PMID- 20127436
TI  - [Chlorambucil treatment of Behcet's syndrome. Retrospective evaluation of two
      cases].
AB  - BACKGROUND: Behcet's syndrome rarely occurs in North America and Central Europe
      (incidence: 1 : 500,000), whereas it is more frequently seen in Japan and
      Mediterranean countries (incidence: 1 : 10,000). The diagnosis is based on the
      detection of symptoms and clinical signs. Orogenital aphthosis, anterior and
      posterior uveitides that frequently cause loss of vision are considered to be
      primary symptoms. Dermatologic manifestations, i.e., erythema nodosum, vascular
      lesions (angio-Behcet's syndrome), gastrointestinal ulcers and neurologic
      involvement, can be observed. HLA B5 is found in some of the patients with
      Behcet's syndrome. Administration of chlorambucil, a cytotoxic compound, is an
      effective form of treatment of symptoms and complications of Behcet's syndrome.
      CASE REPORTS: The present article describes the course of a female and a male
      patient who were 39 and 23 years old when Behcet's syndrome was diagnosed for the
      first time. Treatment with chlorambucil was started in the early 1990s and
      continued for a period of 9 1/2 and 3(3/4) years, respectively, with the symptoms
      remitting during and after this therapy. Approximately 10 years after the start
      of treatment with chlorambucil, the patients' symptoms changed. The female
      patient who was first diagnosed having Behcet's syndrome at the age of 39 years
      developed rheumatoid arthritis with joint destruction. Her symptoms could be
      controlled in the long term by oral administration of prednisone, at doses below
      the Cushing threshold combined with methotrexate. The male patient who was first
      diagnosed having Behcet's syndrome at the age of 23 years developed systemic
      vasculitis remitting during low-dose treatment with prednisone. CONCLUSION:
      Immunosuppressive therapy with chlorambucil administered over several years often
      induces remission of Behcet's syndrome. However, both case reports indicate that
      symptoms can change from Behcet's syndrome to systemic vasculitis or rheumatoid
      arthritis.

PMID- 20127437
TI  - [In Process Citation].

PMID- 20127438
TI  - [Development and implementation of the dementia guideline of the German Society
      of General Practice and Family Medicine].
AB  - The evidence-based guidelines of the German Society of General Practice and
      Family Medicine (DEGAM) are developed according to an established ten-stage plan.
      The twelfth guideline addresses the health care problem of dementia. The main
      focus is the sensitive handling of patients and their relatives, e.g., although
      the goal is an early diagnosis, patients should also be protected against
      overdiagnosis. The treatment of Alzheimer's disease consists of three components:
      optimal care and supervision, the use of nondrug therapy, and a critically
      weighed administration of medications. The successful implementation of the
      guideline should be achieved by a multimodal strategy. This includes not only the
      direct integration of general practitioners (GPs) in developing the guideline,
      but also a comprehensive publication offensive, a wide use in training sessions
      including new media, the testing of complex implementation approaches in trials,
      and the use of the guideline in the context of GP contracts.

PMID- 20127439
TI  - [In Process Citation].

PMID- 20127440
TI  - [In Process Citation].

PMID- 20127441
TI  - [In Process Citation].

PMID- 20127443
TI  - DSM-V: an opportunity to embrace the future of psychiatric diagnosis.

PMID- 20127444
TI  - Women's mental health: a "wish-list" for the DSM V.
AB  - This article highlights four areas of mental health affecting women in the
      reproductive age group which, in the author's opinion, are poorly dealt with in
      the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV)
      (American Psychiatric Association 1994). These are depression occurring during
      pregnancy; childbirth-related post-traumatic stress disorder; disorders of parent
      to-infant attachment and perinatal bereavement. It is suggested that, if these
      could be better addressed in the forthcoming DSM V, this would provide a very
      significant impetus for improved education of health professionals, as well as
      better recognition and earlier intervention in these disorders. As these are
      relatively common disorders, a very large number of women and their families
      would potentially benefit.

PMID- 20127445
TI  - Gender issues and DSM-V.

PMID- 20127446
TI  - DSM-V and reproductive-related psychiatric disorders: a closer look at windows of
      vulnerability.

PMID- 20127447
TI  - DSM-V: toward a gender sensitive approach to psychiatric diagnosis.

PMID- 20127448
TI  - Premenstrual dysphoric disorder: out of the appendix.

PMID- 20127449
TI  - Hormone-specific psychiatric disorders: do they exist?

PMID- 20127450
TI  - Prolonged grief as a distinct disorder, specifically affecting female health.

PMID- 20127451
TI  - Attention-deficit hyperactivity disorder and gender.

PMID- 20127452
TI  - The classification of perinatal mood disorders--suggestions for DSMV and ICD11.

PMID- 20127453
TI  - Postpartum depression: a disorder in search of a definition.

PMID- 20127454
TI  - Classification of mental health disorders in the perinatal period: future
      directions for DSM-V and ICD-11.

PMID- 20127455
TI  - Puerperal psychosis.

PMID- 20127456
TI  - Should childbirth be considered a stressor sufficient to meet the criteria for
      PTSD?

PMID- 20127457
TI  - Isolation, characterization, and evaluation of wild isolates of Lactobacillus
      reuteri from pig feces.
AB  - Lactic acid bacteria (LAB) are a well-used probiotics for health improvements in
      both humans and animals. Despite of several benefits, non-host-specific LAB
      showed poor probiotics effects due to difficulty in colonization and competition
      with normal flora. Therefore, the feasibility of porcine LAB isolates was
      evaluated as a probiotics. Ten of 49 Lactobacillus spp. isolates harbored 2
      approximately 10 kb plasmid DNA. Seven strains were selected based on the safety
      test, such as hemolytic activity, ammonia, indole, and phenylalanine production.
      After safety test, five strains were selected again by several tests, such as
      epithelial adherence, antimicrobial activity, tolerance against acid, bile, heat,
      and cold-drying, and production of acid and hydrogen peroxide. Then, enzyme
      profiles (ZYM test) and antibiotics resistance were analyzed for further
      characterization. Five Lactobacillus reuteri isolates from pig feces were
      selected by safety and functional tests. The plasmid DNA which was able to
      develop vector system was detected in the isolates. Together with these
      approaches, pig-specific Lactobacillus spp. originated from pigs were selected.
      These strains may be useful tools to develop oral delivery system.

PMID- 20127459
TI  - Application of quantitative real-time PCR for enumeration of total bacterial,
      archaeal, and yeast populations in kimchi.
AB  - Kimchi is a Korean traditional fermented food made of brined vegetables, with a
      variety of spices. Various microorganisms are associated with the kimchi
      fermentation process. This study was undertaken in order to apply quantitative
      real-time PCR targeting the 16S and 26S rRNA genes for the investigation of
      dynamics of bacterial, archaeal, and yeast communities during fermentation of
      various types of kimchi. Although the total bacterial and archaeal rRNA gene copy
      numbers increased during kimchi fermentation, the number of yeasts was not
      significantly altered. In 1 ng of bulk DNA, the mean number of rRNA gene copies
      for all strains of bacteria was 5.45 x 10(6) which was 360 and 50 times greater
      than those for archaea and yeast, respectively. The total gene copy number for
      each group of microorganisms differed among the different types of kimchi,
      although the relative ratios among them were similar. The common dominance of
      bacteria in the whole microbial communities of various types of kimchi suggests
      that bacteria play a principal role in the kimchi fermentation process.

PMID- 20127458
TI  - Functional shifts in unvegetated, perhumid, recently-deglaciated soils do not
      correlate with shifts in soil bacterial community composition.
AB  - Past work in recently deglaciated soils demonstrates that microbial communities
      undergo shifts prior to plant colonization. To date, most studies have focused on
      relatively 'long' chronosequences with the ability to sample plant-free sites
      over at least 50 years of development. However, some recently deglaciated soils
      feature rapid plant colonization and questions remain about the relative rate of
      change in the microbial community in the unvegetated soils of these
      chronosequences. Thus, we investigated the forelands of the Mendenhall Glacier
      near Juneau, AK, USA, where plants rapidly establish. We collected unvegetated
      samples representing soils that had been ice-free for 0, 1, 4, and 8 years. Total
      nitrogen (N) ranged from 0.00 approximately 0.14 mg/g soil, soil organic carbon
      pools ranged from 0.6 approximately 2.3 mg/g soil, and both decreased in
      concentration between the 0 and 4 yr soils. Biologically available phosphorus (P)
      and pH underwent similar dynamics. However, both pH and available P increased in
      the 8 yr soils. Nitrogen fixation was nearly undetectable in the most recently
      exposed soils, and increased in the 8 yr soils to approximately 5 ng N
      fixed/cm(2)/h, a trend that was matched by the activity of the soil N-cycling
      enzymes urease and beta-l,4-N-acetyl-glucosa-minidase. 16S rRNA gene clone
      libraries revealed no significant differences between the 0 and 8 yr soils;
      however, 8 yr soils featured the presence of cyanobacteria, a division wholly
      absent from the 0 yr soils. Taken together, our results suggest that microbes are
      consuming allochtonous organic matter sources in the most recently exposed soils.
      Once this carbon source is depleted, a competitive advantage may be ceded to
      microbes not reliant on in situ nutrient sources.

PMID- 20127460
TI  - Arsenite oxidation by a facultative chemolithotrophic bacterium SDB1 isolated
      from mine tailing.
AB  - An arsenite (As[III])-oxidizing bacterium, SDB1, was isolated from mine tailing
      collected from the Sangdong mine area in Korea and showed chemolithotrophic
      growth on As[III] and CO(2) as the respective electron and carbon sources. SDB1
      is Gram-negative, rod-shaped, and belongs to the Sinorhizobium-Ensifer branch of
      alpha-Proteobacteria. Growth and As[III] oxidation was enhanced significantly by
      the presence of yeast extract (0.005%) in minimal salt medium containing 5 mM
      As[III]; decreasing the doubling time from 9.8 to 2.1 h and increasing the As
      [III] oxidation rate from 0.014 to 0.349 pmol As [III] oxidized cell(-1) h(-1).
      As[III] oxidation nearly stopped at pH around 4 and should be performed at pH 7
      approximately 8 to be most effective. SDB1 was immobilized in calcium-alginate
      beads and the oxidation capacity was investigated. Specific As[III] oxidation
      rates obtained with SDB1 (10.1-33.7 mM As[III] oxidized g(-1) dry cell h(-1))
      were 10 approximately 16-times higher than those reported previously with a
      heterotrophic bacterial strain (Simeonova et al., 2005). The stability and
      reusability of immobilized SDB1 strongly suggested that the immobilized SDB1 cell
      System can make the As[III] oxidation process technically and economically
      feasible in practical applications.

PMID- 20127461
TI  - Sphingobacterium bambusae sp. nov., isolated from soil of bamboo plantation.
AB  - A Gram-negative, non-motile, non-spore-forming bacterial strain designated
      IBFC2009(T) was isolated from soil of a bamboo plantation. The strain could grow
      at 11 degrees C approximately 39 degrees C, pH 6.0-9.0, and in the presence of 0
      approximately 5% NaCl. Based on 16S rRNA gene sequence analysis, Strain
      IBFC2009(T) belonged to the genus Sphingobacterium and showed the highest
      sequence similarity of 94.6% (S. composti T5-12(T)) with the type strains within
      the genus. The major fatty acids were summed feature 3 (iso-C(15:0) 2-OH and/or
      C(16:1) omega7c, 34.4%), iso-C(15:0) (22.4%), C(16:0) 3-OH (15.2%), and iso
      C(17:0) 3-OH (12.8%). The G+C content of the genomic DNA was 41.0 mol%. According
      to the phenotypic and genotypic characteristics, Strain IBFC2009(T) should
      represent a novel species of the genus Sphingobacterium, for which the name
      Sphingobacterium bambusae sp. nov. is proposed. The type strain is IBFC2009(T)
      (=CCTCC AB 209162(T) =KCTC 22814(T)).

PMID- 20127462
TI  - Paenibacillus pini sp. nov., a cellulolytic bacterium isolated from the
      rhizosphere of pine tree.
AB  - Strain S22(T), a novel cellulolytic bacterium was isolated from the rhizosphere
      of pine trees. This isolate was Gram-reaction positive, motile and rods, and
      formed terminal or subterminal ellipsoidal spores. S22(T) represented positive
      activity for catalase, oxidase, esterase (C4), esterase lipase (C8), beta
      galactosidase, leucine arylamidase, and hydrolysis of esculin. It contained meso
      diaminopimelic acid as the diagnostic dia-mino acid in the cell-wall. The
      predominant isoprenoid quinone was menaquinone 7 (MK-7), and the major cellular
      fatty acids were anteiso-C(15:0) (52.9%), iso-Ci(16:0) (11.3%), and iso-C(15:0)
      (10.0%). The DNA G+C content was 43.3 mol%. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that this isolate belonged to the family
      Paenibacillaceae. S22(T) exhibited less than 97.0% 16S rRNA gene similarity with
      all relative type strains in the genus Paenibacillus, and the most closely
      related strains were Paenibacillus anaericanus MH21(T) and Paenibacillus
      ginsengisoli Gsoil 1638(T), with equal similarities of 95.8%. This polyphasic
      evidence suggested that strain S22(T) should be considered a novel species in the
      genus Paenibacillus, for which the name, Paenibacillus pini sp. nov., is
      proposed. The type strain is S22(T) (=KCTC 13694(T) =KACC 14198(T) =JCM
      16418(T)).

PMID- 20127463
TI  - Virgibacillus xinjiangensis sp. nov., isolated from a Salt Lake of Xin-jiang
      Province in China.
AB  - A strictly aerobic Gram-positive, moderately halophilic spore forming bacterium,
      designated strain SL6-1(T), was isolated from a salt lake in Xin-jiang province,
      China. Growth of strain SL6-1(T) was observed at NaCl concentrations of 0
      approximately 20% (w/v) (the optimum being 5 approximately 7%, w/v). The
      peptidoglycan type of strain SL6-1(T) was Algamma-meso-diaminopimelic acid and
      its major cellular fatty acids were iso-C(14:0) and iso-C(16:0) and ante-iso
      C(15:0). The major respiratory isoprenoid quinone was MK-7 and the G+C content of
      the genomic DNA was 44.5 mol%. The major cellular phospholipids were
      phosphatidylglycerol and diphosphatidylglycerol. Phylogenetic analysis based on
      16S rRNA gene sequences showed that strain SL6-1(T) formed a phylogenetic lineage
      within the genus Virgibacillus. Based on 16S rRNA gene sequence similarity, the
      strain was most closely related to Virgibacillus olivae E(30)8(T), Virgibacillus
      kekensis YIM kkny16(T), Virgibacillus marismortui DSM 12325(T) with 97.1%, 97.1%,
      and 97.0% gene sequence similarities, respectively and the sequence similarities
      to other related taxa were less than 96.7%. The DNA relatedness values between
      strain SL6-1(T) and V. olivae E(30)8(T), V. kekensis YIM kkny16(T), V.
      marismortui DSM 12325(T) were 16.7%, 51.0%, and 22.8%, respectively. On the basis
      of physiological, biochemical and phylogenetic properties, strain SL6-1(T)
      represents a novel species, for which the name Virgibacillus xinjiangensis sp.
      nov. is proposed. The type strain is SL6-1(T) (=KCTC 13128(T) =DSM 19031(T)).

PMID- 20127465
TI  - Methylobacterium dankookense sp. nov., isolated from drinking water.
AB  - A pink-pigmented bacterium, designated SW08-7(T) was isolated from the drinking
      water of a water purifier. Cells were Gram-negative, rod-shaped, strictly
      aerobic, and non-spore-forming. It grew optimally at 25 degrees C, pH 6
      approximately 7. Phylogenese analysis based on 16S rRNA gene sequence showed that
      strain SW08-7(T) belongs to the genus Methylobacterium. The highest 16S rRNA gene
      sequence similarities were found to Methylobacterium mesophilicum JCM 2829(T)
      (96.9%), Methylobacterium brachiatum B0021(T) (96.9%), Methylobacterium
      phyllosphaerae CBMB27(T) (96.6%), Methylobacterium radiotolerans JCM 2831(T)
      (96.6%), and Methylobacterium hispanicum GP34(T) (96.5%). DNA-DNA hybridization
      experiment revealed low-level (28.5%) of DNA-DNA relatedness between strain SW08
      7(T) and Methylobacterium hispanicum. The genomic DNA G+C content was 68.9 mol%
      and the major isoprenoid quinone was Q-10. The major cellular fatty acid of
      strain SW08-7(T) was C(18:1) omega7c (79.8+/-2.1%). Results of phylogenetic,
      phenotypic, and biochemical analyses revealed that strain SW08-7(T) could be
      classified as representing a novel species of genus Methylobacterium, for which
      the name Methylobacterium dankookense sp. nov. is proposed. The type strain is
      SW08-7(T) (=KCTC 22512(T) =DSM 22415(1)).

PMID- 20127464
TI  - Scopulibacillus darangshiensis gen. nov., sp. nov., isolated from rock.
AB  - A novel, Gram-positive bacterium, designated DLS-06(T), was isolated from scoria
      (volcanic ash) under rock on the peak of small mountain (300 m above the sea
      level; known as Darangshi Oreum) in Jeju, Republic of Korea. The cells of the
      isolate were aerobic, oxidase-negative, catalase-positive, endospore-forming, non
      motile rods. The organism grew at 25 approximately 30 degrees C and initial pH
      6.1 approximately 9.1. A neighbour-joining tree based on 16S rRNA gene sequences
      showed that the organism was related to members of the family
      "Sporolactobacillaceae" and related taxa. The phylogenetic neighbours were
      Pullulanibacillus naganoensis (95.2% 16S rRNA gene sequence similarity),
      Tuberibacillus calidus (95.0%) and Sporolactobacillus (91.8 approximately 94.2%).
      Levels of 16S rRNA gene sequence similarity of the isolate to representatives of
      other genera were in the range of 87.2 approximately 93.7%. The organism
      contained meso-diaminopimelic acid as the diagnostic diamino acid in the cell
      wall peptidoglycan. The predominant menaquinone was MK-7. The polar lipid profile
      contained diphosphatidylglycerol, phosphatidylglycerol, an unknown ninhydrin
      positive phospholipid, three unknown phospholipids and an unknown lipid. The
      major fatty acids were anteiso-C(15:0) and anteiso-C(17:0). The G+C content of
      the DNA was 50.8 mol%. On the basis of the phenotypic and phylogenetic data
      presented in this study, this organism represents a novel genus and species in
      the order Bacillales, for which the name Scopulibacillus darangshiensis gen.
      nov., sp. nov. is proposed. The type strain is DLS-06(T) (=DSM 19377(T) =KCTC
      13161(T)).

PMID- 20127466
TI  - Symbiotic relationship between Microbacterium sp. SK0812 and Candida tropicalis
      SK090404.
AB  - A bacterium growing inside yeast cytoplasm was observed by light microscope
      without staining. The bacterium was separately stained from yeast cell by a
      fluorescent dye, 4',6-diamidino-2-phenylindole (DAPI). The bacterium actively
      moved inside yeast cytoplasm and propagated in company with the yeast growth. The
      bacterium was separated from the yeast cytoplasm by selective disruption of yeast
      cells and the yeast without the intracellular bacterium (YWOB) was obtained by
      selective inactivation of bacterial cells. The yeast and the intracellular
      bacterium were identified as Candida tropicalis and Microbacterium sp.,
      respectively. The length of Microbacterium sp. and C. tropicalis measured with
      SEM image was smaller than 0.5 microm and was larger than 5 microm, respectively.
      The yeast with the intracellular bacterium (YWIB) grew in a starch-based medium
      but the YWOB was not C. tropicalis has neither extracellular nor intracellular
      saccharification enzyme. Glucose was produced from starch by the extracellular
      crude enzyme (culture fluid) of Microbacterium sp. YWIB produced significantly
      more ethanol from glucose than YWOB but did not from starch. Conclusively, C.
      tropicalis is thought to catabolize starch dependent upon Microbacterium sp.
      growing in its cytoplasm and furnish stable habitat for the Microbacterium sp.

PMID- 20127467
TI  - Proteomic analysis of Acinetobacter baumannii in biofilm and planktonic growth
      mode.
AB  - Recently, multidrug-resistant clinical isolates of Acinetobacter baumannii have
      been found to have a high capacity to form biofilm. It is well known that
      bacterial cells within biofilms are highly resistant to antibiotics, UV light,
      acid exposure, dehydration, and phagocytosis in comparison to their planktonic
      counterparts, which suggests that the cells in a biofilm have altered metabolic
      activity. To determine which proteins are up-regulated in A. baumannii biofilm
      cells, we performed a proteomic analysis. A clinical isolate of A. baumannii 1656
      2, which was characterized to have a high biofilm forming ability, was cultivated
      under biofilm and planktonic conditions. Outer membrane enriched A. baumannii
      1656-2 proteins were separated by two-dimensional (2-D) gel electrophoresis and
      the differentially expressed proteins were identified by MALDI-TOF mass
      spectrometry. The proteins up-regulated or expressed only in biofilm cells of A.
      baumannii are categorized as follows: (i) proteins processing environmental
      information such as the outer membrane receptor protein involved in mostly Fe
      transport, a sensor histidine kinase/response regulator, and diguanylate cyclase
      (PAS-GGEDF-EAL domain); (ii) proteins involved in metabolism such as NAD-linked
      malate dehydrogenase, nucleoside-diphosphate sugar epimerase, putative GalE,
      ProFAR isomerase, and N-acetylmuramoyl-L: -alanine amidase; (iii) bacterial
      antibiotic resistance related proteins; and (iv) proteins related to gene repair
      such as exodeoxyribonuclease III and GidA. This proteomic analysis provides a
      fundamental platform for further studies to reveal the role of biofilm in the
      persistence and tolerance of A. baumannii.

PMID- 20127468
TI  - Functional characterization of the copper-transporting P-type ATPase gene of
      Penicillium janthinellum strain GXCR.
AB  - Copper (Cu)-transporting P-type ATPase (CTPA) genes have been documented to play
      an important role in resistance to heavy metals. However, our understanding of
      roles of CTPA genes of the filamentous fungi was based only on sequence
      similarity prediction before. In a previous study, we isolated a Penicillum
      janthinellum strain GXCR of higher tolerance to Cu (200 mM). In this study, we
      cloned the partial cDNA of CTPA gene, named PcpA, from the strain GXCR. Sequence
      alignment indicated that the cloned cDNA sequence has the highest identity
      (94.4%) with a predictive CTPA gene of Aspergillus clavatus. The PcpA-encoded
      protein, termed PcpA, has classical functional domains of CTPAs, and shows
      differences from reported CTPAs in some specific sequence motifs and
      transmembrane regions. Expression of the PcpA was induced by extracellular Cu,
      cadmium (Cd), and silver (Ag). PcpA RNA interference (RNAi) mutants with a
      reduced level of PcpA mRNA were more sensitive to Cu, iron, Cd, and Ag than the
      wild-type (WT) strain GXCR. When grown in the presence of Cu, iron, and Cd,
      intracellular Cu and iron contents in the PcpA RNAi mutant were significantly
      (P<0.05) lower than those in the WT; However, intracellular Cd content in the
      mutant was significantly (P<0.05) higher than that in the WT. Taken together, it
      can be concluded that the PcpA functions in Cu uptake and homeostasis, iron
      uptake, and Cd export from the cytosol to the extracytosol.

PMID- 20127469
TI  - Hepatitis B virus core interacts with the host cell nucleolar protein,
      nucleophosmin 1.
AB  - Hepatitis B virus (HBV) genome replication requires the packaging of viral
      factors (pregenomic RNA and polymerase) as well as host factors, including heat
      shock proteins and protein kinase C. Previous reports have suggested that there
      are several unidentified host factors that affect this encapsidation step. In
      this study, we identified a new host factor, nucleophosmin (B23) that interacts
      with the HBV core protein 149 (Cpl49). We analyzed this factor using NHS
      activated sepharose resin and MALDI-TOF MS. Using the BIAcore analysis system, we
      were also able to deduce that the B23.1 residues 259-294 were required for the
      interaction between Cpl49 and B23.1 in vitro.

PMID- 20127470
TI  - Analysis of a novel class 1 integron containing metallo-beta-lactamase gene VIM-2
      in Pseudomonas aeruginosa.
AB  - Carbapenems such as imipenem are stable to most beta-lactamases. Recently,
      increased numbers of carbapenemase producing Gram-negative bacterial strains have
      been isolated because of the increased use of cabapenems. In this respect,
      control of these infectious carbapenemase producing Gram-negative bacteria and
      understanding their resistance mechanism are becoming more important. These
      carbapenem-hydrolyzing beta-lactamase genes have been reported to exist mostly as
      gene cassettes in an integron. This implies that antibiotic resistance genes may
      be transferred to other bacteria via the integron. In the present study, we
      identified and analyzed an integron containing VIM-2 type metallo-beta-lactamase
      gene in a carbapenemase producing Pseudomonas aeruginosa. In addition, the
      possibility of resistance spread by integron located in a plasmid was tested.
      Among glucose non-fermenting Gram-negative bacilli with reduced imipenem
      susceptibility (MIC > or = 8 microg/ml) isolated from Korean patients, P.
      aeruginosa 1082 showed resistance to most beta-lactams, cephalosporin, and
      aminoglycoside. We found that P. aeruginosa 1082 was inhibited by EDTA in EDTA
      double disk synergy test which means that this strain produces metallo-beta
      lactamase. Class 1 integron containing bla (VIM-2) (carbapenem resistance gene),
      qacF (quaternary ammonium compound resistance gene), aacA4 (aminoglycoside
      resistance gene), catB3 (chloramphenicol resistance gene), bla (oxa-30) (extended
      spectrum beta-lactam resistance gene), and aadAl (aminoglycoside resistance gene)
      gene cassettes was detected in P. aeruginosa 1082. The size of the integron was
      5,246 bp and the structure and arrangement of the integron was a novel one in
      comparison with other integrons found in other P. aeruginosa. The integron could
      be transferred to Escherichia coli JM109 from P. aeruginosa 1082 possibly via
      self-transferable plasmid DNA. The integron and a bla (VIM-2) gene were detected
      in the plasmid DNA of the transconjugants whose imipenem resistance was slightly
      increased as a result of accepting the integron from the donor strain.

PMID- 20127471
TI  - Effects of methyl gallate and gallic acid on the production of inflammatory
      mediators interleukin-6 and interleukin-8 by oral epithelial cells stimulated
      with Fusobacterium nucleatum.
AB  - Interactions between periodontal bacteria and human oral epithelial cells can
      lead to the activation and expression of a variety of inflammatory mediators in
      epithelial cells. Fusobacterium nucleatum is a filamentous human pathogen that is
      strongly associated with periodontal diseases. This study examined the effects of
      methyl gallate (MG) and gallic acid (GA) on the production of inflammatory
      mediators, interleukin (IL)-6 and IL-8, by oral epithelial cells stimulated by F.
      nucleatum. In a real-time reverse transcription-polymerase chain reaction and an
      enzyme-linked immunosorbent assay, live F. nucleatum induced high levels of gene
      expression and protein release of IL-6 and IL-8. The effects of MG and GA were
      examined by treating KB oral epithelial cells with MG and GA and stimulating them
      with F. nucleatum. MG and GA inhibited significantly the increases in the IL-6
      and IL-8 gene and protein levels in a dose-dependent manner. These Compounds also
      inhibited the growth of F. nucleatum. No visible effects of MG and GA on the
      adhesion and invasion of KB cells by F. nucleatum were observed. In conclusion,
      both MG and GA inhibit IL-6 and IL-8 production from F. nucleatum-activated KB
      cells.

PMID- 20127472
TI  - Characterization of a spontaneous avirulent mutant of Legionella pneumophila
      Serogroup 6: evidence of DotA and flagellin involvement in the loss of virulence.
AB  - The pathogenesis of Legionella pneumophila mainly resides in its ability to
      inhibit the phagosome-lysosome fusion, which normally prevents the killing of the
      host cells. In order to characterize the molecular alterations that occurred in a
      spontaneous avirulent mutant of Legionella pneumophila serogroup 6, named Vir-,
      we investigated the ability of the mutant to adhere to and multiply in the
      WI26VA4 alveolar epithelial cell line and in human macrophages, when compared to
      its parental strain, Vir+. We also determined the colocalization of bacteria with
      LAMP-1 to gain an insight into the phagosome-lysosome fusion process.
      Additionally, we determined the flagellin expression and dotA nucleotide
      sequencing. We observed a lack of expression of flagellin and an in-frame
      mutation in the dotA. gene. The data obtained strongly suggest the loss of
      virulence of the mutant could probably be due to the absence of flagellin and the
      dysfunctional type IV secretion System, resulting from the DotA protein being
      severely compromised.

PMID- 20127473
TI  - Biochemical characteristics of immune-associated phospholipase A(2) and its
      inhibition by an entomopathogenic bacterium, Xenorhabdus nematophila.
AB  - An entomopathogenic bacterium, Xenorhabdus nematophila, induces an
      immunosuppression of target insects by inhibiting phospholipase A(2) (PLA(2))
      activity. Recently, an immune-associated PLA(2) gene was identified from the red
      flour beetle, Tribolium castaneum. This study cloned this PLA(2) gene in a
      bacterial expression vector to produce a recombinant enzyme. The recombinant T.
      castaneum PLA(2) (TcPLA(2)) exhibited its characteristic enzyme activity with
      substrate concentration, pH, and ambient temperature. Its biochemical
      characteristics matched to a secretory type of PLA(2) (sPLA(2)) because its
      activity was inhibited by dithiothreitol (a reducing agent of disulfide bond) and
      bromophenacyl bromide (a specific sPLA(2) inhibitor) but not by methylarachidonyl
      fluorophosphonate (a specific cytosolic type of PLA(2)). The X. nematophila
      culture broth contained PLA(2) inhibitory factor(s), which was most abundant in
      the media obtained at a stationary bacterial growth phase. The PLA(2) inhibitory
      factor(s) was heat-resistant and extracted in both aqueous and organic fractions.
      Effect of a PLA(2)-inhibitory fraction on the immunosuppression of T. castaneum
      was equally comparable with that resulted from inhibition of the TcPLA(2) gene
      expression by RNA interference.

PMID- 20127474
TI  - Classification of hybrid and altered Vibrio cholerae strains by CTX prophage and
      RS1 element structure.
AB  - Analysis of the CTX prophage and RS1 element in hybrid and altered Vibrio cholera
      O1 strains showed two classifiable groups. Group I strains contain a tandem
      repeat of classical CTX prophage on the small chromosome. Strains in this group
      either contain no element(s) or an additional CTX prophage or RS1 element(s) on
      the large chromosome. Group II strains harbor RS1 and CTX prophage, which has an
      E1 Tor type rstR and classical ctxB on the large chromosome.

PMID- 20127475
TI  - Generation of expression vectors for high-throughput functional analysis of
      target genes in Schizosaccharomyces pombe.
AB  - An immediate challenge in the post-genomic era is to assign a biological
      functions to proteins unraveled by genome analysis. This report is based on
      studies conducted using Schizosaccharomyces pombe, a simple model organism, and
      presents various vector systems as tools for high-throughput functional analysis
      of human genes. We constructed S. pombe expression vectors for efficient cloning
      of genes via the Gateway system. We modified the pREP and pSLF series vectors,
      which are widely used for gene expression in S. pombe. The vectors constructed
      have a uniform backbone of S. pombe autonomously replicating sequence (ARS)
      elements with different selective markers, namely, urw4 (+) and Saccharomyces
      cerevisiae LEU2 complementing leul. These vectors contain 3 different strengths
      of the inducible promoter nmtl, which affect the expression levels of the cloned
      open reading frames (ORFs). Further, target proteins can be fused with an N
      terminal or C-terminal tag such as triple hemagglutinin (3x HA), enhanced green
      fluorescent protein (EGFP), or Discosoma red fluorescent protein (DsRed). We
      tested the feasibility of the constructed vectors by using 3 human genes, namely,
      RAB18, SCC-112, and PTEN. Proper expression of tagged RAB18 was confirmed by
      western blot analysis. Further, localization of RAB18, SCC112, and PTEN was
      demonstrated. The constructed vectors can be utilized for high-throughput
      functional analysis of heterologous genes.

PMID- 20127476
TI  - Characterization of plasmid pSY3 in Sphingobium chungbukense DJ77.
AB  - This study determined the complete nucleotide sequence of the plasmid pSY3 from
      Sphingobium chungbukense DJ77. It was 35,735 bp long with a G+C content of 61.9%.
      Forty open reading frames (ORFs) were found. We predicted these ORFs would encode
      proteins associated with plasmid replication, conjugative transfer, transposition
      of genes, plasmid stability/partition, hypothetical protein, and some other
      functions. Genes for biodegradation were not found. No other plasmid homologous
      to pSY3 in the overall nucleotide sequence or gene organization could be found in
      the NCBI database.

PMID- 20127479
TI  - Comparative antioxidant profiling of tolerant and sensitive varieties of Brassica
      juncea L. to arsenate and arsenite exposure.
AB  - Comparative antioxidant profiling of tolerant (TPM-1) and sensitive (TM-4)
      variety of Brassica juncea L. was performed after exposure to arsenate [As(V)]
      and arsenite [As(III)]. TPM-1 demonstrated higher accumulation of As upon
      exposure to both 500 microM As(V) and 250 microM As(III) (49 and 37 microg g(-1)
      dw after 15 days) as compared with that observed in TM-4. The activities of
      various antioxidant enzymes and the level of glutathione and proline
      demonstrated, in general, a comparatively better response in TPM-1 than in TM-4
      that presumably allowed TPM-1 to tolerate higher As concentrations as compared
      with that of TM-4.

PMID- 20127480
TI  - An overview of in silico protein function prediction.
AB  - As the protein databases continue to expand at an exponential rate, fed by daily
      uploads from multiple large scale genomic and metagenomic projects, the problem
      of assigning a function to each new protein has become the focus of significant
      research interest in recent times. Herein, we review the most recent advances in
      the field of automated function prediction (AFP). We begin by defining what is
      meant by biological "function" and the means of describing such functions using
      standardised machine readable ontologies. We then focus on the various function
      prediction programs available, both sequence and structure based, and outline
      their associated strengths and weaknesses. Finally, we conclude with a brief
      overview of the future challenges and outstanding questions in the field, which
      still remain unanswered.

PMID- 20127478
TI  - Dynamin 2 and human diseases.
AB  - Dynamin 2 (DNM2) mutations cause autosomal dominant centronuclear myopathy, a
      rare form of congenital myopathy, and intermediate and axonal forms of Charcot
      Marie-Tooth disease, a peripheral neuropathy. DNM2 is a large GTPase mainly
      involved in membrane trafficking through its function in the formation and
      release of nascent vesicles from biological membranes. DNM2 participates in
      clathrin-dependent and clathrin-independent endocytosis and intracellular
      membrane trafficking (from endosomes and Golgi apparatus). Recent studies have
      also implicated DNM2 in exocytosis. DNM2 belongs to the machinery responsible for
      the formation of vesicles and regulates the cytoskeleton providing intracellular
      vesicle transport. In addition, DNM2 tightly interacts with and is involved in
      the regulation of actin and microtubule networks, independent from membrane
      trafficking processes. We summarize here the molecular, biochemical, and
      functional data on DNM2 and discuss the possible pathophysiological mechanisms
      via which DNM2 mutations can lead to two distinct neuromuscular disorders.

PMID- 20127481
TI  - Assessment of the effects of the pesticide imidacloprid on the behaviour of the
      aquatic oligochaete Lumbriculus variegatus.
AB  - Contaminants, such as pesticides, can cause direct toxic effects when released
      into aquatic environments. Suitably sensitive species can help us understand and
      predict the impacts of such pollutants. Automated sediment toxicity testing and
      biomonitoring has grown rapidly, and biomonitoring instruments have proven
      appropriate for studying the effects of pollutants. A new approach in online
      biomonitoring, using the multispecies freshwater biomonitor was developed in the
      present study, using whole-sediment toxicity tests and behavioural responses of
      the freshwater oligochaete Lumbriculus variegatus. Endpoints, such as mortality
      and growth, were used to study the effects of the pesticide imidacloprid and to
      achieve a gradient of responses; exposures to contaminated sediments were
      performed over 10 days' duration (short-term tests). High mortality was observed
      in the three highest concentrations of imidacloprid, and inhibition of behaviour
      was monitored along a gradient of pesticide concentration. Exposure to
      imidacloprid-contaminated sediments affected growth, behaviour, and avoidance in
      L. variegatus.

PMID- 20127482
TI  - Uranium exposure to the tropical duckweed Lemna aequinoctialis and pulmonate
      snail Amerianna cumingi: fate and toxicity.
AB  - The discharge of catchment-management water from the Ranger uranium (U) mine into
      Magela Creek upstream of the Ramsar-listed Magela Floodplain in Kakadu National
      Park is an important part of the mine's water-management system. Because U is one
      of the primary toxicants associated with this water, a receiving-water trigger
      value (TV), based on chronic toxicity data from five local native species, was
      derived for U. To strengthen the data set underpinning the derivation of the TV,
      the chronic toxicity of U to two additional tropical freshwater species, duckweed
      Lemna aequinoctialis (96-hour growth rate), and pulmonate gastropod, Amerianna
      cumingi (96-hour reproduction), was determined. The fate of U within the test
      systems was an important component of the study because analysis of U
      concentrations during the snail tests indicated that a substantial proportion of
      U (approximately 25%) was being lost from the test solutions when integrated
      during the entire test duration. Analysis of the snails and their food for U
      indicated that only a small proportion that was lost from solution was being
      taken up by the snails. Therefore, the majority of U that was lost was considered
      unavailable to the snails, and thus the exposure concentrations used to calculate
      the toxicity estimates were adjusted downward. Integrating the loss of U from the
      L. aequinoctialis test solutions over time showed that only a small proportion
      (6% to 13%) was lost during the test: Of that, almost half (2-5%) was taken up by
      the plants (constituting exposure). Uranium was only moderately toxic to L.
      aequinoctialis, with no observed-effect concentrations, lowest observed-effect
      concentrations, and inhibition concentrations causing 10% and 50% effects (IC10
      and IC50) values of 226, 404, 207, and 1435 microg/l, respectively. A. cumingi
      was found to be more sensitive to U than L. aequinoctialis, with NOEC, LOEC,
      IC10, and IC50 values of 60, 61, 15, and 278 microg/l, respectively. The data for
      these two additional species will be used to revise the current TV for U in
      Magela Creek.

PMID- 20127483
TI  - Comment on Oguz et al.: A new classification and guide for surgical treatment of
      spinal tuberculosis.

PMID- 20127484
TI  - Abnormal fatty acid distribution of the serum phospholipids of patients with non
      Hodgkin lymphoma.
AB  - The data about the fatty acid (FA) status of non-Hodgkin lymphoma (NHL) patients
      are poor. Therefore, the aim of this study was to investigate the FA profile of
      serum phospholipids in NHL patients related to the aggressiveness and clinical
      stage of NHL. We analyzed the FA profile of serum phospholipids in 47 newly
      diagnosed, untreated NHL patients and in 29 healthy subjects. Significantly
      higher (p < 0.001) levels of palmitic (16:0), oleic (18:1 n-9) and arachidonic
      acids (20:4 n-6), saturated and monounsaturated FA were found in NHL patients,
      while linoleic acid (18:2 n-6) and the levels of total polyunsaturated FA (PUFA),
      n-3 PUFA, eicosapentaenoic (20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) were
      significantly reduced (p < 0.01). The level of oleic acid in patients with
      indolent NHL was significantly lower (p < 0.05) than in more aggressive types of
      disease. Contents of palmitoleic acid, docosatetraenoic (22:4 n-6), and PUFA was
      lower in very aggressive NHL. According to clinical stage (CS), patients with CS
      I had significantly higher SFA and lower n-6 FA than other three groups, and
      group with CS IV showed significantly decreased DHA and n-3 PUFA. Our results
      showed an abnormal FA profile in serum phospholipids in NHL patients.

PMID- 20127485
TI  - Th17 cytokines and arthritis.
AB  - Th17 cells are implicated in human autoimmune diseases, such as rheumatoid
      arthritis (RA), although it has not been established whether this persistent
      destructive arthritis is driven by Th1 and/or Th17 cells. Interleukin-17A (IL
      17A) contributes to the pathogenesis of arthritis as has been shown in several
      experimental arthritis models. Importantly, recent data from first clinical
      trials with anti-IL-17A antibody treatment in psoriatic arthritis patients and RA
      patients looks promising. This review summarizes the findings about the role of
      Th17 cells in arthritis and discusses the impact of the different Th17 cytokines
      in the pathogenesis of this disease. However, further studies are needed to
      unravel the interplay between IL-17A and other Th17 cytokines such as IL-17F, IL
      22, and IL-21 in the pathoimmunological process of this crippling disease, in
      particular, whether regulating Th17 cell activity or specific combinations of
      Th17 cytokines will have additional value compared to neutralizing IL-17A
      activity alone. Moreover, tumor necrosis factor-positive Th17 cells are discussed
      as potential dangerous cells in driving persistent arthritis in human early RA.

PMID- 20127486
TI  - Genetic resistance to diet-induced obesity in chromosome substitution strains of
      mice.
AB  - Discovery of genes that confer resistance to diseases such as diet-induced
      obesity could have tremendous therapeutic impact. We previously demonstrated that
      the C57BL/6J-Chr(A/J)/NaJ panel of chromosome substitution strains (CSSs) is a
      unique model for studying resistance to diet-induced obesity. In the present
      study, three replicate CSS surveys showed remarkable consistency, with 13 A/J
      derived chromosomes reproducibly conferring resistance to high-fat-diet-induced
      obesity. Twenty CSS intercrosses, one derived from each of the 19 autosomes and
      chromosome X, were used to determine the number and location of quantitative
      trait loci (QTLs) on individual chromosomes and localized six QTLs. However,
      analyses of mean body weight in intercross progeny versus C57BL/6J provided
      strong evidence that many QTLs discovered in the CSS surveys eluded detection in
      these CSS intercrosses. Studies of the temporal effects of these QTLs suggest
      that obesity resistance was dynamic, with QTLs acting at different ages or after
      different durations of diet exposure. Thus, these studies provide insight into
      the genetic architecture of complex traits such as resistance to diet-induced
      obesity in the C57BL/6J-Chr(A/J)/NaJ CSSs. Because some of the QTLs detected in
      the CSS intercrosses were not detected using a traditional C57BL/6J x A/J
      intercross, our results demonstrate that surveys of CSSs and congenic strains
      derived from them are useful complementary tools for analyzing complex traits.

PMID- 20127487
TI  - Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large
      deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope
      disruption.
AB  - Major nuclear envelope abnormalities, such as disruption and/or presence of
      intranuclear organelles, have rarely been described in cardiomyocytes from
      dilated cardiomyopathy (DCM) patients. In this study, we screened a series of 25
      unrelated DCM patient samples for (a) cardiomyocyte nuclear abnormalities and (b)
      mutations in LMNA and TMPO as they are two DCM-causing genes that encode proteins
      involved in maintaining nuclear envelope architecture. Among the 25 heart samples
      investigated, we identified major cardiomyocyte nuclear abnormalities in 8
      patients. Direct sequencing allowed the detection of three heterozygous LMNA
      mutations (p.D192G, p.Q353K and p.R541S) in three patients. By multiplex ligation
      dependant probe amplification (MLPA)/quantitative real-time PCR, we found a
      heterozygous deletion encompassing exons 3-12 of the LMNA gene in one patient.
      Immunostaining demonstrated that this deletion led to a decrease in lamin A/C
      expression in cardiomyocytes from this patient. This LMNA deletion as well as the
      p.D192G mutation was found in patients displaying major cardiomyocyte nuclear
      envelope abnormalities, while the p.Q353K and p.R541S mutations were found in
      patients without specific nuclear envelope abnormalities. None of the DCM
      patients included in the study carried a mutation in the TMPO gene. Taken
      together, we found no evidence of a genotype-phenotype relationship between the
      onset and the severity of DCM, the presence of nuclear abnormalities and the
      presence or absence of LMNA mutations. We demonstrated that a large deletion in
      LMNA associated with reduced levels of the protein in the nuclear envelope
      suggesting a haploinsufficiency mechanism can lead to cardiomyocyte nuclear
      envelope disruption and thus underlie the pathogenesis of DCM.

PMID- 20127488
TI  - Reverse rate-dependent changes are determined by baseline action potential
      duration in mammalian and human ventricular preparations.
AB  - Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the
      action potential duration (APD). In spite of the several theories developed so
      far to explain this reverse rate-dependency (RRD), its mechanism has not yet been
      clarified. The aim of the present work was to further elucidate the mechanisms
      responsible for RRD in mammalian ventricular myocardium. Action potentials were
      recorded using conventional sharp microelectrodes from human, canine, rabbit and
      guinea pig ventricular myocardium in a rate-dependent manner varying the cycle
      length (CL) between 0.3 and 5 s. Rate-dependent drug effects were studied using
      agents known to lengthen or shorten action potentials, and these drug-induced
      changes in APD were correlated with baseline APD values. Both drug-induced
      lengthening (by dofetilide, sotalol, E-4031, BaCl(2), veratrine, BAY K 8644) and
      shortening (by mexiletine, tetrodotoxin, lemakalim) of action potentials
      displayed RRD, i.e., changes in APD were greater at longer than at shorter CLs.
      In rabbit, where APD is a biphasic function of CL, the drug-induced APD changes
      were proportional to baseline APD values but not to CL. Similar results were
      obtained when repolarization was modified by injection of inward or outward
      current pulses in isolated canine cardiomyocytes. In each case the change in APD
      was proportional to baseline APD (i.e., that measured before the superfusion of
      drug or injection of current). Also, the net membrane current (I (net)),
      determined from the action potential waveform at the middle of the plateau, was
      inversely proportional to APD and consequently with to CL. The results indicate
      that RRD is a common characteristic of all the drugs tested regardless of the
      modified ion current species. Thus, drug-induced RRD can be considered as an
      intrinsic property of cardiac membranes based on the inverse relationship between
      I (net) and APD.

PMID- 20127489
TI  - Thalamic volumes in patients with bipolar disorder.
AB  - There are several hypotheses on functional neuronal networks that modulate mood
      states and which might form the neuroanatomical basis of bipolar disorder. The
      thalamus has been reported to be a key structure within the circuits that
      modulate mood states and might thus play an important role within the aetiology
      of the bipolar affective disorder. Nevertheless, structural brain imaging studies
      on the thalamus volume of bipolar patients have shown heterogeneous results.
      Using structural MRI scanning, we compared the thalamus volume of 41 euthymic
      bipolar patients to the thalamus volume of 41 well-matched healthy controls.
      Taking the concomitant medication as a co-variable within the patient group, the
      analysis of variance revealed a significantly smaller relative volume of the
      right thalamus in patients not treated with lithium when compared with healthy
      controls. In contrast, there are no significant differences concerning the
      thalamus volume between all euthymic bipolar patients and healthy controls. The
      study only shows findings of a transverse section. No longitudinal analysis was
      performed. More detailed information on patients' pharmacological histories could
      not be obtained. In conclusion, this result may be interpreted as an indication
      of the impact of the thalamus in the pathogenesis of the bipolar I disorder and
      emphasises the need for further longitudinal studies in bipolar patients with
      special attention paid to the concomitant medication, in particular to the role
      of lithium.

PMID- 20127490
TI  - Spatio-temporal changes of SDF1 and its CXCR4 receptor in the dorsal root ganglia
      following unilateral sciatic nerve injury as a model of neuropathic pain.
AB  - There is a growing evidence that chemokines and their receptors play a role in
      inducing and maintaining neuropathic pain. In the present study, unilateral
      chronic constriction injury (CCI) of rat sciatic nerve under aseptic conditions
      was used to investigate changes for stromal derived factor-1 (SDF1) and its CXCR4
      receptor in lumbal (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) from
      both sides of naive, CCI-operated and sham-operated rats. All CCI-operated rats
      displayed mechanical allodynia and thermal hyperalgesia in hind paws ipsilateral
      to CCI, but forepaws exhibited only temporal changes of sensitivity not
      correlated with alterations in SDF1 and CXCR4 proteins. Naive DRG displayed
      immunofluorescence for SDF1 (SDF1-IF) in the satellite glial cells (SGC) and
      CXCR4-IF in the neuronal bodies with highest intensity in small- and medium-sized
      neurons. Immunofluorescence staining and Western blot analysis confirmed that
      unilateral CCI induced bilateral alterations of SDF1 and CXCR4 proteins in both
      L4-L5 and C7-C8 DRG. Only lumbal DRG were invaded by ED-1+ macrophages exhibiting
      SDF1-IF while elevation of CXCR4-IF was found in DRG neurons and SGC but not in
      ED-1+ macrophages. No attenuation of mechanical allodynia, but reversed thermal
      hyperalgesia, in ipsi- and contralateral hind paws was found in CCI-operated rats
      after i.p. administration of CXCR4 antagonist (AMD3100). These results indicate
      that SDF1/CXCR4 changes are not limited to DRG associated with injured nerve but
      that they also spread to DRG non-associated with such nerve. Functional
      involvement of these alterations in DRG non-associated with injured nerve in
      neuropathic pain remains to be elucidated.

PMID- 20127493
TI  - New parameters to represent the position of the aorta relative to the spine for
      pedicle screw placement.
AB  - Parameters of the position of the aorta in previous reports were determined for
      anterior surgery. This study evaluated the relative position of the aorta to the
      spine by new parameters, which could enhance the safety of pedicle screw
      placement. Three parameters were defined in a new Cartesian coordinate system. We
      selected an entry point of a left pedicle screw as the origin. The transverse
      plane was determined to include both the bases of the superior facet and to be
      parallel to the upper endplate of the vertebral body. A line connecting the entry
      points of both sides was defined as the X-axis. The angle formed by the Y-axis
      and a line connecting the origin and the center of the aorta was defined as the
      left pedicle-aorta angle. The length of a line connecting the origin and the
      aorta edge was defined as the left pedicle-aorta distance. Distance from the edge
      of the aorta to the X-axis was defined as the pedicular line-aorta distance.
      These parameters were measured preoperatively in 293 vertebral bodies of 24
      patients with a right thoracic curve. We simulated the placement of the pedicle
      screw with variable length and with some direction error. We defined a warning
      pedicle as that when the aorta enters the expected area of the screw. Sensitivity
      analysis was performed to find the warning pedicle ratio in 12 scenarios. The
      left pedicle-aorta angle averaged 29.7 degrees at the thoracic spine and -16.3
      degrees at the lumbar spine; the left pedicle-aorta distance averaged 23.7 and
      55.2 mm; the pedicular line-aorta distance averaged 18.3 and 51.0 mm,
      respectively. The ratio of warning pedicles was consistently high at T4-5 and T10
      12. When a left pedicle screw perforates an anterior/lateral wall of the
      vertebral body, the aorta may be at risk. These new parameters enable surgeons to
      intuitively understand the position of the aorta in surgical planning or in
      placement of a pedicle screw.

PMID- 20127491
TI  - Transient receptor potential channelopathies.
AB  - In the past years, several hereditary diseases caused by defects in transient
      receptor potential channels (TRP) genes have been described. This review
      summarizes our current knowledge about TRP channelopathies and their possible
      pathomechanisms. Based on available genetic indications, we will also describe
      several putative pathological conditions in which (mal)function of TRP channels
      could be anticipated.

PMID- 20127492
TI  - Molecular characterization of the Sasanda LTR copia retrotransposon family
      uncovers their recent amplification in Triticum aestivum (L.) genome.
AB  - Retrotransposons constitute a major proportion of the Triticeae genomes. Genome
      scale studies have revealed their role in evolution affecting both genome
      structure and function and their potential for the development of novel markers.
      In this study, family members of an LTR copia retrotransposon which mediated the
      duplication of the gene encoding the high molecular weight glutenin subunit Bx7
      in cultivar Glenlea were characterized. This novel element was named
      Sasanda_EU157184-1 (TREP3516). High density filters of the Glenlea hexaploid
      wheat BAC library were screened with a Sasanda long terminal repeat (LTR)
      specific probe and approximately 1,075 positive clones representing an estimated
      copy number of 347 elements per haploid genome were identified. The 242 BAC
      clones with the strongest hybridization signal were selected. To maximize
      isolation of complete elements, this subset of clones was screened with a reverse
      transcriptase (RT) domain probe and DNA was isolated from the 133 clones that
      produced a strong hybridization signal. Left (5') and right (3') LTRs as well as
      the RT domains were PCR amplified and sequencing was carried out on the final
      subset of 121 clones. Evolutionary relationships were inferred from a data set
      consisting of 100 RT, 102 5' LTR and 100 3' LTR sequences representing 233, 451
      and 495 informative sites for comparison, respectively. Neighbour-joining tree
      indicated that the element is at least 1.8 million years old and has evolved into
      a minimum of five sub-families. The insertion times of the 89 complete elements
      were estimated based on the divergence between their LTRs. Corroborating the
      inference from the RT domain, analysis of the LTR domains also indicated bursts
      of amplification from 2.6 million years ago (MYA) to now, except for one member
      dated to 4.6 +/- 0.7 MYA, which corresponds to the interval of divergence of
      Triticum and Aegilops (3 MYA) and divergence of Triticum and Rye (7 MYA). In 44
      elements, the 5' and 3' LTRs were identical indicating recent transposition
      activity. The element can be used to develop retrotransposon-based markers such
      as sequence-specific amplified polymorphism, retrotransposon microsatellite
      amplified polymorphism and inter-retrotransposon amplified polymorphism, all of
      which are well suited for genotyping studies.

PMID- 20127494
TI  - Posterior approach to ventrally located spinal meningiomas.
AB  - For the resection of anteriorly located meningiomas, various approaches have been
      used. Posterior approach is less invasive and demanding; however, it has been
      associated with increased risk of spinal cord injury. We evaluated ten
      consecutive patients that underwent surgery for spinal meningiomas. All patients
      were preoperative assessed by neurological examination, computed tomography and
      magnetic resonance imaging. All tumors were ventrally located and removed via a
      posterior approach. Transcranial motor-evoked potentials (TcMEPs), somatosensory
      evoked potential (SSEP) and free running electromyography (EMG) were monitored
      intraoperative. Postoperative all patients had regular follow-up examinations.
      There were four males and six females. The mean age was 68.2 years (range 39-82
      years). In nine out of ten cases, the tumor was located in the thoracic spine. A
      case of a lumbar meningioma was recorded. The most common presenting symptom was
      motor and sensory deficits and unsteady gait, whereas no patient presented with
      paraplegia. All meningiomas were operated using a microsurgical technique via a
      posterior approach. During the operation, free running EMG monitoring prompted a
      surgical alert in case of irritation, whereas TcMEP and SSEP amplitudes remained
      unchanged. Histopathology revealed the presence of typical (World Health
      Organisation grade I) meningiomas. The mean Ki-67/MIB-1 index was 2.75% (range
      0.5-7). None of our patients sustained a transient or permanent motor deficit.
      After a mean follow-up period of 26 months (range 56-16 months), no tumor
      recurrence and no instability were found. Posterior approach for anteriorly
      located meningiomas is a safe procedure with the use of intraoperative
      monitoring, less invasive and well-tolerated especially in older patients.
      Complete tumor excision can be performed with satisfactory results.

PMID- 20127495
TI  - Higher risk of dural tears and recurrent herniation with lumbar micro-endoscopic
      discectomy.
AB  - Existing studies on micro-endoscopic lumbar discectomy report similar outcomes to
      those of open and microdiscectomy and conflicting results on complications. We
      designed a randomised controlled trial to investigate the hypothesis of different
      outcomes and complications obtainable with the three techniques. 240 patients
      aged 18-65 years affected by posterior lumbar disc herniation and symptoms
      lasting over 6 weeks of conservative management were randomised to micro
      endoscopic (group 1), micro (group 2) or open (group 3) discectomy. Exclusion
      criteria were less than 6 weeks of pain duration, cauda equina compromise,
      foraminal or extra-foraminal herniations, spinal stenosis, malignancy, previous
      spinal surgery, spinal deformity, concurrent infection and rheumatic disease.
      Surgery and follow-up were made at a single Institution. A biomedical researcher
      independently collected and reviewed the data. ODI, back and leg VAS and SF-36
      were the outcome measures used preoperatively, postoperatively and at 6-, 12- and
      24-month follow-up. 212/240 (91%) patients completed the 24-month follow-up
      period. VAS back and leg, ODI and SF36 scores showed clinically and statistically
      significant improvements within groups without significant difference among
      groups throughout follow-up. Dural tears, root injuries and recurrent herniations
      were significantly more common in group 1. Wound infections were similar in group
      2 and 3, but did not affect patients in group 1. Overall costs were significantly
      higher in group 1 and lower in group 3. In conclusion, outcome measures are
      equivalent 2 years following lumbar discectomy with micro-endoscopy, microscopy
      or open technique, but severe complications are more likely and costs higher with
      micro-endoscopy.

PMID- 20127496
TI  - Effect of a single dose of pamidronate administered at the time of surgery in a
      rabbit posterolateral spinal fusion model.
AB  - Spinal fusion is usually performed on patients who receive bisphosphonates (BP);
      however, limited data on their action on spinal fusion are available. Previous
      studies in animal models have shown that chronic administrations of BP reduced
      spinal fusion rates, and only one study has shown that a single dose
      administration of zolendronic acid increased fusion rate. The objective of the
      present study was to evaluate if pamidronate (PA), which was previously
      demonstrated to reduce spinal fusion rate when administered continuously for 8
      weeks, would increase the spinal fusion rate if administered in a single dose at
      the time of surgery in a rabbit model. Thirty-two New Zealand rabbits underwent
      an L5-L6 posterolateral intertransverse fusion with iliac crest autograft.
      Animals were randomized to receive either PA 3 mg/kg in a single dose immediately
      after surgery, or normal saline. Animals were killed 8 weeks after surgery and
      fusion was determined by manual palpation and radiographic analysis. Fusion
      healing was obtained in eight rabbits (50%) in the PA group and in four animals
      (25%) in the control group, p = 0.137. In a rabbit model, a single dose of PA did
      not decrease lumbar spinal arthrodesis consolidation rates, but it obtained a
      nonsignificant higher spinal fusion rate.

PMID- 20127497
TI  - Findings from CT, MRI, and PET/CT of a primary malignant melanoma arising in a
      spinal nerve root.
AB  - Primary spinal malignant melanoma is an extremely rare condition. We here
      describe a case of a 71-year-old Asian female presenting with left upper
      extremity tingling sensation. Computed tomography (CT) showed a homogeneously
      enhanced mass occupying the left neural foramen at the C6-7 level. Magnetic
      resonance imaging revealed enhanced mass in intra- and extradural space
      compressing the spinal cord at this level. It also widened the neural foramen
      mimicking neurofibroma or schwannoma. Partial resection of the mass was
      performed. Pathologic diagnosis of the mass was malignant melanoma. Postoperative
      whole body positron emission tomography/CT scan demonstrated an intense (18)F-FDG
      uptake at the residual mass site without abnormal uptake at other sites in the
      body.

PMID- 20127498
TI  - Targeting the bone microenvironment in multiple myeloma.
AB  - Multiple myeloma (MM) is a plasma cell malignancy characterized by the frequent
      development of osteolytic lesions, osteopenia, pathological fractures, and/or
      severe bone pain. In the past few years several potential factors involved in
      this process have been identified and, with the increased knowledge of the
      signaling pathways involved in the regulation of normal osteoblast and osteoclast
      function, have provided us with a better understanding of the contributions of
      the marrow microenvironment to MM bone disease. These studies have identified
      several potential novel targets for treating MM bone disease in addition to the
      current standard treatment of bisphosphonates. In this article, we discuss
      several potential targets for treating MM bone disease as well as novel therapies
      that are in clinical trials for these patients.

PMID- 20127500
TI  - Deep-brain stimulation of the nucleus accumbens in obsessive compulsive disorder:
      clinical, surgical and electrophysiological considerations in two consecutive
      patients.
AB  - Obsessive compulsive disorder is a highly disabling pathological condition which
      in the most severe and drug-resistant form can severely impair social, cognitive
      and interpersonal functioning. Deep-brain stimulation has been demonstrated to be
      an effective and safe interventional procedure in such refractory forms in
      selected cases. We here report the first Italian experience in the treatment of
      this pathology by means of nucleus accumbens stimulation, pointing out to some
      technical data which could be of help in localization of the target.

PMID- 20127499
TI  - Protective effects of heme oxygenase-1 against MPP(+)-induced cytotoxicity in PC
      12 cells.
AB  - Heme oxygenase-1 (HO-1) catalyses the rate-limiting step of heme degradation to
      biliverdin, which is in turn reduced to bilirubin, CO and free iron. HO-1 can be
      induced by several harmful stimuli including oxidative stress, and it has a
      protective role against the cytotoxicity in different cells. 1-Methyl-4-phenyl
      1,2,3,6-tetrahydropyridinium (MPP(+)) is a neurotoxic substance that induces the
      degeneration of dopaminergic neurons. This study examined whether HO-1 can be
      induced by MPP(+) and whether HO-1 has a protective role against the MPP(+)
      induced cytotoxicity in PC-12 cells. MPP(+) triggered a relatively rapid
      induction of HO-1. The MPP(+)-induced cytotoxicity and reactive oxygen species
      (ROS) production markedly increased by HO-1 inhibitor, zinc protoporphyrin-IX
      (ZnPP-IX). The increase of ROS production by ZnPP-IX was completely abrogated by
      either two products of HO (biliverdin or bilirubin) while the increase of
      cytotoxicity by ZnPP-IX was attenuated partially. These suggest that HO-1
      expression might have some cytoprotective effect against MPP(+)-induced
      cytotoxicity.

PMID- 20127501
TI  - Altitudinal changes in carbon storage of temperate forests on Mt Changbai,
      Northeast China.
AB  - A number of studies have investigated regional and continental scale patterns of
      carbon (C) stocks in forest ecosystems; however, the altitudinal changes in C
      storage in different components (vegetation, detritus, and soil) of forest
      ecosystems remain poorly understood. In this study, we measured C stocks of
      vegetation, detritus, and soil of 22 forest plots along an altitudinal gradient
      of 700-2,000 m to quantify altitudinal changes in carbon storage of major forest
      ecosystems (Pinus koraiensis and broadleaf mixed forest, 700-1,100 m; Picea and
      Abies forest, 1,100-1,800 m; and Betula ermanii forest, 1,800-2,000 m) on Mt
      Changbai, Northeast China. Total ecosystem C density (carbon stock per hectare)
      averaged 237 t C ha(-1) (ranging from 112 to 338 t C ha(-1)) across all the
      forest stands, of which 153 t C ha(-1) (52-245 t C ha(-1)) was stored in
      vegetation biomass, 14 t C ha(-1) (2.2-48 t C ha(-1)) in forest detritus
      (including standing dead trees, fallen trees, and floor material), and 70 t C ha(
      1) (35-113 t C ha(-1)) in soil organic matter (1-m depth). Among all the forest
      types, the lowest vegetation and total C density but the highest soil organic
      carbon (SOC) density occurred in Betula ermanii forest, whereas the highest
      detritus C density was observed in Picea and Abies forest. The C density of the
      three ecosystem components showed distinct altitudinal patterns: with increasing
      altitude, vegetation C density decreased significantly, detritus C density first
      increased and then decreased, and SOC density exhibited increasing but
      insignificant trends. The allocation of total ecosystem C to each component
      exhibited similar but more significant trends along the altitudinal gradient. Our
      results suggest that carbon storage and partitioning among different components
      in temperate forests on Mt Changbai vary greatly with forest type and altitude.

PMID- 20127502
TI  - Cholesterol biotransformation to androsta-1,4-diene-3,17-dione by growing cells
      of Chryseobacterium gleum.
AB  - Cholesterol oxidase activity was studied during biotransformation of cholesterol
      to androsta-1,4-diene-3,17-dione (ADD) by Chryseobacterium gleum. Spent LB media,
      containing cholesterol (3 mM approximately = 1 g l(-1)) where the bacterium was
      grown for 24 h, at 30 degrees C with constant shaking at 120 rpm, had the highest
      enzyme activity (167 U mg(-1)). The growing cells produced 0.076 g ADD from 1 g
      cholesterol l(-1).

PMID- 20127503
TI  - hAT transposable elements and their derivatives: an analysis in the 12 Drosophila
      genomes.
AB  - Transposable elements (TEs) comprise a significant fraction of the genome, and
      some models of the TE "life cycle" suggest that, in the last phases of the cycle,
      TEs should be represented, in the genomes, by inactive and degenerated copies. In
      this study, we analyzed, using a bioinformatics approach, the autonomous hAT
      elements and their derivatives (active non-autonomous, MITE relatives and
      degenerated copies) in 12 Drosophila genomes. We found 28 hAT elements that had
      derivatives. Most copies had features that suggested that they were active, while
      only a few degenerated copies were found. Because hAT elements comprise an
      evolutionarily old superfamily, one should expect to find many degenerated copies
      within the genome, although this was not observed in our study. These results
      suggest that primarily active copies of hAT elements are maintained in the
      euchromatic regions of the genome and that degenerated copies are removed from
      the genome by natural selection.

PMID- 20127504
TI  - Is incarceration a contributor to health disparities? Access to care of formerly
      incarcerated adults.
AB  - Despite the disproportionate prevalence of incarceration in communities of color,
      few studies have examined its contribution to health disparities. We examined
      whether a lifetime history of incarceration is associated with recent access to
      medical and dental care. We performed a secondary data analysis of the 2007 Los
      Angeles County Health Survey, a population-based random-digit-dialing telephone
      survey of county households. Any history of incarceration in a
      prison/jail/detention center as an adult was assessed for a random subsample.
      Bivariate and multivariate logistic regression analyses examined whether
      incarceration history was associated with access to care, controlling for other
      characteristics. Ten percent of our study population reported a history of
      incarceration. While persons with an incarceration history were similar to their
      peers with regard to health and insurance status, their access to medical and
      dental care was worse. Incarceration history was independently associated with
      disparities in access to care. Interventions to improve the health of communities
      affected by high rates of incarceration could include efforts that enable access
      to care for formerly incarcerated adults.

PMID- 20127505
TI  - Beyond affordability: the impact of nonfinancial barriers on access for uninsured
      adults in three diverse communities.
AB  - Most proposals to improve access for uninsured adults focus on removing financial
      barriers to health care. Health services researchers have long recognized,
      however, that access to care is a multidimensional concept consisting of both
      financial and nonfinancial dimensions. While financial barriers faced by those
      without health insurance have been well-documented, it is not known to what
      degree nonfinancial barriers limit access for those without coverage. In this
      study we sought to identify the types and frequencies of nonfinancial access
      barriers faced by low-income uninsured adults, as well as determine how
      frequently nonfinancial barriers coexist with financial access barriers in this
      population. We conducted a telephone survey of 1,118 low-income uninsured adults
      in Alameda, California, Austin, Texas, and Southern Maine who had enrolled in
      local access programs funded through the Robert Wood Johnson Foundation's
      Communities in Charge initiative. Financial barriers were the most often cited
      barrier to access in each of the three groups, though nonfinancial barriers were
      often cited as well. Across all three populations, one-third to one-half of
      respondents with financial access barriers also cited one or more nonfinancial
      barriers as contributing to their problems accessing health care. Our results
      suggest that many uninsured adults face nonfinancial health care barriers in
      addition to their well-documented financial challenges. Health reform efforts
      must address both types of barriers in order to maximally improve access for the
      uninsured population.

PMID- 20127507
TI  - Pornography, normalization, and empowerment.
AB  - Opponents and proponents of erotic representations (referred to hereafter as
      "pornography") have described the effects of pornography from their perspective.
      Little, however, has been done in the way of research to investigate these claims
      from the consumer's point of view. This especially has been so regarding the
      positive impact of such consumption on a person's sex life. Using a study group
      of 245 college students, we examined this question in a framework of scripting
      theory. We wanted to see whether viewing pornography appeared to expand sexual
      horizons through normalization and facilitate a willingness to explore new sexual
      behaviors and sexual relationships through empowerment. The data supported this
      viewpoint and further showed the effects to be mediated by gender and sexual
      preference identity. They suggested, however, that established scripts were
      extended rather than abandoned. We conclude with connections between our findings
      and the widespread viewing of pornography in contemporary society.

PMID- 20127506
TI  - Neighborhood impact on healthy food availability and pricing in food stores.
AB  - Availability and price of healthy foods in food stores has the potential to
      influence purchasing patterns, dietary intake, and weight status of individuals.
      This study examined whether demographic factors of the store neighborhood or
      store size have an impact on the availability and price of healthy foods in
      sample of grocery stores and supermarkets. The Nutrition Environment Measures
      Study-Store (NEMS-S) instrument, a standardized observational survey, was
      utilized to evaluate food stores (N = 42) in a multi-site (Vermont and Arkansas)
      study in 2008. Census data associated with store census tract (median household
      income and proportion African-American) were used to characterize store
      neighborhood and number of cash registers was used to quantify store size. Median
      household income was significantly associated with the NEMS healthy food
      availability score (r = 0.36, P < 0.05); neither racial composition (r = -0.23, P
      = 0.14) nor store size (r = 0.27, P = 0.09) were significantly related to the
      Availability score. Larger store size (r = 0.40, P < 0.01) was significantly
      associated with the NEMS-S Price scores, indicating more favorable prices for
      healthier items; neither racial composition nor median household income were
      significantly related to the Price score (P's > 0.05). Even among supermarkets,
      healthier foods are less available in certain neighborhoods, although, when
      available, the quality of healthier options did not differ, suggesting that
      targeting availability may offer promise for policy initiatives. Furthermore,
      increasing access to larger stores that can offer lower prices for healthier
      foods may provide another avenue for enhancing food environments to lower disease
      risk.

PMID- 20127508
TI  - Developmental trajectories of girls' and boys' delinquency and associated
      problems.
AB  - Developmental trajectories in delinquency through adolescence were studied along
      with family and peer relationship problems. Drawing from eight waves of data over
      seven years, we conducted trajectory analyses with a sample of 746 students (402
      girls; 344 boys). Analyzing girls and boys together, a five-class model emerged:
      60% of the adolescents rarely reported delinquency; 27.7% reported low initial
      levels with moderate levels of delinquency over time; 6% in the late onset group
      reported initially low and rising levels of delinquency; 5% in the early onset
      group reported moderate initial levels which increased and then decreased in
      later adolescence. A small group of only boys (1.3%) labeled chronic reported
      high initial levels of delinquency that increased over time. Group comparisons
      revealed problems in internalizing, parent and peer relationship problems. The
      findings provide direction for early identification and interventions to curtail
      the development of delinquency.

PMID- 20127509
TI  - The impact of statistical adjustment on conditional standard errors of
      measurement in the assessment of physician communication skills.
AB  - The use of standardized patients to assess communication skills is now an
      essential part of assessing a physician's readiness for practice. To improve the
      reliability of communication scores, it has become increasingly common in recent
      years to use statistical models to adjust ratings provided by standardized
      patients. This study employed ordinary least squares regression to adjust
      ratings, and then used generalizability theory to evaluate the impact of these
      adjustments on score reliability and the overall standard error of measurement.
      In addition, conditional standard errors of measurement were computed for both
      observed and adjusted scores to determine whether the improvements in measurement
      precision were uniform across the score distribution. Results indicated that
      measurement was generally less precise for communication ratings toward the lower
      end of the score distribution; and the improvement in measurement precision
      afforded by statistical modeling varied slightly across the score distribution
      such that the most improvement occurred in the upper-middle range of the score
      scale. Possible reasons for these patterns in measurement precision are
      discussed, as are the limitations of the statistical models used for adjusting
      performance ratings.

PMID- 20127510
TI  - BNYVV-derived dsRNA confers resistance to rhizomania disease of sugar beet as
      evidenced by a novel transgenic hairy root approach.
AB  - Agrobacterium rhizogenes-transformed sugar beet hairy roots, expressing dsRNA
      from the Beet necrotic yellow vein virus replicase gene, were used as a novel
      approach to assess the efficacy of three intron-hairpin constructs at conferring
      resistance to rhizomania disease. Genetically engineered roots were similar in
      morphology to wild type roots but were characterized by a profound abundancy,
      rapid growth rate and, in some cases, plagiotropic development. Upon challenge
      inoculation, seedlings showed a considerable delay in symptom development
      compared to untransformed or vector-transformed seedlings, expressing dsRNA from
      an unrelated source. The transgenic root system of almost all seedlings contained
      no or very low virus titer while the non-transformed aerial parts of the same
      plants were found infected, leading to the conclusion that the hairy roots
      studied were effectively protected against the virus. This readily applicable
      novel method forms a plausible approach to preliminarily evaluate transgenic
      rhizomania resistance before proceeding in transformation and whole plant
      regeneration of sugar beet, a tedious and time consuming process for such a
      recalcitrant crop species.

PMID- 20127512
TI  - BMES 2009 Distinguished Achievement Lecture Award: BMES Annual Meeting October 9,
      2009.

PMID- 20127511
TI  - Origin of the electrocardiographic U wave: effects of M cells and dynamic gap
      junction coupling.
AB  - The electrophysiological basis underlying the genesis of the U wave remains
      uncertain. Previous U wave modeling studies have generally been restricted to 1-D
      or 2-D geometries, and it is not clear whether the U waves generated by these
      models would match clinically observed U wave body surface potential
      distributions (BSPDs). We investigated the role of M cells and transmural
      dispersion of repolarization (TDR) in a 2-D, fully ionic heart tissue slice model
      and a realistic 3-D heart/torso model. In the 2-D model, while a U wave was
      present in the ECG with dynamic gap junction conductivity, the ECG with static
      gap junctions did not exhibit a U wave. In the 3-D model, TDR was necessary to
      account for the clinically observed potential minimum in the right shoulder area
      during the U wave peak. Peak T wave simulations were also run. Consistent with at
      least some clinical findings, the U wave body surface maximum was shifted to the
      right compared to the T wave maximum. We conclude that TDR can account for the
      clinically observed U wave BSPD, and that dynamic gap junction conductivity can
      result in realistic U waves generated by M cells.

PMID- 20127513
TI  - Interorganizational network changes among health organizations in the Brazos
      Valley, Texas.
AB  - Community health development is a process by which a community identifies factors
      influencing population health, assesses available resources to build the capacity
      to plan and take action, and implement interventions to address identified needs.
      At its core, community health development targets structural change and
      infrastructure development to facilitate more efficient and effective health
      service delivery systems and environmental changes to support improvements in
      community health. One indicator of structural change and common measure of
      community capacity is the relationships among the network of organizations that
      comprise that system. The Brazos Valley has employed a community health
      development approach to population health improvement in partnership with the
      Center for Community Health Development. Changes in interorganizational networks
      illustrate progress in the Brazos Valley. Contextual factors provide some insight
      into how the process has unfolded.

PMID- 20127514
TI  - Expression of UreB and HspA of Helicobacter pylori in silkworm pupae and
      identification of its immunogenicity.
AB  - For mass production of urease B subunit (UreB) and heat shock protein A subunit
      (HspA) of Helicobacter pylori with Bombyx mori nuclear polyhedrosis virus (BmNPV)
      baculovirus expression system (BES) and to determine whether they could be used
      as an oral vaccine against H. pylori, besides, to determine the time course of
      expressed recombinant protein and the optimum acquisition time directly through
      green fluorescence, HspA and enhanced green fluorescence protein (EGFP) genes
      were cloned into vector pFastBacDual to form donor vector pFastBacDual-(EGFP)
      (HspA), UreB gene was cloned into vector pFastBacDual to form donor vector
      pFastBacDual-UreB,then they were transformed into E. coli BmDH10Bac to obtain the
      recombinant Bacmid-(EGFP) (HspA) and Bacmid-UreB respectively. They were used to
      transfect BmN cells and generated the recombinant baculovirus BmNPV-(EGFP) (HspA)
      and BmNPV-UreB. Using these recombinant baculovirus BmNPV-(EGFP) (HspA) and BmNPV
      UreB inoculated the silkworm pupae, a recombinant HspA and UreB protein were
      expressed in silkworm pupae, which were around 13 and 62 kDa in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot analysis.
      After oral immunization of mice, serum specific IgG antibodies against HspA and
      UreB in vaccine group were much higher than that in mock and native silkworm
      powder control groups. The results indicated that the expressed recombinant HspA
      and UreB in silkworm pupae would possess good immunogenicity. In addition, when
      EGFP and HspA proteins were expressed, a direct correlation between the increase
      in intensity of fluorescence and HspA concentration.

PMID- 20127515
TI  - Isolation and characterization of three duplicated PISTILLATA genes in Brassica
      napus.
AB  - Three coding region cDNAs of duplicated PISTILLATA-like (PI-like) MADS-box genes,
      BnPI-1, BnPI-2 and BnPI-3, were isolated from B. napus by RT-PCR. The sequence
      analysis showed that the three PI cDNAs possessed 627, 627 and 625 nucleotides,
      respectively, and their nucleotide sequences had 96.49-98.72% similarity. Due to
      a deletion of two nucleotides, the protein sequence in the downstream of the
      frameshift site was altered in BnPI-3. Therefore, there were only 171 amino acids
      coded by BnPI-3, while there were 208 ones coded by BnPI-1 or BnPI-2. The deduced
      amino acid identity between BnPI-1 and BnPI-2 was 97.6% and the amino acid
      sequence of BnPI-1 and BnPI-2 shared 72.6% identity with BnPI-3. The deduced
      amino acid sequences of the coded proteins indicated high homology with the
      members of the PI family of MADS-box proteins. RT-PCR analysis showed that BnPI
      transcription was only detectable in petals and stamens. The yeast two-hybrid
      assays results showed that the three BnPI proteins exhibited different
      dimerization affinities with three BnAP3. BnPI-1 and BnPI-2 could form strong
      heterodimers with BnAP3. The dimerization affinity of BnPI-1 with BnAP3-4 is the
      strongest in all the combinations, while the affinity of BnPI-3 with BnAP3-4 is
      the weakest. The dimerization affinity to BnAP3-4 of BnPI-1 is 3.5 times of that
      of BnPI-3. The distinguished weak interaction to AP3 of BnPI-3 is probably due to
      the loss of the PI motif. The divergences of sequence and affinity of protein
      interaction might reflect some functional divergence of the three PI genes in B.
      napus.

PMID- 20127516
TI  - Construction of NF-kappaB-targeting RNAi adenovirus vector and the effect of NF
      kappaB pathway on proliferation and apoptosis of vascular endothelial cells.
AB  - To construct a recombinant adenovirus vector expressing a RNAi for the Nuclear
      Factor kappa B (NF-kappaB)/p65 gene and use it to explore the role of the NF
      kappaB pathway on the regulation of proliferation and apoptosis of vascular
      endothelial cells. A recombinant adenovirus containing a RNAi cassette targeting
      the p65 gene was constructed, and its silencing effect on p65 was detected by
      Western blot analysis in ECV304 cells. Expression of the p65 protein in ECV304
      cells was efficiently down-regulated by the RNAi adenovirus for more than 6 days.
      ECV304 cells proliferation and apoptosis were measured using the MTT assay and
      flow cytometry, respectively. Blocking the NF-kappaB pathway with the RNAi
      adenovirus substantially decreased the proliferation of ECV304 cells, but only
      slightly affected cell apoptosis. We used a NF-kappaB/p65-targeting RNAi
      adenovirus to demonstrate the role of the NF-kappaB pathway in the regulation of
      ECV304 cell proliferation. This adenovirus may serve as an important tool to
      study the NF-kappaB pathway.

PMID- 20127517
TI  - Abnormal expression of NRF-2alpha in hepatocellular carcinoma identified with a
      newly prepared monoclonal antibody against human NRF-2alpha protein.
AB  - Human nuclear respiratory factor 2 alpha subunit (NRF-2alpha) is fundamentally
      important to cell function and the development. We aimed to establish the
      monoclonal antibody (MAb) against the human NRF-2alpha protein and to investigate
      its distribution in human hepatocellular carcinoma (HCC) and tumor-adjacent
      tissues. The 6* His-NRF-2alpha fusion protein was successfully induced and
      purified. One monoclonal antibody (MAb) against human NRF-2alpha, 1-D10-E1-B11-G3
      (IgG1), effective in detecting the recombinant and the cellular protein, was
      characterized. Using immunohistochemical analysis, the expression of NRF-2alpha
      was investigated in 38 cases of HCC specimens and 14 cases of tumor-adjacent
      specimens. Staining was found positive in 9 cases of HCC tissues (23.7%) and 8
      cases of normal hepatic tissues (57.1%). The higher-grade frequency of expression
      of NRF-2alpha in tumor-adjacent tissues was significantly higher (P < 0.01) than
      that in tumor tissues, suggesting that NRF-2alpha may play important roles in
      carcinogenesis of HCC.

PMID- 20127518
TI  - The cardioprotective effect of fluvastatin on ischemic injury via down-regulation
      of toll-like receptor 4.
AB  - To determine whether the cardioprotection effect of fluvastatin mediates by toll
      like receptor 4 (TLR4) signaling pathway, fifty Sprague-Dawley rats were randomly
      divided into five groups: sham operation group, ischemia/reperfusion (I/R) group,
      fluvastatin groups (high-dosage, medium-dosage, low-dosage, n = 10 in each
      group). Except sham operation group, the rest four groups of rats were
      artificially afflicted with coronary occlusion for 30 min, then reperfusion 2 h.
      Light microscope and transmission electronic microscope were used to observe
      structural changes of myocardium. RT-PCR was used to measure TLR4 mRNA expression
      level, TLR4 protein expression was detected by immunohistochemistry. Western blot
      was used to measure myocardial NF-kappaB protein level; ELISA was used to measure
      the level of TNF-alpha in myocardium. The results demonstrated that fluvastatin
      treatment markedly decreased ischemic injury caused by ischemia/reperfusion, and
      inhibited the expression levels of TLR4, TNF-alpha and NF-kappaB, all of which up
      regulated by ischemia/reperfusion. Taken together, our results suggest that
      proper dosage of fluvastatin may have protective effect on the ischemic injury
      mediated by ischemia/reperfusion in the hearts, which might be associated with
      inhibition of TLR4 signaling pathway and inflammatory response during
      ischemia/reperfusion.

PMID- 20127519
TI  - Role of metallothionein in differentiation of leukemia cells.
AB  - Metallothioneins (MTs), a group of small, cystein-rich proteins, possess various
      functions, including metal detoxification and homeostasis. We here report new
      findings on the participation of MT in cellular differentiation processes. MT
      isogene transcription was significantly increased in phorbol-12-myristate-13
      acetate (PMA) incubated leukemic DAMI cells, which supports its role in cellular
      differentiation. To further address this possibility, we constructed one stable
      MT-2A overexpressing DAMI cell line. Increase of cell size, intracellular
      granulation and megakaryocytic specific antigen expression such as CD41 and CD42,
      and arresting cell proliferation have validated the role of MT in differentiation
      in this cell line.

PMID- 20127520
TI  - Complement factor H Y402H gene polymorphism and coronary heart disease
      susceptibility: a meta-analysis.
AB  - The complement factor H (CFH) Y402H (T1277C) gene polymorphism has been reported
      to be associated with coronary heart disease (CHD), but results were conflicting.
      To evaluate the role of the variant in CHD, we performed meta-analyses of all
      available data. Both electronic and manual searches were performed, all relevant
      studies were identified. ORs with 95% confidential intervals (CI) under
      codominant (CC versus TT, TC versus TT), dominant (CC + TC versus TT) and
      recessive (CC versus TT + TC) models were calculated. Publication bias was
      addressed. Ten studies including 11 cohorts comprising of 29,764 participants
      were included. No association between the CFH T1227C polymorphism and CHD could
      be found. (For overall analysis: dominant model, OR = 1.04, 95%CI: 0.97-1.11;
      recessive model, OR = 1.04, 95%CI: 0.97-1.11; for Caucasian subgroup: OR = 1.08
      95%CI: 0.92-1.27; recessive model, OR = 1.03, 95%CI: 0.96-1.11). Two studies
      reported positive results in separate population (Caucasian study: recessive
      model, OR = 0.51, 95%CI: 0.30-0.86; Asians study: dominant model, OR = 2.37,
      95%CI: 1.13-4.96). Current evidence do not support the association between the
      CFH T1277C polymorphism and CHD risk among common population. The association,
      which could be influenced by CHD onset age, CHD risk factors status and genetics
      backgrounds, might be significant in some population. More studies on different
      CHD onset ages and risk factor status should be encouraged.

PMID- 20127521
TI  - Engineering of Bacillus lipase by directed evolution for enhanced thermal
      stability: effect of isoleucine to threonine mutation at protein surface.
AB  - A lip gene from a Bacillus isolate was cloned and expressed in E. coli. By
      thermal denaturation analysis, T(1/2) of lipase was observed to be 7 min at 50
      degrees C with less than 10% activity after 1 h incubation at 50 degrees C. To
      expand the functionality of cloned lipase, attempts have been made to create
      thermostable variants of lip gene. A lipase variant with an isoleucine to
      threonine amino acid substitution at the protein surface was isolated that
      demonstrated higher thermostability than its wild type predecessor. To explore
      the structure-function relationship, the lip gene product of wild type (WT) and
      mutant was characterized in detail. The mutation enhanced the specific activity
      of enzyme by 2-folds when compared with WT. The mutant enzyme showed enhanced
      T(1/2) of 21 min at 50 degrees C. The kinetic parameters of the mutant enzyme
      were significantly altered. The mutant enzyme displayed higher affinity for
      substrate (decreased K ( m )) in comparison to the wild type. The k (cat) and
      catalytic efficiency (k (cat)/K ( m )) of mutant were also enhanced by two and
      five times, respectively, as compared with the WT. The mutation resides on the
      part of helix which is exposed to the solvent and away from the catalytic triad.
      The replacement of a solvent exposed hydrophobic residue (Ile) in WT with a
      hydrophilic residue (Thr) in mutant might impart thermostability to the protein
      structure.

PMID- 20127522
TI  - Molecular characterization and expression patterns of serine/arginine-rich
      specific kinase 3 (SPRK3) in porcine skeletal muscle.
AB  - SRPK3 is a protein kinase belonging to serine/arginine protein kinases (SRPK)
      family, which phosphorylates serine/arginine repeat-containing proteins, and is
      controlled by a muscle-specific enhancer directly regulated by MEF2. In this
      study, a full-length cDNA of the porcine SRPK3 gene encoding a 566 amino acid
      protein was isolated. It contains 14 exons over approximately 4.3 kb. The deduced
      amino acid sequence of porcine SRPK3 contains a bipartite kinase domain, and
      shows high similarities to their corresponding human and cattle homologues.
      Tissue distribution analysis indicated that porcine SRPK3 mRNAs are highly
      expressed in heart and skeletal muscle especially in uterus and parorchis, but at
      low level in brain, stomach, small intestine, and ovary. Expression pattern of
      SRPK3 was similar in Large White and Chinese Meishan breeds. Both the two breeds
      had the highest expression levels at fetal 65 days (P < 0.01), and decreased
      while the age increased until 60 days old, then increased at 120 days (P < 0.01)
      and decreased at 180 days (P < 0.05). However, at fetal 65 days, the mRNA
      abundance of SRPK3 in Large White was 12.5-fold higher than in Meishan pigs (P <
      0.01), whereas at 180 days, the abundance in Meishan was 3.4-fold higher than in
      Large White pigs (P < 0.01). These results suggest that the SRPK3 gene might be
      an important gene of skeletal muscle development and also provides basic
      molecular information useful for further studies on its roles in porcine skeletal
      muscle.

PMID- 20127523
TI  - Atrial activity estimation from atrial fibrillation ECGs by blind source
      extraction based on a conditional maximum likelihood approach.
AB  - This work presents a spatial filtering method for the estimation of atrial
      fibrillation activity in the cutaneous electrocardiogram. A linear extraction
      filter is obtained by maximising the extractor output power on the significant
      spectral support of the signal of interest. An iterative procedure based on a
      quasi-maximum likelihood estimator is proposed to jointly estimate the
      significant spectral support and the extraction filter. Compared with a
      previously proposed spatio-temporal blind source separation method, our approach
      yields an improved atrial activity signal estimate as quantified by a higher
      spectral concentration of the extractor output. The proposed methodology can
      readily be adapted to signal extraction problems in other application domains.

PMID- 20127524
TI  - Anti-apoptotic actions of PPAR-gamma against ischemic stroke.
AB  - Stroke is a leading cause of adult disability and mortality. Diabetes is a major
      risk factor for stroke. Patients with diabetes have a higher incidence of stroke
      and a poorer prognosis after stroke. Peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) is a ligand-modulated transcriptional factor and a therapeutic
      target for treating type II diabetes. It is well-documented that activation of
      PPAR-gamma can also attenuate postischemic inflammation and damage. In this
      review, we focus on the newly revealed anti-apoptotic actions of PPAR-gamma
      against cerebral ischemia. PPAR-gamma, by increasing superoxide
      dismutase/catalase and decreasing nicotinamide adenine dinucleotide phosphate
      oxidase levels, attenuated ischemia-induced reactive oxygen species and
      subsequently alleviated the postischemic degradation of Bcl-2, Bcl-xl, and Akt.
      The preserved Akt phosphorylated Bad. Meanwhile, PPAR-gamma also promotes the
      transcription of 14-3-3epsilon. Elevated 14-3-3epsilon binds and sequesters p-Bad
      and prevents Bad translocation to neutralize the anti-apoptotic function of Bcl
      2. This review further supports the notion that PPAR-gamma may serve as a
      potential therapeutic target for treating ischemic stroke.

PMID- 20127526
TI  - Incidence of koilonychia and atrophy of the lingual papillae in a patient with
      iron-deficiency anemia.

PMID- 20127525
TI  - Phospholipase A2 and its molecular mechanism after spinal cord injury.
AB  - Phospholipases A(2) (PLA(2)s) are a diverse family of lipolytic enzymes which
      hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce
      free fatty acids and lysophospholipids. These products are precursors of
      bioactive eicosanoids and platelet-activating factor which have been implicated
      in pathological states of numerous acute and chronic neurological disorders. To
      date, more than 27 isoforms of PLA(2) have been found in the mammalian system
      which can be classified into four major categories: secretory PLA(2), cytosolic
      PLA(2), Ca(2+)-independent PLA(2), and platelet-activating factor
      acetylhydrolases. Multiple isoforms of PLA(2) are found in the mammalian spinal
      cord. Under physiological conditions, PLA(2)s are involved in diverse cellular
      responses, including phospholipid digestion and metabolism, host defense, and
      signal transduction. However, under pathological situations, increased PLA(2)
      activity, excessive production of free fatty acids and their metabolites may lead
      to the loss of membrane integrity, inflammation, oxidative stress, and subsequent
      neuronal injury. There is emerging evidence that PLA(2) plays a key role in the
      secondary injury process after traumatic spinal cord injury. This review outlines
      the current knowledge of the PLA(2) in the spinal cord with an emphasis being
      placed on the possible roles of PLA(2) in mediating the secondary SCI.

PMID- 20127527
TI  - Effect of iron chelator deferasirox on chronic anemia and thrombocytopenia in a
      transfusion-dependent patient with myelodysplastic syndrome.

PMID- 20127528
TI  - Natural pregnancy and delivery after unrelated bone marrow transplantation using
      fludarabine-based regimen in a Fanconi anemia patient.

PMID- 20127529
TI  - Formulation and evaluation of a protein-loaded solid dispersions by non
      destructive methods.
AB  - The purpose of this investigation was to develop solid dispersion (SD)
      formulation of cyclosporine (CyA) using polyethylene glycol (PEG-6000) to enhance
      its dissolution rate followed by nondestructive method for the prediction of both
      drug and carrier. SD formulations were prepared by varying the ratio of CyA and
      PEG-6000 by solvent evaporation technique and characterized by dissolution,
      scanning electron microscopy (SEM), differential scanning calorimetry (DSC),
      Fourier transform infrared (FTIR), powder X-ray diffraction (PXRD), near infrared
      (NIR) and near infrared chemical imaging (NIR-CI). Dissolution data revealed
      enhanced dissolution of CyA when compared with pure CyA. DSC results showed that
      the crystallinity of PEG-6000 has decreased as indicated by decrease in the
      enthalpy of fusion and melting peak in the formulations. FTIR data demonstrated
      no chemical interaction between drug and carrier. The surface morphology of SD
      formulations was similar to PEG-6000 particle. NIR-CI disclosed homogeneity of SD
      matrix as indicated by symmetrical histograms with smaller values of skewness.
      Similar to NIR, a multivariate peak evaluation with principal component analysis
      and partial least square (PLS) were carried out with PXRD spectral data. PLS
      models with both techniques showed good correlation coefficient and smaller value
      of root mean square of errors. The accuracy of model for predicting CyA and PEG
      6000 in NIR and PXRD data were 5.22%, 5.35%, 5.27%, and 2.10%, respectively. In
      summary, chemometric applications of non-destructive method sensors provided a
      valuable means of characterization and estimation of drug and carrier in the
      novel formulations.

PMID- 20127530
TI  - Anesthetic dose neuraxial blockade increases the success rate of external fetal
      version: a meta-analysis.
AB  - PURPOSE: This study is a meta-analysis evaluating the efficacy of central
      neuraxial blockade (CNB) (epidural or spinal) to facilitate fetal version.
      METHODS: A search with no language restriction for all available randomized
      controlled trials (RCT) was conducted in PUBMED on July 2, 2009, EMBASE 1980 to
      2009 Week 27, Ovid MEDLINE(R) 1950 to Week 4 in June 2009, EBM Reviews - Cochrane
      Central Register of Controlled Trials 2(nd) Quarter 2009, and CINAHL on July 4,
      2009. Reference lists of all studies were also checked. Two investigators
      extracted data independently. The optimal information size (OIS) was calculated
      on a 50% failure rate of fetal version for a relative reduction of 25% (alpha =
      0.05 two-tailed, beta = 0.2). RESULTS: The OIS was 494. Seven RCTs were found,
      including 681 pregnant women with a Jadad score from 1 to 3. Central neuraxial
      blockade increases the success rate of fetal version (risk ratio [RR] = 1.44; 95%
      confidence interval [CI] = 1.16-1.79; P = 0.001) (random effects model; I(2) =
      30.25%; P value for heterogeneity = 0.20). Three studies used a CNB at anesthetic
      dose of local anesthetic (RR = 1.95; 95% CI = 1.46-2.60; P < 0.001; I(2) = 0.00%;
      P value for heterogeneity = 0.86; number needed to treat = 4; 95% CI = 3-6). Four
      studies used an analgesic dose (RR = 1.18; 95% CI = 0.94-1.49; P = 0.15; I(2) =
      0.00%; P value for heterogeneity = 0.77). These two subgroups were significantly
      different one from the other with a P value of 0.007. CONCLUSION: Anesthetic dose
      neuraxial blockade increases the success rate of external fetal version.

PMID- 20127531
TI  - The relationship between glycosylated hemoglobin and perioperative glucose
      control in patients with diabetes.
AB  - PURPOSE: Hyperglycemia and elevated glycosylated hemoglobin (HbA(1c)) are
      associated with perioperative morbidity in patients with diabetes, but the
      relationship between long-term glycemic control and perioperative glucose control
      is unknown. The purpose of this study was to determine the relationship between
      glycosylated hemoglobin (HbA(1c)) and perioperative glucose in fasting patients
      with type 2 diabetes undergoing elective non-cardiac surgery. METHODS: This was a
      prospective observational study of 244 adult patients with type 2 diabetes who
      were evaluated before elective non-cardiac surgery at a preoperative medicine
      clinic in a tertiary care medical centre during the period September 2004 to May
      2005. Preoperative HbA(1c) levels were determined, and preoperative and
      postoperative glucose values were measured on the day of surgery. The primary
      outcome variables were preoperative and postoperative blood glucose values.
      RESULTS: Half of all study patients had an HbA(1c) > or = 7%, including 23% of
      patients with HbA(1c) >/= 8%. HbA(1c) levels predict preoperative glucose levels,
      and preoperative glucose levels and duration of surgery predict postoperative
      glucose levels. Glucose levels in one-third of the patients with type 2 diabetes
      decreased during surgery without administration of insulin or glucose-regulating
      medications. CONCLUSION: HbA(1c) values may serve as biomarkers for glucose
      control during the immediate perioperative period in patients with type 2
      diabetes undergoing elective surgery.

PMID- 20127532
TI  - Neurolytic blocks: when, how, why.
AB  - Interventional techniques are divided into two categories: neuroablative and
      neuromodulatory procedures. Neuroablation is the physical interruption of pain
      pathways either surgically, chemically or thermally. Neuromodulation is the
      dynamic and functional inhibition of pain pathways either by administration of
      opioids and other drugs intraspinally or intraventricularly or by stimulation.
      Neuroablative techniques for cancer pain treatment have been used for more than a
      century. With the development of imaging facilities such as fluoroscopy,
      neuroablative techniques can be performed more precisely and efficiently.

PMID- 20127533
TI  - Effects of intraperitoneal levobupivacaine on pain after laparoscopic
      cholecystectomy: a prospective, randomized, double-blinded study.
AB  - OBJECTIVES: We aimed to determine the effects of intraperitoneal administration
      of levobupivacaine on pain after laparoscopic cholecystectomy in a prospective,
      randomized, double-blinded, placebo-controlled trial. METHODS: In all patients,
      infiltration of levobupivacaine 0.25% (15 mL) was used prior to skin incisions
      for trocar insertion. After pneumoperitoneum was achieved, patients were
      allocated randomly to receive intraperitoneally either 40 mL of 0.25%
      levobupivacaine (LB group, n=20) or normal saline (NS group, n=20) under direct
      vision into the hepatodiaphragmatic lodge and above the gallbladder. Data of
      intraoperative variables, postoperative pain relief, rescue analgesic
      consumption, side effects, and patient satisfaction were followed in both groups.
      RESULTS: The postoperative pain scores were significantly lower in the first half
      hour period in the LB group than in the NS group (p<0.05). However, the incidence
      of right shoulder pain was not significantly different between the LB group (10%)
      and NS group (15%). The mean dose of meperidine consumption and the number of
      patients needing rescue meperidine were significantly lower in the LB group than
      in the NS group (p<0.05). Significantly lower vomiting incidence and increased
      patient satisfaction were determined in the LB group compared to the NS group
      (p<0.05). CONCLUSION: Intraperitoneal administration of 40 mL levobupivacaine
      0.25% given immediately after pneumoperitoneum into the hepatodiaphragmatic lodge
      and above the gallbladder demonstrated useful effects on postoperative pain
      relief after laparoscopic cholecystectomy, especially in the early postoperative
      period, and reduced postoperative rescue analgesic requirement, with excellent
      patient satisfaction. There were no LB-related complications or side effects.

PMID- 20127534
TI  - The relationship between electrodiagnostic severity and Washington Neuropathic
      Pain Scale in patients with carpal tunnel syndrome.
AB  - OBJECTIVES: We undertook this study to examine the relationships between clinical
      symptoms as evaluated by Washington Neuropathic Pain Scale (NPS) and
      electrodiagnostic classification in patients with carpal tunnel syndrome (CTS).
      METHODS: Eighty patients with unilateral CTS were included in this study. After
      diagnosis of CTS by electromyography, all patients completed a 10-item
      questionnaire (NPS). RESULTS: A statistically significant correlation between
      total NPS score and severity of CTS was found (p=0.013, r=0.276). CONCLUSION: The
      present study indicates that using NPS might be useful in evaluating the clinical
      outcome of patients with CTS.

PMID- 20127535
TI  - "Figure of four" position improves the visibility of the sciatic nerve in the
      popliteal fossa.
AB  - OBJECTIVES: We studied the influence of patient positioning on the visibility of
      the sciatic nerve during ultrasound (US) examination in the popliteal region.
      METHODS: Using a linear broad band 7-12 MHz frequency probe, US examination of 24
      sciatic nerves was performed by a blinded operator to obtain the best possible
      image at the level of the popliteal crease (PC) and at 4 and 8 cm above the PC in
      the prone position. Examinations were performed in neutral prone (Group N), with
      a silicone roller under the foot (Group R) and in "figure of four" (Group FOF)
      positions. "Figure of four" position was described as: the leg to be examined is
      flexed and abducted to allow the foot to rest on the ankle of the contralateral
      leg. A visibility score for the sciatic nerve was established as follows: Score
      I: Nerve is identified, but borders are not clear. Score II: Nerve is identified.
      Borders of the nerve are clearly distinguished from the surrounding structures.
      Three or less fascicles are visible. Score III: Nerve is identified. Borders of
      the nerve are clearly distinguished from the surrounding structures. Four or more
      fascicles are visible. RESULTS: The distance of nerve division from the PC was
      6.9+/-1.6 cm. A higher visibility score was obtained in Group FOF (2.6+/-0.6 vs
      1.7+/-0.8) at the PC and at 4 cm (2.3+/-0.5 vs 1.6+/-0.8) and 8 cm (2.3+/-0.7 vs
      1.4+/-0.7) above the PC, compared to Group N (p<0.001). CONCLUSION: "Figure of
      four" position improves the visibility of the sciatic nerve and may have clinical
      impact.

PMID- 20127536
TI  - [A clinic's experiences in postoperative patient controlled analgesia].
AB  - OBJECTIVES: Postoperative analgesia technique varies depending on the operation,
      patient, anesthetist, and circumstances. PCA (patient controlled analgesia) is an
      effective way of supporting postoperative analgesia. In this study, we aimed to
      present the efficacy and safety of our postoperative PCA treatment and the
      patient profile along with the requirements, preferences and decision-making
      process. METHODS: We discuss herein the PCA protocols of our clinic, the overall
      distribution of operations for which PCA was applied and the principles by which
      a pain team works. RESULTS: The operations for which PCA was applied included
      knee prosthesis, cesarean section, hip prosthesis, lower extremity trauma
      surgery, painless delivery, gastrointestinal surgery, multiple trauma surgery,
      thoracotomy, hysterectomy, laminectomy, and urogenital surgery. Postoperative PCA
      alone was successful in 89% of the patients, and with the supplemental analgesic
      agent, it was successful in an additional 6% of the patients, thus achieving a
      total success rate of 95%. CONCLUSION: We believe the epidural and intravenous
      PCA protocols applied in our clinic for postoperative analgesia are effective and
      safe.

PMID- 20127537
TI  - [The effects of lornoxicam in preventing remifentanil-induced postoperative
      hyperalgesia].
AB  - OBJECTIVES: Intraoperative remifentanil administration results in acute opioid
      tolerance that is manifested by increased postoperative pain, opioid requirement
      and specifically peri-incisional hyperalgesia. The aim of this study was to
      investigate the effect of lornoxicam in preventing remifentanil-induced
      hyperalgesia. METHODS: Patients were randomly divided into two groups. Fifteen
      minutes before surgery, saline solution was given to the patients in group I and
      16 mg i.v. Lornoxicam in group II. Anesthesia was induced with 1 microg/kg
      remifentanil combined with 1.5-2 mg/kg propofol and maintained with 0.5 MAC
      desflurane and 0.4 microg/kg/dk remifentanil in both groups. Desflurane
      concentration was titrated according to autonomic responses. All patients were
      given i.v. 0.15 mg/kg morphine 30 min before the end of surgery. At the end of
      surgery, patients received morphine i.v. Via a PCA (Patient Controlled Analgesia)
      device. Pain score, morphine demand and delivery were assessed at 2, 4, 6, 12 and
      24 h after surgery. Total morphine consumption was recorded for 24-48 h. Peri
      incisional hyperalgesia was assessed by measuring pain threshold to pressure
      using an algometer before operation and at 24-48 h postoperatively. RESULTS: The
      pain scores and cumulative morphine consumption were significantly lower in the
      lornoxicam group when compared with the control group (p<0.05). Pain thresholds
      were significantly less at 24-48 h postoperatively in the control group than in
      the lornoxicam group. No significant difference was observed in side effects
      (p>0.05). CONCLUSION: Lornoxicam administered preemptively prevented remifentanil
      induced hyperalgesia.

PMID- 20127538
TI  - [Temporal characteristics of migraine-type headache].
AB  - OBJECTIVES: Migraine is characterized by headache attacks, and symptoms belong to
      various organ systems. Temporal characteristics of headache must be known to
      prescribe the appropriate drug for the treatment of migraine attacks. In this
      study, we aimed to reveal the temporal characteristics of headache and to search
      whether or not these characteristics differ in patient subgroups in migraineurs
      admitted to a tertiary health center. METHODS: Consecutive adult migraineurs who
      admitted to the Headache Section of Kocaeli University Faculty of Medicine
      Research Hospital involved the study. Their demographical data, medical history
      and temporal characteristics of headaches were questioned. RESULTS: Thirty
      (19.6%) patients among the 153 migraineurs involved had chronic daily headache.
      Headaches were detected to reach the maximum pain intensity within 2 hours in 34
      patients (22.2%) and to continue over 24 hours in 87 (56.9%) patients. Patients
      with headaches lasting over 24 hours had a greater mean age than of those with
      headaches ending within 24 hours (40.8+/-12.4 and 36.2+/-11.4, respectively;
      p=0.019). The mean disease age of the patients with headaches lasting over 24
      hours was also greater than of the group with headaches ending within 24 hours.
      CONCLUSION: Our study revealed that temporal characteristics of headache may
      differ in patient subgroups in adult migraineurs. Further studies with large
      populations are warranted to verify these results and determine which temporal
      characteristics are common in which patient subgroups.

PMID- 20127539
TI  - [Herpes radiculopathy case presenting first with motor involvement].
AB  - Herpes zoster primarily affects the posterior root ganglions and sensorial nerve
      fibers, and causes vesicular skin eruptions, radicular pain and loss of sensorial
      function along the distribution of the affected ganglion. Motor involvement can
      also be observed. When classical cutaneous lesions are present, the motor paresis
      consequent to herpes zoster is easily diagnosed. However, diagnosis becomes
      complicated when the motor weakness is the earlier sign and precedes the
      cutaneous lesions and sensory symptoms. We present a case in whom the major
      clinical symptom and sign was the motor weakness in cervical radiculopathy
      consequent to herpes zoster.

PMID- 20127540
TI  - Emotion suppression: a preliminary experimental investigation of its immediate
      effects and role in subsequent reactivity to novel stimuli.
AB  - This study details a preliminary investigation of the subjective and
      physiological effects of emotion suppression, relative to the allowance of
      emotional experience, within one distressing situation on responses to another,
      unrelated situation. Thirty-four men were instructed to suppress or allow their
      emotional responses to a distressing film clip. Immediately following the film
      clip, participants responded to a mildly emotionally evocative interpersonal
      scenario. There was evidence of significantly different patterns of change in
      subjective distress and heart rate (HR) from one situation to the next as a
      function of whether participants received instructions to suppress or allow their
      emotional experience to the film clip. Specifically, allowance participants
      exhibited a significant decrease in subjective distress, whereas suppression
      participants exhibited no change in distress. Further, suppression participants'
      distress was significantly higher than that of allowance participants following
      the interpersonal scenario. Suppression participants also exhibited a significant
      increase in mean HR from one situation to the next, whereas allowance
      participants exhibited no change. Finally, allowance participants were
      significantly more likely to report being willing to watch the film clip again
      than were suppression participants. Results are discussed in terms of their
      implications for understanding the delayed negative consequences of emotion
      suppression.

PMID- 20127541
TI  - Structural evaluation of the contemporary psychological models of chronic pain:
      does fear of pain work for all?
AB  - The aim of the present study was to test Turk and Okifuji's (2002) model of
      chronic pain and in particular the moderating role of self-efficacy. We assessed
      207 consecutive chronic pain patients (53.1% female) on a range of relevant
      measures and tested the model using structured equation modelling. The model was
      supported. These results support Turk and Okifuji's model of chronic pain and
      suggest that it can account for the relationships between variables in chronic
      pain patients. In particular, the results support the central role of fear-based
      avoidance and self-efficacy in chronic pain. Future research should be aimed at
      testing the alternative contemporary models of chronic pain at different stages
      of the development and maintenance of chronic pain and over time.

PMID- 20127542
TI  - Subtypes of developmental dyslexia in transparent orthographies: a comment on
      Lachmann and Van Leeuwen (2008).
AB  - Lachmann and Van Leeuwen (2008) proposed two diagnostic subtypes of developmental
      dyslexia in a language with transparent orthography (German). The classification
      was based on reading time, rather than reading errors, for lists of words and
      nonwords. The two subtypes were "frequent-word reading impaired" (FWRI) and
      "nonword reading impaired" (NWRI). Notably, FWRI were very slow in reading high
      frequency words but as fast as controls in reading nonwords; ca. one-third of
      these children showed this "reversed lexicality effect" in a particularly marked
      fashion (i.e., read nonwords two to three times faster than high-frequency
      words). Since Italian is a highly transparent language, we applied this
      classification to 87 third- and sixth-grade dyslexics from various previously
      published studies. Some children showed a marked lexicality effect, while others
      showed small or no difference between word and nonword reading speed. However,
      regardless of stimulus length, grade and presence/absence of a previous language
      delay, no child showed a marked reversed lexicality effect; more generally, no
      child could be classified as FWRI. These findings indicate that the search for
      subtypes of developmental dyslexia in transparent orthographies still constitutes
      an open question.

PMID- 20127543
TI  - Selective impairment in visual short-term memory binding.
AB  - Dissociations within binding in perception have been reported after brain damage.
      In short-term memory (STM), feature binding and feature processing appear to rely
      on separate processes. However, dissociations within binding in STM following
      brain damage have not been reported to date. We report on the case E.S. who,
      after removal of a left medial sphenoid ridge meningioma, developed a selective
      impairment of visual STM (VSTM) binding. We found that, despite having normal
      perceptual binding, E.S. was unable to retain in VSTM features bound into objects
      while she could retain individual features as well as controls did (Experiments 1
      2, 4, and 6). Her verbal STM for bound and single features remains intact
      (Experiments 3 and 5). E.S.'s performance suggests that STM binding can be
      dissociated from STM for single features across visual and verbal domains. The
      results are discussed in the light of current models of STM.

PMID- 20127544
TI  - Radiolysis products and sensory properties of electron-beam-irradiated high
      barrier food-packaging films containing a buried layer of recycled low-density
      polyethylene.
AB  - The aim was to study the effect of electron-beam irradiation on the production of
      radiolysis products and sensory changes in experimental high-barrier packaging
      films composed of polyamide (PA), ethylene-vinyl alcohol (EVOH) and low-density
      polyethylene (LDPE). Films contained a middle buried layer of recycled LDPE,
      while films containing 100% virgin LDPE as the middle buried layer were taken as
      controls. Irradiation doses ranged between zero and 60 kGy. Generally, a large
      number of radiolysis products were produced during electron-beam irradiation,
      even at the lower absorbed doses of 5 and 10 kGy (approved doses for food 'cold
      pasteurization'). The quantity of radiolysis products increased with irradiation
      dose. There were no significant differences in radiolysis products identified
      between samples containing a recycled layer of LDPE and those containing virgin
      LDPE (all absorbed doses), indicating the 'functional barrier' properties of
      external virgin polymer layers. Sensory properties (mainly taste) of potable
      water were affected after contact with irradiated as low as 5 kGy packaging
      films. This effect increased with increasing irradiation dose.

PMID- 20127545
TI  - Dynamics of nitrate and nitrite content during storage of home-made and small
      scale industrially produced raw vegetable juices and their dietary intake.
AB  - The influence of storage conditions on nitrate and nitrite contents, pH, and
      total viable bacterial count of raw vegetable juices was studied. Three different
      types of juices from an Estonian small-scale producer and five different types of
      home-made juices were analysed. Analyses were performed immediately after opening
      the commercial juice packages and immediately after preparation of a home-made
      juice. Additionally, samples were taken after open storage of a juice at the
      refrigerator and ambient temperatures during 24 and 48 h. The biggest changes in
      nitrate and nitrite contents were found during storage of carrot, beetroot and
      radish juices. During 48 h of storage at ambient temperature, the mean increases
      of nitrite content in home-made carrot, beetroot and radish juices were from 0.1
      to 187, from 2.1 to 578, and from 0.5 to 259 mg l(-1), respectively. In the case
      of commercial lightly pasteurized products, the biggest increase of nitrite
      content, from 3.2 to 11 mg l(-1), was found in red beetroot juice. After 48 h of
      storage at refrigerator temperature, the changes of nitrite and nitrate were
      smaller. In the case of consumption of 300 ml of home-made carrot juice, with a
      nitrate and nitrite content of 64 and 110 mg l(-1), respectively, stored for 24 h
      at ambient temperature, the average intake was 8% and 846% of the acceptable
      daily intake of nitrates and nitrites, respectively. After consumption of 50 ml
      of the same carrot juice by children (1-2 years of age) the average intake of
      nitrates and nitrites was 7% and 733% of the acceptable daily intake,
      respectively.

PMID- 20127546
TI  - Associations of planting date, drought stress, and insects with Fusarium ear rot
      and fumonisin B1 contamination in California maize.
AB  - Fusarium ear rot, caused by Fusarium verticillioides, is one of the most common
      diseases of maize, causing yield and quality reductions and contamination of
      grain by fumonisins and other mycotoxins. Drought stress and various insects have
      been implicated as factors affecting disease severity. Field studies were
      conducted to evaluate the interactions and relative influences of drought stress,
      insect infestation, and planting date upon Fusarium ear rot severity and
      fumonisin B1 contamination. Three hybrids varying in partial resistance to
      Fusarium ear rot were sown on three planting dates and subjected to four
      irrigation regimes to induce differing levels of drought stress. A foliar-spray
      insecticide treatment was imposed to induce differing levels of insect injury.
      Populations of thrips (Frankliniella spp.), damage by corn earworm (Helicoverpa
      zeae), Fusarium ear rot symptoms, and fumonisin B1 levels were assessed. There
      were significant effects of hybrid, planting date, insecticide treatment, and
      drought stress on Fusarium ear rot symptoms and fumonisin B1 contamination, and
      these factors also had significant interacting effects. The most influential
      factors were hybrid and insecticide treatment, but their effects were influenced
      by planting date and drought stress. The more resistant hybrids and the
      insecticide-treated plots consistently had lower Fusarium ear rot severity and
      fumonisin B1 contamination. Later planting dates typically had higher thrips
      populations, more Fusarium ear rot, and higher levels of fumonisin B1. Insect
      activity was significantly correlated with disease severity and fumonisin
      contamination, and the correlations were strongest for thrips. The results of
      this study confirm the influence of thrips on Fusarium ear rot severity in
      California, USA, and also establish a strong association between thrips and
      fumonisin B1 levels.

PMID- 20127547
TI  - Age of acquisition, word frequency, and picture-word interference.
AB  - In two experiments participants named pictures superimposed with unrelated words.
      The age of acquisition (AoA) of the picture names was manipulated. Additionally,
      the word frequency (WF, Experiment 1) or AoA (Experiment 2) of the interfering
      distractor words was manipulated. Early-acquired pictures were named faster than
      their late-acquired counterparts. Both WF and AoA modulated the degree of
      interference from the irrelevant word; low-frequency and late-acquired words
      produced most interference. In neither case did the WF or AoA of the distractor
      word interact with the AoA of the picture. The results show that in the context
      of word processing both WF and AoA have similar effects.

PMID- 20127548
TI  - The use of visual context during the production of referring expressions.
AB  - Most theories of reference assume that a referent's saliency in the linguistic
      context determines the choice of referring expression. However, it is less clear
      whether cognitive factors relating to the nonlinguistic context also have an
      effect. We investigated whether visual context influences the choice of a pronoun
      over a repeated noun phrase when speakers refer back to a referent in a preceding
      sentence. In Experiment 1, linguistic mention as well as visual presence of a
      competitor with the same gender as the referent resulted in fewer pronouns for
      the referent, suggesting that both linguistic and visual context determined the
      choice of referring expression. Experiment 2 showed that even when the competitor
      had a different gender from the referent, its visual presence reduced pronoun
      use, indicating that visual context plays a role even if the use of a pronoun is
      unambiguous. Thus, both linguistic and nonlinguistic information affect the
      choice of referring expression.

PMID- 20127549
TI  - American Society of Hematology--51st annual meeting & exposition. Part 1.
AB  - The 51st American Society of Hematology (ASH) Annual Meeting and Exposition, held
      in New Orleans, included topics covering new therapeutic developments in the
      field of hematology. This conference report highlights selected presentations on
      hematological malignancies, lymphoma, Hodgkin lymphoma, AKT inhibitors for the
      treatment of chronic lymphocytic leukemia, and the activation of GPIb with von
      Willebrand factor. Investigational drugs discussed include conatumumab (Amgen
      Inc/Takeda Bio Development Center Ltd) and A-443654 (Abbott Laboratories).

PMID- 20127550
TI  - American Society of Hematology--51st annual meeting & exposition. Part 2.
AB  - The 51st Annual Meeting & Exposition of the American Society of Hematology, held
      in New Orleans, included topics covering new therapeutic developments in the
      field of hematology. This conference report highlights selected presentations on
      combination regimens for the treatment of multiple myeloma, selected kinase
      inhibitors and a recombinant HOXB4 protein. Investigational drugs discussed
      include SB-1518 (S*Bio Pte Ltd) and PF-2341066 (Pfizer Inc).

PMID- 20127551
TI  - European Society of Gene & Cell Therapy--17th annual congress.
AB  - The 17th Annual Congress of the European Society of Gene & Cell Therapy, held in
      Hanover, Germany, included topics covering new developments in the field of stem
      cell therapy. This conference report highlights selected presentations on stem
      cell gene therapy and the use of stem cells in regenerative medicine.
      Investigational therapies discussed include Lenti-D (Genetix Pharmaceuticals
      Inc/INSERM) and LentiGlobin (Genetix), a lentiviral vector-based gene transfer
      system containing either a human beta-globin gene or a hybrid A-gamma/beta-globin
      gene.

PMID- 20127552
TI  - Clinical trials in CNS--SMi's eighth annual conference.
AB  - The SMi's Eighth Annual Conference on Clinical Trials in CNS, held in London,
      included topics covering new therapeutic developments in the field of CNS
      disorders. This conference report highlights selected presentations on emerging
      clinical targets for the treatment of Alzheimer's disease, achievements of the
      Alzheimer's Disease Neuroimaging Initiative, computational assessment methods
      applicable to Alzheimer's disease and to the monitoring of suicidality, the
      accelerated antidepressive effect of PNB-01 (PharmaNeuroBoost NV; comprising a
      combination of pipamperone and citalopram), and clinical trials in amyotrophic
      lateral sclerosis and spinal muscular atrophy. Investigational drugs discussed
      also include begacestat (Pfizer Inc) and olesoxime (Trophos SA).

PMID- 20127553
TI  - The role of natural products in drug discovery and development in the new
      millennium.
AB  - The role of Natural Products in Drug Discovery and development in the New
      Millennium meeting, held in London, included topics covering new developments in
      the field of natural products in drug discovery. This conference report
      highlights selected presentations on the value of natural products, natural
      product screening opportunities and technological improvements to enhance the use
      of natural compounds in drug discovery and development.

PMID- 20127554
TI  - Gene-BIT Life Sciences' third annual world congress. Anti-neurodegenerative and
      anti-inflammation biotherapeutics.
AB  - The BIT Life Sciences' Third Annual World Congress of Gene, held in Sanshui,
      China, included topics covering new developments in the field of gene-based
      therapeutic approaches and target identification. This conference report
      highlights selected presentations on aspirin-triggered lipoxins for inflammation,
      hepatocyte nuclear factor HNF4alpha as a target for intestinal inflammation, P2Y
      nucleotide receptor antagonism for inflammatory diseases, antioxidant approaches
      for hearing loss prevention, targeting protein kinase CK2 in neuronal injury, the
      role of AATF (apoptosis antagonizing transcription factor)-mediated
      neuroprotection in Alzheimer's disease, and lessons from bioactive proteins from
      plants.

PMID- 20127555
TI  - Terrapinn's world influenza congress Europe 2009. Part 1.
AB  - Terrapinn's World Influenza Congress Europe 2009, held in Brussels, included
      discussions of the current status of influenza worldwide. This conference report
      highlights selected presentations on the response to the H1N1 influenza pandemic,
      future strategies for combating pandemic influenza, and the role of novel vaccine
      technology in the pandemic response. Investigational vaccines discussed include
      M2del11HAavir H1N1 and M2del11HAavir H5N1 (FluGen Inc).

PMID- 20127556
TI  - Terrapinn's world influenza congress Europe 2009. Part 2.
AB  - Terrapinn's World Influenza Congress Europe 2009, held in Brussels, included
      topics covering new developments in the field of influenza vaccination. This
      conference report highlights selected presentations on the use of novel
      technologies for developing vaccines for influenza. Investigational vaccines
      discussed include Multimeric-001 (BiondVax Pharmaceuticals Ltd), NB-1008 (NanoBio
      Corp) and an influenza vaccine containing the CAF-01 adjuvant (Statens Serum
      Institut).

PMID- 20127557
TI  - San Antonio breast cancer symposium--32nd annual meeting.
AB  - The 32nd San Antonio Breast Cancer Symposium, held in San Antonio, TX, USA,
      included topics covering etiology, epidemiology and tumor immunotherapy in the
      field of breast cancer therapy. This conference report discusses epigenetics and
      the PI3K/Akt/mTOR pathway in breast tumorigenesis.

PMID- 20127558
TI  - Parkinson's disease and related disorders--XVIII WFN World Congress.
AB  - The XVIII World Federation of Neurology (WFN) World Congress on Parkinson's
      Disease and Related Disorders, held in Miami, FL, USA, included topics covering
      new therapeutic developments in this field. This conference report highlights
      selected presentations on the pathophysiology and treatment of these diseases,
      including the design of neuroprotective compounds, protein inhibition in the
      absence of catechol-O-methyltransferase (COMT), evaluating the striatal
      distribution of COMT, clinical results for PYM-50028 (Phytopharm plc) and
      ProSavin, and research into the use of stem cell treatments for Parkinson's
      disease.

PMID- 20127559
TI  - Improving drug safety using computational biology.
AB  - Despite the significant investment made in drug safety testing by the
      pharmaceutical industry, new drugs continue to experience a substantial failure
      rate because of unacceptable toxicology in patients. More effective methods of
      predicting potential safety issues that can be employed during the drug design
      phase are required to reduce this attrition. Computational biology offers such
      new approaches, and is a term that includes a wide range of disciplines, the
      general features of which are the application of computer science and mathematics
      to biology. The techniques used in computational biology can integrate and
      analyze large complex sets of data and enable scientists to truly exploit the
      large amounts of information available to them, both in predicting likely risk
      and in understanding issues when they arise. These new approaches can only be
      achieved by embracing in silico experimentation as a valid and equal partner to
      other forms of experimentation in drug safety, and by integrating these
      approaches alongside current methods to support better decision-making in R&D
      that will ultimately result in the production of safer medicines.

PMID- 20127560
TI  - Emerging trends in ion channel-based assays for predicting the cardiac safety of
      drugs.
AB  - Regulators require prospective new drugs to be tested for potential cardiac
      effects that are relevant to drug safety. As a result, numerous technologies have
      been developed to screen drugs for off-target effects that compromise the
      function of hERG potassium channels, which are associated with acquired long QT
      syndrome - a disorder with a risk of sudden death as a result of arrhythmia.
      Automated patch clamp, which is the most important and commonly used technology
      for the preclinical assessment of the risk of arrhythmia, continues to evolve
      toward greater sophistication, higher success rates and increased ease of use.
      Patch clamp advances include the development of population patch clamp and the
      ability to make more consistent measurements from freshly thawed prevalidated
      cells. Nevertheless, several discrepancies between hERG testing, QT prolongation
      and the risk of arrhythmia have been well-publicized. As a result, ion channel
      screening has been further developed to enable the assaying of currents from a
      wider variety of cardiac ion channels and the measurement of action potentials
      from stem cell-derived cardiomyocyte-like cells. Emerging measurement
      technologies beyond patch clamp include the measurement of field potentials with
      multi-electrode arrays.

PMID- 20127561
TI  - Applying a gaming approach to IP strategy.
AB  - Adopting an appropriate IP strategy is an important but complex area,
      particularly in the pharmaceutical and biotechnology sectors, in which aspects
      such as regulatory submissions, high competitive activity, and public health and
      safety information requirements limit the amount of information that can be
      protected effectively through secrecy. As a result, and considering the existing
      time limits for patent protection, decisions on how to approach IP in these
      sectors must be made with knowledge of the options and consequences of IP
      positioning. Because of the specialized nature of IP, it is necessary to impart
      knowledge regarding the options and impact of IP to decision-makers, whether at
      the level of inventors, marketers or strategic business managers. This feature
      review provides some insight on IP strategy, with a focus on the use of a new
      'gaming' approach for transferring the skills and understanding needed to make
      informed IP-related decisions; the game Patentopolis is discussed as an example
      of such an approach. Patentopolis involves interactive activities with IP-related
      business decisions, including the exploitation and enforcement of IP rights, and
      can be used to gain knowledge on the impact of adopting different IP strategies.

PMID- 20127562
TI  - Lomitapide, a microsomal triglyceride transfer protein inhibitor for the
      treatment of hypercholesterolemia.
AB  - New lipid-lowering agents include microsomal triglyceride transfer protein (MTP)
      inhibitors, which may have a role in the treatment of hypercholesterolemia.
      Clinical applications of MTP inhibitors have been focused primarily on high-dose
      monotherapy to produce substantial reductions in LDL-cholesterol levels
      (particularly for patients with homozygous familial hypercholesterolemia).
      However, this strategy has been associated with a high rate and severity of
      gastrointestinal and hepatic adverse events that has prohibited the use of these
      agents. Data suggest the LDL-cholesterol-lowering efficacy of low-dose lomitapide
      (AEGR-733, formerly BMS-201038), under development by Aegerion Pharmaceuticals
      Inc, in patients with familial hypercholesterolemia, both as a single agent and
      in combination with commonly prescribed lipid-lowering therapies. MTP inhibition
      with lomitapide may offer a treatment option for patients who cannot tolerate
      statin therapy or who experience insufficient LDL-cholesterol reduction with
      available therapies. However, the safety concerns for MTP inhibitors for the
      treatment of hyperlipidemia must be fully addressed, and the assessment of the
      risk-to-benefit ratio for MTP inhibitors in patients at different levels of
      cardiovascular-disease risk is required before clinical use of this class of
      drugs may be recommended.

PMID- 20127564
TI  - New dress on an old pig? ACOs tie payment to accountability, outcomes.
AB  - Some physicians, hospital executives, and health care policy analysts are pushing
      accountable care organizations (ACOs) to replace fee-for-service medicine. In an
      ACO, physicians and other health care professionals have financial incentives to
      contain costs and improve quality by coordinating care for a specific group of
      patients. Hospitals, physicians, and other health care professionals in the
      organization share the savings.

PMID- 20127563
TI  - XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid
      cancer, glioblastoma multiforme and NSCLC.
AB  - XL-184 (BMS-907351), under development by Exelixis Inc and Bristol-Myers Squibb
      Co, is a pan-tyrosine kinase inhibitor for the potential oral treatment of
      medullary thyroid cancer, glioblastoma multiforme and NSCLC. The prinicipal
      targets of XL-184 are MET, VEGFR-2 and RET, but the drug is also reported to
      display inhibitory activity against KIT, FLT3 and TEK. Preclinical studies
      demonstrated that XL-184 potently inhibited multiple receptor tyrosine kinases in
      various cancer cell lines and animal xenograft models, and that the drug
      exhibited significant oral bioavailability and blood-brain barrier penetration. A
      phase I clinical trial in patients with advanced solid malignancies indicated
      that XL-184 accumulated dose-dependently in the plasma and had a long terminal
      half-life. A phase II trial in patients with progressive or recurrent
      glioblastoma revealed modest but promising median progression-free survival.
      Toxicity and side effects for the drug have generally been of low-to-moderate
      severity. At the time of publication, three additional trials of XL-184 were
      recruiting patients, including a phase I trial in combination with standard of
      care in patients with glioblastoma, a phase I/II trial in combination with
      erlotinib in patients with NSCLC, and a phase III trial in patients with
      medullary thyroid cancer.

PMID- 20127565
TI  - Mammogram mania: task force screening recommendation creates chaos.
AB  - After the U.S. Preventive Services Task Force updated its screening mammography
      recommendations last November, it received criticism and scrutiny from the
      medical community and breast cancer prevention and treatment advocates and
      organizations.

PMID- 20127566
TI  - Cocoon of health: physicians try cocooning against williamson county pertussis.
AB  - Williamson county--just north of Austin--is in the midst of a full-blown
      pertussis outbreak that has physicians, public health officials, and other health
      care professionals fighting its spread and trying to save children's lives with a
      relatively new tactic called "cocooning." The strategy protects tiny,
      unvaccinated infants by encouraging Tdap immunizations among all adults and
      children who have close contact with newborns.

PMID- 20127567
TI  - Building on a commitment: new housing, education center a model for rural medical
      training.
AB  - The East Texas community of Crockett showed its growing commitment to medical
      education earlier this year when it launched construction of a Rural Physicians
      Education Center to provide housing for Texas College of Osteopathic Medicine
      students and family medicine residents from the Texas A&M Health Science Center
      doing one- to two-month rotations.

PMID- 20127568
TI  - Too Much Discretion: TMA Supports Banning Insurance Discretionary Clause.
AB  - The Texas Office of Public Insurance Counsel, the Texas Medical Association, the
      American Heart Association, AARP, the National Multiple Sclerosis Society, and a
      Texas physician-lawmaker are upset about insurers' use of discretionary clauses.
      Such clauses give the companies free rein to interpret policy terms and evaluate
      a patient's claim for benefits however they choose.

PMID- 20127569
TI  - Have we understood diabetes? New tasks for diagnosis and therapy.
AB  - Recently published data examining the role of the metabolic syndrome and obesity
      in cardiovascular disease rendered surprising results. In addition, other studies
      revealed that there is more to diabetes therapy than lowering blood glucose,
      which might under certain circumstances even harm patients. In the light that we
      now know that "death" is as important an endpoint in diabetes as in other
      diseases, new tools--better than the oral glucose tolerance test--are required to
      identify the patients at risk, as are additional standards in individualized
      therapy. A critical view on old concepts is necessary.

PMID- 20127570
TI  - Diabetes mellitus type 2 - an independent risk factor for cancer?
AB  - Epidemiological findings have shown up to two-fold increases in the risks of
      cancers of the colorectum, breast, endometrium, kidney (renal cell tumours),
      liver and pancreas among diabetes patients. In the present review, we address the
      question whether, on the basis of these epidemiological observations, type 2
      diabetes should be considered a specific and independent risk factor for these
      various forms of cancer, due to its particular metabolic characteristics of
      glucose intolerance and hyperinsulinemia. On the basis of further epidemiological
      evidence among non-diabetic individuals, as well as recent studies examining the
      effects of different types of diabetes treatment on cancer risks, we conclude
      that chronic elevations in fasting and non-fasting blood levels of glucose and/or
      insulin are plausible independent risk factors for cancer, but that much of the
      increase in cancer risks associated with these two metabolic factors may occur
      within the normoglycaemic and insulinemic (non-diabetic) ranges. Furthermore, for
      some tumour types (e. g. cancer of the endometrium) the associations of risk with
      type 2 diabetes may to a large extent be due to, and at least partially
      confounded by, other obesity-related alterations in (e. g. sex steroid)
      metabolism that in part are independent of glucose and/or insulin metabolism.
      Specifically for pancreatic cancer, a major question, addressed in detail by
      other reviews, is whether associations of risk with plasma glucose, insulin or
      overt type 2 diabetes could be either a cause, or possibly also a consequence of
      tumour development (or both).

PMID- 20127571
TI  - Concerning the article "Cushing's disease associated with both pituitary
      microadenoma and corticotroph hyperplasia".

PMID- 20127572
TI  - Stephen G. Reich.

PMID- 20127573
TI  - Neurologic pearls.

PMID- 20127574
TI  - Pearls: primary brain tumors.
AB  - Most physicians in general, and neurologists in particular, enjoy tackling
      challenging clinical cases; making the correct diagnosis can be quite satisfying.
      However, primary brain tumors may present with nonspecific or subtle signs that
      can sometimes be missed or misinterpreted. More than ever, brain imaging has
      improved our ability to correctly diagnose and care for patients with brain
      tumors. We have included some cases from the Department of Neurology at Memorial
      Sloan-Kettering Cancer Center (New York, NY) to help illustrate some "pearls"
      when considering the diagnostic possibility of a brain tumor.

PMID- 20127575
TI  - Pearls: parkinsonism.
AB  - Diagnosing Parkinson's disease and distinguishing it from other forms of
      parkinsonism are primarily based on clinical features. These conditions may
      present with nonspecific symptoms that are not obviously neurologic (e.g.,
      fatigue, depression, insomnia, pain, stiffness). Many subtle clues provided by
      history and examination are crucial, with laboratory and imaging being primarily
      supportive.

PMID- 20127576
TI  - Pearls: hyperkinetic movement disorders.
AB  - Hyperkinetic movement disorders are characterized by an excessive degree of
      involuntary motor activity and are classified by their clinical phenomenology.
      The five major categories include tremor, dystonia, chorea and ballismus, tics,
      and myoclonus. This article presents a series of "pearls" for each category of
      movements, emphasizing the recognition of common disorders as well as rare, but
      treatable hyperkinesias. In addition to the major categories, clinical pearls
      also cover drug-induced movement disorders and psychogenic movement disorders.

PMID- 20127577
TI  - Pearls: dizziness.
AB  - Contrary to common belief, making a diagnosis in the patient with dizziness can
      be relatively straightforward. To do so, the clinician must be aware of the
      pitfalls in taking a history from the dizzy patient as well as be familiar with
      specific examination techniques, such as the Hallpike maneuver and the head
      thrust test. We summarize the important aspects of history taking and examination
      in the dizzy patient and relate these clinical aspects to the most common
      diagnoses that cause patients to complain of dizziness.

PMID- 20127578
TI  - Pearls: neuromuscular disorders.
AB  - Various brief clinical observations helpful in the evaluation of patients with
      neuromuscular disorders are discussed and illustrated. These include features of
      focal neuropathies, including the neurologic thoracic outlet syndrome, apparent
      ulnar nerve-innervated hand weakness in radial neuropathies, scapula movement in
      long thoracic compared with spinal accessory neuropathies, and diaphragm
      paralysis in segmental zoster paresis. Potential diagnostic errors include
      multifocal motor neuropathy mistaken for nerve tumor, the pseudoconduction block
      of vasculitic neuropathy leading to a diagnosis of Guillain-Barre syndrome, and
      leg paralysis in myelopathy mistaken for early ascending paralysis in Guillain
      Barre syndrome. Very focal weakness of limb muscles occurs in myasthenia gravis,
      similar to the more familiar focal cranial muscle involvement. Fluctuation, not
      fatigability, in myasthenia gravis is discussed. The presentation of Lambert
      Eaton myasthenic syndrome as a nonfluctuating subacute myopathy is emphasized.
      Patterns of weakness in inclusion body myositis and facioscapulohumeral muscular
      dystrophy are illustrated.

PMID- 20127579
TI  - Pearls: myasthenia.
AB  - Myasthenia gravis is typically an acquired autoimmune disorder in which
      antibodies are directed at structural components of the neuromuscular junction,
      most commonly the nicotinic acetylcholine receptor. The clinical manifestations
      of skeletal muscle weakness are broad. Patients most often report fatigable
      muscle weakness. The eyelid levators and extraocular muscles are most commonly
      affected, resulting in symptoms of ptosis and diplopia. Symptoms may be confined
      to the eyes (ocular myasthenia) or reflect bulbar, limb, or respiratory muscle
      weakness (generalized myasthenia). The diagnosis is based on a characteristic
      history and the finding of fatigable muscle weakness on examination, and may be
      supported by diagnostic tests such as finding elevated titers of acetylcholine
      receptor or muscle-specific receptor tyrosine kinase (MuSK) antibodies, a
      positive Tensilon test, a decremental response on slow repetitive nerve
      stimulation, and abnormal jitter on single fiber electromyography. This article
      presents a series of pearls to aid in the clinical and laboratory diagnosis of
      myasthenia gravis, emphasizing key historical features, common and characteristic
      findings on examination, and potential pitfalls in the use of ancillary
      diagnostic studies.

PMID- 20127580
TI  - Pearls: myelopathy.
AB  - Both general neurologists and neurologists with a broad spectrum of subspecialty
      interests are often asked to evaluate patients with disorders of the spinal cord.
      Over the past decade, there have been significant advances in our understanding
      of a wide spectrum of immune-mediated, infectious, metabolic, hereditary,
      paraneoplastic, and compressive myelopathies. Advances have been made in the
      classification and management of spinal vascular malformations. Aortic
      reconstruction surgery has led to an increased incidence of spinal cord stroke.
      It is important to recognize a dural arteriovenous fistula as a cause of
      progressive myelopathy. In the past, noninfectious inflammatory myelopathies have
      frequently been categorized as idiopathic transverse myelitis. Advances in
      neuroimaging and discovery of a serum antibody marker, neuromyelitis optica
      immunoglobulin G (NMO-IgG), have allowed more specific diagnoses, such as
      multiple sclerosis and neuromyelitis optica. Abnormalities suggestive of
      demyelinating disease on brain magnetic resonance imaging (MRI) are known to be
      highly predictive of conversion to multiple sclerosis in a patient who presents
      with a transverse myelitis ("clinically isolated syndrome"). Acquired copper
      deficiency can cause a clinical picture that mimics the subacute combined
      degeneration seen with vitamin B (12) deficiency. A history of bariatric surgery
      is commonly noted in patients with copper deficiency myelopathy. Genetics has
      advanced our understanding of the complex field of hereditary myelopathies. Three
      hereditary myelopathy phenotypes are recognized: predominantly cerebellar (e.g.,
      Friedreich's ataxia), predominantly motor (e.g., hereditary spastic paraparesis),
      and a leukodystrophy phenotype (e.g., adrenomyeloneuropathy). Evaluation of
      myelopathies when no abnormalities are seen on spinal cord imaging is a commonly
      encountered diagnostic challenge. This article presents some "clinical pearls" in
      the evaluation and management of spinal cord diseases in context of these recent
      developments.

PMID- 20127581
TI  - Pearls: visual loss.
AB  - The clinician who is evaluating a patient with visual loss faces a large initial
      differential diagnosis. By taking a systematic approach to the history of the
      present illness, including reviewing systems, examination, and subsequent
      testing, several potential pitfalls will be avoided, and a brief differential
      diagnosis list can be generated. This article uses illustrative cases to present
      a variety of history, examination, and testing pearls for diagnosing the source
      of visual loss.

PMID- 20127582
TI  - Pearls: nystagmus.
AB  - Nystagmus is a spontaneous, repetitive movement of the eyes caused by slow eye
      drifts. Clinical evaluation of nystagmus requires familiarity with the functional
      classes of eye movements, the types of acquired nystagmus and a differential
      diagnosis for each type, and the ability to differentiate acquired nystagmus from
      infantile nystagmus and saccadic intrusions.

PMID- 20127583
TI  - Pearls: diplopia.
AB  - Double vision may arise from ocular, neurologic, or extraocular muscle disorders.
      The approach to patients with diplopia requires a systematic approach to the
      history and the physical examination. There are many challenges in the evaluation
      of diplopia, ranging from the patient's mental status to the fine points of the
      examination. This article provides a process for interviewing and examining these
      patients, explaining the rationale and differential diagnosis of various clinical
      presentations. Common causes of monocular and binocular diplopia are addressed by
      the pattern of diplopia described by the patient. The examination and the
      interpretation of examination findings are presented by incorporating the "upside
      down-and-backwards" concept. This review offers some Pearls-perhaps even diamonds
      on evaluating patients who complain of diplopia, as well as those who have eye
      movement abnormalities but can't articulate their symptoms.

PMID- 20127584
TI  - Pearls: neurologic complications of HIV/AIDS.
AB  - Clinically apparent and frequently debilitating neurologic disease is common with
      infection by HIV type 1. Approximately one half of all HIV-infected patients will
      develop clinically significant neurologic disease, and the frequency with which
      neuropathologic abnormalities are detected at autopsy in some series exceeds 90%,
      suggesting that neurologic findings are often overlooked. Not surprisingly,
      careful neurologic examination, even in the absence of specific complaints by the
      HIV-infected patient, often reveals evidence of central or peripheral nervous
      system dysfunction. Although neurologic disease typically occurs with advanced
      disease and profound immunosuppression, it may also occur during early stages of
      the infection. In as many as 20% of individuals, neurologic disease is the
      harbinger of AIDS. The spectrum of neurologic disorders that complicate HIV
      infection is extremely broad; any part of the neuraxis may be affected.
      Additionally, the complexity of evaluating the HIV-infected person with
      neurologic disease is increased by the relatively high frequency with which more
      than one disease concurrently affects the nervous system.

PMID- 20127585
TI  - Pearls: infectious diseases.
AB  - Neurologists have a great deal of knowledge of the classic signs of central
      nervous system infectious diseases. After years of taking care of patients with
      infectious diseases, several symptoms, signs, and cerebrospinal fluid
      abnormalities have been identified that are helpful time and time again in
      determining the etiological agent. These lessons, learned at the bedside, are
      reviewed in this article.

PMID- 20127586
TI  - Pearls: headache.
AB  - Distinguishing primary headache from secondary headache is the first objective of
      every new clinical encounter with a patient complaining of headache. The history
      is king in headache medicine-90% of patients presenting with headache have a
      primary headache disorder and the examination is normal. The history must be
      elicited because patients will not always volunteer seminal information. A
      standard series of questions must be asked of each patient to guide an
      appropriate diagnostic evaluation and ensure that secondary causes are not
      overlooked. The second objective, of course, is making the correct diagnosis of
      the primary headache disorder. Although at first glance this appears obvious and
      almost patronizing, making the correct diagnosis is often not a priority, nor is
      it a process that is emphasized in undergraduate and postgraduate training
      programs. Knowing some simple rules and standard questions will make the process
      almost fail proof.

PMID- 20127587
TI  - Pearls: epilepsy.
AB  - Technology plays a greater and expanding role in the evaluation, diagnosis, and
      treatment of epilepsy and seizure disorders with the use of
      electroencephalography and video electroencephalography (EEG) monitoring.
      However, the history and clinical examination of the patient will always be the
      most important parts of the evaluation of patients with seizures, epilepsy, and
      other similar disorders. Clinical pearls for the differential diagnosis of
      seizures, psychogenic nonepileptic seizures, initial diagnosis of epilepsy,
      epilepsy evaluation, and use of anticonvulsants are provided.

PMID- 20127588
TI  - Pearls: stroke.
AB  - The diagnosis of ischemic stroke continues to be a clinical one, although
      advances in neuroimaging have expanded our understanding of the correlation
      between clinical symptoms and neuroanatomical localization. Careful neurologic
      examination allows localization in both neuroanatomical and vascular space.
      Findings on neuroimaging are then correlated to assess their clinical relevance.
      Transient ischemic attack is recognized as a warning sign for impending vascular
      disease, but even less specific transient neurologic symptoms are associated with
      increased risk. Stroke can occur at any age. For women, the postpartum period is
      a time of elevated risk for arterial ischemic stroke.

PMID- 20127589
TI  - Pearls: sleep disorders.
AB  - Sleep disorders and sleep complaints are common in the neurology patient. A good
      history can often be started with just a few well-worded questions to help
      identify the major sleep disorders. Identifying sleep-related disorders can help
      the neurologist broaden the differential diagnosis and treat disorders that can
      contribute significantly to many comorbidities of other neurologic diseases.

PMID- 20127590
TI  - Pearls: multiple sclerosis.
AB  - Multiple sclerosis (MS) affects more than 500,000 Americans, and it is commonly
      on the differential diagnosis associated with patient referrals to neurology
      offices. Diagnostically, there are several nuances to the established criteria.
      Understanding the usefulness of various tests and the potential diagnoses that
      can cause false-positives is critical when evaluating patients for possible MS.
      Furthermore, recognizing various possible mimics in given situations will help
      practitioners avoid unnecessary treatment of patients. Once diagnosed, MS
      patients have a multitude of possible symptoms that they can experience, and rely
      on their neurologists to have an understanding of the potential interventions.
      Finally, there are various therapies currently available for disease
      modification. Developing a reasonable treatment algorithm that can be applied to
      patients is important when presenting patients with the various options. This
      article summarizes some of the pearls and pitfalls associated with the evaluation
      and management of patients with relapsing-remitting multiple sclerosis.

PMID- 20127591
TI  - Glioblastoma invasion, cathepsin B, and the potential for both to be inhibited by
      auranofin, an old anti-rheumatoid arthritis drug.

PMID- 20127592
TI  - Primary optic nerve sheath meningiomas: a follow-up study.
AB  - OBJECTIVE: The management of optic nerve sheath meningiomas (ONSM) remains
      controversial, but includes surgery, radiotherapy and plain observation. We
      present a follow-up study and treatment modalities based on our classification
      system. PATIENTS AND METHODS: A retrospective analysis was performed of 90
      patients with optic nerve sheath meningiomas who were treated between 1991 and
      2008 (n=65 surgery only, n=5 radiation only, n=18 surgery and postoperative
      radiation, n=2 observation). Follow-up data was available, ranging from 6 to 220
      months with a median of 45.8 months. RESULTS: Our classification system
      differentiates between intraorbital (type 1), intracanalicular or intrafissural
      (type 2), and intraorbital and intracranial (type 3) ONSMs. Thirty-seven tumors
      demonstrated extension through the optic canal (type 2a). 41 further tumors
      reached the chiasm (type 3a) or contralateral side (type 3b). Visual acuity was
      not significantly influenced by surgery but did become worse with a longer
      duration of preoperative symptoms and a longer follow-up period. Radiotherapy
      improved vision in 4 and preserved vision in 16 out of 23 cases. CONCLUSIONS:
      Loss of vision in optic nerve sheath meningiomas is a question of time.
      Radiotherapy should be offered for intraorbital ONSM. Surgery with decompression
      of the optic canal and intracranial tumor resection is still favored for tumors
      with intracanalicular and intracranial extension.

PMID- 20127593
TI  - [The use of mamma MRI volumetry to evaluate the rate of fat survival after
      autologous lipotransfer].
AB  - INTRODUCTION: Autologous lipotransfer is becoming more and more popular in
      plastic surgery. Until now the rate of fat survival was merely estimated by the
      surgeon and no proven data exist. To assess this surgical method a reproducible
      and exact tool for volume analysis is necessary. PATIENTS AND METHODS: The volume
      of silicone implants was calculated in six healthy patients with silicone breast
      augmentation using the BrainLab(c) I Plan Software. In the same technique
      volumetry was performed in 10 patients before and six months after autologous
      lipotransfer using the water-jet assisted liposuction (BEAULI) to harvest the fat
      tissue. RESULTS: Comparison of the implant volumes calculated with MRI volumetry
      with the official volumes given by the manufacturer showed a very low mean
      deviation of 2.1+/-1.5%. Preoperative and postoperative MRI volumetry in patients
      after autologous lipotransfer revealed a mean volume augmentation of 147+/-18 mL.
      In these patients 72+/-11% of the transplanted fat tissue persisted in the area
      of injection six month after surgery. CONCLUSION: MRI volumetry is a useful tool
      for the fast, exact and reproducible volume analysis of breast tissue. Especially
      after autologous lipotransfer, where MRI examinations are performed on a regular
      basis to exclude possible complications, the use of these data to evaluate the
      rate of fat tissue survival is appealing and due to the high exactness of the
      method also reasonable.

PMID- 20127594
TI  - [Oesophageal perforation: a retrospective analysis of aetiology, diagnosis and
      therapy].
AB  - Oesophageal perforation is commonly a rare diagnosis which is associated with a
      high mortality rate. Decisive for a good clinical outcome are localisation and
      depth of the perforation, risk factors, the time until diagnosis and a rapid
      therapy. The data we collected agree with those in the published papers. In cases
      of an early diagnosis sometimes an endoscopic therapy is possible. In -cases of
      surgical therapy the smallest intervention is the most favourable. A resection
      with the necessity for a later reconstruction is considered as the ultima ratio.

PMID- 20127595
TI  - Oculogyric crisis with sertindole monotherapy.

PMID- 20127596
TI  - Panic attack after spice abuse in a patient with ADHD.

PMID- 20127597
TI  - Developing and executing a strategic plan.
AB  - Because of the historic economic crisis, the past 18 months--2008 and the first
      half of 2009--have been challenging for many plastic surgery practices. Prior to
      the economic crisis in 2008, many practices enjoyed success with little
      synchronization between financial and productivity results, practice goals, and
      strategic planning. Now, suddenly, there is a great deal of interest in the
      alignment of budgets and financial reporting, marketing return on investment
      (ROI), staff accountability, and overhead management. The process of developing a
      business plan can serve to bring clarity and objectivity to the assessment of
      practice goals and market dynamics. The business planning process also provides
      assurance of more efficient use of the practice's human and capital resources.
      Ultimately, the process will bring order, discipline, and focus to practice
      stakeholders, thus increasing the likelihood of meeting or exceeding practice
      goals. The process: (1) defining the mission of the practice; (2) completing a
      competitive analysis for your market; (3) completing an assessment of your
      current environment; (4) completing an assessment of the financial health of your
      practice; (5) preparation of a SWOT (strengths, weakness, opportunity, threat)
      analysis; and (6) a translation of your mission statement into specific long-term
      goals and short-term performance objectives. The outcome of completing these
      tasks should be an actionable plan that will serve as a guide or road map for the
      practice. A well-articulated plan will solidify staff confidence, continue the
      advancement of a strong business foundation, and provide clear navigation through
      this new economic landscape in a way that preserves your ability to provide the
      care you have devoted yourselves to deliver. Today's needs, and yesterday's
      lessons, dictate that a well-documented strategic action plan be undertaken.

PMID- 20127598
TI  - How to create high-performing teams.
AB  - This article is intended to discuss inspirational aspects on how to lead a high
      performance team. Cogent topics discussed include how to hire staff through
      methods of "topgrading" with reference to Geoff Smart and "getting the right
      people on the bus" referencing Jim Collins' work. In addition, once the staff is
      hired, this article covers how to separate the "eagles from the ducks" and how to
      inspire one's staff by creating the right culture with suggestions for further
      reading by Don Miguel Ruiz (The four agreements) and John Maxwell (21 Irrefutable
      laws of leadership). In addition, Simon Sinek's concept of "Start with Why" is
      elaborated to help a leader know what the core element should be with any
      superior culture.

PMID- 20127599
TI  - [Localisation of hepatic lesions to liver segments according to sonography (US),
      computed tomography (CT) and surgery (OP): a comparative study].
AB  - INTRODUCTION: The localisation of focal liver lesions is usually performed
      according to the Couinaud classification system. The exact description of
      localisation and size of liver lesions is especially important for surgical
      procedures. The aim of this prospective study was the evaluation of differences
      and agreements in the localisation and size of hepatic lesions as found by
      ultrasound (US), computed tomography (CT) and according to the intraoperative
      status (OP). MATERIAL AND METHODS: 32 patients (21 male, 11 female) were enrolled
      in the study. The results obtained from sonography, computed tomography and
      surgery were classified into 5 categories for localisation and for size,
      respectively. RESULTS: According to the agreement between sonography and computed
      tomography, 25 % of all hepatic lesions were classified into category 1 (exact
      agreement), whereas 40.6 % were ranked into category 2 (almost exact agreement).
      Correlating sonography and intraoperative results, 31.3 % of the lesions were
      classified into category 1 and 46.9 % into category 2. In the comparison of CT
      with OP, 34.4 % of the lesions were found to be in category 1 and 43.8 % in
      category 2. Concerning the size of the lesions, almost half of the tumours (46.9
      %) were classified into category 1 on the basis of the correlation between US and
      CT and 21.9 % on the basis of the correlation between US and OP. DISCUSSION: The
      localisation and description of the size of hepatic lesions is mainly similar or
      even identical on the basis of the different methods. Further improvements might
      be achieved by the introduction of a consistent nomenclature.

PMID- 20127600
TI  - Medical and endoscopic treatment in peptic ulcer bleeding: a national German
      survey.
AB  - OBJECTIVE: Peptic ulcers are the leading cause of upper gastrointestinal (GI)
      bleeding. The aim of this study was the evaluation of the recent clinical
      practice in drug therapy and endoscopic treatment of ulcer bleedings in Germany
      and to compare the results with the medical standard. METHODS: A structured
      questionnaire (cross-sectional study) was sent to 1371 German hospitals that
      provide an emergency service for upper GI bleeding. The project was designed
      similar to a nationwide inquiry in France in 2001. Forty-four questions
      concerning the following topics were asked: hospital organisation, organisation
      of emergency endoscopy service, endoscopic and drug therapy of ulcer bleeding,
      endoscopic treatment of variceal bleeding. Return of the questionnaires was
      closed in August 2004. RESULTS: Response rate was 675 / 1371 (49 %). Mean
      hospitals size was < 200 beds, 49 % (n = 325) had basic care level. 92 % provided
      a 24-hour endoscopy service, specialized nurses were available in 75 %.
      Fiberscopes were used only in 15 %. A mean of 10 +/- 12 (range: 0 - 160) bleeding
      cases/month were treated, 6 +/- 6 cases per month (60 %) were ulcer bleedings.
      Endoscopy was performed in 72 % immediately after stabilization but in all cases
      within 24 hours. The Forrest classification was used in 99 % whereas prognostic
      scores were applied only in 3 %. Forrest Ia,/Ib/IIa/IIb/IIc/III ulcers were
      indications for endoscopic therapy in 99 %/ 99 %/ 90 %/ 58 %/ 4 %/ 2 %
      respectively. Favoured initial treatment was injection (diluted epinephrine, mean
      volume 17 +/- 13 mL/lesion) followed by clipping. In re-bleedings, 93 % tried
      endoscopic treatment again. Scheduled re-endoscopy was performed in 63 %. PPI
      were used in 99.6 %, 85 % administered standard dose twice daily. PPI
      administration was changed from intravenous to oral with the end of fasting in
      nearly all hospitals. PPI administration schemes can be improved. Indications for
      Helicobacter pylori eradication followed rational principles. CONCLUSION: Medical
      and endoscopic treatment of bleeding ulcers reached a high standard, although
      some therapeutic strategies leave room for improvement. Bigger hospitals tend to
      be closer to the medical standard.

PMID- 20127601
TI  - Fulminant hepatic failure due to chemotherapy-induced hepatitis B reactivation:
      role of rituximab.
AB  - Hepatitis B virus reactivation during immunosuppressive therapies can lead to
      liver failure with very limited treatment options available. We report here on
      two cases of severe hepatitis B reactivation during chemotherapy including
      rituximab for B cell lymphoma which were treated with liver or liver-cell
      transplantation. Liver function was normal and HBV infection was unknown in both
      patients before chemotherapy was started. Impaired liver function became apparent
      after 4 and 6 courses of chemotherapy, respectively, and both patients
      experienced fulminant hepatic failure despite antiviral treatment with lamivudine
      or entecavir. Patient A underwent liver transplantation after documentation of
      complete remission of the lymphoma and survived without any evidence for
      hepatitis B recurrence. Patient B received 4 courses of hepatocyte
      transplantation but did not survive. These cases underline the importance of anti
      HBc screening in patients receiving immunosuppressive treatments in particular
      when rituximab is given. Pre-emptive antiviral treatments should be administered
      since delayed antiviral treatment is frequently unable to prevent liver failure.

PMID- 20127602
TI  - [Malignant bowel obstruction].
AB  - Malignant bowel obstruction (MBO) is a frequent complication in patients with a
      progressive malignant disorder and represents a major interdisciplinary challenge
      in palliative care. Gastroenterology plays a pivotal role in the management of
      MBO. After appropriate diagnostic work-up, it is important to define treatment
      goals with the patient and his/her relatives, which should focus on symptom
      relief. Therapeutically, surgical, endoscopic and medical options are available.
      These will be introduced based on case reports. In the international literature
      MBO is being more and more considered as a distinct entity. The aim of the
      present review is to communicate MBO as such in the German medical literature.

PMID- 20127605
TI  - [Online medical consulting service at the University Hospital Zurich before and
      after introduction of a service fee].
AB  - OBJECTIVE: The University Hospital of Zurich has been providing an anonymous
      online consultation service since 1999. In January 2008 a service fee of CHF 20.-
      was introduced. The present investigation evaluated the impact of the service fee
      on the use of the medical online consulting service. METHODOLOGY: All 8269
      requests between January 2007 and December 2008 were analysed using the following
      criteria: number, complexity and subjects (ICD-10) of the requests, personal
      statements of the users and evaluation of the online answers. RESULTS: The number
      of requests decreased by 69 % (6298 vs.1971) and the age of the users rose from
      36 +/- 16 to 40 +/- 17 years. The text length of the requests increased
      (characters: 677 +/- 463 vs. 801 +/- 539), as did the length of the answers
      (characters: 1397 +/- 3224 vs. 2391 +/- 4327). In 2008 the assistance of
      specialists at the University Hospital Zurich were called upon more frequently
      (11.1 % vs. 15.9 %). Regarding the assessments of the quality of the answers,
      there were differences in the range of positive evaluations ("good": 38 % vs. 41
      %, "excellent" 43 % vs. 36 %). DISCUSSION: The introduction of a new service fee
      resulted in a decrease in requests. At the same time, a greater number of older
      people used the service, and they asked questions that are more complex.
      Apparently, persons that probably have more medical problems have greater
      appreciation for the opportunity to ask questions and, in comparison to younger
      persons, are more willing to pay for the service. The continued positive
      evaluation given to the medical answers shows that an Internet service involving
      a fee can also be a useful supplement to the conventional physician/patient
      relationship.

PMID- 20127606
TI  - [Solitary liver tumor as a manifestation of polyarteritis nodosa].
AB  - HISTORY: A 65-year-old female was admitted with fever of unknown origin.
      DIAGNOSTIC PROCEDURES: Abdominal computed tomography showed a solid mass (7.5 cm
      in diameter) with central fluid, located in the right lobe of the liver. Fine
      needle aspiration cytology was unremarkable. Further work-up procedures for
      suspected liver abscess included colonoscopy, which surprisingly revealed
      adenocarcinoma at 13 cm from the anal orifice. THERAPY AND CLINICAL COURSE: Both
      lesions in the rectum and liver were resected. While a moderately differentiated
      (G2) adenocarcinoma of the rectosigmoid junction (stage T3/ N0) was confirmed,
      histology of the hepatic mass showed liver infarction due to polyarteritis nodosa
      of the medium-sized arteries. Treatment with 20 mg/d prednisolone was initiated
      and tapered off over the next three months. The clinical course after
      discontinuation of corticosteroids was unremarkable over a 6-month follow-up.
      CONCLUSION: It is suggested that polyarteritis nodosa of the liver occurred in
      this patient as a paraneoplastic phenomenon and subsided after resection of
      colorectal cancer and short-term immunosuppression with prednisolone.

PMID- 20127607
TI  - [Interpretation of elevated serum troponin levels in end stage renal disease -
      case 2/2010].
AB  - HISTORY AND ADMISSION FINDINGS: We report on a female patient with rheumatoid
      arthritis and end-stage renal-disease following AA-amyloidosis who presented with
      chest pain to the emergency department. INVESTIGATIONS: ECG showed no signs of
      ischemia, echocardiography revealed a concentric left ventricular hypertrophy
      with increased texture. Serum concentration of troponin I was mildly elevated
      whereas creatine kinase (CK)/ CK-MB were normal. DIAGNOSIS, TREATMENT AND COURSE:
      The chief complaints resolved spontaneously and there was no change in the serum
      troponin-I and CK/CK-MB concentrations. Coronary heart disease was ruled out by
      angiography and cardiac involvement of the underlying AA-amyloidosis was
      diagnosed. After one month, the patient suffered from a syncope complicated by a
      pelvic ring fracture with hemorrhagic shock and declined chronic dialysis
      treatment. CONCLUSION: Patients with end-stage renal disease may exhibit a
      persisting elevation of serum troponin concentration reflecting the high burden
      of cardiovascular disease. Myocardial infarction can be distinguished by the lack
      of increase in serial tests.

PMID- 20127608
TI  - [Acute abdomen in an 61-year-old patient with infantile brain damage].

PMID- 20127609
TI  - [Surgical treatment for renal cell carcinoma].
AB  - Renal cell carcinoma is chemoresistent and radio-therapy so that surgical tumour
      excision of the tumor is the only potentially curative option, either as radical
      nephrectomy or as nephron sparing surgery. As a result of continuously improving
      radiological imaging modalities, renal tumours are nowadays detected incidentally
      at an asymptomatic stage in up to 75 %. The ten-year cancer-specific survival for
      organ-confined disease (T1,T2) after R0-excision is > 90 %. Moreover, locally
      extending renal tumours (T3) can be treated successfully with five-year survival
      rates of > 65 %. In case of tumours in a single kidney or synchronous bilateral
      tumours, good functional and oncological long-term results can be achieved by
      nephron sparing surgery (imperative indication). T1 renal cell cancer (tumour
      size < 7 cm ) should be treated by nephron sparing surgery, even if the
      contralateral kidney is normal, because since this nephron-sparing approach
      ensures maximal renal reserve in the long term follow up. Minimally invasive
      techniques offer treatment also for multi-morbide patients. Which approach is to
      be selected depends on size and location of the tumour as well as on indication
      (elective or imperative), age and general health of the patient and the surgeon's
      preference.

PMID- 20127610
TI  - [Patients as customers - do we have to get used to a new parlance?].

PMID- 20127611
TI  - [Physician's duty to obtain informed consent if patients refuse indicated
      treatment].

PMID- 20127613
TI  - [68-year-old patient with exercise-induced syncope].

PMID- 20127614
TI  - [Validation of the German translation of the Eating Disorders Quality of Life
      (EDQOL)].
AB  - The aim of the study was the translation and validation of a disease-specific
      questionnaire (Eating Disorders Quality of Life, EDQOL) to measure the health
      related quality of life of eating-disordered patients. 195 patients with eating
      disorders and 109 healthy controls were examined by EDQOL and other instruments
      (SF-12, EDI, FKB-20, SEED, BSI, IIP-D and SOC-13). The EDQOL total score proved
      to have a high internal consistency. The four factorial structure of the original
      version was confirmed. There were indications of very good construct validity and
      a good sensitivity for change. For the first time, in the German-speaking part
      there is an economic, reliable and valid instrument that assesses the specific
      health-related quality of life for patients with eating disorders which is
      recommended for use in research as well as in clinical settings.

PMID- 20127615
TI  - Psychopathological rating scales as efficacy parameters in adult ADHD treatment
      investigations - benchmarking instruments for international multicentre trials.
AB  - INTRODUCTION: The selection of appropriate instruments in clinical studies is an
      essential point to detect the effects of pharmacological and/or psychotherapeutic
      treatments. METHODS: We performed a Medline search to identify the controlled
      pharmacological treatment studies and controlled and open psychotherapeutic
      investigations since 1999 in adult ADHD. The efficacy parameters were collected
      in order to compare their psychometric properties and psychopathological content.
      RESULTS: We identified 21 pharmacological and 6 psychotherapeutic treatment
      studies. The ADHD-Rating Scale-IV (ADHD-RS-IV), the Conners Adult ADHD Rating
      Scale-Observer Version (CAARS-O), and the Wender Reimherr Adult Attention
      Disorder Rating Scale (WRAADDS) are the clinical expert rating scales, which were
      used most frequently. The Conners Adult ADHD Rating Scale-Self -Report: Short
      Version (CAARS-S:S) and the Adult ADHD Self-Report Scale (ASRS) are self-report
      rating instruments which have found general acceptance. DISCUSSION: The
      instruments offer appropriate psychometric properties. The psychopathological
      item content of the ADHD-RS-IV and the CAARS-O is focused on inattention,
      impulsivity and hyperactivity. The WRAADDS comprises additionally emotional
      symptoms and disorganization.

PMID- 20127617
TI  - [Physiological monitoring and clinical assessment of patients in shock].
AB  - Shock is a life-threatening situation for which circulatory failure represents a
      major potential complication. While there are numerous disposing factors, the
      detrimental impacts on the human body are similar. Drop in blood pressure is a
      common clinical presentation. Severity of impact and chance of survival from
      shock depend heavily on the speed with which blood pressure recovers and tissue
      oxygenation is preserved. This article describes the types, pathophysiological
      process, and major complications of shock, along with relevant disposing factors,
      risk groups, assessment techniques, monitoring skills and nursing care.

PMID- 20127616
TI  - The tolerability of rTMS treatment in schizophrenia with respect to cognitive
      function.
AB  - INTRODUCTION: The purpose of this study was to assess tolerability and safety of
      high-frequency rTMS with regard to cognitive performance when conducted as "add
      on" treatment in chronic schizophrenia in-patients (n=32). METHODS: Patients, who
      were on stable antipsychotic treatment, were randomly assigned to verum or sham
      condition (double-blind). In the verum group, ten sessions of 10 Hz rTMS with a
      total of 10 000 stimuli were applied over the left dorsolateral prefrontal cortex
      (PFC) at 110% of motor threshold over a period of two weeks. The sham group
      received corresponding sham stimulation. RTMS effects on cognitive performance
      were assessed with a neuropsychological test battery consisting of the following
      tests: trail making test A and B (TMT), Wisconsin card sorting test (WCST), D2
      attention task and the "short test of general intelligence" (KAI). RESULTS: No
      statistically significant deterioration of cognitive performance was observed as
      a result of rTMS treatment. Moreover it was shown that in the verum group
      patients with a less favourable performance on the WCST at baseline tend to
      improve after rTMS treatment with regard to psychopathology as opposed to
      patients in the control group. DISCUSSION: The stability of cognitive function
      suggests good tolerability of rTMS treatment in schizophrenia. The absence of
      evidence for cognitive deterioration could be due to low and short stimulation
      parameters.

PMID- 20127618
TI  - [The current situation and trends in the clinical treatment of shock].
AB  - Shock is defined as hypoperfusion of tissues and/or organs. The initial focus of
      resuscitation following shock is on establishing an open airway and ensuring
      adequate ventilation and circulation. Causes of shock can be recognized quickly
      via clinical manifestations. A professional physical examination and observation
      of response to therapy can result in early diagnosis of the causes of unstable
      vital signs. Identification of shock symptoms in order to administer appropriate
      treatment quickly is key to saving patient lives, because "time is tissue". In
      all shock cases, treatments begin with an evaluation, resuscitation and immediate
      treatment of life-threatening symptoms. Patients may experience more than one
      kind of shock simultaneously, which further complicates their assessment and
      treatment. The critical care of shock should be done thoroughly and
      systematically in order to assess and manage patients so as to avoid dysfunctions
      in one organ damaging others. During emergency and critical management of shock
      patients, once a certain stage of assessment is completed, further evaluation is
      necessary to assess condition improvement. If improvement is confirmed,
      maintenance therapy may be considered. If improvement is not confirmed, it should
      be considered whether treatment is inadequate or misfocused, or whether the
      patient's response is atypically poor. In addition to timely resuscitation and
      ICU care, there are specific effective treatments for each type of shock. Such
      must be administered in accordance with guidelines, standard protocols and goal
      oriented approaches. Trends in shock management currently focus on integrating
      guidelines, standard protocols and goal-oriented approaches into a "treatment
      bundle", which facilitates the implementation of clinical medical care and
      completes specific goals within a specified time limit to reduce the risk of
      multiple organ failure and death due to shock.

PMID- 20127619
TI  - [Fluid resuscitation therapy application and nursing following hemorrhagic
      shock].
AB  - Hemorrhagic shock is the most important cause of early death following major
      trauma. Aggressive fluid resuscitation therapy is an important treatment approach
      for hemorrhagic shock, and nurses in critical care units must be adept at the
      skills to administer such. However, past studies have shown that failure in
      multiple organs has been induced by aggressive fluid resuscitation therapy. This
      article first discusses the two hit theory following trauma or shock, then
      discusses how aggressive crystalloid-based resuscitation strategies are
      associated with cell, multiple organs and immunological and inflammatory mediator
      dysfunction. While the Advanced Trauma Life Support (ATLS) training program has
      provided fluid resuscitation therapy guidelines since 1997, resuscitation volume,
      rate and time as well as crystalloid and colloid ratios remain uncertain.
      Therefore, we hope this article can provide evidence-based knowledge related to
      fluid resuscitation therapy in order to avoid secondary organ damage in critical
      care.

PMID- 20127620
TI  - [A study of work values, professional commitment, turnover intention and related
      factors among clinical nurses].
AB  - BACKGROUND: The high rate of turnover in nursing positions is a global problem.
      There have been few studies done addressing the relationship between work values
      and nurse turnover intention. PURPOSE: The purpose of this study was to explore
      the relationship between work values, professional commitment and turnover
      intention among clinical nurses. METHOD: A cross-sectional survey was conducted
      between February 1st to March 10th, 2008 on a convenience sample of nurses, all
      of whom had at least a half year of work experience at one of four teaching
      hospitals in Taiwan. RESULTS: A total of 289 valid responses were received, with
      a response rate of 96.3%. Major findings included: (1) Nurses who were older, had
      more years of school, had worked more years, held specific job duties, earned a
      higher salary, held Buddhist beliefs, or were married with two or more children
      presented higher work values and professional commitment and lower turnover
      intention; (2) As a group, total work values and professional commitment scores
      corresponded negatively with turnover intention scores; (3) Significant factors
      affecting turnover intent in clinical nurses included professional commitment,
      institution characteristics, Buddhist beliefs and salary. These four variables
      accounted for 52.2% of the variation in turnover intention. CONCLUSIONS /
      IMPLICATIONS FOR PRACTICE: This study indicated that nurses with higher work
      values and professional commitment tend to exhibit less turnover intention. It is
      highly recommended to develop strategies to bolster the teaching of altruistic
      values and professional commitment in nursing education in order to reduce
      turnover intent. Also, further studies on the influence of religious beliefs and
      organizational attributes on nurse turnover intentions are also suggested.

PMID- 20127621
TI  - [Implementation and evaluation of a proper dietary behavior program in diabetes
      support groups].
AB  - BACKGROUND: Active promotion in recent years of the Diabetes Share Care Program
      by the national Department of Health and the medical profession has gradually
      established a diabetes support system as well as patient support groups in
      Taiwan. The program concept holds that, by participating in a patient support
      group, diabetes patients and people in high risk categories will learn to adopt a
      healthier lifestyle in order to delay / avoid diabetes onset and complications.
      PURPOSE: Within the diabetes support group framework, we implemented correct
      dietary behavior programs and evaluated their efficacy. METHOD: A study using a
      quasi-experimental, single-group pretest and posttest design was carried out from
      December 2007 to May 2008. Participants included 48 registered patient members of
      a diabetes patient group located at a regional teaching hospital in Kaohsiung.
      Researchers used the Donabedian framework to evaluate program efficacy. RESULTS:
      Results indicated that the program could effectively promote proper dietary
      behavior in patients. CONCLUSION: Providing instant data during program execution
      and evaluation can enhance program efficacy. We hope that this experience can
      serve as a reference for medical staff when executing such programs.

PMID- 20127622
TI  - [Racing with illness: the life experiences of mothers of children with duchenne
      muscular dystrophy].
AB  - BACKGROUND: Understanding the life experiences of mothers of children with
      Duchenne Muscular Dystrophy (DMD) is very important for nurses focused on
      providing family care. The present study provides valuable insight into this
      issue, as few studies on this important topic have been done previously. PURPOSE:
      The objective of this study was to explore thoroughly the life experiences of
      mothers taking care of DMD children from their own perspectives. METHODS: This
      study used a phenomenological approach. A purposive sample of 11 mothers of DMD
      children was recruited from the Taiwan Muscular Dystrophy Association (Southern
      Chapter). All agreed to join this study and were able to speak either Taiwanese
      or Mandarin fluently. Data collected through one-to-one, in-depth interviews were
      analyzed using the Colaizzi (1978) phenomenological methodology. RESULTS: Results
      showed that the life experiences of mothers of DMD children were typified by the
      theme, "racing with illness". Four categories emerged from interview data,
      including: "loss of time and space", "physical and psychological pain", "damage
      to relationships", and "financial difficulties". CONCLUSIONS: Study findings may
      help us better understand the life experiences of mothers of children with DMD
      and may serve as an important reference with regard to how best to coordinate
      government, medical, education and other support organizations to provide such
      mothers with greater support and assistance and DMD children with better care.

PMID- 20127623
TI  - [The exploration of the lived experiences of schizophrenic patients and family
      members facing the fear of illness hereditary].
AB  - BACKGROUND: Schizophrenia negatively affects both patients and their families.
      What are the effects of this incurable, potentially hereditary disease on daily
      life? Related research shows that schizophrenics tend to experience 'uncertainty'
      in daily life. Discussions on 'uncertainty' experienced in daily life in the
      context of concerns regarding hereditary illness remain scarce in Taiwan.
      PURPOSE: This research was designed to gather important data on schizophrenic
      patients and their family members related to their uncertainties about disease
      heredity. METHODS: Participants were recruited from the psychiatric unit and
      outpatient services department at two hospitals in Hsinchu County. Research
      subjects included a total of six schizophrenics and six family members. RESULTS:
      The three topics deduced from data analysis included: 1. marriage / family
      difficulties rooted in feelings of suffering and torture related to the psychosis
      and uncertainties regarding disease heredity; 2. evolution from doubt to trust as
      patients gradual accept choices and make decisions related to disease heredity;
      and 3. dealing with disease heredity again after having made a successful
      transition (i.e. persistence to maintain family ties). CONCLUSIONS / IMPLICATIONS
      FOR PRACTICE: Both patients and family members experienced worry and fear due to
      uncertainty about the hereditary condition of the disease. Some experienced
      emotional responses such as anxiety and helplessness. Research results are
      expected to help nursing personnel understand the multiple effects and impacts of
      uncertainty toward illness heredity experienced by the patients and their
      families in order to provide better consultation and medical care quality under
      differing circumstances depending on the individual characteristics of patients
      and their families.

PMID- 20127624
TI  - [Nursing knowledge: the evolution of scientific philosophies and paradigm
      trends].
AB  - Different aspects of philosophy are derived from different paradigms that contain
      various main points, some of which are repeated or overlap. Belief and practice
      are two components of a paradigm that provide perspective and framework and lead
      to nursing research. Changes in healthcare have popularized empirical and
      evidence-based research in the field of nursing research. However, the evidence
      base study approach has given rise to a certain level of debate. Until now, no
      standard paradigm has been established for the nursing field, as different
      professionals use different paradigms in their studies. Such provides certain
      limitations as well as advantages. The quantitative aspects of a nursing paradigm
      were developed by Peplau and Henderson (1950) and Orem (1980). Such remained the
      standard until 1990, when Guba and Parse proposed qualitative viewpoints in
      contextual features. Therefore, the nursing paradigm has made great contributions
      to the development of knowledge in nursing care, although debate continues due to
      incomplete knowledge attributable to the presentation of knowledge and insight
      within individually developed paradigms. It is better to apply multiple paradigms
      to different research questions. It is suggested that better communication
      amongst experts regarding their individual points of view would help nursing
      members to integrate findings within the global pool of knowledge and allow
      replication over multiple studies.

PMID- 20127625
TI  - [Exploring the issue of cervical cancer prevention and control in women living
      with HIV/AIDS].
AB  - Shared risk factors mean that women engaging in unprotected sex are at risk of
      contracting both the human immunodeficiency virus (HIV) and the human
      papillomavirus (HPV). As HIV suppresses bodily immune systems, an HIV-positive
      woman with HPV will likely see a faster progression of cancer cells around the
      cervix. Therefore, it is important to prevent and control cervical cancer in HIV
      positive women. Findings from the literature on this topic include: 1) HIV
      positive women face a relatively greater risk of: HPV surveillance, contracting
      high-risk HPV subtypes, contracting more subtypes of HPV, longer HPV clearance
      time, and acquisition, persistence, progression and relapse of cervical dysplasia
      and cancer and 2) Factors related to cervical cancer progression in HIV-positive
      women correlated with lower CD4 counts and higher viral loads, but not with anti
      HIV medication. Based on such, we suggest: 1) Medical and social service systems
      should target appropriate safe sex education and sex counseling to HIV-positive
      women; 2) HIV-positive women should receive a free Pap smear twice yearly; 3)
      Health authorities should monitor Pap smear screening rates and HIV-positive
      results; 4) Encourage women with STDs and cervical dysplasia to undergo HIV and
      HPV testing during pretest counseling and regularly follow Pap smear results; and
      5) Enhance HPV prevention in men.

PMID- 20127626
TI  - [The affect of gender on caregiving: a study of male nurses].
AB  - Caring, the essence of nursing, is widely viewed as a feminine activity.
      Therefore, determining the existence and extent of differences in caring shown by
      male nurses in comparison with their female counterparts is a matter that
      requires further discussion. This article discusses the effects of gender
      differences on nursing care provided by male nurses according to analyzing the
      essential elements of caring. Findings indicate that certain caring behaviors
      performed by male nurses differ from their female colleagues due to extant
      internal conflicts between masculine and caring concepts. This article proposes
      two suggestions to nursing educators: 1. When training male nurses, in addition
      to emphasizing the value of caring, instructors should also emphasize teaching
      caring competence; 2. Based on an acceptance of diversity, instructors should
      accept the existence of differences between male and female nurse caring
      behaviors due to fundamental gender differences.

PMID- 20127627
TI  - [A review of current studies on leisure activities performed by community
      dwelling elders].
AB  - This article reviewed and summarized the findings of previously published studies
      on the leisure activities of community elders over 55 years of age. A total of 17
      related articles, published before 2008, were identified in the search of
      electronic databases, which included the Chinese Periodical Table of Contents
      Index Image System, CEPS, Medline and Ageline. Leisure activities measurements
      used in this study consisted of recoding activities either categorically or by
      frequency. The majority of research indicated that elderly engage in primarily
      static activities and that participation in leisure activities had positive
      effects on cognitive and psychological health. However, inconsistencies in
      results were found due to differences in measurement tools and sample populations
      used among studies, making it difficult to conduct a valid comparison of specific
      features of elderly leisure activities. Most current leisure activity studies
      utilize cross-sectional research methodologies with restricted topics, which
      result in limited applicability of research results. In conclusion, we suggest
      that future studies should develop instruments to assess leisure activities that
      correspond to local conditions identified through qualitative research. With
      such, researchers can study different age groups by applying relevant ageing
      theories to construct empirical data related to current elderly leisure
      activities.

PMID- 20127628
TI  - [Risk assessment: a concept analysis].
AB  - Risk assessments are conducted to assess the negative influences and potential
      losses related to a prospective goal or decision. The main practical purpose of
      risk assessment is to provide information, which can then be used to manage
      identified potential risks to avoid their occurrence or minimize their influence.
      To date, the risk assessments have primarily been applied to finance,
      environmental pollution and employment. Risk assessment has been applied only in
      a limited manner in the fields of medical treatment and nursing. Literature on
      risk assessment lack analysis that is systematic and complete. This article
      applies the methodology of Walker and Avant (2005) to analyze the concept of risk
      assessment. Steps include a review of the literature on conceptual definitions of
      risk assessment, determining the defining attributes of risk assessment, model
      construction, defining parameters and related cases, and identifying antecedents
      and consequences. Once completed, empirical references of risk assessment were
      explored. The authors hope that this analysis can assist nursing stuff to gain a
      better understanding of risk assessment concepts in order to apply knowledge
      gained to clinical practice. As such, nursing stuff will be able to apply the
      concept of risk assessment to identify risk, control risk, and reduce the
      occurrence and loss of accidents.

PMID- 20127629
TI  - [Promoting nursing competitiveness: introduction to the digital divide].
AB  - Increasingly sophisticated information technology (IT) has widened the gap (the
      so-called "digital divide") between those with effective access to IT resources
      and those without. Problems related to the digital divide exist in every country.
      In addition to level of familiarity with technology, the divide can also be
      influenced by factors of race, gender, age, education, economic status and area
      of residence. The digital divide may be ameliorated through technology
      innovations in terms of access to information, information application and
      information literacy. As IT is an increasingly significant component of modern
      healthcare, it may be expected that the "width" of the potential gap widens as IT
      applications increase in sophistication. Nursing professionals must keep abreast
      of advancing technologies in order to narrow the digital divide. To cope with
      this challenge, nursing professionals should enhance their understanding of new
      technologies beyond what is taught in formal education curricula. This knowledge
      enhancement may be attained through self learning or on-the-job training in
      nursing informatics. Content could cover hospital information system (IS) usage,
      security, applications and web access. This will improve the ability of nursing
      staff to face the current IT challenge.

PMID- 20127630
TI  - [Concept analysis of dysphagia].
AB  - Swallowing is a complex process. Dysphasia may interrupt normal life activities
      such as having meals with family and friends and enjoying food. Consequently,
      patients with dysphasia are less likely to attend social activities, which may
      lead to social isolation and frustration. A review of the literature in Taiwan
      revealed a lack of recent systematic analysis on dysphasia. The purpose of this
      article was to discuss dysphasia within the concept analysis framework provided
      by Walker and Avant (2004). This article verified and confirmed the conceptual
      characteristics of dysphasia; identified antecedents and consequences; and
      elaborated on previous cases (including model, borderline, contradictory, and
      related cases). Empirical referents of dysphasia were also explored. It is hoped
      that this paper may provide a better understanding of the concept of dysphasia,
      which nurses may apply to clinical practice.

PMID- 20127631
TI  - [Immigrant women & postpartum depression].
AB  - The immigrant population in Taiwan has increased significantly over the past
      decade, and immigrants now comprise a significant proportion of the women in
      Taiwan receiving maternal care. Postpartum stress and depression are important
      physical and mental health issues. This article used a systemic review of
      published articles to understand the general incidence of postpartum depression
      amongst immigrant women. Articles reviewed included those published in MEDLINE,
      PubMed, Proquest and CEPS in either English or Chinese. A systematic literature
      review of 20 identified original research papers was conducted to explore
      postpartum depression in immigrant women. One article addressed the experience of
      healthcare providers responsible to care for immigrant women suffering from
      postpartum depression. Other articles discussed factors of influence on
      postpartum depression in immigrant women or related experiences. Results show
      that immigrant women have a higher incidence of postpartum depression than the
      overall population. This incidence is even higher amongst immigrant women from
      minority groups. In addition to socioeconomic influence factors, social support
      and acculturation abilities were also found to be significant predictive factors
      of postpartum depression in immigrant women in Taiwan.

PMID- 20127632
TI  - [Comment on diagnosis and treatment of iron deficiency without anemia].

PMID- 20127633
TI  - [Prostate cancer].

PMID- 20127634
TI  - [CME ECG 28].

PMID- 20127635
TI  - [What is your diagnosis? Essential tremor].

PMID- 20127636
TI  - [Carpal tunnel syndrome--modern diagnostic and management].
AB  - The carpal tunnel syndrome is the most common entrapment neuropathy (about 3% of
      the adults are affected). It is characterized by pain and paresthesia along the
      distribution of the median nerve. Thenar muscle atrophy with corresponding muscle
      weakness is a late manifestation of advanced disease. Electrophysiological tests
      are helpful in suggesting the diagnosis. An imaging with a magnetic resonance
      tomography may be used in the diagnosis of atypical cases. Ergonomic manoeuvres,
      oral steroids and steroidal injections may alleviate symptoms in mild cases.
      Surgical decompression of the carpal tunnel is the classical treatment of severe
      cases as well as for those who do not respond to conservative treatment. After
      surgery patients usually show excellent results. The following article discusses
      clinical aspects, diagnosis and current therapeutic options.

PMID- 20127637
TI  - [Wilson's Disease].
AB  - Wilson's disease is a rare inherited disorder of copper metabolism. If left
      untreated, the disorder has a fatal course within a few years after symptom
      onset. If discovered early, effective treatment is available, preventing further
      clinical deterioration and leading to a normal life expectancy. Accumulation of
      copper in liver and brain can lead to a variety of unspecific hepatic, neurologic
      and psychiatric symptoms such as jaundice, tremor, ataxia or depression. In
      patients under the age of 40 with unexplained hepatic, neurologic or psychiatric
      symptoms, Wilson's disease must be considered. Diagnosis can be made by
      measurement of urinary copper excretion and other tests as required. Lifelong
      decoppering treatment must be maintained. For the detection of deterioration of
      the disease or adverse effects of the medication as well as for the assessment of
      therapeutic compliance, regular clinical controls are necessary.

PMID- 20127638
TI  - [In depth analysis of 2 studies of prostate cancer screening--what makes sense?].

PMID- 20127639
TI  - [Non-alcoholic fatty liver].

PMID- 20127640
TI  - [Ascites and hematuria after falling in an alcoholic patient].
AB  - Isolated ruptures of the urinary bladder following minor traumas are a rare
      abdominal lesion. Diagnosis and treatment are a challenge to emergency physicians
      and surgeons. This case shows a 46-year-old patient admitted for a minor brain
      injury after falling during an episode of alcoholic intoxication. Ultrasound and
      CT scan of the abdomen showed intraabdominal fluid without a parenchymatous
      lesion. Also a hematuria was significant. The retrograde cystography showed
      intraabdominal contrast agent. The rupture of the urinary bladder was confirmed
      by laparoscopy and was intracorporal sutured in double layer technique. Without
      any postoperative complications the patient was discharged after 4 days. The
      retrograde cystography after 10 days showed no leckage and the urinary catheter
      could be removed.

PMID- 20127641
TI  - [Regular PSA screening does not reduce prostate cancer mortality].

PMID- 20127642
TI  - [PSA screening of 55 to 69 year old men reduces prostate cancer mortality].

PMID- 20127644
TI  - [CME--ultrasound diagnosis. Dysuria in a young woman].

PMID- 20127645
TI  - [Medical art column. Body experiment in art].

PMID- 20127646
TI  - [Medical sculpture puzzle. Abel Dimier].

PMID- 20127647
TI  - [Infectious canine hepatitis in 4 dogs in Switzerland].
AB  - Infectious canine hepatitis in 4 Dogs in Switzerland. Four dogs presented with
      nonspecific symptoms of lethargy, vomiting, diarrhea, fever and weakness.
      Laboratory results were consistent with hepatopathy and disseminated
      intravascular coagulation. Three dogs died, one survived. In the three deceased
      dogs, a diagnosis of infectious canine hepatitis (ICH) was made based on
      histological findings and positive immunhistochemistry results for canine
      adenovirus-1 (CAV-1). In the surviving dog, an antemortem diagnosis of ICH was
      determined via positive polymerase chain reaction results from blood, occular,
      nasal and preputial discharge as well as from urine. Since the introduction of
      widespread vaccination, the incidence of CAV-1 infection in dogs is low. However,
      the disease has not been eradicated and should be considered when clinical signs
      consistent with ICH are present.

PMID- 20127648
TI  - [Analysis of dogs and cats behavior during the physical examination in veterinary
      practice].
AB  - The behavior of 100 healthy dogs and 100 healthy cats was analysed during their
      physical examination from "head to tail". A complete physical examination was
      possible without restraint in 70 % of the dogs and 76 % of the cats. Only a
      partial examination was possible in 24 % of the dogs and 20 % of the cats. The
      physical examination could not be correctly performed in 6 % of the dogs and 4 %
      of the cats. 16 % of the dogs and 13 % of the cats showed aggressive or dangerous
      behavior. Male dogs were more frequently aggressive than bitches (p = 0.01).

PMID- 20127649
TI  - [Rudolf Trachsel (1804 - 1894): animal doctor and philanthropist].
AB  - The animal doctor Rudolf Trachsel (1804 - 1894) from Rueggisberg was an
      outstanding representative of his guild. Not only a successful practitioner and
      mentor of the veterinary school in Berne, he was also politically involved on a
      communal and cantonal level. In addition to this, he was an eminent
      philanthropist, who brought light into the "poorhouse of the canton of Berne". He
      actively and successfully fought against poverty and misery by teaching people to
      save, and for this purpose he founded in Rueggisberg the region's first bank 175
      years ago.

PMID- 20127650
TI  - Echocardiographic findings in a goat with cor pulmonale secondary to chronic
      parasitic pneumonia.
AB  - A four-year old goat was presented for anorexia and apathy since kidding one week
      earlier. Physical examination revealed dyspnea, extensive ascites and bilateral
      distended jugular veins, suggestive of congestive right heart failure. The
      echocardiographic findings of severe right ventricular and atrial dilatation were
      consistent with right heart failure. In the absence of abnormalities in the right
      ventricular outflow tract a diagnosis of cor pulmonale secondary to lung disease
      was posed. Due to a poor prognosis, the goat was euthanized. Necropsy confirmed
      cor pulmonale and identified severe chronic parasitic pneumonia as underlying
      cause. Echocardiography is an interesting tool also applicable in the farm for
      diagnosing heart diseases in goats, and its use should help to avoid unnecessary
      therapy in cases with a poor prognosis.

PMID- 20127652
TI  - [Reconversion of active principles in veterinary medicine and specific
      regulations for food producing animals].

PMID- 20127653
TI  - [Limitations in the choice of a department staff].

PMID- 20127655
TI  - Outcomes of renal transplants from spousal donors: 25 years of experience at our
      center.
AB  - OBJECTIVES: Many transplantation teams have attempted renal transplants from
      living unrelated kidney donors, as well as from cadaveric and living related
      kidney donors. In this study, we evaluated the results for renal transplants from
      spousal donors at our center. METHODS: We retrospectively analyzed renal
      transplant patients from spousal donors from 1983 to 2008. A total of 25 patients
      who underwent a cadaveric donor renal transplant from 1983 to 2008 were also
      studied as a control group. Patients were evaluated regarding patient and graft
      survival at 1 and 5 years of follow-up. Acute rejection, delayed graft function,
      infections, and late complications were recorded. RESULTS: Thirty-eight male,
      spousal transplant recipients (group 1), 21 female, spousal transplant recipients
      (group 2), and 25 cadaveric donor transplant recipients were included this study.
      Graft survival rates were 96% in group 1 and 100% in group 2 (p=0.76) at 1-year
      follow-up. Patient survival rates in group 1 and 2 were both 100% at 1-year
      follow-up. Graft survival rates were 80% in group 1 and 100% in group 2 (p=0.12)
      at 5-year follow-up. Patient survival rates were 90% in group 1 and 100% in group
      2 (p=0.56) at 5-year follow-up. Acute rejection rates were 10% (group 1) and 33%
      (group 2) (p=0.03); delayed graft function rates were 0% (group 1) and 10% (group
      2) (p=0.05); infection rates were 16% (group 1) and 5% (group 2) (p=0.21) as
      early period posttransplant complications. CONCLUSION: Results for transplants
      between spouses in our groups were comparable to those previously reported in the
      literature. Acute rejection rates were mildly higher in female recipients than in
      the male recipients due to pre-sensitization arising from previous pregnancies;
      however long-term patient and graft survival rates were not significantly
      different between female and male recipients.

PMID- 20127656
TI  - Breakdown of the gut barrier in patients with multiple organ dysfunction syndrome
      is attenuated by continuous blood purification: effects on tight junction
      structural proteins.
AB  - BACKGROUND: Breakdown of the gut barrier increases intestinal permeability and
      allows movement of intraluminal contents across the mucosa, which can lead to
      distant organ injury and multiple organ dysfunction syndrome (MODS). Intestinal
      permeability is associated with alterations in cellular tight junctions involving
      the structural proteins occludin and zonula occludens-1 (ZO-1). The aim of this
      study was to investigate the effect of continuous blood purification (CBP) on gut
      barrier function in patients with MODS. METHOD: Serum diamine oxidase (DAO) and
      endotoxin, epithelial monolayer permeability, and transepithelial electrical
      resistance (TER) were used as markers for the assessment of gut barrier function
      in 22 patients with MODS who underwent continuous venovenous hemofiltration (CWH)
      for 24 hours. Blood samples were taken from patients at 0, 6, 12, and 24 hours
      during CWH therapy. Serum DAO and endotoxin were determined by
      spectrophotography. Permeability and TER were assessed using Caco-2 cell
      monolayers. Occludin and ZO-1 protein levels were analyzed by immunoblotting and
      immunofluorescence staining. And inducible nitric oxide synthase (iNOS) mRNA
      levels and nitric oxide (NO) production were determined by real-time PCR and
      spectrophotography, respectively. RESULT: Gut barrier dysfunction was evident in
      patients with MODS compared with normal controls. Serum DAO, endotoxin levels,
      and epithelial permeability were elevated, while TER was decreased in patients
      with MODS, and this change was more pronounced in nonsurvivors. Breakdown and
      reorganization of occludin and ZO-1 away from tight junctions was found in all
      MODS patients. After CBP treatment, APACHE II and MODS scores improved
      significantly. Serum DAO and endotoxin levels and epithelial permeability also
      diminished, while TER increased in all patients; CBP significantly attenuated
      breakdown and reorganization of tight junction proteins, and also attenuated the
      inflammation-induced increase in iNOS mRNA expression and NO production.
      CONCLUSION: Breakdown of gut barrier function is present in patients with MODS
      and may be correlated with poor outcomes in the disease. CBP can not only improve
      the general conditions, as measured by the APACHE II score, but also improve gut
      barrier dysfunction by attenuating the breakdown and reorganization of occludin
      and ZO-1. This beneficial effect of CBP on gut barrier dysfunction is associated
      with down-regulation of iNOS.

PMID- 20127657
TI  - Predicting outcomes in critically ill patients with acute kidney injury
      undergoing intermittent hemodialysis--a retrospective cohort analysis.
AB  - PURPOSE: Despite advances in the management of critically ill patients with acute
      kidney injury (AKI), the prognosis is poor. The evidence base on risk factors for
      poor outcomes in these patients is scarce. Our aim was to identify predictors of
      outcome in AKI patients undergoing intermittent hemodialysis (IHD). METHODS: We
      retrospectively analyzed patient records from consecutive, critically ill
      patients with AKI treated with IHD in one teaching secondary care hospital from
      2002 to 2006. We used multivariate Cox proportional hazard regression analysis to
      identify predictors of mortality, hemodynamical instability during hemodialysis
      and failing renal recovery. RESULTS: Totally, we included 39 patients with a mean
      APACHE II score of 20.1 (SD 7.5) who had an average of 5.1 +/- 4.8 hemodialysis
      sessions. All-cause mortality was 35.9% (14/39 patients). In multivariate
      analysis, pre-existing cardiac co-morbidity (HR 1.92 [0.58-6.47]), metabolic
      acidosis (2.40 [0-74-7.74]) and presence of ARDS (1.83 [0.52-6.46]) were the
      strongest predictors. 7 patients (18%) sustained new hemodynamic instability
      during hemodialysis, for which ARDS (6.42 [0.64-64.03]) was a strong predictor.
      Among survivors, 20 patients (80%) had partial or complete renal recovery.
      Preexisting renal insufficiency (3.13 [0.34-29.13]) and high net ultrafiltration
      quantities (3.30 [0.40-26.90]) were the strongest predictors for failing renal
      recovery. As a consequence of the small samples size none of the associations was
      statistically significant. CONCLUSIONS: Presence of ARDS and high net
      ultrafiltration rates seem to represent key factors affecting prognosis in
      patients with AKI undergoing IHD. Targeting these risk factors may improve the
      poor prognosis of these patients.

PMID- 20127658
TI  - A safer method for studying hormone metabolism in an Asian elephant (Elephas
      maximus): accelerator mass spectrometry.
AB  - Noninvasive hormone assays provide a way to determine an animal's health or
      reproductive status without the need for physical or chemical restraint, both of
      which create unnecessary stress for the animal, and can potentially alter the
      hormones being measured. Because hormone metabolism is highly species-specific,
      each assay must be validated for use in the species of interest. Validation of
      noninvasive steroid hormone assays has traditionally required the administration
      of relatively high doses of radiolabelled compounds (100 uCi or more of (14)C
      labeled hormone) to permit subsequent detection of the excreted metabolites in
      the urine and feces. Accelerator mass spectrometry (AMS) is sensitive to
      extremely low levels of rare isotopes such as (14)C, and provides a way to
      validate hormone assays using much lower levels of radioactivity than those
      traditionally employed. A captive Asian bull elephant was given 1 uCi of (14)C
      testosterone intravenously, and an opportunistic urine sample was collected 2 hr
      after the injection. The sample was separated by HPLC and the (14)C in the
      fractions was detected by AMS to characterize the metabolites present in the
      urine. A previously established HPLC protocol was used, which permitted the
      identification of fractions into which testosterone sulfate, testosterone
      glucuronide, and the parent compound testosterone elute. Results from this study
      indicate that the majority of testosterone excreted in the urine of the Asian
      bull elephant is in the form of testosterone sulfate. A small amount of
      testosterone glucuronide is also excreted, but there is no parent compound
      present in the urine at all. These results underscore the need for enzymatic
      hydrolysis to prepare urine samples for hormone assay measurement. Furthermore,
      they highlight the importance of proper hormone assay validation in order to
      ensure accurate measurement of the desired hormone. Although this study
      demonstrated the utility of AMS for safer validation of noninvasive hormone
      assays in nondomestic species, this methodology could also be applied to studies
      of nutrient metabolism and drug pharmakokinetics, both areas in great need of
      further study in wildlife species.

PMID- 20127659
TI  - How many founders, how large a population?
AB  - The number of population founders and the size of the population are two
      important variables in determining how much gene diversity can be retained in a
      population. A model is developed to determine the most cost-effective balance of
      those two variables, based on comparing the marginal costs of increasing the
      number of founders vs. increasing the population size. Marginal costs, in this
      case, are the costs of increasing the number of founders or the population size
      by one animal. For a goal of retaining 90% gene diversity for 10-15 generations
      (approximately 100 years), the current recommendation of 20 effective founders is
      very close to the least-cost solution when the ratio of the marginal costs is
      equal to one. However, when the ratio is greater or less than one that number can
      change considerably.

PMID- 20127660
TI  - Cyclic AMP signaling in bivalve molluscs: an overview.
AB  - The cyclic AMP (cAMP)-dependent signaling accounts for the control of cellular
      cascades involved in many physiological functions, and a wealth of information is
      available on the cAMP system that operates in mammalian cells. Nevertheless, cAMP
      has a central role also in nonmammalian vertebrates and invertebrates. The
      present review aims at examining the information available on bivalve molluscs,
      from the first studies carried out in the early 1980s to the last progresses made
      in the present days. The major focus is on the structural and operational
      characteristics of the main actors of the signaling pathway, i.e., adenylyl
      cyclase, G proteins, and protein kinase A, and on the role played by the cyclic
      nucleotide on smooth muscle, heart, gills, gonads, and metabolism regulation.
      Moreover, recent evidence regarding the cAMP system as a target of environmental
      stress factors are discussed. It will become clear that cAMP does play a wide and
      important role in bivalve physiology. Several issues have been sufficiently
      clarified, although investigated only in a few model species. However, further
      fundamental aspects remain unknown, mainly regarding molecular features and
      interactions with other signaling pathways, thus requiring further elucidation.

PMID- 20127661
TI  - Seasonal variations in the biochemical composition and reproductive cycle of the
      ghost crab Ocypode quadrata (Fabricius, 1787) in Southern Brazil.
AB  - The ghost crab, Ocypode quadrata, is found on sandy beaches from the United
      States to Southern Brazil. Because there is still little information about the
      metabolism and reproduction of O. quadrata on the southern coast of Brazil, the
      objectives of this study were to (i) evaluate the effect of seasonal variations
      on the carbohydrate, lipid, and protein metabolism of O. quadrata at Rondinha
      Beach, a beach with high anthropogenic activity, and to compare it with data from
      Siriu Beach, which has less human activity; and (ii) describe the effect of
      seasonal variations on the histological characteristics of male and female
      gonads, in order to assess the reproductive capacity of the crabs. The gonads of
      male crabs showed no significant variations in the gonadosomatic index (GSI) and
      glycogen levels; however, histological analysis of the testes revealed that they
      are mature in the summer. In females, the GSI and glycogen values are higher in
      summer, concomitantly with the presence of mature oocytes. These results suggest
      that the reproductive peak of O. quadrata occurs in summer. The seasonal analysis
      of the biochemical parameters, as well as comparison with Siriu Beach,
      demonstrated that the ghost crabs of Rondinha Beach have a different pattern of
      metabolism than those of Siriu. This difference may be a consequence of
      differences in the environmental conditions as well as in the anthropogenic
      pressures, such as vehicle traffic and the increase in human population at the
      beach in summer.

PMID- 20127662
TI  - Amelioration of oxidative stress in red blood cells from patients with beta
      thalassemia major and intermedia and E-beta-thalassemia following administration
      of a fermented papaya preparation.
AB  - In beta-hemoglobinopathies, such as beta-thalassemia (thal) and sickle cell
      anemia, the primary defects are mutations in the beta-globin gene. However, many
      aspects of the pathophysiology are mediated by oxidative stress. Fermented papaya
      preparation (FPP), a natural health food product obtained by biofermentation of
      carica papaya, has been shown to limit oxidative stress both in vitro and in
      vivo. We studied the effect of FPP on two groups of beta-thal patients: beta
      thal, major and intermedia, (in Israel) and E-beta-thal (in Singapore). The
      results indicated that in both groups FPP treatment increased the content of
      reduced glutathione (GSH) in red blood cells (RBC), and decreased their reactive
      oxygen species (ROS) generation, membrane lipid peroxidation, and externalization
      of phosphatidylserine (PS), indicating amelioration of their oxidative status,
      without a significant change in the hematological parameters. Since the turnover
      of the erythron is relatively slow, it is possible that longer duration of
      treatment, probably with the addition of an iron chelator, is required in order
      to achieve the latter goals.

PMID- 20127663
TI  - The tocotrienol-rich fraction from rice bran enhances cisplatin-induced
      cytotoxicity in human mesothelioma H28 cells.
AB  - Resistance to chemotherapy (chemoresistance) is a serious problem in malignant
      mesothelioma, a highly aggressive neoplasm. Gamma-tocotrienol (gamma-T3) can
      sensitize various cancerous cells to chemotherapeutic agents by inhibiting
      pathways that lead to treatment resistance. In this study, we investigated the
      modulating effect of tocotrienol-rich fraction (TRF) from rice bran, which is
      abundant in gamma-T3, on chemoresistance in human MM H28 cells. TRF treatment
      caused a marked reduction in the viability of H28 cells in a dose-dependent
      manner, while cisplatin treatment had no effect on the cells, indicating that H28
      cells are resistant to cisplatin. A significant increase in cytotoxicity was
      observed in H28 cells treated with TRF, and this effect was enhanced by the
      combination treatment with cisplatin. The cytotoxic effect was closely related to
      the inhibition of phosphatidylinositol 3-kinase (PI3K)-AKT signaling.
      Inactivation of Akt signaling by TRF or the combination with cisplatin mitigated
      cisplatin-induced activation of Akt, resulting in reducing the chemoresistance
      H28 cells to cisplatin. Reduced cell viability and attenuated chemoresistance of
      the H28 cells against cisplatin were also observed following the use of a PI3K
      inhibitor, LY294002. These results suggest that the combination therapy of
      cisplatin with TRF is a plausible strategy for achieving tolerance for the
      chemotherapeutic agent in MM therapy.

PMID- 20127664
TI  - Behavioural characterization of four endemic Stachys taxa.
AB  - We performed a basic behavioral characterization of methanol extracts of four
      Balkan endemic Stachys taxa: S. anisochila (SA), S. beckeana (SB), S. plumosa
      (SP) and S. alpina subsp. dinarica (SAD). The behavioral activity of extracts
      dosed intraperitoneally in the range 100-400 mg/kg was examined in adult male
      Wistar rats, in the elevated plus maze, spontaneous locomotor activity, and grip
      strength tests, mainly predictive of anxiolytic, sedative and myorelaxant
      actions, respectively. All investigated Stachys extracts lacked anxiolytic or
      myorelaxant activities, while SB at 400 mg/kg exerted an anxiogenic-like effect.
      The study with the selective antagonist beta-CCt showed that the sedative effect
      of SAD was only partially mediated by GABAA receptors containing the alpha1
      subunit. While discernible, the behavioral effects of SA and SP were not
      distinct. In all extracts, chlorogenic acid and verbascoside were identified. In
      SA, SB, and SAD the flavonoid fraction was constituted of isoscutellarein and
      hypolaetine glycosides, while in SP chrysoeriol and apigenin glycosides were
      present. The results reveal the psychotropic potential of four endemic Stachys
      taxa, of which SAD appeared most promising as a natural sedative.

PMID- 20127665
TI  - Antiplasmodial and cytotoxic activity of phloroglucinol derivatives from
      Hypericum erectum Thunb.
AB  - The chloroform extracts of whole plants of Hypericum erectum were investigated
      for antiplasmodial activity against chloroquine-sensitive strains of Plasmodium
      falciparum. Five phloroglucinol derivatives, otogirin (1), otogirone (2),
      erectquione A (3), erectquione B (4), and erectquione C (5) were isolated from
      the whole plants of H. erectum. Also, five compounds were evaluated for in vitro
      antiplasmodial activities as well as their cytotoxic potential on SK-OV-3 cancer
      cell line cells. Compounds 2, 4 showed notable growth inhibitory activity against
      chloroquine-sensitive strains of Plasmodium falciparum with IC(50) values from
      5.6 and 7.2 microM. This compound showed no significant cytotoxicity (IC(50) >
      150 microM) evaluated using SK-OV-3 cancer cell line cells.

PMID- 20127666
TI  - Measures of arch height and their relationship to pain and dysfunction in people
      with lower limb impairments.
AB  - BACKGROUND AND PURPOSE: Debate surrounds the theory that foot structure, and more
      specifically, the attitude of the midfoot as typified by the longitudinal arch,
      is associated with complaints of pain and injuries of the lower extremity.
      Recently, two simple clinical measures of arch height, the arch ratio (AR) and
      the longitudinal arch angle (LAA), have been reported as valid and reliable in
      the literature. The LAA has been found to approximate the lowest point of the
      arch during walking and running while the main strengths of the AR are that the
      measure takes into account foot size and arch mobility. We modified the AR so
      that the modified AR (mAR) would be measured in a similar fashion as the LAA to
      investigate if this new measure, which would account for foot size, correlated
      well with an established measure (LAA) that estimated the behaviour of the arch
      with walking and running. Also, we hoped to contribute to the literature
      correlating longitudinal arch height with pain - numeric pain rating scale - and
      dysfunction - Lower Extremity Functional Scale (LEFS) and Single Assessment
      Numeric Evaluation (SANE). METHODS: Thirty-five subjects for this prospective
      correlational study were recruited from a community based outpatient practice
      that was part of a tertiary care academic medical centre. Reliability and
      validity of our investigator and of the mAR was first examined. We then examined
      the correlation of the clinical classification of arch height (high, normal, or
      low) produced by these two measures with each other. We also explored the
      correlation of multiple measures of dysfunction and pain with arch height.
      RESULTS: Intrarater reliability and validity of the LAA showed an intraclass
      correlation (ICC) of 0.978 and Pearson's correlation coefficient (PCC) of 0.885,
      respectively. Intrarater reliability and validity of the mAR showed an ICC of
      0.961 and PCC of 0.827, respectively. The LAA and our new measure, the mAR, were
      correlated with each other. The self-report measures of general health and
      activity level were significantly positively correlated (PCC = 0.598). Also
      significant and positively correlated were the LEFS and the SANE (PCC = 0.617),
      two measures of function. CONCLUSIONS: Pain and dysfunction may be positively
      correlated but longitudinal arch height does not predict either pain or
      dysfunction.

PMID- 20127667
TI  - Kinetic study of the formation of polypyrrole nanoparticles in water-soluble
      polymer/metal cation systems: a light-scattering analysis.
AB  - A facile way to synthesize nanometer-sized polymer (polypyrrole, PPy) particles
      is explored on the basis of the formation of complexes between water-soluble
      polymers and metal cations in aqueous solution. The metal cation is used as an
      oxidizing agent to initiate the chemical oxidation polymerization of the
      corresponding monomer, and the water-soluble polymer effectively provides a
      steric stability for the growth of polymer nanoparticles during the
      polymerization process. Light-scattering analyses are performed to give insight
      into the behavior of the complexes in aqueous solution. In addition, major
      physical parameters affecting the formation of polymer nanoparticles are
      investigated, including hydrodynamic radius, radius of gyration, shape factor,
      and viscosity. By judicious control of these parameters, PPy nanoparticles with
      narrow size distribution can be readily fabricated in large quantities. It is
      also possible to control the diameter of the nanoparticles by changing critical
      synthetic variables. Importantly, PPy nanoparticles of approximately 20-60 nm in
      diameter can be prepared without using any surfactants or specific templates;
      this novel strategy offers great possibility for mass production of polymer
      nanoparticles.

PMID- 20127668
TI  - Peptide nucleic acid films and capsules: assembly and enzymatic degradation.
AB  - Sequence-directed hybridization of nucleic acids provides a high level of control
      for the bottom-up assembly of nanostructured materials. Altering the DNA sequence
      affords control and versatility over the film structure, but is limited by the
      chemical and physical properties of DNA. Here, we use DNA analogues, peptide
      nucleic acids (PNAs), to introduce new properties to multilayered thin films and
      retain the advantages of sequence-directed assembly. Thin films, formed by the
      layer-by-layer (LbL) assembly of PNA strands, were assembled from short PNA
      sequences on planar and colloidal substrates. In the case of PNA-coated
      particles, hollow capsules were obtained following removal of the sacrificial
      particle template. The PNA films were stable to both nuclease and protease
      degradation, and the nuclease degradation rate could be tuned by varying the
      amount of DNA incorporated into the films. These thin films may find use in
      biomedical applications.

PMID- 20127669
TI  - Micellar nanocarriers assembled from doxorubicin-conjugated amphiphilic
      macromolecules (DOX-AM).
AB  - Amphiphilic macromolecules (AMs) have unique branched hydrophobic domains
      attached to linear PEG chains. AMs self-assemble in aqueous solution to form
      micelles that are hydrolytically stable in physiological conditions (37 degrees
      C, pH 7.4) over 4 weeks. Evidence of AM biodegradability was demonstrated by
      complete AM degradation after 6 d in the presence of lipase. Doxorubicin (DOX)
      was chemically conjugated to AMs via a hydrazone linker to form DOX-AM conjugates
      that self-assembled into micelles in aqueous solution. The conjugates were
      compared with DOX-loaded AM micelles (i.e., physically loaded DOX) on DOX
      content, micellar sizes and in vitro cytotoxicity. Physically encapsulated DOX
      loading was higher (12 wt.-%) than chemically bound DOX (6 wt.-%), and micellar
      sizes of DOX-loaded AMs (approximately 16 nm) were smaller than DOX-AMs
      (approximately 30 nm). In vitro DOX release from DOX-AM conjugates was faster at
      pH 5.0 (100%) compared to pH 7.4 (78%) after 48 h, 37 degrees C. Compared to free
      DOX and physically encapsulated DOX, chemically bound DOX had significantly
      higher cytotoxicity at 10(-7) M DOX dose against human hepatocellular carcinoma
      cells after 72 h. Overall, DOX-AM micelles showed promising characteristics as
      stable, biodegradable DOX nanocarriers.

PMID- 20127670
TI  - Triggered drug release from dynamic microspheres via a protein conformational
      change.
AB  - In this study we formed and characterized dynamic hydrogel microspheres in which
      a protein conformational change was used to control microsphere volume changes
      and the release of an encapsulated drug. In particular, a specific biochemical
      ligand, trifluoperazine, induced calmodulin's nanometer scale conformation
      change, which translated to a 48.7% microsphere volume decrease. This specific,
      ligand-induced volume change triggered the release of a model drug, vascular
      endothelial growth factor (VEGF), at pre-determined times. After release from the
      microspheres, 85.6 +/- 10.5% of VEGF was in its native conformation. Taken
      together, these results suggest that protein conformational change could serve as
      a useful mechanism to control drug release from dynamic hydrogels.

PMID- 20127671
TI  - Biocompatibility studies of functionalized regioregular poly(3-hexylthiophene)
      layers for sensing applications.
AB  - There is a significant medical and biological need for cheap disposable
      analytical sensing devices, which can be used in clinical settings or medical
      research. Organic electronics based on polymeric materials, being suitable for
      large-area, low-cost, flexible, and maybe even disposable electronics, could
      satisfy this need in a very elegant way. Unfortunately, the ensurance of
      biocompatibility and biofunctionalization of conducting and semiconducting
      polymers is still often lacking. In the present study, we concentrate on one of
      the most promising polymeric materials, regioregular poly(3-hexylthiophene)
      (P3HT), being both a reasonably conducting and optically active polymer. To
      overcome biocompatibility problems, protein-based coatings and oxygen-plasma
      treatments are performed to enable growth of adherent living cells on those
      modified surfaces. For our studies, the polymer material is spun or casted onto
      glass substrates under an inert nitrogen atmosphere. The toxic solvents are
      removed by thermal treatment with subsequent application of the coating or
      functionalizing materials. Cell-growth studies and adhesion experiments on the
      modified P3HT thin-film layers are carried out with mouse fibroblasts. This work
      demonstrates the biocompatibility and biofunctionalization of an active
      semiconducting organic polymer, hence opening new possibilities in the
      realization of biomedical test systems based on organic biosensors in life
      sciences.

PMID- 20127674
TI  - Parenchymal cells critically curtail cytotoxic T-cell responses by inducing Bim
      mediated apoptosis.
AB  - To develop cytolytic effector functions, CD8(+) T lymphocytes need to recognize
      specific Ag/MHC class I complexes in the context of costimuli on Ag-presenting
      DC. Thereafter they differentiate into effector and memory CTL able to confer
      protection against pathogen infection. Using transgenic mice with DC-selective
      MHC class I expression and DC-specific versus ubiquitous vaccination regimen, we
      found that DC are sufficient to prime CTL responses. However, Ag recognition on
      parenchymal non-professional APC negatively affected CD8(+) T-cell responses in
      mice by inducing expression of the pro-apoptotic bcl2-family member bim in CTL.
      This unexpected induction of apoptosis in the early phase of effector CTL
      accumulation lead to suboptimal clonal burst size and diminished long-term
      memory. Thus, our data demonstrate that effector CTL differentiation and
      apoptosis are regulated independently. Moreover, Ag distribution on cells other
      than DC critically reduces CTL responses.

PMID- 20127673
TI  - Thymic stromal lymphopoietin induces early human B-cell proliferation and
      differentiation.
AB  - Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL-7-receptor
      alpha chain and a unique TSLP receptor (TSLPR) chain. The role of TSLP in human B
      cell development has not been elucidated. We show that TSLPR transcripts are
      expressed most prominently in CD34(+) cells from fetal liver and BM. In general,
      cell surface expression of TSLPR was low, except on a subset of multilineage
      commited progenitor cells. TSLP induced the tyrosine-phosphorylation of STAT5 and
      the proliferation of multilineage-commited progenitor cells, pro-B cells and pre
      B cells. Compared with IL-7, the levels of proliferation after stimulation of the
      B-cell progenitors with TSLP were lower. Expression of the BCR on the cell
      surface of fetal cells was inversely correlated to TSLP or IL-7 responsiveness.
      Pre-B cells from fetal BM, but not fetal liver, were refractory to TSLP or IL-7
      stimulation. When employing an in vitro B-cell differentiation culture system
      starting from CD34(+)CD38(-) multipotent HSC, IL-7 induced a short wave of
      precursor cell expansion but did not result in long-term survival of mature B
      cells. TSLP was capable of increasing the proportion and the absolute numbers of
      more mature human B cells. Overall, we provide evidence that TSLP supports human
      B-cell differentiation from fetal hematopoietic progenitors.

PMID- 20127675
TI  - Targeted inhibition of IL-10-secreting CD25- Treg via p38 MAPK suppression in
      cancer immunotherapy.
AB  - Cancer-induced immunotolerance mediated by inducible Treg (iTreg) is a major
      obstacle to cancer immunotherapy. In a basic study of immunotolerance, injection
      of an endogenous superantigen, i.e. the minor lymphocyte stimulatory (Mls)-1(a),
      into specific TCR Vbeta8.1-Tg mice enabled generation of anergic CD25(-) iTreg,
      the immunosuppressive function of which was maintained by IL-10 production via
      p38-MAPK activation. Interestingly, although p38-chemical inhibitor (p38
      inhibitor) is capable of breaking CD25(-) iTreg-induced immunotolerance, the p38
      inhibitor had hardly any immunotolerance breaking effect when CD25(+) Treg were
      present, suggesting that depletion of CD25(+) Treg is necessary for p38-inhibitor
      to be effective. Peptide OVA(323-339) iv.-injection into its specific TCR-Tg (OT
      II) mice also induced adaptive tolerance by iTreg. Peptide immunotherapy with p38
      inhibitor after CD25(+) Treg-depletion was performed in an OVA-expressing
      lymphoma E.G7-bearing tolerant model established by adoptive transfer of OT-II
      CD25(-) iTreg, which resulted in suppression of tumor growth. Similarly, the
      antitumor immunity induced by peptide immunotherapy in colon carcinoma CT26
      bearing mice, in which the number of IL-10-secreting iTreg is increased, was
      augmented by treatment with p38-inhibitor after CD25(+) Treg-depletion and
      resulted in inhibition of tumor progression. These results suggest that
      simultaneous inhibition of two distinct Treg-functions may be important to the
      success of cancer immunotherapy.

PMID- 20127676
TI  - The cyclin-dependent kinase inhibitor R-roscovitine down-regulates Mcl-1 to
      override pro-inflammatory signalling and drive neutrophil apoptosis.
AB  - Successful resolution of inflammation requires inflammatory cells such as
      neutrophils to undergo apoptosis prior to non-inflammatory phagocytosis by
      professional phagocytes. Recently, cyclin-dependent kinase (CDK) inhibitors (e.g.
      R-roscovitine) have been shown to induce neutrophil apoptosis and enhance the
      resolution of inflammation. Interestingly, NF-kappaB and MAPK pathways and key
      endogenous survival proteins (typified by Mcl-1) are involved in the regulation
      of neutrophil apoptosis and, in cancer-cell lines, have been implicated as
      possible targets of CDK inhibitors. Here, we demonstrate that R-roscovitine over
      rides TNF-alpha and LPS-induced survival (determined by morphological examination
      and binding of fluorescently labelled annexin-V) of isolated peripheral blood
      neutrophils. This effect did not appear to be mediated via effects on early
      markers of neutrophil activation (e.g. surface marker expression, shape change,
      aggregation and superoxide anion generation), by direct inhibition of NF-kappaB
      activation (assessed by cytoplasmic IkappaBalpha proteolysis and NF-kappaB p65
      subunit translocation) and ERK activation (determined by specific ERK
      phosphorylation) but due to down-regulation (at protein and mRNA level) of the
      survival protein Mcl-1 but not the pro-apoptotic bcl-2 homologue Bim. These
      findings suggest that key endogenous survival proteins may be the targets of CDK
      inhibitors and consequently may be of critical importance in the resolution of
      inflammation.

PMID- 20127677
TI  - Impaired CD4+ T-cell proliferation and effector function correlates with
      repressive histone methylation events in a mouse model of severe sepsis.
AB  - Immunosuppression following severe sepsis remains a significant human health
      concern, as long-term morbidity and mortality rates of patients who have
      recovered from life-threatening septic shock remain poor. Mouse models of severe
      sepsis indicate this immunosuppression may be partly due to alterations in
      myeloid cell function; however, the effect of severe sepsis on subsequent CD4(+)
      T-cell responses remains unclear. In the present study, CD4(+) T cells from mice
      subjected to an experimental model of severe sepsis (cecal ligation and puncture
      (CLP)) were analyzed in vitro. CD4(+)CD62L(+) T cells from CLP mice exhibited
      reduced proliferative capacity and altered gene expression. Additionally,
      CD4(+)CD62L(+) T cells from CLP mice exhibit dysregulated cytokine production
      after in vitro skewing with exogenous cytokines, indicating a decreased
      capability of these cells to commit to either the T(H)1 or T(H)2 lineage.
      Repressive histone methylation marks were also evident at promoter regions for
      the T(H)1 cytokine IFN-gamma and the T(H)2 transcription factor GATA-3 in naive
      CD4(+) T cells from CLP mice. These results provide evidence that CD4(+) T-cell
      subsets from post-septic mice exhibit defects in activation and effector
      function, possibly due to chromatin remodeling proximal to genes involved in
      cytokine production or gene transcription.

PMID- 20127678
TI  - SUMOylation attenuates c-Maf-dependent IL-4 expression.
AB  - The function of transcription factors can be critically regulated by SUMOylation.
      c-Maf, the cellular counterpart of v-maf oncogene, is a potent transactivator of
      the IL-4 gene in Th2 cells. We found in a yeast two-hybrid screen that c-Maf can
      interact with Ubc9 and PIAS1, two key enzymes of the SUMOylation pathway. In this
      study, we report that c-Maf co-localized with these two SUMO (small ubiquitin
      like modifier) ligases in the nucleus and that c-Maf can be SUMOylated in vitro
      and also in primary Th2 cells. We also demonstrated that lysine-33 is the
      dominant, if not the only, SUMO acceptor site of c-Maf. SUMOylation of c-Maf
      attenuated its transcriptional activity. Reciprocally, a SUMOylation resistant c
      Maf was more potent than WT-c-Maf in driving IL-4 production in c-Maf-deficient
      Th2 cells. Furthermore, we showed that ablation of the SUMO site did not alter
      the subcellular localization or the stability of c-Maf protein but instead
      enhanced its recruitment to the Il4-promoter. We conclude that SUMOylation at
      lysine-33 is a functionally critical post-translational modification event of c
      Maf in Th cells.

PMID- 20127679
TI  - The DC-SIGN family member LSECtin is a novel ligand of CD44 on activated T cells.
AB  - LSECtin, a novel member of the C-type lectin DC-SIGN family, not only acts as an
      attachment factor for pathogens, but also recognizes "endogenous" activated T
      cells. The endogenous ligands of LSECtin, however, have remained unclear. In this
      study, we identified CD44 on Jurkat T cells as a candidate ligand of LSECtin, and
      confirmed the specific interaction between LSECtin and CD44. Moreover, we showed
      that LSECtin selectively bound CD44s, CD44v4 and CD44v8-10 by screening a series
      of typical CD44 isoforms. By deletion of the carbohydrate-recognition domain
      region and mutation of crucial amino acids involved in carbohydrate-recognition
      of LSECtin and by inhibition of the N-linked glycosylation of CD44, we further
      demonstrated that the interaction between CD44 and LSECtin is dependent on
      protein-glycan recognition. Our findings indicate that CD44 is the first
      identified endogenous ligand of LSECtin, and similarly, that LSECtin is a novel
      ligand of CD44. These findings provide important new perspectives on the biology
      of both LSECtin and CD44 in the immune system.

PMID- 20127680
TI  - Co-expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+
      regulatory T cells in human peripheral blood.
AB  - Previously, we found that co-expression of CD25 and TNFR2 identified the most
      suppressive subset of mouse Treg. In this study, we report that human peripheral
      blood (PB) FOXP3(+) cells present in CD25(high), CD25(low) and even CD25(-)
      subsets of CD4(+) cells expressed high levels of TNFR2. Consequently, TNFR2
      expressing CD4(+)CD25(+) Treg included all of the FOXP3(+) cells present in the
      CD4(+)CD25(high) subset as well as a substantial proportion of the FOXP3(+) cells
      present in the CD4(+)CD25(low) subset. Flow cytometric analysis of PB identified
      five-fold more Treg, determined by FOXP3 expression, in the CD4(+)CD25(+)TNFR2(+)
      subset than in the CD4(+)CD25(high) subset. In addition, similar levels of
      FOXP3(+) cells were identified in both the CD4(+)CD25(+)TNFR2(+) and
      CD4(+)CD25(+)CD127(low/-) subsets. Furthermore, the CD4(+)CD25(+)TNFR2(+) subset
      expressed high levels of CTLA-4, CD45RO, CCR4 and low levels of CD45RA and CD127,
      a phenotype characteristic of Treg. Upon TCR stimulation, human PB
      CD4(+)CD25(+)TNFR2(+) cells were anergic and markedly inhibited the proliferation
      and cytokine production of co-cultured T-responder cells. In contrast,
      CD4(+)CD25(+)TNFR2(-) and CD4(+)CD25(-)TNFR2(+) T cells did not show inhibitory
      activity. As some non-Treg express TNFR2, the combination of CD25 and TNFR2 must
      be used to identify a larger population of human Treg, a population that may
      prove to be of diagnostic and therapeutic benefit in cancer and autoimmune
      diseases.

PMID- 20127681
TI  - DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN
      beta-inducing potential.
AB  - Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLR) are members of the
      DEAD box helicases, and recognize viral RNA in the cytoplasm, leading to IFN-beta
      induction through the adaptor IFN-beta promoter stimulator-1 (IPS-1) (also known
      as Cardif, mitochondrial antiviral signaling protein or virus-induced signaling
      adaptor). Since uninfected cells usually harbor a trace of RIG-I, other RNA
      binding proteins may participate in assembling viral RNA into the IPS-1 pathway
      during the initial response to infection. We searched for proteins coupling with
      human IPS-1 by yeast two-hybrid and identified another DEAD (Asp-Glu-Ala-Asp) box
      helicase, DDX3 (DEAD/H BOX 3). DDX3 can bind viral RNA to join it in the IPS-1
      complex. Unlike RIG-I, DDX3 was constitutively expressed in cells, and some
      fraction of DDX3 is colocalized with IPS-1 around mitochondria. The 622-662 a.a
      DDX3 C-terminal region (DDX3-C) directly bound to the IPS-1 CARD-like domain, and
      the whole DDX3 protein also associated with RLR. By reporter assay, DDX3 helped
      IPS-1 up-regulate IFN-beta promoter activation and knockdown of DDX3 by siRNA
      resulted in reduced IFN-beta induction. This activity was conserved on the DDX3-C
      fragment. DDX3 only marginally enhanced IFN-beta promoter activation induced by
      transfected TANK-binding kinase 1 (TBK1) or I-kappa-B kinase-epsilon
      (IKKepsilon). Forced expression of DDX3 augmented virus-mediated IFN-beta
      induction and host cell protection against virus infection. Hence, DDX3 is an
      antiviral IPS-1 enhancer.

PMID- 20127682
TI  - Verification of protein disulfide bond arrangement by in-gel tryptic digestion
      under entirely neutral pH conditions.
AB  - To develop a concise proteomic procedure to verify the protein disulfide bond
      arrangement, non-reductive trypsin digestion of neuregulin 1-beta1 (176-246), a
      model disulfide-containing protein, was assessed by a proteolytic (18)O-labeling
      analysis. As a result, the commonly used in-gel tryptic digestion method has been
      improved for use entirely under neutral pH conditions. With this procedure, the
      disulfide arrangement of proteins could represent a clinical index candidate in
      pathological proteomic studies.

PMID- 20127683
TI  - Using a cross-model loadings plot to identify protein spots causing 2-DE gels to
      become outliers in PCA.
AB  - The multivariate method PCA is an exploratory tool often used to get an overview
      of multivariate data, such as the quantified spot volumes of digitized 2-DE gels.
      PCA can reveal hidden structures present in the data, and thus enables
      identification of potential outliers and clustering. Based on PCA, we here
      present an approach for identification of protein spots causing 2-DE gels to
      become outliers. The approach can potentially obviate analytical exclusion of
      entire 2-DE gels.

PMID- 20127685
TI  - Comparison of protein enrichment strategies for proteome analysis of plasma.
AB  - Efforts to discover protein biomarkers in plasma are hampered by the high
      abundance of few proteins, which interfere with the detection of low-abundant
      proteins. Different commercially available protein-partitioning products were
      tested for their ability to lower the detection limit of proteins in 2-D gels.
      Immuno-depletion using polyclonal antibodies raised against the proteins of
      highest abundance (Seppro IgY14 System) was compared with a two-step immuno
      depletion strategy, where depletion with the Seppro IgY14 column was followed by
      depletion with the Seppro IgY-SuperMix system. The third strategy tested was
      protein pre-fractionation using the ProteoMiner kit, where proteins compete for
      binding sites on bead-bound peptide hexamers with different binding properties.
      The pre-fractionated protein samples were analyzed using 2-DE, which revealed
      stunning differences in protein patterns. However, detectable protein spots in
      the different plasma fractions contained exclusively high-abundant proteins
      normally present in plasma at concentrations between 1 microg and 40 mg/mL.

PMID- 20127684
TI  - Pathway analysis of dilated cardiomyopathy using global proteomic profiling and
      enrichment maps.
AB  - Global protein expression profiling can potentially uncover perturbations
      associated with common forms of heart disease. We have used shotgun MS/MS to
      monitor the state of biological systems in cardiac tissue correlating with
      disease onset, cardiac insufficiency and progression to heart failure in a time
      course mouse model of dilated cardiomyopathy. However, interpreting the
      functional significance of the hundreds of differentially expressed proteins has
      been challenging. Here, we utilize improved enrichment statistical methods and an
      extensive collection of functionally related gene sets, gaining a more
      comprehensive understanding of the progressive alterations associated with
      functional decline in dilated cardiomyopathy. We visualize the enrichment results
      as an Enrichment Map, where significant gene sets are grouped based on annotation
      similarity. This approach vastly simplifies the interpretation of the large
      number of enriched gene sets found. For pathways of specific interest, such as
      Apoptosis and the MAPK (mitogen-activated protein kinase) cascade, we performed a
      more detailed analysis of the underlying signaling network, including
      experimental validation of expression patterns.

PMID- 20127686
TI  - Protein subcellular localization profiling of breast cancer cells by dissociable
      antibody microarray staining.
AB  - We have developed dissociable antibody microarray (DAMA) staining technology that
      provides a new approach to the global analysis of protein subcellular
      localization (SCL) in fixed cells. We have developed and optimized this
      technology for protein SCL profiling, generated ChipView, a program for
      management and analysis of molecular image database, and utilized the technique
      to identify proteins with unique SCL in breast cancer cell lines. We compared the
      SCL profiles of 325 proteins among nine different breast cell lines, and have
      identified one protein, Cyclin B1, with distinctively different SCLs between
      normal and cancer cell lines. With classic individual immunostaining, Cyclin B1
      was confirmed to localize to the cytoplasm of seven breast cancer cell lines and
      in both cytoplasm and nuclei of two normal breast cell lines, and to have higher
      expression levels in the cancer cell lines tested.

PMID- 20127687
TI  - Effects of thawing, refreezing and storage conditions of tissue samples and
      protein extracts on 2-DE spot intensity.
AB  - We report that reliable quantitative proteome analyses can be performed with
      tissue samples stored at -80 degrees C for up to 10 years. However, storing
      protein extracts at 4 degrees C for 24 h and freezing protein extracts at -80
      degrees C and thawing them significantly altered 41.6 and 17.5% of all spot
      intensities on 2-DE gels, respectively. Fortunately, these storing effects did
      not impair the reliability of quantifying 2-DE experiments. Nonetheless, the
      results show that freezing and storage conditions should be carefully controlled
      in proteomic experiments.

PMID- 20127688
TI  - Increased interaction between DJ-1 and the Mi-2/ nucleosome remodelling and
      deacetylase complex during cellular stress.
AB  - DJ-1 was originally identified to be an oncogenic product, but has later been
      shown to be highly multifunctional. DJ-1 plays a role in oxidative stress
      response and transcriptional regulation, and loss of its function leads to an
      early onset of Parkinsonism. To further understand the mechanisms behind DJ-1's
      role in cell survival and death, we investigated alternations in endogenous DJ-1
      protein-protein interaction in apoptotic cells exposed to the phosphatase
      inhibitor okadaic acid. By combining cellular stable isotopic labelling of amino
      acids in cell culture, sub-cellular fractionation, co-immunoprecipitation, and
      MS, we identified a novel group of DJ-1 interaction partners that increased their
      association to DJ-1 in okadaic acid-exposed cells. These proteins were integral
      components of the Mi-2/nucleosome remodelling and deacetylase (NuRD) complex.
      Knockdown of DJ-1 and MTA2, a core component of the NuRD complex, had a similar
      and pro-apoptotic effect on the transcriptional- and p53-dependent cell death
      induced by daunorubicin. On the other hand, MTA2 knockdown had no significant
      effect on the progression of p53-independent okadaic acid-induced apoptosis. Our
      data suggest that the increased DJ-1/NuRD interaction is a general anti-stress
      response regulated by okadaic acid-induced modifications of DJ-1. The observed
      interaction between DJ-1 and the NuRD complex may give new clues to how DJ-1 can
      protect cells from p53-dependent cell death.

PMID- 20127689
TI  - Protein-protein-interactions in a multiplexed, miniaturized format a functional
      analysis of Rho GTPase activation and inhibition.
AB  - A miniaturized, bead-based protein-protein-interaction assay was developed to
      study the interaction of Rho GTPases with regulatory proteins. The setup, which
      uses only minute amounts of sample, was used to analyze small molecules that
      inhibit the interaction between Rho GTPases and RhoGDI alpha. Prenylcysteine
      analogues and the replacement of GDP by non-hydrolysable GTP analogues prevented
      the formation of Rho GTPase-RhoGDI alpha complexes in a concentration-dependent
      manner.

PMID- 20127690
TI  - Proteomics of drug resistance in Candida glabrata biofilms.
AB  - Candida glabrata is a fungal pathogen that causes a variety of mucosal and
      systemic infections among compromised patient populations with higher mortality
      rates. Previous studies have shown that biofilm mode of the growth of the fungus
      is highly resistant to antifungal agents compared with the free-floating or
      planktonic mode of growth. Therefore, in the present study, we used 2-D DIGE to
      evaluate the differential proteomic profiles of C. glabrata under planktonic and
      biofilm modes of growth. Candida glabrata biofilms were developed on polystyrene
      surfaces and age-matched planktonic cultures were obtained in parallel.
      Initially, biofilm architecture, viability, and antifungal susceptibility were
      evaluated. Differentially expressed proteins more than 1.5-fold in DIGE analysis
      were subjected to MS/MS. The transcriptomic regulation of these biomarkers was
      evaluated by quantitative real-time PCR. Candida glabrata biofilms were highly
      resistant to the antifungals and biocides compared with the planktonic mode of
      growth. Candida glabrata biofilm proteome when compared with its planktonic
      proteome showed upregulation of stress response proteins, while glycolysis
      enzymes were downregulated. Similar trend could be observed at transcriptomic
      level. In conclusion, C. glabrata biofilms possess higher amount of stress
      response proteins, which may potentially contribute to the higher antifungal
      resistance seen in C. glabrata biofilms.

PMID- 20127691
TI  - Honokiol inhibits HepG2 migration via down-regulation of IQGAP1 expression
      discovered by a quantitative pharmaceutical proteomic analysis.
AB  - Honokiol (HNK), a natural small molecular product, inhibited proliferation of
      HepG2 cells and exhibited anti-tumor activity in nude mice. In this article, we
      applied a novel sensitive stable isotope labeling with amino acids in cell
      culture-based quantitative proteomic method and a model of nude mice to
      investigate the correlation between HNK and the hotspot migration molecule Ras
      GTPase-activating-like protein (IQGAP1). The quantitative proteomic analysis
      showed that IQGAP1 was 0.53-fold down-regulated under 10 microg/mL HNK exposure
      for 24 h on HepG2 cells. Migration ability of HepG2 cells under HNK treatment was
      correlated with its expression level of IQGAP1. In addition, the biochemical
      validation on HepG2 cells and the tumor xenograft model further demonstrated that
      HNK decreased the expression level of IQGAP1 and its upstream proteins
      Cdc42/Rac1. These data supported that HNK can modulate cell adhesion and cell
      migration by acting on Cdc42/Rac1 signaling via IQGAP1 interactions with its
      upstream Cdc42/Rac1 proteins, which is a new molecular mechanism of HNK to exert
      its anti-tumor activity.

PMID- 20127692
TI  - False labelling due to quenching failure of N-hydroxy-succinimide-ester-coupled
      dyes.
AB  - In comparative fluorescence gel electrophoresis experiments, cross-talk was
      detected. It was traced back to a failure in the quenching process in typical
      labelling protocols. Despite a huge excess of potential reaction sites for the N
      hydroxy-succinimide-ester-coupled dye, sufficient active dye molecules were
      available after the quenching step to label protein molecules un-specifically. It
      could be shown that only a 100-fold increase in the amount of quencher will
      silence residual dye to such an extent that no artificial signals are detected.

PMID- 20127693
TI  - jmzML, an open-source Java API for mzML, the PSI standard for MS data.
AB  - We here present jmzML, a Java API for the Proteomics Standards Initiative mzML
      data standard. Based on the Java Architecture for XML Binding and XPath-based XML
      indexer random-access XML parser, jmzML can handle arbitrarily large files in
      minimal memory, allowing easy and efficient processing of mzML files using the
      Java programming language. jmzML also automatically resolves internal XML
      references on-the-fly. The library (which includes a viewer) can be downloaded
      from http://jmzml.googlecode.com.

PMID- 20127694
TI  - Laser-induced liquid bead ion desorption-MS of protein complexes from blue-native
      gels, a sensitive top-down proteomic approach.
AB  - We have developed an experimental approach that combines two powerful methods for
      proteomic analysis of large membrane protein complexes: blue native
      electrophoresis (BNE or BN-PAGE) and laser-induced liquid bead ion desorption
      (LILBID) MS. Protein complexes were separated by BNE and eluted from the gel. The
      masses of the constituents of the multiprotein complexes were obtained by LILBID
      MS, a detergent-tolerant method that is especially suitable for the
      characterisation of membrane proteins. High sensitivity and small sample volumes
      required for LILBID MS resulted in low demands on sample quantity. Eluate from a
      single band allowed assessing the mass of an entire multiprotein complex and its
      subunits. The method was validated with mitochondrial NADH:ubiquinone reductase
      from Yarrowia lipolytica. For this complex of 947 kDa, typically 30 microg or 32
      pmol were sufficient to obtain spectra from which the subunit composition could
      be analysed. The resolution of this electrophoretic small-scale approach to the
      purification of native complexes was improved markedly by further separation on a
      second dimension of BNE. Starting from a subcellular fraction obtained by
      differential centrifugation, this allowed the purification and analysis of the
      constituents of a large multiprotein complex in a single LILBID spectrum.

PMID- 20127695
TI  - Proteomic identification of interactions between histones and plasma proteins:
      implications for cytoprotection.
AB  - Extracellular histones released from cells during acute inflammation contribute
      to organ failure and death in a mouse model of sepsis, and histones are known to
      exert in vitro cytotoxicity in the absence of serum. Since addition of histones
      to serum and plasma is known to induce protein aggregation, we reasoned that
      plasma proteins may afford protection from cytotoxicity. We found that MODE-K
      mouse small intestinal epithelial cells were protected from histone-induced
      toxicity in the presence of 10% FCS. Therefore, the main aim of this study was to
      identify histone-interacting plasma proteins that might be involved in
      cytoprotection. The precipitate formed following addition of calf thymus histones
      to human EDTA plasma was characterised by shotgun proteomics, identifying a total
      of 36 protein subunits, including complement components, coagulation factors,
      protease inhibitors and apolipoproteins. The highly sulphated glycosaminoglycan
      heparin inhibited histone-induced plasma protein aggregation. Moreover, histones
      bound to heparin agarose were capable of pulling down plasma proteins from
      solution, indicating their effective cross-linking properties. It was
      particularly notable that inter-alpha-trypsin inhibitor was prominent among the
      histone-precipitated proteins, since it contains a chondroitin sulphate glycan
      chain, and suggests a potential role for this protein in histone sequestration
      during acute inflammation in vivo.

PMID- 20127696
TI  - Stimulated single-cell force spectroscopy to quantify cell adhesion receptor
      crosstalk.
AB  - To control their attachment to substrates and other cells, cells regulate their
      adhesion receptors. One regulatory process is receptor crosstalk, where the
      binding of one type of cell adhesion molecule influences the activity of another
      type. To identify such crosstalk and gain insight into their mechanisms, we
      developed the stimulated single-cell force spectroscopy assay. In this assay, the
      influence of a cells adhesion to one substrate on the strength of its adhesion to
      a second substrate is examined. The assay quantifies the adhesion of the cell and
      the contributions of specific adhesion receptors. This allows mechanisms by which
      the adhesion is regulated to be determined. Using the assay we identified
      crosstalk between collagen-binding integrin alpha(1)beta(1) and fibronectin
      binding integrin alpha(5)beta(1) in HeLa cells. This crosstalk was
      unidirectional, from integrin alpha(1)beta(1) to integrin alpha(5)beta(1), and
      functioned by regulating the endocytosis of integrin alpha(5)beta(1). The single
      cell assay should be expandable for the screening and quantification of crosstalk
      between various cell adhesion molecules and other cell surface receptors.

PMID- 20127697
TI  - Selective separation and enrichment of peptides for MS analysis using the
      microspheres composed of Fe3O4@nSiO2 core and perpendicularly aligned mesoporous
      SiO2 shell.
AB  - In this work, we report the development of a novel enrichment protocol for
      peptides by using the microspheres composed of Fe(3)O(4)@nSiO(2) Core and
      perpendicularly aligned mesoporous SiO(2) shell (designated
      Fe(3)O(4)@nSiO(2)@mSiO(2)). The Fe(3)O(4)@nSiO(2)@mSiO(2) microspheres possess
      useful magnetic responsivity which makes the process of enrichment fast and
      convenient. The highly ordered nanoscale pores (2 nm) and high-surface areas of
      the microspheres were demonstrated to have good size-exclusion effect for the
      adsorption of peptides. An increase of S/N ratio over 100 times could be achieved
      by using the microspheres to enrich a standard peptide, and the application of
      the microspheres to enrich universal peptides was performed by using myoglobin
      tryptic digest solution. The enrichment efficiency of re-used
      Fe(3)O(4)@nSiO(2)@mSiO(2) microspheres was also studied. Large-scale enrichment
      of endogenous peptides in rat brain extract was achieved by the microspheres.
      Automated nano-LC-ESI-MS/MS was applied to analyze the sample after enrichment,
      and 60 unique peptides were identified in total. The facile and low-cost
      synthesis as well as the convenient and efficient enrichment process of the novel
      Fe(3)O(4)@nSiO(2)@mSiO(2) microspheres makes it a promising candidate for
      selectively isolation and enrichment of endogenous peptides from complex
      biological samples.

PMID- 20127698
TI  - Effects of dyslexia on postural control in adults.
AB  - Dyslexia has been shown to affect postural control. The aim of the present study
      was to investigate the difference in postural stability measured as torque
      variance in an adult dyslexic group (n=14, determined using the Adult Dyslexia
      Checklist (ADCL) and nonsense word repetition test) and an adult non-dyslexic
      group (n=39) on a firm surface and on a foam block and with eyes open and eyes
      closed. Another aim was to investigate the correlation between ADCL scores and
      postural stability. Findings showed that ADCL scores correlated with torque
      variance in the anteroposterior direction on foam with eyes closed (p=0.001) and
      in the lateral direction on the foam surface with eyes closed (p=0.040) and open
      (p=0.010). General Linear Model analysis showed that high dyslexia scores were
      associated with increased torque variance (p<0.001). However, we found no
      significant difference between dyslexics and non-dyslexics, though there were
      indications of larger torque variance in the dyslexics. The findings suggest that
      adults with high dyslexic ADCL scores may experience sub-clinical balance
      deficits. Hence, assessing motor ability and postural control in those with high
      ADCL scores is motivated.

PMID- 20127699
TI  - Imaginal discs: Renaissance of a model for regenerative biology.
AB  - Many animals display a capacity to regenerate tissues or even a complete body.
      One of the main goals of regenerative biology is to identify the genes and
      genetic networks necessary for this process. Drosophila offers an ideal model
      system for such studies. The wide range of genetic and genomic approaches
      available for use in flies has helped in initiating the deciphering of the
      mechanisms underlying regeneration, and the results may be applicable to other
      organisms, including mammals. Moreover, most models of regeneration require
      experimental manipulation, whereas in Drosophila discrete domains can be ablated
      by genetically induced methods. Here, we present a summary of current research
      into imaginal disc regeneration and discuss the power of this tissue as a tool
      for understanding the genetics of regeneration.

PMID- 20127700
TI  - Improved network performance via antagonism: From synthetic rescues to multi-drug
      combinations.
AB  - Recent research shows that a faulty or sub-optimally operating metabolic network
      can often be rescued by the targeted removal of enzyme-coding genes - the exact
      opposite of what traditional gene therapy would suggest. Predictions go as far as
      to assert that certain gene knockouts can restore the growth of otherwise
      nonviable gene-deficient cells. Many questions follow from this discovery: What
      are the underlying mechanisms? How generalizable is this effect? What are the
      potential applications? Here, I approach these questions from the perspective of
      compensatory perturbations on networks. Relations are drawn between such
      synthetic rescues and naturally occurring cascades of reaction inactivation, as
      well as their analogs in physical and other biological networks. I specially
      discuss how rescue interactions can lead to the rational design of antagonistic
      drug combinations that select against resistance and how they can illuminate
      medical research on cancer, antibiotics, and metabolic diseases.

PMID- 20127701
TI  - When metabolism meets topology: Reconciling metabolite and reaction networks.
AB  - The search for a systems-level picture of metabolism as a web of molecular
      interactions provides a paradigmatic example of how the methods used to
      characterize a system can bias the interpretation of its functional meaning.
      Metabolic maps have been analyzed using novel techniques from network theory,
      revealing some non-trivial, functionally relevant properties. These include a
      small-world structure and hierarchical modularity. However, as discussed here,
      some of these properties might actually result from an inappropriate way of
      defining network interactions. Starting from the so-called bipartite organization
      of metabolism, where the two meaningful subsets (reactions and metabolites) are
      considered, most current works use only one of the subsets by means of so-called
      graph projections. Unfortunately, projected graphs often ignore relevant
      biological and chemical constraints, thus leading to statistical artifacts. Some
      of these drawbacks and alternative approaches need to be properly addressed.

PMID- 20127703
TI  - Electrophoresis today and tomorrow: Helping biologists' dreams come true.
AB  - Intensive research and development of electrophoresis methodology and
      instrumentation during past decades has resulted in unique methods widely
      implemented in bioanalysis. While two-dimensional electrophoresis and denaturing
      polyacrylamide gel electrophoresis in sodium dodecylsulfate are still the most
      frequently used electrophoretic methods applied to analyses of proteins, new
      miniaturized capillary and microfluidic versions of electromigrational methods
      have been developed. High-throughput electrophoretic instruments with hundreds of
      capillaries for parallel separations and laser-induced fluorescence detection of
      labeled DNA strands have been of key importance for the scientific and commercial
      success of the Human Genome Project. Another powerful method, capillary
      isoelectric focusing with pressurized and pH-driven mobilization, provides
      efficient separations and on-line sensitive detection of proteins, bacteria and
      viruses. Electrophoretic microfluidic devices can integrate single-cell
      injection, cell lysis, separation of its components and fluorescence or mass
      spectrometry detection. These miniaturized devices also proved the capability of
      single-molecule detection.

PMID- 20127704
TI  - Conjugated-polyelectrolyte-functionalized reduced graphene oxide with excellent
      solubility and stability in polar solvents.
AB  - Conjugated-polyelectrolyte (CPE)-functionalized reduced graphene oxide (rGO)
      sheets are synthesized for the first time by taking advantage of a specially
      designed CPE, PFVSO(3), with a planar backbone and charged sulfonate and
      oligo(ethylene glycol) side chains to assist the hydrazine-mediated reduction of
      graphene oxide (GO) in aqueous solution. The resulting CPE-functionalized rGO
      (PFVSO(3)-rGO) shows excellent solubility and stability in a variety of polar
      solvents, including water, ethanol, methanol, dimethyl sulfoxide, and dimethyl
      formamide. The morphology of PFVSO(3)-rGO is studied by atomic force microscopy,
      X-ray diffraction, and transmission electron microscopy, which reveal a sandwich
      like nanostructure. Within this nanostructure, the backbones of PFVSO(3) stack
      onto the basal plane of rGO sheets via strong pi-pi interactions, while the
      charged hydrophilic side chains of PFVSO(3) prevent the rGO sheets from
      aggregating via electrostatic and steric repulsions, thus leading to the
      solubility and stability of PFVSO(3)-rGO in polar solvents. Optoelectronic
      studies show that the presence of PFVSO(3) within rGO induces photoinduced charge
      transfer and p-doping of rGO. As a result, the electrical conductivity of
      PFVSO(3)-rGO is not only much better than that of GO, but also than that of the
      unmodified rGO.

PMID- 20127702
TI  - Mechanisms in dominant parkinsonism: The toxic triangle of LRRK2, alpha
      synuclein, and tau.
AB  - Parkinson's disease (PD) is generally sporadic but a number of genetic diseases
      have parkinsonism as a clinical feature. Two dominant genes, alpha-synuclein
      (SNCA) and leucine-rich repeat kinase 2 (LRRK2), are important for understanding
      inherited and sporadic PD. SNCA is a major component of pathologic inclusions
      termed Lewy bodies found in PD. LRRK2 is found in a significant proportion of PD
      cases. These two proteins may be linked as most LRRK2 PD cases have SNCA-positive
      Lewy bodies. Mutations in both proteins are associated with toxic effects in
      model systems although mechanisms are unclear. LRRK2 is an intracellular
      signaling protein possessing both GTPase and kinase activities that may
      contribute to pathogenicity. A third protein, tau, is implicated as a risk factor
      for PD. We discuss the potential relationship between these genes and suggest a
      model for PD pathogenesis where LRRK2 is upstream of pathogenic effects through
      SNCA, tau, or both proteins.

PMID- 20127705
TI  - Epigenetically regulated clonal heritability of CTA expression profiles in human
      melanoma.
AB  - The intratumoral heterogeneity of cancer testis antigens (CTA) expression, which
      is driven by promoter methylation status, may hamper the effectiveness of CTA
      directed vaccination of melanoma patients. Thus, we investigated whether the
      intratumoral heterogeneity of CTA expression is inherited at cellular level, or
      evolves throughout cellular replication, leading to a phenotypically unstable
      tumor cell population with reduced immunogenicity and/or able to escape immune
      control. Utilizing a previously characterized ex vivo clonal model of
      intratumoral heterogeneity of CTA expression in melanoma, Mel 313 MAGE-A3-low
      clone 5 (clone 5(M3-low)) and MAGE-A3-high clone 14 (clone 14(M3-high)) were sub
      cloned and analyzed for CTA profile. Molecular assays demonstrated that levels of
      MAGE-A3 expression were highly conserved among generated sub-clones, as compared
      to parental clones. A similar behavior was identified for an extensive panel of
      other CTA investigated. Inherited levels of MAGE-A3 expression correlated with
      the extent of promoter methylation among clone 5(M3-low) and clone 14(M3-high)
      sub-clones analyzed. Treatment of clone 5(M3-low) with a DNA hypomethylating
      agent (DHA) resulted in an up-regulated expression of MAGE-A3, which was
      inherited at single cell level, being still detectable at day 60 in its sub
      clones. Bisulfite sequencing demonstrated that also MAGE-A3 promoter methylation
      status was inherited among sub-clones generated from DHA-treated clone 5(M3-low)
      and strictly correlated with MAGE-A3 expression levels in investigated sub
      clones. Similar results were obtained for additional CTA studied. Altogether our
      findings demonstrate that constitutive and DHA-modified CTA profiles of melanoma
      cells are clonally inherited throughout cellular replications, thus providing
      relevant insights to improve the effectiveness of CTA-based immunotherapy.

PMID- 20127706
TI  - Cell signaling and cancer-possible targets for therapy.
AB  - Tumor progression involves the acquisition of properties which include growth
      factor independent cell proliferation, failure of inhibition by growth-inhibitory
      signals, ability to invade surrounding tissues, and to evade apoptosis, etc.
      Characterization of the profile or molecular signature of the tumor may permit
      the development of rational therapies that target the aberrant pathways. Rapidly
      growing tumor cells are usually associated with a high rates of glycolysis and in
      these cells, it may be advantageous to exploit this pathway which most likely is
      required for optimal synthetic needs. Combinatorial therapeutic agents which
      target the growth factor signal transduction pathways as well as apoptotic
      signaling pathways provide an opportunity for maximal therapeutic benefit.

PMID- 20127707
TI  - Decreased levels of Cx43 gap junctions result in ameloblast dysregulation and
      enamel hypoplasia in Gja1Jrt/+ mice.
AB  - Coordinated differentiation of the ameloblast cell layer is essential to enamel
      matrix protein deposition and subsequent mineralization. It has been hypothesized
      that this process is governed by Cx43-based gap junctional intercellular
      communication as oculodentodigital dysplasia (ODDD) patients harboring autosomal
      dominant mutations in Cx43 exhibit enamel defects typically resulting in early
      adulthood tooth loss. To assess the role of Cx43 in tooth development we employ a
      mouse model of ODDD that harbors a G60S Cx43 mutant, Gja1(Jrt)/+, and appears to
      exhibit tooth abnormalities that mimic the human disease. We found that total
      Cx43 plaques at all stages of ameloblast differentiation, as well as within the
      supporting cell layers, were greatly reduced in Gja1(Jrt)/+ incisors compared to
      wild-type littermate controls. To characterize the Gja1(Jrt)/+ mouse tooth
      phenotype, mice were sacrificed prior to tooth eruption (postnatal day 7),
      weaning (postnatal day 21), and adulthood (2 months postnatal). A severely
      disorganized Gja1(Jrt)/+ mouse ameloblast layer and abnormal accumulation of
      amelogenin were observed at stages when the cells were active in secretion and
      mineralization. Differences in enamel thickness became more apparent after tooth
      eruption and incisor exposure to the oral cavity suggesting that enamel integrity
      is compromised, leading to rapid erosion. Additional analysis of incisors from
      mutant mice revealed that they were longer with a thicker dentin layer than their
      wild-type littermates, which may reflect a mechanical stress response to the
      depleted enamel layer. Together, these data show that reduced levels of Cx43 gap
      junctions result in ameloblast dysregulation, enamel hypoplasia, and secondary
      tissue responses.

PMID- 20127708
TI  - Proteomic analysis of early-response to mechanical stress in neonatal rat
      mandibular condylar chondrocytes.
AB  - The objectives of this study were to investigate the early response to mechanical
      stress in neonatal rat mandibular chondrocytes by proteomic analysis. To evaluate
      its molecular mechanism, chondrocytes were isolated and cultured in vitro, then
      loaded mechanical stress by four-point bending system on different patterns.
      Morphological observation, flow cytometric analysis, and MTT assays indicated
      that 4,000 microstrain loading for 60 min was an appropriate mechanical stimulus
      for the following proteome analysis, which produced a transient but obvious
      inhibitory effect on the cell cycle. Therefore, we took a proteomic approach to
      identify significantly differential expression proteins in chondrocytes under
      this mechanical stress. Using 2-DE and MALDI-TOF, we identified seven
      differentially expressed proteins including the MAPK pathway inhibitor RKIP,
      cytoskeleton proteins, actin and vimentin, and other selected proteins. Some
      differentially expressed proteins were validated by both Western blot analysis
      and fluorescent staining of cytoskeleton at different loading times. The vimentin
      and RKIP responsive expression were also proven in vivo in oral orthopedic
      treatment rats, which was in line with the result in vitro. The histological
      changes in cartilage also showed the inhibition effect. Furthermore, the
      expressional level of phosphorylated ERK was increased, which demonstrates the
      changes in MAPK activity. Taken together, these data indicate that mechanical
      stress resulted in vimentin expression changes first and then led to the
      subsequent changes in actin expression, MAPK pathway regulated by RKIP and heat
      shock protein GRP75. All those changes contributed to the cytoskeleton remolding
      and cell cycle inhibition, finally led to condylar remodeling.

PMID- 20127709
TI  - Overexpression of Par-4 sensitizes TRAIL-induced apoptosis via inactivation of NF
      kappaB and Akt signaling pathways in renal cancer cells.
AB  - The prostate-apoptosis-response-gene-4 (Par-4) is up-regulated in prostate cells
      undergoing programmed cell death. Furthermore, Par-4 protein has been shown to
      function as an effector of cell death in response to various apoptotic stimuli
      that trigger mitochondria and membrane receptor-mediated cell death pathways. In
      this study, we investigated how Par-4 modulates TRAIL-mediated apoptosis in TRAIL
      resistant Caki cells. Par-4 overexpressing cells were strikingly sensitive to
      apoptosis induced by TRAIL compared with control cells. Par-4 overexpressing Caki
      cells treated with TRAIL showed an increased activation of the initiator caspase
      8 and the effector caspase-3, together with an enforced cleavage of XIAP and c
      FLIP. TRAIL-induced reduction of XIAP and c-FLIP protein levels in Par-4
      overexpressing cells was prevented by z-VAD pretreatment. In addition, the
      surface DR5 protein level was increased in TRAIL-treated Par-4 overexpressing
      cells. Interestingly, even though a deletion of leucine zipper domain in Par-4
      recovered Bcl-2 level to basal level induced by wild type Par-4, it partly
      decreased sensitivity to TRAIL in Caki cells. In addition, exposure of Caki/Par-4
      cells to TRAIL led to reduction of phosphorylated Akt levels, but deletion of
      leucine zipper domain of Par-4 did not affect these phosphorylated Akt levels. In
      conclusion, we here provide evidence that ectopic expression of Par-4 sensitizes
      Caki cells to TRAIL via modulation of multiple targets, including DR5, Bcl-2,
      Akt, and NF-kappaB.

PMID- 20127710
TI  - RECK-mediated inhibition of glioma migration and invasion.
AB  - RECK is an anti-tumoral gene whose activity has been associated with its
      inhibitory effects regulating MMP-2, MMP-9, and MT1-MMP. RECK level decreases as
      gliobastoma progresses, varying from less invasive grade II gliomas to very
      invasive human glioblastoma multiforme (GBM). Since RECK expression and glioma
      invasiveness show an inverse correlation, the aim of the present study is to
      investigate whether RECK expression would inhibit glioma invasive behavior. We
      conducted this study to explore forced RECK expression in the highly invasive
      T98G human GBM cell line. Expression levels as well as protein levels of RECK,
      MMP-2, MMP-9, and MT1-MMP were assessed by qPCR and immunoblotting in T98G/RECK+
      cells. The invasion and migration capacity of RECK+ cells was inhibited in
      transwell and wound assays. Dramatic cytoskeleton modifications were observed in
      the T98G/RECK+ cells, when compared to control cells, such as the abundance of
      stress fibers (contractile actin-myosin II bundles) and alteration of
      lamellipodia. T98G/RECK+ cells also displayed phosphorylated focal adhesion
      kinase (P-FAK) in mature focal adhesions associated with stress fibers; whereas P
      FAK in control cells was mostly associated with immature focal complexes.
      Interestingly, the RECK protein was predominantly localized at the leading edge
      of migrating cells, associated with membrane ruffles. Unexpectedly, introduced
      expression of RECK effectively inhibited the invasive process through
      rearrangement of actin filaments, promoting a decrease in migratory ability. This
      work has associated RECK tumor-suppressing activity with the inhibition of
      motility and invasion in this GBM model, which are two glioma characteristics
      responsible for the inefficiency of current available treatments.

PMID- 20127711
TI  - Initiation of telomere-mediated chromosomal rearrangements in cancer.
AB  - Telomeres are the ends of chromosomes and protect them from degradation and
      fusion. As such, their stability is required for normal cellular function.
      Telomere dysfunction is found often at the origin of cellular transformation and
      contributes to the onset of genomic instability, a hallmark of cancer cells. In
      this article, I discuss current data and concepts on telomere-mediated
      chromosomal rearrangements in cancer.

PMID- 20127712
TI  - Breviscapine protects against cardiac hypertrophy through blocking PKC-alpha
      dependent signaling.
AB  - Breviscapine is a mixture of flavonoid glycosides extracted from the Chinese
      herbs. Previous studies have shown that breviscapine possesses comprehensive
      pharmacological functions. However, very little is known about whether
      breviscapine have protective role on cardiac hypertrophy. The aim of the present
      study was to determine whether breviscapine attenuates cardiac hypertrophy
      induced by angiotensin II (Ang II) in cultured neonatal rat cardiac myocytes in
      vitro and pressure-overload-induced cardiac hypertrophy in mice in vivo. Our data
      demonstrated that breviscapine (2.5-15 microM) dose-dependently blocked cardiac
      hypertrophy induced by Ang II (1 microM) in vitro. The results further revealed
      that breviscapine (50 mg/kg/day) prevented cardiac hypertrophy induced by aortic
      banding as assessed by heart weight/body weight and lung weight/body weight
      ratios, echocardiographic parameters, and gene expression of hypertrophic
      markers. The inhibitory effect of breviscapine on cardiac hypertrophy is mediated
      by disrupting PKC-alpha-dependent ERK1/2 and PI3K/AKT signaling. Further studies
      showed that breviscapine inhibited inflammation by blocking NF-kappaB signaling,
      and attenuated fibrosis and collagen synthesis through abrogating Smad2/3
      signaling. Therefore, these findings indicate that breviscapine, which is a
      potentially safe and inexpensive therapy for clinical use, has protective
      potential in targeting cardiac hypertrophy and fibrosis through suppression of
      PKC-alpha-dependent signaling.

PMID- 20127713
TI  - Inhibition of glycogen synthase kinase-3beta promotes nuclear export of the
      androgen receptor through a CRM1-dependent mechanism in prostate cancer cell
      lines.
AB  - The androgen receptor (AR) is a ligand-dependent transcription factor belonging
      to the steroid hormone receptor superfamily. Under normal conditions, in the
      absence of a ligand, the AR is localized to the cytoplasm and is actively
      transported into the nucleus upon binding of androgens. In advanced prostate
      cancer (PCa) cell lines, an increased sensitivity to dihydrotestosterone (DHT),
      enabling the cells to proliferate under sub-physiological levels of androgens,
      has been associated with increased stability and nuclear localization of the AR.
      There is experimental evidence that the glycogen synthase kinase-3beta (GSK
      3beta), a multifunctional serine/threonine kinase is involved in estrogen and AR
      stability. As demonstrated in the following study by immunoprecipitation
      analysis, GSK-3beta binds to the AR forming complexes in the cytoplasm and in the
      nucleus. Furthermore, inhibition of GSK-3beta activity by pharmacological
      inhibitors like the maleimide SB216761, the chloromethyl-thienyl-ketone GSK-3
      inhibitor VI or the aminopyrazol GSK-3 inhibitor XIII in cells grown in the
      presence of DHT triggered a rapid nuclear export of endogenous AR as well as of
      green fluorescent AR-EosFP. The nuclear export of AR following GSK-3beta
      inhibition could be blocked by leptomycin B suggesting a CRM1-dependent export
      mechanism. This assumption is supported by the localization of a putative CRM1
      binding site at the C-terminus of the AR protein. The results suggest that GSK
      3beta is an important element not only in AR stability but also significantly
      alters nuclear translocation of the AR, thereby modulating the androgenic
      response of human PCa cells.

PMID- 20127714
TI  - Promiscuity of translocation partners in multiple myeloma.
AB  - Multiple myeloma (MM) is characterized by karyotypic instability, including
      chromosomal translocations involving the IGH locus. MM cells display a
      promiscuity of translocation partners, only some of which are recurrent. We
      propose that several factors, including temporal and spatial nuclear positioning
      of potential partner loci, "off-target" IGH diversification mechanisms, and
      aberrant repair pathways contribute to the promiscuity of translocation partners
      in MM. We speculate that in MM, IGH diversification processes [V(D)J
      recombination, somatic hypermutation, and class switch recombination] in B cells
      may not be restricted to specific stages of B-cell development or within specific
      immune tissues, but may occur in different temporal "windows." Before or during
      MM evolution, off-target activities of the enzymes involved in IGH modification
      processes may contribute to the generation of double-strand breaks (DSB) in
      translocation partner loci. In the parent B cells from which MM originates,
      spatial proximity within the nucleus of IGH and potential translocation partners
      contributes to the selection of a translocation partner and the clinical
      frequency at which a specific translocation occurs. The spatial proximity of IGH
      and specific translocation partners may be temporal and contribute not only to
      partner selection but also to the promiscuity of partners seen in MM. Lastly,
      aberrant repair mechanisms in MM progenitors (including the possibility that a Ku
      86 variant allows for positional instability at DSBs) may also contribute to the
      promiscuity of chromosome translocation partners in MM.

PMID- 20127715
TI  - A GPU solvent-solvent interaction calculation accelerator for biomolecular
      simulations using the GROMOS software.
AB  - During the past few years, graphics processing units (GPUs) have become extremely
      popular in the high performance computing community. In this study, we present an
      implementation of an acceleration engine for the solvent-solvent interaction
      evaluation of molecular dynamics simulations. By careful optimization of the
      algorithm speed-ups up to a factor of 54 (single-precision GPU vs. double
      precision CPU) could be achieved. The accuracy of the single-precision GPU
      implementation is carefully investigated and does not influence structural,
      thermodynamic, and dynamic quantities. Therefore, the implementation enables
      users of the GROMOS software for biomolecular simulation to run the solvent
      solvent interaction evaluation on a GPU, and thus, to speed-up their simulations
      by a factor 6-9.

PMID- 20127716
TI  - A massively multicore parallelization of the Kohn-Sham energy gradients.
AB  - In a previous article [Brown et al., J Chem Theory Comput 2009, 4, 1620], we
      described a quadrature-based formulation of the Kohn-Sham Coulomb problem that
      allows for efficient parallelization over thousands of small processor cores.
      Here, we present the analytic gradients of this modified Kohn-Sham scheme, and
      describe the parallel implementation of the gradients on a numerical accelerator
      architecture. We demonstrate an order-of-magnitude acceleration for the combined
      energy and gradient calculation over a conventional single-core implementation.

PMID- 20127717
TI  - Dynamic and structural scalings of the complexation between pDNA and bPEI in
      semidilute and low-salt solutions.
AB  - Using a combination of static and dynamic laser light scattering, we investigated
      the complexation of a supercoiled plasmid DNA (pDNA, 10(4) bp) and a branched
      polyethyleneimine (bPEI, M(w) = 25 kD) in semidilute and low-salt aqueous
      solutions. Our results unearth some scaling laws for dynamic and structural
      properties of the resultant complexes (polyplexes) with different bPEI:pDNA (N:P)
      molar ratios. Namely, the average scattering intensity (<I>) and the average
      linewidth of the Rayleigh peak (<Gamma>) are scaled to the scattering vector (q)
      as <I> proportional, variant q(alpha(s) ) or <Gamma> proportional, variant
      q(alpha(D) ), where alpha(S) and alpha(D) are two N:P dependent scaling
      exponents. The N:P ratio strongly affects the complexation. When N:P < 2.0, the
      motions of the negatively charged and extended pDNA chains and the polyplexes are
      highly correlated so that they behave like a transient network with a fractal
      dimension. As the N:P ratio increases, nearly all of pDNA chains condensed and
      the overall charge of the polyplexes reverses to slightly positive, resulting in
      a turbid dispersion of large loose aggregates made of smaller, but more compact,
      polyplexes. Further increase of N:P finally disrupts large loose aggregates,
      leading to a homogeneous transparent dispersion of the polyplexes.

PMID- 20127718
TI  - Profile of toll-like receptor-positive cells in septic and aseptic loosening of
      total hip arthroplasty implants.
AB  - Distinction between the two major complications of total hip replacement surgery,
      septic bacterial culture-positive and aseptic bacterial culture-negative
      osteolysis and loosening, is difficult due to the eventual role of bacterial
      remnants and biofilms, which are recognized by cells provided by toll-like
      receptors (TLRs) of the innate immune system. It was hypothesized that cell
      typing and TLR mapping might provide new information on the pathomechanisms of
      loosening. To test this hypothesis, septic (n = 10) and aseptic (n = 5) interface
      tissue as well as mildly inflamed osteoarthritic synovial membrane (n = 5)
      samples were characterized and compared using antibodies against several cell
      line-specific markers, including fibroblast, monocyte/macrophage, T cell, B cell,
      plasma cell and neutrophil markers, and TLRs. In osteoarthritic synovium, TLR
      positive cells were restricted to surface tissues and only few inflammatory cells
      were detected, whereas aseptic interface was heavily infiltrated with
      monocyte/macrophages, which were also the major TLR-positive cell type rendering
      the tissue reactive to TLR ligands. Interestingly, septic cases contained also
      neutrophil and lymphocyte infiltrates of which especially B-cell infiltrates
      might be clinically useful in discriminating the two major complications of the
      joint replacement surgery. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res,
      2010.

PMID- 20127719
TI  - Phosphoproteome reveals an atlas of protein signaling networks during osteoblast
      adhesion.
AB  - Cell adhesion on surfaces is a fundamental process in the emerging biomaterials
      field and developmental events as well. However, the mechanisms regulating this
      biological process in osteoblasts are not fully understood. Reversible
      phosphorylation catalyzed by kinases is probably the most important regulatory
      mechanism in eukaryotes. Therefore, the goal of this study is to assess
      osteoblast adhesion through a molecular prism under a peptide array technology,
      revealing essential signaling proteins governing adhesion-related events. First,
      we showed that there are main morphological changes on osteoblast shape during
      adhesion up to 3 h. Second, besides classical proteins activated upon integrin
      activation, our results showed a novel network involving signaling proteins such
      as Rap1A, PKA, PKC, and GSK3beta during osteoblast adhesion on polystyrene.
      Third, these proteins were grouped in different signaling cascades including
      focal adhesion establishment, cytoskeleton rearrangement, and cell-cycle arrest.
      We have thus provided evidence that a global phosphorylation screening is able to
      yield a systems-oriented look at osteoblast adhesion, providing new insights for
      understanding of bone formation and improvement of cell-substratum interactions.
      Altogether, these statements are necessary means for further intervention and
      development of new approaches for the progress of tissue engineering.

PMID- 20127720
TI  - Control of intestinal promoter activity of the cellular migratory regulator gene
      ELMO3 by CDX2 and SP1.
AB  - An important aspect of the cellular differentiation in the intestine is the
      migration of epithelial cells from the crypt to the villus tip. As homeodomaine
      transcription factor CDX2 has been suggested to influence cell migration, we
      performed a genome-wide promoter analysis for CDX2 binding in the differentiated
      human intestinal cancer cell line Caco-2 in order to identify CDX2-regulated
      genes involved in cellular migration. The engulfment and cell motility 3 (ELMO3)
      gene was identified as a potential CDX2 target gene. ELMO3 is an essential
      upstream regulator of the GTP-binding protein RAC during cell migration. However,
      no information is available about the transcriptional regulation of the ELMO3
      gene. The aim of this study was to investigate the potential role of CDX2 in the
      regulation of the ELMO3 promoter activity. Electrophoretic mobility shift assays
      showed that CDX2 bound to conserved CDX2 sequences and mutations of the CDX2
      binding sites, significantly reduced the promoter activity. Reporter gene assays
      demonstrated that the region mediating ELMO3 basal transcriptional activity to be
      located between -270 and -31 bp. Sequence analysis revealed no typical TATA-box,
      but four GC-rich sequences. In vitro analyses (electrophoretic mobility shift
      assays and promoter analyses) demonstrate that the SP1-binding sites are likely
      to play an important role in regulating the ELMO3 promoter activity. Furthermore,
      we showed here that CDX2 and SP1 can activate the ELMO3 promoter. Taken together,
      the present study reports the first characterization of the ELMO3 promoter and
      suggests a significant role of CDX2 in the basal transcriptional regulation of
      the intestine-specific expression of ELMO3, possibly through interaction with
      SP1.

PMID- 20127722
TI  - Intact T cell receptor signaling by CD4(+) T cells cultured in the rotating wall
      vessel bioreactor.
AB  - T lymphocytes fail to proliferate or secrete cytokines in response to T cell
      receptor (TCR) agonists during culture in spaceflight or ground-based
      microgravity analogs such as rotating wall-vessel (RWV) bioreactors. In RWVs,
      these responses can be rescued by co-stimulation with sub-mitogenic doses of the
      diacyl glycerol (DAG) mimetic phorbol myristate acetate. Based on this result we
      hypothesized that TCR activation is abrogated in the RWV due to impaired DAG
      signaling downstream of the TCR. To test this hypothesis we compared TCR-induced
      signal transduction by primary, human, CD4(+) T cells in RWV, and static culture.
      Surprisingly, we found little evidence of impaired DAG signaling in the RWV.
      Upstream of DAG, the tyrosine phosphorylation of several key components of the
      TCR-proximal signal was not affected by culture in the RWV. Similarly, the
      phosphorylation and compartmentalization of ERK and the degradation of IkappaB
      were unchanged by culture in the RWV indicating that RAS- and PKC-mediated
      signaling downstream of DAG are also unaffected by simulated microgravity. We
      conclude from these data that TCR signaling through DAG remains intact during
      culture in the RWV, and that the loss of functional T cell activation in this
      venue derives from the affect of simulated microgravity on cellular processes
      that are independent of the canonical TCR pathway.

PMID- 20127721
TI  - Alcohol and PRAS40 knockdown decrease mTOR activity and protein synthesis via
      AMPK signaling and changes in mTORC1 interaction.
AB  - The mTORC1 protein kinase complex consists of mTOR, raptor, mLST8/GbetaL and
      PRAS40. Previously, we reported that mTOR plays an important role in regulating
      protein synthesis in response to alcohol (EtOH). However, the mechanisms by which
      EtOH regulates mTORC1 activity have not been established. Here, we investigated
      the effect of EtOH on the phosphorylation and interaction of components of mTORC1
      in C2C12 myocytes. We also examined the specific role that PRAS40 plays in this
      process. Incubation of myocytes with EtOH (100 mM, 24 h) increased raptor and
      PRAS40 phosphorylation. Likewise, there were increased levels of the PRAS40
      upstream regulators Akt and IRS-1. EtOH also caused changes in mTORC1 protein
      protein interactions. EtOH enhanced the binding of raptor and PRAS40 with mTOR.
      These alterations occurred in concert with increased binding of 14-3-3 to raptor,
      while the PRAS40 and 14-3-3 interaction was not affected. The shRNA knockdown
      (KD) of PRAS40 decreased protein synthesis similarly to EtOH. PRAS40 KD increased
      raptor phosphorylation and its association with 14-3-3, whereas decreased GbetaL
      mTOR binding. The effects of EtOH and PRAS40 KD were mediated by AMPK. Both
      factors increased in vitro AMPK activity towards the substrate raptor. In
      addition, KD enhanced the activity of AMPK towards TSC2. Collectively, our
      results indicate that EtOH stabilizes the association of raptor, PRAS40, and
      GbetaL with mTOR, while likewise increasing the interaction of raptor with 14-3
      3. These data suggest a possible mechanism for the inhibitory effects of EtOH on
      mTOR kinase activity and protein synthesis in myocytes.

PMID- 20127723
TI  - In vitro activities of plant extracts from Saudi Arabia against malaria,
      leishmaniasis, sleeping sickness and Chagas disease.
AB  - The in vitro activity of the methanol extracts of 51 plants randomly collected
      from the Kingdom of Saudi Arabia and some of their fractions (petroleum ether,
      chloroform, ethyl acetate and aqueous) were evaluated against Plasmodium
      falciparum, Trypanosoma brucei brucei, T. cruzi and Leishmania infantum, as well
      as toxicity against MRC-5 fibroblast cells. Ten crude methanolic extracts that
      demonstrated potent and adequately selective antiprotozoal activity were
      subjected to solvent fractionation using petroleum ether, ethyl acetate and
      chloroform. Only three samples showed promising antiprotozoal activity. Argemone
      ochroleuca (CHCl(3) fraction) showed pronounced activity against P.
      falciparum(GHA) (IC(50) 0.32 microg/mL) and T. cruzi (IC(50) 0.30 microg/mL) with
      low cytotoxicity against MRC-5 cells (CC(50) 11.6 microg/mL). Capparis spinosa
      (EtOAc fraction) showed pronounced activity against P. falciparum(GHA) with an
      IC(50) 0.50 microg/mL in the absence of toxicity against MRC-5 cell line (CC(50)
      > 30 microg/mL). Heliotropium curassavicum (CHCl(3) fraction) showed similar
      activity against P. falciparum (IC(50) 0.65 microg/mL; MRC-5 CC(50) > 30 microg
      /mL). These three extracts will be subjected for further extensive studies to
      isolate and identify their active constituents.

PMID- 20127724
TI  - Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis
      as determined from synovial fluid cellular composition and gene expression.
AB  - OBJECTIVE: To identify biomarkers in the first synovial fluid (SF) aspirate
      obtained from children with oligoarticular juvenile idiopathic arthritis (JIA),
      which could be used to identify children whose disease is likely to extend to a
      more severe phenotype. METHODS: Patients with recent-onset oligoarticular JIA
      were identified and grouped according to those whose mild disease persisted
      (persistent disease) or those whose disease would extend from a mild to more
      severe phenotype (extended-to-be disease) at 1 year after diagnosis. Flow
      cytometry was used to delineate differences in the mononuclear cell populations
      between the first blood sample and first SF aspirate from the same patient and
      between outcome (persistent versus extended-to-be) groups. Proportions of
      lymphocytes in the joint were modeled on chemotaxis of lymphocytes to CCL5, using
      Transwell migration assays. Levels of CCL5 in the SF were quantified by enzyme
      linked immunosorbent assay. RNA profiles of SF mononuclear cells were compared
      between groups using the Affymetrix GeneChip hybridization protocol and
      hierarchical clustering analyses. RESULTS: Compared with peripheral blood
      mononuclear cells, SF mononuclear cells displayed an expansion of CD8+ T cells,
      reduced proportion of B cells, and expansion of CD16- natural killer cells. The
      lower CD4:CD8 ratio in the SF was recapitulated in vitro by the observed
      migration of blood T cells in response to CCL5. Synovial CCL5 levels were higher
      in children whose disease extended to a more severe phenotype. The CD4:CD8 ratio
      in the SF was significantly lower in patients with extended-to-be oligoarticular
      JIA (0.57 compared with 0.90 in the persistent disease group, difference 0.33,
      95% confidence interval 0.04-0.62; P = 0.009). Gene expression profiling revealed
      that 344 genes were >1.5-fold differentially expressed between outcome groups (P
      < 0.05), and these included genes associated with inflammation and macrophage
      differentiation, which showed increased levels in patients with extended disease
      at 1 year, and genes associated with immune regulation, which showed increased
      levels in patients with persistent disease at 1 year. CONCLUSION: Analyses of the
      proportions of synovial lymphocytes, levels of CCL5, and differential gene
      expression yielded potential biomarkers with which to predict the likelihood of
      extension of oligoarticular JIA to a more severe disease phenotype.

PMID- 20127725
TI  - Psychiatric diagnoses among Iraq and Afghanistan war veterans screened for
      deployment-related traumatic brain injury.
AB  - The authors examined psychiatric diagnoses in administrative records for 13,201
      United States military veterans who were screened for traumatic brain injury
      (TBI) in Department of Veterans Affairs facilities. Over 80% of the veterans with
      positive TBI screens had psychiatric diagnoses. Compared to veterans with
      negative TBI screens, those with positive screens, but without confirmed TBI
      status, were three times more likely to have a posttraumatic stress disorder
      (PTSD) diagnosis and were two times more likely to have depression and substance
      related diagnoses. Among veterans with positive TBI screens, those with
      clinically confirmed TBI status were more likely than those without confirmed TBI
      status to have diagnoses for PTSD, anxiety, and adjustment disorders. These
      findings have implications for health care delivery and provider education.

PMID- 20127726
TI  - Posttraumatic stress disorder symptoms and functional impairment among OEF and
      OIF National Guard and Reserve veterans.
AB  - The aims of the present investigation were (a) to examine associations between
      posttraumatic stress disorder (PTSD; diagnosis and symptoms) and different
      aspects of functioning, severity, and subjective distress among Operation Iraqi
      Freedom and Operation Enduring Freedom National Guard and Reserve veterans, and
      (b) to examine the unique contribution of PTSD symptom clusters to different
      aspects of functioning and distress. Participants were 124 veterans who had
      returned from war-zone deployment. A PTSD diagnosis and PTSD symptoms were
      significantly associated with nearly all of the psychosocial functioning and
      distress measures, controlling for Axis I disorders and other covariates. Of the
      PTSD symptom clusters, numbing/avoidance symptoms were the strongest predictors
      of interpersonal and social functioning, and hyperarousal symptoms were the
      strongest predictors of overall severity and distress.

PMID- 20127728
TI  - The effect on energy expenditure of walking on gradients or carrying burdens.
AB  - The effectiveness of people walking while carrying burdens and/or on gradients
      has been of interest to anthropologists for some time. No empirical equation
      exists, however, to assess the energetic expenditure of individuals traveling
      downhill with burdens and whether or not all people increase their energetic
      expenditure over unburdened level travel when carrying relatively light burdens
      (<20% of body mass) remains unclear. To begin to rectify this lacunae, gait
      parameters, physiological variables, and the energetic expenditure of 11 adults
      were assessed as they walked with burdens of 5 and 10 kg on a level treadmill and
      while they walked unburdened on gradients +/-8 and +/-16%. These data were then
      compared to predictive equations and data available from the literature. Velocity
      and body mass were combined with gradient and burden mass, where appropriate, as
      independent covariates to create predictive equations, which explained >80% of
      the variation in energetic expenditure. These new equations are appropriate for
      predicting energetic expenditure in people carrying burdens of <20% of total body
      mass or walking up and downhill at gradients of <20%.

PMID- 20127729
TI  - Proceedings of the Human Biology Association 34th Annual Meeting, Sheraton Hotel
      and Towers, Chicago, IL.

PMID- 20127731
TI  - Mapping pro- and antiangiogenic factors on the surface of prostasomes of normal
      and malignant cell origin.
AB  - BACKGROUND: Angiogenesis is the formation of new blood vessels by capillary
      sprouting from pre-existing vessels. Tumor growth is angiogenesis-dependent and
      the formation of new blood vessels is associated with the increased expression of
      angiogenic factors. Prostasomes are secretory granules produced, stored and
      released by the glandular epithelial cells of the prostate. We investigated the
      expression of selected angiogenic and anti-angiogenic factors on the surface of
      prostasomes of different origins as well as the direct effect of prostasomes on
      angiogenesis. METHODS: VEGF, endothelin-1, endostatin, and thrombospondin-1 were
      determined on prostasomes from seminal fluid and human prostate cancer cell lines
      (DU145,PC-3,LNCaP) using different immunochemical techniques. Human dermal
      microvascular endothelial cells were incubated with seminal and DU145 cell
      prostasomes and with radioactive thymidine. The effect of prostasomes on
      angiogenesis was judged by measuring the uptake of labeled thymidine. The
      presence of any deleterious effects of prostasomes on the endothelial cells was
      investigated using thymidine assay and confocal laser microscopy. RESULTS: VEGF
      and endothelin-1 were determined on malignant cell-prostasomes (no difference
      between cell lines) but not determined on seminal prostasomes. The same applies
      for the expression of endostatin but with much higher expression on malignant
      cell-prostasomes with obvious differences between them. Seminal and DU145 cell
      prostasomes were found to have anti-angiogenic effect which was more expressed by
      DU145 cell-prostasomes. No deleterious effect of prostasomes on endothelial
      function was detected using either thymidine assay or microscopy. CONCLUSIONS:
      Prostasomes contain pro- and anti-angiogenic factors that function to counteract
      each other unless the impact from one side exceeds the other to bring about
      dysequilibrium.

PMID- 20127732
TI  - A study of high-dose oral silybin-phytosome followed by prostatectomy in patients
      with localized prostate cancer.
AB  - BACKGROUND: Silibinin is a polyphenolic flavonolignan derived from milk thistle
      (Silybum marianium) with anti-oxidant properties. The purpose of the current
      trial was to determine the tissue and blood effects of high-dose silybin
      phytosome in prostate cancer patients. METHODS: Subjects with localized prostate
      cancer planning for a prostatectomy were eligible to enroll. Six patients
      received 13 g of silybin-phytosome daily with six additional participants serving
      as control subjects. RESULTS: Patients in the treatment arm received silybin
      phytosome for 14-31 days (mean was 20 days) prior to surgery. Silibinin blood
      levels were measured 1 hr after the first silybin-phytosome dose with a mean
      value of 19.7 microM. Trough silibinin levels were assessed at the end of the
      trial with an average concentration of 1.2 microM. In contrast to the high peak
      levels of silibinin observed in blood, the highest silibinin level observed in
      the harvested prostate tissue was 496.6 pmol/g. There were no significant
      differences noted in baseline and post-treatment blood levels of IGF-I and IGFBP
      3. One of the treated patients developed a grade 4 post-operative thromboembolic
      event. The other observed toxicities in the treatment group were mild: four
      subjects had diarrhea and one had asymptomatic grade 2 hyperbilirubinemia which
      was transient. CONCLUSIONS: High-dose oral silybin-phytosome achieves high blood
      concentrations transiently, but low levels of silibinin are seen in prostate
      tissue. Silibinin's lack of tissue penetration may be explained by its short half
      life, the brief duration of therapy in this study or an active process removing
      silibinin from the prostate.

PMID- 20127733
TI  - Fibronectin confers survival against chemotherapeutic agents but not against
      radiotherapy in DU145 prostate cancer cells: involvement of the insulin like
      growth factor-1 receptor.
AB  - BACKGROUND: Tumor growth is influenced by an increase in cell proliferation and a
      reduction in apoptosis; both of which are affected by alterations in
      extracellular matrix (ECM). Our aim was to assess if the susceptibility of
      prostate cancer cells to apoptosis induced by either chemotherapeutics or
      radiotherapy was altered by changes in the ECM. METHODS: Prostate cancer cell
      lines LNCaP and DU145 (androgen independent) cells were treated with
      chemotherapeutics (ceramide and docetaxel) or radiotherapy in the presence or
      absence of fibronectin, laminin, or vitronectin. Cell death was assessed using
      Trypan blue cell counting and apoptosis was confirmed by measuring PARP cleavage
      by Western immunoblotting (WIB). To identify a mechanism of action, changes in
      the abundance (WIB) or association (immunoprecipitation followed by WIB) of key
      proteins was also assessed. RESULTS: We found that fibronectin, but not laminin
      or vitronectin activated a survival pathway that protected DU145 but not LNCaP
      prostate cancer cells against ceramide and docetaxel-induced apoptosis but not
      that induced by radiotherapy. This survival effect involved the insulin-like
      growth factor (IGF-I) and beta1 integrin receptors and was associated with an
      increase in the recruitment of the beta1 integrin to a complex containing the IGF
      IR and protein receptor for activated C kinase (RACK-1) and an increase in the
      abundance of a MAPK-phosphatase-1 (MKP-1). CONCLUSIONS: Changes in the ECM
      associated with disease progression may contribute to resistance to
      chemotherapeutic drugs but not to radiation therapy. The susceptibility to
      chemotherapy may be improved by targeting either the IGF-I or beta1 integrin
      receptors.

PMID- 20127734
TI  - Regulation of androgen receptor transactivity and mTOR-S6 kinase pathway by Rheb
      in prostate cancer cell proliferation.
AB  - BACKGROUND: Ras homolog-enriched in brain (Rheb), a small GTP-binding protein, is
      associated with prostate carcinogenesis through activating mammalian target of
      rapamycin (mTOR) signaling pathway. This study aimed to elucidate whether Rheb
      promotes proliferation of prostate cancer cells and can act as a potent
      therapeutic target in prostate cancer. METHODS: Prostate cancer cell lines and
      human prostatic tissues were examined for the expression of Rheb. The effects of
      forced expression or knockdown of Rheb on cell proliferation were also examined.
      Semi-quantitative and quantitative RT-PCR were performed to evaluate mRNA
      expression. Western blotting was used to examine protein expression. Cell count
      and WST-1 assay were used to measure cell proliferation. Fluorescence-activated
      cell sorting was used to assess the cell cycle. RESULTS: Rheb mRNA and protein
      expression was higher in more aggressive, androgen-independent prostate cancer
      cell lines PC3, DU145, and C4-2, compared with the less aggressive LNCaP. Rheb
      expression was higher in cancer tissues than in benign prostatic epithelia.
      Forced expression of Rheb in LNCaP cells accelerated proliferation without
      enhancing androgen receptor transactivity. Attenuation of Rheb expression or
      treatment with the mTOR inhibitor rapamycin decreased proliferation of PC3 and
      DU145 cells, with a decrease in the activated form of p70S6 kinase, one of the
      main targets of mTOR. CONCLUSIONS: Rheb potentiates proliferation of prostate
      cancer cells and inhibition of Rheb or mTOR can lead to suppressed proliferation
      of aggressive prostate cancer cell lines in vitro. Rheb and the mTOR pathway are
      therefore probable targets for suppressing prostate cancer.

PMID- 20127735
TI  - Evaluation of the frequency of putative prostate cancer stem cells in primary and
      metastatic prostate cancer.
AB  - BACKGROUND: Tumour cells with a stem cell-like phenotype have recently been
      identified in prostate tumors and it has been suggested that this population may
      be responsible for the diversity of cell types within tumors and also for the
      initiation of metastases. These cells carry a number of defined markers: they are
      cd133 and cd44+ve and express high levels of alpha2beta1 integrin. In this study
      we have, for the first time, assessed matched primary and bone marrow biopsies
      from prostate cancer patients for the distribution of cells carrying these and a
      number of other putative stem cell markers. METHODS: Eleven matched (primary and
      bone metastasis) specimens from prostate cancer patients were assessed for the
      presence of cd133, cd44, alpha2beta1 integrin, CXCR4, c-met, alpha6 integrin, and
      nestin using immunohistochemistry and stain intensity and distribution scored.
      RESULTS: In the bone metastases, tumor cells staining positively for cd133 were
      detected at low frequency in approximately 50% of samples. Staining for nestin
      was confined to endothelium. Positive staining of tumor cells for the other
      antigens was present at variable frequency in >70% of metastases with the
      exception of CXCR4 which was absent from all but 2 specimens. Where positive
      staining of tumor cells was present in the metastasis, cells staining for each
      antigen were present in the matched primary with the exception of cd44 which was
      absent in all but 2/11 matched primary tissues. CONCLUSIONS: In established
      metastases no single or combination of marker expression profiles identify the
      established metastatic phenotype, although cd44 expression was shown to be more
      frequent in metastases that in primary cancers.

PMID- 20127736
TI  - Genetic alterations and changes in expression of histone demethylases in prostate
      cancer.
AB  - BACKGROUND: Histone demethylases LSD1, JHDM2A, and GASC1 have been suggested to
      function as androgen receptor co-activators, and to be involved in prostate
      cancer (PC) progression. We aim to identify genetic alterations and changes in
      expression of these genes in PC. METHODS: PC cell lines, xenografts as well as
      clinical specimens were screened for mutations using denaturating high
      performance liquid chromatography and sequencing, and for expression alterations
      by using quantitative RT-PCR and immunohistochemistry. RESULTS: Only known single
      nucleotide polymorphisms, but no mutations, were found in these genes. JHDMA2
      mRNA expression was slightly increased (P < 0.05) in PC compared with benign
      prostate hyperplasia (BPH), whereas the expression of GASC1 was slightly higher
      (P < 0.05) in castration-resistant PC (CRPC) compared with untreated PC or BPH.
      The mRNA expression of LSD1 was not altered in PC. The expression of LSD1 protein
      was somewhat, although not statistically significantly (P = 0.0521) lower in CRPC
      compared with untreated PC. In prostatectomy specimens, the level of LSD1 protein
      expression was associated with low pT-stage (P = 0.0402), but not with Gleason
      score or progression-free survival. CONCLUSIONS: As no genetic alterations and
      only very modest expression changes were found, it is unlikely that LSD1, JHDM2A,
      or GASC1 play a major role in the progression of PC.

PMID- 20127737
TI  - Effect of bendiocarb on development of the chick embryo.
AB  - Agrochemicals, including pesticides, are being used in increasing amounts in
      agriculture and are therefore potential environmental contaminants which may
      affect a variety of biological systems. The pesticide residues directly affect
      the embryos, disturbing their normal development and causing pathophysiological
      and morphological changes. We have observed embryotoxicity of cholinesterase
      inhibitor bendiocarb in the chick embryo. The pesticide dissolved in 10% acetone
      in water for injection was applied in a volume of 200 microl over the embryo
      through membrana papyracea at embryonic days (ED) 2, 3, 4, 5 and 10. The toxicity
      of bendiocarb was rather low, and lethal dose (LD(50)) decreased with advancing
      development from 0.97 mg per egg at ED 2 to 28.6 mg on ED 5. The malformations in
      surviving embryos were observed rarely (<2%) and occurred in both control and
      experimental groups. In the treatment at ED 5 and 10 there was a statistically
      significant reduction in body weight, but the maximum difference from controls
      was below 14%. In treated chick embryos on ED 3 and 4 was observed a small but
      not significant increase in number of dead cells using supravital staining. We
      conclude that bendiocarb possesses no significant toxicity in the avian embryo.
      Our analysis of bendiocarb embryotoxic potential in the chick embryo supports the
      earlier observations in other animal models, testifying to the relative safety of
      bendiocarb for the embryo or fetus.

PMID- 20127738
TI  - Time-dependent density functional theory study on the hydrogen bonding-induced
      twisted intramolecular charge-transfer excited states of 2-(4'-N,N
      dimethylaminophenyl)imidazo[4,5-b]pyridine.
AB  - In this work, the time-dependent density functional theory (TDDFT) method was
      carried out to investigate the hydrogen-bonded intramolecular charge-transfer
      excited state of 2-(4'-N,N-dimethylaminophenyl)imidazo[4,5-b]pyridine (DMAPIP) in
      methanol (MeOH) solvent. All the geometric conformations of the ground state and
      locally excited (LE) state and the twisted intramolecular charge-transfer (TICT)
      state for isolated DMAPIP and its hydrogen-bonded complexes have been optimized.
      At the same time, the absorption and fluorescence spectra of DMAPIP and the
      hydrogen-bonded complexes in different electronic states are also calculated. We
      theoretically demonstrated for the first time that the intermolecular hydrogen
      bond formed between DMAPIP and MeOH can induce the formation of the TICT state
      for DMAPIP in MeOH solvent. Therefore, the two components at 414 and 506 nm
      observed in the fluorescence spectra of DMAPIP in MeOH solvent were reassigned in
      this work. The fluorescence peak at 414 nm is confirmed to be the LE state.
      Furthermore, the red-shifted shoulder at 506 nm should be originated from the
      hydrogen-bonded TICT excited state.

PMID- 20127739
TI  - Investigation of excited-state properties of fluorene-thiophene oligomers by the
      SAC-CI theoretical approach.
AB  - Excited states of fluorene-ethylenedioxythiophene (FEDOT) and fluorene-S,S
      dioxide-thiophene (FTSO2) monomers and dimers were studied by the symmetry
      adapted cluster (SAC)-configuration interaction (CI) method. The absorption and
      emission peaks observed in the experimental spectra were theoretically assigned.
      The first three excited states of the optimized conformers, and the conformers of
      several torsional angles, were computed by SAC-CI/D95(d). Accurate absorption
      spectra were simulated by taking the thermal average for the conformers of
      torsional angles from 0 degrees to 90 degrees. The conformers of torsional angles
      0 degrees, 15 degrees, and 30 degrees mainly contributed to the absorption
      spectra. The full width at half-maximum of the FEDOT absorption band is 0.60 eV
      (4839 cm(-1)), which agrees very well with the experimental value of 0.61 eV
      (4900 cm(-1)). The maximum absorption wavelength is located at 303 nm, which is
      close to those of the experimental band (327 nm). The calculated absorption
      spectrum of FTSO2 showed two bands in the range of 225-450 nm. This agrees very
      well with the available experimental spectrum of a polymer of FTSO2, where two
      bands are detected. The excited-state geometries were investigated by CIS/6
      31G(d). These showed a quinoid-type structure which exhibited a shortening of the
      inter-ring distance (0.06 A for FEDOT and 0.04 A for FTSO2). The calculated
      emission energy of FEDOT is 3.43 eV, which agrees very well with the available
      experimental data (3.46 eV). The fwhm(E) is about 0.49 eV (3952 cm(-1)), while
      the experimental fwhm is 0.43 eV (3500 cm(-1)). For FTSO2, two bands were also
      found in the emission spectrum.

PMID- 20127740
TI  - Improving the accuracy of predicting disulfide connectivity by feature selection.
AB  - Disulfide bonds are primary covalent cross-links formed between two cysteine
      residues in the same or different protein polypeptide chains, which play
      important roles in the folding and stability of proteins. However, computational
      prediction of disulfide connectivity directly from protein primary sequences is
      challenging due to the nonlocal nature of disulfide bonds in the context of
      sequences, and the number of possible disulfide patterns grows exponentially when
      the number of cysteine residues increases. In the previous studies, disulfide
      connectivity prediction was usually performed in high-dimensional feature space,
      which can cause a variety of problems in statistical learning, such as the
      dimension disaster, overfitting, and feature redundancy. In this study, we
      propose an efficient feature selection technique for analyzing the importance of
      each feature component. On the basis of this approach, we selected the most
      important features for predicting the connectivity pattern of intra-chain
      disulfide bonds. Our results have shown that the high-dimensional features
      contain redundant information, and the prediction performance can be further
      improved when these high-dimensional features are reduced to a lower but more
      compact dimensional space. Our results also indicate that the global protein
      features contribute little to the formation and prediction of disulfide bonds,
      while the local sequential and structural information play important roles. All
      these findings provide important insights for structural studies of disulfide
      rich proteins.

PMID- 20127741
TI  - Evaluation of the performance of four molecular docking programs on a diverse set
      of protein-ligand complexes.
AB  - Many molecular docking programs are available nowadays, and thus it is of great
      practical value to evaluate and compare their performance. We have conducted an
      extensive evaluation of four popular commercial molecular docking programs,
      including Glide, GOLD, LigandFit, and Surflex. Our test set consists of 195
      protein-ligand complexes with high-resolution crystal structures (resolution
      <or=2.5 A) and reliable binding data [dissociation constant (K(d)) or inhibition
      constant (K(i))], which are selected from the PDBbind database with an emphasis
      on diversity. The top-ranked solutions produced by these programs are compared to
      the native ligand binding poses observed in crystal structures. Glide and GOLD
      demonstrate better accuracy than the other two on the entire test set. Their
      results are also less sensitive to the starting structures for docking.
      Comparison of the results produced by these programs at three different
      computation levels reveal that their accuracy are not always proportional to CPU
      cost as one may expect. The binding scores of the top-ranked solutions produced
      by these programs are in low to moderate correlations with experimentally
      measured binding data. Further analyses on the outcomes of these programs on
      three suites of subsets of protein-ligand complexes indicate that these programs
      are less capable to handle really flexible ligands and relatively flat binding
      sites, and they have different preferences to hydrophilic/hydrophobic binding
      sites. Our evaluation can help other researchers to make reasonable choices among
      available molecular docking programs. It is also valuable for program developers
      to improve their methods further.

PMID- 20127742
TI  - 27 ps DFT molecular dynamics simulation of alpha-maltose: A reduced basis set
      study.
AB  - DFT molecular dynamics simulations are time intensive when carried out on
      carbohydrates such as alpha-maltose. In a recent publication (Momany et al., J.
      Mol. Struct. THEOCHEM, submitted) forces for dynamics were generated from B3LYP/6
      31+G* electronic structure calculations. The implicit solvent method COSMO was
      applied to simulate the solution environment. Here we present a modification of
      the DFT method that keeps the critical aspects of the larger basis set (B3LYP/6
      31+G*) while allowing the less-essential atom interactions to be calculated using
      a smaller basis set, thus allowing for faster completion without sacrificing the
      interactions dictating the hydrogen bonding networks in alpha-maltose. In
      previous studies, the gg'-gg-c solvated form quickly converged to the "r" form
      during a 5 ps dynamics run. This important conformational transition is tested by
      carrying out a long 27 ps simulation. The trend for the "r" conformer to be most
      stable during dynamics when fully solvated, is confirmed, resulting in
      approximately 20/80% c/r population. Further, the study shows that considerable
      molecular end effects are important, the reducing end being fairly stable, the O6
      H pointing at the O5, while the nonreducing end moves freely to take on different
      conformations. Some "kink" and transition state forms are populated during the
      simulation. The average H1'...H4 distance of 2.28 A confirms that the syn form is
      the primary glycosidic conformation, while the average C1'-O1'-C4 bond angle was
      118.8 degrees , in excellent agreement with experimental values. The length of
      this simulation allowed the evaluation of vibrational frequencies by Fourier
      transform of the velocity correlation function, taken from different time
      segments along the simulation path.

PMID- 20127744
TI  - Thermodynamic stability of hydrogen-bonded systems in polar and nonpolar
      environments.
AB  - The thermodynamic properties of a selected set of benchmark hydrogen-bonded
      systems (acetic acid dimer and the complexes of acetic acid with acetamide and
      methanol) was studied with the goal of obtaining detailed information on solvent
      effects on the hydrogen-bonded interactions using water, chloroform, and n
      heptane as representatives for a wide range in the dielectric constant. Solvent
      effects were investigated using both explicit and implicit solvation models. For
      the explicit description of the solvent, molecular dynamics and Monte Carlo
      simulations in the isothermal-isobaric (NpT) ensemble combined with the free
      energy perturbation technique were performed to determine solvation free
      energies. Within the implicit solvation approach, the polarizable continuum model
      and the conductor-like screening model were applied. Combination of gas phase
      results with the results obtained from the different solvation models through an
      appropriate thermodynamic cycle allows estimation of complexation free energies,
      enthalpies, and the respective entropic contributions in solution. Owing to the
      strong solvation effects of water the cyclic acetic acid dimer is not stable in
      aqueous solution. In less polar solvents the double hydrogen bond structure of
      the acetic acid dimer remains stable. This finding is in agreement with previous
      theoretical and experimental results. A similar trend as for the acetic acid
      dimer is also observed for the acetamide complex. The methanol complex was found
      to be thermodynamically unstable in gas phase as well as in any of the three
      solvents.

PMID- 20127745
TI  - Global minimum geometries of acetylene clusters (HCCH)n with n < or = 55 obtained
      by a heuristic method combined with geometrical perturbations.
AB  - Geometry optimization of acetylene clusters (HCCH)(n) in the range of n < or = 55
      was carried out with a recently proposed intermolecular potential consisting of
      Morse potentials, damped dispersion terms, and damped Coulomb terms. The
      heuristic method developed by the present author was used in the optimization:
      optimal geometries were searched by using geometry perturbations and subsequent
      local optimizations. The calculations were repeated until the global minimum was
      found for each cluster at least three times. The obtained results were analyzed
      to examine structural evolution of the clusters. The geometries of the clusters
      with n > or = 25 were similar to the geometry in the cubic crystal of acetylene
      whereas smaller clusters take icosahedron-based geometries.

PMID- 20127746
TI  - Determinants of general practitioners' wages in England.
AB  - We analyse the determinants of annual net income and wages (net income/hours) of
      general practitioners (GPs) using data for 2271 GPs in England recorded during
      Autumn 2008. The average GP had an annual net income of L97,500 and worked 43 h
      per week. The mean wage was L51 per h. Net income and wages depended on gender,
      experience, list size, partnership size, whether or not the GP worked in a
      dispensing practice, whether they were salaried of self-employed, whether they
      worked in a practice with a nationally or locally negotiated contract, and the
      characteristics of the local population (proportion from ethnic minorities,
      rurality, and income deprivation). The findings have implications for pay
      discrimination by GP gender and ethnicity, GP preferences for partnership size,
      incentives for competition for patients, and compensating differentials for local
      population characteristics. They also shed light on the attractiveness to GPs in
      England of locally negotiated (personal medical services) versus nationally
      negotiated (general medical services) contracts.

PMID- 20127747
TI  - A comparison of positive and negative ion collision-induced dissociation for
      model heptapeptides with one basic residue.
AB  - The effects of the identity and position of basic residues on peptide
      dissociation were explored in the positive and negative modes. Low-energy
      collision-induced dissociation (CID) was performed on singly protonated and
      deprotonated heptapeptides of the type: XAAAAAA, AAAXAAA, AAAAAXA and AAAAAAX,
      where X is arginine (R), lysine (K) or histidine (H) residues and A is alanine.
      For [M + H](+), the CID spectra are dominated by cleavages adjacent to the basic
      residues and the majority of the product ions contain the basic residues. The
      order of a basic residue's influence on fragmentation of [M + H](+) is arginine >
      histidine approximately lysine, which is also the order of decreasing gas-phase
      basicity for these amino acids. These results are consistent with the side chains
      of basic residues being positive ion charge sites and with the more basic
      arginine residues having a higher retention (i.e. sequestering) of the positive
      charge. In contrast, for [M-H](-) the identity and position of basic residues has
      almost no effect on backbone fragmentation. This is consistent with basic
      residues not being negative mode charge sites. For these peptides, more complete
      series of backbone fragments, which are important in the sequencing of unknowns,
      can be found in the negative mode. Spectra at both polarities contain C-terminal
      y-ions, but y(n)''(+) has two more hydrogens than the corresponding y(n)(-).
      Another major difference is the production of the N-terminal backbone series
      b(n)(+) in the positive mode and c(n)(-) in the negative mode. Thus, comparison
      of positive and negative ion spectra with an emphasis on searching for pairs of
      ions that differ by 2 Da (y(n)''(+) vs y(n)(-)) and by 15 Da (b(n)(+) vs c(n)(-))
      may be a useful method for determining whether a product ion is generated from
      the C-terminal or the N-terminal end of a peptide. In addition, a characteristic
      elimination of NH=C=NH from arginine residues is observed for deprotonated
      peptides.

PMID- 20127748
TI  - Learning curve in measurement of fetal frontomaxillary facial angle at 11-13
      weeks of gestation.
AB  - OBJECTIVE: To determine the number of ultrasound examinations required to train
      sonographers to accurately measure the fetal frontomaxillary facial (FMF) angle
      at 11-13 weeks of gestation. METHODS: Eight sonographers accredited for nuchal
      translucency thickness (NT) measurement (and with different levels of experience)
      were trained to measure the fetal FMF angle using specially acquired three
      dimensional (3D) volumes. Training was provided in cycles, and each cycle
      consisted of a training period on 20 randomly selected cases followed by an
      examination using 10 randomly selected cases. During training, the sonographer
      was informed of the true FMF angle value after each FMF angle measurement on a
      case-by-case basis. During examination, the difference between the measured and
      the true values of the FMF angle (i.e. the delta angle) was calculated. A
      measurement was considered accurate if the delta angle was less than 5 degrees .
      The sonographer was considered to be competent and the training finished if all
      10 examination cases satisfied this criterion. Otherwise, the sonographer would
      undergo further cycles of training-examination, until he/she became competent.
      RESULTS: The number of training cases required for a sonographer to become
      competent was 40 for two sonographers, 60 for one, 80 for one, 100 for two, 120
      for one and 140 for one, with a median of 90. The median number of failed cases
      reduced from 2.5 (out of 10) at the first cycle to 0 by the 7(th) cycle. As
      training cycles increased, the mean angle deviation and measurement time required
      both reduced significantly. The average delta angle of the passing examination
      cycle was 2.06 +/- 1.40 degrees . The number of training cases required to become
      competent in FMF angle measurement was 40 for the two most experienced trainees
      and 80, 120 and 140 for the three least experienced ones. CONCLUSIONS: We have
      demonstrated that competence in FMF angle measurement was achieved after a median
      number of 90 cases, with a range of up to 140. The number required was
      substantially lower, at 40 cases, among those with extensive experience of NT
      measurement.

PMID- 20127749
TI  - Ductus venosus blood flow velocity waveform in diabetic pregnancies.
AB  - OBJECTIVE: Maternal diabetes during pregnancy is associated with congenital
      cardiac malformations and hypertrophic cardiomyopathy. Blood flow in the ductus
      venosus (DV) has been postulated to reflect cardiac function. The aim of our
      study was to investigate if diabetic pregnancies exhibit abnormal DV
      hemodynamics, hence indicating changes in fetal cardiac function. METHODS: The
      pulsatility index of the DV (DV-PI) was analyzed retrospectively in 142 diabetic
      patients and compared to previously published DV-PI reference values from a non
      diabetic low-risk population. DV values were then correlated with maternal
      glycosylated hemoglobin (HbA1c). RESULTS: DV-PI was significantly higher in
      pregnancies complicated by either pre-existing insulin-dependent (DM) or
      gestational diabetes when compared with normal reference values. Increased DV-PI
      values were still evident in both diabetic groups when neonates that were small
      for-gestational age and neonates with pathological umbilical blood flow pattern
      were excluded from the analysis. In DM pregnancies a statistically significant
      correlation was found between DV-PI and maternal HbA1c. CONCLUSION: Diabetic
      pregnancies exhibit increased DV-PI values when compared to a normal low-risk
      pregnant population, possibly indicating a fetal cardiac effect.

PMID- 20127750
TI  - Viral infections associated with haemophagocytic syndrome.
AB  - Haemophagocytic syndrome (HPS) or haemophagocytic lymphohistiocytosis (HLH) is a
      rare disease caused by a dysfunction of cytotoxic T cells and NK cells. This T
      cell/NK cell dysregulation causes an aberrant cytokine release, resulting in
      proliferation/activation of histiocytes with subsequent haemophagocytosis.
      Histiocytic infiltration of the reticuloendothelial system results in
      hepatomegaly, splenomegaly, lymphadenopathy and pancytopenia ultimately leading
      to multiple organ dysfunctions. Common clinical features include high fevers
      despite broad spectrum antimicrobials, maculopapular rash, neurological symptoms,
      coagulopathy and abnormal liver function tests. Haemophagocytic syndrome can be
      either primary, i.e. due to an underlying genetic defect or secondary, associated
      with malignancies, autoimmune diseases (also called macrophage activation
      syndrome) or infections. Infectious triggers are most commonly due to viral
      infections mainly of the herpes group, with EBV being the most common cause. HPS
      can be fatal if untreated. Early recognition of the clinical presentation and
      laboratory abnormalities associated with HPS and prompt initiation of treatment
      can be life saving. HPS triggered by viral infections generally does not respond
      to specific antiviral therapy but may be treated with
      immunosuppressive/immunomodulatory agents and, in refractory cases, with bone
      marrow transplantation.

PMID- 20127751
TI  - Newly identified human rhinoviruses: molecular methods heat up the cold viruses.
AB  - Human rhinovirus (HRV) infections cause at least 70% of virus-related wheezing
      exacerbations and cold and flu-like illnesses. They are associated with otitis
      media, sinusitis and pneumonia. Annually, the economic impact of HRV infections
      costs billions in healthcare and lost productivity. Since 1987, 100 officially
      recognised HRV serotypes reside in two genetically distinct species; HRV A and
      HRV B, within the genus Enterovirus, family Picornaviridae. Sequencing of their
      approximately 7kb genomes was finalised in 2009. Since 1999, many globally
      circulating, molecularly-defined 'strains', perhaps equivalent to novel
      serotypes, have been discovered but remain uncharacterised. Many of these
      currently unculturable strains have been assigned to a proposed new species, HRV
      C although confusion exists over the membership of the species. There has not
      been sufficient sampling to ensure the identification of all strains and no
      consensus criteria exist to define whether clinical HRV detections are best
      described as a distinct strain or a closely related variant of a previously
      identified strain (or serotype). We cannot yet robustly identify patterns in the
      circulation of newly identified HRVs (niHRVs) or the full range of associated
      illnesses and more data are required. Many questions arise from this new found
      diversity: what drives the development of so many distinct viruses compared to
      other species of RNA viruses? What role does recombination play in generating
      this diversity? Are there species- or strain-specific circulation patterns and
      clinical outcomes? Are divergent strains sensitive to existing capsid-binding
      antivirals? This update reviews the findings that trigger these and other
      questions arising during the current cycle of intense rhinovirus discovery.

PMID- 20127752
TI  - Uterine venous blood flow in normal and complicated pregnancies: a methodological
      study.
AB  - OBJECTIVE: To investigate the possibility of recording Doppler flow signals from
      the maternal uterine veins (UtVs) during pregnancy and to assess the relationship
      between UtV signals and other Doppler parameters as well as pregnancy outcomes.
      METHODS: Transabdominal Doppler ultrasound examination of the UtVs on both sides
      of the uterus was performed in 40 normal and 44 high-risk singleton pregnancies
      at 23-39 weeks' gestation. The UtV was identified using color Doppler imaging and
      the flow velocity signals of the UtV and uterine artery (UtA) were recorded.
      Morphological examination of the placenta was carried out in 45 of the
      pregnancies (14 uncomplicated and 31 high-risk pregnancies). RESULTS: Flow
      velocity signals of the UtVs were recorded from at least one side of the uterus
      in all patients (success rate of 81 and 89% for the right and left UtV,
      respectively). Three types of flow-velocity pattern were identified: continuous
      non-pulsatile flow (Type I, n = 70), pulsatile flow with a notch touching the
      zero line (Type II, n = 6) and pulsatile flow with absent flow signals for part
      of the heart cycle (Type III, n = 8). The UtA pulsatility index was significantly
      higher in women with UtV Types II and III than in those with UtV Type I (P =
      0.039). Similarly, UtV Types II and III were more often found in pregnancies with
      bilateral UtA notching (P = 0.013) and with UtA score 3-4 (P = 0.024) than in
      those with normal UtA. No statistically significant association was found between
      the UtV flow pattern and abnormal histopathological findings in the placenta, or
      between the UtV and umbilical artery findings. CONCLUSION: It is possible to
      record Doppler signals from the UtVs in the late second and third trimesters of
      pregnancy. Pulsatile flow-velocity patterns of the UtVs are associated with
      abnormal UtA Doppler findings.

PMID- 20127753
TI  - Novel use of nanostructured alumina as an insecticide.
AB  - BACKGROUND: The worldwide need to produce an inexpensive and abundant food supply
      for a growing population is a great challenge that is further complicated by
      concerns about risks to environmental stability and human health triggered by the
      use of pesticides. The result is the ongoing development of alternative pest
      control strategies, and new, lower-risk insecticidal molecules. Among the recent
      technological advances in agricultural science, nanotechnology shows considerable
      promise, although its development for use in crop protection is in its initial
      stages. RESULTS: This study reports for the first time the insecticidal effect of
      nanostructured alumina. Two species were used as model organisms, Sitophilus
      oryzae L. and Rhyzopertha dominica (F.), which are major insect pests in stored
      food supplies throughout the world. Both species experienced significant
      mortality after 3 days of continuous exposure to treated wheat. Nine days after
      treatment, the median lethal doses (LD(50)) observed ranged from 127 to 235 mg
      kg(-1). CONCLUSION: Comparison of these results with recommended rates for
      commercial insecticidal dusts suggests that inorganic nanostructured alumina may
      provide a cheap and reliable alternative for control of insect pests. This study
      expands the frontiers for nanoparticle-based technologies in pest management.
      Further research is needed to identify its mode of action and its non-target
      toxicity, and to determine the potential of other nanostructured materials as
      pest control options for insects.

PMID- 20127754
TI  - Identification of two haplotypes of cytochrome oxidase subunit II (COII) gene of
      the Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera:
      Rhinotermitidae), in southern Mississippi.
AB  - BACKGROUND: Coptotermes formosanus Shiraki was accidentally introduced into the
      United States from Asia. The introduction of the pest has brought significant
      economic consequences. During the past decade, Mississippi has become a
      significantly infested state, partly due to the proximity to coastal port cities
      such as New Orleans. This study was initiated to investigate the origin and
      infestation route of C. formosanus in southern Mississippi. RESULTS: Twenty-eight
      colonies (21 colonies from Mississippi, six from Louisiana, one from China) were
      collected. Sequencing and analysis of 112 sequences revealed 15 haplotypes of
      cytochrome oxidase subunit II (COII) gene in the world. Two haplotypes of COII
      were identified in Mississippi. In addition, specific primers were designed and
      tested differentially to amplify characteristic fragments for verifying and
      surveying different genotypes of C. formosanus in the future. CONCLUSION: Of the
      two haplotypes identified in Mississippi, the GA group was identical to those
      reported previously in Georgia, Louisiana, Alabama and other infested states. The
      second haplotype, the AT group, was identified for the first time in southeastern
      United States. Sequence identity of the AT-group C. formosanus with those
      reported mainly in southeastern Asian countries provided evidence of at least two
      introductions of C. formosanus into the United States.

PMID- 20127755
TI  - Residues of the herbicide fenoxaprop-P-ethyl, its agronomic safener isoxadifen
      ethyl and their metabolites in rice after field application.
AB  - BACKGROUND: Fenoxaprop-P-ethyl is a herbicide used on cereals and in particular
      on rice, the degradation of which leads to several relevant metabolites. The
      herbicide is used together with an agronomic safener such as isoxadifen-ethyl,
      which also generates some metabolites. The present work was aimed at developing
      and validating an analytical method for the determination of the above parent
      compounds and their main metabolites in the edible fractions of rice. Parent
      compounds were extracted in acetonitrile and determined by gas chromatography
      with a mass spectrometer detector, while metabolites were extracted in
      acetonitrile and analysed by liquid chromatography tandem mass spectrometry.
      RESULTS: The method was validated through recovery tests in rice straw, grain and
      plant: accuracy was in the range 76-86% and 90-103% for parent compounds and
      metabolites respectively. Precision, as relative standard deviation, was in the
      range 3-11% and 6-17% for parent compounds and metabolites respectively. The
      limit of detection was 0.01 mg kg(-1) for each analyte, while the limit of
      quantification was set at 0.05 mg kg(-1). CONCLUSION: The analytical method is
      suitable for quantitative determination of each analyte considered in rice
      commodities.

PMID- 20127756
TI  - Jasmonic acid induces resistance to economically important insect pests in winter
      wheat.
AB  - BACKGROUND: Insect damage induces chemical changes in plants, and frequently
      these changes are part of a defensive response to the insect injury. Induced
      resistance was activated in winter wheat using a foliar application of synthetic
      jasmonic acid. Field trials were conducted to observe effects of jasmonic acid
      application on some wheat insects. Two wheat cultivars (Cubus and Tommi) were
      sprayed twice at growth stages (GS) 41 and 59 with two concentrations of jasmonic
      acid, along with control plots that were sprayed with water. RESULTS: There was a
      significant difference in the number of thrips and wheat blossom midges (WBM)
      among treatments in both cultivars. Plants in control plots had higher numbers of
      thrips and midges than in treated plots. There were higher numbers of thrips in
      the Tommi cultivar than in the Cubus cultivar, while the latter had higher
      numbers of WBM larvae than the Tommi cultivar. There was a positive correlation
      between WBM numbers and infested kernels in both cultivars. This study also
      indicated that jasmonic acid enhances the wheat yield in sprayed plots compared
      with control plots. CONCLUSIONS: The results indicate that jasmonic acid induced
      pest resistance in wheat plants and may act as a resistance mechanism of wheat
      against insect herbivores.

PMID- 20127757
TI  - Prenatal diagnosis of an isolated skin tumor of the chin.

PMID- 20127758
TI  - Intra- and interobserver repeatability of fetal cardiac examination using four
      dimensional spatiotemporal image correlation in each trimester of pregnancy.
AB  - OBJECTIVE: To assess the intra- and interobserver repeatability of the evaluation
      of fetal cardiac structures and measurements using spatiotemporal image
      correlation (STIC) technology in each trimester of pregnancy. METHODS: Four
      dimensional (4D)-STIC volumes from 150 low-risk pregnancies were acquired at
      first-, second- or third-trimester scan for later analysis by two different
      reviewers. A total of 19 items, including the evaluation of 14 structures as well
      as five measurements of the fetal heart, were evaluated. The reliability of
      qualitative variables was evaluated using Cohen's kappa and absolute agreement
      analysis while that of quantitative parameters was assessed using the intraclass
      correlation coefficient (ICC). RESULTS: Forty-five, 47 and 47 STIC volumes were
      included in the final analysis from the first, second and third trimesters,
      respectively. For the evaluation of cardiac structures, good or excellent intra-
      and interobserver agreement (kappa > 0.6) was obtained in 12/14 and 9/14,
      respectively, while absolute agreement was > 90% for most structures evaluated.
      Regarding the quantitative cardiac measurements, ICC values were above 0.90 for
      all but cardiac axis (intraobserver ICC, 0.81 and interobserver ICC, 0.61). There
      were no significant differences in the repeatability values observed for
      qualitative or quantitative parameters among the trimesters of pregnancy.
      CONCLUSION: Cardiac examination from 4D-STIC volumes showed a high repeatability
      between and within observers in each trimester of pregnancy.

PMID- 20127759
TI  - Glyphosate uncouples gas exchange and chlorophyll fluorescence.
AB  - BACKGROUND: Changes in chlorophyll fluorescence have often been advocated as a
      sensitive biomarker of plant stress, assuming that any kind of plant stress
      serious enough to affect plant growth will also affect photosynthesis. Glyphosate
      affects photosynthetic electron transport indirectly by inhibiting sink
      processes. The question is how fast this inhibition can be observed on CO(2)
      assimilation and ultimately on chlorophyll fluorescence? RESULTS: Experiments
      measuring CO(2) assimilation, conductance and chlorophyll fluorescence using four
      Kautsky curve parameters on barley (Hordeum vulgare L.) exposed to increasing
      doses of glyphosate showed a total cessation of CO(2) fixation and conductance
      without significant changes in chlorophyll fluorescence. The decrease in CO(2)
      fixation and conductance was significant 1 day after spraying and corresponded
      well to the decrease in biomass 5-7 days after spraying. CONCLUSION: A total
      cessation of CO(2) assimilation can take place without affecting chlorophyll
      fluorescence. Hypotheses concerning what happens to the energy from the
      photosynthetic apparatus that is not used for CO(2) assimilation are discussed.
      The results question the use of chlorophyll fluorescence as a universal indicator
      of stress on photosynthetic processes. Also, they demonstrate that changes in gas
      exchange parameters are more sensitive biomarkers for glyphosate toxicity
      compared with chlorophyll fluorescence.

PMID- 20127760
TI  - Differential distribution of tight junction proteins suggests a role for
      tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain.
AB  - The median eminence is one of the seven so-called circumventricular organs. It is
      located in the basal hypothalamus, ventral to the third ventricle and adjacent to
      the arcuate nucleus. This structure characteristically contains a rich capillary
      plexus and features a fenestrated endothelium, making it a direct target of blood
      borne molecules. The median eminence also contains highly specialized ependymal
      cells called tanycytes, which line the floor of the third ventricle. It has been
      hypothesized that one of the functions of these cells is to create a barrier that
      prevents substances in the portal capillary spaces from entering the brain. In
      this paper, we utilize immunohistochemistry to study the expression of tight
      junction proteins in the cells that compose the median eminence in adult mice.
      Our results indicate that tanycytes of the median eminence express occludin, ZO
      1, and claudin 1 and 5, but not claudin 3. Remarkably, these molecules are
      organized as a continuous belt around the cell bodies of the tanycytes that line
      the ventral part of the third ventricle. In contrast, the tanycytes at the
      periphery of the arcuate nucleus do not express claudin 1 and instead exhibit a
      disorganized expression pattern of occludin, ZO-1, and claudin 5. Consistent with
      these observations, permeability studies using peripheral or central injections
      of Evans blue dye show that only the tanycytes of the median eminence are joined
      at their apices by functional tight junctions, whereas tanycytes located at the
      level of the arcuate nucleus form a permeable layer. In conclusion, this study
      reveals a unique expression pattern of tight junction proteins in hypothalamic
      tanycytes, which yields new insights into their barrier properties.

PMID- 20127761
TI  - Comparative anatomy of the locus coeruleus in humans and nonhuman primates.
AB  - The locus coeruleus (LC) is a dense cluster of neurons that projects axons
      throughout the neuroaxis and is located in the rostral pontine tegmentum
      extending from the level of the inferior colliculus to the motor nucleus of the
      trigeminal nerve. LC neurons are lost in the course of several neurodegenerative
      disorders, including Alzheimer's and Parkinson's diseases. In this study we used
      Nissl staining and tyrosine hydroxylase (TH) immunoreactivity to compare the
      human LC with that of closely related primate species, including great and lesser
      apes, and macaque monkeys. TH catalyzes the initial and rate-limiting step in
      catecholamine biosynthesis. The number of TH-immunoreactive (TH-ir) neurons was
      estimated in each species using stereologic methods. In the LC of humans the mean
      total number of TH-ir neurons was significantly higher compared to the other
      primates. Because the total number of TH-ir neurons in the LC was highly
      correlated with the species mean volume of the medulla oblongata, cerebellum, and
      neocortical gray matter, we conclude that much of the observed phylogenetic
      variation can be explained by anatomical scaling. Notably, the total number of LC
      neurons in humans was most closely predicted by the nonhuman allometric scaling
      relationship relative to medulla size, whereas the number of LC neurons in humans
      was considerably lower than predicted according to neocortex and cerebellum
      volume.

PMID- 20127769
TI  - First approach to nitrogen-containing fused aromatic hydrocarbons as targets for
      organoelectronics utilizing a new transformation of O-protected diaryl methanols.
AB  - A new concise approach for the construction of heteroatom analogues of polycyclic
      aromatic benzo[g]quinoline, benzo[b]carbazole, and pyrido[b]carbazole systems via
      diaryl methanols is described. This transformation involves formation of a
      central benzene ring fused to two aromatic 5- or 6-membered rings of pyrrole
      and/or pyridine by using a combination of two aromatic aldehydes, of which at
      least one contains a ring nitrogen. Analysis of the UV and fluorescent
      properties, Stokes shifts, quantum yields in solution, and pi-stacking
      interactions in the crystal structures of the new materials was performed. These
      polycyclic aromatic compounds show potential as small-molecule organoelectronic
      materials.

PMID- 20127770
TI  - Versatile stamps in microcontact printing: transferring inks by molecular
      recognition and from ink reservoirs.
AB  - Microcontact printing is a heavily used surface modification method in materials
      and life science applications. This concept article focuses on the development of
      versatile stamps for microcontact printing that can be used to bind and release
      inks through molecular recognition or through an ink reservoir, the latter being
      used for the transfer of heavy inks, such as biomolecules and particles.
      Conceptually, such stamp properties can be introduced at the stamp surface or by
      changing the bulk stamp material; both lines of research will be reviewed here.
      Examples include supramolecular stamps with affinity properties, polymer-layer
      grafted PDMS stamps, and porous multilayer-grafted PDMS stamps for the first
      case, and hydrogel stamps and porous stamps made by phase-separation micromolding
      for the second. Potential directions for future advancement of this field are
      also discussed.

PMID- 20127771
TI  - Bimetallic Au-Ni nanoparticles embedded in SiO2 nanospheres: synergetic catalysis
      in hydrolytic dehydrogenation of ammonia borane.
AB  - Gold-nickel nanoparticles (NPs) of 3-4 nm diameter embedded in silica nanospheres
      of around 15 nm have been prepared by using [Au(en)(2)Cl(3)] and
      [Ni(NH(3))(6)Cl(2)] as precursors in a NP-5/cyclohexane reversed-micelle system,
      and by in situ reduction in an aqueous solution of NaBH(4)/NH(3)BH(3). Compared
      with monometallic Au@SiO(2) and Ni@SiO(2), the as-synthesized Au-Ni@SiO(2)
      catalyst shows higher catalytic activity and better durability in the hydrolysis
      of ammonia borane, generating a nearly stoichiometric amount of hydrogen. During
      the generation of H(2), the synergy effect between gold and nickel is apparent:
      The nickel species stabilizes the gold NPs and the existence of gold helps to
      improve the catalytic activity and durability of the nickel NPs.

PMID- 20127772
TI  - Specific induced circular dichroism and enhanced B to z transitions of duplexes
      stabilized by chromophore-linked alkynylnucleoside residues.
AB  - We have developed an induced circular dichroism (ICD) probe with a chromophore
      linked alkynyldeoxyribose skeleton for analyzing higher-order structures of DNA
      duplexes in the visible-light region. When CG-repeated oligonucleotides (ODNs)
      with the probe at their 5' ends adopted Z-form duplexes at a high NaCl
      concentration, strong ICD signals were observed at the absorptive region of the
      chromophore. On the other hand, their B-form duplexes, formed at a low NaCl
      concentration, produced a faint ICD signal. The specific ICD for the Z-form
      duplexes was found to appear only when the chromophores were attached at the 5'
      ends of each of the ODNs. Furthermore, the chromophoric alkynylnucleoside
      residues effectively promoted the B to Z transition of the ODN.

PMID- 20127773
TI  - A double donor-activated ruthenium(VII) catalyst: synthesis of enantiomerically
      pure THF-diols.

PMID- 20127774
TI  - Ferroelectricity in perovskites with s0 A-site cations: toward near-room
      temperature multiferroics.

PMID- 20127775
TI  - Characterization of a ruthenium(III)/NAMI-A adduct with bovine serum albumin that
      exhibits a high anti-metastatic activity.

PMID- 20127776
TI  - Aufbaureaktion redux: scalable production of precision hydrocarbons from AlR3
      (R=Et or iBu) by dialkyl zinc mediated ternary living coordinative chain-transfer
      polymerization.

PMID- 20127777
TI  - Nanometer-sized fluorous fullerene vesicles in water and on solid surfaces.

PMID- 20127778
TI  - Direct conversion of arylamines to pinacol boronates: a metal-free borylation
      process.

PMID- 20127779
TI  - Chiral tetrafluorobenzobarrelene ligands for the rhodium-catalyzed asymmetric
      cycloisomerization of oxygen- and nitrogen-bridged 1,6-enynes.

PMID- 20127780
TI  - In vivo production of functional single-chain Fv fragment with an N-terminal
      specific bio-orthogonal reactive group.

PMID- 20127781
TI  - Physical properties of water near a gold surface: a nanorheological analysis.
AB  - Water at room temperature is not simply a medium for which uniform properties can
      always be assumed. Water close to solid hydrophobic or hydrophilic surfaces has
      elasticity, which is measured by monitoring the quartz crystal microbalance (QCM)
      resonant frequency and resistance. Small additions of salt are shown to modify
      this elasticity. Furthermore, near the hydrophobic QCM gold electrode,
      undersaturated aqueous NaCl solutions present a high concentration of ion pairs,
      which is confirmed by atomic force microscopy through force versus distance
      measurements.

PMID- 20127782
TI  - Chemically tailored multivalent virus platforms: from drug delivery to catalysis.

PMID- 20127783
TI  - Deuteration of water enables self-organization of phospholipid-based reverse
      micelles.
AB  - Phospholipid-based reverse micelles are composed of branched cylinders. Their
      branching points are known to attract themselves and to slide along branches. The
      rate of this sliding is governed by the lifetime of H(D)-bonded water bridges
      between phospholipid molecules. This lifetime is increased when the water is
      deuterated. On condition that the water contains at least 40 D atoms%,
      water/dipalmitoylphosphatidylcholine (DPPC)/deuterated pyridine reverse micelles
      with the composition 1.1:1:250 (v/v) have been shown to self-organize into a
      liquid crystal in the 310-316 K temperature range. The mechanism of this self
      organization is unraveled by following the FTIR and (1)H NMR spectra of more
      concentrated micelles upon heating. During the preparation of micelles, pyridine
      (D(+))H(+) ions are formed. They give rise to hydron transfers, under the
      influence of the DPPC electric charges, evidenced by two broad FTIR absorptions
      above (BB1) and below (BB2) the nu(C-O) stretch. These hydron transfers occur
      along strong (D(+))H(+) bonds of pyridinium ions with pyridine (BB1) and DPPC C=O
      groups (BB2). The proton transfers at the interface of micelles, relayed in the
      continuous pyridine medium, create a tenuous link between separated micelles,
      thus facilitating their organization. Upon heating, DPPC heads shrink and DPPC
      chains expand to make wedge-shaped DPPC molecules. The micelles then change in
      shape: cylinders constrict and enclosed water drifts towards branching points,
      which swell. Branching points of neighboring micelles come into contact. Due to
      the deuteration of water these contacts are prolonged and H bonds are formed
      between DPPC molecules located in each branching point. Upon storage at 39
      degrees C, these branching points fuse. The lateral diffusion of DPPC molecules
      becomes free, as evidenced by a narrowing of all (1)H NMR resonances. Upon
      further heating, reorganization into a liquid crystal occurs.

PMID- 20127784
TI  - How far can we go? Quantum-chemical investigations of oxidation state +IX.
AB  - The highest known oxidation state of any element is +VIII. After the recent
      discovery of Ir(VIII)O(4) under cryogenic conditions, we have investigated the
      stability of cationic species [MO(4)](+) (M=Rh,Ir,Mt). Such compounds would
      formally represent the new oxidation state +IX, which is experimentally unknown
      so far for the whole periodic table. [IrO(4)](+) is predicted to be the most
      promising candidate. The calculated spin-orbit (SO) coupling shows only minor
      effects on the stability of the iridium species, whereas SO-coupling increases
      enormously for the corresponding Eka-Iridium (Meitnerium) complexes and
      destabilizes these.

PMID- 20127785
TI  - Synthesis and biological evaluation of pyridine-containing lipoxin A4 analogues.

PMID- 20127786
TI  - Diol appended quenchers for fluorescein boronic acid.
AB  - Fluorescein isothiocyanate is treated with 3-aminophenylboronic acid to provide a
      fluorescently tagged boronic acid derivative which is used to assess Forster
      resonance energy transfer (FRET) quenching upon boronate ester formation with a
      series of bespoke diol appended quenchers. Fluorescence spectroscopy comparison
      of quenching efficiency between treatment of fluorescein and its boronic acid
      appended congener with quencher appended diol reveals boronate ester formation
      (covalently linked) to be the more efficient regime and from the panel of
      quenchers which also included nucleosides.

PMID- 20127787
TI  - Clickable long-wave "mega-stokes" fluorophores for orthogonal chemoselective
      labeling of cells.

PMID- 20127788
TI  - Quinoneimido complexes of a metalloporphyrin: Isolation, X-ray crystal
      structures, and DFT calculations.

PMID- 20127789
TI  - Metal-free heterogeneous catalysis for sustainable chemistry.
AB  - The current established catalytic processes used in chemical industries use
      metals, in many cases precious metals, or metal oxides as catalysts. These are
      often energy-consuming and not highly selective, wasting resources and producing
      greenhouse gases. Metal-free heterogeneous catalysis using carbon or carbon
      nitride is an interesting alternative to some current industrialized chemical
      processes. Carbon and carbon nitride combine environmental acceptability with
      inexhaustible resources and allow a favorable management of energy with good
      thermal conductivity. Owing to lower reaction temperatures and increased
      selectivity, these catalysts could be candidates for green chemistry with low
      emission and an efficient use of the chemical feedstock. This Review highlights
      some recent promising activities and developments in heterogeneous catalysis
      using only carbon and carbon nitride as catalysts. The state-of-the-art and
      future challenges of metal-free heterogeneous catalysis are also discussed.

PMID- 20127790
TI  - Anion binding of N-(o-methoxybenzamido)thioureas: contribution of the
      intramolecular hydrogen bond in the N-benzamide moiety.
AB  - N-(o-methoxybenzamido)thioureas (2 X/2 Y) are found to show an enhanced anion
      binding affinity with binding constants over 10(7) mol(-1) L orders of magnitude
      for AcO(-) and a redshifted absorption of the anion binding complexes in
      acetonitrile (MeCN) relative to those of N-benzamidothioureas (1) that bear no o
      OMe in the N-benzamide moiety, despite the electron-donating character of o-OMe.
      Absorption of the anion-2 X/2 Y complex was shown to be of the same charge
      transfer nature as that of the anion-1 complex, but its dependence on substituent
      X is interestingly influenced by the o-MeOHNC=O six-membered-ring intramolecular
      hydrogen bond identified in 2 X/2 Y. Such an intramolecular hydrogen bond is
      suggested to be responsible for the enhanced anion binding affinity. In the
      presence of this intramolecular hydrogen bond, the anion binding constant of 2 X
      was found to be independent of substituent X at the N-phenyl ring, as in the case
      of 1, whereas that of 2 Y showed an amplified dependence on substituent Y at the
      N'-phenyl ring, but to a lower extent than that of 1. A similar ring
      intramolecular hydrogen bond was purported to exist in 2 Za, 2 Zd, and 2 Ze,
      which bear NHMe, F, and Cl as the ortho substituent in the N-benzamide moiety. In
      terms of the current roles of thiourea in not only anion recognition and sensing
      but also organocatalysis and crystal engineering, the present finding would be of
      significance for a wider structural diversity of smart thiourea derivatives with
      predesigned functions.

PMID- 20127791
TI  - Bromine-catalyzed aerobic oxidation of alcohols.

PMID- 20127792
TI  - Antimuscarinics and bladder outlet obstruction: From a contraindication to an
      indication?
AB  - AIM: To review if the existing data support the new concept that antimuscarinic
      agents can be used for the treatment of bladder outlet obstruction (BOO) with
      coexisting overactive bladder (OAB). METHOD: A literature search of Medline
      publications (up to 2008) on use of antimuscarinic agents for treatment BOO was
      performed and all data were presented. All relevant data from published studies
      in congress abstracts were as well included. RESULTS: The existing data show that
      this treatment effectively improves patient quality of life. Concerns about the
      possibility of urinary retention were shown to be unfounded. It seems that
      antimuscarinic agents do not affect voiding pressures and the use of
      antimuscarinic agents for BOO seems safe. CONCLUSIONS: The combination of an
      alpha-blocker and antimuscarinic agent for the treatment of BOO with concomitant
      OAB seems promising.

PMID- 20127793
TI  - Convergent and divergent validity of the Relationship Profile Test: investigating
      the relationship with attachment, interpersonal distress and psychological
      health.
AB  - The present study looked to illustrate the convergent and divergent validity of
      the Relationship Profile Test (RPT), which is a 30-item self-report measuring
      destructive overdependence, dysfunctional detachment, and healthy dependence. The
      RPT items are written to draw upon Bornstein's (19921993) 4-component model as
      well as other essential components of the dimension in question (Bornstein et
      al., 2003). The results reveal that the subscales of the RPT are related in
      predictable ways to scores on measures of adult attachment, interpersonal
      distress, and psychological health and well-being. The clinical implications of
      the results and the assessment of dependency in the clinical setting are
      discussed.

PMID- 20127794
TI  - Cognitive-behavioral treatment for chronic nightmares in trauma-exposed persons:
      assessing physiological reactions to nightmare-related fear.
AB  - Cognitive-behavioral treatments (CBTs) that target nightmares are efficacious for
      ameliorating self-reported sleep problems and psychological distress. However, it
      is important to determine whether these treatments influence objective markers of
      nightmare-related fear, because fear and concomitant physiological responses
      could promote nightmare chronicity and sleep disturbance. This randomized,
      controlled study (N=40) assessed physiological (skin conductance, heart rate,
      facial electromyogram) and subjective (displeasure, fear, anger, sadness,
      arousal) reactions to personally relevant nightmare imagery intended to evoke
      nightmare-related fear. Physiological assessments were conducted at pretreatment
      as well as 1-week, 3-months, and 6-months posttreatment. Results of mixed effects
      analysis of variance models suggested treatment reduced physiological and
      subjective reactions to nightmare imagery, gains that were generally maintained
      at the 6-month follow-up. Potential implications are discussed.

PMID- 20127795
TI  - Perceived barriers to psychological treatments and their relationship to
      depression.
AB  - In spite of repeated calls for research and interventions to overcome individual
      and systemic barriers to psychological treatments, little is known about the
      nature of these barriers. To develop a measure of perceived barriers to
      psychological treatment (PBPT), items derived from 260 participants were
      administered to 658 primary care patients. Exploratory factor analysis on half
      the sample resulted in 8 factors, which were supported by confirmatory factor
      analysis conducted on the other half. Associations generally supported the
      criterion validity of PBPT scales, with self-reported concurrent use of
      psychotherapy and psychotherapy attendance in the year after PBPT administration.
      Depression was associated with greater endorsement of barriers. These findings
      suggest that the PBPT may be useful in assessing perceived barriers.

PMID- 20127796
TI  - MicroRNA-196 represses Bach1 protein and hepatitis C virus gene expression in
      human hepatoma cells expressing hepatitis C viral proteins.
AB  - Hepatitis C virus (HCV) directly induces oxidative stress and liver injury.
      Bach1, a basic leucine zipper mammalian transcriptional repressor, negatively
      regulates heme oxygenase 1 (HMOX1), a key cytoprotective enzyme that has
      antioxidant and anti-inflammatory activities. microRNAs (miRNAs) are small
      noncoding RNAs ( approximately 22 nt) that are important regulators of gene
      expression. Whether and how miRNAs regulate Bach1 or HCV are largely unknown. The
      aims of this study were to determine whether miR-196 regulates Bach1, HMOX1,
      and/or HCV gene expression. HCV replicon cell lines (Con1 and 9-13) of the Con1
      isolate and J6/JFH1-based HCV cell culture system were used in this study. The
      effects of miR-196 mimic on Bach1, HMOX1, and HCV RNA, and protein levels were
      measured by way of quantitative real-time polymerase chain reaction (qRT-PCR) and
      Western blotting, respectively. The Dual Glo Luciferase Assay System was used to
      determine reporter activities. miR-196 mimic significantly down-regulated Bach1
      and up-regulated HMOX1 gene expression and inhibited HCV expression. Dual
      luciferase reporter assays demonstrated that transfection of miR-196 mimic
      resulted in a significant decrease in Bach1 3'-untranslated region (UTR)
      dependent luciferase activity but not in mutant Bach1 3'-UTR-dependent luciferase
      activity. Moreover, there was no detectable effect of mutant miR-196 on Bach1 3'
      UTR-dependent luciferase activity. CONCLUSION: miR-196 directly acts on the 3'
      UTR of Bach1 messenger RNA and translationally represses the expression of this
      protein, and up-regulates HMOX1. miR-196 also inhibits HCV expression in HCV
      replicon cell lines (genotype 1b) and in J6/JFH1 (genotype 2a) HCV cell culture
      system. Thus, miR-196 plays a role in both HMOX1/Bach1 expression and the
      regulation of HCV expression in human hepatocytes. Overexpression of miR-196
      holds promise as a potential novel strategy to prevent or ameliorate hepatitis C
      infection, and to protect against liver injury in chronic HCV infection.

PMID- 20127797
TI  - A novel molecule integrating therapeutic and diagnostic activities reveals
      multiple aspects of stem cell-based therapy.
AB  - Stem cells are promising therapeutic delivery vehicles; however pre-clinical and
      clinical applications of stem cell-based therapy would benefit significantly from
      the ability to simultaneously determine therapeutic efficacy and pharmacokinetics
      of therapies delivered by engineered stem cells. In this study, we engineered and
      screened numerous fusion variants that contained therapeutic (TRAIL) and
      diagnostic (luciferase) domains designed to allow simultaneous investigation of
      multiple events in stem cell-based therapy in vivo. When various stem cell lines
      were engineered with the optimized molecule, SRL(O)L(2)TR, diagnostic imaging
      showed marked differences in the levels and duration of secretion between stem
      cell lines, while the therapeutic activity of the molecule showed the different
      secretion levels translated to significant variability in tumor cell killing. In
      vivo, simultaneous diagnostic and therapeutic monitoring revealed that stem cell
      based delivery significantly improved pharmacokinetics and anti-tumor
      effectiveness of the therapy compared to intravenous or intratumoral delivery. As
      treatment for highly malignant brain tumor xenografts, tracking SRL(O)L(2)TR
      showed stable stem cell-mediated delivery significantly regressed peripheral and
      intracranial tumors. Together, the integrated diagnostic and therapeutic
      properties of SRL(O)L(2)TR answer critical questions necessary for successful
      utilization of stem cells as novel therapeutic vehicles.

PMID- 20127798
TI  - In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage
      potential of mesenchymal stem cells reveals a complex hierarchy of lineage
      commitment.
AB  - In regenerative medicine, bone marrow is a promising source of mesenchymal stem
      cells (MSCs) for a broad range of cellular therapies. This research addresses a
      basic prerequisite to realize the therapeutic potential of MSCs by developing a
      novel high-capacity assay to quantify the clonal heterogeneity in potency that is
      inherent to MSC preparations. The assay utilizes a 96-well format to (1) classify
      MSCs according to colony-forming efficiency as a measure of proliferation
      capacity and trilineage potential to exhibit adipo-, chondro-, and osteogenesis
      as a measure of multipotency and (2) preserve a frozen template of MSC clones of
      known potency for future use. The heterogeneity in trilineage potential of normal
      bone marrow MSCs is more complex than previously reported: all eight possible
      categories of trilineage potential were detected. In this study, the average
      colony-forming efficiency of MSC preparations was 55-62%, and tripotent MSCs
      accounted for nearly 50% of the colony-forming cells. The multiple phenotypes
      detected in this study infer a more convoluted hierarchy of lineage commitment
      than described in the literature. Greater cell amplification, colony-forming
      efficiency, and colony diameter for tri- versus unipotent clones suggest that MSC
      proliferation may be a function of potency. CD146 may be a marker of
      multipotency, with approximately 2-fold difference in mean fluorescence intensity
      between tri- and unipotent clones. The significance of these findings is
      discussed in the context of the efficacy of MSC therapies. The in vitro assay
      described herein will likely have numerous applications given the importance of
      heterogeneity to the therapeutic potential of MSCs.

PMID- 20127799
TI  - A mouse line expressing Sall1-driven inducible Cre recombinase in the kidney
      mesenchyme.
AB  - Sall1 is expressed in the metanephric mesenchyme in the developing kidney, and
      mice deficient in Sall1 show kidney agenesis or dysgenesis. Sall1 is also
      expressed elsewhere, including in the limb buds, anus, heart, and central nervous
      system. Dominant-negative mutations of Sall1 in mice and humans lead to
      developmental defects in these organs. Here, we generated a mouse line expressing
      tamoxifen-inducible Cre recombinase (CreER(T2)) under the control of the
      endogenous Sall1 promoter. Upon tamoxifen treatment, these mice showed genomic
      recombination in the tissues where endogenous Sall1 is expressed. When CreER(T2)
      mice were crossed with the floxed Sall1 allele, tamoxifen administration during
      gestation led to a significant decrease in Sall1 expression and small kidneys at
      birth, suggesting that Sall1 functions were disrupted. Furthermore, Sall1
      expression in the kidney was significantly reduced by neonatal tamoxifen
      treatment. The Sall1CreER(T2) mouse is a valuable tool for in vivo time-dependent
      and region-specific knockout and overexpression studies.

PMID- 20127800
TI  - Parabiosis model does not show presence of circulating osteoprogenitor cells.
AB  - The goal of this study was to determine the presence of osteoprogenitor cells in
      the peripheral blood. Experiments were conducted with a parabiosis model in which
      osteoblast specific transgenic mice (Col2.3GFP or hOC-GFP) were surgically joined
      with a transgenic mouse where herpes virus thymidine kinase gene is under the
      control of the collagen alpha1 promoter (Col2.3DeltaTK). This method permits
      conditional ablation of osteoblasts by ganciclovir (GCV) treatment. In parabionts
      treated with GCV for 15 days or 1.5-2 months, GFP (hOC-GFP or Col2.3GFP)
      expression was not detected in histological preparations or in marrow stromal
      cell cultures from the Col2.3DeltaTK parabiont. Finally, Col2.3GFP/Col2.3DeltaTK
      pairs were treated with GCV for 15 days and allowed to recover from GCV for 3
      months. Again there was a failure to detect Col2.3GFP expressing cells in the
      Col2.3DeltaTK parabiont. These observations, at least within the limits of this
      model system, allow the conclusion that osteoprogenitor cells do not readily
      circulate.

PMID- 20127802
TI  - Major histocompatibility complex class I expression and glial reaction influence
      spinal motoneuron synaptic plasticity during the course of experimental
      autoimmune encephalomyelitis.
AB  - Recent studies have shown that major histocompatibility complex class I (MHC I)
      expression directly influences the stability of nerve terminals. Also, the acute
      phase of experimental autoimmune encephalomyelitis (EAE) has shown a significant
      impact on inputs within the spinal cord. Therefore, the present work investigated
      the synaptic covering of motoneurons during the induction phase of disease and
      progressive remissions of EAE. EAE was induced in C57BL/6J mice, which were
      divided into four groups: normal, peak disease, first remission, and second
      remission. The animals were killed and their lumbar spinal cords processed for in
      situ hybridization (IH), immunohistochemistry, and transmission electron
      microscopy (TEM). The results indicated an increase in glial reaction during the
      peak disease. During this period, the TEM analysis showed a reduction in the
      synaptic covering of the motoneurons, corresponding to a reduction in
      synaptophysin immunolabeling and an increase in the MHC I expression. The IH
      analysis reinforced the immunolabeling results, revealing an increased expression
      of MHC I mRNA by motoneurons and nonneuronal cells during the peak disease and
      first remission. The results observed in both remission groups indicated a return
      of the terminals to make contact with the motoneuron surface. The ratio between
      excitatory and inhibitory inputs increased, indicating the potential for
      development of an excitotoxic process. In conclusion, the results presented here
      indicate that MHC I up-regulation during the course of EAE correlates with the
      periods of synaptic plasticity induced by the infiltration of autoreactive immune
      cells and that synaptic plasticity decreases after recurrent peaks of
      inflammation.

PMID- 20127801
TI  - Synaptic maturation of the Xenopus retinotectal system: effects of brain-derived
      neurotrophic factor on synapse ultrastructure.
AB  - Synaptogenesis is a dynamic process that involves structural changes in
      developing axons and dendrites as synapses form and mature. The visual system of
      Xenopus laevis has been used as a model to study dynamic changes in axons and
      dendrites as synapses form in the living brain and the molecular mechanisms that
      control these processes. Brain-derived neurotrophic factor (BDNF) contributes to
      the establishment and refinement of visual connectivity by modulating retinal
      ganglion cell (RGC) axon arborization and presynaptic differentiation. Here, we
      have analyzed the ultrastructural organization of the Xenopus retinotectal system
      to understand better the maturation of this synaptic circuit and the relation
      between synapse ultrastructure and the structural changes in connectivity that
      take place in response to BDNF. Expression of yellow fluorescent protein (YFP)
      followed by preembedding immunoelectron microscopy was used to identify RGC axons
      specifically in living tadpoles. Injection of recombinant BDNF was used to alter
      endogenous BDNF levels acutely in the optic tectum. Our studies reveal a rapid
      transition from a relatively immature synaptic circuit in which retinotectal
      synapses are formed on developing filopodial-like processes to a circuit in which
      RGC axon terminals establish synapses with dendritic shafts and spines. Moreover,
      our studies reveal that BDNF treatment increases the number of spine synapses and
      docked vesicle number at YFP-identified synaptic sites within 24 hours of
      treatment. These fine structural changes at retinotectal synapses are consistent
      with the role that BDNF plays in the functional maturation of synaptic circuits
      and with dynamic, rapid changes in synaptic connectivity during development.

PMID- 20127803
TI  - Targeted three-dimensional immunohistochemistry reveals localization of
      presynaptic proteins Bassoon and Piccolo in the rat calyx of Held before and
      after the onset of hearing.
AB  - Bassoon and Piccolo contribute to the cytomatrix of active zones (AZ), the sites
      of neurotransmitter release in nerve terminals. Here, we examined the 3D
      localization of Bassoon and Piccolo in the rat calyx of Held between postnatal
      days 9 and 21, the period of hearing onset characterized by pronounced structural
      and functional changes. Bassoon and Piccolo were identified by
      immunohistochemistry (IHC) on slices of the brainstem harboring calyces labeled
      with membrane-anchored green fluorescent protein (mGFP). By using confocal
      microscopy and 3D reconstructions, we examined the distribution of Bassoon and
      Piccolo in calyces delineated by mGFP. This allowed us to discriminate calyceal
      IHC signals from noncalyceal signals located in the spaces between the calyceal
      stalks, which could mimic a calyx-like distribution. We found that both proteins
      were arranged in clusters resembling the size of AZs. These clusters were located
      along the presynaptic membrane facing the principal cell, close to or overlapping
      with synaptic vesicle (SV) clusters. Only about 60% of Bassoon and Piccolo
      clusters overlapped, whereas the remaining clusters contained predominantly
      Bassoon or Piccolo, suggesting differential targeting of these proteins within a
      single nerve terminal and potentially heterogeneous AZs functional properties.
      The total number of Bassoon and Piccolo clusters, which may approximate the
      number of AZs, was 405 +/- 35 at P9 and 601 +/- 45 at P21 (mean +/- SEM, n = 12).
      Normalized to calyx volume at P9 and P21, the density of clusters was similar,
      suggesting that the absolute number of clusters, not density, may contribute to
      the functional maturation associated with hearing onset.

PMID- 20127805
TI  - Effects of incisor extraction on jaw and tongue motor representations within face
      sensorimotor cortex of adult rats.
AB  - Loss of teeth is associated with changes in somatosensory inputs and altered
      patterns of mastication, but it is unclear whether tooth loss is associated with
      changes in motor representations within face sensorimotor cortex of rats. We used
      intracortical microstimulation (ICMS) and recordings of cortically evoked muscle
      electromyographic (EMG) activities to test whether changes occur in the ICMS
      defined motor representations of the left and right jaw muscles [masseter,
      anterior digastric (LAD, RAD)] and tongue muscle [genioglossus (GG)] within the
      cytoarchitectonically defined face primary motor cortex (face-M1) and adjacent
      face primary somatosensory cortex (face-S1) 1 week following extraction of the
      right mandibular incisor in anesthetized (ketamine-HCl) adult male Sprague-Dawley
      rats. Under local and general anesthesia, an "extraction" group (n = 8) received
      mucoalveolar bone surgery and extraction of the mandibular right incisor. A "sham
      extraction" group (n = 6) received surgery with no extraction. A "naive" group (n
      = 6) had neither surgery nor extraction. Data were compared by using mixed-model
      repeated-measures ANOVA. Dental extraction was associated with a significantly
      increased number of sites within face-M1 and face-S1 from which ICMS evoked RAD
      EMG activities, a lateral shift of the RAD and LAD centers of gravity within face
      M1, shorter onset latencies of ICMS-evoked GG activities within face-M1 and face
      S1, and an increased number of sites within face-M1 from which ICMS
      simultaneously evoked RAD and GG activities. Our novel findings suggest that
      dental extraction may be associated with significant neuroplastic changes within
      the rat's face-M1 and adjacent face-S1 that may be related to the animal's
      ability to adapt to the altered oral state.

PMID- 20127806
TI  - Reinterpreting the magnetic resonance signs of hemodynamic impairment in the
      brains of multiple sclerosis patients from the perspective of a recent discovery
      of outflow block in the extracranial veins.
AB  - Multiple sclerosis patients examined with perfusion magnetic resonance (MR)
      imaging techniques have been found to have patterns of abnormal blood flow. These
      include prolonged mean transit time, a trend toward decreased cerebral blood flow
      in the area of plaques, and decreased cerebral blood flow and prolonged mean
      transit time within normal-appearing white matter. Increased cerebral blood flow
      and volume and decreased mean transit time (compared with the baseline values
      before the relapse) were found to precede the development of plaques. In
      addition, susceptibility-weighted imaging utilizing deoxyhemoglobin as the
      contrast has revealed that venous blood in cerebral veins of multiple sclerosis
      patients is less deoxygenated compared with healthy controls. All these findings
      were traditionally interpreted as a sign of local flow disturbances mediated by
      inflammatory and neurodegenerative processes. However, recent findings of
      significant stenoses in the extracranial veins that drain the brain and spinal
      cord shed new light on these MR results. With the assumption that a majority, if
      not all, of multiple sclerosis patients exhibit such extracranial venous
      obstacles, the perfusion MR images of multiple sclerosis patients should be
      reinterpreted. Perhaps ongoing MR studies with respect to extracranial venous
      hemodynamics may decipher some of the unsolved puzzles related to this neurologic
      disease.

PMID- 20127807
TI  - Synaptic plasticity after chemical deafening and electrical stimulation of the
      auditory nerve in cats.
AB  - The effects of deafness on brain structure and function have been studied using
      animal models of congenital deafness that include surgical ablation of the organ
      of Corti, acoustic trauma, ototoxic drugs, and hereditary deafness. This report
      describes the morphologic plasticity of auditory nerve synapses in response to
      ototoxic deafening and chronic electrical stimulation of the auditory nerve.
      Normal kittens were deafened by neonatal administration of neomycin that
      eliminated auditory receptor cells. Some of these cats were raised deaf, whereas
      others were chronically implanted with cochlear electrodes at 2 months of age and
      electrically stimulated for up to 12 months. The large endings of the auditory
      nerve, endbulbs of Held, were studied because they hold a key position in the
      timing pathway for sound localization, are readily identifiable, and exhibit
      deafness-associated abnormalities. Compared with those of normal hearing cats,
      synapses of ototoxically deafened cats displayed expanded postsynaptic densities,
      a 35.4% decrease in synaptic vesicle (SV) density, and a reduction in the somatic
      size of spherical bushy cells (SBCs). In comparison with normal hearing cats,
      ototoxically deafened cats that received cochlear stimulation had endbulbs that
      expressed postsynaptic densities (PSDs) that were statistically identical in
      size, showed a 48.1% reduction in SV density, and whose target SBCs had a 25.5%
      reduction in soma area. These results demonstrate that electrical stimulation via
      a cochlear implant in chemically deafened cats preserves PSD size but not other
      aspects of synapse morphology. This determination further suggests that the
      effects of ototoxic deafness are not identical to those of hereditary deafness.

PMID- 20127808
TI  - Aggressive behavior, related conduct problems, and variation in genes affecting
      dopamine turnover.
AB  - A number of dopamine-related genes have been implicated in the etiology of
      violent behavior and conduct problems. Of these genes, the ones that code for the
      enzymes that influence the turnover of dopamine (DA) have received the most
      attention. In this study, we investigated 12 genetic polymorphisms in four genes
      involved with DA functioning (COMT, MAOA and MAOB, and DbetaH) in 179
      incarcerated male Russian adolescents and two groups of matched controls: boys
      without criminal records referred to by their teachers as (a) "troubled-behavior
      free" boys, n=182; and (b) "troubled-behavior" boys, n=60. The participants were
      classified as (1) being incarcerated or not, (2) having the DSM-IV diagnosis of
      conduct disorder (CD) or not, and (3) having committed violent or nonviolent
      crimes (for the incarcerated individuals only). The findings indicate that,
      although no single genetic variant in any of the four genes differentiated
      individuals in the investigated groups, various linear combinations (i.e.,
      haplotypes) and nonlinear combinations (i.e., interactions between variants
      within and across genes) of genetic variants resulted in informative and robust
      classifications for two of the three groupings. These combinations of genetic
      variants differentiated individuals in incarceration vs. nonincarcerated and CD
      vs. no-CD groups; no informative combinations were established consistently for
      the grouping by crime within the incarcerated individuals. This study underscores
      the importance of considering multiple rather than single markers within
      candidate genes and their additive and interactive combinations, both with
      themselves and with nongenetic indicators, while attempting to understand the
      genetic background of such complex behaviors as serious conduct problems.

PMID- 20127809
TI  - Oligodendrogenesis in iron-deficient rats: effect of apotransferrin.
AB  - In rats, iron deficiency produces an alteration in myelin formation. However,
      there is limited information on the effects of this condition on oligodendroglial
      cell (OLGc) proliferation and maturation. In the present study, we further
      analyzed the hypomyelination associated with iron deficiency by studying the
      dynamics of oligodendrogenesis. Rats were fed control (40 mg Fe/kg) or iron
      deficient (4 mg Fe/kg) diets from gestation day 5 until postnatal day 3 (P3) or
      11 (P11). OLGc proliferation, migration and differentiation were investigated
      before and after an intracranial injection of apotransferrin at 3 days of age
      (P3). The proliferating cell population was evaluated at P3. Iron-deficient (ID)
      animals showed an increase in the oligodendrocyte precursors cell (OPC)
      population in comparison with controls. The overall pattern of migration of cells
      labeled with BrdU was investigated at P11. Iron deficiency increased the amount
      of BrdU(+) cells in the corpus callosum (CC) and decreased OLGc maturation and
      myelin formation. Changes in nerve conduction were analyzed by measuring visual
      evoked potentials. Latency and amplitude were significantly disturbed in ID rats
      compared with controls. Both parameters were substantially normalized when
      animals were treated with a single intracranial injection of 350 ng
      apotransferrin (aTf). The current results give support to the idea that iron
      deficiency increases the number of proliferating and undifferentiated cells in
      the CC compared with the control. Treatment with aTf almost completely reverted
      the effects of iron deficiency, both changing the migration pattern and
      increasing the number of mature cells in the CC and myelin formation.

PMID- 20127810
TI  - Expression of vascular endothelial growth factor receptor-3 mRNA in the rat
      developing forebrain and retina.
AB  - Vascular endothelial growth factor receptor (VEGFR)-3, a receptor for VEGF-C and
      VEGF-D, is expressed in neural progenitor cells, but there has been no
      comprehensive study of its distribution in the developing brain. Here, the
      temporal and cell-specific expression of VEGFR-3 mRNA was studied in the
      developing rat forebrain and eye. Expression appeared along the ventricular and
      subventricular zones of the lateral and third ventricles showing ongoing
      neurogenesis as early as embryonic day 13 but was progressively down-regulated
      during development and remained in the subventricular zone and rostral migratory
      stream of the adult forebrain. VEGFR-3 expression was also detectable in some
      differentiating and postmitotic neurons in the developing cerebral cortex,
      including Cajal-Retzius cells, cortical plate neurons, and subplate neurons.
      Expression in the subplate increased significantly during the early postnatal
      period but was absent by postnatal day 14. It was also highly expressed in
      nonneural tissues of the eye during development, including the retinal pigment
      epithelium, the retinal ciliary margin, and the lens, but persisted in a subset
      of cells in the pigmented ciliary epithelium of the adult eye. In contrast, there
      was weak or undetectable expression in the early neural retina, but a subset of
      retinal neurons in the postnatal and mature retina showed intense signals. These
      unique spatiotemporal mRNA expression patterns suggest that VEGFR-3 might mediate
      the regulation of both neurogenesis and adult neuronal function in the rat
      forebrain and eye.

PMID- 20127811
TI  - Dynamin 1 depletion and memory deficits in rats treated with Abeta and cerebral
      ischemia.
AB  - Alzheimer's disease (AD) is progressive dementia with senile plaques composed of
      beta-amyloid (Abeta). Recent studies suggest that synaptic dysfunction is one of
      the earliest events in the pathogenesis of AD. Here we provide the first
      experimental evidence that a change in the level of dynamin 1 induced by Abeta
      correlates with memory impairment in vivo. We treated rats with transient
      cerebral ischemia with oligomeric forms of Abeta (Abeta oligomers), including
      dimers, trimers, and tetramers, intracerebroventricularly. The combination of
      Abeta oligomers and cerebral ischemia, but not cerebral ischemia alone,
      significantly impaired memory and decreased the level of dynamin 1, which plays a
      critical role in synaptic vesicle recycling, but did not affect the levels of
      other synaptic proteins, such as synaptophysin and synaptobrevin, in the
      hippocampus. Furthermore, the N-methyl-D-aspartate (NMDA) receptor antagonist
      memantine prevented memory impairment and dynamin 1 degradation, suggesting that
      these changes might be mediated by NMDA receptors. These results suggest that
      Abeta oligomers induce memory impairment via dynamin 1 degradation, which may
      imply that dynamin 1 degradation is one of the causes of synaptic dysfunction in
      AD.

PMID- 20127812
TI  - Postnatal changes in tryptophan hydroxylase and serotonin transporter
      immunoreactivity in multiple brainstem nuclei of the rat: implications for a
      sensitive period.
AB  - Previously, we found that the brainstem neuronal network in normal rats undergoes
      abrupt neurochemical, metabolic, and physiological changes around postnatal days
      (P) 12-13, a critical period when the animal's response to hypoxia is also the
      weakest. This has special implications for sudden infant death syndrome (SIDS),
      insofar as seemingly normal infants succumb to SIDS when exposed to respiratory
      stressors (e.g., hypoxia) during a narrow postnatal window. Because an abnormal
      serotonergic system has recently been implicated in SIDS, we conducted a large
      scale investigation of the 5-HT-synthesizing enzyme tryptophan hydroxylase (TPH)
      and serotonin transporter (SERT) with semiquantitative immunohistochemistry in
      multiple brainstem nuclei of normal rats aged P2-21. We found that 1) TPH and
      SERT immunoreactivity in neurons of raphe magnus, obscurus, and pallidus and SERT
      in the neuropil of the pre-Botzinger complex, nucleus ambiguus, and
      retrotrapezoid nucleus were high at P2-11 but decreased markedly at P12 and
      plateaued thereafter until P21; 2) SERT labeling in neurons of the lateral
      paragigantocellular nucleus (LPGi) and parapyramidal region (pPy) was high at P2
      9 but fell significantly at P10, followed by a gradual decline until P21; 3) TPH
      labeling in neurons of the ventrolateral medullary surface was stable except for
      a significant fall at P12; and 4) TPH and SERT immunoreactivity in a number of
      other nuclei was relatively stable from P2 to P21. Thus, multiple brainstem
      nuclei exhibited a significant decline in TPH and SERT immunoreactivity during
      the critical period, suggesting that such normal development can contribute to a
      narrow window of vulnerability in postnatal animals.

PMID- 20127813
TI  - DMXB (GTS-21) ameliorates the cognitive deficits in beta amyloid(25-35(-) )
      injected mice through preventing the dysfunction of alpha7 nicotinic receptor.
AB  - Intracerebroventricular injection of beta-amyloid(25-35) (Abeta(25-35)) in mice
      leads to cognitive deficits with the dysfunction of alpha7 nicotinic
      acetylcholine receptor (alpha7nAChR) within 1-2 weeks in a dose-dependent manner.
      The present study focused on the effect of DMXB, a selective alpha7nAChR agonist,
      on Abeta(25-35) (3 nmol)-impaired spatial memory and alpha7nAChR function. We
      found that the treatment with DMXB on days 1-10 after Abeta(25-35) injection dose
      dependently prevented Abeta(25-35)-induced impairment of acquisition performance
      and probe trail test in Morris water maze. Importantly, the treatment with DMXB
      (1 mg/kg) perfectly prevented Abeta(25-35)-induced depression of alpha7nAChR
      response, which was associated with improving the probability of presynaptic
      glutamate release and the induction of high-frequency stimulation (HFS)-dependent
      long-term potentiation (LTP) in hippocampal Schaffer collaterale-CA1 synapse.
      Furthermore, although either the basal level of extracellular signal-regulated
      kinase 2 (ERK2) or its phosphorylation in the hippocampus had no difference
      between control and Abeta(25-35) mice, the Abeta(25-35) injection significantly
      attenuated HFS-triggered increase in ERK2 phosphorylation. The treatment with
      DMXB also rescued the ERK2 phosphorylation triggered by HFS in Abeta(25-35) mice
      that is required for LTP induction. This study firstly provides in vivo evidence
      that the anti-amnesic effect of DMXB is likely due to preventing the Abeta(25-35)
      induced dysfunction of alpha7nAChR.

PMID- 20127814
TI  - Thyroid hormone enhances transected axonal regeneration and muscle reinnervation
      following rat sciatic nerve injury.
AB  - Improvement of nerve regeneration and functional recovery following nerve injury
      is a challenging problem in clinical research. We have already shown that
      following rat sciatic nerve transection, the local administration of
      triiodothyronine (T3) significantly increased the number and the myelination of
      regenerated axons. Functional recovery is a sum of the number of regenerated
      axons and reinnervation of denervated peripheral targets. In the present study,
      we investigated whether the increased number of regenerated axons by T3-treatment
      is linked to improved reinnervation of hind limb muscles. After transection of
      rat sciatic nerves, silicone or biodegradable nerve guides were implanted and
      filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions
      (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with
      rhodamine alpha-bungarotoxin and neurofilament antibody. Four weeks after
      surgery, most end-plates (EPs) of operated limbs were still denervated and no
      effect of T3 on muscle reinnervation was detected at this stage of nerve repair.
      In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the
      reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly
      higher recovery of size and shape complexity of reinnervated EPs and also by
      increased acetylcholine receptor (AChRs) density on post synaptic membranes
      compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is
      confirmed by a higher index of compound muscle action potentials recorded in
      gastrocnemius muscles. In conclusion, our results provide for the first time
      strong evidence that T3 enhances the restoration of NMJ structure and improves
      synaptic transmission.

PMID- 20127815
TI  - The comparison of mouse full metallothionein-1 versus alpha and beta domains and
      metallothionein-1-to-3 mutation following traumatic brain injury reveals
      different biological motifs.
AB  - Traumatic injury to the brain is one of the leading causes of injury-related
      death or disability, but current therapies are limited. Previously it has been
      shown that the antioxidant proteins metallothioneins (MTs) are potent
      neuroprotective factors in animal models of brain injury. The exogenous
      administration of MTs causes effects consistent with the roles proposed from
      studies in knock-out mice. We herewith report the results comparing full mouse MT
      1 with the independent alpha and beta domains, alone or together, in a cryoinjury
      model. The lesion of the cortex caused the mice to perform worse in the
      horizontal ladder beam and the rota-rod tests; all the proteins showed a modest
      effect in the former test, while only full MT-1 improved the performance of
      animals in the rota-rod, and the alpha domain showed a rather detrimental effect.
      Gene expression analysis by RNA protection assay demonstrated that all proteins
      may alter the expression of host-response genes such as GFAP, Mac1 and ICAM, in
      some cases being the beta domain more effective than the alpha domain or even the
      full MT-1. A MT-1-to-MT-3 mutation blunted some but not all the effects caused by
      the normal MT-1, and in some cases increased its potency. Thus, splitting the two
      MT-1 domains do not seem to eliminate all MT functions but certainly modifies
      them, and different motifs seem to be present in the protein underlying such
      functions.

PMID- 20127816
TI  - Inflammasome signaling at the heart of central nervous system pathology.
AB  - Neuroinflammation is a complex innate response of neural tissue against harmful
      effects of diverse stimuli viz., pathogens, damaged cells and irritants within
      the Central Nervous System (CNS). Studies show that multiple inflammatory
      mediators including cytokines, chemokines and prostaglandins are elevated in the
      Cerebrospinal Fluid (CSF) and in post-mortem brain tissues of patients with
      history of neuroinflammatory conditions as well as neurodegenerative disorders
      like Alzheimer's disease, Parkinson's disease and Multiple Sclerosis. The innate
      immunity mediators in the brain, namely microglia and astrocytes, express certain
      Pattern Recognition Receptors (PRRs), which are always on 'high-alert' for
      pathogens or other inflammatory triggers and participate in the assembly and
      activation of the inflammasome. The inflammasome orchestrates the activation of
      the precursors of proinflammatory caspases, which in turn, cleave the precursor
      forms of interleukin-1beta, IL-18 and IL-33 into their active forms; the
      secretion of which leads to a potent inflammatory response, and/or influences the
      release of toxins from glial and endothelial cells. Altered expression of
      inflammasome mediators can either promote or inhibit neurodegenerative processes.
      Therefore, modulating the inflammasome machinery seems a better combat strategy
      than summarily suppressing all inflammation in most neuroinflammatory conditions.
      In the current review we have surveyed the identified triggers and pathways of
      inflammasome activation and the following events which ultimately accomplish the
      innate inflammatory response in the CNS, with a goal to provide an analytical
      insight into disease pathogenesis that might provide cues for devising novel
      therapeutic strategies.

PMID- 20127817
TI  - Does controlling for comorbidity matter? DSM-oriented scales and violent
      offending in Chicago youth.
AB  - Mental health problems have long been linked to antisocial behaviors. Despite an
      impressive body of literature demonstrating this relationship and claims that
      comorbidity matters, few studies examine comorbidity using multiple distinct
      mental health indicators, with most studies instead adopting single or composite
      mental health measures. This study tested separate and comorbid effects of five
      DSM-oriented mental health issues on self-reported violence using a community
      based sample of Chicago youths from the Project on Human Development in Chicago
      Neighborhoods. Moreover, it utilized both primary caregiver and youth self
      reports of psychopathology across four developmental stages of childhood and
      adolescence. When examined separately, the results indicated
      affective/depressive, anxiety, attention deficit hyperactivity, and oppositional
      defiant/antisocial personality problems independently predicted violence. When
      considering comorbidity, however, only oppositional defiant and antisocial
      personality problems significantly predicted violence at any stage, regardless of
      informant type. Implications for future studies and policy are discussed.

PMID- 20127819
TI  - Induction of parkinsonism-related proteins in the spinal motor neurons of
      transgenic mouse carrying a mutant SOD1 gene.
AB  - Amyotrophic lateral sclerosis is a progressive and fatal disease caused by
      selective death of motor neurons, and a number of these patients carry mutations
      in the superoxide dismutase 1 (SOD1) gene involved in ameliorating oxidative
      stress. Recent studies indicate that oxidative stress and disruption of
      mitochondrial homeostasis is a common mechanism for motor neuron degeneration in
      amyotrophic lateral sclerosis and the loss of midbrain dopamine neurons in
      Parkinson's disease. Therefore, the present study investigated the presence and
      alterations of familial Parkinson's disease-related proteins, PINK1 and DJ-1, in
      spinal motor neurons of G93ASOD1 transgenic mouse model of amyotrophic lateral
      sclerosis. Following onset of disease, PINK1 and DJ-1 protein expression
      increased in the spinal motor neurons. The activated form of p53 also increased
      and translocated to the nuclei of spinal motor neurons, followed by increased
      expression of p53-activated gene 608 (PAG608). This is the first report
      demonstrating that increased expression of PAG608 correlates with activation of
      phosphorylated p53 in spinal motor neurons of an amyotrophic lateral sclerosis
      model. These results provide further evidence of the profound correlations
      between spinal motor neurons of amyotrophic lateral sclerosis and parkinsonism
      related proteins.

PMID- 20127818
TI  - Ret-PCP2 colocalizes with protein kinase C in a subset of primate ON cone bipolar
      cells.
AB  - Purkinje cell protein 2 (PCP2), a member of the family of guanine dissociation
      inhibitors and a strong interactor with the G-protein subunit G alpha(o),
      localizes to retinal ON bipolar cells. The retina-specific splice variant of
      PCP2, Ret-PCP2, accelerates the light response of rod bipolar cells by modulating
      the mGluR6 transduction cascade. All ON cone bipolar cells express mGluR6 and G
      alpha(o), but only a subset expresses Ret-PCP2. Here we test the hypothesis that
      Ret-PCP2 contributes to shaping the various temporal bandwidths of ON cone
      bipolar cells in monkey retina. We found that the retinal splice variants in
      monkey and mouse are similar and longer than the cerebellar variants. Ret-PCP2 is
      strongly expressed by diffuse cone bipolar type 4 cells (DB4; marked with anti
      PKCalpha) and weakly expressed by midget bipolar dendrites (labeled by antibodies
      against G alpha(o), G gamma 13, or mGluR6). Ret-PCP2 is absent from diffuse cone
      bipolar type 6 (DB6; marked with anti-CD15) and blue cone bipolar cells (marked
      with anti-CCK precursor). Thus, cone bipolar cells that terminate in stratum 3 of
      the inner plexiform layer (DB4) express more Ret-PCP2 than those that terminate
      in strata 3 + 4 (midget bipolar cells), and these in turn express more than those
      that terminate in stratum 5 (DB6 and blue cone bipolar cells). This expression
      pattern approximates the arborization of ganglion cells (GC) with different
      temporal bandwidths: parasol GCs stratifying near stratum 3 are faster than
      midget GCs stratifying in strata 3 + 4, and these are probably faster than the
      sluggish GCs that arborize in stratum 5.

PMID- 20127820
TI  - NRAGE is a negative regulator of nerve growth factor-stimulated neurite outgrowth
      in PC12 cells mediated through TrkA-ERK signaling.
AB  - NRAGE, also denominated as MAGE-D1 or Dlxin-1, is firstly identified as a
      molecule interacting with NGF low affinity receptor p75NTR. It facilitates cell
      cycle arrest and NGF-dependent neuronal apoptosis. Here we report that NRAGE is
      downregulated while p75NTR is upregulated during the process of NGF-induced
      neuronal differentiation of PC12 cells. Knockdown of NRAGE by RNA interference
      accelerates NGF-mediated neurite outgrowth. In addition, in the NRAGE-suppressed
      cells, NGF-induced ERK activation is increased and this activation is MEK
      dependent. Conversely, NRAGE overexpression significantly represses NGF-induced
      ERK activation. Further studies revealed that NRAGE downregulates TrkA expression
      through a post-transcriptional manner and thereby blocks NGF-induced TrkA
      phosphrylation at tyrosine-490. Altogether, these data indicate for the first
      time that NRAGE is an endogenous inhibitor for NGF-induced neuronal
      differentiation of PC12 cells by regulating TrkA-ERK signaling.

PMID- 20127821
TI  - Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain
      development.
AB  - Mutations in the human L1CAM gene cause X-linked hydrocephalus and MASA (Mental
      retardation, Aphasia, Shuffling gait, Adducted thumbs) syndrome. In vitro studies
      have shown that the L1 cytoplasmic domain (L1CD) is involved in L1 trafficking,
      neurite branching, signaling, and interactions with the cytoskeleton. L1cam
      knockout (L1(KO)) mice have hydrocephalus, a small cerebellum, hyperfasciculation
      of corticothalamic tracts, and abnormal peripheral nerves. To explore the
      function of the L1CD, we made three new mice lines in which different parts of
      the L1CD have been altered. In all mutant lines L1 protein is expressed and
      transported into the axon. Interestingly, these new L1CD mutant lines display
      normal brain morphology. However, the expression of L1 protein in the adult is
      dramatically reduced in the two L1CD mutant lines that lack the ankyrin-binding
      region and they show defects in motor function. Therefore, the L1CD is not
      responsible for the major defects observed in L1(KO) mice, yet it is required for
      continued L1 protein expression and motor function in the adult.

PMID- 20127823
TI  - Development of mucoadhesive films for buccal administration of flufenamic acid:
      Effect of cyclodextrin complexation.
AB  - A new mucoadhesive film for topical administration in the oral cavity of
      flufenamic acid, a poorly soluble anti-inflammatory drug, has been developed,
      using complexation with hydroxypropyl-beta-cyclodextrin (HPbetaCD) to improve
      drug dissolution and release rate. Buccal films were prepared utilising chitosan
      as mucoadhesive polymer, KollicoatIR as film-forming polymer and glycerol as
      plasticiser. Different combinations of these components were used and the
      obtained films were characterised for weight, thickness, swelling, mucoadhesive
      and mechanical properties. The film containing chitosan 2%, glycerol 7.5% and
      KollicoatIR 1% showed the best properties for the development of the film
      formulation. The selected film was loaded with the plain drug and its
      colyophilised and coground products with HPbetaCD, and in vitro release studies
      in simulated saliva were performed. The improved drug dissolution properties,
      obtained by complexation with HPbetaCD, were critical to achieve complete release
      from film formulation during 4-5 h. On the contrary, film loaded with the plain
      drug showed incomplete release, not exceeding 70% release after 5 h. The
      developed film formulation containing the drug as complex with HPbetaCD can
      assure a prolonged drug release directly at the inflammation site and can be
      proposed as a new therapeutic tool in the treatment of oral mucosa inflammations.

PMID- 20127822
TI  - Immunocytochemical localization of synaptic proteins to photoreceptor synapses of
      Drosophila melanogaster.
AB  - The location of proteins that contribute to synaptic function has been widely
      studied in vertebrate synapses, far more than at model synapses of the
      genetically manipulable fruit fly, Drosophila melanogaster. Drosophila
      photoreceptor terminals have been extensively exploited to characterize the
      actions of synaptic genes, and their distinct and repetitive synaptic
      ultrastructure is anatomically well suited for such studies. Synaptic release
      sites include a bipartite T-bar ribbon, comprising a platform surmounting a
      pedestal. So far, little is known about the composition and precise location of
      proteins at either the T-bar ribbon or its associated synaptic organelles,
      knowledge of which is required to understand many details of synaptic function.
      We studied the localization of candidate proteins to pre- or postsynaptic
      organelles, by using immuno-electron microscopy with the pre-embedding method,
      after first validating immunolabeling by confocal microscopy. We used monoclonal
      antibodies against Bruchpilot, epidermal growth factor receptor pathway substrate
      clone 15 (EPS-15), and cysteine string protein (CSP), all raised against a fly
      head homogenate, as well as sea urchin kinesin (antibody SUK4) and Discs large
      (DLG). All these antibodies labeled distinct synaptic structures in photoreceptor
      terminals in the first optic neuropil, the lamina, as did rabbit anti-DPAK
      (Drosophila p21 activated kinase) and anti-Dynamin. Validating reports from light
      microscopy, immunoreactivity to Bruchpilot localized to the edge of the platform,
      and immunoreactivity to SUK4 localized to the pedestal of the T-bar ribbon. Anti
      DLG recognized the photoreceptor head of capitate projections, invaginating
      organelles from surrounding glia. For synaptic vesicles, immunoreactivity to EPS
      15 localized to sites of endocytosis, and anti-CSP labeled vesicles lying close
      to the T-bar ribbon. These results provide markers for synaptic sites, and a
      basis for further functional studies.

PMID- 20127824
TI  - Examination of the ability of the nasal administration route to confer a brain
      exposure advantage for three chemical inhibitors of P-glycoprotein.
AB  - The central nervous system (CNS), efficiently isolated from the systemic
      circulation by the blood-brain barrier (BBB), represents a challenging
      therapeutic target. For CNS-targeted agents, augmenting brain exposure by
      increasing blood drug concentrations often is prohibited by systemic toxicity.
      Therefore, a means for selectively increasing brain exposure, while minimizing
      systemic exposure, would be desirable. Limited evidence has indicated that
      nasally-administered compounds can penetrate into brain, although the selectivity
      of this approach is unclear. This study demonstrated a distinct, but compound
      specific, advantage of the nasal administration route in conferring selective CNS
      delivery (defined as a brain exposure advantage; BEA). Brain and systemic
      concentrations of three P-glycoprotein-inhibiting agents were evaluated following
      single nasal or systemic doses to mice, and the influence of administration route
      on brain exposure (absolute BEA) and on brain-to-blood partitioning (relative
      BEA) was calculated. Relative and absolute BEA differed markedly among rifampin,
      quinidine, and GF120918, with relative BEA ranging between 1.53- and 809-fold and
      absolute BEA between 0.114- and 9.19-fold. Although substantial increases in
      brain exposure and partitioning in conjunction with nasal administration were
      demonstrated, the utility of this approach may be limited by inability to deliver
      a therapeutically relevant mass of drug to the brain.

PMID- 20127825
TI  - Drug-polymer solubility and miscibility: Stability consideration and practical
      challenges in amorphous solid dispersion development.
AB  - Drug-polymer solid dispersion has been demonstrated as a feasible approach to
      formulate poorly water-soluble drugs in the amorphous form, for the enhancement
      of dissolution rate and bioperformance. The solubility (for crystalline drug) and
      miscibility (for amorphous drug) in the polymer are directly related to the
      stabilization of amorphous drug against crystallization. Therefore, it is
      important for pharmaceutical scientists to rationally assess solubility and
      miscibility in order to select the optimal formulation (e.g., polymer type, drug
      loading, etc.) and recommend storage conditions, with respect to maximizing the
      physical stability. This commentary attempts to discuss the concepts and
      implications of the drug-polymer solubility and miscibility on the stabilization
      of solid dispersions, review recent literatures, and propose some practical
      strategies for the evaluation and development of such systems utilizing a working
      diagram.

PMID- 20127826
TI  - Theoretical versus empirical allometry: Facts behind theories and application to
      pharmacokinetics.
AB  - Although, no credible data are available, it is widely believed that the
      pharmacokinetic parameters such as clearance, volume of distribution, and
      elimination half-life can be scaled with a fixed exponent of 0.75, 1.0, and 0.25,
      respectively. However, logically it is difficult to perceive that the exponents
      of allometry for a given parameter will revolve around a fixed number. Over the
      last 80 years, theoretical biologists and physiologists are entangled in an
      argument whether the exponent of basal metabolic rate against body weight is 0.67
      or 0.75. There are evidence for and against these two exponents. However, in
      depth investigative works suggest that there is not really any universal exponent
      for any allometrically related parameter and the exponent of allometry depends on
      several factors. The main focus of this report is to show the readers that there
      is enough evidence from experimental data that negate the notion of fixed
      exponents in biology, physiology, and pharmacokinetics. In short, the notion of a
      fixed exponent is theoretical and there is no evidence that the exponent of a
      physiological or pharmacokinetic parameter revolves around a fixed number.

PMID- 20127827
TI  - Hyperglycemia and hypoxia are interrelated in their teratogenic mechanism:
      studies on cultured rat embryos.
AB  - BACKGROUND: Hyperglycemia and hypoxia are well-known teratogens that may affect
      many animal species, including man. One of the main mechanisms of teratogenic
      action of both seems to be increased oxidative stress. The purpose of this study
      was to evaluate the hypothesis that in the developing embryo hyperglycemia also
      leads to hypoxia, both resulting in oxidative damage. METHODS: The study was
      performed on 10.5-day-old rat embryos of the regular Sabra strain cultured for 28
      hours in hyperglycemic or hypoxic conditions. Embryonic growth and rate of
      anomalies was assessed at the end of the culture period. The embryonic oxidative
      damage was investigated by studying the levels of Malondialdehyde (MDA) to
      determine the lipid peroxidation. The redox status was studied by measuring the
      activity of Catalase-like (CAT) and Super Oxide Dismutase (SOD) enzymes and the
      amount of Low Molecular Weight Antioxidants (LMWA). In addition, we studied by
      immunohistochemistry in the embryos and yolk sacs the amount of nitrotyrosine as
      an additional marker for the extent of oxidative stress. The amounts of the redox
      and hypoxia sensitive transcription factors HIF1alpha, NFkB, and IkB were also
      studied by immunohistochemistry. RESULTS: Both hyperglycemia and hypoxia
      increased the rate of congenital anomalies mainly of the heart, neural tube, and
      brain. Embryonic growth and scoring were decreased only by hypoxia. Both
      hyperglycemia and hypoxia increased embryonic oxidative stress as evidenced by
      increased lipid peroxidation, increased nitrotyrosine and LMWA, but only minimal
      changes in CAT and SOD activity. Severe hyperglycemia also caused hypoxia, as
      evidenced by increased HIF1alpha. Thus, there seems to be an interrelation
      between hyperglycemia and hypoxia, both resulting in embryonic damage apparently
      by enhanced oxidative stress. CONCLUSIONS: Both hyperglycemia and hypoxia seem to
      exert their embryotoxicity through a similar mechanism of increased oxidative
      stress in the embryo in a stage when its antioxidant capacity is still weak.
      Moreover, hyperglycemia also seems to induce hypoxia, intensifying diabetes
      induced embryopathy.

PMID- 20127828
TI  - Cardiac malformations and alteration of TGFbeta signaling system in diabetic
      embryopathy.
AB  - BACKGROUND: Cardiovascular defects are the most common anomalies in diabetic
      embryopathy. The mechanisms underlying the manifestation of the defects remain to
      be addressed. METHODS: Female mice were administered streptozotocin to induce
      diabetes. Embryos from euglycemic (control) and hyperglycemic groups were
      examined for morphological and histological evaluation of malformations. Cell
      proliferation and programmed cell death (apoptosis) were assessed using mitotic
      markers (BrdU and Ki67) and TUNEL assay, respectively. Expression of eight four
      genes in the TGFbeta signaling system was analyzed using real-time RT-PCR.
      RESULTS: Structural abnormalities were observed in the heart and neural tube in
      diabetic groups, with significantly higher malformation rates than in control
      groups. Moreover, malformation rates in the heart were higher than those in the
      neural tube. Cardiac abnormalities including dilated heart tube, smaller
      ventricles, conotruncal stenosis, and abnormal heart looping were seen during
      early morphogenesis prior to cardiac septation [embryonic day (E) 9.5-11.5].
      Histological examinations showed hypoplastic myocardium and endocardial cushions.
      After cardiac septation (E15.5), ventricular septal defects were observed, which
      were manifested in the non-muscular portion of the septum. Significant decreases
      in cell proliferation with no differences in apoptosis were observed in the
      myocardium and endocardial cushions in diabetic compared to control groups.
      Factors in the TGFbeta signaling that regulate heart development were
      downregulated by maternal diabetes. CONCLUSIONS: Maternal diabetes causes
      malformations in the heart of the embryo. The heart is more susceptible to
      maternal diabetic insults than the neural tube. Malformations in the heart prior
      to septation are associated with decreased cell proliferation, but not increased
      apoptosis. The TGFbeta signaling is involved in cardiac malformations in diabetic
      embryopathy.

PMID- 20127829
TI  - Static single channel and multichannel water perfusion pressure profilometry in a
      bench model of a urethra.
AB  - AIMS: To determine the catheter perfusion and withdrawal rate which generate the
      most repeatable single (SCPP) and multichannel pressure profilometry (MCPP)
      profiles in a bench model. METHODS: A bench model using a urethral substitute was
      developed in which SCPP and MCPP were performed using the Brown-Wickham method.
      One single channel and four multichannel catheters were tested using seven
      withdrawal rates and three perfusion rates. Repeatability was determined using
      spread of mean profile pressure, cross-correlation, Bland-Altman statistic, and a
      one-tailed Student's t-statistic. An artificial urinary sphincter (AUS) model was
      constructed to create a predictable intraluminal profile. MCPP data were used to
      generate three-dimensional (3D) images of the pressures exerted by the AUS model.
      RESULTS: A withdrawal rate of 0.5 mm/sec and perfusion rate 1 ml/min produced the
      most repeatable SCPP profiles with a spread of mean profile pressure <=7 cmH(2)O.
      For MCPP, a 10 F 6-channel catheter using a withdrawal rate of 1 mm/sec and
      perfusion rate of 1 ml/min produced the most similar profiles (cross-correlation
      = 0.99). However, the spread of MCPP was large (spread <=44 cmH(2)O per channel).
      Nevertheless MCPP was able to consistently demonstrate areas of high pressure as
      predicted by the AUS model. CONCLUSIONS: MCPP was not repeatable and is an
      unreliable measure of urethral pressure. MCPP and 3D images do demonstrate
      directional differences predicted from the AUS model. These may be of use for
      qualitative understanding and appreciation of relative relationships if not
      actual forces within the urethra and have application in understanding urethral
      function in vivo.

PMID- 20127830
TI  - High power-pulsed Nd:YAG laser as a new stimulus to induce BMP-2 expression in
      MC3T3-E1 osteoblasts.
AB  - BACKGROUND AND OBJECTIVE: High-power laser has recently become a physical
      stimulus for bone regeneration. Little is known about how high-power laser
      irradiation affects osteoblast differentiation. This study investigated
      osteoblast responses to high-power laser and combined irradiation with BMP-2
      treatment. STUDY DESIGN/MATERIALS AND METHODS: MC3T3-E1 pre-osteoblasts were
      exposed to laser irradiation, 100 ng/ml BMP-2 or both. Cells were irradiated with
      a Q-switched, pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, with
      a 1,064 nm wavelength and 0.75 W output power under 1.5, 3, or 5 J/cm(2) energy
      densities. Cell proliferation was evaluated using tetrazolium salt, WST-8. To
      determine the effect of these treatments on in vitro osteogenesis, we examined
      alkaline phosphatase (ALP) activity, mineral deposition, and expression of genes
      associated with osteogenesis. Quantitative real time PCR or ELISA was used to
      examine cytokine expression. In each experiment, either non-irradiated or BMP-2
      (100 ng/ml)-treated cells were used as controls. RESULTS: High-power, low-level,
      Nd:YAG laser irradiation significantly increased ALP activity, when combined with
      BMP-2 or not. Cell proliferation declined in the irradiation and combined
      irradiation/BMP-2 groups. Interestingly, Nd:YAG laser stimulation resulted in
      significant induction of endogenous BMP-2 protein and gene expression. The
      increased expression of upstream regulators cbfa1 by Nd:YAG laser alone was
      comparable to exogenous BMP-2 treatment (100 ng/ml). Combined laser/BMP-2
      treatment was synergistic in the expression of some genes (IGF-1, cbfa1) and ALP
      activity, compared to both BMP-2 treatment and laser irradiation alone. In vitro
      matrix mineralization was significantly accelerated by laser stimulation compared
      to that of the control, more so than with the combined laser/BMP-2 treatment.
      CONCLUSIONS: The present in vitro findings demonstrate that high-power, low-level
      Nd:YAG laser increased osteoblast activity, very efficiently accelerating mineral
      deposition. Osteoinductive effect of laser is likely mediated by activation of
      BMP-2-related signaling pathway.

PMID- 20127833
TI  - Continuous uroflow cystometry in the urethane-anesthetized mouse.
AB  - PURPOSE: In vivo animal cystometry represents an accepted methodology for the
      study of lower urinary tract physiology. A particular advantage of the mouse
      model is the availability of genetically modified strains, offering the
      possibility of linking individual genes to relevant physiological events.
      However, small voided volumes complicate the ability to obtain reliable pressure
      flow data by gravimetric methods, due to non-continuous drop formation and
      release during voiding. We investigated the feasibility of a simple non
      gravimetric continuous urine collection system during cystometry under urethane
      anesthesia, and compared urethane-anesthetized with awake cystometry. METHODS:
      Cystometry was performed in awake and urethane-anesthetized female mice using a
      suprapubic tube. A simple, novel non-gravimetric method of urine collection was
      used in urethane-anesthetized animals to assess voided volume and permit flow
      rate calculations. Pressure and time-related variables were compared between
      groups. RESULTS: Voided urine collection appears to be complete and continuous in
      this model. Mean voided volume was 0.09 +/- 0.020 ml, with an average flow rate
      of 0.029 +/- 0.007 ml/sec. Urethane anesthesia delayed cystometric
      pressure/volume responses. However, micturition reflexes were intact and
      otherwise comparable between groups. Female mice void with pulsatile
      pressurization previously described in rats. CONCLUSION: Suprapubic voiding
      cystometry using a simple and reliable urine collection method under urethane
      anesthesia is feasible in mice, permitting the integration of voided volumes with
      pressure and time data. The inclusion of volume and flow data enhances the
      usefulness of the mouse model for in vivo assessment of detrusor and potentially
      sphincteric performance.

PMID- 20127832
TI  - Urodynamics, the supine empty bladder stress test, and incontinence severity.
AB  - AIMS: Determine whether urodynamic measures of urethral function [(valsalva leak
      point pressure (VLPP), maximum urethral closure pressure (MUCP), functional
      urethral length (FUL)] and the results of the supine empty bladder stress test
      (SEBST) correlate with each other and with subjective and objective measures of
      urinary incontinence (UI). METHODS: Data were collected preoperatively from
      subjects enrolled in a multicenter surgical trial of mid-urethral slings.
      Subjective measures included questionnaire scores from the Medical
      Epidemiological and Social Aspects of Aging Questionnaire, Urogenital Distress
      Inventory, and Incontinence Impact Questionnaire. Objective measures included a
      24-hr pad weight test, incontinence episode frequency on a 3-day voiding diary,
      and a SEBST. RESULTS: Five hundred ninety-seven women enrolled. Three hundred
      seventy-two women had valid VLPP values; 539 had valid MUCP/FUL values.
      Subjective measures of severity had weak to moderate correlation with each other
      (r = 0.25-0.43) and with objective measures of severity (r = -0.06 to 0.45). VLPP
      and MUCP had moderate correlation with each other (r = 0.36,  P< 0.001).
      Urodynamic measures of urethral function had little or no correlation with
      subjective or objective measures of severity. Subjects with a positive SEBST had
      more subjective and objective severity measures compared to the negative SEBST
      group, but they did not have significantly different VLPP and MUCP values.
      CONCLUSIONS: VLPP and MUCP have moderate correlation with each other, but each
      had little or no correlation with subjective or objective measures of severity or
      with the results of the SEBST. This data suggests that the urodynamic measures of
      urethral function are not related to subjective or objective measures of UI
      severity.

PMID- 20127834
TI  - A new urinary catheter-related quality of life instrument for adults.
AB  - AIMS: To develop and assess the measurement properties of a catheter-related
      quality of life (C-IQoL) instrument designed to support research with persons
      using long-term urinary catheter users who use indwelling urethral or suprapubic
      catheters permanently. METHODS: Testing was conducted in two small studies for
      psychometric qualities of reliability (internal consistency and test-retest) and
      factor analysis. The initial instrument, which was modified after each study, was
      based on an International Continence Society (ICS) validated generic incontinence
      quality of life tool. ICS guidelines were used to develop content, including
      using descriptive and qualitative literature as well as and subjective/objective
      measures. Literature included content areas related to sexuality, embarrassment,
      and everyday catheter management. RESULTS: A three-factor solution of subscales
      (management, interpersonal, and psychosocial) was created. The final instrument
      contains 22 items. Reliabilities were all satisfactory. CONCLUSIONS: Quality of
      life continence instruments need to be device-specific to address appropriate and
      critical issues in randomized trials. For further development of a valid and
      reliable measure, continued collaboration is needed among researchers working
      with this population.

PMID- 20127835
TI  - Ultrasound measurement of bladder wall thickness is associated with the
      overactive bladder syndrome.
AB  - AIMS: To assess the relationship between mean bladder wall thickness and
      components of the overactive bladder (OAB syndrome). METHODS: Women attending
      urogynaecology clinic was categorized into overactive bladder syndrome, stress
      urinary incontinence (SUI), and mixed urinary continence (MUI) according to
      International Continence Society (ICS) definitions based on symptom history.
      Women completed a bladder diary, visual analog score (VAS) for urgency, and the
      mean bladder wall thickness (BWT) was determined. Comparison was made between the
      mean BWT and symptom history, daytime frequency, nocturia, VAS scores. RESULTS:
      Three hundred seventy-nine women were recruited to the study with a mean age of
      56 years (range: 24-92 years). The mean bladder wall thickness did not show any
      age-related difference. Of these women 138/379 (36%) reported overactive bladder
      symptoms (mean BWT = 5.6 mm) 75/379 (20%) gave a history of stress urinary
      incontinence (mean BWT = 4.7 mm), and 166/379 (44%) had mixed urinary
      incontinence (mean BWT = 5.4). Women with nocturia >1 had mean BWT 5.6 mm, with
      nocturia <1 a mean BWT 4.9 mm. Women with daytime frequency >7 had mean BWT 5.7
      mm and those <7 had mean BWT 5.1 (P < 0.001). Women with a mean BWT of <=5 mm had
      a mean VAS score lower than women with a BWT >5 mm (P < 0.001). CONCLUSIONS: Mean
      BWT is associated with a symptom history of OAB and MUI, higher daytime and
      nightime frequency, and higher VAS scores.

PMID- 20127836
TI  - Antagonism of macrophage migration inhibitory factor decreases cyclophosphamide
      cystitis in mice.
AB  - AIMS: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine
      found pre-formed in the urothelium. During inflammation, MIF is released into the
      bladder lumen and bladder MIF mRNA is upregulated. Since MIF also has tautomerase
      activity and blocking tautomerase activity also blocks MIF's biological activity,
      we hypothesized that blocking MIF's tautomerase activity would prevent bladder
      inflammation. Therefore, we examined the effects of a MIF tautomerase inhibitor
      (ISO-1; also blocks biological activity) on cyclophosphamide (CYP)-induced
      cystitis in mice. METHODS: Mice receiving CYP (300 mg/kg; i.p.) to induce
      cystitis or saline (control) were treated either with ISO-1 (20 mg/kg; i.p.;
      daily) or vehicle (20% DMSO; i.p.; daily) for 2 days. After 2 days, micturition
      volume and frequency in awake mice were recorded and also mechanical sensitivity
      to abdominal stimulation using von Frey monofilaments. Bladders were collected
      under anesthesia and examined histologically, nerve growth factor levels were
      assayed in bladder homogenates, and production of inflammatory cytokines in the
      bladder was determined using a targeted array. RESULTS: CYP treatment resulted in
      decreased micturition volume, increased frequency, decreased threshold, increased
      histological signs of cystitis, increased bladder NGF levels and production of
      inflammatory cytokines when compared to the control group. Treatment with ISO-1
      prevented or greatly decreased all these changes. CONCLUSION: Antagonizing MIF's
      activity with a systemic MIF tautomerase inhibitor was able to prevent or greatly
      reduced chemical cystitis in mice, thus indicating the MIF mediates bladder
      inflammation in this model. MIF represents a novel and important modulator of
      cystitis.

PMID- 20127837
TI  - A re-adjustable sling for female recurrent stress incontinence and sphincteric
      deficiency: Outcomes and complications in 125 patients using the Remeex sling
      system.
AB  - AIMS: To evaluate the outcomes, complications, and quality of life of patients
      after a Remeex re-adjustable sling for recurrent stress urinary incontinence
      (SUI) and intrinsic sphincteric deficiency (ISD) indications. METHODS: One
      hundred twenty-five patients with SUI were prospectively evaluated following a re
      adjustable sling in a single tertiary academic Center. Patients were classified
      by Q-tip, urodynamic and clinical criteria into ISD (70) and recurrent SUI (55).
      All patients underwent a re-adjustable sling placement. Outcome measures included
      pad-test, urodynamics, and the King's Health Questionnaire. RESULTS: After a mean
      follow-up of 38 months (26-72), 109 patients (87%) are cured of SUI based on pad
      test, clinical, and urodynamic criteria. Sixteen patients (13%) remain
      incontinent. Nine of those (7%) are satisfied to the point that they decline re
      adjustment of the sling, and seven (6%) are on the waiting list for re
      adjustment. Nineteen patients show urge incontinence (9 with previous urodynamic
      mixed incontinence, 10 (8%) with de novo detrusor overactivity). Twenty-one
      patients benefited from a re-adjustment of the sling during the follow-up. The
      tension was increased in 17 cases (continent at discharge) due to recurrence of
      SUI, and reduced in 4 due to obstruction. The Varitensor was removed in 1 case
      due to infection. No other complications were seen. CONCLUSIONS: The Remeex re
      adjustable sling system provides a good cure rate for recurrent SUI and ISD with
      a low complication rate. The ability to increase or decrease sling tension
      allowed us to achieve cure in patients who were not initially dry, and to relieve
      obstruction in every case attempted.

PMID- 20127838
TI  - Predictive value of the ischemic stroke lesion to detrusor function.

PMID- 20127839
TI  - Self-report of difficult defecation is associated with overactive bladder
      symptoms.
AB  - AIMS: The association of dysfunctional bowel elimination with lower urinary tract
      symptoms is well known in children, but not in adults. It was our objective to
      assess lower urinary tract symptoms (LUTS) in women who report difficult
      defecation (DD). METHODS: This is a secondary analysis of 2,812 women, aged 35
      64, who participated in a telephone interview. All subjects were asked "When you
      move your bowels, does the stool come out easily?" DD was considered present in
      those answering "no." All subjects were queried regarding LUTS, urinary
      infections in the past year, self-perceived health status, medical history, and
      demographics. Symptoms of stress incontinence (five items), urge incontinence
      (five items), and the impact of these symptoms on their quality of life were
      solicited from subjects reporting more than 12 episodes of incontinence in 1
      year. RESULTS: DD was reported by 10.4% (290/2,790) of women. Women with DD had
      higher LUTS than those who did not: nocturia (mean 1.8 +/- 0.1 vs. 1.3 +/- 0.0),
      urgency (47.6% vs. 29.2%), increased daytime frequency (mean 8.2 +/- 0.3 vs. 7.2
      +/- 0.1), dysuria (22.9% vs. 13.7%), and a sensation of incomplete bladder
      emptying (55.6% vs. 28.2%). DD women were more often menopausal, reported a fair
      or poor self-reported health status, and had a higher number of comorbidities,
      less formal education, and lower annual household income. CONCLUSIONS: Women with
      symptoms of DD have an increased rate of LUTS, consistent with the diagnosis of
      overactive bladder without incontinence. The pathophysiology underlying this
      association is worthy of future research.

PMID- 20127840
TI  - The effects of chronic hyperlipidemia on bladder function in myocardial
      infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits.
AB  - AIMS: Lower urinary tract symptoms (LUTS) are common in the aging population.
      LUTS cause profoundly negative impacts on their quality of life. Pathophysiology
      of LUTS is multifactorial, and recently, bladder ischemia and metabolic syndrome
      have been suggested as etiological factors. To evaluate chronic hyperlipidemia on
      bladder function, we examined the functional and histological changes of the
      bladder in myocardial infarction-prone Watanabe Heritable Hyperlipidemic (WHHLMI)
      rabbits. METHODS: 20- to 24-month-old WHHLMI rabbits and age- and sex-matched
      control rabbits were prepared. Bladder functions were evaluated using
      cystometrograms and functional experiments with isolated bladder specimens.
      Histological studies of bladder and internal iliac arteries were performed with
      hematoxylin and eosin staining. The bladder was also stained
      immunohistochemically with mouse monoclonal S-100 antibodies and sheep polyclonal
      calcitonin gene-related peptide (CGRP) antibodies. RESULTS: In cystometric
      examination, WHHLMI rabbits showed significantly shorter micturition interval,
      smaller voided volume with non-voiding contractions, and lower micturition
      pressure, as compared to control. The functional experiments showed that
      carbachol- and electrical field stimulation-induced contractions were
      significantly decreased in WHHLMI rabbits than those in control. In WHHLMI
      rabbits, cross-sections of internal iliac arteries showed significant
      atherosclerosis and thickening of media. Bladder showed thinner urothelium and
      decreased smooth muscle area in WHHLMI rabbits, as compared to control. WHHLMI
      rabbits showed a significant decrease in S-100 protein positive neurons, and an
      increased number of CGRP positive neurons. CONCLUSIONS: This study demonstrated
      that WHHLMI rabbits showed detrusor overactivity with decreased detrusor
      contraction. It is suggested that chronic hyperlipidemia contributes to the
      bladder dysfunction.

PMID- 20127841
TI  - Chronic sacral nerve stimulation prevents detrusor structural and functional
      changes associated with bladder outlet obstruction--a rat model.
AB  - AIMS: Bladder outlet obstruction (BOO) can mediate structural and functional
      detrusor changes, which can lead to bothersome lower urinary tract symptoms. We
      investigate if sacral nerve stimulation (SNS) can prevent these structural and
      functional changes in a rat model of BOO. METHODS: 24 female Sprague-Dawley rats
      (250 gm) were divided into 4 groups: control (CTRL), BOO, SNS, and both
      (BOO/SNS). BOO was achieved by partially occluding the proximal urethra. SNS
      involved stimulating the S1-S4 dorsal roots with a unipolar S1 lead, 8 hours
      daily. Urodynamics were performed at baseline and after 6 weeks. Bladders were
      harvested, stained, and scored for detrusor hypertrophy and fibrosis (scale = 1
      5). RESULTS: BOO caused an increase in mean voiding pressure (P(det) = 35 +/- 2
      mmHg vs. 23 +/- 1 mmHg, p = 0.02), an increase in mean bladder capacity (C = 1230
      +/- 250 microl vs. 484 +/- 60 microl, p = 0.03), and a decrease in mean volume at
      first non-voiding contraction (67 +/- 16 microl vs. 110 +/- 24 microl, p = 0.02)
      compared to CTRL. Addition of SNS neither significantly affected P(det) (30 +/- 3
      mm Hg vs. 35 +/- 2 mmHg, p = 0.2), nor C (630 +/- 90 microl vs. 1230 +/- 250
      microl, p = 0.06) compared to BOO, but eliminated non-voiding contractions.
      Detrusor hypertrophy and fibrosis were both significantly greater in BOO vs. CTRL
      and vs. BOO/SNS. CONCLUSIONS: Partial BOO caused functional and structural
      changes in the rat bladder. SNS in obstructed rats prevents these alterations,
      without adversely affecting detrusor contractility.

PMID- 20127842
TI  - Assessment of non-neurogenic incontinence and lower urinary tract symptoms in
      adolescents and young adults.
AB  - AIMS: The aim of this article is to provide insight to clinicians who principally
      treat adults, about non-neurogenic lower urinary tract symptoms (LUTS) either pre
      dating or presenting in adolescence. Assessment fundamentals, diagnostic
      classification, and rationale behind the process of care are discussed. METHODS:
      Standardized terms are used to describe the current classification of symptoms of
      LUT dysfunction in young adults. The etiology and symptomatology of continuous
      and organic incontinence, along with the intermittent presentations of
      incontinence, nocturnal enuresis, and bowel dysfunction are presented. Minimally
      acceptable assessment processes are defined. Indications for the inclusion of
      urodynamic investigations are presented. Throughout the review specific needs of
      adolescents, as they apply to clinical management of LUTS, are highlighted.
      RESULTS: Puberty and growth are likely to challenge compensatory mechanisms for a
      safe urinary system in young adults with organic/structural/developmental LUT
      disorders. The priority of care is to screen for and detect precursor signs of
      renal deterioration. In adolescents with non-neurogenic bladder dysfunction a
      clear diagnosis and identification of both incomplete bladder emptying and high
      detrusor pressure will minimize permanent changes to both the upper and lower
      urinary tracts. CONCLUSIONS: The assessment of adolescents with LUTS requires
      time, thoughtful enquiry, and communication. Dysfunction pre-dating young
      adulthood commonly inhibits autonomy, recreational and social activities thus
      impacting on the adolescent's self-esteem and adherence to treatment regimes.

PMID- 20127843
TI  - Mitochondrial DNA patterns in the Iberian Northern plateau: population dynamics
      and substructure of the Zamora province.
AB  - Several studies have shown the importance of recent events in the configuration
      of the genetic landscape of a specific territory. In this context, due to the
      phenomena of repopulation and demographic fluctuations that took place in recent
      centuries, the Iberian Northern plateau is a very interesting case study. The
      main aim of this work is to check if recent population movements together with
      existing boundaries (geographical and administrative) have influenced the current
      genetic composition of the area. To accomplish this general purpose,
      mitochondrial DNA variations of 214 individuals from a population located in the
      Western region of the Iberian Northern plateau (the province of Zamora) were
      analyzed. Results showed a typical Western European mitochondrial DNA haplogroup
      composition. However, unexpected high frequencies of U5, HV0, and L haplogroups
      were found in some regions. The analyses of microdifferentiation showed that
      there are differences between regions, but no geographic substructure
      organization can be noticed. It can be stated that the differences observed in
      the genetic pool of the sampled area at regional level results from the mixture
      of different populations carrying new lineages into this area at different points
      in history.

PMID- 20127844
TI  - An interspecific analysis of relative jaw-joint height in primates.
AB  - Jaw-joint height (JJH) above the occlusal plane is thought to be influenced by
      cranial base angle (CBA) and facial angulation during growth. To better
      understand how JJH relates to midline craniofacial form, we test the hypothesis
      that relative increases in JJH are correlated with increasing CBA flexion and
      facial kyphosis (i.e., ventral bending) across primates. We compared JJH above
      the occlusal plane to CBA and the angle of facial kyphosis (AFK) across adults
      from 82 species. JJH scales with positive allometry relative to a skull geometric
      mean in anthropoids and most likely strepsirrhines. Anthropoid regressions for
      JJH are elevated above strepsirrhines, whereas catarrhines exhibit a higher slope
      than platyrrhines. Semipartial correlations between relative JJH and both CBA and
      AFK show no association across a small strepsirrhine sample, limited associations
      among catarrhines and anthropoids, but strong correlations in platyrrhines.
      Contrary to our hypothesis, however, increases in relative JJH are correlated
      with relatively less flexed basicrania and more airorhynch faces (i.e., reduced
      ventral bending) in platyrrhines. The mosaic pattern of relationships involving
      JJH across primate clades points to multiple influences on JJH across primates.
      In clades showing little association with basicranial and facial angles, such as
      strepsirrhines, the potential morphological independence of JJH may facilitate a
      relative freedom for evolutionary changes related to masticatory function.
      Finally, failure to associate relative JJH and basicranial flexion in most clades
      suggests that the relatively taller JJH and more flexed basicrania of anthropoids
      compared to strepsirrhines may have evolved as an isolated event during the
      origin of anthropoids.

PMID- 20127845
TI  - Radiological appearance of inflammatory myofibroblastic tumour.
AB  - Inflammatory myofibroblastic tumour (IMFT) is a distinct entity with variable
      clinical presentation and therapeutic options. We present three paediatric cases
      of IMFT, originated from the lung, bladder and ovary respectively. All lesions
      were heterogeneous, with mixed solid/cystic components and infiltrative pattern,
      and were interpreted as aggressive malignant neoplasms initially due to their
      bizarre imaging appearance. The definitive diagnosis was derived from
      characteristic histopathological features.

PMID- 20127847
TI  - Use of bisphosphonates for the treatment of osteonecrosis as a complication of
      therapy for childhood acute lymphoblastic leukaemia (ALL).
AB  - BACKGROUND: Osteonecrosis is a well-recognised complication of current childhood
      acute lymphoblastic leukaemia (ALL) therapy. There are few studies on the medical
      management of osteonecrosis in this setting. We studied the therapeutic and
      radiological effects of oral and intravenous bisphosphonate use compared with
      standard care as treatment for osteonecrosis in this population. METHOD: Patients
      who developed osteonecrosis as a complication of ALL therapy between 1994 and
      2007 were treated at a single paediatric institution. Of 17 patients, 9 were
      commenced on bisphosphonates and 8 treated conservatively. Both groups were
      observed with time. Pain, analgesic requirement and musculoskeletal function were
      assessed monthly. Affected joints were radiologically imaged at set intervals.
      Each scan was graded using an ellipsoid method to give the total volume of
      osteonecrosis, by blinded radiologic examination. RESULTS: Three of six patients
      treated with oral alendronate showed clinical improvement. The three patients
      that had no improvement were subsequently treated with intravenous pamidronate.
      All six patients treated with intravenous pamidronate showed clinical
      improvement. Seven of eight conservatively treated patients deteriorated
      clinically. All patients demonstrated reduction in the radiological burden of
      osteonecrosis with time. There was no difference in the rate of reduction between
      conservative and bisphosphonate arms. CONCLUSION: Bisphosphonate use, in
      particular pamidronate, improved pain scores, analgesic requirement and
      musculoskeletal function in patients with osteonecrosis occurring as a
      complication of childhood ALL therapy. Objective radiologic benefit of
      bisphosphonate treatment could not be demonstrated. Risks, benefits and long-term
      outcome of bisphosphonate use in this population should be addressed in a larger
      prospective, randomised trial.

PMID- 20127846
TI  - Toxicity assessment of molecularly targeted drugs incorporated into multiagent
      chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from
      an international consensus conference.
AB  - One of the challenges of incorporating molecularly targeted drugs into multi
      agent chemotherapy (backbone) regimens is defining dose-limiting toxicities
      (DLTs) of the targeted agent against the background of toxicities of the backbone
      regimen. An international panel of 22 pediatric acute lymphocytic leukemia (ALL)
      experts addressed this issue (www.ALLNA.org). Two major questions surrounding DLT
      assessment were explored: (1) how toxicities can be best defined, assessed, and
      attributed; and (2) how effective dosing of new agents incorporated into multi
      agent ALL clinical trials can be safely established in the face of disease- and
      therapy-related systemic toxicities. The consensus DLT definition incorporates
      tolerance of resolving Grade 3 and some resolving Grade 4 toxicities with
      stringent safety monitoring. This functional DLT definition is being tested in
      two Children's Oncology Group (COG) ALL clinical trials.

PMID- 20127848
TI  - Undifferentiated sarcoma of the thyroid in a child.
AB  - The most common malignant tumor of the thyroid is papillary carcinoma. Sarcoma of
      the thyroid is encountered very rarely; its therapy is complex and poses
      significant problems due to the problematic location of the tumor. A 14-year-old
      female was diagnosed with undifferentiated sarcoma of the thyroid and received
      combined therapy comprising surgery, chemo- and radiotherapy without significant
      side effects. This case underlines the fact that undifferentiated thyroid sarcoma
      may be a diagnostic possibility in children with malignant masses of the neck and
      may be successfully treated with modern therapeutic strategies.

PMID- 20127849
TI  - An updated follow-up of chronic hepatitis C after three decades of observation in
      pediatric patients cured of malignancy.
AB  - BACKGROUND: The aim of the study was to evaluate the clinical characteristics and
      the long-term outcome of chronic hepatitis C in a cohort of Caucasian children
      cured of pediatric malignancy. PROCEDURE: The study population included 83
      consecutive patients, referred to our Center with a diagnosis of
      leukemia/lymphoma (50) or solid tumors (33) between 1977 and 1989 and infected
      with hepatitis C virus (HCV) during chemotherapy. RESULTS: At enrollment 77
      subjects were HCV-RNA positive. After a median follow-up of 21 years (range 13
      36), a sustained virological response (SVR) was obtained in 3 of 29 patients
      (10%) treated with interferon (IFN), in 1 of 3 patients (33%) treated with IFN
      and ribavirin, and in 5 of 11 patients (42%) treated with pegylated-IFN and
      ribavirin (P = 0.03). Forty-two patients remained untreated and only one (2.5%)
      cleared viremia. Four of 77 patients (5%) developed cirrhosis while other 4
      patients died of causes not related to liver. At last follow-up, 72% of HCV-RNA
      positive patients had abnormal ALT. CONCLUSIONS: In patients cured of pediatric
      malignancy chronic hepatitis C tends to run an indolent course during childhood
      and adolescence but more than 70% of treated and more than 80% of untreated cases
      children maintained HCV viremia. Moreover, after 2-3 decades of observation, 60%
      of HCV-RNA positive patients had abnormal ALT and 5% had developed cirrhosis.
      Among treated patients, IFN or pegylated-IFN and ribavirin obtained the higher
      rate of HCV-RNA clearance.

PMID- 20127850
TI  - Quality of life in young patients after bone tumor surgery around the knee joint
      and comparison with healthy controls.
AB  - BACKGROUND: This study aimed to compare the health related quality of life
      (HRQoL) of children and adolescents after malignant bone tumor surgery of the leg
      with healthy controls. PROCEDURE: Patients between 8 and 25 years old were cross
      sectional recruited. Patients under 16 years of age received the TNO (Netherlands
      Organization for Applied Scientific Research) and AZL (Leiden University Medical
      Center) Children's Quality of Life Questionnaire (TACQOL), patients aged 16 years
      and older received the TNO-AZL Questionnaire for Adult's Quality of Life (TAAQOL)
      and the Short Form-36 (SF-36). Three age- and sex-matched normative random
      samples, drawn from large, nationwide studies, were used for the comparison with
      healthy controls. Patients were interviewed regarding their most important
      problems related to the disease and its treatment. RESULTS: Eighty-one patients
      with a mean age of 16.9 years (SD 4.2) were included (41 female). Limb sparing
      surgery was executed in 38 patients, ablative surgery in 43 patients. In
      comparison with healthy controls, patients had significantly poorer HRQoL within
      the domains autonomy and motor function of the TACQOL, gross motor function,
      cognitive functioning, daily functioning and sexuality of the TAAQOL, and
      physical functioning, role physical, general health, and the physical and mental
      component summary scales of the SF-36. Patients reported limitations in physical
      activities, participation in sports, and cosmetic aspects as the most detrimental
      consequences of their disease and its treatment. CONCLUSION: In children and
      adolescents who underwent surgery for a malignant tumor of the leg physical,
      functioning was significantly impaired as compared to healthy controls.

PMID- 20127851
TI  - Pleuropulmonary blastoma with intrabronchial extension.
AB  - A 3-year-old male presented with an episode of respiratory distress that was
      superimposed on a 2 1/2 years history of recurrent chest infections. The chest
      radiograph and a contrast enhanced CT scan revealed a cystic cavity in the left
      upper lobe with an endobronchial soft tissue mass in left bronchus. Left
      bronchotomy and removal of the endobronchial soft tissue mass and left upper
      lobectomy were performed. The histology of the specimen revealed a
      pleuropulmonary blastoma (PPB) type II. The presentation, diagnosis, and
      management of this uncommon case of PPB with intrabronchial extension are
      described.

PMID- 20127852
TI  - Score-based adjustment for confounding by population stratification in genetic
      association studies.

PMID- 20127853
TI  - Functional central nervous system myelin repair in an adult mouse model of
      demyelination caused by proteolipid protein overexpression.
AB  - Two types of interventions to remyelinate the adult demyelinated central nervous
      system were investigated in heterozygous transgenic mice overexpressing the
      proteolipid protein gene. 1) A cocktail of trophic factors, "TS1," was directed
      toward the activation of the endogenous pool of neural progenitors to increase
      the number of myelinating oligodendrocytes (OL) in the brain. 2) A combinatorial
      approach in which OL progenitors were coinjected with TS1 into the corpus
      callosum of wild-type and He4e transgenic mice that displayed hindlimb paralysis.
      The levels of locomotor ability in these mice were evaluated after a single
      treatment. The data showed that a single administration of either one of the
      interventions had similar therapeutic effects, alleviating the symptoms of
      demyelination and leading to the recovery of hindlimb function. Histological and
      immunofluorescent examination of brain sections showed extensive remyelination
      that was sufficient to reverse hindlimb paralysis in transgenic mice. When the
      interventions were administered prior to hindlimb paralysis, He4e mice were able
      to walk up to 1 year of age without paralysis.

PMID- 20127854
TI  - Identification of small peptides mimicking the R2 C-terminus of Mycobacterium
      tuberculosis ribonucleotide reductase.
AB  - Ribonucleotide reductase (RNR) is a viable target for new drugs against the
      causative agent of tuberculosis, Mycobacterium tuberculosis. Previous work has
      shown that an N-acetylated heptapeptide based on the C-terminal sequence of the
      smaller RNR subunit can disrupt the formation of the holoenzyme sufficiently to
      inhibit its function. Here the synthesis and binding affinity, evaluated by
      competitive fluorescence polarization, of several truncated and N-protected
      peptides are described. The protected single-amino acid Fmoc-Trp shows binding
      affinity comparable to the N-acetylated heptapeptide, making it an attractive
      candidate for further development of non-peptidic RNR inhibitors.

PMID- 20127855
TI  - Controlling the helical screw sense of peptides with C-terminal L-valine.
AB  - One chiral L-valine (L-Val) was inserted into the C-terminal position of achiral
      peptide segments constructed from alpha-aminoisobutyric acid (Aib) and alpha,beta
      dehydrophenylalanine (Delta(Z)Phe) residues. The IR, (1)H NMR and CD spectra
      indicated that the dominant conformations of the pentapeptide Boc-Aib-DeltaPhe
      (Aib)(2)-L-Val-NH-Bn (3) and the hexapeptide Boc-Aib-DeltaPhe-(Aib)(3)-L-Val-NH
      Bn (4) in solution were both right-handed (P) 3(10)-helical structures. X-ray
      crystallographic analyses of 3 and 4 revealed that only a right-handed (P) 3(10)
      helical structure was present in their crystalline states. The conformation of 4
      was also studied by molecular-mechanics calculations.

PMID- 20127856
TI  - Characterization of X-chromosome inactivation status in human pluripotent stem
      cells.
AB  - This unit describes a method of performing fluorescent in situ hybridization
      (FISH) of XIST and Cot-1 RNA in human pluripotent stem cells (hPSC) to
      characterize the epigenetic status of X-chromosome inactivation (XCI). hPSC
      laboratories commonly practice karyotypic analysis to monitor genetic stability;
      however, epigenetic stability is often overlooked. Several laboratories have
      recently shown that markers of XCI can be used as one effective screen to monitor
      the epigenetic status of hPSCs. Human embryonic stem cells (HESC) fall into three
      classes of XCI states: upregulating XIST upon differentiation, always expressing
      XIST in the undifferentiated and differentiated states, and never expressing XIST
      in the undifferentiated and differentiated states. Failure to express XIST
      represents an especially concerning state in hESC, as this state does not occur
      in healthy female cells but is often seen in malignancies. Herein, methods of
      carrying out XIST RNA and Cot-1 RNA FISH are described. FISH analysis of XIST
      RNA, unlike general expression analysis such as RT-PCR, allows for the
      classification of XCI on a single-cell level, enabling a quantitative
      determination of the degree of epigenetic change across the population. The
      complementary Cot-1 analysis measures the extent of repeat element expression
      throughout the nucleus and therefore enables determination, at a cytological
      level, of the extent to which the X chromosome is silent. Because the different
      steps of XCI are some of the first epigenetic changes to take place in
      differentiating hESC, analysis of the XCI state provides a first indication of an
      hESC culture's overall health.

PMID- 20127857
TI  - A convenient microwave-enhanced solid-phase synthesis of short chain N-methyl
      rich peptides.
AB  - Structural modification of the peptide backbone via N-methylation is a powerful
      tool to modulate the pharmacokinetic profile and biological activity of peptides.
      Here we describe a rapid and highly efficient microwave(MW)-assisted Fmoc/tBu
      solid-phase method to prepare short chain N-methyl-rich peptides, using Rink
      amide p-methylbenzhydrylamine (MBHA) resin as solid-phase support. This method
      produces peptides in high yield and purity, and reduces the time required for
      Fmoc-N-methyl amino acid coupling.

PMID- 20127858
TI  - Kindlin-2 is expressed in malignant mesothelioma and is required for tumor cell
      adhesion and migration.
AB  - Kindlin-2 is a novel integrin-interacting focal adhesion protein that belongs to
      the Kindlin family. Focal adhesion proteins control cytoskeleton dynamics and
      promote cancer cell growth, survival, migration and metastasis. Little is known,
      however, about expression of Kindlin-2 in association with human cancer. We now
      reveal high Kindlin-2 expression in malignant mesothelioma (MM) cell lines using
      an affinity-purified anti-Kindlin-2 antibody. Furthermore, we show by
      immunohistochemistry that Kindlin-2 is highly expressed in 92 of 102 (90%) MMs
      with epitheliod; sarcomatoid, biphasic and poorly differentiated morphologies. In
      addition, Kindlin-2 expression correlates to cell proliferation, suggesting a
      role for Kindlin-2 in tumor growth. We also detect increased expression of
      Kindlin-2 at the invasion front of tumors concurrent with increased expression of
      integrin-linked kinase, a Kindlin-binding protein. Besides the high expression of
      Kindlin-2 in pleural MMs, pleural metastases of lung adenocarcinoma also express
      large amounts of Kindlin-2, but not Kindlin-1. Notably, in vitro, when endogenous
      Kindlin-2 was knocked down with RNAi in MM cells, this impaired cell spreading,
      adhesion and migration. Overall, our study suggests that heightened expression of
      Kindlin-2 might contribute to tumor progression in MM.

PMID- 20127860
TI  - Intraepithelial p63-dependent expression of distinct components of cell adhesion
      complexes in normal esophageal mucosa and squamous cell carcinoma.
AB  - TP63 gene is a member of TP53 tumor suppressor gene family that encodes several
      protein isoforms involved in the process of epithelial stratification and in
      epithelial-mesenchyme interactions. TP63 is amplified in a significant proportion
      of squamous cell carcinoma of the esophagus (ESCC), resulting in the hyper
      expression of DeltaNp63 as the major p63 isoform. To better understand the
      contribution of this high expression to tumorigenesis, we have analyzed the
      impact of intraepithelial p63 expression on the expression of cell adhesion
      complexes in normal esophagus and in ESCC cell lines. Cells expressing p63 showed
      an adhesion pattern characterized by lack of tight junctions and presence of
      adherens junctions. Cell differentiation was accompanied by a decrease in p63 and
      by a shift to adhesion patterns involving tight junctions. Silencing of p63 mRNA
      in ESCC cell lines resulted in a similar shift, characterized by increased
      expression of component of tight junctions, decreased cell-to-cell communication
      and downregulation of cell proliferation. These results indicate that DeltaNp63
      may contribute to esophageal squamous carcinogenesis by maintaining cell adhesion
      patterns compatible with cell proliferation.

PMID- 20127859
TI  - Oral benzo[a]pyrene-induced cancer: two distinct types in different target organs
      depend on the mouse Cyp1 genotype.
AB  - Benzo[a]pyrene (BaP) is a prototypical polycyclic aromatic hydrocarbon (PAH)
      found in combustion processes. Cytochrome P450 1A1 and 1B1 enzymes (CYP1A1 and
      CYP1B1) can both detoxify PAHs and activate them to cancer-causing reactive
      intermediates. Following high dosage of oral BaP (125 mg/kg/day), ablation of the
      mouse Cyp1a1 gene causes immunosuppression and death within ~28 days, whereas
      Cyp1(+/+) wild-type mice remain healthy for >12 months on this regimen. In this
      study, male Cyp1(+/+) wild-type, Cyp1a1(-/-) and Cyp1b1(-/-) single-knockout and
      Cyp1a1/1b1(-/-) double-knockout mice received a lower dose (12.5 mg/kg/day) of
      oral BaP. Tissues from 16 different organs-including proximal small intestine
      (PSI), liver and preputial gland duct (PGD)-were evaluated; microarray cDNA
      expression and >30 mRNA levels were measured. Cyp1a1(-/-) mice revealed markedly
      increased CYP1B1 mRNA levels in the PSI, and between 8 and 12 weeks developed
      unique PSI adenomas and adenocarcinomas. Cyp1a1/1b1(-/-) mice showed no PSI
      tumors but instead developed squamous cell carcinoma of the PGD. Cyp1(+/+) and
      Cyp1b1(-/-) mice remained healthy with no remarkable abnormalities in any tissue
      examined. PSI adenocarcinomas exhibited striking upregulation of the Xist gene,
      suggesting epigenetic silencing of specific genes on the Y-chromosome; the Rab30
      oncogene was upregulated; the Nr0b2 tumor suppressor gene was downregulated;
      paradoxical overexpression of numerous immunoglobulin kappa- and heavy-chain
      variable genes was found-although the adenocarcinoma showed no
      immunohistochemical evidence of being lymphatic in origin. This oral BaP mouse
      paradigm represents an example of "gene-environment interactions" in which the
      same exposure of carcinogen results in altered target organ and tumor type, as a
      function of just 1 or 2 globally absent genes.

PMID- 20127861
TI  - CCR9 mediates PI3K/AKT-dependent antiapoptotic signals in prostate cancer cells
      and inhibition of CCR9-CCL25 interaction enhances the cytotoxic effects of
      etoposide.
AB  - Despite recent advances in treatment and management of prostate cancer (PCa), it
      remains the second leading cause of cancer-related deaths among men in the US.
      Chemotherapy is one of the treatment alternatives for hormone refractory
      metastatic PCa. However, current chemotherapeutic regimens provide palliative
      benefit but relatively modest survival advantage primarily due to chemo
      resistance and upregulated antiapoptotic machineries in PCa cells. Therefore,
      blocking the mechanisms responsible for suppression of apoptosis might improve
      current chemotherapeutic regimens. In this study, we show that CC chemokine
      receptor-9 (CCR9) and its natural ligand CCL25 interaction upregulates
      antiapoptotic proteins (i.e., PI3K, AKT, ERK1/2 and GSK-3beta) and downregulate
      activation of caspase-3 in PCa cells. Significant downregulation of these CCR9
      mediated antiapoptotic proteins in the presence of a PI3K inhibitor (wortmannin),
      further suggests that the antiapoptotic action of CCR9 is primarily regulated
      through PI3K. Furthermore, the cytotoxic effect of etoposide was significantly
      inhibited in the presence of CCL25, and this inhibitory effect of CCL25 was
      abrogated when CCR9-CCL25 interaction was blocked using anti-CCR9 monoclonal
      antibodies. In conformation to these in vitro studies, significant reduction in
      tumor burden was found in mice receiving CCL25 neutralizing antibodies and
      etoposide together as compared to both as a single agent. These results suggest
      that the CCR9-CCL25 axis mediates PI3K/AKT-dependent antiapoptotic signals in PCa
      cells and could be a possible reason for low apoptosis and modest
      chemotherapeutic response. Therefore, targeting CCR9-CCL25 axis with cytotoxic
      agents may provide better therapeutic outcomes than using cytotoxic agents alone.

PMID- 20127862
TI  - Activity of deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell
      lymphoma models: Defining molecular mechanisms of resistance.
AB  - Panobinostat (LBH589) is a highly potent deacetylase inhibitor that has
      demonstrated clinical efficacy in patients with advanced cutaneous T-cell
      lymphoma (CTCL). To gain a better understanding of the compound activity in this
      tumor type, we investigated the cellular and molecular effects of panobinostat
      using both in vitro and in vivo models of CTCL. All 4 tested CTCL cell lines
      exhibited very high sensitivity to panobinostat-induced growth inhibition.
      However, only 2 of 4 lines exhibited significant response to the cytotoxic
      activity of panobinostat. In a CTCL xenograft mouse tumor model, panobinostat
      treatment resulted in complete tumor regression. The difference in cell
      sensitivity to panobinostat-induced death enabled us to further investigate
      potential mechanisms responsible for tumor sensitivity or resistance. In CTCL
      cell lines that were insensitive to panobinostat-induced apoptosis,
      constitutively activated NF-kappaB and high levels of Bcl-2 were observed.
      Inhibition of Bcl-2 sensitized cells to the cytotoxic activity of panobinostat.
      Conversely, knockdown of Bax diminished the CTCL cell sensitivity. Interestingly,
      panobinostat could induce cytotoxicity in vorinostat-resistant CTCL cells by
      downregulating phosphorylated STAT3 and STAT5 proteins. These studies suggest
      distinct mechanisms responsible for resistance to different deacetylase
      inhibitors. We show that the intrinsic apoptotic signaling plays an essential
      role in mediating panobinostat anticancer activity. Moreover, cancer cell
      sensitivity to panobinostat treatment may be further improved by combination with
      inhibition of anti-apoptotic factors. These data provide preclinical support that
      panobinostat, as a single agent or in combination with other anticancer agents,
      is a promising therapy for CTCL.

PMID- 20127863
TI  - Curcumin upregulates insulin-like growth factor binding protein-5 (IGFBP-5) and
      C/EBPalpha during oral cancer suppression.
AB  - Curcumin is a common food ingredient derived from the plant Curcuma longa and is
      a potent drug against tumorigenesis. Both insulin-like growth factor binding
      protein-5 (IGFBP-5) and CCAAT/enhancer-binding protein alpha (C/EBPalpha) are
      suppressors of head and neck carcinogenesis. We identified curcumin as an inducer
      of IGFBP-5 expression in multiple types of oral keratinocytes; furthermore,
      curcumin induces IGFBP-5 promoter activity in SAS oral cancer cells. Promoter
      deletion mapping identified a region (nt -71 to nt -59 relative to the
      transcription start site) as containing a C/EBPalpha-binding element that is
      indispensable for curcumin-mediated IGFBP-5 upregulation. Chromatin
      immunoprecipitation assays revealed that in vivo binding of C/EBPalpha to this
      region was remarkably increased in the presence of curcumin. Curcumin increased
      nuclear C/EBPalpha expression and IGFBP-5 expression through p38 activation and
      this was abrogated by SB203580 treatment. Furthermore, MKK6 expression activated
      p38 and C/EBPalpha, increasing IGFBP-5 promoter activity and expression. Finally,
      curcumin-induced IGFBP-5 expression is associated with the suppression of
      xenograft tumorigenesis in mice due to oral cancer cells. We conclude that
      curcumin activates p38, which, in turn, activates the C/EBPalpha transactivator
      by interacting with binding elements in the IGFBP-5 promoter. The consequential
      upregulation of C/EBPalpha and IGFBP-5 by curcumin is crucial to the suppression
      of oral carcinogenesis.

PMID- 20127864
TI  - Investigation of a plasmid containing a novel immunotoxin VEGF165-PE38 gene for
      antiangiogenic therapy in a malignant glioma model.
AB  - Inhibition of tumor neovascularization has profound effects on the growth of
      solid tumors. Our previous studies have shown the effect of VEGF165-PE38
      recombinant immunotoxin on proliferation and apoptosis in human umbilical vein
      endothelial cells in vitro. In this study, we explored the direct inhibition of
      angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a
      malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38-IRES2
      EGFP plasmid. ELISA was used to confirm the expression of VEGF165-PE38 in the
      transfected cells. These cells released 1396 + or - 131.9 pg VEGF165-PE38/1x10(4)
      cells/48 h into the culture medium and the supernatant was capable of inhibiting
      the growth of capillary-like structures in chick chorioallantoic membrane assay.
      In a murine malignant glioma model, plasmid was directly administered via
      multiple local intratumoral delivery. After day 16 the tumor volume in mice
      treated with pVEGF165PE38-IRES2-EGFP was significantly lower than that in mice in
      the control groups. Immunohistochemistry studies showed that the treated group
      had decreased expression of CD31. Quantitative analysis of microvessel density in
      the treated group was 1.99 + or - 0.69/0.74 mm(2), and was significantly lower
      than that in the control groups (9.33 + or - 1.99/0.74 mm(2), 8.09 + or -
      1.39/0.74 mm(2) and 8.49 + or - 1.69/0.74 mm(2)). Immunohistochemistry analysis
      indicated that immunotoxin VEGF165-PE38 was distributed in the treated group in
      malignant glioma tissue. Our findings provide evidence that the in vivo
      production of VEGF165-PE38 through gene therapy using a eukaryotic expression
      plasmid had potential antiangiogenic activity in malignant glioma in vivo.

PMID- 20127865
TI  - Field leaching of pesticides at five test sites in Hawaii: study description and
      results.
AB  - BACKGROUND: Following the discovery of pesticides in wells, the Hawaii Department
      of Agriculture (HDOA) supported research to evaluate the likelihood of pesticide
      leaching to the groundwater in Hawaii. The aim of this study was to evaluate the
      relative leaching pattern of five pesticides at five different sites on three
      islands and to compare their leaching behavior with bromide and a reference
      chemical (atrazine) that is known to leach in Hawaiian conditions. Laboratory
      measurements of sorption and degradation of the pesticides were made. RESULTS:
      Most of the applied mass of pesticides was still present in the top 80 cm after
      the 16 week study period. The aggregated oxisol at Kunia showed the most
      intensive leaching among the five sites. The revised attenuation factor screening
      approach used by the HDOA indicated that all chemicals, with the exception of
      trifloxystrobin, had the potential to leach. Similarly, the groundwater ubiquity
      score ranked trifloxystrobin as a non-leacher. The field leaching data, however,
      suggested that trifloxystrobin was the most mobile compound among the pesticides
      tested. CONCLUSION: Although the results were variable among the sites, the field
      and laboratory experiments provided useful information for regulating use of
      these pesticides in Hawaii.

PMID- 20127866
TI  - A web-based decision support system to enhance IPM programs in Washington tree
      fruit.
AB  - BACKGROUND: Integrated pest management (IPM) decision-making has become more
      information intensive in Washington State tree crops in response to changes in
      pesticide availability, the development of new control tactics (such as mating
      disruption) and the development of new information on pest and natural enemy
      biology. The time-sensitive nature of the information means that growers must
      have constant access to a single source of verified information to guide
      management decisions. RESULTS: The authors developed a decision support system
      for Washington tree fruit growers that integrates environmental data [140
      Washington State University (WSU) stations plus weather forecasts from NOAA],
      model predictions (ten insects, four diseases and a horticultural model),
      management recommendations triggered by model status and a pesticide database
      that provides information on non-target impacts on other pests and natural
      enemies. A user survey in 2008 found that the user base was providing
      recommendations for most of the orchards and acreage in the state, and that users
      estimated the value at $ 16 million per year. CONCLUSIONS: The design of the
      system facilitates education on a range of time-sensitive topics and will make it
      possible easily to incorporate other models, new management recommendations or
      information from new sensors as they are developed.

PMID- 20127867
TI  - Agronomic and environmental implications of enhanced s-triazine degradation.
AB  - Novel catabolic pathways enabling rapid detoxification of s-triazine herbicides
      have been elucidated and detected at a growing number of locations. The genes
      responsible for s-triazine mineralization, i.e. atzABCDEF and trzNDF, occur in at
      least four bacterial phyla and are implicated in the development of enhanced
      degradation in agricultural soils from all continents except Antarctica. Enhanced
      degradation occurs in at least nine crops and six crop rotation systems that rely
      on s-triazine herbicides for weed control, and, with the exception of acidic soil
      conditions and s-triazine application frequency, adaptation of the microbial
      population is independent of soil physiochemical properties and cultural
      management practices. From an agronomic perspective, residual weed control could
      be reduced tenfold in s-triazine-adapted relative to non-adapted soils. From an
      environmental standpoint, the off-site loss of total s-triazine residues could be
      overestimated 13-fold in adapted soils if altered persistence estimates and
      metabolic pathways are not reflected in fate and transport models. Empirical
      models requiring soil pH and s-triazine use history as input parameters predict
      atrazine persistence more accurately than historical estimates, thereby allowing
      practitioners to adjust weed control strategies and model input values when
      warranted.

PMID- 20127868
TI  - Effects of acute psychosocial stress on working memory related brain activity in
      men.
AB  - Acute psychosocial stress in humans triggers the release of glucocorticoids (GCs)
      and influences performance in declarative and working memory (WM) tasks. These
      memory systems rely on the hippocampus and prefrontal cortex (PFC), where GC
      binding receptors are present. Previous studies revealed contradictory results
      regarding effects of acute stress on WM-related brain activity. We combined
      functional magnetic resonance imaging with a standardized psychosocial stress
      protocol to investigate the effects of acute mental stress on brain activity
      during encoding, maintenance, and retrieval of WM. Participants (41 healthy young
      men) underwent either a stress or a control procedure before performing a WM
      task. Stress increased salivary cortisol levels and tended to increase WM
      accuracy. Neurally, stress-induced increases in cortical activity were evident in
      PFC and posterior parietal cortex (PPC) during WM maintenance. Furthermore,
      hippocampal activity was modulated by stress during encoding and retrieval with
      increases in the right anterior hippocampus during WM encoding and decreases in
      the left posterior hippocampus during retrieval. Our study demonstrates that
      stress increases activity in PFC and PPC specifically during maintenance of items
      in WM, whereas effects on hippocampal activity are restricted to encoding and
      retrieval. The finding that psychosocial stress can increase and decrease
      activity in two different hippocampal areas may be relevant for understanding the
      often-reported phase-dependent opposing behavioral effects of stress on long-term
      memory.

PMID- 20127870
TI  - Event-related potential and functional MRI measures of face-selectivity are
      highly correlated: a simultaneous ERP-fMRI investigation.
AB  - A face-selective neural signal is reliably found in humans with functional MRI
      and event-related potential (ERP) measures, which provide complementary
      information about the spatial and temporal properties of the neural response.
      However, because most neuroimaging studies so far have studied ERP and fMRI face
      selective markers separately, the relationship between them is still unknown.
      Here we simultaneously recorded fMRI and ERP responses to faces and chairs to
      examine the correlations across subjects between the magnitudes of fMRI and ERP
      face-selectivity measures. Findings show that the face-selective responses in the
      temporal lobe (i.e., fusiform gyrus--FFA) and superior temporal sulcus (fSTS),
      but not the face-selective response in the occipital cortex (OFA), were highly
      correlated with the face-selective N170 component. In contrast, the OFA was
      correlated with earlier ERPs at about 110 ms after stimulus-onset. Importantly,
      these correlations reveal a temporal dissociation between the face-selective area
      in the occipital lobe and face-selective areas in the temporal lobe. Despite the
      very different time-scale of the fMRI and EEG signals, our data show that a
      correlation analysis across subjects may be informative with respect to the
      latency in which different brain regions process information.

PMID- 20127869
TI  - Emotional imagery: assessing pleasure and arousal in the brain's reward
      circuitry.
AB  - Research on emotional perception and learning indicates appetitive cues engage
      nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), whereas amygdala
      activity is modulated by the emotional intensity of appetitive and aversive cues.
      This study sought to determine patterns of functional activation and connectivity
      among these regions during narrative emotional imagery. Using event-related fMRI,
      we investigate activation of these structures when participants vividly imagine
      pleasant, neutral, and unpleasant scenes. Results indicate that pleasant imagery
      selectively activates NAc and mPFC, whereas amygdala activation was enhanced
      during both pleasant and unpleasant imagery. NAc and mPFC activity were each
      correlated with the rated pleasure of the imagined scenes, while amygdala
      activity was correlated with rated emotional arousal. Functional connectivity of
      NAc and mPFC was evident throughout imagery, regardless of hedonic content, while
      correlated activation of the amygdala with NAc and mPFC was specific to imagining
      pleasant scenes. These findings provide strong evidence that pleasurable text
      driven imagery engages a core appetitive circuit, including NAc, mPFC, and the
      amygdala.

PMID- 20127871
TI  - Attachment style, affective loss and gray matter volume: a voxel-based
      morphometry study.
AB  - Early patterns of infant attachment have been shown to be an important influence
      on adult social behavior. Animal studies suggest that patterns of early
      attachment influence brain development, contributing to permanent alterations in
      neural structure; however, there are no previous studies investigating whether
      differences in attachment style are associated with differences in brain
      structure in humans. In this study, we used Magnetic Resonance Imaging (MRI) and
      voxel-based morphometry (VBM) to examine for the first time the association
      between attachment style, affective loss (for example, death of a loved one) and
      gray matter volume in a healthy sample of adults (n = 32). Attachment style was
      assessed on two dimensions (anxious and avoidant) using the ECR-Revised
      questionnaire. High attachment-related anxiety was associated with decreased gray
      matter in the anterior temporal pole and increased gray matter in the left
      lateral orbital gyrus. A greater number of affective losses was associated with
      increased gray matter volume in the cerebellum; in this region, however, the
      impact of affective losses was significantly moderated by the level of attachment
      related avoidance. These findings indicate that differences in attachment style
      are associated with differences in the neural structure of regions implicated in
      emotion regulation. It is hypothesized that early attachment experience may
      contribute to structural brain differences associated with attachment style in
      adulthood; furthermore, these findings point to a neuronal mechanism through
      which attachment style may mediate individual differences in responses to
      affective loss.

PMID- 20127872
TI  - Independent component analysis of erroneous and correct responses suggests online
      response control.
AB  - After errors in reaction tasks, a sharp negative wave emerges in the event
      related potential (ERP), the error (related) negativity (Ne or ERN). However,
      also after correct trials, an Ne-like wave is seen, called CRN or Nc, which is
      much smaller than the Ne. This study tested the hypothesis whether Ne and Nc
      reflect the same functional process, and whether this process is linked to online
      response control. For this purpose, independent component analysis (ICA) was
      utilized with the EEG data of two types of reaction tasks: a flanker task and a
      mental rotation task. To control for speed-accuracy effects, speed and accuracy
      instructions were balanced in a between subjects design. For both tasks ICA and
      dipole analysis revealed one component (Ne-IC) explaining most of the variance
      for the difference between correct and erroneous trials. The Ne-IC showed
      virtually the same features as the raw postresponse ERP, being larger for
      erroneous compared to correct trials and for the flanker than for the rotation
      task. In addition, it peaked earlier for corrected than for uncorrected errors.
      The results favor the hypothesis that Ne and Nc reflect the same process, which
      is modulated by response correctness and type of task. On the basis of the
      literature and the present results, we assume that this process induces online
      response control, which is much stronger in error than correct trials and with
      direct rather than indirect stimulus response mapping.

PMID- 20127873
TI  - Individual differences in socioaffective skills influence the neural bases of
      fear processing: the case of alexithymia.
AB  - Being exposed to fear signals makes us feel threatened and prompts us to prepare
      an adaptive response. In our previous studies, we suggested that amygdala (AMG)
      and premotor cortex (PM) play a role in the preparation of the observers' motor
      response required by the situation. The present experiment aimed at assessing how
      interindividual differences in alexithymia--a personality trait associated with
      deficits in emotional reactivity and regulation--influence the neural network
      associated with the perception of fear. Using fMRI, we scanned 34 healthy
      subjects while they were passively observing fearful body expressions. Applying a
      dimensional approach, we performed correlation analyses between fear-related
      brain areas and alexithymia scores among all participants. Using a categorical
      approach, we conducted a between-group comparison (13 high vs. 12 low-alexithymia
      subjects). Our results were threefold. First, the right AMG activity in response
      to fearful stimuli was negatively correlated with the level of difficulty to
      identify emotions. Second, PM activity was linked to reduced subjective emotional
      reactivity. Third, the between-group comparison revealed greater activity in
      anterior cingulate cortex (ACC) for high than low-alexithymia scorers. Moreover,
      the relationship between ACC and PM was in opposite direction in individuals with
      high (negative link) and low (positive link) alexithymia. Therefore, compared to
      our previous findings, we hereby further reveal how ACC interacts with PM to
      sustain self-regulation of one's own emotional state in response to threatening
      social signals. Moreover, this neural mechanism could account for the description
      of the "cold-blooded" personality of individuals with alexithymia.

PMID- 20127874
TI  - Formulation and characterization of radio-opaque conjugated in situ gelling
      materials.
AB  - X-ray visibility is an integral design component of in situ gelling embolization
      systems for neurovascular treatment. The goals of this project included the
      synthesis and characterization of a unique intrinsically radio-opaque in situ
      gelling material for neurovascular embolization. The gels formed using Michael
      Type Addition between pentaerythritol tetrakis 3-mercaptopropionate (QT) thiols
      and poly(propylene glycol) diacrylate (PPODA) with the addition of the new
      material Iodobenzoyl poly(ethylene glycol) acrylate (IPEGA), a radio-opaque
      agent, synthesized successfully as confirmed with (1)H NMR. The PPODA and IPEGA
      were mixed using a syringe coupler with QT and buffer at pH 11 for 90 seconds.
      Gel mixes were weighed to provide equal molar thiols and acrylate groups,
      changing the present acrylate-bearing compounds wt % ratios from 100 PPODA: 0
      IPEGA, 90:10, 80:20, 70:30, 60:40, 50:50, and 0:100. Formulations with 10% and
      above of IPEGA were X-ray visible. Rheology showed that increasing the amount of
      IPEGA decreased the storage. Kinetic FT-IR studies indicate that the amphiphilic
      nature of the PEG backbone increased the reaction rate of the phase segregated
      reactants. Second order reaction constant modeling showed a change in initial
      reaction rate from 0.0029 to 0.0187 (M sec)(-1) from the 10% to 50% IPEGA
      formulations respectively.

PMID- 20127875
TI  - Beneficial effects of quercetin on sperm parameters in streptozotocin-induced
      diabetic male rats.
AB  - Quercetin (QR) is a strong antioxidant and has been shown to reduce oxidative
      stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in
      animal models. Antioxidants have significant effects on spermatogenesis, sperm
      biology and oxidative stress, and changes in antioxidant capacity are considered
      to be involved in the pathogenesis of chronic diabetes mellitus. The present
      study aims to examine the influence of QR on spermatogenesis in STZ-induced
      diabetes in male Wistar rats. Animals (n = 50) were allocated into five groups:
      Group 1: Control rats given 0.5 ml of 20% glycerol in 0.9% normal saline. Group
      2: Control rats given buffer (pH4.0).Group 3: diabetic controls. Group 4: rats
      given QR 15 mg/kg/day (i.p.). Group 5: STZ + QR rats. Animals were kept in
      standard conditions. At the end of the experiment (28th day), blood samples were
      taken for determination of testosterone, total antioxidant capacity, and levels
      of malondialdehyde and oxidized low-density lipoprotein. All rats were
      euthanized, testes were dissected out and spermatozoa were collected from the
      epididymis for analysis. Sperm numbers, percentages of sperm viability and
      motility, and total serum testosterone increased significantly in QR-treated
      diabetic rats (P < 0.05) compared with control groups. In histopathology,
      degeneration and inflammation in testes cells associated with diabetes were
      improved and testes weights in the QR-treated diabetic group decreased
      significantly in comparison with controls (P < 0.05). We conclude that QR has
      significant beneficial effects on the sperm viability, motility, and serum total
      testosterone and could be effective for maintaining healthy sperm parameters and
      male reproductive function in diabetic rats.

PMID- 20127876
TI  - Re: Sonographic measurement of cross-sectional area of the median nerve in the
      diagnosis of carpal tunnel syndrome: correlation with nerve conduction studies.

PMID- 20127877
TI  - Role of sonography in the emergency room to diagnose sternal fractures.
AB  - BACKGROUND: The diagnosis of a sternal fracture is often difficult when the
      fracture site shows only minimal displacement on conventional radiography.
      Recently, sonography (US) has been used widely in the emergency room (ER). We
      investigated the diagnostic performance of US in the ER for the diagnosis of
      sternal fractures. METHOD: Thirty-six consecutive patients examined for pain and
      tenderness in the sternum after blunt chest trauma were enrolled in the study.
      Antero-posterior and lateral radiographs and sonograms of the sternum were
      obtained within 24 hours after admission. The 2 imaging modalities were
      interpreted in a blinded manner and their diagnostic sensitivity and specificity
      were calculated. The final diagnosis was based on results from the clinical
      examination, radiographs, and sonograms. RESULT: Twenty-four of the 36 patients
      were diagnosed with sternal fractures. The sensitivity and specificity of the
      plain radiographs were 70.8% (95% CI = 56.0-85.6%) and 75.0% (95% CI = 60.9
      89.1%), respectively. In contrast, sonography had a 100% sensitivity and
      specificity (95% CI = 90.3-100%). CONCLUSION: US has a higher sensitivity and
      specificity in diagnosing sternal fractures than conventional radiographs. US
      should be considered in patients with symptoms suggesting sternal fractures whose
      radiographs remain indeterminate.

PMID- 20127878
TI  - Concentration-dependent effect of (-) epicatechin in hypertensive patients.
AB  - Non-vitamin polyphenolic compounds are ubiquitous in food plants and therefore
      potentially present in human plasma in a diet-dependent concentration. The aim of
      this study was to evaluate the concentration-dependent effect of (-) epicatechin,
      a polyphenol present in green tea with antioxidant activity, on various
      biomarkers of oxidative stress. The current study examined the in vitro
      concentration-dependent (10(-4) M to 10(-7) M) effects of (-) epicatechin on
      biomarkers of oxidative stress viz. malondialdehyde (MDA), reduced glutathione
      (GSH), membrane sulfhydryl (-SH) group and protein carbonyl content in
      hypertensive patients and normal ones. This effect seems to be due to ability of
      (-) epicatechin to reduce MDA and protein carbonyl content while increase in GSH
      and membrane -SH group in hypertensive patients. It can be concluded that (-)
      epicatechin exerts an antioxidant action inside the cell, responsible for the
      observed modulation of cellular response to oxidative challenges.

PMID- 20127880
TI  - Relaxed energetic maps of kappa-carrabiose: a DFT study.
AB  - The B3LYP density function was used with the 6-31G(d) basis set to perform
      relaxed energetic contour maps of the charged form of kappa-carrabiose in the gas
      phase and for the neutral form first in the gas phase and then by simulating the
      presence of water as solvent using the Onsager model. Only one starting
      conformation has been considered to perform all the calculations. Rigid energetic
      maps have been then constructed either by addition of diffuse or polarization
      functions to the basis set obtaining in that way 6-31+G(d)//6-31G(d), 6
      31+G(d,p)//6-31G(d), and 6-311++G(d,p)//6-31G(d) energetic maps that have been
      carefully examined. The obtained structures corresponding to the lower energy
      conformers have been then fully optimized using different basis sets with the
      B3LYP method, a reversion in term of energy has been observed for the two first
      minima in the case of the charged disaccharide in the gas phase, this was
      attributed to the large grid of 30 degrees that could lead to the exclusion of an
      intermediate value corresponding to the real minimum of energy. We thus suggest
      that after establishing potential energy maps it is essential to proceed to full
      optimizations of the lower energy conformers. Calculations using the more
      accurate correlated method MP2 with the 6-31G(d) basis set have also been
      performed for conformers of the two disaccharides in the gas phase.

PMID- 20127879
TI  - Ursolic acid and luteolin-7-glucoside improve lipid profiles and increase liver
      glycogen content through glycogen synthase kinase-3.
AB  - In the present study, two phytochemicals - ursolic acid (UA) and luteolin-7
      glucoside (L7G) - were assessed in vivo in healthy rats regarding effects on
      plasma glucose and lipid profile (total cholesterol, HDL and LDL), as well as
      liver glycogen content, in view of their importance in the aetiology of diabetes
      and associated complications. Both UA and L7G significantly decreased plasma
      glucose concentration. UA also significantly increased liver glycogen levels
      accompanied by phosphorylation of glycogen synthase kinase-3 (GSK3). The increase
      in glycogen deposition induced by UA (mediated by GSK3) could have contributed to
      the lower plasma glucose levels observed. Both compounds significantly lowered
      total plasma cholesterol and low-density lipoprotein levels, and, in addition, UA
      increased plasma high-density lipoprotein levels. Our results show that UA
      particularly may be useful in preventable strategies for people at risk of
      developing diabetes and associated cardiovascular complications by improving
      plasma glucose levels and lipid profile, as well as by promoting liver glycogen
      deposition.

PMID- 20127881
TI  - Combination of the Metropolis Monte Carlo and Lattice Statics method for geometry
      optimization of H-(Al)-ZSM-5.
AB  - In this article, the combination of the Metropolis Monte Carlo and Lattice
      Statics (MMC-LS) method is applied to perform the geometry optimization of
      crystalline aluminosilicate zeolite system in the presence of cationic species
      (H(+)), i.e., H-(Al)-ZSM-5. It has been proved that the MMC-LS method is very
      useful to allow H(+) ions in (Al)-ZSM-5 extra-framework to approach the global
      minimum energy sites. The crucial advantage of the combination MMC-LS method is
      that, in stead of simulating over thousands random configurations via the only LS
      method, the only one configuration is needed for the MMC-LS simulation to achieve
      the lowest energy configuration. Therefore, the calculation time can be
      substantially reduced via the performance of the MMC-LS method with respect to
      the only LS method. The calculated results obtained from the MMC-LS and the only
      LS methods have been comparatively represented in terms of the thermodynamic and
      structural properties.

PMID- 20127882
TI  - Effects of Machilus thunbergii Sieb et Zucc on UV-induced photoaging in hairless
      mice.
AB  - Chronic ultraviolet (UV) exposure induces photoaging and oxidative stress in the
      skin. We investigated whether Machilus thunbergii Sieb et Zucc (M. thunbergii)
      could reduce UV-induced photoaging and oxidative stress in hairless mice. The
      dorsal skin of hairless mice was treated topically with M. thunbergii for 2 h
      prior to UV irradiation. Malondialdehyde (MDA) and superoxide dismutase (SOD)
      levels were then measured in skin and/or serum samples. Histological changes in
      the skin were assessed by hematoxylin-eosin (HE) staining. In addition, proteomes
      from the skin of hairless mice in each group were analyzed. The thickness of the
      dorsal skin and epidermis was significantly decreased by M. thunbergii treatment.
      We also found that MDA levels decreased after M. thunbergii treatment and the SOD
      levels were increased by M. thunbergii compared with those in the UV-only treated
      group. Proteomic analysis revealed 17 proteins associated with photoaging. These
      data indicate that M. thunbergii might have antiphotoaging effects.

PMID- 20127883
TI  - Neotropics and natural ingredients for pharmaceuticals: why isn't South American
      biodiversity on the crest of the wave?
AB  - Despite the advent of biotechnology and modern methods of combinatorial chemistry
      and rational drug design, nature still plays a surprisingly important role as a
      source of new pharmaceutical compounds. These are marketed either as herbal drugs
      or as single active ingredients. South American tropical ecosystems (or the
      Neotropics) encompass one-third of the botanical biodiversity of the planet. For
      centuries, indigenous peoples have been using plants for healing purposes, and
      scientists are making considerable efforts in order to validate these uses from a
      pharmacological/phytochemical point of view. However, and despite the unique
      plant diversity in the region, very few natural pharmaceutical ingredients from
      this part of the world have reached the markets in industrialized countries. The
      present review addresses the importance of single active ingredients and herbal
      drugs from South American flora as natural ingredients for pharmaceuticals; it
      highlights the most relevant cases in terms of species of interest; and discusses
      the key entry barriers for these products in industrialized countries. It
      explores the reasons why, in spite of the region's competitive advantages, South
      American biodiversity has been a poor source of natural ingredients for the
      pharmaceutical industry.

PMID- 20127884
TI  - SNPs in CAST are associated with Parkinson disease: a confirmation study.
AB  - Using data from the National Institutes of Neurological disease and Stroke's
      (NINDS) study of Parkinson disease (PD), we recently reported that single
      nucleotide polymorphisms (SNPs) in a region containing the Calpastatin (CAST)
      gene were associated with PD. Here we follow up this finding with an analysis of
      the Center for Inherited Disease Research's (CIDR) genome-wide association study
      in familial PD. After adjusting for population stratification and multiple
      testing, we find a significant association (P = 0.0167) between PD and SNP
      rs1559085 in CAST. These findings confirm CAST/PD associations in a second,
      independent, dataset and suggest that CAST be prioritized for further
      investigation.

PMID- 20127885
TI  - Analysis of whole genome biomarker expression in blood and brain.
AB  - The consistency of peripheral gene expression data and the overlap with brain
      expression has not been evaluated in biomarker discovery, nor has it been
      reported in multiple tissues from the same subjects on a genome wide transcript
      level. The effects of processing whole blood, transformation, and passaged cell
      lines on gene expression profiling was studied in healthy subjects using
      Affymetrix arrays. Ficoll extracted peripheral blood mononuclear cells (PBMCs),
      Epstein-Barr virus (EBV) transformed lymphocytes, passaged lymphoblastic cell
      lines (LCLs), and whole blood from Tempus tubes were compared. There were 6,813
      transcripts differentially expressed between different methods of blood
      preparation. Principal component analysis resolved two partitions involving pre-
      and post-transformation EBV effects. Combining results from Affymetrix arrays,
      postmortem subjects' brain and PBMC profiles showed co-expression levels of
      summarized transcripts for 4,103 of 17,859 (22.9%) RefSeq transcripts. In a
      control experiment, rat hemi-brain and blood showed similar expression levels for
      19% of RefSeq transcripts. After filtering transcripts that were not
      significantly different in abundance between human cerebellum and PBMCs from the
      Affymetrix exon array the correlation in mean transcript abundance was high as
      expected (r = 0.98). Differences in the alternative splicing index in brain and
      blood were found for about 90% of all transcripts examined. This study
      demonstrates over 4,100 brain transcripts co-expressed in blood samples can be
      further examined by in vitro and in vivo experimental studies of blood and cell
      lines from patients with psychiatric disorders.

PMID- 20127886
TI  - Sexually dimorphic interaction between the DRD1 and COMT genes in schizophrenia.
AB  - Dopaminergic dysfunction in the prefrontal cortex (PFC) is involved in the
      pathophysiology of schizophrenia. In the PFC, dopamine signalling largely depends
      on the D1 receptors, which are coded by the DRD1 gene, and on the regulation of
      dopamine levels by the enzyme catechol-O-methyltransferase (COMT). Here, we
      investigate the role of DRD1 and its interaction with the COMT gene in
      schizophrenic patients. In two gender-limited independent patient and control
      samples, we genotype five Tag single nucleotide polymorphisms (tagSNPs) of DRD1.
      The DRD1 SNP and haplotype associations, as well as interaction effects with the
      Val158Met COMT SNP were analyzed. In the male sample, we found the rs11746641 and
      rs11749676 DRD1 SNPs were associated with schizophrenia. Haplotype analyses
      identified the T-A-T-C-T variant related to a protective effect (P = 0.008) and
      the G-G-T-C-C variant that showed a tendency to be a risk factor for the disorder
      (P = 0.012). A logistic regression analysis revealed a significant pattern of
      interaction between DRD1 and COMT for both the rs11746641 (P = 0.002) and
      rs11749676 (P = 4.5 x 10(-5)) SNPs. DRD1-associated haplotypes were exclusively
      related to schizophrenia in the Val homozygous subgroup of patients (T-A-T-C-T: P
      = 0.003; G-G-T-C-C: P = 0.006). In females, none of the DRD1 SNPs were linked to
      the disorder. Our genetic data suggest that DRD1 and COMT are epistatically
      associated with protection against and the risk of developing schizophrenia in a
      gender-dependent fashion, and support the role of dopamine dysfunction at the PFC
      in the pathophysiology of this disorder.

PMID- 20127887
TI  - Development of role-differentiated bimanual manipulation during the infant's
      first year.
AB  - Role-differentiated bimanual manipulation (RDBM) is a complementary movement of
      both hands that requires differentiation between actions of the hands. Previous
      research showed that RDBM can be observed in infants as early as 7 months.
      However, RDBM could be considered a skill only when its frequency, duration, and
      use is appropriate for the type of manual task, and there is some evidence of
      intentionality in use. Twenty-four normally developing infants were studied
      longitudinally at 7, 9, 11, and 13 months to assess the frequency and duration of
      five clearly different types of RDBM with three "single-part" and three "two
      part" toys as they emerge during development. Also, the sequences of actions that
      lead to RDBM were examined for evidence of "intentionality." The results show
      that although the each type of RDBM appears early in infancy, RDBM only begins to
      exhibit the characters of a skill by 13 months. Moreover, the type of toy
      influences not only the likelihood of eliciting role differentiation, but also
      the type of RDBM behavior and the organization of the sequence of actions that
      lead to RDBM. Some useful criteria for defining an infant sensorimotor skill are
      provided in discussion.

PMID- 20127888
TI  - Evaluation of semiochemical toxicity to Aedes aegypti, Ae. albopictus and
      Anopheles quadrimaculatus (Diptera: Culicidae).
AB  - BACKGROUND: Mosquitoes are the most important vectors of human pathogens. Wide
      scale use of pesticides has led to the development of resistance to most common
      insecticide groups. The need to develop novel products that have a low impact on
      human health and the environment is well established. The toxicity of selected
      semiochemicals with molecular structures indicative of insecticidal activity was
      determined against adult Aedes aegypti (L.) and Anopheles quadrimaculatus (Say).
      The two most active insecticides against Ae. aegypti were also evaluated against
      Ae. albopictus (Skuse). RESULTS: Fifteen semiochemicals classified as terpenoid
      alcohols, ketones or carboxylic esters showed toxicity to both mosquito species.
      Geranyl acetone (LC(50) = 38.51 microg cm(-2)) followed by citronellol (LC(50) =
      48.55 microg cm(-2)) were the most toxic compounds to Ae. aegypti, while geraniol
      and lavonax, with LC(50) values of 31.88 and 43.40 microg cm(-2), showed the
      highest toxicity to An. quadrimaculatus. Both geranyl acetone and citronellol
      were highly toxic to Ae. albopioctus. No semiochemical showed fumigation activity
      against either species. All semiochemicals persisted for less than 24 h when
      tested on filter paper. CONCLUSION: Quantification of LC(50) values of several
      semiochemicals against Ae. Aegypti, An. quadrimaculatus and Ae. albopioctus
      showed that semiochemicals not only modify insect behaviors but also hold
      potential as potent insecticides for mosquito control programs.

PMID- 20127890
TI  - Theoretical evaluation of magnetoreception of power-frequency fields.
AB  - Several effects of power-frequency (50/60 Hz) magnetic fields (PF-MF) of weak
      intensity have been hypothesized in animals and humans. No valid mechanism,
      however, has been proposed for an interaction between PF-MF and biological
      tissues and living beings at intensities relevant to animal and human exposure.
      Here we proposed to consider PF-MF as disrupters of the natural magnetic signal.
      Under exposure to these fields, an oscillating field exists that results from the
      vectorial summation of both the PF-MF and the geomagnetic field. At a PF-MF
      intensity (rms) of 0.5 microT, the peak-to-peak amplitude of the axis and/or
      intensity variations of this resulting field exceeds the related discrimination
      threshold of magnetoreception (MR) in migrating animals. From our evaluation of
      the 50/60 Hz responsiveness of the putative mechanisms of MR, single domain
      particles (Kirschvink's model) appear unable to transduce that oscillating
      signal. On the contrary, radical pair reactions are able to, as well as
      interacting multidomain iron-mineral platelets and clusters of superparamagnetic
      particles (Fleissner/Solov'yov's model). It is, however, not yet known whether
      the reception of 50/60 Hz oscillations of the natural magnetic signal might be of
      consequence or not.

PMID- 20127889
TI  - How the epigenome contributes to the development of psychiatric disorders.
AB  - Epigenetics commonly refers to the developmental process by which cellular traits
      are established and inherited without a change in DNA sequence. These mechanisms
      of cellular memory also orchestrate gene expression in the adult brain and recent
      evidence suggests that the "epigenome" represents a critical interface between
      environmental signals, activation, repression and maintenance of genomic
      responses, and persistent behavior. We here review the current state of knowledge
      regarding the contribution of the epigenome toward the development of psychiatric
      disorders.

PMID- 20127891
TI  - Prognostic factors in stage IB-IIB cervical adenocarcinoma patients treated with
      radical hysterectomy and pelvic lymphadenectomy.
AB  - OBJECTIVES: The purpose of the present study was to identify prognostic factors
      and patterns of recurrence in patients with stage IB-IIB cervical adenocarcinoma
      who had undergone radical surgery and to compare these patterns with those
      observed in squamous cell carcinoma (SCC) patients. METHODS: We retrospectively
      reviewed 303 patients (97 with adenocarcinoma and 206 with SCC) with stage IB-IIB
      cervical cancer who had undergone radical hysterectomy and pelvic
      lymphadenectomy. RESULTS: In the case of the adenocarcinoma patients, lymph node
      metastasis and parametrial invasion were independent indicators of disease-free
      survival, whereas lymph node metastasis was the only independent prognostic
      factor for the overall survival of the patients. The sites of recurrence did not
      significantly differ between the adenocarcinoma and SCC patients. In parametrium
      positive patients, adenocarcinoma was found to be an independent prognostic
      factor for disease-free survival. In patients with positive pelvic lymph node,
      adenocarcinoma was found to be an independent prognostic factor for both disease
      free and overall survival. CONCLUSIONS: Adenocarcinoma was found to be an
      independent prognostic factor for survival in patients with positive pelvic node
      or parametrial extension. Furthermore, the patterns of recurrence did not differ
      significantly between the adenocarcinoma and SCC patients.

PMID- 20127892
TI  - Clinical significance of the discrepancy between preoperative and postoperative
      diagnoses in gastric cancer patients.
AB  - BACKGROUND: Discrepancies between pre- and postoperative diagnoses can lead to
      dilemma for operative management adequacy. PATIENTS AND METHODS: A total of 2,910
      patients with gastric adenocarcinoma underwent curative surgery at the Samsung
      Medical Center between 2001 and 2003. Patients were divided into four groups:
      early gastric cancer (EGC)-EGC group that consisted of subjects who were
      diagnosed as having EGC pre- and postoperatively, advanced gastric cancer (AGC)
      EGC group, EGC-AGC group, and AGC-AGC group. Clinicopathologic features and
      survival rates of groups were analyzed retrospectively. RESULTS: Of the 2,910
      patients, 1,491 (51.2%) patients were included in the EGC-EGC group, 132 (4.5%)
      in the AGC-EGC group, 120 (4.1%) in the EGC-AGC group, and 1,167 (40.1%) in the
      AGC-AGC group. The EGC-AGC group showed higher proportions of the followings than
      the EGC-EGC group: upper-third and middle-third tumor localizations, a tumor size
      from 2 to 5 cm, undifferentiated adenocarcinoma, Lauren's diffuse type,
      endolymphatic invasion, vascular invasion, and perineural invasion. Five-year
      survival rates were dependent on the final pathologic stages, not on the
      preoperative stages. Multivariate analysis revealed that age and American Joint
      Committee of Cancer stage were independent prognostic factors of patient
      survival. CONCLUSION: A decision regarding minimally invasive treatment for EGC
      must be made having considered tumor location, size, and cellular
      differentiation, because of the possibility of an incorrect preoperative
      diagnosis.

PMID- 20127893
TI  - Experienced clinicians improve detection of third and fourth heart sounds by
      viewing acoustic cardiography.
AB  - BACKGROUND: Clinical assessment of diastolic heart sounds is challenging.
      HYPOTHESIS: We sought to examine whether visual inspection of acoustic
      cardiographic tracings augments the accuracy of medical students' and physicians'
      detection of third and fourth heart sounds (S(3), S(4)) compared to auscultation
      alone. METHODS: A total of 90 adults referred for left heart catheterization
      underwent digital precordial heart sound recordings by computerized acoustic
      cardiography. Two blinded, experienced readers using a consensus method
      determined the presence of the S(3)/S(4) on each file. There were 35 subjects
      from the following 5 groups participating in this study from 1 teaching
      institution: first-year medical students (n = 5), fourth-year medical students (n
      = 5), interns (n = 5), medicine residents (n = 5), cardiology fellows (n = 5),
      and attendings (n = 10). Using a computer module, each subject listened to the
      heart sounds alone and documented whether an S(3)/S(4) was present. Next,
      subjects listened to each recording in random order while viewing
      phonocardiographic tracings, and recorded S(3)/S(4) presence. RESULTS: An S(3)
      was present in 21 patients (23%) and an S(4) in 31 patients (34%) by consensus
      overread in 90 recordings. Baseline accuracy for auscultation of S(3)/S(4) did
      not change with level of experience. While viewing the acoustic cardiogram, first
      year medical students had minimal improvement in S(3) (2%) and S(4) (11%)
      accuracy. More experienced subjects improved S(3) accuracy by 8% to 18% and S(4)
      by 15% to 32% (P < .05). Accuracy was superior for S(3) compared to S(4) in all
      ausculatory groups. CONCLUSIONS: While listening to heart sound recordings,
      viewing acoustic cardiography increased subjects' accuracy in detecting diastolic
      heart sounds, particularly among more experienced subjects. There was greater
      improvement for S(4) compared to S(3) detection.

PMID- 20127894
TI  - Right ventricular function suffers from reperfusion delay: tissue Doppler study.
AB  - In this study, impact of reperfusion delay on adverse cardiac events and right
      ventricular (RV) function in patients with acute right ventricular myocardial
      infarction (RVMI) was assessed. In 70 patients with RVMI, RV function was
      assessed by M-mode tricuspid annular plane systolic excursion (TAPSE) and by
      pulsed wave tissue Doppler echocardiography (TDE). Right ventricular early
      (E'(T)) and late diastolic (A'(T)), peak systolic tricuspid annular velocity,
      (S'(T)) and right ventricular myocardial performance index (RVMPI) were measured.
      Patients were divided into 2 groups according to the time between the onset of
      symptoms and percutaneous transluminal coronary angioplasty (PTCA)-group 1 (n =
      25), < or =3 hours and group 2 (n = 45), > 3 hours. During 30-day follow-up, we
      assessed adverse cardiac events like the following: death, cardiogenic shock,
      need for intra-aortic counterpulsation, temporary transvenous pacing support
      (PCM), presence of ventricular septal defect (VSD), cardiac tamponade, or free
      wall rupture. RESULTS: Group 1 had significantly higher values of E'(T), S'(T),
      and TAPSE than group 2. RVMPI was significantly elevated in group 2. A total of
      13 (18.2%) patients had a cardiac event, 5 patients (7.1%) died. We observed an
      increase of cardiac events in patients with reperfusion delayed more than 3 hours
      (P = .056). CONCLUSION: TAPSE-derived and TDE-derived right ventricular systolic
      and early diastolic velocities were less affected in patients with shorter time
      from pain onset to opening of the occluded right coronary artery (RCA). Presented
      initial data show that the tissue Doppler technique may be useful for
      identification of patients with RV infarction with higher rate of adverse cardiac
      events including death.

PMID- 20127895
TI  - A case of Brugada syndrome presenting with incessant polymorphic ventricular
      tachycardia.
AB  - Brugada syndrome, an inherited arrhythmogenic cardiac disease, manifests with ST
      segment changes in the right precordial leads, right bundle block pattern, and
      susceptibility to ventricular tachyarrhythmias and sudden death. The only
      established therapy for this disease is prevention of sudden death by
      implantation of a defibrillator. Herein we describe a case of a patient who
      presented with incessant ventricular tachycardia (VT) and syncope and who had a
      type 1 Brugada pattern on ECG. The patient was successfully treated with
      quinidine, after which the classically described type 2 and 3 patterns emerged.

PMID- 20127896
TI  - Statin therapy in patients with diastolic heart failure.
AB  - BACKGROUND: There is controversy regarding the potential effects of statin
      therapy on mortality in patients with heart failure. The present study analyzed
      the possible effects of statin therapy on morbidity and mortality in patients
      with diastolic heart failure over long-term follow-up. HYPOTHESIS: To evaluate
      potential effect of statin therapy on hospitalization rate and mortality in
      patients with diastolic heart failure. METHODS: Patients with preserved left
      ventricular ejection fraction (> or =50%), hospitalized for clinical symptoms of
      heart failure were evaluated. Patients on statin therapy started at or prior to
      their first heart failure admission represented group 1 and patients without
      statin therapy represented group 2. The effects of statins on hospitalization
      rates and mortality were assessed during a 5 year follow-up. RESULTS: A total of
      270 patients (group 1 n = 81; group 2 n = 189) were followed over 5 years.
      Patients on statins demonstrated improved survival compared to patients without
      statin therapy (hazard ratio [HR] = 0.65, 95% confidence interval [CI]: 0.45
      0.95, P = .029). The survival benefit was maintained after adjusting for
      differences in baseline characteristics, comorbidities, and other medications.
      There was no significant difference in the mean cardiovascular hospitalization
      rate (3.0 +/- 3.2 vs 3.8 +/- 4.7, P = .23) and in overall hospitalization rate
      (7.1 +/- 6.3 vs 7.8 +/- 7.7, P = .52) between groups 1 and 2, respectively.
      CONCLUSION: Statin therapy appears to be associated with improved survival in
      patients with diastolic heart failure.

PMID- 20127897
TI  - Circulating cell-free DNA levels increase variably following chorionic villus
      sampling.
AB  - OBJECTIVE: Cell-free fetal DNA (cffDNA) in maternal plasma results from
      degradation of fetal and/or placental cells. Our objective was to determine if
      chorionic villus sampling (CVS) causes increased release of fetal and/or maternal
      DNA. METHODS: Fifty-two pregnant women were recruited prior to CVS, performed for
      clinical indications, at 10 5/7 to 13 2/7 weeks. Maternal blood was collected
      before and within 15 min after CVS. cffDNA was extracted from plasma. Real-time
      polymerase chain reaction (PCR) amplification of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and the Y chromosome sequence DYS1 were used as measures of
      total and fetal DNA, respectively. All samples were analyzed in triplicate
      without knowledge of fetal gender. RESULTS: Sensitivity of DYS1 detection in male
      fetuses was 100% (n = 30); specificity in female fetuses was 100% (n = 22). While
      a majority of women had > 50% post-procedure increases in both fetal and total
      DNA, some showed post-procedure decreases. However, overall median proportional
      increases were not statistically significant. Gestational age (GA), placental
      location, and individual CVS operator did not correlate with changes in DNA
      levels. CONCLUSIONS: While there were no statistically significant overall
      changes in DNA levels after CVS, as-yet undiscovered variables may influence the
      extent of post-procedure release of cell-free DNA in the circulation of pregnant
      women.

PMID- 20127898
TI  - Surgical resection for pulmonary metastasis from hepatocellular carcinoma:
      analysis of prognosis in relation to primary control.
AB  - BACKGROUND: Advances in local treatments for hepatocellular carcinoma (HCC) have
      seen better prognosis. There were few studies on surgery for pulmonary metastasis
      from HCC controlled by local treatment. This study was conducted to analyze
      prognostic factors after surgery for pulmonary metastasis from HCC. METHODS: We
      reviewed 32 patients who underwent surgery for pulmonary metastasis from HCC and
      analyzed prognostic factors. RESULTS: HCC was controlled by surgery in 16
      patients and by local treatment in 16 patients at the time of pulmonary
      resection. The median survival time after pulmonary resection was significantly
      better for HCC controlled by surgery, disease-free time >or=12 months, TMN stage
      I-II, and T factor 1-2 of primary HCC. The median survival time was better for
      lesion <or=2 and Child-Pugh score A, but they were not significant (P = 0.053,
      0.069). In multivariate analysis, HCC controlled by surgical treatment (P =
      0.008), and lesion <or=2 (P = 0.030) were independent prognostic factors.
      CONCLUSION: Our Results indicated that surgical resection for pulmonary
      metastasis from HCC might be beneficial for patients whose HCC was controlled by
      surgery and the number of lesions was lower than 3.

PMID- 20127899
TI  - Increased concentrations of antiangiogenic factors in mirror syndrome
      complicating twin-to-twin transfusion syndrome.

PMID- 20127900
TI  - Prevention of contrast-induced nephropathy: a single center randomized study.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is the third cause of acute
      deterioration of renal function in hospitalized patients. HYPOTHESIS: The purpose
      of the study was to compare the efficacy of saline infusion, saline infusion plus
      N-acetylcysteine (NAC), and sodium bicarbonate (SB) infusion to prevent CIN in
      patients undergoing coronary angiography and/or percutaneous coronary
      intervention. METHODS: We prospectively studied 156 patients with a baseline
      creatinine level > or = 1.2 mg/dL. The primary endpoint was the development of
      CIN, defined as an increase in serum creatinine concentration > or = 25% over the
      baseline value within 5 days from contrast exposure. RESULTS: Contrast-induced
      nephropathy developed in 23 patients (14.7%). Incidence of the primary endpoint
      was similar in the 3 groups of treatment, occurring in 7 patients (14%) in the
      saline infusion group, in 9 (17%) in the saline infusion plus NAC group, and in 7
      (14%) in the SB infusion group. CONCLUSIONS: Our findings suggest that neither
      the addition of NAC nor the administration of SB add further benefit in CIN
      prevention, compared to standard hydration with isotonic saline infusion.

PMID- 20127901
TI  - Atrial electroanatomical remodeling as a determinant of different outcomes
      between two current ablation strategies: circumferential pulmonary vein isolation
      vs pulmonary vein isolation.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship between
      the efficacy of the 2 different ablation techniques of atrial fibrillation (AF)
      and left atrial (LA) size. METHODS AND RESULTS: A total of 81 patients with
      paroxysmal AF (n = 58) or persistent AF (n = 23) refractory to antiarrhythmic
      drugs underwent circumferential pulmonary vein isolation (PVI; n = 45) or PVI (n
      = 36) without respect to echocardiographic results for LA volume index (LAVI). Of
      the 81 patients, 41 had less dilated LA (group 1; LAVI < 27 cc/m(2)) and 40 had
      dilated LA (group 2; LAVI > or = 27 cc/m(2)). During the 9-month follow-up, 33
      patients (73.3%) after circumferential PVI and 18 (50%) after PVI (P = .031) were
      free of arrhythmia. The risk of recurrence was associated with persistent AF,
      hypertension, LAVI > 27 ml/m(2), PVI, early recurrence of AF, and lower left
      ventricular (LV) ejection fraction (all P value <.05). In the univariate analysis
      of each group, PVI (hazard ratio [HR]: 2.92, 95% confidence interval [CI]: 0.12
      7.08, P = .018) was associated with late recurrence only in group 2. Cox
      regression analysis also showed that PVI (HR: 5.6, 95% CI: 1.9-16.56, P = .002)
      was a significant independent predictor of recurrence only in group 2.
      CONCLUSIONS: Circumferential PVI is more effective than PVI only in patients with
      a structural change of the atria, that is, a dilated LA. Our study suggests that
      a successful outcome in dilated LA may depend on wide modification of LA
      electroanatomical substrates, but wide ablation in less dilated LA may be
      unnecessary. Different technical strategies according to LA size are required for
      more a effective outcome.

PMID- 20127902
TI  - Paraganglioma resection requiring left atrial reconstruction.
AB  - Paragangliomas, also known as extra-adrenal pheochromocytomas, arise from
      chromaffin cells within the autonomonic ganglia. Catecholamine secreting
      paragangliomas have been described in the mediastinum, but rarely invade the
      heart. This case describes the use of a novel bioabsorbable matrix that was used
      to replace a tumor invading the posterior left atrium.

PMID- 20127903
TI  - Brain abscess in an adult with atrial septal defect.
AB  - Brain abscess is a serious complication of congenital heart disease in children
      and adolescents. This association is rarely observed in adults. This article
      describes the case of a 41-year-old man who presented with altered mental status.
      Brain MRI showed a brain abscess at the left frontal lobe. The patient was
      successfully treated with surgical removal and appropriate antibiotics.
      Echocardiographic examination showed atrial septal defect (ASD) with
      bidirectional shunt. Transcatheter closure of ASD was carried out 6 months after
      neurosurgical treatment. We discuss the association of brain abscess and ASD.

PMID- 20127904
TI  - Influence of clinical trial participation on subsequent antithrombin use.
AB  - BACKGROUND: Results from the Superior Yield of the New Strategy of Enoxaparin,
      Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial showed
      that the low-molecular-weight heparin (LMWH) enoxaparin was non-inferior compared
      with unfractionated heparin (UFH) in patients with non-ST-elevation acute
      coronary syndromes (NSTE-ACS) managed invasively. HYPOTHESIS: We explored the
      influence of SYNERGY trial site participation on subsequent patterns of heparin
      use for NSTE-ACS patients treated in routine practice. METHODS: We examined
      temporal patterns of LMWH use compared with UFH use among 122 764 patients with
      NSTE-ACS enrolled in the Can Rapid Risk Stratification of Unstable Angina
      Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA
      Guidelines (CRUSADE) quality improvement initiative between January 1, 2002 and
      June 30, 2006, to determine whether site participation in SYNERGY influenced the
      type of heparin used before and after publication of the SYNERGY results in July
      2004. RESULTS: A total of 118 out of 388 (30%) U.S. hospitals participating in
      CRUSADE simultaneously participated in SYNERGY. SYNERGY sites in the CRUSADE
      registry were more likely to have a teaching affiliation and have more hospital
      beds than non-SYNERGY centers in the registry. There was no difference in the
      proportion of patients treated with LMWH at SYNERGY and non-SYNERGY sites prior
      to July 2004 compared with after July 2004. However, at SYNERGY sites, there was
      a slight decrease in the proportion of patients treated with both UFH and LMWH
      within 24 hours of presentation. CONCLUSIONS: The results of the SYNERGY trial
      did not appear to influence temporal patterns of LMWH use at sites in the CRUSADE
      registry. Furthermore, site participation in the SYNERGY trial did not alter
      patterns of LMWH use for NSTE-ACS after publication of the trial results in July
      2004.

PMID- 20127905
TI  - Left ventricular ejection fraction assessment by Tl-201 gated SPECT: a comparison
      with echocardiography.
AB  - BACKGROUND: Few studies including only a limited number of patients have compared
      left ventricular ejection fraction (LVEF) assessed by 2-dimensional
      echocardiography (2-DE) and electrocardiography-gated Tl-201 single-photon
      emission computed tomography (SPECT). HYPOTHESIS: LVEF assessment by Tl-201 gated
      spect is comparable with LVEF assessed by 2-DE in two different echocardiographic
      laboratories. MATERIAL AND METHODS: Patients (n = 402) underwent Tl-201 gated
      SPECT in the same laboratory and 2-DE in 2 different laboratories. Patients were
      divided into 2 groups according to the study laboratory: group 1, at the tertiary
      hospital and group 2, at a community laboratory. RESULTS: LVEF evaluations were
      similar (mean LVEF: 50.73% +/- 11.67% by 2-DE vs 50.11% +/- 11.41% by SPECT in
      group 1 and 57.27% +/- 7.44% by 2-DE vs 57.41% +/- 8.37% by SPECT in group 2).
      All LVEF measurements were highly correlated (r = 0.7, P<.001). Baseline
      characteristics differed between the groups, with a higher prevalence of past
      myocardial infarction in the in-hospital vs the community echo group (46.7% vs
      22.2%, P<.01), resulting in a higher LVEF in the latter, both by 2-DE (mean 50.7%
      +/- 11.7% vs 57.3% +/- 7.4%, P<.01) and SPECT (50.1% +/- 11.4% vs 57.4% +/- 8.4%,
      P<.01). CONCLUSIONS: The Tl-201 gated SPECT is a reliable clinical tool for LVEF
      assessment, with good correlation when compared to 2-DE. It may be routinely used
      as an alternative for patients with poor acoustic visualization and should be
      performed systematically in patients undergoing myocardial perfusion imaging with
      Tl-201.

PMID- 20127906
TI  - The hydrological response of heavy clay grassland soils to rainfall in south-west
      England using delta2H.
AB  - Stable isotopes of water have been previously used in catchment studies to
      separate rain-event water from pre-event groundwater. However, there are a lack
      of studies at the smaller scale looking at the separation of event water from pre
      event water. This is particularly relevant for heavy clay soil systems through
      which the movement of water is uncertain but is thought to be rainwater
      dominated. The data presented here were collected at a rural site in the south
      west of England. The historic rainfall at the site was isotopically varied but
      similar to the global meteoric water line, with annual weighted means of -37 per
      thousand for delta(2)H and -5.7 per thousand for delta(18)O and with no seasonal
      variation. Drainage was sampled from the inter-flow (surface runoff + lateral
      through-flow) and drain-flow (55 cm deep mole drains) pathways of two 1 ha
      lysimeters during two rainfall events, which had delta(2)H values of -68 per
      thousand and -92 per thousand, respectively. The delta(2)H values of the
      lysimeter drainage water suggest that there was no contribution of event water
      during the first, small discharge (Q) event; however, the second larger event did
      show isotopic variation in delta(2)H values negatively related to Q indicating
      that rainwater was contributing to Q. A hydrograph separation indicated that only
      49-58% of the inter-flow and 18-25% of the drain-flow consisted of event water.
      This was surprising given that these soil types are considered retentive of soil
      water. More work is needed on heavy clay soils to understand better the nature of
      water movement from these systems.

PMID- 20127907
TI  - Evidence for the production of NO and N2O in two contrasting subsoils following
      the addition of synthetic cattle urine.
AB  - Nitrogenous materials can be transferred out of the topsoil, either vertically to
      a greater depth, or in lateral pathways to surface waters, and they may also
      become transformed, with the potential of generating environmentally active
      agents. We measured the production of NO and N(2)O in two contrasting subsoils
      (70 to 90 cm): one poorly drained and the other freely drained and compared this
      with the topsoil (0 to 20 cm) of the corresponding soils. The soils were
      incubated aerobically in jars with subtreatments of either synthetic cattle urine
      or deionised water and sampled at intervals up to 34 days. (15)N-NO(3)(-) was
      used to determine the processes responsible for NO and N(2)O production. The
      headspace was analysed for the concentrations of N(2)O, NO and CO(2) and (15)N
      enrichment of N(2)O. The soil samples were extracted and analysed for NO(2)(-),
      NO(3)(-) and NH(4)(+), and the (15)N enrichment of the extracts was measured
      after conversion into N(2)O and N(2). The study demonstrated the potential for
      NO, N(2)O and NO(2)(-) to be generated from subsoils in laboratory incubations.
      Differences in these N dynamics occurred due to subsoil drainage class. In the
      freely drained subsoil the rates of NO and NO(2)(-) production were higher than
      those observed for the corresponding topsoil, with mean maximum production rates
      of 3.5 microg NO(2)(-)-N g(-1) dry soil on day 16 and 0.12 microg NO-N g(-1) dry
      soil on day 31. The calculated total losses of N(2)O-N as percentages of the
      applied synthetic urine N were 0.37% (freely drained subsoil), 0.24% (poorly
      drained subsoil), 0.43% (freely drained topsoil) and 2.09% (poorly drained
      topsoil). The calculated total losses of NO-N as percentages of the applied
      synthetic urine N were 1.53% (freely drained subsoil), 0.02% (poorly drained
      subsoil), 0.25% (freely drained topsoil) and 0.08% (poorly drained topsoil).

PMID- 20127908
TI  - Secreted proteome of the murine multipotent hematopoietic progenitor cell line
      DKmix.
AB  - Administration of the multipotent hematopoietic progenitor cell (HPC) line DKmix
      improved cardiac function after myocardial infarction and accelerated dermal
      wound healing due to paracrine mechanisms. The aim of this study was to analyse
      the secreted proteins of DKmix cells in order to identify the responsible
      paracrine factors and assess their relevance to the wide spectrum of therapeutic
      effects. A mass spectrometry (MS)-based approach was used to identify secreted
      proteins of DKmix cells. Serum free culture supernatants of DKmix-conditioned
      medium were collected and the proteins present were separated, digested by
      trypsin and the resulting peptides were then analyzed by matrix-assisted laser
      desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) MS. Overall 95
      different proteins were identified. Among them, secretory proteins galectin-3 and
      gelsolin were identified. These proteins are known to stimulate cell migration
      and influence wound healing and cardiac remodelling. The remaining proteins
      originate from intracellular compartments like cytoplasm (69%), nucleus (12%),
      mitochondria (4%), and cytoplasmic membrane (3%) indicating permeable or leaky
      DKmix cells in the conditioned medium. Additionally, a sandwich immunoassay was
      used to detect and quantify cytokines and chemokines. Interleukin-6 (IL-6),
      interleukin-13 (IL-13), monocyte-chemoattractant protein-1 (MCP-1), monocyte
      chemoattractant protein-3 (MCP-3), monocyte-chemoattractant protein-1alpha (MIP
      1alpha) and monocyte-chemoattractant protein-1beta (MIP-1beta) were detected in
      low concentrations. This study identified a subset of proteins present in the
      DKmix-conditioned medium that act as paracrine modulators of tissue repair.
      Moreover, it suggests that DKmix-derived conditioned medium might have
      therapeutic potency by promoting tissue regeneration.

PMID- 20127909
TI  - Two different sides of 'chemobrain': determinants and nondeterminants of self
      perceived cognitive dysfunction in a prospective, randomized, multicenter study.
AB  - OBJECTIVE: Complaints of cognitive dysfunction are frequent among cancer
      patients. Many studies have identified neuropsychological compromise associated
      with cancer and cancer therapy; however, the neuropsychological compromise was
      not related to self-reported cognitive dysfunction. In this prospective study,
      the authors examined if confounding factors masked an underlying association of
      self-perceived cognitive function with actual cognitive performance. Determinants
      of self-perceived cognitive dysfunction were investigated. METHODS: Self
      perceived cognitive function and cognitive performance were assessed before
      treatment, at the end of treatment, and 1 year after baseline in 101 breast
      cancer patients randomized to standard versus intensified chemotherapy. Linear
      mixed-effects models were applied to test the relationships of performance on
      neuropsychological tests, patient characteristics, and treatment variables to
      self-reported cognitive function. Change of cognitive performance was tested as a
      predictor of change in self-reports. RESULTS: Self-perceived cognitive function
      deteriorated during chemotherapy and had partially recovered 1 year after
      diagnosis. The personality trait negative affectivity, current depression, and
      chemotherapy regimen were consistently related to cognitive self-reports. No
      significant associations with performance in any of the 12 cognitive tests
      emerged. Change of cognitive performance was not reflected in self-reports of
      cognitive function. CONCLUSIONS: Neuropsychological compromise and self-perceived
      cognitive dysfunction are independent phenomena in cancer patients. Generally,
      cancer-associated neuropsychological compromise is not noticed by affected
      patients, but negative affectivity and treatment burden induce pessimistic self
      appraisals of cognitive functioning regardless of the presence of
      neuropsychological compromise. Clinicians should consider this when determining
      adequate therapy for patients who complain of 'chemobrain'.

PMID- 20127910
TI  - Electrogenerated ferrate(VI) for CE-chemiluminescence detection to determine
      benzenediol isomers.
AB  - Based on the quenched chemiluminescence intensity of the luminol reaction
      sensitized by ferrate(VI) in alkaline medium, a novel CE with on-line inhibited
      method for the simultaneous analysis of benzenediol isomers was developed. The
      ferrate(VI) solution was freshly prepared by electrochemical technique before
      electrophoresis. The parameters influencing detection and separation were
      carefully investigated. Baseline separation of benzenediols including catechol,
      resorcinol, and hydroquinone was achieved in less than 8 min with 5.0 mmol/L
      sodium tetraborate and 2.0 mmol/L luminol at an applied voltage of 18 kV. The
      LODs (S/N=3) for catechol, resorcinol and hydroquinone were determined to be 8.5
      x 10(-9), 8.0 x 10(-7) and 6.5 x 10(-9) mol/L, respectively. Finally, the
      proposed method was applied for phenolic compounds in hair dye.

PMID- 20127911
TI  - Rapid screening and identification of the antioxidants in Hippocampus japonicus
      Kaup by HPLC-ESI-TOF/MS and on-line ABTS free radical scavenging assay.
AB  - In this paper, a method based on HPLC coupled with ESI-TOF/MS and on-line to a
      stable free radical scavenging detection system has been developed to rapidly
      screen and identify the major antioxidants in the water extract of Hippocampus
      japonicus Kaup, a kind of marine medicinal organism. The developed on-line stable
      free radical scavenging detection method of water extract from H. japonicus Kaup
      revealed the presence of three radical scavenging compounds, which were
      simultaneously identified as hypoxanthine, phenylalanine and tryptophane by high
      resolution TOF-MS. To the best of our knowledge, it is original to demonstrate
      the rapid and successful use of HPLC-ESI-TOF/MS and on-line 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonate) diammonium salt free radical scavenging assay
      to directly and simultaneously screen and identify the antioxidants in the water
      extracts of H. japonicus Kaup without any purification. The present method
      provides a useful improvement on the reducing of workload and a powerful tool for
      rapid screening and identification of free radical scavenging compounds in
      complex natural products.

PMID- 20127912
TI  - Use of chain transfer agent attached to silica particles in preparation of
      polystyrene-based stationary phases.
AB  - A new stationary phase has been prepared by attaching a new chain transfer agent
      on silica particles followed by reversible addition-fragmentation chain transfer
      polymerization. Porous silica particles were reacted with 3
      chloropropyltrimethoxysilane followed by sodium diethyl dithiocarbarmate. The
      silica particles were then allowed to undergo radical polymerization with
      styrene. The phase had improved ligand morphology to show better separation
      performance than that of the conventional C18 phase.

PMID- 20127913
TI  - Applications of HILIC for targeted and non-targeted LC/MS analyses in drug
      discovery.
AB  - RP-HPLC has largely been the analytical method of choice in the pharmaceutical
      industry for many years because of the poor aqueous solubility and hydrophobicity
      of most small molecule drug candidates. RP-HPLC coupled to MS has provided an
      excellent analytical tool for qualitatively and quantitatively determining levels
      of drug molecules or drug metabolites for studies such as purity assessment and
      pharmacokinetic profiling. Quantitation of endogenous metabolites is an emerging
      field in drug discovery, gaining popularity for evaluating pharmacokinetic
      pharmacodynamic relationships and targeting activity and efficacy. While RP-HPLC
      MS is suitable for a range of applications, many endogenous molecules, especially
      those found in urine, are small polar compounds that do not retain well by RP
      HPLC. This has made hydrophilic interaction LC (HILIC) an attractive alternative
      and useful approach to polar molecule analysis. Additionally, because HILIC is
      routinely used with traditional RP organic solvents such as ACN and methanol, it
      can be easily coupled to MS. This paper will review selected examples from the
      current literature as well as discuss some new applications from the author's own
      laboratory focusing on the applicability of HILIC to quantitative and qualitative
      profiling of endogenous metabolites in drug discovery.

PMID- 20127914
TI  - Determination of aflatoxins B1, B2, G1, G2 and ochratoxin A in animal feed by
      ultra high-performance liquid chromatography-tandem mass spectrometry.
AB  - A rapid and simple method was developed to determine aflatoxins B1, B2, G1, G2
      and ochratoxin A in animal feed and pet foods by UHPLC-MS/MS. Because the
      complexity of the evaluated matrices, the proposed method is based on sonication
      extraction using an ACN/water mixture (80:20 v/v) followed by a clean-up step
      utilising C(18) as sorbent. Performance parameters of the method were evaluated,
      including linearity, trueness, precision and LOQ. Good linearity was found for
      all mycotoxins, with determination coefficients higher than 0.99 in the range
      considered, using matrix-matched calibration for quantification purposes.
      Recoveries ranged from 84 to 113%, with RSD lower than 20%, whereas LOQs were 5
      microg/kg for the assayed mycotoxins. Finally, the method was successfully
      applied to the analysis of 19 real samples, detecting aflatoxin G2 in two samples
      at 13 and 17 microg/kg respectively, whereas the other mycotoxins were detected
      at trace levels (<LOQ) in five samples.

PMID- 20127915
TI  - Off-line comprehensive two-dimensional hydrophilic interaction x reversed phase
      liquid chromatographic analysis of green tea phenolics.
AB  - The separation of green tea phenolic compounds by comprehensive 2-D LC (LCxLC)
      has been studied. An off-line LCxLC system was designed based on hydrophilic
      interaction chromatography in the first dimension and gradient RP-LC using a C18
      column in the second dimension, to separate compounds based on polarity and
      hydrophobicity, respectively. Green tea was found to contain a complex
      composition of low molecular weight phenolic compounds, identified by
      fluorescence, diode-array and negative ESI-MS detection systems. The LCxLC system
      was characterized by a very high practical peak capacity (>2100, in approximately
      22.5 h) due to the low degree of correlation (r(2)<0.2) between the selected
      separation mechanisms. The proposed methodology demonstrated its suitability for
      the analysis of various groups of phenolic compounds including proanthocyanidins,
      phenolic acids, flavonols and flavonol derivatives, all of which cannot be
      separated in a single analysis by conventional 1-D HPLC methods.

PMID- 20127916
TI  - Screening of N-nitrosamines in tap and swimming pool waters using fast gas
      chromatography.
AB  - N-Nitrosamines (NAms) are suspected human carcinogens that have been identified
      as drinking water and wastewater pollutants. In this work, a sensitive
      screening/confirmation method was proposed for the determination of the most
      toxic NAms that can be found in water samples (N-nitrosodimethylamine, N
      nitrosodiethylamine, N-nitrosodibutylamine, N-nitrosomorpholine, N
      nitrosopiperidine, and N-nitrosopyrrolidine). A sample volume of 250 mL was first
      preconcentrated in an automatic SPE unit and then the extract was concentrated to
      a final volume of 10 microL (providing a preconcentration factor of 25,000).
      Aliquots of the extract were subjected to a rapid screening process (1.6 min) by
      using a short capillary polar column (1.5 m length) and GC with nitrogen
      phosphorous detection. In this way, the high number of samples to be tested
      routinely in a water laboratory is simplified due to a reduction in the analysis
      time. Thus, the screening method acts as a filter that indicates whether target
      analytes are present, above or below the cut-off level (3.8 or 10.4 ng/L), giving
      no false negatives at concentrations below the guide values for NAms in drinking
      water established by different countries. Positive samples (tap and swimming pool
      waters) were then confirmed by GC-MS detection.

PMID- 20127917
TI  - Single-step separation of bioactive flavonol glucosides from Osteomeles
      schwerinae by high-speed counter-current chromatography.
AB  - Two bioactive flavonol glucosides, hyperoside and quercitrin, were successfully
      isolated in one step from the phytochemically unknown medicinal plant Osteomeles
      schwerinae by high-speed counter-current chromatography using a two-phase solvent
      system composed of n-hexane-ethyl acetate-methanol-water (0.5:5.5:1.5:4.5 v/v).
      From 160 mg of crude extract, 2.1 mg of hyperoside (98.6% purity, 83.3% recovery)
      and 4.5 mg of quercitrin (99.2% purity, 81.7% recovery) were separated and then
      their chemical structures were identified by (1)H and (13)C NMR analysis. In
      addition, the isolates were subjected to an in vitro bioassay to evaluate their
      inhibitory activity on rat lens aldose reductase. Both quercitrin and hyperoside
      showed excellent inhibitory activities toward rat lens aldose reductase with the
      IC(50) values of 0.16 and 4.33 microM, respectively, as compared with positive
      control, 3,3-tetramethyleneglutaric acid (28.7 microM). So far, chemical
      constituents and biological activities of O. schwerinae have never been reported.
      This is the first report on the chemical constituents and biological activity of
      this plant using semi-preparative high-speed counter-current chromatography
      separation technique.

PMID- 20127918
TI  - Characterization of stationary phases for reversed-phase chromatography.
AB  - Retention characteristics of seven silica-based chromatographic columns
      (Bidentate C18, Silica-hydride, Spherisorb ODS-1, Resolve C18, XTerra C18,
      XBridge Phenyl and Blaze C8 Polydentate) were compared. The columns differ in the
      character of the support, including silica type B, hydrosilated silica, and
      hybrid silica gel with incorporated methyl groups, or ethylene bridges; further
      in the type of chemically bonded stationary phase, including C(18), C(8) and
      phenyl ligands, endcapped and non-endcapped with single point, bidentate and
      polydentate multi-point attachment to the adsorbent surface. Special attention
      was focused on hydrophobic and polar selectivity, silanol activity and anion
      exclusion. The columns were compared and classified on the basis of the results
      of the classical column performance tests, retention of homologous n
      alkylbenzenes over a broad composition range of aqueous-organic mobile phases and
      of naphthalene sulphonic acids in aqueous mobile phases without organic solvents.

PMID- 20127919
TI  - Size exclusion chromatography--a blessing and a curse of science and technology
      of synthetic polymers.
AB  - Size exclusion chromatography, SEC is one of the most popular methods for the
      separation of different kinds of macromolecules. This critical review gives
      concise information about macromolecules and their behavior in solution, basic
      understanding about principles, instrumentation, and application possibilities of
      SEC, and more in detail discusses drawbacks and pitfalls of the method with the
      emphasis on synthetic polymers. Selected practical advices are included to help
      enhance the quality of SEC results.

PMID- 20127920
TI  - Lead-salt quantum-dot ionic liquids.

PMID- 20127921
TI  - Total synthesis of (+/-)-haliclonacyclamine C.

PMID- 20127922
TI  - Selective oxidative cleavage of Cp* from coordinated GaCp*: naked Ga+ in
      [GaNi(GaCp*)4]+ and [(mu2-Ga)nM3(GaCp*)6]n+.

PMID- 20127923
TI  - Unexpected electrophilic rearrangements of amides: a stereoselective entry to
      challenging substituted lactones.

PMID- 20127924
TI  - Metal-organic framework membranes--high potential, bright future?

PMID- 20127925
TI  - Porous organic polymers: distinction from disorder?

PMID- 20127926
TI  - Evidence for the surface-catalyzed Suzuki-Miyaura reaction over palladium
      nanoparticles: an operando XAS study.

PMID- 20127928
TI  - Peering into the black box of fungal polyketide biosynthesis.

PMID- 20127927
TI  - Identification of the tirandamycin biosynthetic gene cluster from Streptomyces
      sp. 307-9.
AB  - The structurally intriguing bicyclic ketal moiety of tirandamycin is common to
      several acyl-tetramic acid antibiotics, and is a key determinant of biological
      activity. We have identified the tirandamycin biosynthetic gene cluster from the
      environmental marine isolate Streptomyces sp. 307-9, thus providing the first
      genetic insight into the biosynthesis of this natural product scaffold. Sequence
      analysis revealed a hybrid polyketide synthase-nonribosomal peptide synthetase
      gene cluster with a colinear domain organization, which is entirely consistent
      with the core structure of the tirandamycins. We also identified genes within the
      cluster that encode candidate tailoring enzymes for elaboration and modification
      of the bicyclic ketal system. Disruption of tamI, which encodes a presumed
      cytochrome P450, led to a mutant strain deficient in production of late stage
      tirandamycins that instead accumulated tirandamycin C, an intermediate devoid of
      any post assembly-line oxidative modifications.

PMID- 20127929
TI  - Low-energy-barrier proton transfer induced by electron attachment to the
      guanine...cytosine base pair.
AB  - The photoelectron spectrum of the anion of the guanine...cytosine base pair
      (GC)(*-) is recorded for the first time. The observed variation in the spectral
      peak-height ratios with the source conditions suggests the presence of two or
      more anionic isomers. Two maxima of the broad bands in the photoelectron spectrum
      were measured at about 1.9 and about 2.6 eV. These values are very well
      reproduced by the vertical detachment energies of the B3LYP/6-31++G(d,p)
      calculated low-energy anionic structures, which are 1) the Watson-Crick base-pair
      anion with proton transferred from N1 of guanine to N3 of cytosine, 2) its
      analogue in which the proton is transferred from N9 of guanine to N7 of guanine,
      and 3) the global minimum geometry, which is formed from the latter anion by
      rotation of guanine about the axis approximately defined by C2 of guanine and C4
      of cytosine. Furthermore, a minor difference in the stabilities of the two lowest
      energy anions explains the experimentally observed source (temperature)
      dependence of the PES spectrum. A rational procedure, based on the chemistry
      involved in the formation of anionic dimers, which enables the low-energy anions
      populated in the photoelectron spectrum to be identified is proposed. In contrast
      to the alternative combinatorial approach, which in the studied case would lead
      to carrying out quantum chemical calculations for 2000-2500 structures, the
      procedure described here reduces the computational problem to only 15 geometries.

PMID- 20127930
TI  - Singlet energy dissipation in the photosystem II light-harvesting complex does
      not involve energy transfer to carotenoids.
AB  - The energy dissipation mechanism in oligomers of the major light-harvesting
      complex II (LHC II) from Arabidopsis thaliana mutants npq1 and npq2, zeaxanthin
      deficient and zeaxanthin-enriched, respectively, has been studied by femtosecond
      transient absorption. The kinetics obtained at different excitation intensities
      are compared and the implications of singlet-singlet annihilation are discussed.
      Under conditions where annihilation is absent, the two types of LHC II oligomers
      show distributive biexponential (bimodal) kinetics with lifetimes of
      approximately 5-20 ps and approximately 200-400 ps having transient spectra
      typical for chlorophyll excited states. The data can be described kinetically by
      a two-state compartment model involving only chlorophyll excited states. Evidence
      is provided that neither carotenoid excited nor carotenoid radical states are
      involved in the quenching mechanism at variance with earlier proposals. We
      propose instead that a chlorophyll-chlorophyll charge-transfer state is formed in
      LHC II oligomers which is an intermediate in the quenching process. The relevance
      to non-photochemical quenching in vivo is discussed.

PMID- 20127931
TI  - Processing of pictorial food stimuli in patients with eating disorders--a
      systematic review.
AB  - OBJECTIVE: The processing of food cues in eating-disordered patients has recently
      been increasingly investigated. Outlined is current evidence from pictorial food
      stimuli studies. METHOD: PubMed and PsychINFO were searched for quantitative
      pictorial food stimuli studies investigating healthy controls and expert
      diagnosed eating-disordered patients. RESULTS: Patients with eating disorders
      (ED) demonstrated cue reactivity to food stimuli. Results from functional imaging
      suggest sensory disengagement and higher emotional involvement while self
      reported data and facial EMG revealed that food pictures were perceived as less
      pleasurable. Different experimental paradigms have demonstrated an attentional
      bias for food cues in ED. Currently, psychophysiological data is widely
      inconclusive. DISCUSSION: Evidence suggests cue reactivity to food pictures in
      eating-disordered patients. However, the overall picture is inconclusive because
      methodological problems and the integration of findings from different
      experimental approaches pose a challenge to the research field.

PMID- 20127932
TI  - Night eating syndrome and weight loss outcome in obese patients.
AB  - OBJECTIVE: The clinical significance of diagnosing the night eating syndrome
      (NES) in obese individuals has not been clearly demonstrated. We aimed to test
      the effect of NES on weight loss outcome in obesity. METHOD: In an observational
      case-control study, we measured weight loss outcome in obese individuals with NES
      (32 cases) and 68 non-NES matched participants entering a weight-loss program.
      The diagnosis of NES was generated by a two-stage assessment, including the Night
      Eating Questionnaire (screening test) and the Night Eating Syndrome History and
      Inventory. The program included a 21-day inpatient treatment based on a low
      calorie diet, exercise, and psycho-educational groups, followed by a 6-month
      outpatient follow-up. Body weight, metabolic parameters, and questionnaires of
      psychopathology were assessed at baseline, at the end of the inpatient period and
      at the end of follow-up. RESULTS: NES participants were only characterized by
      significantly higher scores of the Beck Depression Inventory and the Night Eating
      Questionnaire. The time course of weight loss did not differ between groups
      throughout the study period. Only eight NES participants were still classified as
      NES at study end. DISCUSSION: The presence of NES does not affect weight loss
      outcome of an obesity treatment based on lifestyle modification.

PMID- 20127933
TI  - The refeeding syndrome and glucose load.
AB  - OBJECTIVE: A 10-year-old girl with anorexia nervosa developed the refeeding
      syndrome following cautious reintroduction of nutrition, emphasizing that even
      with cautious refeeding a shift in fluid, glucose, and electrolytes can still
      occur, increasing the risk of morbidity and mortality in this ever growing
      vulnerable group. METHOD: Biochemical, nutritional, and anthropometrical
      monitoring in the patient, who followed a conservative refeeding program after a
      prolonged period of nutritional inadequacy. RESULTS: The refeeding syndrome
      presented itself with hypophosphatemia, hypotension, and cardiac abnormalities
      whilst refeeding at 25 kcal/kg (600 kcal/day). DISCUSSION: Comprises of a
      literature review, highlighting this case as the youngest reported case of
      refeeding syndrome in anorexia nervosa. Discussion focuses on the possible
      deleterious affects that carbohydrates may have in exacerbating the refeeding
      syndrome.

PMID- 20127934
TI  - Polydipsia and hyponatremia in a woman with anorexia nervosa.
AB  - OBJECTIVE: Hyponatremia is infrequently reported in the constellation of
      metabolic abnormalities in patients with eating disorders. We sought to identify
      the etiology and describe the management of a patient with anorexia nervosa and
      hyponatremia. METHOD: We report the case of a 23-year-old woman with anorexia
      nervosa who suffered with severe hyponatremia. RESULTS: The etiology of
      hyponatremia in this case, as in most patients with eating disorders, was
      multifactorial, encompassing both hypovolemic and euvolemic categories of
      hyponatremia. Multiple impairments in the ability to clear free water are
      responsible for a heightened risk for hyponatremia in patients with anorexia
      nervosa. DISCUSSION: This case underscores the importance of careful scrutiny of
      fluid intake, an awareness of medications that lead to hyponatremia, and the need
      for regular monitoring of serum electrolytes, even in patients with anorexia
      nervosa, to allow for an early diagnosis and to assist in the formulation of an
      effective treatment and prevention strategy.

PMID- 20127935
TI  - Eating disorders in DSM-V: review of existing literature (Part 3).

PMID- 20127936
TI  - Rationale for the application of exposure and response prevention to the
      treatment of anorexia nervosa.
AB  - OBJECTIVE: Anorexia nervosa (AN) is a life threatening and difficult to treat
      illness with a high relapse rate. Current treatments are inadequate and new
      approaches to treatment are needed. METHOD: We review the data on anxiety in AN,
      the relationship between anxiety disorders and AN, and the use of Exposure and
      Response Prevention in treatment. RESULTS: The overlap between AN and anxiety
      disorders suggest a model of AN in which baseline anxiety features yield eating
      related fears, avoidance behaviors, and ritualized safety behaviors that promote
      the underweight state and the perpetuation of the disorder. We propose an
      Exposure and Response Prevention treatment to prevent relapse in AN. DISCUSSION:
      Overlap between AN and anxiety disorders suggests that Exposure and Response
      Prevention may be a new and beneficial approach to preventing relapse in
      individuals with AN.

PMID- 20127937
TI  - Mediators between perfectionism and eating disorder psychopathology: shape and
      weight overvaluation and conditional goal-setting.
AB  - OBJECTIVE: To examine mediators of the relationship between perfectionism and
      eating disorder (ED) psychopathology in a clinical sample. METHOD: Participants
      were 201 women with a DSM-IV diagnosed ED consecutively referred to a specialist
      outpatient treatment clinic. Participants completed measures of perfectionism, ED
      psychopathology, shape and weight overvaluation, and conditional goal-setting
      (CGS). RESULTS: Evaluation of a multivariate mediator model using Baron and
      Kenny's (1986) four-step mediation methodology showed that shape and weight
      overvaluation and CGS significantly and uniquely mediated the relation between
      self-oriented perfectionism (SOP) and restraint, eating concern, shape concern,
      and weight concern. The mediator model furthered the proportion of explained
      variance in outcomes beyond the direct effects model by 28-49%. DISCUSSION: The
      findings support the conclusion that the relationship between SOP and ED
      psychopathology in women with a clinically diagnosed ED is mediated by shape and
      weight overvaluation and CGS.

PMID- 20127939
TI  - Percent body fat is a risk factor for relapse in anorexia nervosa: a replication
      study.
AB  - OBJECTIVE: We aimed to replicate and extend our previous findings of an
      association between percent body fat in recently weight-restored patients with
      Anorexia Nervosa (AN) and clinical outcome in the year following treatment.
      METHOD: Twenty-two hospitalized, weight-restored women with AN underwent whole
      body MRI to determine percent adipose tissue. Following hospital discharge,
      patients were contacted regularly, and at the end of the year, clinical outcome
      was determined using modified Morgan-Russell (MR) criteria: full, good, fair or
      poor. Identical to our previous study, outcome was dichotomized into "full, good
      or fair" and "poor" groups. RESULTS: Data from 21 subjects were available for
      analysis. Percent body fat was significantly lower in the poor outcome group (22%
      +/- 5%) compared to the "full, good or fair" outcome group (27 % +/- 4%)(p <
      0.035). To further examine the relationship, we combined data from the current
      study with data from the 26 subjects on whom we had previously reported.
      Univariate analysis of variance (ANOVA) demonstrated a significant difference in
      percent adipose tissue across the four MR outcome groups (F = 3.416, df = 3,
      p<0.03). DISCUSSION: Lower percent adipose tissue after short-term weight
      normalization is associated with poor clinical outcome in the year following
      inpatient treatment. These findings may be important in the assessment of risk
      for relapse in patients with AN.

PMID- 20127938
TI  - Factors associated with binge eating disorder in pregnancy.
AB  - OBJECTIVE: To identify factors associated with incidence and course of broadly
      defined binge eating disorder (BED) in pregnancy. METHOD: As a part of the
      Norwegian Mother and Child Cohort Study (MoBa), 45,644 women completed a
      questionnaire at approximately 18 weeks of gestation. RESULTS: Incidence of BED
      was significantly associated with lifetime sexual abuse, lifetime physical abuse,
      lifetime major depression, symptoms of anxiety and depression, low life
      satisfaction, low self-esteem, low partner relationship satisfaction, smoking,
      alcohol use, lack of social support, and several weight-related factors.
      Continuation was negatively associated with thoughts of being overweight before
      pregnancy. Remission was positively associated with thoughts of being overweight
      before pregnancy and negatively associated with overvaluation of weight.
      DISCUSSION: Onset of BED in pregnancy was associated with psychological, social
      and weight-related factors, as well as health behaviors and adverse life events.
      In women with prepregnancy BED, thoughts of being overweight before pregnancy and
      overvaluation of weight were associated with course of BED during pregnancy.

PMID- 20127940
TI  - Use of mirtazapine in an adult with refractory anorexia nervosa and comorbid
      depression: a case report.
AB  - The objective of this report was to describe an efficacious treatment of an adult
      with long-standing anorexia nervosa (AN). A 50-year-old woman with an over 7-year
      history of AN and comorbid major depression had been treated unsuccessfully with
      numerous psychotropic medications, manualized cognitive behavior therapy, and an
      intensive outpatient treatment program before referral. After treatment with
      mirtazapine, she gained weight and her depression improved. A 9-month follow-up
      revealed a maintenance of these benefits. Mirtazapine may be useful for older,
      chronically ill patients presenting with AN and comorbid depression.

PMID- 20127941
TI  - The proof of the pudding is in the eating: is the DEBQ-external eating scale a
      valid measure of external eating?
AB  - OBJECTIVE: To test the construct validity and discriminative validity of the
      widely used Dutch Eating Behavior Questionnaire's (DEBQ) External Eating (EE)
      subscale. METHOD: After being exposed to food cues or not participants completed
      a bogus taste test. Subjective cue reactivity during food exposure and actual
      food intake after food exposure were measured. RESULTS: EE scores were unrelated
      to food intake. A robust main effect of food cue exposure was found but contrary
      to what was predicted, low EE scorers ate more after food cue exposure than
      without whereas high EE scorers did not. The actual eating behavior of high and
      low scorers on the other DEBQ subscales - emotional and restrained eating -
      demonstrated that the EE also lacks discriminative validity. DISCUSSION: The EE
      showed no predictive validity and no discriminative validity. The usefulness of
      the distinction of different types of concerned eaters is questioned.

PMID- 20127942
TI  - Demand-specific alteration of medial prefrontal cortex response during an
      inhibition task in recovered anorexic women.
AB  - OBJECTIVE: It is well known that individuals with anorexia nervosa (AN) are
      inhibited and over-controlled. This study investigated a prefrontal-cingulate
      network that is involved in inhibitory control. METHOD: To avoid the confounds of
      malnutrition, 12 recovered (RAN) subjects were compared to 12 matched control
      women (CW) using a validated inhibition task (i.e., a stop signal task) during
      functional magnetic resonance imaging. RESULTS: Consistent with the a priori
      hypothesis, RAN subjects showed altered task-related activation in the medial
      prefrontal cortex (mPFC), a critical node of the inhibitory control network.
      Specifically, whereas RAN and CW showed similar mPFC activity during trials when
      inhibitory demand was low (i.e., easy trials), RAN relative to CW showed
      significantly less mPFC activation as inhibition trials became more difficult
      (i.e., hard trials), suggesting a demand-specific modulation of inhibitory
      control circuitry in RAN. DISCUSSION: These findings support a neural basis for
      altered impulse control symptoms in AN.

PMID- 20127943
TI  - Rationale for the development of IMC-3G3, a fully human immunoglobulin G subclass
      1 monoclonal antibody targeting the platelet-derived growth factor receptor
      alpha.
AB  - A large body of evidence suggests that the platelet-derived growth factor (PDGF)
      family and associated receptors are potential targets in oncology therapeutic
      development because of their critical roles in the proliferation and survival of
      various cancers and in the regulation and growth of the tumor stroma and blood
      vessels. Several small molecules that nonspecifically target the PDGF signaling
      axis are in current use or development as anticancer therapies. However, for the
      majority of these agents, PDGF and its receptors are neither the primary targets
      nor the principal mediators of anticancer activity. IMC-3G3, a fully human
      monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the
      human PDGF receptor alpha (PDGFRalpha) with high affinity and blocks PDGF ligand
      binding and PDGFRalpha activation. The results of preclinical studies and the
      frequent expression of PDGFRalpha in many types of cancer and in cancer
      associated stroma support a rationale for the clinical development of IMC-3G3.
      Currently, IMC-3G3 is being evaluated in early clinical development for patients
      with several types of solid malignancies.

PMID- 20127944
TI  - Targeting FMS-related tyrosine kinase receptor 3 with the human immunoglobulin G1
      monoclonal antibody IMC-EB10.
AB  - FMS-related tyrosine kinase receptor 3 (FLT3) is a class III receptor tyrosine
      kinase that holds considerable promise as a therapeutic target in hematologic
      malignancies. Current efforts directed toward the development of small-molecule
      tyrosine kinase inhibitors of FLT3 may be limited by off-target toxicities and
      the development of drug resistance. Target-specific antibodies could overcome
      these hurdles and provide additional mechanisms to enhance the antitumor efficacy
      of FLT3 inhibitors. IMC-EB10 is a novel antibody directed against FLT3. The
      binding of IMC-EB10 to FLT3 results in antiproliferative effects in vitro and in
      mouse models engrafted with human leukemia cells that harbor wild-type or
      constitutively activated FLT3. Future clinical trials will test these notions
      formally and will identify the most appropriate opportunities for this member of
      a new generation of antileukemic therapies.

PMID- 20127945
TI  - Improving the efficacy of radioimmunotherapy for non-Hodgkin lymphomas.
AB  - Approximately 66,000 Americans develop non-Hodgkin lymphoma (NHL) each year.
      Although the use of unlabeled antibodies such as rituximab has significantly
      improved survival when combined with standard chemotherapy regimens,
      approximately two-thirds of lymphoma patients eventually develop disease
      recurrence and die of their disease. Novel treatments are urgently needed to cure
      these patients. One strategy involves the use of radiolabeled immunoconjugates
      that specifically localize radiation delivery to sites of lymphoma while
      minimizing toxicity to normal tissues. A growing number of studies support the
      contention that radiolabeled antibody therapy can improve overall survival of
      lymphoma patients and lead to durable remissions, with probable cures, in many
      patients. Various approaches for enhancing the effectiveness of
      radioimmunoconjugates have been studied, including: use in newly diagnosed
      lymphoma patients, combination with chemotherapy or other monoclonal antibodies,
      use with hematopoietic stem cell transplantation, multistep pretargeting
      strategies to further minimize toxicity, and simultaneous targeting of multiple B
      cell antigens. This article summarizes the current knowledge supporting the use
      of radioimmunotherapy, an underused but effective treatment modality in NHL
      patients.

PMID- 20127946
TI  - Introduction to the supplement, "Cancer Therapy with Antibodies and
      Immunoconjugates".
AB  - This supplement includes 16 representative articles presented at the 12th
      Conference on Cancer Therapy With Antibodies and Immunconjugates, Parsippany, New
      Jersey, October 16-18, 2008, encompassing cancer treatment with unconjugated and
      isotope-conjugated antibodies targeting selective cancer biomarkers.

PMID- 20127948
TI  - Vascular endothelial growth factor receptor-1 in human cancer: concise review and
      rationale for development of IMC-18F1 (Human antibody targeting vascular
      endothelial growth factor receptor-1).
AB  - The human vascular endothelial growth factor receptor-1 (VEGFR-1, or Flt-1) is
      widely expressed in normal and pathologic tissue and contributes to the
      pathogenesis of both neoplastic and inflammatory diseases. In human cancer, VEGFR
      1 mediated signaling is responsible for both direct tumor activation and
      angiogenesis. VEGFR-1 mediated activation of nonmalignant supporting cells,
      particularly stromal, dendritic, hematopoietic cells, and macrophages, is also
      likely important for cancer pathogenesis. VEGFR-1 is also hypothesized to enable
      the development of cancer metastases by means of activation and premetastatic
      localization in distant organs of bone marrow-derived hematopoietic progenitor
      cells, which express VEGFR-1. IMC-18F1 is a fully human IgG(1) antibody that
      binds to VEGFR-1 and has been associated with the inhibition of cancer growth in
      multiple in vitro and human tumor xenograft models. The preliminary results of
      phase 1 investigations have also indicated a favorable safety profile for IMC
      18F1 at doses that confer antibody concentrations that are associated with
      relevant antitumor activity in preclinical models.

PMID- 20127949
TI  - High-dose radioimmunotherapy combined with extracorporeal depletion in a
      syngeneic rat tumor model: evaluation of toxicity, therapeutic effect, and tumor
      model.
AB  - BACKGROUND: The aim of the current study was to investigate the possibility of
      increasing the maximal tolerated dose (MTD) of a tumor-selective radiolabeled
      antibody when radioimmunotherapy (RIT) is combined with extracorporeal depletion
      of radioimmunoconjugates from the circulation. Furthermore, the authors evaluated
      whether this increase in dose improved the therapeutic effect on solid manifest
      tumors in an immunocompetent animal model. METHODS: Rats were injected with high
      activities/body weight of lutetium ((177)Lu)- or yttrium ((90)Y)-labeled antibody
      conjugates (monoclonal antibody tetraazacyclododecanetetraacetic acid-biotin) and
      subjected to removal of the conjugate from the circulation by extracorporeal
      affinity adsorption treatment 24 hours postinjection. Myelotoxicity was assessed
      by analysis of blood parameters for 12 weeks. The effect of increased doses in
      combination with extracorporeal affinity adsorption treatment was evaluated with
      respect to myelotoxicity and therapeutic effect in a syngeneic rat colon cancer
      model. RESULTS: The MTD of (177)Lu- or (90)Y-labeled immunoconjugates could be
      increased 2.0x or 1.5x, respectively, when RIT was combined with extracorporeal
      affinity adsorption treatment. All animals treated with (177)Lu- or (90)Y-labeled
      antibodies showed persistent complete response of manifest tumors (approximately
      10 x 15 mm) within 16 days postinjection. However, several animals showed
      disseminated disease 1.5 to 3 months postinjection. CONCLUSIONS: Extracorporeal
      affinity adsorption treatment is a method that safely and efficiently reduces
      myelotoxicity associated with RIT. Extracorporeal affinity adsorption treatment
      allows increased administered activity without increased toxicity, with the aim
      of increasing the absorbed dose to the tumor. However, because tumor/normal
      tissue radiosensitivity ratios are more favorable in rodents, it is not possible
      to draw any conclusions concerning the therapeutic efficacy of increased
      administered activity in combination with extracorporeal affinity adsorption
      treatment in this study. Targeted RIT with beta-emitting radionuclides seems not
      to be effective in microscopic disease, because metastases developed at sites
      without previously known disease.

PMID- 20127947
TI  - Improving the treatment of non-Hodgkin lymphoma with antibody-targeted
      radionuclides.
AB  - Radioimmunotherapy of non-Hodgkin lymphoma comprises a (90)Y- or (131)I-labeled
      murine anti-CD20 IgG, but both agents also include a substantial dose of
      unlabeled anti-CD20 IgG given immediately before the radioconjugate to reduce its
      uptake in the spleen (primary normal B-cell antigen sink); this extends its
      plasma half-life and improves tumor visualization. Thus, these treatments combine
      an effective anti-CD20 radioconjugate with an unconjugated anti-CD20 antibody
      that is also therapeutically active, but the large anti-CD20 IgG predose (
      approximately 900 mg) may diminish the tumor localization of the
      radioimmunoconjugate (eg, 10-35 mg). We have examined alternative approaches that
      enhance radionuclide targeting and improve antitumor responses. One uses a (90)Y
      labeled anti-CD22 IgG (epratuzumab) combined with an antibody therapy regimen of
      a humanized anti-CD20 IgG (veltuzumab). Pretargeted radionuclide therapy using a
      trivalent, humanized, recombinant bispecific anti-CD20 antibody with a (90)Y
      hapten-peptide is another highly effective method that is also less toxic than
      directly radiolabeled IgG. Finally, all approaches benefit from the addition of a
      consolidation-dosing regimen of the anti-CD20 IgG antibody. This article reviews
      these various options and discusses how some fundamental changes could
      potentially enhance the response and duration from radionuclide-targeted therapy.

PMID- 20127950
TI  - Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse
      model of medullary thyroid carcinoma.
AB  - BACKGROUND: Significant antitumor effects were previously observed with
      radioimmunotherapy (RIT) using an anti-carcinoembryonic antigen (CEA) monoclonal
      antibody (F6) labeled with iodine-131 in medullary thyroid cancer (MTC)-bearing
      nude mice. Nevertheless, no complete response was achieved. Because angiogenesis
      is critical for tumor growth, bevacizumab is used to treat solid tumor in
      clinical practice. The present pilot study evaluated toxicity and efficacy of RIT
      combined with bevacizumab in mice subcutaneously grafted with TT MTC cells.
      METHODS: Groups of 4-6 nude mice were treated with 5 microg/g bevacizumab twice
      weekly during 4 weeks and/or 100 MBq of (131)I-F6. For combined therapy,
      bevacizumab was given at Day 0 followed by (131)I-F6 at Day 30. The control group
      received no treatment. Animal weight, hematological toxicity, tumor volume, and
      serum calcitonin were monitored for 2 or 4 months. RESULTS: Bevacizumab alone
      induced no cytopenia and no significant weight loss. A weight loss of 12 +/- 1%
      and 15 +/- 2% was observed in mice treated by RIT alone or bevacizumab + RIT,
      respectively. RIT alone and combined treatment induced leukopenia and anemia. RIT
      alone and RIT plus bevacizumab induced tumor responses with minimum relative
      tumor volume of 0.38 +/- 0.24 and 0.15 +/- 0.07%, respectively, and time to
      progression of 35 +/- 5 and 56 +/- 11 days, respectively. CONCLUSIONS:
      Pretreatment with bevacizumab improved RIT efficacy, with similar toxicity as
      compared as RIT alone.

PMID- 20127951
TI  - Improved efficacy of alpha-particle-targeted radiation therapy: dual targeting of
      human epidermal growth factor receptor-2 and tumor-associated glycoprotein 72.
AB  - BACKGROUND: Human epidermal growth factor receptor-2 (HER-2) and tumor-associated
      glycoprotein 72 (TAG-72) have proven to be excellent molecular targets for cancer
      imaging and therapy. Trastuzumab, which binds to HER-2, is effective in the
      treatment of disseminated intraperitoneal disease when labeled with (213)Bi or
      (212)Pb. (213)Bi-humanized CC49 monoclonal antibody (HuCC49DeltaCH2), which binds
      to TAG-72, inhibits the growth of subcutaneous xenografts. A next logical step to
      improve therapeutic benefit would be to target tumors with both molecules
      simultaneously. METHODS: Athymic mice bearing intraperitoneal human colon
      carcinoma xenografts were treated with a combination of trastuzumab and
      HuCC49DeltaCH2 labeled with (213)Bi administered through an intraperitoneal
      route. The sequence of administration also was examined. RESULTS: Before
      combining the 2 monoclonal antibodies, the effective doses of (213)Bi
      CC49DeltaCH2 and (213)Bi-trastuzumab for the treatment of peritoneal disease were
      determined to be 500 muCi for each labeled antibody. Treatment with (213)Bi
      HuCC49DeltaCH2 resulted in a median survival of 45 days and was comparable to the
      median survival achieved with (213)Bi-trastuzumab. Each combination provided
      greater therapeutic efficacy than either of the agents given alone. However, the
      greatest therapeutic benefit was achieved when (213)Bi-HuCC49DeltaCH2 and (213)Bi
      trastuzumab were coinjected, and a median survival of 147 days was obtained.
      CONCLUSIONS: Dual targeting of 2 distinct molecules in tumors such as TAG-72 and
      HER-2 with alpha-particle radiation resulted in an enhanced, additive,
      therapeutic benefit. The authors also observed that this radioimmunotherapeutic
      strategy was well tolerated.

PMID- 20127952
TI  - Pretargeted radioimmunotherapy in rapidly progressing, metastatic, medullary
      thyroid cancer.
AB  - Medullary thyroid cancer (MTC) patients with localized residual disease and/or
      distant metastases may survive for several years or rapidly progress and die of
      their disease. Thus, highly reliable prognostic factors are needed for an early
      distinction between high-risk patients who need to be treated and low-risk
      patients who warrant a watch-and-wait approach. Calcitonin doubling time is an
      independent predictor of survival, with a high predictive value in a population
      of patients who have not normalized their calcitonin, even after repeated
      surgery. Several imaging methods should be proposed for patients with abnormal
      residual calcitonin levels persisting after complete surgery: ultrasonography and
      computed tomography (CT) for neck exploration, and CT for chest, abdomen, and
      pelvis. Magnetic resonance imaging (MRI) appears to have an advantage over CT for
      the detection of liver metastases from endocrine tumors. Moreover, MRI appears to
      be a sensitive imaging technique for detecting the spread of MTC to bone/bone
      marrow. 2-Fluoro-2-deoxy-D-glucose positron emission tomography/CT could be used
      for staging patients with progressive MTC, with possible prognostication by
      standard uptake value quantification. For systemic treatment of patients with
      rapidly progressing metastatic MTC, chemotherapy is not considered a valid
      therapeutic option. It is too early to evaluate the potential effectiveness of
      multikinase inhibitors, although interesting results of phase 2 studies have
      shown a transient stabilization in 30% to 50% of patients. Pretargeted
      radioimmunotherapy has been the only innovative treatment modality convincingly
      showing some survival benefit when compared with a historical untreated control
      group.

PMID- 20127953
TI  - In vitro evaluation of avidin antibody pretargeting using 211At-labeled and
      biotinylated poly-L-lysine as effector molecule.
AB  - BACKGROUND: Pretargeting is an approach for enhancing the therapeutic index of
      radioimmunotherapy by separating the administrations of tumor-targeting substance
      and radiolabel. In this study, a pretargeting model system of avidin-conjugated
      monoclonal antibody trastuzumab and biotinylated, (211)At-labeled poly-L-lysine
      was constructed and analyzed in vitro. METHODS: Avidin activated by 4-(N
      maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester
      sodium salt (sulfo-SMCC) and thiolated trastuzumab were incubated overnight at 4
      degrees C. The monomeric fraction was extracted using size exclusion fast protein
      liquid chromatography (FPLC) and further purified on an iminobiotin affinity
      column. Poly-L-lysine was biotinylated with succinimidyl-6-(biotinamido)hexanoate
      (NHS-LC-biotin), followed by direct (211)At-labeling with N-succinimidyl-3
      (trimethylstannyl)benzoate (m-MeATE), and succinylation with succinic anhydride.
      The avidin-trastuzumab conjugate was characterized by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and FPLC, together with cell-binding and
      biotin-binding analyses. The labeled poly-L-lysine conjugate was assessed in
      terms of radiochemical purity and avidin binding. Furthermore, the full
      pretargeting system was evaluated in a tumor cell binding assay. RESULTS: The
      estimated size of the pretargeting molecule was 220 kDa, which corresponds to
      that of the expected avidin-trastuzumab monomer. Neither cell-binding ability
      (64%) nor biotin-binding ability (85%-95%) indicated any severe adverse effects
      from the chemical modifications. The radiochemical purity of the effector
      molecule was 92%-97%, and the avidin binding capacity was 91%-93%. The complete
      pretargeting assay resulted in a binding of 75.3 +/- 6.2% of added effector
      molecules to cells. CONCLUSIONS: The high binding of effector molecules to cells
      demonstrates a proof of concept for the synthesized molecules and pretargeting
      system, which will be further evaluated in vivo in future studies.

PMID- 20127954
TI  - Toxicity-reducing potential of extracorporeal affinity adsorption treatment in
      combination with the auristatin-conjugated monoclonal antibody BR96 in a
      syngeneic rat tumor model.
AB  - BACKGROUND: Antibody-drug conjugates, comprising monoclonal antibodies (MoAbs)
      that bind to tumor-associated antigens, display different toxicity profiles
      compared with radiolabeled MoAbs. Dose-limiting toxicities may include damage to
      the liver and myelotoxicity. The drug component is the antimitotic agent
      auristatin, which is 100-1000 times more potent than doxorubicin. Consequently,
      auristatin antibody-drug conjugates require a high selectivity in tumor targeting
      to display pronounced activity at well-tolerated doses. We have evaluated the
      possibility of increasing the therapeutic index of BR96-auristatin by combining
      the administration of conjugates with subsequent extracorporeal affinity
      adsorption treatment. METHODS: Rats were injected with biotinylated, monomethyl
      auristatin F (MMAF)-conjugated monoclonal antibody BR96. The conjugate was then
      removed from the circulation by extracorporeal affinity adsorption treatment, 24
      hours postinjection using an avidin affinity column. By analyzing blood
      parameters for 100 days, myelotoxicity, hepatotoxicity, and nephrotoxicity were
      assessed. Body weight, general status, and tumor size were also recorded. The
      toxicity-reducing effect of extracorporeal affinity adsorption treatment was
      evaluated. RESULTS: Extracorporeal affinity adsorption treatment removed 85%-90%
      of BR96-MMAF from the circulation. Early toxicity-related death was seen in
      nontumor-bearing animals that were given MMAF-conjugated BR96, in contrast to
      animals that were given a higher amount of BR96-MMAF with subsequent
      extracorporeal affinity adsorption treatment, in which all survived 100 days
      postinjection. Extracorporeal affinity adsorption treatment reduced the loss of
      body weight, myelotoxicity, and hepatotoxicity. CONCLUSIONS: Extracorporeal
      affinity adsorption treatment can be used to reduce the toxicity associated with
      administration of BR96-MMAF conjugates, making it possible to increase the amount
      of conjugates administered. The combined treatment will be further optimized in
      future studies.

PMID- 20127955
TI  - The influence of proteasome inhibitor MG132, external radiation, and unlabeled
      antibody on the tumor uptake and biodistribution of (188)re-labeled anti-E6 C1P5
      antibody in cervical cancer in mice.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is considered a necessary step
      for the development of cervical cancer, and >95% of all cervical cancers have
      detectable HPV sequences. The authors of this report recently demonstrated the
      efficacy of radioimmunotherapy (RIT) targeting viral oncoprotein E6 in the
      treatment of experimental cervical cancer. They hypothesized that the
      pretreatment of tumor cells with various agents that cause cell death and/or
      elevation of E6 levels would increase the accumulation of radiolabeled antibodies
      to E6 in cervical tumors. METHODS: HPV type 16 (HPV-16)-positive CasKi cells were
      treated in vitro with up to 6 grays of external radiation, or with the proteasome
      inhibitor MG-132, or with unlabeled anti-E6 antibody C1P5; and cell death was
      assessed. The biodistribution of (188)Re-labeled C1P5 antibody was determined in
      both control and radiation MG-132-treated CasKi tumor-bearing nude mice. RESULTS:
      (188)Re-C1P5 antibody demonstrated tumor specificity, very low uptake, and fast
      clearance from the major organs. The amount of tumor uptake was enhanced by MG
      132 but was unaffected by pretreatment with radiation. In addition, in vitro
      studies demonstrated an unanticipated effect of unlabeled antibody on the amount
      of cell death, a finding that was suggested by the authors' previous in vivo
      studies in a CasKi tumor model. CONCLUSIONS: The current results indicated that
      pretreatment of cervical tumors with the proteasome inhibitor MG-132 and with
      unlabeled antibody to E6 can serve as a means to generate nonviable cancer cells
      and to elevate the levels of target oncoproteins in the cells for increasing the
      accumulation of targeted radiolabeled antibodies in tumors. These results favor
      the further development of RIT for cervical cancers targeting viral antigens.

PMID- 20127957
TI  - 177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated
      neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic
      strategy.
AB  - BACKGROUND: (177)Lu-(DOTA0,Tyr3) octreotate is a new treatment modality for
      disseminated neuroendocrine tumors. According to a consensus protocol, the
      calculated maximally tolerated absorbed dose to the kidney should not exceed 27
      Gy. In commonly used dosimetry methods, planar imaging is used for determination
      of the residence time, whereas the kidney mass is determined from a computed
      tomography (CT) scan. METHODS: Three different quantification methods were used
      to evaluate the absorbed dose to the kidneys. The first method involved common
      planar activity imaging, and the absorbed dose was calculated using the medical
      internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For
      this method, 2 region of interest locations for the background correction were
      investigated. The second method also included single-photon emission computed
      tomography (SPECT) data, which were used to scale the amplitude of the time
      activity curve obtained from planar images. The absorbed dose was calculated as
      in the planar method. The third method used quantitative SPECT images converted
      to absorbed dose rate images, where the median absorbed dose rate in the kidneys
      was calculated in a volume of interest defined over the renal cortex. RESULTS:
      For some patients, the results showed a large difference in calculated kidney
      absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods
      generally gave consistent values, although the calculations were based on
      different assumptions. Dosimetry using the baseline planar method gave higher
      absorbed doses in all patients. The values obtained from planar imaging with a
      background region of interest placed adjacent to the kidneys were more consistent
      with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the
      first 2 of the 4 planned therapy cycles made the major contribution. CONCLUSIONS:
      The results suggested that patients evaluated according to the conventional
      planar-based dosimetry method may have been undertreated compared with the other
      methods. Hematology and creatinine did not indicate any restriction for a more
      aggressive approach, which would be especially useful in patients with more
      aggressive tumors where there is not time for more protracted therapy.

PMID- 20127958
TI  - Three methods assessing red marrow dosimetry in lymphoma patients treated with
      radioimmunotherapy.
AB  - BACKGROUND: Maximum injected activity in radioimmunotherapy (RIT) is limited by
      bone marrow toxicity. Many dosimetric approaches have been proposed, leading to
      high variability in the results and elusive absorbed dose-effect relations. This
      study presents the results of red marrow (RM) absorbed dose estimates performed
      with 3 methods. METHODS: Five patients received 2 co-infusions of (90)Y-labeled
      (370 MBq/m2) and (111)In- labeled (120 MBq) epratuzumab (1.5 mg/kg) 1 week apart.
      RM-absorbed dose was estimated by 3 methodologies. The first approach (M1) used
      L(2)-L(4) lumbar vertebrae imaging. M2 and M3 methods used different red marrow
      to blood ratios (RMBLR) to assess RM-absorbed dose. RMBLR was set to a fixed
      value of 0.36 in M2 or assessed according to each patient's hematocrit in M3.
      RESULTS: Median RM-absorbed doses were 4.1 (2.9-8.4), 2.3 (2.0-2.7), and 2.3 (1.6
      2.5) mGy/MBq for M1, M2, and M3, respectively. No trend could be found between
      total RM-absorbed dose and toxicity for M2 and M3. Conversely, M1 seemed to
      provide the best absorbed dose-effect relation. The 4 patients with the highest
      RM-absorbed doses exhibited grade 4 toxicity. The fifth patient, with the lowest
      RB absorbed dose, exhibited only a mild (grade 2) toxicity. CONCLUSIONS: Image
      based methodology (M1) seems to better predict hematological toxicity as compared
      with blood-based methods. Only this method provides for bone marrow involvement.

PMID- 20127956
TI  - Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate
      cancer.
AB  - Despite recent advances, advanced prostate cancer is suboptimally responsive to
      current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that
      targets prostate-specific membrane antigen (PSMA) shows promise and is an area of
      active investigation. J591 is a deimmunized IgG monoclonal antibody developed to
      target the extracellular domain of PSMA. Preclinical and early phase clinical
      studies using radiolabeled J591 have demonstrated efficacy in targeting tumor
      cells and decreasing levels of prostate-specific antigen. Radiolabeled J591 is
      well-tolerated, nonimmunogenic, and can be administered in multiple doses. The
      dose-limiting toxicity is reversible myelosuppression with little nonhematologic
      toxicity. Future studies will include approaches to optimize patient selection
      and incorporate novel strategies to improve the success of anti-PSMA
      radioimmunotherapy.

PMID- 20127959
TI  - Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer
      using a bispecific anticarcinoembryonic antigen CEA X anti-di
      diethylenetriaminepentaacetic acid F(ab')2 antibody.
AB  - BACKGROUND: Antibody-based imaging agents are available commercially, but their
      success has been limited, mainly because of low contrast and the emergence of 2
      fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scanning. In
      pretargeting, administration of the radionuclide is separated from the antibody,
      thereby enhancing image contrast and allowing detection at earlier time points
      after injection. METHODS: The authors conducted an open-label, single-arm trial
      that assessed a pretargeting procedure in which an anticarcinoembryonic antigen x
      (anti-CEA x) anti-diethylenetriaminepentaacetic acid (anti-DTPA)-indum (In)
      antibody was used in combination with a (111)In-labeled di-DTPA peptide for the
      diagnostic imaging of CEA-expressing colorectal cancer. Three patients received
      the (111)In peptide alone to investigate tumor targeting, organ distribution, and
      clearance of the peptide. Thereafter, 11 patients received the bispecific
      antibody (bsAb) (5 mg) to pretarget the tumor. After 3 to 5 days, patients were
      injected with 185 megabecquerels of (111)In-labeled peptide to assess the optimal
      interval for best image quality. RESULTS: Fourteen patients with primary
      colorectal cancer were enrolled. One of 3 patients who received (111)In peptide
      alone had low-level tumor uptake. In 9 of 11 other patients, tumors were
      observed. In 1 patient, FDG-PET-positive lymph nodes were observed clearly with
      pretargeted immunoscintigraphy. Peptide pharmacokinetics revealed enhanced
      circulating levels of (111)In-labeled peptide in patients in the 3-day interval
      cohort compared with the other cohorts. Tumor-to-background ratios ranged from
      3.5 to 6.4 in the 3-day interval group, from 5.1 to 14.2 in the 4-day interval
      group, and from 3.5 to 3.9 in the 5-day interval group. The best images were
      acquired with a 4-day interval at 24 hours after injection of the radiolabeled
      peptide. Grade 1 adverse events were observed in 2 patients. CONCLUSIONS: Imaging
      of colorectal cancer using a 2-step, pretargeting system produced the best
      imaging results 24 hours after peptide administration using a 4-day interval
      between injection of the bsAb and the peptide.

PMID- 20127960
TI  - Immature animals have higher cellular density in the healing anterior cruciate
      ligament than adolescent or adult animals.
AB  - There has been recent interest in the biologic stimulation of anterior cruciate
      ligament (ACL) healing. However, the effect of age on the ability of ligaments to
      heal has not yet been defined. In this study, we hypothesized that skeletal
      maturity would significantly affect the cellular and vascular repopulation rate
      of an ACL wound site. Skeletally Immature (open physes), Adolescent (closing
      physes), and Adult (closed physes) Yucatan minipigs underwent bilateral ACL
      transection and suture repair using a collagen-platelet composite. The response
      to repair was evaluated histologically at 1, 2, and 4 weeks. All three groups of
      animals had completely populated the ACL wound site with fibroblasts at 1 week.
      The Immature animals had a higher cellular density in the wound site than the
      Adult animals at weeks 2 and 4. Cells in the Immature ligament wounds were larger
      and more ovoid than in the Adult wounds. There were no significant differences in
      the vascular density in the wound site. Animal age had a significant effect on
      the density of cells populating the ACL wound site. Whether this observed
      cellular difference has an effect on the later biomechanical function of the
      repaired ACL requires further study.

PMID- 20127961
TI  - Factors facilitating research: a survey of zoo and aquarium professionals.
AB  - The purpose of this survey was to assess the background, training, and
      perceptions of professionals conducting and coordinating research at North
      American zoos and aquariums accredited by the Association of Zoos and Aquariums
      (AZA) and to identify the factors they considered critical to successful
      scientific programs. We analyzed responses to a 57-item questionnaire from 231
      professionals at AZA zoos and aquariums. The majority of those surveyed conducted
      behavioral research, conducted research only in a captive setting, held
      curatorial positions, had their salaries supported by their institutions'
      operating budget, and considered themselves part of a successful scientific
      program. About 30% of those we surveyed possessed a doctoral research degree in
      comparison to 55% possessing lesser level degrees-19% with master's, 34% with
      bachelor's, and 2% with other degrees. Support from the chief executive officer
      and personnel dedicated to conducting scientific programs were judged as the two
      most important factors contributing to the successful scientific programs. The
      information provided in this report may be used to develop and improve both
      established and newly initiated scientific programs in zoos and aquariums.

PMID- 20127962
TI  - Asian Americans' lay beliefs about depression and professional help seeking.
AB  - Guided by a culturally informed illness representation self-regulation model
      (CIRSRM), this study analyzed the relations among 223 Asian Americans' lay
      beliefs about depression, enculturation to Asian values, and their likelihood of
      seeking professional help for depression. Participants' lay beliefs were assessed
      through an analysis of written responses to open-ended questions about
      depression. Enculturation as well as beliefs in biological causes, situational
      causes, and a short duration of depression were significantly related to the
      likelihood of professional help seeking. In addition, enculturation moderated the
      association between several lay beliefs and the endorsement of professional help
      seeking. The findings are discussed in light of how clinicians can incorporate
      mental illness lay beliefs in their work with Asian Americans.

PMID- 20127963
TI  - Allonursing in captive belugas (Delphinapterus leucas).
AB  - This study describes allonursing (females nursing offspring that are not their
      own) in captive belugas (Delphinapterus leucas). In addition to the calf's
      mother, two females that were not pregnant or nursing at the time of the calf's
      birth spontaneously lactated and nursed the male calf intermittently throughout
      34 months of his life at the Vancouver Aquarium Marine Science Center. These
      observations suggest that allonursing may also take place in their wild
      counterparts and add to existing evidence of alloparental care in this species.
      Alloparental care, the care of nonoffspring, has been observed in every major
      mammalian taxon; the protection of calves through alloparental care may be a
      strong evolutionary benefit.

PMID- 20127964
TI  - On discovering relevant scales in surface roughness measurement--an evaluation of
      a band-pass method.
AB  - When characterizing surfaces and searching for correlations to functional
      properties, such as friction, finding the right scale of roughness for evaluation
      can improve correlations. However, in traditional roughness parameter analysis, a
      wide range of scales, or all scales of topography in the surface roughness
      measurements are evaluated together. In this study a multi-scale method using a
      series of band-pass filters is employed for finding scales of topography with
      strong correlations to friction.

PMID- 20127965
TI  - Further observations on the empty "amnion sign".
AB  - OBJECTIVE: To assess the positive predictive value of the empty "amnion sign"
      (visualization of an amnion without concomitant visualization of an embryo) for
      the diagnosis of early pregnancy failure. METHODS: Retrospective study of 882 1st
      trimester sonographic examinations with abnormal findings among women who were
      threatening to abort. Eight hundred six met the inclusion criteria. RESULTS: In
      the study cohort 286 (35.5%) had no identifiable embryo and 71 of those without
      an identifiable embryo had a visible amnion (24.8%). The breakdown of the mean
      sac diameter of the study cohort was as follows: those measuring less than 16 mm
      (n = 16); those measuring 16-20 mm (n = 20); those measuring 21 mm or more (n =
      35). Sixty-eight of the 71 patients had adequate follow-up. Pregnancy failure was
      confirmed in all 68 patients (positive predictive value = 100%). CONCLUSIONS: The
      data from this study indicate that visualization of an amnion without concomitant
      visualization of an embryo (the empty "amnion sign") confirms pregnancy failure
      regardless of the mean sac diameter and with a sufficiently high positive
      predictive value to make a definitive diagnosis.

PMID- 20127966
TI  - Reliability study of the sonographic measurement of the acromiohumeral distance
      in symptomatic patients.
AB  - BACKGROUND: The purpose of this study was to evaluate the inter- and intra
      observer reliability and accuracy of sonographic (US) acromiohumeral distance
      (AHD) measurement for both experienced and novice operators in US in patients
      suffering from subacromial impingement syndrome. METHOD: A total of 43 patients
      (50 shoulders) diagnosed with subacromial impingement syndrome were recruited
      from an orthopedic outpatient clinic. The US measurement of AHD was obtained
      consecutively in a neutral position and in a 60 degrees abduction position. A
      total of 300 blinded measurements were taken. RESULT: In the neutral abduction
      group the intra- observer interclass correlation coefficient (ICC) was 0.94 for
      the experienced operator and 0.92 for the novice operator. The inter-observer ICC
      was 0.70 and the accuracy was 1.1 mm. In the 60 degrees abduction group, the
      intra-observer ICC was 0.90 for the experienced operator and 0.87 for the novice
      operator. The inter-observer ICC was 0.64 and the accuracy was 1.4 mm. All ICCs
      were significant at a level of p < 0.0001. CONCLUSION: The inaccuracy of the
      method was 1 mm regardless of the experience of the observer. US AHD measurement
      in patients with shoulder complaints is not as accurate as reported in healthy
      subjects. This may have important implications for the clinical use of this
      parameter.

PMID- 20127967
TI  - Color Doppler sonographic evaluation of flow volume of the internal carotid and
      vertebral arteries after carotid endarterectomy.
AB  - BACKGROUND: To measure by Doppler sonography the blood flow volume (BFV) of the
      ipsilateral and contralateral extracranial internal carotid arteries (ICAs) and
      both vertebral arteries (VAs) before and after a carotid endarterectomy (CEA) of
      the ICA. We correlated the result with the degree of stenosis of the ICA. METHOD:
      One hundred seven patients who had a CEA were divided into 2 groups. Group I
      consisted of subjects with stenosis of ipsilateral ICA of >or=70% to near
      occlusion and Group II included subjects with near occlusion. The Doppler
      sonographic examinations were performed 1 day before the CEA, 7 days after the
      CEA, and 1 month after the CEA. The peak systolic velocity, end-diastolic
      velocity, time-averaged maximum blood flow velocity, resistance index of the
      ipsilateral ICA, and the BFV of both ICAs and both VAs were calculated. RESULT:
      There was a significant increase in the peak systolic velocity, maximum blood
      flow velocity, and the BFV of the ipsilateral ICA after the CEA. The BFV of the
      contralateral ICA and both VAs were not significantly altered after the CEA in
      both groups. CONCLUSION: The main CEA hemodynamic effect was an increase in the
      BFV of the ipsilateral ICA regardless of the degree of stenosis.

PMID- 20127969
TI  - IgG-lambda plasma cell myeloma with cytoplasmic azurophilic inclusion bodies.

PMID- 20127971
TI  - The Roche Cancer Genome Database (RCGDB).
AB  - Sequence variations are being studied for a better understanding of the mechanism
      and development of cancer as a mutation-driven disease. The systematic sequencing
      of genes in tumors and technological advances in high-throughput techniques
      combined with efficient data acquisition methods have resulted in an explosion of
      available cancer genome-related data. Despite the technological progress and
      increase of data, improvements in the application area, for example, drug target
      discovery, have failed to keep pace with increased research and development
      spending. One reason for this discrepancy is the ever increasing number of
      databases and the absence of a unified access to the mutation data. Currently,
      researchers typically have to browse several, often highly specialized databases
      to obtain the required information. A more complete understanding of relations
      and dependencies between mutations and cancer, however, requires the availability
      of an efficient integrative cancer genome information system. To facilitate this,
      we developed the Roche Cancer Genome Database (RCGDB), a freely available
      biological information system integrating different kinds of mutation data. The
      database is the first comprehensive integration of disparate cancer genome data
      like single nucleotide variants, single nucleotide polymorphisms, and chromosomal
      aberrations (CGH and FISH). RCGDB is freely accessible via a Google-like Web
      interface at http://rcgdb.bioinf.uni-sb.de/MutomeWeb/.

PMID- 20127972
TI  - Effect of pro-inflammatory and immunoregulatory cytokines on human tenocytes.
AB  - Tendon injury induces a local inflammatory response, characterized by the
      induction of pro-inflammatory cytokines. The aim of the present study was to
      analyze the effects of TNFalpha, IL-6 and IL-10 on key parameters of tendon
      homeostasis. Cultured primary human tenocytes were treated with the recombinant
      cytokines IL-6, IL-10, TNFalpha, or combinations of TNFalpha with IL-6 and IL-10
      (10 ng/mL, 6, 24 h). Expression of type I collagen, elastin, MMP-1, TNFalpha, IL
      1beta, IL-6, IL-10, and suppressors of cytokine signaling (SOCS1, 3) was analyzed
      with the use of RTD-PCR, immunocytochemistry, and Western blot analysis. In
      response to TNFalpha, tenocytes reduced their type I collagen deposition but
      increased their elastin gene expression and highly upregulated their expression
      for MMP-1, pro-inflammatory (TNFalpha, IL-1beta) and immunoregulatory (IL-6, IL
      10) cytokines. TNFalpha stimulation augmented SOCS1, whereas SOCS3 expression in
      tenocytes was also induced by IL-6. The treatment of tenocytes with IL-6 and IL
      10 had no effect on cytokine expression. Neither IL-6 nor IL-10 modulated the
      observed effects of TNFalpha significantly. These results indicate that TNFalpha
      strongly activates the tenocytes to amplify their own TNFalpha expression and,
      subsequently, that of other regulatory cytokines and matrix degrading enzymes.
      However, the impact of IL-6 and IL-10 on tenocytes remains unclear.

PMID- 20127973
TI  - Quantifying the effect of sequence variation on regulatory interactions.
AB  - The increasing amount of sequence data provides new opportunities and challenges
      to derive mechanistic models that can link sequence variations to phenotypic
      diversity. Here we introduce a new computational framework to suggest possible
      consequences of sequence variations on regulatory networks. Our method, called
      sTRAP (strap.molgen.mpg.de), analyses variations in the DNA sequence and predicts
      quantitative changes to the binding strength of any transcription factor for
      which there is a binding model. We have tested the method against a set of known
      associations between SNPs and their regulatory consequences. Our predictions are
      robust with respect to different parameters and model assumptions. Importantly we
      set an objective and quantifiable benchmark against which future improvements can
      be compared. Given the good performance of our method, we developed a publicly
      available tool that can serve as an important starting point for routine analysis
      of disease-associated sequence regions.

PMID- 20127974
TI  - Impact of next generation sequencing: the 2009 Human Genome Variation Society
      Scientific Meeting.
AB  - The annual scientific meeting of the Human Genome Variation Society (HGVS) was
      held on the 20th of October, 2009, in Honolulu, Hawaii. The theme of this meeting
      was the "Impact of Next Generation Sequencing." Presenters spoke on issues
      ranging from advances in the technology of large-scale genome sequencing to how
      this information can be analyzed to uncover genetic variants associated with
      disease. Many of the challenges resulting from the implementation of these new
      technologies were presented, but possible solutions, or at least paths to the
      solutions, were also given. With the combined efforts of investigators using next
      generation sequencing to help understand the impact of genetic variants on
      disease, the use of the personal genome in medicine will soon become a reality.

PMID- 20127975
TI  - Review and update of mutations causing Waardenburg syndrome.
AB  - Waardenburg syndrome (WS) is characterized by the association of pigmentation
      abnormalities, including depigmented patches of the skin and hair, vivid blue
      eyes or heterochromia irides, and sensorineural hearing loss. However, other
      features such as dystopia canthorum, musculoskeletal abnormalities of the limbs,
      Hirschsprung disease, or neurological defects are found in subsets of patients
      and used for the clinical classification of WS. Six genes are involved in this
      syndrome: PAX3 (encoding the paired box 3 transcription factor), MITF
      (microphthalmia-associated transcription factor), EDN3 (endothelin 3), EDNRB
      (endothelin receptor type B), SOX10 (encoding the Sry bOX10 transcription
      factor), and SNAI2 (snail homolog 2), with different frequencies. In this review
      we provide an update on all WS genes and set up mutation databases, summarize
      molecular and functional data available for each of them, and discuss the
      applications in diagnostics and genetic counseling.

PMID- 20127976
TI  - Biochemical and structural analysis of 14 mutant adsl enzyme complexes and
      correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency.
AB  - Adenylosuccinate lyase (ADSL) deficiency is neurometabolic disease characterized
      by accumulation of dephosphorylated enzyme substrates SAICA-riboside (SAICAr) and
      succinyladenosine (S-Ado) in body fluids of affected individuals. The phenotypic
      severity differs considerably among patients: neonatal fatal, severe childhood,
      and moderate phenotypic forms correlating with different values for the ratio
      between S-Ado and SAICAr concentrations in cerebrospinal fluid have been
      distinguished. To reveal the biochemical and structural basis for this phenotypic
      heterogeneity, we expressed and characterized 19 ADSL mutant proteins identified
      in 16 patients representing clinically distinct subgroups. Respecting compound
      heterozygosity and considering the homotetrameric structure of ADSL, we used
      intersubunit complementation and prepared and characterized genotype-specific
      heteromeric mutant ADSL complexes. We correlated clinical phenotypes with
      biochemical properties of the mutant proteins and predicted structural impacts of
      the mutations. We found that phenotypic severity in ADSL deficiency is correlated
      with residual enzymatic activity and structural stability of the corresponding
      mutant ADSL complexes and does not seem to result from genotype-specific
      disproportional catalytic activities toward one of the enzyme substrates. This
      suggests that the S-Ado/SAICAr ratio is probably not predictive of phenotype
      severity; rather, it may be secondary to the degree of the patient's development
      (i.e., to the age of the patient at the time of sample collection).

PMID- 20127977
TI  - DeltaN133p53 expression levels in relation to haplotypes of the TP53 internal
      promoter region.
AB  - The transcription of the DeltaN133p53 isoform of the TP53 gene is controlled by
      an internal promoter region (IPR) containing eight polymorphisms in 11 common
      haplotypes, following a resequencing of 47 Caucasians. We assayed the functional
      effects of the commonest six haplotypes on the promoter activity with a
      luciferase reporter system, in HeLa and 293T cells. These studies showed that
      different IPR haplotypes are associated with differences in the promoter activity
      resulting in marked variation in the baseline expression of DeltaN133p53. In vivo
      quantitative-polymerase chain reaction (PCR) on human tissues confirmed that the
      baseline levels of DeltaN133p53 showed haplotype specific differences that
      paralleled those seen in vitro. When cell lines were treated with camptothecin,
      the fold-increase in DeltaN133p53 levels was dose-dependent but haplotype
      independent (i.e., similar for all the haplotypes). Finally, we used an
      electrophoretic mobility shift assay to analyze the rs1794287 polymorphism and
      found changes in the pattern of protein binding. This partially confirmed our in
      silico analysis showing that the polymorphism rs1794287 can affect the function
      of the internal promoter by changing its affinity for several transcription
      factors. Thus, we showed that the expression of DeltaN133p53 is under genetic
      control, and suggested the presence of interindividual differences underlying
      this mechanism.

PMID- 20127980
TI  - New foundation focused on the early detection of cancer.

PMID- 20127978
TI  - Genetic diagnosis of familial breast cancer using clonal sequencing.
AB  - Using conventional Sanger sequencing as a reference standard, we compared the
      sensitivity, specificity, and capacity of the Illumina GA II platform for the
      detection of TP53, BRCA1, and BRCA2 mutations in established tumor cell lines and
      DNA from patients with germline mutations. A total of 656 coding variants were
      identified in four cell lines and 65 patient DNAs. All of the known pathogenic
      mutations (including point mutations and insertions/deletions of up to 16
      nucleotides) were identified, using a combination of the Illumina data analysis
      pipeline with custom and commercial sequence alignment software. In our
      configuration, clonal sequencing outperforms current diagnostic methods,
      providing a reduction in analysis times and in reagent costs compared with
      conventional sequencing. These improvements open the possibility of BRCA1/2
      testing for a wider spectrum of at-risk women, and will allow the genetic
      classification of tumors prior to the use of novel PARP inhibitors to treat BRCA
      deficient breast cancers.

PMID- 20127981
TI  - Breast cancer rate continues to decline.

PMID- 20127982
TI  - Disruption of OTC promoter-enhancer interaction in a patient with symptoms of
      ornithine carbamoyltransferase deficiency.
AB  - In a female patient with signs of ornithine carbamoyltransferase deficiency
      (OTCD), the only variation found was a heterozygous single nucleotide
      substitution c.-366A>G. Determination of transcription start sites of human OTC
      95, 119 and 169 bp upstream of the initiation codon located the variation
      upstream of the 5'-untranslated region. We predicted the human promoter and
      enhancer elements from homology with rat and mouse, performed function analysis
      of both regulatory regions and assessed the impact of the promoter variation in
      functional studies using dual luciferase reporter assay. Our data indicate that:
      (i) Full transcriptional activity of human OTC promoter depends on an upstream
      enhancer, as do the rodent promoters. (ii) The promoter variation c.-366A>G does
      not affect the function of the promoter alone but it disrupts the interaction of
      the promoter with the enhancer. (iii) The promoter-enhancer interaction
      contributes to tissue specific expression of OTC in the liver. We conclude that
      mutations in the regulatory regions of OTC can lead to OTCD and should be
      included in genetic testing.

PMID- 20127983
TI  - Hispanics have a unique cancer risk profile.

PMID- 20127984
TI  - Psychometric testing of the Breastfeeding Self-Efficacy Scale-Short Form in a
      sample of Black women in the United States.
AB  - The benefits of breastfeeding increase with duration and exclusivity, but
      significant racial disparities exist in breastfeeding rates. Breastfeeding self
      efficacy, as measured by the Breastfeeding Self-Efficacy Scale Short-Form (BSES
      SF), is a significant predictor of breastfeeding outcomes in diverse samples. The
      purpose of this study was to assess the psychometric properties of the BSES-SF in
      Black women in the US. The psychometric characteristics were consistent with
      previous studies, including internal consistency, comparison with contrasted
      groups, and correlation with the construct of breastfeeding network support.
      Breastfeeding self-efficacy significantly predicted breastfeeding at 4 and 24
      weeks postpartum. The results are consistent with previous research, and they
      suggest the BSES-SF could be used to identify women at risk for prematurely
      discontinuing breastfeeding.

PMID- 20127985
TI  - High-throughput genotyping of mannose-binding lectin variants using high
      resolution DNA-melting analysis.
AB  - High Resolution Melting Analysis (HRMA) is a rapid and sensitive method for
      single nucleotide polymorphism (SNP) analysis. In the present study we present a
      novel HRMA assay to detect three SNPs in close proximity of each other in the
      first exon of the gene encoding mannose-binding lectin (MBL), a key molecule of
      innate immunity. These SNPs have been selected for their known biological and
      clinical relevance. The three SNPs in MBL2 were simultaneously determined in
      sixty-nine human DNA samples using HRMA and a single non-fluorescent melting
      probe, without any post-PCR processing of samples. Combining analyses from
      amplicon melting and probe melting, we have been able to discriminate ten exon 1
      MBL2 genotypes with HRMA, making it a suitable tool for MBL genotyping. A second
      HRMA assay is presented to detect a relevant polymorphism (Y/X SNP) in the MBL2
      promoter region. In conclusion, HRMA is a closed tube assay that is easy to setup
      and lends itself perfectly for high throughput genotyping of MBL2 variants. The
      present study thereby facilitates further clinical studies into the role of MBL
      in inflammatory and infectious disease.

PMID- 20127986
TI  - Evaluation of commercial implants with nanoindentation defines future development
      needs for hydroxyapatite coatings.
AB  - The performance of biomedical implants relies on the ability to assess and refine
      the microstructure of biomaterials. Instrumented nanoindentation was applied to
      determine the mechanical properties of plasma sprayed hydroxyapatite-coated
      implants from different commercial vendors. All biomedical devices contained both
      amorphous and crystalline phases. Nanoindentation of the amorphous phase revealed
      a hardness of 1.5 + or - 0.3 GPa and an elastic modulus of 48 + or - 6 GPa. The
      crystalline phase revealed a range in hardness of 3.0-7.7 GPa. The large range is
      attributed to the presence of porosity, surrounding amorphous areas, and
      hydroxyapatite (unmolten particle cores and recrystallized hydroxyapatite). A
      selection of the powder type (spray-dried or sintered) leads to different
      mechanical properties within the coating. A spray-dried powder provides a lower
      hardness and elastic modulus when unmolten particle cores are included in the
      coating. Meanwhile recrystallized areas are intermediate in hardness. The
      combination of a polished cross-section and nanoindentation offers the ability to
      determine a range of quality control tests including hardness, elastic modulus,
      bond strength, fracture toughness, substrate and coating roughness,
      crystallinity, and coating thickness. Property maps determined from
      nanoindentation will provide a graphical representation of the mechanical
      property distribution within the coating and provide a basis for coating property
      refinements. The assessment of commercial coatings is used a basis for discussion
      of future developments for hydroxyapatite coatings.

PMID- 20127987
TI  - Biodegradable poly(alpha-hydroxy acid) polymer scaffolds for bone tissue
      engineering.
AB  - Synthetic graft materials are emerging as a viable alternative to autogenous bone
      graft and bone allograft for the treatment of critical-sized bone defects. These
      materials can be osteoconductive but are rarely intrinsically osteogenic,
      although this can be greatly enhanced by the application of bone morphogenetic
      proteins (BMPs). This review will discuss the versatility of biodegradable
      poly(alpha-hydroxy acids) for the delivery of BMPs for bone tissue engineering.
      Poly(alpha-hydroxy acids) have a considerable potential for customization and
      adaptability via modification of design parameters, including scaffold
      architecture, composition, and biodegradability. Different fabrication techniques
      will also be discussed.

PMID- 20127988
TI  - Surface modification of titanium and titanium alloys by ion implantation.
AB  - Titanium and titanium alloys are widely used in biomedical devices and
      components, especially as hard tissue replacements as well as in cardiac and
      cardiovascular applications, because of their desirable properties, such as
      relatively low modulus, good fatigue strength, formability, machinability,
      corrosion resistance, and biocompatibility. However, titanium and its alloys
      cannot meet all of the clinical requirements. Therefore, to improve the
      biological, chemical, and mechanical properties, surface modification is often
      performed. In view of this, the current review casts new light on surface
      modification of titanium and titanium alloys by ion beam implantation.

PMID- 20127989
TI  - Stability of poly(3,4-ethylene dioxythiophene) materials intended for implants.
AB  - This study presents experiments designed to study the stability of the conducting
      polymer poly(3,4-ethylene dioxythiophene) (PEDOT), under simulated physiological
      conditions using phosphate-buffered saline (PBS) and hydrogen peroxide (H(2)O(2))
      (0.01 M) at 37 degrees C over a 5- to 6-week period. Voltage pulsing in PBS was
      used as an additional test environment. The influence of switching the counter
      ion used in electropolymerization from polystyrene sulphonate (PSS) to heparin
      was investigated. Absorbance spectroscopy and cyclic voltammetry were used to
      evaluate the material properties. Most of the samples in H(2)O(2) lost both
      electroactivity and optical absorbance within the study period, but PEDOT:PSS was
      found slightly more stable than PEDOT:heparin. Polymers were relatively stable in
      PBS throughout the study period, with around 80% of electroactivity remaining
      after 5 weeks, disregarding delamination, which was a significant problem
      especially for polymer on indium tin oxide substrates. Voltage pulsing in PBS did
      not increase degradation. The counter ion influenced the time course of
      degradation in oxidizing agents.

PMID- 20127990
TI  - Novel biodegradable composite wound dressings with controlled release of
      antibiotics: microstructure, mechanical and physical properties.
AB  - Wound dressings aim to restore the milieu required for skin regeneration and
      protect the wound from environmental threats, including penetration of bacteria.
      The dressings should be easy to apply and remove and maintain a moist healing
      environment. In this study, novel biodegradable composite wound dressings based
      on a polyglyconate mesh and a porous PDLGA binding matrix were developed and
      studied. These novel dressings were prepared by dip-coating woven meshes in
      inverted emulsions, followed by freeze-drying. Their investigation focused on the
      microstructure, mechanical and physical properties, and the release profile of
      the antibiotic drug ceftazidime from the binding matrix. The mechanical
      properties of our wound-dressing structures were found to be superior, combining
      relatively high tensile strength and ductility, which changed only slightly
      during 3 weeks of incubation in an aqueous medium. The parameters of the inverted
      emulsion, the organic-aqueous phase ratio, and the type of surfactant used for
      stabilizing the emulsion were found to affect the microstructure of the binding
      matrix and the resulting properties, i.e., water absorbance, water vapor
      transmission rate, and drug-release profile from the binding matrix. Appropriate
      selection of these parameters can yield composite structures that have the
      desired physical properties and drug release behavior. Thus, these unique
      structures are potentially very useful as burn and ulcer dressings.

PMID- 20127991
TI  - Premixed acidic calcium phosphate cement: characterization of strength and
      microstructure.
AB  - By using a premixed calcium phosphate cement (CPC), the handling properties of
      the cement are drastically improved, which is a challenge for traditional
      injectable CPCs. Previously premixed cements have been based on apatitic cements.
      In this article, acidic cement has been developed and evaluated. Monocalcium
      phosphate monohydrate and beta-tricalcium phosphate were mixed with glycerol to
      form a paste. As the paste does not contain water, no setting reaction starts and
      thus the working time is indefinite. Powder/liquid ratios (P/L) of 2.25, 3.5 and
      4.75 were evaluated. Setting time (ST) and compressive strength (CS) were
      measured after 1 day, 1 week and 4 weeks in phosphate buffered saline (PBS)
      solution, and the corresponding microstructure was evaluated using electron
      microscopy and X-ray diffraction. The ST started when the cements were placed in
      PBS and ranged from 28 to 75 min, higher P/L gave a lower ST. Higher P/L also
      gave a higher CS, which ranged from 2 to 16 MPa. The microstructure mainly
      consisted of monetite, 1-5 microm in grain size. After 4 weeks in PBS, the
      strength increased. As acidic cements are resorbed faster in vivo, this cement
      should allow faster bone regeneration than apatitic cements. Premixed cements
      show a great handling benefit when compared with normal CPCs and can be
      formulated with similar ST and mechanical properties.

PMID- 20127993
TI  - In vitro evaluation of samarium (III) oxide as a bone substituting material.
AB  - The biocompatibility of natural samarium (III) oxide, which has previously been
      used for treatment in bone-related diseases was determined as a first step in its
      evaluation as a bone implant material. Assessment for 28 days using osteoblast
      like cells revealed no indications of cytotoxicity. The cells adhered and
      proliferated on the surface. Furthermore, the differentiation and mineralization
      were observed, indicating a normal biological response of the cells on the
      samarium (III) oxide surface. The in vitro, short term biocompatibility
      assessment of this oxide has indicated its biosafety with no damaging toxic
      effects on the cells and biofunctionality; with an appropriate cell response for
      a bone-contacting material. Hence, samarium (III) oxide deserves recognition in
      the field of biomaterials for its excellent in vitro performance and demonstrates
      that the class of potential bioceramics may be larger than previously thought.
      (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

PMID- 20127992
TI  - Increased expression and cellular localization of spermine oxidase in ulcerative
      colitis and relationship to disease activity.
AB  - BACKGROUND: Polyamines are important in cell growth and wound repair, but have
      also been implicated in inflammation-induced carcinogenesis. Polyamine metabolism
      includes back-conversion of spermine to spermidine by the enzyme spermine oxidase
      (SMO), which produces hydrogen peroxide that causes oxidative stress. In
      ulcerative colitis (UC), levels of spermine are decreased compared to spermidine.
      Therefore, we sought to determine if SMO is involved in UC. METHODS: Colon
      biopsies and clinical information from subjects undergoing colonoscopy for
      evaluation of UC or colorectal cancer screening were utilized from 16 normal
      controls and 53 UC cases. Histopathologic disease severity was graded and the
      Mayo Disease Activity Index (DAI) and endoscopy subscore assessed. SMO mRNA
      expression was measured in frozen biopsies by TaqMan-based real-time polymerase
      chain reaction (PCR). Formalin-fixed tissues were used for SMO
      immunohistochemistry. RESULTS: There was a 3.1-fold upregulation of SMO mRNA
      levels in UC patients compared to controls (P = 0.044), and a 3.7-fold increase
      in involved left colon versus paired uninvolved right colon (P < 0.001). With
      worsening histologic injury in UC there was a progressive increase in SMO
      staining of mononuclear inflammatory cells. There was a similar increase in SMO
      staining with worsening endoscopic disease severity and strong correlation with
      the DAI (r = 0.653, P < 0.001). Inflammatory cell SMO staining was increased in
      involved left colon versus uninvolved right colon. CONCLUSIONS: SMO expression is
      upregulated in UC tissues, deriving from increased levels in mononuclear
      inflammatory cells. Dysregulated polyamine homeostasis may contribute to chronic
      UC by altering immune responses and increasing oxidative stress.

PMID- 20127994
TI  - Inflammatory bowel diseases and health service: the necessity for a new strategy.

PMID- 20127995
TI  - Final adult height of children with inflammatory bowel disease is predicted by
      parental height and patient minimum height Z-score.
AB  - BACKGROUND: This study was designed to elucidate the contribution of parental
      height to the stature of children with inflammatory bowel disease (IBD), who
      often exhibit growth impairment. Accordingly, we compared patients' final adult
      heights and target heights based on measured parental heights and examined
      predictors of final adult height in pediatric IBD patients. METHODS: We
      prospectively analyzed the growth of 295 patients diagnosed between ages 1 and 18
      (211 Crohn's disease [CD], 84 ulcerative colitis [UC]) and their family members
      (283 mothers, 231 fathers, 55 siblings). RESULTS: Twenty-two percent had growth
      impairment (height for age Z-score <-1.64, equivalent to <5th percentile on
      growth curve) in more than 1 measurement since diagnosis; most growth-impaired
      patients had CD (88% CD versus 12% UC). Parents of the growth-impaired group had
      lower mean height Z-scores compared to parents of nongrowth-impaired patients (
      0.67 versus 0.02 for mothers [P < 0.001]; -0.31 versus 0.22 for fathers [P =
      0.002]). For 108 patients who reached adult heights and had available parental
      heights, the growth-impaired group continued to demonstrate lower adult height Z
      scores (-1.38 versus 0.07; P < 0.001). Adult heights were within 1 SD of target
      heights even for the growth-impaired group. Only 11.3% remained persistently
      growth-impaired in adulthood. Multivariate regression analysis demonstrated lower
      parental height and minimum patient height Z-score as significant predictors of
      lower final adult height in IBD. CONCLUSIONS: Parental height is a powerful
      determinant of linear growth even in the presence of chronic inflammation, and
      should be an integral part of the evaluation of growth in IBD children.

PMID- 20127996
TI  - Fabrication and characterization of poly(D,L-lactide-co-glycolide)/hydroxyapatite
      nanocomposite scaffolds for bone tissue regeneration.
AB  - Conventional methods in fabrication of scaffolds based on polymer/bioceramic
      composites frequently make use of solution casting then particle leaching. The
      residues of common organic solvents can get trapped in this technique hence
      provide safety concerns on final scaffold. In this study, N-methyl pyrrolidone
      was used as an approved solvent for parenteral pharmaceutical products especially
      implants with acceptable toxicological profile. A combined freeze drying and
      solvent casting methods were adopted for complete removal of the solvent from
      final scaffold structure. Biodegradable scaffolds based on poly (D,L-lactide-co
      glycolide) and different percentages of nanohydroxyapatite (25, 35, and, 45% w/w)
      were characterized thoroughly regarding porosity, pore distribution as well as
      their bioactivity and biocompatibility. The results showed 70-80% porosity with a
      size distribution in the range of 50-200 mum for different conditions.
      Bioactivity of the scaffolds was directly dependent on the bioceramic content in
      the samples according to the results. Composites and neat samples showed the same
      cytocompatibility profile. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res,
      2010.

PMID- 20127998
TI  - New proteomic approaches for biomarker discovery in inflammatory bowel disease.
AB  - There is an increasing interest in the discovery of new inflammatory bowel
      disease (IBD) biomarkers able to predict the future patterns of disease and to
      help in diagnosis, treatment, and prognosis. A biomarker is a substance that can
      be measured biologically and is associated with an increased risk of the disease.
      Biomarkers can be a genetic testing factor or proteins in biological samples such
      as serum, plasma, and cellular subpopulations. All of them should be studied to
      find out their utility in the management of IBD. Ulcerative colitis and Crohn's
      disease are relapsing and remitting chronic IBDs characterized by a global immune
      defect. The gold standard of their diagnosis is histological evaluation performed
      during endoscopic procedures. Several studies have focused on the identification
      and combination of less invasive diagnostic serum biomarkers. Nowadays,
      diagnostic serum tests are not able either to determine whether and when the
      relapse will occur once the disease is in remission state or to select a patient
      phenotype more responsive to a specific therapy and more susceptible to different
      types of complication. In this review we analyze and report the current
      understanding in IBD biomarkers and discuss potential future biomarkers and new
      developments of proteomics, such as subproteomics, as an innovative approach for
      the classification of patients according to their pattern of protein expression.

PMID- 20127997
TI  - Antibacterial effects of sol-gel-derived bioactive glass nanoparticle on aerobic
      bacteria.
AB  - The aim of this work was to evaluate the antibacterial effect of bioactive glass
      nanopowders. The 58S, 63S, and 72S compositions were prepared via the sol-gel
      technique. Characterization techniques such as X-ray diffraction, transmission
      electron microscopy (TEM), Zetasizer, and X-ray fluorescent were used. The
      antibacterial activity was studied using Escherichia coli, Pseudomonas
      aeruginosa, Salmonella typhi, and Staphylococcus aureus. Cytotoxicity of the
      samples was evaluated using mouse fibroblast L929 cell line. The chemical
      compositions of the prepared samples were as predicted, and the particle size of
      the samples with an amorphous structure mainly ranged over 20-90 nm. At broth
      concentrations below 50 mg/mL, they showed no antibacterial activity. The 58S
      showed the highest antibacterial activity with the minimum bactericidal
      concentrations of 50 and 100 mg/mL for E. coli plus S. aureus and for P.
      aeruginosa, respectively. The 63S exhibited bactericidal and bacteriostatic
      effects on E. coli and S. aureus at concentrations of 100 and 50 mg/mL,
      respectively, at an minimum bactericidal concentrations of 100 mg/mL. However,
      72S bioactive glass nanopowder showed no antibacterial effect. They showed no
      cytotoxicity. It was concluded that bioactive glass nanopowders could be
      considered as good candidates for the treatment of oral bone defects and root
      canal disinfection. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

PMID- 20128000
TI  - Controversy over NOD2, inflammation, and defensins.

PMID- 20127999
TI  - In vitro enzymatic biodegradation of adhesive resin in the hybrid layer.
AB  - Penetration of adhesives into the demineralized dentin surface and their
      subsequent conversion are critically important to longevity of the adhesive resin
      (AR)-dentin bond. The durability of the resin-dentin bond is investigated by
      monitoring the change of adhesive concentration within the hybrid layer (HL) of
      aged specimens using Raman spectroscopy. Absolute molar concentrations of Bis-GMA
      and HEMA were measured across the HL of resin-dentin specimens 24 h after
      photopolymerization and after 24-week storage in one of three media: artificial
      saliva (SAL), SAL containing cholesterol esterase to attack resin (EST), and SAL
      containing bacterial collagenase to attack collagen (COL). No significant
      difference among these groups for both Bis-GMA and HEMA molar concentrations at
      24-h storage was found; however, concentrations decreased from the AR to the
      middle of the HL. Concentrations remained unchanged at any resin-dentin position
      after aging in SAL. In the HL, concentrations significantly decreased with aging
      in COL and tended to decrease in EST. While showing potential enzymatic
      biodegradative effects of endogenous matrix metalloproteinases and salivary
      esterases, this methodology may also prove to be a valuable assessment of new
      chemistries and future approaches to improve resin-dentin bond performance. (c)
      2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

PMID- 20128001
TI  - Growth factor-mediated effects on chondrogenic differentiation of mesenchymal
      stem cells in 3D semi-IPN poly(vinyl alcohol)-poly(caprolactone) scaffolds.
AB  - Cells, signaling molecules and three-dimensional (3D) scaffolds are the major
      contributors to the in vitro regeneration of cartilage. This study evaluates the
      differentiation of mesenchymal stem cells to chondrocytes, in a 3D semi
      interpenetrating polymer network (semi-IPN) scaffold that gives an appropriate
      niche for chondrogenic differentiation. The 3D semi-IPN scaffold poly(vinyl
      alcohol) and poly(caprolactone) mimics the properties of extracellular matrix of
      native cartilage. The chondrogenic differentiation of mesenchymal stem cells on
      the 3D scaffolds is carried out by supplementing signaling molecules like
      TGFbeta1, TGFbeta3, and BMP2 individually and in two different combinations. The
      results indicate that each growth factor supplement or combinations showed a
      different influence on cell morphology, overall distribution of cells, and
      secretion of cartilage specific molecules. We conclude from our results, that a
      combination of TGFbeta3 and BMP2 promotes better differentiation of mesenchymal
      stem cells to chondrocytes in our scaffold. This study hence points out that an
      appropriate combination of 3D scaffolds and signaling molecules are required in
      the differentiation and maintenance of the chondrogenic phenotype during in vitro
      regeneration of cartilage tissue. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater
      Res, 2010.

PMID- 20128002
TI  - Treatment-associated acute myeloid leukemia in a patient with Crohn's disease on
      6-mercaptopurine.

PMID- 20128003
TI  - Response to Baumgart review.

PMID- 20128004
TI  - The effect of a nanothickness coating on rough titanium substrate in the
      osteogenic properties of human bone cells.
AB  - This study evaluated the effect of a bioactive ceramic coating, in the
      nanothickness range, onto a moderately rough surface on the osteogenic behavior
      of human bone cells. The cells were harvested from the mandibular mental region
      and were cultured over Ti-6Al-4V disks of different surfaces: as-machined (M),
      alumina-blasted/acid etched (AB/AE), and alumina-blasted/acid-etched + 300-500 nm
      thickness amorphous Ca- and P-based coating obtained by ion beam-assisted
      deposition (Nano). The culture was then evaluated regarding cell viability,
      adhesion, morphology, immunolocalization of osteopontin (OPN) and alkaline
      phosphatase (ALP). The results showed that the surface treatment did not
      interfere with cell viability. At 1 day, AB/AE and Nano showed higher adhesion
      than the M surface (p < 0.001). Higher adhesion was observed for the M than the
      Nano surface at 7 days (p < 0.005). The percentage of cells showing intracellular
      labeling for OPN at day 1 was significantly higher for the Nano compared to M
      surface (p < 0.03). The percentage of ALP intracellular labeling at 7 days was
      significantly higher for the AB/AE compared to the M surface (p < 0.0065); no
      differences were detected at 14 days. Our results suggest that the presence of a
      thin bioactive ceramic coating on a rough substrate did not favor the events
      related to in vitro osteogenesis. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater
      Res, 2010.

PMID- 20128005
TI  - Lewis and Sumner syndrome following infliximab treatment in Crohn's disease: a
      report of 2 cases.

PMID- 20128006
TI  - Inorganic-organic hybrid scaffolds for osteochondral regeneration.
AB  - Ligament graft failure frequently results from poor integration of the
      replacement tissue with associated bone. Thus, the ability to regenerate the bone
      ligament osteochondral interface would be advantageous in ligament
      reconstruction. At the osteochondral interface, the tissue transitions from a
      bone-like matrix to fibrocartilage. Therefore, a scaffold which promotes a
      spatially regulated transition in cell behavior from osteoblast-like to
      chondrocyte-like would be desirable. Previous research indicates that addition of
      inorganic components to organic scaffolds can enhance the deposition of bone-like
      matrix by associated osteoblasts. We therefore reasoned that a gradient in the
      inorganic content of a hybrid inorganic-organic scaffold may induce an
      osteochondral-like transition in cell phenotype and matrix production. To test
      this hypothesis, hydrogels were prepared from poly(ethylene glycol) (PEG) and
      star poly(dimethylsiloxane) (PDMS(star)). As anticipated, both the matrix
      deposition and phenotype of encapsulated osteoblasts varied with scaffold
      inorganic content, although the directionality of this modulation was contrary to
      expectation. Specifically, osteoblasts appeared to transdifferentiate into
      chondrocyte-like cells with increasing scaffold inorganic content, as indicated
      by increased chondroitin sulfate and collagen type II production and by
      upregulation of sox9, a transcription factor associated with chondrocytic
      differentiation. Furthermore, the deposition of bone-like matrix (collagen type
      I, calcium phosphate, and osteocalcin) decreased with increasing PDMS(star)
      content. The resistance of the PDMS(star)-PEG scaffolds to protein adsorption
      and/or the changes in gel modulus/mesh structure accompanying PDMS(star)
      incorporation may underlie the unexpected increase in chondrocytic phenotype with
      increasing inorganic content. Combined, the present results indicate that
      PDMS(star)-PEG hybrid gels may prove promising for osteochondral regeneration.
      (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

PMID- 20128007
TI  - The combination of micron and nanotopography by H(2)SO(4)/H(2)O(2) treatment and
      its effects on osteoblast-specific gene expression of hMSCs.
AB  - H(2)SO(4)/H(2)O(2) treatment of titanium implants imparts nanofeatures to the
      surface and alters the osteoblast response. The aim of this study was to evaluate
      the effect of H(2)SO(4)/H(2)O(2) treatment of commercially pure Titanium (cpTi)
      surfaces on gene expression of human mesenchymal stem cells (hMSCs)
      differentiated into osteoblasts. Commercially pure grade IV titanium disks (20.0
      mm x 1.0 mm) were polished or polished and subsequently treated by grit blasting
      or grit-blasting/acid etching with an H(2)SO(4)/H(2)O(2) solution. The surfaces
      were divided into three groups: smooth (S), grit-blasted (Gb), and
      nanostructured: grit-blasted/acid etched (Nano). Surfaces were examined by
      scanning electron microscopy and atomic force microscopy. HMSCs were grown on the
      disks. The data points analyzed were at 3, 7, 14, and 28 days. Real-time PCR was
      used to measure the mRNA levels of ALP, BSP, Runx2, OCN, OPN, and OSX. The
      housekeeping gene GAPDH was used as a control. Descriptive statistics were
      calculated using Microsoft Excel. T-test was performed for comparison of mRNA
      levels when compared with S surfaces (p < 0.05). All osteoblast-specific genes
      were regulated in surface-dependent patterns and most of them were upregulated on
      the Nano surfaces. Runx2 and OSX mRNAs were more than threefold upregulated at
      days 14 and 28 on Nano. Higher levels for ALP (38-fold), BSP (76-fold), and OCN
      (3-fold) were also observed on the Nano surfaces. A grit-blasted surface imparted
      with nanofeatures by H(2)SO(4)/H(2)O(2) treatment affected adherent cell bone
      specific gene expression. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res,
      2010.

PMID- 20128008
TI  - Biomechanical implant fixation of CoCrMo coating inferior to titanium coating in
      a canine implant model.
AB  - The use of CoCrMo in orthopedic surgery is not new, and CoCrMo (cobalt-chromium
      molybdenum) is well tolerated. Nevertheless, the alloy is still considered less
      biocompatible than titanium. We therefore wanted to explore the biocompatibility
      of CoCrMo by investigating the biomechanical implant fixation and implant
      osseointegration of CoCrMo (ASTM F-75) porous bead-coated and titanium (ASTM F
      136) porous bead-coated implants. In 10 dogs, the two implant types were inserted
      into the proximal part of the humerus. Implant sites were overdrilled, leaving an
      empty 0.75-mm gap between implant and surrounding bone. The implants were
      observed for 6 weeks and were evaluated by biomechanical push-out test and
      histomorphometry. We found a statistically significant 40% decrease in the
      biomechanical fixation of CoCrMo porous bead-coated implants compared with
      titanium porous bead-coated implants. Implant osseointegration was comparable
      between the two implants; however, a slight decrease in bone volume density
      around CoCrMo implants was observed. Insertions of CoCrMo implants are associated
      with a disturbance of the delicate peri-implant milieu. Even from implants not
      subjected to any mechanical forces, metal ions are liberated and result in intra-
      and extracellular accumulation in the immediate implant vicinity, presenting a
      likely explanation for our findings. A 40% reduction of initial implant fixation
      could prove to be serious because initial implant fixation is critical for long
      term performance. The choice between titanium alloy and CoCrMo should, however,
      ultimately be governed by a comprehensive review of all factors influencing
      clinical implant survival. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res,
      2010.

PMID- 20128009
TI  - A physiologically active polysaccharide hydrogel promotes wound healing.
AB  - When the skin is injured, the subcutaneous tissues and organs are threatened by
      pathogens and excessive water loss. Wound dressings are, therefore, needed to
      protect the wound site from infection and improve the wound closure. Natural
      polysaccharides have been applied for various biomaterials including wound
      dressings, which show their advantages in biocompatibility, low toxicity, and
      pharmaceutical biomedical activity. In this study, a natural polysaccharide
      Bletilla striata polysaccharide (BSP) hydrogel is prepared by an oxidation and
      crosslinking methods. This BSP hydrogel represents preferable swelling ability
      and appropriate water vapor transmission rate. Using a full-thickness trauma
      mouse model, the hydrogel is applied on the in vivo cutaneous wound healing.
      Compared with the control groups, the BSP hydrogel achieves the much better
      healing results. The quantification of the infiltrating inflammatory cells and
      the level of tumor necrosis factor alpha (TNF-alpha) in the BSP group are
      attenuated, whereas the secretion of the epidermal growth factor (EGF) is highly
      elevated. On the 11th day after surgery, the wound area in the BSP hydrogel group
      is only 1/5-1/3 of those in the control groups. This new BSP hydrogel is proved
      to control the inflammatory responses and accelerate the wound closure and has
      potential application in wound healing. (c) 2010 Wiley Periodicals, Inc. J Biomed
      Mater Res, 2010.

PMID- 20128010
TI  - Electrochemical behavior of cobalt-chromium alloys in a simulated physiological
      solution.
AB  - Several cobalt-chromium alloys such as MP35N are used for biomedical implants.
      The electrochemical behavior of these alloys in the passive range differs from
      that of other biomedical alloys. In particular, their cyclic potentiodynamic
      polarization curves exhibit an increase in current at a potential of about 0.4 V
      (SCE). This study examined the electrochemical behavior of MP35N in phosphate
      buffered saline (PBS). Tests were performed on mechanically polished MP35N rod
      and electropolished MP35N wire using cyclic potentiodynamic polarization,
      potentiostatic polarization, and electrochemical impedance spectroscopy. In both
      cases, the surface oxide was shown to undergo two distinct changes as the
      potential is increased. The first change appears to be associated with solid
      state oxidation reactions involving the conversion of Cr(III) to Cr(VI) and of
      Co(II) to Co(III) at similar potentials. The second change involves transpassive
      dissolution that results in the release of chromate and nickel ions. At
      potentials below where these reactions occur, the impedance spectra showed near
      capacitive behavior, and the data could be fitted by a parallel resistance
      capacitance (as a constant phase element) circuit associated with the passive
      oxide film. The thickness of the oxide was determined from the capacitance and
      found to be consistent with surface analytical results reported in the
      literature. Resistivities obtained from resistance values indicated changes in
      the film composition as the potential was increased, particularly after the onset
      of the solid-state reactions. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res
      2010.

PMID- 20128011
TI  - In vivo analysis of gut function and disease changes in a zebrafish larvae model
      of inflammatory bowel disease: a feasibility study.
AB  - BACKGROUND: The aim of this study was to develop a model of inflammatory bowel
      disease (IBD) in zebrafish larvae, together with a method for the rapid
      assessment of gut morphology and function in vivo thereby enabling medium
      throughput compound screening. METHODS: Assays were performed using larval
      zebrafish from 3-8 days postfertilization (d.p.f.) in 96-well plates. Gut
      morphology and peristalsis were observed in vivo using fluorescent imaging
      following ingestion of fluorescent dyes. IBD was induced by addition of 2,4,6
      trinitrobenzenesulfonic acid (TNBS) to the medium within the well. Pathology was
      assessed in vivo using fluorescent imaging and postmortem by histology,
      immunohistochemistry, and electron microscopy. Therapeutic compounds were
      evaluated by coadministration with TNBS. RESULTS: A novel method of investigating
      gut architecture and peristalsis was devised using fluorescent imaging of live
      zebrafish larvae. Archetypal changes in gut architecture consistent with colitis
      were observed throughout the gut. Significant changes in goblet cell number and
      tumor necrosis factor alpha (TNF-alpha) antibody staining were used to quantify
      disease severity and rescue. Prednisolone and 5-amino salicylic acid treatment
      ameliorated the disease changes. Candidate therapeutic compounds (NOS inhibitors,
      thalidomide, and parthenolide) were assessed and a dissociation was observed
      between efficacy assessed using a single biochemical measure (TNF-alpha staining)
      versus an assessment of the entire disease state. CONCLUSIONS: Gut physiology and
      pathology relevant to human disease state can be rapidly modeled in zebrafish
      larvae. The model is suitable for medium-throughput chemical screens and is
      amenable to genetic manipulation, hence offers a powerful novel premammalian
      adjunct to the study of gastrointestinal disease.

PMID- 20128012
TI  - Matrix accumulation by articular chondrocytes during mechanical stimulation is
      influenced by integrin-mediated cell spreading.
AB  - We have shown previously that cyclic compression of newly forming bioengineered
      cartilage in vitro results in improved tissue formation via changes in expression
      of matrix metalloproteases, such as, MT1-MMP (membrane type metalloprotease), and
      increased synthesis of matrix molecules. Several studies have suggested an
      association between MT1-MMP and integrins, which are known to influence cell
      shape. Thus, the objectives of this study were to determine the effect of
      compressive mechanical stimulation on cell shape and the role of integrins and
      MT1-MMP in mediating these changes and influencing matrix accumulation. Bovine
      articular chondrocytes were grown on the surface of a porous ceramic substrate
      for 72 h and then cyclically compressed for 30 min. Scanning electron microscopy
      and morphometric analysis demonstrated that compression induced a rapid,
      transient increase in chondrocyte spreading by 10 min, followed by a retraction
      to prestimulated size within 6 h. This was associated with increased accumulation
      of newly synthesized proteoglycans, as determined by quantification of
      radioisotope incorporation. Blocking the alpha5beta1 integrin, or its beta1
      subunit, inhibited cell spreading and resulted in a partial inhibition of
      compression-induced increase in matrix accumulation. Knockdown of MT1-MMP
      expression partially inhibited cell retraction and resulted in a reduced matrix
      accumulation as well. These results suggest that chondrocyte spreading and
      retraction following cyclic compression in vitro regulates matrix accumulation.
      Understanding the mechanisms that regulate chondrocyte mechanotransduction may
      ultimately lead to the design of improved repair tissue for cartilage damage. (c)
      2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

PMID- 20128013
TI  - Testing the psychometric properties of the Ways of Coping Questionnaire (WCQ) in
      Turkish university students and community samples.
AB  - Ways of Coping Questionnaire (WCQ) has been extensively used to assess coping
      styles in the clinical or non-clinical context. The present study investigates
      the psychometric properties of WCQ in Turkish culture and attempts to get its
      shorter version by using three separate and independent samples (two groups of
      university students and one community sample). The constructive study was
      conducted with a sample of full-time university students (N = 472) and it
      indicated that the most relevant factor structure was seven-factor model. The
      factors were planful problem-solving, seeking refuge in supernatural forces, keep
      to self, seeking social support, seeking refuge in fate, escape/avoidance and
      accepting responsibility. After that, confirmatory factor analysis was performed
      to test the adequacy of these factors with two different samples. Study 1 was
      conducted with a sample of university students (N = 485) and Study 2 was
      conducted with a sample of community (N = 416). Results demonstrated that seven
      factor solution revealed better results in both samples in terms of goodness of
      fit indexes in confirmatory factor analysis. The results of reliability and
      validity analysis revealed that psychometric properties of WCQ were acceptable.
      In addition to getting shorter version of WCQ, the present study enhances cross
      cultural information that increases awareness about the coping styles in a non
      western culture.

PMID- 20128014
TI  - Perspectives on the onset of delusions.
AB  - There are many descriptions in the research literature of the onset of delusions
      in psychosis: it is still not clear however whether there is one specific pathway
      to delusions or in fact several, and the role of social difficulties remains
      controversial. In this research we wished to explore the first person perspective
      of participants who had developed delusions. Interpretative phenomenological
      analysis was used to interview and analyse themes from 28 participants. An
      additional matrix analysis of themes was used to examine the importance of social
      difficulties in relation to types of onset and diagnoses. Our results suggest 3
      types of onset: an eruptive sudden transformation of self or world; a slow
      progressive onset characterised by interconnected changes in meaning and
      experience; and onset beginning in childhood experience. Social difficulties were
      mentioned spontaneously by 17 participants in describing onset and a further 9
      discussed social difficulties when explicitly asked. One feature that appears to
      be present both in the progressive and childhood onset is negative emotion about,
      and preoccupation with, a difficult interpersonal topic over long periods of
      time. The descriptions given suggest that certain ideas or images could take hold
      of a person and become interwoven in his or her thinking and perhaps even begin
      to influence the way the person experienced the world or self. We suggest that it
      may be important for therapeutic work with delusions to articulate a narrative of
      onset.

PMID- 20128015
TI  - Pharmacoepidemiological research using French reimbursement databases: yes we
      can!
AB  - PURPOSE: To describe the reimbursement databases available in France for
      pharmacoepidemiological research and their use. METHODS: France has a publicly
      funded health system that systematically covers the population. Within this
      system, three main insurance schemes provide health services to citizens in
      France and each have their own reimbursement database. Together these three
      databases cover almost 97% of the French population (respectively for 54.5, 3.6,
      and 3.3 million individuals, and a total of 61.4 million individuals). Data in
      these concern patients, prescribers, all the medical acts reimbursed,
      prescription and undertaking of laboratory tests (but without results), private
      hospital data, partial public hospital data and vital status. Their use is
      regulated but access is free and the data are anonymous. PubMed and Scopus were
      searched for relevant studies published from January 1988 to June 2009. RESULTS:
      110 published studies were included. The topics and the study characteristics
      were extremely wide-ranging. The studies assessed patterns of drug use, have
      tested interventions, supported or improved prescribing practices, tested
      compliance with the French governmental Health guidelines, assessed physicians'
      prescribing practices and performed economic and cost-effectiveness assessments.
      The number of articles published increased greatly between 2002 and 2003.
      CONCLUSIONS: The French reimbursement databases were greatly used over the last
      20 years. They can provide data on exposure to drugs and can be used to study
      patterns of drug utilization although their limitations must be considered.

PMID- 20128016
TI  - Impact of Epstein-Barr virus in the clinical evolution of patients with classical
      Hodgkin's lymphoma in Brazil.
AB  - INTRODUCTION: Classical Hodgkin's Lymphoma (cHL) has been frequently associated
      with Epstein-Barr virus (EBV), which can be found in a latent pattern in Reed
      Sternberg (RS) cells. However, the impact of the presence of EBV in RS cells and
      its prognosis are still controversial. We analysed the presence of EBV in RS
      cells and its influence in the clinical evolution of patients with cHL treated in
      two public hospitals in the city of Sao Paulo, Brazil. MATERIALS AND METHODS: We
      selected 97 patients with cHL from 1994 to 2004. Patients were only included in
      this study if they had (1) >18 years, (2) negative HIV serology, (3) undergone
      similar chemotherapy protocols, (4) paraffin blocks available with enough
      material for systematic review and histological reclassification and for
      detection of EBV in RS cells by in situ hybridization and immunohistochemistry
      and (5) clinical, epidemiological and laboratorial parameters available after a
      thorough chart review. RESULTS: EBV was identified in 52.5% of the cases. Mixed
      cellularity (MC) subtype was more common in EBV-related tumours (25.5%)
      (p=0.005). There was no difference on age, gender, stage and the presence of B
      symptoms between the two groups. The presence of EBV did not influence event free
      survival (EFS) (p=0.38) or overall survival (OS) (p=0.80) with a median follow-up
      of 80 months. CONCLUSION: We demonstrate that the prevalence of EBV-related cHL
      in this Brazilian population is 52.5% and, that, the presence of EBV does not
      change the clinical evolution and OS of patients treated with similar
      chemotherapy protocols.

PMID- 20128017
TI  - Genetic and epigenetic changes linked to Chlamydophila psittaci-associated ocular
      adnexal lymphomas.

PMID- 20128018
TI  - Improving the reliability of diagnostic tests in population-based agreement
      studies.
AB  - Many large-scale studies have recently been carried out to assess the reliability
      of diagnostic procedures, such as mammography for the detection of breast cancer.
      The large numbers of raters and subjects involved raise new challenges in how to
      measure agreement in these types of studies. An important motivator of these
      studies is the identification of factors that contribute to the often wide
      discrepancies observed between raters' classifications, such as a rater's
      experience, in order to improve the reliability of the diagnostic process of
      interest. Incorporating covariate information into the agreement model is a key
      component in addressing these questions. Few agreement models are currently
      available that jointly model larger numbers of raters and subjects and
      incorporate covariate information. In this paper, we extend a recently developed
      population-based model and measure of agreement for binary ratings to incorporate
      covariate information using the class of generalized linear mixed models with a
      probit link function. Important information on factors related to the subjects
      and raters can be included as fixed and/or random effects in the model. We
      demonstrate how agreement can be assessed between subgroups of the raters and/or
      subjects, for example, comparing agreement between experienced and less
      experienced raters. Simulation studies are carried out to test the performance of
      the proposed models and measures of agreement. Application to a large-scale
      breast cancer study is presented.

PMID- 20128019
TI  - MicroRNAs, development of Barrett's esophagus, and progression to esophageal
      adenocarcinoma.
AB  - Barrett's esophagus is a premalignant condition caused by gastroesophageal
      reflux. Once developed, it can progress through varying grades of dysplasia to
      esophageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is
      caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis
      and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments
      of RNA that have been shown to control the expression of many human genes. They
      have been implicated in most cellular processes, and the role of miRNAs in
      disease development is becoming increasingly evident. Understanding altered miRNA
      expression is likely to help unravel the molecular mechanisms that underpin the
      development of Barrett's esophagus and its progression to cancer.

PMID- 20128020
TI  - A focus on parietal cells as a renewing cell population.
AB  - The fact that the acid-secreting parietal cells undergo continuous renewal has
      been ignored by many gastroenterologists and cell biologists. In the past, it was
      thought that these cells were static. However, by using (3)H-thymidine
      radioautography in combination with electron microscopy, it was possible to
      demonstrate that parietal cells belong to a continuously renewing epithelial cell
      lineage. In the gastric glands, stem cells anchored in the isthmus region are
      responsible for the production of parietal cells. The stem cells give rise to
      three main progenitors: prepit, preneck and preparietal cells. Parietal cells
      develop either directly from the non-cycling preparietal cells or less commonly
      via differentiation of the cycling prepit and preneck cell progenitors. The
      formation of a parietal cell is a sequential process which involves diminishment
      of glycocalyx, production of cytoplasmic tubulovesicles, an increase in number
      and length of microvilli, an increase in number and size of mitochondria, and
      finally, expansion and invagination of the apical membrane with the formation of
      an intracellular canalicular system. Little is known about the genetic
      counterparts of these morphological events. However, the time dimension of
      parietal cell production and the consequences of its alteration on the biological
      features of the gastric gland are well documented. The production of a new
      parietal cell takes about 2 d. However, mature parietal cells have a long
      lifespan during which they migrate bi-directionally while their functional
      activity for acid secretion gradually diminishes. Following an average lifespan
      of about 54 d, in mice, old parietal cells undergo degeneration and elimination.
      Various approaches for genetic alteration of the development of parietal cells
      have provided evidence in support of their role as governors of the
      stem/progenitor cell proliferation and differentiation programs. Revealing the
      dynamic features and the various roles of parietal cells would help in a better
      understanding of the biological features of the gastric glands and would
      hopefully help in providing a basis for the development of new strategies for
      prevention, early detection and/or therapy of various gastric disorders in which
      parietal cells are involved, such as atrophic gastritis, peptic ulcer disease and
      gastric cancer.

PMID- 20128021
TI  - A systematic review of efficacy and tolerability of mebeverine in irritable bowel
      syndrome.
AB  - We evaluated the efficacy and tolerability of mebeverine, a musculotropic
      antispasmodic agent, in irritable bowel syndrome (IBS) and compared its usual
      dosages by meta-analysis. Medical databases and all relevant literature were
      searched from 1965 to June 2009 for any placebo-controlled clinical trials of
      mebeverine, using search terms such as mebeverine, clinical trials, and IBS.
      Eight randomized trials met our criteria, including six trials that compared
      mebeverine with placebo and two that compared mebeverine tablets with capsules.
      These eight trials included 555 patients randomized to receive either mebeverine
      or placebo with 352 (63%) women and 203 (37%) men in all subtypes of IBS. The
      pooled relative risk (RR) for clinical improvement of mebeverine was 1.13 (95%
      CI: 0.59-2.16, P = 0.7056) and 1.33 (95% CI: 0.92-1.93, P = 0.129) for relief of
      abdominal pain. The efficacy of mebeverine 200 mg compared to mebeverine 135 mg
      indicated RRs of 1.12 (95% CI: 0.96-1.3, P = 0.168) for clinical or global
      improvement and 1.08 (95% CI: 0.87-1.34, P = 0.463) for relief of abdominal pain.
      Thus, mebeverine is mostly well tolerated with no significant adverse effects;
      however, its efficacy in global improvement of IBS is not statistically
      significant.

PMID- 20128022
TI  - Hepatitis D: Scenario in the Asia-Pacific region.
AB  - Hepatitis D virus (HDV) infection is present worldwide and affects all age
      groups. Around 18 million people are estimated to be infected with HDV. An
      important trend in HDV infection is global decline. HDV prevalence has decreased
      significantly in Europe since the 1970s and 1980s when it was first reported. The
      Asia-Pacific region now seems to be where HDV is a major health concern. There is
      a lack of available data from most of the countries from this region; hence, the
      true status of HDV cannot be determined. In South Asia, most of the countries
      have conditions that are favorable for the spread of hepatitis B and other
      related infections. Countries like Pakistan and Iran have shown an increase in
      HDV prevalence over a period of time. Other countries and region like China,
      Turkey, Australia, Japan, India and Taiwan, some of which had very high HDV
      prevalence in the past, have shown a decline in the incidence, but high
      prevalence persists in some. Intravenous drug abusers, homosexual men and women,
      prostitutes, and people on hemodialysis are the groups with very high HDV
      prevalence.

PMID- 20128023
TI  - Effects of perinatal protein deprivation and recovery on esophageal myenteric
      plexus.
AB  - AIM: To evaluate effects of pre- and postnatal protein deprivation and postnatal
      recovery on the myenteric plexus of the rat esophagus. METHODS: Three groups of
      young Wistar rats (aged 42 d) were studied: normal-fed (N42), protein-deprived
      (D42), and protein-recovered (R42). The myenteric neurons of their esophagi were
      evaluated by histochemical reactions for nicotinamide adenine dinucleotide
      (NADH), nitrergic neurons (NADPH)-diaphorase and acetylcholinesterase (AChE),
      immunohistochemical reaction for vasoactive intestinal polypeptide (VIP), and
      ultrastructural analysis by transmission electron microscopy. RESULTS: The
      cytoplasms of large and medium neurons from the N42 and R42 groups were intensely
      reactive for NADH. Only a few large neurons from the D42 group exhibited this
      aspect. NADPH detected in the D42 group exhibited low reactivity. The AChE
      reactivity was diffuse in neurons from the D42 and R42 groups. The density of
      large and small varicosities detected by immunohistochemical staining of VIP was
      low in ganglia from the D42 group. In many neurons from the D42 group, the double
      membrane of the nuclear envelope and the perinuclear cisterna were not
      detectable. NADH and NADPH histochemistry revealed no group differences in the
      profile of nerve cell perikarya (ranging from 200 to 400 microm(2)). CONCLUSION:
      Protein deprivation causes a delay in neuronal maturation but postnatal recovery
      can almost completely restore the normal morphology of myenteric neurons.

PMID- 20128024
TI  - Significance and relationship between Cripto-1 and p-STAT3 expression in gastric
      cancer and precancerous lesions.
AB  - AIM: To explore the relationship between Cripto-1 (CR-1) and tyrosine
      phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric
      carcinogensis and metastasis. METHODS: The PV9000 immunohistochemical method was
      used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched
      normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal
      metaplasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p
      STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3%
      and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric
      mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p
      STAT3 (78.3% and 66.7%) were significantly higher in GC with lymph node
      metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1
      expression was also related to histological and Lauren's types of GC (P < 0.001).
      Furthermore, there was positive relationship between CR-1 and p-STAT3 expressions
      in GC (r(k) = 0.189, P = 0.002). CONCLUSION: The up-regulation of CR-1 and p
      STAT3 may play important roles in gastric carcinogenesis and lymph node
      metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the
      relevant molecular mechanism requires further investigations.

PMID- 20128025
TI  - Understanding of chemoprophylaxis and concordance in inflammatory bowel disease.
AB  - AIM: To assess patients' understanding for the reasons for taking 5
      aminosalicylic acid or ursodeoxycholic acid as chemoprophylaxis against
      colorectal carcinoma associated with inflammatory bowel disease (IBD). METHODS: A
      questionnaire-based study using a 5-point opinion scale was performed. One
      hundred and ninety-two patients with colitis only and 74 patients with primary
      sclerosing cholangitis and IBD were invited to take part. RESULTS: Overall
      response rate was 58%. Sixty-four percent of patients claimed full concordance
      with chemoprophylaxis for maintenance of remission. Eighty-four percent of
      patients considered daily concordance during remission to be very important.
      Seventy-five percent stated they understood the reasons for taking the drugs.
      However, only 50% of the patients were aware of any link of their condition to
      bowel cancer. Seventy-nine percent of patients felt their concordance and
      understanding would be improved if they were informed of the chemoprophylactic
      potential of the medication. CONCLUSION: Despite good self-reported concordance,
      half of the patients were unaware of an association between colitis and bowel
      cancer. Explaining the potential chemoprophylactic benefits may enhance patients'
      overall concordance to 5-aminosalicylic acid and ursodeoxycholic acid and help
      maintain remission.

PMID- 20128026
TI  - Crypt abscess-associated microbiota in inflammatory bowel disease and acute self
      limited colitis.
AB  - AIM: To evaluate whether crypt abscesses from inflammatory bowel disease (IBD)
      patients contain bacteria and to establish their nature. METHODS: We studied 17
      ulcerative colitis patients, 11 Crohn's disease patients, 7 patients with acute
      self-limited colitis (ASLC) and normal colonic biopsies from 5 subjects who
      underwent colonoscopy for colon cancer screening. A fluorescent in situ
      hybridization technique was applied to colonic biopsies to assess the microbiota
      composition of the crypts and crypt abscesses. RESULTS: Crypts colonized by
      bacteria were observed in 42.9% and 3.6% of ASLC and IBD patients, respectively
      (P = 0.019). Crypt abscesses colonized by bacteria were observed in 28.6% and
      0.0% of ASLC and IBD patients, respectively (P = 0.035). CONCLUSION: These
      results do not support the hypothesis that crypt abscesses in IBD are the result
      of localized dysbiosis arising from persistence of living bacteria colonizing the
      crypts.

PMID- 20128027
TI  - Large endoscopic mucosal resection for colorectal tumors exceeding 4 cm.
AB  - AIM: To evaluate the feasibility and the outcome of endoscopic mucosal resection
      (EMR) for large colorectal tumors exceeding 4 cm (LCRT) undergoing piecemeal
      resection. METHODS: From January 2005 to April 2008, 146 digestive tumors larger
      than 2 cm were removed with the EMR technique in our department. Of these, 34
      tumors were larger than 4 cm and piecemeal resection was carried out on 26
      colorectal tumors. The mean age of the patients was 71 years. The mean follow-up
      duration was 12 mo. RESULTS: LCRTs were located in the rectum, left colon,
      transverse colon and right colon in 58%, 15%, 4% and 23% of cases, respectively.
      All were sessile tumors larger than 4 cm with a mean size of 4.9 cm (4-10 cm).
      According to the Paris classification, 34% of the tumors were type Is, 58% type
      IIa, 4% type IIb and 4% type IIc. Pathological examination showed tubulous
      adenoma in 31%, tubulo-villous adenoma in 27%, villous adenoma in 42%, high-grade
      dysplasia in 38%, in situ carcinoma in 19% of the cases and mucosal carcinoma
      (m2) in 8% of the cases. The two cases (7.7%) of procedural bleeding that
      occurred were managed endoscopically and one small perforation was treated with
      clips. During follow-up, recurrence of the tumor occurred in three patients
      (12%), three of whom received endoscopic treatment. CONCLUSION: EMR for tumors
      larger than 4 cm is a safe and effective procedure that could compete with
      endoscopic submucosal dissection, despite providing incomplete histological
      assessment.

PMID- 20128028
TI  - Phlebotomy improves histology in chronic hepatitis C males with mild iron
      overload.
AB  - AIM: To investigate the usefulness of mild iron depletion and the factors
      predictive for histological improvement following phlebotomy in Caucasians with
      chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with
      persistently elevated serum aminotransferase levels and non responders to, or
      unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin <
      or = 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by
      at least one point reduction in the staging score or, in case of unchanged stage,
      as at least two points reduction in the grading score (Knodell), was evaluated in
      two subsequent liver biopsies (before and at the end of phlebotomy, 48 +/- 16 mo
      apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological
      improvement occurred in 12/28 phlebotomized patients. Only males responded to
      phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high
      histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P =
      0.04) before treatment were associated with histological improvement.
      Multivariate logistic analysis showed that in males high HIC was the only
      predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI:
      1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC > or =
      20 micromol/g showed histological improvements at the second biopsy. CONCLUSION:
      Male CHC Caucasian non-responders to antiviral therapy with low-grade iron
      overload can benefit from mild iron depletion by long-term phlebotomy.

PMID- 20128029
TI  - Metabolic investigations in patients with hepatitis B and C.
AB  - AIM: To investigate the similarities and dissimilarities in patients with
      hepatitis B and hepatitis C, clinically and metabolically. METHODS: Fifty
      patients with hepatitis B virus and hepatitis C virus infection were included in
      this study, along with fifty healthy controls for comparison purposes.
      Intravenous blood (10 mL) samples from patients and healthy subjects were
      collected and made to clot before serum was separated and immediately levels of
      the enzymes, alkaline phosphatase (ALK), creatinine phosphokinase (CPK), lactate
      dehydrogenase (LDH), serum glutamate oxaloacetate transaminase (s-GOT) and serum
      glutamate pyruvate transaminase (s-GPT) were determined by a kit method. For
      total content of each metal the serum samples were analyzed using atomic
      absorption spectrophotometry. Levels of cholesterol, triglycerides, urea,
      creatinine and uric acid were determined using a kit method on Microlab 300.
      RESULTS: Serum magnesium and copper levels remained unchanged, whereas the
      concentration of zinc decreased and iron increased significantly in both groups
      of patients. Total antioxidant activity was significantly decreased in both
      hepatitis B and C. Among the enzymes analyzed, ALK, s-GPT, LDH and s-GOT were all
      significantly increased in both patients with hepatitis B and C whereas CPK was
      significantly decreased in patients with hepatitis B and remained unchanged in
      patients with hepatitis C. CONCLUSION: The information accumulated by this study
      will help provide a better understanding of involved metabolic processes in order
      to design appropriate therapeutic approaches for treating these patients, so they
      can recover and lead normal lives.

PMID- 20128030
TI  - Hemodynamics in the immediate post-transplantation period in alcoholic and viral
      cirrhosis.
AB  - AIM: To study the hemodynamics in the immediate post transplant period and
      compare patients with alcoholic vs viral cirrhosis. METHODS: Between 2000-2003,
      38 patients were transplanted for alcoholic cirrhosis and 28 for postviral
      cirrhosis. Heart rate (HR), central venous pressure (CVP), mean arterial pressure
      (MAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), systemic
      vascular resistance index (SVRI), pulmonary artery pressure (PAP), and pulmonary
      vascular resistance index (PVRI) were measured immediately and 24 h post
      transplantation. RESULTS: Hyperdynamic circulation persisted at 24 h following
      transplantation with an elevated CI of 5.4 +/- 1.3 L/(min x m(2)) and 4.9 +/- 1.0
      L/(min x m(2)) in the viral and alcoholic groups, respectively, and was
      associated with a decreased SVRI. Within the first 24 h, there was a significant
      decrease in HR and increase in MAP; the extent of the change was similar in both
      groups. The CVP, PCWP, and SVRI increased, and CI decreased in the viral
      patients, but not the alcoholic patients. Alcoholics showed a lower PVRI (119 +/-
      52 dynes/(cm(5) x m(2)) vs 166 +/- 110 dynes/(cm(5) x m(2)), P < 0.05) and PAP
      (20 +/- 7 mmHg vs 24 +/- 7 mmHg, P < 0.05) compared to the viral group at 24 h.
      CONCLUSION: Hyperdynamic circulation persists in the immediate post-transplant
      period with a faster improvement in the viral group. Alcoholic patients have a
      more pronounced pulmonary vasodilatation.

PMID- 20128031
TI  - Effect of domperidone therapy on nocturnal dyspeptic symptoms of functional
      dyspepsia patients.
AB  - AIM: To investigate the incidence of nocturnal dyspeptic symptoms in patients
      with functional dyspepsia (FD) and whether prokinetic drugs can alleviate them.
      METHODS: Eighty-five consecutive Chinese patients with FD were included in this
      study. One week after single-blinded placebo run-in treatment, baseline nocturnal
      intragastric pH, bile reflux and nocturnal dyspeptic symptoms of eligible
      patients, including epigastric pain or discomfort, abdominal distention and
      belching, were investigated with questionnaires. Patients exhibiting nocturnal
      dyspeptic symptoms were randomly and double-blindly assigned to domperidone group
      or placebo group. Nocturnal intragastric pH and percentage of duodenogastric bile
      reflux time were determined after treatment. RESULTS: Of the 85 FD patients, 2
      females without nocturnal symptoms, who responded to placebo run-in treatment,
      were excluded from the study, 30 (36.1%) exhibited nocturnal dyspeptic symptoms
      with increased duodenogastric bile reflux time (intragastric bilirubin absorbance
      > 0.14) and mean gastric pH (confirming the existence of bile reflux) (P = 0.021,
      0.023) at night were included in the study. Of these 30 patients, 21 (70%) had
      overt nocturnal duodenogastric bile reflux, which was significantly higher than
      that of those without nocturnal symptoms (P = 0.026). The 30 patients were
      allocated to domperidone group or placebo group (n = 15). The nocturnal
      duodenogastric bile reflux and gastric pH were significantly decreased after
      domperidone treatment (P = 0.015, 0.021). The severity score of nocturnal
      dyspeptic symptoms was also significantly decreased after domperidone treatment
      (P = 0.010, 0.015, 0.026), which was positively correlated with the reduced
      nocturnal bile reflux or gastric pH (r = 0.736, 0.784, 0.753 or r = 0.679, 0.715,
      0.697, P = 0.039, 0.036, 0.037 or P = 0.043, 0.039, 0.040). CONCLUSION: A
      subgroup of Chinese FD patients show overt nocturnal dyspeptic symptoms, which
      may be correlated with the excessive nocturnal duodenogastric bile reflux.
      Domperidone therapy can alleviate these symptoms.

PMID- 20128032
TI  - Natural course of chronic hepatitis B is characterized by changing patterns of
      programmed death type-1 of CD8-positive T cells.
AB  - AIM: To investigate if and how programmed death type-1 (PD-1) expression affects
      the natural course of hepatitis B virus (HBV) infection. METHODS: Sixty-four
      patients in different natural stages of chronic HBV infection were enrolled in
      this study. PD-1 expression in total T cells was detected by flow cytometry.
      Levels of total CD8+ T cell responses and proliferation in relation to PD-1
      expression levels were analyzed with intracellular staining and PD-1/PD-L1
      blockage. RESULTS: The PD-1 expression in T cells was dynamically changed during
      the natural course of chronic HBV infection, did not significantly increase in
      the immune tolerance phase, and returned to normal in the inactive virus carrier
      stage. Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in
      the immune tolerance and inactive virus carrier stages of chronic HBV infection.
      However, it could significantly restore the T-cell response in the immune
      clearance stage of chronic HBV infection. Furthermore, the PD-1 expression level
      in T cells was associated with the alanine aminotransferase level during the
      immune clearance stage of chronic HBV infection. CONCLUSION: The PD-l/PD-L1
      pathway plays a different role in T-cell response during the natural course of
      chronic HBV infection.

PMID- 20128033
TI  - Serum thymosin beta4 levels in patients with hepatitis B virus-related liver
      failure.
AB  - AIM: To investigate whether serum thymosin beta4 can provide diagnostic or
      prognostic information in liver failure patients caused by chronic hepatitis B
      virus (HBV) infection. METHODS: Serum thymosin beta4 levels were measured in 30
      patients with acute-on-chronic liver failure (ACLF), 31 patients with chronic
      liver failure (CLF), 30 patients with compensated liver cirrhosis (CR) and 32
      patients with chronic hepatitis B and 30 healthy controls. Serum thymosin beta4
      levels were measured by enzyme-linked immunosorbent assay and Child-Pugh and
      model for end-stage liver disease (MELD) scores were calculated for each patient
      on admission. RESULTS: Compared with healthy controls, serum thymosin beta4
      levels in ACLF, CLF, CR and chronic hepatitis B patients were significantly
      lower, 6.5047 (4.7879-10.5314) microg/mL vs 0.4632 (0.2759-0.8768) microg/mL,
      0.6981 (0.5209-1.2008) microg/mL, 1.8053 (0.8110-2.3397) microg/mL, 3.7803
      (1.8570-6.4722) microg/mL, respectively (P < 0.001). The levels of thymosin beta4
      in liver failure (ACLF or CLF) patients were markedly lower than that in CR (P <
      0.001), and a difference was also found between CLF and ACLF patients (P =
      0.038). In patients with chronic liver disease, there was a positive relationship
      between thymosin beta4 levels and albumin, choline esterase, and platelet (P <
      0.001), and negative relationship with alanine aminotransferase (P = 0.020),
      aspartate aminotransferase, total bilirubin, international normalized ratio of
      prothrombin time, and Child-Pugh and MELD scores (P < 0.001). Of the 61 liver
      failure patients, the thymosin beta4 levels of non-survivors were significantly
      lower than that of survivors (P = 0.007). Receiver operating characteristics
      analysis identified a thymosin beta4 cutoff level of 0.5708 microg/mL for
      predicting poor prognosis in all liver failure patients. The serial thymosin
      beta4 values were observed in 13 liver failure inpatients. Lower initial values
      were observed in the death. While greater improvement in thymosin beta4 value was
      found in those who recovered from the disease. CONCLUSION: Serum thymosin beta4
      can be used as an important potential predictor for liver failure caused by
      chronic HBV infection.

PMID- 20128034
TI  - Clinical and endoscopic analysis of gastric Dieulafoy's lesion.
AB  - AIM: To investigate the incidence, location, clinical presentation, diagnosis and
      effectiveness of endoscopic treatment of gastric Dieulafoy's lesion (DL) in
      China. METHODS: All patients who received emergency upper gastrointestinal (GI)
      endoscopy due to gastric DL from February 2000 to August 2008 at GI endoscopy
      center of Renmin Hospital of Wuhan University were included in this study. The
      clinical presentation, medical history, location and characteristics of DL
      methods and effectiveness of therapy of patients with DL were retrospectively
      analysed by chart reviews. Long-term follow-up data were collected at outpatient
      clinics or telephone interviews. RESULTS: Fifteen patients were diagnosized with
      DL, which account for 1.04% of the source of bleeding in acute non-variceal upper
      GI bleeding. Common comorbidities were found in one patient with hypertension and
      diabetic mellitus. Hemoclip or combined therapy with hemoclip produced primary
      hemostasis in 92.8% (13/14) of patients. CONCLUSION: DL is uncommon but life
      threatening in China. Hemoclip proved to be safe and effective in controlling
      bleeding from DL.

PMID- 20128035
TI  - Inhibition of allogeneic T-cell response by Kupffer cells expressing indoleamine
      2,3-dioxygenase.
AB  - AIM: To explore the possibility and mechanism of inhibiting allogeneic T-cell
      responses by Kupffer cells (KC) pretreated with interferon-gamma (IFN-gamma) in
      vitro. METHODS: The expressions of indoleamine 2,3-dioxygenase (IDO) mRNA and
      FasL mRNA in KC pretreated with IFN-gamma were studied with real-time polymerase
      chain reaction (PCR). The catabolism of tryptophan by IDO from KC was analyzed by
      high performance liquid chromatography. Allogeneic T-cell response was used to
      confirm the inhibition of KC in vitro. The proliferation of lymphocytes was
      detected using [(3)H] thymidine incorporation. Cell cycle and lymphocyte
      apoptosis were evaluated by flow cytometric assay. RESULTS: Real-time PCR
      revealed IDO mRNA and FasL mRNA expressions in KC pretreated with IFN-gamma, and
      IDO catabolic effect was confirmed by a decrease in tryptophan and increase in
      kynurenine concentration. KC expressing IDO and FasL in BABL/c mice acquired the
      ability to suppress the proliferation of T-cells from C57BL/6, which could be
      blocked by addition of 1-methyl-tryptophan and anti-FasL antibody. KC expressing
      IDO could induce allogeneic T-cell apoptosis. CONCLUSION: In addition to Fas/FasL
      pathway, IDO may be another mechanism for KC to induce immune tolerance.

PMID- 20128036
TI  - DNA polymorphism and risk of esophageal squamous cell carcinoma in a population
      of North Xinjiang, China.
AB  - AIM: To investigate the role of metabolic enzyme and DNA repair genes in
      susceptibility of esophageal squamous cell carcinoma (ESCC). METHODS: A case
      control study was designed with 454 samples from 128 ESCC patients and 326
      gender, age and ethnicity-matched control subjects. Genotypes of 69 single
      nucleotide polymorphisms (SNPs) of metabolic enzyme (aldehyde dehydrogenase-2,
      ALDH2; alcohol dehydrogenase-1 B, ADHB1; Cytochrome P450 2A6, CYP2A6) and DNA
      repair capacity genes (excision repair cross complementing group 1, ERCC1; O(6)
      methylguanine DNA methyltransferase, MGMT; xeroderma pigmentosum group A, XPA;
      xeroderma pigmentosum group A, XPD) were determined by the Sequenom MassARRAY
      system, and results were analyzed using unconditional logistic regression
      adjusted for age, gender. RESULTS: There was no association between the variation
      in the ERCC1, XPA, ADHB1 genes and ESCC risk. Increased risk of ESCC was
      suggested in ALDH2 for frequency of presence C allele of SNP [Rs886205: 1.626
      (1.158-2.284)], XPD for C allele [Rs50872: 1.482 (1.058-2.074)], and MGMT for A
      allele [Rs11016897: 1.666 (1.245-2.228)]. Five variants of MGMT were associated
      with a protective effect on ESCC carcinogenesis, including C allele [Rs7069143:
      0.698 (0.518-0.939)], C allele [Rs3793909: 0.653 (0.429-0.995)], A allele
      [Rs12771882: 0.719 (0.524-0.986)], C allele [Rs551491: 0.707 (0.529-0.945)], and
      A allele [Rs7071825: 0.618 (0.506-0.910)]. At the genotype level, increased risk
      of ESCC carcinogenesis was found in homozygous carriers of the ALDH2 Rs886205 [CC
      vs TT, odds ratios (OR): 3.116, 95% CI: 1.179-8.234], MGMT Rs11016879 (AA vs GG,
      OR: 3.112, 95% CI: 1.565-6.181), Rs12771882 (AA vs GG, OR: 2.442, 95% CI: 1.204
      4.595), and heterozygotes carriers of the ALDH2 Rs886205 (CT vs TT, OR: 3.930,
      95% CI: 1.470-10.504), MGMT Rs11016879 (AG vs GG, OR: 3.933, 95% CI: 2.216-6.982)
      and Rs7075748 (CT vs CC, OR: 1.949, 95% CI: 1.134-3.350), respectively. Three
      variants were associated with a protective effect on ESCC carcinogenesis,
      carriers of the MGMT Rs11016878 (AG vs AA, OR: 0.388, 95% CI: 0.180-0.836),
      Rs7069143(CT vs CC, OR: 0.478, 95% CI: 0.303-0.754) and Rs7071825 (GG vs AA, OR:
      0.493, 95% CI: 0.266-0.915). Increased risk of ESCC metastasis was indicated in
      MGMT for frequency of presence C allele [Rs7068306: 2.204 (1.244-3.906)], A
      allele [Rs10734088: 1.968 (1.111-3.484)] and C allele [Rs4751115: 2.178 (1.251
      3.791)]. Two variants in frequency of presence C allele of CYP2A6 [Rs8192720:
      0.290 (0.099-0.855)] and A allele of MGMT [Rs2053139: 0.511 (0.289-0.903)] were
      associated with a protective effect on ESCC progression. Increased risk of ESCC
      metastasis was found in heterozygote carriers of the MGMT Rs7068306 (CG vs CC,
      OR: 4.706, 95% CI: 1.872-11.833). CONCLUSION: Polymorphic variation in ALDH2, XPD
      and MGMT genes may be of importance for ESCC susceptibility. Polymorphic
      variation in CYP2A6 and MGMT are associated with ESCC metastasis.

PMID- 20128037
TI  - Rectal perforation from endometriosis in pregnancy: case report and literature
      review.
AB  - This case report describes a woman with spontaneous rectal perforation from
      decidualized endometriosis in pregnancy. A 37-year-old woman was admitted to our
      hospital at 30 wk of pregnancy with symptoms suggestive of pyelonephritis, which
      persisted until 33 wk of gestation when delivery of a premature male baby was
      performed through a cesarean section. On postoperative day 2, an abdominal
      computed tomography showed free air in the peritoneal cavity and a pelvic
      abscess. Explorative celiotomy revealed a diffuse severe fecaloid peritonitis
      that originated from a 3-cm wide rectal perforation. A Hartmann operation was
      then performed. Histopathological findings were consistent with decidualization
      of the rectal wall. Only 20 cases of intestinal perforation due to endometriosis
      have been reported in the literature. This report is believed to be the first
      case of spontaneous rectal perforation from endometriosis in pregnancy, and it
      shows the potential occurrence of serious and unexpected complications of the
      disease.

PMID- 20128038
TI  - Primary mixed germ cell tumor of the liver with sarcomatous components.
AB  - Germ cell tumor (GCT) of the liver is extremely rare. Here, we describe a case of
      hepatic mixed GCT with significant sarcomatous components and elevated serum
      alpha-fetoprotein (AFP) in a 34-year-old man. Histopathologically, the tumor was
      composed of two GCTs components: yolk sac tumor and immature teratoma. The
      predominant components of immature teratoma consisted of several types of tissue
      that represented different germinal layers (endoderm, mesoderm and ectoderm) and
      showed varying degrees of differentiation with significant sarcomatous
      components. The yolk sac component showed positivity for AFP and cytokeratin
      (AE1/AE3). The immature teratoma components showed positivity for varying
      differentiation markers. Interphase cytogenetic analysis revealed that the yolk
      sac tumor and immature teratoma were positive for i(12p) and 12p over
      representation. In particular, the rhabdomyoblastic components also showed
      typical i(12p) and 12p overrepresentation. This suggested that sarcomatous
      components may be associated with dedifferentiation or malignant transformation
      of certain mesenchymal components within teratoma.

PMID- 20128039
TI  - No evidence of Permacol rejection presented by Wotton and Akoh.
AB  - Wotton and Akoh in their previously reported case in this journal postulate that
      Permacol rejected. This letter provides a detailed critique of that claim and
      provides an alternative explanation for the histological data provided by the
      authors. It is also argued that Wotton and Akoh have misrepresented one of the
      papers in the discussion in their article and a clarification of that referenced
      paper is given.

PMID- 20128040
TI  - Effect of acupressure and trigger points in treating headache: a randomized
      controlled trial.
AB  - The efficacy of acupressure in relieving pain has been documented; however, its
      effectiveness for chronic headache compared to the muscle relaxant medication has
      not yet been elucidated. To address this, a randomized, controlled clinical trial
      was conducted in a medical center in Southern Taiwan in 2003. Twenty-eight
      patients suffering chronic headache were randomly assigned to the acupressure
      group (n = 14) or the muscle relaxant medication group (n = 14). Outcome measures
      regarding self-appraised pain scores (measured on a visual analogue scale; VAS)
      and ratings of how headaches affected life quality were recorded at baseline, 1
      month after treatment, and at a 6-month follow-up. Pain areas were recorded in
      order to establish trigger points. Results showed that mean scores on the VAS at
      post-treatment assessment were significantly lower in the acupressure group
      (32.9+/-26.0) than in the muscle relaxant medication group (55.7+/-28.7) (p =
      0.047). The superiority of acupressure over muscle relaxant medication remained
      at 6-month follow-up assessments (p = 0.002). The quality of life ratings related
      to headache showed similar differences between the two groups in the post
      treatment and at six-month assessments. Trigger points BL2, GV20, GB20, TH21, and
      GB5 were used most commonly for etiological assessment. In conclusion, our study
      suggests that 1 month of acupressure treatment is more effective in reducing
      chronic headache than 1 month of muscle relaxant treatment, and that the effect
      remains 6 months after treatment. Trigger points help demonstrate the treatment
      technique recommended if a larger-scale study is conducted in the future.

PMID- 20128041
TI  - A randomized controlled pilot trial of "Feiji Recipe" on quality of life of non
      small cell lung cancer patients.
AB  - In order to pilot a study observing the feasibility of applying the Core Quality
      of Life Questionnaire (QLQ-C30) version 2.0 to assess the quality of life (QOL)
      of patients with NSCLC treated with Feiji Recipe, a randomized, parallel
      controlled clinical trial was conducted in the university-affiliated hospital.
      Seventy inpatients who met the inclusion criteria were randomized into the study,
      and 60 cases were available as subjects for QOL data analysis. The subjects were
      randomly assigned to one of three groups: the Feiji Recipe group (A); the Feiji
      Recipe combined with chemotherapy group (B); and the chemotherapy group (C) in
      which the patients were treated with vinorelbine plus cisplatin (NP) or
      gemcitabine plus cisplatin (GP). QOL was assessed with the Chinese version of the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire C30. Sixty cases that finished the questionnaires were analyzed,
      and we found that patients who received chemotherapy had low QOL, in terms of
      their global health, role, emotional, social, economic status and symptom burden
      including fatigue, nausea and vomiting, dyspnea, loss of appetite and abnormal
      bowel movements. Simultaneous treatment with Feiji Recipe and chemotherapy was
      able to prevent the worsening of function in terms of role, social, fatigue and
      global health. The Core Quality of Life Questionnaire (QLQ-C30) version 2.0 can
      be used to evaluate the QOL of patients with NSCLC treated by Chinese herbal
      medicine. Feiji Recipe might partially improve the QOL of NSCLC patients when
      administered alone or in combination with chemotherapy. No unexpected side
      effects were observed. However, further double-blinded placebo controlled studies
      are strongly recommended.

PMID- 20128042
TI  - Differences in individual efficacy of two Sairei-to preparations (Sojyutu-Sairei
      to and Byakujyutu-Sairei-to) on recurrent spontaneous abortions of autoimmune
      etiologies evaluated by antinuclear antibody and anticardiolipin antibody titers.
AB  - The differences in individual efficacy of two Sairei-to preparations (Sojyutu
      Sairei-to and Byakujyutu-Sairei-to) on antinuclear antibody (ANA) and
      anticardiolipin antibody (ACLA) positive recurrent spontaneous abortion (RSA) was
      analyzed in 52 patients (a total of 61 treatment sessions). Patients who failed
      to respond to initial treatment with Sojyutu-Sairei-to were additionally treated
      with Byakujyutu- Sairei-to, and the time course of ANA and ACLA titers in these
      patients was analyzed. ACLA titers were decreased significantly by the treatment
      of Byakujyutu-Sairei-to, however, the percentage of successfully prevented
      abortion cases did not differ significantly between the Sojyutu-Sairei-to
      treatment group and the Byakujyutu-Sairei-to treatment group. ACLA titer was
      decreased in all 10 cases where abortion was successfully prevented by the
      treatment with Sojyutu-Sairei-to or Byakujyutu-Sairei-to. In the cases where both
      ANA and ACLA were decreased following treatment with Sojyutu-Sairei-to or
      Byakujyutu-Sairei-to, the percentage of cases rated as "Kyo" and "Rikan" were
      significantly higher in the Byakujyutu-Sairei-to group. These results indicate
      that Byakujyutu-Sairei-to is effective against ACLA positive RSA through the
      antibody-reducing activity, which differs from that of Sojyutu-Sairei-to in
      individual cases. On the basis of these results, Sairei-to therapy, which is
      superior to aspirin and heparin in terms of efficacy and safety, is recommended
      as the first-line therapy for RSA of autoimmune etiologies. Furthermore, to
      elevate the percentage of successfully prevented abortions, it is advisable to
      select one of the two Sairei-to preparations (Sojyutu-Sairei-to and Byakujyutu
      Sairei-to) on the basis of differential diagnosis using the methods of Oriental
      medicine.

PMID- 20128043
TI  - Daurisoline suppressed early afterdepolarizations and inhibited L-type calcium
      current.
AB  - Our previous studies have shown that daurisoline (DS) exerted antiarrhythmic
      effects on various experimental arrhythmias. In this study, the effects of DS on
      early afterdepolarizations (EADs) and its possible mechanisms have been
      investigated. Cardiac hypertrophy was induced in rabbits by coarctating the
      abdominal aorta. The effects of DS on action potential duration (APD) and the
      incidences of EADs were studied in hypertrophied papillary muscles of rabbits in
      the conditions of low external K(+) concentration ([K(+)]o) and dofetilide (dof)
      by using standard microelectrode technique. The whole-cell patch clamp was used
      to record the L-type calcium current (I(Ca-L)) in isolated left ventricular cells
      of rabbits. The results showed that in hypertrophied papillary muscles of rabbits
      with low [K(+)]o ([K(+)]o = 2.7 mM), 1 microM dof prolonged APD(50) and APD(90)
      markedly and the incidence of EADs was 66.7% (4/6, p < 0.01); when 15 microM DS
      was applied, the incidence of EADs was 0% (0/4, p < 0.01) and the prolonged APD
      was shortened (p < 0.01). In a single myocyte, DS could also inhibit EADs induced
      by dof, low [K(+)]o and low external Mg(2+) concentration ([Mg(2+)]o)
      ([Mg(2+)](o) = 0.5 mM). DS could decrease the triangulation. In a single myocyte,
      DS could make the I-V curve upward, shift the steady-state activation curves to
      the right and the steady-state inactivation curves to the left and prolong the
      tau value of recovery curve obviously. These results suggested that DS could
      inhibit EADs which may be associated with its blockade effects on I(Ca-L).

PMID- 20128044
TI  - The anti-inflammatory effect of paeoniflorin on cerebral infarction induced by
      ischemia-reperfusion injury in Sprague-Dawley rats.
AB  - Paeoniflorin, a component in Paeonia lactiflora Pall, inhibits nuclear factor
      kappaB expression in chronic hypoperfusion rat and has anti-inflammatory
      properties. Therefore, the aim of the present study was to investigate the effect
      of paeoniflorin on cerebral infarct, and the involvement of anti-inflammation. We
      established an animal model of cerebral infarct by occluding both the common
      carotid arteries and the right middle cerebral artery for 90 min, followed by
      reperfusion of 24 hours. The ratios of cerebral infarction area to total brain
      area, and neuro-deficit score were used as an index to observe the effects of
      paeoniflorin on cerebral infarct. ED1 (mouse anti rat CD68), interleukin-1beta
      (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion
      molecular-1 (ICAM-1), myeloperoxidase (MPO) immunostaining and apoptotic cells in
      the cerebral infarction region also were studied. The results indicated that both
      pre-treatment and post-treatment with paeoniflorin reduced the ratio of cerebral
      infarction area; pre-treatment with paeoniflorin also reduced the neurological
      deficit score. The counts of ED1, IL-1beta, TNF-alpha, ICAM-1 of microvessels and
      MPO immunoreactive cells and apoptotic cells were increased in the cerebral
      infarction region; however, these increases were reduced by Paeoniflorin pre
      treatment. In conclusion, Paeoniflorin reduced cerebral infarct and neurological
      deficit in ischemia-reperfusion injured rats, suggesting that paeoniflorin may
      have a similar effect in humans and might be a suitable treatment for stroke.
      Paeoniflorin reduced cerebral infarct, at least in part, involves the anti
      inflammatory properties.

PMID- 20128045
TI  - Effects of a flavonoid extract from Cynomorium songaricum on the swimming
      endurance of rats.
AB  - The present study investigated the effects of a flavonoid extract from Cynomorium
      songaricum on the swimming endurance of rats by measuring changes of free radical
      scavenging enzymes, such as CuZn-SOD (copper, zinc-superoxide dismutase) and GSH
      px (glutathione peroxidase), and body weights. Significant and dose-dependent
      antioxidant and anti-fatigue effects of flavonoids (rutin, catechin and
      isoquercitrin) on swimming rats were observed during 10 days of swimming
      exercise. After treatment with the flavonoid extract at doses of 0.5, 1.0, and
      2.0 g/kg body weight, the CuZn-SOD and GSH-px activities in swimming rats were
      increased by 1.4%, 3.3%, 4.1% and 112.2%, 208.7%, 261.7%, respectively, while the
      levels of MDA (malondialdehyde) were decreased by 64.7%, 79.4%, and 86.4%
      respectively. Furthermore, the average body weight and the total swimming time
      were increased by 3.1%, 8.8%, 10.6%, and 7.7%, 34.5%, 61.5%, respectively. Our
      experimental results suggest that flavonoid supplementation could not only reduce
      free radical formation and scavenge free radicals, but also enhance endurance
      exercise performance by reducing muscle fatigue.

PMID- 20128046
TI  - Carbon tetrachloride-induced hepatotoxicity: Protective effect of 'Rocket' Eruca
      sativa L. in rats.
AB  - The hepatoprotective and antioxidant effect of an ethanolic extract of 'Rocket'
      Eruca sativa L. (EER), on liver injury induced by carbon tetrachloride (CCl(4))
      was investigated. Wistar albino rats were administered 250 and 500 mg/kg body
      weight extract orally for 10 consecutive days. Marker enzymes GOT, GPT, ALP, GGT
      and bilirubin were estimated in serum. Whereas, non-protein sulfhydryl (NP-SH),
      total protein (TP) and malondialdehyde (MDA) were estimated in liver tissue as
      markers for oxidative stress. Histopathological assessment was also done on liver
      tissue. CCl(4) induced liver poisoning in all treated animals was evident by
      elevated serum GOT, GPT, ALP, GGT and bilirubin levels. Induction of oxidative
      stress in the liver tissue by CCl(4) was evidenced by a fall in the levels of NP
      SH and TP; and an increased level of MDA concentration. EER administration for 10
      days prevented the CCl(4) induced hepatic injury and oxidative stress.
      Furthermore, the extract also reduced the pentobarbital-induced prolongation of
      sleeping time in mice. The ability of rocket extract to protect the liver
      toxicity in rats was further confirmed by histological findings in the liver
      tissue. In conclusion, it was observed that Eruca sativa L. extract protects the
      liver against CCl(4) induced hepatic injury through its potent antioxidant
      activity in rats.

PMID- 20128047
TI  - Estrogenic activity produced by aqueous extracts of silkworm (Bombyx mori) pupae
      in ovariectomized rats.
AB  - This study examined the estrogenic activity produced by aqueous extracts of
      silkworm (Bombyx mori) pupae in ovariectomized (OVX) rats. The components of
      silkworm pupae were extracted in distilled water at room temperature for 6 hours.
      The ovaries of six-week old female rats were then bilaterally removed. One week
      after OVX, the animals were treated with 200, 400 or 600 mg/kg/day of silkworm
      pupae extracts. The body weights of the OVX rats increased remarkably compared to
      the control rats, however their relative uterus weights to body weights decreased
      significantly. Treatment with the aqueous extracts of silkworm pupae dramatically
      improved the decreased uterus weights of OVX rats, with the highest increase
      observed in treatment with 200 mg/kg/day of the aqueous extracts. Additionally,
      treatment with aqueous extracts (200 mg/kg/day) of silkworm pupae significantly
      elevated the serum 17beta-estradiol contents of OVX rats when compared to the
      control animals. To examine the toxic effects of silkworm pupae on the hepatic
      functions of OVX rats, the levels of serum glutamate oxaloacetate transaminase
      (GOT) and glutamate pyruvate transaminase (GPT) were measured. The serum GOT and
      GPT levels did not change in response to the administration of aqueous extracts
      (200, 400 and 600 mg/kg/day) for 4-weeks. Taken together, these results suggest
      that the aqueous extracts of silkworm pupae may have estrogenic activity, which
      suggests that silkworm pupae may be useful in the prevention and/or treatment of
      menopausal disorders caused by deficiencies in female sexual hormones, including
      estrogen.

PMID- 20128048
TI  - Curcumin and saikosaponin a inhibit chemical-induced liver inflammation and
      fibrosis in rats.
AB  - Curcumin and saikosaponin A as antioxidants improve antioxidant status. This
      study investigated the anti-inflammatory and antifibrotic actions of curcumin and
      saikosaponin A on CCl(4)-induced liver damage. Sprague-Dawley rats were randomly
      divided into control, CCl(4), CCl(4)+ curcumin (0.005%; CU), CCl(4) +
      saikosaponin A (0.004%; SS), and CCl(4) + curcumin + saikosaponin A (0.005% +
      0.004%; CU + SS) groups. Carbon tetrachloride (40% in olive oil) at a dose of
      0.75 ml/kg was injected intraperitoneally once a week. Curcumin and saikosaponin
      A were supplemented alone or in combination with diet 1 week before CCl(4)
      injection for 8 weeks. After 8-week supplementation, histopathological results
      showed hepatic collagen deposition was significantly reduced in the CU and SS
      groups, and activated nuclear factor-kappa B expression induced by CCl(4) in the
      liver was significantly inhibited by curcumin and/or saikosaponin A. Hepatic
      proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6 were significantly inhibited, and anti-inflammatory cytokine
      interleukin-10 was significantly increased by supplementation with curcumin
      and/or saikosaponin A. Additionally, curcumin and/or saikosaponin A significantly
      reduced the increased levels of hepatic transforming growth factor-beta1 and
      hydroxyproline after CCl(4) treatment. Therefore, supplementation with curcumin
      and/or saikosaponin A suppress inflammation and fibrogenesis in rats with CCl(4)
      induced liver injury. However, the combination has no additive effects on anti
      inflammation and antifibrosis.

PMID- 20128049
TI  - Icariin inhibits the increased inward calcium currents induced by amyloid-beta(25
      35) peptide in CA1 pyramidal neurons of neonatal rat hippocampal slice.
AB  - Overload of intracellular calcium caused by amyloid-beta peptide has been
      implicated in the pathogenesis of neuronal damage in Alzheimer's disease. Voltage
      gated calcium channels (VGCCs) provide one of the major sources of Ca(2+) entry
      into cells. Here, we investigated whether icariin had effect on the changes of
      calcium currents induced by Abeta(25-35) in hippocampal pyramidal neurons. Using
      whole-cell patch-clamp, we showed that Abeta(25-35) enhanced the inward Ba(2+)
      and Ca(2+) currents. The currents were partially inhibited by Ni(2+) and
      completely suppressed by Cd(2+), indicating that Abeta(25-35) disrupts
      intracellular calcium homeostasis via the modulation of both L- and T-type
      channels. Furthermore, icariin nearly complete suppressed the abnormal inward
      calcium currents induced by Abeta(25-35) in a dose-dependant manner. Our findings
      suggest that the potential neuroprotective effect of icariin on Abeta(25-35)
      induced neurotoxicity via the balance intracelluar calcium homeostasis.

PMID- 20128050
TI  - Anti-inflammatory function of Nodosin via inhibition of IL-2.
AB  - In order to explore the anti-inflammatory effects of Nodosin from Isodon serra, a
      traditional Chinese herb medicine, mouse T lymphocytes were incubated with
      Nodosin. In the current study, Nodosin suppressed the overproduction of the T
      lymphocytes; moreover, cell mitosis cycle was modulated by interfering with DNA
      replication in G1 stages via inhibition of IL-2 cytokine secretion at the mRNA
      level by Nodosin. Interestingly, Xylene-induced mouse tumescence model results
      suggested Nodosin depressed the murine ear-swelling extent and the level of IL-2
      in the blood serum. Finally, Nodosin possessed significant anti-inflammatory
      effects and is a potential candidate for further clinical trial.

PMID- 20128051
TI  - Comparison of Puerariae Radix and its hydrolysate on stimulation of hyaluronic
      acid production in NHEK cells.
AB  - Hyaluronic acid (HA) is present in high concentrations in the intercellular
      spaces of the epidermis and the connective tissues of the dermis. It is
      associated with many beneficial biological activities including water retention,
      maintenance of various cellular functions, and skin homeostasis. Puerariae Radix
      (PR), a Chinese herb and a popular food in Asia, is used for various medicinal
      purposes including anti-hypertension, anti-angina pectoris and anti-dipsotropic.
      PR is rich in isoflavone glycosides like genistin and daidzin as soya. In this
      study, Bifidobactericum breve CCRC 14061 and CCRC 11846 were used for the
      fermentation of PR; moreover, acid was used to hydrolyze PR decoction. Genistein
      and daidzein in the hydrolysate were determined by HPLC. The HA production in
      normal human epidermal keratinocytes (NHEK) was measured after 48 hours
      incubation with PR and its hydrolysate, respectively. HA was assayed by enzyme
      linked immunosorbent assay (ELISA), and retinoic acid was used as the positive
      control. After fermentation with Bifidobactericum breve, the contents of daidzein
      and genistein were increased 785% and 1,010% by CCRC 14061, and 192% and 406% by
      CCRC 11846, respectively, whereas after acid hydrolysis, only daidzein was
      increased by 990%. The production of HA in NHEK was increased after incubation
      with the fermentation product of CCRC 14061, acid hydrolysate, PR decoction and
      retinoic acid (22+/- 0.2%), whereas no increase of HA concentration was found
      after incubation with the fermentation product of CCRC 11846. Furthermore, the PR
      hydrolysate stimulated the HA production of NHEK, and the effect was dose
      dependent (18.6%-83.9%). In conclusion, PR preparations would stimulate HA
      production in NHEK cells which might be used as a new cosmetic ingredient in
      moisturizers and an anti-aging agent.

PMID- 20128052
TI  - Stachydrine, a major constituent of the Chinese herb leonurus heterophyllus
      sweet, ameliorates human umbilical vein endothelial cells injury induced by
      anoxia-reoxygenation.
AB  - Stachydrine is a major constituent of Chinese herb leonurus heterophyllus sweet,
      which is used in clinics to promote blood circulation and dispel blood stasis.
      Our study aimed to investigate the role of stachydrine in human umbilical vein
      endothelial cells (HUVECs) injury induced by anoxia-reoxygenation. Cultured
      HUVECs were divided randomly into control group, anoxia-reoxygenation (A/R) group
      and 4 A/R+stachydrine groups. HUVECs in the control group were exposed to
      normoxia for 5 hours, while in all A/R groups, HUVECs underwent 3 hours anoxia
      followed by 2 hours reoxygenation, and HUVECs in the 4 A/R+stachydrine groups
      were treated with 10(-8) M, 10(-7) M, 10(-6) M and 10(-5) M (final concentration)
      of stachydrine respectively. After anoxia-reoxygenation, tissue factor (TF) was
      over-expressed, cell viability and the concentrations of SOD, GSH-PX and NO were
      declined, while LDH, MDA and ET-1 were over-produced (p < 0.05 to 0.001 vs. the
      control group). However, in stachydrine treated groups, TF expression was
      inhibited at both mRNA and protein levels, while the declined cell viability and
      SOD, GSH-PX, NO as well as the enhanced LDH, MDA and ET-1 levels occurred during
      anoxia-reoxygenation were ameliorated and reversed effectively (p < 0.05 to 0.01
      versus A/R group). Consequently, our findings indicate that TF plays an important
      role in the development of anoxia-reoxygenation injury of HUVECs, stachydrine
      ameliorates HUVECs injury induced by anoxia-reoxygenation and its putative
      mechanisms are related to inhibition of TF expression.

PMID- 20128053
TI  - Effects of herbal medicinal formulas on suppressing viral replication and
      modulating immune responses.
AB  - The Chinese medicinal herbs Radix Isatidis and Viola yedoensis Makino have been
      suggested to possess antiviral activity. This study tests whether these and other
      Chinese and Western herbal medicinal formulas can modulate the immune functions
      involving virus-suppression in BALB/c mouse. We first confirmed the extract from
      Viola yedoensis Makino, but not from Radix Isatidis, the traditional Chinese
      medicine (TCM) formula Chui-Uren-Chien (CUC), or a Western homeopathic medicinal
      drink Metodo Canova, could inhibit the replications of herpes simplex virus-1 and
      enterovirus 71 in the human neuroblastoma SK-N-SH cell line. Subsequently, the
      same herbal extracts and drink underwent toxicity and immunomodulatory tests on
      mice of 5-7 weeks old. After 8 weeks of feeding different herbal medicinal
      formulas, no hepatic or renal toxicity was noted in any tested animal; whereas
      among the immune function evaluations, only the mice treated with CUC extract
      were found to be associated with significant increases (p < 0.05) in both the
      level of plasma IgG and the percentage of monocyte in blood mononuclear cells as
      well as the activation of macrophage Raw264.7 cells for nitric oxide production,
      suggesting its role in modulating the non-specific immune response. Analyses
      using protein arrays showed CUC was the most potent herbal medicinal formula
      eliciting fluctuations in plasma cytokine and chemokine concentrations. Taking
      all experimental data together, we conclude Chui-Uren-Chien possesses
      immunomodulatory capability in mouse, but none of the herbal medicinal formulas
      tested here are involved in strengthening antiviral immunity.

PMID- 20128054
TI  - Purification, characterization and immuno-modulating properties of
      polysaccharides isolated from Flammulina velutipes mycelium.
AB  - To investigate the immuno-modulating activity of Flammulina velutipes mycelium,
      three different Flammulina velutipes polysaccharides (FVPs) were isolated by
      fractionation using gel filtration and were identified as the immunomodulators of
      murine peritoneal macrophages. Based on the results of fourier transform infrared
      spectroscopy (FTIR), high performance liquid chromatography (HPLC), NMR
      spectroscopy, methylation analysis and gas chromatography-mass spectrogram (GC
      MS), FVP2C was identified as glucose, galactose, mannose and fucose in molar
      ratio of 100: 14: 7: 4. FVP2C, molecular weight of 27.3 x 10(3) Da, was
      characterized as alpha-D-(1-->4)-glucan which was highly branched with alpha-D-(1
      ->6)-glucosyl residues, a single galactose or small amounts of mannoses and
      fucose at the C-6 position every twelve residues, on average, along the main
      chain. In the present study, it was found that three FVPs induced a significant
      increase in cellular nitric oxide formation, interleukin-1 production and tumor
      necrosis factor-alpha secretion in macrophages in vitro. The immuno-modulating
      activity of FVP2A, FVP2B and FVP2C was dose-dependent.

PMID- 20128055
TI  - Evaluation of the cultivation age of dried ginseng radix and its commercial
      products by using (1)H-NMR fingerprint analysis.
AB  - The perfect ginseng radix is collected when the ginseng root reaches a
      cultivation age of six years; this ensures the best mass quality and consistency
      of the plant's essential bioactive components. Since traditional means of
      authentication via physical appearance or smell are hardly reliable, an efficient
      analytical method that can determine the real cultivation age of dried ginseng
      radix in commercial products, especially ginseng products of various dosage
      forms, is urgently required. In the present study, chemical fingerprint by (1)H
      NMR spectroscopy was used on dried ginseng radix samples with cultivation ages
      ranging from 1-6 years. The resulting dataset was then analyzed by using
      principle component analysis and cluster analysis to build up a distributive
      model that allows the identification of the real cultivation age of the ginseng
      radix based on a plant metabolomic strategy. This quality surveillance method was
      able to clearly discriminate the 6 years old ginseng radix from the other ages,
      and could be applied on the evaluation of the real cultivation age for the
      various dried white ginseng radix samples and commercial products accurately.

PMID- 20128056
TI  - Integrated care. The right time to go local.

PMID- 20128058
TI  - New service. Starting from scratch.

PMID- 20128057
TI  - Autonomous units. A toolkit for autonomy.

PMID- 20128059
TI  - Workforce. Total teamwork.

PMID- 20128060
TI  - Renal procurement. A vision built to last.

PMID- 20128061
TI  - Patient experience. Bringing care closer.

PMID- 20128062
TI  - CQC calls in high ranking fixer for 'chaotic' trust registration process.

PMID- 20128063
TI  - Patient safety. Campaign for courage underway at Mid Staffs.

PMID- 20128064
TI  - Sophia Christie on a crumbling model.

PMID- 20128065
TI  - Hear the wisdom of the troops.

PMID- 20128066
TI  - Productivity challenge. Feeling the squeeze: how to maximise the year ahead.

PMID- 20128067
TI  - Collaboration. Bright lights, big cities: sharing best practice.

PMID- 20128068
TI  - Proper entry point for femoral intramedullary guide in total knee arthroplasty.
AB  - BACKGROUND: Postoperative tibiofemoral alignment of the lower extremity is one of
      the most important factors that will assure a successful long-term outcome of a
      total knee arthroplasty. In this regard, most surgeons prefer to use an
      intramedullary guide than an extramedullary one for the femoral cut. However the
      entry point for the guiding rod is crucial for an appropriate femoral cut and
      femoral component positioning. The ideal entry point of the guiding rod should be
      the central axis of the distal femur in both coronal (anterior view) and sagittal
      planes (lateral view). OBJECTIVE: The authors studied the proper entry point for
      the femoral intramedullary guiding rod in total knee arthroplasty by using the
      top of the femoral intercondylar notch as the referenced point. MATERIAL AND
      METHOD: A series of radiographs for twenty-nine femurs from thirty-one cadavers,
      both anterior-posterior and lateral views, were evaluated in this study. RESULTS:
      75.8 percent of the entry points in the coronal plane were at least 1 mm medial
      to the top ofthefemoral intercondylar notch. 82.7 percent of the entry points in
      the sagittal plane were superior to the top of the femoral intercondylar notch
      more than 10 mm. The proper entry point at the distal femur should be 1.5 +/-
      2.01 mm medial and 12 +/- 2.72 mm superior to the top of the femoral
      intercondylar notch. CONCLUSION: The result of this study could be useful for
      surgeons who prefer intramedullary guide system in total knee arthroplasty.

PMID- 20128069
TI  - Prediction of deep vein thrombosis after total knee arthroplasty with
      preoperative D-dimer plasma measurement.
AB  - BACKGROUND: Despite prophylaxis, deep vein thrombosis (DVT) still occurs
      frequently after elective knee surgery. Hence, it would be helpful if the high
      risk DVT patients could be identified before surgery so the adequate prophylaxis
      could be given. A normal plasma D-dimer level effectively rules out acute DVT
      patients who were classified as having low clinical probability. In many studies,
      one coagulation activation marker was measured to observe their role in
      preoperative prediction ofDVT after major hip or knee surgery. In this study, the
      preoperative plasma level of D-dimer in patients undergoing total knee
      arthroplasty (TKA) was collected, and correlated with the results of
      postoperative venography OBJECTIVE: To determine whether levels of D-dimer in
      plasma, taken two weeks preoperatively, predicts the development of DVT in
      patients undergoing TKA. MATERIAL AND METHOD: Fifty-nine consecutive patients
      undergoing TKA were seen in a preoperative clinic two weeks prior the surgery and
      had blood taken for measurement of plasma D-dimer. After surgery, they did not
      receive prophylaxis anticoagulant. Ascending contrast venography of both lower
      extremities was performed in all cases between the 6th-l0th postoperative day or
      earlier if clinical symptoms occurred. RESULTS: Plasma D-dimer was measured
      preoperatively in 59 patients undergoing TKA. DVT was detected by venography in
      31 (53%) patients. At a cutoff or 500 ng/ml, the sensitivity, specificity,
      positive and negative predictive values of the preoperative D-dimer concentration
      for the development of subsequent DVT were 58%, 46%, 55%, and 50%, respectively.
      CONCLUSION: The results of the present study suggested that preoperative plasma
      measurement of D-dimer concentration is not useful for predicting DVT in patients
      undergoing TKA.

PMID- 20128070
TI  - Gastrointestinal and cardiovascular risk of non-selective NSAIDs and COX-2
      inhibitors in elderly patients with knee osteoarthritis.
AB  - OBJECTIVE: To evaluate the incidence and risk profiles for gastrointestinal (GI)
      events and cardiovascular (CV) events in elderly patients (aged > or =60 years)
      with knee osteoarthritis using tNSAIDs (traditional non-steroidal anti
      inflammatory drugs) or coxibs users in patients with knee osteoarthritis aged >
      or =60 years. MATERIAL AND METHOD: A hospital-based retrospective cohort study
      was applied. Data on prescription drug (NSAIDs, celecoxib, etoricoxib) was
      obtained from hospital database. Data on CV events and GI adverse events was
      obtained from the registry of the Cardiology Unit and Gastroesophagoscope
      Diagnosis Center, GI Center, Department of Internal medicine, Police General
      Hospital. Patients visiting the hospitals' outpatient clinics from June 2004 to
      June 2007 were included if they were aged > or =60 years and received at least
      one follow-up visit on the prescription of a tNSAIDNSAID or coxibs (etoricoxib or
      celecoxib). Patients with a history of gastrointestinal disease or heart disease
      were excluded. All patients were followed-up from their first visit to the date
      of their earliest event or to the end of the study period. The interested event
      was assumed to be attributed to the last prescription shown in the study period.
      RESULTS: A total 12,591 prescriptions from 1030 patients, an average of 4
      prescriptions/patient/year, were screened -3,982 (31.6%) prescriptions were for
      NSAIDs, 4426 (35.2%) were for celecoxib, and 4183 (33.2%) were for etoricoxib.
      The most common traditional NSAID prescribed was meloxicam (24%), followed by
      nimesulide (21.4%) and naproxen (13.1%). The mean age of cohort was 69.6 years,
      with the majority being female (74%). We found a comparable dose of celecoxib
      (200 mg OD) and etoricoxib (90 mg OD) prescribed in the respective patients. A
      total of 78 gastrointestinal events occurred and Esophagogastroscopy indicated
      that 37 (47.4%) were dyspepsia, 22 (28.2%) were anemia (28.2%), 17 (21.7%) were
      upper GI bleeding, and 2 (2.6%) were others. Forty (40) of these events were
      attributed to NSAIDs, 21 to celecoxib and 17 to etoricoxib. Observed GI events
      included gastritis (50, 64.1%), gastric ulcer (14, 17.9%), duodenal ulcer (3,
      3.8%), and normal (11, 14.1%). Patients receiving traditional NSAIDs, celecoxib
      and etoricoxib had 20, 18, and 11 CV events respectively. Of these 49 CV events,
      the most common was heart failure (20), followed by chronic heart failure (9),
      angina pectoris (9), unstable angina (6), and myocardial infarction (5).
      Comparing celecoxib with NSAID use in logistic regression analysis, patients who
      received celecoxib were significantly less likely to suffer GI events than those
      who received NSAIDs; OR = 0.36 (95% CI 0.21-0.63, p = 0.00.). Similarly,
      etoricoxib was less likely to cause GI events than NSAIDs; OR = 0.52 (95% CI 0.28
      0.98, p = 0.04). Comparing to patients aged under 60 years, patients aged >70
      years had a significantly higher chance of developing GI events, OR = 1.79 (95%
      CI 1.13-2.4) for patients aged 70-80 years and 3.36 (95% CI 1.78-5.81) for those
      aged > 80 years. Drug exposure time, which was defined as the number of days of
      medication supplied significantly increased the GI risks. For CV event, there
      were only 3 significantly associated with CV events -female (OR = 0.29, 95% CI
      0.16-0.59, p = 0.00), age >80 years (OR = 2.98, 95% CI 1.57-4.23, p = 0.00), and
      drug exposure time (OR = 1.05, 95% CI 1.02-1.54, p = 0.00). CONCLUSION: Incidence
      of GI and CV events was lower for coxibs than for NSAIDs and celecoxib had a
      lower incidence than etoricoxib. Patients with advanced age and higher drug
      exposure time had a significantly increased risk ofGI; the use of
      gastroprotective agents significantly decreased GI risks. Being female, advanced
      age, and drug exposure time significantly affected CV events.

PMID- 20128071
TI  - Association of estrogen receptor-alpha single-nucleotide polymorphism (codon 594
      G-->A) and Thai patients affected by knee osteoarthritis.
AB  - BACKGROUND: Estrogen receptor-alpha single-nucleotide polymorphism (ER-alpha SNP)
      has previously shown its susceptibility to knee osteoarthritis (OA) but this
      association cannot be applied to ethnic groups with different genetic
      backgrounds. OBJECTIVE: To characterize the genetic association between ER-alpha
      SNP and knee OA in the Thai. MATERIAL AND METHOD: A case-control study was
      conducted at Ramathibodi Hospital from August 2007 to May 2008. Altogether, 104
      cases affected by knee OA and 104 controls were included in this study. SNP
      rs2228480 (codon 594 G!A) on the ER-alpha gene was genotyped by a PCR-RFLP-based
      technique. Genotype frequencies were analyzed by logistic regression. RESULTS: ER
      alpha SNP was normally distributed through the Hardy-Weinberg Equilibrium (HWE).
      The risk of knee OA was genetically associated to AG an AA genotypes compared
      with homozygous wild-type GG (OR: 1.02, 95% CI: 0.60-1.80 for AG; OR: 1.27, 95%
      CI: 0.30-4.90 for AA). CONCLUSION: Our study showed that these genetic
      alterations might be associated with knee osteoarthritis in the Thai population.
      Further investigation on other informative SNPs on the ER-alpha gene should be
      performed to create a reliable haplotype that might provide a stronger link
      between genetic profiles and clinical picture.

PMID- 20128072
TI  - The landmarks of centers of the distal femur and the proximal tibia in sagittal
      plane for application in computer assisted total knee arthroplasty.
AB  - BACKGROUND: In the computer assisted total knee arthroplasty (CAS-TKA), the
      centers of the distal femur and the proximal tibia for the sagittal mechanical
      axis (SMA) of both femur and tibia have unclear references. Most CAS-TKA systems
      define both centers following the engineer's recommendation. OBJECTIVE: To
      evaluate the centers of the distal femur and the proximal tibia in sagittal plane
      and to determine the sagittal mechanical axis (SMA) of the normal knee in
      relation to the Blumensaat's line and the tibial anteroposterior line. MATERIAL
      AND METHOD: Fifty five normal healthy knees without flexion contracture or
      hyperextension were enrolled. The sagittal mechanical axis (SMA) was drawn from
      the center of the femoral head to the most prominent dome of the talus on the
      long standing hip-knee-ankle radiograph in lateral view. The point that the SMA
      passed the Blumensaat's line of distal femur and the tibial plateau at the
      proximal tibia were reported as the percentage of the total length of
      Blumensaat's line and of the anteroposterior width of tibial plateau r
      respectively. RESULTS: Among 55 knees included in this study, 32 knees were right
      side and 23 knees were left sided. Of which, there were 14 females and 41 males.
      Their average age was 45 years. The average BMI was 25.67. The average knee
      alignment in sagittal plane was 1.7 degrees. At the distal femur, the point that
      SMA passed the Blumensaat's line was average 13% of the total length of
      Blumensaat's line. There were only 22% of the 55 knees that the SMA passed at the
      tip of Blumensaat's line. All of SMA in 55 knees passed within the first quarter
      of this line. At the proximal tibia, the point that SMA passed the tibial plateau
      average 45% of the anteroposterior width of tibial plateau. CONCLUSION: The
      center of distal femur and proximal tibia on sagittal plane are not individual
      consistent. Therefore, they should be evaluated preoperatively before performing
      the CAS TKA to prevent the incorrect bone cutting, prosthesis malposition and
      poor soft tissue balance in sagittal plane.

PMID- 20128073
TI  - Effects of posterior cruciate ligament resection in total knee arthroplasty using
      computer assisted surgery.
AB  - OBJECTIVE: The authors prospectively measure the effects of Posterior Cruciate
      Ligament (PCL) excision in Total Knee Arthroplasty (TKA) using Computer Assisted
      Surgery (CAS). MATERIAL AND METHOD: Between April 2008 and June 2008, sixteen
      knees of fifteen patients with varus deformity less than 20 degree and grossly
      intact PCL were included in this study. Using CAS and tensioning device to
      maintain consistent pressure, extension and flexion gap on both medial and
      lateral side before and after resection of PCL was recorded. RESULTS: The mean
      increases of extension gap on medial and lateral side after resection of PCL are
      0.17 +/- 0.22 mm (-0.17 to 0.5 mm) and 0.25 +/- 0.37 mm (-0.33 to 1.16 mm)
      respectively. The mean increases of flexion gap on medial and lateral side are
      1.29 +/- 1.02 mm (0-3 mm) and 2.09 +/- 1.12 (0.5-4.66 mm) respectively.
      CONCLUSION: Resection of PCL showed increase of flexion gap more than extension
      gap (p-value < 0.05) and lateral side of flexion gap always increase more than
      medial side (p-value < 0.05).

PMID- 20128074
TI  - Accuracy of knee implants sizing predicted by digital images.
AB  - BACKGROUND: Accurate preoperative templating to predict implant size and position
      can facilitate precise, efficient, and reproducible knee replacement operations.
      Preoperative templating for total knee arthroplasty can be performed with digital
      images of the knee implants on digital radiographs of the knee. OBJECTIVE: To
      determine the accuracy of knee implants sizing predicted by digital images.
      MATERIAL AND METHOD: A retrospective study was done to assess the accuracy of the
      knee implant sizing predicted by digital images in 100 Thai adults, who had
      osteoarthritis of the knee. Digital anteroposterior and lateral radiographs of
      the knee were used in measuring the level of distal femoral resection and the
      level of proximal tibial resection. Anteroposterior and mediolateral diameter of
      femur and tibia were determined and the implant size was choosen. The results
      from digital images were compared with the size of actual femoral and tibial
      implants used at the time of surgery. All variables were analyzed. The
      correlation coefficients were calculated to determine interobserver and
      intraobserver reliability. RESULTS: The accuracy of digital preoperative plans
      for femoral component was 53.1%. The accuracy of digital preoperative plans for
      tibial component was 59.3%. The digital preoperative planning predicted 79 of 81
      (97.6%) femoral implants to within one size and predicted 77 of 81 (95.1%)
      measurements of the tibial implants to within one size. CONCLUSION: Digital
      images can help to focus the thoughts and plans of the operation. When planning
      is performed, it can identify extremes of sizes that may require special order,
      and planning can predict size mismatches between femoral and tibial implants.
      When recognized ahead of time, these limitations can be accommodated during the
      surgical procedure or a different implant system chosen. Predicting implant sizes
      to within one size allows efficient anticipation by the orthopaedic surgeon.

PMID- 20128075
TI  - Open-wedge high tibial osteotomy in varus knee osteoarthritis: a 5-year
      prospective cohort study.
AB  - BACKGROUND: High tibial osteotomy (HTO) is an accepted procedure to correct the
      varus deformity to restore the mechanical axis, reduce pain and delay the need
      for arthroplasty, especially in young and active patients. Nowadays, the opening
      wedge HTO is preferable than the close one. OBJECTIVE: To evaluate the clinical
      results and complications of medial compartment gonarthrosis treated with opening
      wedge HTO. MATERIAL AND METHOD: The prospective cohort study of 45 knees in 40
      consecutive patients (32 women, 8 men, 46-81 years) with medial compartment
      osteoarthritis of the knee underwent medial open-wedge HTO and TomoFix between
      February 2004 and February 2009 (average follow-up of 46.1 +/- 11.5 months).
      RESULTS: During the follow-up period, patients experienced significantly greater
      pain relief from baseline pain-intensity scores (all p < 0.001). The mean
      femorotibial angle (FTA) at the preoperative, 1-year and more than 2-year follow
      up were 171.27 +/- 9.41 degrees of varus, 182.91 +/- 4.93 and 182.45 +/- 5.74
      degrees of valgus, in orderly. CONCLUSION: Medial opening wedge HTO with TomoFix
      provided intraoperative desirable correction and sufficient stabilization. Early
      mobilization, rehabilitation and maintenance of correction alignment until bony
      union occurred without instrument failure.

PMID- 20128076
TI  - Radical plans. Labour plan puts adult social care in NHS hands as ministers seek
      savings.

PMID- 20128077
TI  - Patient safety. Experts attack plans for mandatory error reports.

PMID- 20128078
TI  - Monitor and CQC. Both regulators leaderless as Young quits CQC.

PMID- 20128079
TI  - Conservative policy. Tory pledge on targets might not hit the spot.

PMID- 20128080
TI  - Stephen Eames on the three card trick.

PMID- 20128081
TI  - On mental health. Modern services are moving on.

PMID- 20128082
TI  - Rheumatology. Hitting hard, hitting fast.

PMID- 20128084
TI  - Too little, too late. Poor GP and public awareness leads to delays in diagnosis
      and treatment.

PMID- 20128083
TI  - Advances. A new era in treating arthritis.

PMID- 20128085
TI  - Finance. The disease that crosses spending boundaries.

PMID- 20128086
TI  - Developing policy. A path to quality services.

PMID- 20128087
TI  - Human resources. How to defeat procrastination.

PMID- 20128088
TI  - Leadership training. Managers on a mission in Sandhurst manoeuvres.

PMID- 20128089
TI  - Efficiency. A costing system where every patient counts.

PMID- 20128090
TI  - Legal. Take a closer look at potential staff.

PMID- 20128091
TI  - Job cuts could see up to 5,700 staff go from PCT and SHA management.

PMID- 20128092
TI  - MRSA latest target removes lower threshold for accountability. PCTs could
      struggle to hit infection 'objective'.

PMID- 20128093
TI  - Review of 2009. A swine of a year for Mid Staffs, Rose Gibb and the public purse.

PMID- 20128094
TI  - On top leaders. Cream of the crop rises to the top.

PMID- 20128095
TI  - Human resources. How trusts can raise their sights.

PMID- 20128096
TI  - Finance. Principles and practice of provider economics.

PMID- 20128097
TI  - Service redesign. How regional units take the crisis out of trauma.

PMID- 20128098
TI  - Technology. A quality shift in staff rostering.

PMID- 20128099
TI  - Pre-budget report. The phoney war continues.

PMID- 20128100
TI  - Managers' views. The day the NHS stood still.

PMID- 20128101
TI  - Efficency. Tougher than it has ever been. Interviewed by Sally Gainsbury.

PMID- 20128102
TI  - Neil Griffiths on the push for productivity.

PMID- 20128103
TI  - Total place. Pooling power.

PMID- 20128104
TI  - Pay. Unkind cuts.

PMID- 20128105
TI  - Learning from Binayak Sen: doctors as advocates of the poor and marginalized.

PMID- 20128106
TI  - Increase in membrane thickness during development compensates for eggshell
      thinning due to calcium uptake by the embryo in falcons.
AB  - We compared membrane thickness of fully developed eggs with those of non
      developed eggs in different endangered falcon taxa. To our knowledge, membrane
      thickness variation during development has never been examined before in falcons
      or any other wild bird. Yet, the egg membrane constitutes an important protective
      barrier for the developing embryo. Because eggshell thinning is a general process
      that occurs during bird development, caused by calcium uptake by the embryo, eggs
      are expected to be less protected and vulnerable to breakage near the end of
      development. Thus, egg membranes could play an important protective role in the
      later stages of development by getting relatively thicker. We used linear mixed
      models to explore the variation in membrane thickness (n = 378 eggs) in relation
      to developmental stage, taxon, female age, mass and identity (73 females), egg
      laying sequence (105 clutches) and the study zone. Our results are consistent
      with the prediction that egg membranes are thicker in fully developed eggs than
      in non-developed eggs, suggesting that the increase in membrane thickness during
      development may compensate for eggshell thinning. In addition, our data shown
      that thicker membranes are associated with larger, heavier and relatively wider
      eggs, as well as with eggs that had thinner eggshells. Egg-laying sequence,
      female age and the study zone did not explain the observed variation of membrane
      thickness in the falcon taxa studied. As we provide quantitative data on membrane
      thickness variation during development in falcons not subjected to contamination
      or food limitation (i.e. bred under captive conditions), our data may be used as
      a reference for studies on eggs from natural populations. Considering the large
      variation in membrane thickness and the multiple factors affecting on it and its
      importance in the protection of the embryo, we encourage other researchers to
      include measurements on membranes in studies exploring eggshell thickness
      variation.

PMID- 20128107
TI  - Parental conflict and blue egg coloration in a seabird.
AB  - When both parents provide offspring care, equal sharing of costly parental duties
      may enhance reproductive success. This is crucial for longlived species, where
      increased parental effort in current reproduction profoundly affects future
      reproduction. Indication of reproductive value or willingness to invest in
      reproduction may promote matching responses by mates, thus reducing the conflict
      over care. In birds with biparental care, blue-green eggshell color may function
      as a signal of reproductive value that affects parental effort, as predicted by
      the signaling hypothesis of blue-green eggshell coloration. However, this
      hypothesis has not been explored during incubation, when the potential stimulus
      of egg color is present, and has been little studied in longlived birds. We
      experimentally studied if egg color affected incubation patterns in the blue
      footed booby, a longlived species with biparental care and blue eggs. We
      exchanged fresh eggs between nests of the same laying date and recorded parental
      incubation effort on the following 4 days. Although egg color did not affect male
      effort, original eggshell color was correlated with pair matching in incubation.
      Exchanged eggshell color did not affect incubation patterns. This suggests that
      biliverdin-based egg coloration reflects female quality features that are
      associated with pair incubation effort or that blue-footed boobies mate
      assortatively high-quality pairs incubating more colorful clutches. An intriguing
      possibility is that egg coloration facilitates an equal sharing of incubation,
      the signal being functional only during a short period close to laying. Results
      also suggest that indication of reproductive value reduces the conflict over
      care.

PMID- 20128108
TI  - Disease-specific quality of life in children and adults with anorectal
      malformations.
AB  - PURPOSE: The aim of the present study was to analyze disease-specific quality of
      life, as assessed by the Hirsch-sprung Disease/Anorectal Malformation Quality of
      Life (HAQL) questionnaire, in children and adults with ano-rectal malformations
      (ARM). METHODS: As much as 175 children and 62 adults who were members of the
      Italian Association for Anorectal Malformations were asked to complete the
      Italian version of the HAQL questionnaire developed for this study. For children
      under 16 years of age, mothers were asked to fill up the questionnaires. Patients
      were also asked to identify their type of malformation from a list of eight
      choices. RESULTS: Most subscales of the Italian HAQL had acceptable reliability.
      Compared to children, adults reported significantly lower levels of QL on
      subscales measuring emotional functioning, body image, and physical symptoms.
      CONCLUSIONS: Longitudinal studies are needed to clarify whether these results can
      be attributed to improvements in surgical techniques that have contributed to
      improved QL in younger cohorts, or if, instead, quality of life in patients with
      ARM decreases over time. Intervention efforts should focus on bowel management
      and psychological treatment for ARM-related emotional and body image distress.

PMID- 20128109
TI  - Application with repeated serum biomarkers in pediatric  appendicitis in clinical
      surgery.
AB  - PURPOSE: To apply the repeated serum laboratory tests in diagnosing acute
      appendicitis in children with suspected appendicitis. METHODS: From 2005 to 2007,
      we prospectively collected 217 pediatric patients with clinically suspected
      appendicitis. The repeated serum laboratory tests were measured 6 h later and the
      changes in serum inflammatory biomarkers analyzed. Significant changes in serum
      parameters between primary and repeated examinations were selected as the
      discriminating variables. The receiver operating characteristic (ROC) curves were
      used to determine the cutoff values of the changes between two examinations in
      predicting appendicitis. RESULTS: Based on the ROC analysis, the change in the
      serum parameters could include simple appendicitis when the change in neutrophils
      (delta neutrophils) was >23.5% and delta C-reactive protein (CRP) was >118 mg/L;
      but for the exclusion of simple appendicitis, delta neutrophils was -44% or under
      and delta CRP was -10.0 mg/L or under. For perforated appendicitis, delta white
      blood cell counts, delta neutrophils, delta bands and delta CRP were all
      significant discriminators. However, based on analysis of the area under the ROC
      curve (AUC), only delta CRP had the greatest AUCs in predicting both simple and
      perforated appendicitis. The cutoff point of delta CRP was taken as 4.80 mg/L in
      distinguishing simple appendicitis from other acute abdominal diseases, and taken
      as 9.45 mg/L in predicting perforated appendicitis. CONCLUSIONS: Significant
      change between primary and repeated serum laboratory tests may serve as a helpful
      method in predicting acute appendicitis in children with suspected appendicitis.

PMID- 20128110
TI  - Effect of leflunomide on liver regeneration after partial hepatectomy in rats.
AB  - PURPOSE: Partial hepatectomy (PH) can be an inevitable surgical therapy in some
      conditions, such as hepatic malignancies, trauma or partial liver
      transplantation. Its capacity for regeneration distinguishes the liver from other
      essential organs. Regeneration is a complex process involving growth factors,
      cytokines, transcription factors, hormones, and oxidative stress products. In the
      event of ineffective or total absent liver regeneration, the life threatening
      picture of acute liver failure may supervene. In the present research, we studied
      the effect of leflunomide, a novel immunosuppressive and antiinflammatory agent
      against autoimmune disease, on hepatic regeneration after PH in Wistar Albino
      rats. METHODS: Thirty-five Wistar albino rats were divided into five groups:
      group 1, control; group 2, sham; group 3, drug control (was treated with
      leflunomide 10 mg/kg/d/i.g.); group 4, PH; group 5, PH + leflunomide. As for PH,
      approximately 70% of the rat liver was surgically removed under general
      anesthesia. On postoperative day 3, all rats were humanely killed. Catalase
      (CAT), superooxide dismutase (SOD) and myeloperoxidase (MPO) activities with
      malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were
      determined in remnant liver tissue. Inflammatory process and liver regeneration
      were evaluated with H&E and KI67, respectively. RESULTS: The tissue levels of
      MDA, PC and MPO were lower in group 5 than levels in group 1. PH significantly
      decreased the enzymatic activity of CAT (p < 0.05) and SOD. This reduction was
      significantly improved by the treatment with leflunomide. Histopathologically the
      enhancement of the liver parenchymal regeneration in the group 5 was
      significantly greater than the group 4. CONCLUSION: The findings imply that
      oxidative stress products play a preventive role in liver regeneration after PH
      and leflunomide ameliorates the regeneration probably by the radical scavenging
      and antioxidant activities.

PMID- 20128111
TI  - Submucosal fibrin glue injection for closure of recurrent tracheoesophageal
      fistula.
AB  - We describe a new endoscopic technique for closure of recurrent tracheoesophageal
      fistula in which fibrin glue is injected into the submucosa of the lateral walls
      of the fistula until the lumen is occluded. This technique eliminates the
      possibility of the fibrin glue plug becoming dislodged and aspirated. In
      addition, our technique is simpler and safer in that it does not require
      diathermy or laser coagulation to deepithelialize the tract, and thereby
      eliminates the potential for injury to the esophagus and trachea.

PMID- 20128112
TI  - Exploring the relationship between diabetes self-efficacy, depressive symptoms,
      and glycemic control among men and women with type 2 diabetes.
AB  - Depression and low self-efficacy are both associated with worse glycemic control
      in adults with diabetes, but the relationship between these variables is poorly
      understood. We conducted a cross-sectional study examining associations between
      depressive symptoms, self-efficacy, and glycemic control among men (n = 64) and
      women (n = 98) with type 2 diabetes to see if self-efficacy mediates the
      relationship between depression and glycemic control. Correlational and
      mediational analyses examined the relationship between these three variables for
      the sample as a whole and separately by sex. A significant association between
      depressive symptoms and glycemic control was found for men (0.34, P < 0.01) but
      not for women (0.05, P = 0.59). Path analysis suggested that, among men, self
      efficacy mediates the relationship between depressive symptoms and glycemic
      control. We conclude that men with depressive symptoms and type 2 diabetes may
      need tailored interventions that improve their self-efficacy in order to achieve
      glycemic control.

PMID- 20128113
TI  - Geographic and molecular variation in a natural plant transgene.
AB  - A PCR based survey of Festuca ovina plants from populations around the southern
      part of the Baltic Sea demonstrates both geographic and molecular variation in
      the enzyme gene PgiC2, horizontally transferred from a Poa-species. Our results
      show that PgiC2-a natural functional nuclear transgene-is not a local ephemeral
      phenomenon but is present in a very large number of individuals. We find also
      that its frequency is geographically variable and that it appears in more than
      one molecular form. The chloroplast variation in the region does not indicate any
      distinct subdivision due to different colonization routes after the last
      glaciation. Our data illustrate the geographic and molecular variation that may
      occur in natural populations with a polymorphic, unfixed transgene affected by
      diverse kinds of mutational and evolutionary processes.

PMID- 20128115
TI  - [Airtraq laryngoscope as an alternative to fiberoptic tracheal intubation in the
      awake patient].

PMID- 20128116
TI  - Information from your family doctor. Drug warnings: is my medicine safe?

PMID- 20128114
TI  - Genetic divergence among sympatric colour morphs  of the Dalmatian wall lizard
      (Podarcis melisellensis).
AB  - If alternative phenotypes in polymorphic populations do not mate randomly, they
      can be used as model systems to study adaptive diversification and possibly the
      early stages of sympatric speciation. In this case, non random mating is expected
      to support genetic divergence among the different phenotypes. In the present
      study, we use population genetic analyses to test putatively neutral genetic
      divergence (of microsatellite loci) among three colour morphs of the lizard
      Podarcis melisellensis, which is associated with differences in male morphology,
      performance and behaviour. We found weak evidence of genetic divergence,
      indicating that gene flow is somewhat restricted among morphs and suggesting
      possible adaptive diversification.

PMID- 20128117
TI  - Information from your family doctor. Erectile dysfunction.

PMID- 20128119
TI  - [The culture of daily life in occupied France].

PMID- 20128120
TI  - Literature and morality.

PMID- 20128121
TI  - [Village life in Vichy France].

PMID- 20128122
TI  - ["Speak to me of love": sentimental romance literature as a form of escape from
      the realities of daily life, 1939-42?].

PMID- 20128123
TI  - Family strategies: patterns of inheritance in Odiham, Hampshire, 1525-1850.

PMID- 20128124
TI  - Nineteenth-century urban Greek households: the case of Hermoupolis, 1861-1879.

PMID- 20128125
TI  - Bastardy and the great famine: Ireland, 1845-1850.

PMID- 20128127
TI  - Age-based rationing of medical care in nineteenth-century England.

PMID- 20128128
TI  - Household, family and welfare: past, present and future.

PMID- 20128129
TI  - Back to the basics: mortality and fertility interactions during the demographic
      transition.

PMID- 20128130
TI  - Borders, ethnicity, and demographic patterns in the Russian Baltic provinces in
      the late nineteenth century.

PMID- 20128131
TI  - The social mobility of servants in rural Sweden, 1740-1894.

PMID- 20128132
TI  - Unnatural infertility, or, whatever happened in Colyton? Some reflections on
      "English Population History from Family Reconstitution 1580-1837".

PMID- 20128133
TI  - The limitations of English family reconstitution: "English Population History
      from Family Reconstitution 1580-1837".

PMID- 20128134
TI  - Progress through existing technology.

PMID- 20128135
TI  - [The Second Hungarian-Romanian Conference of Pneumology, Szeged, Hungary,
      November 6-9, 2009].

PMID- 20128136
TI  - [The Fifth Romanian Conference of Bronchology, Timisoara, November 12-14, 2009].

PMID- 20128137
TI  - The story of the progress reports on research into gene therapies for Duchenne
      muscular dystrophy.

PMID- 20128138
TI  - The progress reports on the development of therapies of Duchenne muscular
      dystrophy.
AB  - The roots of the progress reports on the development of therapies for Duchenne
      muscular dystrophy (DMD) that since 2000 have been produced at Breitnau/Germany
      and distributed to the parents of DMD patients cover over 30 years of continual
      occupation with this disease. The beginning was marked by the development of an
      early detection programme for the genetic disposition for DMD in infant boys. The
      next step was the organisation of workshops on the management of DMD and the
      writing of progress reports on these and other relevant conferences. Getting
      acquainted with the ideas of the protagonists in the research field by holding
      interviews was a decisive prerequisite for this activity. This took place in
      tandem with the development of a new kind of multiplex "family letters" that
      attempted to answer frequently asked questions to many DMD families at the same
      time. When--with the beginning of the new millennium--the endeavours towards gene
      therapies for DMD started to boom all over the scientific world, progress reports
      designed to keep the families informed about research on DMD treatment were added
      to the family letters. These reports that give an account of the latest state of
      the research are written in a plain language that can be understood by
      laypersons. In the meantime the reports have adopted the character of reviews
      that are updated annually. They are written in English and German and translated
      into Spanish and many other languages.

PMID- 20128139
TI  - Sporadic inclusion body myositis: variability in prevalence and phenotype and
      influence of the MHC.
AB  - Sporadic inclusion body myositis (sIBM) is the most common myopathy presenting
      over the age of 40 years but its prevalence varies considerably in different
      populations. Genetic factors play a part in the pathogenesis of sIBM and in
      Caucasians susceptibility has been linked to the HLA-DR3 allele and the 8.1 MHC
      ancestral haplotype (AH) which is also associated with other autoimmune diseases.
      The variable prevalence of sIBM in different populations may be related to
      differences in the population frequency of this haplotype. Our recent
      observations indicate that the clinical phenotype at presentation is also quite
      variable and that the influence of the MHC is more complex than previously
      appreciated with HLA alleles also having modifying effects on the age-at-onset,
      severity and rate of progression of the disease. Recent recombinant mapping
      studies of polymorphisms in the Class II/III regions of the MHC by our group have
      further refined the susceptibility region and have identified a number of
      candidate genes warranting further investigation. The significance of these
      findings for the pathogenesis of the disease is discussed.

PMID- 20128140
TI  - Mild form of Charcot-Marie-Tooth type 1X disease caused by a novel Cys179Gly
      mutation in the GJB1/Cx32 gene.
AB  - Charcot-Marie-Tooth type 1X (CMT1X) disease is inherited as an X-linked dominant
      trait. Female CMT1X patients are usually mildly affected or even asymptomatic
      carriers of mutations in the GJB1 gene coding for a gap junction protein called
      connexin-32 (Cx32). In this report, a five-generation CMT1X family is described
      from which the new mutation in the GJB1 gene Cys179Gly was identified. The
      Cys179Gly mutation is located in the highly conservative domain of the Cx32
      protein. Previous functional studies performed in the oocyte system have shown
      that point mutations in the highly conserved Cx32 cysteine residues result in a
      complete loss of function of the gap junction. However, despite severe
      biochemical defects, the Cys179Gly mutation segregates with a mild CMT1X
      phenotype. This study further documents a discrepancy between biochemical effects
      of GJB1 mutations and the CMT1X phenotype.

PMID- 20128141
TI  - Unusual association of FSHD and extramedullary thoracic tumour in the same
      patient: a case report.
AB  - In the recent literature the association of facioscapulohumeral-dystrophy (FSHD)
      with some hereditary neuromuscular diseases in the same patient has been
      reported. We present the first case in which the genetically confirmed familial
      FSHD is associated with an extramedullary thoracic tumour.

PMID- 20128142
TI  - Fibromyalgia syndrome: case-based learning.

PMID- 20128143
TI  - Fibromyalgia syndrome: diagnosis and comorbidities.

PMID- 20128144
TI  - Advances in the management of fibromyalgia.
AB  - In summary, new FDA approvals offer options for the treatment of FM. CNS targets
      have proven to be effective in the treatment of FM. However, treatment must be
      individualized and the integration of various pharmacologic and nonpharmacologic
      treatments may be the best approach.

PMID- 20128145
TI  - Oxidative stress produced by circulating microparticles in on-pump but not in off
      pump coronary surgery.
AB  - OBJECTIVE: This study was undertaken to assess whether plasmas isolated during
      off-pump coronary surgery trigger less oxidative stress than those isolated
      during on-pump surgery. METHODS AND RESULTS: Plasmas were sampled from patients
      before (TO), just after (TI) and 24 hours after (T2) cardiac surgery (n=24 on
      pump and n=10 off-pump). Rings of rat thoracic aortas were incubated for 20 hours
      with these different plasmas (100 microl + 4 ml medium) or saline (control).
      Thereafter, superoxide anion production was assessed by chemiluminescence and the
      mean signal was expressed as percent of that in the control ring. In rat aorta
      exposed to plasmas from on-pump CABG patients (n=6), the signal was enhanced by
      210 +/- 29% at T1 (P < 0.05) and by 174 +/- 29% at T2 (P < 0.05) versus 53 +/-
      12% at T0. Moreover, at T1 and T2, there was an upregulation of p22(phox), the
      key subunit of NADPH oxidase, the main enzyme involved in oxidative stress of the
      vascular wall. In contrast, off-pump plasmas did not induce this superoxide
      production. Incubation with microparticles obtained by ultracentrifugation also
      markedly enhanced the signal at T1 and T2 (vs. T0) in the on-pump group (but not
      in the off-pump group). Selective removal of CD34, CD105, CD59, CD146, CD42
      microparticles using flow cytometry did not abolish the signal. CRP and SAA
      plasma levels were enhanced only at T2 in both groups. CONCLUSIONS: Plasmas
      isolated after on-pump but not off-pump coronary bypass surgery can induce
      superoxide generation by the vascular wall which seems related to circulating
      microparticles remaining present at least 24 hours after the procedure that might
      be of endothelial origin.

PMID- 20128146
TI  - Impaired chronotropic response to exercise in children with repaired cyanotic
      congenital heart disease.
AB  - OBJECTIVE: Conventionally the heart rate response to exercise has been considered
      as a useful parameter for the assessment of exercise performance. However, in
      patients with surgical repair of congenital heart defects sino-atrial dysfunction
      has been observed after cardiac surgery.The purpose of this study was to assess
      whether the heart rate response to exercise can be used in the assessment of
      exercise performance. METHODS: Fifty-three patients with surgical repair of
      congenital heart disease underwent exercise testing.The patients were 19 children
      with repair of tetralogy of Fallot (TOF), 17 patients with arterial switch
      operation for transposition of the great arteries and 17 patients with a Fontan
      circulation for functional univentricular heart. The patients were compared to
      age-matched control subjects. Exercise capacity was assessed by determination of
      the maximal oxygen uptake.To account for the effect of age and gender on heart
      rate response, values in the patients were compared to age-matched control
      subjects of the same age and gender and were expressed as a Z-score of the normal
      value. RESULTS: In the 3 groups of patients a lower than normal heart rate
      response was observed during submaximal and maximal exercise, varying from -1.7
      to -4.6 standard deviation scores.This was not associated with normal values for
      exercise capacity in patients with TOF or Fontan circulation, as should be
      expected. CONCLUSION: In patients with surgical repair of congenital heart
      disease, the use of heart rate response in the assessment of cardiovascular
      exercise performance may be seriously misleading and should be complemented with
      measurements of gas exchange.

PMID- 20128147
TI  - Ischaemic stroke complicating primary percutaneous coronary intervention in
      patients with ST elevation myocardial infarction.
AB  - OBJECTIVE: We sought to determine the in-hospital incidence and predictors of
      ischaemic stroke in patients with ST elevation myocardial infarction (STEMI)
      undergoing primary percutaneous coronary intervention (PCI). METHODS: We reviewed
      2638 consecutive patients undergoing 2722 pimary PCI procedures for STEMI during
      in-hospital stay. Stroke was defined as any new focal neurological deficit
      lasting > or =24 h, occurring anytime during or after PCI until discharge.
      Patients with haemorrhagic stroke were excluded. Clinical characteristics and in
      hospital outcome were analysed regarding ischaemic stroke in patients undergoing
      primary PCI. RESULTS: Ischaemic stroke was observed in 20 of the 2722 procedures,
      an incidence of 0.73%. Patients with ischaemic stroke were older than patients
      without stroke (mean age 67 +/- 9.6 vs. 56.6 +/- 11.8, P < 0.001). Compared to
      patients without stroke, female gender, diabetes and hypertension were more
      prevalent in patients with stroke. Ischaemic stroke was found to be a powerful
      independent predictor of in-hospital cardiovascular mortality (odds ratio [OR]
      6.32, 1.15-34.7; P < 0.001). Left ventricular ejection fraction (LVEF) < 35% (OR
      3.13, P = 0.04), contrast-induced nephropathy (OR 2.91, P = 0.04) and tirofiban
      use (OR 0.23, P = 0.02) were the independent predictors for in-hospital ischaemic
      stroke. CONCLUSIONS: The present study shows that the incidence of ischaemic
      stroke in patients undergoing PCI for STEMI is higher and ischaemic stroke
      increases in-hospital mortality in these patients. Moreover, LVEF < 35% and
      contrast-induced nephropathy were independent predictors of ischaemic stroke,
      whereas tirofiban use demonstrated a protective effect to this potentially
      catastrophic complication.

PMID- 20128148
TI  - Age-related change of serum angiogenic factor levels in patients with coronary
      artery disease.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and -2
      regulate angiogenesis and might be important in myocardial collateral
      development. Elevated levels of angiogenic growth factors in patients with
      coronary artery disease (CAD) have been reported. However, the age-related change
      of angiogenic growth factors in patients with CAD remains unclear. METHODS AND
      RESULTS: Serum VEGF, Ang-1 and -2 levels were measured by enzyme-linked
      immunosorbent assay kits. Serum VEGF, Ang-1 and -2 levels in patients with CAD
      were significantly higher than those in healthy control subjects. In patients
      aged <61 years and 61 to 70 years, serum Ang-1 and -2 levels were significantly
      higher than in patients aged >70 years, serum Ang-2 levels in patients aged <61
      years were significantly higher than in patients aged from 61 to 70 years. Serum
      VEGF levels were not significantly different in the three age groups. Serum VEGF,
      Ang-1 and -2 levels were not significantly different across the age groups in
      healthy subjects. Regression analysis showed that there was a negative
      correlation between age and Ang-1 and -2 in patients with CAD. CONCLUSION: Serum
      Ang-1 and -2 levels, but notVEGF levels in patients with CAD, are decreased along
      with advancing age.

PMID- 20128149
TI  - Sleep disturbances after cardiac surgery with or without elevated S100B levels.
AB  - OBJECTIVE: The aim of the study was to investigate sleep disturbances of cardiac
      surgery patients with or without elevated S100B levels. METHODS AND RESULTS:
      Twenty-two patients with serum S100B > 0.3 microg/l (study group) 12 hours after
      cardiac surgery with cardiopulmonary bypass and 23 patients with serum S100B <
      0.3 (control group) were investigated in a prospective study. They were evaluated
      with the use of objective sleep tests. Cardiopulmonary bypass has negatively
      affected the sleep characteristics in the postoperative period for both groups.
      Maintenance wakefulness test, total sleep time, total activity score and sleep
      efficiency scores were significantly shorter in the study group in the
      postoperative period. Sleep latency, percentage of wakefulness after sleep onset,
      daytime napping episodes and total nap duration in the same period were
      significantly higher than in the control group. CONCLUSION: Cardiac surgery
      affects a patient's sleep characteristics. Patients with elevated S100B values
      have more sleep disturbances after cardiac surgery than patients with normal
      S100B values.

PMID- 20128150
TI  - Blood pressure and anthropometric measurements in Albanian versus Turkish
      children and adolescents.
AB  - OBJECTIVE: Understanding intercultural, regional and interracial differences in
      blood pressure and anthropometric indices may help to determine the contributors
      of mortality from coronary artery disease in different populations. DESIGN AND
      SETTING: In this article we used data collected from two different countries: (a)
      Survey on school children from Istanbul, Turkey, (b) Cross Sectional Study of
      Albanian school children. RESULTS: We compared age- and gender-matched Albanian
      and Turkish children and adolescents (age 11-12 y and 15-17 y) living in 2
      different countries with regard to blood pressure, weight, height, body mass
      index (BMI), waist circumference, hip circumference, waist-to-hip (WHpR) and
      waist-to-height (WHtR) ratio. We observed significant differences in blood
      pressure, BMI and other anthropometric indices among age- and gender-matched
      subjects from the two countries. Birthweight was lower among Turkish children and
      adolescents compared to Albanian subjects (3258 vs. 3510 g, P < 0.01). Turkish
      children had lower BMI and WHtR compared to Albanian children, while adolescents
      displayed similar BMI and WHtR. Paradoxically, Turkish children and adolescents
      displayed higher systolic blood pressures compared to Albanian children and
      adolescents. Significant differences were observed in the dietary intake and
      physical activity, which may partially explain the differences in blood pressure
      and anthropometric indices. CONCLUSIONS: The socio-economic, dietary and physical
      activity status may account for significant differences in blood pressure and
      anthropometric indices of children and adolescents living in two different
      countries. Future studies should focus on the ethnic differences in the
      definition and prevention of cardiovascular risks among children and adolescents.

PMID- 20128151
TI  - Predictors of atrial arrhythmias in patients with mitral valve prolapse.
AB  - OBJECTIVE: Arrhythmias have been reported to occur frequently in symptomatic
      patients with mitral valve prolapse (MVP). The mechanisms causing atrial
      arrhythmias in patients with MVP have not been fully investigated. The purpose of
      this study was to determine the clinical, echocardiographic and heart rate
      variability parameters, and plasma concentrations of electrolytes and
      inflammatory markers in predicting atrial arrhythmias in patients with MVP.
      METHODS: A total of 58 consecutive patients with MVP were included in this study.
      We performed electrocardiography, echocardiography, Holter analysis, routine
      biochemical tests including plasma concentrations of electrolytes and
      inflammatory markers, and evaluated the clinical characteristics. Atrial
      arrhythmia was defined as occurrence of any of the following: atrial premature
      contractions, atrial couplets, supraventricular tachycardia, atrial flutter or
      fibrillation documented by Holter analysis, continuous monitoring or by
      electrocardiography. RESULTS: Twenty-eight patients (48%) had atrial arrhythmias,
      and 30 (52%) patients had no atrial arrhythmias. Univariable predictors of atrial
      arrhythmias included isovolumetric relaxation time, lateral systolic (S'),
      lateral late diastolic (A'), septal A' Doppler velocities, anterior mitral
      leaflet thickness, anterior mitral leaflet thickness of > or =5 mm, posterior
      mitral leaflet thickness and the occurrence of moderate to severe mitral
      regurgitation. Multivariable logistic regression analysis showed that occurrence
      of moderate to severe mitral regurgitation was the only independent predictor of
      atrial arrhythmias (relative risk: 2.4, 95% confidence interval 1.32-4.86, P =
      0.005). CONCLUSIONS: The present study showed that the only independent predictor
      of atrial arrhythmias in patients with MVP is the occurrence of moderate to
      severe mitral regurgitation.

PMID- 20128152
TI  - Impact of the lesion location on fractional flow reserve.
AB  - INTRODUCTION: Fractional flow reserve (FFR) is a method to determine the
      significance of a lesion. Although an FFR measurement of < 0.75 is accepted to
      show ischaemia, the effect of the location of the lesion on the coronary artery
      is not known. This study investigates the effect of lesion location on the FFR
      measurement. METHOD: Ninety-nine eligible patients who had undergone FFR
      measurement of an intermediate lesion (40-70% stenosis) at the left anterior
      descending coronary artery (LAD) were included. The lesions proximal to the
      origin of the first diagonal branch were accepted as proximal lesions and the
      remaining lesions were accepted as distal.The patients were categorized according
      to the degree of the percent diameter stenosis (40-50%, 50-60%, and > 60%) and
      the reference vessel diameter (RVD) (> or = 2.8 mm and < 2.8 mm). We compared the
      FFR measurements between proximal and distal lesions among different categories
      which were set according to anatomical features of the lesions. RESULTS: No
      significant difference was found between the FFR values of proximal and distal
      lesions with a similar percent diameter stenosis (0.86 +/- 0.08 vs. 0.83 +/-
      0.08; 0.77 +/- 0.11 vs. 0.80 +/- 0.09; 0.75 +/- 0.07 vs. 0.77 +/- 0.08; P =
      0.646).We did not find a difference between the FFR values of proximal and distal
      lesions with a similar RVD either (0.78 +/- 0.03 vs. 0.81 +/- 0.02; 0.84 +/- 0.03
      vs. 0.81 +/- 0.01; P = 0.976). Major adverse cardiac event incidence was also
      similar for proximal and distal lesions (23% vs. 20%; P = 0.793). CONCLUSION:
      Fractional flow reserve can show the physiological significance of a stenosis
      independent of the anatomical location of the lesion on the coronary artery.

PMID- 20128153
TI  - Results of radiofrequency ablation for permanent atrial fibrillation in patients
      undergoing mitral valve surgery.
AB  - OBJECTIVES: The study aim was to evaluate the safety and feasibility of
      radiofrequency ablation for the surgical treatment of permanent atrial
      fibrillation in patients with degenerative mitral valve disease. DESIGN: From
      August 2000 to August 2003, 40 consecutive patients (mean age 69.0 +/- 9.3 years)
      with permanent atrial fibrillation and degenerative mitral valve disease
      underwent surgical radiofrequency ablation in conjunction with 22 mitral valve
      repairs and 18 mitral valve replacements. The mean duration of chronic AF was 5.1
      +/- 3.4 years. The completeness of follow-up was 100%. The mean follow-up time
      was 4.6 +/- 2.0 years (range 0 to 7.8 years). RESULTS: Thirty-day mortality was
      2.5% (1 patient), the cause of death was cardiac failure. Cardiac failure and
      temporary A-V block were the most common postoperative complications. Both
      occurred in 10% (4 patients). No complication was related to the ablation
      procedure. At discharge, 65% (26/40) of the patients were in sinus rhythm.
      Overall incidence of sinus rhythm at the end of the follow-up was 56.4%
      (22/39).The 1-, 3- and 5-year survival was 97.5%, 91.8% and 85.9%, respectively.
      CONCLUSION: Mitral valve surgery combined with radiofrequency ablation is a safe
      and effective procedure in patients with permanent atrial fibrillation and
      degenerative mitral valve disease. The result is encouraging in restoring sinus
      rhythm, and an excellent postoperative survival rate can be achieved.

PMID- 20128154
TI  - Prevalence of cardiovascular risk factors in an unselected italian population.
      Results of the Cardiolab Project 2004-2008.
AB  - OBJECTIVE: Screening and educational campaigns on cardiovascular (CV) risk
      factors are important for primary and secondary prevention of CV disease. The
      CardioLab project is an observational cross-sectional study aimed at determining
      the prevalence of CV risk factors in a large unselected sample of the Italian
      population leaving in northern, central and southern Italy. METHODS AND RESULTS:
      Data collection included family and clinical history, anthropometric data, blood
      pressure, blood glucose and total cholesterol values. Individual CV risk profile
      was assessed throughout by the risk charts of both the Progetto Cuore and the
      Score Project. In 36,161 participants (56.3% men) with a mean age of 60 years a
      complete assessment of the above mentioned variables was obtained. 44.4% of the
      screened subjects was overweight, while approximately 20% of the population
      displayed an obese state with a body mass index >30 kg/m2. Alterations in blood
      glucose levels indicating the presence of glucose intolerance were identified in
      11.5% of the population while 9.3% displayed overt diabetes. 36.1% and 42.3% had
      elevated total cholesterol levels (> 200 mg/dl) and blood pressure values (> or =
      140/90 mmHg), respectively. New diagnosis of diabetes, hypercholesterolaemia and
      hypertension was obtained in 5.3%, 23.6% and 19.6%, respectively. Global
      assessment of the CV risk showed that approximately 12.6% of the population is at
      a high risk of CV events over a 10-year period. CONCLUSIONS: This large-scale
      observational study provides important information on the CV risk profile of an
      unselected Italian population and underlines the need for a more aggressive
      identification and appropriate correction of CV risk factors.

PMID- 20128155
TI  - In rats with myocardial infarction, interference by simvastatin with the TLR4
      signal pathway attenuates ventricular remodelling.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of
      simvastatin on TLR4,TNF-alpha and IL-6 expression in the myocardium and its
      relation to left ventricular (LV) remodelling in a rat model of myocardial
      infarction (MI) and to investigate the mechanism by which simvastatin improves LV
      remodelling in rats after MI. METHODS AND RESULTS: The rat MI models were
      established by ligation of the left anterior descending coronary artery and
      divided into three groups: (I) an untreated MI group; (2) a group treated with
      simvastatin [40 mg/(kg/d)] for 4 weeks; (3) the sham group. Cardiac geometry and
      function were determined by echocardiography and infarct size was determined by
      the histomorphometric analysis; the expression ofTLR4 in the myocardium was
      measured by RT-PCR and western blotting;TNF-alpha and IL-6 levels in myocardial
      homogenate and serum were measured by ELISA. LVEDD and LVESD significantly
      increased and fractional shortening (FS) markedly decreased in the MI group. It
      was clear that simvastatin inhibited LV dilation and improved LV function after
      MI without affecting infarct size. The expression of TLR4, TNF-alpha and IL-6 in
      the myocardium significantly increased in the MI group and simvastatin markedly
      inhibits the expression of TLR4, TNF-alpha, and IL-6 in the myocardium after MI.
      Serum TNF-alpha and IL-6 levels between the MI group and the simvastatin group
      remained unchanged. Both in the MI group and the simvastatin group,TLR4 protein
      positively related to LVEDD and to the levels of TNF-alpha and IL-6 in the
      myocardium, respectively. CONCLUSION: Amelioration of LV remodelling in rats
      after MI by simvastatin might be associated with its effect on the TLR4-mediated
      signalling pathway in the myocardium.

PMID- 20128156
TI  - Assessment of left ventricular function in non-dilated and dilated hearts:
      comparison of contrast-enhanced 2-dimensional echocardiography with multi
      detector row CT angiography.
AB  - OBJECTIVE: Multidetector-row CT (MDCT) and contrast-enhanced echocardiography
      (CEE) are being increasingly used for assessment of left ventricular (LV)
      function. Excellent spatial and contrast resolution of MDCT allows this
      evaluation along with coronary angiography. CEE improves the accuracy of 2D
      echocardiography. Data on side-by-side comparison of both techniques for
      assessment of LV size and function in subjects with a non-dilated or dilated left
      ventricle are limited. METHODS AND RESULTS: Our study population included 64
      patients. Group I included 31 patients with an implanted pacemaker who had a non
      dilated left ventricle with preserved systolic function. Group II comprised 33
      patients with dilated cardiomyopathy and severe systolic LV dysfunction. LV end
      diastolic and end-systolic volumes (LVEDV, LVESV) and ejection fraction (LVEF)
      were assessed using both CEE and short-axis MDCT. The results obtained by both
      techniques were compared by linear regression and Bland-Altman analysis.
      Additionally, intra- and interobserver reproducibility was assessed. Both CEE and
      MDCT measurements highly correlated (r = 0.61-0.94). However, CEE significantly
      underestimated LVEDV and LVESV, and this bias was higher with enlarged LV
      volumes. LVEF was overestimated by CEE in both groups with a higher bias in the
      group with preserved systolic function. Both intra- and interobserver
      reproducibility was significantly better for MDCT, the worst reproducibility was
      observed for CEE in group I. CONCLUSION: Despite a high correlation between MDCT
      and CEE measurements, CEE provides consistently lower volumes and higher LVEF.
      This suggests that both methods are not completely interchangeable.
      Reproducibility of CEE is inferior to reproducibility of MDCT, especially in non
      dilated left ventricles with preserved function.

PMID- 20128157
TI  - The Brugada syndrome.
AB  - The Brugada syndrome is an inherited cardiac disorder initially described in 1992
      by Pedro and Josep Brugada, with variable electrocardiographic features
      characteristic of right bundle-branch block, persistent ST-segment elevation in
      the precordial leads (VI-V3) at rest and sudden cardiac death. The genetic
      abnormalities that cause Brugada syndrome have been linked to mutations in the
      ion channel gene SCN5A which encodes for the alpha-subunit of the cardiac sodium
      channel. A consensus conference report published in 2002 described the diagnostic
      criteria for the Brugada syndrome and described the three distinct types of
      Brugada syndrome. In 2005, a second consensus report was published which
      described the risk stratification and approaches to therapy. Two specific types
      of ST-segment elevation, coved and saddleback, are observed in the Brugada
      syndrome, the former of which is reported to relate to a higher incidence of
      ventricular tachycardial ventricular fibrillation (VTNF) and sudden cardiac
      death.The objective of this paper is to review the genetics and the molecular
      biology behind the Brugada syndrome, the diagnostic criteria, including clinical
      and electrocardiographic characteristics, and current management.

PMID- 20128158
TI  - A giant thromboembolus captive in a patent foramen ovale.

PMID- 20128159
TI  - "Textbook" myxoma.

PMID- 20128160
TI  - An alien in the heart: giant infective endocarditis.

PMID- 20128161
TI  - Recurrent left ventricular myxoma presenting as cerebrovascular accidents in a
      teenage girl.
AB  - Myxoma cordis is the most frequent primary cardiac tumour in adults. Paediatric
      primary cardiac tumours are rare, the most common type being rhabdomyoma. Atrial
      and ventricular myxomas occur infrequently in the paediatric age group.
      Intracardiac myxomas are seen with an estimated incidence of 0.5 per million
      population per year. Approximately 70% of the affected patients are of female
      gender. Recurrences are rare (1.3%). Asymptomatic recurrences are observed in
      young patients who have a familial history of tumour or multifocal myxomas.
      Although rare, cardiac aetiology (atrial fibrillation, intracardiac thrombi,
      patent foramen ovale, myxoma, endocarditis) should be considered. In children
      presenting with central neurological symptoms, a cardiac aetiology has to be
      considered. We describe a rare case of an 18-year-old girl presenting with a
      recurrent left ventricular myxoma, accompanied by neurological deficits.

PMID- 20128162
TI  - Endocarditis and giant mitral valve aneurysms.
AB  - In a 65-year-old man with infective endocarditis, multiple mitral valve aneurysms
      were detected by echocardiography. Surgical treatment was successful. Aneurysms
      of the valve are a relatively rare complication of infective endocarditis. Prompt
      diagnosis and treatment can prevent complications such as embolisation and
      rupture of the aneurysms. For a patient with a history of unknown fever, this
      point should be kept in mind.

PMID- 20128163
TI  - Changing the guiding catheter over the coronary wire: a simple (and cheap)
      technique to get out of trouble.
AB  - During acute myocardial infarction (MI), the culprit lesion is usually composed
      of thrombus and soft plaque. Sometimes, calcification can be present. A patient
      with acute MI, due to sub-occlusion of the ostial right coronary artery,
      underwent primary percutaneous intervention. The procedure was complicated by
      severe dissection after balloon inflation. The use of standard materials did not
      allow stent passage, due to an underestimated severe calcification. To provide
      better support, we changed the guiding catheter for a more supportive one over
      the coronary guidewire, left in place to avoid rewiring the false lumen.This
      technique allowed successful stent deployment.

PMID- 20128164
TI  - Light chain deposition disease as a rare cause of restrictive cardiomyopathy.
AB  - We report an unusual case of a 47-year-old Caucasian woman who presented with
      severe dyspnoea as a manifestation of restrictive cardiomyopathy, found to be due
      to myocardial deposition of kappa light chains. Non-routine specific
      immunofluorescence stainings of endomyocardial biopsy specimens were key for the
      diagnosis of myocardial light chain deposition disease. We discuss non
      amyloidotic cardiac immunoglobulin deposition disease in contrast to cardiac
      amyloidosis.

PMID- 20128165
TI  - Severe ostial stenosis of the left coronary artery in a 12-year-old girl as the
      first manifestation of Takayasu's arteritis.
AB  - We report the case of a 12-year-old girl who presented with isolated chest pain
      on minimal exertion over the last 2 months. A coronary angiography revealed
      severe narrowing of the left coronary artery ostium and increased thickness of
      the ascending aortic wall was demonstrated by transoesophageal echocardiography,
      suggesting the diagnosis ofTakayasu's arteritis. The patient was successfully
      treated with corticosteroids and coronary artery bypass graft surgery.

PMID- 20128166
TI  - Very late drug-eluting stent thrombosis in the perioperative period of endoscopic
      choledocholithotomy.
AB  - Very late stent thrombosis is an uncommon but life-threatening complication after
      drug-eluting stent implantation in patients with coronary artery disease.
      Discontinuation of antiplatelet therapy is reported to be the most powerful
      predictor of stent thrombosis. This article reports on a case of very late stent
      thrombosis 54 months after implantation of a drug-eluting stent, in a patient who
      discontinued dual antiplatelet therapy only 11 days before endoscopic
      choledocholithotomy, and argues in favour of continuing aspirin therapy
      perioperatively in surgical patients with low bleeding risk, even if dual
      antiplatelet therapy has been followed more than 12 months after stent
      implantation.

PMID- 20128167
TI  - Sudden cardiac arrest in a patient with an anomalous left main coronary artery
      originating from the pulmonary artery.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is an uncommon cardiac abnormality. The clinical picture of ALCAPA may range from
      asymptomatic course with normal life span to sudden cardiac death. Moreover, from
      the standpoint of resuscitation science, it constitutes a disadvantageous anatomy
      for coronary perfusion pressure, generated by chest compressions, which is
      critical for the return of spontaneous circulation. Here, we report an ALCAPA
      case diagnosed after out-of-hospital cardiac arrest and successful
      cardiopulmonary resuscitation.

PMID- 20128168
TI  - Gastroenteritis with severe consequences: a case of sotalol-induced torsades de
      pointes.
AB  - We present a case of sotalol-induced prolongation of the QT-interval with
      torsades de pointes in an octogenarian who was hospitalized because of
      gastroenteritis causing prerenal acute renal failure. Subsequent accumulation of
      sotalol caused a severe prolongation of the QT-interval on the surface ECG and
      ultimately torsades de pointes with loss of consciousness. The patient was
      successfully treated with temporary cardiac pacing, intravenous magnesium sulfate
      and definitive withdrawal of sotalol. The electrophysiological basis of the pro
      arrhythmic properties of sotalol is reviewed in brief, additional risk factors
      are identified and treatment is outlined.

PMID- 20128169
TI  - Role of the renin-angiotensin system in the promotion of atrial fibrillation.

PMID- 20128170
TI  - Change is in the air.

PMID- 20128171
TI  - SDSMA and health system reform.

PMID- 20128172
TI  - Osteodystrophy in celiac disease: ultimate complications and possible treatment.
AB  - Hypovitaminosis D and its consequences are significant complications in the
      course of untreated celiac disease (CD). We report a case that illustrates the
      natural evolution of osteomalacia in an adult patient with untreated CD and his
      response to vitamin D supplementation. In patients with complicated CD and
      hypovitaminosis D, vitamin D-2 replacement in high enough doses is important to
      improving functional performance and for the treatment of osteomalacia.

PMID- 20128173
TI  - Propoxyphene and pain management in the elderly.
AB  - Pain is frequently reported and often undertreated in the elderly population. In
      light of these concerns, it is important to examine potentially ineffective or
      problematic pain medications. Propoxyphene is one such agent whose efficacy and
      safety have been questioned by researchers, clinicians and the U.S. Food and Drug
      Administration (FDA). Specifically, multiple studies have found propoxyphene to
      be no more effective than acetaminophen (APAP), yet propoxyphene causes opioid
      side effects and has been involved in many drug-related deaths. In addition,
      propoxyphene/APAP products are often prescribed at doses that exceed maximum
      values (49.2 percent of APAP/propoxyphene napsylate 100 prescriptions for South
      Dakota Medicaid patients exceeded the maximum daily dose). The relevance of
      propoxyphene use is seen by the 7.1 percent prevalence of propoxyphene
      prescriptions among the South Dakota Medicare beneficiaries, which is comparable
      to the 6.8 percent reported in the U.S. community-based Medicare population.
      Therefore, it is very important to consider alternatives to propoxyphene such as
      APAP, nonsteroidal anti-inflammatory drugs (rare use due to adverse effects) and
      other opioids, when managing elderly patients with pain.

PMID- 20128174
TI  - Save green, go generic: be prepared to answer the $4 question.

PMID- 20128175
TI  - The tao of medicine: four pillars for "the way" ahead--part 1.

PMID- 20128176
TI  - H1N1 clinicians questions and answers. CDC recommendations for the 2009 H1N1
      vaccine.

PMID- 20128177
TI  - Held hostage by the GPCI.

PMID- 20128178
TI  - The corn-skin connection.

PMID- 20128179
TI  - Voice production mechanisms following phonosurgical treatment of early glottic
      cancer.
AB  - OBJECTIVES: Although near-normal conversational voices can be achieved with the
      phonosurgical management of early glottic cancer, there are still acoustic and
      aerodynamic deficits in vocal function that must be better understood to help
      further optimize phonosurgical interventions. Stroboscopic assessment is
      inadequate for this purpose. METHODS: A newly developed color high-speed
      videoendoscopy (HSV) system that included time-synchronized recordings of the
      acoustic signal was used to perform a detailed examination of voice production
      mechanisms in 14 subjects. Digital image processing techniques were used to
      quantify glottal phonatory function and to delineate relationships between vocal
      fold vibratory properties and acoustic perturbation measures. RESULTS: The
      results for multiple measurements of vibratory asymmetry showed that 31% to 62%
      of subjects displayed higher-than-normal average values, whereas the mean values
      for glottal closure duration (open quotient) and periodicity of vibration fell
      within normal limits. The average HSV-based measures did not correlate
      significantly with the acoustic perturbation measures, but moderate correlations
      were exhibited between the acoustic measures and the SDs of the HSV-based
      parameters. CONCLUSIONS: The use of simultaneous, time-synchronized HSV and
      acoustic recordings can provide new insights into postoperative voice production
      mechanisms that cannot be obtained with stroboscopic assessment.

PMID- 20128180
TI  - Supracricoid partial laryngectomy: swallowing, voice, and speech outcomes.
AB  - OBJECTIVES: The purpose of the study was to describe the swallowing and vocal
      function of patients after supracricoid partial laryngectomy (SCPL) as they
      changed over the first postoperative year. METHODS: Ten patients with laryngeal
      carcinoma underwent SCPL at Johns Hopkins Hospital between August 2003 and May
      2005. Clinical and videofluoroscopic swallowing examinations and perceptual,
      acoustic, aerodynamic, and video-stroboscopic voice evaluations were completed
      before operation and at 3 weeks (swallowing only) and 2 (voice only), 6, and 12
      months after operation. RESULTS: The mean time to gastrostomy tube removal was 82
      days. The patients tolerated an increased variety of foods over the first
      postoperative year. All patients initially used therapeutic strategies to swallow
      safely, and some still required them at 1 postoperative year. Over the year, the
      perceptual ratings of voice quality improved significantly. There were no
      consistent changes in acoustic or aerodynamic measures. The number of patients
      who used multiple vibratory sources to phonate increased over the year.
      CONCLUSIONS: The patients tolerated regular diets, yet continued to exhibit
      silent aspiration and a variety of decompensations. Their voices were breathy,
      rough, and strained. Their voice quality ratings improved over the year. Group
      changes were not captured, and it appears that the changes in speech and voice 2
      months after surgery were subtle.

PMID- 20128181
TI  - Level of complete dissection of the ethmoid sinuses with a computed tomographic
      image guidance system.
AB  - OBJECTIVES: We sought to determine the adequacy of endoscopic total ethmoidectomy
      with the use of a computed tomographic (CT) image guidance system. METHODS:
      Endoscopic ethmoid sinus dissections were performed on cadavers by
      otolaryngologists. All cadavers were scanned before dissection. On each side of
      the cadaver, the ethmoid sinuses were examined independently. A complete
      endoscopic ethmoidectomy was performed with a CT image guidance system. After the
      endoscopic ethmoidectomy, the cadaver underwent a postdissection CT scan. The
      postdissection CT images were then evaluated for the level of complete dissection
      of the anterior and posterior ethmoid sinuses. RESULTS: There were 18 ethmoid
      sinuses in the study. One specimen underwent a complete total ethmoidectomy with
      no residual cells. There were 4 complete anterior ethmoidectomies and 5 complete
      posterior ethmoidectomies. Overall, the average numbers of residual anterior
      ethmoid and posterior ethmoid air cells were 1.39 and 1.22, respectively. This
      difference was not statistically significant. The skull base was dissected more
      completely than the lamina papyracea, with a significant difference (p = 0.03).
      There was no difference in terms of residual cells between the left and right
      ethmoid sinuses (p > 0.05). CONCLUSIONS: Even with the use of a CT image guidance
      system, a complete ethmoidectomy was still difficult to achieve. Residual ethmoid
      sinus cells were more commonly found along the lamina papyracea than along the
      skull base.

PMID- 20128182
TI  - Relationship between squamous cell carcinoma antigen and the clinical severity of
      allergic rhinitis caused by Dermatophagoides farinae and Japanese cedar pollen.
AB  - OBJECTIVES: Allergic rhinitis is known to be related to the Th2-type immune
      response, but no sensitive biomarker of severity yet exists. Serum squamous cell
      carcinoma antigen (SCCA) is clinically used as a popular tumor biomarker. We have
      demonstrated that SCCA is related to allergic diseases such as asthma. The
      purpose of the present study was to clarify the relationship between allergic
      rhinitis and SCCA, which had not yet been investigated. METHODS: We compared the
      serum SCCA levels in patients with allergic rhinitis due to Japanese cedar pollen
      and Dermatophagoides farinae with those in normal subjects. Thereafter, the
      correlations between the clinical severity of allergic rhinitis and the serum
      levels of SCCA were investigated. Furthermore, the influence of 8 variables
      (serum levels of SCCA, immunoglobulin E, eosinophil cationic protein, and
      eosinophils; age; gender; oral administration of antiallergic or antihistaminic
      agents; and use of nasal drops) in regard to the severity of allergic rhinitis
      was studied by a multiple regression analysis. RESULTS: The SCCA levels of the D
      farinae group were statistically higher than those of the control group, and they
      correlated with the severity of rhinitis. Among the 8 variables, only the SCCA
      level was found to be a predictive factor of severity on a multiple regression
      analysis. No relationship between SCCA level and Japanese cedar pollen allergy
      was demonstrated. CONCLUSIONS: These results suggest that the serum SCCA level
      may be a useful biomarker to evaluate the severity of allergic rhinitis caused by
      D farinae.

PMID- 20128183
TI  - Negrevergne otoplasty technique.
AB  - OBJECTIVES: More than 200 different otoplasty procedures have been described in
      the literature to treat patients with prominent ears. However, no simple "best"
      technique exists. METHODS: The Negrevergne otoplasty technique was developed by
      Michel Negrevergne and adopted in the Georges Portmann Institute in France. The
      technique includes partial-thickness posterior scoring of the auricular cartilage
      by use of monopolar cutting diathermy. RESULTS: A telephone survey was designed
      solely for this study, aimed to give general information about the technique's
      outcomes. The survey, conducted by the first author among his patients who were
      followed up for more than 1 year, revealed that most patients (46 of 52) were
      very to completely satisfied with the appearance and symmetry of their ears.
      Furthermore, evaluation according to the Global Aesthetic Improvement Scale was
      performed by a blinded nonparticipating observer using the medical photographs of
      48 patients who consented to "medical photography" to evaluate the effect of
      treatment. All patients were rated as "improved" or better on the Global
      Aesthetic Improvement Scale at 52 weeks. There were no ratings of "no change" or
      "worse." CONCLUSIONS: The Negrevergne otoplasty technique is a relatively simple
      and rapid procedure that maintains the natural contours of the auricle with
      little morbidity by addressing the poorly developed or absent antihelical fold,
      an abnormally large concha, and a prominent lobule.

PMID- 20128184
TI  - Functional results of Reinke's edema surgery using a microdebrider.
AB  - OBJECTIVES: We evaluated the functional results of Reinke's edema surgery using a
      microdebrider. METHODS: In this prospective nonrandomized study from 2004 through
      2008, functional surgery using a microdebrider was performed on patients with
      severe Reinke's edema. Comparisons were conducted for preoperative and
      postoperative phonatory function using both subjective grade (G), roughness (R),
      breathiness (B), asthenia (A), and strain (S) scoring and objective Multi
      Dimensional Voice Program parameters. Statistical analysis was done by paired t
      test, and a p value of less than 0.05 was considered significant. RESULTS:
      Seventeen patients were enrolled in this study, with a median age of 56 years and
      a median observation period of 129 days. The male-to-female ratio was 1 to 2.4.
      No major complications were observed in the perioperative period. Significant
      improvement was observed in the subjective values of G, R, B, and S. Improvement
      was also observed in the fundamental frequency, pitch perturbation quotient, and
      amplitude perturbation quotient calculated by the Multi-Dimensional Voice
      Program. CONCLUSIONS: The microdebrider is a useful tool in functional surgery
      for severe Reinke's edema and gives good functional outcomes. Surgeons can
      swiftly complete the key steps of removing pathological submucosal tissue and
      preserving the normal epithelium with an excellent surgical view.

PMID- 20128185
TI  - Improved tracheoesophageal prosthesis sizing in office-based tracheoesophageal
      puncture.
AB  - OBJECTIVES: Tracheoesophageal puncture (TEP) for postlaryngectomy speech is
      increasingly being performed as an office-based procedure. We review our
      experience with office-based TEP and compare outcomes with those of operating
      room-based TEP. Our hypothesis was that office-based TEP results in improved
      prosthesis sizing, reducing the number of visits dedicated to prosthesis
      resizing. METHODS: A retrospective chart review was performed of all patients who
      underwent secondary TEP at our institution from 2001 to 2008. The primary
      dependent measure was the change in the length of the voice prosthesis. We also
      evaluated the number of visits made to the speech-language pathologist for
      resizing before a stable prosthesis length was achieved, and the number of days
      between voice prosthesis placement and the date a stable prosthesis length was
      observed. RESULTS: Thirty-one patients were included in this study. There was a
      significant difference in prosthesis length change between patients who had
      office-based TEP and patients who had operating room-based TEP (p < 0.001). In
      addition, the office-based cohort required fewer visits to the speech-language
      pathologist for TEP adjustments before a stable TEP length was achieved (p <
      0.001). CONCLUSIONS: Voice prosthesis sizing was better in patients who had
      office-based TEP than in patients who had operating room-based TEP. This outcome
      is likely due to the lesser degree of swelling of the tracheoesophageal party
      wall in the office-based procedure.

PMID- 20128186
TI  - Subarcuate supralabyrinthine approach for supralabyrinthine petrosal
      cholesteatoma.
AB  - Congenital cholesteatomas of the petrosal apex account for 1% to 3% of all
      cholesteatomas and often present an important surgical challenge. This report
      describes an exceptional case of a "nondestructive" translabyrinthine surgical
      approach to a large congenital petrosal cholesteatoma that threatened the
      vestibulum, superior semicircular canal, facial nerve, and internal auditory
      canal. We applied a nonconventional transmastoid subarcuate supralabyrinthine
      approach in a 20-year-old patient by accessing the lesion through the center of
      the superior semicircular arch without damaging the integrity of the canal. This
      led to a complete removal of the petrosal cholesteatoma with preservation of
      hearing and vestibular function. Follow-up imaging performed 1 and 2 years after
      operation by means of non-echo-planar diffusion-weighted imaging did not show
      residual cholesteatoma. This report describes the first successful use of a
      subarcuate supralabyrinthine approach through the arches of the superior
      semicircular canal in a case of petrosal cholesteatoma.

PMID- 20128187
TI  - Congenital bilateral vocal fold paralysis and Charcot-Marie-Tooth disease.
AB  - We present the case of a patient with Charcot-Marie-Tooth disease (CMT) type 1
      with congenital bilateral vocal fold paralysis in order to emphasize the
      treatment options and long-term outcome. The case is reviewed with regard to
      presentation, differential diagnosis, and treatment. We also reviewed the
      literature to determine the frequency of congenital and childhood presentations
      of bilateral vocal fold paralysis associated with CMT, most specifically CMT type
      1. We found only 14 children reported to have bilateral vocal fold paralysis
      associated with CMT, and only 1 of these cases was associated with CMT type 1.
      None of these patients had congenital vocal fold paralysis. Because of the
      degenerative nature of the disease, our patient underwent endoscopic cordotomy to
      avoid tracheotomy. We conclude that CMT should be included in the differential
      diagnosis in evaluating neonates with bilateral vocal fold paralysis. If CMT is
      definitively diagnosed, it could alter the course of treatment.

PMID- 20128188
TI  - Effects of Gold laser on the avian chorioallantoic membrane.
AB  - OBJECTIVES: Office-based lasers have revolutionized the treatment of laryngeal
      disease. The 980-nm Gold laser is a device that may offer some practical
      advantages over other office lasers. The chick chorioallantoic membrane has been
      proposed as a model for predicting the effects of photoangiolytic lasers on vocal
      fold microvasculature. We sought to evaluate the effects of the Gold laser in
      this model. METHODS: Vascular reactions in first-order vessels were determined
      for the Gold laser with both 0 degree straight and 30 degrees angled laser
      fibers. Vessels were treated at 15 W and a 500-ms pulse interval, with a 1-mm
      working distance. Pulse widths of 300 ms and 500 ms were evaluated. All vessels
      were treated until selective coagulation or vessel rupture. RESULTS: We performed
      60 trials on 30 embryos. The mean energy delivered was 33.7 J for the straight
      fiber and 51.2 J for the angled fiber. The laser achieved selective vessel
      coagulation without rupture in 100% (30 of 30) of straight fiber trials and in
      100% (30 of 30) of angled fiber trials. In 6.7% (2 of 30) of straight fiber and
      10% (3 of 30) of angled fiber trials, it caused minor injury to the surrounding
      albumin as indicated by white coagulum outside the vessel. CONCLUSIONS: The Gold
      laser effectively coagulates small vessels without rupture at a working distance
      of 1 mm and settings of 15 W, 500-ms pulse interval, and 300- to 500-ms pulse
      width.

PMID- 20128189
TI  - Spontaneous and evoked laryngeal electromyography of the thyroarytenoid muscles:
      a canine model for intraoperative recurrent laryngeal nerve monitoring.
AB  - OBJECTIVES: We sought to determine the feasibility of performing spontaneous and
      evoked intraoperative laryngeal electromyography (L-EMG) using nerve monitoring
      equipment and to compare recording electrode configurations and methods of
      recurrent laryngeal nerve (RLN) stimulation in dogs. METHODS: Four beagles
      underwent crush injury of the left RLN, and 2 beagles underwent left RLN
      transection. Serial spontaneous and evoked L-EMG was recorded with the NIM
      Response nerve monitoring system under sedation. Transesophageal, percutaneous,
      and direct open RLN stimulation was performed. Recordings of spontaneous and
      evoked responses were made with endotracheal tube surface electrodes and bipolar
      vocal fold needle electrodes. The L-EMG procedures were repeated every 1 to 2
      weeks after injury, and intersubject and intertrial differences were evaluated.
      RESULTS: Low-amplitude motor unit action potentials, polyphasic potentials,
      fasciculations, and fibrillations were detected in injured animals with bipolar
      needle recording electrodes with this system of spontaneous L-EMG. The surface
      recording electrodes did not detect pathologic waveforms. Percutaneous needle
      stimulation of the RLN is possible at currents slightly higher than those used
      for direct stimulation. Consistent, discrete, transesophageal stimulation of the
      RLN could not be reliably performed. Recording evoked responses with needle
      electrodes generated sharper waveforms, facilitating calculation of latency and
      wave duration. Evoked L-EMG utilizing surface recording electrodes limited the
      intertrial and intersubject variability of evoked amplitude. CONCLUSIONS: Typical
      patterns of nerve injury can be detected with this system of intraoperative L-EMG
      in a canine model. Quantitative measures of amplitude, latency, and wave duration
      in healthy and injured canine RLNs may be determined with this system.

PMID- 20128190
TI  - Cod liver oil, the ratio of vitamins A and D, frequent respiratory tract
      infections, and vitamin D deficiency in young children in the United States.

PMID- 20128191
TI  - A shift in paradigm.

PMID- 20128192
TI  - 2009 JCO Orthodontic Practice Study. Part 1 Trends.

PMID- 20128193
TI  - Biomechanics and the paradigm shift in orthodontic treatment plannin.

PMID- 20128194
TI  - Clinical implications of the University of Washington post-retention studies.

PMID- 20128195
TI  - A new approach to indirect bonding.

PMID- 20128196
TI  - A maxillary expander for treatment of unilateral posterior crossbite with
      anterior open bite.

PMID- 20128197
TI  - Modification of a cheek retractor for high-volume evacuation.

PMID- 20128198
TI  - Retail healthcare recipe: will too many ingredients spoil the sauce?

PMID- 20128199
TI  - Actinic keratosis: treat lesions to reduce cancer risk.

PMID- 20128200
TI  - Your financial vital signs: start the new year with a checkup.

PMID- 20128201
TI  - 2009 national salary & workplace survey: good news in troubled economy.

PMID- 20128202
TI  - From terminal disease to chronic illness: HIV infection in 2010.

PMID- 20128203
TI  - Treating sinusitis in adults.

PMID- 20128204
TI  - Bacterial vaginosis: update on evidence-based care.

PMID- 20128205
TI  - Diabetes care for Hispanic patients: honoring culture while promoting glycemic
      control.

PMID- 20128206
TI  - Life changes: lessons from a late bloomer.

PMID- 20128207
TI  - Clinician in the classroom: from seasoned professional to novice.

PMID- 20128208
TI  - Strengthening our health care workforce.

PMID- 20128209
TI  - Falls and fall risks in the elderly: a population at risk.

PMID- 20128210
TI  - Health Information Security & Privacy Collaboration (HISPC) Provider Education
      Toolkit (PET).

PMID- 20128212
TI  - Negating "climategate".

PMID- 20128211
TI  - Poisoned shipments.

PMID- 20128213
TI  - Mouse mash-up.

PMID- 20128214
TI  - Lost giants.

PMID- 20128216
TI  - Bigger, better broadband.

PMID- 20128215
TI  - Naked gaming.

PMID- 20128217
TI  - Comparatively easy.

PMID- 20128218
TI  - Fixing the broken policy process.

PMID- 20128219
TI  - Cultivate your garden.

PMID- 20128220
TI  - The real promise of synthetic biology.

PMID- 20128221
TI  - Cloudy with a chance of stars. Making a star is no easy thing.

PMID- 20128222
TI  - The naked truth.

PMID- 20128223
TI  - Better mileage now.

PMID- 20128224
TI  - The art of bacterial warfare.

PMID- 20128225
TI  - Fixing the global nitrogen problem.

PMID- 20128226
TI  - Seeing forbidden colors.

PMID- 20128227
TI  - The prolific afterlife of whales.

PMID- 20128228
TI  - Can people ever lose their fingerprints?

PMID- 20128229
TI  - Sublingual immunotherapy: certainties, unmet needs and future directions.

PMID- 20128230
TI  - Pre-lethal anaphylaxis to carboxymethylcellulose confirmed by identification of
      specific IgE--review of the literature.
AB  - BACKGROUND: Carboxymethylcellulose (CMC) is used extensively in the
      pharmaceutical and food industries on account of its various properties.
      Anaphylactic reactions are rare. It has been reported principally after intra
      articular infiltration of sustained-release corticosteroids containing CMC and,
      very rarely, after barium enema. METHODS: A case of pre-lethal anaphylactic shock
      after barium enema was studied by prick-test, intra-dermal reaction (IDR),
      leukocyte histamine release test (LHRT), basophil activation test (BAT), cystein
      leukotriene release test (CAST) and dot-blot analysis. RESULTS: IDR to CMC was
      positive at a concentration of 10 microg/ml. BAT and CAST were positive. Specific
      IgE were identified using dot-blot analysis. DISCUSSION: This is the third report
      of CMC-specific IgE and the second of anaphylaxis to CMC associated with a barium
      suspension in contact with GI tract mucosa. CMC as an excipient in medicinal
      products may therefore be a risk factor for severe anaphylaxis after injection or
      following contact with GI tract mucosa. Sensitization and allergic reactions by
      CMC in food additives have to be considered.

PMID- 20128231
TI  - Efficacy, safety and tolerability of sublingual monomeric allergoid in tablets
      given without up-dosing to pediatric patients with allergic rhinitis and/or
      asthma due to grass pollen.
AB  - The efficacy and safety of monomeric allergoid (Lofarma, Milan) have been
      demonstrated in adults but very few studies have examined it in children. This
      study therefore investigated the efficacy and safety of this sublingual
      immunotherapy (SLIT) at the dosage of 1000 AU five times a week without any up
      dosing. Forty allergic children (17 M and 23 F, mean age 7 years, range 4-16
      years), 16 with rhinitis and 24 with rhinitis and asthma, were randomized to SLIT
      or drug therapy. All the patients were sensitized to grass; some were also
      sensitized, though to a lesser extent, to Parietaria, Olea and Betulaceae. The
      patients were treated pre-/co-seasonally for two years. A visual analogue scale
      (VAS) was used at baseline and at the end of the first and second pollen seasons
      to rate the patients' well-being. The VAS score was significantly higher after
      both the first and the second year of treatment in the SLIT group than in the
      controls (p<0.05). It improved in comparison to baseline only in the active
      group. All 40 children tolerated the therapy very well. The monomeric allergoid
      at the dosage of 5000 AU/week thus appears to have a good efficacy and safety
      profile in children.

PMID- 20128232
TI  - Antihistamines do not inhibit the flare induced by the intradermal injection of
      autologous plasma in chronic urticaria patients.
AB  - BACKGROUND: There is some evidence suggesting that factors other than
      autoantibodies to FceRI or IgE and histamine released from mast cells may play a
      role in skin autoreactivity that characterizes many patients with chronic
      urticaria (CU) and, possibly, in the pathogenesis of this disease. OBJECTIVE: The
      effect of antihistamine treatment on autologous plasma skin test (APST) in
      patients with CU was assessed. METHODS: 24 patients with CU underwent autologous
      plasma skin test (APST) as well as SPT with histamine 10 mg/ml while taking
      antihistamines. In 6 cases the same tests had been carried out also before the
      start of antihistamine treatment. Plasma levels of D-dimer, prothrombin F 1+2
      fragment, and vascular endothelial growth factor (VEGF) were measured in 21
      patients. RESULTS: 21/24 (87%) patients showed a large flare on APST while taking
      antihistamines while the skin reaction to histamine 10 mg/ml was abolished or
      negligible. Little difference in the autologous plasma-induced flare was seen
      before and after the start of cetirizine therapy in 6 cases, whereas the drug
      exerted a marked effect on the histamine SPT as well as on the autologous plasma
      induced wheal. The APST-induced flare was not associated with patients' response
      to antihistamine. Plasma levels of VEGF, prothrombin F 1+2 fragment, and D-dimer
      were increased in plasmas from 8, 9, and 2 patients, respectively. CONCLUSIONS:
      Factors other than histamine are probably involved in the flare following APST in
      CU; such factors might play a pathogenic role particularly in patients not
      responding to standard antihistamine treatments.

PMID- 20128233
TI  - Paradoxical exacerbation of chronic urticaria by H1-antihistamines and
      montelukast.
AB  - Histamine is the main mediator of urticaria and H1-receptor antagonists represent
      the treatment of choice in all patients with chronic urticaria. Leukotriene
      receptor antagonists as montelukast have also been used in patients with chronic
      urticaria unresponsive to H1-antihistamines alone. We report a patient with
      chronic urticaria whose disease was paradoxically exacerbated by H1
      antihistamines and montelukast, and controlled by immunosuppressive drugs as
      ciclosporin and azathioprine. Urticaria exacerbations were caused by different
      molecules including either piperidine (fexofenadine, desloratadine, ebastine,
      rupatadine) or piperazine (hydroxyzine, cetirizine) derivatives as well as by
      montelukast suggesting that an IgE-mediated mechanism was not involved. A
      possible explanation of the observed urticaria exacerbation is that H1
      antihistamines and montelukast may shift the H1 histamine receptor and the
      leukotriene receptor to the active conformation instead of the inactive state.
      The beneficial effects of ciclosporin and azathioprine confirm that
      immunosuppressive drugs have an important role in the treatment of refractory
      chronic urticaria and back the hypothesis that an autoimmune/autoreactive
      mechanism often underlies the disease.

PMID- 20128234
TI  - New developments improve food allergy management.

PMID- 20128235
TI  - Six new species of coccidia (Apicomplexa: Eimeriidae) from endangered Phelsuma
      spp. geckoes (Sauria: Gekkonidae) of the Black River Gorges National Park,
      Mauritius.
AB  - Six new species of coccidia are described from endangered Phelsuma spp. geckoes
      (Sauria: Gekkonidae) endemic to Mauritius, Indian Ocean. Five new species (3
      Eimeria and 2 Isospora species) are described from Phelsuma rosagularis Vinson et
      Vinson; all lack a micropyle and an oocyst residuum, and all have a sporocyst
      residuum. Oocysts of Eimeria swinnertonae sp. n. are ellipsoidal, 22.2 x 17.8
      (20.8-24.8 x 16.8-18.4) microm; SI 1.25; polar granule absent. Sporocysts are
      ellipsoidal, 8.8 x 7.0 (8.0-9.6 x 6.4-8.0) microm; SI 1.3; Stieda body absent.
      Oocysts of Eimeria stebbinsi sp. n. are ellipsoidal, 17.4 x 11.7 (16.0-19.2 x
      11.2-12.8) microm; SI 1.5; polar granules present. Sporocysts are elongate
      ellipsoidal, 7.7 x 4.0 (7.2-8.0 x 3.2-5.6) microm; SI 1.9; Stieda body present.
      Oocysts of Eimeria raleighi sp. n. are spheroidal to sub-spheroidal, 17.0 x 15.5
      (16.0-19.2 x 14.4-16.8) microm; SI 1.1; polar granule present. Sporocysts are sub
      spheroidal, 7.8 x 6.6 (7.2-8.0 x 6.4-7.2) microm; SI 1.2; Stieda body absent.
      Oocysts of Isospora cottinghamae sp. n. are ellipsoidal, 19.8 x 15.5 (17.6-21.6 x
      14.4-17.6) microm; SI 1.3; polar granules present. Sporocysts are ellipsoidal,
      10.8 x 6.9 (9.6-12.8 x 6.4-8.0) microm; SI 1.6; Stieda body present. Oocysts of
      Isosporapearlae sp. n. are ellipsoidal, 16.0 x 11.5 (15.2-17.6 x 9.6-12.8)
      microm; SI 1.4; polar granule present. Sporocysts are ellipsoidal, 8.8 x 5.4 (8.0
      9.6 x 4.8-6.4) microm; SI 1.6; Stieda and substieda bodies present. One new
      Eimeria species is described from the blue-tailed day gecko, Phelsuma cepediana
      Merrem. Oocysts of Eimeria hartleyi sp. n. are sub-spheroidal to ellipsoidal,
      18.2 x 14.5 (16.0-20.8 x 13.6-16.0) microm; SI 1.26; polar granules present.
      Sporocysts are ellipsoidal to cylindroidal, 7.5 x 5.3 (6.4-8.0 x 4.8-6.4) microm;
      SI 1.4; Stieda body present. We report the presence of tetrazoic spheroidal to
      sub-spheroidal oocysts or sporocysts 10.2 x 8.5 (9.9-10.4 x 8.3-8.8) microm; SI
      1.2 from an individual of P. cepediana. These oocysts or sporocysts are
      significantly larger than the Cryptosporidium species so far described from
      reptiles, and likely represent excretion of spuriously ingested sporocysts of a
      Sarcocystis or Adelina coccidian.

PMID- 20128236
TI  - CD4+CD25+Foxp3+ regulatory T cells prevent the development of Th1 immune response
      by inhibition of dendritic cell function during the early stage of Plasmodium
      yoelii infection in susceptible BALB/c mice.
AB  - Protective immunity against murine malaria infection depends largely on the
      establishment of effective Th1 immune response during the early stages of
      infection. Experimental data suggest that the death of Plasmodium yoelii 17XL (Py
      17XL) susceptible BALB/c mice results from the suppression of Th1 immune response
      mediated by CD4+CD25+Foxp3+ regulatory T cells (Tregs). However, the mechanism by
      which Tregs regulate Th1 immune response is poorly understood. Since immunity is
      initiated by dendritic cells (DCs), we analysed DC responses to Py 17XL in
      control and Treg-depleted BALB/c mice. Myeloid DC proliferation, phenotypic
      maturation and interleukin-12 (IL-12) production were strongly inhibited in
      control BALB/c mice. In contrast, plasmacytoid DC proliferation and IL-10
      production were strongly enhanced in control BALB/c mice. In-vivo depletion of
      Tregs resulted in significantly reversed inhibition of DC response, which may
      contribute to the establishment of Th1 immune response, indicating that Tregs
      contribute to the suppression of Th1 immune response during malaria. These
      findings suggest Tregs contribute to prevent Th1 immune response establishment
      during the early stage of Py 17XL infection by inhibiting DC response.

PMID- 20128237
TI  - Response of rainbow trout (Oncorhynchus mykiss) in skin and fin tissue during
      infection with a variant of Gyrodactylus salaris (Monogenea: Gyrodactylidae).
AB  - Response mechanisms of rainbow trout Oncorhynchus mykiss (Walbaum),
      experimentally infected with a Danish strain of Gyrodactylus salaris Malmberg,
      1957 were investigated using molecular tools (qPCR) and immunohistochemistry.
      Expression of ten immune-relevant genes and reactivity with five different
      antibodies in the epidermis of skin and fin tissue were analysed in susceptible
      but responding rainbow trout. Rainbow trout were susceptible with regard to the
      parasite strain which initially colonised fins but relocated to the body region
      as infection progressed. The ten investigated genes encoding the cytokines IL
      1beta, TNF-alpha, IFN-gamma, IL-10 and markers for adaptive immune activity, such
      as CD-4, CD-8, TCR-alpha, IgM, IgT and MHC II, were not found significantly
      regulated during the course of infection although IFN-gamma showed a slight up
      regulation. Immunohistochemical analyses showed positive reactivity with
      antibodies against CD3, B-lymphocytes, neutrophilic granulocytes and collectin
      but not with mAb against IgM. No staining differences between infected and non
      infected skin and fin tissue were detected.

PMID- 20128238
TI  - Lectinhistochemical detection of terminal carbohydrate residues in the enteric
      myxozoan Enteromyxum leei parasitizing gilthead seabream Sparus aurata (Pisces:
      Teleostei): a study using light and transmission electron microscopy.
AB  - The presence of terminal carbohydrate residues in Enteromyxum leei (Diamant, Lom
      et Dykova, 1994) Palenzuela, Redondo et Alvarez-Pellitero, 2002 stages in
      gilthead seabream intestines was studied at light microscopy (LM) and
      transmission electron microscopy (TEM) level using lectin histochemical
      techniques. Abundant mannose and/or glucose residues were demonstrated by the
      intense staining caused by binding of biotinylated concanavalin A (Con A), at
      both LM and TEM. A clear positivity was also obtained with Ulex europaeus (UEA I)
      agglutinin specific for fucose residues. Both lectins stained E. leei
      proliferative and sporogonic stages, though glycan patterns varied between these
      developmental stages. Wheat germ agglutinin (WGA) and Bandeiraea simplicifolia
      lectin I (BSL I) recognised only structures in the sporogonic stages. Faint
      labelling occurred with Glycine max (SBA) lectin. No staining was obtained with
      Sambucus nigra (SNA) agglutinin. The TEM studies demonstrated a restricted
      presence of N-acetyl-D-galactosamine and alpha-D-galactose, whereas
      glucose/mannose and fucose, the dominant structures, were also present at the
      parasite membranes and host-parasite interface, suggesting a role in host
      parasite interaction.

PMID- 20128239
TI  - Species of Strigea (Digenea: Strigeidae), parasites of the savanna hawk
      Buteogallus meridionalis (Aves: Accipitridae) from Argentina, with the
      description of a new species.
AB  - A new strigeid digenean, Strigea meridionalis sp. n., is described from the small
      intestine of the savanna hawk, Buteogallus meridionalis (Latham) (Aves:
      Accipitridae), from Formosa Province, Argentina. This species is characterised by
      the absence of a neck region in the hindbody, the presence of entire testes, a
      copulatory bursa with a membranous fold originated from the muscular ring
      (Ringnapf) and by the arrangement of vitelline follicles in the forebody. Other
      two strigeid species collected from the savanna hawk, Strigea elliptica (Brandes,
      1888) and Strigea microbursa Pearson et Dubois, 1985, are described and
      illustrated. Strigea microbursa is reported for the first time from the
      Neotropical Region and B. meridionalis represents a new host record for S.
      elliptica. These findings allow us to increase the knowledge of these species,
      adding new metric and morphological data. A key to the species of the Neotropical
      Strigea Abildgaard, 1790 is presented including data on their geographical
      distribution.

PMID- 20128240
TI  - Ultrastructure of spermiogenesis and mature spermatozoon of Triaenorhina
      rectangula (Cestoda: Cyclophyllidea: Paruterinidae).
AB  - Ultrastructural characters of spermiogenesis and mature spermatozoon of
      Triaenorhina rectangula (Fuhrmann, 1908) are examined by transmission electron
      microscopy. Spermiogenesis follows the Ba and Marchand's Type III spermiogenesis
      of cestodes. The process begins with the formation of a differentiation zone
      containing two centrioles and a cytoplasmic protrusion. The centrioles are
      associated with vestigial striated roots. One of the centrioles develops a free
      flagellum externally to the cytoplasmic protrusion. After a slight rotation, the
      free flagellum fuses with the cytoplasmic protrusion. In the final stage of
      spermiogenesis, a single crested body appears in the anterior part of the
      differentiating spermatozoon. The anterior extremity of the mature spermatozoon
      is characterised by an apical cone and a single crested body. The axoneme is of
      the 9+"1" trepaxonematan type. A periaxonemal sheath and electron-dense rods are
      described in some parts of the mature spermatozoon. The nucleus is electron-dense
      and spirally coiled around the axoneme. The cortical microtubules are spirally
      arranged at an angle of about 40 degrees to the spermatozoon axis. The present
      results show that the ultrastructural characters of spermiogenesis and mature
      spermatozoon of T. rectangula resemble most closely those in taeniids and
      metadilepidids. The comparison of these results with the only previous
      spermiological description of a paruterinid species reveals differences relative
      to the occurrence of filamentous rods of electron-dense material versus
      intracytoplasmic walls in the mature spermatozoon that may reflect the
      polyphyletic character of the Paruterinidae.

PMID- 20128241
TI  - New name for Progrillotia dollfusi Carvajal et Rego, 1983 (Cestoda:
      Trypanorhyncha): description of adults from Squatina guggenheim (Chondrichthyes:
      Squatiniformes) off the coast of Argentina.
AB  - Examination of the type material of Progrillotia dollfusi Carvajal et Rego, 1983,
      and of new specimens recently collected off the coast of Argentina (including
      plerocerci from 10 species of teleosts and adults from Squatina guggenheim
      Marini), allowed a detailed redescription of this species and the evaluation of
      its current taxonomic status. The following characters that have been treated
      inconsistently by different authors have been herein corrected or confirmed: band
      of hooklets on external surface restricted to the base of the tentacle, external
      surface of metabasal region with 3-5 intercalary hooks arranged in a single row
      merging immediately to a cluster of 3-4 hooklets arranged in two rows; retractor
      muscle originating in the posterior third of the bulb, hollow hooks, and
      posterior margin of bothria notched. These features along with the presence of
      postovarian testes in the adults clearly confirm the placement of P. dollfusi in
      the genus Grillotia Guiart, 1927. In order to avoid the homonymy with Grillotia
      dollfusi Carvajal, 1971, a new name, Grillotia carvajalregorum nom. n., is
      proposed. This species differs from the 16 valid species in the genus in the
      combination of the following characters: number and morphology of hooks in
      principal rows in proximal metabasal region of the tentacle, number and
      distribution of intercalary hooks, presence of clusters of hooklets, extent of
      band of hooklets on external surface of basal armature, site of origin of the
      retractor muscle, and features of the terminal genitalia. The present study
      describes the plerocerci and adult worms, and provides detailed description of
      the microthrix pattern and histology of this species for the first time.

PMID- 20128242
TI  - Pseudoacanthocephalus lutzi (Hamann, 1891) comb. n. (Acanthocephala:
      Echinorhynchidae) for Acanthocephalus lutzi (Hamann, 1891), parasite of South
      American amphibians.
AB  - Acanthocephalus lutzi (Hamann, 1891) is proposed to be transferred to the genus
      Pseudoacanthocephalus Petrochenko, 1956 based on the type material from Rhinella
      marina (L.) from Brazil and recently collected material from R. arenarum (Hensel)
      from Argentina. Pseudoacanthocephalus is characterised by the following features:
      a cylindrical trunk without spines, a cylindrical proboscis, testes in tandem, a
      compact cluster of cement glands, a nearly terminal male genital pore, a ventral
      and sub-terminal female genital pore, and egg without polar prolongations,
      containing a holoechinate acanthor. Pseudoacanthocephalus lutzi comb. n. has a
      proboscis armature of 14-18 longitudinal rows of 5-8 hooks each, with all roots
      formed by a posteriorly directed longitudinal spatulate sheet having a central
      rib, and an inconspicuous sheet directed anteriorly; a variable number (4, 5 or
      6) of cement glands; a cerebral ganglion located near the base of the proboscis
      receptacle; digitiform to claviform lemnisci, as long as, or slightly shorter or
      slightly longer than the proboscis receptacle; a sigmoid-shaped posterior end in
      males; an egg with a conspicuous fibrillar coat; and one of the larval hooks more
      robust and different in shape than the others. Additionally, the type material of
      Acanthocephalus saopaulensis Smales, 2007 from Rhinella icterica (Spix) from
      Brazil and a paratype of A. caspanensis Fernandez et Ibarra Vidal, 1992 from R.
      spinulosa (Wiegmann) from Chile were studied. Acanthocephalus saopaulensis is
      considered conspecific with P. lutzi and A. caspanensis is transferred to
      Pseudoacanthocephalus because it possesses all the characters of the genus
      mentioned above. The use of characters such as egg morphology and host ecology
      for distinguishing Acanthocephalus from Pseudoacanthocephalus is also discussed.

PMID- 20128243
TI  - Redescription of Spinitectus tabascoensis (Nematoda: Cystidicolidae) from fishes
      of the Lacandon rain forest in Chiapas, southern Mexico, with remarks on
      Spinitectus macrospinosus and S. osorioi.
AB  - Two little-known species of Spinitectus (Nematoda: Cystidicolidae) were, for the
      first time, recorded from fishes of the Lacantun River (Usumacinta River basin)
      in the Lacandon rain forest, Chiapas, southern Mexico: S. tabascoensis Moravec,
      Garcia-Magana et Salgado-Maldonado, 2002 in intestines of Ictalurus furcatus
      (Valenciennes) (Ictaluridae) (adults and juveniles), Cathorops aguadulce (Meek)
      and Potamarius nelsoni (Evermann et Goldsborough) (both Ariidae) (in both only
      juveniles), and S. osorioi Choudhury et Perez-Ponce de Leon, 2001 in Atherinella
      alvarezi (Diaz-Pardo) (Atherinopsidae) (adults in intestine) and Eugerres
      mexicanus (Steindachner) (Gerreidae) (adults and juveniles in stomach). Eugerres
      mexicanus, C. aguadulce and P. nelsoni represent new host records. Detailed light
      and electron microscopical studies of S. tabascoensis revealed some taxonomically
      important, previously not observed features, such as cuticular spines arranged in
      four sectors, the cephalic structure, the number (2) of ventral precloacal ridges
      or the structure of the male caudal end. Therefore, Spinitectus tabascoensis is
      redescribed. Spinitectus macrospinosus Choudhury et Perryman, 2003, described
      from ictalurids in Canada and the USA, is considered its junior synonym.
      Spinitectus tabascoensis seems to be a specific parasite of Ictalurus spp.,
      whereas C. aguadulce and P. nelsoni, as well as some other fishes, serve only as
      its paratenic hosts. The definitive hosts of S. osorioi are atherinopsid fish (A.
      alvarezi, Chirostoma spp.), whereas the gerreid E. mexicanus probably serves only
      as its postcyclic host.

PMID- 20128244
TI  - Acanthochondria serrani sp. n. (Copepoda: Chondracanthidae) parasitic on Serranus
      auriga (Perciformes: Serranidae) from Argentinean waters.
AB  - A new species of Acanthochondria Oakley, 1927 (Copepoda, Poecilostomatoida,
      Chondracanthidae), parasitic on Serranus auriga (Cuvier) from the Argentinean
      coastal zone, is described and illustrated. The new species differs from its
      congeners by the relative length of the neck and the protopod of leg 2. This is
      the second record of this genus for the South-eastern Atlantic and the first one
      from a serranid host.

PMID- 20128245
TI  - First description of the male of Philometra filiformis (Nematoda: Philometridae),
      a gonad-infecting parasite of the marine fish Pagellus erythrinus (Sparidae) in
      Mediterranean.
AB  - The male of the gonad-infecting nematode Philometra filiformis (Stossich, 1896)
      (Philometridae) is for the first time described, based on specimens from the
      ovary of the marine fish Pagellus erythrinus (Linnaeus) from the Tyrrhenian Sea
      off Sicily, Italy. It is mainly characterized by the testis extending anteriorly
      nearly to the anterior end of body, the oesophagus without a usual anterior
      inflation, the absence of a dorsal barb or distinct transverse lamellae on the
      tip of the gubernaculum, the measurements of the spicules and the gubernaculum,
      and a fairly long body.

PMID- 20128246
TI  - [Psychiatric epidemiology--recent advances].
AB  - The aim of this article is to review recent advances and the latest research
      trends in psychiatric epidemiology. Examination of mental disorders prevalence
      delivers important information about the mental state of society and need for
      professional psychiatric care. The 12 months prevalence estimates are 30% for any
      mental disorders. Knowledge about historical methods of data collecting helps to
      understand psychiatric epidemiology better. We overview few generations of
      research that differ in methodology. The most common difficulties observed during
      that kind of research will be described. Available methods of examination of
      mental disorders prevalence will be presented in this article. The most
      significant results of international WHO epidemiologic project will be discussed.
      We also point out future challenges for psychiatric epidemiology and predict the
      systemic solutions that make intercultural comparisons possible.

PMID- 20128247
TI  - [Akathisia--diagnosis, pathophysiology and therapy].
AB  - Akathisia is an atypical disorder (or the symptom) of the motor system standing
      on the border of neurology and psychiatry. In neurology, akathisia is a disorder
      resulting mainly from disturbed dopaminergic transmission; in the field of
      psychiatry it is recognized as one of the extrapiramidal side effects during the
      treatment with neuroleptics. The paper describes the historical context of
      disorder defined as akathisia, its clinical course, pathophysiology, as well as
      therapy.

PMID- 20128248
TI  - [Some questions about the essence of delusions in the light of recent
      neurobiological findings].
AB  - Formation of delusions in the phase of acute psychosis is based on two subsequent
      processes. The first one is dopamine hyperactivity in mesolimbic neural pathways,
      the second one is a cognitive process of up-down attribution of meanings of this
      subjectively perceived state of mind by the higher levels of brain. After the
      successful antipsychotic treatment, the subjectivity of patients changes. When
      the state of acute psychosis resolves patients must re-interpret this new
      emerging subjective experience. These interpretations are often incorrect and
      bizarre. In most cases they are regarded as delusions (sometimes "chronic
      delusions"). The question asked in the presented paper is whether they are truly
      delusions. The essence of delusion must include in the same time an active
      neurobiological basis of delusion (hyperdopaminergic state) and its cognitive
      level. It's not clear what is the proper term for the phenomenon when only
      incorrect or bizarre cognitive convictions are present after successful treatment
      of psychosis, but without dopaminergic hyperactivity.

PMID- 20128249
TI  - [Influence of positive and negative symptoms on suicidal behaviour in
      schizophrenia. Review of current literature].
AB  - Suicide is the main cause of death among persons with schizophrenia. The risk of
      suicide among this group is continually high and it is estimated at 10%. The aim
      of the study was a review of current literature concerning positive and negative
      symptoms on suicidal behaviour in schizophrenia. Some studies showed, that the
      active phase of the disease and worsening of the sickness increase the risk of
      suicide among those diagnosed with schizophrenia. It is contradictory to the
      works, which prove that suicide of a schizophrenic person is not a result of
      experiencing psychotic symptoms. According to literature on the subject, the
      influence of positive symptoms on the incidence of suicide attempts made in
      schizophrenia is still inconclusive, also researchers' opinions about the
      negative symptoms are divided. None of the hitherto studies present statistically
      significant proof that commanding auditory hallucinations increase the risk of
      suicide among schizophrenics. The results of the investigations quoted below did
      not allow to unambiguously recognize the influence of positive and negative
      symptoms on suicidal behaviour, as well as to qualify them to a group of risk
      factors or a group of variables, playing a protective role.

PMID- 20128250
TI  - [The characteristic of population participating in a community-based
      rehabilitation program].
AB  - AIM: The difficulties in social functioning of the mentally ill are widely
      documented in specialist literature. The social affects addressed to the mentally
      disabled are an attempt to overcome this particular disability. The aim of the
      presented research is the characterization of the social group participating in a
      community-based rehabilitation program realized on Warsaw area. METHOD: 103 long
      term patients with mental disorders provided with a community-based
      rehabilitation program were the participants in the study. They were not
      hospitalized at the time when the research was conducted. The following
      instruments were used: the Questionnaire and Map of Social Support by Bizon, the
      individual interview, and the questionnaire especially prepared for the needs of
      this research. RESULTS: The studied group consists of people with a long-standing
      period of illness, with numerous hospitalizations, constantly remaining under
      psychiatric care. The tested persons are singles and demanding a strong social
      support. Their individual social networks of support are sparse and in a large
      part compensated by therapists from the support institution. The tested group
      highly values the influence of the local rehabilitation program on their
      functioning. CONCLUSIONS: The chronically mental ill persons show numerous
      difficulties in their social functioning. Participation in the social support
      programs protects them against successive hospitalizations. During the last year,
      preceding the research, the amount of hospitalizations was significantly lower
      than in the period preceding the taking care by the local systems. It is
      necessary to treat the local rehabilitation programs as an effective mechanism
      supporting the functioning of the chronically mental ill people.

PMID- 20128251
TI  - [Involvement Evaluation Questionnaire--description and application].
AB  - Long-term mental illnesses such as schizophrenia or affective disorders often
      impose a burden on the patients who suffer from it, as well as on their carers
      (relatives or friends). There are many instruments measuring family or caregiver
      burden. One of these instruments is the Involvement Evaluation Questionnaire
      (IEQ). The IEQ is a 31-item questionnaire which is completed by the caregiver.
      The IEQ contains 27 items that can be divided into four subscales (domains):
      tension (nine items), worrying (six items), supervision (six items) and urging
      (eight items). Two items appear in more than one domain. The items are scored on
      a 5-point Likert scale (never, sometimes, regularly, often and always). There is
      no full Polish adaptation of IEQ so far. The psychometric properties of the IEQ
      and its culture-profiled versions are satisfying and comparable. The IEQ, as a
      self-assessment instrument, is easy to administer and not time-consuming. The IEQ
      proved to be a reliable instrument for measuring caregiver consequences in mental
      healthcare.

PMID- 20128252
TI  - [Psychological intervention in binge eating disorder].
AB  - Binge eating disorder (BED) is a specific example of an eating disorder. It
      consists of loosing control of eating without compensatory behaviours like
      purging. AIM: To characterize considerations and consequences of BED and to
      propose therapy intervention useful in the treatment of BED. METHOD: Relevant
      studies were examined and summarized in the form of a narrative review. The
      author's own proposal of psychological intervention was presented. RESULTS: BED
      is common, especially in obese people. It makes loosing weight difficult. One of
      the most effective methods of curing it, is psychotherapy. The proposed
      psychological intervention for BED includes the following aspects: analysis,
      consciousness, relaxation, control, and distance. This is a register of specific
      advice for an ill person. CONCLUSIONS: The treatment of BED is a process. It
      takes time and consists of a gradual decrease of symptoms. The aim of the therapy
      is the acquisition of control in the range of one's own eating behaviours and
      psychological states.

PMID- 20128253
TI  - [Application of group psychotherapy in treatment of adolescents and young women
      with anorexia nervosa (presentation of therapeutic work model in the Neurosis and
      Eating Disorders Treatment Centre "Dabrowka"--the author's own experience)].
AB  - The article shows chosen motives from the authors self experience in the
      specificity and principles of conducting group psychotherapy in treating patients
      with a diagnosis of anorexia nervosa. In the first part of the article, the
      author presents elementary postulates of the working model in teenage therapeutic
      groups in the Neurosis and Eating Disorders Treatment Centre "Dabrowka", in the
      years 2002-2004. The second part presents basic postulates of adult group
      psychotherapy practiced in the "Dabrowka" Centre. Conclusions indicate the main
      elements of a group therapy process in patients with anorexia nervosa.

PMID- 20128255
TI  - The H1N1 pandemic: doing what we do best--back to basics.

PMID- 20128254
TI  - [Asperger's disorder diagnosed in the man treated with chronic and resistant
      emotional and behavioral disturbances--the case report].
AB  - Asperger's disorder is a nosologic phenomena, that is similar to autism, and
      falls under the category of pervasive developmental disorders. The unknown and
      probably multi-factor aetiology, wide clinical picture and not completely defined
      and clinically relevant diagnostic criteria are the topic of discussion between
      investigators and clinicians. In the article presented, a single case report of a
      39-year old male patient, diagnosed and treated for years due to chronic and
      resistant emotional and behavioural disturbances, not clearly defined psychotic
      symptoms and dominating dysfunctions of social involvement, may be a voice in the
      debate about Asperger's disorder spectrum, comorbidity in Asperger's syndrome and
      serve to remind the clinicians, that pervasive developmental disorders could
      really be diagnosed in adults.

PMID- 20128256
TI  - A survey of infection prevention and control resources in acute care facilities
      across British Columbia.
AB  - BACKGROUND: To determine the gaps in infection prevention and control (IPAC)
      resources and the disparities between rural and urban areas, the Provincial
      Infection Control Network surveyed the current resources in British Columbia
      (BC). METHODS: Acute care facilities (ACF) in six health authorities (HA) were
      surveyed for IPAC staff; distribution of work; infection prevention and control
      professional (ICP) to bed ratios; and teaching activities. HAs were designated as
      either urban or rural. RESULTS: Responses represented 54 (68%) of the ACF in BC.
      Rural HAs showed a significantly higher number of inexperienced ICPs (68% vs.
      17%; p < 0.001). Only 22 (60%) of eligible ICPs were Certification Board of
      Infection Control certified. Five out of six HAs (83%) reported having an IPAC
      physician. Acute care ICP to bed ratios ranged from one per 67 to one per 175 and
      combined acute and long-term care ICP to bed ratios ranged from one per 270 beds
      to one per 525 beds. The number of ICPs who reported working overtime on a
      consistent basis ranged from 20 to 100%. CONCLUSIONS: ACFs surveyed did not meet
      the recommended standards for staffing and IPAC resources in order to function as
      an effective program. Surveys of infection control resources are valuable tools
      to identify needs and assist in acquiring the resources to fill the identified
      gaps within a health authority.

PMID- 20128257
TI  - Creating a mentoring culture to connect and empower new ICPs, part one.
AB  - This article discusses how to empower new ICPs by creating a mentoring culture. A
      brief history of mentoring is provided along with rationale for why mentoring is
      so critical in today's healthcare environment. Mentorship is contrasted and
      compared with preceptorship and coaching to elucidate those elements that are
      distinct to mentoring. The characteristics of an effective mentor, benefits of
      mentoring and phases of a mentoring relationship are described. Finally, the
      potential flashpoints that can occur in a mentoring relationship are reviewed. In
      the current healthcare environment, the growth and development of infection
      prevention and control professionals (ICPs) is essential to maintain quality
      outcomes. As provincial governments move to mandatory reporting of patient
      indicators there will be an increased demand for these professionals at a time
      when supply is dwindling. While recruitment into the profession is important,
      retaining experienced ICPs is also an issue. The purpose of this article is to
      discuss why mentoring in infection prevention and control (IPAC) matters, to
      identify what mentoring is and is not, and to present information on empowering
      staff through mentoring relationships.

PMID- 20128258
TI  - Quality control is indispensable for automated dilution systems with accelerated
      hydrogen peroxide.
AB  - BACKGROUND: Hamilton Health Sciences (HHS) is a large teaching hospital with over
      1000 beds consisting of three acute care sites, one regional cancer center and
      two rehabilitation/complex chronic care facilities. The use of chemical dilution
      control systems to dilute concentrated accelerated hydrogen peroxide (AHP)
      disinfectant to an ideal strength for effective environmental decontamination is
      a growing trend in healthcare. These systems, compared to manual dilution
      methods, are economical, efficient and promote a safer workplace. However,
      quality control (QC) and preventative maintenance standards to ensure performance
      are lacking in the environmental and healthcare cleaning industries. The
      automated systems used to dilute concentrated AHP products for disinfection
      cleaning were assessed for reliability at HHS-Henderson acute care site. METHOD:
      The control systems used on three clinical units to dilute concentrated AHP
      products, 7% Percept at 1:16 dilution (0.5%) and 3% PerDiem at 1:256 dilution
      (0.01%), were evaluated daily for reliability over 30 days. Virox AHP indicator
      test strips were used once a day to check use-dilution of Percept at 5000 parts
      per million (ppm) AHP and PerDiem at 100 ppm AHP.QC was repeated if the initial
      test was outside the acceptable range. Vendor service was arranged for the
      dilution system when repeat QC failed. Ready-to-use AHP product was employed
      until the system was functional. RESULTS: Overall, nine QC failures were detected
      on all systems during a 30-day testing period, specifically, five failures on one
      system, three on the second and one on the third. Seven failures involved Percept
      with results at < or =500 ppm, well below the acceptable 5000 ppm concentration,
      and two involved PerDiem at 500 ppm, well above the required concentration.
      CONCLUSION: Disinfectants must be used in the dilution specified by the
      manufacturer for optimal decontamination. Although there are benefits with using
      automated dilution systems in healthcare settings, findings show that attention
      must be given to quality control and preventative maintenance to ensure optimum
      results.

PMID- 20128259
TI  - SAAVI HIV vaccine trials--one small step for humankind.

PMID- 20128260
TI  - Protecting the public and guiding the profession?

PMID- 20128261
TI  - OSD furore--SAMA bloodied but unbowed.

PMID- 20128262
TI  - Incompetent, unaccountable managers paralysing health care.

PMID- 20128263
TI  - Experts review Motsoaledi's first 3 months.

PMID- 20128264
TI  - Assisting victims of sexual offences: ensuring a professional service by the SAPS
      -how it affects medical practitioners.

PMID- 20128265
TI  - Malignant otitis externa with ecthyma gangrenosum and pneumonia in an infant.

PMID- 20128266
TI  - A striking 'Natal' experience.

PMID- 20128267
TI  - Severe acute respiratory infection with influenza A (H1N1) during pregnancy.

PMID- 20128268
TI  - HIV transmission from mother to child--HAART compared with dual therapy.

PMID- 20128269
TI  - Effectiveness of community participation in tuberculosis control.

PMID- 20128270
TI  - CFTR structural rearrangements are not a major mutational mechanism in black and
      coloured southern African patients with cystic fibrosis.

PMID- 20128271
TI  - Prerequisites for national health insurance in South Africa: results of a
      national household survey.
AB  - BACKGROUND: National Health Insurance (NHI) is currently high on the health
      policy agenda. The intention of this financing system is to promote efficiency
      and the equitable distribution of financial and human resources, improving health
      outcomes for the majority. However, there are some key prerequisites that need to
      be in place before an NHI can achieve these goals. OBJECTIVES: To explore public
      perceptions on what changes in the public health system are necessary to ensure
      acceptability and sustainability of an NHI, and whether South Africans are ready
      for a change in the health system. METHODS: A cross-sectional nationally
      representative survey of 4 800 households was undertaken, using a structured
      questionnaire. Data were analysed in STATA IC10. RESULTS AND CONCLUSIONS: There
      is dissatisfaction with both public and private sectors, suggesting South
      Africans are ready for health system change. Concerns about the quality of public
      sector services relate primarily to patient-provider engagements (empathic staff
      attitudes, communication and confidentiality issues), cleanliness of facilities
      and drug availability. There are concerns about the affordability of medical
      schemes and how the profit motive affects private providers' behaviour. South
      Africans do not appear to be well acquainted or generally supportive of the
      notion of risk cross-subsidies. However, there is strong support for income cross
      subsidies. Public engagement is essential to improve understanding of the core
      priniciples of universal pre-payment mechanisms and the rationale for the
      development of NHI. Importantly, public support for pre-payment is unlikely to be
      forthcoming unless there is coinfidence in the availability of quality health
      services.

PMID- 20128274
TI  - Trends in adult tobacco use from two South African Demographic and Health Surveys
      conducted in 1998 and 2003.
AB  - INTRODUCTION: Since peaking in the early 1990s in South Africa, tobacco use has
      declined significantly. The reduction has been attributed to the government's
      comprehensive tobacco control policies that were introduced at the time.
      OBJECTIVE: To assess the pattern of tobacco use in the South African Demographic
      and Health Surveys of 1998 and 2003. METHODS: Multi-stage sampling was used to
      select approximately 11 000 households in cross-sectional national surveys. Face
      to-face interviews, conducted with 13 826 adults (41% men) aged > or = 15 years
      in 1998, and 8 115 (42% men) in 2003, included questions on tobacco use according
      to the WHO STEP-wise surveillance programme. Logistic regression analysis was
      used to assess the independent effects of selected characteristics on smoking
      prevalence. RESULTS: Daily or occasional smoking prevalence among women remained
      unchanged at 10 - 11%; it decreased among men from 42% (1998) to 35% (2003). The
      decline for men was significant among the poorest and those aged 25 - 44 years.
      Strong age patterns were observed, peaking at 35 - 44 years, which was reduced
      among men in 2003. Higher income and education were associated with low
      prevalence of smoking, while living in urban areas was associated with higher
      rates. Black men and women smoked significantly less than other population
      groups. CONCLUSION: Despite decreased smoking rates in some subgroups, a lapse
      exists in the efforts to reduce tobacco use, as smoking rates have remained
      unchanged among women, and also among young adults aged 15 - 24 years.

PMID- 20128272
TI  - Outcomes of the South African National Antiretroviral Treatment Programme for
      children: the IeDEA Southern Africa collaboration.
AB  - OBJECTIVES: To assess paediatric antiretroviral treatment (ART) outcomes and
      their associations from a collaborative cohort representing 20% of the South
      African national treatment programme. DESIGN AND SETTING: Multi-cohort study of 7
      public sector paediatric ART programmes in Gauteng, Western Cape and KwaZulu
      Natal provinces. SUBJECTS: ART-naive children (< or = 16 years) who commenced
      treatment with > or = 3 antiretroviral drugs before March 2008. OUTCOME MEASURES:
      Time to death or loss to follow-up were assessed using the Kaplan-Meier method.
      Associations between baseline characteristics and mortality were assessed with
      Cox proportional hazards models stratified by site. Immune status, virological
      suppression and growth were described in relation to duration of ART. RESULTS:
      The median (interquartile range) age of 6 078 children with 9 368 child-years of
      follow-up was 43 (15 - 83) months, with 29% being < 18 months. Most were severely
      ill at ART initiation. More than 75% of children were appropriately monitored at
      6-monthly intervals with viral load suppression (< 400 copies/ml) being 80% or
      above throughout 36 months of treatment. Mortality and retention in care at 3
      years were 7.7% (95% confidence interval 7.0 - 8.6%) and 81.4% (80.1 - 82.6%),
      respectively. Together with young age, all markers of disease severity (low
      weight-for-age z-score, high viral load, severe immune suppression, stage 3/4
      disease and anaemia) were independently associated with mortality. CONCLUSIONS:
      Dramatic clinical benefit for children accessing the national ART programme is
      demonstrated. Higher mortality in infants and those with advanced disease
      highlights the need for early diagnosis of HIV infection and commencement of ART.

PMID- 20128273
TI  - Childhood tuberculosis infection and disease: a spatial and temporal transmission
      analysis in a South African township.
AB  - BACKGROUND: Tuberculosis (TB) remains a leading cause of mortality and morbidity
      in South Africa. While adult TB results from both recent and past infection,
      childhood TB results from recent infection and reflects ongoing transmission
      despite current TB control strategies. SETTING: A South African community with
      high rates of TB and HIV disease. OUTCOMES: A Geographic Information System was
      used to spatially and temporally define the relationships between TB exposure,
      infection and disease in children < 15 years of age with exposure to adult HIV
      positive and HIV-negative TB disease on residential plots between 1997 and 2007.
      RESULTS: During the study period the annual adult TB notification rate increased
      from 629 to 2 106/100 000 and the rate in children aged < 15 years ranged between
      664/100 000 and 1 044/100 000. The mean number of exposures to adult TB for TB
      uninfected children, latently TB-infected children and TB cases were 5.1%, 5.4%
      and 33% per annum and the mean number of adult smear-positive cases per exposed
      child was 1.0, 1.6 and 1.9, respectively. Acquisition of TB infection was not
      associated with HIV status of the adult TB case to which the child was exposed,
      and 36% of child TB cases were diagnosed before the temporally closest adult case
      on their plot. CONCLUSIONS: Childhood infection and disease were quantitatively
      linked to infectious adult TB prevalence in an immediate social network.
      Childhood infection should be monitored in high-burden settings as a marker of
      ongoing TB transmission. Improved knowledge of township childhood and adult
      social networks could also facilitate targeted active case finding, which may
      provide an adjunct to currently failing TB control strategies.

PMID- 20128275
TI  - Influenza- and respiratory syncytial virus-associated adult mortality in Soweto.
AB  - BACKGROUND: Influenza and respiratory syncytial virus (RSV) infections cause
      seasonal excess mortality and hospitalisation in adults (particularly the
      elderly) in high-income countries. Little information exists on the impact of
      these infections on adults in Africa. OBJECTIVES: To estimate influenza- and RSV
      related adult mortality, stratified by age and hospitalisation in Soweto. STUDY
      DESIGN: A retrospective hospital-based study in Soweto from 1997 to 1999 to
      estimate influenza- and RSV-related excess all-cause deaths and hospitalisation
      using a rate-difference method. The study was based on influenza seasons of
      varying severity, provided by surveillance data. RESULTS: Influenza seasons were
      significantly associated with excess mortality in adults across all 3 years,
      except for 18 - 64-year-olds in 1998. Excess mortality was highest in those > or
      = 65 years of age: 82.8/100 000 population in the mild 1997 season and 220.9/100
      000 in the severe 1998 season. Influenza significantly increased adult medical
      hospitalisation in the severe 1998 season alone. RSV did not significantly affect
      mortality or hospitalisation. CONCLUSION: Influenza-related mortality was
      substantial and disproportionately affected the elderly. Influenza vaccination
      for the elderly warrants consideration. The RSV-related burden was not
      significantly increased but merits observation over a longer period.

PMID- 20128276
TI  - Guideline for the treatment of Parkinson's disease.

PMID- 20128277
TI  - [Concentration of airborne pollen in Beijing city with burkard sampler].
AB  - OBJECTIVE: To investigate the airborne pollen concentration in Beijing city
      during autumn and to grade the Artemisia pollen concentration. METHOD: Burkard
      volumetric trap was used to sample the airborne pollen in Beijing city from
      August 1st 2007 to October 10th 2007. Patients only allergic to mugwort pollen
      were followed up, and their symptom scores and the mugwort pollen concentration
      were analyzed statistically. RESULT: 1) Mugwort and Humulus (including Cannabis
      Sativa L) were the main airborne pollen during August and September in Beijing
      city, accounting for 31% and 51%, respectively; 2) Mugwort pollen season was from
      8th August to 8th October; 3) The daily peak concentration of Mugwort pollen was
      267 g/m3, with an average of 71 g/m3, the daily peak concentration of Humulus
      pollen was 672 g/m3, with an average of 124 g/m3; 4) 88.5% out-patients suffering
      from hay fever or asthma during Autumn were allergic to mugwort, 28.2% allergic
      to Humulus; 5) the grading of airborne Mugwort pollen concentration: 0-14 g/m3 as
      grade 0, 15-40 g/m3 as grade I, 41-116 g/m3 as grade II, more than 117 g/m3 as
      grade III. CONCLUSION: It was the first time that Burkard volumetric sampler was
      employed in monitoring Mugwort and Humulus concentration in Beijing city. Average
      concentration of mugwort pollen was about 100 g/m3, and concentration grade III
      of mugwort pollen was distributed during the last ten days of August and the
      beginning of September.

PMID- 20128278
TI  - [Expression of STAT6 in human nasal polyps and the relation between STAT6 and
      eosinophil infiltration].
AB  - OBJECTIVE: To study the distribution and expression of STAT6 and to examine the
      suggested roles of STAT6 in the pathogenesis of eosinophil infiltration in nasal
      polyps and to evaluate the role of STAT6 in the pathogenesis of nasal polyps.
      METHOD: All selected cases met the enrollment criteria. Thirty samples of nasal
      polyps were obtained from patients undergoing nasal polypectomy, and 10 samples
      of inferior turbinate tissues were from patients undergoing nasal septal
      reconstruction. STAT6 in nasal polyp tissues from 30 nasal polyposis patients and
      10 samples of inferior turbinate tissues were detected with immunohistochemistry
      (SP) method. SPSS13.0 system was used to perform the statistical analysis.
      RESULT: The positive expression of STAT6 was significantly higher in epithelium
      of nasal polyps than that of the control. The number of eosinophils was
      significantly higher in epithelium of nasal polyps than that of the control. The
      difference between these two groups was statistically significant (P<0.05). STAT6
      positive cell were localized on epithelium, gland cells and on inflammatory cell
      of nasal polyps. STAT6 expression was positively correlated with the recruitment
      of eosinophils in nasal polyps. CONCLUSION: The high expression of STAT6 protein
      and the suggested roles of STAT6 in the recruitment of eosinophils in nasal
      polyps may contribute to the initiation and progression of nasal polyps.

PMID- 20128279
TI  - [Operation pathways for sphenoidal sinus by nasal endoscope and treatments for
      correlated diseases beyond scope of sphenoidal sinus].
AB  - OBJECTIVE: We probe more direct operation pathways in sphenoidal sinus and saddle
      area, and take proper measures for correlated diseases which surpass scope of
      sphenoidal sinus by combining image data, which could prevent serious
      complication. METHOD: Under nasal endoscope, the operation approaches we adopted
      included trans-anterior ethmoid sinus-posterior ethmoid sinus-sphenoidal sinus
      pathway, trans-meatus nasi superior-posterior ethmoid sinus-sphenoidal sinus
      pathway, trans nasal septum-sphenoidal sinus pathway and trans-natural opening of
      sphenoid sinus anterior into sphenoid sinus pathway by taking upper edge of
      posterior naris as a consistent surgical landmark. Forty-six cases who had
      sphenoidal sinus mass with bone erosion received surgical treatment. RESULT:
      Twenty-one cases with cyst and pus cyst of sphenoidal sinus had been healed by
      trans-meatus nasi superior pathway; 1 case with hematoma and organization in
      sphenoidal sinus had been cleared by trans-meatus nasi superior pathway; 3 cases
      had hematoma and organization in sphenoidal sinus and pseudoaneurysm in internal
      carotid artery, one of them suffered fatal hemorrhage in surgical exploration,
      and cured by endovascular embolization, the other two only underwent nasal
      endoscopic examination, the diagnosis was established by DSA and they received
      interventional therapy; 4 cases with papilloma in sphenoidal sinus had been
      treated by trans-natural opening of sphenoid sinus approach, and 3 cases were
      cured, 1 case had only partial mass resection as the papilloma offended the outer
      wall of sphenoidal sinus diffusely; 2 cases with cholesteatoma of sphenoid sinus
      have been removed completely by trans-meatus nasi superior approach; 1 case with
      encephalomeningocele of sphenoidal sinus underwent sphenoidotomy by trans-natural
      opening of anterior of sphenoidal sinus, and intraoperative puncture showed
      characteristic cerebrospinal fluid, the exposed meninges were then repair
      surgically; 1 case with mycosis of sphenoidal sinus had been cured by thorough
      clearing of the lesion in sphenoidal sinus combined with antifungal therapy; 3
      cases with malignancy of sphenoidal sinus had received major mass resection of
      sphenoidal sinus by trans-anterior ethmoid sinus-posterior ethmoid sinus
      approach, and followed with radio therapy and chemotherapy; 5 cases with NPC
      involving sphenoidal sinus had been treated by radio therapy and chemotherapy
      after pathological examination; 5 cases with post-operative cerebrospinal
      rhinorrhea and granulation hyperplasia of sphenoidal sinus had been repaired
      successfully by trans-meatus nasi superior approach or tans-nasal septum
      approach. CONCLUSION: There are various surgical pathways to deal with sphenoidal
      sinus and correlated diseases under nasal endoscope. The operation will be
      direct, safe and minimal invasive if we choose the pathway properly. Thin slice
      CT scan and 3D reconstruction of sella, and DSA or angiography of brain before
      operation is one of effective means to prevent surgical complications for lesions
      beyond scope of sphenoidal sinus.

PMID- 20128280
TI  - [The expression of mucins gene in the human nasal polyps and allergic rhinitis].
AB  - OBJECTIVE: To detect the mucin gene (MUC2, MUC5AC, MUC5B, MUC18 and MUC19)
      expression in the nasal polyps, allergic rhinitis (AR) and the normal nasal
      mucosa in human. To investigate the role and clinical significance of mucin gene
      in the pathogenesis of nasal polyps and AR patients. METHOD: We obtained samples
      from 35 cases of nasal polyps, 18 cases of AR inferior turbinate and 18 cases of
      simple nasal septum deviation inferior turbinate. Specimens were analyzed with RT
      PCR and Real-time FQ-RT-PCR. RESULT: The results of RT-PCR and FQ-RT-PCR showed
      that the expression of MUC5AC, MUC5B in nasal polyps and AR patients was
      significantly higher than that in normal mucosa (P<0.05). The expression of
      MUC5AC, MUC5B in nasal polyps was not significantly different from that in AR
      patients (P>0.05). The expression of MUC2, MUC18 in nasal polyps and AR was not
      significantly different from that in normal mucosa (P>0.05). And the results of
      RT-PCR for MUC19 expression in AR was higher than that in nasal polyps group and
      normal group (P<0.05 or P<0.01). CONCLUSION: MUC5AC and MUC5B are highly
      expressed in epithelium of human nasal polyps and AR, and they take part in mucus
      over-secretion in nasal polyps and AR. The expression of MUC19 in AR was higher
      than that in nasal polyps group and normal group. It indicates that the secretion
      of MUC19 in allergic rhinitis was on high level. There was no difference of the
      expression of MUC2 and MUC18 in nasal polyps group, AR group and in normal group.

PMID- 20128281
TI  - [Intranasal endoscopic repair of 15 cases of cerebrospinal fluid rhinorrhea].
AB  - OBJECTIVE: To summarize endoscopic management of cerebrospinal rhinorrhea and
      position-determining means. METHOD: Fifteen cases of cerebrospinal rhinorrhea
      treated by endoscopic approach at our institution were analyzed retrospectively.
      Aetiology included accidental trauma (10), surgical trauma (4), idiopathic (1).
      All patients presented with CSF rhinorrhea. Six cases were operated after failure
      of conservative treatment. Two cases after failure of neurosurgical repair were
      referred to our department. The largest defect was as big as 2.5 cm x 1.5 cm. All
      patients were scanned by computed tomography and magnetic resonance imaging and
      confirmed by biochemistry test. Ten patients received high resolution spiral
      computed tomography bonding ventriculography. RESULT: We performed intranasal
      endoscopic repair in all 15 patients. All repairs were successful at the first
      attempt with a mean follow up of 20 months. One patient had light headache
      postoperatively and relieved with conservative treatment. All defects of skull
      base detected by computed tomography and ventriculography were confirmed in the
      operation. CONCLUSION: Intranasal endoscopic repair of cerebrospinal rhinorrhea
      can be an effective method. High resolution spiral computed tomography scan
      combined with ventriculography is a precise position-determining means. With the
      advancement of instrument and operative skill, the scope of endoscopic repair
      will further extend.

PMID- 20128282
TI  - [The management of space-occupying lesion of middle skull base involving sphenoid
      sinus by transnasal endoscopic surgery].
AB  - OBJECTIVE: To investigate the diagnosis and therapy of space-occupying lesion of
      middle skull base involving sphenoid sinus. METHOD: A retrospective analysis was
      performed. Eighteen patients with extradural space-occupying lesion of middle
      skull base involving sphenoid sinus underwent transnasal endoscopic surgery.
      RESULT: One case of primary empty sella turcica was misdiagnosed as sphenoidal
      sinus cyst. One case of fibrous dysplasia and one case of meningioma were all
      misdiagnosed as mycotic sphenoiditis. Total rate of misdiagnosis was 16.7%. Among
      the 18 cases, 17 cases underwent complete resection of the lesion, and only 1
      case underwent major resection of the lesion. The amount of blood loss during
      surgery ranged between 100 ml and 2,500 ml. One case had bacterial meningitis
      which was cured after corresponding treatment. One case was blind in both eyes.
      And the other case died of pulmonary embolism. CONCLUSION: Transnasal endoscopic
      surgery is feasible and practical to treat benign space-occupying lesion of
      sphenoidal sinus and extradural lesion of middle skull base involving sphenoidal
      sinus. Definite diagnosis, accurate location and careful operation are important
      to complete the surgery successfully.

PMID- 20128283
TI  - [Expression of Survivin and Bcl-2 in sinonasal inverted papilloma].
AB  - OBJECTIVE: To investigate the expression of Survivin and its relationship with
      the expression of Bcl-2 in sinonasal inverted papilloma (SNIP). METHOD:
      Immunohistochemical method was used to determine the expression of Survivin and
      Bcl-2 in 30 cases of SNIP, 10 cases of sinonasal squamous cell carcinoma (SCC)
      and 10 cases of normal inferior concha tissues. RESULT: Survivin was expressed in
      22 of 30 (73.3%) cases of SNIP, 8 of 10 (80.0%) cases of SCC and not expressed in
      10 (0%) cases of normal inferior concha tissues. Expression of Survivin was
      significantly higher in SNIP and SCC than in normal tissues. Bcl-2 was expressed
      in 9 of 10 (90.0%) cases of SCC and 2 of 10 (20.0%) cases of normal inferior
      concha tissues. Expression of Bcl-2 was significantly higher in SCC than in
      normal tissues. Bcl-2 was expressed in 14 of 30 (46.7%) cases of SNIP, higher
      than normal tissues. Expression of Bcl-2 was positively related to expression of
      Survivin. CONCLUSION: Survivin may play an important role in the pathway of
      progression of SNIP and SCC. It may be identified as a new therapeutic target.
      Bcl-2 may play a synergic role with Survivin in progression of SNIP.

PMID- 20128284
TI  - [Effect of dexamethasone on post tonsillectomy pain].
AB  - OBJECTIVE: To assess the effect of a course of intravenous dexamethasone on pain
      after tonsillectomy. METHOD: Sixty patients who underwent tonsillectomy or
      adenoidectomy and tonsillectomy were randomly divided into experimental group and
      control group. Postoperatively, 30 patients in experimental group received anti
      inflammatory drug and dexamethasone for 4 days, and the other 30 patients in
      control group received anti-inflammatory drug and placebo. Degree of
      postoperative pain was measured with visual analogue scale in the patients more
      than 12-year-old and with Wong-Baker faces pain scale in the patients less than
      or equal to 12-year-old. The measurement was made twice daily for 5 days. RESULT:
      During the postoperative period, the scale value was decreasing every day in the
      all patients. But the value in experimental group was less than that in control
      group, and the difference was statistically significant (P<0.05). CONCLUSION:
      Dexamethasone given in this regime reduces postoperative pain and odynophagia
      after tonsillectomy.

PMID- 20128285
TI  - [Effect of intra nasally applied fluticasone propionate and levocabastine on the
      expression of aquaporin 5 in nasal mucosa of rat with experimental allergic
      rhinitis].
AB  - OBJECTIVE: To investigate the expression and distribution of aquaporin 5 (AQP5)
      in allergic rhinitis (AR) treated by fluticasone propionate and levocabastine.
      METHOD: Forty Wistar rats were divided randomly into AR (n=30) and control groups
      (n=10). After AR models were established, the AR rats were divided evenly into F
      group, L group and AR control group. Three groups were treated respectively for
      28 days, then the expression of AQP5 in nasal mucous membrane were detected by
      immunohistochemistry assay. RESULT: The distribution of AQP5 was consistent in
      all groups. The expression of AQP5 in F group was significantly different from L
      group and AR group (P<0.05), while there was no significant difference between
      that of AR group and L group (P>0.05). The expression of AQP5 in L group was
      significantly different from that in control group (P<0.05). CONCLUSION: High
      expressions of AQP5 in rat with AR indicated the positive correlation between
      AQP5 and AR. AQP5 might be one of pathological factors of AR concerned with
      glands excessive secretion and tissue edema. Glucocorticoid can down-regulate the
      expression of AQP5, but H1-receptor antagonist can not reduce the expression of
      AQP5.

PMID- 20128286
TI  - [Skin slice used as a model for investigating acupuncture effects].
AB  - OBJECTIVE: To establish an acupoint-connective tissue model for studying the
      mechanism of acupuncture by using in vitro patch clamp technique in the rat skin
      slices. METHODS: The local connective tissue under the corium of "Housanli" (ST
      36) area from SD rat was acutely and bluntly separated and fixed in a chamber
      filled with artificial incubation solution. Mast cells in the prepared connective
      tissue slice were labeled by toluidine blue (TB) or neutral red (NR). The whole
      cell current of mast cells responding to pressure stimulation applied through a
      patch pipette was recorded in rat slices derived from acupoint ST 36 area by
      using in vitro patch-clamp technique. RESULTS: 1) After staining with TB and NR,
      the labeled mast cells were found to distribute in the extracellular matrix of
      the connective tissue samples, and their degranulation phenomenon could be seen
      clearly. 2) The whole-cell current of mast cells in response to mechanical stress
      stimulation was successfully recorded in the connective tissue slices of the rat
      acupoint ST 36 area. The cellular membrane currents increased evidently when
      pressure gradients of -30, -60 or -90 cmH2O were applied to the recorded mast
      cells. CONCLUSION: The connective tissue slice from the rat ST 36 area may be
      used as a model for investigating the peripheral mechanism of acupuncture by
      combining the microtechniques and electrophysiological techniques. The results
      obtained in this model prove for the first time by electrophysiology that the
      mast cells in the connective tissue are probably involved in the transduction
      process of the mechanical signal from acupuncture stimulation. This new model
      provides a base for investigating the characters of the cells, collagen fibers,
      proteoglycans, etc. and their interactions in the acupoint connective tissue in
      the future.

PMID- 20128287
TI  - [Influence of electroacupuncture of meridian acupoints on the related hormones of
      the hypothalamus-pituitary-adrenal axis in rats with cerebral ischemia
      reperfusion injury].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the related
      hormones of the hypothalamus-pituitary-adrenal (HPA) axis in rats with cerebral
      ischemia-reperfusion injury (CI-RI). METHODS: Ninety Wistar rats were randomly
      divided into normal control, sham-operation (sham), model, EA acupoint and EA non
      acupoint groups. CI-RI model was established by using modified middle cerebral
      artery occlusion (MCAO) and reperfusion. These rats were further divided into 1
      day (d), 3 d and 7 d subgroups, with 6 cases in each. EA (1 mA, 2 Hz/30 Hz) was
      applied to acupoint "Zusanli" (ST 36) and "Quchi" (LI 11), and non-acupoints (5
      mm lateral to ST 36 and 5 mm apart from LI 11 on the radial side respectively)
      for 30 min, once daily for 1 d, 3 d and 7 d separately. Serum cortisole (CORT)
      content was assayed by enzyme linked immunosorbent assay (ELISA), and the
      expression of hypothalamic adrenocorticotropic releasing factor (CRF) mRNA and
      glucocorticoid receptor (GR) mRNA, and pituitary adrenocorticotrophic hormone
      (ACTH) mRNA was assayed by reverse transcription polymerase chain reaction (RT
      PCR) method. RESULTS: Compared with normal and sham groups, serum CORT levels of
      model and EA non-acupoint groups on the 1st, 3rd and 7th day increased
      significantly (P < 0.05), while compared with model groups, serum CORT level of
      EA acupoint groups decreased apparently (P < 0.05). Compared with normal and sham
      groups, hypothalamic CRF mRNA and pituitary ACTH mRNA expression of model groups
      were upregulated significantly on the 1st, 3rd and 7th d after CI-RI (P < 0.01, P
      < 0.05), and hypothalamic GR mRNA expression of model groups were obviously
      downregulated (P < 0.01, P < 0.05). In comparison with model groups, hypothalamic
      CRF mRNA and pituitary ACTH mRNA expression of EA acupoint groups at the 3 time
      points, and their expression of EA non-acupoint groups on the 1st and 3rd day
      were remarkably downregulated (P < 0.01, P < 0.05), and hypothalamic GR mRNA
      expression of EA acupoint groups was upregulated significantly at the 3 time
      points (P < 0.01, P < 0.05). Comparison between EA acupoint and EA non-acupoint
      groups showed that the effect of EA acupoint groups was obviously superior to
      that of EA non-acupoint groups in downregulating CRF mRNA and ACTH mRNA
      expression and in upregulating GR mRNA expression at the 3 time-points (P < 0.01,
      P < 0.05). CONCLUSION: EA of meridian-acupoints can effectively downregulate
      serum CORT content, hypothalamic CRF mRNA and pituitary ACTH mRNA expression and
      upregulate hypothalamic GR mRNA expression in CI-RI rats, which may contribute to
      its effect in relieving CI-RI.

PMID- 20128288
TI  - [Effect of scalp acupuncture on the expression of NF-kappaB mRNA, COX-2 mRNA and
      their proteins in rats with acute cerebral ischemia-reperfusion injury].
AB  - OBJECTIVE: To explore the possible mechanism of scalp acupuncture (SA) in
      relieving cerebral ischemia reperfusion (CI-R) injury. METHODS: Seventy male SD
      rats were randomized into sham-operation (sham, n = 10), model (n = 30) and SA (n
      = 30) groups. The later 2 groups were further divided into 24 h, 48 h and 72 h
      subgroups respectively, with 10 cases in each. CI-R model was established by
      middle cerebral artery occlusion (MCAO) and reperfusion. Electroacupuncture (2
      mA, 2 Hz/100 Hz) was applied to "Dingnie Houxiexian" (MS 7) and "Dingnie
      Qianxiexian" (MS 6) for 30 min, once every 24 h. Changes of the animal behavior
      were observed by using neurological severity score (NSS), nuclear factor-kappa B
      (NF-kappaB) and cyclooxygenase (COX-2) contents and their mRNA expression were
      detected with enzyme-linked immunosorbent assay (ELISA) and polymerase chain
      reaction (PCR) techniques respectively. RESULTS: Following modeling, the NSS at
      24 h, 48 h and 72 h after MCAO increased significantly, while compared with model
      group, NSS of SA group at the 3 time-points decreased considerably (P < 0.05, P <
      0.01), suggesting an improvement of the neurological functions after SA
      treatment. In comparison with sham group, NF-kappaB mRNA and COX-2 mRNA, and NF
      kappaB and COX-2 protein expression of model group in the infarcted cerebral
      tissue were significantly upregulated at the 3 time-points (P < 0.01) except NF
      KB mRNA at 72 h (no significant change), while compared with the 3 time-points of
      model group, NF-kappaB mRNA and COX-2 mRNA, and NF-KB and COX-2 protein
      expression of SA group were downregulated obviously (P < 0.01) except COX-2 mRNA
      at 72 h. CONCLUSION: Scalp acupuncture can suppress cerebral ischemia-induced
      upregulation of NF-kappaB mRNA and COX-2 mRNA, and NF-kappaB and COX-2 protein
      expression, which may contribute to its effect in promoting neurofunctional
      rehabilitation of CI-R rats by reducing cytokines-mediated inflammatory reaction.

PMID- 20128289
TI  - [Effect of electroacupuncture on the behavior and hippocampal ultrastructure in
      APP 695 V 717 I transgenic mice].
AB  - OBJECTIVE: To investigate the ultrastructural basis underlying electroacupuncture
      (EA) induced improvement of Alzheimer disease (AD) in transgenic mice. METHODS:
      Twelve APP 695 V 717 I transgenic mice were randomly divided into model group and
      EA group; and other 6 negative transgenic mice (C 57 BL/6 J) were made up of
      normal control group. After 3 months treatment by EA (15 min per other day, 2
      Hz/100 Hz, 3-4 mA) applied to "Baihui" (GV 20) and "Yongquan" (KI 1), the
      learning and memory ability of mice was measured by Lashley III water maze test,
      and the ultrastructural changes of hippocampal CA 1 region was observed by
      electronic microscopy. RESULTS: The swimming escape latency and the number of
      navigating errors (dead-end forward swimming) in model group were significantly
      longer and more than those in normal control group (P < 0.05); and those in EA
      group were considerably shorter and fewer than those in model group (P < 0.05),
      suggesting an improvement of learning-memory ability after EA. Comparison of the
      ultrastructure of the neurons in the hippocampal CA 1 region showed swelling of
      the mitochondria, broken or disappearance of the mitochondrial cristae,
      degeneration of the synapses, breakage and vague outline of the basement membrane
      of the blood capillaries in mice of model group; and basically distinct outline
      of the mitochondrial cristae and microvessels, and more synaptic vesicles in EA
      group. CONCLUSION: EA may effectively improve the learning-memory capacity of the
      APP transgenic AD mice and alleviate the pathological changes of neurons of the
      hippocampal CA 1 region, which may be one of the mechanisms underlying the
      improvement of AD by EA.

PMID- 20128290
TI  - [Study on the mechanism of electroacupuncture of different acupoint groups in the
      treatment of cerebrocardiac syndrome in rats].
AB  - OBJECTIVE: To compare the effects of electroacupuncture (EA) of different
      acupoint groups on heart rate variability (HRV) and cerebral glutamate (Glu) and
      aspartic acid (Asp) contents in cerebrocardiac syndrome (CCS) rats. METHODS: A
      total of 52 Wistar rats were randomized into normal (n = 8), sham-operation
      (sham, n = 8), model (n = 12), Shuigou-Fengfu (GV 26-GV 16, n = 12), and Neiguan
      Xinshu (PC 6-BL 15, n = 12) groups. CCS model was established by intracerebral
      (Caudate nucleus) injection of clostridiopeptidase (1 U/microl) plus heparin (7
      U/microl). EA (2 Hz/100 Hz, 1-3 mA) was applied to GV 26-GV 16 and PC 6-BL 15 for
      20 min, once daily for 3 days. Cerebral Glu and Asp contents were detected by
      high performance liquid chromatography, and HRV was analyzed by SMUP Software.
      RESULTS: In comparison with normal and sham groups, the R-R interval (RRI) of
      electrocardiogram and total variability (TV) of HRV, cerebral Glu and Asp
      contents in model group increased significantly (P < 0.01, P < 0.05), and the
      ratio of low frequency/high frequency (LF/HF) decreased evidently (P < 0.01).
      Compared with model group, RRI and TV values, and cerebral Glu and Asp contents
      of EA of GV 26-GV 16 and PC 6-BL 15 groups reduced markedly (P < 0.01, P < 0.05),
      LF/HF of the later two groups increased evidently (P < 0.01). No significant
      differences were found between GV 26-GV 16 and PC 6-BL 15 groups in RRI, TV and
      LF/HF of HRV, and cerebral Glu and Asp contents (P > 0.05). CONCLUSION: EA of
      both GV 26-GV 16 and PC 6-BL 15 can effectively improve CCS in rats, which is
      closely associated with their effects in lowering cerebral Glu and Asp levels and
      in suppressing the excitability of sympathetic nerve.

PMID- 20128291
TI  - [Observation on the analgesic effect of heat-reinforcing needling manipulation
      for acute arthritis and the concomitant changes of beta-EP and PGE2 contents in
      the local joint tissue in rabbits].
AB  - OBJECTIVE: To observe the analgesic effect of heat-reinforcing needling
      manipulation for acute inflammatory arthritis and its underlying mechanism in
      experimental rheumatoid arthritis rabbits. METHODS: A total of 60 rabbits were
      randomized into control (n=6), model (n=6), needle-twirling (n=24) and heat
      reinforcing (n=24) groups, and the later 2 groups were further divided into 0 h,
      0.5 h, 1 h and 2 h subgroups,with 6 cases in each. Rheumatoid arthritis model was
      established by injecting mixed solution of egg-albumin (4 mg/ml) and equal volume
      of complete Freund's adjuvant (CFA) into the subcutaneous tissue (6 points around
      the shoulder, 0.2 ml/point). Fourteen days later,the injection was repeated once
      again,and another 6 days later, egg-albumin (0.4 ml, 20 mg/ml) solution was
      injected into the bilateral knee-joints. "Zusanli" (ST 36) and "Hegu" (LI 4) were
      punctured and stimulated by needle-twirling or by heat-reinforcing needling
      technique for 1 min, with the needle retained for 30 min. The pain threshold of
      the paw was detected with K+ import stimulation method. beta-EP and PGE2 contents
      of the joint tissue were assayed with radioimmunoassay. RESULTS: Compared with
      model group, the pain threshold of needle-twirling group and heat-reinforcing
      group at each time-point increased significantly (P<0.01, P<0.05). Compared with
      needle-twirling group, the pain threshold of heat-reinforcing group at 0.5 h, 1 h
      and 2 h subgroups increased significantly (P<0.05, P<0.01). Both beta-EP and PGE2
      contents of model group were significantly higher than those of control group
      (P<0.01, P<0.05). In comparison with model group, beta-EP contents of needle
      twirling group and heat-reinforcing group at each time-point increased
      significantly (P<0.01, P<0.05), and PGE2 contents of needle-twirling group and
      heat-reinforcing group at each time-point decreased significantly (P<0.01,
      P<0.05). The beta-EP content of heat-reinforcing group was significantly higher
      than that of needle-twirling group at 2 h (P<0.05), while PGE2 content of the
      former group was significantly lower than that of needle-twirling group at 0 h
      (P<0.01). CONCLUSION: Both needle-twirling and heat-reinforcing needling can
      effectively raise the pain threshold in acute arthritis rabbits, which my be
      closely associated with their effects in upregulating beta-EP content and
      lowering PGE2 level in the local joint tissue. The analgesic effect of heat
      reinforcing needling manipulation is superior to that of needle-twirling.

PMID- 20128292
TI  - [Effects of electroacupuncture on long-term potentiation of synaptic transmission
      in spinal dorsal horn in rats with neuropathic pain].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Huantiao" (GB 30)
      and "Weizhong" (BL 40) on the mechanical pain threshold and the long-term
      potentiation (LTP) of the spinal dorsal horn in rats with neuropathic pain.
      METHODS: Thirty SD rats were randomized into control (sham-operation), model and
      electroacupuncture (EA) groups, with 10 cases in each. The neuropathic pain model
      was established by ligature and transaction of the popliteal nerve and common
      peroneal nerve. EA (2 Hz, 1 mA) was applied to "Huantiao" (GB 30) and "Weizhong"
      (BL 40) on the affected side for 30 min, once daily for 7 days. The mechanical
      pain threshold of the paw was detected before and after modeling and EA. LTP of C
      fiber stimulation (2 mA, 0.5 ms, 100 Hz, interval 10 s, 4 strains) evoked field
      potentials in spinal dorsal horn (L4/L5) was recorded in rats under anesthesia.
      RESULTS: Compared with control group, the pain threshold of model group reduced
      significantly from the 1st day on after ligature and transaction of the nerve
      (P<0.01), while 14 days after EA, it elevated evidently in comparison with model
      group (P<0.01), suggesting an increase of the mechanical pain threshold after EA.
      Comparison of the variance rates of C-fiber induced LTP of the field potential
      among the 3 groups showed that the variance rate of EA group was significantly
      lower than that of model group (P<0.01). Self-comparison of EA group showed that
      after EA, the variance rate of LTP reduced significantly (P<0.01). CONCLUSION: EA
      of "Huantiao" (GB 30) and "Weizhong" (BL 40) can significantly relieve
      neuropathic pain in rats with nerve injury, and inhibit C-fiber high-frequency
      stimulation induced LTP due to central sensitization induced abnormality synaptic
      transmission.

PMID- 20128293
TI  - [Effect of electroacupuncture combined with Ginkgo biloba extract (GBE 50) on
      learning-memory ability and hippocampal cytokine levels in rats with dysmnesy].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with Ginkgo
      biloba extract (GBE 50) on learning-memory ability and hippocampal cytokine
      contents in aging rats for exploring its underlying mechanism in the treatment of
      dysmnesy. METHODS: Forty-five SD rats were randomly divided into control (n=9),
      model (n=8), EA (n=10), GBE 50 (n=9) and EA + GBE 50 (n=9) groups. The dysmnesy
      model was established by D-galactose intraperitoneal injection for 42 days. EA (3
      Hz, 1 mA) was applied to "Baihui" (GV 20) and "Zusanli" (ST 36) for 20 min, once
      every other day for 21 days. The learning-memory ability was detected by Morris
      water maze tests. The levels of IL-1beta, IL-6 and TNF-alpha in hippocampus were
      examined by radioimmunoassay. RESULTS: Compared with control group, the mean
      escape latency (MEL) of the rats in model group was significantly greater on the
      2nd and 3rd day training (P<0.05, P<0.01), and the percent of swimming distance
      (PSD) in the target quadrant was shortened significantly (P<0.01). Compared with
      model group, the MEL values of the rats in EA, GBE 50 and EA + GBE 50 groups were
      significantly shortened (P<0.05, P<0.01), and the PSD values of the later 3
      groups increased considerably (P<0.01). Comparison among the EA, GBE 50 and EA +
      GBE 50 groups showed that the MEL of EA + GBE 50 was obviously shorter than those
      of EA and GBE 50 groups (P<0.05). Compared with control group, the contents of IL
      1beta) and TNF-alpha in hippocampus in model group increased significantly, but
      IL-6 decreased markedly (P<0.05, P<0.01). In comparison with model group, the IL
      1beta contents of EA, GBE 50 and EA + GBE 50 groups, and TNF-alpha of EA and EA +
      GBE 50 groups were reduced significantly (P<0.05, P<0.01); and the contents of IL
      6 in GBE 50 and EA + GBE 50 groups increased apparently (P<0.01). No significant
      differences were found between model and EA groups in IL-6 levels, and between
      model and EA + GBE 50 groups in hippocampal TNF-a levels (P>0.05). CONCLUSION:
      Both EA and GBE 50 can improve the dysmnesy rats' learning-memory ability, which
      may be closely associated with their effects in regulating hippocampal IL-1beta,
      IL-6 and TNF-alpha levels to relieve the inflammatory reaction. Combined
      administration of EA and GBE 50 has a synergic effect.

PMID- 20128294
TI  - [Effect of multiple paralleled acupuncture needles stimulation of scalp points on
      hemodynamics and blood flow energy of the common carotid artery in stroke
      patients].
AB  - OBJECTIVE: To observe the changes of carotid hemodynamic and hydraulic power
      indices after paralleled scalp-point acupuncture therapy in post-stroke patients.
      METHODS: Twenty post-stroke volunteer patients were enlisted in the present
      study. Aseptic filiform needles were inserted into Baihui (GV 20), bilateral
      Motor Area (MS 8), etc. with the needles retained for 5 min. The treatment was
      given one time. Hemodynamic indices: mean velocity of blood flow (Vmean), maximum
      velocity (Vmax), minimum velocity (Vmin), mean blood flow (Qmean), maximum blood
      flow (Qmax), minimum blood flow (Qmin), natural impedance (Zc), peripheral
      resistance (Rc), dynamic resistance (Dr), and critical pressure (Pc) before and
      after the treatment were detected with KF-3000 Brain Circulation Analyzer. The
      hydraulic power indices:stable potential energy (Ws), oscillation potential
      energy (Wo), total potential energy (Wc), stable kinetic energy (Ks), success
      kinetic energy (Ko), total kinetic energy (Kc), stable total energy (Ts),
      oscillation total energy (To), total energy (Tc), To/Tc, Kc/Tc, Wo/Wc and Ks/Kc
      were obtained through calculation. RESULTS: After the therapy, Vmin, Vmean, Qmin
      and Qmean increased significantly (P<0.001), while Rc decreased evidently
      (P<0.001). Ws, Ks, Ts, Wc, Kc, Tc and Kc/Tc increased obviously (P<0.001,
      P<0.05), and Ks/Kc declined significantly (P<0.01). The rest indices had no
      significant changes after the treatment. CONCLUSION: Multiple paralleled scalp
      acupuncture needles stimulation can effectively raise the blood flow volume of
      the common caroitid artery, leading to an increase of the energy supply of the
      cerebral blood circulation, but has no apparent influence on the total
      oscillatory energy/total energy in stroke patients.

PMID- 20128295
TI  - [Effects of electroacupuncture on bispectral index and plasma beta-endorphin in
      patients undergoing colonoscopy].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on bispectral index
      (BIS) and plasma beta-endorphin (beta-EP) level in patients undergoing
      colonoscopy. METHODS: Sixty patients were equally randomized into EA group and
      control group with 30 cases in each. EA (2 Hz/100 Hz, 4-6 V) was applied to the
      right Zusanli (ST 36) and Shangjuxu (ST 37), and the left Yinlingquan (SP 9),
      Sanyinjiao (SP 6) and bilateral Hegu (LI 4) respectively 30 min before
      colonoscopy. The mean arterial pressure (MAP), heart rate (HR) and BIS in two
      groups were continuously monitored during the study. Plasma beta-EP concentration
      was detected by radioimmunoassay. The patient's adverse reactions (including
      pain, satisfaction degree, etc.) were evaluated by visual analog scale (VAS) and
      verbal stress scale (VSS). RESULTS: Self-comparison showed that MAP and HR in
      control group increased significantly during colonoscope's splenic flexure
      passing (P<0.05). Whereas the 2 indexes in EA group had no significant changes
      during colonoscope insertion, and its splenic flexure passing, hepatic flexure
      passing and post-enteroscopy (P>0.05). Comparison between two groups showed that
      MAP at the time-point of colonoscope insertion, and HR at the time-point of
      colonoscope's splenic flexure passing in EA group were significantly lower than
      those in control group (P<0.05). BIS values of EA group were significantly lower
      than those of control group at different time-points after colonoscope insertion
      (P<0.01). Plasma beta-EP concentrations at the time-points of colonoscope's
      hepatic flexure passing and post-enteroscopy were evidently increased in both
      groups in comparison with pre-enteroscopy (P<0.01), and beta-EP was significantly
      lower in EA group than that in control group at the time-point of colonoscope's
      hepatic flexure passing (P<0.05). The dosage of Midazolam used for conscious
      sedation and the scores of VAS and VSS were also considerably lower in EA group
      than those in control group (P<0.05, P<0.01). No significant differences were
      found between two groups in the adverse reactions as dizziness, nausea, vomiting
      and abdominal pain, but the patients' satisfaction degree in EA group was
      evidently higher than that in control group (P<0.05). CONCLUSION: Acupuncture
      analgesia can effectively lower the colonoscopy patients' BIS value and plasma
      beta-EP level, meaning attenuation of the patients' stress responses during
      colonoscopy after EA.

PMID- 20128296
TI  - [Influence of needle-pricking bleeding combined with pulling-rotating
      manipulation on blood rheology in patients with vertebral artery type cervical
      spondylosis].
AB  - OBJECTIVE: To observe the effect of needle-pricking bleeding combined with
      pulling-rotating manipulation and simple manipulation on blood rheology in
      vertebral artery type cervical spondylosis (VATCS) patients, so as to analyze
      their mechanisms in relieving VATCS. METHODS: A total of 198 VATCS patients were
      randomly divided into treatment group (n=101) which was treated with needle
      pricking plus pulling-rotating manipulation, and control group (n=97) which was
      treated with simple pulling-rotating manipulation, according to the random number
      table. The treatment was given once every 7 days, 9 times altogether. The peak
      systolic blood flow velocity (Vpeak), end-diastolic blood velocity (Vmin),
      pulsatility index (PI) and resistent index (RI) of bilateral vertebral arteries
      (VA) and basilar artery (BA) were detected by transcranial doppler sonography
      (TCD). Whole blood apparent viscosity and the plasma viscosity in the treatment
      group were determined by using a blood viscosimeter. RESULTS: Of the 101 and 97
      VATCS cases in the treatment and control groups, 62 (61.38%) and 12 (12.37%) were
      cured basically, 23 (22.77%) and 26 (26.80%) experienced marked improvement, 14
      (13.86%) and 41 (42.27%) were improved. 2 (1.98%) and 18 (18.55%) failed in the
      treatment, with the total effective rates being 98.01% and 81.44% separately. The
      effective rate of the treatment group was significantly higher than that of
      control group (P<0.05). Compared with pretreatment, Vpeak and Vmin of the
      bilateral VA and BA in the treatment group, and Vpeak of the right VA in the
      control group increased significantly (P<0.01, P<0.05), PI and RI of the
      bilateral VA and BA in the treatment group, and PI and RI of the right VA in the
      control group decreased significantly (P<0.01, P<0.05), suggesting a marked
      reduction of the vascular resistance and an apparent increase of the cerebral
      blood supply after the treatment. The therapeutic effects of the above-mentioned
      indexes of treatment group were significantly superior to those of the control
      group (P<0.05). In comparison with pre-treatment, the whole blood apparent
      viscosity (high, medium and low shear rates) and plasma viscosity of the
      treatment group post-treatment were obviously reduced (P<0.01, P<0.05).
      CONCLUSION: Needle-pricking therapy combined with pulling-rotating manipulation
      can significantly improve VATCS patients' clinical symptoms, which may be closely
      related to its effects in lowering vascular blood resistance and blood viscosity
      and increasing cerebral blood supply.

PMID- 20128297
TI  - [Considerations about developing a clinical decision support system for evidence
      based diagnosis and treatment of acupuncture-moxibustion].
AB  - To develop a practical clinical decision support system (CDSS) for acu
      moxibustion therapy is of highly realistic significance in assisting
      acupuncturists with their decision-making tasks. In the present paper, the
      authors review the general state of studies on CDSS and analyze the extant
      problems and those needing to be tackled urgently in acu-moxibustion clinic.
      Secondly, the authors put forward some thoughts on developing CDSS for acu
      moxibustion and analyze its practicability. In conclusion, the authors think that
      by making full use of modern methodology of evidence-based medicine and utilizing
      the abundant available information of current databases and data mining
      techniques, to develop a practical CDSS for acu-moxibustion is necessary.

PMID- 20128298
TI  - [Progress of studies on acu-moxibustion stimulation-induced cellular
      transmembrane signal transduction of the target-organs].
AB  - Abundant research results have shown that multiple levels and links of cellular
      transmembrane signal transduction pathways in the target organs were involved in
      the efficacy of acupuncture. For instance, 1) various extra-cellular growth
      factors for initiating signal transduction by activating tyrosine protein kinase
      and non-receptor tyrosine kinase, 2) G protein-coupled protein kinase-second
      signal messengers, 3) ligands acting on intra-nuclear receptors to activate
      transduction pathway of nuclear transcription factors of the target genes, have
      been demonstrated in the favorable regulating process of acupuncture and
      moxibustion in different pathological animal models. In the present paper, the
      authors review the progress of studies on the abovementioned mechanism of acu
      moxibustion underlying improving some disorders as 1) pain, cerebral ischemia,
      and senile dementia, 2) inflammation and tumor, and 3) myocardial ischemia.
      Moreover, the authors also analyze the extant problems and make a prospect on the
      future studies about the cellular transmembrane signal transduction pathways
      involving the effects of acupuncture and moxibustion.

PMID- 20128299
TI  - A final word.

PMID- 20128301
TI  - Gearing up, gowning up and other issues with H1N1.

PMID- 20128300
TI  - Clinical practice corner. The H1N1 virus.

PMID- 20128302
TI  - Palliative Care Task Force introduces new resources.

PMID- 20128303
TI  - A year with the elephant.

PMID- 20128304
TI  - Flu season 101. Make sure all staff are vaccinated with seasonal flu vaccine.

PMID- 20128305
TI  - Neoplasms of the genital tract in a Vietnamese potbellied pig.
AB  - A 9-year-old, female potbellied pig showed loss of appetite and abdominal
      distension. After clinical examination and ultrasonography, a tumour was
      suspected. At laparotomy a large mass was present in the genital tract. Because
      the mass could not be excised, the pig was euthanized. Pathological examination
      revealed leiomyoma of the cervix and uterus wall in addition to multifocal
      adenocarcinomas of the uterus.

PMID- 20128307
TI  - [Making (him) pay].

PMID- 20128306
TI  - [An unusual roundworm (Toxocara vitulorum) infection in suckling calves].
AB  - A 2-month-old suckling calf had complaints of diarrhea and roundworms near the
      perineum. Faecal examination showed the presence of a high number of roundworm
      eggs of Toxocara vitulorum. The calf was a daughter of a Piemontese cow, born on
      the farm, but with a grandmother imported from France. This case describes the
      measures taken on the farm to prevent clinical problems and dissemination of the
      infection to other farms.

PMID- 20128308
TI  - [The dairy industry asks, but does not require yet...].

PMID- 20128309
TI  - [You are a cow if you play with antibiotics].

PMID- 20128310
TI  - [Thinking quality: an example from the clinic].

PMID- 20128311
TI  - [Breaking a paw].

PMID- 20128312
TI  - [Development course Young Veterinarians will start shortly].

PMID- 20128313
TI  - [OIE-conference about international education development].

PMID- 20128314
TI  - [GGL-congress 2009: 'Resistance'].

PMID- 20128315
TI  - [Senior veterinarians visited the pre-GGL-congress evening].

PMID- 20128316
TI  - Effectiveness of a baking soda toothpaste delivering calcium and phosphate in
      reducing dentinal hypersensitivity.
AB  - OBJECTIVE: The purpose of this controlled clinical trial was to determine the
      effectiveness and safety of a single-phase dentifrice that delivers calcium,
      phosphate, and fluoride to the tooth surface (Arm & Hammer Enamel Care for
      Sensitive Teeth toothpaste, United Kingdom) in reducing dentinal
      hypersensitivity. METHODS: Two-hundred and eight qualifying subjects were
      randomly assigned to either the Enamel Care dentifrice group or a control
      dentifrice group, and brushed twice daily with their assigned dentifrice for
      eight weeks. Pain/discomfort in response to a thermal stimulus was assessed at
      baseline, week 4, and week 8 using a Visual Analogue Scale (VAS; primary outcome
      variable) and the Schiff Thermal Sensitivity Scale (STSS; secondary outcome
      variable). After eight weeks, volunteers from the Enamel Care group were switched
      to the control dentifrice and participated in a second eight-week study to
      determine the degree of persistence of pain reduction. RESULTS: Both groups had
      statistically significant VAS score reductions from baseline at weeks 4 and 8,
      with mean VAS scores in the Enamel Care group decreasing by 45.6% at week 4 and
      61.1% at week 8 (p < 0.0001). Enamel Care was statistically significantly more
      effective than the control at weeks 4 and 8, with respective mean VAS reductions
      of 63% (p < 0.0001) and 33% (p = 0.0004) greater than the control. Consistent
      with the VAS score results, the Enamel Care group had respective statistically
      significant STSS score reductions of 77% and 58% greater than the control group
      (p < 0.0001). The reductions in dentinal hypersensitivity seen in the Enamel Care
      group at week 8 persisted for an additional eight weeks, during which the
      subjects discontinued use of Enamel Care and brushed with the control dentifrice.
      CONCLUSION: Enamel Care for Sensitive Teeth toothpaste (United Kingdom) is an
      effective dentifrice for the management of dentinal hypersensitivity, and its
      efficacy persists for a least eight weeks following discontinued product use.

PMID- 20128317
TI  - Effect of herbal, essential oil, and chlorhexidine mouthrinses on the composition
      of the subgingival microbiota and clinical periodontal parameters.
AB  - OBJECTIVE: The purpose of the present investigation was to determine if
      antimicrobial mouthrinses with different formulations could affect the
      composition of the subgingival microbiota and clinical parameters of adjacent
      tissues in periodontal maintenance subjects. METHODS: One-hundred and sixteen
      subjects, who had been treated for chronic periodontitis and were in a
      maintenance program, were randomly assigned one of four mouthrinses, to be used
      twice daily for three months. The mouthrinses were herbal 1, herbal 2, essential
      oil, and chlorhexidine. Clinical measurements and subgingival plaque samples were
      taken at baseline and at three months. Plaque samples were individually evaluated
      for 18 test species/taxa using checkerboard DNA-DNA hybridization. Significance
      of differences between baseline and three months for both microbiological and
      clinical parameters were determined using the Wilcoxon Signed Ranks test.
      Significance of difference among groups for change in clinical and
      microbiological parameters was determined using analysis of covariance (ANCOVA),
      adjusting for baseline values. RESULTS: Shifts in species proportions differed
      significantly for 9/18 test species/taxa among the four mouthrinse groups.
      Streptococcus and Capnocytophaga species were reduced most in the herbal rinse
      groups, while Veillonella parvula was reduced most in the essential oil and
      chlorhexidine groups. Actinomyces were also markedly reduced in the chlorhexidine
      group. Mean Plaque (PI) and Gingival Indices (GI) were reduced between baseline
      and three months in each group. Results emphasize that chlorhexidine (p < 0.001)
      and herbal (p < 0.05) rinses significantly reduced PI. Some subjects in each
      group responded better than others. CONCLUSION: All four mouthrinses tested
      produced shifts in the composition of subgingival microbiota, although the
      results differed among the groups. The observed microbial changes were
      accompanied by improvements in clinical parameters in the periodontal maintenance
      subjects.

PMID- 20128318
TI  - A comparative clinical study evaluating stain removal efficacy of a new
      sensitivity whitening dentifrice compared to commercially available whitening
      dentifrices.
AB  - OBJECTIVE: To assess the extrinsic stain removal efficacy of a new sensitivity
      dentifrice containing sodium tripolyphosphate (STP) to marketed whitening
      toothpastes after six weeks of product use. METHODS: This was a single-center,
      double-blind, stratified, six-week clinical study comparing the reduction in
      stain area and intensity of Sensodyne Extra Whitening to Crest Maximum Strength
      Sensitivity Protection Whitening plus Scope and Colgate Tartar Control Plus
      Whitening Mint dentifrice, as measured by MacPherson's Modification of the Lobene
      Stain Index (MMLSI) in a forced stain model. RESULTS: Two-hundred and ninety-five
      subjects completed the study. Tooth stain MMSLI scores showed significant
      differences between Sensodyne and Crest dentifrices in favor of Sensodyne for all
      surface sites (p = 0.014), and individually for facial (p = 0.023), lingual (p =
      0.027), and interproximal (p = 0.014) surfaces. No significant statistical
      differences between Sensodyne and Colgate dentifrices were observed for any of
      the surfaces. CONCLUSION: Results from this stain removal clinical study
      demonstrate significant extrinsic stain removal efficacy for all dentifrices
      relative to baseline. Significant differences between the two marketed
      sensitivity whitening dentifrices were demonstrated in favor of the new Sensodyne
      Sensitivity Whitening dentifrice.

PMID- 20128319
TI  - Effect of topical applications of a novel chlorhexidine-thymol varnish formula on
      mutans streptococci and caries development in occlusal fissures of permanent
      molars.
AB  - OBJECTIVE: To evaluate the effect of a new formula of a chlorhexidine-thymol
      varnish on mutans streptococci (MS) colonization and fissure caries development.
      METHODS: The study group consisted of 58 healthy adolescents (12-17 years old)
      undergoing orthodontic treatment with fixed appliances. A double-blind split
      mouth design was applied, and 116 pairs of molar teeth were randomly assigned to
      topical varnish applications with either the new Cervitec Plus or its predecessor
      Cervitec. Both varnishes contained 1% CHX and 1% thymol (CHX/T) as active
      ingredients, but differed with respect to adhesive properties. The varnishes were
      applied in the fissures at baseline, and then every sixth week throughout the 48
      week study period. Endpoints were MS colonization (CRT test) and occlusal laser
      fluorescence (LF, DIAGNOdent) recordings carried out regularly during follow-up.
      RESULTS: A significant reduction in the levels of MS in the fissures after the
      initial treatment was displayed with both varnishes (p < 0.05), and the levels
      remained consistently suppressed throughout the follow-up period. A non
      significant but clear tendency was noted in favor of the new formula after six
      and 12 weeks, with fewer teeth harboring high counts (> or = 10(5) CFU) of MS
      (6w:12% vs. 24%, 12w:16% vs. 26%). No new lesions were registered in any subject,
      and the mean LF recordings did not change significantly over time in the groups.
      CONCLUSION: There were no statistically significant differences between the CHX/T
      varnishes in terms of bacterial growth and caries prevention. For MS suppression,
      a tendency towards an initially superior effect was displayed with the new
      formula.

PMID- 20128320
TI  - Clinical stain removal efficacy of two dentifrices after one and two weeks of
      use.
AB  - OBJECTIVE: This investigation evaluated extrinsic stain removal efficacy after
      brushing for one and two weeks with a commercially available fluoride dentifrice
      relative to Colgate Total Advanced Clean, a new dentifrice formulated with dual
      phase silica. METHODS: At the baseline visit, one-hundred and forty-four adult
      subjects were stratified by Lobene Stain Index scores and randomized to two
      treatment groups using either Total Advanced Clean dentifrice (0.3% triclosan, 2%
      copolymer, dual phase silica) or a commercially available fluoride dentifrice,
      and instructed to brush twice daily. Tooth stain evaluations were conducted on
      stain area, stain intensity, and a composite score of both, after one and two
      weeks of dentifrice use. RESULTS: Baseline scores demonstrated no significant
      differences between the two treatment groups for all evaluated stain parameters
      (p > 0.05). At both the one- and two-week post-use evaluations, subjects brushing
      with Total Advanced Clean demonstrated significant reductions for all stain
      parameters versus the control (p < 0.05). The Total Advanced Clean group
      demonstrated mean reductions in stain intensity of 0.37 and 0.74 at the one- and
      two-week evaluations, respectively, versus the control group. Corresponding mean
      reductions in stain area for the Total Advanced Clean group versus the control
      were 0.12 and 0.24 at the one- and two-week evaluations, respectively. The two
      post-use evaluations also demonstrated significant reductions in stain composite
      scores for the subjects assigned Total Advanced Clean (p < 0.0001). CONCLUSION:
      In comparison to the control dentifrice, the results demonstrated significantly
      more stain removal following the use of Total Advanced Clean at each recall
      visit. Subjects assigned Total Advanced Clean demonstrated continued reductions
      in stains from baseline to one week, and from one week to two weeks.

PMID- 20128321
TI  - Clinical performance of a bioactive dental luting cement--a prospective clinical
      pilot study.
AB  - OBJECTIVE: To conduct a pilot study determining the clinical efficacy ofa new
      bioactive dental cement (Ceramir Crown & Bridge) for permanent cementation in
      fixed prosthodontics. The composition is a hybrid comprised of a calcium
      aluminate and a glass ionomer. METHODS: This study examined the performance of
      Ceramir Crown & Bridge after cementation of high-gold alloy and porcelain-fused
      to-metal (PFM) single crowns and bridges. A total of 38 crowns and bridge
      abutments were cemented in 17 patients; 31 were on vital, seven on non-vital
      teeth. Six were bridges with 14 abutment teeth (12 vital/two non-vital). One
      fixed splint comprising two abutment teeth was also included in the study.
      Preparation parameters were recorded, as well as working time, setting time,
      seating characteristics, and ease of cement removal. Baseline data were collected
      on dispensing, mixing, and handling of the cement; gingival inflammation index
      (GI), and a visual analog scale (VAS) and categorical assessment measured pre
      cementation sensitivity. Post-cementation parameters were post-cementation
      sensitivity, categorical and VAS, gingival tissue reaction, marginal integrity,
      and discoloration. A one-week post-op telephone call recorded subjectively the
      patients' comfort level. RESULTS: Working time (two minutes) and setting time
      (four minutes) were well within normal limits. Cement removal was determined to
      be very easy. Thirteen of 17 patients reported no post-cementation sensitivity
      after seven days; four reported a low-grade sensitivity. All 17 patients were
      seen for recall examinations at 30 days and six months. Of the four sensitivity
      cases, three were related to hyperocclusion, which disappeared spontaneously
      after adjustment. One case was due to post-cementation pressure from a three-unit
      bridge, which disappeared without intervention. After six months, no retentive
      failures were recorded, no sensitivity was subjectively reported, marginal
      integrity scored 38 alphas, one tooth had a 1 and two teeth a 0.5 GI score.
      Average VAS score for tooth sensitivity decreased from 7.63 mm at baseline to
      0.44 mm at the six-month recall. Average GI score for gingival inflammation
      decreased from 0.56 at baseline to 0.11 at the six-month recall. CONCLUSION:
      After six months, Ceramir Crown & Bridge performed favorably as a luting agent
      for permanent cementation.

PMID- 20128322
TI  - Skeletal issues and bone health in patients with cancer. Introduction.

PMID- 20128323
TI  - Bone biology and the role of the RANK ligand pathway.
AB  - Bone biology and the molecular basis of normal bone remodeling are important for
      understanding bone health, particularly for medical professionals who are
      treating patients with skeletal complications. Key factors in bone remodeling
      include RANK ligand, which stimulates bone resorption, and osteoprotegerin (OPG),
      which inhibits bone resorption. The ratio between these two factors regulates
      osteoclast formation and activity. An imbalance in the expression of RANK ligand
      and OPG is an underlying mechanism in cancer treatment-induced bone loss, in bone
      metastasis in patients with solid tumors, and in osteolysis in patients with
      multiple myeloma. In cancer-induced bone disease, for example, RANK ligand
      overwhelms the effects of OPG, leading to imbalanced bone remodeling and the
      "vicious cycle" of metastatic disease. Experimental therapeutics that target RANK
      ligand are increasingly being studied and have shown promise for decreasing tumor
      related bone disease.

PMID- 20128324
TI  - Early breast and prostate cancer and clinical outcomes (fracture).
AB  - Osteoporosis is a skeletal disorder characterized by low bone mass that is
      associated with increased risk of fracture. Nearly 40% of the 12 million cancer
      survivors in the United States were diagnosed with breast and prostate cancer.
      Therapy for these two diseases is not uncommonly associated with bone loss
      related to hormone-ablative therapy. In women, this includes the use of endocrine
      therapies and chemotherapy-related premature menopause. In men, hormone-ablative
      therapies include gonadotropin-releasing hormone analogs and bilateral
      orchiectomy. Fracture risk assessment includes bone mineral density determination
      in appropriate populations and integration of findings with identified risk
      factors. Strategies to prevent and treat bone loss include nonpharmacologic and
      pharmacologic interventions. In the former case, regular weight-bearing and
      muscle-strengthening exercise is encouraged along with smoking cessation,
      modulation of alcohol consumption, and fall prevention. Supplementation with
      calcium and vitamin D decreases fracture risk in subgroups. Pharmacologic
      interventions include use of oral or intravenous bisphosphonates, selective
      estrogen receptor modulators, and calcitonin. Estrogen/menopause hormone
      therapies are not recommended for use in breast cancer survivors related to
      potential influence on recurrence. Strategies for management of bone loss in
      breast and prostate cancer are outlined by guidelines from the American Society
      of Clinical Oncology and the National Comprehensive Cancer Network.

PMID- 20128325
TI  - Metastatic cancer in solid tumors and clinical outcome: skeletal-related events.
AB  - Metastasis to the bone represents a frequent complication of visceral cancers,
      most commonly in patients with advanced breast, prostate, and lung cancer. More
      than 50% of patients with advanced breast or prostate cancer have identifiable
      bone metastasis, and 30% to 40% of patients with non-small-cell lung cancer
      ultimately develop metastases to bone. Most tumors preferentially metastasize to
      the axial skeleton, targeting the vertebrae, pelvis, proximal ends of long bones,
      and skull. Skeletal complications as a result of these metastases are widely
      recognized to increase mortality and decrease quality of life--specifically the
      loss of mobility, independence, and social functioning of a patient. Advances in
      understanding the mechanisms of metastasis to bone, the resulting physiologic
      disturbances that take place, screening, diagnosis, and availability of better
      treatment options are advancing clinicians' abilities to combat this devastating
      problem.

PMID- 20128326
TI  - Bone disease in multiple myeloma.
AB  - Multiple myeloma is a uniformly fatal hematologic malignancy that results from
      the clonal expansion of plasma cells within the bone marrow. Skeletal-related
      complications affect nearly all patients with multiple myeloma and have a major
      impact on both patient morbidity and mortality. These complications most
      frequently include the development of osteolytic lesions that lead to severe bone
      pain, hypercalcemia, and pathologic fractures. Comprehensive skeletal imaging,
      using first plain radiographs and then more advanced modalities if necessary, is
      critical both at the time of diagnosis and throughout the course of therapy to
      assess the skeletal impact of the disease. The widespread use of intravenous
      bisphosphonate therapy has significantly improved the quality of life of myeloma
      patients by limiting the amount of osteolytic destruction that occurs.
      Bisphosphonate treatment, however, does not lead to repair of bone damage that
      has already occurred. The recent identification of multiple molecular targets
      with key roles in the osteolytic process has illuminated our understanding of
      myeloma bone disease, and may transform our future approaches to providing
      multiple myeloma patients with optimal skeletal care.

PMID- 20128327
TI  - Cranial strains and malocclusion VIII: palatal expansion.
AB  - Current techniques for palatal expansion are reviewed. Pre-treatment asymmetry of
      the palate and maxillary arch is shown to be almost universal and is not randomly
      distributed. The use of a symmetrical expansion appliance does not necessarily
      result in a symmetrical arch. ALF appliances provide a means of achieving
      orthopedic, symmetrical expansion of the palate by using very light force. This
      is demonstrated in seven subjects. It is argued that rapid palatal expansion is
      an inappropriate, potentially iatrogenic procedure which no longer has a place in
      the orthodontic armamentarium.

PMID- 20128329
TI  - Part III camouflage technique and Class III philosophy.

PMID- 20128328
TI  - Preventive orthodontics for the 5- to 7-year-old with the Nite-Guide technique.
AB  - This preventive orthodontic technique is applicable for the 5- to 7-year-old to
      prevent problems involving crowding, spacing, rotations, overbite, overjet, gummy
      smiles, Class II molar relations, and TMJ dysfunction from developing. The
      technique is based on accepted published research on the development of the
      dentition. Patients are typically started at 5 or 6 years of age and wear two
      preformed appliances only while sleeping. The active stage lasts about 2 years.
      The same appliance is used as a retainer until 12 years when the patient is
      dismissed About 75% to 80% do not require further orthodontics. The total
      procedure takes about 2 to 3 hours of total chair time.

PMID- 20128331
TI  - Tis the season to be grateful.

PMID- 20128330
TI  - The palatally impacted cuspid.

PMID- 20128332
TI  - Interpreting fear of falling in the elderly: what do we need to consider?
AB  - PURPOSE: Fear of falling (FF) is a serious problem in elderly. Available scales
      quantify FF by generating an aggregate total FF score disregarding the
      environment in which fear is expressed. This study examined the differences in
      psychosocial and physical characteristics and global functional capabilities
      between the elderly who experienced FF exclusively for activities usually
      performed in community environments and those who reported FF only for home-based
      activities. METHODS: Older participants (age > or = 65, n = 1155) enrolled in the
      InCHIANTI study completed the evaluation of FF, personal mastery, depression,
      cognition, social support, lower limb strength, grip strength, balance, timed
      repeated sit-to-stand performance, visual acuity, and contrast sensitivity.
      Functional capacity measures included walking speed, ADL and IADL disability,
      self-reported difficulty climbing steps without support and difficulty walking at
      least 400m. Only those who reported FF exclusively for activities usually
      performed in the community environment (n = 232) or in home environment (n = 110)
      were included in the analysis. RESULTS: Multivariate analysis of variance
      revealed that those who reported FF exclusively for home-based activities were
      significantly worse in psychosocial and physical characteristics measured
      (F(1,339) = 4.27; p < 0.01) and were also less able in all global functional
      capacity measures (p = 0.04 to < 0.01). CONCLUSIONS: There are significant
      characteristic and functional differences between the older persons who have FF
      performing community environment activities and those who express FF in home
      environment activities. The results strongly indicate the need to classify FF
      according to the environment or alternatively, to derive an aggregate score by
      appropriately weighting according to the environment, for valid interpretation of
      FF.

PMID- 20128333
TI  - The relationship between fatigue, aerobic fitness, and motor control in people
      with chronic stroke: a pilot study.
AB  - BACKGROUND: Fatigue is a commonly neglected issue despite the high incidence rate
      reported in people post-stroke. OBJECTIVE: To explore the relationship between
      fatigue, aerobic fitness, and motor control in people with chronic stroke.
      METHODS: Nine people post-stroke participated in this cross-sectional study (7
      females, mean age = 56.8 (11.8) years, range 47-73, time post-stroke = 47.6
      (51.2) months, range 11-140). Participants performed a six-minute-walk exercise
      in order to induce fatigue, followed immediately by a Fatigue Index (FI) scale to
      report fatigue at the moment. The distance walked (6MWD) was documented. On a
      separate visit, aerobic fitness was characterized by VO(2Peak) using a cycle
      ergometer. In addition, Fugl-Meyer (FM) test was administered to assess motor
      control of the hemiparetic side. Pearson Product Correlation Coefficient and
      multiple linear regression were used to analyze the relationships between FI,
      VO(2Peak) and FM. RESULTS: VO(2Peak) showed significant positive correlations
      with FM (r = .779, p = .013) and 6MWD (r = .726, p = .027). Fatigue index
      displayed significant negative correlations with VO(2Peak) (r = -.739, p = .023)
      and FM (r = -.873, p = .002), but not with 6MWD (r = -.620, p = .075). Using
      stepwise multiple regression, we found that that FM was an independent predictor
      of FI (p = .002) and explained 76.2% of variance in FI (R2 = .762). CONCLUSION:
      Our data suggests that motor control capability may be a good predictor of
      fatigue in people post-stroke. Fatigue is a complex phenomenon; a quantifiable
      measure that is sensitive to multiple components is needed in order to
      distinguish the nature of fatigue and its contributing factors.

PMID- 20128334
TI  - Reliability and validity of a clinical test of reaction time in older adults.
AB  - PURPOSE: Reaction time is an important indicator of neuromuscular status in older
      adults. A simple, portable, and inexpensive method of measuring reaction time is
      needed for use in geriatric clinical settings. The purpose of this study was to
      examine the reliability and validity of the response speed subtest of the
      Bruininks-Oseretsky Test of Motor Proficiency (BOT) as an indicator of reaction
      time in older adults. METHODS: A volunteer sample of 30 community-dwelling men
      and women over the age of 65 years performed the response speed subtest of the
      BOT and an electronic reaction time test during a single test session.
      Statistical analyses included calculation of the intraclass correlation
      coefficient (ICC) for reliability testing and the Pearson product-moment
      correlation coefficient (r) for validity testing. RESULTS: Intertester
      reliability for the BOT response speed subtest using either mean or median scores
      for 7 test trials for each subject was ICC[2,1] = 0.99. Test-retest reliability
      for the BOT was ICC [2,1] = 0.53 using mean scores and ICC[2,1] = 0.65 using
      median scores. Mean scores from both the first and second administrations of the
      BOT subtest were correlated with electronic reaction time test scores (r = -0.41
      and r = -0.45, respectively; P < .05). Scores improved significantly from the
      first to the second test administration. CONCLUSIONS: Although intertester
      reliability was excellent, test-retest reliability for the BOT response speed
      subtest was not in an acceptable range for this sample of community-dwelling
      older adults. Further study of optimal methods of administration is needed to
      develop this measure for use in screening and examination of older adults.

PMID- 20128335
TI  - Can stimulating massage improve joint repositioning error in patients with knee
      osteoarthritis?
AB  - PURPOSE: The purpose of this study was to investigate the effect of massage
      applied to the thigh muscles on joint repositioning error (JRE) in patients
      suffering from osteoarthritis (OA).We hypothesized that stimulating massage of
      the muscles around an osteoarthritic knee joint, could improve the neuromuscular
      function and thereby optimize the positive and minimize the negative performance
      factors in relation to an exercise program. METHODS: In a cross-over design, 19
      patients with knee osteoarthritis, mean age of 73.1 years (SD: 9.4; range 56 to
      88 years), recruited from the local department of rheumatology, were randomly
      allocated to either receive massage and a week later, act as controls or vice
      versa. The applied massage consisted of stimulating massage of the quadriceps
      femoris, sartorious, gracilus, and hamstrings muscles for 10 min on the affected
      leg. Participants had their JRE measured before and immediately after the 10 min
      massage and control sessions. Data were analyzed by using paired t-test. RESULTS:
      No significant change in JRE was observed (95% CI: -0.62 degrees to 0.85 degrees,
      p = 0.738). CONCLUSION: Massage has no effect on the immediate joint
      repositioning error in patients with knee osteoarthritis, ie, if an improved JRE
      is important for improving the performance factors when exercising, stimulating
      massage may not be recommendable to use.

PMID- 20128336
TI  - Strength training improves submaximum cardiovascular performance in older men.
AB  - PURPOSE: To determine if 16 weeks of strength training can improve the
      cardiovascular function of older men during submaximum aerobic exercise. METHODS:
      Twenty four men aged 70-80 yr were randomly assigned to a strength training (ST;
      n = 12) and control group (C; n = 12). Training consisted of 3 sets of 6 - 10
      repetitions at 70% to 90% of 1RM, 3 times per week, on an incline squat machine
      for 16 weeks, followed by 4 weeks detraining. Leg strength and maximum oxygen
      consumption (VO2 max) were assessed every 4 weeks of the 20-week study.
      Cardiovascular function was assessed during submaximum cycle exercise at 40
      Watts, 50% and 70% of VO2 max before training, after 16 weeks training, and after
      4 weeks detraining. RESULTS: At 40 Watts, heart rate (HR), systolic blood
      pressure, and rate pressure product (RPP) were lower and stroke volume (SV)
      significantly higher after 16 weeks training and 4 weeks detraining: at 50% VO2
      max, HR and RPP were lower after 16 weeks training and 4 weeks detraining: at 70%
      VO2 max, cycle ergometry power, VO2 and arterio-venous oxygen difference (a - vO2
      ) were higher after 16 weeks training. Leg strength and VO2 max increased after
      16 weeks training, with leg strength remaining above pre-training levels after 4
      weeks detraining. CONCLUSIONS: Sixteen weeks of strength training significantly
      improves the cardiovascular function of older men. Therefore strength training
      not only increases muscular strength and hypertrophy but also provides
      significant cardiovascular benefits for older individuals.

PMID- 20128337
TI  - Multifactorial intervention with balance training as a core component among fall
      prone older adults.
AB  - PURPOSE: The purpose of this randomized controlled trial was to measure the
      effectiveness of A Matter of Balance, a small-group based balance program, on
      muscle strength, gait, balance, and fall risk among older community-dwelling
      adults at risk for falls. A secondary aim was to measure the effects of the
      program on actual fall rates over the 3-month study. METHODS: Twenty-three older
      adults were randomly assigned to either an experimental group that participated
      in a 12-week small-group based balance program or a control group. Subjects were
      assessed at baseline and following an intervention using the following outcome
      measures: lower extremity manual muscle testing (MMT) and range of motion; gait
      analysis on the GAITRite system; balance parameters on the SMART EquiTest, the
      Timed Up and Go test, the Berg Balance Scale, and incidence of falls. RESULTS: A
      repeated measures ANOVA revealed that there was a significant interaction between
      groups over time in the Berg Balance Scale scores, P < or = .05. The experimental
      group improved over time (48.1 to 52.9/56, respectively), whereas the control
      group decreased in performance (49.1 to 47.8/56, respectively), P < or = .05. The
      mean number of falls was significantly less in the experimental group during the
      intervention compared with the control group (0.09 and 0.50, respectively), P <
      or = .05. CONCLUSIONS: A community-based multifactorial intervention including
      individualized fall risk assessment, exercise, and home assessment appears to
      safely and effectively reduce the number of falls, resulting in significant
      improvements in functional balance ability and decreased fall risk.

PMID- 20128338
TI  - The effects of whole-body vibration training in aging adults: a systematic
      review.
AB  - BACKGROUND AND PURPOSE: Whole-body vibration (WBV), has become increasingly
      popular as a form of exercise training. WBV involves the application of a
      vibratory stimulus to the entire body as opposed to local stimulation of specific
      muscle groups. The purpose of this review was to assess the evidence concerning
      the effectiveness of WBV training studies on bone density, muscle performance,
      balance, and functional mobility in older adults and to discuss potential
      precautions, safety concerns, and practical clinical considerations of WBV.
      METHODS: A literature search of online databases was conducted and methodological
      quality assessment was performed using the critical appraisal scales developed by
      Sackett and Jadad on the WBV articles that met the predetermined inclusion
      criteria. RESULTS: The initial search resulted in the retrieval of 196 potential
      articles. One additional article was found by manual search. After review, 13
      studies were identified that met the predetermined selection criteria.
      DISCUSSION: Much of the WBV research to date is methodologically weak and should
      be interpreted with caution. Study protocols have used widely variable WBV
      parameters which also complicates the studies' interpretation. Some but not all
      of the studies in this review reported similar improvements in muscle
      performance, balance, and functional mobility with WBV as compared to traditional
      exercise programs. Bone studies consistently showed that WBV improved bone
      density in the hip and tibia but not in the lumbar spine. CONCLUSION: Additional
      studies are needed to determine safe and effective parameters for WBV training in
      older adults.

PMID- 20128339
TI  - The H1N1 virus: what's the problem?

PMID- 20128340
TI  - Protection from wrongful termination action.

PMID- 20128341
TI  - Therapy of rabies encephalitis.

PMID- 20128342
TI  - [Endocarditis due to infection by Paecilomyces variotii].
AB  - Fungal endocarditis is a cardiac complication that has been increasing throughout
      the world. We present a case of infective endocarditis by Paecilomyces variotii
      in a male patient with a prosthetic mitral valve. Successful treatment consisted
      of administration of amphotericin B (total dose 3670 mg) and mitral valve
      replacement. Only six cases have been reported previously, with a 100% mortality
      rate.

PMID- 20128343
TI  - [Allergy and intolerance to nonsteroidal antinflammatory drugs: successful
      desensitization in three cases].
AB  - Adverse reactions to nonsteroidal antinflammatory drugs are the second cause of
      reactions to drugs after beta-lactams. Prevalence of these reactions among
      general population is between 0.1-0.3%, and prevalence of nonsteroidal
      antinflammatory drug-induced anaphylaxis is 0.01%. Acetylsalicylic acid or
      nonsteroidal antinflammatory drug sensitivity can be manifested as acute
      urticaria, angioedema, acute asthma, acetylsalicylic acid exacerbated respiratory
      disease and anaphylaxis. An updated review based on three cases of patientes with
      acetylsalicylic acid or nonsteroidal antinflammatory drug intolerance is
      presented in which, because of their concomitant diseases, permanent treatment
      with acetylsalicylic acid was required. After undergoing a fast acetylsalicylic
      acid desentization protocol in an intensive care unit, these patients were able
      to receive daily acetylsalicylic acid doses without any adverse effects.

PMID- 20128344
TI  - [Human rabies encephalitis by a vampire bat bite in an urban area of Colombia].
AB  - Human rabies encephalitis by a vampire bat bite in an urban area of Colombia A
      case of rabies encephalitis is presented in a teenaged male, which developed four
      months after a bat bite in the urban area of Floridablanca, Santander Province,
      Colombia. The complex clinical manifestations prevented the confirmation of an
      antemortem diagnosis, principally because of the lengthy incubation period and
      the absence of other similar urban cases. Despite application of several
      therapies, including the Milwaukee protocol, the patient died 19 days after
      hospital admission. The autopsy revealed a necrotic, acute, pan-encephalitis of
      rabies virus etiology. The test of direct immunofluorescence in brain tissue was
      positive, as well as the biologic test in mice. Serological tests indicated it to
      be an antigenic variant type 3, whose main reservoir is the hematophagous vampire
      bat, Desmodus rotundus. This is probably the first case of bat-induced rabies
      reported in an urban community of Colombia and one of the few in Latin America.
      Although rabies encephalitis by a bat bite is rare, the case serves as a notice
      to health authorities and to the medical community to be alert to this risk.

PMID- 20128345
TI  - [An anatomical variation: the aberrant termination of the thoracic duct].
AB  - In a male cadaver dissected at the Department of Morphology, University del
      Valle, Call (Colombia), a rarely described anatomical variation was found. It
      consisted of an aberrant termination or drainage of the thoracic lymph duct.
      Normally, this duct ascends in the thorax behind the esophagus, gradually
      diverges towards the left side of the neck and ends in the left jugulo-subclavian
      confluent--either in the internal jugular vein or in the subclavian vein. In the
      case of this cadaver, the thoracic duct diverged towards the right side of the
      neck to end in the right internal jugular vein. The present work describes the
      embryonic origin of the duct and offers a possible explanation for the anatomical
      variation encountered.

PMID- 20128346
TI  - [Phylogenetic analysis indicates human origin of rotavirus and hepatitis A virus
      strains found in the drinking water of western Colombia].
AB  - INTRODUCTION: Quibdo, the capital of Choco Province, is one of the poorest cities
      in Colombia. Enteric viruses such as rotavirus and hepatitis A virus was found to
      occur commonly in city drinking water and indicated poor water quality and high
      risk of becoming infected. The source of these viruses was unknown, but humans
      and cattle were suspect sources. OBJECTIVE: City water was assessed to determine
      source and persistence of diarrhea and hepatitis among the human populations in
      the environs of Quibdo. MATERIAL AND METHODS: Four thousand liters of water were
      collected, filtered by tangential ultrafiltration and centrifuged in Centriprep
      Ultracel YM-50 tubes. Sixty samples of untreated and 20 of treated water were
      probed by RT-PCR. RESULTS: Six samples were positive for rotavirus and 2 for
      hepatitis A virus in both, treated and non treated water. DNA sequence analysis
      identified the presence of human G2 rotavirus and human hepatitis A virus.
      CONCLUSION: The evidence indicated a high level of contamination with pathogenic
      viruses in consumable water sources in Quibdo, Colombia.

PMID- 20128347
TI  - [Clonal expansion and genomic characterization of the human T-cell lymphotropic
      virus type I during the integration process in adult T-cell leukemia/lymphoma].
AB  - INTRODUCTION: Although the integration of human T-cell lymphotropic virus type I
      into the T-cells is not a random process, the mechanistic details are not
      understood. OBJECTIVES: The characteristics of the flanking host chromatin were
      evaluated at the integration sites in adult T-cell leukaemia/lymphoma (ATLL)
      patients infected with the virus. MATERIALS AND METHODS: From seven leukemic
      Colombian patients positive for the human T-cell lymphotropic virus type I (HTLV
      I), lymphocyte DNA samples were extracted and amplified by inverse polymerase
      chain reaction (IPCR). Clonal expansion and human genome nucleotide composition
      in an extension of 50 bp was determined. To establish the characteristics of the
      human genome flanking provirus, 61 IPCR sequences from Colombian and Japanese
      ATLL patients, were analyzed in silico to obtain insights about the genomic
      structure, functions and nature of associated chromatin. RESULTS: The clonal
      expansion of cell clones was predominantly oligoclonal. From 61 IPCR sequences,
      155 alignments with homology higher than 95% (e-value < 0.05) were screened.
      Seventy-five percent of those sequences corresponded to non coding elements that
      include repetitive and non-repetitive DNA. Fifty percent of the proviral
      integrations were associated with chromosomes of A and B groups. Viral DNA
      integration tended to favor exons of genes that replicated early, controlled the
      cell cycle, or were involved in signal transduction. CONCLUSIONS: The results
      indicated that HTLV-I integration was preferentially directed towards genomic
      environments with high C:G content, and toward genes that replicate early,
      regulate cell cycle or involved with signal transduction.

PMID- 20128348
TI  - [Seroprevalence of hepatitis B virus and human immunodeficiency virus infection
      in a population of multiply-transfused patients in Colombia].
AB  - INTRODUCTION: Although the transfusion of blood products is a common therapy, it
      carries risk of transmission of infections, especially hepatitus B virus (HBV)
      and human immunodeficiency virus (HIV). OBJECTIVE: As part of the blood safety
      initiative, the Pan American Health Organization supported studies to estimate
      the prevalence of human immunodeficiency virus and hepatitis B virus infection in
      Colombia. MATERIALS AND METHODS: Between February and September 2003, a cross
      sectional study examined 500 multiply-transfused patients at four hospital
      centers in the cities of Bogota and Medellin. The serum samples were analyzed by
      enzyme immunoassay (EIA) using commercial kits. RESULTS: The seroprevalence of
      HIV infection was 1.8% (CI 95% 0.5-3.1). The seroprevalence of HBV infection was
      18.6% (CI 95% 15.1-22.1). Six risk factors were associated with HIV and HBV
      infection: (1) receiving more than 48 units of blood or blood components, (2)
      diagnosis of hemophilia, (3) receiving transfusions for more than one year, (4)
      receiving whole blood, (5) coinfection with hepatitis C virus and (6) receiving
      transfusions before 1993. CONCLUSIONS: This is the first epidemiological study
      with a significant sample size performed in multiply-transfused patients in
      Colombia. The principal finding was the high prevalence of HBV and HIV infection
      in patients with diagnosis of hemophilia compared with the other five groups of
      multiply-transfused patients.

PMID- 20128349
TI  - [Development and validation of a multiplex polymerase chain reaction for
      molecular identification of Salmonella enterica serogroups B, C2, D and E].
AB  - INTRODUCTION: The scheme Kauffman-White (KW) for serotyping of Salmonella
      recognizes 46 O antigens, and 119 H antigens, thereby permitting the
      characterization of 2541 serotypes. The serotyping is a useful epidemiological
      tool in identifying circulating serotypes and to characterize outbreaks. However,
      the method presents technical limitations, difficulty in interpretation of
      results and high costs. OBJECTIVE: A multiplex polymerase chain reaction test (M
      PCR) was developed as an alternative method for the identification of serogroups
      B, C2, D, and E of Salmonella enterica. MATERIALS AND METHODS: The M-PCR detected
      Salmonella genes rfbJ of serogroups B and C2 and wzx of serogroups D and E. To
      standardize the M-PCR, reference strains of Salmonella serogroups were compared.
      Amplification of invA gender-specific gene of Salmonella was included as internal
      control of amplification. To validate the test, a blind study was conducted to
      identify by M-PCR 400 isolates that had been previously characterized by
      serology. RESULTS: The M-PCR detected Salmonella serogroups with reproducible
      results (Kappa index = 0.95). The sensitivity of the test was between 98% to 100%
      and specificity between 96% to 100%. CONCLUSIONS: The polymorphisms in the
      Salmonella genes rfbJ and wzx permitted the development of a method for molecular
      typing of Salmonella serogroups that was sensitive, specific and reproducible.

PMID- 20128350
TI  - [Risk factors associated with the presence of pneumonia in patients with brain
      injury].
AB  - INTRODUCTION: Pneumonia in patients with head trauma occurs commonly; however,
      few data are available to evaluate the effects of the infection on the prognosis.
      OBJECTIVE: The incidence and microbiological findings were described, and the
      associated risk factors were established with the appearance of pneumonia in
      patients with severe brain trauma. MATERIALS AND METHODS: A prospective cohort
      study was conducted that included 39 patients with severe brain trauma and who
      required mechanical ventilation; initially, none had pneumonia. These patients
      were observed during a 24-month period in an attempt to discern the principal
      risk factors associated with the onset of pneumonia. RESULTS: Pneumonia occurred
      in 31 (80%) of the 39 patients, and 28 of these presented early pneumonia. The
      most frequent germ in patients with pneumonia was Staphylococcus aureus with a
      percentage of the 42.4%. In the multivariate analysis, the single statistically
      significant risk factor was the presence of hypotension and vasopressor support
      with a RR = 27.9 (95% CI = 1.0-749.9, p < 0.05). No significant differences in
      the days of mechanical ventilation or mortality in both groups. The major
      mortality-associated risk factor in patients with pneumonia was a low Glasgow
      score at admittance with an OR = 2.19 (95% CI 1.03 - 4.65), p < 0.05.
      CONCLUSIONS: The incidence of pneumonia in patients with severe brain trauma is
      high; however, its appearance does not affect the prognosis. The single
      significant risk factor was the presence of hypotension and vasopressor support.

PMID- 20128351
TI  - [Validity and reliability of the Center for Epidemiologic Studies-Depression
      scale in Colombian adolescent students].
AB  - INTRODUCTION: Major depressive disorder is the second major cause of adolescent
      psychological incapacitation in Latin-America. However, scales for detecting
      these disorders have not been validated for screening adolescents in Colombia.
      OBJECTIVE: The validity and reliability of a Spanish translation of the Center
      for Epidemiologic Studies (CES-D)-Depression scale was assessed in adolescent
      students. MATERIALS AND METHODS: A validation study for a diagnostic scale was
      performed with a sample of 390 adolescent students from Bucaramanga, Santander
      Province, in northwestern Colombia. The students were evaluated by two methods:
      (a) the CPS-depression scale and (b) a semi-structured clinical interview. Three
      to 28 days after the interview, the scale was re-applied. Criterion validity,
      internal consistency and test-retest reliability was analyzed. RESULTS: The mean
      age was 14.8 +/- 1.2 years old. The prevalence of major depressive disorder was
      11.5%. Cronbach's alpha was 0.85. The area under the curve produced by the
      receiver operating characteristic curve was 0.82, and the cut point of > or =23
      showed a sensitivity of 73.3%; specificity, 73.6%; positive predictive value,
      26.6%, and negative predictive value, 95.5%. Lin's coefficient of concordance was
      0.75. CONCLUSIONS: The validity and reliability of the Spanish translation of the
      CES-D scale were similar to those reported in the international literature
      although with a higher cut point. CONCLUSIONS: The validity and reliability of
      the Spanish translation of the CES-D scale were similar to those reported in the
      international literature although with a higher cut point.

PMID- 20128352
TI  - [Changes in retinol, hemoglobin and ferritin concentrations in Colombian children
      with malaria].
AB  - INTRODUCTION: Malaria, anemia and intestinal parasitism can co-exist in certain
      populations of Colombian children. The effects of retinol supplementation and
      anti-intestinal parasite treatment in children with malaria is unknown. Changes
      after this treatment of with respect to hemoglobin, retinol, ferritin and C
      reactive protein levels have not been previously monitored. OBJECTIVE: The effect
      of simultaneous intervention with antimalarial, retinol supplementation and anti
      intestinal parasites treatment will be monitored by examining levels of
      hemoglobin, ferritin, retinol and C reactive protein in children with malaria.
      MATERIALS AND METHODS: A non-blind experimental study was conducted in 93
      children with malaria, aged 4-10 years. Each was randomly allocated to one of the
      following groups: (1) treatment with antimalarial and retinol supplement (Group
      MA); (2) treatment with antimalarialretinol supplement and anti-parasitic drug
      (Group MAP); (3) treatment with antimalarial and antiparasitic drug (Group MP),
      and (4) treatment only with antimalarials (Group M). The groups were observed for
      30 days, with haemoglobin, ferritin, retinol and C reactive protein evaluated on
      days 0, 8 and 30 after treatment. RESULTS: Mean values for the children at day 0
      were as follows: hemoglobin 10.3 +/- 1.6 g/dL, retinol 19.1 +/- 6.0 microg/dL, C
      reactive protein 75 +/- 63 mg/L and ferritin 213 +/- 203 microg/L. On day 30
      after treatment, hemoglobin and plasma retinol concentrations increased in 1.4 +/
      1.4 g/dL and 11.5 +/- 8.1 microg/dL, whereas the C reactive protein and ferritin
      concentrations decreased to 66 +/- 60 mg/L, and 184 +/- 203 microg/L,
      respectively. No statistically significant differences appeared among the groups.
      On day 8, significant differences between the groups were observed in hemoglobin
      concentrations Group MAP was higher when compared to other groups. CONCLUSION: On
      day 30, hemoglobin and retinol were high, whereas C reactive protein was low.
      Simultaneous administration of a retinol supplement and anti-parasite treatment
      prevented hemoglobin reduction observed on day 8 without changes in other
      variables.

PMID- 20128353
TI  - Evaluation of community-based strategies for Aedes aegypti control inside houses.
AB  - INTRODUCTION: Dengue viruses transmitted principally by the urban mosquito Aedes
      aegypti, cause one of the major public health problems confronting tropical
      cities. Insecticide spraying has been the mainstay of mosquito control; however,
      its continuous use has selected for resistance. Other important methods of
      control involve community participation. OBJECTIVE: This study evaluated two
      control methods for Ae. aegypti that can be used by the community: Lethal
      ovitraps (LOs) and Bacillus thuringiensis var israeliensis (Bti) briquettes.
      MATERIALS AND METHODS: The project study was carried out in four similar
      neighborhoods within a representative district in the city of Cali, Colombia.
      Three interventions (LO, Bti, LO+Bti plus education and one control (education
      only) area were evaluated for efficacy in post-intervention entomological
      surveys. Additionally, entomological indices were also compared to results from a
      pre-intervention survey carried out on a sample of city blocks in the same
      neighborhoods. Relative vector abundance in relation to weather conditions using
      the same entomological sampling methods was compared. RESULTS: The interventions
      did not achieve significant differences in vector abundance among the treatments.
      However, the interventions achieved a significant reduction in entomological
      indices compared with those observed during the pre-intervention survey: House
      index 15.1% vs. 8.5%, mean pupae per house 1.15 vs. 0.073, and Adult index 56.3%
      vs. 34.8% (p < 0.05). CONCLUSIONS: The lack of significant differences among the
      interventions, and between treated and control blocks suggested that educational
      activities together with periodic visits to the houses produced similar
      reductions of immature and adult Aedes aegypti.

PMID- 20128354
TI  - Distribution of Porphyromonas gingivalis fimA genotypes in isolates from
      subgingival plaque and blood sample during bacteremia.
AB  - INTRODUCTION: Porphyromonas gingivalis is considered as a major etiological agent
      in the onset and progression of chronic destructive periodontitis. Porphyromonus
      gingivalis fimA type has been correlated to the virulence potential of the
      strain; therefore this gene could be involved in the ability of P. gingivalis to
      reach blood stream. OBJECTIVE: The classifications of P. gingivalis fimA types
      will be compared in subgingival plaque and blood samples collected after scaling
      and root root planing of periodontitis patients. MATERIALS AND METHODS: Fifteen
      periodontitis patients requiring scaling and root planing were enrolled. P.
      gingivalis isolates were classed to genotype with fimA type-specific PCR assay.
      fimA gene was sequenced if the isolate was listed as unclassifiable after PCR
      technique. RESULTS: Six patients showed positive P. gingivalis bacteremia. The
      most frequent fimA was fimA type II, followed by Ib, III and IV. In blood
      strains, type II was followed by IV, Ib and III. CONCLUSION: Type II was the most
      frequent genotype in blood samples and in subgingival plaque samples. However, no
      correlation was found between the frequency of any fimA type with SRP induced
      bacteremia. P. gingivalis fimA type appears to be conserved within individual
      patients throughout the times of sample collection, fimA gene sequence results
      were not in agreement with results of fimA genotyping by PCR.

PMID- 20128355
TI  - [Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment
      for Plasmodium falciparum malaria and treatment effects on gametocytic
      development].
AB  - INTRODUCTION: The treatment of Plasmodium falciparum malaria requires a safe and
      effective therapeutic treatment regimen, which in turn has high impact on the
      transmission. In 2006, an artesunate (AS)-mefloquine (MQ) treatment program was
      implemented in Antioquia. In addition, primaquine (PQ) was added to eliminate
      malaria gametocytes in the bloodstream. OBJECTIVE: The efficacy and
      gametocytocidal activity was evaluated for two treatment regimens, AS-MQ-PQ and
      AS-MQ, in patients with uncomplicated P. falciparum malaria. MATERIALS AND
      METHODS: Between April 2007 and February 2008, 50 patients were recruited for the
      trial in Turbo, Antioquia. A randomized clinical trial was conducted. Treatment
      compliance was supervised, with a clinical and parasitological assessment on days
      1, 2, 3, 7, 14, 21, 28, 35, and 42 to evaluate response rate according to the WHO
      2003 protocol. RESULTS: Clinical response and parasite elimination efficacy of AS
      MQ (with or without PQ) was 100% (95% CI 86.3%-100%), and parasitemia and fever
      were absent on day 3 of treatment in all patients. Gametocyte elimination was
      superior when PQ was used--92% (95% CI: 74%-99%) of patients who received PQ had
      no gametocytes on day 3, compared to 78.3% (95% CI: 59%-93%) of patients who only
      received AS-MQ. Furthermore, circulating gametocytes were eliminated on average
      one week faster when the AS-MQ-PQ treatment scheme was used compared to the
      scheme without PQ. CONCLUSION: These studies recommend the use of AS-MQ to treat
      P. falciparum malaria given its good therapeutic efficacy. However, further
      assessment is suggested concerning the benefit of adding PQ to this treatment
      scheme.

PMID- 20128357
TI  - Research digest--the underground version.

PMID- 20128356
TI  - [Danger signs in the malaria patient].
AB  - Danger signs are clinical indicators of severity and are useful to predict
      complications or death. In the malaria patient, clinical or parasitological signs
      can be easily be recognized during the acute phase of the illness that indicate
      serious complications. Danger signs include neurological change, abnormal
      breathing pattern, persistent vomiting and diarrhea, jaundice, bleeding, dark
      urine, delayed capillary refill, intense pallor, hyperpyrexia, hyperparasitemia
      and schizontemia. Timely recognition of these signs can lead to a decrease in
      cases with complications and deaths.

PMID- 20128358
TI  - What do we really know about children's ability to perceive exertion? Time to
      consider the bigger picture.

PMID- 20128359
TI  - Physical activity assessed by accelerometry in rural African school-age children
      and adolescents.
AB  - Physical activity (PA) in children/adolescents of both genders from a rural
      community in Mozambique was estimated by accelerometry and by questionnaire and
      was compared with PA of Portuguese youth. Total PA, moderate (MPA), vigorous
      (VPA) and very vigorous (VVPA) were evaluated. Mozambican boys were more active
      than girls. Intensity of PA declined significantly with age. Survival activities,
      such as household tasks, were the predominant mode of PA. Compared with
      Portuguese children/adolescents, Mozambicans had significantly higher total PA;
      showed less decline of PA with age and engaged in fewer minutes at higher
      intensity PA. Environmental factors likely explain documented differences.

PMID- 20128360
TI  - Assessing physical activity preferences in Latino and white preadolescents.
AB  - The purpose of this study was to assess physical activity preferences (PAP) in
      preadolescent children. 191 Latino and White children (M = 11.9, SD = +/- 0.7)
      participated. Demographic, anthropometric, and PAP measures were employed. Both
      Latino and White children reported water play, basketball, and bicycling as their
      most preferred activities while indoor chores were least preferred. Compared with
      Latino, White children reported a higher preference for baseball/softball.
      Exploratory factor analysis of PAP measure indicated a three-factor solution:
      free play, sports, and exercise. Multiple linear regression models revealed that
      PAP varied as a function of ethnicity, gender, age, and body mass index.

PMID- 20128361
TI  - Preschool children physical activity measurement: importance of epoch length
      choice.
AB  - The purpose of this study was twofold: first to document the gender differences
      in Moderate to Vigorous Physical Activity (MVPA) according to two epoch systems
      (5 vs. 60 s) in preschoolers, and, second to document the differences in physical
      activity (PA) patterns according to two different epoch choices. The sample
      comprised 59 preschoolers (31 girls) aged 2-5 years old. PA was assessed by
      accelerometer during school hours. The time spent in MVPA was significantly
      higher (p < .001) when a 5-s epoch was considered compared to the 60-s epoch,
      regardless gender. Further, it was found a difference of ?17 min difference
      between the 2 epoch systems for MVPA. Different epoch times might affect the time
      spent in MVPA among preschool children.

PMID- 20128362
TI  - Examination of physical activity in adolescents over the school year.
AB  - This study monitored the physical activity behavior of adolescent students over a
      ten month school year. Physical activity was assessed at two month intervals
      using self-report and objective (Actical accelerometers) measures. Self-report
      results (n = 547) indicated a decline in physical activity throughout the school
      year for all grades and genders. The decline was attributed largely to a decrease
      in organized activity participation. Objective physical activity results (n = 40)
      revealed a significant decline in activity in the latter half of the school year
      (February to June). Declining physical activity was attributed to a decrease in
      vigorous activity which was consistent across grade and gender. Collectively, the
      results highlight the importance of promoting consistent opportunities for
      adolescents to be active throughout the school year.

PMID- 20128363
TI  - Relationships between fundamental movement skills and objectively measured
      physical activity in preschool children.
AB  - Gender differences in cross-sectional relationships between fundamental movement
      skill (FMS) subdomains (locomotor skills, object-control skills) and physical
      activity were examined in preschool children. Forty-six 3- to 5-year-olds (25
      boys) had their FMS video assessed (Test of Gross Motor Development II) and their
      physical activity objectively monitored (Actigraph 7164 accelerometers). Among
      boys, object-control skills were associated with physical activity and explained
      16.9% (p = .024) and 13.7% (p = .049) of the variance in percent of time in
      moderate-to-vigorous physical activity (MVPA) and total physical activity,
      respectively, after controlling for age, SES and z-BMI. Locomotor skills were
      inversely associated with physical activity among girls, and explained 19.2% (p =
      .023) of the variance in percent of time in MVPA after controlling for
      confounders. Gender and FMS subdomain may influence the relationship between FMS
      and physical activity in preschool children.

PMID- 20128364
TI  - The association between distance to school, physical activity and sedentary
      behaviors in adolescents: project STIL.
AB  - The purpose of this research was to investigate the relationship between distance
      to school and levels of physical activity and sedentary behavior in UK
      adolescents. Participants were 1385 adolescents (boys n = 531; mean age 14.7
      years). Boys living within two miles of school and girls living within 5 miles of
      school were more likely to report high levels (> or = 60 min per day) of weekday
      leisure time physical activity. Differences in weekday leisure time physical
      activity were accounted for by active travel time. There were no differences in
      sedentary behavior time by distance to school. Journeys, whether active or
      motorized, most often took place with friends. Further research should
      investigate wider physical and social environmental influences on active travel.

PMID- 20128365
TI  - Secular trends in youth physical activity and parents' socioeconomic status from
      1977 to 2005.
AB  - The aim of this study was to investigate the relationship between youth physical
      activity and family socioeconomic status (FSES) over 28 years. As a part of the
      Finnish Adolescent Health and Lifestyle Survey a random sample of 12-, 15- and 18
      year-old boys and girls participated in a nation-wide survey by answering
      questions every second year, from 1977 to 2005, on, among other things, leisure
      time physical activity and sport participation. Father's education represented
      FSES. The results showed that there were no significant or only small differences
      between the high and low FSES groups in unorganised physical activity during the
      study period. Participation in physical activities organized by the school was
      not associated with FSES. Participation in youth sport organized by sport clubs
      was strongly associated with FSES in both sexes. The young people in the high
      FSES groups participated more than those in the low FSES groups. It was concluded
      that considerable inequality exists in youth sport participation, that this
      inequality has been growing during the last decade, and that it is bigger among
      girls than among boys.

PMID- 20128366
TI  - Coaching behaviors, motivational climate, and psychosocial outcomes among female
      adolescent athletes.
AB  - Based on Harter's (12,13) competence motivation theory, this study examined the
      relationship of coaches' performance feedback and motivational climate with
      female athletes' perceived competence, enjoyment, and intrinsic motivation.
      Female adolescent soccer players (N = 141) completed measures of relevant
      constructs toward the latter part of their season. Canonical correlation analysis
      revealed that athletes' perceptions of greater positive and informational
      feedback given by coaches in response to successful performance attempts, greater
      emphasis placed on a mastery climate, and less emphasis placed on a performance
      climate, were significantly related to greater ability perceptions, enjoyment,
      and intrinsic motivation. Exploratory analyses also showed that the relationship
      between feedback and the psychosocial outcomes may vary as a function of the
      perceived motivational climate. Overall, these results suggest that coaching
      feedback and motivational climate are important contributors to explaining
      adolescent females' continued motivation to participate in sport.

PMID- 20128367
TI  - Predicting maximal lactate steady state in children and adults.
AB  - The value of blood lactate concentration (BLC) measured during incremental load
      tests in predicting maximal lactate-steady-state (MLSS) workload has rarely been
      investigated in children. In 17 children and 18 adults MLSS was 4.1 +/- 0.9 mmol
      l(-1). Workload at BLC of 3.0 mmol l(-1) determined during an incremental load
      test explained about 80% of the variance (p < .001) and best predicted MLSS
      workload independent of age. This was despite the increase in power per time
      related to maximum incremental load test power being higher (p < .001) in
      children than in adults. The BLC response to given exercise intensities is faster
      in children without affecting MLSS.

PMID- 20128368
TI  - Development and evaluation of a novel computer-based tool for assessing physical
      activity levels in schoolchildren.
AB  - A novel computer tool (peas@tees), designed to assess habitual physical activity
      levels in children aged 9 and 10 years, was evaluated. Study 1 investigated
      agreement between peas@tees and accelerometry in 157 children. Bland-Altman
      limits of agreement (LOA) revealed peas@tees underestimated physical activity
      levels compared with accelerometry (bias -21 min; 95% LOA -146-105). Study 2
      investigated stability of peas @ tees in a separate sample of 42 children.
      Intraclass correlation coefficient was 0.75 (95% CI 0.62-0.84). Computer tools
      are promising as a cheap, feasible, and useful method to monitor children's
      habitual levels of physical activity at the group level.

PMID- 20128369
TI  - The association between walking to school, daily step counts and meeting step
      targets in 5- to 17-year-old Australian children.
AB  - Objective measurement of daily steps was used to assess whether children (n =
      2,076) in Years 1, 5 and 10 who reported walking to or from school were more
      active and more likely to reach recommended step targets than those who were
      driven or took public transport to school. Walking to school was associated with
      higher school-day steps in older children (16,238 vs 15,275 for Year 5 male p <
      .05, 13,521 vs 12,502 for Year 5 female p < .01, 12,109 vs 11,373 for Year 10
      female p < .05). The proportion of children who met recommended step thresholds
      was higher in those who walked to school compared with those who took motorized
      transport, and this was significant for Year 5 females (71.7% vs 54.5%, p < .01).
      This study suggests that walking to school for older children has potential to
      contribute significantly to daily activity levels and increases the likelihood of
      attaining recommended step targets. These data should encourage public policy and
      those concerned with the built environment to provide and support opportunities
      for walking to school.

PMID- 20128370
TI  - [Comparison between drug eluting stent and coronary artery bypass grafting
      surgery for the treatment of unprotected left main coronary artery disease in
      elderly patients].
AB  - OBJECTIVE: To compare the 2 years outcome of elderly patients with ULMCA stenosis
      undergoing coronary artery bypass grafting (CABG) or drug eluting stent (DES).
      METHODS: From January 2004 to June 2006, 295 patients with ULMCA stenosis and age
      > or = 70 years undergoing coronary revascularization with either CABG (n = 206)
      or DES (n = 89) were enrolled in this analysis. All-cause death, non-fatal
      myocardial infarction and target lesion revascularization (TLR) were recorded
      during 2 years follow-up. RESULTS: The cumulative rate of 2-year mortality were
      10.2% (n = 21) in CABG-treated patients and 13.3% (n = 12) in DES-treated
      patients (P = 0.428). The survival rate during 2-year follow-up was 89.2% for
      CABG-treated patients and 86.4% for DES-treated patients (P = 0.668). The
      incidence of 2-year myocardial infarction was 7.8% (n = 16) in CABG-treated
      patients and 10.1% (n = 9) in DES-treated patients (P = 0.501). The incidence of
      target lesion revascularization (TLR) was 4.9% (n = 10) in CABG-treated patients
      and 13.5% (n = 12) in DES-treated patients (P = 0.015). In the multivariable
      analysis, age (HR: 1.04, 95% CI: 1.01-1.09, P = 0.024), left ventricular
      dysfunction (ejection fraction < 30%, HR: 4.97, 95% CI: 1.22-24.85, P = 0.018)
      and type 2 diabetes (HR: 2.22, 95% CI: 1.31-4.86, P = 0.001) were independent
      predictors of 2-year mortality. CONCLUSION: In this study, 2-year mortality was
      comparable in elderly patients with ULMCA stenosis underwent CABG or DES.
      However, the rate of TLR was significantly higher in patients treated with DES
      than that receiving CABG operation.

PMID- 20128371
TI  - [Long-term clinical outcomes of patients undergoing successful or failed
      percutaneous coronary intervention for chronic total occlusions of coronary
      arteries].
AB  - OBJECTIVE: To evaluate the long-term outcomes of successful or failed
      revascularization in patients with chronic total occlusions (CTO). METHODS: The
      clinical data of 1332 consecutive patients underwent percutaneous coronary
      intervention (PCI) for CTO between June 1993 and December 2006 in our hospital
      were analyzed. These patients were divided into two groups according to the
      procedural success (n = 1202) or failure (n = 130). RESULTS: Overall success rate
      of procedure was 90.2% (1202/1332). The patients in CTO success group experienced
      a superior 10-year survival rate (76.9% vs. 64.6%, log rank P = 0.012) and a
      significantly higher no major adverse cardiovascular event (MACE) survival rate
      (41.8% vs. 27.6%, log rank P < 0.001) compared to the patients in CTO failure
      group. During the long-term follow-up, the proportion of patients who accepted
      coronary artery bypass grafting (CABG) was significantly lower in CTO success
      group than that in the CTO failure group (4.3% vs. 14.6%, P < 0.001). CONCLUSION:
      Successful PCI procedure leads to increased long-term survival and MACE-free
      survival and the reduced need for CABG for patients with CTO lesions.

PMID- 20128372
TI  - [Association between smoking status at follow-up and clinical outcomes in
      patients undergoing successful percutaneous coronary intervention].
AB  - OBJECTIVE: To assess the association between smoking status at follow-up and
      clinical outcomes in patients undergoing successful percutaneous coronary
      intervention (PCI). METHODS: The smoking status at follow-up was investigated in
      592 patients undergoing successful PCI between Jan. 2003 and Nov. 2006. The
      patients were divided into three groups on the basis of their smoking status at
      follow-up: non-smokers (n = 272), quitters (n = 215) and current smokers (n =
      105). Major adverse cardiac events were recorded. RESULTS: The average follow-up
      time was 19.0 months. At follow-up, current smokers were significantly younger (P
      < 0.01), more likely to be male (P < 0.01) than non-smokers and had more
      favorable clinical and angiographic characteristics: lower prevalence of
      hypertension (P < 0.05) and diabetes (P < 0.05), fewer diseased vessels (P <
      0.05) and fewer implanted coronary stents (P < 0.01), larger target vessel
      diameter (P < 0.01). However, the incidence of non-fatal myocardial infarction
      (MI) in quitters (1.40%) was significantly higher than in nonsmokers (0.37%, P <
      0.05), the incidence of nonfatal MI in current smokers (4.76%) was significantly
      higher than quitters (1.40%, P < 0.05) and nonsmokers (0.37%, P < 0.01). After
      adjustments for age, gender, hypertension, diabetes, dyslipidaemia, target vessel
      diameter, the number of diseased vessels, the kind and number of implanted
      stents, and the follow-up time, multi-variables logistic regression analysis
      showed that current smoking was a independent predictive factor for non-fatal MI
      (beta = 1.28, wald chi2 = 6.91, P < 0.01). CONCLUSIONS: Smokers, especially
      current smokers, were at increased risk for non-fatal MI post successful PCI.
      Therefore, all patients underwent PCI should be encouraged to stop smoking.

PMID- 20128373
TI  - [The effects of different occluder selection on cardiac remodeling post
      transcatheter closure in patients with secundum atrial septal defect].
AB  - OBJECTIVE: To evaluate the effects on cardiac remodeling post transcatheter
      closure by Amplatzer septal occluder selected by oval circumference formula in
      patients with atrial septal defect (ASD). METHODS: A total of 146 patients with
      ASD (68 males,mean 33.5 years) treated by transcatheter closure with the
      Amplatzer occluder were enrolled in this study. The diameter of defects was
      corrected with the oval circumference formula (group A, 73 cases) or by
      echocardiography (group B, 73 cases). Cardiac remodeling was assessed by
      transthoracic echocardiography (TTE) before the procedure, 3 days, 3 months and 6
      months after ASD closure. RESULTS: The mean ASD diameter was similar between the
      two groups [(20.16 +/- 4.98) mm vs. (21.36 +/- 5.69) mm, P > 0.05] and the mean
      diameter of the selected occluder of group A was significantly smaller than that
      in group B [(21.95 +/- 6.78) mm vs. (25.85 +/- 6.75) mm, P < 0.05]. Procedural
      success rate was identical between the two groups (97.3%) and the defects were
      completely occluded and there was no residual shunt during the 6 months follow up
      period, there were also no complications during and after the procedure. The
      lateral diameter of right atrial (RALD), the diastolic diameter of right
      ventricle (RVDD), RALD/LALD, RVDD/LVDD and pulmonary diameter (PD) were
      significantly decreased while the lateral diameter of left atrial (LALD) and left
      ventricle (LVDD) were significantly increased post ASD closure in both groups. At
      6 months follow up, RALD decreased by (18.63 +/- 10.59)% in group A versus (10.14
      +/- 6.59)% in group B, LALD increased by (13.42 +/- 8.38)% in group A versus
      (9.28 +/- 4.95)% in group B and RALD/LALD ratio decreased by (26.35 +/- 11.24)%
      in group A versus (13.98 +/- 8.96)% in groups B (all P < 0.05). CONCLUSION: ASD
      occluder selection based on the oval circumferen ce formula is superior to that
      made by echocardiography in terms of more favorable cardiac remodeling post ASD
      closure.

PMID- 20128374
TI  - [Pathological analysis of aspirated materials from the culprit lesion in patients
      with acute myocardial infarction].
AB  - OBJECTIVE: To analyze the components of retrieved materials from the culprit
      lesion in ST-segment elevation myocardial infarction (STEMI) patients by manual
      aspiration during primary percutaneous coronary intervention (PCI). METHODS:
      Visible retrieved materials were collected, fixed in formalin and processed for
      paraffin embedding, sectioned and stained with hematoxylin and eosin (HE). The
      retrieved materials were microscopically divided into erythrocyte-rich thrombi,
      platelet/fibrin-rich thrombi, combined thrombi (similar proportions of
      erythrocytes and platelet/fibrin components), atherosclerotic plaque materials
      and edematous components. Based on pathological findings, thrombus materials were
      classified into fresh (< 1 d), lytic (1-5 d), fresh/lytic and organized thrombi
      (> 5 d) after formation. All patients were further classified into plaque
      positive and plaque negative groups. Clinical and angiographic data were also
      obtained for analyzing possible association between pathological findings and
      surrogates of myocardial reperfusion, including myocardial blush grade (MBG),
      enzymatic estimated infarction size (peak CK and CK-MB levels), left ventricular
      end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF)
      which were assessed 16 h after procedure. RESULTS: Visible samples were collected
      from 49 patients by manual catheter aspiration (thrombus components in 46
      patients, atherosclerotic plaque only in 3 patients). Frequency of erythrocyte
      rich thrombi, platelet/fibrin-rich thrombi and combined thrombi were 41.3%
      (19/46), 30.4% (14/46) and 28.2% (13/46), respectively. The incidence of fresh,
      lytic, fresh/lytic and organized thrombi were 47.8% (22/46), 32.6% (15/46), 10.9%
      (5/46) and 8.7% (4/46), respectively. Plaque materials were found in 57.1%
      (28/49) patients, including ruptured plaque accompanied by thrombus formation
      [8.2% (4/49)], fibrous plaque [6.1% (3/49)] and thickened intima [2.0% (1/49)].
      Baseline characteristics did not differ between plaque positive (n = 28) and
      plaque negative (n = 21) groups. Ratios of MBG 3 were higher in plaque positive
      group than in plaque negative group [82.1% (23/28) vs. 52.4% (11/21), P = 0.025].
      Peak CK and CK-MB levels were lower in the former than in the later [(1705 +/-
      1647) U/L vs. (2629 +/- 2013) U/L, P = 0.042; (146 +/- 136) microg/L vs. (258 +/-
      215) microg/L, P = 0.016; respectively]. Furthermore, LVEF were higher in plaque
      positive group than in plaque negative group (0.59 +/- 0.10 vs. 0.52 +/- 0.08, P
      = 0.012). CONCLUSION: Manual catheter aspiration during primary PCI in STEMI
      patients is an effective way for removing thrombus and plaque materials, and
      plaque debulking before stenting or pre-dilation and this procedure might
      probably improve myocardial reperfusion, limit infarction size and improve
      cardiac function.

PMID- 20128375
TI  - [Link between cardiac myosin binding protein-C gene mutation of Pro1208fs and
      Gly507 Arg and hypertrophic cardiomyopathy in Chinese patients].
AB  - OBJECTIVE: To detect gene mutations associated with hypertrophic cardiomyopathy
      (HCM) in Chinese patients and possible correlations between genotype and
      phenotype. METHODS: Twenty-one unrelated patients with hypertrophic
      cardiomyopathy were studied. The clinical data including symptoms, physical
      examination, echocardiography and electrocardiography were collected. The full
      ecoding exons of cardiac myosin-binding protein C gene (cMYBPC3) were amplified
      with PCR and the products were sequenced. RESULTS: Two mutations were identified
      in probands from two families. One mutation was frame shift mutation Pro1208fs in
      the exon 32 of the cMYBPC3 gene. Pro1208fs mutation was identified in a 59 years
      old female patient with familial hypertrophic cardiomyopathy. Symptom onset was
      late and a favorable clinical course was evidenced in this patient. Another
      mutation was missence mutation Gly507Arg in the exon 17 of the MYBPC3 gene
      identified in a 24 years old male patient. Diffuse thickness of left ventricular
      wall, impaired diastolic function and enlarged left atria were evidenced in
      echocardiography. No mutation was identified in the 80 control healthy
      individuals. CONCLUSION: cMYBPC3 might be the disease-causing genes in Chinese
      patients with hypertrophic cardiomyopathy.

PMID- 20128376
TI  - [Efficacy and safety of the single pill combination of valsartan 80 mg plus
      amlodipine 5 mg in mild to moderate essential hypertensive patients without
      adequate blood pressure control by monotherapy].
AB  - OBJECTIVE: To evaluate the efficacy and safety of a once daily
      valsartan/amlodipine 80/5 mg combination tablet in Chinese mild to moderate
      hypertensive patients without adequate blood pressure control by monotherapy.
      METHODS: Two multicenter, randomized, double-blind, double dummy, active
      controlled, parallel group trials were conducted. After a washout period (no
      medication) of 1-4 weeks, patients with Mean Sitting Diastolic Blood Pressure
      (MSDBP) > or = 95 mm Hg (1 mm Hg = 0.133 kPa) and < 110 mm Hg received a
      monotherapy of either Amlodipine 5 mg (in study 1) or valsartan 80 mg (in study
      2) for 4 weeks. Patients with MSDBP > or = 90 mm Hg and < 110 mm Hg at the end of
      the monotherapy period were randomized to receive valsartan/amlodipine 80/5 mg
      treatment, or continue with the monotherapy. RESULTS: In study 1, compared with
      amlodipine 5 mg, valsartan/amlodipine 80/5 mg once daily further reduced mean
      sitting systolic blood pressure (MSSBP)/MSDBP 4.4/3 mm Hg (P < 0.0001). In study
      2, compared with valsartan 80 mg, valsartan/amlodipine 80/5 mg once daily further
      reduced MSSBP/MSDBP 6.4/4.2 mm Hg (P < 0.0001). The blood pressure (BP) control
      rates (BP < 140/90 mm Hg) of combination treatment group were 71.0% and 71.2%
      respectively, and significantly higher than the monotherapy groups in both
      trials. Incidence of adverse events was comparable in monotherapy and combination
      therapy groups. CONCLUSION: Our results showed that valsartan/amlodipine 80/5 mg
      was superior to amlodipine 5 mg or valsartan 80 mg alone in lowering blood
      pressure and BP control in patients with mild to moderate hypertension not
      adequately controlled with amlodipine 5 mg or valsartan 80 mg monotherapy. No new
      or unexpected safety issues were identified with valsartan/amlodipine combination
      therapy compared with monotherapy.

PMID- 20128377
TI  - [Plasma endothelin level in hypertensive patients receiving standard anti
      hypertensive therapy with or without statins].
AB  - OBJECTIVE: To observe the association between plasma endothelin (ET)
      concentration and blood pressure level in essential hypertensive (EH) patients
      with or without complications and possible impact of statins on ET concentration.
      METHODS: From Sep 2007 to Mar 2009, 149 patients with EH were analyzed [44 EH, 40
      EH complicated by left ventricular hypertrophy (EH-LVH), 36 EH complicated by
      atrial fibrillation (EH-AF), and 29 EH complicated by lacunar infarction (EH
      LI)], 30 healthy persons were selected as controls. EH patients were randomly
      divided into routine treatment group (calcium antagonists, ACEI, diuretics, beta
      receptor blocker for 8 weeks) and simvastatin intervention group (routine
      treatment + simvastatin 40 mg/d for 8 weeks), plasma ET concentrations before and
      after drug intervention were measured. RESULTS: (1) ET concentration was higher
      in EH group than that in control group [(71.42 +/- 6.62) pg/ml vs. (45.52 +/-
      8.28) pg/ml, P < 0.01]. ET concentration was higher in EH-LVH group, EH-AF group
      and EH-LI group than that in EH group [(97.67 +/- 10.53) pg/ml, (102.15 +/-
      12.96) pg/ml, (103.49 +/- 9.91) pg/ml vs. (71.42 +/- 6.62) pg/ml, P <0.01]. The
      degrees of elevated blood pressure was positively correlated with ET
      concentrations(all P < 0.001). (2) The left atrial diameters of EH-AF group were
      positively correlated with ET concentration (r = 0.684, P < 0.001). The left
      ventricular mass index of EH-LVH group were positively correlated with ET
      concentration (r = 0.545, P < 0.001). (3) The percentages of class 3 hypertension
      in EH-LVH group, EH-AF group and EH-LI group were higher than that in EH group
      (57.5%, 50.0%, 62.1% vs. 25.0%, all P < 0.05). (4) Blood pressure in class 3
      hypertension patient treated with simvastatin decreased more significantly than
      that in routine treatment group (P < 0.05). (5) ET concentration of class 2
      hypertension patient treated with simvastatin decreased significantly than that
      in routine treatment group (P < 0.05). ET concentrations of class 3 hypertension
      patient treated with simvastatin and routine treatment patient decreased
      significantly after treatment (P < 0.05), and the former was lower (P < 0.05).
      CONCLUSION: The level of ET were positively correlated with the severity of EH.
      Simvastatin could decrease the ET levels of patients with EH and blood pressure
      levels of patients with class 3 hypertension. It suggested that therapeutic
      alliance of antihypertensive drugs and statins could be benefit to patients with
      EH.

PMID- 20128378
TI  - [Plasma N-terminal pro-B-type natriuretic peptide reference value in subjects
      without heart diseases].
AB  - OBJECTIVE: To determine the reference value of plasma N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) in subjects without heart diseases. METHODS: The
      plasma concentration of NT-proBNP was measured with ELISA method in 300 adults
      excluded heart disease through various examinations including
      electrocardiography, echocardiography, X-ray and coronary artery angiography. The
      plasma NT-proBNP concentration was compared between age-groups 30-39, 40-49, 50
      59, 60-69 and > or = 70 years old, between male and female in the same age-group
      and between subjects with and without hypertension, diabetes and obesity. A
      multiple linear regression analysis was used to detect factors influencing NT
      proBNP among age, sex, body mass index, blood pressure, heart rate, serum
      creatinine, hypertension, diabetes mellitus, use of angiotensin-converting-enzyme
      inhibitors, Ca(2+)-antagonist, and beta-blocker. RESULTS: The plasma NT-proBNP
      concentration increased in proportion to aging in male subjects more than 60
      years old (P < 0.05), remained unchanged in males less than 60 years old and
      females (P > 0.05). Plasma NT-proBNP concentration was significantly higher in
      female (170-660 pmol/L) than in male (160-470 pmol/L) in subjects less than 60
      years old (P < 0.05) and significantly lower in female (180-560 pmol/L) than in
      male (180-760 pmol/L) in subjects more than 60 years old (P < 0.05). Multiple
      linear regression analysis demonstrated that age was the only independent
      predictor for plasma NT-proBNP in these subjects (P < 0.01). CONCLUSION: The
      plasma concentration of NT-proBNP in subjects without heart diseases was
      different between male and female, and was increasing with age in male subjects
      more than 60 years old.

PMID- 20128379
TI  - [Reduced left ventricular systolic atrioventricular plane displacement in heart
      failure patients with preserved ejection fraction].
AB  - OBJECTIVE: To determine whether patients with suspected heart failure but
      preserved left ventricular ejection fraction (LVEF) have systolic dysfunction in
      left ventricular long axis detected by left ventricular systolic atrioventricular
      plane displacement (AVPD). METHODS: The data of 96 patients with heart failure
      who admitted to our hospital between August 2007 and October 2008 were collected.
      Heart failure with preserved LVEF was diagnosed in 48 patients and heart failure
      with reduced LVEF was diagnosed in another 48 patients. Fifty age-matched healthy
      subjects served as the control group. The NYHA classification, etiology of heart
      failure, AVPD and plasma NT-proBNP concentration were compared among the 3
      groups. RESULTS: There was no difference in terms of NYHA classification between
      patients with preserved LVEF and reduced LVEF. Hypertension and coronary heart
      disease were often diagnosed in heart failure patients with preserved LVEF. The
      degree of AVPD decrease was more significant in heart failure patients with
      reduced LVEF than those with preserved LVEF. In all subjects, the AVPD was
      negatively correlated with the NT-proBNP concentration (r = -0.35, P < 0.05).
      CONCLUSION: Left ventricular systolic atrioventricular plane displacement was
      decreased in heart failure patients with preserved LVEF, therefore, besides
      "diastolic heart failure", systolic dysfunction was also impaired in these
      patients.

PMID- 20128380
TI  - [Relationship between atrial fibroblast proliferation/fibrosis and atrial
      fibrillation in patients with rheumatic heart disease].
AB  - OBJECTIVE: To investigate the association between gene expressions of basic
      fibroblast growth factor (bFGF), smooth muscle alpha-actin (alpha-SMA) and
      proliferating cell nuclear antigen (PCNA) and atrial fibrosis in patients with
      atrial fibrillation (AF). METHODS: The right atrial tissue samples were taken
      from 75 patients with rheumatic heart disease underwent heart valve replacement
      surgery (34 patients with sinus rhythm, 11 patients with paroxysmal AF and 30
      patients with persistent AF) and stained with picrosirius red for quantitative
      analysis of collagen accumulation. The mRNA and protein levels of bFGF, alpha-SMA
      and PCNA were detected by semi-quantitative reverse transcription polymerase
      chain reaction (RT-PCR) and immunohistochemical technique, respectively. RESULTS:
      The percent volume fraction of collagen (CVF) was the highest in persistent AF
      group and the lowest in the sinus rhythm group (all P < 0.01). CVF significantly
      correlated with AF duration (r = 0.390, P = 0.010) and left atria (LA) dimension
      (r = 0.320, P = 0.005). The mRNA and protein levels of bFGF, alpha-SMA and PCNA
      were significantly higher in the persistent AF group than those in the paroxysmal
      AF group (all P < 0.05) and significantly higher in both AF groups than those in
      the sinus rhythm group (P < 0.05-0.01). The mRNA and protein levels of bFGF were
      positively correlated with CVF (r = 0.330, P = 0.004 and r = 0.292, P = 0.013,
      respectively), AF duration (r = 0.330, P = 0.005 and r = 0.299, P = 0.010,
      respectively) and left atrial dimension (r = 0.342, P = 0.003 and r = 0.285, P =
      0.015, respectively). CONCLUSION: The increased gene expressions of bFGF, alpha
      SMA and PCNA in atrium during AF may contribute to atrial fibrosis by promoting
      fibroblast proliferation in AF patients.

PMID- 20128381
TI  - [Value of combined wells score and D-dimer test on diagnosing patients with deep
      venous thrombosis].
AB  - OBJECTIVE: To evaluate the value of Wells score or/and D-dimer test on diagnosing
      or excluding deep venous thrombosis (DVT). METHODS: Patients with suspected DVT
      were retrospectively analyzed. All patients underwent clinical assessment, D
      dimer assay and bilateral lower extremity compression sonography within 48 hours
      of admission. The sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) for diagnosing DVT by Wells score, D-dimer test,
      and combined Wells score and D-dimer were compared. RESULTS: A total of 274
      patients were analyzed. If low probability was defined as negative and moderate
      and high probabilities were defined as positive, the sensitivity, specificity,
      PPV and NPV of the Wells score were 78.4%, 66.1%, 52.3% and 86.6%, respectively.
      At a cut-off of 500 microg/L, the sensitivity, specificity, PPV and NPV of D
      dimer test were 73.9%, 66.1%, 50.8% and 84.2%, respectively. If low probability
      and D-dimer < 500 microg/L were defined as negative, moderate and high
      probabilities and D-dimer > or = 500 microg/L were defined as positive, the
      sensitivity, specificity, PPV and NPV of the combined Wells score and D-dimer
      test were 88.3%, 76.8%, 67.1% and 92.5%, respectively. CONCLUSION: For clinical
      suspected DVT patients, DVT diagnosis could be reliably obtained by combined
      Wells score and D-dimer test.

PMID- 20128382
TI  - [Surgical treatment of aortico-left ventricular tunnel].
AB  - OBJECTIVE: To review 9 aortico-left ventricular tunnel (ALVT) patients in our
      hospital, describe the clinical features, diagnosis, treatments and follow-up.
      METHODS: We identified 9 patients from July 2002 to August 2008. Clinical and
      surgical details were reviewed. 7 patients were in NYHA class I and 2 in class
      III, 8 of 9 patients were diagnosed by echocardiography before operation.
      RESULTS: All patients underwent surgery under standard cardiopulmonary bypass. 2
      with direct suture, 5 by patch closure of the aortic end and 1 by patch closure
      of both aortic end and left ventricular end of the AVLT. 1 underwent aortic valve
      replacement after incision of the ALVT. One patient died 2 month after operation
      because of endocarditis and acute heart failure. At follow-up (3 month to 6
      years), 3 patients were in NYHA class I, 3 in Class II, 1 in class III and missed
      1. No aortic regurgitation or trace in 2, little in 1, little to moderate in 2.
      The aortic mechanical valve is normal in 1 and paravalvular leakage in 1 patient.
      CONCLUSION: Aortico-left ventricular tunnel is a rare cardiac malformation with a
      good post-operative outcome. Surgery is an effective treatment. Long-term follow
      up for post-operation is essential.

PMID- 20128383
TI  - [Association between wnt signal pathway and post-infarction cardiac
      remodeling/rupture in aged mice].
AB  - OBJECTIVE: To observe the association between wnt signal pathway and post
      infarction left ventricular remodeling/rupture in mice with various ages.
      METHODS: Three months-old (young group, n = 116) and 18 months-old (aged group, n
      = 116) male C57/BL mice were studied. Seventy mice underwent ligation of left
      coronary artery, 10 sham-operation and echocardiography and hemodynamics were
      performed 7 d post-infarction, 36 infarcted mice were used for detecting
      expression of dvl-1, beta-catenin and connexin 43 in left ventricular (LV)
      myocardium and infarction region at 3 d, 7 d, 14 d post infarction (n = 12 each).
      RESULTS: Incidence of cardiac rupture was significantly higher in aged mice than
      in young mice (36.7% vs. 16.7%, P < 0.05) and degree of LV dilation and
      contractile dysfunction was significantly severer in aged mice than those in
      young mice post infarction. Expression of dvl-1, beta-catenin in left ventricle
      was upregulated in MI group compared with sham group (P < 0.05), expression of
      dvl-1 and beta-catenin in infarction region in MI 3d group in aged mice was
      significantly downregulated than in young mice (P < 0.05). Expression of connexin
      43 is 2.15 fold higher in young sham mice than in aged sham mice (P < 0.05) and
      decreased significantly post infarction (P < 0.05). Expression of connexin 43 in
      infarction region in mice 3 d and 14 d post infarction was significantly lower in
      aged mice than in respective young mice (all P < 0.05). CONCLUSION: Reductant
      activation of wnt signal pathway post infarction in aged mice might be
      responsible for increased incidence of cardiac rupture and aggravated remodeling.

PMID- 20128384
TI  - [The effect of protease-activated receptor2 on rat apoptotic cardiomyocytes
      underwent ischemia reperfusion injury].
AB  - OBJECTIVE: To investigate the effect of protease-activated receptor 2 (PAR-2) on
      rat apoptotic cardiomyocytes underwent ischemia reperfusion (I/R) injury.
      METHODS: Healthy male Sprague-Dawley rats were randomly divided into five groups
      (n = 8 each): sham-operation group, I/R (ligating the left coronary artery for 30
      minutes and followed by 120 minutes reperfusion) group and three SLIGRL-NH2
      groups treated with intravenous PAR-2 agonist SLIGRL-NH2 at different doses (0.5,
      1, 3 mg/kg) 5 minutes before reperfusion. Apoptic cardiomyocytes was detected by
      TUNEL staining and by DNA ladder on agarose gel electrophoresis. Bax and Bcl-2
      expression in myocardium was analyzed by immunohistochemical technique. The mRNA
      expression of PAR-2 was determined by Real-time quantitative polymerase chain
      reaction (RT-PCR). RESULTS: (1) The apoptosis index and the expression of Bcl-2
      and Bax were significantly increased in IR group and SLIGRL-NH2 groups than those
      in sham group (P < 0.05-0.01). (2) Compared with I/R group, the apoptosis index
      and the expression of Bax were significantly reduced while the expression of Bcl
      2 and PAR-2 mRNA were significantly upregulated by SLIGRL-NH2 in a dose-dependent
      manner. (3) DNA Agarose gel electrophoresis demonstrated that DNA ladder existed
      in I/R and 0.5 mg/kg SLIGRL-NH2 group, but not in 1, 3 mg/kg SLIGRL-NH2 groups.
      CONCLUSIONS: PAR-2 agonist SLIGRL-NH2 could reduce myocardial apoptosis by
      upregulating the Bcl-2 and PAR-2 mRNA level and downregulating Bax expression in
      a dose-dependent manner in this rat I/R model.

PMID- 20128385
TI  - [Effect of small interfering RNA on matrix metalloproteinase-9 expression in
      vascular endothelial cells stimulated by serum from children with Kawasaki
      disease].
AB  - OBJECTIVE: To investigate the matrix metalloproteinase-9 (MMP-9) expression in
      vascular endothelial cells stimulated by the serum obtained from children with
      Kawasaki disease (KD) during the acute phase in the absence and presence of MMP-9
      small interfering RNA (siRNA). METHODS: MMP-9 siRNA plasmids were constructed and
      transduced into vascular endothelial cells (ECV-304) by liposomal transfection.
      ECV-304 were cultured in 6 different conditional media: KD serum + siRNA negative
      control, normal serum, KD serum + MMP-9 siRNA1 (pSilencer3.1-MMP1), KD serum +
      MMP-9 siRNA2 (pSilencer3.1-MMP2), KD serum + gamma-globulin, and KD serum. RT-PCR
      and Western blot were used to detect MMP-9 expression at mRNA and protein levels
      in ECV-304. RESULTS: The mRNA and protein expression of MMP-9 in ECV-304 cultured
      with 10% serum from KD patients (2.49 +/- 0.03, 1.20 +/- 0.04) and KD serum +
      siRNA negative control plasmid (2.45 +/- 0.03, 1.15 +/- 0.03) were significantly
      higher than those cultured with 10% serum from normal control children (1.21 +/-
      0.03, 0.52 +/- 0.03, respectively; all P < 0.01) and the increased MMP-9
      expression could be significantly inhibited by MMP-9 siRNA1, MMP-9 siRNA2 and
      gamma-globulin (100 mg/ml, all P < 0.01). CONCLUSIONS: The increase of MMP-9
      expression in vascular endothelial cells induced by the serum from KD patients
      might take part in the formation of coronary artery lesions. Two customized MMP-9
      siRNA plasmids (pSilencer3.1-MMP1 and pSilencer3.1-MMP2) can significantly
      inhibit both MMP-9 mRNA and protein expression.

PMID- 20128386
TI  - [In vitro growth and function of neonatal cardiomyocytes in various transcatheter
      closure device patches].
AB  - OBJECTIVE: To observe the effects of collagen-coating, epidermal growth factor
      (EGF), Bromodeoxyuridine (BrdU) on growth and function of neonatal ventricular
      cardiomyocytes in transcatheter closure device patches in vitro. METHODS:
      Neonatal ventricular cardiomyocytes were cultured with transcatheter closure
      device patches (1 cm x 2 cm) coated with or without collagen and treated with 10%
      FBS (control), EGF (20 ng/ml), BrdU (0.1 mmol/L), respectively. In vitro
      ventricular cardiomyocytes growth and function as well as IGF-I content were
      determined. RESULTS: (1) The beginning time of ventricular cardiomyocytes beating
      on patches was similar in collagen-coated and uncoated patches treated with PBS,
      EGF or BrdU, respectively (P > 0.05). The cell beating time was significantly
      earlier in Brdu group than in PBS and EGF groups (all P < 0.05). (2) Time of
      cultured cell covering on patches was significantly earlier in coated patches
      than those uncoated patches in PBS, EGF and BrdU treated groups (all P < 0.05).
      The ventricular cardiomyocytes covering time on patches was significantly earlier
      in EGF group than that in PBS and BrdU groups (all P < 0.05). (3) Ventricular
      cardiomyocytes types survived on patches included endothelial cells, fibroblasts
      and myocytes. The highest content of endothelial cells was evidenced in EGF group
      and the highest content of fibroblasts was found in Brdu group. Myocytes content
      was similar between PBS and BrdU groups (P > 0.05) and significantly higher than
      that in EGF group (all P < 0.05). (4) IGF-I peaked at the seventh culture day in
      all groups (all P < 0.01). CONCLUSIONS: Ventricular cardiomyocytes covering on
      patches could be enhanced by collagen coating. EGF could promote endothelial
      cells growth while Brdu could stimulate fibroblasts growth on patches.

PMID- 20128387
TI  - [Defibrillation efficacy of a newly developed automated external defibrillator in
      a swine ventricular tachycardia/fibrillation model].
AB  - OBJECTIVE: The aim of this study was to evaluate the recognition and
      defibrillation efficiency of a newly developed automated external defibrillator
      (AED). METHOD: Ventricular tachycardia (VT)/ventricular fibrillation (VF) was
      induced by alternating current (50 Hz) through an electrode placed on apex of
      right ventricle in 23 anesthetized swine and recorded, recognized and
      defibrillated by a newly developed AED. RESULTS: A total of 96 VF was induced and
      145 defibrillations were recorded. We analyzed available 167 electrocardiosignal
      with a total length of 103,740 seconds. The accuracy, sensitivity and the
      specificity of the AED on VT/VF recognition are 99.5%, 98.2% and 99.6%,
      respectively. The success rate of defibrillation was 33.4% which increased in
      proportion to defibrillation energy. The defibrillation threshold of energy is
      29.10-116.91 (78.75 +/- 35.64) J, the defibrillation threshold of electric
      quantity is (0.11 +/- 0.04) C and the defibrillation threshold of voltage is
      (1216.67 +/- 260.87) V. CONCLUSIONS: This newly developed AED has high
      sensitivity and the specificity on recognizing VT/VF. The lower success rate of
      defibrillation of this AED is associated with the low defibrillation energy
      during defibrillation which needs to be improved on further development.

PMID- 20128388
TI  - [Epidemiological study on plasma lipid among patients with cardiovascular disease
      in 9 cities of the Pearl River Delta region].
AB  - OBJECTIVE: To compare the plasma lipid levels among hospitalized patients with
      cardiovascular diseases in 1995 and 2005 in the Pearl River delta region. METHOD:
      Representative samples of 8040 patients were obtained from 16 3A hospitals in the
      Pearl River Delta region and 2239 patients hospitalized in 1995 and 5801 patients
      hospitalized in 2005 were analyzed. RESULTS: (1) Numbers of hospitalized patients
      with hypertension, hypertension and coronary artery disease (CAD) or CAD risk
      equivalent and patients with hypertension and CAD and CAD risk equivalent were
      significantly increased in 2005 compared with 1995 (all P = 0.000). (2)
      Triglycerides (P = 0.033) and high-density lipoprotein cholesterol (HDL-C) (P =
      0.000) levels from hospitalized patients were significantly higher while low
      density lipoprotein cholesterol (LDL-C) level (P = 0.000) was significantly lower
      in 2005 than those in 1995. (3) HDL-C levels of female patients were
      significantly higher than those of male patients in 1995 (P = 0.045) and 2005 (P
      = 0.000). (4) The highest cholesterol levels were found in patients with
      hypertension in 1995 and 2005. LDL-C level was the highest and HDL-C level was
      the lowest in patients with hypertension and CAD or CAD risk equivalent in 1995.
      The highest LDL-C level was found in hypertension patients in 2005. CONCLUSIONS:
      LDL-C level in hospitalized patients with CAD related diseases were significantly
      decreased in 2005 compared that in 1995 partly due to the widespread use of lipid
      lowering drugs. Proportion of hospitalized patients with hypertension,
      hypertension with CAD or CAD risk equivalent, hypertension with CAD and CAD risk
      equivalent were significantly higher in 2005 compared with that in 1995.

PMID- 20128389
TI  - [Cholesterol absorption, synthesis markers and coronary heart disease].

PMID- 20128390
TI  - [Progress of growth differentiation factor-15 in cardiovascular diseases].

PMID- 20128391
TI  - [Mind the web!].

PMID- 20128392
TI  - [Cognitive impairment in patients with alcoholism after long-term abstinence].
AB  - Patients with alcoholism display impaired cognitive information processing. In
      this study, we use clinically useful and effective neurocognitive tests to
      investigate these impairments. Twenty patients with the DSM-IV diagnosis of
      alcohol dependency and 20 age-, gender-, education-, and IQ-matched healthy
      control subjects participated in the study. The patients were abstinent for more
      than 6 months. For the assessment of neurocognitive impairment, listening span
      and backward digit span (working memory), Trail Making A, Trail Making B,
      semantic fluency (executive functions), digit span, world list task (short-term
      verbal memory) and the Digit Symbol Substitution Task (attention) were used. As a
      complex background test battery, we also used the Rivermead Behavioral Memory
      Test. Patients with alcoholism, even after a long period of abstinence, showed
      significant impairment in some cognitive domains, including executive functions
      and speed of processing. Inverse correlation was observed between the duration of
      the abstinent period and the deficit in the Trail Making task and the semantic
      fluency task. On the other hand, episodic memory and delayed memory functions
      were intact. These results show that in some cognitive domains (executive
      functions and semantic fluency), the performance is related to the duration of
      the abstinent period, which may suggest the recovery of these functions. Some
      other domains do not show such an improvement, which could be due to a primary
      deficit or to a slower recovery process.

PMID- 20128393
TI  - [Why do Hungarian men die early?].
AB  - The mortality rate for 40- 69-year-old men was 12.2/thousand males of
      corresponding age in 1960 and 16.2 in 2005: it increased by 33%, while among 40-
      69-year-old women it decreased from 9.6 0/thousand females of corresponding age
      to 7.8. The aim of the present follow up study was to analyze which psychosocial
      risk factors might explain the high premature mortality rates among Hungarian
      men. Participants in the Hungarostudy 2002 study, a nationally representative
      sample, 1130 men and 1529 women were contacted again in the follow up study in
      2006, who in 2002 were between the age of 40-69 years. By 2006, 99 men (8.8%) and
      53 women (3.5%) died in this age group. Socio-economic, psychosocial and work
      related measures, self-rated health, chronic disorders, depressive symptoms
      (BDI), WHO well-being, negative affect, self-efficacy, meaning in life and health
      behavioral factors were included in the analysis. After adjustment according to
      smoking, alcohol abuse, BMI, education and age, a number of variables were
      significant predictors of mortality only in men: low education, low subjective
      social status, low personal and family income, insecurity of work, no control in
      work, severe depression, no meaning in life, low social support from spouse, low
      social support from child. Socio-economic and work related risk factors predicted
      only male premature death. Among women dissatisfaction with personal relations
      was the most important risk factor. Among men depression seems to mediate between
      these chronic stress factors and premature death.

PMID- 20128394
TI  - [Child-adolescent psychiatry to adult psychiatry: can we find those disorders in
      adulthood which are typically diagnosed in childhood?].
AB  - The aim of the current study is to provide a short overview on autism, attention
      deficit hyperactivity disorder (ADHD) and Tourette syndrome. According to
      international data, the prevalence of autism is 2-60/10000 and the symptoms
      persist during the entire life; the prevalence of ADHD among children and
      adolescents is 2,4-12,0% and the symptoms cause problem in 30-50% in adults as
      well; while the prevalence of tic disorder is 1-6,6% among children and
      adolescents and the symptoms persist in 10% in adulthood. According to Hungarian
      data, these disorders are relatively rare in adult psychiatric practice.
      Presenting case reports of adults with autism, ADHD and Tourette syndrome, we
      would like to demonstrate the symptoms, treatment possibilities of these
      disorders and how they can influence the patients' quality of life.

PMID- 20128395
TI  - The role of carbon dioxide (and intracellular pH) in the pathomechanism of
      several mental disorders. Are the diseases of civilization caused by learnt
      behaviour, not the stress itself?
AB  - The role of carbon dioxide (CO2) is underestimated in the pathomechanism of
      neuropsychiatric disorders, though it is an important link between psyche and
      corpus. The actual spiritual status also influences respiration (we start
      breathing rarely, frequently, irregularly, etc.) causing pH alteration in the
      organism; on the other hand the actual cytosolic pH of neurons is one of the main
      modifiers of Ca2+-conductance, hence breathing directly, quickly, and effectively
      influences the second messenger system through Ca2+-currents. (Decreasing pCO2
      turns pH into alkalic direction, augments psychic arousal, while increasing pCO2
      turns pH acidic, diminishes arousal.) One of the most important homeostatic
      function is to maintain or restore the permanence of H+-concentration, hence the
      alteration of CO2 level starts cascades of contraregulation. However it can be
      proved that there is no perfect compensation, therefore compensational mechanisms
      may generate psychosomatic disorders causing secondary alterations in the "milieu
      interieur". Authors discuss the special physico-chemical features of CO2, the
      laws of interweaving alterations of pCO2 and catecholamine levels (their feedback
      mechanism), the role of acute and chronic hypocapnia in several hyperarousal
      disorders (delirium, panic disorder, hyperventilation syndrome, generalized
      anxiety disorder, bipolar disorder), the role of "locus minoris resistentiae" in
      the pathomechanism of psychosomatic disorders. It is supposed that the diseases
      of civilization are caused not by the stress itself but the lack of human
      instinctive reaction to it, and this would cause long-lasting CO2 alteration.
      Increased brain-pCO2, acidic cytosol pH and/or increased basal cytosolic Ca2+
      level diminish inward Ca2+-current into cytosol, decrease arousal--they may cause
      dysthymia or depression. This state usually co-exists with ATP-deficiency and
      decreased cytosolic Mg2+ content. This energetical- and ion-constellation is also
      typical of ageing-associated and chronic organic disorders. It is the most
      important link between depression and organic disorders (e.g. coronary heart
      disease). The above-mentioned model is supported by the fact that H+ and/or Ca2+
      metabolism is affected by several drugs (catecholemines, serotonin, lithium,
      triaecetyluridine, thyroxine) and sleep deprivation, they act for the logically
      right direction.

PMID- 20128397
TI  - [In waves' parlance: serotonin and sleep oscillations].
AB  - The close and complex relationship between serotonin and sleep-waking states has
      special theoretical and practical importance. There are available scientific data
      regarding this issue, but the apparently contradictory and insufficiently
      clarified nature of the problem halts up the systematization and exploitation of
      this knowledge. While reviewing the role of serotonin in sleep regulation a
      special attention to the differentiation between the immediate arousing and the
      slowly developing circadian phase resetting and sleep homeostatic functions of
      serotonin is paid. As regarding the differentiation of receptor subtypes the
      article focuses on circadian rhythm and REM regulatory/modulatory functions in
      relation with 5-HT1A/7 and 5-HT3 receptors, as well as on sleep homeostasis,
      sleep intensity, ultradian sleep organization, and sleep continuity in relation
      with 5-HT2A receptors. Moreover, there is suggestive data for the reciprocal
      interactions between serotonin, neural plasticity and sleep spindling, which
      might provide new insights to the neuropsychopharmacological characterization of
      the mechanisms of action and effects of drugs acting through the serotonergic
      system.

PMID- 20128398
TI  - Get ready for the age wave.

PMID- 20128399
TI  - It's not your parents' Medicare.

PMID- 20128400
TI  - Our genes, not the whole story.

PMID- 20128401
TI  - The dawning of a ripe old age.

PMID- 20128402
TI  - How exercise can boost longevity.

PMID- 20128403
TI  - Sailing past 90 with lots left to do.

PMID- 20128404
TI  - We will be what we eat.

PMID- 20128405
TI  - The first boomer's heart battle.

PMID- 20128406
TI  - A 10-week plan for (finally) getting fit.

PMID- 20128408
TI  - Beware: your job may be killing you.

PMID- 20128407
TI  - Afraid you'll get Alzheimer's? How to lower the odds.

PMID- 20128409
TI  - Dealing with the hormone dilemma.

PMID- 20128410
TI  - Nursing homes' new face.

PMID- 20128411
TI  - One family's saga of Alzheimer's care.

PMID- 20128412
TI  - Covering the cost of long-term care.

PMID- 20128414
TI  - America's best nursing homes.

PMID- 20128413
TI  - Taking the measure of the latest rankings.

PMID- 20128415
TI  - Guidelines on the clinical usefulness of determination of specific immunoglobulin
      E to foods.
AB  - The diagnostic gold standard for food allergy is challenge with the culprit food,
      particularly in double-blind placebo-controlled challenge. This approach involves
      risks and consumes both time and resources. A more efficient system would be
      desirable. The detection of serum specific immunoglobulin E (sIgE) against the
      culprit food enables us to establish sensitization, although this is not always
      accompanied by clinical reactivity. Age, symptoms (immediate/late reaction,
      local/systemic reaction), concomitant condition (eg, atopic dermatitis,
      pollinosis) and selection sample criteria (eg, presence of symptoms related to
      ingestion, positive skin prick test result) can influence the detection and
      concentration of IgE against foods. We analyze the clinical usefulness of sIgE
      determination in light of studies in which oral food challenge is used as the
      diagnostic method. We review clinical usefulness at diagnosis and in the decision
      to reintroduce the food, as well as the prognostic value of the determination of
      IgE to foods.

PMID- 20128416
TI  - Polymorphisms in IL4 and iLARA confer susceptibility to asthma.
AB  - BACKGROUND: Asthma is a complex disease that is caused by genetic and
      environmental factors. The production of interleukin (IL)-4, which can influence
      mast cell responsiveness to immunoglobulin (Ig) E--mediated signaling, could be
      modified by genetic variants in the IL-4 promoter. OBJECTIVE: To investigate the
      association between the IL-4 and IL-4RA promoter polymorphisms and asthma in a
      sample of Iranian patients. METHODS: We used polymerase chain reaction with
      sequence-specific primers to investigate the allele and genotype frequencies of 2
      polymorphic genes coding for IL-4 and IL-4RA in 59 Iranian patients with asthma
      and 139 healthy controls. RESULTS: The most frequent genotypes in the patient
      group were IL-4TC (-590), IL-4TC (-33), IL-4 GT (-1098), and IL-4RA GA (+1902).
      In contrast, the frequencies of IL-4 CC (-590), IL-4 CC (-33), IL-4TT (-1098),
      and IL-4RAAA (+1902) were significantly lower in the patient group than in the
      control group. The most frequent haplotypes in our patients were IL-4 TCT and GTC
      at positions -1098,-590,-33. The mean total serum IgE level in patients with the
      TTT/GCC genotype was 258.8 IU/mL, which was significantly higher than the 95.4
      IU/mL observed for other genotypes. CONCLUSION: We showed a strong association
      between the polymorphisms of the IL-4 gene promoter at positions -590, -33 and 
      1098 and bronchial asthma. We also demonstrated an association between their
      haplotypes and serum total IgE.

PMID- 20128417
TI  - Contribution of molecular diagnosis of allergy to the management of pediatric
      patients with allergy to pollen.
AB  - BACKGROUND: Component-resolved diagnosis based on recombinant allergens
      facilitates treatment of multiple sensitization and/or crossreactivity in
      allergic patients. OBJECTIVE: To assess the usefulness of molecular diagnosis in
      childhood allergies. METHODS: A total of 162 children aged 4-16 years diagnosed
      with allergic rhinitis or asthma/rhinitis caused by pollen were referred for
      recombinant allergen-based diagnosis in 2006. Specific immunoglobulin (Ig) E
      against pollen allergens and purified recombinant Phleum pratense pollen
      allergens were measured using an in vitro quantitative assay, and considering the
      recombinant allergens Phl p 1+Phl p 5 as P pratense--specific allergens and Phl p
      7+Phl p 12 as cross-reacting allergens. Conditional probability was calculated to
      determine the relationship between values for specific IgE against major
      allergens and those for cross-reacting allergens. RESULTS: Specific IgE
      antibodies against P pratense were detected in 99.4% of serum samples, and cross
      reacting allergens in 46%. Multiple sensitization to pollen was documented in 38%
      of patients, with Plantago lanceolata as the main cause. Conditional probability
      calculations showed that patients with specific IgE values of 75-80 kU(A)/L to
      Phl p 1+Phl p 5 were 75% (95% confidence interval) more likely to present values
      > or = 2 kUA/L to Phl p 7+Phl p 12. CONCLUSIONS: Our results show that
      recombinant DNA technology can help diagnose allergy in cases of multiple
      sensitization and crossreactivity, and is therefore a promising option for
      improving prognosis and management of allergic pediatric populations.

PMID- 20128418
TI  - Diagnosis of aspirin-induced asthma combining the bronchial and the oral
      challenge tests: a pilot study.
AB  - BACKGROUND: We investigated the usefulness of the bronchial challenge (BC) with
      lysine-acetylsalicylate (L-ASA) in the diagnosis of aspirin-exacerbated
      respiratory disease (AERD) using a protocol that combined both the oral challenge
      (OC) and the BC tests. METHODS: Adult asthmatic patients with suspected AERD who
      underwent BC with L-ASA were included in the study. If the BC result with L-ASA
      was negative, an OC was carried out to establish the diagnosis. AERD was ruled
      out if both the BC and the OC results were negative (nonresponders). Both
      responders and nonresponders were compared for age, gender, a personal or family
      history of atopy, underlying disease, current asthma treatment, and presence of
      nasal polyps. Six patients with asthma but no suggestive history of AERD were
      included as controls. RESULTS: Twenty-two patients completed the study. Ten
      patients tested positive to the BC and/or OC (responders), whereas 12 did not
      (nonresponders). Seven out of the 10 responders had a positive BC result and 3 a
      positive OC result. After BC, 4 patients had an early asthmatic response, 1 had a
      dual response, and 2 had isolated late responses. No significant differences were
      observed in the aforementioned variables between responders and nonresponders.
      The results of both challenges were negative in the 6 controls. CONCLUSIONS: The
      BC had a high positive predictive value, was safe, and when negative, the
      subsequent OC did not result in any severe adverse reactions. The BC elicited an
      isolated late asthmatic response that has not been previously described in the
      literature.

PMID- 20128419
TI  - 5-Lipoxygenase pathway gene polymorphisms: lack of association with asthma in a
      Spanish population.
AB  - BACKGROUND: Cysteinyl-leukotrienes are mediators of inflammatory responses in
      bronchial asthma. We studied the genes encoding the enzymes involved in their
      synthesis to identify risk factors for asthma. The promoter polymorphisms LTC4S 
      444 A/C, ALOX5 -176/-147, and ALOX5AP -169/-146 have been reported to be
      associated with bronchial asthma. METHODS: We analyzed the effects of LTC4S -444
      A/C, ALOX5 -176/-147, and ALOX5AP -169/-146 on asthma susceptibility by means of
      a case-control study with 193 ethnically matched, unrelated individuals.
      Participants were classified as severe asthmatics, nonsevere asthmatics, and
      nonasthmatics, using a combination of 2 techniques: polymerase chain reaction
      restricted fragment length polymorphism and multiplex capillary electrophoresis.
      RESULTS: No association was found between these polymorphisms and asthma, neither
      individually nor in combination. CONCLUSION: Although the studied polymorphisms
      have been previously reported to constitute risk factors for the disease, we
      found no association between LTC4S -444 A/C, ALOX5 -176/-147, and ALOX5AP -169/
      146 polymorphisms and bronchial asthma.

PMID- 20128420
TI  - Effects of fexofenadine on inflammatory mediators in nasal lavage fluid in
      intermittent allergic rhinitis.
AB  - OBJECTIVE: Allergic rhinitis, a disease that impairs quality of life, is
      characterized by inflammation due to an allergic reaction. Fexofenadine is a
      second-generation histamine receptor blocker well known for its potent
      interaction with this inflammatory process. The main aim of this study was to
      further clarify the anti-inflammatory effects exerted by fexofenadine in patients
      with intermittent allergic rhinitis. METHODS: Twenty patients with intermittent
      allergic rhinitis due to birch and mugwort pollen were enrolled. Fexofenadine was
      administered once a day at a dose of 120 mg. Clinical improvement was assessed by
      a symptom score, and nasal airway flows were measured by anterior rhinomanometry
      at baseline and after 2 weeks of treatment with fexofenadine. Nasal smears were
      tested for eosinophils and nasal lavage fluid were examined for histamine,
      cysteinyl leukotrienes, soluble intercellular adhesion molecule-1, eosinophil
      cationic protein, and albumin by enzyme-linked immunosorbent assay. All the tests
      were performed during the pollen season. RESULTS: Fexofenadine induced a
      significant improvement in nasal and ocular symptoms (P < .001), nasal edema and
      secretion (P < .001), and nasal airway flow (P < .001). The clinical improvement
      was related to a significant reduction in all inflammatory mediators (P < .01 in
      all cases). CONCLUSION: This study demonstrates that fexofenadine is able to
      mediate significant changes in different nasal lavage markers from patients with
      intermittent allergic rhinitis. The changes observed in the markers analyzed in
      both nasal secretions and serum are attributable to the anti-inflammatory effects
      of fexofenadine in vivo.

PMID- 20128421
TI  - A new variant of the basophil activation test for allergen-induced basophil CD63
      upregulation. The effect of cetirizine.
AB  - OBJECTIVE: The aim of our study was to determine the diagnostic usefulness of a
      newly developed basophil activation test (BAT) in patients allergic to
      Dermatophagoides pteronyssinus and pollens. We also analyzed the influence of
      cetirizine on CD63 upregulation. This popular antihistamine strongly inhibits
      skin tests, but its impact on BAT sensitivity remains unknown and deserves at
      least preliminary determination. METHODS: The study sample comprised 22 patients
      allergic to house dust mite and pollens and 19 healthy controls. All participants
      underwent skin prick testing and the newly developed flow-cytometric basophil
      activation test. The protocol for allergen-induced basophil CD63 upregulation
      consisted of whole blood samples that were processed and stained with anti
      CCR3/CD63 antibodies added to the buffer at the beginning of stimulation. Skin
      prick tests and BAT were performed twice--before and 2 hours after ingestion of
      10 mg of cetirizine. RESULTS: The new BAT is characterized by its short
      processing time, easy basophil gating, and strong CD63 upregulation with very
      high sensitivity and excellent specificity. Our results suggest that allergen
      induced CD63 upregulation by higher doses of allergens is not inhibited 2 hours
      after administration of cetirizine (unlike skin prick tests). CONCLUSION: The BAT
      is a very useful and precise method for the diagnosis of allergy to
      aeroallergens. It is not influenced by cetirizine.

PMID- 20128422
TI  - Prevalence of self reported allergic rhinitis and its relationship with asthma
      among adult Nigerians.
AB  - OBJECTIVES: The aims of the study were to establish the prevalence of self
      reported allergic rhinitis in an adult Nigerian population and to examine the
      relationship between asthma and allergic rhinitis. METHODS: We conducted an
      epidemiological study of adults aged between 18 and 45 years in Ilorin, Nigeria
      from 2005 to 2006. An adaptation of the European Community Respiratory Health
      Survey questionnaire was administered by trained assistants to obtain information
      on demographics, history of nasal allergies, asthma symptoms, and smoking
      history. The participants also underwent spirometry. RESULTS: Of the 761
      individuals screened, 733 were recruited, giving a participation rate of 96.3%;
      441 (60.2%) were men and 292 (39.8%) were women. The prevalence of allergic
      rhinitis and asthma was 29.6% (n = 217) and 14.7% (n = 108), respectively. Of the
      individuals with allergic rhinitis, 31.8% (n = 69) had asthma and of those with
      asthma, 63.9% (n = 69) had allergic rhinitis. The mean (SD) age of those with
      allergic rhinitis was 31 (7.5) years and 65% (n = 141) were men. The determinants
      of asthma in individuals with allergic rhinitis were a family history of asthma
      (odds ratio [OR], 3.38), a history of smoking (OR, -2.58), high socioeconomic
      status (OR, 3.82) obesity (OR, 3.32), and wheezing (OR, 250). Lung volumes were
      reduced in those with both asthma and allergic rhinitis compared to those with
      allergic rhinitis alone. CONCLUSION: Our study revealed a high prevalence of
      allergic rhinitis in individuals with asthma. It is therefore important to
      increase awareness of the existence of allergic rhinitis and asthma as a common
      airway disease to ensure adequate management and control of both conditions.

PMID- 20128423
TI  - Stress-related maternal factors during pregnancy in relation to childhood eczema:
      results from the LISA Study.
AB  - BACKGROUND: Stress has been suggested to impact the onset and exacerbation of
      eczema and other atopic disorders. Whether early exposure to stress-related
      factors might exert long-term effects remains to be clarified. OBJECTIVE: The
      objective of this study was to investigate whether stress-related maternal
      factors during pregnancy are associated with childhood eczema during the first 6
      years of life. METHODS: Data from 3004 children from a prospective German birth
      cohort study (LISA) were analyzed. Information from maternity certificates and
      questionnaire information on unwanted pregnancy were used to evaluate stress
      related maternal factors during pregnancy. Prevalence data for physician
      diagnosed eczema were available up to the age of 6 years. RESULTS: Maternal
      factors during pregnancy were positively associated with childhood eczema in
      terms of cumulative prevalence up to the age of 2 years (adjusted odds ratio,
      1.48; 95% confidence interval, 0.95-2.30) after adjusting for potential
      confounders. Beyond the second year no increased risk was observed. CONCLUSIONS:
      The results of this study suggest that stress-related maternal factors during
      pregnancy are associated with an increased risk of childhood eczema during the
      first 2 years of life. The impact of postnatal stress such as parental divorce or
      separation on this association could not be clarified. Future studies should
      therefore further elucidate how prenatal and postnatal stress interact and
      whether prenatal stress might have a programming effect. If future studies
      confirm the findings of this study, reducing maternal stress during pregnancy
      might be a possible target in the primary prevention of eczema during childhood.

PMID- 20128424
TI  - Reduction of nasal volume after allergen-induced rhinitis in patients treated
      with rupatadine: a randomized, cross-over, double-blind, placebo-controlled
      study.
AB  - OBJECTIVE: To measure the reduction in nasal obstruction using acoustic
      rhinometry in patients with allergic rhinitis treated with rupatadine. METHODS:
      We performed a randomized, double-blind, cross-over, placebo-controlled clinical
      trial in asymptomatic patients with allergic rhinitis. Patients received
      rupatadine 10 mg or placebo once daily for 3 days, in 2 subsequent periods
      separated by a washout interval of 14 days. We performed a nasal allergen
      challenge during each period, and measured nasal volume using acoustic rhinometry
      and nasal nitric oxide (nNO) at baseline, and at 2 hours and 24 hours after the
      challenge. We also evaluated nasal symptoms (rhinorrhea, itching, obstruction,
      and sneezing), as well as total symptom score (T4SS) at the same time points as
      for the primary objective. RESULTS: The study population comprised 30 outpatients
      with a mean (SD) age of 28 (10) years. Nasal airway blockage was significantly
      lower in the rupatadine group than in the placebo group (47%, P < .05) at 2 hours
      postchallenge. nNO in the rupatadine-treated patients remained unaltered, unlike
      in the placebo-treated group, where levels decreased at 2 hours. After treatment
      with rupatadine, patients showed a lower decrease in the mean total symptoms
      score at 2 hours (3.6 [2.6]) compared with placebo (3.9 [2.9]), although these
      differences did not achieve statistical significance. Overall, rupatadine was
      well tolerated and no serious or unexpected adverse events were observed.
      CONCLUSIONS: Rupatadine 10 mg can reduce nasal obstruction assessed by objective
      measures and is well tolerated in patients with allergic rhinitis.

PMID- 20128425
TI  - Novel RAG2 mutation in a patient with T- B- severe combined immunodeficiency and
      disseminated BCG disease.
AB  - T-B-NK+ severe combined immunodeficiency (SCID) is an autosomal recessive disease
      that is caused mainly by a defect in the recombination activating genes (RAG).
      Patients with SCID usually experience life-threatening opportunistic infections
      in early infancy and complications after vaccination with bacille Calmette-Guerin
      (BCG). We report a patient of consanguineous parents who was referred to our
      center with subaxillary lymphadenitis and respiratory distress. Laboratory
      studies confirmed the diagnosis of T-B-NK+ SCID and molecular studies revealed
      homozygous mutations in the RAG2 gene. The patient died despite administration of
      antituberculosis drugs, antibiotics, and intravenous immunoglobulin. Inoculation
      of live vaccines such as BCG should be postponed in families with a positive
      history of SCID until screening tests rule out this condition.

PMID- 20128426
TI  - Food allergy due to olive.
AB  - We report the case of a 28-year-old man who presented palatal itching and
      genaralized urticaria following ingestion of olive 3 years after being diagnosed
      with olive pollinosis. The patient did not have a history of food allergy or
      urticaria. The results of skin prick tests with aeroallergens including latex
      were positive for house dust mite and olive pollen. The results of prick tests
      and prick-to-prick tests for olive fruit were positive, as were those of specific
      immunoglobulin E tests to olive pollen and fruit. The results of prick tests to
      peach, pear, kiwi, melon, and nut were negative. Nasal provocation with olive
      pollen gave positive results. An open oral provocation test with olive oil did
      not cause symptoms. This case is unique in that the patient developed olive fruit
      allergy in the presence of olive pollinosis, and he did not experience allergic
      symptoms to fruits other than olive, thus enabling us to define a new pollen-food
      (olive-olive) syndrome.

PMID- 20128427
TI  - Severe congenital neutropenia in 2 siblings of consanguineous parents. The role
      of HAX1 deficiency.
AB  - Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease
      that is characterized by persistent severe neutropenia and severe early-onset
      bacterial infections. We report the case of 2 siblings with SCN who were the
      children of consanguineous parents. The HAX1 mutation was identified in both
      siblings. Both patients suffered from oral ulcers, candidiasis, respiratory tract
      infections, and diarrhea. A bone marrow biopsy, performed to determine the cause
      of their persistent severe neutropenia, revealed myeloid maturation arrest; thus
      confirming the diagnosis of SCN. Granulocyte colony-stimulating factor and
      prophylactic antibiotics were started. A molecular study revealed a homozygous
      W44X mutation of the HAX1 gene in both cases. HAX1 deficiency should be
      considered in any child with severe infections and neutropenia, especially in
      children of consanguineous parents. Early diagnosis and appropriate treatment
      could prevent complications in this group of patients.

PMID- 20128428
TI  - Identification of 2 new allergens of Phoenix dactylifera using an
      immunoproteomics approach.
AB  - The date palm (Phoenix dactylifera) has a wide geographical distribution (Middle
      East, Mediterranean, central Africa, western Asia, Australia, and North America).
      Pho d 2, the major allergen of date palm pollen was recently identified as a
      profilin, yet little is known about the nature of the other pollen allergens from
      this tree. The objective of this study was to characterize clinically significant
      allergens other than profilins from P. dactylifera pollen using immunoproteomics.
      In order to reveal the proteins causing the allergy, we used serum from a patient
      monosensitized to date palm pollen extract who experienced asthma and
      rhinoconjunctivitis during the palm tree pollen season. The results revealed 2
      novel immunoglobulin E-binding proteins not related to the cross-reactive
      allergen profilin. Individualized allergens of Pdactylifera that cause specific
      date palm pollen sensitization must be defined to determine the real prevalence
      of sensitization to this species.

PMID- 20128429
TI  - Dose-dependent anaphylaxis to orange juice without detectable specific
      immunoglobulin E.

PMID- 20128431
TI  - Contact dermatitis to antibiotic ointments.

PMID- 20128430
TI  - Sclerosing cholangitis associated with good syndrome.

PMID- 20128432
TI  - Thrombocytopenia and iodinated contrast.

PMID- 20128433
TI  - Simultaneous SCIT with 2 separate allergen extracts demonstrates comparable
      safety compared to SCIT with a single allergen extract.

PMID- 20128434
TI  - Recent-onset bronchial asthma as a manifestation of systemic mastocytosis.

PMID- 20128435
TI  - Immunoglobulin E reactivity to nOle e 1 as a diagnostic marker of allergy to Olea
      europaea pollen.

PMID- 20128436
TI  - Fungal colonization in nasal polyposis.

PMID- 20128437
TI  - Molecular cloning of the first human monoclonal antibodies neutralizing with high
      potency swine-origin influenza A pandemic virus (S-OIV).
AB  - The pandemic caused by the new H1N1 swine-origin influenza virus (S-OIV) strain
      is a worldwide health emergency and alternative therapeutic and prophylactic
      options are greatly needed. Two human monoclonal antibody Fab fragments (HMab)
      neutralizing the novel H1N1 influenza strain at very low concentrations were
      cloned from a patient who had a broad-range anti-H1N1 serum neutralizing
      activity. The two HMabs neutralized S-OIV with an IC50 of 2.8 and 4 microg/mL.
      The genes coding for the neutralizing HMabs could be used for generating full
      human monoclonal IgGs that can be safely administered with the potentially of
      representing a novel drug to be used in the prophylaxis and the treatment of this
      human infection. This is the first report of molecular cloning of human
      monoclonal antibodies against the new pandemic swine-origin influenza virus.

PMID- 20128438
TI  - Human immunodeficiency virus type 1 intersubtype recombinants predominate in the
      AIDS epidemic in Cameroon.
AB  - A broad and rapidly changing HIV Type 1 (HIV-1) diversity has been reported from
      different populations in Cameroon since the early epidemic. Our understanding of
      HIV-1 dynamics can be improved by a systematic surveillance in Cameroon as
      accessibility and use of antiretroviral drugs increase. To contribute to this, we
      genotyped 30 samples by sequencing the protease and reverse transcriptase (proRT)
      genes of HIV-1. Phylogenetic analysis of the HIV-1 proRT sequences using the
      MEGA3 software showed that 26 (86.7%) were recombinant forms which included 20
      (66.7%) circulating recombinant forms: CRF02_AG, (50%), CRF06_cpx (3.3%), CRF11
      _cpx (10%) and CRF37_cpx (3.3%), and 6 unique recombinant forms (URF, 20%). Two
      of the six URFs were second generation recombinants and 4 contained unclassified
      segments. HIV-1 subtypes A1 (3.3%), C (3.3%) and D (6.7%) were also identified.
      Although partial sequences of HIV-1 genome were analysed, our results indicate
      that recombinant HIV-1 variants predominate in the AIDS epidemic in Cameroon.
      With the widespread use of antiretroviral drugs in Cameroon and the circulation
      of several HIV-1 variants within this population, the emergence of recombinants
      with unknown diagnostic and clinical consequences is a concern.

PMID- 20128439
TI  - Diagnosis of neurological herpesvirus infections: real time PCR in cerebral
      spinal fluid analysis.
AB  - Human herpesviruses (HHVs) cause many serious acute and persistent central
      nervous system (CNS) disorders. Because these infections manifest with various,
      often non-specific, symptoms and signs, and because specific therapy is often
      available, accurate diagnosis is essential. Cerebrospinal fluid (CSF) from 146
      patients with acute meningitis or meningoencephalitis and 9 with "other
      neurological disorders" were analyzed by using an automatic system for nucleic
      acid extraction and quantitative real-time polymerase chain reaction (PCR) for
      herpes simplex 1 and 2 (HSV-1, HSV-2), Epstein-Barr virus (EBV), human
      cytomegalovirus (HCMV), herpesvirus-6 (HHV-6), and varicella-zoster virus (VZV).
      HHVs DNA was detected in 52 of 155 (33.5%) analyzed samples. In 39 CSF samples
      from patients with meningoencephalitis we found: VZV in 13, HSV-1 in 12, EBV in
      6, HHV-6 in 4, and HSV-2 in 4. Co-infections of EBV and HSV-2, HSV-1 and HSV-2,
      HSV-1 and VZV were also disclosed in four cases. In addition, two patients with
      Guillain-Barre syndrome had HCMV and one showed HHV6 positivity, two patients
      with myelitis / polymyeloradiculitis had VZV and HCMV respectively, HHV-6 DNA was
      found in one patient with lateral amyotrophic sclerosis. Three CSF specimens from
      HIV-infected patients with CNS complications had HHV-6 or EBV DNA. Moreover
      quantitative data were also correlated to clinical conditions to obtain more
      information on the virus aetiopathogenic role.

PMID- 20128440
TI  - Human antibodies from phage display libraries: expression of recombinant full
      length immunoglobulin G specific to the hepatitis C virus E2 glycoprotein.
AB  - Evidence from clinical and experimental studies indicates that hepatitis C virus
      E2 glycoprotein (HCV/E2) represents a major target antigen involved in the
      containment and resolution of naturally occurring HCV infection. Antibody phage
      display allows the molecular cloning of cDNA sequences encoding antibody
      fragments specific to a wide range of diverse antigens. These antibodies may be
      produced in bacteria as Fab or converted into full length IgG. The latter have a
      higher serum half life and display Fc encoded function. Using a library prepared
      from an HCV-infected individual, we selected a panel of Fab fragments for binding
      to invariant epitopes of the E2 glycoprotein. This work describes a technique
      used to convert the selected Fab fragments into full length IgG and to express
      these antibodies in eukaryotic cells. All the recombinant antibodies retained the
      binding specificity of the parental Fab showing an increase in apparent relative
      affinity for E2.

PMID- 20128441
TI  - Detection of 14 human papillomavirus genotypes in cervical samples in women from
      a central-southern area of Italy showing different Pap test results.
AB  - We evaluated the prevalence of human papillomavirus (HPV) infection and
      correlated the molecular test results with the cytological examination data (PAP
      test) in 364 women living in central-southern Italy (Molise region), by means of
      polymerase chain reaction HPV DNA genotyping and of cervical cytology. One
      hundred and twenty-eight women resulted HPV positive (35.2%), HPV16 being the
      most frequent genotype. HPV positive women were significantly younger than
      negative patients (35.9 +/- 8.4 years and 38.2 +/- 9.1, respectively; p = 0.018);
      women with multiple infections were also significantly younger than those with
      single infection (31.7 +/- 6.9 and 37.6 +/- 8.3, respectively; p = 0.0002).
      Moreover, high risk HPV positive patients were significantly younger than low
      risk HPV positive women (35.1 +/- 7.7 and 40.5 +/- 10.5, respectively; p =
      0.008). In the HPV positive group, 14 patients (10.9%) did not show any
      significant cytological alteration. Conversely, 7 out of 236 HPV negative women
      (3.0%) showed high grade squamous intraepithelial lesions (HSIL). Furthermore,
      HPV 16 or 18 were present in more than 70% of women positive for HSIL at
      cytology. Our data suggest the potential effectiveness of combined cytology and
      molecular test for further study of clinical cases with apparently laboratory
      conflicting results.

PMID- 20128442
TI  - Case definition for Ebola and Marburg haemorrhagic fevers: a complex challenge
      for epidemiologists and clinicians.
AB  - Viral haemorrhagic fevers (VHFs) represent a challenge for public health because
      of their epidemic potential, and their possible use as bioterrorism agents poses
      particular concern. In 1999 the World Health Organization (WHO) proposed a case
      definition for VHFs, subsequently adopted by other international institutions
      with the aim of early detection of initial cases/outbreaks in western countries.
      We applied this case definition to reports of Ebola and Marburg virus infections
      to estimate its sensitivity to detect cases of the disease. We analyzed clinical
      descriptions of 795 reported cases of Ebola haemorrhagic fever: only 58.5% of
      patients met the proposed case definition. A similar figure was obtained
      reviewing 169 cases of Marburg diseases, of which only 64.5% were in accordance
      with the case definition. In conclusion, the WHO case definition for hemorrhagic
      fevers is too specific and has poor sensitivity both for case finding during
      Ebola or Marburg outbreaks, and for early detection of suspected cases in western
      countries. It can lead to a hazardous number of false negatives and its use
      should be discouraged for early detection of cases.

PMID- 20128443
TI  - QuantiFERON-TB Gold In-Tube test (QFT-GIT) for the screening of latent
      tuberculosis in recent immigrants to Italy.
AB  - To evaluate the agreement between QuantiFERON-TB Gold In-Tube test (QFT-GIT) and
      tuberculin skin test (TST) for the screening of latent tuberculosis infection
      (LTBI) in recent immigrants to Italy, 279 subjects were submitted to concomitant
      TST and QFT-GIT. The agreement was analyzed using k statistics. A total of 72/279
      (25.8%) individuals were TST positive, while 107/279 (38.3%) were QFT-GIT
      positive. The overall agreement between QFT-GIT and TST was 70.9%, with k
      statistic of 0.35. Using different TST and QFT-GIT cut-offs, the best concordance
      value was obtained for QFT-GIT at > 2.64 IU/ml and TST at > 10mm (k = 0.409).
      Discordant results were found for 58 subjects (21%) with QFT-GIT positive/TST
      negative and 23 (8%) with QFT-GIT negative/TST positive. A high amount of
      discordance QFT-GIT+/TST- was described. QFT-GIT might increase the
      identification of LTBI cases among recent immigrants.

PMID- 20128444
TI  - Highly sensitive detection of Shigella flexneri using fluorescent silica
      nanoparticles.
AB  - Robust signal amplification tactic is a good solution for improving detection
      sensitivity. Unprocessed fluorophores have many limitations. Here we describe an
      effective strategy for highly sensitive detection of bacteria by using
      fluorescent conjugated nanoparticles. The nanoparticles were synthesized using
      silica as matrix. Fluorescein isothiocyanate distributed in the matrix. S.
      flexneri specific antibody was coated on the surface of the nanoparticles.
      Compared to the traditional fluorescent antibody, these antibody-coated
      fluorescent conjugated nanoparticles were resistant to photobleaching and could
      ensure prolonged microscope checking for a small number of target bacteria. These
      nanoparticles could be used in routine bacterial detection for different species.

PMID- 20128445
TI  - In vitro evaluation of the antibacterial activity of cured dentin/enamel adhesive
      incorporating the antimicrobial agent MDPB.
AB  - The aim of this study was to investigate in vitro the antibacterial effect of a
      dentin/enamel adhesive containing MDPB (Clearfil Protect Bond) after curing and
      to compare it with an adhesive not containing MDPB (Clearfil SE Bond). The
      antibacterial effect of the cured adhesives was tested on Enterococcus faecalis
      by the evaluation of growth inhibition in a 48-h microplate direct contact test
      (DCT). The presence of antibacterial activity due to soluble components was also
      investigated by an agar diffusion test (ADT) performed with the adhesives cured
      on the surface of dentin disks. In the DCT, both the tested materials showed
      complete inhibition of bacterial growth until the 7-h reading, regardless of
      whether direct contact with the bacterial inoculum was continued or limited to 1
      h. Stationary growth phase turbidity levels were observed at 24 or 48-h
      incubation. The ADT produced no inhibition areas around the dentin disks. Both
      adhesives tested in vitro under conditions simulating those encountered in the
      restorative treatment of dental caries were equally able to delay bacterial
      growth demonstrating a similar bacteriostatic effect. As suggested by both the
      DCT and the ADT, the antibacterial effect of the two adhesives depends on direct
      contact and does not seem to be related to the diffusion of soluble components.

PMID- 20128446
TI  - Offer of rapid testing and alternative biological samples as practical tools to
      implement HIV screening programs.
AB  - Implementation of HIV testing has the objective to increase screening, identify
      and counsel persons with infection, link them to clinical services and reduce
      transmission. Rapid tests and/or alternative biological samples (like oral fluid)
      give the option for a better general consent in approaching screening, immediate
      referral of HIV positives to medical treatment and partner notification. We
      tested the performance characteristics of an oral fluid-based rapid HIV test
      (Rapidtest HIV lateral flow-Healthchem diag. LLC) in comparison with routinely
      utilized methods in a selected population of known positive (N = 121) or negative
      (N = 754) subjects. The sensitivity of the rapid test was 99.1% (one false
      negative sample) and the specificity 98.8%. Five negatives showed a faint
      reactivity, 3 of these were reactive also in the reference test, one with a p24
      only reaction in Western blot. If these 3 samples were excluded from the analysis
      the specificity increases to 99.2%. Results from our study confirm that, although
      a continuous improvement of the test performance is still needed to minimize
      false negative and positive results, rapid test and alternative biological
      samples may contribute to HIV prevention strategies by reaching a larger
      population particularly when and where regular screening procedures are difficult
      to obtain.

PMID- 20128447
TI  - Phylogenetic analysis of the surface proteins of influenza A (H5N1) viruses
      isolated in Asian and African populations.
AB  - Highly pathogenic H5N1 virus can infect a variety of animals and continually
      poses a threat to animal and human health. Here, phylogenetic analysis of the
      hemagglutinin and neuraminidase genes indicated that the hemagglutinin gene of
      all human isolates, although very similar to each other, fell within different
      clades corresponding to antigenically distinguishable variants. Likewise, the N1
      neuraminidase gene forms a clade that is evolutionarily distinct from previously
      characterized N1 neuraminidases. So, although all H5N1 viruses were derived from
      ancestors circulating in south-east Asia more than ten years ago, since 2003 they
      have evolved into geographically distinct groups within each country.

PMID- 20128448
TI  - Surveillance of influenza virus B circulation in Northern Italy: summer-fall 2008
      isolation of three strains and phylogenetic analysis.
AB  - Influenza virus type B strains were unexpectedly detected and isolated in Italy
      during summer-fall 2008 from three patients travelling to Italy from Lebanon,
      Senegal and Uzbekistan. The three summer-fall strains matched to a high degree
      the hemagglutinin (HA1) of influenza virus type B strains circulating in Italy in
      the second part (January through April) of the 2007/2008 season, and HA1 of the
      type B strains included in the 2008/2009 vaccine (B/Yamagata/16/88 lineage).
      Surveillance of influenza virus circulation in Western countries also during the
      summer-fall season may help to trace and anticipate the appearance of new
      influenza virus variants.

PMID- 20128449
TI  - Thymidine kinase and deoxycytidine kinase in HIV-infected children.
AB  - It has been demonstrated that HIV infection may affect the levels of thymidine
      kinase (TK) and deoxycytidine kinase (dCK) in peripheral blood mononuclear cells
      from HIV infected adults. The aim of this study was to examine the effect of HIV
      infection and/or antiretroviral therapy on the activity of the above enzymes in
      HIV-infected children. The results showed that an inter-individual variability in
      TK and dCK activities does exist in both HIV infected and uninfected children. TK
      and dCK levels in PBMC from HIV infected and non infected children did not
      significantly differ. Furthermore, the therapeutic regimen, including zidovudine,
      does not seem to affect TK activity.

PMID- 20128451
TI  - Critical questions for veterinary education on global veterinary public health.

PMID- 20128450
TI  - Mycobacterium xenopi pulmonary infection resulting in self-limited immune
      reconstitution inflammatory syndrome in an HIV-1 infected patient.
AB  - Highly active antiretroviral therapy (HAART) has been shown to induce a major and
      durable viral load reduction accompanied by a stable CD4 increase. This process
      may evolve with adverse clinical phenomena, known as the immune reconstitution
      inflammatory syndrome (IRIS). In the HIV population, non-tuberculous mycobacteria
      are a common cause of IRIS. However, only a few cases of Mycobacterium xenopi
      associated IRIS have been described. This paper concerns a case of M. xenopi
      pulmonary infection resulting in self-limited immune reconstitution inflammatory
      syndrome in an HIV-1 infected patient.

PMID- 20128452
TI  - Accomplishing essential curricular change.

PMID- 20128453
TI  - One world of veterinary medicine.
AB  - The veterinary profession finds itself in the midst of a new world order. Today
      veterinarians are part of a world that is exquisitely interconnected culturally,
      economically, socially, and professionally. As a consequence, societal needs and
      expectations of the profession are more demanding, critical and far-reaching.
      Veterinarians must play important roles in five intersecting domains of work:
      public health, bio-medical research, global food safety and security, ecosystem
      health and the more traditional role of caring for animals. To be successful in
      this broad and complex range of services and activities, veterinarians must
      possess an expanded knowledge base, acquire new skills, and develop a new mindset
      that will ensure their success and excellence in all these domains. The
      veterinary profession is becoming more fragmented and specialised, and it needs
      to be brought back together by a single sphere of knowledge or discipline that
      can serve as an intellectual foundation. The concept of One World of Veterinary
      Medicine can do just that. With this mindset veterinarians will become better
      connected to the world around and gain new public recognition and esteem. To
      achieve this, a special commitment by academic veterinary medicine is, of course,
      essential. Veterinary schools must lead an educational transformation that
      reaffirms the social contract of veterinarians and works to align diverse
      sectors, build a global community, find a common purpose and expand the 21st
      Century veterinary portfolio of services, activities, and new possibilities.

PMID- 20128454
TI  - One world--one medicine--one health: emerging veterinary challenges and
      opportunities.
AB  - The interdependence of humans, animals, and their environment has never been more
      important than now. The most prominent issues putting pressure on global health
      today include the dramatic emergence and spread of zoonotic diseases,
      contamination of food, water and soil, bioterrorist events, and degradation of
      resources and habitats. Current global health challenges have prompted a call for
      more holistic, collaborative, action-oriented approaches toward the goal of
      logical and practical solutions. Veterinarians have pivotal obligations,
      opportunities, and contributions to make in enhancing public health, recognising
      and responding to zoonotic disease transmission, maintaining food and water
      quality, and promoting wildlife and ecosystem health.

PMID- 20128455
TI  - The responsibilities of veterinary educators in responding to emerging needs in
      veterinary medicine.
AB  - It is an unfortunate fact that not only has veterinary education failed to adapt
      in the face of likely future needs, but it has also failed to respond to societal
      changes that have already taken place and that have affected the requirements for
      veterinary services and veterinary capability. The responsibility is primarily
      that of educators, although vision and foresight require a co-ordinated approach
      involving national and international veterinary organisations. Once it is
      accepted by all parties that change is essential, the implementation will fail
      unless there is a unified programme involving the schools and colleges, the
      accrediting agencies, the licensing authorities, governments, the professional
      organisations and corporate veterinary medicine. All have a role to play, and any
      one can readily block progress. A unified approach is an absolute requirement.
      The developed countries must take a leading role, but the issues are global, and
      ways must be found to facilitate change in all parts of the world. Disease knows
      no boundaries, and any strategy is only as strong as its weakest link.

PMID- 20128456
TI  - Essential veterinary education in food safety, food hygiene and biosecurity: a
      global perspective.
AB  - A big challenge for veterinary educators is to stimulate interest in public
      health medicine and make the curriculum interesting, and relevant, to veterinary
      students. Veterinary public health encompasses many areas, including zoonosis
      control, food safety, animal health and biosecurity, animals as sentinels of
      environmental hazards and the contribution of animal waste to pollution of food
      and water, so there is no shortage of ammunition for the veterinary educator in
      the competition for students' attention. Veterinary educators, not the students,
      will have failed if graduates complete their studies without being convinced of
      the importance and relevance of veterinary public health.

PMID- 20128457
TI  - The role and mandate of the World Organisation for Animal Health in veterinary
      education.
AB  - The World Organisation for Animal Health (OIE), which was created in 1924 under
      the name Office International des Epizooties, is in charge of setting
      international standards and guidelines for animal health and welfare. The
      original aim of the Organisation was to control the international spread of
      infectious animal diseases, but this aim has expanded over the years and now the
      OIE has a global mandate to 'improve animal health worldwide' for both
      terrestrial and aquatic animals. A vital factor in successfully fulfilling this
      mandate is the quality and performance of both the public and private components
      of national Veterinary Services, which are increasingly working at the interface
      between human, animal and environmental health. The OIE considers global
      veterinary education to be key in maintaining and improving the quality of these
      Veterinary Services. Consequently, the competencies and continuing education of
      veterinarians are a priority in the assessment tool that the Organisation has
      developed to evaluate the performance of Veterinary Services (PVS). Evaluating
      the abilities and training of veterinarians is an important part of a PVS
      evaluation, as well-educated veterinarians with appropriate training are
      essential in improving Veterinary Services worldwide and in helping the OIE to
      fulfil its mandate.

PMID- 20128458
TI  - Veterinary medicine, food security and the global environment.
AB  - The authors focus on the role of veterinary medicine in feeding the nine billion
      people projected to inhabit the planet by 2050, despite the problems of global
      warming, political constraints and environmental destruction. Population growth,
      predominantly urban, will occur mainly in developing countries, at a magnitude
      comparable to creating a city the size of Los Angeles, the second largest city in
      the United States of America, every three weeks for the next 40 years.
      Accompanying this growth will be a greatly increased demand for animal protein.
      How this burgeoning demand can be met by intensive and extensive systems of
      animal production is discussed, with particular reference to the immensely
      important role that the veterinary profession and schools must play.

PMID- 20128459
TI  - Essential veterinary education in the cultural, political and biological
      complexities of international trade in animals and animal products.
AB  - Globalisation has changed the veterinary profession in many ways and academic
      institutes may need to re-tool to help future professionals deal with the changes
      in a successful and productive way. The remarkably expanded and expanding volume
      of trade and traffic in animals and animal products means that to be effective
      veterinarians must grasp some of the complexities inherent in this trade. Being
      able to engage productively in cross-cultural dialogue will be important in
      negotiations over livestock shipments and also within the context of the delivery
      of medical services to companion animals in societies that are becoming
      increasingly diverse. Understanding the political landscapes that influence trade
      decisions will help to expedite agreements and facilitate the transfer of goods
      and materials that involve animal health. Disease emergence will continue to
      occur, and an awareness of the factors responsible and the response measures to
      undertake will help to contain any damage.

PMID- 20128460
TI  - The importance of food animal veterinary education.
AB  - The Bologna Declaration of 19 June 1999 was a pledge, signed by 29 European
      countries, to reform higher education systems in order to create a European Space
      for Higher Education by 2010. As the deadline approaches, it is time to specify
      how the veterinary curricula can most adequately be oriented to adapt to the
      guidelines of the Declaration. The increasing demand for food of animal origin
      has made it clear that there is a lack of farm veterinarians in some western
      countries. Paradoxically, an increasingly 'urban' mentality is developing in the
      profession and in veterinary education. In contrast to what happens in the field
      of companion animals, food animal veterinary education must integrate knowledge
      and practice in animal production with training in health and population
      medicine. However, in order to guarantee safety and food traceability from the
      farm to the fork, priority must first be given to any possible repercussions that
      might arise from public health issues, and then to profitability.

PMID- 20128461
TI  - Essential veterinary education in infectious diseases of livestock and related
      scientific disciplines.
AB  - The World Organisation for Animal Health (commonly referred to bythe acronym of
      its original French name Office International des Epizooties [OIE]) was created
      in 1924 with the aim of controlling the international spread of infectious animal
      diseases. The OIE mandate has broadened since then, but the prevention and
      control of infectious and parasitic diseases are still at the heart of OIE
      activities. To plan and implement effective disease control strategies the
      Veterinary Services of OIE Member Countries need well-educated veterinarians who
      have extensive knowledge of how and why outbreaks of infectious animal diseases
      occur and spread and how they can be prevented and controlled. The teaching of
      fundamental scientific disciplines - virology, bacteriology, parasitology,
      epidemiology, risk analysis, immunology and vaccinology--is therefore a vital
      component of all veterinary education programmes.

PMID- 20128462
TI  - Essential veterinary education in avian medicine: a global perspective.
AB  - Avian medicine is a relatively recent discipline in the veterinary curriculum,
      and is definitely not considered a topical issue. However, in the face of a
      growing demand for poultry meat worldwide, and in view of the health issues
      surrounding wild, exotic and pet birds, the relevance of avian medicine should be
      acknowledged and taken into account when revising curricula.

PMID- 20128463
TI  - Essential veterinary education in fish health and disease: a global perspective.
AB  - Fish are the largest class of vertebrates, with over 25,000 estimated species and
      subspecies. Fish have evolved unique anatomical and physiological adaptations,
      when compared to terrestrial vertebrates, for life in a range of aquatic
      environments. Interest in aquatic animal health has been recorded in Eastern and
      Western cultures for more than 2,000 years. In recent times, there has been an
      increase in the numbers of aquatic animals being used as companion animals or
      pets, for food and in laboratories, as well as in restoration and conservation
      programmes. There has also been a corresponding increase in concern for their
      health and welfare. Moral and ethical considerations require the optimisation of
      husbandry practices and advances in aquatic animal health for these animals. As
      with other vertebrates, veterinarians are best equipped to meet the challenges
      for aquatic animal health from clinical, scientific and legal perspectives. To
      accomplish this goal, veterinary education must incorporate aquatic animal health
      throughout graduate curricula, create advanced postgraduate training
      opportunities, and support a continuum of professional development opportunities
      for all levels of aquatic animal health expertise.

PMID- 20128464
TI  - Essential veterinary education in emerging infections, modes of introduction of
      exotic animals, zoonotic diseases, bioterrorism, implications for human and
      animal health and disease manifestation.
AB  - A fundamental role of the veterinary profession is the protection of human health
      through wholesome food and control of diseases of animal origin, especially
      zoonoses. Therefore, training of veterinary students worldwide needs to face the
      new challenges posed by emerging infections, both from wildlife and domestic
      animals, as well as risks from bio/agroterrorism. New courses emphasising
      recognition, response, recovery and prevention must be developed to respond to
      natural or intentionally induced emerging diseases and zoonoses. Training
      programmes in applied epidemiology, zoonoses and foreign animal diseases are
      crucial for the development of a strong workforce to deal with microbial threats.
      Students should learn the reporting pathways for reportable diseases in their
      countries or states. Knowledge of the principles of ecology and ecosystems should
      be acquired during pre-veterinary studies. Elective classes on wildlife diseases,
      emphasising wildlife zoonotic diseases, should be offered during the veterinary
      curriculum, as well as a course on risk communication, since veterinarians are
      frequently in the position of having to convey complex information under adverse
      circumstances.

PMID- 20128465
TI  - Essential veterinary education in the virology of domestic animals, wild animals
      and birds: diagnosis and pathogenesis of viral infections.
AB  - An education in veterinary virology should establish a basis for life-long
      learning and enable veterinary graduates to address professionally the control
      and eradication of viral diseases, both locally and globally. It is therefore
      more important that the curriculum focuses on a sound understanding of the nature
      and behaviour of viruses and their interactions with animal hosts, rather than
      imparting detailed information on an ever-increasing number of individual viral
      diseases in a widening range of animal species. Graduate veterinarians should be
      prepared with a comprehensive knowledge of the nature of viruses and their close
      dependence on the hosts thatthey infect, as well as a good understanding of
      pathogenesis, immunology, epidemiology, diagnostic approaches and control
      options. All these are necessary if the profession is successfully to meet
      familiar and new challenges in viral diseases in a wide range of host species,
      under different management conditions, in various geographic areas of the world.

PMID- 20128466
TI  - Essential veterinary education on the development of antimicrobial and
      antiparasitic resistance: consequences for animal health and food safety and the
      need for vigilance.
AB  - The role played by the veterinary profession in protecting animal and public
      health, along with food safety, is unique. Thus, it is important that
      veterinarians have the necessary knowledge to be pro-active in responding to the
      emergence of antimicrobial resistance. Many current veterinary educational
      programmes do not attempt to enhance the understanding of undergraduate students
      of this complex situation. As a first step, a modern veterinary education
      programme should provide students with a holistic view of the ecology of
      resistance and clearly describe how antimicrobial resistance emerges.
      Understanding the relationships between drug use, natural selection and
      antimicrobial-resistant organisms, as well as gene mobilisation and
      recombination, and how these contribute to the emergence of resistant organisms
      are important facets of a modern veterinary education.

PMID- 20128467
TI  - Vector-borne diseases.
AB  - Vector-borne diseases have been the scourge of man and animals since the
      beginning of time. Historically, these are the diseases that caused the great
      plagues such as the 'Black Death' in Europe in the 14th Century and the epidemics
      of yellow fever that plagued the development of the New World. Others, such as
      Nagana, contributed to the lack of development in Africa for many years. At the
      turn of the 20th Century, vector-borne diseases were among the most serious
      public and animal health problems in the world. For the most part, these diseases
      were controlled by the middle of the 20th Century through the application of
      knowledge about their natural history along with the judicious use of DDT
      (dichlorodiphenyltrichloroethane) and other residual insecticides to interrupt
      the transmission cycle between arthropod and vertebrate host. However, this
      success initiated a period of complacency in the 1960s and 1970s, which resulted
      in the redirection of resources away from prevention and control of vector-borne
      diseases. The 1970s was also a time in which there were major changes to public
      health policy. Global trends, combined with changes in animal husbandry,
      urbanisation, modern transportation and globalisation, have resulted in a global
      re-emergence of epidemic vector-borne diseases affecting both humans and animals
      over the past 30 years.

PMID- 20128468
TI  - Essential veterinary education in water-borne transmission of disease.
AB  - In this paper, the author reviews the reasons for the current interest in
      waterborne transmission of infectious agents in the veterinary curriculum. In
      addition, the paper provides short summaries of some of the major zoonotic
      outbreaks that have caused this new interest in water-borne diseases. Some
      curricular recommendations are made, including: basic training in modern
      methodologies in microbiology; a brief introduction to water and sewage
      treatment, with some discussion of pathogens in relation to the basic treatment
      processes of flocculation, sedimentation, filtration, disinfection,
      denitrification and phosphorus removal; and an introduction to the regulations
      being promulgated to reduce the pathogen loading of water on farms.

PMID- 20128469
TI  - Essential veterinary education in conservation medicine and ecosystem health: a
      global perspective.
AB  - Conservation medicine is an emerging discipline that links human and animal
      health with ecosystem health and global environmental change. The biosphere is
      threatened by several pervasive and synergistic phenomena that are the result of
      increasing human pressures on the planet: climate change, biological
      impoverishment (loss of biodiversity and ecological processes), emerging
      infectious diseases ('pathogen pollution') and global 'toxification' (pollutants
      such as endocrine-disrupting chemicals). These factors are working in concert to
      diminish human, domestic animal, wildlife and environmental health on this
      planet. By including conservation medicine and ecosystem health into veterinary
      curricula worldwide we can train young veterinarians that will help change
      paradigms and be able to form transdisciplinary teams. These veterinary
      professionals will develop new tools for assessing and monitoring ecological
      health and will be prepared to fulfil critical roles in sustaining global
      ecological health.

PMID- 20128470
TI  - Essential veterinary education in zoological and wildlife medicine: a global
      perspective.
AB  - The current veterinary curriculum leaves graduates ill-equipped for careers in
      the field of zoological and wildlife medicine. Further postgraduate training is
      required to be an effective zoo or wildlife veterinarian. However, whether or not
      students choose to specialise in this field at a later date, the veterinary
      curriculum should cover several issues that are related to wildlife and zoo
      animals, including conservation biology, zoology, behaviour, physiology and
      conservation medicine. These subjects are essential, as we are preparing students
      to work in a world in which there is a global trade in wild animals, an
      increasing number of emerging infectious diseases and numerous environmental
      threats (habitat fragmentation, climate change) linked to anthropogenic change.
      Veterinary students should also be exposed to new opportunities to identify field
      and laboratory tools for the management and possible treatment of diseases in
      captive and wild populations and ecosystems using both in situ and ex situ
      approaches to conservation.

PMID- 20128471
TI  - Essential veterinary education in the welfare of food production animals.
AB  - The primary responsibility of veterinarians is to the animals in their care, so
      veterinary students need to be aware of important issues and factual information
      relevantto animal welfare. Veterinarians have tended to concentrate on physical
      aspects of welfare, but also need to take account of mental aspects (including
      pain) and naturalness. A crucial first step in animal welfare education is to
      encourage students to examine the interactions between welfare science, ethics
      and policy. Scientific measures of welfare include physiological, immunological,
      behavioural, disease and productivity. Welfare ethics includes consideration of
      different ethical theories and of professional ethics. Understanding of policy
      involves awareness of legislation, codes of practice and farm assurance
      programmes. As well as utilising their education in their clinical practice,
      veterinarians may expectto have an important role in influencing policy and
      standards in the wider world. It is recommended that animal welfare should be
      taught as a clearly defined academic subject within the curriculum.

PMID- 20128472
TI  - Essential directions for teaching animal welfare in South America.
AB  - Both the public and the international institutions that regulate the veterinary
      profession have high expectations that veterinarians will understand and take the
      lead in issues of animal welfare. These expectations provide a powerful argument
      for the need to teach animal welfare. The objective of this paper is to share the
      experiences of animal welfare teaching in South America, examining which topics
      seem relevant and why. It builds upon the core international literature on
      teaching animal welfare to veterinary students, highlights priorities learned
      through direct experience of teaching this topic in South America, and has
      benefited from the experiences of other South American animal welfare professors.
      In addition, the authors discuss major challenges in the animal welfare field and
      propose the perceived best strategies. The overall conclusion of the authors is
      that it is not possible to work as a veterinarian and make a valuable
      contribution to society unless the main concepts and issues of animal welfare are
      thoroughly understood and incorporated into practice.

PMID- 20128473
TI  - Preparing for veterinary emergencies: disaster management and the Incident
      Command System.
AB  - An important question that all veterinary schools should consider is whether
      veterinary students should be trained to deal with local or regional states of
      emergency or disasters, such as hurricanes, tornadoes, wildfires, hail and ice
      storms, wind storms, fires, earthquakes, tsunamis, floods and epidemics. When a
      large-scale emergency or disaster does strike, the consequences can be dire for
      the domestic and wild animals of the region and for the humans within the
      vicinity of seriously and painfully injured animals. The authors argue that
      emergency preparedness is essential for the veterinary profession to meet its
      obligations to both animals and humans. The four basic components of disaster
      management are: mitigation, preparedness, response/emergency relief and recovery.

PMID- 20128474
TI  - Essential education in communication skills and cultural sensitivities for global
      public health in an evolving veterinary world.
AB  - In the practise of veterinary medicine and global public health, communication
      skill is as critical as clinical reasoning and an extensive knowledge base.
      Effective communication skills and cross-cultural sensitivity are essential
      across the board for interdisciplinary, international, and local veterinary
      medicine. This paper offers an evidence-based, three-part framework for
      developing and sustaining curricula that enhance communication skills and cross
      cultural sensitivity so that students are better prepared to practise veterinary
      medicine in an evolving world. These curricula may well also serve as a conduit
      for encouraging more veterinary graduates to choose global public health as a
      career path.

PMID- 20128475
TI  - Essential veterinary education in the governance of public Veterinary Services.
AB  - A comprehensive understanding of the national and international governance of
      animal health and Veterinary Services must be part of the professional culture of
      all veterinarians. This includes, in particular, understanding the scope of
      public (government or national) Veterinary Services within the meaning of the
      World Organisation for Animal Health standards, the societal importance of the
      missions of such public Veterinary Services, the history of their structure, and
      their involvement in animal health, animal welfare, essential protein supply,
      etc. The quality standards of a national Veterinary Service must be placed within
      the context of the actual situation in a specific country. Knowing the key
      elements of international governance implies studying the new global context of
      animal health services, the international organisations competent to supervise
      them, and the legal and economic aspects of this arena. In addition, special
      training is recommended for veterinarians recruited by public Veterinary
      Services.

PMID- 20128476
TI  - Essential veterinary education in modern molecular tools for the detection of
      disease: what veterinarians will need to know about genomics and molecular
      biology and diagnostics (including bioterrorist weapons) in 2025.
AB  - Future veterinary education programmes in microbiology will undoubtedly include
      an increasing emphasis on new and existing molecular tools. They should also,
      however, provide veterinarians with a comprehensive and clear understanding of
      the types of results that can be obtained using a particular approach (for
      example, specific diagnostic procedures as against open diagnostic procedures,
      phenotypic versus genotypic characterisation, etc.). Furthermore, students should
      gain a sound knowledge of which type of test is the most appropriate in a given
      clinical or epidemiological situation, and what conclusions can or cannot be
      drawn from the results. Consequently, each veterinary curriculum should focus on
      the following items: the principles of molecular biology and genomics; the
      detection of disease and characteristics of molecular tests; the principles of
      micro-organism taxonomy, sequence comparison and molecular epidemiology and their
      applications (such as: taxonomic identification, epidemiological survey, genetic
      evolution and the traceability of strains); and the role of the veterinarian in
      the field of zoonoses and human public health.

PMID- 20128477
TI  - Essential veterinary education: equipping students with an understanding of the
      need for research in global veterinary public health.
AB  - Research is the foundation of health advancement; therefore, it is imperative
      that all health professionals are well versed in its importance during their
      formal training. Since veterinary education in most countries is now focused on
      preparing clinicians rather than public health practitioners or research
      scientists, educators should recognise the importance of research by emphasising
      the principles and key methodologies that are generic in the life sciences. This
      exposure will provide a baseline understanding for all students, may encourage
      some to complete research projects and research-focused externships during
      school, and will ultimately inspire others to pursue research training after
      graduation. All aspects of veterinary research would benefit from this approach,
      including veterinary public health. This paper discusses the essential
      understanding of research that should be gained through veterinary education,
      particularly within the evolving nature of veterinary public health education.

PMID- 20128478
TI  - Opening the window on public health to veterinary students.
AB  - Veterinary public health is defined by the World Health Organization as: 'the sum
      of all contributions to the physical, mental, and social well-being of humans
      through an understanding and application of veterinary science'. The role of
      animals and wildlife as sources of human diseases continues to increase. As
      demand for public health veterinarians will similarly continue to increase, the
      veterinary profession must make a concentrated effort to encourage veterinary
      students to pursue careers in this field, and increase the opportunities for
      training and experience in this area for both veterinary students and graduates.
      In this paper, the authors describe the existing opportunities for training in or
      practising as a public health veterinarian, with a particular focus on the United
      States of America.

PMID- 20128479
TI  - An essential need: creating opportunities for veterinary students and graduates
      to gain an appreciation of responsibilities and opportunities in global
      veterinary issues.
AB  - Globalisation trends and bioterrorism issues have led to new concerns relating to
      public health, animal health, international trade and food security. There is an
      imperative to internationalise and strengthen global public health capacity by
      renewed emphasis on veterinary public health in veterinary education and
      increasing opportunities for elective experiential learning in public practice
      programmes for veterinary students. Recent experience with a US-Brazil Higher
      Education Consortia Program is used as an example of potential ways in which
      veterinary students can gain an appreciation for global veterinary issues.

PMID- 20128480
TI  - Can curriculum innovations create incentives for young veterinarians to practise
      in remote rural areas?
AB  - Research on the problem of decreasing numbers of rural veterinarians has
      identified that rural practice employment periods following graduation are
      getting shorter and replacing the graduates who leave is becoming increasingly
      difficult. One way of addressing these problems would be to develop a Bachelor of
      Veterinary Science (BVSc) curriculum that motivates young graduates to seek work
      in rural and remote communities and ensures they are more 'practice-ready' as
      soon as they leave university and start working. Developments in a series of
      curriculum initiatives to address this strategy are discussed, including:
      encouraging deeper learning in livestock health and production, provision of
      extramural rotations in rural locations in the final year, offering opportunities
      to study abroad and emphasising the global impact of farm animal medicine,
      developing rural support enhancements for students on rural placements, and
      adjusting admission requirements to increase access for rural students.

PMID- 20128481
TI  - Veterinary school admissions in the United Kingdom: attracting students to
      veterinary careers to meet the expanding needs of the profession and of global
      society.
AB  - Attracting students into a career in global veterinary medicine will be an uphill
      task if effort is focused only on students already at veterinary school. Most
      existing students will have made their career choice at a young age, probably
      based on a perception of the profession as it may have existed decades ago. The
      challenge for veterinary schools in the United Kingdom is to attract a broader
      range of applicants to the veterinary degree courses: applicants who have made a
      positive choice to become veterinarians because of the opportunities a veterinary
      qualification can offer for work in areas such as public health, food safety,
      conservation and global disease control and prevention in an era of climate
      change. This requires proactive recruitment, with careers materials aimed at
      students who may not traditionally have been attracted to the profession. This
      article describes the work that is being undertaken to develop such materials and
      widen access to the profession.

PMID- 20128482
TI  - Integrating the issues of global and veterinary public health into the veterinary
      education curriculum: an Australian perspective.
AB  - This article discusses the integration of global and veterinary public health
      issues into the Australian veterinary curriculum. Formal veterinary education in
      Australia has a history of over 100 years and veterinarians have played a major
      role in the control of zoonotic and transboundary diseases for an even longer
      period. Australia is the largest exporter of red meat and live animals in the
      world. Therefore, educating veterinarians to promote and ensure food safety and
      animal welfare is prominent in Australian veterinary curricula. Veterinary
      degrees are accredited to allow Australian graduates to work professionally
      overseas, including in the United Kingdom and United States of America, and, in
      recent years, globalisation of the student body at Australian veterinary schools
      has occurred. For this reason, an appropriately broad curriculum is required to
      produce graduates who are able to address challenges in veterinary public health
      throughout the world. A Public Health University Network has been established to
      harmonise the veterinary public health curricula at the various veterinary
      schools and to develop the 'Australian veterinary public health philosophy', with
      its links to global issues and the 'One World, One Health' concept. Finally,
      conclusions are drawn on the implications of veterinary public health teaching in
      Australia and the preparation of Australian graduates for the global profession.

PMID- 20128483
TI  - Integrating the issues of world animal health and world public health into the
      veterinary curriculum: a Southeast Asian perspective.
AB  - The authors analysed the curricula of five veterinary schools in Southeast Asia
      to determine how successfully they integrate the issues of global animal health
      and global public health into their programmes. Two schools offer a five-year
      programme while the remaining three offer a six-year programme. The core courses
      within the curricula range from 145 to 224 credit hours, in total. In general,
      world animal health and world public health are well integrated into the
      veterinary curriculum. Most curricula allocate approximately 3% of their total
      credit hours to subjects associated with animal and public health, but other
      subjects that may contain discussions on these issues range between 6% and 10%.
      Most veterinary schools in Southeast Asia offer a Master's programme in
      Veterinary Public Health, with detailed emphasis on animal and public health but
      focusing principally on topics of local importance. At the same time,
      undergraduate and post-graduate veterinary students are exposed to current issues
      in animal and public health through regional and international scientific
      meetings.

PMID- 20128484
TI  - Integrating global animal health, public health and tropical animal health issues
      into the veterinary curriculum: a South African/African perspective.
AB  - The globalisation of trade and food, the increased volume and speed of
      international travel, climate change, and the related escalation of emerging and
      re-emerging infectious diseases mean that countries are now more interconnected
      and interdependent than ever before. Africa is beleaguered by a range of endemic
      infectious and parasitic tropical diseases which, due to its diverse wildlife
      populations and indigenous livestock, can serve as a reservoir of high-impact or
      transboundary diseases and play a role in the emergence of disease, particularly
      at the wildlife, domestic animal and human interfaces. It is therefore essential
      to integrate animal and public health issues into the veterinary curriculum.
      Veterinary training in most parts of sub-Saharan Africa has focused on producing
      veterinarians to serve the livestock sector although socio-economic changes and
      privatisation of Veterinary Services have caused curriculum adjustments, as have
      globalisation and the increased risk of the spread of transboundary diseases. In
      South Africa, undergraduate veterinary training is more clinically oriented than
      in other regions. Animal and public health issues are covered in the curriculum,
      although their global relevance is not emphasised. The authors describe the
      undergraduate veterinary curriculum and summarise post-graduate programmes in
      South Africa. They also discuss a more comprehensive core-elective approach to
      the current curriculum and the need to adapt to new challenges facing the
      profession. Finally, they examine the potential use of innovative technology in
      undergraduate and post-graduate training and professional development, the
      importance of regional and international collaboration and the accreditation and
      recognition of veterinary training.

PMID- 20128485
TI  - Integrating the issues of global animal and public health into the veterinary
      education curriculum: a Latin American perspective.
AB  - This paper describes the development of a consensus profile for the Latin
      American veterinarian, and its adoption as the basis for curricular change by
      veterinary schools in the region. The process has been conducted by three Pan
      American organisations: the Pan American Association of Veterinary Science, the
      Pan American Federation of Veterinary Schools, and the Pan American Council of
      Veterinary Education, with strong backing bythe Food and Agriculture Organization
      of the United Nations. Recommendations for curricular harmonisation have been
      issued that will facilitate student and academic exchanges and, above all, will
      guarantee that the graduates from participating colleges have the knowledge,
      competencies and skills to adequately perform in the different fields of
      veterinary medicine, including those most relevant to global animal and public
      health.

PMID- 20128486
TI  - Integrating the issues of global and public health into the veterinary education
      curriculum: a European perspective.
AB  - Veterinary public health is an essential field in public health activities, based
      upon veterinary skills, knowledge and resources and which aims to protect and
      improve human health and welfare. This discipline has evolved through three
      stages, beginning with the fight against animal diseases, moving on to include
      meat inspection and control of zoonoses and now encompassing a much broader
      health sciences education, with the goal of guaranteeing a safe and wholesome
      food supply, protecting human wellbeing and conserving the environment. Within
      the veterinary medicine curriculum, veterinary public health has undergone a
      similar development. At first, it was mainly concerned with slaughterhouse-based
      courses but in time it included the teaching of such subjects as epidemiology,
      the control of communicable (zoonotic) diseases and emergency preparedness.
      Veterinary medical faculties in Europe have adjusted their curricula over the
      past few years to reflect these changes in the subject and to meet the need for
      specialisation. It could be said that veterinary public health education has
      literally moved from the local abattoir to the global community. In this paper,
      the authors briefly discuss examples of veterinary medicine curricula at
      different universities. The veterinary public health curriculum of the Faculty of
      Veterinary Medicine, Utrecht, is then discussed in detail, as an example of the
      European perspective on integrating global and public health issues into the
      veterinary curriculum.

PMID- 20128487
TI  - Innovation in veterinary medical education: the concept of 'One World, One
      Health' in the curriculum of the Faculty of Veterinary Medicine at the University
      of Calgary.
AB  - 'One World, One Health' is a foundation concept in veterinary medicine, much like
      comparative medicine. However, teachers of veterinary medicine often fail to
      identify it or speak of its importance within the veterinary curriculum. The
      resurgence of interest in the 'One World, One Health' concept aligns well with
      the underlying principles on which the University of Calgary Faculty of
      Veterinary Medicine (UCVM) has been newly founded. This concept is therefore a
      key component of the UCVM programme, and one that is well highlighted for those
      studying in the Doctor of Veterinary Medicine (DVM) course and graduate students.

PMID- 20128488
TI  - Innovations in veterinary education: the Charles Sturt University programme
      (Wagga Wagga, Australia).
AB  - Veterinary education must adapt to the changing demands that veterinary medicine
      is obligated to meet as it serves the needs of the ever-increasing global
      society. The world community needs the help of veterinary professionals to
      produce sufficient amounts of safe food, to control and eradicate the
      increasingly frequent transboundary transmission of disease, and to improve the
      health of both man and animals, at a global level as well as locally. In
      recognition of these mounting responsibilities, especially in the need for
      veterinarians in rural practice, one key venture in Australia has been the
      creation of the new veterinary school in Wagga Wagga. This paper describes the
      School's mission and, in particular, the nature of the new veterinary programme
      that has been created.

PMID- 20128489
TI  - Approaches to defining day-one competency: a framework for learning veterinary
      skills.
AB  - Competency at graduation, in a variety of physical and attitudinal skills, is an
      essential outcome measure for courses training veterinary surgeons. The approach
      adopted by the Royal Veterinary College, London, to identify and define the
      expected skill competencies required of our veterinary undergraduates by the time
      of graduation is described. In addition, we demonstrate how this skill set was
      built into a framework that was aligned with other student learning objectives.
      This two-year project resulted in the publication of a day-one skills handbook,
      which was introduced to the college staff and students in 2007.

PMID- 20128490
TI  - Defining, constructing and assessing learning outcomes.
AB  - Learning outcomes define the veterinary curriculum and inform students about what
      they must be able to demonstrate to succeed. Stakeholder consultation during
      their development ensures that programme learning outcomes equip graduates to
      contribute to the veterinary profession. Effective learning outcomes form a
      hierarchy linking the programme, its courses and tasks. Clear outcomes direct
      students towards higher quality learning by indicating the achievements intended,
      but leave scope for emergent learning outcomes. Defined technical competencies
      fit within this overarching framework, complementing higher order learning.
      Mapping is used to align learning outcomes horizontally and vertically so
      students are systematically guided towards entry-level competence and
      professional independence. Constructively aligned learning and assessment tasks
      ensure learners spend the focused time required to sequentially develop programme
      outcomes. Assessment by staff, peers and other stakeholders certifies achievement
      of intended outcomes. Effective assessment also empowers students to define and
      achieve their own learning outcomes, so they develop the habits of autonomous
      life-long learning. Evaluation of the quality and consistency of achieved
      outcomes informs ongoing programme improvement. If we are going to achieve the
      objectives of this set of papers, i.e. to improve public health education
      globally (Rev. sci. tech. Off. int. Epiz. 28 [2] 2009), then it is essential that
      they be well defined in the learning outcomes statement of all veterinary
      schools.

PMID- 20128491
TI  - Design and implementation of curriculum change.
AB  - In this paper, the authors propose adapting a four-stage model to design,
      implement and evaluate change in the curriculum for the degree of Doctor of
      Veterinary Medicine. For each stage, a relevant case study is presented to
      illustrate the application of the model. Factors facilitating change are
      described, as well as barriers to change. Strategies to overcome such barriers
      and the applicability of this model to other disciplines are also provided.

PMID- 20128492
TI  - Approaches to veterinary education--tracking versus a final year broad clinical
      experience. Part one: effects on career outcome.
AB  - This is the first of two papers that provide extensive data and analysis on the
      two major approaches to clinical veterinary education, which either provide
      students with experience of a broad range of species (often defined as
      omni/general clinical competence), or just a few species (sometimes just one),
      usually termed 'tracking'. Together the two papers provide a detailed analysis of
      these two approaches for the first time. The responsibilities of veterinary
      medicine and veterinary education are rapidly increasing throughoutthe globe. It
      is critical for all in veterinary education to reassess the approaches that have
      been used, and evaluate on a school-by-school basis which may best meet its
      expanding and ever-deepening responsibilities.

PMID- 20128493
TI  - Approaches to veterinary education--tracking versus a final year broad clinical
      experience. Part two: instilled values.
AB  - This is the second of two papers that the authors have written on this subject,
      and together they describe the results of the first major study of the outcomes
      of the two general approaches to the clinical training of veterinary students.
      One approach provides students with a broad experience with multiple species and
      the other provides them with an in-depth experience with just the species that
      they intend to work with in practice upon graduation (the latter is termed
      'tracking', i.e. students follow a course of study along a particular specialised
      'track'). This study obtained extensive feedback from the graduates of two
      schools, each of which was representative of one of the two approaches to
      clinical education. A total of 1,714 students took part in a survey in which they
      were asked to provide information about their career paths, their professional
      satisfaction, and their assessment of their training, especially in comparative
      veterinary medicine. They were also asked to say whether or not they would have
      preferred a different kind of training and who they would be most likely to hire
      as an associate: a tracking graduate or one who had received a broad-based
      education. The studies show that the several concerns that have been verbalised
      about tracking appear to be invalid. Upon graduation more than 90% of veterinary
      practitioners practice in quite a narrow area of veterinary medicine. We must,
      therefore, consider what benefits are gained from providing the typical very
      general preclinical education and offering students clinical training in animals
      with which they do not intend to practice upon graduation.

PMID- 20128494
TI  - Educational approaches aimed at preparing students for professional veterinary
      practice.
AB  - Changes in society and dissatisfaction with current educational practices have
      led to changes in undergraduate veterinary curricula. New approaches that are
      thought to better prepare students for future professional veterinary practice
      are being introduced. One such change is a transition from conventional teacher
      centred curricula to student-centred curricula. In student-centred curricula,
      students are actively involved in learning and teachers not only transmit
      knowledge but help students to obtain a deep understanding. Furthermore, learning
      within these curricula takes place in a multi-disciplinary context which is more
      relevant for the future of the profession. Another change is that more emphasis
      is put on training in academic skills, for instance, by establishing research
      internships. Finally, a new emphasis is being placed on training in more generic
      competencies, such as communication and business skills. These changes are
      assumed to better suit the profile of veterinary students today and in the future
      and to better prepare them for future veterinary practice.

PMID- 20128495
TI  - Principles of adult learning: the learning process.
AB  - Learning involves adding to the knowledge and skills of a student, and can be
      divided into a 'process' and an 'end product' or 'outcome'. In formal teaching,
      the focus is on pre-defined end products and it is hoped that the improvements in
      knowledge and skills are relatively permanent. However, this is not always the
      case, which is why it becomes important to examine the concept of 'transfer' more
      closely. 'Transfer' describes how well the knowledge and skills learned in one
      context can be applied by the student in another context. Several factors
      influence transfer. This paper describes the ways in which specific factors
      related to the student, the content of the course and the learning situation
      itself can influence the learning of new knowledge and skills. Furthermore, it
      examines how particular methods of learning can enable the knowledge and skills
      thus gained to be more easily applied in other circumstances.

PMID- 20128496
TI  - Distance education and its potential for international co-operative education.
AB  - This paper summarises some of the major trends in distance education in the first
      decade of the 21st Century, and explores the implications of these trends for
      international collaboration among institutions of veterinary medicine.

PMID- 20128497
TI  - Matching veterinary school accreditation to the global needs of the profession
      and global society.
AB  - In North America, the United Kingdom and Australasia, veterinary school
      accreditation is an integral part of the process of registering veterinarians to
      practise. In these regions, the relevant accrediting authority develops a set of
      standards which form the basis for individual schools to prepare a self
      evaluation report, in preparation for a site-visit team to spend a week
      validating the self assessment. Global trends in food production and animal
      movement increase the potential for spread of animal diseases and demands from
      trading partners to guarantee food quality standards. These and other trends in
      the practice of veterinary medicine require schools to continually review their
      curricula to accommodate workplace demands. Accreditation systems in the western
      world have been working together to improve collaboration and review standards
      but, to date, there has not been an international agency with responsibility for
      facilitating development of evolving and new systems. It is suggested that the
      World Organisation for Animal Health could consider whether it has a role in
      improving veterinary education by assisting in this area.

PMID- 20128498
TI  - Current approaches to veterinary school accreditation in Latin America.
AB  - This paper describes the development of veterinary school accreditation in Mexico
      and six South American countries. There is wide variation in the organisation of
      accreditation systems between countries, with different levels of involvement of
      national veterinary associations on the definition and/or operation of
      accreditation processes. There is also variation in the specificity of the
      standards used to evaluate veterinary education. In addition, the extent of
      implementation of accreditation mechanisms ranges from a country such as Mexico,
      where the first accreditation of a veterinary programme occurred more than ten
      years ago (there are now 15 accredited programmes), to countries such as Peru and
      Bolivia, which have not yet implemented an accreditation process for veterinary
      schools.

PMID- 20128499
TI  - Global health: setting the agenda for veterinary medical education to enable
      veterinarians to meet their responsibilities in the field.
AB  - We regard the set of papers in this issue (OIE Rev. sci. tech. Off. int. Epiz.,
      28 [2]) as a blueprint for an agenda to bridge the divides within the global
      scope of the veterinary profession, so that it will meet its responsibilities to
      the world as it develops in the coming decades. It defines the areas with which
      all veterinary students should be knowledgeable, provides emphasis on the need to
      expand the education of all veterinary students in terms of their global health
      responsibilities, and then provides insights into the educational approaches that
      can result in the inclusion of global health issues within the veterinary
      curriculum.

PMID- 20128500
TI  - Preventive effects of soy meal (+/- isoflavone) on spatial cognitive deficiency
      and body weight in an ovariectomized animal model of Parkinson's disease.
AB  - The aim of the present study was to investigate the preventive effect of 4 weeks
      soy meal (+/- isoflavone) on post-menopausal cognitive deficiency and body weight
      alteration in ovariectomized (OVX)-6-hydroxy dopamine (6-OHDA)-induced animal
      model of Parkinson's Disease (PD) which mimics status in menopause women. Female
      Wistar rats (250-300 g, 5-6 months old) were divided into 2 main groups. (1)
      Control; (2) OVX; included 5 subgroups that were pre-treated with 10 or 20 g soy
      with isoflavone in 30 g daily diet (10 and 20 groups, respectively), 10 or 20 g
      soy without isoflavone in 30 g daily diet (-10 and -20 groups, respectively) and
      0 g soy (sham treated group) during 4 weeks after OVX. To induce animal model
      ofPD in main second group (OVX rats) the substantia nigra pars compacta (SNpc)
      was lesioned by 6-hydroxydopamine (6-OHDA) (8 microg kg(-1) 4 microL(-1) normal
      saline contains 0.1% ascorbate). All animals were trained in Morris water maze
      for evaluating the spatial learning and memory. The results indicated that pre
      treatment of Parkinsonian rats with different doses of dietary soy meal (+/-
      isoflavone) improved the spatial learning and memory and prevents increasing the
      body weight after menopause significantly. Our data show that, long-duration
      dietary soy meal may have the potential neuroprotective effect against post
      menopausal cognitive deficiency induced by degeneration of nigrostriatal
      dopaminergic system and constant body weight during post-menopausal life cycle.

PMID- 20128501
TI  - An evaluation of eco-friendly naturally coloured cottons regarding seed cotton
      yield, yield components and major lint quality traits under conditions of East
      Mediterranean region of Turkey.
AB  - In the study carried out in 2002-2003 in the East Mediterranean region of Turkey
      (in Kahramanmaras Province), four different naturally coloured cotton (Gossypium
      hirsutum L.) (dark brown, light brown, cream and green) lines from Azerbaijan and
      two white linted cotton varieties (Maras-92 and Sayar-314 (G. hirsutum L.)) of
      the region were used as material. The aim of this study was to determine seed
      cotton yield and yield components and major lint quality traits of investigated
      coloured cotton lines comprising white linted local standard cotton varieties.
      Field trials were established in randomized block design with four blocks.
      According to two year's results, it was determined that naturally coloured
      cottons were found similar to both white linted standard cotton varieties for
      sympodia number and seed cotton yield. For boll number per plant, except green
      cotton line all coloured cotton lines were similar to standard varieties or even
      some of them were better than standards. For ginning outturn, dark brown, cream
      and green cotton lines were found statistically similar to standard Maras-92. But
      all naturally coloured cotton lines had lower seed cotton weight per boll and
      generally lower fiber quality than white linted standard varieties. For fiber
      length and fiber strength cream cotton line was the best coloured cotton. And for
      fiber fineness only green cotton line was better than both standards. It can be
      said that naturally coloured cotton lines need to be improved especially for
      fiber quality characters in the East Mediterranean region of Turkey.

PMID- 20128502
TI  - Brachial plexus blockade in elbow, arm or hand surgeries.
AB  - This study was performed to compare the transarterial (T) and paraarterial (P)
      approaches for brachial plexus block, in terms of success rate, onset time and
      duration of analgesia and complications. Hundred patients scheduled for elbow,
      arm or hand surgery at Tabriz Shohada hospital from October 2005 to December
      2006, randomly allocated into two groups (n=50 per group), based on the approach
      chosen to block the brachial plexus. For local anesthesia each patient received
      22.5 mL of 2% lidocaine with 17.5 mL distilled water (in total volume of 40 mL
      and total dose of 450 mg) and 1/200,000 epinephrine with a standard 23 gauge
      needle. All patients were sedated with 1 microg kg(-1) of fentanyl and 0.02-0.05
      mg kg(-1) of midazolam. There was no statistical difference between the groups in
      duration of analgesia but the onset of anesthesia was significantly quicker in
      paraarterial technique (3.5 vs. 13.4 min, p < 0.001). Success rate was 86% in
      group T and 98% in group P (p = 0.03). Two percent of patients in group P and 6%
      in group T had total failure of the block and 8% of the group T required
      supplementary drug. Paraarterial method for axillary block is preferable due to
      quicker onset of blockade and higher success rate.

PMID- 20128503
TI  - Daily sperm production of the domestic fowl (Gallus domesticus) as determined by
      quantitative testicular histology and homogenate methods.
AB  - The daily spermatozoa production was studied in 20 each of sexually matured
      barred Plymouth Rock and Nigerian indigenous breeds of domestic fowl using both
      the histometric and testicular homogenate methods. The exotic cocks were
      significantly (p < 0.01) heavier than the locals with the respective values of
      2.11 +/- 0.05 and 1.58 +/- 0.02 kg. The exotic also had larger (p < 0.01) gross
      testicular weight (21.58 +/- 1.46 vs. 12.56 +/- 0.91 g), paired testicular
      parenchymal weight (20.47 +/- 0.40 vs. 11.96 +/- 0.82 g) and paired tunica
      albuginea (1.11 +/- 0.18 vs. 0.60 +/- 0.11 g). The total length and the diameter
      of the seminiferous tubules were also significantly influenced (p < 0.01) by
      breed. The volume percent occupied by seminiferous tubules though higher in the
      exotic birds showed no statistical significance. Daily sperm production obtained
      from histometric method was highly influenced by breed with 2.41 +/- 1.17 x 10(9)
      and 0.76 +/- 0.71 x 10(9) for exotic and local cocks, respectively. The daily
      sperm productions calculated on the basis of homogenization-resistant spermatids
      were 1.85 +/- 0.22 for exotic and 0.73 +/- 0.11 for locals. Although, the
      difference in DSP values based on both methods was not statistically significant
      there was a 23.24 and 3.90% loss in exotic and local birds respectively with the
      use of homogenization method. On the whole, the exotic cocks were twice as
      efficient in sperm production as the local birds.

PMID- 20128504
TI  - Cross interaction of Pseudomonas putida and Glomus intraradices and its effect on
      wheat root colonization.
AB  - To study the cross interaction of microorganisms in plant growth promotion and
      the effect of auxin in this interaction, Pseudomonas putida and Glomus
      intraradices were co-inoculated on wheat. For this purpose, a mutant that
      produced less amount of auxin was derived from the bacterial strain by chemical
      mutagenesis with ethyl methane sulfonate. Next both the wild-type strain and the
      mutant strain were labeled with gusA for a better detection on the roots.
      Finally, the bacteria were inoculated on wheat as single inoculants or combined
      with arbuscular mycorrhizal fungi. Controls included non-bacteria/non-arbuscular
      mycorrhizal fungi and arbuscular mycorrhizal fungi alone. Plants co-inoculated
      with the wild-type bacterial strain and Glomus intraradices had the highest stem
      and their fresh and dry shoot weight was more than other treatments. Also, it was
      observed that the wild-type strain significantly improved the mycorrhizal
      colonization which implies the beneficial effect of auxin on mycorrhizal
      colonization. Furthermore, Glomus intraradices increased the population density
      of the wild-type strain in the endorhizosphere. In the microscopic studies of
      plant roots, bacterial colonies were observed as blues lines on the surface and
      inside the roots as well as on the seed surfaces.

PMID- 20128505
TI  - Depression prevalence and related factors in Iranian students.
AB  - This study designed to determine prevalence and related factors of depression in
      student of Arak, Iran. An analytical cross-sectional study was conducted on 304
      undergraduate medical and basic students in Arak Universities, Markazi Province,
      Iran from May 2008 to July 2008. GHQ-28 questionnaire has been used for data
      gathering and analyzed by t and Chi square tests. Mean of mental health in
      students was 26.18 +/- 11.02 and 52.3% of students scored above the threshold of
      the GHQ- 28, indicating psychiatric disorder. Female sex, uninteresting of major,
      an uncertain future and positive family history were the most important risk
      factors of depression. In results didn't observe any significant relationship
      between age, education major and year. The prevalence of depression was higher
      than as compared to all population and in female exceed to male students. But
      there wasn't any difference between medical and non medical students. So
      attention to financial and occupational future graduated and under graduated
      students is essential.

PMID- 20128506
TI  - Th-1/Th-2 cytokine pattern in human amoebic colitis.
AB  - Amoebiasis, caused by Entamoeba histolytica, is still considered a major health
      problem in developing countries. Since the immune response during human
      amoebiasis has not been clearly defined, we chose to evaluate cytokine production
      in patients suffering from amoebic colitis. A case-control association study was
      carried out on 62 subjects, including 31 patients with amoebic colitis and 31
      healthy controls (age, sex and geographic region-matched). Serum levels of IL-12,
      IFN-gamma, IL-13 and IL-5 were measured by solid-phase sandwich enzyme linked
      immunosorbant assay. Serum levels of IFN-gamma, IL-12, IL-13 and IL-5 were higher
      in the patients with amoebic colitis than in healthy controls, but were only
      statistically increased for IL-5 (p = 0.04) and IL-13 (p = 0.014). Stratification
      of patients according to gender revealed that IL-13 was significantly elevated in
      men as compared to levels measured in women (p = 0.04). These findings suggest
      that E. histolytica induce a mixed Th-1/Th-2 response with a polarization toward
      Th-2 during the early stage of amoebiasis, which may aide in developing a
      clinical illness.

PMID- 20128507
TI  - Skin disorders associated with bilateral lower extremity amputation.
AB  - We conducted this study to determine the types and frequency of skin problems
      among war related bilateral lower limb amputees. Three hundred and thirty five
      cases were examined for dermatologic problems in about 20 years (20 +/- 3.89)
      after bilateral lower extremity amputation. The subjects were injured during the
      Iraq-Iran war. Descriptive statistics were used. At least one skin problem was
      found in 189 (56.4%) of the amputees. Three hundred and nineteen skin problems
      were diagnosed in 189 amputees. The most common skin problems were contact
      dermatitis 39.5% (n=126), calluses 26.6% (n=85), folliculitis 14.42% (n=46) and
      ulcers 7.2% (n=23). The skin problems were more frequently seen in subjects with
      bilateral below the knee amputation. Skin problems were highly incident in our
      amputees. The substantial multidisciplinary rehabilitation team included a
      dermatologist, orthopedic surgeon, prosthetist and physical therapist is
      recommended to prevent and diagnose these problems on time.

PMID- 20128508
TI  - Nasal vestibular huge keratoacanthoma: an unusual site.
AB  - Keratoacanthoma (KA) is a rapidly growing, low-grade neoplasm of pilo-sebaceous
      and hair follicle units which most often appears on the sun-exposed skin of the
      middle aged and older persons with multiple or localized occurrence. This tumor
      is dome-shaped nodule with a central keratinous plug. The etiology of this tumor
      is not obvious. Exposure to excessive sunlight is the most frequently noted
      responsible factor in the etiology of KA. About 80% of the tumors occur on the
      face. The histological features of the KA are often very similar to those of a
      cutaneous squamous cell carcinoma; however, the tumor structure usually provides
      a basis for their difference. There are many unusual cases of keratoacanthoma
      reported regarding site, size or other specifications. In this study, we excised
      a mass of nasal vestibule, a site far away sun-exposure. To our knowledge, this
      is the first case of nasal vestibular keratoacanthoma. For a clinician and a
      pathologist it is important to consider a benign lesion like Keratoacanthoma (KA)
      in the differential diagnosis of ulcerated nasal lesions and pay attention to
      differ it from Squamous Cell Carcinoma (SCC) which has a different and aggressive
      management.

PMID- 20128509
TI  - Studies on heterosis in Abelmoschus esculentus (L.) Moench and A. callei (A.
      Chev) stevels cultivars during shorter day photoperiods in south eastern Nigeria.
AB  - Better parent heterosis was studied in direct and reciprocal crosses using 9
      early and late okra cultivars which belonged to the Early-early, Early-late, Late
      early and Late-late okra flowering types. The ANOVA for length of pod,
      circumference of pod, number of locules per pod, number of seeds per pod, Number
      of pods per plant, weight of 1000 seeds, density of seeds, weight of pods per
      plant, days to flower opening, plant height and circumference of stem at 10 cm
      above soil level, showed almost very highly significant differences-an indication
      that the cultivars are genetically diverse. Very highly significant, narrow and
      intermediate, heterosis was recorded for most of the direct and reciprocal
      crosses, showing that selections could be made from the hybrids to meet desired
      local okra qualities. A cross between an Early-late and Late-early parents, using
      early okra as the maternal parent, gave rise to a stable viable bridge hybrid
      which outperformed the better parent in many respects thereby overcoming the
      hitherto strong barrier to gene flow in interspecific hybridization studies
      involving the two okra types and also indicating the existence of maternal
      effects. Consequently with this development, the window has been opened for
      possible accelerated transfer of several desirable genes from late okra types to
      many promising but vulnerable early okra types. This could result to minimizing
      the further erosion of such early okra germplasm still in the custody of the
      local farmers.

PMID- 20128510
TI  - Effects of water deficit and spraying of dessicant on yield, yield components and
      water use efficiency of wheat genotypes.
AB  - To evaluate yield, yield components and water use efficiency of bread wheat in
      water stress conditions and spraying of dessicant, a field experiment was carried
      out in 2006-2007 and 2007-2008. Main plots were assigned to two levels of water
      stress treatments; D1: optimum irrigation and D2: cessation of watering from
      anthesis to maturity stages. Sub plots were assigned to eight bread wheat
      genotypes; and assimilates limitations with two levels: P1: no source limitation
      and P2: inhibition of current photosynthesis were in sub-sub plots. Grain yield,
      biological yield, harvest index, the number of grains per spike, thousand grain
      weight and water use efficiency were significantly influenced by irrigation
      treatments and source limitation. Grain Yield (GY) significantly decreased by 35
      and 68% under water deficiency and postanthesis photosynthetic inhibition,
      respectively; compared with control. Water use efficiency was higher for well
      watered compared with postanthesis drought stress conditions. WUEgrain decrease
      due to water deficit was attributed to grain yield reduction. Under water stress,
      current photosynthetic inhibition reduced grain yield by 62%, but under well
      watered condition; it significantly decreased grain yield by 71%, that indicate
      the source is limititing factor under different irrigation regimes. Considering
      that C-81-10, 9103 and 9116 genotypes showed the highest grain yield, potential
      for reserves and remobilizations of assimilates under different irrigation
      conditions; thus, these genotypes could be introduced as promising in breeding
      programs for arid and semi-arid regions.

PMID- 20128511
TI  - Safety margin in excision of basal cell carcinoma.
AB  - The aim of this study was to evaluate the intact margin after surgery regarding
      common method with consideration of 4 mm safe margin. Fifty patients with basal
      cell carcinoma operated in Tabriz Sina hospital, were chosen randomly and
      pathological report of these patients after surgery was evaluated with
      consideration of presence of intact margin. In pathologic report before operation
      of these patients, Basal cell carcinoma was certified. Also, brief data of these
      patients history was studied from present cases. Forty eight of 50 (96%) patients
      had intact margin after surgery and just in two patients (4%), lesion was excised
      insufficiently and they had involved margin. With brief study of patients'
      history, most of them had advanced ages and the most common site of tumor
      presentation was head and neck. The most of these patients had exposure with so
      much sun light that was accounted an important etiology. With comparison of
      mentioned statistical results with other reports from other countries, this rate
      is considered in acceptable range and surgical method is done properly in this
      hospital and consideration of 4 mm of tumoral margin is enough.

PMID- 20128512
TI  - In vitro callus induction and plant regeneration from Withania coagulans: a
      valuable medicinal plant.
AB  - Leaf and internode explants of Withania coagulans Dunal were used to evaluate the
      effect of growth regulators on the in vitro callus induction and plant
      regeneration. Two independent experiments were performed to establish callus and
      plant regeneration. In the first experiment, leaf segments were cultured on MS
      basal medium fortified with 2, 4-dichlorophenoxyacetic acid (2, 4-D, 2-4 mg L(
      1)) with combination of 6-benzyladenine (BA, 0.5-1 mg L(-1)) or kinetin (Kin, 0.5
      1 mg L(-1)). Callus initiation was observed best in all media after 14-16 days
      (100%). Highest callus growth in terms of dry weight (76 +/- 5.34 mg) was
      observed in MS medium fortified with 2 mg L(-1) 2, 4-D and 0.5 mg L(-1) Kin. In
      the second experiment, callusing also obtained from internode segments cultured
      on MS medium with the presence of 2, 4-D (2-4 mg L(-1)) in association with BA
      (0.25-0.5 mg L(-1)). Best callusing rates (42%) and dry weight (86 +/- 3.68 mg)
      occurred in the presence of 4 mg L(-1) 2, 4-D with combination of 0.25 mg L(-1)
      BA. Shoot induction was obtained just from callus induced from internode explants
      on MS medium containing BA (2 mg L(-1)) with IBA (0.5 mg L(-1)), but the yield of
      shoot regeneration was unsatisfactory (18-33%). Regenerated shoots were rooted
      best (100%) on half strength MS medium containing IBA (2 mg L(-1)) and produced
      23 roots with an average root length of 6.5 +/- 0.41 cm. Rooted plantlets
      transferred to soil and sand mixture (2:1) showed 75% survival when transferred
      to outdoor. The procedure reported here in vitro culture of W. coagulans for
      first time.

PMID- 20128513
TI  - Variations in thyroidal activity during estrous cycle and natural breeding season
      in Markhoz goat breeds.
AB  - The aim of this study was to determine the profile of changes in T3, T4 and TSH
      levels during breeding season and estrous cycle in Markhoz (Angora) Goats.
      Whereas the peaks of T3 were recorded in January, concentrations of T4 and TSH
      were highest in October. Variations in T3 and TSH concentrations among the
      different months of experiments period were not significant, although T4
      concentration was significantly higher during September, October and November in
      comparison to December and January. Weekly variations in serum T4 and TSH
      concentrations were directly correlated to the changes in photoperiod and
      temperature. Monthly variation in serum T3 and TSH did not have a significant
      (p>0.05) relationship with the changes in photoperiod and temperature, but there
      was a highly significant positive relationship between serum T4 and temperature.
      This study showed that T4 concentration was high in the early phase but decreased
      in the late phase of the breeding season, but T3 and TSH concentrations varied
      markedly from week to week. However, it appears that weekly rhythms are
      controlled by photoperiod and temperature because, changes in these factors
      resulted in different profiles of both T4 and TSH, but there was not any
      correlation between T3 and those factors.

PMID- 20128514
TI  - Monitoring population abundance of the sand lizard Acanthodactylus scutellatus
      and their ant prey in oil polluted soils at Kuwait's greater Al-Burgan oil field.
AB  - Desert ecosystems in Al-Burgan oil fields of Kuwait were contaminated by heavy
      metals and petroleum hydrocarbons due to oil spill generated by the Gulf War in
      1990. Studying sand lizard (Acanthodactylus scutellatus) population and their ant
      prey in the years 2002 and 2003 to detect the effects of oil pollution is now a
      focus of study. Polluted sites with apparently different degrees of pollution
      (namely tar mat, soot and clear sites) were compared with control sites outside
      this region. Total lizard numbers were recorded by using transect method. Number
      of ants was recorded by walking the transects and counting ants present. The
      results showed no difference in lizard population between the different study
      sites in 2002 and 2003 by applying the transect method. No difference in ant
      populations between the different study sites in 2002 and 2003. Although, the
      mean estimated lizard numbers were lower at the tar mat sites, the ant number in
      this location was greatest, meaning that food availability was highest at these
      sites. This suggests any reduction in the numbers of lizards is unrelated to low
      resource availability. The lizard numbers at the tar mat sites could be depressed
      by some property of the pollutants.

PMID- 20128515
TI  - Survey of ownership and use of mobile phones among medical science students in
      Yazd.
AB  - As the use of mobile phones is increasing every day, public concern about
      possible adverse health effects of exposure to radio frequency electromagnetic
      fields (rf-emf) is also growing. Despite the extensive use of mobile phones,
      little is known about the pattern of mobile phone ownership and its use by the
      general population and students. The aim of this study was to assess the pattern
      of ownership and use of mobile phones in medical science students and their views
      about any possible negative effects. The current cross-sectional study was
      conducted on 309 selected Medical Science students who were selected from Yazd
      Medical Sciences University using a self administrated questionnaire. The mean
      talking time and listening to music on the mobile phone was 28.3 +/- 50.5 and
      51.9 +/- 81.5 min day(-1), respectively. They also received or sent a mean of
      18.8 +/- 37 text messages. Participants reported that location wise, the use of
      cell phones at home was 87.2% followed by street (79.6%), classroom (37.6%),
      during driving (18.6%) and in the library (17.8%), respectively. Keeping at pace
      with changes in community and technology, including mobile phones and their
      effects on university environments, it seems that responsible departments or
      managers must predict their possible effects and establish new regulations,
      accordingly.

PMID- 20128516
TI  - Clinical and transperineal ultrasound findings in females with stress urinary
      incontinence versus normal controls.
AB  - Study was aimed at comparing clinical and transperineal ultrasound findings of
      females with stress urinary incontinence and normal controls. Between 2004 and
      2005, 40 women with stress urinary incontinence (mean age 47.5 years) diagnosed
      by history via ICIQ-SF (International consultation on Incontinence Questionnaire
      Short Form) and 40 healthy female volunteers without any incontinence or LUTS
      (mean age 42.1 years) underwent transperineal ultrasonography for determination
      of posterior urethrovesical (beta) angle, bladder neck funneling and
      hypermobility of urethra. These findings were compared between patients and
      controls with regard to clinical data. Beta angle wider than 130 degrees, bladder
      neck funneling and hypermobility of urethra with transperineal ultrasonography
      were more common among cases than controls. LR (Likelihood Ratio) for urinary
      incontinence of these parameters was 2.5, 2.1 and 2, respectively. Perineal
      ultrasonography is highly associated with clinical findings. Hypermobility of
      urethra had highest sensitivity for diagnose of stress urinary incontinence but
      the specificity of bladder neck funneling in perineal sonography was higher.

PMID- 20128517
TI  - Developing and implementing a survey to determine employer satisfaction with care
      provided to injured workers.
AB  - satisfaction surveys have become the primary means of evaluating perceptions of
      quality in the health care industry, including occupational health services. In
      occupational health, nurses need to know not only it injured workers are
      satisfied with their case, but also if injured workers' employers believe heath
      care provided to their workers was satisfactory. One problem is the lack of
      published surveys addressing issues relevant to occupational health services. the
      authors describe how a satisfaction was developed to understand employers'
      satisfaction with the case provided to injured workers. The theory of Self
      Administered Questionnaire Design, a previously used survey, and in put from
      multiple sources were used to develop the survey tool.

PMID- 20128518
TI  - Psychosocial factors affecting employees abilities to return to work.
AB  - This literature review explored the experiences of workers with on-the-job
      injuries, and the effect of psychosocial factors on their abilities to return to
      work. Four common themes were discovered frustration, depression, discrimination,
      and obstacles in understanding how the workers compensation system works and in
      obtaining care. The literature review suggested that interventions such as
      rehabilitation programs and psychosocial interventions help injured workers
      return to work. Nursing implications, including early, comprehensive, and fair
      interventions, are discussed. Intervening in this manner contributes to holistic
      nursing care of injured workers.

PMID- 20128519
TI  - When Is a "Generic" Medication not Really a Generic?
AB  - The distinction between pharmaceutical equivalent and pharmaceutical alternative
      drug products can lead to considerable confusion, especially with the
      proliferation of various branded, alternative, and generic medications that
      contain the same active ingredient. To illustrate this problem, four examples of
      medication products containing the active ingredients paroxetine, venlafaxine,
      bupropion, and valproate will be described. Understanding these differences is
      important for nurses providing patient care. Only generic drugs can be freely
      substituted for a brand-name product. Switching to a pharmaceutical alternative
      requires a change in prescription. Finally, the use, labeling, and cost of
      branded, alternative, and generic medications may be different.

PMID- 20128520
TI  - Drinking Games and College Students.
AB  - College students seek peer acceptance and opportunities for social interaction.
      For many, it may be the first time away from home, away from the supervision and
      watchful eyes of parents and other family members. Whether for fun, thrill,
      competition, or the need to socialize with others, approximately two thirds of
      U.S. college students participate in the risky binge drinking behavior called
      drinking games. Regardless of the game type, the goal of this behavior is to
      become intoxicated in a short period of time. Significant consequences and harm
      can result from this dangerous social behavior. This article, the first of two
      parts, will describe the problem; Part 2 will discuss the implications for
      community and mental health nurses.

PMID- 20128521
TI  - A Signature Wound of War.
AB  - Improvised explosive devices are the weapons of choice for the insurgent enemy in
      Iraq and Afghanistan. More soldiers are surviving these blast injuries due to
      improved torso protection yet are sustaining head and neck wounds in numbers that
      exceed those from previous wars. Although moderate and severe traumatic head
      injuries are easily identified and aggressively treated, mild traumatic brain
      injuries (m-TBIs), or concussions, had previously been deemed inconsequential and
      often overlooked. Recently, however, the U.S. Department of Defense and Veterans
      Health Administration have placed emphasis on identifying service members at risk
      for m-TBI because a select number continue to have disabling symptoms that can
      negatively affect quality of life. Research regarding the effects and treatment
      of blast injury are gaining momentum, but further work needs to be accomplished.
      This article provides a three-question screening tool that can be used to
      identify these at-risk veterans.

PMID- 20128522
TI  - Research with the doubly vulnerable population of individuals who abuse alcohol:
      an ethical dilemma.
AB  - Individuals who have maladaptive patterns of drinking alcohol fall into the
      category of vulnerable research participants for many reasons, not the least of
      which includes the stigma often placed on individuals who abuse alcohol.
      Vulnerable subgroups within the population of people who abuse alcohol include
      women; older adults; incarcerated, socioeconomically disadvantaged, and mentally
      ill individuals; as well as people from racial minorities. Thus, as research
      participants, individuals who abuse alcohol can be labeled a doubly vulnerable
      population. Belonging to more than one population simultaneously can lead to a
      compromised ability to protect one's own interests or greater susceptibility to
      harm related to participation in research studies. Arguments against including
      people who abuse alcohol as research participants will be presented, followed by
      the argument for including theses individuals, which is suggested as the more
      ethically sound of the two points of view.

PMID- 20128523
TI  - Psychotropic Medication-Induced Rabbit Syndrome.
AB  - Rabbit syndrome (RS) is an involuntary movement disorder characterized by rapid,
      fine movements of an individual's mouth, similar to the chewing movements of a
      rabbit, and has most frequently been associated with the use of antipsychotic
      medications. RS is often unrecognized or misdiagnosed as tardive dyskinesia or
      pseudoparkinsonism. Although rare, RS is easily treatable if recognized. It is
      essential that nurses are able to distinguish this syndrome from other movement
      disorders; however, a lack of information exists in the nursing literature about
      this syndrome. The aims of this article are to describe the clinical symptoms of
      RS, its prevalence and etiology, and recommended treatment. Clinical and
      educational implications regarding RS are also provided.

PMID- 20128524
TI  - The importance of getting back to nature for people with dementia.
AB  - As people age, the ability to interact with the outdoors may lessen. Frailty and
      mobility problems create barriers to engaging in outdoor activities or even
      experiencing the outdoors. The barriers are greater for people with dementia. As
      the disease worsens to the point of institutionalization, access to the outdoors
      may be completely barred and opportunities relinquished to the determination of
      facility personnel. This article will review current literature and some older
      seminal works on nature and nature-based stimuli for people with dementia,
      especially those living in nursing homes.

PMID- 20128525
TI  - Prevention and clinical outcomes in older inpatients with suspected venous
      thromboembolism.
AB  - Venous thromboembolism (VTE) is one of the most common preventable disorders
      among hospital inpatients. Advancing age is a major risk factor for VTE. The
      purpose of this study was to describe and compare prevention practices and
      clinical outcomes in older (age 65 and older) versus younger (ages 18 to 64)
      hospitalized patients at risk for or diagnosed with VTE. Medical charts of 210
      older and 450 younger inpatients undergoing diagnostic tests to rule out VTE were
      reviewed at an academic medical center. Acute VTE was diagnosed in 17.1% of older
      and 22.7% of younger inpatients. Pharmacological prophylaxis was used in 70% of
      eligible older and 57% of eligible younger inpatients. Nearly one quarter of
      eligible older inpatients did not receive any VTE prevention measures. The 3
      month mortality was higher in older inpatients (13.9%) compared with younger
      inpatients (9.8%) with VTE, despite the lower rate of VTE in older inpatients.
      Prevention measures for VTE were underused in both older and younger inpatients.

PMID- 20128526
TI  - Use of pain-behavioral assessment tools in the nursing home: expert consensus
      recommendations for practice.
AB  - Many tools are available for the assessment of pain in nonverbal older adults;
      however, guidelines are needed to help clinicians select the proper instrument
      for use in the nursing home setting. This article describes a project to identify
      clinically useful pain-behavioral assessment tools that have undergone sufficient
      psychometric testing. Phase 1 of the project included a comprehensive review and
      critique of currently available tools. In Phase 2 the National Nursing Home Pain
      Collaborative developed criteria to evaluate an updated list of tools and then
      rated 14 tools using these criteria. As a result, two tools were recommended as
      most representative of current state of the science, most clinically relevant,
      and practically applicable to integrate into everyday practice and support
      adherence to regulatory guidelines. Such recommendations for selection of best
      available pain assessment tools are a cornerstone for clinicians in regard to
      managing pain of nursing home residents who, due to dementia, are unable to self
      report pain.

PMID- 20128527
TI  - Under pressure: nursing liability and skin breakdown in older patients.
AB  - The geriatric patient presents many challenges to the professional nurse. As the
      body ages, its protective outer covering and largest organ, the skin, also
      changes. With an older adult's decreased mobility and amount of subcutaneous fat
      comes lessened protection from surfaces or bony prominences. As such, older
      adults' skin becomes weaker and more prone to breakdown and presents myriad
      challenges to the patient's well-being. One of the most hazardous challenges are
      pressure ulcers. Educating geriatric nurses in how to identify those at risk,
      accurately identify and categorize pressure ulcers, and limit or, ideally,
      eliminate their professional liability is essential to the effective care and
      treatment of this at-risk population.

PMID- 20128528
TI  - Fall risk in community-dwelling elderly cancer survivors: a predictive model for
      gerontological nurses.
AB  - The aim of this predictive study was to test a structural model to establish
      predictors of fall risk in elderly cancer survivors. An aging and nursing model
      of care was synthesized and used to examine the Minimum Data Set for 6,912 low
      income older adult participants in a community setting in the midwestern United
      States. Data analysis established relationships among fall risk and age,
      race/ethnicity, history of a previous fall, depression, pain, activities of daily
      living, instrumental activities of daily living, incontinence, vision, and
      cognitive status. Factors leading to fall risk can direct nursing activities that
      have the potential to prevent falls, thus improving older adults' quality of
      life.

PMID- 20128529
TI  - Intraoperative complications of LASIK flaps using the IntraLase femtosecond laser
      in 3009 cases.
AB  - PURPOSE: To report the incidence and management of intraoperative complications
      while using the IntraLase FS femtosecond laser (Abbott Medical Optics) for flap
      creation during LASIK. METHODS: A prospective log of intraoperative flap creation
      complications using the femtosecond laser was maintained over 3009 consecutive
      LASIK surgeries from August 2002 through July 2009. RESULTS: Eleven (0.37%)
      intraoperative complications occurred. Eight suction breaks occurred, seven of
      which were treated with reapplication of the laser, the other by completing the
      side-cut with surgical dissection. One case of incomplete flap creation was
      treated with surgical dissection. Two cases of adherent flap were treated with
      reapplication of laser energy and surgical dissection. All surgeries were
      completed successfully during the same operative session. CONCLUSIONS:
      Intraoperative complications during flap creation are minor, infrequent, and can
      be managed effectively within the same surgical session.

PMID- 20128530
TI  - Distribution of angle kappa measurements with Orbscan II in a population-based
      survey.
AB  - PURPOSE: To determine the mean angle kappa and its determinants in the population
      of Tehran, Iran. METHODS: In a cross-sectional survey with random cluster
      sampling, a total of 442 participants aged >14 years were selected from 4
      municipality districts of Tehran for Orbscan acquisitions. Exclusion criteria
      were history of eye surgery for refractive errors, cataract or glaucoma, and use
      of topical medication or any type of contact lens at the time of the study. Mean
      angle kappa in different age and gender groups and its association with other
      factors was assessed. Considering the high correlation between the right and left
      eyes, only results of the right eyes are presented. RESULTS: After applying
      exclusion criteria, 800 eyes (399 right eyes and 401 left eyes) were examined.
      Mean participant age was 40.6+/-16.8 years (range: 14 to 81 years), and 38.8% of
      eyes were from men. Mean angle kappa was 5.46+/-1.33 degrees  in total; 5.41+/
      1.32 degrees  in men and 5.49+/-1.34 degrees  in women (P=.558). It decreased
      significantly with age; 0.015 degrees /year (P<.001). In individuals with myopia,
      emmetropia, and hypermetropia, the mean value was 5.13+/-1.50 degrees , 5.72+/
      1.10 degrees , and 5.52+/-1.19 degrees , respectively (P=.025); the post-hoc test
      indicated this was due to the difference between emmetropes and myopes.
      CONCLUSIONS: According to our results, angle kappa reduces with age, and the
      inter-gender difference is not significant. Largest angle kappas were seen among
      individuals with emmetropia. Angle kappas were larger in the hypermetropic
      population compared to the myopic population.

PMID- 20128531
TI  - Optical and topographic changes in keratoconus after implantation of Ferrara
      intracorneal ring segments.
AB  - PURPOSE: To assess the morphological, optical, and visual properties of the
      cornea before and after implantation of Ferrara intracorneal ring segments (ICRS)
      and compare them to normal values. METHODS: Thirty-seven keratoconic eyes were
      implanted with Ferrara ICRS and compared pre- and postoperatively with 38 non
      keratoconic (normal) eyes. Examinations were performed using the NIDEK Optical
      Path Difference (OPD)-Scan II and analyzed using OPD-Station software.
      Keratometric data were assessed, in addition to OPD, Zernike coefficients, point
      spread function (PSF), and modulation transfer function (MTF). RESULTS:
      Considering correlations, the central 3 mm cornea was found responsible for the
      low quality vision in keratoconus (P<.01). After implantation of Ferrara ICRS,
      all keratometric parameters improved significantly. Optical path difference also
      improved. Except for tilt and other lower order Zernike coefficients, higher
      order aberrations, PSF, and MTF did not change. The effect of flattening is
      greater at the central 3 mm, but the para-central changes are responsible for the
      residual defects (ie, incomplete improvements of high optical and visual
      functions). CONCLUSIONS: Ferrara ICRS improve topographic and visual results in
      keratoconic eyes.

PMID- 20128532
TI  - Mechanism of action of the tetraflex accommodative intraocular lens.
AB  - PURPOSE: To investigate the mechanism of action of the Tetraflex (Lenstec Kellen
      KH-3500) accommodative intraocular lens (IOL). METHODS: Thirteen eyes of eight
      patients implanted with the Tetraflex accommodating IOL for at least 2 years
      underwent assessment of their objective amplitude-of-accommodation by
      autorefraction, anterior chamber depth and pupil size with optical coherence
      tomography, and IOL flexure with aberrometry, each viewing a target at 0.0 to
      4.00 diopters of accommodative demand. RESULTS: Pupil size decreased by 0.62 +/-
      0.41 mm on increasing accommodative demand, but the Tetraflex IOL was relatively
      fixed in position within the eye. The ocular aberrations of the eye changed with
      increased accommodative demand, but not in a consistent manner among individuals.
      Those aberrations that appeared to be most affected were defocus, vertical
      primary and secondary astigmatism, vertical coma, horizontal and vertical primary
      and secondary trefoil, and spherical aberration. CONCLUSIONS: Some of the
      reported near vision benefits of the Tetraflex accommodating IOL appear to be due
      to changes in the optical aberrations because of the flexure of the IOL on
      accommodative effort rather than forward movement within the capsular bag.

PMID- 20128533
TI  - Corneal collagen cross-linking with riboflavin and UVA irradiation in pellucid
      marginal degeneration.
AB  - PURPOSE: To report the results of corneal collagen cross-linking (CXL) with
      riboflavin and ultraviolet A irradiation in a patient affected by pellucid
      marginal degeneration (PMD). METHODS: A 43-year-old man with bilateral PMD
      underwent CXL in the left eye. The treatment was performed in standard fashion
      with the exception of slightly inferior decentration of the 9 mm-diameter
      irradiated area preserving an untreated surface area 1 mm from the limbus.
      RESULTS: Epithelial regrowth was complete after 4 days' use of a bandage soft
      contact lens. No side effects or damage to the limbal region were observed during
      re-epithelialization or during follow-up. Corrected distance visual acuity
      improved from 20/200 to 20/63 at 3 months and was stable through the 12-month
      interval. Keratometric astigmatism showed a 1.40-diopter (D) reduction and the
      power of ectasia apex decreased from 82.00 D to 78.00 D. CONCLUSIONS: Corneal
      collagen CXL was a safe tool in the management of PMD, improving some parameters
      in advanced stages of the disease.

PMID- 20128534
TI  - Corneal ablation depth readout of the MEL 80 excimer laser compared to Artemis
      three-dimensional very high-frequency digital ultrasound stromal measurements.
AB  - PURPOSE: To evaluate the accuracy of the ablation depth readout for the MEL 80
      excimer laser (Carl Zeiss Meditec). METHODS: Artemis 1 very high-frequency
      digital ultrasound measurements were obtained before and at least 3 months after
      LASIK in 121 eyes (65 patients). The Artemis-measured ablation depth was
      calculated as the maximum difference in stromal thickness before and after
      treatment. Laser in situ keratomileusis was performed using the MEL 80 excimer
      laser and the Hansatome microkeratome (Bausch & Lomb). The Aberration Smart
      Ablation profile was used in 56 eyes and the Tissue Saving Ablation profile was
      used in 65 eyes. All ablations were centered on the corneal vertex. Comparative
      statistics and linear regression analysis were performed between the laser
      readout ablation depth and Artemis-measured ablation depth. RESULTS: The mean
      maximum myopic meridian was -6.66+/-2.40 diopters (D) (range: -1.50 to -10.00 D)
      for Aberration Smart Ablation-treated eyes and -6.50+/-2.56 D (range: -1.34 to 
      11.50 D) for Tissue Saving Ablation-treated eyes. The MEL 80 readout was found to
      overestimate the Artemis-measured ablation depth by 20+/-12 MUm for Aberration
      Smart Ablation and by 21+/-12 MUm for Tissue Saving Ablation profiles.
      CONCLUSIONS: The accuracy of ablation depth measurement was improved by using the
      Artemis stromal thickness profile measurements before and after surgery to
      exclude epithelial changes. The MEL 80 readout was found to overestimate the
      achieved ablation depth. The linear regression equations could be used by MEL 80
      users to adjust the ablation depth for predicted residual stromal thickness
      calculations without increasing the risk of ectasia due to excessive keratectomy
      depth as long as a suitable flap thickness bias is included.

PMID- 20128535
TI  - Outcomes and patient satisfaction after presbyopic bilateral lens exchange with
      the ResTOR IOL in emmetropic patients.
AB  - PURPOSE: To assess efficacy, safety, predictability, stability, and patient
      satisfaction after presbyopic lens exchange in emmetropic patients. METHODS: A
      prospective, nonrandomized, masked, observational case series (self-controlled)
      of 46 emmetropic eyes of 23 consecutive patients (age range: 50 to 60 years)
      after presbyopic lens exchange with bilateral AcrySof ReSTOR Natural (SN60D3)
      intraocular lens (IOL) (Alcon Laboratories Inc) implantation were evaluated. Mean
      spherical equivalent refraction (SE) was -0.04+/-0.14 diopters (D) (range: +0.25
      to -0.25 D). Monocular and binocular uncorrected distance visual acuity (UDVA),
      corrected distance visual acuity (CDVA), uncorrected near visual acuity (UNVA),
      distance-corrected near visual acuity (DCNVA), and patient satisfaction were
      recorded preoperatively and 6 months after surgery. RESULTS: At 6 months
      postoperative, efficacy index at distance was 1.00. No eye lost >=2 lines of
      CDVA, 5 eyes lost 1 line, 24 eyes did not change after surgery, 14 eyes gained 1
      line, and 3 eyes gained 2 lines of visual acuity. Safety index at distance was
      1.03. All eyes had a manifest SE within +/-0.50 D of emmetropia. Mean
      postoperative SE was +0.14+/-0.22 D (range: -0.25 to +0.37 D). No eye lost >2
      lines of DCNVA, 1 eye lost 2 lines, 3 eyes lost 1 line, 34 eyes did not change
      after surgery, and 8 eyes gained 1 line of visual acuity. Uncorrected near visual
      acuity was 0.95+/-0.07. Safety and efficacy indexes at near were 1.01 and 1.03,
      respectively. A patient satisfaction questionnaire showed that patients had a
      high level of satisfaction after presbyopic lens exchange surgery. CONCLUSIONS:
      Presbyopic lens exchange with implantation of the ReSTOR multifocal IOL in
      emmetropic eyes is an effective and safe procedure for presbyopia correction.

PMID- 20128537
TI  - What's the rush? Internal validity is not a trivial pursuit.

PMID- 20128538
TI  - Benefits and challenges of electronic surveillance in nursing home research.
AB  - Cognitive impairment and frailty associated with dementia renders residents of
      long-term care (LTC) facilities particularly vulnerable to physical and emotional
      harm. Resident-to-resident violence affects not only the target of the
      aggression, but also the aggressor, as well as the formal and informal caregivers
      who must intervene. To date, little research has been conducted on resident-to
      resident violence despite preliminary but emerging evidence that it is a common
      (and likely growing) problem in LTC settings. Exploration of this phenomenon
      presents multiple pragmatic and ethical challenges. This article presents a
      rationale for implementing newer technological methods to collect data in
      investigations of resident-to-resident violence associated with dementia. The
      advantages and disadvantages of electronic surveillance in LTC research and the
      ethical principles involved are discussed, and an argument is developed for using
      electronic surveillance in both the shared, as well as private, spaces of the
      facility.

PMID- 20128539
TI  - An innovative approach to recruiting homebound older adults.
AB  - Recruiting older adults to participate in intervention research is essential for
      advancing the science in this field. Developing a relevant recruitment plan
      responsive to the unique needs of the population before beginning a project is
      critical to the success of a research study. This article describes our
      experiences in the process of recruiting homebound older adults to test a
      community-based health empowerment intervention. In our study, the trust and
      partnership that existed between the research team and Community Action Agency
      facilitated the role of the home-delivered meal drivers as a trusted and untapped
      resource for study recruitment. Researchers can benefit from thinking creatively
      and developing meaningful partnerships when conducting research with older
      adults.

PMID- 20128540
TI  - Pilot study of a brief behavioral sleep intervention for caregivers of
      individuals with dementia.
AB  - Informal caregivers of individuals with dementia experience higher rates of poor
      sleep quality and depression than the general population. Short-term behavioral
      interventions have been shown to improve sleep quality in other caregiver
      populations. The purposes of this study were to determine the feasibility of the
      CAregiver Sleep Intervention (CASI) in a small sample of caregivers of both
      community-dwelling and institutionalized individuals with dementia. The
      caregivers were given CASI, a 5-week behavioral sleep intervention combining
      relaxation, stimulus control, and sleep hygiene with personal goal setting,
      delivered at the caregiver's convenience. Caregivers reported no increased burden
      with CASI. The intervention was well received, and sleep quality and depression
      trended toward improvement. CASI appears to be feasible and beneficial in this
      small sample and warrants further study in caregivers of individuals with
      dementia.

PMID- 20128541
TI  - Women's and men's exercise adherence after a cardiac event.
AB  - The purpose of this secondary analysis was to determine whether age affects
      women's and men's exercise adherence after a cardiac event. In a convenience
      sample of 248 adults ages 38 to 86 who had a cardiac event, exercise adherence
      (three exercise sessions per week) was compared between men and women in three
      age groups (younger than 60, 61 to 70, and older than 70). Exercise patterns were
      recorded by heart rate monitors worn during exercise. No differences were found
      in adherence between the age groups for women; older men were nonadherent sooner
      than younger men when controlling for fitness level, pain, comorbidity, self
      efficacy, depressed mood, and social support. Exercise adherence after a cardiac
      event was higher for younger men compared with older men. For all age groups,
      less than 37% of the total sample adhered to a three-times-per-week exercise
      regimen after 1 year, suggesting that interventions to maintain exercise
      adherence are needed.

PMID- 20128542
TI  - The cumulative influence of conflict on nursing home staff.
AB  - Nursing staff burnout is a significant challenge in the delivery of nursing home
      care. Using a representative sample of nursing staff working within the nursing
      home setting, our analysis addressed the influence of conflict with residents'
      families on the burnout experience of staff. Through the use of computer
      simulation modeling we were able to assess the cumulative effects of conflict
      between staff and families. Findings indicated that conflict with the residents'
      families increased both burnout and dissatisfaction among nursing staff. The
      burnout experience of nursing staff peaked with initial episodes of conflict,
      then leveled off as simulated conflict with family members continued. Because
      previous research has indicated that burnout tends to peak early in nurses'
      career cycle, the finding that initial episodes of conflict have a strong
      influence on nursing staff burnout highlights the importance of interpersonal
      conflict within nursing homes in both individual and institutional outcomes.

PMID- 20128543
TI  - Health literacy issues among women with visual impairments.
AB  - The purpose of this secondary analysis using qualitative description was to
      explore health literacy using the health care experiences of women with permanent
      visual impairments (VIs). Interviews were analyzed from a sample of 15 community
      dwelling women ages 44 to 79 with permanent VIs who had participated in a larger
      grounded theory study. The 15 women were interviewed twice; the audio-recorded
      interviews were then transcribed verbatim and analyzed using qualitative content
      analysis. Using the Institute of Medicine's definition of health literacy, the
      women's experiences were categorized into their ability to obtain, process, and
      understand health information. Their perceptions of the factors that influenced
      their health literacy were also explored. The women voiced that barriers to their
      ability to gain information in a format amenable to their processing skills,
      combined with barriers arising from health care providers' attitudes, undermined
      their ability to build health literacy capacity.

PMID- 20128544
TI  - Technology for long-term care.
AB  - Severe staff shortages in long-term care (LTC) make it difficult to meet the
      demands of the growing aging population. Further, technology-savvy Baby Boomers
      are expected to reshape the current institutional environments toward gaining
      more freedom and control in their care and lives. Voices from business, academia,
      research, advocacy organizations, and government bodies suggest that innovative
      technological approaches are the linchpin that may prepare society to cope with
      these projected demands. In this article, we review the current state of aging
      related technology, identify potential areas for efficacy testing on improving
      the quality of life of LTC residents in future research, and discuss barriers to
      implementation of LTC technology. Finally, we present a vision of future
      technology use that could transform current care practices.

PMID- 20128545
TI  - Treatment of a manifest strabismus with amblyopia.

PMID- 20128546
TI  - Glaucoma associated with phacomatosis pigmentovascularis.

PMID- 20128547
TI  - Is initial overcorrection after surgical correction for intermittent exotropia
      necessary?

PMID- 20128548
TI  - Exotropic drift and ocular alignment after surgical correction for intermittent
      exotropia.
AB  - PURPOSE: To evaluate changes in the angle of deviation over time and compare the
      motor success rate with different initial postoperative deviation in patients
      undergoing surgical correction for intermittent exotropia. METHODS: Forty-eight
      patients aged between 1 and 10 years who underwent bilateral lateral rectus
      recession for intermittent exotropia were retrospectively evaluated. Preoperative
      and postoperative ocular deviations at 1 week, 1 month, and 6 months were
      analyzed. Full surgical correction was attempted in all patients. Motor success
      was defined as ocular deviation within 10 prism diopters of orthophoria at 6
      months postoperatively. RESULTS: The follow-up period ranged from 6 months to 3
      years. Although most patients had exotropic drift, this drift was greater in
      patients with initial esotropia (86.7%) and orthophoria (70.0%) compared to
      patients with exotropia (26.1%). Motor success was achieved in 29 (60.4%)
      patients. There was no statistical difference between ocular alignment at 1 week
      postoperatively and final motor success (P = .782). There was good correlation
      between ocular alignment at 1 week and 6 months postoperatively (rho = 0.585, P <
      .001). Age and preoperative deviation were not found to be associated with motor
      success. CONCLUSIONS: The success rate appears to be unaffected by initial ocular
      alignment, suggesting that deliberate initial overcorrection may be unnecessary.
      Future studies are warranted to evaluate the long-term stability of this
      alignment.

PMID- 20128549
TI  - Macular abnormality observed by OCT in children with amblyopia failing to achieve
      normal visual acuity after long-term treatment.
AB  - PURPOSE: To investigate why some children with amblyopia fail to achieve normal
      visual acuity. METHODS: Optical coherence tomography (OCT) was perform to observe
      the morphology of the macular tissue of children with various types of amblyopia
      who failed to achieve normal visual acuity (< or = 20/25). Average thickness of
      the retinal nerve fiber layer (RNFL) of the foveola and fovea (1-mm diameter
      range) was then assessed by macular retinal tomography map measurement. The data
      obtained were compared with those considered normal to detect any abnormality.
      RESULTS: Fifteen patients (24 eyes) were examined. Images showed abnormality with
      thickness RNFL in the macular area in which

PMID- 20128550
TI  - Refractive errors and strabismus in children with laurence-moon-biedl syndrome.
AB  - PURPOSE: To describe the ocular and refractive findings in patients with Laurence
      Moon-Biedl syndrome. METHODS: Seventeen patients with Laurence-Moon-Biedl
      syndrome were evaluated retrospectively. All children underwent complete
      ophthalmologic examination. RESULTS: Of the patients evaluated, 88.2% had an
      ocular or refractive finding, 58.8% had myopia (degenerative in three cases),
      52.9% had astigmatism, 11.7% had an-isometropia, 17.6% had strabismus, 11.7% had
      retinitis pigmentosa, 5.9% had keratoconus, 5.9% had optic atrophy, and 5.9% had
      nystagmus. CONCLUSION: Early and regular ophthalmologic assessment is required to
      prevent visual loss as a result of amblyogenic factors in children with Laurence
      Moon-Biedl syndrome.

PMID- 20128551
TI  - High measured intraocular pressure in children with recessive congenital
      hereditary endothelial dystrophy.
AB  - PURPOSE: To report the phenomenon of high measured intraocular pressure in
      recessive congenital hereditary endothelial dystrophy. METHODS: A case series was
      retrospectively reviewed. RESULTS: Five infants with significant congenital
      corneal haze had increased measured intraocular pressure that remained high
      despite drug treatment and surgery to decrease intraocular pressure. The clinical
      diagnosis of recessive congenital hereditary endothelial dystrophy without
      glaucoma was made based on the absence of buphthalmos, a distinct pattern of
      mosaic corneal haze with significant corneal thickness, and absence of cupping in
      healthy-appearing optic nerve heads. CONCLUSION: Intraocular pressure can be
      falsely elevated in some children with recessive congenital hereditary
      endothelial dystrophy, leading to confusion with congenital glaucoma.

PMID- 20128552
TI  - Clinical and histologic ocular findings in pompe disease.
AB  - PURPOSE: Limited information is available on the ocular findings in patients with
      Pompe disease. METHOD: This study summarizes this information with a systematic
      literature review; reports the ocular histologic findings seen in a deceased
      infant with Pompe disease who was receiving enzyme replacement therapy and in a
      deceased adult with late-onset Pompe disease; and notes the new observation of
      ptosis in children with infantile-onset Pompe disease who are receiving enzyme
      replacement therapy. RESULTS: Six articles were found on the ultrastructural
      histopathologic eye findings in Pompe disease. Previously reported clinical
      ocular findings included strabismus and ptosis. Glycogen accumulation and
      vacuolar myopathy have been seen histologically. CONCLUSION: Based on these
      clinical and histologic reports, patients with Pompe disease may have an
      increased incidence of ocular abnormalities, such as ptosis and strabismus, and
      therefore should undergo ophthalmologic examination.

PMID- 20128553
TI  - Novel technique for Nd:YAG posterior capsulotomy in pediatric patients.
AB  - A 7-year-old girl had posterior capsule opacification 2 years after cataract
      extraction without posterior capsulotomy. This report describes a novel technique
      for Nd:YAG posterior capsulotomy in pediatric patients for providers who do not
      have access to an overhead-mounted Nd:YAG laser.

PMID- 20128554
TI  - Infectious keratitis in a newborn with goldenhar syndrome.
AB  - Goldenhar syndrome is a rare, presumably inherited condition that has a
      multifactorial etiopathology that results in disturbances of blastogenesis. The
      syndrome is characterized by the presence of dermal epibulbar tumors,
      periauricular appendices, malformed ears, and vertebral anomalies, with
      occasional occurrence of cardiac, visceral, or central nervous system anomalies.
      This report describes a case of Goldenhar syndrome in a newborn who presented
      with all of the classic signs of Goldenhar syndrome associated with the rare
      occurrence of infectious keratitis and hydrocephalus.

PMID- 20128555
TI  - Orbital recurrence of B-progenitor acute lymphoblastic leukemia in a child.
AB  - Orbital mass is an exceedingly rare presentation of acute lymphoblastic leukemia.
      This report describes a 12-year-old boy with recurrent orbital pre-B-cell acute
      lymphoblastic leukemia and reviews the literature on the incidence, presentation,
      prognosis, and management of orbital tumors in acute lymphoblastic leukemia.
      Early diagnosis and treatment of orbital acute lymphoblastic leukemia with a
      multidisciplinary approach is essential to minimize or prevent deterioration of
      vision and optimize clinical outcomes.

PMID- 20128556
TI  - Congenital horizontal tarsal kink with microphthalmos corrected by intermarginal
      suture tarsorrhaphy.
AB  - Congenital horizontal tarsal kink is extremely rare. Only one case of associated
      microphthalmos has been reported. Various surgical techniques have been described
      with successful results. Few reported cases have been managed with intermarginal
      suture tarsorrhaphy. The current case is probably the third patient with severe
      tarsal kink to be managed with this simple technique.

PMID- 20128557
TI  - Takayasu's disease and secondary ocular ischemic syndrome.
AB  - Takayasu's, or "pulseless," disease is a rare, idiopathic, chronic granulomatous
      vasculitis that affects large arterial blood vessels. Ocular manifestations occur
      as a consequence of obliteration of the carotid artery, and ocular ischemia may
      develop. A 14-year-old girl with progressive visual loss and ocular ischemic
      syndrome secondary to Takayasu's disease is described.

PMID- 20128558
TI  - Iris transillumination defects associated with pallister-killian syndrome.
AB  - This report describes a new finding of iris transillumination defects in
      Pallister-Killian syndrome, a rare multi-system disorder resulting from mosaic
      tetrasomy of the short arm of chromosome 12.

PMID- 20128559
TI  - Improving the sun safety of bicycle helmets.

PMID- 20128560
TI  - Downbeat nystagmus as the sole sign of Chiari malformation in goldenhar syndrome.

PMID- 20128561
TI  - Nasoethmoidal cephalocele with bilateral orbital extension presenting as
      bilateral lower eyelid mass.

PMID- 20128562
TI  - Optical coherence tomography: a new tool for intraoperative decision making.
AB  - Optical coherence tomography (OCT) has traditionally been used in the outpatient
      environment as an important diagnostic tool for retinal clinical decision making.
      Recent advances in OCT technology have made intraoperative use of OCT feasible.

PMID- 20128563
TI  - Intraoperative OCT of a full-thickness macular hole before and after internal
      limiting membrane peeling.
AB  - A child with a traumatic full-thickness macular hole was imaged perioperatively
      using spectral-domain optical coherence tomography (SD-OCT). Intraoperative
      imaging using a portable SD-OCT device equipped with a handheld probe
      demonstrated the full-thickness macular hole to be nearly completely closed
      following vitrectomy and internal limiting membrane peeling. Air was used as a
      tamponade agent and prone positioning was used postoperatively for 2 days. SD-OCT
      imaging confirmed closure of the full-thickness macular hole 5 days and 1 month
      postoperatively.

PMID- 20128564
TI  - Transpupillary thermotherapy of subfoveal choroidal neovascularization secondary
      to pathologic myopia.
AB  - BACKGROUND AND OBJECTIVE: To assess the safety and effectiveness of
      transpupillary thermotherapy treatment of subfoveal choroidal neovascular
      membrane secondary to pathologic myopia. PATIENTS AND METHODS: Seventy-four
      patients (74 eyes) with pathologic myopia underwent transpupillary thermotherapy
      treatment using a 3.0-mm spot size, 1-minute duration, and 520-mW power delivered
      through a contact lens. Clinical evaluation included measurement of best
      corrected Snellen visual acuity, slit-lamp biomicroscopy, fundus color
      photography, and fluorescein angiography. RESULTS: Sixty-four eyes (86%) received
      one treatment session. Six eyes (8%) improved 0.1 logarithm of the minimum angle
      of resolution (LogMAR) visual acuity post-treatment, 10 eyes (13.5%) lost more
      than 0.2 LogMAR acuity, and another 10 eyes (13.5%) lost 0.1 LogMAR acuity. The
      remaining 48 eyes (65%) had unchanged visual acuity after the last follow-up
      visit. CONCLUSION: Transpupillary thermotherapy preserves vision in patients with
      choroidal neovascular membrane associated with pathologic myopia. Younger
      patients and eyes with higher refractive error are more likely to benefit from
      treatment.

PMID- 20128565
TI  - Effects of intravitreal erythropoietin therapy for patients with chronic and
      progressive diabetic macular edema.
AB  - BACKGROUND AND OBJECTIVE: To determine the effects of intravitreal injections of
      erythropoietin in eyes with severe, chronic diabetic macular edema, 5 eyes of 5
      patients underwent injections of rHuEPO alpha (EPO). PATIENTS AND METHODS: All
      eyes had progressive vision loss and persistent or worsening edema with prior
      multi-modal treatment. EPO (5U/50 microL) was injected intravitreally every 6
      weeks for three doses and followed for an additional 6 weeks with complete ocular
      examinations, fluorescein angiography, optical coherence tomography (OCT), and
      central field acuity perimetry. RESULTS: Visual acuity of all patients was
      subjectively improved by 3 or more lines in 3 eyes and 1 line in 2 eyes. Visual
      acuity improved to a larger extent than anatomic improvement by OCT. Clearing of
      hard exudates but only minor improvement in leakage on fluorescein angiography
      was observed. Improvement in vision occurred within 1 week after the first
      injection and was maintained until the end point of the current case series (at
      18 weeks after the first injection). CONCLUSION: This case series seems to show a
      short-term positive response to EPO for a specific group of patients with chronic
      diabetic macular edema who were unresponsive to currently available therapies.

PMID- 20128566
TI  - Intravitreal dexamethasone for diabetic macular edema: a pilot study.
AB  - BACKGROUND AND OBJECTIVE: To determine the response and safety profile of
      intravitreal dexamethasone in treating diabetic macular edema. PATIENTS AND
      METHODS: In this prospective pilot study, 12 eyes of 12 patients with diabetic
      macular edema were randomized to receive a single injection of 0.4 mg (n = 6) or
      0.8 mg (n = 6) of intravitreal dexamethasone. The outcome measures were changes
      in best-corrected visual acuity and central foveal thickness on optical coherence
      tomography. Side effects were monitored. RESULTS: The 3-month results were
      reported. In both dosage groups, there were transient improvements in best
      corrected visual acuity and central foveal thickness, but the changes were not
      significant at any time point (best-corrected visual acuity: P > or = 0.14;
      central foveal thickness: P > or = .08). No significant side effects were
      observed, except one eye developed a peak intraocular pressure of greater than 21
      mm Hg. CONCLUSION: A single injection of intravitreal dexamethasone (0.4 or 0.8
      mg) did not have significant beneficial effects on diabetic macular edema within
      3 months from injection in this small pilot study.

PMID- 20128567
TI  - Planned delayed relaxing retinotomy for proliferative vitreoretinopathy.
AB  - BACKGROUND AND OBJECTIVE: A program involving three operations-the first to
      reattach most of the retina under silicone oil, the second to reattach the
      remaining retina by planned delayed relaxing retinectomy (PDRR), and the third to
      remove silicone oil-was tested. PATIENTS AND METHODS: Review of electronic
      records of patients receiving PDRR for proliferative vitreoretinopathy (PVR). The
      primary end point was reattached retina without silicone oil. RESULTS: Eighty
      seven patients had PVR and 27 received PDRR (mean age: 66.6 years; mean follow
      up: 2.3 years). Ten patients had grade B PVR, 8 had CP1 to CP6, and 7 had CA2 to
      CA6. Twenty-four (89%) patients achieved a reattached retina without silicone
      oil. Mean logarithm of the minimum angle of resolution visual acuities were 1.41
      (standard deviation = 0.67) at presentation and 1.21 (standard deviation = 0.58)
      at final follow-up. Four patients had glaucoma and 1 had scleromalacia. The
      overall success rate for all patients with PVR was 85% reattached retina without
      oil tamponade. CONCLUSION: PDRR contributes to a high chance of reattached retina
      and oil removal in PVR.

PMID- 20128568
TI  - Optical coherence tomography findings in patients with retinitis pigmentosa and
      low visual acuity.
AB  - BACKGROUND AND OBJECTIVE: To study the morphological features of the macula of
      patients with retinitis pigmentosa and visual acuities of 20/200 or less as
      examined by optical coherence tomography. PATIENTS AND METHODS: In an
      observational case series study, 42 eyes (21 patients) with retinitis pigmentosa
      and visual acuities of 20/200 or less were evaluated by optical coherence
      tomography. RESULTS: Thirty-four (81%) eyes had atrophic retina (group 1) and 8
      (19%) eyes had cystoid macular edema (group 2). The mean visual acuity was
      20/1000 in group 1 and 20/300 in group 2. Epiretinal membrane was identified in
      27 (64.3%) eyes. CONCLUSION: Optical coherence tomography is a more sensitive
      method in detecting macular pathology and can help in selecting cases where
      treatment may be applied.

PMID- 20128569
TI  - Retinopathy of prematurity in very low birth weight infants and the potential
      protective role of indomethacin.
AB  - BACKGROUND AND OBJECTIVE: To describe clinical features of very low birth weight
      (VLBW) infants and examine the effect of indomethacin on the incidence of
      retinopathy of prematurity (ROP). PATIENTS AND METHODS: Medical records of all
      VLBW infants over a 4-year period were reviewed. Data regarding systemic and
      ophthalmic examinations were analyzed. RESULTS: Forty-seven infants with ROP were
      evaluated. Most infants had bilateral stage 1 or 2 disease extending 5 clock
      hours. Infants with ROP had younger mean gestational age, had lower gestational
      weight, and demonstrated higher incidence of diseases of prematurity. These
      infants were exposed to increased doses of surfactant and higher oxygen
      concentration for a prolonged duration given their immature pulmonary status.
      Independent predictors of ROP susceptibility also included length of
      hospitalization and Apgar score at 5 minutes. Patent ductus arteriosus was more
      common among infants with ROP. Approximately half of the infants who received one
      or two doses of indomethacin had ROP, but the ROP rate was decreased in infants
      who received three doses. CONCLUSION: Premature infants with younger gestational
      age, lower gestational weight, and severe morbidities were found to have an
      increased prevalence of ROP. Indomethacin treatment for patent ductus arteriosus
      may have a protective role in the development of severe ROP.

PMID- 20128570
TI  - Different patterns of fundus autofluorescence related to ABCA4 gene mutations in
      Stargardt disease.
AB  - BACKGROUND AND OBJECTIVE: Stargardt disease is a type of juvenile-onset macular
      dystrophy. The clinical presentation is characterized by macular atrophy and the
      presence of lipofuscin storage. The aim of this study was to investigate a
      possible correlation between different ABCA4 gene mutations and the
      autofluorescence pattern. PATIENTS AND METHODS: Twenty patients with Stargardt
      disease were examined for ABCA4 gene mutations and were administered fundus
      autofluorescence examinations. RESULTS: Autofluorescence imaging demonstrated
      different patterns. ABCA4 gene analysis exhibited 16 missense mutations, 4 stop
      mutations, 4 splicing mutations, 3 deletions, and 1 insertion randomly
      distributed in the two alleles. CONCLUSION: The presence of two severe mutations
      in the two alleles was associated with a larger atrophy of the retinal pigment
      epithelium in the macular area.

PMID- 20128571
TI  - Boundary detection errors on optical coherence tomography images in patients with
      diabetic retinopathy.
AB  - BACKGROUND AND OBJECTIVE: To study the incidence of boundary detection errors
      produced by optical coherence tomography measurements in patients with diabetic
      retinopathy. PATIENTS AND METHODS: One hundred sixteen eyes with diabetic
      retinopathy of 64 consecutive patients with diabetes mellitus were included in
      this retrospective study. The StratusOCT instrument (Carl Zeiss Meditec, Dublin,
      CA) with the macular thickness map protocol was used for the examinations. After
      data acquisition, each scan was analyzed using the retinal thickness (single eye)
      protocol to evaluate whether there was any misdetection of the retinal
      boundaries. RESULTS: Boundary detection errors were found in 35.3% of eyes. The
      majority of artifacts were those caused by hard exudates (41.5%), followed by
      cystoid macular edema (31.7%) and proliferation (17.0%). CONCLUSION: Occurrence
      of artifacts with optical coherence tomography measurements in cases of diabetic
      retinopathy is not a rare phenomenon and verification of quantitative
      measurements is strongly recommended.

PMID- 20128572
TI  - Stability of 35-mm scanners as used in ophthalmologic research.
AB  - BACKGROUND AND OBJECTIVE: To assess the consistency of digitization of 35-mm
      slides as practiced in ophthalmologic research and estimate the impact of
      variation on semi-automated retinal vessel width measurements. PATIENTS AND
      METHODS: A single retina slide was repeatedly digitized under various conditions
      on three scanner models. Average color levels were extracted from the resulting
      images, from which vessel widths were graded. The color channel level variations
      and possible correlation with width were analyzed. RESULTS: The Nikon 5000
      scanner (Nikon Corp., Tokyo, Japan) had average coefficients of variation of 0.4,
      2.3, and 0.5 for the red, green, and blue channel levels across all runs. The P
      values of the correlation between the red, green, and blue color channel levels
      and the width of the large retinal arteriole were .89, .27, and .58,
      respectively. CONCLUSION: The results suggest that the tested scanners digitize
      the 35-mm slides in a reliable manner without biasing the retinal vessel
      measurements.

PMID- 20128573
TI  - Ghost cell glaucoma after intravitreal bevacizumab for postoperative vitreous
      hemorrhage following vitrectomy for proliferative diabetic retinopathy.
AB  - BACKGROUND AND OBJECTIVE: To report the occurrence of ghost cell glaucoma after
      intravitreal injection of bevacizumab for the treatment of postoperative vitreous
      hemorrhage after vitrectomy for proliferative diabetic retinopathy (PDR).
      PATIENTS AND METHODS: Retrospective chart review from August 2006 to December
      2007. Patients who had postoperative vitreous hemorrhage after vitrectomy for PDR
      and received an intravitreal injection of bevacizumab were enrolled in the study.
      RESULTS: Eight eyes of 8 patients (mean age: 46 years) were included. After
      intravitreal injection of bevacizumab, 4 (50%) eyes had clearance of vitreous
      hemorrhage. Three eyes developed ghost cell glaucoma within 1 week after
      intravitreal injection of bevacizumab. Of these, intraocular pressure was
      controlled in 1 eye through the use of anti-glaucoma medication, whereas the
      other 2 eyes needed surgical intervention to lower intraocular pressure and
      subsequently clear the vitreous hemorrhage. CONCLUSION: Intravitreal injection of
      bevacizumab may accelerate the clearance of postoperative vitreous hemorrhage in
      cases of PDR. However, a high incidence of ghost cell glaucoma was observed.
      Caution should be exercised when administering an intravitreal injection of
      bevacizumab for a postoperative vitreous hemorrhage after vitrectomy for PDR.

PMID- 20128574
TI  - In vivo fluorescence mode confocal microscopy of subepithelial tissues in
      glaucoma filtering blebs.
AB  - BACKGROUND AND OBJECTIVE: The miniaturization of confocal imaging technology has
      resulted in the development of a handheld confocal microscope probe capable of
      fluorescence mode imaging. Findings in the subepithelial tissues of glaucoma
      filtering blebs using this novel approach for proof of concept are described.
      PATIENTS AND METHODS: A fiberoptic confocal imaging probe using an illumination
      wavelength of 488 nm was applied to the bleb surface of 11 eyes after topical or
      subconjunctival administration of sodium fluorescein. The imaging plane was moved
      to the subepithelial region and multiple images from multiple bleb regions were
      captured at a resolution of 1,024 x 1,024 pixels per square inch. RESULTS: High
      quality images of the bleb wall structure, vasculature, and superficial sclera
      were obtained and demonstrated subcellular detail. Lateral resolution was between
      1 and 1.5 microm and axial resolution was approximately 30 microm. Identifiable
      structures in the failing blebs included vasculature (including individual
      erythrocytes, pericytes, and vascular endothelium); microcystic structures; and
      cells within the Tenon's tissue, some of which resembled fibroblasts. CONCLUSION:
      Fluorescence mode imaging of ocular subsurface detail is a viable and promising
      tool for assessment of wound healing and other processes in trabeculectomy blebs.
      The ability to image fluorophores creates the possibility of functional imaging.

PMID- 20128575
TI  - Characteristics of optic nerve head drusen on optical coherence tomography
      images.
AB  - BACKGROUND AND OBJECTIVE: To describe the characteristics of optic nerve head
      drusen in optical coherence tomography (OCT) images. PATIENTS AND METHODS: Cross
      sectional images of the optic nerve were obtained in seven patients with optic
      nerve head drusen with Stratus and spectral-domain OCT (Carl Zeiss Meditec,
      Dublin, CA). These were compared to optic disc photographs, autofluorescence, and
      echography images. For comparison, these tests were performed on four patients
      with papilledema and three patients with small optic discs. RESULTS: Optic nerve
      head drusen typically elevated the disc surface and appeared as an optically
      empty cavity, sometimes with a perceptible reflection from the posterior surface.
      The disc surface was also elevated in cases of papilledema, but had a strong
      anterior reflectance behind which there was no visible structure. The surface of
      the small optic nerves was slightly elevated, but with less anterior reflectance.
      CONCLUSION: Optic nerves with drusen showed features in these OCT images that
      were distinct from cases of papilledema or small optic discs.

PMID- 20128576
TI  - Comparison of the outcomes of limbal-based trabeculectomy with and without anchor
      sutures.
AB  - BACKGROUND AND OBJECTIVE: To retrospectively evaluate the efficacy and safety of
      limbal-based trabeculectomy with anchor sutures compared to standard limbal-based
      trabeculectomy. Limbal-based trabeculectomy was performed with a new technique
      using anchor sutures, which involved tying the conjunctiva to the sclera at a
      deep fornix incision to prevent bleb localization induced by slippage of the
      conjunctival suture scar toward the scleral flap. PATIENTS AND METHODS: In this
      retrospective, comparative, interventional case series, 45 eyes that underwent
      limbal-based trabeculectomy with anchor sutures and 27 eyes that underwent
      standard limbal-based trabeculectomy were analyzed (primary surgery). RESULTS: At
      a target intraocular pressure of 15 mm Hg, the 3-year survival rate using Kaplan
      Meier analysis was 76.2% in the limbal-based trabeculectomy with anchor sutures
      group and 55.6% in the standard limbal-based trabeculectomy group. Bleb
      morphology analysis using the Moorfields Bleb Grading System showed that blebs in
      the limbal-based trabeculectomy with anchor sutures group were more diffused than
      those in the standard limbal-based trabeculectomy group. CONCLUSION: Limbal-based
      trabeculectomy with anchor sutures appears to be an effective method for
      decreasing intraocular pressure and improving morphology of blebs.

PMID- 20128577
TI  - Retinal nerve fiber layer thickness after a single attack of primary acute angle
      closure glaucoma measured with optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: After a single unilateral acute primary angle-closure
      glaucoma attack, retinal nerve fiber layer (RNFL) may be thinned. The current
      study measured the RNFL thickness using optical coherence tomography in eyes with
      normal visual fields after recovery from a single attack of acute primary angle
      closure glaucoma. PATIENTS AND METHODS: Twenty-one patients and age-matched
      control subjects underwent optical coherence tomography scanning after recovery
      from a single unilateral acute primary angle-closure glaucoma attack. Data from
      the affected eyes, normal fellow eyes, and control subjects were compared.
      RESULTS: Average RNFL thickness was 91.3 +/- 16.4 microm in the affected eyes,
      100.1 +/- 16.4 microm in the fellow eyes, and 100.2 +/- 16.7 microm in the
      control eyes. Significant thinning was present in the affected eyes compared to
      the fellow eyes (P = .001) and the control eyes (P = .04). CONCLUSION: RNFL
      thickness was found to be significantly thinner in the eyes with angle-closure
      glaucoma.

PMID- 20128578
TI  - The impact of anti-inflammatory therapy on intraocular pressure reduction
      following selective laser trabeculoplasty.
AB  - BACKGROUND AND OBJECTIVE: To determine whether the use of postoperative topical
      anti-inflammatory therapy affects the intraocular pressure (IOP)-lowering
      efficacy of selective laser trabeculoplasty in eyes with primary open-angle
      glaucoma. PATIENTS AND METHODS: In this prospective, randomized, observer-masked
      study, 25 participants with primary open-angle glaucoma following bilateral 360
      degrees selective laser trabeculoplasty used prednisolone acetate 1% four times
      daily in one randomly selected eye for 1 week. IOP was assessed at baseline and 1
      week, 1 month, and 3 months after selective laser trabeculoplasty. RESULTS:
      Baseline IOP and selective laser trabeculoplasty treatment parameters were
      comparable in both groups. Mean IOP was similar in eyes that did and did not
      receive steroid therapy at 1 week (17.0 vs 16.3 mm Hg, respectively, P = .613), 1
      month (16.8 vs 16.2 mm Hg, respectively; P = .571), and 3 months (16.0 vs 15.8 mm
      Hg, respectively; P = .819). CONCLUSION: A 1-week course of topical prednisolone
      acetate 1% four times daily did not affect the IOP-lowering effect of selective
      laser trabeculoplasty in eyes with primary open-angle glaucoma.

PMID- 20128579
TI  - Phacoemulsification with intraocular lens implantation in juvenile idiopathic
      arthritis.
AB  - BACKGROUND AND OBJECTIVE: To evaluate outcomes of phacoemulsification cataract
      surgery with intraocular lens (IOL) implantation in children and adults with
      juvenile idiopathic arthritis-associated uveitis. PATIENTS AND METHODS: Charts of
      7 patients (10 eyes) with juvenile idiopathic arthritis-associated uveitis who
      had phacoemulsification cataract surgery between December 2002 and March 2005
      were analyzed. RESULTS: Ten eyes of 7 patients had phacoemulsification with IOL
      implantation done by a single surgeon. A heparin surface modified IOL was used in
      7 eyes and a foldable acrylic IOL was used in 3 eyes. At final follow-up, 70% of
      eyes had a visual acuity of 20/40 or better and 30% had improved visual acuity to
      20/60. Posterior capsular opacification was found in 2 eyes and anterior capsular
      fibrosis in 1 eye. CONCLUSION: Keys to success following cataract surgery in
      juvenile idiopathic arthritis are the age of the child, the absence of amblyopia,
      and strict preoperative and postoperative control of inflammation.

PMID- 20128580
TI  - Comparison of torsional and microburst longitudinal phacoemulsification: a
      prospective, randomized, masked clinical trial.
AB  - BACKGROUND AND OBJECTIVE: To compare intraoperative performance and postoperative
      outcome of three phacoemulsification technologies in patients undergoing
      microcoaxial phacoemulsification through 2.2-mm corneal incisions. PATIENTS AND
      METHODS: The prospective, randomized, single-masked study included 360 eyes
      randomly assigned to torsional (Infiniti Vision System; Alcon Laboratories, Fort
      Worth, TX), microburst with longitudinal (Infiniti), or microburst with
      longitudinal (Legacy Everest, Alcon Laboratories) ultrasound. Assessments
      included surgical clock time, fluid volume, and intraoperative complications,
      central corneal thickness on day 1 and months 1 and 3 postoperatively, and
      endothelial cell density at 3 months postoperatively. Comparisons among groups
      were conducted. RESULTS: Torsional ultrasound required significantly less
      surgical clock time and fluid volume than the other groups. There were no
      intraoperative complications. Change in central corneal thickness and endothelial
      cell loss was significantly lower in the torsional ultrasound group at all
      postoperative visits (P < .001, Kruskal-Wallis test) compared to microburst
      longitudinal ultrasound modalities. CONCLUSION: Torsional ultrasound demonstrated
      quantitatively superior intraoperative performance and showed less increase in
      corneal thickness and less endothelial cell loss compared to microburst
      longitudinal ultrasound.

PMID- 20128581
TI  - Assessment and comparison of anterior chamber dimensions using various imaging
      techniques.
AB  - BACKGROUND AND OBJECTIVE: To assess and compare the horizontal dimensions of the
      anterior chamber by different anterior segment imaging techniques. PATIENTS AND
      METHODS: Eighty eyes of 40 patients without any ocular disease or previous ocular
      surgery were recruited and three consecutive measurements of internal anterior
      chamber diameter and white-to-white distance (WTW) parameters were determined.
      RESULTS: Mean internal anterior chamber diameter was 11.80 +/- 0.39, 11.56 +/-
      0.47, and 11.61 +/- 0.58 mm with Visante-OCT, SL-OCT, and Pentacam, respectively.
      Mean WTW distance was 11.87 +/- 0.35 and 11.65 +/- 0.32 mm by IOLMaster and
      OrbscanIIz, respectively. There was no significant difference between Visante-OCT
      and Pentacam, IOLMaster, and OrbscanIIz (P = .125, .918, and .314). However,
      detection of mean internal anterior chamber diameter was significantly greater by
      Visante-OCT than SL-OCT (P = .026). All devices displayed a high intrasession
      repeatability (repeated measured ANOVA, P > .05). CONCLUSION: Internal anterior
      chamber diameter measurements using Visante-OCT, SL-OCT, and Pentacam, and WTW
      measurements using IOLMaster and OrbscanIIz were easy to handle and demonstrated
      good repeatability. Although similar results of horizontal anterior chamber
      diameter were determined by Visante-OCT, Pentacam, IOLMaster, and OrbscanIIz, the
      inter-device differences should be considered during clinical practice.

PMID- 20128582
TI  - Ocular and systemic morbidity profile in mass formic acid injuries.
AB  - BACKGROUND AND OBJECTIVE: A report on formic acid-induced ocular and systemic
      injuries. PATIENTS AND METHODS: Forty-two passengers (84 eyes) with formic acid
      burns following a tanker and bus collision were evaluated and treated. The
      severity of ocular chemical injury was assessed using the Roper-Hall
      classification. Standard protocol for management of ocular chemical burns was
      adopted in all patients. Immediate irrigation of the eyes was done with tap water
      and all patients received frequent topical steroids, cycloplegics, and
      lubricating eye drops. Systemic injuries were evaluated and managed collectively
      by plastic and orthopedic surgeons and internists. RESULTS: On presentation, 48
      (57.14%) eyes had grade 0, 13 (15.48%) eyes had grade I, 16 (19.1%) eyes had
      grade II, 3 (3.57%) eyes had grade III, and 4 (4.76%) eyes had grade IV chemical
      injuries. Thirty patients (71.43%) had superficial and 12 (28.57%) had deep skin
      burns. One (2.38%) patient died due to severe pulmonary edema and 6 (14.29%)
      patients had severe pulmonary complications requiring oxygen treatment. Seventy
      two (87.8%) eyes healed without residual sequelae, 10 (12.2%) eyes had nebulo
      macular corneal opacities, and 2 (2.44 %) eyes developed secondary glaucoma and
      dry eye. CONCLUSION: Formic acid injuries can lead to a significant ocular and
      systemic morbidity. Immediate ocular and systemic management is necessary to
      reduce morbidity and mortality. Strict regulations are needed for the
      transportation of dangerous chemicals to prevent accidental chemical injuries.

PMID- 20128583
TI  - Corneal wound architecture and integrity after torsional and mixed
      phacoemulsification: evaluation of standard and microincisional coaxial
      techniques.
AB  - BACKGROUND AND OBJECTIVE: To compare the effects of torsional and mixed
      ultrasound on clear corneal incision architecture, wound integrity, and
      apposition using standard (2.75 mm) and microincisional (2.2 mm) coaxial
      phacoemulsification. SUBJECTS AND METHODS: Twenty human cadaver eyes (4 groups of
      5 eyes) underwent simulated coaxial phacoemulsification for 45 seconds of
      ultrasound time (group 1 = 2.75 mm, 100% torsional; group 2 = 2.2 mm, 70%
      torsional; group 3 = 2.2 mm, 100% torsional; group 4 = 2.2 mm, mixed ultrasound).
      All phacoemulsification settings were kept constant across each group. Following
      phacoemulsification, intraocular pressure (IOP) was cyclically raised and lowered
      from 0 to 125 mm Hg. Two eyes from each group had India ink placed over the wound
      and were observed for leakage and for histopathologic examination. Eyes not
      exposed to India ink (three eyes of each group) were examined using anterior
      segment optical coherence tomography (OCT) and scanning electron microscopy
      (SEM). RESULTS: Wound leakage was evident in one eye from group 1 and no eyes
      from the other three groups. Histopathologic examination revealed no India ink
      penetration in any of the eyes studied. Anterior segment OCT showed good wound
      apposition in each group. SEM demonstrated partially compromised endothelium and
      Descemet's membrane in all eyes studied from each group. CONCLUSION: No
      differences in corneal wound architecture and integrity were observed. Torsional
      and mixed ultrasound settings do not appear to induce any adverse effects on
      corneal wound architecture and integrity in standard and microincisional coaxial
      phacoemulsification techniques.

PMID- 20128584
TI  - Real-time ultrasound elastographic imaging of ocular and periocular tissues: a
      feasibility study.
AB  - BACKGROUND AND OBJECTIVE: This study examines the value of ultrasound
      elastography for the examination of ocular and periocular structures. SUBJECTS
      AND METHODS: Five patients, aged 22 to 75 years, who each had one blind eye were
      included. Patients underwent ultrasound elastography of their blind eye and
      periocular tissues using a 7-13 MHz probe. Strain grayscale and color-coded
      elastographic maps were recorded. In the former, a quantitative assessment of
      signal intensity (corresponding to elastic properties) for specific anatomical
      structures was performed. RESULTS: Anterior vitreous displayed intermediate
      elasticity, whereas posterior vitreous displayed low elasticity. Medial and
      lateral rectus muscle elasticity was higher in primary position than in adduction
      or abduction. CONCLUSION: The pattern of elastic imaging in the vitreous cavity
      could be attributed to posterior vitreous detachment, whereas that of medial and
      lateral rectus muscles may be related to the level of muscle fiber strain.

PMID- 20128585
TI  - Matrix isolation infrared spectroscopic and density functional theoretical study
      of the reactions of scandium and yttrium monoxides with monochloromethane.
AB  - Reactions of scandium and yttrium monoxide molecules (ScO and YO) with
      monochloromethane have been studied in solid argon by infrared absorption
      spectroscopy and density functional theoretical calculations. The metal monoxide
      molecules were prepared by laser-evaporation of bulk metal oxide targets. The
      results show that the ground state scandium and yttrium monoxide molecules
      reacted with CH(3)Cl to form two MO(CH(3)Cl) (M = Sc, Y) complex isomers
      spontaneously on annealing. Broad-band UV-visible irradiation initiated the
      addition of the Cl-C bond to the M=O bond to form the CH(3)OMCl molecule and the
      addition of the C-H bond to the M=O bond to give the CH(2)ClMOH isomer, both of
      which are more stable than the MO(CH(3)Cl) complex structures. The CH(2)ClMOH
      molecule was predicted to involve agnostic interaction between the chlorine atom
      and the metal atom.

PMID- 20128586
TI  - Molecular structures and energetics of the (ZrO(2))(n) and (HfO(2))(n) (n = 1-4)
      clusters and their anions.
AB  - The group IVB transition-metal dioxide clusters and their anions, (MO(2))(n) and
      (MO(2))(n)(-) (M = Zr, Hf; n = 1-4), are studied with coupled cluster (CCSD(T))
      theory and density functional theory (DFT). Similar to the results for M = Ti,
      these oxide clusters have a number of low-lying isomeric structures, which can
      make it difficult to predict the ground electronic state especially for the
      anion. Electron affinities for the low-lying structures are calculated and
      compared with those for M = Ti. Electron affinities of these clusters depend
      strongly on the cluster structures. Anion photoelectron spectra are calculated
      for the monomer and dimer and demonstrate the possibility for structural
      identification at a spectral line width of <or=0.05 eV. Electron excitation
      energies from the low-lying states to the singlet and triplet excited states are
      calculated self-consistently, as well as by the time-dependent DFT and equation
      of-motion coupled cluster (EOM-CCSD) methods. The calculated excitation energies
      are compared to the band energies of bulk oxides, indicating that the excitation
      energy is not yet converged for n = 4 for these clusters. The excitation energies
      of the low-lying isomeric clusters are less than the bulk metal oxide band gaps
      and suggest that these clusters could be useful photocatalysts with a visible
      light source.

PMID- 20128587
TI  - Indirect photodegradation of clethodim in aqueous media. byproduct identification
      by quadrupole time-of-flight mass spectrometry.
AB  - Aqueous photolysis of clethodim herbicide in the presence of natural substances
      such as humic acids (HA), nitrate, and Fe(III) ions has been investigated. The
      photodegradation rate of clethodim was retarded in the presence of HA compared to
      ultrapure water, while nitrate ions had no effect. On the other hand, water
      containing different concentrations of Fe(III) ions enhanced degradation of this
      herbicide. Clethodim transformation gave rise to the formation of nine
      byproducts, some of them, to the best of our knowledge, described for the first
      time in this work. The identification of these photoproducts has been
      accomplished by coupling liquid chromatography to quadrupole time-of-flight mass
      spectrometry. The main transformation reactions observed for clethodim were
      photoisomerization to the Z-isomer, S-oxidation of E- and Z-clethodim isomers
      giving rise to sulfoxide diastereoisomers, reduction of the oxime moiety to yield
      clethodim imine, oxidative cleavage of the C-S bond, and S-oxidation of clethodim
      imine leading to the formation of imine ketone and imine sulfoxide.

PMID- 20128588
TI  - Antrocamphin A, an anti-inflammatory principal from the fruiting body of
      Taiwanofungus camphoratus , and its mechanisms.
AB  - The fungus Taiwanofungus camphoratus is commonly used for medicinal purposes in
      Taiwan. It is used as a detoxicant for food poisoning and considered to be a
      precious folk medicine for hepatoprotection and anti-inflammation. In this study,
      a lipopolysaccaride (LPS)-challenged ICR mouse acute inflammation model and a LPS
      induced macrophage model were used to evaluate the anti-inflammatory activity of
      T. camphoratus. Ethanol extract of T. camphoratus significantly inhibited
      expression of iNOS and COX-2 in the liver of LPS-challenged acute inflammatory
      mice. The ethyl acetate fraction and its isolated compound, antrocamphin A,
      significantly suppressed nitrite/nitrate concentration in LPS-challenged RAW
      264.7 cells. Antrocamphin A showed potent anti-inflammatory activity by
      suppressing pro-inflammatory molecule release via the down-regulation of iNOS and
      COX-2 expression through the NF-kappaB pathway. This study, therefore, first
      demonstrates the bioactive compound of T. camphoratus and illustrates the
      mechanism by which it confers its anti-inflammatory activity.

PMID- 20128589
TI  - Modeling and optimization of phenylalanine ammonia lyase stabilization in
      recombinant Escherichia coli for the continuous synthesis of l-phenylalanine on
      the statistical-based experimental designs.
AB  - Some approaches for improving recombinant phenylalanine ammonia lyase (PAL)
      stability in Escherichia coli during the enzymatic methods of l-phenylalanine (l
      Phe) production were developed following preliminary studies by means of
      statistical-based experiment designs (response surface method). The traditional
      non-statistical technology was used to screen four critical factors for PAL
      stability during the bioconversion process, viz., glycerin, sucrose, 1,4
      dithiothreitol (DTT), and MgSO(4). The central composite design (CCD) was applied
      to optimize the combined effect of critical factors for recombinant PAL stability
      and understand the relationship between the factors and PAL stability. The
      optimum values for testing variables were 13.04 mM glycerin, 1.87 mM sucrose,
      4.09 mM DTT, and 69 mM Mg(2+). A second-order model equation was suggested and
      then validated experimentally. The model adequacy was very satisfactory because
      the coefficient of determination was 0.88. The maximum PAL activity was retained
      as 67.73 units/g after three successive cycles of bioconversion. In comparison to
      initial PAL activity, the loss of PAL activity was only 22%. PAL activity was
      enhanced about 23% in comparison to the control (without any stabilizer
      additives). PAL stability was significantly improved during successive
      bioconversion. The results obtained here verified the effectiveness of the
      applied methodology and may be helpful for l-Phe production on an industrial
      scale.

PMID- 20128590
TI  - Theoretical investigation of the oxidation of propane by FeO(+).
AB  - We report herein a comprehensive theoretical study of the oxidation of propane by
      FeO(+) on both the sextet and quartet potential energy surfaces (PESs) using
      density functional theory. The geometries and energies of all the stationary
      points involved are located. Interaction of FeO(+) with propane could account for
      four types of encounters (i.e., alpha,beta,gamma-, 2alpha,beta-, 3alpha-eta(3),
      and 2alpha,2gamma-eta(4)) complexes. Various mechanisms leading to the loss of
      CH(3), H(2)O, C(3)H(7)OH (H(2)O + C(3)H(6)), and C(3)H(6) are analyzed in terms
      of the topology of the PES. The reaction of FeO(+) with propane involves initial
      C-H activation, while initial C-C activation is indeed unlikely to be important.
      The loss of CH(3) takes place adiabatically on the sextet PES via the simple
      C(alpha)-to-O H shift from eta(4)-OFe(+)(C(3)H(8)) followed by CH(3) shift. The
      C(3)H(7)OH elimination proceeds via direct C(alpha)-to-O H shift followed by C-O
      coupling, while the loss of H(2)O, C(3)H(6), and (H(2)O + C(3)H(6)) proceeds via
      the alpha,beta-H and beta,alpha-H abstraction mechanisms from all the eta(3)
      complexes. The most favorable channel is the alpha,beta-H abstraction mechanism
      for the H(2)O loss because it not only is energetically and dynamically favorable
      but also has a high crossing probability between the sextet and quartet PESs. The
      computational results are in concert with the available experimental information
      and add new insight into the details of the individual elementary steps.

PMID- 20128591
TI  - Gold nanoparticles and imaging mass spectrometry: double imaging of latent
      fingerprints.
AB  - Latent fingerprint (LFP) detection is a top-priority task in forensic science. It
      is a simple and effective means for the identification of individuals.
      Development of nanomaterials which maximize the surface interaction with
      endogenous substances on the ridges to enhance the contrast of the fingerprints
      is an important application of nanotechnology in LFP detection. However, most
      developments in this area have mainly focused on the visualization of the
      physical pattern of the fingerprints and failed to explore the molecular
      information embedded in LFPs. Here, we have integrated certain distinctive
      properties of gold nanoparticles (AuNPs) with imaging mass spectrometry for both
      the visualization and molecular imaging of LFPs. Two contrasting colors (blue and
      pink), arising from different surface plasmon resonance (SPR) bands of the AuNPs,
      reveal the optical images of LFPs. The laser desorption/ionization property of
      the AuNPs allows the direct analysis of endogenous and exogenous compounds
      embedded in LFPs and imaging their distributions without disturbing the
      fingerprint patterns. The simultaneous visualization of LFP and the recording of
      its molecular images not only provide evidence on individual identity but also
      resolve overlapping fingerprints and detect hazardous substances.

PMID- 20128592
TI  - China: forward to the green pesticides via a basic research program.
AB  - The 973 Program is China's keystone national research program established to
      support basic research in natural and physical sciences. In addition to promoting
      the development of core technology and scientific infrastructure needed to enable
      China to meet the social and economic challenges of the 21st century, the
      training and mentoring of the new generation of China's young scientists are also
      important objectives of this national program. The green chemical pesticide
      research program is a part of the 973 Program. The main objectives of stage 1 of
      the green chemical pesticide research program (2003-2008) are to establish
      China's capability to conduct basic research in the discovery of "green" crop
      protection chemicals that are not only novel in mode of action and highly
      selective to pest species that are unique to China's agricultural situation but
      also possess favorable environmental and human hazard and risk potentials. The
      target-based discovery strategy was selected as the main discovery platform. This
      strategy not only provided this research program the best chance to discover new
      products but also provided members of this research team opportunities to
      establish core technologies in chemoinformatics/computation-aided pesticide
      design using QSAR, QAAR, sensitive and selective bioassay methodology,
      combinatorial synthesis, hit to lead optimization, and biological targets that
      were derived from resistance-AChE, IGR, nAChR, etc. On the basis of the learning
      from stage 1, stage 2 (2010-2014) of this program will focus on the molecular
      target-oriented innovation of green chemical pesticides. This commentary presents
      key learnings and accomplishments from the stage 1 of China's green chemical
      pesticide research program. It is hoped that this information will stimulate
      further constructive collaborations between pesticide scientists from China and
      abroad.

PMID- 20128593
TI  - Biological response of hepatomas to an extract of Fagopyrum esculentum M.
      (buckwheat) is not mediated by inositols or rutin.
AB  - Buckwheat contains d-chiro-inositol (D-CI) and myo-inositol (MI), possible
      insulin-mimetic compounds; thus, this study investigated the insulin-mimetic
      activities of a buckwheat concentrate (BWC), D-CI, and MI on insulin signal
      transduction pathways and glucose uptake with H4IIE rat hepatoma cells. BWC
      stimulated phosphorylation of p42/44 extracellular-related kinase (p42/44 ERK)
      and its downstream target, p70(S6K), on Thr(421). In contrast, D-CI, MI, rutin,
      or its agylcone form, quercetin, did not activate these signal transduction
      proteins. Phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK),
      another target of insulin, was also up-regulated upon BWC treatment. The effects
      of BWC on glucose uptake were subsequently investigated using H4IIE cells.
      Insulin and D-CI stimulated glucose uptake, whereas BWC inhibited basal and
      insulin-stimulated glucose uptake. Although results from this work suggest that
      BWC has insulin-mimetic effects on select protein phosphorylation events in H4IIE
      cells, D-CI and MI were not the active components responsible for the observed
      effects. The inhibition of glucose uptake by BWC suggests that buckwheat may
      affect hepatic glucose metabolism, possibly by inhibiting glucose flux.
      Furthermore, the fact that D-CI and MI stimulated glucose uptake in H4IIE cells
      suggests that other compounds are responsible for inhibition of glucose uptake by
      BWC.

PMID- 20128594
TI  - Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2
      pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversible
      peroxisome proliferator-activated receptor delta (PPARdelta) antagonist.
AB  - 4-Chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide 3 (GSK3787)
      was identified as a potent and selective ligand for PPARdelta with good
      pharmacokinetic properties. A detailed binding study using mass spectral analysis
      confirmed covalent binding to Cys249 within the PPARdelta binding pocket. Gene
      expression studies showed that pyridylsulfone 3 antagonized the transcriptional
      activity of PPARdelta and inhibited basal CPT1a gene transcription. Compound 3 is
      a PPARdelta antagonist with utility as a tool to elucidate PPARdelta cell biology
      and pharmacology.

PMID- 20128595
TI  - Design and synthesis of potent and selective BACE-1 inhibitors.
AB  - Highly potent BACE-1 protease inhibitors have been developed from an inhibitors
      containing a hydroxyethylene (HE) core displaying aryloxymethyl or
      benzyloxymethyl P1 side chain and a methoxy P1' side chain. The target molecules
      were synthesized in good overall yields from chiral carbohydrate starting
      materials. The inhibitors show high BACE-1 potency and good selectivity against
      cathepsin D, where the most potent inhibitor furnishes BACE-1 K(i) << 1 nM and
      displays >1000-fold selectivity over cathepsin D.

PMID- 20128596
TI  - Synthesis and biological evaluation of polysulfated oligosaccharide glycosides as
      inhibitors of angiogenesis and tumor growth.
AB  - A series of polysulfated penta- and tetrasaccharide glycosides containing alpha(1
      ->3)/alpha(1-->2)-linked mannose residues were synthesized as heparan sulfate
      (HS) mimetics and evaluated for their ability to inhibit angiogenesis. The
      compounds bound tightly to angiogenic growth factors (FGF-1, FGF-2, and VEGF) and
      strongly inhibited heparanase activity. In addition, the compounds exhibited
      potent activity in cell-based and ex vivo assays indicative of angiogenesis, with
      tetrasaccharides exhibiting activity comparable to that of pentasaccharides.
      Selected compounds also showed good antitumor activity in vivo in a mouse
      melanoma (solid tumor) model resistant to the phase III HS mimetic 1
      (muparfostat, formerly known as PI-88). The lipophilic modifications also
      resulted in reduced anticoagulant activity, a common side effect of HS mimetics,
      and conferred a reasonable pharmacokinetic profile in the rat, as exemplified by
      the sulfated octyl tetrasaccharide 5. The data support the further investigation
      of this class of compounds as potential antiangiogenic, anticancer therapeutics.

PMID- 20128597
TI  - Dinuclear [{Fe(NO)2}(10)-{Fe(NO)2}(10)] dinitrosyl iron complex with thiolate-CO
      bridged ligands.
AB  - Air-sensitive complexes {Fe(NO)(2)}(9)-{Fe(NO)(2)}(9) [Fe(mu-SC(6)H(4)-o
      N(CH(3))(2))(NO)(2)](2) (1), {Fe(NO)(2)}(9)-{Fe(NO)(2)}(10) [Fe(mu-SC(6)H(4)-o
      N(CH(3))(2))(NO)(2)](2)(-) (2), the anionic {Fe(NO)(2)}(10) [(SC(6)H(4)-o
      N(CH(3))(2))Fe(NO)(2)](-) (3), and the anionic {Fe(NO)(2)}(10)-{Fe(NO)(2)}(10)
      [Fe(NO)(2)(mu-SC(6)H(4)-o-N(CH(3))(2))(mu-CO)Fe(NO)(2)](-) (4) with mixed CO
      thiolate-bridged ligands were synthesized. All complexes were characterized by
      IR, UV-vis, electron paramagnetic resonance, and single-crystal X-ray
      diffraction. The interconversions among these complexes were demonstrated. The
      interconversion between complexes 1 and 2 is accomplished by reduction and
      oxidation. Complex 3 adapts a {Fe(NO)(2)}(10) electronic structure with a N/S
      ligation mode and serves as a donor reagent of the {Fe(NO)(2)}(10) moiety.
      {Fe(NO)(2)}(10)-{Fe(NO)(2)}(10) complex 4 possesses the butterfly-like [Fe(mu
      S)(mu-C)Fe] core with a shorter Fe...Fe distance of 2.5907(5) A attributed to the
      shorter Fe-S and Fe-C bond distances.

PMID- 20128598
TI  - Axial ligand orientations in a distorted porphyrin macrocycle: synthesis,
      structure, and properties of low-spin bis(imidazole)iron(III) and iron(II)
      porphyrinates.
AB  - We have reported here, for the first time, the parallel and perpendicular
      orientation preferences of two planar and unhindered imidazoles as axial ligands
      (L) while coordinated toward iron(III) and iron(II) porphyrins, respectively, in
      a nonplanar porphyrinic environment. The synthesis and characterization of low
      spin Fe(III)(tn-OEP)(L)(2) x ClO(4) and Fe(II)(tn-OEP)(L)(2) are reported.
      Fe(III)(tn-OEP)(L)(2) x ClO(4) shows rhombic electron paramagnetic resonance
      (EPR) spectra (at 77 K) in both solid and solution phases that are very
      characteristic for low-spin (S = 1/2) iron porphyrins with two axial imidazole
      ligands aligned parallel to each other. Single-point energy calculation is also
      performed on Fe(III)(tn-OEP)(1-MeIm)(2)(+) using density functional theory (DFT),
      which shows that the relative parallel orientations of two 1-MeIm are more stable
      than the perpendicular orientations. X-ray structures of Fe(II)(tn-OEP)(1
      MeIm)(2) and Fe(II)(tn-OEP)(1-MeIm)(2).THF are reported that demonstrate, for the
      first time, the near-perpendicular axial ligand orientation (80.9 and 89.8
      degrees, respectively) for iron(II) porphyrins in a distorted macrocyclic
      environment. Even starting from parallel axial orientations of 1-MeIm, geometry
      optimization using DFT converged well to the perpendicular axial alignment with a
      82.54 degree dihedral angle, which is in close agreement with experiment. This is
      in sharp contrast to all earlier reports, in which sterically crowded imidazole
      (such as 2-MeIm) or a nearly planar porphyrin core with a "picket fence"
      environment that restricts the rotation of the axial ligands is required for
      perpendicular orientation. Electrochemical data obtained from a cyclic
      voltammetric study for Fe(II)(tn-OEP)(L)(2) reveal one-electron oxidation at very
      high positive potential, which readily explains why the complexes are so stable
      in air. Bulk oxidation of Fe(II)(tn-OEP)(1-MeIm)(2) at a constant potential of
      0.69 V in dichloromethane with 0.1 M tetrabutylammonium perchlorate as the
      supporting electrolyte generates Fe(III)(tn-OEP)(1-MeIm)(2) x ClO(4), which has
      the same EPR spectrum and which upon reduction at 0.29 V regenerates Fe(II)(tn
      OEP)(1-MeIm)(2) again. Thus, we have demonstrated here, for the first time, that
      iron(II) and iron(III) porphyrinates with two planar and unhindered axial
      imidazoles have different orientation preferences in a nonplanar porphyrinic
      environment.

PMID- 20128599
TI  - Does the MgO(100)-support facilitate the reaction of nitrogen and hydrogen
      molecules catalyzed by Zr2Pd2 clusters? A computational study.
AB  - Reactions of the "naked" and MgO(100) supported Zr(2)Pd(2) cluster with nitrogen
      and four hydrogen molecules were studied at the density functional level using
      the periodic slab approach (VASP). It was shown that adsorption of the Zr(2)Pd(2)
      cluster on the MgO(100) surface does not change its gas-phase geometry and
      electronic structure significantly. In spite of this the N(2) coordination to the
      MgO(100)-supported Zr(2)Pd(2) cluster, I/MgO, is found to be almost 30 kcal/mol
      less favorable than for the "naked" one. The addition of the first H(2) molecule
      to the resulting II/MgO, that is, II/MgO + H(2) --> IV/MgO reaction, proceeds
      with a relatively small, 9.0 kcal/mol, barrier and is exothermic by 8.3 kcal/mol.
      The same reaction for the "naked" Zr(2)Pd(2) cluster requires a slightly larger
      barrier (10.1 kcal/mol) and is highly exothermic (by 23.3 kcal/mol). The
      interaction of the H(2) molecule with the intermediate IV/MgO (i.e., the second
      H(2) molecule addition to II/MgO) requires larger energy barrier, 23.3 kcal/mol
      vs 8.8 kcal/mol for the "naked" cluster, and is exothermic by 20.5 kcal/mol (vs
      18.2 kcal/mol reported for the "naked" Zr(2)Pd(2) cluster). The addition of the
      H(2) molecule to VI/MgO and VI (i.e., the third H(2) molecule addition to II/MgO
      and II, respectively) requires similar barriers, 12.0 versus 16.8 kcal/mol,
      respectively, but is highly exothermic for the supported cluster compared to the
      "naked" one, 13.6 versus 0.1 kcal/mol. The addition of the fourth H(2) molecule
      occurs with almost twice larger barrier for the "naked" cluster compared to the
      adsorbed species, 30.7 versus 15.9 kcal/mol. Furthermore, this reaction step is
      endothermic (by 11.4 kcal/mol) for the gas-phase cluster but exothermic by 7.8
      kcal/mol for the adsorbed cluster. Dissociation of the formed hydrazine molecule
      from the on-surface complex X/MgO and the "naked" complex X requires 19.1 and
      26.3 kcal/mol, respectively. Thus, the Zr(2)Pd(2) adsorption on the MgO(100)
      surface facilitates its reaction with N(2) and four H(2) molecules, as well as
      formation of hydrazine from the hydrogen and nitrogen molecules. The reported
      differences in the reactivity of the "naked" and MgO adsorbed Zr(2)Pd(2) clusters
      were explained by analyzing the nature of the H(2) addition steps in these
      systems.

PMID- 20128600
TI  - Ternary rare-earth iron arsenides RE12Fe57.5As41 (RE = La, Ce).
AB  - The rare-earth iron arsenides RE(12)Fe(57.5)As(41) (RE = La, Ce) have been
      prepared by direct reactions of the elements in the presence of a Sn flux.
      Analysis of single-crystal X-ray diffraction data reveals that they adopt a new
      orthorhombic structure type (Pearson symbol oP236, space group Pmmn, Z = 2; a =
      10.8881(9) A, b = 25.753(2) A, c = 12.5436(10) A for RE = La; a = 10.8376(8) A, b
      = 25.639(2) A, c = 12.4701(9) A for RE = Ce). In this metal-rich arsenide, the
      complex three-dimensional network (derived from 4 RE, 24 Fe, and 17 As sites) can
      be described as being built from unusual wavelike layers of connected As-centered
      trigonal prisms. Five of the Fe sites are partially occupied. The electronic
      structure of these compounds was probed through core-line X-ray photoelectron
      spectra. Magnetic susceptibility measurements indicated ferromagnetic ordering at
      T(C) = 125 and 95 K for the La and Ce compounds, respectively. Electrical
      resistivity measurements on single crystals of Ce(12)Fe(57.5)As(41) showed
      metallic behavior with a prominent transition that coincides closely with the
      ferromagnetic ordering temperature.

PMID- 20128601
TI  - Graphene analogues of BN: novel synthesis and properties.
AB  - Enthused by the fascinating properties of graphene, we have prepared graphene
      analogues of BN by a chemical method with a control on the number of layers. The
      method involves the reaction of boric acid with urea, wherein the relative
      proportions of the two have been varied over a wide range. Synthesis with a high
      proportion of urea yields a product with a majority of 1-4 layers. The surface
      area of BN increases progressively with the decreasing number of layers, and the
      high surface area BN exhibits high CO(2) adsorption, but negligible H(2)
      adsorption. Few-layer BN has been solubilized by interaction with Lewis bases. We
      have used first-principles simulations to determine structure, phonon dispersion,
      and elastic properties of BN with planar honeycomb lattice-based n-layer forms.
      We find that the mechanical stability of BN with respect to out-of-plane
      deformation is quite different from that of graphene, as evident in the
      dispersion of their flexural modes. BN is softer than graphene and exhibits
      signatures of long-range ionic interactions in its optical phonons. Finally,
      structures with different stacking sequences of BN have comparable energies,
      suggesting relative abundance of slip faults, stacking faults, and structural
      inhomogeneities in multilayer BN.

PMID- 20128602
TI  - New benzophenone-derived bisphosphonium salts as leishmanicidal leads targeting
      mitochondria through inhibition of respiratory complex II.
AB  - A set of benzophenone-derived bisphosphonium salts was synthesized and assayed
      for lethal activity on the human protozoan parasite Leishmania. A subset of them,
      mostly characterized by phosphonium substituents with an intermediate
      hydrophobicity, inhibited parasite proliferation at low micromolar range of
      concentrations. The best of this subset, 4,4'-bis((tri-n
      pentylphosphonium)methyl)benzophenone dibromide, showed a very scarce toxicity on
      mammalian cells. This compound targets complex II of the respiratory chain of the
      parasite, based on (i) a dramatically swollen mitochondrion in treated parasites,
      (ii) fast decrease of cytoplasmic ATP, (iii) a decrease of the electrochemical
      mitochondrial potential, and (iv) inhibition of the oxygen consumption rate using
      succinate as substrate. Thus, this type of compounds represents a new lead in the
      development of leishmanicidal drugs.

PMID- 20128603
TI  - Structure of human G protein-coupled receptor kinase 2 in complex with the kinase
      inhibitor balanol.
AB  - G protein-coupled receptor kinase 2 (GRK2) is a pharmaceutical target for the
      treatment of cardiovascular diseases such as congestive heart failure, myocardial
      infarction, and hypertension. To better understand how nanomolar inhibition and
      selectivity for GRK2 might be achieved, we have determined crystal structures of
      human GRK2 in complex with Gbetagamma in the presence and absence of the AGC
      kinase inhibitor balanol. The selectivity of balanol among human GRKs is
      assessed.

PMID- 20128604
TI  - Xenobiotic metabolism and berry flavonoid transport across the blood-brain
      barrier.
AB  - A compelling body of literature suggests berry phytochemicals play beneficial
      roles in reversing age-related cognitive impairment and protect against
      neurodegenerative disorders. Anthocyanins are bioactive phytochemicals in berries
      suspected to be responsible for some of these neuroprotective effects. The
      plausible mechanisms of anthocyanin bioactivity in brain tissue are dependent on
      their bioavailability to the brain. Pigs were fed 2% whole freeze-dried, powdered
      blueberry in the diet for 8 weeks. Anthocyanin and anthocyanin glucuronides were
      measured in the cortex, cerebellum, and midbrain and diencephalon by LC-MS/MS.
      Anthocyanins and their glucuronides were found in the range of femtomoles per
      gram of fresh weight of tissue at 18 h postprandial, after anthocyanins had been
      removed from the blood by xenobiotic metabolism. Xenobiotic metabolism,
      anthocyanin interaction, and transporter barriers to brain bioavailability are
      briefly discussed. The plausible mechanism of neuroprotective action of
      anthocyanins may be via modulation of signal transduction processes and/or gene
      expression in brain tissue rather than by direct antioxidant radical quenching.

PMID- 20128605
TI  - Carbohydrate moieties contribute significantly to the physicochemical properties
      of french bean 7s globulin phaseolin.
AB  - We have previously reported that the solubility of French bean 7S globulin
      (phaseolin) at low ionic strength and its emulsifying stability are remarkably
      high compared with those of 7S globulins prepared from other plant species,
      including soybean (Kimura et al. J. Agric. Food Chem. 2008, 56, 10273-10279). In
      this study, we examined the role of carbohydrate moieties in the properties of
      phaseolin. Three preparations of phaseolin were analyzed: (i) N7S, prepared from
      defatted seed meal and having intact carbohydrate moieties; (ii) R7S, expressed
      in E. coli and lacking N-linked glycans; and (iii) EN7S, having partial N-linked
      glycans after treatment with Endo H. The solubilities of N7S and EN7S were much
      higher than that of R7S at a low ionic strength (micro = 0.08). N7S exhibited
      good emulsifying ability under the conditions examined, but R7S did not. In terms
      of emulsion stability, an emulsion of R7S separated into two phases after 1 h at
      micro = 0.01, 0.08, and 0.5, whereas the emulsion of N7S was stable for 5 days at
      micro = 0.01 and for at least 10 days at micro = 0.08 and 0.5. The emulsion
      stability of EN7S was comparable to that of N7S under most conditions examined.
      These results indicate the carbohydrate modifications are necessary for the good
      solubility, emulsifying ability, and emulsion stability of phaseolin. Further, a
      structural analysis of the carbohydrate moieties indicates that truncated
      carbohydrate moieties are sufficient for conferring these physicochemical
      properties to phaseolin.

PMID- 20128606
TI  - Synthesis, structural analysis, and reactivity of bridged orthoamides by
      intramolecular Schmidt reaction.
AB  - Intramolecular Schmidt reactions can be reliably steered toward bridged
      heterocycles containing orthoamides in high yields. The ketal tether enhances the
      control of regioselectivity in the migration of the bond distal to the reactive
      azide nucleophile, thus providing the first examples of the intramolecular
      Schmidt reaction proceeding with a complete regioselectivity en route to bridged
      products. The method is broad in scope and allows for systematic study of
      compounds that are analogous to elusive tetrahedral intermediates of amide
      addition reactions. Some initial reactivity and structural profiling of these
      compounds are also reported.

PMID- 20128607
TI  - Selective growth of monoclinic and tetragonal zirconia nanocrystals.
AB  - The growth of metal oxide nanocrystals with a well-organized crystalline phase is
      of fundamental and technological interest because in this way it is possible to
      tune their size-dependent unique properties. In this communication, we
      demonstrate the selective growth of monoclinic and tetragonal ZrO(2) nanocrystals
      of <10 nm diameter driven by controlling the surface energy, with and without
      capping by N(CH(3))(4)(+). The nanocrystals were grown in aqueous solution at 150
      degrees C. It was revealed, by transmission electron microscopy, X-ray
      diffraction, Raman spectroscopy, and optical absorption studies, that the
      nanocrystals capped by N(CH(3))(4)(+) have a less defective pure monoclinic
      phase, while those without capping have a pure tetragonal phase with highly
      disordered oxygen vacancies. The N(CH(3))(4)(+) capping on the surface oxygen
      site can reduce the surface energy low enough to stabilize the monoclinic phase.
      By contrast, the bare surface oxygen site has higher energy; thereby, the lower
      surface energy tetragonal phase is formed spontaneously. The present concept is a
      promising universal approach to control the crystal phases of technologically
      important oxide nanocrystals.

PMID- 20128608
TI  - Reactivity of an aryl-substituted silicon-silicon triple bond: reactions of a 1,2
      diaryldisilyne with alkenes.
AB  - The reactivity of a bulky, diaryl-substituted disilyne, Ar-Si identical withSi
      Ar, was examined for the first time. Reaction of the disilyne with ethylene
      yielded an ethylene-bridged bis(silacyclopropane), which is interpreted as a
      further reaction product of the initially formed 1,2-disilacyclobutene species
      with ethylene. A cyclohexane fused with a 1,2-disilacyclobutene was obtained in
      the reaction with cyclohexene. In the reaction with 2,3-dimethyl-1,3-butadiene, a
      tricyclo derivative was isolated from the complex product mixture.

PMID- 20128609
TI  - Epitaxy of Ge nanowires grown from biotemplated Au nanoparticle catalysts.
AB  - Semiconductor nanowires (NWs) are being actively investigated due to their unique
      functional properties which result from their quasi-one-dimensional structure.
      However, control over the crystallographic growth direction, diameter, location,
      and morphology of high-density NWs is essential to achieve the desirable
      properties and to integrate these NWs into miniaturized devices. This article
      presents evidence for the suitability of a biological templated catalyst approach
      to achieve high-density, epitaxial growth of NWs via the vapor-liquid-solid (VLS)
      mechanism. Bacterial surface-layer protein lattices from Deinococcus radiodurans
      were adsorbed onto germanium substrates of (111), (110), and (100)
      crystallographic orientations and used to template gold nanoparticles (AuNPs) of
      different diameters. Orientation-controlled growth of GeNWs was achieved from
      very small size (5-20 nm) biotemplated AuNP catalysts on all of the substrates
      studied. Biotemplated GeNWs exhibited improved morphologies, higher densities
      (NW/microm(2)), and more uniform length as compared to GeNWs grown from
      nontemplated AuNPs on the substrate surfaces. The results offer an integrated
      overview of the interplay of parameters such as catalyst size, catalyst density,
      substrate crystallographic orientation, and the presence of the protein template
      in determining the morphology and growth direction of GeNWs. A comparison between
      templated and nontemplated growth provides additional insight into the mechanism
      of VLS growth of biotemplated NWs.

PMID- 20128610
TI  - Drude relaxation rate in grained gold nanoantennas.
AB  - The effect of grain boundaries on the electron relaxation rate is significant
      even for large area noble metal films and more so for plasmonic nanostructures.
      Optical spectroscopy and X-ray diffraction show a substantial improvement in
      plasmon resonance quality for square-particle nanoantennas after annealing due to
      an enlarged grain size from 22 to 40 nm and improved grain boundaries described
      by the electron reflection coefficient. The electron relaxation rate due to the
      grains is shown to decrease by a factor of 3.2.

PMID- 20128611
TI  - Mechanism and regioselectivity of the osmium-catalyzed aminohydroxylation of
      olefins.
AB  - The mechanism and regioselectivity of the osmium-catalyzed aminohydroxylation of
      olefins was investigated in detail by density functional theory (B3LYP/6-31G(d))
      calculations in the gas phase and with the CPCM-solvent model. A systematic
      variation of the catalyst system (OsO(4) and various nitrogen sources) and the
      substrate's electronic situation was conducted. Activation barriers could be
      correlated to Hammett values and linear Gibbs free energy relations could be
      determined. Experimental results, which indicated an electronic influence on the
      regioselectivity, could be confirmed and appear to be predictable. The reaction
      follows a [3+2] mechanism. We additionally report results on the experimentally
      observed competing dihydroxylation reaction and the ligand-induced reaction rate
      acceleration.

PMID- 20128612
TI  - Targeted dendrimeric anticancer prodrug: a methotrexate-folic acid
      poly(amidoamine) conjugate and a novel, rapid, "one pot" synthetic approach.
AB  - A targeted dendrimeric anticancer prodrug, a conjugate of generation 5 (G5)
      polyamidoamine (PAMAM) dendrimer, folic acid (FA), and methotrexate (MTX), has
      been successfully synthesized by using a novel "one pot" approach which is
      simple, reproducible, and feasible for large-scale synthesis. All dendrimer
      products have been characterized by (1)H NMR, MALDI-TOF, GPC, and HPLC. With this
      new method, the ratio of FA versus MTX attached to the dendrimer can be easily
      tuned to achieve the desired therapeutic effect. A new analytical approach for
      calculating the numbers of FA and MTX attached to the dendrimer has been
      established. In vitro studies performed on FA receptor-expressing KB cells show
      that the new conjugate has a similar affinity and cytotoxic potency to G5-FA-MTX
      synthesized using the traditional multiple-step approach. 

PMID- 20128613
TI  - Self-assembly and dual-stimuli sensitivities of hydroxypropylcellulose-graft
      poly(N,N-dimethyl aminoethyl methacrylate) copolymers in aqueous solution.
AB  - The self-assembly and pH- and thermo-sensitivities properties of hydroxypropyl
      cellulose-graft-poly(N,N-dimethyl aminoethyl methacrylate) (HPC-g-PDMAEMA)
      copolymers in aqueous solutions were investigated by transmittance, dynamic light
      scattering (DLS), and (1)H NMR spectroscopy. Micelles with different structure
      can be formed by varying either pH value or temperature. At low pH, e.g., 3.0,
      the HPC backbone of the copolymer collapse to form the core of micelles
      stabilized with protonated PDMAEMA side chains on the surface of the micelles
      upon heating. At the medium pH, e.g., 8.1, both HPC backbone and PDMAEMA side
      chains collapse upon heating to form unstable aggregates. At high pH, e.g., 12.3,
      PDMAEMA side chains collapse first to form the core of micelles stabilized with
      HPC chains upon heating. Further heating the copolymer solution at this pH leads
      to the aggregation of the micelles due to the collapse of the shell HPC chains.
      The thermal sensitivity of the HPC-g-PDMAEMA copolymers is reversible.

PMID- 20128614
TI  - Science in the art of the master Bizen potter.
AB  - Bizen stoneware, with the characteristic reddish hidasuki or "fire-marked"
      pattern, is one of Japan's best known traditional ceramic works of art. The means
      of creating and controlling the various hues of the hidasuki pattern has remained
      a mystery to outsiders for about a thousand years; the methods were known only to
      master potters who served under generations of master potters before them. In
      this Account, we present the results of 30 years of study in which we
      investigated the microstructure and color-formation process in Bizen stoneware.
      We discovered that the hidasuki pattern results from the precipitation of
      corundum (alpha-Al(2)O(3)) and the subsequent epitaxial growth of hematite (alpha
      Fe(2)O(3)) around it in a approximately 50-microm-thick liquid specifically
      formed in the ceramic surface. The epitaxial composites include hexagonal plate
      like alpha-Fe(2)O(3)/alpha-Al(2)O(3)/alpha-Fe(2)O(3) sandwiched particles and
      also surprisingly beautiful flower-like crystals, centered by hexagonal corundum
      crystals and decorated by several hexagonal hematite petal crystals. Bizen
      stoneware is produced from a unique clay that can only be mined from the Bizen
      area of Okayama Prefecture, Japan. The clay has an unusually high Fe content
      compared with the traditional porcelain clay, as well as Si, Ca, Mg, and Na.
      Prior to firing, the Bizen works are wrapped in rice straw that was used
      originally as a separator to prevent adhesion. The hidasuki pattern only appears
      where the rice straw is in direct contact with the clay; the rice straw supplies
      potassium, which reduces the melting point of the ceramic surface, thereby
      converting the contact area into a site for these reactions to take place. The
      effect is almost accidental and is produced without the aid of any artificial
      glazing and enameling. An unexpected variety of substances, including metallic
      iron coated by graphite, Fe(3)P, and epsilon-Fe(2)O(3), were also found to appear
      at low oxygen partial pressures. Many of the techniques used by master potters
      are passed down through an apprenticeship system; an unfortunate consequence is
      that they are poorly documented. Moreover, the masters of these techniques are
      often unaware of the underlying chemical reactions that take place. Chemical
      studies of traditional processes can provide new inspiration to artists, allowing
      them to control the various factors and thus produce new works, and perhaps new
      functional materials. We studied the process of creating Bizen stoneware and then
      mimicked the color-producing process under controlled laboratory conditions,
      demonstrating the possibilities of the endeavor.

PMID- 20128615
TI  - Statistical indices for simultaneous large-scale metabolite detections for a
      single NMR spectrum.
AB  - NMR-based metabolomics has become a practical and analytical methodology for
      discovering novel genes, biomarkers, metabolic phenotypes, and dynamic cell
      behaviors in organisms. Recent developments in NMR-based metabolomics, however,
      have not concentrated on improvements of comprehensiveness in terms of
      simultaneous large-scale metabolite detections. To resolve this, we have devised
      and implemented a statistical index, the SpinAssign p-value, in NMR-based
      metabolomics for large-scale metabolite annotation and publicized this
      information. It enables simultaneous annotation of more than 200 candidate
      metabolites from the single (13)C-HSQC (heteronuclear single quantum coherence)
      NMR spectrum of a single sample of cell extract.

PMID- 20128616
TI  - Desorption electrospray ionization mass spectrometry analysis of lipids after two
      dimensional high-performance thin-layer chromatography partial separation.
AB  - Molecular imaging of separate but still incompletely resolved spots on high
      performance thin-layer chromatography (HPTLC) plates is used for the direct
      analysis of porcine brain lipids by desorption electrospray ionization mass
      spectrometry (DESI-MS). Eight class-specific spots were imaged in the negative
      ion mode and shown to contain more than fifty lipids. A low lateral resolution of
      400 x 400 microm allowed simple, rapid, and incomplete separation to be combined
      with DESI imaging for the identification of many components of these extremely
      complex mixtures. In this work, tandem mass spectrometry (MS/MS) was also
      employed to confirm the identity of particular lipids directly on HPTLC plates.

PMID- 20128617
TI  - Multiclass, multiresidue drug analysis, including aminoglycosides, in animal
      tissue using liquid chromatography coupled to tandem mass spectrometry.
AB  - A multiresidue, multiclass semiquantitative screening analysis of 39 drug
      residues covering 8 drug classes, including aminoglycosides in veal muscle, based
      on a single multiresidue extraction routine and using high-performance liquid
      chromatography coupled to electrospray ionization tandem mass spectrometry (LC
      ESI-MS/MS), is presented. Sample preparation involves extraction of a 5 g diced
      tissue sample with 10 mL of acetonitrile/ water (86:14), incubated at 60 degrees
      C for 1 h, and then cooled for 10 min in ice. Formic acid is added to the
      suspension, then mixed, and centrifuged. The supernatant is retained, and the
      pellet is extracted with 10 mL of water for aminoglycosides and again
      centrifuged. Approximately 9.5 mL of each of the supernatants from both extracts
      is combined and diluted with water to 25 mL. The final solution is then defatted
      with 20 mL of hexane prior to analysis. Liquid chromatography for the
      aminoglycosides is carried out with ZIC-HILIC and for the remainder of the
      compounds with an Atlantis dC18 minicolumn. LC-ESI-MS/MS in positive and negative
      ionization modes (three injections total) is carried out, and two ion transitions
      per analyte are monitored. The method provides semiquantitative analysis to
      identify incurred positive drug classes in a rapid and cost-effective manner. Of
      particular interest is the detection of numerous compounds in the low nanograms
      per gram concentration range, which are not typically detected using receptor
      based screening methods. All identified drugs were confirmed using
      internationally recognized regulatory methods, with no apparent false positives.

PMID- 20128618
TI  - Cyclic biamperometry.
AB  - Cyclic biamperometry has been investigated as a method for the quantitation of
      one form of a reversibly electroactive redox couple in the presence of the other
      form, using the ferri-ferrocyanide couple in aqueous KCl. A triangular voltage
      waveform applied across two equal-area, planar gold electrodes yields peak
      currents that depend on the square root of the applied voltage scan rate, when
      one form of the redox couple is present in excess. Independent measurement of
      electrode-to-solution potential during biamperometric scans allowed estimation of
      the fractional impedance at each electrode-solution interface, and these values
      allow calculation of the effective potential scan rates at each electrode.
      Results show that when one form is present in a 5-fold excess or greater, the
      potential scan rate for the limiting reaction is nearly identical to the applied
      voltage scan rate. Similar values were obtained from impedance calculations, but
      discrepancies between the predicted and experimental values are evident when the
      two forms are present at near equivalent concentrations. When one form of the
      redox couple is present in excess, cyclic biamperometric peak currents depend
      linearly on the concentration of the limiting form, and these currents can be
      amplified by using cells with one electrode much larger than the other. Because
      this method does not require a reference electrode, it can, in principle, be
      readily incorporated into new electrochemical array or lab-on-a-chip devices.

PMID- 20128619
TI  - Asymmetric synthesis of a potent, aminopiperidine-fused imidazopyridine
      dipeptidyl peptidase IV inhibitor.
AB  - A practical asymmetric synthesis of a novel aminopiperidine-fused imidazopyridine
      dipeptidyl peptidase IV (DPP-4) inhibitor 1 has been developed. Application of a
      unique three-component cascade coupling with chiral nitro diester 7, which is
      easily accessed via a highly enantioselective Michael addition of dimethyl
      malonate to a nitrostyrene, allows for the assembly of the functionalized
      piperidinone skeleton in one pot. Through a base-catalyzed, dynamic
      crystallization-driven process, the cis-piperidionone 16a is epimerized to the
      desired trans isomer 16b, which is directly crystallized from the crude reaction
      stream in high yield and purity. Isomerization of the allylamide 16b in the
      presence of RhCl(3) is achieved without any epimerization of the acid/base labile
      stereogenic center adjacent to the nitro group on the piperidinone ring, while
      the undesired enamine intermediate is consumed to <0.5% by utilizing a trace
      amount of HCl generated from RhCl(3). The amino lactam 4, obtained through
      hydrogenation and hydrolysis, is isolated as its crystalline pTSA salt from the
      reaction solution directly, as such intramolecular transamidation has been
      dramatically suppressed via kinetic control. Finally, a Cu(I) catalyzed coupling
      cyclization allows for the formation of the tricyclic structure of the potent DPP
      4 inhibitor 1. The synthesis, which is suitable for large scale preparation, is
      accomplished in 23% overall yield.

PMID- 20128620
TI  - Exploring photoinduced decarboxylation mechanism of o-acetylphenylacetic acid
      from the combined CASSCF and DFT studies.
AB  - In the present work, we studied the near-UV photoinduced decarboxylation of o
      acetylphenylacetic acid with complete active space self-consistent field and
      density functional theory. It was found that irradiation at approximately 300 nm
      results in o-acetylphenylacetic acid in the S(1)((1)npi*) state, which is
      followed by a rapid relaxation and efficient intersystem crossing to the
      T(1)((3)npi*) state via the S(1)/T(2)/T(1) three-surface intersection. The 1,5-H
      shift has a barrier of 1.9 kcal x mol(-1) on the T(1) pathway to the triplet 1,4
      biradical, which is in good agreement with a rate constant of about 10(10) s(-1)
      inferred experimentally for o-alkylphenyl ketones. The subsequent reactions occur
      with little probability from the triplet 1,4-biradical, due to relatively high
      barrier or high endothermicity for the spin-conservation triplet pathways. As a
      result, intersystem crossing to the lowest singlet state takes place prior to the
      subsequent reactions. Four isomers, (3)BRi (i = 1-4), were found to be stable for
      the triplet 1,4-biradical. The calculated energy gap indicates that the
      (3)BR3/(3)BR2 ratio is close to 1:1, and populations of (3)BR1 and (3)BR4 are
      less than 1% at thermal equilibrium. Like the triplet 1,4-biradical, four stable
      isomers of (1)Xi (i = 1-4) were determined in the lowest singlet state. Because
      of the relatively high barrier (approximately 30 kcal x mol(-1)) on the
      isomerization pathways, the thermal equilibrium is not established among the four
      singlet isomers, which is different from the situation for the triplet 1,4
      biradical. In this case, the subsequent reactions proceed mainly from the (1)X2
      and (1)X3 isomers that correspond to (3)BR2 and (3)BR3. There is only one
      predominant pathway from the (1)X2 isomer, namely, the reversed-H shift to the
      initial reactant of o-acetylphenylacetic acid. However, several possible pathways
      exist for the (1)X3 deactivation: intramolecular cyclization, unimolecular
      decarboxylation, and the parent acid-catalyzed bimolecular decarboxylation. The
      unimolecular decarboxylation is not in competition with the cyclization. But the
      cyclization reaction is prevented by the parent acid-catalyzed bimolecular
      decarboxylation, which is responsible for the products of CO(2) and o-acyltoluene
      observed experimentally. The (1)X3/(1)X2 ratio is nearly equal to that for
      (3)BR3/(3)BR2, which indicates that the decarboxylation reaction has a quantum
      yield close to 0.5. The o-acyltoluene product was isolated, and its yield was
      experimentally estimated to be in the 50% range.

PMID- 20128621
TI  - Approaches to increasing surface stress for improving signal-to-noise ratio of
      microcantilever sensors.
AB  - Microcantilever sensor technology has been steadily growing for the last 15
      years. While we have gained a great amount of knowledge in microcantilever
      bending due to surface stress changes, which is a unique property of
      microcantilever sensors, we are still in the early stages of understanding the
      fundamental surface chemistries of surface-stress-based microcantilever sensors.
      In general, increasing surface stress, which is caused by interactions on the
      microcantilever surfaces, would improve the S/N ratio and subsequently the
      sensitivity and reliability of microcantilever sensors. In this review, we will
      summarize (A) the conditions under which a large surface stress can readily be
      attained and (B) the strategies to increase surface stress in case a large
      surface stress cannot readily be reached. We will also discuss our perspectives
      on microcantilever sensors based on surface stress changes.

PMID- 20128622
TI  - Programmable nano-bio-chip sensors: analytical meets clinical.
AB  - There have been many recent advances in the nano-bio-chip analysis methodology
      with implications for a number of high-morbidity diseases including HIV, cancer,
      and heart disease. (To listen to a podcast about this article, please go to the
      Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html
      .).

PMID- 20128623
TI  - Locally functionalized short-range ordered nanoplasmonic pores for bioanalytical
      sensing.
AB  - Nanoplasmonic sensors based on short-range ordered nanoholes in thin metal films
      and discrete metal nanoparticles are known to provide similar sensing
      performance. However, a perforated metal film is unique in the sense that the
      holes can be designed to penetrate through the substrate, thereby also fulfilling
      the role of nanofluidic channels. This paper presents a bioanalytical sensing
      concept based on short-range ordered nanoplasmonic pores (diameter 150 nm)
      penetrating through a thin (around 250 nm) multilayer membrane composed of gold
      and silicon nitride (SiN) that is supported on a Si wafer. Also, a fabrication
      scheme that enables parallel production of multiple (more than 50) separate
      sensor chips or more than 1000 separate nanoplasmonic membranes on a single wafer
      is presented. Together with the localization of the sensitivity to within such
      short-range ordered nanoholes, the structure provides a two-dimensional
      nanofluidic network, sized in the order of 100 x 100 microm(2), with nanoplasmon
      active regions localized to each individual nanochannel. A material-specific
      surface-modification scheme was developed to promote specific binding of target
      molecules on the optically active gold regions only, while suppressing
      nonspecific adsorption on SiN. Using this protocol, and by monitoring the
      temporal variation in the plasmon resonance of the structure, we demonstrate flow
      through nanoplasmonic sensing of specific biorecognition reactions with a signal
      to-noise ratio of around 50 at a temporal resolution below 190 ms. With flow, the
      uptake was demonstrated to be at least 1 order of magnitude faster than under
      stagnant conditions, while still keeping the sample consumption at a minimum.

PMID- 20128624
TI  - Synthesis of biotinylated alpha-D-mannoside or N-acetyl beta-D-glucosaminoside
      decorated gold nanoparticles: study of their biomolecular recognition with Con A
      and WGA Lectins.
AB  - Gold nanoparticles (NPs) functionalized with a mixed shell of well-defined
      biotinylated glycopolymers and polyethylene glycol (PEG) provide an effective
      platform for the biomolecular recognition of proteins both in solution and on
      surfaces. Well-defined biotinylated glycopolymers were first synthesized by the
      reversible addition-fragmentation chain transfer (RAFT) process. They contain two
      types of carbohydrate residues either N-acetyl beta-D-glucosaminopyranoside
      (GlcNAc) or alpha-D-mannopyranoside (Man) as pendent groups. The biotinylated
      glycopolymers and polyethylene glycol were subsequently used in the in situ
      formation of gold glyconanoparticles via an easy photochemical process. The
      obtained biotinylated glyconanoparticles were characterized by dynamic light
      scattering (DLS) and transmission electron microscopy (TEM). The bioavailability
      of the biotin and specific carbohydrate residues at the periphery of the NPs were
      assessed using the diffraction optic technology (DOT) system. The studies showed
      the accessibility of the biotin ligands for conjugation to immobilized avidin on
      the DOTLab biosensor. Furthermore, these avidin conjugated glyconanoparticles
      were found to selectively immobilize lectins. The specificity of lectin binding
      was dependent on the type of carbohydrate residues. As such, N-acetyl beta-D
      glucosaminoside decorated gold nanoparticles were found to specifically interact
      with wheat germ agglutinin (WGA) lectin, whereas alpha-D-mannoside ones were
      found to specifically interact with Concanavalin A (Con A) lectin.

PMID- 20128625
TI  - Total synthesis of (+)-crocacin C using hidden symmetry.
AB  - A highly convergent and protecting-group-free synthesis of (+)-crocacin C,
      featuring an enzymatic enantioselective desymmetrization of a meso-diol, a base
      induced ring opening of a THP ring, and a one-pot hydrostannylation/Stille
      coupling as the key steps, is reported. The natural product was obtained in 11
      steps and 22.3% overall yield starting from readily available oxabicycle 1.
      Finally, a unique enantioselective step, an enzymatic desymmetrization, revealed
      four stereogenic centers and created one in C4 of the THP furnishing the dense
      building block 4 with high enantioselectivity (ee >98%).

PMID- 20128626
TI  - Effect of calcium-sensitizing mutations on calcium binding and exchange with
      troponin C in increasingly complex biochemical systems.
AB  - The calcium-dependent interactions between troponin C (TnC) and other thin and
      thick filament proteins play a key role in the regulation of cardiac muscle
      contraction. Five hydrophobic residues (Phe(20), Val(44), Met(45), Leu(48), and
      Met(81)) in the regulatory domain of TnC were individually substituted with polar
      Gln, to examine the effect of these mutations that sensitized isolated TnC to
      calcium on (1) the calcium binding and exchange with TnC in increasingly complex
      biochemical systems and (2) the calcium sensitivity of actomyosin ATPase. The
      hydrophobic residue mutations drastically affected calcium binding and exchange
      with TnC in increasingly complex biochemical systems, indicating that side chain
      intra- and intermolecular interactions of these residues play a crucial role in
      determining how TnC responds to calcium. However, the mutations that sensitized
      isolated TnC to calcium did not necessarily increase the calcium sensitivity of
      the troponin (Tn) complex or reconstituted thin filaments with or without myosin
      S1. Furthermore, the calcium sensitivity of reconstituted thin filaments (in the
      absence of myosin S1) was a better predictor of the calcium dependence of
      actomyosin ATPase activity than that of TnC or the Tn complex. Thus, both the
      intrinsic properties of TnC and its interactions with the other contractile
      proteins play a crucial role in modulating the binding of calcium to TnC in
      increasingly complex biochemical systems.

PMID- 20128627
TI  - Proteomic analysis of the Enterococcus faecalis V583 strain and clinical isolate
      V309 under vancomycin treatment.
AB  - To understand the molecular mechanisms of bacteria resistance to glycopeptides,
      we obtained proteomic profiles of vancomycin-resistant Enterococcus faecalis V583
      (reference strain) and V309 (clinical isolate) passaged with and without the
      drug. The specificity and reversibility of vancomycin resistance genes induced in
      V583 and V309 were further studied over time. By semiquantitative RT-PCR of
      vancomycin-treated versus untreated samples of both strains, 28 (V583) or 20
      (V309) up-regulated proteins, 8 (V583) or 6 (V309) down-regulated proteins, and 1
      (V583) or 4 (V309) proteins with mobility changes in 2-DE gel analysis were
      identified. Some of these proteins have known vancomycin resistance functions or
      are related to virulent factors, stress, metabolism, translation, and
      conjunction, which would help Enterococcus survive under drug selection.
      Vancomycin induced specifically and reversibly VanA, VanX, VanB, and VanXB.
      Notably, 6 proteins (Pgm, Ldh, Gap-2, RpsB, EF2076, and sex pheromone cAD1
      precursor lipoprotein) exhibited clear post-translational modifications.
      Vancomycin induced phosphorylation of Ser/Thr in Ldh, Gap-2, and sex pheromone
      cAD1 precursor lipoprotein (EF3256), newly identified here as enterococcal
      phosphoproteins. Our data suggest that phosphorylated EF3256 is normally active
      in E. faecelis, whereas EF3256-P together with oppA-like protein may play a key
      role in the regulation of pheromone and transmission of conjugation plasmids.

PMID- 20128628
TI  - Formulation and delivery of splice-correction antisense oligonucleotides by amino
      acid modified polyethylenimine.
AB  - Splice-correcting phosphorothioate RNA antisense oligonucleotides with 2'-O
      methyl modifications (ASO) are promising therapeutic agents for several disorders
      caused by aberrant splicing. However, their usefulness is hindered by the lack of
      efficient delivery. Unmodified 25 kDa polyethylenimine (PEI) has shown potential
      for plasmid delivery but seems to be less efficient for short nucleic acid
      sequences. Herein, we have evaluated several amino acid modified PEI molecules as
      carriers for ASO. By characterization of their properties, such as size,
      stability and transfection into mammalian cells, we have identified tyrosine
      modified PEI (PEIY) as an efficient ASO delivery system. HeLa705 cells containing
      an aberrant luciferase gene, interrupted by a mutated beta-globin intron, were
      used to assess the splice correction effectiveness mediated by the various
      modified PEI/ASO polyplexes. PEIY has a self-assembly nature, as opposed to the
      highly cationic parent polymer, which is relevant for the stability of the
      PEIY/ASO complexes. As a result, at an optimal ratio of 20:1 (+/-), the complexes
      that formed significantly corrected the splicing on both the mRNA and the protein
      levels. ASO formulated with PEIY enhanced luciferase activity up to 450-fold.
      This increase was three times higher than that produced by the commercially
      available transfection agent Lipofectamine. PEIY/ASO polyplexes resulted in at
      least 80% correct splicing of the transcript. Moreover, extremely low doses of
      ASO (0.025 microM) showed significant splice correction represented by 150-fold
      increase of luciferase activity and 47% mRNA correction. Our findings suggest key
      parameters for formulating active complexes and reveal a new platform that can be
      further developed for ASO in vivo targeting.

PMID- 20128629
TI  - Transient optical studies of interfacial charge transfer at nanostructured metal
      oxide/PbS quantum dot/organic hole conductor heterojunctions.
AB  - We report a transient absorption and luminescence study addressing the charge
      separation, recombination, and regeneration reactions at nanostructured metal
      oxide/PbS quantum dot/organic hole conductor heterojunctions. We show that yields
      of charge separation are significantly higher at PbS/SnO(2) interfaces relative
      to PbS/TiO(2) interfaces, and conclude that this behavior is a result of the ca.
      300-500 meV lower conduction band edge in SnO(2) as compared to TiO(2). We also
      report a correlation between the PbS particle size and the yield of charge
      separation at PbS/SnO(2) interfaces, with a smaller PbS particle radius resulting
      a higher yield of charge separation. Finally we investigated the regeneration of
      the photooxidized PbS by an organic hole transporting material, namely, spiro
      OMeTAD. The overall spiro-OMeTAD(+) yield is found to be 27% at a SnO(2)/PbS
      (approximately 3 nm diameter)/spiro-OMeTAD heterojunction. The addition of a
      lithium salt was found to raise the overall spiro-OMeTAD(+) yield from its
      initial value of 27% (where no Li(+) is present) to 50%. We believe this to be a
      result of an increase in the primary charge injection yield to near unity as the
      SnO(2) conduction band is lowered (with increasing [Li(+)]), increasing the
      driving force for electron injection. The present findings are discussed with
      relevance to the design of PbS-sensitized metal oxide layers for DSSCs.

PMID- 20128630
TI  - Responsiveness and validity of the Motor Activity Log in patients during the
      subacute phase after stroke.
AB  - PURPOSE: To investigate the responsiveness and cross-sectional and longitudinal
      validity of the Motor Activity Log (MAL) in the subacute phase after stroke.
      METHOD: Data were collected pre-intervention, post-intervention, and at 3-month
      follow-up evaluations from 30 patients with stroke participating in a randomized
      trial of forced use. Assessments included MAL, the Fugl-Meyer test, the 16-hole
      peg test, grip strength, the Action Research Arm Test, and the Motor Assessment
      Scale. Measurements of responsiveness were effect size, standardized response
      mean (SRM), and responsiveness ratio (RR). Relationships between the MAL and the
      other measures were determined with Spearman correlations. RESULTS: The MAL is
      responsive to change, with effect size, SRM, and RR>1.0 at the 3-month follow-up,
      and SRM and RR>1.0 at post-intervention. Correlations at the separate test
      occasions between MAL and the other measures were mostly close to 0.50, which
      shows fair to moderate construct validity. Correlations between changes in MAL
      and in the other measures were weaker than cross-sectional relationships.
      CONCLUSIONS: The MAL is a responsive measure of daily hand use in patients
      participating in rehabilitation in the subacute phase after stroke. Correlations
      of construct validity indicate that daily hand use may need to be measured
      separately from body function and activity capacity, in line with the underlying
      constructs of International Classification of Functioning, Disability and Health.
      To strengthen our findings, they should be repeated in larger samples of
      patients.

PMID- 20128631
TI  - A review of the in vivo and in vitro toxicity of silver and gold particulates:
      particle attributes and biological mechanisms responsible for the observed
      toxicity.
AB  - This review is concerned with evaluating the toxicity associated with human
      exposure to silver and gold nanoparticles (NPs), due to the relative abundance of
      toxicity data available for these particles, when compared to other metal
      particulates. This has allowed knowledge on the current understanding of the
      field to be gained, and has demonstrated where gaps in knowledge are. It is
      anticipated that evaluating the hazards associated with silver and gold particles
      will ultimately enable risk assessments to be completed, by combining this
      information with knowledge on the level of human exposure. The quantity of
      available hazard information for metals is greatest for silver particulates, due
      to its widespread inclusion within a number of diverse products (including
      clothes and wound dressings), which primarily arises from its antibacterial
      behaviour. Gold has been used on numerous occasions to assess the biodistribution
      and cellular uptake of NPs following exposure. Inflammatory, oxidative,
      genotoxic, and cytotoxic consequences are associated with silver particulate
      exposure, and are inherently linked. The primary site of gold and silver
      particulate accumulation has been consistently demonstrated to be the liver, and
      it is therefore relevant that a number of in vitro investigations have focused on
      this potential target organ. However, in general there is a lack of in vivo and
      in vitro toxicity information that allows correlations between the findings to be
      made. Instead a focus on the tissue distribution of particles following exposure
      is evident within the available literature, which can be useful in directing
      appropriate in vitro experimentation by revealing potential target sites of
      toxicity. The experimental design has the potential to impact on the
      toxicological observations, and in particular the use of excessively high
      particle concentrations has been observed. As witnessed for other particle types,
      gold and silver particle sizes are influential in dictating the observed
      toxicity, with smaller particles exhibiting a greater response than their larger
      counterparts, and this is likely to be driven by differences in particle surface
      area, when administered at an equal-mass dose. A major obstacle, at present, is
      deciphering whether the responses related to silver nanoparticulate exposure
      derive from their small size, or particle dissolution contributes to the observed
      toxicity. Alternatively, a combination of both may be responsible, as the release
      of ions would be expected to be greater for smaller particles.

PMID- 20128632
TI  - Expression of aberrant beta-catenin and impaired p63 in craniopharyngiomas.
AB  - Craniopharyngiomas are rare, histologically benign, non-neuroepithelial
      epithelial tumors arising from the sellar region, the molecular pathogenesis of
      CPs is yet not understood. The aim of the present study was to assess expression
      of aberrant beta-catenin and impaired p63 in 66 craniopharyngiomas included 51
      adamantinomatous craniopharyngiomas and 15 squamous papillary craniopharyngiomas.
      On immunohistochemistry, 47 out of 51 adamantinomatous craniopharyngiomas, but
      not squamous papillary craniopharyngiomas, showed strong nuclear/cytoplasmic
      expression for beta-catenin predominantly in compactly cohesive epithelial cells
      within the whorl-like arrays where ki-67 was almost absent and rarely in
      palisaded cells where ki-67 was mainly present. P63 overexpression was observed
      in 45 out of 51 adamantinomatous craniopharyngiomas and 14 out of 15 squamous
      papillary craniopharyngiomas. P63 stained not only in the nuclei of basal layer
      cells but also within the whorl-like arrays in adamantinomatous
      craniopharyngiomas and uniformly in squamous papillary craniopharyngiomas. Using
      quantitative real time polymerase chain reaction techniques to correlate p63
      protein expression with p63 mRNA levels, TAp63 isoforms mRNA was reduced, whereas
      DeltaNp63 mRNA elevated at levels in 5 snap frozen tissue samples with multiple
      large p63 positive cell clusters compared with normal tissues. In conclusion, the
      present study confirmed that the two variants of CPs have genetically not only
      distinctive but also common feature. It demonstrated that cytoplasm/nuclear beta
      catenin accumulation is an exclusively characteristic morphology of adaCPs. P63
      immunohistochemical overexpression were found in both adaCPs and spCPs variant
      when analyzed in the same study. Taken together, the impaired p63 expression may
      be attributed to elevated DeltaNp63 mRNA and reduced TAp63mRNA in CPs.

PMID- 20128633
TI  - Peritoneal adhesions in human and veterinary medicine: from pathogenesis to
      therapy. A review.
AB  - Any peritoneal inflammatory process consequent to infections or surgical injuries
      may induce abdominal adhesion formation. Peritoneal adhesions are connective
      laciniae that develop among abdomino-pelvic organs that limit physiologic
      visceral motion. Consequently, fertility may be impaired, and intestinal
      obstruction and pelvic pain may develop, mainly in subjects that had undergone
      gynaecological surgery. This review illustrates the pathogenic steps of
      adhesiogenesis and the therapeutic scenario that evolved over the years to tackle
      the threat of peritoneal adhesions, both in domestic animals and in women.

PMID- 20128634
TI  - High flow extra-cranial to intra-cranial bypass for complex internal carotid
      aneurysms.
AB  - Cerebral revascularisation with extracranial - intracranial (EC-IC) bypass is
      generally indicated in patients with complex anterior circulation aneurysms who
      have failed parent artery occlusion. We report on the process and outcome of our
      early experience of performing high flow bypass in patients with complex anterior
      circulation aneurysms. We have reviewed patients who have undergone an EC-IC
      bypass for treatment of complex anterior circulation aneurysms, and report our
      outcome on graft patency, surgical complications, discharge destination, and
      obliteration rates. Nine patients that underwent 11 bypasses are described. Seven
      patients had a giant saccular aneurysm of the carotid, and these were all
      obliterated on post-operative imaging. Two patients presenting with an
      intracranial carotid dissection required trapping of the diseased segment
      following the bypass. The overall graft patency rate was 88%. One patient
      developed a post operative subdural collection (managed conservatively), and one
      patient required early graft revision. Discharge destination was home in 8/9
      patients. There was no mortality. Although EC-IC bypass is a technically
      challenging procedure, it provides a valuable treatment option for patients with
      complex anterior circulation aneurysms. Good graft patency rates can be achieved
      with low surgical morbidity in patients with a disease process that otherwise
      attracts a highly unfavourable natural history.

PMID- 20128635
TI  - Nutritional and anti-nutritional potential of three accessions of itching bean
      (Mucuna pruriens (L.) DC var. pruriens): an under-utilized tribal pulse.
AB  - Three accessions of the under-utilized legume itching bean (Mucuna pruriens var.
      pruriens) were analysed for proximate composition, mineral profiles, vitamins
      (niacin and ascorbic acid), fatty acid profiles, amino acid profiles of total
      seed protein, in vitro protein digestibility and certain anti-nutritional
      factors. All three accessions of M. pruriens var. pruriens contained higher
      amounts of crude protein and crude lipid when compared with most of the commonly
      consumed pulses. The fatty acid profiles revealed that the seed lipids contained
      a higher concentration of palmitic acid and linoleic acids. Amino acid profiles
      of M. pruriens var. pruriens revealed that the seed protein contained relatively
      higher levels of certain essential amino acids compared with the FAO/WHO
      requirement pattern. The investigated seeds are rich in minerals such as
      potassium, calcium, magnesium, phosphorus, iron and manganese. Anti nutritional
      substances such as total free phenolics, tannins, 3,4-dihydroxyphenylalanine,
      phytic acid, hydrogen cyanide, trypsin inhibitor activity, oligosaccharides and
      phytohaemagglutinating activity were investigated. The anti-nutritional fatty
      acid, behenic acid, also was detected in the present study.

PMID- 20128636
TI  - Total folate: diversity within fruit varieties commonly consumed in India.
AB  - Folate concentrations in selected fruits were measured using the trienzyme
      extraction and microbiological assay with Lactobacillus casei (subsp. Rhamnosus)
      as an assay organism. Fruits were purchased from different retail outlets at
      Coimbatore, Tamilnadu, India and were analyzed for total folate content. The
      folate content in all fruits varied considerably on a fresh weight basis from 10
      to 328 microg/100 g, with tropical fruits ranging between 10 and 211 microg/100
      g, temperate fruits from 11 to 328 microg/100 g, and the subtropical fruits in
      the range of 9-237 microg/100 g. Amongst all fruits, plum had the highest content
      of folate (328 microg/100 g). Data analyzed will assist dietary studies to
      estimate and evaluate the adequacy of folate intakes of the population, to
      formulate experimental diets for folate bioavailability studies, and to revise
      dietary recommendations for the population. In addition, the data will assist the
      health authorities in planning and executing strategies for intervention
      programs.

PMID- 20128637
TI  - Analysis of components and study on antioxidant and antimicrobial activities of
      oil in apple seeds.
AB  - In order to improve the comprehensive utilization of major by-products in apple
      juice processing, the components, antioxidant and antimicrobial activities of oil
      in two species apple seeds, Fuji and New Red Star, were investigated. The Soxhlet
      extracted oil content of apple seeds raged from 20.69 to 24.32 g/100 g. The
      protein, fiber and ash contents were found to be 38.85-49.55 g/100 g, 3.92-4.32
      g/100 g and 4.31-5.20 g/100 g, respectively; the extracted oils exhibited an
      iodine value of 94.14-101.15 g I/100 g oil; refractive index (40 degrees C) was
      1.465-1.466; density (25 degrees C) was 0.902-0.903 mg/ml; saponification value
      was 179.01-197.25 mg KOH/g oil; and the acid value was 4.036-4.323 mg KOH/g oil.
      The apple seed oils mainly consisted of linoleic acid (50.7-51.4 g/100 g) and
      oleic acid (37.49-38.55 g/100 g). Other prominent fatty acids were palmitic acid
      (6.51-6.60 g/100 g), stearic acid (1.75-1.96 g/100 g) and arachidic acid (1.49
      1.54 g/100 g). Apple seed oil was proven to possess interesting properties,
      emerging from its chemical composition and from the evaluation of its in vitro
      biological activities. The apple seed oil was almost completely active against
      bacteria, mildews were less sensitive to apple seed oil than yeasts, and the
      minimum inhibitory concentration (MIC) of apple seed oil ranged from 0.3 to 0.6
      mg/ml. The observed biological activities showed that the oil had a good
      potential for use in the food industry and pharmacy.

PMID- 20128638
TI  - Synthesis, antineoplastic and cytotoxic activities of some mononuclear Ru(II)
      complexes.
AB  - A series of mononuclear Ru(II) complexes of the type [Ru(S)(2)(K)](2+), where S =
      1,10-phenanthroline/2,2'-bipyridine and K = 4-OH-btsz, 4-CH(3)-btsz, 3,4-di
      OCH(3)-btsz, 4-OH-binh, 4-CH(3)-binh, 3,4-di-OCH(3)-binh, were prepared and
      characterized by elemental analysis, FTIR, (1)H-NMR, and mass spectroscopy. The
      complexes displayed metal-ligand charge transfer (MLCT) transitions in the
      visible region. These ligands formed bidentate octahedral ruthenium complexes.
      The title complexes were evaluated for their in vivo anticancer activity against
      a transplantable murine tumor cell line, Ehrlisch's ascites carcinoma (EAC), and
      in vitro cytotoxic activity against human cancer cell lines Molt 4/C(8) and CEM
      and murine tumor cell line L1210. The ruthenium complexes showed promising
      biological activity especially in decreasing tumor volume and viable ascites cell
      counts. Treatment with these complexes prolonged the life span of mice bearing
      EAC tumors by 10-52%. In vitro evaluation of these ruthenium complexes revealed
      cytotoxic activity from 0.21 to 24 muM against Molt 4/C(8), 0.16 to 19 microM
      against CEM, and 0.75 to 32 microM against L1210.

PMID- 20128639
TI  - Editorial 2010 for ocular immunology and inflammation.

PMID- 20128640
TI  - Are the Standardization of the Uveitis Nomenclature (SUN) Working Group criteria
      for codifying the site of inflammation appropriate for all uveitis problems?
      Limitations of the SUN Working Group classification.
AB  - The standardization of Uveitis Nomenclature (SUN) Working Group recently affirmed
      the importance of an anatomic classification of uveitis, endorsing the anatomic
      clasiffication scheme proposed by the International Uveitis Study Group (IUSG).
      The group however pointed out and addressed ambiguities in the IUSG system, and
      proposed new standards for grading the anatomic location and degree of activity
      of inflammation. Besides clarifying some of the existing nomenclature problems
      the terminology proposed by the SUN working group still remains confusing in a
      few points. Ambiguities in the SUN Working group anatomic classification of
      uveitis were addressed, especially regarding the terms "pars planitis",
      "neuroretinitis" and "anterior and intermediate uveitis".

PMID- 20128641
TI  - Controversy: ocular sarcoidosis.
AB  - The recent publication of diagnostic criteria for ocular sarcoidosis has renewed
      interest in this enigmatic and often controversial disease. The aim of the
      present review was to report on the results of a survey of leading
      ophthalmologists in which we asked them to address some of the most important
      issues related to the diagnosis and treatment of ocular sarcoidosis. The survey
      revealed that there is significant uptake and use of the diagnostic criteria for
      ocular sarcoidosis, although there still remained considerable differences in
      opinion with regard to whether or not this was an isolated condition affecting
      only the eye and how this should be diagnosed and appropriately managed.

PMID- 20128642
TI  - Sarcoidosis-associated Unilateral Retinal Arteritis.
AB  - PURPOSE: To describe a case of sarcoidosis manifesting as a unilateral posterior
      uveitis and retinal arteritis. DESIGN: Interventional case report. METHODS:
      Clinical examination, fluorescein angiography, radiological imaging, and
      laboratory testing revealed evidence of a primary arteritis associated with
      sarcoidosis. RESULTS: A 39-year-old white male presented with unilateral
      decreased vision, disc edema, exudative maculopathy, and retinal arteritis. Lab
      work and imaging were consistent with sarcoidosis. The patient responded to a 2
      month course of oral prednisone and a sub-Tenon's triamcinolone injection.
      CONCLUSIONS: Sarcoidosis should be considered in the differential diagnosis of
      uveitis associated with a primary retinal arteritis.

PMID- 20128643
TI  - Retinal vasculopathy associated with mixed connective tissue disease.
AB  - PURPOSE: To report an intractable case of retinal vasculopathy associated with
      mixed connective tissue disease (MCTD). DESIGN: Case report. METHODS:
      Interventional case report. RESULTS: A 35-year-old woman presented with decreased
      visual acuity and multiple retinal hemorrhages and macular edema in her right
      eye. She had a history of central retinal vein occlusion in the opposite eye and
      MCTD. Her clinical course deteriorated despite subsequent systemic and
      intravitreal steroid and immunosuppressant treatments. The retinal vasculopathy
      involved both artery and vein, causing wide retinal areas of nonperfusion. Her
      final visual acuity was hand motion. CONCLUSIONS: MCTD may be associated with
      bilateral vasculopathy that is refractory to systemic steroid, intravitreal
      steroid, and immunosuppressant treatment.

PMID- 20128644
TI  - Retinal vasculitis associated with the anti-synthetase syndrome.
AB  - A 50-year-old woman with a history of anti-Jo1-positive inflammatory myositis and
      interstitial lung disease presented with decreased vision in her right eye.
      Examination revealed white-centered hemorrhages scattered across the posterior
      pole in addition to several areas of vascular sheathing. Treatment was initiated
      with intravenous pulse solumedrol, with improvement in vision and resolution of
      the patient's white-centered hemorrhages. A thorough workup for other causes of
      vasculitis was unrevealing. Anti-synthetase syndrome is a serologically defined
      disorder clinically characterized by inflammatory myositis, interstitial lung
      disease, and other systemic findings. To our knowledge, retinal vasculitis has
      not been previously reported in patients with anti-synthetase syndrome.

PMID- 20128645
TI  - History and physiology of immune privilege.
AB  - Immune privilege is the condition in which selected immune responses are
      suppressed or excluded in certain organs, such as the eye. Immune privilege in
      the eye was described over 130 years ago, but its significance was not
      appreciated until the early 1950s. Investigations beginning in the 1970s ushered
      in a new era and revealed that ocular immune privilege is due to anatomical,
      physiological, and immunoregulatory processes that prevent the induction and
      expression of immune-mediated inflammation. It is widely believed that immune
      privilege is an adaptation for reducing immune-mediated injury to ocular cells
      that have limited or no capacity for regeneration.

PMID- 20128646
TI  - The role of indoleamine 2,3-dioxygenase in retinal pigment epithelial cell
      mediated immune modulation.
AB  - PURPOSE: To evaluate the role of indoleamine dioxygenase (IDO) in human retinal
      pigment epithelial cell (RPE)-mediated immune modulation. METHODS: The
      immunosuppression of cultured human RPEs (ARPE-19 cells) was assayed using the
      mixed lymphocyte reaction (MLR) harvested from CBA/J and BALB/c mice. The
      expression of critical immune modulatory molecules, such as class II major
      histocompatibility complex (MHC) molecules, co-stimulatory molecules (B7-1 and B7
      2), and indoleamine dioxygenase (IDO), was examined by reverse transcriptase
      polymerase chain reaction, flow cytometry, and immunofluorescence staining with
      and without IFN-gamma stimulation. RESULTS: RPEs expressed IDO and class II MHC
      molecules under IFN-gamma stimulation. However, B7-1 and B7-2 were not expressed.
      RPE significantly suppressed MLR in the absence of IFN-gamma prestimulation. This
      phenomenon was enhanced by IFN-gamma stimulation. The addition of 1-methyl
      tryptophan (1-MT) into the culture medium successfully reversed RPE
      immunosuppression. CONCLUSIONS: The expression of IDO may in part explain RPE
      mediated immune suppression effects.

PMID- 20128647
TI  - Anti-inflammatory activity of azithromycin as measured by its NF-kappaB,
      inhibitory activity.
AB  - Growing data suggest that the antibiotic azithromycin mediates anti-inflammatory
      activity through the inhibition of the transcription factor NF-kappaB. The
      purpose of this study was to compare azithromycin's anti-inflammatory potency
      with that of hydrocortisone and dexamethasone as measured in an activated NF
      kappaB assay. Dose-response curves and the corresponding inhibitory potencies
      (IC(50)) of azithromycin, hydrocortisone, and dexamethasone were evaluated in a
      fluorescence assay using A549 cells. All three compounds inhibited TNFalpha
      stimulated NF-kappaB activity in a dose-dependent manner. IC(50) values of
      azithromycin, hydrocortisone and dexamethasone were 56 microM, 2.6 nM, and 0.18
      nM, respectively. Hydrocortisone was approximately 4 orders of magnitude more
      potent than azithromycin, while dexamethasone was approximately 14 times as
      potent as hydrocortisone. In relative terms the anti-inflammatory potency of
      azithromycin was about 4 orders of magnitude weaker than that of hydrocortisone.

PMID- 20128648
TI  - Increased Regulatory T Cells in Spleen during Experimental Autoimmune
      Uveoretinitis.
AB  - PURPOSE: To investigate the role of Foxp3-positive regulatory T cells in the
      development of experimental autoimmune uveoretinitis (EAU). METHODS: B10RIII mice
      were immunized with 50 microg IRBP(161-180) in complete Freund's adjuvant (CFA)
      to induce EAU. EAU was evaluated clinically and pathologically on days 0, 7, 14,
      21, and 28. Foxp3 mRNA levels were detected using reverse transcription-PCR (RT
      PCR) and the frequencies of CD4(+)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) T
      cells in splenocytes were assessed by flow cytometry at the aforementioned time
      points. RESULTS: The first clinical signs of EAU were observed on day 8-9,
      worsened up to day 14, and then gradually resolved. Histopathologic results
      showed that inflammatory signs occurred on day 7, reached their peak on day 14,
      and then gradually decreased. The levels of Foxp3 mRNA and the frequencies of
      CD4(+)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells in splenocytes increased
      on day 7, reached a peak on day 14, and then maintained at a high level until day
      28. CONCLUSION: An upregulation of Foxp3 expression is induced in EAU and
      paralleled with disease activity, suggesting a role for this lymphocyte
      subpopulation in the regression of this experimental uveitis model.

PMID- 20128649
TI  - Mutton fat-like subretinal precipitates associated with Vogt-Koyanagi-Harada
      disease.
AB  - PURPOSE: To report a case of Vogt-Koyanagi-Harada (VKH) disease presenting mutton
      fat like subretinal precipitates. DESIGN: Observational case report. METHODS: A
      52-year-old Japanese woman developed bilateral uvetis with serous retinal
      detachment and mutton fat like subretinal precipitates. RESULTS: According to
      Opthalmologic, auditory, and systemic examination, we diagnosed the patient with
      VKH disease. Inflamation was controlled by three time steroid therapy and
      subretinal fluid and precipitates decreased and disappeared. CONCLUSIONS:
      Subretinal granulomatous lesion may present a manifestation of VKH and mean long
      standing subretinal fluid and inflammation.

PMID- 20128650
TI  - Clinical profile, treatment, and visual outcome of ampiginous choroiditis.
AB  - PURPOSE: To report the clinical profile and management of patients diagnosed to
      have ampiginous choroiditis in a tertiary care referral centre in India. METHODS:
      Retrospective cohort study. Twenty-six eyes of 16 patients were included in the
      study, which was diagnosed as choroiditis, serpiginous choroiditis, and acute
      posterior multifocal placoid pigment epitheliopathy (APMPPE) or ampiginous
      choroiditis. Those who were initially diagnosed as having other forms of
      choroiditis were later classified as having ampiginous choroiditis clinically.
      Systemic steroids and immunosuppressives were the mainstay of therapy. RESULTS:
      There was a male preponderance (7:3). Age at presentation ranged from 22 years to
      57 years with a (median 34 years); 81% had bilateral involvement and 35% had
      recurrences. Vision improved or maintained in 24 eyes, whereas it deteriorated in
      2 eyes due to subretinal fibrosis and macula involvement, respectively.
      Resolution of lesions and improvement or stability of vision can occur with
      administration of timely steroids and immunosuppressive therapy. Regular follow
      up is necessary to monitor the disease progression, recurrences, and involvement
      of the other eye. CONCLUSION: Ampiginous choroiditis is a separate disease entity
      due to its distinct clinical features. It is a disease with multiple relapses,
      which can be effectively controlled with a combination of immunosuppressive
      therapy, and a good visual acuity can be maintained on long-term follow-up.

PMID- 20128651
TI  - Reactive arthritis following Streptococcus viridans urinary tract infection.
AB  - PURPOSE: To report a case with reactive arthritis (ReA) following Streptococcus
      viridans genitourinary infection. METHODS: Case report. DESIGN: Clinical findings
      and treatment are presented. The 28-year-old man visited the authors' hospital
      due to ciliary injection and hypopyon over left eye. On examination, Behcet
      mimicking symptoms were observed, such as genital and oral ulcers and arthritis.
      Furthermore, S. viridans was found in the urethral discharge culture. Under the
      impression of ReA, which was triggered by S. viridans, NSAID and antibiotics were
      prescribed. Complete resolution of ocular and systemic symptoms was achieved
      after 2 months of treatment. CONCLUSIONS: Streptococcus viridans is potential
      microorganisms of ReA. Careful survey and prompt treatment is necessary.

PMID- 20128652
TI  - Retinal complications of juvenile idiopathic arthritis-related uveitis: a
      microperimetry and optical coherence tomography study.
AB  - PURPOSE: To evaluate ocular complications of juvenile idiopathic arthritis (JIA)
      related uveitis; to study macular morphology and sensitivity. METHODS:
      Retrospective chart review of 67 patients. Fourteen consecutive patients (24
      eyes) observed from January to December 2008 were submitted to optical coherence
      tomography study (OCT) and microperimetry MP-1 examination. RESULTS: Most
      frequent complications were posterior synechiae (63.0%), band keratopathy
      (53.9%), and cataract (31.8%). Posterior complications were documented in 37.0%
      of eyes: 13.8% macular edema, 12.0% papillitis, 6.8% epiretinal membranes, 2.5%
      retinal vasculitis, 1.7% retinal detachment. At OCT examination 25.0% of eyes
      presented macular edema; macular sensitivity by MP-1 was < or = 16.5 dB in 25.0%
      of eyes. CONCLUSIONS: Visual prognosis is good despite ocular complications.
      Incidence of macular edema seems to be higher when using OCT. Microperimetry may
      represent a useful tool in detecting alteration in retinal sensitivity that may
      supplement visual acuity in the follow-up of macular edema.

PMID- 20128653
TI  - Nonprogressive tractional inferior retinal elevation in intermediate uveitis.
AB  - PURPOSE: To describe inferior peripheral retinal elevations associated with
      intermediate uveitis. METHODS: Retrospective review. RESULTS: Eleven eyes of 7
      patients developed inferior retinal elevation secondary to intermediate uveitis.
      Six eyes (54.6%) were believed to have tractional retinoschisis, 2 (18.2%) had
      tractional retinal detachment, and the remaining 3 (27.3%) had flat retinal
      elevation of indeterminate type. In 10 eyes there was no evidence of progression
      during a mean 4-year follow-up. One eye developed extended tractional elevation
      with macular pucker and failed to respond to surgery. At the most recent visit,
      visual acuity ranged from 6/5 to NPL with a median of 6/12. CONCLUSION:
      Intermediate uveitis may cause inferior peripheral retinal elevation. The authors
      propose that preretinal and pars plana gliosis resulting from chronic pars
      planitis exerts traction on peripheral retina, causing elevation, but infer that
      such elevation removes traction and is self-limiting. Surgery should be reserved
      only for macula threatening lesions.

PMID- 20128654
TI  - Bilateral toxoplasma retinochoroiditis in a patient with chronic myeloid leukemia
      treated with imatinib mesylate.
AB  - A 48-year-old man, on imatinib therapy for chronic myeloid leukemia, developed
      bilateral retino-choroiditis. Visual acuity was 20/100 and counting fingers at 2
      m in both the right and left eye. Vitreous biopsy (left eye) revealed Toxoplasma
      gondii genome by polymerase chain reaction. Serum anti-toxoplasma IgG levels were
      significantly elevated. Blood counts were normal. Bcr-Abl/Abl transcript ratio
      was 0.016%. He was treated with oral co-trimoxazole, to which corticosteroids in
      tapering doses were added later. Imatinib therapy was continued. After 6 weeks of
      therapy, all retinal lesions regressed and vision improved to 20/30 and 20/40 in
      right and left eyes, respectively.

PMID- 20128656
TI  - Hot water extracts of Chlorella vulgaris improve immune function in protein
      deficient weanling mice and immune cells.
AB  - The objective of this study was to investigate the effects of hot water extracts
      of Chlorella vulgaris (CVE) on a deteriorated immune function through utilization
      of a protein-energy malnutrition (PEM) diet. Unicellular algae, C. vulgaris, were
      used as biological response modifier. PEM is associated with decreased host
      immune defense. Male C57BL/6J mice, initially four weeks old, were fed for 8 days
      with standard diet or a PEM diet. Mice in the PEM diet group were orally
      administered 0.1 g/kg and 0.15 g/kg of CVE for the following week. Nutritional
      parameters such as the total protein, albumin, glucose, and interferon gamma (IFN
      gamma) were increased in blood serum of the CVE-treated group compared with the
      non-treated group. The mononuclear cell numbers from spleen, superficial, and
      mesenteric lymph node were reduced in mice fed with PEM diet, but numbers from
      the spleen and superficial lymph node were increased by the CVE (0.1 and 0.15
      g/kg) treatment. We also investigated the effect of CVE on the production of
      cytokines in human T-cell line, MOLT-4 cells, and primary cultured splenocytes.
      The CVE treatment significantly increased the production of both interleukin (IL)
      2 and IL-4 compared with the media control, but did not affect the production of
      IFN-gamma. These results suggest that CVE may be useful in improving the immune
      function.

PMID- 20128657
TI  - A chimeric vitronectin: IGF-I protein supports feeder-cell-free and serum-free
      culture of human embryonic stem cells.
AB  - The therapeutic use of human embryonic stem (hES) cells is severely limited by
      safety concerns regarding their culture in media containing animal-derived or
      nondefined factors and on animal-derived feeder cells. Thus, there is a pressing
      need to develop culture techniques that are xeno-free, fully defined, and
      synthetic. Our laboratory has discovered that insulin-like growth factor (IGF)
      and vitronectin (VN) bind to each other resulting in synergistic short-term
      functional effects in several cell types, including keratinocytes and breast
      epithelial cells. We have further refined this complex into a single chimeric
      VN:IGF-I protein that functionally mimics the effects obtained upon binding of
      IGF-I to VN. The aim of the current study was to determine whether hES cells can
      be serially propagated in feeder-cell-free and serum-free conditions using medium
      containing our novel chimeric VN:IGF-I protein. Here we demonstrate that hES
      cells can be serially propagated and retain their undifferentiated state in vitro
      for up to 35 passages in our feeder-cell-free, serum-free, chemically defined
      media. We have utilized real-time polymerase chain reaction (PCR),
      immunofluorescence, and fluorescence-activated cell sorter (FACS) analysis to
      show that the hES cells have maintained an undifferentiated phenotype. In vitro
      differentiation assays demonstrated that the hES cells retain their pluripotent
      potential and the karyotype of the hES cells remains unchanged. This study
      demonstrates that the novel, fully defined, synthetic VN:IGF-I chimera-containing
      medium described herein is a viable alternative to media containing serum, and
      that in conjunction with laminin-coated plates facilitates feeder-cell-free and
      serum-free growth of hES.

PMID- 20128658
TI  - Treatment of systemic lupus erythematosus in two patients with extreme B-cell
      lymphopenia: importance of immunomonitoring and avoidance of B-cell targeted
      therapy.
AB  - INTRODUCTION: Because dysfunction of the B-cell compartment is thought to be
      important in the pathogenesis of systemic lupus erythematosus (SLE), there has
      been a recent focus on therapies that target humoral immunity via multiple
      mechanisms. The aim of this paper was to demonstrate the importance of
      immunomonitoring in two cases with class II lupus nephritis on steroids who
      presented with a flare-up of disease. After a thorough work-up for infectious
      triggers of disease activity, conversion to another histopathological class of
      lupus nephritis was suspected. Deterioration of the patients' clinical condition
      made kidney biopsy impossible, and as B-cell targeted therapy was considered, we
      decided to perform an immunophenotypic analysis and to tailor therapy to the
      results of the lymphocyte profile. As we incidentally found extremely low B-cell
      counts, any B-cell-targeted therapy was prohibited, and cyclophosphamide (Cy) was
      considered a viable therapeutic option. METHODS: We performed flow-cytometric
      lymphocyte (Ly) phenotyping (CD19, CD3, CD3CD4, CD3CD8, CD56/16) on two patients
      with class II lupus nephritis before and after two intravenous (i.v.) Cy pulse
      administrations. During all this time, patients were on steroids. RESULTS:  Both
      patients showed extreme B-cell lymphopenia, a marker of active SLE, which was not
      greatly impacted by the treatment over the follow-up period. CONCLUSIONS: As
      current therapies are aimed at targeting the B cell, an important component of
      adaptive immunity, caution must be exercised before their use. In addition,
      monitoring of Ly subsets is essential due to the occurrence of extreme B-cell
      lymphopenia.

PMID- 20128660
TI  - 17beta-Estradiol increases the number of effector memory CD8+ lymphocytes in mice
      with contact hypersensitivity and among cultured splenocytes.
AB  - To determine how estrogen exacerbates allergies, the effects of 17beta-estradiol
      (E2) on lymphocyte proliferation were investigated. BALB/c mice were
      ovariectomized, administered 3.2 microg E2, and sensitized with 50 microL 4
      ethoxymethylene-2-phenyl-2-oxazolin-5-one. After 7 days, their spleens were
      excised and flow cytometrically analyzed. The CD8(+)CD45RA(-)CCR7(-) cell-to
      CD8(+) cell ratio in the spleen was greater in the E2-administered mice than in
      the controls. Splenocytes were cultured under concanavalin A stimulation, with or
      without E2. After 4 days, the above ratio was greater in the case of E2-treated
      splenocytes. E2 increases the number of effector memory CD8(+) lymphocytes during
      sensitization in contact hypersensitivity.

PMID- 20128659
TI  - Characterization of microRNAs involved in embryonic stem cell states.
AB  - Studies of embryonic stem cells (ESCs) reveal that these cell lines can be
      derived from differing stages of embryonic development. We analyzed common
      changes in the expression of microRNAs (miRNAs) and mRNAs in 9 different human
      ESC (hESC) lines during early commitment and further examined the expression of
      key ESCenriched miRNAs in earlier developmental states in several species. We
      show that several previously defined hESC-enriched miRNA groups (the miR-302, 
      17, and -515 families, and the miR-371-373 cluster) and several other hESC
      enriched miRNAs are down-regulated rapidly in response to differentiation. We
      further found that mRNAs up-regulated upon differentiation are enriched in
      potential target sites for these hESC-enriched miRNAs. Interestingly, we also
      observed that the expression of ESC-enriched miRNAs bearing identical seed
      sequences changed dynamically while the cells transitioned through early
      embryonic states. In human and monkey ESCs, as well as human-induced pluripotent
      stem cells (iPSCs), the miR-371-373 cluster was consistently up-regulated, while
      the miR-302 family was mildly down-regulated when the cells were chemically
      treated to regress to an earlier developmental state. Similarly, miR-302b, but
      not mmu-miR-295, was expressed at higher levels in murine epiblast stem cells
      (mEpiSC) as compared with an earlier developmental state, mouse ESCs. These
      results raise the possibility that the relative expression of related miRNAs
      might serve as diagnostic indicators in defining the developmental state of
      embryonic cells and other stem cell lines, such as iPSCs. These data also raise
      the possibility that miRNAs bearing identical seed sequences could have specific
      functions during separable stages of early embryonic development.

PMID- 20128661
TI  - Identification of a common gene expression signature associated with immature
      clonal mesenchymal cell populations derived from bone marrow and dental tissues.
AB  - Mesenchymal stem/stromal cell-like populations derived from adult bone marrow
      (BMSC), dental pulp (DPSC), and periodontal ligament (PDLSC) have the ability to
      differentiate into cells of mesenchymal and non-mesenchymal tissues in vitro and
      in vivo. However, culture-expanded MSC-like populations are a heterogeneous mix
      of stem/committed progenitor cells that exhibit altered growth and developmental
      potentials. In the present study we isolated and characterized clonal populations
      of BMSCs, DPSCs, and PDLSCs to identify potential biomarkers associated with long
      lived multipotential stem cells. Microarray analysis was used to compare the
      global gene expression profiles of high growth/multipotential clones with low
      growth potential cell clones derived from 3 stromal tissues. Cross-comparison
      analyses of genes expressed by high growth/multipotential clones derived from
      bone marrow, dental pulp, and periodontal ligament identified 24 genes that are
      differentially up-regulated in all tissues. Notably, the transcription factors,
      E2F2, PTTG1, TWIST-1, and transcriptional cofactor, LDB2, each with critical
      roles in cell growth and survival, were highly expressed in all stem cell
      populations examined. These findings provide a model system for identifying a
      common molecular fingerprint associated with immature mesenchymal stem-like cells
      from different organs and implicate a potential role for these genes in MSC
      growth and development.

PMID- 20128662
TI  - Quality of life in relation to constipation among opioid users.
AB  - OBJECTIVE: Opioid users often experience constipation. In this study the impact
      of constipation on QoL was assessed in patients using opioids either for non
      advanced illness or advanced illness. METHODS: Patients using opioids, recruited
      via public pharmacies, were asked to complete questionnaires on opioid use,
      constipation and the EuroQol five-dimension questionnaire (EQ-5D). Patients with
      a severe non-curable disease and relatively short life-expectancy were classified
      as having an advanced illness; a disabling yet not directly life-threatening
      condition was defined as non-advanced illness. Constipation was assessed based on
      questions on opioid side-effects and laxative use. EQ-5D index scores were
      compared between patients with and without constipation using Wilcoxon two
      samples test. RESULTS: Questionnaires were returned by 588 patients with non
      advanced illness, of whom 326 (55%) were classified as having constipation and by
      113 patients with advanced illness, of whom 76 (67%) were classified as having
      constipation. The median EQ-5D index, a weighted health state index score with 1
      = full health, was lower in patients with constipation than in patients without
      constipation (0.31 vs. 0.65, p< 0.01 for non-advanced illness and 0.41 vs. 0.61,
      p=0.12 for advanced illness). CONCLUSION: The results of this study suggest that,
      in patients using opioids either for non-advanced illness or advanced illness,
      constipation negatively influences QoL. By separately analysing patients with
      advanced illness and patients with non-advanced illness, possible selective non
      response and confounding was accounted for, but not completely solved.

PMID- 20128663
TI  - Comparative costs of hospitalisation among infants at high risk for respiratory
      syncytial virus lower respiratory tract infection during the first year of life.
AB  - OBJECTIVE: This retrospective cohort study compared the total cost of
      hospitalisation due to respiratory syncytial virus (RSV) lower respiratory tract
      infection (LRI) during the first year of life between late-preterm (33-36 weeks
      gestational age [wGA]) and term (>= 37 wGA) infants. RESEARCH DESIGN AND METHODS:
      A large national claims database of commercially insured members was examined to
      identify hospital admissions associated with RSV between January 2003 and June
      2007 among infants at high risk for RSV LRI, including late-preterm infants.
      Hospital use and costs were compared with those of a reference cohort of term
      infants with RSV. RESULTS: The cost of hospitalisation for RSV among late-preterm
      infants with at least one hospital admission associated with RSV (n=173) was
      twice that of term infants (n=1,983; $20,269 vs. 9,635; p< 0.001). The mean
      length of stay was also higher (5.3 vs. 3.4 days; p< 0.001). Approximately 21.9%
      of hospitalisations for late-preterm infants included an intensive care unit
      admission compared with 9.6% among term infants (p< 0.001). LIMITATIONS: Reliance
      on ICD-9 codes to identify potential cohort members may result in
      misclassification and underreporting the cohort size for conditions of interest.
      CONCLUSIONS: Hospitalisation costs and length of stay due to RSV LRI were
      significantly greater among late-preterm infants compared with term infants and
      higher than general estimates previously reported in the broader paediatric
      population.

PMID- 20128664
TI  - Effect of internal iliac artery ligation on ovarian blood supply and ovarian
      reserve.
AB  - BACKGROUND: Internal iliac artery ligation is one of the treatment methods used
      for obstetric hemorrhage. The long-term effects of that intervention on ovarian
      function remain unknown. The objective of the study was to evaluate the effect of
      iliac artery ligation on ovarian blood supply and ovarian reserve. METHODS: Six
      patients who had undergone internal iliac artery ligation were recruited as the
      study group. Six women of the same age, parity and time after delivery who had
      not undergone the internal iliac artery ligation procedure served as the control
      group. Quantitative digital angiography and angio-CT of the ovarian arteries and
      the ovarian branches of the uterine arteries were carried out from 6 to 26 months
      after the operation. Blood samples were taken on the 3rd day of the menstrual
      cycle for subsequent hormone analysis of follicle stimulating hormone (FSH) and
      anti-Mullerian hormone (AMH). RESULTS: Following angio-CT, in the study group,
      reversed blood flow in the ovarian branches of the uterine arteries was observed:
      contrast medium flowed from the ovarian arteries towards the ovaries and from the
      ovarian branches of the uterine arteries to the uterine arteries. In the control
      group, there was no contrast medium flow from the ovaries towards the ovarian
      branches of the uterine arteries. Quantitative digital angiography of the ovarian
      arteries showed that, in the study group, the mean ovarian artery diameter was
      significantly dilated (p < 0.05). In the study group, AMH levels were
      significantly lower (p < 0.05), while there were no significant differences in
      FSH levels between groups (p > 0.05). CONCLUSIONS: Internal iliac artery ligation
      in the treatment of obstetric hemorrhage leads to dilation of the ovarian
      arteries and reversed flow in the ovarian branches of the uterine arteries. These
      change the blood supply to the ovaries and impair ovarian reserve.

PMID- 20128665
TI  - A new way of targeting to treat nerve injury.
AB  - Although neurons within the peripheral nervous system have a remarkable ability
      to repair themselves after injury, neurons within the central nervous system do
      not spontaneously regenerate. This problem has remained recalcitrant despite a
      century of research on the reaction of axons to injury. The balance between
      inhibitory cues present in the environment and the intrinsic growth capacity of
      the injured neuron determines the extent of axonal regeneration following injury.
      The cell body of an injured neuron must receive accurate and timely information
      about the site and extent of axonal damage in order to increase its intrinsic
      growth capacity and regenerate successfully. One of the mechanisms contributing
      to this process is retrograde transport of injury signals. For example, molecules
      activated at the injury site convey information to the cell body leading to the
      expression of regeneration-associated genes and increased growth capacity of the
      neuron. In this paper, we are introducing therapeutic agents to treat brain
      injury and peripheral nerve injury. Since glial cell adhesion molecule is
      upregulated in gliotic scar, it is possible to target therapeutic agents to the
      site of brain injury. This directed therapy presents an innovative and promising
      therapy.

PMID- 20128666
TI  - Activity-rest rhythm abnormalities in Parkinson's disease patients are related to
      dopaminergic therapy.
AB  - OBJECTIVES: To compare going to bed, waking-up, and immobility onset and offset
      times in Parkinson's disease (PD) patients receiving levodopa and/or dopamine
      agonists (i.e., dopaminergic therapy or DT) with "de novo" patients and healthy
      controls and to correlate these parameters with self-reported sleep disturbances.
      METHODS: Fifteen "de novo" and 60 PD patients on DT were included in the study.
      Twenty-three subjects without history of sleep complaints and similar age and sex
      distributions as the PD patients served as controls. Going to bed and waking-up
      times were registered in 7-day sleep logs. Nocturnal immobility onset and offset
      times were measured using actigraphy. Sleep disorders were assessed applying the
      PD sleep scale (PDSS). RESULTS: Patients on DT showed earlier waking-up and
      immobility offset times (40 min) compared with controls and "de novo" patients.
      Multivariable regression analysis showed that DT but not Hoehn & Yahr score was a
      significant and independent predictor of early awakening time (OR = 4.0, 95% CI =
      1.15-14.13). Patients manifesting more frequent nighttime psychotic symptoms and
      more frequent daytime somnolence showed earlier going to bed and waking-up times.
      CONCLUSIONS: Results suggest that activity-rest rhythm alteration in PD may be a
      consequence of DT but not of disease stage. Altered sleep cycles correlated with
      diurnal somnolence and nocturnal psychosis.

PMID- 20128667
TI  - Ice application effects on peroneus longus and tibialis anterior motoneuron
      excitability in subjects with functional ankle instability.
AB  - Evidence that focally cooling the ankle joint facilitates soleus and peroneus
      longus spinal reflex activity in healthy subjects has been reported. This
      response has been confirmed in individuals with a history of joint pathology for
      the soleus but not in the peroneus longus and tibialis anterior. The purpose of
      this study was to identify the effects of ankle cooling on isokinetic eversion
      and inversion torque and in peroneus longus, tibialis anterior H-reflex
      (H(max):M(max)) in subjects with functional ankle instability (FAI). Twenty-four
      college aged subjects volunteered for this study. Peroneus longus and tibialis
      anterior H(max):M(max), and concentric eversion and inversion torque were
      recorded prior to and following each session. This protocol was used to compare
      FAI to healthy ankle group. There were no significant differences between groups.
      There were weak and no significant relationships between the corresponding
      muscles motoneuron excitability and their peak torque measurements. Ice
      application to the joint did not alter the peroneus longus or the tibialis
      anterior.

PMID- 20128668
TI  - Cranial magnetic resonance imaging findings in kwashiorkor.
AB  - Protein energy malnutrition (PEM) is an important public health problem in the
      developing countries, although it is becoming uncommon in South West Nigeria.
      Cerebral changes have been associated with severe PEM. This study evaluated the
      neurological changes using Magnetic Resonance Imaging (MRI) in Ibadan south west
      Nigeria. The 5 children evaluated had a median age of 16 months and all the
      children had brain changes compatible with cerebral atrophy. In addition two of
      the children had periventricular white matter changes, while one these two had
      mega cisterna magna in addition. Though this study did not re-evaluate the brains
      of these children after nutritional rehabilitation, it is possible that changes
      are reversible as demonstrated in earlier studies.

PMID- 20128669
TI  - A simplified screening protocol predicts pathological electroneurographic results
      in patients with suspected polyneuropathy.
AB  - Electroneurographic testing is one of the standard instruments to detect
      polyneuropathy (PNP). The objective of this study was to develop a screening tool
      with optimized sensitivity and specificity, consisting of a short questionnaire
      and a short standardized neurological examination. One hundred one patients with
      a suspected PNP were prospectively selected from the neurological outpatient
      clinic. We used a short questionnaire and a short neurological examination
      derived from the Michigan Neuropathy Screening Instrument (MNSI). Based on
      electroneurographic results, patients were classified in three groups of
      different severity. The diagnostic power of the MNSI was optimized by
      constructing a score based on two combined discrimination functions. The
      optimized screening tool was able to detect patients suffering from PNP at a
      sensitivity of 88%. In particular, a severe form of PNP was recognized at a
      sensitivity of 97%. The specificity to detect healthy subjects was 74%. This new
      tool is a fast and easy to use instrument which can give a decision support for
      general practitioners for patients with a suspected PNP as to whether a
      subsequent electroneurographical examination (ENG) testing will show pathological
      results.

PMID- 20128670
TI  - Olfaction in the elderly: a cross-sectional analysis comparing Parkinson's
      disease with controls and other disorders.
AB  - Olfactory dysfunction in Parkinson's disease (PD) is an association that has been
      well documented in the medical literature, although the underlying
      pathophysiologic mechanism has not been clearly elucidated. In the Sun Health
      Research Institute Brain and Body Donation Program, subjects were tested for
      olfactory function. Olfaction was impaired in subjects with clinically probable
      PD but not those with essential tremor (ET), restless legs syndrome (RLS), or
      mild cognitive impairment. In the elderly control population there were no
      differences between genders and the UPSIT score decreased by 3.2 points per
      decade. These data confirm previous findings in PD, ET, and RLS, and expand the
      data for an elderly control population.

PMID- 20128671
TI  - Increasing contextual demand modulates anterior and lateral prefrontal brain
      regions associated with proactive interference.
AB  - Using a parametric version of a modified item-recognition paradigm with three
      different load levels and by means of event-related functional magnetic resonance
      imaging, this study tested the hypothesis that cerebral activation associated
      with intratrial proactive interference (PI) during working memory retrieval is
      influenced by increased context processing. We found activation of left BA 45
      during interference trials across all levels of cognitive processing, and left
      lateralized activation of the dorsolateral prefrontal cortex (DLPFC, BA 9/46) and
      the frontopolar cortex (FPC, BA 10) with increasing contextual load. Compared
      with high susceptibility to PI, low susceptibility was associated with activation
      of the left DLPFC. These results suggest that an intratrial PI effect can be
      modulated by increasing context processing of a transiently relevant stimulus
      set. Moreover, PI resolution associated with increasing context load involves
      multiple prefrontal regions including the ventro- and dorsolateral prefrontal
      cortex as well as frontopolar brain areas. Furthermore, low susceptibility to PI
      might be influenced by increased executive control exerted by the DLPFC.

PMID- 20128672
TI  - Working memory deficit in dyslexia: behavioral and FMRI evidence.
AB  - Dyslexia is a condition characterized by difficulty of reading given adequate
      intelligence and educational opportunities, primarily associated with a
      phonological processing deficit. In this study we show that dyslexic children
      also show a deficit in working memory compared to a control group, measured with
      fMRI. A working memory n-back task with three load levels was used. Behavioral
      data showed that the dyslexics had poorer performance compared to the controls.
      fMRI data showed that the dyslexics had reduced activation in the prefrontal and
      parietal cortices and the cerebellum compared with the controls. These results
      imply a working memory deficit in dyslexia.

PMID- 20128673
TI  - Functional MRI-based therapeutic rTMS strategy for aphasic stroke patients: a
      case series pilot study.
AB  - Four poststroke patients with motor-dominant aphasia received 10 treatment
      sessions of low-frequency repetitive transcranial magnetic stimulation (rTMS).
      Each treatment session consisted of 1,200 pulses of stimulation and the site of
      stimulation was an area homologous to the most activated site on functional MRI
      performed prior to rTMS. Consequently, rTMS was applied to the right frontal lobe
      in two patients and to the left frontal lobe in two patients. Treatment resulted
      in improvement of language function in all four patients. Our therapeutic rTMS
      strategy seems to be a clinically feasible neurorehabilitative approach for
      poststroke aphasic patients.

PMID- 20128674
TI  - The relationship between anosmia, constipation, and orthostasis and Parkinson's
      disease duration: results of a pilot study.
AB  - Autonomic symptomatology is prevalent in Parkinson's disease (PD) and impacts
      quality of life, yet little data exist on the presentation of autonomic
      dysregulation. This study measures orthostasis, constipation, and anosmia in 58
      PD patients and 51 age-matched controls enrolled in the University of Florida's
      Movement Disorders Center. Patients had their blood pressure measured while
      seated and in standing position, performed the University of Pennsylvania Smell
      Identification Test (UPSIT), and completed a constipation survey. Our PD patients
      had a significantly different average decrease in systolic BP from a seated to
      standing position compared with their age-matched controls (5.90 mmHg (SD 17.03)
      vs. 2.6 mmHg (SD 11.28); p = .05). The difference in heart rate from seated to
      standing positions was not significant. Reflexive tachycardia was inversely
      proportional to levodopa equivalent daily dose (LEDD) score (p = .002). Anosmia
      occurred in 96.4% of the PD group and 49% of the controls (p < .001).
      Constipation was also more prevalent in the PD population than in the controls
      (67.3% vs. 21.6%; p < .001). Both anosmia and constipation were correlated with
      disease duration (p = .038 and .04 respectively). Our study suggests that
      increasing levels of dopaminergic therapy inhibits reflexive tachycardia.
      Furthermore, our study suggests that anosmia and constipation progress with the
      primary disease process.

PMID- 20128675
TI  - Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica
      patients.
AB  - Anti-aquaporin-4 (Aqp-4) antibody and complement system have emerged as major
      pathogenic factors in neuromyelitis optica (NMO). To test the significance of
      interleukin-6 (IL-6), another important humoral immunity factor, in NMO
      pathogenesis, we measured serum and cerebrospinal fluid (CSF) IL-6 levels of 23
      NMO, 11 transverse myelitis, 16 optic neuritis, 27 relapsing remitting multiple
      sclerosis patients, and 20 neurologically normal controls. NMO and transverse
      myelitis patients had higher serum and CSF IL-6 levels than other groups.
      Particularly, anti-Aqp-4 positive NMO patients (n = 12) had higher serum/CSF IL-6
      levels than anti-Aqp-4 negative patients (n = 11) and CSF IL-6 levels correlated
      with anti-Aqp-4 levels and disease severity of the NMO patients. Our results
      suggest that IL-6 is involved in NMO pathogenesis presumably via anti-Aqp-4
      associated mechanisms.

PMID- 20128676
TI  - Comparison of conduction velocities of nerve fibers to smaller and larger muscles
      in rats.
AB  - The aim of this study was to compare conduction velocities of motor fibers to
      smaller and larger muscles and to investigate the advantages and disadvantages of
      recordings from the gastrocnemius muscle with surface electrodes over the
      recordings from small foot muscles (interosseous muscles) with needle electrodes
      in rats. Surface and needle recordings are suitable in measuring the motor
      conduction velocity of the sciatic (tibial) nerve. It should be noted that the
      motor velocity measured from the gastrocnemius muscle is higher than the motor
      velocity elicited from small foot muscles. Surface recordings provide information
      on the amplitude and duration of M responses.

PMID- 20128677
TI  - Interactions between endothelial cells and epithelial cells in a combined cell
      model of airway mucosa: effects on tight junction permeability.
AB  - Environmental particulates impact first on airway epithelium, whereas circulating
      infiltrating cells are recruited through the underlying endothelium. An effective
      cellular immune response requires coordination between endothelium and
      epithelium. The authors have developed a bilayer culture model consisting of
      human bronchial epithelial derived cells (16HBE 14o-) and human umbilical vein
      endothelial cells (HUVECs) cultured as confluent layers on either side of a
      porous membrane. Confocal microscopy with epithelial and endothelial-specific
      antibodies showed segregated cell layers. By scanning and transmission electron
      microscopy, both cell types are polarized and tight junctions formed at the
      apical interface between cells. Epithelial cells grown in a bilayer showed
      significantly increased transepithelial resistance (TER) of 2260 +/- 64
      Omega.cm(2) compared to epithelial or endothelial monolayers alone (1400 +/- 70
      or 80 +/- 12 Omega.cm(2), respectively). This reflected decreased permeability
      and was unrelated to cell density or height. Increased TER coincided with
      increased occludin mRNA and protein in the epithelial cell layer as determined by
      polymerase chain reaction (PCR) and immunoblotting. Conditioned medium showed
      that decreased permeability was mediated by soluble endothelial-derived
      factor(s). This model reflects the in vivo relationship of human airway
      endothelial cells and epithelial cells. Altered tight junction permeability in
      cocultures indicates that these cells can work together as an active part of the
      mucosal barrier.

PMID- 20128678
TI  - Tumor necrosis factor-alpha enhances both epithelial-mesenchymal transition and
      cell contraction induced in A549 human alveolar epithelial cells by transforming
      growth factor-beta1.
AB  - Recently, epithelial-mesenchymal transition (EMT) has been reported to contribute
      to tissue fibrosis through enhanced transforming growth factor (TGF)-beta1
      signaling. Tumor necrosis factor (TNF)-alpha has also been implicated in tissue
      fibrosis. Therefore, the authors investigated whether TNF-alpha affected TGF
      beta1-induced EMT. Cultured alveolar epithelial cells (A549 cells) were
      stimulated with TGF-beta1 (5 ng/mL), with/without TNF-alpha (10 ng/mL). TGF-beta1
      induced EMT of A549 cells, with loss of E-cadherin and acquisition of vimentin.
      Combination of TNF-alpha with TGF-beta1 enhanced EMT, causing morphological
      changes, while quantitative polymerase chain reaction (PCR) showed suppression of
      E-cadherin mRNA and expression of vimentin mRNA. In addition, the gel contraction
      method revealed that cells that had undergone EMT acquired cell contractility,
      which is a feature of mesenchymal cells. Stimulation with TGF-beta1 induced cell
      contraction, as did TNF-alpha. Moreover, costimulation with TGF-beta1 and TNF
      alpha enhanced the cell contraction. Although IFN-gamma suppressed spontaneous
      cell contraction, it did not suppress cell contraction, which was induced by TGF
      beta1. In conclusion, TNF-alpha enhances not only EMT but also cell contraction
      induced by TGF-beta1. EMT might contribute to tissue fibrosis through induction
      of cell contraction.

PMID- 20128679
TI  - Left-sided mouse intubation: description and evaluation.
AB  - A method of left main bronchus intubation was developed based on a wire guide
      based microscopic endotrachael mouse intubation technique. The authors used a 22
      G x 1 inch catheter elongated by a 38-mm silicone tube, and a wire guide with a
      tag to assign the length of the wire completely covered by the silicon tube. The
      isoflurane-anesthetized mouse was hung perpendicularly with its incisors on a
      thread and transorally intubated under strict vision with the wire guide tip
      advanced 3 mm out of the catheter. Then the catheter was advanced about 6 to 8 mm
      into the trachea. Afterwards the wire guide was redrawn to the level of the
      catheter tip (blue tag on the wire guide appeared at the upper end of catheter)
      to prevent injury. Then the neck was pushed into a right lateral flexion with one
      finger against a foam block fixed on the vertical plate, causing a straight
      distance between mouth and left main bronchus. This positioning allows to gently
      advance the catheter into the left main bronchus by another about 20 mm, using
      the wire guide with its tip just within the tube, to achieve there a wedge
      position with gentle pressure.The technique had a success rate of more than 80%
      in 81 mice weighing 23 to 48 g. It may be of interest for unilateral lung
      intervention, e.g., with injurious substances or with drugs.

PMID- 20128680
TI  - Alteration in the expression of inflammatory parameters as a result of oxidative
      stress produced by moderate zinc deficiency in rat lung.
AB  - Suboptimal intake of dietary zinc (Zn) is one of the most common nutritional
      problems worldwide. Previously, the authors have shown that zinc deficiency (ZD)
      produces oxidative and nitrosative stress in lung of male rats. The goal of this
      study is to test the effect of moderate ZD on insulin-like growth factor (IGF)-1,
      IGF-binding protein (IGFBP)-5, NADH oxidase (NOX)-2, tumor necrosis factor alpha
      (TNFalpha), as well as the effect of restoring zinc during the refeeding period.
      Adult male rats were divided into 3 groups: Zn-adequate control group, Zn
      deficient group, and Zn-refeeding group. eNOS, metallothionein (MT) II, and NOX-2
      was increased in ZD group. The authors observed an increased gene transcription
      of superoxide dismutase (SOD)-2 and gluthathione peroxidase (GPx)-1 in ZD group,
      as well as in ZD-refeeding group, but catalase (CAT) transcription did not change
      in the treated groups. Proinflammatory factors, such as TNFalpha and vascular
      cell adhesion molecular (VCAM)-1 increased in ZD, whereas it decreased in ZD
      refeeding. However, peroxisome proliferator-activated receptor gamma (PPARgamma)
      and IGF-1 gene transcription decreased in ZD, whereas IGFBP-5 decreased in the ZD
      group. These parameters are associated to alterations in the lung
      histoarchitecture. The zinc supplementation period is brief (only 10 days), but
      it is enough to inhibit some proinflammatory factors. Perhaps, zinc deficiency
      implications must be taken into account in health interventions because
      inflammation and prooxidant environment are associated with ZD in lung.

PMID- 20128681
TI  - Hypoxia and kinase activity regulate lung epithelial cell glutathione.
AB  - The authors investigated the mechanisms by which hypoxia regulates glutathione
      (GSH) in lung epithelial cells, and specifically whether the mitogen-activated
      protein kinase (MAPK) system is involved in the response to hypoxia. Hypoxia
      decreased cellular GSH content and appeared to decrease the effect of N
      acetylcysteine on repletion of GSH after hypoxia. Hypoxia decreased 2 key enzyme
      activities that regulate GSH synthesis, glutamate cysteine ligase (GCL) (E.C.
      6.3.2.2) and glutathione synthase (GS) (E.C. 6.3.2.3). No hypoxia-dependent
      change occurred in GCL or GS protein expression on Western blots. When epithelial
      cells were transfected with an adenoviral vector that caused over expression of
      human catalase protein (Ad.Cat or Ad.mCat), GCL and GS activities did not
      decrease in hypoxia. Inhibition of p38(MAPK) (using SB203580) or extracellular
      signal-regulated kinase (ERK; PD98059) prevented the hypoxia-dependent decrease
      in GCL and GS activity. To seek in vivo correlation, the authors assayed total
      glutathione in lungs and livers from MK2(-/-) (homozygous knockout) mice. MK2(-/
      ) mice are presumably unable to phosphorylate heat shock protein 27 (Hsp27)
      normally, because of absent kinase (MK2) activity. Liver GSH content (expressed
      per mg protein) was 20% less in MK2(-/-) mice than in nontransgenic Black 6
      controls. Down-regulation of lung GSH content in hypoxia depends on peroxide tone
      of the cell and the p38(MAPK) system.

PMID- 20128682
TI  - Progressive endothelial cell damage in an inflammatory model of pulmonary
      hypertension.
AB  - Monocrotaline (MCT)-induces progressive disruption of endothelial cell membrane
      and caveolin-1 leading to pulmonary arterial hypertension (PAH). Treatment
      instituted early rescues caveolin-1 and attenuates PAH. To test the hypothesis
      that the poor response to therapy in established PAH is due to progressive
      deregulation of multiple signaling pathways, the authors investigated time
      dependent changes in the expression of caveolin-1, gp130, PY-STAT3, Bcl-xL, and
      the molecules involved in NO signaling pathway (endothelial nitric oxide synthase
      [eNOS], heat sock protein 90 [HSP90], Akt, soluble guanylate cyclase [sGC] alpha1
      and beta1 subunits). PAH and right ventricular hypertrophy (RVH) were observed at
      2 and 3 weeks. Progressive loss of endothelial caveolin-1 and sGC (alpha1,
      beta1), PY-STAT3 activation, and Bcl-xL expression were observed at 1 to 3 weeks
      post-MCT. The expression of gp130 increased at 48 hours and 1 week, with a
      subsequent loss at 2 and 3 weeks. The expression of eNOS increased at 48 hours
      and 1 week post-MCT, with a significant loss at 3 weeks. The expression of HSP90
      and Akt decreased at 2 and 3 weeks post-MCT concomitant with PAH. Thus, MCT
      induces progressive loss of membrane and cytosolic proteins, resulting in the
      activation of proliferative and antiapoptotic factors, and deregulation of NO
      signaling leading to PAH. An attractive therapeutic approach to treat PAH may be
      an attempt to rescue endothelial cell membrane integrity.

PMID- 20128683
TI  - Anthracyclines in the treatment of early-stage breast cancer: ally or adversary?

PMID- 20128684
TI  - Analyzing the protease web in skin: meprin metalloproteases are activated
      specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby
      triggering its activation.
AB  - The metalloproteases meprin alpha and beta are expressed in several tissues,
      leukocytes, and cancer cells. In skin, meprins are located in separate layers of
      human epidermis indicating distinct physiological functions, supported by effects
      on cultured keratinocytes. Meprin beta induces a dramatic change in cell
      morphology and a significant reduction in cell number, whereas in vitro evidence
      suggests a role for meprin alpha in basal keratinocyte proliferation. Meprins are
      secreted as zymogens that are activated by tryptic proteolytical processing.
      Here, we identify human kallikrein-related peptidases (KLKs) 4, 5, and 8 to be
      specific activators of meprins. KLK5 is capable of activating both
      metalloproteases. Interestingly, KLK4 and 8 cleave off the propeptide of meprin
      beta only, whereas in contrast plasmin exclusively transforms meprin alpha to its
      mature form. Moreover, we show that proKLK7 is processed by meprins. N-terminal
      sequencing revealed cleavage by meprin beta two amino acids N-terminal to mature
      KLK7. Interestingly, this triggering led to an accelerated activation of the
      serine protease in the presence of trypsin, but not of other tryptic KLKs, such
      as KLK2, 4, 5, 8, or 11. In summary, we demonstrate a specific interaction
      between meprin metalloproteases and kallikrein-related peptidases, revealing
      possible interactions within the proteolytic web.

PMID- 20128686
TI  - Immunohistochemical analysis of kallikrein-related peptidases in the normal
      kidney and renal tumors: potential clinical implications.
AB  - Kallikrein-related peptidases (KLKs) have been shown to be differentially
      expressed in various malignancies and shown to be useful tumor markers. Previous
      immunohistochemistry (IHC) analysis demonstrated that KLKs 5, 6, 10, and 11 have
      a potential prognostic significance in renal cell carcinoma (RCC). To further
      explore the significance of KLKs, we examined KLKs 1, 6, 7, and 15 in different
      subtypes of renal tumors. KLK1 has stronger expression in high grade compared to
      low grade clear cell RCC. However, KLK6 and KLK7 show strong expression in low
      grade in contrast to high grade clear cell RCC. Furthermore, the expression of
      KLK7 can distinguish between oncocytoma and chromophobe RCC. Oncocytoma showed
      diffuse, strong granular cytoplasmic staining, but chromophobe RCC showed focal
      weak homogeneous cytoplasmic stain. The pattern of staining of different KLKs can
      also be helpful in differentiating some of the subtypes of renal tumors. Our
      results show the potential ability of KLKs to serve as diagnostic markers and
      expand previous data about the prognostic significance of KLKs in kidney cancer.
      In addition, our study is the first to show the ability of KLK staining to
      distinguish various types of kidney cancers when morphology is similar.

PMID- 20128687
TI  - Glycome profiling using modern glycomics technology: technical aspects and
      applications.
AB  - Glycomics research has become indispensable in many research fields such as
      immunity, signal transduction and development. Moreover, changes in the
      glycosylation of proteins and lipids have been reported in several diseases
      including cancer. The analysis of a complex post-translational modification such
      as glycosylation depends on the availability or development of appropriate
      analytical technologies. The research goal determines the sensitivity, resolution
      and throughput requirements and guides the choice of a particular technology.
      This review highlights the evolution of glycan profiling tools in the past 5
      years. We focus on capillary electrophoresis, liquid chromatography, mass
      spectrometry and lectin microarrays.

PMID- 20128685
TI  - Functional intersection of the kallikrein-related peptidases (KLKs) and
      thrombostasis axis.
AB  - A large body of emerging evidence indicates a functional interaction between the
      kallikrein-related peptidases (KLKs) and proteases of the thrombostasis axis.
      These interactions appear relevant for both normal health as well as pathologies
      associated with inflammation, tissue injury, and remodeling. Regulatory
      interactions between the KLKs and thrombostasis proteases could impact several
      serious human diseases, including neurodegeneration and cancer. The emerging
      network of specific interactions between these two protease families appears to
      be complex, and much work remains to elucidate it. Complete understanding how
      this functional network resolves over time, given specific initial conditions,
      and how it might be controllably manipulated, will probably contribute to the
      emergence of novel diagnostics and therapeutic agents for major diseases.

PMID- 20128688
TI  - Identification of novel peptide inhibitors for human trypsins.
AB  - Human trypsin isoenzymes share extensive sequence similarity, but certain
      differences in their activity and susceptibility to inhibitors have been
      observed. Using phage display technology, we identified seven different peptides
      that bind to and inhibit the activity of trypsin-3, a minor trypsin isoform
      expressed in pancreas and brain. All of the peptides contain at least two of the
      amino acids tryptophan, alanine and arginine, whereas proline was found closer to
      the N-terminus in all but one peptide. All peptides contain two or more
      cysteines, suggesting a cyclic structure. However, we were able to make synthetic
      linear variants of these peptides without losing bioactivity. Alanine replacement
      experiments for one of the peptides suggest that the IPXXWFR motif is important
      for activity. By molecular modeling the same amino acids were found to interact
      with trypsin-3. The peptides also inhibit trypsin-1, but only weakly, if at all,
      trypsin-2 and -C. As trypsin is a highly active enzyme which can activate
      protease-activated receptors and enzymes that participate in proteolytic cascades
      involved in tumor invasion and metastasis, these peptides might be useful lead
      molecules for the development of drugs for diseases associated with increased
      trypsin activity.

PMID- 20128689
TI  - Signal transduction by the atopy-associated human thymic stromal lymphopoietin
      (TSLP) receptor depends on Janus kinase function.
AB  - Thymic stromal lymphopoietin (TSLP) is an interleukin-(IL)-7-like cytokine with
      emerging pathological importance for the development of atopic diseases such as
      allergic asthma bronchiale. The TSLP receptor (TSLPR), a heterodimeric type I
      cytokine receptor, shares the IL-7R alpha-subunit with the IL-7 receptor system.
      The specific TSLPR alpha-chain shows similarities with the gammac receptor chain,
      but has some unusual features within the receptor family in both its ligand
      binding and cytoplasmic domain. The murine TSLPR signals via the signal
      transducers and activators of transcription STAT5 and STAT3, but is unique among
      cytokine receptors in that it activates STATs without the involvement of Janus
      (JAK) tyrosine kinases, but instead utilizes the Src type kinase Tec. Here, we
      show by Western blotting and reporter gene experiments in combination with the
      application of a specific JAK inhibitor that the human TSLP receptor, in
      contrast, requires the function of JAK1 and JAK2 for STAT activation. Moreover,
      we demonstrate that the human TSLPR mediates gene regulation not only through
      STAT5 and STAT3 but has also the potential to mediate transcription via STAT1.
      Our work should help to understand more thoroughly how TSLP triggers inflammatory
      responses in the course of atopic diseases.

PMID- 20128690
TI  - MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway.
AB  - A central point of regulation in the Wnt/beta-catenin signalling pathway is the
      formation of the beta-catenin destruction complex. Axin1, an essential negative
      regulator of Wnt signalling, serves as a scaffold within this complex and is
      critical for rapid turnover of beta-catenin. To examine the mechanism by which
      Wnt signalling disables the destruction complex, we used an immunoprecipitation
      coupled proteomics approach to identify novel endogenous binding partners of
      Axin1. We found mitogen-activated protein kinase kinase kinase 1 (MAP3K1) as an
      Axin1 interactor in Ls174T colorectal cancer (CRC) cells. Importantly,
      confirmation of this interaction in HEK293T cells indicated that the Axin1-MAP3K1
      interaction is induced and modulated by Wnt stimulation. siRNA depletion of
      MAP3K1 specifically abrogated TCF/LEF-driven transcription and Wnt3A-driven
      endogenous gene expression in both HEK293T as well as DLD-1 CRC. Expression of
      ubiquitin ligase mutants of MAP3K1 abrogated TCF/LEF transcription, whereas
      kinase mutants had no effect in TCF-driven activity, highlighting the essential
      role of the MAP3K1 E3 ubiquitin ligase activity in regulation of the Wnt/beta
      catenin pathway. These results suggest that MAP3K1, previously reported as an
      Axin1 inter-actor in c-Jun NH(2)-terminal kinase pathway, is also involved in the
      canonical Wnt signalling pathway and positively regulates expression of Wnt
      target genes.

PMID- 20128691
TI  - Analysis of the DNA-binding activity of p53 mutants using functional protein
      microarrays and its relationship to transcriptional activation.
AB  - Sequence-specific DNA binding is the key function through which tumor suppressor
      p53 exerts transactivation of the downstream target genes, often being impaired
      in cancer cells by mutations in the TP53 gene. Functional protein microarray
      technology enables a high-throughput parallel analysis of protein properties
      within one experiment under the same conditions. Using an array approach, we
      analyzed the DNA binding activity of wild type p53 protein and of 49 variants.
      Our results show significant differences in the binding properties between the
      p53 mutants. The C-terminal mutant R337C displayed the highest DNA binding
      activity on the array. However, the same mutant showed only a partial activation
      in the reporter gene assay and almost no activation of downstream target genes
      after transfection of expression vector into cells lacking endogenous p53. These
      observations demonstrate that DNA binding itself is not sufficient for activating
      the p53 target genes in at least some of the p53 mutants and, therefore, in vitro
      studies might not always reflect in vivo conditions.

PMID- 20128692
TI  - KLK5 gene expression is severely upregulated in androgen-independent prostate
      cancer cells after treatment with the chemotherapeutic agents docetaxel and
      mitoxantrone.
AB  - Kallikrein-related peptidases (KLKs), including KLK5, have been proposed as
      promising biomarkers for prostate cancer diagnosis and prognosis. In the present
      study, we report that distinct augmentations (up to 6.4-fold) of KLK5 mRNA
      expressional levels, calculated via quantitative real-time PCR, occur after
      treatment of DU145 cells with appropriate concentrations, determined by the MTT
      method, of docetaxel and mitoxantrone. Our data reveal the endogenous need of
      prostate cancer cells for modified KLK5 expression to cope with the
      administration of chemotherapeutic drugs. Furthermore, it is proposed that the
      expression profile of KLK5 could serve as a putative biomarker for monitoring the
      treatment response in hormone refractory prostate cancer patients.

PMID- 20128693
TI  - PAMDB, a multilocus sequence typing and analysis database and website for plant
      associated microbes.
AB  - Although there are adequate DNA sequence differences among plant-associated and
      plant-pathogenic bacteria to facilitate molecular approaches for their
      identification, identification at a taxonomic level that is predictive of their
      phenotype is a challenge. The problem is the absence of a taxonomy that describes
      genetic variation at a biologically relevant resolution and of a database
      containing reference strains for comparison. Moreover, molecular evolution,
      population genetics, ecology, and epidemiology of many plant-pathogenic and plant
      associated bacteria are still poorly understood. To address these challenges, a
      database with web interface was specifically designed for plant-associated and
      plant-pathogenic microorganisms. The Plant-Associated Microbes Database (PAMDB)
      comprises, thus far, data from multilocus sequence typing and analysis
      (MLST/MLSA) studies of Acidovorax citrulli, Pseudomonas syringae, Ralstonia
      solanacearum, and Xanthomonas spp. Using data deposited in PAMDB, a robust
      phylogeny of Xanthomonas axonopodis and related bacteria has been inferred, and
      the diversity existing in the Xanthomonas genus and in described Xanthomonas spp.
      has been compared with the diversity in P. syringae and R. solanacearum.
      Moreover, we show how PAMDB makes it easy to distinguish between different
      pathogens that cause almost identical diseases. The scalable design of PAMDB will
      make it easy to add more plant pathogens in the future.

PMID- 20128694
TI  - Distinguishing Heterodera filipjevi and H. avenae using polymerase chain reaction
      restriction fragment length polymorphism and cyst morphology.
AB  - The cereal cyst nematodes Heterodera filipjevi and H. avenae impede wheat
      production in the Pacific Northwest (PNW). Accurate identification of cyst
      nematode species and awareness of high population density in affected fields are
      essential for designing effective control measures. Morphological methods for
      differentiating these species are laborious. These species were differentiated
      using polymerase chain reaction restriction fragment length polymorphism (PCR
      RFLP) of internal transcribed spacer (ITS)-ribosomal (r)DNA with up to six
      restriction endonucleases (TaqI, HinfI, PstI, HaeIII, RsaI, and AluI). The method
      was validated by inspecting underbridge structures of cyst vulval cones. Grid
      soil sampling of an Oregon field infested by both species revealed that H.
      filipjevi was present at most of the infested grid sites but mixtures of H.
      avenae and H. filipjevi also occurred. These procedures also detected and
      differentiated H. filipjevi and H. avenae in soil samples from nearby fields in
      Oregon and H. avenae in samples from Idaho and Washington. Intraspecific
      polymorphism was not observed within H. filipjevi or PNW H. avenae populations
      based on the ITS-rDNA. However, intraspecific variation was observed between H.
      avenae populations occurring in the PNW and France. Methods described here will
      improve detection and identification efficiencies for cereal cyst nematodes in
      wheat fields.

PMID- 20128695
TI  - Tomato plants transformed with the inhibitor-of-virus-replication gene are
      partially resistant to Botrytis cinerea.
AB  - Tomato plants transformed with a cDNA clone encoding the inhibitor-of-virus
      replication (IVR) gene were partially resistant to Botrytis cinerea. This
      resistance was observed as a significant reduction in the size of lesions induced
      by the fungus in transgenic plants compared with the lesions on the nontransgenic
      control plants. This resistance was weakened when plants were kept at an elevated
      temperature, 32 degrees C, before inoculation with B. cinerea compared with
      plants kept at 17 to 22 degrees C prior to inoculation. Resistance correlated
      with the presence of IVR transcripts, as detected by reverse transcription
      polymerase chain reaction. This is one of the few cases in which a gene
      associated with resistance to a virus also seems to be involved in resistance to
      a fungal disease.

PMID- 20128696
TI  - Wheat cultivar-specific disease synergism and alteration of virus accumulation
      during co-infection with Wheat streak mosaic virus and Triticum mosaic virus.
AB  - Triticum mosaic virus (TriMV), the type member of the newly proposed Poacevirus
      genus, and Wheat streak mosaic virus (WSMV), the type member of Tritimovirus
      genus of the family Potyviridae, infect wheat naturally in the Great Plains and
      are transmitted by wheat curl mites. In this study, we examined the ability of
      these viruses to infect selected cereal hosts, and found several differential
      hosts between TriMV and WSMV. Additionally, we examined the interaction between
      WSMV and TriMV in three wheat cultivars at two temperature regimens (19 and 20 to
      26 degrees C), and quantified the virus concentration in single and double
      infections by real-time reverse-transcription polymerase chain reaction. Double
      infections in wheat cvs. Arapahoe and Tomahawk at both temperature regimens
      induced disease synergism with severe leaf deformation, bleaching, and stunting,
      with a 2.2- to 7.4-fold increase in accumulation of both viruses over single
      infections at 14 days postinoculation (dpi). However, at 28 dpi, in double
      infections at 20 to 26 degrees C, TriMV concentration was increased by 1.4- to
      1.8-fold in Arapahoe and Tomahawk but WSMV concentration was decreased to 0.5
      fold. WSMV or TriMV replicated poorly in Mace at 19 degrees C with no synergistic
      interaction whereas both viruses accumulated at moderate levels at 20 to 26
      degrees C and induced mild to moderate disease synergism in doubly infected Mace
      compared with Arapahoe and Tomahawk. Co-infections in Mace at 20 to 26 degrees C
      caused increased TriMV accumulation at 14 and 28 dpi by 2.6- and 1.4-fold and
      WSMV accumulated at 0.5- and 1.6-fold over single infections, respectively. Our
      data suggest that WSMV and TriMV induced cultivar-specific disease synergism in
      Arapahoe, Tomahawk, and Mace, and these findings could have several implications
      for management of wheat viruses in the Great Plains.

PMID- 20128697
TI  - Screening molecules for control of citrus huanglongbing using an optimized
      regeneration system for 'Candidatus Liberibacter asiaticus'-infected periwinkle
      (Catharanthus roseus) cuttings.
AB  - Citrus huanglongbing is one of the most destructive diseases of citrus worldwide.
      The disease is associated with three different species of 'Candidatus
      Liberibacter', of which 'Ca. L. asiaticus' is the most widely distributed. An
      optimized system using 'Ca. L. asiaticus'-infected periwinkle cuttings was
      developed to screen chemical compounds effective for controlling the bacterial
      population while simultaneously assessing their phytotoxicity. The optimal
      regeneration conditions were determined to be the use of vermiculite as a growth
      medium for the cuttings, and a fertilization routine using half-strength
      Murashige and Tucker medium supplemented with both naphthalene acetic acid (4
      microg/ml) and indole-3-butyric acid (4 microg/ml). This system allowed a plant
      regeneration rate of 60.6% for 'Ca. L. asiaticus'-infected cuttings in contrast
      to the <1% regeneration rate with water alone. Two chemical agents, penicillin G
      sodium and 2,2-dibromo-3-nitrilopropionamide (DBNPA), were found to be effective
      at eliminating or suppressing the 'Ca. L. asiaticus' bacterium in this periwinkle
      regeneration system. When treated with penicillin G sodium at 50 microg/ml, all
      plants regenerated from 'Ca. L. asiaticus'-infected cuttings were 'Ca. L.
      asiaticus' negative as determined by both nested polymerase chain reaction (PCR)
      and quantitative real-time PCR. In addition, DBNPA was also able to significantly
      reduce the percentage of 'Ca. L. asiaticus'-positive plants and the titer of the
      'Ca. L. asiaticus' bacterium at 200 microl/liter.

PMID- 20128698
TI  - Initiation, development, and survival of cleistothecia of Podosphaera aphanis and
      their role in the epidemiology of strawberry powdery mildew.
AB  - A collection of four clonal isolates of Podosphaera aphanis was heterothallic and
      was composed of two mutually exclusive mating types. Cleistothecial initials
      approximately 20 to 30 microm in diameter were observed within 7 to 14 days after
      pairing of compatible isolates and developed into morphologically mature
      ascocarps within 4 weeks after initiation on both potted plants maintained in
      isolation and in field plantings in New York State and southern Norway.
      Ascospores progressed through a lengthy maturation process over winter, during
      which (i) the conspicuous epiplasm of the ascus was absorbed; (ii) the osmotic
      potential of the ascospore cytoplasm increased, resulting in bursting of
      prematurely freed spores in water; and, finally, (iii) resulting in the
      development of physiologically mature, germinable, and infectious ascospores.
      Release of overwintered ascospores from field collections was coincident with
      renewed plant growth in spring. Overwintered cleistothecia readily dehisced when
      wetted and released ascospores onto glass slides, detached strawberry leaves, and
      leaves of potted plants. Plant material exposed to discharged ascospores
      developed macroscopically visible mildew colonies within 7 to 10 days while
      noninoculated controls remained mildew free. Scanning electron and light
      microscopy revealed that cleistothecia of P. aphanis were enmeshed within a dense
      mat of hyphae on the persistent leaves of field-grown strawberry plants and were
      highly resistant to removal by rain while these leaves remained alive. In
      contrast, morphologically mature cleistothecia on leaves of nine deciduous
      perennial plant species were readily detached by simulated rain and seemed
      adapted for passive dispersal by rain to other substrates. Contrary to many
      previous reports, cleistothecia appear to be a functional source of primary
      inoculum for strawberry powdery mildew. Furthermore, they differ substantially
      from cleistothecia of powdery mildews of many deciduous perennial plants in their
      propensity to remain attached to the persistent leaves of their host during the
      intercrop period.

PMID- 20128699
TI  - Sequential expression of bacterial virulence and plant defense genes during
      infection of tomato with Clavibacter michiganensis subsp. michiganensis.
AB  - The molecular interactions between Clavibacter michiganensis subsp. michiganensis
      and tomato plant were studied by following the expression of bacterial virulence
      and host-defense genes during early stages of infection. The C. michiganensis
      subsp. michiganensis genes included the plasmid-borne cellulase (celA) and the
      serine protease (pat-1), and the serine proteases chpC and ppaA, residing on the
      chp/tomA pathogenicity island (PAI). Gene expression was measured following
      tomato inoculation with Cmm382 (wild type), Cmm100 (lacking the plasmids pCM1 and
      pCM2), and Cmm27 (lacking the PAI). Transcriptional analysis revealed that celA
      and pat-1 were significantly induced in Cmm382 at initial 12 to 72 h, whereas
      chpC and ppaA were highly expressed only 96 h after inoculation. Interdependence
      between the expression of chromosomal and of plasmid-located genes was revealed:
      expression of celA and pat-1 was substantially reduced in the absence of the
      chp/tomA PAI, whereas chpC and ppaA expressions were reduced in the absence of
      the virulence plasmids. Transcription of chromosomal genes involved in cell wall
      degradation (i.e., pelA1, celB, xysA, and xysB), was also induced at early stages
      of infection. Expression of the host-defense genes, chitinase class II and
      pathogenesis-related protein-5 isoform was induced in the absence of the PAI at
      early stages of infection, suggesting that PAI-located genes are involved in
      suppression of tomato basal defenses.

PMID- 20128700
TI  - Xanthomonas oryzae pv. oryzae XKK.12 contains an AroQgamma chorismate mutase that
      is involved in rice virulence.
AB  - Chorismate mutase (CM) is a key enzyme in the shikimate pathway which is
      responsible for the synthesis of aromatic amino acids. There are two classes of
      CMs, AroQ and AroH, and several pathogenic bacteria have been reported to possess
      a subgroup of CMs designated AroQ(gamma). These CMs are usually exported to the
      periplasm or outside the cell; in a few cases, they have been reported to be
      involved in virulence and their precise role is currently unknown. Here, we
      report that the important rice pathogen Xanthomonas oryzae pv. oryzae XKK.12
      produces an AroQ(gamma) CM which we have purified and characterized from spent
      supernatants. This enzyme is synthesized in planta and X. oryzae pv. oryzae knock
      out mutants are hypervirulent to rice. The role of this enzyme in X. oryzae pv.
      oryzae rice virulence is discussed.

PMID- 20128701
TI  - Vegetative compatibility groups in Colletotrichum coccodes subpopulations from
      Australia and genetic links with subpopulations from Europe/Israel and North
      America.
AB  - Vegetative compatibility of 94 isolates of Colletotrichum coccodes from Australia
      originating from potato, soil, and a weed (Solanum esuriale) was tested using
      nitrate-nonutilizing (nit) mutants. Isolates distributed to six vegetative
      compatibility groups (VCGs), five of them multimember (24.5, 23.4, 13.8, 12.8,
      and 7.5% distribution) and only one composed of two isolates (2.1%); 15.9% of
      them were not assigned to any of the VCGs. Aggressiveness of 51 isolates
      representing all six VCGs was tested by mature green tomato bioassay: isolates
      assigned to AUS-VCG-4 were the most aggressive and those in AUS-VCG-3 the least
      (P < 0.05). Isolates from warmer climates and lower latitudes were more
      aggressive (P < 0.05). In addition, we report for the first time complementations
      between isolates from Australia (AUS); North America (NA); and Israel, The
      Netherlands, Scotland, France, Germany (EU/I). Isolates assigned to AUS-VCG-4
      anastomosed with isolates assigned to EU/I-VCG-7 and NA-VCG-5 (which also
      anastomosed with each other). Isolates assigned to EU/I-VCG-6 anastomosed with
      isolates assigned to NA-VCG-2 and isolates assigned to AUS-VCG-2 anastomosed with
      isolates assigned to EU/I-VCG-2. The linkage between subpopulations could result
      from the limited exchange of seed tubers among continents, or could be due to,
      for instance, gene flow, selection, or a limited number of polymorphic vegetative
      incompatibility genes.

PMID- 20128702
TI  - H-gene-mediated resistance to Hessian fly exhibits features of penetration
      resistance to fungi.
AB  - Features shared by host-specific phytophagous insects and biotrophic plant
      pathogens include gene-for-gene interactions and the ability to induce
      susceptibility in plants. The Hessian fly shows both. To protect against Hessian
      fly, grasses have H genes. Avirulent larvae die on H-gene-containing resistant
      plants but the cause of death is not known. Imaging techniques were used to
      examine epidermal cells at larval attack sites, comparing four resistant wheat
      genotypes (H6, H9, H13, and H26) to a susceptible genotype. Present in both
      resistant and susceptible plants attacked by larvae were small holes in the
      tangential cell wall, with the size of the holes (0.1 microm in diameter)
      matching that of the larval mandible. Absent from attacked resistant plants were
      signs of induced susceptibility, including nutritive tissue and ruptured cell
      walls. Present in attacked resistant plants were signs of induced resistance,
      including cell death and fortification of the cell wall. Both presumably limit
      larval access to food, because the larva feeds on the leaf surface by sucking up
      liquids released from ruptured cells. Resistance was associated with several
      subcellular responses, including elaboration of the endoplasmic reticulum-Golgi
      complex and associated vesicles. Similar responses are observed in plant
      resistance to fungi, suggesting that "vesicle-associated penetration resistance"
      also functions against insects.

PMID- 20128703
TI  - Trichothecene mycotoxins associated with potato dry rot caused by Fusarium
      graminearum.
AB  - Fusarium graminearum, a known producer of trichothecene mycotoxins in cereal
      hosts, has been recently documented as a cause of dry rot of potato tubers in the
      United States. Due to the uncertainty of trichothecene production in these
      tubers, a study was conducted to determine the accumulation and diffusion of
      trichothecenes in potato tubers affected with dry rot caused by F. graminearum.
      Potato tubers of cv. Russet Burbank were inoculated with 14 F. graminearum
      isolates from potato, sugar beet, and wheat and incubated at 10 to 12 degrees C
      for 5 weeks to determine accumulation of trichothecenes in potato tubers during
      storage. Twelve of the isolates were classified as deoxynivalenol (DON) genotype
      and two isolates were as nivalenol (NIV) genotype. Trichothecenes were detected
      only in rotted tissue. DON was detected in all F. graminearum DON genotype
      isolates up to 39.68 microg/ml in rotted potato tissue. Similarly, both NIV
      genotype isolates accumulated NIV in rotted potato tissue up to 18.28 microg/ml.
      Interestingly, isolates classified as genotype DON accumulated both DON and NIV
      in the dry rot lesion. Potato tubers were then inoculated with two isolates of F.
      graminearum chemotype DON and incubated up to 7 weeks at 10 to 12 degrees C and
      assayed for DON diffusion. F. graminearum was recovered from >53% of the
      isolations from inoculated tubers at 3 cm distal to the rotted tissue after 7
      weeks of incubation but DON was not detected in the surrounding tissue. Based in
      this data, the accumulation of trichothecenes in the asymptomatic tissue
      surrounding dry rot lesions caused by F. graminearum is minimal in cv. Russet
      Burbank potato tubers stored for 7 weeks at customary processing storage
      temperatures.

PMID- 20128704
TI  - Effect of crew size on objective measures of resuscitation for out-of-hospital
      cardiac arrest.
AB  - BACKGROUND: There is no consensus among emergency medical services (EMS) systems
      as to the optimal numbers and training of EMS providers who respond to the scene
      of prehospital cardiac arrests. Increased numbers of providers may improve the
      performance of cardiopulmonary resuscitation (CPR), but this has not been studied
      as part of a comprehensive resuscitation scenario. OBJECTIVE: To compare
      different all-paramedic crew size configurations on objective measures of patient
      resuscitation using a high-fidelity human simulator. METHODS: We compared two-,
      three-, and four-person all-paramedic crew configurations in the effectiveness
      and timeliness of performing basic life support (BLS) and advanced life support
      (ALS) skills during the first 8 minutes of a simulated cardiac arrest scenario.
      Crews were compared to determine differences in no-flow fraction (NFF) as a
      measure of effectiveness of CPR and time to defibrillation, endotracheal
      intubation, establishment of intravenous access, and medication administration.
      RESULTS: There was no significant difference in mean NFF among the two-, three-,
      and four-provider crew configurations (0.32, 0.26, and 0.27, respectively; p =
      0.105). More three- and four-person groups completed ALS procedures during the
      scenario, but there was no significant difference in time to performance of BLS
      or ALS procedures among the crew size configurations for completed procedures.
      There was a trend toward lower time to intubation with increasing group size,
      though this was not significant using a Bonferroni-corrected p-value of 0.01
      (379, 316, and 263 seconds, respectively; p = 0.018). CONCLUSION: This study
      found no significant difference in effectiveness of CPR or in time to performance
      of BLS or ALS procedures among crew size configurations, though there was a trend
      toward decreased time to intubation with increased crew size. Effectiveness of
      CPR may be hindered by distractions related to the performance of ALS procedures
      with increasing group size, particularly with an all-paramedic provider model. We
      suggest a renewed emphasis on the provision of effective CPR by designated
      providers independent of any ALS interventions being performed.

PMID- 20128706
TI  - Tyrosine kinase inhibitors to treat liver cancer.
AB  - IMPORTANCE OF THE FIELD: Hepatocellular carcinoma (HCC) is the third most common
      cause of cancer-related death worldwide. Although patients with early-stage
      disease have a good prognosis, there has been no effective therapy available for
      those with advanced disease. Despite the death risk of patients with advanced HCC
      being reduced with sorafenib therapy, many patients eventually turn out to be
      refractory to this therapy. Thus, treatment of HCC remains an urgent health
      concern. AREAS COVERED IN THIS REVIEW: Recent improvement in understanding the
      pathophysiology of HCC at the molecular level has fostered the development of
      molecular targeted therapies that specifically block the disrupted pathways. WHAT
      THE READER WILL GAIN: This review summarizes the preclinical and clinical data
      from 2004 to 2009 on the efficacy and safety of the emerging drug for the
      treatment of HCC, including small molecule inhibitors (erlotinib, sunitinib,
      sorafenib, vandetanib, cediranib, brivanib and dovitinib) and the rationale for
      combination therapies for patients with advanced HCC. TAKE HOME MESSAGE:
      Understanding the mechanisms of action, safety and efficacy of these new agents
      and new methods of combining these drugs may help prolong overall survival of
      patients with HCC and reduce disease recurrence after surgery or ablative
      therapies.

PMID- 20128705
TI  - In-flight automated external defibrillator use and consultation patterns.
AB  - BACKGROUND: Limited information exists about the in-flight use and outcomes
      associated with automated external defibrillators (AEDs) on commercial airlines.
      OBJECTIVE: To describe the characteristics and outcomes of AED use during in
      flight emergencies including in-flight cardiac arrest and the associated ground
      medical consultation patterns. METHODS: We collected cases of AED use that were
      self-reported to an airline consultation service from three U.S. airlines between
      May 2004 and March 2009. We reviewed all available data files, related
      consultation forms, and recordings. For each case, demographics, initial rhythm,
      shock delivery/success, survival to admission, and ground medical consultation
      use were obtained. Success was defined as the return of a perfusing rhythm.
      Initial rhythms were classified as sinus, heart block, supraventricular
      tachycardia (SVT), atrial fibrillation/flutter, asystole, pulseless electrical
      activity (PEA), and ventricular fibrillation (VF)/ventricular tachycardia (VT).
      RESULTS: There were a total of 169 AED applications with 40 cardiac arrests. The
      mean patient ages were 58 years (standard deviation [SD] 15) and 63 years (SD
      12), respectively; both populations were 64% male. AEDs were applied for
      monitoring in 129 (76%) cases with the following initial rhythms: sinus, 114
      (88%); atrial fibrillation/flutter, seven (5%); complete heart block, four (3%);
      and SVT, four (3%). Presenting rhythms among the cardiac arrest population were
      as follows: asystole, 16 (40%); VF/VT, 10 (25%); and PEA, 14 (35%). Fourteen
      patients were defibrillated, including nine of the 10 patients with initial VF/VT
      and five for the presence of VF/VT after resuscitation for initial PEA/asystole.
      Defibrillation was advised but not performed in the remaining case of initial
      VF/VT, and no medical consultation was obtained. All five successful
      defibrillations occurred in patients with initial VF/VT. There were six (15%; 95%
      confidence interval [CI] 3-27%) survivors, with five survivals occurring after
      successful defibrillation for initial VF/VT and one with return of a perfusing
      rhythm after cardiopulmonary resuscitation (CPR) for a junctional rhythm.
      Survival in those with VF/VT was five of 10 (50%; 95% CI 14-86%). Medications
      were delivered in two cases. The median time to first shock was 19 seconds
      (interquartile range [IQR] 12-24 seconds) after AED application. Medical
      consultation was obtained in 42 (33%) of the 129 AED monitoring cases and 14
      (35%) of the 40 cardiac arrest cases. CONCLUSION: Use of AEDs resulted in 50%
      survival among those with VF/VT in flight and 15% overall survival for cardiac
      arrest. Survival is poor among patients presenting with nonshockable rhythms.
      AEDs are used extensively for in-flight monitoring, with significant rhythms
      identified. Ground medical consultation is sought in only one-third of AED uses
      and cardiac arrests.

PMID- 20128707
TI  - RNA as performance-enhancers for dendritic cells.
AB  - IMPORTANCE OF THE FIELD: Although studies have demonstrated that antigen-loaded
      dendritic cells (DC) elicit antigen-specific immune responses, the clinical
      benefit from DC-based cancer immunotherapy remains low. RNA, in the form of mRNA,
      has not only been used as a source of antigen but more recently as a way to
      stimulate DC to produce immunostimulatory molecules. As siRNA it has allowed
      researchers to modify DC to produce a favorable cytokine profile or to present
      antigen that may generate the desired immune response. AREAS COVERED IN THIS
      REVIEW: When loading DC with RNA that encodes immunostimulatory protein, rather
      than a source of antigen, optimal translation and efficient transfection into DC
      are critical. Studies addressing these issues and the functional consequences of
      modulating DC function are reviewed. WHAT THE READER WILL GAIN: RNA can be used
      to load DC with antigen and to encode proteins that will enhance the immune
      response. Co-transfection with multiple mRNAs or mRNA plus siRNA can
      significantly improve vaccine efficacy. TAKE HOME MESSAGE: One conclusion from
      Phase I clinical trials with DC loaded with tumor antigen is that tumor-specific
      induction of immune responses is not sufficient to destroy pre-established
      tumors. The advantage of transfection with mRNA is the ability to load DC with
      antigen-encoding mRNA and immunostimulatory protein-encoding mRNA to achieve the
      desired clinical response.

PMID- 20128708
TI  - Targeting chronic inflammation in cerebral aneurysms: focusing on NF-kappaB as a
      putative target of medical therapy.
AB  - IMPORTANCE OF THE FIELD: Cerebral aneurysms (CAs) are the main cause of life
      threatening subarachnoid hemorrhage. Given its prevalence and endpoint, CA
      treatment is a public health issue. Effective medical treatment of CAs is lacking
      because the detailed mechanisms of CA formation are incompletely understood.
      AREAS COVERED IN THIS REVIEW: The aim of this contribution is to review recent
      articles about CA formation, to suggest the underlying mechanisms of CA
      formation, and to discuss potential therapeutic targets for treatment. Articles
      were collected by an internet search of PubMed using the keywords 'intracranial'
      or 'cerebral aneurysm'. WHAT THE READERS WILL GAIN: A review of articles about
      the pathogenesis of CA formation focusing on inflammation. Recent articles
      demonstrate that inflammation-related-molecule induction and inflammatory cell
      infiltration in CA walls and the close relationship between inflammatory
      responses and CA formation. From studies in experimental models, chronic
      inflammation triggered primarily by NF-kappaB activation in endothelial cells and
      subsequent macrophage infiltration have critical roles in CA formation.
      Inhibition of inflammation-related molecules in CA walls results in the decreased
      incidence of CA formation. TAKE-HOME MESSAGE: Agents with anti-inflammatory
      activity (particularly anti- NF-kappaB effects) have potential as therapeutic
      drugs for CAs.

PMID- 20128709
TI  - EUROPREV asks patients about preventive services.

PMID- 20128713
TI  - Electroconvulsive therapy: a review of knowledge, experience and attitudes of
      patients concerning the treatment.
AB  - OBJECTIVES: Despite its proven efficacy and safety, electroconvulsive therapy
      (ECT) has a negative image and attracts widespread public criticism. In contrast,
      perceptions of patients who have received ECT appear to be more favourable. This
      review intended to encapsulate the evidence on knowledge and views concerning ECT
      among its recipients. METHODS: Extensive electronic and manual searches were
      conducted to identify all relevant studies on the subject. RESULTS: Seventy-five
      reports were found suitable. The evidence from these studies suggested that
      patients undergoing ECT were usually poorly informed about it. This was
      attributable to factors such as unsatisfactory pre-treatment explanations or post
      ECT memory impairment. About one-third undergoing ECT reported feeling coerced to
      have the treatment. Fear of ECT and distressing side effects were also present in
      a majority. Despite these problems, a vast majority of patients perceived ECT to
      be helpful and had positive views regarding the treatment. Simultaneously, a
      sizeable proportion was quite critical, although little was known about the
      extent and nature of such disapproval. CONCLUSIONS: Overall, the weight of the
      evidence supports the notion that patients undergoing ECT are well-disposed
      towards it. However, much needs to be done to improve the practice of ECT and to
      enhance patients' satisfaction with the experience of treatment.

PMID- 20128714
TI  - From Julius Wagner-Jauregg to biomarkers and immunological therapies.

PMID- 20128715
TI  - Factors associated with weight gain with olanzapine.

PMID- 20128719
TI  - Digital video documentation as evidence of clinical skill acquisition.
AB  - Video recordings have become requirements for the assessment and recording of the
      consulting skills module of the MRCGP examination and surgical skill modules for
      the post FRCS hand diploma examination. Previous research has shown that the
      knowledge and judgement skills needed by trainees to achieve operative competence
      can be reliably assessed using structured checklists. However evaluation of
      surgical competency should also include technical skills, which have been
      difficult to document adequately and transparently. There is now evidence
      demonstrating that surgeons can discriminate between the video recordings of a
      competent and non-competent trainee. Like those of previous researchers our
      findings indicate that intra-operative video monitoring enables an objective and
      permanent recordable assessment of the a trainees skill level whilst completing
      the checklist after a particular procedure. Video evidence can also be
      distributed widely to assessors outside the trainee's locale.

PMID- 20128722
TI  - The Canon MP-E 65MM macro lens.

PMID- 20128723
TI  - Chaperones within a sensitive medical photography environment.

PMID- 20128724
TI  - A review of resources on the internet which can be utilized for medical training.

PMID- 20128725
TI  - Personalising your learning.

PMID- 20128729
TI  - The IMI and HeSCA Awards--a retrospective.

PMID- 20128730
TI  - Genotyping mitochondrial DNA single nucleotide polymorphisms by PCR ligase
      detection reactions.
AB  - BACKGROUND: The identification of human mitochondrial DNA (mtDNA) sequence
      variations, especially single nucleotide polymorphisms (SNPs), is important for
      many applications. The PCR-ligase detection reaction (LDR) method can reduce
      false-positives and eliminate the need for both post-PCR and post-ligation
      purifications in SNP analyses. In addition, it has been successfully employed to
      detect point mutations in various nuclear genes. In this study, we used the PCR
      LDR platform to characterize mtDNA SNPs. METHODS: Multiplex PCR-LDRs were used to
      genotype 19 mtDNA single nucleotide polymorphic sites from 812 samples.
      Performance of the method was assessed by direct sequencing of 44 samples.
      RESULTS: We established an overall 97.4% success rate with 99.2% accuracy using
      the multiplex PCR-LDR methodology. CONCLUSIONS: The PCR-LDR mtDNA genotyping
      technique is simple, highly accurate, has high-throughput, and is cost-effective.
      Therefore, this method is applicable to mtDNA haplotyping in various
      applications.

PMID- 20128731
TI  - Low expression of human beta-defensin 1 in duodenum of celiac patients is
      partially restored by a gluten-free diet.
AB  - BACKGROUND: Human beta-defensins (hBDs) are small cationic, widely expressed
      proteins involved in innate immunity that exert strong bactericidal activity
      toward various pathogens. However, the role of hBDs in various diseases to which
      bacterial infection add severity, as it is in celiac disease (CD), is not yet
      clear. We analyzed the expression of the hBD1, hBD2, hBD3 and hBD4 genes in
      patients with CD during the active phase and after remission following a gluten
      free diet to determine their role in development and relapse of CD. METHODS: We
      studied 21 unrelated adults with CD (confirmed by anti-thyroglobulin antibodies
      and intestinal biopsy); 14 were evaluated at diagnosis, before diet modification,
      and seven after 2 years of a gluten-free diet. Thirty-six unrelated adults served
      as controls. We analyzed the mRNA expression of hBD1, 2, 3 and 4 on biopsy
      samples of duodenum obtained from all patients during endoscopy for diagnostic
      purposes. We used real-time polymerase chain reaction with TaqMan probes and
      obtained gene expression data using the delta-Ct method. RESULTS: hBD1 mRNA was
      significantly lower in patients with active CD compared with patients on diet
      modification, whereas the mRNA levels of the other three defensins did not differ
      significantly between the two subgroups. Interestingly, the gluten-free diet
      restored only partially hBD1 expression as compared to a normal group of celiac
      free subjects. CONCLUSIONS: Our data reinforce the evidence that hBD1 expression
      is greatly reduced in the duodenum of patients with active CD. It also
      strengthens the concept that reduced activity of immune peptides may predispose
      individuals to bacterial proliferation that contributes to the pathogenesis of
      CD.

PMID- 20128732
TI  - Clinical application of a lectin-antibody ELISA to measure fucosylated
      haptoglobin in sera of patients with pancreatic cancer.
AB  - BACKGROUND: Recent advanced techniques in glycobiology have produced a number of
      tumor marker candidates. As a result from the glycomic approach, we found that
      fucosylated haptoglobin in sera was a possible tumor marker for pancreatic cancer
      (PC). Although Aleuria aurantia lectin (AAL) blotting can detect fucosylated
      haptoglobin, it is difficult to quantify fucosylated haptoglobin precisely. To
      overcome this problem, we developed a fucosylated haptoglobin detection kit as a
      sandwich enzyme-linked immune sorbent assay (ELISA) using AAL and the Fab portion
      of anti-haptoglobin antibody. In the present study, we investigated the clinical
      application of this lectin-antibody ELISA kit to measure fucosylated haptoglobin
      in PC. METHODS: We measured fucosylated haptoglobin in patients with PC with a
      lectin-antibody ELISA kit. The fucosylated haptoglobin measured with this assay
      was compared with lectin blotting data, and the discrepancy was analyzed by
      immunoprecipitation methods. The concentration of fucosylated haptoglobin was
      investigated with respect to the clinical stage of PC. We also measured
      fucosylated haptoglobin, using 397 cases of several types of cancers including
      PC, benign diseases, and normal controls. RESULTS: The sensitivity and
      specificity for the differential diagnosis of PC from normal controls was 50% and
      91%, respectively. The results from lectin-antibody ELISA were significantly
      correlated with data from previous AAL blotting studies. Positive rates of
      fucosylated haptoglobin with this method in patients with PC were significantly
      higher in cases of stage IV compared with other clinical stages. Fucosylated
      haptoglobin was increased in several types of cancers, in which fucosylated
      haptoglobin was reported to increase. CONCLUSIONS: While certain cases showed a
      discrepancy in fucosylated haptoglobin concentrations between the lectin-antibody
      ELISA and conventional lectin blotting, this novel type of lectin-antibody ELISA
      might be useful for a tumor marker for PC.

PMID- 20128733
TI  - Assessment of critical values policies in Italian institutions: comparison with
      the US situation.
AB  - BACKGROUND: Critical value reporting is considered an essential tool to ensure
      the quality of medical laboratory services. Important issues include defining cut
      off values, assessing responsibility for communication and adopting information
      technology solutions to improve notification. Here, we report the state of
      critical value reporting in a large cohort of Italian laboratories and comparison
      with Q-Probes surveys from the College of American Pathologists as
      representatives of the US situation. METHODS: To compare critical value policies
      and procedures, formulation of critical values list with critical values limits
      and monitoring tools, a web-based questionnaire was formulated for 389
      institutions participating in the External Quality Assessment Schemes of Veneto
      Region, in Italy. RESULTS: A total of 90 clinical laboratories submitted data.
      Accredited laboratories represented 82.2% of participants, but written procedures
      for reporting were indicated by 70.5% of participants. Relevant differences
      between US and Italian policies have been observed, particularly regarding who
      provides the notification and on the formulation of the cut-off threshold for
      critical values. CONCLUSIONS: Accreditation according to international standards
      can decrease differences regarding the management of critical values across
      laboratories of different countries. However, the issues concerning critical
      limits should be debated and a consensus critical values list should be
      considered. Automated systems could offer improvements regarding some issues,
      such as who makes the notification, reducing the time spent in notification of
      critical values. Surveys for comparing and improving existing policies regarding
      critical values should be promoted at an international level.

PMID- 20128734
TI  - Performance evaluation of the Abbott RealTime HCV Genotype II for hepatitis C
      virus genotyping.
AB  - BACKGROUND: The Abbott RealTime hepatitis C virus (HCV) Genotype II (Abbott
      Molecular Inc.) for HCV genotyping, which uses real-time PCR technology, has
      recently been developed. METHODS: Accuracy and sensitivity of detection were
      assessed using the HCV RNA PHW202 performance panel (SeraCare Life Sciences).
      Consistency with restriction fragment mass polymorphism (RFMP) data, cross
      reactivity with other viruses, and the ability to detect minor strains in
      mixtures of genotypes 1 and 2 were evaluated using clinical samples. RESULTS: All
      performance panel viruses were correctly genotyped at levels of >500 IU/mL.
      Results were 100% concordant with RFMP genotypic data (66/66). However, 5% (3/66)
      of the samples examined displayed probable genotypic cross reactivity. No cross
      reactivity with other viruses was evident. Minor strains in the mixtures were not
      effectively distinguished, even at quantities higher than the detection limit.
      CONCLUSIONS: The Abbott RealTime HCV Genotype II assay was very accurate and
      yielded results consistent with RFMP data. Although the assay has the advantages
      of automation and short turnaround time, we suggest that further improvements are
      necessary before it is used routinely in clinical practice. Efforts are needed to
      decrease cross reactivity among genotypes and to improve the ability to detect
      minor genotypes in mixed infections.

PMID- 20128736
TI  - Quantitative determination of propranolol by ultraviolet HPLC in human plasma.
AB  - Many previous published methods for the quantitative determination of propranolol
      (PRN) in human plasma have poor recoveries and were not validated according to
      the FDA guideline. The aim of this study is to develop a simple HPLC method for
      detecting PRN in human plasma and to validate it so that it can be applied to a
      clinical study. Chromatographic separation was achieved using a mixture of a
      mobile phase consisting of 160 ml water, 180 ml methanol, 70 ml acetonitrile, 2.5
      ml acetic acid, and 125 microl triethylamine (v/v). The pH of the whole mixture
      was adjusted to 3.4. A flow rate of 0.5 ml/min was employed throughout with a 15
      microl injection volume. Detection was done using a UV detector at 291 nm. The
      validated method was linear for concentrations ranging from 15-180 ng/ ml with a
      good separation and specificity for both PRN and its internal standard,
      oxprenolol (OXP), with excellent recoveries, precision, and accuracies. The limit
      of detection (LOD) and limit of quantification (LOQ) were 1 and 10 ng/ml,
      respectively. The stability studies demonstrated that PRN is stable in the
      autosampler vials and also up to 3.5 months. To the authors' knowledge, the
      recovery, that ranged between 97.9-102.7%, is the highest among all previously
      reported methods that used HPLC with UV detection. The developed and validated
      method for PRN analysis is excellent and applicable to a clinical study.

PMID- 20128735
TI  - The effect of membrane domains on the G protein-phospholipase Cbeta signaling
      pathway.
AB  - The plasma membrane serves as a barrier to limit the exit and entry of components
      into and out of the cell, offering protection from the external environment.
      Communication between the cell and the external environment is mediated by
      multiple signaling pathways. While the plasma membrane was historically viewed as
      a lipid bilayer with freely diffusing proteins, the last decade has shown that
      the lipids and proteins in the plasma membrane are organized in a non-random
      manner, and that this organization can direct and modify various signaling
      pathways in the cell. In this review, we qualitatively discuss the ways that
      membrane domains can affect cell signaling. We then focus on how membrane domains
      can affect a specific signaling pathway--the G protein-phospholipase Cbeta
      pathway and show how membrane domains can play an active role in directing or
      redirecting G protein signals.

PMID- 20128741
TI  - P300 Chinese input system based on Bayesian LDA.
AB  - A brain-computer interface (BCI) is a new communication channel between humans
      and computers that translates brain activity into recognizable command and
      control signals. Attended events can evoke P300 potentials in the
      electroencephalogram. Hence, the P300 has been used in BCI systems to spell,
      control cursors or robotic devices, and other tasks. This paper introduces a
      novel P300 BCI to communicate Chinese characters. To improve classification
      accuracy, an optimization algorithm (particle swarm optimization, PSO) is used
      for channel selection (i.e., identifying the best electrode configuration). The
      effects of different electrode configurations on classification accuracy were
      tested by Bayesian linear discriminant analysis offline. The offline results from
      11 subjects show that this new P300 BCI can effectively communicate Chinese
      characters and that the features extracted from the electrodes obtained by PSO
      yield good performance.

PMID- 20128742
TI  - Parameter study on a finite element model of the middle ear.
AB  - Models of the middle ear basing on the finite element method (FEM) have
      contributed to a better understanding of the function of its different
      components. The geometry, the choice of boundary conditions and material
      properties have a crucial influence on the model. The influence of individual
      parameters was investigated. Based on a magnetic resonance imaging data set, a
      finite element model (FEm) of the middle ear was established. The transfer
      function (TF) at a sound pressure level of 90 dB and a frequency range from 100
      Hz to 10 kHz was determined. Altogether, 24 parameters were varied individually
      and the influence on the TF was investigated. The parameter study was based on
      varying the stiffness and damping of each material as well as on anatomic
      variations, such as thickness and anisotropy of the tympanic membrane and sliding
      within the joints. It could be shown that each parameter had influence over the
      entire or sections of the frequency range in different magnitudes. A chart was
      derived to show the influence of each parameter depending on the frequency. The
      results allow improved distinguishing between parameters being relevant for a FEM
      simulation of the middle ear and those that can be neglected. This could
      contribute to further improvement of FEms of the middle ear.

PMID- 20128743
TI  - A simple new device to examine human stance: the totter-slab.
AB  - This article describes a new measuring device to investigate balancing strategies
      of human stance: the totter-slab, i.e., a standing plate suspended with steel
      cables to hooks on a steel frame. First, we analysed the physical properties of
      the device by recording free oscillations under different conditions [varying
      amplitude, mass and centre of mass (COM) height]. This allowed us to determine
      the eigenfrequency f and the damping coefficient D<1 Ns/m for each trial. The
      trials showed that the measured damped eigenfrequency of f is approximately 0.63
      Hz is barely dependent on the mass loaded. The ratio D/M is approximately 0.015
      1/s is a constant almost independent of the different conditions. Furthermore, we
      determined the stiffnesses of the suspending cables and their suspension points
      to check for potential energy storage capacity of the totter-slab. We found that
      the totter-slab is a useful, well-defined, reliable and developable measuring
      device for different non-rigid-ground stance conditions. In a second part of the
      investigation, we compared the frequency spectra of six subjects balancing on the
      totter-slab with their spectra while standing quietly on a force plate fixed to
      the ground. The totter-slab spectra showed two distinct, dominant peak regions at
      approximately 0.3 and 1.1 Hz. This finding enforces the double inverted pendulum
      to be an adequate model particularly for balancing on the totter-slab. Compared
      with the firm ground condition, these two peak regions were more pronounced when
      balancing on the totter-slab. However, there is a variety of frequencies in the
      region 0.2...1.5 Hz specific for an individual subject in both balancing
      conditions.

PMID- 20128744
TI  - Minimally invasive rapid palatal expansion with an implant-supported hyrax screw.
AB  - Rapid palatal expansion is indicated in the orthopedic treatment of transverse
      maxillary deficiency for correction of severe crossbite. The fixation of the
      appliance at the tooth crowns leads to more tipping connected with resorptions at
      the buccal cortical bone, fenestrations and gingival retraction. The aim of the
      present study was focused on the improvement of bodily movement and optimization
      of the surgical osteotomy (Glassman's technique) in adult patients with
      application of the Dresden Distractor (DD). In 18 patients, the new method with a
      special mechanism of adaptation involving minimized surgical intervention and
      direct fixation of the hyrax screw by one implant and one bone screw was tested.
      The implants were loaded directly by activation of the hyrax screw two times per
      day. CT scans were taken before and 6 months after insertion of the DD. In the
      horizontal and vertical planes there was a V-shaped opening of the suture in
      anterior and cranial direction, corroborating previous studies. Dental arch also
      showed this V-shape, indicating tooth protection. DD is a suitable minimally
      invasive tooth-independent bone-borne expansion method, protecting teeth and
      causing skeletal as well as dental effect with tipping reduced by 10 degrees.

PMID- 20128745
TI  - [Analytical computational model for the determination of the influence of design
      and surgical factors on the range of motion of total hip replacements].
AB  - Impingement and dislocations rank among the frequent failure causes of hip
      endoprotheses. The further optimization of endoprotheses requires a comprehensive
      mathematical description of the kinematics with consideration of surgical and
      design parameters. For the investigation of dislocation behavior, spatial
      movements up to impingement with associated load scenarios should be generated.
      We present fundamentals for the determination of the range of motion of total hip
      replacements with consideration of multidirectional, superimposed movements.
      Therefore, the remaining angle, e.g., of abduction/adduction or internal/external
      rotation depending on flexion/extension can be calculated. Thereby, the
      substantial design parameters such as head and neck diameter, CCD angle and head
      coverage are considered. Moreover, the position of the acetabular cup in terms of
      inclination and anteversion angle as well as neck anteversion is considered.
      Using this approach, especially designed for superimposed movements, residual
      range of motion for given movements, e.g., abduction or internal rotation for
      given angles of flexion/extension can be calculated. Thus, the critical
      dislocation-initiating joint positions for primary or revision total hip
      arthroplasty can be determined for arbitrary superimposed movements;
      subsequently, the operating surgeon can evaluate the maximum range of motion for
      a given implant position. Additionally, the calculations are of help for further
      geometrical optimization of implants. The calculation algorithms can be used to
      create ROM maps (graphical illustration of the range of motion depending on
      implant position) which support the operating surgeon in placement of the implant
      components. Moreover, our results are utilized for experimental test setups to
      analyze impingement and subluxation.

PMID- 20128746
TI  - Hemocompatible, pulsed laser deposited coatings on polymers.
AB  - State-of-the-art non-thrombogenic blood contacting surfaces are based on heparin
      and struggle with the problem of bleeding. However, appropriate blood flow
      characteristics are essential for clinical application. Thus, there is increasing
      demand to develop new coating materials for improved human body acceptance.
      Materials deposited by vacuum coating techniques would be an excellent
      alternative if the coating temperatures can be kept low because of the applied
      substrate materials of low temperature resistance (polymers). Most of the
      recently used plasma-based deposition techniques cannot fulfill this demand.
      However, adequate film structure and high adhesion can be reached by the pulsed
      laser deposition at room temperature, which was developed to an industrial-scaled
      process at Laser Center Leoben. Here, this process is described in detail and the
      resulting structural film properties are shown for titanium, titanium nitride,
      titanium carbonitride, and diamond-like carbon on polyurethane, titanium and
      silicon substrates. Additionally, we present the biological response of blood
      cells and the kinetic mechanism of eukaryote cell attachment. In conclusion, high
      biological acceptance and distinct differences for the critical delamination
      shear stress were found for the coatings, indicating higher adhesion at higher
      carbon contents.

PMID- 20128747
TI  - Preparation of porous PLGA microspheres with thermoreversible gel to modulate
      drug release profile of water-soluble drug: bleomycin sulphate.
AB  - Bleomycin sulphate-loaded porous microspheres were prepared using modified
      solvent evaporation method (w/o/w) using PLGA50:50 as a polymeric system. The
      prepared microspheres were incorporated in pluronic (F127) based thermoreversible
      gel to develop a depot formulation. Various process parameters as solvent
      evaporation temperature and formulation parameters such as surfactant
      concentration, volume of internal and external phase and drug-to-polymer ratio
      were optimized for enhancing percentage drug entrapment, percentage drug loading
      and desired release profile by controlling size and porosity of the microspheres.
      Microspheres were characterized for particle size, zeta potential, surface
      morphology, percentage drug loading and in vitro drug release study after
      incorporated in gel. The formulated microspheres were porous in nature and showed
      biphasic in vitro drug release profile. The microspheres incorporated in pluronic
      (F127) gel showed sustained release up to 1 week and may be useful for treatment
      of squamous cell carcinoma with better therapeutic effect.

PMID- 20128748
TI  - Health care leadership, quality and safety.

PMID- 20128749
TI  - Leadership transformation in Queensland Health.

PMID- 20128750
TI  - Developing and implementing an action-oriented staff survey: Queensland Health
      and the "Better Workplaces" initiative.

PMID- 20128751
TI  - Actions and results from the Queensland Health "Better Workplaces" staff opinion
      survey.

PMID- 20128752
TI  - Practising inspired leadership: the use of applied theatre "prophetical" in the
      executive Leadership Development Program for Queensland Health.

PMID- 20128753
TI  - Patient safety -- a balanced measurement framework.
AB  - Evidence of the unacceptably high incidence of patient harm associated with
      health care has resulted in patient safety becoming a major reform agenda.
      Despite significant investment by governments on strategies to reduce patient
      harm, confusion still exists on how to measure patient safety. While the goal of
      patient safety is harm prevention, most of the measurement focus has been on
      counting incident reports. The (ab)use of reported incident data to measure both
      technical safety performance (injury rates) and evaluate the effectiveness of
      safety improvement initiatives continues to confuse and mislead consumers,
      funders and providers of health care. This paper proposes a simple measurement
      framework for patient safety which balances the elements of: learning, action,
      performance, patient experience, and staff attitudes and behaviour. Application
      of this framework to current priority areas should be used as a basis for patient
      safety improvement at clinical unit, hospital, state and national levels.

PMID- 20128754
TI  - Should patient safety be more patient centred?
AB  - In a patient-centred health system the views, experiences and rights of the
      patient drive the way that care is delivered. There is now an increasing emphasis
      on patient-centredness as an essential characteristic of safe and high quality
      care, but to date the involvement of patients in patient safety activities has
      been limited. The views and priorities of patients are not always valued in
      safety and quality work, and their perspectives are rarely included in activities
      such as incident investigation. We propose six areas of action to make patient
      safety more patient centred and hypothesise that the replacement of industrial
      safety models with a patient-centred model of safety culture will improve
      clinicians' ability to engage with safety initiatives.

PMID- 20128755
TI  - Using research to make health care safer.
AB  - There is a fine balance that needs to be maintained between research and
      improvement in safety and quality in health care - when do we need more research
      and when can we just get on with it? The moral imperative to improve care may
      have been a distractor, preventing adequate attention to research. Three research
      areas are proposed as current priorities for patient safety: getting evidence
      into practice, measurement of safety, and the evaluation of complex
      interventions. A focus on these areas should ensure that research becomes more
      central to the process of making health care safer.

PMID- 20128756
TI  - Statistical process control part 1: a primer for using statistical process
      control in health care process improvement.

PMID- 20128757
TI  - Statistical process control part 2: using statistical process control to measure
      process improvement in patient flow.

PMID- 20128758
TI  - Multifaceted guideline implementation strategies improve early identification and
      management of osteoporosis.
AB  - BACKGROUND: Osteoporosis contributes significantly to fractures, subsequent
      disability and premature mortality in Australia. Better detection and management
      of osteoporosis will reduce unnecessary health expenditure. OBJECTIVE: To
      evaluate, in one large tertiary metropolitan hospital, the orthopaedic health
      care team's approach to osteoporosis guideline implementation to improve early
      identification and management of osteoporosis. METHODS: This paper describes the
      implementation of multifaceted strategies to improve health-promoting behaviours
      and the uptake of osteoporosis guidelines by staff in the orthopaedic outpatient
      clinic at one metropolitan hospital, reflecting organisational and individual
      commitment to embedding guideline recommendations into routine practice.
      Implementation strategies were aimed at the requirements and perspectives of
      different stakeholder groups. Five audit datasets were compared: 62 patient
      records in two baseline audits, and three post-implementation audits of 31
      patient records, collected over the following 3-month periods (August 2006 to
      April 2007). All audits used the same criteria to assess compliance with clinical
      guidelines, and outcomes of implementation strategies. RESULTS: There was
      consistent improvement in compliance with osteoporosis guidelines over the audit
      periods. Comparing baseline and immediate post-implementation data, there was a
      significant improvement (P < 0.05) in the percentage of patients with likely
      fragility fractures who were identified with an osteoporotic fracture. The
      percentage of patients who had a likely fragility fracture, with whom staff
      communicated about their problems and how to deal with them, increased
      consistently over all post-implementation audit periods. For patients with
      established osteoporosis who presented with fragility fractures, there was
      sustained improvement over the audit periods in the percentage provided with
      guideline-based care. CONCLUSION: This study highlights that appropriate and
      targeted intervention strategies can be effective if modelled on best practice
      guideline implementation approaches with the use of a coordinated post-fracture
      management approach to osteoporosis.

PMID- 20128759
TI  - Standardising practices through form design and education improves insulin
      management.
AB  - Diabetes is common in hospitalised patients and insulin is frequently required
      for management. Insulin is a high-risk drug, accounting for about 15% of reported
      medication-related incidents. Despite its complexity, insulin management in
      hospitals is often undertaken by junior and non-specialist staff. Improving
      insulin management requires addressing safe prescribing and administration as
      well as quality use of insulin. Common errors in insulin use are well documented
      and can be addressed through form design and enhancing decision support. We
      undertook to improve insulin management using a locally proven improvement
      methodology. New forms were developed for intravenous and subcutaneous insulin
      and blood glucose management. Audited pilot studies in four hospitals confirmed
      improved insulin management without adversely impacting on overall diabetes
      management as assessed using Glucometrics. Subsequently, the forms have been
      introduced to 70% of Queensland public hospitals with roll-out to remaining
      hospitals continuing. Large-scale standardisation of insulin management is
      feasible.

PMID- 20128760
TI  - Evaluating multidisciplinary health care teams: taking the crisis out of CRM.
AB  - High-reliability organisations are those, such as within the aviation industry,
      which operate in complex, hazardous environments and yet despite this are able to
      balance safety and effectiveness. Crew resource management (CRM) training is used
      to improve the non-technical skills of aviation crews and other high-reliability
      teams. To date, CRM within the health sector has been restricted to use with
      "crisis teams" and "crisis events". The purpose of this discussion paper is to
      examine the application of CRM to acute, ward-based multidisciplinary health care
      teams and more broadly to argue for the repositioning of health-based CRM to
      address effective everyday function, of which "crisis events" form just one part.
      It is argued that CRM methodology could be applied to evaluate ward-based health
      care teams and design non-technical skills training to increase their efficacy,
      promote better patient outcomes, and facilitate a range of positive personal and
      organisational level outcomes.

PMID- 20128761
TI  - Digital pen and paper technology is an effective way of capturing variance data
      when using arthroplasty clinical pathways.
AB  - The aim of this study was to test the effectiveness of digital pen and paper
      technology (DP&PT) to capture clinical pathway variance data in real time and at
      the point of care for patients on an arthroplasty pathway. This study was
      conducted across multiple departments providing orthopaedic services in a public
      health care facility. Treating clinicians were required to record variance data
      on a predefined coded template, and these data were uploaded to a database for
      analysis and reporting. The information could be represented in a web-based user
      interface for immediate review. User acceptance, length of stay (LOS), accuracy
      of data, and reliability of the DP&PT hardware were measured. User acceptance was
      high; LOS reduced; and the data and hardware were, respectively, found to be
      accurate and robust. This technology provides a dependable, real-time solution to
      transform handwritten clinical data into a digital format. The data available
      will help inform clinicians of areas for clinical practice improvement, and
      provide ongoing monitoring of care processes for patients on a clinical pathway.
      Future studies should aim to assess if using this method to capture variance data
      is a more efficient and effective means of informing clinical decision making
      than retrospective review processes.

PMID- 20128762
TI  - Dementia risk reduction in primary care: what Australian initiatives can teach
      us.
AB  - Only limited research has been undertaken to identify factors that impede or
      facilitate the implementation of evidence-based health promotion, prevention and
      early intervention (PPEI) activities within primary practice. We examined recent
      Australian initiatives that encouraged primary care practitioners to implement
      PPEI activities to reduce the risk of chronic disease, particularly those that
      have focused on lifestyle risk factors. The aim was to identify barriers and
      facilitators to the uptake of these activities to inform the Australian National
      Dementia Prevention Strategy. Barriers that were consistently reported across
      evaluations and that appear to be of most concern to Australian general
      practitioners include the issues of financial remuneration and time constraints
      secondary to heavy work commitments. Factors that were effective in overcoming
      barriers included the integration of interventions within existing activities,
      the specification of a clear, funded role for practice nurses and the support of
      the Australian General Practice Network. It was concluded that these factors
      should be considered if PPEI activities for dementia are to be successfully
      incorporated within primary care.

PMID- 20128763
TI  - Necessity breeds innovation: GPs help prevent an emergency department closure.
AB  - In January 2006 the Maryborough Base Hospital in Queensland faced imminent
      closure of its emergency department (ED) due to a shortage of senior medical
      staff. At the same time patient confidence in Queensland Health was low. During
      consultation forums, the community had made it clear that their priority was to
      maintain emergency services in Maryborough. In search of a solution, the Fraser
      Coast District Health Service asked Maryborough general practitioners to work in
      the Maryborough Hospital ED and/or in the internal medicine ward as Visiting
      Medical Officers. While this represented a solution to the problem, there was
      much to be considered before such a plan could be put into place.

PMID- 20128764
TI  - Self-sufficiency in intern supply: the impact of expanded medical schools,
      medical places and rural clinical schools in Queensland.
AB  - OBJECTIVE: The doctor shortage in Australia generally, and the rural shortage in
      particular, has led to an increase in medical schools, medical places and rural
      training. If effective, these strategies will first impact on the intern
      workforce. We studied the source of interns in Queensland. METHODS: Analysis of
      number, source and location of interns by Rural, Remote and Metropolitan Area
      (RRMA) classification (an index of remoteness) from university and health
      department records (2003-2008). Odds ratios compared the likelihood of intern
      supply from Queensland universities and rural clinical schools. RESULTS: Most
      interns in Queensland graduated from Queensland universities in 2007 (287 [72%])
      and 2008 (344 [84%]). Proportions increased across all three RRMA groups from:
      82% to 93% in RRMA1; 56% to 68% in RRMA2 and 67% to 79% in RRMA3. The University
      of Queensland (UQ) provides most interns in all RRMA locations including RRMA3,
      and this increased from 2007 (n = 33 [35%]) to 2008 (n = 57 [58%]). Interns from
      interstate decreased from 61 (15%) in 2007 to 40 (10%) in 2008. Interns from
      overseas fell from 53 (13%) in 2007 to 27 (7%) in 2008. Rural clinical schools
      compared with traditional urban-based schools were more likely to supply interns
      to RRMA3 than RRMA1 hospitals in 2007 (OR, 8.8; 95% CI, 4.6-16.7; P < 0.0001) and
      2008 (OR, 6.5; 95% CI, 3.5-12.2; P < 0.0001). CONCLUSIONS: Queensland is close to
      self-sufficiency in intern supply and will achieve this in the next few years.
      Rural clinical schools are playing an important role in producing interns for
      RRMA3 hospitals. Due to its large cohort, UQ remains the major provider across
      all RRMA groups.

PMID- 20128765
TI  - People with an intellectual disability in the discourse of chronic and complex
      conditions: an invisible group?

PMID- 20128766
TI  - Are immigrants at risk of heart disease in Australia? A systematic review.
AB  - We systematically reviewed the peer-reviewed literature to establish the
      prevalence of cardiovascular disease (CVD) among immigrants in Australia and
      whether being an immigrant is a CVD risk factor. Of 23 studies identified, 12
      were included. Higher prevalence of CVD was found among Middle Eastern, South
      Asian and some European immigrants. Higher prevalence of CVD risk factors was
      found among Middle Eastern and Southern European immigrants. Higher alcohol
      consumption was found among immigrants from New Zealand, the United Kingdom and
      Ireland. Smoking and physical inactivity were highly prevalent among most
      immigrants.

PMID- 20128767
TI  - Third year of the Models of Care Section.

PMID- 20128768
TI  - Medical model for hospital in the home: effects on patient management.
AB  - OBJECTIVE: To evaluate the effects of a change to a medical model for hospital in
      the home (HITH). DESIGN AND SETTING: This was a retrospective pre- and post
      intervention study in the Royal Melbourne Hospital HITH between 28 March 2002 and
      29 March 2006. The intervention was daily review, by medical staff, of all
      patients in their homes. 159 patients with cellulitis or deep venous thrombosis
      (DVT) admitted to HITH in the pre-intervention period were matched with patients
      admitted in the post-intervention period. MAIN OUTCOME MEASURES: HITH length of
      stay (LOS), scheduled and unscheduled hospital review rates (during the HITH
      admission), and hospital admission rates. RESULTS: Post-intervention, median LOS
      decreased (6 v 5 days [P = 0.03]). There were also significant reductions in
      scheduled and unscheduled review rates (40.9 v 1.3 reviews/100 patients [P <
      0.001] and 15.7 v 4.4 reviews/100 patients [P = 0.001], respectively) and
      hospital admission rates (10.7 v 3.8 admissions/100 patients [P = 0.02]).
      Although there was no difference in adverse event rates between the two periods
      (3.1 v 2.5/100 patients [P = 0.50]), there was a significantly greater
      complication rate post-intervention (57.2 v 92.4/100 patients [P < 0.001]).
      CONCLUSION: The medical model resulted in significant improvements in process
      measures and clinical endpoints among patients with cellulitis and DVT.

PMID- 20128769
TI  - Admission variables predicting short lengths of stay of acutely unwell older
      patients: relevance to emergency and medical short-stay units.
AB  - OBJECTIVE: To help develop criteria to identify older patients suitable for
      admission to medical short-stay units, by determining predictors of length of
      stay (LOS) of 3 days or less. METHODS: The data were prospectively collected from
      consecutive older patients admitted from the emergency department of a university
      hospital to an acute geriatric medicine service. Data included active medical
      diagnoses, the Modified Barthel Index (MBI), the Timed Up and Go (TUG) test, and
      demographic information. Logistic regression was used to model the probability of
      LOS of 3 days or less (short LOS). RESULTS: Among 2036 patients discharged alive
      from hospital (mean age, 82 years; median LOS, 7 days), 398 had a short LOS
      (median, 2 days), while 1638 had a long LOS (median, 9 days). In logistic
      regression analysis, the main independent predictors of short LOS were an MBI
      score > 15/20 (OR, 2.98; 95% CI, 1.97-4.49), ability to perform the TUG test (OR,
      2.08; 95% CI, 1.34-3.24) and absence of delirium (OR, 2.66; 95% CI, 1.56-4.54).
      Patients without infection, anaemia, gastrointestinal disorder and stroke were
      also more likely to have a short LOS in multivariate analysis (all P < 0.05).
      CONCLUSION: Preserved function, measured using the MBI and TUG, and the absence
      of delirium are strong predictors of short LOS. In conjunction with early,
      skilled clinical evaluation, these criteria could be used to select older
      patients presenting to the emergency departments for admission to short-stay
      units.

PMID- 20128770
TI  - Discharge delay in acute care: reasons and determinants of delay in general ward
      patients.
AB  - To identify the reasons and determinants of discharge delay in acute care
      patients, information associated with delayed discharge was extracted from the
      medical record of 1958 patients in a tertiary referral hospital in New South
      Wales. A logistic regression model was used to examine the association between
      demographic factors and reasons for discharge delay. Delayed discharge was most
      commonly associated with the patient's medical conditions, delayed health care or
      medical consultation, delayed diagnostic services and delayed allied health
      services. Elderly patients, those living alone and patients from a non-English
      speaking background were more likely to have these reasons for delayed discharge.

PMID- 20128771
TI  - Z-FA.FMK activates duodenal epithelial cell proliferation through oxidative
      stress, NF-kappaB and IL-1beta in D-GalN/TNF-alpha-administered mice.
AB  - This study was designed to evaluate the effect of Z-FA.FMK (benzyloxycarbonyl-l
      phenylalanyl-alanine-fluoromethylketone), a pharmacological inhibitor of
      cathepsin B, on the proliferation of duodenal mucosal epithelial cells and the
      cellular system that controls this mechanism in these cells in vivo. For this
      investigation, BALB/c male mice were divided into four groups. The first group
      received physiological saline, the second group was administered Z-FA.FMK, the
      third group received D-GalN (D-galactosamine) and TNF-alpha (tumour necrosis
      factor-alpha) and the fourth group was given both D-GalN/TNF-alpha and Z-FA.FMK.
      When D-GalN/TNF-alpha was administered alone, we observed an increase in IL-1beta
      positive and active NF-kappaB-positive duodenal epithelial cells, a decrease in
      PCNA (proliferative cell nuclear antigen)-positive duodenal epithelial cells and
      an increase in degenerative changes in duodenum. On the other hand, Z-FA.FMK
      pretreatment inhibited all of these changes. Furthermore, lipid peroxidation,
      protein carbonyl and collagen levels were increased, glutathione level and
      superoxide dismutase activity were decreased, while there was no change in
      catalase activity by D-GalN/TNF-alpha injection. On the contrary, the Z-FA.FMK
      pretreatment before D-GalN/TNF-alpha blocked these effects. Based on these
      findings, we suggest that Z-FA.FMK might act as a proliferative mediator which is
      controlled by IL-1beta through NF-kappaB and oxidative stress in duodenal
      epithelial cells of D-GalN/TNF-alpha-administered mice.

PMID- 20128772
TI  - Oestrogen regulates proliferation and differentiation of human islet-derived
      precursor cells through oestrogen receptor alpha.
AB  - E2 (oestradiol-17beta) is an important hormone that regulates various cell
      functions including insulin production. hIPCs (human islet-derived precursor
      cells) are capable of proliferating and differentiating into cells that secrete
      insulin in response to glucose in vivo and in vitro. However, the effect of E2 on
      hIPCs is currently unclear. In this study, we found that ERalpha (oestrogen
      receptor alpha), but not ERbeta, was expressed on hIPCs, and E2 promoted the
      proliferation and inhibited the differentiation of adult hIPCs. Although fetal
      hIPCs also express ERalpha, no effect of E2 on the fetal hIPCs was observed,
      suggesting differing roles of E2 at different stages of pancreatic development.
      This study indicates that E2 may be one of the key factors that control the
      turnover of adult pancreatic beta cells by regulating the proliferation and
      differentiation of adult hIPCs through ERalpha.

PMID- 20128773
TI  - Organ sales needn't be exploitative (but it matters if they are).
AB  - This paper considers two arguments that are common in the literature on organ
      sales. First, organ sales are exploitative and therefore should not be permitted.
      Second, it doesn't matter whether organ sales are exploitative or not; the only
      thing that matters is that we do what is in the interests of those who need to be
      protected. In this paper, I argue that both of these arguments are too
      simplistic. My intention, however, is not to argue for or against organ sales. My
      conclusion, rather, is simply that we cannot hope to address the issue of organ
      sales if we lack a good understanding of exploitation. We should not attempt to
      answer the question of whether or not organ sales should be banned on the grounds
      that they are exploitative without acknowledging and addressing the nuances
      involved in understanding exploitation.

PMID- 20128774
TI  - Bayesian modeling of ChIP-chip data through a high-order Ising model.
AB  - ChIP-chip experiments are procedures that combine chromatin immunoprecipitation
      (ChIP) and DNA microarray (chip) technology to study a variety of biological
      problems, including protein-DNA interaction, histone modification, and DNA
      methylation. The most important feature of ChIP-chip data is that the intensity
      measurements of probes are spatially correlated because the DNA fragments are
      hybridized to neighboring probes in the experiments. We propose a simple, but
      powerful Bayesian hierarchical approach to ChIP-chip data through an Ising model
      with high-order interactions. The proposed method naturally takes into account
      the intrinsic spatial structure of the data and can be used to analyze data from
      multiple platforms with different genomic resolutions. The model parameters are
      estimated using the Gibbs sampler. The proposed method is illustrated using two
      publicly available data sets from Affymetrix and Agilent platforms, and compared
      with three alternative Bayesian methods, namely, Bayesian hierarchical model,
      hierarchical gamma mixture model, and Tilemap hidden Markov model. The numerical
      results indicate that the proposed method performs as well as the other three
      methods for the data from Affymetrix tiling arrays, but significantly outperforms
      the other three methods for the data from Agilent promoter arrays. In addition,
      we find that the proposed method has better operating characteristics in terms of
      sensitivities and false discovery rates under various scenarios.

PMID- 20128775
TI  - Peyronie's disease compromises the durability and component-malfunction rates in
      patients implanted with an inflatable penile prosthesis.
AB  - OBJECTIVE: To compare the durability and complication rates of surgery to implant
      an inflatable penile prosthesis (IPP) between patients with and without
      Peyronie's disease (PD). PATIENTS AND METHODS: We retrospectively reviewed all
      patients undergoing IPP surgery at one centre (Memphis) between July 1997 and May
      2007. Variables included age at surgery, race, body mass index, presence of PD,
      brand/type of IPP (two vs three pieces), presence of diabetes mellitus (DM),
      active tobacco use, and complications. The result were assessed using t-tests,
      chi-square and regression analysis, with P < 0.05 considered to indicate
      significant differences. RESULTS: In all, 79 men were analysed (mean age 59.8
      years, range 38.1-81.5). Nine (11%) patients had PD and had a IPP implanted, with
      penile modelling. Overall, 43 (54%) patients had pre-existing DM and 51 (65%)
      actively used tobacco. At a mean (range) follow-up of 19.6 (0.1-115.3) months,
      six (8%) patients had component malfunctions. Of these, three had DM and four
      actively smoked. Of the nine patients with PD, three developed component
      malfunctions, vs three (4%) who did not have PD (P= 0.002). Both groups had
      similar infection rates (P= 0.98). The mean (range) time to component malfunction
      was 4.3 (0.1-9.6) months, which was longer (but not significantly) in the PD
      group, with a mean (median, range) of 10.9 (6.3, 1.1-9.6) months, than the 3.0
      (1.0, 0.2-7.9) months in the group without PD (P= 0.4). Groups were matched for
      rates of DM (P= 0.1) and tobacco use (P= 0.2). PD was a significant predictor of
      component malfunction on both univariate (P= 0.001) and multivariate analysis (P=
      0.002) when adjusting for age (P= 0.2), body mass index (P= 0.7), DM (P= 0.3) and
      tobacco use (P= 0.8). CONCLUSION: Patients with PD implanted with a IPP, with
      penile modelling, had significantly higher component malfunction rates. Further,
      PD independently predicted component malfunction. These findings might be related
      to stress on the device at the time of surgery, during use, or both. Further
      study into this relationship is required.

PMID- 20128776
TI  - Face, content and construct validation of the first virtual reality laparoscopic
      nephrectomy simulator.
AB  - OBJECTIVE: To evaluate the face, content and construct validity, and to identify
      whether participants improved with practice, for the Procedicus MIST Nephrectomy
      simulator (Mentice, Gothenburg, Sweden), which incorporates force feedback and
      can record numerous performance measures (metrics) during the simulation, and
      which is the first virtual reality simulator for laparoscopic nephrectomy.
      SUBJECTS AND METHODS: Eight expert urological laparoscopic surgeons, 10 novices
      and 10 trainee urologists completed at least one simulated retroperitoneal
      radical nephrectomy. They completed a structured questionnaire to assess face and
      content validity; the performance of experts and novices were then compared to
      evaluate construct validity. RESULTS: Face validity was established by the
      experts who all felt the simulator was a good training tool. Content validity was
      established by the experts who rated all aspects of the simulator as above
      average for realism. When performance metrics were analysed, experts completed
      the simulated nephrectomy significantly faster than novices, with fewer errors,
      less simulated haemorrhage and less tool travel, which established construct
      validity. After practice, both novices and trainees were able to perform the
      simulation faster, with fewer errors, less blood loss and less tool travel.
      CONCLUSIONS: This study has established the face, content and construct validity
      for the Procedicus MIST Nephrectomy. The simulator can distinguish experts from
      novices and it has potential as a laparoscopic training tool for urology.

PMID- 20128777
TI  - Intractable haematuria: long-term results after selective embolization of the
      internal iliac arteries.
AB  - OBJECTIVE: To determine the feasibility and efficacy of transarterial
      embolization (TAE) in haemorrhagic urological emergencies, and to assess the
      perioperative morbidity, effect of timing of intervention on the requirement for
      blood transfusion, and the long-term follow-up. PATIENTS AND METHODS: Between
      October 1997 and March 2009, 44 patients (30 men and 14 women; mean age 79 years,
      range 51-95) with intractable haematuria secondary to advanced pelvic tumour
      arising from or invading the bladder, underwent internal iliac TAE. Twenty-four
      patients had transitional carcinoma of the urinary bladder, 12 adenocarcinoma of
      the prostate, five carcinoma of the uterus, one cancer of the vagina, two
      carcinoma of the rectum, three carcinoma of the kidney, two simultaneous
      carcinoma of prostate and bladder, one simultaneous carcinoma of prostate and
      kidney and one had haemorrhagic cystitis after radiotherapy. RESULTS: TAE of the
      internal iliac arteries produced initial complete control of bleeding in 36 of
      the 44 patients (82%). At a mean (range) follow-up of 10.5 (1-97) months TAE
      there was permanent control of bleeding in 19 (43%) patients. A second TAE
      session was use in five (11%) patients and it was successful in two of them.
      There were 24 patients (55%) who required a mean of 4 (1-17) transfusion units
      before embolization; only 13 (30%) required more blood products after TAE. The
      mean haematocrit level before and after TAE was 27% and 31% (P < 0001), and the
      respective haemoglobin level were 8.7 and 10.3 g/dL (P < 0001). During the follow
      up there were no major complications related to TAE; minor complications were
      post-TAE syndrome in 12 (27%) patients, fever (11%), gluteus pain (14%), nausea
      (2%), and exterior genital oedema (5%). The 6- and 12-month mortality rates were
      66% (29 patients) and 18% (eight), respectively. CONCLUSIONS: TAE should be
      considered as an alternative less-invasive palliative measure and the treatment
      of choice in these situations. TAE should always be bilateral, the catheter
      should advance distally to the origin of the superior gluteal artery and the
      artery embolized with unresorbable particles. Our study confirms the efficacy and
      safety of TAE in patients with pelvic malignancy, and indicates that this
      technique should be considered before surgery. The procedure combines the
      benefits of a minimally invasive approach in decreasing the cost of surgery and
      operating time, while maintaining low blood loss and analgesia requirement.

PMID- 20128778
TI  - Urodynamic interpretation of changing bladder function and voiding pattern after
      radical prostatectomy: a long-term follow-up.
AB  - OBJECTIVE: To investigate and compare changes in the bladder function after
      radical prostatectomy (RP) and to correlate changes in subjective voiding
      symptoms with the observed changes in function. PATIENTS AND METHODS: In 72
      patients who had RP between 2003 and 2004, we serially evaluated urodynamic
      studies (UDS) before RP and at 3, 6 and 36 months afterward. The short-form
      International Continence Society-male symptom questionnaire was also repeated at
      corresponding periods. Changes in bladder contraction and storage function after
      RP were compared for changes in subjective symptoms. RESULTS: On serial UDS,
      there were reductions in maximum cystometric capacity, maximum detrusor pressure
      and maximum urethral closure pressure (MUCP) at 3 months, after which all
      remained relatively unchanged. On the questionnaire, the voiding symptom domain
      score improved (8.04 to 4.82, P < 0.001) while the storage domain score
      significantly and progressively worsened, beginning from 3 months (2.25 to 3.78,
      P= 0.04), resulting in an unchanged overall urinary symptom-related quality of
      life at 3 years. The incidence of detrusor overactivity increased from 37.5%
      before RP, to 45.8% at 3 months and 51.4% at 3 years. At 3 years, a recurring
      postvoid residual urine volume was the cause of the deterioration in the voiding
      symptom domain score, while a prominent reduction in MUCP resulted in a
      deterioration in the storage symptom score. CONCLUSIONS: There is a reduction in
      bladder capacity, detrusor and sphincteric activity immediately after RP,
      stabilizing thereafter but remaining significantly reduced at 3 years. Although
      voiding symptoms improved in most men, the significant deterioration in storage
      symptoms, which might be attributed to sphincteric incompetence in addition to
      increased detrusor overactivity, became a source of overall urinary bother in the
      long term.

PMID- 20128779
TI  - Laparoscopic ureterolysis with omental wrap for idiopathic retroperitoneal
      fibrosis.
AB  - OBJECTIVE: To describe various approaches for ureterolysis with an omental wrap
      using minimally invasive techniques, as surgery for idiopathic retroperitoneal
      fibrosis includes tissue biopsy, ureterolysis, and intraperitonealization or
      omental wrap. PATIENTS AND METHODS: Since 2006 we have performed ureterolysis in
      four patients diagnosed with retroperitoneal fibrosis in two institutions. The
      ureterolysis in two cases was bilateral, using a standard laparoscopic approach
      for one case and a hand-assisted technique for the other. Unilateral ureterolysis
      was completed using a standard laparoscopic approach in one case and was
      converted to a hand-assisted technique in the other due to difficulty with
      ureteric identification. An omental wrap was used after ureterolysis for all
      renal units. RESULTS: A minimally invasive technique was used for all
      ureterolysis procedures and none required open conversion. There was fascial
      dehiscence after surgery at the hand-port site in one patient, and required re
      operation for wound closure. The median (range) hospital stay for all patients
      was 2.5 (2-10) days and the median blood loss was 100 (50-550) mL. No patient
      required a blood transfusion. At a median 16.5 (12-32) months of follow-up, there
      was symptomatic and radiographic success in all patients. CONCLUSIONS:
      Ureterolysis can be a challenging operation depending on the extent of the
      retroperitoneal mass. An understanding of various laparoscopic techniques can
      provide the flexibility for successful completion of nearly all of these
      procedures using a minimally invasive approach.

PMID- 20128780
TI  - The depth of the prostatic apex is an independent predictor of positive apical
      margins at radical prostatectomy.
AB  - OBJECTIVE: To determine the effect of a deep and narrow pelvis on apical positive
      surgical margins (PSM) at radical prostatectomy (RP), controlling for other
      clinical and pathological variables and surgical approach, i.e. open retropubic
      (RRP) vs laparoscopic (LRP), as apical dissection is expected to be more
      challenging at RP with a prostate situated deep in a narrow pelvis. PATIENTS AND
      METHODS: From July 2003 to January 2005, 512 consecutive patients with
      preoperative prostate magnetic resonance imaging (MRI) underwent RRP or LRP with
      no previous radio- or hormonal therapy. An additional 74 patients with
      preoperative MRI undergoing RP from December 2001 to June 2007 who had an apical
      PSM were also included, with 586 patients comprising the study population. Bony
      and soft-tissue pelvic dimensions, including interspinous distance (ISD), bony
      (BFW) and soft tissue (SW) pelvic width, apical prostate depth (AD) and symphysis
      pubis angle, were measured on preoperative MRI. The pelvic dimension index (PDI),
      bony width index (BWI) and soft-tissue width index (SWI) were defined as ISD/AD,
      BFW/AD and SW/AD, respectively. Multivariate logistic regression was used to
      assess the effect of pelvic dimensions on apical PSM, controlling for surgical
      approach and clinical and pathological variables. RESULTS: There was no
      significant difference in ISD, BFW, SW or symphysis angle between patients with
      and without apical PSM. The AD was significantly greater in men with an apical
      PSM and consequently PDI, BWI and SWI were significantly lower in men with an
      apical PSM. Each of PDI, AD, BWI and SWI was a significant independent predictor
      of apical PSM, independent of surgical approach, and other clinicopathological
      variables. The main limitations of the study were that it was retrospective, and
      the relatively few patients with apical PSM. CONCLUSIONS: Apical prostate depth
      is an independent risk factor for apical PSM at RP. MRI pelvimetry might allow
      for preoperative planning of the approach to RP.

PMID- 20128781
TI  - Prognostic significance of a positive surgical margin in pathologically organ
      confined prostate cancer.
AB  - OBJECTIVE: To identify risk factors of a positive surgical margin (PSM) and the
      significance of a PSM after radical prostatectomy (RP) on biochemical recurrence
      (BCR) in exclusively pathologically confirmed organ-confined (OC) prostate
      cancer, as despite an excellent prognosis after RP, some patients with
      pathologically confirmed OC disease have BCR, and the prognostic significance of
      a PSM in these men remains unclear. PATIENTS AND METHODS: We assessed 932 men
      with pathologically OC disease who were treated with RP by nine different
      surgeons between 1992 and 2004. The prognostic significance of clinical and
      pathological variables, including tumour volume (TV) and percentage of high-grade
      TV (%HGTV) were assessed. Logistic and Cox regression models were fitted to
      identify risk factors of a PSM and BCR. BCR was defined as a prostate-specific
      antigen (PSA) level of 0.1 ng/mL and increasing after an undetectable PSA level.
      RESULTS: The total PSM rate was 12.9% (120 men); the mean TV (P < 0.001), but not
      %HGTV (P= 0.2) was significantly higher in patients with PSM. TV, nerve-sparing
      RP technique and surgical volume were independent risk factors for a PSM (P=
      0.03). After a median follow-up of 35 months the overall BCR rate was 8.8% (82
      men). Patients with a PSM had significantly higher BCR rates (21.7% vs 6.9%; P <
      0.001). In univariable analysis, a high %HGTV (70.4%) was the most informative
      risk factor of BCR, followed by RP Gleason score (65.8%) and PSM (65.7%). Removal
      of PSM from a multivariable Cox model decreased the accuracy by 12.1% (P <
      0.001). CONCLUSIONS: Our findings show that in OC prostate cancer, the risk of a
      PSM depends on TV, surgical technique and surgical volume. PSM is a significant
      risk factor for BCR. However, only 20% men with OC disease and a PSM develop BCR;
      conversely, 80% of men are cured despite a PSM. Therefore, adjuvant therapy must
      be considered, with caution to avoid unnecessary overtreatment.

PMID- 20128782
TI  - The sphingosine-1-phosphate pathway is upregulated in response to partial
      urethral obstruction in male rats and activates RhoA/Rho-kinase signalling.
AB  - OBJECTIVES: To examine the effect of partial urethral obstruction (PUO) on the
      sphingosine-1-phosphate (S1P, a bioactive lipid shown to modulate smooth muscle,
      SM) pathway in the bladders of male rats, and to determine the effect of PUO on
      the RhoA/Rho-kinase (ROK) pathway, and whether there is a molecular cross-talk
      with the S1P pathways associated with bladder overactivity (S1P1-S1P3, where S1P1
      is associated with nitric oxide-mediated SM relaxation, and S1P2 and S1P3
      receptors are associated more with SM contraction via the ROK pathway). MATERIALS
      AND METHODS: In all, 20 male rats were divided into two groups and underwent PUO
      or a sham operation (control). After 2 weeks all rats were killed humanely and
      bladder specimens used for in vitro organ-bath physiological contractility
      studies, and for mRNA and protein analyses of major S1P/ROK pathway constituents
      via real-time polymerase chain reaction and Western blotting, respectively. In
      addition, early-passage SM cells were transfected with recombinant sphingosine
      kinase (SPHK, the enzyme that converts sphingosine to S1P). RESULTS: Bladders
      from PUO rats had greater mRNA expression of the S1P2 and S1P3 receptors, as well
      as SPHK1, than the sham controls (4.78, 2.04 and 2.72 times, respectively). PUO
      rats also had significantly greater expression of RhoA and ROKalpha (1.76 and
      2.19 times, respectively). Western blotting and organ-bath contractility studies
      showed similar changes at the protein and in vitro functional level, with an
      increased contractility of bladder strips from PUO rats to exogenous S1P.
      Transfection of SPHK into isolated SM cells increased ROK expression.
      CONCLUSIONS: We show for the first time that the S1P signalling pathway is
      significantly upregulated in response to PUO in male rats at both the molecular
      and in vitro functional levels, correlating with an activation of the RhoA/ROK
      pathway. Further, we provide novel data that SPHK overexpression increases ROK
      expression in vitro, suggesting a novel hypothesis of S1P-induced bladder
      overactivity in the mechanism for PUO-induced bladder dysfunction and the S1P
      signalling pathway as a possible therapeutic target for bladder overactivity.

PMID- 20128783
TI  - Prognostic significance of survivin-expressing circulating tumour cells in T1G3
      bladder cancer.
AB  - OBJECTIVE: To evaluate the prognostic significance of survivin in tumour tissues
      and that of survivin-expressing circulating tumour cells (CTCs) in T1G3 bladder
      tumours, as the prognosis of T1G3 bladder cancer is highly variable and
      unpredictable from clinical and pathological prognostic factors. PATIENTS AND
      METHODS: The study included 54 patients with T1G3 non-muscle-invasive bladder
      cancer. Additional inclusion criteria were: tumour size <3 cm, absence of
      carcinoma in situ and multifocality. The planned follow-up was 24 months.
      Survivin was evaluated by reverse transcription-polymerase chain reaction in
      tumour tissues. CTCs were isolated from blood by CELLection Dynabeads
      (Invitrogen, Carlsbad, CA, USA) coated with the monoclonal antibody towards the
      human epithelial cell adhesion molecule. Cells were lysed and Dynabeads Oligo(dT)
      was used to capture poly A + mRNA. cDNA was synthesized and analysed for the
      expression of CD45, CK8 and survivin. The primary endpoint was disease-free
      survival (DFS); the favourable group at 24 months was defined as that with no
      clinical evidence of disease; the unfavourable group was that with evidence of
      recurrent disease or progressive disease. Tumour survivin expression and presence
      of CTC were correlated with DFS. Multivariate analysis was used to investigate
      whether the presence of CTC was an independent indicator of DFS. RESULTS:
      Survivin was found in half of the tumours; patients with survivin-negative
      tumours had a longer DFS than those with survivin-positive tumours (chi-square, P
      = 0.029). CTCs were found in 24/54 patients (44%); 92% of CTC expressed survivin.
      The difference in DFS between CTC-ve and CTC+ve patients was statistically
      significant (chi-square, P < 0.001). The presence of CTC was an independent
      prognostic factor for DFS (P < 0.001). CONCLUSION: The presence of CTC is an
      independent prognostic factor in patients with T1G3 bladder cancer.

PMID- 20128784
TI  - 'Ghost' experiments and the dissection of social learning in humans and animals.
AB  - The focus of this review is the experimental techniques used to identify forms of
      social learning shown by humans and nonhuman animals. Specifically, the 'ghost
      display' and 'end-state' conditions, which have been used to tease apart
      imitative and emulative learning are evaluated. In a ghost display, the movements
      of an apparatus are demonstrated, often through the discrete use of fishing-line
      or hidden mechanisms, without a live model acting directly upon the apparatus so
      that the apparatus appears to be operated as if by a 'ghostly' agent. In an end
      state condition, an observing individual is shown the initial state of the test
      apparatus, the apparatus is then manipulated out-of-sight and then represented to
      the individual in its final state. The aim of the ghost display condition is to
      determine whether individuals are able to emulate by replicating the movements of
      an apparatus, or perform a task, without requiring information about the bodily
      movements required to do so (imitation). The end-state condition is used to
      identify goal-emulation by assessing whether the observer can replicate the steps
      required to solve the task without having been shown the required body actions or
      task movements. The responses of individuals tested with either the ghost display
      and/or end-state conditions are compared to those of further individuals who have
      observed a full demonstration by either a human experimenter or a conspecific.
      The responses of a control group, to whom no information has been provided about
      the test apparatus or required actions, are also compared and evaluated. The
      efficacy of these experimental techniques employed with humans, nonhuman
      primates, dogs, rats and birds are discussed and evaluated. The experiments
      reviewed herein emphasise the need to provide ghost displays and end-state
      conditions in combination, along with full live demonstrations and a no
      information control. Future research directions are proposed.

PMID- 20128785
TI  - A conceptual framework for the colonisation of urban areas: the blackbird Turdus
      merula as a case study.
AB  - Despite increasing interest in urban ecology the factors limiting the
      colonisation of towns and cities by species from rural areas are poorly
      understood. This is largely due to the lack of a detailed conceptual framework
      for this urbanisation process, and of sufficient case studies. Here, we develop
      such a framework. This draws upon a wide range of ecological and evolutionary
      theory and the increasing number of studies of how the markedly divergent
      conditions in urban and rural areas influence the traits of urban populations and
      the structure of urban assemblages. We illustrate the importance of this
      framework by compiling a detailed case study of spatial and temporal variation in
      the urbanisation of the blackbird Turdus merula. Our framework identifies three
      separate stages in the urbanisation process: (i) arrival, (ii) adjustment, and
      (iii) spread. The rate of progress through each stage is influenced by
      environmental factors, especially human attitudes and socio-economic factors that
      determine the history of urban development and the quality of urban habitats, and
      by species' ecological and life-history traits. Some traits can positively
      influence progression through one stage, but delay progression through another.
      Rigorous assessment of the factors influencing urbanisation should thus ideally
      pay attention to the different stages. Urbanisation has some similarities to
      invasion of exotic species, but the two clearly differ. Invasion concerns
      geographic range expansion that is external to the species' original geographic
      range, whilst urbanisation typically relates to filling gaps within a species'
      original range. This process is exemplified by the blackbird which is now one of
      the commonest urban bird species throughout its Western Palearctic range. This is
      in stark contrast to the situation 150 years ago when the species was principally
      confined to forest. Blackbird urbanisation was first recorded in Germany in 1820,
      yet some European cities still lack urban blackbirds. This is especially so in
      the east, where urbanisation has spread more slowly than in the west. The timing
      of blackbird urbanisation exhibits a marked spatial pattern, with latitude and
      longitude explaining 76% of the variation. This strong spatial pattern contrasts
      with the weaker spatial pattern in timing of urbanisation exhibited by the
      woodpigeon Columba palumbus (with location explaining 39% of the variation), and
      with the very weak spatial pattern in timing of black-billed magpie Pica pica
      urbanisation (in which location explains 12% of the variation). Strong spatial
      patterns in timing of urbanisation are more compatible with the leap-frog
      urbanisation model, in which urban adapted or imprinted birds colonise other
      towns and cities, than with the independent urbanisation model, in which urban
      colonisation events occur independently of each other. Spatial patterns in
      isolation do not, however, confirm one particular model. Factors relating to the
      arrival and adjustment stages appear particularly likely to have influenced the
      timing of blackbird urbanisation. Spatial variation in the occurrence of urban
      populations and the timing of their establishment creates opportunities to assess
      the factors regulating urbanisation rates, and how the composition of urban
      assemblages develops as a result. These are major issues for urban ecology.

PMID- 20128786
TI  - Lipoedema: from clinical presentation to therapy. Further aspects.

PMID- 20128787
TI  - Short-term isotretinoin treatment decreases insulin-like growth factor-1 and
      insulin-like growth factor binding protein-3 levels: does isotretinoin affect
      growth hormone physiology?
AB  - BACKGROUND: Isotretinoin is an effective treatment for acne vulgaris. However, it
      has numerous side-effects. It was previously reported that serum growth hormone
      (GH) levels decreased with isotretinoin treatment. OBJECTIVES: To analyse whether
      isotretinoin has any effects on insulin-like growth factor-1 (IGF-1), insulin
      like growth factor binding protein-3 (IGFBP3) and GH levels. METHODS: Forty-seven
      patients aged 21.5 +/- 5.1 years (mean +/- SD) with acne vulgaris were included
      in this study. Isotretinoin therapy was initiated at a dose of 0.5-0.75 mg kg(-1)
      daily and then adjusted to 0.88 mg kg(-1) daily as maintenance dosage after 1
      month. Screening for biochemical and hormonal parameters was performed just
      before initiation and after 3 months of isotretinoin treatment. RESULTS: IGF-1
      and IGFBP3 levels decreased significantly after treatment (P < 0.01), while GH
      levels did not change. Post-treatment, significant increases were seen in
      aspartate aminotransferase, total cholesterol, low-density lipoprotein
      cholesterol, triglycerides and low-density lipoprotein cholesterol/high-density
      lipoprotein cholesterol ratio (P < 0.0001) while high-density lipoprotein
      cholesterol levels were significantly decreased (P < 0.0001). CONCLUSIONS:
      Isotretinoin therapy may have an effect on GH physiology, and further studies are
      needed to understand this association.

PMID- 20128788
TI  - Epidermolysis bullosa simplex due to KRT5 mutations: mutation-related differences
      in cellular fragility and the protective effects of trimethylamine N-oxide in
      cultured primary keratinocytes.
AB  - BACKGROUND: Epidermolysis bullosa simplex (EBS) is a mechanobullous skin
      fragility disease characterized by cytolysis of basal keratinocytes and
      intraepidermal blistering often caused by mutations in keratin genes (KRT5 or
      KRT14). No remedies exist for these disorders presenting a need for development
      of novel therapies. OBJECTIVES: To identify new genotype-phenotype relationships
      in vivo and in cultured primary EBS keratinocytes in vitro, and to study the
      cytoskeletal stabilizing effects of trimethylamine N-oxide (TMAO) in heat
      stressed EBS cells. METHODS: Genomic DNA and cDNA samples from three Swedish
      patients with EBS were analysed for keratin mutations. Primary EBS keratinocyte
      cultures were established, heat stressed with and without added TMAO, followed by
      evaluation of cellular fragility. RESULTS: In addition to the previously reported
      KRT5 mutation (V186L) in one patient, two patients were found to have a novel
      I183M and recurrent E475G replacements in KRT5. Cultured EBS keratinocytes did
      not exhibit keratin aggregates or cell loss, except in the patient with the
      p.I183M mutation who showed 3% aggregates and 2% cell loss. Upon transient heat
      stress the number of aggregate-containing cells increased to 21%, 27% and 13%,
      respectively, in the p.I183M, p.E475G and p.V186L mutant cells. Interestingly,
      pretreatment with TMAO prior to heat stress, dose dependently reduced the number
      of aggregate-containing cells and cell loss. CONCLUSION: These results revealed a
      genotype-phenotype correlation in EBS keratinocytes upon heat stress and suggest
      protein stabilization as a new therapeutic strategy.

PMID- 20128789
TI  - Frontal fibrosing alopecia in two sisters.

PMID- 20128790
TI  - Is antitumour necrosis factor therapy combined with ultraviolet B phototherapy
      safe?

PMID- 20128791
TI  - Interleukin-1 from epithelial cells fosters T cell-dependent skin inflammation.
AB  - BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis and
      psoriasis are characterized by the infiltration of lymphocytes into the epidermal
      compartment. Several studies point to an active role of skin epithelial cells in
      the pathophysiology of such diseases. OBJECTIVES: In this study we addressed the
      regulatory function of primary human keratinocytes in the interaction with
      autologous T cells and monocytes. METHODS: We used a human coculture model with
      keratinocytes grown from epidermal stem cells of the outer root sheath of human
      hair follicles and autologous T cells. RESULTS: In our coculture system we
      observed a high production of interferon (IFN)-gamma, but not Th2 cytokines, in
      the presence of superantigen or antigen-pulsed autologous monocytes. Critical
      parameters for this effect were: (i) T-cell receptor activation, (ii) an
      intercellular adhesion molecule-1/lymphocyte function-associated antigen (LFA)-1
      dependent interaction between keratinocytes and T cells, and (iii) secretion of
      interleukin (IL)-1beta. Remarkably, in the presence of activated T cells,
      epithelial cells seemed to be a more significant source of IL-1beta than
      monocytes. Application of the LFA-1 blocker efalizumab or IL-1 receptor
      antagonist anakinra enabled us to suppress completely the production of IFN-gamma
      by T cells in the coculture. CONCLUSIONS: IL-1 secretion and the physical contact
      between keratinocytes and activated, infiltrating T cells may be central for the
      development of chronic inflammatory skin conditions.

PMID- 20128792
TI  - Female pattern hair loss in complete androgen insensitivity syndrome.
AB  - Female pattern hair loss, also known as female androgenetic alopecia, is
      generally regarded as an androgen-dependent disorder representing the female
      counterpart of male balding. We describe female pattern hair loss occurring in a
      patient with complete androgen insensitivity syndrome suggesting that mechanisms
      other than direct androgen action contribute to this common form of hair loss in
      women.

PMID- 20128793
TI  - Comparative proteomic analysis between normal skin and keloid scar.
AB  - BACKGROUND: Keloids are pathological scars and, despite numerous available
      treatment modalities, continue to plague physicians and patients. OBJECTIVES:
      Identification of molecular mediators that contribute to this fibrotic phenotype.
      METHODS: Two-dimensional gel electrophoresis, MALDI-TOF, Mascot online database
      searching algorithm and Melanie 5 gel analysis software were employed for
      comparative proteomic analysis between normal skin (NS) and keloid scar (KS)
      tissue extracts. RESULTS: Seventy-nine protein spots corresponding to 23 and 32
      differentially expressed proteins were identified in NS and KS, respectively.
      Isoforms of heat shock proteins, gelsolin, carbonic anhydrase and notably keratin
      10 were strongly expressed in NS along with manganese superoxide dismutase,
      immune components, antitrypsin, prostatic binding protein and crystalline.
      Various classes of proteins were found either to be present or to be upregulated
      in keloid tissue: (i) inflammatory/differentiated keratinocyte markers: S100
      proteins, peroxiredoxin I; (ii) wound healing proteins: gelsolin-like capping
      protein; (iii) fibrogenetic proteins: mast cell beta-tryptase, macrophage
      migration inhibitory factor (MIF); (iv) antifibrotic proteins: asporin; (v)
      tumour suppressor proteins: stratifin, galectin-1, maspin; and (vi)
      antiangiogenic proteins: pigment epithelium-derived factor. Significant increases
      in expression of asporin, stratifin, galectin-1 and MIF were observed by Western
      blot analysis in KS. CONCLUSIONS: This work has identified differentially
      expressed proteins specific to KS tissue extracts which can potentially be used
      as specific targets for therapeutic intervention.

PMID- 20128794
TI  - Clinical guidelines for testing for heritable thrombophilia.

PMID- 20128795
TI  - Whole-body magnetic resonance imaging, including diffusion-weighted imaging, for
      diagnosing bone marrow involvement in malignant lymphoma.

PMID- 20128796
TI  - Microsomal prostaglandin E synthase-1 and cyclooxygenase-2 are both required for
      ischaemic excitotoxicity.
AB  - BACKGROUND AND PURPOSE: Although both microsomal prostaglandin E synthase (mPGES)
      1 and cyclooxygenase (COX)-2 are critical factors in stroke injury, but the
      interactions between these enzymes in the ischaemic brain is still obscure. This
      study examines the hypothesis that mPGES-1 activity is required for COX-2 to
      cause neuronal damage in ischaemic injury. EXPERIMENTAL APPROACH: We used a
      glutamate-induced excitotoxicity model in cultures of rat or mouse hippocampal
      slices and a mouse middle cerebral artery occlusion-reperfusion model in vivo.
      The effect of a COX-2 inhibitor on neuronal damage in mPGES-1 knockout (KO) mice
      was compared with that in wild-type (WT) mice. KEY RESULTS: In rat hippocampal
      slices, glutamate-induced excitotoxicity, as well as prostaglandin (PG) E(2)
      production and PGES activation, was significantly attenuated by either MK-886 or
      NS-398, inhibitors of mPGES-1 and COX-2 respectively; however, co-application of
      these inhibitors had neither an additive nor a synergistic effect. The protective
      effect of NS-398 on the excitotoxicity observed in WT slices was completely
      abolished in mPGES-1 KO slices, which showed less excitotoxicity than WT slices.
      In the transient focal ischaemia model, mPGES-1 and COX-2 were co-localized in
      the infarct region of the cortex. Injection of NS-398 reduced not only ischaemic
      PGE(2) production, but also ischaemic injuries in WT mice, but not in mPGES-1 KO
      mice, which showed less dysfunction than WT mice. CONCLUSION AND IMPLICATIONS:
      Microsomal prostaglandin E synthase-1 and COX-2 are co-induced by excess
      glutamate in ischaemic brain. These enzymes are co-localized and act together to
      exacerbate stroke injury, by excessive PGE(2) production.

PMID- 20128797
TI  - Beneficial effect of the oligomerized polyphenol oligonol on high glucose-induced
      changes in eNOS phosphorylation and dephosphorylation in endothelial cells.
AB  - BACKGROUND AND PURPOSE: Hyperglycaemia is known to reduce nitric oxide (NO)
      bioavailability by modulating endothelial NO synthase (eNOS) activity, and
      polyphenols are believed to have cardiovascular benefit. One possible mechanism
      could be through interaction with eNOS. EXPERIMENTAL APPROACH: The effects of the
      oligomerized polyphenol oligonol on eNOS phosphorylation status and activity were
      examined in porcine aortic endothelial cells cultured in high glucose
      concentrations. KEY RESULTS: Exposure to high glucose concentrations strongly
      inhibited eNOS phosphorylation at Ser-1177 and dephosphorylation at Thr-495 in
      bradykinin (BK)-stimulated cells. These inhibitory effects of high glucose were
      significantly prevented by treatment with oligonol. Akt and p38 mitogen-activated
      protein kinase (MAPK) were activated in BK-stimulated cells. High glucose
      inhibited Akt activation but enhanced p38 MAPK activation, both of which were
      reversed by oligonol treatment. The phosphatidylinositol 3-kinase inhibitor
      wortmannin blocked the reversal by oligonol of phosphorylation at Ser-1177, but
      not dephosphorylation at Thr-495, in BK-stimulated cells exposed to high glucose.
      The effect of oligonol on BK dephosphorylation under high glucose was mimicked by
      protein kinase C (PKC) epsilon-neutralizing peptides. These data suggest that the
      effects of oligonol on high glucose-induced attenuation of eNOS Ser-1177
      phosphorylation and Thr-495 dephosphorylation may be regulated by Akt activation
      and PKCepsilon inhibition respectively. Oligonol also prevented high glucose
      induced attenuation of BK-stimulated NO production. CONCLUSIONS AND IMPLICATIONS:
      Oligonol prevented the impairment of eNOS activity induced by high glucose
      through reversing altered eNOS phosphorylation status. This mechanism may
      underlie the beneficial cardiovascular health effects of this oligomerized
      polyphenol.

PMID- 20128798
TI  - Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice
      via 5-HT1A receptor activation.
AB  - BACKGROUND AND PURPOSE: We aimed to demonstrate the involvement of 5-HT(1A)
      receptors in the therapeutic effect of cannabidiol, a non-psychoactive
      constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by
      bile-duct ligation (BDL) in mice. EXPERIMENTAL APPROACH: Cannabidiol (5 mg x kg(
      1); i.p.) was administered over 4 weeks to BDL mice. Cognition and locomotion
      were evaluated using the eight-arm maze and the open field tests respectively.
      Hippocampi were analysed by RT-PCR for expression of the genes for tumour
      necrosis factor-alpha receptor 1, brain-derived neurotrophic factor (BDNF) and 5
      HT(1A) receptor. N-(2-(4-(2-methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl)
      cyclohexanecarboxamide (WAY-100635), a 5-HT(1A) receptor antagonist (0.5 mg x kg(
      1)), was co-administered with cannabidiol. Liver function was evaluated by
      measuring plasma liver enzymes and bilirubin. KEY RESULTS: Cannabidiol improved
      cognition and locomotion, which were impaired by BDL, and restored hippocampal
      expression of the tumour necrosis factor-alpha receptor 1 and the BDNF genes,
      which increased and decreased, respectively, following BDL. It did not affect
      reduced 5-HT(1A) expression in BDL mice. All the effects of cannabidiol, except
      for that on BDNF expression, were blocked by WAY-100635, indicating 5-HT(1A)
      receptor involvement in cannabidiol's effects. Cannabidiol did not affect the
      impaired liver function in BDL. CONCLUSIONS AND IMPLICATIONS: The behavioural
      outcomes of BDL result from both 5-HT(1A) receptor down-regulation and
      neuroinflammation. Cannabidiol reverses these effects through a combination of
      anti-inflammatory activity and activation of this receptor, leading to
      improvement of the neurological deficits without affecting 5-HT(1A) receptor
      expression or liver function. BDNF up-regulation by cannabidiol does not seem to
      account for the cognitive improvement.

PMID- 20128799
TI  - Substance P and glutamate receptor antagonists improve the anti-arthritic actions
      of dexamethasone in rats.
AB  - BACKGROUND AND PURPOSE: Current single drug treatments for rheumatoid arthritis
      have problems of limited efficacy and/or high toxicity. This study investigates
      the benefits of individual and combined treatments with dexamethasone and
      substance P and glutamate receptor antagonists in a rat model of arthritis.
      EXPERIMENTAL APPROACH: Arthritis was induced in rats by unilateral intra
      articular injection of Freund's complete adjuvant. Separate groups of rats were
      subjected to the following treatments 15 min before induction of arthritis: (i)
      control with no drug treatment; (ii) single intra-articular injection of a NK(1)
      receptor antagonist RP67580; (iii) single intra-articular injection of a NMDA
      receptor antagonist AP7 plus a non-NMDA receptor antagonist CNQX; (iv) daily oral
      dexamethasone; and (v) combined treatment with dexamethasone and all of the above
      receptor antagonists. Knee joint allodynia, swelling, hyperaemia and histological
      changes were examined over a period of 7 days. KEY RESULTS: Treatment with
      dexamethasone suppressed joint swelling, hyperaemia and histological changes that
      include polymorphonuclear cell infiltration, synovial tissue proliferation and
      cartilage erosion in the arthritic rat knees. Treatment with RP67580 or AP7 plus
      CNQX did not attenuate hyperaemia or histological changes, but reduced joint
      allodynia and swelling. Co-administration of dexamethasone with these receptor
      antagonists produced greater inhibition on joint allodynia and swelling than
      their individual effects. CONCLUSIONS AND IMPLICATIONS: The data suggest
      substance P and glutamate contribute to arthritic pain and joint swelling. The
      efficacy of dexamethasone in reducing arthritic pain and joint swelling can be
      improved by co-administration of substance P and glutamate receptor antagonists.

PMID- 20128800
TI  - Glucagon-like peptide 1 receptor stimulation as a means of neuroprotection.
AB  - Glucagon-like peptide 1 (GLP-1) is a relatively recently discovered molecule
      originating in the so-called L-cells of the intestine. The peptide has
      insulinotrophic properties and it is this characteristic that has predominantly
      been investigated. This has led to the use of the GLP-1-like peptide exendin-4
      (EX-4), which has a much longer plasma half-life than GLP-1 itself, being used in
      the treatment of type II diabetes. The mode of action of this effect appears to
      be a reduction in pancreatic apoptosis, an increase in beta cell proliferation or
      both. Thus, the effects of GLP-1 receptor stimulation are not based upon insulin
      replacement but an apparent repair of the pancreas. Similar data suggest that the
      same effects may occur in other peripheral tissues. More recently, the roles of
      GLP-1 and EX-4 have been studied in nervous tissue. As in the periphery, both
      peptides appear to promote cellular growth and reduce apoptosis. In models of
      Alzheimer's disease, Parkinson's disease and peripheral neuropathy, stimulation
      of the GLP-1 receptor has proved to be highly beneficial. In the case of
      Parkinson's disease this effect is evident after the neurotoxic lesion is
      established, suggesting real potential for therapeutic use. In the present review
      we examine the current status of the GLP-1 receptor and its potential as a
      therapeutic target.

PMID- 20128801
TI  - Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear
      factor-kappaB and inhibiting mitogen-activated protein kinases.
AB  - BACKGROUND AND PURPOSE: Cilostazol is a specific inhibitor of 3'-5'-cyclic
      adenosine monophosphate (cAMP) phosphodiesterase, which is widely used to treat
      ischemic symptoms of peripheral vascular disease. Although cilostazol has been
      shown to exhibit vasodilator properties as well as antiplatelet and anti
      inflammatory effects, its cellular mechanism in microglia is unknown. In the
      present study, we assessed the anti-inflammatory effect of cilostazol on the
      production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated
      murine BV2 microglia. EXPERIMENTAL APPROACH: We examined the effects of
      cilostazol on LPS-induced nuclear factor-kappaB (NF-kappaB) activation and
      phosphorylation of mitogen-activated protein kinases (MAPKs). KEY RESULTS:
      Cilostazol suppressed production of nitric oxide (NO), prostaglandin E(2)
      (PGE(2)) and the proinflammatory cytokines, interleukin-1 (IL-1), tumour necrosis
      factor-alpha, and monocyte chemoattractant protein-1 (MCP-1), in a concentration
      dependent manner. Inhibitory effects of cilostazol were not affected by treatment
      with an adenylate cyclase inhibitor, SQ 22536, indicating that these actions of
      cilostazol were cAMP-independent. Cilostazol significantly inhibited the DNA
      binding and transcriptional activity of NF-kappaB. Moreover, cilostazol blocked
      signalling upstream of NF-kappaB activation by inhibiting extracellular signal
      regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK), but without
      affecting the activity of p38 MAPK. CONCLUSION AND IMPLICATIONS: Our results
      demonstrate that suppression of the NF-kappaB, ERK, JNK signalling pathways may
      inhibit LPS-induced NO and PGE(2) production. Therefore, cilostazol may have
      therapeutic potential for neurodegenerative diseases by inhibiting pro
      inflammatory mediators and cytokine production in activated microglia.

PMID- 20128802
TI  - Oxaliplatin responses in colorectal cancer cells are modulated by CHK2 kinase
      inhibitors.
AB  - BACKGROUND AND PURPOSE: Checkpoint kinase 2 (CHK2) is activated by DNA damage and
      can contribute to p53 stabilization, modulating growth arrest and/or apoptosis.
      We investigated the contribution of CHK2 to oxaliplatin-mediated toxicity in a
      colorectal cancer model. EXPERIMENTAL APPROACH: We evaluated the ability of CHK2
      small molecule inhibitors to potentiate oxaliplatin-induced toxicity. The role of
      CHK2 in oxaliplatin-induced apoptosis was investigated in HCT116 cells that were
      wild-type (WT) or KO for CHK2. Small molecule inhibitors of CHK2 were used in
      combination studies with oxaliplatin in this cell model. KEY RESULTS: In
      oxaliplatin-treated CHK2 KO cells, accelerated apoptosis was accompanied by
      attenuated p53 stabilization and p21(WAF-1) up-regulation correlating with
      increased Bax expression, cytochrome c release and elevated caspase activity. The
      higher levels of apoptosis in CHK2 KO cells were restored to control (WT) levels
      when CHK2 was re-introduced. This 'uncoupling' of p53 stabilization and Bax up
      regulation in CHK2 KO cells suggested oxaliplatin-induced apoptosis was due to a
      p53-independent response. Combination studies revealed that CHK2 inhibitor II or
      debromohymenialdisine antagonized the responses to oxaliplatin. This inhibitory
      effect correlated with decreases in apoptosis, p53 stabilization and DNA inter
      strand cross-link formation, and was dependent on the presence (but not activity)
      of CHK2. CONCLUSIONS AND IMPLICATIONS: Combinations of CHK2 inhibitors with
      oxaliplatin should further sensitize cells to oxaliplatin treatment. However,
      these inhibitors produced an antagonistic effect on the response to oxaliplatin,
      which was reversed on the re-introduction of CHK2. These observations may have
      implications for the use of oxaliplatin in colorectal cancer therapy in
      combination with therapies targeting CHK2.

PMID- 20128803
TI  - Deletion of the distal COOH-terminus of the A2B adenosine receptor switches
      internalization to an arrestin- and clathrin-independent pathway and inhibits
      recycling.
AB  - BACKGROUND AND PURPOSE: We have investigated the effect of deletions of a
      postsynaptic density, disc large and zo-1 protein (PDZ) motif at the end of the
      COOH-terminus of the rat A(2B) adenosine receptor on intracellular trafficking
      following long-term exposure to the agonist 5'-(N-ethylcarboxamido)-adenosine.
      EXPERIMENTAL APPROACH: The trafficking of the wild type A(2B) adenosine receptor
      and deletion mutants expressed in Chinese hamster ovary cells was studied using
      an enzyme-linked immunosorbent assay in combination with immunofluorescence
      microscopy. KEY RESULTS: The wild type A(2B) adenosine receptor and deletion
      mutants were all extensively internalized following prolonged treatment with
      NECA. The intracellular compartment through which the Gln(325)-stop receptor
      mutant, which lacks the Type II PDZ motif found in the wild type receptor
      initially trafficked was not the same as the wild type receptor. Expression of
      dominant negative mutants of arrestin-2, dynamin or Eps-15 inhibited
      internalization of wild type and Leu(330)-stop receptors, whereas only dominant
      negative mutant dynamin inhibited agonist-induced internalization of Gln(325)
      stop, Ser(326)-stop and Phe(328)-stop receptors. Following internalization, the
      wild type A(2B) adenosine receptor recycled rapidly to the cell surface, whereas
      the Gln(325)-stop receptor did not recycle. CONCLUSIONS AND IMPLICATIONS:
      Deletion of the COOH-terminus of the A(2B) adenosine receptor beyond Leu(330)
      switches internalization from an arrestin- and clathrin-dependent pathway to one
      that is dynamin dependent but arrestin and clathrin independent. The presence of
      a Type II PDZ motif appears to be essential for arrestin- and clathrin-dependent
      internalization, as well as recycling of the A(2B) adenosine receptor following
      prolonged agonist addition.

PMID- 20128804
TI  - Thrombin activation of proteinase-activated receptor 1 potentiates the
      myofilament Ca2+ sensitivity and induces vasoconstriction in porcine pulmonary
      arteries.
AB  - BACKGROUND AND PURPOSE: Thrombus formation is commonly associated with pulmonary
      arterial hypertension (PAH). Thrombin may thus play an important role in the
      pathogenesis and pathophysiology of PAH. Hence, we investigated the contractile
      effects of thrombin and its mechanism in pulmonary artery. EXPERIMENTAL APPROACH:
      The cytosolic Ca(2+) concentrations ([Ca(2+)](i)), 20 kDa myosin light chain
      (MLC20) phosphorylation and tension development were evaluated using the isolated
      porcine pulmonary artery. KEY RESULTS: Thrombin induced a sustained contraction
      in endothelium-denuded strips obtained from different sites of a pulmonary
      artery, ranging from the main pulmonary artery to the intrapulmonary artery. In
      the presence of endothelium, thrombin induced a transient relaxation. The
      contractile effect of thrombin was abolished by either a protease inhibitor or a
      proteinase-activated receptor 1 (PAR(1)) antagonist, while it was mimicked by
      PAR(1)-activating peptide (PAR(1)AP), but not PAR(4)AP. The thrombin-induced
      contraction was associated with a small elevation of [Ca(2+)](i) and an increase
      in MLC20 phosphorylation. Thrombin and PAR(1)AP induced a greater increase in
      tension for a given [Ca(2+)](i) elevation than that obtained with high K(+)
      depolarization. They also induced a contraction at a fixed Ca(2+) concentration
      in alpha-toxin-permeabilized preparations. CONCLUSIONS AND IMPLICATIONS: The
      present study revealed a unique property of the pulmonary artery. In contrast to
      normal arteries of the systemic circulation, thrombin induces a sustained
      contraction in the normal pulmonary artery, by activating PAR(1) and thereby
      increasing the sensitivity of the myofilament to Ca(2+). This responsiveness of
      the pulmonary artery to thrombin may therefore contribute to the pathogenesis and
      pathophysiology of PAH.

PMID- 20128805
TI  - Pharmacological stimulation and inhibition of insulin secretion in mouse islets
      lacking ATP-sensitive K+ channels.
AB  - BACKGROUND AND PURPOSE: ATP-sensitive potassium channels (K(ATP) channels) in
      beta cells are a major target for insulinotropic drugs. Here, we studied the
      effects of selected stimulatory and inhibitory pharmacological agents in islets
      lacking K(ATP) channels. EXPERIMENTAL APPROACH: We compared insulin secretion
      (IS) and cytosolic calcium ([Ca(2+)](c)) changes in islets isolated from control
      mice and mice lacking sulphonylurea receptor1 (SUR1), and thus K(ATP) channels in
      their beta cells (Sur1KO). KEY RESULTS: While similarly increasing [Ca(2+)](c)
      and IS in controls, agents binding to site A (tolbutamide) or site B
      (meglitinide) of SUR1 were ineffective in Sur1KO islets. Of two non-selective
      blockers of potassium channels, quinine was inactive, whereas tetraethylammonium
      was more active in Sur1KO compared with control islets. Phentolamine, efaroxan
      and alinidine, three imidazolines binding to K(IR)6.2 (pore of K(ATP) channels),
      stimulated control islets, but only phentolamine retained weaker stimulatory
      effects on [Ca(2+)](c) and IS in Sur1KO islets. Neither K(ATP) channel opener
      (diazoxide, pinacidil) inhibited Sur1KO islets. Calcium channel blockers
      (nimodipine, verapamil) or diphenylhydantoin decreased [Ca(2+)](c) and IS in both
      types of islets, verapamil and diphenylhydantoin being more efficient in Sur1KO
      islets. Activation of alpha(2)-adrenoceptors or dopamine receptors strongly
      inhibited IS while partially (clonidine > dopamine) lowering [Ca(2+)](c) (control
      > Sur1KO islets). CONCLUSIONS AND IMPLICATIONS: Those drugs retaining effects on
      IS in islets lacking K(ATP) channels, also affected [Ca(2+)](c), indicating
      actions on other ionic channels. The greater effects of some inhibitors in Sur1KO
      than in control islets might be relevant to medical treatment of congenital
      hyperinsulinism caused by inactivating mutations of K(ATP) channels.

PMID- 20128806
TI  - Lack of effect of the alpha2C-adrenoceptor Del322-325 polymorphism on inhibition
      of cyclic AMP production in HEK293 cells.
AB  - BACKGROUND AND PURPOSE: The alpha(2C)-adrenoceptor has multiple functions,
      including inhibiting release of noradrenaline from presynaptic nerve terminals. A
      human alpha(2C) polymorphism, Del322-325, a potential risk factor for heart
      failure, has been reported to exhibit reduced signalling in CHO cells. To further
      understand the role of the Del322-325 polymorphism on receptor signalling, we
      attempted to replicate and further study the reduced signalling in HEK293 cells.
      EXPERIMENTAL APPROACH: Human alpha(2C) wild-type (WT) and Del322-325
      adrenoceptors were stably transfected into HEK293 cells. Radioligand binding was
      performed to determine affinities for both receptors. In intact cells, inhibition
      of forskolin-stimulated cyclic AMP production by WT and Del322-325 clones with a
      range of receptor densities (200-2320 fmol.mg(-1) protein) was measured following
      agonist treatment. KEY RESULTS: Noradrenaline, brimonidine and clonidine
      exhibited similar binding affinities for WT and Del322-325. Brimonidine and
      clonidine also had similar efficacies and potencies for both receptors for the
      inhibition of cyclic AMP production at all receptor densities tested. A linear
      regression analysis comparing efficacy and potency with receptor expression
      levels showed no differences in slopes between WT and Del322-325. CONCLUSIONS AND
      IMPLICATIONS: The alpha(2C) WT and Del322-325 adrenoceptors exhibited similar
      binding properties. Additionally, inhibition of cyclic AMP production by Del322
      325 was similar to that of WT over a range of receptor densities. Therefore, in
      intact HEK293 cells, the alpha(2C)-Del322-325 polymorphism does not exhibit
      reduced signalling to adenylyl cyclase and may not represent a clinically
      important phenotype.

PMID- 20128807
TI  - SZ-685C, a marine anthraquinone, is a potent inducer of apoptosis with anticancer
      activity by suppression of the Akt/FOXO pathway.
AB  - BACKGROUND AND PURPOSE: The aims of this study were to investigate the anti
      cancer activity of SZ-685C, an anthracycline analogue isolated from marine
      derived mangrove endophytic fungi, and to explore the molecular mechanisms
      underlying such activity. EXPERIMENTAL APPROACH: The effect of SZ-685C on the
      viability of cancer cell lines was investigated using the 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. SZ-685C-induced apoptosis was
      assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining,
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay and
      analysis of caspase activation. The effect of SZ-685C on the Akt/FOXO pathway was
      studied using Western blotting analysis, and the in vivo anti-tumour efficacy was
      examined in an MDA-MB-435 breast cancer xenograft model. KEY RESULTS: SZ-685C
      suppressed the proliferation of six cancer cell lines derived from human breast
      cancer, prostate cancer, glioma and hepatoma (IC(50) values ranged from 3.0 to
      9.6 microM) and the growth of breast cancer xenografts in mice. SZ-685C had a
      direct apoptosis-inducing effect through both the extrinsic and intrinsic
      apoptotic pathways, as shown by activation of caspase-8 and 9 as well as effector
      caspase-3 and poly (ADP-ribose) polymerase. Phosphorylation of Akt and its
      downstream effectors, forkhead box protein O1 and forkhead box protein O3a, was
      down-regulated in SZ-685C-treated cancer cells. Furthermore, the pro-apoptotic
      protein Bim was up-regulated by SZ-685C treatment consistent with FOXO
      dephosphorylation. CONCLUSIONS AND IMPLICATIONS: SZ-685C could induce apoptosis
      through the Akt/FOXO pathway, which consequently leads to the observed anti
      tumour effect both in vitro and in vivo. Our data suggest that SZ-685C may be a
      potentially promising Akt inhibitor and anti-cancer drug candidate.

PMID- 20128808
TI  - Stimulation of angiotensin AT2 receptors by the non-peptide agonist, Compound 21,
      evokes vasodepressor effects in conscious spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Angiotensin type 2 receptor (AT(2) receptor) stimulation
      evokes vasodilator effects in vitro and in vivo that oppose the vasoconstrictor
      effects of angiotensin type 1 receptors (AT(1) receptors). Recently, a novel non
      peptide AT(2) receptor agonist, Compound 21, was described, which exhibited high
      AT(2) receptor selectivity. EXPERIMENTAL APPROACH: Functional cardiovascular
      effects of the drug candidate Compound 21 were assessed, using mouse isolated
      aorta and rat mesenteric arteries in vitro and in conscious spontaneously
      hypertensive rats (SHR). KEY RESULTS: Compound 21 evoked dose-dependent
      vasorelaxations in aortic and mesenteric vessels, abolished by the AT(2) receptor
      antagonist, PD123319. In vivo, Compound 21 administered alone, at doses ranging
      from 50 to 1000 ng.kg(-1).min(-1) over 4 h did not decrease blood pressure in
      conscious normotensive Wistar-Kyoto rats or SHR. However, when given in
      combination with the AT(1) receptor antagonist, candesartan, Compound 21 (300
      ng.kg(-1).min(-1)) lowered blood pressure in SHR only. Further analysis in
      separate groups of conscious SHR revealed that, at a sixfold lower dose, Compound
      21 (50 ng.kg(-1).min(-1)) still evoked a significant depressor response in adult
      SHR ( approximately 30 mmHg) when combined with different doses of candesartan
      (0.01 or 0.1 mg.kg(-1)). Moreover, the Compound 21-evoked depressor effect was
      abolished when co-infused (50 microg.kg(-1).min(-1) for 2 h) with the AT(2)
      receptor antagonist PD123319. CONCLUSION AND IMPLICATIONS: Collectively, our
      results indicate that acute administration of Compound 21 evoked blood pressure
      reductions via AT(2) receptor stimulation. Thus Compound 21 can be considered an
      excellent drug candidate for further study of AT(2) receptor function in
      cardiovascular disease.

PMID- 20128809
TI  - Delta-aminolevulinic acid is a substrate for the amino acid transporter SLC36A1
      (hPAT1).
AB  - BACKGROUND AND PURPOSE: delta-Aminolevulinic acid (ALA) is used in cancer
      patients for photodynamic diagnosis or therapy. Oral administration of ALA has
      been used in patients with prostate and bladder cancer. The present aim was to
      investigate the mechanism of intestinal absorption of ALA and its transport via
      the amino acid transporter SLC36A1. EXPERIMENTAL APPROACH: In vitro
      investigations of ALA affinity for and uptake via SLC36A1 and SLC15A1 were
      performed in Caco-2 cell monolayers. Interaction of ALA with SLC15A1 was
      investigated in MDCK/SLC15A1 cells, whereas interactions with SLC36A1 were
      investigated in COS-7 cells transiently expressing SLC36A1. KEY RESULTS: ALA
      inhibited SLC36A1-mediated L-[(3)H]Pro and SLC15A1-mediated [(14)C]Gly-Sar uptake
      in Caco-2 cell monolayers with IC(50) values of 11.3 and 2.1 mM respectively. In
      SLC36A1-expressing COS-7 cells, the uptake of [(14)C]ALA was saturable with a
      K(m) value of 6.8 +/- 3.0 mM and a V(max) of 96 +/- 13 pmol x cm(-2) x min(-1).
      Uptake of [(14)C]ALA was pH and concentration dependent, and could be inhibited
      by glycine, proline and GABA. In a membrane potential assay, translocation of ALA
      via SLC36A1 was concentration dependent, with a K(m) value of 3.8 +/- 1.0 mM. ALA
      is thus a substrate for SLC36A1. In Caco-2 cells, apical [(14)C]ALA uptake was pH
      dependent, but Na(+) independent, and completely inhibited by 5-hydroxy-L
      tryptophan and L-4,4'-biphenylalanyl-l-proline. CONCLUSIONS AND IMPLICATIONS. ALA
      was a substrate for SLC36A1, and the apical absorption in Caco-2 cell was only
      mediated by SLC36A1 and SLC15A1. This advances our understanding of intestinal
      absorption mechanisms of ALA, as well as its potential for drug interactions.

PMID- 20128810
TI  - The effect of tyrosine nitration of L-type Ca2+ channels on excitation
      transcription coupling in colonic inflammation.
AB  - BACKGROUND AND PURPOSE: Excitation-transcriptional coupling involves
      communication between plasma membrane ion channels and gene expression in the
      nucleus. Calcium influx through L-type Ca(2+) channels induces phosphorylation of
      the transcription factor, cyclic-AMP response element binding protein (CREB) and
      downstream activation of the cyclic-AMP response element (CRE) promoter regions.
      Tyrosine nitration of Ca(2+) channels attenuates interactions with c-Src kinase,
      decreasing Ca(2+) channel currents and smooth muscle contraction during colonic
      inflammation. In this study we examined the effect of tyrosine nitration and
      colonic inflammation on Ca(2+) channel mediated phosphorylation of CREB and CRE
      activation. EXPERIMENTAL APPROACH: CREB and phospho-CREB were detected by Western
      blots and CRE activation measured by dual luciferase assay. Chinese hamster ovary
      (CHO) cells were transfected with hCa(v)1.2b and hCa(v)1.2b c-terminal mutants.
      Colonic inflammation was induced by intracolonic instillation of 2,4,6
      trinitrobenzene sulphonic acid in mouse colon. KEY RESULTS: In hCa(v)1.2b
      transfected CHO cells and in native colonic smooth muscle, depolarization with 80
      mM KCl induced CREB phosphorylation (pCREB). Treatment with peroxynitrite
      inhibited KCl-induced pCREB. Following experimental colitis, KCl-induced CREB
      phosphorylation was abolished in smooth muscle, concomitant with tyrosine
      nitration of Ca(2+) channels. Depolarization increased CRE activation in
      hCa(v)1.2b CHO cells by 2.35 fold which was blocked by nifedipine and by protein
      nitration of Ca(2+) channels with peroxynitrite. The Src-kinase inhibitor, PP2,
      blocked depolarization-induced CRE activation. Mutation of the C-terminus
      tyrosine residue, Y2134F, but not Y1861F, blocked CRE activation. CONCLUSIONS AND
      IMPLICATIONS: Post-translational modification of Ca(2+) channels due to tyrosine
      nitration modified excitation-transcriptional coupling in colonic inflammation.

PMID- 20128811
TI  - Icariin protects against bone loss induced by oestrogen deficiency and activates
      oestrogen receptor-dependent osteoblastic functions in UMR 106 cells.
AB  - BACKGROUND AND PURPOSE: Icariin may be the active ingredient in Herba Epimedii, a
      Chinese herb commonly used for treatment of osteoporosis. The present study aims
      to delineate the mechanism(s) by which icariin prevents bone loss after
      ovariectomy (OVX) in vivo and stimulates osteoblastic functions in vitro.
      EXPERIMENTAL APPROACH: Ovariectomized or sham-operated C57BL/6 mice were treated
      with vehicle, 17beta-oestradiol or icariin for 6 weeks. Total and trabecular bome
      mineral density (BMD) as well as polar stress-strain index of distal femur were
      measured by peripheral computed tomography. The mRNA expressions of OPG and RANKL
      in tibia were studied by RT-PCR. Interactions between the oestrogen receptor (ER)
      antagonist ICI182,780 and icariin were studied in UMR 106 cells. The functional
      transactivation of ERalpha and ERbeta as well as ERalpha phosphorylation by
      icariin were also assessed. KEY RESULTS: Icariin suppressed the loss of bone mass
      and strength in distal femur and increased the mRNA expression ratio of OPG/RANKL
      in tibia, following OVX. Icariin increased ER-dependent cell proliferation,
      alkaline phosphatase (ALP) activity, gene expression of OPG and the OPG/RANKL
      ratio in UMR 106 cells. Icariin did not activate ERE-luciferase activity in UMR
      106 cells, via the ERalpha or the ERbeta-mediated pathway, but it did increase
      ERalpha phosphorylation at Ser118. CONCLUSIONS AND IMPLICATIONS: Our results
      indicate that icariin exerts anabolic effects in bone possibly by activating ER
      in a ligand-independent manner. Its ability to prevent OVX-induced bone loss
      without inducing uterotrophic effects supports its use as an alternative regimen
      for management of postmenopausal osteoporosis.

PMID- 20128812
TI  - Functional interactions between 5-HT2A and presynaptic 5-HT1A receptor-based
      responses in mice genetically deficient in the serotonin 5-HT transporter (SERT).
AB  - BACKGROUND AND PURPOSE: Despite decreased presynaptic 5-HT(1A) and altered 5
      HT(2A) receptor function in genetically-deficient serotonin (5-HT) transporter
      (SERT) mice, the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100635)
      still induced head twitches in these mice, a well-established 5-HT(2A) receptor
      mediated response. EXPERIMENTAL APPROACH: Interactions between 5-HT(1A) and 5
      HT(2A) receptors were assessed using the head-twitch response following 5-HT(1A)
      and 5-HT(2A) receptor agonists and antagonists in SERT wild-type (+/+),
      heterozygous (+/-), and knockout (-/-) mice. The role of brain 5-HT availability
      in WAY 100635 induced head twitches was also examined. KEY RESULTS: WAY 100635
      induced head twitches in a SERT gene-dose dependent manner, inducing 5-fold more
      head twitches in SERT -/- versus SERT +/+ mice. In SERT -/- mice, inhibition of 5
      HT synthesis with p-chlorophenylalanine (PCPA) markedly depleted tissue 5-HT in
      all five brain areas examined and abolished WAY 100635 induced head twitches.
      Further, the selective 5-HT reuptake inhibitor fluvoxamine increased WAY 100635
      induced head twitches in SERT +/+ and +/- mice. Head twitches following the 5
      HT(2A) receptor agonist (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI)
      were robust in SERT +/+ and +/- mice but much reduced in SERT -/- mice. DOI
      induced head twitches were decreased by the 5-HT(1A) agonist 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) in SERT +/+ and +/- mice. All drug-induced head
      twitches were blocked by the 5-HT(2A) receptor antagonist a-Phenyl-1-(2
      phenylethyl)-4-piperidinemethanol (MDL 11,939). CONCLUSIONS AND IMPLICATIONS:
      These data show that indirect activation of 5-HT(2A) receptors via blockade of
      presynaptic 5-HT(1A) receptors potentiated head-twitch responses, suggesting
      functional interactions between these receptors, interactions affected by altered
      5-HT availability. Our findings strongly support the correlation of WAY 100635
      induced head twitches with increased 5-HT availability, induced genetically or
      pharmacologically.

PMID- 20128813
TI  - Nitric oxide donor trans-[RuCl([15]aneN)NO] as a possible therapeutic approach
      for Chagas' disease.
AB  - BACKGROUND AND PURPOSE: Benznidazole (Bz) is the therapy currently available for
      clinical treatment of Chagas' disease. However, many strains of Trypanosoma cruzi
      parasites are naturally resistant. Nitric oxide (NO) produced by activated
      macrophages is crucial to the intracellular killing of parasites. Here, we
      investigate the in vitro and in vivo activities against T. cruzi, of the NO
      donor, trans-[RuCl([15]aneN(4))NO](2+). EXPERIMENTAL APPROACH: Trans
      [RuCl([15]aneN(4))NO](2+)was incubated with a partially drug-resistant T. cruzi Y
      strain and the anti-proliferative (epimastigote form) and trypanocidal activities
      (trypomastigote and amastigote) evaluated. Mice were treated during the acute
      phase of Chagas' disease. The anti-T. cruzi activity was evaluated by
      parasitaemia, survival rate, cardiac parasitism, myocarditis and the curative
      rate. KEY RESULTS: Trans-[RuCl([15]aneN(4))NO](2+) was 10- and 100-fold more
      active than Bz against amastigotes and trypomastigotes respectively. Further,
      trans-[RuCl([15]aneN(4))NO](2+) (0.1 mM) induced 100% of trypanocidal activity
      (trypomastigotes forms) in vitro. Trans-[RuCl([15]aneN(4))NO](2+) induced
      permanent suppression of parasitaemia and 100% survival in a murine model of
      acute Chagas' disease. When the drugs were given alone, parasitological cures
      were confirmed in only 30 and 40% of the animals treated with the NO donor (3.33
      micromol.kg(-1).day(-1)) and Bz (385 micromol.kg(-1).day(-1)), respectively, but
      when given together, 80% of the animals were parasitologically cured. The cured
      animals showed an absence of myocarditis and a normalisation of cytokine
      production in the sera. In addition, no in vitro toxicity was observed at the
      tested doses. CONCLUSIONS AND IMPLICATIONS: These findings indicate that trans
      [RuCl([15]aneN(4))NO](2+)is a promising lead compound for the treatment of human
      Chagas' disease.

PMID- 20128814
TI  - Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen
      (ATB-346).
AB  - BACKGROUND AND PURPOSE: Hydrogen sulphide is an important mediator of gastric
      mucosal defence. The use of non-steroidal anti-inflammatory drugs continues to be
      limited by their toxicity, particularly in the upper gastrointestinal tract. We
      evaluated the gastrointestinal safety and anti-inflammatory efficacy of a novel
      hydrogen sulphide-releasing derivative of naproxen, ATB-346 [2-(6-methoxy
      napthalen-2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester]. EXPERIMENTAL
      APPROACH: The ability of ATB-346 versus naproxen to cause gastric damage was
      evaluated in healthy rats and in rats with compromised gastric mucosal defence.
      Effects on the small intestine and on the healing of ulcers were also assessed.
      The ability of ATB-346 to inhibit cyclooxygenase-1 and 2 and to reduce
      inflammation in vivo was also evaluated. KEY RESULTS: ATB-346 suppressed gastric
      prostaglandin E(2) synthesis as effectively as naproxen, but produced negligible
      damage in the stomach and intestine. In situations in which the gastric mucosa
      was rendered significantly more susceptible to naproxen-induced damage (e.g.
      ablation of sensory afferent nerves, inhibition of endogenous nitric oxide or
      hydrogen sulphide synthesis, co-administration with aspirin, antagonism of
      K(IR)6.x channels), ATB-346 did not cause significant damage. Unlike naproxen and
      celecoxib, ATB-346 accelerated healing of pre-existing gastric ulcers. In a mouse
      airpouch model, ATB-346 suppressed cyclooxygenase-2 activity and inhibited
      leukocyte infiltration more effectively than naproxen. ATB-346 was as effective
      as naproxen in adjuvant-induced arthritis in rats, with a more rapid onset of
      activity. Unlike naproxen, ATB-346 did not elevate blood pressure in hypertensive
      rats. CONCLUSIONS AND IMPLICATIONS: ATB-346 exhibits anti-inflammatory properties
      similar to naproxen, but with substantially reduced gastrointestinal toxicity.

PMID- 20128815
TI  - The selective beta1-adrenoceptor antagonist nebivolol is a potential oestrogen
      receptor agonist with neuroprotective abilities.
AB  - BACKGROUND AND PURPOSE: Nebivolol, a selective beta(1)-adrenoceptor antagonist
      mediating rapid vasodilating effects, is used clinically to treat hypertension.
      Recently, it was reported that nebivolol also acts as an oestrogen receptor (ER)
      agonist. To investigate the neuroprotective potential of oestrogens, we assessed
      the oestrogenic effects of nebivolol in several in vitro neuronal models.
      EXPERIMENTAL APPROACH: Human neuroepithelioma SK-N-MC cells stably transfected
      with human ER alpha and beta, and mouse N2A neuroblastoma cells expressing human
      APP695(SWE)[N2Aswe, stably transfected with the Swedish mutation form of the
      Alzheimer-associated amyloid precursor protein (APPswe, K670M/N671L)] were
      incubated with different concentrations of nebivolol and 17beta-oestradiol (E2)
      for 24-48 h. ER activation was detected in a specific reporter assay, and ER
      dependent gene expression was measured by quantitative real-time PCR (qRT PCR).
      Furthermore, cell survival rates were determined, and oxidative stress was
      induced by hydrogen peroxide and paraquat. Amyloid beta protein precursor (APP)
      processing was investigated, and the cleavage fragments sAPPalpha and Abeta were
      quantified via alpha-, beta- and gamma-secretase activity assays. Alterations of
      secretase expression levels were determined by qRT PCR. KEY RESULTS: Nebivolol
      induces oestrogen-dependent gene transcription, and protects neuronal cells
      against oxidative stress even at low and physiological concentrations (10(-8) M).
      Moreover, nebivolol modulates processing of APP in mouse neuronal N2Aswe cells by
      increasing alpha-secretase activity, ultimately leading to enhanced release of
      soluble non-amyloidogenic sAPPalpha. CONCLUSIONS AND IMPLICATIONS: We showed that
      nebivolol acts as ER agonist in neuronal cell lines, and suggest oestrogen-like
      neuroprotective effects mediated by nebivolol.

PMID- 20128816
TI  - Activation of cardiac muscarinic M3 receptors induces delayed cardioprotection by
      preserving phosphorylated connexin43 and up-regulating cyclooxygenase-2
      expression.
AB  - BACKGROUND AND PURPOSE: Activation of muscarinic M(3) mucarinic acetylcholine
      receptors (M(3)-mAChRs) has been previously shown to confer short-term
      cardioprotection against ischaemic injuries. However, it is not known whether
      activation of these receptors can provide delayed cardioprotection. Consequently,
      the present study was undertaken to investigate whether stimulation of M(3)
      mAChRs can induce delayed preconditioning in rats, and to characterize the
      potential mechanism. EXPERIMENTAL APPROACH: Rats were pretreated (24 h),
      respectively, with M(3)-mAChRs agonist choline, M(3)-mAChRs antagonist 4-DAMP or
      M(2)-mAChRs antagonist methoctramine followed by the administration of choline.
      This was followed by 30 min of ischaemia and then 3 h of reperfusion. Ischaemia
      induced arrhythmias and ischaemia-reperfusion (I/R)-induced infarction were
      determined. The phosphorylation status of connexin43 (Cx43) after 30 min
      ischaemia, and the expression level of Hsp70, cyclooxygenase-2 (COX-2) and iNOS
      effected by administration of choline were also measured. KEY RESULTS: Compared
      to the control group, pretreatment with choline significantly decreased ischaemia
      induced arrhythmias, reduced the total number of ventricular premature beats, the
      duration of ventricular tachycardia episodes and markedly reduced I/R-induced
      infarct size. Furthermore, choline attenuated ischaemia-induced dephosphorylation
      of Cx43, and up-regulated the expression of Hsp70 and COX-2. Administration of 4
      DAMP abolished these changes, while methoctramine had no effect. CONCLUSIONS AND
      IMPLICATIONS: Our results suggest that stimulation of M(3)-mAChRs with choline
      elicits delayed preconditioning, which we propose is the result of up-regulation
      of the expression of COX-2 and inhibition of the ischaemia-induced
      dephosphorylation of Cx43. Therefore, M(3)-mAChRs represent a promising target
      for rendering cardiomyocytes tolerant to ischaemic injury.

PMID- 20128817
TI  - Effects of T-type calcium channel blockers and thalidomide on contractions of rat
      vas deferens.
AB  - BACKGROUND AND PURPOSE: In rat vas deferens, nerve mediated-contractions to a
      single electrical stimulus consist of an early purinergic and a later adrenergic
      component with differing sensitivities to L-type calcium channel blockers. We
      have investigated the effects of the T-type calcium channel blockers mibefradil
      and (1S, 2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro
      1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl cyclopropanecarboxylic
      dihydrochloride (NNC 55-0396) against contractions in rat vas deferens. In
      addition, the actions of thalidomide were examined. EXPERIMENTAL APPROACH:
      Prostatic and epididymal portions of rat vas deferens were stimulated with a
      single electrical stimulus every 5 min, and mouse whole vas deferens was
      stimulated with 40 pulses at 10 Hz every 5 min. KEY RESULTS: Both mibefradil and
      NNC 55-0396 (100 microM) produced inhibition of contractions of epididymal
      portions (42 +/- 13%, n= 7, and 43 +/- 4%, n= 15, of control respectively).
      However, both agents produced small inhibitions of responses in prostatic
      portions, presumably by L-type calcium channel block. Thalidomide (100 microM)
      inhibited contractions in epididymal (55 +/- 4% of control, n= 17) but not in
      prostatic portions of rat vas deferens. Thalidomide (10-100 microM) also
      inhibited contractions in mouse vas deferens. CONCLUSIONS AND IMPLICATIONS: The T
      type calcium channel blockers mibefradil and NNC 55-0396 block particularly the
      adrenoceptor-mediated, nifedipine-resistant response to nerve stimulation in rat
      vas deferens, and this may suggest that this component involves T-type calcium
      channels. In addition, thalidomide has actions that resemble those of the T-type
      calcium channel blockers, in that it blocks nifedipine-resistant contractions in
      epididymal portions.

PMID- 20128818
TI  - Serial analysis of gene expression of esophageal squamous cell carcinoma:
      ADAMTS16 is upregulated in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies
      worldwide. To identify potential diagnostic markers for ESCC and therapeutic
      targets for ESCC, we used Serial Analysis of Gene Expression (SAGE) on one ESCC
      sample. We obtained a total of 14,430 tags, including 5765 that were unique. By
      comparing SAGE tags from the ESCC sample with those from normal human squamous
      esophagus, we found several genes that were differentially expressed between ESCC
      and normal squamous esophagus. Among these, we focused on the ADAM
      metallopeptidase with thrombospondin type 1 motif, 16 (ADAMTS16) gene because
      quantitative RT-PCR analysis showed a high level of ADAMTS16 expression in eight
      out of 20 ESCC samples (40%), but not in 15 kinds of normal tissues. Western blot
      analysis also showed upregulation of ADAMTS16 protein in ESCC tissues.
      Furthermore, ADAMTS16 protein was detected in culture media from the TE5
      esophageal cancer cell line. Knockdown of ADAMTS16 in TE5 cells inhibited both
      cell growth and invasion ability. Our present SAGE data provide a list of genes
      potentially associated with ESCC. ADAMTS16 could be a novel diagnostic and
      therapeutic target for ESCC.

PMID- 20128819
TI  - Immunological evaluation of personalized peptide vaccination monotherapy in
      patients with castration-resistant prostate cancer.
AB  - We previously reported that personalized peptide vaccine (PPV) therapy in
      combination with leutenizing hormone-releasing hormone (LH-RH) analog and
      estramustine phosphate in certain cases is safe and capable of inducing both
      immune responses and clinical responses for metastatic castration-resistant
      prostate cancer (CRPC) patients. In the present study, PPV monotherapy was given
      to CRPC patients. Twenty-three patients with metastatic CRPC were treated with
      PPV without any additional treatment modalities, including LH-RH analogs. Samples
      were analyzed for peptide-specific cytotoxic T-lymphocyte (CTL) precursor
      analysis and peptide-reactive IgG. Toxicity and immunological and clinical
      responses were assessed on a three-monthly basis. Seventeen patients were
      available for immunological and clinical evaluation. The vaccines were well
      tolerated, with grade 3 erythema at injection sites in only one patient.
      Augmentation of CTL or IgG responses to at least one of the peptides was observed
      in six of 17 (35%) and 15 of 17 (88%) patients tested, respectively. Among 57
      peptides used, 9 and 36 peptides induced CTL and IgG responses, respectively.
      Delayed-type hypersensitivity reaction was observed in eight of 17 patients. More
      than 30% prostate-specific antigen (PSA) decline was observed in four of 17
      patients. Of these, one patient achieved a complete PSA response and another
      patient showed a partial PSA response with profound shrinking of lymph node
      metastases and prostate. The overall median survival time was 24 months (range, 5
      37 months). These results suggest that PPV monotherapy appears to be safe and
      capable of inducing peptide-specific immune responses and clinical responses in
      CRPC patients. This trial was registered with University Hospital Medical
      Information Network (UMIN) number R000003339.

PMID- 20128820
TI  - The role of oxysterol binding protein-related protein 5 in pancreatic cancer.
AB  - The expression of oxysterol binding protein-related protein (ORP) 5 is related to
      invasion and a poor prognosis in pancreatic cancer patients. ORP5 induced the
      expression of sterol response element binding protein (SREBP) 2 and activated the
      downstream gene of sterol response element. ChIP using SREBP2 antibody revealed
      that histone deacetylase 5 (HDAC5) was one of the downstream genes of SREBP2. The
      effect of HMG-CoA reductase inhibitors (statins) were analyzed according to the
      expression level of ORP5. The invasion rate and growth was suppressed in cells
      that strongly expressed ORP5 in a time- and dose-dependent manner, but had less
      effect in cells weakly expressing ORP5, suggesting that when the potential of
      invasion and growth relies on the cholesterol synthesis pathway, it becomes
      sensitive to HMG-CoA reductase inhibitor. Furthermore, HDAC inhibitor,
      tricostatin A, induced the expression of phosphatase and tensin homolog as well
      when ORP5 was suppressed or the cells were treated with statin. Treatment with
      both statin and tricostatin A showed a synergistic antitumor effect in cells that
      highly expressed ORP5. Therefore, in some pancreatic cancers, continuous ORP5
      expression enhances the cholesterol synthesis pathway and this signal
      transduction regulates phosphatase and tensin homolog through HDAC5 expression.
      This is the first report to detail how the signal transduction of cholesterol
      synthesis is related to cancer invasion and why statins can suppress invasion and
      growth.

PMID- 20128821
TI  - Differential expression of estrogen-related receptors beta and gamma (ERRbeta and
      ERRgamma) and their clinical significance in human prostate cancer.
AB  - Estrogen-related receptor (ERR) is a nuclear receptor that modulates the estrogen
      signaling pathway. Here, we investigated the expression of both ERRbeta and
      ERRgamma in human prostate tissues. Using original rabbit polyclonal anti-ERRbeta
      and anti-ERRgamma antibodies, the expression of ERRbeta and ERRgamma was
      evaluated by immunohistochemical analysis of cancerous lesions (n = 107) and
      benign foci (n = 92), obtained by radical prostatectomy. Stained slides were
      evaluated for the proportion of immunoreactive cells and their staining
      intensity. Total immunoreactivity scores (IR scores; range, 0-8) were calculated
      as the sum of the proportion and intensity scores. The relationship between the
      clinicopathological characteristics of the patients and the expression of the
      three ERRs (ERRalpha, ERR beta, and ERR gamma) was evaluated. IR scores for
      ERRbeta and ERRgamma were significantly lower in cancerous lesions than that in
      benign foci (P < 0.0001, for both). Clinicopathological analyses revealed that
      the patients with low ERRgamma IR scores (<or=4) tended to show poor cancer
      specific survival (P = 0.07). Then, we used data from our previous study
      (Fujimura T., Int J Cancer, 2007; 120: 2325-30). Patients with a high IR score
      for ERRalpha and a low score for ERRgamma showed significantly poorer cancer
      specific survival than those with a low IR score for ERRalpha and a high score
      for ERRgamma (P = 0.0003). We demonstrated the differential expression of ERRbeta
      and ERRgamma in prostate tissue. The combined evaluation of the expression of
      ERRalpha and ERRgamma could be a significant prognostic factor for prostate
      cancer.

PMID- 20128822
TI  - Initiation of malignancy by duodenal contents reflux and the role of ezrin in
      developing esophageal squamous cell carcinoma.
AB  - Gastroesophageal reflux has recently been implicated as a causative factor in
      upper aerodigestive tract carcinogenesis. Esophageal squamous cell carcinomas
      (ESCCs) have developed in duodenal-content reflux animals without any known
      carcinogen present. We established a cell line, designated ESCC-DR, from a
      thoracic metastatic tumor in a reflux animal. To gain insight into the genomic
      alterations associated with duodenal content reflux-induced carcinogenesis, we
      first performed comparative genomic hybridization using an Agilent rat 244K array
      in ESCC-DR and identified many chromosomal gains and losses. Of the many genes
      identified, we detected an interesting ezrin amplicon that has been recently
      reported in human ESCC. Ezrin, which cross-links the cytoskeleton and plasma
      membrane, is involved in the growth and metastatic potential of cancer cells.
      Overexpression of ezrin protein in ESCC-DR was confirmed by Western blotting. We
      also compared ezrin protein expression levels and patterns in hyperplastic,
      dysplastic, ESCC, and metastatic sites developed in two distinct reflux models
      using immunohistochemistry. Immunohistochemical staining of ezrin revealed
      overexpression in the nucleus, and the cytoplasm as well as plasma membrane of
      ESCC cells. Phosphorylated ERM (ezrin, radixin, moesin) was expressed at the
      leading edge, or invasive front, of larger metastatic sites. Taken together,
      duodenal reflux has a great potential for initiating malignancy, and thus likely
      plays a role in development of ESCC. Ezrin probably influences the growth and
      invasiveness of ESCC cells, and phosphorylation is only required in metastatic
      behavior of tumor cells at the leading edge and invasive front.

PMID- 20128823
TI  - Add-on montelukast to inhaled corticosteroids protects against excessive airway
      narrowing.
AB  - RATIONALE: Excessive airway narrowing in response to broncho-active stimuli is a
      predictor for severe exacerbations in asthma. Leukotriene receptor antagonists
      (LTRAs) have complementary properties to inhaled corticosteroids (ICS) on asthma
      control. OBJECTIVES: The LTRA montelukast may provide an additional protection
      against excessive airway narrowing. We tested the add-on effects of montelukast
      on the maximal response plateau and PD(20) to inhaled methacholine in asthmatics
      on a stable dose of ICS. METHODS: Thirty-one patients with allergic asthma
      [14M/17F, 19-50 years, forced expiratory volume in 1 s (FEV(1)) >70% pred.,
      PD(20) <3.9 micromol methacholine], with a twice documented response plateau to
      methacholine, were randomized in a double-blind (montelukast 10 mg or matching
      placebo once daily), 12-week parallel study. Bronchoprovocation tests with
      methacholine (0.03-256 micromol or > or =40% decline in FEV(1)) were repeated
      every 4 weeks and after wash-out. The main study objectives were changes from
      baseline in maximal FEV(1) decline at the response plateau (i.e. >2 post-dose
      FEV(1) values within 5%) and PD(20) to methacholine after 12 weeks' treatment.
      RESULTS: Neither treatment affected baseline FEV(1) (P=0.62). Compared with
      placebo, montelukast significantly decreased the maximal response plateau to
      methacholine (mean difference 9.4%; 95% confidence interval 3.9-15.7; P<0.005),
      improved the FEV(1) decline (mean change in FEV(1) decline was 2.1% [montelukast]
      and -0.8% [placebo], respectively, P<0.05), and increased PD(20) methacholine
      (mean change in PD(20) of 5.3 [montelukast] and 1.4 [placebo] doubling doses,
      respectively, P<0.001). CONCLUSION: Add-on montelukast to ICS has disease
      modifying effects in adults with persistent asthma, and hence reduces the risk of
      excessive airway narrowing (NCT 00913328).

PMID- 20128824
TI  - Two missense mutations in SLC26A4 gene: a molecular and functional study.
AB  - Mutations in the SLC26A4 gene encoding pendrin, an anion transporter, are
      responsible for non-syndromic hearing loss (HL) (DFNB4) and Pendred syndrome
      (PS). PS is a genetic disorder that causes early HL and affects the thyroid
      gland. Here, we report eight Tunisian families affected with profound HL.
      Clinical investigations revealed goiter in few patients. Genotyping using
      microsatellite makers showed linkage to SLC26A4, and missense mutations p.L445W
      and p.M147T were identified by sequencing and polymerase chain reaction
      restriction fragment length polymorphism. The p.L445W mutation segregated in
      seven families and haplotype analysis suggested its founder effect. In order to
      understand the molecular pathogenic mechanisms of p.L445W and p.M147T mutations,
      SLC26A4 wild-type and mutant cDNA constructs were transiently expressed in COS7
      cells and several human cell lines including Thyroid 8305C cells. Reverse
      transcription-PCR, western blot and immunofluorescence demonstrated that these
      two mutations abolished complex glycosylation of pendrin and prevented its
      targeting to the plasma membrane.

PMID- 20128826
TI  - Evaluation by quantitative magnetic resonance imaging of trabecular bone quality
      in mandible and cervical vertebrae.
AB  - OBJECTIVE: The purpose of this study was to make a comparison between mandibular
      and cervical vertebral bone quality (BQ) using quantitative magnetic resonance
      imaging (MRI). METHODS: The cervical MRI images included in this study belonged
      to 36 patients (23 women, 13 men; mean age 54 years) who had various clinical
      symptoms (e.g., headache, vertigo, imbalance). The mandible and cervical
      vertebrae BQ measurements were performed by the same investigator on these
      sections. Mandibular and cervical vertebral T2(*) axial cross sections were
      performed following receipt of consent from each patient. T2(*) relaxation time
      values were determined in the trabecular area. RESULTS: The relationship between
      cervical vertebral and mandibular BQ was revealed by regression and correlation
      analysis. The correlation coefficient was r=0.04, r(2)=0.002, and P=0.818, which
      is not statistically significant. The relation between age and mandible BQ was
      very weak (r=0.001, r(2)=0.000001, and P=0.995), and the relation between age and
      cervical vertebrae BQ was correlated (r=-0.585, r(2)=0.342, and P<0.001).
      CONCLUSIONS: There is a low correlation between the BQ measurements of cervical
      vertebrae and the mandible. Precise mandibular BQ measurement does not provide
      information that correlates with BQ in the other sites of the skeleton. Although
      an age-dependent decrease occurs in vertebral BQ, no significant alteration
      occurs in mandibular BQ.

PMID- 20128825
TI  - Modulation of immune responses through direct activation of Toll-like receptors
      to T cells.
AB  - Toll-like receptors (TLRs), which are a family of pattern recognition receptors
      (PRRs), are involved critically in the generation and regulation of innate
      immunity as well as initiation of subsequent adaptive immune responses. However,
      recent research results showed that different subsets of T cells express certain
      types of TLRs during development and activation stages. Importantly, TLRs
      participate in the direct regulation of adaptive immune response, possibly as co
      stimulatory molecules. In this review we summarize recent studies about the novel
      regulation of TLRs on the homeostasis and immunity of different T cell subtypes
      including CD4+CD25+T regulatory cells (Treg) and interleukin (IL)-17-producing
      CD4+T cells (T helper type 17). The direct involvement of TLRs in T cell-mediated
      immunity prompted us to reconsider the role of TLRs in the occurrence of
      autoimmune diseases, infectious diseases and graft rejection. The important
      effects of TLRs in T cell-intrinsic components also prompt us to explore novel
      vaccine adjuvants for modifying desired immune responses in an efficient way.

PMID- 20128827
TI  - A comparison of implant stability quotients measured using magnetic resonance
      frequency analysis from two directions: a prospective clinical study during the
      initial healing period.
AB  - OBJECTIVES: Given that the orientation of the transducer (mesiodistal or
      buccolingual) affects the data obtained from a piezoelectric resonance frequency
      analysis (RFA), this study evaluated whether it is necessary to use measurements
      taken in two different directions (mesiodistal and buccolingual) when using
      magnetic RFA to assess changes in the stiffness of dental implants. MATERIALS AND
      METHODS: A prospective clinical trial was completed, in a total of 53 patients,
      on 71 non-submerged dental implants that were inserted to replace the unilateral
      loss of mandibular molars. All of the implants were of the same diameter (4.1
      mm), length (10 mm), and collar height (2.8 mm). The implant stability quotient
      (ISQ) was measured during the surgical procedure, and at 4 and 10 weeks after
      surgery. Measurements were taken twice in each direction: in the buccolingual
      direction from the buccal side and in the mesiodistal direction from the mesial
      side. The average of two measurements in each direction was regarded as the
      representative ISQ of that direction. The higher and lower values of the two ISQs
      (buccolingual and mesiodistal) were also classified separately. In addition, the
      variation in ISQ was quantified by subtracting the lower value from the higher
      value, and the implants were classified into two groups according to this
      variation: one with ISQ variation of 3 or more and the other with a variation of
      <3. RESULTS: There were no differences between the two ISQs when measured from
      different directions, but there were significant differences between the higher
      and lower values of the ISQs at each measurement point. A significant difference
      was also observed between the two ISQ variation groups in the pattern of change
      of the lower value for the period from immediately after surgery to 10 weeks
      after surgery. CONCLUSION: Acquisition of two directional measurements and
      classification of the higher and lower values of the two directional ISQs may
      allow clinicians to detect patterns of change in ISQ that would not be identified
      if only one directional measurement were made.

PMID- 20128828
TI  - A comparison of two implant techniques on patient-based outcome measures: a
      report of flapless vs. conventional flapped implant placement.
AB  - BACKGROUND: Flapless implant surgery is considered to offer advantages over the
      traditional flap access approach. There may be minimized bleeding, decreased
      surgical times and minimal patient discomfort. Controlled studies comparing
      patient outcome variables to support these assumptions, however, are lacking.
      AIM: The objective of this clinical study was to compare patient outcome
      variables using flapless and flapped implant surgical techniques. PATIENTS AND
      METHODS: From January 2008 to October 2008, 16 consecutive patients with
      edentulous maxillas were included in the study. Patients were randomly allocated
      to either implant placement with a flapless procedure (eight patients, mean age
      54.6 + or - 2.9 years) or surgery with a conventional flap procedure (eight
      patients, mean age 58.7 + or - 7.2 years). All implants were placed using a Nobel
      guide CT-guided surgical template. Outcome measures were the Dutch version of the
      Impact of Event Scale-Revised (IES-R), dental anxiety using the s-DAI and oral
      health-related quality of life (OHIP-14). RESULTS: Ninety-six implants were
      successfully placed. All implants were placed as two-phase implants and the after
      implant placement dentures were adapted. No differences could be shown between
      conditions on dental anxiety (s-DAI), emotional impact (IES-R), anxiety,
      procedure duration or technical difficulty, although the flapless group did score
      consistently higher. The flap procedure group reported less impact on quality of
      life and included more patients who reported feeling no pain at all during
      placement. CONCLUSIONS: Differences found in the patient outcome variables do
      suggest that patients in the flapless implant group had to endure more than
      patients in the flap group.

PMID- 20128829
TI  - Prospective study with a 2-year follow-up on immediate implant loading in the
      edentulous mandible with a definitive restoration using intra-oral welding.
AB  - OBJECTIVES: The aim of this prospective study was to evaluate the concept of
      intra-oral welding as a suitable technique for the fabrication of a restoration
      for edentulous mandibles on the same day as surgery using tapered connection
      implants. MATERIAL AND METHODS: Each of 20 patients had an edentulous mandible
      and received four inter-foraminal, tapered connection implants. All implants were
      immediately loaded with a fixed restoration supported by an intra-orally welded
      titanium framework. Final abutments were connected to the implants and then a
      titanium bar was welded to them using an intra-oral welding unit. This framework
      was used as a support for the final restoration, which was fitted on the same day
      as implant placement. Mean marginal bone loss and radiographically detectable
      alteration of the welded framework were assessed using periapical radiographs
      immediately after surgery, and at 6-, 12- and 24-month follow-up examinations.
      RESULTS: Seven males and 13 females, with an average age of 56.5 years (SD=15.1;
      n=20), were consecutively treated with 80 immediately loaded implants. No
      fracture or radiographically detectable alteration of the welded frameworks was
      evident. All implants osseointegrated and a 100% implant survival rate was
      achieved at the 24-month follow-up. The accumulated mean marginal bone growth was
      0.21 mm (SD 0.25, n=80). The average pocket probing depth was 1.38 mm (SD 0.41).
      CONCLUSIONS: The intra-oral welding technique applied to the delivery of a final
      restoration of the edentulous mandible over immediately restored tapered
      connection implants seems to have no adverse effect on marginal bone loss and
      implant survival.

PMID- 20128830
TI  - Enhanced osteoblast response to hydrophilic strontium and/or phosphate ions
      incorporated titanium oxide surfaces.
AB  - OBJECTIVE: This study investigated the surface characteristics and in vitro
      biocompatibility of titanium (Ti) surfaces incorporated with strontium ions (Sr)
      and/or phosphate ions (P) produced by hydrothermal treatment for future
      applications as endosseous implant surfaces. MATERIAL AND METHODS: Sr and/or P
      incorporated Ti oxide surfaces were produced by hydrothermal treatment. The
      surface characteristics were evaluated by scanning electron microscopy, thin-film
      X-ray diffractometry, X-ray photoelectron spectroscopy, contact angle and surface
      energy measurements, inductively coupled plasma atomic emission spectroscopy, and
      profilometry. MC3T3-E1 pre-osteoblast cell attachment, morphology of spread
      cells, viability, and quantitative analysis of osteoblastic gene expression on
      grit-blasted microrough (RBM), P-incorporated (P), and P- and Sr-incorporated
      (SrP) Ti surfaces were evaluated. RESULTS: Microstructured P and SrP surfaces
      showed significantly higher wettability and surface energy compared with RBM
      surfaces (P<0.01). After immersion in Hank's balanced salt solution, considerable
      apatite deposition was observed on the P and SrP surfaces. Sr incorporation
      significantly increased cellular attachment and viability compared with other
      surfaces (P<0.05). Real-time polymerase chain reaction analysis showed markedly
      higher mRNA expressions of the osteoblast transcription factor gene (Runx2) and
      the osteoblast phenotype genes (alkaline phosphatase, osteopontin, bone
      sialoprotein, and osteocalcin) in cells grown on the P and SrP surfaces compared
      with those on the RBM surface. CONCLUSIONS: These results demonstrate that Sr-
      and P-incorporated Ti oxide surfaces may improve implant bone healing by
      enhancing attachment, viability, and differentiation of osteoblastic cells.

PMID- 20128831
TI  - Comparison of two full-mouth approaches in the treatment of peri-implant
      mucositis: a pilot study.
AB  - OBJECTIVES: The aim of the present study was to test the hypothesis that an
      additional full-mouth disinfection results in a greater clinical and
      microbiological improvement compared with sole mechanical debridement within one
      session in patients with peri-implant mucositis and treated chronic
      periodontitis. MATERIAL AND METHODS: The study included 13 partially edentulous
      patients (mean age 51.5 years) with treated chronic periodontitis and 36 dental
      implants with mucositis (bleeding on probing and/or a gingival index > or =1 at
      least at one site at baseline, absence of peri-implant bone loss during the last
      2 years before baseline). After randomized assignment to a test and a control
      group, patients received a one-stage full-mouth scaling with or without
      chlorhexidine. Clinical and microbiological examination was performed at
      baseline, after 1, 2, 4 and 8 months. Additional microbial samples were taken 24
      h after treatment. Microbiological analysis was performed by real-time polymerase
      chain reaction. RESULTS: Both treatment modalities resulted in significant
      reductions of probing depth at implant sites after 8 months, with no significant
      group differences. The bacteria at implants and teeth could be reduced in every
      group 24 h after treatment; however, this reduction was not significant after 8
      months. CONCLUSIONS: Both treatment modalities led to an improvement of the
      clinical parameters and a temporary reduction of the microflora at implants with
      mucositis, but without significant inter-group differences after 8 months.

PMID- 20128832
TI  - Influence of interimplant distances and placement depth on peri-implant bone
      remodeling of adjacent and immediately loaded Morse cone connection implants: a
      histomorphometric study in dogs.
AB  - OBJECTIVES: The aim of this study was to histomorphometrically evaluate the
      influence of interimplant distances (ID) and implant placement depth on bone
      remodeling around contiguous Morse cone connection implants with 'platform
      shifting' in a dog model. MATERIAL AND METHODS: Bilateral mandibular premolars of
      six dogs were extracted, and after 12 weeks, each dog received 8 implants, four
      placed 1.5 mm subcrestally (SCL) on one side of the mandible and four placed
      equicrestally (ECL) on the other side, alternating the ID of 2 and 3 mm. The
      experimental groups were SCL with IDs of 2 mm (2 SCL) and 3 mm (3 SCL) and ECL
      with IDs of 2 mm (2 ECL) and 3 mm (3 ECL). Metallic crowns were immediately
      installed. After 8 weeks, the animals were euthanized and histomorphometric
      analyses were performed to compare bone remodeling in the groups. RESULTS: The
      SCL groups' indices of crestal bone resorption were significantly lower than
      those of ECL groups. In addition, the vertical bone resorption around the
      implants was also numerically inferior in the SCL groups, but without statistical
      significance. No differences were obtained between the different IDs. All the
      groups presented similar good levels of bone-to-implant contact and histological
      bone density. CONCLUSION: The subcrestal placement of contiguous Morse cone
      connection implants with 'platform shifting' was more efficient in preserving the
      interimplant crestal bone. The IDs of 2 and 3 mm did not affect the bone
      remodeling significantly under the present conditions.

PMID- 20128833
TI  - Colon cancer incidence, presentation, treatment and outcomes over 25 years.
AB  - AIM: The aim of this study was to evaluate changes in the incidence,
      presentation, treatment and outcome of colon cancer in a complete cohort of
      patients treated at a single institution over a 25-year period. METHOD: All 869
      patients at Levanger Hospital, Norway with colon cancer during 1980-2004 were
      included in the study. RESULTS: The incidence of colon cancer increased by 2.1%
      per year. During the later years, patients presented with less advanced stages,
      and fewer patients had emergency presentation with obstruction. The rate of
      operations performed by a colorectal specialist attending increased from 56 to
      98%. Postoperative mortality after resection with curative intent decreased from
      6.3 to 3.2%, and the presence of a colorectal specialist during the operation was
      an independent factor that reduced the risk of postoperative death. The local
      recurrence rate after curative surgery was 10.9% (19 of 174) in 1980-1989, 5.9%
      (14 of 239) in 1990-1999 and 0.6% (1 of 154) in 2000-2004 (P < 0.001). The 5-year
      relative survival after resection with curative intent was 71, 81 and 85% in the
      three periods 1980-1989, 1990-1999 and 2000-2004, respectively. CONCLUSION: The
      outcome of colon cancer improved from 1980 to 2004. Patients presented at earlier
      stages, and fewer had emergency presentation. The local recurrence and
      postoperative mortality rates were reduced, and relative survival improved.

PMID- 20128834
TI  - UK coloproctologists' current opinions on anastomotic technique and
      configuration.

PMID- 20128835
TI  - Training the trainees will improve uptake of laparoscopic colorectal surgery.

PMID- 20128836
TI  - Transanal endoscopic microsurgery repair of rectourethral fistula after high
      intensity focused ultrasound ablation of prostate cancer.

PMID- 20128837
TI  - Colorectal carcinoma in young adults: a retrospective study on Indian patients:
      2000-2008.
AB  - AIM: To highlight an increased incidence of colorectal cancer (CRC) amongst young
      Indian adults. METHOD: A retrospective study of 305 cases of CRC admitted to SSKM
      Hospital, Kolkata, India during 2000-2008 was carried out. RESULTS: The ratio
      (0.64) of under-40 to above-40 CRC patients reported in this study is comparable
      to those from premier Oncology Centers in India (~0.52) and is higher than those
      in the Indian National Cancer Registry (~0.20) and international average (0.07).
      Distinctive tumour characteristics in younger patients including left-sided
      lesion (69.7%), presentation at an advanced (III/IV) stage (60%), poor
      histological differentiation (50%) and predominance of mucin-secreting
      adenocarcinoma (80%) are similar to those reported in the international
      literature. Some features are suggestive of hereditary non polyposis colorectal
      cancer syndrome, which may be a possible reason for the high proportion of young
      CRC patients. CONCLUSION: A high index of suspicion for CRC among young Indian
      adults is necessary.

PMID- 20128838
TI  - Sacral transcutaneous electrical nerve stimulation in the treatment of idiopathic
      faecal incontinence.
AB  - AIM: The aim of this study was to investigate the potential use of S3
      transcutaneous electrical nerve stimulation (TENS) in the treatment of idiopathic
      faecal incontinence. METHOD: Seventeen patients were treated by S3 TENS 2 h a day
      for 3 months. The outcome was evaluated by faecal incontinence severity index
      (FISI), faecal incontinence quality of life scale (FIQOL), 7-day bowel diary,
      anorectal physiology, patients' self-reported impression of improvement, bowel
      control and satisfaction with treatment on a visual analogue scale. RESULTS:
      Seventeen patients (13 women) of mean age 67.2 years (52-80) were followed up for
      a mean of 19.7 months. The FISI improved in 69% after 3 months of TENS (P <
      0.01), and all components of FIQOL improved. The number of incontinent episodes
      per week fell for incontinence to gas and stool (solid and/or liquid). There was
      no significant difference in the maximum resting pressure and squeeze pressure,
      but the mean rectal volume of first sensation (12.1 ml, P = 0.027) and first urge
      (25.0 ml, P = 0.054) fell, and the maximum tolerable volume (16.0 ml, P = 0.679)
      rose. The satisfaction score was >= 6/10 in all patients. Fifteen (88%) scored >=
      6/10 for bowel control, and all patients scored >= 2 (scale: -5 to +5) for their
      impression of improvement. CONCLUSION: S3 transcutaneous electrical nerve
      stimulation seems to be a promising noninvasive method to treat faecal
      incontinence. However, further study is required.

PMID- 20128839
TI  - Influences on length of stay in an enhanced recovery programme after colonic
      surgery.
AB  - AIM: Enhanced recovery after surgery (ERAS) programmes have been shown to
      accelerate and enhance functional recovery after colonic surgery. We analysed
      prospectively collected data to investigate potentially modifiable factors that
      may influence the length of stay (LOS) in the ERAS setting at a single
      institution. METHOD: Between October 2005 and November 2008, prospective data
      were collected on consecutive patients who underwent elective colonic surgery
      without a stoma. Patients with rectal cancer, those unable to participate in
      preoperative ERAS components because of their inability to communicate
      effectively in English, those with cognitive impairment and those with an
      American Society of Anesthesiologists (ASA) grade of >= 4 were excluded.
      Statistical analyses were performed using the Mann-Whitney U-test and Cox
      regression modelling. RESULTS: A total of 100 (79 malignancies) patients
      underwent elective colon resection during the study period. There were 57 right
      sided, 41 left-sided and two total colectomies. The median age of the patients
      was 67.5 (range 31-92) years and the median day stay was 4 (range 3-46) days.
      Factors with significant correlations for reduced LOS were female gender, the
      surgeon, operative severity, high-dependency unit (HDU) admission and incision
      type favouring laparoscopic and transverse approaches. Age, operation site,
      indication for surgery and body mass index were not significant predictors of
      hospital stay. Gender, operative severity, HDU admission and surgeon did not have
      any independent correlation with LOS; in contrast to the ASA score and the type
      of incision, which did. CONCLUSION: Lower ASA score, transverse incision
      laparotomy and laparoscopy correlated independently with reduced postoperative
      LOS within the ERAS setting.

PMID- 20128840
TI  - Assessment of posterior compartment prolapse; a comparison of evacuation
      proctography and 3D transperineal ultrasound.

PMID- 20128841
TI  - A collaboration conducive to conduction: matching axonal density to
      oligodendroglial number (Commentary on Kawai et al.).

PMID- 20128842
TI  - Maintenance of the relative proportion of oligodendrocytes to axons even in the
      absence of BAX and BAK.
AB  - Highly purified oligodendroglial lineage cells from mice lacking functional bax
      and bak genes were resistant to apoptosis after in-vitro differentiation,
      indicating an essential role of the intrinsic apoptotic pathway in apoptosis of
      oligodendrocytes in the absence of neurons (axons) and other glial cells. These
      mice therefore provide a valuable tool with which to evaluate the significance of
      the intrinsic apoptotic pathway in regulating the population sizes of
      oligodendrocytes and oligodendroglial progenitor cells. Quantitative analysis of
      the optic nerves and the dorsal columns of the spinal cord revealed that the
      absolute numbers of mature oligodendrocytes immunolabeled for aspartoacylase and
      adult glial progenitor cells expressing NG2 chondroitin sulfate proteoglycan were
      increased in both white matter tracts of adult bax/bak-deficient mice and, to a
      lesser extent, bax-deficient mice, except that there was no increase in NG2
      positive progenitor cells in the dorsal columns of these strains of mutant mice.
      These increases in mature oligodendrocytes and progenitor cells in bax/bak
      deficient mice were unexpectedly proportional to increases in numbers of axons in
      these white matter tracts, thus retaining the oligodendroglial lineage to axon
      ratios of at most 1.3-fold of the physiological numbers. This is in contrast to
      the prominent expansion in numbers of neural precursor cells in the
      subventricular zones of these adult mutant mice. Our study indicates that
      homeostatic control of cell number is different for progenitors of the
      oligodendroglial and neuronal lineages. Furthermore, regulatory mechanism(s)
      operating in addition to apoptotic elimination through the intrinsic pathway,
      appear to prevent the overproduction of highly mitotic oligodendroglial
      progenitor cells.

PMID- 20128843
TI  - Activity-driven mobilization of post-synaptic proteins.
AB  - Synapses established during central nervous system development can be modified
      through synapse elimination and formation. These processes are, in part, activity
      dependent and require regulated trafficking of post-synaptic components. Here, we
      investigate the activity-driven remodeling of cultured rat hippocampal neurons at
      14 days in vitro, focusing on the post-synaptic proteins PSD-95, Shank,
      neuroligin (NL)1 and actin. Using live imaging and photoconductive stimulation,
      we found that high-frequency activity altered the trajectory, but not velocity,
      of PSD-95-GFP and Shank-YFP clusters, whereas it reduced the speed and increased
      the number of NL1 clusters. Actin-CFP reorganized into puncta following activity
      and approximately 50% of new puncta colocalized with NL1 clusters. Actin
      reorganization was enhanced by the overexpression of NL1 and decreased by the
      expression of an NL1 mutant, NL1-R473C. These results demonstrate activity
      dependent changes that may result in the formation of new post-synaptic sites and
      suggest that NL1 modulates actin reorganization. The results also suggest that a
      common mechanism underlies both the developmental and activity-dependent
      remodeling of excitatory synapses.

PMID- 20128844
TI  - Parvalbumin-containing neurons, perineuronal nets and experience-dependent
      plasticity in murine barrel cortex.
AB  - The ability to undergo experience-dependent plasticity in the neocortex is often
      limited to early development, but also to particular cortical loci and specific
      experience. In layers II-IV of the barrel cortex, plasticity evoked by removing
      all but one vibrissae (univibrissa rearing) does not have a time limit except for
      layer IV barrels, where it can only be induced during the first postnatal week.
      In contrast, deprivation of every second vibrissa (chessboard deprivation)
      removes time limits for plasticity. The mechanism permitting plasticity in
      response to chessboard deprivation and halting it in reply to univibrissa rearing
      is unknown. Condensation of chondroitin sulfate proteoglycans into perineuronal
      nets and an increase in intracortical inhibition mediated by parvalbumin
      containing interneurons are implicated in closing the critical period for ocular
      dominance plasticity. These factors could also be involved in setting up the
      critical period in barrels in a way that depends on a particular sensory
      experience. We therefore examined changes in density of parvalbumin-containing
      cells and perineuronal nets during development of mouse barrel cortex and after
      brief univibrissa and chessboard experience in adolescence. We observed a
      progressive increase in the density of the two markers across cortical layers
      between postnatal day 10 and 20, which was especially pronounced in the barrels.
      Univibrissa rearing, but not chessboard deprivation, increased the density of
      perineuronal nets and parvalbumin-containing cells in the deprived barrels, but
      only those that immediately neighbour the undeprived barrel. These data suggest
      the involvement of both tested factors in closing the critical period in barrels
      in an experience-dependent manner.

PMID- 20128846
TI  - Short-term synaptic plasticity at the main and vomeronasal olfactory receptor to
      mitral cell synapse in frog.
AB  - Synaptic responses resulting from stimulation of the main olfactory and
      vomeronasal (VN) nerves were measured in main and accessory olfactory bulb (AOB)
      of frog, Rana pipiens, to test the hypothesis that properties of these synapses
      would reflect the distinct differences in the time course of odour delivery to
      each of these olfactory structures. Paired-pulse depression dominated responses
      to repetitive stimulation of the main olfactory nerve for interstimulus intervals
      (ISI) up to several seconds. Inhibition of voltage-gated Ca(2+) channels by GABAb
      receptors contributes significantly to this inhibition of transmitter release,
      particularly for ISI > 0.5 s. In contrast, the monosynaptic connection between VN
      sensory neurons and mitral cells in the AOB showed enhancement with pairs or
      short trains of stimuli for ISI of 0.5 to > 10 s. A small inhibitory effect of
      GABAb receptors on presynaptic Ca(2+) influx and release was only evident when a
      large proportion of the VN axons were stimulated simultaneously but even with
      inhibition present an overall enhancement of release was observed. Increasing the
      number of conditioning stimuli from one to five increased residual [Ca(2+)] and
      enhancement but a direct correlation between residual [Ca(2+)] and either the
      magnitude or the time course of enhancement was not observed. Enhanced
      transmitter release from VN afferent terminals results in effective integration
      of sustained low-frequency activity, which may play a role in the detection of
      low-intensity odourant stimuli by the VN system.

PMID- 20128845
TI  - Engineering neuronal nicotinic acetylcholine receptors with functional
      sensitivity to alpha-bungarotoxin: a novel alpha3-knock-in mouse.
AB  - We report here the construction of a novel knock-in mouse expressing chimeric
      alpha3 nicotinic acetylcholine receptor (nAChR) subunits with pharmacological
      sensitivity to alpha-bungarotoxin (alphaBTX). Sensitivity was generated by
      substituting five amino acids in the loop C (beta9-beta10) region of the mouse
      alpha3 subunit with the corresponding residues from the alpha1 subunit of the
      muscle type receptor from Torpedo californica. To demonstrate the utility of the
      underlying concept, expressed alpha3[5] subunits were characterized in the
      superior cervical ganglia (SCG) of homozygous knock-in mice, where the synaptic
      architecture of postsynaptic alpha3-containing nAChR clusters could now, for the
      first time, be directly visualized and interrogated by live-staining with
      rhodamine-conjugated alphaBTX. Consistent with the postsynaptic localization of
      ganglionic nAChRs, the alphaBTX-labeled puncta colocalized with a marker for
      synaptic varicosities. Following in vivo deafferentation, these puncta persisted
      but with significant changes in intensity and distribution that varied with the
      length of the recovery period. Compound action potentials and excitatory
      postsynaptic potentials recorded from SCG of mice homozygous for alpha3[5] were
      abolished by 100 nmalphaBTX, even in an alpha7 null background, demonstrating
      that synaptic throughput in the SCG is completely dependent on the alpha3
      subunit. In addition, we observed that the genetic background of various inbred
      and outbred mouse lines greatly affects the functional expression of alpha3[5]
      nAChRs, suggesting a powerful new approach for exploring the molecular mechanisms
      underlying receptor assembly and trafficking. As alphaBTX-sensitive sequences can
      be readily introduced into other nicotinic receptor subunits normally insensitive
      to alphaBTX, the findings described here should be applicable to many other
      receptors.

PMID- 20128847
TI  - Extinction of cued fear memory involves a distinct form of depotentiation at
      cortical input synapses onto the lateral amygdala.
AB  - The amygdala is known to be a critical storage site of conditioned fear memory.
      Among the two major pathways to the lateral amygdala (LA), the cortical pathway
      is known to display a presynaptic long-term potentiation which is occluded with
      fear conditioning. Here we show that fear extinction results in a net depression
      of conditioning-induced potentiation at cortical input synapses onto the LA (C-LA
      synapses). Fear conditioning induced a significant potentiation of excitatory
      postsynaptic currents at C-LA synapses compared with naive and unpaired controls,
      whereas extinction apparently reversed this potentiation. Paired-pulse low
      frequency stimulation (pp-LFS) induced synaptic depression in the C-LA pathway of
      fear-conditioned rats, but not in naive or unpaired controls, indicating that the
      pp-LFS-induced depression is specific to associative learning-induced changes (pp
      LFS-induced depotentiation(ex vivo)). Importantly, extinction occluded pp-LFS
      induced depotentiation(ex vivo), suggesting that extinction shares some
      mechanisms with the depotentiation. pp-LFS-induced depotentiation(ex vivo)
      required NMDA receptor (NMDAR) activity, consistent with a previous finding that
      blockade of amygdala NMDARs impaired fear extinction. In addition, pp-LFS-induced
      depotentiation(ex vivo) required activity of group II metabotropic glutamate
      receptors (mGluRs), known to be present at presynaptic terminals, but not AMPAR
      internalization, consistent with a presynaptic mechanism for pp-LFS-induced
      depotentiation(ex vivo). This result is in contrast with another form of ex vivo
      depotentiation in the thalamic pathway that requires both group I mGluR activity
      and AMPAR internalization. We thus suggest that extinction of conditioned fear
      involves a distinct form of depotentiation at C-LA synapses, which depends upon
      both NMDARs and group II mGluRs.

PMID- 20128848
TI  - Long-term synaptic plasticity is impaired in rats with lesions of the
      ventrolateral preoptic nucleus.
AB  - Impairment of memory functions has been frequently reported in models of sleep
      deprivation. Similarly, hippocampal long-term synaptic plasticity has been shown
      to be sensitive to sleep loss caused by acute sleep restriction. However, such
      approaches are limited by the stressful nature of sleep deprivation, and because
      it is difficult to study long-term sleep restriction in animals. Here, we report
      the effects of chronic sleep loss on hippocampal long-term potentiation (LTP) in
      a rodent model of chronic partial sleep deprivation. We studied LTP of the
      Schaffer collateral-CA1 synapses in hippocampal slices prepared from rats with
      lesions of the ventrolateral preoptic nucleus (VLPO), which suffered reductions
      in total sleep time for several weeks after lesions. In slices prepared from VLPO
      lesioned rats, LTP was impaired proportionally to the amount of sleep loss, and
      the decline in LTP followed a single exponential function over the amount of
      accumulated sleep debt. As compared with sham-lesioned controls, hippocampal
      slices from VLPO-lesioned rats showed a greater response to adenosine antagonists
      and greater paired-pulse facilitation (PPF). However, exogenous adenosine
      depressed evoked synaptic transmission and increased PPF in VLPO-lesioned and
      sham-lesioned rats by equal amounts, suggesting that the greater endogenous
      adenosine inhibitory tone in the VLPO-lesioned rats is associated with greater
      ligand accumulation rather than a change in adenosine receptor sensitivity or
      adenosine-mediated neurotransmitter release probability. LTP in VLPO-lesioned
      animals was partially restored by adenosine antagonists, suggesting that
      adenosine accumulation in VLPO-lesioned animals could account for some of the
      observed synaptic plasticity deficits.

PMID- 20128849
TI  - In vivo voltammetric monitoring of norepinephrine release in the rat ventral bed
      nucleus of the stria terminalis and anteroventral thalamic nucleus.
AB  - The role and contribution of the dense noradrenergic innervation in the ventral
      bed nucleus of the stria terminalis (vBNST) and anteroventral thalamic nucleus
      (AV) to biological function and animal behaviors is poorly understood due to the
      small size of these nuclei. The aim of this study was to compare norepinephrine
      release and uptake in the vBNST with that in the AV of anesthetized rats.
      Measurements were made in vivo with fast-scan cyclic voltammetry following
      electrical stimulation of noradrenergic projection pathways, either the dorsal
      noradrenergic bundle (DNB) or the ventral noradrenergic bundle (VNB). The
      substance detected was identified as norepinephrine based upon voltammetric,
      anatomical, neurochemical and pharmacological evidence. Fast-scan cyclic
      voltammetry enables the selective monitoring of local norepinephrine overflow in
      the vBNST evoked by the stimulation of either the DNB or the VNB while
      norepinephrine in the AV was only evoked by DNB stimulation. The alpha2
      adrenoceptor antagonist yohimbine and the norepinephrine uptake inhibitor
      desipramine increased norepinephrine overflow and slowed its disappearance in
      both regions. However, control of extracellular norepinephrine by both
      autoreceptors and uptake was greater in the AV. The greater control exerted by
      autoreceptors and uptake in the AV resulted in reduced extracellular
      concentration compared with the v BNST when large numbers of stimulation pulses
      were employed. The differences in noradrenergic transmission observed in the
      terminal fields of the v BNST and the AV may differentially regulate activity in
      these two regions that both contain high densities of norepinephrine terminals.

PMID- 20128850
TI  - Embryonic striatal grafts restore bi-directional synaptic plasticity in a rodent
      model of Huntington's disease.
AB  - Embryonic striatal grafts integrate with the host striatal circuitry, forming
      anatomically appropriate connections capable of influencing host behaviour. In
      addition, striatal grafts can influence host behaviour via a variety of non
      specific, trophic and pharmacological mechanisms; however, direct evidence that
      recovery is dependent on circuit reconstruction is lacking. Recent studies
      suggest that striatal grafts alleviate simple motor deficits, and also that
      learning of complex motor skills and habits can also be restored. However,
      although the data suggest that such 're-learning' requires integration of the
      graft into the host striatal circuitry, little evidence exists to demonstrate
      that such integration includes functional synaptic connections. Here we
      demonstrate that embryonic striatal grafts form functional connections with the
      host striatal circuitry, capable of restoring stable synaptic transmission,
      within an excitotoxic lesion model of Huntington's disease. Furthermore, such
      'functional integration' of the striatal graft enables the expression of host
      graft bi-directional synaptic plasticity, similar to the normal cortico-striatal
      circuit. These results indicate that striatal grafts express synaptic correlates
      of learning, and thereby provide direct evidence of functional neuronal circuit
      repair, an essential component of 'functional integration'.

PMID- 20128851
TI  - Dopamine-oxytocin interactions in penile erection.
AB  - Dopamine and oxytocin have established roles in the central regulation of penile
      erection in rats; however, the neural circuitries involved in a specific erectile
      context and the interaction between dopamine and oxytocin mechanisms remain to be
      elucidated. The medial preoptic area (MPOA), supraoptic nucleus (SON) and
      paraventricular nucleus (PVN) of the hypothalamus may serve as candidate sites
      because they contain oxytocin cells, receive dopaminergic inputs and have been
      implicated in mediating masculine sexual behavior. Double immunofluorescence
      revealed that substantial numbers of oxytocin cells in the MPOA, SON and PVN
      possess dopamine D(2), D(3) and D(4) receptors. In anaesthetized rats, using
      intracavernous pressure as a physiological indicator of erection, blockade of
      lumbosacral oxytocin receptors (UK, 427843) reduced erectile responses to a
      nonselective dopamine agonist (apomorphine), suggesting that dopamine recruits a
      paraventriculospinal oxytocin pathway. In conscious males in the absence of a
      female, penile erection elicited by a D(2)/D(3) (Quinelorane) but not D(4)
      (PD168077) agonist was associated with activation of medial parvocellular PVN
      oxytocin cells. In another experiment where males were given full access to a
      receptive female, a D(4) (L-745870) but not D(2) or D(3) antagonist (L-741626;
      nafadotride) inhibited penile erection (intromission), and this was correlated
      with SON magnocellular oxytocin neuron activation. Together, the data suggest
      dopamine's effects on hypothalamic oxytocin cells during penile erection are
      context-specific. Dopamine may act via different parvocellular and magnocellular
      oxytocin subpopulations to elicit erectile responses, depending upon whether
      intromission is performed. This study demonstrates the potential existence of
      interaction between central dopamine and oxytocin pathways during penile
      erection, with the SON and PVN serving as integrative sites.

PMID- 20128852
TI  - Neural correlates of conflict resolution between automatic and volitional actions
      by basal ganglia.
AB  - A dominant basal ganglia (BG) model consists of two functionally opposite
      pathways: one facilitates motor output and the other suppresses it. Although this
      idea was originally proposed to account for motor deficits, it has been extended
      recently also to explain cognitive deficits. Here, we employed the antisaccade
      paradigm (look away from a stimulus) to address the role of the caudate nucleus,
      the main BG input stage where the two pathways diverge, in conflict resolution.
      Using single neuron recordings in awake monkeys, we identified the following
      three groups of neurons. The first group of neurons showed activity consistent
      with sensory-driven (automatic) saccades toward a contralateral visual stimulus.
      The second group of neurons showed activity consistent with internally driven
      (volitional) saccades toward the contralateral side regardless of stimulus
      locations. The third group of neurons showed similar firing characteristics with
      the second group of neurons, except that their preferred saccade direction was
      ipsilateral. The activity of the three groups of neurons was correlated with
      behavioral outcome. Based on these findings, we suggest the following hypothesis:
      the first and second groups of neurons encoding automatic and volitional
      saccades, respectively, might give rise to the facilitation (direct) pathway and
      promote saccades toward the opposite directions, which creates a response
      conflict. This conflict could be resolved by the third group of caudate neurons,
      which might give rise to the suppression (indirect) pathway and attenuate
      inappropriate saccade commands toward the stimulus.

PMID- 20128853
TI  - The role of the hippocampus in mnemonic integration and retrieval: complementary
      evidence from lesion and inactivation studies.
AB  - Two forms of account have been proposed for how animals form integrated memories
      for patterns of stimulation: the elemental account holds that the elements that
      make up the pattern become directly linked to one another, whereas the configural
      account holds that these elements become bound together through their capacity to
      activate a separate, shared configural memory. The hippocampus and perirhinal
      cortex have been linked to both elemental and configural processes. Here, we
      assessed the role of the rat hippocampus and perirhinal cortex in these distinct
      ways of processing patterns of sensory stimulation involving auditory, visual
      context and temporal information. Using selective lesions and inactivation
      techniques we identified a specific role for the hippocampus in the retrieval of
      configural memories but not of those that could be encoded elementally; we also
      identified a role for the rat perirhinal cortex in visual contextual learning.
      These results, using a novel combination of behavioural assays, provide clear
      support for the view that patterns of stimulation can be encoded either
      elementally or configurally, and that disruption of hippocampal function leaves
      rats reliant on elemental processes.

PMID- 20128854
TI  - Role of polysialylated neural cell adhesion molecule in rapid eye movement sleep
      regulation in rats.
AB  - Recent evidence suggests that synaptic plasticity occurs during homeostatic
      processes, including sleep-wakefulness regulation, although the underlying
      mechanisms are not well understood. Polysialylated neural cell adhesion molecule
      (PSA NCAM) is a transmembrane protein that has been implicated in various forms
      of plasticity. To investigate whether PSA NCAM is involved in the neuronal
      plasticity associated with spontaneous sleep-wakefulness regulation and sleep
      homeostasis, four studies were conducted using rats. First, we showed that PSA
      NCAM immunoreactivity is present in close proximity to key neurons in several
      nuclei of the sleep-wakefulness system, including the tuberomammillary
      hypothalamic nucleus, dorsal raphe nucleus, and locus coeruleus. Second, using
      western blot analysis and densitometric image analysis of immunoreactivity, we
      found that 6 h of sleep deprivation changed neither the levels nor the general
      location of PSA NCAM in the sleep-wakefulness system. Finally, we injected
      endoneuraminidase (Endo N) intracerebroventricularly to examine the effects of
      polysialic acid removal on sleep-wakefulness states and electroencephalogram
      (EEG) slow waves at both baseline and during recovery from 6 h of sleep
      deprivation. Endo N-treated rats showed a small but significant decrease in
      baseline rapid eye movement (REM) sleep selectively in the late light phase, and
      a facilitated REM sleep rebound after sleep deprivation, as compared with saline
      injected controls. Non-REM sleep and wakefulness were unaffected by Endo N. These
      results suggest that PSA NCAM is not particularly involved in the regulation of
      wakefulness or non-REM sleep, but plays a role in the diurnal pattern of REM
      sleep as well as in some aspects of REM sleep homeostasis.

PMID- 20128855
TI  - The relation of ventromedial prefrontal cortex activity and heart rate
      fluctuations at rest.
AB  - Recent studies applying functional magnetic resonance imaging have focused on the
      description of cerebral substrates of changes in cardiac function during diverse
      autonomic maneuvers or stressful cognitive tasks. These studies might be limited
      by the indistinguishable neuronal activity due to cognitive processes, which are
      known to influence autonomic function, and the 'baseline' activity in the central
      autonomic network. We therefore investigated 26 healthy volunteers in the
      magnetic resonance scanner to simultaneously obtain functional brain images and
      RR intervals (intervals between ventricular depolarizations) of the high
      resolution electrocardiogram. The mean RR interval length within each functional
      scan was computed, which was finally convolved with the canonical hemodynamic
      response function to obtain a regressor for the functional time series. The
      resulting individual contrast image indicated a positive covariation of the blood
      oxygen level-dependent signal and RR interval length in the ventromedial
      prefrontal cortex (vmPFC). Furthermore, a reduced mean cross-approximate entropy
      value was shown for the interaction between the vmPFC and individual RR
      intervals. This suggests reduced asynchrony between the heart rate and vmPFC
      activity in contrast to other brain areas. Our findings confirm data obtained in
      animals describing the vmPFC as an important forebrain structure of the central
      autonomic network and an influence of the vmPFC in the cortical generation of
      efferent vagal activity. This finding needs to be investigated in diseases with
      known suppression of efferent vagal modulation.

PMID- 20128856
TI  - Characterization of oculomotor and visual activities in the primate
      pedunculopontine tegmental nucleus during visually guided saccade tasks.
AB  - The pedunculopontine tegmental nucleus (PPTN) has anatomical connections with
      numerous visuomotor areas including the basal ganglia, thalamus, superior
      colliculus and frontal eye field. Although many anatomical and physiological
      studies suggest a role for the PPTN in the control of conditioned behavior and
      associative learning, the detailed characteristics of saccade- and visual-related
      activities of PPTN neurons remain unclear. We recorded the activity of PPTN
      neurons in monkeys (Macaca fuscata ) during visually guided saccade tasks, and
      examined the response properties of saccade- and visual-related activities such
      as time course, direction selectivity and contextual modulation. Saccade-related
      activity occurred either during saccade execution or after saccade end. The
      preferred directions of the neuronal activity were biased toward the
      contralateral and upward sides. Half of the saccade-related neurons showed
      activity modulation only for task saccades and not for spontaneous saccades
      outside the task. Visually-responsive neurons responded with short latencies.
      Some responded to the appearance of the visual stimulus in a directionally
      selective manner, and others responded to both the appearance and disappearance
      of the visual stimulus in a directionally non-selective manner. Many of these
      neurons exhibited distinct visual responses to the appearance of two different
      stimuli presented under different stages of the task, whereas a population of the
      neurons responded equally to the disappearance of the two stimuli. Thus, many
      PPTN neurons exhibited context-dependent activity related to the visuomotor
      events, consistent with a role in controlling conditioned behavior.

PMID- 20128857
TI  - Neurotoxic catecholamine metabolite in nociceptors contributes to painful
      peripheral neuropathy.

PMID- 20128858
TI  - Heparin-induced non-necrotizing skin lesions: rarely associated with heparin
      induced thrombocytopenia.
AB  - SUMMARY BACKGROUND: Recently, there has been an increasing number of reports
      regarding adverse skin reactions to subcutaneous heparin administration. Case
      series have implied that heparin-induced skin lesions are predominantly
      associated with life-threatening heparin-induced thrombocytopenia (HIT) in at
      least 22% of patients. Skin lesions, therefore, have been included in clinical
      scores for HIT. OBJECTIVES: To determine the association of heparin-induced skin
      lesions with HIT. This would have a pivotal impact on further anticoagulatory
      management in patients with heparin-induced skin lesions. PATIENTS/METHODS: In
      our observational cohort study, 87 consecutive patients with heparin-induced skin
      lesions (85 occurring during low-molecular-weight heparin administration) were
      evaluated using a standardized internal protocol, including HIT diagnostics
      (heparin-platelet factor 4-ELISA, heparin-induced platelet activation assay),
      platelet count monitoring, clinical/sonographical screening for thrombosis, skin
      allergy testing and, if necessary, histology. RESULTS: None of the observed
      heparin-induced skin lesions was due to HIT; all lesions were caused by delayed
      type IV-hypersensitivity reactions (DTH) instead. Even the cutaneous reaction in
      one patient with concomitant HIT could be classified histologically as DTH
      reaction, amounting to an association of heparin-induced skin lesions and HIT in
      1.2% (1/87; 95% confidence interval, 0.00-0.06). CONCLUSION: Heparin-induced skin
      lesions associated with use of low-molecular-weight heparins do not seem to be
      strongly associated with a systemic immunologic reaction in terms of HIT and
      might rather be due to DTH reactions than due to microvascular thrombosis. Hence,
      we propose refining existing pretest probability scores for HIT, unless
      underlying causes have been clarified.

PMID- 20128859
TI  - Incidence and risk factors for pulmonary embolism in the postpartum period.
AB  - SUMMARY BACKGROUND: Pregnancy and the postpartum period are times of
      hypercoagulability, increasing the risk of pulmonary embolism. Better
      quantification of risk factors can help target women who are most likely to
      benefit from postpartum thromboprophylaxis with heparin. OBJECTIVES: To determine
      the incidence rate and timing of postpartum pulmonary embolism, and assess
      perinatal risk factors predictive of the event. PATIENTS/METHODS: Antenatal,
      delivery and postpartum admission records of a cohort of 510 889 pregnancies were
      analysed. Pulmonary embolism was identified from ICD-10 codes at delivery,
      transfer or upon readmission at any time in the postpartum period. RESULTS:
      Pulmonary embolism occurred in 375 women and was most common postpartum. The rate
      of postpartum pulmonary embolism without an antecedent thrombotic event was 0.45
      per 1000 births. By the end of 4 weeks postpartum, the weekly rate approached the
      background rate of pulmonary embolism in the population. Although the Caesarean
      section rate rose significantly throughout the study period, and pulmonary
      embolism was more common following abdominal birth, the rate of pulmonary
      embolism following Caesarean birth fell. Regression modelling demonstrated that
      stillbirth (adjusted odds ratio [aOR] =5.97), lupus (aOR = 8.83) and transfusion
      of a coagulation product (aOR = 8.84) were most strongly associated with
      pulmonary embolism postpartum. CONCLUSIONS: Pulmonary embolism most commonly
      occurs up to 4 weeks postpartum and following abdominal birth. Despite this the
      absolute event rate is low and a broadly inclusive risk factor approach to the
      use of pharmacological thromboprophylaxis will require many women to be exposed
      to heparin to prevent an embolic event.

PMID- 20128860
TI  - Problems in laboratory testing: hemophilia and beyond.

PMID- 20128862
TI  - Platelet pharmacogenomics.
AB  - Platelet responsiveness to conventional antiplatelet therapy underlies a high
      interindividual variability influenced by various factors. For instance,
      antiplatelet therapy does not curtail the expected effects in a relevant number
      of patients as demonstrated by the occurrence of repeated cardiovascular events
      including stent thrombosis and/or by inadequate platelet inhibition measured by
      in vitro platelet function assays. Besides non-genetic factors such as age,
      gender, liver and renal function and co-medication, considerable variation of
      antiplatelet drug responsiveness can be attributed to genetic factors including
      polymorphisms and genetic variants of platelet surface proteins and drug
      metabolizing enzymes. Nowadays, platelet pharmacogenomics has started a new field
      with the goal to link genetic information of various drug targets to
      interindividual variability of drug response. Evolving data from large cohort
      studies suggest a promising role for pharmacogenomics in the context of
      antiplatelet therapy. Additionally, with the revolution of low cost and high
      throughput genotyping techniques, genetic testing has become affordable for
      clinical application and individualization of therapy. However, a key issue to
      define the future role of pharmacogenomics will rely on the benefit and the
      timeliness of implementing the genetic information into therapeutic decision.
      Hence, it warrants further investigations to document the prognostic effects of
      therapeutic alterations in distinct genotypes. Concerning the safety profile of
      emerging antiplatelet and antithrombotic drugs in certain risk groups it would be
      fatal to individualize treatment barely on behalf of an atherothrombotic
      genotype. In contrast, individual risk assessment combining non-genetic
      information and pharmacogenetic analysis represents a reasonable concept. Here,
      we provide a review on current data describing the role of pharmacogenomics in
      the field of antiplatelet drug treatment in cardiovascular patients with future
      directions.

PMID- 20128861
TI  - Comparative performance of gene-based warfarin dosing algorithms in a multiethnic
      population.
AB  - SUMMARY BACKGROUND: Gene-based warfarin dosing algorithms have largely been
      developed in homogeneous populations, and their generalizability has not been
      established. OBJECTIVES: We sought to assess the performance of published
      algorithms in a racially diverse and multiethnic sample, and determine if
      additional clinical variables or genetic variants associated with dose could
      enhance algorithm performance. PATIENTS AND METHODS: In 145 compliant patients on
      warfarin with a goal international normalized ratio (INR) of 2-3, stable,
      therapeutic doses were compared with predicted doses using 12 reported algorithms
      that incorporated CYP2C9 and VKORC1 variants. Additional covariates tested with
      each model included race, concurrent medications, medications known to interact
      with warfarin and previously described CYP4F2, CALU and GGCX variants. RESULTS:
      The mean patient age was 67 +/- 14 years; 90 (62%) were male. Eighty-two (57%)
      were Caucasian, 28 (19%) African-American, 20 (14%) Hispanic and 15 (10%) Asian.
      The median warfarin dose was 35 mg per week (interquartile range 23-53 mg per
      week). Gene-based dosing algorithms explained 37-55% of the variation in warfarin
      dose requirements. Neither the addition of race, number of concurrent medications
      nor the number of concurrent medications interacting with warfarin enhanced
      algorithm performance. Similarly, consideration of CYP4F2, CALU or GGCX variant
      genotypes did not improve algorithms. CONCLUSIONS: Existing gene-based dosing
      algorithms explained between approximately one-third and one-half of the
      variability in warfarin dose requirements in this racially and ethnically diverse
      cohort. Additional clinical and recently described genetic variants associated
      with warfarin dose did not enhance prediction in our patient population.

PMID- 20128863
TI  - Serum osteoprotegerin, sRANKL and carotid plaque formation and growth in a
      general population--the Tromso study.
AB  - SUMMARY BACKGROUND: Intervention studies in animal models suggest that
      osteoprotegerin (OPG) functions as an inhibitor or marker of atherosclerosis,
      whereas one prospective epidemiological study in humans indicated that OPG was an
      independent risk factor for progression of atherosclerosis. OBJECTIVE: To study
      the association between serum levels of OPG, soluble RANK ligand (sRANKL) and
      carotid artery plaque formation and plaque growth. PATIENTS/METHODS: The
      prevalence of carotid plaque and plaque area were assessed by ultrasonographic
      imaging at baseline and after 7 years follow-up in 2191 men and 2329 women who
      participated in a population-based study. RESULTS: OPG was significantly
      associated with atherosclerotic plaque burden and cardiovascular risk factors
      such as age, body mass index, blood pressure, total cholesterol, HDL cholesterol,
      HbA1c and fibrinogen at baseline, but not with sRANKL. In subjects without plaque
      at baseline, OPG predicted plaque formation in crude analysis in both women and
      men, but not after adjustment for age and other atherosclerotic risk factors. OPG
      predicted plaque growth in women (+1.8 mm(2), 0.6-3.0) (mean, 95% CI) per 1 SD
      increase in OPG (P = 0.003), whereas no associations were demonstrated in men
      (0.1 mm(2) (-1.3-1.4), P = 0.93). Soluble RANKL did not predict plaque formation
      or plaque growth. CONCLUSIONS: OPG was an independent predictor of plaque growth
      in women, but not in men, suggesting gender-specific actions of OPG in plaque
      growth. OPG was not associated with novel plaque formation.

PMID- 20128864
TI  - Involvement of the contact phase and intrinsic pathway in herpes simplex virus
      initiated plasma coagulation.
AB  - SUMMARY BACKGROUND: A hemostatic response to vascular injury is initiated by the
      extrinsic pathway of coagulation and amplified by the intrinsic pathway. We
      previously reported that purified herpes simplex virus type-1 (HSV1) has
      constitutive extrinsic pathway tissue factor (TF) and anionic phospholipid on its
      surface derived from the host cell, and can consequently bypass strict cellular
      control of coagulation. OBJECTIVE: The current work addresses the hypothesis that
      HSV1-induced plasma coagulation also involves intrinsic pathway, factor VIII
      (FVIII), and upstream contact activation pathway, factor XII (FXII). RESULTS:
      HSV1-initiated clotting was accelerated when purified FVIII was added to FVIII
      deficient plasma and in normal plasma attenuated by an inhibitory anti-FVIII
      antibody (Ab). High HSV1 concentrations predictably reduced the effect of FVIII
      due to the availability of excess viral TF. To further define TF-independent
      clotting mechanisms initiated by HSV1, the extrinsic pathway was disabled using
      factor VII-deficient plasma. The intrinsic pathway is triggered by activation of
      FXII associated with surface-bound kallikrein, which subsequently activates
      factor XI. Here we found that an inhibitor of activated FXII, corn trypsin
      inhibitor, and anti-FXII, anti-kallikrein and anti-FXI Abs inhibited HSV1
      initiated clotting. HSV1-enhanced activation of purified FXII was confirmed by
      Western blot, but required prekallikrein. CONCLUSION: The current work shows that
      HSV1 can trigger and amplify coagulation through the contact phase and intrinsic
      pathway, and suggests an additional mechanism that may contribute to vascular
      pathology.

PMID- 20128866
TI  - What has been learnt from the thrombin-activatable fibrinolysis inhibitor
      deficient mouse?
AB  - SUMMARY: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a circulating
      zymogen that is activated physiologically by the thrombin/thrombomodulin complex
      to activated TAFI (TAFIa) which is a basic carboxypeptidase. Substrates include
      fibrin, leading to a reduction in rate of plasmin generation, and several
      proinflammatory mediators such as bradykinin, thrombin-cleaved osteopontin and
      complement factor C5a. TAFI-deficient mice have no phenotype without being
      challenged and TAFIa appears to play a limited role in physiological fibrinolysis
      in vivo. In several disease models, the TAFI-deficient mice have different
      outcomes from the wild type (WT), but whether the difference is beneficial or an
      exacerbation of the disease depends on the model. The consequences of TAFI
      deficiency include increased plasmin as a result of enhanced incorporation of
      plasminogen and tissue plasminogen activator into the fibrin clot, but also loss
      of its ability to degrade other substrates, with the resultant up-regulation of
      several proinflammatory mediators, including C5a. Criteria are recommended to
      demonstrate that a substrate is a physiological substrate of TAFIa.

PMID- 20128867
TI  - High platelet reactivity is associated with myocardial infarction in
      premenopausal women: a population-based case-control study.
AB  - SUMMARY BACKGROUND: Platelets are involved in the occlusion of coronary arteries
      after rupture of an atherosclerotic plaque. Furthermore, activated platelets
      release large quantities of growth factors, chemokines and interleukins that
      regulate inflammatory reactions. Therefore, we hypothesized that high basal
      platelet reactivity may contribute to an increased risk of myocardial infarction
      (MI) in premenopausal women. METHODS: We assessed the relation between high
      platelet reactivity and MI in a population-based case-control study among
      premenopausal women (aged < 50 years). We used multivariable logistic regression
      to quantify the effect of high platelet reactivity, adjusted for potential
      confounders. Platelet reactivity was estimated by plasma levels of neutrophil
      activating peptide 2 (NAP-2), CXC chemokine ligand (CXCL)4, soluble glycoprotein
      1b (sGPIb) and soluble P-selectin. RESULTS: High platelet reactivity (i.e. levels
      >or= 90th percentile control subjects) was associated with a 2- to 3-fold
      increased incidence of MI: the adjusted odds ratios (ORs) were 3.0 [95%
      confidence interval (CI) 1.4-6.4] for NAP-2, 2.2 (0.9-5.1) for CXCL4, 1.9 (0.7
      4.6) for sP-selectin and 2.5 (1.1-5.7) for sGPIb. The incidence of MI dose
      dependently increased when more markers were elevated. High platelet reactivity
      according to both NAP-2 and sGPIb was associated with an up to tenfold increased
      incidence (9.9, 95% confidence interval 2.0-48.3). CONCLUSIONS: High basal
      platelet reactivity was associated with a 2- to 3-fold higher incidence of MI
      compared with normal platelet reactivity in premenopausal women. Our results
      suggest that high basal platelet reactivity may contribute to a higher risk of
      MI.

PMID- 20128868
TI  - The pro-apoptotic BH3-only protein Bim regulates cell cycle progression of
      hematopoietic progenitors during megakaryopoiesis.
AB  - SUMMARY BACKGROUND: The pro-apoptotic BH3-only protein Bim is recognized as a
      pivotal regulator of apoptosis induced by the depletion of cytokines. In the
      present study, we examined the role of Bim in megakaryopoiesis. METHODS:
      Megakaryocyte (MK) progenitors obtained from bim knockout (KO) mice were analyzed
      in vitro for liability to apoptosis after the depletion of cytokines, ability to
      differentiate into MKs and proliferation/cell cycle progression in response to
      thrombopoietin (TPO). The production of platelets in vitro was evaluated by
      assaying the formation of proplatelets in MKs. Megakaryopoiesis in vivo was
      observed in a mouse model of thrombocytopenia induced by injecting fluorouracil
      (5-FU). RESULTS: Bim-deficient CD34-/c-kit+/Sca-1+/Lineage- stem cells and MKs
      were highly resistant to apoptosis induced by cytokine depletion, suggesting that
      Bim is involved in the apoptotic process in both stem cells and MKs. As bim KO
      mice exhibited splenomegaly and thrombocytopenia, splenectomized mice were used
      for experiments in vivo. Platelet recovery after 5-FU-induced thrombocytopenia
      was significantly delayed in bim KO mice. Corresponding with this, numbers of MKs
      in the recovery phase bone marrow were significantly reduced in bim KO mice.
      Culture of c-kit+/Lineage- progenitors with TPO revealed that Bim-deficient cells
      poorly proliferate and differentiate into CD41+ cells in comparison with wild
      type (WT) cells. However, once differentiated into MKs, these cells matured
      normally. Furthermore, cell cycle analyses demonstrated that transition from the
      G1 to the S phase was delayed in Bim-deficient stem cells. CONCLUSIONS: In the
      present study, we demonstrated that Bim plays a pivotal role in the regulation of
      cell cycle progression in hepatopoietic progenitors during megakaryopiesis.

PMID- 20128869
TI  - Reversal of warfarin-induced over-anticoagulation with individualized dosing of
      oral vitamin K: a pilot study.

PMID- 20128870
TI  - D-dimer testing in pregnant patients: towards determining the next 'level' in the
      diagnosis of deep vein thrombosis.
AB  - SUMMARY BACKGROUND: The role of D-dimer in excluding deep vein thrombosis (DVT)
      in pregnancy is currently uncertain. We hypothesized that the specificity of
      sensitive D-dimer assays could be improved without compromising sensitivity by
      using higher D-dimer cut-off values. OBJECTIVE: To determine the test
      characteristics of two rapid enzyme-linked immunosorbent assays and three latex
      agglutination assays in pregnancy. METHOD: We recruited consecutive pregnant
      women who presented to participating centers with suspected DVT for the study.
      Symptomatic women were investigated with compression ultrasonography, and
      received 3 months of clinical follow-up to assess for the presence of venous
      thrombosis. Plasma samples for D-dimer were collected and frozen at the time of
      presentation. The median and mean D-dimer values for respective trimesters of
      pregnancy in patients with and without DVT were calculated. Receiver operating
      curves (ROCs) were plotted for respective assays to establish the best cut
      points. The test characteristics corresponding to standard cut-points and these
      'pregnancy' cut-points are presented. RESULTS: The prevalence of DVT in our
      cohort was 6.6% (95% confidence interval 4.0-10.6%). The mean and median D-dimer
      values were significantly increased throughout pregnancy. Overall, women with
      confirmed DVT had higher D-dimer levels than women without DVT (P < 0.0001).
      Improved specificities (62-79%) were observed with the use of higher cut-points
      obtained from ROCs for all five assays, and high sensitivities were maintained
      (80-100%) for DVT diagnosis. CONCLUSION: Using higher cut-points than those used
      in non-pregnant patients, the specificity of D-dimer assays for the diagnosis of
      DVT in pregnancy can be improved without compromising sensitivity. Validation in
      prospective management studies is needed.

PMID- 20128871
TI  - Gene variants associated with venous thrombosis: confirmation in the MEGA study.

PMID- 20128873
TI  - Stepping up melanocytes to the challenge of UV exposure.
AB  - Exposure to solar ultraviolet radiation (UV) is the main etiological factor for
      skin cancer, including melanoma. Cutaneous pigmentation, particularly eumelanin,
      afforded by melanocytes is the main photoprotective mechanism, as it prevents UV
      induced DNA damage in the epidermis. Therefore, maintaining genomic stability of
      melanocytes is crucial for prevention of melanoma, as well as keratinocyte
      derived basal and squamous cell carcinoma. A critical independent factor for
      preventing melanoma is DNA repair capacity. The response of melanocytes to UV is
      mediated mainly by a network of paracrine factors that not only activate
      melanogenesis, but also DNA repair, anti-oxidant, and survival pathways that are
      pivotal for maintenance of genomic stability and prevention of malignant
      transformation or apoptosis. However, little is known about the stress response
      of melanocytes to UV and the regulation of DNA repair pathways in melanocytes.
      Unraveling these mechanisms might lead to strategies to prevent melanoma, as well
      as non-melanoma skin cancer.

PMID- 20128874
TI  - How blocking Raf activates the MAPK pathway.

PMID- 20128876
TI  - Programming T cells for adoptive T cell transfer therapy.

PMID- 20128875
TI  - Roles of endothelin signaling in melanocyte development and melanoma.
AB  - Endothelin (Edn) signaling via the G-coupled, Edn receptor type B (Ednrb) is
      essential for the development of melanocytes from the neural crest (NC) and has
      been associated with melanoma progression. Edn3 plays varying roles during
      melanocyte development, promoting the proliferation and self-renewal of NC
      derived multi- and bi-potential precursors as well as the survival,
      proliferation, differentiation and migration of committed melanocyte precursors.
      Melanocyte differentiation is achieved via the interaction of Ednrb and Kit
      signaling, with Ednrb being specifically required in the final differentiation
      step, rather than in the initial specification of melanocytic fate. Ednrb has
      also been implicated in the de-differentiation of mature melanocytes, a process
      that takes place during the malignant transformation of these cells. Ednrb was
      found to be upregulated in melanoma metastases and was shown to alter tumor-host
      interactions leading to melanoma progression. Antagonists to this receptor were
      shown to inhibit melanoma cell growth and increase the apoptotic rate of these
      cells, and to lead to disease stabilization in melanoma patients. Thus, Edn
      signaling inhibition may prove useful in the treatment of certain types of
      melanoma.

PMID- 20128877
TI  - Ozone-triggered rapid stomatal response involves the production of reactive
      oxygen species, and is controlled by SLAC1 and OST1.
AB  - The air pollutant ozone can be used as a tool to unravel in planta processes
      induced by reactive oxygen species (ROS). Here, we have utilized ozone to study
      ROS-dependent stomatal signaling. We show that the ozone-triggered rapid
      transient decrease (RTD) in stomatal conductance coincided with a burst of ROS in
      guard cells. RTD was present in 11 different Arabidopsis ecotypes, suggesting
      that it is a genetically robust response. To study which signaling components or
      ion channels were involved in RTD, we tested 44 mutants deficient in various
      aspects of stomatal function. This revealed that the SLAC1 protein, essential for
      guard cell plasma membrane S-type anion channel function, and the protein kinase
      OST1 were required for the ROS-induced fast stomatal closure. We showed a
      physical interaction between OST1 and SLAC1, and provide evidence that SLAC1 is
      phosphorylated by OST1. Phosphoproteomic experiments indicated that OST1
      phosphorylated multiple amino acids in the N terminus of SLAC1. Using TILLING we
      identified three new slac1 alleles where predicted phosphosites were mutated. The
      lack of RTD in two of them, slac1-7 (S120F) and slac1-8 (S146F), suggested that
      these serine residues were important for the activation of SLAC1. Mass
      spectrometry analysis combined with site-directed mutagenesis and phosphorylation
      assays, however, showed that only S120 was a specific phosphorylation site for
      OST1. The absence of the RTD in the dominant-negative mutants abi1-1 and abi2-1
      also suggested a regulatory role for the protein phosphatases ABI1 and ABI2 in
      the ROS-induced activation of the S-type anion channel.

PMID- 20128878
TI  - Rice metal-nicotianamine transporter, OsYSL2, is required for the long-distance
      transport of iron and manganese.
AB  - Rice (Oryza sativa) is indispensable in the diet of most of the world's
      population. Thus, it is an important target in which to alter iron (Fe) uptake
      and homeostasis, so as to increase Fe accumulation in the grain. We previously
      isolated OsYSL2, a functional iron [Fe(II)]- and manganese [Mn(II)]-nicotianamine
      complex transporter that is expressed in phloem cells and developing seeds. We
      produced RNAi (OsYSL2i) and overexpression lines (OXOsYSL2) of OsYSL2. At the
      vegetative stage in an OsYSL2i line, the Fe and Mn concentrations were decreased
      in the shoots, and the Fe concentration was increased in the roots. At the
      reproductive stage, positron-emitting tracer imaging system analysis revealed
      that Fe translocation to the shoots and seeds was suppressed in OsYSL2i. The Fe
      and Mn concentrations were decreased in the seeds of OsYSL2i, especially in the
      endosperm. Moreover, the Fe concentration in OXOsYSL2 was lower in the seeds and
      shoots, but higher in the roots, compared with the wild type. Furthermore, when
      OsYSL2 expression was driven by the sucrose transporter promoter, the Fe
      concentration in the polished rice was up to 4.4-fold higher compared with the
      wild type. These results indicate that the altered expression of OsYSL2 changes
      the localization of Fe, and that OsYSL2 is a critical Fe-nicotianamine
      transporter important for Fe translocation, especially in the shoots and
      endosperm.

PMID- 20128879
TI  - The DDB1a interacting proteins ATCSA-1 and DDB2 are critical factors for UV-B
      tolerance and genomic integrity in Arabidopsis thaliana.
AB  - The integrity of the genome is a fundamental prerequisite for the well-being of
      all living organisms. Critical for the genomic integrity are effective DNA damage
      detection mechanisms that enable the cell to rapidly activate the necessary
      repair machinery. Here, we describe Arabidopsis thaliana ATCSA-1, which is an
      ortholog of the mammalian Cockayne Syndrome type-A protein involved in
      transcription-coupled DNA repair processes. ATCSA-1 is a critical component for
      initiating the repair of UV-B-induced DNA lesions, and, together with the damage
      specific DNA binding protein 2 (DDB2), is necessary for light-independent repair
      processes in Arabidopsis. The transcriptional profile of both genes revealed that
      ATCSA-1 is strongly expressed in most tissues, whereas DDB2 is only weakly
      expressed, predominantly in the root tips and anthers of flowers. In contrast to
      ATCSA-1, DDB2 expression is rapidly inducible by UV treatment. Like DDB2, ATCSA-1
      is localized to the nucleus, and assembles with DDB1 and CUL4 proteins into a
      complex. ATCSA-1 is an unstable protein that is degraded in a 26S proteasome
      dependent manner. Overall, the results presented here form a functional
      description of a plant Cockayne syndrome factor A (CSA) ortholog, and demonstrate
      the importance of ATCSA-1 for UV-B tolerance.

PMID- 20128880
TI  - Mechanisms of leaf tooth formation in Arabidopsis.
AB  - Serration found along leaf margins shows species-specific characters. Whereas
      compound leaf development is well studied, the process of serration formation is
      largely unknown. To understand mechanisms of serration development, we
      investigated distinctive features of cells that could give rise to tooth
      protrusion in the simple-leaf plant Arabidopsis. After the emergence of a tooth,
      marginal cells, except for cells at the sinuses and tips, started to elongate
      rapidly. Localized cell division seemed to keep cells at the sinus smaller,
      rather than halt cell elongation. As leaves matured, the marginal cell number
      between teeth became similar in any given tooth. These results suggest that teeth
      are formed by repetition of an unknown mechanism that spatially monitors cell
      number and regulates cell division. We then examined the role of CUP-SHAPED
      COTYLEDON 2 (CUC2) in serration development. cuc2-3 forms fewer hydathodes and
      auxin maxima, visualized by DR5rev::GFP, at the leaf margin, suggesting that CUC2
      patterns serration through the regulation of auxin. In contrast to a previous
      interpretation, comparison of leaf outlines revealed that CUC2 promotes outgrowth
      of teeth rather than suppression of growth at the sinuses. We found that mutants
      with increased CUC2 expression form ectopic tissues and mis-express SHOOT
      MERISTEMLESS (STM) at the sinus between the enhanced teeth. Similar but
      infrequent STM expression was found in the wild type, indicating STM involvement
      in the serration of simple leaves. Our study provides insights into the
      morphological and molecular mechanisms for leaf development and tooth formation,
      and highlights similarities between serration and compound leaf development.

PMID- 20128881
TI  - Two widely expressed plasma membrane H(+)-ATPase isoforms of Nicotiana tabacum
      are differentially regulated by phosphorylation of their penultimate threonine.
AB  - The plasma membrane H(+)-ATPases PMA2 and PMA4 are the most widely expressed in
      Nicotiana plumbaginifolia, and belong to two different subfamilies. Both are
      activated by phosphorylation of a Thr at the penultimate position and the
      subsequent binding of 14-3-3 proteins. Their expression in Saccharomyces
      cerevisiae revealed functional and regulatory differences. To determine whether
      different regulatory properties between PMA2 and PMA4 exist in plants, we
      generated two monoclonal antibodies able to detect phosphorylation of the
      penultimate Thr of either PMA2 or PMA4 in a total protein extract. We also raised
      Nicotiana tabacum transgenic plants expressing 6-His-tagged PMA2 or PMA4,
      enabling their individual purification. Using these tools we showed that
      phosphorylation of the penultimate Thr of both PMAs was high during the early
      exponential growth phase of an N. tabacum cell culture, and then progressively
      declined. This decline correlated with decreased 14-3-3 binding and decreased
      plasma membrane ATPase activity. However, the rate and extent of the decrease
      differed between the two isoforms. Cold stress of culture cells or leaf tissues
      reduced the Thr phosphorylation of PMA2, whereas no significant changes in Thr
      phosphorylation of PMA4 were seen. These results strongly suggest that PMA2 and
      PMA4 are differentially regulated by phosphorylation. Analysis of the H(+)-ATPase
      phosphorylation status in leaf tissues indicated that no more than 44% (PMA2) or
      32% (PMA4) was in the activated state under normal growth conditions.
      Purification of either isoform showed that, when activated, the two isoforms did
      not form hetero-oligomers, which is further support for these two H(+)-ATPase
      subfamilies having different properties.

PMID- 20128882
TI  - Receptor-like kinase OsSIK1 improves drought and salt stress tolerance in rice
      (Oryza sativa) plants.
AB  - Receptor-like kinases (RLKs) play essential roles in plant growth, development
      and responses to environmental stresses. A putative RLK gene, OsSIK1, with
      extracellular leucine-rich repeats was cloned and characterized in rice (Oryza
      sativa). OsSIK1 exhibits kinase activity in the presence of Mn(2+), and the
      OsSIK1 kinase domain has the ability to autophosphorylate and phosphorylate
      myelin basic protein (MBP). OsSIK1 promoter-GUS analysis revealed that OsSIK1 is
      expressed mainly in the stem and spikelet in rice. The expression of OsSIK1 is
      mainly induced by salt, drought and H(2)O(2) treatments. Transgenic rice plants
      with overexpression of OsSIK1 show higher tolerance to salt and drought stresses
      than control plants. On the contrary, the knock-out mutants sik1-1 and sik1-2, as
      well as RNA interference (RNAi) plants, are sensitive to drought and salt
      stresses. The activities of peroxidase, superoxide dismutase and catalase are
      enhanced significantly in OsSIK1-overexpressing plants. Also, the accumulation of
      H(2)O(2) in leaves of OsSIK1-overexpressing plants is much less than that of the
      mutants, RNAi plants and control plants, as measured by 3,3'-diamino benzidine
      (DAB) staining. We also show that OsSIK1 affects stomatal density in the abaxial
      and adaxial leaf epidermis of rice. These results indicate that OsSIK1 plays
      important roles in salt and drought stress tolerance in rice, through the
      activation of the antioxidative system.

PMID- 20128883
TI  - ASKtheta, a group-III Arabidopsis GSK3, functions in the brassinosteroid
      signalling pathway.
AB  - Brassinosteroids (BRs) are plant hormones that regulate many processes including
      cell elongation, leaf development, pollen tube growth and xylem differentiation.
      GSK3/shaggy-like kinases (GSK) are critical regulators of intracellular
      signalling initiated by the binding of BR to the BRI1 receptor complex. Three
      GSKs have already been shown to relay BR responses, including phosphorylation of
      the transcriptional regulator BES1. However, recent studies indicate that one or
      more yet unidentified protein kinases are involved in BR signalling. Here, we
      show that the in vivo protein kinase activity of the group-III GSK, ASKtheta, was
      negatively regulated by BRI1. Arabidopsis thaliana plants with enhanced ASKtheta
      activity displayed a bri1-like phenotype. ASKtheta overexpressors accumulated
      high levels of brassinolide, castasterone and typhasterol, and were insensitive
      to BR. ASKtheta localized to the nucleus and directly phosphorylated BES1 and
      BZR1. Moreover, the BES1/BZR1-like transcription factor BEH2 was isolated as an
      ASKtheta interaction partner in a yeast two-hybrid screen. ASKtheta
      phosphorylated BEH2 both in vitro and in vivo. Overall, these data provide strong
      evidence that ASKtheta is a novel component of the BR signalling cascade,
      targeting the transcription factors BES1, BZR1 and BEH2.

PMID- 20128884
TI  - Polerovirus protein P0 prevents the assembly of small RNA-containing RISC
      complexes and leads to degradation of ARGONAUTE1.
AB  - RNA silencing plays an important role in plants in defence against viruses. To
      overcome this defence, plant viruses encode suppressors of RNA silencing. The
      most common mode of silencing suppression is sequestration of double-stranded
      RNAs involved in the antiviral silencing pathways. Viral suppressors can also
      overcome silencing responses through protein-protein interaction. The poleroviral
      P0 silencing suppressor protein targets ARGONAUTE (AGO) proteins for degradation.
      AGO proteins are the core component of the RNA-induced silencing complex (RISC).
      We found that P0 does not interfere with the slicer activity of pre-programmed
      siRNA/miRNA containing AGO1, but prevents de novo formation of siRNA/miRNA
      containing AGO1. We show that the AGO1 protein is part of a high-molecular-weight
      complex, suggesting the existence of a multi-protein RISC in plants. We propose
      that P0 prevents RISC assembly by interacting with one of its protein components,
      thus inhibiting formation of siRNA/miRNA-RISC, and ultimately leading to AGO1
      degradation. Our findings also suggest that siRNAs enhance the stability of co
      expressed AGO1 in both the presence and absence of P0.

PMID- 20128885
TI  - microRNA-directed cleavage and translational repression of the copper chaperone
      for superoxide dismutase mRNA in Arabidopsis.
AB  - microRNA398 (miR398) is a conserved miRNA of plants that targets two of the three
      copper/zinc superoxide dismutases (SOD) of Arabidopsis (CSD1 and CSD2) by
      triggering cleavage or inhibiting translation of their mRNAs. We analysed the
      transcriptomes of mutants impaired in miR398 production, and found that the mRNAs
      encoding the copper chaperone for superoxide dismutase (CCS1), which delivers
      copper to CSD1 and CSD2 apoproteins in different cellular compartments, are
      undiscovered targets of miR398. We identified the cleavage site in CCS1 mRNAs by
      5'-RACE PCR. We further show that both CCS1 protein and mRNA levels are tightly
      linked to the quantities of miR398, which are themselves dependent on the copper
      content in the medium. We generated transgenic plants carrying a CCS1 mRNA
      version resistant to cleavage by miR398, and demonstrated that both CCS1 mRNAs
      and proteins accumulate in these plants when miR398 is abundant and copper
      limiting. Moreover, we show that one of the ten ARGONAUTE proteins of Arabidopsis
      (AGO10) is involved in miR398-directed translational inhibition of CCS1 mRNAs, as
      CCS1 protein, but not CCS1 mRNAs accumulates in ago10 (zll) mutants. Thus, miR398
      mediates the cleavage and translational inhibition of mRNAs encoding CCS1, the
      chaperone protein that is essential for generating the mature copper/zinc SODs of
      Arabidopsis. Our results also imply that new targets that have not been
      identified by computing analyses have yet to be discovered, even for an
      extensively studied miRNA such as miR398.

PMID- 20128886
TI  - A secreted effector protein (SNE1) from Phytophthora infestans is a broadly
      acting suppressor of programmed cell death.
AB  - Evasion or active suppression of host defenses are critical strategies employed
      by biotrophic phytopathogens and hemibiotrophs whose infection mechanism includes
      sequential biotrophic and necrotrophic stages. Although defense suppression by
      secreted effector proteins has been well studied in bacteria, equivalent systems
      in fungi and oomycetes are poorly understood. We report the characterization of
      SNE1 (suppressor of necrosis 1), a gene encoding a secreted protein from the
      hemibiotrophic oomycete Phytophthora infestans that is specifically expressed at
      the transcriptional level during biotrophic growth within the host plant tomato
      (Solanum lycopersicum). Using transient expression assays, we show that SNE1
      suppresses the action of secreted cell death-inducing effectors from Phytophthora
      that are expressed during the necrotrophic growth phase, as well as programmed
      cell death mediated by a range of Avr-R protein interactions. We also report that
      SNE1 contains predicted NLS motifs and translocates to the plant nucleus in
      transient expression studies. A conceptual model is presented in which the
      sequential coordinated secretion of antagonistic effectors by P. infestans first
      suppresses, but then induces, host cell death, thereby providing a highly
      regulated means to control the transition from biotrophy to necrotrophy.

PMID- 20128888
TI  - A functional polymorphism in the DNA methyltransferase-3A promoter modifies the
      susceptibility in gastric cancer but not in esophageal carcinoma.
AB  - BACKGROUND: DNA-methyltransferase (DNMT)-3A plays an important role in the
      development of embryogenesis and the generation of aberrant methylation in
      carcinogenesis. The aim of this study was to investigate the role of a DNMT3A
      promoter genetic variant on its transcriptional activity and to evaluate the
      association between DNMT3A gene polymorphism and the susceptibility to gastric
      cancer (GC) and oesophagus carcinoma (EC) in the Chinese population. METHODS: We
      selected one of the single nucleotide polymorphisms (SNPs) -448A>G in the DNMT3A
      promoter region and evaluated its effect on activity using a luciferase assay. 
      448A>G polymorphisms of DNMT3A were determined by polymerase chain
      reaction/restriction fragment length polymorphism and confirmed by sequencing.
      The distribution of -448A>G polymorphisms was detected in 208 GC patients and 346
      healthy controls matched for age and gender. The distribution of -448A>G
      polymorphisms was also detected in 96 EC patients and matched 241 healthy
      controls. The association of -448A>G polymorphisms of DNMT3A and the risk of GC
      and EC was evaluated by stratified analysis according to the patient's age and
      gender. RESULTS: In a promoter assay, carriage of the -448 A allele showed a
      significantly higher promoter activity (> two fold) compared with the -448G
      allele (P < 0.001). The allele frequency of -448A among GC patients and controls
      was 32.9% versus 19.9%, respectively. Overall, we found that, compared with GG
      carriers, the DNMT3A -448AA homozygotes has a > six fold increased risk of GC.
      Stratification analysis showed that AA homozygotes have a more profound risk in
      the subgroups of individuals at the age range <or= 60 years in GC. However,
      individuals with -448AG and -448AA were not statistically significantly
      associated with an increased risk of EC compared with those carried the -448GG
      genotype. CONCLUSIONS: The DNMT3A -448A>G polymorphism is a novel functional SNP
      and contributes to its genetic susceptibility to GC. -448A>G can be used as a
      stratification marker to predict an individual's susceptibility to GC, especially
      in the subgroups of individuals at the age range <or= 60 years. However, the
      relative distribution of -448A>G in EC can not be used as a prediction marker in
      order to evaluate an individual's susceptibility to EC.

PMID- 20128889
TI  - In vitro antifungal activity of hydroxychavicol isolated from Piper betle L.
AB  - BACKGROUND: Hydroxychavicol, isolated from the chloroform extraction of the
      aqueous leaf extract of Piper betle L., (Piperaceae) was investigated for its
      antifungal activity against 124 strains of selected fungi. The leaves of this
      plant have been long in use tropical countries for the preparation of traditional
      herbal remedies. METHODS: The minimum inhibitory concentration (MIC) and minimum
      fungicidal concentration (MFC) of hydroxychavicol were determined by using broth
      microdilution method following CLSI guidelines. Time kill curve studies, post
      antifungal effects and mutation prevention concentrations were determined against
      Candida species and Aspergillus species "respectively". Hydroxychavicol was also
      tested for its potential to inhibit and reduce the formation of Candida albicans
      biofilms. The membrane permeability was measured by the uptake of propidium
      iodide. RESULTS: Hydroxychavicol exhibited inhibitory effect on fungal species of
      clinical significance, with the MICs ranging from 15.62 to 500 microg/ml for
      yeasts, 125 to 500 microg/ml for Aspergillus species, and 7.81 to 62.5 microg/ml
      for dermatophytes where as the MFCs were found to be similar or two fold greater
      than the MICs. There was concentration-dependent killing of Candida albicans and
      Candida glabrata up to 8 x MIC. Hydroxychavicol also exhibited an extended post
      antifungal effect of 6.25 to 8.70 h at 4 x MIC for Candida species and suppressed
      the emergence of mutants of the fungal species tested at 2 x to 8 x MIC
      concentration. Furthermore, it also inhibited the growth of biofilm generated by
      C. albicans and reduced the preformed biofilms. There was increased uptake of
      propidium iodide by C. albicans cells when exposed to hydroxychavicol thus
      indicating that the membrane disruption could be the probable mode of action of
      hydroxychavicol. CONCLUSIONS: The antifungal activity exhibited by this compound
      warrants its use as an antifungal agent particularly for treating topical
      infections, as well as gargle mouthwash against oral Candida infections.

PMID- 20128887
TI  - Evaluation of a combined strategy directed towards health-care professionals and
      patients with chronic obstructive pulmonary disease (COPD): information and
      health education feedback for improving clinical monitoring and quality-of-life.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a health problem that
      is becoming increasingly attended-to in Primary Care (PC). However, there is a
      scarcity of health-care programs and studies exploring the implementation of
      Clinical Practice Guidelines (CPG). The principal objective of the present study
      is to evaluate the effectiveness of a combined strategy directed towards health
      care professionals and patients to improve the grade of clinical control and the
      quality-of-life (QoL) of the patients via a feedback on their state-of-health. A
      training plan for the health-care professionals is based on CPG and health
      education. METHOD/DESIGN: Multi-centred, before-after, quasi experimental,
      prospective study involving an intervention group and a control group of
      individuals followed-up for 12 months. The patients receive attention from urban
      and semi-urban Primary Care Centres (PCC) within the administrative area of the
      Costa de Ponent (near Barcelona). All the pacients corresponding to the PCC of
      one sub-area were assigned to the intervention group and patients from the rest
      of sub-areas to the group control. The intervention includes providing data to
      the health-care professionals (clinician/nurse) derived from a clinical history
      and an interview. A course of training focused on aspects of CPG, motivational
      interview and health education (tobacco, inhalers, diet, physical exercise,
      physiotherapy). The sample random includes a total of 801 patients (> or = 40
      years of age), recorded as having COPD, receiving attention in the PCC or at
      home, who have had at least one clinical visit, and who provided written informed
      consent to participation in the study. Data collected include socio-demographic
      characteristics, drug treatment, exacerbations and hospital admissions,
      evaluation of inhaler use, tobacco consumption and life-style and health-care
      resources consumed. The main endpoints are dyspnoea, according to the modified
      scale of the Medical Research Council (MRC) and the QoL, evaluated with the St
      George's Respiratory Questionnaire (SGRQ). The variables are obtained at the
      start and the end of the intervention. Information from follow-up visits focuses
      on the changes in life-style activities of the patient. DISCUSSION: This study is
      conducted with the objective of generating evidence that shows that
      implementation of awareness programs directed towards health-care professionals
      as well as patients in the context of PC can produce an increase in the QoL and a
      decrease in the disease exacerbation, compared to standard clinical practice.
      TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT00922545;

PMID- 20128890
TI  - Loss of balancing selection in the betaS globin locus.
AB  - BACKGROUND: Probably the best example of the rise and maintenance of balancing
      selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in
      protecting from malaria. Yet, the dynamics of such a process remains poorly
      understood, particularly in relation to different malaria transmission rates and
      the genetic background of the affected populations. METHODS: We investigated the
      association of haemoglobin HbS in protection from clinical episodes of malaria in
      two populations/villages where malaria is endemic, but mostly presenting in mild
      clinical forms. Five-hundred and forty-six individuals comprising 65 and 82
      families from the Hausa and Massalit villages respectively were genotyped for
      HbS. Allele and genotype frequencies as well as departure from Hardy-Weinberg
      Equilibrium were estimated from four-hundred and seventy independent genotypes
      across different age groups. Age-group frequencies were used to calculate the
      coefficient-of-fitness and to simulate the expected frequencies in future
      generations. RESULTS: Genotype frequencies were within Hardy-Weinberg
      expectations in Hausa and Massalit in the total sample set but not within the
      different age groups. There was a trend for a decrease of the HbS allele
      frequency in Hausa and an increase of frequency in Massalit. Although the HbS
      allele was able to confer significant protection from the clinical episodes of
      malaria in the two populations, as suggested by the odds ratios, the overall
      relative fitness of the HbS allele seems to have declined in Hausa. CONCLUSIONS:
      Such loss of balancing selection could be due to a combined effect of
      preponderance of non-clinical malaria in Hausa, and the deleterious effect of the
      homozygous HbS under circumstances of endogamy.

PMID- 20128891
TI  - Suicide amongst psychiatric in-patients who abscond from the ward: a national
      clinical survey.
AB  - BACKGROUND: Suicide prevention by mental health services requires an awareness of
      the antecedents of suicide amongst high risk groups such as psychiatric in
      patients. The goal of this study was to describe the social and clinical
      characteristics of people who had absconded from an in-patient psychiatric ward
      prior to suicide, including aspects of the clinical care they received. METHODS:
      We carried out a national clinical survey based on a 10-year (1997-2006) sample
      of people in England and Wales who had died by suicide. Detailed data were
      collected on those who had been in contact with mental health services in the
      year before death. RESULTS: There were 1,851 cases of suicide by current
      psychiatric in-patients, 14% of all patient suicides. 1,292 (70%) occurred off
      the ward. Four hundred and sixty-nine of these patients died after absconding
      from the ward, representing 25% of all in-patient suicides and 38% of those that
      occurred off the ward. Absconding suicides were characterised by being young,
      unemployed and homeless compared to those who were off the ward with staff
      agreement. Schizophrenia was the most common diagnosis, and rates of previous
      violence and substance misuse were high. Absconders were proportionally more
      likely than in-patients on agreed leave to have been legally detained for
      treatment, non-compliant with medication, and to have died in the first week of
      admission. Whilst absconding patients were significantly more likely to have been
      under a high level of observation, clinicians reported more problems in
      observation due to either the ward design or other patients on the ward.
      CONCLUSION: Measures that may prevent absconding and subsequent suicide amongst
      in-patients might include tighter control of ward exits, and more intensive
      observation of patients, particularly in the early days of admission. Improving
      the ward environment to provide a supportive and less intimidating experience may
      contribute to reduced risk.

PMID- 20128892
TI  - Identification and characterisation of CYP75A31, a new flavonoid 3'5'
      hydroxylase, isolated from Solanum lycopersicum.
AB  - BACKGROUND: Understanding the regulation of the flavonoid pathway is important
      for maximising the nutritional value of crop plants and possibly enhancing their
      resistance towards pathogens. The flavonoid 3'5'-hydroxylase (F3'5'H) enzyme
      functions at an important branch point between flavonol and anthocyanin
      synthesis, as is evident from studies in petunia (Petunia hybrida), and potato
      (Solanum tuberosum). The present work involves the identification and
      characterisation of a F3'5'H gene from tomato (Solanum lycopersicum), and the
      examination of its putative role in flavonoid metabolism. RESULTS: The cloned and
      sequenced tomato F3'5'H gene was named CYP75A31. The gene was inserted into the
      pYeDP60 expression vector and the corresponding protein produced in yeast for
      functional characterisation. Several putative substrates for F3'5'H were tested
      in vitro using enzyme assays on microsome preparations. The results showed that
      two hydroxylation steps occurred. Expression of the CYP75A31 gene was also tested
      in vivo, in various parts of the vegetative tomato plant, along with other key
      genes of the flavonoid pathway using real-time PCR. A clear response to nitrogen
      depletion was shown for CYP75A31 and all other genes tested. The content of rutin
      and kaempferol-3-rutinoside was found to increase as a response to nitrogen
      depletion in most parts of the plant, however the growth conditions used in this
      study did not lead to accumulation of anthocyanins. CONCLUSIONS: CYP75A31 (NCBI
      accession number GQ904194), encodes a flavonoid 3'5'-hydroxylase, which accepts
      flavones, flavanones, dihydroflavonols and flavonols as substrates. The
      expression of the CYP75A31 gene was found to increase in response to nitrogen
      deprivation, in accordance with other genes in the phenylpropanoid pathway, as
      expected for a gene involved in flavonoid metabolism.

PMID- 20128893
TI  - A disparity between physician attitudes and practice regarding hyperglycemia in
      pediatric intensive care units in the United States: a survey on actual practice
      habits.
AB  - INTRODUCTION: Hyperglycemia is common in critically ill patients and is
      associated with increased morbidity and mortality. Strict glycemic control
      improves outcomes in some adult populations and may have similar effects in
      children. While glycemic control has become standard care in adults, little is
      known regarding hyperglycemia management strategies used by pediatric critical
      care practitioners. We sought to assess both the beliefs and practice habits
      regarding glycemic control in pediatric intensive care units (ICUs) in the United
      States (US). METHODS: We surveyed 30 US pediatric ICUs from January to May 2009.
      Surveys were conducted by phone between the investigators and participating
      centers and consisted of a 22-point questionnaire devised to assess physician
      perceptions and center-specific management strategies regarding glycemic control.
      RESULTS: ICUs included a cross section of centers throughout the US. Fourteen out
      of 30 centers believe all critically ill hyperglycemic adults should be treated,
      while 3/30 believe all critically ill children should be treated. Twenty-nine of
      30 believe some subsets of adults with hyperglycemia should be treated, while
      20/30 believe some subsets of children should receive glycemic control. A total
      of 70%, 73%, 80%, 27%, and 40% of centers believe hyperglycemia adversely affects
      outcomes in cardiac, trauma, traumatic brain injury, general medical, and general
      surgical pediatric patients, respectively. However, only six centers use a
      standard, uniform approach to treat hyperglycemia at their institution. Sixty
      percent of centers believe hypoglycemia is more dangerous than hyperglycemia.
      Seventy percent listed fear of management-induced hypoglycemia as a barrier to
      glycemic control at their center. CONCLUSIONS: Considerable disparity exists
      between physician beliefs and actual practice habits regarding glycemic control
      among pediatric practitioners, with few centers reporting the use of any
      consistent standard approach to screening and management. Physicians wishing to
      practice glycemic control in their critically ill pediatric patients may want to
      consider adopting center-wide uniform approaches to improve safety and efficacy
      of treatment.

PMID- 20128894
TI  - A comparison of lower limb EMG and ground reaction forces between barefoot and
      shod gait in participants with diabetic neuropathic and healthy controls.
AB  - BACKGROUND: It is known that when barefoot, gait biomechanics of diabetic
      neuropathic patients differ from non-diabetic individuals. However, it is still
      unknown whether these biomechanical changes are also present during shod gait
      which is clinically advised for these patients. This study investigated the
      effect of the participants own shoes on gait biomechanics in diabetic neuropathic
      individuals compared to barefoot gait patterns and healthy controls. METHODS:
      Ground reaction forces and lower limb EMG activities were analyzed in 21 non
      diabetic adults (50.9 +/- 7.3 yr, 24.3 +/- 2.6 kg/m2) and 24 diabetic neuropathic
      participants (55.2 +/- 7.9 yr, 27.0 +/- 4.4 kg/m2). EMG patterns of vastus
      lateralis, lateral gastrocnemius and tibialis anterior, along with the vertical
      and antero-posterior ground reaction forces were studied during shod and barefoot
      gait. RESULTS: Regardless of the disease, walking with shoes promoted an increase
      in the first peak vertical force and the peak horizontal propulsive force.
      Diabetic individuals had a delay in the lateral gastrocnemius EMG activity with
      no delay in the vastus lateralis. They also demonstrated a higher peak horizontal
      braking force walking with shoes compared to barefoot. Diabetic participants also
      had a smaller second peak vertical force in shod gait and a delay in the vastus
      lateralis EMG activity in barefoot gait compared to controls. CONCLUSIONS: The
      change in plantar sensory information that occurs when wearing shoes revealed a
      different motor strategy in diabetic individuals. Walking with shoes did not
      attenuate vertical forces in either group. Though changes in motor strategy were
      apparent, the biomechanical did not support the argument that the use of shoes
      contributes to altered motor responses during gait.

PMID- 20128896
TI  - The backbone of the post-synaptic density originated in a unicellular ancestor of
      choanoflagellates and metazoans.
AB  - BACKGROUND: Comparative genomics of the early diverging metazoan lineages and of
      their unicellular sister-groups opens new window to reconstructing the genetic
      changes which preceded or accompanied the evolution of multicellular body plans.
      A recent analysis found that the genome of the nerve-less sponges encodes the
      homologues of most vertebrate post-synaptic proteins. In vertebrate excitatory
      synapses, these proteins assemble to form the post-synaptic density, a complex
      molecular platform linking membrane receptors, components of their signalling
      pathways, and the cytoskeleton. Newly available genomes from Monosiga brevicollis
      (a member of Choanoflagellata, the closest unicellular relatives of animals) and
      Trichoplax adhaerens (a member of Placozoa: besides sponges, the only nerve-less
      metazoans) offer an opportunity to refine our understanding of post-synaptic
      protein evolution. RESULTS: Searches for orthologous proteins and reconstruction
      of gene gains/losses based on the taxon phylogeny indicate that post-synaptic
      proteins originated in two main steps. The backbone scaffold proteins (Shank,
      Homer, DLG) and some of their partners were acquired in a unicellular ancestor of
      choanoflagellates and metazoans. A substantial additional set appeared in an
      exclusive ancestor of the Metazoa. The placozoan genome contains most post
      synaptic genes but lacks some of them. Notably, the master-scaffold protein Shank
      might have been lost secondarily in the placozoan lineage. CONCLUSIONS: The time
      of origination of most post-synaptic proteins was not concomitant with the
      acquisition of synapses or neural-like cells. The backbone of the scaffold
      emerged in a unicellular context and was probably not involved in cell-cell
      communication. Based on the reconstructed protein composition and potential
      interactions, its ancestral function could have been to link calcium signalling
      and cytoskeleton regulation. The complex later became integrated into the
      evolving synapse through the addition of novel functionalities.

PMID- 20128895
TI  - Candidate genes for alcohol preference identified by expression profiling in
      alcohol-preferring and -nonpreferring reciprocal congenic rats.
AB  - BACKGROUND: Selectively bred alcohol-preferring (P) and alcohol-nonpreferring
      (NP) rats differ greatly in alcohol preference, in part due to a highly
      significant quantitative trait locus (QTL) on chromosome 4. Alcohol consumption
      scores of reciprocal chromosome 4 congenic strains NP.P and P.NP correlated with
      the introgressed interval. The goal of this study was to identify candidate genes
      that may influence alcohol consumption by comparing gene expression in five brain
      regions of alcohol-naive inbred alcohol-preferring and P.NP congenic rats:
      amygdala, nucleus accumbens, hippocampus, caudate putamen, and frontal cortex.
      RESULTS: Within the QTL region, 104 cis-regulated probe sets were differentially
      expressed in more than one region, and an additional 53 were differentially
      expressed in a single region. Fewer trans-regulated probe sets were detected, and
      most differed in only one region. Analysis of the average expression values
      across the 5 brain regions yielded 141 differentially expressed cis-regulated
      probe sets and 206 trans-regulated probe sets. Comparing the present results from
      inbred alcohol-preferring vs. congenic P.NP rats to earlier results from the
      reciprocal congenic NP.P vs. inbred alcohol-nonpreferring rats demonstrated that
      74 cis-regulated probe sets were differentially expressed in the same direction
      and with a consistent magnitude of difference in at least one brain region.
      CONCLUSIONS: Cis-regulated candidate genes for alcohol consumption that lie
      within the chromosome 4 QTL were identified and confirmed by consistent results
      in two independent experiments with reciprocal congenic rats. These genes are
      strong candidates for affecting alcohol preference in the inbred alcohol
      preferring and inbred alcohol-nonpreferring rats.

PMID- 20128897
TI  - Inhibition of tomato yellow leaf curl virus (TYLCV) using whey proteins.
AB  - The antiviral activity of native and esterified whey proteins fractions (alpha
      lactalbumin, beta-lactoglobulin, and lactoferrin) was studied to inhibit tomato
      yellow leaf curl virus (TYLCV) on infected tomato plants. Whey proteins fractions
      and their esterified derivatives were sprayed into TYLCV-infected plants. Samples
      were collected from infected leaves before treatment, 7 and 15 days after
      treatment for DNA and molecular hybridization analysis. The most evident
      inhibition of virus replication was observed after 7 and 15 days using alpha
      lactoferrin and alpha-lactalbumin, respectively. Native and esterified
      lactoferrin showed complete inhibition after 7 days. On the other hand, native
      beta-lactoglobulin showed inhibition after 7 and 15 days whereas esterified beta
      lactoglobulin was comparatively more effective after 7 days. The relative amount
      of viral DNA was less affected by the esterified alpha-lactalbumin whereas native
      alpha-lactalbumin inhibited virus replication completely after 15 days. These
      results indicate that native or modified whey proteins fractions can be used for
      controlling the TYLCV-infected plants.

PMID- 20128898
TI  - Unchanged triclabendazole kinetics after co-administration with ivermectin and
      methimazole: failure of its therapeutic activity against triclabendazole
      resistant liver flukes.
AB  - BACKGROUND: The reduced drug accumulation based on enhanced drug efflux and
      metabolic capacity, identified in triclabendazole (TCBZ)-resistant Fasciola
      hepatica may contribute to the development of resistance to TCBZ. The aim of this
      work was to evaluate the pharmacokinetics and clinical efficacy of TCBZ
      administered alone or co-administered with ivermectin (IVM, efflux modulator) and
      methimazole (MTZ, metabolic inhibitor) in TCBZ-resistant F. hepatica-parasitized
      sheep. Sheep infected with TCBZ-resistant F. hepatica (Sligo isolate) were
      divided into three groups (n = 4): untreated control, TCBZ-treated (i.r. at 10
      mg/kg) and TCBZ+IVM+MTZ treated sheep (10 i.r., 0.2 s.c. and 1.5 i.m. mg/kg,
      respectively). Plasma samples were collected and analysed by HPLC. In the
      clinical efficacy study, the animals were sacrificed at 15 days post-treatment to
      evaluate the comparative efficacy against TCBZ-resistant F. hepatica. RESULTS:
      The presence of IVM and MTZ did not affect the plasma disposition kinetics of
      TCBZ metabolites after the i.r. administration of TCBZ. The AUC value of TCBZ.SO
      obtained after TCBZ administration (653.9 +/- 140.6 microgxh/ml) was similar to
      that obtained after TCBZ co-administered with IVM and MTZ (650.7 +/- 122.8
      microgxh/ml). Efficacy values of 56 and 38% were observed for TCBZ alone and for
      the combined treatment, respectively. No statistical differences (P > 0.05) were
      observed in fluke counts between treated groups and untreated control, which
      confirm the resistant status of the Sligo isolate. CONCLUSIONS: The presence of
      IVM and MTZ did not affect the disposition kinetics of TCBZ and its metabolites.
      Thus, the combined drug treatment did not reverse the poor efficacy of TCBZ
      against TCBZ-resistant F. hepatica.

PMID- 20128899
TI  - Identifying type and determinants of missing items in quality of life
      questionnaires: Application to the SF-36 French version of the 2003 Decennial
      Health Survey.
AB  - BACKGROUND: Missing items are common in quality of life (QoL) questionnaires and
      present a challenge for research in this field. The development of sound
      strategies of replacement and prevention requires accurate knowledge of their
      type and determinants. METHODS: We used the 2003 French Decennial Health Survey
      of a representative sample of the general population--including 22,620 adult
      subjects who completed the SF-36 questionnaire--to test various socio
      demographic, health status and QoL variables as potential predictors of
      missingness. We constructed logistic regression models for each SF-36 item to
      identify independent predictors and classify them according to Little and Rubin
      ("missing completely at random", "missing at random" and "missing not at
      random"). RESULTS: The type of missingness was missing at random for half of the
      items of the SF-36 and missing not at random for the others. None of the items
      were missing completely at random. Independent predictors of missingness were
      age, female sex, low scores on the SF-36 subscales and in some cases low
      educational level, occupation, nationality and poor health status. CONCLUSION:
      This study of the SF-36 shows that imputation of missing items is necessary and
      emphasizes several factors for missingness that should be considered in
      prevention strategies of missing data. Similar methodologies could be applied to
      item missingness in other QoL questionnaires.

PMID- 20128900
TI  - The mode of school transportation in pre-pubertal children does not influence the
      accrual of bone mineral or the gain in bone size--two year prospective data from
      the paediatric osteoporosis preventive (POP) study.
AB  - BACKGROUND: Walking and cycling to school are one source of regular physical
      activity. The aim of this two years observational study in pre-pubertal children
      was to evaluate if walking and cycling to school was associated with higher total
      amount of physical activity and larger gain in bone mineral content (BMC) and
      bone width than when going by car or bus. METHODS: 133 boys and 99 girls aged 7-9
      years were recruited to the Malmo Prospective Paediatric Osteoporosis Prevention
      (POP) study. BMC (g) was measured by dual X-ray absorptiometry (DXA) in total
      body, lumbar spine (L2-L4) and femoral neck (FN) at baseline and after 24 months.
      Bone width was measured in L2-L4 and FN. Skeletal changes in the 57 boys and 48
      girls who consistently walked or cycled to school were compared with the 24 boys
      and 17 girls who consistently went by bus or car. All children remained in Tanner
      stage I. Level of everyday physical activity was estimated by accelerometers worn
      for four consecutive days and questionnaires. Comparisons were made by
      independent student's t-tests between means and Fisher's exact tests. Analysis of
      covariance (ANCOVA) was used to adjust for group differences in age at baseline,
      duration of organized physical activity, annual changes in length and BMC or bone
      width if there were differences in these traits at baseline. RESULTS: After the
      adjustments, there were no differences in the annual changes in BMC or bone width
      when comparing girls or boys who walked or cycled to school with those who went
      by car or bus. Furthermore, there were no differences in the levels of everyday
      physical activity objectively measured by accelerometers and all children reached
      above the by the United Kingdom Expert Consensus Group recommended level of 60
      minutes moderate to vigorous physical activity per day. CONCLUSION: A physical
      active transportation to school for two years is in pre-pubertal children not
      associated with a higher accrual of BMC or bone width than a passive mode of
      transportation, possibly due to the fact that the everyday physical activity in
      these pre-pubertal children, independent of the mode of school transportation,
      was high.

PMID- 20128901
TI  - The impact of parental migration on health status and health behaviours among
      left behind adolescent school children in China.
AB  - BACKGROUND: One out of ten of China's population are migrants, moving from rural
      to urban areas. Many leave their families behind resulting in millions of school
      children living in their rural home towns without one or both their parents.
      Little is known about the health status of these left behind children (LBC). This
      study compares the health status and health-related behaviours of left behind
      adolescent school children and their counterparts in a rural area in Southern
      China. METHODS: A cross-sectional study was conducted among middle school
      students in Fuyang Township, Guangdong, China (2007-2008). Information about
      health behaviours, parental migration and demographic characteristics was
      collected using a self-administered questionnaire. Overweight/obesity and
      stunting were defined based on measurements of height and weight. Univariate and
      multivariate analyses were used to estimate the differences in health outcomes
      between LBC and non-LBC. RESULTS: 18.1% of the schoolchildren had one or both
      parents working away from home. Multivariate analysis showed that male LBC were
      at higher risk of skipping breakfast, higher levels of physical inactivity,
      internet addiction, having ever smoked tobacco, suicide ideation, and being
      overweight. LBC girls were more likely to drink excessive amounts of sweetened
      beverage, to watch more TV, to have ever smoked or currently smoke tobacco, to
      have ever drunk alcohol and to binge drinking. They were also more likely to be
      unhappy, to think of planning suicide and consider leaving home. CONCLUSIONS: Our
      findings suggest that parental migration is a risk factor for unhealthy
      behaviours amongst adolescent school children in rural China. Further research is
      required in addition to the consideration of the implications for policies and
      programmes to protect LBC.

PMID- 20128902
TI  - Physical and mental health-related correlates of physical function in community
      dwelling older adults: a cross sectional study.
AB  - BACKGROUND: Physical function is the ability to perform both basic and
      instrumental activities of daily living, and the ability of older adults to
      reside in the community depends to a large extent on their level of physical
      function. Multiple physical and health-related variables may differentially
      affect physical function, but they have not been well characterized. The purpose
      of this investigation was to identify and examine physical and mental health
      related correlates of physical function in a sample of community-dwelling older
      adults. METHODS: Nine hundred and four community dwelling older men (n = 263) and
      women (n = 641) with a mean (95% Confidence Interval) age of 76.6 (76.1, 77.1)
      years underwent tests of physical function (Timed Up and Go; TUG), Body Mass
      Index (BMI) was calculated from measured height and weight, and data were
      collected on self-reported health quality of life (SF-36), falls during the past
      6 months, number of medications per day, depression (Geriatric Depression Scale;
      GDS), social support, and sociodemographic variables. RESULTS: Subjects completed
      the TUG in 8.7 (8.2, 9.2) seconds and expended 6,976 (6,669, 7,284) Kcal.wk-1 in
      physical activity. The older persons had a mean BMI of 27. 6 (27.2, 28.0), 62%
      took 3 or more medications per day, and 14.4% had fallen one or more times over
      the last 6 months. Mean scores on the Mental Component Summary (MCS) was 50.6
      (50.2, 51,0) and the Physical Component Summary (PCS) was 41.3 (40.8,
      41.8).Multiple sequential regression analysis showed that, after adjustment for
      TUG floor surface correlates of physical function included age, sex, education,
      physical activity (weekly energy expenditure), general health, bodily pain,
      number of medications taken per day, depression and Body Mass Index. Further,
      there is a dose response relationship such that greater degree of physical
      function impairment is associated with poorer scores on physical health-related
      variables. CONCLUSIONS: Physical function in community-dwelling older adults is
      associated with several physical and mental health-related factors. Further study
      examining the nature of the relationships between these variables is needed.

PMID- 20128903
TI  - Consumer exposure to biocides--identification of relevant sources and evaluation
      of possible health effects.
AB  - BACKGROUND: Products containing biocides are used for a variety of purposes in
      the home environment. To assess potential health risks, data on products
      containing biocides were gathered by means of a market survey, exposures were
      estimated using a worst case scenario approach (screening), the hazard of the
      active components were evaluated, and a preliminary risk assessment was
      conducted. METHODS: Information on biocide-containing products was collected by
      on-site research, by an internet inquiry as well as research into databases and
      lists of active substances. Twenty active substances were selected for detailed
      investigation. The products containing these substances were subsequently
      classified by range of application; typical concentrations were derived.
      Potential exposures were then estimated using a worst case scenario approach
      according to the European Commission's Technical Guidance Document on Risk
      Assessment. Relevant combinations of scenarios and active substances were
      identified. The toxicological data for these substances were compiled in
      substance dossiers. For estimating risks, the margins of exposure (MOEs) were
      determined. RESULTS: Numerous consumer products were found to contain biocides.
      However, it appeared that only a limited number of biocidal active substances or
      groups of biocidal active substances were being used. The lowest MOEs for dermal
      exposure or exposure by inhalation were obtained for the following scenarios and
      biocides: indoor pest control using sprays, stickers or evaporators
      (chlorpyrifos, dichlorvos) and spraying of disinfectants as well as cleaning of
      surfaces with concentrates (hydrogen peroxide, formaldehyde, glutardialdehyde).
      The risk from aggregate exposure to individual biocides via different exposure
      scenarios was higher than the highest single exposure on average by a factor of
      three. From the 20 biocides assessed 10 had skin-sensitizing properties. The
      biocides isothiazolinone (mixture of 5-chloro-2-methyl-2H-isothiazolin-3-one and
      2-methyl-2H-isothiazolin-3-one, CMI/MI), glutardialdehyde, formaldehyde and
      chloroacetamide may be present in household products in concentrations which have
      induced sensitization in experimental studies. CONCLUSIONS: Exposure to biocides
      from household products may contribute to induction of sensitization in the
      population. The use of biocides in consumer products should be carefully
      evaluated. Detailed risk assessments will become available within the framework
      of the EU Biocides Directive.

PMID- 20128904
TI  - Effect of exogenous circulating anti-bPL antibodies on bovine placental lactogen
      measurements in foetal samples.
AB  - BACKGROUND: The involvement of placental lactogen (PL) in the regulation of
      foetal growth has been investigated in different species by in vivo
      immunomodulation techniques. However, when circulating antibodies are present
      together with the hormone, the procedure for hormonal measurement becomes
      considerably complex. The aim of this study was the immunoneutralization of
      bovine placental lactogen (bPL) concentrations in bovine foetal circulation by
      direct infusion of rabbit anti-bPL purified immunoglobulins (IgG) via a foetal
      catheter (in vivo study). The ability of a RIA based on guinea pig anti-bPL
      antiserum, for the measurement of bPL concentrations in samples containing
      exogenous rabbit anti-bPL immunoglobulins, was also analyzed in in vitro and in
      vivo conditions. METHODS: Six bovine foetuses were chronic cannulated on the
      aorta via the medial tarsal artery. Infusion of rabbit anti-bPL IgG was performed
      during late gestation. Pooled rabbit anti-bPL antisera had a maximal
      neutralization capacity of 25 microg bPL/mL of immunoglobulin. Interference of
      rabbit anti-bPL immunoglobulin with radioimmunoassay measurement using guinea pig
      anti-bPL as primary antibody was first evaluated in vitro. Polyclonal anti-bPL
      antibodies raised in rabbit were added in foetal sera to produce 100 samples with
      known antibodies titers (dilutions ranging from 1:2,500 till 1:1,280,000).
      RESULT(S): Assessment of the interference of rabbit anti-bPL antibody showed that
      bPL concentrations were significantly lower (P < 0.05) in samples added with
      dilutions of rabbit antiserum lower than 1:80,000 (one foetus) or 1:10,000 (four
      foetuses). It was also shown that the recovery of added bPL (12 ng/mL) was
      markedly reduced in those samples in which exogenous rabbit anti-bPL were added
      at dilutions lower than 1:20,000. Concentrations of foetal bPL were determined in
      samples from cannulated foetuses. In foetuses 1 and 6, bPL concentrations
      remained almost unchanged (<5 ng/mL) during the whole experimental period. In
      Foetus 3, bPL concentrations decreased immediately after IgG infusion and
      thereafter, they increased until parturition. CONCLUSION(S): The use of a bPL RIA
      using a guinea pig anti-bPL as primary antiserum allowed for the measurement of
      bPL concentrations in foetal plasma in presence of rabbit anti-bPL IgG into the
      foetal circulation. Long-term foetal catheterization allowed for the study of the
      influence of direct infusion of anti-bPL IgG on peripheral bPL concentrations in
      bovine foetuses.

PMID- 20128905
TI  - A review of ureteral injuries after external trauma.
AB  - INTRODUCTION: Ureteral trauma is rare, accounting for less than 1% of all
      urologic traumas. However, a missed ureteral injury can result in significant
      morbidity and mortality. The purpose of this article is to review the literature
      since 1961 with the primary objective to present the largest medical literature
      review, to date, regarding ureteral trauma. Several anatomic and physiologic
      considerations are paramount regarding ureteral injuries management. LITERATURE
      REVIEW: Eighty-one articles pertaining to traumatic ureteral injuries were
      reviewed. Data from these studies were compiled and analyzed. The majority of the
      study population was young males. The proximal ureter was the most frequently
      injured portion. Associated injuries were present in 90.4% of patients. Admission
      urinalysis demonstrated hematuria in only 44.4% patients. Intravenous ureterogram
      (IVU) failed to diagnose ureteral injuries either upon admission or in the
      operating room in 42.8% of cases. Ureteroureterostomy, with or without indwelling
      stent, was the surgical procedure of choice for both trauma surgeons and
      urologists (59%). Complications occurred in 36.2% of cases. The mortality rate
      was 17%. CONCLUSION: The mechanism for ureteral injuries in adults is more
      commonly penetrating than blunt. The upper third of the ureter is more often
      injured than the middle and lower thirds. Associated injuries are frequently
      present. CT scan and retrograde pyelography accurately identify ureteral injuries
      when performed together. Ureteroureterostomy, with or without indwelling stent,
      is the surgical procedure of choice of both trauma surgeons and urologists alike.
      Delay in diagnosis is correlated with a poor prognosis.

PMID- 20128906
TI  - Heterologous expression of leader-less pga gene in Pichia pastoris: intracellular
      production of prokaryotic enzyme.
AB  - BACKGROUND: Penicillin G acylase of Escherichia coli (PGAEc) is a commercially
      valuable enzyme for which efficient bacterial expression systems have been
      developed. The enzyme is used as a catalyst for the hydrolytic production of beta
      lactam nuclei or for the synthesis of semi-synthetic penicillins such as
      ampicillin, amoxicillin and cephalexin. To become a mature, periplasmic enzyme,
      the inactive prepropeptide of PGA has to undergo complex processing that begins
      in the cytoplasm (autocatalytic cleavage), continues at crossing the cytoplasmic
      membrane (signal sequence removing), and it is completed in the periplasm. Since
      there are reports on impressive cytosolic expression of bacterial proteins in
      Pichia, we have cloned the leader-less gene encoding PGAEc in this host and
      studied yeast production capacity and enzyme authenticity. RESULTS: Leader-less
      pga gene encoding PGAEcunder the control of AOX1 promoter was cloned in Pichia
      pastoris X-33. The intracellular overproduction of heterologous PGAEc(hPGAEc) was
      evaluated in a stirred 10 litre bioreactor in high-cell density, fed batch
      cultures using different profiles of transient phases. Under optimal conditions,
      the average volumetric activity of 25900 U l-1 was reached. The hPGAEc was
      purified, characterized and compared with the wild-type PGAEc. The alpha-subunit
      of the hPGAEc formed in the cytosol was processed aberrantly resulting in two
      forms with C- terminuses extended to the spacer peptide. The enzyme exhibited
      modified traits: the activity of the purified enzyme was reduced to 49%, the
      ratios of hydrolytic activities with cephalexin, phenylacetamide or 6-nitro-3
      phenylacetylamidobenzoic acid (NIPAB) to penicillin G increased and the enzyme
      showed a better synthesis/hydrolysis ratio for the synthesis of cephalexin.
      CONCLUSIONS: Presented results provide useful data regarding fermentation
      strategy, intracellular biosynthetic potential, and consequences of the
      heterologous expression of PGAEc in P. pastoris X-33. Aberrant processing of the
      precursor of PGAEc in the cytosol yielded the mature enzyme with modified traits.

PMID- 20128907
TI  - Primary prevention from the epidemiology perspective: three examples from the
      practice.
AB  - BACKGROUND: Primary prevention programmes are of increasing importance to reduce
      the impact of chronic diseases on the individual, institutional and societal
      level. However, most initiatives that develop and implement primary prevention
      programmes are not evaluated with scientific rigor. On the basis of three
      different projects we discuss necessary steps on the road to evidence-based
      primary prevention. DISCUSSION: We first discuss how to identify suitable target
      groups exploiting sophisticated statistical methods. This is illustrated using
      data from a health survey conducted in a federal state of Germany. A literature
      review is the more typical approach to identify target groups that is
      demonstrated using a European project on the prevention of childhood obesity. In
      the next step, modifiable risk factors and realistic targets of the intervention
      have to be specified. These determine the outcome measures that in turn are used
      for effect evaluation. Both, the target groups and the outcome measures, lay the
      ground for the study design and the definition of comparison groups as can be
      seen in our European project. This project also illustrates the development and
      implementation of a prevention programme. These may require active involvement of
      participants which can be achieved by participatory approaches taking into
      account the socio-cultural and living environment. Evaluation is of utmost
      importance for any intervention to assess structure, process and outcome
      according to rigid scientific criteria. Different approaches used for this are
      discussed and illustrated by a methodological project developed within a health
      promotion programme in a deprived area. Eventually the challenge of transferring
      an evidence-based intervention into practice and to achieve its sustainability is
      addressed. SUMMARY: This article describes a general roadmap to primary
      prevention comprising (1) the identification of target groups and settings, (2)
      the identification of modifiable risk factors and endpoints, (3) the development
      and implementation of an intervention programme, (4) the evaluation of structure,
      process and outcome and (5) the transfer of an evidence-based intervention into
      practice.

PMID- 20128909
TI  - Genomic and small RNA sequencing of Miscanthus x giganteus shows the utility of
      sorghum as a reference genome sequence for Andropogoneae grasses.
AB  - BACKGROUND: Miscanthus x giganteus (Mxg) is a perennial grass that produces
      superior biomass yields in temperate environments. The essentially
      uncharacterized triploid genome (3n = 57, x = 19) of Mxg is likely critical for
      the rapid growth of this vegetatively propagated interspecific hybrid. RESULTS: A
      survey of the complex Mxg genome was conducted using 454 pyrosequencing of
      genomic DNA and Illumina sequencing-by-synthesis of small RNA. We found that the
      coding fraction of the Mxg genome has a high level of sequence identity to that
      of other grasses. Highly repetitive sequences representing the great majority of
      the Mxg genome were predicted using non-cognate assembly for de novo repeat
      detection. Twelve abundant families of repeat were observed, with those related
      to either transposons or centromeric repeats likely to comprise over 95% of the
      genome. Comparisons of abundant repeat sequences to a small RNA survey of three
      Mxg organs (leaf, rhizome, inflorescence) revealed that the majority of observed
      24-nucleotide small RNAs are derived from these repetitive sequences. We show
      that high-copy-number repeats match more of the small RNA, even when the amount
      of the repeat sequence in the genome is accounted for. CONCLUSIONS: We show that
      major repeats are present within the triploid Mxg genome and are actively
      producing small RNAs. We also confirm the hypothesized origins of Mxg, and
      suggest that while the repeat content of Mxg differs from sorghum, the sorghum
      genome is likely to be of utility in the assembly of a gene-space sequence of
      Mxg.

PMID- 20128910
TI  - Inferring the functions of longevity genes with modular subnetwork biomarkers of
      Caenorhabditis elegans aging.
AB  - A central goal of biogerontology is to identify robust gene-expression biomarkers
      of aging. Here we develop a method where the biomarkers are networks of genes
      selected based on age-dependent activity and a graph-theoretic property called
      modularity. Tested on Caenorhabditis elegans, our algorithm yields better
      biomarkers than previous methods - they are more conserved across studies and
      better predictors of age. We apply these modular biomarkers to assign novel aging
      related functions to poorly characterized longevity genes.

PMID- 20128911
TI  - SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts.
AB  - BACKGROUND: Lymphoid Enhancer Factor-1 (Lef-1) is a member of a transcription
      factor family that acts as downstream mediator of the Wnt/beta-catenin signalling
      pathway which plays a critical role in osteoblast proliferation and
      differentiation. In a search for Lef-1 responsive genes in human osteoblasts, we
      focused on the transcriptional regulation of the SLUG, a zinc finger
      transcription factor belonging to the Snail family of developmental proteins.
      Although the role of SLUG in epithelial-mesenchymal transition and cell motility
      during embryogenesis is well documented, the functions of this factor in most
      normal adult human tissues are largely unknown. In this study we investigated
      SLUG expression in normal human osteoblasts and their mesenchymal precursors, and
      its possible correlation with Lef-1 and Wnt/beta-catenin signalling. RESULTS: The
      experiments were performed on normal human primary osteoblasts obtained from bone
      fragments, cultured in osteogenic conditions in presence of Lef-1 expression
      vector or GSK-3beta inhibitor, SB216763. We demonstrated that the transcription
      factor SLUG is present in osteoblasts as well as in their mesenchymal precursors
      obtained from Wharton's Jelly of human umbilical cord and induced to osteoblastic
      differentiation. We found that SLUG is positively correlated with RUNX2
      expression and deposition of mineralized matrix, and is regulated by Lef-1 and
      beta-catenin. Consistently, Chromatin Immunoprecipitation (ChIP) assay, used to
      detect the direct Lef/Tcf factors that are responsible for the promoter activity
      of SLUG gene, demonstrated that Lef-1, TCF-1 and TCF4 are recruited to the SLUG
      gene promoter "in vivo". CONCLUSION: These studies provide, for the first time,
      the evidence that SLUG expression is correlated with osteogenic commitment, and
      is positively regulated by Lef-1 signal in normal human osteoblasts. These
      findings will help to further understand the regulation of the human SLUG gene
      and reveal the biological functions of SLUG in the context of bone tissue.

PMID- 20128908
TI  - Role of platelets in neuroinflammation: a wide-angle perspective.
AB  - OBJECTIVES: This review summarizes recent developments in platelet biology
      relevant to neuroinflammatory disorders. Multiple sclerosis (MS) is taken as the
      "Poster Child" of these disorders but the implications are wide. The role of
      platelets in inflammation is well appreciated in the cardiovascular and cancer
      research communities but appears to be relatively neglected in neurological
      research. ORGANIZATION: After a brief introduction to platelets, topics covered
      include the matrix metalloproteinases, platelet chemokines, cytokines and growth
      factors, the recent finding of platelet PPAR receptors and Toll-like receptors,
      complement, bioactive lipids, and other agents/functions likely to be relevant in
      neuroinflammatory diseases. Each section cites literature linking the topic to
      areas of active research in MS or other disorders, including especially
      Alzheimer's disease. CONCLUSION: The final section summarizes evidence of
      platelet involvement in MS. The general conclusion is that platelets may be key
      players in MS and related disorders, and warrant more attention in neurological
      research.

PMID- 20128912
TI  - Endometrial cancer in Puerto Rico: incidence, mortality and survival (1992-2003).
AB  - BACKGROUND: Endometrial cancer is the most common gynecologic malignancy in
      Puerto Rico and the United States (US). METHODS: We compare the age-specific and
      age-adjusted incidence and mortality rates and the survival of endometrial cancer
      in Puerto Rico with that of non-Hispanic whites (NHW), non-Hispanic blacks (NHB)
      and Hispanics in the US. Data from the Puerto Rico Central Cancer Registry and
      the Surveillance, Epidemiology, and End Results program were analyzed from 1992
      2003. RESULTS: Age-standardized incidence rates of endometrial cancer increased
      significantly (p < 0.05) in Puerto Rico (APC = 2.8%) and among NHB (APC = 1.9%)
      and remained constant (p > 0.05) for NHW (APC = -0.1%) and Hispanics in the US
      (APC = 0.4%). Mortality trends remained constant in all racial/ethnic groups (p >
      0.05). For 1999-2003, women in Puerto Rico had similar incidence of endometrial
      cancer as Hispanics (Standardized rate ratio [SRR] = 0.94, 95% CI = 0.87-1.01),
      although their risk was lower than that of NHW (SRR = 0.56, 95% CI = 0.53-0.59)
      and NHB (SRR = 0.91, 95% CI = 0.84-0.98). Meanwhile, women in Puerto Rico had 15%
      higher risk of death than Hispanic women (SRR = 1.15, 95% CI = 1.03-1.30) similar
      risk than NHW (SRR = 0.93, 95% CI = 0.83-1.03), and lower risk than NHB (SRR =
      0.51, 95% CI = 0.46-0.57). Puerto Rico (63.1%) and NHB (56.8%) had a lower 5-year
      survival than NHW (78.4%) and Hispanics (79.5%). An age-adjusted Cox proportional
      hazards model showed that compared with women in Puerto Rico, Hispanic women in
      the United States had 37% lower mortality risk (HR = 0.63, 95% CI = 0.56-0.71)
      and NHW had 53% lower mortality risk (HR = 0.47, 95% CI = 0.43-0.52) after 5
      years of diagnosis; NHB women had 22% higher mortality risk than women in Puerto
      Rico (HR = 1.22, 95% CI = 1.09-1.36). CONCLUSIONS: The lower burden of
      endometrial cancer in Puerto Rico suggests the presence of protective factors or
      lower exposure to risk factors in this population, although increases in
      incidence suggest changes in the occurrence of lifestyles and environmental risk
      factors. Meanwhile, the lower five-year survival from endometrial cancer among
      Puerto Ricans suggests a health disparity for this group in areas such as quality
      of care and/or differences in terms of stage at diagnosis and associated
      comorbidities. Assessment of disease risk factors and characteristics, and access
      and response to treatment is required to further understand these results.

PMID- 20128913
TI  - Self-reported physical and mental health status and quality of life in
      adolescents: a latent variable mediation model.
AB  - BACKGROUND: We examined adolescents' differentiation of their self-reported
      physical and mental health status, the relative importance of these variables and
      five important life domains (satisfaction with family, friends, living
      environment, school and self) with respect to adolescents' global quality of life
      (QOL), and the extent to which the five life domains mediate the relationships
      between self-reported physical and mental health status and global QOL. METHODS:
      The data were obtained via a cross-sectional health survey of 8,225 adolescents
      in 49 schools in British Columbia, Canada. Structural equation modeling was
      applied to test the implied latent variable mediation model. The Pratt index (d)
      was used to evaluate variable importance. RESULTS: Relative to one another, self
      reported mental health status was found to be more strongly associated with
      depressive symptoms, and self-reported physical health status more strongly
      associated with physical activity. Self-reported physical and mental health
      status and the five life domains explained 76% of the variance in global QOL.
      Relatively poorer mental health and physical health were significantly associated
      with lower satisfaction in each of the life domains. Global QOL was predominantly
      explained by three of the variables: mental health status (d = 30%), satisfaction
      with self (d = 42%), and satisfaction with family (d = 20%). Satisfaction with
      self and family were the predominant mediators of mental health and global QOL
      (45% total mediation), and of physical health and global QOL (68% total
      mediation). CONCLUSIONS: This study provides support for the validity and
      relevance of differentiating self-reported physical and mental health status in
      adolescent health surveys. Self-reported mental health status and, to a lesser
      extent, self-reported physical health status were associated with significant
      differences in the adolescents' satisfaction with their family, friends, living
      environment, school experiences, self, and their global QOL. Questions about
      adolescents' self-reported physical and mental health status and their
      experiences with these life domains require more research attention so as to
      target appropriate supportive services, particularly for adolescents with mental
      or physical health challenges.

PMID- 20128914
TI  - Susceptibility of turkeys to pandemic-H1N1 virus by reproductive tract
      insemination.
AB  - The current pandemic influenza A H1N1 2009 (pH1N1) was first recognized in humans
      with acute respiratory diseases in April 2009 in Mexico, in swine in Canada in
      June, 2009 with respiratory disease, and in turkeys in Chile in June 2009 with a
      severe drop in egg production. Several experimental studies attempted to
      reproduce the disease in turkeys, but failed to produce respiratory infection in
      turkeys using standard inoculation routes. We demonstrated that pH1N1 virus can
      infect the reproductive tract of turkey hens after experimental intrauterine
      inoculation, causing decreased egg production. This route of exposure is
      realistic in modern turkey production because turkey hens are handled once a week
      for intrauterine insemination in order to produce fertile eggs. This
      understanding of virus exposure provides an improved understanding of the
      pathogenesis of the disease and can improve poultry husbandry to prevent disease
      outbreaks.

PMID- 20128915
TI  - Periplasmic expression of soluble single chain T cell receptors is rescued by the
      chaperone FkpA.
AB  - BACKGROUND: Efficient expression systems exist for antibody (Ab) molecules, which
      allow for characterization of large numbers of individual Ab variants. In
      contrast, such expression systems have been lacking for soluble T cell receptors
      (TCRs). Attempts to generate bacterial systems have generally resulted in low
      yields and material which is prone to aggregation and proteolysis. Here we
      present an optimized periplasmic bacterial expression system for soluble single
      chain (sc) TCRs. RESULTS: The effect of 1) over-expression of the periplasmic
      chaperon FkpA, 2) culture conditions and 3) molecular design was investigated.
      Elevated levels of FkpA allowed periplasmic soluble scTCR expression, presumably
      by preventing premature aggregation and inclusion body formation. Periplasmic
      expression enables disulphide bond formation, which is a prerequisite for the
      scTCR to reach its correct fold. It also enables quick and easy recovery of
      correctly folded protein without the need for time-consuming downstream
      processing. Expression without IPTG induction further improved the periplasmic
      expression yield, while addition of sucrose to the growth medium showed little
      effect. Shaker flask yield of mg levels of active purified material was obtained.
      The Valphabeta domain orientation was far superior to the Vbetaalpha domain
      orientation regarding monomeric yield of functionally folded molecules.
      CONCLUSION: The general expression regime presented here allows for rapid
      production of soluble scTCRs and is applicable for 1) high yield recovery
      sufficient for biophysical characterization and 2) high throughput screening of
      such molecules following molecular engineering.

PMID- 20128916
TI  - Bias correction and Bayesian analysis of aggregate counts in SAGE libraries.
AB  - BACKGROUND: Tag-based techniques, such as SAGE, are commonly used to sample the
      mRNA pool of an organism's transcriptome. Incomplete digestion during the tag
      formation process may allow for multiple tags to be generated from a given mRNA
      transcript. The probability of forming a tag varies with its relative location.
      As a result, the observed tag counts represent a biased sample of the actual
      transcript pool. In SAGE this bias can be avoided by ignoring all but the 3' most
      tag but will discard a large fraction of the observed data. Taking this bias into
      account should allow more of the available data to be used leading to increased
      statistical power. RESULTS: Three new hierarchical models, which directly embed a
      model for the variation in tag formation probability, are proposed and their
      associated Bayesian inference algorithms are developed. These models may be
      applied to libraries at both the tag and aggregate level. Simulation experiments
      and analysis of real data are used to contrast the accuracy of the various
      methods. The consequences of tag formation bias are discussed in the context of
      testing differential expression. A description is given as to how these
      algorithms can be applied in that context. CONCLUSIONS: Several Bayesian
      inference algorithms that account for tag formation effects are compared with the
      DPB algorithm providing clear evidence of superior performance. The accuracy of
      inferences when using a particular non-informative prior is found to depend on
      the expression level of a given gene. The multivariate nature of the approach
      easily allows both univariate and joint tests of differential expression.
      Calculations demonstrate the potential for false positive and negative findings
      due to variation in tag formation probabilities across samples when testing for
      differential expression.

PMID- 20128917
TI  - Prevalence of Helicobacter pylori infection among new outpatients with dyspepsia
      in Kuwait.
AB  - BACKGROUND: Testing and treatment for Helicobacter pylori has become widely
      accepted as the approach of choice for patients with chronic dyspepsia but no
      alarming features. We evaluated H. pylori status among outpatients with
      uninvestigated dyspepsia in Kuwait. METHODS: A prospectively collected database
      for 1035 patients who had undergone 13C-urea breath tests (UBT) for various
      indications was reviewed for the period from October 2007 to July 2009. The
      status of H. pylori in dyspeptic patients was determined by UBT. RESULTS: Among
      the 362 patients who had undergone UBT for uninvestigated dyspepsia, 49.7% were
      positive for H. pylori (95% CI = 44%-55%) and the percentage increased with age
      (35.8% at 20-29 years, 95% CI = 25.4% - 47.2%; 59.3% at 30-39 years, 95% CI =
      48.5% - 69.5%) (P = 0.013). The prevalence of H. pylori was 42.6% among Kuwaitis
      (95% CI = 35%-50%) and 57.6% (95% CI = 49.8%-65%) among expatriates (p = 0.004).
      The prevalence among males was 51.3%, while in females it was 48.6%. CONCLUSIONS:
      Almost half of the patients with dyspeptic symptoms in Kuwait were positive for
      H. pylori, though the prevalence varied with age and was higher among
      expatriates. The American Gastroenterology Association guidelines recommending
      testing and treatment for H. pylori for patients with uninvestigated dyspepsia
      should be endorsed in Kuwait.

PMID- 20128918
TI  - BABAR: an R package to simplify the normalisation of common reference design
      microarray-based transcriptomic datasets.
AB  - BACKGROUND: The development of DNA microarrays has facilitated the generation of
      hundreds of thousands of transcriptomic datasets. The use of a common reference
      microarray design allows existing transcriptomic data to be readily compared and
      re-analysed in the light of new data, and the combination of this design with
      large datasets is ideal for 'systems'-level analyses. One issue is that these
      datasets are typically collected over many years and may be heterogeneous in
      nature, containing different microarray file formats and gene array layouts, dye
      swaps, and showing varying scales of log2- ratios of expression between
      microarrays. Excellent software exists for the normalisation and analysis of
      microarray data but many data have yet to be analysed as existing methods
      struggle with heterogeneous datasets; options include normalising microarrays on
      an individual or experimental group basis. Our solution was to develop the Batch
      Anti-Banana Algorithm in R (BABAR) algorithm and software package which uses
      cyclic loess to normalise across the complete dataset. We have already used BABAR
      to analyse the function of Salmonella genes involved in the process of infection
      of mammalian cells. RESULTS: The only input required by BABAR is unprocessed
      GenePix or BlueFuse microarray data files. BABAR provides a combination of
      'within' and 'between' microarray normalisation steps and diagnostic boxplots.
      When applied to a real heterogeneous dataset, BABAR normalised the dataset to
      produce a comparable scaling between the microarrays, with the microarray data in
      excellent agreement with RT-PCR analysis. When applied to a real non
      heterogeneous dataset and a simulated dataset, BABAR's performance in identifying
      differentially expressed genes showed some benefits over standard techniques.
      CONCLUSIONS: BABAR is an easy-to-use software tool, simplifying the simultaneous
      normalisation of heterogeneous two-colour common reference design cDNA microarray
      based transcriptomic datasets. We show BABAR transforms real and simulated
      datasets to allow for the correct interpretation of these data, and is the ideal
      tool to facilitate the identification of differentially expressed genes or
      network inference analysis from transcriptomic datasets.

PMID- 20128919
TI  - Loratadine dysregulates cell cycle progression and enhances the effect of
      radiation in human tumor cell lines.
AB  - BACKGROUND: The histamine receptor-1 (H1)-antagonist, loratadine has been shown
      to inhibit growth of human colon cancer xenografts in part due to cell cycle
      arrest in G2/M. Since this is a radiation sensitive phase of the cell cycle, we
      sought to determine if loratadine modifies radiosensitivity in several human
      tumor cell lines with emphasis on human colon carcinoma (HT29). METHODS: Cells
      were treated with several doses of loratadine at several time points before and
      after exposure to radiation. Radiation dose modifying factors (DMF) were
      determined using full radiation dose response survival curves. Cell cycle phase
      was determined by flow cytometry and the expression of the cell cycle-associated
      proteins Chk1, pChk1(ser345), and Cyclin B was analyzed by western blot. RESULTS:
      Loratadine pre-treatment of exponentially growing cells (75 microM, 24 hours)
      increased radiation-induced cytotoxicity yielding a radiation DMF of 1.95.
      However, treatment of plateau phase cells also yielded a DMF of 1.3 suggesting
      that mechanisms other than cell cycle arrest also contribute to loratadine
      mediated radiation modification. Like irradiation, loratadine initially induced
      G2/M arrest and activation of the cell-cycle associated protein Chk1 to
      pChk1(ser345), however a subsequent decrease in expression of total Chk1 and
      Cyclin B correlated with abrogation of the G2/M checkpoint. Analysis of DNA
      repair enzyme expression and DNA fragmentation revealed a distinct pattern of DNA
      damage in loratadine-treated cells in addition to enhanced radiation-induced
      damage. Taken together, these data suggest that the observed effects of
      loratadine are multifactorial in that loratadine 1) directly damages DNA, 2)
      activates Chk1 thereby promoting G2/M arrest making cells more susceptible to
      radiation-induced DNA damage and, 3) downregulates total Chk1 and Cyclin B
      abrogating the radiation-induced G2/M checkpoint and allowing cells to re-enter
      the cell cycle despite the persistence of damaged DNA. CONCLUSIONS: Given this
      unique possible mechanism of action, loratadine has potential as a
      chemotherapeutic agent and as a modifier of radiation responsiveness in the
      treatment of cancer and, as such, may warrant further clinical evaluation.

PMID- 20128920
TI  - Emotional, behavioural problems and cigarette smoking in adolescence: findings of
      a Greek cross-sectional study.
AB  - BACKGROUND: Although several studies have reported findings concerning the
      association between smoking and emotional/behavioural problems, little research
      has investigated this association after controlling for confounding factors which
      have been found to be significantly correlated with both cigarette smoking and
      emotional/behavioural problems and may have a strong effect on the relationship
      between adolescents' mental health and smoking. The present study attempted to
      assess the association between adolescents' smoking status and their
      emotional/behavioural problems after controlling for a number of possible
      confounders (i.e. age, gender, parental smoking status, exposure to family
      smoking, family socioeconomic status, adolescents' leisure time) in a Greek
      nation-wide school-based sample. METHODS: Participants completed a questionnaire
      which retrieved information about age, gender, family socioeconomic status,
      smoking status, parental smoking, adolescents' leisure time and
      emotional/behavioural problems. Data were modelled using multiple logistic
      regression analysis with adolescents' smoking status as the dependent variable.
      RESULTS: A total of 1194 (i.e. 63% response rate) of self-reported questionnaires
      (40.1% boys, 59.9% girls; 12-18 years old) were returned. Data from 1030
      participants with full data were analyzed. Cigarette smoking was strongly
      associated with higher levels of emotional/behavioural problems (p < 0.001) and
      the association was not moderated (OR = 1.13, 95% CI: 1.08-1.18) after
      controlling for the effects of other covariates. Emotional symptoms, conduct
      problems and hyperactivity/inattention were all significantly associated with
      adolescents' current smoking. CONCLUSIONS: This study supports the association
      between smoking and emotional/behavioural problems among adolescents. Addressing
      adolescents' needs regarding their emotional/behavioural health could be helpful
      in the development of effective anti-smoking strategies in school environment and
      elsewhere.

PMID- 20128921
TI  - Determinants of compliance with malaria chemoprophylaxis among French soldiers
      during missions in inter-tropical Africa.
AB  - BACKGROUND: The effectiveness of malaria chemoprophylaxis is limited by the lack
      of compliance whose determinants are not well known. METHODS: The compliance with
      malaria chemoprophylaxis has been estimated and analysed by validated
      questionnaires administered before and after the short-term missions (about four
      months) in five tropical African countries of 2,093 French soldiers from 19
      military companies involved in a prospective cohort study. "Correct compliance"
      was defined as "no missed doses" of daily drug intake during the entire mission
      and was analysed using multiple mixed-effect logistic regression model. RESULTS:
      The averaged prevalence rate of correct compliance was 46.2%, ranging from 9.6%to
      76.6% according to the companies. Incorrect compliance was significantly
      associated with eveningness (p = 0.028), a medical history of clinical malaria (p
      < 0.001) and a perceived mosquito attractiveness inferior or superior to the
      others (p < 0.007). Correct compliance was significantly associated with the
      systematic use of protective measures against mosquito bites (p < 0.001), the
      type of military operations (combat vs. training activities, p < 0.001) and other
      individual factors (p < 0.05). CONCLUSIONS: The identification of circumstances
      and profiles of persons at higher risk of lack of compliance would pave the way
      to specifically targeted strategies aimed to improve compliance with malaria
      chemoprophylaxis and, therefore, its effectiveness.

PMID- 20128922
TI  - Using the social entrepreneurship approach to generate innovative and sustainable
      malaria diagnosis interventions in Tanzania: a case study.
AB  - BACKGROUND: There have been a number of interventions to date aimed at improving
      malaria diagnostic accuracy in sub-Saharan Africa. Yet, limited success is often
      reported for a number of reasons, especially in rural settings. This paper seeks
      to provide a framework for applied research aimed to improve malaria diagnosis
      using a combination of the established methods, participatory action research and
      social entrepreneurship. METHODS: This case study introduces the idea of using
      the social entrepreneurship approach (SEA) to create innovative and sustainable
      applied health research outcomes. The following key elements define the SEA: (1)
      identifying a locally relevant research topic and plan, (2) recognizing the
      importance of international multi-disciplinary teams and the incorporation of
      local knowledge, (3) engaging in a process of continuous innovation, adaptation
      and learning, (4) remaining motivated and determined to achieve sustainable long
      term research outcomes and, (5) sharing and transferring ownership of the project
      with the international and local partner. EVALUATION: The SEA approach has a
      strong emphasis on innovation lead by local stakeholders. In this case,
      innovation resulted in a unique holistic research program aimed at understanding
      patient, laboratory and physician influences on accurate diagnosis of malaria. An
      evaluation of milestones for each SEA element revealed that the success of one
      element is intricately related to the success of other elements. CONCLUSIONS: The
      SEA will provide an additional framework for researchers and local stakeholders
      that promotes innovation and adaptability. This approach will facilitate the
      development of new ideas, strategies and approaches to understand how health
      issues, such as malaria, affect vulnerable communities.

PMID- 20128923
TI  - Whole-genome sequencing of a laboratory-evolved yeast strain.
AB  - BACKGROUND: Experimental evolution of microbial populations provides a unique
      opportunity to study evolutionary adaptation in response to controlled selective
      pressures. However, until recently it has been difficult to identify the precise
      genetic changes underlying adaptation at a genome-wide scale. New DNA sequencing
      technologies now allow the genome of parental and evolved strains of
      microorganisms to be rapidly determined. RESULTS: We sequenced >93.5% of the
      genome of a laboratory-evolved strain of the yeast Saccharomyces cerevisiae and
      its ancestor at >28x depth. Both single nucleotide polymorphisms and copy number
      amplifications were found, with specific gains over array-based methodologies
      previously used to analyze these genomes. Applying a segmentation algorithm to
      quantify structural changes, we determined the approximate genomic boundaries of
      a 5x gene amplification. These boundaries guided the recovery of breakpoint
      sequences, which provide insights into the nature of a complex genomic
      rearrangement. CONCLUSIONS: This study suggests that whole-genome sequencing can
      provide a rapid approach to uncover the genetic basis of evolutionary
      adaptations, with further applications in the study of laboratory selections and
      mutagenesis screens. In addition, we show how single-end, short read sequencing
      data can provide detailed information about structural rearrangements, and
      generate predictions about the genomic features and processes that underlie
      genome plasticity.

PMID- 20128924
TI  - Caldesmon regulates the motility of vascular smooth muscle cells by modulating
      the actin cytoskeleton stability.
AB  - BACKGROUND: Migration of vascular smooth muscle cells (SMCs) from the media to
      intima constitutes a critical step in the development of proliferative vascular
      diseases. To elucidate the regulatory mechanism of vacular SMC motility, the
      roles of caldesmon (CaD) and its phosphorylation were investigated. METHODS: We
      have performed Transwell migration assays, immunofluorescence microscopy,
      traction microscopy and cell rounding assays using A7r5 cells transfected with
      EGFP (control), EGFP-wtCaD or phosphomimetic CaD mutants, including EGFP-A1A2
      (the two PAK sites Ser452 and Ser482 converted to Ala), EGFP-A3A4 (the two Erk
      sites Ser497 and Ser527 converted to Ala), EGFP-A1234 (both PAK- and Erk-sites
      converted to Ala) and EGFP-D1234 (both PAK- and Erk-sites converted to Asp).
      RESULTS: We found that cells transfected with wtCaD, A1A2 or A3A4 mutants of CaD
      migrated at a rate approximately 50% more slowly than those EGFP-transfected
      cells. The migration activity for A1234 cells was only about 13% of control
      cells. Thus it seems both MAPK and PAK contribute to the motility of A7r5 cells
      and the effects are comparable and additive. The A1234 mutant also gave rise to
      highest strain energy and lowest rate of cell rounding. The migratory and
      contractile properties of these cells are consistent with stabilized actin
      cytoskeletal structures. Indeed, the A1234 mutant cells exhibited most robust
      stress fibers, whereas cells transfected with wtCaD or A3A4 (and A1A2) had
      moderately reinforced actin cytoskeleton. The control cells (transfected with
      EGFP alone) exhibited actin cytoskeleton that was similar to that in
      untransfected cells, and also migrated at about the same speed as the
      untransfected cells. CONCLUSIONS: These results suggest that both the expression
      level and the level of MAPK- and/or PAK-mediated phosphorylation of CaD play key
      roles in regulating the cell motility by modulating the actin cytoskeleton
      stability in dedifferentiated vascular SMCs such as A7r5.

PMID- 20128925
TI  - Retrospective French nationwide survey of childhood aggressive vascular anomalies
      of bone, 1988-2009.
AB  - OBJECTIVE: To document the epidemiological, clinical, histological and
      radiological characteristics of aggressive vascular abnormalities of bone in
      children. STUDY DESIGN: Correspondents of the French Society of Childhood
      Malignancies were asked to notify all cases of aggressive vascular abnormalities
      of bone diagnosed between January 1988 and September 2009. RESULTS: 21 cases were
      identified; 62% of the patients were boys. No familial cases were observed, and
      the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8
      16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting
      signs were bone fracture (n = 4) and respiratory distress (n = 7), but more
      indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies
      and pleural effusion, was the most frequent form of extraosseous involvement
      (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as
      potentially curative treatments. High-dose radiotherapy appeared to be effective
      on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs
      like alpha interferon and zoledrenate have had a limited impact on the course of
      pulmonary complications. The impact of bisphosphonates and alpha interferon on
      bone lesions was also difficult to assess, owing to insufficient follow-up in
      most cases, but it was occasionally positive. Six deaths were observed and the
      overall 10-year mortality rate was about 30%. The prognosis depended mainly on
      pulmonary and spinal complications. CONCLUSION: Aggressive vascular abnormalities
      of bone are extremely rare in childhood but are lifethreatening. The impact of
      anti-angiogenic drugs on pulmonary complications seems to be limited, but they
      may improve bone lesions.

PMID- 20128926
TI  - An evolved ribosome-inactivating protein targets and kills human melanoma cells
      in vitro and in vivo.
AB  - BACKGROUND: Few treatment options exist for patients with metastatic melanoma,
      resulting in poor prognosis. One standard treatment, dacarbazine (DTIC), shows
      low response rates ranging from 15 to 25 percent with an 8-month median survival
      time. The development of targeted therapeutics with novel mechanisms of action
      may improve patient outcome. Ribosome-inactivating proteins (RIPs) such as Shiga
      like Toxin 1 (SLT-1) represent powerful scaffolds for developing selective
      anticancer agents. Here we report the discovery and properties of a single chain
      ribosome-inactivating protein (scRIP) derived from the cytotoxic A subunit of SLT
      1 (SLT-1A), harboring the 7-amino acid peptide insertion IYSNKLM (termed SLT-1A
      IYSNKLM) allowing the toxin variant to selectively target and kill human melanoma
      cells. RESULTS: SLT-1A IYSNKLM was able to kill 7 of 8 human melanoma cell lines.
      This scRIP binds to 518-A2 human melanoma cells with a dissociation constant of
      18 nM, resulting in the blockage of protein synthesis and apoptosis in such
      cells. Biodistribution and imaging studies of radiolabeled SLT-1A IYSNKLM
      administered intravenously into SCID mice bearing a human melanoma xenograft
      indicate that SLT-1AI YSNKLM readily accumulates at the tumor site as opposed to
      non-target tissues. Furthermore, the co-administration of SLT-1A IYSNKLM with
      DTIC resulted in tumor regression and greatly increased survival in this mouse
      xenograft model in comparison to DTIC or SLT-1A IYSNKLM treatment alone (115 day
      median survival versus 46 and 47 days respectively; P values < 0.001). SLT-1A
      IYSNKLM is stable in serum and its intravenous administration resulted in modest
      immune responses following repeated injections in CD1 mice. CONCLUSIONS: These
      results demonstrate that the evolution of a scRIP template can lead to the
      discovery of novel cancer cell-targeted compounds and in the case of SLT-1A
      IYSNKLM can specifically kill human melanoma cells in vitro and in vivo.

PMID- 20128927
TI  - Escherichia coli genes that reduce the lethal effects of stress.
AB  - BACKGROUND: The continuing emergence of antimicrobial resistance requires the
      development of new compounds and/or enhancers of existing compounds. Genes that
      protect against the lethal effects of antibiotic stress are potential targets of
      enhancers. To distinguish such genes from those involved in drug uptake and
      efflux, a new susceptibility screen is required. RESULTS: Transposon (Tn5)
      mediated mutagenesis was used to create a library of Escherichia coli mutants
      that was screened for hypersensitivity to the lethal action of quinolones and
      counter-screened to have wild-type bacteriostatic susceptibility. Mutants with
      this novel "hyperlethal" phenotype were found. The phenotype was transferable to
      other E. coli strains by P1-mediated transduction, and for a subset of the
      mutants the phenotype was complemented by the corresponding wild-type gene cloned
      into a plasmid. Thus, the inactivation of these genes was responsible for
      hyperlethality. Nucleotide sequence analysis identified 14 genes, mostly of
      unknown function, as potential factors protecting from lethal effects of stress.
      The 14 mutants were killed more readily than wild-type cells by mitomycin C and
      hydrogen peroxide; nine were also more readily killed by UV irradiation, and
      several exhibited increased susceptibility to killing by sodium dodecyl sulfate.
      No mutant was more readily killed by high temperature. CONCLUSIONS: A new
      screening strategy identified a diverse set of E. coli genes involved in the
      response to lethal antimicrobial and environmental stress, with some genes being
      involved in the response to multiple stressors. The gene set, which differed from
      sets previously identified with bacteriostatic assays, provides an entry point
      for obtaining small-molecule enhancers that will affect multiple antimicrobial
      agents.

PMID- 20128928
TI  - Effects of liquid stimuli on dual-axis swallowing accelerometry signals in a
      healthy population.
AB  - BACKGROUND: Dual-axis swallowing accelerometry has recently been proposed as a
      tool for non-invasive analysis of swallowing function. Although swallowing is
      known to be physiologically modifiable by the type of food or liquid (i.e.,
      stimuli), the effects of stimuli on dual-axis accelerometry signals have never
      been thoroughly investigated. Thus, the objective of this study was to
      investigate stimulus effects on dual-axis accelerometry signal characteristics.
      Signals were acquired from 17 healthy participants while swallowing 4 different
      stimuli: water, nectar-thick and honey-thick apple juices, and a thin-liquid
      barium suspension. Two swallowing tasks were examined: discrete and sequential. A
      variety of features were extracted in the time and time-frequency domains after
      swallow segmentation and pre-processing. A separate Friedman test was conducted
      for each feature and for each swallowing task. RESULTS: Significant main stimulus
      effects were found on 6 out of 30 features for the discrete task and on 5 out of
      30 features for the sequential task. Analysis of the features with significant
      stimulus effects suggested that the changes in the signals revealed slower and
      more pronounced swallowing patterns with increasing bolus viscosity. CONCLUSIONS:
      We conclude that stimulus type does affect specific characteristics of dual-axis
      swallowing accelerometry signals, suggesting that associated clinical screening
      protocols may need to be stimulus specific.

PMID- 20128929
TI  - Unscheduled expression of CDC25B in S-phase leads to replicative stress and DNA
      damage.
AB  - BACKGROUND: CDC25B phosphatase is a cell cycle regulator that plays a critical
      role in checkpoint control. Up-regulation of CDC25B expression has been
      documented in a variety of human cancers, however, the relationships with the
      alteration of the molecular mechanisms that lead to oncogenesis still remain
      unclear. To address this issue we have investigated, in model cell lines, the
      consequences of unscheduled and elevated CDC25B levels. RESULTS: We report that
      increased CDC25B expression leads to DNA damage in the absence of genotoxic
      treatment. H2AX phosphorylation is detected in S-phase cells and requires active
      replication. We also report that CDC25B expression impairs DNA replication and
      results in an increased recruitment of the CDC45 replication factor onto
      chromatin. Finally, we observed chromosomal aberrations that are also enhanced
      upon CDC25B expression. CONCLUSION: Overall, our results demonstrate that a
      moderate and unscheduled increase in CDC25B level, as observed in a number of
      human tumours, is sufficient to overcome the S-phase checkpoint efficiency thus
      leading to replicative stress and genomic instability.

PMID- 20128930
TI  - Old divergences in a boreal bird supports long-term survival through the Ice
      Ages.
AB  - BACKGROUND: Unlike northern Europe and most of northern North America, the
      Eastern Palearctic and the northwesternmost tip of North America are believed to
      have been almost unglaciated during the Quarternary glacial periods. This could
      have facilitated long-term survival of many organisms in that area. To evaluate
      this, we studied the phylogeography in east Asia and Alaska of a boreal migratory
      passerine bird, the Arctic Warbler Phylloscopus borealis, and compared our
      results with published data on especially North American species. RESULTS: In a
      sample of 113 individuals from 18 populations we identified 42 haplotypes of the
      mitochondrial cytochrome b gene, which separated into three clades: A--Alaska and
      mainland Eurasia (except Kamchatka); B--Kamchatka, Sakhalin and Hokkaido; and C-
      Honshu, Shikoku and Kyushu (i.e. Japan except Hokkaido). The oldest split among
      these clades, between A/B and C, is estimated to have taken place sometime
      between the mid Pliocene and early Pleistocene, and the second divergence,
      between clades A and B, in the early to mid Pleistocene. Within all of the three
      main clades, there are signs of population expansion. CONCLUSIONS: The Arctic
      Warbler separated into three main clades in close succession around the
      Pliocene/Pleistocene border, with the two northern clades diverging last. All
      three clades probably experienced population bottlenecks during the Pleistocene
      as a result of range shifts and contractions, but nevertheless survived and
      maintained their integrities. Several other clades of Northeastern Palearctic
      birds are noted to have diversified during the Pliocene. In contrast, avian
      species or phylogroups presently occupying formerly glaciated North American
      ground are generally younger. The differences between these regions could be due
      to slower speciation rates in the Eastern Palearctic due to less fragmentation of
      forest habitats during glacial periods, or to longer survival of Eastern
      Palearctic clades as a result of less severe conditions in that region compared
      to northern North America. Several other Palearctic organisms show concordant
      biogeographical patterns to that of the Arctic Warbler, indicating common causes
      of their diversifications.

PMID- 20128931
TI  - Ten years of Genome Biology.
AB  - Huge advances in the field of genomics along with the continued rise of open
      access has made the past ten years an exciting time to be a biologist.

PMID- 20128932
TI  - Assembling genomes using short-read sequencing technology.
AB  - Gigabase-scale genome assemblies are now feasible using short-read sequencing
      technology, bringing the cost of such projects below the million-dollar mark.

PMID- 20128933
TI  - Prospective memory function in mild cognitive impairment and early dementia.
AB  - When compared with controls, both mild cognitive impairment (MCI) and dementia
      are each associated with impaired memory for future intentions, or prospective
      memory (PM). However, prior studies have failed to agree on whether there are
      group differences in PM function between those with MCI and dementia.
      Furthermore, the degree and nature of the impairment remains to be clarified, as
      does the degree to which this impairment is secondary to deficits in other
      aspects of cognition. In the present study, MCI (n = 48), dementia (n = 39), and
      control participants (n = 53) were compared on Virtual Week, a measure that
      closely represents the types of PM tasks that occur in everyday life. Both
      clinical groups exhibited impairment irrespective of the specific task demands,
      but the magnitude of this deficit was greater for those with dementia. After
      covarying for other key cognitive parameters, although the absolute magnitude of
      the deficit was reduced, significant impairment remained. These results indicate
      that individuals with MCI, and to a greater extent dementia, experience
      generalized difficulties with PM. It is suggested that, while other cognitive
      deficits contribute to these difficulties, there is something unique to
      prospective remembering that may be additionally disrupted in these groups.

PMID- 20128934
TI  - Cerebral blood flow velocity and language functioning in pediatric sickle cell
      disease.
AB  - We investigated the association of increased cerebral blood flow velocity with
      specific language abilities in children with sickle cell disease (SCD). Thirty
      nine children ages 5 to 8 years old with high-risk genotypes of SCD underwent
      cognitive testing, which included tests of language skills, visual motor skills,
      and attention/working memory as part of a routine hematology health-maintenance
      visit. Transcranial Doppler (TCD) velocities were obtained from review of medical
      records, with the velocities that were in closest temporal proximity to the
      cognitive assessment used in the analysis. TCD velocities predicted scores on
      tests of syntactical skills, even when controlling for anemia severity. Semantic
      and phonological ability and other cognitive skills were not strongly related to
      TCD velocities. Elevated blood flow velocities in children with high-risk SCD may
      contribute to a specific language impairment or to a broader dysfunction of short
      term and/or working memory. This study underscores the need for clinicians to
      monitor language skills of children with SCD who have elevated TCD velocities, as
      these cognitive abilities might be particularly sensitive to cerebrovascular
      disruption related to their disease.

PMID- 20128935
TI  - Regulatory match effects on a modified Wisconsin Card Sort Task.
AB  - The Wisconsin Card Sorting Task (WCST; Heaton, 1980) is commonly used to assess
      concept formation and set shifting. Cognitive research suggests that set shifting
      performance is enhanced by a match between a person's regulatory focus (promotion
      focus: attempting to earn an entry into a cash drawing; prevention focus:
      attempting to avoid losing an entry into the drawing) and the task reward
      structure (gains: attempting to maximize points gained; losses: attempting to
      minimize points lost). A regulatory match results when attempting to earn an
      entry by maximizing points or attempting to avoid losing an entry by minimizing
      losses. We test the hypothesis that performance on a modified WCST is accentuated
      in younger, healthy participants when there is a match between the global
      performance incentive and the local task reward structure. As predicted,
      participants in a match showed better set shifting but equivalent initial concept
      formation when compared with participants in a mismatch. Furthermore, relative to
      a baseline control group, mismatch participants were significantly worse at set
      shifting than were participants in a regulatory match. These results suggest that
      set shifting performance might be impacted by incentive and task reward factors
      in ways that have not been considered previously.

PMID- 20128936
TI  - Vegetable intake in Korea: data from the Korean National Health and Nutrition
      Examination Survey 1998, 2001 and 2005.
AB  - The purpose of the present study was to analyse vegetable intake by the Korean
      population based on different meal formats. Twenty-four-hour dietary recall data
      from the Korean National Health and Nutrition Examination Survey were used to
      assess daily vegetable intake and consumption ratio of vegetables for different
      meal types/dining locations. Analysis was stratified by sex and age group. Daily
      vegetable intake increased from 293.5 g in 1998 to 305.7 g in 2001 and to 335.9 g
      in 2005. Findings were similar in men and women, as well as in each age group.
      Analyses for each meal type revealed that vegetable intake during breakfast did
      not substantially change, but vegetable intake increased during lunch and dinner.
      While vegetable consumption ratio during breakfast decreased, it increased during
      lunch and snack time. Men and women showed similar change in the analysis for
      meal types and dining locations. There were some differences between the age
      groups in daily vegetable intake depending on the meal type. Another notable
      observation was the increasing change of vegetable intake during lunch and during
      meals eaten at cafeterias and restaurants in all the age groups. Analysis of
      vegetable consumption ratio showed an increased consumption in cafeterias,
      restaurants, and other places and decreased vegetable intake at home for those
      aged 16-64 years with time. Since this change may be related to improvements in
      socioeconomic status, it will be necessary to further investigate difference in
      vegetable intake based on socioeconomic levels within the population.

PMID- 20128937
TI  - Maternal low-protein diet during mouse pre-implantation development induces
      vascular dysfunction and altered renin-angiotensin-system homeostasis in the
      offspring.
AB  - Environmental perturbations during early mammalian development can affect aspects
      of offspring growth and cardiovascular health. We have demonstrated previously
      that maternal gestational dietary protein restriction in mice significantly
      elevated adult offspring systolic blood pressure. Therefore, the present study
      investigates the key mechanisms of blood pressure regulation in these mice.
      Following mating, female MF-1 mice were assigned to either a normal-protein diet
      (NPD; 18 % casein) or an isocaloric low-protein diet throughout gestation (LPD; 9
      % casein), or fed the LPD exclusively during the pre-implantation period (3.5 d)
      before returning to the NPD for the remainder of gestation (Emb-LPD). All
      offspring received standard chow. At 22 weeks, isolated mesenteric arteries from
      LPD and Emb-LPD males displayed significantly attenuated vasodilatation to
      isoprenaline (P = 0.04 and P = 0.025, respectively), when compared with NPD
      arteries. At 28 weeks, stereological analysis of glomerular number in female left
      kidneys revealed no significant difference between the groups. Real-time RT-PCR
      analysis of type 1a angiotensin II receptor, Na+/K+ ATPase transporter subunits
      and glucocorticoid receptor expression in male and female left kidneys revealed
      no significant differences between the groups. LPD females displayed elevated
      serum angiotensin-converting enzyme (ACE) activity (P = 0.044), whilst Emb-LPD
      males had elevated lung ACE activity (P = 0.001), when compared with NPD
      offspring. These data demonstrate that elevated offspring systolic blood pressure
      following maternal gestational protein undernutrition is associated with impaired
      arterial vasodilatation in male offspring, elevated serum and lung ACE activity
      in female and male offspring, respectively, but kidney glomerular number in
      females and kidney gene expression in male and female offspring appear
      unaffected.

PMID- 20128938
TI  - Impact of maternal probiotic-supplemented dietary counselling on pregnancy
      outcome and prenatal and postnatal growth: a double-blind, placebo-controlled
      study.
AB  - The perinatal nutritional environment impacts upon the health and well-being of
      mother and child also in the long term. The aim of the present study was to
      determine the safety and efficacy of perinatal probiotic-supplemented dietary
      counselling by evaluating pregnancy outcome and fetal and infant growth during
      the 24 months' follow-up. Altogether, 256 women were randomised at their first
      trimester of pregnancy into a control and a dietary intervention group. The
      intervention group received intensive dietary counselling provided by a
      nutritionist and were further randomised, double-blind to receive probiotics
      (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12; diet/probiotics) or
      placebo (diet/placebo). Firstly, probiotic intervention reduced the frequency of
      gestational diabetes mellitus (GDM); 13 % (diet/probiotics) v. 36 %
      (diet/placebo) and 34 % (control); P = 0.003. Secondly, the safety of this
      approach was attested by normal duration of pregnancies with no adverse events in
      mothers or children. No significant differences in prenatal or postnatal growth
      rates among the study groups were detected. Thirdly, distinctive effects of the
      two interventions were detected; probiotic intervention reduced the risk of GDM
      and dietary intervention diminished the risk of larger birth size in affected
      cases; P = 0.035 for birth weight and P = 0.028 for birth length. The results of
      the present study show that probiotic-supplemented perinatal dietary counselling
      could be a safe and cost-effective tool in addressing the metabolic epidemic. In
      view of the fact that birth size is a risk marker for later obesity, the present
      results are of significance for public health in demonstrating that this risk is
      modifiable.

PMID- 20128939
TI  - How accurate are adolescents in portion-size estimation using the computer tool
      Young Adolescents' Nutrition Assessment on Computer (YANA-C)?
AB  - Computer-administered questionnaires have received increased attention for large
      scale population research on nutrition. In Belgium-Flanders, Young Adolescents'
      Nutrition Assessment on Computer (YANA-C) has been developed. In this tool,
      standardised photographs are available to assist in portion-size estimation. The
      purpose of the present study is to assess how accurate adolescents are in
      estimating portion sizes of food using YANA-C. A convenience sample, aged 11-17
      years, estimated the amounts of ten commonly consumed foods (breakfast cereals,
      French fries, pasta, rice, apple sauce, carrots and peas, crisps, creamy veloute,
      red cabbage, and peas). Two procedures were followed: (1) short-term recall:
      adolescents (n 73) self-served their usual portions of the ten foods and
      estimated the amounts later the same day; (2) real-time perception: adolescents
      (n 128) estimated two sets (different portions) of pre-weighed portions displayed
      near the computer. Self-served portions were, on average, 8 % underestimated;
      significant underestimates were found for breakfast cereals, French fries, peas,
      and carrots and peas. Spearman's correlations between the self-served and
      estimated weights varied between 0.51 and 0.84, with an average of 0.72. The
      kappa statistics were moderate (>0.4) for all but one item. Pre-weighed portions
      were, on average, 15 % underestimated, with significant underestimates for
      fourteen of the twenty portions. Photographs of food items can serve as a good
      aid in ranking subjects; however, to assess the actual intake at a group level,
      underestimation must be considered.

PMID- 20128940
TI  - Electroglottogram approximate entropy: a novel single parameter for objective
      voice assessment.
AB  - BACKGROUND: The electroglottogram approximate entropy value is a numerical
      variable which gives an overall measure of voice quality. It is derived by
      analysing the complexity of the electroglottogram waveform using regulatory
      statistics. AIMS: (1) To use electroglottogram approximate entropy to measure
      voice quality in patients with glottic pathology and in normal subjects, to
      ascertain whether this parameter can distinguish between pathological and normal
      voices. (2) To ascertain whether electroglottogram approximate entropy can
      measure voice change over time within individual subjects. (3) To determine any
      correlation between electroglottogram approximate entropy and the grade-roughness
      breathiness-asthenia-strain scale. METHODS: One hundred and forty-one normal
      volunteers were recruited to characterise electroglottogram approximate entropy
      in the normal voice. One hundred and eighty-six patients with glottic squamous
      cell carcinoma underwent electroglottogram approximate entropy measurement prior
      to radiotherapy and then three to six months and one year after treatment.
      Subjects' voices were categorised by a speech therapist using the grade-roughness
      breathiness-asthenia-strain scale. RESULTS: The mean electroglottogram
      approximate entropy of the normal volunteers was 0.302 (range 0.05-0.42). The
      mean electroglottogram approximate entropy of the glottic squamous cell carcinoma
      patients was significantly lower prior to treatment, at 0.227 (range 0.001-0.397;
      p < 0.0005), but improved after radiotherapy to 0.277 at three to six months and
      0.282 at one year. Electroglottogram approximate entropy results correlated
      significantly with grade-roughness-breathiness-asthenia-strain scale results.
      CONCLUSION: Electroglottogram approximate entropy can be used to assess change in
      voice quality resulting from glottic morphological abnormality. Electroglottogram
      approximate entropy values improve as voice quality improves after treatment.
      Electroglottogram approximate entropy values correlate significantly with grade
      roughness-breathiness-asthenia-strain scale results.

PMID- 20128941
TI  - Molecular detection of Babesia spp. and other haemoparasitic infections of cattle
      in Maputo Province, Mozambique.
AB  - Molecular detection of Babesia species in apparently healthy cattle within an
      endemic region was carried out in order to determine the prevalence of carriers
      and the geographical distribution of Babesia bigemina and Babesia bovis in Maputo
      Province, Mozambique. Samples from 477 animals at 5 localities were analysed
      using 2 techniques, the semi-nested hot-start PCR and the reverse line blot (RLB)
      assay. With the semi-nested hot-start PCR, detection of B. bigemina ranged
      between 30% and 89%, and of B. bovis between 27% and 83%. The RLB assay was
      comparatively less sensitive in this study and detection of B. bovis ranged from
      0% to 17%, and B. bigemina was not detected at all by this technique. Analysis of
      new sequences of the 18S rRNA gene revealed that the current B. bigemina RLB
      probe is not specific for the identification of isolates in Mozambique. The RLB
      assay, however, resulted in the detection of 8 other haemoparasite species
      belonging to the genera Babesia, Theileria, Anaplasma and Ehrlichia. 18S rRNA
      gene sequences from the Theileria spp. were identified, and a phylogenic tree
      constructed with these sequences yielded a heterogeneous T. mutans-like group. In
      conclusion, infection with B. bigemina and B. bovis is endemic in Maputo
      Province, but rates of transmission vary. Furthermore, mixed infections with the
      haemoparasites responsible for several tick-borne diseases in cattle are common
      in Mozambique.

PMID- 20128942
TI  - Pathways for the influx of molecules into cercariae of Schistosoma mansoni during
      skin penetration.
AB  - It has been observed that fluorescent membrane-impermeant molecules can enter the
      cercariae as they penetrate mouse skin. The hypothesis to be tested was that such
      molecules, which included Lucifer Yellow and a variety of fluorescent dextrans,
      entered the parasite through the nephridiopore and excretory tubules as well as
      through the surface membrane. FITC-labelled poly-L-lysine (molecular weight 10
      kDa), added at 4 degrees C during syringe transformation, was found to enter the
      nephridiopore and labelled the excretory bladder and sometimes the excretory
      tubules. This finding indicates that macromolecules (10 kDa) can enter the
      nephridiopore. It was found that linoleic acid (a normal constituent of skin)
      greatly stimulated uptake of Lucifer Yellow and dextrans into the
      excretory/subtegumental region of 2-h-old schistosomula. This correlated with an
      increased uptake of membrane-impermeant propidium iodide at 37 degrees C. Since
      increased uptake of propidium iodide occurs when membranes become permeable, the
      surface membrane could also be a pathway of transport of the membrane-impermeant
      molecules into the schistosomulum.

PMID- 20128943
TI  - Experimental infection of two South American reservoirs with four distinct
      strains of Trypanosoma cruzi.
AB  - Trypanosoma cruzi (Tc), the causative agent of Chagas disease, is a diverse
      species with 2 primary genotypes, TcI and TcII, with TcII further subdivided into
      5 subtypes (IIa-e). This study evaluated infection dynamics of 4 genetically and
      geographically diverse T. cruzi strains in 2 South American reservoirs, degus
      (Octodon degus) and grey short-tailed opossums (Monodelphis domestica). Based on
      prior suggestions of a genotype-host association, we hypothesized that degus
      (placental) would more readily become infected with TcII strains while short
      tailed opossums (marsupial) would be a more competent reservoir for a TcI strain.
      Individuals (n=3) of each species were intraperitoneally inoculated with T. cruzi
      trypomastigotes of TcIIa [North America (NA)-raccoon (Procyon lotor) origin], TcI
      [NA-Virginia opossum (Didelphis virginiana)], TcIIb [South America (SA)-human],
      TcIIe (SA-Triatoma infestans), or both TcI and TcIIa. Parasitaemias in
      experimentally infected degus peaked earlier (7-14 days post-inoculation (p.i.))
      compared with short-tailed opossums (21-84 days p.i.). Additionally, peak
      parasitaemias were higher in degus; however, the duration of detectable
      parasitaemias for all strains, except TcIIa, was greater in short-tailed
      opossums. Infections established in both host species with all genotypes, except
      for TcIIa, which did not establish a detectable infection in short-tailed
      opossums. These results indicate that both South American reservoirs support
      infections with these isolates from North and South America; however, infection
      dynamics differed with host and parasite strain.

PMID- 20128944
TI  - Copulation enhances resistance against an entomopathogenic fungus in the mealworm
      beetle Tenebrio molitor.
AB  - Ecological immunology is based upon the notion that activation and use of the
      immune system is costly and should thus be traded off against other energy
      demanding aspects of life history. Most of the studies on insects that have
      examined the possibility that mating results in trade-offs with immunity have
      shown that mating has immunosuppressive effects. The connection between mating
      and immunity has traditionally been investigated using indirect measures of
      immunity. However, studies that have assessed the effects of mating on the
      resistance against real pathogens have had conflicting results. A previous study
      on Tenebrio molitor showed that copulation decreases phenoloxidase activity in
      the haemolymph, and concluded that copulation corrupts immunity in this species.
      In the present study we tested whether mating also affects the ability of T.
      molitor to resist the entomopathogenic fungus, Beauveria bassiana. Interestingly,
      we found that mating enhanced resistance against the fungal infection and that
      the effect was stronger on males than females. Furthermore, we found that male
      beetles were overall more susceptible to the fungal infection than were females,
      indicating an immunological sex difference in immunity. Our study highlights the
      importance of the use of real pathogens and parasites in immuno-ecological
      studies.

PMID- 20128945
TI  - Influence of the pseudophyllidean cestode Schistocephalus solidus on oocyte
      development in the threespine stickleback Gasterosteus aculeatus.
AB  - The objective of this study was to investigate the means by which Schistocephalus
      solidus might reduce annual fecundity in female threespine stickleback fish
      (Gasterosteus aculeatus) through processes of oocyte development. Histological
      examinations of specimens from one lake in Alaska in 2000 and 2001 were used to
      analyse the effects of S. solidus on recruitment of primary growth oocytes into
      vitellogenesis, atresia of vitellogenic oocytes, and the interspawning interval.
      The ratio of primary growth to late secondary growth (late vitellogenic) oocytes
      was significantly greater (P<0.01) among infected fish than uninfected ones in
      early-season samples from 2000 and 2001, revealing a decrease in recruitment of
      oocytes from primary growth into vitellogenic oocytes among infected females. The
      difference was marginally non-significant (P=0.087) in a mid-season sample from
      2001 due to reductions in the entire pool of vitellogenic (early and late
      secondary growth) oocytes recruited prior to the spawning season in this
      determinate-fecundity species. Atresia among all vitellogenic oocytes was low and
      did not differ between infected and uninfected females. Histological estimations
      of the interspawning interval using post-ovulatory follicles showed no
      significant differences between infected and uninfected fish, suggesting that the
      number of spawnings in stickleback females each spawning season is unaffected by
      S. solidus infection. Thus, annual fecundity appears to be reduced only through
      recruitment of oocytes into vitellogenesis.

PMID- 20128946
TI  - Identifying high-risk areas of schistosomiasis and associated risk factors in the
      Poyang Lake region, China.
AB  - The epidemiology of schistosomiasis japonicum over small areas remains poorly
      understood, and this is particularly true in China. We aimed to identify high
      risk areas for schistosomiasis and associated risk factors in the Poyang Lake
      region, China. A cross-sectional study was conducted and 60 of 920 persons (6.5%)
      were found to be infected with Schistosoma japonicum. Locations of households and
      snail habitats were determined using a hand-held global positioning system. We
      mapped the data in a geographical information system and used spatial scan
      statistics to explore clustering of infection, logistic regression and Bayesian
      geostatistical models to identify risk factors for each individual's infection
      status and multinomial logistic regression to identify risk factors for living in
      a cluster area. The risk of schistosomiasis was spatially clustered and higher in
      fishermen and males, not in persons who lived in close proximity to snail
      habitats and infected water sources. This study has demonstrated significant
      spatial variation in the prevalence of schistosomiasis at a small spatial scale.
      The results suggest that demographic factors (gender, occupation) rather than the
      distance to infected water are driving human transmission at small-scale spatial
      levels. Such information can be used to plan locally targeted interventions based
      on anthelminthic drug administration, snail control and sanitation improvement.

PMID- 20128947
TI  - Effect of FSH and LH hormones on oocyte maturation of buffalo and gene expression
      analysis of their receptors and Cx43 in maturing oocytes.
AB  - Follicle stimulating hormone (FSH) and luteinizing hormone (LH) are commonly
      added to maturation media to improve cumulus expansion known to be a predictor of
      oocyte maturation. Therefore, effects of various concentrations of FSH (1000
      ng/ml), LH (1000 ng/ml) and FSH + LH (1000 ng/ml each) in comparison with control
      (without FSH + LH) cultured oocytes were investigated. FSH and LH (1000 ng/ml
      each) induced significantly more cumulus expansion and polar body numbers, as
      compared with control and treatments of 1000 ng/ml FSH and 1000 ng/ml LH alone.
      Expression of FSH receptor (r), LHr and Cx43 mRNAs was determined by real-time
      PCR in cumulus-oocyte complexes (COCs) and denuded oocytes at different
      maturation times. Expression of all three genes was higher in COCs compared with
      denuded oocytes, confirming the importance of cumulus cells in oocyte maturation.
      FSHr and connexin 43 (Cx43) mRNA abundance in both COCs and denuded oocytes was
      highest at 0-6 h of maturation and decreased subsequently. However, LHr mRNA
      abundance increased from 6 h up to 24 h of maturation. The study concluded that
      FSH, LH receptors and Cx43 gene expression regulation is an index related to
      oocyte maturation.

PMID- 20128948
TI  - Health anxiety among older people: an exploratory study of health anxiety and
      safety behaviors in a cohort of older adults in New Zealand.
AB  - BACKGROUND: Despite a stereotype that characterizes older people as excessively
      anxious about their health, there is little research into this phenomenon. The
      present exploratory study examined: (a) whether a cohort of older adults was
      unduly health anxious, (b) which demographic and health factors predicted health
      anxiety (HA), and (c) whether an aspect of the cognitive behavioral model of HA
      was applicable to older adults by investigating the relationship between HA and
      safety behaviors. METHOD: Participants were a convenience sample of adults aged
      over 65 and living independently in Auckland, New Zealand. Participants (104
      women and 41 men) completed an anonymous self-report questionnaire measuring
      demographic factors, physical health and function, health anxiety, safety
      behaviors, and medical utilization. RESULTS: This cohort of adults over 65 were
      not unduly health anxious. Occurrence of severe HA was similar to that found in
      younger populations. Decreased physical function and lower education predicted
      scores on the HA measure. Consistent with the cognitive behavioral model, HA was
      a unique significant predictor of safety behaviors. HA and decreased physical
      function predicted medical utilization. CONCLUSIONS: Generally low levels of HA
      among this cohort of older individuals challenged the pervasive stereotype of the
      "hypochondriacal" older person. Factors contributing to HA were similar to those
      reported in studies with younger cohorts. Findings provided preliminary support
      for the applicability of the cognitive behavioral model of HA to adults over 65.
      Implications of the findings and directions for future research were discussed.

PMID- 20128949
TI  - The impact of life review on depression in older adults: a randomized controlled
      trial.
AB  - BACKGROUND: We developed an indicated preventive life-review course, "Looking for
      Meaning", based on the assumption that reminiscence styles influence coping with
      depressive symptoms. This study describes the impact of this course in a
      pragmatic randomized controlled trial. METHODS: Inclusion criteria were >50
      years, a score of 5 or higher on the Center for Epidemiological Studies
      Depression Scale (CES-D), and no depressive disorder or psychotropic or
      psychological treatment. Participants were randomized and stratified by gender:
      the experimental group (N = 83) was offered the course and the comparison group
      (N = 88) a movie. There were three measurements: pre-treatment, post-treatment
      and 6 months after post-treatment. Depressive symptoms constituted the primary
      outcome. Secondary outcomes were anxiety symptoms, satisfaction with life,
      mastery and reminiscence styles. All analyses were conducted according to the
      intention-to-treat principle. Missing values were replaced by regression
      imputation. RESULTS: The course reduced depressive symptoms, a decrease that was
      retained during follow-up. A significant between-group effect size was found (d =
      0.58). There was also a reduction in symptoms of anxiety; however, the comparison
      group showed the same reduction, resulting in a small between-group effect size.
      Gender and level of depressive symptoms were found to be prognostic factors for
      the change in depressive symptoms; age was not. Post hoc analyses showed
      significant between-group effect sizes for females and those with a score above
      the cut-off of the CES-D. CONCLUSION: The course "Looking for Meaning" can be
      recommended for people aged over 50 years, females and older adults with a
      clinically relevant level of depressive symptoms (above cut-off) in particular.

PMID- 20128950
TI  - Family functioning and emotional state two and five years after traumatic brain
      injury.
AB  - Previous studies have documented poor family functioning, anxiety, and depression
      in relatives of individuals with traumatic brain injury (TBI). However, few
      studies have examined family functioning over extended periods after injury. The
      present study aimed to investigate family functioning and relatives' emotional
      state 2 and 5 years following TBI, predictive factors, and their
      interrelationships. Participants were individuals with TBI and their relatives,
      with 301 seen at 2 years and 266 at 5 years post-injury. Measures included a
      Structured Outcome Questionnaire, Family Assessment Device (FAD), Hospital
      Anxiety and Depression Scale, and the Craig Handicap Assessment and Reporting
      Technique. Results showed that while the group did not differ greatly in family
      functioning from a normative group, a significant proportion showed unhealthy
      functioning across most FAD subscales. Both TBI participants and their relatives
      showed elevated rates of anxiety and depression. There was little difference
      between family functioning or relatives' anxiety or depression levels at 2 and 5
      years post-injury. Path analysis indicated that neurobehavioral changes in the
      injured individual have an impact on family functioning and distress in relatives
      even at 5 years post-injury. These findings indicate the need for long-term
      support of families with a brain-injured member.

PMID- 20128951
TI  - Recognizing vocal expressions of emotion in patients with social skills deficits
      following traumatic brain injury.
AB  - Perception of emotion in voice is impaired following traumatic brain injury
      (TBI). This study examined whether an inability to concurrently process semantic
      information (the "what") and emotional prosody (the "how") of spoken speech
      contributes to impaired recognition of emotional prosody and whether impairment
      is ameliorated when little or no semantic information is provided. Eighteen
      individuals with moderate-to-severe TBI showing social skills deficits during
      inpatient rehabilitation were compared with 18 demographically matched controls.
      Participants completed two discrimination tasks using spoken sentences that
      varied in the amount of semantic information: that is, (1) well-formed English,
      (2) a nonsense language, and (3) low-pass filtered speech producing "muffled"
      voices. Reducing semantic processing demands did not improve perception of
      emotional prosody. The TBI group were significantly less accurate than controls.
      Impairment was greater within the TBI group when accessing semantic memory to
      label the emotion of sentences, compared with simply making "same/different"
      judgments. Findings suggest an impairment of processing emotional prosody itself
      rather than semantic processing demands which leads to an over-reliance on the
      "what" rather than the "how" in conversational remarks. Emotional recognition
      accuracy was significantly related to the ability to inhibit prepotent responses,
      consistent with neuroanatomical research suggesting similar ventrofrontal systems
      subserve both functions.

PMID- 20128952
TI  - Locus coeruleus stimulation and noradrenergic modulation of hippocampo-prefrontal
      cortex long-term potentiation.
AB  - Stimulation of the subiculum/CA1 of the hippocampal formation evokes monosynaptic
      field potentials in the prefrontal cortex (PFC). High-frequency stimulation of
      the hippocampus (HPC) can induce long-term potentiation (LTP) in this hippocampo
      prefrontal cortical (hippo-PFC) pathway. Previous studies have shown that
      dopamine and serotonin modulate hippo-PFC LTP. Here, we investigated whether the
      locus coeruleus (LC) and noradrenaline (NA) can modulate LTP in the rat hippo-PFC
      pathway. Stimulation of the LC in combination with stimulation of the HPC
      increased hippo-PFC LTP. Infusion of lidocaine into the LC reduced hippo-PFC LTP.
      Administration of the noradrenaline reuptake inhibitor, nisoxetine or the alpha2
      adrenoceptor antagonist, idazoxan prior to high-frequency stimulation of the HPC
      enhanced hippo-LTP. In contrast, administration of clonidine, an alpha2
      adrenoceptor agonist, impaired hippo-PFC LTP. Partial noradrenergic (NAergic)
      lesioning with DSP-4 also impaired hippo-PFC LTP. In conclusion, the LC and
      NAergic mechanisms modulate hippo-PFC LTP.

PMID- 20128954
TI  - Designing outcome studies to determine efficacy and safety of antipsychotics for
      'real world' treatment of schizophrenia.
AB  - Over the last 5 years, some studies have questioned the efficacy of second
      generation antipsychotics over first-generation neuroleptics in the treatment of
      schizophrenia. At the same time, these study results have led to re-examination
      of their design--particularly CATIE and CUtLASS--which essentially measured
      relatively short-/mid-term outcome and did not always take into account real
      world clinical practice and outcome measures (e.g. prevalence of positive acute
      symptoms, exclusion of comorbidity with substance abuse, predominance of chronic
      patients, lack of quality of life/wellbeing measures, etc.). In fact, one of the
      greatest challenges to treatment of schizophrenia is its life-long, multifaceted,
      functional disability associated with progressive cognitive deterioration after
      each acute episode. As such, the most important goal of the treatment is not just
      to deal with acute episodes, but rather to improve long-term outcome.
      Specifically, we aim for modest improvement and then stabilization of the
      different clinical dimensions involved in the overall symptomatology (i.e.
      negative/anergic, impulsive, positive, mood and cognitive impairments), and to
      achieve 'clinical stabilization' after obtaining a partial or full remission of
      acute symptoms, thus reducing the risk of a progressive cognitive deterioration.
      All these aspects need to be properly evaluated in a long-run perspective.

PMID- 20128955
TI  - Safety, tolerability and preliminary evidence for antidepressant efficacy of
      theta-burst transcranial magnetic stimulation in patients with major depression.
AB  - The aim of this open study was to evaluate the safety and tolerability of theta
      burst transcranial magnetic stimulation (TBS) and to assess preliminarily its
      therapeutic efficacy in patients with major depression. A total of 33 patients
      were assigned to receive one of four TBS protocols for 10 consecutive work days.
      TBS consisted of triple-pulse 50-Hz bursts given at a rate of 5 Hz to the left or
      right dorsolateral prefrontal cortex at different stimulation parameters.
      Severity of depression was assessed by the Hamilton Depression Rating Scale. Our
      results indicate that TBS as applied in this study is safe and well tolerated in
      depressed patients and seems to have antidepressant properties. Increase of
      stimulation parameters is not associated with more side-effects and adds to its
      therapeutic effect.

PMID- 20128953
TI  - Level of response and safety of pharmacological monotherapy in the treatment of
      acute bipolar I disorder phases: a systematic review and meta-analysis.
AB  - In recent years, combinations of pharmacological treatments have become common
      for the treatment of bipolar disorder type I (BP I); however, this practice is
      usually not evidence-based and rarely considers monotherapy drug regimen (MDR) as
      an option in the treatment of acute phases of BP I. Therefore, we evaluated
      comparative data of commonly prescribed MDRs for both manic and depressive phases
      of BP I. Medline, PsycINFO, EMBASE, the Cochrane Library, the
      ClinicalStudyResults.org and other data sources were searched from 1949 to March
      2009 for placebo and active controlled randomized clinical trials (RCTs). Risk
      ratios (RRs) for response, remission, and discontinuation rates due to adverse
      events (AEs), lack of efficacy, or discontinuation due to any cause, and the
      number needed to treat or harm (NNT or NNH) were calculated for each medication
      individually and for all evaluable trials combined. The authors included 31 RCTs
      in the analyses comparing a MDR with placebo or with active treatment for acute
      mania, and 9 RCTs comparing a MDR with placebo or with active treatment for
      bipolar depression. According to the collected evidence, most of the MDRs when
      compared to placebo showed significant response and remission rates in acute
      mania. In the case of bipolar depression only quetiapine and, to a lesser extent,
      olanzapine showed efficacy as MDR. Overall, MDRs were well tolerated with low
      discontinuation rates due to any cause or AE, although AE profiles differed among
      treatments. We concluded that most MDRs were efficacious and safe in the
      treatment of manic episodes, but very few MDRs have demonstrated being
      efficacious for bipolar depressive episodes.

PMID- 20128956
TI  - Eliminating drug price differentials across government programmes in the USA.
AB  - Federal agencies in the USA pay significantly different prices for the same
      prescription drugs because each agency uses a different approach to derive the
      payment rate. Because we do not identify any economic rationale or socially
      accepted moral reasoning that would justify the current level of price variation,
      we suggest that the federal government should pay a uniform price for each drug.
      Laws and regulations that give certain federal agencies the ability to earn
      rebates, use formularies, or permit other special arrangements would need to be
      eliminated in order to have a single payment rate. This could make some
      government agencies worse off than others; however, a uniform payment rate would
      not need to affect beneficiaries' current financial contributions, access to
      drugs, benefits or overall public expenditures. At the same time, having a single
      rate would permit the government to adopt a more effective approach to purchasing
      drugs and send a consistent message to pharmaceutical companies concerning which
      types of drugs the government wants them to develop for government beneficiaries.
      How this single price would be derived and how it would compare with the lowest
      or highest prices currently achieved by government agencies would depend on a
      variety of policy issues including the government's desire to encourage
      pharmaceutical research and development and the need to control health care
      spending.

PMID- 20128957
TI  - I want it and I want it now: using a temporal discounting paradigm to examine
      predictors of consumer impulsivity.
AB  - This paper proposes a new model of consumer impulsivity, using type of good, a
      person's endorsement of materialistic values, and identity deficits as
      predictors. Traditional decision making and psychological accounts see impulsive
      behaviour as a general overweighing of short-term gratification (I want that
      dress now) relative to longer-term concerns, irrespective of consumer good. Our
      proposal is that consumers' impulsivity (a) differs according to type of good and
      (b) is linked systematically to a combination of materialistic values and high
      identity deficits. Beginning with Study 1, three experiments, using a temporal
      discounting paradigm, show consistently that discount rates are higher for goods
      that are seen as highly expressive of identity (e.g., clothes) than goods not
      expressive of identity (e.g., basic body care products). For materialistic
      consumers, identity deficits predict discount rates for identity-expressive goods
      (Study 2), and discount rates change for materialistic individuals when their
      identity deficits are made salient (Study 3). These findings support a
      conceptualization of consumer impulsivity as identity-seeking behaviour.

PMID- 20128958
TI  - Processing and memory of information presented in narrative or expository texts.
AB  - BACKGROUND: Previous research suggests that narrative and expository texts differ
      in the extent to which they prompt students to integrate to-be-learned content
      with relevant prior knowledge during comprehension. AIMS: We expand on previous
      research by examining on-line processing and representation in memory of to-be
      learned content that is embedded in narrative or expository texts. We are
      particularly interested in how differences in the use of relevant prior knowledge
      leads to differences in terms of levels of discourse representation (textbase vs.
      situation model). SAMPLES: A total of 61 university undergraduates in Expt 1, and
      160 in Expt 2. METHODS: In Expt 1, subjects thought out loud while comprehending
      circulatory system content embedded in a narrative or expository text, followed
      by free recall of text content. In Expt 2, subjects read silently and completed a
      sentence recognition task to assess memory. RESULTS: In Expt 1, subjects made
      more associations to prior knowledge while reading the expository text, and
      recalled more content. Content recall was also correlated with amount of relevant
      prior knowledge for subjects who read the expository text but not the narrative
      text. In Expt 2, subjects reading the expository text (compared to the narrative
      text) had a weaker textbase representation of the to-be-learned content, but a
      marginally stronger situation model. CONCLUSIONS: Results suggest that in terms
      of to-be-learned content, expository texts trigger students to utilize relevant
      prior knowledge more than narrative texts.

PMID- 20128959
TI  - [Association between IgG antibody against the C-terminal region of the preS1
      protein of hepatitis B virus and the early response to interferon therapy in
      chronic hepatitis B].
AB  - OBJECTIVE: To determine the relationship between IgG antibody against the C
      terminal region of the preS1 protein of hepatitis B virus and the early response
      to interferon therapy in chronic hepatitis B. METHODS: 69 patients with chronic
      hepatitis B virus (genotype B) infection were recruited in this study. 42
      patients were treated with interferon-a-1b or a-2b, and 27 patients were treated
      with PEG interferon (a-2a). Peptide mimicking the C-terminal region of the preS1
      protein (94-117aa) of genotype B HBV were synthesised, and the IgG antibody
      against this peptide was measured by ELISA, and the early response to IFN-alpha
      therapy was judged by the effect on the viral kinetics, transaminase and the
      status of HBeAg at 12th week after the treatment. RESULTS: 21 patients were
      positive for anti-preS1 antibody, and 48 patients were negative for anti-preS1
      antibody. After 12 weeks of the treatment, the average decrease in viral levels
      was 3.37log10 copies/ml and 0.33log10 copies/ml in anti-PreS1 positive patients
      and anti-preS1 negative patients, respectively, the difference between the two
      groups was significant (Z = -3.658, P = 0.000); the average decrease in ALT
      levels was 92 U/L and 30.5 U/L in these two groups, respectively (Z = -2.132, P =
      0.033). The rate of hepatitis B e antigen (HBeAg) loss was 41.2% (7/17) and the
      rate of anti-HBe seroconversion was 5.9% (1/17) in anti-PreS1 positive group,
      however, the rate of hepatitis B e antigen loss was only 12.8% (5/39), and none
      of the patients in anti-PreS1 negative group showed anti-HBe seroconversion, the
      difference between the two groups was significant (Z = -5.110, P = 0.000). The
      rates of response were 71.4% (15/21) and 16.7% (8/48), respectively, in anti
      PreS1 positive group and anti-PreS1 negative group. The rates of complete
      response were 23.8% (5/21) and 6.25% (3/48), respectively, in these two groups.
      The positive predictive value (PPV) of anti-C-terminal region of preS1 (94-117aa)
      antibody in predicting early response was 71.6% and the negative predictive value
      (NPV) was 83.3%. CONCLUCIONS: Detection of anti-C-terminal region of preS1 (94
      117aa) antibody may help to improve the efficacy of INF-alpha therapy for chronic
      hepatitis B (CHB).

PMID- 20128960
TI  - [Expression and subcellular localization of APOBEC3G in peripheral blood
      mononuclear cells and liver tissues of chronic HBV patients].
AB  - OBJECTIVE: To study the expression level and intracellular localization of
      APOBEC3G in peripheral blood mononuclear cells (PBMCs) and liver tissues of
      chronic HBV patients. METHODS: The expression level and intracellular
      localization of APOBEC3G in PBMCs and liver tissues were detected using the
      western blot and confocal laser scanning microscope (CLSM). RESULTS: Western-blot
      showed that the expression level of APOBEC3G in PBMCs of healthy controls was
      very low. The relative expression levels of APOBEC3G in PBMC of patients with
      chronic hepatitis B, chronic severe hepatitis, liver cirrhosis, or liver cancer
      were 4.12+/-0.21, 4.07+/-0.28, 4.16+/-0.36 or 4.21+/-0.39 respectively, which
      were higher than that in the healthy controls. However, there was no significant
      difference in APOBEC3G expression among different chronic HBV patients (q =
      0.931, 0.744, 1.675, 1.675, 2.606 or 0.931, respectively, all P values more than
      0.05). In addition, there was no significant difference on APOBEC3G in liver
      tissues between chronic hepatitis B patients and hepatocellular carcinoma
      patients (4.40+/-0.34 vs 4.34+/-0.43, q = 0.588, P more than 0.05). CLSM
      indicated that the localization of APOBEC3G protein was in cytoplasm of PBMCs and
      hepatocytes. CONCLUSION: APOBEC3G is upregulated in the PBMCs of chronic
      hepatitis B patients.

PMID- 20128961
TI  - [Inhibitory effect of anluohuaxianwan on experimental hepatic fibrosis in rats].
AB  - OBJECTIVE: To investigate the effects of anluohuaqianwan on experimental hepatic
      fibrosis induced by dimethyl nitrosamine (DMN) in rats. METHODS: 36 male SD rats
      were randomly dividied into three groups: model group, normal group,
      anluohuaqianwan group. The rats in the three groups were treated with DMN daily
      for 4 weeks. The liver function was detected using auto biochemistry analyzer,
      the serum HA, LN, IV-C, PIIIP were detected by immunoradiometry, the
      histopathology was observed in the left liver lobe after HE staining, the
      expression of matrix metalloproteinase-2 (MMP-2) in liver tissue were detected by
      immunohistochemistry. RESULTS: The serum levels of ALT, AST, ALP, TP, ALB and the
      contents of HA, LN, IV-C in model group were significantly increased compared to
      these in the normal group (P less than 0.01). The serum levels of ALT, AST and
      the contents of HA in anluohuaqianwan group were significantly lower than those
      in the model group (P less than 0.01). The liver MMP-2 in the model group was
      significantly increased compared to that in the normal group (P less than 0.05).
      The expression of MMP-2 in liver tissue of model group was lower than that in the
      anluohuaqianwan group (P less than 0.05). CONCLUSION: Anluohuaqianwan can inhibit
      liver fibrosis in rats induced by DMN.

PMID- 20128962
TI  - [Huangqi decoction inhibits cholangiocyte proliferation and transdifferentiation
      in cholestatic liver fibrosis induced by BDL in rats].
AB  - OBJECTIVE: To elucidate the antifibrotic mechanism of Huangqi decoction in rats
      with BDL-induced cholestatic liver fibrosis. METHODS: Liver fibrosis model was
      induced by ligating the common bile duct (BDL) in rats. Sham-operation was
      performed in control rats. The BDL rats were randomly divided into two groups:
      the BDL group and the Huangqi decoction group. Huanqi decoction was given
      intragastrically for 4 weeks. At the end of the fifth week after BDL, animals
      were sacrificed. RESULTS: Compared with the sham control group, mortality rate in
      BDL group was 33.3% and incidence rate of ascites was 90%, and hepatic function
      was abnormal in most of the rats in BDL group. The number of Hepatocytes was
      decreased and the number of cholangiocytes significantly increased in BDL group.
      In addition, Hyp content of liver tissue and protein expression of CK 7 and a-SMA
      were significantly increased. Immunostaining indicated that CK 7 and a-SMA were
      co-localized in BDL group. These changes were markedly suppressed by the Huangqi
      decoction. CONCLUSIONS: These observations suggest that Huangqi decoction can
      inhibit cholangiocyte proliferation and cholangiocyte transdifferentiation.

PMID- 20128963
TI  - [Comparison of the metastatic characteristics of HCCLM3 cells and SMCC-7721 cells
      in nude mice model].
AB  - OBJECTIVE: To compare the metastatic characteristics of HCCLM3 cells and SMCC
      7721 cells in nude mice model. METHODS: Nude mice were divided into two groups (n
      = 8, each), mice were transplanted with HCCLM3 cells (group A) and SMMC-7721
      cells (group B). Tumor size, metastasis rate and other clinical parameters were
      compared between the two groups. Statistical analysis was performed with the help
      of SPSS 16.0 for Windows computer software (SPSS, Inc., Chicago, IL). P values of
      less than 0.05 were considered statistically significant. RESULTS: Intrahepatic
      metastases rate was 100% (8 / 8), mean intrahepatic primary tumor volume was
      (6954+/-1945) mm(3) in group A, Intrahepatic metastases rate was 62.5% (5/8), and
      mean intrahepatic primary tumor volume was (6034+/-2035) mm(3) in the group B.
      There was no statistical difference in the primary liver tumor size and
      intrahepatic metastases rate (P = 0.20; t = 6.38, P = 0.37, respectively). The
      numbers of intrahepatic metastases and the involved lobes, and the volume of
      tumor were 4.5 (median), 3, and 975 mm(3) (median) respectively, in group A, and
      these were 1 (median), 1 and 274 mm(3) (median) respectively in group B. The
      difference between two groups was statistically significant (Z values, -2.818, 
      2.289, and -1.975, respectively).The rate of lung metastasis and other organ
      metastasis in the A group was significantly higher than that in group B (P less
      than 0.001, P less than 0.041, respectively). CONCLUSION: HCCLM3 cells have
      higher metastatic potential than SMMC-7721 cells in nude mice.

PMID- 20128964
TI  - [Comparison of the Golgi proteome of hepatocellular carcinoma with that of the
      adjacent non-tumor tissues].
AB  - OBJECTIVE: To compare the Golgi proteome of hepatocellular carcinoma (HCC) with
      that of the adjacent non-tumor tissues. METHODS: Hepatocellular carcinoma and
      adjacent non-tumor tissues were obtained from HCC patients. The protein
      expression maps in Golgi were obtained by two-dimensional gel electrophoresis (2
      DE), and the differentially expressed protein spots were analyzed by PD-Quest
      software. Peptide mass fingerprint (PMF) of differential protein spots was
      obtained with MALD-TOT-MS. RESULTS: According to 2-DE maps, the average numbers
      of protein spots were (1153+/-49) and (1086+/-37) in hepatocellular carcinoma and
      the adjacent non-tumor tissues. Compared to the adjacent non-tumor tissues, 27
      proteins were upregulated, and 20 proteins were downregulated in HCC Golgi.
      CONCLUSIONS: The Golgi proteome in HCC tissues is different from that in the
      adjacent non-tumor tissues, and the differential expression proteins are involved
      in energy metabolism, tumor metastasis, and cell cycle regulation.

PMID- 20128965
TI  - [Effects of ARNT2 gene on invasion and migration of human hepatocellular
      carcinoma HCCLM6 cell line].
AB  - OBJECTIVE: To investigate the effects of ARNT2 on invasion and migration of
      HCCLM6 cells. METHODS: Four short hairpin oligos targeting to ARNT2 were s cloned
      into the pLVTHM vector. Lentiviral vectors shRNA-ARNT2i, pCMV-dR8.74 and pMD2G
      were cotransfected into 293T cells using Lipofectamine 2000. HCCLM6 was infected
      with virus supernatant. ARNT2 mRNA and protein expressions were detected using
      quantitative Real time-PCR and Western blot, respectively. The invasion and
      migration of HCCLM6 cells were evaluated using wound healing assay and cell
      invasion assay in vitro. Statistical analysis was performed with SPSS 16.0.
      RESULTS: The relative mRNA levels of ARNT2 were 0.154+/-0.024, 0.860+/-0.145,
      1.004+/-0.009 in shRNA-ARNT2i virus infected HCCLM6 cells, mock-infected cells
      and control vector virus infected cells (F = 113.14, P more than 0.01). The
      expression of ARNT2 at protein level was 16.45+/-1.6, 44.56+/-2.07 in the HCCLM6
      cells infected with shRNA-ARNT2i virus and negative control vector virus,
      respectively (t = 18.58, P less than 0.01). The scrape wound of HCCLM6 cells
      infected with shRNA-ARNT2i virus healed faster than cells infected with control
      vector virus or mock-infected cells. The number of cells invading through
      Matrigel was higher in the HCCLM6 cells infected with shRNA-ARNT2i virus (13.25+/
      1.04) than that in mock-infected HCCLM6 cells and the HCCLM6 cells infected with
      negative control vector virus (6.50+/-2.56, 6.75+/-2.05) (F = 29.645, P less than
      0.01). CONCLUSION: Inhibition of ARNT2 gene promotes the invasion and migration
      of HCCLM6 cells.

PMID- 20128966
TI  - [Effects of HBsAg pulsed dendritic vaccination on anti-HBs production in
      immunosuppressed rats after liver transplantation].
AB  - OBJECTIVE: To explore the effects of HBsAg pulsed dendritic vaccination on anti
      HBs production in immunosuppressed rats after liver transplantation (LT).
      METHODS: Brown-Norway liver allografts were transplanted into Lewis recipients.
      The transplanted Lewis rats were injected with EK506 (2 mg/kg) and randomly
      divided into two groups: rats in HBsAg-DCs group (n = 15) were intraperitoneally
      injected with HBsAg pulsed DCs at 14 d and 28 d after LT, and rats in the HBsAg
      group (n = 15) were injected with HBsAg (200 mul) once a week for 12 weeks. Rats
      without any immunosuppressive treatment after LT served as controls (n = 5). IL-2
      and IFN-gamma mRNA expression in spleen were analyzed by RT-PCR, serum IL-2, IFN
      gamma and anti-HBs were detected by ELISA. RESULTS: High dose of FK506 resulted
      in the immunosuppressed in LT rats, as evident by low production of IL-2 and IFN
      gamma, and without liver rejection compared to rats in the control group. HBsAg
      DCs induced high titer of anti-HBs antibody, however, titer of anti-HBs were
      seldom detectable in the HBsAg group at 1, 2 and 3 mouth after vaccination.
      CONCLUSION: The capacity of HBsAg-DCs to induce anti-HBs in immunosuppressed rats
      suggested that DC vaccine may prevent HBV recurrence in liver transplanted
      patients.

PMID- 20128967
TI  - [Clinical significance of liver function and autoantibodies in patients with
      acute or chronic drug-induced liver injury].
AB  - OBJECTIVE: To investigate the clinical significance of liver function and
      autoantibodies in patients with acute or chronic drug-induced liver injury.
      METHODS: 51 patients with drug-induced liver injury were divided into acute drug
      induced liver injury group and chronic drug induced liver injury group, liver
      function and autoantibodies were compared between these two groups. RESULTS:
      There was no significant difference (P more than 0.05) in alanine
      aminotransferase [(412.1+/-387.5) U/L and (376.0+/-319.7) U/L], aspartate
      aminotransferase [(352.5+/-457.9) U/L and (198.8+/-142.7) U/L], total bilirubin
      [(109.7+/-104.80)micromol/L and(102.4+/-135.7)micromol/L], direct bilirubin
      [(66.4+/-73.3)micromol/L and (61.2+/-72.1)micromol/L], alkaline phosphatase
      [(133.4+/-50.1) U/L and (147.4+/-97.3) U/L], gamma-glutamyltransferase [(139.9+/
      134.1) U/L and (180.6+/-227.9) U/L], and albumin [(41.3+/-4.9) g/L and (39.8+/
      5.3)g/L] between these two groups, however, the level of globulin [(25.1+/-5.3)
      g/L and (28.6+/-5.1) g/L] was significantly different between these two groups (P
      less than 0.05). The titers of Anti-nuclear antibody (ANA) and smooth muscle
      antibody (SMA) were less than or equal to 1:320 in patients with acute drug
      induced liver injury. The titers of ANA, antimitochondrial antibody (AMA), and
      SMA were more than or equal to 1:320 in most of the patients with chronic drug
      induced liver injury. CONCLUSION: Liver function has no value in the diagnosis of
      acute or chronic drug induced liver injury. High titer autoantibodies are found
      in patients with chronic drug induced liver injury.

PMID- 20128968
TI  - [Therapeutical effect of combined hepatic resection and fenestration on patients
      with severe adult polycystic liver disease].
AB  - OBJECTIVE: To evaluate therapeutical effect of combined hepatic resection and
      fenestration on patients with severe adult polycystic liver disease (APLD).
      METHODS: Preoperative clinical symptoms, postoperative complications and
      prognoses from 33 patients with severe adult polycystic liver disease (APLD)
      treated with combined hepatic resection and fenestration were recorded. According
      to the number and location of cysts before surgery and the remnant liver
      parenchyma after operation, all patients were classified into two types: class A
      and B. And patients in each type were further classified into three grades: Grade
      I, II and III. The frequency of postoperative complications of two types patients
      was compared. RESULTS: The mean follow-up time was 57 months. There were three
      patients with recurrence of symptoms at 81, 68 and 43 mouths after operation. Two
      patients died of renal failure due to polycystic kidney disease at 137 and 85
      mouths after operation. And one patient with postoperative hepatic inadequacy
      received an orthotopic liver transplantation. The total number of patients with
      postoperative complications was 26 cases, including one patient with bleeding,
      two patients with bile leakage, fourteen patients with mild ascites, twelve
      patients with severe ascites and eighteen patients with pleural effusion, and the
      overall incidence was 78.8%. There were 22 patients with imaging data, including
      6 patients within A type and sixteen patients within B type. The frequencies of
      postoperative complications were 4 and 31, respectively, and the difference was
      statistically significant (Chi-square test = 4.99, P less than 0.05). CONCLUSION:
      Combined hepatic resection and fenestration is a safe and acceptable procedure
      for the treatment of severe APLD.

PMID- 20128969
TI  - [Analysis of the relationship between hepatorenal syndrome and plasma ammonia].
AB  - OBJECTIVE: To analyze the relationship between hepatorenal syndrome (HRS) and
      plasma ammonia. METHODS: Plasma ammonia, liver and renal function of 465 patients
      with liver cirrhosis in our hospital, from June 2007 to March 2009, were
      analyzed. 80 renal dysfunction patients and 80 healthy controls were recruited in
      the control group. In addition, 40 patients with HRS were followed up. RESULTS:
      Using urea as the diagnosis standard of HRS, the morbidity rate of HRS was 39.6%,
      which was higher than that using creatinine as the diagnosis standard of HRS (Chi
      square test = 97.33, P less than 0.01). using urea and creatinine as the
      diagnosis standard of HRS, the ammonia level of HRS groups was (57.39+/
      48.83)mumol/L, (64.80+/-47.25)mumol/L, which were higher than that in the non-HRS
      groups (t = -3.07, t = -3.67, P less than 0.01). The ammonia level of patients
      with renal dysfunction was (26.59+/-14.34)mumol/L, which was lower than that in
      HRS group, non-HRS group (P less than 0.01), but there was no statistical
      significance between the patients with renal dysfunction and the healthy peoples
      [(22.36+/-8.72)mumol/L] (t = 1.52, P more than 0.05). The followed-up analysis of
      40 patients with HRS indicated that plasma ammonia level was positively
      correlated with urea and creatinine, and correlation coefficients were 0.874 and
      0.834 (P less than 0.05). CONCLUSION: Hepatic encephalopathy is liver-kidney
      intestine-brain syndrome. HRS plays an important role in the development of
      hepatic encephalopathy.

PMID- 20128970
TI  - [The reassessment of the diagnostic value of 24-hour urinary copper excretion in
      children with Wilson's disease].
AB  - OBJECTIVE: To reassess the diagnostic value of 24 hour urinary copper excretion
      in children with Wilson disease (WD). METHODS: From July 2005 to June 2007,
      inpatients over three years old in a pediatric liver center were assigned into WD
      and non-WD group. RESULTS: 94 patients, including 26 cases in WD and 68 in non-WD
      group, were enrolled in this study. The median of 24 h urinary copper excretion
      was 98.5 microg in WD group and 25.8 microg in the non-WD group (Z = -6.111, P
      equal to 0.000). The area under receiver operator curve (ROC) was 0.909 (95% CI:
      0.839-0.979, P equal to 0.000). The sensitivity, specificity, accuracy, positive
      predictive value and negative predictive value were 84.6%, 91.2%, 89.4%, 78.6%
      and 93.9% respectively using 52.0 ug as a cutoff value, and 50.0%, 97.1%, 84.0%,
      86.7% and 83.5% using 100 microg as a cutoff value. The goodness of fitness of 52
      microg criteria was significantly higher than 100 microg criteria
      (kappacoefficient 0.760, 0.541 respectively, P equal to 0.000). CONCLUSION:
      Comparing to 100, 52 microg of 24 h urinary copper excretion as a cutoff value
      significantly improves the sensitivity and accuracy for diagnosing WD in
      children.

PMID- 20128971
TI  - [Metabolic characteristics of a fatty liver disease model induced by high-fat
      feeding in young rats].
AB  - OBJECTIVE: To establish nonalcoholic fatty liver disease (NAFLD) in young rats,
      and to investigate the metabolic characteristics of these rats. METHODS: Fifteen
      male and fifteen female SD rats of 3 weeks old were randomly divided into three
      groups, normal group (N), 20% high fat group (HF1) and 30% high fat group (HF2).
      All the rats were fed under Specific pathogen Free (SPF) condition for 6 weeks
      and executed at the end of the 6th week. Body length and weight of each rat as
      well as their liver weight were measured for calculating Liver Index (LI). ALT,
      AST, TG, TC, INS, Glu and HOMA-IR in the blood were measured. Liver tissue
      homogenate was prepared for detecting TG level. The liver section was stained
      with HE and oil red. The expression of SPEBP-1 and leptin in liver was detected
      by immunostaining. RESULTS: The typical pathological change of NAFLD was found in
      the rats of HF groups. In HF2 group, no rats died during the experiment and the
      degree of fat degeneration is homogeneous. Comparing with those in N group, TC
      (mmol/L), liver TG (mmol/L) and ALT levels in HF2 group were significantly
      elevated (2.50+/-0.39 vs 1.82+/-0.43, P less than 0.01; 25.38+/-13.29 vs 12.09+/
      9.59, P less than 0.01 and 69.80+/-18.22 vs 48.00+/-10.45, P less than 0.01,
      respectively). Comparing with those in N group, TG level in HF1 group was
      significantly decreased (0.17+/-0.10 vs 0.32+/-0.12, P less than 0.05), Glu level
      in HF1 group was significantly elevated (12.33+/-3.48 vs 8.13+/-2.53, P less than
      0.05). There were no significant difference between the results of AST, INS and
      HOMA-IR among the groups. The expression level of SREBP-1 and leptin increased in
      HF groups. CONCLUSION: NAFLD can be induced by 30% high-fat feeding for 6 weeks
      in young rats, high-fat feeding induces the expression of SREBP-1 and leptin
      expression and fat synthesis.

PMID- 20128972
TI  - [Safety and short-term effect of antithyroid agents on hyperthyroidism patients
      coexisting with viral hepatitis].

PMID- 20128973
TI  - [Expression of TLR9 in peripheral blood mononuclear cells of hepatitis B
      patients].

PMID- 20128974
TI  - [Status of hepatitis C in Guangzhou from 2005 to 2008].

PMID- 20128975
TI  - [Comparison of efficacy between adefovir dipivoxil and entecavir in patients with
      chronic hepatitis B].

PMID- 20128976
TI  - [Expressions of MDM2 and MMP-7 in normal liver, cirrhosis, hepatocellular
      carcinoma tissues].

PMID- 20128977
TI  - [Effect of different doses of losartan on cirrhotic portal hypertensive colopathy
      in rats].

PMID- 20128978
TI  - [A case report of systematic amyloid with hepatic function abnormal].

PMID- 20128979
TI  - [A case report of immature hepatic teratoma].

PMID- 20128980
TI  - [A brief report on the third national congress of fatty liver disease and summit
      forum of Hong Kong, Taiwan and mainland China].

PMID- 20128981
TI  - [Advance in clinical studies of the kinetics of hepatitis B virus].

PMID- 20128982
TI  - [The role of LPS/TLR4 interaction on the pathogenesis of acute on chronic liver
      failure].

PMID- 20128983
TI  - Mycosis fungoides in the pediatric population: report from an international
      Childhood Registry of Cutaneous Lymphoma.
AB  - BACKGROUND/OBJECTIVES: There are limited data on the clinical presentation and
      progression of pediatric cutaneous lymphoma. This study focuses on the clinical
      characteristics of pediatric patients with mycosis fungoides (MF). MATERIALS AND
      METHODS: This descriptive study presents clinical characteristics of 22 pediatric
      patients with MF, enrolled in the international Childhood Registry for Cutaneous
      Lymphomas (CRCL). RESULTS: The mean ages at onset and at diagnosis were 7.5 (SD
      3.8 years) years and 9.9 (SD 3.4) years, respectively. The most common MF
      presentation was patch stage (68%), followed by hypopigmentation (59%) and plaque
      stage disease (50%). Epidermotropism and lymphocytic atypia were the most common
      pathologic features, found in 89% and 85%, respectively. Cerebriform nuclei were
      noted in 42%, and Pautrier microabscesses were seen in 16% of cases. A cytotoxic
      pattern was more commonly seen (67% vs 33%), and clonality was detected in 21% (3
      of 14) of patients. All patients presented with early-stage disease and received
      skin-directed therapy (topical steroids, 73%; light therapy, 54%; or combination
      therapy, 35%). CONCLUSIONS: Pediatric patients with MF present in the first
      decade of life, with early-stage disease and unusual forms such as hypopigmented
      variant. Further patient enrollment will provide information regarding natural
      history, treatment response, and overall prognosis of pediatric cutaneous T-cell
      lymphoma (CTCL).

PMID- 20128984
TI  - Evaluation of a telehealth clinic as a means to facilitate dermatologic
      consultation: pilot project to assess the efficiency and experience of
      teledermatology used in a primary care network.
AB  - BACKGROUND: Primary care offices spend considerable time coordinating the
      specialist referral process. Patients experience long wait times for consultation
      and intervention. OBJECTIVE: To determine if telehealth combined with
      interdisciplinary team-based care can reduce wait times for dermatologic
      consultation while making the consultation process easier for physicians.
      METHODS: Retrospective chart reviews as well as patient, referring physician,
      nonreferring physician, clinic physician, nurse, and teledermatologist interviews
      were used to evaluate the clinic. A comparative immersion approach generated
      themes from field notes. Wait times, appointment times, and encounter durations
      were measured. RESULTS: Twenty-eight patients were seen (23 had previous
      specialist referral experience) within 1 week of referral compared to a wait
      period of 104 days for conventional referral. Patients requiring intervention
      were treated within 1 week of their initial appointment. Referring practitioners
      were concerned that they would lose control of patients' care. An easier referral
      process and faster intakes met physician expectations. CONCLUSIONS:
      Teledermatology improves the timeliness of appointments. Patients forgo face-to
      face appointments if alternatives are available sooner. Physicians are concerned
      about their own liability if dermatologists do not assess the patient in person
      but will refer through teledermatology when patients are seen faster and they
      remain in control of the care process.

PMID- 20128985
TI  - Children with atopic dermatitis do not have more anxiety or different cortisol
      levels compared with normal children.
AB  - BACKGROUND: The hypothalamic-pituitary-adrenal axis has an important
      immunoregulatory role under stress, and stress-mediated anxiety has been reported
      to be associated with alterations in immune functions and attenuated cortisol
      levels in atopic dermatitis (AD) patients. OBJECTIVE: We investigated serum basal
      cortisol and anxiety levels in pediatric AD patients and compared them with those
      of controls. METHODS: Basal serum cortisol levels were measured in 36 pediatric
      AD patients (aged 9-16 years) and 36 control subjects (aged 9-15 years). Anxiety
      was assessed by the trait anxiety subscale (TAI-C) of the State-Trait Anxiety
      Inventory for Children. The severity of AD was assessed by the objective severity
      scoring of AD (SCORing Atopic Dermatitis [SCORAD]). RESULTS: Data analysis showed
      no statistical difference for the basal serum cortisol levels (p = .383) and the
      TAI-C (p = .730) between the two groups. No significant correlation was found
      between the basal cortisol values and the TAI-C scores in the AD group (p =
      .290). The SCORAD index was correlated with the TAI-C scores (p < .05) but not
      correlated with the basal serum cortisol values in AD patients (p = .06).
      CONCLUSION: Children with AD do not have more anxiety or different cortisol
      levels when compared with normal children, but the severe symptomatology of AD
      itself may cause anxiety levels to increase in children with AD.

PMID- 20128986
TI  - Update on intralesional steroid: focus on dermatoses.
AB  - BACKGROUND: Intralesional steroid (ILS; usually triamcinolone acetonide) is
      commonly used, and the literature contains much information about its use in
      keloids, hemangiomas, and alopecia areata. Little has been written about its use
      in inflammatory dermatoses such as psoriasis and localized dermatitis since the
      1960s, the conditions for which it was originally most studied and used.
      OBJECTIVE: To clarify the use of ILS and to encourage its use in psoriasis and
      localized dermatitis. METHODS: Medline peer-reviewed literature in English (1956
      2008) was searched for the use of ILS in all skin diseases. Six standard
      textbooks of dermatology were reviewed. Information as to how they used ILS was
      obtained from a questionnaire completed by 33 dermatologists and from personal
      discussions with 15 other dermatologists. Additional information was obtained
      from 40 years of personal ILS use and from observation of 42 dermatologists
      working intermittently in our office over the past 25 years. ILS product package
      inserts and company drug monographs were reviewed. RESULTS: ILS is used by most
      dermatologists, but there are considerable divergences in technique and dosing.
      Current textbooks contain little on its use in psoriasis and localized
      dermatitis. There have been no clinical studies since the 1960s, and their end
      points and descriptions were somewhat vague by today's standards. Product package
      inserts are dated and not helpful. Nevertheless, the use of ILS is safe and
      economical, and the original authors and our office have found it consistently to
      be virtually 100% effective at 2.5 mg/mL in small plaques of psoriasis on the
      trunk and limbs and highly effective in localized dermatitis (such as lichen
      simplex chronicus, prurigo nodularis, and nonspecific eczema). Clinical studies
      indicate that we can safely increase our ILS from the usual 3 cc (7.5 mg) to 6 cc
      (15 mg) or even to 8 cc (20 mg) for patients over 50 kg every 3 to 4 weeks. Serum
      cortisol can be performed if there are concerns about adrenal suppression, with
      use in periorbital hemangiomas and with intranasal ILS. Blindness (from central
      artery occlusion) was reported with injections of ILS around the eyes wih older
      products during the early development stages; and more recently with the use of
      ILS for periorbital hemangiomas and with ILS used intranasally. It has never been
      reported with low pressure injections of ILS using triamcinalone acetonide at 2.5
      mg around the eyes. LIMITATIONS: No formal clinical studies since the 1960s. Poor
      statistical end points. CONCLUSIONS: ILS at 2.5 mg/cc is safe, economical, and
      effective and its greater use should be encouraged in inflammatory dermatoses
      such as psoriasis and localized dermatitis. Further well-designed research would
      be helpful.

PMID- 20128987
TI  - The case for early detection of melanoma.
AB  - BACKGROUND AND OBJECTIVE: The incidence and mortality from melanoma continue to
      rise worldwide. Unfortunately, there is still no consistently effective treatment
      for metastatic disease. The fact that survival for melanoma has increased
      dramatically over the last 30 years highlights the importance of early detection
      of this malignancy. CONCLUSION: With continued public education and the advent of
      new technologies, it is hoped that we will be able to improve on what has been
      accomplished to date to reduce the health burden of melanoma even further. This
      article reviews issues related to patient and physician detection of melanoma and
      highlights newer technologies being used for this purpose.

PMID- 20128988
TI  - Meyerson phenomenon.
AB  - BACKGROUND: Meyerson phenomenon is an uncommon clinical condition that is
      characterized by an eczematous halo surrounding a preexisting melanocytic nevus
      and numerous other lesions. The etiology of this condition is unknown. We suggest
      that the mechanism is due to the interaction between CD4 T lymphocytes and
      increased expression of intercellular cell adhesion molecule 1 (ICAM-1).
      OBJECTIVE: This article provides a concise overview of Meyerson phenomenon.
      METHODS AND RESULTS: We present the case of a 37-year-old female with an inflamed
      nevus located on her thigh from no evident cause. Her condition resolved with
      surgical excision of the nevus. Histopathology of the specimen demonstrated
      spongiosis and lymphocytic infiltrate with eosinophils, which confirmed the
      diagnosis of Meyerson phenomenon. CONCLUSION: Meyerson phenomenon can resolve
      spontaneously or with treatment of either topical steroids or surgical excision.
      The main concern with benign lesions presenting with inflammation is malignant
      transformation; thus, clinicians need to be more aware of Meyerson phenomenon.

PMID- 20128989
TI  - Aphthous vulvar ulcers in adolescent girls: case report and review of the
      literature.
AB  - BACKGROUND: Aphthous vulvar ulcers are painful ulcerations on the genital mucosa
      frequently accompanied by systemic symptoms. They are most commonly reported in
      young women and adolescents without a history of sexual contact. Diagnosis is
      made by exclusion of more common causes, and treatment for this self-limited
      condition is mainly symptomatic. OBJECTIVE: Clinicians should be aware of this
      rare condition to avoid misdiagnoses and unwarranted investigations into sexual
      abuse or false accusations of sexual activity. METHODS: We report a case of an 11
      year-old girl with systemic symptoms and vulvar ulcers of unknown etiology.
      RESULTS: The patient's illness was consistent with previous reports that vulvar
      ulcers can occur without sexual transmission or a documented infectious cause.
      CONCLUSION: A lack of general knowledge regarding this entity may lead to its
      exclusion from the differential diagnosis of vulvar ulcers in this patient
      population. Aphthous ulcers should be strongly considered in any adolescent with
      vulvar ulcers.

PMID- 20128990
TI  - Elastosis perforans serpignosa: treatment with liquid nitrogen cryotherapy and
      review of the literature.
AB  - BACKGROUND: Elastosis perforans serpiginosa (EPS) is a rare skin disease in which
      abnormal elastic tissue fibers, other connective tissue elements, and cellular
      debris are expelled from the papillary dermis via transepithelial elimination. It
      is characterized by an eruption of small grouped hyperkeratotic papules in a
      serpiginous arrangement. This condition presents a therapeutic challenge as many
      treatments have been reported with inconsistent efficacy. METHODS: This article
      reports a case of a 13-year-old male who presented to our outpatient clinic with
      a 1-year history of facial lesions showing multiple annular keratotic plaques
      with slight central atrophy. CONCLUSION: We report a case of EPS treated
      successfully with liquid nitrogen cryotherapy. Liquid nitrogen cryotherapy is
      well tolerated, with few side effects, and can be considered in the management of
      EPS.

PMID- 20128991
TI  - Tonsil metastasis from cutaneous melanoma: first clinical sign of recurrence
      after complete lymph node dissection.
AB  - BACKGROUND: The development of melanoma metastasis to the palatine tonsil is a
      very rare event, generally associated with advanced-stage disease and poor
      prognosis. CASE PRESENTATION: A 29-year-old man presented with a melanoma
      metastasis to the right palatine tonsil 6 months after the surgical excision of
      an ulcerated nodular melanoma (tumor thickness 1.8 mm, Clark level IV) on the
      left shoulder. A metastatic sentinel lymph node had been removed from the left
      axilla, and a subsequent complete lymph node dissection had disclosed no further
      metastatic lymph nodes. Although staging tests had revealed multiple visceral
      metastases, a palliative tonsillectomy was performed. The patient died of
      metastases 5 months later. CONCLUSION: The case presentation suggests that
      careful examination of the head and neck should be part of the routine follow-up
      visit in all melanoma patients.

PMID- 20128992
TI  - Targetoid lesions and neutrophilic dermatosis within neonatal lupus
      erythematosus: unusual clinical and histologic presentations.

PMID- 20128993
TI  - Keratoacanthoma centrifugum marginatum: a rare variant of keratoacanthoma.

PMID- 20128994
TI  - Unconventional nuclides for radiopharmaceuticals.
AB  - Rapid and widespread growth in the use of nuclear medicine for both diagnosis and
      therapy of disease has been the driving force behind burgeoning research
      interests in the design of novel radiopharmaceuticals. Until recently, the
      majority of clinical and basic science research has focused on the development of
      11C-, 13N-, 15O-, and 18F-radiopharmaceuticals for use with positron emission
      tomography (PET) and 99mTc-labeled agents for use with single-photon emission
      computed tomography (SPECT). With the increased availability of small, low-energy
      cyclotrons and improvements in both cyclotron targetry and purification
      chemistries, the use of "nonstandard" radionuclides is becoming more prevalent.
      This brief review describes the physical characteristics of 60 radionuclides,
      including beta+, beta-, gamma-ray, and alpha-particle emitters, which have the
      potential for use in the design and synthesis of the next generation of
      diagnostic and/or radiotherapeutic drugs. As the decay processes of many of the
      radionuclides described herein involve emission of high-energy gamma-rays,
      relevant shielding and radiation safety issues are also considered. In
      particular, the properties and safety considerations associated with the
      increasingly prevalent PET nuclides 64Cu, 68Ga, 86Y, 89Zr, and 124I are
      discussed.

PMID- 20128995
TI  - Optical imaging of integrin alphavbeta3 expression with near-infrared fluorescent
      RGD dimer with tetra(ethylene glycol) linkers.
AB  - Integrin alphavbeta3 plays great roles in tumor angiogenesis, invasion, and
      metastasis. We report here the noninvasive visualization of tumor integrin
      alphavbeta3 expression by using near-infrared fluorescence (NIRF) imaging of an
      IRDye800-labeled new cyclic RGD (arginine-glycine-aspartic acid) dimer with
      tetra(ethylene glycol) (PEG4) linkers (ie, E[PEG4-c(RGDfK)]2, PEG4 = 15-amino
      4,7,10,13-tetraoxapentadecanoic acid) in a U87MG tumor model. Fluorescent dye
      labeled E[PEG4-c(RGDfK)]2 were subjected to in vitro cell staining, in vivo NIRF
      imaging, ex vivo NIRF imaging, and histologic studies. The in vitro and in vivo
      characterization of dye-labeled E[PEG4-c(RGDfK)]2 were compared with dye-labeled
      RGD dimer without PEG4 linkers (namely, E[c(RGDfK)]2). Both Cy5.5-E[PEG4
      c(RGDfK)]2 and Cy5.5-E[c(RGDfK)]2 exhibited integrin alphavbeta3 binding
      specificity in a cell-staining experiment. In vivo NIRF imaging showed higher
      tumor accumulation and tumor to background contrast of IRDye800-E[PEG4-c(RGDfK)]2
      over IRDye800-E[c(RGDfK)]2. The tumor integrin alphavbeta3 specificity of
      IRDye800-E[PEG4-c(RGDfK)]2 was confirmed by successful inhibition of tumor uptake
      in the presence of an excess dose of c(RGDfK). Histologic examination revealed
      both tumor vasculature and tumor cell integrin alphavbeta3 binding of IRDye800
      E[PEG4-c(RGDfK)]2 in vivo. In summary, NIRF imaging with IRDye800-E[PEG4
      c(RGDfK)]2 offers an easy, fast, and low-cost way to detect and semiquantify
      tumor integrin alphavbeta3 expression in living subjects.

PMID- 20128996
TI  - Quantitative assessment of intestinal injury using a novel in vivo, near-infrared
      imaging technique.
AB  - Intestinal injury owing to inflammation, severe trauma, and burn is a leading
      cause of morbidity and mortality. Currently, animal models employed to study the
      intestinal response to injury and inflammation depend on outdated methods of
      analysis. Given that these classic intestinal assays are lethal to the
      experimental animal, there is no ability to study the gut response to injury in
      the same animal over time. We postulated that by developing an in vivo assay to
      image intestinal injury using fluorescent dye, it could complement other
      expensive, time-consuming, and semiquantitative classic means of detecting
      intestinal injury. We describe a novel in vivo, noninvasive method to image
      intestinal injury using a charge-coupled device (CCD) camera that allows for
      serial visual and quantitative analysis of intestinal injury. Our results
      correlate with traditional, time-consuming, semiquantitative assays of intestinal
      injury, now allowing the noninvasive, nonlethal assessment of injury over time.

PMID- 20128997
TI  - Patient-tailored, imaging-guided, long-term temozolomide chemotherapy in patients
      with glioblastoma.
AB  - We present two patients with glioblastoma with an unusually stable clinical
      course and long-term survival who were treated after surgery and radiotherapy
      with adjuvant temozolomide (TMZ) chemotherapy for 17 and 20 cycles, respectively.
      Afterward, adjuvant TMZ chemotherapy was discontinued in one patient and the
      dosage of TMZ was reduced in the other. In addition to clinical status and
      magnetic resonance imaging, the biologic activity of the tumors was monitored by
      repeated methyl-11C-l-methionine (MET) and 3'-deoxy-3'-18F-fluorothymidine (FLT)
      positron emission tomography (PET) studies in these patients. In these patients,
      repeated MET- and FLT-PET imaging documented complete response to the initial
      treatment regimen, including resection, radiation, and TMZ, and during the course
      of the disease, recurrent, uncontrollable tumor activity. Continuation or dose
      escalation of TMZ in both patients was shown to be ineffective to overcome the
      metabolic activity of the tumor. Our data suggest that repeated MET- and FLT-PET
      imaging provide information on the biologic activity of a tumor that is highly
      useful to monitor and detect changes in activity.

PMID- 20128998
TI  - Different strategies for reducing intestinal background radioactivity associated
      with imaging HSV1-tk expression using established radionucleoside probes.
AB  - One limitation of HSV1-tk reporter positron emission tomography (PET) with
      nucleoside analogues is the high background radioactivity in the intestine. We
      hypothesized that endogenous expression of thymidine kinase in bacterial flora
      could phosphorylate and trap such radiotracers, contributing to the high
      radioactivity levels in the bowel, and therefore explored different strategies to
      increase fecal elimination of radiotracer. Intestinal radioactivity was assessed
      by in vivo microPET imaging and ex vivo tissue sampling following intravenous
      injection of 18F-FEAU, 124I-FIAU, or 18F-FHBG in a germ-free mouse strain. We
      also explored the use of an osmotic laxative agent and/or a 100% enzymatically
      hydrolyzed liquid diet. No significant differences in intestinal radioactivity
      were observed between germ-free and normal mice. 18F-FHBG-derived intestinal
      radioactivity levels were higher than those of 18F-FEAU and 124I-FIAU; the
      intestine to blood ratio was more than 20-fold higher for 18F-FHBG than for 18F
      FEAU and 124I-FIAU. The combination of Peptamen and Nulytely lowered intestinal
      radioactivity levels and increased (2.2-fold) the HSV1-tk transduced xenograft to
      intestine ratio for 18F-FEAU. Intestinal bacteria in germ-free mice do not
      contribute to the high intestinal levels of radioactivity following injection of
      radionucleoside analogues. The combination of Peptamen and Nulytely increased
      radiotracer elimination by increasing bowel motility without inducing
      dehydration.

PMID- 20128999
TI  - Diagnosis, treatment, and recovery maintenance in bipolar depression.
AB  - Misdiagnosis of bipolar disorder and inappropriate pharmacotherapeutic treatment
      is common. Clinicians should screen for manic/hypomanic symptoms during
      depressive episodes to differentiate bipolar depression from other depressive
      disorders. Depression is the dominant pole of bipolar disorder, and effective
      maintenance therapy must prevent depressive episode recurrence. Few pharmacologic
      treatments have evidence supporting both short- and long-term efficacy for
      bipolar depression. Clinicians must consider the existing evidence on the long
      term efficacy of various pharmacologic and psychosocial interventions for
      preventing and treating bipolar mood episodes.

PMID- 20129000
TI  - Depression symptomatology and neurobiology.
AB  - The DSM-IV-TR distinguishes major depressive disorder (MDD) from normal sadness
      and grief by requiring a certain duration and number of symptoms that cause
      impairment and dysfunction. Depression is considered a heterogeneous condition in
      which different biologic abnormalities may be responsible for problems with
      sleeping, eating, energy, and emotional reactions. Neuroimaging, pharmacology,
      and genomics are among the sources of information that have contributed to
      theories about the pathophysiology of MDD and may lead to truly personalized
      medicine in the future.

PMID- 20129001
TI  - Pharmacotherapy and other treatments for elderly patients with depression.
AB  - Depression in older adults can be difficult to diagnose and a challenge to treat.
      Clinicians must address treatment issues caused by aging, such as comorbid
      medical illness, physical limitations, or the presence of cognitive impairments.
      Proven treatments for depression in older adults include psychotherapy,
      medications, and electroconvulsive therapy. When choosing therapies for older
      patients, possible adverse side effects, drug interactions, and patient
      limitations should guide treatment selection.

PMID- 20129003
TI  - Mechanism of action of stimulants in attention-deficit/hyperactivity disorder.

PMID- 20129004
TI  - The prevalence of personality disorders in hypochondriasis.
AB  - BACKGROUND: Although Axis I hypochondriasis is closely related to certain
      personality characteristics, the nature and extent of personality dysfunction in
      these patients still needs clarification. This study assessed the prevalence of
      personality disorders observed in hypochondriacal patients, described the types
      and comorbidity of personality disorders, and compared the psychological distress
      of patients with and without the most common comorbid personality disorder.
      METHOD: One hundred fifteen patients meeting Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, criteria for hypochondriasis completed self
      administered assessments, including the Personality Diagnostic Questionnaire-4+
      (PDQ-4+), the Hopkins Symptom Checklist-90-Revised (SCL-90-R), the Whiteley
      Index, and the Somatic Symptom Inventory. These data were taken from a study
      conducted between September 1997 and November 2001. RESULTS: Eighty-eight
      patients (76.5%) had 1 or more personality disorders, whereas 27 patients (23.5%)
      had no personality disorders. Fifty-one patients (44.3%) had more than 3
      personality disorders. The most common personality disorder in the
      hypochondriacal patients was obsessive-compulsive personality disorder (OCPD;
      55.7%), followed by avoidant personality disorder (40.9%). The comorbidity of
      OCPD and avoidant personality disorder was 53.1% (34 of 64 patients with OCPD).
      The total PDQ-4+ score of the 64 patients with OCPD was significantly higher than
      that of the 51 patients without OCPD. On the SCL-90-R, the 64 patients with OCPD
      showed significantly higher scores on all of 3 global indices and 7 of 10 primary
      symptom dimensions (paranoid ideation, depression, anxiety, phobic anxiety,
      obsessive-compulsive, interpersonal sensitivity, and psychoticism) on the SCL-90
      R compared to the 51 patients without OCPD. CONCLUSIONS: The high prevalence of
      personality disorders, particularly OCPD, among patients with hypochondriasis
      suggests that consideration of personality features is important in assessment
      and therapeutic interventions for hypochondriasis.

PMID- 20129005
TI  - Bipolar symptoms in adult attention-deficit/hyperactivity disorder: a cross
      sectional study of 510 clinically diagnosed patients and 417 population-based
      controls.
AB  - OBJECTIVE: Bipolar spectrum disorders (BSD) have several symptoms and features in
      common with attention-deficit/hyperactivity disorder (ADHD). Here we explored the
      prevalence of BSD and the relationship between symptoms of BSD and ADHD in adult
      ADHD patients. METHOD: Norwegian adults diagnosed with DSM-IV ADHD during 1997
      through 2007 (n = 510) and a random sample of 417 controls from the general
      population (aged 18-40 years) were recruited and responded to 85 questions rating
      symptoms of ADHD, lifetime symptoms of mood disorders, other comorbid conditions,
      and sociodemographic data. RESULTS: According to the Mood Disorder Questionnaire
      (MDQ), 50.6% of the ADHD patients screened positive for BSD, compared to 8.3% of
      the controls. In comparison, the prevalence of BSD according to DSM-IV in a
      subsample of interviewed patients (n = 50) was 32%. In the whole study sample (N
      = 927), an ADHD diagnosis was the strongest predictor for screening positive on
      the MDQ (OR = 5.0, P < .001), but the correlation between dimensional symptom
      levels of ADHD and of BSD was strongest in the control group (Pearson correlation
      r = 0.7, P < .001 vs r = 0.3, P < .001). Patients screening positive on the MDQ
      had significantly more drug problems, higher ADHD symptom scores, and lower
      educational and occupational levels. CONCLUSIONS: Our findings illustrate the
      close relationship between some symptoms of BSD and ADHD in adults. In clinical
      and research settings, patients screening positive for BSD should be assessed for
      a possible underlying or coexisting ADHD condition and vice versa.

PMID- 20129006
TI  - Cognizance of cognition in older primary care patients with depression and
      restraining restraint and agitation in nursing home residents with dementia.

PMID- 20129007
TI  - Depression predicts cognitive disorders in older primary care patients.
AB  - OBJECTIVE: To investigate whether depression is independently associated with
      increased risk of incident dementia or cognitive disorder not otherwise specified
      (NOS) in an older primary care population. METHOD: This was a prospective 3-year
      cohort study of 470 patients aged >or= 65 years without baseline cognitive
      disorders who were recruited from primary care offices. Annual assessments
      completed from March 2003 through December 2005 included the use of the
      Structured Clinical Interview for DSM-IV to diagnose major depressive disorder
      (MDD) and minor depression (MinD) and the Hamilton Depression Rating Scale (HDRS)
      for depressive symptom severity. The Mini-Mental State Exam, Mattis Dementia
      Rating Scale-initiation/perseveration subscale, and the Trail Making Tests A and
      B informed diagnoses of dementia and cognitive disorder NOS. RESULTS: 36
      subjects, representing a cumulative incidence of 13%, developed dementia or
      cognitive disorder NOS over 3 years. Using Cox proportional hazard survival
      models to calculate the risk ratio of depression for development of cognitive
      disorders, MDD and MinD (HR = 3.68; 95% CI, 2.1-6.42 and HR = 1.84; 95% CI, 1.05
      3.21, respectively) and HDRS scores (HR = 1.07; 95% CI, 1.02-1.12) predicted new
      onset dementia or cognitive disorder NOS, when covarying age, gender, and
      education. CONCLUSIONS: Depressive disorders pose increased risk of incident
      dementia or cognitive disorder NOS in older primary care patients. Clinicians
      treating depressed older adults should monitor for development of cognitive
      disorders.

PMID- 20129008
TI  - The effect of staff training on agitation and use of restraint in nursing home
      residents with dementia: a single-blind, randomized controlled trial.
AB  - INTRODUCTION: Agitation is common in dementia and is associated with use of
      restraints and use of psychotropic drugs. The aim of this study was to determine
      whether an education and supervision intervention could reduce agitation and the
      use of restraints and antipsychotic drugs in nursing homes. METHOD: Four
      Norwegian nursing homes were randomly allocated to receive either treatment as
      usual or an intervention consisting of a 2-day educational seminar and monthly
      group guidance for 6 months. One hundred forty-five residents with dementia
      (based on medical records and corroborated with a Functional Assessment Staging
      score >or= 4) completed baseline and 6-month intervention assessments and were
      included in the analyses. The co-primary outcome measures were the proportion of
      residents subject to interactional restraint and the severity of agitation using
      the Cohen-Mansfield Agitation Inventory (CMAI). Patients were assessed at
      baseline, immediately after completion of the intervention at 6 months, and 12
      months after baseline. Comparison of change in the 2 groups was made using
      repeated-measures analysis of variance (CMAI) and Mann-Whitney test (restraints).
      The study was conducted from 2003 to 2004. RESULTS: The proportion of residents
      starting new restraint was lower in the intervention than in the control group at
      6-month evaluation (P = .02), but no statistically significant differences were
      found at 12-month assessment (P = .57). The total CMAI score declined from
      baseline to 6 and 12 months' follow-up in the intervention homes compared to a
      small increase in the control homes (F2,176 = 3.46, P = .034). There were no
      statistically significant differences in use of antipsychotic drugs. CONCLUSIONS:
      A brief 2-day staff education program followed by continued monthly guidance was
      able both to improve quality of care by reducing the frequency of interactional
      restraints and to reduce severity of agitation.

PMID- 20129009
TI  - Olfactory reference syndrome as a subtype of body dysmorphic disorder.

PMID- 20129010
TI  - Dosing by side effect threshold: two cases of panic disorder responsive to low
      dose venlafaxine.

PMID- 20129011
TI  - Lack of association between serum brain-derived neurotrophic factor levels and
      improvement of schizophrenia symptoms in a double-blind, randomized, placebo
      controlled trial of memantine as adjunctive therapy to clozapine.

PMID- 20129012
TI  - Command hallucinations with self-stabbing associated with zolpidem overdose.

PMID- 20129014
TI  - Diabetic kidney disease: act now or pay later.

PMID- 20129015
TI  - Relative hypoparathyroidism and hypoalbuminemia are associated with hip fracture
      in hemodialysis patients.
AB  - AIMS: Patients with end-stage renal disease treated by hemodialysis are at an
      increased risk of hip fracture. In the general population, hip fractures are
      associated with increased morbidity and mortality. The objective of this study
      was to assess the predictors and outcomes of hip fracture in the hemodialysis
      population, including quality of life post hip fracture. METHODS: A case-control
      study from 1999 to 2005 included 29 adult hemodialysis patients with hip fracture
      and 55 controls, matched on age, gender and number of years on hemodialysis. A
      logistic regression model was used to derive predictors of hip fracture. The
      association between time to death post hip fracture and parathyroid hormone was
      analyzed using a Kaplan-Meier curve. The ability to live independently 1 year
      after hip fracture was used as a measure of quality of life. RESULTS: Variables
      associated with hip fracture were a reduction in serum parathyroid hormone by 100
      pg/ml (OR = 1.65, 95% CI 1.10, 2.46) and a decrease in serum albumin by 1 g/l (OR
      = 1.18, 95% CI 1.00, 1.39). 40% of the cases died within the first year post hip
      fracture. Median survival time in patients with hip fracture and a serum PTH
      value < 100 pg/ml was 17 days (95% CI 0, 37 days) as compared with 280 days (95%
      CI 103, 471 days) for those with a PTH value > 100 pg/ml (p < 0.02). Among the
      patients who survived, 53% were subsequently discharged to a long-term care
      facility. CONCLUSIONS: Relative hypoparathyroidism and hypoalbuminemia are
      associated with an increased risk of hip fracture in hemodialysis patients. There
      is also a significant reduction in quality of life in patients sustaining a hip
      fracture.

PMID- 20129016
TI  - C.E.R.A. safety profile: a pooled analysis in patients with chronic kidney
      disease.
AB  - BACKGROUND: C.E.R.A., a continuous erythropoietin receptor activator, is a long
      acting erythropoiesis-stimulating agent (ESA) that is approved for the treatment
      of renal anemia. This analysis evaluated the safety profile of C.E.R.A. in
      comparison to that of other ESAs in patients with chronic kidney disease (CKD).
      METHODS: Safety parameters were analyzed in a pooled population comprising all
      patients with CKD on dialysis and not on dialysis from the completed Phase II and
      Phase III studies in the C.E.R.A. clinical program (Phase II/III population);
      patients were treated with either C.E.R.A. (n = 1,789) or comparator ESA (n =
      948). Differences between treatment groups in safety parameters were identified
      by either a 2% difference in incidence between groups, or a statistically
      significant difference between groups (p < or = 0.05 with the Fisher's exact
      test, which was used as a conservative screening tool). To assess changes in
      safety findings over time, long-term safety data were analyzed from patients who
      were given the option to enter long-term safety studies upon completing their
      initial Phase II/III study (safety extension population). RESULTS: Compared with
      the C.E.R.A. group, the incidence of adverse events (AEs) was higher in the
      comparator ESA group in the Phase II/III population (C.E.R.A. vs. comparator ESA,
      89.5% vs. 91.8%, p = 0.067), and significantly so in the safety extension
      population (93.0% vs. 95.8%, p = 0.003). The incidence of serious AEs was
      significantly higher in the comparator ESA group than in the C.E.R.A. group in
      both analysis populations (Phase II/III population, 37.8% vs. 42.4%, p = 0.021;
      safety extension population, 53.3% vs. 59.7%, p = 0.001). However, there was no
      consistent pattern of clinical events that could explain these differences
      between the treatment groups. CONCLUSION: Analysis of safety events in patients
      with renal anemia receiving long-term treatment with C.E.R.A. shows a safety
      profile comparable to that of other ESAs.

PMID- 20129017
TI  - Significance of self-reported sleep quality (SQ) in chronic kidney disease (CKD):
      the Renal Research Institute (RRI)-CKD study.
AB  - BACKGROUND: There has been limited research on sleep quality (SQ) in CKD.
      METHODS: This prospective cohort study of adults with CKD Stages 3 - 5 at four US
      centers collected self-reported SQ information from the Kidney Disease Quality of
      Life (KDQOL) instrument, including an estimated SQ score (0 - 100), and 3 SQ
      related questions. "Poor" SQ was defined as SQ score < or = 60. Logistic and
      multiple linear regression assessed associations between SQ and its potential
      predictors. Times to death and end stage renal disease (ESRD) were examined using
      Cox regression. A comparison with SQ in ESRD patients from the Dialysis Outcomes
      and Practice Patterns Study (DOPPS), was additionally performed. RESULTS: Mean SQ
      score was 59.4 +/- 23.6 (n = 689), and "poor" SQ was reported by 57%. Mean
      estimated glomerular filtration rate (eGFR) was 24.9 +/- 10.6 ml/min/1.73 m2.
      Higher SQ significantly correlated with KDQOL mental and physical component
      summary scales. Significant predictors of lower SQ score included--younger age,
      presence of dyspnea, self-reported depression, pain, and itchness. There were no
      significant pairwise differences in SQ from CKD Stage 3 through ESRD. Self
      reported daytime sleepiness was significantly associated with higher risk of
      mortality prior to ESRD (HR = 1.85, p = 0.02). CONCLUSION: Self-reported "poor"
      SQ was common in a CKD cohort (Stages 3 - 5) and was not only associated with
      lower quality of life scores and several modifiable symptoms, but also with
      higher risk of pre-ESRD mortality. Greater attention to this clinical problem is
      highly recommended in this high-risk population.

PMID- 20129018
TI  - Familial IgA nephropathy in southeastern Kentucky.
AB  - BACKGROUND: Two decades ago, pedigrees of patients with IgA nephropathy (IgAN)
      from Pike County, KY, USA, provided evidence for a role of genetic factors in the
      pathogenesis of this disorder. Subsequently additional pedigrees were described
      for several communities from northern Italy. Recently, we found another cluster
      of patients in the Clay County, KY area, about 100 miles southwest of Pike
      County. AIM: The purpose of this study was to evaluate and expand the pedigrees
      of patients with IgAN from Clay County, KY to provide additional insight into the
      mechanisms of inheritance of IgAN and assess the possible influence of a founder
      effect on the prevalence of IgAN in the region. METHOD: Since 1980, most patients
      with IgAN and their relatives in eastern KY have provided personal genealogic
      data. These data were used to construct pedigrees that included the patients born
      in Clay County. Nine of 11 patients with IgAN born in Clay County, KY, USA were
      members of 1 or more of 5 pedigrees, each with 3 - 11 patients with IgAN.
      CONCLUSION: Our findings suggest the possibility of a low-penetrance ancestral
      mutation in the IgAN kindreds from Clay County.

PMID- 20129019
TI  - Individual effect of renin-angiotensin system inhibition and corticosteroid
      therapy in IgA glomerulonephritis: results of a pilot study.
AB  - BACKGROUND: The impact of different therapy modalities on the outcome of
      Immunoglobulin A glomerulonephritis (IgAGN) in individual patient is not clear.
      We present preliminary results from the sequential application of renin
      angiotensin system (RAS) inhibition and corticosteroids to discriminate the
      individual effect of both therapies. METHODS: Regardless of the degree of
      proteinuria, renal function and histological grading, patients with biopsy-proven
      IgAGN were treated with a standardized protocol. RAS inhibition was performed for
      3 months. Thereafter, immunosuppressive therapy with prednisone (0.5 mg/kg body
      weight) on alternate days for 6 months was started. The primary endpoint was a
      maximal reduction of proteinuria (spot urine protein/ creatinine ratio (uPCR)),
      by RAS inhibition and by the combination of RAS inhibition and steroids. RESULTS:
      10 patients were treated according to the protocol. During a median follow-up of
      18 months, uPCR decreased from initial 230 mg/mmol (2 g/g) (median, interquartile
      range (IQR) 146 - 396) to 154 mg/mmol (1.4 g/g) (IQR 88 - 190) at 3 months during
      the RAS inhibition period (33% reduction, p = 0.01) and further to 31 mg/mmol
      (0.3 g/g) (IQR 21 - 71) until end of the steroid period at 9 months (80%
      reduction compared to uPCR at 3 month, p < 0.001). At the last F/U, uPCR (median)
      remained stable at 41 mg/mmol (0.4 g/g). The estimated glomerular filtration rate
      was stable during the whole observation period. CONCLUSIONS: Sequential RAS
      inhibition and steroid treatment leads to a continuous decrease in proteinuria,
      beyond the decrease produced by isolated RAS inhibition. Our data suggest
      independent effects of both, RAS inhibition and steroids, on the reduction of
      proteinuria in a small, non selected group of patients with IgAGN. The hypothesis
      that patients with IgAGN, regardless of the degree of proteinuria, renal function
      and histological grading, may benefit from combination therapy with maximal RAS
      inhibition and low dose corticosteroids now has to be confirmed in a randomized
      study.

PMID- 20129020
TI  - Paraoxonase 1 arylesterase activity and mass are reduced and inversely related to
      C-reactive protein in patients on either standard or home nocturnal hemodialysis.
AB  - Human serum paraoxonase (PON1) activity is reduced in standard hemodialysis (SHD)
      (4 hours, 3 days/week) patients. Home nocturnal hemodialysis (HNHD) (8 hours, 6
      days/week), provides a greater dialysis dose resulting in a greater clearance of
      metabolites. Whether improvements in the metabolic milieu of HNHD patients
      results in different PON1 activity levels compared to SHD patients is unclear. We
      determined serum PON1 mass and arylesterase activities in a group of HNHD
      patients and compared them to SHD patients and a group of healthy controls (HC).
      PATIENTS AND METHODS: We measured PON1 arylesterase activity and mass, C-reactive
      protein (CRP), cystatin C, total and high-density lipoprotein (HDL) cholesterol,
      triglycerides, apolipoproteins A-I and B in 15 HNHD, 15 SHD and 15 HC
      participants. RESULTS: PON1 arylesterase activity (p < 0.001) and mass (p < 0.05)
      were significantly higher in HC participants compared to SHD and HNHD
      participants, although no significant differences were noted between HD groups.
      CRP (p < 0.05) was significantly higher in SHD compared to HC participants and
      there were no significant differences noted between HD groups. Cystatin C (p <
      0.001) was significantly different among the 3 groups. There were no significant
      differences noted in any lipoprotein parameters among the groups. PON1 activity
      (r = -0.636, p < 0.001) and mass (r = -0.425, p = 0.019) were inversely
      correlated with CRP in HD patients. CONCLUSION: PON1 is reduced in HNHD patients
      compared to HC subjects, independent of the concentration of HDL cholesterol.
      Within subjects on HD, the combination of increased CRP and reduced PON1 may
      identify subjects at a high risk for cardiovascular complications.

PMID- 20129021
TI  - Renoprotective effects of telmisartan in patients with advanced chronic kidney
      disease.
AB  - BACKGROUND: Angiotensin II receptor blockers (ARBs) provide renoprotective
      effects in patients with mild-to-moderate chronic kidney disease (CKD). However,
      there have been few reports regarding whether ARBs show clinical efficacy and
      safety in patients with advanced CKD. METHODS: Seventy-two hypertensive patients
      with Stages 3 - 4 CKD receiving no ARBs were enrolled in this study and observed
      up to 48 months. Telmisartan was added to conventional antihypertensive agents (n
      = 36, mean estimated glomerular filtration ratio [eGFR] 19.7 ml/min/1.73 m2)
      whilst the remaining control patients were not treated with ARBs (n = 36, mean
      eGFR 19.2 ml/min/1.73 m2). Urinary protein excretion, kidney function, and the
      occurrence of end-stage renal disease requiring renal replacement therapy,
      hyperkalemia, and death were analyzed. RESULTS: Baseline characteristics of each
      group were similar. During the observation period, the blood pressures of each
      group decreased at similar rates. In the telmisartan group, 17 patients (47.2%)
      were introduced to renal replacement therapy, as compared with 31 patients
      (86.1%) in the control group (relative risk 0.55, 95% confidence interval 0.19 -
      0.92, p < 0.05). Telmisartan significantly reduced proteinuria levels (from 3.47
      +/- 3.00 to 2.41 +/- 2.46 g/g . creatinine, p < 0.05) and was associated with a
      reduction of 49.6% in the decline rate of eGFR. The incidence of major adverse
      events in both groups was similar. CONCLUSIONS: The addition of telmisartan to
      conventional antihypertensive therapy is associated with significant improvement
      in kidney outcome without increased incidence of adverse effects, even in
      patients with advanced CKD.

PMID- 20129022
TI  - Severe renal failure and microangiopathic hemolysis induced by malignant
      hypertension--case series and review of literature.
AB  - Malignant nephrosclerosis is acute renal failure in the setting of malignant
      hypertension and may be associated with thrombotic microangiopathy. Although the
      prognosis has improved considerably over the past decades, renal dysfunction
      remains an important cause of morbidity and mortality. Adequate control of blood
      pressure is crucial, allows gradual healing of the necrotizing vascular lesions
      and may induce stabilization and improvement of renal function in about 50 - 80%
      of involved patients. In addition, recent investigations have provided a better
      understanding of the pathophysiology of malignant hypertension and offer
      possibilities for identifying patients at risk. We report 3 patients who
      developed severe acute renal failure requiring dialysis initiation in the setting
      of malignant hypertension. All patients had kidney biopsy proven malignant
      nephrosclerosis and presented with symptoms of thrombotic microangiopathy.
      Despite adequate blood pressure control the prognosis of our patients varied.

PMID- 20129023
TI  - Computed tomographic peritoneography in the investigation of patent processus
      vaginalis in CAPD patients.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) is a useful and practical
      modality for the treatment of end-stage renal disease (ESRD). In the properly
      selected patient this method is well-tolerated with minimal complications. We
      report a case of intermittent massive genital edema secondary to patent processus
      vaginalis in a patient receiving CAPD. The diagnosis of patent processus
      vaginalis, which was strongly suggested by the intermittent nature of the
      symptoms, was confirmed by computerized tomography (CT) peritoneography.

PMID- 20129024
TI  - Type B insulin resistance syndrome with systemic lupus erythematosus.
AB  - Type B insulin resistance syndrome is a rare disease. Auto-antibodies to the
      insulin receptor frequently appear in the case of systemic lupus erythematosus
      (SLE). We report herein a case of a 56-year-old man who had presented discoid
      skin lesions since 1990. He was admitted to the hospital because of
      unconsciousness and severe hypoglycemia in 2006, and was diagnosed as having Type
      B insulin resistance syndrome with the presence of insulin receptor antibody. He
      had frequently repeated hypoglycemic and hyperglycemic episodes in spite of
      treatment with prednisolone (5 - 10 mg/day), and mild proteinuria of 1.5 g/day
      was observed. His laboratory findings on admission revealed pancytopenia and
      positive titer for antinuclear antibody (ANA). From these findings and his past
      history of skin lesions, we diagnosed him as SLE. We performed renal biopsy and
      his histological diagnosis was lupus nephritis Class 5 with the findings of
      podocytic shedding. Prednisolone dosage was increased from 10 to 60 mg/day.
      Thereafter, his glucose metabolism improved and proteinuria disappeared. The dose
      of prednisolone was tapered to 30 mg/day without recurrence of hypoglycemia and
      proteinuria. Early treatment with prednisolone might ameliorate proteinuria and
      insulin resistance. We experienced a rare case of Type B insulin resistance
      syndrome with increased activity of SLE, complicated with lupus nephritis. It
      appears that Type B insulin resistance syndrome should be suspected in
      differential diagnosis of hypoglycemia in SLE patients.

PMID- 20129025
TI  - Large perinephric abscess in a patient on maintenance hemodialysis diagnosed by
      positron emission tomography combined with computed tomography (PET-CT).
AB  - Perinephric abscesses in patients on maintenance hemodialysis (HD) have seldom
      been reported. The case of a maintenance HD patient with a left perinephric
      abscess is reported. Although the lesion could not be visualized using other
      imaging examinations, using FDG and positron emission tomography combined with
      computed tomography (PET-CT), the patient was diagnosed as having a left
      perinephric abscess and nephrolithiasis. At the patient's request, the
      perinephric abscess was treated conservatively with antibiotic therapy alone, and
      it eventually remitted. This is the first case report of a perinephric abscess
      diagnosed by FDG PET-CT in a patient on maintenance HD. FDG PET-CT appears to be
      useful for identifying perinephric abscesses in HD patients, resulting in early
      diagnosis and appropriate therapy for this severe infection.

PMID- 20129026
TI  - Successful treatment of membranoproliferative glomerulonephritis associated with
      hepatitis B and C virus simultaneous infection patient.

PMID- 20129027
TI  - Contrast-induced ultrasonography with Levovist in a case of exercise-induced
      acute kidney injury without rhabdomyolysis.

PMID- 20129028
TI  - Intake of sweet drinks and sweet treats versus reported and observed caries
      experience.
AB  - AIM: This was to study the intakes of sweet drinks and sweet treats of children
      and their caries risk using the Paediatric Risk Assessment Tool (PRAT, 2003) and
      Caries-risk Assessment Tool (CAT, 2007-8). STUDY DESIGN: Parents of 266 healthy
      primary school children completed the PRAT questionnaire during their child's
      dental appointment at the Royal Dental Hospital of Melbourne, Australia,
      describing their fluid and sweet treat intakes in the past 24 hours, oral hygiene
      practices and past caries. A subgroup (n=100) was examined clinically (CAT) for
      caries requiring restoration, visible plaque, gingivitis, orthodontic appliances,
      enamel defects, and use of dental care. RESULTS: The estimated mean daily fluid
      intake was 1.5+/-0.5L; fluids were consumed 3-5/ day by 57% of children and 78%
      usually had evening/night drinks. Fluids consumed were: tap water by 90%, milk by
      74%, juice by 50%, regular soft drink by 30%; sweet treats were consumed by 62%
      and confectionery by 25%. Most children (69%) brushed their teeth > or =2/day; 5%
      flossed daily. Parentally-reported caries was associated significantly with
      increasing treats frequency (p=0.006). In the subgroup, 81% were at high caries
      risk; 47% had irregular dental care; 21% had sweet drinks/foods frequently
      between meals; 49% had visible plaque/gingivitis, and 34% had enamel
      demineralisation. Caries observed in the past 12 months was associated
      significantly with evening sweet drinks (p=0.004), and suboptimal fluoride
      exposure (p=0.009). Caries observed in the past 24 months was associated
      significantly with treats frequency (p=0.006), intake of sweet drinks plus treats
      (p=0.000), enamel demineralisation (p=0.000) and irregular dental care (p=0.000).
      CONCLUSIONS: The PRAT and CAT are valuable tools in assessing children's caries
      risk. The risk of caries from frequent intake of sweet drinks, either alone or in
      addition to sweet treats, must be emphasised to parents. All parents, and
      particularly those of children assessed at high risk from intakes of sweet drinks
      and sweet treats, suboptimal fluoride exposure, or enamel demineralisation, must
      be encouraged to obtain regular dental care for their children.

PMID- 20129029
TI  - Resin-modified glass-ionomer cements versus resin-based materials as fissure
      sealants: a meta-analysis of clinical trials.
AB  - AIM: To appraise quantitatively current evidence regarding the caries-preventing
      effect of resin-modified glass-ionomer cement (RM-GIC) fissure sealants in
      comparison to that of resin-based fissure sealants. STUDY DESIGN: Systematic
      review with meta-analysis. METHODS: 8 Anglophone databases and 2 Lusophone
      databases were searched until 15 April 2009, using a pre-determined search
      strategy. Clinical trials were considered for inclusion if their titles/abstracts
      were relevant to the topic, published in English, Portuguese or Spanish and had a
      two-arm longitudinal study design. The outcome measure of the caries-preventive
      effect was caries absence on sealed teeth. Two reviewers independently extracted
      data from the accepted articles in order to complete a 2x2 table for meta
      analysis. The unit of interest was the tooth, and the number of caries-free teeth
      (n) at the end of each time interval (6, 12 and 24 months) was compared against
      the total number of evaluated teeth (N). STATISTICS: Datasets were assessed for
      their clinical and methodological heterogeneity, following Cochrane guidelines,
      and only homogeneous datasets were combined for meta-analysis, using a random
      effects model (RevMan 4.2). Differences in the caries-preventive effect were
      computed on the basis of the combined Relative Risk (RR) with 95% confidence
      interval (CI). RESULTS: Of the 212 articles identified, only 6 trials were
      included. From these, 19 separate datasets were extracted. For the pooled data,
      equivalent caries-preventive effects were observed at 6 months (RR= 0.98, 95% CI
      0.95- 1.00; p = 0.08); 12 months (RR=1.00, 95% CI 0.96-1.04, p = 0.99) and 24
      months (RR=1.01, 95% CI 0.84-1.21, p = 0.91). The 36-month data (not pooled)
      favoured resin-based sealants (RR 0.93, 95% CI 0.88-0.97, p = 0.002).
      CONCLUSIONS: This meta-analysis found no conclusive evidence that either material
      was superior to the other in preventing dental caries.

PMID- 20129030
TI  - Microleakage of three different sealants on sound and questionable occlusal
      surfaces of permanent molars: an in vitro study.
AB  - AIM: This was to evaluate the microleakage of 3 different sealants, applied on
      sound and questionably carious occlusal surfaces with and without a bonding
      agent. METHODS: A total of 120 human molars were selected, photographed with a
      digital video microscope, and assigned by 3 independent examiners, according to
      the criteria of ICDAS II, in 2 groups of 60 teeth each. Group A: teeth with deep,
      clear, sound occlusal surfaces (ICDAS II, code 0). Group B: teeth with
      questionable occlusal surfaces, having deep, stained pits and fissures with
      probable incipient, but non-cavitated carious lesions (ICDAS II, codes 1 and 2).
      Each group was divided into 2 subgroups of 30 teeth each (bonding or no bonding)
      and then into 3 subgroups of 10 teeth each according to the type of sealant used:
      one conventional (Conseal) and 2 fluoridated (Conseal F and Teethmate F). After
      the application of the bonding agent and the sealant to the appropriate teeth,
      all specimens were subjected to thermal cycling and immersed in a 10% methylene
      blue dye solution for 4 hours. Average and summed microleakage for each sample
      were estimated from dye penetration scores on 3 mesiodistal sections of the tooth
      across the sealed occlusal surface. Non-parametric Friedman's 2-way ANOVA by
      ranks and Conover-Inman pair wise comparisons were used for differences at the
      0.05 level of significance. RESULTS: According to Friedman's 2-way ANOVA by ranks
      analysis, although there were no significant differences between the different
      sealants (chi(2) = 0.048, df = 2, P = .976), there were significant differences
      between the sound and questionably carious occlusal surfaces (chi(2) = 24, df =
      3, P = .000). Conover- Inman pair wise comparisons showed no differences between
      the groups using and not using bonding agents, on sound (SNB-SWB, P = .4561) or
      questionable occlusal surfaces (QNB-QWB, P = .0842). CONCLUSIONS: Sealant
      microleakage on questionably carious occlusal surfaces was statistically
      significantly higher than that of sound occlusal surfaces. Using a bonding agent
      or fluoridated FS did not influence microleakage significantly, either on sound
      or on questionable fissured surfaces.

PMID- 20129031
TI  - Factors affecting preoperative anxiety in children undergoing general anaesthesia
      for dental rehabilitation.
AB  - AIM: The primary aim was to examine anxiety levels, and to identify factors
      affecting preoperative anxiety among healthy children undergoing general
      anaesthesia for dental rehabilitation. A secondary aim was to assess parental
      distress and attitude to accompanying their children during this procedure. STUDY
      DESIGN: Observational cross sectional study. METHODS: Anxiety levels of 118
      children admitted to the Day Case unit of King Abdullah teaching hospital in
      Irbid, Jordan, for dental rehabilitation under general anaesthesia (GA) were
      assessed at different phases (before and during induction of GA) using the Global
      Mood Score (GMS) with parental presence. The effect of certain variables such as
      age, sex, reason for referral, past GA experience, accompanying parent, and
      parental distress, on children's anxiety during this procedure were assessed
      using multivariate analysis. The level of significance was <0.05. Parental
      distress and attitudes to accompanying their children were assessed using a
      structured questionnaire. RESULTS: There was a significant increase of child
      anxiety on GMS reaching its highest level in phase three (induction phase). A
      multivariate test (MANOVA) showed that previous experience of the child with GA,
      and reason for referral to dental rehabilitation under GA, significantly
      predicted child anxiety (P-value of 0.019 and 0.012) respectively. However,
      parental distress, accompanying person, age, and sex of the child, did not affect
      child anxiety. Parental distress was at its highest level in phase three, mothers
      were significantly more stressed than fathers and parental distress was
      significantly increased when a child was <5 years of age. CONCLUSION: Factors
      contributing to increased child anxiety during induction of GA for dental
      rehabilitation were age, previous GA experience, and referral for GA at a very
      young age. Most parents, especially mothers, were distressed during the induction
      phase, therefore sufficient preoperative preparation of those children and
      parents is necessary to achieve best patient management.

PMID- 20129032
TI  - Short communication. Frequency of dispensing paediatric medicines with high sugar
      content by pharmacists in Barcelona.
AB  - AIM: To determine which high sugar cough syrups sell most frequently in
      pharmacies in Barcelona. METHODS: 300 pharmacies in 10 districts of Barcelona
      (Spain) were visited and data collected on the type of syrup-based medicines
      dispensed most often over a 3-month period in 2008. RESULTS: Data was collected
      in 142 out of 300 pharmacies. The percentage of the medicines sold by group of
      antibiotics (sweetener) were: Augmentine (aspartame) 5.72%; Clamoxyl (sucrose)
      3.28%; Ceclor (sucrose) 3.66%. In the anti-inflammatory group: Junifen 2.0%
      (saccharine sodic); 3.59%, Junifen 4.0% (sodic sucrose); 4.35%, Apiretal Codeine
      (sucrose); 0.31%, Dalsy (sucrose) 39.35%; Febrectal (sodic saccharine): 0.89%.
      CONCLUSIONS: It is very important to advise parents, pharmacists, paediatricians,
      and paediatric dentists about low-sweetener paediatric medicine alternatives to
      control the high content sucrose medicines. The aim should be to reduce the
      intake of over the counter medication.

PMID- 20129033
TI  - Case report: non-syndromic multiple supernumerary teeth localized by cone beam
      computed tomography.
AB  - BACKGROUND: Supernumerary teeth are an infrequent developmental alteration that
      can appear in any area of the dental arches and which are often associated with
      several syndromes such as cleidocranial dysplasia or Gardner syndrome. Multiple
      supernumerary teeth in individuals with no other associated diseases or syndromes
      are very uncommon. CASE REPORT: A 14-year-old male patient presented with 13
      unerupted supernumerary teeth distributed in all four quadrants. TREATMENT: After
      taking a cone beam computed tomograph (CBCT), surgical extraction was performed
      under general anaesthesia in two steps in order to minimize the risk of airway
      constriction by haematoma. FOLLOW-UP: Follow-up examination was uneventful.
      Further orthodontic treatment is planned which will secure the orthodontic
      alignment and correct occlusion. CONCLUSION: Cone beam computed tomography is
      crucial for exact localization, for treatment planning, and for the surgical
      approach in cases of multiple supernumerary teeth.

PMID- 20129034
TI  - Perceptual learning.

PMID- 20129035
TI  - Evolutionary novelties.
AB  - How novel traits arise in organisms has long been a major problem in biology.
      Indeed, the sharpest critiques of Darwin's theory of evolution by natural
      selection often centered on explaining how novel body parts arose. In his
      response to The Origin of Species, St. George J. Mivart challenged Darwin to
      explain the origin of evolutionary novelties such as the mammary gland, asking if
      it was "conceivable that the young of any animal was ever saved from destruction
      by accidentally sucking a drop of scarcely nutritious fluid from an accidentally
      hypertrophied cutaneous gland of its mother?" It is only now that modern
      molecular and genomic tools are being brought to bear on this question that we
      are finally in a position to answer Mivart's challenge and explain one of the
      most fundamental questions of biology: how does novelty arise in evolution?

PMID- 20129036
TI  - Convergent sequence evolution between echolocating bats and dolphins.
AB  - Cases of convergent evolution - where different lineages have evolved similar
      traits independently - are common and have proven central to our understanding of
      selection. Yet convincing examples of adaptive convergence at the sequence level
      are exceptionally rare [1]. The motor protein Prestin is expressed in mammalian
      outer hair cells (OHCs) and is thought to confer high frequency sensitivity and
      selectivity in the mammalian auditory system [2]. We previously reported that the
      Prestin gene has undergone sequence convergence among unrelated lineages of
      echolocating bat [3]. Here we report that this gene has also undergone convergent
      amino acid substitutions in echolocating dolphins, which group with echolocating
      bats in a phylogenetic tree of Prestin. Furthermore, we find evidence that these
      changes were driven by natural selection.

PMID- 20129037
TI  - The hearing gene Prestin unites echolocating bats and whales.
AB  - Echolocation is a sensory mechanism for locating, ranging and identifying objects
      which involves the emission of calls into the environment and listening to the
      echoes returning from objects [1]. Only microbats and toothed whales have
      acquired sophisticated echolocation, indispensable for their orientation and
      foraging [1]. Although the bat and whale biosonars originated independently and
      differ substantially in many aspects [2], we here report the surprising finding
      that the bottlenose dolphin, a toothed whale, is clustered with microbats in the
      gene tree constructed using protein sequences encoded by the hearing gene
      Prestin.

PMID- 20129038
TI  - Mutagenesis: mutating a gene while reading it.
AB  - Is it possible to mutate DNA during transcription? A new study shows that UV
      damaged DNA is deaminated during transcription, which is a probable mechanism
      underlying CC tandem mutations found in the p53 gene in skin cancers.

PMID- 20129039
TI  - Speciation: mosquitoes singing in harmony.
AB  - Anopheles gambiae, a major vector of malaria, is a complex of cryptic species and
      subspecies. A new study describes a remarkable behaviour that might contribute to
      sexual isolation in this species complex: males and females are much more likely
      to show harmonic convergence of wing beat sounds when courting individuals of the
      same type.

PMID- 20129040
TI  - Consciousness: reading the neural signature.
AB  - The brain is the seat of consciousness yet we are unaware of much of our own
      neural processing. What differentiates conscious and unconscious processes? A new
      study suggests the answer might lie in the reproducibility of patterns of neural
      activation.

PMID- 20129041
TI  - Molecular evolution: gene convergence in echolocating mammals.
AB  - The motor protein prestin confers sensitive and selective hearing in mammals.
      Remarkably, prestin amino-acid sequences of echolocating dolphins have converged
      to resemble those of distantly related echolocating bats.

PMID- 20129042
TI  - Developmental evolution: how beetles evolved their shields.
AB  - Beetle forewings are modified into hardened structures called elytra. A recent
      study indicates that the evolution of elytra involved co-opting genes for
      exoskeleton formation into the wing development gene network of beetles on at
      least three separate occasions.

PMID- 20129043
TI  - Brain connectivity: finding a cause.
AB  - A new study combining double-coil transcranial magnetic stimulation (TMS) with
      TMS-induced 'virtual lesions' of the brain shows that the anterior intraparietal
      cortex causally influences interactions between ventral premotor and primary
      motor cortex during grasping.

PMID- 20129044
TI  - MicroRNA processing: battle of the bulge.
AB  - Several recent analyses of plant microRNA precursors define the contributions of
      secondary structure to the precise positions at which processing of these
      precursors occurs.

PMID- 20129045
TI  - Decision making: solving the battle of the fishes.
AB  - A key question about animal group decision making is which conditions promote
      shared or unshared decisions. A recent experiment on sticklebacks demonstrates a
      compromise solution: turn-taking.

PMID- 20129046
TI  - Developmental patterns in spiralian embryos.
AB  - At least five animal phyla exhibit spiralian development, which is characterized
      by striking similarities in the geometry of the early cleavage pattern and the
      fate map of the blastula, along with similarities in larval morphology. Recent
      advances in reconstructing the phylogeny of spiralians and their relatives
      suggest that the common ancestor of a large clade of protostome phyla known as
      the Lophotrochozoa had spiralian development. In this minireview, I describe
      characteristics of spiralian development and some recent insights into its
      mechanisms and evolution.

PMID- 20129047
TI  - Vocal attractiveness increases by averaging.
AB  - Vocal attractiveness has a profound influence on listeners-a bias known as the
      "what sounds beautiful is good" vocal attractiveness stereotype [1]-with tangible
      impact on a voice owner's success at mating, job applications, and/or elections.
      The prevailing view holds that attractive voices are those that signal desirable
      attributes in a potential mate [2-4]-e.g., lower pitch in male voices. However,
      this account does not explain our preferences in more general social contexts in
      which voices of both genders are evaluated. Here we show that averaging voices
      via auditory morphing [5] results in more attractive voices, irrespective of the
      speaker's or listener's gender. Moreover, we show that this phenomenon is largely
      explained by two independent by-products of averaging: a smoother voice texture
      (reduced aperiodicities) and a greater similarity in pitch and timbre with the
      average of all voices (reduced "distance to mean"). These results provide the
      first evidence for a phenomenon of vocal attractiveness increases by averaging,
      analogous to a well-established effect of facial averaging [6, 7]. They highlight
      prototype-based coding [8] as a central feature of voice perception, emphasizing
      the similarity in the mechanisms of face and voice perception.

PMID- 20129048
TI  - RNA switches out in the cold.
AB  - In this issue of Molecular Cell, Giuliodori et al. (2010) describe a cold-induced
      genetic switch made of RNA. Could thermo-sensing RNAs be among the most common
      types of RNA genetic switches?

PMID- 20129049
TI  - Nuclear poly(a)-binding proteins and nuclear degradation: take the mRNA and run?
AB  - Recent work from Lemay et al. (2010) in this issue of Molecular Cell reveals a
      role for a nuclear poly(A)-binding protein in promoting degradation of small
      nucleolar RNAs (snoRNAs) by the nuclear exosome.

PMID- 20129050
TI  - Histone acetylation by HBO1 tightens replication licensing.
AB  - In this issue of Molecular Cell, Miotto and Struhl (2010) suggest that
      replication licensing, the loading of Mcm2-7 onto DNA, is promoted by HBO1
      acetylating histone H4 at replication origins, providing a molecular view of how
      chromatin status influences origin usage.

PMID- 20129051
TI  - The CRISPR system: small RNA-guided defense in bacteria and archaea.
AB  - All cellular systems evolve ways to combat predators and genomic parasites. In
      bacteria and archaea, numerous resistance mechanisms have developed against
      phage. Our understanding of this defensive repertoire has recently been expanded
      to include the CRISPR system of clustered, regularly interspaced short
      palindromic repeats. In this remarkable pathway, short sequence tags from
      invading genetic elements are actively incorporated into the host's CRISPR locus
      to be transcribed and processed into a set of small RNAs that guide the
      destruction of foreign genetic material. Here we review the inner workings of
      this adaptable and heritable immune system and draw comparisons to small RNA
      guided defense mechanisms in eukaryotic cells.

PMID- 20129052
TI  - The cspA mRNA is a thermosensor that modulates translation of the cold-shock
      protein CspA.
AB  - Cold induction of cspA, the paradigm Escherichia coli cold-shock gene, is mainly
      subject to posttranscriptional control, partly promoted by cis-acting elements of
      its transcript, whose secondary structure at 37 degrees C and at cold-shock
      temperature has been elucidated here by enzymatic and chemical probing. The
      structures, which were also validated by mutagenesis, demonstrate that cspA mRNA
      undergoes a temperature-dependent structural rearrangement, likely resulting from
      stabilization in the cold of an otherwise thermodynamically unstable folding
      intermediate. At low temperature, the "cold-shock" structure is more efficiently
      translated and somewhat less susceptible to degradation than the 37 degrees C
      structure. Overall, our data shed light on a molecular mechanism at the basis of
      the cold-shock response, indicating that cspA mRNA is able to sense temperature
      downshifts, adopting functionally distinct structures at different temperatures,
      even without the aid of trans-acting factors. Unlike with other previously
      studied RNA thermometers, these structural rearrangements do not result from
      melting of hairpin structures.

PMID- 20129053
TI  - The nuclear poly(A)-binding protein interacts with the exosome to promote
      synthesis of noncoding small nucleolar RNAs.
AB  - Poly(A)-binding proteins (PABPs) are important to eukaryotic gene expression. In
      the nucleus, the PABP PABPN1 is thought to function in polyadenylation of pre
      mRNAs. Deletion of fission yeast pab2, the homolog of mammalian PABPN1, results
      in transcripts with markedly longer poly(A) tails, but the nature of the
      hyperadenylated transcripts and the mechanism that leads to RNA hyperadenylation
      remain unclear. Here we report that Pab2 functions in the synthesis of noncoding
      RNAs, contrary to the notion that PABPs function exclusively on protein-coding
      mRNAs. Accordingly, the absence of Pab2 leads to the accumulation of
      polyadenylated small nucleolar RNAs (snoRNAs). Our findings suggest that Pab2
      promotes poly(A) tail trimming from pre-snoRNAs by recruiting the nuclear
      exosome. This work unveils a function for the nuclear PABP in snoRNA synthesis
      and provides insights into exosome recruitment to polyadenylated RNAs.

PMID- 20129054
TI  - A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and
      SETDB1 participate in a multimeric complex.
AB  - Lysine 9 of histone 3 (H3K9) can be mono-, di-, or trimethylated, inducing
      distinct effects on gene expression and chromatin compaction. H3K9 methylation
      can be mediated by several histone methyltransferases (HKMTs) that possess mono-,
      di-, or trimethylation activities. Here we provide evidence that a subset of each
      of the main H3K9 HKMTs, G9a/KMT1C, GLP/KMT1D, SETDB1/KMT1E, and Suv39h1/KMT1A,
      coexist in the same megacomplex. Moreover, in Suv39h or G9a null cells, the
      remaining HKMTs are destabilized at the protein level, indicating that the
      integrity of these HKMTs is interdependent. The four HKMTs are recruited to major
      satellite repeats, a known Suv39h1 genomic target, but also to multiple G9a
      target genes. Moreover, we report a functional cooperation between the four H3K9
      HKMTs in the regulation of known G9a target genes. Altogether, our data identify
      a H3K9 methylation multimeric complex.

PMID- 20129056
TI  - Mitochondrial RNA polymerase is needed for activation of the origin of light
      strand DNA replication.
AB  - Mitochondrial DNA is replicated by a unique enzymatic machinery, which is
      distinct from the replication apparatus used for copying the nuclear genome. We
      examine here the mechanisms of origin-specific initiation of lagging-strand DNA
      synthesis in human mitochondria. We demonstrate that the mitochondrial RNA
      polymerase (POLRMT) is the primase required for initiation of DNA synthesis from
      the light-strand origin of DNA replication (OriL). Using only purified POLRMT and
      DNA replication factors, we can faithfully reconstitute OriL-dependent initiation
      in vitro. Leading-strand DNA synthesis is initiated from the heavy-strand origin
      of DNA replication and passes OriL. The single-stranded OriL is exposed and
      adopts a stem-loop structure. At this stage, POLRMT initiates primer synthesis
      from a poly-dT stretch in the single-stranded loop region. After about 25 nt,
      POLRMT is replaced by DNA polymerase gamma, and DNA synthesis commences. Our
      findings demonstrate that POLRMT can function as an origin-specific primase in
      mammalian mitochondria.

PMID- 20129055
TI  - HBO1 histone acetylase activity is essential for DNA replication licensing and
      inhibited by Geminin.
AB  - HBO1, an H4-specific histone acetylase, is a coactivator of the DNA replication
      licensing factor Cdt1. HBO1 acetylase activity is required for licensing, because
      a histone acetylase (HAT)-defective mutant of HBO1 bound at origins is unable to
      load the MCM complex. H4 acetylation at origins is cell-cycle regulated, with
      maximal activity at the G1/S transition, and coexpression of HBO1 and Jade-1
      increases histone acetylation and MCM complex loading. Overexpression of the Set8
      histone H4 tail-binding domain specifically inhibits MCM loading, suggesting that
      histones are a physiologically relevant target for licensing. Lastly, Geminin
      inhibits HBO1 acetylase activity in the context of a Cdt1-HBO1 complex, and it
      associates with origins and inhibits H4 acetylation and licensing in vivo. Thus,
      H4 acetylation at origins by HBO1 is critical for replication licensing by Cdt1,
      and negative regulation of licensing by Geminin is likely to involve inhibition
      of HBO1 histone acetylase activity.

PMID- 20129057
TI  - The molecular chaperone Hsp90 regulates accumulation of DNA polymerase eta at
      replication stalling sites in UV-irradiated cells.
AB  - DNA polymerase eta (Pol eta) is a member of the mammalian Y family polymerases
      and performs error-free translesion synthesis across UV-damaged DNA. For this
      function, Pol eta accumulates in nuclear foci at replication stalling sites via
      its interaction with monoubiquitinated PCNA. However, little is known about the
      posttranslational control mechanisms of Pol eta, which regulate its accumulation
      in replication foci. Here, we report that the molecular chaperone Hsp90 promotes
      UV irradiation-induced nuclear focus formation of Pol eta through control of its
      stability and binding to monoubiquitinated PCNA. Our data indicate that Hsp90
      facilitates the folding of Pol eta into an active form in which PCNA- and
      ubiquitin-binding regions are functional. Furthermore, Hsp90 inhibition
      potentiates UV-induced cytotoxicity and mutagenesis in a Pol eta-dependent
      manner. Our studies identify Hsp90 as an essential regulator of Pol eta-mediated
      translesion synthesis.

PMID- 20129058
TI  - Primase directs the release of DnaC from DnaB.
AB  - An AAA+ ATPase, DnaC, delivers DnaB helicase at the E. coli chromosomal origin by
      a poorly understood process. This report shows that mutant proteins bearing
      alanine substitutions for two conserved arginines in a motif named box VII are
      defective in DNA replication, but this deficiency does not arise from impaired
      interactions with ATP, DnaB, or single-stranded DNA. Despite their ability to
      deliver DnaB to the chromosomal origin to form the prepriming complex, this
      intermediate is inactive. Quantitative analysis of the prepriming complex
      suggests that the DnaB-DnaC complex contains three DnaC monomers per DnaB hexamer
      and that the interaction of primase with DnaB and primer formation triggers the
      release of DnaC, but not the mutants, from DnaB. The interaction of primase with
      DnaB and the release of DnaC mark discrete events in the transition from
      initiation to the elongation stage of DNA replication.

PMID- 20129059
TI  - Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the
      NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.
AB  - The NEDD8-activating enzyme (NAE) initiates a protein homeostatic pathway
      essential for cancer cell growth and survival. MLN4924 is a selective inhibitor
      of NAE currently in clinical trials for the treatment of cancer. Here, we show
      that MLN4924 is a mechanism-based inhibitor of NAE and creates a covalent NEDD8
      MLN4924 adduct catalyzed by the enzyme. The NEDD8-MLN4924 adduct resembles NEDD8
      adenylate, the first intermediate in the NAE reaction cycle, but cannot be
      further utilized in subsequent intraenzyme reactions. The stability of the NEDD8
      MLN4924 adduct within the NAE active site blocks enzyme activity, thereby
      accounting for the potent inhibition of the NEDD8 pathway by MLN4924.
      Importantly, we have determined that compounds resembling MLN4924 demonstrate the
      ability to form analogous adducts with other ubiquitin-like proteins (UBLs)
      catalyzed by their cognate-activating enzymes. These findings reveal insights
      into the mechanism of E1s and suggest a general strategy for selective inhibition
      of UBL conjugation pathways.

PMID- 20129060
TI  - Pin1At encoding a peptidyl-prolyl cis/trans isomerase regulates flowering time in
      Arabidopsis.
AB  - Floral transition in plants is regulated by an integrated network of flowering
      genetic pathways. We show that an Arabidopsis PIN1-type parvulin 1, Pin1At,
      controls floral transition by accelerating cis/trans isomerization of the
      phosphorylated Ser/Thr-Pro motifs in two MADS-domain transcription factors,
      SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) and AGAMOUS-LIKE 24 (AGL24). Pin1At
      regulates flowering, which is genetically mediated by AGL24 and SOC1. Pin1At
      interacts with the phosphorylated AGL24 and SOC1 in vitro and with AGL24 and SOC1
      in vivo and accelerates the cis/trans conformational change of phosphorylated
      Ser/Thr-Pro motifs of AGL24 and SOC1. We further demonstrate that these Ser/Thr
      Pro motifs are important for Pin1At function in promoting flowering through AGL24
      and SOC1 and that the interaction between Pin1At and AGL24 mediates the AGL24
      stability in the nucleus. Taken together, we propose that phosphorylation
      dependent prolyl cis/trans isomerization of key transcription factors is an
      important flowering regulatory mechanism.

PMID- 20129061
TI  - TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad proteins from
      active participation in TGF-beta signaling.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine of key
      importance for controlling embryogenesis and tissue homeostasis. How TGF-beta
      signals are attenuated and terminated is not well understood. Here, we show that
      TMEPAI, a direct target gene of TGF-beta signaling, antagonizes TGF-beta
      signaling by interfering with TGF-beta type I receptor (TbetaRI)-induced R-Smad
      phosphorylation. TMEPAI can directly interact with R-Smads via a Smad interaction
      motif. TMEPAI competes with Smad anchor for receptor activation for R-Smad
      binding, thereby sequestering R-Smads from TbetaRI kinase activation. In
      mammalian cells, ectopic expression of TMEPAI inhibited TGF-beta-dependent
      regulation of plasminogen activator inhibitor-1, JunB, cyclin-dependent kinase
      inhibitors, and c-myc expression, whereas specific knockdown of TMEPAI expression
      prolonged duration of TGF-beta-induced Smad2 and Smad3 phosphorylation and
      concomitantly potentiated cellular responsiveness to TGF-beta. Consistently,
      TMEPAI inhibits activin-mediated mesoderm formation in Xenopus embryos.
      Therefore, TMEPAI participates in a negative feedback loop to control the
      duration and intensity of TGF-beta/Smad signaling.

PMID- 20129062
TI  - A mammalian herpesvirus uses noncanonical expression and processing mechanisms to
      generate viral MicroRNAs.
AB  - Canonical primary microRNA (pri-miRNA) precursors are transcribed by RNA
      polymerase II and then processed by the Drosha endonuclease to generate
      approximately 60 nt pre-miRNA hairpins. Pre-miRNAs in turn are cleaved by Dicer
      to generate mature miRNAs. Previously, some short introns, called miRtrons, were
      reported to fold into pre-miRNA hairpins after splicing and debranching, and
      miRNAs can also be excised by Dicer cleavage of rare endogenous short hairpin
      RNAs. Here we report that the miRNAs encoded by murine gamma-herpesvirus 68
      (MHV68) are also generated via atypical mechanisms. Specifically, MHV68 miRNAs
      are transcribed from RNA polymerase III promoters located within adjacent viral
      tRNA-like sequences. The resultant pri-miRNAs, which bear a 5' tRNA moiety, are
      not processed by Drosha but instead by cellular tRNase Z, which cleaves 3' to the
      tRNA to liberate pre-miRNA hairpins that are then processed by Dicer to yield the
      mature viral miRNAs.

PMID- 20129063
TI  - CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA
      synthesis.
AB  - Monoubiquitination of proliferating cell nuclear antigen (PCNA) is a critical
      posttranslational modification essential for DNA repair by translesion DNA
      synthesis (TLS). The Rad18 E3 ubiquitin ligase cooperates with the E2 Rad6 to
      monoubiquitinate PCNA in response to DNA damage. How PCNA is monoubiquitinated in
      unperturbed cells and whether this plays a role in the repair of DNA associated
      with replication is not known. We show that the CRL4(Cdt2) E3 ubiquitin ligase
      complex promotes PCNA monoubiqutination in proliferating cells in the absence of
      external DNA damage independent of Rad18. PCNA monoubiquitination via CRL4(Cdt2)
      is constitutively antagonized by the action of the ubiquitin-specific protease 1
      (USP1). In vitro, CRL4(Cdt2) monoubiquitinates PCNA at Lys164, the same residue
      that is monoubiquitinated by Rad18. Significantly, CRL4(Cdt2) is required for TLS
      in nondamaged cells via a mechanism that is dependent on PCNA monoubiquitination.
      We propose that CRL4(Cdt2) regulates PCNA-dependent TLS associated with stresses
      accompanying DNA replication.

PMID- 20129064
TI  - Two new genera and species of cystidicolids (Nematoda, Cystidicolidae) from
      marine fishes off New Caledonia.
AB  - Two new nematode species of the family Cystidicolidae, each representing a new
      genus, were recovered from marine perciform fishes off New Caledonia, South
      Pacific: Ascarophisnema tridentatum n. gen., n. sp. from the stomach of the
      Japanese large-eye bream, Gymnocranius euanus (Gunther) (Lethrinidae) and
      Metabronemoides mirabilis n. gen., n. sp. from the stomach of the painted
      sweetlip, Diagramma pictum (Thunberg) (Haemulidae). Ascarophisnema is
      characterized mainly by its cephalic structures (presence of two tooth-like
      projections on either side of the base of each pseudolabium, dorsal and ventral
      inner extensions of each pseudolabium recurved laterally in apical view, and
      submedian sublabia fused together dorsally and ventrally) and the presence of
      trident-like deirids, and Metabronemoides by its unique cephalic structures
      (presence of one dorsal and one ventral labium and four large dorsolateral and
      ventrolateral labia, and absence of sublabia). Rhabdochona gymnocranius
      (considered a species inquirenda) is provisionally transferred to the former
      genus as Ascarophisnema gymnocranius (Yamaguti, 1935) n. comb. To date, a total
      of seven species of cystidicolids are reported from marine fishes off New
      Caledonia.

PMID- 20129065
TI  - The use of geometric morphometrics in understanding shape variability of
      sclerotized haptoral structures of monogeneans (Platyhelminthes) with insights
      into biogeographic variability.
AB  - The sclerotized attachment organ of monogeneans has been widely used to address
      fundamental questions in ecology and evolution. However, traditional morphometric
      techniques appear to be partially inadequate and non-optimal. Traditional linear
      measurements mainly provide information on the size of sclerites but provide very
      little information, if any, on their shape. The shape of sclerites is indeed
      virtually unexplored and its implication for ecological and evolutionary
      processes remains to be analyzed. This study aims to both introduce and
      illustrate the use of geometric morphometrics in order to study sclerites of
      monogeneans in a biogeographic context. To do this, we investigated morphological
      variation patterns among four populations from the Pacific Ocean and six
      monogenean species through traditional and geometric morphometric techniques.
      Unlike the traditional method, the geometric morphometric method yielded a high
      percentage of individuals correctly classified to the four populations, providing
      strong evidence for phenotypic variability, divergence and local adaptation among
      islands without evolutionary constraint. Moreover, the traditional method also
      resulted in inconsistent interpretations of shape variations. This study
      highlighted the limitations that may arise when using traditional morphometric
      techniques and emphasizes that considerable information about the shape of
      sclerotized haptoral parts is added by using geometric morphometrics. Given the
      prominent taxonomic, ecological and evolutionary role of the haptor for
      characterizing monogeneans, we ultimately discuss the potential broad use of
      geometric morphometrics in a wide variety of ecological and evolutionary
      contexts. This powerful approach might allow a more robust estimation of the
      extent to which traditional evolutionary theories based on size of sclerites are
      congruent with their shape.

PMID- 20129066
TI  - The Vereinigung Deutscher Contactlinsen-Spezialisten (VDCO) meeting in Jena.
      Editorial.

PMID- 20129067
TI  - Validation of high-risk HPV tests for primary cervical screening.
AB  - From a clinical point of view, testing for a broad spectrum of high-risk human
      papillomavirus (hrHPV) is only useful when a positive hrHPV test result is
      informative about the presence of high-grade cervical intraepithelial neoplasia
      or cervical cancer (CIN 2 or worse). Two hrHPV tests, i.e. HC2 and GP5+/6+, have
      shown in large clinical trials that they perform better in the detection of CIN
      2+/CIN 3+ lesions than cytology and thus have been clinically validated.
      Consequently these tests are now considered as alternative screening tools for
      cytology in cervical screening. Candidate hrHPV tests to be used for cervical
      screening should have a similar balance between sensitivity and specificity for
      CIN 2+ lesions as these two clinically validated hrHPV tests in order to prevent
      redundant or excessive follow-up procedures for women with transient hrHPV
      infections or hrHPV-positive women without cervical lesions. The data from these
      large prospective clinical studies can be used to set standards for the clinical
      performance and characteristics of the candidate hrHPV test. To prevent costly
      validation trajects of candidate hrHPV tests and based on the available data from
      large clinical studies we demonstrate how guidelines for hrHPV test requirements
      and guidelines for clinical validation of candidate hrHPV tests have been
      developed, and how these guidelines should be used in cervical screening. It is
      expected that the use of these guidelines will facilitate implementation of hrHPV
      testing in primary cervical screening.

PMID- 20129068
TI  - Determination of the diagnostic accuracy of testing for high-risk (HR) human
      papillomavirus (HPV) types 16, 18 and 45 in precancerous cervical lesions:
      preliminary data.
AB  - AIMS: In Germany, cervical cancer screening is regulated by the German Federal
      Ministry of Health and Social Security and is available for all women from the
      age of 20 on the basis of the Papanicolaou (PAP) smear. The purpose of this study
      was to determine the positive predictive value of HR-HPV testing for precancerous
      lesions of the cervix uteri. Therefore, this study especially focused on the
      diagnostic accuracy of testing for one or more of the HPV types 16, 18 and 45 for
      all HR-HPV positive women, since HR-HPV infections with subtypes 16, 18 and 45
      have demonstrated a higher risk of developing cervical cancer [Bulk S, et al. Br
      J Cancer 2006; 94:171-5]. METHODS: Between 2007 and 2008 a total of 586 women
      were recruited: a group of 477 women with a history of known cervical lesions
      and/or HPV infections (eligibility criterion: HR-HPV DNA positive test result
      with HC2T) and a group of 109 women who were examined as part of their routine
      cervical cancer screening. Baseline HR-HPV status was measured at enrollment with
      the FDA-approved Hybrid Capture(R) 2 HPV DNA Test and the HR-HPV 16/18/45 Probe
      Set Test (HC2T, PST; QIAGEN, Hilden, Germany). Both tests use hybrid capture
      hybridization genotyping technology. Cervical smears were classified according to
      the Second Munich Nomenclature (1989). The results were converted to the nearest
      equivalent in the Bethesda system. In general, study subjects were followed up
      semiannually for a period of 1(1/2) years. The histopathological endpoint of CIN
      2-3 lesion was used as a surrogate endpoint. RESULTS: Preliminary data for 194
      women of the risk group (43.5%) and for the complete control group were
      available. To date, CIN 2-3 was confirmed in 77 HR-HPV DNA positive women. 85.7%
      of these lesions were positive for one or more of the HR-HPV types 16, 18 and 45
      (PST+). 88.2% (60/68) of the histologically confirmed CIN 3 lesions and six out
      of nine (66.6%) CIN 2 lesions were positive PST+. Furthermore, all women with a
      histologically confirmed squamous cell carcinoma (n = 4) were PST+. Besides,
      three (50%) out of six detected CIN 1 lesions were PST+. Nonetheless, histology
      confirmed no malignancy in three cases. Two of them were PST+. CONCLUSION: These
      preliminary results demonstrate that starting cervical cancer screening at the
      age of 20 years remains important as seventeen (25%) of the 68 histologically
      verified CIN 3 lesions arose in women who were younger than 30 years.
      Furthermore, our data suggest that adding an HR-HPV test that detects one or more
      of the HR-HPV types 16, 18 and 45 in conjunction with cytology could help to
      identify women with an underlying cervical lesion who have an elevated risk of
      developing severe cervical lesions. This might offer the opportunity of a
      decrease in incidence and mortality rates that are related with invasive cervical
      cancer.

PMID- 20129069
TI  - High genotyping concordance between the digene HPV Genotyping RH Test and the
      Reverse Line Blot genotyping assay on GP5+/6+-PCR products.
AB  - BACKGROUND: Based on epidemiologic studies, 18 mucosal human papillomavirus (HPV)
      types have been classified as (probably) high-risk (HR) (i.e., HPV 16, 18, 26,
      31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, and 82). Recognition of
      HR HPV at the individual type level may be valuable in clinical management of HR
      HPV-positive women. OBJECTIVES: The goal of this study was to evaluate the
      performance of the novel digene HPV Genotyping RH Test (digene RH Test), which
      uses type-specific probes for the 18 HR HPV genotypes, in comparison to the
      established in-house Reverse Line Blot (RLB) genotyping assay on PCR products
      generated with the clinically validated GP5+/6+-PCR method. STUDY DESIGN: GP5+/6+
      amplimers, generated from 493 digene High Risk HPV HC2 DNA Test (HC2)-positive
      and 95 HC2-negative cervical smears, were genotyped by both the digene RH Test
      and the RLB assay. RESULTS: Both genotyping assays demonstrated high concordance
      for overall HR HPV detection (u = 0.886) and type-specific identification of the
      18 HR types (overall u = 0.951, individual u range 0.777 to 1.000) in 493 HC2
      positive samples. The digene RH Test revealed positivity for one or more HR HPV
      type(s) in 86.6% of the HC2-positive women, and negativity was confirmed in 97.9%
      of the HC2-negative women. CONCLUSIONS: The digene HPV Genotyping RH Test
      revealed a high genotyping agreement with the established RLB assay on GP5+/6+
      amplimers. Accordingly, this assay following GP5+/6+-PCR could serve as a follow
      up test in a clinical setting for women who are HC2-positive to identify the
      respective HR HPV genotype(s).

PMID- 20129071
TI  - A German Chlamydia trachomatis screening program employing semi-automated real
      time PCR: results and perspectives.
AB  - BACKGROUND: Genital Chlamydia trachomatis infection is a worldwide public health
      burden. A screening program for C. trachomatis was therefore initiated by the
      public health insurers in Germany ("Gemeinsamer Bundesausschuss", GBA) in April
      2008. OBJECTIVES: To estimate C. trachomatis prevalence from screening 115,766
      asymptomatic females and 20,033 female patients with unspecific abdominal pain.
      STUDY DESIGN: Urine samples (pooled by five for the asymptomatic screening
      subjects) and cervical swabs were analyzed using semi-automated real-time PCR.
      Infection prevalence was determined separately in four categories of women,
      defined by health status (asymptomatic screening vs. non-screening with
      unspecified symptoms) and test material used. Comparative analyses were
      stratified by age and pregnancy status. RESULTS: Experimental evaluation of the
      assay used revealed a detection limit of 379 genome copies/ml urine. For pooled
      urine samples, the positive predictive value was 100% whereas the negative
      predictive value equaled 98.1%. The observed infection prevalence was higher for
      cervical swabs than for urine samples. Prevalence estimates also differed
      significantly between pregnant and non-pregnant adolescents (< or = 20 years),
      irrespective of the test material used (10.2% vs. 7.3% for cervical swabs, 10.9%
      vs. 6.1% for pooled urine samples). CONCLUSIONS: Our retrospective study, based
      upon a very large number of females from all parts of Germany, revealed a high
      infection prevalence in adolescents, particularly in pregnant adolescents,
      thereby justifying the screening directive of the German GBA.

PMID- 20129070
TI  - High-throughput genotyping of high-risk HPV by the digene HPV Genotyping LQ Test
      using GP5+/6+-PCR and xMAP technology.
AB  - BACKGROUND: Epidemiologic studies have classified 18 genotypes of the human
      papillomavirus (HPV) as (probably) high-risk (HR) based on their association with
      cervical cancer, i.e., HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58,
      59, 66, 68, 73, and 82. Given the fact that certain HR HPV types confer an
      increased risk of cervical (pre)cancer, type-specific identification might aid
      clinical management of women tested positive for HR HPV. Therefore, the
      development of robust, high-throughput genotyping assays is important.
      OBJECTIVES: An analytical comparison of the digene HPV Genotyping LQ Test (digene
      LQ Test), capable of identifying 18 HR types using bead-based xMAP suspension
      array technology, with the established Reverse Line Blot (RLB) genotyping assay
      was carried out on amplimers generated with the clinically validated GP5+/6+-PCR
      method. STUDY DESIGN: GP5+/6+ amplimers, generated from 434 digene High Risk HPV
      HC2 DNA Test (HC2)-positive and 95 HC2-negative cervical smears, were genotyped
      by both the digene LQ Test and the RLB genotyping assay. RESULTS: The genotyping
      assays revealed high agreement for overall HR HPV detection (u = 0.884) and type
      specific identification of the 18 HR HPV types (overall u = 0.958, individual u
      range 0.795 to 1.000). The digene LQ Test demonstrated a very good inter
      laboratory reproducibility (u = 0.987). Among the HC2-positive women, the digene
      LQ Test revealed positivity for one or more HR HPV type(s) in 85.9%, and
      negativity was observed in 97.9% of the HC2-negative women. CONCLUSIONS: The
      digene LQ Test demonstrated a high genotyping agreement with the established RLB
      genotyping assay on GP5+/6+ amplimers. This novel assay allows for high
      throughput genotyping following HR HPV testing by HC2.

PMID- 20129072
TI  - Risk-adapted primary HPV cervical cancer screening project in Wolfsburg, Germany-
      experience over 3 years.
AB  - BACKGROUND: Currently, the German cervical cancer screening program encompasses
      an annual cytological Papanicolaou (Pap) smear. However, primary screening for
      cervical cancer using human papillomavirus (HPV) DNA testing detects cervical pre
      cancerous lesions with a significantly higher sensitivity than the Pap smear
      based cytology. OBJECTIVES: In order to develop viable modalities for primary
      cervical screening incorporating DNA testing for high-risk (HR) types of HPV, we
      started a pilot project in the city of Wolfsburg, Germany, in February 2006. This
      program provided a risk-adapted HPV testing-based strategy with defined patient
      pathways and extended screening intervals for women of 30 years or older. We
      report here the data of a 3-year follow-up. STUDY DESIGN: In the context of the
      usual routine screening at their office-based gynecologists, women were offered
      conventional cytology plus the Hybrid Capture 2 (HC2) HPV DNA test. Women with
      inconspicuous cytological findings (Pap I/II) and negative HC2 test were re
      tested after 5 years but continued their annual gynecological examinations. When
      cytology and HC2 were positive, women were immediately referred to colposcopy. In
      women with a negative cytology but positive HC2 test, Pap smear was repeated
      after 6 mo and HC2 testing after 12 mo, and women were called for colposcopy if
      the HC2 test was persistently positive. RESULTS: From February 2006 to December
      2008, 16,724 women agreed to participate in the project. Overall, 906 (5.41%) had
      positive HC2 results and 338 (2.02%) showed atypical Pap smears at recruitment.
      There were 417 (2.48%) women referred for colposcopy, 104 of whom were diagnosed
      with cervical intraepithelial neoplasia (CIN) 3 or worse, including 8 invasive
      cancers and 8 adenocarcinoma in situ (ACIS). No case of CIN 3 or worse occurred
      in HC2 negative women. CONCLUSIONS: The presented risk-adapted Wolfsburg Cervical
      Cancer Prevention Project ("Wolfsburg Model") has been shown to be effective and
      feasible in identifying women at risk and for avoiding unnecessary procedures for
      those who are double negative, thus allowing longer screening intervals and cost
      savings. Acceptance rates for the program were high for both participating women
      and gynecologists.

PMID- 20129073
TI  - The combined use of viral transcriptional and post-transcriptional regulatory
      elements to improve baculovirus-mediated transient gene expression in human
      embryonic stem cells.
AB  - Transient gene expression is one possible approach to manipulate the signaling
      pathways that control the proliferation and differentiation of human embryonic
      stem (hES) cells. We tested in hES cells a range of baculoviral vectors with a
      human elongation factor-1alpha promoter and various viral regulatory elements and
      observed the most dramatic augmenting effect on the transient expression when the
      promoter was used together with the human cytomegalovirus immediate-early gene
      enhancer and the woodchuck hepatitis virus post-transcriptional regulatory
      elements. This vector provided a 1.6-fold increase in the percentage of
      transduced cells (up to 72%) over a vector containing the elongation factor
      1alpha promoter alone. The effective baculoviral transduction of hES cells did
      not affect cell proliferation, expression of embryonic stem cell markers and
      teratoma formation. This new viral vector for temporary transgene expression
      might become a useful tool for developmental biology studies and biomedical
      applications of hES cells.

PMID- 20129074
TI  - An efficient treatment for detoxification process of cassava starch by plant cell
      wall-degrading enzymes.
AB  - The objective of this work was to remove linamarin in starch from cassava
      (Manihot esculenta Crantz cv. KU-50) roots, a high-cyanogen variety by using
      plant cell wall-degrading enzymes, xylanase and cellulase. The combination of
      xylanase from Bacillus firmus K-1 and xylanase and cellulase from Paenibacillus
      curdlanolyticus B-6 at the ratio of 1:9 showed the maximum synergism at 1.8 times
      for hydrolyzing cassava cortex cell walls and releasing linamarase. Combined
      enzyme treatment enhanced linamarin liberation from the parenchyma by 90%. In
      addition, when the combined enzymes were applied for detoxification during
      cassava starch production, a low-cyanide-product was obtained with decreased
      linamarin concentration (96%) compared to non-enzyme treated tissues. Based on
      these results, xylanase and cellulase treatment is a good method for low-cyanide
      cassava starch production and could be applied for detoxification of cassava
      products during processing.

PMID- 20129075
TI  - Development of a homogeneous competitive immunoassay for phosphorylated protein
      antigen based on the enhanced fluorescence resonance energy transfer technology.
AB  - We describe a homogeneous competitive immunoassay for a phosphorylated protein
      antigen. The assay takes advantage of the enhanced fluorescence resonance energy
      transfer (FRET) technology, which has a unique characteristic that the FRET
      signal is increased by the specific interaction of two fluorolabeled leucine
      zippers. We chose extracellular signal-regulated kinase (ERK) as a model antigen
      and constructed two molecular probes in which either anti-phosphorylation site
      antibody or the antigen peptide was chemically conjugated to the enhanced FRET
      probes. While these molecular probes indicated sufficient FRET signal without
      antigen, they displayed a significant change in the fluorescent spectrum by
      mixing with phosphorylated antigens. With this competitive enhanced FRET
      immunoassay, a phosphorylated ERK concentration within the range from 15 nM to
      250 nM could be determined. Because the assay is very simple, it would be applied
      to not only in vitro assay but also in vivo detection of protein phosphorylation.

PMID- 20129076
TI  - Helvellisin, a novel alkaline protease from the wild ascomycete mushroom Helvella
      lacunosa.
AB  - A 33.5-kDa serine protease designated as helvellisin was isolated from dried
      fruiting bodies of the wild ascomycete mushroom Helvella lacunosa. It was
      purified by using a procedure which entailed ion exchange chromatography on DEAE
      cellulose, CM-Sepharose, Q-Sepharose, and FPLC-gel filtration on Superdex 75. The
      protease was characterized by unique N-terminal amino acid sequence,
      thermostability and pH stability. The protease exhibited a pH optimum of 11.0 and
      a temperature optimum of 65 degrees C, with about 40% activity remaining at 87
      degrees C and pH 5 and 13. Helvellisin demonstrated a protease activity of 14600
      U/mg toward casein. The K(m) of the purified protease for casein was 3.81 mg/ml
      at pH 11.0 and 37 degrees C. The V(max) was 5.35x10(-2) mg ml(-1) min(-1). It was
      adversely affected by phenylmethylsulfonyl fluoride, suggesting that it is serine
      protease. The activity of the protease was enhanced by Mg(2+), Fe(2+) and Mn(2+),
      but was curtailed by Cu(2+), Hg(2+) and Fe(3+). It was devoid of antifungal and
      ribonuclease activities.

PMID- 20129077
TI  - Cloning and characterization of grpE in Acetobacter pasteurianus NBRC 3283.
AB  - The grpE gene in Acetobacter pasteurianus NBRC 3283 was cloned and characterized,
      to elucidate the mechanism underlying the resistance of acetic acid bacteria to
      the stressors existing during acetic acid fermentation. This gene was found to be
      located in tandem with two related genes, appearing on the genome in the order
      grpE-dnaK-dnaJ. A sigma(32)-type promoter sequence was found in the upstream
      region of grpE. The relative transcription levels of grpE, dnaK, and dnaJ mRNA
      were in the ratio of approximately 1:2:0.1, and the genes were transcribed as
      grpE-dnaK, dnaK, and dnaJ. The transcription level of grpE was elevated by heat
      shock and treatment with ethanol. Co-overexpression of GrpE with DnaK/J in cells
      resulted in improved growth compared to the single overexpression of DnaK/J in
      high temperature or ethanol-containing conditions, suggesting that GrpE acts
      cooperatively with DnaK/J for expressing resistance to those stressors considered
      to exist during acetic acid fermentation. Our findings indicate that GrpE is
      closely associated with adaptation to stressors in A. pasteurianus and may play
      an important role in acetic acid fermentation.

PMID- 20129078
TI  - Elevation of ceramide in Acetobacter malorum S24 by low pH stress and high
      temperature stress.
AB  - Acetic acid bacteria have unique and highly pure membrane lipid components, such
      as 2-hydroxypalmitoyl-sphinganine (dihydroceramide) and can grow and produce
      acetic acid at around pH 3.0, suggesting that ceramide in cell membranes may be
      involved in the tolerance to acidic pH. Acetobacter malorum S24 was selected for
      the production of ceramide and grown in YPG medium containing 0.8% ethanol.
      Ceramide biosynthesis was induced at pH 4 and below, suggesting that ceramide
      biosynthesis is induced by low pH stress. Elevation of ceramide was also induced
      by high temperature stress (40-70 degrees C). After the strain was cultured in an
      optimal growth medium, the cells were collected and treated at pH 3 and 40
      degrees C for 4 days, resulting in a 30-fold elevation of both the yield and
      content of ceramide.

PMID- 20129079
TI  - Effect of oxygen concentration in gas phase on sporulation and individual
      ganoderic acids accumulation in liquid static culture of Ganoderma lucidum.
AB  - Effects of oxygen concentration within 21-100% in gaseous phase on the morphology
      and ganoderic acids (GAs) production by Ganoderma lucidum in liquid static
      culture were studied. A higher oxygen concentration increased individual GAs
      production, and more spores and higher total GA content were obtained at an
      oxygen level of 80%.

PMID- 20129080
TI  - Continuous ethanol fermentation from non-sulfuric acid-washed molasses using
      traditional stirred tank reactors and the flocculating yeast strain KF-7.
AB  - Waste molasses is one of the most important feedstock for ethanol production in
      Brazil as well as in many Southeast Asian countries, including China. Sulfuric
      acid pretreatment is employed in most ethanol distilleries in China to control
      bacterial contamination, which results in difficulties in the treatment of
      wastewater containing high levels of sulfate ions. In this study, a high
      efficiency, non-sterilized, continuous ethanol fermentation process without
      sulfuric acid pretreatment was developed using the flocculating yeast strain KF-7
      and the widely utilized, traditional, stirred tank reactors. An alternative
      molasses medium feeding method, which differs from traditional methods, is
      proposed that effectively controls bacterial contamination. Separate feeding of
      1.2-fold diluted molasses and tap water into the reactor proved to be effective
      against bacterial contamination during long-term continuous fermentation. By
      feeding yeast cells with high metabolic activity to the second reactor, a two
      stage continuous fermentation process that yielded a high ethanol concentration
      of 80 g/l as well as high ethanol productivity of 6.6 g/l/h was successfully
      operated for more than one month. This fermentation process can be applied to
      ethanol distilleries in which traditional tank reactors are used.

PMID- 20129081
TI  - Enhanced heavy metal phytoextraction by Echinochloa crus-galli using root
      exudates.
AB  - Heavy metal uptake and growth by Echinochloa crus-galli were investigated to
      determine if the use of root exudates enhanced phytoextraction. E. crus-galli
      were planted in soils contaminated with 600 mg kg(-1) Pb, 40 mg kg(-1) Cd and 100
      mg kg(-1) Cu. E. crus-galli were then cultivated with and without root exudates
      from Belamcanda chinensis for 4 weeks. The growth of E. crus-galli in metal
      contaminated soils that contained root exudates showed increased roots and shoots
      when compared to E. crus-galli grown without root exudates (p<0.05). In addition,
      the accumulation of metal in E. crus-galli that was cultivated with the root
      exudates was two- to fourfold higher than in plants that were cultivated without
      the root exudates. The exchangeable soil fraction in the rhizosphere of E. crus
      galli grown with root exudates was greater than when E. crus-galli was grown
      without root exudates. Finally, the BCF and TF values of Cd, Cu and Pb were
      greater when the root exudates were added (p<0.05). Taken together, these results
      indicate that root exudates can be used as a natural chelating agent to enhance
      phytoextraction.

PMID- 20129082
TI  - Effect of monosaccharides composing glycosaminoglycans on type 2 collagen
      accumulation in a three-dimensional culture of chondrocytes.
AB  - The effect of the addition of monosaccharides composing glycosaminoglycans (GAGs)
      on the accumulation of type 2 collagen (COL(II)) in a three-dimensional (3D)
      culture of porcine chondrocyte cells was investigated for possible application to
      cartilage regenerative medicine. Primary chondrocytes from porcine cartilage were
      cultivated in three-dimension employing atelo collagen gel for 3 weeks with the
      addition of several saccharides. The addition of d-glucuronic acid (d-GlcA), N
      acetyl-d-galactosamine (d-GalNAc), chondroitin sulfate C (CSC), d-galactose, N
      acetyl-d-glucosamine, and l-iduronic acid increased markedly not aggrecan but
      COL(II) accumulation although the addition of d-fructose and d-mannose not
      composing GAGs did not show such an effect. The addition of d-GlcA and d-GalNAc
      had no synergistic effect. The addition of CSC, d-GlcA, and d-GalNAc also
      increased COL(II) mRNA expression while aggrecan mRNA expression was not
      increased by these compounds. In conclusion, the addition of monosaccharides
      composing GAGs might be valuable for increasing COL(II) accumulation in the 3D
      culture of chondrocytes.

PMID- 20129083
TI  - Myogenic induction of human mesenchymal stem cells by culture on dendrimer
      immobilized surface with d-glucose display.
AB  - Culture surfaces were designed by immobilizing dendrimer with d-glucose display,
      that is, 1st-generation (G1) and 3rd-generation (G3) dendrimer surfaces. In the
      cultures of human mesenchymal stem cells (hMSCs), the effect of the prepared
      culture surfaces was examined in terms of regulating cell morphology and
      differentiation. The time-lapse observation revealed that the cells on the G3
      surface showed more dynamic behaviors of temporal stretching and contracting
      associated with stimulated migration, as compared with the cells on the G1 and
      plain surfaces. On the G3 surface, moreover, a frequency of round-shaped cells
      increased, and spreading of the cells was appreciably suppressed. From the
      cytoskeletal staining of F-actin, it was found that the immature stress fibers
      were of significance in the cells on the G3 surface. In addition, the cells on
      the G3 surface expressed RhoA inactivation and Rac1 activation during the
      culture, indicating that the G3 surface permits the regulation of RhoA and Rac1
      expression associated with altering in cellular morphology and migratory
      behaviors. It was also found that desmin expression was, in particular, promoted
      on the G3 surface, thus supporting the consideration that a balance of Rho family
      GTPases activation induces myogenesis in hMSCs. The current results suggest that
      the dendrimer surface can be a potential tool for the guided differentiation of
      hMSCs directing to myocyte-like cells in the absence of an aqueous myogenesis
      inducing factor.

PMID- 20129084
TI  - Onset timing of transient gene expression depends on cell division.
AB  - By using the time lapse of both phase-contrast and fluorescent images, we
      examined the morphology of cells and the dynamics of gene expression (EGFP). We
      applied k-means clustering to the time course data of fluorescent intensity of
      EGFP and successfully found four subpopulations. Discriminating the appropriate
      clusters and investigating the details of them, we found that almost all cells
      express the transfected gene after cell division and also found there is a strong
      correlation between onset timing and cell division. This result suggested that it
      is possible to normalize the dynamics of gene by arranging the onset timing of
      gene expression or by arranging the cell division.

PMID- 20129085
TI  - Proliferative effects on neural stem/progenitor cells of a sulfated
      polysaccharide purified from the sea cucumber Stichopus japonicus.
AB  - To test the effects of a sulfated polysaccharide, Haishen (HS) on the viability
      and proliferation of neural stem/progenitor cells (NSPCs), we isolated the
      polysaccharide from the body wall of the sea cucumber Stichopus japonicus by
      enzymolysis extraction, anion-exchange and gel-permeation chromatography. HS is a
      highly sulfated fucoidan with a molecular weight of 4.23x10(5) Da. Due to its
      safety being of invertebrate origin they are less likely to contain infectious
      agents, the effects of HS on the viability and proliferation of NSPCs in vitro
      were examined by MTT assay, BrdU labeling and neurosphere formation assay,
      respectively. Our results showed that HS alone increased NSPC viability in a dose
      dependent manner. Moreover, HS acted synergistically with fibroblast growth
      factor-2 (FGF-2) but not epidermal growth factor (EGF) to enhance the
      proliferation of NSPCs. Finally, HS did not induce apoptosis of NSPCs. Our
      findings suggest that HS can serve as an adjuvant for promoting the proliferation
      of NSPCs.

PMID- 20129086
TI  - A mass separation of chondrocytes from cartilage tissue utilizing an automatic
      crushing device.
AB  - Porcine articular cartilage tissue was crushed using Multi-Beads-Shocker() and
      digested with trypsin and collagenase type II. Chondrocyte cell yield was
      maximized by automatic crushing for 10 s, which was 4 times that by manual dicing
      with a surgical blade and might be useful for the automation of the cell
      processing.

PMID- 20129087
TI  - In vitro generation of anti-hepatitis B monoclonal antibodies from a single
      plasma cell using single-cell RT-PCR and cell-free protein synthesis.
AB  - Monoclonal antibodies (mAbs) are an effective tool in therapeutics and
      diagnostics. A novel approach called the single-cell RT-PCR-linked in vitro
      expression system (SICREX) enables the high-throughput generation and screening
      of mAbs from single B cells. In this paper, instead of using B cells, cDNAs were
      synthesized from single plasma cells of an immunized mouse spleen. The light
      chain (Lc) and the Fd portion of the heavy chain (Hc) genes of each cell were
      amplified separately and followed by overlapping PCR to add a T7 promoter, a
      ribosome-binding site, and a T7 terminator. The paired Lc and Hc genes were
      simultaneously expressed by an Escherichia coli in vitro transcription and
      translation system followed by ELISA to measure their affinity for the antigen. A
      Fab fragment with affinity against the antigen was obtained from plasma cells of
      an immunized mouse with hepatitis B surface antigen (HBsAg).

PMID- 20129088
TI  - Optimization of a real-time PCR assay to quantitate airborne fungi collected on a
      gelatin filter.
AB  - The present study aimed to optimize a real-time PCR assay to quantitate airborne
      fungi collected on a gelatin filter. In particular, the study optimized
      conditions for the DNA extraction and real-time PCR amplification to accurately
      measure airborne fungal concentrations. First, time of fine bead homogenization
      to extract the DNA from fungal cells was optimized to maximize the DNA yield and
      prepare the DNA suitable for sensitive and precise quantification by a subsequent
      real-time PCR analysis. Second, a condition for the real-time PCR amplification
      was optimized to successfully amplify and quantitate the extracted fungal DNA. In
      particular, a dilution ratio of the DNA extracts to be introduced to PCR was
      optimized to achieve an appropriate balance between mitigating PCR inhibition and
      securing detection sensitivity. Since concentrations of airborne fungi generally
      observed in indoor and outdoor environments (i.e., 10(1)-10(4) CFU m(-3)) were
      found to be near the limit of quantification by the generally-used molecular
      based detection technique in conjunction with use of gelatin filters,
      optimizations of these conditions were found to be crucial. Our preliminary
      result showed that a culture-based method underestimated concentrations of
      airborne environmental fungi by 1 to 2 orders of magnitude compared to those
      characterized by the real-time PCR assay.

PMID- 20129089
TI  - Pyrolysis GC-MS-based metabolite fingerprinting for quality evaluation of
      commercial Angelica acutiloba roots.
AB  - Metabolite fingerprinting was applied in the attempt to evaluate the quality of
      Angelica acutiloba dried roots (Yamato-toki). A pyrolyser coupled to a gas
      chromatography mass spectrometer (PY-GC-MS) was used to obtain higher chemical
      universality by analyzing whole compounds including high molecular weight
      metabolites. The machine was relatively fast and easy to use, with no sample
      preparation procedure required. Multivariate pattern recognition methods,
      specifically principal component analysis (PCA) and partial least square
      discriminant analysis (PLS-DA), were successful in discriminating various toki
      samples. In addition, an enhanced understanding of the dominant relationship of
      cultivation area to quality evaluation was conceptualized and therefore applied
      to the construction of a PLS-DA classification model which provided the basis for
      accurate and reliable predictivity.

PMID- 20129090
TI  - Semi-quantitative discrimination of HBV mutants using allele-specific
      oligonucleotide hybridization with Handy Bio-Strand.
AB  - The analysis of hepatitis B virus (HBV) mutations is important for understanding
      HBV progression and for deciding on appropriate clinical treatments. However, it
      is difficult to determine the quantitative abundance of various mutants in
      heterogeneous mixtures by conventional methods such as direct sequencing or the
      TaqMan assay. In this study, we investigated the possibility of using both allele
      specific oligonucleotide hybridization (ASOH) and allele-specific oligonucleotide
      competitive hybridization (ASOCH) with the Handy Bio-Strand system for the
      quantitative identification of three well-defined HBV variants: the basal core
      promoter (BCP) mutations (nt1762 and nt1764), the pre-core (PC) mutation
      (nt1896), and variance at nt1858. Using standardized mixtures of wild-type and
      mutant DNA, optimal hybridization conditions for ASOH and ASOCH were determined.
      Next, the performance of these methods was evaluated using actual serum DNAs from
      HBV patients. Excellent reproducibility was obtained both in the analysis of
      internal positive controls and in the semi-quantitative categorization of
      heterogeneous viral mixtures into five abundance groups (0%, 25%, 50%, 75%, and
      100% mutant virus). Combined with real-time PCR to determine the HBV viral load,
      this hybridization method offers a new tool with applications both in HBV
      clinical research and treatment.

PMID- 20129091
TI  - Purification of polygalacturonase from solid-state cultures of Aspergillus
      carbonarius.
AB  - Purification of polygalacturonase (PG) from the cultures of Aspergillus
      carbonarius obtained by acetate buffer extraction after solid-state fermentation
      was attempted by integrated membrane process and alginate affinity precipitation.
      The carbohydrates were completely eliminated (98%-99%) with a PG recovery of 72%
      80% during integrated membrane process, which would otherwise interfere with the
      purification process and lead to enzyme loss. However, specific activity of PG
      did not improve (1.19-1.21 fold) due to the presence of other similar molecular
      mass proteins. Under optimum conditions of affinity precipitation, the specific
      activity of PG enhanced to 2450 U/mg (4 fold) with almost complete elimination of
      carbohydrates and colour compounds resulting in a PG recovery of 61%. PG purity
      obtained with ultrafiltration (UF) was comparable with the conventional dialysis
      during desalting eluted PG, besides UF rendered a concentrated PG. The enzyme
      purity stated was as descend by SDS-PAGE. The results suggested suitability of
      affinity precipitation for PG purification from solid-state cultures and the
      potential of UF as a single step process for handling eluted PG.

PMID- 20129092
TI  - In vitro synthesis of high molecular weight rubber by Hevea small rubber
      particles.
AB  - Hevea brasiliensis is one of few higher plants producing the commercial natural
      rubber used in many significant applications. The biosynthesis of high molecular
      weight rubber molecules by the higher plants has not been clarified yet. Here,
      the in vitro rubber biosynthesis was performed by using enzymatically active
      small rubber particles (SRP) from Hevea. The mechanism of the in vitro rubber
      synthesis was investigated by the molecular weight distribution (MWD). The highly
      purified SRP prepared by gel filtration and centrifugation in the presence of
      Triton((R)) X-100 showed the low isopentenyl diphosphate (IPP) incorporation for
      the chain extension mechanism of pre-existing rubber. The MWD of in vitro rubber
      elongated from the pre-existing rubber chains in SRP was analyzed for the first
      time in the case of H. brasiliensis by incubating without the addition of any
      initiator. The rubber transferase activity of 70% incorporation of the added IPP
      (w/w) was obtained when farnesyl diphosphate was present as the allylic
      diphosphate initiator. The in vitro synthesized rubber showed a typical bimodal
      MWD of high and low molecular weight fractions in GPC analysis, which was similar
      to that of the in vivo rubber with peaks at around 10(6) and 10(5) Da or lower.
      The reaction time independence and dependence of molecular weight of high and low
      molecular weight fractions, respectively, indicated that the high molecular
      weight rubber was synthesized from the chain extension of pre-existing rubber
      molecules whereas the lower one was from the chain elongation of rubber molecules
      newly synthesized from the added allylic substrates.

PMID- 20129093
TI  - Characterization of Aspergillus oryzae glycoside hydrolase family 43 beta
      xylosidase expressed in Escherichia coli.
AB  - This is the first report of glycoside hydrolase family 43 beta-xylosidase from
      Aspergillus oryzae. To characterize this enzyme, the recombinant enzyme was
      expressed in Escherichia coli. Unlike known beta-xylosidases from fungal origins,
      the enzyme did not show substrate ambiguity and was stable at alkaline pH.

PMID- 20129094
TI  - Protection against diesel oil toxicity by sodium chloride-induced
      exopolysaccharides in Acinetobacter sp. strain DR1.
AB  - Acinetobacter sp. strain DR1 is capable of growth on diesel oil. Interestingly,
      the degradation of diesel oil by the strain DR1 is enhanced in the presence of
      sodium chloride (NaCl). However, the growth rate of strain DR1 is not affected by
      the presence of NaCl. Northern blot analysis has also demonstrated that the
      effect of NaCl on the degradation of diesel oil is not attributable to increased
      levels of alkane hydroxylase (AlkM-type) gene expression. Rather, we have noted
      an increase in the exopolysaccharide (EPS) yields of strain DR1 under high NaCl
      conditions (9-fold). The lag-time of diesel oil biodegradation was significantly
      shorter in the strain DR1 with exogenous EPS than in the controls, although EPS
      alone does not support the growth of strain DR1. The recovery of strain DR1 when
      exposed to diesel oil was accelerated when exogenous EPS was added to the medium.
      The overproduction of EPS was also noted in the presence of diesel oil and n
      hexadecane. The data indicated that EPS overproduction might play a protective
      role against diesel oil toxicity. Along with the results of the soil microcosm
      tests, the data presented herein demonstrated that NaCl-induced EPS is associated
      with a reduction in diesel oil toxicity, and thus increases diesel oil
      biodegradation in Acinetobacter sp. strain DR1.

PMID- 20129095
TI  - Partial nitrification treatment for high ammonium wastewater from magnesium
      ammonium phosphate process of methane fermentation digester liquor.
AB  - This study investigated partial nitrification treatment of methane fermentation
      digester liquor effluent from magnesium ammonium phosphate precipitation process
      in a swim-bed reactor. The reactor was operated at a temperature of 35 degrees C
      and pH between 7.5 and 7.8. Partial nitrification was achieved at the onset of
      the experiments even though conventional activated sludge was used as seed
      sludge. The maximum nitrite production rate was 1.0 kg NO(2)-N/m(3)/d at a
      nitrogen loading rate of 2.0 kg-N/m(3)/d. The average effluent NO(2)-N/NH(4)-N
      ratio and the effluent NO(3)-N concentration were 1.04+/-0.34 and 5.7 mg/l,
      respectively, during the stable experiment periods. After 150 days of operation,
      the sludge volume index value decreased to 15 ml/g and the mean particle size of
      suspended sludge increased by approximately 3 times from 80 to 260 mum.
      Comparison of mineral analysis between the seed sludge and the partial
      nitrification sludge demonstrated that the mineral content of the latter
      increased approximately three-fold in comparison to that of the former. High Ca
      concentration was considered to be closely related to dense floc formation and
      superior settleability of the sludge. Both DGGE and DNA clone analysis verified
      that there were significant microbiological differences between the samples taken
      at different time periods. Nitrosomonas was confirmed to be the predominant
      species after stable partial nitrification performance was obtained. The overall
      results of this study validated our previous results that swim-bed reactor
      technology could be successfully used as a pre-treatment technology for anammox
      treatment.

PMID- 20129096
TI  - Characterization of microorganisms at different landfill depths using carbon
      utilization patterns and 16S rRNA gene based T-RFLP.
AB  - A borehole core from 20 m depth of a Japanese landfill was characterized
      chemically and microbially. The borehole core sample was typically divided into 5
      waste layers; 2.4-4.0 m, 5.7-8.5 m, 9.25-9.6 m, 9.77-14.9 m, and 15.9-17.86 m
      depths. The waste layers' ages spanned about 14 years between the bottom and top.
      Archaeal 16S rRNA gene and eubacterial 16S rRNA gene in the waste samples at
      their respective levels were 9.8 x 10(5)-7.2 x 10(7) and 1.2 x 10(7)-7.2 x 10(9)
      copy/g-wet. Similar to populations of viable and culturable bacteria, those
      populations were high at 7.0 m and 17.5 m depth, but low at 3.0 m depth. The
      microorganisms' phenotypes and genotypes were evaluated, respectively, using
      carbon-utilization tests and by eubacterial 16S rRNA gene based T-RFLP. Low
      dominance of the VFA-utilizing bacteria in samples and low concentrations of VFAs
      in all waste layers suggest that the organic decomposition in this landfill site
      remained. Gamma-proteobacteria dominated the microbial community at 17.5 m depth.
      Clostridia were detected at 7.0, 11.5, and 17.5 m depths, suggesting strict
      anaerobic conditions in these deep layers. The Shannon-Weaver diversity index
      showed lower values at 3.0 m and 11.5 m depth with a T-RF pattern. The diversity
      index calculated from the carbon-utilization pattern increased slightly with
      depth at the landfill site. The landfill-site waste layers are expected to be
      mutually isolated and to form unique microbial communities depending on the
      buried wastes' composition, temperature, moisture content, and pressure inside
      the landfill.

PMID- 20129097
TI  - Scale-up fermentation of echinocandin type antibiotic FR901379.
AB  - Industrial-scale production of FR901379 (WF11899A), which is a novel echinocandin
      type of lipopeptide antibiotic produced by mutant strain M-7 from Coleophoma
      empetri F-11899 (FERM BP-2635), was demonstrated. In order to achieve high-level
      production in fermentor culture, the medium previously developed was modified, in
      which three types of organic nitrogen were replaced by ammonium sulfate and corn
      steep liquor. To eliminate increase in viscosity, carbon source was
      intermittently fed. The viscosity was reduced from 20,000 cP to less than 10,000
      cP. The FULLZONE impeller was introduced in the fermentor culture for sufficient
      mixing. Mixing time was quite improved and high reproducibility was achieved.
      Surprisingly, the viscosity of the broth was reduced to 1000 cP in a 4 m(3) scale
      fermentor. When k(L)a was selected as an index for scale-up and industrial scale
      production using a 15 m(3) fermentor with the FULLZONE impeller was conducted,
      FR901379 production was successfully obtained at more than 50 U/mL, almost the
      same level as with the 0.03 m(3) and 4 m(3) fermentors. In addition, superior
      reproducibility was obtained, and 500-fold scale-up was successfully achieved.

PMID- 20129098
TI  - Abeta/Cu-catalyzed oxidation of cholesterol in 1,2-dipalmitoyl
      phosphatidylcholine liposome membrane.
AB  - The amyloid beta protein with 42 amino acid residues (Abeta), which is a
      causative protein of Alzheimer's disease (AD), forms the complex with copper (II)
      to induce the cholesterol oxidase-like activity by the proton transfer from the
      cholesterol. In this study, the oxidation of cholesterol by Abeta/Cu complex was
      investigated on the surface of the zwitterionic phospholipid liposome including
      the bound water advantageous for the enhancement of the proton transfer. The
      bound water was pooled by the formation of cholesterol-rich domain within
      liposomes. The resulting reactivity was enhanced by the proton transfer mediated
      by the bound water.

PMID- 20129099
TI  - Favorable effect of very low initial K(L)a value on xylitol production from
      xylose by a self-isolated strain of Pichia guilliermondii.
AB  - Xylitol production from xylose by a self-isolated furfural and 5-hydroxymethyl
      furfural assimilating Pichia guilliermondii was studied under oxygen limitation.
      An extremely low initial volumetric oxygen transfer coefficient (0.075 h(-1)) was
      found most favorable to the xylitol production with yield of 0.61 g g(-1).
      Related enzymes activities were also investigated and discussed.

PMID- 20129100
TI  - Monitoring growth and movement of Ralstonia solanacearum cells harboring plasmid
      pRSS12 derived from bacteriophage phiRSS1.
AB  - We monitored growth and movement of Ralstonia solanacearum harboring the plasmid
      pRSS12 in tomato seedlings. The plasmid contains a gene for green fluorescent
      protein (GFP) and is stably maintained in R. solanacearum cells without selection
      pressure. Bacteria harboring the plasmid can be tracked in planta by visualizing
      GFP fluorescence. Stems of seedlings were infected with R. solanacearum cells
      transformed with pRSS12, and bacterial growth and movement, particularly around
      the vascular bundles, were monitored for more than 7 days. Our results showed
      that vascular bundles are independent of each other within the stem, and that it
      takes a long time for R. solanacearum cells to migrate from one vascular bundle
      to another. For real-time monitoring of bacteria in planta, tomato seedlings were
      grown on agar medium and bacterial suspension was applied to the root apex. The
      bacterial invasion process was monitored by fluorescent microscopy. Bacteria
      invaded taproots within 6 h, and movement of the bacteria was observed until 144
      h after inoculation. In susceptible tomato cultivars, strong GFP fluorescence was
      observed in hypocotyls and lateral roots as well as the taproot. In resistant
      cultivars, however, GFP fluorescence was rarely observed on lateral roots. Our
      results show that this monitoring system can be used to assess bacterial
      pathogenicity efficiently.

PMID- 20129101
TI  - The impact of the overexpression of human UDP-galactose transporter gene hUGT1 in
      tobacco plants.
AB  - When the human UDP-galactose transporter 1 gene (hUGT1) was introduced into
      tobacco plants, the plants displayed enhanced growth during cultivation, and
      axillary shoots had an altered determinate growth habit, elongating beyond the
      primary shoots and having a sympodial growth pattern similar to that observed in
      tomatoes at a late cultivation stage. The architecture and properties of tissues
      in hUGT1-transgenic plants were also altered. The leaves had an increase in
      thickness, due to an increased amount of spongy tissue, and a higher content of
      chlorophyll a and b; the stems had an increased number of xylem vessels and
      accumulated lignin and arabinogalactan proteins (AGPs). Some of these
      characteristics resembled a gibberellin (GA)-responsive phenotype, suggesting
      involvement of GA. RT-PCR-based analysis of genes involved in GA biosynthesis
      suggested that the GA biosynthetic pathway was not activated. However, an
      increase in the proportion of galactose in polysaccharide side chains of AGPs was
      detected. These results suggested that because of higher UDP-galactose transport
      from the cytosol to the Golgi apparatus, galactose incorporation into
      polysaccharide side chains of AGP is involved in the gibberellin response,
      resulting in morphological and architectural changes.

PMID- 20129102
TI  - Effect of the sequence context of the AUG initiation codon on the rate of
      translation in dicotyledonous and monocotyledonous plant cells.
AB  - The sequence context around the AUG initiation codon strongly contributes to the
      translation initiation step in mammalian and plant cells. Here, we investigated
      the effect of the three nucleotides immediately upstream of the initiating AUG
      (positions -3 to -1) on the translation efficiency of a reporter gene, beta
      glucuronidase, in dicotyledonous and monocotyledonous plant cells.

PMID- 20129103
TI  - Micropatterning of single myotubes on a thermoresponsive culture surface using
      elastic stencil membranes for single-cell analysis.
AB  - We have developed a micropatterning procedure for single myotubes and
      demonstrated recovery of patterned myotubes without the use of methods that might
      cause damage to the cells. Since skeletal muscle is a highly ordered tissue
      mainly composed of myotubes, analysis of single myotubes is one of the promising
      approaches for studying the various diseases related to skeletal muscle tissues.
      However, the analysis of single myotubes is quite complicated because of the
      difficulty in distinguishing individual myotubes differentiated on a normal cell
      culture surface. In the present study, thin polydimethylsiloxane (PDMS)
      membranes, which have rectangular holes (30, 50, 100, and 200 microm in width;
      500, 750, and 1000 microm in length) through them, were fabricated by using a
      photolithography technique and used for single myotube micropatterning. A bovine
      serum albumin-coated (BSA-coated) stencil membrane was placed on a cell culture
      surface and C2C12 myoblasts were seeded on it. Since the cells could not attach
      to the surface of the stencil membrane, the cell proliferated and differentiated
      into myotubes in the hole areas specifically. By peeling off the membrane, a
      micropattern of myotubes was obtained. It was revealed that the optimum width of
      rectangular holes for a micropattern of single myotubes was between 30 to 50
      microm. Furthermore, by placing a membrane on a thermoresponsive culture surface,
      recovery of the micropatterned myotubes was possible by lowering the temperature.
      This method involving the stencil membranes and a thermoresponsive culture
      surface is useful for analyzing subcellular or single myotubes.

PMID- 20129104
TI  - Albumin production activity of primary rat hepatocytes is improved on type V
      collagen.
AB  - Primary rat hepatocytes were cultured on type V collagen. Hepatocyte spreading on
      type V collagen was inferior compared with that on type I collagen. However, the
      albumin production rates of hepatocytes cultured on type V collagen were
      approximately twice as high as those of hepatocytes cultured on type I collagen.

PMID- 20129105
TI  - Magnetic manipulation device for the optimization of cell processing conditions.
AB  - Variability in human cell phenotypes make it's advancements in optimized cell
      processing necessary for personalized cell therapy. Here we propose a strategy of
      palm-top sized device to assist physically manipulating cells for optimizing cell
      preparations. For the design of such a device, we combined two conventional
      approaches: multi-well plate formatting and magnetic cell handling using
      magnetite cationic liposomes (MCLs). From our previous works, we showed the
      labeling applications of MCL on adhesive cells for various tissue engineering
      approaches. To feasibly transfer cells in multi-well plate, we here evaluated the
      magnetic response of MCL-labeled suspension type cells. The cell handling
      performance of Jurkat cells proved to be faster and more robust compared to MACS
      (Magnetic Cell Sorting) bead methods. To further confirm our strategy, prototype
      palm-top sized device "magnetic manipulation device (MMD)" was designed. In the
      device, the actual cell transportation efficacy of Jurkat cells was satisfying.
      Moreover, as a model of the most distributed clinical cell processing, primary
      peripheral blood mononuclear cells (PBMCs) from different volunteers were
      evaluated. By MMD, individual PBMCs indicated to have optimum Interleukin-2 (IL
      2) concentrations for the expansion. Such huge differences of individual cells
      indicated that MMD, our proposing efficient and self-contained support tool,
      could assist the feasible and cost-effective optimization of cell processing in
      clinical facilities.

PMID- 20129106
TI  - Lactobacillus-mediated RNA interference in nematode.
AB  - We engineered Lactobacillus paracasei to produce a dsRNA that would trigger RNAi
      induced silencing of an essential gene in the nematode Caenorhabditis elegans.
      The dsRNA-expressing L. paracasei can be used in experiments conducted on culture
      plates and may also be used as an orally administrable dsRNA carrier for humans
      and other mammals.

PMID- 20129107
TI  - Droplet-based gene expression analysis using a device with magnetic force-based
      droplet-handling system.
AB  - A droplet-based cell lysis and reverse transcription-polymerase chain reaction
      (PCR) were performed on-chip employing magnetic force-based-droplet-handling
      system. The actuation with a magnet offers a simple system for droplet
      manipulation; it does not need mechanical fluidic systems such as pumps and
      valves for handling solutions. It can be used as a powerful tool for various
      biochemical applications by moving and coalescing sample droplets using magnetic
      beads immersed in mineral oil. The droplet containing magnetic beads and the
      cells were manipulated with the magnet located underneath the channel, and
      coalesced with a droplet of lysis buffer. Using K562 cells as the leukemia model,
      the cell lysis, cDNA synthesis, and amplification of WT1 gene that is known as
      the prognostic factor for acute leukemia were successfully performed from a
      single cell.

PMID- 20129108
TI  - Visualizing "green oil" in live algal cells.
AB  - We report here that BODIPY 505/515, a green lipophilic fluorescent dye, serves as
      an excellent vital stain for the oil-containing lipid bodies of live algal cells.
      BODIPY 505/515 vital staining can be used in combination with fluorescent
      activated cell sorting to detect and isolate algal cells possessing high lipid
      content.

PMID- 20129109
TI  - Quantification and improvement of error rate during ligase detection reaction.
AB  - We estimated the actual error rate during ligase detection reaction (LDR), and
      confirmed that DNA sequences around 3' ends are greatly influenced on the
      specificity of LDR. Its specificity is increased about 1000 times by introducing
      a mismatch base near the 3' ends.

PMID- 20129110
TI  - Abstracts of the World Association of Sleep Medicine 3rd International Congress
      on Sleep Medicine - 12th Brazilian Congress on Sleep Medicine. Sao Paulo, Brazil.
      November 7-11, 2009.

PMID- 20129111
TI  - Season's Greetings.

PMID- 20129112
TI  - Equitable access to regional cardiovascular services.

PMID- 20129113
TI  - Vascular ring: right aortic arch, mirror image branching with Kommerell's
      diverticulum.
AB  - Images of vascular ring-right aortic arch, mirror image branching with
      Kommerell's diverticulum and a brief comment on its management.

PMID- 20129114
TI  - Neurogenic heart disease: from Voodoo to Tako-tsubo.

PMID- 20129115
TI  - Ten year celebration--a decade of progress for Physical Therapy in Sport.

PMID- 20129116
TI  - Bracing does not improve dynamic stability in chronic ankle instability subjects.
AB  - OBJECTIVES: To investigate the effects of an ankle brace on dynamic postural
      stability, measured with Time to Stabilization (TTS), in subjects with chronic
      ankle instability (CAI). DESIGN: Two-within (Condition, Side) repeated measures.
      SETTING: Research laboratory. PARTICIPANTS: Fifteen subjects with unilateral CAI.
      MAIN OUTCOME MEASURES: Subjects participated in two testing sessions during which
      a single-limb jump-landing task was performed with one of two conditions: lace-up
      ankle brace or no ankle brace. Ground reaction forces were used to calculate
      Resultant Vector TTS (RVTTS). RESULTS: For RVTTS, there were no statistically
      significant main effects for Side (F(1,14) = 1.005; p = 0.33) or Condition
      (F(1,14) = 2.48; p = 0.14), as well as no significant interaction effect (F(1,14)
      = 1.67; p = 0.22). CONCLUSION: While TTS is a useful outcome tool for identifying
      deficits in subjects with CAI and improvements related to ankle rehabilitation,
      this measure of dynamic stability does not appear to be sensitive in detecting
      the influence of the application of an ankle brace in this pathological group.
      Researchers need to establish what other testing methods will be the best for
      determining the outcome of the application of an ankle brace in the laboratory
      setting to coincide with the epidemiology data that support the use of these
      devices.

PMID- 20129117
TI  - Shoulder functional ratio in elite junior tennis players.
AB  - OBJECTIVE: To evaluate shoulder rotation strength and compare the functional
      ratio between shoulders of elite junior tennis players. DESIGN: This cross
      sectional study evaluated muscular rotation performance of 40 junior tennis
      players (26 male and 14 female) with an isokinetic dynamometer. MAIN OUTCOME
      MEASURES: Strength variables of external (ER) and internal rotators (IR) in
      concentric and eccentric modes were considered. For the peak torque functional
      ratio, the eccentric strength of the ER and the concentric strength of the IR
      were calculated. RESULTS: All variables related to IR were significantly higher
      on the dominant compared to the non-dominant side in males and females (p<0.05),
      but only boys exhibited this dominance effect in ER (p<0.05 and p<0.001).
      Regarding functional ratios, they were significantly lower for the dominant
      shoulder (p<0.001) and below 1.00 for both groups, indicating that the eccentric
      strength of the ER was not greater than the concentric strength of the IR.
      CONCLUSION: Elite junior tennis players without shoulder injury have shoulder
      rotation muscle strength imbalances that alter the normal functional ratio
      between rotator cuff muscles. Although these differences do not seem to affect
      the athletic performance, detection and prevention with exercise programs at an
      early age are recommended.

PMID- 20129118
TI  - Bilateral difference in hamstrings to quadriceps ratio in healthy males and
      females.
AB  - OBJECTIVE: To compare the isometric and isokinetic hamstrings to quadriceps (H:Q)
      ratio 1) between the dominant (D) and non-dominant (ND) legs, and 2) between
      healthy males and females. DESIGN: Cross-sectional. SETTING: University research
      laboratory. Quadriceps and hamstrings strength were assessed by maximum isometric
      contractions at six angles (40 degrees, 50 degrees, 60 degrees, 70 degrees, 80
      degrees, 90 degrees) and concentric contractions at three angular velocities (60
      degrees s(-1), 180 degrees s(-1), 300 degrees s(-1)). PARTICIPANTS: Forty
      physically active adults (25 males). MAIN OUTCOME MEASURES: Peak isometric and
      isokinetic torques of the quadriceps and hamstrings, and the corresponding H:Q
      ratios. RESULTS: Isometric H:Q ratio increased with greater knee extension
      (P<0.001), with overall a higher ratio in the D leg (P<0.001). Isokinetic H:Q
      ratio increased with angular velocity (P<0.001), with a higher ratio in the D leg
      (P<0.05). Neither isometric nor isokinetic H:Q ratios differed between males and
      females. CONCLUSIONS: When setting rehabilitation goals, it may be appropriate to
      adjust the H:Q ratio and leg strength based on the uninvolved leg with
      consideration of leg dominance. Gender-related differences do not explain the
      discrepancy in the literature regarding bilateral differences in the H:Q ratio.
      Other subject characteristics such as age and training may be more relevant.

PMID- 20129119
TI  - Evaluation of shoulder joint position sense in both asymptomatic and
      rehabilitated professional rugby players and matched controls.
AB  - OBJECTIVE: To assess if joint position sense (JPS) in the shoulder differed
      between un-injured rugby players, matched control subjects and previously injured
      rehabilitated rugby players. DESIGN: Mixed design. SETTING: University
      biomechanics laboratory. PARTICIPANTS: 15 asymptomatic professional rugby union
      players, 15 previously injured professional rugby union players, 15 asymptomatic
      matched non-rugby playing controls had their JPS assessed. MAIN OUTCOME MEASURES:
      JPS was assessed using two criterion angles in the 90 degrees shoulder abduction
      position (45 degrees and 80 degrees external rotation). RESULTS: The study found
      a significant difference between groups in error score (p=0.02). The testing
      angle also had a significant effect on error score (p=0.002), with greater error
      scores occurring in the mid range position. CONCLUSION: This study showed rugby
      players to have better JPS than controls, indicating JPS might not be related to
      injury risk. Poor JPS appears to be related to injury, players having sustained
      an injury have decreased JPS despite surgery and/or rehabilitation and returning
      to sport without incident.

PMID- 20129120
TI  - A preliminary development of the Re-Injury Anxiety Inventory (RIAI).
AB  - OBJECTIVES: The present paper outlines the initial development of an instrument
      to measure re-injury anxiety. METHODS: Face, content and factorial validity were
      examined over three stages of exploratory factor analyses. PARTICIPANTS: 248
      injured sport participants completed the scale. RESULTS: A 28-item measure was
      produced to measure re-injury anxiety, comprising of two factors: re-injury
      anxieties regarding rehabilitation (RIA-R: 15 items) and re-injury anxieties
      regarding returning to training/competition (RIA-RE: 13 items). These two factors
      accounted for 80.56% of the total variance. The internal consistency for both
      factors was above the .70 criterion value; rehabilitation re-injury anxiety
      (alpha=.98); re-entry into competition re-injury anxiety (alpha=.96).
      CONCLUSIONS: Future research needs to test the proposed 2-factor model presented
      in the current research using confirmatory factor analysis.

PMID- 20129121
TI  - Medial contact and smaller plantar loads characterize individuals with
      Patellofemoral Pain Syndrome during stair descent.
AB  - OBJECTIVES: To investigate plantar pressure distribution in individuals with and
      without Patellofemoral Pain Syndrome during the support phase of stair descent.
      DESIGN: Observational case-control study. PARTICIPANTS: 30 young adults with
      Patellofemoral Pain Syndrome and 44 matched controls. MAIN OUTCOME MEASURES:
      Contact area, peak pressure and pressure-time integral (Novel Pedar-X system)
      were evaluated in six plantar areas (medial, central and lateral rearfoot;
      midfoot; medial and lateral forefoot) during stair descent. RESULTS: Contact area
      was greater in the Patellofemoral Pain Syndrome Group at medial rearfoot (p =
      0.019) and midfoot (p < 0.001). Subjects with Patellofemoral Pain Syndrome
      presented smaller peak pressures (p < 0.001). CONCLUSION: The pattern of plantar
      pressure distribution during stair descent in Patellofemoral Pain Syndrome
      subjects was different from controls. This seems to be related to greater medial
      rearfoot and midfoot support. Smaller plantar loads found in Patellofemoral Pain
      Syndrome subjects during stair descent reveal a more cautious motor pattern in a
      challenging task.

PMID- 20129122
TI  - More woes for UK cancer services.

PMID- 20129123
TI  - Rash conclusions from a phase 3 study of cetuximab?

PMID- 20129124
TI  - Targeted therapy for biliary-tract cancer.

PMID- 20129125
TI  - The Lancet Oncology to publish more research in 2010.

PMID- 20129126
TI  - Autosomal-dominant inheritance of hyperphosphorylated paratarg-7.

PMID- 20129127
TI  - Whole-brain radiation therapy in melanoma: an open question.

PMID- 20129129
TI  - Acupuncture.

PMID- 20129130
TI  - Population-based differences in treatment outcome following anticancer drug
      therapies.
AB  - Population-based differences in toxicity and clinical outcome following treatment
      with anticancer drugs have an important effect on oncology practice and drug
      development. These differences arise from complex interactions between biological
      and environmental factors, which include genetic diversity affecting drug
      metabolism and the expression of drug targets, variations in tumour biology and
      host physiology, socioeconomic disparities, and regional preferences in treatment
      standards. Some well-known examples include the high prevalence of activating
      epidermal growth factor receptor (EGFR) mutations in pulmonary adenocarcinoma
      among northeast (China, Japan, Korea) and parts of southeast Asia (excluding
      India) non-smokers, which predict sensitivity to EGFR kinase inhibitors, and the
      sharp contrast between Japan and the west in the management and survival outcome
      of gastric cancer. This review is a critical overview of population-based
      differences in the four most prevalent cancers in the world: lung, breast,
      colorectal, and stomach cancer. Particular attention is given to the clinical
      relevance of such knowledge in terms of the individualisation of drug therapy and
      in the design of clinical trials.

PMID- 20129131
TI  - Evidence-based organ-sparing radiotherapy in head and neck cancer.
AB  - Intensification of radiotherapy treatment for locally advanced head and neck
      cancer by use of altered fractionation schedules or concomitant chemotherapy has
      resulted in substantially improved locoregional control and survival. However,
      these improvements have come at the cost of increased acute, and late, toxic
      effects. The application of technological advances, such as intensity-modulated
      radiotherapy, is expected to further improve the therapeutic index of
      radiotherapy for head and neck cancer, by limiting toxicity and possibly by
      increasing locoregional control. However, the organ-sparing potential of such
      highly conformal radiotherapy techniques relies heavily on the appropriate
      selection and accurate delineation of the crucial organs at risk, with the
      application of rigorous dose constraints during planning. Because xerostomia and
      dysphagia are the main causes of decreased quality of life after radiotherapy for
      head and neck cancer, the prevention of these two complications will form the
      focus of this review.

PMID- 20129132
TI  - Use of new imaging techniques to predict tumour response to therapy.
AB  - Imaging of tumour response to therapy has steadily evolved over the past few
      years as a result of advances in existing imaging modalities and the introduction
      of new functional techniques. The use of imaging as an early surrogate biomarker
      of response is appealing, because it might allow for a window of opportunity
      during which treatment regimens can be tailored accordingly, depending on the
      expected response. The clinical effect of this would ultimately result in a
      reduction in morbidity and undue costs. The aim of this review is to describe the
      potential of various new imaging techniques as biomarkers of early tumour
      response. We have reviewed the literature and identified studies that have
      assessed these techniques, such as diffusion-weighted MRI, dynamic contrast
      enhanced MRI, magnetic resonance spectroscopy, and 18-fluorodeoxyglucose-PET as
      early response indicators, and highlight the current clinical awareness of their
      use.

PMID- 20129133
TI  - RBMOnline in new livery.

PMID- 20129134
TI  - Effect of insulin on oogenesis from mouse fetal germ cells in a serum-free 3D
      culture system.
AB  - Continuous exposure of oocytes to elevated concentrations of insulin compromises
      embryonic developmental competence. However, the effects of insulin on oogenesis
      from fetal germ cells are unknown. The objective of this study was to assess the
      effect of continuous insulin exposure, with or without FSH, on oogenesis and
      follicular development. A simple and efficient method was established that could
      be used to obtain oocytes from pre-meiotic germ cells in 12.5days post-coitum
      (dpc) fetal mouse ovaries using a three-dimensional culture system with serum
      free medium. Mouse 12.5dpc fetal ovaries were cultured for 14days with or without
      insulin/FSH. Low (0.2-1microg/ml) or high (5-20microg/ml) doses of insulin
      retarded oocyte growth in vitro. Insulin at 5microg/ml led to significant oocyte
      growth retardation (P<0.05), while FSH alleviated the deleterious effect of
      insulin. Most importantly, the proportion of secondary follicles at 12days post
      culture in the presence of insulin was reduced significantly compared with
      controls (P<0.05). Expression levels of genes specific for ovarian cells, e.g.
      Cx37, Cx43, Scp3, Bax and FSHR, were significantly reduced when exposed to
      insulin during oogenesis (P<0.05). The data suggest that insulin has a profound
      detrimental effect on oogenesis and folliculogenesis in vitro.

PMID- 20129135
TI  - Ethanol sclerotherapy for ovarian endometriomas before ovarian stimulation.

PMID- 20129140
TI  - Moving away from neglect.

PMID- 20129141
TI  - Stimulating antibiotic development.

PMID- 20129142
TI  - Mandatory influenza immunisation of health-care workers.

PMID- 20129143
TI  - A different view of HIV/AIDS-relief funds in Mozambique.

PMID- 20129145
TI  - Taking cholera seriously.

PMID- 20129146
TI  - Characteristics and outcomes of public campaigns aimed at improving the use of
      antibiotics in outpatients in high-income countries.
AB  - The worldwide increase in resistance to antimicrobial drugs has made reducing the
      unnecessary use of antibiotics a public health priority. There have been
      campaigns in many countries to educate the public about appropriate use of
      antibiotics in outpatients. By use of a comprehensive search strategy and
      structured interviews, we were able to identify and review the characteristics
      and outcomes of 22 campaigns done at a national or regional level in high-income
      countries between 1990 and 2007. The intensity of the campaigns varied widely,
      from simple internet to expensive mass-media campaigns. All but one campaign
      targeted the public and physicians simultaneously. Most campaigns that were
      formally evaluated seemed to reduce antibiotic use. The effect on resistance to
      antimicrobial drugs cannot be assessed accurately at present. Although the most
      effective interventions and potential adverse outcomes remain unclear, public
      campaigns can probably contribute to more careful use of antibiotics in
      outpatients, at least in high-prescribing countries.

PMID- 20129147
TI  - Acute bacterial meningitis in infants and children.
AB  - Bacterial meningitis continues to be an important cause of mortality and
      morbidity in neonates and children throughout the world. The introduction of the
      protein conjugate vaccines against Haemophilus influenzae type b, Streptococcus
      pneumoniae, and Neisseria meningitidis has changed the epidemiology of bacterial
      meningitis. Suspected bacterial meningitis is a medical emergency and needs
      empirical antimicrobial treatment without delay, but recognition of pathogens
      with increasing resistance to antimicrobial drugs is an important factor in the
      selection of empirical antimicrobial regimens. At present, strategies to prevent
      and treat bacterial meningitis are compromised by incomplete understanding of the
      pathogenesis. Further research on meningitis pathogenesis is thus needed. This
      Review summarises information on the epidemiology, pathogenesis, new diagnostic
      methods, empirical antimicrobial regimens, and adjunctive treatment of acute
      bacterial meningitis in infants and children.

PMID- 20129148
TI  - Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum
      beta-lactamase producing, Enterobacteriaceae infections: a systematic review.
AB  - Rising rates of resistance to antimicrobial drugs among Enterobacteriaceae limit
      the choice of reliably active forms of these drugs. We evaluated the evidence on
      fosfomycin as a treatment option for infections caused by members of the family
      Enterobacteriaceae with advanced resistance to antimicrobial drugs, including
      producers of extended-spectrum beta-lactamase (ESBL). We systematically reviewed
      studies evaluating the antimicrobial activity, or the clinical effectiveness of
      fosfomycin. 17 antimicrobial-susceptibility studies were found and included in
      our Review, accounting for 5057 clinical isolates of Enterobacteriaceae with
      advanced resistance to antimicrobial drugs (4448 were producers of ESBL); 11 of
      the 17 studies reported that at least 90% of the isolates were susceptible to
      fosfomycin. Using a provisional minimum inhibitory concentration susceptibility
      breakpoint of 64 mg/L or less, 1604 (96.8%) of 1657 Escherichia coli isolates
      producing ESBL were susceptible to fosfomycin. Similarly, 608 (81.3%) of 748
      Klebsiella pneumoniae isolates producing ESBL were susceptible to fosfomycin. In
      two clinical studies, oral treatment with fosfomycin-trometamol was clinically
      effective against complicated or uncomplicated lower urinary tract infections
      caused by ESBL-producing E coli in, cumulatively, 75 (93.8%) of the 80 patients
      evaluated. Initial clinical data support the use of fosfomycin for the treatment
      of urinary tract infections caused by these pathogens, although further research
      is needed.

PMID- 20129149
TI  - Host immunity as a determinant of treatment outcome in Plasmodium falciparum
      malaria.
AB  - Host immunity is an important but poorly understood determinant of antimalarial
      efficacy, influencing the outcome of prevention and treatment trials. Variations
      in host immunity might explain why factors such as host genetics, age, pregnancy,
      infection with HIV, parasite density, and malaria transmission intensity, can
      raise or lower apparent cure rates. Recently, attempts have been made to
      characterise immunological correlates of treatment outcome in Plasmodium
      falciparum malaria, but not yet for Plasmodium vivax. A better understanding of
      such correlates might improve trials of antimalarial drugs and provide leads for
      vaccine development. Greater understanding of the relation between host immunity
      and treatment outcome is crucial to making informed choices about the use of safe
      but partly effective drugs for malaria prevention in children and pregnant women.
      With increasing malaria control efforts worldwide, declining population immunity
      might alter drug response profiles. Improved methods for assessing antimalarial
      immunity will strengthen malaria control efforts.

PMID- 20129150
TI  - Diagnosis and management of antiretroviral-therapy failure in resource-limited
      settings in sub-Saharan Africa: challenges and perspectives.
AB  - Despite the enormous progress made in scaling up antiretroviral therapy (ART) in
      sub-Saharan Africa, many challenges remain, not least of which are the
      identification and management of patients who have failed first-line therapy.
      Less than 3% of patients are receiving second-line treatment at present, whereas
      15-25% of patients have detectable viral loads 12 months or more into treatment,
      of whom a substantial proportion might have virological failure. We discuss the
      reasons why virological ART failure is likely to be under-diagnosed in the
      routine health system, and address the current difficulties with standard
      recommended second-line ART regimens. The development of new diagnostic tools for
      ART failure, in particular a point-of-care HIV viral-load test, combined with
      simple and inexpensive second-line therapy, such as boosted protease-inhibitor
      monotherapy, could revolutionise the management of ART failure in resource
      limited settings.

PMID- 20129151
TI  - Giant grains of nocardia actinomycetoma.

PMID- 20129158
TI  - Stroke prevention: getting to the heart of the matter.

PMID- 20129159
TI  - Bapineuzumab in Alzheimer's disease: where now?

PMID- 20129160
TI  - Shaking the genome: new studies reveal genetic risk for Parkinson's disease.

PMID- 20129161
TI  - Assessment of neurological and behavioural function: the NIH Toolbox.

PMID- 20129163
TI  - Prognostic predictors for outcome after childhood stroke.

PMID- 20129164
TI  - Surveillance of H1N1-related neurological complications.

PMID- 20129165
TI  - Testing times for clinical research.

PMID- 20129166
TI  - Gordon Wilcock: taking risks to improve Alzheimer's care.

PMID- 20129168
TI  - Current approaches to the diagnosis and management of paediatric migraine.
AB  - Headache is a common complaint in childhood with up to 75% of children reporting
      a notable headache by the age of 15 years. Paediatric migraine is the most
      frequent recurrent headache, occurring in up to 28% of older teenagers. Migraine
      can have a substantial effect on the life of the child, as well as their family,
      leading to lost school days and withdrawal from social interactions. Early
      recognition can lead to successful treatment, improved outcome, and reduced
      disability. The treatment strategy needs to be multipronged and can include acute
      therapy (which can vary depending on the severity of the headache), preventive
      therapy (when the headaches are frequent or causing substantial disability), and
      biobehavioural therapy (to assist with coping with recurrent headaches).
      Additional factors can contribute to exacerbations of headaches, including
      comorbid disorders and pubertal changes, which might lead to the development of
      menstrual migraine. When all these factors are effectively managed, there should
      be an improvement in long-term outcome and prevention of disease progression.

PMID- 20129169
TI  - Transient global amnesia: functional anatomy and clinical implications.
AB  - More than 50 years after its initial description, transient global amnesia (TGA)
      remains one of the most enigmatic syndromes in clinical neurology. Recent MRI
      data suggest that a transient perturbation of hippocampal function is the
      functional correlate of TGA because focal diffusion lesions can be selectively
      detected in the CA1 field of the hippocampal cornu ammonis. Although various
      factors, such as migraine, focal ischaemia, venous flow abnormalities, and
      epileptic phenomena, have been suggested to be involved in the pathophysiology of
      TGA, the factors triggering the emergence of these lesions are still elusive.
      Recent data suggest that the vulnerability of CA1 neurons to metabolic stress
      plays a pivotal part in the pathophysiological cascade, leading to an impairment
      of hippocampal function during TGA. In this Review, we discuss clinical aspects,
      new imaging findings, and recent clinical-epidemiological data with regard to the
      phenotype, functional anatomy, and putative cellular mechanisms of TGA.

PMID- 20129170
TI  - gamma-secretases: from cell biology to therapeutic strategies.
AB  - Presenilins form the catalytic part of the gamma-secretases, protein complexes
      that are responsible for the intramembranous cleavage of transmembrane proteins.
      The presenilins are involved in several biological functions, but are best known
      for their role in the generation of the beta-amyloid (Abeta) peptide in
      Alzheimer's disease and are therefore thought to be important drug targets for
      this disorder. Mutations in the presenilin genes cause early-onset familial
      Alzheimer's disease, but mutation carriers have substantial phenotypic
      heterogeneity. Recent evidence implicating presenilin mutations in non
      Alzheimer's dementias, including frontotemporal dementia and Lewy body dementia,
      warrants further investigation. An increased understanding of the diversity of
      the molecular cell biology of the gamma-secretase complex and the effects of
      clinical mutations in the presenilin genes might help pave the way for improved
      development of drugs that are designed to target gamma-secretase enzymatic
      activity in Alzheimer's disease and potentially in other neurological diseases.

PMID- 20129171
TI  - More biological models and randomised clinical trials.

PMID- 20129172
TI  - The similia principle: results obtained in a cellular model system.
AB  - This paper describes the results of a research program focused on the beneficial
      effect of low dose stress conditions that were applied according to the similia
      principle to cells previously disturbed by more severe stress conditions. In
      first instance, we discuss criteria for research on the similia principle at the
      cellular level. Then, the homologous ('isopathic') approach is reviewed, in which
      the initial (high dose) stress used to disturb cellular physiology and the
      subsequent (low dose) stress are identical. Beneficial effects of low dose stress
      are described in terms of increased cellular survival capacity and at the
      molecular level as an increase in the synthesis of heat shock proteins (hsps).
      Both phenomena reflect a stimulation of the endogenous cellular self-recovery
      capacity. Low dose stress conditions applied in a homologous approach stimulate
      the synthesis of hsps and enhance survival in comparison with stressed cells that
      were incubated in the absence of low dose stress conditions. Thirdly, the
      specificity of the low dose stress condition is described where the initial (high
      dose) stress is different in nature from the subsequently applied (low dose)
      stress; the heterologous or 'heteropathic' approach. The results support the
      similia principle at the cellular level and add to understanding of how low dose
      stress conditions influence the regulatory processes underlying self-recovery. In
      addition, the phenomenon of 'symptom aggravation' which is also observed at the
      cellular level, is discussed in the context of self-recovery. Finally, the
      difference in efficiency between the homologous and the heterologous approach is
      discussed; a perspective is indicated for further research; and the relationship
      between studies on the similia principle and the recently introduced concept of
      'postconditioning hormesis' is emphasized.

PMID- 20129173
TI  - Enzyme stabilization by glass-derived silicates in glass-exposed aqueous
      solutions.
AB  - OBJECTIVES: To analyze the solutes leaching from glass containers into aqueous
      solutions, and to show that these solutes have enzyme activity stabilizing
      effects in very dilute solutions. METHODS: Enzyme assays with acetylcholine
      esterase were used to analyze serially succussed and diluted (SSD) solutions
      prepared in glass and plastic containers. Aqueous SSD preparations starting with
      various solutes, or water alone, were prepared under several conditions, and
      tested for their solute content and their ability to affect enzyme stability in
      dilute solution. RESULTS: We confirm that water acts to dissolve constituents
      from glass vials, and show that the solutes derived from the glass have effects
      on enzymes in the resultant solutions. Enzyme assays demonstrated that enzyme
      stability in purified and deionized water was enhanced in SSD solutions that were
      prepared in glass containers, but not those prepared in plastic. The increased
      enzyme stability could be mimicked in a dose-dependent manner by the addition of
      silicates to the purified, deionized water that enzymes were dissolved in.
      Elemental analyses of SSD water preparations made in glass vials showed that
      boron, silicon, and sodium were present at micromolar concentrations.
      CONCLUSIONS: These results show that silicates and other solutes are present at
      micromolar levels in all glass-exposed solutions, whether pharmaceutical or
      homeopathic in nature. Even though silicates are known to have biological
      activity at higher concentrations, the silicate concentrations we measured in
      homeopathic preparations were too low to account for any purported in vivo
      efficacy, but could potentially influence in vitro biological assays reporting
      homeopathic effects.

PMID- 20129174
TI  - Repetitions of fundamental research models for homeopathically prepared dilutions
      beyond 10(-23): a bibliometric study.
AB  - INTRODUCTION: Repeatability of experiments is an important criterion of modern
      research and a major challenge for homeopathic basic research. There is no recent
      overview about basic research studies in high homeopathic potencies that have
      been subjected to laboratory-internal, multicenter or independent repetition
      trials. METHODS: We considered biochemical, immunological, botanical, cell
      biological and zoological studies on high potencies, i.e. beyond a dilution of
      10(-23). Main sources of information were reviews, personal contact with members
      of the homeopathic basic research community, and the MEDLINE and HOMBREX
      databases. Studies were extracted from the publications and grouped into models.
      Studies were further sorted according to repetition type (laboratory-internal,
      multicenter, or independent) and results achieved. RESULTS: A total of 107
      studies were found. Of these, 30 were initial studies. In the attempt to
      reproduce one of these initial studies, 53 follow-up studies yielded comparable
      effects (35 laboratory-internal, 8 multicenter, 10 independent repetitions),
      eight studies showed a consistent, yet different result from the initial study (2
      laboratory-internal, 2 multicenter, 4 independent repetitions), and 16 studies
      yielded no effects (5 laboratory-internal, 2 multicenter, 9 independent
      repetitions). When all repetitive studies are considered, 69% reported effects
      comparable to that of the initial study, 10% different effects, and 21% no
      effects. Independently performed repetition studies reported 44% comparable
      effects, 17% different effects, and 39% no effects. CONCLUSIONS: We identified 24
      experimental models in basic research on high homeopathic potencies, which were
      repeatedly investigated. 22 models were reproduced with comparable results, 6
      models with different results, and repetition showed no results for 15 models.
      Independent reproductions with either comparable or different results were found
      for seven models. We encourage further repetition trials of published studies, in
      order to learn more about the model systems used and in order to test their
      repeatability.

PMID- 20129175
TI  - Animal models for studying homeopathy and high dilutions: conceptual critical
      review.
AB  - INTRODUCTION: This is a systematic review of the animal models used in studies of
      high dilutions. The objectives are to analyze methodological quality of papers
      and reported results, and to highlight key conceptual aspects of high dilution to
      suggest clues concerning putative mechanisms of action. METHODS: Papers for
      inclusion were identified systematically, from the Pubmed-Medline database, using
      'Homeopathy' and 'Animal' as keywords. Only original full papers in English
      published between January 1999 and June 2009 were included, reviews, scientific
      reports, thesis, older papers, papers extracted from Medline using similar
      keywords, papers about mixed commercial formulas and books were also considered
      for discussion only. 31 papers describing 33 experiments were identified for the
      main analysis and a total of 89 items cited. RESULTS: Systematic analysis of the
      selected papers yielded evidence of some important intrinsic features of high
      dilution studies performed in animal models: a) methodological quality was
      generally adequate, some aspects could be improved; b) convergence between
      results and materia medica is seen in some studies, pointing toward to the
      possibility of systematic study of the Similia principle c) both isopathic and
      Similia models seem useful to understand some complex biological phenomena, such
      as parasite-host interactions; d) the effects of high dilutions seem to stimulate
      restoration of a 'stable state', as seen in several experimental models from both
      descriptive and mathematical points of view.

PMID- 20129176
TI  - Basophil models of homeopathy: a sceptical view.
AB  - This paper examines the activation and inhibition of activation of human
      basophils. After a brief description of human basophils, different methods to
      determine basophil activation are discussed with a special emphasis on the use of
      flow cytometric methods, as these circumvent the potential problems of assays
      based on the loss of colour by activated basophils. The activation of human
      basophils by ultra-high dilutions of anti-IgE is discussed. The majority of the
      paper describes the inhibition of basophil activation by ultra-high dilutions of
      histamine. The results from published papers are described and discussed. After
      over 20 years research trying to find out if high dilutions of histamine have a
      negative feedback effect on the activation of basophils by anti-IgE, what do we
      know? The methods are poorly standardized between laboratories - although the
      same is true for conventional studies. Certainly there appears to be some
      evidence for an effect - albeit small in some cases - with the high dilutions in
      several different laboratories using the flow cytometric methodologies. After
      standardization of a number of parameters, it is recommended that a multi-centre
      trial be performed to hopefully put an end to this "never-ending story".

PMID- 20129177
TI  - Homeopathy as replacement to antibiotics in the case of Escherichia coli
      diarrhoea in neonatal piglets.
AB  - BACKGROUND: The use of antibiotics in the livestock sector is increasing to such
      an extent that it threatens negative consequences for human health, animal health
      and the environment. Homeopathy might be an alternative to antibiotics. It has
      therefore been tested in a randomised placebo-controlled trial to prevent
      Escherichia coli diarrhoea in neonatal piglets. METHOD: On a commercial pig farm
      52 sows of different parities, in their last month of gestation, were treated
      twice a week with either the homeopathic agent Coli 30K or placebo. The 525
      piglets born from these sows were scored for occurrence and duration of
      diarrhoea. RESULTS: Piglets of the homeopathic treated group had significantly
      less E. coli diarrhoea than piglets in the placebo group (P<.0001). Especially
      piglets from first parity sows gave a good response to treatment with Coli 30K.
      The diarrhoea seemed to be less severe in the homeopathically treated litters,
      there was less transmission and duration appeared shorter.

PMID- 20129178
TI  - Chronic primary insomnia: efficacy of homeopathic simillimum.
AB  - INTRODUCTION: Chronic primary insomnia is defined as difficulty in initiating or
      maintaining sleep or of non-restorative sleep that lasts for at least 1 month and
      causes significant distress or impairment in social, occupational or other
      important areas of functioning. The homeopathic simillimum is that remedy which
      most closely corresponds to the totality of symptoms; remedy selection is based
      on a full evaluation of the patient's physical, emotional and mental
      characteristics. AIM/PURPOSE: The purpose of this randomised, double-blind,
      placebo-controlled study was to evaluate the efficacy of homeopathic simillimum
      in the treatment of chronic primary insomnia. METHOD: 30 participants were
      selected in accordance with DSM-IV TR (2000)(1) criterion 307.42 Primary Insomnia
      and then randomly divided between treatment and placebo groups. The measurement
      tools used were a Sleep Diary (SD) and the Sleep Impairment Index (SII).(2) After
      an initial consultation, 2 follow-up consultations at 2-week intervals took
      place. Homeopathic medication was prescribed at the first and second
      consultations. The SII was completed at each consultation and participants were
      instructed at the first consultation to start the SD. RESULTS: SD data revealed
      that verum treatment resulted in a significant increase in duration of sleep
      throughout the study, compared to the placebo treatment which resulted in no
      significant increase in duration of sleep. A significant improvement in SII
      summary scores and number of improved individual questions were found in the
      verum group, responses to all 11 questions having improved significantly upon
      completion of the study. An initial improvement occurred in the placebo group,
      but was not sustained. Comparison of results between the groups revealed a
      statistically significant difference. CONCLUSION: The homeopathic simillimum
      treatment of primary insomnia was effective, compared to placebo. Homeopathy is a
      viable treatment modality for this condition and further research is justified.

PMID- 20129179
TI  - Homeopathic trial design in influenza treatment.
AB  - This review presents a critical evaluation of methodological quality in
      controlled trials on homeopathic treatment of influenza. First, a short summary
      on the prevalence, quality, and most commonly cited shortcomings of homeopathic
      controlled trials in general is presented to support the more specific points
      within influenza trials alone. To this end, three areas of the homeopathic
      literature are examined; large meta-analyses looking at study quality and results
      across research areas, reviews on research within specific diagnostic categories,
      and the available reviews and primary studies on influenza treatment trials. The
      specific methodological designs of homeopathic influenza treatment trials are
      then compared, on a point by point basis, to pharmaceutical trials on influenza
      antiviral drugs. The goal of the evaluation is to highlight frequently cited
      problems in homeopathic trial design, suggest possible improvement for future
      studies, and make specific recommendations for homeopathic influenza trials based
      on a comparison to standard antiviral trials.

PMID- 20129180
TI  - Placebo effect sizes in homeopathic compared to conventional drugs - a systematic
      review of randomised controlled trials.
AB  - BACKGROUND: It has been hypothesised that randomised, placebo-controlled clinical
      trials (RCTs) of classical (individualised) homeopathy often fail because placebo
      effects are substantially higher than in conventional medicine. OBJECTIVES: To
      compare placebo effects in clinical trials on homeopathy to placebo effects on
      trials of conventional medicines. METHODS: We performed a systematic literature
      analysis on placebo-controlled double-blind RCTs on classical homeopathy. Each
      trial was matched to three placebo-controlled double-blind RCTs from conventional
      medicine (mainly pharmacological interventions) involving the same diagnosis.
      Matching criteria included severity of complaints, choice of outcome parameter,
      and treatment duration. Outcome was measured as the percentage change of symptom
      scores from baseline to end of treatment in the placebo group. 35 RCTs on
      classical homeopathy were identified. 10 were excluded because no relevant data
      could be extracted, or less than three matching conventional trials could be
      located. RESULTS: In 13 matched sets the placebo effect in the homeopathic trials
      was larger than the average placebo effect of the conventional trials, in 12
      matched sets it was lower (P=0.39). Additionally, no subgroup analysis yielded
      any significant difference. CONCLUSIONS: Placebo effects in RCTs on classical
      homeopathy did not appear to be larger than placebo effects in conventional
      medicine.

PMID- 20129181
TI  - When sorry seems to be the hardest word: CAM, free speech, and the British legal
      system.

PMID- 20129183
TI  - Pediatric urology. Editorial.

PMID- 20129184
TI  - A focus on health disparities.

PMID- 20129185
TI  - What's our impact?

PMID- 20129186
TI  - Short-term temporal stability in observed retail food characteristics.
AB  - OBJECTIVE: Use of direct observation to characterize neighborhood retail food
      environments is increasing, but to date most studies have relied on a single
      observation. If food availability, prices, and quality vary over short time
      periods, repeated measures may be needed to portray these food characteristics.
      This study evaluated short-term (2-week), within-season temporal stability in
      retail food availability, prices, and quality. DESIGN: In-person observations of
      retail food stores at 2 time points, 2 weeks apart. SETTING: Southwest Chicago,
      IL. SAMPLE: 157 food stores. MAIN OUTCOME MEASURES: Availability and prices of
      food items selected from the following food groups: fruit, vegetables, grains,
      meats and beans, and dairy, as well as fresh produce quality. ANALYSIS: Temporal
      stability was tested for availability using a McNemar test and for price and
      quality using a Wilcoxon signed-rank test. RESULTS: Measures of food availability
      and prices as well as fresh produce quality at stores were generally stable at
      the 2 time points. CONCLUSIONS AND IMPLICATIONS: This study suggests that a
      single observation may be sufficient to accurately characterize within-season
      food availability, food prices, and fresh produce quality.

PMID- 20129187
TI  - Food and personal hygiene perceptions and practices among caregivers whose
      children have diarrhea: a qualitative study of urban mothers in Tangerang,
      Indonesia.
AB  - OBJECTIVE: To examine caregivers' perceptions and practices related to food and
      personal hygiene and its association with diarrhea in children 6 to 36 months of
      age who suffered recurrent diarrhea. DESIGN: This qualitative study, conducted in
      March and April 2006, used both in-depth interviews and direct observation data.
      SETTING: Urban Tangerang, near Jakarta, Indonesia. PARTICIPANTS: Twenty-four
      mothers whose monthly household income was less than $160 US and had latrines in
      their homes. PHENOMENON OF INTEREST: To examine the relationship between mothers'
      perceptions and behaviors related to diarrhea, food hygiene, and personal
      hygiene. ANALYSIS: Interview transcripts were analyzed based on the phenomenon of
      interest and coded for common themes. RESULTS: Mothers differentiated diarrhea
      episodes as either disease or nondisease. Most mothers associated the importance
      of food hygiene with disease prevention, contaminating agents, and health.
      Mothers commonly wiped cutting boards with a kitchen towel after slicing
      vegetables, whereas they washed the board with soap and water after cutting raw
      meat. Mothers perceived that the importance of personal hygiene was for
      maintaining health and cleanliness. The majority of mothers washed their hands
      without soap after performing housework and cooking. CONCLUSIONS AND
      IMPLICATIONS: Improving mothers' knowledge while incorporating existing
      perceptions might lead to positive changes.

PMID- 20129188
TI  - The association between funding for statewide programs and enactment of obesity
      legislation.
AB  - OBJECTIVE: As part of a national effort to prevent and control obesity, the
      Centers for Disease Control and Prevention's (CDC's) Nutrition and Physical
      Activity Program to Prevent Obesity and Other Chronic Diseases (NPAO) provides
      funding to states to improve access to healthful food and increase opportunities
      for physical activity. The CDC also provides funding to states to build
      Coordinated School Health (CSH) programs across agencies and within schools to
      help reduce chronic disease risk factors. This paper investigates the possible
      role of these programs in state policy change. METHODS: Descriptive study of
      state legislation targeting obesity prevention passed in 2005. Units of analysis
      were 135 pieces of obesity-related state legislation identified within 4
      legislative databases. Legislation was coded into programmatic setting and
      obesity-prevention strategy categories. RESULTS: On average, states receiving
      NPAO or CSH program funding passed twice as many bills as states not yet funded.
      CONCLUSIONS AND IMPLICATIONS: The statewide obesity prevention and school health
      programs may have contributed to states enacting more obesity-related
      legislation. Further research into the process by which state programs influence
      the enactment and effective implementation of policies could help build the
      evidence base for policy changes that help prevent obesity.

PMID- 20129189
TI  - The Network for the Enhancement of Endocrinology and Oncology Knowledge: a case
      based consideration of current practice in Cushing's disease and acromegaly.

PMID- 20129190
TI  - Rationale for treatment and therapeutic options in Cushing's disease.
AB  - Cushing's disease results from prolonged overexposure of tissues to endogenous
      glucocorticoids, secondary to adrenocorticotrophin excess from the pituitary.
      Common clinical signs and symptoms include weight gain, hypertension, and
      osteoporosis. Effective treatment of Cushing's disease can normalize biochemical
      levels, reverse comorbidities, and improve overall survival and quality of life.
      Treatment options include pituitary or adrenal surgery, radiotherapy, and various
      medical therapies, but each has important limitations. Medical therapies that
      effectively target the pituitary tumour are urgently needed.

PMID- 20129191
TI  - Diagnostic challenges in acromegaly: a case-based review.
AB  - Acromegaly is a rare, chronic condition caused by sustained and unregulated
      oversecretion of growth hormone (GH), usually attributed to a pituitary adenoma.
      Prolonged exposure to excessive amounts of GH and its target hormone, insulin
      like growth factor-1 (IGF-1), results in pronounced metabolic changes and tissue
      enlargement that ultimately lead to increased morbidity and early mortality. As
      early diagnosis of acromegaly can have substantial beneficial effects on quality
      of life and overall survival for patients, it is important that the tests used to
      diagnose the condition are accurate, with highly reproducible results. The first
      kits used to measure GH and IGF-1 were radioimmunoassay, with many limitations
      that necessitated the development of more sensitive tools. Newer assays, although
      better than previous assays, are far from ideal. Simple changes that may improve
      the testing process include the adoption of mass units for GH interpretation and
      the use of a single recombinant calibrant. Furthermore, the conversion factors
      and reference ranges used to describe the normal limits for GH and IGF-1 levels
      require refinement. Physicians should be aware of the GH and IGF-1 assays used in
      their reference laboratories, and ensure that they know the appropriate assay cut
      off values, to avoid misinterpreting results.

PMID- 20129192
TI  - 5 Long-term acromegaly and associated cardiovascular complications: a case-based
      review.
AB  - Because growth hormone and IGF-1 both have regulatory roles in the cardiovascular
      system, patients with acromegaly often present with abnormalities of heart
      structure and function and the vascular system, which if left unmanaged can
      reduce life expectancy. Early symptoms of acromegalic cardiomyopathy
      (hyperkinetic syndrome) can be characterized by cardiac hypertrophy, increased
      heart rate, and increased systolic output. When left untreated, more pronounced
      hypertrophy, signs of diastolic dysfunction and insufficient systolic function on
      exertion arise, and can lead to systolic dysfunction at rest, and eventually
      heart failure with signs of dilative cardiomyopathy. Increasingly, evidence
      suggests that early diagnosis and treatment of acromegaly (before the age of 40
      years) can help prevent the progression of cardiovascular disease, improve
      quality of life, and reduce the risk of premature mortality. This review focuses
      on management strategies for newly diagnosed patients with acromegaly and
      evidence of cardiovascular disease. The roles of surgery and medical treatment
      are discussed in the context of using optimal treatment strategies to help
      reverse cardiac hypertrophy and normalize other cardiac risk factors.

PMID- 20129194
TI  - Osteoarthritis. Preface.

PMID- 20129193
TI  - Diagnosis/differential diagnosis of Cushing's syndrome: a review of best
      practice.
AB  - Endogenous Cushing's syndrome is an uncommon endocrine disorder that can often
      prove challenging, for both initial diagnosis and subsequent differential
      diagnosis of the underlying cause. Understanding the advantages and pitfalls of
      the diagnostic methods used in Cushing's syndrome is essential for accurate
      diagnosis and differential diagnosis, and guidelines outlining the most
      appropriate approaches have recently been published. We examine how current
      practice guidelines can be used in a real case-based scenario, and review the
      recommended strategies to achieve successful diagnosis and differential
      diagnosis.

PMID- 20129195
TI  - The clinical relevance of genetic susceptibility to osteoarthritis.
AB  - Osteoarthritis is a major musculoskeletal cause of disability in the elderly, but
      current therapeutic approaches are insufficient to prevent initiation and
      progression of the disease. Genetic studies in humans have identified molecules
      involved in signalling cascades that are important for the pathology of the joint
      components. These include the bone morphogenetic protein (BMP) signalling, the
      wingless-type signalling and the thyroid pathway as well as apoptotic-related
      molecules. There is emerging evidence indicating that inflammatory molecules
      related to cytokine production, prostaglandin and arachidonic acid metabolism are
      also involved in susceptibility to osteoarthritis. All of these pathways are
      likely targets for pharmacological intervention. Genetic variation also affects
      pain due to osteoarthritis highlighting molecular mechanisms for pain relief.
      Moreover, combinations of genetic markers can be used to identify individuals at
      high risk of osteoarthritis and risk of total joint arthroplasty failure, which
      should facilitate the application of preventive and disease management
      strategies.

PMID- 20129197
TI  - Imaging the joint in osteoarthritis: a place for ultrasound?
AB  - Ultrasound (US) is a valuable tool for imaging musculoskeletal changes in
      osteoarthritis. It shows early and late findings related to inflammation and
      structural damage. Sonography is a safe tool, which has recently registered an
      increasing and widespread use, it being considered as a bedside procedure in the
      clinical assessment of rheumatic patients. Its applications in osteoarthritis are
      related to easy accessibility of equipment, low cost, short duration of single
      examinations and the possibility of performing a multiregional joint evaluation
      in the same scanning session. Permitting an extensive evaluation of most joint
      changes present in osteoarthritis, it gives the opportunity to monitor disease
      progression and perform a follow-up of the response to different local and
      systemic treatments. US-guided procedures are commonly performed with safety,
      reliability and optimal patient tolerance. Development in technology and
      technique with improvement of new research studies will further amplify the
      diagnostic role of ultrasound in osteoarthritis in the near future.

PMID- 20129196
TI  - Why is osteoarthritis an age-related disease?
AB  - Although older age is the greatest risk factor for osteoarthritis (OA), OA is not
      an inevitable consequence of growing old. Radiographic changes of OA,
      particularly osteophytes, are common in the aged population, but symptoms of
      joint pain may be independent of radiographic severity in many older adults.
      Ageing changes in the musculoskeletal system increase the propensity to OA but
      the joints affected and the severity of disease are most closely related to other
      OA risk factors such as joint injury, obesity, genetics and anatomical factors
      that affect joint mechanics. The ageing changes in joint tissues that contribute
      to the development of OA include cell senescence that results in development of
      the senescent secretory phenotype and ageing changes in the matrix including
      formation of advanced glycation end-products that affect the mechanical
      properties of joint tissues. An improved mechanistic understanding of joint
      ageing will likely reveal new therapeutic targets to slow or halt disease
      progression. The ability to slow progression of OA in older adults will have
      enormous public health implications given the ageing of our population and the
      increase in other OA risk factors such as obesity.

PMID- 20129198
TI  - The role of biomechanics in the initiation and progression of OA of the knee.
AB  - The knee is one of the most common joints affected by osteoarthritis (OA),
      frequently with clinical presentation by middle age or even earlier. Accumulating
      evidence supports that knee OA progression is often driven by biomechanical
      forces, and the pathological response of tissues to such forces leads to
      structural joint deterioration, knee symptoms and reduced function. Well-known
      biomechanical risk factors for progression include joint malalignment and
      meniscal tear. The high risk of OA after knee injury demonstrates the critical
      role of biomechanical factors also in incident disease in susceptible
      individuals. However, our knowledge of the contributing biomechanical mechanisms
      in the development of early disease and their order of significance is limited.
      Part of the problem is our current lack of understanding of early-stage OA, when
      it starts and how to define it.

PMID- 20129199
TI  - Arthroscopy as a treatment for knee osteoarthritis.
AB  - Since surfaces become irregular and debris from cartilage and meniscus gets
      released into the joint cavity of osteoarthritic joints, washing away this debris
      and attendant crystals, smoothing rough surfaces and repairing tears might help
      patients with disease. Such interventions are accomplished during an arthroscopy,
      when a fibre-optic endoscope and surgical instruments are inserted into the knee.
      While initial uncontrolled case series suggested that arthroscopy alleviated pain
      in patients with osteoarthritis, large randomised trials have suggested that
      arthroscopy has a limited role as a treatment of osteoarthritis.

PMID- 20129201
TI  - Targeting the synovial tissue for treating osteoarthritis (OA): where is the
      evidence?
AB  - Osteoarthritis (OA) is often a progressive and disabling disease, which occurs in
      the setting of a variety of risk factors--such as advancing age, obesity and
      trauma--that collude to incite a cascade of pathophysiological events within
      joint tissues. An important emerging theme in OA is a broadening of focus from a
      disease of cartilage to one of the 'whole joint.' The synovium, bone and
      cartilage are each involved in pathological processes that lead to progressive
      joint degeneration. Additional themes that have emerged over the past decade are
      novel mechanisms of cartilage degradation and repair, the relationship between
      biomechanics and biochemical pathways, the importance of inflammation and the
      role of genetics. In this article, we review the molecular, clinical and imaging
      evidence that synovitis is not an 'incidental finding of OA', but plays a
      significant role in disease pathogenesis, and could therefore represent a target
      for future treatments.

PMID- 20129200
TI  - Targeting subchondral bone for treating osteoarthritis: what is the evidence?
AB  - Over the past few decades, significant progress has been made with respect to new
      concepts about the pathogenesis of osteoarthritis (OA). This article summarises
      some of the knowledge we have today on the involvement of the subchondral bone in
      OA. It provides substantial evidence that changes in the metabolism of the
      subchondral bone are an integral part of the OA disease process and that these
      alterations are not merely secondary manifestations, but are part of a more
      active component of the disease. Thus, a strong rationale exists for therapeutic
      approaches that target subchondral bone resorption and/or formation, and data
      evaluating the drugs targeting bone remodelling raise the hope that new treatment
      options for OA may become available.

PMID- 20129202
TI  - What are the best markers for disease progression in osteoarthritis (OA)?
AB  - To be able to prevent progression of osteoarthritis, the knowledge of prognostic
      factors of this progression is important. If certain prognostic factors are
      modifiable, they may enhance our ability to reduce osteoarthritis progression.
      Even if these prognostic factors are not modifiable, they can still be used to
      identify high-risk groups, which may have implications for patient information
      and the perspective of medical treatment. Prognostic factors of progression are
      reviewed here, mainly for hip and knee osteoarthritis as most data available
      concern these localisations. Areas of further research are highlighted.

PMID- 20129203
TI  - Non-pharmacological approaches for the treatment of osteoarthritis.
AB  - For the most part, non-pharmacological approaches are recommended for
      osteoarthritis treatment. This recommendation is based mainly on biomechanical
      observations leading to a modulation of the symptomatic loading joint. Approaches
      include orthoses, insoles, exercise, diet and patient education. The approach
      used for each osteoarthritis site must be adapted for the individual patient.
      Here, we use an evidence-based approach, including the European League Against
      Rheumatism (EULAR) and Osteoarthritis Research Society International (OARSI)
      recommendations, to summarise the non-pharmacological treatments available for
      knee, hip and hand osteoarthritis and to help the physician in daily clinical
      practice.

PMID- 20129204
TI  - Targeted therapies in osteoarthritis: a systematic review of the trials on
      www.clinicaltrials.gov.
AB  - A systematic review of the clinical trials in osteoarthritis registered on the
      public website of the Clinical Trials Data Bank at the National Institutes of
      Health (NIH) has been performed. Such a review should cover the majority of the
      ongoing or forthcoming trials in the disease. This review focusses on trials
      designed to test safety and/or efficacy of targeted therapies in osteoarthritis.

PMID- 20129205
TI  - Developing a minimum standard of care for treating people with osteoarthritis of
      the hip and knee.
AB  - We reviewed three recently published guidelines for the management of
      osteoarthritis (OA) and considered the evidence and potential for implementation.
      From this we propose a minimum standard of care, or a 'core set' of
      interventions, that should be offered to all patients with OA of the hip and/or
      knee. Eight core recommendations emerged where it is recommended that health-care
      professionals: Provide advice about, and offer access to appropriate information
      for OA self-management and lifestyle change; Provide advice about weight loss if
      patient is overweight or obese and refer to services as required; Provide advice
      for land-based exercises incorporating aerobic and strengthening components and
      refer to services as required; Recommend adequate paracetamol for pain relief;
      Make patients aware that non-steroid anti-inflammatory drugs (NSAIDs) or coxibs
      can improve symptoms in majority but this comes with potential for harm and that
      risk potential varies--be aware of and minimise the individual's risk potential;
      Offer intra-articular steroids for short-term relief of a flare or acute
      deterioration in symptoms; Offer stronger analgesic relief if prolonged severe
      symptoms; Offer access to assessment for arthroplasty for consumers with severe
      symptomatic OA not responding to conservative therapy. An integrated, chronic
      disease model of care is proposed to best implement OA management and a check
      list of clinical indicators/performance measures is provided.

PMID- 20129206
TI  - Early detection of cognitive impairment: do screening tests help?

PMID- 20129207
TI  - Home care for dying people.

PMID- 20129208
TI  - Disparities between preferences and practice for end-of-life care.

PMID- 20129209
TI  - H1N1 influenza in elderly nursing home residents.
AB  - We offer this brief report to inform other nursing home medical directors and
      attending physicians of a possible change in the profile of persons susceptible
      to H1N1 influenza. If a significant number of cases appear in older persons, the
      recommendations for H1N1 vaccination may need to be changed to include the
      elderly.

PMID- 20129210
TI  - How to improve nutritional support in geriatric institutions.
AB  - Nutritional problems are frequent in nursing homes including undernutrition,
      obesity, and diabetes mellitus, mainly related to disability and behavior
      troubles. Adequate nutritional care relies both on the quality of menus for
      regular and modified diet (texture-modified and enriched food) and on the staff
      knowledge of nutritional problems, particularly undernutrition. Self-assessment
      of professional practices for all staff categories that are involved in this area
      can be used to increase training of staff and quality of nutritional care.

PMID- 20129211
TI  - Home care in the last year of life: family member perceptions of unmet need
      associated with last place of care.
AB  - OBJECTIVE: To examine the association of family members' perception about the
      adequacy of home health services at the last place of care before death. DESIGN:
      Retrospective cross-sectional study. Mortality follow-back survey by telephone
      interview. SETTING: Home health services. PARTICIPANTS: Bereaved family members
      or knowledgeable informants of deceased persons in 22 states. MEASUREMENTS: Proxy
      perception of need of home health care during the last 12 months of decedent's
      life, whether the amount of care received was enough, and last place of care (ie,
      where the person spent at least 48 hours nearest to the time of death). RESULTS:
      Of the 1578 interviews, 622 informants reported that decedents needed home health
      care in the last year of life. Among decedents needing home health care, 144
      informants reported that the home health services provided did not meet their
      needs. After adjusting for age, gender, insurance, education, race, cause of
      death, functional status, and place of residence, decedents reported as not
      receiving enough home health care were 1.8 (95% CI 1.1-2.9) times more likely to
      die in a nursing home. CONCLUSION: The perception that home health services
      before death did not meet the decedent's needs may contribute to greater nursing
      home use.

PMID- 20129212
TI  - ACE-inhibition and physical function: results from the Trial of Angiotensin
      Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study.
AB  - OBJECTIVES: Aim of the present study was to evaluate whether an ACE inhibitor
      intervention is able to significantly improve physical performance and muscle
      strength in a sample of older persons. DESIGN: Double-blind, cross-over,
      randomized, placebo-controlled trial. SETTING: The Trial of Angiotensin
      Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study.
      PARTICIPANTS: Participants were 257 subjects aged 55 years and older with high
      cardiovascular risk profile. INTERVENTION: Six months of fosinopril use versus
      placebo. MEASUREMENTS: The Short Physical Performance Battery score (rescaled to
      obtain a continuous variable ranging from 0 to 3 points), and the hand grip
      strength were measured at the baseline visit, and after 6 and 12 months of follow
      up. Paired t test analyses were performed to compare results of physical function
      measures after ACE inhibition and placebo interventions. RESULTS: Mean age of the
      sample population was 65.97 (standard deviation 7.41) years old. No statistically
      significant difference was found at the Short Physical Performance Battery
      (P=.23) and hand grip strength (P=.57) results after ACE inhibition (2.113,
      standard deviation [SD] 0.284; and 37.044 kg, SD 12.993 kg, respectively)
      compared to placebo (2.096, SD 0.298; and 36.898 kg, SD 13.178 kg, respectively).
      No significant effects from ACE inhibition were also found when the 3 subtests
      composing the Short Physical Performance Battery (ie, 4-meter walking speed,
      balance, and chair stand tests) were separately analyzed. Consistent negative
      results were obtained after analyses were restricted to participants showing the
      highest compliance to treatment and/or receiving the maximum fosinopril dosage.
      CONCLUSION: No significant modifications in physical performance and muscle
      strength were reported after 6 months of fosinopril use in older persons with
      high cardiovascular risk profile. Given these negative findings, it is possible
      that the beneficial effects of ACE inhibitors on physical function might be
      attributable to the activation of a virtuous cycle determined by an improved
      cardiovascular system. Further specifically designed studies are needed to
      confirm our findings, and expand them to different populations and ACE
      inhibitors. If our findings will be confirmed, the extracardiovascular properties
      of ACE inhibitors in older persons might be substantially resized.

PMID- 20129213
TI  - Prevalence and severity of chronic kidney disease and anemia in the nursing home
      population.
AB  - OBJECTIVES: Chronic kidney disease (CKD) is an emerging health concern and may
      have important implications for the management of older people with many other
      chronic conditions, such as the nursing home (NH) resident population. This study
      was designed to describe the prevalence of CKD and associated comorbidities in a
      representative sample of NH residents. DESIGN: Cross-sectional descriptive study
      as a component of a prospective observational study of CKD and anemia in the NH
      population. SETTING: Eighty-two geographically representative NHs in the United
      States. PARTICIPANTS: Participants were 794 NH residents who had complete
      baseline data collected. MEASUREMENTS: Residents for whom consent was obtained
      underwent a record review focused on identifying a predefined set of comorbid
      conditions, clinical assessment, and blood and urine collections. Stage of CKD
      was based on estimated GFR (eGFR) using the MDRD equation: no CKD (eGFR > 60
      mL/min/1.73 m(2)), Stage 3a (45-59), Stage 3b (30-44), and Stage 4/5 (< 30).
      RESULTS: Consent was obtained from 847 of 1626 residents screened; 32 were
      ineligible and 21 dropped out of the study; complete data were available for 794
      residents. CKD was present in approximately 50% of residents; of these residents
      with CKD, 47.6% were stage 3a, 39.27% stage 3b, and 13.2% stage 4/5. Fifty
      percent of the population had anemia, and anemia was more common in those with
      CKD. The average number of comorbid conditions in the population was 5.3 (SD
      2.2); the proportion of patients with multiple comorbid conditions, especially
      cardiovascular conditions, increased with increasing stage of CKD. Among those
      without CKD, 57% had 5 or more comorbidities in comparison to 87% of those with
      stage 4/5 CKD. CONCLUSIONS: In this representative sample of 794 US NH residents,
      50% had clinical evidence of CKD. Patients with CKD, particularly those at later
      stages, were more likely to have cardiovascular comorbidities and anemia. The co
      occurrence of these conditions in institutionalized populations may have
      important implications for the clinical management of this patient population,
      particularly as it relates to the potential for further renal complications.

PMID- 20129214
TI  - Preferences versus practice: life-sustaining treatments in last months of life in
      long-term care.
AB  - PURPOSE: To determine prevalence and correlates of decisions made about specific
      life-sustaining treatments (LSTs) among residents in long-term care (LTC)
      settings, including characteristics associated with having an LST performed when
      the resident reportedly did not desire the LST. DESIGN AND PARTICIPANTS: After
      death interviews with 1 family caregiver and 1 staff caregiver for each of 327
      LTC residents who died in the facility. SETTING: The setting included 27 nursing
      homes (NHs) and 85 residential care/assisted living (RC/AL) settings in 4 states.
      MEASUREMENTS: Decedent demographics, facility characteristics, prevalence of
      decisions made about specific LSTs, percentage of time LSTs were performed when
      reportedly not desired, and characteristics associated with that. RESULTS: Most
      family caregivers reported making a decision with a physician about resuscitation
      (89.1%), inserting a feeding tube (82.1%), administering antibiotics (64.3%), and
      hospital transfer (83.7%). Reported care was inconsistent with decisions made in
      5 of 7 (71.4%) resuscitations, 1 of 7 feeding tube insertions (14.3%), 15 of 78
      antibiotics courses (19.2%), and 26 of 87 hospital transfers (29.9%). Decedents
      who received antibiotics contrary to their wishes were older (mean age 92 versus
      85, P=.014). More than half (53.8%) of decedents who had care discordant with
      their wishes about hospitalization lived in a NH compared with 32.8% of those
      whose decisions were concordant (P=.034). CONCLUSION: Most respondents reported
      decision making with a doctor about life-sustaining treatments, but those
      decisions were not consistently heeded. Being older and living in a NH were risk
      factors for decisions not being heeded.

PMID- 20129215
TI  - Predictors of in-hospital mortality among hospitalized nursing home residents: an
      analysis of the National Hospital Discharge Surveys 2005-2006.
AB  - OBJECTIVE: To determine the demographic and clinical predictors of in-hospital
      mortality among hospitalized nursing home (NH) residents. DESIGN: Retrospective
      analysis of the public-use copies of the 2005-2006 National Hospital Discharge
      Survey (NHDS) datasets. SETTING: Non-federal acute-care, short-stay hospitals in
      all 50 states and the District of Columbia. PARTICIPANTS: Participants were 1904
      and 1752 NH residents, 45 years or older, hospitalized in 2005 and 2006,
      respectively. MEASUREMENTS: In-hospital mortality. METHODS: A multivariable
      logistic regression model was developed to determine independent predictors of in
      hospital mortality using the 2005 dataset. The model was then applied to the 2006
      dataset to determine the generalizability of the predictors. RESULTS: Significant
      independent predictors of in-hospital mortality in 2005 included age 85 years or
      older (adjusted odds ratio [OR], 2.53; 95% confidence interval [CI], 1.21-5.30;
      P=.013), acute respiratory failure (adjusted OR, 5.67; 95% CI, 3.51-9.17; P <
      .0001), septicemia (adjusted OR, 4.63; 95% CI, 3.08-6.96; P < .0001), and acute
      renal failure (adjusted OR, 2.11; 95% CI, 1.30-3.41; P=.002). The following
      baseline characteristics also predicted in-hospital mortality in 2006: age 85
      years or older (adjusted OR, 2.45; 95% CI, 1.31-4.59; P=.005), acute respiratory
      failure (adjusted OR, 7.11; 95% CI, 4.46-11.33; P < .0001), septicemia (adjusted
      OR, 3.91; 95% CI, 2.64-5.80; P < .0001), and acute renal failure (adjusted OR,
      2.75; 95% CI, 1.82-4.15; P < .0001). Chronic morbidities were not associated with
      in-hospital mortality. CONCLUSION: Among hospitalized NH residents, age 85 years
      or older and several acute conditions, but not chronic morbidities, predicted in
      hospital mortality. Elderly NH residents at risk of developing these acute
      conditions may benefit from palliative care.

PMID- 20129216
TI  - Influenza immunization coverage among residents of long-term care facilities
      certified by CMS, 2005-2006: the newest MDs quality indicator.
AB  - BACKGROUND: In October 2005, the Centers for Medicare and Medicaid Services (CMS)
      required that long-term care (LTC) facilities certified by CMS offer each
      resident annual influenza vaccination. Subsequently, vaccination status was added
      to resident assessments collected beginning in the influenza season, 2005-2006.
      This is the first year immunization coverage can be reported based on a census of
      LTC residents. OBJECTIVES: Report influenza immunization coverage for LTC
      residents by state, resident, and facility characteristics. Identify uses of the
      data and areas in need of improvement. METHODS: Analysis of CMS' Minimum Data Set
      of 1,851,676 residents in nursing homes from October 1 through December 31 but
      who could have been discharged between January 1 and March 31 merged with data
      for 14,493 non-hospital-based facilities from the Online Survey and Certification
      Assessment Reporting System. RESULTS: Overall, 83% of residents were offered the
      vaccine and 72% had received the vaccine. Almost 10% refused to receive the
      vaccine, 14% were not offered the vaccine, 1% were ineligible, and 3% were
      missing vaccination status. Vaccination coverage varied significantly among
      states (range: 49% to 87%). Fewer African Americans and Hispanics than whites
      were offered the vaccine (79% and 79% versus 84%, respectively) and received it
      (65% and 66% versus 73%, respectively); more African Americans refused the
      vaccine (12%) than residents of other races and/or ethnicities. Residents of
      Medicaid-certified-only facilities had higher levels of vaccination than
      residents of other facilities (82% versus < or =73%). CONCLUSION: MDS
      immunization data can be used as surveillance to work with states to improve
      coverage. Further research to examine racial disparities in vaccination among LTC
      residents is needed.

PMID- 20129217
TI  - Preventing aspiration in the nursing home: the role of biofilm and data from the
      ICU.
AB  - Two aspiration syndromes have been identified: Aspiration pneumonia is infectious
      caused by micro-aspiration of oral bacteria secondary to neurogenic dysphagia or
      sedation. Infectious bacteria may also be aspirated from the stomach. Aspiration
      pneumonitis classically follows large bolus aspiration of food, acid, or
      digestive enzymes and is initially noninfectious. Large bolus gastric aspiration
      events may have an acute/dramatic onset. This article discusses (1) prevention of
      recurrent aspiration events caused by 2 common motility disorders: neurogenic
      dysphagia and gastro esophageal reflux; (2) mechanical source control
      (debridement/drainage) of sites that may harbor large collections of bacteria
      protected from antibiotics in biofilm including dental plaque, coated tongue, and
      chronic sinusitis.

PMID- 20129218
TI  - A revolution in long-term care?

PMID- 20129220
TI  - Taking leave, giving thanks.

PMID- 20129221
TI  - The use of lactational amenorrhea as a method of family planning in eastern
      Turkey and influential factors.
AB  - Although the lactational amenorrhea method (LAM) is commonly used for
      contraception, it frequently fails and pregnancy ensues. This descriptive study
      was conducted to determine the status of the use of breastfeeding as a method of
      family planning and the influential factors that may have contributed to the
      success or failure of LAM. The research sample was comprised of 188 women with 6
      month-old infants in eastern Turkey. A semistructured interview form was used for
      data collection in face-to-face meetings with the women during visits in their
      homes. In this study, 34% of the women used LAM to prevent pregnancy after
      childbirth. However, it was observed that only 17.2% of women using LAM fulfilled
      the LAM criteria with success, and 82.8% did not fulfill one or more of the LAM
      criteria. The pregnancy rate of women using this method was 32.8%. Two of the
      three basic criteria necessary for LAM to be effective were not met by the women:
      having menses (43.8%) and starting supplemental feeding (70.3%). Prenatal and
      postnatal counseling services need to be integrated and include information and
      education about the criteria that are necessary for LAM to be used effectively.
      These services should be given to women who choose to use LAM for contraception.

PMID- 20129222
TI  - Revisiting the hallmarks of midwifery.

PMID- 20129223
TI  - Toward unification of the midwifery profession: looking back to guide us now.

PMID- 20129224
TI  - Midwifery and the crowning of health care reform.

PMID- 20129225
TI  - Managing mental health conditions in primary care settings.
AB  - Depression is one of the most commonly encountered conditions in women's health,
      but many providers lack the knowledge and skills needed to identify and manage
      depression in primary care settings. This article discusses strategies that can
      improve the identification and treatment of depression. In addition, it describes
      how these strategies were incorporated into an urban inner-city health center.
      These strategies used in this setting can be adapted for use in either
      comprehensive health care centers or in practices providing primarily obstetric
      and gynecologic services.

PMID- 20129226
TI  - Measurement of blood loss: review of the literature.
AB  - It is important to recognize excessive blood loss during childbirth, which is a
      significant cause of morbidity and mortality. This article reviews methods to
      measure blood loss that could be used during childbirth. PubMed, CINAHL, and
      MEDLINE databases were searched using the phrases "blood loss" and "measurement."
      The bibliographies of publications were scanned for applicable references. A
      total of 46 publications are included in this review. The methods used to measure
      blood loss are categorized into visual estimation, direct measurement,
      gravimetric, photometry, and miscellaneous. Methods are described and compared. A
      combination of direct measurement and gravimetric methods are the most practical.
      Photometry is the most precise, but also the most expensive and complex to use. A
      variety of miscellaneous methods are presented, but none is a practical or
      reliable method. Visual estimation of blood loss is so inaccurate that its
      continued use in practice is questionable and it should not be used in research
      to evaluate treatment.

PMID- 20129227
TI  - Consultation, referral, and collaboration between midwives and obstetricians:
      lessons from New Zealand.
AB  - There has been substantial growth in the provision of midwifery-led models of
      care, yet little is known about the obstetric consultation and referral practices
      of these midwives or the quality of the collaboration between midwives and
      obstetricians. This study aimed to describe these processes as they are practised
      in New Zealand, where midwifery-led maternity care is the dominant model. A total
      population postal survey was conducted that included 649 New Zealand midwives who
      provided midwifery-led care in 2001. There was a 56.5% response rate, describing
      care for 4251 women. Within this cohort, there was a 35% consultation rate and
      43% of these women had their lead carer role transferred to an obstetrician.
      However, the midwives continued to provide care in collaboration with
      obstetricians for 74% of transferred women. Seventy-two percent of midwives felt
      that they were well supported by the obstetricians to continue care. Midwifery
      led care is reasonable for the general population of childbearing women, and a
      35% consultation rate can be seen as a benchmark for this population. Midwives
      can, when well supported, provide continuity of care for women who experience
      complexity during pregnancy and/or birth. Collaboration with obstetricians is
      possible, but there needs to be further work to describe what successful
      collaboration is and how it might be fostered.

PMID- 20129228
TI  - How caregivers manage pain and distress in second-stage labor.
AB  - Innovative care interactions are needed when helping a woman who exhibits severe
      pain or distress during the second stage of labor. We describe how caregivers and
      laboring women interacted during second-stage labor, with particular attention to
      how caregivers managed pain and distress. We used observational methods to
      perform a microanalysis of behaviors from video-recorded data. Pain occurred
      during labor contractions, and distress (an emotional response to pain)
      manifested primarily between contractions. Four patterns of women's behavior were
      identified: 1) no pain or distress, 2) low-level pain and/or distress, 3) focused
      working, and 4) severe pain and/or distress. Successful care was identified as
      enabling the woman to maintain herself in any state other than severe pain and/or
      distress. Particular modes of speech used by the caregiver enabled the attainment
      of successful care when the woman was not in severe pain or distress. When severe
      pain or distress existed, innovative caregiving transitioned the woman to another
      state. Successful intervention strategies included 1) giving innovative
      directions and 2) "talking down." Ordinary modes of "birth talk" can be used when
      severe pain or distress is not manifested and when the primary care problem is to
      assist women with bearing down. Innovative care interactions are needed when
      faced with severe pain or distress. Managing labor pain is an ongoing focus of
      clinicians who provide care to women in labor. In addition to pain, women might
      also experience distress, an emotional response to the labor experience. Whether
      from choice or necessity, caregivers for laboring women need nonpharmacologic
      interventions and interpersonal skills that can help women endure labor and give
      birth. Labor is hard work, and even in precipitous labors most women require
      assistance. Care given to a laboring woman consists of employing comforting
      strategies that help her cope with the pain of uterine contractions. The purpose
      of these comfort strategies is to help the woman find needed resilience during
      labor. Most cultures have mechanisms for providing this kind of support. In this
      article, we identify patterns of behavior used by laboring women and describe
      successful and unsuccessful strategies used by caregivers to help these women
      deal with pain and distress during the second stage of labor.

PMID- 20129229
TI  - Knowledge of female genital cutting and experience with women who are
      circumcised: a survey of nurse-midwives in the United States.
AB  - Thousands of women with a history of female genital cutting (FGC) have immigrated
      to the United States. The purpose of this study was to assess certified nurse
      midwives' (CNMs') knowledge of FGC and to explore their experiences caring for
      African immigrant women with a history of genital cutting. A descriptive survey
      design was used. A random sample of 600 CNMs from the member list of the American
      College of Nurse-Midwives was surveyed. Two hundred forty-three CNMs completed a
      survey of FGC knowledge and provider experience. The respondents exhibited more
      correct medical knowledge about FGC than knowledge of cultural and legal issues.
      Differences in correct or incorrect knowledge were statistically significant
      based on provider experience. Almost 70% of respondents could identify
      infibulation. Less than 20% knew that both Muslim and Christian women are
      circumcised. Fifty-seven percent knew that it is illegal in the United States to
      circumcise women younger than 18 years of age. We found that discussions between
      CNMs and clients who were circumcised regarding FGC-related concerns and
      complications were minimal. Women with a history of FGC want female providers.
      Reinfibulation poses an ethical dilemma for some CNMs. Nurse-midwives in the
      United States need to learn more about FGC and the cultures of their clients in
      order to provide culturally competent care.

PMID- 20129230
TI  - Perceptions and practice of waterbirth: a survey of Georgia midwives.
AB  - This study investigated the experience and perceptions of Georgia certified nurse
      midwives about waterbirth and their level of support for establishing waterbirth
      in their work setting. A survey was distributed to a convenience sample of 119
      certified nurse-midwives from the American College of Nurse Midwives, Georgia
      chapter; 45% of those surveyed responded. The majority of midwives had some
      exposure to waterbirth through self-education or through clinical practice. More
      than half supported the incorporation of waterbirth in their workplace setting.
      Maternal relaxation and reduced use of analgesia were perceived as the greatest
      benefit of waterbirth. Of 11 items related to disadvantages of waterbirth,
      certified nurse-midwives were moderately to severely concerned about none. The
      most concerning factors, with a mean of 2.4 to 2.5 on a scale of 1 (no worry) to
      5 (severe worry), were maintenance of water temperature, physical stress on the
      midwife, and inability to see the perineum. Midwives' support for waterbirth
      focused mostly on the perceived benefits to the mother with little worry about
      the risks.

PMID- 20129231
TI  - A community intervention on portion control aimed at weight loss in low-income
      Mexican American women.
AB  - A pilot study was conducted to determine if a nutritional intervention aimed at
      portion control leads to significant weight loss in a community of low-income
      Mexican American women. Nineteen low-income Mexican American women were
      randomized to a standard care group or an intervention group in portion control.
      The trial was 20 weeks in length, and the intervention included four 2-hour
      classes. Both interventions were administered by a certified nurse-midwife (CNM)
      and a promotora de salud (i.e., lay health advisor). Women in the intervention
      group lost more weight than women in the standard care group, though this
      difference was not statistically significant. The mean weight loss in the
      intervention group was 6.57 pounds (2.9 kg) compared to a mean weight loss of 2.8
      pounds (1.3 kg) in the standard care group (P = .47). Mean weight loss,
      regardless of group, was significantly greater when participants reported self
      weighing (P = .02). This pilot study in portion control for low-income Mexican
      American women merits further study.

PMID- 20129232
TI  - Management of protracted active labor with nipple stimulation: a viable tool for
      midwives?

PMID- 20129233
TI  - So many materials, so little time: a checklist to select printed patient
      education materials for clinical practice.

PMID- 20129234
TI  - Client impact on a clinician doing research.

PMID- 20129238
TI  - Building bridges.

PMID- 20129239
TI  - Role of single photon emission computed tomography in the diagnosis of chronic
      low back pain.

PMID- 20129240
TI  - So why does my back hurt doc?

PMID- 20129241
TI  - HELP for AML: methylation profiling opens new avenues.
AB  - There is growing evidence that aberrant gene expression in cancer is linked to
      epigenetic deregulation like promoter cytosine methylation in CpG-islands. In
      this issue of Cancer Cell, Figueroa et al. show that genome-wide promoter DNA
      methylation profiling reveals unique AML subgroups and methylation patterns that
      are associated with clinical outcome.

PMID- 20129242
TI  - All you need is a Mir-acle: the role of nontranslated RNAs in the suppression of
      B cell chronic lymphocytic leukemia.
AB  - miR-15a and miR-16-1 were the first microRNAs linked to cancer because their
      genes are commonly deleted in human chronic lymphocytic leukemia (CLL). In this
      issue of Cancer Cell, Klein and coworkers show that deleting a region with these
      genes in mouse provides a faithful model for human CLL.

PMID- 20129243
TI  - A tumor suppressor SIRTainty.
AB  - Sirtuin deacetylases are linked to longevity, aging, and stress responses. In
      this issue of Cancer Cell, Kim et al. show that SIRT3 functions as a tumor
      suppressor by enhancing the expression of mitochondrial MnSOD. Loss of SIRT3
      leads to increased mitochondrial ROS, which then enhances cellular transformation
      and tumor growth.

PMID- 20129244
TI  - IDH1 mutations in gliomas: when an enzyme loses its grip.
AB  - The growing interest in cancer metabolism is best demonstrated by the rapid
      progress made in studying isocitrate dehydrogenase (IDH) mutations since their
      discovery just over a year ago. In a recent study published in Nature, Dang et
      al. identified 2-hydroxyglutarate as a product of tumor-associated IDH mutants
      with potential oncogenic activities.

PMID- 20129245
TI  - SUMO boosts the DNA damage response barrier against cancer.
AB  - Cells exposed to genotoxic insults such as ionizing radiation activate a
      signaling cascade to repair the damaged DNA. Two recent articles published in
      Nature show that such genome maintenance requires modifications of tumor
      suppressor proteins BRCA1 and 53BP1 by the small ubiquitin-like modifier SUMO.

PMID- 20129246
TI  - SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of
      mitochondrial integrity and metabolism during stress.
AB  - The sirtuin gene family (SIRT) is hypothesized to regulate the aging process and
      play a role in cellular repair. This work demonstrates that SIRT3(-/-) mouse
      embryonic fibroblasts (MEFs) exhibit abnormal mitochondrial physiology as well as
      increases in stress-induced superoxide levels and genomic instability. Expression
      of a single oncogene (Myc or Ras) in SIRT3(-/-) MEFs results in in vitro
      transformation and altered intracellular metabolism. Superoxide dismutase
      prevents transformation by a single oncogene in SIRT3(-/-) MEFs and reverses the
      tumor-permissive phenotype as well as stress-induced genomic instability. In
      addition, SIRT3(-/-) mice develop ER/PR-positive mammary tumors. Finally, human
      breast and other human cancer specimens exhibit reduced SIRT3 levels. These
      results identify SIRT3 as a genomically expressed, mitochondria-localized tumor
      suppressor.

PMID- 20129247
TI  - IAP regulation of metastasis.
AB  - Inhibitor-of-Apoptosis (IAP) proteins contribute to tumor progression, but the
      requirements of this pathway are not understood. Here, we show that
      intermolecular cooperation between XIAP and survivin stimulates tumor cell
      invasion and promotes metastasis. This pathway is independent of IAP inhibition
      of cell death. Instead, a survivin-XIAP complex activates NF-kappaB, which in
      turn leads to increased fibronectin gene expression, signaling by beta1
      integrins, and activation of cell motility kinases FAK and Src. Therefore, IAPs
      are direct metastasis genes, and their antagonists could provide antimetastatic
      therapies in patients with cancer.

PMID- 20129248
TI  - Cyclin D1 kinase activity is required for the self-renewal of mammary stem and
      progenitor cells that are targets of MMTV-ErbB2 tumorigenesis.
AB  - Transplantation studies have demonstrated the existence of mammary progenitor
      cells with the ability to self-renew and regenerate a functional mammary gland.
      Although these progenitors are the likely targets for oncogenic transformation,
      correlating progenitor populations with certain oncogenic stimuli has been
      difficult. Cyclin D1 is required for lobuloalveolar development during pregnancy
      and lactation as well as MMTV-ErbB2- but not MMTV-Wnt1-mediated tumorigenesis.
      Using a kinase-deficient cyclin D1 mouse, we identified two functional mammary
      progenitor cell populations, one of which is the target of MMTV-ErbB2. Moreover,
      cyclin D1 activity is required for the self-renewal and differentiation of
      mammary progenitors because its abrogation leads to a failure to maintain the
      mammary epithelial regenerative potential and also results in defects in luminal
      lineage differentiation.

PMID- 20129249
TI  - Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC.
AB  - MET amplification activates ERBB3/PI3K/AKT signaling in EGFR mutant lung cancers
      and causes resistance to EGFR kinase inhibitors. We demonstrate that MET
      activation by its ligand, HGF, also induces drug resistance, but through GAB1
      signaling. Using high-throughput FISH analyses in both cell lines and in patients
      with lung cancer, we identify subpopulations of cells with MET amplification
      prior to drug exposure. Surprisingly, HGF accelerates the development of MET
      amplification both in vitro and in vivo. EGFR kinase inhibitor resistance, due to
      either MET amplification or autocrine HGF production, was cured in vivo by
      combined EGFR and MET inhibition. These findings highlight the potential to
      prospectively identify treatment naive, patients with EGFR-mutant lung cancer who
      will benefit from initial combination therapy.

PMID- 20129250
TI  - Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1
      dependent inflammation.
AB  - Chronic exposure to tobacco smoke, which contains over 60 tumor-initiating
      carcinogens, is the major risk factor for development of lung cancer, accounting
      for a large portion of cancer-related deaths worldwide. It is well established
      that tobacco smoke is a tumor initiator, but we asked whether it also acts as a
      tumor promoter once malignant initiation, such as caused by K-ras activation, has
      taken place. Here we demonstrate that repetitive exposure to tobacco smoke
      promotes tumor development both in carcinogen-treated mice and in transgenic mice
      undergoing sporadic K-ras activation in lung epithelial cells. Tumor promotion is
      due to induction of inflammation that results in enhanced pneumocyte
      proliferation and is abrogated by IKKbeta ablation in myeloid cells or
      inactivation of JNK1.

PMID- 20129251
TI  - Integrated genomic analysis identifies clinically relevant subtypes of
      glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.
AB  - The Cancer Genome Atlas Network recently cataloged recurrent genomic
      abnormalities in glioblastoma multiforme (GBM). We describe a robust gene
      expression-based molecular classification of GBM into Proneural, Neural,
      Classical, and Mesenchymal subtypes and integrate multidimensional genomic data
      to establish patterns of somatic mutations and DNA copy number. Aberrations and
      gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical,
      Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal
      brain cell types show a strong relationship between subtypes and different neural
      lineages. Additionally, response to aggressive therapy differs by subtype, with
      the greatest benefit in the Classical subtype and no benefit in the Proneural
      subtype. We provide a framework that unifies transcriptomic and genomic
      dimensions for GBM molecular stratification with important implications for
      future studies.

PMID- 20129252
TI  - Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as
      adjuvant treatment for uterine papillary serous carcinoma and clear cell
      carcinoma: the Indiana University experience.
AB  - PURPOSE: To evaluate the outcomes of surgically staged patients with Stage I-IIIA
      uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC) of the
      uterus treated at Indiana University with intraperitoneal (32)P and vaginal
      brachytherapy. METHODS: Between 1997 and 2004, a total of 28 patients with Stage
      I-IIIA UPSC and CCC were treated with a standardized adjuvant therapy. All
      patients underwent comprehensive surgical staging with negative pelvic and para
      aortic lymph nodes and no gross residual disease. After a Technetium-99m
      distribution study, (32)P was administered intraperitoneally. Subsequently, high
      dose rate (HDR) vaginal cuff brachytherapy was delivered to a total dose of 2100
      cGy in three fractions prescribed to 0.5 cm depth. The records of these 28
      patients were reviewed, including 18 patients who were treated on Hoosier
      Oncology Group 97-01 (Phase II trial), and whose followup was updated. RESULTS:
      Intraperitoneal (32)P was administered at a median of 4 weeks from surgery,
      followed by vaginal brachytherapy. One patient had no available followup
      information and is not included in the analysis. The median followup for the 27
      evaluable patients was 40.9 months. No patients had Grade 2, 3, or 4
      complications related to their adjuvant treatment. There were 4 patients with
      recurrent disease: 2 initially relapsed intraperitoneally, 1 in the distal
      vagina, and 1 had a scar recurrence. Three patients have died of the disease. For
      all 27 patients, the 3-year overall survival, cause-specific survival, and
      disease-free survival were 84.2%, 90.7%, and 74.4%, respectively. CONCLUSIONS:
      Adjuvant therapy for UPSC and CCC with intraperitoneal (32)P and vaginal
      brachytherapy after adequate surgical staging and maximal cytoreduction is well
      tolerated and appears to be effective. Further study is warranted.

PMID- 20129253
TI  - Review of osteoporosis pharmacotherapy for geriatric patients.
AB  - BACKGROUND: Fractures are a significant problem in geriatric patients, and
      understanding the evidence for benefit and possible harm of osteoporosis
      treatments is critical to appropriate management of this patient population.
      OBJECTIVE: The purpose of this article was to review the evidence and treatment
      considerations related to use of the approved osteoporosis treatments in the
      United States across the continuum of ages in the geriatric population. METHODS:
      MEDLINE and the Web of Science were searched to find English-language articles
      published from 2000 through July 2009. Search terms included: practice guideline,
      osteoporosis, calcium, vitamin D, pharmacoeconomics, ethnicity, and treatment.
      The generic names of each of the osteoporosis treatments approved in the United
      States were searched to find relevant clinical trials and randomized controlled
      trials (RCTs). Pivotal trials that included fracture data or focused specifically
      on elderly patients (> or = 60 years of age) were selected. Bibliographies in the
      identified articles were searched for additional articles, and the prescribing
      information for each of the approved treatments was reviewed. RESULTS: Many
      osteoporosis studies have a mean patient age >60 years, but data for older
      patients are limited. Subanalyses of older patient groups have found risedronate
      to be beneficial for vertebral fractures in patients aged 70 to 79 years
      (absolute risk reduction [ARR], 8.4%; P < 0.001) and teriparatide to be
      beneficial for both vertebral (ARR, 6.4%; P < 0.05) and new nonvertebral
      fragility fractures (ARR, 9.9%; P < 0.05) in women aged > or = 75 years. However,
      no RCTs of geriatric patients who were either nonambulatory or had multiple
      comorbidities were identified in the literature. CONCLUSIONS: Evidence indicates
      that the osteoporosis treatments currently available in the United States are
      beneficial for treating osteoporosis in geriatric patients. However, data are
      limited for the oldest patients (> or = 80 years) and those with significant
      comorbidities. Because of the limited availability of data for geriatric patients
      with significant comorbidities, the properties of the various agents, including
      efficacy, tolerability, and potential contraindications, should be considered
      carefully for each geriatric patient.

PMID- 20129254
TI  - Pharmacologic management of the older patient with type 2 diabetes mellitus.
AB  - BACKGROUND: Pharmacologic options for the treatment of elderly patients with type
      2 diabetes mellitus (T2DM) are the same as in younger adults; however, treatment
      considerations differ in the elderly due to changes in renal and hepatic
      function, life expectancy, and various other clinical and practical
      considerations. OBJECTIVE: This article discusses geriatric considerations in the
      pharmacologic management of T2DM and reviews the potential clinical advantages
      and disadvantages of pharmacologic agents currently available for the treatment
      of T2DM, including oral and injectable medications. METHODS: A search of MEDLINE
      was conducted for articles published in English between January 1966 and
      September 2009 using the terms type 2 diabetes mellitus, elderly, geriatric,
      treatment, insulin, metformin, sulfonylurea, thiazolidinedione, alpha-glucosidase
      inhibitor, meglitinide, DPP-4 inhibitor, colesevelam, exenatide, and pramlintide.
      Meta-analyses, randomized controlled trials of pharmacologic treatment, and
      evidence-based reviews and/or expert opinions regarding the treatment of T2DM in
      the elderly were selected for review. RESULTS: In overweight patients, metformin
      has been associated with reductions in risk for all-cause mortality and stroke
      compared with insulin and sulfonylureas. Older patients who are frail, anorexic,
      or underweight and those with congestive heart failure (CHF), renal or hepatic
      insufficiency, or dehydration may not be appropriate candidates for metformin
      therapy. The substantial risk of hypoglycemia with insulin secretagogues is
      increased by 36% in the elderly compared with younger adults; however, this risk
      is counterbalanced by the extensive clinical experience with these agents in the
      geriatric population. Thiazolidinediones should generally be avoided in patients
      with CHF and are absolutely contraindicated in patients with class II-IV heart
      failure. They have been associated with peripheral edema, as well as with
      decreases in bone mineral density in women. There is limited information on the
      use of dipeptidyl peptidase-4 inhibitors in the elderly, although dose adjustment
      is required in patients with renal compromise. In practice, substantial
      gastrointestinal adverse effects limit the use of alpha-glucosidase inhibitors in
      older patients. Colesevelam is associated with numerous drug interactions and can
      cause new or worsening constipation. There are limited data on the use of
      exenatide in the elderly. It may be beneficial in older patients with limited
      mobility who could benefit from weight loss, whereas it may not be a good option
      for frail, underweight adults. Use of exenatide is not recommended in patients
      with a creatinine clearance <30 mL/min. Given the increased monitoring required
      to avoid hypoglycemic events with pramlintide, this agent should be used with
      caution in older adults, particularly the frail elderly. Most patients with T2DM
      eventually require insulin; however, due to the risk of hypoglycemia and related
      morbidity, careful use of insulin is warranted in the geriatric population.
      CONCLUSIONS: Overall, there is a scarcity of data regarding the use of
      pharmacologic agents in older adults with T2DM, and clinical guidance is largely
      based on data obtained from younger populations. The selection of appropriate
      drug regimens for these patients remains challenging.

PMID- 20129255
TI  - Outcomes of irinotecan-based chemotherapy regimens in elderly Medicare patients
      with metastatic colorectal cancer.
AB  - BACKGROUND: Several population-based studies have confirmed the benefits of
      adjuvant chemotherapy with 5-fluorouracil/leucovorin for treatment of colorectal
      cancer. Few population-based studies have evaluated other chemotherapies that are
      now available for colorectal cancer management. OBJECTIVE: This study primarily
      sought to evaluate the survival benefit of first-line irinotecan use in a group
      of Medicare patients with stage IV (metastatic) colorectal cancer. METHODS: Data
      on chemotherapy users with a diagnosis of colorectal cancer reported between 1998
      and 2002 were obtained from the Surveillance Epidemiology and End Results (SEER)
      Medicare database. Irinotecan, marketed in 1997, was one of the newer
      chemotherapy agents in the available data. Chemotherapy episodes, defined as
      periods of continuous chemotherapy treatment with no gaps >90 days between
      successive claims, were identified. The first chemotherapy episode after
      diagnosis was used to identify lines of treatment: patients may have initiated
      irinotecan therapy within 2 months (first-line), used irinotecan later in the
      first episode (second-line), or not used irinotecan at all. Descriptive
      statistics were generated and a multivariable Cox proportional hazards model was
      used to determine the survival benefit of irinotecan. Secondary analyses explored
      the survival benefit in specific patient subgroups. The impact of irinotecan use
      on health care utilization also was assessed. RESULTS: Of 3327 chemotherapy users
      (mean/median age, 75 years), 842 (25.3%) initiated chemotherapy using irinotecan.
      No overall survival benefit for irinotecan was observed in the primary analysis
      comparing irinotecan initiators with all other chemotherapy users (including
      those who used irinotecan subsequently). Covariates that were negatively
      associated with survival included older age, presence of >1 comorbidity, a high
      tumor grade, lymph node involvement, and a primary tumor site in the colon.
      Surgery was positively associated with a lower hazard of death. In subgroup
      analyses that excluded subsequent irinotecan users, a survival benefit for
      irinotecan was observed but diminished over time. Irinotecan users had higher
      rates of hospitalizations possibly due to chemotherapy-related adverse effects.
      This retrospective claims study had limitations such as a lack of information on
      patient performance status, dosing, and the types of regimens used; hence,
      certain assumptions had to be made and selection bias may have been involved.
      CONCLUSIONS: The definitive survival advantage of irinotecan observed in clinical
      trials was not reproducible in this population of elderly Medicare patients. The
      results emphasize the need for expansion of trials to include a more diverse
      patient group as well as continued evaluation of more recent chemotherapies in
      real-world settings.

PMID- 20129256
TI  - National utilization of transdermal fentanyl among community-dwelling older
      people in Finland.
AB  - BACKGROUND: The use of opioids has increased rapidly in Europe and North America,
      and older people may be susceptible to opioid-related adverse drug events. The
      Finnish National Agency for Medicines has recommended that oral opioids be
      considered the first-line treatment when a strong opioid is required for severe
      pain. OBJECTIVE: The objective of this study was to investigate and describe the
      age-, indication-, sex-, and geographic-specific utilization of transdermal
      fentanyl among older people residing in noninstitutional settings in Finland.
      METHODS: Reimbursement data for fentanyl, morphine, oxycodone, and hydromorphone
      were extracted from the Finnish National Prescription Register for 2008. Age
      specific population data were used to calculate the annual prevalence of opioid
      use for malignant and nonmalignant pain for patients aged < or = 64, 65 to 69, 70
      to 74, 75 to 79, 80 to 84, 85 to 89, 90 to 94, 95 to 99, and >99 years. The
      annual prevalence of transdermal fentanyl use was also calculated separately for
      each of the 21 hospital districts in Finland. RESULTS: Reimbursement for
      transdermal fentanyl was paid to 2746 people for malignant pain and 6223 people
      for nonmalignant pain. The annual prevalence of transdermal fentanyl use for
      nonmalignant pain was lowest among men aged < or = 64 years (2.2 users/10,000
      men) and highest among women >99 years (539.2 users/10,000 women). The annual
      prevalence of transdermal fentanyl use was >47 times higher than that of morphine
      for nonmalignant pain among people aged 85 to 89 years and >97 times higher than
      that of morphine among people aged 90 to 94 years. A greater than 4-fold
      variation in the annual prevalence of transdermal fentanyl use was reported among
      the 21 hospital districts in Finland (range, 9.5-40.6/10,000 inhabitants).
      CONCLUSIONS: The prevalence of transdermal fentanyl use was higher than that of
      morphine, oxycodone, and hydromorphone among people aged > or = 80 years residing
      in noninstitutional settings in Finland. The variation in use between hospital
      districts suggests that organizational culture may have a strong impact on
      prescribing practices. Our data highlight the need for further education
      regarding the appropriate use of opioids among older people.

PMID- 20129257
TI  - Methodology of a pilot study to improve the quality of medication use in older
      adults: Enhancing Quality in Psychiatry Using Pharmacists (EQUIPP).
AB  - BACKGROUND: Medication-related problems are prevalent in older adults,
      contributing to increased harm and health care costs and negatively impacting
      quality of care. Older adults with psychiatric disease are at an increased risk
      because of their underlying disease and types of medications prescribed. Efforts
      to improve the quality of medication use often focus on select medication-related
      problems, select diagnoses, or predefined quality indicators; however, such an
      approach fails to consider the potential for multiple coexisting problems within
      individuals. OBJECTIVE: A pilot study was conducted to test the feasibility of a
      medication management program designed to improve the quality of medication use
      in older adults with underlying psychiatric disease. This article describes the
      methodology of the study and details of the intervention, and presents baseline
      characteristics of the study population. METHODS: English-speaking psychiatry
      outpatients aged > or = 65 years taking > or = 2 drugs that are active in the
      central nervous system were enrolled into a medication management program, in
      which medication management was provided by a clinical pharmacist for 6 months.
      Patients were evaluated at baseline, 3 months, and 6 months. Data were collected
      on the patients' demographic characteristics, health and medications, health
      literacy, functional status, symptoms of depression, health services utilization,
      quality of medication use, adherence, and patient satisfaction with the program.
      RESULTS: One hundred seventy-three older adults were assessed for inclusion; 146
      were not eligible, not reachable, or not interested in participating. Twenty
      seven older adults were enrolled in the study, all but one of whom completed the
      3- and 6-month visits. The mean (SD) age of the 27 participants was 74.7 (8.1)
      years; 63% were female, 74% were white, and 70% had no cognitive impairment.
      CONCLUSIONS: This pilot study tested the feasibility of a medication management
      program designed to improve the quality of medication use in older adults with
      underlying psychiatric disease. Findings from this study, which will be reported
      at a later date, will help to refine the program and subsequent testing, with the
      overall goal of improving the quality of medication use and health outcomes in
      older adults.

PMID- 20129258
TI  - Impact of solifenacin on quality of life, medical care use, work productivity,
      and health utility in the elderly: an exploratory subgroup analysis.
AB  - BACKGROUND: Overactive bladder (OAB) is a common problem among the elderly and a
      financial burden to society. The prevalence of OAB increases with age and affects
      > or = 25% of people aged > or = 65 years. OBJECTIVE: The goal of this
      exploratory subgroup analysis of the VESIcare Efficacy and Research Study US
      (VERSUS) was to assess changes in health-related quality of life (HRQoL), medical
      care resource utilization, work and activity impairment, and health utility among
      elderly patients with OAB who continued to have urgency symptoms with tolterodine
      and were willing to try solifenacin. METHODS: This was a 12-week, multicenter,
      prospective, open-label, noncomparative, flexible-dosing study designed to assess
      the efficacy and tolerability of solifenacin. Patients who received tolterodine 4
      mg/d for > or = 4 weeks but continued to experience urgency symptoms (> or = 3
      urgency episodes/24 hours) were enrolled. This exploratory analysis describes
      results from 2 elderly cohorts (patients 65 to 74 years and > or = 75 years of
      age). After a washout period of > or = 14 days, patients began treatment with
      solifenacin 5 mg/d with dosing adjustments allowed at week 4 (to 10 mg/d) and at
      week 8 (back to 5 mg/d for patients whose dose was increased to 10 mg/d at week
      4). Outcomes were assessed using the OAB-q (a questionnaire specific to OAB and
      HRQoL), the Work Productivity and Activity Impairment-Specific Health Problem
      index, the Medical Care Use Index, and the Health Utilities Index Mark 2 and Mark
      3 (HUI2/3), administered at the prewashout and week-12 visits. RESULTS: The
      subgroup analysis included 108 patients 65 to 74 years of age and 86 patients >
      or = 75 years of age. Patients in both age groups experienced significant
      improvement in HRQoL (P < 0.001), as well as significant reductions in
      nonprotocol-related office visits (P < 0.001) and activity impairment (P <
      0.025). A significant reduction in the use of pads/diapers was reported for
      patients 65 to 74 years of age (P < 0.018), and patients in this age group who
      were working reported significantly less impairment related to OAB while working
      during solifenacin treatment than during tolterodine treatment (P < 0.042). No
      significant differences in HUI2/3 scores were observed in either of the elderly
      subgroups. CONCLUSIONS: Overall, solifenacin was found to improve symptom bother,
      HRQoL, work productivity, activity participation, and reduced medical care
      resource utilization in these elderly subjects with OAB who continued to have
      urgency symptoms with tolterodine and were willing to try solifenacin. This was
      an exploratory subgroup analysis of an open-label, noncomparative study; further
      research is needed to confirm these results.

PMID- 20129259
TI  - Self-reported use of natural health products: a cross-sectional telephone survey
      in older Ontarians.
AB  - BACKGROUND: The self-reported use of natural health products (NHPs) (herbal
      products and vitamin and mineral supplements) has increased over the past decade
      in Canada. Because the elderly population might have comorbidities and
      concurrently administered medications, there is a need to explore the perceptions
      and behaviors associated with NHPs in this age group. OBJECTIVE: The goal of this
      study was to assess the use of NHPs in a cohort of older Canadian residents and
      the characteristics, perceptions, and behaviors associated with NHP use. METHODS:
      Survey participants aged > or = 60 years were randomly selected from telephone
      listings in the area of greater Hamilton, Ontario, Canada. Data were collected
      using a standardized computer-assisted telephone interview system. Self-reported
      data covering 7 domains were collected: (1) demographics; (2) self-reported 12
      month NHP use; (3) reasons for NHP use; (4) self-reported 12-month prescription
      medication use; (5) expenditures on NHPs; (6) patient-reported adverse events and
      drug-NHP interactions; and (7) perceptions of physicians' attitudes regarding
      NHPs. Descriptive statistics were used to compare the characteristics of NHP
      users with those of nonusers and to assess the characteristics of NHP users
      across these 7 domains. Multivariate regression analysis was conducted to
      determine the demographic variables that might be associated with NHP user
      status. RESULTS: Of 2528 persons identified as age > or = 60 years, 1206 (48%)
      completed the telephone interview. Six hundred sixteen of these respondents (51%)
      reported the use of > or = 1 NHP during the previous 12 months. On the initial
      univariate analysis, younger age and higher income were significantly associated
      with reporting NHP use (mean age, users vs nonusers, 71.1 vs 72.7 years,
      respectively; 95% CI, 1.02-1.06; P < 0.001; income more than Can $26,000 was 28%
      and 22% in users and nonusers, respectively; P = 0.028). One hundred seventy of
      616 users (28%) used an NHP to treat the same condition for which they were
      concurrently receiving a prescription medication, and 43 (25%) had not informed
      their physicians about their NHP use. Patients' characteristics such as sex,
      education, smoking status, and self-reported health status did not differ
      significantly between users and nonusers. In individuals who regularly spent
      money to purchase NHPs (n = 394), the mean cost was $20.38/mo. NHP expenditure
      was not significantly associated with age, sex, or income. CONCLUSION: Based on
      these findings, a substantial proportion of those Ontarians aged > or = 60 years
      reported NHP use, and there is a need for greater communication with physicians
      to avoid potential drug-NHP interactions.

PMID- 20129260
TI  - US Preventive Services Task Force recommendations for screening mammography:
      evidence-based medicine or the death of science?

PMID- 20129261
TI  - Farewell ... and welcome.

PMID- 20129262
TI  - Sipping muddy water.

PMID- 20129263
TI  - Standing our ground.

PMID- 20129264
TI  - New codes from a new source: the rolling five-year review.

PMID- 20129265
TI  - Bullshit.

PMID- 20129266
TI  - Leading change in an organization.
AB  - Change leadership is a core function of your leadership role. Learning to do it
      better will help you in many of the other tasks you face in your position. Change
      and adapting to it are not optional; change is simply a fact in the environment.
      Ignoring it in your job is no less critical than trying to ignore an oncoming
      truck in the wrong lane. Change leadership will be easier for you and your
      organization if it is embedded in policies and smart practices rather than done
      in an ad hoc fashion.

PMID- 20129267
TI  - Breast cancer screening with imaging: recommendations from the Society of Breast
      Imaging and the ACR on the use of mammography, breast MRI, breast ultrasound, and
      other technologies for the detection of clinically occult breast cancer.
AB  - Screening for breast cancer with mammography has been shown to decrease mortality
      from breast cancer, and mammography is the mainstay of screening for clinically
      occult disease. Mammography, however, has well-recognized limitations, and
      recently, other imaging including ultrasound and magnetic resonance imaging have
      been used as adjunctive screening tools, mainly for women who may be at increased
      risk for the development of breast cancer. The Society of Breast Imaging and the
      Breast Imaging Commission of the ACR are issuing these recommendations to provide
      guidance to patients and clinicians on the use of imaging to screen for breast
      cancer. Wherever possible, the recommendations are based on available evidence.
      Where evidence is lacking, the recommendations are based on consensus opinions of
      the fellows and executive committee of the Society of Breast Imaging and the
      members of the Breast Imaging Commission of the ACR.

PMID- 20129268
TI  - Radiology resource utilization during an H1N1 influenza outbreak.
AB  - PURPOSE: This study was conducted to evaluate the radiology resources utilized by
      patients infected with novel influenza A (H1N1) during the 2009 summer outbreak
      to aid in pandemic planning for the 2010 influenza season. MATERIALS AND METHODS:
      Of the 222 patients diagnosed or presumed to have H1N1 infection in the authors'
      health system from May 1 to July 18, 2009, 66 received imaging, including at
      least one chest imaging study directly related to the infection. Fourteen of
      these patients required advanced mechanical ventilation and were admitted to the
      intensive care unit (ICU; group 1); the remainder were managed as outpatients (27
      of 52) or required brief hospitalizations (25 of 52) without mechanical
      ventilation (group 2; n = 52). The imaging histories of all 66 patients were
      reviewed for the period of hospitalization for group 1 patients and from 10 days
      before to 30 days after the diagnosis of influenza infection for group 2 patients
      to determine the number, types, and temporal distribution of radiology procedures
      performed during the flu outbreak. RESULTS: Thirty percent of all patients with
      known or presumed influenza (H1N1) underwent radiologic imaging. The 14 patients
      in the ICU received a total of 469 chest radiographic studies (mean, 33.5), 15
      thoracic CT examinations, and 170 additional imaging studies, the most common of
      which were 72 abdominal radiographic studies and 16 abdominal CT examinations.
      Seventy-one percent (334 of 469) of all the radiographic examinations in ICU
      patients were obtained during a single month. In contrast, group 2 patients
      received a total of 71 chest radiographic studies (mean, 1.4), 6 thoracic CT
      examinations, and 28 additional imaging studies, spread roughly evenly over the
      study period, with a subtle peak in early June. CONCLUSIONS: The majority of
      patients with H1N1 infection (70%) received no imaging studies. Patients
      sufficiently ill to require some level of imaging had, on average, just over one
      chest radiographic study. The 6% of patients who required ICU stays received an
      average of 33.5 chest radiographic studies and one thoracic CT examination. This
      information should be useful for health care organizations in planning their
      radiology resource needs during an H1N1 flu pandemic.

PMID- 20129269
TI  - A prior authorization program of a radiology benefits management company and how
      it has affected utilization of advanced diagnostic imaging.
AB  - Radiology benefits management companies have evolved in recent years to meet the
      need to control the rapid growth in advanced diagnostic imaging. The Obama
      administration and other key policymakers have proposed using them as a cost
      control mechanism, but little is known about how they operate or what results
      they have produced. The main tool they use is prior authorization. The authors
      describe the inner workings of the call center of one radiology benefits
      management company and how its prior authorization program seems to have slowed
      the growth in the utilization of MRI, CT, and PET in the large markets of one
      commercial payer.

PMID- 20129270
TI  - "Hyperscrutiny" of academic-industrial relationships: potential for unintended
      consequences--a response.
AB  - In the current environment, academic-industrial relationships are coming under
      intense scrutiny from government and other regulatory bodies. Although there
      clearly have been incidents of abuse in these relationships, academic-industrial
      collaboration is an engine that drives innovation in the biomedical sciences in
      this country. The academic radiology community must ensure that the societal
      benefits of these relationships are not sacrificed via "overregulation."

PMID- 20129271
TI  - Bundled payments: bundled risk or bundled reward?
AB  - One potential option of President Obama's proposed health care plan is to change
      from fee-for-service to episode-of-care payments. These global payments would
      combine physician and hospital reimbursement from admission to discharge. In an
      effort to further evaluate this strategy, CMS has initiated a pilot study called
      the Acute Care Episode (ACE) Demonstration. Five hospitals in the United States
      have been chosen to participate. The authors review the history of bundled
      payments, the current ACE Demonstration, and the opinions of those radiologists
      involved and attempt to outline a plan for hospital-based practices to prepare
      for this possible scenario.

PMID- 20129272
TI  - Role models in academic radiology: current status and pathways to improvement.
AB  - PURPOSE: The aim of this study was to determine residents' attitudes about the
      influence and characteristics of academic radiology role models. METHOD: A Web
      based survey was sent to the 35 residents in the 2007 Siemens AUR Radiology
      Resident Academic Development (SARRAD) program and to all other residents at
      their institutions. The survey contained questions regarding experiences with and
      desirable characteristics of role models, as well as the influence of role models
      in career decisions. Chi-square, Fisher's exact, and Mann-Whitney tests were used
      to assess associations between responses and expressed career choice. RESULTS:
      Thirty of 35 SARRAD participants (85%) plus 103 non-SARRAD participants
      responded. Only 46% felt that there were enough role models at their institutions
      and 56% that there were sufficient role models in academic radiology. More than
      two-thirds of residents surveyed stated that they would be more likely to stay in
      academic radiology if there were more role models. The most desired
      characteristics of role models included availability, enthusiasm, integrity, and
      a positive attitude toward residents. Residents stating that they would choose
      academic careers were more likely to be research track (P = .0001), have more
      publications (P = .01), be less concerned with salary (P = .003), and be less
      concerned about politics (P = .047). Level of debt was not different between
      residents planning to choose academic careers and those with other career plans
      (P = .80). CONCLUSION: Role models in academic radiology play an important role
      in influencing residents to stay in academic radiology. Increasing the number of
      role models in academic radiology with characteristics valued by residents will
      encourage residents to stay in academic medicine.

PMID- 20129273
TI  - Resident duty hour limits: recommendations by the IOM and the response from the
      radiology community.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) set duty hour
      limits across all specialties nationally in 2003 to promote safe patient care and
      resident well-being. At the request of Congress, the Institute of Medicine
      studied the issue of patient safety and resident work hours and recently issued a
      report calling for further restrictions on resident duty hours, better resident
      supervision, and new federal oversight of the ACGME in monitoring resident duty
      hours. The authors review the history behind the current ACGME requirements,
      outline the Institute of Medicine's recommendations, and report on the response
      from the radiology community.

PMID- 20129274
TI  - A reference standard-based quality assurance program for radiology.
AB  - The authors have developed a comprehensive radiology quality assurance (QA)
      program that evaluates radiology interpretations and procedures by comparing them
      with reference standards. Performance metrics are calculated and then compared
      with benchmarks or goals on the basis of published multicenter data and meta
      analyses. Additional workload for physicians is kept to a minimum by having
      trained allied health staff members perform the comparisons of radiology reports
      with the reference standards. The performance metrics tracked by the QA program
      include the accuracy of CT colonography for detecting polyps, the false-negative
      rate for mammographic detection of breast cancer, the accuracy of CT angiography
      detection of coronary artery stenosis, the accuracy of meniscal tear detection on
      MRI, the accuracy of carotid artery stenosis detection on MR angiography, the
      accuracy of parathyroid adenoma detection by parathyroid scintigraphy, the
      success rate for obtaining cortical tissue on ultrasound-guided core biopsies of
      pelvic renal transplants, and the technical success rate for peripheral arterial
      angioplasty procedures. In contrast with peer-review programs, this reference
      standard-based QA program minimizes the possibilities of reviewer bias and
      erroneous second reviewer interpretations. The more objective assessment of
      performance afforded by the QA program will provide data that can easily be used
      for education and management conferences, research projects, and multicenter
      evaluations. Additionally, such performance data could be used by radiology
      departments to demonstrate their value over nonradiology competitors to referring
      clinicians, hospitals, patients, and third-party payers.

PMID- 20129275
TI  - Collaborating with unconventional partners/the embellished letter of
      recommendation.

PMID- 20129276
TI  - A new water scanner designed to collect radiosurgery beam data.

PMID- 20129277
TI  - Show, teach, do.

PMID- 20129278
TI  - Cerebral aneurysms.

PMID- 20129279
TI  - John Loop.

PMID- 20129281
TI  - Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right
      ventricular cardiomyopathy/dysplasia.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is
      a progressive cardiomyopathy showing a wide clinical spectrum in terms of
      clinical expressions and prognoses. OBJECTIVE: This study sought to estimate the
      occurrence of compound and double heterozygotes for mutations in desmosomal
      proteins encoding genes in a cohort of ARVC/D Italian index cases, and to assess
      the clinical phenotype of mutations carriers. METHODS: Fourty-two consecutive
      ARVC/D index cases who fulfilled the International Task Force diagnostic criteria
      were screened for mutations in PKP2, DSP, DSG2, DSC2, and JUP genes by denaturing
      high-performance liquid chromatography (DHPLC) and direct sequencing. RESULTS:
      Three probands (7.1%) showing a family history of sudden death carried multiple
      mutations. Family screening identified an additional 7 multiple-mutation
      carriers. Among the 7 double heterozygotes for mutations in different genes, 2
      were clinically unaffected, 2 were affected, and 3 showed some clinical signs of
      ARVC/D even if they did not fulfill the diagnostic criteria. Two compound
      heterozygotes for mutations in the same gene and 1 subject carrying 3 different
      mutations showed a severe form of the disease with heart failure onset at a young
      age. Moreover, multiple-mutation carriers showed a higher prevalence of left
      ventricular involvement (P = .025) than single-mutation carriers. CONCLUSION:
      Occurrence of compound and double heterozygotes in ARVC/D index cases is
      particularly relevant to mutation screening strategy and to genetic counseling.
      Even if multiple-mutation carriers show a wide variability in clinical
      expression, the extent of the disease is higher compared to that in single
      mutation carriers.

PMID- 20129282
TI  - Mutations in desmosomal protein genes and the pathogenesis of arrhythmogenic
      right ventricular cardiomyopathy.

PMID- 20129284
TI  - Brugada syndrome: lots of questions, some answers.

PMID- 20129285
TI  - The SCN5A gene in Brugada syndrome: mutations, variants, missense and nonsense.
      What's a clinician to do?

PMID- 20129283
TI  - An international compendium of mutations in the SCN5A-encoded cardiac sodium
      channel in patients referred for Brugada syndrome genetic testing.
AB  - BACKGROUND: Brugada syndrome (BrS) is a common heritable channelopathy. Mutations
      in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype.
      OBJECTIVE: This study sought to perform a retrospective analysis of BrS databases
      from 9 centers that have each genotyped >100 unrelated cases of suspected BrS.
      METHODS: Mutational analysis of all 27 translated exons in SCN5A was performed.
      Mutation frequency, type, and localization were compared among cases and 1,300
      ostensibly healthy volunteers including 649 white subjects and 651 nonwhite
      subjects (blacks, Asians, Hispanics, and others) that were genotyped previously.
      RESULTS: A total of 2,111 unrelated patients (78% male, mean age 39 +/- 15 years)
      were referred for BrS genetic testing. Rare mutations/variants were more common
      among BrS cases than control subjects (438/2,111, 21% vs. 11/649, 1.7% white
      subjects and 31/651, 4.8% nonwhite subjects, respectively, P <10(-53)). The yield
      of BrS1 genetic testing ranged from 11% to 28% (P = .0017). Overall, 293 distinct
      mutations were identified in SCN5A: 193 missense, 32 nonsense, 38 frameshift, 21
      splice-site, and 9 in-frame deletions/insertions. The 4 most frequent BrS1
      associated mutations were E1784K (14x), F861WfsX90 (11x), D356N (8x), and G1408R
      (7x). Most mutations localized to the transmembrane-spanning regions. CONCLUSION:
      This international consortium of BrS genetic testing centers has added 200 new
      BrS1-associated mutations to the public domain. Overall, 21% of BrS probands have
      mutations in SCN5A compared to the 2% to 5% background rate of rare variants
      reported in healthy control subjects. Additional studies drawing on the data
      presented here may help further distinguish pathogenic mutations from similarly
      rare but otherwise innocuous ones found in cases.

PMID- 20129286
TI  - Mechanisms that initiate ventricular tachycardia in the infarcted human heart.
AB  - BACKGROUND: Precise mechanisms that initiate ventricular tachycardia (VT) in the
      intact infarcted human heart have not been defined. OBJECTIVE: The purpose of
      this study was to investigate the mechanisms that underlie human postinfarct VT
      initiation. METHODS: Noncontact mapping of the left ventricle was performed in 9
      patients (age 67.1 +/- 7.8 years, ejection fraction 34.4% +/- 5%) with previous
      myocardial infarction and sustained monomorphic VT. RESULTS: Circuits in which
      >/=30% of the diastolic pathway (DP) could be defined were identified in 12 VTs
      (cycle length 357 +/- 60 ms). Eighteen VT episodes were initiated with pacing,
      and one occurred spontaneously. Ten complete and two partial circuits were mapped
      (89% +/- 25% of the DP). In all complete circuits, pacing led to the development
      of unidirectional conduction block at the location of the subsequent VT exit site
      and the formation of functional block creating a border(s) for subsequent DP.
      Wavefront velocity in the DP region slowed from 1.22 +/- 0.2 m/s during sinus
      rhythm to 0.59 +/- 0.14 m/s during VT (P <.005). In 11 initiation episodes, lines
      of functional block and areas of slow conduction developed progressively over one
      to six reentrant cycles before a stable DP was established and sustained
      monomorphic VT ensued. The formation of unidirectional or functional lines of
      block was not identified during identical pacing protocols that failed to
      initiate VT (n = 14). CONCLUSION: Initiation of sustained monomorphic VT requires
      the development of unidirectional block and formation of lines of functional
      block creating borders for a DP in areas of slow conduction. A transitional stage
      often exists during the initiation process before a stable VT circuit is
      established.

PMID- 20129287
TI  - Predicting the unpredictable.

PMID- 20129288
TI  - Fragmented QRS on twelve-lead electrocardiogram predicts arrhythmic events in
      patients with ischemic and nonischemic cardiomyopathy.
AB  - BACKGROUND: Myocardial scar is a substrate for reentrant ventricular arrhythmias
      and is associated with poor prognosis. Fragmented QRS (fQRS) on 12-lead ECG
      represents myocardial conduction delays due to myocardial scar in patients with
      coronary artery disease (CAD). OBJECTIVE: The purpose of this study was to
      determine whether fQRS is associated with increased ventricular arrhythmic event
      and mortality in patients with CAD and nonischemic dilated cardiomyopathy (DCM).
      METHODS: Arrhythmic events and mortality were studied in 361 patients (91% male,
      age 63.3 +/- 11.4 years, mean follow-up 16.6 +/- 10.2 months) with CAD and DCM
      who received an implantable cardioverter-defibrillator for primary or secondary
      prophylaxis. fQRS included various RSR' patterns (QRS duration <120 ms), such as
      > or =1 R prime or notching of the R wave or S wave present on at least two
      contiguous leads of those representing anterior (V(1)-V(5)), lateral (I, aVL,
      V(6)), or inferior (II, III, aVF) myocardial segments. RESULTS: fQRS was present
      in 84 (23%) patients (fQRS group) and absent in 100 (28%) patients (non-fQRS
      group). Wide QRS (wQRS; QRS duration > or =120 ms) was present in 177 (49%)
      patients. Kaplan-Meier analysis revealed that event-free survival for an
      arrhythmic event (implantable cardioverter-defibrillator shock or antitachycardia
      pacing) was significantly lower in the fQRS group than in the non-fQRS and wQRS
      groups (P <.001 and P <.019, respectively). fQRS was an independent predictor of
      an arrhythmic event but not of death. CONCLUSION: fQRS on 12-lead ECG is a
      predictor of arrhythmic events in patients with CAD and DCM. fQRS is associated
      with a significantly decreased time to first arrhythmic event compared with non
      fQRS and wQRS.

PMID- 20129289
TI  - Yin and yang of the cardiac pacemaker clock system in health and disease.

PMID- 20129290
TI  - In vitro tests reveal sample radiofrequency identification readers inducing
      clinically significant electromagnetic interference to implantable pacemakers and
      implantable cardioverter-defibrillators.
AB  - BACKGROUND: The use of radiofrequency identification (RFID) systems is expanding
      and highlights the need to address electromagnetic interference (EMI) to
      implantable pacemakers and implantable cardioverter-defibrillators (ICDs).
      OBJECTIVE: This study sought to examine the electromagnetic compatibility (EMC)
      between RFID readers and implantable pacemakers or ICDs. METHODS: During in vitro
      testing, 15 implantable pacemakers and 15 ICDs were exposed to 13 passive RFID
      readers in 3 frequency bands: 134 kHz (low frequency [LF]), 13.56 MHz (high
      frequency [HF]), and 915 MHz (ultra high frequency [UHF]). RESULTS: While being
      exposed to LF RFID, a reaction was observed for 67% of all pacemaker tests
      (maximum distance 60 cm) and 47% of all ICD tests (maximum distance 40 cm).
      During HF RFID exposure, a reaction was observed for 6% of all pacemaker tests
      (maximum distance 22.5 cm) and 1% of all ICD tests (maximum distance 7.5 cm). For
      both pacemakers and ICDs, no reactions were observed during exposure to UHF RFID
      or continuous-wave RFID. Pacemakers and ICDs were most susceptible to modulated
      LF RFID readers. CONCLUSION: Although there is in vitro testing evidence for
      concern for implantable pacemaker and ICD EMI at LF and HF, the FDA has not
      received any incident reports of pacemaker or ICD EMI caused by any RFID system.
      We do not believe the current situation reveals an urgent public health risk.

PMID- 20129291
TI  - Noise you can't hear.

PMID- 20129292
TI  - Induction of atrial ectopic beats with calcium release inhibition: Local
      hierarchy of automaticity in the right atrium.
AB  - BACKGROUND: Recent evidence indicates that spontaneous sarcoplasmic reticulum
      (SR) calcium (Ca) release underlies the mechanism of sinoatrial node (SAN)
      acceleration during beta-stimulation, indicating the importance of the Ca clock
      in SAN automaticity. Whether or not the same mechanism applies to atrial ectopic
      pacemakers (AEPs) remains unclear. OBJECTIVE: The purpose of this study was to
      assess the mechanism of AEP. METHODS: We simultaneously mapped intracellular
      calcium (Ca(i)) and membrane potential in 12 isolated canine right atria. The
      late diastolic Ca(i) elevation (LDCAE) was used to detect the Ca clock activity.
      Pharmacological interventions with isoproterenol (ISO), ryanodine, and ZD7288, a
      blocker of the I(f) membrane current, were performed. RESULTS: Ryanodine, which
      inhibits SR Ca release, reduced LDCAE in SAN, resulting in an inferior shift of
      the pacemaking site. Cycle length increased significantly in a dose-dependent
      way. In the presence of 3 to 10 mumol/l of ryanodine, ISO infusion consistently
      induces AEPs from the lower crista terminalis. All ectopic beats continuing over
      30 seconds were located at the lower crista terminalis. These AEPs were resistant
      to ryanodine treatment even at high doses. Subsequent blockade of I(f) inhibited
      the AEP and resulted in profound bradycardia. CONCLUSION: Spontaneous SR Ca
      release underlies ISO-induced increase of superior SAN activity. As compared with
      SAN, the AEP is less dependent on the Ca clock and more dependent on the membrane
      clock for its automaticity. AEPs outside the SAN can effectively serve as backup
      pacemakers when the Ca clock functionality is reduced.

PMID- 20129293
TI  - Inadvertent electrical isolation of the left atrial appendage during catheter
      ablation of persistent atrial fibrillation.
AB  - BACKGROUND: Left atrial appendage (LAA) isolation is rare and may be associated
      with impaired transport function and thromboembolism. OBJECTIVE: The purpose of
      this study was to determine the mechanisms of inadvertent isolation of the LAA
      during atrial fibrillation (AF) ablation. METHODS: This study consisted of 11
      patients (ejection fraction 0.43 +/- 0.18, left atrial diameter 51 +/- 8 mm) with
      persistent AF who had LAA conduction block during a procedure for AF (n = 8) or
      atrial tachycardia (AT) (n = 3). RESULTS: LAA conduction block occurred during
      ablation at the Bachmann bundle region in 6 patients, mitral isthmus in 3, LAA
      base in 2, and coronary sinus in 1. The mean distance from the ablation site to
      the LAA base was 5.0 +/- 1.9 cm. LAA isolation was transient in all 6 patients in
      whom LAA conduction was monitored and was permanent in the 4 patients in whom
      conduction was not monitored during energy delivery. The remaining patient was
      noted to have LAA isolation during a redo procedure before any ablation. Nine of
      (82%) the 11 patients have remained arrhythmia-free without antiarrhythmic drugs
      at mean follow-up of 6 +/- 7 months, and all have continued taking warfarin.
      CONCLUSION: Electrical isolation of the LAA may occur during ablation of
      persistent AF and AT even when the ablation site is remote from the LAA. This
      likely is due to disruption of the Bachmann bundle and its leftward extension,
      which courses along the anterior left atrium and bifurcates to surround the LAA.
      Monitoring of LAA conduction during ablation of persistent AF or AT is important
      in avoiding permanent LAA isolation.

PMID- 20129294
TI  - The isolated appendage: a new victim of collateral damage during atrial
      fibrillation ablation?

PMID- 20129295
TI  - Characterization of conduction recovery after pulmonary vein isolation using the
      "single big cryoballoon" technique.
AB  - BACKGROUND: Pulmonary vein isolation using the cryoballoon technique (CB-PVI) has
      evolved into a simple and safe alternative for point-by-point radiofrequency
      ablation. Systematic analysis of conduction recovery occurring after CB-PVI and
      causing recurrent atrial fibrillation has not yet been performed. OBJECTIVE: The
      purpose of this study was to analyze conduction recovery after PVI using the
      single big (28-mm) cryoballoon technique. METHODS: Twenty-six patients with
      recurrent atrial tachyarrhythmia after previous CB-PVI underwent repeat ablation.
      Pulmonary vein (PV) reisolation was performed by antral irrigated radiofrequency
      ablation using electroanatomic mapping. For analysis of the location of
      conduction gaps, the ipsilateral LA-PV junction was divided into six equally
      distributed segments. RESULTS: PV reconduction frequently occurred into multiple
      (>2) PVs (54% patients). Conduction gaps could be abolished by single point
      ablation in 63% (lateral) and 41% (septal) of patients or by incomplete circular
      lesions in the remaining patients. A significantly higher number of patients
      exhibited conduction recovery at inferior segments (85% lateral, 77% septal)
      compared with superior segments (42% lateral, 31% septal). Furthermore, the ridge
      between PV ostia and left atrial appendage (LAA) was highly associated with
      reconduction into lateral PVs (81% of patients). Retrospective analysis of the
      initial CB-PVI-procedure revealed lower freezing temperatures at superior than
      inferior PVs as well as sharp catheter angulations with loss of central
      cryoballoon alignment to reach inferior PVs. CONCLUSION: Conduction recovery
      after CB-PVI occurs at a high incidence at inferior sites around ipsilateral PV
      ostia and the LAA-PV ridge. Modifications of the technique to ensure optimal
      balloon-tissue contact at predilection sites may improve long-term success rates.

PMID- 20129296
TI  - Pulmonary vein reconnection after cryoballoon ablation: back to the drawing
      board.

PMID- 20129297
TI  - Diagnostic utility of bipolar precordial leads during ajmaline testing for
      suspected Brugada syndrome.
AB  - BACKGROUND: Leads V(1) and V(2) recorded from the standard position (fourth
      intercostal space) have insufficient sensitivity to detect the diagnostic type 1
      Brugada ECG pattern. OBJECTIVE: The purpose of this study was to compare the
      sensitivity of bipolar leads with a positive pole at V(2) and a negative pole at
      V(4) or V(5) with that of the standard unipolar lead V(2) for detection of the
      type 1 Brugada pattern. METHODS: We analyzed digital 15-lead ECGs (12 standard
      leads plus leads V(1) to V(3) recorded from the third intercostal space [V(1h) to
      V(3h)]) acquired during diagnostic ajmaline testing in 128 patients (80 men, age
      37 +/- 15 years) with suspected Brugada syndrome and standard 12-lead ECGs
      recorded in 229 healthy subjects (111 men, age 33 +/- 4 years). Bipolar leads
      between V(2) (positive pole) and V(4) or V(5) (leads V(2-4), V(2-5)) were derived
      by subtracting leads V(4) and V(5) from V(2). All ECGs were examined for the
      presence of type 1 Brugada pattern. RESULTS: During 21 (16.4%) positive ajmaline
      tests, type 1 pattern was observed in lead V(2h) during 20 tests (95.2%) and in
      V(2) during 10 tests (47.6%). Type 1 pattern appeared in lead V(2-4) or V(2-5) in
      all tests when it was present in V(2) and in seven tests during which it was
      observed in lead V(2h) but not V(2) (17 tests [81%]). Type 1-like pattern was
      observed in lead V(2-4) or V(2-5) during two nonpositive tests (1.9%) and in one
      healthy subject (0.4%). CONCLUSION: Bipolar leads V(2-4) and V(2-5) are more
      sensitive than lead V(2) for detection of the type 1 Brugada pattern.

PMID- 20129298
TI  - Atrial electrophysiological and structural remodeling in high-risk patients with
      Brugada syndrome: assessment with electrophysiology and echocardiography.
AB  - BACKGROUND: Atrial fibrillation (AF) often occurs in Brugada syndrome (BrS), and
      BrS patients with spontaneous AF often experience ventricular fibrillation (VF)
      attacks. Atrial vulnerability providing a substrate for AF is known to be
      enhanced in BrS, but there are no data on atrial structural attributes.
      OBJECTIVE: The objective of this study was to assess atrial electrophysiological
      and structural characteristics in BrS and their relationships with gene
      mutations. METHODS: We studied 57 patients with BrS. Intra-atrial conduction time
      (CT) was defined as the interval from the stimulus at the high right atrium to
      atrial deflection at the distal portion of the coronary sinus. Left atrial volume
      index (LAVI) was measured by the modified Simpson method at left ventricular end
      systole using echocardiography. SCN5A mutations were analyzed in all patients.
      RESULTS: In patients with documented VF, spontaneous AF frequently occurred and
      prolonged CT and increased LAVI were observed compared with those in patients
      without VF (all P < .05; LAVI: 22 +/- 5 vs. 32 +/- 7 ml/m(2)). Even among
      patients without AF, CT and LAVI were still increased in patients with VF (all P
      < .05; LAVI: 22 +/- 5 vs. 29 +/- 5 ml/m(2)). The presence of SCN5A mutation was
      associated with prolonged CT (P < .05) and increased LAVI (P < .01), but not with
      arrhythmic episodes. CONCLUSION: Both atrial vulnerability and structural
      remodeling are enhanced in high-risk patients with BrS, even in those without AF.
      These morphological characteristics suggest that BrS is a form of genetic
      myocardial disease.

PMID- 20129299
TI  - Attenuated recovery of heart rate turbulence early after myocardial infarction
      identifies patients at high risk for fatal or near-fatal arrhythmic events.
AB  - BACKGROUND: Autonomic dysfunction tends to improve over time after acute
      myocardial infarction (MI), but the clinical significance of autonomic remodeling
      is not well known. OBJECTIVE: The purpose of this study was to test the
      hypothesis that the amount of recovery of autonomic function early after MI is
      associated with a risk for serious arrhythmias. METHODS: The prognostic
      significance of autonomic remodeling after MI was assessed in one post-MI cohort
      [Cardiac Arrhythmia and Risk Stratification after Myocardial Infarction
      (CARISMA)] and validated in a second cohort [Risk Estimation After Infarction,
      Noninvasive Evaluation (REFINE)]. Changes in heart rate variability (DeltaHRV)
      and heart rate turbulence (DeltaHRT) were measured from 24-hour ECG recordings
      performed early (5-21 days) and later (6 weeks) after MI in CARISMA (n = 312).
      DeltaHRV and DeltaHRT were similarly measured from early (2-4 weeks) and later
      (10-14 weeks) post-MI recordings in REFINE (n = 322). RESULTS: HRV and HRT
      increased over time in both cohorts. Attenuated recovery of autonomic function,
      defined as DeltaHRT slope <2.0 ms/RR, was associated with a 9.4-fold (95%
      confidence interval 1.2-71.6; P = .03) higher risk of ECG-documented sustained
      ventricular tachycardia or ventricular fibrillation in CARISMA and a 7.0-fold
      (95% confidence interval 1.6-29.6; P = .009) higher risk of fatal or near-fatal
      events in REFINE. Changes in HRV and HRT were not predictive of nonarrhythmic
      death in either cohort. CONCLUSION: Attenuated recovery of autonomic function
      early after MI consistently predicts a higher risk of fatal or near-fatal
      arrhythmic events. A lack of improvement in HRT early after MI appears to be a
      specific marker for serious arrhythmic events.

PMID- 20129300
TI  - A new specific risk marker for postmyocardial infarction fatal arrhythmias:
      significance of attenuated recovery of baroreflex sensitivity.

PMID- 20129301
TI  - How the heart can fibrillate: when diversity is a disadvantage.

PMID- 20129302
TI  - Avoidance of left phrenic nerve injury during endocardial ventricular tachycardia
      substrate modification.

PMID- 20129304
TI  - Gluttony and obesity.

PMID- 20129303
TI  - Comparison of 30-day outcomes after non-LapBand primary and revisional bariatric
      surgical procedures from the Longitudinal Assessment of Bariatric Surgery study.
AB  - BACKGROUND: The goals were to compare the morbidity and mortality between primary
      and revisional bariatric surgery and to identify the clinical predictors of
      adverse outcomes among patients undergoing revisional surgery in the Longitudinal
      Assessment of Bariatric Surgery consortium. The study was multi-institutional at
      university hospitals in the United States. METHODS: Data from the LABS-1 (safety)
      cohort were analyzed, excluding primary gastric banding patients. A total of 3802
      LABS-1 patients were included: 3577 who underwent primary surgery and 225 who
      underwent revisional surgery. The demographic, clinical, operative, and 30-day
      outcome data were compared between the 2 groups. A nonlinear mixed effects logit
      model was used to identify independent risk factors for adverse outcomes (death,
      deep vein thrombosis, pulmonary embolism, reintubation, reoperation, or discharge
      after 30 days). RESULTS: Compared with those undergoing revisional surgery, the
      primary surgery patients were younger (median age 44 versus 49 years, P <.0001)
      and more likely to be male (20.5% versus 12.7%, P = .006) and heavier (median
      body mass index 47.3 versus 41.2 kg/m(2), P <.0001) and to have more co
      morbidities (P <.0001), including hypertension (56.0% versus 46.0%, P = .0044),
      diabetes (35.7% versus 20.0%, P <.0001), and sleep apnea (50.3% versus 27.2%, P
      <.0001). The operative time for the revisional procedures was longer (median 181
      versus 135 min, P <.0001) and associated with greater blood loss (median 100
      versus <50 mL, P <.0001). Adverse outcomes were more likely after revisional
      surgery (15.1% versus 5.3%, P <.0001, odds ratio 2.4, 95% confidence interval 1.6
      3.6). After adjusting for patient characteristics previously shown to be
      associated with adverse outcomes, this difference remained statistically
      significant (odds ratio 2.3, 95% confidence interval 1.5-3.8). The 30-day
      mortality rate was similar in the 2 groups (.4%). CONCLUSION: Revisional surgery
      was performed without substantial mortality but with a greater incidence of
      adverse outcomes than was primary bariatric surgery.

PMID- 20129305
TI  - The new pandemic: SuperStress?

PMID- 20129306
TI  - The Lost Symbol sparks nationwide interest in the noetic sciences.

PMID- 20129307
TI  - Trends that will affect your future ... Mr South Whidbey, globalization, and the
      worship of profit.
AB  - The SchwartzReport tracks emerging trends that will affect the world,
      particularly the United States. For EXPLORE it focuses on matters of health in
      the broadest sense of that term, including medical issues, changes in the
      biosphere, technology, and policy considerations, all of which will shape our
      culture and our lives.

PMID- 20129308
TI  - Medicine can give me a diagnosis, and faith can give me a different prognosis:
      faith and healing in the American South.

PMID- 20129309
TI  - Attitudes and interests toward research among students at two colleges of
      acupuncture and Oriental medicine.
AB  - BACKGROUND: Collaborative input from clinicians of acupuncture and Oriental
      medicine (AOM) is required for sound AOM research, and AOM training institutions
      have begun to include research education into their curriculum. However, few
      attempts have been made to systematically evaluate AOM practitioners'
      perspectives on the value of research to their profession. METHODS: We conducted
      surveys of AOM students at two institutions that have begun to integrate research
      training into their curriculum, the New England School of Acupuncture and the
      Oregon College of Oriental Medicine. Surveys were conducted to assess current
      attitudes regarding the value of research and to serve as a reference point for
      documenting the impact of ongoing research training programs on these attitudes.
      Surveys at both institutions were independently developed and administered but
      shared seven questions that were phrased very similarly. This paper summarizes
      responses to these questions. RESULTS: Surveys at both institutions suggest
      interest in research among AOM students is high in first-year students; students
      in later years showed a lower level of interest, but the cross-sectional design
      of this survey does not allow any temporal effects to be inferred. Results also
      indicate that AOM students believe research is highly relevant to how both the
      public and the health insurance industry view their system of healthcare but not
      highly relevant to their own clinical practice of AOM. The belief that research
      is of limited relevance to clinical practice was associated with widespread
      belief that scientific methods may not be consistent with the principles of AOM.
      CONCLUSIONS: Results of these surveys provide important preliminary information
      about attitudes of AOM students toward research, and thus the value and future
      specific needs of research training programs targeting this population. Repeated
      implementation of validated versions of our surveys are needed to confirm the
      trends we report and to evaluate the impact of research training programs already
      in place on AOM students' attitudes toward research.

PMID- 20129311
TI  - Chiropractic care of a pediatric patient with migraine-type headaches: a case
      report and selective review of the literature.

PMID- 20129312
TI  - Integrative men's nutrition.

PMID- 20129313
TI  - Implementing OHEs.

PMID- 20129310
TI  - Top-down and bottom-up mechanisms in mind-body medicine: development of an
      integrative framework for psychophysiological research.
AB  - It has become increasingly evident that bidirectional ("top-down and bottom-up")
      interactions between the brain and peripheral tissues, including the
      cardiovascular and immune systems, contribute to both mental and physical health.
      Therapies directed toward addressing functional links between mind/brain and body
      may be particularly effective in treating the range of symptoms associated with
      many chronic diseases. In this paper, we describe the basic components of an
      integrative psychophysiological framework for research aimed at elucidating the
      underlying substrates of mind-body therapies. This framework recognizes the
      multiple levels of the neuraxis at which mind-body interactions occur. We
      emphasize the role of specific fronto-temporal cortical regions in the
      representation and control of adverse symptoms, which interact reciprocally with
      subcortical structures involved in bodily homeostasis and responses to stress.
      Bidirectional autonomic and neuroendocrine pathways transmit information between
      the central nervous system and the periphery and facilitate the expression of
      affective, autonomic, hormonal, and immune responses. We propose that heart rate
      variability (HRV) and markers of inflammation are important currently available
      indices of central-peripheral integration and homeostasis within this homeostatic
      network. Finally, we review current neuroimaging and psychophysiological research
      from diverse areas of mind-body medicine that supports the framework as a basis
      for future research on the specific biobehavioral mechanisms of mind-body
      therapies.

PMID- 20129314
TI  - The continuing bias against complementary and integrative healthcare education.

PMID- 20129315
TI  - Classical and modern measurement theories, patient reports, and clinical
      outcomes.

PMID- 20129316
TI  - Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled
      trial.
AB  - OBJECTIVE: To investigate the effect of a medical food on cognitive function in
      people with mild Alzheimer's disease (AD). METHODS: A total of 225 drug-naive AD
      patients participated in this randomized, double-blind controlled trial. Patients
      were randomized to active product, Souvenaid, or a control drink, taken once
      daily for 12 weeks. Primary outcome measures were the delayed verbal recall task
      of the Wechsler Memory Scale-revised, and the 13-item modified Alzheimer's
      Disease Assessment Scale-cognitive subscale at week 12. RESULTS: At 12 weeks,
      significant improvement in the delayed verbal recall task was noted in the active
      group compared with control (P = .021). Modified Alzheimer's Disease Assessment
      Scale-cognitive subscale and other outcome scores (e.g., Clinician Interview
      Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric
      Inventory, Alzheimer's disease Co-operative Study-Activities of Daily Living,
      Quality of Life in Alzheimer's Disease) were unchanged. The control group neither
      deteriorated nor improved. Compliance was excellent (95%) and the product was
      well tolerated. CONCLUSIONS: Supplementation with a medical food including
      phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal
      recall) in mild AD patients. This proof-of-concept study justifies further
      clinical trials.

PMID- 20129317
TI  - Outcome over seven years of healthy adults with and without subjective cognitive
      impairment.
AB  - BACKGROUND: Subjective cognitive impairment (SCI) in older persons without
      manifest symptomatology is a common condition with a largely unclear prognosis.
      We hypothesized that (1) examining outcome for a sufficient period by using
      conversion to mild cognitive impairment (MCI) or dementia would clarify SCI
      prognosis, and (2) with the aforementioned procedures, the prognosis of SCI
      subjects would differ significantly from that of demographically matched healthy
      subjects, free of SCI, termed no cognitive impairment (NCI) subjects. METHODS: A
      consecutive series of healthy subjects, aged > or =40 years, presenting with NCI
      or SCI to a brain aging and dementia research center during a 14-year interval,
      were studied and followed up during an 18-year observation window. The study
      population (60 NCI, 200 SCI, 60% female) had a mean age of 67.2 +/- 9.1 years,
      was well-educated (mean, 15.5 +/- 2.7 years), and cognitively normal (Mini-Mental
      State Examination, 29.1 +/- 1.2). RESULTS: A total of 213 subjects (81.9% of the
      study population) were followed up. Follow-up occurred during a mean period of
      6.8 +/- 3.4 years, and subjects had a mean of 2.9 +/- 1.6 follow-up visits. Seven
      NCI (14.9%) and 90 SCI (54.2%) subjects declined (P < .0001). Of NCI decliners,
      five declined to MCI and two to probable Alzheimer's disease. Of SCI decliners,
      71 declined to MCI and 19 to dementia diagnoses. Controlling for baseline
      demographic variables and follow-up time, Weibull proportional hazards model
      revealed increased decline in SCI subjects (hazard ratio, 4.5; 95% confidence
      interval, 1.9-10.3), whereas the accelerated failure time model analysis with an
      underlying Weibull survival function showed that SCI subjects declined more
      rapidly, at 60% of the rate of NCI subjects (95% confidence interval, 0.45-0.80).
      Furthermore, mean time to decline was 3.5 years longer for NCI than for SCI
      subjects (P = .0003). CONCLUSIONS: These results indicate that SCI in subjects
      with normal cognition is a harbinger of further decline in most subjects during a
      7-year mean follow-up interval. Relevance for community populations should be
      investigated, and prevention studies in this at-risk population should be
      explored.

PMID- 20129318
TI  - Toward an Alzheimer's disease diagnosis via high-resolution blood gene
      expression.
AB  - BACKGROUND: There is a significant need for reliable molecular biomarkers to aid
      in Alzheimer's disease (AD) clinical diagnosis. METHODS: We performed a genome
      wide investigation of the human transcriptome, taking into account the
      discriminatory power of splice variations from the blood of 80 AD patients and 70
      nondemented control (NDC) individuals. RESULTS: We characterized a blood RNA
      signature composed of 170 oligonucleotide probe sets associated with 133 genes
      that can correctly distinguish AD patients from NDC with a sensitivity of 100%
      and specificity of 96%. Functionally, this signature highlights genes involved in
      pathways that were associated with macrophages and lymphocytes within AD
      patients: Transforming growth factor (TGF-beta) signaling, oxidative stress,
      innate immunity and inflammation, cholesterol homeostasis, and lipid-raft
      perturbation, whereas other genes may also provide new insights in the biology of
      AD. CONCLUSIONS: This study provides proof-of-concept that whole-blood profiling
      can generate an AD-associated classification signature via the specific relative
      expression of biologically relevant RNAs. Such a signature will need to be
      validated with extended patient cohorts, and evaluated to learn whether it can
      differentiate AD from others types of dementia.

PMID- 20129319
TI  - White matter integrity and cortical metabolic associations in aging and dementia.
AB  - BACKGROUND: Studies show that white matter hyperintensities, regardless of
      location, primarily affect frontal lobe metabolism and function. This report
      investigated how regional white matter integrity (measured as fractional
      anisotropy [FA]) relates to brain metabolism, to unravel the complex relationship
      between white matter changes and brain metabolism. OBJECTIVE: To elucidate the
      relationship between white matter integrity and gray matter metabolism using
      diffusion tensor imaging and fluorodeoxyglucose-positron emission tomography in a
      cohort of 16 subjects ranging from normal to demented (age, >55 years). METHODS:
      Mean FA values from white matter regions underlying the medial prefrontal,
      inferior-lateral prefrontal, parietal association, and posterior temporal areas
      and the corpus callosum were regressed with glucose metabolism (by positron
      emission tomography), using statistical parametric mapping (P < 0.005; voxel
      cluster, >100). Regional cerebral glucose metabolism was the primary outcome
      measure. According to our hypothesis, those hypometabolic cortical regions
      affected by Alzheimer's disease would correlate with a lower FA of associated
      tracks. RESULTS: Our data show inter-regional positive correlations between FA
      and gray matter metabolism for the prefrontal cortex, temporal, and parietal
      regions. Our results suggest that left prefrontal FA is associated with left
      temporal and parietal metabolism. Further, left posterior temporal FA correlated
      with left prefrontal metabolism. Finally, bilateral parietal FA correlated with
      bilateral temporal metabolism. CONCLUSIONS: These regions are associated with
      cognitive processes affected in Alzheimer's disease and cerebrovascular disease,
      suggesting a link with white matter degeneration and gray matter hypometabolism.
      Therefore, cortical function and white matter degeneration are related in aging
      and dementia.

PMID- 20129320
TI  - Subtypes of depression among patients with Alzheimer's disease and other
      dementias.
AB  - OBJECTIVES: We compared the prevalence of subtypes of depression in patients with
      Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia (UD).
      METHODS: Using the Integrated Healthcare Information Services database, we
      conducted an analysis of subtypes of depression (major depressive disorder,
      depressive disorder not otherwise specified, dysthymic disorder; depressive
      psychosis, and adjustment disorder depressive) among patients with AD, VaD, and
      UD. Six thousand four hundred and forty patients aged 60 years or older with
      dementia (2947 with AD, 725 with VaD, and 2768 with UD) were identified from
      January 1 to December 31, 2001. Both subtypes of depression and dementia
      subgroups were diagnosed using criteria from the International Classification of
      Diseases, 9th version. RESULTS: The overall prevalence of depressive disorders
      was 27.41%. The prevalence of depressive disorders was significantly higher in
      VaD (44.14%) and UD (32.48%) patients compared with AD (18.53%, P < .0001)
      patients. The AD patients had the lowest prevalence of all subtypes of
      depression. The VaD patients, compared with both AD and UD (P < .005), had a
      significantly higher prevalence of: 1) depressive disorder not otherwise
      specified, 2) major depressive disorder, and 3) dysthymic disorder. Adjustment
      disorder with depressive symptoms was more common in the UD subgroup, whereas the
      rate of depressive psychosis was similar in all dementia subgroups CONCLUSIONS:
      This study supports the view that depressive disorders are more prevalent in VaD
      compared with UD and AD, and provides indicators to the clinician for further
      evaluation of depression in dementia subgroups.

PMID- 20129321
TI  - Rivastigmine for the treatment of dementia in patients with progressive
      supranuclear palsy: Clinical observations as a basis for power calculations and
      safety analysis.
AB  - Cognitive decline and dementia are present in about 50% of patients with
      progressive supranuclear palsy (PSP). Based on the known involvement of the
      cholinergic system in PSP patients, and because rivastigmine, in contrast to
      other cholinesterase inhibitors, inhibits both acetylcholinesterase and
      butyrylcholinesterase, we discuss clinical observations of five patients
      suffering from PSP and dementia who were all treated with rivastigmine over a
      period of 3 to 6 months. We found a slight improvement in specific cognitive
      function that may justify further controlled studies. A calculation of sample
      size revealed that a study on the effect of rivastigmine in PSP should include
      about 31 patients to detect a significant effect. In subtests, meaningful results
      can be obtained with even lower numbers (five patients for a verbal fluency test,
      and 14 patients for a logical memory task).

PMID- 20129322
TI  - Early dementia diagnosis and the risk of suicide and euthanasia.
AB  - BACKGROUND: Diagnosis of dementia is occurring earlier, and much research
      concerns the identification of predementia states and the hunt for biomarkers of
      Alzheimer's disease. Reports of suicidal behavior and requests for euthanasia in
      persons with dementia may be increasing. METHODS: We performed a selective
      literature review of suicide risk in persons with dementia and the ethical issues
      associated with euthanasia in this population. RESULTS: In the absence of any
      effective treatments for Alzheimer's disease or other types of dementia, there is
      already evidence that persons with mild cognitive change and early dementia are
      at risk of suicidal behavior, often in the context of comorbid depression. The
      ensuing clinical, ethical, and legal dilemmas associated with physician-assisted
      suicide and euthanasia in the context of dementia are a subject of intense
      debate. By analogy, the preclinical and early diagnoses of Huntington's disease
      are associated with an increased risk of suicidal behavior. Thus there is the
      potential for a preclinical and early diagnosis of Alzheimer's disease (through
      biomarkers, neuroimaging, and clinical assessment) to result in increased suicide
      risk and requests for physician-assisted suicide. CONCLUSIONS: Although dementia
      specialists have long recognized the importance of a sensitive approach to
      conveying bad news to patients and families and the possibility of depressive
      reactions, suicidal behavior has not been regarded as a likely outcome. Such
      preconceptions will need to change, and protocols to monitor and manage suicide
      risk will need to be developed for this population.

PMID- 20129323
TI  - Alzheimer's disease and infection: Do infectious agents contribute to progression
      of Alzheimer's disease?

PMID- 20129325
TI  - AAGL practice report: practice guidelines for management of intrauterine
      synechiae.

PMID- 20129326
TI  - Practical guide to laparoscopic pain mapping.
AB  - Conscious laparoscopic pain mapping, a technique that has been described in the
      literature for more than a decade, can be a particularly helpful tool to assist
      with pelvic pain diagnosis and treatment decisions. Several factors, when
      optimized, increase the likelihood of a good outcome. Herein, we review the
      literature and address common questions about pain mapping including appropriate
      patient selection, standard technique, typical outcomes, and how the results
      might influence treatment.

PMID- 20129327
TI  - Transcervical embryoscopy: images of first-trimester missed abortion.

PMID- 20129328
TI  - Nerve-sparing laparoscopic radical excision of deep endometriosis with rectal and
      parametrial resection.

PMID- 20129329
TI  - Hysteroscopic appearance of endometrial cavity after microwave endometrial
      ablation.
AB  - STUDY OBJECTIVE: To assess the appearance of the endometrial cavity after
      microwave endometrial ablation. DESIGN: Prospective observational study. SETTING:
      GuangDong Women's and Children's Hospital, GuangDong, China. PATIENTS: A total of
      349 patients who underwent microwave endometrial ablation from January 2000
      through August 2008 were followed up for 1 month to 8 years. At follow-up in 2007
      and 2008, patients were advised of this clinical study and were randomly selected
      for participation if they agreed to undergo outpatient hysteroscopy to assess the
      uterine cavity during follow-up visits. Fifty three patients (median [range] age,
      43.1 [33-53] years) were recruited into the study at the time of endometrial
      ablation. INTERVENTION: Outpatient hysteroscopy. MAIN RESULTS: Within the first 3
      months after ablation, outpatient hysteroscopy revealed varying amounts of
      necrotic tissue from the endometrium and superficial myometrium of the uterus.
      Six months postablation, a granulomatous reaction and fibrosis were present. A
      fibrotic cavity was also evident, and menstrual flow was reduced or had ceased.
      One year after ablation, hysteroscopy demonstrated a fibrotic cavity with
      myofibrous scars. Most patients developed amenorrhea at this time. Two years or
      more postablation, a second hysteroscopy demonstrated various types of
      intrauterine adhesions in 28 of the 53 women (52.8%). A cervical adhesion was
      observed in 1 patient (1.9%), focal adhesions in the fundal area in 12 (22.6%), a
      narrowed and scarred uterine cavity with bilateral stenotic tubal ostia in 11
      (20.7%), and complete obliteration of the cavity in 4 (7.5%). Of these 28 women,
      22 had amenorrhea, 3 had vaginal spotting during menstruation, and 2 had
      hypomenorrhea. Of those without intrauterine adhesions, only 5 had amenorrhea, 10
      had vaginal spotting, and 8 had hypomenorrhea. CONCLUSION: The hysteroscopic
      appearance of the uterine cavity after microwave endometrial ablation varies
      considerably. In this study, the menstrual outcome was correlated with
      postablation uterine cavity appearance.

PMID- 20129330
TI  - Laparoscopic nerve-sparing radical trachelectomy: surgical technique and outcome.
AB  - STUDY OBJECTIVE: To assess the feasibility of the laparoscopic approach in
      fertility-preserving and radical surgery of cervical cancer in young patients.
      DESIGN: Retrospective study (Canadian Task Force classification I). SETTING:
      Hospital Son Llatzer, Palma de Mallorca, Spain. PATIENTS: Nine women with early
      cervical cancer. INTERVENTION: Laparoscopic nerve-sparring radical trachelectomy.
      MEASUREMENTS AND MAIN RESULTS: Data for 9 consecutive women undergoing
      laparoscopic nerve-sparing radical trachelectomy because of FIGO IA2 (n=2) or
      FIGO IB1 (n=7) infiltrating cervical carcinoma of the squamous type (n=6) or
      adenocarcinoma (n=3) were analyzed. Resection of the pericervical ligaments was
      laparoscopically performed, preserving innervation of the bladder and the
      arterial supply of the uterus. The laparoscopic approach enabled completion of
      the operation via the vaginal route without difficulties. The mean duration of
      surgery was 270 minutes. No relevant perioperative complications occurred. Two
      women became pregnant: 1 underwent an elective cesarean section delivery at week
      38, and hysterectomy was performed 6 months later; and the other woman was
      pregnant at the time of this writing. Mean duration of follow-up was 28 months.
      Six patients currently have regular menses without evidence of disease. One
      patient had a central recurrence at 14 months, which was treated using surgery
      and radiochemotherapy, and she was free of disease at the last follow-up.
      CONCLUSIONS: Laparoscopic nerve-sparring radical trachelectomy may be an
      alternative in fertility-preserving surgery for cervical cancer in centers in
      which specialization in radical vaginal surgery is lacking. The procedure enables
      preservation of autonomic innervation of the urinary bladder and the arterial
      supply of the uterus.

PMID- 20129331
TI  - Surgical treatment of endometriosis in private practice: cohort study with mean
      follow-up of 3 years.
AB  - STUDY OBJECTIVE: To describe our experience with surgical treatment of
      endometriosis. DESIGN: Observational cohort study (Canadian Task Force
      classification II-2). SETTING: Private hospital. PATIENTS: One hundred sixty
      three patients with histologically confirmed endometriosis who had completed a
      preoperative questionnaire, had available intraoperative findings and
      photographic documentation, and had been followed up to 6 years. INTERVENTION:
      Laparoscopic electrosurgical excision of endometriotic implants. MEASUREMENTS AND
      MAIN RESULTS: Patients completed a visual analogue scale (VAS) for 6 components
      of endometriosis-related symptoms. The EuroQol Group EQ-5D questionnaire was used
      for evaluation of quality of life. Long-term follow up was performed using a
      questionnaire and review of patient medical records. Mean (SD; 95% confidence
      interval) patient age at surgery was 31.01 (8.5; 29.7-32.3) years. The primary
      symptom at initial consultation was dysmenorrhea in 94 patients (57.67%,
      nonmenstrual pelvic pain in 44 (27%), dyspareunia in 11 (6.75%), menorrhagia in 8
      (4.9%), infertility in 4 (2.45%), and pelvic mass in 2 (1.23%). Thirty-three
      patients (20%) had undergone previous surgery because of endometriosis. At
      surgery, endometriosis was stage I in 50 patients (30.67%), stage II in 65
      (39.88%), stage III in 23 (14.11%), and stage IV in 25 (15.34%). Other surgical
      procedures performed with the index surgery were cystoscopy in 48 patients
      (29.45%), laparoscopic ovarian cystectomy in 24 (14.72%), laparoscopic
      hysterectomy in 15 (9.2%), laparoscopic appendectomy in 9 (5.5%), sigmoidoscopy
      in 6 (3.68%), laparoscopic oophorectomy in 6 (3.68%), extensive laparoscopic
      adhesiolysis in 5 (3.07%) bowel resection in 2 (1.25%), laparoscopic myomectomy
      in 1 (0.61%), and bladder resection in 1 (0.61%). Surgery proceeded to laparotomy
      in 6 patients (3.68%). Major surgical complications included bowel perforation,
      severe pelvic pain 1 week after laparoscopic excision, and temporary numbness of
      the right side of the perineum in 1 patient each. Minor postoperative
      complications included urinary tract infection in 3 patients and port site
      infections that resolved with oral antibiotic therapy in 2 patients. Follow-up
      was 37.82 (20.09; 34.74-40.92) months. Surgical excision of endometriosis had a
      positive effect on endometriosis-related symptoms. Four pain scores were reduced,
      with statistically significant differences (p<.001 and p<.05): dysmenorrhea,
      pelvic pain not related to menstruation, dyspareunia, and dyschezia. The positive
      effect of surgical excision on patient quality of life was demonstrated by a
      statistically significant difference on the EQ-5D index (p<.001) and the EQ-5D
      VAS (p<.001). Thirty-two (20%) patients underwent a second procedure after the
      index surgery. Endometriosis stage affects the probability of requiring further
      surgery because of recurrent symptoms. There was evidence of endometriosis at
      histologic analysis in only 13 (40.62%) patients who required further surgery.
      CONCLUSION: Laparoscopic excision of endometriosis significantly reduces pain and
      improves quality of life as measured by both the EQ-5D index and the EQ-5D VAS,
      with a low complication rate.

PMID- 20129332
TI  - Controlled clinical trial assessing the effect of laparoscopic uterine arterial
      occlusion on ovarian reserve.
AB  - STUDY OBJECTIVE: To assess the effect on ovarian reserve function after
      laparoscopic uterine artery occlusion (LUAO) compared with laparoscopic surgery
      supracervical hysterectomy (LSH) and laparoscopic myomectomy (LM). DESIGN:
      Prospective cohort study (Canadian Task Force classification II-1). SETTING:
      Hospital with experience in gynecologic minimal access surgery. PATIENTS: Ninety
      patients with uterine myomas operated on from August through December 2007.
      INTERVENTION: Ninety patients were divided into 3 groups of 30 patients each: the
      study group underwent LUAO and myomectomy (LUAO-M), control group 1 underwent
      LSH, and control group 2 underwent LM only. MEASUREMENTS AND MAIN RESULTS: Blood
      samples were collected before surgery and at 1, 3, and 6 months postoperatively.
      Concentrations of follicle-stimulating hormone (FSH), leuteinizing hormone (LH),
      and estradiol (EZ) were determined using an immunoassay, and serum inhibin B
      (INHB) concentration was evaluated using an enzyme-linked immunosorbent assay. No
      significant differences in preoperative hormone concentrations between the 3
      groups were found (p>.05). In the LSH group, FSH, LH, and E2 concentrations were
      significantly increased, whereas the INHB concentration was significantly
      decreased at 1 month postoperatively (p<.05); after 3 months, only the INHB
      concentration was significantly decreased (p<.05). However, in the LOUA-M and LM
      groups, there were no significant differences between preoperative and
      postoperative hormone concentrations (p>.05). Serum concentrations of FSH, LH,
      and INHB in the LSH group were significantly different from those in the study
      group at 1 and 3 months postoperatively (p<.05); however, the differences in
      postoperative hormone concentrations between the study group and the LM group
      were not significant (p>.05). CONCLUSION: At short-term follow-up, no significant
      effect on ovarian reserve in patients with myoma who underwent LUAO was found.

PMID- 20129333
TI  - Opportunities and risk factors for premalignant and malignant transformation of
      endometrial polyps: management strategies.
AB  - STUDY OBJECTIVE: To estimate the prevalence of benign, premalignant, and
      malignant endometrial polyps and the associated clinical risk factors for
      premalignant and malignant endometrial polyps. DESIGN: Retrospective study
      (Canadian Classification II-3). SETTING: Teaching hospital. PATIENTS: Seven
      hundred sixty-six patients with endometrial polyps. INTERVENTIONS: Hysteroscopic
      removal of endometrial polyps. MEASUREMENTS AND MAIN RESULTS: Patient clinical
      data were identified and analyzed. Frequency of premalignant and malignant
      histopathologic features in endometrial polyps was calculated. Clinical risk
      factors for premalignant and malignant endometrial polyps were analyzed.
      Endometrial polyps were histologically benign in most patients (96.21%).
      Hyperplasia with atypia in a polyp (premalignant polyp) was found in 3.26% of
      patients, and endometrial carcinoma in a polyp (malignant polyp) was detected in
      only 0.52% of patients. Independent variables that were significantly related to
      premalignant and malignant polyps (all p<.05) in a binary logistic regression
      analysis included polyp diameter (odds ratio [OR], 2.93; 95% confidence interval
      [CI], 1.191-7.20), menopause status (OR, 4.85; 95% CI, 2.09-11.27), and abnormal
      uterine bleeding (OR, 3.97; 95% CI, 1.71-9.18). CONCLUSION: Polyp diameter larger
      than 1.0cm, menopause status, and abnormal uterine bleeding may increase the risk
      of premalignant and malignant endometrial polyps.

PMID- 20129334
TI  - Hysteroscopic management of large symptomatic submucous uterine myomas.
AB  - STUDY OBJECTIVE: To evaluate the feasibility of hysteroscopic resection of large
      submucous uterine myomas. DESIGN: Prospective study (Canadian Task Force
      classification II-3). SETTING: Surgery unit of minimally invasive gynecology.
      PATIENTS: Thirty-three women with submucous myomas 5 cm or larger in diameter
      with menorrhagia, dysmenorrhea, or infertility. INTERVENTION: Hysteroscopic
      myomectomy. MEASUREMENTS AND MAIN RESULTS: Satisfaction with the surgery and an
      improvement in symptoms were the primary outcomes. Possibility of 1-step
      resection; complication rate, and disease recurrence were also considered.
      Menorrhagia was the most frequent indication (91%). According to the Wamsteker
      classification, 84.8% were type II myomas, whereas 93.9% scored 5 or higher
      according to the classification of Lasmar and colleagues. Mean operating time was
      50 minutes (interquartile range, 35-65). One-step excision was achieved in 81.8%
      of patients. Of 5 women with incomplete resection, 3 needed a second surgery, and
      2 were symptom-free. Patients with myomas larger than 5 cm or with a Lasmar score
      higher than 7 were more likely to undergo a 2-step procedure. In patients with
      myomas larger than 6 cm, recovery time was significantly longer than in those
      with smaller myomas. We recorded 3 complications: intravasation, uterine
      perforation, and postoperative anemia, in 1 patient each; at present, all 3 women
      are symptom-free. Median (range) follow-up was 10 (6-22) months. Twenty-seven
      patients (81.2%) reported they were very satisfied; 5 patients (15.2%) were
      satisfied; and 1 patient (3%) was dissatisfied. CONCLUSIONS: Hysteroscopic
      myomectomy can be the treatment of choice in symptomatic patients with a
      submucous myoma with diameter of 6 cm or less. Although this technique raises the
      possibility that complete resection may require 2 surgical sessions, it is a
      feasible surgical procedure. However, for myomas 6 cm or larger in diameter, this
      approach is less attractive. Nevertheless, we believe that all of the limiting
      criteria defined in the available literature should be evaluated individually,
      bearing in mind each patient's particular condition and the surgeon's experience
      and skill.

PMID- 20129335
TI  - Clinical and sonographic findings in suspected retained trophoblast after
      pregnancy do not predict the disorder.
AB  - STUDY OBJECTIVE: Our aim was to estimate whether there are clinical, sonographic,
      or intraoperative parameters that have good correlation with the final histologic
      study after hysteroscopic removal of suspected retained trophoblast of
      conception. DESIGN: Retrospective case control study (Canadian Classification II
      2). SETTING: A tertiary referral hospital. PATIENTS: Sixty-four patients after
      hysteroscopic removal of suspected retained pregnancy material. INTERVENTIONS: We
      divided our patients into those with true trophoblast on histologic evaluation
      (group A, n=40) and patients with other histologic findings (group B, n=24).
      Clinical parameters, as well as sonographic evidence leading to hysteroscopy were
      correlated with final pathology report. MEASUREMENTS AND MAIN RESULTS: Age,
      obstetric history, type of obstetric event, and time between primary event and
      hysteroscopy were not statistically different between the true trophoblast and
      nontrophoblast groups. Clinical signs and symptoms (fever, bleeding, and
      abdominal pain), as well as sonographic findings (size of retained mass and
      Doppler flow) were not statistically different between the 2 groups and thus
      could not predict the final disease. The only parameter correlated significantly
      to final histologic findings was the intraoperative surgeon's opinion of the
      retained material. CONCLUSIONS: Various clinical parameters, as well as
      sonographic findings including the size of the mass and Doppler test results in
      patients with suspected retained trophoblast, do not predict the final diagnosis.
      The surgeon's opinion regarding the tissue seen during hysteroscopy is the only
      parameter tested that correlates well with the final histologic evaluation. Thus
      selective removal of retained trophoblast can be performed on the basis of the
      surgeon's opinion during the procedure, whereas further potentially harmful
      interventions (curettage) can be avoided when true trophoblast is not suspected
      to minimize complications.

PMID- 20129336
TI  - Clinical evaluation of a third-generation thermal uterine balloon therapy system
      for menorrhagia coupled with curettage.
AB  - STUDY OBJECTIVES: To estimate the incidence of amenorrhea 12 months after
      treatment with a third-generation thermal uterine balloon therapy (UBT) system.
      Secondary objectives were to compare the incidence of amenorrhea observed with
      this third-generation system with that of a first-generation system, to estimate
      the effect of postprocedure curettage on patient outcome, and to evaluate the
      workings of this new system. DESIGN: Multicenter, controlled study (Canadian Task
      Force classification I). SETTING: Thirteen hospitals: 12 in the United States and
      1 in Mexico. PATIENTS: Two hundred fifty premenopausal women aged 30 years or
      older with menorrhagia not responsive to previous medical therapy for at least 3
      months. INTERVENTION: After treatment with a third-generation thermal UBT system,
      patients were randomly assigned to receive postprocedure curettage or no further
      treatment. MEASUREMENTS AND MAIN RESULTS: The rate of amenorrhea 12 months after
      treatment with the third-generation thermal UBT system was similar in patients
      receiving postprocedure curettage (33.3%) and those receiving no further
      treatment (37.1%; p=.53). In addition, postprocedure curettage did not have any
      significant effect on any other patient outcome, for example, pain. Patients who
      were matched to historic control patients treated with the original first
      generation system demonstrated a significantly greater success rate (amenorrhea)
      at 12 months (32.6%) compared with those treated with the first-generation system
      (13.7%). The third-generation thermal UBT instrument functioned as designed, with
      no unanticipated adverse device effects. CONCLUSION: The third-generation thermal
      UBT system shows greater efficacy in producing amenorrhea than the original first
      generation system, with no significant safety issues. Postprocedural curettage
      did not alter amennorhea rates.

PMID- 20129337
TI  - Laparoscopic myomectomy at 25 weeks of pregnancy: case report.
AB  - We performed laparoscopic myomectomy for treatment of a large, twisted, subserous
      myoma at 25 weeks of pregnancy in a woman with acute abdominal pain that did not
      respond to analgesic therapy. There are few reports in literature about
      laparoscopic management of uterine leiomyoma during the first half of pregnancy
      that demonstrate its feasibility in selected cases. Laparoscopic myomectomy can
      be considered a minimally invasive alternative to the traditional laparotomy when
      myomectomy is necessary during the second half of pregnancy, resulting in less
      postoperative pain and shorter recovery time.

PMID- 20129338
TI  - Retained uterine fundus after vaginal hysterectomy.
AB  - We report a case of retained uterine fundus after vaginal hysterectomy that was
      subsequently removed at laparoscopy. The patient had undergone vaginal
      hysterectomy 8 years previously and came to our hospital with abdominal pain.
      Examination revealed a supravesical mass. Laparoscopy was performed and showed
      the uterine fundus with its cornual attachments. The mass was excised and sent
      for histopathologic analysis, which confirmed that it was uterine tissue.
      Retained uterine tissue or myoma tissue has been reported, usually after
      morcellation. However, to our knowledge, our case is only the second reported
      case of retained fundus after complete vaginal hysterectomy. Because of
      adhesions, it is possible that the uterus was not completely removed. In such
      cases, laparoscopic assistance is extremely useful.

PMID- 20129339
TI  - Rare case of ovarian cystic lymphangioma.
AB  - Lymphangiomas are rare, generally benign tumors of the lymphatic system comprised
      of multiple cystic spaces lined with endothelium. Lymphangiomas may arise in any
      part of the body. Lymphangioma of the ovary is rare; we have identified only 13
      reports in a 50-year literature survey (PubMed 1959-2009). Typically,
      lymphangiomas are slow-growing tumors that remain asymptomatic for a long time.
      They are most often found incidentally in abdominal or pelvic imaging studies or
      at surgery or autopsy. Wide excision of the lesion with microscopically clear
      margins is the best approach when feasible. A postmenopausal woman had a
      symptomatic pelvic mass. Imaging studies demonstrated a complex left ovarian
      cyst. Complete removal of a cystic lymphangioma was successfully performed at
      laparoscopy. Cystic lymphangiomas should be included in the differential
      diagnosis of an ovarian cystic mass, and laparoscopic excision may be the method
      of treatment.

PMID- 20129340
TI  - Surgical management of recurrent ureteric endometriosis causing recurrent
      hypertension in a postmenopausal woman.
AB  - Endometriosis is a common condition that affects as many as 10% to 20% of women
      of reproductive age. Because of the subtle clinical signs and symptoms and
      limitations of imaging methods, the diagnosis is frequently delayed or missed,
      with serious consequences including hypertension, hydronephrosis, and loss of
      kidney function. We present an unusual case of recurrent ureteric endometriosis
      in a postmenopausal woman to highlight the challenges of screening for and
      management of endometriosis.

PMID- 20129341
TI  - Haemophilus influenzae abscess: inclusion in the differential diagnosis of a
      large pelvic mass?
AB  - BACKGROUND: This report describes an unusual first case in which an abscess
      containing Haemophilus influenzae incorporates the entire uterine cavity without
      overt signs of infection. CASE: A 39-year-old woman presented with right lower
      quadrant abdominal pain and a large abdominal pelvic mass. Evaluation with
      computed tomography and ultrasonography showed a 20- x 14- x 10-cm cystic mass
      arising from the uterus. Tumor markers were negative. The patient underwent a
      total abdominal hysterectomy. Intraoperative findings included a 20-cm
      intramyometrial uterine abscess, completely replacing the uterine cavity. The
      abscess was densely adhered to the sigmoid colon. The mass was ruptured during
      the surgical procedure when mobilizing it off the colon, and cultures were
      obtained. Microbiologic culture illustrated H. influenzae. Pathologic diagnosis
      confirmed an intramyometrial abscess, originating from the wall of the uterus
      occupying the entire uterine cavity, lined with granulation tissue, foamy
      macrophages, and chronic inflammation. CONCLUSION: Intramyometrial abscesses can
      masquerade as degenerating fibroids and, even with microorganisms, can exist
      without overt signs or symptoms of an active infection.

PMID- 20129342
TI  - Laparoscopic resection of endometriosis in a patient with a ventriculoperitoneal
      shunt using the LapDisc.
AB  - The surgical approach in a patient with a ventriculoperitoneal shunt in need of
      abdominal surgery remains controversial. The risk of increased intracranial
      pressure with pneumoperitoneum in laparoscopy is still unresolved. We used the
      LapDisc (Ethicon, Inc., Somerville, New Jersey) to access the shunt and
      temporarily seal it, which enabled us to perform laparoscopic resection of
      endometriosis without subjecting the shunt to high intraabdominal pressure. The
      benefits of this approach are the ability to perform laparoscopy, less skin-to
      shunt contact minimizing infection, and elimination of possible increased
      intracranial pressure secondary to pneumoperitoneum. With the progress made in
      the management of hydrocephalus, patients with ventriculoperitoneal (VP) shunts
      enjoy a longer lifespan. Therefore, the gynecologic laparoscopic surgeon can
      expect to treat a patient with a VP shunt in place.

PMID- 20129343
TI  - Internal herniation of adnexa through a defect of the broad ligament: case report
      and literature review.
AB  - Internal herniation through a defect of the broad ligament occurs rarely.
      Herniation of the ovary rather than the small intestine or colon is extremely
      rare. We present only the third known case of herniation of the adnexa into a
      broad ligament defect. A 42-year-old woman, gravida 3, para 2, aborta 1, had
      severe continuing right lower quadrant pain that was resistant to medical and
      surgical treatments. The clinical history was significant for long-standing
      endometriosis, 2 previous laparoscopic procedures to treat endometriosis, and
      chronic pelvic pain despite medical and surgical treatments. At the second
      laparoscopic procedure, pelvic endometriosis was excised, and a large defect of
      the right broad ligament was noted but not treated. At the third operation, right
      salpingo-oophorectomy was performed to eliminate the large broad ligament defect
      and the possibility of internal herniation on the right side as a possible
      explanation for the patient's chronic right lower quadrant pain. Postoperatively,
      the pain resolved, and the patient has been pain-free for 9 months. This type of
      internal herniation should be considered in the differential diagnosis in female
      patients with pelvic pain.

PMID- 20129344
TI  - Giant pararectal epidermoid tumor mimicking ovarian cyst: combined laparoscopic
      and perineal surgical approach.
AB  - Epidermoid cysts are benign tumors that can develop in any part of the human
      body. Pelvic cysts adjacent to the rectum develop rarely, and few cases have been
      described in the literature. We report the case of a 58-year-old woman who
      underwent laparoscopic and perineal excision of a giant pararectal cyst that was
      discovered during laparoscopy performed for preoperative provisional diagnosis of
      an adnexal mass detected on an imaging study. To our knowledge, this is the
      second case of a pararectal cyst excised using combined laparoscopic and perineal
      approaches. In the hands of skilled laparoscopic surgeons, we suggest a combined
      laparoscopic and perineal approach for excision of giant pararectal cystic tumors
      to avert laparotomy.

PMID- 20129345
TI  - Vaginal vault leiomyoma: 25 years after total abdominal hysterectomy.
AB  - Leiomyomas are benign, mesenchymal, monoclonal tumors that typically originate
      from myometrium smooth-muscle cells, although atypical sites such as the vagina,
      lungs, vascular structures, and retroperitoneal area have been reported. We
      present the case of a leiomyoma that originated from the vaginal cuff in a 70
      year-old woman, 25 years after total abdominal hysterectomy and bilateral
      salphingo-oophorectomy.

PMID- 20129346
TI  - Laparoscopic pelvic lymphadenectomy in a patient with cervical cancer stage Ib1
      complicated by a twin pregnancy.
AB  - Cervical cancer is the most frequently observed malignancy during pregnancy. The
      presence of nodal metastasis is the most important negative predictor factor, and
      its assessment is crucial in deciding whether the pregnancy can safely continue.
      To our knowledge, this is the first report of a twin pregnancy complicated by
      cancer of the uterine cervix that was successfully treated with laparoscopic
      pelvic lymphadenectomy and subsequently with neoadjuvant chemotherapy. A 35-year
      old woman, gravida 2, para 1, with a dichorionic-diamniotic twin pregnancy
      underwent laparoscopic staging of the pelvic lymph nodes at 17 weeks of
      gestation. Cervical adenocarcinoma, grade 2, stage 1b1 with lymphovascular space
      invasion was diagnosed. Nineteen negative nodes were removed, and the patient was
      counseled to continue the pregnancy. On the basis of tumor size and detection of
      lymphovascular space invasion, cisplatin as neoadjuvant chemotherapy was
      administered until week 32 of gestation, when a cesarean section delivery was
      performed, along with radical hysterectomy. No complications to the neonates or
      to the mother due to the therapy were observed. This case demonstrates the safety
      of operative nodal staging during gestation, even in a twin pregnancy. Exclusion
      of nodal metastasis may improve oncologic outcomes, and neoadjuvant chemotherapy
      should be administered when indicated.

PMID- 20129347
TI  - Diagnostic laparoscopy complicated by group A streptococcal necrotizing
      fasciitis.

PMID- 20129348
TI  - Laparoscopic approach to right diaphragmatic endometriosis with argon laser: case
      report.
AB  - Diaphragmatic involvement by an endometriotic cyst is a rare entity that may be
      responsible for chronic thoracic pain. Herein we present a case report of a 6-cm
      right diaphragmatic endometrioma treated using laparoscopic partial excision and
      argon laser coagulation of the inner cyst wall. The laparoscopic approach to
      upper abdomen endometriosis is feasible and safe when accurate evaluation of the
      case is performed.

PMID- 20129349
TI  - Laparoscopic management of placenta percreta.
AB  - The incidence of abnormal placentation is increasing as a result of the rise in
      the cesarean delivery rate. Management of placenta percreta involving the urinary
      bladder often requires extensive surgery including bladder resection. A 27-year
      old woman with placenta previa percreta that invaded the urinary bladder
      underwent delayed total laparoscopic hysterectomy performed after the portion of
      the placenta invading the bladder had regressed. This approach decreased blood
      loss associated with immediate resection and preserved the bladder intact. To our
      knowledge, this is the first report of a minimally invasive approach to placenta
      percreta involving the bladder.

PMID- 20129350
TI  - Hernias found during surgery.

PMID- 20129353
TI  - Medical treatment of cesarean scar pregnancy.

PMID- 20129354
TI  - Editorial note.

PMID- 20129355
TI  - Predictors of myocardial contractile recovery after coronary revascularization in
      patients with prior myocardial infarction.
AB  - BACKGROUND: We sought to explore the prognostic power of certain patient
      characteristics to predict myocardial contractile recovery after coronary
      revascularization in patients with prior myocardial infarction. METHODS AND
      MATERIALS: We enrolled 100 consecutive patients with prior myocardial infarction,
      significant coronary stenosis/occlusion amenable for revascularization, and
      regional wall motion abnormality in the distribution of the affected artery. All
      patients underwent echocardiographic assessment of regional wall motion and left
      ventricular ejection fraction. Patients underwent coronary revascularization by
      either percutaneous angioplasty or surgical bypass. Echocardiography was repeated
      8 weeks following revascularization. Patients were classified into two groups:
      Group 1 with evidence of contractile improvement after revascularization at
      follow-up echocardiography and Group 2 with no such evidence of improvement. The
      two groups were compared with respect to patients' clinical characteristics and
      echocardiographic and angiographic data. RESULTS: Predictors of contractile
      recovery after revascularization included angina pectoris, the shorter age of
      infarction at the time of revascularization, a higher baseline left ventricular
      ejection fraction, a lower baseline wall motion score index, the presence of
      Grade 2-3 collaterals to the infarct-related artery, and the absence of dyspnea
      or diabetes mellitus. Stepwise regression analysis identified the presence of
      Grade 2-3 collaterals to the infarct-related artery and the age of infarction at
      the time of revascularization as independent predictors of contractile recovery
      after revascularization. CONCLUSIONS: In patients with prior myocardial
      infarction, the presence of Grade 2-3 collaterals to the infarct-related artery
      and the shorter age of infarction at the time of revascularization independently
      predicted myocardial contractile recovery after coronary revascularization.

PMID- 20129356
TI  - Hyperbaric oxygen preconditioning improves myocardial function, reduces length of
      intensive care stay, and limits complications post coronary artery bypass graft
      surgery.
AB  - OBJECTIVE: The objective of this study was to determine whether preconditioning
      coronary artery disease (CAD) patients with HBO(2) prior to first-time elective
      on-pump cardiopulmonary bypass (CPB) coronary artery bypass graft surgery (CABG)
      leads to improved myocardial left ventricular stroke work (LVSW) post CABG. The
      primary end point of this study was to demonstrate that preconditioning CAD
      patients with HBO(2) prior to on-pump CPB CABG leads to a statistically
      significant (P<.05) improvement in myocardial LVSW 24 h post CABG. METHODS: This
      randomised control study consisted of 81 (control group=40; HBO(2) group=41)
      patients who had CABG using CPB. Only the HBO(2) group received HBO(2)
      preconditioning for two 30-min intervals separated 5 min apart. HBO(2) treatment
      consisted of 100% oxygen at 2.4 ATA. Pulmonary artery catheters were used to
      obtain perioperative hemodynamic measurements. All routine perioperative clinical
      outcomes were recorded. Venous blood was taken pre HBO(2), post HBO(2) (HBO(2)
      group only), and during the perioperative period for analysis of troponin T.
      RESULTS: Prior to CPB, the HBO(2) group had significantly lower pulmonary
      vascular resistance (P=.03). Post CPB, the HBO(2) group had increased stroke
      volume (P=.01) and LVSW (P=.005). Following CABG, there was a smaller rise in
      troponin T in HBO(2) group suggesting that HBO(2) preconditioning prior to CABG
      leads to less postoperative myocardial injury. Post CABG, patients in the HBO(2)
      group had an 18% (P=.05) reduction in length of stay in the intensive care unit
      (ICU). Intraoperatively, the HBO(2) group had a 57% reduction in intraoperative
      blood loss (P=.02). Postoperatively, the HBO(2) group had a reduction in blood
      loss (11.6%), blood transfusion (34%), low cardiac output syndrome (10.4%),
      inotrope use (8%), atrial fibrillation (11%), pulmonary complications (12.7%),
      and wound infections (7.6%). Patients in the HBO(2) group saved US$116.49 per ICU
      hour. CONCLUSION: This study met its primary end point and demonstrated that
      preconditioning CAD patients with HBO(2) prior to on-pump CPB CABG was capable of
      improving LVSW. Additionally, this study also showed that HBO(2) preconditioning
      prior to CABG reduced myocardial injury, intraoperative blood loss, ICU length of
      stay, postoperative complications, and saved on cost, post CABG.

PMID- 20129357
TI  - An innovative noninvasive respiratory stress test indicates significant coronary
      artery disease.
AB  - BACKGROUND: Respiratory maneuvers can uncover manifestations of myocardial
      ischemia. Some pulse wave characteristics are strongly associated with
      significant coronary artery disease (S-CAD). An innovative test using the
      respiratory stress response (RSR) has been developed for the detection of S-CAD.
      It is based on spectral analysis of finger pulse wave oscillations measured by
      photoplethysmography during deep, paced breathing at a rate of six breaths per
      minute (0.1 Hz) over 70 s. METHODS: RSR was assessed, prior to the procedure, in
      150 consecutive patients referred for coronary angiography. It was calculated by
      analyzing the relative spectral power of the respiratory peak area at 0.1 Hz,
      using proprietary software. The coronary angiograms were analyzed by quantitative
      coronary angiography by 1 cardiologist who was blinded to the RSR results. S-CAD
      was defined as luminal stenosis >70% of > or = 1 coronary artery with a diameter
      > or = 2 mm, or left main stenosis >50%. A valid RSR was obtained in 150 of 153
      patients (98%) with a mean age of 58.7 + or - 10.6 years (67% males). RESULTS: S
      CAD was found in 36 patients (24%). S-CAD patients had significantly lower RSR
      compared to patients without S-CAD (6.7% + or - 5.1 vs. 17.4% + or - 10.6;
      P<.001, respectively). Multivariate logistic regression analysis, adjusted for
      known CAD risk factors, showed that RSR is a strong independent indicator of S
      CAD (odds ratio 41.2, 95% CI 12.2-139.3; P<.001). CONCLUSION: The innovative RSR
      test is a simple, noninvasive bedside or office-based tool for the detection of S
      CAD.

PMID- 20129358
TI  - Transcatheter patent foramen ovale closure is effective in reducing migraine
      independently from specific interatrial septum anatomy and closure devices
      design.
AB  - BACKGROUND: Relationships between migraine improvement after transcatheter patent
      foramen ovale (PFO) closure and both specific interatrial septum anatomy and
      different devices design have not been investigated yet. We sought to assess
      effectiveness of transcatheter PFO closure in reducing or curing migraine with
      aura in patients with previous paradoxical embolism in relation with specific
      interatrial septum anatomy and different closure devices. METHODS AND RESULTS: We
      prospectively enrolled 34 patients (22 female and 12 male, mean age 40 + or - 3.7
      years) who were referred to our centre over a 12-month period for PFO
      transcatheter closure and migraine with aura and previous paradoxical embolism.
      All procedures were performed using mechanical intracardiac echocardiographic
      guidance. Patients were assigned to Amplatzer PFO or ASD Multifenestrated
      Occluder and Premere Occlusion System implantation dependently from intracardiac
      echocardiography anatomical findings, which included short-channel with moderate
      atrial septal aneurysm (ASA) in 6 patients (17.6 %), long-channel with moderate
      ASA in 3 patients (8.8%), short-channel with huge ASA in 5 patients (14.7%),
      multifenestrated ASA in 4 patients (11.7%), long-channel PFO without ASA in 10
      patients (29.4%), and long-channel PFO with mild ASA in 6 patients (17.6%).
      Accordingly, 18 patients received an Amplatzer Occluder (9 PFO Occluder and 7 ASD
      Multifenestrated Occluder), and 16 received a Premere Occlusion System. After a
      mean follow-up of 9.0 + or - 2.8 months, all patients improved their migraine
      symptoms (mean Migraine Disability Assessment Score 30 + or - 1.5 at baseline
      versus 6.0 + or - 2.9 in the follow up, P<.03) independently from specific
      interatrial septum anatomy and different closure devices. CONCLUSION: Although
      our study had several limitations, it suggests that independently from
      interatrial septum anatomy and device type, PFO closure in patients with migraine
      with aura resulted in a high rate of migraine improvement.

PMID- 20129359
TI  - Percutaneous coronary intervention for chronic total occlusive lesion of a left
      anterior descending artery using the retrograde approach via a septal-septal
      channel.
AB  - The retrograde approach is an effective therapeutic strategy for chronic total
      occlusion (CTO) intervention. In CTO cases, the retrograde approach from the
      opposite coronary artery is not always applicable. In certain left anterior
      descending (LAD) CTO cases, the distal LAD is filled from the septal channel
      where it is supplied by the proximal septal route. We report two LAD CTO cases of
      percutaneous coronary intervention (PCI) conducted with a wire from the proximal
      septal branch to the distal septal channel using the retrograde approach.

PMID- 20129360
TI  - Day 1 care in patients with non-ST-segment elevation myocardial infarction.
AB  - In 2007, the American College of Cardiology/American Heart Association and the
      European Society of Cardiology updated their guidelines for the management of
      patients with non-ST-segment elevation myocardial infarction (NSTEMI). Based on
      evidence from recent clinical studies, both 2007 guidelines recommend early risk
      stratification, administration of appropriate pharmacologic therapy, and
      selective use of percutaneous coronary intervention in order to reduce morbidity
      and mortality in these patients. In this article, we focus on management of
      patients with NSTEMI during the first 24 h of presentation and present a clinical
      scenario to illustrate the current guidelines-based management strategy.

PMID- 20129361
TI  - Late drug-eluting stent thrombosis: importance of intravascular ultrasound.
AB  - We report two cases of late occurring drug-eluting stent thrombosis (ST) where
      coronary angiography failed to identify the cause but intravascular ultrasound
      (IVUS) revealed underlying mechanical problems with the initial stent deployment.
      Mechanical factors such as stent underexpansion and residual edge stenoses may be
      more important in the pathogenesis of late drug-eluting ST than previously
      recognized. Intravascular ultrasound is required to reliably detect these
      problems and optimize subsequent reintervention.

PMID- 20129362
TI  - Origin of a common trunk for the inferior phrenic arteries from the right renal
      artery: a new anatomic vascular variant with clinical implications.
AB  - The inferior phrenic arteries constitute a pair of important vessels, supplying
      multiple organs including the diaphragm, adrenal glands, esophagus, stomach,
      liver, inferior vena cava, and retroperitoneum. The vast majority (80-90%) of
      inferior phrenic arteries originate as separate vessels with near equal frequency
      from either the abdominal aorta or the celiac trunk. Infrequently, the right and
      left inferior phrenic arteries can arise in the form of a common trunk from the
      aorta or from the celiac trunk. We herein present three patients with a new
      anatomic vascular variant: a common trunk of the inferior phrenic arteries
      arising from the right renal artery. In one case, the left inferior phrenic
      branch of the common trunk provided collaterals connecting with a supra
      diaphragmatic branch of the left internal mammary artery and in another with the
      lateral wall of the pericardium. Angiographic identification of a common trunk
      for the inferior phrenic arteries arising from the right renal artery is
      important for proper diagnosis and clinical management. The presence of this
      unique vascular variant can impact revascularization of the renal arteries.

PMID- 20129363
TI  - Closure of a coexisting ostium secundum atrial septal defect and patent foramen
      ovale using a single Amplatzer patent foramen ovale occluder device.
AB  - We report the case of a 59-year-old man with cryptogenic stroke who was found to
      have both an ostium secundum atrial septal defect and a patent foramen ovale
      (PFO) by intracardiac echocardiography. Both defects were successfully occluded
      using a single 35-mm Amplatzer PFO occluder device inserted through the atrial
      septal defect.

PMID- 20129364
TI  - Thrombus vaporization by excimer laser angioplasty.

PMID- 20129365
TI  - Current strategies and recent advances in the therapy of hypercholesterolemia.
AB  - Lipid therapy is an option for preventing atherosclerotic vascular disease that
      has been intensively studied and proved to be effective independent of the
      underlying risk factors. Since the optimal LDL-cholesterol appears to lie well
      below 100 mg/dl most potent lipid lowering drugs and adjunctive HDL-raising
      therapeutics are mandatory. Inhibition of cholesterol synthesis and absorption is
      currently the preferred measure. However, new developments may substantially
      increase the efficacy of lipid therapy. One is add-on colesevelam, a synthetic
      bile-acid sequestrant with increased binding affinity which allows smaller
      dosages for better tolerability. Alternatively HDL-cholesterol may be increased
      by 25% using niacin with improved tolerability due to the combination with
      laropiprant, an inhibitor of the receptor for prostaglandin D2-receptor, which
      minimizes flushing close to placebo level. Mipomersen, a specific oligonucleotide
      capable to reduce apolipoprotein B-100 up to 70%, is certainly the most advanced
      approach to challenge even apheresis as the most effective measure to lower
      exceptionally elevated cholesterol levels.

PMID- 20129366
TI  - Genetics and kinetics of familial hypercholesterolemia, with the special focus on
      FH-(Marburg) p.W556R.
AB  - OBJECTIVE: Familial hypercholesterolemia (FH) is an autosomal dominant inherited
      disorder, caused by mutations in the low density lipoprotein receptor (LDLR)
      gene. FH is characterized by elevated plasma LDL cholesterol, premature
      atherosclerosis and high risk of premature myocardial infarction. Extended work
      has been done to understand both, the primary genetic defect as well as the in
      vivo kinetic consequences of this disease. Both approaches, genetics and
      kinetics, are challenging but also fruitful approaches for a better understanding
      of this devastating disease. For this we reviewed the recent literature and used
      our in vitro and in vivo data on one of the most frequently occurring types of
      FH, the FH(Marburg) p.W556R. METHODS: To identify the primary genetic defect of
      the FH(Marburg) we used denaturing gradient gel electrophoresis (DGGE) mutation
      analysis. In vivo kinetic studies were performed in a heterozygote FH(Marburg)
      subject and in 5 healthy control subjects utilizing a stable isotope tracer
      kinetic approach with 3D-leucine. RESULTS: DGGE screening of the LDLR gene
      identified a tryptophan (W) to arginine (R) substitution at residue 556 (p.W556R)
      in the fifth conserved YWTD repeat of the LDLR-beta-propeller in FH(Marburg). In
      vivo kinetic studies in a heterozygote FH subject for FH(Marburg) and in 5
      healthy control subjects demonstrated a severe decrease in LDL FCR and a mild
      increase of LDL PR in FH compared to healthy controls. CONCLUSIONS: The LDLR
      mutation p.W556R is a frequent and severe defect for FH. This defect has a major
      influence on the in vivo lipoprotein kinetics and lipid levels. In a heterozygote
      FH patient we found a dual defect for the increase in LDL cholesterol, namely a
      decrease in the fractional catabolic rate (FCR) of LDL but also an increase in
      LDL production rate (PR). By this a well defined, single genetic defect may have
      a series of different in vivo metabolic consequences which could be used for
      potential therapeutic approaches to this disease.

PMID- 20129367
TI  - The Dresden Apheresis Center - experience with LDL apheresis and
      immunoadsorption.
AB  - The first apheresis center in former German Democratic Republic was established
      in Dresden November 1990 following the reunification of Germany. We here
      summarize the activities of this center to date. From the center's establishment
      until the end of July 2009 13,291 sessions of therapeutic apheresis have been
      performed. Four LDL apheresis methods, namely DALI, Therasorb LDL, HELP and
      lipidfiltration, are available and several comparative studies of these methods
      have been published. In addition, we have established the Therasorb IG method and
      two rheophoresis methods (Rheofilter SR 20; TheraSorb-Rheo Adsorber). Currently
      we treat 53 high-risk patients with LDL apheresis, including 6 post- heart
      transplant patients and 5 patients with immunoadsorption. Since November 1990 we
      have seen a marked reduction in the number of new cardiovascular events by
      apheresis intervention, but they could not be totally prevented and 2 patients
      died despite LDL apheresis treatment. In our clinical experience all 4 LDL
      apheresis methods appear equally effective. However, it is an advantage to have
      the ability to switch methods in patients in whom one method was less effective
      or less well tolerated. We also successfully treated patients suffering from
      Evans' syndrome, pemphigus, urticaria vasculitis with monoclonal gammopathy IgM
      Type Kappa, lichen myxoedematosus or lupus erythematodes with immunoadsorption.
      The rheophoresis approach has been used in patients with age-dependent
      degeneration of the macula, sudden hearing loss, leg ulcers, and diabetic foot
      syndrome.

PMID- 20129368
TI  - Extracorporeal LDL cholesterol elimination (25 years of experience in CZ).
AB  - In the Czech Republic the therapy of severe familial hypercholesterolemia (FH) by
      extracorporeal elimination using LDL-apheresis (immunoadsorption) and
      hemorheopheresis is concentrated into one center. The authors evaluate the long
      term therapy (3-12 years, median 7,25) in 12 patients with FH - 3 homozygous, 9
      heterozygous; Fredrickson type IIa, IIb (treated: 9 by LDL-apheresis and 3 by
      hemorheopheresis). Immunoapheretic interventions decrease LDL-cholesterol, ApoB
      and even Lp(a) by about 82 +/- 1; 73 +/- 13; 82 +/- 19 %, respectively. Selected
      non-invasive methods are important for a long-term and repeated follow-up.
      Carotid intima-media thickness showed improvement or stagnation in 75% of the
      patients. The level of some adhesive molecules, cytokines, endoglin and some
      coagulation functions were measured, but no universally accepted biomarkers
      informing of the actual activity of the disease were found to predict and plan
      the therapy. A program for procedure planning with the use of Microsoft(r) Excel
      for Windows(r) was developed. In summary, LDL-apheresis and hemorheopheresis
      substantially lower LDL-cholesterol in FH. Our experience with long-term therapy
      also shows good tolerance and a small number of complications (5,6% of clinically
      irrelevant side-effects). Hemorheopheresis may improve blood flow in
      microcirculation in familial hypercholesterolemia and also in some other
      disorders of microcirculation.

PMID- 20129369
TI  - LDL-apheresis in homozygous LDL-receptor-defective familial hypercholesterolemia:
      the Munich experience.
AB  - 23 patients, homozygotes for LDL-receptor defective familial hypercholesterolemia
      (FH), were diagnosed at our institute since 1960, eight of whom were heterozygous
      compounds. Three were lost to follow-up. Eight patients died at ages between 7
      and 60 years due to cardiovascular complications, five from acute myocardial
      infarction, one from acute left heart failure due to severe aortic stenosis, and
      two from sudden death at their home. 12 patients have been treated with regular
      LDL-apheresis, 10 of these have continued the therapy for 8 to 27 years. The
      longest treatment has lasted for 31 years and is going on. The first patient
      started with plasma exchange in 1976.

PMID- 20129370
TI  - Acute effects of lipid apheresis on human serum lipidome.
AB  - Lipid apheresis is an efficient method for reducing cholesterol and triglyceride
      serum levels, but its effect on other lipid species has not been investigated.
      This study explored the effect of LDL apheresis on the serum lipidome in
      hyperlipidemic patients with cardiovascular complications. Lipid analysis was
      performed before and immediately after a single apheresis procedure in serum
      samples of six patients treated with different apheresis methods. Conventional
      lipid parameters (TC, LDL-C, HDL-C, TG) were determined by standard enzymatic
      methods. Phosphatidylcholines (PC), sphingomyelins (SM),
      phosphatidylethanolamines (PE), PE-based plasmalogens (PE_pl),
      lysophosphatidylcholines (LPC), ceramides (Cer), free cholesterol (FC) and
      cholesterol ester (CE) were detected with electrospray ionization tandem mass
      spectrometry. LDL apheresis induced a mean reduction of LDL-C by 68% and of HDL-C
      by 14%, respectively. CE, FC, SM, and Cer revealed an apheresis-induced decrease
      of about 47%, which was not statistically different from LDL-C reduction. In
      contrast, the decline of PC (31%), LPC (26%), PE (2%), and PE_pl (37%) after
      apheresis was significantly lower in comparison to LDL-C reduction, but not
      statistically different from HDL-C decrease. While the group of PC-species
      declined uniformly during apheresis, changes in particular LPC-, Cer-, and SM
      species revealed significant differences, reflecting their differential
      distribution in lipoprotein particles and blood cells. We conclude that the acute
      effect of lipid apheresis on serum lipidome could be predominantly attributed to
      lipoprotein changes, while blood cell damages during this procedure caused
      additional, less pronounced changes. The importance of specific changes in
      particular lipid species remains to be established.

PMID- 20129371
TI  - Beyond lowering circulating LDL: apheresis-induced changes of systemic oxidative
      stress markers by four different techniques.
AB  - OBJECTIVE AND METHODS: Dyslipidemia and oxidative stress are causally related to
      atherogenesis and cardiovascular disease. We assessed acute changes of systemic
      oxidative stress biomarkers in thirty-two patients undergoing regular apheresis
      using four different techniques: heparin-induced extracorporeal LDL precipitation
      (HELP), direct adsorption of lipoproteins (DALI), lipidfiltration (LF), and
      immunoadsorption of lipoproteins (IA). RESULTS: All apheresis procedures were
      similarly effective in lowering LDL cholesterol (-2.5+/-0.2 mmoL/L), oxidized LDL
      (-52.4+/-4.4 U/L), and levels of antioxLDL antibodies (-59.5+/-15.1 U/L). Among
      the LDL-apheresis methods investigated, only the DALI technique without prior
      separation of blood plasma led to a decline in leukocyte count (p=0.01 vs. LF
      post apheresis) and to decreased phagocyte oxidant-generating activity as
      evaluated by chemiluminescence. Moreover, DALI was followed by a smaller decrease
      of blood total antioxidant capacity than the other techniques (p<0.01 vs. HELP
      post apheresis). CONCLUSION: Together, our data suggest that compared with other
      common techniques, the DALI apheresis system is accompanied by the lowest
      systemic oxidative burden evoked by a single apheresis treatment.

PMID- 20129372
TI  - Retinal vessel analysis in hypercholesterolemic patients before and after LDL
      apheresis.
AB  - OBJECTIVE: Changes in the microcirculation per se may precede macrovascular
      changes, hence, may present a good surrogate for monitoring vascular changes
      during treatment. Using retinal vascular imaging techniques, we attempted to
      investigate the microvascular benefit of a single LDL apheresis in
      hypercholesterolemia. METHODS: Twenty-one hypercholesterolemic patients (57+/-15
      years) on regular LDL apheresis treatment, seven women and 14 men, were examined
      for retinal endothelial function before and after a single LDL apheresis. The
      Dynamic Vessel Analyzer was applied for static and dynamic retinal vessel
      analysis. Retinal vessel diameter was measured at rest and during flicker light
      stimulation. Changes in vasodilation are expressed as percent changes over
      baseline. RESULTS: Cholesterol fractions and triglycerides were reduced by 21-74
      % by the LDL apheresis procedure. In hypercholesterolemic patients, flicker
      induced vasodilation was diminished in both retinal arterioles and venules, but
      had significantly improved in retinal venules after a single LDL apheresis (p =
      0.013). This increase in vasodilatory capacity of retinal venules was linked to a
      wider basal retinal venular caliber (p = 0.031), but was unrelated to changes in
      serum lipids (p > 0.05). CONCLUSION: In hypercholesterolemia, abnormal retinal
      autoregulation is improved by a single LDL apheresis. Our findings suggest that
      venules represent a dynamic component, which is highly responsive to metabolic
      changes in the microcirculation.

PMID- 20129373
TI  - A single lipid apheresis does not modulate pulse wave reflection in
      hypercholesterolemic patients.
AB  - BACKGROUND: Lipid apheresis (LA) is instituted to increase life expectancy in
      patients with previous cardiovascular events and severe and otherwise untreatable
      hypercholesterolemia. Studies have demonstrated that even a single LA markedly
      improves endothelial and micro-vascular function in patients. It is unknown
      whether these changes also impact pulse wave reflection and established
      parameters of arterial stiffness. METHODS: In 20 patients on regular LA (8
      treated by immunoadsorption, 7 by lipid filtration, 5 by direct adsorption of
      lipids) we measured peripheral blood pressure, heart rate, central systolic
      pressure (CSP), central pulse pressure (CPP), augmentation index (AIX) and pulse
      wave velocity by applanation tonometry (SphygmoCor, Atcor Medical) before and
      after a single treatment. RESULTS: Peripheral blood pressure and heart rate were
      comparable pre- and post treatment. CSP, CPP, AIX and PWV did not significantly
      change during LA independent of treatment modality although LDL-cholesterol
      levels were markedly reduced (in average from 3.5+/-0.9 to 0.9+/-0.3 mmol/L).
      CONCLUSION: The well-documented effects of a single LA on microvascular function
      are not associated with measurable changes in pulse wave reflection. Future
      studies are required in order to evaluate long-term effects of LA in this
      context.

PMID- 20129374
TI  - Severe hypertriglyceridemia: an indication for apheresis?
AB  - OBJECTIVE: Severe hypertriglyceridemia is associated with a number of severe
      complications such as acute pancreatitis. Rapid lowering of excessively elevated
      triglyceride (TG) levels is therefore a primary medical goal in these patients.
      According to previous reports, immediate apheretic treatment might be an
      interesting option in order to rapidly lower excessively elevated TG levels.
      METHODS: A review of the current available literature was therefore conducted in
      order to provide an overview of the present data on apheretic treatment for
      patients with severe hypertriglyceridemia. RESULTS: A single session of
      plasmapheresis proofs capable of lowering TG levels by up to 70%, producing clear
      clinical and laboratory improval. The best clinical benefit concerning reduction
      in morbitity and mortality can be achieved when apheresis is used as early as
      possible. Even repetitive use of apheresis is reported. There is controversy on
      technical details, such as different apheresis techniques (plasma exchange versus
      double-membrane filtration), slightly favoring plasma exchange. CONCLUSIONS: In
      patients with severe hypertriglyceridemia plasmapheresis seems to be a safe and
      useful tool in rapidly lowering excessively elevated TG levels. Apheresis can be
      used to rapidly decrease triglyceride levels, and thus remove the causative agent
      for continuing damage. The indications are medical emergencies such as
      hypertriglyceridemic pancreatitis with excessively elevated TG levels (TG > 1000
      mg/dl). If indicated, it should be used as early as possible.

PMID- 20129375
TI  - Pleiotropic effects of LDL apheresis.
AB  - LDL apheresis (LA), a technique employed to remove atherogenic lipoproteins, has
      been shown to exert a protective function on the vessel walls. This effect can be
      attributed to pleiotropic mechanisms that safeguard against endothelial
      dysfunction by reducing the concentrations of pro-inflammatory and pro
      coagulation markers. Besides these actions, LA improves whole blood viscosity and
      endothelium-mediated vasodilation, and has a positive effect on the
      hemorheological picture, improving perfusion in the microcirculation. Although
      the short term effects on the functional component of the vascular damage seem to
      be temporary, long term effects on the morphological alterations have also been
      shown. It is still not clear which of the many proposed actions, or others still
      to be discovered, is the principal vessel protective mechanism.

PMID- 20129376
TI  - Impact of LDL-apheresis on inflammation and microcirculation.
AB  - Lipid-apheresis (LIPID-A) is highly effective in reduction of pro-atherosclerotic
      LDL-cholesterol and lipoprotein (a). It has been demonstrated in prospective and
      retrospective analyses to reduce major cardiovascular events. In addition to
      improvement of pro-atherosclerotic lipoprotein milieu, LIPID-A exerts pleiotropic
      effects on inflammation and micro-circulation. Several pro-inflammatory cyto- and
      chemokines as well as adhesion molecules are cleared by distinct LIPID-A methods.
      Moreover, a single LIPID-A can induce proliferative activity of circulating
      endothelial progenitor cells and by this way, enhance vascular repair capacity.
      Microcirculation is modified by LIPID-A by influencing the balance of
      vasoconstrictory and -dilatative mediators, plasma viscosity and erythrocyte
      aggregation resulting in an activation of functional capillary reserve and blood
      flow.

PMID- 20129377
TI  - The German Lipid Apheresis Registry - remaining to be established.
AB  - BACKGROUND: The target-oriented distribution of increasingly limited health care
      resources demand data, which support the benefit of established treatment
      procedures such as lipid apheresis. In recent years, the Federal Joint Committee
      (G-BA), a paramount decision-making body of the German Health Care System,
      warrants reassessment of the approval of chronic lipid apheresis therapy for
      regular reimbursement. Therefore, in 2005, an interdisciplinary German apheresis
      working group has been established by members of both German Societies of
      Nephrology. The goal of this working group has been to revise 1.) the indication
      for lipid apheresis according to current guidelines and recommendations for the
      treatment of lipid disorders and 2.) to transfer recent advances of our
      understanding of the impact of lipoproteins for atherogenesis and thrombosis into
      these recommendations. In addition, the working group developed standardized
      report forms, which could be implemented in a software solution to establish a
      German Lipid Apheresis Registry. METHODS AND RESULTS: From 2005 to 2009 the
      working group met on a regular basis to substantiate the first defined goals. The
      indication for lipid apheresis was critically revised with respect to
      cardiovascular guidelines and actual scientific evidence and was accepted by the
      members of the apheresis working group. The first draft of report forms for the
      German Lipid Apheresis Registry was validated. Various software solutions were
      discussed, but proved not feasible because of the lack of financial sponsoring.
      CONCLUSIONS: There is consensus between the medical societies and health care
      authorities that there is a need for a German Lipid Apheresis Registry. The
      advantage of such a registry is to substantiate prospective long-term data on
      clinical outcome of chronic lipid apheresis treatment and to support additional
      clinical research activities in that field. In addition, this registry should
      comply with requests of the Federal Joint Committee (G-BA). The necessary terms
      for this registry are well defined, but financial support is an issue.

PMID- 20129378
TI  - Lipid apheresis and rheopheresis for treatment of peripheral arterial disease.
AB  - Lipid apheresis is an effective lipid-lowering treatment in drug unresponsive
      severely hypercholesterolemic patients with coronary artery disease. It results
      in symptomatic improvement, reduces progression of coronary atherosclerosis, and
      decreases coronary event rates. These effects are partly caused by aggressive
      lipid lowering itself and partly by unselective removal of high molecular weight
      proteins leading to improved hemorheology. This review summarizes current
      available data on the proposed mechanisms by which lipid apheresis acts anti
      atherosclerotic and improves ischemic symptoms. Based on this, it discusses the
      putative effects of lipid apheresis on restoring patho-physiological processes
      involved in the development of symptoms of peripheral arterial disease and
      critical limb ischemia. The available clinical experience with lipid apheresis
      and rheopheresis in treating patients with peripheral arterial disease is then
      critically reviewed and put into the context of currently available treatment
      options.

PMID- 20129379
TI  - Nitric oxide and endothelin after lipid apheresis - a pilot study.
AB  - OBJECTIVE: Patients with the heterozygous form of familial hypercholesterolemia
      (FH) display an early onset of atherosclerosis due to disturbed vascular
      endothelial function. Whether the improvements of endothelial function after
      lipid apheresis are mediated by increased NO-production or by an altered turnover
      of vasoconstrictors such as ET-1 is still unknown. This was the onset of the
      present study. METHODS: Patients with FH and advanced atherosclerosis receiving
      regular LDL apheresis at 1 to 3 weeks were recruited. Lipids, L-arginine (L-Arg),
      L-hydroxyarginine (NHA), L-citrulline as well as big endothelin (Big-ET) and
      endothelin (ET-1) were measured after DALI, HELP and TheraSorb apheresis.
      RESULTS: 17 patients with severe FH aged 55.6 years (mean) received a total of 30
      treatments. TC, LDL-C, HDL-C, TG and TC / HDL-C ratio were reduced (55, 70, 9,
      48, and 52%; p<0.01) with no differences between apheresis systems. L-Arg was
      reduced after apheresis (HELP -18.0%, DALI -26.5%; Therasorb -7.6%) and returned
      to baseline after 2 h. Big-ET (p<0.01) and ET-1 were found to be increased
      directly and 2 hours after apheresis with HELP while transiently decreasing with
      DALI and Therasorb. CONCLUSION: Improvement of endothelial function after
      apheresis seems to have multifaceted causes. The further elucidation of the
      interrelationship between endothelial dysfunction and restricted NO synthesis, as
      addressed in this study by measuring L-NHA, L-Arg, L-Cit, ET-1 and Big-ET will be
      necessary in the future.

PMID- 20129380
TI  - Familial hypercholesterolemia and lipoprotein(a) hyperlipidemia as independent
      and combined cardiovascular risk factors.
AB  - The phenotypic diversity of familial hypercholesterolemia (FH) and lipoprotein(a)
      hyperlipidemia (Lp(a)-HLP), as defined risks for coronary artery disease with
      genetic background, and their frequent co-incidence with additional
      cardiovascular risk factors require a critical revisiting of the current
      diagnostic and screening criteria as well as therapeutic recommendations
      established for FH or isolated Lp(a)-HLP, since there is no clear guidance for
      patient stratification and disease management for combined cases. Further
      evaluation of the recent biomarkers and establishment of novel biomarkers are
      necessary for extended risk assessment of cardiovascular disease in FH or Lp(a)
      HLP and to better understand the pathophysiology of these syndrome complexes.
      Lipoprotein apheresis is used as long-term treatment to reduce circulating
      lipoproteins in patients with severe FH and/or Lp(a)-HLP, particularly with
      multiple cardiovascular risks who are intolerant or insufficiently responsive to
      lipid-lowering drugs. Recent sophisticated analyses of molecular lipid species
      (lipidome) extended with transcriptomic and/or proteomic approaches may provide
      further lipid biomarkers for disease management of FH and/or Lp(a)-HLP, and
      relevant data for optimization of apheresis treatment. This review summarizes
      current studies investigating FH and Lp(a)-HLP as independent and combined
      cardiovascular risk factors, and some promising biomarker candidates for these
      entities.

PMID- 20129381
TI  - Cardiovascular events in patients with increased lipoprotein (a) - retrospective
      data analysis in an outpatient department of lipid disorders.
AB  - INTRODUCTION: The role of lipoprotein (a) (Lp(a)) in atherogenesis has been
      previously demonstrated in several trials reporting various and sometimes
      contradictory findings. Our retrospective study analyzed the incidence of
      cardiovascular events in patients with Lp(a) plasma level of more than 250 mg/l,
      which has been defined as a threshold in previous publications. METHODS: The
      files of 303 patients with Lp(a) of more than 250 mg/l were divided into 5 groups
      categorized by Lp(a) level increase and reviewed regarding age, sex, BMI,
      dyslipidemias, arterial hypertension, diabetes mellitus, family history of
      cardiovascular events, fatty liver and incidence of vascular events in
      coronaries, carotids and lower extremities. RESULTS: No significant differences
      were observed with respect to sex, age, BMI, dyslipidemias, diabetes mellitus,
      arterial hypertension and hepatic steatosis. The likely occurrence of at least
      one event was 2.77 times more in the fourth (Lp(a) 1235 +/- 82 mg/l) and 6.2
      times more in the fifth (Lp(a) 2068 +/- 471 mg/l) than in the first group (Lp(a)
      322 +/- 48 mg/l). The 5 groups differed with respect to average "events per
      patient" (p < 0.001). The magnitude of increased Lp (a) exceeded that of other
      risk factors. CONCLUSION: A substantially (more than 1100 mg/l) elevated Lp(a)
      plasma level seems to be an important predictor for the occurrence of
      cardiovascular events. It makes sense in clinical practice to consider patients
      exhibiting this elevation as having a high cardiovascular risk. In case of
      progression of atherosclerotic complications the patients should be assigned for
      lipid apheresis.

PMID- 20129382
TI  - Designing a study to evaluate the effect of apheresis in patients with elevated
      lipoprotein(a).
AB  - Lipoprotein(a) (Lp(a)) is a risk factor for premature coronary artery disease.
      Lp(a) levels can neither be influenced sufficiently by standard hypolipemic diet
      nor by drug therapy. Currently, lipid apheresis is the only option to effectively
      lower Lp(a) levels in patients with elevated Lp(a) and progressive CVD. The lipid
      clinic at the Charite University hospital Berlin and other German apheresis
      centres have longstanding positive experience with this therapeutic regimen.
      Lately, in Germany lipid apheresis was accepted as the treatment of choice for
      patients with elevated Lp(a) levels > 60 mg/dl and progressive CVD. At the same
      time, care providers were obliged to conduct a controlled trial to prove the
      efficacy of lipid apheresis for this indication. Therefore, we designed a
      prospective, randomized, controlled trial to prove the hypothesis that lipid
      apheresis decreases vascular events.

PMID- 20129383
TI  - Treatment of symptomatic HyperLp(a)lipoproteinemia with LDL-apheresis: a
      multicentre study.
AB  - LDL-apheresis (LDLa) efficacy in the treatment of symptomatic
      HyperLp(a)lipoproteinemia -HyperLp(a)- has been studied in a multicentre trial.
      After 3.1+/-2.7 years of weekly and biweekly treatment, the data from 19 patients
      (males:12; females:7; aged 53.8+/-9.3 years; mean body mass index: 24.6+/-2.3
      Kg/m2) were evaluated. Data were collected using the same questionnaire shared by
      5 participating centres. A total of 2331 procedures were performed. A mean of
      3593.7+/-800.3 ml of plasma or 8115.3+/-2150.1 ml of blood, depending upon the
      technique used (H.E.L.P., D.A.LI., Dextransulphate, Lipocollect 200), was
      regularly treated on average every 10.1+/-2.6 days. Baseline mean Lp(a) levels
      were 172.3+/-153.8 mg/dL. The mean pre-/post-apheresis Lp(a) levels decreased
      from 124.5+/-107.2 mg/dL (p<0.001 vs baseline) to 34.2+/-40.6 mg/dL (p<0.001 vs
      pre-). Baseline mean LDL-cholesterol (LDLC) levels were 152.3+/-74.6 mg/dL. The
      mean pre-/post-apheresis LDLC levels decreased from 130.4+/-61.1 mg/dL (p<0.004
      vs baseline) to 41.2+/-25.1 mg/dL (p<0.001 vs pre-). The hypolipidemic drugs
      given to the patients during LDLa were: ezetimibe+simvastatin, atorvastatin,
      rosuvastatin, pravastatin, acipimox, and omega-3 fatty acids. 58% of the patients
      had arterial hypertension. Cigarette smokers were 5.3%. Alcohol intake was
      present in 21%. 52.6% were physically active. Patients with coronary artery
      disease (CAD) submitted to coronary catheterization before LDLa were 95%. In 5.5%
      (#1) CAD recurred despite treatment with LDLa. 79% were submitted to coronary
      revascularization before LDLa. CAD was: monovasal in 8 patients (42.1%), bivasal
      in 5 (26.4%), trivasal in 4 (21%), plurivasal in 2 (10.5%). In 94.5% of the
      sample the lesions were stable (< 0% deviation) over 3.1+/-2.7 years. 37% had
      both CAD and extra-coronary artery disease. This multicentre study confirmed that
      long-term treatment with LDLa was at least able to stabilize CAD in the majority
      of the individuals with symptomatic HyperLp(a).

PMID- 20129384
TI  - Fibrinogen/LDL apheresis as successful second-line treatment of sudden hearing
      loss: a retrospective study on 217 patients.
AB  - BACKGROUND: Sudden sensorineural hearing loss (SSHL) may be caused by a reduction
      of cochlear perfusion. Cholesterol and fibrinogen negatively influence
      rheological properties of blood thus leading to alteration of microcirculation.
      Fibrinogen/LDL apheresis improves cochlear blood flow by acutely decreasing
      plasma cholesterol and fibrinogen. METHODS: Remission rates of 217 patients with
      SSHL were analysed retrospectively after single apheresis. All patients had been
      treated otherwise before without any improvement of hearing. We investigated data
      in regard to frequency of hearing loss and time between onset of symptoms and
      apheresis. RESULTS: 15% of all patients had complete remissions, whereas partial
      remissions were seen in 46%. No change of hearing threshold was seen in 33%, 2%
      worsened. Remission rates decreased from 70% for a time of 2 weeks between onset
      of SSHL and apheresis to 63% and 21% for 6 weeks and 3 months. CONCLUSION: The
      present study shows that apheresis was followed by complete or partial remissions
      in 61% of patients even as second line therapy. The window for good therapeutic
      success is approximately 6 weeks.

PMID- 20129385
TI  - Rheopheresis for sudden sensorineural hearing loss.
AB  - Patients suffering from sudden sensorineural hearing loss (SSHL), especially
      those with hearing impairment refractory to infusion therapy, need new
      therapeutic options. Fibrinogen-LDL-apheresis, covering Rheopheresis and HELP
      apheresis for the indication of SSHL, proved to be an effective treatment option
      within the therapeutic armamentarium for SSHL in two randomized controlled trials
      including each more than 200 patients, and has also been shown to be an effective
      treatment option for patients refractory to the first line standard treatment.
      Fibrinogen-LDL-apheresis effects an immediate pulsed reduction of plasma
      viscosity as well as whole blood viscosity, hypothesized to lead to a sustained
      microcirculatory recovery, thus improving the natural course of acute
      microcirculatory impairment significantly. The solid body of evidence provided by
      investigations on fibrinogen-LDL-apheresis in recent years has been recognized by
      German SSHL guidelines, proposing fibrinogen-lowering treatments like this as
      part of a multimodality approach. Superiority of fibrinogen-LDL-apheresis over
      established first line standard treatments could not been shown in general. In
      consequence, no regular reimbursement by health insurances is available, in
      particular facing the current policy of health insurances for initial therapeutic
      nihilism at the acute onset of SSHL. Patients can apply for individual
      reimbursement or must pay the cost for the treatment. Refractory patients
      hopefully will profit by growing experiences.

PMID- 20129386
TI  - Immunoadsorption in the treatment of pemphigus.
AB  - The autoimmune bullous skin disorder pemphigus is characterized by the presence
      of autoantibodies that target distinct adhesion molecules of the epidermis. The
      autoantibodies result in a loss of the epidermal adhesive properties, which in
      turn leads to the appearance of blisters and erosions on skin and mucosal
      surfaces. In the majority of cases, disease activity can be sufficiently
      controlled by systemic corticosteroids in combination with immunsuppressants, but
      pemphigus often is recalcitrant to conventional immunosuppressive therapy.
      Clinical remission can be obtained only in a minority of patients. In the past,
      only cyclophosphamide and high-dose intravenous immunoglobulin (IVIG) were
      available as second-line therapies. Meanwhile, immunoadsorption and monoclonal
      anti-CD 20 antibody rituximab have been established as further therapeutic
      options.

PMID- 20129387
TI  - Immunoadsorption for systemic lupus erythematosus.
AB  - Immunoadsorption (IAS) with various methods is used as a rescue therapy in
      severely ill SLE patients who are refractory to conventional therapeutic
      procedures. The method aims at the rapid and extensive removal of pathogenic
      immunocomplexes (IC) and (auto-) antibodies (Abs). Long-term observational
      studies suggested efficacy and have not seen an increase in the risk of
      infections (as were seen in other extracorporeal procedures). Unfortunately,
      prospective, randomized controlled trials (RCT) are lacking. Recently,
      biologicals aiming at TNF-blockade or B-cell depletion have been used to treat
      severe SLE: They are easier to apply since they do not necessitate additional
      (expensive) hardware or specially trained staff. While there is emerging evidence
      for efficacy from uncontrolled observations, no RCT could so far demonstrate
      benefit in SLE. Under these circumstances, IAS still has a role in treating
      severe SLE, when other therapies are not effective enough or are contraindicated
      (as in pregnancy). These data are reviewed and illustrated in the case of a
      pregnant lupus patient with nephrotic syndrome.

PMID- 20129388
TI  - Immunoadsorption in SLE: three different high affinity columns are adequately
      effective in removing autoantibodies and controlling disease activity.
AB  - INTRODUCTION: Pathogenic autoantibodies (Abs) are a hallmark of SLE and their
      rapid removal is beneficial in active SLE. Immunoadsorption (IAS) is effective in
      removing serum levels of all classes of immunoglobulin (Ig), immune complexes
      (IC) and anti-dsDNA Abs and appears superior to plasmapheresis with respect to
      side effects. IAS can be performed with different columns, which use different
      ligands to bind their target. In particular, high affinity columns are in the
      focus of interest. Their ligands are either sheep IgG directed against human Ig
      (Ig-column, Ig-Therasorb(r)), or staphylococcal Protein A (ProtA-column,
      Immunosorba(r)), or the synthetic peptide Gam146 (GAM-column, Globaffin(r)). In
      our experience Ig-columns have been effective in treating active renal SLE.
      However, no analysis has so far been published on which column type should be
      preferred in treating SLE patients. PATIENTS AND METHODS: Among our SLE patients
      maintained on prolonged IAS therapy, we identified those with stable renal SLE
      and low to moderate disease activity who were successfully treated by using Ig
      columns. Six of these patients were switched to ProtA-columns, keeping the rest
      of the protocol and the medication constant. In addition, two patients were
      switched from Ig- to GAM-columns. RESULTS: All types of columns significantly
      lowered the serum levels of IgG, IgM, and anti-dsDNA Abs. Disease activity was
      constantly low before and after the switch, as were parameters of renal function.
      In addition, patients with highly active disease were effectively treated when
      ProtA- (n=6) or GAM-columns (n=1) were used as first-line extracorporeal
      treatment. CONCLUSION: Our data demonstrate that all columns are adequately
      effective in controlling key parameters of SLE. Thus, it is not the type of the
      ligand, but only the outcome, i.e. the successful removal of Ig, IC, and (auto-)
      Abs that is required for controlling SLE activity.

PMID- 20129389
TI  - Immunoadsorption in the treatment of acquired haemophilia.
AB  - In acquired haemophilia (AH) healthy humans can suddenly develop severe bleeding
      due to autoantibodies (inhibitors) against clotting factors, especially factor
      VIII. The mortality rate of 21 % is considerable, and standardized treatment
      protocols have not been developed due to the low disease frequency (1-4 per
      million). Major goals of treatment are the control of bleeding events and rapid
      inhibitor elimination. Conventional treatment regimens induce immune tolerance
      via long-term immunosuppression with success rates between 52% and 82%. However,
      treatment related mortality can rise to 39%. Lack of complete remission, advanced
      age, underlying malignancies and infections related to immunosuppressive therapy
      are regarded as principal risk factors for death. The modified Bonn-Malmo
      Protocol (MBMP), an immune tolerance protocol consisting of antibody depletion
      through immunoadsorption, i.v. immunoglobulin treatment, immunosuppression and
      high dose FVIII supplementation, achieves rapid and safe control of acute
      bleeding. In the largest published single centre study of high risk patients with
      AH, we previously demonstrated that complete remission (CR) can be achieved in
      88.5% of all patients (54/61) within a median time of 3.9 wks (range: 3.2-4.5
      wks) and in 97% (54/56) of AH patients without cancer as an underlying condition.
      Those 5 patients, who suffered also from cancer, achieved partial remission (PR).
      Mortality or severe treatment-related side effects were not observed. This study
      confirmed that MBMP is a safe and effective treatment with a high curative
      potential for severe AH. However, the severity of bleeding, and therefore the
      cost-effectiveness of the approach, needs to be considered when initiating this
      treatment protocol.

PMID- 20129390
TI  - Immunoadsorption in patients with dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is characterized by ventricular enlargement and
      progressive systolic and diastolic dysfunction. Disturbances of the cellular and
      humoral immune system are frequently observed in DCM. Circulating antibodies of
      the IgG class against diverse myocardial antigens have been identified and are
      thought to play a causative role in the pathogenesis of DCM. Possible mechanisms
      include the promotion of chronic inflammation, activation of the beta1
      adrenoreceptor and activation of Fc(gamma)-receptors. Various clinical studies
      suggest a positive effect of immunoadsorption (IA) using protein A columns, with
      or without subsequent IgG substitution (IA/IgG) on symptoms, myocardial function
      and the hemodynamic situation of these patients. Decreased myocardial
      inflammation was also observed in DCM patients treated with IA/IgG. In addition
      to conservative medical treatment, IA/IgG may therefore represent a new
      therapeutic option for patients with heart failure due to DCM.

PMID- 20129391
TI  - Plasma exchange and immunoadsorption for autoimmune neurologic diseases - current
      guidelines and future perspectives.
AB  - There is increasing interest from neurologists to use therapeutic apheresis in
      autoimmune neurologic diseases due to growing knowledge of pathogenic relevance
      of autoantibodies. Developments in that field have been summarized in this review
      focusing on German guidelines and recent results from clinical research.
      Therapeutic apheresis can offer a therapeutic armamentarium with rapid response
      for severe acute neurologic symptoms, and a drug-free option for clinical courses
      being refractory to drug based strategies or complicated by drug side effects.
      Plasma exchange (PE) as the classical method has become part of current
      guidelines within basic and escalating immunomodulatory treatments of autoimmune
      neurologic diseases, and in daily practice gets increasingly replaced by
      selective immunoadsorption (IA) due to its equivalent efficacy in combination
      with a superior safety profile. Therapeutic effects of PE and IA in autoantibody
      mediated diseases can be attributed to 3 major mechanisms: immediate
      intravascular reduction of (auto-)antibody concentration, pulsed induction of
      antibody redistribution, and subsequent immunomodulatory changes. 5 treatments
      over a period of 8-10 days seem to be an appropriate regimen to restore
      neurologic function in acute flares or relapses of autoimmune neuropathies, e.g.
      myasthenic crisis, Guillain-Barre-syndrome, and steroid refractory relapse of
      multiple sclerosis. Especially in MS a better understanding is needed, who are
      the best candidates for IA.

PMID- 20129392
TI  - Specific issues in living donor kidney transplantation: ABO - incompatibility.
AB  - Pre-emptive living kidney transplantation is the best choice of therapy to treat
      patients with advanced renal insufficiency. Unfortunately in up to one third of
      all cases kidney donation was refused due to blood group incompatibility.
      Limitations in donor availability for kidney transplantation therefore require
      that ABO-incompatible transplantation is safely established. This has changed
      when a new protocol was introduced in Stockholm, Sweden, in 2001. Almost 400 ABO
      incompatible transplantations have since been performed in more than 20 centers
      with this protocol in Europe. ABO-incompatible living kidney transplantation can
      now be offered to our patients with advanced kidney disease as a safe procedure.
      To get more insight into the role ABO-incompatible organ transplantation might
      play in the near future transplantation centers currently involved in these
      processes should share their data to answer the unresolved issues we are
      concerned.

PMID- 20129393
TI  - Indication and implementation of lipidapheresis, rheopheresis, or
      immunoadsorption (lessons learnt from Germany's largest apheresis center).
AB  - Efficient modes of extracorporeal blood purification are available today for
      apheresis treatment of progressive atherosclerosis, autoimmune disease, or for
      improving hemorheology. Advanced technology and sophisticated care render
      apheresis treatment selective, safe and tolerable. Our task is to constantly
      update indications for apheresis based on best evidence available and good
      clinical practice, as well as, to determine how apheresis therapy can be made
      available to those in need or with otherwise refractory disease. Presenting
      examples of lipid apheresis, rheopheresis, or immunoadsorption for treatment of
      hypercholesterolemia, hyperlipoproteinemia (a), acute hearing loss, refractory or
      exacerbating multiple sclerosis, we highlight real world obstacles for
      implementation of treatment, resulting in still too many patients with proven or
      recommended indication left untreated. Based on the experience of the largest
      apheresis center in Germany, with more than 3,300 treatments per year, we depict
      the necessary structure for identification of patients, defining indication,
      referral, implementation of therapy, and reimbursement. Apheresis is unfamiliar
      to most patients and many practitioners or consultants. Nephrologists, performing
      >90% of apheresis treatments in Germany, have to form a network for referral
      comprising all regional care-givers, general practitioners as well as the
      respective specialists (mainly, cardiologists, endocrinologists, diabetologists,
      ORL specialists, neurologists, ophthalmologists, or rheumatologists), and
      insurances or other cost-bearing parties for offering a scientifically approved
      therapeutic regimen and comprehensive care. We have realized this concept in a
      high volume apheresis center acting in a closely knit network characterized by an
      unrelenting effort at ongoing medical education. As a consequence, we include
      approximately 10 times more patients with appropriate diagnoses in our apheresis
      program as compared to the national average.

PMID- 20129395
TI  - Enzymatic catalysis with rapid turnover-carbonic anhydrase and superoxide
      dismutase. Preface.

PMID- 20129396
TI  - Identification, bioinformatic analysis and expression profiling of candidate mRNA
      like non-coding RNAs in Sus scrofa.
AB  - Messenger RNA-like non-coding RNAs (mlncRNAs) are a newly identified group of non
      coding RNAs (ncRNAs) that may be involved in a number of critical cellular
      events. In this study, 93 candidate porcine mlncRNAs were obtained by
      computational prediction and screening, among which 72 were mapped to the porcine
      genome. Further analysis of 8 representative candidates revealed that these
      mlncRNA candidates are not highly conserved among species. Remarkably, one of the
      candidates, sTF35495, was found to be precursor of a putative porcine microRNA.
      By RACE PCR, we determined that the full length of sTF35495 was 3 kb. The protein
      coding potential of this RNA was tested in silico with no significant finding.
      Semi-quantitative RT-PCR analysis of the subgroup of 8 candidates revealed two
      distinct expression profiles and two molecules were further validated by real
      time PCR. The predicted pre-microRNA sequence in this study provides a
      potentially interesting insight into the in vivo function of porcine mlncRNAs and
      our findings suggest that they play key biological roles in Sus scrofa.

PMID- 20129397
TI  - Constructing an initial map of transmission distortion based on high density
      HapMap SNPs across the human autosomes.
AB  - Transmission distortion (TD) is a significant departure from Mendelian
      predictions of genes or chromosomes to offspring. While many biological processes
      have been implicated, there is still much to be understood about TD in humans.
      Here we present our findings from a genome-wide scan for evidence of TD using
      haplotype data of 60 trio families from the International HapMap Project.
      Fisher's exact test was applied to assess the extent of TD in 629,958 SNPs across
      the autosomes. Based on the empirical distribution of P(Fisher) and further
      permutation tests, we identified 1,205 outlier loci and 224 candidate genes with
      TD. Using the PANTHER gene ontology database, we found 19 categories of
      biological processes with an enrichment of candidate genes. In particular, the
      "protein phosphorylation" category contained the largest number of candidates in
      both HapMap samples. Further analysis uncovered an intriguing non-synonymous
      change in PPP1R12B, a gene related to protein phosphorylation, which appears to
      influence the allele transmission from male parents in the YRI (Yoruba from
      Ibadan, Nigeria) population. Our findings also indicate an ethnicity-related
      property of TD signatures in HapMap samples and provide new clues for our
      understanding of TD in humans.

PMID- 20129398
TI  - Expression and responses to dehydration and salinity stresses of V-PPase gene
      members in wheat.
AB  - Vacuolar H(+)-translocating pyrophosphatase (V-PPase) is a key enzyme related to
      plant growth as well as abiotic stress tolerance. In this work, wheat V-PPase
      genes TaVP1, TaVP2 and TaVP3 were identified. TaVP1 and TaVP2 are more similar to
      each other than to TaVP3. Their deduced polypeptide sequences preserve the
      topological structure and essential residues of V-PPases. Phylogenetic studies
      suggested that monocot plants, at least monocot grasses, have three VP paralogs.
      TaVP3 transcripts were only detected in developing seeds, and no TaVP2
      transcripts were found in germinating seeds. TaVP2 was mainly expressed in shoot
      tissues and down-regulated in leaves under dehydration. Its expression was up
      regulated in roots under high salinity. TaVP1 was relatively more ubiquitously
      and evenly expressed than TaVP2. Its expression level in roots was highest among
      the tissues examined, and was inducible by salinity stress. These results
      indicated that the V-PPase gene paralogs in wheat are differentially regulated
      spatially and in response to dehydration and salinity stresses.

PMID- 20129399
TI  - Mapping QTLs for seed yield and drought susceptibility index in soybean (Glycine
      max L.) across different environments.
AB  - Drought stress has long been a major constraint in maintaining yield stability of
      soybean (Glycine max (L.) Merr.) in rainfed ecosystems. The identification of
      consistent quantitative trait loci (QTL) involving seed yield per plant (YP) and
      drought susceptibility index (DSI) in a population across different environments
      would therefore be important in molecular marker-assisted breeding of soybean
      cultivars suitable for rainfed regions. The YP of a recombinant line population
      of 184 F(2:7:11) lines from a cross of Kefeng1 and Nannong1138-2 was studied
      under water-stressed (WS) and well-watered (WW) conditions in field (F) and
      greenhouse (G) trials, and DSI for yield was calculated in two trials. Nineteen
      QTLs associated with YP-WS and YP-WW, and 10 QTLs associated with DSI, were
      identified. Comparison of these QTL locations with previous findings showed that
      the majority of these regions control one or more traits related to yield and
      other agronomic traits. One QTL on molecular linkage group (MLG) K for YP-F, and
      two QTLs on MLG C2 for YP-G, remained constant across different water regimes.
      The regions on MLG C2 for YP-WW-F and MLG H for YP-WS-F had a pleiotropic effect
      on DSI-F, and MLG A1 for YP-WS-G had a pleiotropic effect on DSI-G. The
      identification of consistent QTLs for YP and DSI across different environments
      will significantly improve the efficiency of selecting for drought tolerance in
      soybean.

PMID- 20129400
TI  - Bivariate association analysis for quantitative traits using generalized
      estimation equation.
AB  - Quantitative traits often underlie risk for complex diseases. Many studies
      collect multiple correlated quantitative phenotypes and perform univariate
      analyses on each of them respectively. However, this strategy may not be powerful
      and has limitations to detect pleiotropic genes that may underlie correlated
      quantitative traits. In addition, testing multiple traits individually will
      exacerbate perplexing problem of multiple testing. In this study, generalized
      estimating equation 2 (GEE2) is applied to association mapping of two correlated
      quantitative traits. We suppose that a quantitative trait locus is located in a
      chromosome region that exerts pleiotropic effects on multiple quantitative
      traits. In that region, multiple SNPs are genotyped. Genotypes of these SNPs and
      the two quantitative traits affected by a causal SNP were simulated under various
      parameter values: residual correlation coefficient between two traits, causal SNP
      heritability, minor allele frequency of the causal SNP, extent of linkage
      disequilibrium with the causal SNP, and the test sample size. By power analytical
      analyses, it is showed that the bivariate method is generally more powerful than
      the univariate method. This method is robust and yields false-positive rates
      close to the pre-set nominal significance level. Our real data analyses attested
      to the usefulness of the method.

PMID- 20129401
TI  - Risk, regulation and the growing marginalisation of CAM.

PMID- 20129402
TI  - Outcomes of traditional Chinese medicine (traditional acupuncture) treatment for
      people with long-term conditions.
AB  - A set of outcome questionnaires has been developed to measure the range of
      treatment effects of traditional acupuncture. In this descriptive outcome study
      we validated these questionnaires in a busy National Health Service funded
      acupuncture clinic serving communities of diverse socio-economic circumstances.
      Some of the questionnaires performed better than others in this setting but EQ-5D
      and MYMOP-qual both showed statistically and clinically significant improvement
      in physical and psychological health after six weeks and six months, in all
      categories of disease and degrees of chronicity. Both the written qualitative
      data and the Patient Enablement Instrument (PEI) demonstrated considerable
      patient enablement and, for some patients, the acquisition of new coping and self
      care strategies.The questionnaires were feasible to administer, acceptable to
      patients and clinic staff, and provided robust and detailed quantitative and
      qualitative outcome data of use for service provision, future planning, and as a
      basis for further cost-effectiveness studies.

PMID- 20129403
TI  - The uses and properties of almond oil.
AB  - Almond oil [Oleum amygdalae] has long been used in complementary medicine circles
      for its numerous health benefits. Although no conclusive scientific data exists
      currently, almonds and almond oil have many properties including anti
      inflammatory, immunity-boosting and anti-hepatotoxicity effects. Further,
      associations between almond oil and improved bowel transit have been made, which
      consequently reduces irritable bowel syndrome symptoms. Further, some studies
      show a reduced incidence of colonic cancer. Moreover, cardiovascular benefits
      have also been identified with almond oil elevating the levels of so-called 'good
      cholesterol', high-density lipoproteins (HDL), whilst it reduces low-density
      lipoproteins (LDL). Historically, almond oil had been used in Ancient Chinese,
      Ayurvedic and Greco-Persian schools of Medicine to treat dry skin conditions such
      as psoriasis and eczema. Further, it is through anecdotal evidence and clinical
      experiences that almond oil seemingly reduces hypertrophic scarring post
      operatively, smoothes and rejuvenates skin. Almond oil has emollient and
      sclerosant properties and, therefore, has been used to improve complexion and
      skin tone. Further studies looking into the use of almond oil post-operatively
      for the reduction of scarring are suggested.

PMID- 20129404
TI  - Cortisol as a marker for improvement in mindfulness-based stress reduction.
AB  - While much attention has been devoted to examining the beneficial effects of
      Mindfulness-Based Stress Reduction programs on patients' ability to cope with
      various chronic medical conditions, most studies have relied on self-report
      measures of improvement. Given that these measures may not accurately reflect
      physiological conditions, there is a need for an objective marker of improvement
      in research evaluating the beneficial effects of stress management programs.
      Cortisol is the major stress hormone in the human organism and as such is a
      promising candidate measure in the study of the effects of Mindfulness-Based
      Stress Reduction programs. In conjunction with other biological measures, the use
      of cortisol levels as a physiological marker of stress may be useful to validate
      self-reported benefits attributed to this program. In the current manuscript, we
      review the available literature on the role of cortisol as a physiological marker
      for improvement with regards to mindfulness practice, and make recommendations
      for future study designs.

PMID- 20129405
TI  - Balancing act: women and the study of complementary and alternative medicine.
AB  - While research indicates that women compose the majority of users and
      practitioners of complementary and alternative medicine, very little is known
      about their experiences as students of CAM. The following article draws upon
      ethnographic research conducted at a multidisciplinary institution of CAM
      education in the United States, which emphasizes an integrated model of medicine,
      collaboration with allopathic practitioners, and science-based curricula as part
      of the project of professionalization. Focusing on the first year of a Master of
      Science in Acupuncture and Oriental Medicine program, I explore women's
      motivations for pursuing training in CAM; their experiences of learning; and
      their visions of future practice. Although female students conceive of themselves
      as pioneers in the field, they also feel constrained by family and relationship
      obligations, suggesting that there may be female-specific challenges of learning,
      and ultimately practicing, complementary medicine.

PMID- 20129406
TI  - Correspondence of the auricular acupoint with the upper trapezius muscle: a
      electromyographic study.
AB  - Presently, acupuncture is a technique considered to be capable of stimulating the
      regulatory systems of the organism, such as the central nervous system, the
      endocrine system and the immunological system. The median frequency of the upper
      trapezium muscle with 40% and 60% of maximal voluntary contraction (MVC) of 15
      healthy volunteers, was analyzed after the individuals were submitted to the AA
      treatment. The non-parametric Friedman test was used to compare median frequency
      values. In this exploratory study, the level of significance of each comparison
      was set to p<0.05. The intraclass analyses indicate a significant increase of the
      median frequency muscle at 60% of the MVC (Wicoxon test). Based on the results
      found, the AA peripheral stimulus can act as a modulator mechanism of muscle
      activity and was possible to verify correspondence of the auricular acupoint with
      the trapezius muscle.

PMID- 20129407
TI  - Evaluating a complementary therapies clinic: outcomes and relationships.
AB  - BACKGROUND: There are few published examples of research examining the effect of
      massage, aromatherapy, and reflexology in clinic settings. In addition to
      measuring treatment outcomes, it may also be important to measure the quality of
      the relationship between the client and therapist and assess its contribution to
      outcomes. AIMS: To evaluate perceived changes in client quality of life following
      treatment; to determine whether the relationship between the client and therapist
      predicts the outcome of treatment; to assess the usefulness of the measures used.
      METHOD: The Measure Yourself Medical Outcome Profile (MYMOP2) and the Working
      Alliance Inventory (WAI) were used to collect data from 66 clients and 13
      therapists in a complementary therapies clinic in South Wales. RESULTS: The
      MYMOP2 data showed significant improvements for client symptoms and activity but
      not for well-being. A low correlation was found between MYMOP2 profile scores and
      WAI scores suggesting that symptoms, activity and well-being were associated with
      a positive working alliance but this narrowly failed to achieve statistical
      significance. CONCLUSION: Further research is necessary to confirm improvements
      in client quality of life and to establish causes. More research is needed to
      examine the client-therapist relationship and treatment outcome.

PMID- 20129408
TI  - Measurement of quality of life and participant experience with the mindfulness
      based stress reduction program.
AB  - Clinical studies of MBSR have reported efficacy in treating pain, mood disorders,
      arthritis, sleep disturbances, and stress. Several academic medical institutions
      in the United States offer MBSR to their patients, but it has never been offered
      at Mayo Clinic. The objective of this study was to collect quality-of-life data
      from subjects who participated in the first MBSR program offered at Mayo Clinic.
      The class was taught as a collaborative effort with the University of Minnesota
      that had an established MBSR program. Sixteen participants completed a validated,
      12-question, linear analogue self-assessment instrument, administered at the
      beginning and end of the program. Comparison of assessment scores using paired t
      tests showed statistically significant improvement in overall quality of life
      (P=0.04), mental well-being (P=0.005), physical well-being (P<0.001), emotional
      well-being (P<0.001), level of social activity (P=.02), and spiritual well-being
      (P=0.006). Although positive changes also were observed for frequency of pain,
      severity of pain, level of fatigue, level of support from friends and family, and
      financial and legal concerns, they were not statistically significant. A short
      intervention in the education of mindfulness significantly improved quality of
      life for participants.

PMID- 20129409
TI  - A pilot study of the effectiveness of reflexology in treating idiopathic
      constipation in women.
AB  - OBJECTIVES: Constipation is a common problem in the UK, affecting up to 20% of
      the population. Reflexologists claim that reflexology can be beneficial in the
      treatment of constipation. The aim of this exploratory pilot study was to
      determine the effectiveness of reflexology in treating idiopathic constipation in
      women and it is the first study of the effectiveness of reflexology for the
      treatment of women with idiopathic constipation defined according to Rome II
      criteria. METHODS: Nineteen female patients referred to a specialist biofeedback
      service with idiopathic constipation defined by Rome II criteria were recruited.
      A course of reflexology treatment (weekly for six weeks) was given. Patients'
      subjective perception of constipation was recorded as well as the Hospital
      Anxiety and Depression Scale (HAD), the Short form 36 (SF36), whole gut transit
      and the Holistic Complementary and Alternative Medicine Questionnaire (HCAMQ)
      before and after the intervention. RESULTS: All participants completed the
      intervention and none were lost to follow-up. Ninety-four percent of participants
      identified their constipation to be improved to some extent. Ten participants had
      improved colonic transit times and two patients had normalised colonic transit.
      Ten patients (53%, p=0.19) demonstrated an improved anxiety score and 11
      participants (58%, p=0.14) demonstrated an improved depression score on the HAD
      scales. Improvement was seen in general health, mental health and vitality on the
      SF36 scale, with vitality improving significantly (p<0.05). Sixty-three percent
      of participants had a more positive attitude (p=0.03) towards CAM and holistic
      health following treatment. CONCLUSIONS: This study shows that in this sample
      reflexology has potential benefit for treating idiopathic constipation in women.
      Further randomised trials are required.

PMID- 20129410
TI  - Children's experiences of their participation in a training and support programme
      involving massage.
AB  - This study reports on a research project that aimed to extrapolate the value of
      the Training and Support Programme (TSP), involving massage, among children with
      cerebral palsy (CP). Data gathering included information from interviews with a
      sub-sample of children and the TSP therapist observation forms. Data were
      analysed using standard thematic content analysis to identify key themes and
      issues of importance to children. Results showed that children enjoyed the
      relaxing aspects of massage and reported a number of improvements in their health
      such as improved muscle relaxation, mobility and bowel movements, and reduced
      pain. Future studies may need to explore other ways of extrapolating data from
      this population and similar populations where communication is impaired due to
      disability, but at the same time ensure that their views are listened to and
      acted upon.

PMID- 20129411
TI  - A literature review of complementary and alternative medicine use by colorectal
      cancer patients.
AB  - This paper sought to review the literature on complementary and alternative
      medicine (CAM) use by patients with colorectal cancer (CRC). METHODS: A
      systematic search of Pubmed and Embase was conducted to identify the relevant
      literature. Study investigators reviewed the titles of identified articles and
      one abstracted data from the eligible studies. Of the 39 English and French
      citations screened, 4 observational studies were included. RESULTS: Up to 75% of
      CRC patients reported using at least one CAM. The bio-based and mind-body
      therapies were the most commonly used. Nearly half of the studies showed that
      patients used CAM to improve general health and well-being. CONCLUSIONS: Future
      research may focus on how CAM use affects quality of life over time and in
      relation to changing health states, cancer stage and treatment to enable health
      care professionals to better inform CRC patients of the CAMs that may be helpful
      at particular points during the disease and treatment trajectories.

PMID- 20129412
TI  - Together and apart: collegiality and individuality in research centres.

PMID- 20129413
TI  - Incorporation of multiwalled carbon nanotubes to acrylic based bone cements:
      effects on mechanical and thermal properties.
AB  - Polymethyl methacrylate (PMMA) bone cement-multiwalled carbon nanotube (MWCNT)
      nanocomposites with a weight loading of 0.1% were prepared using 3 different
      methods of MWCNT incorporation. The mechanical and thermal properties of the
      resultant nanocomposite cements were characterised in accordance with the
      international standard for acrylic resin cements. The mechanical properties of
      the resultant nanocomposite cements were influenced by the type of MWCNT and
      method of incorporation used. The exothermic polymerisation reaction for the PMMA
      bone cement was significantly reduced when thermally conductive functionalised
      MWCNTs were added. This reduction in exotherm translated in a decrease in thermal
      necrosis index value of the respective nanocomposite cements, which potentially
      could reduce the hyperthermia experienced in vivo. The morphology and degree of
      dispersion of the MWCNTs in the PMMA matrix at different scales were analysed
      using scanning electron microscopy. Improvements in mechanical properties were
      attributed to the MWCNTs arresting/retarding crack propagation through the cement
      by providing a bridging effect into the wake of the crack, normal to the
      direction of crack growth. MWCNT agglomerations were evident within the cement
      microstructure, the degree of these agglomerations was dependent on the method
      used to incorporate the MWCNTs into the cement.

PMID- 20129414
TI  - The mechanical response of the ovine lumbar anulus fibrosus to uniaxial, biaxial
      and shear loads.
AB  - Analytical and computational models of the intervertebral disc (IVD) are commonly
      employed to enhance understanding of the biomechanics of the human spine and
      spinal motion segments. The accuracy of these models in predicting physiological
      behaviour of the spine is intrinsically reliant on the accuracy of the material
      constitutive representations employed to represent the spinal tissues. There is a
      paucity of detailed mechanical data describing the material response of the
      reinforced-ground matrix in the anulus fibrosus of the IVD. In the present study,
      the 'reinforced-ground matrix' was defined as the matrix with the collagen fibres
      embedded but not actively bearing axial load, thus incorporating the contribution
      of the fibre-fibre and fibre-matrix interactions. To determine mechanical
      parameters for the anulus ground matrix, mechanical tests were carried out on
      specimens of ovine anulus, under unconfined uniaxial compression, simple shear
      and biaxial compression. Test specimens of ovine anulus fibrosus were obtained
      with an adjacent layer of vertebral bone/cartilage on the superior and inferior
      specimen surface. Specimen geometry was such that there were no continuous
      collagen fibres coupling the two endplates. Samples were subdivided according to
      disc region - anterior, lateral and posterior - to determine the regional
      inhomogeneity in the anulus mechanical response. Specimens were loaded at a
      strain rate sufficient to avoid fluid outflow from the tissue and typical stress
      strain responses under the initial load application and under repeated loading
      were determined for each of the three loading types. The response of the anulus
      tissue to the initial and repeated load cycles was significantly different for
      all load types, except biaxial compression in the anterior anulus. Since the
      maximum applied strain exceeded the damage strain for the tissue, experimental
      results for repeated loading reflected the mechanical ability of the tissue to
      carry load, subsequent to the initiation of damage. To our knowledge, this is the
      first study to provide experimental data describing the response of the
      'reinforced-ground matrix' to biaxial compression. Additionally, it is novel in
      defining a study objective to determine the regionally inhomogeneous response of
      the 'reinforced-ground matrix' under an extensive range of loading conditions
      suitable for mechanical characterisation of the tissue. The results presented
      facilitate the development of more detailed and comprehensive constitutive
      descriptions for the large strain nonlinear elastic or hyperelastic response of
      the anulus ground matrix.

PMID- 20129415
TI  - Mechanical properties of brain tissue by indentation: interregional variation.
AB  - Although many studies on the mechanical properties of brain tissue exist, some
      controversy concerning the possible differences in mechanical properties of white
      and gray matter tissues remains. Indentation experiments are conducted on white
      and gray matter tissues of various regions of the cerebrum and on tissue from the
      thalamus and the midbrain to study interregional differences. An advantage of
      indentation, when compared to standard rheological tests as often used for the
      characterization of brain tissue, is that it is a local test, requiring only a
      small volume of tissue to be homogeneous. Indentation tests are performed at
      different speeds and the force relaxation after a step indent is measured as
      well. White matter tissue is found to be stiffer than gray matter and to show
      more variation in response between different samples which is consistent with
      structural differences between white matter and gray matter. In addition to
      differences between white matter and gray matter, also different regions of brain
      tissue are compared.

PMID- 20129416
TI  - On modelling and analysis of healthy and pathological human mitral valves: two
      case studies.
AB  - Biomechanical data and related constitutive modelling of the mitral apparatus
      served as a basis for finite element analyses to better understand the physiology
      of mitral valves in health and disease. Human anterior and posterior leaflets and
      chordae tendinae from an elderly heart showing no disease and a hypertrophic
      obstructive cardiomyopathic heart (HOCM) were mechanically tested by means of
      uniaxial cyclic extension tests under quasi-static conditions. Experimental data
      for the leaflets and the chordae tendinae showed highly nonlinear mechanical
      behaviours and the leaflets were anisotropic. The mitral valve from the HOCM
      heart exhibited a significantly softer behaviour than the valve from the healthy
      one. A comparison with porcine data was included because many previous mitral
      modelling studies have been based on porcine data. Some differences in mechanical
      response were observed. Material parameters for hyperelastic, transversely
      isotropic constitutive laws were determined. The experimental data and the
      related model parameters were used in two finite element studies to investigate
      the effects of the material properties on the mitral valve response during
      systole. The analyses showed that during systole the mitral valve from the HOCM
      heart bulged into the left atrium by taking on the shape of a balloon, whereas
      the anterior leaflet of the healthy valve remained in the left ventricle.

PMID- 20129417
TI  - Development of wear resistant NFSS-HA novel biocomposites and study of their
      tribological properties for orthopaedic applications.
AB  - Implants made of nickel free austenitic stainless steel can reduce the toxic
      effect of released nickel ion and compounds from the conventional stainless
      steels. On the other hand, hydroxyapatite is a ceramic which has been used in
      orthopaedic applications due to its good osteoconductivity, biocompatibility and
      bioactivity. However, there is no evidence in the literature up to now on
      producing composites based on nickel free stainless steel and hydroxyapatite and
      study of their tribology. The aim of this work was to produce novel biocomposites
      made up of nickel free stainless steel with hydroxyapatite (prepared by heat
      treating bone ash) and studying their tribology under various loads in air and in
      Ringer's physiological solution. Different amounts of hydroxyapatite powder (10,
      20, 30 and 40% Vol.) were added to this nickel free stainless steel powder to get
      the biocomposites. Variation of their density, hardness, wear resistance and
      friction with the ceramic (hydroxyapatite) content and wear load were
      investigated in air and in Ringer's solution. The density of the composites was
      decreased by increasing the volume percentage of the hydroxyapatite, while wear
      resistance of the composites was increased. The wear mechanism of these
      composites was changed by increasing the wear load and consequently the volume
      loss was enhanced dramatically. Furthermore, by increasing the sliding distance,
      the rate of volume loss was decreased slightly. The friction coefficient of the
      composites was also decreased by increasing the weight percentage of
      hydroxyapatite. Effect of the physiological Ringer's solution on wear resistance
      and friction coefficient of the composites was nearly negligible. The wear
      mechanisms of the samples were identified by studying the SEM images of the worn
      surfaces of the tested samples in different wear loads and HA contents.

PMID- 20129418
TI  - Characterization of indentation response and stiffness reduction of bone using a
      continuum damage model.
AB  - Indentation tests can be used to characterize the mechanical properties of bone
      at small load/length scales offering the possibility of utilizing very small test
      specimens, which can be excised using minimally-invasive procedures. In addition,
      the need for mechanical property data from bone may be a requirement for
      fundamental multi-scale experiments, changes in nano- and micro-mechanical
      properties (e.g., as affected by changes in bone mineral density) due to drug
      therapies, and/or the development of computational models. Load vs. indentation
      depth data, however, is more complex than those obtained from typical macro-scale
      experiments, primarily due to the mixed state of stress, and thus interpretation
      of the data and extraction of mechanical properties is more challenging. Previous
      studies have shown that cortical bone exhibits a visco-elastic response combined
      with permanent deformation during indentation tests, and that the load vs.
      indentation depth response can be simulated using a visco-elastic/plastic
      material model. The model successfully captures the loading and creep
      displacement behavior, however, it does not adequately reproduce the unloading
      response near the end of the unloading cycle, where a pronounced decrease in
      contact stiffness is observed. It is proposed that the stiffness reduction
      observed in bone results from an increase in damage; therefore, a plastic-damage
      model was investigated and shown capable of simulating a typical bone indentation
      response through an axisymmetric finite element simulation. The plastic-damage
      model was able to reproduce the full indentation response, especially the reduced
      stiffness behavior exhibited during the latter stages of unloading. The results
      suggest that the plastic-damage model is suitable for describing the complex
      indentation response of bone and may provide further insight into the
      relationship between model parameters and mechanical/physical properties.

PMID- 20129419
TI  - Thermal behavior and mechanical properties of physically crosslinked PVA/Gelatin
      hydrogels.
AB  - Poly (vinyl alcohol)/Gelatin hydrogels are under active investigation as
      potential vascular cell culture biomaterials, tissue models and vascular
      implants. The PVA/Gelatin hydrogels are physically crosslinked by the freeze-thaw
      technique, which is followed by a coagulation bath treatment. In this study, the
      thermal behavior of the gels was examined by differential scanning calorimetry
      (DSC) and dynamic mechanical thermal analysis (DMTA). Rheological measurement and
      uniaxial tensile tests revealed key mechanical properties. The role of polymer
      fraction in relation to these mechanical properties is explored. Gelatin has no
      significant effect on the thermal behavior of PVA, which indicates that no
      substantial change occurs in the PVA crystallite due to the presence of gelatin.
      The glass transition temperature, melting temperature, degree of crystallinity,
      polymer fraction, storage modulus (G') and ultimate strength of one freeze-thaw
      cycle (1FT) hydrogels are inferior to those of 3FT hydrogels. With coagulation,
      both 1FT and 3FT hydrogels shifted to a lower value of T(g), melting temperature
      and polymer fraction are further increased and the degree of crystallinity is
      depressed. The mechanical properties of 1FT, but not 3FT, were strengthened with
      coagulation treatment. This study gives a detailed investigation of the
      microstructure formation of PVA/Gelatin hydrogel in each stage of physical
      treatments which helps us to explain the role of physical treatments in tuning
      their physical properties for biomechanical applications.

PMID- 20129420
TI  - Elastomechanical properties of bovine veins.
AB  - Veins have historically been discussed in qualitative, relative terms: "more
      compliant" than arteries, subject to "lower pressures". The structural and
      compositional differences between arteries and veins are directly related to the
      different functions of these vessels. Veins are often used as grafts to reroute
      flow from atherosclerotic arteries, and venous elasticity plays a role in the
      development of conditions such as varicose veins and valvular insufficiency. It
      is therefore of clinical interest to determine the elastomechanical properties of
      veins. In the current study, both tensile and vibration testing are used to
      obtain elastic moduli of bovine veins. Representative stress-strain data are
      shown, and the mechanical and failure properties reported. Nonlinear and
      viscoelastic behavior is observed, though most properties show little strain rate
      dependence. These data suggest parameters for constitutive modeling of veins and
      may inform the design and testing of prosthetic venous valves as well as vein
      grafts.

PMID- 20129421
TI  - Effect of light-curing method on wear and hardness of composite resin.
AB  - The primary aims of this study is to determine the wear and microhardness of
      composite resin cured with a light emitting diode (LED) and to make a comparison
      with a conventional halogen light curing unit (VLC LCU). The effect of load on
      weight loss was also investigated. For the wear tests, composite specimens were
      prepared in a rectangular mold. Specimens were divided into 5 groups; the first
      three groups were polymerized with LED LCU for 10, 20, and 40 s. Groups 4 and 5
      were polymerized with VLC LCU for 20 and 40 s. Each group was divided into 2
      subgroups according to the wearing loads (60 N and 90 N). Weight loss was
      recorded using a conventional Tribometer (mg). Specimens cured using LED showed
      greater hardness and less wear compared to conventional VLC-cured specimens under
      comparable test conditions. The improved wear resistance of LED-cured material
      demonstrated here for the first time-suggests significant advantages for clinical
      practice.

PMID- 20129422
TI  - Detection of dentinal cracks using contrast-enhanced micro-computed tomography.
AB  - A new technique using contrast enhanced micro-computed tomography (micro-CT) was
      developed to improve the ability to detect dentinal cracks in teeth and assess
      associated risks to oral health. Extracted, whole human molars that exhibited
      visual evidence of external cracks following extraction and machined, partially
      fractured elephant dentin specimens were labeled by BaSO(4) precipitation and
      imaged by micro-CT. Contrast-enhanced micro-CT was demonstrated in vitro to
      enable non-destructive, 3-D imaging of the presence, morphology and spatial
      location of dentinal cracks in whole human molars and machined specimens. BaSO(4)
      staining provided enhanced contrast for the detection of cracks that could not be
      detected prior to staining. Backscattered SEM micrographs showed that BaSO(4) was
      precipitated on the surfaces of dentinal cracks and within adjacent tubules. The
      new methods demonstrated in this study are expected to be useful for clinical and
      scientific studies investigating the etiology and treatment of dentinal cracks in
      teeth.

PMID- 20129423
TI  - Fatal carbamazepine induced fulminant eosinophilic (hypersensitivity)
      myocarditis: emphasis on anatomical and histological characteristics, mechanisms
      and genetics of drug hypersensitivity and differential diagnosis.
AB  - The most severe adverse reactions to carbamazepine have been observed in the
      haemopoietic system, the liver and the cardiovascular system. A frequently fatal,
      although exceptionally rare side effect of carbamazepine is necrotizing
      eosinophilic (hypersensitivity) myocarditis. We report a case of hypersensitivity
      myocarditis secondary to administration of carbamazepine. Acute hypersensitivity
      myocarditis was not suspected clinically, and the diagnosis was made post-mortem.
      Histology revealed diffuse infiltration of the myocardium by eosinophils and
      lymphocytes with myocyte damage. Clinically, death was due to cardiogenic shock.
      To best of our knowledge this is the second case of fatal carbamazepine induced
      myocarditis reported in English literature.

PMID- 20129424
TI  - A half century retrospective study of homicide-suicide in Geneva--Switzerland:
      1956-2005.
AB  - This study provides a retrospective review from the forensic files of the
      University Centre of Legal Medicine in Western Switzerland in Geneva, from
      January 1956 to December 2005. The studied homicide-suicide cases cover a period
      of half a century (50 years). As a rule, all police-ordered forensic examinations
      of violent death cases in the Canton of Geneva are conducted by the University
      Centre of Legal Medicine. All of the data necessary for an exhaustive
      retrospective study are thus readily available. During the period covered in this
      work, 228 homicides were perpetrated in Geneva. In 23 cases, the homicide was
      followed by the suicide of the aggressor. The 34 victims of these homicides (18
      women, 1 man and 15 children) had either an intimate or filial relationship with
      the perpetrator. Most of the suicidal perpetrators were men that killed their
      spouses or intimate partners, with children as additional victims in some cases.
      Shooting was the most common means to kill, followed by stabbing. The majority of
      the victims and perpetrators were Swiss nationals. This retrospective study shows
      that in the last 50 years, homicide-suicide cases in the Canton of Geneva have
      been a rare and an episodic phenomena with a very variable frequency from 1 year
      to another.

PMID- 20129425
TI  - Applications and limitations of Forensic Biomechanics: a Bayesian perspective.
AB  - Forensic Biomechanics is an analytic method intended for presentation in a court
      of law. The method consists of the reconstruction of an injury mechanism followed
      by a comparison between the injury risk of the mechanism and the injury tolerance
      of the individual. In recent years some courts have excluded such testimony
      based, in part, on the inability of experts to quantify the potential error of
      the methods they relied upon in reaching their conclusions. The application of
      Bayes' Law to a forensic test of truth in a disputed matter allows for
      quantification of the error inherent in the method through the conditioning of
      the pre-test probability of the test outcome with the true and false positive
      rate of the test. The result of the calculation is the Error Odds (O(E)) for the
      test, or the ratio of correct to incorrect tests. We present an Error Odds
      analysis of seven previously published case studies in Forensic Biomechanics as
      an illustration of the utility of the O(E) as a metric for admissibility of
      testimony in the courts, with a minimum Error Odds ratio of 10 proposed as a
      threshold. The results of our analysis yielded only 1 of 7 cases of applied
      Forensic Biomechanics that surpassed the threshold for admissible testimony of
      10, with most the cases falling below an O(E) of 3. The results of the present
      study suggest that the forensic application of biomechanics is potentially
      fraught with error. We suggest that an Error Odds analysis be incorporated in
      Forensic Biomechanics as part of the analysis as a form of quality control and as
      demonstrable evidence of the accuracy of the methodology.

PMID- 20129426
TI  - Study of the normal internal organ weights in Tehran's population.
AB  - OBJECTIVE: Examine the normal adult internal organ weight and its relationship
      with body height, body weight, body mass index and age. MATERIALS AND METHODS:
      Prospective analysis of data from 1222 autopsies in Legal Medicine Organization
      of Iran from 1st January, 2007 to 1st September, 2008. All the subjects were
      adult residents of Tehran died from external causes and showed no pathological
      changes. RESULTS: The weight of the brain, heart, lungs, liver, spleen, pancreas,
      kidneys, thyroid gland, the pituitary gland, the suprarenal glands, testes,
      prostate, ovaries and the uterus were collected from 914 males and 308 females
      between 15 and 88 years. The weight of all the organs was correlated
      statistically with at least one external parameter with the exception of the
      pancreas in men, the uterus, the spleen and the thyroid in women. Organ weights
      decreased with age except for the heart and the prostate, and increased in
      relation to body height and/or BMI. Except for the brain, the organ weight showed
      a better statistical correlation with the BMI than the body height. CONCLUSION:
      These results can be used as standard organ weights to determine abnormal
      evidences in Forensic and Pathologic corpses. However such results have to be
      regularly updated by pathologists in order to keep organ weight as a good
      criterion used in postmortem diagnosis.

PMID- 20129427
TI  - Sex differences from fingerprint ridge density in the Indian population.
AB  - Determination of individuality is one of the prime concerns in forensic
      investigation. The study of fingerprints is widely used in providing a clue
      regarding identity. The present study was undertaken to study the sex differences
      in fingerprint ridge density in the Indian population. The study done on 100
      males and 100 females revealed that significant sex differences occur in the
      fingerprint ridge density. The present study shows a statistically significant
      difference in fingerprint ridge densities of male and female fingerprints in
      people of Indian origin. A mean fingerprint ridge density of 12 ridges/25 mm(2)
      or less is found to be more likely to be of males and a mean ridge count of more
      the 12 ridges/25 mm(2) is more likely to be of female origin.

PMID- 20129428
TI  - Resuscitation and conjunctival petechial hemorrhages.
AB  - In recent years, cardiopulmonary resuscitation (CPR) has been discussed as a
      cause of petechial hemorrhage in eyelids and conjunctivae, which could be of
      substantial significance to forensic expertises in cases of suspected
      strangulation. In the reported series or case observations, the combination of
      CPR and petechiae seemed to be sufficient to explain such a causal connection.
      Nearly all presented cases were victims for which the mechanisms resulting in
      death were themselves well-known causes explaining the development of such
      petechiae; and said mechanisms can frequently be observed in victims that did not
      receive CPR. An earlier, also retrospective, analysis of a series of forensic
      autopsies did not confirm CPR as a significant cause of conjunctival petechiae.
      Now we present the result of a prospective examination of 196 resuscitations of
      adult patients with separate assessment of petechiae being present even prior to
      resuscitation. Petechiae were present in 12 cases - but in eight of them prior to
      resuscitation already. Three other persons with petechiae found only after CPR
      were in the group of successfully resuscitated persons and exhibited petechiae
      hours after CPR during therapy in intensive care units - during a phase of
      ongoing cardiac insufficiency, which obviously caused them. The only case with
      petechiae observed neither immediately prior to nor after unsuccessful
      resuscitation, but during a follow-up examination one day later, needs to be
      discussed. It is not interpreted as reliable evidence for the causality of CPR
      though. Our interpretation of reports in literature as well as our experiences
      confirm the absence of actual proof of petechiae being generated by CPR and in
      the presence of generally significant doubts of this relation.

PMID- 20129429
TI  - Y-chromosomal STR haplotype diversity in males from Santa Catarina, Brazil.
AB  - One-hundred and nine unrelated and healthy males from Santa Catarina, Brazil were
      included in this study. Allele frequencies and gene diversities for the loci
      DYS456, DYS458 and DYS448 were calculated. A comparison between our population
      and others was performed.

PMID- 20129430
TI  - Chlamydia trachomatis infection in children: do not forget perinatal acquisition:
      a case report of a 7-year old girl, C. trachomatis infected, presumed sexually
      assaulted.
AB  - A 7-year old girl suspected of having been sexually abused owing to the presence
      of anal condyloma was found to be infected by Chlamydia trachomatis.
      Microbiological analysis and anamnesis were consistent with the infection having
      been acquired at birth. This case confirms that untreated infection acquired at
      birth can persist for months or years and highlights the value of examining those
      involved in the suspicion of sexual abuse of the child.

PMID- 20129431
TI  - Chronic hepatitis C--assessment in civil law: a case study.
AB  - This article describes the case of a 58-year-old man who asked for an assessment
      of physical damage of a civil nature, having been diagnosed with chronic
      hepatitis C for which he blamed a blood transfusion, supposedly contaminated with
      hepatitis C virus (HCV). After studying the documentary information, a number of
      presuppositions were drawn up with a view to determining the causal nexus, but
      this could not be proved. The assessment of situations like this is not common in
      civil law. This article is intended to add to the body of information on the
      forensic assessment of similar cases.

PMID- 20129432
TI  - Death by attack from a domestic buffalo.
AB  - Attacks on humans by domestic animals causing fatal injuries are not uncommon in
      rural areas of India. But injuries due to buffalo gore are rarely observed in
      villages and are different from other casualties like stab injuries, road
      fatalities, etc. As the victims of buffalo attack are usually recovered from the
      fields or forest, the investigating officer could be mislead as to the nature of
      infliction of fatal injuries to a possible homicide. The injuries caused by the
      horns of buffaloes are of various shapes, sizes and directions. They are violent
      and goring in nature. The wound sustained may be contusions, lacerations, criss
      cross wounds, penetration of body cavities, and sometimes fractures. In the
      absence of any eye witness, it becomes very difficult to believe the unsuspecting
      domestic water buffalo as attacker. This case is reported for its rarity, for the
      awareness of the possible injuries in such unnatural deaths, and factors
      predisposing to a buffalo attack.

PMID- 20129433
TI  - Contribution of teeth in human forensic identification--discriminant function
      sexing odontometrical techniques in Portuguese population.
AB  - We investigate the accuracy of odontometric methods in sex determination, using a
      sample from the Portuguese population. Measurements were made on dental casts
      using a digital caliper, and various odontometric indexes have been defined using
      upper incisor and canine teeth. Comparison of the means in both sexes was
      performed using Student's t-test. Significant differences (p<0.05) were found in
      all variables except for the "Incisor Index". The canine showed the greatest
      sexual discriminant characteristics. In the presence of one or both canines the
      distobuccal-mesiolingual crown diameter and the "Robustness Value" allowed
      discrimination between sexes in the studied population. We also provide further
      arguments on the debate on whether sex determination is population specific.

PMID- 20129434
TI  - Paraphilias and sexual offences in the Bible.

PMID- 20129435
TI  - How much do Hong Kong emergency physicians know about common legal situations?

PMID- 20129436
TI  - Emergency care--more than just a collection of tasks.

PMID- 20129437
TI  - Research plan for developing trauma core competencies for nurses in Thailand.
AB  - The aim of this research plan was identification and development of core
      competencies for emergency trauma nurses in Thailand. The research plan was
      undertaken in three phases. Phase I: a national survey of the critical dimensions
      of care; Phase II: development of a 64 item tool; and Phase III: efficiency study
      with emergency nurses representing Level-1, Regional, Community and Rural
      facilities. Six dimensions of competency were identified: cooperation, decision
      making, leadership, problem-solving, teamwork, and technical knowledge with a
      content validity index (CVI) of 1.00 and internal consistency (Cronbach's alpha)
      of 0.98 (N=485 RNs in 29 hospitals). Analysis of the first year pilot study data
      using a 5 point likert scale (N=285 RNs in 16 hospitals), nurses rated themselves
      as 4.18 (SD=0.69) and their peers at 4.00 (SD=0.68). Head nurse evaluations
      averaged 3.98 (SD=0.55). ANOVA demonstrated no statistical significance (p=0.09)
      between groups. The results of the preliminary studies demonstrated
      appropriateness of the core competency items, but refinement is required prior to
      national distribution.

PMID- 20129438
TI  - Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and
      prognostication: a scientific statement from the International Liaison Committee
      on Resuscitation; the American Heart Association Emergency Cardiovascular Care
      Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on
      Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical
      Cardiology; the Council on Stroke (Part II).
AB  - AIM OF THE REVIEW: To review the epidemiology, pathophysiology, treatment and
      prognostication in relation to the post-cardiac arrest syndrome. METHODS:
      Relevant articles were identified using PubMed, EMBASE and an American Heart
      Association EndNote master resuscitation reference library, supplemented by hand
      searches of key papers. Writing groups comprising international experts were
      assigned to each section. Drafts of the document were circulated to all authors
      for comment and amendment. RESULTS: The 4 key components of post-cardiac arrest
      syndrome were identified as (1) post-cardiac arrest brain injury, (2) post
      cardiac arrest myocardial dysfunction, (3) systemic ischaemia/reperfusion
      response, and (4) persistent precipitating pathology. CONCLUSIONS: A growing body
      of knowledge suggests that the individual components of the post-cardiac arrest
      syndrome are potentially treatable.

PMID- 20129439
TI  - An examination of emergency department nurses' attitudes towards deliberate self
      harm in an Irish teaching hospital.
AB  - PURPOSE: The purpose of this study was to examine emergency department (ED)
      nurses' attitudes towards individuals presenting with deliberate self-harm (DSH),
      including the relationship between attitudes and factors such as age, academic
      achievements, length of experience, and self-harm education. METHOD: The study
      adopted a quantitative descriptive and correlational design. ED nurses'
      attitudes, working in a level 1 trauma ED in the Republic of Ireland, were
      surveyed, using an amended version of McAllister's et al. [McAllister, M.,
      Creedy, D., Moyle, W., Farrugia, C., 2002. Nurses' attitudes towards clients who
      self-harm. Journal of Advanced Nursing 40(5), 578-586.] Attitude Towards
      Deliberate Self-Harm Questionnaire (ADSHQ). The survey yielded an 85% (n=68)
      response rate. RESULTS: The study found that ED nurses held positive attitudes
      towards individuals presenting with DSH. No correlation was found between total
      scores and gender, ED experience, or a history of self-harm education, although
      older nurses and hospital trained nurses had less positive attitudes. Age and
      length of clinical experience produced a trend in which attitudes increased,
      reached a peak and then declined. CONCLUSION: Although ED nurses in this study
      hold positive attitudes, ongoing continuing education, which was identified as a
      key theme in the study, remains an important strategy to maintain and further
      improve attitudes. The need for research into aspects of care such as knowledge,
      awareness and empathy is recommended, as is the need to evaluate the extent to
      which the National Strategy for Suicide Prevention 2005-2014 recommendations
      [Department of Health and Children, Health Service Executive, National Suicide
      Review Group 2005. Reach Out - Irish National Strategy for Action on Suicide
      Prevention 2005-2014. <http://www.nosp.ie/reach_out.pdf> (accessed 22.02.08)]
      have been implemented.

PMID- 20129440
TI  - Patient experience of the triage encounter in a Swedish emergency department.
AB  - Emergency department triage is a prerequisite for the rapid identification of
      critically ill patients and for allocation of the correct acuity level which is
      pivotal for medical safety. The patient's first encounter with a medical
      professional in the emergency department is often with the triage nurse.
      OBJECTIVES: To identify patient experience of the triage encounter. METHODS: A
      questionnaire focusing on the patient-triage nurse relationship in terms of
      satisfaction with the medical and administrative information, privacy and
      confidentiality in the triage area as well as triage nurse competence and
      attitude was answered by 146 participating patients. RESULTS: The majority of
      patients perceived that while they were triaged immediately upon arrival to the
      emergency department, they were often given limited information about the waiting
      time. Although almost a quarter of the patients did not wish to have information
      about their medical condition from the triage nurse, 97% of the patients
      considered the triage nurse to be medically competent for the triage task.
      CONCLUSIONS: Patients were generally satisfied with the reception and care given
      by the triage nurses, but less satisfied about information about expected waiting
      time. We suggest therefore, that patients should be routinely informed about
      their estimated waiting time to be seen by the doctor in addition to their triage
      level.

PMID- 20129441
TI  - Pride and prejudice: PV bleeding in same sex pregnancy.

PMID- 20129442
TI  - Thoracic and neck trauma. Part one.
AB  - This is the first of a four part series discussing thoracic trauma. Part one
      discusses the anatomy and physiology of the thorax, assessment and initial
      nursing interventions, imaging and adjuncts to diagnosis. Part 2 describes
      specific chest wall and lung injuries, types of pneumothoraces and their
      diagnosis and management. Section 3 examined other types of thoracic injuries and
      their management, such as trauma to the diaphragm and heart. The final part
      provides a brief but concise overview of neck anatomy, trauma and management.

PMID- 20129443
TI  - Setting new standards--emergency care in the 21st Century.

PMID- 20129444
TI  - [Improving long-term graft survival by limiting nephrotoxicity of
      immunosuppressors and reducing vascular risk].

PMID- 20129445
TI  - [Weaning from corticosteroid therapy after kidney transplantation].
AB  - For years, the numerous side effects of long term steroid administration have
      motivated their elimination from the immunosuppressive regimen in renal
      transplantation. However until the 90's, steroid withdrawal induced an increase
      in the incidence of acute rejection episodes, and some studies described a
      significant risk of graft loss. New immunosuppressive drugs (tacrolimus,
      mycophenolate and mTOR inhibitors) have led to reevaluate steroid
      discontinuation. Recent trials with these drugs have shown that late steroid
      withdrawal (3 months post-transplant) was no more associated with a higher risk
      of acute rejection or graft loss. Some studies have demonstrated an improvement
      in the cardiovascular risk factors and a decreased incidence of infections and
      osteoporosis. Its positive impact on patient survival remains to be confirmed in
      long term follow-up studies.

PMID- 20129446
TI  - [Transplantation without corticosteroids].
AB  - Used in kidney transplantation to prevent and treat rejection, corticosteroids
      induce a number of adverse side effects over the long term. With the arrival of
      new immunosuppressive drugs, trials on rapid corticosteroid interruption, a few
      days or weeks after transplantation, and transplantation without corticosteroids
      other than the intraoperative bolus, have been conducted in patients at low
      immunological risk and on particular patient profiles such as children and Afro
      Americans. These studies show that early cessation of corticosteroids, whether in
      these two categories of patients or in patients at low immunological risk, make
      it possible to reduce the adverse side effects with no harmful influence on
      patient or graft survival or renal function. The increase in the rejection rate
      observed with this procedure has no consequences over the medium term after
      treatment. However, for full success, this strategy must absolutely be carried
      out under the cover of an induction and an immunosuppressive bitherapy. In these
      conditions, early interruption of corticosteroids also has beneficial effects
      over the longer term: it encourages the reduction in the frequency and/or
      severity of diabetes, weight gain, hypertension, or dyslipidemia and seems to
      better preserve patients'bone status.

PMID- 20129447
TI  - [Nephrotoxicity of calcineurin inhibitors: presentation, diagnostic problems and
      risk factors].
AB  - Nephrotoxicity of calcineurin inhibitors (CNIs) is an acute, reversible and
      chronic, irreversible pathology. Histologically, acute nephrotoxicity manifests
      as hemodynamic modifications caused by vasoconstriction of the essentially
      afferent arterioles resulting in a drop in the glomerular filtration rate.
      Chronic nephrotoxicity is characterized by arteriolar hyalinosis resulting in a
      variety of tubulointerstitial and glomerular lesions with an essentially ischemic
      mechanism. However, these histological lesions, whether chronic or acute, are not
      specific of CNI toxicity and can be seen in the course of many pathological
      circumstances in kidney transplantation. This absence of specificity makes the
      histological diagnosis of CNI nephrotoxicity difficult. In addition, the
      individual risk of developing CNI nephrotoxicity, difficult to predict based
      solely on the pharmacokinetic parameters of systemic CNI exposure, also involves
      local exposure (CNI concentrations in the graft) modulated by several, notably
      pharmacogenetic factors. The difficulty of diagnosing CNI nephrotoxicity and the
      interindividual variability of its risk require development of new diagnostic
      tools so that the patients at highest risk of developing severe CNI
      nephrotoxicity lesions, in whom minimization protocols would produce the best
      risk-benefit ratio, can be identified.

PMID- 20129448
TI  - [Review of clinical trials on minimization and interruption of calcineurin
      inhibitors (CNIs) and protocols without CNIs in the transplantation of different
      organs (kidney, heart, and liver)].
AB  - Immunosuppressive therapy with calcineurin inhibitors (CNI) must be continued
      during the weeks following transplant to avoid acute rejection. Over the long
      term, however, nephrotoxicity and morbidity induced by CNIs have a negative
      impact on patient and transplant survival. Therefore, for any organ, it is
      crucial to free patients from the nephrotoxicity associated with CNIs without
      risking under-immunosuppression and while maintaining good overall tolerance. For
      kidney transplants, minimization of CNI use in association with mycophenolate
      seems to be relatively safe and allows for improved kidney function without an
      added risk of rejection. The strategy of making a complete switch from CNIs to
      proliferation signal inhibitors (PSI) also seems to be promising. In patients
      with chronic allotransplant dysfunction, reduction of CNI doses by 30 to 50% in
      association with MPA seems to be safe and effective and replacement of CNIs with
      PSIs is pertinent, though limited by their effect on proteinuria. For liver
      transplants, late and minimal introduction of CNIs under induction seems to be
      safe and effective for the preservation of kidney function, especially when
      precarious. For heart transplants, preliminary studies conducted on a small
      number of patients suggest that delayed introduction of CNIs at minimal doses and
      late elimination of the therapy are safe after transplant.

PMID- 20129449
TI  - [Benefits of proliferation signal inhibitors beyond immunosuppression. Vascular
      protection and experience in heart transplantation].
AB  - Proliferation Signal inhibitors (PSI), sirolimus and everolimus, possess
      immunosuppressive and antiproliferative properties that have a substantial impact
      in organ transplantation. Their antiproliferative and pro-apoptotic action on
      vascular smooth muscle cells and endothelial cells, with positive effects on
      vascular remodeling, intimal proliferation, and atheroma plaques, has been
      demonstrated in many experimental studies in cell culture and on animal vascular,
      cardiac, and renal models. In humans, the PSI show a major advantage in heart
      transplantation, since they contribute satisfactory immunosuppression while
      preventing coronary vasculopathy related to intimal proliferation of smooth
      muscle cells, a factor that limits the long-term success of the graft.
      Intravascular ultrasound explorations, which measure intima thickness, showed
      that PIS treatment can inhibit intracoronary intimal proliferation after heart
      transplantation and thus reduce the morbidity and mortality at the medium term in
      transplantation patients. In kidney transplantation, even though their impact is
      less clear for the moment because of the multifactorial aspect of chronic graft
      dysfunction, the PSI nevertheless contribute undeniable benefits in terms of
      improving renal function and reducing the histological lesions of chronic
      allograft nephropathy.

PMID- 20129450
TI  - [Proliferation signal inhibitors: what therapeutic protocols are followed in
      2009?].
AB  - Proliferation signal inhibitors (PSI) have been used in France for kidney
      transplants for some ten years. They provide a certain number of long-term
      benefits for kidney function in transplant patients due to their anti
      proliferation and anti-tumour properties and absence of nephrotoxicity. Their use
      has been evaluated in therapeutic regimens aimed at reducing the nephrotoxicity
      associated with calcineurin inhibitors (CNI). Strategies based on minimizing the
      use of CNIs and therapy switches between 3 and 6 months have shown promising
      results, especially in terms of prevention of deterioration of kidney function.
      The best time to make the switch has not yet been defined with certainty, but
      predictors of success, preservation of good kidney function and absence of
      proteinuria have been established. Aside from cases of demonstrated CNI toxicity,
      a history or onset of de novo cancer is a situation in which this type of regimen
      can be considered.

PMID- 20129451
TI  - [The use of mTOR inhibitors in kidney transplantation: who are the best patients
      and how should these inhibitors be used?].
AB  - The choice of immunosuppression treatment in the kidney transplant patient
      depends on many factors: a history of cutaneous tumor; immunological, vascular,
      and primary cytomegalovirus infection risks; delay in the graft resuming
      function; patient knowledge of the side effects of immunosuppressant treatments,
      etc. Starting from a case study, this article describes the indications and
      contraindications of mTOR inhibitor use in the long-term immunosuppression
      strategy in the kidney transplantation patient. It also discusses the delay after
      grafting when the mTOR inhibitors can be introduced, immediately or at a later
      time, and points out some advantages of mycophenolate or calcineurin inhibitor
      substitution with mTOR inhibitors.

PMID- 20129452
TI  - [Replacing calcineurin inhibitors with proliferation signal inhibitors after
      kidney transplantation: indications, results, and disadvantages].
AB  - In the kidney transplant patient, calcineurin inhibitor (CNI) treatment is a
      major risk factor for chronic allograft nephropathy (CAN). Immunosuppressive
      strategies based on non-nephrotoxic drugs such as proliferation signal inhibitors
      (PSIs) have been conceived to reduce or even interrupt CNIs. CNI conversion, with
      progressive cessation over 3 months with a PSI can significantly improve renal
      function, notably if the patient presents proteinuria less than 0.8 g/day and if
      conversion is undertaken early, when the glomerular filtration rate (GFR) is 40
      ml/min or greater. In these conditions GRF improvement is associated with a
      histological CADI score and chronic lesion markers. Nevertheless, replacing CNIs
      with a PSI can occasionally induce proteinuria that is potentially related to
      direct toxicity of the PSI on the podocytes, which must be monitored to prevent
      recurrence of nephrotoxicity lesions.

PMID- 20129453
TI  - [The new drugs in development for kidney transplantation].
AB  - Several drugs currently under development may have uses in transplantation,
      whether they are developed directly in this domain or in others such as clinical
      immunology. The transplantation community has greatest hope in three new organic
      compounds currently in phase II trials. ISA247, a cyclosporine analog, has the
      advantage of inducing less posttransplantation diabetes and CP-690550, a specific
      inhibitor of the JAK3 protein kinase, has an effect comparable to tacrolimus on
      the acute rejection rate and kidney function. As for AEB071, a protein kinase C
      inhibitor, it should find its place in association with everolimus in the
      minimization of anticalcineurin doses. Two biological agents in phase II/III of
      development are also expected: belatacept, a CTLA4-Ig fusion protein that has
      already demonstrated efficacy comparable to cyclosporine while maintaining better
      renal function, and alefacept, an LFA3-IgG1 fusion protein whose efficacy and
      tolerance assessment are currently underway. Other drugs such as the B anti
      lymphocytes, currently being developed in other indications, could be tested in
      transplantation, given the involvement of humoral immunity.

PMID- 20129454
TI  - [Debate concerning the optimal blockage of the renin-angiotensin system].

PMID- 20129455
TI  - [The renin-angiotensin system in hypertension and in cardiovascular and renal
      diseases: highlights of the World Congress of Nephrology 2009]].

PMID- 20129456
TI  - Genetic data of twelve X-STRs in a Japanese immigrant population resident in
      Brazil.
AB  - In the last years, several works have been published on the variability of X
      markers; however, few were on Asian populations. In this work, we present the
      genetic data of 12 X-STRs (DXS9895, DXS7132, DXS6800, DXS9898, DXS6789, DXS7133,
      GATA172D05, DXS7130, HPRTB, GATA31E08, DXS7423, DXS10011) obtained from a sample
      of 232 individuals of Japanese origin residing in Brazil. Most markers
      investigated present a high genetic diversity, with the exception of DXS6800. No
      deviations from Hardy-Weinberg equilibrium were observed, with the exception of
      DXS7133 locus. Linkage disequilibrium analysis did not reveal consistent evidence
      of association between the X-STRs used. The comparison of the Japanese immigrant
      population with other Asian populations (Japanese, Chinese, and Korean)
      demonstrates the inexistence of significant allelic frequency differences between
      these populations in most systems investigated.

PMID- 20129457
TI  - Haplotype diversity of 17 Y-chromosomal STR loci in the Bangladeshi population.
AB  - Haplotype and allele frequencies of 17 Y-chromosomal STR loci were determined in
      216 unrelated Bangladeshi males. AmpFlSTR Y-filer PCR Amplification kit (Applied
      Biosystems) was used to type the following Y-STR markers: DYS19, DYS389I,
      DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS438, DYS439, DYS437,
      DYS448, DYS458, DYS456, DYS635, and Y-GATA-H4. A total of 211 haplotypes for the
      17 Y-STR markers were detected and, of these, 206 haplotypes were unique. The
      haplotype diversity was 0.9998, indicating a high potential for differentiating
      between male individuals in this population. Comparison analysis via Analysis of
      Molecular Variance (AMOVA) and construction of Neighbor Joining Tree revealed a
      close association of Bangladeshi population with Indian Gaddi and Southern Indian
      populations.

PMID- 20129458
TI  - Allele frequencies of 15 STRs in a representative sample of the Brazilian
      population.
AB  - Allele frequencies for 15 short tandem repeat (STR) loci were obtained from a
      sample of 12,030 individuals undergoing paternity testing. This sample includes
      individuals from all States in Brazil, combined according to the current country
      division into five regions (North, Northeast, Central West, Southeast, and
      South). The most polymorphic loci were D2S1338 and D18S51. All the analysed loci
      meet Hardy-Weinberg equilibrium expectations. Combined power of discrimination
      and combined power of exclusion for the 15 tested STR loci were 0.999999999999990
      and 0.9999992, respectively. Comparative analysis between populations from
      different Brazilian macroregions as well as between Brazil and other relevant
      populations are presented.

PMID- 20129459
TI  - Allele frequencies for the four major sub-populations of New Zealand for the 15
      Identifiler loci.
AB  - Allele frequencies for the 15 STRs included in the AmpFlSTR Identifiler (Applied
      Biosystems Incorporated, Foster City, CA, USA) STR DNA profiling system have been
      determined for the four major sub-populations of New Zealand. The data set is
      comprised of DNA profiles obtained over a 12-year period and includes profiles
      obtained using the Second Generation Multiplex (SGM, Forensic Science Services,
      UK), and the AmpFlSTR SGMPlus (Applied Biosystems Incorporated, Foster City, CA,
      USA) STR DNA profiling systems.

PMID- 20129460
TI  - Genetic polymorphism of 11 Y-chromosomal STR loci in Yunnan Han Chinese.
AB  - Allele frequencies and haplotypes of 11 Y-chromosome STR loci, DYS19, DYS389I,
      DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385 ab, DYS438, DYS439 and DYS437
      were determined in 320 unrelated Yunnan Han Chinese males. A total of 293
      haplotypes were identified, of which 268 were unique, 23 were shared in two
      individuals, and 2 were shared in three individuals. The allele diversity values
      for each locus ranged from 0.4087 (DYS438) to 0.9701 (DYS385). The allele
      observed haplotypes diversity value was 0.9994. The combined Y-chromosome STR
      polymorphisms provide a powerful discrimination tool for routine forensic
      applications.

PMID- 20129461
TI  - The hare and the tortoise: one small step for four SNPs, one giant leap for SNP
      kind.
AB  - A recently published study has used next-gen sequencing technology to resequence
      two Y chromosomes separated by 13 generations and discovered four single-base
      differences in approximately 10Mb DNA, suggesting that the Y chromosome
      euchromatin accumulates around one mutation per generation. Y-SNPs therefore now
      offer the best resolution of Y haplotypes and promise to distinguish almost every
      Y chromosome. This work illustrates the promise of current sequencing technology
      for forensically relevant applications.

PMID- 20129462
TI  - Secondary DNA transfer of biological substances under varying test conditions.
AB  - This research investigates factors that may influence the secondary transfer of
      DNA. These include the type of biological substance deposited, the nature of the
      primary and secondary substrate, moisture content of the deposit and type of
      contact between the surfaces. Results showed that secondary transfer is
      significantly affected by both the type of primary substrate and the moisture
      (wetness) of the biological sample. Porous substrates and/or dry samples
      diminished transfer (with on average only 0.36% of biological material being
      transferred from one site to another), whereas non-porous substrates and/or wet
      samples facilitated transfer events (approximately 50-95% of biological material
      was transferred from one site to another). Further, the type of secondary
      substrate also influenced transfer rate, with porous surfaces, absorbing
      transferred biological substances more readily than non-porous ones. No
      significant differences were observed among the biological substances tested
      (pure DNA, blood and saliva). Friction contact between the two substrates
      significantly enhanced secondary transfer compared to either passive or pressure
      contact. These preliminary results will assist in developing general assumptions
      when estimating probability of a secondary DNA transfer event under simple
      conditions.

PMID- 20129463
TI  - Genetic profiles and sex identification of found-dead wolves determined by the
      use of an 11-loci PCR multiplex.
AB  - A previously described canine-specific 9-STR multiplex, now including two markers
      for sex determination, was tested for the genotyping of 23 wolves from Northern
      and Central Portugal. The samples were collected at necropsies and presented
      varying states of preservation. Complete profiles were obtained in 74% of the
      samples, partial profiles in 22% and one completely null profile. This survey
      revealed 15 alleles not previously described in dogs, distributed among 6 STR
      loci. It is shown that this genotyping system, previously tested in domestic
      dogs, can be reliably used for obtaining complete genetic profiles in wolves with
      a matching probability of 2.45 x 10(-9) and compatible sex identification, even
      in sub-optimal samples. Moreover, a population structure analysis using the
      observed genotypes revealed that this multiplexed 11-loci panel may potentially
      be used for discriminating between wolves and dogs.

PMID- 20129464
TI  - A forensic method for the simultaneous analysis of biallelic markers identifying
      Y chromosome haplogroups inferred as having originated in Asia and the Japanese
      archipelago.
AB  - Information regarding the ancestral and geographical origins of biological
      evidence samples may be useful for crime investigators as they narrow down the
      possible donors of the sample. A method for simultaneous analysis of seven
      biallelic markers (M130, M131, M57, M125, M175, M122 and M134) was developed for
      forensic application. M57, M125 and M131 are included to identify haplogroups
      inferred as having originated in the Japanese archipelago. Our method employs
      allele-specific PCR and fragment analysis using fluorescently labeled primers and
      capillary electrophoresis. This method can be used to assign a haplogroup from
      both of degraded male DNA samples and DNA samples containing a mixture of female
      and male DNA by designing PCR primers that generate small amplicons and are
      highly specific for targets on the Y chromosome. A total of 1346 samples from
      Japanese males collected from the four major islands and Okinawa island were
      classified into seven Y binary haplogroups i.e., C-M130, C-M131, D-M57, D-M125, O
      M175, O-M122 and O-M134, and a "no-mutation detected" group and their frequencies
      were 0.0617, 0.0565, 0.1441, 0.182, 0.3418, 0.11, 0.0847 and 0.0193,
      respectively. Samples of "no-mutation detected" were further analyzed by direct
      sequencing for identification of the major haplogroup to which they belong. Along
      with the haplogroup data, we report haplotype data for the 16 Y-STR markers
      included in the AmpFlSTR Yfiler PCR amplification kit (Applied Biosystems). These
      data will be useful in the prediction of haplogroups based on Y-STR haplotypes.

PMID- 20129465
TI  - Optimized manual and automated recovery of amplifiable DNA from tissues preserved
      in buffered formalin and alcohol-based fixative.
AB  - Archival tissue preserved in fixative constitutes an invaluable resource for
      histological examination, molecular diagnostic procedures and for DNA typing
      analysis in forensic investigations. However, available material is often limited
      in size and quantity. Moreover, recovery of DNA is often severely compromised by
      the presence of covalent DNA-protein cross-links generated by formalin, the most
      prevalent fixative. We describe the evaluation of buffer formulations, sample
      lysis regimens and DNA recovery strategies and define optimized manual and
      automated procedures for the extraction of high quality DNA suitable for
      molecular diagnostics and genotyping. Using a 3-step enzymatic digestion protocol
      carried out in the absence of dithiothreitol, we demonstrate that DNA can be
      efficiently released from cells or tissues preserved in buffered formalin or the
      alcohol-based fixative GenoFix. This preparatory procedure can then be integrated
      to traditional phenol/chloroform extraction, a modified manual DNA IQ or
      automated DNA IQ/Te-Shake-based extraction in order to recover DNA for downstream
      applications. Quantitative recovery of high quality DNA was best achieved from
      specimens archived in GenoFix and extracted using magnetic bead capture.

PMID- 20129466
TI  - UV irradiation and autoclave treatment for elimination of contaminating DNA from
      laboratory consumables.
AB  - Laboratories employ various approaches to ensure that their consumables are free
      of DNA contamination. They may purchase pre-treated consumables, perform quality
      control checks prior to casework, and use in-house profile databases for
      contamination detection. It is better to prevent contamination prior to DNA
      typing than identify it after samples are processed. To this end, laboratories
      may UV irradiate or autoclave consumables prior to use but treatment procedures
      are typically based on killing microorganisms and not on the elimination of DNA.
      We report a systematic study of UV and autoclave treatments on the persistence of
      DNA from saliva. This study was undertaken to determine the best decontamination
      strategy for the removal of DNA from laboratory consumables. We have identified
      autoclave and UV irradiation procedures that can eliminate nanogram quantities of
      contaminating DNA contained within cellular material. Autoclaving is more
      effective than UV irradiation because it can eliminate short fragments of
      contaminating DNA more effectively. Lengthy autoclave or UV irradiation
      treatments are required. Depending on bulb power, a UV crosslinker may take a
      minimum of 2h to achieve an effective dose for elimination of nanogram quantities
      of contaminating DNA (>7250mJ/cm(2)). Similarly autoclaving may also take 2h to
      eliminate similar quantities of contaminating DNA. For this study, we used dried
      saliva stains to determine the effective dose. Dried saliva stains were chosen
      because purified DNA as well as fresh saliva are less difficult to eradicate than
      dried stains and also because consumable contamination is more likely to be in
      the form of a collection of dry cells.

PMID- 20129467
TI  - Authentication of forensic DNA samples.
AB  - Over the past twenty years, DNA analysis has revolutionized forensic science, and
      has become a dominant tool in law enforcement. Today, DNA evidence is key to the
      conviction or exoneration of suspects of various types of crime, from theft to
      rape and murder. However, the disturbing possibility that DNA evidence can be
      faked has been overlooked. It turns out that standard molecular biology
      techniques such as PCR, molecular cloning, and recently developed whole genome
      amplification (WGA), enable anyone with basic equipment and know-how to produce
      practically unlimited amounts of in vitro synthesized (artificial) DNA with any
      desired genetic profile. This artificial DNA can then be applied to surfaces of
      objects or incorporated into genuine human tissues and planted in crime scenes.
      Here we show that the current forensic procedure fails to distinguish between
      such samples of blood, saliva, and touched surfaces with artificial DNA, and
      corresponding samples with in vivo generated (natural) DNA. Furthermore,
      genotyping of both artificial and natural samples with Profiler Plus((R)) yielded
      full profiles with no anomalies. In order to effectively deal with this problem,
      we developed an authentication assay, which distinguishes between natural and
      artificial DNA based on methylation analysis of a set of genomic loci: in natural
      DNA, some loci are methylated and others are unmethylated, while in artificial
      DNA all loci are unmethylated. The assay was tested on natural and artificial
      samples of blood, saliva, and touched surfaces, with complete success. Adopting
      an authentication assay for casework samples as part of the forensic procedure is
      necessary for maintaining the high credibility of DNA evidence in the judiciary
      system.

PMID- 20129468
TI  - Characterization of the highly discriminatory loci DYS449, DYS481, DYS518,
      DYS612, DYS626, DYS644 and DYS710.
AB  - During the study of genetic diversity at non-core Y-STRs in South African
      population groups, we identified loci with high discrimination capacity. In this
      study we present a detailed account of the allele diversity, allele sequence
      data, gene diversity, allele frequency spectrum and informativeness for
      assignment in the European English, Asian Indian and Xhosa population groups at
      loci DYS449, DYS481, DYS518, DYS612, DYS626, DYS644 and DYS710. The suitability
      of these loci for forensic, genealogical and evolutionary studies is discussed,
      and nomenclature for loci DYS518, DYS612, DYS626 and DYS644 is suggested.

PMID- 20129469
TI  - Examination of the variability in mixed DNA profile parameters for the
      Identifiler multiplex.
AB  - The interpretation of mixed DNA profiles is often undertaken by determining to
      what extent possible genotype combinations may be eliminated from consideration.
      This requires an understanding of the variability in height or area for the two
      alleles of a heterozygote (heterozygote balance), and in the variability of
      mixture proportion or mixture ratio across loci. We present here empirical data
      to help assess the magnitude of this variability for Identifiler profiles. We
      find that heterozygote balance is affected by peak height as expected and that at
      heights above 267RFU the two peaks of a heterozygote demonstrates a peak height
      ratio between 0.6 and 1.66. For mixtures we introduce a concept, APH, the average
      peak heights of the active alleles. Above an APH of 110RFU mixture proportion
      demonstrated variation no more than 0.2 from the average across loci. Mixture
      ratio variability was affected by both the mixture ratio, M(r) per se and by the
      APH. The function (2APH/(1+M(r))) appears to be a reasonable predictor of the
      variability and approximates the expected peak height of the minor alleles. At
      (2APH/(1+M(r)))> or =300RFU the mixture ratio at a locus is expected to be within
      a factor of 2 of the average across loci.

PMID- 20129470
TI  - Post-coital vaginal sampling with nylon flocked swabs improves DNA typing.
AB  - In the examination of sexual assault cases, DNA typing of vaginal samples mostly
      occurs after differential DNA extraction. Notwithstanding the differential
      extraction method, the DNA profiles from the seminal fraction often show the male
      alleles at low-level in combination with female alleles. This unfavorable ratio
      male to female DNA is due to a limited amount of sperm cells and an overwhelming
      quantity of female cells. In this study, we compared standard cotton and nylon
      flocked swabs for post-coital vaginal sampling. Twelve couples donated 88 vaginal
      swabs - 44 cotton, 44 nylon flocked - which were taken with a time since
      intercourse (TSI) up to 84 h. These vaginal swabs were sorted into categories on
      the basis of the TSI and submitted to (1) microscopic examination for the
      presence of male cells, (2) presumptive tests for the detection of seminal fluid
      and (3) DNA typing. Cellular elution was found to be 6-fold more efficient from
      the nylon flocked swabs. This makes microscopic analysis less time consuming as
      the higher cell yield and better cell morphology simplify detection of male
      cells. Both swab types reveal similar results regarding presumptive tests and
      male DNA typing. Positive presumptive tests (RSID-semen and PSA) were obtained up
      to 60 h TSI and male autosomal profiles up to 72 h TSI. Interestingly, over 50%
      of the samples negative for both presumptive tests resulted in informative male
      STR profiles. After differential extraction, less DNA was left on the nylon
      flocked swabs and more male DNA was isolated. Our results imply that the use of
      nylon flocked swabs for vaginal sampling will improve microscopic analysis and
      DNA typing in the medical forensic investigation of sexual assault cases.

PMID- 20129471
TI  - Forensic analysis of autosomal STR markers using Pyrosequencing.
AB  - Short tandem repeats (STRs) are highly variable, and therefore routinely used in
      forensic investigations for a DNA-based individual identification. The routine
      assay is commonly performed by size separation using capillary electrophoresis,
      but alternative technologies can also be used. In this study, a Pyrosequencing
      assay was developed for analysis of STR markers useful in forensic DNA analysis.
      The assay was evaluated for 10 different STR loci (CSF1PO, TH01, TPOX, D3S1358,
      D5S818, D7S820, D8S1179, D13S317, D16S539 and Penta E) and a total of 114 Swedish
      individuals were genotyped. This genotyping strategy reveal the actual sequence
      and variant alleles were seen at several loci, providing additional information
      compared to fragment size analysis. At the D13S317 locus a T/A SNP located in the
      last repeat unit was observed in 92% of the genotypes. Moreover, an upstream
      flanking SNP at locus D7S820, a SNP within the repeats at D3S1358 and D8S1179 and
      a deletion in the flanking region at locus D5S818 were observed. The
      Pyrosequencing method was first developed for SNP typing and sequencing of
      shorter DNA fragments but the method also provides an alternative method for STR
      analysis of less complex repeats. This assay is suitable for investigation of new
      markers, a rapid compilation of population data and for confirmation of variant
      and new alleles.

PMID- 20129472
TI  - Criterion values for multiplex SNP genotyping by the invader assay.
AB  - We have developed a multiplex, single nucleotide polymorphism (SNP) typing system
      for forensic identification, based on the Invader assay. Using this system,
      fluorescence data for 21 SNP loci were collected and analyzed. We used endpoint
      genotyping, commonly used with the Invader assay, and also developed more
      reliable typing criteria because endpoint typing was occasionally unable to
      clearly identify the genotype of some loci. Analysis of the fluorescence data
      identified criteria that had high reproducibility for each genotype. One such
      criterion is the climbing angle of the curve resulting from two-dimensional plots
      of the two kinds of fluorescence used for the Invader assay. The climbing angle
      was observed at the time during the reaction when either or both of the
      fluorescence intensities increased most significantly. The angles were remarkably
      associated with homozygous genotypes. On the other hand, all heterozygote
      endpoint fluorescence ratios were highly reproducible and had very little
      aberration. These values enabled SNP typing to be more clearly defined compared
      with typing using only the endpoint fluorescence ratio, which is commonly used
      with the Invader assay. The values suggested in this study are easily calculated
      from raw fluorescence data and will be useful for multiplex SNP typing based on
      the Invader assay.

PMID- 20129473
TI  - Generation of DNA profiles from fabrics without DNA extraction.
AB  - DNA profiles can be obtained from fabrics where a person has made direct contact
      with clothing. A standard approach is to cut out a section of the fabric and then
      use a commercially available method to extract and isolate the DNA. Alternative
      methods to isolate DNA include the use of adhesive tape to remove traces of
      cellular material from the fabric prior to extraction. We report on a process to
      obtain full DNA profiles using direct amplification from a range of fabrics. The
      absence of an extraction step both reduces the opportunity for contamination and
      reduces the loss of DNA during the extraction process, increasing the sensitivity
      of the process of generating a DNA profile. The process does not require the use
      of commercially available extraction kits thus reducing the cost of generating a
      DNA profile from trace amounts of starting material. The results are in part
      dependent upon the nature of the fabric used to which the DNA has been
      transferred.

PMID- 20129474
TI  - Genetic variation at 11 autosomal STR loci in the aboriginal people, the Veddahs
      of Sri Lanka.

PMID- 20129475
TI  - Excellence in research: threats from all directions.

PMID- 20129476
TI  - How do we support women and families in breastfeeding?

PMID- 20129477
TI  - The exterminator.

PMID- 20129478
TI  - Are 2 weeks of daily breastfeeding support insufficient to overcome the
      influences of formula?
AB  - OBJECTIVE: To evaluate the effectiveness of proactive telephone breastfeeding
      support in low-income, primiparous, primarily Latina women on 1) duration and
      exclusivity of breastfeeding, 2) satisfaction with feeding, 3) rationale for
      discontinuing breastfeeding and 4) health care utilization. METHODS: Randomized
      controlled trial comparing usual care to 2 weeks of daily telephone calls by
      nurses by using culturally informed scripted protocols; and qualitative study of
      focused interviews on a sample of women in the intervention group (n = 40).
      RESULTS: Breastfeeding duration and exclusivity rates, feeding method
      satisfaction, and reasons for stopping breastfeeding did not differ significantly
      between intervention (n = 161) and control (n = 180) groups, with 74% of both
      breastfeeding at 1 month and 28% and 37%, respectively, at 6 months. Insufficient
      milk supply was the main reason for stopping in both groups. Intervention infants
      were less likely to have a sick visit by 1 month (25%) than controls (35%, P =
      .05). Qualitative interviews revealed that the intervention was informative and
      helpful, with breastfeeding reported as healthier but harder; formula was a good
      alternative. Intervention mothers reporting < or =2 supplemental formula feedings
      on day 4 were more likely than mothers reporting > or =3 supplemental feedings to
      breastfeed at 1 month (odds ratio 7.7; 95% confidence interval 2.4-24.3).
      CONCLUSIONS: Two weeks of daily telephone support did not increase breastfeeding
      duration but was associated with a decrease in sick visits in the first month.
      Early supplementation and the perception of formula as a good alternative to
      dealing with the breastfeeding difficulties appeared to be factors in failure of
      the intervention.

PMID- 20129479
TI  - Factors associated with detection and receipt of treatment for youth with
      depression and anxiety disorders.
AB  - OBJECTIVE: Anxiety and depression are common among youth and are associated with
      significant morbidity. Few youth with depression are diagnosed and receive
      treatment for these disorders. The purpose of this study was to examine the rate
      of recognition and management among an insured population and the factors
      associated with evidence of detection among youth. METHODS: Structured mental
      health interviews assessing depression and anxiety diagnoses were completed with
      a random sample of 581 youth (age range 11-17 years) from an integrated health
      care system. Administrative data on medical and pharmacy services were used to
      examine any evidence of detection by the medical system in the prior 12 months.
      RESULTS: Fifty-one youth met criteria for an anxiety or depressive disorder.
      Twenty-two percent of these youth with an anxiety or depressive disorder as
      defined in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      had evidence of detection or treatment. Factors associated with detection and
      treatment included having diagnosis of a depressive disorder (with or without an
      anxiety disorder), more depressive symptoms, greater functional impairment, a
      higher number of primary care visits in the prior year, and higher parent
      reported externalizing symptoms. On multivariate analysis, having more depressive
      symptoms and a higher number of primary care visits were significant predictors
      of detection and receipt of treatment. CONCLUSIONS: The rate of detection and
      treatment of anxiety and depressive disorders is very low in this age group and
      suggests a need for increased focus on detection, particularly in light of recent
      evidence suggesting decreases in diagnosis and treatment among youth following
      the black box warning regarding antidepressant medications.

PMID- 20129480
TI  - Socioeconomic risk factors for mental health problems in 4-5-year-old children:
      Australian population study.
AB  - OBJECTIVE: To describe the extent to which parent- and teacher-reported child
      mental health problems vary by different indicators of socioeconomic status.
      METHODS: Participants were 4-5-year-old children in the Longitudinal Study of
      Australian Children (LSAC). Parents (N = 4968) and teacher (N = 3245) completed
      the 3-4-year-old version of Strengths and Difficulties Questionnaire (SDQ).
      Parents also reported the socioeconomic indicators of income, education,
      employment, and family composition (1- vs 2-parent families). Logistic regression
      models were used to predict SDQ total difficulties and each of the 4 SDQ
      subscales problems, as reported by parents and by teacher, and considered all
      putative socioeconomic status (SES) predictor variables simultaneously. RESULTS:
      The proportions of children scoring in the abnormal range varied according to SES
      indicator and mental health subscale. All of the SES indicators independently
      predicted parent-reported child mental health problems, although odds ratios were
      generally small to moderate (1.2 to 2.4), and not all reached statistical
      significance. Low income and parent education showed larger associations than
      sole parenthood or unemployment. The pattern for teachers was similar, though
      less consistent. Behavioral problems showed stronger associations with social
      disadvantage than emotional problems. CONCLUSIONS: Research examining pathways to
      young children's mental health should include diverse measures of SES,
      particularly of family income and education. The fact that mental health problems
      were most strongly associated with parent education and income should be of
      interest to policy makers because education and income reflect investments in the
      lives of our participants' parents during their own childhood and adolescence.

PMID- 20129481
TI  - Impact of managed care on publicly insured children with special health care
      needs.
AB  - OBJECTIVE: The aim of this review was to evaluate the impact of managed care on
      publicly insured children with special health care needs (CSHCN). METHODS: We
      conducted a review of the extant literature. Using a formal computerized search,
      with search terms reflecting 7 specific outcome categories, we summarized study
      findings and study quality. RESULTS: We identified 13 peer-reviewed articles that
      evaluated the impact of Medicaid and State Children's Health Insurance program
      (SCHIP) Managed Care (MSMC) on health services delivery to populations of CSHCN,
      with all studies observational in design. Considered in total, the available
      scientific evidence is varied. Findings concerning care access demonstrate a
      positive effect of MSMC; findings concerning care utilization were mixed. Little
      information was identified concerning health care quality, satisfaction, costs,
      or health status, whereas no study yielded evidence on family impact. CONCLUSION:
      The available studies suggest that the evaluated record of MSMC for CSHCN has
      been mixed, with considerable heterogeneity in the definition of CSHCN, program
      design, and measured outcomes. These findings suggest caution should be exercised
      in implementing MSMC for CSHCN and that greater emphasis on health outcomes and
      cost evaluations is warranted.

PMID- 20129482
TI  - Comparing medical homes for children with ADHD and asthma.
AB  - OBJECTIVE: The aims of our study were, among children with attention
      deficit/hyperactivity disorder (ADHD) compared with children with asthma: 1) to
      assess characteristics associated with parent report of having a medical home for
      children with either of these 2 conditions; 2) to determine whether, controlling
      for these characteristics, the likelihood of having a medical home differs
      between children with ADHD and asthma; and 3) to identify the specific components
      of a medical home that are lacking for children with these 2 conditions. METHODS:
      Cross-sectional analysis of the National Survey of Children with Special Health
      Care Needs, 2005-2006 (NS-CSHCN) was used. The outcome variable was parent report
      of their child's practice having specific attributes of the medical home. We used
      multivariate logistic regression to test whether the likelihood of having a
      medical home and its components differed for children with ADHD in comparison to
      children with asthma. RESULTS: The NS-CSHCN interviewed parents of 11 674
      children with ADHD and 13 517 children with asthma aged between 4 to 17 years.
      Significantly fewer children with ADHD compared with children with asthma have a
      medical home (OR [odds ratio] 0.68; P < .001). Specifically, parents reported
      differences in receiving family-centered (OR 0.79; P < .001) and coordinated care
      (OR 0.59; P < .001). CONCLUSION: Parents of children with ADHD report worse
      performance across key dimensions of primary care compared with parents of
      children with asthma. For primary care to be optimally effective in addressing
      the needs of children with ADHD, efforts to significantly strengthen these key
      dimensions are needed.

PMID- 20129483
TI  - Practice characteristics that influence nonurgent pediatric emergency department
      utilization.
AB  - OBJECTIVE: The goal of this study was to determine what characteristics of a
      primary care pediatric practice are associated with nonurgent use of the
      pediatric emergency department (PED). METHODS: Primary care practice
      characteristics were prospectively collected from 33 practices. Nonurgent and
      urgent visits to the PED for patients from these practices were analyzed
      retrospectively. A discriminant analysis classification model was used to
      identify practice characteristics that were associated with nonurgent versus
      urgent utilization of the PED. RESULTS: Patients in the network of 33 practices
      accounted for 31 076 visits to the PED during the 12-month study period, 47% of
      which were classified as nonurgent. Based on the discriminant analysis
      classification model, discriminant patterns that predict the frequency of
      nonurgent utilization included the percentage of patients with Medicaid, total
      available sick slots to see patients per physician, closer distance to the PED,
      whether or not the nurse triage line notified all on-call physicians of
      disposition to the PED, whether it is practice policy to accept all walk-in sick
      visits, and ability of practice to have same-day turnaround of laboratory tests.
      CONCLUSIONS: Nonurgent utilization of the PED by patients in a specific primary
      care practice can be predicted based on discriminant practice characteristics,
      several of which may be modifiable. Use of these predictive rules can be used to
      optimize pediatric services and policy to help mitigate the high volume of PED
      nonurgent visitation. Focused interventions on practice characteristics of
      significance may help reduce PED overcrowding and improve continuity of care.

PMID- 20129484
TI  - Transplantation in Parkinson's disease: will mesenchymal stem cells help to
      reenter the clinical arena?

PMID- 20129485
TI  - The role of prostacyclin in lung cancer.
AB  - Prostanoids are bioactive lipids that interact with 7-membrane-spanning G-protein
      coupled receptors on target cells to impart their biologic effects. They include
      prostaglandins, prostacyclin, and thromboxane. Prostanoids are widely
      distributed; mediate several diverse biologic effects like platelet aggregation
      and smooth-muscle contraction; and are known to be involved in allergies,
      acquired immunity, and cancer metastasis. Prostanoids have also been associated
      with breast and endometrial cancer promotion, and with the inhibition of
      melanoma. The role of prostanoids in the development of lung disease has been
      poorly understood. In particular, prostacyclin possesses significant anti
      inflammatory and antimetastatic properties and is the main product of
      cyclooxygenase-2 activity in the lung. In fact, the balance of the various
      members of the prostanoids family, specifically the prostaglandins PGE(2) and
      prostacyclin (PGI(2)), seems to play an increasingly important role in the
      development of lung cancer. Gaining a better understanding of prostanoids and
      their associated pathways is critical to the future development of molecular
      based and pharmaceutical treatments of lung disease.

PMID- 20129486
TI  - Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem
      cell transplantation in Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease for which
      stem cell research has created hope in the last few years. Seven PD patients aged
      22 to 62 years with a mean duration of disease 14.7+/-7.56 years were enrolled to
      participate in the prospective, uncontrolled, pilot study of single-dose,
      unilateral transplantation of autologous bone-marrow-derived mesenchymal stem
      cells (BM-MSCs). The BM-MSCs were transplanted into the sublateral ventricular
      zone by stereotaxic surgery. Patients were followed up for a period that ranged
      from 10 to 36 months. The mean baseline "off" score was 65+/-22.06, and the mean
      baseline "on" score was 50.6+/-15.85. Three of 7 patients have shown a steady
      improvement in their "off"/"on" Unified Parkinson's Disease Rating Scale (UPDRS).
      The mean "off" score at their last follow-up was 43.3 with an improvement of
      22.9% from the baseline. The mean "on" score at their last follow-up was 31.7,
      with an improvement of 38%. Hoehn and Yahr (H&Y) and Schwab and England (S&E)
      scores showed similar improvements from 2.7 and 2.5 in H&Y and 14% improvement in
      S&E scores, respectively. A subjective improvement was found in symptoms like
      facial expression, gait, and freezing episodes; 2 patients have significantly
      reduced the dosages of PD medicine. These results indicate that our protocol
      seems to be safe, and no serious adverse events occurred after stem-cell
      transplantation in PD patients. The number of patients recruited and the
      uncontrolled nature of the trial did not permit demonstration of effectiveness of
      the treatment involved. However, the results encourage future trials with more
      patients to demonstrate efficacy.

PMID- 20129487
TI  - Sex difference in cardiometabolic risk profile and adiponectin expression in
      subjects with visceral fat obesity.
AB  - This study investigates the sex difference of cardiometabolic risk profiles in
      subjects with visceral fat obesity (VFO) but normal waist circumference (WC).
      VFO, which is defined as visceral adipose tissue (VAT) area more than 100 cm(2)
      by computed tomography (CT), and cardiometabolic risk profiles were assessed in
      437 subjects with normal WC (197 female subjects and 240 male subjects). The
      expression of adiponectin and its receptor in abdominal adipose tissue was
      measured in a subgroup of the subjects. Compared with the male subjects, female
      subjects had a larger abdominal subcutaneous adipose tissue (SAT) area (158+/-56
      vs 116+/-38 cm(2), P<0.01), smaller VAT area (67+/-44 vs 78+/-33 cm(2); P<0.01),
      and lower prevalence of VFO (12.2 vs 24.2%, P<0.001). This finding was
      accompanied by upregulated expressions of adiponectin and its receptor in
      abdominal adipose tissue in female subjects. Without VFO, the risk profiles were
      not significantly different between male subjects and female subjects. Although
      risk factors were increased and intensified in both sexes in the presence of VFO,
      female subjects with VFO were associated with greater cardiometabolic risks than
      male subjects. A regression analysis indicates the ratio of VAT/SAT for female
      subjects, whereas VAT and age for male subjects were independently associated
      with clustering of multiple cardiometabolic risk factors. In conclusion, in
      subjects with normal WC, the prevalence of VFO is lower and the expression of
      adiponectin and its receptor is higher in female subjects compared with male
      subjects. Although VFO was associated with increased risk in both sexes, the risk
      profile in female subjects with VFO was more pronounced.

PMID- 20129488
TI  - Early physiologic responses to hemorrhagic hypotension.
AB  - The identification of early indicators of hemorrhagic hypotension (HH) severity
      may support early therapeutic approaches and bring insights into possible
      mechanistic implications. However, few systematic investigations of physiologic
      variables during early stages of hemorrhage are available. We hypothesized that,
      in certain subjects, early physiologic responses to blood loss are associated
      with the ability to survive hemorrhage levels that are lethal to subjects that do
      not present the same responses. Therefore, we examine the relevance of specific
      systemic changes during and after the bleeding phase of HH. Stepwise hemorrhage,
      representing prehospital situations, was performed in 44 rats, and measurements
      were made after each step. Heart and respiratory rates, arterial and venous blood
      pressures, gases, acid-base status, glucose, lactate, electrolytes, hemoglobin,
      O(2) saturation, tidal volume, and minute volume were measured before, during,
      and after bleeding 40% of the total blood volume. Fifty percent of rats survived
      100 min (survivors, S) or longer; others were considered nonsurvivors (NS). Our
      findings were as follows: (1) S and NS subjected to a similar hemorrhage
      challenge showed significantly different responses during nonlethal levels of
      bleeding; (2) survivors showed higher blood pressure and ventilation than NS; (3)
      although pH was lower in NS at later stages, changes in bicarbonate and base
      excess occurred already during the hemorrhage phase and were higher in NS; and
      (4) plasma K(+) levels and glucose extraction were higher in NS. We conclude that
      cardiorespiratory and metabolic responses, essential for the survival at HH, can
      differentiate between S and NS even before a lethal bleeding was reached.

PMID- 20129489
TI  - Development of an improved assay system for activated platelet counts and
      evaluation by aspirin monitoring.
AB  - Platelets represent a linkage among inflammation, thrombosis, and atherogenesis,
      and enhanced platelet activation is regarded as a risk for thrombotic disorders.
      The level of P-selectin expressed (CD62P) on the platelet surface is a useful
      marker of activated platelets (aPLT). Although CD62P has been measured briefly by
      flow cytometry using an anti-CD62P antibody, the assay remains imprecise and we
      tried to establish stable conditions for its measurement. The levels of aPLT are
      increased significantly by many factors, such as meals, sampling and keeping
      conditions, centrifugation, and the timing of fixation. For optimal results,
      sampling should be performed quickly in a K(2)-ethylenediaminetetraacetic acid
      (EDTA) containing a sample tube, and whole blood should be fixed with 666 mmol/L
      formaldehyde plus 167 mmol/L glyoxal for 5 min. After washing with phosphate
      buffered saline (PBS), the fixed platelets were reacted with anti-CD62P antibody
      for 20 min and measured by flow-cytometric detection for aPLT. The coefficient of
      variation of our aPLT assay was 10.4%. We also examined basic experiments to test
      the clinical application of our aPLT assay by monitoring aspirin therapy. The
      levels of aPLT after the administration of aspirin for 3 days were significantly
      lower than those in the group that did not receive aspirin. These results suggest
      that the aPLT assay is an effective analytical procedure for measuring platelet
      reactivity.

PMID- 20129490
TI  - Arsenic trioxide-mediated antiplatelet activity: pivotal role of the
      phospholipase C gamma 2-protein kinase C-p38 MAPK cascade.
AB  - Arsenic trioxide produces high rates of complete clinical remission in patients
      with relapsed/refractory acute promyelocytic leukemia. Platelet activation is
      relevant in a variety of acute thrombotic events and coronary heart diseases. Few
      studies have examined the effects of arsenic trioxide on platelets, and the
      mechanisms underlying the signaling pathways remain obscure. The aim of this
      study was to examine systematically the detailed mechanisms of arsenic trioxide
      in preventing platelet activation. Arsenic trioxide (5 micromol/L) exhibited more
      potent activity at inhibiting collagen (1 microg/mL)-induced platelet aggregation
      than other agonists. Arsenic trioxide (15 and 25 micromol/L) inhibited collagen
      induced platelet activation accompanied by [Ca(+2)]i mobilization, thromboxane
      A(2) (TxA(2)) formation, phospholipase C (PLC)gamma 2 phosphorylation, and
      protein kinase C (PKC) activation. Arsenic trioxide (15 and 25 micromol/L) did
      not significantly affect cyclic nucleotide-induced vasodilator-stimulated
      phosphoprotein phosphorylation. Moreover, arsenic trioxide markedly inhibited p38
      mitogen-activated protein kinase (MAPK) but not JNK1/2 or ERK2 phosphorylation in
      washed platelets. Arsenic trioxide also markedly reduced hydroxyl radical (OH(.))
      formation in the erythrocyte sedimentation rate (ESR) study. The most important
      findings of this study suggest that the inhibitory effect of arsenic trioxide
      possibly involves inhibition of the PLC gamma 2-PKC-p38 MAPK cascade, thereby
      leading to inhibition of [Ca(+2)]i or free radical formation, and finally the
      inhibition of platelet aggregation.

PMID- 20129491
TI  - Traumatic brain injury: therapeutic challenges and new directions.

PMID- 20129492
TI  - Cell death mechanisms and modulation in traumatic brain injury.
AB  - Cell death after traumatic brain injury (TBI) is a major cause of neurological
      deficits and mortality. Understanding the mechanisms of delayed post-traumatic
      cell loss may lead to new therapies that improve outcome. Although TBI induces
      changes in multiple cell types, mechanisms of neuronal cell death have been the
      predominant focus. Recent work has emphasized the diversity of neuronal death
      phenotypes, which have generally been defined by either morphological or
      molecular changes. This diversity has led to confusing and at times contradictory
      nomenclature. Here we review the historical basis of proposed definitions of
      neuronal cell death, with the goal of clarifying critical research questions and
      implications for therapy in TBI. We believe that both morphological and molecular
      features must be used to clarify post-traumatic cell death and related
      therapeutic targets. Further, we underscore that the most effective
      neuroprotective strategies will need to target multiple pathways to reflect the
      regional and temporal changes underlying diverse neuronal cell death phenotypes.

PMID- 20129493
TI  - Mitochondrial damage: a target for new therapeutic horizons.
AB  - Traumatic brain injury (TBI) represents a leading cause of death and morbidity,
      as well as a considerable social and economical burden in western countries, and
      has thus emerged as a formidable therapeutic challenge. Yet despite tremendous
      efforts enlightening the mechanisms of neuronal death, hopes for the "magic
      bullet" have been repeatedly deceived, and TBI management has remained focused on
      the control of increased intracranial pressure. Indeed, impairment of cerebral
      metabolism is traditionally attributed to impaired oxygen delivery mediated by
      reduced cerebral perfusion in the swollen cerebral parenchyma. Although
      intuitively appealing, this hypothesis is not entirely supported by physiological
      facts and does not take into consideration mitochondrial dysfunction that has
      been repeatedly reported in both human and animal TBI. Although the nature and
      origin of the events leading to mitochondrial damage may be different, most share
      a permeabilization of mitochondrial membrane, which therefore may represent a
      logical target for new therapeutic strategies. Therefore, the proteins mediating
      these events may represent promising targets for new TBI therapies. Furthermore,
      mimicking anti-apoptotic proteins, such as Bcl-2 or XIAP, or inhibiting
      mitochondrial pro-apoptotic proteins, such as Smac/DIABLO, Omi/HTRA2, and ARTS
      (septin 4 isoform 2) may represent useful novel therapeutic strategies. This
      review focuses on mechanisms of the mitochondrial membrane permeabilization and
      its consequences and discusses the current and possible future therapeutic
      implications of this key event of neuronal death.

PMID- 20129494
TI  - Involvement of pro- and anti-inflammatory cytokines and chemokines in the
      pathophysiology of traumatic brain injury.
AB  - Despite dramatic improvements in the management of traumatic brain injury (TBI),
      to date there is no effective treatment available to patients, and morbidity and
      mortality remain high. The damage to the brain occurs in two phases, the initial
      primary phase being the injury itself, which is irreversible and amenable only to
      preventive measures to minimize the extent of damage, followed by an ongoing
      secondary phase, which begins at the time of injury and continues in the ensuing
      days to weeks. This delayed phase leads to a variety of physiological, cellular,
      and molecular responses aimed at restoring the homeostasis of the damaged tissue,
      which, if not controlled, will lead to secondary insults. The development of
      secondary brain injury represents a window of opportunity in which pharmaceutical
      compounds with neuroprotective properties could be administered. To establish
      effective treatments for TBI victims, it is imperative that the complex molecular
      cascades contributing to secondary injury be fully elucidated. One pathway known
      to be activated in response to TBI is cellular and humoral inflammation.
      Neuroinflammation within the injured brain has long been considered to intensify
      the damage sustained following TBI. However, the accumulated findings from years
      of clinical and experimental research support the notion that the action of
      inflammation may differ in the acute and delayed phase after TBI, and that
      maintaining limited inflammation is essential for repair. This review addresses
      the role of several cytokines and chemokines following focal and diffuse TBI, as
      well as the controversies around the use of therapeutic anti-inflammatory
      treatments versus genetic deletion of cytokine expression.

PMID- 20129495
TI  - Calpain as a therapeutic target in traumatic brain injury.
AB  - The family of calcium-activated neutral proteases, calpains, appears to play a
      key role in neuropathologic events following traumatic brain injury (TBI).
      Neuronal calpain activation has been observed within minutes to hours after
      either contusive or diffuse brain trauma in animals, suggesting that calpains are
      an early mediator of neuronal damage. Whereas transient calpain activation
      triggers numerous cell signaling and remodeling events involved in normal
      physiological processes, the sustained calpain activation produced by trauma is
      associated with neuron death and axonal degeneration in multiple models of TBI.
      Nonetheless, the causal relationship between calpain activation and neuronal
      death is not fully understood. Much remains to be learned regarding the
      endogenous regulatory mechanisms for controlling calpain activity, the roles of
      different calpain isoforms, and the in vivo substrates affected by calpain.
      Detection of stable proteolytic fragments of the submembrane cytoskeletal protein
      alphaII-spectrin specific for cleavage by calpains has been the most widely used
      marker of calpain activation in models of TBI. More recently, these protein
      fragments have been detected in the cerebrospinal fluid after TBI, driving
      interest in their potential utility as TBI-associated biomarkers. Post-traumatic
      inhibition of calpains, either direct or indirect through targets related to
      intracellular calcium regulation, is associated with attenuation of functional
      and behavioral deficits, axonal pathology, and cell death in animal models of
      TBI. This review focuses on the current state of knowledge of the role of
      calpains in TBI-induced neuropathology and effectiveness of calpain as a
      therapeutic target in the acute post-traumatic period.

PMID- 20129496
TI  - The evidence for hypothermia as a neuroprotectant in traumatic brain injury.
AB  - This article reviews published experimental and clinical evidence for the
      benefits of modest hypothermia in the treatment of traumatic brain injury (TBI).
      Therapeutic hypothermia has been reported to improve outcome in several animal
      models of CNS injury and has been successfully translated to specific patient
      populations. A PubMed search for hypothermia and TBI was conducted, and important
      papers were selected for review. The research summarized was conducted at major
      academic institutions throughout the world. Experimental studies have emphasized
      that hypothermia can affect multiple pathophysiological mechanisms thought to
      participate in the detrimental consequences of TBI. Published data from several
      relevant clinical trials on the use of hypothermia in severely injured TBI
      patients are also reviewed. The consequences of mild to moderate levels of
      hypothermia introduced by different strategies to the head-injured patient for
      variable periods of time are discussed. Both experimental and clinical data
      support the beneficial effects of modest hypothermia following TBI in specific
      patient populations. Following on such single-institution studies, positive
      findings from multicenter TBI trials will be required before this experimental
      treatment can be considered standard of care.

PMID- 20129497
TI  - Antioxidant therapies for traumatic brain injury.
AB  - Free radical-induced oxidative damage reactions, and membrane lipid peroxidation
      (LP), in particular, are among the best validated secondary injury mechanisms in
      preclinical traumatic brain injury (TBI) models. In addition to the disruption of
      the membrane phospholipid architecture, LP results in the formation of cytotoxic
      aldehyde-containing products that bind to cellular proteins and impair their
      normal functions. This article reviews the progress of the past three decades in
      regard to the preclinical discovery and attempted clinical development of
      antioxidant drugs designed to inhibit free radical-induced LP and its neurotoxic
      consequences via different mechanisms including the O(2)(*-) scavenger superoxide
      dismutase and the lipid peroxidation inhibitor tirilazad. In addition, various
      other antioxidant agents that have been shown to have efficacy in preclinical TBI
      models are briefly presented, such as the LP inhibitors U83836E, resveratrol,
      curcumin, OPC-14177, and lipoic acid; the iron chelator deferoxamine and the
      nitroxide-containing antioxidants, such as alpha-phenyl-tert-butyl nitrone and
      tempol. A relatively new antioxidant mechanistic strategy for acute TBI is aimed
      at the scavenging of aldehydic LP byproducts that are highly neurotoxic with
      "carbonyl scavenging" compounds. Finally, it is proposed that the most effective
      approach to interrupt posttraumatic oxidative brain damage after TBI might
      involve the combined treatment with mechanistically complementary antioxidants
      that simultaneously scavenge LP-initiating free radicals, inhibit LP propagation,
      and lastly remove neurotoxic LP byproducts.

PMID- 20129498
TI  - Statins in traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a common cause of long-term neurological
      morbidity, with devastating personal and societal consequences. At present, no
      pharmacological intervention clearly improves outcomes, and therefore a
      compelling unmet clinical need remains. 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors, or "statins," offer a potential novel therapeutic strategy
      for TBI. Statins are well tolerated, easy to administer, and have a long clinical
      track record in critically ill patients. Their side effects are well defined and
      easily monitored. Preclinical studies have shown significant benefit of statins
      in models of TBI and related disease processes, including cerebral ischemia,
      intracerebral hemorrhage, and subarachnoid hemorrhage. In fact, multiple
      mechanisms have been defined by which statins may exert benefit after acute brain
      injury. Statins are currently positioned to be translated into clinical trials in
      acute brain injury and have the potential to improve outcomes after TBI.

PMID- 20129499
TI  - Substance P antagonists as a therapeutic approach to improving outcome following
      traumatic brain injury.
AB  - Although a number of secondary injury factors are known to contribute to the
      development of morphological injury and functional deficits following traumatic
      brain injury, accumulating evidence has suggested that neuropeptides, and in
      particular substance P, may play a critical role. Substance P is released early
      following acute injury to the CNS as part of a neurogenic inflammatory response.
      In so doing, it facilitates an increase in the permeability of the blood-brain
      barrier and the development of vasogenic edema. At the cellular level, substance
      P has been shown to directly result in neuronal cell death; functionally,
      substance P has been implicated in learning and memory, mood and anxiety, stress
      mechanisms, emotion-processing, migraine, emesis, pain, and seizures, all of
      which may be adversely affected after brain injury. Inhibition of post-traumatic
      substance P activity, either by preventing release or by antagonism of the
      neurokinin-1 receptor, has consistently resulted in a profound decrease in
      development of edema and marked improvements in functional outcome. This review
      summarizes the current evidence supporting a role for substance P in acute brain
      injury.

PMID- 20129500
TI  - Traumatic brain injury and aging: is a combination of progesterone and vitamin D
      hormone a simple solution to a complex problem?
AB  - Although progress is being made in the development of new clinical treatments for
      traumatic brain injury (TBI), little is known about whether such treatments are
      effective in older patients, in whom frailty, prior medical conditions, altered
      metabolism, and changing sensitivity to medications all can affect outcomes
      following a brain injury. In this review we consider TBI to be a complex, highly
      variable, and systemic disorder that may require a new pharmacotherapeutic
      approach, one using combinations or cocktails of drugs to treat the many
      components of the injury cascade. We review some recent research on the role of
      vitamin D hormone and vitamin D deficiency in older subjects, and on the
      interactions of these factors with progesterone, the only treatment for TBI that
      has shown clinical effectiveness. Progesterone is now in phase III multicenter
      trial testing in the United States. We also discuss some of the potential
      mechanisms and pathways through which the combination of hormones may work,
      singly and in synergy, to enhance survival and recovery after TBI.

PMID- 20129501
TI  - Use of magnesium in traumatic brain injury.
AB  - Depletion of magnesium is observed in animal brain and in human blood after brain
      injury. Treatment with magnesium attenuates the pathological and behavioral
      changes in rats with brain injury; however, the therapeutic effect of magnesium
      has not been consistently observed in humans with traumatic brain injury (TBI).
      Secondary brain insults are observed in patients with brain injury, which
      adversely affect clinical outcome. Systemic administration studies in rats have
      shown that magnesium enters the brain; however, inducing hypermagnesemia in
      humans did not concomitantly increase magnesium levels in the CSF. We hypothesize
      that the neuroprotective effects of magnesium in TBI patients could be observed
      by increasing its brain bioavailability with mannitol. Here, we review the role
      of magnesium in brain injury, preclinical studies in brain injury, clinical
      safety and efficacy studies in TBI patients, brain bioavailability studies in
      rat, and pharmacokinetic studies in humans with brain injury. Neurodegeneration
      after brain injury involves multiple biochemical pathways. Treatment with a
      single agent has often resulted in poor efficacy at a safe dose or toxicity at a
      therapeutic dose. A successful neuroprotective therapy needs to be aimed at
      homeostatic control of these pathways with multiple agents. Other pharmacological
      agents, such as dexanabinol and progesterone, and physiological interventions,
      with hypothermia and hyperoxia, have been studied for the treatment of brain
      injury. Treatment with magnesium and hypothermia has shown favorable outcome in
      rats with cerebral ischemia. We conclude that coadministration of magnesium and
      mannitol with pharmacological and physiological agents could be an effective
      neuroprotective regimen for the treatment of TBI.

PMID- 20129503
TI  - Clinical trials in traumatic brain injury: past experience and current
      developments.
AB  - In this article, we review past and current experience in clinical trials of
      traumatic brain injuries (TBIs), we discuss limitations and challenges, and we
      summarize current directions. The focus is on severe and moderate TBIs. A
      systematic literature search of the years from 1980 to 2009 revealed 27 large
      phase III trials in TBI; we were aware of a further 6 unpublished trials.
      Analysis of these 33 trials yielded interesting observations: There was a peak
      incidence of trial initiations that occurred in the mid-1990s with a sharp
      decline during the period from 2000 to 2004. Most trials that reported a
      significant treatment effect were studies on a therapeutic strategy (e.g.,
      decompressive craniectomy, hypothermia), and these were single-center studies.
      Increasingly, studies have been shifting toward the Far East. The currently
      existing trial registries permit insight into ongoing or recently conducted
      trials. Compared with the past decade, the number of studies on neuroprotective
      agents taken forward into efficacy-oriented studies is low. In contrast, the
      number of studies on therapeutic strategies appears to be increasing again. The
      disappointing results in trials on neuroprotective agents in TBI have led to a
      critical reappraisal of clinical trial methodology. This has resulted in
      recommendations for preclinical workup and has triggered extensive analysis on
      approaches to improve the design and analysis of clinical trials in TBI. An
      interagency initiative toward standardization on selection and coding of data
      elements across the broad spectrum of TBI is ongoing, and will facilitate
      comparison of research findings across studies and encourage high-quality meta
      analysis of individual patient data in the future.

PMID- 20129504
TI  - IMPACT recommendations for improving the design and analysis of clinical trials
      in moderate to severe traumatic brain injury.
AB  - Clinical trials in traumatic brain injury (TBI) pose complex methodological
      challenges, largely related to the heterogeneity of the population. The
      International Mission on Prognosis and Clinical Trial Design in TBI study group
      has explored approaches for dealing with this heterogeneity with the aim to
      optimize clinical trials in TBI. Extensive prognostic analyses and simulation
      studies were conducted on individual patient data from eight trials and three
      observational studies. Here, we integrate the results of these studies into the
      International Mission on Prognosis and Clinical Trial Design in TBI
      recommendations for design and analysis of trials in TBI: Details of the major
      baseline prognostic characteristics should be provided in every report on a TBI
      study; in trials they should be differentiated per treatment group. We also
      advocate the reporting of the baseline prognostic risk as determined by validated
      prognostic models. Inclusion criteria should be as broad as is compatible with
      the current understanding of the mechanisms of action of the intervention being
      evaluated. This will maximize recruitment rates and enhance the generalizability
      of the results. The statistical analysis should incorporate prespecified
      covariate adjustment to mitigate the effects of the heterogeneity. The
      statistical analysis should use an ordinal approach, based on either sliding
      dichotomy or proportional odds methodology. Broad inclusion criteria,
      prespecified covariate adjustment, and an ordinal analysis will promote an
      efficient trial, yielding gains in statistical efficiency of more than 40%. This
      corresponds to being able to detect a 7% treatment effect with the same number of
      patients needed to demonstrate a 10% difference with an unadjusted analysis based
      on the dichotomized Glasgow outcome scale.

PMID- 20129502
TI  - Biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy for
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) remains a serious health concern, and TBI is one of
      the leading causes of death and disability, especially among young adults.
      Although preventive education, increased usage of safety devices, and TBI
      management have dramatically increased the potential for surviving a brain
      injury, there is still a need to develop reliable methods to diagnose TBI, the
      secondary pathologies associated with TBI, and predicting the outcomes of TBI.
      Biomarkers (changes of amount or activity in a biomolecule that reflect injury or
      disease) have shown promise in the diagnosis of several conditions, including
      cancer, heart failure, infection, and genetic disorders. A variety of proteins,
      small molecules, and lipid products have been proposed as potential biomarkers of
      brain damage from TBI. Although some of these changes have been reported to
      correlate with mortality and outcome, further research is required to identify
      prognostic biomarkers. This need is punctuated in mild injuries that cannot be
      readily detected using current techniques, as well as in defining patient risk
      for developing TBI-associated secondary injuries.

PMID- 20129506
TI  - Physiatry: What's the end game?

PMID- 20129507
TI  - PASSOR Legacy Award Lecture 2009: The past, present, and future of
      musculoskeletal ultrasound in physiatry.

PMID- 20129508
TI  - Upper limb nerve entrapment syndromes in veterans with lower limb amputations.
AB  - OBJECTIVE: To examine the prevalence and severity of upper limb entrapment
      syndromes in a sample of veterans with lower limb amputations. DESIGN: A
      descriptive survey, pilot study. SETTING: 2008 National Disabled Veterans Winter
      Sports Clinic. PARTICIPANTS: Twenty participants with various lower limb
      amputations. METHODS: All study participants completed a questionnaire that
      included symptoms of both upper limbs, medical history, time since amputation,
      medication history, use of assistive technology, and wheelchair characteristics.
      A physical examination and electrodiagnostic testing were then performed on each
      participant. The physical examination included an assessment of bilateral upper
      limb weakness or sensory abnormalities, thenar/hypothenar atrophy, deep tendon
      reflexes, Tinel test of the wrist and elbow, and the Phalen maneuver. All nerve
      conduction studies were performed by an American Board of Electrodiagnostic
      Medicine-certified physiatrist. OUTCOME MEASURES: Correlation between symptoms,
      examination findings, and electrodiagnostic findings with the participant's
      demographic data in the questionnaire. RESULTS: Twenty participants (19 men and 1
      woman) were enrolled in the study, with a total of 38 upper limbs evaluated. The
      mean age of the study population was 59 +/- 13 years, with an average of 23 years
      since the amputation. Sixteen (80%) of 20 participants had electrodiagnostic
      findings consistent with median neuropathy across the wrist (26/38 affected
      limbs, 6 participants with unilateral and 10 with bilateral findings), and 14
      (70%) of 20 participants had ulnar entrapment neuropathy across the elbow (22/38
      affected limbs, 6 participants with unilateral and 8 with bilateral findings).
      Several participants (6 of 20, 30%) were found to have electrodiagnostic evidence
      of ulnar entrapment neuropathy across the wrist (10 of 38 affected limbs, 2
      participants unilateral and 4 bilateral findings). CONCLUSION: A high number of
      veterans with lower limb amputations presented with upper limb nerve entrapment
      syndromes. Careful attention to these nerve entrapment syndromes in lower limb
      amputees is necessary because the symptoms may be confounded by other chronic
      pain-related disorders.

PMID- 20129509
TI  - A pilot study of vitamin D and balance characteristics in middle-aged, healthy
      individuals.
AB  - OBJECTIVE: To examine what relationship exists between 25-hydroxyvitamin D (25
      OHD) levels and postural competency in the middle-aged, healthy individual.
      DESIGN: A community convenience sample. SETTING: Major medical center employees.
      SUBJECTS: Thirty-five healthy individuals older than 40 years of age who
      demonstrated appropriate cognition and physical stability. Specific exclusion
      criteria included any prior history of hip, knee, or ankle fracture or surgery.
      METHODS: Questionnaire regarding exercise and sun exposure, vitamin D blood
      level, followed by computerized dynamic posturography (CDP) assessment of
      balance. MAIN OUTCOME MEASUREMENTS: CDP scores of individuals with normal and
      subnormal vitamin D levels. RESULTS: Thirteen male and 22 female subjects had a
      mean age of 56.0 years (standard deviation, 7.6; range, 42-77). Self-reported,
      retrospective mean weekly sun exposure was 7.36 hours (standard deviation, 6.4
      hours). Twenty-six subjects (76.5%) described themselves as regular exercisers.
      Mean 25-OHD level for the sample was 21.5 ng/mL (standard deviation, 12.1 ng/mL).
      When subjects were divided into those with low and high 25-OHD levels, there was
      no significant difference in composite limits of stability reaction time scores
      (mean, 0.98 seconds and 0.84 seconds; P = .23), composite maximal velocity scores
      (4.2 degrees /second and 5.5 degrees /second; P = .08), composite end point
      excursion (70.3% and 70.1%; P = .95), and directional control composite scores
      (71.0% and 71.4%; P = .93). The two groups also showed no significant differences
      in rhythmic weight shifting left and right as well as forward and backward.
      CONCLUSIONS: Unlike studies involving elderly subjects, this study of younger,
      healthy subjects did not demonstrate a relationship between vitamin D and
      balance.

PMID- 20129510
TI  - Risk factors for volleyball-related shoulder pain and dysfunction.
AB  - OBJECTIVE: To identify risk factors for volleyball-related shoulder pain and
      dysfunction. DESIGN: Cross-sectional, observational. SETTING: National
      championship sporting event. PARTICIPANTS: Competitors at the 2006 National
      Intramural & Recreational Sports Association Collegiate Club Volleyball
      Championship competition were invited to volunteer for the study. A total of 422
      athletes returned questionnaires, of whom 276 also underwent a structured
      physical examination. ASSESSMENT OF RISK FACTORS: Study participants provided
      information on any history of volleyball-related shoulder pain or dysfunction.
      The simple shoulder test (SST) and a visual analog scale permitted subjects to
      quantify the extent of their perceived functional limitation. Subjects also were
      invited to undergo a physical examination in which dynamic scapular positioning,
      glenohumeral range of motion, shoulder girdle strength, and core stability were
      assessed. MAIN OUTCOME MEASUREMENTS: Standard statistical methods of comparison
      and tests of association were used to identify risk factors for shoulder pain
      among participating volleyball athletes. RESULTS: Approximately 60% of
      participants reported a history of shoulder problems. Attackers and "jump"
      servers were more likely to have shoulder problems than setters, defensive
      specialists, and "float" servers. Nearly half of the athletes who reported
      shoulder problems perceived some associated functional limitation, with female
      athletes providing lower SST scores than male athletes (9.0 versus 10.1, P =
      .001). Athletes reporting shoulder pain and dysfunction were more likely to have
      SICK scapula scores of 3 or greater (P = .010). Participants who demonstrated
      core instability also had greater SICK scapula scores (3.9 versus 2.9, P = .038),
      and were more likely to report a history of shoulder problems (chi2 = 8.83, P =
      .032). Although the authors observed a significant mean left-right difference of
      8.9 degrees in available glenohumeral internal rotation among participating
      athletes, this deficit was not associated with shoulder problems. However, there
      was an association between asymmetric coracoid tightness /pectoral shortening and
      shoulder pain (P = .030), as well as for restricted shoulder flexion in the
      sagittal plane and shoulder problems (P = .015). CONCLUSIONS: Although most risk
      factors for volleyball-related shoulder problems are similar to those identified
      for other overhead sports, there appear to be additional volleyball-specific risk
      factors that may reflect the biomechanical demands of the sport. An understanding
      of modifiable risk factors is critical to providing optimal care for overuse
      injuries and may facilitate future efforts to prevent shoulder problems among
      volleyball athletes.

PMID- 20129511
TI  - Pharmacokinetics of amantadine in children with impaired consciousness due to
      acquired brain injury: preliminary findings using a sparse-sampling technique.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of amantadine in children with
      impaired consciousness from acquired brain injury. DESIGN: Randomized, double
      blind, placebo-controlled, crossover study with sparse sampling for
      pharmacokinetics. SETTING: Tertiary care pediatric hospital. PARTICIPANTS:
      Children, ages 6-18 years, with impaired consciousness 5-10 weeks after acquired
      brain injury. METHODS: Subjects received amantadine for 3 weeks. Subjects were
      randomized to placebo or amantadine 4 mg/kg/day for 7 days followed by 6
      mg/kg/day for 14 days. Crossover was after a 7-day washout period. MAIN OUTCOME
      MEASURES: The Coma/Near-Coma Scale and Coma Recovery Scale-Revised were done 3
      times per week to evaluate arousal and consciousness. Plasma concentrations of
      amantadine were determined for pharmacokinetic parameter estimation and
      evaluation of the exposure-response relationship. Adverse events were monitored.
      RESULTS: Nine subjects met the final inclusion and exclusion criteria, 7 of whom
      agreed to participate. Five subjects completed both arms of the study. Amantadine
      total body clearance was 0.17 L/h/kg with a half-life of 13.9 hours. Higher
      exposure of amantadine (average concentration of amantadine during 6 mg/kg/day >
      1.5 mg/L) may be associated with better recovery of consciousness. CONCLUSIONS:
      Amantadine was well-tolerated in children with acquired brain injury and
      demonstrates pharmacokinetics similar to those reported for healthy young adults.
      Based on the preliminary data, higher dosing may be considered in the setting of
      brain injury.

PMID- 20129512
TI  - Health literacy among patients diagnosed with movement disorders: a pilot study.
AB  - OBJECTIVE: The study sought to examine the functional health literacy in a sample
      of geriatric patients diagnosed with movement disorders. The hypothesis was that
      the study group would demonstrate marginal levels of health literacy scores on a
      standardized health literacy instrument. DESIGN/SETTING: The study used a
      prospective analysis of patients referred to an outpatient movement disorders
      clinic in a Veterans Affairs Medical Center. PATIENTS: Fifty-four men with a
      movement disorder volunteered for the study, with data analysis conducted on 44
      of these patients. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was the
      Test of Functional Health Literacy in Adults (TOFHLA). RESULTS: Members of the
      current sample demonstrated adequate health literacy and scored significantly
      higher on the TOFHLA relative to the measure's normative sample. Younger age,
      more education, and higher Mini Mental Status Examination (MMSE) scores were
      predictive of health literacy. CONCLUSIONS: The extant literature strongly
      suggests that limited health literacy is a frequent problem across the United
      States and represents a considerable obstacle to the effective delivery of health
      care. In a group of movement disorder subjects with a Folstein MMSE of at least
      24, health literacy was generally well preserved. Years with movement disorder
      and severity of disorder did not impact health literacy. Thus, practitioners
      should not be prejudiced in a belief that individuals with movement disorders
      cannot manage their medications.

PMID- 20129513
TI  - Anatomical landmark asymmetry assessment in the lumbar spine and pelvis: a review
      of reliability.
AB  - The purpose of this article is to review current research investigating the
      reliability of bony anatomical landmark positional asymmetry assessment in the
      lumbar spine and pelvis, to determine the agreement on findings between authors,
      and to explore future directions in the area to address the significant issues.
      The databases MEDLINE, CINAHL, AMED, MANTIS, Academic Search Complete, and Web of
      Knowledge were searched. A total of 23 articles were identified and reviewed, 10
      of which met the inclusion criteria. For these 10 articles, the average
      interexaminer reliability for bony anatomical landmark positional asymmetry
      assessment was slightly above chance for all landmarks except medial malleolus,
      which had fair reliability. Interexaminer reliability on average was less than
      intraexaminer reliability (anterior superior iliac spine, k = 0.128/0.414;
      posterior superior iliac spine, k = 0.092/0.371). All interexaminer reliability
      averages were below values of clinical significance. From the current literature
      review, bony anatomical landmark positional asymmetry assessment in the lumbar
      spine and pelvis has not been demonstrated to be a reliable assessment method.
      However, there are unexplored factors that, after standardization, may improve
      reliability and further the understanding of musculoskeletal palpatory
      examination.

PMID- 20129514
TI  - The controversy surrounding central institutional review boards.

PMID- 20129515
TI  - Thoracic outlet syndrome.

PMID- 20129516
TI  - Robotic gait training in an adult with cerebral palsy: a case report.
AB  - Improved treatments and rehabilitation for cerebral palsy (CP) have led to an
      increased number of children with CP surviving into adulthood. Adults with CP
      show an increased prevalence of pain, fatigue, and musculoskeletal dysfunction,
      leading to a decrease in ambulatory function. Recent work has demonstrated the
      potential benefits of intensive task-specific gait training, including the use of
      robotic-driven gait orthoses, on motor recovery in children with CP. In contrast,
      reports of interventions aimed at improving motor function in adults with CP are
      lacking. This case study reports on the outcomes of a 6-week intervention of
      robotic-assisted gait training administered to a 52-year-old woman with right
      hemiplegia attributable to CP. Improvements were noted in balance, walking speed,
      and time to negotiate stairs at posttraining and follow-up. Gait analysis showed
      an increase in step length and a reduction in the period of double support. In
      conclusion, robotic-assisted gait training may be beneficial in enhancing
      locomotor function in adults with CP.

PMID- 20129517
TI  - Low-energy femoral fractures associated with long-term bisphosphonate use in a
      rehabilitation setting: a case series.

PMID- 20129518
TI  - Coronary CTA: stenosis classification and quantification, including automated
      measures.
AB  - The development of larger multidetector computed tomography (CT) systems has
      allowed increased accuracy in quantifying obstructive lesions involving the
      coronary arteries. This article reviews the accuracy of coronary CT angiography
      (CTA) in quantifying obstructive lesions, evaluating the extent of coronary
      artery disease, and classifying the composition of coronary plaques. In addition,
      several outcomes studies and some promising automated techniques for quantifying
      coronary CTA are reviewed.

PMID- 20129519
TI  - Trends in radiation protection in CT: present and future status.
AB  - With the introduction of modern multislice scanner generations, computed
      tomography (CT) has emerged as a useful tool for evaluation of the coronary
      arteries. A common application of coronary CT angiography (CCTA) is the
      examination of patients with intermediate pretest probability for obstructive
      coronary artery disease. Despite the widespread use of cardiac CT examinations in
      clinical practice, concern remains about the exposure to ionizing radiation and
      its potential hazards. Therefore, radiation dose and strategies for dose
      reduction have become an important focus of interest. Several smaller analyses
      have shown an effective radiation dose between 6.4 and 27.8 mSv for spiral CCTA
      image acquisition. The international Prospective Multicenter Study On RadiaTion
      Dose Estimates Of Cardiac CT AngIOgraphy I (PROTECTION I) study, the largest
      observational study on radiation dose estimates of cardiac CT so far, determined
      radiation dose estimates of CCTA, as well as the effect of different strategies
      to reduce dose in clinical practice. The median dose-length-product of 1965 CCTA
      examinations was 885 mGy x cm, which corresponds to a median estimated effective
      radiation dose of 12 mSv. However, a large variation in dose between study sites
      was observed, indicating a large potential to reduce dose for individual sites.
      Several dose-saving scanning techniques and algorithms have been developed. This
      article discusses these strategies as well as their effect on radiation dose and
      image quality. Because the contrast-enhanced CT angiography is the largest part
      of the total study dose, the following described strategies focus on radiation
      dose reduction for CCTA image acquisition.

PMID- 20129520
TI  - Clinical and technical considerations for stress myocardial perfusion imaging
      with multidetector computed tomography.
AB  - Cardiovascular compute tomography (CT) is now a robust tool for the evaluation of
      coronary artery atherosclerosis and stenosis. A number of single-center studies,
      and now multicenter trials, have shown that the diagnostic accuracy of this tool
      compares favorably with the reference standard of conventional coronary
      angiography. Of course, CT angiography does not allow for the assessment of the
      functional significance of a given coronary lesion. However, recent reports have
      shown that myocardial perfusion imaging is possible with CT, opening up the
      possibility of providing a comprehensive evaluation of both coronary anatomy and
      physiology with one examination. This article reviews the principles, technical
      considerations, and the potential of stress myocardial perfusion imaging with CT.

PMID- 20129521
TI  - Measuring progression of coronary atherosclerosis with computed tomography:
      searching for clarity among shades of gray.
AB  - Computed tomography (CT) allows visualization of both calcified and noncalcified
      atherosclerotic plaque in the entire coronary tree. When assessing an individual
      patient's risk of cardiac events, direct visualization of coronary plaque has
      substantial advantages over assessment of surrogate markers or risk factors.
      Ideally, practitioners would be able to follow progression or regression of
      coronary disease via quantitative measurements of plaque volume and composition
      in individual patients. Once this is possible, CT could be used to: (1) make more
      informed decisions about whether and how aggressively to treat patients at risk
      for coronary artery disease, and (2) to follow the effects of treatment in
      patients with known coronary artery disease. At this point in time, coronary
      calcium scoring is more reproducible than CT angiography for quantifying plaque
      and also has a much larger body of evidence supporting its ability to predict
      cardiac events. In this paper we will review the current techniques for
      quantifying calcified and noncalcified coronary atherosclerosis with cardiac CT,
      the strengths and limitations of each approach and the data supporting the
      ability to quantify and follow progression or regression of plaque.

PMID- 20129522
TI  - Methods of plaque quantification and characterization by cardiac computed
      tomography.
AB  - The pathologic evolution of coronary artery atherosclerosis occurs slowly over
      decades, which may provide an opportunity for diagnostic imaging to identify
      patients before clinical events evolve. Cardiac computed tomography (CT) is an
      emerging noninvasive imaging tool, which can visualize the entire coronary tree
      with submillimeter resolution. We reviewed the current status of cardiac CT to
      qualitatively and quantitatively determine coronary plaque dimensions and
      composition, and its potential to improve our understanding of the natural
      history of coronary artery disease as well as prevention of cardiovascular
      events.

PMID- 20129523
TI  - Efficacy of coronary CT angiography: where we are, where we are going, and where
      we want to be.
AB  - Over the decade since its earliest introduction, coronary CT angiography has
      spread rapidly, despite the fact that its validation base is smaller than that of
      alternative imaging examinations. Consensus statements have issued a call for
      improvement of coronary CT angiography's knowledge base. This article reviews
      recent progress in validating the efficacy of coronary CT angiography in the
      detection of coronary artery disease, with a focus on clinical decision making,
      management, and outcomes. We discuss the rationale for comparative effectiveness
      research and a framework for assessment of levels of efficacy. Comparison is made
      with radionuclide myocardial perfusion imaging, which serves as a model
      noninvasive examination. The potential roles of coronary CT angiography in
      screening, early triage, and as a gatekeeper for catheterization are discussed.
      Although few randomized controlled trials have been performed to date, we review
      the pivotal publications and mention ongoing and future efforts. Cardiovascular
      event rates provide the basis for estimating the success of potential study
      designs. The rigorous validation of coronary CT angiography may serve as a model
      for other noninvasive diagnostics.

PMID- 20129524
TI  - Tissue Doppler image-derived measurements during isovolumic contraction predict
      exercise capacity in patients with reduced left ventricular ejection fraction.
AB  - OBJECTIVES: We explored the incremental value of quantification of tissue Doppler
      (TD) velocity during the brief isovolumic contraction (IVC) phase of the cardiac
      cycle for the prediction of exercise performance in patients referred for
      cardiopulmonary exercise testing (CPET). BACKGROUND: Experimental studies have
      shown that rapid left ventricular (LV) shape change during IVC is essential for
      optimal onset of LV ejection. However, the incremental value of measuring IVC
      velocities in clinical settings remains unclear. METHODS: A total of 82 subjects
      (age 53+/-14 years, 56 men) were studied with echocardiography and CPET. Reduced
      LV ejection fraction (EF) (EF<50%) was present in 38 (46%) subjects. Pulsed-wave
      annular TD velocities were averaged from the LV lateral and septal annulus during
      isovolumic contraction (IVCa), ejection, isovolumic relaxation, and early and
      late diastole (Aa) and compared with peak oxygen consumption (VO2) and percentage
      of the predicted peak VO2 (% predicted peak VO2) obtained from CPET. RESULTS:
      Patients with reduced EF had lower IVCa (6.3 vs. 4.5 cm/s, p=0.04), ejection (7.7
      vs. 5.5 cm/s, p<0.001), and Aa velocities (7.9 vs. 6.6 cm/s, p=0.04). Similarly,
      % predicted peak VO2 was lower in patients with reduced EF (52.9% vs. 73.1%,
      p<0.001) and correlated with the variations in IVCa (r=0.7, p=0.001).
      Multivariate analysis of 2-dimensional and Doppler variables in the presence of
      reduced LV EF revealed only IVCa and Aa as independent predictors of % predicted
      peak VO2 (r2=0.612, p=0.02 for IVCa and p=0.009 for Aa). The overall performance
      of IVCa in the prediction of exercise capacity was good (area under the
      curve=0.86, p<0.001). CONCLUSIONS: Assessment of TD-derived IVC and atrial
      stretch velocities provide independent prediction of exercise capacity in
      patients with reduced LV EF. Assessment of LV pre-ejectional stretch and
      shortening mechanics at rest may be useful for determining the myocardial
      functional reserve of patients with reduced EF.

PMID- 20129525
TI  - Multimodality comparison of quantitative volumetric analysis of the right
      ventricle.
AB  - OBJECTIVES: We undertook volumetric analysis of the right ventricle (RV) by real
      time 3-dimensional echocardiography (RT3DE), cardiac magnetic resonance (CMR),
      and cardiac computed tomography (CCT) on images obtained in RV-shaped phantoms
      and in patients with a wide range of RV geometry. BACKGROUND: Assessment of the
      RV by 2-dimensional (2D) echocardiography remains challenging due to its unique
      geometry and limitations of the current analysis techniques. RT3DE, CMR, and CCT,
      which can quantify RV volumes, promise to overcome the limitations of 2D
      echocardiography. METHODS: Images were analyzed using RV Analysis software.
      Volumes measured in vitro were compared with the true volumes. The human protocol
      included 28 patients who underwent RT3DE, CMR, and CT on the same day. Volumetric
      analysis of CMR images was used as a reference, against which RT3DE and CCT
      measurements were compared using linear regression and Bland-Altman analyses. To
      determine the reproducibility of the volumetric analysis, repeated measurements
      were performed for all 3 imaging modalities in 11 patients. RESULTS: The in vitro
      measurements showed that: 1) volumetric analysis of CMR images yielded the most
      accurate measurements; 2) CCT measurements showed slight (4%) but consistent
      overestimation; and 3) RT3DE measurements showed small underestimation, but
      considerably wider margins of error. In humans, both RT3DE and CCT measurements
      correlated highly with the CMR reference (r=0.79 to 0.89) and showed the same
      trends of underestimation and overestimation noted in vitro. All interobserver
      and intraobserver variability values were <14%, with those of CMR being the
      highest. CONCLUSIONS: Volumetric quantification of RV volume was performed on
      CMR, CCT, and RT3DE images. Eliminating analysis-related intermodality
      differences allowed fair comparisons and highlighted the unique limitations of
      each modality. Understanding these differences promises to aid in the functional
      assessment of the RV.

PMID- 20129526
TI  - The association between plaque characterization by CT angiography and post
      procedural myocardial infarction in patients with elective stent implantation.
AB  - OBJECTIVES: This study sought to evaluate the association between volumetric
      characterization of target lesions by multidetector computed tomography (MDCT)
      angiography and the risk of post-procedural myocardial injury after elective
      stent implantation. BACKGROUND: Previous reports have shown that plaque
      characterization of the target lesion may provide useful information for
      stratifying the risk of coronary stenting. METHODS: A total of 189 consecutive
      patients were enrolled; they underwent elective stent implantation after
      volumetric plaque analysis with 64-slice MDCT. Each plaque component and lumen
      (filled with dye) was defined as follows: 1) low-attenuation plaque (LAP) (<50
      HU); 2) moderate-attenuation plaque (MAP) (50 to 150 HU); 3) lumen (151 to 500
      HU); and 4) high-attenuation plaque (HAP) (>500 HU). The volume of each plaque
      component in the target lesion was calculated using Color Code Plaque. Post
      procedural creatine kinase-MB isoform and troponin-T (TnT) at 18 h after
      percutaneous coronary intervention were also evaluated. RESULTS: The volumes of
      LAP (87.9+/-94.8 mm3 vs. 47.4+/-43.7 mm3, p<0.01) and MAP (111.6+/-77.5 mm3 vs.
      89.8+/-67.1 mm3, p<0.05) were larger in patients with post-procedural myocardial
      injury (defined as positive TnT) than in those with negative TnT. The volumes of
      LAP and MAP and fraction of LAP in total plaque (LAP volume/total plaque volume)
      correlated with biomarkers; the MAP fraction was inversely correlated with
      biomarkers. The volume of LAP was an independent predictor of positive TnT after
      adjusting for patient background, conventional IVUS parameters, and procedural
      factors. CONCLUSIONS: Post-procedural myocardial injury was associated with the
      volume and fraction of LAP as detected by MDCT. The volume of LAP was an
      independent predictor of positive TnT. Plaque analysis by MDCT would be a useful
      method for predicting post-procedural myocardial injury after percutaneous
      coronary intervention.

PMID- 20129527
TI  - Is CT the better angiogram? Coronary interventions and CT imaging.

PMID- 20129528
TI  - Segmental heterogeneity of vasa vasorum neovascularization in human coronary
      atherosclerosis.
AB  - OBJECTIVES: Our aim was to investigate the role of coronary vasa vasorum (VV)
      neovascularization in the progression and complications of human coronary
      atherosclerotic plaques. BACKGROUND: Accumulating evidence supports an important
      role of VV neovascularization in atherogenesis and lesion location determination
      in coronary artery disease. VV neovascularization can lead to intraplaque
      hemorrhage, which has been identified as a promoter of plaque progression and
      complications like plaque rupture. We hypothesized that distinctive patterns of
      VV neovascularization and associated plaque complications can be found in
      different stages of human coronary atherosclerosis. METHODS: Hearts from 15
      patients (age 52+/-5 years, mean+/-SEM) were obtained at autopsy, perfused with
      Microfil (Flow Tech, Inc., Carver, Massachusetts), and subsequently scanned with
      micro-computed tomography (CT). The 2-cm segments (n=50) were histologically
      classified as either normal (n=12), nonstenotic plaque (<50% stenosis, n=18),
      calcified (n=10) or noncalcified (n=10) stenotic plaque. Micro-CT images were
      analyzed for VV density (number/mm2), VV vascular area fraction (mm2/mm2), and VV
      endothelial surface fraction (mm2/mm3). Histological sections were stained for
      Mallory's (iron), von Kossa (calcium), and glycophorin-A (erythrocyte fragments)
      as well as endothelial nitric oxide synthase, vascular endothelial growth factor,
      and tumor necrosis factor-alpha. RESULTS: VV density was higher in segments with
      nonstenotic and noncalcified stenotic plaques as compared with normal segments
      (3.36+/-0.45, 3.72+/-1.03 vs. 1.16+/-0.21, p<0.01). In calcified stenotic
      plaques, VV spatial density was lowest (0.95+/-0.21, p<0.05 vs. nonstenotic and
      noncalcified stenotic plaque). The amount of iron and glycophorin A was
      significantly higher in nonstenotic and stenotic plaques as compared with normal
      segments, and correlated with VV density (Kendall-Tau correlation coefficient
      0.65 and 0.58, respectively, p<0.01). Moreover, relatively high amounts of iron
      and glycophorin A were found in calcified plaques. Further immunohistochemical
      characterization of VV revealed positive staining for endothelial nitric oxide
      synthase and tumor necrosis factor-alpha but not vascular endothelial growth
      factor. CONCLUSIONS: Our results support a possible role of VV
      neovascularization, VV rupture, and intraplaque hemorrhage in the progression and
      complications of human coronary atherosclerosis.

PMID- 20129529
TI  - Coronary plaque neovascularization and hemorrhage: a potential target for plaque
      stabilization?

PMID- 20129530
TI  - Myocardial salvage by CMR correlates with LV remodeling and early ST-segment
      resolution in acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to assess the association of myocardial
      salvage by cardiac magnetic resonance (CMR) with left ventricular (LV) remodeling
      and early ST-segment resolution in patients with acute myocardial infarction
      (MI). BACKGROUND: Experimental studies revealed that MI size is strongly
      influenced by the extent of the area at risk (AAR), limiting its accuracy as a
      marker of reperfusion treatment efficacy in acute MI studies. Hence, an index
      correcting MI size for AAR extent is warranted. T2-weighted CMR and delayed
      enhancement CMR, respectively, enable the determination of AAR and MI size, and
      the myocardial salvage index (MSI) is calculated by correcting MI size for AAR
      extent. Nevertheless, the clinical value of CMR-derived MSI has not been
      evaluated yet. METHODS: In a prospective cohort of 137 consecutive patients with
      acutely reperfused ST-segment elevation MI, CMR was performed at 1 week and 4
      months. T2-weighted CMR was used to quantify AAR, whereas MI size was detected by
      delayed-enhancement imaging. MSI was defined as AAR extent minus MI size divided
      by AAR extent. Adverse LV remodeling was defined as an increase in LV end
      systolic volume of >or=15%. The degree of ST-segment resolution 1 h after
      reperfusion was also calculated. RESULTS: AAR extent was consistently larger than
      MI size (32+/-15% of LV vs. 18+/-13% of LV, p<0.0001), yielding an MSI of 0.46+/
      0.24. MI size was closely related to AAR extent (r=0.81, p<0.0001). After
      correction for the main baseline characteristics by multivariate analyses, MSI
      was a major and independent determinant of adverse LV remodeling (odds ratio:
      0.64; 95% confidence interval: 0.49 to 0.84, p=0.001) and was independently
      associated with early ST-segment resolution (B coefficient=0.61, p<0.0001).
      CONCLUSIONS: In patients with reperfused ST-segment elevation MI, CMR-derived MSI
      is independently associated with adverse LV remodeling and early ST-segment
      resolution, opening new perspectives on its use in studies testing novel
      reperfusion strategies.

PMID- 20129531
TI  - Pexelizumab and infarct size in patients with acute myocardial infarction
      undergoing primary percutaneous coronary Intervention: a delayed enhancement
      cardiac magnetic resonance substudy from the APEX-AMI trial.
AB  - OBJECTIVES: The purpose of the study was to understand determinants of infarct
      size in a primary percutaneous intervention (PCI) population treated with
      pexelizumab compared with placebo. BACKGROUND: In the multicenter APEX-AMI
      (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction)
      trial, pexelizumab did not reduce 90-day mortality. Cardiac magnetic resonance
      (CMR) with delayed enhancement was used in a substudy evaluating infarct size and
      left ventricular ejection fraction (LVEF). METHODS: Consecutive patients
      undergoing primary PCI for first myocardial infarction (MI) as part of the APEX
      AMI trial were enrolled in this substudy at 5 centers. The CMR was completed on
      days 3 to 5 (n=99) and day 90 (n=83) following PCI. Central core lab-masked
      analyses for quantified LVEF, volumes, and infarct size by planimetry were
      performed. RESULTS: Patients were 60+/-12 years of age, male (n=83 [84%]), had
      similar time from symptom onset to presentation (median 2.6 h vs. 2.5 h; p=1.0),
      and similar baseline ST-segment deviation (13.5 mm vs. 14 mm; p=0.59) in both
      groups. Pexelizumab-treated patients had smaller infarct size (day 3 LV 10.5% vs.
      16.2%, p=0.022; day 90 LV 5.9% vs. 12.4%, p=0.015) and higher LVEF (day 3 50.3%
      vs. 46.2%, p=0.073; day 90 53.9% vs. 49.3%, p=0.036) compared with placebo
      treated patients. The median peak creatine kinase in the pexelizumab group was
      also significantly less than placebo (922 mg/dl vs. 1,973 mg/dl; p=0.03).
      Notably, the pexelizumab group had lower Thrombolysis In Myocardial Infarction
      (TIMI) flow grade pre-PCI (46.9% vs. 75.0%; p=0.018), a difference not seen in
      the overall APEX-AMI study. A multivariate model including baseline features and
      pexelizumab treatment found anterior MI location and pre-PCI TIMI flow to be
      significant independent predictors infarct size (p=0.001), whereas pexelizumab
      was not (p=0.29). No death, heart failure, or shock was noted in either substudy
      group at 90 days. CONCLUSIONS: In a CMR substudy of pexelizumab in MI, baseline
      TIMI flow grade and anterior location were the only predictors of infarct size,
      with a reduction of pre-PCI TIMI flow grade 0 by 28%, leading to a 35% reduction
      in infarct size. (The APEX-AMI Trial; NCT00091637).

PMID- 20129532
TI  - Myocardial infarct size reduction with pexelizumab: the role of chance is
      patently clear.

PMID- 20129533
TI  - Myocardial sympathetic innervation and long-term left ventricular mechanical
      unloading.
AB  - OBJECTIVES: The purpose of this study was to analyze the effects of left
      ventricular assist devices (LVADs) on myocardial sympathetic innervation of the
      failing heart. BACKGROUND: Ventricular unloading by LVADs seems to cause reverse
      remodeling of the failing heart, but little is known about the sympathetic nerve
      activity during long-term mechanical unloading. METHODS: We studied the effects
      of LVADs on myocardial sympathetic innervation, by iodine 123-meta
      iodobenzylguanidine (123I-mIBG) scintigraphy performed before and 3 months after
      LVAD implantation in 12 end-stage heart failure patients. We calculated the: 1)
      heart-to-mediastinum (H/M) uptake ratio on early and delayed images, indicating
      myocardial accumulation of 123I-mIBG; and 2) rate of 123I-mIBG washout after
      initial accumulation. Similar 123I-mIBG imaging and functional and hemodynamic
      measurements were made 3 months apart in 6 other heart failure patients not
      treated with an LVAD. RESULTS: After 3 months of LVAD support, the mean left
      ventricular ejection fraction had increased from 19+/-6% to 29 +/- 9% (p=0.006),
      peak oxygen consumption increased from 9+/-4 ml/kg/min to 13+/-3 ml/kg/min
      (p=0.058), serum sodium increased from 135+/-4 mEq/l to 140+/-2 mEq/l (p=0.014),
      whereas the left ventricular end-diastolic diameter decreased from 72+/-7 mm to
      56+/-3 mm (p=0.002), pulmonary capillary wedge pressure decreased from 30+/-6 mm
      Hg to 5+/-3 mm Hg (p=0.012), serum creatinine decreased from 1.5+/-0.6 mg/dl to
      1.0+/-0.4 mg/dl (p=0.011), and B-type natriuretic peptide decreased from 2,279+/
      1,900 pg/ml to 102+/-5 pg/ml (p=0.003). After 3 months of LVAD, the H/M ratio
      increased on delayed images from 1.25+/-0.18 to 1.43+/-0.13 (p=0.01) and on early
      images from 1.35+/-0.19 to 1.44+/-0.11 (p=0.028), and the washout rate decreased
      from 51.0+/-23.2% to 30.6+/-8.7%, (p=0.015). There was a significant correlation
      between the late H/M mIBG ratio and B-type natriuretic peptide (R=0.77, p=0.01)
      and systolic pulmonary pressure (R=0.7, p=0.05). No significant scintigraphic,
      functional or hemodynamic change was observed between the 2 evaluations in the 6
      patients not treated with an LVAD. CONCLUSIONS: Ventricular unloading caused
      clinical, functional, and hemodynamic improvements accompanied by improvements in
      sympathetic innervation in the failing heart.

PMID- 20129534
TI  - Adrenergic excess, hNET1 down-regulation, and compromised mIBG uptake in heart
      failure poverty in the presence of plenty.

PMID- 20129535
TI  - Accuracy of optical coherence tomography in the evaluation of neointimal coverage
      after stent implantation.
AB  - OBJECTIVES: This study aimed to evaluate the accuracy of optical coherence
      tomography (OCT) in analyzing the neointimal response to several drug-eluting
      stent (DES) types by comparing OCT images acquired in vivo with corresponding
      histological specimens using a nondiseased porcine injury model. BACKGROUND:
      Optical coherence tomography is emerging as a promising endovascular imaging tool
      for the evaluation of neointimal response after DES implantation. METHODS: A
      total of 84 stents were implanted-22 ML Vision (Abbott Vascular, Santa Clara,
      California), 22 Xience V (Abbott Vascular), 20 Endeavor (Medtronic, Minneapolis,
      Minnesota), and 20 Taxus Liberte (Boston Scientific, Natick, Massachusetts)
      stents-in normal porcine coronary arteries and were harvested at 28 (n=42) and 90
      (n=42) days, with the different stent types equally distributed between the 2
      follow-up periods. At termination, morphometric evaluation using OCT imaging was
      performed in all stented arteries. Histological morphometric analysis was
      performed and correlated with OCT. RESULTS: A total of 622 OCT-histology matched
      frames acquired from all stent designs were analyzed. The luminal (13.7%) and
      stent (6.1%) areas were consistently larger by OCT compared with histology. The
      mean neointimal thickness was very similar between techniques (approximately
      3.27% variation). There was a high correlation between OCT and histology for the
      evaluation of neointimal area (R2=0.804), luminal area (R2=0.825), and neointimal
      thickness (R2=0.789). Correlation for total stent area was poor (R2=0.352).
      Although the proportion of individual struts determined to be uncovered by OCT
      and histology was similar, there was significant variation in the estimation of
      strut coverage between OCT and histology when the neointimal thickness was
      between 20 and 80 microm. This variation converged for neointimal thicknesses
      between 80 and 100 microm. CONCLUSIONS: Subtle differences in neointimal
      formation induced by current DES can be reproducibly analyzed in vivo by OCT.
      However, OCT measurement of stent area seems to have less correlation with
      histology.

PMID- 20129536
TI  - Will intravascular OCT shed light on vascular biology?

PMID- 20129537
TI  - Assessment of percutaneous catheter treatment of paravalvular prosthetic
      regurgitation.

PMID- 20129538
TI  - Cardiac sympathetic imaging with mIBG in heart failure.
AB  - Cardiac sympathetic imaging with meta-iodobenzylguanidine (mIBG) is a noninvasive
      tool to risk stratify patients with heart failure (HF). In patients with ischemic
      and nonischemic cardiomyopathy, cardiac mIBG activity is a very powerful
      predictor of survival. Cardiac sympathetic imaging can help in understanding how
      sympathetic overactivity exerts its deleterious actions, which may result in
      better therapy and outcome for patients with HF.

PMID- 20129539
TI  - Will imaging assist in the selection of patients with heart failure for an ICD?
AB  - Sudden cardiac death remains the leading cause of death in the U.S. A left
      ventricular ejection fraction (LVEF)<30% to 35% identifies a population of
      patients at increased risk for sudden cardiac death. Once identified, an
      implantable cardioverter-defibrillator (ICD) is effective in reducing the
      occurrence of sudden cardiac death. Yet in a substantial proportion of patients
      who receive an ICD based on reduced LVEF, the device never delivers therapy.
      Furthermore, the majority of patients who die suddenly do not qualify for ICD
      placement under current LVEF-based criteria in the guidelines. This review
      considers the potential role of cardiac imaging in improving the selection of
      patients most likely to benefit from an ICD. The presence of myocardial scar
      and/or unrevascularized myocardial ischemia provides an important substrate for
      the occurrence of potentially fatal ventricular arrhythmias. The presence of
      clinical heart failure further increases the risk of ventricular arrhythmia. The
      sympathetic nervous system provides an important trigger for major arrhythmic
      events, both through global overactivity and through regional heterogeneity of
      sympathetic activity. A mismatch of myocardial perfusion and innervation may pose
      a particularly great risk. Imaging modalities provide unique opportunities to
      investigate the anatomic and pathophysiologic substrates, as well as the
      triggering effects of cardiac sympathetic innervation. Combining imaging and
      electrophysiologic modalities offers promise for improved accuracy in future
      selection of patients with heart failure for ICD placement.

PMID- 20129540
TI  - Development of mIBG as a cardiac innervation imaging agent.

PMID- 20129541
TI  - Introduction of new tests: low are the mountains, high the expectations.

PMID- 20129542
TI  - The first-generation drug-eluting stents and coronary endothelial dysfunction.
AB  - Recently, a growing body of clinical data has shown that the first generation of
      drug-eluting stents (1st-gen DES) implantation could elicit coronary conduit
      artery vasomotor dysfunction at nonstented reference segments as late as 12
      months after implantation compared with that seen with bare-metal stents. The
      mechanism of this phenomenon is still not fully understood. Pathological studies
      have implicated delayed arterial healing and poor re-endothelialization after the
      1st-gen DES implantation. Given the vast use of DES globally, a thorough
      understanding of the early and long-term safety of these devices is paramount.
      Therefore, this article systematically reviews the current clinical,
      pathophysiological, and histopathological available data regarding 1st-gen DES
      associated vascular endothelial dysfunction. Meanwhile, we will also review the
      newer generation of DES and emerging endothelial-friendly technology.

PMID- 20129543
TI  - Long-term clinical and economic analysis of the Endeavor drug-eluting stent
      versus the Driver bare-metal stent: 4-year results from the ENDEAVOR II trial
      (Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic
      AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery
      Lesions).
AB  - OBJECTIVES: This study was designed to evaluate long-term clinical and economic
      outcomes for subjects receiving Endeavor drug-eluting versus Driver bare-metal
      stents (both Medtronic CardioVascular, Santa Rosa, California). BACKGROUND: Early
      studies found that the drug-eluting stent (DES) was a clinically and economically
      attractive alternative to the bare-metal stent; however, associations between DES
      and very late stent thrombosis suggest that longer follow-up is required.
      METHODS: We used clinical, resource use and follow-up data from 1,197 subjects
      randomized to receive Endeavor (n = 598) versus Driver (n = 599) stents in
      ENDEAVOR II (Randomized Controlled Trial to Evaluate the Safety and Efficacy of
      the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native
      Coronary Artery Lesions) study with Medicare cost weights and quality of life
      adjustments applied from secondary sources. We compared differences through 4
      year follow-up (1,440 days). RESULTS: Patients in both treatment groups had
      similar baseline characteristics. The use of Endeavor versus Driver reduced 4
      year target vessel revascularization rates per 100 subjects (10.4 vs. 21.5;
      difference: -11.1; 95% confidence interval [CI]: -16.0 to -6.1; p < 0.001), with
      no difference in the rates per 100 subjects of death (5.0 vs. 5.2; difference: 
      0.2; 95% CI: -2.7 to 2.4; p = 0.90) or nonfatal myocardial infarction (3.2 vs.
      4.4; difference: -1.2; 95% CI: -3.4 to 1.0; p = 0.29). After discounting at a 3%
      annual rate, there were no differences in quality-adjusted survival days (1,093
      vs. 1,090; difference: 3; 95% CI: -13 to 19; p = 0.69) and total medical costs
      ($21,483 vs. $21,680; difference: -$198; 95% CI: -$1,608 to $1,207; p = 0.78).
      CONCLUSIONS: The use of Endeavor versus Driver was associated with a significant
      reduction in target vessel revascularization through 4-year follow-up with no
      difference in death, nonfatal myocardial infarction, quality-adjusted survival,
      or total medical costs. These results are comparable to those for other studies
      evaluating drug-eluting versus bare-metal stents. (Randomized Controlled Trial to
      Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver
      Coronary Stent in De Novo Native Coronary Artery Lesions [ENDEAVOR II];
      NCT00614848).

PMID- 20129544
TI  - Drug-eluting stents: more dollars than sense?

PMID- 20129545
TI  - 3-year clinical follow-up of the XIENCE V everolimus-eluting coronary stent
      system in the treatment of patients with de novo coronary artery lesions: the
      SPIRIT II trial (Clinical Evaluation of the Xience V Everolimus Eluting Coronary
      Stent System in the Treatment of Patients with de novo Native Coronary Artery
      Lesions).
AB  - OBJECTIVES: This paper reports the 3-year clinical outcomes of the XIENCE V
      (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES)
      compared with the TAXUS (Boston Scientific, Natick, Massachusetts) paclitaxel
      eluting stent (PES) in the randomized SPIRIT II (Clinical Evaluation of the
      Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients
      with de novo Native Coronary Artery Lesions) study. BACKGROUND: The Xience V EES
      is a new-generation drug-eluting stent (DES) that might offer advantages over the
      first-generation DES in terms of improved clinical outcomes and a better safety
      profile. METHODS: The SPIRIT II trial was a multicenter, prospective, randomized,
      single-blind, clinical trial, randomizing 300 patients with de novo coronary
      artery lesions in a ratio of 3:1 to either EES or PES. The primary end point was
      in-stent late loss at 180 days. RESULTS: At 3-year clinical follow-up cardiac
      death was numerically lower with EES than PES (0.5% vs. 4.3%, p = 0.056). The
      observed rate of myocardial infarction was 3.6% for EES and 7.2% for PES (p =
      0.31). The rate of ischemia-driven target lesion revascularization was 4.6% and
      10.1% for EES and PES, respectively (p = 0.14). Overall, there was a trend for
      lower major adverse cardiovascular events in the EES group compared with PES
      (7.2% vs. 15.9%, p = 0.053). The rate of stent thrombosis was low and comparable
      in both groups (EES 1.0% vs. PES 2.9%). CONCLUSIONS: The present study reports
      the favorable 3-year clinical outcomes of the EES, which are consistent with the
      results from other studies of the EES with shorter follow-up.

PMID- 20129546
TI  - Long-term clinical and economic analysis of the Endeavor zotarolimus-eluting
      stent versus the cypher sirolimus-eluting stent: 3-year results from the ENDEAVOR
      III trial (Randomized Controlled Trial of the Medtronic Endeavor Drug [ABT-578]
      Eluting Coronary Stent System Versus the Cypher Sirolimus-Eluting Coronary Stent
      System in De Novo Native Coronary Artery Lesions).
AB  - OBJECTIVES: The aim of this study was to evaluate clinical and economic outcomes
      for subjects receiving zotarolimus-eluting (ZES) (n = 323) versus sirolimus
      eluting stents (SES) (n = 113) in the ENDEAVOR III (Randomized Controlled Trial
      of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the
      Cypher Sirolimus-Eluting Coronary Stent System in De Novo Native Coronary Artery
      Lesions) clinical trial. BACKGROUND: Although previous clinical trials have
      evaluated long-term clinical outcome for drug-eluting stents, none considered
      their economic implications. METHODS: We analyzed case report form information
      with quality-of-life adjustment and Medicare cost weights applied from secondary
      sources; compared differences in clinical outcomes, quality-adjusted survival,
      medical resource use, and medical costs; and evaluated cost-effectiveness through
      3-year follow-up. RESULTS: The use of ZES versus SES reduced the 3-year rates/100
      subjects of death or myocardial infarction (3.9 vs. 10.8; difference, -6.9; 95%
      confidence interval [CI]: -13.0 to 0.8; p = 0.028), with no difference in target
      vessel revascularization rates (17.9 vs. 12.2; difference, 5.7; 95% CI: -3.7 to
      15.1; p = 0.23) but greater use of coronary artery bypass graft (CABG) surgery
      (3.5 vs. 0.0; difference 3.5; 95% CI: 1.3 to 5.7; p = 0.002). After discounting
      at 3% per annum, total medical costs for ZES versus SES were similar ($23,353 vs.
      $21,657; difference, $1,696; 95% CI: -$1,089 to $4,482, p = 0.23), and the 3-year
      cost-effectiveness ratio was $57,002/quality-adjusted life year. CONCLUSIONS:
      Despite a reduction in death or myocardial infarction and no difference in total
      revascularizations, medical costs were not decreased due to increased CABG repeat
      revascularization procedures for subjects receiving ZES versus SES. If future
      trials observe similar differences, improved safety with no difference in medical
      costs, the use of ZES versus SES will be a clinically and economically attractive
      treatment strategy. (The Medtronic Endeavor III Drug Eluting Coronary Stent
      System Clinical Trial [ENDEAVOR III]; NCT00217256).

PMID- 20129547
TI  - Late safety, efficacy, and cost-effectiveness of a zotarolimus-eluting stent
      compared with a paclitaxel-eluting stent in patients with de novo coronary
      lesions: 2-year follow-up from the ENDEAVOR IV trial (Randomized, Controlled
      Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System
      Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native
      Coronary Artery Lesions).
AB  - OBJECTIVES: The aim of this study was to assess, after 2 years of follow-up, the
      safety, efficacy, and cost-effectiveness of a zotarolimus-eluting stent (ZES)
      compared with a paclitaxel-eluting stent (PES) in patients with native coronary
      lesions. BACKGROUND: Early drug-eluting stents were associated with a small but
      significant incidence of very late stent thrombosis (VLST), occurring >1 year
      after the index procedure. The ZES has shown encouraging results in clinical
      trials. METHODS: The ENDEAVOR IV trial (Randomized, Controlled Trial of the
      Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus
      Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery
      Lesions), a randomized (1:1), single-blind, controlled trial (n = 1,548) compared
      ZES versus PES in patients with single de novo coronary lesions. Two-year follow
      up was obtained in 96.0% of ZES and 95.4% of PES patients. The primary end point
      was target vessel failure (TVF), and safety end points included Academic Research
      Consortium-defined stent thrombosis. Economic end points analyzed included
      quality-adjusted survival, medical costs, and relative cost-effectiveness of ZES
      and PES. RESULTS: The TVF at 2 years was similar in ZES and PES patients (11.1%
      vs. 13.1%, p = 0.232). There were fewer myocardial infarctions (MIs) in ZES
      patients (p = 0.022), due to fewer periprocedural non-Q-wave MIs and fewer late
      MIs between 1 and 2 years. Late MIs were associated with increased VLST (PES: 6
      vs. ZES: 1; p = 0.069). Target lesion revascularization was similar comparing ZES
      with PES (5.9% vs. 4.6%; p = 0.295), especially in patients without planned
      angiographic follow-up (5.2% vs. 4.9%; p = 0.896). The cost-effectiveness of ZES
      and PES was similar. CONCLUSIONS: After 2 years of follow-up, ZES demonstrated
      efficacy and cost-effectiveness comparable to PES, with fewer MIs and a trend
      toward less VLST. (The ENDEAVOR IV Clinical Trial: A Trial of a Coronary Stent
      System in Coronary Artery Lesions; NCT00217269).

PMID- 20129548
TI  - Clinical outcomes after unrestricted implantation of everolimus-eluting stents.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of
      unrestricted everolimus-eluting stent (EES) implantation in a contemporary cohort
      of real-world patients. BACKGROUND: The randomized SPIRIT (A Clinical Evaluation
      of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of
      Patients With de Novo Native Coronary Artery Lesions) trials have evaluated the
      performance of EES, resulting in their approval by the Food and Drug
      Administration, but data regarding unselected usage, including off-label
      indications are lacking. METHODS: Consecutive patients treated with EES (either
      PROMUS, Boston Scientific Corp., Natick, Massachusetts, or XIENCE-V, Abbott
      Vascular Devices, Santa Clara, California) between October 2006 and February 2008
      were analyzed. End points were cardiac death, myocardial infarction (MI),
      ischemic-driven target lesion revascularization (TLR), stent thrombosis (ST), and
      major adverse cardiac events (MACE) (a composite of cardiac death, MI, TLR)
      during follow-up. RESULTS: We identified 345 patients (573 lesions) treated with
      EES. The majority of patients (71.9%) were treated for > or =1 off-label or
      untested indication. Clinical follow-up was completed in 99%. At a median follow
      up of 378 days (interquartile range 334 to 473), MACE occurred in 36 (10.6%)
      patients, TLR in 27 (7.9%), MI in 7 (2.1%), and cardiac death in 7 (2.1%).
      Definite and probable ST was observed in 3 (0.9%) cases. Off-label EES
      implantation was not associated with a statistically significant increased risk
      of MACE (12.2% vs. 6.3%, p = 0.17), TLR (9.3% vs. 4.2%, p = 0.18), or ST (0.8%
      vs. 1.1%, p = 1.0). On multivariable analysis, previous bypass surgery (p =
      0.002) and diabetes (p = 0.03) were associated with MACE. CONCLUSIONS: In
      unrestricted daily practice, EES were implanted predominantly for off-label
      indications and associated with a relative low rate of MACE and TLR.

PMID- 20129549
TI  - Safety and effectiveness of the Endeavor zotarolimus-eluting stent in real-world
      clinical practice: 12-month data from the E-Five registry.
AB  - OBJECTIVES: The E-Five registry was designed to evaluate the safety and
      effectiveness of the Endeavor zotarolimus-eluting stent (ZES) (Medtronic
      CardioVascular, Santa Rosa, California) for the treatment of coronary artery
      stenosis across a wide range of patients treated in real-world clinical practice
      settings. BACKGROUND: Early clinical trials with the Endeavor ZES have
      demonstrated low rates of target lesion revascularization with a favorable safety
      profile including low late stent thrombosis with up to 4 years of follow-up. A
      clinical registry was designed to complement controlled trial data by examining a
      large patient population, including high-risk patient subsets. METHODS: The E
      Five registry is a prospective, nonrandomized, multicenter global registry
      conducted at 188 centers worldwide. Adult patients (n = 8,314) with coronary
      artery disease who underwent single-vessel or multivessel percutaneous coronary
      intervention were enrolled. The primary end point was the rate of major adverse
      cardiac events (MACE) at 12 months. A secondary analysis stratified patients by
      standard versus extended-use clinical and lesion characteristics. RESULTS:
      Overall 12-month outcome rates were MACE 7.5%; cardiac death 1.7%; myocardial
      infarction (all) 1.6%; target lesion revascularization 4.5%; and stent thrombosis
      (Academic Research Consortium definite and probable) 1.1%. The 12-month MACE
      rates were 4.3% and 8.6% for standard- and extended-use patients, respectively (p
      < 0.001). CONCLUSIONS: This large, international multicenter registry provides
      important information regarding the long-term safety and efficacy of the Endeavor
      ZES across standard and extended-use patients in the real-world setting. Rates of
      MACE and measures of safety including cardiac death, myocardial infarction, and
      stent thrombosis were low and consistent with pooled results of clinical trials.
      (E-Five Registry: A World-Wide Registry With The Endeavor Zotarolimus Eluting
      Coronary Stent [eFive Registry]; NCT00623441).

PMID- 20129550
TI  - Second-generation drug-eluting stents and the continuous need for rapidly
      available real-world data.

PMID- 20129551
TI  - Evaluation in 3 months duration of neointimal coverage after zotarolimus-eluting
      stent implantation by optical coherence tomography: the ENDEAVOR OCT trial.
AB  - OBJECTIVES: We performed this study to investigate the vascular response in early
      period after zotarolimus-eluting stent (ZES) (Endeavor Sprint, Medtronic
      CardioVascular, Minneapolis, Minnesota) implantation. BACKGROUND: The ZES has
      different characteristics, with biocompatible polymer and rapid drug-elution,
      compared with the first-generation drug-eluting stents (DES). METHODS: The
      ENDEAVOR OCT (Evaluation in 3 Months Duration of Neointimal Coverage after
      Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography) trial is
      a prospective, single-center study evaluating vascular healing patterns with
      optical coherence tomography (OCT) at 3 months after stent implantation. A total
      of 31 ZES in 30 patients underwent serial OCT at immediate post-intervention and
      3 months. Neointimal growth and malapposition were analyzed at each stent strut
      of cross-sectional OCT images with 0.5-mm intervals. RESULTS: The incidence of
      malapposition at post-intervention and 3 months was 6.0% and 0.2%, respectively.
      However, late acquired malapposition was not detected at 3 months. Of 31 stents,
      27 stents (87.1%) were covered completely with neointima, but the remaining 4
      stents had 2 (0.8%), 4 (0.9%), 4 (1.2%), and 6 (1.4%) uncovered struts. Overall
      mean percentage of covered stent struts was 99.9 +/- 0.4%. This finding was
      consistent among groups with acute coronary syndrome and stable angina pectoris
      (99.9 +/- 0.3% vs. 99.9 +/- 0.4%, p = 0.92). Intracoronary thrombus was
      documented in 1 stent (3.2%) among 31 stents. CONCLUSIONS: Most of the stent
      struts were covered with neointima, and late acquired malapposition was not found
      at 3 months after ZES implantation. Therefore, the current study demonstrated
      that ZES might have a favorable in vivo vascular response at 3 months after stent
      implantation. (Evaluation of Zotarolimus Eluting Stent at 3 Months Using Optical
      Coherence Tomography [ENDEAVOR OCT]; NCT00815139).

PMID- 20129552
TI  - Long-term safety and efficacy with paclitaxel-eluting stents: 5-year final
      results of the TAXUS IV clinical trial (TAXUS IV-SR: Treatment of De Novo
      Coronary Disease Using a Single Paclitaxel-Eluting Stent).
AB  - OBJECTIVES: The pivotal TAXUS IV (TAXUS IV-SR: Treatment of De Novo Coronary
      Disease Using a Single Paclitaxel-Eluting Stent) trial evaluated the long-term
      safety and effectiveness of the paclitaxel-eluting stent (PES) compared with an
      otherwise identical bare-metal stent (BMS) in a relatively uncomplicated
      population of patients with a single de novo lesion in a native coronary vessel,
      treated between March and July 2002. BACKGROUND: Long-term follow-up is required
      to determine whether the early safety and efficacy of drug-eluting stents are
      maintained. METHODS: The primary end point of this prospective, randomized,
      double-blind trial was 9-month ischemia-driven target vessel revascularization
      (TVR) for PES versus the BMS control. Follow-up was complete in 1,230 (95.1%) of
      1,294 randomized evaluable patients at 5 years. RESULTS: Compared with BMS, PES
      significantly reduced TVR at 9 months (12.1% vs. 4.7%; p < 0.0001); this benefit
      was maintained through 5 years (27.4% vs. 16.9%; p < 0.0001), given comparable
      TVR rates for BMS and PES between years 1 and 5 (4.1%/year vs. 3.3%/year;
      respectively, p = 0.16). Similar patterns were observed for composite major
      adverse cardiac events (MACE) (32.8% BMS vs. 24.0% PES, p = 0.0001 at 5 years).
      Stent thrombosis was comparable for PES and BMS at 9 months (0.8% BMS vs. 0.8%
      PES; p = 0.98) and at 5 years (2.1% BMS vs. 2.2% PES, p = 0.87). The overall
      revascularization benefits of PES were consistent across multiple subgroups,
      including sex, diabetes, left anterior descending artery lesion location,
      reference vessel diameter, lesion length, and multiple stents. CONCLUSIONS: These
      5-year results demonstrate the long-term safety and sustained efficacy of PES
      compared with BMS in patients with noncomplex lesions. (TAXUS IV-SR: Treatment of
      De Novo Coronary Disease Using a Single Paclitaxel-Eluting Stent; NCT00292474).

PMID- 20129553
TI  - 3-year clinical outcome of patients with chronic total occlusion treated with
      drug-eluting stents.
AB  - OBJECTIVES: The aim of this study was to evaluate whether percutaneous coronary
      intervention (PCI) with drug-eluting stent (DES) reduces major adverse cardiac
      events (MACE) in patients with chronic coronary total occlusions (CTO) compared
      with bare-metal stent (BMS) during 3-year follow-up. BACKGROUND: The long-term
      prognosis of patients with CTO treated with PCI and DES implantation is poorly
      investigated. METHODS: We compared the 3-year clinical outcome of 124 patients
      with CTO after successful PCI with DES implantation with that of 159 patients
      with CTO previously treated with BMS. MACE were defined as death, myocardial
      infarction, and target lesion revascularization (repeat PCI or coronary artery
      bypass surgery) and were considered as combined primary end point. RESULTS: After
      3 years, the composite end point was significantly lower in the DES than in the
      BMS group: 18% versus 28%, respectively, (p < 0.05). The difference was due to
      the reduction of target lesion revascularization with DES compared with BMS-8%
      versus 21%, respectively, (p < 0.004). The Cox proportional hazards model
      identified: DES versus BMS (adjusted hazard ratio [HR]: 0.338, 95% confidence
      interval [CI]: 0.19 to 0.60, p = 0.0001), lesion length (HR: 1.033, 95% CI: 1.008
      to 1.058, p = 0.012), and final minimal lumen diameter (HR: 0.456, 95% CI: 0.232
      to 0.898, p = 0.023) as independent predictors of MACE at 3-year follow-up.
      CONCLUSIONS: After 3 years, DES were superior to BMS in reducing MACE in patients
      with CTO and should be considered the preferred treatment strategy.

PMID- 20129554
TI  - Gone but not forgotten: the case for drug-eluting stents in percutaneous
      revascularization of the chronic coronary total occlusion.

PMID- 20129556
TI  - Stent expansion as a mechanical parameter to predict late stent patency: back to
      the basics.

PMID- 20129555
TI  - Impact of post-intervention minimal stent area on 9-month follow-up patency of
      paclitaxel-eluting stents: an integrated intravascular ultrasound analysis from
      the TAXUS IV, V, and VI and TAXUS ATLAS Workhorse, Long Lesion, and Direct Stent
      Trials.
AB  - OBJECTIVES: We investigated the predictive value of the intravascular ultrasound
      (IVUS) measured post-intervention minimum stent area (MSA) on 9-month follow-up
      paclitaxel-eluting stent (PES) patency compared with bare-metal stents (BMS).
      BACKGROUND: Stent underexpansion is a strong predictor for restenosis after
      sirolimus-eluting stent implantation, but the implication of underexpansion in
      PES is still unknown. METHODS: From the combined TAXUS IV, V, and VI and TAXUS
      ATLAS Workhorse, Long Lesion, and Direct Stent trials, 1,580 patients (PES 1,098,
      BMS 482) in IVUS substudies were analyzed. The MSA that best predicted
      angiographic in-stent restenosis (ISR) (% diameter stenosis > or =50%) was
      determined. RESULTS: The post-intervention IVUS MSA was similar in PES and BMS
      (6.6 +/- 2.5 mm(2) vs. 6.7 +/- 2.3 mm(2), p = 0.92). At 9-month follow-up, ISR
      was lower in the PES group versus the BMS group (10% vs. 31%, p < 0.0001). Using
      multivariable logistic regression analysis, post-intervention IVUS MSA was the
      independent predictor of subsequent ISR in both the PES and BMS groups (p =
      0.0002 for PES and p = 0.0002 for BMS). The ability of the post-intervention IVUS
      MSA to predict ISR was further assessed using receiver operating characteristic
      analysis. The post-intervention IVUS MSA was found to be a faithful discriminator
      between patients with and without ISR in both PES (c = 0.6382) and BMS (c =
      0.6373). Finally, the optimal thresholds of post-intervention IVUS MSA that best
      predicted stent patency at 9 months were 5.7 mm(2) for PES and 6.4 mm(2) for BMS.
      CONCLUSIONS: Post-intervention MSA measured by IVUS can predict 9-month follow-up
      stent patency after both PES and BMS implantation. (Randomized Trial Evaluating
      Slow-Release Formulation TAXUS Paclitaxel-Eluting Coronary Stents to Treat De
      Novo Coronary Lesions; NCT00301522) (Direct Stenting of TAXUS Liberte-SR Stent
      for the Treatment of Patients With de Novo Coronary Artery Lesions; NCT00371423)
      (A Study of the TAXUS Liberte Stent for the Treatment of Long De Novo Coronary
      Artery Lesions; NCT00371475) (A Study of the TAXUS Liberte Stent for the
      Treatment of de Novo Coronary Artery Lesions in Small Vessels; NCT00371748).

PMID- 20129557
TI  - Identifying the "optimal" duration of dual antiplatelet therapy after drug
      eluting stent revascularization.
AB  - Uncertainty regarding the appropriate duration of dual antiplatelet therapy
      (DAPT) with aspirin and a thienopyridine challenges every clinician involved in
      the care of patients considered for or treated with drug-eluting stents (DES).
      Despite guideline recommendations for extended (> or =12 months) DAPT following
      percutaneous coronary revascularization with DES, few data are available to guide
      clinical decision-making beyond consensus opinion. Yet considering the clinical
      implications of stent thrombosis (ST) and its unpredictability in late occurring
      events, comprehensive assessment of the relationship between DAPT duration and ST
      over the long-term is a focus for DES-related clinical trials and an essential
      public health measure. Despite the potential for prolonged DAPT to reduce late
      term cardiovascular events related to the progression of atherosclerosis, few
      studies have formally examined the safety and efficacy of extended DAPT and its
      impact on late ST events. The purpose of this paper is to appraise the existing
      evidence regarding the relationship between long-term DAPT and late
      cardiovascular events; address outstanding (and unstudied) dilemmas related to
      DAPT in DES-treated patients; and propose considerations for both trial design
      and clinical practice.

PMID- 20129558
TI  - Two cases of coronary stent thrombosis very late after bare-metal stenting.

PMID- 20129559
TI  - Progression of late stent malapposition beyond 2 years after sirolimus-eluting
      stent implantation.

PMID- 20129560
TI  - Guidelines: when the doctor becomes the patient things never seem to fit.

PMID- 20129561
TI  - Catheter interventions for hemodialysis fistulas and grafts.
AB  - More than 1 in 1,000 patients in the U.S. has end-stage renal disease, and most
      patients who require renal-replacement therapy undergo hemodialysis. By the year
      2020, more than 750,000 patients are expected to have end-stage renal disease,
      and over 500,000 will require hemodialysis. The greatest limitation of
      hemodialysis is the finite durability of hemodialysis accesses, which on average
      remain patent for <3 years but are the lifeline for hemodialysis patients.
      Catheter-based interventions are successful in restoring flow in more than 80% of
      hemodialysis accesses that undergo thrombosis and have replaced surgical revision
      as the treatment of choice for failing or thrombosed accesses. Catheter-based
      interventions have improved the quality of life for hemodialysis patients by
      reducing the need for temporary hemodialysis catheters and have prolonged total
      survival time by preserving existing access sites and by saving venous segments
      for future access creation. This review discusses the pathophysiology of dialysis
      access failure, presents the success rates of catheter-based treatments, and
      illustrates the interventional approaches for treating failing and thrombosed
      fistulas and grafts.

PMID- 20129562
TI  - Incidence and predictors of very late (>or=4 years) major cardiac adverse events
      in the DESIRE (Drug-Eluting Stents in the Real World)-Late registry.
AB  - OBJECTIVES: Our aim was to access the incidence of late major adverse cardiac
      events (MACE) and stent thrombosis (ST) in nonselected, complex patients followed
      for a period >/=4 years. BACKGROUND: Despite the efficacy of drug-eluting stents
      (DES) in reducing repeated target lesion revascularization, concerns regarding
      the occurrence of late and very late ST have partially obscured the benefits of
      this novel technology. METHODS: All consecutive patients treated solely with DES
      between May 2002 and January 2005 were enrolled into this prospective,
      nonrandomized, single-center registry. The primary end point was long-term
      occurrence of MACE up to 7 years. Independent predictors of MACE, cardiac death,
      target lesion revascularization, and ST were obtained by a multivariate Cox
      proportional hazards regression model. RESULTS: A total of 1,010 patients were
      enrolled. Most of them were men (77%) with a mean age of 63.7 years.
      Stent/patient rate was 1.4. Patients were kept in dual antiplatelet therapy for 3
      and 6 months after Cypher (Cordis, Johnson & Johnson, Miami Lakes, Florida) and
      Taxus (Boston Scientific Corp., Natick, Massachusetts) stent implantation,
      respectively. Follow-up was obtained in 98.2% of the cohort (median 5.01 years).
      Survival free of MACE and cumulative incidence of definite/probable ST were 84.6%
      and 1.7%, respectively. Independent predictors of ST were percutaneous coronary
      intervention in the setting of acute myocardial infarction, DES overlapping,
      treatment of multivessel disease, presence of moderate-to-severe calcification at
      lesion site, and in-stent residual stenosis. CONCLUSIONS: The deployment of DES
      in complex, real-world patients resulted in a low rate of very long-term MACE and
      ST. However, ST still occurs very long after the index procedure.

PMID- 20129563
TI  - The DESIRE-Late registry: what is left to be desired?

PMID- 20129564
TI  - Culprit vessel percutaneous coronary intervention versus multivessel and staged
      percutaneous coronary intervention for ST-segment elevation myocardial infarction
      patients with multivessel disease.
AB  - OBJECTIVES: The purpose of this study was to examine the differences in in
      hospital and longer-term mortality for ST-segment elevation myocardial infarction
      (STEMI) patients with multivessel disease as a function of whether they underwent
      single-vessel (culprit vessel) percutaneous coronary interventions (PCIs) or
      multivessel PCI. BACKGROUND: The optimal treatment of patients with STEMI and
      multivessel disease is of continuing interest in the era of drug-eluting stents.
      METHODS: STEMI patients with multivessel disease undergoing PCIs in New York
      between January 1, 2003, and June 30, 2006, were subdivided into those who
      underwent culprit vessel PCI and those who underwent multivessel PCI during the
      index procedure, during the index admission, or staged within 60 days of the
      index admission. Patients were propensity-matched and mortality rates were
      calculated at 12, 24, and 42 months. RESULTS: A total of 3,521 patients (87.5%)
      underwent culprit vessel PCI during the index procedure. A total of 259 of them
      underwent staged PCI during the index admission and 538 patients underwent staged
      PCI within 60 days of the index procedure. For patients without hemodynamic
      compromise, culprit vessel PCI during the index procedure was associated with
      lower in-hospital mortality than multivessel PCI during the index procedure (0.9%
      vs. 2.4%, p = 0.04). Patients undergoing staged multivessel PCI within 60 days
      after the index procedure had a significantly lower 12-month mortality rate than
      patients undergoing culprit vessel PCI only (1.3% vs. 3.3%, p = 0.04).
      CONCLUSIONS: Our findings support the American College of Cardiology/American
      Heart Association (ACC/AHA) recommendation that culprit vessel PCI be used for
      STEMI patients with multivessel disease at the time of the index PCI when
      patients are not hemodynamically compromised. However, staged PCI within 60 days
      after the index procedure, including during the index admission, is associated
      with risk-adjusted mortality rates that are comparable with the rate for culprit
      vessel PCI alone.

PMID- 20129565
TI  - Multivessel intervention during primary angioplasty: too greedy?

PMID- 20129566
TI  - High residual platelet reactivity after clopidogrel: extent of coronary
      atherosclerosis and periprocedural myocardial infarction in patients with stable
      angina undergoing percutaneous coronary intervention.
AB  - OBJECTIVES: We tested the hypothesis that residual platelet reactivity after
      clopidogrel correlates with the extent and severity of coronary atherosclerosis
      in patients undergoing elective percutaneous coronary intervention (PCI).
      BACKGROUND: Platelets are actively involved in vascular atherosclerosis. METHODS:
      We prospectively enrolled 338 patients undergoing PCI for stable angina, loaded
      with 600-mg clopidogrel. Platelet reactivity was assessed 12 h later by measuring
      P2Y12 reactivity unit (PRU) with VerifyNow P2Y12 assay (Accumetrics, San Diego,
      California). High platelet reactivity (HPR) was defined as PRU value >or=240.
      Presence of multivessel disease (MVD) and total stent length (TSL) were used as
      surrogate markers of atherosclerosis severity and extension. RESULTS: Patients
      with MVD showed higher PRU compared with single-vessel disease (SVD) patients
      (222 +/- 85 vs. 191 +/- 73; p < 0.001). The PRU increased with the number of
      stenotic coronaries (1-vessel disease: 191 +/- 73; 2-vessel disease: 220 +/- 88;
      3-vessel disease: 226 +/- 80; p = 0.002). The PRU was higher in the third TSL
      tertile compared with first tertile (217 +/- 83 vs. 191 +/- 73; p = 0.048). The
      HPR was most frequently observed among MVD patients (40.5% vs. 21.6% in patients
      with SVD, respectively; p < 0.001) and those in the third TSL tertile (35.8% vs.
      22.2% first tertile; p = 0.028). Higher incidence of periprocedural myocardial
      infarction was observed in patients with HPR (41.2% vs. 26.7% in patients without
      HPR; p = 0.008) and in those in the third tertile TSL (37.7% vs. 23.1% first
      tertile; p = 0.020). By multivariate analysis, HPR was the only independent
      predictor of periprocedural myocardial infarction (p = 0.034). CONCLUSIONS:
      Patients with more extensive coronary atherosclerosis have a higher rate of HPR,
      which might partly account for higher risk of periprocedural MI.

PMID- 20129567
TI  - 3-Dimensional bifurcation angle analysis in patients with left main disease: a
      substudy of the SYNTAX trial (SYNergy Between Percutaneous Coronary Intervention
      with TAXus and Cardiac Surgery).
AB  - OBJECTIVES: We explore the bifurcation angle (BA) parameters of the left main
      coronary artery (LM), the effect of percutaneous coronary intervention (PCI) on
      this angulation, and the impact of BA on clinical outcome. BACKGROUND: The BA is
      emerging as a predictor of outcome after PCI of bifurcation lesions. Three
      dimensional (3D) quantitative coronary angiography (QCA) overcomes the
      shortcomings of 2-dimensional analysis and provides reliable data. METHODS: This
      is a substudy of the SYNTAX (SYNergy Between Percutaneous Coronary Intervention
      With TAXus and Cardiac Surgery) trial. The cineangiograms of the 354 patients who
      underwent PCI of their LM stem were analyzed with 3D QCA software (CardiOp-B,
      Paieon Medical, Ltd., Rosh Ha'ayin, Israel). The proximal BA (between LM and left
      circumflex [LCX]) and the distal BA (between left anterior descending and LCX)
      were computed in end-diastole and end-systole, both before and after PCI. The
      cumulative major adverse cardiac and cardiovascular event (MACCE) rates
      throughout the 12-month period after randomization were stratified across pre-PCI
      distal BA values and compared accordingly. RESULTS: Complete analysis was
      feasible in 266 (75.1%) patients. Proximal and distal BA had mean pre-PCI end
      diastolic values of 105.9 +/- 21.7 degrees and 95.6 +/- 23.6 degrees ,
      respectively, and were inversely correlated (r = -0.75, p < 0.001). During
      systolic motion of the heart there was an enlargement of the proximal angle and a
      reduction of the distal angle (DeltaBA -8.2 degrees and 8.5 degrees ,
      respectively, p < 0.001 for both). The PCI resulted in a mean decrease in the
      distal BA (DeltaBA 4.5 degrees , p < 0.001). The MACCE rates did not differ
      across distal BA values; freedom from MACCE at 12 months was 82.8%, 85.4%, and
      81.1% (p = 0.74) for diastolic values (first through third tertile). CONCLUSIONS:
      Left main BA analysis with 3D QCA is feasible. Both proximal and distal angles
      are affected by cardiac motion; PCI modifies the distal angle. There is no clear
      difference in event rates across pre-PCI distal BA values.

PMID- 20129568
TI  - Cardioprotective role of remote ischemic periconditioning in primary percutaneous
      coronary intervention: enhancement by opioid action.
AB  - OBJECTIVES: We sought to determine the potential of remote ischemic
      periconditioning (RIPC), and its combination with morphine, to reduce reperfusion
      injury in primary percutaneous coronary interventions. BACKGROUND: Remote
      ischemic post-conditioning is implemented by applying cycles of ischemia and
      reperfusion on a remote organ, which result in release of circulating factors
      inducing the effects of post-conditioning on the myocardium. METHODS: A total of
      96 patients (59 men) were enrolled. The patients were randomized to groups as
      follows: 33 to each treatment group (Group A: RIPC; Group B: RIPC and morphine)
      and 30 to the control group (Group C). Measures of efficacy were achievement of
      full ST-segment resolution (primary), and reduction of ST-segment deviation score
      and peak troponin I during hospitalization. RESULTS: A higher proportion of
      patients in Groups A (73%) and B (82%) achieved full ST-segment resolution after
      percutaneous coronary intervention, compared with control patients (53%) (p =
      0.045). Peak troponin I was lowest in Group B, 103.3 +/- 13.3 ng/ml, in
      comparison to peak levels in Group A, 166.0 +/- 28.0 ng/ml, and the control
      group, 255.5 +/- 35.5 ng/ml (p = 0.0006). ST-segment deviation resolution was
      87.3 +/- 2.7% in Group B, compared with 69.9 +/- 5.1% in Group A and 53.2 +/-
      6.4% in the control group (p = 0.00002). In paired comparisons between groups,
      Group B did better than the control group in terms of both ST-segment reduction
      (p = 0.0001) and peak troponin I (p = 0.004), whereas Group A differences from
      the control group did not achieve statistical significance (p = 0.054 and p =
      0.062, respectively). CONCLUSIONS: These findings demonstrate a cardioprotective
      effect of RIPC and morphine during primary percutaneous coronary intervention for
      the prevention of reperfusion injury. This is in agreement with observations that
      the beneficial effect of RIPC is inhibited by the opioid receptor blocker
      naloxone.

PMID- 20129569
TI  - Post-conditioning for cardioprotection during reperfusion therapy: too good to be
      true?

PMID- 20129570
TI  - First clinical experience of "flower petal stenting": a novel technique for the
      treatment of coronary bifurcation lesions.
AB  - OBJECTIVES: We sought to report the results of both bench-testing and our first
      clinical experience with this novel technique. BACKGROUND: The optimal stenting
      technique for bifurcation lesions has yet to be defined. METHODS: This technique
      works by flaring the proximal side of the stent in side branch out like a flower
      petal. We tested it in vitro and the resultant stent structure and stent polymer
      damage was observed in both main branch and side branch with an optical
      microscopy, multislice computer tomography, intravascular ultrasound, endoscopy,
      and by electron microscopy. We also applied this technique in 33 patients and
      assessed patient outcomes up to 9 months prospectively. Drug-eluting stents were
      used for the bench tests and for all patients. RESULTS: Bench-testing showed
      complete coverage of the bifurcation with minimal stent-layer overlapping. There
      was little polymer damage by electron microscopy. Procedural success was achieved
      in all cases and restenosis occurred in 2 cases. In both restenosis cases,
      "petal" stenting technique was done reluctantly after another stent had already
      been deployed in the main branch before any stenting of the side branch. There
      were no incidences of restenosis when this technique was used electively.
      CONCLUSIONS: In terms of damage to the polymer and ostial strut coverage, this
      new "flower petal stenting" technique is effective for treatment of bifurcation
      lesion and it may well be superior to other available techniques.

PMID- 20129571
TI  - The artisan approach for stenting bifurcation lesions.

PMID- 20129572
TI  - Anti-CD34 antibodies immobilized on the surface of sirolimus-eluting stents
      enhance stent endothelialization.
AB  - OBJECTIVES: In this study, we hypothesized that an antihuman-CD34 antibody
      immobilized on the surface of commercially available sirolimus-eluting stents
      (SES) could enhance re-endothelialization compared with SES alone. BACKGROUND:
      Previous experience with antihuman-CD34 antibody surface modified Genous stents
      (GS) (OrbusNeich Medical, Fort Lauderdale, Florida) has shown enhanced stent
      endothelialization in vivo. METHODS: In the phase 1 study, stents were deployed
      in 21 pig coronary arteries for single stenting (9 vessels: 3 GS, 3 SES, and 3
      bare-metal stents) and overlapping stenting with various combinations (12
      vessels: 4 GS+GS, 4 SES+SES, and 4 GS+SES) and harvested at 14 days for scanning
      electron and confocal microscopy. In phase 2, immobilized anti-CD34 antibody
      coating was applied on commercially available SES (SES-anti-CD34, n = 7) and
      compared with GS (n = 8) and SES (n = 7) and examined at 3 and 14 days by
      scanning electron/confocal microscopy analysis. RESULTS: In phase 1, single stent
      implantation showed greatest endothelialization in GS (99%) and in bare-metal
      stent (99%) compared with SES (55%, p = 0.048). In overlapping stents,
      endothelialization at the overlapping zone was significantly greater in GS+GS (95
      +/- 6%) and GS+SES (79 +/- 5%) compared with the SES+SES (36 +/- 14%) group (p =
      0.007). In phase 2, SES-anti-CD34 resulted in increased endothelialization
      compared with SES alone at 3 days (SES-anti-CD34 36 +/- 26%; SES 7 +/- 3%; and GS
      76 +/- 8%; p = 0.01), and 14 days (SES-anti-CD34 82 +/- 8%; SES 53 +/- 20%; and
      GS 98 +/- 2%; p = 0.009). CONCLUSIONS: Immobilization of anti-CD34 antibody on
      SES enhances endothelialization and may potentially be an effective therapeutic
      alternative to improve currently available drug-eluting stents.

PMID- 20129573
TI  - Drug-eluting stent endothelium: presence or dysfunction.

PMID- 20129574
TI  - Role of endothelial progenitor cells in restenosis and progression of coronary
      atherosclerosis after percutaneous coronary intervention: a prospective study.
AB  - OBJECTIVES: We prospectively investigated the relationship of circulating
      endothelial progenitor cells at time of percutaneous coronary intervention to the
      subsequent development of in-stent restenosis or progression of coronary
      atherosclerosis. BACKGROUND: Endothelial progenitor cells provide an endogenous
      repair mechanism of the dysfunctional endothelium and therefore can play a
      pathogenic role in coronary atherosclerosis. METHODS: We studied 155 consecutive
      stable angina patients (92 men, age 60 +/- 11 years). All patients had flow
      cytometry the day before elective percutaneous coronary intervention in order to
      derive subpopulations of endothelial progenitor cells. A control group of 20
      normal subjects was considered for comparison. RESULTS: At 8-month control
      angiography, 30 patients showed in-stent restenosis (restenosis group), 22
      patients showed progression of coronary atherosclerosis (progression group),
      whereas the remaining 103 patients had neither in-stent restenosis nor
      progression of coronary atherosclerosis (stable group). Comparison of the 3
      groups did not show any difference in risk factors, cardiac morphology and
      function, extension of coronary artery disease, and treatment. Absolute numbers
      of CD34+/KDR+/CD45- cells (i.e., progenitors of endothelial lineage) measured in
      the restenosis group (1.41 +/- 0.64 cells/microl) were significantly higher than
      in the progression, stable, and control groups (1.03 +/- 0.53 cells/microl, 1.07
      +/- 0.46 cells/microl, and 0.95 +/- 0.44 cells/microl, respectively, p < 0.05).
      Similarly, CD133+/KDR+/CD45- cells (i.e., progenitors of endothelial cells at an
      earlier stage) were significantly higher in the restenosis (0.63 +/- 0.23
      cells/microl) compared with progression, stable, and control groups (0.33 +/-
      0.19 cells/microl, 0.41 +/- 0.32 cells/microl, and 0.36 +/- 0.15 cells/microl,
      respectively, p < 0.001). Also, numbers of CD14+/CD45+ cells (i.e., which have a
      role in angiogenesis via a paracrine effect) were significantly different among
      the restenosis, progression, stable, and control groups (0.72 +/- 0.56
      cells/microl vs. 0.51 +/- 0.52 cells/microl vs. 0.28 +/- 0.54 cells/microl vs.
      0.62 +/- 0.67 cells/microl, respectively, p < 0.05), whereas CD105+/CD45-/CD34-
      cells (i.e., which have a receptor for transforming growth factor-beta) were
      similar among groups. CONCLUSIONS: Patients with restenosis have higher numbers
      of subpopulations of endothelial progenitor cells that incorporate into
      endothelial cells or play a role in arteriogenesis compared with controls and
      patients with either progression of coronary atherosclerosis or stable disease.

PMID- 20129575
TI  - Understanding the role of endothelial progenitor cells in cardiovascular disease,
      coronary artery lesion progression, and in-stent restenosis.

PMID- 20129576
TI  - Increased restenosis rate after implantation of drug-eluting stents in patients
      with elevated serum activity of matrix metalloproteinase-2 and -9.
AB  - OBJECTIVES: Our aim was to test whether serum levels of matrix metalloproteinase
      (MMP)-2 and -9 are associated with the development of in-stent restenosis (ISR)
      after implantation of drug-eluting stents (DES). BACKGROUND: With the
      introduction of DES coronary ISR could be reduced dramatically. However, it still
      plays a significant role, particularly after treatment of multiple, complex
      lesions. METHODS: We studied 85 patients who were treated with 159 DES. Blood
      samples for measurement of MMP-2 and -9 antigen and activity were taken directly
      before and 24 h after percutaneous coronary intervention (PCI). Restenosis was
      evaluated at 6 to 8 months by coronary angiography. RESULTS: During the follow-up
      period, 2 patients (2.4%) died of cardiovascular causes, and 12 patients
      developed angiographic ISR. Patients with ISR showed significantly higher serum
      activity of MMP-9 at baseline (p = 0.017) and of MMP-2 (p < 0.0001) and MMP-9 (p
      < 0.0001) after the procedure. The PCI increased serum activity of MMP-2 (p =
      0.005) and MMP-9 (p = 0.008) only in patients with ISR. The restenosis rates of
      patients in the highest quartile of MMP-2 after and MMP-9 before and after PCI
      were 40.0%, 38.9%, and 42.9% compared with 6.3%, 7.7%, and 4.0% in the lower
      quartiles, respectively. This was independent of clinical and procedural
      characteristics. CONCLUSIONS: Elevated serum activities of MMP-2 and -9 are
      associated with dramatically increased restenosis rates after PCI with
      implantation of DES. Determination of MMP levels might be useful for
      identification of patients who are at high risk for ISR despite implantation of
      DES.

PMID- 20129577
TI  - Septal pouch in the left atrium: a new anatomical entity with potential for
      embolic complications.
AB  - OBJECTIVES: The purpose of this study was to develop a better understanding of
      the pathophysiology of the condition, we studied the patterns by which the septum
      primum (SP) and septum secundum (SS) fuse. BACKGROUND: A patent foramen ovale
      (PFO) is a communication across the interatrial septum between a nonadherent SP
      and SS and is considered to be a risk factor for serious clinical syndromes.
      METHODS: We examined the interatrial septum in 94 randomly selected autopsied
      hearts, with a focus on the SP and SS and the patterns by which the 2 structures
      fuse. RESULTS: Of the 94 specimens that were suitable for analysis, 26 (27.66%)
      had a PFO. Of the remaining 68 hearts, complete fusion of the SP and SS along the
      entire zone of overlap was seen in 27 (28.7%) hearts. In the remaining 41 hearts
      (60.29%), a PFO was absent, but incomplete fusion of the SP and SS was seen. Of
      41 hearts, 37 (90%) had a septal pouch that opened into the left atrial (LA)
      cavity. Four hearts (10%) had a pouch accessible from the right atrium. Hearts
      with left-sided pouches tended to be younger (50 +/- 18 years of age) than hearts
      where there was complete fusion (age 63 +/- 23 years) (p = 0.06). CONCLUSIONS:
      Our data suggest that when a foramen ovale closes spontaneously, the SP and SS
      fuse initially at the caudal limit of the zone of overlap of the 2 structures.
      This incomplete fusion results in a pouch that, in the majority of instances,
      communicates with the LA cavity.

PMID- 20129578
TI  - Pre-procedural imaging of aortic root orientation and dimensions: comparison
      between X-ray angiographic planar imaging and 3-dimensional multidetector row
      computed tomography.
AB  - OBJECTIVES: We sought to examine whether contrast-enhanced multidetector row
      computed tomography (MDCT) allows prediction of X-ray angiographic planes for the
      root angiogram in the context of transcatheter aortic valve implantation.
      BACKGROUND: Understanding of aortic root orientation relative to the body axis is
      critical for precise positioning of the stent/valve during transcatheter aortic
      valve implantation. METHODS: Forty patients with severe aortic stenosis underwent
      conventional X-ray angiography and contrast-enhanced MDCT of the aortic root.
      Oblique MDCT images of the aortic root, corresponding to X-ray angiographic left
      anterior oblique (LA)/right anterior oblique (RAO) projections, were created. The
      cranial/caudal angulation was compared between angiographic and reformatted MDCT
      images. In addition, root diameter measurements were compared. RESULTS: The
      cranial angulation in the LAO X-ray angiograms (mean LAO: 39+/- 8, n = 38) and
      matched MDCT images were not significantly different (cranial: 25 +/- 7 vs. 23 +/
      8; p = 0.214). There was a small but significant difference between the caudal
      angulation in the RAO angiogram (mean RAO: 25 +/- 5, n = 40) and matched CT
      images (caudal: 21 +/- 9 vs. 29 +/- 10; p = 0.002). The annulus diameter in the
      LAO projection was not significantly different between X-ray angiography and
      contrast-enhanced MDCT (2.3 +/- 0.3 vs. 2.4 +/- 0.3; p = 0.052), whereas there
      was a small but significant difference in the annulus diameter in RAO projections
      between angiography and MDCT (2.4 +/- 0.3 vs. 2.2 +/- 0.3; p = 0.029).
      CONCLUSIONS: Pre-procedural contrast-enhanced MDCT imaging of the aortic root
      allows prediction of X-ray angiographic planes and contributes to planning of the
      transcatheter aortic valve implantation.

PMID- 20129579
TI  - Use of balloon aortic valvuloplasty to size the aortic annulus before
      implantation of a balloon-expandable transcatheter heart valve.
AB  - OBJECTIVES: Our aim was to describe the use of balloon aortic valvuloplasty (BAV)
      to select proper transcatheter heart valve (THV) size. BACKGROUND:
      Transesophageal echocardiogram (TEE) measurement alone of the aortic annulus may
      not be adequate to select a THV size. BAV can more accurately size the aortic
      annulus. We report our experience using this strategy in patients undergoing THV
      implantation. METHODS: Twenty-seven patients underwent sizing of the aortic
      annulus by BAV and TEE. We implanted the minimal THV size that was greater than
      the annulus measured by BAV. RESULTS: The annulus measured by TEE was 21.3 +/-
      1.6 mm and by BAV was 22.6 +/- 1.8 mm (p < 0.001). The number of balloon
      inflations was 2.7 +/- 0.7 (range 2 to 4), and the balloon sizes used were 22.0
      +/- 1.8 mm (range 20 to 25 mm). Fourteen patients (52%) required upsizing of the
      initial balloon suggested by TEE; rapid pacing duration was 8 +/- 1.3 s (range 6
      to 11 s). No change in aortic insufficiency or hemodynamic instability occurred
      with BAV. Fifteen patients (56%) received a 23-mm THV; 12 patients a 26-mm THV.
      No coronary occlusion, annular damage, or THV embolization occurred. Paravalvular
      leak was grade <or=1 in all patients. In 7 patients (26%), balloon sizing
      resulted in selection of a specific THV size that could not be done by TEE alone.
      CONCLUSIONS: BAV sizing of the aortic annulus is safe and is an important adjunct
      to TEE when selecting THV size. Implanting the minimal THV greater than the BAV
      annulus size resulted in no adverse events. These data suggest that use of BAV
      for THV selection may improve the safety and efficacy of THV implantation.

PMID- 20129580
TI  - Post-implantation repositioning of the CoreValve percutaneous aortic valve.

PMID- 20129581
TI  - Bioprosthetic leaflet erosion after percutaneous mitral paravalvular leak
      closure.

PMID- 20129582
TI  - ASCERT: the American College of Cardiology Foundation--the Society of Thoracic
      Surgeons Collaboration on the comparative effectiveness of revascularization
      strategies.

PMID- 20129583
TI  - Early detection of iatrogenic pericardial effusion: importance of intracardiac
      echocardiography.

PMID- 20129585
TI  - A valuable public option.

PMID- 20129586
TI  - Welcoming a new decade and reflecting on the "2000s": considerations for the
      discipline of nursing.

PMID- 20129587
TI  - Part 1. Undergraduate nursing evidence-based practice education: envisioning the
      role of students.
AB  - Nursing educators have embraced the integration of evidence-based practice (EBP)
      into the nursing education curriculum in numerous ways. As this review of the
      nursing pedagogy literature demonstrates, most of these approaches built upon
      long-standing commitments to helping students understand the scientific research
      process, think critically, and develop the information literacy skills that will
      enable them to find the evidence that can inform their practice. Many reports in
      the nursing pedagogy literature recounted various strategies used to teach EBP to
      nursing students. Another category of nursing pedagogy articles discussed ways
      that EBP education can be suffused throughout the nursing school curriculum. Few
      educators, however, have envisioned students as having a role beyond that of the
      mere recipients of EBP education. Nonetheless, a small but growing number of
      nurse educators have begun to envision students as enablers of practice change in
      clinical settings. These innovators advocate a pedagogical paradigm that places
      students into socially meaningful partnerships with practicing nurses as a means
      to promote the uptake of EBP in clinical settings.

PMID- 20129588
TI  - Part II. Empowering grassroots evidence-based practice: a curricular model to
      foster undergraduate student-enabled practice change.
AB  - This article presents evidence collected over the past 15 years that attests to
      the success of curricular innovations conducted to foster socially meaningful
      contact between nursing students and practicing nurses as a means to promote
      evidence-based practice (EBP). Action research data collected as these
      pedagogical strategies have evolved suggest that such student-staff partnerships
      offer promise not only to encourage commitment to EBP among nursing students but
      also to surmount most of the barriers that prevent the widespread diffusion of
      EBP among practicing nurses in clinical settings. Based upon our successful
      experiences with student-staff interactions, we propose a curricular model-the
      Student-Enabled Practice Change model-that suffuses the undergraduate nursing
      school curriculum with opportunities for nursing students to form meaningful
      partnerships with practicing nurses. The Student-Enabled Practice Change
      Curricular Model relocates the power to drive practice change to the grassroots
      level of students and practicing nurses.

PMID- 20129589
TI  - Part III. Reenvisioning undergraduate nursing students as opinion leaders to
      diffuse evidence-based practice in clinical settings.
AB  - Rogers's claims about the importance of social networks to the diffusion of
      innovations are reviewed in light of efforts to promote evidence-based practice
      (EBP) among nursing students and practicing nurses. We argue that nursing
      educators can take more deliberate advantage of the essentially social nature of
      the diffusion process by devising opportunities for nursing students to form
      meaningful social interactions with practicing nurses. We recommend curricular
      reforms that reenvision undergraduate nursing students as opinion leaders
      throughout the curriculum. Rogers's theory predicts that such ongoing
      interactions between nursing students and practicing nurses will better integrate
      EBP among both populations.

PMID- 20129590
TI  - Are regulations more consumer-friendly when boards of nursing are the sole
      regulators of nurse practitioners?
AB  - The widely varied regulations in the 50 states often limit consumer access to
      nurse practitioners (NPs). In 22 states, the Board of Nursing (BON) must share NP
      regulatory authority with another profession, usually physicians. This study
      examines the relationship between the BON as the sole authority regulating NPs or
      sharing that authority with another profession and the NP regulatory environment.
      Independent t tests compared the NP regulatory environments for consumer access
      and choice in states with sole BON regulation with those in states with
      involvement of another profession. The states' NP regulatory environments were
      quantified with an 11-measure tool assessing domains of consumer access to NPs,
      NP patients' access to service, and NP patients' access to prescription
      medications. BON-regulated states were less restrictive (P < .01, effect size
      1.02) and supported NP professional autonomy. Entry into practice regulations did
      not differ in the two groups of states. Having another profession involved in
      regulation correlates with more restrictions on consumer access to NPs and more
      restrictions to the full deployment of NPs.

PMID- 20129591
TI  - Baccalaureate nursing graduates' perceptions of their clinical instructional
      experiences and preparation for practice.
AB  - Clinical competence is essential to fulfill the role of a registered professional
      nurse. In light of the changing health care environment, the American Association
      of Colleges of Nursing and the Institute of Medicine have recommended that health
      care professionals be proficient in specific areas. To meet the needs of today's
      graduates, nursing education must reexamine the academic and clinical preparation
      of nurses. This case study sought to identify the perceptions of recent
      baccalaureate nursing graduates regarding their academic clinical experiences and
      if they felt prepared to enter the practice arena. Quantitative and qualitative
      methods were used to obtain data in the form of a mailed self-administered
      questionnaire developed by the researcher. Statistical analysis indicated that,
      although the academic clinical experiences were generally positive, there were
      significant differences in what actually occurred and what graduates deemed
      important for their preparation for practice. Effective clinical teaching
      practices were identified in the findings as well. Clinical instructional
      experiences are viewed as an important opportunity for students to become
      prepared for entry into practice. Faculty must be aware of effective teaching
      practices and be supported in that role. A preceptor type of experience was noted
      to be the most effective clinical experience in preparing students for the
      reality of independent practice. Nursing education must reexamine current
      approaches to clinical teaching and seek methods to better prepare future nurses.

PMID- 20129592
TI  - The impact of clinical nurse specialists on clinical pathways in the application
      of evidence-based practice.
AB  - The purpose of this article was to address the call for evidence-based practice
      through the development of clinical pathways and to assert the role of the
      clinical nurse specialist (CNS) as a champion in clinical pathway implementation.
      In the current health care system, providing quality of care while maintaining
      cost-effectiveness is an ever-growing battle that institutions face. The CNS's
      role is central to meeting these demands. An extensive literature review has been
      conducted to validate the use of clinical pathways as a means of improving
      patient outcomes. This literature also suggests that clinical pathways must be
      developed, implemented, and evaluated utilizing validated methods including the
      use of best practice standards. Execution of clinical pathways should include a
      clinical expert, who has the ability to look at the system as a whole and can
      facilitate learning and change by employing a multitude of competencies while
      maintaining a sphere of influence over patient and families, nurses, and the
      system. The CNS plays a pivotal role in influencing effective clinical pathway
      development, implementation, utilization, and ongoing evaluation to ensure
      improved patient outcomes and reduced costs. This article expands upon the call
      for evidence-based practice through the utilization of clinical pathways to
      improve patient outcomes and reduce costs and stresses the importance of the CNS
      as a primary figure for ensuring proper pathway development, implementation, and
      ongoing evaluation.

PMID- 20129593
TI  - Learning styles of registered nurses enrolled in an online nursing program.
AB  - BACKGROUND: Technological advances assist in the proliferation of online nursing
      programs which meet the needs of the working nurse. Understanding online learning
      styles permits universities to adequately address the educational needs of the
      professional nurse returning for an advanced degree. PURPOSE: The purpose of this
      study was to describe the learning styles of registered nurses (RNs) enrolled in
      an online master's nursing program or RN-bachelor of science in nursing (BSN)
      program. METHOD: A descriptive, cross-sectional design was used. Kolb's learning
      style inventory (Version 3.1) was completed by 217 RNs enrolled in online courses
      at a Southeastern university. Descriptive statistical procedures were used for
      analysis. DISCUSSION: Thirty-one percent of the nurses were accommodators, 20%
      were assimilators, 19% were convergers, and 20% were divergers. Accommodators
      desire hand-on experiences, carrying out plans and tasks and using an intuitive
      trial-and-error approach to problem solving. CONCLUSIONS: The learning styles of
      the RNs were similar to the BSN students in traditional classroom settings.
      Despite their learning style, nurses felt that the online program met their
      needs. Implementing the technological innovations in nursing education requires
      the understanding of the hands-on learning of the RN so that the development of
      the online courses will satisfactorily meet the needs of the nurses who have
      chosen an online program.

PMID- 20129594
TI  - Trends in self-rated health among nurses: a 4-year longitudinal study on the
      transition from nursing education to working life.
AB  - For nurses, the transition from higher education to working life involves several
      types of changes and seems to be a major contributing cause of distress and,
      consequently, ill health on a longer term basis. The aim of this study was to
      longitudinally monitor the development of self-rated health (SRH) in nurses,
      starting from the last semester at the university with subsequent follow-ups when
      the nurses had entered working life. The Longitudinal Analyses of Nurses'
      Education and working life is an ongoing nationwide longitudinal project focusing
      on mapping health and career development in nurses in Sweden. SRH is one of the
      most widely used single-item measures of perceived health status with a well
      established predictive ability on future health outcomes, including morbidity and
      mortality. This study found a small but significant and continuous decline in SRH
      among nurses during 3 years of follow-ups, starting from their last semester of
      nursing education and continuing 3 years into their working life. The most
      pronounced decline in SRH seems to occur in the transition between student life
      and working life and is most explicit among the youngest nurses. However, the
      long-term effect on SRH when entering into working life seems to be more
      pronounced among the older nurses.

PMID- 20129595
TI  - Scholar in Residence: an innovative application of the scholarship of engagement.
AB  - Universities are expected to engage with communities for the benefit of both.
      Based on the definition of scholarship advanced by Boyer in the 1990s, inclusive
      of the scholarship of discovery, integration, teaching, and application, the
      School of Nursing and Jewish Geriatric Services, Inc., have instituted a unique
      collaboration entitled the Scholar in Residence. Unlike traditional agreements
      between schools of nursing and agencies to provide clinical experience and
      educate students, this agreement is designed to build scholarship for both
      university and agency. Outcomes include building opportunities for faculty and
      staff scholarship at the agency, enhancing the integration of knowledge into
      practice, intensifying opportunities for the sharing of knowledge by providing
      opportunities for students to work with faculty and staff on individual projects,
      and enriching the application of knowledge by providing opportunities for faculty
      clinical practice and consultation. The Scholar in Residence is a model of
      collaboration between the university and the community that reflects the mission
      of the university and provides value to the community agency through strategic
      engagement of both entities.

PMID- 20129596
TI  - [The singing voice].
AB  - Singing voice is a special subgroup within the field of voice. In addition to the
      differences in physiology between singing and speaking voice, singer patients are
      often regarded as a challenge for the otolaryngologist. The reason for this is
      probably that the field of voice has not received as much attention as others in
      our speciality. Moreover, in the case of singers, empathy is vital in the doctor
      patient relationship, and, as in many other cases, it forms part of the
      therapeutic effect. In order to achieve this, the physician has to know what
      singers are and which are the main pathologies they suffer, how they are formed
      and how they are expressed. This review offers an overlook of the pathological
      physiology of singing voice from a double point of view, scientific and artistic,
      which in the case of singing are inevitably linked.

PMID- 20129597
TI  - The impact of Relative Prevalence on dual-target search for threat items from
      airport X-ray screening.
AB  - The probability of target presentation in visual search tasks influences target
      detection performance: this is known as the prevalence effect (Wolfe et al.,
      2005). Additionally, searching for several targets simultaneously reduces search
      performance: this is known as the dual-target cost (DTC: Menneer et al., 2007).
      The interaction between the DTC and prevalence effect was investigated in a
      single study by presenting one target in dual-target search at a higher level of
      prevalence than the other target (Target A: 45% Prevalence; Target B: 5%
      Prevalence). An overall DTC was found for both RTs and response accuracy.
      Furthermore, there was an effect of target prevalence in dual-target search,
      suggesting that, when one target is presented at a higher level of prevalence
      than the other, both the dual-target cost and the prevalence effect contribute to
      decrements in performance. The implications for airport X-ray screening are
      discussed.

PMID- 20129598
TI  - Defining criteria for the functional assessment of driving.
AB  - Given the growing number of older drivers, accurate functional assessment of
      fitness to drive is becoming increasingly important. This paper describes work to
      define appropriate thresholds for cognitive, perceptual and physical tests on a
      static assessment rig (SAR). These rigs are used at Mobility Centres across the
      UK to provide measurements of driving characteristics as part of an assessment.
      However, criteria for decisions on functional fitness to drive have not been
      clearly defined or validated for SARs. A first study obtained normative data from
      the non-disabled driving population for each of the SAR tests. In the second
      study, disabled drivers were tested on the SAR; approximately half of these
      drivers used some type of steering, braking or accelerator adaptation. Following
      these two studies, criteria for the SAR tests were formalised and then validated
      by means of an experimental trial. Recommendations are made regarding the use of
      the SAR as part of the overall assessment process and for future research.

PMID- 20129599
TI  - Systems mapping workshops and their role in understanding medication errors in
      healthcare.
AB  - Systems mapping workshops have been applied to the problem of medication errors
      in healthcare. The workshops were designed using experiential group work
      principles. They involved a range of stakeholders from within the health service
      as well as those who supply the health sector, including designers who may be
      able to enhance the safety of products and systems used in healthcare. Research
      has shown that the method encourages stakeholder participation, provides robust
      results within a limited time and enhances understanding across specialist
      interest groups. Additional, creative design workshops that considered the same
      topic showed significant promise in developing concepts from which potential
      solutions could be developed further.

PMID- 20129600
TI  - Visually induced motion sickness, visual stress and photosensitive epileptic
      seizures: what do they have in common? - preface to the special issue.

PMID- 20129601
TI  - Eye movements reduce vividness and emotionality of "flashforwards".
AB  - Earlier studies have shown that eye movements during retrieval of disturbing
      images about past events reduce their vividness and emotionality, which may be
      due to both tasks competing for working memory resources. This study examined
      whether eye movements reduce vividness and emotionality of visual distressing
      images about feared future events: "flashforwards". A non-clinical sample was
      asked to select two images of feared future events, which were self-rated for
      vividness and emotionality. These images were retrieved while making eye
      movements or without a concurrent secondary task, and then vividness and
      emotionality were rated again. Relative to the no-dual task condition, eye
      movements while thinking of future-oriented images resulted in decreased ratings
      of image vividness and emotional intensity. Apparently, eye movements reduce
      vividness and emotionality of visual images about past and future feared events.
      This is in line with a working memory account of the beneficial effects of eye
      movements, which predicts that any task that taxes working memory during
      retrieval of disturbing mental images will be beneficial.

PMID- 20129602
TI  - A simple, mild, and regioselective method for the benzylation of carbohydrate
      derivatives promoted by silver carbonate.
AB  - A simple, mild, and regioselective method has been developed for the selective
      benzylation and p-methoxybenzylation of carbohydrate derivatives in high yields
      using Ag(2)CO(3) as the promoter. Benzylation of base-labile substrates, for
      which other reported methods are of little use, has been performed in high
      yields.

PMID- 20129603
TI  - Mapping introspection's blind spot: reconstruction of dual-task phenomenology
      using quantified introspection.
AB  - Psychologists often dismiss introspection as an inappropriate measure, yet
      subjects readily volunteer detailed descriptions of the time and effort that they
      spent on a task. Are such reports really so inaccurate? We asked subjects to
      perform a psychological refractory period experiment followed by extensive
      quantified introspection. On each trial, just after their objective responses,
      subjects provided no less than four subjective estimates of the timing of
      sensory, decision and response events. Based on these subjective variables, we
      reconstructed the phenomenology of an average trial and compared it to objective
      times and to predictions derived from the central interference model.
      Introspections of decision time were highly correlated with objective measures,
      but there was one point of drastic distortion: subjects were largely unaware that
      the second target was waiting while the first task was being completed, the
      psychological refractory period effect. Thus, conscious perception is
      systematically delayed and distorted while central processing resources are
      monopolized by another task.

PMID- 20129604
TI  - Body burdens of brominated flame retardants and other persistent organo
      halogenated compounds and their descriptors in US girls.
AB  - BACKGROUND: Levels of brominated flame retardants are increasing in US
      populations, yet little data are available on body burdens of these and other
      persistent hormonally active agents (HAAs) in school-aged children. Exposures to
      such chemicals may affect a number of health outcomes related to development and
      reproductive function. OBJECTIVE: Determine the distribution of biomarkers of
      polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and
      organo-chlorinated pesticides (OCPs), such as DDT/DDE, in children, and their
      variation by key descriptor variables. METHODS: Ethnically diverse cohorts of
      girls 6-8 y old at baseline are being followed for growth and pubertal
      development in a multi-site, longitudinal study. Nearly 600 serum samples from
      the California and Ohio sites were analyzed for lipids, 35 PCB congeners, 11 PBDE
      congeners, and 9 OCPs. The biomarker distributions were examined and geometric
      means compared for selected analytes across categories of age, race, site, body
      mass index (BMI), parental education, maternal age at delivery, and breast
      feeding in adjusted models. RESULTS: Six PBDE congeners were detected among
      greater than 70% of samples, with BDE-47 having the highest concentration (median
      42.2, range 4.9-855 ng/g lipid). Girls in California had adjusted geometric mean
      (GM) PBDE levels significantly higher than girls in Ohio. Furthermore, Blacks had
      significantly higher adjusted GMs of all six PBDE congeners than Whites, and
      Hispanics had intermediate values. GMs tended to be lower among more obese girls,
      while other variables were not strongly associated. In contrast, GMs of the six
      PCB congeners most frequently detected were significantly lower among Blacks and
      Hispanics than Whites. PCBs and the three pesticides most frequently detected
      were also consistently lower among girls with high BMI, who were not breast-fed,
      whose mothers were younger, or whose care-givers (usually parents) were less
      educated. Girls in California had higher GMs than in Ohio for the pesticides and
      most PCB congeners, but the opposite for CB-99 and -118. CONCLUSIONS: Several of
      these potential HAAs were detected in nearly all of these young girls, some at
      relatively high levels, with variation by geographic location and other
      demographic factors that may reflect exposure pathways. The higher PBDE levels in
      California likely reflect differences in fire regulation and safety codes, with
      potential policy implications.

PMID- 20129605
TI  - A community-based assessment of seafood consumption along the lower James River,
      Virginia, USA: potential sources of dietary mercury exposure.
AB  - The use of community-based participatory research (CBPR) methods to conduct
      environmental exposure assessments provides valuable insight about disparities in
      seafood consumption and contaminant exposure. Ninety-five community-specific
      seafood consumption surveys were administered to low-income African-American
      women (ages 16-49) residing in the Southeast community of Newport News, VA, USA,
      for the purpose of assessing potential dietary mercury exposure. Only the results
      of the seafood consumption surveys are presented in this manuscript.
      Approximately 65% of the women surveyed do not fish; however, 83% had consumed
      seafood within the last 7 days. Whiting, shrimp, and canned tuna were the three
      items most frequently consumed. Ninety-three percent of the women surveyed stated
      that grocery/seafood markets were the main sources of the seafood items generally
      consumed. The mean seafood consumption rate for the women surveyed was 147.8
      g/day (95% CI: 117.6-185.8), a rate substantially higher than the mean seafood
      consumption rate reported for US women (1.8 g/day 95% CI: 1.51-2.04). Shrimp,
      croaker, and blue crab were the top three seafood items with the highest summed
      amount (g/day) consumed. There was no significant association between demographic
      variables (age, income, education, and weight) and total number of seafood items
      listed, ingestion rate (g/meal), exposure frequency (meals/year), and seafood
      consumption rate (g/day). By using CBPR to assess seafood consumption in this
      community, we learned that even though women in Southeast Newport News, Virginia
      are not subsistence fishers, they consume seafood at a subsistence fisher rate.
      Of the three seafood items most frequently consumed, canned tuna potentially
      plays a significant role in dietary mercury exposure for women in this community.
      Future work includes determining mercury concentrations in seafood items consumed
      and generating community-specific statements of dietary mercury risks.

PMID- 20129606
TI  - Orthopaedic trauma in the obese patient.

PMID- 20129607
TI  - A reliable method of maintaining constant arthroscopy irrigation pressure.

PMID- 20129608
TI  - Inadequate identification of small-for-gestational-age fetuses at an urban
      teaching hospital.
AB  - OBJECTIVE: To ascertain the likelihood of identifying small for gestational age
      (SGA) neonates prenatally (below the 10th percentile for gestational age).
      METHODS: On admission for delivery, the charts of singletons with reliable
      gestational age (GA) were reviewed to determine whether intrauterine growth
      restriction (IUGR) was suspected, clinically or sonographically. Multiple
      logistic regression analysis was used with the accurate identification of SGA as
      the dependent variable and 13 independent variables. RESULTS: Over 10 months,
      1502 pregnant women met the inclusion criteria and 16% of neonates were born SGA.
      Before delivery, only 10% (95% confidence interval 6%-14%) of newborns identified
      as SGA were detected, and 7% weighed below the 5th percentile. Multiple logistic
      regression analysis identified 4 factors that made a significant independent
      contribution to the detection of SGA: younger maternal age, size less than date,
      sonographic examination within 4 weeks of delivery, and a history of substance
      abuse. CONCLUSIONS: Because we failed to identify 90% of SGA with fundal height
      measurements, the likelihood of detecting most growth-restricted fetuses
      clinically is low. If other investigators confirm these findings, a paradigm
      shift is warranted to improve the detection of IUGR.

PMID- 20129609
TI  - Magnet Hospital attributes in European hospitals: a multilevel model of job
      satisfaction.
AB  - BACKGROUND: The Magnet Recognition Program in the USA has been based on 14
      hospital characteristics that were common in hospitals that were "magnets" for
      professional nurses. While the program has expanded to other countries, no
      research has explored how the concept translates to other cultures and healthcare
      systems, nor have multilevel approaches been used. OBJECTIVE: The primary aim of
      this study was to explore the presence of Magnet Hospital attributes in hospitals
      in two European countries. In addition, the relationship between Magnet Hospital
      attributes and nurses' job satisfaction was examined at both the nurse and the
      hospital level. DESIGN: A secondary data analysis with cross-sectional design was
      conducted. A multilevel approach was taken to account for the hospital effect due
      to the nested nature of the data. SETTINGS: Nurses practicing in acute care
      hospitals in Germany (16) and Belgium (15) were examined. Hospitals that had less
      than five respondents were excluded. PARTICIPANTS: Survey responses from 2303
      registered nurses (RNs) from Belgium and 2646 RNs from Germany were included. Non
      RN providers, RNs with administrative positions, and those working in non
      inpatient areas were excluded. The final sample was 3182 staff nurses working in
      acute care hospitals. METHODS: Magnet Hospital attributes that might be
      represented in NEXT survey items were reviewed by an expert panel before
      psychometric testing. Only six Magnet Forces could be measured. Latent constructs
      of these forces and job satisfaction were established. The measurement models and
      structural regression models were estimated using multilevel modeling in Mplus
      4.21. RESULTS: Six Magnet Forces were validated by two-level confirmatory factor
      analyses, with good fit to the data as demonstrated by the fit indices. All six
      Magnet Forces significantly predicted job satisfaction at the nurse level, with
      personnel policies having the strongest effect (b=0.96). At the hospital level,
      management style had the strongest effect (b=0.84) in predicting job
      satisfaction, followed by professional development, interdisciplinary
      relationship, and autonomy. CONCLUSIONS: Magnet Hospital attributes are evident
      in hospitals in two European countries and were found to be associated with job
      satisfaction. Further multilevel research should explore these attributes
      particularly at the nursing unit-level where work environment is experienced.

PMID- 20129610
TI  - Accuracy of body mass index to determine obesity in women with breast cancer: an
      observational study of Taiwanese sample.
AB  - BACKGROUND: Obesity is common in women with breast cancer. The risk of obesity
      induced metabolic syndrome is higher in Asians than in Caucasians. Excessive body
      fat accumulation has been associated with a worse prognosis. However, the most
      popular clinical indicator of obesity is not fat itself, but body mass index
      (BMI). OBJECTIVES: The purposes of this study were to determine the consistency
      of BMI and body fat percentage (BF%) in determining obesity and to identify the
      best BMI cutoffs for identifying obesity in Taiwanese women with breast cancer.
      METHODS: Body fat and fat-free mass were measured by bioelectrical impedance 1
      day before breast surgery for 200 women with breast cancer. BMI was calculated as
      weight (in kilograms) divided by height (in meters) squared. RESULTS: BMI and BF%
      were highly correlated (r=0.91; p<0.001). However, BMI exhibited poor sensitivity
      for identifying obesity (47%). The sensitivity of BMI to detect obesity was
      better in women over age 60. The best BMI cutoff for obesity was 22.3 kg/m2 with
      a sensitivity and specificity of 89% (95% CI=83-94%) and 87% (95% CI=77-93%)
      respectively, and the total accuracy rate improved from 65% to 89%. CONCLUSIONS:
      Using BMI to identify obesity in Taiwanese women with breast cancer requires
      careful attention to the diagnostic criterion chosen. The World Health
      Organization criterion tends to underestimate the prevalence of obesity,
      especially for younger women with breast cancer (under age 40).

PMID- 20129611
TI  - Plasma bilirubin and gamma-glutamyltransferase activity are inversely related in
      dyslipidemic patients with metabolic syndrome: relevance to oxidative stress.
AB  - BACKGROUND: Subnormal levels of plasma bilirubin levels are associated with
      premature coronary artery disease and cardiovascular morbidity. Plasma gamma
      glutamyltransferase (GGT) activity is linked to bilirubin level in hepatic
      disease and elevated GGT is equally associated with hepatic steatosis, a frequent
      feature of metabolic syndrome (MS). In order to assess the potential relationship
      between GGT activity and bilirubin levels in subjects exhibiting features of the
      metabolic syndrome, we determined circulating bilirubin levels and GGT activity
      in a cohort of dyslipidemic patients. METHODS AND RESULTS: This cross-sectional
      study involved patients (n=1433) displaying atherogenic dyslipidemia in primary
      prevention referred to our Prevention Center. Among these patients, 25% presented
      with MS as defined by recent NCEP ATP III criteria. Circulating levels of
      transaminases, as well as GGT activity, were elevated in MS patients; by
      contrast, bilirubin concentrations were significantly lower in such patients as
      compared to those lacking this syndrome (p<10-4 for all comparisons). Comparisons
      of patient groups on the basis of the number of MS criteria which were
      concomitantly present revealed a progressive decrease in mean bilirubin levels;
      this reduction paralleled a progressive increase in mean GGT activity as a
      function of the number of MS components in the overall population (p value for
      trend<10-4). CONCLUSION: Elevation in systemic GGT activity, which is
      characterized by extended generation of ROS, together with potentially deficient
      bilirubin-mediated antioxidative capacity of plasma, may therefore constitute key
      components of the systemic oxidative stress typical of metabolic syndrome.

PMID- 20129612
TI  - Nano-emulsions prepared by the phase inversion composition method: preparation
      variables and scale up.
AB  - The aim of this work is to study, through experimental design, the effect of
      vessel geometry and scale-up in the properties of nano-emulsions prepared through
      the phase inversion composition method (PIC). Results show that a proper mixing
      is crucial for small droplet-sized nano-emulsions, especially when remaining free
      oil is found together with the key liquid crystal phase formed during the
      emulsification process. In these cases, mixing must be near the perfect mixed
      model. Proper geometries must be selected to promote a good mixture. Small
      addition rates V(ad) and high mixing rates omega promote the necessary mixing
      level. However, results indicate that, if free oil remains together with liquid
      crystal formed during emulsification, a too high omega could promote coalescence
      of oil droplets. When a cubic liquid crystal phase Pm3n is formed instead during
      emulsification, without free oil, coalescence is not promoted, probably due to
      the extremely high viscosity. For the system where Pm3n is formed during
      emulsification, scale-up cannot be done, as it would be expected, maintaining
      adimensional variables--Reynolds, Re, and adimensional time. A perfect
      correspondence between scales is observed when the total addition time and the
      lineal mixing rate are maintained between scales instead. Re, i.e. the ratio
      between inertial and viscous forces, does not seem adequate to describe the
      system, as inertial forces are worthless due to the extremely high viscosity.

PMID- 20129613
TI  - A modified microbial adhesion to hydrocarbons assay to account for the presence
      of hydrocarbon droplets.
AB  - The microbial adhesion to hydrocarbons (MATH) assay has been used widely to
      characterize microbial cell hydrophobicity and/or the extent of cell adhesion to
      hydrophobic liquids. The classical MATH assay involves spectrophotometric
      absorbance measurements of the initial and final cell concentrations in an
      aqueous cell suspension that has been contacted with a hydrocarbon liquid. In
      this study, microscopic examination of the aqueous cell suspension after contact
      with hexadecane or a hexadecane/toluene mixture revealed the presence of
      hydrocarbon droplets. The hydrocarbon droplets contributed to the absorbance
      values during spectrophotometric measurements and caused erroneous estimates of
      cell concentrations and extents of microbial adhesion. A modified MATH assay that
      avoids such artefacts is proposed here. In this modified assay, microscopic
      examination of the aqueous suspension and direct cell counts provides cell
      concentrations that are free of interference from hydrocarbon droplets. The
      presence of hydrocarbon droplets was noted in MATH assays performed with three
      bacterial strains, and two different hydrocarbons, at ionic strengths of 0.2 mM
      and 20 mM and pH 6. In these experiments, the formation of quasi-stable
      hydrocarbon droplets cannot be attributed to the presence of biosurfactants, or
      stabilization by biocolloids. The presence of surface potential at the
      hydrocarbon-water interface that was characterized by electrophoretic mobility of
      up to -1 and -2 microm cm/Vs, likely caused the formation of the quasi-stable
      hydrocarbon droplets that provided erroneous results using the classical MATH
      assay.

PMID- 20129614
TI  - Physicochemical characterization of silylated functionalized materials.
AB  - Silylation of several materials where the surface area arises from the internal
      pores (MCM-41 and FSM-16) or is essentially external (silica gel, and clays) was
      performed using three organosilanes: (3-aminopropyl)triethoxysilane (APTES), 4
      (triethoxysilyl)aniline (TESA) and (3-mercaptopropyl)trimethoxysilane (MPTS). The
      materials were characterized by nitrogen adsorption-desorption at -196 degrees C,
      powder XRD, XPS, bulk chemical analysis, FTIR and (29)Si and (13)C MAS NMR. For
      MCM-41 and FSM-16 the highest amounts of organosilane are obtained for APTES,
      while for the remaining materials the highest amounts are for MPTS; TESA always
      anchored with the lowest percentage. In terms of surface chemical analysis, TESA
      anchored with the highest contents irrespectively of the material, and the
      opposite is registered for MPTS. Comparison of bulk vs surface contents indicate
      that TESA is mainly anchored at the material external surface. Moreover, with N
      or S (surface and bulk) contents expressed per unit of surface area, MCM-41 and
      FSM-16 (internal porosity) show the lowest amounts of silane; the highest amounts
      of silane per unit of surface area are obtained for the clays. Grafting of the
      organosilanes to the surface hydroxyl groups was corroborated by FTIR and (29)Si
      and (13)C MAS NMR. Furthermore, NMR data suggested that TESA and APTES grafted
      mostly through a bidentate approach, whereas MPTS grafted by a monodentate
      mechanism.

PMID- 20129615
TI  - Aqueous coating dispersion (pseudolatex) of zein improves formulation of
      sustained-release tablets containing very water-soluble drug.
AB  - Zein is an alcohol soluble protein of corn origin that exhibits hydrophobic
      properties. Pseudolatexes are colloidal dispersions containing spherical solid or
      semisolid particles less than 1 microm in diameter and can be prepared from any
      existing thermoplastic water-insoluble polymer. The novel plasticized film
      coating pseudolatex of zein was studied in formulation of sustained-release
      tablets containing very water-soluble drug. Film formation of plasticized aqueous
      dispersion was compared with film forming properties of plasticized organic
      solvent system (ethanol) of zein. The water vapor permeability (WVP), water
      uptake and erosion, and moisture sorption were evaluated with free films. The
      tablets containing metoprolol tartrate as a model drug were used in pan-coating
      experiments. Aqueous film coatings plasticized with PEG 400 exhibited very low
      water uptake. No significant difference in WVP, moisture sorption and erosion
      were found between aqueous films and organic solvent-based films of zein
      plasticized with PEG 400. The atomic force microscopy (AFM) images on
      microstructure of films showed that colloidal particle size of zein in the
      aqueous films was smaller than that observed in the solvent-based films. In
      addition, the aqueous-based films were more compact and smoother than the
      respective solvent-based films. The aqueous zein-coated tablets containing very
      water-soluble drug (metoprolol tartrate) exhibited clear sustained-release
      dissolution profiles in vitro, while the respective solvent-based film-coated
      tablets showed much faster drug release. Furthermore, aqueous zein-coated tablets
      had lower water absorption at high humidity conditions. In conclusion, the
      plasticized aqueous dispersion (pseudolatex) of zein can be used for moisture
      resistant film coating of sustained-release tablets containing very water-soluble
      drug.

PMID- 20129616
TI  - A study on the potential application of natural phosphate in photocatalytic
      processes.
AB  - In an attempt at increasing surface area of the resulting solids, different
      titanium-based systems were synthesized on natural phosphate through the sol-gel
      process using diverse ageing conditions (reflux, magnetic stirring, sonication or
      microwaves) and tested for gas-phase selective photooxidation of propan-2-ol. The
      best results were obtained for the system aged under ultrasounds which was
      ascribed to its lower band-gap energy. Moreover, the synthesis of TiO(2) on
      natural phosphate seemed to produce retardation in crystallization as well as a
      change in titanium and phosphorus electronic environments (as determined by XPS)
      which in the case of the sonicated system resulted in an improved catalytic
      behavior as compared to pure titania. All in all, the present piece of research
      shows that provided that its surface area can be increased natural phosphate can
      be used as support for a photocatalytic active phase thus widening the scope of
      its application.

PMID- 20129617
TI  - A versatile method for the preparation of water-soluble amphiphilic oligomer
      coated semiconductor quantum dots with high fluorescence and stability.
AB  - High quality water-soluble semiconductor CdSe quantum dots (QDs) were prepared by
      a phase transfer method, in which amphiphilic oligomers (polymaleic acid
      aliphatic alcohol ester) was used as surface coating agents. The as-prepared
      aqueous QDs were high fluorescent and extremely stable. Fourier transform
      infrared spectroscopy, thermogravimetric analysis, and transmission electron
      microscopy all indicated that the surfaces of the QDs were coated with
      amphiphilic oligomers. Alkyl chain length of the amphiphilic oligomers could
      dramatically affect the phase transfer efficiency. It was found that the use of
      polymaleic acid n-hexadecanol ester had the best result. A biocompatible test has
      been carried out and such prepared water-soluble QDs were used to target tumor
      cells and found that the oligomer-functionalized QDs were excellent fluorescence
      labels for detecting the human hepatoma cells.

PMID- 20129618
TI  - Simulations of color development in tinted paints.
AB  - Monte Carlo simulations have been used to investigate how several thermodynamic
      and kinetic factors affect the distribution of pigments, when a water-based
      pigment dispersion is added to a solvent-borne paint. Our model contains three
      types of lattice particles: water, pigment and organic solvent, with short-ranged
      interactions. These particles move through biased diffusion, with a species
      dependent mobility. Moreover, to mimic the crosslinking of the resin, the
      mobility of the solvent particles decreases in time. Also, the water of the
      pigment dispersion evaporates slowly. First, we study which conditions yield the
      desired equilibrium phase behavior, with homogeneously distributed pigment. Next,
      we study how kinetics can prevent the system to reach equilibrium. We present
      examples in which these kinetic processes prevent dispersion in spite of
      favorable equilibrium conditions, as well as examples in which a homogeneous
      distribution is reached against unfavorable equilibrium conditions.

PMID- 20129619
TI  - Low temperature synthesis of visible light-driven vanadium doped titania
      photocatalyst.
AB  - A simple method based on sol-gel method was developed to prepare vanadium ions
      doped TiO(2) nanocrystalline at low temperature. Thus-obtained vanadium doped
      TiO(2) was proved to be V(x)Ti(1-x)O(2) solid solution. Doping vanadium could
      enhance the formation of stable phase. Its optical absorption spectrum shows a
      red shift to 445 nm. Photodegradation experiments suggest that thus-prepared
      vanadium doped TiO(2) nanocrystalline can be excited by visible light and is a
      good photocatalyst under daylight. These properties are the same as the vanadium
      doped TiO(2) prepared under high temperature conditions (> or = 350 degrees C).
      However, in the present work, the vanadium doped TiO(2) crystal particle is very
      uniform and fine, about 5 nm. It is much smaller than the production prepared
      under high temperature.

PMID- 20129620
TI  - Synthesis and photocatalytic properties of hierarchical metal nanoparticles/ZnO
      thin films hetero nanostructures assisted by diblock copolymer inverse micellar
      nanotemplates.
AB  - Metal dot-on-ZnO type hierarchical nanostructures composed of ordered arrays of
      noble metal nanoparticles with controlled areal density, prepared from
      poly(styrene-block-vinyl pyridine) diblock copolymer inverse micelles loaded with
      metal precursors, on sol-gel process based approximately 48 nm thick ZnO thin
      films exhibit enhanced photocatalytic activities compared with pure ZnO thin
      films in terms of photodegradation of methylene blue.

PMID- 20129621
TI  - Calcium carbonate-hydrolyzed soy protein complexation in the presence of citric
      acid.
AB  - The influence of hydrolyzed soy proteins on calcium carbonate stabilization was
      studied in citric acid solution. Calcium-soy proteins interactions were
      characterized using a calcium ion selective electrode, turbidity, and Isothermal
      Titration Calorimetry. Once the meta-stable phase was reached or just after soy
      protein addition, spray-drying was performed and SEM, XRD, and XPS analysis were
      carried out on spray-dried powders. In citric acid solution calcite crystals were
      eroded giving rise to smaller amorphous particles. In the presence of soy
      proteins, complexation exothermic in nature occurred with the mineral phase,
      which prevented CaCO(3) from recrystallisation and kept the system in an
      amorphous state. SEM performed on spray-dried powder showed that soy proteins
      were swollen in presence of mineral phase and resulted in a decrease of calcium
      concentration at the extreme surface of the studied powders as demonstrated by
      XPS.

PMID- 20129622
TI  - Preparation of highly hydrophobic and lipophobic cellulose fibers by a
      straightforward gas-solid reaction.
AB  - This work describes a very simple, rapid, and efficient approach to the
      hydrophobization and lipophobization of cellulose fibers through their reaction
      with gaseous trichloromethylsilane (TCMS). The characterization of the modified
      surface involved FTIR-ATR and solid-state (29)Si NMR spectroscopy, scanning
      electron microscopy (SEM), and contact angle measurements with different liquids.
      The modification generated an inorganic coating around the fibers, associated
      with the construction of a three-dimensional network of Si-O-Si bridges partly
      bound to the polysaccharide macromolecules. This coating conferred both a high
      hydrophobicity and a lipophobicity to the samples even when the treatments
      applied modest TCMS quantities and reaction times as short as 30 s. The green
      connotation of this novel process constitutes an additional positive feature.

PMID- 20129623
TI  - Solubilisation of model adjuvants by Pluronic block copolymers.
AB  - The effect of two model adjuvants (benzyl benzoate and benzyl alcohol) on the
      structure and dynamics of three Pluronic triblock copolymers (P85, P105 and F127)
      was studied using small-angle neutron scattering and pulsed-field gradient NMR.
      The two adjuvants studied have different aqueous solubilities. It was found that
      both adjuvants promoted the micellisation of the Pluronic block copolymers. In
      addition they lead to a swelling of the micelles, as shown by small-angle neutron
      scattering. From the pulsed-field gradient NMR results it was possible to
      determine the amount of adjuvant bound to the micelles.

PMID- 20129624
TI  - Seasonal postpartum hypernatremic encephalopathy with osmotic extrapontine
      myelinolysis and rhabdomyolysis.
AB  - BACKGROUND: Neurological manifestations secondary to extrapontine myelinolysis
      and rhabdomyolysis caused by hypernatremia are infrequently reported. Occurrence
      of neurological manifestations due to spontaneous hypernatremia during postpartum
      period producing rhabdomyolysis and cerebral parenchymal MRI changes has not been
      previously reported. OBJECTIVE: Evaluation of clinical and radiological profile
      of postpartum hypernatremia. METHODS: Clinical, laboratory and radiological data
      of eleven women in postpartum period presenting with hypernatremic encephalopathy
      with or without muscle weakness were reviewed. RESULTS: Eleven puerperal women
      presented with encephalopathy due to hypernatremia from 2007 to 2009.
      Consciousness was altered in all the patients ranging from confusion to deep
      coma. Nine patients had quadriparesis, eight had corticospinal and corticobulbar
      dysfunction, six had ataxia, and seizures occurred in four patients. The patients
      had hypernatremia ranging from 158 to 199mEq/l with hyperchloremia, markedly
      elevated serum CK levels (2572 to 61,107U) and azotemia. Ten patients underwent
      MRI which revealed hyperintensity of corpus callosum in all the patients in T2,
      FLAIR and diffusion weighted sequences. Symmetrical hyperintensities were seen
      also in internal capsule, corona radiata, cerebellar peduncles and hippocampus in
      various combinations. Seven patients improved neurologically with reduction of
      serum sodium and CK levels while four patients died. CONCLUSION: Hypernatremia is
      a potentially lethal condition which can produce encephalopathy, osmotic
      demyelination and rhabdomyolysis. Prompt identification and appropriate
      management can improve the outcome in these patients.

PMID- 20129625
TI  - Identification of novel and recurrent CACNA1A gene mutations in fifteen patients
      with episodic ataxia type 2.
AB  - Episodic ataxia type 2 is a rare autosomal dominant disease characterized by
      recurrent attacks of vertigo and cerebellar ataxia. The disease was caused by
      mutations in the CACNA1A gene, on chromosome 19p. We perform a mutational
      screening in a group of 43 unrelated patients. Forty-two patients presented
      episodes of disequilibrium and ataxia, and one child was studied because of the
      occurrence of episodic torticollis. The genetic analysis showed 15 mutated
      patients (35%). In 13 cases we found novel CACNA1A gene mutations, including
      missense, protein truncating, and aberrant splicing mutations. Two truncating
      mutations lead to the uppermost premature stop so far reported, challenging
      recent hypotheses on dominant negative effect. In patients without CACNA1A
      mutations, molecular testing for CACNB4 gene mutations excluded this genetic
      subtype. Clinical features of mutated subjects mostly confirmed previous sign and
      symptoms associated with EA2, including paroxysmal torticollis and mental
      retardation. CACNA1A mutated patients have an earlier age at onset, interictal
      nystagmus, and abnormalities of ocular movements. A review of all CACNA1A
      mutations so far reported showed that they are mainly located downstream exon 18.
      Our data substantially increase the number of the described CACNA1A mutations,
      and propose clinical and molecular criteria for a more focused genetic screening.

PMID- 20129626
TI  - Association of ALS with head injury, cigarette smoking and APOE genotypes.
AB  - OBJECTIVE: An increased risk of ALS has been reported for US veterans, but the
      cause is unknown. Since head injury and cigarette smoking are two previously
      implicated environmental risk factors that are more common in military than
      civilian study populations, we tested their association with ALS in a US veteran
      study population. METHODS: We used logistic regression to examine the association
      of ALS with head injury and cigarette smoking in 241 incident cases and 597
      controls. Since APOE is a plausible ALS candidate gene, we also tested its main
      effect and its statistical interaction with these environmental exposures.
      RESULTS: Cigarette smoking was not associated with ALS in this predominantly male
      and Caucasian population. Veterans who had experienced head injuries during the
      last 15years before the reference date had an adjusted odds ratio of 2.33 (95%
      confidence interval 1.18-4.61), relative to veterans without any head injuries.
      This association was strongest in APOE-4 carriers. CONCLUSIONS: Our results add
      to the body of evidence suggesting that head injuries may be a risk factor for
      multiple neurodegenerative diseases, including ALS. We hypothesize that the
      strength of association between head injuries and ALS may depend upon APOE
      genotype.

PMID- 20129627
TI  - The effect of dopamine agonists: the expression of GDNF, NGF, and BDNF in
      cultured mouse astrocytes.
AB  - In Parkinson's disease, cell death is selectively induced in mesencephalic nigral
      dopaminergic neurons. At present, no disease modifying therapy or radical
      treatment has been found for this disease. Some dopamine agonists may have a
      neuroprotective action in cultured cells and animal models. In the present study,
      we examined stimulating effects of a non-ergoline D(2) dopamine agonist,
      ropinirole, on synthesis/secretion of neurotrophic factors, including NGF, BDNF,
      and GDNF, in cultured mouse astrocytes. These effects were compared with those of
      ergoline dopamine agonists, SKF-38393, a D(1) agonist, bromocriptine, D(2)
      agonist, and apomorphine, D(1)/D(2) agonist. Ropinirole elevated GDNF levels to 4
      fold, and NGF levels to 6.3-fold, compared with the control group. Of the
      dopamine agonists examined, ropinirole produced and secreted more GDNF than a 1.8
      fold greater amount of apomorphine, a lesser amount of bromocriptine, or a 2.8
      fold greater amount of SKF-38393, which served as the control group.

PMID- 20129628
TI  - Occurrence and levels of polybrominated diphenyl ethers (PBDEs) in recent
      sediments and marine organisms from Xiamen offshore areas, China.
AB  - Surface sediments and porewater from 12 sites within Xiamen offshore areas and
      organisms from a heavily contaminated site Yuandang Lagoon were sampled and
      analyzed for eight polybrominated diphenyl ethers (PBDEs) congeners (-28, -47, 
      99, -100, -153, -154, -183 and -209). The total concentrations of eight PBDEs (
      summation operator(8)PBDEs) and BDE-209 in sediments ranged from 0.27 to
      76.54ng/g with an average of 16.31ng/g and from 0.10 to 70.11ng/g with an average
      of 14.94ng/g, respectively. Concentrations of summation operator(8)PBDEs in
      porewater ranged from 2.5 to 34.1ng/L, with a mean value of 15.3ng/L. In this
      study, the partition coefficients (log K(oc)(')) of PBDE congeners (without -209)
      were significantly correlated with their octanol-water partition coefficients
      (log K(OW)) (r(2)=0.74, P<0.01). summation operator(8)PBDE concentrations ranged
      from 0.33 to 1.26ng/g (lipid weight) in marine organisms, and PBDE congener
      patterns were significantly different between fish and clam, crab.

PMID- 20129629
TI  - The contribution of race and diabetes status to metabolic flexibility in humans.
AB  - Factors controlling metabolic flexibility (MF), the ability of the body to switch
      from fat to carbohydrate oxidation in response to feeding or with insulin
      administration, are being actively investigated. We sought to determine the
      effects of race (African American vs Caucasian) and diabetes status (nondiabetic
      vs type 2 diabetes mellitus individuals) on MF to glucose in humans. Respiratory
      quotient (RQ) and macronutrient substrate utilization were evaluated by indirect
      calorimetry during baseline (fasting) and hyperinsulinemic-euglycemic clamp
      (insulin infusion of 120 mU x m(-2) x min(-1)); DeltaRQ (MF) = clamp RQ - fasting
      RQ. The study included 168 human subjects of different races (55 African
      Americans, 113 Caucasians), sex (73 men, 95 women), ages (18-73 years), body mass
      index (19.3-47.7 kg/m(2)), and diabetes status (89 nondiabetic, 79 type 2
      diabetes mellitus subjects). Metabolic flexibility was negatively correlated (P <
      .01) with age (r = - 0.41), fasting RQ (r = -0.22), fasting glucose (r = -0.55),
      insulin (r = -0.40), and triglyceride (r = -0.44) concentrations; whereas a
      positive association was observed with insulin sensitivity (r = 0.69, P < .0001).
      Insulin sensitivity, fasting RQ, triglyceride concentrations, diabetes status,
      and race accounted for 71% of the variability in MF with insulin sensitivity
      being the main determinant factor (model R(2) = 0.48, P < .0001). After
      controlling for the significant predictors, MF was higher in African Americans vs
      Caucasians (mean +/- SEM 0.080 +/- 0.004 vs 0.069 +/- 0.002, P = .008) and in
      nondiabetic vs type 2 diabetes mellitus subjects (P = .003). This study confirms
      that insulin sensitivity is the major contributor to MF in humans, but provides
      the novel findings that African Americans have significantly greater MF than
      Caucasians even after adjusting for insulin sensitivity and diabetes status.

PMID- 20129630
TI  - Induction of acid phosphatase transcripts, protein and enzymatic activity by
      simulated herbivory of hybrid poplar.
AB  - Herbivory and wounding upregulate a large suite of defense genes in hybrid poplar
      leaves. A strongly wound- and herbivore-induced gene with high similarity to
      Arabidopsis vegetative storage proteins (VSPs) and acid phosphatase (AP) was
      identified among genes strongly expressed during the poplar herbivore defense
      response. Phylogenetic analysis showed that the putative poplar acid phosphatase
      (PtdAP1) gene is part of an eight-member AP gene family in poplar, and is most
      closely related to a functionally characterized soybean nodule AP. Unlike the
      other poplar APs, PtdAP1 is expressed in variety of tissues, as observed in an
      analysis of EST data. Following wounding, the gene shows an expression profile
      similar to other known poplar defense genes such as protease inhibitors,
      chitinase, and polyphenol oxidase. Significantly, we show for the first time that
      subsequent to the wound-induction of PtdAP1 transcripts, AP protein and activity
      increase in extracts of leaves and other tissues. Although its mechanism of
      action is as yet unknown, these results suggest in hybrid poplar PtdAP1 is likely
      a component of the defense response against leaf-eating herbivores.

PMID- 20129631
TI  - Cytosolic APx knockdown indicates an ambiguous redox responses in rice.
AB  - Ascorbate peroxidases (APX, EC 1.1.11.1) are class I heme-peroxidases, which
      catalyze the conversion of H(2)O(2) into H(2)O, using ascorbate as a specific
      electron donor. Previously, the presence of eight Apx genes was identified in the
      nuclear genome of rice (Oryza sativa), encoding isoforms that are located in
      different sub-cellular compartments. Herein, the generation of rice transgenic
      plants silenced for either both or each one of the cytosolic Apx1 and Apx2 genes
      was carried out in order to investigate the importance of cytosolic Apx isoforms
      on plant development and on plant stress responses. Transgenic double Apx1/2
      silenced plants exhibited normal development, even though these plants showed a
      global reduction of Apx activity which strongly impacts the whole antioxidant
      system regulation. Apx1/2-silenced plants also showed increased H(2)O(2)
      accumulation under control and stress situations and presented higher tolerance
      to toxic concentration of aluminum when compared to wild type plants. On the
      other hand, silencing OsApx1 and OsApx2 genes individually resulted in strong
      effect on plant development producing semi-dwarf phenotype. These results
      suggested that the double silencing of cytosolic OsApx genes induced compensatory
      antioxidant mechanisms in rice while single knockdown of these genes did not,
      which resulted in the impairing of normal plant development.

PMID- 20129632
TI  - Microtropiosides A-F: ent-Labdane diterpenoid glucosides from the leaves of
      Microtropis japonica (Celastraceae).
AB  - From a 1-BuOH-soluble fraction of a MeOH extract of the leaves of Microtropis
      japonica, collected in the Okinawa islands, six ent-labdane glucosides, named
      microtropiosides A-F, were isolated together with one known acyclic sesquiterpene
      glucoside. Their structures were elucidated by a combination of spectroscopic
      analyses, and their absolute configurations determined by application of the beta
      D-glucopyranosylation-induced shift-trend rule in (13)C NMR spectroscopy and the
      modified Mosher's method.

PMID- 20129633
TI  - Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in lactating dairy
      cows and beef steers following intravenous administration of enrofloxacin.
AB  - The comparative pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin
      were investigated in lactating cows and beef steers. The plasma elimination half
      life of either enrofloxacin or ciprofloxacin was shorter in cows than in steers.
      The overall production of ciprofloxacin was slightly higher in steers than in
      cows (metabolite ratio: 64% and 59%, respectively). There was no significant
      difference in plasma protein binding of enrofloxacin between cows (percent bound:
      59.4%) and steers (percent bound: 60.8%). Ciprofloxacin was more extensively
      bound to plasma proteins in steers (percent bound: 49.6%) than in cows (percent
      bound: 33.8%). The steady state volume of distribution of enrofloxacin is
      comparable in cows (1.55 L/kg) and steers (1.59 L/kg). Within either bovine
      class, plasma elimination half-life of enrofloxacin and ciprofloxacin are
      comparable, while plasma protein binding was higher for enrofloxacin than for
      ciprofloxacin. Ciprofloxacin was more concentrated in milk than enrofloxacin.

PMID- 20129634
TI  - Doxycycline-chloroquine vs. doxycycline-placebo for malaria prophylaxis in
      nonimmune soldiers: a double-blind randomized field trial in sub-Saharan Africa.
AB  - Failures of malaria chemoprophylaxis have been related to a lack of compliance
      with doxycycline due to its short elimination half-life. Adding a molecule with a
      long half-life to doxycycline could be useful to take over from this drug in case
      of occasional missed doses. A double-blind, placebo-controlled randomized field
      trial was designed to compare the tolerability of a doxycycline-chloroquine
      combination vs. doxycycline as malaria prophylaxis among French soldiers deployed
      in Africa. Data from 936 volunteers were analyzed. In both groups, the proportion
      of volunteers who reported at least one adverse effect was about 57%.
      Tolerability was similar in the groups except for a higher proportion of nausea
      or vomiting in the doxycycline-chloroquine group. The reported compliance rate
      was 86.6% and was similar in the two groups. Eight Plasmodium falciparum malaria
      cases were diagnosed in the doxycycline group and seven in the doxycycline
      chloroquine group. The efficacy of the two chemoprophylaxis regimens was similar.
      Our study was the first randomized field trial to assess a doxycycline
      chloroquine combination as malaria prophylaxis and showed no significant decrease
      of overall tolerability of the combination compared with doxycycline alone. Our
      results showed that a doxycycline-chloroquine combination could be a safe
      combination for malaria chemoprophylaxis.

PMID- 20129635
TI  - PCR-based detection of Leishmania major kDNA within naturally infected
      Phlebotomus papatasi in southern Iran.
AB  - The annual incidence of cutaneous leishmaniasis (CL) in Iran rose by 43% over a
      five year period, from 2002 to 2006; most of these cases were caused by
      Leishmania major. Two complementary standard and nested polymerase chain
      reactions (PCRs) were used to detect parasites within their natural vector,
      Phlebotomus papatasi. Twelve different sand fly species were morphologically
      identified. The most abundant species (31.3%) was P. papatasi. Leptomonads were
      found in nine (2.4%) phlebotomines. Twenty (5.3%) sand fly species were found
      positive for Leishmania-genus DNA using standard PCR. The infection rate of this
      species was 5% and 7% by microscopic and molecular methods, respectively.

PMID- 20129636
TI  - Successful introduction of artesunate combination therapy is not enough to fight
      malaria: results from an adherence study in Sierra Leone.
AB  - A study to measure adherence to artesunate and amodiaquine (AS+AQ) therapy in
      patients treated for uncomplicated malaria in community health centres (CHC) was
      conducted in Sierra Leone. Patients/caretakers were interviewed and remaining
      AS+AQ tablets at home after the last treatment dose were counted. Persons leaving
      CHCs with an AS+AQ prescription were also interviewed (exit interviews). In
      total, 118 patients were visited at home: 27 (22.9%) had one or more tablets left
      and were classed as certainly non-adherent; 34 (28.8%) were probably non-adherent
      [reported incorrect (n=27) or incomplete (n=7) intake]; and 57 (48.3%) were
      probably adherent. The main reasons for incomplete intake were sickness after one
      dose of AS+AQ, no food available for drug intake and forgetting to take them. For
      incorrect intake, reasons were vomiting after drug intake and incorrect
      instructions given by the CHC. Eighty-one percent of probably adherent patients
      reported following instructions given to them. In exit interviews, 82% of
      patients or caretakers of patients were able to repeat AS+AQ intake instructions
      correctly. Adherence to antimalarial treatment should not be taken for granted.
      Instructions on correct AS+AQ use should include discussion of disease symptoms
      as well as possible treatment side effects and how to manage them. Other factors
      are more difficult to influence, such as patients forgetting to take the
      treatment.

PMID- 20129637
TI  - Identification of N-linked carbohydrates from severe acute respiratory syndrome
      (SARS) spike glycoprotein.
AB  - N-glycans were released from the SARS coronavirus (SARS-CoV) spike glycoprotein
      produced in Vero E6 cells and their structures were determined by a combination
      of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry,
      negative ion electrospray collision-induced dissociation time-of-flight mass
      spectrometry and normal-phase high-performance liquid chromatography with
      exoglycosidase digestion. Major glycans were high-mannose (Man(5-9)GlcNAc(2)),
      hybrid and bi-, tri- and tetra-antennary complex with and without bisecting
      GlcNAc and core fucose. Complex glycans with fewer than the full complement of
      galactose residues were present and sialylation was negligible. Treatment with
      the glucosidase inhibitor N-butyl-deoxynojirimycin (NB-DNJ) inhibited N-glycan
      processing as evidenced by the appearance of glycans of composition Glc(3)Man(7
      9)GlcNAc(2). However, some complex glycans remained suggesting the presence of an
      alpha-endomannosidase. Our data in tissue culture indicate that inhibition of N
      glycan processing may be considered as a therapeutic strategy against SARS CoV
      infections.

PMID- 20129638
TI  - Mucosal parainfluenza virus-vectored vaccine against Ebola virus replicates in
      the respiratory tract of vector-immune monkeys and is immunogenic.
AB  - We previously used human parainfluenza virus type 3 (HPIV3) as a vector to
      express the Ebola virus (EBOV) GP glycoprotein. The resulting HPIV3/EboGP vaccine
      was immunogenic and protective against EBOV challenge in a non-human primate
      model. However, it remained unclear whether the vaccine would be effective in
      adults due to preexisting immunity to HPIV3. Here, the immunogenicity of
      HPIV3/EboGP was compared in HPIV3-naive and HPIV3-immune Rhesus monkeys. After a
      single dose of HPIV3/EboGP, the titers of EBOV-specific serum ELISA or
      neutralization antibodies were substantially less in HPIV3-immune animals
      compared to HPIV3-naive animals. However, after two doses, which were previously
      determined to be required for complete protection against EBOV challenge, the
      antibody titers were indistinguishable between the two groups. The vaccine virus
      appeared to replicate, at a reduced level, in the respiratory tract despite the
      preexisting immunity. This may reflect the known ability of HPIV3 to re-infect
      and may also reflect the presence of EBOV GP in the vector virion, which confers
      resistance to neutralization in vitro by HPIV3-specific antibodies. These data
      suggest that HPIV3/EboGP will be immunogenic in adults as well as children.

PMID- 20129639
TI  - Interferon regulatory factor (IRF)-2 activates the HPV-16 E6-E7 promoter in
      keratinocytes.
AB  - Interferon regulatory factors (IRFs) are critical mediators of gene expression,
      cell growth and immune responses. We previously demonstrated that interferon
      (IFN) induction of early viral transcription and replication in several mucosal
      HPVs requires IRF-1 binding to a conserved interferon response element (IRE).
      Here we show that the IRF-2 protein serves as a baseline transactivator of the
      HPV-16 major early promoter, P97. Cotransfections in IRF knockout cells confirmed
      that basal HPV-16 promoter activity was supported by both IRF-1 and IRF-2
      complexes interacting with the promoter-proximal IRE in a dose-dependent manner.
      Furthermore, HPV-16 E7 expression downregulates the IRF-2 promoter, thus linking
      IRF-2 levels to viral transforming gene expression through a negative feedback
      mechanism. Taken together, these observations reveal a complex viral strategy
      utilizing multiple signal transduction pathways during the establishment and
      maintenance of HPV persistence.

PMID- 20129640
TI  - Modeling the UV/hydrogen peroxide advanced oxidation process using computational
      fluid dynamics.
AB  - The use of numerical models for the design and optimization of UV/H(2)O(2)
      systems must incorporate both reactor design (hydrodynamics, lamp orientation)
      and chemical kinetics (reaction mechanisms, kinetic rate constants). This study
      was conducted to evaluate the performance of comprehensive CFD/UV/AOP models for
      the degradation of an indicator organic contaminant. The combination of
      turbulence sub-models, fluence rate sub-models, and kinetic rate equations
      resulted in a comprehensive and flexible design tool for predicting the effluent
      chemical composition from a UV-initiated AOP reactor. The CFD model tended to
      under predict the percent removal of methylene blue compared to pilot reactor
      trials under the same operating conditions. In addition, the percent difference
      between the pilot and the CFD results increased with increasing flow rates. The
      MSSS fluence rate sub-model predicted higher contaminant removal values than the
      RAD-LSI sub-model while the different two-equation turbulence sub-models did not
      significantly impact the predicted removal for methylene blue in the tested
      reactor configuration. The overall degradation of methylene blue was a strong
      function of the second-order kinetic rate constant describing the reaction
      between methylene blue and the hydroxyl radical. In addition, the removal of
      methylene blue was sensitive to the concentration of dissolved organic carbon in
      the water matrix since DOC acts as a scavenger of hydroxyl radicals.

PMID- 20129641
TI  - Ultrasonic extraction of arsenic and selenium from rocks associated with
      mountaintop removal/valley fills coal mining: Estimation of bioaccessible
      concentrations.
AB  - Ultrasonic extraction (UE) was used to estimate the total bioaccessible fractions
      of arsenic and selenium released from rocks associated with mountaintop
      removal/valley fill coal mining. The combined readily bioaccessible amounts of
      arsenic and selenium in water soluble, exchangeable and NaOH fractions can be
      extracted from the solid phase within a 20 or 25 min application of 200 W cm(-2)
      ultrasound energy in nanopure water for selenium and arsenic, respectively.
      Application of a two-way ANOVA predicted that there are no significant
      differences (p0.001, n=12) in the extracted arsenic and selenium concentrations
      between the combined bioaccessible and ultrasonic extracts. The mechanisms for
      the UE of arsenic and selenium are thought to involve the formation of secondary
      minerals on the particle surfaces which eventually dissolve with continued
      sonication. This is supported by the presence of transient Si-O stretching and OH
      absorption and bending ATR-FTIR peaks at 795.33 cm(-1), 696.61 cm(-1) and 910.81
      cm(-1). The subsequent dissolution of secondary minerals is followed by the
      release of chemical species that include selenium and arsenic. Release rates
      decrease after the ultrasound energy elastic limit for the particles is reached.
      Selenium and arsenic are bound differently within the rock lattice because no
      selenium was detected in the acid soluble fraction and no arsenic was found in
      the exchangeable fraction. However, selenium was found in the exchangeable
      fraction and arsenic was found in the acid soluble fraction. The characterization
      of coal associated rocks is essential to the design of methodologies and
      procedures that can be used to control the release of arsenic and selenium from
      valley fills.

PMID- 20129642
TI  - Microwave-assisted hydrolysis of nitroglycerin (NG) under mild alkaline
      conditions: new insight into the degradation pathway.
AB  - Nitroglycerin (NG), a nitrate ester, is widely used in the pharmaceutical
      industry and as an explosive in dynamite and as propellant. Currently NG is
      considered as a key environmental contaminant due to the discharge of wastewater
      tainted with the chemical from the military and pharmaceutical industry. The
      present study describes hydrolytic degradation of NG (200 microM) at pH 9 using
      either conventional or microwave-assisted heating at 50 degrees C. We found that
      hydrolytic degradation of NG inside the microwave chamber was much higher than
      its degradation using conventional heating. Products distributions in both
      heating systems were closely related and included nitrite, nitrate, formic acid,
      and the novel intermediates 2-hydroxypropanedial (OCHCH(OH)HCO) and glycolic acid
      (CH2(OH)COOH). Two other intermediates glycolaldehyde (CH2(OH)CHO) and glyoxylic
      acid (CHOCOOH) were only detected in the microwave treated samples. The molar
      ratio of nitrite to nitrate in the presence and absence of microwave heating was
      2.5 and 2.8, respectively. In both microwave assisted and conventional heating a
      nitrogen mass balance of 96% and 98% and a carbon mass balance of 58% and 78%,
      respectively, were obtained. The lower C mass recovery might be attributed to
      further unknown reactions, e.g., polymerization of the aldehydes CH2(OH)CHO,
      CHOCOOH and OCHCH(OH)HCO. A hydrolytic degradation pathway for NG was proposed
      involving denitration (loss of 2 NO2(-)) from the two primary carbons and the
      loss of one nitrate from the secondary carbon to produce 2-hydroxypropanedial.

PMID- 20129643
TI  - Assessing the effects of FBC ash treatments of metal-contaminated soils using
      life history traits and metal bioaccumulation analysis of the earthworm Eisenia
      andrei.
AB  - Earthworms (Eisenia andrei) were exposed, in controlled conditions, to metal
      contaminated soils previously treated in situ with two types of fluidized bed
      combustion ashes. Effects on this species were determined by life history traits
      analysis. Metal immobilizing efficiency of ashes was indicated by metal
      bioaccumulation. Ashes-treated soils reduced worm mortality compared to the
      untreated soil. However, these ashes reduced both cocoon hatching success and
      hatchlings numbers compared to the untreated soil. In addition, sulfo-calcical
      ashes reduced or delayed worm maturity and lowered cocoon production compared to
      silico-alumineous ones. Metal immobilizing efficiency of ashes was demonstrated
      for Zn, Cu and to a lesser extent Pb. Only silico-alumineous ashes reduced Cd
      bioaccumulation, although Cd was still bioconcentrated. Thus, although ash
      additions to metal-contaminated soils may help in immobilizing metals, their use
      might result, depending on the chemical nature of ashes, to severe detrimental
      effects on earthworm reproduction with possible long term consequences to
      populations.

PMID- 20129644
TI  - Assessment of dietary furan exposures from heat processed foods in Taiwan.
AB  - Furan has been demonstrated to be formed in a variety of heat processed foods.
      The presence of furan is of potential health concern because it has been
      classified as 'possibly carcinogenic to humans' by the International Agency for
      Research on Cancer (IARC). To assess the associate risks from possible exposures
      in Taiwan, headspace solid-phase microextraction (HS-SPME) coupled with gas
      chromatography/mass spectrometer (GC/MS) was used to determine furan in a variety
      of food samples. Due to matrix effects, standard addition method was selected to
      be performed in this study. More than 100 processed foods were analyzed, and the
      results showed that the concentrations of furan ranged from 0.4ngg(-1) to 150ngg(
      1) in various kinds of samples. Higher furan levels were found principally in the
      categories of baby foods, coffees, sauces and broths. Exposures from different
      food varieties were also estimated. As for adults in Taiwan, the average daily
      intakes of furan were estimated to be 299.89ngkg(-1) body weight d(-1) for male,
      and 177.18ngkg(-1) body weight d(-1) for female. For a 6-month-old baby, the
      daily intake was estimated to be 0.05-0.56, and 0.11-3.42microgkg(-1) body weight
      d(-1) from infant formula and baby food, respectively. To avoid possible
      exposure, safety precautions such as heating in an open can and applying stirring
      are recommended to lower the furan level in foods.

PMID- 20129645
TI  - Prognostic role of beta-catenin and p53 expression in the metastatic progression
      of sporadic colorectal cancer.
AB  - Beta-catenin and p53 play key roles in tumorigenesis. The relationships between
      these 2 signaling pathways and their contribution to colorectal cancer metastatic
      progression have not been completely elucidated. We analyzed 141 cases of primary
      sporadic colorectal cancer, 45 matched metastases, and 80 samples of normal
      mucosa by immunohistochemistry on paraffin-embedded specimens. The expression
      profiles were also related to patients' clinicopathologic features and 5-year
      survival. In primary tumors, beta-catenin immunoreactivity was nuclear (27%),
      predominantly membrane/cytosolic (46.0%) or negative (27%). This latter subgroup
      was strongly related to microsatellite instability, in particular to MLH-1
      deficiency. Remarkably, beta-catenin membrane/cytosolic expression in primary
      tumors was reduced in the corresponding matched metastases. p53 showed a
      significant increase in immunoreactivity in (66.7%), whereas it was negative in
      (33.3%) of tumors. When we considered the expression of both genes, the
      combination of negative beta-catenin and positive p53 nuclear staining (21%) was
      strongly related to a higher frequency of liver metastases. Such an association
      was significantly related to a worse prognosis than any other combination. In a
      multivariate analysis, beta-catenin and distant metastases were independent
      prognostic markers. We suggest that a combination of low beta-catenin and high
      p53 expression in primary colorectal cancers may be a prognostic factor in
      predicting the progression of the disease, the occurrence of metastasis, and a
      more severe outcome.

PMID- 20129646
TI  - Creation of a fully digital pathology slide archive by high-volume tissue slide
      scanning.
AB  - Digital slide scanners for scanning glass slides are becoming increasingly
      popular because current scanners are fast enough and produce good enough images
      for diagnostic purposes, education, and research. Also, the price for storing
      vast amounts of data has decreased over the last years, and this trend is
      expected to continue. Where most laboratories use their scanners mainly for
      education and research with limited financial and technical implications, we
      decided to face the huge challenges of prospectively setting up a fully digital
      pathology slide archive, primarily aiming to optimize the preparation and running
      of clinicopathological conferences. In this article, we describe the setup of our
      digital archiving solution and discuss the technical challenges we had to
      overcome. To give insight in the performance of our digital archive, we provide
      some statistics as well. We also present our thoughts on future developments in
      the area of digital slide scanning.

PMID- 20129647
TI  - Profile storage of organic/inorganic carbon in soil: from forest to desert.
AB  - Understanding the distribution of organic/inorganic carbon storage in soil
      profile is crucial for assessing regional, continental and global soil C stores
      and predicting the consequences of global change. However, little is known about
      the organic/inorganic carbon storages in deep soil layers at various landscapes.
      This study was conducted to determine the soil organic/inorganic carbon storage
      in soil profile of 0-3m at 5 sites of natural landscape from forest to desert.
      Landscapes are temperate forest, temperate grassland, temperate shrub-grassland,
      temperate shrub desert, and temperate desert. Root mass density and carbon
      contents at the profile were determined for each site. The results showed that
      considerable decrease in root biomass and soil organic carbon content at the soil
      profile of 0-3m when landscape varied from forest to desert along a precipitation
      gradient, while soil inorganic carbon content increased significantly along the
      precipitation gradient. Namely, for density of soil organic carbon:
      forest>grassland>shrub-grassland>shrub desert>desert; for density of soil
      inorganic carbon: forest, grassland<shrub-grassland<shrub desert<desert (P<0.05
      in all cases). In landscapes other than forest, more than 50% soil carbon storage
      was found in 1-3m depth. For grassland and shrub-grassland, the contribution from
      1-3m was mainly in the form of organic carbon, while for shrub desert and desert
      the contribution from this depth was mainly in the form of inorganic carbon. The
      comparison of soil C storage between top 0-1m and 1-3m showed that the using top
      1m of soil profile to estimate soil carbon storages would considerably
      underestimate soil carbon storage. This is especially true for organic soil
      carbon at grassland region, and for soil inorganic carbon at desert region.

PMID- 20129648
TI  - Errors and misunderstandings invalidate estimates of titanium dioxide inhalation
      risk.

PMID- 20129650
TI  - Relationship between platelet reactivity inhibition and non-CABG related major
      bleeding in patients undergoing percutaneous coronary intervention.

PMID- 20129649
TI  - Protein-phospholipid interactions in blood clotting.
AB  - Most steps of the blood clotting cascade require the assembly of a serine
      protease with its specific regulatory protein on a suitable phospholipid bilayer.
      Unfortunately, the molecular details of how blood clotting proteins bind to
      membrane surfaces remain poorly understood, owing to a dearth of techniques for
      studying protein-membrane interactions at high resolution. Our laboratories are
      tackling this question using a combination of approaches, including nanoscale
      membrane bilayers, solid-state NMR, and large-scale molecular dynamics
      simulations. These studies are now providing structural insights at atomic
      resolution into clotting protein-membrane interactions.

PMID- 20129651
TI  - Relationship between down-regulation of HIC1 and PTEN genes and dysfunction of
      pancreatic islet cells in diabetic rats.
AB  - The aim of the study was to investigate the protein expression of hypermethylated
      in cancer 1 (HIC1 ) and phosphatase and tensin homologue (PTEN) genes and to
      study their mRNA expressions in normal and diabetic pancreatic islet cells in
      rats in order to try and identify the functions of these genes in the development
      and advancement of diabetes. We further aimed to analyze the expression of
      mammalian target of rapamycin (mTOR), which is regulated by PTEN and to
      investigate the possible mechanism of PTEN affecting the function of diabetic
      islet cells. The expressions of HIC1, PTEN and mTOR genes were examined in the
      pancreatic islets of 20 normal male Wistar rats and 47 diabetic male Wistar rats
      by immunohistochemistry, Western blot, RT-PCR and real-time RT-PCR. Results
      showed that expressions of HIC1 and PTEN in protein and mRNA levels were lower in
      pancreatic islets of diabetic rats than in normal rats. Expressions of mTOR in
      protein and mRNA levels were higher in pancreatic islets of diabetic rats than in
      the normal rats. Marked apoptosis of pancreatic islet cells was observed in 29
      cases (29/47, 61.7%) in diabetic rats, but not in the remaining 18 (18/47, 38.3%)
      diabetic rats. The down-regulation of HIC1 and PTEN and up-regulation of mTOR in
      protein and mRNA level are positively correlated with functional impairment of
      islet cells in diabetic rats. From this study we conclude that HIC1, PTEN and
      mTOR cannot be recognized as the key influencing factors promoting pancreatic
      islet cells apoptosis of diabetic rats; however, lower expressions of HIC1 and
      PTEN and higher expression of mTOR may affect the function of the pancreatic
      islet cells in diabetic rats.

PMID- 20129652
TI  - Long-term cervical cancer prevention strategies across the globe.
AB  - Worldwide, there are several approaches for the prevention of cervical cancer,
      and in the near future it is likely that human papillomavirus (HPV) vaccination
      and HPV-based screening will be complementary strategies. In the US, professional
      guidelines on HPV screening recommend a co-testing approach utilizing HPV DNA
      testing and cytology in women aged >=30 years. However, a growing body of
      evidence indicates that HPV testing is more sensitive than cytology, suggesting
      that HPV DNA testing may be more useful as the sole primary screening modality,
      especially for newly implemented programs. HPV vaccination programs targeted at
      young girls have been widely implemented in several affluent countries, and
      currently available data confirm the long-term efficacy of the VLP-based vaccines
      against HPV-related disease over periods of up to 8 years. If these HPV vaccines
      continue to demonstrate sustained and durable efficacy, less frequent screening
      may become a reality, but screening will continue to play an important role in
      providing protection for disease caused by types not included in these vaccines.
      However, a significant HPV vaccination-induced reduction in cervical cancer
      burden is not likely to be realized for at least 10 to 15 years.

PMID- 20129653
TI  - HPV vaccine and males: issues and challenges.
AB  - The quadrivalent vaccine has been shown to be safe and efficacious against HPV
      infection in men. It is expected, though, that male vaccination rates will remain
      low. Therefore this literature review examines the attitudes of parents, young
      men, and HCPs toward HPV vaccination and other sexually transmitted infections
      (STI). It appears that parents are interested in vaccinating their sons against
      HPV and other (STI). In addition, adolescent and adult males are interested in
      receipt of HPV vaccine and other vaccines for prevention of STI. Health care
      providers have a general preference for vaccinating females, but they indicate a
      willingness to recommend HPV vaccine for their male patients. This is important
      given the "permissive" recommendation for male HPV vaccination issued by the US
      Advisory Committee on Immunization Practices (ACIP). Cost effectiveness studies
      have shown that vaccinating males and females is less cost effective than
      vaccinating females alone. With low female vaccination rates, both cost
      effectiveness and health benefits increase. It is clear that males have poor
      knowledge of HPV infection, morbidity, transmission and prevention. Regardless of
      vaccination strategies adopted, efforts should be made to educate males about HPV
      and its health implications. In addition, there are more challenges to overcome
      before male vaccination can be successfully implemented.

PMID- 20129654
TI  - Global implementation of human papillomavirus (HPV) vaccine: lessons from
      hepatitis B vaccine.
AB  - Development of safe and effective vaccines against human papillomavirus (HPV)-the
      second vaccine against a major human cancer-is one of the most important medical
      and public health achievements of this century. As with all new vaccines, HPV is
      currently expensive and this cost precludes its use in the developing world,
      which has the greatest burden of disease from HPV-related cancers. Hepatitis B
      (HB) virus vaccine, which prevents chronic HB infection and related cirrhosis and
      liver cancer, has been successfully introduced as a routine vaccine for children
      in 89% of countries, including the poorest. The success of this vaccine provides
      a model for the introduction of HPV vaccine and control of cervical and other HPV
      related cancers and genital warts. Lessons learned from HB vaccine introduction
      are relevant to our efforts to introduce HPV vaccine globally. As with HB
      vaccine, introduction of HPV vaccine into national immunization programs and
      routine use of this vaccine, funded by governments, will be needed to control HPV
      related disease on a global basis. Global funding support will be needed to make
      control a reality for the poorest countries, and the program to accomplish this,
      the Global Alliance for Vaccines and Immunization (GAVI), has already expressed
      great interest in including HPV vaccine. For this to occur, the manufacturers
      will need to dramatically reduce the vaccine price for the poorest developing
      countries, and tier prices for wealthier developing countries not eligible for
      GAVI support. Countries will need to decide on the priority of HPV control in the
      context of other important new vaccines against pneumococcal pneumonia and
      rotavirus diarrhea.

PMID- 20129655
TI  - Experimental models in animal reproduction: theoretical and practical approaches.
      Preface.

PMID- 20129656
TI  - Intrauterine inoculation of seronegative heifers with bovine viral diarrhea virus
      concurrent with transfer of in vivo-derived bovine embryos.
AB  - Bovine viral diarrhea virus (BVDV) has been shown to be associated with single
      transferable in vivo-derived bovine embryos despite washing and trypsin
      treatment. Hence, the primary objective was to evaluate the potential of BVDV to
      be transmitted via the intrauterine route at the time of embryo transfer. In vivo
      derived bovine embryos (n=10) were nonsurgically collected from a single Bos
      tarus donor cow negative for BVDV. After collection and washing, embryos were
      placed into transfer media containing BVDV (SD-1; Type 1a). Each of the 10
      embryos was individually loaded into an 0.25-mL straw, which was then
      nonsurgically transferred into the uterus of 1 of the 10 seronegative recipients
      on Day 0. The total quantity of virus transferred into the uterus of each of the
      10 Bos tarus recipients was 878 cell culture infective doses to the 50% end point
      (CCID(50))/mL. Additionally, control heifers received 1.5 x 10(6) CCID(50)
      BVDV/.5 mL without an embryo (positive) or heat-inactivated BVDV (negative). The
      positive control heifer and all 10 recipients of virus-exposed embryos exhibited
      viremia by Day 6 and seroconverted by Day 15 after transfer. The negative control
      heifer did not exhibit a viremia or seroconvert. At 30 d after embryo transfer, 6
      of 10 heifers in the treatment group were pregnant; however, 30 d later, only one
      was still pregnant. This fetus was nonviable and was positive for BVDV. In
      conclusion, the quantity of BVDV associated with bovine embryos after in vitro
      exposure can result in viremia and seroconversion of seronegative recipients
      after transfer into the uterus during diestrus.

PMID- 20129657
TI  - Ability of sulfated glycoconjugates and disulfide-reductants to release bovine
      epididymal sperm bound to the oviductal epithelium in vitro.
AB  - In Bos taurus, at ejaculation, epididymal sperm acquire a number of proteins
      secreted in the seminal plasma that increase their ability to interact with the
      female reproductive tract. Sperm-oviduct interaction comprises a transient sperm
      adhesion to the isthmus, the lower portion of the oviduct, followed by sperm
      release around ovulation. Oviductal fluid molecules, such as sulfated
      glycoconjugates and disulfide-reductants, are able to release bovine ejaculated
      sperm bound to the oviductal epithelium in vitro through the reduction of sperm
      surface protein disulfides to sulfhydryls. To understand whether the sperm
      molecules sensitive to releasing signals are already exposed on the surface of
      epididymal sperm, we studied the ability of cauda epididymal sperm to adhere to
      the oviductal epithelium and to be released by sulfated glycoconjugates and the
      disulfide-reductant penicillamine. Surface protein sulfhydryls in cauda
      epididymal sperm were analyzed in the initial suspension, in sperm bound to the
      in vitro-cultured oviductal epithelium, and in released sperm. Results showed
      that epididymal sperm are able to bind the oviductal epithelium in vitro,
      although at a lower extent than frozen-thawed ejaculated sperm; the interaction
      is mediated by oviductal cell microvilli that closely bind to the plasma membrane
      of the sperm head rostral region, as previously shown for ejaculated sperm. The
      sulfated glycoconjugates heparin, fucoidan, and dextran sulfate, as well as the
      disulfide-reductant penicillamine, are all powerful inducers of sperm release.
      The level of sulfhydryls in sperm surface proteins was (1) high in the initial
      sperm suspension; (2) low in bound sperm; (3) markedly increased in sperm
      released by heparin or by penicillamine. In conclusion, epididymal sperm are
      already able to bind the oviductal epithelium and to respond to the inducers of
      release through the reduction of sperm surface protein disulfides to sulfhydryls.

PMID- 20129658
TI  - The influence of family relations on trajectories of cigarette and alcohol use
      from early to late adolescence.
AB  - The present study examines growth curve trajectories of cigarette and alcohol use
      from 13 to 19 years, and investigates how family relations (i.e., decision-making
      opportunities, negative family interactions, and positive identification with
      parents) relate to contemporaneous and predictive alcohol and cigarette use
      during adolescence. Data came from a longitudinal study of European American and
      African American families from a range of socioeconomic backgrounds (n = 1160 for
      alcohol use; n = 1102 for cigarette use). European Americans had higher levels
      and faster rates of alcohol and cigarette use than African Americans. European
      Americans females had the greatest likelihood of increased cigarette use.
      Negative family interactions and positive identification had contemporaneous and
      predictive associations with alcohol and/or cigarette use. Negative family
      interactions were related to increased smoking and drinking, whereas positive
      identification was associated with decreased use. Family relations differentially
      affected cigarette use according to ethnicity and gender, but had similar effects
      on alcohol use.

PMID- 20129659
TI  - Trace organic contaminants and their sources in surface sediments of Santa Monica
      Bay, California, USA.
AB  - Spatial distribution of selected contaminants in the surface sediments of Santa
      Monica Bay (SMB), California was investigated. Sediments were analyzed for DDTs
      (DDT and metabolites), polychlorinated biphenyls (PCBs), polycyclic aromatic
      hydrocarbons (PAHs), linear alkylbenzenes (LABs) and coprostanol. Effluent
      samples from the Hyperion Treatment Plant (HTP), which discharges treated
      municipal wastewater effluents into SMB, were also analyzed. The inter
      correlation in the distribution trends of contaminants was examined. The
      concentrations of contaminants were interpolated in a geographic information
      system to visualize their spatial distribution in the Bay. Inventories of the
      contaminants were also estimated. The concentrations of coprostanol, LABs and
      PCBs are very high only in the vicinity of the sewage outfall whereas PAHs and
      DDTs occur widespread in the Bay. The poor correlation of DDTs with LABs, PAHs or
      coprostanol content confirms the historic origin of DDTs and their absence in the
      contemporary wastewaters. Moderate correlation of DDTs with PCBs implies historic
      deposits as a major origin of PCBs. There are hot spots of DDTs at water depths
      of 60 and 100m and the inventory of DDTs in Bay sediments is insignificant
      compared to that estimated in the Palos Verdes Shelf which extends from the
      southern edge of Redondo Canyon around Palos Verdes Peninsula. The concentration
      of toxic contaminants was examined according to published sediment quality
      guidelines. About 20 stations contain p, p'-DDE and/or total DDTs above ERM and,
      PCBs between ERL and ERM indicating potential for adverse biological effects.

PMID- 20129660
TI  - A mixture model for water uptake, degradation, erosion and drug release from
      polydisperse polymeric networks.
AB  - We introduce a general class of mixture models suitable to describe water
      dependent degradation and erosion of biodegradable polymers in conjunction with
      drug release. The ability to predict and quantify degradation and erosion has
      direct impact in a variety of biomedical applications and is a useful design tool
      for biodegradable implants and tissue engineering scaffolds. The model is based
      on a finite number of constituents describing the polydisperse polymeric system,
      each representing chains of an average size, and two additional constituents,
      water and drug. Hydrolytic degradation of individual chains occurs at the
      molecular level and mixture constituents diffuse individually accordingly to
      Fick's 1st law at the bulk level - such analysis confers a multi-scale aspect to
      the resulting reaction-diffusion system. A shift between two different types of
      behavior, each identified to surface or bulk erosion, is observed with the
      variation of a single non-dimensional parameter measuring the relative importance
      of the mechanisms of reaction and diffusion. Mass loss follows a sigmoid decrease
      in bulk eroding polymers, whereas decreases linearly in surface eroding polymers.
      Polydispersity influences degradation and erosion of bulk eroding polymers and
      drug release from unstable surface eroding matrices is dramatically enhanced in
      an erosion-controlled release.

PMID- 20129661
TI  - The effects of Runx2 immobilization on poly (epsilon-caprolactone) on osteoblast
      differentiation of bone marrow stromal cells in vitro.
AB  - In vivo regenerative gene therapy is a promising approach for bone regeneration
      and can help to address cell-source limitations through surgical implantation of
      osteoinductive materials and subsequent recruitment of host-derived cells.
      Localized viral delivery may reduce the risk of virus dispersion, enhance
      transduction efficiency, and reduce administration/injection dosing, which
      subsequently increases patient safety. In this manuscript, we present a custom
      tailored strategy to immobilize adenovirus expressing runt-related transcription
      factor 2 (AdRunx2) by using reactive polymer coatings to enhance in vitro
      osteoblast differentiation of bone marrow stromal cells (BMSCs). A thin polymer
      film of poly[p-xylylene carboxylic acid pentafluorophenol ester-co-p-xylylene]
      equipped with amine-reactive active ester groups was deposited on the surface of
      poly (epsilon-caprolactone) (PCL) using the chemical vapor deposition (CVD)
      polymerization technique and then anti-adenovirus antibody was conjugated on the
      material with an amide chemical bond. Following antibody conjugation, AdRunx2 was
      conjugated to the PCL surface through antibody-antigen interaction. Osteoblast
      differentiation of BMSCs was induced by incubation in osteogenic medium. Alkaline
      phosphatase (ALP) activity, calcium deposition, and matrix mineralization were
      confirmed as markers of osteoblast formation. Incubation of the BMSCs in the
      presence of AdRunx2 modified PCL resulted in a 6.5-fold increase in ALP activity
      and significant increases in matrix mineralization when compared to controls.
      These results demonstrate that adenovirus vectors driving the expression of
      transcription factors can be delivered directly from biomaterials to direct cell
      differentiation.

PMID- 20129662
TI  - The effect of a single remote injection of statin-impregnated poly (lactic-co
      glycolic acid) microspheres on osteogenesis around titanium implants in rat
      tibia.
AB  - The aim of this study was to evaluate the effects of newly developed injectable
      poly (lactic-co-glycolic acid) (PLGA) microspheres containing fluvastatin on
      osteogenesis around titanium implants in the rat tibia. After confirmation of the
      sustained-release profile of fluvastatin from the microspheres by an in vitro
      assay, the microspheres were administered to the back skin of the rats by a
      single transdermal injection. At 2 and 4 weeks after the implant surgery, the
      fluvastatin groups showed enhanced new bone formation around the titanium
      implants without any influence on the serum biochemistry. In addition, the
      fluvastatin groups showed increased three-point bending strengths of their
      femurs. The results of this study indicate that a single remote injection of
      PLGA/fluvastatin microspheres safely and successfully stimulated bone formation
      around titanium implants and increased the mechanical properties of bone.

PMID- 20129664
TI  - Review: LIF and IL11 in trophoblast-endometrial interactions during the
      establishment of pregnancy.
AB  - Blastocyst implantation into the endometrium is critical for the establishment of
      pregnancy and is tightly regulated by factors within the blastocyst-endometrial
      micro-environment. Implantation is a continuum involving blastocyst adhesion to
      the endometrial epithelium followed by trophoblast penetration of the epithelium.
      The trophoblast proliferates and invades through the endometrium, with a
      subpopulation acting to remodel the spiral arteries. Trophoblast-endometrial
      interactions in humans involve carefully orchestrated temporal and spatial
      alterations in factors that are critical for pregnancy success. Emerging evidence
      suggests important roles for locally produced cytokines including interleukin 11
      and leukemia inhibitory factor in the various stages of implantation. This review
      focuses on the role of these cytokines in trophoblast-endometrial interactions
      during the establishment of human pregnancy.

PMID- 20129663
TI  - A 3-D cardiac muscle construct for exploring adult marrow stem cell based
      myocardial regeneration.
AB  - Adult bone marrow stromal cells (BMSCs) are capable of differentiating into
      cardiomyocyte-like cells in vitro and contribute to myocardial regeneration in
      vivo. Consequently, BMSCs may potentially play a vital role in cardiac repair and
      regeneration. However, this concept has been limited by inadequate and
      inconsistent differentiation of BMSCs into cardiomyocytes along with poor
      survival and integration of neo-cardiomyocytes after implantation into ischemic
      myocardium. In order to overcome these barriers and to explore adult stem cell
      based myocardial regeneration, we have developed an in vitro model of three
      dimensional (3-D) cardiac muscle using rat ventricular embryonic cardiomyocytes
      (ECMs) and BMSCs. When ECMs and BMSCs were seeded sequentially onto a 3-D tubular
      scaffold engineered from topographically aligned type I collagen-fibers and
      cultured in basal medium for 7, 14, 21, or 28 days, the maturation and co
      differentiation into a cardiomyocyte lineage was observed. Phenotypic induction
      was characterized at morphological, immunological, biochemical and molecular
      levels. The observed expression of transcripts coding for cardiomyocyte
      phenotypic markers and the immunolocalization of cardiomyogenic lineage
      associated proteins revealed typical expression patterns of neo-cardiomyogenesis.
      At the biochemical level differentiating cells exhibited appropriate metabolic
      activity and at the ultrastructural level myofibrillar and sarcomeric
      organization were indicative of an immature phenotype. Our 3-D co-culture system
      sustains the ECMs in vitro continuum of differentiation process and
      simultaneously induces the maturation and differentiation of BMSCs into
      cardiomyocyte-like cells. Thus, this novel 3-D co-culture system provides a
      useful in vitro model to investigate the functional role and interplay of
      developing ECMs and BMSCs during cardiomyogenic differentiation.

PMID- 20129665
TI  - Aldosterone and cortisol acutely stimulate Na+/H+ exchanger activity in the
      syncytiotrophoblast of the human placenta: effect of fetal sex.
AB  - Na(+)/H(+) exchanger (NHE) activity regulates intracellular pH (pH(i)) in the
      placental syncytiotrophoblast. In other tissues aldosterone and cortisol have
      been shown to up-regulate NHE activity via an acute, non-genomic effect. Here we
      tested the hypothesis that these corticosteroids stimulate NHE in the
      syncytiotrophoblast. Villous fragments from term placentas were loaded with 1 muM
      BCECF (pH sensitive fluorescent dye) and the syncytiotrophoblast acidified with a
      pre-pulse of 20 mM NH(4)Cl. The Na(+)-dependent recovery of pH(i) from this acid
      load was taken as a measure of NHE activity (pH units/sec, mean +/- SEM, n =
      number of placentas). In placental villi from female babies aldosterone
      significantly increased the rate of recovery of pH(i) from an acid load (0.0087
      +/- 0.0005 versus 0.0056 +/- 0.0009 pH units/s, n = 8 p < 0.05 Paired Student's t
      test) which was inhibited by the mineralocorticoid receptor antagonist,
      spironolactone (1 microM) but not the glucocorticoid antagonist mifepristone (1
      microM). There was no effect on the rate of recovery from an acid load in villi
      from placenta from male babies. Alone, neither cortisol (1 microM, n = 5) nor
      carbenoxolone (100 microM, n = 9), an inhibitor of 11-beta-hydroxysteroid
      dehydrogenase-2 (11-beta-HSD-2), altered the rate of recovery from an acid load.
      However, simultaneous application of cortisol with carbenoxolone significantly
      increased the rate of recovery from an acid load but again only in placentas from
      female babies (0.0080 +/- 0.0017 versus control 0.0037 +/- 0.0005, p < 0.05 pH
      units/s, n = 9 Paired Student's t-test). Stimulation by cortisol in female tissue
      was inhibited by mifepristone but not spironolactone. In conclusion,
      syncytiotrophoblast NHE activity is increased acutely by aldosterone and, when 11
      beta-HSD-2 is blocked, by cortisol. These non-genomic effects are only evident in
      placentas from female babies and are mediated by classical mineralocorticoid
      and/or glucocorticoid receptors.

PMID- 20129666
TI  - L-beta-ODAP alters mitochondrial Ca2+ handling as an early event in
      excitotoxicity.
AB  - The neurotoxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (L-beta-ODAP) is
      an L-glutamate analogue at alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid (AMPA)/kainate receptors in neurons and therefore acts as an excitotoxic
      substance. Chronic exposure to L-beta-ODAP present in Lathyrus sativus L. (L.
      sativus) seeds is proposed as the cause of the neurodegenerative disease
      neurolathyrism, but the mechanism of its action has not been conclusively
      identified. A key factor in excitotoxic neuronal cell death is a disturbance of
      the intracellular Ca2+ homeostasis, including changes in the capacity of
      intracellular Ca2+ stores like the endoplasmic reticulum (ER) or mitochondria. In
      this study, aequorin and other Ca2+ indicators were used in N2a neuroblastoma
      cells to investigate alterations of cellular Ca2+ handling after 24 h exposure to
      L-beta-ODAP. Our data demonstrate increased mitochondrial Ca2+ loading and
      hyperpolarization of the mitochondrial membrane potential (Psi(m)), which was
      specific for L-beta-ODAP and not observed with L-glutamate. We conclude that L
      beta-ODAP disturbs the ER-mitochondrial Ca2+ signaling axis and thereby renders
      the cells more vulnerable to its excitotoxic effects that ultimately will lead to
      cell death.

PMID- 20129667
TI  - Does iron chelation therapy improve survival in regularly transfused lower risk
      MDS patients? A multicenter study by the GFM (Groupe Francophone des
      Myelodysplasies).
AB  - BACKGROUND: Iron chelation therapy (CT) improves survival in thalassemia major
      but its beneficial effects on survival in MDS patients remain uncertain. METHODS:
      We analyzed, by multivariate analysis, survival and causes of deaths in 97 low or
      intermediate 1 IPSS patients regularly transfused as outpatients, chelated or
      not, who were included during a month period and followed for 2.5 years. RESULTS:
      44 (45%) of patients were not chelated and 53 (55%) received CT, mainly with
      deferoxamine, for at least 6 months (median duration of chelation 36 months,
      range 6-131+). During the follow-up period, 66 of the 97 patients died, including
      51% and 73% of chelated and non-chelated patients, respectively. Median overall
      survival was 53 months and 124 months in non-chelated and in chelated patients
      (p<0.0003). Causes of death did not significantly differ between the two groups
      (p=0.51). In multivariate Cox analysis, adequate chelation was the strongest
      independent factor associated with better OS. CONCLUSION: Iron chelation therapy
      appears to improve survival in heavily transfused lower risk MDS, but prospective
      randomized studies are required to confirm our findings, and to determine more
      precisely the mechanisms of this potential survival benefit.

PMID- 20129668
TI  - Immunohistochemical and molecular biomarkers in Coris julis exposed to
      environmental contaminants.
AB  - When a contaminant interacts with biotic components of a marine ecosystem, it
      causes a series of changes that can compromise an entire community (Stebbing,
      1985). This present study wants to focus on changes in the gills of a
      bioindicator benthic organism, Coris julis, collected in Milazzo (Messina,
      Italy), characterized by a strong anthropical impact), compared with individuals
      from the control site (Marinello, Messina). RT-PCR has been used for both MT and
      HSP70, and the respective mRNAs have been visualized by FISH. MT and HSP70
      expression levels increased in individuals collected in Milazzo. The presence of
      numerous apoptotic and proliferating cells and the analysis of several neuronal
      markers by immunohistochemical method give information about the adaptation to a
      heavy metal mixture. The obtained results show that, in stressed fishes,
      defensive processes increase to maintain the normal functions of the organs more
      exposed to the action of polluted substances.

PMID- 20129669
TI  - Investigation of mechanism(s) of DNA damage induced by 4-monochlorobiphenyl
      (PCB3) metabolites.
AB  - 4-Monochlorobiphenyl (PCB3) is readily converted by xenobiotic-metabolizing
      enzymes to dihydroxy-metabolites and quinones. The PCB3 hydroquinone (PCB3-HQ; 2
      (4'-chlorophenyl)-1,4-hydroquinone) induces chromosome loss in Chinese Hamster
      V79 cells, whereas the para-quinone (PCB3-pQ; 2-(4'-chlorophenyl)-1,4
      benzoquinone) very efficiently induces gene mutations and chromosome breaks.
      Apparently, each of these two metabolites, which are a redox pair, has a
      different spectrum of genotoxic effects due to different, metabolite-specific
      mechanisms. We hypothesized that the HQ requires enzymatic activation by
      peroxidases with the formation of reactive oxygen species (ROS) as the ultimate
      genotoxin, whereas the pQ reacts directly with nucleophilic sites in DNA and/or
      proteins. To examine this hypothesis, we employed two cell lines with different
      myeloperoxidase (MPO) activities, MPO-rich HL-60 and MPO-deficient Jurkat cells,
      and measured cytotoxicity, DNA damage (COMET assay), MPO activity, intracellular
      levels of reactive oxygen species (ROS) and intracellular free -SH groups
      (monochlorobimane assay, MCB) and free GSH contents (enzyme recycling method)
      after treatment with PCB3-HQ and PCB3-pQ. We also examined the modulation of
      these effects by normal/low temperature, pre-treatment with an MPO inhibitor
      (succinylacetone, SA), or GSH depletion. PCB3-p-Q increased intracellular ROS
      levels and induced DNA damage in both HL-60 and Jurkat cells at 37 degrees C and
      6 degrees C, indicating a direct, MPO-independent mode of activity. It also
      strongly reduced intracellular free -SH groups and GSH levels in normal and GSH
      depleted cells. Thus the ROS increase could be caused by reduced protection by
      GSH or non-enzymatic autoxidation of the resulting PCB3-HQ-GSH adduct. PCB3-HQ
      did not produce a significant reduction of intracellular GSH in HL-60 cells and
      reduced intracellular free -SH groups only at the highest concentration tested in
      GSH depleted cells. Moreover, PCB3-HQ induced DNA damage and ROS production only
      at 37  degrees C in HL-60 cells, not at 6  degrees C or in Jurkat cells at either
      temperature; no significant DNA damage and ROS production was observed in HL-60
      cells at 37  degrees C if MPO activity was inhibited by SA. These studies show
      that the effects of PCB3-HQ are enzyme dependent, i.e. PCB3-HQ is oxidized by MPO
      in HL-60 cells with the generation of ROS and induction of DNA damage. However,
      this is not the case with the PCB3-pQ, which may produce DNA damage by the
      reactivity of the quinone with the DNA or nuclear proteins, or possibly by
      indirectly increasing intracellular ROS levels by GSH depletion. These different
      modes of action explain not only the different types of genotoxicity observed
      previously, but also suggest different organ specificity of these genotoxins.

PMID- 20129670
TI  - Mutational pressure makes HIV1 gp120 linear B-cell epitopes shorter and may lead
      to their disappearance.
AB  - We showed that nucleotide sequences coding for linear B-cell epitopes of human
      immunodeficiency virus type 1 (HIV1) gp120 protein are enriched with codons
      containing cytosine and guanine in their first and second codon positions.
      Guanine and cytosine are the most mutable nucleotides in HIV1 genes (due to
      APOBEC3 and APOBEC1 editing of viral DNA and RNA, respectively, as well as due to
      reverse transcriptase preference to incorporate 8-oxo-G against C). We introduced
      all the possible G to A, C to U, C to A and G to U single nonsynonymous
      nucleotide mutations in gp120 coding region from the HIV1 reference strain. The
      BepiPred algorithm (www.cbs.dtu.dk/services/BepiPred) was used for the linear B
      cell epitopes predictions. Results of this "in-silico directed mutagenesis"
      showed that: (i) single nonsynonymous G to A transitions will cause partial or
      complete destruction of linear epitopes in 18% of 229 possible cases; (ii) single
      nonsynonymous C to U transitions will cause partial or complete destruction of
      linear epitopes in 58% of 142 possible cases; (iii) single nonsynonymous C to A
      transversions will cause partial or complete destruction of linear epitopes in
      28% of 184 possible cases; (iv) single nonsynonymous G to U transversions will
      cause partial or complete destruction of linear epitopes in 37% of 240 possible
      cases. Moreover, single transition of C to U direction leading to amino acid
      replacement inside an epitope will cause partial or complete destruction of this
      epitope at a probability of 98%.

PMID- 20129671
TI  - Synthesis, characterization and antioxidant activity of water soluble MnIII
      complexes of sulphonato-substituted Schiff base ligands.
AB  - Two new Mn(III) complexes Na[Mn(5-SO(3)-salpnOH)(H(2)O)]5H(2)O (1) and Na[Mn(5
      SO(3)-salpn)(MeOH)]4H(2)O (2) (5-SO(3)-salpnOH=1,3-bis(5
      sulphonatosalicylidenamino)propan-2-ol, 5-SO(3)-salpn=1,3-bis(5
      sulphonatosalicylidenamino)propane) have been prepared and characterized.
      Electrospray ionization-mass spectrometry, UV-visible and (1)H NMR spectroscopic
      studies showed that the two complexes exist in solution as monoanions [Mn(5-SO(3)
      salpn(OH))(solvent)(2)](-), with the ligand bound to Mn(III) through the two
      phenolato-O and two imino-N atoms located in the equatorial plane. The E(1/2) of
      the Mn(III)/Mn(II) couple (-47.11 (1) and -77.80mV (2) vs. Ag/AgCl) allows these
      complexes to efficiently catalyze the dismutation of O(2)(-), with catalytic rate
      constants 2.4x10(6) (1) and 3.6x10(6) (2) M(-1)s(-1), and IC(50) values of 1.14
      (1) and 0.77 (2) muM, obtained through the nitro blue tetrazolium photoreduction
      inhibition superoxide dismutase assay, in aqueous solution of pH 7.8. The two
      complexes are also able to disproportionate up to 250 equivalents of H(2)O(2) in
      aqueous solution of pH 8.0, with initial turnover rates of 178 (1) and 25.2 (2)
      mM H(2)O(2) min(-1)mM(-1)catalyst(-1). Their dual superoxide dismutase/catalase
      activity renders these compounds particularly attractive as catalytic
      antioxidants.

PMID- 20129672
TI  - Transition metal ions and selenite modulate the methylation of arsenite by the
      recombinant human arsenic (+3 oxidation state) methyltransferase (hAS3MT).
AB  - This report demonstrates that transition metal ions and selenite affect the
      arsenite methylation by the recombinant human arsenic (+3 oxidation state)
      methyltransferase (hAS3MT) in vitro. Co(2+), Mn(2+), and Zn(2+) inhibited the
      arsenite methylation by hAS3MT in a concentration-dependent manner and the
      kinetics indicated Co(2+) and Mn(2+) to be mixed (competitive and non
      competitive) inhibitors while Zn(2+) to be a competitive inhibitor. However, only
      a high concentration of Fe(2+) could restrain the methylation. UV-visible, CD and
      fluorescence spectroscopy were used to study the interactions between the metal
      ions above and hAS3MT. Further studies showed that neither superoxide anion nor
      hydrogen peroxide was involved in the transition metal ion or selenite inhibition
      of hAS3MT activity. The inhibition of arsenite methylating activity of hAS3MT by
      selenite was reversed by 2mM DTT (dithiothreitol) but neither by cysteine nor by
      beta-mercaptoethanol. Whereas, besides DTT, cysteine can also prevent the
      inhibition of hAS3MT activity by Co(2+), Mn(2+), and Zn(2+). Free Cys residues
      were involved in the interactions of transition metal ions or selenite with
      hAS3MT. It is proposed that the inhibitory effect of the ions (Co(2+), Mn(2+),
      and Zn(2+)) or selenite on hAS3MT activity might be via the interactions of them
      with free Cys residues in hAS3MT to form inactive protein adducts.

PMID- 20129673
TI  - Reducing the Hypomania Checklist (HCL-32) to a 16-item version.
AB  - BACKGROUND: The under-recognition of hypomanic symptoms by both clinicians and
      patients is a major clinical problem which contributes to misdiagnosis and
      diagnostic delay in patients with bipolar disorder. The recent development of
      validated screening instruments for hypomania, such as the Hypomania Checklist
      (HCL-32), may help to improve the detection of bipolar disorder. In this study,
      we assess whether it is possible to reduce the number of items on the HCL-32
      without any loss in the screening tool's ability to reliably differentiate
      between bipolar disorder (BD) and major depressive disorder (MDD). METHODS: Using
      our large samples of patients with DSM-IV defined bipolar I disorder (BD-I)
      (n=230) and recurrent MDD (n=322), we performed item correlations in order to
      identify potentially redundant items in the HCL-32. We then tested the
      performance of a shortened 16-item HCL questionnaire within a separate sample of
      patients with BD (including BD-I, BD-II and BD-NOS) (n=59) and MDD (n=76).
      RESULTS: The structure of the 16-item HCL demonstrated two main factors similar
      to those identified for the HCL-32 (an 'active-elated' factor and a 'risk
      taking/irritable' factor). A score of 8 or more on a shortened 16-item version of
      the HCL had excellent ability to distinguish between BD and MDD. The sensitivity
      (83%) and specificity (71%) of the 16-item version were very similar to those for
      the full 32-item HCL. LIMITATIONS: The HCL-16 was derived after subjects had
      completed the full HCL-32. It will be important to test the validity of a 'stand
      alone' 16-item HCL questionnaire. CONCLUSIONS: A shortened 16-item HCL (the HCL
      16) is potentially a useful screening tool for hypomania within busy clinical
      settings.

PMID- 20129674
TI  - The influence of affective temperaments and psychopathological traits on the
      definition of bipolar disorder subtypes: a study on bipolar I Italian national
      sample.
AB  - Affective temperament and psychopathological traits such as separation anxiety
      (SA) and interpersonal sensitivity (IPS) are supposed to impact on the clinical
      manifestation and on the course of Bipolar Disorder (BD); in the present study we
      investigated their influence on the definition of BD subtypes. METHOD: : Among
      106 BD-I patients with DSM-IV depressive, manic or mixed episode included in a
      multi-centric Italian study and treated according to the routine clinical
      practice, 89 (84.0%) were in remission after a follow-up period ranging from 3 to
      6 months (Clinical Global Impression-BP [CGI-BP] <2). Remitting patients
      underwent a comprehensive evaluation including self-report questionnaires such as
      the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) scale,
      Separation Anxiety Symptom Inventory (SASI), Interpersonal Sensitivity Measure
      (IPSM) and the Semi-structured interview for Mood Disorder (SIMD-R) administered
      by experienced clinicians. Correlation and factorial analyses were conducted on
      temperamental and psychopathological measures. Comparative analyses were
      conducted on different temperamental subtypes based on the TEMPS-A, SASI and IPSM
      profile. RESULTS: : Depressive, cyclothymic and irritable TEMPS-A score and SASI
      and IPSM total scores were positively and statistically correlated with each
      other. On the contrary, hyperthymic temperament score was negatively correlated
      with depressive temperament and not significantly correlated with the other
      temperamental and psychopathological dimensions. The factorial analysis of the
      TEMPS-A subscales and SASI and IPSM total scores allowed the extraction of 2
      factors: the cyclothymic-sensitive (explaining 46% of the variance) that
      included, as positive components, depressive, cyclothymic, irritable temperaments
      and SASI and IPSM scores; the hyperthymic (explaining the 19% of the variance)
      included hyperthymic temperament as the only positive component and depressive
      temperament and IPSM, as negative components. Dominant cyclothymic-sensitive
      patients (n=49) were more frequently females and reported higher number of
      depressive, hypomanic and suicide attempts when compared to the dominant
      hyperthymic patients (n=40). On the contrary, these latter showed a higher number
      of manic episodes and hospitalizations than cyclothymic-sensitive patients. The
      rates of first-degree family history for both mood and anxiety disorders were
      higher in cyclothymic-sensitive than in hyperthymic patients. Cyclothymic
      sensitive patients also reported more axis I lifetime co-morbidities with Panic
      Disorder/Agoraphobia and Social Anxiety Disorder in comparison with hyperthymics.
      As concerns axis II co-morbidity the cyclothymic-sensitive patients met more
      frequently DSM-IV criteria 1, 5 and 7 for borderline personality disorder than
      the hyperthymics. On the contrary, antisocial personality disorder was more
      represented among hyperthymic than cyclothymic patients, in particular for DSM-IV
      criteria 1 and 6. LIMITATION: : No blind evaluation and uncertain validity of
      personality inventory. CONCLUSION: : Our results support the view that affective
      temperaments influence the clinical features of BD in terms of both clinical and
      course characteristics, family history and axis I and II co-morbidities.
      Hypothetical temperamental subtypes as measured by TEMPS-A presented important
      interrelationships that permit to reliably isolate two fundamental temperamental
      disposition: the first characterized by rapid fluctuations of mood and emotional
      instability, and the second by hyperactivity, high level of energy and emotional
      intensity. Dominant cyclothymic and hyperthymic bipolar I patients reported
      important differences in terms of gender distribution, number and polarity of
      previous episodes, hospitalizations, suicidality, rates of co-morbid anxiety and
      personality traits and disorders. Our data are consistent with the hypothesis
      that affective temperaments, and in particular cyclothymia, could be utilized as
      quantitative, intermediate phenotypes in order to identify BD susceptibility
      genes.

PMID- 20129675
TI  - Benzodiazepine and cyclopyrrolone reduction in general practice--does this lead
      to change in the use of antidepressants? A study based on a Danish population.
AB  - BACKGROUND: The consumption of benzodiazepines and cyclopyrrolones has in recent
      years attracted considerable interest due to serious side effects. In twelve
      health care practices in Denmark a few simple rules to reduce the consumption
      were established. Telephone recipes were abolished, and prescriptions were issued
      for only a single month's usage and only following personal consultation. These
      rules are generally in accordance with recommendations applicable in, for
      example, England, Norway and Denmark. After 15 months, consumption was roughly
      halved. There is a general lack of knowledge about whether an intervention as
      described above leads to a substitution with other medicines. Here, especially
      antidepressants are in the spotlight. METHODS: In the twelve health care
      practices, the consumption of antidepressants before, during and after the
      intervention was followed. RESULTS: The total consumption of antidepressants rose
      by 5.2% per year during the 18 month observation period. This should be compared
      to the fact that the county had an increase of 8.6% per year during the same
      period. This increase occurred mainly in the group of selective serotonin
      reuptake inhibitors. LIMITATIONS: The study does not provide information about
      prescription changes for individual users, or for changes in the number of users.
      The study is limited to the total prescribed volume of antidepressants.
      CONCLUSION: The average prescription volume for the twelve health care practices
      corresponds to a relative decline. Fears that an intervention of the type
      mentioned above would lead to an uncontrollable increase in the consumption of
      antidepressants are unfounded.

PMID- 20129676
TI  - Assessing mixed anxiety-depressive disorder. A national primary care survey.
AB  - Prevalence and risk factors associated with mixed anxiety-depressive disorder
      (MAD) have yet to be established. Using MINI 5.0.1 and HADS, a two-week survey
      involving 21,644 primary care patients was carried out. We found 1.8% of subjects
      with MAD and 20% of subjects with a co-morbid anxiety and depression (CAD)
      disorder. MAD patients without a past history of anxiety/affective episodes were
      defined as "pure MAD" (pMAD: 0.9% of the sample). While MAD patients showed a
      number of differences vs. the other groups of patients in the socio-demographic
      statistics, pMAD patients were not different, apart from a higher proportion of
      males vs. CAD patients. Nearly in all the comparisons, MAD and pMAD patients
      showed lower association with life events and with a familial predisposition than
      the other patients. On HADS assessment, MAD showed a higher risk of anxiety and
      depressive symptoms than anxiety diagnoses, a lower risk of depressive symptoms
      than depressive diagnoses and a lower risk of both anxiety and depressive
      symptoms than CAD. Since more than a half of MAD patients were classified as
      pMAD, the hypothesis that MAD should be viewed as a partial remission of a major
      depression is not entirely confirmed in our study.

PMID- 20129677
TI  - Glial cell line-derived neurotrophic factor is increased in cerebrospinal fluid
      but decreased in blood during long-term pain.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is involved in inflammation
      and pain, roles which remain to be delineated clinically. We aimed to evaluate
      the role of central nervous and peripheral GDNF in long-term pain patients and in
      controls by analysing intrathecal and blood concentrations of GDNF. Simultaneous
      measurements of pro-inflammatory cytokines IL-1beta, TNF-alpha and IL-6, anti
      inflammatory cytokine IL-10 and chemokine IL-8 served to define inflammatory
      responses. Generally, blood levels of GDNF were higher than corresponding
      intrathecal levels. Pain was associated with levels of GDNF that were increased
      intrathecally, but decreased in blood. IL-8 was uniformly higher in pain
      patients.

PMID- 20129678
TI  - Bupivacaine versus normal saline for relief of post-adenotonsillectomy pain in
      children: a meta-analysis.
AB  - OBJECTIVE: A meta-analysis was performed to explore the role of peri-operative
      bupivacaine infiltration in the relief of pain in adenotonsillectomy. METHODS:
      Data from Medline, EMBase, Springer and the Cochrane Collaboration database were
      searched. Reference lists from identified publications were scanned. RevMan 5.0
      software was used for statistical analysis. RESULTS: 7 random controlled tests (a
      total of 286 cases) were included. Pain intensity was evaluated by VAS score or
      Cheops score. The pain of group bupivacaine (Group B) was less severe than group
      placebo (Group P). Analgesic requirement of Group B was less than Group P.
      Nevertheless the difference of complication between bupivacaine and placebo had
      no statistical difference. CONCLUSION: Bupivacaine infiltration is a safe and
      effective method for relief of pediatric post-adenotonsillectomy pain.

PMID- 20129680
TI  - Effects of exposure to smoking on the microbial flora of children and their
      parents.
AB  - This review presents our studies that investigated the effects of exposure to
      direct and indirect smoking on the colonization with pathogenic bacteria and
      organisms that interfere with their growth. The flora of smokers (S) contained
      less aerobic and anaerobic organisms with interfering capability and more
      potential pathogens as compared with non-smokers (N-S). The high number of
      pathogens and the low number of interfering organisms found in the nasopharynx of
      smokers revert to normal levels after complete cessation of smoking. A high
      recovery rate of potential pathogens and low number of interfering organisms were
      observed in otitis media prone (OMP) children. This was not related to their
      parents smoking habits. The flora of S parents contains more potential pathogens
      that are similar to the one recovered from their OMP children, and less
      interfering organisms as compared to N-S parents. Parents that smoked were more
      often colonized by potential pathogens than parents that did not smoke. The flora
      of healthy children of S parents contained high number of potential pathogens
      similar to the one found in their parents and OMP children. Concordance with
      pathogens in the parent was high among the OMP children of S parents but this was
      not observed in OMP children of N-S. A higher recovery rate of potential
      pathogenic organisms was observed in OMP children of both S and N-S parents, as
      compared to healthy children whose parents were N-S. Since S parents harbor more
      potential pathogens and less interfering organisms they may serve as a source of
      pathogens that can colonize and/or infect their children. These studies
      illustrate the adverse effects of direct and indirect exposure to smoking on
      colonization with potential pathogens.

PMID- 20129679
TI  - The effects of topical viscous lignocaine 2% versus per-rectal diclofenac in
      early post-tonsillectomy pain in children.
AB  - INTRODUCTION: Tonsillectomy is frequently associated with postoperative pain of
      considerable duration, which is usually accompanied by the substantial
      consumption of both opioid and non-opioid analgesic such as NSAIDs and local
      anaesthetics. OBJECTIVE: The aim of this study was to evaluate the efficacy
      between 2% viscous lignocaine and sodium diclofenac based upon the visual
      analogue scores (VASs), consumption of pethidine 0.5mgkg(-1) as the rescue drug
      postoperatively and time taken to resume feeding. METHODS: 130 patients aged
      between 5 and 12 years old were randomly allocated into 2 groups to be given
      either 2% viscous lignocaine 4mgkg(-1) body weight topically post-tonsillectomy
      or sodium diclofenac 1mgkg(-1) per-rectal post-induction of anaesthesia.
      Postoperatively visual analogues score was done for 24h, the amount of pethidine
      given and time when the patient start taking oral feeding of clear fluid, soft
      diet and normal diet were documented. RESULTS: There was no significant
      difference in the visual analogue scores in both groups, however the requirement
      of pethidine as the rescue drug postoperatively was significant 2h post
      tonsillectomy (p=0.023) in viscous lignocaine group compared to sodium
      diclofenac. The time taken to resume oral feeding and soft diet was also
      significant in viscous lignocaine group (p=0.016 and p=0.007) whereas there was
      no significant in taking normal diet. CONCLUSION: We concluded that 2% viscous
      lignocaine applied topically post-tonsillectomy is comparable to sodium
      diclofenac per-rectal in providing analgesia and faster oral feeding.

PMID- 20129681
TI  - Effects of pulp and paper mill effluent extractives on aromatase CYP19a gene
      expression and sex steroid levels in juvenile triploid rainbow trout.
AB  - We evaluated plasma testosterone (T) and 17beta-estradiol (E2) levels and ovarian
      aromatase CYP19a gene expression following a single intraperitoneal injection of
      Chilean pulp and paper mill effluent extracts into juvenile triploid rainbow
      trout. Fish injected with untreated effluent extracts had increased plasma T
      after 4 days, while plasma E2 concentration was increased in fish injected with
      both primary and secondary treated effluent extracts at the same sampling period.
      Ovarian CYP19a gene expression as measured by qRT-PCR was significantly induced
      in fish injected with the untreated, primary and secondary treated pulp and paper
      mill effluent extracts. Similar induction of CYP19a expression was found in fish
      injected with the androgens androstenedione (ADD) and T. A Principal Component
      Analysis (PCA) was conducted in order to identify structure in relationships
      between all measured variables and identifying which factors were most
      responsible for the variance observed within the plasma steroid levels,
      upregulation of ovarian CYP19a gene expression and the final estrogenic effect of
      increased plasma VTG levels. This analysis indicated a cluster correlation
      between plasma T levels and CYP19a gene expression (Factor 1, explaining 27.2% of
      total variance), a cluster including condition factor and liver somatic index
      (Factor 2, explaining 17.3%) and an additional cluster including plasma E2 and
      vitellogenin levels (Factor 3, explaining an additional 15.8%). The present
      results indicate that Chilean pulp and paper mill effluent extracts cause
      estrogenic effects in triploid rainbow trout. These effects could be related to
      the compounds present in the effluent that act as estrogen receptor agonists, or
      that induce changes leading to increased amounts of endogenous estrogens,
      reflected by increased E2 levels and induced aromatase expression/activity.

PMID- 20129682
TI  - Incorporating farmer observations in efforts to manage bovine tuberculosis using
      barrier fencing at the wildlife-livestock interface.
AB  - A federal and provincial cost-shared program was initiated in 2001 around Riding
      Mountain National Park in southwestern Manitoba, Canada to provide free game wire
      barrier fences for baled hay storage areas to prevent transmission of TB among
      cattle (Bos taurus), wild elk (Cervus elaphus), and deer (Odocoileus
      virginianus). Farmer observations of cervids on their farms were evaluated by
      interviewing 50 farmers that owned a game wire fence for >1 year. Of those
      interviewed, 82% reported some type of elk or deer damage to hay bales in the
      field or in their yard prior to fencing. After fencing, 23% of respondents
      reported some annual damage to stored hay bales that were not inside the fence,
      but there was a 100% decrease in the estimated annual value of hay losses.
      Incursions of deer inside the barrier fence were reported by 18% of respondents
      and most of these were due to leaving gates open. No incursions of elk inside a
      barrier fence were reported. Despite the important successes achieved, barrier
      fencing of hay bales alone does not completely protect cattle from bovine
      tuberculosis.

PMID- 20129683
TI  - A Bayesian Weibull survival model for time to infection data measured with delay.
AB  - Survival analysis methods can be used to identify factors associated with the
      time to induction of infection. In the absence of a perfect test, detection of
      infection is generally delayed and depends on the duration of the latent
      infection period. We assess, via simulations, the impact of ignoring the delayed
      detection of infection on estimated survival times and propose a Bayesian Weibull
      regression model, which adjusts for the delayed detection of infection. The
      presence of non-differential detection delay seriously biased the baseline hazard
      and the shape of the hazard function. For differential detection delay, the
      associated regression coefficients were also biased. The extent of bias largely
      depended on the longevity of the delay. In all considered simulation scenarios
      our model led to corrected estimates. We utilized the proposed model in order to
      assess the age at natural infection with Mycobacterium avium subsp.
      paratuberculosis (MAP) in Danish dairy cattle from the analysis of available time
      to milk-seropositivity data that detected infection with delay. The proposed
      model captured the inverse relationship between the incidence rate of infection
      and that of seroconversion with time: susceptibility to infection decreases with
      time (shape parameter under the proposed model was rho=0.56<1), while older
      animals had a higher probability of sero-converting (rho=2.67>1, under standard
      Weibull regression). Cows infected earlier in their lives were more likely to
      subsequently shed detectable levels of MAP and, hence, be a liability to herd
      mates. Our approach can be particularly useful in the case of chronic infections
      with a long latent infection period, which, if ignored, severely affects survival
      estimates.

PMID- 20129684
TI  - Disease surveillance and referral bias in the veterinary medical database.
AB  - The Veterinary Medical Database (VMDB) is a summary of veterinary medical records
      from North American veterinary schools, and is a potential source of disease
      surveillance information for companion animals. A retrospective record search
      from four U.S. university veterinary teaching hospitals was used to calculate
      crude disease rates. Our objectives were to evaluate the utility of the database
      for disease surveillance purposes by comparing the utility of two methodologies
      for creating disease categories, and to evaluate the database for evidence of
      referral bias. Summaries of the medical records from November 2006 to October
      2007 for 9577 dogs and 4445 cats were retrieved from VMDB for all canines and
      felines treated at Kansas State University, Colorado State University, Purdue
      University and Ohio State University. Disease frequency, computed as apparent
      period-prevalence and as the percentage of veterinary visits, was compiled for 30
      disease categories that were formulated by one of two methods. To assess the
      possible impact of referral bias, disease rates were compared between animals
      residing in zip codes within 5 miles of the hospitals (zone 1) and those animals
      living at more distant locations (zone 2). When compared to zone 1 animals,
      disease conditions commonly associated with primary veterinary care were reduced
      by 29-76% within zone 2, and selected diseases generally associated with more
      specialized care were increased from 46 to 80% among zone 2 animals. The major
      differences in disease prevalence seen between zones suggests that substantial
      referral bias may exist, and that adjustment on the basis of geographical
      proximity to the university teaching hospitals may be useful in reducing this
      type of selection bias in the VMDB, thereby improve the accuracy of prevalence
      estimates and enhancing the utility of this database for purposes of disease
      surveillance.

PMID- 20129685
TI  - Ecological risk assessment for transgenic crops: separating the seed from the
      chaff.

PMID- 20129686
TI  - Detection of Listeria monocytogenes in raw and pasteurized liquid whole eggs and
      characterization by PFGE.
AB  - Listeria monocytogenes has been recognized as a human pathogen for decades and is
      known to be an important foodborne pathogen. There have been no documented
      foodborne L. monocytogenes illnesses due to the consumption of eggs or egg
      products, even though the bacterium has been isolated from faeces, body fluid,
      and oviducts of asymptomatic laying hens. In order to describe L. monocytogenes
      contamination of egg products, 144 liquid whole egg samples were collected from 3
      different egg-breaking plants during 3 sampling periods. L. monocytogenes
      detection was performed on raw samples stored at 2 degrees C for two days (D+2)
      and on pasteurized samples stored at 2 degrees C at D+2 and at shelf-life date
      (SLD). L. monocytogenes was detected in 25 of the 144 raw egg samples collected,
      in 4 of the 144 pasteurized egg samples at D+2 and in 2 of the 144 ones analysed
      at SLD. Contamination of raw egg products appeared to be season dependant and was
      higher during summer and winter than during autumn. One hundred and ninety-six L.
      monocytogenes isolates were collected and serotyped; 3 serovars were
      demonstrated. The dominant serovar was L. monocytogenes 1/2a which was presented
      by 94.4% of the isolates. Typing of 196 L. monocytogenes isolates was carried out
      by macrorestriction of the genomic DNA with ApaI and AscI enzymes followed by
      pulsed field gel electrophoresis (PFGE). A large diversity was observed with 21
      genotypes of L. monocytogenes, even for a given manufacturer. Nevertheless, most
      of the egg product samples were contaminated by one genotype, except for five
      samples which were contaminated by two or three distinct genotypes. The genotypes
      seem to be specific to each manufacturer. No cluster of L. monocytogenes was
      found to recur in the different plants over successive seasons.

PMID- 20129687
TI  - Changes of serum omentin-1 levels in normal subjects and in patients with
      impaired glucose regulation and with newly diagnosed and untreated type 2
      diabetes.
AB  - AIMS: To assay the levels of serum omentin-1 in subjects with different levels of
      glucose regulation and to analyze the relationship between serum omentin-1 levels
      and body mass index (BMI), glycoslated hemoglobin (HbA1c), plasma glucose,
      insulin resistance index (HOMA-IR), TNF-alpha and IL-6 levels. METHODS: Forty-six
      patients with impaired glucose regulation (IGR), 55 patients with newly diagnosed
      and untreated type 2 diabetes mellitus (T2DM), and 50 subjects with normal
      glucose tolerance (NGT) were enrolled in this study. The levels of serum omentin
      1 and plasma glucose at fasting and at 2h after glucose load and fasting serum
      levels of TNF-alpha, IL-6, insulin, and HbA1c were measured. HOMA-IR was
      calculated. RESULTS: The levels of serum omentin-1 were lower in the IGR and T2DM
      groups than in the NGT group. Within groups, omentin-1 levels were no significant
      difference before and after glucose load. The level of serum omentin-1 was
      negatively correlated to BMI, HOMA-IR, fasting insulin, TNF-alpha, IL-6, plasma
      glucose. HOMA-IR and BMI were independent related factors that influenced the
      levels of serum omentin-1. CONCLUSIONS: Serum omentin-1 levels were decreased in
      impaired glucose regulation subjects. Lack of omentin-1 may contribute to the
      development of insulin resistance and T2DM.

PMID- 20129688
TI  - Microvascular complications are associated with low levels of maternal sE
      selectin and sVCAM-1 in pregnancy complicated with pregestational diabetes
      mellitus.
AB  - Pregestational diabetes with vasculopathy in pregnant women is still associated
      with increased risk for severe maternal and foetal complications and their
      pathomechanism remains unclear. We investigate endothelial function in diabetic
      pregnant women with and without vascular disease, measured as changes in
      concentrations of soluble E-selectin and VCAM-1 throughout pregnancy. 121
      pregnant women with PGDM and singleton pregnancy (30 participants with
      vasculopathy, 91 without vasculopathy) were enrolled into the prospective study.
      Control group consisted of 20 nondiabetic pregnant women in uncomplicated
      gestation, sampled cross-sectionally in early pregnancy and at term. We
      demonstrated lower concentrations of circulating sE-selectin both in early and in
      late diabetic gestation, irrespective of a concomitant vasculopathy. We also
      found reduced concentrations of sVCAM-1 in late gestation in diabetic pregnancies
      both with and without vascular disease, and reduced increase in its levels with
      gestation. We report significantly elevated concentrations of sVCAM-1 in early
      pregnancy in diabetic participants with retinopathy and nephropathy comparing
      with patients with retinopathy only and nondiabetic pregnant controls. We noted a
      general pattern of pregestational diabetes associated with reduced levels of cell
      adhesion molecules in early pregnancy with a further reduction during gestation,
      except for participants with combined retino- and nephropathy.

PMID- 20129689
TI  - Reactivation of hepatitis B virus after transarterial chemo-embolization for
      hepatocellular carcinoma in one patient with negative hepatitis B surface
      antigen.

PMID- 20129690
TI  - Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis
      C infected patients and limit the extent of fibrosis.
AB  - BACKGROUND & AIMS: Weak hepatitis C virus (HCV) specific immunity in peripheral
      blood has been shown to be partially controlled by regulatory T cells (Treg).
      However, little is known about Treg present in livers of HCV-infected patients,
      their association with clinical parameters, and immunopathology resulting in
      disease progression. METHODS: The frequency and phenotype of CD4+FoxP3+ Treg,
      conventional CD4+ T cells, and the distribution of lymphocytes and leukocytes
      were studied by multi-color flowcytometry in liver and peripheral blood of 43
      chronic HCV patients at different phases of liver disease. Comparisons between
      healthy blood and liver and correlations with disease parameters were made.
      RESULTS: An extensive lymphocyte infiltration containing abundant numbers of
      CD4+FoxP3+ Treg was present in HCV-infected livers, while absent from healthy
      liver. Moreover, in all patients, intrahepatic CD4+FoxP3+ Treg showed a fully
      differentiated and highly activated phenotype on the basis of the surface markers
      CD45RO, CCR7, CTLA-4 and HLA-DR. These Treg were more numerous in those HCV
      infected livers showing only limited fibrosis. However, HCV RNA loads or alanine
      transaminase levels did not correlate with CD4+FoxP3+ Treg frequencies.
      CONCLUSIONS: Our data demonstrate that large numbers of highly activated and
      differentiated CD4+FoxP3+ Treg localize to the infiltrated chronic HCV-infected
      liver and may result in limiting the extent of fibrosis. This suggests that
      CD4+FoxP3+ Treg play a pivotal role in limiting collateral damage by suppressing
      excessive HCV-induced immune activation.

PMID- 20129691
TI  - International hepatology.

PMID- 20129692
TI  - TGF-beta enhances alcohol dependent hepatocyte damage via down-regulation of
      alcohol dehydrogenase I.
AB  - BACKGROUND & AIMS: Adverse alcohol effects in the liver involve oxidative
      metabolism, fat deposition and release of fibrogenic mediators, including TGF
      beta. The work presents an assessment of liver damaging cross-talk between
      ethanol and TGF-beta in hepatocytes. METHODS: To investigate TGF-beta effects on
      hepatocytes, microarray analyses were performed and validated by qRT-PCR, Western
      blot analysis and immunohistochemistry. The cellular state was determined by
      assessing lactate dehydrogenase, cellular glutathione, reactive oxygen species,
      lipid peroxidation and neutral lipid deposition. RNA interference was used for
      gene silencing in vitro. RESULTS: TGF-beta is induced in mouse livers after
      chronic ethanol insult, enhances ethanol induced oxidative stress and toxicity
      towards cultured hepatocytes plus induces lipid-, oxidative stress metabolism-
      and fibrogenesis-gene expression signatures. Interestingly, TGF-beta down
      regulates alcohol metabolizing enzyme Adh1 mRNA in cultured hepatocytes and liver
      tissue from TGF-beta transgenic mice via the ALK5/Smad2/3 signalling branch, with
      Smad7 as a potent negative regulator. ADH1 deficiency is a determining factor for
      the increased lipid accumulation and Cyp2E1 dependent toxicity in liver cells
      upon alcohol challenge. Further, ADH1 expression was decreased during liver
      damage in an intragastric ethanol infusion mouse model. CONCLUSION: In the
      presence of ethanol, TGF-beta displays pro-steatotic action in hepatocytes via
      decreasing ADH1 expression. Low ADH1 levels are correlated with enhanced
      hepatocyte damage upon chronic alcohol consumption by favoring secondary
      metabolic pathways.

PMID- 20129693
TI  - New tricks with old genes: the genetic bases of novel cnidarian traits.
AB  - Recent thought on genome evolution has focused on the creation of new genes and
      changes in regulatory mechanisms while ignoring the role of selective gene loss
      in shaping genomes. Using data from two cnidarians, the jellyfish Clytia and the
      coral Acropora, we examined the relative significance of new 'taxonomically
      restricted' genes and selectively retained ancestral genes in enabling the
      evolution of novel traits. Consistent with its more complex life-cycle, the
      proportion of novel genes identified in Clytia was higher than that in the 'polyp
      only' cnidarians Nematostella and Hydra, but each of these cnidarians has
      retained a proportion of ancestral genes not present in the other two. The
      ubiquity and near-stochastic nature of gene loss can explain the discord between
      patterns of gene distribution and taxonomy.

PMID- 20129694
TI  - The trajectory of lung cancer patients in Western Australia--a data linkage
      study: still a grim tale.
AB  - OBJECTIVE: To plot the trajectory of lung cancer patients by linking multiple
      data sources in Western Australia. DESIGN: Database survey, data linkage and
      postal survey. SETTING: Western Australia. PARTICIPANTS: Lung cancer patients
      registered on the cancer registry database of Western Australia, April 2006 to
      March 2007. MAIN OUTCOME MEASURES: Morbidity, mortality, and medical procedures.
      RESULTS: 950 lung cancer patients were registered on the cancer registry database
      from April 2006 to March 2007. Sixty five percent were male with a mean age at
      diagnosis of 70 years (SD 11 years). Approximately 30% were from regional and
      remote areas of Western Australia. 76% reported a history of smoking, with a mean
      of 41 pack-years per smoker. One in four cases had metastases at diagnosis. 18%
      of cases from a tertiary hospital received no active treatment. The median time
      from the first visit to GP with recognized cancer symptoms until consultation
      with a specialist was 2 weeks. One in five cases presented directly to the
      hospital Emergency Department. For 16% of all cases, no symptoms were recorded in
      the hospital administrative records at the time of presentation. Fifty-two
      percent of patients had chemotherapy, 49% received radiotherapy and 21% had
      surgery. 13% of treated patients were readmitted to hospital with complications
      of therapy. Median survival was 33 weeks (95% CI 30-40). CONCLUSION: Data linkage
      offers limited prospects for exploring the trajectory of patients with lung
      cancer in Western Australia. The available data indicate that the prognosis of
      lung cancer remains very poor and that a high proportion of patients are still
      diagnosed with advanced disease. There is no evidence to suggest that a greater
      proportion of patients are being offered surgical treatment compared to more than
      a decade ago. However a greater proportion of cases now receive adjuvant
      therapies and overall median survival has improved by a matter of weeks.

PMID- 20129695
TI  - The area composita of adhering junctions connecting heart muscle cells of
      vertebrates. VII. The different types of lateral junctions between the special
      cardiomyocytes of the conduction system of ovine and bovine hearts.
AB  - Postnatal development of mammalian cardiomyocytes in the working myocardium is
      characterized by a near-complete translocation of both kinds of adhering
      junctions (AJs), i.e. desmosomes and fasciae adhaerentes (FAs), to the polar
      intercalated disk (ID) regions where they cluster, fuse and molecularly
      amalgamate to extended hybrid intercellular junction structures, the area
      composita (composite junction; AC). Using immunofluorescence and immunoelectron
      microscopy we now report that the AJ structures of the conduction system, in
      particular those of the Purkinje fiber cells of cows and sheep are fundamentally
      different. Here the numerous AJs remain in lateral connections with other
      conductive cells. Desmosomal or desmosome-like junctions can still be
      distinguished from FA junctions, and a third type of AJs can be identified which
      shows colocalization of desmosomal and FA proteins, i.e. an AC character. These
      results, together with demonstrations of other cell type cytoskeletal markers
      such as alpha-cardiac actin and desmin, support the concept that conductive cells
      are derived from embryonal cardiomyocytes and are arrested at an early stage of
      differentiation. We also show that the conductive cells have extended plasma
      membrane regions characterized by an exceptionally high proportion of junctions
      with desmosomal character and proteins, amounting to 50% and more, resulting in
      the highest desmosome protein packing so far described in non-epithelial cells.
      The relevance of these junctions for the formation, maintenance and functions of
      the conductive system is discussed, together with the conclusion that the
      desmosome-rich regions of conductive cells are among the most vulnerable sites
      for functional disorders caused by desmosomal protein mutations.

PMID- 20129697
TI  - Microtubule-dependent localization of profilin I mRNA to actin polymerization
      sites in serum-stimulated cells.
AB  - Specific localization of messenger RNA (mRNA) appears to be a general mechanism
      to accumulate certain proteins to subcellular compartments for participation in
      local processes, thereby maintaining cell polarity under strict spatiotemporal
      control. Transportation of mRNA with associated protein components (RNP granules)
      by the actin microfilament or the microtubule systems is one important mechanism
      to achieve this locally distributed protein production. Here we provide evidence
      for a microtubule-dependent localization of mRNA encoding the actin regulatory
      protein profilin to sites in mouse embryonic fibroblasts, which express enhanced
      actin polymerization.

PMID- 20129696
TI  - BMP-2 and TGF-beta1 differentially control expression of type II procollagen and
      alpha 10 and alpha 11 integrins in mouse chondrocytes.
AB  - Bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta1 are
      multifunctional cytokines both proposed as stimulants for cartilage repair. Thus
      it is crucial to closely examine and compare their effects on the expression of
      key markers of the chondrocyte phenotype, at the gene and protein level. In this
      study, the expression of alpha 10 and alpha 11 integrin subunits and the IIA/IIB
      spliced forms of type II procollagen have been monitored for the first time in
      parallel in the same in vitro model of mouse chondrocyte
      dedifferentiation/redifferentiation. We demonstrated that TGF-beta1 stimulates
      the expression of the non-chondrogenic form of type II procollagen, IIA isoform,
      and of a marker of mesenchymal tissues, i.e. the alpha 11 integrin subunit. On
      the contrary, BMP-2 stimulates the cartilage-specific form of type II
      procollagen, IIB isoform, and a specific marker of chondrocytes, i.e. the alpha
      10 integrin subunit. Collectively, our results demonstrate that BMP-2 has a
      better capability than TGF-beta1 to stimulate chondrocyte redifferentiation and
      reveal that the relative expressions of type IIB to type IIA procollagens and
      alpha 10 to alpha 11 integrin subunits are good markers to define the
      differentiation state of chondrocytes. In addition, adenoviral expression of
      Smad6, an inhibitor of BMP canonical Smad signaling, did not affect expression of
      total type II procollagen or the ratio of type IIA and type IIB isoforms in mouse
      chondrocytes exposed to BMP-2. This result strongly suggests that signaling
      pathways other than Smad proteins are involved in the effect of BMP-2 on type II
      procollagen expression.

PMID- 20129698
TI  - Ponsin interacts with Nck adapter proteins: implications for a role in
      cytoskeletal remodelling during differentiation of skeletal muscle cells.
AB  - Skeletal muscle differentiation is a complex process: It is characterised by
      changes in gene expression and protein composition. Simultaneously, a dramatic
      remodelling of the cytoskeleton and associated cell-matrix contacts, the
      costameres, occurs. The expression and localisation of the protein ponsin at cell
      matrix contacts marks the establishment of costameres. In this report we show
      that skeletal muscle cells are characterised by a novel ponsin isoform, which
      contains a large insertion in its carboxy-terminus. This skeletal muscle-specific
      module binds the adapter proteins Nck1 and Nck2, and increased co-localisation of
      ponsin with Nck2 is observed at remodelling cell-matrix contacts of
      differentiating skeletal muscle cells. Since this ponsin insertion can be
      phosphorylated, it may adjust the interaction affinity with Nck adapter proteins.
      The novel ponsin isoform and its interaction with Nck1/2 provide exciting insight
      into the convergence of signalling pathways at the costameres, and its crucial
      role for skeletal muscle differentiation and re-generation.

PMID- 20129699
TI  - Gabaculine alters plastid development and differentially affects abundance of
      plastid-encoded DPOR and nuclear-encoded GluTR and FLU-like proteins in spruce
      cotyledons.
AB  - Synthesis of 5-aminolevulinic acid (ALA) represents a rate limiting step in the
      tetrapyrrole biosynthetic pathway, and is regulated by metabolic feedback control
      of glutamyl-tRNA reductase (GluTR) activity. The FLU protein has been attributed
      to this regulation. Later in the biosynthetic pathway, reduction of
      protochlorophyllide (Pchlide), catalyzed by protochlorophyllide oxidoreductase
      (POR), ensures another important regulatory step in the chlorophyll biosynthesis.
      In the present work, we investigated the expression and cellular abundance of
      nuclear-encoded and plastid-encoded proteins involved in ALA synthesis and
      Pchlide reduction in Norway spruce (Picea abies L. Karst.) as a representative of
      plant species with high ability to synthesize chlorophyll in the dark. Using dark
      grown, light/dark-grown and gabaculine-treated seedlings, we demonstrated that
      gabaculine-impaired etiochloroplast and chloroplast development has no negative
      effect on GluTR accumulation in the cotyledons. However, in contrast to control
      plants, the relative amount of GluTR was similar both in the dark-grown and
      light/dark-grown gabaculine-treated seedlings. We identified a partial sequence
      of the FLU-like gene in Norway spruce, and using antibodies against the FLU-like
      protein (FLP), we showed that FLP accumulated mostly in the dark-grown control
      seedlings and gabaculine-treated seedlings. In contrast to nuclear-encoded GluTR
      and FLP, accumulation of plastid-encoded light-independent POR (DPOR) was
      sensitive to gabaculine treatment. The levels of DPOR subunits were substantially
      lower in the light/dark-grown control seedlings and gabaculine-treated seedlings,
      although the corresponding genes chlL, chlN and chlB were expressed. Since we
      analyzed the samples with different plastid types, plastid ultrastructure and
      physiological parameters like Pchlide and chlorophyll contents, in vivo
      chlorophyll fluorescence and photosynthetic efficiency of the seedlings were
      characterized. Apart from etiochloroplast-specific accumulation of the DPOR
      subunits, we described, in some detail, additional specific features of
      chlorophyll biosynthesis in the spruce seedlings that differ from those known in
      angiosperms.

PMID- 20129700
TI  - Expression of sweet potato cysteine protease SPCP2 altered developmental
      characteristics and stress responses in transgenic Arabidopsis plants.
AB  - In this report a full-length cDNA, SPCP2, which encoded a putative papain-like
      cysteine protease was isolated from senescent leaves of sweet potato (Ipomoea
      batatas). SPCP2 contained 1101 nucleotides (366 amino acids) in its open reading
      frame, and exhibited high amino acid sequence identities (ca. 68% to 83%) with
      plant cysteine proteases, including Actinidia deliciosa, Arabidopsis thaliana,
      Brassica oleracea, Phaseolus vulgaris, Pisum sativa, Vicia faba, Vicia sativa and
      Vigna mungo. RT-PCR analysis showed that SPCP2 gene expression was enhanced
      significantly in natural senescent leaves and in dark-, abscisic acid- (ABA-),
      jasmonic acid- (JA-) and ethephon-induced senescent leaves, but was almost not
      detected in mature green leaves, stems, and roots. Transgenic Arabidopsis with
      constitutive SPCP2 expression exhibited earlier floral transition from vegetative
      to reproductive growth, higher percentage of incompletely developed siliques per
      plant, reduced average fresh weight and lower germination percentage of seed, and
      higher salt and drought stress tolerance compared to those of control. Based on
      these results we conclude that sweet potato papain-like cysteine protease, SPCP2,
      is a functional senescence-associated gene, and its expression causes altered
      developmental characteristics and stress responses in transgenic Arabidopsis
      plants.

PMID- 20129701
TI  - A 1-m distance is not safe for children with cystic fibrosis at risk for cross
      infection with Pseudomonas aeruginosa.
AB  - Although maintaining a distance of 1 m between persons with cystic fibrosis (CF)
      is a universal recommendation to prevent respiratory cross-infections such as
      Pseudomonas aeruginosa, evidence supporting this preventive measure is scarce.
      Examining 336 samples from 42 patients with CF collected experimentally from
      sterile surfaces after speaking and coughing, we found that transmission of P
      aeruginosa beyond 1 m is possible during both talking and coughing, although the
      probability is low (1.7%).

PMID- 20129702
TI  - The impact of portable high-efficiency particulate air filters on the incidence
      of invasive aspergillosis in a large acute tertiary-care hospital.
AB  - BACKGROUND: Worldwide, the frequency of invasive fungal infections has been
      increasing, with a corresponding increase in the numbers of high-risk patients.
      Exposure reduction through the use of high-efficiency particulate air (HEPA)
      filters has been the preferred primary preventive strategy for these high-risk
      patients. Although the efficiency and benefits of fixed HEPA filters is well
      proven, the benefits of portable HEPA filters are still inconclusive. METHODS:
      This was a retrospective study to assess the impact of 48 portable HEPA filter
      units deployed in selected wards in Singapore General Hospital, an acute tertiary
      care hospital in Singapore. Data were extracted between December 2005 and June
      2008 on the diagnoses at discharge and microbiological and histological
      laboratory findings. All patients with possible, probable, or proven invasive
      aspergillosis (IA) were included. RESULTS: In wards with portable HEPA filters,
      the incidence rate of IA of 34.61/100,000 patient-days in the pre-installation
      period was reduced to 17.51/100,000 patient-days in the post-installation period
      (P = .01), for an incidence rate ratio of 1.98 (95% confidence interval [CI],
      1.10-2.97). In wards with no HEPA filters, there was no significant change in the
      incidence rate during the study period. Portable HEPA filters were associated
      with an adjusted odds ratio of 0.49 (95% CI, 0.28-0.85; P = .01), adjusted for
      diagnosis and length of hospital stay. CONCLUSIONS: Portable HEPA filters are
      effective in the prevention of IA. The cost of widespread portable HEPA
      filtration in hospitals will be more than offset by the decreases in nosocomial
      infections in general and in IA in particular.

PMID- 20129703
TI  - [Inflammatory bowel disease and pregnancy].
AB  - The coexistence of inflammatory bowel disease and pregnancy poses a major
      clinical challenge. The present article analyzes data on the mutual influence of
      the two entities, the effect of the disease and its pharmacological treatment on
      maternity, paternity, delivery and breast-feeding, the modifications that may be
      required during delivery, and the influence of the disease on fertility and
      sexuality, among other factors. The most important conclusions are the strong
      recommendation that inflammatory bowel disease be inactive when planning a
      pregnancy, that most drugs can be safely used (with the notorious exception of
      methotrexate, among others) and that reproduction does not need to be limited in
      these patients.

PMID- 20129704
TI  - [Immunology of celiac disease].
AB  - Celiac disease is an inflammatory disorder of the small intestine induced by
      intake of wheat gluten and other prolamines in genetically susceptible
      individuals. This disease is manifested by an increased number of intraepithelial
      and lamina propria lymphocytes, villous atrophy, tissue remodeling and the
      presence of anti-transglutaminase antibodies. The most widely accepted pathogenic
      model is based on adaptive immunity after T CD4(+)lymphocyte stimulation by
      tissue transglutamine-modified gluten peptides and HLA-DQ2/DQ8 restriction, which
      produce proinflammatory cytokines. Gluten also activates innate immunity and
      epithelial cytotoxicity mediated by intraepithelial lymphocytes. Although the
      effect of specific antibodies remains unclear, the availability of serological
      and immunogenetic markers as diagnostic tools has increased our knowledge of
      celiac disease and has led to a reevaluation of the diagnostic criteria,
      especially in adults with minimal or atypical disease expression.

PMID- 20129705
TI  - [Moroccan population perception of the Catalonian health system. Beliefs on
      health and disease].
AB  - OBJECTIVE: To describe the perception that the Moroccan population have of the
      Catalonian Health System. DESIGN: A cross-sectional, descriptive epidemiological
      study. SETTING: Social Institutions and the general Moroccan population in the
      city of Reus, Spain. PARTICIPANTS: A total of 150 people of Moroccan origin
      (50.8% females) from 33+/-13 years of age, were selected, of which 82.7% took
      part. METHOD: Evaluation of the perception of the Catalonian Health System using
      a questionnaire validated for the study, translated into Arabic. RESULTS: The
      majority of the Moroccan population believe that medications and vaccination
      programmes are effective, but also think that the disease depends on Allah (93.7%
      females and 95% males). The distrust of the husbands that their wives may be seen
      by male doctors increases (from 17.1% to 21.1%). As group they felt satisfied
      with the Spanish Health System (92.2% females and 86.7% males), had difficulties
      associated with language (51.6% females and 43.3% males) and, the males, in
      particular, found it difficult to keep appointments (50.8%). CONCLUSIONS: The
      majority of immigrants of Moroccan origin are satisfied with the health care
      received in Catalonia. The main difficulties they appear to have are keeping
      appointments and the language. The length of residence in Spain as regards the
      Moroccan population does not decrease the difficulties and differences in the
      Health System. This shows that education activities need to be promoted in the
      groups involved.

PMID- 20129706
TI  - [Factors involved in the development of the community projects. Observational
      study of the Catalonian primary care centers AUPA network].
AB  - OBJECTIVE: To describe the characteristics of the AUPA Health Centres network,
      identify the favourable elements and the obstacles when carrying out community
      projects (CP), the impact of belonging to the AUPA network, and the types of
      support members expect from the AUPA Network. DESIGN: A cross-sectional,
      descriptive and analytical study with analysis of information using quantitative
      and qualitative techniques. LOCATION: Primary Care. PARTICIPANTS: 15 centres of
      Primary Care belonging to the AUPA network before January 2006. PRINCIPAL
      MEASUREMENTS: Variables regarding the characteristics of the Health Centres,
      professionals, CP, facilitators and obstacles of the CP, usefulness, expectations
      and impact of belonging to the AUPA network. PRINCIPAL RESULTS: The majority of
      centres are teaching and receive methodological external support. The majority of
      CP are in initial phases of development and the most used methodology is
      Community Oriented Primary Care (COPC). The projects have the support of the
      community and intersectorial collaboration. Nursing is the group most involved.
      The factors that influence development of the CP are the motivation of the
      professionals, previous training in community care, management support and the
      participation of key personnel and the community. The community centres require
      more time to work on CP, methodological support from experts, better professional
      recognition, support by the Health Centre management and companies. CONCLUSIONS:
      It is necessary to motivate professionals, promote knowledge in community care,
      giving recognition and support by the institutions and by the community. Work
      benefits are perceived from the network: sharing experiences, commitment and
      gaining knowledge.

PMID- 20129707
TI  - ["Emergency contraception 2010"].

PMID- 20129708
TI  - [Implementation of preventive activities by family and community medicine
      residents in primary care clinics].
AB  - OBJECTIVE: To determine the level of preventive activities carried out by Family
      and Community Medicine medical residents during their stay in the Health Centre,
      as well as to estimate the time involved in carrying them out. DESIGN: Cross
      sectional, descriptive, observational study. SETTING: Teaching Health Centres in
      the Central- Cordoba and Guadalquivir Primary Care Districts. PARTICIPANTS: Forty
      medical residents and 384 clinical interviews with patients who were seen at the
      clinic. MAIN MEASUREMENTS: The consultations were video recorded and looked at by
      three medical residents who recorded the preventive activities carried out
      according to the 2005 PAPPS (Health Promotion and Disease Prevention Activities)
      recommendations, as well as the time employed in performing these activities.
      RESULTS: No preventive activities were performed in 72.1% (95% CI: 67.6 to 76.5%)
      of the consultations. The most frequent activities were secondary prevention
      (70.1%), mainly the taking of blood pressure (8.1%). The mean consultation time
      when there were no preventive activities carried out was 5.6 min (SD=3.1), whilst
      in those that did perform them it was 7.04 min (SD=3.05) (P<0.0001). CONCLUSIONS:
      The performing of preventive activities by medical residents in Primary Care
      clinics is very limited. A consultation that includes preventive activities
      requires a significantly longer time than in those that do not include them.

PMID- 20129709
TI  - [Maxillary osteonecrosis associated with the use of zoledronate: Presentation of
      three cases].

PMID- 20129710
TI  - [Filling in of the occupation in primary care clinical histories 1992-2007].

PMID- 20129711
TI  - [The shadow of "RALES" is long].

PMID- 20129712
TI  - [Clinical characteristics of patients under treatment for osteoporosis in a
      Primary Care Centre. Who do we treat?].
AB  - OBJECTIVES: To find out the clinical and demographic features of patients in
      treatment for osteoporosis, look for risk factors for osteoporosis and bone
      fractures, and assess whether treatment is indicated. DESIGN: Descriptive study
      of a series of cases. LOCATION: Primary Care Centre, Madrid. PARTICIPANTS: 216
      patients on treatment for osteoporosis during 2007. PRINCIPAL MEASURES:
      Sociodemographic variables, osteoporosis risk factors, risk of falling,
      prescription and treatment related information. To evaluate if treatment is
      indicated we have used principal medical guidelines. RESULTS: Most of our
      patients were Caucasian women with a mean age of 66.14 years. A total of 39.5%
      had suffered an osteoporotic fracture and 16.12% had family history of
      osteoporotic fracture. The majority of our registers,73.15%, do not report
      information on Dual-Energy X-ray Absorptiometry (DEXA), and 73.13% do not make
      any reference to bone mineral density. Risk factors are not recorded in most of
      the clinical histories. Only 51.85% of the treatments were well indicated, and
      44% of them began at a primary health care centre. CONCLUSIONS: Nearly 50% of
      treatments are not well indicated and a high percentage of our clinical histories
      do not record risk factors correctly. We should improve our clinical histories,
      as we are responsible for identifying, studying, evaluating, treating and
      controlling the progress of osteoporosis.

PMID- 20129713
TI  - [Reducing stress levels and anxiety in primary-care physicians through training
      and practice of a mindfulness meditation technique].
AB  - PURPOSE: To check the effectiveness of a mindfulness development meditation
      technique on stress and anxiety in a group of primary-care physicians. DESIGN:
      Quasi-experimental with pretest/posttest/follow-up measurements in a control
      group and an experimental group. SITE: University of Almeria. PARTICIPANTS: 38
      primary-care physicians enrolled in a Teaching Aptitude Course (CAP).
      INTERVENTION: An experimental group and a control group were formed with 19
      participants in each. The experimental group took a psycho-educational meditation
      program for training and practice in mindfulness. MEASUREMENT: The Perceived
      Stress Scale (PSS), the Strain Questionnaire and the State-Trait Anxiety
      Questionnaire were used to measure stress and anxiety levels. RESULTS: A
      comparative statistical analysis was performed using the Mann-Whitney non
      parametric U test, finding a significant reduction in all the primary-care
      physician stress and anxiety variables in the experimental group compared to the
      control group in pretest-posttest and follow-up tests. CONCLUSIONS: The results
      of this study support the effectiveness of mindfulness development meditation
      techniques in decreasing stress and anxiety in primary-care physicians.
      Nevertheless, the study shows various limitations that would have to be corrected
      in successive studies to bring more validity to the results.

PMID- 20129714
TI  - [Findings of lung ventilation-perfusion SPECT-CT study in a case of pulmonary
      thromboembolism in a child].

PMID- 20129715
TI  - [Angiosarcoma of the scalp: extension study with PET-CT].

PMID- 20129716
TI  - Characteristics and outcome of HIV infection in gypsies in the Spanish VACH
      Cohort.
AB  - OBJECTIVE: To study the characteristics of HIV infection in the gypsy (Roma)
      population in Spain, as compared with those of the Caucasian, non-gypsy majority.
      DESIGN: Cross-sectional, historical cohort study from the Spanish VACH Cohort.
      METHODS: Patients attending VACH clinics between 1 June 2004 and 30 November 2004
      were classified according to their racial and ethnic origin as "gypsies",
      Caucasian non-gypsy Spanish natives (CNGN), and "other" (the last being excluded
      from this study). Their sociodemographic and clinico-epidemiological
      characteristics were compared, as well as the Kaplan-Meier curves of time to
      AIDS, or death, or disease progression (either of the 2 outcomes). RESULTS: 4819
      (48%) of 10,032 cases included in the VACH database were eligible: 210 (4.2%)
      were gypsies and 4252 (84.8%) were CNGN. Differences were observed in age,
      household, academic, inmate, marital, and employment history. Injecting drug use
      had been the most frequent mechanism of transmission in both groups, but to a
      greater extent among gypsies (72% versus 50%; P<0.000). Sex distribution, CD4
      cell counts, and viral loads at the first visit were similar in the 2 groups, as
      was the percentage of patients with previous AIDS, percentage receiving
      antiretrovirals, and percentage subsequently starting antiretroviral therapy. Up
      to 1 April 2005, 416 new AIDS cases and 85 deaths were recorded. The percentage
      of these outcomes did not differ between groups, but log-rank test showed a
      shorter time to AIDS and disease progression among gypsies. CONCLUSIONS: The
      sociodemographic characteristics of gypsies, the largest minority in the VACH
      Cohort, show differences relative to those of CNGN. HIV-related outcomes suggest
      that gypsies have a poorer prognosis.

PMID- 20129717
TI  - A rationale for the activity profile of arylpiperazinylthioalkyls as 5-HT1A
      serotonin and alpha1-adrenergic receptor ligands.
AB  - The 5-HT1A and alpha1-receptor binding affinities of the arylpiperazinylthioalkyl
      derivatives have been quantitatively expressed in terms of topological and
      molecular features. The analysis revealed that a lower value of atomic
      composition based index (AAC), higher values of structural information content
      (SIC3) and topological charge index (GGI9) would be beneficial to the 5-HT1A
      receptor binding. For the alpha1-receptor binding affinity the higher values of
      topological charge index (GGI9) and atomic Sanderson electronegativities weighted
      descriptor (GATS3e) and more number of hydrogen atoms attached to sp or sp3
      hybridized carbon atoms in a molecular structure (H-047) would be favorable. The
      derived significant models may further be used to synthesize new potential and
      selective compounds.

PMID- 20129718
TI  - Novel cyclic-imide peptidomimetics as aminopeptidase N inhibitors. Structure
      based design, chemistry and activity evaluation. II.
AB  - A novel class of potent aminopeptidase N inhibitors with 3-amino-cyclic-imide
      scaffold is described. The preliminary biological test revealed that all the
      compounds displayed high specific inhibitory activity against aminopeptidase N
      compared with previous work because of the existence of free amino group.
      Compounds containing hydroxamate group are more potent than carboxyl and ester
      derivatives. Compound 13f potentially inhibited APN activity with IC(50) value of
      1.8 microM and displayed specific activity profiles in cells assay and in vivo
      anti-metastasis assay.

PMID- 20129719
TI  - Design and synthesis of novel 3,4-disubstituted pyrazoles for nanomedicine
      applications against malignant gliomas.
AB  - A series of novel 3,4-disubstituted pyrazoles were synthesized. The cytotoxicity
      against U87MG glioma cell line have been investigated in vitro and three of these
      compounds showed promising inhibitory activity on cell growth with an IC50 lower
      than 90 microM. AutoDock molecular docking into type I TGF-beta receptor (TGF
      beta-RI; PDB: 1py5) has been done for lead optimization of the mentioned
      compounds as potential TGF-beta-RI1 inhibitors. In particular, 3-aryl-4-amido
      pyrazole containing long omega-amino-aliphatic chain emerged as a good candidate
      for further optimization. Entrapment into targetable PEG-based micelles improved
      growth inhibition IC50 values up to 100 nM and this could lead to a novel drug
      delivery strategy for treating glioblastoma.

PMID- 20129720
TI  - Time spent studying on a pre-registration nursing programme module: an
      exploratory study and implications for regulation.
AB  - European Union (EU) regulations require that university programmes are of
      specified duration. Additional EU regulations apply specifically to university
      based nurse education, enacted in the UK by the Nursing and Midwifery Council
      (NMC). However, little is known about how much time student nurses spend on their
      studies. In this exploratory study, students undertaking a single module in the
      pre-registration diploma programme at an English university were asked to keep a
      log of learning activity for the duration of the module. Twenty-six students
      completed the log. These students achieved higher grades and attended more
      lectures than the average for the module. The mean study time was 128.4 h against
      a regulatory assumption that the module should take 200 h. More than half of the
      26 students undertook paid work during the module run, though this work was not
      associated with poorer performance. Problems in regulation for course duration
      are discussed and it is suggested that undertaking a 4600 h course in 3 years is
      problematic. More research is required so that patterns of study can be better
      understood and student centred programmes meeting regulatory requirements
      developed.

PMID- 20129721
TI  - What is provided and what the registered nurse needs--bioscience learning through
      the pre-registration curriculum.
AB  - Registered nurses undertaking programmes of study to become non-medical
      prescribers appear to have limited biological science knowledge. A case study was
      undertaken to determine whether the nurses entering Prescriber programmes
      considered studies in bioscience in their pre-registration nursing courses had
      been sufficient, linked to practice, and had prepared them for their roles as
      registered nurses. The literature identifies a continuing trend amongst nursing
      students describing a lack of sufficient bioscience in initial nurse education;
      there is limited literature on the views of experienced registered nurses. The
      participants in this study were 42 registered nurses from adult and mental health
      nursing, community and inpatient services. The results obtained from
      questionnaires and interviews are described. Questionnaire analysis identified
      that 57.1% of participants indicated bioscience in their pre-registration nursing
      programme had been limited and 40.5% stated the bioscience content had not
      prepared them for their roles on registration. Those reporting extensive coverage
      of bioscience were all aged over 41 years and had qualified before 1995. Greatest
      coverage of bioscience in pre-registration programmes was reported in relation to
      anatomy and physiology, with relatively limited coverage of microbiology,
      pharmacology or biochemistry. Respondents considered all five topics to be
      important. Interviews supported the questionnaire findings.

PMID- 20129722
TI  - Violence experienced by Turkish nursing students in clinical settings: their
      emotions and behaviors.
AB  - AIM: This descriptive study aimed to determine the violence experiences of
      nursing students' in clinical settings, the types of violence, and the way their
      behaviors and emotions are affected after such an experience. BACKGROUND: The
      risk of being subjected to violence among health staff is very high and the
      students who worked in the same kind of work environments also faced similar
      risks. METHODS: The data of the study were obtained from the 380 nursing students
      who were studying at 2nd, 3rd, and 4th grades. Participation was voluntary. A
      questionnaire form was developed by the researchers and distributed to the
      students. RESULTS: It was found that 50.3% of the students were subjected to
      violence, and 91.6% of these students were subjected to verbal violence. The
      students most frequently experienced anger, fury, and enmity (84.3%) after
      confronting violence. CONCLUSION: Findings of our study showed that similar to
      nurses, nursing students, who spent a significant proportion of their education
      in areas of practice, also experienced violence. Therefore, measures should be
      taken to prevent the violence inflicted upon nursing students in clinical
      settings, and nursing students should be provided with information related to
      communication and the coping methods with violence during their education.

PMID- 20129723
TI  - Review of the radial free flap: still evolving or facing extinction? Part two:
      osteocutaneous radial free flap.
AB  - The osteocutaneous radial flap is robust, reliable, and relatively simple to
      harvest, which will ensure that it remains one of the established reconstructive
      options in most maxillofacial units. Evidence based on clinical observational
      studies and biomechanical studies supports the routine or selective use of
      prophylactic internal fixation to strengthen the radial osteocutaneous donor
      site. This allows safe harvesting of the maximum volume of available bone, up to
      half of the circumference, with minimal risk of fracture or long term
      complications. The incidence of fracture with the plate placed either anteriorly
      or posteriorly is equally low, but the anterior position is technically easier
      and probably less likely to cause additional morbidity. This approach probably
      produces the least morbidity that may currently be achieved when managing the
      inherent flaws of the radial hard tissue donor site. The introduction of
      prophylactic internal fixation consolidates the role of the osteocutaneous radial
      flap for repair of defects that require a relatively small volume of bone and an
      appreciable area of thin soft tissue, particularly when a long vascular pedicle
      is desirable. This includes low level defects of the maxilla, some defects of the
      mandible, and niche reconstructions, such as the orbital rim. It remains useful
      as a first choice of flap when there is appreciable peripheral vascular disease,
      when there are other serious coexisting medical conditions; if it is the
      preferred choice of the patient for functional reasons such as mobility of the
      lower limb or hip, and as a salvage flap when other reconstructive options have
      been exhausted.

PMID- 20129724
TI  - Atypical fibroxanthoma: Case series of 16 patients.
AB  - Atypical fibroxanthoma is an unusual tumour of skin seen mainly in the head and
      neck region of elderly patients. Clinically it appears as red, ulcerated nodules,
      which can be difficult to differentiate from other tumours without
      histopathological examination. Immunohistochemical analysis also aids diagnosis.
      The mainstay of treatment is operation. We present a case series of 16 patients
      with 17 atypical fibroxanthomas over a 5-year period in a district general
      hospital.

PMID- 20129725
TI  - Three-dimensional stereoradiographic modeling of rib cage before and after spinal
      growing rod procedures in early-onset scoliosis.
AB  - BACKGROUND: Early-onset scoliosis frequently leads to major thoracic deformity
      and pulmonary restrictive disease. Growing rods surgical techniques were
      developed to achieve a satisfactory correction of the spinal curves during
      growth. The effect on the rib cage deformity has not yet been documented. The
      purpose of this study was to analyze the changes of the thoracic geometry after
      implantation of a growing rod, and to evaluate a stereoradiographic
      reconstruction method among young scoliotic patients. METHODS: Four patients were
      enrolled in the study, and four additional patients in the reproducibility study.
      Three-dimensional spine and rib cage models were generated after low-dose
      stereoradiographic imaging (EOS). Three-dimensional parameters were computed
      before and after surgery. Intra and inter-observer reproducibility was
      calculated, and the accuracy was assessed in comparison to volumetric CT-scan.
      FINDINGS: The average Cobb angle was reduced from 50.8 degrees to 26 degrees .
      The surgery resulted in a complex 3D effect on the rib cage, combining frontal,
      lateral, and axial rotation. This effect was dependent of the side (concave or
      convex), and the position relative to the apical vertebra. Mean errors in
      comparison to CT-scan were 3.5mm. INTERPRETATION: The results on the spinal
      deformity are comparable to other series. The effect on the rib cage is of a
      smaller magnitude than in the case of a spinal arthrodesis. A longer follow-up is
      necessary to confirm the positive effect on the rib cage deformity. Further
      research should be performed to improve the reproducibility of 3D parameters.

PMID- 20129726
TI  - Primary stability of custom and anatomical uncemented femoral stems: a method for
      three-dimensional in vitro measurement of implant stability.
AB  - BACKGROUND: Lack of primary stability of cementless hip stems prevents bone
      ingrowth and may lead to loosening of the stem. Direct measures of the implant
      stability require drilled holes in the bone at the measuring site. These holes
      weaken the cortical bone, limit the number of possible measuring points and
      inhibit other biomechanical measurements. This in vitro study aimed to develop a
      method for indirect measurement of primary stability of femoral stems, leaving
      the specimen intact. The method was used to compare the primary stability of two
      uncemented femoral stems with different proximal fit and fill and different stem
      length. METHODS: An in vitro method for indirect full three-dimensional
      measurement of implant-bone interface motion was developed. Uncemented customized
      (n=10) and anatomical stems (n=10) were inserted in human cadaver femora and the
      primary stability during one leg stance and stair climbing was measured.
      FINDINGS: The method had high precision, and the errors due to necessary
      assumption of rigid body components were minimal. The customized stem with
      optimal proximal fit and fill provided the best initial stability for rotation in
      retroversion. The anatomical stem with longer stem length was more resistant to
      permanent rotation in varus. INTERPRETATION: During stem design development the
      primary stability can be measured at all wanted measuring sites with the
      presented method, leaving the specimen intact for further analyses.

PMID- 20129727
TI  - Biomechanical study of posterior wall acetabular fracture fixation using
      acetabular tridimensional memory alloy-fixation system.
AB  - BACKGROUND: We developed the acetabular tridimensional memory alloy-fixation
      system (ATMFS), which is made of NiTi shape memory alloy, according to the
      specific mechanical properties of biological memory material, nitinol alloy and
      measured distribution of contact area and pressure between the acetabulum and the
      femoral head of cadaveric pelvis. METHODS: Six formalin-preserved cadaveric
      pelvis were used for this investigation. Pressure-sensitive film was used to
      measure contact area and pressure within the anterior, superior, and posterior
      regions of the acetabulum. The pelvis were loaded under the following four
      conditions: (1) intact; (2) following a creation posterior wall fracture defect;
      (3) following reduction and standard internal fixation with reconstruction plate;
      (4) following reduction and internal fixation with a new shape memory alloy
      device named ATMFS. A posterior wall fracture was created along an arc of 40-90
      degrees about the acetabular rim. FINDINGS: Creation of a posterior wall defect
      resulted in increased load in the superior acetabulum (1422N) as compared to the
      intact condition (762N, P=0.007). Following reduction and internal fixation, the
      load distributed to the superior acetabulum (1486N) was not statistically
      different from the defect condition. Following the fixation with ATMFS, the load
      seen at the superior region of the actabulum (936N) was less than fixation with
      reconstruction plate and was not different from intact state (P=0.4).
      INTERPRETATION: These data indicate that the use of ATMFS as a fracture internal
      fixation device resulted a partial restoration of joint loading parameters toward
      the intact state. ATMFS fixation may result in a clinical benefit.

PMID- 20129728
TI  - Nonlinear and anisotropic tensile properties of graft materials used in soft
      tissue applications.
AB  - BACKGROUND: The mechanical properties of extracellular matrix grafts that are
      intended to augment or replace soft tissues should be comparable to the native
      tissue. Such grafts are often used in fiber-reinforced tissue applications that
      undergo multi-axial loading and therefore knowledge of the anisotropic and
      nonlinear properties are needed, including the moduli and Poisson's ratio in two
      orthogonal directions within the plane of the graft. The objective of this study
      was to measure the tensile mechanical properties of several marketed grafts:
      Alloderm, Restore, CuffPatch, and OrthADAPT. METHODS: The degree of anisotropy
      and non-linearity within each graft was evaluated from uniaxial tensile tests and
      compared to their native tissue. FINDINGS: The Alloderm graft was anisotropic in
      both the toe- and linear-region of the stress-strain response, was highly
      nonlinear, and generally had low properties. The Restore and CuffPatch grafts had
      similar stress-strain responses, were largely isotropic, had a linear-region
      modulus of 18MPa, and were nonlinear. OrthADAPT was anisotropic in the linear
      region (131 MPA vs 47MPa in the toe-region) and was highly nonlinear. The Poisson
      ratio for all grafts was between 0.4 and 0.7, except for the parallel orientation
      of Restore which was greater than 1.0. INTERPRETATION: Having an informed
      understanding of how the available grafts perform mechanically will allow for
      better assessment by the physician for which graft to apply depending upon its
      application.

PMID- 20129729
TI  - Degradation of trichloroethylene by Fe(II) chelated with cross-linked chitosan in
      a modified Fenton reaction.
AB  - Degradation of trichloroethylene (TCE) by a modified Fenton reaction was
      investigated in aqueous solution. Fenton reaction can be significantly enhanced
      in the presence of Fe(II) chelated by cross-linked chitosan (CS) with
      glutaraldehyde (GLA) at neutral pH. A remarkable oxidative degradation of TCE
      (1.838 h(-1)) was observed in the modified Fenton system with Fe(II)-CS/GLA (10
      mM and 2 g L(-1), respectively) and H(2)O(2) (318 mM), while no significant
      degradation (0.005 h(-1)) was observed in the classic Fenton reaction system with
      Fe(II) (10 mM) and H(2)O(2) (318 mM) at pH 7 in 5 h. The kinetic rate constants
      for the degradation of TCE in the modified Fenton system was dependent on the
      initial suspension pH, Fe(II) loading, CS/GLA dosage, and concentration of
      H(2)O(2). We observed the formation of surface Fe(II)-CS/GLA complex using
      microscopic analyses and identified Fe oxidation (Fe(II) to Fe(III)) coupled with
      H(2)O(2) reduction on the Fe(II)-CS/GLA surfaces during the modified Fenton
      reaction.

PMID- 20129730
TI  - Hydrometallurgical process for zinc recovery from electric arc furnace dust
      (EAFD): part I: Characterization and leaching by diluted sulphuric acid.
AB  - The present paper is the first of a series of two articles dealing with the
      development of an integrated process for the recovery of zinc from electric arc
      furnace dust (EAFD), a hazardous industrial waste generated in the collection of
      particulate material during steelmaking process via electric arc furnace. Part I
      presents the EAFD characterization and its leaching process by diluted sulphuric
      acid, whereas Part II deals with the purification of the leach liquor and the
      recovery of zinc by solvent extraction/electrowinning. The characterization of
      the examined electric arc furnace dust was carried out by using granulometry
      analysis, chemical analysis, X-ray diffraction (XRD),
      thermogravimetric/differential thermal analysis (TG/DTA) and scanning electron
      microscopy (SEM). The leaching process was based on the Zn extraction with
      diluted sulphuric acid from EAFD under atmospheric conditions and without using
      any preliminary treatment. Statistical design and analysis of experiments were
      used, in order to determine the main effects and interactions of the leaching
      process factors, which were: acid normality, temperature and solid to liquid
      ratio. The zinc recovery efficiency on the basis of EAFD weight reached 80%. X
      ray diffraction and scanning electron microscopy were used for the
      characterization of the leached residues.

PMID- 20129731
TI  - The application of zero-valent iron nanoparticles for the remediation of a
      uranium-contaminated waste effluent.
AB  - Zero-valent iron nanoparticles (INP) were investigated as a remediation strategy
      for a uranium-contaminated waste effluent from AWE, Aldermaston. Nanoparticles
      were introduced to the effluent, under both oxic and anoxic conditions, and
      allowed to react for a 28-d period during which the liquid and nanoparticle
      solids were periodically sampled. Analysis of the solution indicated that under
      both conditions U was removed to <1.5% of its initial concentration within 1h of
      introduction and remained at similar concentrations until approximately 48 h. A
      rapid release of Fe into solution was also recorded during this initial period;
      attributed to the limited partial dissolution of the INP. XPS analyses of the
      reacted nanoparticulate solids between 1 and 48 h showed an increased
      Fe(III):Fe(II) ratio, consistent with the detection of iron oxidation products
      (akaganeite and magnetite) by XRD and FIB. XPS analysis also recorded uranium on
      the recovered particulates indicating the chemical reduction of U(VI) to U(IV)
      within 1h. Following the initial retention period U-dissolution of U was recorded
      from 48 h, and attributed to reoxidation. The efficient uptake and retention of U
      on the INP for periods up to 48 h provide proof that INP may be effectively used
      for the remediation of complex U-contaminated effluents.

PMID- 20129732
TI  - Biodegradation of propionitrile by Klebsiella oxytoca immobilized in alginate and
      cellulose triacetate gel.
AB  - A microbial process for the degradation of propionitrile by Klebsiella oxytoca
      was studied. The microorganism, K. oxytoca, was isolated from the discharged
      wastewater of metal plating factory in southern Taiwan and adapted for
      propionitrile biodegradation. The free and immobilized cells of K. oxytoca were
      then examined for their capabilities on degrading propionitrile under various
      conditions. Alginate (AL) and cellulose triacetate (CT) techniques were applied
      for the preparation of immobilized cells. The efficiency and produced metabolic
      intermediates and end-products of propionitrile degradation were monitored in
      bath and continuous bioreactor experiments. Results reveal that up to 100 and 150
      mM of propionitrile could be removed completely by the free and immobilized cell
      systems, respectively. Furthermore, both immobilized cell systems show higher
      removal efficiencies in wider ranges of temperature (20-40 degrees C) and pH (6
      8) compared with the free cell system. Results also indicate that immobilized
      cell system could support a higher cell density to enhance the removal efficiency
      of propionitrile. Immobilized cells were reused in five consecutive degradation
      experiments, and up to 99% of propionitrile degradation was observed in each
      batch test. This suggests that the activity of immobilized cells can be
      maintained and reused throughout different propionitrile degradation processes. A
      two-step pathway was observed for the biodegradation of propionitrile.
      Propionamide was first produced followed by propionic acid and ammonia. Results
      suggest that nitrile hydratase and amidase were involved in the degradation
      pathways of K. oxytoca. In the continuous bioreactor, both immobilized cells were
      capable of removing 150 mM of propionitriles completely within 16h, and the
      maximum propionitriles removal rates using AL and CT immobilized beads were 5.04
      and 4.98 mM h(-1), respectively. Comparing the removal rates obtained from batch
      experiments with immobilized cells (AL and CT were 1.57 and 2.18 mM h(-1) at 150
      mM of propionitrile, respectively), the continuous-flow bioreactor show higher
      potential for practical application.

PMID- 20129733
TI  - Simulation and assessment of SO2 toxic environment after ignition of uncontrolled
      sour gas flow of well blowout in hills.
AB  - To study the sulfur dioxide (SO(2)) toxic environment after the ignition of
      uncontrolled sour gas flow of well blowout, we propose an integrated model to
      simulate the accident scenario and assess the consequences of SO(2) poisoning.
      The accident simulation is carried out based on computational fluid dynamics
      (CFD), which is composed of well blowout dynamics, combustion of sour gas, and
      products dispersion. Furthermore, detailed complex terrains are built and
      boundary layer flows are simulated according to Pasquill stability classes. Then
      based on the estimated exposure dose derived from the toxic dose-response
      relationship, quantitative assessment is carried out by using equivalent
      emergency response planning guideline (ERPG) concentration. In this case study,
      the contaminated areas are graded into three levels, and the areas, maximal
      influence distances, and main trajectories are predicted. We show that wind
      drives the contamination and its distribution to spread downwind, and terrains
      change the distribution shape through spatial aggregation and obstacles. As a
      result, the most dangerous regions are the downwind areas, the foot of the
      slopes, and depression areas such as valleys. These cause unfavorable influences
      on emergency response for accident control and public evacuation. In addition,
      the effectiveness of controlling the number of deaths by employing ignition is
      verified in theory. Based on the assessment results, we propose some suggestions
      for risk assessment, emergency response and accident decision making.

PMID- 20129734
TI  - A cure for back pain?

PMID- 20129735
TI  - Performance-dependent inhibition of pain by an executive working memory task.
AB  - It is widely assumed that distraction reduces pain. Similarly, it is assumed that
      pain distracts from concurrent, unrelated cognitive processing, reducing
      performance on difficult tasks. Taken together, these assumptions suggest pain
      processing and cognitive function engage an overlapping set of domain-general,
      capacity-limited mental resources. However, experimental tests of this proposal
      have yielded mixed results, leading to alternative proposals that challenge the
      common model of a bidirectional relationship between concurrent pain and task
      performance. We tested these contrasting positions using a novel concurrent pain
      and executive working memory paradigm. Both task difficulty and nociceptive
      stimulus intensity were individually calibrated for each participant.
      Participants reported less pain during the working memory task than a visually
      matched control condition. Conversely, increasing levels of heat incrementally
      reduced task performance. Path analyses showed that variations in pain completely
      mediated this effect, and that even within a given heat level, trial-by-trial
      fluctuations in pain predicted decrements in performance. In sum, these findings
      argue that overlapping cognitive resources play a role in both pain processing
      and executive working memory. Future studies could use this paradigm to
      understand more precisely which components of executive function or other
      cognitive resources contribute to the experience of pain.

PMID- 20129737
TI  - Thyroid axis activity and suicidal behavior in depressed patients.
AB  - The aim of this study was to investigate the relationship between suicidal
      behavior and hypothalamic-pituitary thyroid (HPT) axis activity in depressed
      patients. The serum levels of thyrotropin (TSH), free thyroxine (FT4), and free
      triiodothyronine (FT3) were evaluated before and after 0800 and 2300 h
      thyrotropin-releasing hormone (TRH) challenges, on the same day, in 95 medication
      free DSM-IV euthyroid major depressed inpatients and 44 healthy hospitalized
      controls. Compared to controls: (1) patients with a positive suicide history
      (PSH; n=53) showed lower basal FT4 (at 0800 h: p<0.005; at 2300 h: p<0.03), but
      normal FT3 levels, while patients with a negative suicide history (NSH; n=42)
      showed normal FT4 and FT3 levels; (2) TSH responses to TRH (DeltaTSH) were
      blunted in NSHs (at 0800 h: p<0.03; at 2300 h: p<0.00001), but not in PSHs; (3)
      both NSHs and PSHs showed lower DeltaDeltaTSH values (differences between 2300 h
      DeltaTSH and 0800 h-DeltaTSH) (p<0.000001 and p<0.003, respectively). Compared to
      NSHs, basal FT4 levels were reduced in PSHs (at 0800 h: p<0.002; at 2300h:
      p<0.006). HPT parameters were not significantly different between recent suicide
      attempters (n=32) and past suicide attempters (n=21). However, compared to
      controls, recent suicide attempters showed lower 2300 h-DeltaTSH (p<0.04) and
      DeltaDeltaTSH (p<0.002) values, and lower basal FT4 values (at 0800 h: p<0.006;
      at 2300 h: p<0.02). Our results, obtained in a large sample of depressed
      inpatients, indicate that various degrees of HPT axis dysregulation are
      associated with the history of suicide.

PMID- 20129736
TI  - Agonistic behavior in males and females: effects of an estrogen receptor beta
      agonist in gonadectomized and gonadally intact mice.
AB  - Affiliative and agonistic social interactions are mediated by gonadal hormones.
      Research with estrogen receptor alpha (ERalpha) or beta (ERbeta) knockout (KO)
      mice show that long-term inactivation of ERalpha decreases, while inactivation of
      ERbeta increases, male aggression. Opposite effects were found in female
      alphaERKO and betaERKO mice. The role of acute activation of ERalpha or ERbeta in
      the agonistic responses of adult non-KO mice is unknown. We report here the
      effects of the ERbeta selective agonist WAY-200070 on agonistic and social
      behavior in gonadally intact and gonadectomized (gonadex) male and female CD-1
      mice towards a gonadex, same-sex intruder. All 15min resident-intruder tests were
      videotaped for comprehensive behavioral analysis. Separate analyses assessed: (1)
      effects of WAY-200070 on each sex and gonadal condition; (2) differences between
      sexes, and between gonadally intact and gonadex mice, in untreated animals.
      Results show that in gonadally intact male and female mice, WAY-200070 increased
      agonistic behaviors such as pushing down the intruder and aggressive grooming,
      while leaving attacks unaffected. In untreated mice, males attacked more than
      females, and gonadex animals showed less agonistic behavior than same-sex,
      gonadally intact mice. Overall, our detailed behavioral analysis suggested that
      in gonadally intact male and female mice, ERbeta mediates patterns of agonistic
      behavior that are not directly involved in attacks. This suggests that specific
      aspects of aggressive behavior are acutely mediated by ERbeta in adult mice. Our
      results also showed that, in resident-intruder tests, female mice spend as much
      time in intrasexual agonistic interactions as males, but use agonistic behaviors
      that involve extremely low levels of direct attacks. This non-attack aggression
      in females is increased by acute activation of ERbeta. Thus, acute activation of
      ERbeta similarly mediates agonistic behavior in adult male and female CD-1 mice.

PMID- 20129738
TI  - Exogenous cortisol enhances aggressive behavior in females, but not in males.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis plays a major role in the
      development, elicitation, and enhancement of aggressive behavior in animals.
      Increasing evidence suggests that this is also true for humans. Here, we report
      on a study of the role of basal and acute HPA axis activity in a sample of 48
      healthy male and female adults. We pharmacologically enhanced cortisol levels and
      used the Taylor Aggression Paradigm (TAP) to induce and measure aggression
      (divided into three blocks). Participants either received an oral dose of 20 mg
      hydrocortisone (cortisol group) or a placebo (placebo group). Half of each group
      received high or low levels of provocation with the TAP, respectively. Before, we
      assessed the cortisol awakening response as a trait measure of basal HPA axis
      activity. Participants in the cortisol group reacted more aggressively in the
      third block of the TAP compared to the placebo group. Furthermore, gender
      interacted with treatment: only females, but not males showed enhanced aggressive
      behavior after cortisol administration. There was no significant difference in
      males between the placebo and cortisol group. Basal HPA axis activity was
      negatively related to aggressive behavior, but again only in females and most
      strongly within the placebo group. This study provides the first evidence for a
      causal involvement of acute HPA axis activation in aggressive behavior in humans.

PMID- 20129739
TI  - Post concussion syndrome: the attraction of the psychological by the organic.
AB  - Post concussion symptoms following mild traumatic brain injury are a difficult
      clinical state to conceptualise. The constellation of symptoms include those with
      an organic signature (and presumed organic aetiology), and those with overt
      psychological features. A seemingly trivial head injury may result in enduring
      symptoms. The validity of post concussion syndrome (PCS) has been the focus of
      much medico-legal debate, as has its cause. Whether PCS is 'neurogenic' or
      'psychogenic' in aetiology remains contestable. Babinski, in 1918, hypothesised
      that an organic factor initiated the symptoms of the disorder now known as PCS,
      and that this acted as a 'bait', or attractor, for pre-existing and post-injury
      psychological influences. This hypothesis, which has been neither proven nor
      disproven over the subsequent nearly one hundred years, deserves reconsideration
      for it is an appealing model of PCS.

PMID- 20129740
TI  - Controllable metastasis: the trap for the esophageal cancer cells?
AB  - The prognosis of esophageal cancer (EC) remains poor, lymph node metastasis is
      one of the most important factors for determining the prognosis of patients with
      EC. Extensive lymph node dissection has long been considered as the favorable
      procedure to achieve an accurate pathologic staging and a better prognosis.
      However, the effect of extensive lymphadenectomy during esophagectomy on survival
      of EC patients has been doubted. Herein we present the hypotheses that the
      selective lymphadenectomy might be a potential strategy for EC by creating the
      traps of cancer cells. Once metastatic cancer cells immersed in, patients will
      acquire remarkable survival profit by surgical removal these traps.

PMID- 20129741
TI  - Circulating free fetal nucleic acids in maternal plasma and preeclampsia.
AB  - Although preeclampsia represents a major threat for many pregnant women, the
      pathogenesis of this complication is far from being clear. Recent studies suggest
      that preeclampsia is an autoimmune disorder. Auto-antibodies against angiotensin
      receptor might explain some of the pathologic findings associated with
      preeclampsia. However, the origin of the autoimmune reaction is unknown. Here we
      hypothesize that circulating fetal RNA in maternal plasma might transfect
      maternal cells. Expression of fetal specific sequences could lead to an immune
      reaction breaking the immune tolerance against some antigens. Male fetus bearing
      pregnancies could be at higher risk of preeclampsia due to expression of Y
      specific transcripts. This hypothesis is testable by analyzing antibodies and T
      lymphocytes of pregnant women with male and female fetuses.

PMID- 20129742
TI  - Development of a multi-locus sequence typing scheme for avian isolates of
      Pasteurella multocida.
AB  - A total of 63 isolates of Pasteurella multocida from Australian poultry, all
      associated with fowl cholera outbreaks, and three international reference
      strains, representing the three subspecies within P. multocida were used to
      develop a multi-locus sequence typing scheme. Primers were designed for conserved
      regions of seven house-keeping enzymes -adk, est, gdh, mdh, pgi, pmi and zwf -
      and internal fragments of 570-784 bp were sequenced for all isolates and strains.
      The number of alleles at the different loci ranged from 11 to 20 and a total of
      29 allelic profiles or sequence types were recognised amongst the 66 strains.
      There was a strong concordance between the MLST data and the existing multi-locus
      enzyme electrophoresis and ribotyping data. When used to study a sub-set of
      isolates with a known detailed epidemiological history, the MLST data matched the
      results given by restriction endonuclease analysis, pulsed-field gel
      electrophoresis, ribotyping and REP-PCR. The MLST scheme provides a high level of
      resolution and is an excellent tool for studying the population structure and
      epidemiology of P. multocida.

PMID- 20129743
TI  - Adipokines in breast milk and preterm infants.
AB  - Studies have shown that the early life environment affects feeding behaviour,
      food intake and energy balance in later life, suggesting there is a link between
      foetal and infant growth and the risk of metabolic disorders in adulthood.
      Although there is an evident epidemiological association between low birth weight
      and adult-onset diseases, the incidence of metabolic diseases in adulthood among
      people who were born prematurely is still unknown. Considerable advances have
      been made during the last years in the scientific knowledge of the benefits of
      early nutrition, such as breastfeeding, on health and well-being later in life.
      Nutritional researchers have focussed their attention on the biological
      characteristics of human breast milk, which represents the main source of
      nutrients in the first months of life for breastfed infants. Recently, leptin and
      ghrelin have been detected in the breast milk of mothers of term and preterm
      infants. Adiponectin and resistin, present in term human milk, have not been
      investigated in the breast milk of mothers of preterm infants. These hormones are
      involved in the regulation of energy balance and may have a role in the
      regulation of growth and development in the neonatal period and infancy, as well
      as long-term effects on metabolic programming. Leptin, adiponectin and resistin
      have been found at lower levels in pre-term infants compared with term newborns,
      whereas there seems to be no difference in ghrelin levels. Future research is
      necessary to clarify the role of hormones present in breast milk for identifying
      potential short- and long-term effects of breastfeeding on the health of children
      born prematurely.

PMID- 20129744
TI  - Active immunization with recombinant GnRH fusion protein in boars reduces both
      testicular development and mRNA expression levels of GnRH receptor in pituitary.
AB  - Immunization using recombinant maltose binding protein-gonadotropin releasing
      hormone (MBP-GnRH6) altered both testicular development and transcription of the
      pituitary GnRH receptor (GnRHR) gene in boars. Scrotal measurement and blood
      samples were taken at 4-week interval after immunization at 9 weeks of age. The
      concentrations of testosterone and anti-GnRH antibodies in serum were determined
      by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The
      results showed that active immunization with MBP-GnRH6 increased the serum
      concentration of anti-GnRH antibodies (P<0.05) and reduced the serum
      concentration of testosterone (P<0.05) as compared with MBP controls. At 25 weeks
      of age, boars were sacrificed and testes were evaluated histologically.
      Testicular development was suppressed in the MBP-GnRH6 immunized animals as
      compared with MBP immunized boars. MBP-GnRH6 immunized pigs exhibited mounting
      behavior 4 weeks later than MBP immunized boars. No mature spermatozoa were
      observed from MBP-GnRH6 immunized animals. By real-time quantitative PCR
      analysis, the amount of GnRHR mRNA in the pituitary tissue was found to be
      significantly lower in MBP-GnRH6 immunized animals than in controls (P<0.05).
      These data demonstrate that recombinant MBP-GnRH6 was effective in immunological
      castration in boars.

PMID- 20129745
TI  - Menopause, increased iron stores and cholesterol.

PMID- 20129746
TI  - Bone turnover markers and bone mineral density in hypertensive postmenopausal
      women on treatment.
AB  - OBJECTIVE: To evaluate bone mineral density (BMD) and bone metabolism in
      hypertensive postmenopausal women, and to differentiate the effect of thiazides
      from that of other antihypertensive agents. SUBJECTS AND METHODS: A community
      based population of 636 postmenopausal women, 293 with hypertension (160
      receiving thiazides, and 133 receiving other antihypertensive treatments), and
      343 control women, were evaluated. Serum levels of aminoterminal propeptide of
      type I collagen (P1NP), C-terminal telopeptide of type I collagen (beta-CTX), 25
      hydroxivitamin D, and intact parathyroid hormone were measured by
      electrochemiluminiscence. BMD was determined by DXA, and heel quantitative
      ultrasound measurements (QUS) with a gel-coupled device. RESULTS: BMD expressed
      as Z-score was higher in both groups of hypertensive women at all locations.
      Expressed as g/cm(2), it was also higher in patients on thiazides at femoral neck
      and lumbar spine. Only in the latter site, differences remained significant after
      adjusting for potential confounding variables, including BMI. Bone turnover
      markers were lower in both groups of hypertensive women, although the difference
      was greater in those on thiazides. After adjusting for potential confounders,
      differences remained significant only in the thiazide group. CONCLUSIONS: Our
      results add evidence to the idea that thiazides are beneficial to prevent bone
      loss.

PMID- 20129747
TI  - Hair analysis for Delta9-tetrahydrocannabinolic acid A--new insights into the
      mechanism of drug incorporation of cannabinoids into hair.
AB  - Differentiation between external contamination and incorporation of drugs or
      their metabolites from inside the body via blood, sweat or sebum is a general
      issue in hair analysis and of high concern when interpreting analytical results.
      In hair analysis for cannabinoids the most common target is Delta9
      tetrahydrocannabinol (THC), sometimes cannabidiol (CBD) and cannabinol (CBN) are
      determined additionally. After repeated external contamination by cannabis smoke
      these analytes are known to be found in hair even after performing multiple
      washing steps. A widely accepted strategy to unequivocally prove active cannabis
      consumption is the analysis of hair extracts for the oxidative metabolite 11-nor
      9-carboxy-THC (THC-COOH). Although the acidic nature of this metabolite suggests
      a lower rate of incorporation into the hair matrix compared to THC, it is not
      fully understood up to now why hair concentrations of THC-COOH are generally
      found to be much lower (mostly <10 pg/mg) than the corresponding THC
      concentrations. Delta9-Tetrahydrocannabinolic acid A (THCA A) is the preliminary
      end product of the THC biosynthesis in the cannabis plant. Unlike THC it is non
      psychoactive and can be regarded as a 'precursor' of THC being largely
      decarboxylated when heated or smoked. The presented work shows for the first time
      that THCA A is not only detectable in blood and urine of cannabis consumers but
      also in THC positive hair samples. A pilot experiment performed within this study
      showed that after oral intake of THCA A on a regular basis no relevant
      incorporation into hair occurred. It can be concluded that THCA A in hair almost
      exclusively derives from external contamination e.g. by side stream smoke.
      Elevated temperatures during the analytical procedure, particularly under
      alkaline conditions, can lead to decarboxylation of THCA A and accordingly
      increase THC concentrations in hair. Additionally, it has to be kept in mind that
      in hair samples tested positive for THCA A at least a part of the 'non-artefact'
      THC probably derives from external contamination as well, because in condensate
      of cannabis smoke both THC and THCA A are present in relevant amounts. External
      contamination by side stream smoke could therefore explain the great differences
      in THC and THC-COOH hair concentrations commonly found in cannabis users.

PMID- 20129748
TI  - Prefrontal brain function in children with anorexia nervosa: a near-infrared
      spectroscopy study.
AB  - To investigate the prefrontal hemodynamic response during a cognitive task in
      childhood anorexia nervosa (AN), we measured regional cerebral blood volume
      changes in terms of changes in hemoglobin concentrations [Hb], using near
      infrared spectroscopy (NIRS). Sixteen females with AN (mean age 14.2 years old)
      and 12 age-matched healthy female control subjects (mean age 14.3 years old)
      participated in this study. Waveform patterns for [Hb] during the word fluency
      task differed between the two groups, although their task performances showed no
      significant difference. In the control group, the [total-Hb] and [oxy-Hb]
      immediately increased and the [deoxy-Hb] immediately decreased after the
      beginning of the task and gradually reached the baseline level after the end of
      the task. The patients with AN were consistently characterized by an unchanged or
      less fluctuating response pattern of [total-Hb], [oxy-Hb] and [deoxy-Hb] during
      the task and rest periods. In the AN group, subjects with higher Eating Attitudes
      Test (EAT-26) scores showed higher [oxy-Hb] during the task. On the other hand,
      in the control group, subjects with higher EAT-26 scores showed lower [oxy-Hb]
      during the task. The grand waveforms of each [Hb] during a motor activation task,
      which was applied as a control task, did not differ significantly between two
      groups. The different prefrontal hemodynamic responses might indicate that AN
      subjects might apply fewer brain circuits or fewer neurons per circuit during
      cognitive tasks and might use different brain circuits in relation to their
      preoccupation with eating behaviors.

PMID- 20129749
TI  - Two novel missense mutations in the aspartoacylase gene in a Chinese patient with
      congenital Canavan disease.
AB  - We herein describe the first Chinese case of Canavan disease diagnosed by
      biochemical analysis and confirmed by DNA studies. We report two novel mutations:
      c.2T>C/M1T, an initiation codon mutation, and c.209A>G/N70S, which is located at
      the enzyme-substrate binding site. The combination of these two mutations
      resulted in a congenital form of Canavan disease.

PMID- 20129750
TI  - Off-resonance frequency filtered magnetic resonance imaging.
AB  - One of the main problems with rapid magnetic resonance imaging (MRI) techniques
      is the artifacts that result from off-resonance effects. The proposed off
      resonance frequency filtered MRI (OFF-MRI) method focuses on the elimination of
      off-resonance components from the image of the observed object. To maintain
      imaging speed and simultaneously achieve good frequency selectivity, MRI is
      divided into two steps: signal acquisition and post-processing. After the
      preliminary phase in which we determine imaging parameters, MRI takes place; the
      signal from the same object is successively acquired M times. As a result, we
      obtain M partial signals in k-space, from which we form the image of the observed
      object in the post-processing phase, after signal acquisition has been completed.
      This paper demonstrates that with proper selection of acquisition parameters and
      weighting coefficients in the post-processing phase, OFF-MRI is equivalent to
      filtering the signal by finite impulse response filter of length M. It is shown
      that with M successive acquisitions M-1 off-resonance components can be
      eliminated (filtered-out) from images, and therefore, only two acquisitions are
      needed to eliminate one off-resonance components. On the other hand, with OFF
      MRI, it is also possible to form the image of an arbitrary off-resonance
      component by eliminating all other off-resonance components, including the on
      resonance component. The proposed OFF-MRI method is suitable for MRI where rapid
      acquisition is required and elimination of off-resonance components can improve
      reliability of measurements.

PMID- 20129751
TI  - Elution behavior of insulin on high-performance size exclusion chromatography at
      neutral pH.
AB  - The pharmacopoeia protocol for HP-SEC of insulin, using an acidic non
      physiological eluent, does not represent insulin's association state in the
      formulation. This study aimed to evaluate insulin's elution behavior in HP-SEC in
      a "physiological" (aqueous, neutral pH) eluent, using on-line UV absorption and
      multi-angle laser light scattering detection. The effect of insulin concentration
      and association state in the formulation (monitored by circular dichroism) and
      eluent composition (zinc ion, arginine) on its elution behavior was assessed. We
      showed that the elution behavior of insulin in "physiological" HP-SEC is affected
      by both dynamic association-dissociation of insulin molecules and insulin-column
      interactions. Insulin molecules re-equilibrated in the HP-SEC eluent, making its
      elution behavior practically insensitive to the association state of insulin in
      the formulation. Zinc ions in the eluent promoted association of insulin to
      hexamers, whereas arginine overruled the effect of zinc ions and induced on
      column dissociation of insulin to dimers and monomers. Combined results from
      "physiological" and compendial HP-SEC were shown to provide a better view of the
      aggregation state of heat-stressed insulin than either of the single methods. The
      insights obtained with this study are crucial for a proper evaluation of HP-SEC
      data of insulin.

PMID- 20129752
TI  - Molecular spectroscopic studies on the interaction between ractopamine and bovine
      serum albumin.
AB  - To investigate the interaction between Ractopamine (RAC), an animal growth
      promoter, and bovine serum albumin (BSA), three spectroscopic approaches
      (fluorescence, UV-vis and FT-IR) and three different experiments (two mole-ratio
      and a Job's methods) were used to monitor the biological kinetic interaction
      procedure. The Stern-Volmer quenching constants K(SV), the binding constants
      K(a), and the number of binding sites n at 298, 301 and 304 K were evaluated by
      molecular spectroscopic approaches. The values of enthalpy (-13.47 kJ mol(-1))
      and entropy (78.39 J mol(-1)K(-1)) in the reaction indicated that RAC bound to
      BSA mainly by electrostatic and hydrophobic interaction. The site markers
      competitive experiments indicated that the binding of RAC to BSA primarily took
      place in site I. The spectra data matrix was further investigated with
      multivariate curve resolution-alternating least squares (MCR-ALS), and the
      concentration profiles and the pure spectra for three species (BSA, RAC and RAC
      BSA) existed in the kinetic interaction procedure, as well as the apparent
      equilibrium constants, were obtained.

PMID- 20129753
TI  - Effect of co-occurring disorders and intimate partner violence on substance abuse
      treatment outcomes.
AB  - This retrospective cohort study examined risk factors for co-occurring substance
      use and mental disorders (COD) and the effect of COD and intimate partner
      violence (IPV) victimization among women and IPV-related arrest among men on 1
      year substance abuse treatment outcomes. The study sample included clients
      admitted to Washington State publicly funded substance abuse treatment facilities
      in 2004-2007. COD was associated with a high substance use and IPV risk profile
      at admission. Having a COD decreased the odds of completing treatment by 30%
      among men and women and increased the risk of treatment reentry by 9% and 12%
      among men and women, respectively. IPV also decreased the odds of completing
      treatment among women and increased the risk of treatment reentry among men. Men
      with COD were less likely than those without COD to be arrested for substance
      related crimes but more likely to be arrested for violence-related crimes in the
      follow-up period. Implications of these findings are discussed.

PMID- 20129754
TI  - Nonmedical use of prescription stimulants and depressed mood among college
      students: frequency and routes of administration.
AB  - Studies demonstrate associations between nonmedical use of prescription
      stimulants (NMUPS) and depressed mood; however, relevance of NMUPS route of
      administration and frequency of use have not been examined. We hypothesized
      frequent NMUPS and nonoral routes would be significantly associated with
      depressed mood. A Web survey was self-administered by a probability sample of
      3,639 undergraduate students at a large U.S. university. The survey contained
      substance use (e.g., frequency, route of administration) and depressed mood
      measurement. Past-year prevalence of NMUPS was 6.0% (n = 212). Approximately 50%
      of frequent or nonoral NMUPS reported depressed mood. Adjusted odds of depressed
      mood were over two times greater among frequent monthly NMUPS (adjusted odds
      ratio [AOR] = 2.3, 95% confidence interval [CI] = 1.01-5.15) and nonoral routes
      of administration (AOR = 2.2, 95% CI = 1.36-3.70), after controlling for other
      variables. Nonmedical users of prescription stimulants should be screened for
      depressed mood, especially those who report frequent and nonoral routes of
      administration.

PMID- 20129755
TI  - Paraparesis after thoracic stent-graft relining for an unrecognized type III
      endoleak.
AB  - BACKGROUND: We examined the reasons for missing a type III endoleak on
      conventional imaging and the pathophysiology of paraparesis after relining this
      stent graft. METHODS AND RESULTS: A 46-year-old man was treated with a thoracic
      stent graft for thoracic rupture of a chronic type B thoracoabdominal dissection
      with aneurysm formation. In a second intervention, retrograde revascularization
      of the visceral and renal arteries was performed in combination with insertion of
      an abdominal stent graft. After initial shrinkage of the aneurysmal sac, the
      thoracic aortic diameter started increasing again. Consecutive three-phase
      helical computed tomographic scans did not reveal any endoleak. Because of
      unbearable back pain, an open surgical exploration was performed. This showed a
      type III endoleak. Relining of the thoracic stent graft was performed, but
      paraparesis developed. CONCLUSION: In patients with unexplained increase of the
      aneurysmal sac contrast-enhanced magnetic resonance imaging could help to
      illuminate the underlying endoleak. The collateral network concept can explain
      spinal cord injury by even minor hemodynamic changes.

PMID- 20129756
TI  - The effect of platelet-rich plasma on early and late bone healing using a mixture
      of particulate autogenous cancellous bone and Bio-Oss: an experimental study in
      goats.
AB  - Platelet-rich plasma (PRP), containing various growth factors, may speed up wound
      and bone healing. Using osteoconductive alloplastic materials in reconstructive
      surgery, the amount of autogenous bone needed can be reduced. The purpose of this
      experiment was to study the effect of PRP on a mixture of autogenous bone and
      deproteinized bovine bone mineral (Bio-Oss) particles in goats. Four, round,
      critical size defects were made in the foreheads of 20 goats. In all goats the
      defects were filled with a mixture of autogenous particulate cancellous bone and
      (Bio-Oss) particles, in which 1 ml of PRP was added in two of the four defects.
      The goats were allocated to four subgroups each containing five goats, which were
      killed after 1, 2, 6 and 12 weeks. The results of the histological and
      histomorphometric examination showed that early and late bone healing were not
      enhanced when PRP was used.

PMID- 20129757
TI  - Intraoral vertical ramus osteotomy: a simple method to prevent medial trapping of
      the proximal fragment.
AB  - Intraoral vertical ramus osteotomy (IVRO) is a useful surgical procedure for
      mandibular setback in patients with mandibular prognathism or mandibular
      asymmetry. IVRO has some intraoperative complications, such as the medial
      trapping of the proximal segment. Several techniques have been described to
      overcome this problem, but none can prevent it. This technical report describes a
      method that prevents the medial trapping of the proximal segment during IVRO.

PMID- 20129758
TI  - Vagus nerve stimulation for epilepsy activates the vocal folds maximally at
      therapeutic levels.
AB  - PURPOSE: Vagus nerve stimulation (VNS) for medically refractory epilepsy can give
      hoarseness due to stimulation of the recurrent laryngeal nerve. For a group of
      VNS-therapy users this side-effect interferes severely with their daily
      activities. Our goal was to investigate the severity of intra-operative VNS
      related vocal fold contraction at different pulse widths and current output
      parameters. We investigated electromyographic and morphometric alterations on the
      vocal folds during VNS. METHODS: Vocal fold EMG experiments were conducted intra
      operatively during the implantation of a VNS system. During surgery the VNS pulse
      generator was programmed to stimulate at different pulse durations. At each pulse
      width the EMG-threshold current was determined by electrical stimulation of the
      vagus nerve with increasing stimulation currents. Laryngostroboscopic examination
      was performed after surgery to analyze the effects of spontaneous stimulation on
      the larynx. RESULTS: The vocal fold EMG and morphodynamic changes in the larynx
      have been analyzed in eight patients. In all patients left vocal fold EMG
      threshold was between 0.25 and 0.50 mA. Pulse duration had little influence on
      the EMG-threshold level. Vocal fold EMG saturation levels were reached between
      0.75 and 1.00 mA. Video stroboscopic monitoring showed that stimulation induced
      an adductory spasm of either the ipsilateral vocal fold or the vestibular fold,
      and was present remarkably irrespective of the presence of hoarseness.
      CONCLUSIONS: VNS causes pronounced effects on the vocal folds even at low
      stimulation amplitudes. At therapeutic levels even at the lowest stimulation
      pulse durations, the vocal fold contract, however, this does not necessarily give
      hoarseness.

PMID- 20129759
TI  - Mozart K.448 and epileptiform discharges: effect of ratio of lower to higher
      harmonics.
AB  - PURPOSE: Certain music has been shown to improve mental function, leading to what
      is known as the Mozart effect. This study measured the impact of Mozart's Sonata
      for two pianos in D major, K.448, on different epileptic foci of epileptiform
      discharge in Taiwanese children (n=58) with seizure disorders and investigated
      the characteristics of the musical stimulus presented that resulted in
      epileptiform discharge reduction. METHODS: We examined the relationship between
      the number of discharges with the foci of epileptiform discharge (n=6), sleep
      state, gender, and mentality. A continuous electroencephalogram was recorded
      before, during and after exposure to Mozart's Sonata for two pianos in D major,
      K.448 (piano K.448), and the frequencies of discharges were compared. The study
      was repeated a week later using digitally computerized string version of the same
      musical stimulus (string K.448), in patients who responded to piano K.448 with
      the largest reduction in interictal discharges (n=11). RESULTS: Interictal
      discharges were reduced in most (81.0%) patients and varied greatly (33.10+/
      28.33%) as they listened to the piano K.448 (more fundamental tones and lower
      harmonics). Patients with generalized or central discharge showed the most
      improvement. In most patients (76.1%), the decrease in epileptiform discharges
      continued after the music ended. The state of wakefulness, gender and mentality
      did not affect the results. Although the string K.448 had a larger number of
      higher harmonics in the spectrogram analysis, the discharges were not reduced at
      all when listening to this music. CONCLUSION: These results suggest that
      listening to Mozart K.448 for two pianos reduced epileptiform discharges in
      children with epilepsy. This study suggests that it is possible to reduce the
      number of epileptiform discharges in some patients by optimizing the fundamental
      tones and minimizing the higher frequency harmonics.

PMID- 20129760
TI  - Diffusion tensor imaging identifies changes in normal-appearing white matter
      within the epileptogenic zone in tuberous sclerosis complex.
AB  - PURPOSE: To evaluate diffusion tensor imaging (DTI) indices of (i) cortical
      tubers and (ii) normal-appearing subcortical white matter adjacent to cortical
      tubers within the epileptogenic zone and non-epileptogenic zone. METHODS: Twelve
      children with tuberous sclerosis complex underwent MRI, DTI and
      magnetoencephalography (MEG). Regions of interest (ROIs) were placed within
      cortical tubers and normal-appearing subcortical white matter adjacent to
      cortical tubers within MEG identified epileptogenic zone and non-epileptogenic
      zone. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity
      (lambda(parallel)) and radial diffusivity (lambda(perpendicular)) were
      calculated. RESULTS: 26 out of 104 cortical tubers were in the epileptogenic
      zone. FA of cortical tubers in the epileptogenic zone was significantly lower
      than non-epileptogenic zone (p=0.015). There were no significant differences
      between MD (p=0.896), lambda(parallel) (p=0.672) and lambda(perpendicular)
      (p=0.651) of cortical tubers in the epileptogenic and non-epileptogenic zone. In
      normal-appearing subcortical white matter within the epileptogenic zone, FA was
      lower (p=0.001) and lambda(perpendicular) (p=0.011) was higher than non
      epileptogenic zone. There were no significant differences between MD (p=0.110)
      and lambda(parallel) (p=0.735) of normal-appearing subcortical white matter
      within the epileptogenic and non-epileptogenic zone. CONCLUSION: DTI changes in
      normal-appearing white matter within the epileptogenic zone could represent
      abnormal white matter related to MRI-occult dysplastic cortex or ictal/interictal
      activity.

PMID- 20129761
TI  - An integrated fMRI, SEPs and MEPs approach for assessing functional organization
      in the malformed sensorimotor cortex.
AB  - PURPOSE: Malformations of cortical development are often accompanied by an
      abnormal cortical pattern. Due to its propensity to involve discrete cortical
      areas, polymicrogyria represents an interesting model for assessing the
      reorganization of cortical function in relation to the disrupted anatomy.
      Functional MRI, TMS and SEPs can provide a highly complementary, multimodal
      approach to map noninvasively the functional rearrangement of sensorimotor
      functions in the polymicrogyric cortex, and to obtain a coherent modelling. We
      report here an illustrative case which is included in a patients series under
      study using a block design 3T fMRI, short-latency SEPs as identified on the basis
      of their latency, polarity, and scalp distribution and an assessment of the area
      and volume of the motor maps and the relative position of the center of gravity
      and hot spot. RESULTS: A 15 years old girl, with drug-resistant epilepsy and left
      perisylvian polymicrogyria that was part of a large epileptogenic network
      including also the mesial aspect of the left frontal lobe, exhibited a normal
      distribution of somatomotor responses in the expected anatomic sites, with a
      dissociation between motor functions, which were slightly impaired in the
      malformed hemisphere, and bilaterally normal sensory responses. In this patient,
      a large resection of epileptogenic zone, sparing eloquent areas as previously
      identified, should be planned in order to improve seizure outcome. CONCLUSIONS:
      An integrated fMRI, TMS and SEP mapping approach helps defining the relationship
      between epileptogenic zones and somatomotor areas. Studies of greater number of
      patients will be necessary in order to identify the general rules that determine
      the functional representation in the malformed cortex.

PMID- 20129762
TI  - Synthetic antimicrobial peptide L8 (MHLHKTSRVTLYLL) has membrane permeabilisation
      and bacterial aggregation activity.

PMID- 20129763
TI  - Efficacy of voriconazole in a murine model of invasive paecilomycosis.
AB  - We studied the efficacy of voriconazole (VRC) and amphotericin B (AMB) in an
      immunosuppressed murine model of disseminated infection by two strains of
      Paecilomyces lilacinus. Mice were treated with VRC 60 mg/kg/day orally or AMB
      3mg/kg/day intraperitoneally, beginning 1 day after infection and continuing for
      9 days. To avoid rapid clearance of VRC, animals receiving VRC and the control
      group were given grapefruit juice instead of water. VRC significantly prolonged
      survival with respect to the group treated with AMB and the control group for
      both strains (P=0.005 and P<0.0001, respectively, for strain FMR 5522; and
      P=0.0002 and P<0.0001, respectively, for strain FMR 8252). VRC reduced the fungal
      load in the spleen, kidneys and liver of infected mice for both strains tested.
      Survival of mice challenged with strain FMR 8252 treated with AMB did not differ
      from that of the control group (P=0.223), being worse than that of the mice
      treated with VRC (P=0.0002). AMB was not able to reduce the tissue burden in any
      organ with respect to the control group for both strains studied.

PMID- 20129764
TI  - Mapping the brain pathways of traumatic memory: inactivation of protein kinase M
      zeta in different brain regions disrupts traumatic memory processes and
      attenuates traumatic stress responses in rats.
AB  - BACKGROUND: Protein kinase M zeta (PKMzeta), a constitutively active isoform of
      protein kinase C, has been implicated in protein synthesis-dependent maintenance
      of long-term potentiation and memory storage in the brain. Recent studies
      reported that local application of ZIP, a membrane-permeant PKMzeta inhibitor,
      into the insular cortex (IC) of behaving rats abolished long-term memory of taste
      associations. METHOD: This study assessed the long-term effects of local
      applications of ZIP microinjected immediately (1 h) or 10 days after predator
      scent stress exposure, in a controlled prospectively designed animal model for
      PTSD. Four brain structures known to be involved in memory processes and in
      anxiety were investigated: lateral ventricle (LV), dorsal hippocampus (DH),
      basolateral amygdala and IC. The outcome measures included behavior in an
      elevated plus maze and acoustic startle response 7 days after microinjection, and
      freezing behavior upon exposure to trauma-related cue 8 days after
      microinjection. Previously acquired/encoded memories associated with the IC were
      also assessed. RESULTS: Inactivation of PKMzeta in the LV or DH within 1h of
      exposure effectively reduced PTSD-like behavioral disruption and trauma cue
      response 8 days later. Inactivation of PKMzeta 10 days after exposure had
      equivalent effects only when administered in the IC. The effect was demonstrated
      to be specific for trauma memories, whereas previously acquired data were
      unaffected by the procedure. CONCLUSION: Predator scent related memories are
      located in different brain areas at different times beginning with an initial
      hippocampus-dependent consolidation process, and are eventually stored in the IC.
      These bring the IC to the forefront as a potential region of significance in
      processes related to traumatic stress-induced disorders.

PMID- 20129765
TI  - Identification of Vibrio harveyi as a causative bacterium for a tail rot disease
      of sea bream Sparus aurata from research hatchery in Malta.
AB  - A bacterial disease was reported from gilthead sea bream (Sparus aurata) within a
      hatchery environment in Malta. Symptoms included complete erosion of tail,
      infection in the eye, mucous secretion and frequent mortality. A total of 540
      strains were initially isolated in marine agar from different infected body parts
      and culture water sources. Subsequently 100 isolates were randomly selected,
      identified biochemically and all were found to be Vibrio harveyi-related
      organisms; finally from 100 isolates a total of 13 numbers were randomly selected
      and accurately identified as V. harveyi by 16S rRNA gene sequencing and species
      specific PCR. Ribotyping of these strains with HindIII revealed total of six
      clusters. In vivo challenge study with representative isolates from each cluster
      proved two clusters each were highly pathogenic, moderately pathogenic and non
      pathogenic. All 13 isolates were positive for hemolysin gene, a potential
      virulence factor. Further analysis revealed probably a single copy of this gene
      was encoded in all isolates, although not in the same locus in the genome.
      Although V. harveyi was reported to be an important pathogen for many aquatic
      organisms, to our knowledge this might be the first report of disease caused by
      V. harveyi and their systematic study in the sea bream hatchery from Malta.

PMID- 20129766
TI  - Effect of purified saponin mixture from Astragalus corniculatus on enzyme- and
      non-enzyme-induced lipid peroxidation in liver microsomes from spontaneously
      hypertensive rats and normotensive rats.
AB  - The aim of the following study was to evaluate the effect of a purified saponin
      mixture (PSM), isolated from Astragalus corniculatus Bieb. (Fabaceae), on enzyme
      induced and non-enzyme-induced lipid peroxidation (LPO), in liver microsomes from
      spontaneously hypertensive rats (SHRs) - strain Okamoto Aoki, as compared to
      normotensive Wistar rats (NTRs). The enzyme-induced lipid peroxidation was
      performed by incubating rat liver microsomes with carbonetetrachloride (CCl(4))
      in the presence of NADPH. In nonenzyme-induced LPO, the microsomes were incubated
      with a solution of iron sulphate and ascorbinic acid (Fe(2+)/AA). The effect of
      PSM (196.5 microg/ml) was assessed at 20 minutes' incubation time. MDA, a product
      of LPO, was measured spectrophotometrically. The results of our study showed that
      the initial MDA quantity in SHRs was significantly higher, than in NTRs. The
      incubation of the microsomes from both strains with PSM (196.5 microg/ml),
      resulted in significant reduction of MDA level, by 25% in SHRs. In NTRs, the
      formation of MDA was unchanged. In enzyme-induced LPO model, PSM significantly
      decreased the formation of MDA, by 55% in NTRs and by 35% in SHRs, compared to
      the respective control groups. In the model of non-enzyme induced LPO, PSM
      significantly decreased the formation of MDA by 95% in NTRs and practically
      restored it to the control level. The MDA quantity in SHR's microsomes was
      reduced by 25%. According to the results of this experiment we could conclude
      that PSM, isolated from Astragalus corniculatus, shows antioxidant activity both
      in SHRs and NTRs and the effect in NTRs is more pronounced.

PMID- 20129767
TI  - Bronchitis-like symptoms and proximity air pollution in French elderly.
AB  - BACKGROUND: Our aim was to explore the association between respiratory health and
      proximity air quality in elderly. METHODS: The prevalence of respiratory
      conditions was linked in 2104 individuals aged > or =65 years recruited in
      Bordeaux (3C Study) to home address concentrations of NO2, CO, SO2, fine
      particles (PM(10)), VOCs and benzene, estimated through a dispersion model
      combining data on background air pollution, traffic characteristics, and
      conditions of topographical and meteorological dispersion of air pollutants.
      RESULTS: Mean [minimum; maximum] values of the annual concentrations
      (microg/m(3)) of proximity air pollutants were respectively: 28 [18; 72.2] for
      NO2, 420 [350; 1337] for CO, 7.5[5; 13.7] for SO2, 23.1 [19; 51] for PM(10), 8.1
      [0.01; 116.6] for VOCs and 1.8 [1.5; 6.9] for benzene. Using a binary logistic
      regression model, PM(10) were significantly associated with usual cough (Odds
      Ratio=1.33 (95% confidence interval: 1.00-1.77) for exposed compared to non
      exposed) and SO(2) with usual cough (1.55 (1.16-2.08)) and phlegm (1.45 (1.04
      2.01)). We found a 10% and a 23% increase in usual cough for a 10microg/m(3)
      increment in PM(10) and a 1microg/m(3) increment in SO2 respectively, and a 23%
      increase in usual phlegm for a 1microg/m(3) increase in SO2. A sensitivity
      analysis showed similar results when considering 3-year proximity pollution. A
      more pronounced effect of SO2 and PM(10) on usual cough and phlegm was observed
      in woman. CONCLUSIONS: Our assessment of exposure to proximity air pollution has
      shown an increased prevalence of bronchitis-like symptoms in elderly living in
      areas polluted by SO2 and PM(10).

PMID- 20129768
TI  - HSP47 in lung fibroblasts is a predictor of survival in fibrotic nonspecific
      interstitial pneumonia.
AB  - BACKGROUND: The histopathologic pattern is currently the most important
      prognostic marker for idiopathic interstitial pneumonia (IIP). However, more
      highly sensitive markers are now required. Heat shock protein (HSP) 47, a
      collagen-specific molecular chaperone, is involved in the processing and/or
      secretion of procollagens, and it has been demonstrated that HSP47 expression is
      significantly higher in the lung specimens of idiopathic UIP than in UIP
      associated with collagen vascular diseases (CVD). However, its expression in
      nonspecific interstitial pneumonia (NSIP), the other common pathological pattern
      of IIP, has not been well investigated. Therefore, the association between lung
      fibroblast HSP47 expression and prognosis in fibrotic NSIP was evaluated.
      METHODS: Surgical lung biopsy specimens of 63 patients [idiopathic fibrotic
      NSIP=19, fibrotic NSIP associated with CVD=9, idiopathic UIP=26, and UIP
      associated with CVD=9] were reviewed, and a score for lung fibroblast HSP47
      expression was assigned. These patients' clinical features and survival were also
      analyzed. RESULTS: There was no significant difference in HSP47 expression
      between idiopathic fibrotic NSIP and fibrotic NSIP associated with CVD. The
      idiopathic fibrotic NSIP patients with higher HSP47 expression levels in their
      lung specimens had a poorer prognosis than patients with lower HSP47 expression
      levels. CONCLUSIONS: The present results suggest that lung fibroblast HSP47
      expression may be a useful new prognostic marker for idiopathic fibrotic
      nonspecific interstitial pneumonia.

PMID- 20129769
TI  - Two variants of occupational asthma separable by exhaled breath nitric oxide
      level.
AB  - Exhaled nitric oxide (FE(NO)) has been used as a marker of asthmatic inflammation
      in non-occupational asthma, but some asthmatics have a normal FE(NO). In this
      study we investigated whether, normal FE(NO) variants have less reactivity in
      methacholine challenge and smaller peak expiratory flow (PEF) responses than high
      FE(NO) variants in a group of occupational asthmatics. METHODS: We measured
      FE(NO) and PD(20) in methacholine challenge in 60 workers currently exposed to
      occupational agents, who were referred consecutively to a specialist occupational
      lung disease clinic and whose serial PEF records confirmed occupational asthma.
      Bronchial responsiveness (PD(20) in methacholine challenge) and the degree of PEF
      change to occupational exposures, (measured by calculating diurnal variation and
      the area between curves score of the serial PEF record in Oasys), were compared
      between those with normal and raised FE(NO). Potential confounding factors such
      as smoking, atopy and inhaled corticosteroid use were adjusted for. RESULTS:
      There was a significant correlation between FE(NO) and bronchial hyper
      responsiveness in methacholine challenge (p = 0.011), after controlling for
      confounders. Reactivity to methacholine was significantly lower in the normal
      FE(NO) group compared to the raised FE(NO) group (p = 0.035). The two FE(NO)
      variants did not differ significantly according to the causal agent, the
      magnitude of the response in PEF to the asthmagen at work, or diurnal variation.
      CONCLUSIONS: Occupational asthma patients present as two different variants based
      on FE(NO). The group with normal FE(NO) have less reactivity in methacholine
      challenge, while the PEF changes in relation to work are similar.

PMID- 20129770
TI  - Nanomaterial-assisted aptamers for optical sensing.
AB  - Aptamers are single-strand DNA or RNA selected in vitro that bind specifically
      with a broad range of targets from metal ions, organic molecules, to proteins,
      cells and microorganisms. As an emerging class of recognition elements, aptamers
      offer remarkable convenience in the design and modification of their structures,
      which has motivated them to generate a great variety of aptamer sensors
      (aptasensors) that exhibit high sensitivity as well as specificity. On the other
      hand, the development of nanoscience and nanotechnology has generated
      nanomaterials with novel properties compared with their counterparts in
      macroscale. By integrating their strengths of both fields, recently, versatile
      aptamers coupling with novel nanomaterials for designing nanomaterial-assisted
      aptasensors (NAAs) make the combinations universal strategies for sensitive
      optical sensing. NAAs have been considered as an excellent sensing platform and
      found wide applications in analytical community. In this review, we summarize
      recent advances in the development of various optical NAAs, employing various
      detection techniques including colorimetry, fluorometry, surface-enhanced Raman
      scattering (SERS), magnetic resonance imaging (MRI) and surface plasmon resonance
      (SPR).

PMID- 20129771
TI  - Competitive multi-immunosensing of pesticides based on the particle manipulation
      with negative dielectrophoresis.
AB  - In this work, we have applied particle manipulation based on negative
      dielectrophoresis (n-DEP) to develop rapid and separation-free immunosensing
      systems. Two widely used pesticides, atrazine and bromopropylate, were used as
      target molecules to demonstrate competitive immunosensing based on the rapid
      manipulation of microparticles. A suspension of the fluorescence microparticles
      modified with a specific antibody was injected into the n-DEP device consisting
      of the interdigitated microarray (IDA) electrode and indium-tin-oxide (ITO)
      substrate immobilized by protein conjugation with antigen. The application of 2
      MHz AC voltage (16 V peak-to-peak) to the IDA forced most of the particles to
      form a line pattern on the upper ITO over the gaps of IDA within 60s. In the
      absence of analytes, patterned microparticles were irreversibly captured on the
      ITO by the construction of immuno-complexes. When the microparticles bearing anti
      atrazine IgG antibody were suspended in an analyte (atrazine) solution,
      irreversible capturing of microparticles on the ITO was inhibited because of the
      occupation of the binding sites of the antibodies with free-atrazine. As a
      result, the analyte molecules were re-dispersed from the ITO to disintegrate the
      line formation after turning off the voltage. We could discriminatively detect
      the fluorescence intensity of the captured microparticles at the designated areas
      from that of the uncaptured microparticles suspended in the solution. Thus, the
      separation steps usually required for conventional immunoassay are eliminated in
      the present procedure. A pre-incubation of microparticles for 3 min in an orange
      juice solution containing analyte allowed for the determination of the atrazine
      and bromopropylate concentrations with a limit of detection of 4 and 1.5 microg
      L(-1), respectively, providing sufficient detectability to achieve international
      regulations regarding pesticide residues in food samples. The assay was
      significantly accelerated by the rapid particle manipulation with n-DEP and
      totally accomplished within 5 min. We also demonstrated the possibility of the
      simultaneous determination of two pesticide residues by using the DEP devices
      with two channels modified with specific competitors for atrazine and
      bromopropylate.

PMID- 20129772
TI  - Nanostructured poly(3,4-ethylenedioxythiophene)-metalloporphyrin films: improved
      catalytic detection of peroxynitrite.
AB  - We investigated in this paper the sensing performance of inherently conductive
      polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), functionalized with hemin
      (iron protoporphyrin) as an electrocatalytic reporter. The sensing platform is
      prepared by electrodeposition of a composite film of hemin-PEDOT on a 30-microm
      diameter carbon fiber electrode (CFE). The polymerized films were characterized
      by field emission scanning electron microscopy (FESEM), which pointed to
      nanostructured films with tortuous pores. The electrocatalytic oxidation of
      peroxynitrite was characterized by cyclic voltammetry as well as other
      electrochemical methods. The catalytic current is proportional to the analyte's
      concentration. Optimized hemin-PEDOT modified CFEs were utilized for the first
      time to detect ONO2(-), with a response time down to 5 s and a limit of detection
      as low as 200 nM as evidenced by amperometry. Our hemin-PEDOT modified CFEs have
      a sensitivity of 13 nA/microM, ca.130 times higher than the bare CFE. More work
      is underway using other metalloporphyrins as electrocalalysts to improve the
      detection limit, the selectivity, and to further miniaturize these hemin-PEDOT
      modified electrodes.

PMID- 20129773
TI  - Aligned carbon nanotubes on quartz substrate for liquid gated biosensing.
AB  - A facile and high performance biosensing platform using aligned carbon nanotubes
      on quartz substrate is reported in this communication. Single walled carbon
      nanotubes are grown on quartz substrates by a chemical vapor deposition process
      and are characterized with field emission scanning electron microscopy and atomic
      force microscopy in order to verify the quality of the material. The quartz
      substrate is then directly used as a biosensor in a field effect transistor
      configuration. In order to demonstrate the sensing capabilities of the fabricated
      sensor devices, electronic detection of prostate specific antigen, a potential
      cancer biomarker, is carried out by adopting liquid gated configuration. A
      conductivity change due to the specific binding of target antigen with the
      immobilized receptor antibody demonstrates the sensing capabilities of the
      fabricated device. Sub-nM detection sensitivities have been obtained using the
      adopted direct immunoassay approach, which shows that the device responds to
      clinically relevant concentration regimes.

PMID- 20129774
TI  - Label-free colorimetric detection of picomolar thrombin in blood plasma using a
      gold nanoparticle-based assay.
AB  - We unveil a novel, label-free, colorimetric assay--using fibrinogen (Fib) and
      gold nanoparticles (Au NPs)--for the highly selective and sensitive detection of
      thrombin. Addition of fibrinogen to a solution of Au NPs (average diameter: 56
      nm) led to ready conjugation, forming Fib-Au NPs through electrostatic and
      hydrophobic interactions. Introduction of thrombin (a serine protease) into the
      Fib-Au NPs solutions in the presence of excess fibrinogen induced the formation
      of insoluble fibrillar fibrin-Au NPs agglutinates through the polymerization of
      the unconjugated and conjugated fibrinogen. After centrifugation, the absorbance
      at 532 nm of the supernatants decreased upon increasing the concentration of
      thrombin. This Fib-Au NP probe provides high sensitivity [limit of detection
      (LOD): 0.04 pM] for thrombin, with remarkable selectivity over other proteins and
      proteases. The range of linearity for the absorbance against the thrombin
      concentration was 0.1-10 pM (R(2)=0.96). This approach provides an LOD for
      thrombin that is lower than those obtainable using other nanomaterial- and
      aptamer-based detection methods. We validated the utility of this Fib-Au NP probe
      through separate analyses of thrombin and Factor Xa at picomolar levels in plasma
      samples--without the need for sample pretreatment. This technique appears to have
      practical potential in the diagnosis of diseases associated with coagulation
      abnormalities and cancers (e.g., pulmonary metastasis).

PMID- 20129775
TI  - Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K
      superfamily and human cancer cell line panel JFCR39.
AB  - As accumulating evidences suggest close involvement of phosphatidylinositol 3
      kinase (PI3K) in various diseases particularly cancer, considerable competition
      occurs in development of PI3K inhibitors. Consequently, novel PI3K inhibitors
      such as ZSTK474, GDC-0941 and NVP-BEZ235 have been developed. Even though all
      these inhibitors were reported to inhibit class I PI3K but not dozens of protein
      kinases, whether they have different molecular targets remained unknown. To
      investigate such molecular target specificity, we have determined the inhibitory
      effects of these novel inhibitors together with classical PI3K inhibitor LY294002
      on PI3K superfamily (including classes I, II, and III PI3Ks, PI4K and PI3K
      related kinases) by using several novel non-radioactive biochemical assays. As a
      result, ZSTK474 and GDC-0941 indicated highly similar inhibition profiles for
      PI3K superfamily, with class I PI3K specificity much higher than NVP-BEZ235 and
      LY294002. We further investigated their growth inhibition effects on JFCR39, a
      human cancer cell line panel which we established for molecular target
      identification, and analysed their cell growth inhibition profiles (fingerprints)
      by using COMPARE analysis programme. Interestingly, we found ZSTK474 exhibited a
      highly similar fingerprint with GDC-0941 (r=0.863), more similar than with that
      of either NVP-BEZ235 or LY294002, suggesting that ZSTK474 shares more in
      molecular targets with GDC-0941 than with either of the other two PI3K
      inhibitors, consistent with the biochemical assay result. The biological
      implication of the difference in molecular target specificity of these PI3K
      inhibitors is under investigation.

PMID- 20129776
TI  - Application of 2-factorial design on the enhanced production of calcium gluconate
      by a mutant strain of Aspergillus niger.
AB  - Sixty-eight isolates of the filamentous fungus Aspergillus niger were examined
      for calcium gluconate production under submerged culture conditions in 500-ml
      Erlenmeyer flasks. The isolate Chem-15 was selected for improvement through
      ultraviolet (UV) light-induced mutagenesis. Among viable mutants, strain 32
      exhibited the best gluconate productivity, and it was subjected to N-methyl N
      nitro N-nitroso guanidine (NG) treatment. Mutant strain NG-7 gave the highest
      gluconate production (86.48g/L) which varied significantly (p0.05) from that of
      the wild type. The mutant was cultured overnight and plated on 5-fluorocytosine
      PDA medium. Gluconate productivity was increased by 35% when the process
      parameters, incubation period (72h), initial pH (6.5), glucose as carbon source
      (15%), inoculum size (1.875x10(6)CFU/ml) and corn steep liquor (CSL) as nitrogen
      source (0.5%) were optimized using a 2-factorial Plackett-Burman design. Maximal
      glucose oxidase activity (28U/ml/min) was achieved at the optimal fermentation
      conditions with 26.5g/L DCM. The model terms were highly significant thus
      suggesting the potential commercial utility of the mutant (HS, df=3 approximately
      0.0182).

PMID- 20129777
TI  - Biorefinery approach for coconut oil valorisation: a statistical study.
AB  - The biorefinery approach, consisting in transesterification using methanol and
      potassium hydroxide as catalyst, has been used to assess coconut oil
      valorisation. Due to the fatty acid composition of coconut oil, low (LMWME) and
      high (HMWME) molecular weight fatty acid methyl esters were obtained. Methyl
      laurate (78.30 wt.%) is the major component of the low molecular weight fraction.
      The influence of variables such as temperature and catalyst concentration on the
      production of both fractions has been studied and optimized by means of factorial
      design and response surface methodology (RSM). Two separate optimum conditions
      were found to be a catalyst concentration of 0.9% and 1% and an operation
      temperature of 42.5 degrees C and 57 degrees C for LMWME and HMWME, respectively,
      obtaining conversion rates of 77.54% and 25.41%. The valuable components of LMWME
      may be recovered for sale as biolubricants or biosolvents, the remaining fraction
      could be used as biodiesel, matching the corresponding European Standard.

PMID- 20129778
TI  - A new type of chitosan hydrogel sorbent generated by anionic surfactant gelation.
AB  - A new type of chitosan hydrogel beads (CSB) with a core-shell membrane structure
      was generated by sodium dodecyl sulfate (SDS) gelation process. CSB exhibited
      higher mechanical strength and acid stability than chitosan hydrogel beads (CB)
      formed by alkali gelation. The effect of SDS concentration variation during
      gelation on the adsorption capacity of CSB for congo red (CR) as a model anionic
      dye showed that CSB formed by 4gl(-1) SDS gelation had the highest adsorption
      capacity. The maximum adsorption capacity of CSB (208.3mgg(-1)) obtained from the
      Sips model was found slightly higher than that of CB (200.0mgg(-1)). Membrane
      materials of CSB obtained after squeezing core water from the beads showed
      approximately 25 times higher volumetric adsorption capacity than CB.

PMID- 20129779
TI  - Effects of EDTA on phytoextraction of heavy metals (Zn, Mn and Pb) from sludge
      amended soil with Brassica napus.
AB  - Sludge application is a reliable practice to ameliorate soil fertility. However,
      repetitive sludge addition represents a potential soil contamination source with
      heavy metals, which must be extracted. The aim of this study was to evaluate the
      capacity of Brassica napus to remove metals from soils amended with sludge, and
      to study the effect of EDTA on this process. Seedlings were cultivated in
      presence of sludge combined or not with EDTA. Results showed that sludge
      ameliorate significantly biomass production. This effect was accompanied with an
      increase in Pb, Zn and Mn shoot concentrations. EDTA application does not affect
      significantly plant growth. However, this chelator enhances shoot metals
      accumulation. It's therefore concluded that sludge has a beneficial effect on
      soil fertility, B. napus can be used for the decontamination of affected soils
      and that the EDTA addition increases the ability of B. napus to accumulate heavy
      metals.

PMID- 20129780
TI  - Microbial population dynamics during startup of a full-scale anaerobic digester
      treating industrial food waste in Kyoto eco-energy project.
AB  - The microbial community in a full-scale anaerobic digester (2300m3) treating
      industrial food waste in the Kyoto Eco-Energy Project was analyzed using terminal
      restriction fragment length polymorphism for eubacterial and archaeal 16S rRNA
      genes. Both thermophilic and mesophilic sludge of treated swine waste were seeded
      to the digestion tank. During the 150-day startup period, coffee grounds as a
      main food waste, along with potato, kelp and boiled beans, tofu, bean curd lees,
      and deep-fried bean curd were fed to the digestion process step-by-step (max.
      40t/d). Finally, the methane yield reached 360m3/t-feed with 40days' retention
      time, although temporary accumulation of propionate was observed. Eubacterial
      communities that formed in the thermophilic digestion tank differed greatly from
      both thermophilic and mesophilic types of seed sludge. Results suggest that the
      Actinomyces/Thermomonospora and Ralstonia/Shewanella were contributors for
      hydrolyzation and degradation of food waste into volatile fatty acids. Acetate
      utilizing methanogens, Methanosaeta, were dominant in seed sludges of both types,
      but they decreased drastically during processing in the digestion tank.
      Methanosarcina and Methanobrevibacter/Methanobacterium were, respectively,
      possible main contributors for methane production from acetate and H2 plus CO2.

PMID- 20129781
TI  - Use of polystyrene-supported 2-isobutoxy-1-isobutoxycarbonyl-1,2-dihydroquinoline
      for the preparation of a hapten-protein conjugate for antibody development.
AB  - Polystyrene-supported 2-isobutoxy-1-isobutoxycarbonyl-1,2-dihydroquinoline (PS
      IIDQ), a polymer-supported covalent coupling reagent, was successfully employed
      for the first time in the bioconjugation of an example hapten (phytanic acid
      derivative) to a carrier protein (bovine serum albumin (BSA)) within the context
      of immunogen preparation for antibody development. The ability of the prepared
      example phytanic acid derivative-BSA conjugate to bind an anti-phytanic acid
      antibody was confirmed using an enzyme-linked immunosorbent assay (ELISA).

PMID- 20129782
TI  - Carbonic anhydrase activators: Activation of the beta-carbonic anhydrase from the
      pathogenic yeast Candida glabrata with amines and amino acids.
AB  - The protein encoded by the NCE103 gene of Candida glabrata, a beta-carbonic
      anhydrase (CA, EC 4.2.1.1) designated as CgCA, was investigated for its
      activation with amines and amino acids. CgCA was weakly activated by amino acids
      such as l-/d-His, l-Phe, l-DOPA, and l-Trp and by histamine or dopamine (K(A)s of
      21.2-37microM) but more effectively activated by d-Phe, d-DOPA, d-Trp as well as
      serotonin, pyridyl-alkylamines, aminoethyl-piperazine/morpholine (K(A)s of 10.1
      16.7microM). The best activators were l-/d-Tyr, with activation constants of 7.1
      9.5microM. This study may bring a better understanding of the
      catalytic/activation mechanisms of beta-CAs from pathogenic fungi.

PMID- 20129783
TI  - Podophyllotoxin analogues active versus Trypanosoma brucei.
AB  - In an effort to discover novel anti-trypanosomal compounds, a series of
      podophyllotoxin analogues coupled to non-steroidal anti-inflammatory drugs
      (NSAIDs) has been synthesized and evaluated for activity versus Trypanosoma
      brucei and a panel of human cell lines, revealing compounds with low nano-molar
      potencies. It was discovered that coupling of NSAIDs to podophyllotoxin increased
      the potencies of both compounds over 1300-fold. The compounds were shown to be
      cytostatic in nature and seem to act via de-polymerization of tubulin in a manner
      consistent with the known activities of podophyllotoxin. The potencies against T.
      brucei correlated directly with LogP values of the compounds, suggesting that the
      conjugates are acting as hydrophobic tags allowing podophyllotoxin to enter the
      cell.

PMID- 20129784
TI  - Cytosol as battleground: ubiquitin as a weapon for both host and pathogen.
AB  - Ubiquitin was first described as a tag allowing cells to degrade and recycle
      their own proteins. Recent research has shown ubiquitin to be central for immune
      system recognition of invading bacteria. This review describes a set of complex
      host-pathogen interactions that are dependent on ubiquitination. From the host
      perspective, ubiquitin-dependent activation of inflammation and degradation of
      bacterial effectors is protective. Several pathogens become ubiquitinated in the
      host cell cytosol, and recent research suggests that this could trigger a form of
      autophagy, increasingly recognized as an important mechanism for the control of
      infection by a variety of human pathogens. Meanwhile, bacteria have developed
      mechanisms to evade or exploit the fundamental processes activated by
      ubiquitination, producing both ubiquitin ligases and deubiquitinases that
      modulate host responses.

PMID- 20129785
TI  - Determination of preferred walking speed on treadmill may lead to high oxygen
      cost on treadmill walking.
AB  - The energy consumption of walking relates to the intensity of physical effort and
      can be affected by the alterations in walking speed. Therefore, walking speed can
      be accepted as a crucial, determinant of energy consumption measurement for a
      walking test. We aimed to investigate the differences in preferred walking speed
      (PWS) determined both on overground and on a treadmill and, to measure walking
      energy expenditure and spatio-temporal parameters of gait on a treadmill at both,
      speeds. Participants (n=26) walked on a treadmill at two pre-determined speeds
      for 7 min while, indirect calorimetry measurements were being performed. Spatio
      temporal parameters were collected, by video-taping during each walking session
      on a treadmill. The average overground preferred walking speed (O-PWS) was
      85.96+/-12.82 m/min and the average treadmill preferred walking speed (T-PWS),
      was 71.15+/-13.85 m/min. Although T-PWS was lower, oxygen cost was statistically
      higher when, treadmill walking at T-PWS (0.158+/-0.02 ml/kg/m) than when the
      treadmill walking at O-PWS, (0.1480+/-0.02 ml/kg/m). Cadence (127+/-9.13
      steps/min), stride (134.02+/-14.09 cm) and step length (67.02+/-6.90 cm) on the
      treadmill walking at O-PWS were significantly higher than cadence (119+/-10
      steps/min), stride (117.96+/-14.38 cm) and step length (59.13+/-7.02 cm) on the
      treadmill walking at TPWS. In conclusion, walking on treadmill using O-PWS is
      more efficient than walking on treadmill using TPWS, in walking tests. Since
      using T-PWS for treadmill walking tests overestimates the oxygen cost of walking,
      O-PWS should be used for oxygen consumption measurement during treadmill walking
      tests.

PMID- 20129786
TI  - Measures of frontal plane stability during treadmill and overground walking.
AB  - Given the consequences of falling to the side by older adults, attention has
      focused on identifying variables associated with changes in lateral stability and
      fall risk. Step-width (SW) and step-width variability (SWV) have traditionally
      been associated with such changes. Recently the "margin of stability" (MOS) has
      been adopted for describing dynamic stability. Although these measures may be
      influenced by the conditions during which locomotion occurs, only one published
      within-subject study has compared SW (but not SWV or MOS) during overground and
      treadmill walking. Therefore, we compared SW, SWV and minimum MOS (MOS(min)) in
      10 healthy young subjects walking at self-selected speeds, both overground and on
      a treadmill. We found SW was significantly larger (p=0.001), and SWV
      significantly smaller (p=0.001) during treadmill walking, and that these changes
      were meaningfully correlated between tasks. In contrast, MOS(min) was insensitive
      to treadmill versus overground walking. This suggested first, that SW and SWV
      only partially reflect frontal plane stability, and second, that the goal of the
      central nervous system may be to maintain a constant MOS(min) regardless of task.

PMID- 20129787
TI  - Non-linear analysis of the structure of variability in midfoot kinematics.
AB  - INTRODUCTION: Evaluation of structural variability in biological time series
      through measures such as sample entropy (SaEn) has provided important information
      in neurology and cardiology. This has contributed to the development of the "loss
      of complexity hypothesis" where high variability has been described as healthy
      flexibility and low variability associated with pathology. The purpose of this
      study was to calculate sample entropy (SaEn) to establish normal values of non
      linear variability and to examine which factors are associated with SaEn in
      midfoot kinematics. METHOD: Static foot posture was measured using Foot Posture
      Index. A video sequence analysis system was used to quantify midfoot kinematics
      during walking in the sagittal plane. SaEn was calculated for navicular drop
      during stand phase as an expression of the dynamic complexity. RESULTS: A
      significant difference was observed between the three major foot types and
      between genders (p<0.001). Mean SaEn in women were 1.10+/-0.19 (supinated foot
      posture), 0.96+/-0.17 (neutral foot posture) and 0.77+/-0.16 (pronated foot
      posture) and 1.25+/-0.24 (supinated foot posture), 1.06+/-0.23 (neutral foot
      posture) and 0.86+/-0.19 (pronated foot posture) in males. The regression model
      showed that foot posture and dynamic navicular drop (dND) were both associated
      with SaEn. CONCLUSION: This study confirmed that non-linear analysis is of
      relevance in the interpretation of kinematic data. Pronated foot posture, large
      navicular drop and women were characterized by low values of non-linear
      variability. Future studies should investigate if measurements of SaEn are
      capable of identifying subjects with an increased risk of injury.

PMID- 20129788
TI  - Gamma knife stereotactic radiosurgery yields good long-term outcomes for low
      volume uveal melanomas without intraocular complications.
AB  - We present the outcomes of 35 uveal melanoma patients treated with gamma knife
      stereotactic radiosurgery. All cases were previously untreated. During follow-up,
      regular MRI examinations were used to detect any changes in tumor size and
      estimate the local long-term tumor control rate. Treatment-related complications
      were also recorded. During follow-up, systemic dissemination was observed in two
      patients, one of whom died of metastases. The most frequent complication was
      retinal detachment (17.1%). Three patients required enucleation. Cumulative 1
      year and 3-year local tumor growth control rates were 97% and 83%, respectively.
      The mean and median times to local tumor progression were 48.0 and 51.7 months,
      respectively. Gamma knife surgery may be a suitable alternative for the treatment
      of low-volume uveal tumors without intraocular complications, as the control rate
      and long-term outcomes compare favorably with those of surgical excision and
      brachytherapy.

PMID- 20129789
TI  - Synthesis and carbohydrate binding studies of fluorescent alpha-amidoboronic
      acids and the corresponding bisboronic acids.
AB  - Fluorescent boronic acids are very useful for the design and synthesis of
      carbohydrate sensors. In an earlier communication, we first described the effort
      of developing water soluble fluorescent alpha-amidoboronic acids, which change
      fluorescence upon sugar binding. In this report, we describe a general method of
      functionalizing such boronic acids and their applications in the preparation of
      bis-alpha-amidoboronic acids with significantly enhanced binding for
      oligosaccharides as compared to their monoboronic acid counterparts. The
      advantages of good water solubility, easy modification to generate diversity, and
      modularity in synthesis will make alpha-amidoboronic acids very useful building
      blocks for future synthesis of boronic acid-based fluorescent sensors.

PMID- 20129790
TI  - Synthesis and cancer cell cytotoxicity of substituted xanthenes.
AB  - A series of substituted xanthenes was synthesized and screened for activity using
      DU-145, MCF-7, and HeLa cancer cell growth inhibition assays. The most potent
      compound, 9 g ([N,N-diethyl]-9-hydroxy-9-(3-methoxyphenyl)-9H-xanthene-3
      carboxamide), was found to inhibit cancer cell growth with IC(50) values ranging
      from 36 to 50 microM across all three cancer cell lines. Structure-activity
      relationship (SAR) data is presented that indicates additional gains in potency
      may be realized through further derivatization of the compounds (e.g., the
      incorporation of a 7-fluoro substituent to 9 g). Results are also presented that
      suggest the compounds function through a unique mechanism of action as compared
      to that of related acridine and xanthone anticancer agents (which have been shown
      to intercalate into DNA and inhibit topoisomerase II activity). A structural
      comparison of these compounds suggests the differences in function may be due to
      the structure of the xanthene heterocycle which adopts a nonplanar conformation
      about the pyran ring.

PMID- 20129791
TI  - 3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3
      receptor antagonists. part 2: optimization of the side chains to improve in vitro
      and in vivo potencies.
AB  - A series of 3-[2-{[(3-methyl-1-phenylbutyl)amino]carbonyl}-4
      (phenoxymethyl)phenyl]propanoic acid analogs were synthesized and evaluated for
      their in vitro potency. In most cases, introduction of one or two substituents
      into the two phenyl moieties resulted in the tendency of an increase or retention
      of in vitro activities. Several compounds, which showed excellent subtype
      selectivity, were evaluated for their inhibitory effect against PGE(2)-induced
      uterine contraction in pregnant rats, which is thought to be mediated by the EP3
      receptor subtype. The structure-activity relationships (SARs) are also discussed.

PMID- 20129792
TI  - Structural basis for selective inhibition of purine nucleoside phosphorylase from
      Schistosoma mansoni: kinetic and structural studies.
AB  - Selectivity plays a crucial role in the design of enzyme inhibitors as novel
      antiparasitic agents, particularly in cases where the target enzyme is also
      present in the human host. Purine nucleoside phosphorylase from Schistosoma
      mansoni (SmPNP) is an attractive target for the discovery of potential
      antischistosomal agents. In the present work, kinetic studies were carried out in
      order to determine the inhibitory potency, mode of action and enzyme selectivity
      of a series of inhibitors of SmPNP. In addition, crystallographic studies
      provided important structural insights for rational inhibitor design, revealing
      consistent structural differences in the binding mode of the inhibitors in the
      active sites of the SmPNP and human PNP (HsPNP) structures. The molecular
      information gathered in this work should be useful for future medicinal chemistry
      efforts in the design of new inhibitors of SmPNP having increased affinity and
      selectivity.

PMID- 20129793
TI  - Quinolinotriazole-beta-cyclodextrin and its adamantanecarboxylic acid complex as
      efficient water-soluble fluorescent Cd(2+) sensors.
AB  - A novel beta-cyclodextrin derivative 1 bearing 8-hydroxyquinolino and triazole
      groups was synthesized in satisfactory yield by 'click chemistry'. With a good
      water solubility up to 0.03 mol/L, 1 exhibited an effective switch-on
      fluorescence response to Cd(2+) over other common metal ions under physiological
      conditions. Studies on the recognition mechanism indicated that the cooperative
      coordination of Cd(2+) with both the 8-hydroxyquinolino moiety excluded from the
      beta-CD cavity and the triazole moiety was a crucial and basic factor to achieve
      the fluorescent sensing process. Significantly, spectrophotometric studies also
      demonstrated that, after inclusion complexation with 1-adamantanecarboxylic acid
      sodium salt (AdCA), the resultant 1/AdCA system gave a more effective fluorescent
      sensing to Cd(2+) through a cyclodextrin/substrate/Cd(2+) triple binding mode.

PMID- 20129794
TI  - Mitochondrial biotransformation of omega-(phenoxy)alkanoic acids, 3
      (phenoxy)acrylic acids, and omega-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids:
      a prodrug strategy for targeting cytoprotective antioxidants to mitochondria.
AB  - Mitochondrial reactive oxygen species (ROS) generation and the attendant
      mitochondrial dysfunction are implicated in a range of disease states. The
      objective of the present studies was to test the hypothesis that the
      mitochondrial beta-oxidation pathway could be exploited to deliver and
      biotransform the prodrugs omega-(phenoxy)alkanoic acids, 3-(phenoxy)acrylic
      acids, and omega-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids to the
      corresponding phenolic antioxidants or methimazole. 3- and 5-(Phenoxy)alkanoic
      acids and methyl-substituted analogs were biotransformed to phenols; rates of
      biotransformation decreased markedly with methyl-group substitution on the
      phenoxy moiety. 2,6-Dimethylphenol formation from the analogs 3-([2,6
      dimethylphenoxy]methylthio)propanoic acid and 3-(2,6-dimethylphenoxy)acrylic acid
      was greater than that observed with omega-(2,6-dimethylphenoxy)alkanoic acids. 3-
      and 5-(1-Methyl-1H-imidazol-2-ylthio)alkanoic acids were rapidly biotransformed
      to the antioxidant methimazole and conferred significant cytoprotection against
      hypoxia-reoxygenation injury in isolated cardiomyocytes. Both 3-(2,6
      dimethylphenoxy)propanoic acid and 3-(2,6-dimethylphenoxy)acrylic acid also
      afforded cytoprotection against hypoxia-reoxygenation injury in isolated
      cardiomyocytes. These results demonstrate that mitochondrial beta-oxidation is a
      potentially useful delivery system for targeting antioxidants to mitochondria.

PMID- 20129795
TI  - Applied Radiation and Isotopes. The 7th International Topical Meeting on
      Industrial Radiation and Radio isotope Measurement Application (IRRMA-7).
      Foreword.

PMID- 20129796
TI  - Homocysteine and pro-inflammatory cytokine concentrations in acute heart disease.
AB  - Inflammation is involved in development and progression of atherosclerosis.
      Interleukin-2 (IL-2) and interleukin-6 (IL-6) have been correlated with various
      cardiovascular diseases. Hyperhomocysteinemia is an important risk factor for
      atherosclerosis and thrombotic disease. Recent studies have demonstrated that
      homocysteine (Hcy) enhances productions of several pro-inflammatory cytokines. In
      the light of these findings, we decided to determine if any relationship exists
      between IL-2 and IL-6, the pro-inflammatory cytokines, and total homocysteine
      (tHcy) in acute coronary syndrome (ACS). A total of 102 patients with ACS and 90
      healthy subjects were included in the study. The levels of tHcy, IL-2 and IL-6
      were higher and folic acid was lower in patients as compared with those of
      controls. Furthermore, data of the area under ROC plot for IL-2 demonstrated that
      IL-2 had higher sensitivity. These data suggest that enhanced inflammation may be
      associated with tHcy-related cardiovascular disease.

PMID- 20129797
TI  - Infrared multiphoton dissociation of small-interfering RNA anions and cations.
AB  - Infrared multiphoton dissociation (IRMPD) on a linear ion trap mass spectrometer
      is applied for the sequencing of small interfering RNA (siRNA). Both single
      strand siRNAs and duplex siRNA were characterized by IRMPD, and the results were
      compared with that obtained by traditional ion trap-based collision induced
      dissociation (CID). The single-strand siRNA anions were observed to dissociate
      via cleavage of the 5' P-O bonds yielding c- and y-type product ions as well as
      undergo neutral base loss. Full sequence coverage of the siRNA anions was
      obtained by both IRMPD and CID. While the CID mass spectra were dominated by base
      loss ions, accounting for approximately 25% to 40% of the product ion current,
      these ions were eliminated through secondary dissociation by increasing the
      irradiation time in the IRMPD mass spectra to produce higher abundances of
      informative sequence ions. With longer irradiation times, however, internal ions
      corresponding to cleavage of two 5' P-O bonds began to populate the product ion
      mass spectra as well as higher abundances of [a - Base] and w-type ions. IRMPD of
      siRNA cations predominantly produced c- and y-type ions with minimal
      contributions of [a - Base] and w-type ions to the product ion current; the
      presence of only two complementary series of product ions in the IRMPD mass
      spectra simplified spectral interpretation. In addition, IRMPD produced high
      abundances of protonated nucleobases, [G + H](+), [A + H](+), and [C + H](+),
      which were not detected in the CID mass spectra due to the low-mass cut-off
      associated with conventional CID in ion traps. CID and IRMPD using short
      irradiation times of duplex siRNA resulted in strand separation, similar to the
      dissociation trends observed for duplex DNA. With longer irradiation times,
      however, the individual single-strands underwent secondary dissociation to yield
      informative sequence ions not obtained by CID.

PMID- 20129798
TI  - Bandpass characteristics of high-frequency sensitivity and visual experience in
      blindsight.
AB  - Patient RP suffers a unilateral right homonymous quadrant anopia but demonstrates
      better than chance discrimination for stimuli presented in the blind field at
      temporal frequencies between 33 and 47Hz (all significant at p<.05, binomial).
      Examination of her reports of visual experience during blind-field discrimination
      suggests a more complex picture in which experiences particular to correct
      discrimination are not found at low-mid-gamma frequencies, but are significantly
      more likely than average (76%, p<.001) at a lower frequency (22Hz) at which
      blindsight is not observed. We believe that visual experience may serve to
      support blindsight if discrimination tasks are generally impaired at frequencies
      outside of the low-mid-gamma band. If this is so, although generally experienced
      as non-specific and unstructured light, the visual experience that accompanies
      discrimination performance must be based upon a neural representation which
      includes information on the visual features present in the stimulus.

PMID- 20129799
TI  - Congenital stridor and wheezing as harbingers of the del22q11.2 syndrome
      presenting cardiovascular malformations of right aortic arch, aberrant left
      subclavian artery, Kommerell's diverticulum, and left ligamentum arteriosum.
AB  - A complete vascular ring composed of right aortic arch, aberrant left subclavian
      artery with Kommerell's diverticulum, and left ligamentum arteriosum was
      diagnosed by barium esophagography, echocardiography, angiography, and
      multidetector computed tomography of chest in an 18-day-old male neonate who
      presented with remarkable inspiratory stridor, expiratory wheezing, postprandial
      vomiting, and dysphagia since birth, and survived surgical division of the left
      ligamentum arteriosum, resection of the Kommerell's diverticulum, and
      reimplanation of the left subclavian artery to the left common carotid artery.
      Cytogenetic analysis and fluorescence in situ hybridization study of his blood
      revealed chromosome 22q11.2 deletion, with a karyotype of 46,XY.ish del(22)(q11.2
      q11.2). A constellation of right aortic arch, aberrant left subclavian artery
      with Kommerell's diverticulum, and left ligamentum arteriosum in neonates may
      cause refractory stridor, wheezing, vomiting, and dysphagia, which can serve as
      harbingers of the del22q11.2 syndrome.

PMID- 20129800
TI  - Aneurysms in the arteries of the upper extremity in a Kenyan population.
AB  - BACKGROUND: Aneurysms in the arteries of the upper extremity are rare but
      important in predicting aortic aneurysms and their potential to thromboembolize
      and cause limb loss. Their localization, age, and gender distribution vary
      between countries depending on ethnic background and cause. These data are
      valuable in the management of aneurysms, but are largely lacking from the Kenyan
      population. OBJECTIVE: This study aimed at examining the pattern of these
      aneurysms in a Kenyan population. STUDY DESIGN: Retrospective. SETTING: Kenyatta
      National Hospital, Kenya. PATIENTS AND METHODS: Hospital records of aneurysms in
      upper limb arteries over 10 years from January 1998 to December 2007 were
      examined. Ethical approval was given by the Kenyatta National Hospital Ethics and
      Research Committee. Site, age, gender, and risk factors were recorded.
      Unconfirmed diagnoses were excluded. Results were analyzed using SPSS 11.50 and
      presented using tables. RESULTS: Aneurysms of the upper extremity arteries
      comprise 34 (35.4%) out of 96 peripheral aneurysms. Of these, brachial artery was
      the most common site (35.3%), followed by brachiocephalic (11, 32.4%), subclavian
      (9, 26.5%), radial (1, 2.9%), and anterior interosseous (1, 2.9%). Trauma was the
      commonest predisposing factor (41.2%), followed by atherosclerosis and related
      comorbidities (32.4%), infection (11.8%), and autoimmune disease (8.8%). The mean
      age was 39.5 years (range: 13-79) with a variable gender distribution.
      CONCLUSION: Aneurysms of the upper extremity arteries are not uncommon in the
      Kenyan population. They occur more commonly in individuals aged 50 years and
      less, and although most of them are traumatic, atherosclerosis constitutes a
      significant proportion. Prudent management of risk factors is recommended.

PMID- 20129801
TI  - Effect of medication withdrawal on the interictal epileptiform EEG discharges in
      presurgical evaluation.
AB  - Medication withdrawal (MW) is an important method of provoking seizures and
      activating epileptiform EEG activity during the diagnostic work-up of patients
      evaluated for epilepsy surgery. Previously it was suggested that MW might
      influence the seizure-type and activate cortical areas otherwise not producing
      epileptiform discharges, leading to a false localization of the irritative zone.
      In order to investigate this we reviewed 42 consecutive cases of MW, of 36
      patients, during a 3-year period. We compared seizure frequency, seizure-types
      and the localization of interictal epileptiform discharges before and after MW.
      Seizure frequency was significantly higher after MW. In the whole group we found
      an increase in seizure propagation: the proportion of the complex partial
      seizures and secondarily generalised seizures increased, while the proportion of
      the simple partial seizures decreased following MW. In one-third of the patients
      the interictal EEGs after the MW were different from those recorded before the
      MW. However, in these discordant cases the EEG findings after the MW (and not
      before the MW) were concordant with the seizure onset zone and the lesional zone.
      We conclude that MW is an effective and reliable seizure provoking method, and it
      does not lead to false localization of the irritative zone.

PMID- 20129802
TI  - There is a growing realization of the important role of transcranial Doppler and
      intravenous antiplatelet therapy in the control of platelet microemboli and
      associated perioperative strokes.

PMID- 20129803
TI  - Sensitivity to antibiotics of Arcanobacterium pyogenes and Escherichia coli from
      the uteri of cows with metritis/endometritis.
AB  - The aim of the study was to determine the in vitro sensitivity of 161
      Arcanobacterium pyogenes strains and 99 Escherichia coli strains isolated from
      the uteri of 312 cows with metritis/endometritis. Animals with pathological
      discharges were clinically diagnosed per rectum and per vaginum, and then swabs
      from the lumen of the uterus were aseptically collected. Bacteriological
      examination of swabs was according to commonly accepted procedures with the
      additional use of API tests. Sensitivity to antibiotics was tested by the disk
      diffusion method and performed in Mueller-Hinton agar. Arc. pyogenes strains were
      the most sensitive to amoxicillin/clavulanic acid (Amc) (97.3%), bacitracin
      (96.7%), ceftiofur (95.8%) and cephapirin (77.5%). E. coli strains were the most
      sensitive to norfloxacin (98.1%), marbofloxacin (95.8%), gentamycin (88%), Amc
      (80.7%) and ceftiofur (73.1%). Arc. pyogenes and E. coli were most resistant to
      oxytetracycline (63.7% and 31%, respectively).

PMID- 20129804
TI  - 1H-detected 1H-1H correlation spectroscopy of a stereo-array isotope labeled
      amino acid under fast magic-angle spinning.
AB  - The combined use of selective deuteration, stereo-array isotope labeling (SAIL),
      and fast magic-angle spinning effectively suppresses the 1H-1H dipolar couplings
      in organic solids. This method provided the high-field 1H NMR linewidths
      comparable to those achieved by combined rotation and multiple-pulse
      spectroscopy. This technique was applied to two-dimensional 1H-detected 1H-1H
      polarization transfer CHH experiments of valine. The signal sensitivity for the
      1H-detected CHH experiments was greater than that for the 13C-detected 1H-1H
      polarization transfer experiments by a factor of 2-4. We obtained the 1H-1H
      distances in SAIL valine by CHH experiments with an accuracy of about 0.2A by
      using a theory developed for 1H-1H polarization transfer in 13C-labeled organic
      compounds.

PMID- 20129805
TI  - Sphericity of a protein via the beta-complex.
AB  - Molecular shape is a fundamental factor in determining the function of a
      molecule. As proteins tend to fold into globular shapes, the shape descriptor for
      protein sphericity is important in understanding molecular functions. In this
      paper, a definition of protein sphericity is introduced based on the recently
      developed geometric constructs of the beta-complex and beta-shape of a protein.
      The beta-complex represents the Euclidean proximity among all the atoms in a
      protein, and the beta-shape is the polyhedron contained within the boundary of
      the corresponding beta-complex. Hence, the beta-shape determines the proximity
      among the atoms on the boundary of a protein. Given the volume of a beta-shape,
      the ratio between the surface area of a sphere with this volume and the surface
      area of the beta-shape itself is a good measure to classify the sphericity of a
      protein, especially when the radius of a probe is 3.0 A. The presented measure is
      invariant to translation and rotation.

PMID- 20129806
TI  - Computed NMR shielding increments over benzo-analogs of unsaturated five-membered
      ring heterocyclic compounds as a measure of aromaticity.
AB  - The GIAO-HF method in Gaussian 03 was used to calculate the isotropic shielding
      value of the proximal hydrogen of a diatomic hydrogen probe moved in a square
      grid 2.5A above the plane of 15 benzo-fused analogs of conjugated five-membered
      ring heterocyclic compounds: pyrrole, furan, thiophene, and phosphole and their 2
      and 3-nitrogen analogs. Subtraction of the calculated isotropic shielding value
      of diatomic hydrogen from each of these isotropic shielding values gave the
      shielding increment (Delta sigma) for each probe position. Plotting this value
      against Cartesian coordinates of the probe position allowed determination of the
      computed through-space shielding increment surfaces for these compounds.
      Substantial shielding was observed above the center of each ring, as expected for
      aromatic compounds. The magnitude of the shielding increment 2.5A above the
      heterocyclic ring center correlated reasonably well with the only other published
      method of assessing aromaticity of these systems ASE (aromatic stabilization
      energy) and with our calculated NICS (nucleus-independent chemical shift) values,
      another magnetic criterion. The magnitude of the shielding increment measured
      over the benzene ring midpoint did not correlate well with other measures of
      aromaticity, however.

PMID- 20129807
TI  - Clinical issues and frequent questions about biotinidase deficiency.
AB  - Biotinidase deficiency is a biotin-responsive, inherited neurocutaneous disorder.
      The disorder is readily treatable and is screened for in the newborn period. Over
      the years since the discovery of the disorder, many practical questions and
      issues have been raised as to the diagnosis, management, treatment, and newborn
      screening of the disorder. In this paper, many of these issues are addressed
      using evidence-based medicine and anecdotal experiences. If adequate answers are
      not known, the answers to these queries will require future investigations.

PMID- 20129809
TI  - Evaluating geographic variation in type 1 and type 2 diabetes mellitus incidence
      in youth in four US regions.
AB  - We evaluated geographic variation in type 1 and type 2 diabetes mellitus (T1DM,
      T2DM) in four regions of the United States. Data on 807 incident T1DM cases
      diabetes and 313 T2DM cases occurring in 2002-03 in South Carolina (SC) and
      Colorado (CO), 5 counties in Washington (WA), and an 8 county region around
      Cincinnati, Ohio (OH) among youth aged 10-19 years were obtained from the SEARCH
      for Diabetes in Youth Study. Geographic patterns were evaluated in a Bayesian
      framework. Incidence rates differed between the study regions, even within
      race/ethnic groups. Significant small-area variation within study region was
      observed for T1DM and T2DM. Evidence for joint spatial correlation between T1DM
      and T2DM was present at the county level for SC (r(SC)=0.31) and CO non-Hispanic
      Whites (r(CO)=0.40) and CO Hispanics (r(CO)=0.72). At the tract level, no
      evidence for meaningful joint spatial correlation was observed (r(SC)=-0.02;
      r(CO)=-0.02; r(OH)=0.03; and r(WA=)0.09). Our study provides evidence for the
      presence of both regional and small area, localized variation in type 1 and type
      2 incidence among youth aged 10-19 years in the United States.

PMID- 20129810
TI  - siRNAs and DNA methylation: seedy epigenetics.
AB  - To understand how DNA sequence is translated to phenotype we must understand the
      epigenetic features that regulate gene expression. Recent research illuminates
      the complex interactions between DNA methylation, small RNAs, silencing of
      transposable elements, and genomic imprinting in the Arabidopsis (Arabidopsis
      thaliana) seed. These studies suggest that transposable elements reactivated in
      specific cells of the gametophyte and seed might enhance silencing of
      transposable elements in the germline and embryo. By sacrificing genomic
      integrity these cells might make an epigenetic rather than genetic contribution
      to the progeny. This research could have implications for interspecies
      hybridization, the evolution of genomic imprinting, and epigenetic communication
      from plant to progeny.

PMID- 20129811
TI  - The use of video-keratoscopy in predicting contact lens parameters for
      keratoconic fitting.
AB  - PURPOSE: The purpose of this report is to demonstrate the use the video
      keratoscope in determining the type and size of the cone in keratoconus and PMD
      patients and the final back optic zone diameter (BOZD) and total lens diameter
      (LD). METHODS: A retrospective review of one hundred clinical records including
      topographic maps, of keratoconic patients (randomly selected) was performed. Cone
      diameter and type and final contact lens base curve and diameter were recorded.
      RESULTS: The types or variations of keratoconus were determined with the use of
      the tangential map to be either: centred or nipple, early oval cones, moderate
      oval cones, severe cones or pellucid marginal degeneration (PMD). The size of the
      cone was dependent on the type and the stage of progression of the cone.
      Inventory sets for keratoconus that had progressively smaller BOZDs as the base
      curve or back optic zone radius (BOZR) steepened were found to fit best when
      prescribed for centred or nipple cones. Inventory sets or multicurve sets that
      had a constant BOZD with a certain lens diameter that did not vary with the BOZR
      were found to perform better on oval cones. Very large cones, as with PMD
      benefited from lenses with very large BOZDs. CONCLUSIONS: Matching the size of
      the BOZD (and in tandem the LD) to the size of the cone as determined with the
      tangential topographic map may be a useful tool in aiding in contact lens fitting
      to increase success.

PMID- 20129812
TI  - New structures, chemical functions, and inhibitors for glycosyltransferases.
AB  - Glycosyltransferases are key enzymes in a range of biological processes. The last
      two years have seen a new appreciation for the range of structural folds that can
      be adopted by this class of enzymes in addition to continued work in solving the
      structures of more varieties of these proteins, delineating their chemical
      function, and designing inhibitors of their catalytic function.

PMID- 20129813
TI  - Comment on: "FTIR, FT-Raman, scaled quantum chemical studies of the structure and
      vibrational spectra of 1,5-dinitronaphthalene" by Arivazhaga et al. [Spectrochim.
      Acta A72 (2009) 941-946].
AB  - The title paper [1] reports ab initio calculations of the structure and molecular
      vibrations of 1,5-dinitronaphthalene. The calculations are unminimised, the
      molecular structure is wrong and the vibrational spectra are misinterpreted.
      These errors have been corrected and the vibrational spectra of 1,5
      dinitronaphthalene have been reassigned in agreement with the optical and neutron
      spectroscopic data.

PMID- 20129814
TI  - Intramolecular deactivation processes in complexes of salicylic acid or glycolic
      acid with Eu(III).
AB  - The complexation of Eu(III) by 2-hydroxy benzoic acid (2HB) or glycolic acid (GL)
      was investigated using steady-state and time-resolved laser spectroscopy.
      Experiments were carried out in H(2)O as well as in D(2)O in the temperature
      range of 80K<T<290K. The Eu(III) luminescence spectra and luminescence decay
      times were evaluated with respect to the temperature dependence of (i) the
      luminescence decay time tau, (ii) the energy of the D5(0)-->F7(0) transition,
      (iii) the width of the D5(0)-->F7(0) transition, and (iv) the asymmetry ratio
      calculated from the luminescence intensities of the D5(0)-->F7(2) and D5(0)-
      >F7(1) transition, respectively. The differences in ligand-related luminescence
      quenching are discussed. Based on the temperature dependence of the luminescence
      decay times an activation energy for the ligand-specific non-radiative
      deactivation in Eu(III)-2HB or Eu(III)-GL complexes was determined. It is
      stressed that ligand-specific quenching processes (other than OH quenching
      induced by water molecules) need to be determined and considered in detail, in
      order to extract speciation-relevant information from luminescence data (e.g.,
      estimation of the number of water molecules n(H(2)0) in the first coordination
      sphere of Eu(III)). In case of 2HB, conclusions drawn from the evaluation of the
      Eu(III) luminescence are compared with results of a X-ray structure analysis.

PMID- 20129815
TI  - An ATR-FTIR study of different phosphonic acids adsorbed onto boehmite.
AB  - An ATR-FTIR study of the vibrational spectra of N,N-bis(2-hydroxyethyl)
      aminomethylphosphonic acid (BHAMP), 1-hydroxyethane-1,1'-diphosphonic acid (HEDP)
      and nitrilotris(methylenephosphonic acid) (NTMP) adsorbed onto boehmite is
      presented. The study was performed in the pH range from 5 to 9, and bands
      assignments are given in the 1200-900 cm(-1) wavenumber range, where the bands
      associated with various P-O(H) vibrations can be found. The three phosphonic
      acids adsorb onto boehmite by forming inner-sphere surface complexes. ATR-FTIR
      data indicates the presence of both protonated and deprotonated mononuclear
      surface species. In all cases, the surface-bound ions undergo protonation
      reactions as pH is decreased. The results are in good agreement with previously
      proposed surface complexation models.

PMID- 20129816
TI  - Compact broadband vibrational sum-frequency generation spectrometer with
      nonresonant suppression.
AB  - A compact broadband vibrational sum-frequency spectroscopy (SFG) apparatus is
      described to study molecules at surfaces and interfaces. Using an etalon as the
      frequency narrowing device, the visible pulse has a time-asymmetric profile that
      allows the user to deeply suppress nonresonant background signals that hinder
      detection of molecular vibrational resonances. Several features of the
      spectrometer that, in aggregate, improve signal-to-noise ratios by a large factor
      are described. The spectrometer features a series of interchangeable prealigned
      sample holders for different applications. Examples of applications are presented
      where nonresonant suppression greatly improves the ability to study adsorbates on
      single-crystal surfaces as a function of rotation about the azimuth, and where
      the rapid data acquisition abilities of the spectrometer are used to study
      electrochemical transformations on single-crystal electrodes.

PMID- 20129817
TI  - Spectrophotometric determination of sildenafil citrate in pure form and in
      pharmaceutical formulation using some chromotropic acid azo dyes.
AB  - Two simple and highly sensitive spectrophotometric methods were developed for the
      quantitative determination of the drug sildenafil citrate (SC), Viagra, in pure
      form and in pharmaceutical formulations, through ion-associate formation
      reactions (method A) with mono-chromotropic acid azo dyes, chromotrope 2B (I) and
      chromotrope 2R (II) and ion-pair reactions (method B) with bi-chromotropic acid
      azo dyes, 3-phenylazo-6-o-carboxyphenylazo-chromotropic acid (III), bis-3,6-(o
      hydroxyphenylazo)-chromotropic acid (IV), bis-3,6-(p-N,N-dimethylphenylazo)
      chromotropic acid (V) and 3-phenylazo-6-o-hydroxyphenylazo-chromotorpic acid
      (VI). The reaction products, extractable in methylene chloride, were
      quantitatively measured at 540, 520, 540, 570, 600 and 575 nm using reagents, I
      VI, respectively. The reaction conditions were studied and optimized. Beer's
      plots were linear in the concentration ranges 3.3-87.0, 3.3-96.0, 5.0-115.0, 2.5
      125.0, 8.3-166.7 and 0.8-15.0 microg mL(-1) with corresponding molar
      absorptivities 1.02 x 10(4), 8.34 x 10(3), 6.86 x 10(3), 5.42 x 10(3), 3.35 x
      10(3) and 2.32 x 10(4)Lmol(-1) cm(-1) using reagents I-VI, respectively. The
      limits of detection and Sandell's sensitivities were calculated. The methods were
      successfully applied to the analysis of commercial tablets (Vigoran) and the
      recovery study reveals that there is no interference from the common excipients
      that are present in tablets. Statistical comparison of the results was performed
      with regard to accuracy and precision using Student's t- and F-tests at 95%
      confidence level. There is no significant difference between the reported and
      proposed methods with regard to accuracy and precision.

PMID- 20129818
TI  - Solid state and solution study of some phosphoramidate derivatives containing the
      P(O)NHC(O) bifunctional group: crystal structures of
      CCl(2)HC(O)NHP(O)(NCH(3)(CH(2)C(6)H(5)))(2), p
      ClC(6)H(4)C(O)NHP(O)(NCH(3)(CH(2)C(6)H(5)))(2),
      CCl(2)HC(O)NHP(O)(N(CH(2)C(6)H(5))(2))(2) and p
      BrC(6)H(4)C(O)NHP(O)(N(CH(2)C(6)H(5))(2))(2).
AB  - Synthetic methods for several novel phosphoramidate compounds containing the
      P(O)NHC(O) bifunctional group were developed. These compounds with the general
      formula R(1)C(O)NHP(O)(N(R(2))(CH(2)C(6)H(5)))(2), where R(1)=CCl(2)H, p
      ClC(6)H(4), p-BrC(6)H(4), o-FC(6)H(4) and R(2)=hydrogen, methyl, benzyl, were
      characterized by several spectroscopic methods and analytical techniques. The
      effects of phosphorus substituents on the rotation rate around the P-N(amine)
      bond were also investigated. (1)H NMR study of the synthesized compounds
      demonstrated that the presence of bulky groups attached to the phosphorus center
      and electron withdrawing groups in the amide moiety lead to large chemical-shift
      non-equivalence (Deltadelta(H)) of diastereotopic methylene protons. The crystal
      structures of CCl(2)HC(O)NHP(O)(NCH(3)(CH(2)C(6)H(5)))(2), p
      ClC(6)H(4)C(O)NHP(O)(NCH(3)(CH(2)C(6)H(5)))(2),
      CCl(2)HC(O)NHP(O)(N(CH(2)C(6)H(5))(2))(2) and p
      BrC(6)H(4)C(O)NHP(O)(N(CH(2)C(6)H(5))(2))(2) were determined by X-ray
      crystallography using single crystals. The coordination around the phosphorus
      center in these compounds is best described as distorted tetrahedral and the P(O)
      and C(O) groups are anti with respect to each other. In the compound Br
      C(6)H(4)C(O)NHP(O)(N(CH(2)C(6)H(5))(2))(2) (with two independent molecules in the
      unit cell), two conformers are connected to each other via two different N-H...O
      hydrogen bonds forming a non-centrosymmetric dimer. In the crystalline lattice of
      other compounds, the molecules form centrosymmetric dimers via pairs of same N
      H...O hydrogen bonds. The structure of CCl(2)HC(O)NHP(O)(N(CH(2)C(6)H(5))(2))(2)
      reveals an unusual intramolecular interaction between the oxygen of C=O group and
      amine nitrogen.

PMID- 20129819
TI  - Ab initio Hartree-Fock and density functional theory study on characterization of
      3-(5-methylthiazol-2-yldiazenyl)-2-phenyl-1H-indole.
AB  - The optimized molecular structures, vibrational frequencies, corresponding
      vibrational assignments, thermodynamic properties, UV-vis spectra and atomic
      charges of 3-(5-methylthiazol-2-yldiazenyl)-2-phenyl-1H-indole molecule have been
      investigated using ab initio Hartree-Fock (HF) and density functional theory
      (B3LYP) methods at 6-31G (d,p) basis set. The obtained bond lengths and bond
      angles have been seen to be good agreement with the experimental data. After
      calculated vibrational frequencies have been compared with each other, the
      correlation coefficient has been determined. Moreover, we have not only simulated
      highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital
      (LUMO) but also determined the transition state and energy band gap. Infrared
      intensities and Raman activities have been also reported.

PMID- 20129820
TI  - Agents applied in health care: A review.
AB  - PURPOSE: The agent-oriented paradigm has emerged as a viable approach for the
      development of autonomic systems in the healthcare domain. This paper reviews
      representative works in this area in order to identify the main research lines
      and study their level of applicability. Moreover, from the analysis of those
      works and the authors' own experiences, some lines of future research are
      suggested. METHODS: This paper presents a review of the literature (2002-2008) of
      applications of agents in healthcare collected from medical databases as well as
      international conferences. RESULTS: 15 agent-based systems were selected
      according to a set of criteria of work relevancy. Their internal architecture as
      well as communication-based coordination techniques were reviewed. A
      classification considering the main goal of the systems has been made. For each
      category, a discussion of the suitability of agent technology in resolving
      healthcare problems is presented. CONCLUSIONS: Agent-based systems offer added
      values over classical software approaches (e.g., reusability, reliability,
      flexibility, robustness, maintainability and adaptability). Furthermore, agent
      technology supports the integration of legacy systems, tackling the shortcomings
      of centralised systems, such as performance bottlenecks, resource limitations,
      and different kinds of failures. During the review, we found a huge number of
      contributions in this area, showing a growing interest of researchers. However,
      most of the analysed systems are only prototypes, they are not widely deployed in
      real environments and they are difficult to extend to others domains. Several
      aspects (security, reusability, modularity, personalisation, system maintenance)
      should be studied carefully in the next years in order to bring agent technology
      to real settings.

PMID- 20129821
TI  - A case of reversible restless legs syndrome (RLS) and sleep-related eating
      disorder relapse triggered by acute right leg herpes zoster infection: literature
      review of spinal cord and peripheral nervous system contributions to RLS.
AB  - Restless legs syndrome (RLS) is thought to be due to abnormalities of iron
      metabolism in the central nervous system; however, occasional cases are
      associated with lesions of the spinal cord, spinal rootlets, and peripheral
      nervous system. This is a case report of RLS exacerbated by shingles with a
      review of the literature of extra-cerebral lesions or disorders causing or
      contributing to RLS.

PMID- 20129822
TI  - Bisphosphonate-related osteonecrosis of the jaw in cancer patients: Implications
      for nurses.
AB  - PURPOSE: This paper reports a review of the literature with a specific focus on
      osteonecrosis of the jaw. Bisphosphonate drugs are commonly used in the treatment
      of bone disease secondary to myeloma and solid tumours, such as breast and
      prostate cancer. In the past few years, an uncommon but distressing condition
      known as osteonecrosis of the jaw (ONJ) has been detected in patients who are
      having bisphosphonate treatment, particularly the intravenous (IV) preparations.
      Osteonecrosis of the jaw results from bone exposure in the oral cavity with
      subsequent death of bone tissue (necrosis). METHOD: The review searched key
      databases including Medline, British Nursing Index, Cochrane, and meeting
      abstracts to ascertain the extent of literature in this field. RESULTS: Fourty
      two articles were reviewed which described the clinical manifestations of ONJ,
      the reported incidence and clinical cases. CONCLUSION: The results indicate there
      is an emerging body of evidence in this field and nurses delivering
      bisphosphonates need to familiarise themselves with the current guidance to
      ensure risks are minimised for patients.

PMID- 20129823
TI  - Variation in guideline adherence in intrauterine insemination care.
AB  - Health-care delivery according to clinical practice guidelines is thought to be
      critical in achieving optimal outcomes. This study aimed to assess the extent to
      which practice performance in intrauterine insemination (IUI) care is consistent
      with guideline recommendations and to evaluate the association between guideline
      adherence and outcome of IUI care. In a retrospective cohort study, 1100
      infertile couples who underwent IUI treatment at 10 Dutch hospitals were asked to
      grant access to their medical record for assessment of guideline adherence using
      25 systematically developed guideline-based performance indicators. A total of
      558 couples who started 2334 IUI cycles participated. Guideline adherence
      regarding 20 process and five structure aspects of IUI care was often substandard
      and varied considerably between hospitals. Out of 10 possible associations
      investigated, guideline adherence regarding sperm quality and guideline adherence
      regarding the total number of IUI cycles were associated with improved ongoing
      pregnancy rates after IUI. Thus, guideline adherence in IUI care is far from
      optimal and varies substantially between hospitals. As associations between
      guideline adherence and ongoing pregnancy after IUI were mainly non-significant,
      further research is needed to evaluate associations between guideline adherence
      and other outcomes of IUI care besides ongoing pregnancy, such as patient safety
      and cost effectiveness.

PMID- 20129824
TI  - Reduction in exposure of human embryos outside the incubator enhances embryo
      quality and blastulation rate.
AB  - Embryo quality is strongly dependent on the in-vitro culture environment.
      Conventionally, IVF/intracytoplasmic sperm injection (ICSI) embryos are examined
      microscopically every morning (from day 1 to day 6) to assess fertilization,
      cleavage and embryo quality. Consequently, the frequent exposure to non-optimal
      conditions outside the incubator may adversely affect embryonic viability and
      quality. Hence, this study investigated whether reduction of observation
      frequency outside the incubator can enhance blastocyst formation rate. A total of
      285 IVF/ICSI cycles were divided into two groups. Embryos in the control group
      (103 cycles) were assessed out-of-incubator every day after insemination (day 1
      to day 6; six times). In the experimental group (182 cycles), embryos were
      assessed four times, on days 1, 3, 5 and 6. The total blastocyst formation rate,
      day-5 blastocyst formation rate, proportion of good blastocysts and number of
      cryopreserved blastocysts per patient were significantly lower for the control
      group compared with the experimental group (42.5%, 31.4%, 50.7%, 1.72+/-1.55
      versus 52.6%, 40.7%, 60.1%, 2.64+/-2.59, respectively, P<0.05); although there
      were no significant differences in the proportions of good embryos on day 3,
      blastocyst formation rate on day 6, clinical pregnancy rate and implantation
      rate. Hence, reduction of the observation frequency of embryos outside the
      incubator can enhance embryo quality and blastocyst formation rate.

PMID- 20129825
TI  - Culture of human oocytes with granulocyte-macrophage colony-stimulating factor
      has no effect on embryonic chromosomal constitution.
AB  - The effect on ploidy rate in donated human oocytes after in-vitro culture with
      recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF; 2
      ng/ml) from fertilization until day 3 was examined in a multicentre, prospective
      placebo-controlled and double-blinded study including 73 women donating 86
      oocytes. The primary endpoint was to investigate the chromosomal constitution of
      human embryos (fluorescence in-situ hybridization analysis for chromosomes 13,
      16, 18, 21, 22, X and Y) cultured with or without GM-CSF. The secondary endpoints
      were number of top-quality embryos (TQE) and number of normally developed embryos
      evaluated morphologically on day 3. The cytogenetic analyses demonstrated non
      inferiority and therefore the chromosomal constitution of human embryos cultured
      in vitro in the presence of 2 ng/ml GM-CSF was no worse than the control group
      cultured without GM-CSF. In-vitro culture of human embryos in the presence of 2
      ng/ml GM-CSF resulted in 34.8% (8/23) uniformly normal embryos. Culture without 2
      ng/ml GM-CSF resulted in 33.3% (9/27) uniformly normal embryos. A trend towards a
      higher number of TQE in the test group was observed; however, due to lack of TQE
      in the control group, this was considered a random finding.

PMID- 20129826
TI  - Prospective randomized study for hydrotubation versus no hydrotubation before
      intrauterine insemination in unexplained infertility.
AB  - The purpose of the study was to investigate the value of hydrotubation before
      intrauterine insemination (IUI). In 228 patients with the diagnosis of
      unexplained infertility, ovarian stimulation was performed before IUI, using
      100mg of clomiphine citrate for 5 days from day 3 of the cycle and one ampoule of
      human menopausal gonadotrophin for 5 days from day 6 of the cycle. Folliculometry
      and determination of LH concentration in urine were performed daily until LH
      became positive, then randomization for hydrotubation before IUI versus no
      hydrotubation was performed. Fifteen patients were cancelled from the study due
      to poor response or stimulation of three or more follicles. A total of 213
      patients were randomized as follows: 103 patients undergoing hydrotubation using
      50 ml of saline and 110 patients with no hydrotubation. IUI was performed the
      following day and ongoing pregnancy occurred in 13 patients (12.6%) in the
      hydrotubation group and nine patients (8.2%) in the non-hydrotubation group with
      no significant difference (OR 1.66; 95% CI 0.62-4.63). In conclusion,
      hydrotubation before IUI does not improve pregnancy rate.

PMID- 20129827
TI  - Experiences of offspring searching for and contacting their donor siblings and
      donor.
AB  - This study investigates a new phenomenon whereby individuals conceived by donor
      insemination are searching for and contacting their donor and/or 'donor siblings'
      (i.e. donor offspring conceived by the same donor who are their genetic half
      siblings). On-line questionnaires were completed by members of the Donor Sibling
      Registry (DSR), a US-based registry that facilitates contact between donor
      conception families who share the same donor. Of the 165 donor offspring who
      completed the survey, 15% were searching for their donor siblings, 13% were
      searching for their donor, and 64% were searching for both. Differences were
      found according to family type and age of disclosure. Fewer offspring from
      heterosexual couple families had told their father about their search when
      compared with offspring from lesbian couple families who had told their co
      parent. Offspring who had found out about their conception after age 18 were more
      likely to be searching for medical reasons, whereas those who had found out
      before age 18 tended to be searching out of curiosity. Some offspring had
      discovered large numbers of half siblings (maximum=13). The majority of offspring
      who had found their donor relations reported positive experiences and remained in
      regular contact with them.

PMID- 20129828
TI  - Sweat production and the sympathetic skin response: improving the clinical
      assessment of autonomic function.
AB  - The aim of this project was to establish the relationship between sweat
      production and the electrodermal events comprising the sympathetic skin response
      to arousal stimuli. A series of randomly timed magnetic stimuli were applied to
      the neck of healthy human volunteers. Sympathetic skin responses and the
      associated sweat responses were recorded from the palms of both hands.
      Sympathetic skin responses typically had a biphasic shape consisting of a
      negative initial potential (palm relative to dorsum of hand) followed by a
      positive deflection. Sweat production was positively correlated with amplitude of
      the second positive deflection of the sympathetic skin response and negatively
      correlated with the amplitude of the initial negative deflection. For subjects
      showing only an initial negative sympathetic skin response, sweat release was low
      or not detectable. During habituation, the negative initial wave increased
      relative to the second positive wave, and sweat production fell. The strong
      correlation between the positive wave of the sympathetic skin response and sweat
      production suggests that the former may provide a quantitative functional measure
      of sudomotor activity in situations when it is impractical to measure the amount
      of sweat produced in the startle response. Thus, the positive component of the
      biphasic sympathetic skin response may be employed in clinical assessment of the
      functional efficacy of the sympathetic sudomotor system.

PMID- 20129829
TI  - Lack of association between genetic polymorphisms affecting sympathetic activity
      and tilt-induced vasovagal syncope.
AB  - Although the pathophysiology of vasovagal syncope is not completely understood,
      the involvement of sympathetic nervous system alterations has been suggested.
      Since predisposition to fainting during orthostatic challenge may be associated
      with genetic variations, we sought to explore the role of genetic polymorphisms
      affecting sympathetic nervous system function in the susceptibility to tilt
      induced vasovagal syncope. We genotyped 129 subjects with recurrent unexplained
      syncope who underwent tilt testing, and investigated the recurrence of syncope.
      The analysed polymorphisms were Arg492Cys (ADRA1A gene), Ser49Gly and Arg389Gly
      (ADRB1), Arg16Gly and Gln27Glu (ADRB2), 825C/T (GNB3), -1021C/T (DBH) and S/L
      (SLC6A4). No association of the aforementioned genetic variants with both tilt
      test outcomes and new syncopal episodes during follow-up was found. None of the
      considered polymorphisms influencing sympathetic activity is a major risk factor
      for vasovagal syncope in Italian patients.

PMID- 20129830
TI  - Archaeal DNA uracil repair via direct strand incision: A minimal system
      reconstituted from purified components.
AB  - Hydrolytic deamination of DNA cytosine residues results in U/G mispairs, pre
      mutagenic lesions threatening long-term genetic stability. Hence, DNA uracil
      repair is ubiquitous throughout all extant life forms and base excision repair,
      triggered by a uracil DNA glycosylase (UDG), is the mechanistic paradigm adopted,
      as it seems, by all bacteria and eukaryotes and a large fraction of archaea.
      However, members of the UDG superfamily of enzymes are absent from the extremely
      thermophilic archaeon Methanothermobacter thermautotrophicus DeltaH. This
      organism, as a hitherto unique case, initiates repair by direct strand incision
      next to the DNA-U residue, a reaction catalyzed by the DNA uridine endonuclease
      Mth212, an ExoIII homologue. To elucidate the detailed mechanism, in particular
      to identify the molecular partners contributing to this repair process, we
      reconstituted DNA uracil repair in vitro from only four purified enzymes of M.
      thermautotrophicus DeltaH. After incision at the 5'-side of a 2'-d-uridine
      residue by Mth212 DNA polymerase B (mthPolB) is able to take over the 3'-OH
      terminus and carry out repair synthesis generating a 5'-flap structure that is
      resolved by mthFEN, a 5'-flap endonuclease. Finally, DNA ligase seals the
      resulting nick. This defines mechanism and minimal enzymatic requirements of DNA
      U repair in this organism.

PMID- 20129831
TI  - [Right aortic arch with ductal ligament and diverticulum of Kommerell].

PMID- 20129832
TI  - [Scarlet fever variant of staphylococcal scalded skin syndrome].

PMID- 20129833
TI  - Lip cancer: a 5-year review in a tertiary referral centre.
AB  - INTRODUCTION: Lip cancer is second only to skin cancer in terms of frequency in
      the head and neck region. Surgery is the treatment of choice for most of these
      cancers. Although there are several strategies to reconstruct lip tumours after
      tumour ablation, scarce attention has been paid to the impact of the specific
      reconstructive modality on recurrence and survival. PATIENTS AND METHODS: A
      retrospective review of 228 patients treated for lip cancer in the Head and Neck
      Surgery Department of the Portuguese Institute of Oncology Francisco Gentil,
      Lisbon, Portugal, from 1993 to 2000 with at least 2 years of follow-up was
      conducted. All the cases were evaluated for demographic features, tumour
      characteristics, lip reconstructive surgery used and recurrence and survival.
      RESULTS: There were 184 male and 44 female patients (4:1 ratio), with an average
      age of 67.6+/-13.3 years. Most tumours were squamous cell carcinomas (94.7%), and
      were located in the lower lip (99.5%). Squamous cell carcinomas were well
      differentiated in 70.8% of cases. Tumour size and neck staging were strongly
      correlated (Pearson's coefficient of 0.805; p<0.001). Microscopical signs of
      neuroinvasion or lymphatic invasion were associated an increased risk of death
      due to cancer (chi-square=18.5; df=3; p=0.016). The different strategies used for
      lip reconstruction after tumour ablation did not differ significantly in the
      probability of later recurrence or death. CONCLUSIONS: Our data seem to lend
      support to the classical view that the most significant aspect of lip cancer
      surgery is tumour ablation, and that this is not affected by the subsequent
      reconstructive strategy. Hence, this seems to indicate that experienced surgeons
      are rightly not willing to compromise complete excision of the tumour for the
      sake of an easier or better reconstruction.

PMID- 20129834
TI  - A new approach to the antecubital scar contracture: rhomboid rotation flap.

PMID- 20129835
TI  - Use of the scratch pad for granulation tissue debridement.

PMID- 20129836
TI  - Management of primary cutis verticis gyrata with tissue expansion and hairline
      lowering foreheadplasty.

PMID- 20129837
TI  - Trainees assisting in private practice--are they covered?

PMID- 20129838
TI  - Screening for the metabolic syndrome using simple anthropometric measurements in
      south Asian and white Europeans: a population-based screening study. The
      Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) Study.
AB  - AIMS: To estimate the prevalence of metabolic syndrome in a general population
      sample of south Asians and white Europeans and compare predictors of metabolic
      syndrome, using ethnic specific definitions of obesity. METHODS: 3099
      participants (71.4% white European, 28.6% south Asian) aged 40-75 years were
      screened using a 75 g oral glucose tolerance test. Metabolic syndrome was defined
      using National Cholesterol Education Programme and International Diabetes
      Federation definitions. We compared sensitivity, specificity and area under the
      curve of waist circumference, body mass index and waist-hip ratio. RESULTS: The
      prevalence of metabolic syndrome using the definitions above was 29.9% (29.2%
      south Asian, 30.2% white European), and 34.4% (34.2% south Asian, 34.5% white
      European), respectively. Using the National Cholesterol Education Programme
      definition, waist circumference was significantly more predictive of metabolic
      syndrome than body mass index or waist-hip ratio. The area under the curve for
      waist circumference was 0.75 (95% CI: 0.69-0.80) and 0.76 (0.72-0.81) for south
      Asian men and women; 0.83 (0.80-0.85) and 0.80 (0.77-0.82) for white European men
      and women. CONCLUSIONS: The prevalence of metabolic syndrome is high in both
      south Asian and white European populations. Waist circumference is a simple and
      effective measure for predicting metabolic syndrome in different populations.

PMID- 20129839
TI  - Melanocortin 1 receptor (MC1R), pigmentary characteristics and sun exposure:
      findings from a case-control study of diffuse large B-cell and follicular
      lymphoma.
AB  - The relationship between skin cancer and non-Hodgkin lymphoma (NHL) suggests
      common genetic, host or environmental causes. Ultraviolet radiation (UVR),
      pigmentary characteristics have been linked with both malignancies, and for skin
      cancer, the melanocortin 1 receptor (MC1R) which influences pigmentation has also
      been implicated. This paper reports on the relationship between MC1R, skin, hair
      and eye colour, time spent outdoors, and diffuse large B-cell lymphoma (DLBCL)
      and follicular lymphoma (FL). Persons carrying MC1R homozygote variant alleles at
      R151C, R160W, D294H and D84E were more likely to have fair skin, red hair and to
      spend less time outdoors than those who did not. The variant allele at V92M was
      associated with FL (odds ratio (OR)=1.61, 95% confidence interval (CI) 1.08-2.39)
      and the r:wild type genotype with DLBCL (OR=0.58, 95% CI 0.38-0.89). Interactions
      between MC1R genotypes and skin colour influenced DLBCL risk; the RR genotype
      increased risk in individuals with medium or dark skin, based on 5 cases and no
      controls, but decreased risk among those of fair skin. On the whole, DLBCL and FL
      risk were not related to genetic variation in MC1R, pigmentation or time spent
      outdoors.

PMID- 20129840
TI  - Immunoprecipitation of nucleosomal DNA is a novel procedure to improve the
      sensitivity of serum screening for the p16 hypermethylation associated with colon
      cancer.
AB  - BACKGROUND: We developed a novel method of methylation-specific PCR (MSP) using
      immunoprecipitation with anti-histone antibody (IP-MSP) to efficiently detect
      serum methylated DNA tightly bound to de-acetylated histones. MATERIALS AND
      METHODS: The detection limit of IP-MSP for p16 methylation was determined with a
      standard made by cell line (SKCO-1) lysate. p16 methylation of tumor and/or serum
      of 51 colorectal cancers and 10 adenoma patients, and 10 healthy volunteers was
      detected with conventional MSP or IP-MSP. RESULTS: IP-MSP detected p16
      methylation from 0.5pg/mul of the cell lysate. The sensitivity of IP-MSP for
      detecting serum p16 methylation in 27 patients with tumors characterized by p16
      methylation was significantly higher than that with conventional method (81%
      versus 59%), particularly in Stage II patients (91% versus 45%). IP-MSP detected
      no p16 hypermethylation in sera of adenoma patients and volunteers. CONCLUSIONS:
      IP-MSP is thus considered to be a promising procedure to detect serum methylated
      DNA in colorectal cancer patients.

PMID- 20129841
TI  - Renal cell cancer in Israel: sex and ethnic differences in incidence and
      mortality, 1980-2004.
AB  - BACKGROUND: The causes of renal cell cancer (RCC) remain largely unexplained.
      While the incidence is generally higher in men than in women, little has been
      reported on ethnic differences. We examine trends in RCC incidence and mortality
      rates among Israeli Arab and Jewish populations and compared with the rates in
      other countries. METHODS: Age-adjusted RCC incidence and mortality rates in
      Israel, during 1980-2004, were calculated by sex and population group, using the
      National Cancer Registry. They were compared with the United States based on the
      Surveillance Epidemiology and End Results [SEER] program and the IARC database
      for international comparisons. RESULTS: While RCC incidence rates in Israel are
      similar to the United States and the European average, the rates are
      significantly higher among Israeli Jews than Arabs. Men are affected more than
      women. Incidence rates over the last 24 years have increased among all men and
      Jewish women, but not among Arab women. Among men, the incidence rate ratio for
      Jews to Arabs declined from 3.96 in 1980-1982 to 2.34 in 2001-2004, whereas for
      women there was no change. The mortality rates were higher among Jews than Arab
      and among men than women. There were no significant change in the mortality rates
      and rate ratios. CONCLUSIONS: Our findings demonstrate marked ethnic differences
      in RCC in Israel. The lower incidence among Arabs stands in contrast to the
      higher prevalence of potential risk factors for RCC in this population group.
      Genetic factors, diet and other lifestyle factors could play protective roles.

PMID- 20129842
TI  - Discretization error analysis and adaptive meshing algorithms for fluorescence
      diffuse optical tomography: part I.
AB  - For imaging problems in which numerical solutions need to be computed for both
      the inverse and the underlying forward problems, discretization can be a major
      factor that determines the accuracy of imaging. In this work, we analyze the
      effect of discretization on the accuracy of fluorescence diffuse optical
      tomography. We model the forward problem by a pair of diffusion equations at the
      excitation and emission wavelengths and consider a finite element discretization
      method for the numerical solution of the forward problem. For the inverse
      problem, we use an optimization framework which allows incorporation of a priori
      information in the form of zeroth- and first-order Tikhonov regularization terms.
      Next, we convert the inverse problem into a variational problem and use Galerkin
      projection to discretize the inverse problem. Following the discretization, we
      analyze the error in reconstructed images due to the discretization of the
      forward and inverse problems and present two theorems which point out the factors
      that may lead to high error such as the mutual dependence of the forward and
      inverse problems, the number of sources and detectors, their configuration and
      their positions with respect to fluorophore concentration, and the formulation of
      the inverse problem. Finally, we demonstrate the results and implications of our
      error analysis by numerical experiments. In the second part of the paper, we
      apply our results to design novel adaptive discretization algorithms.

PMID- 20129843
TI  - Automatic segmentation of rotational x-ray images for anatomic intra-procedural
      surface generation in atrial fibrillation ablation procedures.
AB  - Since the introduction of 3-D rotational X-ray imaging, protocols for 3-D
      rotational coronary artery imaging have become widely available in routine
      clinical practice. Intra-procedural cardiac imaging in a computed tomography (CT)
      like fashion has been particularly compelling due to the reduction of clinical
      overhead and ability to characterize anatomy at the time of intervention. We
      previously introduced a clinically feasible approach for imaging the left atrium
      and pulmonary veins (LAPVs) with short contrast bolus injections and scan times
      of approximately 4 -10 s. The resulting data have sufficient image quality for
      intra-procedural use during electro-anatomic mapping (EAM) and interventional
      guidance in atrial fibrillation (AF) ablation procedures. In this paper, we
      present a novel technique to intra-procedural surface generation which integrates
      fully-automated segmentation of the LAPVs for guidance in AF ablation
      interventions. Contrast-enhanced rotational X-ray angiography (3-D RA)
      acquisitions in combination with filtered-back-projection-based reconstruction
      allows for volumetric interrogation of LAPV anatomy in near-real-time. An
      automatic model-based segmentation algorithm allows for fast and accurate LAPV
      mesh generation despite the challenges posed by image quality; relative to pre
      procedural cardiac CT/MR, 3-D RA images suffer from more artifacts and reduced
      signal-to-noise. We validate our integrated method by comparing 1) automatic and
      manual segmentations of intra-procedural 3-D RA data, 2) automatic segmentations
      of intra-procedural 3-D RA and pre-procedural CT/MR data, and 3) intra-procedural
      EAM point cloud data with automatic segmentations of 3-D RA and CT/MR data. Our
      validation results for automatically segmented intra-procedural 3-D RA data show
      average segmentation errors of 1) approximately 1.3 mm compared with manual 3-D
      RA segmentations 2) approximately 2.3 mm compared with automatic segmentation of
      pre-procedural CT/MR data and 3) approximately 2.1 mm compared with registered
      intra-procedural EAM point clouds. The overall experiments indicate that LAPV
      surfaces can be automatically segmented intra-procedurally from 3-D RA data with
      comparable quality relative to meshes derived from pre-procedural CT/MR.

PMID- 20129844
TI  - Image-guided intraoperative cortical deformation recovery using game theory:
      application to neocortical epilepsy surgery.
AB  - During neurosurgery, nonrigid brain deformation prevents preoperatively-acquired
      images from accurately depicting the intraoperative brain. Stereo vision systems
      can be used to track intraoperative cortical surface deformation and update
      preoperative brain images in conjunction with a biomechanical model. However,
      these stereo systems are often plagued with calibration error, which can corrupt
      the deformation estimation. In order to decouple the effects of camera
      calibration from the surface deformation estimation, a framework that can solve
      for disparate and often competing variables is needed. Game theory, which was
      developed to handle decision making in this type of competitive environment, has
      been applied to various fields from economics to biology. In this paper, game
      theory is applied to cortical surface tracking during neocortical epilepsy
      surgery and used to infer information about the physical processes of brain
      surface deformation and image acquisition. The method is successfully applied to
      eight in vivo cases, resulting in an 81% decrease in mean surface displacement
      error. This includes a case in which some of the initial camera calibration
      parameters had errors of 70%. Additionally, the advantages of using a game
      theoretic approach in neocortical epilepsy surgery are clearly demonstrated in
      its robustness to initial conditions.

PMID- 20129845
TI  - Ideal AFROC and FROC observers.
AB  - Detection of multiple lesions in images is a medically important task and free
      response receiver operating characteristic (FROC) analyses and its variants, such
      as alternative FROC (AFROC) analyses, are commonly used to quantify performance
      in such tasks. However, ideal observers that optimize FROC or AFROC performance
      metrics have not yet been formulated in the general case. If available, such
      ideal observers may turn out to be valuable for imaging system optimization and
      in the design of computer aided diagnosis techniques for lesion detection in
      medical images. In this paper, we derive ideal AFROC and FROC observers. They are
      ideal in that they maximize, amongst all decision strategies, the area, or any
      partial area, under the associated AFROC or FROC curve. Calculation of observer
      performance for these ideal observers is computationally quite complex. We can
      reduce this complexity by considering forms of these observers that use false
      positive reports derived from signal-absent images only. We also consider a Bayes
      risk analysis for the multiple-signal detection task with an appropriate
      definition of costs. A general decision strategy that minimizes Bayes risk is
      derived. With particular cost constraints, this general decision strategy reduces
      to the decision strategy associated with the ideal AFROC or FROC observer.

PMID- 20129846
TI  - The LoG characteristic scale: a consistent measurement of lung nodule size in CT
      imaging.
AB  - Nodule growth as observed in computed tomography (CT) scans acquired at different
      times is the primary feature to malignancy of indeterminate small lung nodules.
      In this paper, we propose the estimation of nodule size through a scale-space
      representation which needs no segmentation and has high intra- and inter-operator
      reproducibility. Lung nodules usually appear in CT images as blob-like patterns
      and can be analyzed in the scale-space by Laplacian of Gaussian ( LoG ) kernels.
      For each nodular pattern the LoG scale-space signature was computed and the
      related characteristic scale adopted as measurement of nodule size. Both in vitro
      and in vivo validation of LoG characteristic scale were carried out. In vitro
      validation was done by 40 nondeformable phantoms and 10 deformable phantoms. A
      close relationship between the characteristic scale and the equivalent diameter,
      i.e., the diameter of the sphere having the same volume of nodules, (Pearson
      correlation coefficient was 0.99) and, for nodules undergoing little deformations
      (obtained at constant volume), small variability of the characteristic scale was
      observed. The in vivo validation was performed on low and standard-dose CT scans
      collected from the ITALUNG screening trial (86 nodules) and from the LIDC public
      data set (89 solid nodules and 40 part-solid nodules or ground-glass opacities).
      The Pearson correlation coefficient between characteristic scale and equivalent
      diameter was 0.83-0.93 for ITALUNG and 0.68-0.83 for LIDC data set. Intra- and
      inter-operator reproducibility of characteristic scale was excellent: on a set of
      40 lung nodules of ITALUNG data, two radiologists produced identical results in
      repeated measurements. The scan-rescan variability of the characteristic scale
      was also investigated on 86 two-year-stable solid lung nodules (each one
      observed, on average, in four CT scans) identified in the ITALUNG screening
      trial: a coefficient of repeatability of about 0.9 mm was observed. Experimental
      evidence supports the clinical use of the LoG characteristic scale to measure
      nodule size in CT imaging.

PMID- 20129847
TI  - Imaging electric properties of biological tissues by RF field mapping in MRI.
AB  - The electric properties (EPs) of biological tissue, i.e., the electric
      conductivity and permittivity, can provide important information in the diagnosis
      of various diseases. The EPs also play an important role in specific absorption
      rate calculation, a major concern in high-field MRI, as well as in nonmedical
      areas such as wireless telecommunications. The high-field MRI system is
      accompanied by significant wave propagation effects, and the RF radiation is
      dependent on the EPs of biological tissue. On the basis of the measurement of the
      active transverse magnetic component of the applied RF field (known as B(1)
      mapping technique), we propose a dual-excitation algorithm, which uses two sets
      of measured B(1) data to noninvasively reconstruct the EPs of biological tissues.
      The finite-element method was utilized in 3-D modeling and B(1) field
      calculation. A series of computer simulations were conducted to evaluate the
      feasibility and performance of the proposed method on a 3-D head model within a
      TEM coil and a birdcage coil. Using a TEM coil, when noise free, the
      reconstructed EP distribution of tissues in the brain has relative errors of 12%
      28% and correlated coefficients of greater than 0.91. Compared with other B(1)
      mapping-based reconstruction algorithms, our approach provides superior
      performance without the need for iterative computations. The present simulation
      results suggest that good reconstruction of EPs from B1 mapping can be achieved.

PMID- 20129848
TI  - An MRI receiver coil produced by inkjet printing directly on to a flexible
      substrate.
AB  - Inkjet printing has been used to produce resonant radio frequency coils that are
      comparable to those produced by conventional printed circuit board (PCB) methods.
      The coils, which consist of a conductive loop and in-series capacitors, form part
      of a receiver circuit that is used for magnetic resonance imaging (MRI). The
      resonant circuit is selective at the predetermined frequency of 400 MHz. The
      required electrical components (resistor, capacitor, and inductor) were produced
      by inkjet printing, with scaling experiments for resistor and capacitor performed
      before the complete loops with integrated capacitors were printed. Numerical
      simulation was used to determine the required values for the components. The
      inkjet printed circuit was combined with a small tuning and matching board before
      being connected to a network analyzer and the MRI hardware. With a matching of -
      38 dB at 400 MHz the achieved results were comparable to those from standard PCB
      techniques. The performance of the inkjet printed component as a receiver device
      for nuclear magnetic resonance and MRI was verified by imaging reference phantoms
      and a whole kiwifruit; it compares favorably to standard MRI devices. Inkjet
      printing can, therefore, be considered a feasible technique for producing MRI
      receiver circuits on flexible substrates.

PMID- 20129849
TI  - Automated and interactive lesion detection and segmentation in uterine cervix
      images.
AB  - This paper presents a procedure for automatic extraction and segmentation of a
      class-specific object (or region) by learning class-specific boundaries. We
      describe and evaluate the method with a specific focus on the detection of lesion
      regions in uterine cervix images. The watershed segmentation map of the input
      image is modeled using a Markov random field (MRF) in which watershed regions
      correspond to binary random variables indicating whether the region is part of
      the lesion tissue or not. The local pairwise factors on the arcs of the watershed
      map indicate whether the arc is part of the object boundary. The factors are
      based on supervised learning of a visual word distribution. The final lesion
      region segmentation is obtained using a loopy belief propagation applied to the
      watershed arc-level MRF. Experimental results on real data show state-of-the-art
      segmentation results on this very challenging task that, if necessary, can be
      interactively enhanced.

PMID- 20129850
TI  - Multiscale AM-FM methods for diabetic retinopathy lesion detection.
AB  - In this paper, we propose the use of multiscale amplitude-modulation-frequency
      modulation (AM-FM) methods for discriminating between normal and pathological
      retinal images. The method presented in this paper is tested using standard
      images from the early treatment diabetic retinopathy study. We use 120 regions of
      40 x 40 pixels containing four types of lesions commonly associated with diabetic
      retinopathy (DR) and two types of normal retinal regions that were manually
      selected by a trained analyst. The region types included microaneurysms,
      exudates, neovascularization on the retina, hemorrhages, normal retinal
      background, and normal vessels patterns. The cumulative distribution functions of
      the instantaneous amplitude, the instantaneous frequency magnitude, and the
      relative instantaneous frequency angle from multiple scales are used as texture
      feature vectors. We use distance metrics between the extracted feature vectors to
      measure interstructure similarity. Our results demonstrate a statistical
      differentiation of normal retinal structures and pathological lesions based on AM
      FM features. We further demonstrate our AM-FM methodology by applying it to
      classification of retinal images from the MESSIDOR database. Overall, the
      proposed methodology shows significant capability for use in automatic DR
      screening.

PMID- 20129851
TI  - Classification of benign and malignant breast tumors by 2-d analysis based on
      contour description and scatterer characterization.
AB  - Ultrasound B-mode scanning based on the echo intensity has become an important
      clinical tool for routine breast screening. The efficacy of the Nakagami
      parametric image based on the distribution of the backscattered signals for
      quantifying properties of breast tissue was recently evaluated. The B-mode and
      Nakagami images reflect different physical characteristic of breast tumors: the
      former describes the contour features, and the latter reflects the scatterer
      arrangement inside a tumor. The functional complementation of these two images
      encouraged us to propose a novel method of 2-D analysis based on describing the
      contour using the B-mode image and the scatterer properties using the Nakagami
      image, which may provide useful clues for classifying benign and malignant
      tumors. To validate this concept, raw data were acquired from 60 clinical cases,
      and five contour feature parameters (tumor circularity, standard deviation of the
      normalized radial length, area ratio, roughness index, and standard deviation of
      the shortest distance) and the Nakagami parameters of benign and malignant tumors
      were calculated. The receiver operating characteristic curve and fuzzy c-means
      clustering were used to evaluate the performances of combining the parameters in
      classifying tumors. The clinical results demonstrated the presence of a tradeoff
      between the sensitivity and specificity when either using a single parameter or
      combining two contour parameters to discriminate between benign and malignant
      cases. However, combining the contour parameters and the Nakagami parameter
      produces sensitivity and specificity that simultaneously exceed 80%, which means
      that the functional complementation from the B-scan and the Nakagami image indeed
      enhances the performance in diagnosing breast tumors.

PMID- 20129852
TI  - An analytic framework for the evaluation of coil configurations for parallel
      transmission MRI with subsampled cartesian excitation k-space.
AB  - The use of multiple independent simultaneous radio-frequency (RF) transmitters
      and coils, known as parallel transmission, has the potential to make
      multidimensional excitation applicable to a wide range of magnetic resonance
      imaging applications. The sensitivity profile of the RF coils in a parallel
      transmission system determines the performance of the system. We present a
      theoretical framework, allowing the evaluation of the performance of a coil array
      for parallel transmission. We show through theoretical analysis and Monte Carlo
      simulation that the proposed framework predicts the fidelity of excitation that
      can be achieved by a given coil configuration in the presence of noise in the
      measured coil sensitivity profiles. We evaluate the fidelity of excitation
      achieved by four candidate coil configurations for a four-channel parallel
      transmission system with noisy coil sensitivity estimates. Theoretical results
      are confirmed with Monte Carlo simulation. The results give insight into the
      design of coil configurations for parallel transmission. In particular, optimal
      fidelity of excitation for subsampled Cartesian excitation k -space is achieved
      with a coil sensitivity profile having uniform amplitude and increasing linear
      phase for each channel. Such sensitivity profiles may be achieved with twisted
      birdcage coil designs.

PMID- 20129853
TI  - Random subspace ensembles for FMRI classification.
AB  - Classification of brain images obtained through functional magnetic resonance
      imaging (fMRI) poses a serious challenge to pattern recognition and machine
      learning due to the extremely large feature-to-instance ratio. This calls for
      revision and adaptation of the current state-of-the-art classification methods.
      We investigate the suitability of the random subspace (RS) ensemble method for
      fMRI classification. RS samples from the original feature set and builds one
      (base) classifier on each subset. The ensemble assigns a class label by either
      majority voting or averaging of output probabilities. Looking for guidelines for
      setting the two parameters of the method-ensemble size and feature sample size-we
      introduce three criteria calculated through these parameters: usability of the
      selected feature sets, coverage of the set of "important" features, and feature
      set diversity. Optimized together, these criteria work toward producing accurate
      and diverse individual classifiers. RS was tested on three fMRI datasets from
      single-subject experiments: the Haxby data (Haxby, 2001.) and two datasets
      collected in-house. We found that RS with support vector machines (SVM) as the
      base classifier outperformed single classifiers as well as some of the most
      widely used classifier ensembles such as bagging, AdaBoost, random forest, and
      rotation forest. The closest rivals were the single SVM and bagging of SVM
      classifiers. We use kappa-error diagrams to understand the success of RS.

PMID- 20129854
TI  - Regularized interpolation for noisy images.
AB  - Interpolation is the means by which a continuously defined model is fit to
      discrete data samples. When the data samples are exempt of noise, it seems
      desirable to build the model by fitting them exactly. In medical imaging, where
      quality is of paramount importance, this ideal situation unfortunately does not
      occur. In this paper, we propose a scheme that improves on the quality by
      specifying a tradeoff between fidelity to the data and robustness to the noise.
      We resort to variational principles, which allow us to impose smoothness
      constraints on the model for tackling noisy data. Based on shift-, rotation-, and
      scale-invariant requirements on the model, we show that the L(p)-norm of an
      appropriate vector derivative is the most suitable choice of regularization for
      this purpose. In addition to Tikhonov-like quadratic regularization, this
      includes edge-preserving total-variation-like (TV) regularization. We give
      algorithms to recover the continuously defined model from noisy samples and also
      provide a data-driven scheme to determine the optimal amount of regularization.
      We validate our method with numerical examples where we demonstrate its
      superiority over an exact fit as well as the benefit of TV-like nonquadratic
      regularization over Tikhonov-like quadratic regularization.

PMID- 20129855
TI  - Quantitative analysis of pulmonary emphysema using local binary patterns.
AB  - We aim at improving quantitative measures of emphysema in computed tomography
      (CT) images of the lungs. Current standard measures, such as the relative area of
      emphysema (RA), rely on a single intensity threshold on individual pixels, thus
      ignoring any interrelations between pixels. Texture analysis allows for a much
      richer representation that also takes the local structure around pixels into
      account. This paper presents a texture classification-based system for emphysema
      quantification in CT images. Measures of emphysema severity are obtained by
      fusing pixel posterior probabilities output by a classifier. Local binary
      patterns (LBP) are used as texture features, and joint LBP and intensity
      histograms are used for characterizing regions of interest (ROIs). Classification
      is then performed using a k nearest neighbor classifier with a histogram
      dissimilarity measure as distance. A 95.2% classification accuracy was achieved
      on a set of 168 manually annotated ROIs, comprising the three classes: normal
      tissue, centrilobular emphysema, and paraseptal emphysema. The measured emphysema
      severity was in good agreement with a pulmonary function test (PFT) achieving
      correlation coefficients of up to |r| = 0.79 in 39 subjects. The results were
      compared to RA and to a Gaussian filter bank, and the texture-based measures
      correlated significantly better with PFT than did RA.

PMID- 20129856
TI  - Optical-flow-based B-mode elastography: application in the hypertensive rat
      carotid.
AB  - Background-Ultrasound elastography is now used worldwide in tissue
      characterization. The primary premises of elastography are that speckle
      kinematics reproduces underlying tissue kinematics and that tissue motion can be
      inferred from speckle tracking. This implicitly assumes that speckle pattern is a
      material property that can be tracked with respect to time and space. It is then
      convenient to express the motion of such a material property in terms of total
      derivative, also known as optical flow (OF) equations. Aims-The present paper
      introduces a new iterative OF-based elastography (OFBE) method devoted to B-mode
      data. The first OFBE iteration computes axial and lateral displacement fields.
      Such displacement fields are used for data rigid registration, prior to the
      second OFBE iteration which computes the 2-D strain tensor. Methods-The OFBE
      method was validated in the common carotid artery of rat hypertension models. The
      effect of aging on carotid stiffness was investigated in female recombinant
      inbred rats (RI-17, (n=2)) in the first experiment. The outcomes of low/high-salt
      diets were examined in young male Dahl salt-sensitive rats (SS, n=6; SM12, n=6;
      SM9, n=6) in the second experiment. Results-Good concordance was observed between
      left and right carotid axial strain measurements with 11.4% relative error,
      whereas 4.6% relative error occurred between diastolic and systolic axial strain
      measurements. Old (80 and 85 weeks) RI-17 carotids were determined to be twice as
      stiff with 5.70 +/- 0.97% (strain+/-std) as young carotids (30 and 34 weeks) with
      13.26 +/- 2.73%, p < 0.001. Carotid axial strain measurement also indicated that
      salt diets had a significant impact on SS (p=0.008) and SM12 (p < 0.001) but not
      on SM9 (p=0.881) rats.

PMID- 20129857
TI  - On the weight convergence of Elman networks.
AB  - An Elman network (EN) can be viewed as a feedforward (FF) neural network with an
      additional set of inputs from the context layer (feedback from the hidden layer).
      Therefore, instead of the offline backpropagation-through-time (BPTT) algorithm,
      a standard online (real-time) backpropagation (BP) algorithm, usually called
      Elman BP (EBP), can be applied for EN training for discrete-time sequence
      predictions. However, the standard BP training algorithm is not the most suitable
      for ENs. A low learning rate can improve the training of ENs but can also result
      in very slow convergence speeds and poor generalization performance, whereas a
      high learning rate can lead to unstable training in terms of weight divergence.
      Therefore, an optimal or suboptimal tradeoff between training speed and weight
      convergence with good generalization capability is desired for ENs. This paper
      develops a robust extended EBP (eEBP) training algorithm for ENs with a new
      adaptive dead zone scheme based on eEBP training concepts. The adaptive learning
      rate and adaptive dead zone optimize the training of ENs for each individual
      output and improve the generalization performance of the eEBP training. In
      particular, for the proposed eEBP training algorithm, convergence of the ENs'
      weights with the adaptive dead zone estimates is proven in the sense of Lyapunov
      functions. Computer simulations are carried out to demonstrate the improved
      performance of eEBP for discrete-time sequence predictions.

PMID- 20129858
TI  - PSECMAC intelligent insulin schedule for diabetic blood glucose management under
      nonmeal announcement.
AB  - Therapeutically, the closed-loop blood glucose-insulin regulation paradigm via a
      controllable insulin pump offers a potential solution to the management of
      diabetes. However, the development of such a closed-loop regulatory system to
      date has been hampered by two main issues: 1) the limited knowledge on the
      complex human physiological process of glucose-insulin metabolism that prevents a
      precise modeling of the biological blood glucose control loop; and 2) the vast
      metabolic biodiversity of the diabetic population due to varying exogneous and
      endogenous disturbances such as food intake, exercise, stress, and hormonal
      factors, etc. In addition, current attempts of closed-loop glucose regulatory
      techniques generally require some form of prior meal announcement and this
      constitutes a severe limitation to the applicability of such systems. In this
      paper, we present a novel intelligent insulin schedule based on the pseudo self
      evolving cerebellar model articulation controller (PSECMAC) associative learning
      memory model that emulates the healthy human insulin response to food ingestion.
      The proposed PSECMAC intelligent insulin schedule requires no prior meal
      announcement and delivers the necessary insulin dosage based only on the observed
      blood glucose fluctuations. Using a simulated healthy subject, the proposed
      PSECMAC insulin schedule is demonstrated to be able to accurately capture the
      complex human glucose-insulin dynamics and robustly addresses the intraperson
      metabolic variability. Subsequently, the PSECMAC intelligent insulin schedule is
      employed on a group of type-1 diabetic patients to regulate their impaired blood
      glucose levels. Preliminary simulation results are highly encouraging. The work
      reported in this paper represents a major paradigm shift in the management of
      diabetes where patient compliance is poor and the need for prior meal
      announcement under current treatment regimes poses a significant challenge to an
      active lifestyle.

PMID- 20129859
TI  - Simple camera calibration from a single image using five points on two orthogonal
      1-D objects.
AB  - We propose a simple and practical calibration technique that effectively
      estimates camera parameters from just five points on two orthogonal 1-D objects,
      each which has three collinear points, one of which is shared. We derive the
      basic equations needed to realize camera calibration from just five points
      observed on a single image that captures the objects. We describe a new camera
      calibration algorithm that estimates the camera parameters based on the basic
      equations and optimizes them by the bundle adjustment technique. Our method is
      validated by both computer simulated data and real images. The results show that
      the camera parameters yielded by our method are close to those yielded by
      existing methods. The tests demonstrate that our method is both effective and
      practical.

PMID- 20129860
TI  - Maximum a posteriori video super-resolution using a new multichannel image prior.
AB  - Super-resolution (SR) is the term used to define the process of estimating a high
      resolution (HR) image or a set of HR images from a set of low-resolution (LR)
      observations. In this paper we propose a class of SR algorithms based on the
      maximum a posteriori (MAP) framework. These algorithms utilize a new multichannel
      image prior model, along with the state-of-the-art single channel image prior and
      observation models. A hierarchical (two-level) Gaussian nonstationary version of
      the multichannel prior is also defined and utilized within the same framework.
      Numerical experiments comparing the proposed algorithms among themselves and with
      other algorithms in the literature, demonstrate the advantages of the adopted
      multichannel approach.

PMID- 20129861
TI  - Study of subjective and objective quality assessment of video.
AB  - We present the results of a recent large-scale subjective study of video quality
      on a collection of videos distorted by a variety of application-relevant
      processes. Methods to assess the visual quality of digital videos as perceived by
      human observers are becoming increasingly important, due to the large number of
      applications that target humans as the end users of video. Owing to the many
      approaches to video quality assessment (VQA) that are being developed, there is a
      need for a diverse independent public database of distorted videos and subjective
      scores that is freely available. The resulting Laboratory for Image and Video
      Engineering (LIVE) Video Quality Database contains 150 distorted videos (obtained
      from ten uncompressed reference videos of natural scenes) that were created using
      four different commonly encountered distortion types. Each video was assessed by
      38 human subjects, and the difference mean opinion scores (DMOS) were recorded.
      We also evaluated the performance of several state-of-the-art, publicly available
      full-reference VQA algorithms on the new database. A statistical evaluation of
      the relative performance of these algorithms is also presented. The database has
      a dedicated web presence that will be maintained as long as it remains relevant
      and the data is available online.

PMID- 20129862
TI  - Texture classification by modeling joint distributions of local patterns with
      gaussian mixtures.
AB  - Texture classification generally requires the analysis of patterns in local pixel
      neighborhoods. Statistically, the underlying processes are comprehensively
      described by their joint probability density functions (jPDFs). Even for small
      neighborhoods, however, stable estimation of jPDFs by joint histograms (jHSTs) is
      often infeasible, since the number of entries in the jHST exceeds by far the
      number of pixels in a typical texture region. Moreover, evaluation of distance
      functions between jHSTs is often computationally prohibitive. Practically, the
      number of entries in a jHST is therefore reduced by considering only two-pixel
      patterns, leading to 2D-jHSTs known as cooccurrence matrices, or by quantization
      of the gray levels in local patterns to only two gray levels, yielding local
      binary patterns (LBPs). Both approaches result in a loss of information. We
      introduce here a framework for supervised texture classification which reduces or
      avoids this information loss. Local texture neighborhoods are first filtered by a
      filter bank. Without further quantization, the jPDF of the filter responses is
      then described parametrically by gaussian mixture models (GMMs). We show that the
      parameters of the GMMs can be reliably estimated from small image regions.
      Moreover, distances between the thus modelled jPDFs of different texture patterns
      can be computed efficiently in closed form from their model parameters. We
      furthermore extend this texture descriptor to achieve full invariance to
      rotation. We evaluate the framework for different filter banks on the Brodatz
      texture set. We first show that combining the LBP difference filters with the GMM
      based density estimator outperforms the classical LBP approach and its codebook
      extensions. When replacing these-rather elementary-difference filters by the
      wavelet frame transform (WFT), the performance of the framework on all 111
      Brodatz textures exceeds the one obtained more recently by spin image and RIFT
      descriptors by Lazebnik et al.

PMID- 20129864
TI  - Image inpainting by patch propagation using patch sparsity.
AB  - This paper introduces a novel examplar-based inpainting algorithm through
      investigating the sparsity of natural image patches. Two novel concepts of
      sparsity at the patch level are proposed for modeling the patch priority and
      patch representation, which are two crucial steps for patch propagation in the
      examplar-based inpainting approach. First, patch structure sparsity is designed
      to measure the confidence of a patch located at the image structure (e.g., the
      edge or corner) by the sparseness of its nonzero similarities to the neighboring
      patches. The patch with larger structure sparsity will be assigned higher
      priority for further inpainting. Second, it is assumed that the patch to be
      filled can be represented by the sparse linear combination of candidate patches
      under the local patch consistency constraint in a framework of sparse
      representation. Compared with the traditional examplar-based inpainting approach,
      structure sparsity enables better discrimination of structure and texture, and
      the patch sparse representation forces the newly inpainted regions to be sharp
      and consistent with the surrounding textures. Experiments on synthetic and
      natural images show the advantages of the proposed approach.

PMID- 20129863
TI  - Atlas generation for subcortical and ventricular structures with its applications
      in shape analysis.
AB  - Atlas-driven morphometric analysis has received great attention for studying
      anatomical shape variation across clinical populations in neuroimaging research
      as it provides a local coordinate representation for understanding the family of
      anatomic observations. We present a procedure for generating atlas of subcortical
      and ventricular structures, including amygdala, hippocampus, caudate, putamen,
      globus pallidus, thalamus, and lateral ventricles, using the large deformation
      diffeomorphic metric atlas generation algorithm. The atlas was built based on
      manually labeled volumes of 41 subjects randomly selected from the database of
      Open Access Series of Imaging Studies (OASIS, 10 young adults, 10 middle-age
      adults, 10 healthy elders, and 11 patients with dementia). We show that the
      estimated atlas is representative of the population in terms of its metric
      distance to each individual subject in the population. In the application of
      detecting shape variations, using the estimated atlas may potentially increase
      statistical power in identifying group shape difference when comparing with using
      a single subject atlas. In shape-based classification, the metric distances
      between subjects and each of within-class estimated atlases construct a shape
      feature space, which allows for performing a variety of classification algorithms
      to distinguish anatomies.

PMID- 20129865
TI  - An object-based visual attention model for robotic applications.
AB  - By extending integrated competition hypothesis, this paper presents an object
      based visual attention model, which selects one object of interest using low
      dimensional features, resulting that visual perception starts from a fast
      attentional selection procedure. The proposed attention model involves seven
      modules: learning of object representations stored in a long-term memory (LTM),
      preattentive processing, top-down biasing, bottom-up competition, mediation
      between top-down and bottom-up ways, generation of saliency maps, and perceptual
      completion processing. It works in two phases: learning phase and attending
      phase. In the learning phase, the corresponding object representation is trained
      statistically when one object is attended. A dual-coding object representation
      consisting of local and global codings is proposed. Intensity, color, and
      orientation features are used to build the local coding, and a contour feature is
      employed to constitute the global coding. In the attending phase, the model
      preattentively segments the visual field into discrete proto-objects using
      Gestalt rules at first. If a task-specific object is given, the model recalls the
      corresponding representation from LTM and deduces the task-relevant feature(s) to
      evaluate top-down biases. The mediation between automatic bottom-up competition
      and conscious top-down biasing is then performed to yield a location-based
      saliency map. By combination of location-based saliency within each proto-object,
      the proto-object-based saliency is evaluated. The most salient proto-object is
      selected for attention, and it is finally put into the perceptual completion
      processing module to yield a complete object region. This model has been applied
      into distinct tasks of robots: detection of task-specific stationary and moving
      objects. Experimental results under different conditions are shown to validate
      this model.

PMID- 20129866
TI  - Automatic face segmentation and facial landmark detection in range images.
AB  - We present a methodology for face segmentation and facial landmark detection in
      range images. Our goal was to develop an automatic process to be embedded in a
      face recognition system using only depth information as input. To this end, our
      segmentation approach combines edge detection, region clustering, and shape
      analysis to extract the face region, and our landmark detection approach combines
      surface curvature information and depth relief curves to find the nose and eye
      landmarks. The experiments were performed using the two available versions of the
      Face Recognition Grand Challenge database and the BU-3DFE database, in order to
      validate our proposed methodology and its advantages for 3-D face recognition
      purposes. We present an analysis regarding the accuracy of our segmentation and
      landmark detection approaches. Our results were better compared to state-of-the
      art works published in the literature. We also performed an evaluation regarding
      the influence of the segmentation process in our 3-D face recognition system and
      analyzed the improvements obtained when applying landmark-based techniques to
      deal with facial expressions.

PMID- 20129867
TI  - Integrating information from vision and touch: a neural network modeling study.
AB  - Perception of external events often depends on integrating different sensory
      information. Many studies show strong evidence for visual-tactile integrations.
      Understanding how visual and tactile information are merged together is still a
      challenging problem. Here, a neural network model was used to investigate the
      mechanisms underlying visual-tactile interactions. It includes two unimodal areas
      (visual and tactile, respectively), sending feedforward connections into a
      downstream bimodal area. The unimodal areas influence each other via two synaptic
      mechanisms: feedback synapses from the bimodal area and direct reciprocal
      connections. The network reproduces a variety of visual-tactile interactions: 1)
      detection of faint tactile stimuli is facilitated by concomitant visual input; 2)
      tactile spatial resolution is improved by visual information; 3) cross-modal
      advantages are maximum when poor unisensory information is available (inverse
      effectiveness); and 4) conflict situations are resolved based on the more
      reliable sensory cue. The model identifies distinct roles for the feedback and
      direct synapses: the first are fundamental to improve detection of low-intensity
      tactile stimuli in cross-modal stimulation, and the second are mostly implicated
      in visual enhancement of tactile spatial localization and resolution. A better
      comprehension of how vision and touch interact in the neural system may
      contribute to physiological knowledge, clinical practice, and technological
      applications.

PMID- 20129868
TI  - Web-services-based resource discovery model and service deployment on
      HealthGrids.
AB  - HealthGrids represent the next generation of advanced healthcare IT and hold the
      promise to untangle complex healthcare-data problems by integrating health
      information systems and healthcare entities. Healthcare could benefit from a new
      delivery approach using HealthGrids to better meet the biomedical and health
      related needs. Specialized services are needed to provide unified discovery of
      and ubiquitous access to available HealthGrid resources. The different types of
      services available on HealthGrids are classified into two levels, the operational
      level services and the management-level services. This paper takes a fresh
      approach to address the problems of resource discovery in HealthGrids based on
      Web services (WS) and WS technologies and proposes a WS-based resource discovery
      model.

PMID- 20129869
TI  - Numerical methods and workstation for the quantitative analysis of real-time
      myocardial contrast echocardiography.
AB  - Using the quantitative analysis of real-time myocardial contrast echocardiography
      (RT MCE), clinicians can assess the myocardial perfusion of patients,
      noninvasively and accurately. We designed a workstation to assist clinicians to
      automatically implement the accurate analysis of RT MCE. The workstation can
      compute some hemodynamic parameters of myocardial microcirculation, e.g.,
      myocardial blood flow, myocardial blood flow mean velocity, and myocardial blood
      volume. Our new methods involved in the quantitative analysis of RT MCE are
      summarized as follows. 1) A novel orthogonal array optimization (OAO) technique
      was proposed and used to estimate the unknown parameters of the nonlinear model
      to guarantee numerical stability. 2) Brox's coarse-to-fine warping optical flow
      technique was employed to automatically track the region of interest located
      inside the myocardial area to ensure the accuracy of the quantitative analysis.
      Finally, we illustrate some examples of clinical studies to indicate the
      effectiveness of the system and the reliability of the methods.

PMID- 20129870
TI  - A Cusum-based multilevel alerting method for physiological monitoring.
AB  - Alerting systems used by current physiological monitors are designed to detect
      changes in the levels of vital signs, but they tend to be very sensitive to
      artifacts. This paper proposes a method to detect changes in the direction of
      trend and generate multilevel alerts according to the statistical significance of
      the detection. One-point-ahead signal predictions are calculated by averaging the
      historical data with the weights decreasing in the past. The two-sided cumulative
      sums (Cusum) of the prediction errors are tested against multiple thresholds to
      detect change points with two levels of certainty. The temporal shapes of the
      detected changes are analyzed using heuristics to determine whether to trigger an
      alert. The method was tested offline using 20 cases collected during surgery at a
      local hospital. The detection results were evaluated by two experienced
      anesthesiologists. The direction of trend was correctly detected in 90.2% of the
      annotated changes for end-tidal carbon dioxide, 89.4% for expiratory minute
      volume, 91.8% for peak airway pressure, and 95.4% for noninvasive blood pressure.
      The certainty levels of the true-positive alerts estimated by the algorithm have
      a high ratio of agreement with the anesthesiologists' evaluations.

PMID- 20129871
TI  - A multiresolution method for tagline detection and indexing.
AB  - Tagline detection and indexing are challenging tasks due to complicated
      anatomical properties and imaging noise. In this paper, we will address the
      following two important issues in tagline detection: 1) an automatic method
      independent from imaging approaches with improved robustness and accuracy and 2)
      tagline indexing that matches taglines in task and reference images for
      postprocessing. Our method consists of two steps: First, a wavelet decomposition
      is performed on a tagged magnetic resonance (tMR) image. Subband correlation is
      used to dampen anatomical boundaries but enhance taglines. A tagline map is
      created by segmenting a reconstructed image using pseudowavelet reconstruction.
      Next, tagline pixels are grouped into clusters and isolated small line segments
      are eliminated. A snake method is then used to index and recover broken taglines.
      Our method has been validated with 320 tMR tongue images. Measurement of tagline
      accuracy was performed by computing tag pixel displacement. Without assumptions
      on tagline models, it detects taglines automatically. Comparison studies were
      conducted against the harmonic phase method. Our experiments resulted in a p
      value of 1E-6 with one-way ANOVA, which indicates a significant improvement in
      accuracy and robustness.

PMID- 20129872
TI  - Predicting the risk of low-fetal birth weight from cardiotocographic signals
      using ANBLIR system with deterministic annealing and epsilon-insensitive
      learning.
AB  - Cardiotocography (CTG) is a biophysical method of fetal condition assessment
      based mainly on recording and automated analysis of fetal heart activity. The
      computerized fetal monitoring systems provide the quantitative description of the
      CTG signals, but the effective conclusion generation methods for decision process
      support are still needed. Assessment of the fetal state can be verified only
      after delivery using the fetal (newborn) outcome data. One of the most important
      features defining the abnormal fetal outcome is low birth weight. This paper
      describes an application of the artificial neural network based on logical
      interpretation of fuzzy if-then rules neurofuzzy system to evaluate the risk of
      low-fetal birth weight using the quantitative description of CTG signals. We
      applied different learning procedures integrating least squares method,
      deterministic annealing (DA) algorithm, and epsilon-insensitive learning, as well
      as various methods of input dataset modification. The performance was evaluated
      with the number of correctly classified cases (CC) expressed as the percentage of
      the testing set size, and with overall index (OI) being the function of
      predictive indexes. The best classification efficiency (CC = 97.5% and OI =
      82.7%), was achieved for integrated DA with epsilon-insensitive learning and
      dataset comprising of the CTG traces recorded as earliest for a given patient.
      The obtained results confirm efficiency for supporting the fetal outcome
      prediction using the proposed methods.

PMID- 20129873
TI  - Comparison of current-use pesticide and other toxicant urinary metabolite levels
      among pregnant women in the CHAMACOS cohort and NHANES.
AB  - BACKGROUND: We measured 34 metabolites of current-use pesticides and other
      precursor compounds in urine samples collected twice during pregnancy from 538
      women living in the Salinas Valley of California, a highly agricultural area
      (1999-2001). Precursors of these metabolites included fungicides, carbamate,
      organochlorine, organophosphorus (OP), and pyrethroid insecticides, and triazine
      and chloroacetanilide herbicides. We also measured ethylenethiourea, a metabolite
      of the ethylene-bisdithiocarbamate fungicides. Repeat measurements of the
      compounds presented here have not been reported in pregnant women previously. To
      understand the impact of the women's regional environment on these findings, we
      compared metabolite concentrations from the CHAMACOS (Center for the Health
      Assessment of Mothers and Children of Salinas) cohort with U.S. national
      reference data for 342 pregnant women sampled by the National Health and
      Nutrition Examination Survey (1999-2002). RESULTS: The eight metabolites detected
      in > 50% of samples [2,4-dichlorophenol (2,4-DCP); 2,5-dichlorophenol (2,5-DCP);
      1- and 2-naphthol; ortho-phenylphenol (ORTH); para-nitrophenol (PNP); 2,4,6
      trichlorophenol (2,4,6-TCP); and 3,4,6-trichloro-2-pyridinol (TCPy)] may be
      related to home or agricultural pesticide use in the Salinas Valley, household
      products, and other sources of chlorinated phenols. More than 78% of women in
      this study had detectable levels of at least one of the OP pesticide-specific
      metabolites that we measured, and > 30% had two or more. The 95th percentile
      values of six of the most commonly detected (> 50%) compounds were significantly
      higher among the CHAMACOS women after controlling for age, race, socioeconomic
      status, and smoking [(2,4-DCP; 2,5-DCP; ORTH; PNP; 2,4,6-TCP; and TCPy); quantile
      regression p < 0.05]. CONCLUSIONS: Findings suggest that the CHAMACOS cohort has
      an additional burden of precursor pesticide exposure compared with the national
      sample, possibly from living and/or working in an agricultural area.

PMID- 20129874
TI  - Urinary concentrations of metabolites of pyrethroid insecticides in the general
      U.S. population: National Health and Nutrition Examination Survey 1999-2002.
AB  - BACKGROUND: Pyrethroid insecticides are the most commonly used residential
      insecticides in the United States. OBJECTIVES: Our objective was to assess human
      exposure via biomonitoring to pyrethroid insecticides in a representative sample
      of the general U.S. population >or= 6 years of age. METHODS: By using isotope
      dilution high-performance liquid chromatography/electrospray chemical
      ionization/tandem mass spectrometry, we measured five urinary metabolites of
      pyrethroid insecticides in 5,046 samples collected as a part of the 1999-2002
      National Health and Nutrition Examination Survey (NHANES). Univariate,
      multivariate, and Pearson correlation analyses were performed using SUDAAN and
      SAS software, incorporating the appropriate sample weights into the analyses.
      Multivariate analyses included age, sex, race/ethnicity, creatinine, fasting
      status, and urine collection time as covariates. RESULTS: We detected 3
      phenoxybenzoic acid (3PBA), a metabolite common to many pyrethroid insecticides,
      in more than 70% of the samples. The least-squares geometric mean (LSGM)
      concentration (corrected for covariates) of 3PBA and the frequency of detection
      increased from 1999-2000 (0.292 ng/mL) to 2001-2002 (0.318 ng/mL) but not
      significantly. Non-Hispanic blacks had significantly higher LSGM 3PBA
      concentrations than did non-Hispanic whites and Mexican Americans in the 2001
      2002 survey period and in the combined 4-year survey periods but not in the 1999
      2000 survey period. Children had significantly higher LSGM concentrations of 3PBA
      than did adolescents in both NHANES periods and than adults in NHANES 1999-2000.
      Cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid
      were highly correlated with each other and with 3PBA, suggesting that urinary
      3PBA was derived primarily from exposure to permethrin, cypermethrin, or their
      degradates. CONCLUSIONS: Pyrethroid insecticide exposure in the U.S. population
      is widespread, and the presence of its metabolites in the urine of U.S. residents
      indicates that children may have higher exposures than adolescents and adults.

PMID- 20129875
TI  - The estimated incidence of gastrointestinal stromal tumors in France. Results of
      PROGIST study conducted among pathologists.
AB  - The aim of this study was to investigate the incidence of gastrointestinal
      stromal tumors (GISTs) in France. METHOD: This prospective epidemiological study
      was performed among pathologists who were asked to report exhaustively the cases
      of GIST over a one-year period. RESULTS: Five hundred ninety-one cases of GISTs
      were reported, 535 new cases and 56 cases of relapse. So, the estimated incidence
      of GIST in France was 8.5-10 cases per million inhabitants in 2005. The main
      characteristics of the new GIST cases were as follows: mean age 65 (+/- 13.2)
      years; 48.6% men; circumstances of discovery: fortuitous 30.5%, symptomatic
      46.5%, and unknown 23%. The primary tumor locations were stomach 63.7%, small
      intestine 21.5%, mesentery 6.5%, colon and rectum 3.2%, esophagus 0.7%, and 4.3%
      locations were listed as unknown. Globally, 95.3% of GISTs were cKIT (CD117)
      positive. Based on tumor size and mitotic rate, among the 490 localized GISTs,
      14.7% were considered to have a very low prognostic risk, 25.5% low risk, 23.1%
      intermediate risk, and 23.1% high risk. CONCLUSIONS: This study provides for the
      first time an estimation of the incidence of GISTs in France, and the results are
      comparable to what has been reported in studies in other European countries.

PMID- 20129876
TI  - Incidence and time course of dentinal hypersensitivity after periodontal surgery.
AB  - This study sought to characterize the incidence and clinical progression of
      dentinal hypersensitivity after periodontal surgery. Fourteen patients scheduled
      for open-flap periodontal debridement participated in the study. Ten subjects
      completed the study and were evaluated for six consecutive weeks after
      periodontal surgery. Tactile hypersensitivity was assessed using the Yeaple
      probe; thermal hypersensitivity measurements were obtained using a blast of air
      from the air/water syringe; and subjective hypersensitivity measurements were
      obtained using a visual analog scale (VAS). Measurements were taken
      preoperatively, one week postoperatively, and once a week for the next five
      consecutive weeks, for a total of six measurements after periodontal surgery.
      Depending on the stimuli used, dentinal hypersensitivity at one week after
      periodontal surgery ranged from 67 to 76%. Preoperative tactile and thermal
      hypersensitivity incidence combined was 30% at baseline. One week after
      periodontal surgery, the combined incidence had increased to 79%; at six weeks
      postsurgery, it had decreased to 45%. This study shows that postoperative
      dentinal hypersensitivity increases at one and three weeks after open-flap
      periodontal debridement before spontaneously and gradually decreasing to levels
      similar to those presurgery, even in the absence of desensitizing therapy.

PMID- 20129877
TI  - Toothache referred from heart disease and lung cancer via the vagus nerve.
AB  - New epidemiologic evidence suggests that referred craniofacial pain in coronary
      heart disease is more common than previously believed. Current medical reports
      suggest that in addition to coronary disease, thoracic disorders such as aortic
      dissection, pericarditis, and lung cancer can cause referred craniofacial pain.
      Recent physiologic evidence from animals and humans suggests that the vagus nerve
      mediates this referral of cardiac pain to the maxillofacial region. This article
      discusses the critical role of the dentist in patient education and recognition
      of referred head and neck pain in thoracic disease, in relation to the need for
      prompt medical treatment for these life-threatening conditions.

PMID- 20129878
TI  - Complications associated with anesthesia administered for dental treatment.
AB  - This assessment sought to identify and quantify complications that occur with
      anesthesia administration during dental treatment of consecutive patients who
      received care through the University of Pittsburgh School of Dental Medicine's
      (UPSDM) Department of Anesthesiology. This prospective study was completed by
      participating anesthesia caregivers at the UPSDM as a case-by-case evaluation. A
      standardized form delineating possible complications was used to collect data
      following 286 consecutive outpatient anesthetic cases administered within the
      UPSDM. After statistical analysis of five types of administered anesthesia, the
      overall complication rate was 22.4% in 286 cases. All of the complications were
      considered to be mild (90.6%) or moderate (9.4%); there were no reports of severe
      complications. The complications encountered most frequently were airway
      obstruction (18 reports) and occurrence of nausea/vomiting (12 reports). ASA
      classification, anesthetic technique, pre-existing medical findings, and the type
      of dental procedure performed all were variables that were found to affect the
      incidence of anesthesia-related complications. The overall complication rate from
      anesthesia administered during dental care is similar to or less than that
      reported within the hospital operating system environment.

PMID- 20129879
TI  - A provisional fixed partial denture for an implant prosthesis.
AB  - This article presents a technique for fabricating an esthetic provisional
      restoration on multiple implants. Fabricating a provisional restoration allows
      the dentist to make a replica of the desired restoration. The incisal edge can be
      placed for esthetics and function in the new provisional restoration, allowing
      patients to evaluate comfort and test their ability to speak with the contour of
      the provisional restoration. Patients can evaluate both the ease of cleaning the
      restoration and how tissue esthetics can be duplicated to their satisfaction. By
      adding acrylic resin to or removing it from the provisional, the dentist can
      easily change the restoration until the patient is satisfied with the esthetic
      and functional result. This technique will allow the dentist to fabricate the
      provisional prosthesis quickly, while the patient is in the chair.

PMID- 20129880
TI  - Conservative approach to dental extractions in patients on anticoagulant therapy:
      A clinical study.
AB  - This clinical study reviewed dental surgical extractions that were performed on
      532 patients diagnosed at risk of thromboembolism without interrupting their
      anticoagulant therapy. The results confirmed that anticoagulant therapy can be
      modified successfully and does not need to be interrupted, which can carry
      significant risks.

PMID- 20129881
TI  - Influence of the coloring agent concentration on bleaching gel and pulp chamber
      temperatures during dental bleaching.
AB  - This study evaluated the influence of the coloring agent concentration on the
      temperature of the gel layer and pulp chamber during dental bleaching with an
      LED/laser light source. Ten human incisors and a digital thermometer with K-type
      thermocouples were used. Using a high-speed spherical diamond bur, endodontic
      access was gained through openings on the lingual faces until pulp chamber was
      exposed. One end of the thermocouple was placed on the labial surface (immersed
      in bleaching gel) and the other end in the pulp chamber. The same 10 specimens
      were used in the 12 groups, according to the type and concentration of bleaching
      gel. Each bleaching gel was used in four different concentrations: manipulated
      without coloring, with normal quantity recommended by the manufacturer, with
      double the recommended amount of coloring, and with triple the recommended amount
      of coloring. The temperature rise was measured every 30 seconds for three minutes
      with a K-type thermocouple. The data were analyzed by ANOVA to examine the
      concentration and type of bleaching gel. This test was followed by Tukey's test,
      which was performed independently for the gel at the labial surface and the pulp
      chamber (a = 5%). For both surfaces, values of p = 0.00 were obtained for all
      factors and for the interaction between them. The varying concentrations of
      coloring agent produced statistically significant differences in terms of
      temperature increase for both the gel layer and the pulp chamber during
      activation.

PMID- 20129882
TI  - Compliance with periodontal maintenance at the University of Pittsburgh:
      Retrospective analysis of 315 cases.
AB  - Maintenance care is the most important part of periodontal treatment because
      maintenance - adherence to the schedule of recall dental appointments after
      treatment - is believed to be the key in preventing the recurrence of periodontal
      disease. This article is a retrospective analysis of 315 cases from the
      Department of Periodontics and Preventive Dentistry at the University of
      Pittsburgh to determine compliance with periodontal maintenance schedules over a
      two-year period. Following the completion of periodontal surgical treatment,
      patients were placed on a regimen of maintenance care that included recalls every
      three months, professional prophylaxis by the hygiene faculty, and repeated
      instructions in home self-care. Medical records and patient charts of 315
      subjects were selected randomly and reviewed in terms of the patient's attending
      the scheduled recall visit. It was hypothesized that female subjects would show
      better compliance with the maintenance care regimen than male subjects, as
      suggested in the literature. Among the 315 subjects, 112 (54 women and 58 men)
      followed the recommended recall schedule; 30% ultimately returned for the three
      month prophylaxis recall visit after the initial periodontal surgical
      appointment, and thus were considered to have complied with the suggested
      maintenance program. The investigators failed to reject the stated hypothesis
      that women would display better compliance than men (p = 0.3).

PMID- 20129883
TI  - Comparison of the amount of transportation when using a precurved instrument in a
      sonic handpiece vs. nickel-titanium rotary files.
AB  - Three-dimensional cleaning of the root canal system along its basic shape is one
      of the main goals in endodontics. A sonic handpiece is a helpful adjunct that can
      aid in accomplishing this goal; however, its use has been limited due to the risk
      of transporting the apices' original position. Precurving sonic files may reduce
      transportation. For this study, 35 plastic blocks were randomly assigned to two
      groups, one of which (n = 16) was instrumented by nickel-titanium rotary files
      (to a size 40), while the second group (n = 18) was instrumented by a sonic
      handpiece with precurved files. Similar blocks were instrumented with noncurved
      sonic files and used as controls. Radiographs taken before and after
      instrumentation were compared. Of the 18 apices instrumented by the sonic
      handpiece with precurved files, seven were not transported. By comparison, 8 of
      the 16 apices instrumented by nickel-titanium files did not transport. When
      transportation did occur, it was less than 0.5 mm for either technique. The
      control blocks instrumented by the sonic handpiece with straight files were
      transported significantly. An ANOVA with a post hoc Tukey's test showed no
      statistically significant difference between the file systems. Based on the
      results, precurving sonic files to match the canal contour may allow for
      efficient cleaning without undue transportation.

PMID- 20129885
TI  - Great news.

PMID- 20129884
TI  - Sugar consumption and dental health: Is there a correlation?
AB  - This study investigated the correlation between sugar consumption and dental
      caries in a random sample of 184 schoolchildren (all 12 years of age) from public
      and private schools in Piracicaba, Brazil. A seven-day diet record was
      administered in a cross-sectional survey. Diet records were used to determine the
      frequency of sugar consumption both during and between meals. Socioeconomic and
      behavioral variables were collected in a semi-structured questionnaire. Using
      Community Periodontal Index (CPI) probes and mirrors and following WHO
      recommendations, a calibrated dentist assessed the number of decayed, missing,
      and filled surfaces (DMFS) on permanent teeth, the CPI, and the number of
      noncavitated (NC) carious lesions. Data analysis demonstrated significant
      correlations between NC carious lesions and sugar consumption during morning
      snack (p = 0.0282; r = 0.1618), NC carious lesions and sugar consumption during
      lunch (p = 0.0539; r = 0.1425), monthly family income and sugar consumption
      during dinner (p < 0.001; r = 0.2970), father's education and sugar consumption
      during dinner (p = 0.0027; r = 0.2430), and onset of toothbrushing and sugar
      consumption during dinner (p = 0.0159; r = 0.1786). A high consumption of sweet
      foods/beverages occurred between meals (mean = 17.48; standard deviation =
      14.68). Although there was no correlation between DMFS and sugar consumption,
      there was a correlation between NC carious lesions and sugar consumption,
      indicating that the rational use of sugar is an important factor in caries
      prevention.

PMID- 20129886
TI  - Platelet inhibitors: update on clopidogrel (Plavix) and the recently approved
      prasugrel (Effient).

PMID- 20129887
TI  - Decision-making in full-arch restorative dentistry: part 2.
AB  - A multitude of decisions must be made when performing restorative dentistry,
      particularly full-arch restorative dentistry. The likelihood of making the
      correct decision can be improved if the dentist attends appropriate high-quality
      continuing education, reads refereed literature, works with an experienced
      mentor, and has some personal experience with this type of dentistry. Consulting
      with a laboratory technician and a periodontist (or other specialist) before
      beginning a full-arch case may help as well. Finding one's "comfort zone" and
      staying within that zone will benefit both the patient and the dentist; a dentist
      who feels uncomfortable attempting a procedure (particularly one beyond his or
      her capability) should refer the patient to a specialist. Full-arch dentistry can
      be very rewarding in many ways (Fig. 10-12), but it also can be quite the
      opposite if the wrong decisions are made at any stage of the process.

PMID- 20129888
TI  - Robinow syndrome, Cockayne syndrome, and Pfeiffer syndrome: an overview of
      physical, neurological, and oral characteristics.
AB  - The general population expects dentists to be well-versed in the typical and
      atypical orofacial characteristics of all potential patients. As a result,
      dentists must possess a reasonable amount of knowledge concerning the physical
      and intraoral traits associated with developmental disorders such as those
      associated with Robinow syndrome, Cockayne syndrome, and Pfeiffer syndrome. None
      of the physical, neurological, or oral anomalies discussed in this column present
      insurmountable barriers to providing dental care. Dental techniques and
      procedures performed on patients with any of these syndromes will be identical or
      very similar to those done on any other patient.

PMID- 20129889
TI  - Mouth breathing: adverse effects on facial growth, health, academics, and
      behavior.
AB  - The vast majority of health care professionals are unaware of the negative impact
      of upper airway obstruction (mouth breathing) on normal facial growth and
      physiologic health. Children whose mouth breathing is untreated may develop long,
      narrow faces, narrow mouths, high palatal vaults, dental malocclusion, gummy
      smiles, and many other unattractive facial features, such as skeletal Class II or
      Class III facial profiles. These children do not sleep well at night due to
      obstructed airways; this lack of sleep can adversely affect their growth and
      academic performance. Many of these children are misdiagnosed with attention
      deficit disorder (ADD) and hyperactivity. It is important for the entire health
      care community (including general and pediatric dentists) to screen and diagnose
      for mouth breathing in adults and in children as young as 5 years of age. If
      mouth breathing is treated early, its negative effect on facial and dental
      development and the medical and social problems associated with it can be reduced
      or averted.

PMID- 20129890
TI  - Outcomes of root canal treatment in Dental Practice-Based Research Network
      practices.
AB  - This study sought to quantify the incidence of root canal treatment (RCT) failure
      and identify its predictors in root canals that were performed or referred by
      general dentistry practices in a practice-based research network (PBRN). This
      retrospective cohort study involved 174 endodontically treated teeth. Mean
      duration from initial therapy to follow-up was 8.6 years. Permanent restorations
      were ultimately placed in 89% of teeth, although 18% of teeth were ultimately
      extracted anyway. Receiving a permanent restoration was a significant predictor
      of treatment failure (in other words, patients who did not receive a permanent
      restoration were more likely to experience RCT failure), whether failure was
      determined clinically or radiographically. This study of PBRN practices suggests
      a higher failure rate compared with studies that utilized highly controlled
      environments or populations with high levels of dental insurance.

PMID- 20129891
TI  - Use of fluorides in dental caries management.
AB  - Fluoride is commonly and widely used to prevent and even arrest caries. The
      clinical effects of fluorides depend on the chemical compounds utilized and the
      methods used to apply the fluoride ion to the surface of the tooth. Fluorosis has
      been reported in conjunction with increased doses of fluoride. A coordinated
      approach to fluoride delivery is essential to avoid the risk of fluorosis.

PMID- 20129892
TI  - Panoramic radiography and its role in the diagnosis of systemic disorders.
AB  - This article presents a case report in which a systemic disease was first
      suspected by viewing a panoramic radiograph. A 49-year-old man sought prosthetic
      rehabilitation with implants. Panoramic radiography revealed an osteolysis of
      poorly defined limits in the apical region of teeth No. 26 to 28. The patient's
      medical history included the recent removal of a giant cell lesion from the left
      tibia. During palpation of the neck, a fixed nodule was detected on the superior
      portion of the left thyroid gland. Biochemical tests showed elevated levels of
      serum alkaline osphatase, serum calcium, and parathyroid hormone. As the serum
      phosphate was low, the final diagnosis was primary hyperparathyroidism. A CT scan
      showed a hypodense lesion involving teeth No. 26 to 28, with preserved cortical
      bone. A whole-body bone scintigraphy showed lesions in the mandible and other
      long bones. A high radiopharmaceutical capitation was present in the left
      parathyroid gland. The patient was referred to a head and neck surgeon, who
      removed the left thyroid lobule and the parathyroid gland. The microscopic
      diagnosis was parathyroid carcinoma. After eight months of follow-up, the
      mandibular lesion disappeared.

PMID- 20129893
TI  - The antimicrobial efficacy of commercial dentifrices.
AB  - This investigation compared the effects of a fluoride dentifrice and toothpastes
      formulated with antimicrobial ingredients (stannous fluoride and
      triclosan/copolymer) on oral micro-organisms, including those found in samples
      taken from the human oral cavity. Microbiological techniques determined the
      minimum inhibitory concentrations (MICs) of each dentifrice necessary to inhibit
      the growth of bacterial strains from the healthy oral cavity, as well as those
      found in dental caries, periodontal disease, and halitosis. Ex vivo studies
      utilized oral rinse samples and supragingival plaque from adults to determine
      antimicrobial effects on the entire microbial diversity of these samples,
      including biofilm-derived micro-organisms. The triclosan/copolymer dentifrice
      demonstrated the lowest MICs and significantly inhibited Gram-positive and Gram
      negative bacteria (including the periodontal pathogens Aggregatibacter
      actinomycetemcomitans, Eikenella corrodens, and Fusobacterium nucleatum). In the
      ex vivo tests, the triclosan/copolymer dentifrice demonstrated substantial
      inhibition in the oral rinse samples over each treatment period (p > 0.0005) as
      compared to either the fluoride or stannous fluoride dentifrices. Similarly, the
      triclosan/copolymer dentifrice demonstrated the highest inhibition of micro
      organisms in the supragingival plaque biofilm (p < 0.0005). No significant
      differences were observed between the fluoride and stannous fluoride dentifrices
      (p > 0.5).

PMID- 20129894
TI  - Allergy to nickel in orthodontic patients: clinical and histopathologic
      evaluation.
AB  - Adverse reactions stemming from the use of fixed and removable orthodontic
      appliances have been a cause for concern for both orthodontists and researchers
      in the health care field. Nickel often has been indicated as a biological
      sensitizer capable of causing short- and long-term reactions (Type IV immune
      response). This article addresses the clinical and diagnostic aspects of nickel
      related reactions in orthodontic patients, based on the literature. A case report
      highlighting the periodontal, clinical, and histopathologic aspects of an
      allergic patient in orthodontic treatment is presented.

PMID- 20129895
TI  - Developmental oronasal fistula of the incisive papilla.
AB  - Various terms (including patent nasopalatine fistula and patent nasopalatine
      duct) have been used to describe the presence of a developmental fistulous tract
      that connects the oral and nasal cavities through an oral opening located at the
      incisive papilla. Reportedly, this condition is a rare developmental variant;
      approximately 40 cases have been reported in the literature. Because awareness of
      this entity is important to avoid misdiagnosis, this article presents the
      clinical and conebeam computed tomography findings of two cases. Based on a
      review of the development of the nasopalatine structures in man, the authors
      propose that this entity be classified as a developmental oronasal fistula of the
      incisive papilla.

PMID- 20129896
TI  - Interdisciplinary approach to traumatized permanent anterior teeth: case report
      and 10-year follow-up.
AB  - This article presents a case report (including the 10-year follow-up) of a 10
      year-old patient who suffered displacement of the maxillary right central
      incisor, intrusion of the maxillary left central incisor, and crown fractures to
      the mesial angles of these teeth as a result of dental trauma. Treatment involved
      an interdisciplinary approach that utilized a pediatric dentist, an endodontist,
      and an orthodontist.

PMID- 20129897
TI  - Pebbly gingival mass in a 7-year-old boy. Squamous papilloma.

PMID- 20129898
TI  - Oral mucosal and glossal lesions in a 14-year-old boy. Juvenile lichen planus.

PMID- 20129900
TI  - Popular Arts and Education in Community-Based Participatory Research (CBPR): on
      the subtle craft of developing and enhancing channels for clear conversations
      among CBPR partners.
AB  - Community-Based Participatory Research (CBPR) is a methodology hinged on flexible
      power relationships and unobstructed flow of expert and local knowledge among
      project partners. Success in CBPR depends on authentic dialogue, free flow of
      information, and trust. But accurate, unmediated, and timely channels of
      communication, while key to successful CBPR, are difficult to create and
      maintain. As participatory methodologies evolve, popular arts and education
      techniques have increasingly taken center stage as culturally fluent,
      bidirectional modalities for conveying information, building responsive channels
      for communication, promoting policy, and enhancing the effectiveness of
      grassroots organizing.

PMID- 20129901
TI  - Project REECH: using theatre arts to authenticate local knowledge.
AB  - Marginalized communities need to be heard and validated within their local
      context, so that individual and community support can be garnered and ownership
      of the concerns can be embraced. This article reports on three modalities that
      were used in the community outreach activities of Project REECH. The goal of
      Project REECH is to engage residents in low-income neighborhoods in a dialogue
      with researchers to identify the major health concerns in their community. With
      the aid of these community conversations, the goal is to identify and train
      community residents to conduct such community-identified research in their
      neighborhoods. This article primarily explores and evaluates the use and
      effectiveness of an arts modality called Playback Theatre. Also, it briefly
      reports on the use of Readers' Theatre and graphic facilitation to aid in the
      dissemination of the data collected from these community conversations.

PMID- 20129902
TI  - Homelessness among older african-american women: interpreting a serious social
      issue through the arts in community-based participatory action research.
AB  - This article describes the incorporation of the arts into a community-based
      participatory action research (CBPAR) project formulated to develop and test
      practices for helping homeless older African-American women. Studying how older
      African-American women become homeless has evolved into developing and testing
      promising interventions by the Leaving Homelessness Intervention Research Project
      (LHIRP). The women's participation in creative group activities helped them to
      communicate their experience with homelessness, express their concerns, develop
      personal strengths, and obtained mutual understanding. The use of multiple art
      forms has revealed a number of creative strengths among the participants, which
      have in turn inspired innovative artistic strategies and methodologies as part of
      the multiple methods that LHIRP incorporates. These interventions have been
      useful in helping participants resolve their homelessness. The role and benefit
      of the arts in CBPAR is described to show how creative activities help
      researchers and the public to better understand the complexities of homelessness.

PMID- 20129903
TI  - Using lay health promoters in occupational health: outcome evaluation in a sample
      of Latino poultry-processing workers.
AB  - Lay Health Promoters (LHPs) are widely used in community health education, but
      their use and evaluation in occupational health has been limited to farm workers.
      Evaluation data were collected from 30 randomly selected Latino poultry
      processing workers who had an encounter with an LHP who delivered Maria's Story,
      an occupational health lesson about cumulative trauma disorders (CTDs).
      Participants had good recall of Maria's Story. Most participants (n = 18, 60%)
      could identify the primary occupational health exposure linked to CTDs, more than
      50% of participants (n = 16) could recall one or more ways of preventing CTDs,
      and 43.3% (n = 13) described in detail recommended treatments. Nearly one-half (n
      = 12) reported an occupational health behavior change after hearing Maria's
      Story. The results of this study suggest that LHPs may be effective in promoting
      occupational health and reducing occupational health disparities among ethnic
      minorities in high-risk occupations.

PMID- 20129904
TI  - Behind the fence forum theater: an arts performance partnership to address lupus
      and environmental justice.
AB  - Community-based participatory research (CBPR) is a method to improve
      environmental quality in communities primarily inhabited by minorities or low
      income families. The Buffalo Lupus Project was a CBPR partnership formed to
      explore the relationship between a local waste site and high rates of lupus. The
      "Behind the Fence" Community Environmental Forum Theater project was able to
      successfully funnel the results of scientific research and ongoing activities to
      the community by utilizing a Forum Theater approach, image-making techniques, an
      interactive workshop, and energetic public performance. Filming of project
      activities will expand the reach of that original performance and provide other
      communities with a potential model for similar efforts.

PMID- 20129905
TI  - Investigation: revelations about Three Mile Island disaster raise doubts over
      nuclear plant safety: a special facing south investigation by Sue Sturgis.
AB  - A series of mishaps in a reactor at the Three Mile Island (TMI) nuclear plant led
      to the 1979 meltdown of almost half the uranium fuel and uncontrolled releases of
      radiation into the air and surrounding Susquehanna River. It was the single worst
      disaster ever to befall the U.S. nuclear power industry. Health physics
      technician Randall Thompson's story about what he witnessed while monitoring
      radiation there after the incident is being publicly disclosed for the first
      time. It is supported by a growing body of evidence and it contradicts the U.S.
      government's contention that the TMI accident posed no threat to the public.
      Thompson and his wife, a nuclear health physicist who also worked at TMI in the
      disaster's wake, warn that the government's failure to acknowledge the full scope
      of the disaster is leading officials to underestimate the risks posed by a new
      generation of nuclear power plants.

PMID- 20129906
TI  - Views of a Cal/OSHA Inspector.
AB  - Retiring CAL/OSHA Industrial Hygienist and Senior Safety Engineer Jack Oudiz
      offers his thoughts in the nature of a voluntary "exit interview" on his years
      working for the agency and its performance in its mission.

PMID- 20129907
TI  - The Goodyear explosion: ensuring our nation is secure by developing a risk
      management framework for Homeland Security.

PMID- 20129908
TI  - Autoworkers write to the President.

PMID- 20129913
TI  - Preliminary construction of a service provider--informed domestic violence
      research agenda.
AB  - This article presents the results of a statewide survey of domestic violence (DV)
      service providers that focused on the needs, background characteristics, and
      opinions of service providers related to research. The survey included an
      examination of service providers' motivation for working in the field, research
      background and training, and perceptions of research as well as the topics they
      believe are important for researchers to study, the resources they consult to
      learn about DV, and their suggestions to help researchers learn more about the
      nature of their work. The results are integrated into a preliminary agenda for
      future DV research that accounts for the needs and insight of service providers.

PMID- 20129912
TI  - Chronic social defeat stress disrupts regulation of lipid synthesis.
AB  - Several psychiatric disorders increase the risk of cardiovascular disease,
      including posttraumatic stress disorder and major depression. While the precise
      mechanism for this association has not yet been established, it has been shown
      that certain disorders promote an unfavorable lipid profile. To study the
      interaction of stress and lipid dysregulation, we utilized chronic social defeat
      stress (CSDS), a mouse model of chronic stress with features of posttraumatic
      stress disorder and major depression. Following exposure to CSDS, mice were given
      access to either regular chow or a Western-style diet high in fat and cholesterol
      (HFD). The combination of social stress and HFD resulted in significant
      perturbations in lipid regulation, including two key features of the metabolic
      syndrome: increased plasma levels of non-HDL cholesterol and intrahepatic
      accumulation of triglycerides. These effects were accompanied by a number of
      changes in the expression of hepatic genes involved in lipid regulation.
      Transcriptional activity of LXR, SREBP1c, and ChREBP were significantly affected
      by exposure to HFD and CSDS. We present CSDS as a model of social stress induced
      lipid dysregulation and propose that social stress alters lipid metabolism by
      increasing transcriptional activity of genes involved in lipid synthesis.

PMID- 20129914
TI  - Comparing revictimization in two groups of marginalized women.
AB  - This study examines physical and sexual revictimization in a random sample of
      incarcerated and poor, urban, nonincarcerated women using multiple measures of
      physical and sexual child abuse. Researchers used hierarchical logistic
      regression to compare rates of revictimization and the strength of the
      association between child abuse and adult victimization using two measures of
      child physical abuse and four measures of child sexual abuse. Incarcerated women
      had higher rates of revictimization than did nonincarcerated women. Child abuse
      and adult incarceration were directly associated with adult victimization;
      interactions between child abuse and incarceration were associated with adult
      victimization for only a few definitions of child abuse. Findings suggest that
      the relationship between child abuse and adult victimization is robust and that
      factors in incarcerated women's lives further increase the probability of adult
      victimization.

PMID- 20129915
TI  - Differences in depression, posttraumatic stress disorder, and lifetime trauma
      exposure in formerly abused women with mild versus moderate to severe chronic
      pain.
AB  - Although associations between intimate partner violence, chronic pain,
      depression, posttraumatic stress disorder (PTSD), and lifetime trauma exposure
      are well known, previous studies are limited by their recruitment of women from
      shelters. These relationships were explored with a community-based sample of
      formerly abused women ( N = 84). Seventy-seven percent of women reported pain of
      >3 months duration, and 75% had moderate to severe pain. Based on logistic
      regression analysis, women with moderate to severe chronic pain were
      significantly less likely to be employed, had more depressive symptoms, and were
      in the abusive relationship longer than women in mild chronic pain. Both pain
      severity groups had equally high levels of depressive and PTSD symptoms and
      multiple trauma exposures. Findings document the persistence of significant
      symptomatology in formerly abused women.

PMID- 20129916
TI  - Angiogenin-induced tRNA-derived stress-induced RNAs promote stress-induced stress
      granule assembly.
AB  - Angiogenin (ANG) is a secreted ribonuclease that cleaves tRNA to initiate a
      stress-response program in mammalian cells. Here we show that ANG inhibits
      protein synthesis and promotes arsenite- and pateamine A-induced assembly of
      stress granules (SGs). These effects are abrogated in cells transfected with the
      ANG inhibitor RNH1. Transfection of natural or synthetic 5'- but not 3'-tRNA
      fragments (tRNA-derived stress-induced RNAs; tiRNAs) induces the phospho
      eukaryotic translation initiation factor 2alpha-independent assembly of SGs.
      Natural 5'-tiRNAs but not 3'-tiRNAs are capped with a 5'-monophosphate that is
      required for optimal SG assembly. These findings reveal that SG assembly is a
      component of the ANG- and tiRNA-induced stress response program.

PMID- 20129917
TI  - Pitx2-dependent occupancy by histone deacetylases is associated with T-box gene
      regulation in mammalian abdominal tissue.
AB  - The homeodomain transcription factor Pitx2 and the T-box transcription factors
      are essential for organogenesis. Pitx2 and T-box genes are induced by growth
      factors and function as transcriptional activators or repressors. Gene expression
      analyses on abdominal tissue were used to identify seven of the T-box genes of
      the genome as Pitx2 target genes in the abdomen at embryonic day.10.5. Pitx2
      activated Tbx4, Tbx15, and Mga and repressed Tbx1, Tbx2, Tbx5, and Tbx6
      expression. As expected, activated genes showed reduced expression patterns, and
      repressed T-box genes showed increased expression patterns in the abdomen of
      Pitx2 mutants. Pitx2 occupied chromatin sites near all of these T-box genes. Co
      occupancy by coactivators, corepressors, and histone acetylation at these sites
      was frequently Pitx2-dependent. Genes repressed by Pitx2 generally showed
      increased histone acetylation and decreased histone deacetylase
      (HDAC)/corepressor occupancy in Pitx2 mutants. The lower N-CoR, HDAC1, and HDAC3
      occupancy observed at multiple sites along Tbx1 chromatin in mutants is
      consistent with the model that increased histone acetylation and gene expression
      of Tbx1 may result from a loss of recruitment of corepressors by Pitx2. Genes
      activated by Pitx2 showed less consistent patterns in chromatin analyses. Reduced
      H4 acetylation and increased HDAC1/nuclear receptor corepressor (N-CoR) occupancy
      at some Tbx4 sites were accompanied by increased H3 acetylation and reduced HDAC3
      occupancy at the same or other more distal chromatin sites in mutants. Pitx2
      dependent occupancy by corepressors resulted in alteration of the acetylation
      levels of several T-box genes, whereas Pitx2-dependent occupancy by coactivators
      was more site-localized. These studies will provide the basic scientific
      underpinning to understand abdominal wall syndromes.

PMID- 20129918
TI  - Discovery and characterization of an amidinotransferase involved in the
      modification of archaeal tRNA.
AB  - The presence of the 7-deazaguanosine derivative archaeosine (G(+)) at position 15
      in tRNA is one of the diagnostic molecular characteristics of the Archaea. The
      biosynthesis of this modified nucleoside is especially complex, involving the
      initial production of 7-cyano-7-deazaguanine (preQ(0)), an advanced precursor
      that is produced in a tRNA-independent portion of the biosynthesis, followed by
      its insertion into the tRNA by the enzyme tRNA-guanine transglycosylase (arcTGT),
      which replaces the target guanine base yielding preQ(0)-tRNA. The enzymes
      responsible for the biosynthesis of preQ(0) were recently identified, but the
      enzyme(s) catalyzing the conversion of preQ(0)-tRNA to G(+)-tRNA have remained
      elusive. Using a comparative genomics approach, we identified a protein family
      implicated in the late stages of archaeosine biosynthesis. Notably, this family
      is a paralog of arcTGT and is generally annotated as TgtA2. Structure-based
      alignments comparing arcTGT and TgtA2 reveal that TgtA2 lacks key arcTGT
      catalytic residues and contains an additional module. We constructed a Haloferax
      volcanii DeltatgtA2 derivative and demonstrated that tRNA from this strain lacks
      G(+) and instead accumulates preQ(0). We also cloned the corresponding gene from
      Methanocaldococcus jannaschii (mj1022) and characterized the purified recombinant
      enzyme. Recombinant MjTgtA2 was shown to convert preQ(0)-tRNA to G(+)-tRNA using
      several nitrogen sources and to do so in an ATP-independent process. This is the
      only example of the conversion of a nitrile to a formamidine known in biology and
      represents a new class of amidinotransferase chemistry.

PMID- 20129919
TI  - Ligand-induced rearrangements of the GABA(B) receptor revealed by fluorescence
      resonance energy transfer.
AB  - The gamma-aminobutyric acid type B receptor (GABA(B)R), one of the family C G
      protein-coupled receptor members, exists as a heterodimer comprised of subunits
      GB1 and GB2. To clarify the ligand-induced activation mechanism of the GABA(B)R,
      each subunit was fused with either Cerulean or enhanced yellow fluorescent
      protein at its intracellular loop, and fluorescence resonance energy transfer
      (FRET) changes upon agonist application were monitored. As a result, FRET
      decreases were observed between GB1a loop 2 and GB2 loop 2 and between GB1a loop
      2 and GB2 loop 1, suggesting the dissociation of intracellular domains during the
      receptor activation. Both intersubunit FRET pairs were expected to faithfully
      capture the activation of the original receptor as their pharmacological
      properties were highly similar to that of the wild-type receptor. However, the
      intrasubunit data suggest that the receptor activation does not involve major
      structural changes within the transmembrane domain of each subunit. By combining
      the results obtained from two different levels, it was concluded that the
      GABA(B)R activation by agonist is associated with an asymmetrical intersubunit
      rearrangement of GB1a and GB2 on the membrane. This type of activation mode, an
      intersubunit rearrangement without apparent intrahelical structural changes,
      appears commonly shared by the GABA(B)R and the metabotropic glutamate receptor
      1alpha, another family C G-protein-coupled receptor previously studied by our
      group. Nevertheless, the directions of intracellular domain movements and its
      asymmetry observed here highlight the qualitative difference between the two
      receptors.

PMID- 20129920
TI  - Activation of AMP-activated protein kinase by vascular endothelial growth factor
      mediates endothelial angiogenesis independently of nitric-oxide synthase.
AB  - AMP-activated protein kinase (AMPK) is a sensor of cellular energy state and a
      regulator of cellular homeostasis. In endothelial cells, AMPK is stimulated via
      the upstream kinases LKB1 and Ca(2+)/calmodulin-dependent protein kinase kinase
      beta (CaMKKbeta). Previously, AMPK has been reported to activate endothelial
      nitric-oxide synthase (eNOS). Using genetic and pharmacological approaches, we
      show that vascular endothelial growth factor (VEGF) stimulates AMPK in human and
      mice endothelial cells via CaMKKbeta. VEGF-induced AMPK activation is potentiated
      under conditions of energy deprivation induced by 2-deoxyglucose. To investigate
      the role of AMPK in endothelial function, CaMKKbeta, AMPKalpha1, or AMPKalpha2
      was down-regulated by RNA interference, and studies in AMPKalpha1(-/-) mice were
      performed. We demonstrate that AMPK does not mediate eNOS phosphorylation at
      serine residue 1177 or 633, NO- dependent cGMP generation, or Akt phosphorylation
      in response to VEGF. Using inhibitors of eNOS or soluble guanylyl cyclase and
      small interfering RNA against eNOS, we show that NO does not act upstream of
      AMPK. Taken together, these data indicate that VEGF-stimulated AMPK and eNOS
      pathways act independently of each other. However, acetyl-CoA carboxylase, a key
      enzyme in the regulation of fatty acid oxidation, was phosphorylated in response
      to VEGF in an AMPKalpha1- and AMPKalpha2-dependent manner. Our results show that
      AMPKalpha1 plays an essential role in VEGF-induced angiogenesis in vitro (tube
      formation and sprouting from spheroids) and in vivo (Matrigel plug assay). In
      contrast, AMPKalpha2 was not involved in VEGF-triggered sprouting. The data
      suggest that AMPKalpha1 promotes VEGF-induced angiogenesis independently of eNOS,
      possibly by providing energy via inhibition of acetyl-CoA carboxylase.

PMID- 20129921
TI  - Does peroxisome proliferator-activated receptor-gamma (PPAR gamma) protect from
      hypertension directly through effects in the vasculature?
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a ligand
      activated transcription factor of the nuclear hormone receptor superfamily.
      Increasing evidence suggests that PPAR gamma is involved in the regulation of
      vascular function and blood pressure in addition to its well recognized role in
      metabolism. Thiazolidinediones, PPAR gamma agonists, lower blood pressure and
      have protective vascular effects through largely unknown mechanisms. In contrast,
      loss-of-function dominant-negative mutations in human PPAR gamma cause insulin
      resistance and severe early onset hypertension. Recent studies using genetically
      manipulated mouse models have begun to specifically address the importance of
      PPAR gamma in the vasculature. In this minireview, evidence for a protective role
      of PPAR gamma in the endothelium and vascular smooth muscle, derived largely from
      studies of genetically manipulated mice, will be discussed.

PMID- 20129922
TI  - Mechanism of aldolase control of sorting nexin 9 function in endocytosis.
AB  - Sorting nexin 9 (SNX9) functions in a complex with the GTPase dynamin-2 at
      clathrin-coated pits, where it provokes fission of vesicles to complete
      endocytosis. Here the SNX9.dynamin-2 complex binds to clathrin and adapter
      protein complex 2 (AP-2) that line these pits, and this occurs through
      interactions of the low complexity domain (LC4) of SNX9 with AP-2. Intriguingly,
      localization of the SNX9.dynamin-2 complex to clathrin-coated pits is blocked by
      interactions with the abundant glycolytic enzyme aldolase, which also binds to
      the LC4 domain of SNX9. The crystal structure of the LC4 motif of human SNX9 in
      complex with aldolase explains the biochemistry and biology of this interaction,
      where SNX9 binds near the active site of aldolase via residues 165-171 that are
      also required for the interactions of SNX9 with AP-2. Accordingly, SNX9 binding
      to aldolase is structurally precluded by the binding of substrate to the active
      site. Interactions of SNX9 with aldolase are far more extensive and differ from
      those of the actin-nucleating factor WASP with aldolase, indicating considerable
      plasticity in mechanisms that direct the functions of the aldolase as a scaffold
      protein.

PMID- 20129923
TI  - Inhibitory peptides of the sulfotransferase domain of the heparan sulfate enzyme,
      N-deacetylase-N-sulfotransferase-1.
AB  - N-Deacetylase-N-sulfotransferase 1 (Ndst1) catalyzes the initial modification of
      heparan sulfate and heparin during their biosynthesis by removal of acetyl groups
      from subsets of N-acetylglucosamine units and subsequent sulfation of the
      resulting free amino groups. In this study, we used a phage display library to
      select peptides that interact with Ndst1, with the aim of finding inhibitors of
      the enzyme. The phage library consisted of cyclic random 10-mer peptides
      expressed in the phage capsid protein pIII. Selection was based on the ability of
      engineered phage to bind to recombinant murine Ndst1 (mNdst1) and displacement
      with heparin. Peptides that were enriched through multiple cycles of binding and
      disassociation displayed two specific sequences, CRGWRGEKIGNC and CNMQALSMPVTC.
      Both peptides inhibited mNdst1 activity in vitro, however, by distinct
      mechanisms. The peptide CRGWRGEKIGNC presents a chemokine-like repeat motif (BXX,
      where B represents a basic amino acid and X is a noncharged amino acid) and binds
      to heparan sulfate, thus blocking the binding of substrate to the enzyme. The
      peptide NMQALSMPVT inhibits mNdst1 activity by direct interaction with the enzyme
      near the active site. The discovery of inhibitory peptides in this way suggests a
      method for developing peptide inhibitors of heparan sulfate biosynthesis.

PMID- 20129924
TI  - The fibroblast integrin alpha11beta1 is induced in a mechanosensitive manner
      involving activin A and regulates myofibroblast differentiation.
AB  - Fibrotic tissue is characterized by an overabundance of myofibroblasts. Thus,
      understanding the factors that induce myofibroblast differentiation is paramount
      to preventing fibrotic healing. Previous studies have shown that mechanical
      stress derived from the integrin-mediated interaction between extracellular
      matrix and the cytoskeleton promotes myofibroblast differentiation. Integrin
      alpha11beta1 is a collagen receptor on fibroblasts. To determine whether
      alpha11beta1 can act as a mechanosensor to promote the myofibroblast phenotype,
      mouse embryonic fibroblasts and human corneal fibroblasts were utilized. We found
      that alpha11 mRNA and protein levels were up-regulated in mouse embryonic
      fibroblasts grown in attached three-dimensional collagen gels and conversely down
      regulated in cells grown in floating gels. alpha11 up-regulation could be
      prevented by manually detaching the collagen gels or by cytochalasin D treatment.
      Furthermore, SB-431542, an inhibitor of signaling via ALK4, ALK5, and ALK7,
      prevented the up-regulation of alpha11 and the concomitant phosphorylation of
      Smad3 under attached conditions. In attached gels, TGF-beta1 was secreted in its
      inactive form but surprisingly not further activated, thus not influencing
      alpha11 regulation. However, inhibition of activin A attenuated the up-regulation
      of alpha11. To determine the role of alpha11 in myofibroblast differentiation,
      human corneal fibroblasts were transfected with small interfering RNA to alpha11,
      which decreased alpha-smooth muscle actin expression and myofibroblast
      differentiation. Our data suggest that alpha11beta1 is regulated by cell/matrix
      stress involving activin A and Smad3 and that alpha11beta1 regulates
      myofibroblast differentiation.

PMID- 20129925
TI  - Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2
      modulates histone demethylation.
AB  - Distinct lysine methylation marks on histones create dynamic signatures
      deciphered by the "effector" modules, although the underlying mechanisms remain
      unclear. We identified the plant homeodomain- and Jumonji C domain-containing
      protein PHF2 as a novel histone H3K9 demethylase. We show in biochemical and
      crystallographic analyses that PHF2 recognizes histone H3K4 trimethylation
      through its plant homeodomain finger and that this interaction is essential for
      PHF2 occupancy and H3K9 demethylation at rDNA promoters. Our study provides
      molecular insights into the mechanism by which distinct effector domains within a
      protein cooperatively modulate the "cross-talk" of histone modifications.

PMID- 20129926
TI  - A human PMS2 homologue from Aquifex aeolicus stimulates an ATP-dependent DNA
      helicase.
AB  - Mismatch repair in Escherichia coli involves a number of proteins including MutL
      and UvrD. Eukaryotes also possess MutL homologues; however, no UvrD helicase
      homologues have been identified. The hyperthermophilic bacterium Aquifex aeolicus
      has a MutL protein (Aae MutL) that possesses a latent endonuclease activity
      similar to eukaryotic, but different from E. coli, MutL proteins. By sequence
      homology Aq793 is a member of the PcrA/UvrD/Rep helicase subfamily. We expressed
      Aae MutL and the putative A. aeolicus DNA helicase (Aq793) proteins in E. coli.
      Using synthetic oligonucleotide substrates, we observed that lower concentrations
      of Aq793 were required to unwind double-stranded DNA that had a 3'-poly(dT)
      overhang as compared with double-stranded DNA with a 5'-poly(dT) or lacking a
      poly(dT) tail. This unwinding activity was stimulated by adding Aae MutL with
      maximal stimulation observed at an approximately 1.5:1 (MutL:Aq793)
      stoichiometric ratio. The enhancement of Aq793 helicase activity did not require
      the Aae MutL protein to retain endonuclease activity. Furthermore, the C-terminal
      123 amino acid residues of Aae MutL were sufficient to stimulate Aq793 helicase
      activity, albeit at a significantly reduced efficacy. To the best of our
      knowledge this is the first time a human PMS2 homologue has been demonstrated to
      stimulate a PcrA/UvrD/Rep subfamily helicase, and this finding may further our
      understanding of the evolution of the mismatch repair pathway.

PMID- 20129927
TI  - Structure of RecJ exonuclease defines its specificity for single-stranded DNA.
AB  - RecJ is a single-stranded DNA (ssDNA)-specific 5'-3' exonuclease that plays an
      important role in DNA repair and recombination. To elucidate how RecJ achieves
      its high specificity for ssDNA, we determined the entire structures of RecJ both
      in a ligand-free form and in a complex with Mn(2+) or Mg(2+) by x-ray
      crystallography. The entire RecJ consists of four domains that form a molecule
      with an O-like structure. One of two newly identified domains had structural
      similarities to an oligonucleotide/oligosaccharide-binding (OB) fold. The OB fold
      domain alone could bind to DNA, indicating that this domain is a novel member of
      the OB fold superfamily. The truncated RecJ containing only the core domain
      exhibited much lower affinity for the ssDNA substrate compared with intact RecJ.
      These results support the hypothesis that these structural features allow
      specific binding of RecJ to ssDNA. In addition, the structure of the RecJ-Mn(2+)
      complex suggests that the hydrolysis reaction catalyzed by RecJ proceeds through
      a two-metal ion mechanism.

PMID- 20129928
TI  - The Treaty of Lisbon and public health in the EU.

PMID- 20129929
TI  - Self-reported activity limitations among the population aged 20-79 in Estonia: a
      cross-sectional study.
AB  - BACKGROUND: Along with population ageing, limitations in activities of daily
      living constitute a rising health-related burden in demographically advanced
      countries. The present study aims to assess the prevalence of self-reported
      activity limitations derived from chronic conditions and social variation of
      limitations in the subgroups of the population aged 20-79 years in Estonia.
      METHODS: A cross-sectional study employs data from the second round of the
      Estonian Family and Fertility Survey, a national project in the framework of
      Gender and Generation Programme. The target population covers age groups of 20-79
      years. A nationally representative probability sample was drawn from the 2000
      population census. Face-to-face interviews (n = 7855) were conducted in 2004-05.
      RESULTS: The estimated prevalence of activity limitations with chronic conditions
      is 18.5% (95% CI 17.6-19.4) and the prevalence of severe limitations is 10.6%
      (95% CI 9.9-11.3) among the population. The logistic regression model shows
      significant differences in activity limitations associated with age, educational
      attainment and marital status. CONCLUSIONS: Judging from our results and the EU
      structural indicators on health, the prevalence of activity limitations derived
      from chronic conditions is comparatively high in Estonia. The measures to prevent
      activity limitations and disability should receive a higher priority in Estonia.

PMID- 20129930
TI  - Certification of obesity as a cause of death in England 1979-2006.
AB  - BACKGROUND: There is increasing recognition of the importance of obesity as a
      cause of death but it is uncommon for obesity to be certified on death
      certificates. We considered it useful to study what doctors actually do in
      respect of certification of obesity and to study trends, if any, in certification
      practice. METHODS: Analysis of two datasets that include all certified causes of
      death ('mentions'), not just the underlying cause-the Oxford record linkage study
      1979-2006 and English national mortality data 1995-2006. RESULTS: Underlying
      cause mortality identified only a quarter (26% in Oxford, 25% in England) of all
      deaths with obesity as a certified cause. The longstanding Oxford dataset showed
      that there were significant changes over time in the percentage of certificates,
      with mention of obesity, that were coded with obesity as the underlying cause.
      Changes coincided with times of national change in selection and coding rules for
      underlying cause mortality. In the recent English dataset from 1995-2006, mention
      based death rates rose by an average annual rate of 7.5% [95% confidence
      intervals (CI) 6.1-8.8] for men and by 4.0% (2.3-5.7) for women. Analysis of
      mortality based on underlying cause alone would have missed this rise. We report
      on diseases commonly certified alongside obesity on death certificates in
      England. CONCLUSION: There is an emerging trend of increased certification of
      obesity as a cause of death in England. The use of underlying-cause mortality
      statistics alone fails to capture the majority of obesity deaths.

PMID- 20129931
TI  - Expression of a gymnosperm PIN homologous gene correlates with auxin
      immunolocalization pattern at cotyledon formation and in demarcation of the
      procambium during Picea abies somatic embryo development and in seedling tissues.
AB  - In seed plants, the body organization is established during embryogenesis and is
      uniform across gymnosperms and angiosperms, despite differences during early
      embryogeny. Evidence from angiosperms implicates the plant hormone auxin and its
      polar transport, mainly established by the PIN family of auxin efflux
      transporters, in the patterning of embryos. Here, PaPIN1 from Norway spruce
      (Picea abies [L.] Karst.), a gene widely expressed in conifer tissues and organs,
      was characterized and its expression and localization patterns were determined
      with reverse transcription polymerase chain reaction and in situ hybridization
      during somatic embryo development and in seedlings. PaPIN1 shares the predicted
      structure of other PIN proteins, but its central hydrophilic loop is longer than
      most PINs. In phylogenetic analyses, PaPIN1 clusters with Arabidopsis thaliana
      (L.) Heynh. PIN3, PIN4 and PIN7, but its expression pattern also suggests
      similarity to PIN1. The PaPIN1 expression signal was high in the protoderm of pre
      cotyledonary embryos, but not if embryos were pre-treated with the auxin
      transport inhibitor N-1-naphthylphthalamic acid (NPA). This, together with a high
      auxin immunolocalization signal in this cell layer, suggests a role of PaPIN1
      during cotyledon formation. At later stages, high PaPIN1 expression was observed
      in differentiating procambium, running from the tip of incipient cotyledons down
      through the embryo axis and to the root apical meristem (RAM), although the mode
      of RAM specification in conifer embryos differs from that of most angiosperms.
      Also, the PaPIN1 in situ signal was high in seedling root tips including root cap
      columella cells. The results thus suggest that PaPIN1 provides an ancient
      function associated with auxin transport and embryo pattern formation prior to
      the separation of angiosperms and gymnosperms, in spite of some morphological
      differences.

PMID- 20129932
TI  - Perivenous demyelination: association with clinically defined acute disseminated
      encephalomyelitis and comparison with pathologically confirmed multiple
      sclerosis.
AB  - Distinction between acute disseminated encephalomyelitis and acute multiple
      sclerosis is often clinically difficult. Perivenous demyelination is the
      pathological hallmark of acute disseminated encephalomyelitis, whereas confluent
      demyelination is the hallmark of acute multiple sclerosis. We investigated
      whether perivenous demyelination versus confluent demyelination distinguishes
      acute disseminated encephalomyelitis from multiple sclerosis. Patients with
      perivenous demyelination (n = 13; median age 43 years, range 5-67) on brain
      biopsy and/or autopsy, ascertained retrospectively, were compared with a cohort
      with confluent demyelination only (n = 91; 84% multiple sclerosis, 16% isolated
      syndrome at follow-up; median age 39 years, range 10-69). Clinical presentation,
      course and the International Paediatric Multiple Sclerosis Study Group clinical
      criteria for acute disseminated encephalomyelitis were assessed in both cohorts.
      Among the perivenous demyelination cohort, 10 patients had only perivenous
      demyelination and three also had confluent demyelination. All but one patient
      with perivenous demyelination only had a monophasic course, whereas two of three
      with both types had a relapsing course. The perivenous demyelination cohort was
      more likely than the confluent demyelination cohort to present with
      encephalopathy (P < 0.001), depressed level of consciousness (P < 0.001),
      headache (P < 0.001), meningismus (P = 0.04), cerebrospinal fluid pleocytosis (P
      = 0.04) or multifocal enhancing magnetic resonance imaging lesions (P < 0.001). A
      distinct pattern of cortical microglial activation and aggregation without
      associated cortical demyelination was found among six perivenous demyelination
      patients, all of whom had encephalopathy and four of whom had depressed level of
      consciousness. This pattern of cortical pathology was not observed in the
      confluent demyelination cohort, even in one patient with depressed level of
      consciousness. Clinical criteria were 80% sensitive and 91% specific for
      pathologically defined acute disseminated encephalomyelitis (perivenous
      demyelination), but misdiagnosed acute disseminated encephalomyelitis among 9% of
      patients with confluent demyelination and multiple sclerosis diagnosis at last
      follow-up. Perivenous demyelination is associated with meningoencephalopathic
      presentations and a monophasic course. Depressed level of consciousness is a more
      specific clinical criterion for pathologically confirmed acute disseminated
      encephalomyelitis than encephalopathy, which over-diagnosed acute disseminated
      encephalomyelitis among multiple sclerosis patients. A distinct pattern of
      cortical microglial activation without cortical demyelination may be the
      pathological correlate of depressed level of consciousness in acute disseminated
      encephalomyelitis. Although pathological evidence of perivenous demyelination may
      be superior to clinical criteria for diagnosing acute disseminated
      encephalomyelitis, the co-occurrence of perivenous and confluent demyelination in
      some individuals suggests pathogenic overlap between acute disseminated
      encephalomyelitis and multiple sclerosis and misclassification even with biopsy.

PMID- 20129934
TI  - Rapid eye movement sleep behaviour disorder in patients with narcolepsy is
      associated with hypocretin-1 deficiency.
AB  - Rapid eye movement sleep behaviour disorder is characterized by dream-enacting
      behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid
      eye movement sleep behaviour disorder is commonly associated with
      neurodegenerative disorders, but also reported in narcolepsy with cataplexy. Most
      narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement
      sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In
      contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency
      are rare in narcolepsy without cataplexy. We hypothesized that rapid eye movement
      sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin
      deficiency. In our study, rapid eye movement sleep behaviour disorder was
      diagnosed by the International Classification of Sleep Disorders (2nd edition)
      criteria in 63 narcolepsy patients with or without cataplexy. Main outcome
      measures were: rapid eye movement sleep behaviour disorder symptoms; short and
      long muscle activations per hour rapid eye movement and non-rapid eye movement
      sleep; and periodic and non-periodic limb movements per hour rapid eye movement
      and non-rapid eye movement sleep. Outcome variables were analysed in relation to
      cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear
      regression models, controlling for possible rapid eye movement sleep behaviour
      disorder biasing factors (age, gender, disease duration, previous anti-cataplexy
      medication). Only hypocretin deficiency independently predicted rapid eye
      movement sleep behaviour disorder symptoms (relative risk = 3.69, P = 0.03), long
      muscle activations per hour rapid eye movement sleep (ln-coefficient = 0.81, P <
      0.01), and short muscle activations per hour rapid eye movement sleep (ln
      coefficient = 1.01, P < 0.01). Likewise, periodic limb movements per hour rapid
      eye movement and non-rapid eye movement sleep were only associated with
      hypocretin deficiency (P < 0.01). A significant association between hypocretin
      deficiency and cataplexy was confirmed (P < 0.01). In a sub-analysis, hypocretin
      deficiency suggested the association of periodic limb movements and rapid eye
      movement sleep behaviour disorder outcomes (symptoms, non-periodic short and long
      muscle activity) in rapid eye movement sleep. Our results support the hypothesis
      that hypocretin deficiency is independently associated with rapid eye movement
      sleep behaviour disorder in narcolepsy. Thus, hypocretin deficiency is linked to
      the two major disturbances of rapid eye movement sleep motor regulation in
      narcolepsy: rapid eye movement sleep behaviour disorder and cataplexy. Hypocretin
      deficiency is also significantly associated with periodic limb movements in rapid
      eye movement and non-rapid eye movement sleep, and provides a possible
      pathophysiological link between rapid eye movement sleep behaviour disorder and
      periodic limb movements in narcolepsy. The study supports the hypothesis that an
      impaired hypocretin system causes a general instability of motor regulation
      during wakefulness, rapid eye movement and non-rapid eye movement sleep in human
      narcolepsy.

PMID- 20129933
TI  - Novel forms of neurofascin 155 in the central nervous system: alterations in
      paranodal disruption models and multiple sclerosis.
AB  - Stability of the myelin-axon unit is achieved, at least in part, by specialized
      paranodal junctions comprised of the neuronal heterocomplex of contactin and
      contactin-associated protein and the myelin protein neurofascin 155. In multiple
      sclerosis, normal distribution of these proteins is altered, resulting in the
      loss of the insulating myelin and consequently causing axonal dysfunction.
      Previously, this laboratory reported that mice lacking the myelin-enriched lipid
      sulphatide are characterized by a progressive deterioration of the paranodal
      structure. Here, it is shown that this deterioration is preceded by significant
      loss of neurofascin 155 clustering at the myelin paranode. Interestingly,
      prolonged electrophoretic separation revealed the existence of two neurofascin
      155 bands, neurofascin 155 high and neurofascin 155 low, which are readily
      observed following N-linked deglycosylation. Neurofascin 155 high is observed at
      7 days of age and reaches peak expression at one month of age, while neurofascin
      155 low is first observed at 14 days of age and constantly increases until 5
      months of age. Studies using conditional neurofascin knockout mice indicated that
      neurofascin 155 high and neurofascin 155 low are products of the neurofascin gene
      and are exclusively expressed by oligodendrocytes within the central nervous
      system. Neurofascin 155 high is a myelin paranodal protein while the distribution
      of neurofascin 155 low remains to be determined. While neurofascin 155 high
      levels are significantly reduced in the sulphatide null mice at 15 days, 30 days
      and 4 months of age, neurofascin 155 low levels remain unaltered. Although
      maintained at normal levels, neurofascin 155 low is incapable of preserving
      paranodal structure, thus indicating that neurofascin 155 high is required for
      paranodal stability. Additionally, comparisons between neurofascin 155 high and
      neurofascin 155 low in human samples revealed a significant alteration,
      specifically in multiple sclerosis plaques.

PMID- 20129935
TI  - Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic
      spectrum of a treatable disorder.
AB  - Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1
      gene in the majority of patients and results in impaired glucose transport into
      the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1
      gene were studied by automated Sanger sequencing and multiplex ligation-dependent
      probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients
      (41%) and subsequently in three clinically affected family members. In these 57
      patients we identified 49 different mutations, including six multiple exon
      deletions, six known mutations and 37 novel mutations (13 missense, five
      nonsense, 13 frame shift, four splice site and two translation initiation
      mutations). Clinical data were retrospectively collected from referring
      physicians by means of a questionnaire. Three different phenotypes were
      recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2
      years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental
      retardation and movement disorder, without epilepsy (15%); and (iii) one adult
      case of glucose transporter-1 deficiency syndrome with minimal symptoms.
      Recognizing glucose transporter-1 deficiency syndrome is important, since a
      ketogenic diet was effective in most of the patients with epilepsy (86%) and also
      reduced movement disorders in 48% of the patients with a classical phenotype and
      71% of the patients with a non-classical phenotype. The average delay in
      diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years
      (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range
      0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was
      below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate
      was low to normal in all patients. Our relatively large series of 57 patients
      with glucose transporter-1 deficiency syndrome allowed us to identify
      correlations between genotype, phenotype and biochemical data. Type of mutation
      was related to the severity of mental retardation and the presence of complex
      movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type
      of mutation and phenotype. In conclusion, a substantial number of the patients
      with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study
      demonstrates that a lumbar puncture provides the diagnostic clue to glucose
      transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic
      delay to allow early start of the ketogenic diet.

PMID- 20129937
TI  - Acute disseminated encephalomyelitis and multiple sclerosis.

PMID- 20129936
TI  - Optimized adeno-associated viral vector-mediated striatal DOPA delivery restores
      sensorimotor function and prevents dyskinesias in a model of advanced Parkinson's
      disease.
AB  - Viral vector-mediated gene transfer utilizing adeno-associated viral vectors has
      recently entered clinical testing as a novel tool for delivery of therapeutic
      agents to the brain. Clinical trials in Parkinson's disease using adeno
      associated viral vector-based gene therapy have shown the safety of the approach.
      Further efforts in this area will show if gene-based approaches can rival the
      therapeutic efficacy achieved with the best pharmacological therapy or other,
      already established, surgical interventions. One of the strategies under
      development for clinical application is continuous 3,4-dihydroxyphenylalanine
      delivery. This approach has been shown to be efficient in restoring motor
      function and reducing established dyskinesias in rats with a partial lesion of
      the nigrostriatal dopamine projection. Here we utilized high purity recombinant
      adeno-associated viral vectors serotype 5 coding for tyrosine hydroxylase and its
      co-factor synthesizing enzyme guanosine-5'-triphosphate cyclohydrolase-1,
      delivered at an optimal ratio of 5 : 1, to show that the enhanced 3,4
      dihydroxyphenylalanine production obtained with this optimized delivery system
      results in robust recovery of function in spontaneous motor tests after complete
      dopamine denervation. We found that the therapeutic efficacy was substantial and
      could be maintained for at least 6 months. The tyrosine hydroxylase plus
      guanosine-5'-triphosphate cyclohydrolase-1 treated animals were resistant to
      developing dyskinesias upon peripheral l-3,4-dihydroxyphenylalanine drug
      challenge, which is consistent with the interpretation that continuous dopamine
      stimulation resulted in a normalization of the post-synaptic response.
      Interestingly, recovery of forelimb use in the stepping test observed here was
      maintained even after a second lesion depleting the serotonin input to the
      forebrain, suggesting that the therapeutic efficacy was not solely dependent on
      dopamine synthesis and release from striatal serotonergic terminals. Taken
      together these results show that vector-mediated continuous 3,4
      dihydroxyphenylalanine delivery has the potential to provide significant
      symptomatic relief even in advanced stages of Parkinson's disease.

PMID- 20129938
TI  - Patient costs for paediatric hospital admissions in Tanzania: a neglected burden?
AB  - OBJECTIVE: Tanzania has a policy of free provision of inpatient care for young
      children in order to promote timely access and thus reduce the current levels of
      mortality. However, little is known about out-of-pocket costs that may be
      incurred by families in seeking care for sick children. We conducted this study
      to identify the magnitude of these costs in relation to family income. METHODS:
      Five hundred and ten caretakers were interviewed on the day of discharge of their
      child from 11 hospitals in north-east Tanzania. Caretakers were asked to report
      expenditure related to hospitalization in various categories and family wealth
      was assessed through reported expenditure in the previous month. RESULTS: Food
      (mean US$2.2, median US$1.6), transport (mean US$1.7, median US$0) and medicines
      (mean US$1.0, median US$0.4) were the leading categories of expenditure, and
      overall the mean out-of-pocket expenditure was US$5.5 (median US$3.7) per
      admission. Mean out-of-pocket expenditure was more than 1.5 times higher for
      households in the highest monthly expenditure quintile compared with those in the
      lowest. However, this differential was reversed when expenditure was considered
      as a proportion of family expenditure in the previous month; for the lowest
      quintile, families spent more than three-quarters of their total monthly
      expenditure on a single paediatric admission. CONCLUSION: Out-of-pocket
      expenditure on child hospitalization places a considerable burden on poor
      families. Our findings justify a closer scrutiny of how this expenditure could be
      reduced, particularly through the provision of adequate food for both children
      and caretakers and through reducing stock-outs of essential medicines.

PMID- 20129939
TI  - Deep SAGE analysis of the Caenorhabditis elegans transcriptome.
AB  - We employed the Tag-seq technique to generate global transcription profiles for
      different strains and life stages of the nematode C. elegans. Tag-seq generates
      cDNA tags as does Serial Analysis of Gene Expression (SAGE), but the method
      yields a much larger number of tags, generating much larger data sets than SAGE.
      We examined differences in the performance of SAGE and Tag-seq by comparing gene
      expression data for 13 pairs of libraries. We identified genes for which
      expression was consistently changed in long-lived worms. Additional genes emerged
      in the deeper Tag-seq profiles, including several 'signature' genes found among
      those zup-regulated in long-lived dauer larvae (cki-1, aak-2 and daf-16). Fifty
      to sixty percent of the genes differentially expressed in daf-2(-) versus daf
      2(+) adults had fragmentary or no functional annotation, suggesting the
      involvement of as yet unstudied pathways in aging. We were able to distinguish
      between changes in gene expression associated with altered genotype or altered
      growth conditions. We found 62 cases of possible mRNA isoform switching in the 13
      Tag-seq libraries, whereas the 13 SAGE libraries allowed detection of only 15
      such occurrences. We observed strong expression of anti-sense transcripts for
      several mitochondrial genes, but nuclear anti-sense transcripts were neither
      abundant nor consistently expressed among the libraries.

PMID- 20129940
TI  - Promoter chromatin remodeling of immediate-early genes is mediated through H3
      phosphorylation at either serine 28 or 10 by the MSK1 multi-protein complex.
AB  - Upon activation of the ERK and p38 MAPK pathways, the MSK1/2-mediated nucleosomal
      response, including H3 phosphorylation at serine 28 or 10, is coupled with the
      induction of immediate-early (IE) gene transcription. The outcome of this
      response, varying with the stimuli and cellular contexts, ranges from neoplastic
      transformation to neuronal synaptic plasticity. Here, we used sequential co
      immunoprecipitation assays and sequential chromatin immunoprecipitation (ChIP)
      assays on mouse fibroblast 10T1/2 and MSK1 knockdown 10T1/2 cells to show that H3
      serine 28 and 10 phosphorylation leads to promoter remodeling. MSK1, in complexes
      with phospho-serine adaptor 14-3-3 proteins and BRG1 the ATPase subunit of the
      SWI/SNF remodeler, is recruited to the promoter of target genes by transcription
      factors such as Elk-1 or NF-kappaB. Following MSK1-mediated H3 phosphorylation,
      BRG1 associates with the promoter of target genes via 14-3-3 proteins, which act
      as scaffolds. The recruited SWI/SNF remodels nucleosomes at the promoter of IE
      genes enabling the binding of transcription factors like JUN and the onset of
      transcription.

PMID- 20129941
TI  - A novel antisense RNA regulates at transcriptional level the virulence gene icsA
      of Shigella flexneri.
AB  - The virulence gene icsA of Shigella flexneri encodes an invasion protein crucial
      for host colonization by pathogenic bacteria. Within the intergenic region virA
      icsA, we have discovered a new gene that encodes a non-translated antisense RNA
      (named RnaG), transcribed in cis on the complementary strand of icsA. In vitro
      transcription assays show that RnaG promotes premature termination of
      transcription of icsA mRNA. Transcriptional inhibition is also observed in vivo
      by monitoring the expression profile in Shigella by real-time polymerase chain
      reaction and when RnaG is provided in trans. Chemical and enzymatic probing of
      the leader region of icsA mRNA either free or bound to RnaG indicate that upon
      hetero-duplex formation an intrinsic terminator, leading to transcription block,
      is generated on the nascent icsA mRNA. Mutations in the hairpin structure of the
      proposed terminator impair the RnaG mediated-regulation of icsA transcription.
      This study represents the first evidence of transcriptional attenuation mechanism
      caused by a small RNA in Gram-negative bacteria. We also present data on the
      secondary structure of the antisense region of RnaG. In addition, alternatively
      silencing icsA and RnaG promoters, we find that transcription from the strong
      RnaG promoter reduces the activity of the weak convergent icsA promoter through
      the transcriptional interference regulation.

PMID- 20129942
TI  - The structure of DdrB from Deinococcus: a new fold for single-stranded DNA
      binding proteins.
AB  - Deinococcus spp. are renowned for their amazing ability to recover rapidly from
      severe genomic fragmentation as a result of exposure to extreme levels of
      ionizing radiation or desiccation. Despite having been originally characterized
      over 50 years ago, the mechanism underlying this remarkable repair process is
      still poorly understood. Here, we report the 2.8 A structure of DdrB, a single
      stranded DNA (ssDNA) binding protein unique to Deinococcus spp. that is crucial
      for recovery following DNA damage. DdrB forms a pentameric ring capable of
      binding single-stranded but not double-stranded DNA. Unexpectedly, the crystal
      structure reveals that DdrB comprises a novel fold that is structurally and
      topologically distinct from all other single-stranded binding (SSB) proteins
      characterized to date. The need for a unique ssDNA binding function in response
      to severe damage, suggests a distinct role for DdrB which may encompass not only
      standard SSB protein function in protection of ssDNA, but also more specialized
      roles in protein recruitment or DNA architecture maintenance. Possible mechanisms
      of DdrB action in damage recovery are discussed.

PMID- 20129943
TI  - Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.
AB  - The REF/ALY mRNA export adaptor binds TAP/NXF1 via an arginine-rich region, which
      overlaps with its RNA-binding domain. When TAP binds a REF:RNA complex, it
      triggers transfer of the RNA from REF to TAP. Here, we have examined the effects
      of arginine methylation on the activities of the REF protein in mRNA export. We
      have mapped the arginine methylation sites of REF using mass spectrometry and
      find that several arginines within the TAP and RNA binding domains are methylated
      in vivo. However, arginine methylation has no effect on the REF:TAP interaction.
      Instead, arginine methylation reduces the RNA-binding activity of REF in vitro
      and in vivo. The reduced RNA-binding activity of REF in its methylated state is
      essential for efficient displacement of RNA from REF by TAP in vivo. Therefore,
      arginine methylation fine-tunes the RNA-binding activity of REF such that the RNA
      protein interaction can be readily disrupted by export factors further down the
      pathway.

PMID- 20129944
TI  - Force spectroscopy and fluorescence microscopy of dsDNA-YOYO-1 complexes:
      implications for the structure of dsDNA in the overstretching region.
AB  - When individual dsDNA molecules are stretched beyond their B-form contour length,
      they reveal a structural transition in which the molecule extends 1.7 times its
      contour length. The nature of this transition is still a subject of debate. In
      the first model, the DNA helix unwinds and combined with the tilting of the base
      pairs (which remain intact), results in a stretched form of DNA (also known as S
      DNA). In the second model the base pairs break resulting effectively in two
      single-strands, which is referred to as force-induced melting. Here a combination
      of optical tweezers force spectroscopy with fluorescence microscopy was used to
      study the structure of dsDNA in the overstretching regime. When dsDNA was
      stretched in the presence of 10 nM YOYO-1 an initial increase in total
      fluorescence intensity of the dye-DNA complex was observed and at an extension
      where the dsDNA started to overstretch the fluorescence intensity leveled off and
      ultimately decreased when stretched further into the overstretching region.
      Simultaneous force spectroscopy and fluorescence polarization microscopy revealed
      that the orientation of dye molecules did not change significantly in the
      overstretching region (78.0 degrees +/- 3.2 degrees). These results presented
      here clearly suggest that, the structure of overstretched dsDNA can be explained
      accurately by force induced melting.

PMID- 20129945
TI  - The value of serial plasma nuclear and mitochondrial DNA levels in adult
      community-acquired bacterial meningitis.
AB  - BACKGROUND: Increased levels of plasma nuclear and mitochondrial DNA have been
      reported in critically ill patients. We tested the hypothesis that plasma nuclear
      and mitochondrial DNA are substantially increased in acute bacterial meningitis
      and decrease after antimicrobial therapy, and that plasma nuclear and
      mitochondrial DNA levels can predict treatment outcomes. METHODS: We examined
      serial plasma nuclear and mitochondrial DNA levels in 22 adult community-acquired
      bacterial meningitis (ACABM) patients. The plasma nuclear and mitochondrial DNA
      levels were also evaluated in 11 aseptic meningitis patients and 22 volunteer
      subjects during the study period. RESULTS: All of the both bacterial and aseptic
      meningitis groups had a higher plasma DNA levels on admission as compared with
      those of volunteer groups. Levels of plasma nuclear and mitochondrial DNA in
      ACABM cases were significantly increased initially and substantially decreased
      thereafter. Both plasma nuclear DNA and plasma mitochondrial DNA levels at
      presentation are significantly negative correlate with modified Barthel Index
      (average) (r = -0.639, P = 0.004 and r = -0.551, P = 0.018) at 3 months after
      discharge (average), respectively, in this study. Both higher plasma nuclear
      (cutoff value of >169 ng/ml) and mitochondrial DNA levels (cutoff value of >58.9
      ng/ml) at presentation were associated with poor outcome in ACABM patients.
      CONCLUSION: Based on our results, the higher plasma DNA levels were associated
      with a poorer outcome. Therefore, we look forward to more prospective multicenter
      investigations specifically to confirm the predictive value of plasma DNA levels
      in outcome prediction.

PMID- 20129946
TI  - Taqman real-time quantitative PCR for identification of western flower thrip
      (Frankliniella occidentalis) for plant quarantine.
AB  - Western flower thrip (Frankliniella occidentalis) is a major global pest of
      agricultural products. It directly damages crops through feeding, oviposition
      activity or transmission of several plant viruses. We describe a Taqman real-time
      quantitative PCR detection system, which can rapidly identify F. occidentalis
      from thrips larvae to complement the traditional morphological identification.
      The data showed that our detection system targeted on the ribosomal RNA gene
      regions of F. occidentalis has high sensitivity and specificity. The rapid method
      can be used for on-site testing of samples at ports-of-entry in the future.

PMID- 20129947
TI  - Vortex interactions with flapping wings and fins can be unpredictable.
AB  - As they fly or swim, many animals generate a wake of vortices with their flapping
      fins and wings that reveals the dynamics of their locomotion. Previous studies
      have shown that the dynamic interaction of vortices in the wake with fins and
      wings can increase propulsive force. Here, we explore whether the dynamics of the
      vortex interactions could affect the predictability of propulsive forces. We
      studied the dynamics of the interactions between a symmetrically and periodically
      pitching and heaving foil and the vortices in its wake, in a soap-film tunnel.
      The phase-locked movie sequences reveal that abundant chaotic vortex-wake
      interactions occur at high Strouhal numbers. These high numbers are
      representative for the fins and wings of near-hovering animals. The chaotic wake
      limits the forecast horizon of the corresponding force and moment integrals. By
      contrast, we find periodic vortex wakes with an unlimited forecast horizon for
      the lower Strouhal numbers (0.2-0.4) at which many animals cruise. These findings
      suggest that swimming and flying animals could control the predictability of
      vortex-wake interactions, and the corresponding propulsive forces with their fins
      and wings.

PMID- 20129948
TI  - Conformist learning in nine-spined sticklebacks' foraging decisions.
AB  - Theoretical analyses have reported that in most circumstances where natural
      selection favours reliance on social learning, conformity (positive frequency
      dependent social learning) is also favoured. These findings suggest that much
      animal social learning should involve a copy-the-majority strategy, yet there is
      currently surprisingly little evidence for conformist learning among animals.
      Here, we investigate this possibility in the nine-spined stickleback (Pungitius
      pungitius) by manipulating the number of demonstrator fish at two feeders, one
      rich and one poor, during a demonstration phase and evaluating how this affects
      the likelihood that the focal fish copy the demonstrators' apparent choices. As
      predicted, we observed a significantly increased level of copying with increasing
      numbers of demonstrators at the richer of the two feeders, with copying
      increasing disproportionately, rather than linearly, with the proportion of
      demonstrators at the rich foraging patch. Control conditions with non-feeding
      demonstrators showed that this was not simply the result of a preference for
      shoaling with larger groups, implying that nine-spined sticklebacks copy in a
      conformist manner.

PMID- 20129949
TI  - The presence of an avian co-forager reduces vigilance in a cooperative mammal.
AB  - Many animals must trade-off anti-predator vigilance with other behaviours. Some
      species facilitate predator detection by joining mixed-species foraging parties
      and 'eavesdropping' on the predator warnings given by other taxa. Such use of
      heterospecific warnings presumably reduces the likelihood of predation, but it is
      unclear whether it also provides wider benefits, by allowing individuals to
      reduce their own vigilance. We examine whether the presence of an avian co
      forager, the fork-tailed drongo (Dicrurus adsimilis), affects rates of vigilance
      (including sentinel behaviour) in wild dwarf mongooses (Helogale parvula). We
      simulate the presence of drongos-using playbacks of their non-alarm vocalizations
      to show that dwarf mongooses significantly reduce their rate of vigilance when
      foraging with this species. This is, to our knowledge, the first study to
      demonstrate experimentally that a mammal reduces vigilance in the presence of an
      avian co-forager.

PMID- 20129950
TI  - Double cones are used for colour discrimination in the reef fish, Rhinecanthus
      aculeatus.
AB  - Double cones (DCs) are the most common cone types in fish, reptiles and birds. It
      has been suggested that DCs are used for achromatic tasks such as luminance,
      motion and polarization vision. Here we show that a reef fish Rhinecanthus
      aculeatus can discriminate colours on the basis of the difference between the
      signals of individual members of DCs. This is the first direct evidence that
      individual members of DCs are used in colour vision as independent spectral
      channels.

PMID- 20129951
TI  - Fluctuating feather asymmetry in relation to corticosterone levels is sex
      dependent in Eurasian treecreeper (Certhia familiaris) nestlings.
AB  - Fluctuating asymmetry (FA) has been widely used as a stress-related phenotypic
      marker of developmental instability. However, previous studies relating FA to
      various stressful conditions have produced inconsistent results and we still lack
      quantitative individual-level evidence that high FA is related to stress in wild
      vertebrate species. We studied how baseline plasma levels of corticosterone
      predicted FA of wing and tail feathers in free-living Eurasian treecreeper
      (Certhia familiaris) nestlings. We found a sex-specific association between
      corticosterone levels and FA: high corticosterone levels were related to an
      increased FA in male but not in female nestlings. These results suggest that in
      treecreepers, FA may correlate with individual stress hormone levels, male
      developmental trajectory being potentially more sensitive to stress than that of
      the female.

PMID- 20129952
TI  - Do toads have a jump on how far they hop? Pre-landing activity timing and
      intensity in forelimb muscles of hopping Bufo marinus.
AB  - During jumping or falling in humans and various other mammals, limb muscles are
      activated before landing, and the intensity and timing of this pre-landing
      activity are scaled to the expected impact. In this study, we test whether
      similarly tuned anticipatory muscle activity is present in hopping cane toads.
      Toads use their forelimbs for landing, and we analysed pre-landing
      electromyographic (EMG) timing and intensity in relation to hop distance for the
      m. coracoradialis and m. anconeus, which act antagonistically at the elbow, and
      are presumably important in stabilizing the forelimb during landing. In most
      cases, a significant, positive relationship between hop distance and pre-landing
      EMG intensity was found. Moreover, pre-landing activation timing of m. anconeus
      was tightly linked to when the forelimbs touched down at landing. Thus, like
      mammals, toads appear to gauge the timing and magnitude of their impending impact
      and activate elbow muscles accordingly. To our knowledge these data represent the
      first demonstration of tuned pre-landing muscle recruitment in anurans and raise
      questions about how important the visual, vestibular and/or proprioceptive
      systems are in mediating this response.

PMID- 20129954
TI  - Magnetoreception.

PMID- 20129953
TI  - Photoreceptor-based magnetoreception: optimal design of receptor molecules,
      cells, and neuronal processing.
AB  - The sensory basis of magnetoreception in animals still remains a mystery. One
      hypothesis of magnetoreception is that photochemical radical pair reactions can
      transduce magnetic information in specialized photoreceptor cells, possibly
      involving the photoreceptor molecule cryptochrome. This hypothesis triggered a
      considerable amount of research in the past decade. Here, we present an updated
      picture of the radical-pair photoreceptor hypothesis. In our review, we will
      focus on insights that can assist biologists in their search for the elusive
      magnetoreceptors.

PMID- 20129955
TI  - Micronucleus-centromere assay in workers occupationally exposed to low level of
      benzene.
AB  - Benzene is a well-known carcinogen that induces chromosomal instability,
      including chromosome aberration and aneuploidy. In order to assess aneugenic
      effect of low-level benzene, micronucleus-centromere assay using specific probes
      for chromosomes 7 and 9 was performed in workers occupationally exposed to low
      dose benzene at a petroleum refinery. A micronucleus-centromere assay using a pan
      centromeric probe was also performed to determine the origin of benzene-induced
      micronucleus (MN). Frequency of aneuploidy of chromosomes 7 and 9 was
      significantly higher among workers compared to the unexposed control group.
      Poisson regression analysis revealed that aneuploidy frequency of chromosome 7 or
      9 was significantly associated with benzene level after adjusting for confounding
      variables such as age, smoking, alcohol intake, and duration of work (p = .042).
      Additionally, frequencies of MN and centromere-negative micronuclei (MNC-) were
      significantly higher in benzene-exposed workers compared to controls, while
      frequency of centromere-positive micronuclei (MNC+) was similar in both groups.
      In conclusion, aneuploidy of chromosomes 7 and 9 could be a useful biomarker to
      assess the effect of low-level benzene exposure, and benzene-induced MN
      originates from chromosome breaks rather than chromosome non-disjunction.

PMID- 20129956
TI  - Prompt and successful toxin-targeting treatment of three patients with
      necrotizing pneumonia due to Staphylococcus aureus strains carrying the Panton
      Valentine leukocidin genes.
AB  - Three patients with extensive necrotizing pneumonia due to Panton-Valentine
      leukocidin-positive Staphylococcus aureus strains and with aggravating factors
      (leukopenia count of less than 3x10(9)/liter in all three cases and hemoptysis in
      two cases) were successfully treated with toxin-suppressing agents introduced
      rapidly after hospital admission.

PMID- 20129957
TI  - Outbreak of febrile respiratory illness associated with adenovirus 11a infection
      in a Singapore military training cAMP.
AB  - Outbreak cases of acute respiratory disease (ARD) associated with subspecies B2
      human adenovirus 11a (HAdV-11a) infection were detected during 2005 in a military
      basic training camp in Singapore. The Singapore HAdV-11a strain is highly similar
      to other Asian strains of HAdV-11, including strain QS-DLL, which is responsible
      for the recently described 2006 outbreak of ARD in China.

PMID- 20129958
TI  - Low prevalence rate of indeterminate serological human immunodeficiency virus
      results among pregnant women from Burkina Faso, West Africa.
AB  - Rapid human immunodeficiency virus (HIV) antibody tests have been adopted into
      national guidelines for HIV testing in many countries in sub-Saharan Africa. One
      goal of HIV rapid testing is to minimize the occurrence of indeterminate results.
      From January 2005 to December 2007, plasma (or serum) samples from pregnant women
      in Bobo-Dioulasso (Burkina Faso, West Africa) were screened for HIV by using two
      rapid tests (the Determine HIV1/2 test [Abbott] and Genie II HIV-1/HIV-2 [Bio
      Rad]) through a sequential algorithm prior to enrollment of HIV-1-infected women
      in a prevention of mother-to-child transmission (PMTCT) trial (WHO/ANRS 1289
      Kesho Bora trial). Samples exhibiting indeterminate results (Determine positive
      and Genie II negative) were further tested with a fourth-generation HIV enzyme
      immunoassay (EIA) (Murex HIV Ag/Ab combination in 2005 and 2006 and Vironostika
      HIV Uni-Form II Ag/Ab in 2007). If positive, they were finally assessed for HIV-1
      RNA (Generic HIV-1 RNA viral load assay; Biocentric). From a total of 44,653
      samples tested, 597 (1.3%) showed indeterminate results. Of these, 367 could be
      analyzed by EIA. Only 15 (15/367, 4.1%) samples were found EIA reactive. Of
      these, 11 could be tested for HIV-1 RNA. All were HIV-1 RNA negative. In our
      clinical practice, pregnant women with such indeterminate results are now
      reassured during posttest counseling that they are very unlikely to be infected
      with HIV-1. As a consequence, such women with indeterminate results can reliably
      be considered negative when urgent clinical decisions (such as providing PMTCT
      prophylaxis) need to be taken.

PMID- 20129959
TI  - Identification of clinically important anaerobic bacteria by an oligonucleotide
      array.
AB  - Anaerobic bacteria can cause a wide variety of infections, and some of these
      infections can be serious. Conventional identification methods based on
      biochemical tests are often lengthy and can produce inconclusive results. An
      oligonucleotide array based on the 16S-23S rRNA intergenic spacer (ITS) sequences
      was developed to identify 28 species of anaerobic bacteria and Veillonella. The
      method consisted of PCR amplification of the ITS regions with universal primers,
      followed by hybridization of the digoxigenin-labeled PCR products to a panel of
      35 oligonucleotide probes (17- to 30-mers) immobilized on a nylon membrane. The
      performance of the array was determined by testing 310 target strains (strains
      which we aimed to identify), including 122 reference strains and 188 clinical
      isolates. In addition, 98 nontarget strains were used for specificity testing.
      The sensitivity and the specificity of the array for the identification of pure
      cultures were 99.7 and 97.1%, respectively. The array was further assessed for
      its ability to detect anaerobic bacteria in 49 clinical specimens. Two species
      (Finegoldia magna and Bacteroides vulgatus) were detected in two specimens by the
      array, and the results were in accordance with those obtained by culture. The
      whole procedure of array hybridization took about 8 h, starting with the isolated
      colonies. The array can be used as an accurate alternative to conventional
      methods for the identification of clinically important anaerobes.

PMID- 20129960
TI  - Full-genome sequence analysis of a multirecombinant echovirus 3 strain isolated
      from sewage in Greece.
AB  - An echovirus 3 (Echo3) strain (strain LR31G7) was isolated from a sewage
      treatment plant in Greece in 2005. Full-genome molecular, phylogenetic, and
      SimPlot analyses were conducted in order to reveal the evolutionary pathways of
      the isolate. Nucleotide and phylogenetic analyses of part of the VP1 genomic
      region revealed that the isolated strain correlates with Echo3 strains isolated
      during the same year in France and Japan, implying that the same virus circulated
      in Europe and Asia. LR31G7 was found to be a recombinant that shares the 3' part
      of its genome with an Echo25 strain isolated from asymptomatic infants in Norway
      in 2003. Nucleotide and SimPlot analyses of the VP1-2A junction, where the
      recombination was located, revealed the exact recombination breakpoint
      (nucleotides 3357 to 3364). Moreover, there is evidence that recombination events
      had occurred in 3B-3D region in the evolutionary history of the isolate. Our
      study indicates that recombination events play major roles in enterovirus
      evolution and that the circulation of multirecombinant strains with unknown
      properties could be potentially dangerous for public health.

PMID- 20129961
TI  - Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza
      A/H1N1 viruses.
AB  - The emergence and widespread occurrence of antiviral drug-resistant seasonal
      human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are
      major concerns. To understand the genetic background of antiviral drug-resistant
      A/H1N1 viruses, we performed full genome sequencing of prepandemic A/H1N1
      strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible
      viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses,
      obtained from several areas in Japan during the 2007-2008 and 2008-2009 influenza
      seasons were analyzed. Sequencing of the full genomes of these viruses was
      performed, and the phylogenetic relationships among the sequences of each
      individual genome segment were inferred. Reference genome sequences from the
      Influenza Virus Resource database were included to determine the closest ancestor
      for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant
      strain evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which
      circulated in the 2007-2008 season by acquiring the H275Y resistance-conferring
      mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the
      Northern European resistant lineage) represented 100% of the H1N1 isolates from
      the 2008-2009 season and further acquired at least one mutation in each of the
      polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin
      (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two
      distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in
      the NA gene and other mutations elsewhere in the genome, contributed to the
      emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant
      viruses from the 2007-2008 season distinctly clustered in clade 2C and were
      characterized by extensive amino acid substitutions across their genomes,
      suggesting that a fitness gap among its genetic components might have driven
      these mutations to maintain it in the population.

PMID- 20129962
TI  - Molecular characterization of an adenovirus 3-16 intertypic recombinant isolated
      in Argentina from an infant hospitalized with acute respiratory infection.
AB  - An intertypic recombinant adenovirus with a serotype 3-like hexon gene and a
      serotype 16-like fiber (99% identical to that of the prototype strain of human
      adenovirus 16 [HAdV-16], Ch79) was isolated in Argentina from an infant admitted
      to the hospital with acute respiratory disease. Consistent with the results of
      molecular characterization, strain Arg827/04 was designated H3-F16.

PMID- 20129963
TI  - Antifungal susceptibility testing of Candida isolates from the Candida
      surveillance study.
AB  - Candida species are a common cause of nosocomial bloodstream infections. Recent
      surveillance has shown an increase in the relative proportion of infections
      caused by Candida glabrata, which has reduced susceptibility to fluconazole. We
      undertook sentinel surveillance with antifungal susceptibility testing to monitor
      the trends in the proportions of various Candida species causing invasive
      disease. Forty-one institutions participated in the Candida Surveillance Study.
      All isolates were submitted to a central laboratory for identification and
      susceptibility testing. Susceptibility testing was performed in compliance with
      CLSI guidelines using a custom, broth dilution, microtiter system. There were
      5,900 isolates submitted for identification and antifungal susceptibility
      testing. The distribution of species was as follows: C. albicans, 2,567 (43.5%)
      isolates; C. glabrata, 1,464 (24.8%) isolates; C. parapsilosis, 1,048 (17.8%)
      isolates; C. tropicalis, 527 (8.9%) isolates; C. krusei, 109 (1.9%) isolates; C.
      lusitaniae, 76 (1.3%) isolates; and other Candida species, 109 (1.9%) isolates.
      Resistance to fluconazole occurred in 1.2% of C. albicans isolates, 5.9% of C.
      glabrata isolates, 0.3% of C. parapsilosis isolates, and 0.4% of C. tropicalis
      isolates. Resistance to fluconazole was highly predictive of resistance to
      voriconazole. Resistance to echinocandins was rarely found, occurring in only
      0.2% of all isolates. The rate of fluconazole susceptibility increased
      significantly from 87.5% in 2005 to 97.4% in 2007. The proportion of cases of
      disease caused by various Candida species did not change appreciably between 2004
      and 2007, and the rate of antifungal susceptibility was high.

PMID- 20129964
TI  - Evaluation of an upgraded version of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1
      test for HIV-1 load quantification.
AB  - We evaluated the performance of the prototype Cobas AmpliPrep/Cobas TaqMan HIV-1
      test, version 2.0, using prospective and archived clinical samples initially
      underquantitated by the Cobas AmpliPrep/Cobas TaqMan HIV-1 test. The performance
      of the new test was significantly improved, and the majority of the
      underquantitation observed with the first-version test was eliminated.

PMID- 20129965
TI  - Direct detection of methicillin resistance in Staphylococcus aureus in blood
      culture broth by use of a penicillin binding protein 2a latex agglutination test.
AB  - We studied the utility of performing a penicillin binding protein 2a latex
      agglutination (PBP-LA) assay directly on Bactec blood culture broth samples
      containing Staphylococcus aureus to rapidly detect methicillin resistance. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value of this method were 94.1%, 97.5%, 98%, and 92.9%, respectively.

PMID- 20129966
TI  - Rapid and direct quantification of viable Candida species in whole blood by use
      of immunomagnetic separation and solid-phase cytometry.
AB  - Candida species are a common source of nosocomial bloodstream infections in
      critically ill patients. The sensitivity of the traditional diagnostic procedure
      based on blood culture is variable, and it usually takes 2 to 4 days before
      growth of Candida species is detected. We developed a 4-h method for the
      quantification of Candida species in blood, combining immunomagnetic separation
      (IMS) with solid-phase cytometry (SPC) using viability labeling. Additionally,
      Candida albicans cells could be identified in real time by using fluorescent in
      situ hybridization. By analysis of spiked blood samples, our method was shown to
      be sensitive and specific, with a low detection limit (1 cell/ml of blood). In a
      proof-of-concept study, we applied the IMS/SPC method to 16 clinical samples and
      compared it to traditional blood culture. Our method proved more sensitive than
      culture (seven samples were positive with IMS/SPC but negative with blood
      culture), and identification results were in agreement. The IMS/SPC data also
      suggest that mixed infections might occur frequently, as C. albicans and at least
      one other Candida species were found in five samples. Additionally, in two cases,
      high numbers of cells (175 to 480 cells/ml of blood) were associated with an
      endovascular source of infection.

PMID- 20129967
TI  - Scrub typhus in previously unrecognized areas of endemicity in China.
AB  - Scrub typhus, caused by Orientia tsutsugamushi, has emerged recently in areas of
      northern China where the disease had not been known to exist. We analyzed
      epidemiological, clinical, and laboratory data for 104 patients who were admitted
      to a hospital in Fuyang City between 26 September and 1 November 2008. We showed
      that the major clinical manifestations of the patients were fever (100%),
      headache (82%), myalgias (77%), eschar (67%), rash (52%), and unusual facial
      flushing (62%). Among the 104 patients, the sera of 98% contained IgM antibodies
      to O. tsutsugamushi detected by indirect immunofluorescence assays (IFA), and DNA
      of the O. tsutsugamushi 56-kDa gene was amplified by PCR from the blood of 36
      patients. We conclude that 104 patients were infected with scrub typhus in Fuyang
      City, Anhui Province. Our study indicates that physicians need to consider the
      diagnosis of scrub typhus for febrile patients living in northern China, where
      scrub typhus had not been considered to exist in the past.

PMID- 20129968
TI  - Novel real-time PCR assay for simultaneous detection and differentiation of
      Clostridium chauvoei and Clostridium septicum in clostridial myonecrosis.
AB  - A real-time PCR assay based on the 16S rRNA gene sequence was designed for
      differentiation of blackleg-causing Clostridium chauvoei and Clostridium
      septicum, a phylogenetically closely related bacterium responsible for malignant
      edema. In order to exclude false-negative results, an internal amplification
      control was included in the assay. A set of three probes, one specific for C.
      chauvoei, one specific for C. septicum, and one specific for both species,
      permitted unequivocal detection of C. chauvoei in tests of 32 Clostridium sp.
      strains and 10 non-Clostridium strains. The assay proved to be sensitive,
      detecting one genome of C. chauvoei or C. septicum per PCR and 1.79 x 10(3) C.
      chauvoei cells/g artificially contaminated muscle tissue. In tests of 11 clinical
      specimens, the real-time PCR assay yielded the same results as an established
      conventional PCR method.

PMID- 20129969
TI  - InhA1, NprA, and HlyII as candidates for markers to differentiate pathogenic from
      nonpathogenic Bacillus cereus strains.
AB  - Bacillus cereus is found in food, soil, and plants, and the ability to cause food
      borne diseases and opportunistic infection presumably varies among strains.
      Therefore, measuring harmful toxin production, in addition to the detection of
      the bacterium itself, may be key for food and hospital safety purposes. All
      previous studies have focused on the main known virulence factors, cereulide,
      Hbl, Nhe, and CytK. We examined whether other virulence factors may be specific
      to pathogenic strains. InhA1, NprA, and HlyII have been described as possibly
      contributing to B. cereus pathogenicity. We report the prevalence and expression
      profiles of these three new virulence factor genes among 57 B. cereus strains
      isolated from various sources, including isolates associated with
      gastrointestinal and nongastrointestinal diseases. Using PCR, quantitative
      reverse transcriptase PCR, and virulence in vivo assays, we unraveled these
      factors as potential markers to differentiate pathogenic from nonpathogenic
      strains. We show that the hlyII gene is carried only by strains with a pathogenic
      potential and that the expression levels of inhA1 and nprA are higher in the
      pathogenic than in the nonpathogenic group of strains studied. These data deliver
      useful information about the pathogenicity of various B. cereus strains.

PMID- 20129970
TI  - Rapid identification and differentiation of Mycobacterium avium subspecies
      paratuberculosis types by use of real-time PCR and high-resolution melt analysis
      of the MAP1506 locus.
AB  - High-resolution melt (HRM) analysis can identify sequence polymorphisms by
      comparing the melting curves of amplicons generated by real-time PCR
      amplification. We describe the application of this technique to identify
      Mycobacterium avium subspecies paratuberculosis types I, II, and III. The HRM
      approach was based on type-specific nucleotide sequences in MAP1506, a member of
      the PPE (proline-proline-glutamic acid) gene family.

PMID- 20129971
TI  - Rapid detection of Staphylococcus aureus Panton-Valentine leukocidin in clinical
      specimens by enzyme-linked immunosorbent assay and immunochromatographic tests.
AB  - Staphylococcus aureus strains producing Panton-Valentine leukocidin (PVL) have
      been epidemiologically linked to specific human infections. To evaluate
      immunological tests that may be used to diagnose infections with PVL-producing
      strains, we prospectively collected pus, respiratory tract specimens, and joint
      fluid specimens from which S. aureus had been isolated in clinical laboratories
      in six countries. An enzyme-linked immunosorbent assay (ELISA) and an
      immunochromatographic test (ICT) targeting LukS-PV were performed directly with
      clinical samples for the detection of PVL. The same tests were applied to S.
      aureus culture supernatants. The corresponding S. aureus isolates were
      characterized by PCR for the presence of the PVL locus (lukS-PV and lukF-PV) and
      the mecA gene. A total of 185 samples from 144 skin infections, 23 bone and joint
      infections, and 18 lower respiratory tract infections were analyzed. By PCR,
      72/185 S. aureus isolates were PVL locus positive (PVL(+)); 28 of these were also
      mecA positive. PVL was detected in the supernatants of all PVL(+) strains by both
      ELISA and an ICT, while no signal was observed with PVL-negative strains. The PVL
      concentrations in human clinical samples that grew PVL(+) strains ranged from 0
      to 399 microg/ml by ELISA. By the use of 0.015 microg/ml of PVL as a cutoff
      value, PVL was detected in 65/72 (90%) of the clinical samples by ELISA. The
      sensitivity and specificity of the ELISA test were 90% and 100%, respectively. By
      the ICT, PVL was detected in 57/72 (79%) of the samples, and the sensitivity and
      specificity of ICT were 79% and 100%, respectively. PVL is expressed by S. aureus
      during human infection, and a PVL-specific ELISA and ICT could be reliable tests
      for the diagnosis of infections caused by PVL-producing strains.

PMID- 20129972
TI  - Detection of Aspergillus fumigatus in a rat model of invasive pulmonary
      aspergillosis by real-time nucleic acid sequence-based amplification.
AB  - Rapid and sensitive detection of Aspergillus from clinical samples may facilitate
      the early diagnosis of invasive pulmonary aspergillosis (IPA). A real-time
      nucleic acid sequence-based amplification (NASBA) method was investigated by use
      of an inhalational rat model of IPA. Immunosuppressed male Sprague-Dawley rats
      were exposed to Aspergillus fumigatus spores for an hour in an aerosol chamber.
      Bronchoalveolar lavage (BAL) fluid, lung tissues, and whole blood were collected
      from five infected rats at 1, 24, 48, 72, and 96 h postinfection and five
      uninfected rats at the end of the experiment. Total nucleic acid (TNA) was
      extracted on an easyMAG instrument. A primer-molecular beacon set targeting 28S
      rRNA was designed to detect Aspergillus spp. The results were compared to those
      of quantitative PCR (qPCR) (18S rDNA) and quantitative culture. The analytical
      sensitivity of the real-time NASBA assay was <1 CFU/assay. A linear range of
      detection was demonstrated over 5 log units of conidia (10 to 10(5) spores). Both
      NASBA and qPCR showed a progressive increase in lung tissue burdens, while the
      CFU counts were stable over time. The fungal burdens in BAL fluid were more
      variable and not indicative of a progressive infection. The results of both real
      time assays correlated well for both sample types (r = 0.869 and P < 0.0001 for
      lung tissue, r = 0.887 and P < 0.0001 for BAL fluid). For all whole-blood
      specimens, NASBA identified Aspergillus-positive samples in the group from which
      samples were collected at 72 h postinfection (three of five samples) and the
      group from which samples were collected at 96 h postinfection (five of five
      samples), but no positive results were obtained by culture or PCR. Real-time
      NASBA is highly sensitive and useful for the detection of Aspergillus in an
      experimental model of IPA.

PMID- 20129973
TI  - The gastrointestinal tract as a nutrient-balancing organ.
AB  - Failure to provision tissues with an appropriate balance of nutrients engenders
      fitness costs. Maintaining nutrient balance can be achieved by adjusting the
      selection and consumption of foods, but this may not be possible when the
      nutritional environment is limiting. Under such circumstances, rebalancing of an
      imbalanced nutrient intake requires post-ingestive mechanisms. The first stage at
      which such post-ingestive rebalancing might occur is within the gastrointestinal
      tract (GIT), by differential release of digestive enzymes-releasing less of those
      enzymes for nutrients present in excess while maintaining or boosting levels of
      enzymes for nutrients in deficit. Here, we use an insect herbivore, the locust,
      to show for the first time that such compensatory responses occur within the GIT.
      Furthermore, we show that differential release of proteases and carbohydrases in
      response to nutritional state translate into differential extraction of
      macronutrients from host plants. The prevailing view is that physiological and
      structural plasticity in the GIT serves to maximize the rate of nutrient gain in
      relation to costs of maintaining the GIT; our findings show that GIT plasticity
      is integral to the maintenance of nutrient balance.

PMID- 20129974
TI  - The dynein-tubulin motor powers active oscillations and amplification in the
      hearing organ of the mosquito.
AB  - The design principles and specific proteins of the dynein-tubulin motor, which
      powers the flagella and cilia of eukaryotes, have been conserved throughout the
      evolution of life from algae to humans. Cilia and flagella can support both
      motile and sensory functions independently, or sometimes in parallel to each
      other. In this paper we show that this dual sensory-motile role of eukaryotic
      cilia is preserved in the most sensitive of all invertebrate hearing organs, the
      Johnston's organ of the mosquito. The Johnston's organ displays spontaneous
      oscillations, which have been identified as being a characteristic of
      amplification in the ears of mosquitoes and Drosophila. In the auditory organs of
      Drosophila and vertebrates, the molecular basis of amplification has been
      attributed to the gating and adaptation of the mechanoelectrical transducer
      channels themselves. On the basis of their temperature-dependence and sensitivity
      to colchicine, we attribute the molecular basis of spontaneous oscillations by
      the Johnston's organ of the mosquito Culex quinquefasciatus, to the dynein
      tubulin motor of the ciliated sensillae. If, as has been claimed for insect and
      vertebrate hearing organs, spontaneous oscillations epitomize amplification, then
      in the mosquito ear, this process is independent of mechanotransduction.

PMID- 20129975
TI  - Evolutionary bi-stability in pathogen transmission mode.
AB  - Many pathogens transmit to new hosts by both infection (horizontal transmission)
      and transfer to the infected host's offspring (vertical transmission). These two
      transmission modes require specific adaptations of the pathogen that can be
      mutually exclusive, resulting in a trade-off between horizontal and vertical
      transmission. We show that in mathematical models such trade-offs can lead to the
      simultaneous existence of two evolutionary stable states (evolutionary bi
      stability) of allocation of resources to the two modes of transmission. We also
      show that jumping between evolutionary stable states can be induced by gradual
      environmental changes. Using quantitative PCR-based estimates of abundance in
      seed and vegetative parts, we show that the pathogen of wheat, Phaeosphaeria
      nodorum, has jumped between two distinct states of transmission mode twice in the
      past 160 years, which, based on published evidence, we interpret as adaptation to
      environmental change. The finding of evolutionary bi-stability has implications
      for human, animal and other plant diseases. An ill-judged change in a disease
      control programme could cause the pathogen to evolve a new, and possibly more
      damaging, combination of transmission modes. Similarly, environmental changes can
      shift the balance between transmission modes, with adverse effects on human,
      animal and plant health.

PMID- 20129976
TI  - Experimental genomics of fitness in yeast.
AB  - The set of single-gene deletions in yeast can be used to evaluate the effect of
      mutation on fitness over the whole genome. The measurement of growth in pure
      culture or relative growth in mixtures has confirmed that most deletions have
      little effect in laboratory culture. Moreover, there is a sharp distinction
      between lethality and a very mild impairment of growth, with very few
      intermediate cases. Different components of fitness, such as growth rate and
      yield, are positively correlated. Growth is also positively correlated across
      environments, although new conditions of growth usually identify a few
      conditionally impaired strains. Double mutants on average show alleviating
      epistasis, although a few per cent of combinations are synthetic lethal. The
      properties of the yeast deletion set provide us with the first genome-wide
      account of fitness, although transferring these conclusions to the field is a
      task for the future.

PMID- 20129977
TI  - The quick and the dead: when reaction beats intention.
AB  - Everyday behaviour involves a trade-off between planned actions and reaction to
      environmental events. Evidence from neurophysiology, neurology and functional
      brain imaging suggests different neural bases for the control of different
      movement types. Here we develop a behavioural paradigm to test movement dynamics
      for intentional versus reaction movements and provide evidence for a 'reactive
      advantage' in movement execution, whereby the same action is executed faster in
      reaction to an opponent. We placed pairs of participants in competition with each
      other to make a series of button presses. Within-subject analysis of movement
      times revealed a 10 per cent benefit for reactive actions. This was maintained
      when opponents performed dissimilar actions, and when participants competed
      against a computer, suggesting that the effect is not related to facilitation
      produced by action observation. Rather, faster ballistic movements may be a
      general property of reactive motor control, potentially providing a useful means
      of promoting survival.

PMID- 20129978
TI  - The twilight zone: ambient light levels trigger activity in primitive ants.
AB  - Many animals become active during twilight, a narrow time window where the
      properties of the visual environment are dramatically different from both day and
      night. Despite the fact that many animals including mammals, reptiles, birds and
      insects become active in this specific temporal niche, we do not know what cues
      trigger this activity. To identify the onset of specific temporal niches, animals
      could anticipate the timing of regular events or directly measure environmental
      variables. We show that the Australian bull ant, Myrmecia pyriformis, starts
      foraging only during evening twilight throughout the year. The onset occurs
      neither at a specific temperature nor at a specific time relative to sunset, but
      at a specific ambient light intensity. Foraging onset occurs later when light
      intensities at sunset are brighter than normal or earlier when light intensities
      at sunset are darker than normal. By modifying ambient light intensity
      experimentally, we provide clear evidence that ants indeed measure light levels
      and do not rely on an internal rhythm to begin foraging. We suggest that the
      reason for restricting the foraging onset to twilight and measuring light
      intensity to trigger activity is to optimize the trade-off between predation risk
      and ease of navigation.

PMID- 20129979
TI  - The impact of clonal mixing on the evolution of social behaviour in aphids.
AB  - Reports of substantial clonal mixing measured in social aphid colonies seem, on
      the face of it, to rule out population structure as an explanation of this
      enigmatic insect's social behaviour. To clarify how selection operates in aphids,
      and to disentangle direct and indirect fitness components, we present a model of
      the life cycle of a typical colony-dwelling aphid. The model incorporates
      ecological factors and includes a trade-off between investing in social behaviour
      and investing in reproduction. Our focus on inclusive fitness contrasts with
      previous approaches that optimize colony output. Through deriving a variant of
      Hamilton's rule, we show that a simple relationship can be established between
      the patch-carrying capacity and immigration rates into patches. Our results
      indicate that the levels of clonal mixing reported are not inconsistent with
      social behaviour. We discuss our model in terms of the evolutionary origins of
      social behaviour in aphids.

PMID- 20129980
TI  - Spawning salmon and the phenology of emergence in stream insects.
AB  - Phenological dynamics are controlled by environmental factors, disturbance
      regimes and species interactions that alter growth or mortality risk. Ecosystem
      engineers can be a key source of disturbance, yet their effects on the
      phenologies of co-occurring organisms are virtually unexplored. We investigated
      how the abundance of a dominant ecosystem engineer, spawning sockeye salmon
      (Oncorhynchus nerka), alters the emergence phenology of stream insects. In
      streams with high densities of salmon, peak insect emergence occurred in early
      July, immediately prior to salmon spawning. By contrast, peak insect emergence in
      streams with low densities of salmon was weeks later and more protracted. The
      emergence of specific taxa was also significantly related to salmon density. A
      common rearing experiment revealed that differences in emergence timing are
      maintained in the absence of spawning salmon. We hypothesize that these patterns
      are probably driven by predictable and severe disturbance from nest-digging
      salmon driving local adaptation and being a trait filter of insect emergence.
      Thus, salmon regulate the timing and duration of aquatic insect emergence, a
      cross-ecosystem flux from streams to riparian systems.

PMID- 20129981
TI  - Long-term evolution of antigen repertoires among carried meningococci.
AB  - Most studies of bacterial pathogen populations have been based on isolates
      collected from individuals with disease, or their contacts, over short time
      periods. For commensal organisms that occasionally cause disease, such as
      Neisseria meningitidis, however, the analysis of isolates from long-term
      asymptomatic carriage is necessary to elucidate their evolution and population
      structure. Here, we use mathematical models to analyse the structuring and
      dynamics of three vaccine-candidate antigens among carried meningococcal isolates
      collected over nearly 30 years in the Czech Republic. The data indicate that
      stable combinations of antigenic alleles were maintained over this time period
      despite evidence for high rates of recombination, consistent with theoretical
      models in which strong immune selection can maintain non-overlapping combinations
      of antigenic determinants in the presence of recombination. We contrast this
      antigenic structure with the overlapping but relatively stable combinations of
      the housekeeping genes observed among the same isolates, and use a novel network
      approach to visualize these relationships.

PMID- 20129982
TI  - An unexpected advantage of whiteness in horses: the most horsefly-proof horse has
      a depolarizing white coat.
AB  - White horses frequently suffer from malign skin cancer and visual deficiencies
      owing to their high sensitivity to the ultraviolet solar radiation. Furthermore,
      in the wild, white horses suffer a larger predation risk than dark individuals
      because they can more easily be detected. In spite of their greater
      vulnerability, white horses have been highly appreciated for centuries owing to
      their natural rarity. Here, we show that blood-sucking tabanid flies, known to
      transmit disease agents to mammals, are less attracted to white than dark horses.
      We also demonstrate that tabanids use reflected polarized light from the coat as
      a signal to find a host. The attraction of tabanids to mainly black and brown fur
      coats is explained by positive polarotaxis. As the host's colour determines its
      attractiveness to tabanids, this parameter has a strong influence on the parasite
      load of the host. Although we have studied only the tabanid-horse interaction,
      our results can probably be extrapolated to other host animals of polarotactic
      tabanids, as the reflection-polarization characteristics of the host's body
      surface are physically the same, and thus not species-dependent.

PMID- 20129983
TI  - Many hexapod groups originated earlier and withstood extinction events better
      than previously realized: inferences from supertrees.
AB  - Comprising over half of all described species, the hexapods are central to
      understanding the evolution of global biodiversity. Direct fossil evidence
      suggests that new hexapod orders continued to originate from the Jurassic
      onwards, and diversity is presently higher than ever. Previous studies also
      suggest that several shifts in net diversification rate have occurred at higher
      taxonomic levels. However, their inferred timing is phylogeny dependent. We re
      examine these issues using the supertree approach to provide, to our knowledge,
      the first composite estimates of hexapod order-level phylogeny. The Purvis matrix
      representation with parsimony method provides the most optimal supertree, but
      alternative methods are considered. Inferring ghost ranges shows richness of
      terminal lineages in the order-level phylogeny to peak just before the end
      Permian extinction, rather than the present day, indicating that at least 11 more
      lineages survived this extinction than implied by fossils alone. The major
      upshift in diversification is associated with the origin of wings/wing folding
      and for the first time, to our knowledge, significant downshifts are shown
      associated with the origin of species-poor taxa (e.g. Neuropterida, Zoraptera).
      Polyneopteran phylogeny, especially the position of Zoraptera, remains important
      resolve because this influences findings regarding shifts in diversification. Our
      study shows how combining fossil with phylogenetic information can improve
      macroevolutionary inferences.

PMID- 20129984
TI  - Morphological plasticity reduces the effect of poor developmental conditions on
      fledging age in mourning doves.
AB  - Developmental plasticity can be integral in adapting organisms to the environment
      experienced during growth. Adaptive plastic responses may be especially important
      in prioritizing development in response to stress during ontogeny. To evaluate
      this, I examined how developmental conditions for mourning doves related to early
      growth and how this affected fledging age, an important life-history transition
      for birds. The life history of mourning doves is consistent with strong selective
      pressure to minimize fledging age. Therefore, I predicted that in the face of
      nutritional stress associated with experimental brood-size increases, young would
      prioritize growth to structures that promote early fledging to reduce the effect
      of slowed overall growth on fledging age. Increasing brood size slowed overall
      structural growth of nestlings and affected the relative allocation of growth
      among different body parts. Total wing area was the best predictor of fledging
      age and individuals from larger broods had larger wings relative to overall body
      size. Although nestlings from larger broods fledged at later ages owing to slower
      overall growth, prioritization of wing growth reduced this effect by an estimated
      1.6 days relative to the delay if plasticity among body parts had not occurred.
      This was an 11 per cent reduction in the predicted developmental time it took to
      reach this important life-history transition. Results demonstrate that
      preferential allocation to wing growth can affect the timing of this life-history
      transition and that morphological plasticity during development can have adaptive
      near-term effects during avian development.

PMID- 20129985
TI  - Behavioural display systems across nine Anolis lizard species: sexual dimorphisms
      in structure and function.
AB  - Relationships between structure and function are a primary focus in biology, yet
      they are most often considered within individual species. Sexually dimorphic
      communication behaviours and the morphology of associated structures can vary
      widely, even among closely related species, and these traits provide an ideal
      opportunity to investigate the evolution of structure-function patterns. Using
      nine Anolis lizard species, we addressed a series of questions regarding sex
      differences in and the evolution of relationships between extension of the throat
      fan (dewlap) and morphology of the muscles and cartilage controlling it. The main
      results indicated that within species, males displayed the dewlap more often than
      females and consistently exhibited larger associated structures. These data are
      consistent with work in other vertebrates in which corresponding sex differences
      in reproductive morphology and behaviour have been documented. Across species,
      however, we found no evidence that the rate of dewlap extension evolved in
      association with dewlap morphology. Thus, we provide an example of traits that,
      when considered in a phylogenetic framework, exhibited limited associations
      between behaviour and morphology, perhaps as the result of constraints imposed by
      the ecological contexts in which different species occur.

PMID- 20129986
TI  - Dispersal and ejaculatory strategies associated with exaggeration of weapon in an
      armed beetle.
AB  - Weapons used in male fighting can be costly to males and are often reported to
      trade off with other characters such as wings or spermatogenic investment. This
      study investigated whether increased investment into weapons can generate
      evolutionary changes in mating strategy for armed males. Male flour beetles,
      Gnatocerus cornutus, have enlarged mandibles that are used in male-male
      competition. We subjected these weapons to 12 generations of bidirectional
      selection and found trade-offs between weapons and two other male characters:
      wing and testis size. In addition, probably as a consequence of the observed
      changes in investment, dispersal ability and ejaculatory volume differ
      significantly between the lines. This indicates that the exaggeration of a weapon
      can be associated with dispersal and ejaculatory strategies. Thus, altered
      investment into weapons can lead to correlated changes in life-history traits.

PMID- 20129987
TI  - Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that
      regulates the circulating levels of vital glucocorticoid hormones. The activity
      of the HPA axis is characterized not only by a classic circadian rhythm, but also
      by an ultradian pattern of discrete pulsatile release of glucocorticoids. A
      number of psychiatric and metabolic diseases are associated with changes in
      glucocorticoid pulsatility, and it is now clear that glucocorticoid responsive
      genes respond to these rapid fluctuations in a biologically meaningful way.
      Theoretical modelling has enabled us to identify and explore potential mechanisms
      underlying the ultradian activity in this axis, which to date have not been
      identified successfully. We demonstrate that the combination of delay with feed
      forward and feedback loops in the pituitary-adrenal system is sufficient to give
      rise to ultradian pulsatility in the absence of an ultradian source from a supra
      pituitary site. Moreover, our model enables us to predict the different patterns
      of glucocorticoid release mediated by changes in hypophysial-portal
      corticotrophin-releasing hormone levels, with results that parallel our
      experimental in vivo data.

PMID- 20129988
TI  - An experimental test of a fundamental food web motif.
AB  - Large-scale changes to the world's ecosystem are resulting in the deterioration
      of biostructure-the complex web of species interactions that make up ecological
      communities. A difficult, yet crucial task is to identify food web structures, or
      food web motifs, that are the building blocks of this baroque network of
      interactions. Once identified, these food web motifs can then be examined through
      experiments and theory to provide mechanistic explanations for how structure
      governs ecosystem stability. Here, we synthesize recent ecological research to
      show that generalist consumers coupling resources with different interaction
      strengths, is one such motif. This motif amazingly occurs across an enormous
      range of spatial scales, and so acts to distribute coupled weak and strong
      interactions throughout food webs. We then perform an experiment that illustrates
      the importance of this motif to ecological stability. We find that weak
      interactions coupled to strong interactions by generalist consumers dampen strong
      interaction strengths and increase community stability. This study takes a
      critical step by isolating a common food web motif and through clear,
      experimental manipulation, identifies the fundamental stabilizing consequences of
      this structure for ecological communities.

PMID- 20129989
TI  - Birds learn to use distastefulness as a signal of toxicity.
AB  - Aposematic prey advertise their toxicity using conspicuous visual signals that
      predators quickly learn to avoid. However, it is advantageous for predators not
      to simply avoid toxic prey, but to learn about the amount of toxin that prey
      contain, and include them in their diets when the nutritional gains are high
      relative to the costs of ingesting the toxin. Therefore, when foraging on a
      defended prey population where individuals vary in their toxin concentration,
      predators should learn to use cues which distinguish prey with different levels
      of toxicity in order to include less defended individuals in their diets. In this
      experiment, we found that European starlings (Sturnus vulgaris) could learn to
      use a bitter taste to predict the amount of toxin that individual prey contained,
      and use that information to preferentially ingest less toxic prey to maximize
      their nutrient intake relative to the amount of toxin ingested. Our results
      suggest that bitter tastes could evolve as reliable signals of toxicity, and can
      help to explain why many toxins taste bitter. They also highlight the need to
      develop new mathematical simulations of the evolution of prey defences which
      incorporate the adaptive decision-making processes underlying nutrient and toxin
      management.

PMID- 20129990
TI  - Mate choice and mate competition by a tropical hummingbird at a floral resource.
AB  - The influence of male territorial and foraging behaviours on female choice has
      received little attention in studies of resource-defence mating systems even
      though such male behaviours are thought to affect variation in their territory
      quality and mating success. Here we show that female purple-throated carib
      hummingbirds Eulampis jugularis preferred to mate with males that had high
      standing crops of nectar on their flower territories. A male's ability to
      maintain high nectar standing crops on his territory not only depended on the
      number of flowers in his territory, but also on his ability to enhance his
      territory through the prevention of nectar losses to intruders. We observed that
      males defended nectar supplies that were two to five times greater than their
      daily energy needs and consistently partitioned their territories in order to
      provide some resources to attract intruding females as potential mates. Such
      territorial behaviour resulted in males defending some flowers for their own food
      and other flowers as food for intruding females. Collectively, our results
      suggest that variation in mating success among males is driven primarily by
      variation in territory quality, which ultimately depends on a male's fighting
      ability and size.

PMID- 20129991
TI  - Reproductive constraints, direct fitness and indirect fitness benefits explain
      helping behaviour in the primitively eusocial wasp, Polistes canadensis.
AB  - A key step in the evolution of sociality is the abandonment of independent
      breeding in favour of helping. In cooperatively breeding vertebrates and
      primitively eusocial insects, helpers are capable of leaving the group and
      reproducing independently, and yet many do not. A fundamental question therefore
      is why do helpers help? Helping behaviour may be explained by constraints on
      independent reproduction and/or benefits to individuals from helping. Here, we
      examine simultaneously the reproductive constraints and fitness benefits
      underlying helping behaviour in a primitively eusocial paper wasp. We gave 31
      helpers the opportunity to become egg-layers on their natal nests by removing
      nestmates. This allowed us to determine whether helpers are reproductively
      constrained in any way. We found that age strongly influenced whether an ex
      helper could become an egg-layer, such that young ex-helpers could become egg
      layers while old ex-helpers were less able. These differential reproductive
      constraints enabled us to make predictions about the behaviours of ex-helpers,
      depending on the relative importance of direct and indirect fitness benefits. We
      found little evidence that indirect fitness benefits explain helping behaviour,
      as 71 per cent of ex-helpers left their nests before the end of the experiment.
      In the absence of reproductive constraints, however, young helpers value direct
      fitness opportunities over indirect fitness. We conclude that a combination of
      reproductive constraints and potential for future direct reproduction explain
      helping behaviour in this species. Testing several competing explanations for
      helping behaviour simultaneously promises to advance our understanding of social
      behaviour in animal groups.

PMID- 20129992
TI  - Disclosure of donor conception in single-mother families: views and concerns.
AB  - BACKGROUND: Despite the prevalence of donor conception and the worldwide trend
      towards openness, there has been little research on whether parents do disclose
      the nature of the conception to their donor-conceived children. This analysis
      focuses on whether and how older Israeli single mothers disclose to their
      children that were conceived using a donor and whether the donor conception
      causes concern for them. METHODS: Sixty-two single mothers of donor-conceived
      children in Israel were asked whether they would like to know the identity of the
      sperm donor; whether they would like their children to know the identity of the
      sperm donor when reaching the age of 18, whether they disclosed the circumstances
      of conception to their children or intend to do so in the future; and whether the
      sperm donation causes concern to them. RESULTS: The mothers were divided on
      whether they wanted to know the identity of the sperm donor. However, less than
      one-fifth of them did not want their children to have identifying information
      about the genetic father at the age of 18. About two-thirds of the mothers had
      not yet disclosed the donor conception to their children but intended to do so in
      the future. A total of 77.4% of the mothers reported being concerned about the
      donor conception: for the psychosocial development of the child, fear of genetic
      disorders, fear of incest and lack of certainty of access to genetic information
      when needed. CONCLUSIONS: The tendency to postpone the disclosure reveals the
      difficulty of these mothers in finding the appropriate way of sharing the
      information about the conception with their children. Given the importance
      attached to the age of disclosure and the mothers' concern for the psychosocial
      development of their children, more professional counselling in this area is
      warranted.

PMID- 20129993
TI  - Surgery for bladder endometriosis: long-term results and concomitant management
      of associated posterior deep lesions.
AB  - BACKGROUND: Deep infiltrating endometriosis (DIE) is presented as a disease with
      high recurrence risk. Bladder DIE is the most frequent location in cases of
      urinary endometriosis. Surgical removal has been recommended for bladder DIE but
      long-term outcomes remains unevaluated. The objectives of this study are to
      evaluate the rate of recurrence after partial cystectomy for patients presenting
      with bladder DIE and to outline the surgical modalities for handling associated
      posterior DIE nodules. METHODS: Seventy-five consecutive patients with
      histologically proved bladder DIE were enrolled at a single tertiary academic
      center between June 1992 and December 2007. A partial cystectomy was performed
      for each patient. Complete surgical exeresis of all associated symptomatic DIE
      lesions was carried out during the same surgical procedure. Bladder DIE patients
      were classified into three groups: patients with isolated bladder DIE (Group A);
      patients with associated symptomatic posterior DIE (Group B); patients with
      associated asymptomatic posterior DIE (Group C). Bladder DIE recurrence was
      defined as a clinical reappearance of the disease or radiological evidence that
      mandated a new surgical procedure. We assessed pelvic pain symptoms pre- and post
      operatively using a 10-cm visual analogue scale. RESULTS: In a series of 627
      patients with DIE, we observed 75 patients (12%) with bladder DIE. With a 50.9 +/
      44.6 months mean follow-up after partial cystectomy no patient presented
      evidence of bladder DIE recurrence. Post-operatively, we observed a significant
      improvement with respect to pain symptoms, with only two patients (2.7%)
      developing major complications during follow-up. Among patients with non-operated
      associated asymptomatic posterior DIE lesions (n = 15), a second surgical
      procedure indicated for pain symptoms was necessary in only one patient (6.7%).
      CONCLUSIONS: For patients presenting with bladder DIE, no patients required
      further surgery for bladder recurrence after radical surgery consisting in
      partial cystectomy. Exeresis of associated posterior DIE nodules is indicated
      only when they are symptomatic.

PMID- 20129994
TI  - Should access to fertility treatment be determined by female body mass index?
AB  - Resource allocation towards fertility treatment has been extensively debated in
      countries where fertility treatment is publicly-funded. Medical, social and
      ethical aspects have been evaluated prior to allocation of resources. Analysis of
      cost-effectiveness, risks and benefits and poor success rates have led to calls
      of restricting fertility treatment to obese women. In this debate article, we
      critically appraise the evidence underlying this issue and highlight the problems
      with such a policy. Poor success rate of treatment is unsubstantiated as there is
      insufficient evidence to link high body mass index (BMI) to reduction in live
      birth. Obstetric complications have a linear relationship with BMI but are
      significantly influenced by maternal age. The same is true for miscarriage rates
      which are influenced by the confounding factors of polycystic ovary syndrome and
      age. Studies have shown that the direct costs per live birth are no greater for
      overweight and obese women. With changing demographics over half the reproductive
      age population is overweight or obese. Restricting fertility treatment on the
      grounds of BMI would cause stigmatization and lead to inequity, feelings of
      injustice and social tension as affluent women manage to bypass these draconian
      restrictions. Time lost and poor success of conventional weight loss strategies
      would jeopardize the chances of conception for many women.

PMID- 20129995
TI  - Seen but not heard? Children in clinical trials.

PMID- 20129996
TI  - Clinical implication of 18F-fluorodeoxyglucose PET/CT in monitoring disease
      activity in spondyloarthritis.

PMID- 20129997
TI  - Use of 99mTc-anti-CD3 scintigraphy in the differential diagnosis of rheumatic
      diseases.
AB  - OBJECTIVES: The aim of this study was to assess the use of anti-CD3, labelled
      with technetium-99m scintigraphy, for evaluating the joints of patients with RA,
      juvenile idiopathic arthritis (JIA), OA and gouty arthritis, and to establish the
      diagnosis parameters for each disease. METHODS: We evaluated 2044 joints from 77
      patients with rheumatic diseases. The clinical evaluation consisted of laboratory
      assays; examination for joint inflammation (pain and/or oedema); and for patients
      with RA, the disease activity score of 28 joints. To evaluate the sensitivity and
      specificity of 99mTc-anti-CD3 in detecting disease activity, patients received an
      injection of the radiopharmaceutical compound 99mTc-anti-CD3, and underwent a
      scintigraphy scan 1 h later. Scanning was repeated 3 h later. As a control, after
      2 days, the patient was injected with 99mTc-non-specific human immunoglobulins,
      and scintigraphy scanning performed at 1 and 3 h after the injection. The
      intensity of uptake and the pattern of activity were defined, and Spearman's
      correlation and analysis of variance used for statistical evaluation. RESULTS:
      Diagnosis criteria were established for 99mTc-anti-CD3 uptake in different
      diseases. RA and JIA showed joint uptake with progressive increase in late
      images. Gouty arthritis showed joint uptake with decrease during the late images.
      Joint uptake was low or absent in patients with OA, although when present the
      joint uptake decreased during the examination. CONCLUSION: 99mTc-anti-CD3
      scintigraphy is a useful method in the differential diagnosis of rheumatic
      diseases.

PMID- 20129998
TI  - D-dimer level as a risk factor for postoperative venous thromboembolism in
      Japanese women with gynecologic cancer.
AB  - BACKGROUND: The purpose of the present study was to evaluate whether early
      postoperative D-dimer levels and certain pre-, intra-, and postoperative
      parameters can be used to predict venous thromboembolism (VTE) in gynecologic
      cancer patients. MATERIALS AND METHODS: We prospectively evaluated 267
      gynecologic cancer patients who underwent surgery at our institution. The plasma
      D-dimer level was measured serially before the operation and on certain
      postoperative days. After the operation, primary screening for VTE was undertaken
      by meticulous examination for clinical signs and elevation of the plasma D-dimer
      level. Seventy-five patients underwent multidetector row computed tomography and
      were subjected to further investigations. RESULTS: VTE was detected in 21 of the
      75 patients. There were significant differences in the D-dimer value between VTE
      positive and VTE-negative patients on postoperative days 3, 5, and 7. The optimal
      cut-off value for the postoperative D-dimer level was determined as 5 mug/ml on
      day 3. Logistic regression multivariate analysis revealed that high D-dimer
      values on postoperative day 3, the use of recombinant human erythropoietin
      (rHuEPO), and non-O blood group were independent risk factors for postoperative
      VTE. CONCLUSION: High plasma D-dimer level on postoperative day 3, the use of
      rHuEPO, and non-O blood group were independent risk factors for postoperative
      VTE.

PMID- 20130000
TI  - Americans are less healthy than 10 years ago, shows national survey.

PMID- 20130002
TI  - "Disappointing" progress in children's health despite pound10bn funding.

PMID- 20130003
TI  - Stroke strategy in England is improving acute care, shows audit.

PMID- 20130004
TI  - Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal
      hyperexcitability.
AB  - LGI1 in humans is responsible for a predisposition to autosomal dominant partial
      epilepsy with auditory features (ADPEAF). However, mechanisms of how LGI1
      mutations cause epilepsy remain unclear. We have used a mouse chromosome
      engineering strategy to create a null mutation for the gene ortholog encoding
      LGI1. The Lgi1 null mutant mice show no gross overall developmental abnormalities
      from routine histopathological analysis. After 12-18 days of age, the homozygous
      mutant mice all exhibit myoclonic seizures accompanied by rapid jumping and
      running and die shortly thereafter. The heterozygous mutant mice do not develop
      seizures. Electrophysiological analysis demonstrates an enhanced excitatory
      synaptic transmission by increasing the release of the excitatory
      neurotransmitter glutamate, suggesting a basis for the seizure phenotype. This
      mouse model, therefore, provides novel insights into the mechanism behind ADPEAF
      and offers a new opportunity to study the mechanism behind the role of LGI1 in
      susceptibility to myoclonic seizures.

PMID- 20130005
TI  - A toddler with pallor and recurrent infection.

PMID- 20130006
TI  - Gradually worsening shortness of breath.

PMID- 20130011
TI  - Scientists protest about Quebec's "hypocrisy" over export of asbestos.

PMID- 20130012
TI  - Bad medicine: osteoporosis.

PMID- 20130013
TI  - Coexpression analysis of tomato genes and experimental verification of
      coordinated expression of genes found in a functionally enriched coexpression
      module.
AB  - Gene-to-gene coexpression analysis is a powerful approach to infer the function
      of uncharacterized genes. Here, we report comprehensive identification of
      coexpression gene modules of tomato (Solanum lycopersicum) and experimental
      verification of coordinated expression of module member genes. On the basis of
      the gene-to-gene correlation coefficient calculated from 67 microarray
      hybridization data points, we performed a network-based analysis. This
      facilitated the identification of 199 coexpression modules. A gene ontology
      annotation search revealed that 75 out of the 199 modules are enriched with genes
      associated with common functional categories. To verify the coexpression
      relationships between module member genes, we focused on one module enriched with
      genes associated with the flavonoid biosynthetic pathway. A non-enzyme, non
      transcription factor gene encoding a zinc finger protein in this module was
      overexpressed in S. lycopersicum cultivar Micro-Tom, and expression levels of
      flavonoid pathway genes were investigated. Flavonoid pathway genes included in
      the module were up-regulated in the plant overexpressing the zinc finger gene.
      This result demonstrates that coexpression modules, at least the ones identified
      in this study, represent actual transcriptional coordination between genes, and
      can facilitate the inference of tomato gene function.

PMID- 20130014
TI  - Towards a new order in cardiovascular medicine: re-engineering through global
      collaboration.

PMID- 20130015
TI  - Variability in the prioritization of patients for cataract extraction.
AB  - OBJECTIVE: The aim of this study was to compare time spent waiting for cataract
      extraction across various hospitals and to determine if it was influenced by
      severity of disease or patient characteristics. DESIGN: Ambispective cohort
      study. Clinical, sociodemographic, and health-related quality of life data were
      collected along with time spent on the waiting list. SETTING: Twelve hospitals in
      four regions of Spain. PARTICIPANTS: A total of 4043 patients who were waiting
      for being intervened on cataracts in the participant centres were recruited
      prospectively. Exposition variables Priority was assigned retrospectively using a
      previously validated scoring system. MAIN OUTCOME MEASURE: Time spent on waiting
      list. RESULTS: Statistically significant differences in time spent on the waiting
      list (P < 0.0001) were observed across the hospitals, even after adjusting for
      pathology, age, social dependency, laterality of the cataract and number of
      inappropriate interventions in each centre. Waiting time was not correlated with
      preintervention visual acuity, preintervention visual function measured by the VF
      14 or priority score. CONCLUSIONS: Allocation of cataract surgery does not appear
      to be correlated with the need for surgery or the likely benefit to be derived
      from it in the Spanish participant centres. The use of explicit and standardized
      priority criteria could provide a fairer, more rational way to manage waiting
      lists for this procedure and may help to reduce unnecessary variation on access
      to health care.

PMID- 20130016
TI  - This paper was published in error and has been removed.

PMID- 20130017
TI  - Hearing experience and receptive vocabulary development in deaf children with
      cochlear implants.
AB  - This study investigated receptive vocabulary delay in deaf children with cochlear
      implants. Participants were 23 children with profound hearing loss, ages 6-14
      years, who received a cochlear implant between ages 1.4 and 6 years. Duration of
      cochlear implant use ranged from 3.7 to 11.8 years. Peabody Picture Vocabulary
      Test, Third Edition (PPVT-III) data were analyzed first by examining children's
      errors for evidence of difficulty in specific lexical content areas, and second
      by calculating standard scores with reference to hearing age (HA) (i.e.,
      chronological age [CA]--age at implantation) rather than CA. Participants showed
      evidence of vocabulary understanding across all PPVT-III content categories with
      no strong evidence of disproportionate numbers of errors in any specific content
      area despite below-average mean standard scores. However, whereas mean standard
      scores were below the test mean established for hearing children when based on
      CA, they were within the average range for hearing children when calculated based
      on HA. Thus, children's vocabulary knowledge was commensurate with years of
      cochlear implant experience, providing support for the role of spoken language
      experience in vocabulary acquisition.

PMID- 20130018
TI  - The integrated stress response-associated signals modulates intestinal tumor cell
      growth by NSAID-activated gene 1 (NAG-1/MIC-1/PTGF-beta).
AB  - Phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2alpha)
      is a critical convergence point of the integrated stress response (ISR), which
      supports eukaryotic cellular adaptation to diverse stressful conditions,
      including the endoplasmic reticulum (ER) stress by global protein translational
      arrest and induction of numerous stress-triggered cytoprotective genes. Challenge
      with non-steroidal anti-inflammatory drug (NSAID) leads to ER perturbation that
      may sensitize cancer cells to drug-induced apoptosis. Here, we examined the ER
      stress signals in the context of NSAID exposure and the induction of the critical
      tumor suppressor, NSAID-activated gene 1 (NAG-1), in the epithelial cancer cells.
      Sulindac sulfide, the active sulindac metabolite, was shown to trigger the ISRs
      via eIF2alpha kinase such as RNA-dependent protein kinase-related endoplasmic
      reticulum kinase (PERK) and RNA-dependent protein kinase (PKR). ER stress markers
      such as glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and
      activating transcription factor (ATF)-3 were enhanced by sulindac sulfide in
      colon cancer cells. In these cells, the PERK-activated ATF3-CHOP signaling
      pathway mediated the gene expression of pro-apoptotic NAG-1- and NSAID-induced
      apoptosis. In contrast, PKR protein was not involved in the signaling cascade for
      the gene expression of CHOP-linked NAG-1. Instead, PKR mediated activation of pro
      survival extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway,
      which was enhanced by NAG-1 suppression in response to cytotoxic sulindac sulfide
      exposure. PKR-ERK1/2 activation may thus contribute to the defensive cellular
      response to cytotoxic NSAIDs while drug-mediated ER stress triggers the pro
      apoptotic NAG-1 production in human colon cancer cells.

PMID- 20130019
TI  - The role of RPA2 phosphorylation in homologous recombination in response to
      replication arrest.
AB  - Failure to reactivate stalled or collapsed DNA replication forks is a potential
      source of genomic instability. Homologous recombination (HR) is a major mechanism
      for repairing the DNA damage resulting from replication arrest. The single-strand
      DNA (ssDNA)-binding protein, replication protein A (RPA), plays a major role in
      multiple processes of DNA metabolism. However, the role of RPA2
      hyperphosphorylation, which occurs in response to DNA damage, had been unclear.
      Here, we show that hyperphosphorylated RPA2 associates with ssDNA and recombinase
      protein Rad51 in response to replication arrest by hydroxyurea (HU) treatment. In
      addition, RPA2 hyperphosphorylation is critical for Rad51 recruitment and HR
      mediated repair following HU. However, RPA2 hyperphosphorylation is not essential
      for both ionizing radiation (IR)-induced Rad51 foci formation and I-Sce-I
      endonuclease-stimulated HR. Moreover, we show that expression of a
      phosphorylation-deficient mutant of RPA2 leads to increased chromosomal
      aberrations following HU treatment but not after exposure to IR. Finally, we
      demonstrate that loss of RPA2 hyperphosphorylation results in a loss of viability
      when cells are confronted with replication stress whereas cells expressing
      hyperphosphorylation-defective RPA2 or wild-type RPA2 have a similar sensitivity
      to IR. Thus, our data suggest that RPA2 hyperphosphorylation plays a critical
      role in maintenance of genomic stability and cell survival after a DNA
      replication block via promotion of HR.

PMID- 20130020
TI  - Bystander effects induced by chemicals and ionizing radiation: evaluation of
      changes in gene expression of downstream MAPK targets.
AB  - Radiation-induced bystander effects have been evaluated extensively, including
      the involvement of the mitogen-activated protein kinase (MAPK) pathways. However,
      few studies have examined the ability of chemicals to induce bystander effects,
      and the molecular mechanisms involved in chemical bystander effects have not been
      investigated. We have previously demonstrated the ability of mitomycin C (MMC)
      and phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid
      cells. Here, we demonstrate changes in the expression of MAPK target genes
      following bystander exposure to MMC or PHL or ionizing radiation. The expression
      changes of 18 genes, which code for proteins that are downstream targets of MAPK
      proteins, were evaluated at various time points following direct or bystander
      exposure to MMC, PHL and ionizing radiation. The 18 genes were analysed as groups
      belonging to one of the seven possible combinations of the three MAPK pathways.
      We observed statistically significant changes in expression of several genes
      following exposure to each agent. However, when the expression changes were
      analysed in the bystander cells alone, significant increases in expression of
      MAPK target genes were observed for MMC- and radiation-induced bystander effects
      but not for PHL. PHL is an acknowledged radiomimetic agent; however, in the
      present study, PHL responses did not resemble those of radiation. These results
      provide evidence for bystander-induced changes in MAPK proteins and downstream
      targets and suggest that the bystander effects are a part of a general stress
      response.

PMID- 20130021
TI  - Predose blood gene expression profiles might identify the individuals susceptible
      to carbon tetrachloride-induced hepatotoxicity.
AB  - Although the extent of chemical-induced liver injury differs substantially from
      individual to individual, it is very hard to identify susceptible population
      priori to chemical exposure. We report here that the gene expression of the blood
      samples collected predose might identify the susceptible population without
      actual exposure to hepatotoxicant. The innate gene expressions in the blood
      samples collected at predose were compared using whole-genome microarray analysis
      and semiquantitative PCR with the extent of hepatotoxicity following the
      treatment of a model hepatotoxicant, carbon tetrachloride (CCl(4)) posteriori.
      The expression of 18 genes was found to innately differ in the blood of the
      susceptible animals from the resistant to CCl(4)-induced hepatotoxicity. Of these
      18 genes, three genes, NADH dehydrogenase subunit 6 (ND6), transient receptor
      potential cation channel, subfamily C, member 6 (Trpc6), and tetraspanin 12
      (Tspan12), were found to be different reproducibly in real-time PCR analysis with
      independent sets of animals. Of particular note, animals with the low expression
      level of ND6 and Tspan12 showed significantly higher susceptibility to CCl(4)
      induced hepatotoxicity indeed. This study demonstrated that blood gene expression
      profiling might identify the susceptible individuals to chemical-induced
      hepatotoxicity without actual chemical exposure, providing a novel and important
      methodology for the prevention of drug-induced hepatotoxicity.

PMID- 20130022
TI  - Dioxin exposure disrupts the differentiation of mouse embryonic stem cells into
      cardiomyocytes.
AB  - Experimental exposure of fish, birds, and rodents to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD; dioxin) causes multiple Ah receptor-mediated developmental
      abnormalities, an observation consistent with compelling evidence in human
      populations that TCDD exposure is responsible for a significant incidence of
      birth defects. To characterize molecular mechanisms that might explain the
      developmental effects of dioxin, we have studied the consequences of TCDD
      exposure on the differentiation of mouse embryonic stem (ES) cells in culture and
      on the expression of genes, including those coding for homeodomain containing
      transcription factors, with a role in progression of tissue differentiation and
      embryonic identity during development. We find that TCDD treatment causes
      expression changes in a number of homeobox genes concomitant with Ah receptor
      recruitment to the promoters of many of these genes, whether under naive or
      dioxin-activated conditions. TCDD exposure also derails temporal expression
      trajectories of developmentally regulated genes in a wide diversity of
      differentiation pathways, including genes with functions in neural and
      cardiovascular development, self-renewal, hematopoiesis and mesenchymal lineage
      specification, and Notch and Wnt pathways. Among these, we find that TCDD
      represses the expression of the cardiac development-specific Nkx2.5 homeobox
      transcription factor, of cardiac troponin-T and of alpha- and beta-myosin heavy
      chains, inhibiting the formation of beating cardiomyocytes, a characteristic
      phenotype of differentiating mouse ES cells in culture. These data identify
      potential pathways for dioxin to act as a developmental teratogen, possibly
      critical to cardiovascular development and disease, and provide molecular targets
      that may help us understand the molecular basis of Ah receptor-mediated
      developmental toxicity.

PMID- 20130023
TI  - Semi-selective broth improves screening for methicillin-resistant Staphylococcus
      aureus.
AB  - OBJECTIVES: To evaluate two enrichment broths for methicillin-resistant
      Staphylococcus aureus (MRSA) detection and compare results with direct plating.
      METHODS: Swabs from 1224 patients were re-analysed for MRSA in a central
      laboratory (Munster) using six methods. Swabs were suspended in 0.5 mL of non
      selective enrichment broth (NB) and vortexed. Aliquots of 100 microL were
      inoculated on/into: (I) ChromID MRSA agar; (II) Columbia sheep blood (5%) agar
      (BA) and ChromID MRSA; (III, IV) NB incubated overnight followed by plating on BA
      and ChromID MRSA; and (V, VI) a semi-selective broth containing cefoxitin and
      aztreonam (TSB-SSI) incubated overnight followed by plating on BA and ChromID
      MRSA. In III-VI, 100 microL of the enriched broth was plated on each agar.
      RESULTS: The combined MRSA-positive rate was 21.5%. MRSA isolates detected by
      each method were: TSB-SSI, n = 223; NB, n = 205; BA and ChromID MRSA, n = 203;
      ChromID MRSA alone, n = 183. TSB-SSI detected more positive throat samples than
      the comparators and significantly reduced methicillin-susceptible S. aureus
      (MSSA) growth. The maximum sensitivity obtained was only 85%, possibly due to the
      study design using pre-used swabs and dilution of swab material. For 997 samples,
      results from Munster were compared with initial results. Peripheral laboratories
      identified 172 MRSA compared with Munster where 186, 186 and 204 MRSA were found
      for direct plating, NB and TSB-SSI broth, respectively. CONCLUSIONS: TSB-SSI was
      superior to both NB and direct plating on ChromID MRSA and BA. Despite re-using
      swabs for the study, we showed that routine diagnostic screening could be
      significantly improved, using a semi-selective enrichment broth.

PMID- 20130024
TI  - Fungicidal activity of miconazole against Candida spp. biofilms.
AB  - OBJECTIVES: Although azole antifungals are considered to be fungistatic,
      miconazole has fungicidal activity against planktonic Candida albicans cells,
      presumably associated with the induction of reactive oxygen species (ROS)
      production. Only few data are available concerning the effect of miconazole
      against sessile C. albicans cells. In the present study, the fungicidal activity
      of miconazole against in vitro-grown mature Candida biofilms, and its
      relationship with the induction of ROS and ROS-dependent apoptosis were examined.
      METHODS: The effect of miconazole on mature biofilms formed by 10 C. albicans
      strains and 5 strains from other Candida species was evaluated by plate counting
      and measuring the level of ROS induction. MIC tests were performed in the absence
      and presence of ascorbic acid, a quencher of ROS. The apoptotic population in C.
      albicans cells was determined using annexin-Cy3. RESULTS: Miconazole showed a
      significant fungicidal effect against all mature Candida biofilms tested and
      caused elevated ROS levels, both in planktonic and sessile cells. Addition of
      ascorbic acid drastically reduced these levels. While ROS quenching decreased the
      susceptibility to miconazole of planktonic cells of most Candida strains, no
      reduced fungicidal activity of miconazole against biofilms was observed.
      Miconazole did not cause a significant increase in apoptosis. CONCLUSIONS: ROS
      levels increased in all Candida biofilms upon addition of miconazole. However,
      ROS induction was not the only factor that underlies its fungicidal activity, as
      quenching of ROS did not lead to an enhanced survival of biofilm cells. ROS
      induced apoptosis was not observed in C. albicans cells after miconazole
      treatment.

PMID- 20130025
TI  - Antibiotic susceptibility profiles of European Bacteroides fragilis with reduced
      carbapenem susceptibility.

PMID- 20130026
TI  - In vitro interaction of posaconazole with calcineurin inhibitors and sirolimus
      against zygomycetes.
AB  - OBJECTIVES: Zygomycosis is an uncommon but devastating disease with few
      therapeutic options. Calcineurin inhibitors and sirolimus (mTOR inhibitor),
      commonly used in transplant patients as immunosuppressives, have antifungal
      activity. They are known to demonstrate synergy with triazoles against certain
      fungi, though limited data exist about their activity against zygomycetes. Our
      aim was to study the in vitro interaction of posaconazole with calcineurin
      inhibitors and sirolimus against zygomycetes. METHODS: Drug interactions were
      assessed with chequerboard dilution for posaconazole with calcineurin inhibitors
      and sirolimus according to the CLSI M38-A2 method for filamentous fungi. Twenty
      eight clinical isolates were studied, including Rhizopus arrhizus, Rhizopus
      microsporus, Rhizomucor pusillus, Mucor sp., Cunninghamella bertholletiae,
      Myocladus corymbifera and Apophysomyces elegans. Combinations of posaconazole
      with tacrolimus, cyclosporin A or sirolimus were used. Experiments were performed
      in duplicate. Mean fractional inhibitory concentration indices were calculated.
      RESULTS: Posaconazole with calcineurin inhibitors demonstrated consistent synergy
      against C. bertholletiae, M. corymbifera and A. elegans, whereas synergy or no
      interaction was primarily observed against R. arrhizus, R. microsporus, R.
      pusillus and Mucor. Antagonism was seen with the combination of posaconazole and
      sirolimus. Strain variability was noted among the same species. CONCLUSIONS: The
      clinical significance of these findings is unclear, but further studies are
      warranted given the potential for concomitant use of these agents in transplant
      patients treated for zygomycosis.

PMID- 20130027
TI  - Visualizing SNP statistics in the context of linkage disequilibrium using LD
      Plus.
AB  - SUMMARY: Often in human genetic analysis, multiple tables of single nucleotide
      polymorphism (SNP) statistics are shown alongside a Haploview style correlation
      plot. Readers are then asked to make inferences that incorporate knowledge across
      these multiple sets of results. To better facilitate a collective understanding
      of all available data, we developed a Ruby-based web application, LD-Plus, to
      generate figures that simultaneously display physical location of SNPs, binary
      SNP attributes (such as coding/non-coding or presence on genotyping platforms),
      common haplotypes and their frequencies and continuously scaled values (such as
      F(st), minor allele frequency, genotyping efficiency or P-values), all in the
      context of the D' and r(2) linkage disequilibrium structures. Combining these
      results into one comprehensive figure reduces dereferencing between figures and
      tables, and can provide unique insights into genetic features that are not
      clearly seen when results are partitioned across multiple figures and tables.

PMID- 20130028
TI  - A visual framework for sequence analysis using n-grams and spectral
      rearrangement.
AB  - MOTIVATION: Protein sequences are often composed of regions that have distinct
      evolutionary histories as a consequence of domain shuffling, recombination or
      gene conversion. New approaches are required to discover, visualize and analyze
      these sequence regions and thus enable a better understanding of protein
      evolution. RESULTS: Here, we have developed an alignment-free and visual approach
      to analyze sequence relationships. We use the number of shared n-grams between
      sequences as a measure of sequence similarity and rearrange the resulting
      affinity matrix applying a spectral technique. Heat maps of the affinity matrix
      are employed to identify and visualize clusters of related sequences or outliers,
      while n-gram-based dot plots and conservation profiles allow detailed analysis of
      similarities among selected sequences. Using this approach, we have identified
      signatures of domain shuffling in an otherwise poorly characterized family, and
      homology clusters in another. We conclude that this approach may be generally
      useful as a framework to analyze related, but highly divergent protein sequences.
      It is particularly useful as a fast method to study sequence relationships prior
      to much more time-consuming multiple sequence alignment and phylogenetic
      analysis. AVAILABILITY: A software implementation (MOSAIC) of the framework
      described here can be downloaded from http://bioinformatics.org.au/mosaic/
      CONTACT: m.ragan@uq.edu.au SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 20130029
TI  - Small-sample precision of ROC-related estimates.
AB  - MOTIVATION: The receiver operator characteristic (ROC) curves are commonly used
      in biomedical applications to judge the performance of a discriminant across
      varying decision thresholds. The estimated ROC curve depends on the true positive
      rate (TPR) and false positive rate (FPR), with the key metric being the area
      under the curve (AUC). With small samples these rates need to be estimated from
      the training data, so a natural question arises: How well do the estimates of the
      AUC, TPR and FPR compare with the true metrics? RESULTS: Through a simulation
      study using data models and analysis of real microarray data, we show that (i)
      for small samples the root mean square differences of the estimated and true
      metrics are considerable; (ii) even for large samples, there is only weak
      correlation between the true and estimated metrics; and (iii) generally, there is
      weak regression of the true metric on the estimated metric. For classification
      rules, we consider linear discriminant analysis, linear support vector machine
      (SVM) and radial basis function SVM. For error estimation, we consider
      resubstitution, three kinds of cross-validation and bootstrap. Using resampling,
      we show the unreliability of some published ROC results. AVAILABILITY: Companion
      web site at http://compbio.tgen.org/paper_supp/ROC/roc.html CONTACT:
      edward@mail.ece.tamu.edu.

PMID- 20130030
TI  - Identifying biologically relevant differences between metagenomic communities.
AB  - MOTIVATION: Metagenomics is the study of genetic material recovered directly from
      environmental samples. Taxonomic and functional differences between metagenomic
      samples can highlight the influence of ecological factors on patterns of
      microbial life in a wide range of habitats. Statistical hypothesis tests can help
      us distinguish ecological influences from sampling artifacts, but knowledge of
      only the P-value from a statistical hypothesis test is insufficient to make
      inferences about biological relevance. Current reporting practices for pairwise
      comparative metagenomics are inadequate, and better tools are needed for
      comparative metagenomic analysis. RESULTS: We have developed a new software
      package, STAMP, for comparative metagenomics that supports best practices in
      analysis and reporting. Examination of a pair of iron mine metagenomes
      demonstrates that deeper biological insights can be gained using statistical
      techniques available in our software. An analysis of the functional potential of
      'Candidatus Accumulibacter phosphatis' in two enhanced biological phosphorus
      removal metagenomes identified several subsystems that differ between the
      A.phosphatis stains in these related communities, including phosphate metabolism,
      secretion and metal transport. AVAILABILITY: Python source code and binaries are
      freely available from our website at http://kiwi.cs.dal.ca/Software/STAMP
      CONTACT: beiko@cs.dal.ca SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 20130031
TI  - Six Rossmannoid folds, including the Class I aminoacyl-tRNA synthetases, share a
      partial core with the anti-codon-binding domain of a Class II aminoacyl-tRNA
      synthetase.
AB  - MOTIVATION: Similarities in core residue packing provide evidence for divergence
      or convergence not reported using other methods. RESULTS: We apply a new method
      for rapid structure comparison based on Simplicial Neighborhood Analysis of
      Protein Packing (SNAPP) to the diverse structural classification of proteins
      (SCOP) alpha/beta-class of protein folds. The procedure identifies inter-residue
      packing motifs shared by protein pairs from different folds. A threshold of 0.67
      A RMSD for all atoms of corresponding residues ensures inclusion of only highly
      significant similarities comparable with those observed for identical catalytic
      residues in homologues. Many tertiary packing motifs are shared among the three
      classical Rossmannoid folds, as well as thousands of other motifs that occur in
      at least two distinct folds. Merging of neighboring packing motifs facilitated
      recognition of larger, recurrent substructures or cores. The anti-codon-binding
      domain of an archeal aminoacyl-tRNA synthetase (aaRS) was discovered to possess a
      packed core in which eight identical amino acid residues are within 0.55 A RMSD
      of the comparable structure in the FixJ receiver, a member of the Rossmannoid
      family that also includes the CheY signaling protein and flavodoxin-like
      proteins. Further investigation identified close variants of this core in five
      other Rossmannoid folds, including a functionally relevant core in Class Ia
      aminoacyl-tRNA synthetases. Although it is possible that the two essentially
      identical cores in the ProRS anti-codon-binding domain and the FixJ receiver
      converged to the same structure, the consensus core obtained from the structural
      and sequence alignments suggests that all the implicated protein folds descended
      from a simpler ancestral protein in which this core provided nucleotide binding
      and proto-allosteric functions. AVAILABILITY: Programs are available at
      http://staff.vbi.vt.edu/cammer/snapp/download/ IMPLEMENTATION: Programs were
      written in Perl and c and run under Linux. CONTACT: cammer@vbi.vt.edu.

PMID- 20130032
TI  - Maximal conditional chi-square importance in random forests.
AB  - MOTIVATION: High-dimensional data are frequently generated in genome-wide
      association studies (GWAS) and other studies. It is important to identify
      features such as single nucleotide polymorphisms (SNPs) in GWAS that are
      associated with a disease. Random forests represent a very useful approach for
      this purpose, using a variable importance score. This importance score has
      several shortcomings. We propose an alternative importance measure to overcome
      those shortcomings. RESULTS: We characterized the effect of multiple SNPs under
      various models using our proposed importance measure in random forests, which
      uses maximal conditional chi-square (MCC) as a measure of association between a
      SNP and the trait conditional on other SNPs. Based on this importance measure, we
      employed a permutation test to estimate empirical P-values of SNPs. Our method
      was compared to a univariate test and the permutation test using the Gini and
      permutation importance. In simulation, the proposed method performed consistently
      superior to the other methods in identifying of risk SNPs. In a GWAS of age
      related macular degeneration, the proposed method confirmed two significant SNPs
      (at the genome-wide adjusted level of 0.05). Further analysis showed that these
      two SNPs conformed with a heterogeneity model. Compared with the existing
      importance measures, the MCC importance measure is more sensitive to complex
      effects of risk SNPs by utilizing conditional information on different SNPs. The
      permutation test with the MCC importance measure provides an efficient way to
      identify candidate SNPs in GWAS and facilitates the understanding of the etiology
      between genetic variants and complex diseases. CONTACT: heping.zhang@yale.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 20130033
TI  - Cascleave: towards more accurate prediction of caspase substrate cleavage sites.
AB  - MOTIVATION: The caspase family of cysteine proteases play essential roles in key
      biological processes such as programmed cell death, differentiation,
      proliferation, necrosis and inflammation. The complete repertoire of caspase
      substrates remains to be fully characterized. Accordingly, systematic
      computational screening studies of caspase substrate cleavage sites may provide
      insight into the substrate specificity of caspases and further facilitating the
      discovery of putative novel substrates. RESULTS: In this article we develop an
      approach (termed Cascleave) to predict both classical (i.e. following a P(1) Asp)
      and non-typical caspase cleavage sites. When using local sequence-derived
      profiles, Cascleave successfully predicted 82.2% of the known substrate cleavage
      sites, with a Matthews correlation coefficient (MCC) of 0.667. We found that
      prediction performance could be further improved by incorporating information
      such as predicted solvent accessibility and whether a cleavage sequence lies in a
      region that is most likely natively unstructured. Novel bi-profile Bayesian
      signatures were found to significantly improve the prediction performance and
      yielded the best performance with an overall accuracy of 87.6% and a MCC of
      0.747, which is higher accuracy than published methods that essentially rely on
      amino acid sequence alone. It is anticipated that Cascleave will be a powerful
      tool for predicting novel substrate cleavage sites of caspases and shedding new
      insights on the unknown caspase-substrate interactivity relationship.
      AVAILABILITY: http://sunflower.kuicr.kyoto-u.ac.jp/ approximately sjn/Cascleave/
      CONTACT: jiangning.song@med.monash.edu.au; takutsu@kuicr.kyoto-u.ac.jp; james;
      whisstock@med.monash.edu.au SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 20130034
TI  - Improving protein secondary structure prediction using a simple k-mer model.
AB  - MOTIVATION: Some first order methods for protein sequence analysis inherently
      treat each position as independent. We develop a general framework for
      introducing longer range interactions. We then demonstrate the power of our
      approach by applying it to secondary structure prediction; under the independence
      assumption, sequences produced by existing methods can produce features that are
      not protein like, an extreme example being a helix of length 1. Our goal was to
      make the predictions from state of the art methods more realistic, without loss
      of performance by other measures. RESULTS: Our framework for longer range
      interactions is described as a k-mer order model. We succeeded in applying our
      model to the specific problem of secondary structure prediction, to be used as an
      additional layer on top of existing methods. We achieved our goal of making the
      predictions more realistic and protein like, and remarkably this also improved
      the overall performance. We improve the Segment OVerlap (SOV) score by 1.8%, but
      more importantly we radically improve the probability of the real sequence given
      a prediction from an average of 0.271 per residue to 0.385. Crucially, this
      improvement is obtained using no additional information. AVAILABILITY:
      http://supfam.cs.bris.ac.uk/kmer

PMID- 20130035
TI  - SNVMix: predicting single nucleotide variants from next-generation sequencing of
      tumors.
AB  - MOTIVATION: Next-generation sequencing (NGS) has enabled whole genome and
      transcriptome single nucleotide variant (SNV) discovery in cancer. NGS produces
      millions of short sequence reads that, once aligned to a reference genome
      sequence, can be interpreted for the presence of SNVs. Although tools exist for
      SNV discovery from NGS data, none are specifically suited to work with data from
      tumors, where altered ploidy and tumor cellularity impact the statistical
      expectations of SNV discovery. RESULTS: We developed three implementations of a
      probabilistic Binomial mixture model, called SNVMix, designed to infer SNVs from
      NGS data from tumors to address this problem. The first models allelic counts as
      observations and infers SNVs and model parameters using an expectation
      maximization (EM) algorithm and is therefore capable of adjusting to deviation of
      allelic frequencies inherent in genomically unstable tumor genomes. The second
      models nucleotide and mapping qualities of the reads by probabilistically
      weighting the contribution of a read/nucleotide to the inference of a SNV based
      on the confidence we have in the base call and the read alignment. The third
      combines filtering out low-quality data in addition to probabilistic weighting of
      the qualities. We quantitatively evaluated these approaches on 16 ovarian cancer
      RNASeq datasets with matched genotyping arrays and a human breast cancer genome
      sequenced to >40x (haploid) coverage with ground truth data and show
      systematically that the SNVMix models outperform competing approaches.
      AVAILABILITY: Software and data are available at http://compbio.bccrc.ca CONTACT:
      sshah@bccrc.ca SUPPLEMANTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 20130036
TI  - Reach adaptation and proprioceptive recalibration following exposure to
      misaligned sensory input.
AB  - Motor adaptation in response to a visuomotor distortion arises when the usual
      motor command no longer results in the predicted sensory output. In this study,
      we examined if exposure to a sensory discrepancy was sufficient on its own to
      produce changes in reaches and recalibrate the sense of felt hand position in the
      absence of any voluntary movements. Subjects pushed their hand out along a robot
      generated fixed linear path (active exposure group) or were passively moved along
      the same path (passive exposure group). This fixed path was gradually rotated
      counterclockwise around the home position with respect to the path of the cursor.
      On all trials, subjects saw the cursor head directly to the remembered target
      position while their hand moved outwards. We found that after exposure to the
      visually distorted hand motion, subjects in both groups adapted their reaches
      such that they aimed ~6 degrees  to the left of the intended target. The
      magnitude of reach adaptation was similar to the extent that subjects
      recalibrated their sense of felt hand position. Specifically the position at
      which subjects perceived their unseen hand to be aligned with a reference marker
      was the same as that to which they reached when allowed to move freely. Given the
      similarity in magnitude of these adaptive responses we propose that reach
      adaptation arose due to changes in subjects' sense of felt hand position.
      Moreover, results indicate that motor adaptation can arise following exposure to
      a sensory mismatch in the absence of movement related error signals.

PMID- 20130037
TI  - Sensations evoked by microstimulation of single mechanoreceptive afferents
      innervating the human face and mouth.
AB  - Intraneural microneurography and microstimulation were performed on single
      afferent axons in the inferior alveolar and lingual nerves innervating the face,
      teeth, labial, or oral mucosa. Using natural mechanical stimuli, 35 single
      mechanoreceptive afferents were characterized with respect to unit type [fast
      adapting type I (FA I), FA hair, slowly adapting type I and II (SA I and SA II),
      periodontal, and deep tongue units] as well as size and shape of the receptive
      field. All afferents were subsequently microstimulated with pulse trains at 30 Hz
      lasting 1.0 s. Afferents recordings whose were stable thereafter were also tested
      with single pulses and pulse trains at 5 and 60 Hz. The results revealed that
      electrical stimulation of single FA I, FA hair, and SA I afferents from the
      orofacial region can evoke a percept that is spatially matched to the afferent's
      receptive field and consistent with the afferent's response properties as
      observed on natural mechanical stimulation. Stimulation of FA afferents typically
      evoked sensations that were vibratory in nature; whereas those of SA I afferents
      were felt as constant pressure. These afferents terminate superficially in the
      orofacial tissues and seem to have a particularly powerful access to perceptual
      levels. In contrast, microstimulation of single periodontal, SA II, and deep
      tongue afferents failed to evoke a sensation that matched the receptive field of
      the afferent. These afferents terminate more deeply in the tissues, are often
      active in the absence of external stimulation, and probably access perceptual
      levels only when multiple afferents are stimulated. It is suggested that the
      spontaneously active afferents that monitor tension in collagen fibers (SA II and
      periodontal afferents) may have the role to register the mechanical state of the
      soft tissues, which has been hypothesized to help maintain the body's
      representation in the central somatosensory system.

PMID- 20130038
TI  - Fastigial oculomotor region and the control of foveation during fixation.
AB  - When primates maintain their gaze directed toward a visual target (visual
      fixation), their eyes display a combination of miniature fast and slow movements.
      An involvement of the cerebellum in visual fixation is indicated by the severe
      gaze instabilities observed in patients suffering from cerebellar lesions. Recent
      studies in non-human primates have identified a cerebellar structure, the
      fastigial oculomotor region (FOR), as a major cerebellar output nucleus with
      projections toward oculomotor regions in the brain stem. Unilateral inactivation
      of the FOR leads to dysmetric visually guided saccades and to an offset in gaze
      direction when the animal fixates a visual target. However, the nature of this
      fixation offset is not fully understood. In the present work, we analyze the
      inactivation-induced effects on fixation. A novel technique is adopted to
      describe the generation of saccades when a target is being fixated (fixational
      saccades). We show that the offset is the result of a combination of impaired
      saccade accuracy and an altered encoding of the foveal target position. Because
      they are independent, we propose that these two impairments are mediated by the
      different projections of the FOR to the brain stem, in particular to the deep
      superior colliculus and the pontomedullary reticular formation. Our study
      demonstrates that the oculomotor cerebellum, through the activity in the FOR,
      regulates both the amplitude of fixational saccades and the position toward which
      the eyes must be directed, suggesting an involvement in the acquisition of visual
      information from the fovea.

PMID- 20130039
TI  - Cerebellar cortex contributions to the expression and timing of conditioned
      eyelid responses.
AB  - We used micro-infusions during eyelid conditioning in rabbits to investigate the
      relative contributions of cerebellar cortex and the underlying deep nuclei (DCN)
      to the expression of cerebellar learning. These tests were conducted using two
      forms of cerebellum-dependent eyelid conditioning for which the relative roles of
      cerebellar cortex and DCN are controversial: delay conditioning, which is largely
      unaffected by forebrain lesions, and trace conditioning, which involves
      interactions between forebrain and cerebellum. For rabbits trained with delay
      conditioning, silencing cerebellar cortex by micro-infusions of the local
      anesthetic lidocaine unmasked stereotyped short-latency responses. This was also
      the case after extinction as observed previously with reversible blockade of
      cerebellar cortex output. Conversely, increasing cerebellar cortex activity by
      micro-infusions of the GABA(A) antagonist picrotoxin reversibly abolished
      conditioned responses. Effective cannula placements were clustered around the
      primary fissure and deeper in lobules hemispheric lobule IV (HIV) and hemispheric
      lobule V (HV) of anterior lobe. In well-trained trace conditioned rabbits,
      silencing this same area of cerebellar cortex or reversibly blocking cerebellar
      cortex output also unmasked short-latency responses. Because Purkinje cells are
      the sole output of cerebellar cortex, these results provide evidence that the
      expression of well-timed conditioned responses requires a well-timed decrease in
      the activity of Purkinje cells in anterior lobe. The parallels between results
      from delay and trace conditioning suggest similar contributions of plasticity in
      cerebellar cortex and DCN in both instances.

PMID- 20130040
TI  - High precision and fast functional mapping of cortical circuitry through a novel
      combination of voltage sensitive dye imaging and laser scanning photostimulation.
AB  - The development of modern neuroscience tools is critical for deciphering brain
      circuit organization and function. An important aspect for technical development
      is to enhance each technique's advantages and compensate for limitations. We
      developed a high-precision and fast functional mapping technique in brain slices
      that incorporates the spatial precision of activation that can be achieved by
      laser-scanning photostimulation with rapid and high-temporal resolution
      assessment of evoked network activity that can be achieved by voltage-sensitive
      dye imaging. Unlike combination of whole cell recordings with photostimulation
      for mapping local circuit inputs to individually recorded neurons, this
      innovation is a new photostimulation-based technique to map cortical circuit
      output and functional connections at the level of neuronal populations. Here we
      report on this novel technique in detail and show its effective applications in
      mapping functional connections and circuit dynamics in mouse primary visual
      cortex and hippocampus. Given that this innovation enables rapid mapping and
      precise evaluation of cortical organization and function, it can have broad
      impacts in the field of cortical circuitry.

PMID- 20130041
TI  - Differential effects of reflex blinks on saccade perturbations in humans.
AB  - Studies in both humans and monkeys have indicated that blinks affect the central
      programming of saccades. In this study, we compared the influence of two types of
      reflex blinks on the trajectories and kinematics of memory-guided saccades in
      human subjects. We found that electrical stimulation of the supraorbital nerve
      shortly before or during a saccade briefly halts or decelerates the eye in
      midflight. After this short interruption, the eye always resumed its course and
      reached the target location in the absence of visual feedback. Air puff stimuli
      produced significant decreases in mean eye velocity too, but in addition to these
      changes in saccade kinematics, they produced much larger and more variable
      perturbations of the two-dimensional saccade trajectories. Even so, the endpoints
      of blink-perturbed saccades obtained under both test conditions remained as
      accurate and as precise as those observed in the control condition. We
      hypothesize that the reduction in mean eye velocity is not caused by a trigeminal
      reactivation of brain stem omnipause neurons but could instead arise from a
      trigeminal transient inhibition of saccade-related activity in the midbrain
      superior colliculus (SC). These findings support the theory that blink-perturbed
      saccades are programmed as slow, but straight, saccades onto which blink-related
      eye movements are superimposed. This linear superposition occurs downstream from
      the SC.

PMID- 20130042
TI  - Optimal control of a hybrid rhythmic-discrete task: the bouncing ball revisited.
AB  - Rhythmically bouncing a ball with a racket is a hybrid task that combines
      continuous rhythmic actuation of the racket with the control of discrete impact
      events between racket and ball. This study presents experimental data and a two
      layered modeling framework that explicitly addresses the hybrid nature of
      control: a first discrete layer calculates the state to reach at impact and the
      second continuous layer smoothly drives the racket to this desired state, based
      on optimality principles. The testbed for this hybrid model is task performance
      at a range of increasingly slower tempos. When slowing the rhythm of the bouncing
      actions, the continuous cycles become separated into a sequence of discrete
      movements interspersed by dwell times and directed to achieve the desired impact.
      Analyses of human performance show increasing variability of performance measures
      with slower tempi, associated with a change in racket trajectories from
      approximately sinusoidal to less symmetrical velocity profiles. Matching results
      of model simulations give support to a hybrid control model based on optimality,
      and therefore suggest that optimality principles are applicable to the
      sensorimotor control of complex movements such as ball bouncing.

PMID- 20130043
TI  - Activity-dependent layer-specific changes in the extracellular chloride
      concentration and chloride driving force in the rat hippocampus.
AB  - The transmembrane distribution of chloride anions (Cl-) determines the direction
      of the Cl- flux through GABA(A) receptors; this establishes whether GABA(A)
      receptor-mediated responses are hyperpolarizing or depolarizing in neurons. Thus
      an activity-dependent reduction in the efficacy of inhibitory responses can be
      the result of an activity-induced reduction of the Cl- driving force. Using Cl(-)
      sensitive electrodes, we measured the extracellular Cl- concentration ([Cl-](o))
      in each layer of the hippocampus under control conditions and after stimulation.
      In the control condition, [Cl-](o) was lower within the CA1 region (112.9 +/- 1.3
      mM; mean +/- SD) than the CA3/dentate gyrus areas (117.7 +/- 1.2 mM). Stimulation
      of CA3 pyramidal cells led to an increase in the [Cl-](o). The maximum values
      were observed in the stratum lacunosum-moleculare (253.4 +/- 51.1 mM) and in the
      hilus (261 +/- 43.7 mM), whereas in the granular cell layer, it reached only
      159.5 +/- 41 mM. The stimulation-induced [Cl-](o) increase was followed by a
      period of decreasing [Cl-](o) that fell below the control values. The maximum
      undershoot (21.6 +/- 0.7 mM) was observed in the s. radiatum. Systemic
      application of the gap junction blocker carbenoxolone significantly decreased the
      stimulation-induced Cl- extrusion in the dentate gyrus but only slightly modified
      it in the CA1 area. Carbenoxolone also drastically reduced the Cl- clearance. The
      time constant of the Cl- clearance was similar between layers (83.4 +/- 15.9 ms)
      but increased after carbenoxolone application (207.1 +/- 44.4 ms). Stimulation
      induced changes in the [Cl-](o) significantly decreased the Cl- driving force and
      resulted in large fluctuations between layers (Delta = 9.4 mV). The lowest value
      was observed in the stratum radiatum of the CA1 and the hilar region (7.7 mV),
      whereas the highest value was calculated for the granule cell layer (16.3 mV). We
      suggest that a decrease of the extracellular space is mainly responsible for the
      rapid [Cl-](o) increase while the gap junction coupled astrocytic network plays a
      key role in the activity-dependent redistribution and clearance of Cl- across
      layers of the hippocampus.

PMID- 20130044
TI  - The responses of VIP neurons are sufficiently sensitive to support heading
      judgments.
AB  - The ventral intraparietal area (VIP) of the macaque monkey is thought to be
      involved in judging heading direction based on optic flow. We recorded neuronal
      discharges in VIP while monkeys were performing a two-alternative, forced-choice
      heading discrimination task to relate quantitatively the activity of VIP neurons
      to monkeys' perceptual choices. Most VIP neurons were responsive to simulated
      heading stimuli and were tuned such that their responses changed across a range
      of forward trajectories. Using receiver operating characteristic (ROC) analysis,
      we found that most VIP neurons were less sensitive to small heading changes than
      was the monkey, although a minority of neurons were equally sensitive. Pursuit
      eye movements modestly yet significantly increased both neuronal and behavioral
      thresholds by approximately the same amount. Our results support the view that
      VIP activity is involved in self-motion judgments.

PMID- 20130045
TI  - Antisense transcription in gammaretroviruses as a mechanism of insertional
      activation of host genes.
AB  - Transcription of retroviruses is initiated at the U3-R region boundary in the
      integrated provirus and continues unidirectionally to produce genomic and mRNA
      products of positive polarity. Several studies have recently demonstrated the
      existence of naturally occurring protein-encoding transcripts of negative
      polarity in complex retroviruses. We report here on the identification of
      transcripts of negative polarity in simple murine leukemia virus (MLV). In T-cell
      and B-cell lymphomas induced by SL3-3 and Akv MLV, antisense transcripts
      initiated in the U3 region of the proviral 5' long terminal repeat (LTR) and
      continued into the cellular proto-oncogenes Jdp2 and Bach2 to create chimeric
      transcripts consisting of viral and host sequence. The phenomenon was validated
      in vivo using a knock-in mouse model homozygous for a single LTR at a position
      known to activate Nras in B-cell lymphomas. A 5' rapid amplification of cDNA ends
      (RACE) analysis indicated a broad spectrum of initiation sites within the U3
      region of the 5' LTR. Our data show for the first time transcriptional activity
      of negative polarity initiating in the U3 region of simple retroviruses and
      suggest a novel mechanism of insertional activation of host genes. Elucidation of
      the nature and potential regulatory role of 5' LTR antisense transcription will
      be relevant to the design of therapeutic vectors and may contribute to the
      increasing recognition of pervasive eukaryotic transcription.

PMID- 20130046
TI  - Impact of varicella-zoster virus on dendritic cell subsets in human skin during
      natural infection.
AB  - Varicella-zoster virus (VZV) causes varicella and herpes zoster, diseases
      characterized by distinct cutaneous rashes. Dendritic cells (DC) are essential
      for inducing antiviral immune responses; however, the contribution of DC subsets
      to immune control during natural cutaneous VZV infection has not been
      investigated. Immunostaining showed that compared to normal skin, the proportion
      of cells expressing DC-SIGN (a dermal DC marker) or DC-LAMP and CD83 (mature DC
      markers) were not significantly altered in infected skin. In contrast, the
      frequency of Langerhans cells was significantly decreased in VZV-infected skin,
      whereas there was an influx of plasmacytoid DC, a potent secretor of type I
      interferon (IFN). Langerhans cells and plasmacytoid DC in infected skin were
      closely associated with VZV antigen-positive cells, and some Langerhans cells and
      plasmacytoid DC were VZV antigen positive. To extend these in vivo observations,
      both plasmacytoid DC (PDC) isolated from human blood and Langerhans cells derived
      from MUTZ-3 cells were shown to be permissive to VZV infection. In VZV-infected
      PDC cultures, significant induction of alpha IFN (IFN-alpha) did not occur,
      indicating the VZV inhibits the capacity of PDC to induce expression of this host
      defense cytokine. This study defines changes in the response of DC which occur
      during cutaneous VZV infection and implicates infection of DC subtypes in VZV
      pathogenesis.

PMID- 20130047
TI  - Direct evidence from single-cell analysis that human {alpha}-defensins block
      adenovirus uncoating to neutralize infection.
AB  - Human alpha-defensins are evolutionarily conserved effectors of the innate immune
      response with broadly acting antibacterial activity. Their role in antiviral
      immunity is less well understood. We previously showed that these antimicrobial
      peptides are potent inhibitors of human adenovirus infection. Based on
      biochemical studies and indirect evidence from confocal microscopy, we proposed
      that defensins bind to and stabilize the virus capsid and neutralize infection by
      preventing the release of the endosomalytic protein VI. To determine whether
      defensin action also restricts exposure of the viral genome, we developed a
      system to evaluate adenovirus uncoating during cell entry by monitoring the
      exposure of BrdU-labeled viral genomes. This assay allowed us to determine the
      kinetics of uncoating of virus particles in single cells. Using this assay, we
      now provide direct evidence that human alpha-defensins block adenovirus infection
      by preventing uncoating during cell entry.

PMID- 20130048
TI  - Bimolecular complementation defines functional regions of Herpes simplex virus gB
      that are involved with gH/gL as a necessary step leading to cell fusion.
AB  - Herpes simplex virus (HSV) entry into cells requires four membrane glycoproteins:
      gD is the receptor binding protein, and gB and gH/gL constitute the core fusion
      machinery. Crystal structures of gD and its receptors have provided a basis for
      understanding the initial triggering steps, but how the core fusion proteins
      function remains unknown. The gB crystal structure shows that it is a class III
      fusion protein, yet unlike other class members, gB itself does not cause fusion.
      Bimolecular complementation (BiMC) studies have shown that gD-receptor binding
      triggers an interaction between gB and gH/gL and concurrently triggers fusion.
      Left unanswered was whether BiMC led to fusion or was a by-product of it. We used
      gB monoclonal antibodies (MAbs) to block different aspects of these events. Non
      virus-neutralizing MAbs to gB failed to block BiMC or fusion. In contrast, gB
      MAbs that neutralize virus blocked fusion. These MAbs map to three functional
      regions (FR) of gB. MAbs to FR1, which contains the fusion loops, and FR2 blocked
      both BiMC and fusion. In contrast, MAbs to FR3, a region involved in receptor
      binding, blocked fusion but not BiMC. Thus, FR3 MAbs separate the BiMC
      interaction from fusion, suggesting that BiMC occurs prior to fusion. When
      substituted for wild-type (wt) gB, fusion loop mutants blocked fusion and BiMC,
      suggesting that loop insertion precedes BiMC. Thus, we postulate that each of the
      gB FRs are involved in different aspects of the path leading to fusion. Upon
      triggering by gD, gB fusion loops are inserted into target lipid membranes. gB
      then interacts with gH/gL, and this interaction is eventually followed by fusion.

PMID- 20130049
TI  - The pre-s2 domain of the hepatitis B virus is dispensable for infectivity but
      serves a spacer function for L-protein-connected virus assembly.
AB  - The envelope of the human hepatitis B virus (HBV) contains three membrane
      proteins (L, M, and S). They accomplish different functions in HBV infectivity
      and nucleocapsid envelopment. Infectivity determinants have been assigned to the
      N-terminal part of the pre-S1 domain of the L protein and the antigenic loop of
      the S domain in the L and/or S protein. Nucleocapsid envelopment requires a C
      terminal sequence within pre-S1, including the five N-terminal amino acids of pre
      S2 as part of the L protein. However, the role of the M protein and the pre-S2
      domain of the L protein are not entirely understood. We addressed this question
      and analyzed assembly competence and infectivity of viruses that lack the M
      protein and, at the same time, carry alterations in the pre-S2 domain of L. These
      include deletions, in part frameshift mutations and a randomization of virtually
      the entire pre-S2 sequence. We found that the M protein is dispensable for HBV in
      vitro infectivity. Viruses that lack the M protein and contain a mostly
      randomized pre-S2 sequence assemble properly and are infectious in HepaRG cells
      and primary human hepatocytes. While deletions of 20 amino acids in the pre-S2
      domain of L protein allowed the production of infectious virions, more extended
      deletions interfered with assembly. This indicates that the pre-S2 domain of the
      L protein serves an important role for virus assembly, presumably as a spacer
      that supports conformational changes of L protein but does not participate as
      part of the M protein or as a subdomain of the L protein in virus entry.

PMID- 20130050
TI  - Killing of avian and Swine influenza virus by natural killer cells.
AB  - Today, global attention is focused on two influenza virus strains: the current
      pandemic strain, swine origin influenza virus (H1N1-2009), and the highly
      pathogenic avian influenza virus, H5N1. At present, the infection caused by the
      H1N1-2009 is moderate, with mortality rates of less <1%. In contrast, infection
      with the H5N1 virus resulted in high mortality rates, and ca. 60% of the infected
      patients succumb to the infection. Thus, one of the world greatest concerns is
      that the H5N1 virus will evolve to allow an efficient human infection and human
      to-human transmission. Natural killer (NK) cells are one of the innate immune
      components playing an important role in fighting against influenza viruses. One
      of the major NK activating receptors involved in NK cell cytotoxicity is NKp46.
      We previously demonstrated that NKp46 recognizes the hemagglutinin proteins of B
      and A influenza virus strains. Whether NKp46 could also interact with H1N1-2009
      virus or with the avian influenza virus is still unknown. We analyzed the
      immunological properties of both the avian and the H1N1-2009 influenza viruses.
      We show that NKp46 recognizes the hemagglutinins of H1N1-2009 and H5 and that
      this recognition leads to virus killing both in vitro and in vivo. However,
      importantly, while the swine H1-NKp46 interactions lead to the direct killing of
      the infected cells, the H5-NKp46 interactions were unable to elicit direct
      killing, probably because the NKp46 binding sites for these two viruses are
      different.

PMID- 20130051
TI  - Role of the IE62 consensus binding site in transactivation by the varicella
      zoster virus IE62 protein.
AB  - The varicella-zoster virus (VZV) IE62 protein is the major transcriptional
      activator. IE62 is capable of associating with DNA both nonspecifically and in a
      sequence-specific manner via a consensus binding site (5'-ATCGT-3'). However, the
      function of the consensus site is poorly understood, since IE62 efficiently
      transactivates promoter elements lacking this sequence. In the work presented
      here, sequence analysis of the VZV genome revealed the presence of 245 IE62
      consensus sites throughout the genome. Some 54 sites were found to be present
      within putative VZV promoters. Electrophoretic mobility shift assay (EMSA)
      experiments using an IE62 fragment containing the IE62 DNA-binding domain and
      duplex oligonucleotides that did or did not contain the IE62 consensus binding
      sequence yielded K(D) (equilibrium dissociation constant) values in the nanomolar
      range. Further, the IE62 DNA binding domain was shown to have a 5-fold-increased
      affinity for its consensus site compared to nonconsensus sequences. The effect of
      consensus site presence and position on IE62-mediated activation of native VZV
      and model promoters was examined using site-specific mutagenesis and transfection
      and superinfection reporter assays. In all promoters examined, the consensus
      sequence functioned as a distance-dependent repressive element. Protein
      recruitment assays utilizing the VZV gI promoter indicated that the presence of
      the consensus site increased the recruitment of IE62 but not Sp1. These data
      suggest a model where the IE62 consensus site functions to down-modulate IE62
      activation, and interaction of IE62 with this sequence may result in loss or
      decrease of the ability of IE62 to recruit cellular factors needed for full
      promoter activation.

PMID- 20130052
TI  - A mouse model of lethal infection for evaluating prophylactics and therapeutics
      against Monkeypox virus.
AB  - Monkeypox virus (MPXV) is an orthopoxvirus closely related to variola, the
      etiological agent of smallpox. In humans, MPXV causes a disease similar to
      smallpox and is considered to be an emerging infectious disease. Moreover, the
      use of MPXV for bioterroristic/biowarfare activities is of significant concern.
      Available small animal models of human monkeypox have been restricted to mammals
      with poorly defined biologies that also have limited reagent availability. We
      have established a murine MPXV model utilizing the STAT1-deficient C57BL/6 mouse.
      Here we report that a relatively low-dose intranasal (IN) infection induces 100%
      mortality in the stat1(-)(/)(-) model by day 10 postinfection with high
      infectious titers in the livers, spleens, and lungs of moribund animals.
      Vaccination with modified vaccinia virus Ankara (MVA) followed by a booster
      vaccination is sufficient to protect against an intranasal MPXV challenge and
      induces an immune response more robust than that of a single vaccination.
      Furthermore, antiviral treatment with CMX001 (HDP-cidofovir) and ST-246 protects
      when administered as a regimen initiated on the day of infection. Thus, the
      stat1(-)(/)(-) model provides a lethal murine platform for evaluating
      therapeutics and for investigating the immunological and pathological responses
      to MPXV infection.

PMID- 20130053
TI  - Dynamics of influenza virus infection and pathology.
AB  - A key question in pandemic influenza is the relative roles of innate immunity and
      target cell depletion in limiting primary infection and modulating pathology.
      Here, we model these interactions using detailed data from equine influenza virus
      infection, combining viral and immune (type I interferon) kinetics with estimates
      of cell depletion. The resulting dynamics indicate a powerful role for innate
      immunity in controlling the rapid peak in virus shedding. As a corollary, cells
      are much less depleted than suggested by a model of human influenza based only on
      virus-shedding data. We then explore how differences in the influence of viral
      proteins on interferon kinetics can account for the observed spectrum of virus
      shedding, immune response, and influenza pathology. In particular, induction of
      high levels of interferon ("cytokine storms"), coupled with evasion of its
      effects, could lead to severe pathology, as hypothesized for some fatal cases of
      influenza.

PMID- 20130054
TI  - Contribution of vaccine-induced immunity toward either the HA or the NA component
      of influenza viruses limits secondary bacterial complications.
AB  - Secondary bacterial infections contribute to morbidity and mortality from
      influenza. Vaccine effectiveness is typically assessed using prevention of
      influenza, not secondary infections, as an endpoint. We vaccinated mice with
      formalin-inactivated influenza virus vaccine preparations containing disparate HA
      and NA proteins and demonstrated an ability to induce the appropriate anti-HA and
      anti-NA immune profiles. Protection from both primary viral and secondary
      bacterial infection was demonstrated with vaccine-induced immunity directed
      toward either the HA or the NA. This finding suggests that immunity toward the NA
      component of the virion is desirable and should be considered in generation of
      influenza vaccines.

PMID- 20130055
TI  - Species-specific inhibition of foamy viruses from South American monkeys by New
      World Monkey TRIM5{alpha} proteins.
AB  - Foamy virus evolution closely parallels that of the host species, indicating
      virus-host coadaptation. We studied simian foamy viruses (SFVs) from common
      marmosets, spider monkeys, and squirrel monkeys, New World monkey (NWM) species
      that share geographic ranges. The TRIM5alpha protein from each of these NWM
      species inhibited the replication of at least one of the SFVs associated with the
      other two species but did not affect the replication of its own SFV. Thus,
      TRIM5alpha has potentially shaped the evolution of SFVs in NWM hosts. Conversely,
      SFVs may have influenced the evolution of TRIM5 variants in New World primates.

PMID- 20130056
TI  - Distinct p53, p53:LANA, and LANA complexes in Kaposi's Sarcoma--associated
      Herpesvirus Lymphomas.
AB  - The role of p53 in primary effusion lymphoma (PEL) is complicated. The latency
      associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus
      (KSHV) binds p53. Despite this interaction, we had found that p53 was functional
      in PEL, i.e., able to induce apoptosis in response to DNA damage (C. E. Petre, S.
      H. Sin, and D. P. Dittmer, J. Virol. 81:1912-1922, 2007), and that hdm2 was
      overexpressed. To further elucidate the relationship between LANA, p53, and hdm2,
      we purified LANA complexes from PEL by column chromatography. This confirmed that
      LANA bound p53. However, the LANA:p53 complexes were a minority compared to
      hdm2:p53 and p53:p53 complexes. The half-life of p53 was not extended, which is
      in contrast to the half-life of simian virus 40 T antigen-transformed cells.
      p53:p53, LANA:p53, and LANA:LANA complexes coexisted in PEL, and each protein was
      able to bind to its cognate DNA element. These data suggest that under normal
      conditions, p53 is inactive in PEL, thus allowing for exponential growth, but
      that this inactivation is driven by the relative stoichiometries of LANA, hdm2,
      and p53. If p53 is activated by DNA damage or nutlin-3a, the complex falls apart
      easily, and p53 exercises its role as guardian of the genome.

PMID- 20130057
TI  - Env-expressing autologous T lymphocytes induce neutralizing antibody and afford
      marked protection against feline immunodeficiency virus.
AB  - The envelope (Env) glycoproteins of HIV and other lentiviruses possess
      neutralization and other protective epitopes, yet all attempts to induce
      protective immunity using Env as the only immunogen have either failed or
      afforded minimal levels of protection. In a novel prime-boost approach, specific
      pathogen-free cats were primed with a plasmid expressing Env of feline
      immunodeficiency virus (FIV) and feline granulocyte-macrophage colony-stimulating
      factor and then boosted with their own T lymphocytes transduced ex vivo to
      produce the same Env and interleukin 15 (3 x 10(6) to 10 x 10(6) viable
      cells/cat). After the boost, the vaccinees developed elevated immune responses,
      including virus-neutralizing antibodies (NA). Challenge with an ex vivo
      preparation of FIV readily infected all eight control cats (four mock vaccinated
      and four naive) and produced a marked decline in the proportion of peripheral CD4
      T cells. In contrast, five of seven vaccinees showed little or no traces of
      infection, and the remaining two had reduced viral loads and underwent no changes
      in proportions of CD4 T cells. Interestingly, the viral loads of the vaccinees
      were inversely correlated to the titers of NA. The findings support the concept
      that Env is a valuable immunogen but needs to be administered in a way that
      permits the expression of its full protective potential.

PMID- 20130058
TI  - The ORF3 protein of hepatitis E virus delays degradation of activated growth
      factor receptors by interacting with CIN85 and blocking formation of the Cbl
      CIN85 complex.
AB  - Hepatitis E virus (HEV) causes an acute self-limiting disease that is endemic in
      developing countries. Previous studies suggested that the ORF3 protein (pORF3) of
      HEV is required for infection in vivo and is likely to modulate the host
      response. Our previous work showed that pORF3 localizes to early and recycling
      endosomes and causes a delay in the postinternalization trafficking of epidermal
      growth factor receptor (EGFR) to late endosomes/lysosomes. Here we report that
      pORF3 also delays the trafficking and degradation of activated hepatocyte growth
      factor receptor (c-Met) and delineate the mechanistic details of these effects. A
      mutant ORF3 protein, which does not localize to endosomes, also showed similar
      effects on growth factor receptor trafficking, making this effect independent of
      the endosomal localization of pORF3. The ORF3 protein was found to interact with
      CIN85, a multidomain adaptor protein implicated in the Cbl-mediated
      downregulation of receptor tyrosine kinases. This interaction competed with the
      formation of the growth factor receptor-Cbl-CIN85 complex, resulting in the
      reduced ubiquitination of CIN85 and trafficking of the growth factor receptor
      complex toward late endosomes/lysosomes. We propose that through its effects on
      growth factor receptor trafficking, pORF3 prolongs endomembrane growth factor
      signaling and promotes cell survival to contribute positively to viral
      replication and pathogenesis.

PMID- 20130059
TI  - Proliferation capacity and cytotoxic activity are mediated by functionally and
      phenotypically distinct virus-specific CD8 T cells defined by interleukin
      7R{alpha} (CD127) and perforin expression.
AB  - Cytotoxicity and proliferation capacity are key functions of antiviral CD8 T
      cells. In the present study, we investigated a series of markers to define these
      functions in virus-specific CD8 T cells. We provide evidence that there is a lack
      of coexpression of perforin and CD127 in human CD8 T cells. CD127 expression on
      virus-specific CD8 T cells correlated positively with proliferation capacity and
      negatively with perforin expression and cytotoxicity. Influenza virus-,
      cytomegalovirus-, and Epstein-Barr virus/human immunodeficiency virus type 1
      specific CD8 T cells were predominantly composed of CD127(+) perforin(-)/CD127(-)
      perforin(+), and CD127(-)/perforin(-) CD8 T cells, respectively. CD127(
      )/perforin(-) and CD127(-)/perforin(+) cells expressed significantly more PD-1
      and CD57, respectively. Consistently, intracellular cytokine (gamma interferon,
      tumor necrosis factor alpha, and interleukin-2 [IL-2]) responses combined to
      perforin detection confirmed that virus-specific CD8 T cells were mostly composed
      of either perforin(+)/IL-2(-) or perforin(-)/IL-2(+) cells. In addition, perforin
      expression and IL-2 secretion were negatively correlated in virus-specific CD8 T
      cells (P < 0.01). As previously shown for perforin, changes in antigen exposure
      modulated also CD127 expression. Based on the above results, proliferating
      (CD127(+)/IL-2-secreting) and cytotoxic (perforin(+)) CD8 T cells were contained
      within phenotypically distinct T-cell populations at different stages of
      activation or differentiation and showed different levels of exhaustion and
      senescence. Furthermore, the composition of proliferating and cytotoxic CD8 T
      cells for a given antiviral CD8 T-cell population appeared to be influenced by
      antigen exposure. These results advance our understanding of the relationship
      between cytotoxicity, proliferation capacity, the levels of senescence and
      exhaustion, and antigen exposure of antiviral memory CD8 T cells.

PMID- 20130060
TI  - Human rhinovirus 14 enters rhabdomyosarcoma cells expressing icam-1 by a clathrin
      , caveolin-, and flotillin-independent pathway.
AB  - Intercellular adhesion molecule 1 (ICAM-1) mediates binding and entry of major
      group human rhinoviruses (HRVs). Whereas the entry pathway of minor group HRVs
      has been studied in detail and is comparatively well understood, the pathway
      taken by major group HRVs is largely unknown. Use of immunofluorescence
      microscopy, colocalization with specific endocytic markers, dominant negative
      mutants, and pharmacological inhibitors allowed us to demonstrate that the major
      group virus HRV14 enters rhabdomyosarcoma cells transfected to express human ICAM
      1 in a clathrin-, caveolin-, and flotillin-independent manner. Electron
      microscopy revealed that many virions accumulated in long tubular structures,
      easily distinguishable from clathrin-coated pits and caveolae. Virus entry was
      strongly sensitive to the Na(+)/H(+) ion exchange inhibitor amiloride and
      moderately sensitive to cytochalasin D. Thus, cellular uptake of HRV14 occurs via
      a pathway exhibiting some, but not all, characteristics of macropinocytosis and
      is similar to that recently described for adenovirus 3 entry via alpha(v)
      integrin/CD46 in HeLa cells.

PMID- 20130061
TI  - Caulimoviridae tubule-guided transport is dictated by movement protein
      properties.
AB  - Plant viruses move through plasmodesmata (PD) either as nucleoprotein complexes
      (NPCs) or as tubule-guided encapsidated particles with the help of movement
      proteins (MPs). To explore how and why MPs specialize in one mechanism or the
      other, we tested the exchangeability of MPs encoded by DNA and RNA virus genomes
      by means of an engineered alfalfa mosaic virus (AMV) system. We show that
      Caulimoviridae (DNA genome virus) MPs are competent for RNA virus particle
      transport but are unable to mediate NPC movement, and we discuss this restriction
      in terms of the evolution of DNA virus MPs as a means of mediating DNA viral
      genome entry into the RNA-trafficking PD pathway.

PMID- 20130062
TI  - Pathogenesis of a model gammaherpesvirus in a natural host.
AB  - Murine gammaherpesvirus 68 (MHV-68) infection of laboratory mice (Mus musculus)
      is an established model of gammaherpesvirus pathogenesis. The fact that M.
      musculus is not a host in the wild prompted us to reassess MHV-68 infection in
      wood mice (Apodemus sylvaticus), a natural host. Here, we report significant
      differences in MHV-68 infection in the two species: (i) following intranasal
      inoculation, MHV-68 replicated in the lungs of wood mice to levels approximately
      3 log units lower than in BALB/c mice; (ii) in BALB/c mice, virus replication in
      alveolar epithelial cells was accompanied by a diffuse, T-cell-dominated
      interstitial pneumonitis, whereas in wood mice it was restricted to focal
      granulomatous infiltrations; (iii) within wood mice, latently infected
      lymphocytes were abundant in inducible bronchus-associated lymphoid tissue that
      was not apparent in BALB/c mice; (iv) splenic latency was established in both
      species, but well-delineated secondary follicles with germinal centers were
      present in wood mice, while only poorly delineated follicles were seen in BALB/c
      mice; and, perhaps as a consequence, (v) production of neutralizing antibody was
      significantly higher in wood mice. These differences highlight the value of this
      animal model in the study of MHV-68 pathogenesis.

PMID- 20130063
TI  - Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus
      does not result in enhanced virulence or transmission.
AB  - In the first 6 months of the H1N1 swine-origin influenza virus (S-OIV) pandemic,
      the vast majority of infections were relatively mild. It has been postulated that
      mutations in the viral genome could result in more virulent viruses, leading to a
      more severe pandemic. Mutations E627K and D701N in the PB2 protein have
      previously been identified as determinants of avian and pandemic influenza virus
      virulence in mammals. These mutations were absent in S-OIVs detected early in the
      2009 pandemic. Here, using reverse genetics, mutations E627K, D701N, and E677G
      were introduced into the prototype S-OIV A/Netherlands/602/2009, and their
      effects on virus replication, virulence, and transmission were investigated.
      Mutations E627K and D701N caused increased reporter gene expression driven by the
      S-OIV polymerase complex. None of the three mutations affected virus replication
      in vitro. The mutations had no major impact on virus replication in the
      respiratory tracts of mice and ferrets or on pathogenesis. All three mutant
      viruses were transmitted via aerosols or respiratory droplets in ferrets. Thus,
      the impact of key known virulence markers in PB2 in the context of current S-OIVs
      was surprisingly small. This study does not exclude the possibility of emergence
      of S-OIVs with other virulence-associated mutations in the future. We conclude
      that surveillance studies aimed at detecting S-OIVs with increased virulence or
      transmission should not rely solely on virulence markers identified in the past
      but should include detailed characterization of virus phenotypes, guided by
      genetic signatures of viruses detected in severe cases of disease in humans.

PMID- 20130064
TI  - Interleukin 18 coexpression during respiratory syncytial virus infection results
      in enhanced disease mediated by natural killer cells.
AB  - Respiratory syncytial virus (RSV) causes bronchiolitis, the main cause of
      infantile hospitalization. Immunity against reinfection is poor, and there is
      great interest in boosting vaccine responses using live vectors expressing host
      cytokines. We therefore constructed a recombinant RSV expressing murine
      interleukin 18 (RSV/IL-18), a cytokine capable of inducing strong antiviral
      immune responses. In vitro RSV/IL-18 replicated at wild-type levels and produced
      soluble IL-18. In naive BALB/c mice, RSV/IL-18 infection significantly increased
      both IL-18 mRNA and protein and attenuated the peak viral load 3-fold. Despite a
      reduced viral load, RSV/IL-18 infection caused a biphasic weight loss at days 2
      and 6 postinfection that was not seen in wild-type infection. Day 2 disease was
      associated with enhanced pulmonary natural killer (NK) cell numbers and activity
      and was prevented by NK cell depletion during infection; day 6 disease was
      correlated with CD8 T-cell recruitment and was enhanced by NK cell depletion. IL
      18 expression during priming also enhanced RSV-specific antibody responses and T
      cell responses on secondary RSV infection. Therefore, while IL-18 boosted
      antiviral immunity and reduced the viral load, its coexpression worsened disease.
      This is the first recombinant RSV with this property, and these are the first
      studies to demonstrate that NK cells can induce pathology during pulmonary viral
      infections.

PMID- 20130065
TI  - Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated
      antiviral response.
AB  - The rabies virus Ni-CE strain causes nonlethal infection in adult mice after
      intracerebral inoculation, whereas the parental Nishigahara (Ni) strain kills
      mice. We previously reported that the chimeric CE(NiN) strain with the N gene
      from the Ni strain in the genetic background of the Ni-CE strain kills adult
      mice, indicating that the N gene is related to the different pathogenicities of
      Ni and Ni-CE strains. In the present study, to obtain an insight into the
      mechanism by which the N gene determines viral pathogenicity, we compared the
      effects of Ni, Ni-CE, and CE(NiN) infections on host gene expressions using a
      human neuroblastoma cell line. Microarray analysis of these infected cells
      revealed that the expression levels of particular genes in Ni- and CE(NiN)
      infected cells, including beta interferon (IFN-beta) and chemokine genes (i.e.,
      CXCL10 and CCL5) were lower than those in Ni-CE-infected cells. We also
      demonstrated that Ni-CE infection activated the interferon regulatory factor 3
      (IRF-3)-dependent IFN-beta promoter and induced IRF-3 nuclear translocation more
      efficiently than did Ni or CE(NiN) infection. Furthermore, we showed that Ni-CE
      infection, but not Ni or CE(NiN) infection, strongly activates the IRF-3 pathway
      through activation of RIG-I, which is known as a cellular sensor of virus
      infection. These findings indicate that the N protein of rabies virus (Ni strain)
      has a function to evade the activation of RIG-I. To our knowledge, this is the
      first report that the Mononegavirales N protein functions to evade induction of
      host IFN and chemokines.

PMID- 20130067
TI  - Exploring plant transcriptomes using ultra high-throughput sequencing.
AB  - Ultra high-throughput sequencing (UHTS) technologies offer the potential to
      interrogate transcriptomes in detail that has traditionally been restricted to
      single gene surveys. For instance, it is now possible to globally define
      transcription start sites, polyadenylation signals, alternative splice sites and
      generate quantitative data on gene transcript accumulation in single tissues or
      cell types. These technologies are thus paving the way for whole genome
      transcriptomics and will undoubtedly lead to novel insights into plant
      development and biotic and abiotic stress responses. However, several challenges
      exist to making this technology broadly accessible to the plant research
      community. These include the current need for a computationally intensive
      analysis of data sets, a lack of standardized alignment and formatting procedures
      and a relatively small number of analytical software packages to interpret UHTS
      outputs. In this review we summarize recent findings from UHTS and discuss
      potential opportunities and challenges for broad adoption of these technologies
      in the plant science community.

PMID- 20130066
TI  - A chimeric alphavirus replicon particle vaccine expressing the hemagglutinin and
      fusion proteins protects juvenile and infant rhesus macaques from measles.
AB  - Measles remains a major cause of child mortality, in part due to an inability to
      vaccinate young infants with the current live attenuated virus vaccine (LAV). To
      explore new approaches to infant vaccination, chimeric Venezuelan equine
      encephalitis/Sindbis virus (VEE/SIN) replicon particles were used to express the
      hemagglutinin (H) and fusion (F) proteins of measles virus (MV). Juvenile rhesus
      macaques vaccinated intradermally with a single dose of VEE/SIN expressing H or H
      and F proteins (VEE/SIN-H or VEE/SIN-H+F, respectively) developed high titers of
      MV-specific neutralizing antibody and gamma-interferon (IFN-gamma)-producing T
      cells. Infant macaques vaccinated with two doses of VEE/SIN-H+F also developed
      neutralizing antibody and IFN-gamma-producing T cells. Control animals were
      vaccinated with LAV or with a formalin-inactivated measles vaccine (FIMV).
      Neutralizing antibody remained above the protective level for more than 1 year
      after vaccination with VEE/SIN-H, VEE/SIN-H+F, or LAV. When challenged with wild
      type MV 12 to 17 months after vaccination, all vaccinated juvenile and infant
      monkeys vaccinated with VEE/SIN-H, VEE/SIN-H+F, and LAV were protected from rash
      and viremia, while FIMV-vaccinated monkeys were not. Antibody was boosted by
      challenge in all groups. T-cell responses to challenge were biphasic, with peaks
      at 7 to 25 days and at 90 to 110 days in all groups, except for the LAV group.
      Recrudescent T-cell activity coincided with the presence of MV RNA in peripheral
      blood mononuclear cells. We conclude that VEE/SIN expressing H or H and F induces
      durable immune responses that protect from measles and offers a promising new
      approach for measles vaccination. The viral and immunological factors associated
      with long-term control of MV replication require further investigation.

PMID- 20130068
TI  - Birth weight in relation to sex steroid status and body composition in young
      healthy male siblings.
AB  - CONTEXT: Sex steroid concentrations have a strong genetic determination, but
      environmental factors and body composition play an important role. From studies
      in children with intrauterine growth restriction, low birth weight has been
      associated with altered gonadotropin concentrations. OBJECTIVE: We aim to
      investigate sex steroid concentrations in healthy young brothers in relation to
      birth weight (normal gestational age), body composition, and parental steroid
      concentrations. DESIGN AND SETTING: We conducted a cross-sectional, population
      based sibling pair study with inclusion of parental data. PARTICIPANTS: A total
      of 677 men (25-45 yr old) were included in this study, with 296 independent pairs
      of brothers and 122 fathers. MAIN OUTCOMES: We measured testosterone, estradiol,
      leptin, adiponectin, IGF-I (immunoassays), and free steroid hormones (calculated)
      in relation to birth weight and changes in body composition (dual-energy x-ray
      absorptiometry). RESULTS: Birth weight was associated with serum testosterone (P
      = 0.0004) and SHBG (P = 0.0001), independent from weight, age, or fat mass,
      whereas no association with (free) estradiol, LH, or FSH was found. Paternal
      testosterone (P = 0.02), estradiol (P = 0.04), and SHBG (P = 0.0004) were
      associated with the respective sex steroid concentrations in the brothers. Weight
      increase (population rank) during life, was associated with lower testosterone (
      15%; P < 0.001), independent from current weight and with higher free estradiol
      concentrations (+8%; P = 0.002), whereas weight decrease was associated with
      higher testosterone (+13%; P < 0.001). CONCLUSION: Birth weight and paternal
      steroid concentrations are associated with testosterone concentrations,
      independent from adult weight. These findings support the concept of in utero
      programming across the range of birth weight.

PMID- 20130069
TI  - Skeletal effects of interventions in mild primary hyperparathyroidism: a meta
      analysis.
AB  - CONTEXT: Uncertainty exists as to the optimal management and monitoring of the
      skeletal consequences of mild primary hyperparathyroidism (PHPT). OBJECTIVE: The
      aim of this study was to determine the effects of surgical treatment, medical
      treatment and no treatment on bone mineral density (BMD) in mild PHPT. DATA
      SOURCES: Our sources were Medline, EMBASE, and Cochrane CENTRAL prior to January
      2009, and abstracts from meetings of international bone and mineral societies
      from 1987-2008. STUDY SELECTION: Eligible studies were of at least 1-yr duration
      and included more than 10 participants with mild PHPT (serum calcium < 12 mg/dl)
      who had BMD measured by dual-energy x-ray absorptiometry while being observed
      without intervention, or treated with antiresorptive therapy or surgery. Primary
      analysis was of studies of up to 2-yr duration. Secondary analysis was of studies
      with follow-up beyond 2 yr. DATA EXTRACTION: Data were extracted from the text of
      the retrieved articles or conference abstracts. DATA SYNTHESIS: Increases in BMD
      in response to surgical intervention were comparable to those induced by
      antiresorptive therapies. Significant bone loss was observed in untreated
      subjects, but the rates of loss ranged from 0.6-1.0%/yr. Analysis of studies
      reporting data beyond 2 yr of follow-up demonstrated stable increases in BMD
      after surgery and stable BMD or slow loss (0.1-0.3%/yr) in untreated PHPT.
      CONCLUSIONS: Surgical treatment and antiresorptive therapies increase BMD in mild
      PHPT to a similar degree, and each represents a reasonable option in a patient
      with mild PHPT and low BMD. Rapid bone loss does not occur in untreated mild
      PHPT, such that monitoring of BMD less frequently than every 1-2 yr is reasonable
      in individuals for whom intervention is not immediately required.

PMID- 20130070
TI  - Use of organic nitrates and the risk of hip fracture: a population-based case
      control study.
AB  - CONTEXT: Use of organic nitrates has been associated with increased bone mineral
      density. Moreover, a large Danish case-control study reported a decreased
      fracture risk. However, the association with duration of nitrate use, dose
      frequency, and impact of discontinuation has not been extensively studied.
      OBJECTIVE: Our objective was to evaluate the association between organic nitrates
      and hip fracture risk. METHODS: A case-control study was conducted using the
      Dutch PHARMO Record Linkage System (1991-2002, n = 6,763 hip fracture cases and
      26,341 controls). Cases had their first admission for hip fracture, whereas
      controls had not sustained any fracture after enrollment. Current users of
      organic nitrates were patients who had received a prescription within 90 d before
      the index date. The analyses were adjusted for disease and drug history. RESULTS:
      Current use of nitrates was not associated with a decreased risk of hip fracture
      [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83-1.04].
      Those who used as-needed medication only had a lower risk of hip fracture
      (adjusted OR = 0.83; 95% CI = 0.63-1.08) compared with users of maintenance
      medication only (adjusted OR = 1.17; 95% CI = 0.97-1.40). No association was
      found between duration of nitrate use and fracture risk. CONCLUSIONS: Our overall
      analyses showed that risk of a hip fracture was significantly lower among users
      of as-needed organic nitrates, when compared with users of maintenance
      medication. Our analyses of hip fracture risks with duration of use did not
      further support a beneficial effect of organic nitrates on hip fracture, although
      residual confounding may have masked beneficial effects.

PMID- 20130071
TI  - Mutations of the metabolic genes IDH1, IDH2, and SDHAF2 are not major
      determinants of the pseudohypoxic phenotype of sporadic pheochromocytomas and
      paragangliomas.
AB  - CONTEXT: Pheochromocytomas and paragangliomas are genetically heterogeneous
      tumors of neural crest origin. Approximately half of these tumors activate a
      pseudohypoxic transcription response, which is due in a minority of the cases to
      germline mutations of the VHL gene or the genes encoding subunits of the
      metabolic enzyme succinate dehydrogenase (SDH), SDHB, SDHC, or SDHD. However, the
      genetic basis of the hypoxic-like profile of the remaining tumors is
      undetermined. Mutations in genes involved in the energy metabolism, isocitrate
      dehydrogenase 1 (IDH1) and -2 (IDH2) and SDHAF2, a component of SDH, can mimic a
      pseudohypoxic state. DESIGN: We examined the sequence spanning the mutation
      susceptible codons 132 of IDH1 and 172 of IDH2, and the entire coding region of
      SDHAF2, in 104 pheochromocytomas and paragangliomas, including tumors with a
      pseudohypoxic expression profile. RESULTS: We did not find mutations in IDH1,
      IDH2, or SDHAF2 in any of the tumors in this cohort. CONCLUSION: Conserved
      residues of IDH1 and IDH2 or the SDHAF2 gene are not frequently mutated in
      pheochromocytomas and paragangliomas. The molecular basis for activation of a
      hypoxic response in the majority of tumors without VHL or SDH mutations remains
      to be defined.

PMID- 20130072
TI  - Elevated fasting plasma cortisol is associated with ischemic heart disease and
      its risk factors in people with type 2 diabetes: the Edinburgh type 2 diabetes
      study.
AB  - CONTEXT: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may
      underlie the metabolic syndrome, but whether circulating cortisol levels predict
      cardiovascular end points is less clear. People with type 2 diabetes are at
      increased cardiovascular disease risk and thus are suitable to study associations
      of plasma cortisol with cardiovascular risk. OBJECTIVE: We aimed to assess
      whether altered HPA axis activity was associated with features of the metabolic
      syndrome and ischemic heart disease in people with type 2 diabetes. DESIGN AND
      SETTING: We conducted a cross-sectional cohort study in the general community,
      including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the
      Edinburgh Type 2 Diabetes Study). INTERVENTION: We measured fasting morning
      plasma cortisol. MAIN OUTCOME MEASUREMENT: Associations between cortisol levels,
      features of the metabolic syndrome, obesity, and ischemic heart disease were
      determined. RESULTS: Elevated plasma cortisol levels were associated with raised
      fasting glucose and total cholesterol levels (P < 0.001). These findings remained
      significant after adjustment for potential confounding factors (P < 0.001).
      Elevated cortisol levels were associated with prevalent ischemic heart disease
      (>800 vs. <600 nmol/liter; odds ratio, 1.58; P = 0.02). This association remained
      significant after adjustment for duration and control of diabetes and other
      cardiovascular risk factors (P = 0.03). CONCLUSIONS: The previously described
      associations between HPA axis activation and features of the metabolic syndrome
      are present among people with type 2 diabetes. Elevated plasma cortisol is also
      associated with a greater prevalence of ischemic heart disease, independent of
      conventional risk factors. Understanding the role of cortisol in the pathogenesis
      of ischemic heart disease merits further exploration.

PMID- 20130073
TI  - Impact of proto-oncogene mutation detection in cytological specimens from thyroid
      nodules improves the diagnostic accuracy of cytology.
AB  - CONTEXT: Fine-needle aspiration cytology (FNAC) is the gold standard for the
      differential diagnosis of thyroid nodules but has the limitation of inadequate
      sampling or indeterminate lesions. OBJECTIVE: We aimed to verify whether search
      of thyroid cancer-associated protooncogene mutations in cytological samples may
      improve the diagnostic accuracy of FNAC. STUDY DESIGN: One hundred seventy-four
      consecutive patients undergoing thyroid surgery were submitted to FNAC (on 235
      thyroid nodules) that was used for cytology and molecular analysis of BRAF, RAS,
      RET, TRK, and PPRgamma mutations. At surgery these nodules were sampled to
      perform the same molecular testing. RESULTS: Mutations were found in 67 of 235
      (28.5%) cytological samples. Of the 67 mutated samples, 23 (34.3%) were mutated
      by RAS, 33 (49.3%) by BRAF, and 11 (16.4%) by RET/PTC. In 88.2% of the cases, the
      mutation was confirmed in tissue sample. The presence of mutations at cytology
      was associated with cancer 91.1% of the times and follicular adenoma 8.9% of the
      time. BRAF or RET/PTC mutations were always associated with cancer, whereas RAS
      mutations were mainly associated with cancer (74%) but also follicular adenoma
      (26%). The diagnostic performance of molecular analysis was superior to that of
      traditional cytology, with better sensitivity and specificity, and the
      combination of the two techniques further contributed to improve the total
      accuracy (93.2%), compared with molecular analysis (90.2%) or traditional
      cytology (83.0%). CONCLUSIONS: Our findings demonstrate that molecular analysis
      of cytological specimens is feasible and that its results in combination with
      cytology improves the diagnostic performance of traditional cytology.

PMID- 20130074
TI  - Universal screening versus case finding for detection and treatment of thyroid
      hormonal dysfunction during pregnancy.
AB  - CONTEXT: Thyroid disease during pregnancy has been associated with multiple
      adverse outcomes. Whether all women should be screened for thyroid disease during
      pregnancy is controversial. OBJECTIVE: The objective of the study was to
      determine whether treatment of thyroid disease during pregnancy decreases the
      incidence of adverse outcomes and compare the ability of universal screening vs.
      case finding in detecting thyroid dysfunction. DESIGN: Women in the first
      trimester were randomly assigned to the universal screening group or case-finding
      group. Women in both groups were stratified as high risk or low risk based on
      risk factors for thyroid disease. All women in the universal screening group, and
      high-risk women in the case-finding group, were immediately tested for free T(4),
      TSH, and thyroid peroxidase antibody. Low-risk women in the case-finding group
      had their sera tested postpartum. SETTING: The study was conducted at two
      ambulatory clinics of community hospitals in southern Italy. PATIENTS: A total of
      4562 women were randomly assigned to the universal screening or case-finding
      group. INTERVENTION: Intervention included levothyroxine in women with a TSH
      above 2.5 mIU/liter in TPO antibody-positive women and antithyroid medication in
      women with a undetectable TSH and elevated free T(4). MAIN OUTCOME MEASURE: Total
      number of adverse obstetrical and neonatal outcomes was measured. RESULTS: No
      significant differences were seen in adverse outcomes between the case-finding
      and universal screening groups. Adverse outcomes were less likely to occur among
      low-risk women in the screening group than those in the case-finding group.
      CONCLUSIONS: Universal screening compared with case finding did not result in a
      decrease in adverse outcomes. Treatment of hypothyroidism or hyperthyroidism
      identified by screening a low-risk group was associated with a lower rate of
      adverse outcomes.

PMID- 20130075
TI  - The predictive value of different measures of obesity for incident cardiovascular
      events and mortality.
AB  - CONTEXT: To date, it is unclear which measure of obesity is the most appropriate
      for risk stratification. OBJECTIVE: The aim of the study was to compare the
      associations of various measures of obesity with incident cardiovascular events
      and mortality. DESIGN AND SETTING: We analyzed two German cohort studies, the
      DETECT study and SHIP, including primary care and general population.
      PARTICIPANTS: A total of 6355 (mean follow-up, 3.3 yr) and 4297 (mean follow-up,
      8.5 yr) individuals participated in DETECT and SHIP, respectively. INTERVENTIONS:
      We measured body mass index (BMI), waist circumference (WC), waist-to-height
      ratio (WHtR), and waist-to-hip ratio (WHR) and assessed cardiovascular and all
      cause mortality and the composite endpoint of incident stroke, myocardial
      infarction, or cardiovascular death. RESULTS: In both studies, we found a
      positive association of the composite endpoint with WHtR but not with BMI. There
      was no heterogeneity among studies. The relative risks in the highest versus the
      lowest sex- and age-specific quartile of WHtR, WC, WHR, and BMI after adjustment
      for multiple confounders were as follows in the pooled data: cardiovascular
      mortality, 2.75 (95% confidence interval, 1.31-5.77), 1.74 (0.84-3.6), 1.71 (0.91
      3.22), and 0.74 (0.35-1.57), respectively; all-cause mortality, 1.86 (1.25-2.76),
      1.62 (1.22-2.38), 1.36 (0.93-1.69), and 0.77 (0.53-1.13), respectively; and
      composite endpoint, 2.16 (1.39-3.35), 1.59 (1.04-2.44), 1.49 (1.07-2.07), and
      0.57 (0.37-0.89), respectively. Separate analyses of sex and age groups yielded
      comparable results. Receiver operating characteristics analysis yielded the
      highest areas under the curve for WHtR for predicting these endpoints.
      CONCLUSIONS: WHtR represents the best predictor of cardiovascular risk and
      mortality, followed by WC and WHR. Our results discourage the use of the BMI.

PMID- 20130076
TI  - LMNA mutations, skeletal muscle lipid metabolism, and insulin resistance.
AB  - CONTEXT: Type 2 familial partial lipodystrophy (FPLD) is an autosomal-dominant
      lamin A/C-related disease associated with exercise intolerance, muscular pain,
      and insulin resistance. The symptoms may all be explained by defective
      metabolism; however, metabolism at the tissue level has not been investigated.
      OBJECTIVE: We hypothesized that in FPLD, insulin resistance and impaired aerobic
      exercise capacity are explained by a common underlying mechanism, presumably a
      muscular metabolic defect. PATIENTS AND METHODS: Carbohydrate and lipid
      metabolism was studied on 10 FPLD patients, one patient with limb-girdle muscular
      dystrophy (LGMD1B, a different lamin A/C disease), and 10 healthy control
      subjects before and during an oral glucose tolerance test by indirect calorimetry
      and im microdialysis. Muscle biopsies were taken for in vitro studies. RESULTS:
      We observed marked increased skeletal muscle fatty acid beta-oxidation rate in
      vitro and in vivo, even after glucose ingestion in FPLD patients. However, fatty
      acid oxidation was largely incomplete and accompanied by increased ketogenesis.
      The lipid oxidation abnormality was associated with impaired glucose disposition
      through reduction in glucose oxidation, rather than decreased cellular glucose
      uptake. A microarray showed down-regulation of complex I respiratory chain,
      glycolysis, and nuclear transport genes. Although not overtly insulin resistant,
      the LGMD1B patient showed similar metabolic derangements as the FPLD patients.
      CONCLUSIONS: Our study suggests imbalance between lipid oxidation and oxidative
      glucose metabolism in FPLD and LGMD1B patients. The observation suggests an
      intrinsic defect in skeletal muscle metabolism due to lamin A/C dysfunction. The
      metabolic FPLD phenotype likely results from this intrinsic defect combined with
      lipodystrophic "lipid pressure" due to decreased adipose tissue lipid storage
      capacity.

PMID- 20130077
TI  - Aldosterone production and insulin resistance in healthy adults.
AB  - CONTEXT: Aldosterone production is associated with insulin resistance in obese
      and hypertensive subjects. However, its effect on insulin sensitivity in healthy
      subjects is not clear. OBJECTIVE: The objective of this study was to test the
      hypothesis that increased aldosterone production is associated with lower insulin
      sensitivity in healthy subjects. DESIGN: This is an analysis of data previously
      collected during studies conducted as part of the International Hypertensive
      Pathotype Consortium. PARTICIPANTS AND INTERVENTIONS: Eighty-four subjects free
      of any medical or psychiatric illness were included in this study. They were
      studied after 7 d of a standardized high-sodium diet confirmed by 24-h urine
      sodium above 200 mEq. Insulin sensitivity index (ISI) was calculated after a 75-g
      oral glucose load with glucose and insulin measurements at 0, 30, 60, and 120
      min. Serum aldosterone levels were measured after 45 min of angiotensin II (3
      ng/kg/min) infusion. RESULTS: There were significant negative correlations
      between ISI and age, body mass index (BMI), diastolic blood pressure, and
      angiotensin II-stimulated aldosterone level (P < 0.01). On multivariate
      regression analysis, stimulated aldosterone level was an independent predictor of
      ISI after adjusting for age, BMI, and diastolic blood pressure. Stimulated
      aldosterone level predicted 8% of the variance in ISI (P = 0.003) with age, BMI,
      and diastolic blood pressure together predicting 23% of the variance in ISI.
      Thus, the final regression model predicted 31% of the variance in ISI (P <
      0.0001). CONCLUSIONS: Aldosterone production is associated with insulin
      resistance in normotensive healthy subjects independent of traditional risk
      factors.

PMID- 20130078
TI  - Clinical Review#: Potential cardiac valve effects of dopamine agonists in
      hyperprolactinemia.
AB  - CONTEXT: An association has been demonstrated between valvular heart disease and
      dopamine agonist use in patients treated for Parkinson's disease. Following these
      reports, concern has been raised among endocrinologists about the safety of long
      term treatment with dopamine agonists in hyperprolactinemic patients. The article
      will summarize all currently published research regarding the possible risk of
      valvulopathy in hyperprolactinemic patients on dopamine agonists and provide
      guidance based on current findings. EVIDENCE ACQUISITION: The major source of
      data acquisition included PubMed search strategies. PubMed was searched for
      publications containing the terms "valve," "valvular," or "valvulopathy," and one
      of the terms "dopamine agonists," "cabergoline," "bromocriptine," "pergolide,"
      "prolactin," "prolactinoma," or "hyperprolactinemia." All publications from 1950
      to August, 2008, were screened for use in this review. EVIDENCE SYNTHESIS: The
      majority of studies showed no risk of valvular regurgitation associated with
      cabergoline. However, an increased risk of mild to moderate regurgitation,
      usually at the tricuspid valve, was reported in a few studies. Only one study
      suggested a relationship with the mean cumulative dose of cabergoline.
      CONCLUSIONS: Although most reports do not show an association between use of
      dopamine agonists and valvulopathy, caution must be exercised, especially in
      patients requiring long-term, high-dose medication regimens. Clinicians should
      recommend the lowest possible doses of dopamine agonists and address the question
      of echocardiographic monitoring on an individual basis.

PMID- 20130079
TI  - Guidance for substantiating the evidence for beneficial effects of probiotics:
      prevention and management of allergic diseases by probiotics.
AB  - Allergy is a hypersensitivity reaction mediated by specific antibody-mediated or
      cell-mediated immunologic mechanisms and clinically manifested as atopic eczema,
      allergic rhinoconjunctivitis, or asthma. During the recent decades there has been
      an increase in allergy prevalence, which is attributed to changes in
      environmental factors. The so-called "hygiene hypothesis" suggests that a lack of
      exposure to microbial stimulus early in childhood is a major factor involved in
      this trend. This provides a rationale for using probiotics to modify the gut
      microbiota and thereby shaping the immune response of the host, especially in
      infancy. Most success has been obtained in primary prevention of atopic eczema. A
      limited number of studies also provided evidence for a beneficial effect of
      different probiotics in the management of allergic diseases (atopic eczema,
      allergic rhinitis). However, choice of probiotic strains as well as timing of the
      intervention are important variables. The exact in vivo mechanism of probiotics
      in shaping the immune response still needs to be determined. Future studies
      should use uniform criteria for diagnosis and symptom scoring of atopic diseases
      and may identify the genes predisposing to allergic disease. There is encouraging
      evidence that specific probiotics can become valuable tools in the prevention and
      management of allergic diseases.

PMID- 20130080
TI  - Guidance for substantiating the evidence for beneficial effects of probiotics:
      current status and recommendations for future research.
AB  - Probiotic bacteria are live microorganisms that, when administered in adequate
      amounts, confer a health benefit on the host. There is a growing interest in
      probiotics within the scientific community, with consumers, and in the food
      industry. The interactions between the gut and intestinal microbiota and between
      resident and transient microbiota define a new arena in physiology, an
      understanding of which would shed light on the "cross-talk" between humans and
      microbes. The different beneficial effects of specific probiotic strains may be
      translated into different health claims. However, there is a need for
      comprehensive and harmonized guidelines on the assessment of the characteristics
      and efficacy of probiotics and of foods containing them. An international expert
      group of ILSI has evaluated the published evidence of the functionality of
      different probiotics in 4 areas of (human) application: 1) metabolism, 2) chronic
      intestinal inflammatory and functional disorders, 3) infections, and 4) allergy.
      Based on the existing evidence, concrete examples of demonstration of benefits
      and gaps are listed, and guidelines and recommendations are defined that should
      help design the next generation of probiotic studies.

PMID- 20130081
TI  - Manganese-induced trafficking and turnover of the cis-Golgi glycoprotein GPP130.
AB  - Manganese is an essential element that is also neurotoxic at elevated exposure.
      However, mechanisms regulating Mn homeostasis in mammalian cells are largely
      unknown. Because increases in cytosolic Mn induce rapid changes in the
      localization of proteins involved in regulating intracellular Mn concentrations
      in yeast, we were intrigued to discover that low concentrations of extracellular
      Mn induced rapid redistribution of the mammalian cis-Golgi glycoprotein Golgi
      phosphoprotein of 130 kDa (GPP130) to multivesicular bodies. GPP130 was
      subsequently degraded in lysosomes. The Mn-induced trafficking of GPP130 occurred
      from the Golgi via a Rab-7-dependent pathway and did not require its transit
      through the plasma membrane or early endosomes. Although the cytoplasmic domain
      of GPP130 was dispensable for its ability to respond to Mn, its lumenal stem
      domain was required and it had to be targeted to the cis-Golgi for the Mn
      response to occur. Remarkably, the stem domain was sufficient to confer Mn
      sensitivity to another cis-Golgi protein. Our results identify the stem domain of
      GPP130 as a novel Mn sensor in the Golgi lumen of mammalian cells.

PMID- 20130082
TI  - PICH and cotargeted Plk1 coordinately maintain prometaphase chromosome arm
      architecture.
AB  - To maintain genomic stability, chromosome architecture needs to be tightly
      regulated as chromosomes undergo condensation during prophase and separation
      during anaphase, but the mechanisms remain poorly understood. Here, we show that
      the Plk1-binding protein PICH and Plk1 kinase coordinately maintain chromosome
      architecture during prometaphase. PICH knockdown results in a loss of Plk1 from
      the chromosome arm and an increase in highly disorganized "wavy" chromosomes that
      exhibit an "open" or "X-shaped" configuration, consistent with a loss of
      chromosome arm cohesion. Such chromosome disorganization occurs with essentially
      no change in the localization of condensin or cohesin on chromosomes.
      Interestingly, the chromosome disorganization could be prevented by treatment
      with a topoisomerase II inhibitor ICRF-193, suggesting that the PICH-Plk1 complex
      normally maintains chromosome architecture in a manner that involves
      topoisomerase II activity. PICH knockdown does not affect initial chromosome
      compaction at prophase but causes anaphase DNA bridge formation and failed
      abscission. Our studies suggest that the PICH-Plk1 complex plays a critical role
      in maintaining prometaphase chromosome architecture.

PMID- 20130083
TI  - Evasion of endoplasmic reticulum surveillance makes Wsc1p an obligate substrate
      of Golgi quality control.
AB  - In the endoplasmic reticulum (ER), most newly synthesized proteins are retained
      by quality control mechanisms until folded. Misfolded molecules are sorted to ER
      associated degradation (ERAD) pathways for disposal. Reports of mutant proteins
      degraded in the vacuole/lysosome suggested an independent Golgi-based mechanism
      also at work. Although little is understood of the post-ER pathway, the growing
      number of variants using it suggests a major role in quality control. Why
      seemingly redundant mechanisms in sequential compartments are needed is unclear.
      To understand their physiological relationship, the identification of endogenous
      pathway-specific substrates is a prerequisite. With ERAD substrates already well
      characterized, the discovery of Wsc1p as an obligate substrate of Golgi quality
      control enabled detailed cross-pathway analyses for the first time. By analyzing
      a panel of engineered substrates, the data show that the surveillance mode is
      determined by each polypeptide's intrinsic design. Although most secretory
      pathway proteins can display ERAD determinants when misfolded, the lack thereof
      shields Wsc1p from inspection by ER surveillance. Additionally, a powerful ER
      export signal mediates transport whether the luminal domain is folded or not. By
      evading ERAD through these passive and active mechanisms, Wsc1p is fully
      dependent on the post-ER system for its quality control.

PMID- 20130084
TI  - A guaninine nucleotide exchange factor is a component of the meiotic spindle pole
      body in Schizosaccharomyces pombe.
AB  - Spore morphogenesis in yeast is driven by the formation of membrane compartments
      that initiate growth at the spindle poles during meiosis II and grow to
      encapsulate daughter nuclei. Vesicle docking complexes, called meiosis II outer
      plaques (MOPs), form on each meiosis II spindle pole body (SPB) and serve as
      sites of membrane nucleation. How the MOP stimulates membrane assembly is not
      known. Here, we report that SpSpo13, a component of the MOP in
      Schizosaccharomyces pombe, shares homology with the guanine nucleotide exchange
      factor (GEF) domain of the Saccharomyces cerevisiae Sec2 protein. ScSec2 acts as
      a GEF for the small Rab GTPase ScSec4, which regulates vesicle trafficking from
      the late-Golgi to the plasma membrane. A chimeric protein in which the ScSec2-GEF
      domain is replaced with SpSpo13 is capable of supporting the growth of a
      sec2Delta mutant. SpSpo13 binds preferentially to the nucleotide-free form of
      ScSec4 and facilitates nucleotide exchange in vitro. In vivo, a Spspo13 mutant
      defective in GEF activity fails to support membrane assembly. In vitro
      specificity experiments suggest that SpYpt2 is the physiological substrate of
      SpSpo13. These results demonstrate that stimulation of Rab-GTPase activity is a
      property of the S. pombe MOP essential for the initiation of membrane formation.

PMID- 20130085
TI  - The Ero1alpha-PDI redox cycle regulates retro-translocation of cholera toxin.
AB  - Cholera toxin (CT) is transported from the plasma membrane of host cells to the
      endoplasmic reticulum (ER) where the catalytic CTA1 subunit retro-translocates to
      the cytosol to induce toxicity. Our previous analyses demonstrated that the ER
      oxidoreductase protein disulfide isomerase (PDI) acts as a redox-dependent
      chaperone to unfold CTA1, a reaction postulated to initiate toxin retro
      translocation. In its reduced state, PDI binds and unfolds CTA1; subsequent
      oxidation of PDI by Ero1alpha enables toxin release. Whether this in vitro model
      describes events in cells that control CTA1 retro-translocation is unknown. Here
      we show that down-regulation of Ero1alpha decreases retro-translocation of CTA1
      by increasing reduced PDI and blocking efficient toxin release. Overexpression of
      Ero1alpha also attenuates CTA1 retro-translocation, an effect due to increased
      PDI oxidation, which prevents PDI from engaging the toxin effectively.
      Interestingly, Ero1alpha down-regulation increases interaction between PDI and
      Derlin-1, an ER membrane protein that is a component of the retro-translocation
      complex. These findings demonstrate that an appropriate Ero1alpha-PDI ratio is
      critical for regulating the binding-release cycle of CTA1 by PDI during retro
      translocation, and implicate PDI's redox state in targeting it to the retro
      translocon.

PMID- 20130086
TI  - The Na+/H+ exchanger NHE6 in the endosomal recycling system is involved in the
      development of apical bile canalicular surface domains in HepG2 cells.
AB  - Polarized epithelial cells develop and maintain distinct apical and basolateral
      surface domains despite a continuous flux of membranes between these domains. The
      Na(+)/H(+)exchanger NHE6 localizes to endosomes but its function is unknown.
      Here, we demonstrate that polarized hepatoma HepG2 cells express an NHE6.1
      variant that localizes to recycling endosomes and colocalizes with transcytosing
      bulk membrane lipids. NHE6.1 knockdown or overexpression decreases or increases
      recycling endosome pH, respectively, and inhibits the maintenance of apical, bile
      canalicular plasma membranes and, concomitantly, apical lumens. NHE6.1 knockdown
      or overexpression has little effect on the de novo biogenesis of apical surface
      domains. NHE6.1 knockdown does not inhibit basolateral-to-apical transcytosis of
      bulk membrane lipids, but it does promote their progressive loss from the apical
      surface, leaving cells unable to efficiently retain bulk membrane and bile
      canalicular proteins at the apical surface. The data suggest that a limited range
      of endosome pH mediated by NHE6.1 is important for securing the polarized
      distribution of membrane lipids at the apical surface and maintenance of apical
      bile canaliculi in HepG2 cells and hence cell polarity. This study underscores
      the emerging role of the endosomal recycling system in apical surface development
      and identifies NHE6 as a novel regulatory protein in this process.

PMID- 20130087
TI  - Par-4: a new activator of myosin phosphatase.
AB  - Myosin phosphatase (MP) is a key regulator of myosin light chain (LC20)
      phosphorylation, a process essential for motility, apoptosis, and smooth muscle
      contractility. Although MP inhibition is well studied, little is known about MP
      activation. We have recently demonstrated that prostate apoptosis response (Par)
      4 modulates vascular smooth muscle contractility. Here, we test the hypothesis
      that Par-4 regulates MP activity directly. We show, by proximity ligation assays,
      surface plasmon resonance and coimmunoprecipitation, that Par-4 interacts with
      the targeting subunit of MP, MYPT1. Binding is mediated by the leucine zippers of
      MYPT1 and Par-4 and reduced by Par-4 phosphorylation. Overexpression of Par-4
      leads to increased phosphatase activity of immunoprecipitated MP, whereas small
      interfering RNA knockdown of endogenous Par-4 significantly decreases MP activity
      and increases MYPT1 phosphorylation. LC20 phosphorylation assays demonstrate that
      overexpression of Par-4 reduces LC20 phosphorylation. In contrast, a
      phosphorylation site mutant, but not wild-type Par-4, interferes with zipper
      interacting protein kinase (ZIPK)-mediated MP inhibition. We conclude from our
      results Par-4 operates through a "padlock" model in which binding of Par-4 to
      MYPT1 activates MP by blocking access to the inhibitory phosphorylation sites,
      and inhibitory phosphorylation of MYPT1 by ZIPK requires "unlocking" of Par-4 by
      phosphorylation and displacement of Par-4 from the MP complex.

PMID- 20130088
TI  - Indole-3-carbinol triggers aryl hydrocarbon receptor-dependent estrogen receptor
      (ER)alpha protein degradation in breast cancer cells disrupting an ERalpha-GATA3
      transcriptional cross-regulatory loop.
AB  - Estrogen receptor (ER)alpha is a critical target of therapeutic strategies to
      control the proliferation of hormone-dependent breast cancers. Preferred clinical
      options have significant adverse side effects that can lead to treatment
      resistance due to the persistence of active estrogen receptors. We have
      established the cellular mechanism by which indole-3-carbinol (I3C), a promising
      anticancer phytochemical from Brassica vegetables, ablates ERalpha expression,
      and we have uncovered a critical role for the GATA3 transcription factor in this
      indole-regulated cascade. I3C-dependent activation of the aryl hydrocarbon
      receptor (AhR) initiates Rbx-1 E3 ligase-mediated ubiquitination and proteasomal
      degradation of ERalpha protein. I3C inhibits endogenous binding of ERalpha with
      the 3'-enhancer region of GATA3 and disrupts endogenous GATA3 interactions with
      the ERalpha promoter, leading to a loss of GATA3 and ERalpha expression. Ectopic
      expression of GATA3 has no effect on I3C-induced ERalpha protein degradation but
      does prevent I3C inhibition of ERalpha promoter activity, demonstrating the
      importance of GATA3 in this I3C-triggered cascade. Our preclinical results
      implicate I3C as a novel anticancer agent in human cancers that coexpress
      ERalpha, GATA3, and AhR, a combination found in a large percentage of breast
      cancers but not in other critical ERalpha target tissues essential to patient
      health.

PMID- 20130089
TI  - Interdependence of the peroxisome-targeting receptors in Arabidopsis thaliana:
      PEX7 facilitates PEX5 accumulation and import of PTS1 cargo into peroxisomes.
AB  - Peroxisomes compartmentalize certain metabolic reactions critical to plant and
      animal development. The import of proteins from the cytosol into the organelle
      matrix depends on more than a dozen peroxin (PEX) proteins, with PEX5 and PEX7
      serving as receptors that shuttle proteins bearing one of two peroxisome
      targeting signals (PTSs) into the organelle. PEX5 is the PTS1 receptor; PEX7 is
      the PTS2 receptor. In plants and mammals, PEX7 depends on PEX5 binding to deliver
      PTS2 cargo into the peroxisome. In this study, we characterized a pex7 missense
      mutation, pex7-2, that disrupts both PEX7 cargo binding and PEX7-PEX5
      interactions in yeast, as well as PEX7 protein accumulation in plants. We
      examined localization of peroxisomally targeted green fluorescent protein
      derivatives in light-grown pex7 mutants and observed not only the expected
      defects in PTS2 protein import but also defects in PTS1 import. These PTS1 import
      defects were accompanied by reduced PEX5 accumulation in light-grown pex7
      seedlings. Our data suggest that PEX5 and PTS1 import depend on the PTS2 receptor
      PEX7 in Arabidopsis and that the environment may influence this dependence. These
      data advance our understanding of the biogenesis of these essential organelles
      and provide a possible rationale for the retention of the PTS2 pathway in some
      organisms.

PMID- 20130090
TI  - Syntaxin 6 and CAL mediate the degradation of the cystic fibrosis transmembrane
      conductance regulator.
AB  - The PDZ domain-containing protein CAL mediates lysosomal trafficking and
      degradation of CFTR. Here we demonstrate the involvement of a CAL-binding SNARE
      protein syntaxin 6 (STX6) in this process. Overexpression of STX6, which
      colocalizes and coimmunoprecipitates with CAL, dramatically reduces the steady
      state level and stability of CFTR. Conversely, overexpression of a STX6 dominant
      negative mutant increases CFTR. Silencing endogenous STX6 increases CFTR but has
      no effect on DeltaTRL-CFTR, which cannot bind to CAL. Silencing CAL eliminates
      the effect of STX6 on CFTR. Both results suggest a dependence of CAL on STX6
      function. Consistent with its Golgi localization, STX6 does not bind to ER
      localized DeltaF508-CFTR. Silencing STX6 has no effect on DeltaF508-CFTR
      expression. However, overexpression of STX6 coimmunoprecipitates with and reduces
      temperature-rescued DeltaF508-CFTR that escapes ER degradation. Conversely,
      silencing STX6 enhances the effect of low temperature in rescuing DeltaF508-CFTR.
      Finally, in human bronchial epithelial cells, silencing endogenous STX6 leads to
      increases in protein levels and Cl(-) currents of both wild-type and temperature
      rescued CFTR. We have identified STX6 as a new component of the CAL complex that
      regulates the abundance and function of CFTR at the post-ER level. Our results
      suggest a therapeutic role of STX6 in enhancing rescued DeltaF508-CFTR.

PMID- 20130091
TI  - Psychopathy, ADHD, and brain dysfunction as predictors of lifetime recidivism
      among sex offenders.
AB  - This study examines the best predictor of lifetime recidivism among Hare's
      psychopathy scores (PCL-R), attention deficit hyperactivity disorder (ADHD)
      diagnosis, and brain dysfunction measures in a sample of 1,695 adult male sexual,
      violent, and nonviolent offenders. Results indicated that most variables were
      associated with significantly more frequent recidivism. The best predictor of
      overall recidivism was the PCL-R, but more specifically, it was its items on
      criminal history that were associated with recidivism. Sexual offense recidivism
      was predicted by the presence of learning disorders; however, all measures were
      poor predictors. General recidivism was primarily associated with past criminal
      history and secondarily with learning disorders and ADHD. Results suggest that
      ADHD and brain dysfunction with criminal history measures are the best predictors
      for addressing the problem of criminal recidivism.

PMID- 20130092
TI  - Introduction. US Food and Drug Administration Nutrition Facts Panel.

PMID- 20130093
TI  - Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on
      neuromuscular function and tolerability in older adults with vitamin D
      insufficiency.
AB  - BACKGROUND: Vitamin D insufficiency, which is prevalent in older individuals, is
      associated with bone and muscle weakness and falls. OBJECTIVE: We examined the
      effects of a weekly dose of 8400 IU vitamin D(3) on postural stability, muscle
      strength, and safety. DESIGN: In this double-blind trial, subjects aged > or =70
      y with serum 25-hydroxyvitamin D [25(OH)D] concentrations < or =20 but > or =6
      ng/mL were randomly assigned to receive a weekly dose of 8400 IU vitamin D(3) (n
      = 114) or a placebo (n = 112). Mediolateral body sway with eyes open (assessed
      with the AccuSway(PLUS) platform; Advanced Medical Technology Inc, Watertown, MA)
      was the primary endpoint. Secondary endpoints included the short physical
      performance battery (SPPB) and serum 25(OH)D concentrations. An analysis of
      covariance model was used for treatment comparisons. Safety and tolerability were
      monitored. RESULTS: Serum 25(OH)D concentrations rose significantly (from 13.9 to
      26.2 ng/mL, P < 0.001) in patients treated with 8400 IU vitamin D(3) but not in
      patients treated with the placebo. After 16 wk, neither mediolateral sway nor
      SPPB differed significantly between treatment groups. However, in the post hoc
      analysis of patients subgrouped by baseline sway (> or = 0.46 compared with <0.46
      cm), treatment with 8400 IU vitamin D(3) significantly reduced sway compared with
      treatment with placebo (P = 0.047) in patients with elevated baseline sway but
      not in patients with normal baseline sway. Adverse experiences and incidences of
      hypercalcemia, hypercalciuria, and elevated creatinine were similar with both
      treatments. In patients treated with 8400 IU vitamin D(3), but not in placebo
      treated patients, parathyroid hormone decreased significantly. CONCLUSIONS:
      Weekly treatment with 8400 IU vitamin D(3) raised 25(OH)D concentrations in
      elderly, vitamin D-insufficient individuals. Treatment with 8400 IU vitamin D(3)
      did not reduce mediolateral sway significantly compared with treatment with
      placebo in this population, although in post hoc analysis, treatment with 8400 IU
      vitamin D(3) reduced sway in the subgroup of patients who had elevated sway at
      baseline. Weekly treatment with 8400 IU vitamin D(3) was well tolerated. This
      trial was registered at clinicaltrials.gov as NCT00242476.

PMID- 20130094
TI  - Docosahexaenoic acid supplementation increases prefrontal cortex activation
      during sustained attention in healthy boys: a placebo-controlled, dose-ranging,
      functional magnetic resonance imaging study.
AB  - BACKGROUND: Emerging evidence suggests that docosahexaenoic acid (DHA, 22:6n-3),
      the principal omega-3 (n-3) fatty acid in brain gray matter, positively regulates
      cortical metabolic function and cognitive development. However, the effects of
      DHA supplementation on functional cortical activity in human subjects are
      unknown. OBJECTIVE: The objective was to determine the effects of DHA
      supplementation on functional cortical activity during sustained attention in
      human subjects. DESIGN: Healthy boys aged 8-10 y (n = 33) were randomly assigned
      to receive placebo or 1 of 2 doses of DHA (400 or 1200 mg/d) for 8 wk. Relative
      changes in cortical activation patterns during sustained attention at baseline
      and endpoint were determined by functional magnetic resonance imaging. RESULTS:
      At 8 wk, erythrocyte membrane DHA composition increased significantly from
      baseline in subjects who received low-dose (by 47%) or high-dose (by 70%) DHA but
      not in those who received placebo (-11%). During sustained attention, both DHA
      dose groups had significantly greater changes from baseline in activation of the
      dorsolateral prefrontal cortex than did the placebo group, and the low-dose and
      high-dose DHA groups had greater decreases in the occipital cortex and cerebellar
      cortex, respectively. Relative to low-dose DHA, high-dose DHA resulted in greater
      decreases in activation of bilateral cerebellum. The erythrocyte DHA composition
      was positively correlated with dorsolateral prefrontal cortex activation and was
      inversely correlated with reaction time, at baseline and endpoint. CONCLUSION:
      Dietary DHA intake and associated elevations in erythrocyte DHA composition are
      associated with alterations in functional activity in cortical attention networks
      during sustained attention in healthy boys. This trial was registered at
      clinicaltrials.gov as NCT00662142.

PMID- 20130095
TI  - The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double
      masked, randomized controlled clinical trial of the maturation of infant visual
      acuity as a function of the dietary level of docosahexaenoic acid.
AB  - BACKGROUND: The range of human milk docosahexaenoic acid (DHA) concentrations
      worldwide is much broader than the range explored in randomized clinical trials
      to date. OBJECTIVE: The primary objective was to determine the effect of 4
      amounts of DHA supplementation on the visual acuity of formula-fed infants at 12
      mo of age. Secondary objectives were to evaluate visual acuity maturation, red
      blood cell fatty acids, tolerance, anthropometric measures, and adverse events.
      DESIGN: This double-masked, randomized trial was conducted at 2 sites (Dallas and
      Kansas City). Three hundred forty-three healthy, term, formula-fed infants were
      enrolled at 1-9 d of age and were randomly assigned to be fed 1 of the following
      4 infant formulas containing equivalent nutrient amounts, except for long-chain
      polyunsaturated fatty acids: control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96%
      DHA; DHA-supplemented formulas also provided 0.64% arachidonic acid. Visual
      acuity was measured by visual evoked potentials in 244 infants who completed the
      12-mo primary outcome examination. RESULTS: Infants fed control formula had
      significantly poorer visual evoked potential visual acuity at 12 mo of age than
      did infants who received any of the DHA-supplemented formulas (P < 0.001). There
      were no significant differences in visual evoked potential visual acuity between
      the 3 amounts of DHA supplementation for either site at any age tested.
      CONCLUSIONS: DHA supplementation of infant formula at 0.32% of total fatty acids
      improves visual acuity. Higher amounts of DHA supplementation were not associated
      with additional improvement of visual acuity. This trial was registered at
      clinicaltrials.gov as NCT00753818.

PMID- 20130096
TI  - Nutrient profiling systems: are science and the consumer connected?
AB  - The other articles in this supplement to the Journal presented the science behind
      4 nutrient profiling systems currently available in the US marketplace that cross
      manufacturers and apply to multiple food categories and have considered their
      value as tools to promote positive behavior change in American consumers. This
      article discusses these nutrient profiling systems in terms of the consumer's
      understanding of science, familiarity with label messaging, and potential to
      facilitate healthy food decisions.

PMID- 20130097
TI  - Diet-heart: a problematic revisit.

PMID- 20130098
TI  - Updated systematic review and meta-analysis of the effects of n-3 long-chain
      polyunsaturated fatty acids on depressed mood.
AB  - BACKGROUND: The debate over a role for n-3 long-chain polyunsaturated fatty acids
      (n-3 PUFAs) in depressed mood continues. OBJECTIVE: The objective was to update a
      previous systematic review and meta-analysis of published randomized controlled
      trials investigating the effects of n-3 PUFAs on depressed mood and to explore
      potential sources of heterogeneity. DESIGN: Eight databases were searched for
      trials that randomly assigned participants to receive n-3 PUFAs/fish, measured
      depressed mood, used human participants, and included a comparison group up to
      April 2009. RESULTS: Thirty-five randomized controlled trials were identified; 17
      were not included in the previous review. The pooled standardized difference in
      mean outcome of the 29 trials that provided data to allow pooling (fixed-effects
      model) was 0.10 SD (95% CI: 0.02, 0.17) in those who received n-3 PUFAs compared
      with placebo, with strong evidence of heterogeneity (I(2) = 65%, P < 0.01). The
      presence of funnel plot asymmetry suggested that publication bias was a likely
      source of this heterogeneity. Depressive symptom severity and participant
      diagnosis also explained some of the observed heterogeneity. Greater effects of n
      3 PUFAs were found in individuals with more-severe depressive symptoms. In trials
      that enrolled individuals with a diagnosed depressive disorder, the combined mean
      difference was 0.41 (95% CI: 0.26, 0.55), although evidence of heterogeneity was
      also found (I(2) = 71%). In trials that enrolled individuals without a depressive
      diagnosis, no beneficial effects of n-3 PUFAs were found (largest combined mean
      difference: 0.22; 95% CI: -0.01, 0.44; I(2) = 0%). CONCLUSIONS: Trial evidence of
      the effects of n-3 PUFAs on depressed mood has increased but remains difficult to
      summarize because of considerable heterogeneity. The evidence available provides
      some support of a benefit of n-3 PUFAs in individuals with diagnosed depressive
      illness but no evidence of any benefit in individuals without a diagnosis of
      depressive illness.

PMID- 20130099
TI  - A novel MYBS3-dependent pathway confers cold tolerance in rice.
AB  - Rice (Oryza sativa) seedlings are particularly sensitive to chilling in early
      spring in temperate and subtropical zones and in high-elevation areas.
      Improvement of chilling tolerance in rice may significantly increase rice
      production. MYBS3 is a single DNA-binding repeat MYB transcription factor
      previously shown to mediate sugar signaling in rice. In this study, we observed
      that MYBS3 also plays a critical role in cold adaptation in rice. Gain- and loss
      of-function analyses indicated that MYBS3 was sufficient and necessary for
      enhancing cold tolerance in rice. Transgenic rice constitutively overexpressing
      MYBS3 tolerated 4 degrees C for at least 1 week and exhibited no yield penalty in
      normal field conditions. Transcription profiling of transgenic rice
      overexpressing or underexpressing MYBS3 led to the identification of many genes
      in the MYBS3-mediated cold signaling pathway. Several genes activated by MYBS3 as
      well as inducible by cold have previously been implicated in various abiotic
      stress responses and/or tolerance in rice and other plant species. Surprisingly,
      MYBS3 repressed the well-known DREB1/CBF-dependent cold signaling pathway in
      rice, and the repression appears to act at the transcriptional level. DREB1
      responded quickly and transiently while MYBS3 responded slowly to cold stress,
      which suggests that distinct pathways act sequentially and complementarily for
      adapting short- and long-term cold stress in rice. Our studies thus reveal a
      hitherto undiscovered novel pathway that controls cold adaptation in rice.

PMID- 20130100
TI  - Abscisic acid-induced resistance against the brown spot pathogen Cochliobolus
      miyabeanus in rice involves MAP kinase-mediated repression of ethylene signaling.
AB  - The plant hormone abscisic acid (ABA) is involved in an array of plant processes,
      including the regulation of gene expression during adaptive responses to various
      environmental cues. Apart from its well-established role in abiotic stress
      adaptation, emerging evidence indicates that ABA is also prominently involved in
      the regulation and integration of pathogen defense responses. Here, we
      demonstrate that exogenously administered ABA enhances basal resistance of rice
      (Oryza sativa) against the brown spot-causing ascomycete Cochliobolus miyabeanus.
      Microscopic analysis of early infection events in control and ABA-treated plants
      revealed that this ABA-inducible resistance (ABA-IR) is based on restriction of
      fungal progression in the mesophyll. We also show that ABA-IR does not rely on
      boosted expression of salicylic acid-, jasmonic acid -, or callose-dependent
      resistance mechanisms but, instead, requires a functional Galpha-protein. In
      addition, several lines of evidence are presented suggesting that ABA steers its
      positive effect on brown spot resistance through antagonistic cross talk with the
      ethylene (ET) response pathway. Exogenous ethephon application enhances
      susceptibility, whereas genetic disruption of ET signaling renders plants less
      vulnerable to C. miyabeanus attack, thereby inducing a level of resistance
      similar to that observed on ABA-treated wild-type plants. Moreover, ABA treatment
      alleviates C. miyabeanus-induced activation of the ET reporter gene EBP89, while
      derepression of pathogen-triggered EBP89 transcription via RNA interference
      mediated knockdown of OsMPK5, an ABA-primed mitogen-activated protein kinase
      gene, compromises ABA-IR. Collectively, these data favor a model whereby
      exogenous ABA enhances resistance against C. miyabeanus at least in part by
      suppressing pathogen-induced ET action in an OsMPK5-dependent manner.

PMID- 20130101
TI  - The role of heterologous chloroplast sequence elements in transgene integration
      and expression.
AB  - Heterologous regulatory elements and flanking sequences have been used in
      chloroplast transformation of several crop species, but their roles and
      mechanisms have not yet been investigated. Nucleotide sequence identity in the
      photosystem II protein D1 (psbA) upstream region is 59% across all taxa; similar
      variation was consistent across all genes and taxa examined. Secondary structure
      and predicted Gibbs free energy values of the psbA 5' untranslated region (UTR)
      among different families reflected this variation. Therefore, chloroplast
      transformation vectors were made for tobacco (Nicotiana tabacum) and lettuce
      (Lactuca sativa), with endogenous (Nt-Nt, Ls-Ls) or heterologous (Nt-Ls, Ls-Nt)
      psbA promoter, 5' UTR and 3' UTR, regulating expression of the anthrax protective
      antigen (PA) or human proinsulin (Pins) fused with the cholera toxin B-subunit
      (CTB). Unique lettuce flanking sequences were completely eliminated during
      homologous recombination in the transplastomic tobacco genomes but not unique
      tobacco sequences. Nt-Ls or Ls-Nt transplastomic lines showed reduction of 80% PA
      and 97% CTB-Pins expression when compared with endogenous psbA regulatory
      elements, which accumulated up to 29.6% total soluble protein PA and 72.0% total
      leaf protein CTB-Pins, 2-fold higher than Rubisco. Transgene transcripts were
      reduced by 84% in Ls-Nt-CTB-Pins and by 72% in Nt-Ls-PA lines. Transcripts
      containing endogenous 5' UTR were stabilized in nonpolysomal fractions. Stromal
      RNA-binding proteins were preferentially associated with endogenous psbA 5' UTR.
      A rapid and reproducible regeneration system was developed for lettuce commercial
      cultivars by optimizing plant growth regulators. These findings underscore the
      need for sequencing complete crop chloroplast genomes, utilization of endogenous
      regulatory elements and flanking sequences, as well as optimization of plant
      growth regulators for efficient chloroplast transformation.

PMID- 20130102
TI  - Complexation of arsenite with phytochelatins reduces arsenite efflux and
      translocation from roots to shoots in Arabidopsis.
AB  - Complexation of arsenite [As(III)] with phytochelatins (PCs) is an important
      mechanism employed by plants to detoxify As; how this complexation affects As
      mobility was little known. We used high-resolution inductively coupled plasma
      mass spectrometry and accurate mass electrospray ionization-mass spectrometry
      coupled to HPLC to identify and quantify As(III)-thiol complexes and free thiol
      compounds in Arabidopsis (Arabidopsis thaliana) exposed to arsenate [As(V)].
      As(V) was efficiently reduced to As(III) in roots. In wild-type roots, 69% of As
      was complexed as As(III)-PC4, As(III)-PC3, and As(III)-(PC2)2. Both the
      glutathione (GSH)-deficient mutant cad2-1 and the PC-deficient mutant cad1-3 were
      approximately 20 times more sensitive to As(V) than the wild type. In cad1-3
      roots, only 8% of As was complexed with GSH as As(III)-(GS)3 and no As(III)-PCs
      were detected, while in cad2-1 roots, As(III)-PCs accounted for only 25% of the
      total As. The two mutants had a greater As mobility, with a significantly higher
      accumulation of As(III) in shoots and 4.5 to 12 times higher shoot-to-root As
      concentration ratio than the wild type. Roots also effluxed a substantial
      proportion of the As(V) taken up as As(III) to the external medium, and this
      efflux was larger in the two mutants. Furthermore, when wild-type plants were
      exposed to l-buthionine sulfoximine or deprived of sulfur, both As(III) efflux
      and root-to-shoot translocation were enhanced. The results indicate that
      complexation of As(III) with PCs in Arabidopsis roots decreases its mobility for
      both efflux to the external medium and for root-to-shoot translocation. Enhancing
      PC synthesis in roots may be an effective strategy to reduce As translocation to
      the edible organs of food crops.

PMID- 20130104
TI  - Computational analysis of off-rate selection experiments to optimize affinity
      maturation by directed evolution.
AB  - Directed evolution is a powerful approach for isolating high-affinity binders
      from complex libraries. In affinity maturation experiments, binders with the
      highest affinities in the library are typically isolated through selections for
      decreased off rate using a suitable selection platform (e.g. phage display or
      ribosome display). In such experiments, the library is initially exposed to
      biotinylated antigen and the binding reaction is allowed to proceed. A large
      excess of unbiotinylated antigen is then added as a competitor to capture the
      vast majority of rapidly dissociating molecules; the slowly dissociating library
      members can subsequently be rescued by capturing the biotin-carrying complexes.
      To optimize the parameters for such affinity maturation experiments, we performed
      both deterministic and stochastic simulations of off-rate selection experiments
      using different input libraries. Our results suggest that the most critical
      parameters for achieving the lowest off rates after selection are the ratio of
      competitor antigen to selectable antigen and the selection time. Furthermore, the
      selection time has an optimum that depends on the experimental setup and the
      nature of the library. Notably, if selections are carried out for times much
      longer than the optimum, equilibrium is reached and the selection pressure is
      weakened or lost. Comparison of different selection strategies revealed that
      sequential selection rounds with lower stringency are favored over high
      stringency selection experiments due to enhanced diversity in the selected pools.
      Such simulations may be helpful in optimizing affinity maturation strategies and
      off-rate selection experiments.

PMID- 20130105
TI  - An improved yeast transformation method for the generation of very large human
      antibody libraries.
AB  - Antibody library selection by yeast display technology is an efficient and highly
      sensitive method to identify binders to target antigens. This powerful selection
      tool, however, is often hampered by the typically modest size of yeast libraries
      (approximately 10(7)) due to the limited yeast transformation efficiency, and the
      full potential of the yeast display technology for antibody discovery and
      engineering can only be realized if it can be coupled with a mean to generate
      very large yeast libraries. We describe here a yeast transformation method by
      electroporation that allows for the efficient generation of large antibody
      libraries up to 10(10) in size. Multiple components and conditions including
      CaCl(2), MgCl(2), sucrose, sorbitol, lithium acetate, dithiothreitol,
      electroporation voltage, DNA input and cell volume have been tested to identify
      the best combination. By applying this developed protocol, we have constructed a
      1.4 x 10(10) human spleen antibody library essentially in 1 day with a
      transformation efficiency of 1-1.5 x 10(8) transformants/microg vector DNA. Taken
      together, we have developed a highly efficient yeast transformation method that
      enables the generation of very large and productive human antibody libraries for
      antibody discovery, and we are now routinely making 10(9) libraries in a day for
      antibody engineering purposes.

PMID- 20130106
TI  - Engineering a two-helix bundle protein for folding studies.
AB  - The SAP domain from the Saccharomyces cerevisiae THO1 protein contains a
      hydrophobic core and just two alpha-helices. It could provide a system for
      studying protein folding that bridges the gap between studies on isolated helices
      and those on larger protein domains. We have engineered the SAP domain for
      protein folding studies by inserting a tryptophan residue into the hydrophobic
      core (L31W) and solved its structure. The helical regions had a backbone root
      mean-squared deviation of 0.9 A from those of wild type. The mutation L31W
      destabilised wild type by 0.8 +/- 0.1 kcal mol(-1). The mutant folded in a
      reversible, apparent two-state manner with a microscopic folding rate constant of
      around 3700 s(-1) and is suitable for extended studies of folding.

PMID- 20130107
TI  - Interferon-gamma secretion is induced in IL-12 stimulated human NK cells by
      recognition of Helicobacter pylori or TLR2 ligands.
AB  - Helicobacter pylori induce a chronic inflammation in the human gastric mucosa
      characterized by increased production of interferon-gamma (IFN-gamma). The
      presence of natural killer (NK) cells in the human gastric mucosa and the ability
      of NK cells to produce IFN-gamma suggest an important role of NK cells in the
      immune response directed towards H. pylori infection. Since NK cells previously
      have been shown to respond to bacterial components with IFN-gamma production, we
      investigated the mechanisms for the recognition of H. pylori. We found that
      inhibition of MyD88 homodimerization resulted in decreased production of IFN
      gamma and that inhibition of the p38 MAPK decreased the production as well as the
      secretion of IFN-gamma. Further studies indicated an involvement of Toll-like
      receptors (TLRs), in particular TLR2. Finally, we showed that the H. pylori
      specific membrane bound lipoprotein HpaA induced IFN-gamma production from NK
      cells through recognition by TLR2. In conclusion, we suggest an involvement of
      TLR2 in the recognition of H. pylori by human NK cells and that HpaA is a TLR2
      ligand important for recognition.

PMID- 20130108
TI  - 1H and hyperpolarized 3He magnetic resonance imaging clearly detect the
      preventative effect of a glucocorticoid on endotoxin-induced pulmonary
      inflammation in vivo.
AB  - INTRODUCTION: Proton (1H ) magnetic resonance imaging (MRI) can be utilized to
      quantify pulmonary edema in endotoxin-induced pulmonary inflammation and
      hyperpolarized (HP) 3He MRI can assess pulmonary ventilation. Neither of the
      methods has been applied to assess the impact of a drug on endotoxin-induced
      pulmonary inflammation in vivo. The aim of the current study was to evaluate the
      capability of 1H and HP 3He MRI to assess the effects of a glucocorticoid on
      endotoxin-induced pulmonary inflammation in vivo. MATERIALS AND METHODS: Mice
      were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min.
      Half of the endotoxin-exposed mice were pretreated with a glucocorticoid
      (budesonide 3 mg/kg; 2 times/day) and the other half with vehicle p.o. The first
      budesonide treatment was administered 1 h prior to the aerosol inhalation. Forty
      eight hours after the aerosol exposure, the mice were anaesthetized for
      subsequent imaging. Hyperpolarized 3He was administered and axial MR images of
      the lungs obtained. Matching 1H MR images were then acquired. The mice were
      sacrificed and broncho-alveolar lavage (BAL) samples were harvested to determine
      total and cell differential counts. RESULTS: The lesion volume on both 1H and 3He
      MRI, were markedly increased by endotoxin exposure (P<0.001). Budesonide strongly
      reduced lesion volume (P<0.001). The BAL cell count correlated strongly with both
      (3)He (P<0.001; r = 0.96) and 1H lesion volumes (P<0.001; r = 0.97). CONCLUSIONS:
      Hyperpolarized 3He MRI and 1H MRI clearly visualized the preventative effect of
      budesonide on the impact of endotoxin on pulmonary ventilation and edema,
      respectively. The fact that ventilation defects on 3He MRI corresponded to
      findings from conventional 1H MRI, as well as to counts of BAL inflammatory cells
      suggests that these imaging techniques constitute promising tools for non
      invasive monitoring of pulmonary inflammation in vivo.

PMID- 20130109
TI  - Modelling the likely effect of the increase of the upper age limit from 70 to 73
      for breast screening in the UK National Programme.
AB  - The UK National Breast Screening Programme is planned to have the age range for
      invitation to screening expanded from 50-70 to 47-73. At the upper limit, this
      represents one additional screen taking place in the early 70s. We aimed to
      estimate the likely effect of this on breast cancer mortality and on
      overdiagnosis of breast cancer. We used estimates of breast cancer incidence and
      survival by detection mode (screening or symptomatic), screening lead time and
      mortality from competing causes to estimate the likely numbers of breast cancer
      deaths prevented per 1000 women screened, using both a stochastic continuous time
      model and a semi-deterministic discrete time model. In the continuous model, we
      estimated that per 1000 women screened 1.2 deaths would be prevented and in the
      discrete model 0.91 deaths. In the latter model, we also estimated that there
      would be around 6.8 years of life saved per 1000 women screened and an additional
      two diagnoses of breast cancer. These results suggest that the expansion of the
      upper age limit will be cost-effective. They remain to be confirmed by evaluation
      of the age extension. They provide prior estimates that may inform the evaluation
      of the age extension.

PMID- 20130110
TI  - Dose-dependent attenuation of heroin self-administration with lobeline.
AB  - Behavioural studies have yielded results that show lobeline has the ability to
      attenuate d-methamphetamine self-administration. Further in vivo and in vitro
      studies have demonstrated a blockade of mu-opioid receptors with lobeline. The
      present investigation examined the ability of lobeline to attenuate heroin
      intravenous (i.v.) self-administration when administered prior to testing. Male
      Sprague-Dawley rats were surgically implanted with jugular catheters and trained
      to lever press for i.v. heroin infusions (18 microg/kg) under a fixed ratio-2
      schedule wherein two active lever presses resulted in heroin delivery. Rats then
      were tested for heroin self-administration after pretreatment with subcutaneous
      lobeline injections (0.3, 1.0, or 3.0 mg/kg, 15 min prior to testing sessions).
      At doses of 1.0 and 3.0 mg/kg, lobeline attenuated self-administration of heroin.
      The results suggest a potential for lobeline to be used in pharmacotherapy for
      opioid abuse.

PMID- 20130111
TI  - Disulfide isomerase glucose-regulated protein 58 is required for the nuclear
      localization and degradation of retinoic acid receptor alpha.
AB  - Retinoic acid receptor alpha (RARA) is critical for spermatogenesis, as shown by
      a sterility phenotype observed in Rara knockout mice. RARA is important in both
      Sertoli and germ cells of the testis. Here, we demonstrate that a disulfide
      isomerase glucose-regulated protein 58 (GRp58) participates in the nuclear import
      and degradation of RARA in Sertoli cells. GRp58 interacted with RARA in the
      presence of all-trans retinoic acid (ATRA) ligand and, as a complex, it was
      translocated from the cytoplasm to the nucleus and, then with time, GRp58
      dissociated from RARA and was found in the cytoplasm. The GRp58 RNAi treatment
      disrupted ATRA-dependent RARA nuclear localization, indicating the requirement of
      GRp58 for RARA nuclear localization. Moreover, treatment with sulfhydryl
      modifying agents that oxidize SH-groups of cysteine residues to disulfide bonds
      abolished ATRA-mediated RARA nuclear localization, suggesting that the thiol
      oxidoreductase activity of GRp58 may be required for RARA nuclear import.
      Additionally, the proteasome inhibitor treatment resulted in the co-localization
      of GRp58 and RARA at the endoplasmic reticulum (ER), suggesting that GRp58 may
      bring RARA to the ER for the ER-associated degradation (ERAD) of RARA before it
      is de-coupled from RARA for recycling. In this regard, proteasome inhibitor
      treatment also increased the interaction of RARA with UBE2J2, an ERAD-associated
      ubiquitin E2 enzyme. Collectively, the results indicate that GRp58 may act as a
      molecular chaperone that alters the protein conformation of RARA for its delivery
      to the nucleus and, then with time, accompanies RARA to the ER for RARA
      ubiquitination and proteasome-mediated ERAD.

PMID- 20130112
TI  - Influence of exposure route and oral dosage regimen on 1, 1-dichloroethylene
      toxicokinetics and target organ toxicity.
AB  - The objective of this investigation was to elucidate the effects of route of
      exposure and oral dosage regimen on the toxicokinetics (TK) of 1,1
      dichloroethylene (DCE). Fasted male Sprague-Dawley rats that inhaled 100 or 300
      ppm for 2 h absorbed total systemic doses of (10 or 30 mg/kg DCE, respectively.
      Other groups of rats received 10 or 30 mg/kg DCE by intravenous injection, bolus
      gavage (by mouth), or gastric infusion (g.i.) over a 2-h period. Serial
      microblood samples were taken from the cannulated, unanesthetized animals and
      analyzed for DCE content by gas chromatography to obtain concentration versus
      time profiles. Inhalation resulted in substantially higher peak blood
      concentrations and area under blood-concentration time curves (AUC(0)(2)) than
      did gastric infusion of the same dose over the same time frame at each dosage
      level, although inhalation (AUC(0)(infinity)) values were only modestly higher.
      Urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyltranspeptidase
      (GGT) activities were monitored as indices of kidney injury in the high-dose
      groups. NAG and GGT excretion were much more pronounced after inhalation than
      gastric infusion. Administration of DCE by gavage also produced much higher Cmax
      and AUC(0)(2) values than did 2-h g.i., although AUC(0)(infinity) values were not
      very different. The 30 mg/kg bolus dose produced marked elevation in serum
      sorbitol dehydrogenase, an index of hepatocellular injury. Administration of this
      dose by inhalation and gastric infusion was only marginally hepatotoxic. These
      findings demonstrate the TK and target organ toxicity of DCE vary substantially
      between different exposure routes, as well as dosage regimens, making direct
      extrapolations untenable in health risk assessments.

PMID- 20130113
TI  - Minireview: Mechano-growth factor: a putative product of IGF-I gene expression
      involved in tissue repair and regeneration.
AB  - The discovery that IGF-I mRNAs encoding isoforms of the pro-IGF-I molecule are
      differentially regulated in response to mechanical stress in skeletal muscle has
      been the impetus for a number of studies designed to demonstrate that alternative
      splicing of IGF-I pre-mRNA involving exons 4, 5, and 6 gives rise to a unique
      peptide derived from pro-IGF-I that plays a novel role in myoblast proliferation.
      Research suggests that after injury to skeletal muscle, the IGF-IEb mRNA splice
      variant is up-regulated initially, followed by up-regulation of the IGF-IEa
      splice variant at later time points. Up-regulation of IGF-IEb mRNA correlates
      with markers of satellite cell and myoblast proliferation, whereas up-regulation
      of IGF-IEa mRNA is correlated with differentiation to mature myofibers. Due to
      the apparent role of IGF-IEb up-regulation in muscle remodeling, IGF-IEb mRNA was
      also named mechano-growth factor (MGF). A synthetically manufactured peptide
      (also termed MGF) corresponding to the 24 most C-terminal residues of IGF-IEb has
      been shown to promote cellular proliferation and survival. However, no analogous
      peptide product of the Igf1 gene has been identified in or isolated from cultured
      cells, their conditioned medium, or in vivo animal tissues or biological fluids.
      This review will discuss the relationship of the Igf1 gene to MGF and will
      differentiate actions of synthetic MGF from any known product of Igf1.
      Additionally, the role of MGF in satellite cell activation, aging,
      neuroprotection, and signaling will be discussed. A survey of outstanding
      questions relating to MGF will also be provided.

PMID- 20130114
TI  - Toll-like receptor ligands cause proinflammatory and prodiabetic activation of
      adipocytes via phosphorylation of extracellular signal-regulated kinase and c-Jun
      N-terminal kinase but not interferon regulatory factor-3.
AB  - Here, we aim to investigate the mechanisms of Toll-like receptor (TLR)-induced
      prodiabetic and proinflammatory activation of adipocytes and to detect
      differences in the responsiveness of TLRs to their respective ligands between
      adipocytes isolated from inflamed vs. noninflamed adipose tissue. Experiments
      using specific ligands for all known TLRs were performed in murine 3T3-L1
      adipocytes and in human adipocytes isolated from noninflamed and inflamed adipose
      tissue. IL-6 and monocyte chemoattractant protein-1 (MCP-1) release were measured
      by ELISA. The expression of the signal transduction proteins phospho
      extracellular signal-regulated kinase (P-Erk), P-c-Jun N-terminal kinase (JNK),
      and P-interferon regulatory factor-3 was investigated by Western blot analysis.
      Additionally, functional inhibitors of MAPK kinase-1/-2 and JNK-1/-2 were used in
      the stimulation experiments. Activation of TRL4 by lipopolysaccharide (LPS) and
      TLR1/2 by Pam(3)Cys up-regulates IL-6 and MCP-1 release in adipocytes via
      specific activation of Erk. Stimulation of adipocytes by macrophage activating
      lipopeptide-2 (MALP-2) induces MCP-1 but has no effect on IL-6 release. This
      stimulatory effect on MCP-1 release is antagonized by inhibition of both mitogen
      activated protein kinase-1/-2 and JNK-1/-2. Phosphorylation of Erk and JNK is up
      regulated after stimulation by MALP-2. In human adipocytes isolated from
      noninflamed adipose tissue, LPS and Pam(3)Cys, but not MALP-2, are potent
      inducers of IL-6 and MCP-1. MALP-2 is able to induce IL-6 and MCP-1 release in
      adipocytes isolated from inflamed adipose tissue, whereas these adipocytes lost
      their ability to respond to LPS. The present results point to a role of the
      adipose tissue in innate immunity. TLR-ligand-induced proinflammatory and
      prodiabetic activation of adipocytes might couple visceral adipose tissue
      dysfunction with insulin resistance and type 2 diabetes mellitus.

PMID- 20130115
TI  - Hydroxysteroid (17{beta}) dehydrogenase 12 is essential for mouse organogenesis
      and embryonic survival.
AB  - Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) have a significant role in
      steroid metabolism by catalyzing the conversion between 17-keto and 17beta
      hydroxysteroids. However, several studies in vitro have shown that some of these
      enzymes may also be involved in other metabolic pathways. Among these enzymes,
      HSD17B12 has been shown to be involved in both the biosynthesis of estradiol and
      the elongation of the essential very long fatty acids in vitro and in vivo. To
      investigate the function of mammalian HSD17B12 in vivo, we generated mice with a
      null mutation of the Hsd17b12 gene (HSD17B12KO mice) by using a gene-trap vector,
      resulting in the expression of the lacZ gene of the trapped allele. The beta
      galactosidase staining of the heterozygous HSD17B12KO mice revealed that Hsd17b12
      is expressed widely in the embryonic day (E) 7.5-E9.5 embryos, with the highest
      expression in the neural tissue. The HSD17B12KO mice die at E9.5 at latest and
      present severe developmental defects. Analysis of the knockout embryos revealed
      that the embryos initiate gastrulation, but organogenesis is severely disrupted.
      As a result, the E8.5-E9.5 embryos were void of all normal morphological
      structures. In addition, the inner cell mass of knockout blastocysts showed
      decreased proliferation capacity in vitro, and the amount of arachidonic acid was
      significantly decreased in heterozygous HSD17B12 ES cells. This, together with
      the expression pattern, suggests that in mouse, the HSD17B12 is involved in the
      synthesis of arachidonic acid and is essential for normal neuronal development
      during embryogenesis.

PMID- 20130116
TI  - Intestinal and hepatic cholesterol carriers in diabetic Psammomys obesus.
AB  - Insulin resistance and type 2 diabetes (T2D) are characterized by hyperlipidemia.
      The aim of the present study was to elucidate whether T2D contributes to abnormal
      cholesterol (CHOL) homeostasis. Experiments were carried out in the small
      intestine and liver of Psammomys obesus, a model of nutritionally induced T2D.
      Our results show that diabetic animals exhibited a lower intestinal CHOL uptake,
      which was associated with a decrease in 1) the gene and protein expression of
      Niemann-Pick C1 like 1 that plays a pivotal role in CHOL incorporation in the
      enterocytes; and 2) mRNA of ATP-binding cassette transporters (ABC)A1 that
      mediates CHOL efflux from intestinal cells to apolipoprotein A-I and high-density
      lipoprotein. No changes were observed in the other intestinal transporters
      scavenger receptor-class B type I (SR-BI) and annexin 2. On the other hand, in
      diabetic animals, a significant mRNA decrease was noticed in intestinal ABCG5 and
      ABCG8 responsible for the secretion of absorbed CHOL back into the lumen.
      Furthermore, jejunal PCSK9 protein was diminished and low-density lipoprotein
      receptor was raised, along with a significant down-regulation in jejunal 3
      hydroxy-3-methylglutaryl-coenzyme A reductase in P. obesus with T2D. Finally,
      among the transcription factors tested, only an increase in liver X receptors
      alpha and a decrease in peroxisome proliferator-activated receptors delta/beta
      mRNAs were detected in the intestine. In the liver, there was 1) an augmentation
      in the protein mass of Niemann-Pick C1 like 1, SR-BI, and annexin 2; 2) an up
      regulation of SR-BI mRNA; 3) a fall in ABCG8 protein content as well as in ABCG5
      and ABCA1 mRNA; and 4) an augmentation in liver X receptors alpha and peroxisome
      proliferator-activated receptors beta/delta mRNA, together with a drop in sterol
      regulatory element binding protein-2 protein. Our findings show that the
      development in P. obesus with T2D modifies the whole intraenterocyte and
      hepatocyte machinery responsible for CHOL homeostasis.

PMID- 20130117
TI  - Dehydration-induced increase in aquaporin-2 protein abundance is blocked by
      nonsteroidal anti-inflammatory drugs.
AB  - It is now well established that the antidiuretic response to vasopressin is
      modulated by changes in aquaporin-2 (AQP2) expression in response to hydration
      status. While vasopressin itself is one signal driving expression, other signals
      also play a part. In this study, we planned to investigate whether
      prostaglandins, known to modulate AQP2 trafficking, may play a role in this
      process. Male Wistar rats were kept in metabolic cages, with either free access
      to water and food, or were given 15 g of food gelled with water, such that they
      were fluid restricted or fluid loaded. The effects of oral administration of two
      structurally different NSAIDs, indomethacin and ibuprofen, and a COX-2-selective
      NSAID, meloxicam, on urine output and AQP2 expression were investigated in
      kidneys removed under terminal anesthesia. All the NSAIDs decreased AQP2
      expression significantly in water-restricted rats but did not significantly alter
      PGE excretion. In water-loaded rats, the effects were less marked, and meloxicam
      had no significant effect. Consistent with this, ibuprofen prevented the increase
      in AQP2 expression seen in response to dehydration. These results demonstrate
      that NSAIDs decrease AQP2 protein abundance, particularly during adaptation
      during dehydration. This may be of particular significance in older and
      critically ill patients, who are prone to dehydration.

PMID- 20130118
TI  - A metabolomics approach using juvenile cystic mice to identify urinary biomarkers
      and altered pathways in polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited
      kidney disease and affects 1 in 1,000 individuals. Ultrasound is most often used
      to diagnose ADPKD; such a modality is only useful late in the disease after
      macroscopic cysts are present. There is accumulating evidence suggesting that
      there are common cellular and molecular mechanisms responsible for cystogenesis
      in human and murine PKD regardless of the genes mutated, and, in the case of
      complex metabolomic analysis, the use of a mouse model has distinct advantages
      for proof of principle over a human study. Therefore, in this study we utilized a
      urinary metabolomics-based investigation using gas chromatography-time of flight
      mass spectrometry to demonstrate that the cystic mouse can be discriminated from
      its wild-type counterpart by urine analysis alone. At day 26 of life, before
      there is serological evidence of kidney dysfunction, affected mice are
      distinguishable by urine metabolomic analysis; this finding persists through 45
      days until 64 days, at which time body weight differences confound the results.
      Using functional score analysis and the KEGG pathway database, we identify
      several biologically relevant metabolic pathways which are altered very early in
      this disease, the most highly represented being the purine and galactose
      metabolism pathways. In addition, we identify several specific candidate
      biomarkers, including allantoic acid and adenosine, which are augmented in the
      urine of young cystic mice. These markers and pathway components, once extended
      to human disease, may prove useful as a noninvasive means of diagnosing cystic
      kidney diseases and to suggest novel therapeutic approaches. Thus, urine
      metabolomics has great diagnostic potential for cystic renal disorders and
      deserves further study.

PMID- 20130119
TI  - Modulation of ureteric Ca signaling and contractility in humans and rats by
      uropathogenic E. coli.
AB  - Ascending urinary tract infections, a significant cause of kidney damage, are
      predominantly caused by uropathogenic Escherichia coli (UPEC). However, the role
      and mechanism of changes in ureteric function during infection are poorly
      understood. We therefore investigated the effects of UPEC on Ca signaling and
      contractions in rat (n = 17) and human (n = 6) ureters. Ca transients and force
      were measured and effects of UPEC on the urothelium were monitored in live
      tissues. In both species, luminal exposure of ureters to UPEC strains J96 and 536
      caused significant time-dependent decreases in phasic and high K depolarization
      induced contractility, associated with decreases in the amplitude and duration of
      the Ca transients. These changes were significant after 3-5 h and irreversible
      over the next 5 h. The infection causes increased activity of K channels, causing
      inhibition of voltage-gated Ca entry, and K channel blockers could reverse the
      effects of UPEC on ureteric function. A smaller direct effect on Ca entry also
      occurs. Nonpathogenic E. coli (TG2) or abluminal application of UPEC did not
      produce changes in Ca signaling or contractility. UPEC exposure also caused
      significant impairment of urothelial barrier function; luminal application of the
      Ca channel blocker nifedipine caused a reduction in contractions as it entered
      the tissue, an effect not observed in untreated ureters. Thus, UPEC impairs
      ureteric contractility in a Ca-dependent manner, largely caused by stimulation of
      potassium channels and this mechanism is dependent on host-urothelium
      interaction.

PMID- 20130120
TI  - Regulation of renal proximal tubule Na-K-ATPase by prostaglandins.
AB  - Prostaglandins (PGs) play a number of roles in the kidney, including regulation
      of salt and water reabsorption. In this report, evidence was obtained for
      stimulatory effects of PGs on Na-K-ATPase in primary cultures of rabbit renal
      proximal tubule (RPT) cells. The results of our real-time PCR studies indicate
      that in primary RPTs the effects of PGE(2), the major renal PG, are mediated by
      four classes of PGE (EP) receptors. The role of these EP receptors in the
      regulation of Na-K-ATPase was examined at the transcriptional level. Na-K-ATPase
      consists of a catalytic alpha-subunit encoded by the ATP1A1 gene, as well as a
      beta-subunit encoded by the ATP1B1 gene. Transient transfection studies conducted
      with pHbeta1-1141 Luc, a human ATP1B1 promoter/luciferase construct, indicate
      that both PGE(1) and PGE(2) are stimulatory. The evidence for the involvement of
      both the cAMP and Ca(2+) signaling pathways includes the inhibitory effects of
      the myristolylated PKA inhibitor PKI, the adenylate cyclase (AC) inhibitor
      SQ22536, and the PKC inhibitors Go 6976 and Ro-32-0432 on the PGE(1) stimulation.
      Other effectors that similarly act through cAMP and PKC were also stimulatory to
      transcription, including norepinephrine and dopamine. In addition to its effects
      on transcription, a chronic incubation with PGE(1) was observed to result in an
      increase in Na-K-ATPase mRNA levels as well as an increase in Na-K-ATPase
      activity. An acute stimulatory effect of PGE(1) on Na-K-ATPase was observed and
      was associated with an increase in the level of Na-K-ATPase in the basolateral
      membrane.

PMID- 20130122
TI  - 2010 renal section awardees. 2010 Robert W. Berliner Award for Excellence in
      Renal Physiology.

PMID- 20130121
TI  - CDK inhibitor p21 is prosurvival in adriamycin-induced podocyte injury, in vitro
      and in vivo.
AB  - In response to injury, the highly specialized and terminally differentiated
      glomerular visceral epithelial cell, or podocyte, may undergo several cell fates,
      including dedifferentiation and proliferation, persistent cell cycle arrest,
      hypertrophy, apoptosis, or necrosis. Common to these potential outcomes of injury
      is their ultimate regulation at the level of the cell cycle. There is now a large
      body of literature confirming the importance of cell cycle regulatory proteins in
      the cellular response to injury. Although CDK inhibitor p21 levels increase in
      podocytes following injury, the role of p21 is unclear in focal segmental
      glomerulosclerosis (FSGS), in part because its function depends heavily on the
      cytotoxic stimulus and the cellular context. Adriamycin (ADR) is a podocyte toxin
      used to induce experimental FSGS. The purpose of this study was to define the
      role of p21 in ADR-induced podocyte injury. BALB/c mice, a strain carrying the
      recessive ADR susceptibility gene, were backcrossed against c57B6 p21-/- mice to
      yield a 12th generation BALB/c p21-/- strain. Experimental FSGS was induced by
      injection of ADR 12 mg/kg * 2 doses (n = 8/group), with mice killed at 1, 2, 8,
      and 11 wk. Diseased p21-/- mice demonstrated worse albuminuria, more widespread
      glomerulosclerosis, and higher blood urea nitrogen compared with diseased p21+/+
      mice. In diseased p21-/- mice vs. p21+/+ mice, apoptosis [measured by TdT
      mediated dUTP nick end labeling (TUNEL) assay] was increased, and podocyte number
      (measured by WT-1 immunostaining) was decreased. To validate these findings in
      vitro, we utilized differentiated mouse podocytes, p21-/- and p21+/+, exposed to
      0.125 MUg/ml ADR. Apoptosis, measured by Hoechst 33342 staining and TUNEL assay,
      was greater in cultured p21-/- podocytes compared with p21+/+ podocytes.
      Reconstitution of p21 via retroviral transfection rescued the p21-/- podocytes
      from apoptosis. We conclude that p21 is prosurvival in the podocyte's response to
      ADR-induced injury. Ongoing studies are defining the mechanisms of this
      protective effect as it relates to DNA damage and apoptosis.

PMID- 20130123
TI  - ANG II receptor antagonists as modulators of macrophages polarization.

PMID- 20130124
TI  - NO solution for a radical problem: a TAL story.

PMID- 20130125
TI  - Taenia saginata metacestode antigenic fractions without affinity to concanavalin
      A are an important source of specific antigens for the diagnosis of human
      neurocysticercosis.
AB  - Taenia saginata metacestode antigens have been constituted a useful alternative
      antigen for neurocysticercosis (NC) serodiagnosis, particularly due to an
      increasing difficulty to obtain Taenia solium homologous antigen. Cross
      reactivity with Echinococcus granulosus infection occurs in homologous and
      heterologous antigens and could be avoided by using different purified methods.
      The present study evaluated antigen fractions obtained from saline extracts of T.
      saginata metacestodes purified by affinity chromatography with jacalin or
      concanavalin A (ConA) lectins to detect IgG antibodies by enzyme-linked
      immunosorbent assay (ELISA) and immunoblot analysis to diagnose human NC. Serum
      samples were collected from 142 individuals: 40 of them were diagnosed with NC,
      62 presented Taenia sp. and other parasites, and 40 were apparently healthy
      individuals. The jacalin- and ConA-unbound fractions demonstrated sensitivity and
      specificity higher than those of bound fractions. Among unbound fractions, ConA
      demonstrated statistically higher sensitivity and specificity by ELISA (90% and
      93.1%, respectively). By immunoblot assay, the 64- to 68-kDa component from the
      ConA-unbound fraction showed 100% sensitivity and specificity, making this
      component suitable for use as a specific antigen for diagnosis of NC. To our
      knowledge, this is the first report showing the relevance of using the unbound
      ConA fraction of T. saginata metacestodes to diagnose NC. In conclusion, the
      results obtained herein clearly demonstrate that antigenic fractions without
      affinity to ConA, obtained from T. saginata metacestodes, are an important source
      of specific peptides and are efficient in the diagnosis of NC when tested by
      immunoblot assay.

PMID- 20130126
TI  - Effects of psychological stress and fluoxetine on development of oral candidiasis
      in rats.
AB  - Psychological stress has been found to suppress cell-mediated immune responses
      that are important for limiting the proliferation of Candida albicans. Fluoxetine
      has been observed to reduce negative consequences of stress on the immune system
      in experimental and clinical models, but there are no data on its effects on oral
      candidiasis. We designed experiments to evaluate the effects of fluoxetine on the
      development of oral candidiasis in Sprague-Dawley rats exposed to a chronic
      auditory stressor. Animals were submitted to surgical hyposalivation in order to
      facilitate the establishment and persistence of C. albicans infection. Stress
      application and treatment with drugs (placebo or fluoxetine) were initiated 7
      days before C. albicans inoculation and lasted until the end of the experiments,
      on day 15 postinoculation. Establishment of C. albicans infection was evaluated
      on days 2 and 15 after inoculation. Tissue injury was determined by the
      quantification of the number and type (normal or abnormal) of papillae on the
      dorsal tongue per microscopic field. A semiquantitative scale was devised to
      assess the degree of colonization of the epithelium by fungal hyphae. Our results
      showed that stress exacerbates C. albicans infection in the tongues of rats.
      Significant increases in Candida counts, the percentage of the tongue's surface
      covered with clinical lesions, the percentage of abnormal papillae, and the
      colonization of the epithelium by hyphae were found in stressed rats compared to
      the nonstressed ones. Treatment with fluoxetine significantly reversed these
      adverse effects of stress. Besides the psychopharmacological properties of
      fluoxetine against stress, it has consequences for Candida infection.

PMID- 20130127
TI  - Pattern of serum cytokine expression and T-cell subsets in sickle cell disease
      patients in vaso-occlusive crisis.
AB  - The pathogenesis of sickle vaso-occlusive crisis (VOC) in sickle cell disease
      (SCD) patients involves the accumulation of rigid sickle cells and the
      stimulation of an ongoing inflammatory response, as well as the stress of
      infections. The immune response, via cytokine imbalances and deregulated T-cell
      subsets, also has been proposed to contribute to the development of VOC. In this
      study, a panel of high-sensitivity cytokine kits was used to investigate
      cytokines in the sera of SCD patients in VOC. The results were compared primarily
      with those for stable SCD patients and secondarily with those for normal healthy
      people who served as controls. The cytokines studied included interleukin-2 (IL
      2), IL-4, and IL-10. Lymphocyte subsets of patients with VOC were also studied
      and were compared with those of both control groups (20 stable patients without
      crisis [SCD group] and 20 normal healthy controls [NHC]). The VOC group was
      notable for remarkably elevated levels of IL-4, among the three cytokines tested,
      compared with those for the SCD and NHC groups. Patients with VOC also differed
      from stable SCD patients and NHC by having notably lower IL-10 levels, as well as
      the lowest ratio of CD4(+) to CD8(+) T cells (0.7). The patterns of the
      proinflammatory cytokine IL-2 did not differ between VOC and stable SCD patients,
      but NHC had significantly lower IL-2 levels than both the VOC and SCD groups. Our
      results demonstrate coexisting levels, both high and low, of TH1- and TH2-type
      cytokines, as well as diminished levels of T-cell subsets in VOC. These results
      are discussed in an effort to better understand the importance of the immune
      system profile in the pathogenesis of sickle cell VOC. Since the possibility that
      a cytokine imbalance is implicated in the pathogenesis of sickle cell crisis has
      been raised, our results should prompt further investigation of the host immune
      response in terms of TH1 and TH2 balance in sickle cell crisis.

PMID- 20130128
TI  - Comparative measurement of cell-mediated immune responses of swine to the M and N
      proteins of porcine reproductive and respiratory syndrome virus.
AB  - The principal objectives of this study were to develop autologous antigen
      presenting cells (APCs) and to characterize the antigen-specific T-cell responses
      to the M and N proteins of porcine reproductive and respiratory syndrome virus
      (PRRSV) by using those APCs in outbred pigs. The orf6 and orf7 genes fused with
      porcine granulocyte-macrophage colony-stimulating factor (GM-CSF) were cloned
      into the mammalian expression vector to generate two plasmid DNAs, namely,
      pcDNA3.1-GM-CSF-PRRSV-M and pcDNA3.1-GM-CSF-PRRSV-N. Three of six pigs in two
      groups were repeatedly immunized with either plasmid DNA construct, and four pigs
      were used as controls. The recombinant M and N proteins fused with the protein
      transduction domain (PTD) of the human immunodeficiency virus type 1
      transactivator of transcription protein were employed to generate major
      histocompatibility complex-matched autologous APCs from each pig. The levels of T
      cell proliferation and gamma interferon (IFN-gamma) synthesis were compared
      between pigs immunized with the two plasmid DNAs after stimulation of the
      peripheral blood mononuclear cells (PBMCs) of each pig with the autologous
      antigen-presenting dendritic cells and PBMCs. Higher levels of T-cell
      proliferation and IFN-gamma synthesis were identified in PBMCs isolated from the
      pigs immunized with pcDNA3.1-GM-CSF-PRRSV-M than in those isolated from the pigs
      immunized with pcDNA3.1-GM-CSF-PRRSV-N. By way of contrast, serum antibodies were
      detected only in pigs immunized with pcDNA3.1-GM-CSF-PRRSV-N. However, no T-cell
      response or antibody production was detected in the control pigs. These results
      suggest that the M protein of PRRSV is a more potent T cell-stimulating antigen
      than the N protein. Nevertheless, it should be emphasized that the N protein
      substantially induces both cellular and humoral immune responses. The newly
      developed protocol for generating self APCs may prove effective in further
      efforts to characterize additional PRRSV proteins involved in the induction of
      cell-mediated immunity.

PMID- 20130129
TI  - Optimization and application of a multiplex bead-based assay to quantify serotype
      specific IgG against Streptococcus pneumoniae polysaccharides: response to the
      booster vaccine after immunization with the pneumococcal 7-valent conjugate
      vaccine.
AB  - We describe the optimization and application of a multiplex bead-based assay
      (Luminex) to quantify antibodies against polysaccharides of 13 pneumococcal
      serotypes. In the optimized multiplex immunoassay (MIA), intravenous immune
      globulin was introduced as an in-house reference serum, and nonspecific reacting
      antibodies were adsorbed with the commercial product pneumococcal C
      polysaccharides Multi. The antibody concentrations were assessed in 188 serum
      samples obtained pre- and post-booster vaccination at 11 months after
      administration of a primary series of the pneumococcal seven-valent conjugate
      vaccine (PCV-7) at 2, 3, and 4 months of age. The results of the MIA were
      compared with those of the ELISA for the serotypes included in the seven-valent
      conjugated polysaccharide vaccine and for a non-vaccine serotype, serotype 6A.
      The geometric mean concentrations of the antibodies determined by MIA were
      slightly higher than those determined by ELISA. The correlations between the
      assays were good, with R(2) values ranging from 0.84 to 0.91 for all serotypes
      except serotype 19F, for which R(2) was 0.70. The concentrations of antibody
      against serotype 6A increased after the administration of PCV-7 due to cross
      reactivity with serotype 6B. The differences between the results obtained by
      ELISA and MIA suggest that the internationally established protective threshold
      of 0.35 microg/ml should be reevaluated for use in the MIA and may need to be
      amended separately for each serotype.

PMID- 20130130
TI  - Progesterone and 17beta-estradiol enhance regulatory responses to human
      papillomavirus type 16 virus-like particles in peripheral blood mononuclear cells
      from healthy women.
AB  - Human papillomavirus (HPV) virus-like particle (VLP) vaccines are highly
      effective at preventing viral infections and the development of precancerous
      lesions through the induction of high-titer neutralizing antibodies and strong
      cell-mediated immune responses. Women taking combined oral contraceptives (COCs),
      however, show large variabilities in the magnitudes of their antibody responses.
      The goal of the present study was to determine the effects of 17beta-estradiol
      (E2) and progesterone (P4) alone and in combination on the cellular immune
      response to HPV type 16 (HPV-16) VLPs in vitro. Peripheral blood mononuclear
      cells (PBMCs) from healthy donor women were stimulated in vitro with HPV-16 VLPs
      (2.5 microg/ml) in the presence of E2 and P4 administered either alone or in
      combination; and lymphoproliferation, cytokine production, transcription factor
      expression, and steroid hormone receptor expression were analyzed. HPV-16 VLPs
      significantly increased the levels of lymphoproliferation, proinflammatory
      cytokine (gamma interferon [IFN-gamma], interleukin-1beta [IL-1beta], IL-2, IL-6,
      IL-8, IL-12p70, IL-17, tumor necrosis factor alpha [TNF-alpha]) production, anti
      inflammatory cytokine (IL-1ra, IL-10) production, and the expression of Eralpha
      and Erbeta but decreased the levels of Foxp3 expression and production of
      transforming growth factor beta (TGF-beta). Exposure of PBMCs to E2 and P4 either
      alone or in combination significantly decreased the levels of lymphoproliferation
      and production of proinflammatory cytokines (IFN-gamma, IL-12p70, TNF-alpha) but
      increased the levels of production of IL-10 and TGF-beta and the expression of
      Foxp3 in response to HPV-16 VLPs. Treatment of cells with biologically relevant
      concentrations of sex steroid hormones suppressed the inflammatory response and
      enhanced the regulatory response to HPV-16 VLPs, which may have implications for
      predicting the long-term efficacy of HPV vaccines, adverse events, and cross
      protection among women taking COCs.

PMID- 20130131
TI  - Genomic features and evolutionary constraints in Saffold-like cardioviruses.
AB  - This study identified the complete genomic sequence of four type 2 and type 3
      human Saffold-like cardioviruses (SLCVs) isolated in Germany and Brazil. The
      secondary structures of the SLCV internal ribosome entry sites (IRESs) were
      deduced based on RNA base-pairing conservation and co-variation, using an
      established Theiler's murine encephalomyelitis virus (TMEV) IRES structure as a
      reference. The SLCV IRES was highly similar to that of TMEV, but motifs critical
      in TMEV for binding of the polypyrimidine tract-binding protein (PTB) were
      disrupted. In TMEV, corresponding alterations have been associated with reduced
      neurovirulence in mice. In the non-structural genome region, there was evidence
      of multiple intertypic recombination events between different SLCV types. Between
      viruses of the same type, recombination also occurred in the capsid-encoding
      genome region. There were apparently no recombination events between mouse TMEV
      and human SLCV. In another genus of the family Picornaviridae, Enterovirus,
      natural recombination occurs strictly within species and can serve as an
      additional criterion for delimiting species. Accordingly, the results of this
      study suggest that SLCV and TMEV may represent distinct species within the genus
      Cardiovirus.

PMID- 20130132
TI  - A mutation in H5 haemagglutinin that conferred human receptor recognition is not
      maintained stably during duck passage.
AB  - A/Hong Kong/213/97 (HK213; H5N1), isolated from a human, binds to both avian- and
      human-type receptors, due to a haemagglutinin (HA) mutation probably acquired
      during adaptation to humans. Duck passage of this virus conferred lethality in
      ducks. Sequence analyses of the duck-passaged virus revealed that its HA gene
      reverted back to one recognizing only avian-type receptors, and consequently it
      bound human tissue to a lesser extent. This finding suggests that viruses with
      human-type receptor specificity are unlikely to be maintained in waterfowl,
      unlike those with the human-type PB2 mutation, such as H5N1 viruses of the
      Qinghai Lake lineage.

PMID- 20130133
TI  - Hepatitis C virus genotype-3a core protein enhances sterol regulatory element
      binding protein-1 activity through the phosphoinositide 3-kinase-Akt-2 pathway.
AB  - Hepatitis C virus genotype-3a (HCV-3a) is directly linked to the development of
      steatosis. We previously showed that, through sterol regulatory element binding
      protein-1 (SREBP-1), HCV-3a core protein upregulates the promoter activity of
      fatty acid synthase, a major enzyme involved in de novo lipid synthesis. In this
      study, we investigated whether HCV-3a core can activate SREBP-1 and studied the
      role of phosphoinositide 3-kinase (PI3K)-Akt-2 pathway in modulating SREBP-1
      activity by HCV-3a core. To determine whether HCV-3a core could activate SREBP-1,
      the level of mature SREBP-1 was analysed by Western blotting. Our results showed
      that the level of mature SREBP-1 was enhanced by HCV-3a core protein after
      transient expression and in the chimeric HCV-3a core/1b replicon cells in
      comparison to controls. To investigate the role of the PI3K-Akt-2 pathway in
      SREBP-1 activation by HCV-3a core, PI3K and Akt-2 activity was inhibited by using
      the chemical inhibitor LY294002, a dominant-negative Akt-2 plasmid, or knockdown
      of Akt-2 by small hairpin RNA. Our results showed that inhibition of PI3K and Akt
      2 was associated with reduced SREBP-1 activation by HCV-3a core. These results
      indicate a role for PI3K and Akt-2 in increasing SREBP-1 activity by HCV-3a core
      protein and provide a mechanism of steatosis caused by HCV.

PMID- 20130134
TI  - An inactivated Vero cell-grown Japanese encephalitis vaccine formulated with
      Advax, a novel inulin-based adjuvant, induces protective neutralizing antibody
      against homologous and heterologous flaviviruses.
AB  - Advax is a polysaccharide-based adjuvant that potently stimulates vaccine
      immunogenicity without the increased reactogenicity seen with other adjuvants.
      This study investigated the immunogenicity of a novel Advax-adjuvanted Vero cell
      culture candidate vaccine against Japanese encephalitis virus (JEV) in mice and
      horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV
      antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity
      comparable to that elicited with live ChimeriVax-JE immunization and superior to
      that elicited with tenfold higher doses of a traditional non-adjuvanted JEV
      vaccine (JE-VAX; Biken Institute) or a newly approved alum-adjuvanted vaccine
      (Jespect; Novartis). Mice vaccinated with the Advax-adjuvanted, but not the
      unadjuvanted vaccine, were protected against live JEV challenge. Equine
      immunizations against JEV with Advax-formulated vaccine similarly showed enhanced
      vaccine immunogenicity, confirming that the adjuvant effects of Advax are not
      restricted to rodent models. Advax-adjuvanted JEV vaccine elicited a balanced T
      helper 1 (Th1)/Th2 immune response against JEV with protective levels of cross
      neutralizing antibody against other viruses belonging to the JEV serocomplex,
      including Murray Valley encephalitis virus (MVEV). The adjuvanted JEV vaccine was
      well tolerated with minimal reactogenicity and no systemic toxicity in immunized
      animals. The cessation of manufacture of traditional mouse brain-derived
      unadjuvanted JEV vaccine in Japan has resulted in a JEV vaccine shortage
      internationally. There is also an ongoing lack of human vaccines against other
      JEV serocomplex flaviviruses, such as MVEV, making this adjuvanted, cell culture
      grown JEV vaccine a promising candidate to address both needs with one vaccine.

PMID- 20130135
TI  - Generation of cytotoxic T-cell lines using overlapping pentadecapeptides derived
      from conserved regions of the adenovirus hexon protein.
AB  - Many of the 51 serotypes of adenovirus have been associated with clinically
      relevant infection. Adenovirus can disseminate rapidly in patients with a
      compromised immune system, such as that which occurs secondary to haematopoietic
      progenitor-cell transplantation. The higher rate of infection in recipients of T
      cell-depleted grafts and in those undergoing T cell-targeted treatment during
      graft versus host disease demonstrates the importance of a T-cell response in
      preventing disseminated infection. Studies have shown that the memory response to
      adenovirus is directed primarily to the hexon protein and is dominated by CD4+ T
      cells, probably due to the ability of the virus to block its presentation on HLA
      class I antigens. We have developed an approach to expand adenovirus-specific T
      cells using a pool of overlapping pentadecapeptides derived from selected
      conserved regions of hexon. We characterized responses to identify the peptides
      that are recognized, the responding T-cell subsets and their HLA restriction. Of
      eight lines that were characterized extensively, seven included both CD4+ and
      CD8+ T cells and each recognized between two and eight unique peptide sequences.
      By focusing the response on the conserved sequences of hexon, the cell lines are
      likely to recognize most of the serotypes responsible for clinically relevant
      disease. The 15 aa peptides used to prime the responses are more likely than
      whole virus or longer peptides to expand the less frequent CD8+ memory subset.
      Lines prepared by using our method may be more effective in adoptive
      immunotherapy protocols designed to prevent or treat disseminated adenovirus
      infections in high-risk patients.

PMID- 20130136
TI  - Measles virus M protein-driven particle production does not involve the endosomal
      sorting complex required for transport (ESCRT) system.
AB  - Assembly and budding of enveloped RNA viruses rely on viral matrix (M) proteins
      and host proteins involved in sorting and vesiculation of cellular cargoes, such
      as the endosomal sorting complex required for transport (ESCRT). The measles
      virus (MV) M protein promotes virus-like particle (VLP) production, and we now
      show that it shares association with detergent-resistant or tetraspanin-enriched
      membrane microdomains with ebolavirus VP40 protein, yet accumulates less
      efficiently at the plasma membrane. Unlike VP40, which recruits ESCRT components
      via its N-terminal late (L) domain and exploits them for particle production, the
      M protein does this independently of this pathway, as (i) ablation of motifs
      bearing similarity to canonical L domains did not affect VLP production, (ii) it
      did not redistribute Tsg101, AIP-1 or Vps4A to the plasma membrane, and (iii)
      neither VLP nor infectious virus production was sensitive to inhibition by
      dominant-negative Vps4A. Importantly, transfer of the VP40 L domain into the MV M
      protein did not cause recruitment of ESCRT proteins or confer sensitivity of VLP
      release to Vps4A, indicating that MV particle production occurs independently of
      and cannot be routed into an ESCRT-dependent pathway.

PMID- 20130137
TI  - The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by
      negatively regulating the JNK pathway via ASK1.
AB  - It has previously been reported that influenza A virus infection activates the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In addition, it has been shown
      that the mutant influenza A virus PR8-SH3-mf-1, which is unable to activate the
      PI3K/Akt pathway, is more pro-apoptotic than the wild-type (WT) virus. However,
      the molecular pathways involved in regulating this process remain unknown. Here,
      it is reported that, although both WT and PR8-SH3-mf-1 viruses induced apoptosis,
      the PR8-SH3-mf-1 virus consistently showed greater potential to induce
      mitochondrial membrane disruption, cytochrome c release, and translocation and
      conformational change of Bax than the WT virus. Furthermore, the PR8-SH3-mf-1
      virus was unable to phosphorylate apoptosis signal-regulating kinase 1 (ASK1) but
      induced higher levels of c-jun N-terminal kinase (JNK) phosphorylation than the
      WT virus. Blocking JNK activity could inhibit virus-induced Bax activation and
      apoptosis. These results reveal that, during influenza A virus infection, the
      PI3K/Akt pathway negatively regulates the JNK pathway via ASK1, thereby
      inhibiting JNK-dependent, Bax-mediated apoptosis.

PMID- 20130139
TI  - Signalling complexes and clusters: functional advantages and methodological
      hurdles.
AB  - Signalling molecules integrate, codify and transport information in cells.
      Organisation of these molecules in complexes and clusters improves the
      efficiency, fidelity and robustness of cellular signalling. Here, we summarise
      current views on how signalling molecules assemble into macromolecular complexes
      and clusters and how they use their physical properties to transduce
      environmental information into a variety of cellular processes. In addition, we
      discuss recent innovations in live-cell imaging at the sub-micrometer scale and
      the challenges of object (particle) tracking, both of which help us to observe
      signalling complexes and clusters and to examine their dynamic character.

PMID- 20130138
TI  - Matrix elasticity, cytoskeletal forces and physics of the nucleus: how deeply do
      cells 'feel' outside and in?
AB  - Cellular organization within a multicellular organism requires that a cell assess
      its relative location, taking in multiple cues from its microenvironment. Given
      that the extracellular matrix (ECM) consists of the most abundant proteins in
      animals and contributes both structure and elasticity to tissues, ECM probably
      provides key physical cues to cells. In vivo, in the vicinity of many tissue cell
      types, fibrous characteristics of the ECM are less discernible than the
      measurably distinct elasticity that characterizes different tissue
      microenvironments. As a cell engages matrix and actively probes, it senses the
      local elastic resistance of the ECM and nearby cells via their deformation, and-
      similar to the proverbial princess who feels a pea placed many mattresses below-
      the cell seems to possess feedback and recognition mechanisms that establish how
      far it can feel. Recent experimental findings and computational modeling of cell
      and matrix mechanics lend insight into the subcellular range of sensitivity.
      Continuity of deformation from the matrix into the cell and further into the
      cytoskeleton-caged and -linked nucleus also supports the existence of mechanisms
      that direct processes such as gene expression in the differentiation of stem
      cells. Ultimately, cells feel the difference between stiff or soft and thick or
      thin surroundings, regardless of whether or not they are of royal descent.

PMID- 20130140
TI  - Three-dimensional organization of promyelocytic leukemia nuclear bodies.
AB  - Promyelocytic leukemia nuclear bodies (PML-NBs) are mobile subnuclear organelles
      formed by PML and Sp100 protein. They have been reported to have a role in
      transcription, DNA replication and repair, telomere lengthening, cell cycle
      control and tumor suppression. We have conducted high-resolution 4Pi fluorescence
      laser-scanning microscopy studies complemented with correlative electron
      microscopy and investigations of the accessibility of the PML-NB subcompartment.
      During interphase PML-NBs adopt a spherical organization characterized by the
      assembly of PML and Sp100 proteins into patches within a 50- to 100-nm-thick
      shell. This spherical shell of PML and Sp100 imposes little constraint to the
      exchange of components between the PML-NB interior and the nucleoplasm. Post
      translational SUMO modifications, telomere repeats and heterochromatin protein 1
      were found to localize in characteristic patterns with respect to PML and Sp100.
      From our findings, we derived a model that explains how the three-dimensional
      organization of PML-NBs serves to concentrate different biological activities
      while allowing for an efficient exchange of components.

PMID- 20130141
TI  - Dynamic organisation of prolactin gene expression in living pituitary tissue.
AB  - Gene expression in living cells is highly dynamic, but temporal patterns of gene
      expression in intact tissues are largely unknown. The mammalian pituitary gland
      comprises several intermingled cell types, organised as interdigitated networks
      that interact functionally to generate co-ordinated hormone secretion. Live-cell
      imaging was used to quantify patterns of reporter gene expression in dispersed
      lactotrophic cells or intact pituitary tissue from bacterial artificial
      chromosome (BAC) transgenic rats in which a large prolactin genomic fragment
      directed expression of luciferase or destabilised enhanced green fluorescent
      protein (d2EGFP). Prolactin promoter activity in transgenic pituitaries varied
      with time across different regions of the gland. Although amplitude of
      transcriptional responses differed, all regions of the gland displayed similar
      overall patterns of reporter gene expression over a 50-hour period, implying
      overall co-ordination of cellular behaviour. By contrast, enzymatically dispersed
      pituitary cell cultures showed unsynchronised fluctuations of promoter activity
      amongst different cells, suggesting that transcriptional patterns were
      constrained by tissue architecture. Short-term, high resolution, single cell
      analyses in prolactin-d2EGFP transgenic pituitary slice preparations showed
      varying transcriptional patterns with little correlation between adjacent cells.
      Together, these data suggest that pituitary tissue comprises a series of cell
      ensembles, which individually display a variety of patterns of short-term
      stochastic behaviour, but together yield long-range and long-term coordinated
      behaviour.

PMID- 20130142
TI  - Swine-origin influenza virus and the 2009 pandemic.

PMID- 20130143
TI  - Identifying clinical phenotypes of asthma: steps in the right direction.

PMID- 20130144
TI  - A second chance. Setting a protective ozone standard.

PMID- 20130145
TI  - Influenza A/H1N1_09: Australia and New Zealand's winter of discontent.
AB  - Influenza A/H1N1_09 emerged in Mexico at the end of the Northern Hemisphere
      winter. Within weeks, the focus shifted to the Southern Hemisphere as the
      introduction of the novel virus coincided with the beginning of the influenza
      season. Intensive public health and health services planning had occurred in
      Australia and New Zealand as preparation for an influenza pandemic before 2009.
      However, this first pandemic wave was quite different to what had been expected.
      Key elements of the pandemic and response are outlined from the perspective of
      clinicians working at the frontline of patient care. In particular, they examine
      why past influenza pandemics and recent history are poor predictors of the
      current pandemic, the discordance between potential for transmission and disease
      severity, the broad clinical spectrum of H1N1_09 infection, clinical and health
      service management issues, and the relationship between health care and
      government policy. Finally, they address the need for the respiratory community
      to show leadership in times of crisis. Lessons learned in Australia and New
      Zealand during 2009 have important messages for similarly resourced countries in
      the Northern Hemisphere in the coming months as they face their own influenza
      season.

PMID- 20130147
TI  - Duration of ICU delirium, severity of the underlying disease, and mortality.

PMID- 20130146
TI  - An official research policy statement of the American Thoracic Society/European
      Respiratory Society: standards for quantitative assessment of lung structure.

PMID- 20130148
TI  - Molecular Th2 phenotypes of asthma: new biomarker or NO?

PMID- 20130149
TI  - Initial preference for drinking goal in the treatment of alcohol problems: I.
      Baseline differences between abstinence and non-abstinence groups.
AB  - AIMS: To compare baseline characteristics of clients initially preferring
      abstinence with those preferring non-abstinence at the screening stage of a
      randomized controlled trial of treatment for alcohol problems (UKATT) and to
      identify predictors of goal preference from client characteristics present before
      the preference was stated. METHODS: From discussions with clients entering the
      trial (N = 742), screeners noted whether clients were aiming for abstinence
      'probably yes' or 'probably no'. Differences between the two groups thus formed
      were explored by univariate comparisons among client characteristics recorded at
      baseline assessment and by logistic regression analysis with pre-existing
      characteristics as independent variables. RESULTS: Across all UKATT sites, 54.3%
      of clients expressed a preference for abstinence and 45.7% for non-abstinence. In
      univariate comparisons, clients preferring abstinence were significantly (P <
      0.01) more likely to: (i) be female, (ii) be unemployed, (iii) report drinking
      more heavily but less frequently, (iv) have been detoxified in the 2 weeks prior
      to assessment, (v) report more alcohol problems, (vi) be in the action stage of
      change, (vii) report greater negative expectancies of drinking, (viii) report
      greater mental and physical ill-health, (ix) report less social support for
      drinking and (x) be more confident of their ability to resist heavy drinking in
      tempting situations. In the logistic regression model, the strongest predictors
      of goal preference were gender, drinking pattern, recent detoxification and
      social support for drinking. CONCLUSION: The implications of these findings for
      service delivery are best considered in conjunction with findings from a
      companion paper reporting treatment outcomes associated with each goal
      preference.

PMID- 20130151
TI  - Editor's note. The theme of GI motility disorders.

PMID- 20130150
TI  - Initial preference for drinking goal in the treatment of alcohol problems: II.
      Treatment outcomes.
AB  - AIMS: To compare treatment outcomes between clients preferring abstinence and
      those preferring non-abstinence at the screening stage of a randomized controlled
      trial of treatment for alcohol problems (the United Kingdom Alcohol Treatment
      Trial) and to interpret any differential outcome in light of baseline differences
      between goal preference groups outlined in an accompanying paper. METHODS:
      Outcomes at 3 and 12 months' follow-up were recorded both in categorical terms
      (abstinence/non-problem drinking/much improved/somewhat improved/same/worse) and
      on continuous measures (percent days abstinent, drinks per drinking
      day/dependence score). RESULTS: Clients initially stating a preference for
      abstinence showed a better outcome than those stating a preference for non
      abstinence. This superior outcome was clearer at 3 months' follow-up but still
      evident at 12 months' follow-up. The better outcome consisted almost entirely in
      a greater frequency of abstinent days, with only a modest benefit in drinking
      intensity for goal abstainers that disappeared when baseline covariates of goal
      preference were controlled for. Type of successful outcome (abstinence/non
      problem drinking) was related to initial goal preference, with clients preferring
      abstinence more likely to obtain an abstinent outcome and those preferring non
      abstinence a non-problem drinking outcome. CONCLUSION: The client's personal
      drinking goals should be discussed in assessment at treatment entry and as a
      basis for negotiation. Clinicians should be prepared to identify and support goal
      change as an unexceptional part of the treatment process that need not jeopardize
      good outcome.

PMID- 20130152
TI  - A "gutsy move": tackling enteral feeding intolerance in critically ill patients.

PMID- 20130153
TI  - Challenges in nutrition, pressure ulcers, and wound healing.

PMID- 20130154
TI  - Altered GI motility in critically Ill patients: current understanding of
      pathophysiology, clinical impact, and diagnostic approach.
AB  - Gastrointestinal (GI) motility disturbances are common in critically ill
      patients. GI tract dysmotility has been linked to increased permeability of
      intestinal mucosa and bacterial translocation, contributing to systemic
      inflammatory response syndrome, sepsis, and multiple organ dysfunction syndrome.
      A key issue in providing nutrition to critically ill patients is intolerance of
      enteral feeding as a result of impaired GI motility. Remarkable progress has been
      made in the understanding of the regulation of GI motility in critical illness.
      Predominant motility abnormalities seen in ICU patients include antral
      hypomotility, delayed gastric emptying, and reduced migrating motor complexes.
      The diagnosis of motility disturbances can be challenging to establish in
      critically ill patients. The available tests used for detection of abnormal
      motility have major limitations in the ICU setting. Recognition of the type and
      site of intestinal motility disorder is important to guide the therapy and
      improve the outcome.

PMID- 20130155
TI  - Current and future therapeutic prokinetic therapy to improve enteral feed
      intolerance in the ICU patient.
AB  - Malnutrition is associated with poor outcomes in critically ill patients, and
      providing enteral feeding to those who cannot eat is considered best practice.
      Enteral feeding is often unsuccessful when there is delayed gastric emptying.
      Recent research has given additional insight into the mechanisms underlying
      delayed gastric emptying. Pharmacological strategies to improve the success of
      feeding include prokinetic drugs such as metoclopramide and erythromycin alone or
      in combination. When drug treatment fails, either parenteral nutrition or direct
      small intestinal feeding is indicated. Simpler methods to access the duodenum and
      distal small bowel for feed delivery are under investigation. This review
      summarizes current understanding of the mechanisms underlying enteral feeding
      intolerance in critical illness, together with the evidence for current treatment
      practices. Areas requiring further research are also described.

PMID- 20130156
TI  - Critical illness, gastrointestinal complications, and medication therapy during
      enteral feeding in critically ill adult patients.
AB  - Critically ill patients who are subjected to high stress or with severe injury
      can rapidly break down their body protein and energy stores. Unless adequate
      nutrition is provided, malnutrition and protein wasting may occur, which can
      negatively affect patient outcome. Enteral nutrition (EN) is the mainstay of
      nutrition support therapy in patients with a functional gastrointestinal (GI)
      tract who cannot take adequate oral nutrition. EN in critically ill patients
      provides the benefits of maintaining gut functionality, integrity, and immunity
      as well as decreasing infectious complications. However, the ability to provide
      timely and adequate EN to critically ill patients is often hindered by GI
      motility disorders and complications associated with EN. This paper reviews the
      GI complications and intolerances associated with EN in critically ill patients
      and provides recommendations for their prevention and treatment. It also
      addresses the role of commonly used medications in the intensive care unit and
      their impact on GI motility and EN delivery.

PMID- 20130157
TI  - Nutrition management of pressure ulcers.
AB  - Despite our knowledge of how to prevent pressure ulcers, and improvements in
      treatment, pressure ulcers remain prevalent and impose a significant burden on
      financial and labor resources in the healthcare industry. Although there is no
      known role for specific nutrients in the prevention of pressure ulcers,
      undernutrition is a risk factor, and nutrition therapy plays a crucial role in
      pressure ulcer treatment. Limitations in research make it difficult to develop
      evidence-based nutrition guidelines, so it is important that clinicians conduct a
      comprehensive assessment that includes weight and intake history, biochemical
      data, and comorbidities as well as symptoms that may affect the intake,
      absorption, or excretion of nutrients. These data, combined with clinical
      judgment, must be used to estimate energy and protein needs, considering the size
      and severity of the pressure ulcer. Micronutriture is difficult to assess; usual
      intake, comorbidities and disease symptoms must be considered in addition to
      biochemical data. Micronutrients should be replaced if depleted, but routine
      supplementation of vitamins and minerals in all pressure ulcer patients is not
      warranted.

PMID- 20130158
TI  - Understanding the role of nutrition and wound healing.
AB  - Optimal wound healing requires adequate nutrition. Nutrition deficiencies impede
      the normal processes that allow progression through stages of wound healing.
      Malnutrition has also been related to decreased wound tensile strength and
      increased infection rates. Malnourished patients can develop pressure ulcers,
      infections, and delayed wound healing that result in chronic nonhealing wounds.
      Chronic wounds are a significant cause of morbidity and mortality for many
      patients and therefore constitute a serious clinical concern. Because most
      patients with chronic skin ulcers suffer micronutrient status alterations and
      malnutrition to some degree, current nutrition therapies are aimed at correcting
      nutrition deficiencies responsible for delayed wound healing. This review
      provides current information on nutrition management for simple acute wounds and
      complex nonhealing wounds and offers some insights into innovative future
      treatments.

PMID- 20130159
TI  - Early parenteral nutrition and successful postnatal growth of premature infants.
AB  - BACKGROUND: Premature infants have uniformly demonstrated growth failure by 36
      weeks postmenstrual age. In an evaluation of care quality, the authors tested the
      hypothesis that premature infants would grow adequately when they received more
      than 50 kcal/kg per day of parenteral nutrition. METHODS: The study cohort
      consisted of 84 premature infants born at less than 30 weeks gestation. A
      computer software program was used to determine parenteral nutrition orders and
      establish a database. The database provided the nutrition and postnatal growth
      data. Successful growth was defined as weight greater than the 10th percentile
      for intrauterine growth. RESULTS: Energy intake exceeded 50 kcal/kg per day after
      the first day. The cohort weight and head circumference measurements remained
      above the 10th percentile of intrauterine growth through 36 weeks postmenstrual
      age. Infants demonstrated successful growth by remaining above the 10th
      percentile for the following: 4 of 12 (33%) with birth weights 501-750 g, 16 of
      26 (62%) with birth weights 751-1,000 g, and 16 of 25 (64%) with birth weights
      1,001-1,250 g. These differences were statistically greater than a large
      reference cohort (P < .0001). Length measurements declined below the 10th
      percentile of intrauterine growth at 36 weeks postmenstrual age. CONCLUSIONS:
      Postnatal growth failure is not an inevitable consequence of premature birth. The
      clinical evidence supports previous nutrient recommendations from the American
      Academy of Pediatrics. Promptly providing premature infants with parenteral
      nutrition, including calories greater than the basal energy requirement, can
      produce postnatal growth that remains above the 10th percentile of intrauterine
      growth.

PMID- 20130160
TI  - The state of nutrition support teams and update on current models for providing
      nutrition support therapy to patients.

PMID- 20130161
TI  - Role of complementary and alternative medicine in managing gastrointestinal
      motility disorders.

PMID- 20130162
TI  - Meat-induced joint attacks, or meat attacks the joint: rheumatism versus allergy.

PMID- 20130164
TI  - Does use of advanced information technology in commercial minimum data set
      systems improve quality of nursing home care?
AB  - Information technology (IT) has been recommended to improve the quality of health
      care. Nursing homes use very little IT, but they have been required by the
      federal government to electronically submit resident assessments (via commercial
      Minimum Data Set [MDS] software). This article examines whether use of the
      advanced IT features commonly found in commercial MDS software is associated with
      better quality of care. This study employed a national survey of US nursing home
      administrators (N = 2397) regarding the use of 12 advanced IT features in
      commercial MDS software. Overall, the effects of using advanced IT features in
      commercial MDS software on quality were highly significant (P < .01) when
      controlling for the prior years quality as well as facility characteristics.
      Although nursing homes have been slow to adopt IT, the use of the identified IT
      in MDS software packages appears to offer the promise to improve quality of care.

PMID- 20130165
TI  - Tools for building clinic-community partnerships to support chronic disease
      control and prevention.
AB  - PURPOSE: Developing partnerships among health care clinics and community
      organizations is an important strategy for increasing resources and supports for
      chronic disease care and management. Although several tools assessing partnership
      characteristics exist, tools to assess the progression from partnership
      development to the achievement of specific short-term, intermediate, and long
      term outcomes have not been developed to date. The purpose of this article is to
      introduce tools developed by the Diabetes Initiative of the Robert Wood Johnson
      Foundation to fill that gap. CONCLUSION: The Diabetes Initiative used a group
      process with program grantees to better delineate the phases of partnership
      development that contribute to the achievement of a shared long-term goal. The
      Framework for Building Clinic-Community Partnerships to Support Chronic Disease
      Control and Prevention presented in this article was developed as a result of
      this process. To apply the framework, 3 checklists were created to correspond to
      each stage of the framework. The final tools include the framework; 3 checklists
      with items to assess partnership development, agency capacity within and between
      agencies, and intermediate and long-term outcomes; and a form to facilitate
      changes to improve the partnership. Overall, these tools seek to aid partnerships
      in achieving the best possible chronic disease outcomes.

PMID- 20130166
TI  - Assessment of parent-adolescent partnership in diabetes care: a review of
      measures.
AB  - PURPOSE: To identify and evaluate psychometric properties of available measures
      to assess dimensions of parent-adolescent partnership in diabetes care, including
      parent-adolescent responsibility in diabetes management, parental monitoring,
      diabetes family conflict, and parental involvement. METHODS: A literature review
      that included searches of electronic databases from 1990 to April 2009 was
      conducted. Instruments were reviewed extracting information about aim, target
      population, and psychometric properties. RESULTS: Eight instruments were
      identified. Study samples appear to be large enough for psychometric validation
      but with a small proportion of fathers. The instruments have been designed and
      evaluated with adolescents and parents in the United States. Most of the
      instruments have adequate reliability, both for adolescents' and parents' forms.
      Regarding construct validity, factor structure of most of the instruments was
      evaluated either with exploratory factor analysis or confirmatory factor
      analysis. In addition, some measures have significant relationships with age in
      the direction expected or with other outcomes such as adherence or quality of
      life. Finally, all the reviewed studies are cross-sectional and have not yet
      addressed predictive validity or instrument responsiveness. CONCLUSIONS: Valid
      measures tapping into aspects of diabetes-related adolescent-parent partnership
      are available, but longitudinal studies are needed to determine if the
      instruments are able to detect clinically significant change (eg, impact on
      metabolic control, adherence, quality of life). Rather than develop new measures,
      refinement and further validation of existing instruments is suggested.

PMID- 20130167
TI  - Unraveling LRRK2 pathogenesis: common pathways for complex genes?

PMID- 20130168
TI  - New clues suggest distinct functional roles for M1 and M2 intrinsically
      photosensitive retinal ganglion cells.

PMID- 20130169
TI  - Genetic fate mapping reveals that the caudal ganglionic eminence produces a large
      and diverse population of superficial cortical interneurons.
AB  - By combining an inducible genetic fate mapping strategy with electrophysiological
      analysis, we have systematically characterized the populations of cortical
      GABAergic interneurons that originate from the caudal ganglionic eminence (CGE).
      Interestingly, compared with medial ganglionic eminence (MGE)-derived cortical
      interneuron populations, the initiation [embryonic day 12.5 (E12.5)] and peak
      production (E16.5) of interneurons from this embryonic structure occurs 3 d later
      in development. Moreover, unlike either pyramidal cells or MGE-derived cortical
      interneurons, CGE-derived interneurons do not integrate into the cortex in an
      inside-out manner but preferentially (75%) occupy superficial cortical layers
      independent of birthdate. In contrast to previous estimates, CGE-derived
      interneurons are both considerably greater in number (approximately 30% of all
      cortical interneurons) and diversity (comprised by at least nine distinct
      subtypes). Furthermore, we found that a large proportion of CGE-derived
      interneurons, including the neurogliaform subtype, express the glycoprotein
      Reelin. In fact, most CGE-derived cortical interneurons express either Reelin or
      vasoactive intestinal polypeptide. Thus, in conjunction with previous studies, we
      have now determined the spatial and temporal origins of the vast majority of
      cortical interneuron subtypes.

PMID- 20130170
TI  - Expression of COUP-TFII nuclear receptor in restricted GABAergic neuronal
      populations in the adult rat hippocampus.
AB  - The COUP-TFII nuclear receptor, also known as NR2F2, is expressed in the
      developing ventral telencephalon and modulates the tangential migration of a set
      of subpallial neuronal progenitors during forebrain development. Little
      information is available about its expression patterns in the adult brain. We
      have identified the cell populations expressing COUP-TFII and the contribution of
      some of them to network activity in vivo. Expression of COUP-TFII by hippocampal
      pyramidal and dentate granule cells, as well as neurons in the neocortex, formed
      a gradient increasing from undetectable in the dorsal to very strong in the
      ventral sectors. In the dorsal hippocampal CA1 area, COUP-TFII was restricted to
      GABAergic interneurons and expressed in several, largely nonoverlapping neuronal
      populations. Immunoreactivity was present in calretinin-, neuronal nitric oxide
      synthase-, and reelin-expressing cells, as well as in subsets of cholecystokinin-
      or calbindin-expressing or radiatum-retrohippocampally projecting GABAergic
      cells, but not in parvalbumin- and/or somatostatin-expressing interneurons. In
      vivo recording and juxtacellular labeling of COUP-TFII-expressing cells revealed
      neurogliaform cells, basket cells in stratum radiatum and tachykinin-expressing
      radiatum dentate innervating interneurons, identified by their axodendritic
      distributions. They showed cell type-selective phase-locked firing to the theta
      rhythm but no activation during sharp wave/ripple oscillations. These basket
      cells in stratum radiatum and neurogliaform cells fired at the peak of theta
      oscillations detected extracellularly in stratum pyramidale, unlike previously
      reported ivy cells, which fired at the trough. The characterization of COUP-TFII
      expressing neurons suggests that this developmentally important transcription
      factor plays cell type-specific role(s) in the adult hippocampus.

PMID- 20130171
TI  - Dopamine and memory: modulation of the persistence of memory for novel
      hippocampal NMDA receptor-dependent paired associates.
AB  - Three experiments investigated the role in memory processing of dopamine (DA)
      afferents to the hippocampus (HPC) that arise from the ventral tegmental area.
      One hypothesis is that D(1)/D(5) receptor activation in HPC is necessary for the
      encoding of novel, episodic-like information; the other is that DA activation
      ensures the greater temporal persistence of transient hippocampal memory traces.
      Rats (n = 35) were trained, in separate experiments using an episodic-like memory
      task, to learn six paired associates (PAs) in an "event arena" involving a
      repeated association between specific flavors of food and locations in space.
      After 6 weeks of training, rats had learned a "schema" such that two new paired
      associates could be acquired in a single trial in one session (episodic-like
      memory). We show that encoding of novel PAs is sensitive to intrahippocampal
      microinfusion of the NMDA antagonist d-AP-5. Experiment 1 established that
      intrahippocampal infusion of the D(1)/D(5) dopaminergic antagonist SCH23390 [R(+)
      7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrochloride] before encoding of new PAs caused impaired memory 24 h later but
      that SCH23390 had no effect on the later memory of previously established PAs.
      Experiment 2 established that SCH23390 modulated the persistence of new memories
      over time (30 min vs 24 h) rather than affecting initial encoding. Experiment 3
      revealed that the impact of SCH23390 was not mediated by state dependence nor had
      an effect on memory retrieval. These findings support the second hypothesis and
      establish that persistent, long-term memory of rapid, hippocampal-mediated
      acquisition of new paired associates requires activation of D(1)/D(5) receptors
      in HPC at or around the time of encoding.

PMID- 20130172
TI  - Network dynamics during development of pharmacologically induced epileptic
      seizures in rats in vivo.
AB  - In epilepsy, the cortical network fluctuates between the asymptomatic interictal
      state and the symptomatic ictal state of seizures. Despite their importance, the
      network dynamics responsible for the transition between the interictal and ictal
      states are largely unknown. Here we used multielectrode single-unit recordings
      from the hippocampus to investigate the network dynamics during the development
      of seizures evoked by various chemoconvulsants in vivo. In these experiments, we
      detected a typical network dynamics signature that preceded seizure initiation.
      The preictal state preceding pilocarpine-, kainate-, and picrotoxin-induced
      seizures was characterized by biphasic network dynamics composed of an early
      desynchronization phase in which the tendency of neurons to fire correlated
      action potentials decreased, followed by a late resynchronization phase in which
      the activity and synchronization of the network gradually increased. This
      biphasic network dynamics preceded the initiation both of the initial seizure and
      of recurrent spontaneous seizures that followed. During seizures, firing of
      individual neurons and interneuronal synchronization further increased. These
      findings advance our understanding of the network dynamics leading to seizure
      initiation and may in future help in the development of novel seizure prediction
      algorithms.

PMID- 20130173
TI  - Cognitive loss in zinc transporter-3 knock-out mice: a phenocopy for the synaptic
      and memory deficits of Alzheimer's disease?
AB  - Zinc transporter-3 (ZnT3) protein controls synaptic vesicular Zn(2+) levels,
      which is predicted to regulate normal cognitive function. Surprisingly, previous
      studies found that 6- to 10-week-old ZnT3 knock-out (KO) mice did not show
      impairment in the Morris water maze. We hypothesized that older ZnT3 KO animals
      would display a cognitive phenotype. Here, we report that ZnT3 KO mice exhibit
      age-dependent deficits in learning and memory that are manifest at 6 months but
      not at 3 months of age. These deficits are associated with significant
      alterations in key hippocampal proteins involved in learning and memory, as
      assessed by Western blot. These include decreased levels of the presynaptic
      protein SNAP25 (-46%; p < 0.01); the postsynaptic protein PSD95 (-37%; p < 0.01);
      the glutamate receptors AMPAR (-34%; p < 0.01), NMDAR2a (-64%; p < 0.001), and
      NMDAR2b (-49%; p < 0.05); the surrogate marker of neurogenesis doublecortin (
      31%; p < 0.001); and elements of the BDNF pathway, pro-BDNF (-30%; p < 0.05) and
      TrkB (-22%; p < 0.01). In addition, there is a concomitant decrease in neuronal
      spine density (-6%; p < 0.05). We also found that cortical ZnT3 levels fall with
      age in wild-type mice (-50%; p < 0.01) in healthy older humans (ages, 48-91
      years; r(2) = 0.47; p = 0.00019) and particularly in Alzheimer's disease (AD) (
      36%; p < 0.0001). Thus, age-dependent loss of transsynaptic Zn(2+) movement leads
      to cognitive loss, and since extracellular beta-amyloid is aggregated by and
      traps this pool of Zn(2+), the genetic ablation of ZnT3 may represent a phenocopy
      for the synaptic and memory deficits of AD.

PMID- 20130174
TI  - ERK1/2 mitogen-activated protein kinase phosphorylates sodium channel Na(v)1.7
      and alters its gating properties.
AB  - Na(v)1.7 sodium channels can amplify weak stimuli in neurons and act as threshold
      channels for firing action potentials. Neurotrophic factors and pro-nociceptive
      cytokines that are released during development and under pathological conditions
      activate mitogen-activated protein kinases (MAPKs). Previous studies have shown
      that MAPKs can transduce developmental or pathological signals by regulating
      transcription factors that initiate a gene expression response, a long-term
      effect, and directly modulate neuronal ion channels including sodium channels,
      thus acutely regulating dorsal root ganglion (DRG) neuron excitability. For
      example, neurotrophic growth factor activates (phosphorylates) ERK1/2 MAPK
      (pERK1/2) in DRG neurons, an effect that has been implicated in injury-induced
      hyperalgesia. However, the acute effects of pERK1/2 on sodium channels are not
      known. We have shown previously that activated p38 MAPK (pp38) directly
      phosphorylates Na(v)1.6 and Na(v)1.8 sodium channels and regulates their current
      densities without altering their gating properties. We now report that acute
      inhibition of pERK1/2 regulates resting membrane potential and firing properties
      of DRG neurons. We also show that pERK1 phosphorylates specific residues within
      L1 of Na(v)1.7, inhibition of pERK1/2 causes a depolarizing shift of activation
      and fast inactivation of Na(v)1.7 without altering current density, and mutation
      of these L1 phosphoacceptor sites abrogates the effect of pERK1/2 on this
      channel. Together, these data are consistent with direct phosphorylation and
      modulation of Na(v)1.7 by pERK1/2, which unlike the modulation of Na(v)1.6 and
      Na(v)1.8 by pp38, regulates gating properties of this channel but not its current
      density and contributes to the effects of MAPKs on DRG neuron excitability.

PMID- 20130175
TI  - Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor
      protein in the absence of nicastrin.
AB  - Gamma-secretase is a multiprotein, intramembrane-cleaving protease with a growing
      list of protein substrates, including the Notch receptors and the amyloid
      precursor protein. The four components of gamma-secretase complex--presenilin
      (PS), nicastrin (NCT), Pen2, and Aph1--are all thought to be essential for
      activity. The catalytic domain resides within PS proteins, NCT has been suggested
      to be critical for substrate recognition, and the contributions of Pen2 and Aph1
      remain unclear. The role of NCT has been challenged recently by the observation
      that a critical residue (E332) in NCT, which had been thought to be essential for
      gamma-secretase activity, is instead involved in complex maturation. Here, we
      report that NCT is dispensable for gamma-secretase activity. NCT-independent
      gamma-secretase activity can be detected in two independent NCT-deficient mouse
      embryonic fibroblast lines and blocked by the gamma-secretase inhibitors N-[N
      (3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester and L-685,458.
      This catalytic activity requires prior ectodomain shedding of the substrate and
      can cleave ligand-activated endogenous Notch receptors, indicating presence of
      this activity at the plasma membrane. Small interfering RNA knockdown experiments
      demonstrated that NCT-independent gamma-secretase activity requires the presence
      of PS1, Pen2, and Aph1a but can tolerate knockdown of PS2 or Aph1b. We conclude
      that a PS1/Pen2/Aph1a trimeric complex is an active enzyme, displaying
      biochemical properties similar to those of gamma-secretase and roughly 50% of its
      activity when normalized to PS1 N-terminal fragment levels. This PS1/Pen2/Aph1a
      complex, however, is highly unstable. Thus, NCT acts to stabilize gamma-secretase
      but is not required for substrate recognition.

PMID- 20130176
TI  - Synergistic effects of transplanted adult neural stem/progenitor cells,
      chondroitinase, and growth factors promote functional repair and plasticity of
      the chronically injured spinal cord.
AB  - The transplantation of neural stem/progenitor cells (NPCs) is a promising
      therapeutic strategy for spinal cord injury (SCI). However, to date NPC
      transplantation has exhibited only limited success in the treatment of chronic
      SCI. Here, we show that chondroitin sulfate proteoglycans (CSPGs) in the glial
      scar around the site of chronic SCI negatively influence the long-term survival
      and integration of transplanted NPCs and their therapeutic potential for
      promoting functional repair and plasticity. We targeted CSPGs in the chronically
      injured spinal cord by sustained infusion of chondroitinase ABC (ChABC). One week
      later, the same rats were treated with transplants of NPCs and transient infusion
      of growth factors, EGF, bFGF, and PDGF-AA. We demonstrate that perturbing CSPGs
      dramatically optimizes NPC transplantation in chronic SCI. Engrafted NPCs
      successfully integrate and extensively migrate within the host spinal cord and
      principally differentiate into oligodendrocytes. Furthermore, this combined
      strategy promoted the axonal integrity and plasticity of the corticospinal tract
      and enhanced the plasticity of descending serotonergic pathways. These
      neuroanatomical changes were also associated with significantly improved
      neurobehavioral recovery after chronic SCI. Importantly, this strategy did not
      enhance the aberrant synaptic connectivity of pain afferents, nor did it
      exacerbate posttraumatic neuropathic pain. For the first time, we demonstrate key
      biological and functional benefits for the combined use of ChABC, growth factors,
      and NPCs to repair the chronically injured spinal cord. These findings could
      potentially bring us closer to the application of NPCs for patients suffering
      from chronic SCI or other conditions characterized by the formation of a glial
      scar.

PMID- 20130177
TI  - Role of afferents in the differentiation of bipolar cells in the mouse retina.
AB  - To establish dendritic arbors that integrate properly into a neural circuit,
      neurons must rely on cues from the local environment. The neurons presynaptic to
      these arbors, the afferents, are one potential source of these cues, but the
      particular dendritic features they regulate remain unclear. Retinal bipolar cells
      can be classified by the type of photoreceptor, cone or rod, forming synaptic
      contacts with their dendrites, suggesting a potential role of these afferents in
      shaping the bipolar cell dendritic arbor. In the present investigation, the role
      of photoreceptors in directing the differentiation of bipolar cells has been
      studied using two genetically modified "coneless" and "conefull" mice. Single
      cone (Type 7/CB4a) and rod bipolar cells were labeled with DiI to reveal the
      entire dendritic arbor and subsequently analyzed for several morphological
      features. For both cone and rod bipolar cells, the dendritic field area, number
      of dendritic terminals, and stratification of terminals in the outer plexiform
      layer were comparable among coneless, conefull, and wild-type retinas, and the
      overall morphological appearance of each type of cell was essentially conserved,
      indicating an independence from afferent specification. The presence of normal
      afferents was, however, found to be critical for the proper spatial distribution
      of dendritic terminals, exhibiting a clustered distribution for the cone bipolar
      cells and a dispersed distribution for the rod bipolar cells. These results
      demonstrate a selectivity in the afferent dependency of bipolar cell
      differentiation, their basic morphogenetic plan commanded cell intrinsically, and
      their fine terminal connectivity directed by the afferents themselves.

PMID- 20130178
TI  - Model calcium sensors for network homeostasis: sensor and readout parameter
      analysis from a database of model neuronal networks.
AB  - In activity-dependent homeostatic regulation (ADHR) of neuronal and network
      properties, the intracellular Ca(2+) concentration is a good candidate for
      sensing activity levels because it is correlated with the electrical activity of
      the cell. Previous ADHR models, developed with abstract activity sensors for
      model pyloric neurons and networks of the crustacean stomatogastric ganglion,
      showed that functional activity can be maintained by a regulation mechanism that
      senses activity levels solely from Ca(2+). At the same time, several
      intracellular pathways have been discovered for Ca(2+)-dependent regulation of
      ion channels. To generate testable predictions for dynamics of these signaling
      pathways, we undertook a parameter study of model Ca(2+) sensors across thousands
      of model pyloric networks. We found that an optimal regulation signal can be
      generated for 86% of model networks with a sensing mechanism that activates with
      a time constant of 1 ms and that inactivates within 1 s. The sensor performed
      robustly around this optimal point and did not need to be specific to the role of
      the cell. When multiple sensors with different time constants were used, coverage
      extended to 88% of the networks. Without changing the sensors, it extended to 95%
      of the networks by letting the sensors affect the readout nonlinearly. Specific
      to this pyloric network model, the sensor of the follower pyloric constrictor
      cell was more informative than the pacemaker anterior burster cell for producing
      a regulatory signal. Conversely, a global signal indicating network activity that
      was generated by summing the sensors in individual cells was less informative for
      regulation.

PMID- 20130179
TI  - Nitric oxide acts as a volume transmitter to modulate electrical properties of
      spontaneously firing neurons via apamin-sensitive potassium channels.
AB  - Nitric oxide (NO) is a radical and a gas, properties that allow NO to diffuse
      through membranes and potentially enable it to function as a "volume messenger."
      This study had two goals: first, to investigate the mechanisms by which NO
      functions as a modulator of neuronal excitability, and second, to compare NO
      effects produced by NO release from chemical NO donors with those elicited by
      physiological NO release from single neurons. We demonstrate that NO depolarizes
      the membrane potential of B5 neurons of the mollusk Helisoma trivolvis, initially
      increasing their firing rate and later causing neuronal silencing. Both effects
      of NO were mediated by inhibition of Ca-activated iberiotoxin- and apamin
      sensitive K channels, but only inhibition of apamin-sensitive K channels fully
      mimicked all effects of NO on firing activity, suggesting that the majority of
      electrical effects of NO are mediated via inhibition of apamin-sensitive K
      channels. We further show that single neurons release sufficient amounts of NO to
      affect the electrical activity of B5 neurons located nearby. These effects are
      similar to NO release from the chemical NO donor NOC-7 [3-(2-hydroxy-1-methyl-2
      nitrosohydazino)-N-methyl-1-propyanamine], validating the use of NO donors in
      studies of neuronal excitability. Together with previous findings demonstrating a
      role for NO in neurite outgrowth and growth cone motility, the results suggest
      that NO has the potential to shape the development of the nervous system by
      modulating both electrical activity and neurite outgrowth in neurons located in
      the vicinity of NO-producing cells, supporting the notion of NO functioning as a
      volume messenger.

PMID- 20130180
TI  - Anti-glucocorticoid gene therapy reverses the impairing effects of elevated
      corticosterone on spatial memory, hippocampal neuronal excitability, and synaptic
      plasticity.
AB  - Moderate release of the major stress hormones, glucocorticoids (GCs), improves
      hippocampal function and memory. In contrast, excessive or prolonged elevations
      produce impairments. Enzymatic degradation and reformation of GCs help to
      maintain optimal levels within target tissues, including the brain. We
      hypothesized that expressing a GC-degrading enzyme in hippocampal neurons would
      attenuate the negative impact of an excessive elevation in GC levels on synaptic
      physiology and spatial memory. We tested this by expressing 11-beta
      hydroxysteroid dehydrogenase (type II) in dentate gyrus granule cells during a 3
      d GC treatment followed by examination of synaptic responses in hippocampal
      slices or spatial performance in the Morris water maze. In adrenalectomized rats
      with basal GC replacement, additional GC treatments for 3 d reduced synaptic
      strength and promoted the expression of long-term depression at medial perforant
      path synapses, increased granule cell and CA1 pyramidal cell excitability, and
      impaired spatial reference memory (without influencing learning). Expression of
      11-beta-hydroxysteroid dehydrogenase (type II), mostly in mature dentate gyrus
      granule cells, reversed the effects of high GC levels on granule cell and
      pyramidal cell excitability, perforant path synaptic plasticity, and spatial
      memory. These data demonstrate the ability of neuroprotective gene expression
      limited to a specific cell population to both locally and trans-synaptically
      offset neurophysiological disruptions produced by prolonged increases in
      circulating stress hormones. This report supplies the first physiological
      explanation for previously demonstrated cognitive sparing by anti-stress gene
      therapy approaches and lends additional insight into the hippocampal processes
      that are important for memory.

PMID- 20130181
TI  - Contextual novelty changes reward representations in the striatum.
AB  - Reward representation in ventral striatum is boosted by perceptual novelty,
      although the mechanism of this effect remains elusive. Animal studies indicate a
      functional loop (Lisman and Grace, 2005) that includes hippocampus, ventral
      striatum, and midbrain as being important in regulating salience attribution
      within the context of novel stimuli. According to this model, reward responses in
      ventral striatum or midbrain should be enhanced in the context of novelty even if
      reward and novelty constitute unrelated, independent events. Using fMRI, we show
      that trials with reward-predictive cues and subsequent outcomes elicit higher
      responses in the striatum if preceded by an unrelated novel picture, indicating
      that reward representation is enhanced in the context of novelty. Notably, this
      effect was observed solely when reward occurrence, and hence reward-related
      salience, was low. These findings support a view that contextual novelty enhances
      neural responses underlying reward representation in the striatum and concur with
      the effects of novelty processing as predicted by the model of Lisman and Grace
      (2005).

PMID- 20130182
TI  - Global inhibition and stimulus competition in the owl optic tectum.
AB  - Stimulus selection for gaze and spatial attention involves competition among
      stimuli across sensory modalities and across all of space. We demonstrate that
      such cross-modal, global competition takes place in the intermediate and deep
      layers of the optic tectum, a structure known to be involved in gaze control and
      attention. A variety of either visual or auditory stimuli located anywhere
      outside of a neuron's receptive field (RF) were shown to suppress or completely
      eliminate responses to a visual stimulus located inside the RF in nitrous oxide
      sedated owls. The essential mechanism underlying this stimulus competition is
      global, divisive inhibition. Unlike the effect of the classical inhibitory
      surround, which decreases with distance from the RF center and shapes neuronal
      responses to individual stimuli, global inhibition acts across the entirety of
      space and modulates responses primarily in the context of multiple stimuli.
      Whereas the source of this global inhibition is as yet unknown, our data indicate
      that different networks mediate the classical surround and global inhibition. We
      hypothesize that this global, cross-modal inhibition, which acts automatically in
      a bottom-up manner even in sedated animals, is critical to the creation of a map
      of stimulus salience in the optic tectum.

PMID- 20130183
TI  - Global deprivation of brain-derived neurotrophic factor in the CNS reveals an
      area-specific requirement for dendritic growth.
AB  - Although brain-derived neurotrophic factor (BDNF) is linked with an increasing
      number of conditions causing brain dysfunction, its role in the postnatal CNS has
      remained difficult to assess. This is because the bdnf-null mutation causes the
      death of the animals before BDNF levels have reached adult levels. In addition,
      the anterograde axonal transport of BDNF complicates the interpretation of area
      specific gene deletion. The present study describes the generation of a new
      conditional mouse mutant essentially lacking BDNF throughout the CNS. It shows
      that BDNF is not essential for prolonged postnatal survival, but that the
      behavior of such mutant animals is markedly altered. It also reveals that BDNF is
      not a major survival factor for most CNS neurons and for myelination of their
      axons. However, it is required for the postnatal growth of the striatum, and
      single-cell analyses revealed a marked decreased in dendritic complexity and
      spine density. In contrast, BDNF is dispensable for the growth of the hippocampus
      and only minimal changes were observed in the dendrites of CA1 pyramidal neurons
      in mutant animals. Spine density remained unchanged, whereas the proportion of
      the mushroom-type spine was moderately decreased. In line with these in vivo
      observations, we found that BDNF markedly promotes the growth of cultured
      striatal neurons and of their dendrites, but not of those of hippocampal neurons,
      suggesting that the differential responsiveness to BDNF is part of a neuron
      intrinsic program.

PMID- 20130184
TI  - In the developing rat hippocampus, endogenous activation of presynaptic kainate
      receptors reduces GABA release from mossy fiber terminals.
AB  - Presynaptic kainate receptors regulate synaptic transmission in several brain
      areas but are not known to have this action at immature mossy fiber (MF)
      terminals, which during the first week of postnatal life release GABA, which
      exerts into targeted cells a depolarizing and excitatory action. Here, we report
      that, during the first week of postnatal life, endogenous activation of GluK1
      receptors by glutamate present in the extracellular space severely depresses MF
      mediated GABAergic currents [GABA(A)-mediated postsynaptic currents (GPSCs)].
      Activation of GluK1 receptors was prevented by treating the slices with enzymatic
      glutamate scavengers that enhanced the clearance of glutamate from the
      extracellular space. The depressant effect of GluK1 on MF-GPSCs was mediated by a
      metabotropic process sensitive to pertussis toxin. In the presence of U73122 (1
      [6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5
      dione), a selective inhibitor of phospholipase C, along the transduction pathway
      downstream to G-protein, GluK1 activation increased the probability of GABA
      release, thus unveiling the ionotropic action of this receptor. In line with this
      type of action, we found that GluK1 enhanced MF excitability by directly
      depolarizing MF terminals via calcium-permeable cation channels. Furthermore,
      GluK1 dynamically regulated the direction of spike time-dependent plasticity
      occurring by pairing MF stimulation with postsynaptic spiking and switched spike
      time-dependent potentiation into depression. The GluK1-induced depression of MF
      GPSCs would prevent excessive activation of the CA3 associative network by the
      excitatory action of GABA and the emergence of seizures in the immature brain.

PMID- 20130185
TI  - Single-unit activity in piriform cortex during slow-wave state is shaped by
      recent odor experience.
AB  - Memory and its underlying neural plasticity play important roles in sensory
      discrimination and cortical pattern recognition in olfaction. Given the reported
      function of slow-wave sleep states in neocortical and hippocampal memory
      consolidation, we hypothesized that activity during slow-wave states within the
      piriform cortex may be shaped by recent olfactory experience. Rats were
      anesthetized with urethane and allowed to spontaneously shift between slow-wave
      and fast-wave states as recorded in local field potentials within the anterior
      piriform cortex. Single-unit activity of piriform cortical layer II/III neurons
      was recorded simultaneously. The results suggest that piriform cortical activity
      during slow-wave states is shaped by recent (several minutes) odor experience.
      The temporal structure of single-unit activity during slow waves was modified if
      the animal had been stimulated with an odor within the receptive field of that
      cell. If no odor had been delivered, the activity of the cell during slow-wave
      activity was stable across the two periods. The results demonstrate that piriform
      cortical activity during slow-wave state is shaped by recent odor experience,
      which could contribute to odor memory consolidation.

PMID- 20130186
TI  - The N-glycanase png-1 acts to limit axon branching during organ formation in
      Caenorhabditis elegans.
AB  - Peptide:N-glycanases (PNGases) are cytoplasmic de-N-glycosylation enzymes that
      have been shown in cultured cells to facilitate the degradation of misfolded
      glycoproteins during endoplasmic reticulum-associated degradation and in the
      processing of major histocompatibility complex class I antigens for proper cell
      surface presentation. The gene encoding PNGase activity was initially described
      in budding yeast (Png1p) and shown to be highly conserved from yeast to humans,
      but physiological roles in higher organisms have not been elucidated. Here we
      describe peripheral nervous system defects associated with the first loss-of
      function mutations in an animal PNGase. Mutations in png-1, the Caenorhabditis
      elegans PNGase ortholog, result in an increase in axon branching during
      morphogenesis of the vulval egg-laying organ and egg-laying behavior changes.
      Neuronal defects include an increase in the branched morphology of the VC4 and
      VC5 egg-laying neurons as well as inappropriate branches from axons that run
      adjacent to the vulva but would normally remain unbranched. We show that png-1 is
      widely expressed and can act from both neurons and epithelial cells to restrict
      axon branching. A deletion allele of the DNA repair gene rad-23, orthologs of
      which are known to physically interact with PNGases in yeast and mammals,
      displays similar axon branching defects and genetic interactions with png-1. In
      summary, our analysis reveals a novel developmental role for a PNGase and Rad-23
      in the regulation of neuronal branching during organ innervation.

PMID- 20130187
TI  - Distinct representations and theta dynamics in dorsal and ventral hippocampus.
AB  - Although anatomical, lesion, and imaging studies of the hippocampus indicate
      qualitatively different information processing along its septo-temporal axis,
      physiological mechanisms supporting such distinction are missing. We found
      fundamental differences between the dorsal (dCA3) and the ventral-most parts
      (vCA3) of the hippocampus in both environmental representation and temporal
      dynamics. Discrete place fields of dCA3 neurons evenly covered all parts of the
      testing environments. In contrast, vCA3 neurons (1) rarely showed continuous two
      dimensional place fields, (2) differentiated open and closed arms of a radial
      maze, and (3) discharged similar firing patterns with respect to the goals, both
      on multiple arms of a radial maze and during opposite journeys in a zigzag maze.
      In addition, theta power and the fraction of theta-rhythmic neurons were
      substantially reduced in the ventral compared with dorsal hippocampus. We
      hypothesize that the spatial representation in the septo-temporal axis of the
      hippocampus is progressively decreased. This change is paralleled with a
      reduction of theta rhythm and an increased representation of nonspatial
      information.

PMID- 20130188
TI  - Enhanced striatal dopamine transmission and motor performance with LRRK2
      overexpression in mice is eliminated by familial Parkinson's disease mutation
      G2019S.
AB  - PARK8/LRRK2 (leucine-rich repeat kinase 2) was recently identified as a causative
      gene for autosomal dominant Parkinson's disease (PD), with LRRK2 mutation G2019S
      linked to the most frequent familial form of PD. Emerging in vitro evidence
      indicates that aberrant enzymatic activity of LRRK2 protein carrying this
      mutation can cause neurotoxicity. However, the physiological and
      pathophysiological functions of LRRK2 in vivo remain elusive. Here we
      characterize two bacterial artificial chromosome (BAC) transgenic mouse strains
      overexpressing LRRK2 wild-type (Wt) or mutant G2019S. Transgenic LRRK2-Wt mice
      had elevated striatal dopamine (DA) release with unaltered DA uptake or tissue
      content. Consistent with this result, LRRK2-Wt mice were hyperactive and showed
      enhanced performance in motor function tests. These results suggest a role for
      LRRK2 in striatal DA transmission and the consequent motor function. In contrast,
      LRRK2-G2019S mice showed an age-dependent decrease in striatal DA content, as
      well as decreased striatal DA release and uptake. Despite increased brain kinase
      activity, LRRK2-G2019S overexpression was not associated with loss of DAergic
      neurons in substantia nigra or degeneration of nigrostriatal terminals at 12
      months. Our results thus reveal a pivotal role for LRRK2 in regulating striatal
      DA transmission and consequent control of motor function. The PD-associated
      mutation G2019S may exert pathogenic effects by impairing these functions of
      LRRK2. Our LRRK2 BAC transgenic mice, therefore, could provide a useful model for
      understanding early PD pathological events.

PMID- 20130189
TI  - A role for the ubiquitin-proteasome system in activity-dependent presynaptic
      silencing.
AB  - Chronic changes in electrical excitability profoundly affect synaptic
      transmission throughout the lifetime of a neuron. We have previously explored
      persistent presynaptic silencing, a form of synaptic depression at glutamate
      synapses produced by ongoing neuronal activity and by strong depolarization. Here
      we investigate the involvement of the ubiquitin-proteasome system (UPS) in the
      modulation of presynaptic function. We found that proteasome inhibition prevented
      the induction of persistent presynaptic silencing. Specifically, application of
      the proteasome inhibitor MG-132 (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal)
      prevented decreases in the size of the readily releasable pool of vesicles and in
      the percentage of active synapses. Presynaptic silencing was accompanied by
      decreases in levels of the priming proteins Munc13-1 and Rim1. Importantly,
      overexpression of Rim1alpha prevented the induction of persistent presynaptic
      silencing. Furthermore, strong depolarization itself increased proteasome
      enzymatic activity measured in cell lysates. These results suggest that
      modulation of the UPS by electrical activity contributes to persistent
      presynaptic silencing by promoting the degradation of key presynaptic proteins.

PMID- 20130190
TI  - Upper airway dysfunction of Tau-P301L mice correlates with tauopathy in midbrain
      and ponto-medullary brainstem nuclei.
AB  - Tauopathy comprises hyperphosphorylation of the microtubule-associated protein
      tau, causing intracellular aggregation and accumulation as neurofibrillary
      tangles and neuropil treads. Some primary tauopathies are linked to mutations in
      the MAPT gene coding for protein tau, but most are sporadic with unknown causes.
      Also, in Alzheimer's disease, the most frequent secondary tauopathy, neither the
      cause nor the pathological mechanisms and repercussions are understood.
      Transgenic mice expressing mutant Tau-P301L suffer cognitive and motor defects
      and die prematurely from unknown causes. Here, in situ electrophysiology in
      symptomatic Tau-P301L mice (7-8 months of age) revealed reduced postinspiratory
      discharges of laryngeal motor outputs that control laryngeal constrictor muscles.
      Under high chemical drive (hypercapnia), postinspiratory discharge was nearly
      abolished, whereas laryngeal inspiratory discharge was increased
      disproportionally. The latter may suggest a shift of postinspiratory laryngeal
      constrictor activity into inspiration. In vivo double-chamber plethysmography of
      Tau-P301L mice showed significantly reduced respiratory airflow but significantly
      increased chest movements during baseline breathing, but particularly in
      hypercapnia, confirming a significant increase in inspiratory resistive load.
      Histological analysis demonstrated hyperphosphorylated tau in brainstem nuclei,
      directly or indirectly involved in upper airway motor control (i.e., the Kolliker
      Fuse, periaqueductal gray, and intermediate reticular nuclei). In contrast, young
      Tau-P301L mice did not show breathing disorders or brainstem tauopathy.
      Consequently, in aging Tau-P301L mice, progressive upper airway dysfunction is
      linked to progressive tauopathy in identified neural circuits. Because patients
      with tauopathy suffer from upper airway dysfunction, the Tau-P301L mice can serve
      as an experimental model to study disease-specific synaptic dysfunction in well
      defined functional neural circuits.

PMID- 20130191
TI  - 12-Lipoxygenase regulates hippocampal long-term potentiation by modulating L-type
      Ca2+ channels.
AB  - Although long-term potentiation (LTP) has been intensively studied, there is
      disagreement as to which molecules mediate and modulate LTP. This is partly
      attributable to the presence of mechanistically distinct forms of LTP that are
      induced by different patterns of stimulation and that depend on distinct Ca(2+)
      sources. Here, we report a novel role for the arachidonic acid-metabolizing
      enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is
      dependent on the pattern of tetanic stimulation. We find that 12-LO activity is
      required for the induction of LTP in response to a theta burst stimulation
      protocol that depends on Ca(2+) influx through both NMDA receptors and L-type
      voltage-gated Ca(2+) channels. In contrast, LTP induced by 100 Hz tetanic
      stimulation, which requires Ca(2+) influx through NMDA receptors but not L-type
      channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing
      postsynaptic somatodendritic Ca(2+) influx through L-type channels during theta
      burst stimulation, an action exerted via 12(S)-HPETE [12(S)-hydroperoxyeicosa
      5Z,8Z,10E,14Z-tetraenoic acid], a downstream metabolite of 12-LO. These results
      help define the role of a long-disputed signaling enzyme in LTP.

PMID- 20130192
TI  - Corticofugal control of vibrissa-sensitive neurons in the interpolaris nucleus of
      the trigeminal complex.
AB  - Trigeminal sensory nuclei that give rise to ascending pathways of vibrissal
      information are heavily linked by intersubnuclear connections. This is the case,
      for instance, of the principal trigeminal nucleus, which receives strong
      inhibitory input from the caudal sector of the interpolaris subnucleus. Because
      this inhibitory input can gate the relay of sensory messages through the
      lemniscal pathway, a central issue in vibrissal physiology is how brain regions
      that project to the interpolaris control the activity of inhibitory cells. In the
      present study, we examined how corticotrigeminal neurons of the primary and
      second somatosensory cortical areas control the excitability of interpolaris
      cells. Results show that these two cortical areas exert a differential control
      over the excitability of projection cells and intersubnuclear interneurons, and
      that this control also involves the recruitment of inhibitory cells in the
      caudalis subnucleus. These results provide a basic circuitry for a mechanism of
      disinhibition through which the cerebral cortex can control the relay of sensory
      messages in the lemniscal pathway. It is proposed that top-down control of
      brainstem circuits is prompted by motor strategies, expectations, and
      motivational states of the animal.

PMID- 20130193
TI  - BMPR1a and BMPR1b signaling exert opposing effects on gliosis after spinal cord
      injury.
AB  - Astrogliosis following spinal cord injury (SCI) involves an early hypertrophic
      response that is beneficial and a subsequent formation of a dense scar. We
      investigated the role of bone morphogenetic protein (BMP) signaling in gliosis
      after SCI and find that BMPR1a and BMPR1b signaling exerts opposing effects on
      hypertrophy. Conditional ablation of BMPR1a from glial fibrillary acidic protein
      (GFAP)-expressing cells leads to defective astrocytic hypertrophy, increased
      infiltration by inflammatory cells, and reduced axon density. BMPR1b-null mice
      conversely develop "hyperactive" reactive astrocytes and consequently have
      smaller lesion volumes. The effects of ablation of either receptor are reversed
      in the double knock-out animals. These findings indicate that BMPR1a and BMPR1b
      exert directly opposing effects on the initial reactive astrocytic hypertrophy.
      Also, BMPR1b knock-out mice have an attenuated glial scar in the chronic stages
      following injury, suggesting that it has a greater role in glial scar
      progression. To elucidate the differing roles of the two receptors in astrocytes,
      we examined the effects of ablation of either receptor in serum-derived
      astrocytes in vitro. We find that the two receptors exert opposing effects on the
      posttranscriptional regulation of astrocytic microRNA-21. Further, overexpression
      of microRNA-21 in wild-type serum-derived astrocytes causes a dramatic reduction
      in cell size accompanied by reduction in GFAP levels. Hence, regulation of
      microRNA-21 by BMP signaling provides a novel mechanism for regulation of
      astrocytic size. Targeting specific BMPR subunits for therapeutic purposes may
      thus provide an approach for manipulating gliosis and enhancing functional
      outcomes after SCI.

PMID- 20130194
TI  - The "cutaneous rabbit" hopping out of the body.
AB  - Rapid sequential taps delivered first to one location and then to another on the
      skin create the somatosensory illusion that the tapping is occurring at
      intermediate locations between the actual stimulus sites, as if a small rabbit
      were hopping along the skin from the first site to the second (called the
      "cutaneous rabbit"). Previous behavioral studies have attributed this illusion to
      the early unimodal somatosensory body map. A functional magnetic resonance
      imaging study recently confirmed the association of the illusion with somatotopic
      activity in the primary somatosensory cortex. Thus, the cutaneous rabbit illusion
      has been confined to one's own body. In the present paper, however, we show that
      the cutaneous rabbit can "hop out of the body" onto an external object held by
      the subject. We delivered rapid sequential taps to the left and right index
      fingers. When the subjects held a stick such that it was laid across the tips of
      their index fingers and received the taps via the stick, they reported sensing
      the illusory taps in the space between the actual stimulus locations (i.e., along
      the stick). This suggests that the cutaneous rabbit effect involves not only the
      intrinsic somatotopic representation but also the representation of the extended
      body schema that results from body-object interactions.

PMID- 20130195
TI  - Synaptic mechanisms of direction selectivity in primary auditory cortex.
AB  - Frequency modulation (FM) is a prominent feature in animal vocalization and human
      speech. Although many neurons in the auditory cortex are known to be selective
      for FM direction, the synaptic mechanisms underlying this selectivity are not
      well understood. Previous studies of both visual and auditory neurons have
      suggested two general mechanisms for direction selectivity: (1) differential
      delays of excitatory inputs across the spatial/spectral receptive field and (2)
      spatial/spectral offset between excitatory and inhibitory inputs. In this study,
      we have examined the contributions of both mechanisms to FM direction selectivity
      in rat primary auditory cortex. The excitatory and inhibitory synaptic inputs to
      each cortical neuron were measured by in vivo whole-cell recording. The
      spectrotemporal receptive field of each type of inputs was mapped with random
      tone pips and compared with direction selectivity of the neuron measured with FM
      stimuli. We found that both the differential delay of the excitatory input and
      the spectral offset between excitation and inhibition are positively correlated
      with direction selectivity of the neuron. Thus, both synaptic mechanisms are
      likely to contribute to FM direction selectivity in the auditory cortex. Finally,
      direction selectivity measured from the spiking output is significantly stronger
      than that based on the subthreshold membrane potentials, indicating that the
      selectivity is further sharpened by the spike generation mechanism.

PMID- 20130196
TI  - Presynaptic mitochondria in functionally different motor neurons exhibit similar
      affinities for Ca2+ but exert little influence as Ca2+ buffers at nerve firing
      rates in situ.
AB  - Mitochondria accumulate within nerve terminals and support synaptic function,
      most notably through ATP production. They can also sequester Ca(2+) during nerve
      stimulation, but it is unknown whether this limits presynaptic Ca(2+) levels at
      physiological nerve firing rates. Similarly, it is unclear whether mitochondrial
      Ca(2+) sequestration differs between functionally different nerve terminals. We
      addressed these questions using a combination of synthetic and genetically
      encoded Ca(2+) indicators to examine cytosolic and mitochondrial Ca(2+) levels in
      presynaptic terminals of tonic (MN13-Ib) and phasic (MNSNb/d-Is) motor neurons in
      Drosophila, which, as we determined, fire during fictive locomotion at
      approximately 42 Hz and approximately 8 Hz, respectively. Mitochondrial Ca(2+)
      sequestration starts in both terminals at approximately 250 nM, exhibits a
      similar Ca(2+)-uptake affinity (approximately 410 nM), and does not require
      Ca(2+) release from the endoplasmic reticulum. Nonetheless, mitochondrial Ca(2+)
      uptake in type Is terminals is more responsive to low-frequency nerve stimulation
      and this is due to higher cytosolic Ca(2+) levels. Since type Ib terminals have a
      higher mitochondrial density than Is terminals, it seemed possible that greater
      mitochondrial Ca(2+) sequestration may be responsible for the lower cytosolic
      Ca(2+) levels in Ib terminals. However, genetic and pharmacological manipulations
      of mitochondrial Ca(2+) uptake did not significantly alter nerve-stimulated
      elevations in cytosolic Ca(2+) levels in either terminal type within
      physiologically relevant rates of stimulation. Our findings indicate that
      presynaptic mitochondria have a similar affinity for Ca(2+) in functionally
      different nerve terminals, but do not limit cytosolic Ca(2+) levels within the
      range of motor neuron firing rates in situ.

PMID- 20130197
TI  - Ca2+ influx through NMDA-gated channels activates ATP-sensitive K+ currents
      through a nitric oxide-cGMP pathway in subthalamic neurons.
AB  - Excessive burst firing of action potentials in subthalamic nucleus (STN) neurons
      has been correlated with the bradykinesia and rigidity seen in Parkinson's
      disease. Consequently, there is much interest in characterizing mechanisms that
      promote burst firing, such as the regulation of NMDA receptor function. Using
      whole-cell recording techniques in rat brain slices, we report that inward
      currents evoked by NMDA are greatly potentiated by ATP-sensitive K(+) (K-ATP)
      channel blocking agents in STN neurons but not in dopamine neurons in the
      substantia nigra. Moreover, we found that the ability of NMDA to evoke K-ATP
      current was blocked by inhibitors of nitric oxide synthase, guanylyl cyclase, and
      calcium/calmodulin. By altering firing patterns of STN neurons, this NMDA/K-ATP
      interaction may exert an important influence on basal ganglia output and thereby
      affect the clinical expression of Parkinson's disease.

PMID- 20130198
TI  - The cerebellum harbors a circadian oscillator involved in food anticipation.
AB  - The cerebellum participates in motor coordination as well as in numerous cerebral
      processes, including temporal discrimination. Animals can predict daily timing of
      food availability, as manifested by food-anticipatory activity under restricted
      feeding. By studying ex vivo clock gene expression by in situ hybridization and
      recording in vitro Per1-luciferase bioluminescence, we report that the cerebellum
      contains a circadian oscillator sensitive to feeding cues (i.e., whose clock gene
      oscillations are shifted in response to restricted feeding). Food-anticipatory
      activity was markedly reduced in mice injected intracerebroventricularly with an
      immunotoxin that depletes Purkinje cells (i.e., OX7-saporin). Mice bearing the
      hotfoot mutation (i.e., Grid2(ho/ho)) have impaired cerebellar circuitry and mild
      ataxic phenotype. Grid2(ho/ho) mice fed ad libitum showed regular behavioral
      rhythms and day-night variations of clock gene expression in the hypothalamus and
      cerebellum. When challenged with restricted feeding, however, Grid2(ho/ho) mice
      did not show any food-anticipatory rhythms, nor timed feeding-induced changes in
      cerebellar clock gene expression. In hypothalamic arcuate and dorsomedial nuclei,
      however, shifts in Per1 expression in response to restricted feeding were similar
      in cerebellar mutant and wild-type mice. Furthermore, plasma corticosterone and
      metabolites before mealtime did not differ between cerebellar mutant and wild
      type mice. Together, these data define a role for the cerebellum in the circadian
      timing network and indicate that the cerebellar oscillator is required for
      anticipation of mealtime.

PMID- 20130199
TI  - Neural time course of echo suppression in humans.
AB  - In reverberant environments, the brain can suppress echoes so that auditory
      perception is dominated by the primary or leading sounds. Echo suppression
      comprises at least two distinct phenomena whose neural bases are unknown: spatial
      translocation of an echo toward the primary sound, and object capture to combine
      echo and primary sounds into a single event. In an electroencephalography study,
      we presented subjects with primary-echo (leading-lagging) click pairs in virtual
      acoustic space, with interclick delay at the individual's 50% suppression
      threshold. On each trial, subjects reported both click location (one or both
      hemifields) and the number of clicks they heard (one or two). Thus, the threshold
      stimulus led to two common percepts: Suppressed and Not Suppressed. On some
      trials, a subset of subjects reported an intermediate percept, in which two
      clicks were perceived in the same hemifield as the leading click, providing a
      dissociation between spatial translocation and object capture. We conducted time
      frequency and event-related potential analyses to examine the time course of the
      neural mechanisms mediating echo suppression. Enhanced gamma band phase
      synchronization (peaking at approximately 40 Hz) specific to successful echo
      suppression was evident from 20 to 60 ms after stimulus onset. N1 latency
      provided a categorical neural marker of spatial translocation, whereas N1
      amplitude still reflected the physical presence of a second (lagging) click.
      These results provide evidence that (1) echo suppression begins early, at the
      latest when the acoustic signal first reaches cortex, and (2) the brain spatially
      translocates a perceived echo before the primary sound captures it.

PMID- 20130201
TI  - The effect of spatially inhomogeneous extracellular electric fields on neurons.
AB  - The cooperative action of neurons and glia generates electrical fields, but their
      effect on individual neurons via ephaptic interactions is mostly unknown. Here,
      we analyze the impact of spatially inhomogeneous electric fields on the membrane
      potential, the induced membrane field, and the induced current source density of
      one-dimensional cables as well as morphologically realistic neurons and discuss
      how the features of the extracellular field affect these quantities. We show
      through simulations that endogenous fields, associated with hippocampal theta and
      sharp waves, can greatly affect spike timing. These findings imply that local
      electric fields, generated by the cooperative action of brain cells, can
      influence the timing of neural activity.

PMID- 20130200
TI  - Intracellular redox state alters NMDA receptor response during aging through
      Ca2+/calmodulin-dependent protein kinase II.
AB  - The contribution of the NMDA receptors (NMDARs) to synaptic plasticity declines
      during aging, and the decline is thought to contribute to memory deficits. Here,
      we demonstrate that an age-related shift in intracellular redox state contributes
      to the decline in NMDAR responses through Ca(2+)/calmodulin-dependent protein
      kinase II (CaMKII). The oxidizing agent xanthine/xanthine oxidase (X/XO)
      decreased the NMDAR-mediated synaptic responses at hippocampal CA3-CA1 synapses
      in slices from young (3-8 months) but not aged (20-25 months) rats. Conversely,
      the reducing agent dithiothreitol (DTT) selectively enhanced NMDAR response to a
      greater extent in aged hippocampal slices. The enhancement of NMDAR responses
      facilitated induction of long-term potentiation in aged but not young animals.
      The DTT-mediated growth in the NMDAR response was not observed for the AMPA
      receptor-mediated synaptic responses. A similar increase was observed by
      intracellular application of the membrane-impermeable reducing agent, L
      glutathione (L-GSH), through the intracellular recording pipette, indicating that
      the increased NMDAR response was dependent on intracellular redox state. DTT
      enhancement of the NMDAR response was dependent on CaMKII activity and was
      blocked by the CaMKII inhibitor--myristoylated autocamtide-2-related inhibitory
      peptide (myr-AIP)--but not by inhibition of the activity of protein phosphatases-
      PP1 and calcineurin (CaN/PP2B) or protein kinase C. CaMKII activity assays
      established that DTT increased CaMKII activity in CA1 cytosolic extracts in aged
      but not in young animals. These findings indicate a link between oxidation of
      CaMKII during aging, a decline in NMDAR responses, and altered synaptic
      plasticity.

PMID- 20130202
TI  - Selective electrical stimulation of the auditory nerve activates a pathway
      specialized for high temporal acuity.
AB  - Deaf people who use cochlear implants show surprisingly poor sensitivity to the
      temporal fine structure of sounds. One possible reason is that conventional
      cochlear implants cannot activate selectively the auditory-nerve fibers having
      low characteristic frequencies (CFs), which, in normal hearing, phase lock to
      stimulus fine structure. Recently, we tested in animals an alternative mode of
      auditory prosthesis using penetrating auditory-nerve electrodes that permit
      frequency-specific excitation in all frequency regions. We present here measures
      of temporal transmission through the auditory brainstem, from pulse trains
      presented with various auditory-nerve electrodes to phase-locked activity of
      neurons in the central nucleus of the inferior colliculus (ICC). On average,
      intraneural stimulation resulted in significant ICC phase locking at higher pulse
      rates (i.e., higher "limiting rates") than did cochlear-implant stimulation. That
      could be attributed, however, to the larger percentage of low-CF neurons
      activated selectively by intraneural stimulation. Most ICC neurons with limiting
      rates >500 pulses per second had CFs <1.5 kHz, whereas neurons with lower
      limiting rates tended to have higher CFs. High limiting rates also correlated
      strongly with short first-spike latencies. It follows that short latencies
      correlated significantly with low CFs, opposite to the correlation observed with
      acoustical stimulation. These electrical-stimulation results reveal a high
      temporal-acuity brainstem pathway characterized by low CFs, short latencies, and
      high-fidelity transmission of periodic stimulation. Frequency-specific
      stimulation of that pathway by intraneural stimulation might improve temporal
      acuity in human users of a future auditory prosthesis, which in turn might
      improve musical pitch perception and speech reception in noise.

PMID- 20130203
TI  - Vibrissa-based object localization in head-fixed mice.
AB  - Linking activity in specific cell types with perception, cognition, and action,
      requires quantitative behavioral experiments in genetic model systems such as the
      mouse. In head-fixed primates, the combination of precise stimulus control,
      monitoring of motor output, and physiological recordings over large numbers of
      trials are the foundation on which many conceptually rich and quantitative
      studies have been built. Choice-based, quantitative behavioral paradigms for head
      fixed mice have not been described previously. Here, we report a somatosensory
      absolute object localization task for head-fixed mice. Mice actively used their
      mystacial vibrissae (whiskers) to sense the location of a vertical pole presented
      to one side of the head and reported with licking whether the pole was in a
      target (go) or a distracter (no-go) location. Mice performed hundreds of trials
      with high performance (>90% correct) and localized to <0.95 mm (<6 degrees of
      azimuthal angle). Learning occurred over 1-2 weeks and was observed both within
      and across sessions. Mice could perform object localization with single whiskers.
      Silencing barrel cortex abolished performance to chance levels. We measured
      whisker movement and shape for thousands of trials. Mice moved their whiskers in
      a highly directed, asymmetric manner, focusing on the target location.
      Translation of the base of the whiskers along the face contributed substantially
      to whisker movements. Mice tended to maximize contact with the go (rewarded)
      stimulus while minimizing contact with the no-go stimulus. We conjecture that
      this may amplify differences in evoked neural activity between trial types.

PMID- 20130205
TI  - Evolutionary emergence of N-glycosylation as a variable promoter of HCN channel
      surface expression.
AB  - All four mammalian hyperpolarization-activated cyclic nucleotide-modulated (HCN)
      channel isoforms have been shown to undergo N-linked glycosylation in the brain.
      With the mouse HCN2 isoform as a prototype, HCN channels have further been
      suggested to require N-glycosylation for function, a provocative finding that
      would make them unique in the voltage-gated potassium channel superfamily. Here,
      we show that both the HCN1 and HCN2 isoforms are also predominantly N
      glycosylated in the embryonic heart, where they are found in significant amounts
      and where HCN-mediated currents are known to regulate beating frequency.
      Surprisingly, we find that N-glycosylation is not required for HCN2 function,
      although its cell surface expression is highly dependent on the presence of N
      glycans. Comparatively, disruption of N-glycosylation only modestly impacts cell
      surface expression of HCN1 and leaves permeation and gating functions almost
      unchanged. This difference between HCN1 and HCN2 is consistent with evolutionary
      trajectories that diverged in an isoform-specific manner after gene duplication
      from a common HCN ancestor that lacked N-glycosylation and was able to localize
      efficiently to the cell surface.

PMID- 20130204
TI  - Medial frontal cortex motivates but does not control movement initiation in the
      countermanding task.
AB  - Voluntary control of behavior implies the ability to select what action is
      performed. The supplementary motor area (SMA) and pre-SMA are widely considered
      to be of central importance for this ability because of their role in movement
      initiation and inhibition. To test this hypothesis, we recorded from neurons in
      SMA and pre-SMA of monkeys performing an arm countermanding task. Temporal
      analysis of neural activity and behavior in this task allowed us to test whether
      neural activity is sufficient to control movement initiation or inhibition.
      Surprisingly, 99% (242 of 243) of movement-related neurons in SMA and pre-SMA
      failed to exhibit time-locked activity changes predictive of movement initiation
      in this task. We also found a second group of neurons that was more active during
      successful response cancelation. Of these putative inhibitory cells, 18% (7 of
      40) responded early enough to be able to influence the cancelation of the
      movement. Thus, when tested with the countermanding task, the SMA/pre-SMA region
      may play a role in movement inhibition but does not appear to control movement
      initiation. However, the activity of 76% (202 of 267) of movement-related neurons
      was contingent on the expectation of reward and 42% of them reflected the amount
      of expected reward. These findings suggest that the movement-related activity in
      pre-SMA and SMA might represent the motivation for a specific action but does not
      determine whether or not that action is performed. This motivational signal in
      pre-SMA and SMA could provide an essential link between reward expectation and
      motor execution.

PMID- 20130206
TI  - Excitation-contraction coupling alterations in mdx and utrophin/dystrophin double
      knockout mice: a comparative study.
AB  - The double knockout mouse for utrophin and dystrophin (utr(-/-)/mdx) has been
      proposed to be a better model of Duchenne Muscular Dystrophy (DMD) than the mdx
      mouse because the former displays more similar muscle pathology to that of the
      DMD patients. In this paper the properties of action potentials (APs) and Ca(2+)
      transients elicited by single and repetitive stimulation were studied to
      understand the excitation-contraction (EC) coupling alterations observed in
      muscle fibers from mdx and utr(-/-)/mdx mice. Based on the comparison of the AP
      durations with those of fibers from wild-type (WT) mice, fibers from both mdx and
      utr(-/-)/mdx mice could be divided in two groups: fibers with WT-like APs (group
      1) and fibers with significantly longer APs (group 2). Although the proportion of
      fibers in group 2 was larger in utr(-/-)/mdx (36%) than in mdx mice (27%), the
      Ca(2+) release elicited by single stimulation was found to be similarly depressed
      (32-38%) in utr(-/-)/mdx and mdx fibers compared with WT counterparts regardless
      of the fiber's group. Stimulation at 100 Hz revealed that, with the exception of
      those from utr(-/-)/mdx mice, group 1 fibers were able to sustain Ca(2+) release
      for longer than group 2 fibers, which displayed an abrupt limitation even at the
      onset of the train. The differences in behavior between fibers in groups 1 and 2
      became almost unnoticeable at 50 Hz stimulation. In general, fibers from utr(-/
      )/mdx mice seem to display more persistent alterations in the EC coupling than
      those observed in the mdx model.

PMID- 20130207
TI  - Silencing of Mustn1 inhibits myogenic fusion and differentiation.
AB  - Mustn1 (Mustang, musculoskeletal temporally activated novel gene) was originally
      identified in fracture callus tissue, but its greatest expression is detected in
      skeletal muscle. Thus, we conducted experiments to investigate the expression and
      function of Mustn1 during myogenesis. Temporally, quantitative real-time PCR
      analysis of muscle samples from embryonic day 17 to 12 mo of age reveals that
      Mustn1 mRNA expression is greatest at 3 mo of age and beyond, consistent with the
      expression pattern of Myod. In situ hybridization shows abundant Mustn1
      expression in somites and developing skeletal muscles, while in adult muscle,
      Mustn1 is localized to some peripherally located nuclei. Using RNA interference
      (RNAi), we investigated the function of Mustn1 in C2C12 myoblasts. Though
      silencing Mustn1 mRNA had no effect on myoblast proliferation, it did
      significantly impair myoblast differentiation, preventing myofusion.
      Specifically, when placed in low-serum medium for up to 6 days, Mustn1-silenced
      myoblasts elongated poorly and were mononucleated. In contrast, control RNAi
      treated and parental myoblasts presented as large, multinucleated myotubes.
      Further supporting the morphological observations, immunocytochemistry of Mustn1
      silenced cells demonstrated significant reductions in myogenin (Myog) and myosin
      heavy chain (Myhc) expression at 4 and 6 days of differentiation as compared with
      control and parental cells. The decreases in Myog and Myhc protein expression in
      Mustn1-silenced cells were associated with robust ( approximately 3-fold or
      greater) decreases in the expression of Myod and desmin (Des), as well as the
      myofusion markers calpain 1 (Capn1), caveolin 3 (Cav3), and cadherin 15 (M
      cadherin; Cadh15). Overall, we demonstrate that Mustn1 is an essential regulator
      of myogenic differentiation and myofusion, and our findings implicate Myod and
      Myog as its downstream targets.

PMID- 20130208
TI  - Functional ion channels in mouse cardiac c-kit(+) cells.
AB  - Cardiac c-kit(+) cells are generally believed to be the major population of
      stem/progenitor cells in the heart and can be used as a cell source for
      cardiomyoplasty; however, the cellular electrophysiological properties are not
      understood in this type of cells. The present study was designed to investigate
      functional ion channels in undifferentiated mouse cardiac c-kit(+) cells using
      approaches of whole cell patch voltage clamp, RT-PCR, and cell proliferation
      assay. It was found that three types of ionic currents were present in mouse
      cardiac c-kit(+) cells, including a delayed rectifier K(+) current (IK(DR))
      inhibited by 4-aminopyridine (4-AP), an inward rectifier K(+) current (I(Kir))
      decreased by Ba(2+), and a volume-sensitive chloride current (I(Cl.vol))
      inhibited by 5-nitro-1-(3-phenylpropylamino) benzoic acid (NPPB). RT-PCR revealed
      that the corresponding ion channel genes, Kv1.1, Kv1.2, and Kv1.6 (for IK(DR)),
      Kir.1.1, Kir2.1, and Kir2.2 (likely responsible for I(Kir)), and Clcn3 (for
      I(Cl.vol)), were significant in mouse cardiac c-kit(+) cells. The inhibition of
      I(Cl.vol) with NPPB and niflumic acid, but not IK(DR) with 4-AP and
      tetraethylammonium, reduced cell proliferation and accumulated the cell
      progression at G(0)/G(1) phase in mouse cardiac c-kit(+) cells. Our results
      demonstrate that three types of functional ion channel currents (i.e., IK(DR),
      I(Kir), and I(Cl.vol)) are present in mouse cardiac c-kit(+) cells, and I(Cl.vol)
      participates in regulating cell proliferation.

PMID- 20130209
TI  - The Feynman trajectories: determining the path of a protein using fixed-endpoint
      assays.
AB  - Richard Feynman postulated in 1948 that the path of an electron can be best
      described by the sum or functional integral of all possible trajectories rather
      than by the notion of a single, unique trajectory. As a consequence, the position
      of an electron does not harbor any information about the paths that contributed
      to this position. This observation constitutes a classical endpoint observation.
      The endpoint assay is the desired type of experiment for high-throughput
      screening applications, mainly because of limitations in data acquisition and
      handling. Quite contrary to electrons, it is possible to extract information
      about the path of a protein using endpoint assays, and these types of
      applications are reviewed in this article.

PMID- 20130210
TI  - A physiological function of inflammation-associated SerpinB2 is regulation of
      adaptive immunity.
AB  - SerpinB2 (plasminogen activator inhibitor-2) is widely described as an inhibitor
      of urokinase plasminogen activator; however, SerpinB2(-/-) mice show no
      detectable increase in urokinase plasminogen activator activity. In this study,
      we describe an unexpected immune phenotype in SerpinB2(-/-) mice. After
      immunization with OVA in CFA, SerpinB2(-/-) mice made approximately 6-fold more
      IgG2c and generated approximately 2.5-fold more OVA-specific IFN-gamma-secreting
      T cells than SerpinB2(+/+) littermate controls. In SerpinB2(+/+) mice, high
      inducible SerpinB2 expression was seen at the injection site and in macrophages
      low levels in draining lymph nodes and conventional dendritic cells, and no
      expression was seen in plasmacytoid dendritic, B, T, or NK cells. SerpinB2(-/-)
      macrophages promoted greater IFN-gamma secretion from wild-type T cells in vivo
      and in vitro and, when stimulated with anti-CD40/IFN-gamma or cultured with wild
      type T cells in vitro, secreted more Th1-promoting cytokines than macrophages
      from littermate controls. Draining lymph node SerpinB2(-/-) myeloid APCs
      similarly secreted more Th1-promoting cytokines when cocultured with wild-type T
      cells. Regulation of Th1 responses thus appears to be a physiological function of
      inflammation-associated SerpinB2; an observation that may shed light on human
      inflammatory diseases like pre-eclampsia, lupus, asthma, scleroderma, and
      periodontitis, which are associated with SerpinB2 polymorphisms or dysregulated
      SerpinB2 expression.

PMID- 20130211
TI  - C-type lectin SIGN-R1 has a role in experimental colitis and responsiveness to
      lipopolysaccharide.
AB  - Pathogen recognition receptors (PRRs) function to maintain the balance between
      controlled responses to pathogens and uncontrolled innate immune activation
      leading to inflammation. In the context of commensal bacteria and the etiology of
      inflammatory bowel disease, although a role for the TLRs is known, there is a
      less defined function for C-type lectin receptors (CLRs). We demonstrate that
      mice deficient ((-/-)) in the CLR specific intracellular adhesion molecule-3
      grabbing nonintegrin homolog-related 1 (SIGN-R1) (CD209b) have reduced
      susceptibility to experimental colitis, with a reduction in the disease severity,
      colon damage, and levels of the proinflammatory cytokines IL-1beta, TNF-alpha,
      and IL-6. To determine whether SIGN-R1(-/-) mice had a systemic defect in innate
      activation, we examined the responsiveness of macrophages from SIGN-R1(-/-) mice
      to TLR ligands. SIGN-R1(-/-) peritoneal macrophages, but not bone marrow-derived
      macrophages, have a specific defect in IL-1beta and IL-18 production, but not
      other cytokines, in response to the TLR4 ligand LPS. In vivo SIGN-R1(-/-) mice
      had significantly reduced susceptibility to LPS-induced shock. To address the
      synergistic relationship between SIGN-R1 and TLR4 in the context of experimental
      colitis, SIGN-R1/TLR4(-/-) mice were generated. SIGN-R1/TLR4(-/-) mice displayed
      reduced susceptibility to experimental colitis relative to severity of disease
      observed in wild-type or TLR4(-/-) mice. The in vivo use of a blocking mAb
      confirmed a functional role for SIGN-R1 in LPS-induced shock and experimental
      colitis. These data indicate a role for SIGN-R1 in the regulation of inflammation
      in a model of experimental colitis and illustrate that SIGN-R1 is a critical
      innate factor in response to LPS.

PMID- 20130212
TI  - Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell
      adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression.
AB  - Cell-cell adhesion mediated by ICAM-1 and VCAM-1 is critical for T cell
      activation and leukocyte recruitment to the inflammation site and, therefore,
      plays an important role in evoking effective immune responses. However, we found
      that ICAM-1 and VCAM-1 were critical for mesenchymal stem cell (MSC)-mediated
      immunosuppression. When MSCs were cocultured with T cells in the presence of T
      cell Ag receptor activation, they significantly upregulated the adhesive
      capability of T cells due to the increased expression of ICAM-1 and VCAM-1. By
      comparing the immunosuppressive effect of MSCs toward various subtypes of T cells
      and the expression of these adhesion molecules, we found that the greater
      expression of ICAM-1 and VCAM-1 by MSCs, the greater the immunosuppressive
      capacity that they exhibited. Furthermore, ICAM-1 and VCAM-1 were found to be
      inducible by the concomitant presence of IFN-gamma and inflammatory cytokines
      (TNF-alpha or IL-1). Finally, MSC-mediated immunosuppression was significantly
      reversed in vitro and in vivo when the adhesion molecules were genetically
      deleted or functionally blocked, which corroborated the importance of cell-cell
      contact in immunosuppression by MSCs. Taken together, these findings reveal a
      novel function of adhesion molecules in immunoregulation by MSCs and provide new
      insights for the clinical studies of antiadhesion therapies in various immune
      disorders.

PMID- 20130213
TI  - MicroRNA regulation of IFN-beta protein expression: rapid and sensitive
      modulation of the innate immune response.
AB  - IFN-beta production is an inaugural event in the innate immune response to viral
      infections, with relatively small fold changes in IFN-beta expression resulting
      in the activation of important antiviral signaling cascades. In our rapid
      SIV/macaque model of HIV encephalitis, the virus enters the CNS within 4 d of
      infection, accompanied by a marked IFN-beta response that wanes as SIV
      replication is controlled. The centrality of IFN-beta to the innate antiviral
      response in the CNS combines with the potential inflammatory damage associated
      with long-term activation of this pathway to suggest that IFN-beta may be subject
      to regulatory fine-tuning in addition to well-established transcriptional and
      message stability mechanisms of regulation. In this paper, we present for the
      first time evidence that microRNAs (miRNAs), including miR-26a, -34a, -145, and
      let-7b, may directly regulate IFN-beta in human and macaque cells. In primary
      primate macrophages, the main cell type implicated in HIV and SIV infection in
      the CNS, specific miRNAs reduce, whereas miRNA inhibitors enhance, IFN-beta
      protein production. The potential biologic significance of this regulation is
      supported by evidence of an apparent negative feedback loop, with increased
      expression of three IFN-beta-regulating miRNAs by primate macrophages exposed to
      recombinant IFN-beta or stimulated to produce IFN-beta. Thus, miRNAs may
      contribute significantly to the regulation of IFN-beta in innate immune
      responses.

PMID- 20130214
TI  - Distinct phenotype and function of NK cells in the pancreas of nonobese diabetic
      mice.
AB  - Little is known about target organ-infiltrating NK cells in type 1 diabetes and
      other autoimmune diseases. In this study, we identified NK cells with a unique
      phenotype in the pancreas of NOD mice. Pancreatic NK cells, localized to the
      endocrine and exocrine parts, were present before T cells during disease
      development and did not require T cells for their infiltration. Furthermore, NK
      cells, or NK cell precursors, from the spleen could traffic to the pancreas,
      where they displayed the pancreatic phenotype. Pancreatic NK cells from other
      mouse strains shared phenotypic characteristics with pancreatic NK cells from NOD
      mice, but displayed less surface killer cell lectin-like receptor G1, a marker
      for mature NK cells that have undergone proliferation, and also did not
      proliferate to the same extent. A subset of NOD mouse pancreatic NK cells
      produced IFN-gamma spontaneously, suggesting ongoing effector responses. However,
      most NOD mouse pancreatic NK cells were hyporesponsive compared with spleen NK
      cells, as reflected by diminished cytokine secretion and a lower capacity to
      degranulate. Interestingly, such hyporesponsiveness was not seen in pancreatic NK
      cells from the nonautoimmune strain C57BL/6, suggesting that this feature is not
      a general property of pancreatic NK cells. Based on our data, we propose that NK
      cells are sentinel cells in a normal pancreas. We further speculate that during
      inflammation, pancreatic NK cells initially mediate proinflammatory effector
      functions, potentially contributing to organ-specific autoimmunity, but later
      become hyporesponsive because of exhaustion or regulation.

PMID- 20130215
TI  - The role of the LAT-PLC-gamma1 interaction in T regulatory cell function.
AB  - The interaction between the linker for activation of T cells (LAT) with PLC
      gamma1 is important for TCR-mediated Ca(2+) signaling and MAPK activation. Knock
      in mice harboring a mutation at the PLC-gamma1 binding site (Y136) of LAT develop
      a severe lymphoproliferative syndrome. These mice have defective thymic
      development and selection and lack natural regulatory T cells, implicating a
      breakdown of both central and peripheral tolerance. To bypass this developmental
      defect, we developed a conditional knock-in line in which only LATY136F is
      expressed in mature T cells after deletion of the wild type LAT allele. Analysis
      of LATY136F T cells indicated that the interaction between LAT and PLC-gamma1
      plays an important role in TCR-mediated signaling, proliferation, and IL-2
      production. Furthermore, the deletion of LAT induced development of the
      lymphoproliferative syndrome in these mice. Although Foxp3(+) natural Treg cells
      were present in these mice after deletion, they were unable to suppress the
      proliferation of conventional T cells. Our data indicate that the binding of LAT
      to PLC-gamma1 is essential for the suppressive function of CD4(+)CD25(+)
      regulatory T cells.

PMID- 20130216
TI  - Cutting edge: bacterial infection induces hematopoietic stem and progenitor cell
      expansion in the absence of TLR signaling.
AB  - Bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) can be activated
      by type I IFNs, TLR agonists, viruses, and bacteria to increase hematopoiesis. In
      this study, we report that endotoxin treatment in vivo induces TLR4, MyD88, and
      Toll/IL-1 resistance domain-containing adaptor-inducing IFN-beta (TRIF)-dependent
      expansion of BM HSPCs. Bacterial infection by Staphylococcus aureus or cecal
      ligation and puncture also induces HSPC expansion, but MyD88, TRIF, type I IFN,
      cytokine, PG, or oxidative stress pathways are not required for their expansion.
      S. aureus-induced HSPC expansion in MyD88(-/-)TRIF(-/-) mice is also normal, but
      is associated with BM remodeling as granulocyte stores are released peripherally.
      Importantly, reduction in BM cellularity alone can reproduce HSPC expansion.
      These data show in vivo HSPC responses to bacterial infection are complex and not
      absolutely dependent upon key inflammatory signaling pathways.

PMID- 20130217
TI  - The single IgG IL-1-related receptor controls TLR responses in differentiated
      human intestinal epithelial cells.
AB  - Intestinal epithelial cells (IECs) are constantly exposed to enteric microbes.
      Although IECs express TLRs that recognize bacterial products, the activation of
      these TLRs is strictly controlled through poorly understood mechanisms, producing
      a state of hyporesponsiveness and preventing unwanted inflammation. The single
      IgG IL-1-related receptor (Sigirr) is a negative regulator of TLRs that is
      expressed by IECs and was recently shown to inhibit experimental colitis.
      However, the importance of Sigirr in IEC hyporesponsiveness and its distribution
      within the human colon is unknown. In this study, we investigated the role of
      Sigirr in regulating epithelial-specific TLR responses and characterized its
      expression in colonic biopsy specimens. Transformed and nontransformed human IECs
      were cultured as monolayers. Transient gene silencing and stable overexpression
      of Sigirr was performed to assess innate IEC responses. Sigirr expression in
      human colonic biopsy specimens was examined by immunohistochemistry. Bacterial
      infection of IECs and exposure to flagellin transiently decreased Sigirr protein
      expression, concurrent with secretion of the neutrophil chemokine IL-8. Sigirr
      gene silencing augmented chemokine responses to bacterial flagellin, Pam3Cys, and
      the cytokine IL-1beta. Conversely, stable overexpression of Sigirr diminished NF
      kappaB-mediated IL-8 responses to TLR ligands. We also found that Sigirr
      expression increased as IECs differentiated in culture. This observation was
      confirmed in biopsy sections, in which Sigirr expression within colonic crypts
      was prominent in IECs at the apex and diminished at the base. Our findings show
      that Sigirr broadly regulates innate responses in differentiated human IECs;
      therefore, it may modulate epithelial involvement in infectious and inflammatory
      bowel diseases.

PMID- 20130218
TI  - Importance of cytokines in murine allergic airway disease and human asthma.
AB  - Asthma is a common, disabling inflammatory respiratory disease that has increased
      in frequency and severity in developed nations. We review studies of murine
      allergic airway disease (MAAD) and human asthma that evaluate the importance of
      Th2 cytokines, Th2 response-promoting cytokines, IL-17, and proinflammatory and
      anti-inflammatory cytokines in MAAD and human asthma. We discuss murine studies
      that directly stimulate airways with specific cytokines or delete, inactivate,
      neutralize, or block specific cytokines or their receptors, as well as
      controversial issues including the roles of IL-5, IL-17, and IL-13Ralpha2 in MAAD
      and IL-4Ralpha expression by specific cell types. Studies of human asthmatic
      cytokine gene and protein expression, linkage of cytokine polymorphisms to
      asthma, cytokine responses to allergen stimulation, and clinical responses to
      cytokine antagonists are discussed as well. Results of these analyses establish
      the importance of specific cytokines in MAAD and human asthma and have
      therapeutic implications.

PMID- 20130219
TI  - Inflammatory mechanisms in ischemic stroke: role of inflammatory cells.
AB  - Inflammation plays an important role in the pathogenesis of ischemic stroke and
      other forms of ischemic brain injury. Experimentally and clinically, the brain
      responds to ischemic injury with an acute and prolonged inflammatory process,
      characterized by rapid activation of resident cells (mainly microglia),
      production of proinflammatory mediators, and infiltration of various types of
      inflammatory cells (including neutrophils, different subtypes of T cells,
      monocyte/macrophages, and other cells) into the ischemic brain tissue. These
      cellular events collaboratively contribute to ischemic brain injury. Despite
      intense investigation, there are still numerous controversies concerning the time
      course of the recruitment of inflammatory cells in the brain and their pathogenic
      roles in ischemic brain injury. In this review, we provide an overview of the
      time-dependent recruitment of different inflammatory cells following focal
      cerebral I/R. We discuss how these cells contribute to ischemic brain injury and
      highlight certain recent findings and currently unanswered questions about
      inflammatory cells in the pathophysiology of ischemic stroke.

PMID- 20130220
TI  - Potent intestinal Th17 priming through peripheral lipopolysaccharide-based
      immunization.
AB  - Lipopolysaccharide (LPS) is a potent natural adjuvant, commonly used to amplify
      Th1 responses. Here, we report that systemic immunization using LPS generates
      large numbers of specific Th17 cells in murine small intestinal lamina propria.
      The priming of these Th17 cells required IL-23p19 production by bone marrow
      derived cells. In contrast, IL-23 had no impact on Th1 differentiation or overall
      numbers of Ag-specific regulatory T cells. Experiments using T-cell adoptive
      transfers revealed a previously unappreciated mechanism for how Th17 responses
      are amplified in vivo: stimulation through LPS expanded precommitted Th17 cells
      rather than causing Th17 differentiation. Second, LPS drove Th17 cell expansion
      independently of IL-23, demonstrating that this cytokine is not necessary for
      expansion and possibly functions at an earlier stage in Th17 priming. Our data
      provide an impetus for using LPS-based peripheral vaccination to augment specific
      T-cell-mediated immunity in the gut mucosa.

PMID- 20130221
TI  - HIV DNA in circulating monocytes as a mechanism to dementia and other HIV
      complications.
AB  - It is broadly accepted that HIV DNA in lymphoid and myeloid cells persists
      despite combination antiretroviral therapy. Recognized as the Achilles heel to
      HIV eradication, the role of these peripheral reservoirs in HIV morbidity is less
      well developed. The burden of HIV DNA in peripheral mononuclear cells is linked
      to HIV disease outcomes such as time to AIDS diagnosis, survival, and CD4 T
      lymphocyte counts. Monocytes are a minor HIV DNA reservoir, and the burden of HIV
      DNA in these cells appears to be linked to dementia, suggesting that residual
      infection in this subset is linked to tissue-related HIV complications. Since
      monocytes are likely involved in trafficking virus to the brain, there is a
      strong mechanistic link underlying this discovery. Herein, we summarize our
      current understanding of monocyte HIV DNA and central nervous system dysfunction
      in humans. We present a model to understand these relationships and suggest
      possible treatment approaches to be tested.

PMID- 20130222
TI  - Comparative analysis of nitrite uptake and hemoglobin-nitrite reactions in
      erythrocytes: sorting out uptake mechanisms and oxygenation dependencies.
AB  - Nitrite uptake into red blood cells (RBCs) precedes its intracellular reactions
      with hemoglobin (Hb) that forms nitric oxide (NO) during hypoxia. We investigated
      the uptake of nitrite and its reactions with Hb at different oxygen saturations
      (So(2)), using RBCs with (carp and rabbit) and without (hagfish and lamprey)
      anion exchanger-1 (AE1) in the membrane, with the aim to unravel the mechanisms
      and oxygenation dependencies of nitrite transport. Added nitrite rapidly diffused
      into the RBCs until equilibrium. The distribution ratio of nitrite across the
      membrane agreed with that expected from HNO(2) diffusion and AE1-mediated
      facilitated NO(2)(-) diffusion. Participation of HNO(2) diffusion was emphasized
      by rapid transmembrane nitrite equilibration also in the natural AE1 knockouts.
      Following the equilibration, nitrite was consumed by reacting with Hb, which
      created a continued inward diffusion controlled by intracellular reaction rates.
      Changes in nitrite uptake with So(2), pH, or species were accordingly explained
      by corresponding changes in reaction rates. In carp, nitrite uptake rates
      increased linearly with decreasing So(2) over the entire So(2) range. In rabbit,
      nitrite uptake rates were highest at intermediate So(2), producing a bell-shaped
      relationship with So(2). Nitrite consumption increased approximately 10-fold with
      a 1 unit decrease in pH, as expected from the involvement of protons in the
      reactions with Hb. The reaction of nitrite with deoxyhemoglobin was favored over
      that with oxyhemoglobin at intermediate So(2). We propose a model for RBC nitrite
      uptake that involves both HNO(2) diffusion and AE1-mediated transport and that
      explains both the present and previous (sometimes puzzling) results.

PMID- 20130223
TI  - Serotonin neurons of the caudal raphe nuclei contribute to sympathetic recovery
      following hypotensive hemorrhage.
AB  - Serotonin is thought to contribute to the syncopal-like response that develops
      during severe blood loss by inhibiting presympathetic neurons of the
      rostroventrolateral medulla (RVLM). Here, we tested whether serotonin cells
      activated during hypotensive hemorrhage, i.e., express the protein product of the
      immediate early gene c-Fos, are critical for the normal sympathetic response to
      blood loss in unanesthetized rats. Serotonin-immunoreactive cells of the raphe
      obscurus and raphe magnus, parapyramidal cells of the B3 region, subependymal
      cells of the ventral parapyramidal region, and cells of the ventrolateral
      periaqueductal gray region were activated by hypotensive hemorrhage, but not by
      hypotension alone. In contrast to findings in anesthetized animals, lesion of
      hindbrain serotonergic cells sufficient to produce >80% loss of serotonin nerve
      terminal immunoreactivity in the RVLM accelerated the sympatholytic response to
      blood loss, attenuated recovery of sympathetic activity after termination of
      hemorrhage, and exaggerated metabolic acidosis. Hindbrain serotonin lesion also
      attenuated ventilatory and sympathetic responses to stimulation of central
      chemoreceptors but increased spontaneous arterial baroreflex sensitivity and
      decreased blood pressure variability. A more global neurotoxic lesion that also
      eliminated tryptophan hydroxylase-immunoreactive cells of the ventrolateral
      periaqueductal gray region had no further effect on the sympatholytic response to
      blood loss. Together, the data indicate that serotonin cells of the caudal
      hindbrain contribute to compensatory responses following blood loss that help
      maintain oxygenation of peripheral tissue in the unanesthetized rat. This effect
      may be related to facilitation of chemoreflex responses to acidosis.

PMID- 20130224
TI  - The O2 cost of the tension-time integral in isolated single myocytes during
      fatigue.
AB  - One proposed explanation for the Vo(2) slow component is that lower-threshold
      motor units may fatigue and develop little or no tension but continue to use
      O(2), thereby resulting in a dissociation of cellular respiration from force
      generation. The present study used intact isolated single myocytes with differing
      fatigue resistance profiles to investigate the relationship between fatigue,
      tension development, and aerobic metabolism. Single Xenopus skeletal muscle
      myofibers were allocated to a fast-fatiguing (FF) or a slow-fatiguing (SF) group,
      based on the contraction frequency required to elicit a fall in tension to 60% of
      peak. Phosphorescence quenching of a porphyrin compound was used to determine
      Delta intracellular Po(2) (Pi(O(2)); a proxy for Vo(2)), and developed isometric
      tension was monitored to allow calculation of the time-integrated tension (TxT).
      Although peak DeltaPi(O(2)) was not different between groups (P = 0.36), peak
      tension was lower (P < 0.05) in SF vs. FF (1.97 +/- 0. 17 V vs. 2. 73 +/- 0.30 V,
      respectively) and time to 60% of peak tension was significantly longer in SF vs.
      FF (242 +/- 10 s vs. 203 +/- 10 s, respectively). Before fatigue, both
      DeltaPi(O(2)) and TxT rose proportionally with contraction frequency in SF and
      FF, resulting in DeltaPi(O(2))/TxT being identical between groups. At fatigue,
      TxT fell dramatically in both groups, but DeltaPi(O(2)) decreased proportionately
      only in the FF group, resulting in an increase in DeltaPi(O(2))/TxT in the SF
      group relative to the prefatigue condition. These data show that more fatigue
      resistant fibers maintain aerobic metabolism as they fatigue, resulting in an
      increased O(2) cost of contractions that could contribute to the Vo(2) slow
      component seen in whole body exercise.

PMID- 20130225
TI  - Roles of CYP2C29 and RXR gamma in vascular EET synthesis of female mice.
AB  - We aimed to identify which cytochrome P-450 (CYP) family/subfamily, as well as
      related transcription factor(s), is responsible for the estrogen-dependent
      synthesis of epoxyeicosatrienoic acids (EETs) to initiate shear stress-induced
      vasodilation. Microarray analysis indicated a significant upregulation of CYP2C29
      and retinoid X receptor gamma (RXRgamma) in isolated mesenteric
      arteries/arterioles of female endothelial nitric oxide synthase-knockout mice, a
      result that was validated by real-time RT-PCR. The cannulated vessels were then
      perfused with 2 and 10 dyn/cm(2) shear stress, followed by collection of the
      perfusate to determine EET concentrations and isoforms. Shear stress dose
      dependently stimulated the release of EETs into the perfusate, associated with an
      EET-mediated vasodilation, in which predominantly 14,15-EET and 11,12-EET
      contributed to the responses ( approximately 87.4% of total EETs). Transfection
      of vessels with CYP2C29 siRNA eliminated the release of EETs into the perfusate,
      which was evidenced by an abolished vasodilation, and confirmed by RT-PCR and
      Western blot analyses. Knockdown of RXRgamma in these vessels significantly
      inhibited the production of EETs, parallel to a reduced vasodilation. RXRgamma
      siRNA not only silenced the vascular RXRgamma expression, but synchronously
      downregulated CYP2C29 expression, leading to a reduced EET synthesis. In
      conclusion, our data provide the first evidence for a specific signaling cascade,
      by which estrogen potentially activates the CYP2C29 gene in the absence of nitric
      oxide, to synthesize EETs in response to shear stress, via an RXRgamma-related
      regulatory mechanism.

PMID- 20130226
TI  - HCO (3)(-) secretion and CaCO3 precipitation play major roles in intestinal water
      absorption in marine teleost fish in vivo.
AB  - The intestine of marine teleosts must effectively absorb fluid from ingested
      seawater to avoid dehydration. This fluid transport has been almost exclusively
      characterized as driven by NaCl absorption. However, an additional feature of the
      osmoregulatory role of the intestine is substantial net HCO(3)(-) secretion. This
      is suggested to drive additional fluid absorption directly (via Cl(-)/HCO(3)(-)
      exchange) and indirectly by precipitating ingested Ca(2+) as CaCO(3), thus
      creating the osmotic gradient for additional fluid absorption. The present study
      tested this hypothesis by perfusing the intestine of the European flounder in
      vivo with varying [Ca(2+)]: 10 (control), 40, and 90 mM. Fractional fluid
      absorption increased from 47% (control) to 73% (90 mM Ca(2+)), where almost all
      secreted HCO(3)(-) was excreted as CaCO(3). This additional fluid absorption
      could not be explained by NaCl cotransport. Instead, a significant positive
      relationship between Na(+)-independent fluid absorption and total HCO(3)(-)
      secretion was consistent with the predicted roles for anion exchange and CaCO(3)
      precipitation. Further analysis suggested that Na(+)-independent fluid absorption
      could be accounted for by net Cl(-) and H(+) absorption (from Cl(-)/HCO(3)(-)
      exchange and CO(2) hydration, respectively). There was no evidence to suggest
      that CaCO(3) alone was responsible for driving fluid absorption. However, by
      preventing the accumulation of luminal Ca(2+) it played a vital role by
      dynamically maintaining a favorable osmotic gradient all along the intestine,
      which permits substantially higher rates of solute-linked fluid absorption. To
      overcome the resulting hyperosmotic and highly acidic absorbate, it is proposed
      that plasma HCO(3)(-) buffers the absorbed H(+) (from HCO(3)(-) production), and
      consequently reduces the osmolarity of the absorbed fluid entering the body.

PMID- 20130227
TI  - Ca2+-driven intestinal HCO(3)(-) secretion and CaCO3 precipitation in the
      European flounder in vivo: influences on acid-base regulation and blood gas
      transport.
AB  - Marine teleost fish continuously ingest seawater to prevent dehydration and their
      intestines absorb fluid by mechanisms linked to three separate driving forces: 1)
      cotransport of NaCl from the gut fluid; 2) bicarbonate (HCO(3)(-)) secretion and
      Cl(-) absorption via Cl(-)/HCO(3)(-) exchange fueled by metabolic CO(2); and 3)
      alkaline precipitation of Ca(2+) as insoluble CaCO(3), which aids H(2)O
      absorption). The latter two processes involve high rates of epithelial HCO(3)(-)
      secretion stimulated by intestinal Ca(2+) and can drive a major portion of water
      absorption. At higher salinities and ambient Ca(2+) concentrations the
      osmoregulatory role of intestinal HCO(3)(-) secretion is amplified, but this has
      repercussions for other physiological processes, in particular, respiratory gas
      transport (as it is fueled by metabolic CO(2)) and acid-base regulation (as
      intestinal cells must export H(+) into the blood to balance apical HCO(3)(-)
      secretion). The flounder intestine was perfused in vivo with salines containing
      10, 40, or 90 mM Ca(2+). Increasing the luminal Ca(2+) concentration caused a
      large elevation in intestinal HCO(3)(-) production and excretion. Additionally,
      blood pH decreased (-0.13 pH units) and plasma partial pressure of CO(2) (Pco(2))
      levels were elevated (+1.16 mmHg) at the highest Ca perfusate level after 3 days
      of perfusion. Increasing the perfusate [Ca(2+)] also produced proportional
      increases in net acid excretion via the gills. When the net intestinal flux of
      all ions across the intestine was calculated, there was a greater absorption of
      anions than cations. This missing cation flux was assumed to be protons, which
      vary with an almost 1:1 relationship with net acid excretion via the gill. This
      study illustrates the intimate link between intestinal HCO(3)(-) production and
      osmoregulation with acid-base balance and respiratory gas exchange and the
      specific controlling role of ingested Ca(2+) independent of any other ion or
      overall osmolality in marine teleost fish.

PMID- 20130228
TI  - Cardiac response to startle stimuli in larval zebrafish: sympathetic and
      parasympathetic components.
AB  - Central regulation of cardiac output via the sympathetic and parasympathetic
      branches of the autonomic nervous system allows the organism to respond to
      environmental changes. Sudden onset stimuli, startle stimuli, are useful probes
      to study central regulatory responses to the environment. In mammals, startle
      stimuli induce a transient bradycardia that habituates with repeated stimulation.
      Repeated presentation of the stimulus results in tachycardia. In this study, we
      investigate the behavioral regulation of heart rate in response to sudden stimuli
      in the zebrafish. Larval zebrafish show a stereotyped heart rate response to mild
      electrical shock. Naive fish show a significant increase in interbeat interval
      that resolves in the 2 s following stimulation. This transient bradycardia
      decreases on repeated exposure to the stimulus. Following repeated stimulation,
      the fish become tachycardic within 1 min of stimulation. Both the transient
      bradycardia and following tachycardia responses are blocked with administration
      of the ganglionic blocker hexamethonium, demonstrating that these responses are
      mediated centrally. The transient bradycardia is blocked by the muscarinic
      antagonist atropine, suggesting that this response is mediated by the
      parasympathetic system, while the following tachycardia is specifically blocked
      by the beta-adrenergic antagonist propranolol, suggesting that this response is
      mediated by the sympathetic nervous system. Together, these results demonstrate
      that at the larval stage, zebrafish actively regulate cardiac output to changes
      in their environment using both the parasympathetic and sympathetic branches of
      the autonomic nervous system, a behavioral response that is markedly similar to
      that observed in mammals to similar sudden onset stimuli.

PMID- 20130229
TI  - Does immigration to Canada prevent stroke, eh?

PMID- 20130230
TI  - Risk of premature stroke in recent immigrants (PRESARIO): population-based
      matched cohort study.
AB  - BACKGROUND: New immigrants to North America, most of whom are under age 50 years,
      exhibit fewer risk factors for cardiovascular disease than their native-born
      counterparts, yet the stress of resettlement may conceivably place them at higher
      risk of stroke. We determined the risk of acute stroke associated with recency of
      immigration. METHODS: We completed a population-based matched cohort study in
      Ontario, the largest province in Canada, from April 1, 1995, to March 31, 2007.
      Overall, 965,829 new immigrants were matched to 3,272,393 long-term residents by
      year of birth, sex, and location. New immigrants were identified as new
      recipients of universally available public health insurance, and long-term
      residents were those insured for 5 years or longer. RESULTS: The mean age of the
      participants at study entry was about 34 years and the total number of observed
      strokes was 6,216 after a median duration of follow-up of about 6 years. The
      incidence rate of acute stroke was 1.69 per 10,000 person-years among new
      immigrants and 2.56 per 10,000 person-years among long-term residents (crude
      hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.62-0.71). After adjusting
      for age, income quintile, urban vs rural residence, history of hypertension,
      diabetes mellitus and smoking, and number of health insurance claims, the HR for
      stroke was 0.69 (95% CI 0.64-0.74). Similar risk estimates were seen for both
      ischemic and hemorrhagic stroke subtypes. CONCLUSION: New immigrants appear to be
      at lower risk of premature acute stroke than long-term residents. This finding
      does not appear to be explained by the availability of health care services or
      income level.

PMID- 20130231
TI  - IFN-gamma is a master regulator of endotoxin shock syndrome in mice primed with
      heat-killed Propionibacterium acnes.
AB  - Hyper-coagulation, hypothermia, systemic inflammatory responses and shock are
      major clinical manifestations of endotoxin shock syndrome in human. As previously
      reported, mice primed with heat-killed Propionibacterium acnes are highly
      susceptible to the action of LPS to induce tumour necrosis factor (TNF)-alpha and
      to that of TNF-alpha to trigger lethal shock. Here we investigated the mechanisms
      underlying the P. acnes-induced sensitization to LPS and TNF-alpha and the
      development of individual symptoms after subsequent challenge with LPS or TNF
      alpha. Propionibacterium acnes-primed wild-type (WT) mice, but not naive mice,
      exhibited hyper-coagulation with elevated levels of thrombin-antithrombin
      complexes and anti-fibrinolytic plasminogen activator inhibitor 1 in their
      plasma, hypothermia, systemic inflammatory responses and high mortality rate
      after LPS or TNF-alpha challenge. Propionibacterium acnes treatment reportedly
      induces both T(h)1 and T(h)17 cell development. Propionibacterium acnes-primed
      Il12p40(-/-) and Ifngamma(-/-) mice, while not Il17A(-/-) mice, evaded all these
      symptoms/signs upon LPS or TNF-alpha challenge, indicating essential requirement
      of IL-12-IFN-gamma axis for the sensitization to LPS and TNF-alpha. Furthermore,
      IFN-gamma blockade just before LPS challenge could prevent P. acnes-primed WT
      mice from endotoxin shock syndrome. These results demonstrated requirement of IFN
      gamma to the development of endotoxin shock and suggested it as a potent
      therapeutic target for the treatment of septic shock.

PMID- 20130232
TI  - Genetic association of the CCR5 region with lipid levels in at-risk
      cardiovascular patients.
AB  - BACKGROUND: There is mounting evidence to suggest that chemokine receptor 5
      (CCR5) plays an important role in the development and progression of
      atherosclerosis. A naturally occurring variant of the CCR5 gene CCR532, exists at
      allele frequencies of typically 10% in European populations and results in a
      nonfunctional CCR5 receptor. METHODS AND RESULTS: The CCR5Delta32 deletion and 26
      other variants within the chemokine receptor 2-CCR5-chemokine receptor-like
      protein 2 (CCRL2) gene cluster spanning 59 kilobases of chromosome 3 were
      genotyped in 5748 subjects from the Treating to New Targets atorvastatin trial to
      determine whether genetic associations could be identified with circulating lipid
      values and cardiovascular disease. Our results demonstrate an association between
      the CCR5Delta32 deletion and increased plasma high-density lipoprotein
      cholesterol and decreased plasma triglycerides, both of which are beneficial from
      a cardiovascular perspective. Three single-nucleotide polymorphisms (rs1154428,
      rs6808835, and rs6791599) in CCRL2 in linkage disequilibrium (r(2)> or =0.65)
      with CCR5Delta32 and located up to 45 kilobases distal to it were associated with
      high-density lipoprotein cholesterol. The high-density lipoprotein cholesterol
      and triglycerides findings were replicated in an additional set of >6000
      individuals from the Incremental Decrease in Endpoints through Aggressive Lipid
      Lowering atorvastatin trial. CONCLUSIONS: Our study provides evidence that a
      locus within the region of the genome encompassing the CCR5-CCRL2 region is
      associated with lipid levels and suggests that chemokine activity influences
      lipid levels in populations with preexisting cardiovascular disease. CLINICAL
      TRIAL REGISTRATION- clinicaltrials.gov. Identifier: TNT, NCT00327691; IDEAL,
      NCT00159835.

PMID- 20130233
TI  - Professional knowledge of child support staff: evidence from the New Jersey child
      support training program.
AB  - Child support enforcement (CSE) has experienced dramatic changes in the last
      decade; however, it is not clear whether child support staff is fully aware of
      the development. Using data from the New Jersey child support training program (n
      = 530), this article aims to evaluate the professional knowledge of child support
      staff. The results show that participants answered 55% of the questions on CSE
      correctly in the pretraining assessment. After the training, the participants
      answered 77% of all questions correctly. The findings reveal an urgent need for
      training for child support staff in a rapidly changing profession.

PMID- 20130234
TI  - Aggregate versus individual-level sexual behavior assessment: how much detail is
      needed to accurately estimate HIV/STI risk?
AB  - The sexual behaviors of HIV/sexually transmitted infection (STI) prevention
      intervention participants can be assessed on a partner-by-partner basis: in
      aggregate (i.e., total numbers of sex acts, collapsed across partners) or using a
      combination of these two methods (e.g., assessing five partners in detail and any
      remaining partners in aggregate). There is a natural trade-off between the level
      of sexual behavior detail and the precision of HIV/STI acquisition risk
      estimates. The results of this study indicate that relatively simple aggregate
      data collection techniques suffice to adequately estimate HIV risk. For highly
      infectious STIs, in contrast, accurate STI risk assessment requires more
      intensive partner-by-partner methods.

PMID- 20130235
TI  - Finding needles in a haystack: a methodology for identifying and sampling
      community-based youth smoking cessation programs.
AB  - BACKGROUND: Surveys of community-based programs are difficult to conduct when
      there is virtually no information about the number or locations of the programs
      of interest. This article describes the methodology used by the Helping Young
      Smokers Quit (HYSQ) initiative to identify and profile community-based youth
      smoking cessation programs in the absence of a defined sample frame. METHODS: We
      developed a two-stage sampling design, with counties as the first-stage
      probability sampling units. The second stage used snowball sampling to
      saturation, to identify individuals who administered youth smoking cessation
      programs across three economic sectors in each county. Multivariate analyses
      modeled the relationship between program screening, eligibility, and response
      rates and economic sector and stratification criteria. Cumulative logit models
      analyzed the relationship between the number of contacts in a county and the
      number of programs screened, eligible, or profiled in a county. RESULTS: The
      snowball process yielded 9,983 unique and traceable contacts. Urban and high
      income counties yielded significantly more screened program administrators; urban
      counties produced significantly more eligible programs, but there was no
      significant association between the county characteristics and program response
      rate. There is a positive relationship between the number of informants initially
      located and the number of programs screened, eligible, and profiled in a county.
      DISCUSSION: Our strategy to identify youth tobacco cessation programs could be
      used to create a sample frame for other nonprofit organizations that are
      difficult to identify due to a lack of existing directories, lists, or other
      traditional sample frames.

PMID- 20130236
TI  - Title IX, girls' sports participation, and adult female physical activity and
      weight.
AB  - Arguably, the most important school-based intervention to increase physical
      activity was Title IX of the Education Amendments of 1972, which led to a 600%
      increase in girls' sports participation between 1972 and 1978. We studied the
      effect of this increase in sports participation and athletic opportunities while
      young on the physical activity and weight of adult women some 20-25 years later.
      Our results indicate that adult women who were affected by Title IX and had
      greater opportunity to participate in athletics while young had lower body mass
      index (BMI) and lower rates of obesity and reported being more physically active
      than women who were not afforded these opportunities. However, effect sizes were
      quite modest.

PMID- 20130237
TI  - The post sepsis-induced expansion and enhanced function of regulatory T cells
      create an environment to potentiate tumor growth.
AB  - One of the more insidious outcomes of patients who survive severe sepsis is
      profound immunosuppression. In this study, we addressed the hypothesis that post
      septic immune defects were due, in part, to the presence and/or expansion of
      regulatory T cells (Tregs). After recovery from severe sepsis, mice exhibited
      significantly higher numbers of Tregs, which exerted greater in vitro suppressive
      activity compared with controls. The expansion of Tregs was not limited to
      CD25(+) cells, because Foxp3 expression was also detected in CD25(-) cells from
      post septic mice. This latter group exhibited a significant increase of chromatin
      remodeling at the Foxp3 promoter, because a marked increase in acetylation at
      H3K9 was associated with an increase in Foxp3 transcription. Post septic splenic
      dendritic cells promoted Treg conversion in vitro. Using a solid tumor model to
      explore the function of Tregs in an in vivo setting, we found post septic mice
      showed an increase in tumor growth compared with sham-treated mice with a
      syngeneic tumor model. This observation could mechanistically be related to the
      ability of post septic Tregs to impair the antitumor response mediated by CD8(+)
      T cells. Together, these data show that the post septic immune system obstructs
      tumor immunosurveillance, in part, by augmented Treg expansion and function.

PMID- 20130238
TI  - Critical roles for c-Myb in lymphoid priming and early B-cell development.
AB  - c-Myb is a transcription factor with functions in many hematopoietic lineages. c
      Myb-deficient mice display reduced numbers of B cells; however, it is unknown
      what role c-Myb plays in B lymphopoiesis because no critical target genes have
      been identified in the B-cell lineage. We demonstrate that conditional deletion
      of c-Myb in B-cell progenitors completely abolishes B-cell development. c-Myb is
      required for lymphoid progenitors to respond to the cytokines interleukin-7 and
      thymic stromal lymphopoietin; in the absence of sufficient c-Myb activity, mice
      display a B lymphopenia that closely resembles that observed in interleukin-7
      receptor alpha-deficient animals. Analysis of the multipotent progenitor
      compartment indicates that c-Myb is also required for up-regulation of multiple
      lymphoid-associated genes, including Il7r, and for the subsequent development of
      the common lymphoid progenitor population. These data show that c-Myb plays a
      critical role in the regulatory pathways governing lymphoid specification and
      early B-cell differentiation.

PMID- 20130239
TI  - Leukemogenic transformation by HOXA cluster genes.
AB  - HOX homeobox genes are important regulators of normal and malignant
      hematopoiesis. Abdominal-type HOXA genes like HOXA9 are highly leukemogenic.
      However, little is known about transformation by anterior HOXA genes. Here we
      performed a comprehensive assessment of the oncogenic potential of every HOXA
      gene in primary hematopoietic cells. With exception of HOXA2 and HOXA5, all HOXA
      genes caused a block or delay of hematopoietic differentiation and cooperated
      with Meis1. No evidence for the alleged tumor-suppressor function of HOXA5 could
      be found. Whereas all active HOXA genes immortalized mixed granulocytic/monocytic
      populations, HOXA13 preferentially specified monocytoid development. The anterior
      HOXA genes HOXA1, HOXA4, and HOXA6 transformed cells, generating permanent cell
      lines, although they did so less potently than HOXA9. Upon transplantation these
      lines induced myeloproliferation and acute myeloid leukemia in recipient animals.
      Kinetic studies with inducible HOX derivatives demonstrated that anterior HOXA
      genes autonomously contributed to cellular transformation. This function was not
      mediated by endogenous Hoxa9, which was persistently expressed in cells
      transformed by anterior HOX genes. In summary our results demonstrate a hitherto
      unexpected role of anterior HOXA genes in hematopoietic malignancy.

PMID- 20130240
TI  - Impaired NK-cell migration in WAS/XLT patients: role of Cdc42/WASp pathway in the
      control of chemokine-induced beta2 integrin high-affinity state.
AB  - We analyzed the involvement of Wiskott-Aldrich syndrome protein (WASp), a
      critical regulator of actin cytoskeleton remodeling, in the control of natural
      killer (NK)-cell migration. NK cells derived from patients with Wiskott-Aldrich
      syndrome/X-linked thrombocytopenia (WAS/XLT), carrying different mutations in the
      WASP coding gene, displayed reduced migration through intercellular adhesion
      molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), or endothelial
      cells in response to CXCL12/stromal cell-derived factor-1 and CX3CL1/fractalkine.
      Inhibition of WAS/XLT NK-cell migration was associated with reduced ability of
      these cells to up-regulate the expression of CD18 activation neoepitope and to
      adhere to ICAM-1 or VCAM-1 following chemokine stimulation. Moreover, chemokine
      receptor or beta1 or beta2 integrin engagement on NK cells rapidly resulted in
      Cdc42 activation and WASp tyrosine phosphorylation as well as in WASp association
      with Fyn and Pyk-2 tyrosine kinases. NK-cell pretreatment with wiskostatin, to
      prevent Cdc42/WASp association, impaired chemokine-induced NK-cell migration
      through ICAM-1 and beta2 integrin activation-dependent neoepitope expression.
      These results show that the Cdc42/WASp pathway plays a crucial role in the
      regulation of NK-cell migration by acting as a critical component of the
      chemokine-induced inside-out signaling that regulates lymphocyte function
      associated antigen-1 function and suggest that after integrin or chemokine
      receptor engagement WASp function is regulated by the coordinate action of both
      Cdc42 and tyrosine kinases.

PMID- 20130241
TI  - Dexamethasone plus rituximab yields higher sustained response rates than
      dexamethasone monotherapy in adults with primary immune thrombocytopenia.
AB  - Previous observational studies suggest that rituximab may be useful in the
      treatment of primary immune thrombocytopenia (ITP). This randomized trial
      investigated rituximab efficacy in previously untreated adult ITP patients with a
      platelet count of 20 x 10(9)/L or less. One hundred three patients were randomly
      assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m(2)
      rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone
      received salvage therapy with dexamethasone plus rituximab. Sustained response
      (ie, platelet count > or = 50 x 10(9)/L at month 6 after treatment initiation),
      evaluable in 101 patients, was greater in patients treated with dexamethasone
      plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52;
      63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in
      the experimental arm showed increased incidences of grade 3 to 4 adverse events
      (10% vs 2%, P = .082, 95% CI, -0.010 to 0.175), but incidences of serious adverse
      events were similar in both arms (6% vs 2%, P = .284, 95% CI, -0.035 to 0.119).
      Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients
      refractory to dexamethasone. The combination of dexamethasone and rituximab
      improved platelet counts compared with dexamethasone alone. Thus, combination
      therapy may represent an effective treatment option before splenectomy. This
      study is registered at http://clinicaltrials.gov as NCT00770562.

PMID- 20130242
TI  - Targeting human telomerase reverse transcriptase with recombinant lentivector is
      highly effective to stimulate antitumor CD8 T-cell immunity in vivo.
AB  - The success of active immunotherapy is based on the vaccine's ability to overcome
      immune tolerance through recalibrating the immune system so that it is able to
      recognize tumor antigens as foreign rather than self. In this study, we used a
      lentiviral vector system to target human telomerase reverse transcriptase (lv
      hTERT), a widely expressed tumor antigen. Immunization of HLA-A*0201 transgenic
      HHD mice with recombinant lv-hTERT vector induces potent and diversified
      cytotoxic T lymphocyte responses that recognize in vitro murine tumor cells,
      which overexpress telomerase. Compared with peptide-based vaccinations, the lv
      hTERT vector triggers better and more sustained CD8(+) T-cell response against
      self/TERT epitope in vivo. The study found that the additional use of a
      heterologous boosted vaccination drastically improves self/TERT-specific CD8
      responses in lv-hTERT primed mice. Both primary and long-lasting self/TERT
      specific CD8(+) T-cell responses induced with Iv-hTERT vector required the
      presence of CD4 T cells in vivo. This lv-hTERT-based active immunotherapy
      efficiently inhibits the growth of telomerase expressing tumors (B16/HLA-A2.1
      murine melanoma) in HHD mice. These data show that targeting hTERT with
      lentivector is highly effective in stimulating a broad range of CD8 T-cell
      immunity that can be exploited for cancer immunotherapy.

PMID- 20130243
TI  - Preclinical characterization of the selective JAK1/2 inhibitor INCB018424:
      therapeutic implications for the treatment of myeloproliferative neoplasms.
AB  - Constitutive JAK2 activation in hematopoietic cells by the JAK2V617F mutation
      recapitulates myeloproliferative neoplasm (MPN) phenotypes in mice, establishing
      JAK2 inhibition as a potential therapeutic strategy. Although most polycythemia
      vera patients carry the JAK2V617F mutation, half of those with essential
      thrombocythemia or primary myelofibrosis do not, suggesting alternative
      mechanisms for constitutive JAK-STAT signaling in MPNs. Most patients with
      primary myelofibrosis have elevated levels of JAK-dependent proinflammatory
      cytokines (eg, interleukin-6) consistent with our observation of JAK1
      hyperactivation. Accordingly, we evaluated the effectiveness of selective JAK1/2
      inhibition in experimental models relevant to MPNs and report on the effects of
      INCB018424, the first potent, selective, oral JAK1/JAK2 inhibitor to enter the
      clinic. INCB018424 inhibited interleukin-6 signaling (50% inhibitory
      concentration [IC(50)] = 281nM), and proliferation of JAK2V617F(+) Ba/F3 cells
      (IC(50) = 127nM). In primary cultures, INCB018424 preferentially suppressed
      erythroid progenitor colony formation from JAK2V617F(+) polycythemia vera
      patients (IC(50) = 67nM) versus healthy donors (IC(50) > 400nM). In a mouse model
      of JAK2V617F(+) MPN, oral INCB018424 markedly reduced splenomegaly and
      circulating levels of inflammatory cytokines, and preferentially eliminated
      neoplastic cells, resulting in significantly prolonged survival without
      myelosuppressive or immunosuppressive effects. Preliminary clinical results
      support these preclinical data and establish INCB018424 as a promising oral agent
      for the treatment of MPNs.

PMID- 20130245
TI  - Surgeons' dispatch from Cange, Haiti.

PMID- 20130244
TI  - The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense
      rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma.
AB  - This is a phase 2 study to assess the role of tumor histogenesis (subtype),
      fluorodeoxyglucose positron emission tomography (FDG-PET), and short-course
      etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with dose
      dense rituximab (SC-EPOCH-RR) in newly diagnosed HIV-associated CD20(+) diffuse
      large B-cell lymphoma. Patients received a minimum of 3 and a maximum of 6 cycles
      with 1 cycle beyond stable radiographic and FDG-PET scans. Overall, 79% of
      patients received 3 cycles. Combination antiretroviral therapy was suspended
      before and resumed after therapy. Thirty-three enrolled patients had a median age
      of 42 years (range, 9-61 years), and 76% had a high-intermediate or high age
      adjusted international prognostic index. At 5 years median follow-up, progression
      free and overall survival were 84% and 68%, respectively. There were no treatment
      related deaths or new opportunistic infections during treatment, and patients had
      sustained CD4 cell count recovery and HIV viral control after treatment. FDG-PET
      after 2 cycles had an excellent negative but poor positive predictive value.
      Tumor histogenesis was the only characteristic associated with lymphoma-specific
      outcome with 95% of germinal center B-cell (GCB) versus 44% of non-GCB diffuse
      large B-cell lymphoma (DLBCL) progression-free at 5 years. SC-EPOCH-RR is highly
      effective and less immunosuppressive with shorter duration therapy compared with
      standard strategies. However, new therapeutic advances are needed for non-GCB
      DLBCL, which remains the important cause of lymphoma-specific death. This trial
      was registered at www.clinicaltrials.gov as NCT000019253.

PMID- 20130246
TI  - Risking big changes with small reforms.

PMID- 20130247
TI  - Coordinating and prioritizing aid in Haiti.

PMID- 20130248
TI  - Cogito ergo sum by MRI.

PMID- 20130249
TI  - Giving teeth to comparative-effectiveness research--the Oregon experience.

PMID- 20130250
TI  - Willful modulation of brain activity in disorders of consciousness.
AB  - BACKGROUND: The differential diagnosis of disorders of consciousness is
      challenging. The rate of misdiagnosis is approximately 40%, and new methods are
      required to complement bedside testing, particularly if the patient's capacity to
      show behavioral signs of awareness is diminished. METHODS: At two major referral
      centers in Cambridge, United Kingdom, and Liege, Belgium, we performed a study
      involving 54 patients with disorders of consciousness. We used functional
      magnetic resonance imaging (MRI) to assess each patient's ability to generate
      willful, neuroanatomically specific, blood-oxygenation-level-dependent responses
      during two established mental-imagery tasks. A technique was then developed to
      determine whether such tasks could be used to communicate yes-or-no answers to
      simple questions. RESULTS: Of the 54 patients enrolled in the study, 5 were able
      to willfully modulate their brain activity. In three of these patients,
      additional bedside testing revealed some sign of awareness, but in the other two
      patients, no voluntary behavior could be detected by means of clinical
      assessment. One patient was able to use our technique to answer yes or no to
      questions during functional MRI; however, it remained impossible to establish any
      form of communication at the bedside. CONCLUSIONS: These results show that a
      small proportion of patients in a vegetative or minimally conscious state have
      brain activation reflecting some awareness and cognition. Careful clinical
      examination will result in reclassification of the state of consciousness in some
      of these patients. This technique may be useful in establishing basic
      communication with patients who appear to be unresponsive.

PMID- 20130251
TI  - Images in clinical medicine. Bleeding esophageal varices.

PMID- 20130252
TI  - Withholding information from patients--when less is more.

PMID- 20130253
TI  - Clinical practice. Jet lag.

PMID- 20130254
TI  - Images in clinical medicine. Kinked carotids.

PMID- 20130255
TI  - Clinical problem-solving. Under pressure.

PMID- 20130257
TI  - Intensity of continuous renal-replacement therapy.

PMID- 20130258
TI  - Functional status of elderly adults receiving dialysis.

PMID- 20130259
TI  - Ankle-brachial index and peripheral arterial disease.

PMID- 20130260
TI  - Accuracy of financial disclosures reported by physicians.

PMID- 20130261
TI  - Transfusion of RhD-positive blood in "Asia type" DEL recipients.

PMID- 20130262
TI  - A Wii fracture.

PMID- 20130263
TI  - Lack of functional pregnancy-associated plasma protein-A (PAPPA) compromises
      mouse ovarian steroidogenesis and female fertility.
AB  - The insulin-like growth factor (IGF) system plays an important role in regulating
      ovarian follicular development and steroidogenesis. IGF binding proteins (IGFBP)
      mostly inhibit IGF actions, and IGFBP proteolysis is a major mechanism for
      regulating IGF bioavailability. Pregnancy-associated plasma protein-A (PAPPA) is
      a secreted metalloprotease responsible for cleavage of IGFBP4 in the ovary. The
      aim of this study was to investigate whether PAPPA plays a role in regulating
      ovarian functions and female fertility by comparing the reproductive phenotype of
      wild-type (WT) mice with mice heterozygous or homozygous for a targeted Pappa
      gene deletion (heterozygous and PAPP-A knockout [KO] mice, respectively). When
      mated with WT males, PAPP-A KO females demonstrated an overall reduction in
      average litter size. PAPP-A KO mice had a reduced number of ovulated oocytes,
      lower serum estradiol levels following equine chorionic gonadotropin
      administration, lower serum progesterone levels after human chorionic
      gonadotropin injection, and reduced expression of ovarian steroidogenic enzyme
      genes, compared to WT controls. In PAPP-A KO mice, inhibitory IGFBP2, IGFBP3, and
      IGFBP4 ovarian gene expression was reduced postgonadotropin stimulation,
      suggesting some compensation within the ovarian IGF system. Expression levels of
      follicle-stimulating hormone receptor, luteinizing hormone receptor, and genes
      required for cumulus expansion were not affected. Analysis of preovulatory
      follicular fluid showed complete loss of IGFBP4 proteolytic activity in PAPP-A KO
      mice, demonstrating no compensation for loss of PAPPA proteolytic activity by
      other IGFBP proteases in vivo in the mouse ovary. Taken together, these data
      demonstrate an important role of PAPPA in modulating ovarian function and female
      fertility by control of the bioavailability of ovarian IGF.

PMID- 20130265
TI  - Fine tuning of endometrial function by estrogen and progesterone through
      microRNAs.

PMID- 20130264
TI  - Constitutive activation of smoothened leads to female infertility and altered
      uterine differentiation in the mouse.
AB  - Previous work has identified Indian hedgehog (Ihh) as a major mediator of
      progesterone signaling during embryo implantation. Ihh acts through its
      downstream effector smoothened (Smo) to activate the GLI family of transcription
      factors. In order to gain a better understanding of Ihh action during embryo
      implantation, we expressed a Cre-recombinase-dependent constitutively activated
      SMO in the murine uterus using the Pgr(tm2(cre)Lyd) (PR(cre)) mouse model
      [Pgr(tm2(cre)Lyd+)Gt(ROSA)26Sor(tm1(Smo/EYFP)Amc)(+) (PR(cre/+)SmoM2(+))]. Female
      PR(cre/+)SmoM2(+) mice were infertile. They exhibited normal serum progesterone
      levels and normal ovulation, but their ova failed to be fertilized in vivo and
      their uterus failed to undergo the artificially induced decidual response.
      Examination of the PR(cre/+)SmoM2(+) uteri revealed numerous features such as
      uterine hypertrophy, the presence of a stratified luminal epithelial cell layer,
      a reduced number of uterine glands, and an endometrial stroma that had lost its
      normal morphologic characteristics. Microarray analysis of 3-mo-old
      PR(cre/+)SmoM2(+) uteri demonstrated a chondrocytic signature and confirmed that
      constitutive activation of PR(cre/+)SmoM2(+) increased extracellular matrix
      production. Thus, constitutive activation of Smo in the mouse uterus alters
      postnatal uterine differentiation which interferes with early pregnancy. These
      results provide new insight into the role of Hedgehog signaling during embryo
      implantation.

PMID- 20130266
TI  - Epididymal hypo-osmolality induces abnormal sperm morphology and function in the
      estrogen receptor alpha knockout mouse.
AB  - Estrogen receptor-alpha (ESR1) is highly expressed in the efferent ductules of
      all species studied as well as in the epididymal epithelium in mice and other
      select species. Male mice lacking ESR1 (Esr1KO) are infertile, but
      transplantation studies demonstrated that Esr1KO germ cells are capable of
      fertilization when placed in a wild-type reproductive tract. These results
      suggest that extratesticular regions, such as the efferent ductules and
      epididymis, are the major source of pathological changes in Esr1KO males.
      Previous studies have shown alterations in ion and fluid transporters in the
      efferent duct and epididymal epithelia of Esr1KO males, leading to misregulation
      of luminal fluid pH. To determine the effect of an altered epididymal milieu on
      Esr1KO sperm, we assayed sperm morphology in the different regions of the
      epididymis. Sperm recovered from the epididymis exhibited abnormal flagellar
      coiling and increased incidence of spontaneous acrosome reactions, both of which
      are consistent with exposure to abnormal epididymal fluid. Analysis of the
      epididymal fluid revealed that the osmolality of the Esr1KO fluid was reduced
      relative to wild type, consistent with prior reports of inappropriate fluid
      absorption from the efferent ductules. This, along with the finding that
      morphological defects increased with transit through the epididymal duct,
      suggests that the anomalies in sperm are a consequence of the abnormal luminal
      environment. Consistent with this, incubating Esr1KO sperm in a more wild-type
      like osmotic environment significantly rescued the abnormal flagellar coiling.
      This work demonstrates that Esr1KO mice exhibit an abnormal fluid environment in
      the lumen of the efferent ducts and epididymis, precluding normal sperm
      maturation and instead resulting in progressive deterioration of sperm that
      contributes to infertility.

PMID- 20130267
TI  - Absence of estrogen receptor alpha leads to physiological alterations in the
      mouse epididymis and consequent defects in sperm function.
AB  - Male mice deficient in ESR1 (ERalpha) (Esr1KO mice) are infertile, and sperm
      recovered from the cauda epididymis exhibit reduced motility and fail to
      fertilize eggs in vitro. These effects on sperm appear to result from defective
      epididymal function and not a direct effect on spermatogenesis, as Esr1KO germ
      cells transplanted into wild-type testes yield normal offspring. We hypothesized
      that the previously described defect in efferent duct fluid reabsorption would
      lead to alterations in the epididymal fluid milieu, which would negatively impact
      sperm function. Analysis of the epididymal fluid revealed that the Esr1KO
      maintains a higher luminal pH throughout the epididymis, confirming an inability
      of the efferent ducts and/or epididymis to properly acidify the luminal contents.
      Subsequent studies showed that these abnormalities were not the result of global
      defects in epididymal function since protein secretion by the Esr1KO epididymis
      appeared normal as judged by SDS-PAGE of total secreted proteins and by
      immunoblotting of candidate secreted proteins. To gain insight into the basis of
      the aberrant fluid homeostasis in the Esr1KO epididymis, the expression of
      several enzymes and transporters known to be involved in acid/base regulation
      were analyzed. The levels of SLC9A3 (NHE3) as well as carbonic anhydrase XIV and
      SLC4A4 (NBC1) were all reduced in the proximal portion of the Esr1KO epididymis,
      while other components appeared unaffected, including other ion transporters and
      ATP6V0A1 (V-ATPase). The altered luminal milieu of the Esr1KO epididymis was
      shown to lead to a corresponding increase in the intracellular pH of Esr1KO
      sperm, relative to sperm from control animals. Since pH and bicarbonate ions are
      critical regulators of sperm cAMP levels and motility, we attempted to bypass the
      abnormal luminal and intracellular environment by supplementing sperm with
      exogenous cAMP. This treatment rescued all defective motility parameters, as
      assayed by CASA, further showing that motility defects are not intrinsic to the
      sperm but, rather, result from the abnormal epididymal milieu.

PMID- 20130268
TI  - USP8, a regulator of endosomal sorting, is involved in mouse acrosome biogenesis
      through interaction with the spermatid ESCRT-0 complex and microtubules.
AB  - Ubiquitin-specific peptidase 8 (USP8) is a deubiquitinating enzyme that works as
      a regulator of endosomal sorting and vesicle morphology in cultured cells. Its
      function in vivo is, however, unknown as USP8 gene deletion leads to embryonic
      lethality. Previously, we have shown that USP8 is highly expressed in male germ
      cells. These cells develop a peculiar acidic vesicle that is indispensable for
      fertilization, the acrosome; USP8 might be involved in vivo in acrosomogenesis.
      The objective of this study was to test this hypothesis by determining if
      selective components of the early endosomal machinery interact functionally with
      USP8 during acrosomogenesis using protein-protein interaction assays and
      double/triple immunolabeling. Moreover, by exploiting the characteristic of USP8
      that exhibits a microtubule interacting and trafficking/transport (MIT) domain,
      we verified whether USP8 effectively associates with spermatid microtubules by
      microtubule cosedimentation and binding assays. USP8 was able to interact with
      spermatid ESCRT-0 (endosomal-sorting complex required for transport-0) and
      microtubule structures; USP8/ESCRT-0-labeled vesicles, monitored by fluorescence
      microscopy, were found to contribute to acrosome formation while USP8 can
      directly link, via its MIT domain, the labeled vesicles/developing acrosome to
      microtubules, which could favor both acrosome assembly and shaping. VPS54, the
      vacuolar-sorting protein responsible for early endocytic retrograde transport,
      was here detected for the first time in male germ cells; VPS54 followed the
      intracellular route of USP8/ESCRT-0-labeled vesicles during acrosomogenesis. We
      concluded that in vivo USP8 has a role strongly associated with acrosome
      biogenesis and that the early endosome pathway is significantly involved in the
      process, which suggests that the acrosome could be a novel lysosome-related
      organelle.

PMID- 20130269
TI  - The role of mitochondrial DNA copy number in mammalian fertility.
AB  - Mammalian mitochondrial DNA (mtDNA) is a small, maternally inherited genome that
      codes for 13 essential proteins in the respiratory chain. Mature oocytes contain
      more than 150 000 copies of mtDNA, at least an order of magnitude greater than
      the number in most somatic cells, but sperm contain only approximately 100
      copies. Mitochondrial oxidative phosphorylation has been suggested to be an
      important determinant of oocyte quality and sperm motility; however, the
      functional significance of the high mtDNA copy number in oocytes, and of the low
      copy number in sperm, remains unclear. To investigate the effects of mtDNA copy
      number on fertility, we genetically manipulated mtDNA copy number in the mouse by
      deleting one copy of Tfam, an essential component of the mitochondrial nucleoid,
      at different stages of germline development. We show that males can tolerate at
      least a threefold reduction in mtDNA copy number in their sperm without impaired
      fertility, and in fact, they preferentially transmit a deleted Tfam allele.
      Surprisingly, oocytes with as few as 4000 copies of mtDNA can be fertilized and
      progress normally through preimplantation development to the blastocyst stage.
      The mature oocyte, however, has a critical postimplantation developmental
      threshold of 40 000-50 000 copies of mtDNA in the mature oocyte. These
      observations suggest that the high mtDNA copy number in the mature oocyte is a
      genetic device designed to distribute mitochondria and mtDNAs to the cells of the
      early postimplantation embryo before mitochondrial biogenesis and mtDNA
      replication resumes, whereas down-regulation of mtDNA copy number is important
      for normal sperm function.

PMID- 20130270
TI  - Activin bioactivity affects germ cell differentiation in the postnatal mouse
      testis in vivo.
AB  - The transforming growth factor beta superfamily ligand activin A controls
      juvenile testis growth by stimulating Sertoli cell proliferation. Testicular
      levels are highest in the first postnatal week, when Sertoli cells are
      proliferating and spermatogonial stem cells first form. Levels decrease sharply
      as Sertoli cell proliferation ceases and spermatogenic differentiation begins. We
      hypothesized that changing activin levels also affect germ cell maturation. We
      detected an acute and developmentally regulated impact of activin on Kit mRNA in
      cocultures of Sertoli cells and germ cells from Day 8, but not Day 4, mice. Both
      stereological and flow cytometry analyses identified an elevated
      spermatogonium:Sertoli cell ratio in Day 7 testes from Inhba(BK/BK) mice, which
      have decreased bioactive activin, and the germ cell markers Sycp3, Dazl, and
      Ccnd3 were significantly elevated in Inhba(BK/BK) mice. The flow cytometry
      measurements demonstrated that surface KIT protein is significantly higher in Day
      7 Inhba(BK/BK) germ cells than in wild-type littermates. By Day 14, the germ
      cell:Sertoli cell ratio did not differ between genotypes, but the transition of
      type A spermatogonia into spermatocytes was altered in Inhba(BK/BK) testes. We
      conclude that regulated activin signaling not only controls Sertoli cell
      proliferation, as previously described, but also influences the in vivo
      progression of germ cell maturation in the juvenile testis at the onset of
      spermatogenesis.

PMID- 20130272
TI  - A novel nonsense mutation in CEP290 induces exon skipping and leads to a
      relatively mild retinal phenotype.
AB  - PURPOSE. To identify the genetic defect in a family with variable retinal
      phenotypes. The proband had a diagnosis of Leber congenital amaurosis (LCA),
      whereas her two cousins had an early-onset severe retinal dystrophy (EOSRD) with
      useful vision. A distant family member had retinitis pigmentosa (RP). METHODS.
      DNA samples of the affected family members were genotyped with 250 K genome-wide
      SNP microarrays. Genetic defects were localized by linkage analysis and
      homozygosity mapping, and candidate genes were analyzed by sequencing. Patients
      underwent a full ophthalmic examination. RESULTS. Compound heterozygous mutations
      in CEP290 were identified in the proband and her two cousins: the frequent
      c.2991+1655A>G founder mutation and a novel nonsense mutation in exon 7
      (c.451C>T, p.Arg151X). The proband had nystagmus, hyperopia, a flat
      electroretinogram (ERG), and decreased visual acuity (20/250) from birth. The two
      cousins had minimal scotopic ERG responses at the age of 2. In one of these
      patients, visual acuity had reached a level of 20/32 at age 5, which is high for
      patients with CEP290 mutations. Analysis of the CEP290 mRNA in affected
      individuals revealed altered splice forms in which either exon 7 or exons 7 and 8
      were skipped. In both mutant cDNA products, the open reading frame was not
      disrupted. Furthermore, homozygosity mapping and mutation analysis in the distant
      family member affected by RP revealed a homozygous mutation in MERTK, but no
      CEP290 mutations. This MERTK mutation was heterozygously present in the most
      severely affected (LCA) patient, but was absent in the two more mildly affected
      cousins. CONCLUSIONS. A novel nonsense mutation in CEP290 results in nonsense
      associated altered splicing. That the remaining open reading frame is intact may
      explain the less severe phenotype observed in the two affected cousins. The
      additional heterozygous mutation in MERTK may clarify the more severe phenotype
      in the proband. This study extends the phenotypic spectrum of CEP290-associated
      diseases at the mild end.

PMID- 20130271
TI  - Function-specific intracellular signaling pathways downstream of heparin-binding
      EGF-like growth factor utilized by human trophoblasts.
AB  - Heparin-binding EGF-like growth factor (HBEGF) is expressed by trophoblast cells
      throughout gestation. First-trimester cytotrophoblast cells are protected from
      hypoxia-induced apoptosis because of the accumulation of HBEGF through a
      posttranscriptional autocrine mechanism. Exogenous application of HBEGF is
      cytoprotective in a hypoxia/reoxygenation (H/R) injury model and initiates
      trophoblast extravillous differentiation to an invasive phenotype. The downstream
      signaling pathways induced by HBEGF that mediate these various cellular
      activities were identified using two human first-trimester cytotrophoblast cell
      lines, HTR-8/SVneo and SW.71, with similar results. Recombinant HBEGF (1 nM)
      induced transient phosphorylation of MAPK3/1 (ERK), MAPK14 (p38), and AKT within
      15 min and JNK after 1-2 h. To determine which downstream pathways regulate the
      various functions of HBEGF, cells were treated with specific inhibitors of the
      ERK upstream regulator MEK (U0126), the AKT upstream regulator phosphoinositide-3
      (PI3)-kinase (LY294002), MAPK14 (SB203580), and JNK (SP600125), as well as with
      inactive structural analogues. Only SB203580 specifically prevented HBEGF
      mediated rescue during H/R, while each inhibitor attenuated HBEGF-stimulated cell
      migration. Accumulation of HBEGF at reduced oxygen was blocked only by a
      combination of U0126, SB203580, and SP600125. We conclude that HBEGF advances
      trophoblast extravillous differentiation through coordinate activation of PI3
      kinase, ERK, MAPK14, and JNK, while only MAPK14 is required for its antiapoptotic
      activity. Additionally, hypoxia induces an autocrine increase in HBEGF protein
      levels through MAPK14, JNK or ERK. These experiments reveal a complexity of the
      intracellular signaling circuitry that regulates trophoblast functions critical
      for implantation and placentation.

PMID- 20130273
TI  - Inhibition of matrix metalloproteinase activity in the chick sclera and its
      effect on myopia development.
AB  - PURPOSE: To investigate the contribution of matrix degradation in the two-layer
      avian sclera to the development of myopia. METHODS: Tissue inhibitor of
      metalloproteinase-2 (TIMP-2) was used to inhibit chick scleral collagen
      degradation with (3)H-proline, a marker for this effect. Ex vivo scleral culture
      experiments confirmed TIMP-2 doses for in vivo experimentation. Ocular growth and
      refractive response to exogenous TIMP-2 (11.25, 2.25, and 0.45 picomoles, plus
      vehicle only) were monitored in 7-day-old chicks during the induction of myopia
      over 4 days with a translucent occluder. Collagen degradation was assessed, in
      whole sclera and in separated scleral layers by using the same paradigm (11.25
      picomoles TIMP-2; vehicle only). RESULTS: Approximately 60% of collagen
      degradation was inhibited with low (2 nM) doses of TIMP-2 in the ex vivo sclera.
      Degradative activity in the in vivo chick sclera increased significantly (46%)
      during myopia development, with all the altered activity confined to the fibrous
      layer. Addition of TIMP-2 significantly reduced (by 46%) this accelerated scleral
      collagen degradation, also by acting in the fibrous layer. TIMP-2 had no
      significant effect on (3)H-proline incorporated in the cartilaginous scleral
      layer and cornea. Despite inhibiting collagen degradation TIMP-2 had no
      significant effect on myopia development. CONCLUSIONS: Increased collagen
      degradation is a feature of scleral remodeling in chick myopia development, but
      is confined to the fibrous scleral layer. Significant inhibition of this
      collagenolytic activity with TIMP-2 has little effect on refractive error
      development, suggesting that collagen degradation in the sclera contributes
      little to the development of myopia in the chick.

PMID- 20130274
TI  - Growth factor signaling in vitreous humor-induced lens fiber differentiation.
AB  - PURPOSE. Although some of the factors and signaling pathways that are involved in
      induction of fiber differentiation have been defined, such as FGF-mediated
      MAPK/ERK and PI3-K/Akt signaling, the factors in the vitreous that regulate this
      differentiation process in vivo have yet to be identified. The purpose of this
      study was to better understand the role of growth factors in vitreous that
      regulate this process by further characterizing the signaling pathways involved
      in lens fiber differentiation. METHODS. Rat lens epithelial explants were used to
      compare the ability of vitreous, IGF-1, PDGF-A, EGF, and FGF-2 to stimulate the
      phosphorylation of ERK1/2 and Akt leading to fiber differentiation, in the
      presence or absence of selective receptor tyrosine kinase (RTK) inhibitors.
      RESULTS. Similar to vitreous, FGF induced a sustained ERK1/2 signaling profile,
      unlike IGF, PDGF, and EGF, which induced a more transient (shorter) activation of
      ERK1/2. For Akt activation, IGF was the only factor that induced a profile
      similar to vitreous. IGF, PDGF, and EGF potentiated the effects of a low dose of
      FGF on lens fiber differentiation by extending the duration of ERK1/2
      phosphorylation. In the presence of selective RTK inhibitors, although the
      sustained vitreous-induced ERK1/2 signaling profile and subsequent fiber
      differentiation was perturbed, the results also showed that, although prolonged
      ERK1/2 phosphorylation was necessary, it was not sufficient for fiber
      differentiation to proceed. CONCLUSIONS. These results are consistent with FGF's
      being the key growth factor involved in vitreous-induced signaling leading to
      lens fiber differentiation; however, they also indicate that other vitreal growth
      factors such as IGF may be involved in fine-tuning ERK1/2- and Akt
      phosphorylation to the level that is necessary for initiation and/or maintenance
      of lens fiber differentiation in vivo.

PMID- 20130275
TI  - The impact of inoculation parameters on the pathogenesis of contact lens-related
      infectious keratitis.
AB  - PURPOSE: Contact lens wear predisposes to Pseudomonas aeruginosa keratitis, but
      the mechanisms involved remain unclear. An in vivo model was used to study lens
      inoculation conditions enabling disease. METHODS: Custom-made hydrogel contact
      lenses were fitted to rats after incubation in P. aeruginosa approximately 10(11)
      cfu/mL (3 hours) or approximately 10(3) cfu/mL (24 hours). Another group was
      inadvertently inoculated with a suction pen previously used with high inocula,
      but rinsed in ethanol and stored dry (6 months). Some corneas were tissue paper
      blotted to cause fluorescein staining before lens fitting. Contralateral eyes
      were untreated. Twenty-four hours after disease detection, lenses were
      transferred to naive rats or examined by confocal microscopy before
      homogenization to quantify viable bacteria. After lens removal, corneas were
      washed to collect nonadherent bacteria and were analyzed by immunohistochemistry.
      RESULTS: All eyes challenged with unworn contaminated lenses developed keratitis
      after approximately 7 to 10 days. Disease delay and severity were unaffected by
      inoculum parameters or tissue blotting but occurred sooner with lenses
      transferred from infected eyes ( approximately 2 days). Worn lenses and corneal
      washes contained infecting bacteria. Posterior, not anterior, lens surfaces
      harbored P. aeruginosa biofilms that penetrated the lens matrix. Diseased corneas
      showed an infiltration of phagocytes and T-lymphocytes. CONCLUSIONS: P.
      aeruginosa induces keratitis in this lens-wearing model after a single
      inoculation. Delayed disease onset was interesting considering the greater
      keratitis risk during extended wear. Infection did not require the disruption of
      corneal barrier function before lens wear and occurred without exposure to lens
      care solutions. The data suggest that keratitis involves biofilm formation or
      other bacterial adaptations in vivo.

PMID- 20130276
TI  - The mouse model of Down syndrome Ts65Dn presents visual deficits as assessed by
      pattern visual evoked potentials.
AB  - PURPOSE: The Ts65Dn mouse is the most complete widely available animal model of
      Down syndrome (DS). Quantitative information was generated about visual function
      in the Ts65Dn mouse by investigating their visual capabilities by means of
      electroretinography (ERG) and patterned visual evoked potentials (pVEPs).
      METHODS: pVEPs were recorded directly from specific regions of the binocular
      visual cortex of anesthetized mice in response to horizontal sinusoidal gratings
      of different spatial frequency, contrast, and luminance generated by a
      specialized video card and presented on a 21-in. computer display suitably
      linearized by gamma correction. RESULTS: ERG assessments indicated no significant
      deficit in retinal physiology in Ts65Dn mice compared with euploid control mice.
      The Ts65Dn mice were found to exhibit deficits in luminance threshold, spatial
      resolution, and contrast threshold, compared with the euploid control mice. The
      behavioral counterparts of these parameters are luminance sensitivity, visual
      acuity, and the inverse of contrast sensitivity, respectively. CONCLUSIONS: DS
      includes various phenotypes associated with the visual system, including deficits
      in visual acuity, accommodation, and contrast sensitivity. The present study
      provides electrophysiological evidence of visual deficits in Ts65Dn mice that are
      similar to those reported in persons with DS. These findings strengthen the role
      of the Ts65Dn mouse as a model for DS. Also, given the historical assumption of
      integrity of the visual system in most behavioral assessments of Ts65Dn mice,
      such as the hidden-platform component of the Morris water maze, the visual
      deficits described herein may represent a significant confounding factor in the
      interpretation of results from such experiments.

PMID- 20130277
TI  - Reduced connexin 43 expression and its effect on the development of vascular
      lesions in retinas of diabetic mice.
AB  - PURPOSE. To examine whether diabetes-induced connexin 43 downregulation promotes
      retinal vascular lesions characteristic of diabetic retinopathy (DR). METHODS.
      Two animal models, streptozotocin-induced diabetic mice and Cx43 heterozygous
      knockout (Cx43(+/-)) mice, were studied to directly assess whether diabetes
      reduces the expression of retinal Cx43, which, in turn, contributes to retinal
      vascular cell loss by apoptosis. Retinal Cx43 protein levels were assessed in
      nondiabetic control mice, diabetic mice, and Cx43(+/-) mice by Western blot
      analysis, and Cx43 localization and distribution in the retinal vascular cells
      were studied by immunostaining of retinal trypsin digests (RTDs). In parallel,
      RTDs were stained with hematoxylin and periodic acid Schiff to determine pericyte
      loss (PL) and acellular capillaries (AC), and TUNEL assays were performed to
      determine retinal vascular cell apoptosis. RESULTS. Western blot analysis
      indicated significant reductions in retinal Cx43 protein levels in diabetic mice
      and Cx43(+/-) mice compared with those of nondiabetic mice. Similarly, a
      significant reduction in Cx43 immunostaining was observed in the retinal
      capillaries of diabetic mice and Cx43(+/-) mice compared with those of control
      mice. Both diabetic and age-matched Cx43(+/-) mice exhibited increased amount of
      PL, AC, and TUNEL-positive cells compared with control mice. CONCLUSIONS.
      Diabetes-induced inhibition of Cx43 expression contributes to vascular cell
      apoptosis in retinas of diabetic mice. This suggests that reduced Cx43 expression
      plays a critical role in the development of AC and PL associated with DR.

PMID- 20130278
TI  - The relationship between demodex and ocular discomfort.
AB  - PURPOSE: To determine the correlative relationship between the prevalence of
      Demodex in eyelashes and the severity of ocular discomfort, by investigating the
      demographic epidemiology associated with Demodex. METHODS: One hundred seventy
      patients underwent epilation of four eyelashes of each eye, and the number of
      Demodex was counted. The patients answered questionnaires about ocular surface
      discomfort and underwent ophthalmic examinations, including slit lamp, tear film
      breakup time (BUT), Schirmer test, and microbial culturing. The correlative
      relationship between the number of Demodex and these variable data was analyzed.
      RESULTS: Demodex was found in 120 (70%) of the 170 tested patients. Of 1360
      eyelashes, 740 (54%) had Demodex. There was no significant difference in the
      prevalence of Demodex between males and females (P = 0.35). The number of Demodex
      showed significant positive correlations with increased age, ocular discomfort,
      and 1/BUT (P < 0.001), but not with the Schirmer scores. The number of Demodex
      was significantly higher in patients with conjunctival papillary hypertrophy than
      in those without (P = 0.003). The presence or distribution of bacteria on
      eyelashes was similar between eyelids with and without Demodex. However,
      methicillin-resistant Staphylococcus aureus (MRSA) was detected more often on
      eyelids with Demodex, but this difference was not statistically significant.
      CONCLUSIONS: There is a strong correlation between the number of Demodex and the
      severity of ocular discomfort, suggesting that Demodex plays a pathogenic role in
      the ocular discomfort linked with aging.

PMID- 20130279
TI  - Automated segmentation of foveal avascular zone in fundus fluorescein
      angiography.
AB  - PURPOSE. To describe and evaluate the performance of a computerized automated
      segmentation technique for use in quantification of the foveal avascular zone
      (FAZ). METHODS. A computerized technique for automated segmentation of the FAZ
      using images from fundus fluorescein angiography (FFA) was applied to 26 transit
      phase images obtained from patients with various grades of diabetic retinopathy.
      The area containing the FAZ zone was first extracted from the original image and
      smoothed by a Gaussian kernel (sigma = 1.5). An initializing contour was manually
      placed inside the FAZ of the smoothed image and iteratively moved by the
      segmentation program toward the FAZ boundary. Five tests with different
      initializing curves were run on each of 26 images to assess reproducibility. The
      accuracy of the program was also validated by comparing results obtained by the
      program with the FAZ boundaries manually delineated by medical retina
      specialists. Interobserver performance was then evaluated by comparing
      delineations from two of the experts. RESULTS. One-way analysis of variance
      indicated that the disparities between different tests were not statistically
      significant, signifying excellent reproducibility for the computer program. There
      was a statistically significant linear correlation between the results obtained
      by automation and manual delineations by experts. CONCLUSIONS. This automated
      segmentation program can produce highly reproducible results that are comparable
      to those made by clinical experts. It has the potential to assist in the
      detection and management of foveal ischemia and to be integrated into automated
      grading systems.

PMID- 20130280
TI  - Biometry of the cornea and anterior chamber in chinese eyes: an anterior segment
      optical coherence tomography study.
AB  - PURPOSE. To investigate the normative data of corneal and anterior segment
      biometric parameters and their associations in Chinese adults, for use in
      preoperative assessment for corneal and anterior segment surgery. METHODS. This
      cross-sectional, population-based study included 750 subjects aged > or =50
      years. The subjects underwent an ophthalmic examination including imaging with
      anterior segment optical coherence tomography (AS-OCT). Dimensions were
      subsequently measured with the Zhongshan Assessment Program (ZAP). Also measured
      was posterior corneal arc length (PCAL), a novel parameter defined as the arc
      distance between scleral spurs on the posterior border of the cornea.
      Correlations with age, sex, height, weight, body mass index (BMI), refractive
      sphere and cylinder, and intraocular pressure were also measured. RESULTS. The
      subjects' mean age was 63.3 +/- 7.9 years and 349 (46.5%) were men. Corneal
      parameters (mean +/- SD) included PCAL (12.924 +/- 0.544 mm), anterior chamber
      depth (ACD; 2.684 +/- 0.309 mm), central corneal thickness (562.39 +/- 31.85
      microm), anterior chamber curvature (7.35 +/- 0.37 mm), and posterior corneal
      curvature (6.65 +/- 0.34 mm). A moderate correlation was observed between PCAL
      and ACD (R = 0.55, P < 0.001) and a poor correlation between PCAL and age,
      height, weight, and BMI. Multivariate analysis showed a significant association
      between PCAL and ACD, ACC, PCC, and cylinder (P < 0.05). CONCLUSIONS. In this
      Chinese population, PCAL was found to correlate moderately with ACD. The data may
      be useful for corneal and anterior segment procedures such as Descemet's
      stripping automated endothelial keratoplasty (DSAEK).

PMID- 20130281
TI  - Desiccating stress promotion of Th17 differentiation by ocular surface tissues
      through a dendritic cell-mediated pathway.
AB  - PURPOSE: To explore the phenomenon that corneal and conjunctival tissues
      subjected to desiccating stress (DS) promote Th17 differentiation by stimulating
      the production of Th17-inducing cytokines through a dendritic cell (DC)-mediated
      pathway. METHODS: Experimental dry eye was created by subjecting C57BL/6 mice to
      desiccating environmental stress. Corneal and conjunctival explants from dry eye
      or control mice were cocultured with DCs for 24 hours before CD4(+) T cells were
      added for an additional 4 to 7 days. Expression of Th17-associated genes in the
      cornea, conjunctiva, DCs, and CD4(+) T cells was evaluated by real-time PCR.
      Cytokine concentrations in coculture supernatants were measured by immunobead
      assay. IL-17-producing T cells were identified by ELISPOT bioassay. RESULTS:
      Higher levels of IL-17A, TGF-beta1, TGF-beta2, IL-6, IL-23, and IL-1beta mRNA
      transcripts and TGF-beta1, IL-6, and IL-1beta protein were observed in corneal
      epithelium and conjunctiva from dry eye mice. DCs cocultured with epithelial
      explants from dry eye mice for 2 days produced higher levels of TGF-beta1, IL-6,
      IL-23, and IL-1beta mRNA transcripts and of TGF-beta1, IL-6, and IL-1beta
      protein. CD4(+) T cells cocultured with DCs and epithelial explants from dry eye
      mice expressed increased levels of IL-17A, IL-17F, IL-22, CCL-20, and retinoic
      acid receptor-related orphan receptor-gammat mRNA transcripts and increased IL
      17A protein and number of IL-17-producing T cells (Th17 cells). CONCLUSIONS:
      These findings demonstrate that DS creates an environment on the ocular surface
      that stimulates the production of Th17-inducing cytokines by corneal and
      conjunctival epithelia that promote Th17 differentiation through a dendritic cell
      mediated pathway.

PMID- 20130282
TI  - Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes.
AB  - PURPOSE. To determine which retinal layers are most affected by diabetes and
      contribute to thinning of the inner retina and to investigate the relationship
      between retinal layer thickness (LT) and diabetes duration, diabetic retinopathy
      (DR) status, age, glycosylated hemoglobin (HbA1c), and the sex of the individual,
      in patients with type 1 diabetes who have no or minimal DR. METHODS. Mean LT was
      calculated for the individual retinal layers after automated segmentation of
      spectral domain-optical coherence tomography scans of patients with diabetes and
      compared with that in control subjects. Multiple linear regression analysis was
      used to determine the relationship between LT and HbA1c, age, sex, diabetes
      duration, and DR status. RESULTS. In patients with minimal DR, the mean ganglion
      cell layer (GCL) in the pericentral area was 5.1 mum thinner (95% confidence
      interval [CI], 1.1-9.1 mum), and in the peripheral macula, the mean retinal nerve
      fiber layer (RNFL) was 3.7 mum thinner (95% CI, 1.3-6.1 mum) than in the control
      subjects. There was a significant linear correlation (R = 0.53, P < 0.01) between
      GCL thickness and diabetes duration in the pooled group of patients. Multiple
      linear regression analysis (R = 0.62, P < 0.01) showed that DR status was the
      most important explanatory variable. CONCLUSIONS. This study demonstrates GCL
      thinning in the pericentral area and corresponding loss of RNFL thickness in the
      peripheral macula in patients with type 1 diabetes and no or minimal DR compared
      with control subjects. These results support the concept that diabetes has an
      early neurodegenerative effect on the retina, which occurs even though the
      vascular component of DR is minimal.

PMID- 20130283
TI  - Suppression of laser-induced choroidal neovascularization by nontargeted siRNA.
AB  - PURPOSE. To investigate the effect of nontargeted siRNAs on vascular leakage and
      vascular endothelial growth factor (VEGF)-A expression in the development of
      choroidal neovascularization (CNV). METHODS. Nontargeted siRNAs were 21-nt
      (nucleotides) siRNA-Luc (Luciferase) or 16-nt siRNA-Luc. Targeted 21-nt siRNA
      Vegfa or phosphate-buffered saline (PBS) was used for comparison. Laser
      photocoagulation was used to induce CNV in wild-type C57BL/6J mice; 7 days later,
      vascular leakage was determined by fluorescein angiography, and CNV volumes were
      measured by confocal microscopy. Expression of VEGF-A in the retinal pigment
      epithelium (RPE)/choroid was quantified by ELISA 3 days after photocoagulation.
      RESULTS. Pathologically significant leakage developed in most of the 16nt-siRNA
      Luc- or PBS-injected mice but in significantly fewer 21nt-siRNA-Luc- and 21nt
      siRNA-Vegfa-injected mice (P = 0.0004, P = 0.0001, respectively). CNV volume in
      21-nt siRNA-Luc- and 21nt-siRNA-Vegfa-injected eyes was significantly lower than
      in PBS-injected eyes (P = 0.0124, P = 0.0040, respectively). CNV volume was not
      suppressed by 16-nt siRNA-Luc injection (P = 0.7700). The mean VEGF protein level
      decreased significantly in the 21nt-siRNA-Luc- and 21nt-siRNA-Vegfa-injected eyes
      compared with PBS-injected eyes 3 days after laser photocoagulation (P = 0.0011,
      P = 0.0063, respectively). The 16nt-siRNA-Luc-injected eyes did not show VEGF-A
      suppression 3 days after laser photocoagulation (P = 0.3177). Between 21-nt siRNA
      Luc- and 21nt-siRNA-Vegfa-injected eyes, there were no significant differences in
      CNV volume, the VEGF-A level, or pathologic leakage detected by fluorescein.
      CONCLUSIONS. These data suggest that nontarget 21nt-siRNA can suppress laser
      induced choroidal neovascularization anatomically and functionally through VEGF
      suppression.

PMID- 20130284
TI  - Neural compensation for long-term asymmetric optical blur to improve visual
      performance in keratoconic eyes.
AB  - Purpose. To investigate whether long-term visual experience with irregular
      optical blur compensates for the impact of higher-order aberration on visual
      performance in keratoconic (KC) eyes. Methods. The aberrations and high (100%)-
      and low (20%)-contrast tumbling E visual acuity (VA) were measured in four
      moderate KC eyes in which the subjects were wearing their own prescribed soft
      toric contact lenses over a 6-mm pupil. VA was measured in three emmetropic
      normal eyes for comparison with each of the four KC eyes. An adaptive optics
      system was used to correct the aberration of the normal eye and to induce the
      aberration of the KC eye simultaneously during vision testing. The magnitude of
      neural compensation was defined as improvement in VA in each KC eye compared with
      the normal eyes with KC aberrations. Results. Mean total and higher-order root
      mean square errors in the KC eyes with contact lenses were 2.72 +/- 0.83 mum and
      1.36 +/- 0.29 mum, respectively, for a 6-mm pupil. Residual RMS wavefront error
      in induction of KC aberrations on normal eyes was approximately 0.1 mum in all
      cases. Each KC eye had statistically better high (P < 0.02)- and low (P < 0.03)
      contrast VA than the three normal eyes. Mean compensation for high-contrast VA in
      logMAR was 0.12 +/- 0.09, corresponding to an improvement of 23.8%. A similar
      result was obtained for low-contrast VA. The magnitude of compensation increased
      with the severity of KC aberrations. Conclusions. In KC eyes, the neural visual
      system compensates for long-term visual experience with an asymmetrically blurred
      retinal image, resulting in improved visual performance.

PMID- 20130285
TI  - Regulation of retinal progenitor cell differentiation by bone morphogenetic
      protein 4 is mediated by the smad/id cascade.
AB  - PURPOSE. Bone morphogenetic proteins (BMPs) are secreted signaling molecules that
      are implicated in the control of multiple events during mouse eye development.
      However, little is known about the mechanisms by which BMP signaling regulates
      these retinal developmental processes. METHODS. Real-time PCR, Western blot, and
      immunohistochemistry were used to investigate the expression of components of BMP
      signaling in the mouse retina. Retinal progenitor cells (RPCs) were used to study
      the effects of BMP4 on retinal cell differentiation and regulation of Id protein
      expression. RESULTS. Results showed that BMP2, -4, and -7; BMP receptor (BMPRIb)
      mRNAs; and proteins and downstream signaling molecule Smad1/5/8 proteins were all
      highly expressed in the mouse retina during the embryonic (E13.5-E18.5) and early
      postnatal (P)1 stage and that the expression was downregulated in the adult. On
      stimulation with BMP4, cultured mouse RPCs differentiated into neuronal lineage
      whereas astrocyte cell differentiation was inhibited. BMP4 mainly stimulated
      production of retinal ganglion cells (RGCs). Results also revealed that BMPs and
      BMPRIb were co-localized with inhibitors of differentiation (Id) (mainly Id1 and 
      3) in RGCs in the adult mouse retina. Exposure of RPCs to BMP4 upregulated Id1-3
      expression levels, mediated through the phosphorylation of Smad1/5/8 proteins.
      CONCLUSIONS. These results suggest that Id genes are one of the potential targets
      of BMP signaling in the differentiation of RPCs.

PMID- 20130286
TI  - Hypotensive medication, statins, and the risk of glaucoma.
AB  - PURPOSE. To examine whether treatment with oral blood-pressure-lowering
      medication or statins influences the risk of glaucoma. METHODS. This study was a
      case-control investigation, nested within a computerized primary care database of
      177 general practices across the United Kingdom; 8778 cases diagnosed and/or
      treated for glaucoma between 2000 and 2007, and 8778 glaucoma-free controls
      matched for age, sex, and practice. Odds ratios for treatment with oral
      antihypertensives (including selective beta(1) and nonselective beta-blockers)
      and statins in the 5 years before diagnosis were calculated by logistic
      regression, adjusted for a marker of socioeconomic position and number of drug
      types prescribed (as a measure of health service usage). RESULTS. Prevalence of
      oral beta-blocker use in the 5 years before diagnosis was lower in the cases
      (22.5%) than in the controls (23.6%), adjusted odds ratio (OR) 0.87 (95%
      confidence interval [CI], 0.80-0.94). This effect was presence with treatment
      with beta(1)-selective medications (OR, 0.81; 95% CI, 0.74-0.88) but not with
      nonselective medications (OR, 1.08; 95% CI, 0.94-1.24). The prevalence of
      thiazide use was higher among the glaucoma cases than among the controls (OR,
      1.13; 95% CI, 1.04-1.23). Neither statins nor other antihypertensive treatments
      were associated with the risk of glaucoma. CONCLUSIONS. Oral beta(1) beta
      blockers may protect against development of glaucoma. The current consensus on
      the relative importance of beta(2) receptor blockade in treating glaucoma may
      have to be reviewed. Changes in prescribing oral beta-blockers for cardiovascular
      disorders may affect the number of those who eventually have glaucoma. There is
      no evidence to suggest that statins have a preventive role in glaucoma.

PMID- 20130287
TI  - Professor Giorgio Pardi and his legacy.

PMID- 20130288
TI  - Review: Lamin A/C, caspase-6, and chromatin configuration during meiosis
      resumption in the mouse oocyte.
AB  - After in vitro maturation (IVM), isolation of the healthiest oocytes is essential
      for successful in vitro fertilization. As germinal vesicle (GV) oocytes resume
      meiosis through healthy or apoptotic pathways without discernable morphological
      criteria, we checked for an apoptotic element acting at the nucleus level. We
      hypothesized that caspase-6 with its corresponding substrate, lamin A/C, could be
      a potential target candidate, because caspase-6 is the only functional caspase
      for lamin A/C. We used immunohistochemistry methods, Western blots, and a
      specific caspase-6 inhibitor to determine the presence of lamin A/C and caspase-6
      during oogenesis and in isolated oocytes. Our results demonstrated that these
      proteins were always present and that their distributions were related to oocyte
      maturity, determined by chromatin configuration and oocyte diameter. Caspase-6
      inhibition slowed meiosis resumption suggesting the involvement of caspase-6 in
      the oocyte apoptotic pathway. Lamin A/C and caspase-6 could be valuable tools in
      the knowledge of oocyte in vitro destiny.

PMID- 20130289
TI  - Answers to questions that have troubled me for years.

PMID- 20130290
TI  - How to choose your neurosurgeon.

PMID- 20130291
TI  - Neurolupus.
AB  - Systemic lupus erythematosus (SLE) is not an uncommon condition. Most
      neurologists are well aware that it can cause a wide range of neurological
      complications, and SLE almost invariably appears on 'differential diagnosis'
      lists in cases of clinical uncertainty. However, the precise nature of the
      manifestations of SLE in the central and peripheral nervous systems is perhaps
      less widely understood, and misperceptions about phenomenology and treatment are
      common. Here we survey some of the main primary neurological complications of SLE
      -'neurolupus'--while acknowledging that secondary problems, either iatrogenic or
      relating to other consequences of SLE (eg, hypertensive CNS disease, for example,
      secondary to renal lupus) are neither less serious nor less treatable.

PMID- 20130292
TI  - Deep brain stimulation for movement disorders.
AB  - Deep brain stimulation is now considered a routine treatment option for selected
      patients with advanced Parkinson's disease, primary segmental and generalised
      dystonia, and essential tremor. The neurosurgeon is responsible for the accurate
      and safe placement of the electrodes and the neurologist for the careful
      selection of patients and titration of medication against the effects of
      stimulation. A multidisciplinary team approach involving specialist nurses,
      neuropsychologists and neurophysiologists is required for a successful outcome.
      In this article we will summarise the key points in patient selection, provide an
      overview of the surgical technique, and discuss the beneficial and adverse
      outcomes that can occur.

PMID- 20130293
TI  - Drusen and the misleading optic disc.
AB  - Optic disc drusen are acellular calcified deposits occurring in small optic
      discs. They have a prevalence of up to approximately 2% and are bilateral in 75%
      of cases. Their size and fundosc pic visibility increase with age, and they are
      commonly responsible for the misdiagnosis of papilloedema by the unwary. Although
      largely asymptomatic, they can be associated with vascular problems affecting the
      optic nerve. Ocular ultrasonography is the most sensitive method for their
      detection. This article highlights their commonly encountered clinical
      presentations and the practical aspects of diagnosis and management.

PMID- 20130294
TI  - Neurological influences from Africa.

PMID- 20130295
TI  - Arsenical peripheral neuropathy.
AB  - A 49-year-old white man returned urgently to the UK after spending 3 months in
      Goa. He had a several week history of vomiting, weight loss, a widespread
      desquamating skin rash, and symptoms and signs of a progressive painful
      sensorimotor neuropathy. He had a mild normocytic anaemia and lymphopenia. Nerve
      conduction studies revealed a severe predominantly axonal large fibre
      sensorimotor neuropathy, confirmed on subsequent sural nerve biopsy. Once he had
      left Goa most of his symptoms started to rapidly settle although the neuropathic
      symptoms remained severe. Arsenic poisoning was suspected. A spot urine arsenic
      concentration was 300 microg/l, confirming the diagnosis. He was treated with
      chelation therapy. Deliberate arsenic poisoning was highly likely.

PMID- 20130296
TI  - The forearm and finger rolling tests.
AB  - A variety of clinical tests are used to detect a subtle upper motor neuron lesion
      but only a few studies have measured their sensitivity and specificity. The
      forearm rolling test and its variant, the finger rolling test, is one such. These
      tests are simple and only take 5-10 s to perform. Their sensitivity has varied in
      different studies but in general both are more likely to be abnormal in a patient
      with a focal brain lesion than abnormal power, tone and reflexes. The finger
      rolling test is more sensitive than forearm rolling. Furthermore, an abnormal
      response on testing forearm and finger rolling has a high specificity for the
      presence of a focal brain lesion.

PMID- 20130297
TI  - Meningitis associated with sphenoid sinus encephalocoele.

PMID- 20130298
TI  - Multiple intracerebral haematomas during normal intensity anticoagulation.

PMID- 20130299
TI  - Indonesia: neurology and the celebration of democracy.

PMID- 20130300
TI  - The bare essentials: coma.

PMID- 20130301
TI  - Evaluation of the health promotion model to predict physical activity in Iranian
      adolescent boys.
AB  - Promoting sustainable physical activity (PA) behavior change is challenging, and
      a number of theoretical models have been developed and applied to this problem.
      Pender's health promotion model (HPM) is a relatively new model that is based on
      Bandura's social cognitive theory but includes the additional construct of
      competing demands, which are viewed as alternative behaviors (e.g., watching
      television) that have powerful reinforcing properties. This study evaluates the
      HPM as a means to predict PA in a sample of Iranian adolescent boys. Participants
      were 515 boys from 100 junior high and high schools in Sanandaj, Iran.
      Participants' mean age was 14.33 years (SD = 1.6, range = 12-17). Participants
      completed questions assessing social cognitive variables, and structural equation
      modeling was used to fit the data to the HPM. The HPM accounted for 37% of the
      variance in PA but did not represent a good data fit (chi(2) = 913.85, df = 473,
      p < .001). There were significant pathways between PA and self-efficacy (beta =
      .25, p < .001), enjoyment (beta = .22, p < .01), and PA modeling (beta = -.13, p
      < .05). A revised model that included the indirect effects of competing demands
      explained 34% of the variance in PA and represented a good data fit (chi( 2) =
      9.12, df = 4, p = .058). In the revised model, self-efficacy, commitment to
      planning, and enjoyment were associated with PA. According to the HPM, competing
      demands influence PA. In the study sample, competing demands were not related to
      PA but were inversely associated with commitment to planning.

PMID- 20130302
TI  - An empirical test of ecodevelopmental theory in predicting HIV risk behaviors
      among Hispanic youth.
AB  - Ecodevelopmental theory is a theoretical framework used to explain the interplay
      among risk and protective processes associated with HIV risk behaviors among
      adolescents. Although ecodevelopmentally based interventions have been found to
      be efficacious in preventing HIV risk behaviors among Hispanic youth, this theory
      has not yet been directly empirically tested through a basic research study in
      this population. The purpose of this cross-sectional study was to empirically
      evaluate an ecodevelopmentally based model using structural equation modeling,
      with substance use and early sex initiation as the two outcomes of the
      ecodevelopmental chain of relationships. The sample consisted of 586 Hispanic
      youth (M age = 13.6; SD = 0.75) and their primary caregivers living in Miami,
      Florida. Adolescent, parent, and teacher reports were used. The results provided
      strong support for the theoretical model. More specifically, the parent
      adolescent acculturation gap is indirectly related both to early sex initiation
      and to adolescent substance use through family functioning, academic functioning,
      perceived peer sexual behavior, and perceived peer substance use. Additionally,
      parent's U.S. orientation is associated with adolescent substance use and
      adolescent sex initiation through social support for parents, parental stressors,
      family functioning, academic functioning, and perceived peer sexual behavior and
      substance use. These findings suggest that HIV risk behaviors may best be
      understood as associated with multiple and interrelated ecological determinants.

PMID- 20130305
TI  - Relevance of QT dispersion in haemodialysis patients.

PMID- 20130306
TI  - The diffusion gradient between the ionized calcium concentration in the dialysate
      and in the blood is the main driving force of the net calcium mass balance during
      haemodialysis.

PMID- 20130307
TI  - Orthopaedic aspects of paediatric non-accidental injury.
AB  - Non-accidental injury (NAI) in children includes orthopaedic trauma throughout
      the skeleton. Fractures with soft-tissue injuries constitute the majority of
      manifestations of physical abuse in children. Fracture and injury patterns vary
      with age and development, and NAI is intrinsically related to the mobility of the
      child. No fracture in isolation is pathognomonic of NAI, but specific abuse
      related injuries include multiple fractures, particularly at various stages of
      healing, metaphyseal corner and bucket-handle fractures and fractures of ribs.
      Isolated or multiple rib fractures, irrespective of location, have the highest
      specificity for NAI. Other fractures with a high specificity for abuse include
      those of the scapula, lateral end of the clavicle, vertebrae and complex skull
      fractures. Injuries caused by NAI constitute a relatively small proportion of
      childhood fractures. They may be associated with significant physical and
      psychological morbidity, with wide- ranging effects from deviations in normal
      developmental progression to death. Orthopaedic surgeons must systematically
      assess, recognise and act on the indicators for NAI in conjunction with the
      paediatric multidisciplinary team.

PMID- 20130308
TI  - Metal-backed acetabular components with conventional polyethylene: a review of
      9113 primary components with a follow-up of 20 years.
AB  - The Norwegian Arthroplasty Register has shown that several designs of uncemented
      femoral stems give good or excellent survivorship. The overall findings for
      uncemented total hip replacement however, have been disappointing because of poor
      results with the use of metal-backed acetabular components. In this study, we
      exclusively investigated the medium-to long-term performance of primary
      uncemented metal-backed acetabular components. A total of 9113 primary uncemented
      acetabular components were implanted in 7937 patients between 1987 and 2007.
      These were included in a prospective, population-based observational study. All
      the implants were modular and metal-backed with ultra-high-molecular-weight
      polyethylene liners. The femoral heads were made of stainless steel, cobalt
      chrome (CoCr) alloy or alumina ceramic. In all, seven different designs of
      acetabular component were evaluated by the Kaplan-Meier survivorship method and
      Cox regression analysis. Most acetabular components performed well up to seven
      years. When the endpoint was revision of the acetabular component because of
      aseptic loosening, the survival ranged between 87% and 100% at ten years.
      However, when the endpoint was revision for any reason, the survival estimates
      were 81% to 92% for the same implants at ten years. Aseptic loosening, wear,
      osteolysis and dislocation were the main reasons for the relatively poor overall
      performance of the acetabular components. Prostheses with alumina heads performed
      slightly better than those with stainless steel or CoCr alloy in subgroups.
      Whereas most acetabular components performed well at seven years, the
      survivorship declined with longer follow-up. Fixation was generally good. None of
      the metal-backed uncemented acetabular components with ultra-high-molecular
      weight polyethylene liners in our study had satisfactory long-term results
      because of high rates of wear, osteolysis, aseptic loosening and dislocation.

PMID- 20130309
TI  - The Durom large diameter head acetabular component: early results with a large
      diameter metal-on-metal bearing.
AB  - Implantation of a large-diameter femoral head prosthesis with a metal-on-metal
      bearing surface reduces the risk of dislocation, increases the range of movement,
      minimises the risk of impingement and, in theory, results in little wear. Between
      February 2004 and March 2007 we implanted 100 consecutive total hip replacements
      with a metal-on-metal bearing and a large femoral head into 92 patients. There
      were 51 men and 41 women with a mean age of 50 years (18 to 70) at the time of
      surgery. Outcome was assessed using the Western Ontario McMaster University
      osteoarthritis index and the Harris hip score as well as the Devane activity
      score. These all improved significantly (p < 0.0001). At the last follow-up there
      were no cases of dislocation, no impingement, a good range of movement and no
      osteolysis, but seven revisions, two for infection and five for aseptic
      loosening. The probability of groin pain increased if the other acetabular
      component inclination exceeded 50 degrees (p = 0.0007). At 4.8 years of follow
      up, the projected survival of the Durom acetabular component, with revision for
      any reason, was 92.4% (sd 2.8) (95% confidence interval 89.6 to 95.2). The design
      of the component made it difficult both to orientate and seat, which when
      combined with a poor porous coating, produced unpredictable fixation and a low
      survival at five years.

PMID- 20130310
TI  - Genetic influences in the aetiology of femoroacetabular impingement: a sibling
      study.
AB  - Femoroacetabular impingement causes pain in the hip in young adults and may
      predispose to the development of osteoarthritis. Genetic factors are important in
      the aetiology of osteoarthritis of the hip and may have a role in that of
      femoroacetabular impingement. We compared 96 siblings of 64 patients treated for
      primary impingement with a spouse control group of 77 individuals. All the
      subjects were screened clinically and radiologically using a standardised
      protocol for the presence of cam and pincer deformities and osteoarthritis. The
      siblings of those patients with a cam deformity had a relative risk of 2.8 of
      having the same deformity (66 of 160 siblings hips versus 23 of 154 control hips,
      p < 0.00001). The siblings of those patients with a pincer deformity had a
      relative risk of 2.0 of having the same deformity (43 of 116 sibling hips versus
      29 of 154 control hips, p = 0.001). Bilateral deformity occurred more often in
      the siblings (42 of 96 siblings versus 13 of 77 control subjects, relative risk
      2.6, p = 0.0002). The prevalence of clinical features in those hips with abnormal
      morphology was also greater in the sibling group compared with the control group
      (41 of 109 sibling hips versus 7 of 46 control hips, relative risk 2.5, p =
      0.007). In 11 sibling hips there was grade-2 osteoarthritis according to Kellgren
      and Lawrence versus none in the control group (p = 0.002). Genetic influences are
      important in the aetiology of primary femoroacetabular impingement. This risk
      appears to be manifested through not only abnormal joint morphology, but also
      through other factors which may modulate progression of the disease.

PMID- 20130311
TI  - Prognostic factors and long-term outcomes following a modified Thompson's
      quadricepsplasty for severely stiff knees.
AB  - Between 1987 and 2006 we performed a modified Thompson's quadricepsplasty on 40
      fracture-related stiff knees and followed the patients for a mean of 7.9 years (2
      to 11.1). The factors affecting the final gain of movement were investigated. A
      total of 15 knees required lengthening of the rectus femoris. The mean flexion
      gain was 70.2 degrees (42.3 degrees to 112.5 degrees ). According to Judet's
      criteria, the results were excellent in 30 knees, good in seven, and fair in
      three. The range of movement which was achieved intra-operatively was related to
      the gain of knee flexion on univariate analysis. Five patients had complications:
      deep infection in one, recurrent patellar dislocation in one, and rupture of the
      extensor mechanism in three. This modified technique gives satisfactory results.
      Achieving maximum knee flexion intra-operatively seems to be the most important
      factor in enhancing the outcome in patients with stiffness of the knee following
      fracture.

PMID- 20130312
TI  - Posteromedial meniscocapsular injury associated with rupture of the anterior
      cruciate ligament: a previously unrecognised association.
AB  - While injury to the posterolateral corner is accepted as a relatively common
      occurrence associated with rupture of the anterior cruciate ligament,
      posteromedial meniscocapsular injury has not previously been recognised as such.
      In a prospective assessment of 183 consecutive reconstructions of the anterior
      cruciate ligament this injury was observed in 17 cases, giving it an incidence of
      9.3%. Clinically, it was associated with a mild anteromedial rotatory subluxation
      and it is important not to confuse this with posterolateral rotatory subluxation.
      In no case was this injury identified by MRI. The possible long-term clinical
      relevance is discussed.

PMID- 20130313
TI  - Free vascularised iliac bone graft for recalcitrant avascular nonunion of the
      scaphoid.
AB  - We report the use of a free vascularised iliac bone graft in the treatment of 21
      patients (19 men and 2 women) with an avascular nonunion of the scaphoid in which
      conventional bone grafting had previously failed. The mean age of the patients
      was 32 years (23 to 46) and the dominant wrist was affected in 14. The mean
      interval from fracture to the vascularised bone grafting was 39 months (9 to 62).
      Pre-operative MRI showed no contrast enhancement in the proximal fragment in any
      patient. Fracture union was assessed radiologically or with CT scans if the
      radiological appearances were inconclusive. At a mean follow-up of 5.6 years (2
      to 11) union was obtained in 16 patients. The remaining five patients with a
      persistent nonunion continued to experience pain, reduced grip strength and
      limited range of wrist movement. In the successfully treated patients the grip
      strength and range of movement did not recover to match the uninjured side.
      Prevention of progressive carpal collapse, the absence of donor site morbidity,
      good subjective results and pain relief, justifies this procedure in the
      treatment of recalcitrant nonunion of the scaphoid.

PMID- 20130314
TI  - Flexor carpi ulnaris tendon transfer to the split brachioradialis tendon to
      restore supination in paralytic forearms.
AB  - Inability to actively supinate the forearm makes common activities of daily
      living and certain vocational activities awkward or impossible to perform. A
      total of 11 patients with deficient supination of the arm underwent transfer of
      the tendon of flexor carpi ulnaris to the split tendon of brachioradialis with
      its bony insertion into the radial styloid left intact. Active supination beyond
      neutral rotation was a mean of 37.2 degrees (25 degrees to 49.5 degrees ) at a
      minimum follow-up of three years, representing a significant improvement (95%
      confidence interval 25 to 50, p < 0.001). Functional evaluation of the hand after
      this transfer showed excellent and good results in ten patients and fair in one.
      The split tendon of brachioradialis as an insertion for transfer of the flexor
      carpi ulnaris appears to provide adequate supination of the forearm without
      altering the available pronation and avoids the domination of wrist extension
      sometimes associated with transfers of the flexor carpi ulnaris to the radial
      extensors of the wrist.

PMID- 20130315
TI  - Migration of the humeral component of the Souter-Strathclyde elbow prosthesis: a
      long-term RSA study.
AB  - Mechanical loosening which begins with early-onset migration of the prosthesis is
      the major reason for failure of the Souter-Strathclyde elbow replacement. In a
      prospective study of 18 Souter-Strathclyde replacements we evaluated the patterns
      of migration using roentgen stereophotogrammetric analysis. We had previously
      reported the short-term results after a follow-up of two years which we have now
      extended to a mean follow-up of 8.2 years (1 to 11.3). Migration was assessed
      along the co-ordinal axes and overall micromovement was expressed as the maximum
      total point movement. The alignment of the prosthesis and the presence of
      radiolucent lines were examined on conventional standardised radiographs. All the
      humeral components showed increased and variable patterns of migration at the
      extended follow-up and four humeral components were revised. The maximum total
      point movement at two years in the revised prostheses was 1.8 mm (sd 1.0) and in
      the non-revised 0.7 mm (sd 0.5, p = 0.01). Most humeral components migrated into
      external rotation resulting in an anterior and varus tilt. The ulnar components
      remained stable.

PMID- 20130316
TI  - Coccygectomy: an effective treatment option for chronic coccydynia: retrospective
      results in 41 consecutive patients.
AB  - Between 1993 and 2008, 41 patients underwent total coccygectomy for coccydynia
      which had failed to respond to six months of conservative management. Of these,
      40 patients were available for clinical review and 39 completed a questionnaire
      giving their evaluation of the effect of the operation. Excellent or good results
      were obtained in 33 of the 41 patients, comprising 18 of the 21 patients with
      coccydynia due to trauma, five of the eight patients with symptoms following
      childbirth and ten of 12 idiopathic onset. In eight patients the results were
      moderate or poor, although none described worse pain after the operation. The
      only post-operative complication was superficial wound infection which occurred
      in five patients and which settled fully with antibiotic treatment. One patient
      required re-operation for excision of the distal cornua of the sacrum. Total
      coccygectomy offered satisfactory relief of pain in the majority of patients
      regardless of the cause of their symptoms.

PMID- 20130317
TI  - Neglected traumatic dislocation of the subaxial cervical spine.
AB  - The optimal method for the management of neglected traumatic bifacetal
      dislocation of the subaxial cervical spine has not been established. We treated
      four patients in whom the mean delay between injury and presentation was four
      months (1 to 5). There were two dislocations at the C5-6 level and one each at C4
      5 and C3-4. The mean age of the patients was 48.2 years (27 to 60). Each patient
      presented with neck pain and restricted movement of the cervical spine. Three of
      the four had a myelopathy. We carried out a two-stage procedure under the same
      anaesthetic. First, a posterior soft-tissue release and partial facetectomy were
      undertaken. This allowed partial reduction of the dislocation which was then
      supplemented by interspinous wiring and corticocancellous graft. Next, through an
      anterior approach, discectomy, tricortical bone grafting and anterior cervical
      plating were carried out. All the patients achieved a nearly anatomical reduction
      and sagittal alignment. The mean follow-up was 2.6 years (1 to 4). The myelopathy
      settled completely in the three patients who had a pre-operative neurological
      deficit. There was no graft dislodgement or graft-related problems. Bony fusion
      occurred in all patients and a satisfactory reduction was maintained. The
      posteroanterior procedure for neglected traumatic bifacetal dislocation of the
      subaxial cervical spine is a good method of achieving sagittal alignment with
      less risk of iatrogenic neurological injury, a reduced operating time, decreased
      blood loss, and a shorter hospital stay compared with other procedures.

PMID- 20130318
TI  - Fractures of the acetabulum in patients aged 60 years and older: an
      epidemiological and radiological study.
AB  - Using a prospective database of 1309 displaced acetabular fractures gathered
      between 1980 and 2007, we calculated the annual mean age and annual incidence of
      elderly patients > 60 years of age presenting with these injuries. We compared
      the clinical details and patterns of fracture between patients > 60 years of age
      (study group) with those < 60 years (control group). We performed a detailed
      evaluation of the radiographs of the older group to determine the incidence of
      radiological characteristics which have been previously described as being
      associated with a poor patient outcome. In all, 235 patients were > 60 years of
      age and the remaining 1074 were < 60 years. The incidence of elderly patients
      with acetabular fractures increased by 2.4-fold between the first half of the
      study period and the second half (10% (62) vs 24% (174), p < 0.001). Fractures
      characterised by displacement of the anterior column were significantly more
      common in the elderly compared with the younger patients (64% (150) vs 43% (462),
      respectively, p < 0.001). Common radiological features of the fractures in the
      study group included a separate quadrilateral-plate component (50.8% (58)) and
      roof impaction (40% (46)) in the anterior fractures, and comminution (44% (30))
      and marginal impaction (38% (26)) in posterior-wall fractures. The proportion of
      elderly patients presenting with acetabular fractures increased during the 27
      year period. The older patients had a different distribution of fracture pattern
      than the younger patients, and often had radiological features which have been
      shown in other studies to be predictive of a poor outcome.

PMID- 20130319
TI  - Age-specific incidence of first and second fractures of the hip.
AB  - We determined the age-specific incidence of a second fracture of the hip and
      compared it with that of a primary fracture in a study population drawn from 6331
      patients admitted to Nottingham University Hospital with a primary fracture of
      the hip over a period of 8.5 years. The incidence of a second fracture was
      determined using survival analysis. The mean age-specific incidence rates of
      primary hip fracture were calculated using census data. The overall incidence of
      a second fracture was 2.7% at one year and 7.8% at 8.5 years. That of a primary
      fracture was 50 per 100 000 in women aged 55 to 64 years rising to 3760 in those
      aged 84 years and over. The incidence of a second fracture in women aged 55 to 64
      years was 2344 per 100 000. Patients of this age had a relative risk of 45 (95%
      confidence interval 13 to 155) for further fracture when compared with the
      population at risk of a first fracture. The incidence of a second fracture in
      women aged > 84 years was 2451 per 100 000 (relative risk 0.7, 95% confidence
      interval 0.5 to 0.9). A similar trend was seen in men. Patients sustaining a
      primary fracture of the hip between the ages of 55 and 64 years have a much
      greater risk of further fracture than the normal population, whereas those over
      84 years have a similar risk. These findings have important implications for the
      provision of fracture prevention services in primary and secondary care.

PMID- 20130320
TI  - Elastofibroma dorsi: management, outcome and review of the literature.
AB  - Elastofibroma dorsi is an uncommon, benign, slow-growing soft-tissue tumour of
      uncertain aetiology. It classically presents as an ill-defined mass at the
      inferior pole of the scapula with symptoms which include swelling, discomfort,
      snapping, stiffness and occasionally pain. We report the symptoms, function and
      outcome after treatment of 21 elastofibromas in 15 patients. All were diagnosed
      by MRI and early in the series four also underwent CT-guided biopsy to confirm
      the diagnosis. In all, 18 tumours were excised and three were observed. After
      excision, the mean visual analogue score for pain decreased from 4.6 (0 to 10)
      pre-operatively to 2.4 (0 to 8) post-operatively (p = 0.04). The mean shoulder
      function, at a mean follow-up of 4.2 years (3 months to 16 years), was 78.1% (30
      to 100) using the Stanmore percentage of normal shoulder assessment scoring
      system. The mean range of forward flexion improved from 135 degrees (70 degrees
      to 180 degrees ) to 166 degrees (100 degrees to 180 degrees ) after excision (p =
      0.005). In four patients a post-operative haematoma formed; one required
      evacuation. Three patients developed a post-operative seroma requiring needle
      aspiration and one developed a superficial infection which was treated with
      antibiotics. Our findings support previous reports suggesting that a pre
      operative tissue diagnosis is not necessary in most cases since the lesion can be
      confidently diagnosed by MRI, when interpreted in the light of appropriate
      clinical findings. Surgical excision in symptomatic patients, is helpful. It has
      been suggested that elastofibroma is caused by a local tissue reaction and is not
      a true neoplastic process. A strong association has been noted between
      elastofibroma and repetitive use of the shoulder, which is supported by our
      findings.

PMID- 20130321
TI  - Management of combined nonunion and limb-length discrepancy after vascularised
      fibular grafting.
AB  - We describe the management of nonunion combined with limb-length discrepancy
      following vascularised fibular grafting for the reconstruction of long-bone
      defects in the lower limb after resection of a tumour in skeletally immature
      patients. We operated on nine patients with a mean age of 13.1 years (10.5 to
      14.5) who presented with a mean limb-length discrepancy of 7 cm (4 to 9) and
      nonunion at one end of a vascularised fibular graft, which had been performed
      previously, to reconstruct a bone defect after resection of an osteosarcoma.
      Reconstruction was carried out using a ring fixator secured with correction by
      half pins of any malalignment, compression of the site of nonunion and
      lengthening through a metaphyseal parafocal osteotomy without bone grafting. The
      expected limb-length discrepancy at maturity was calculated using the arithmetic
      method. Solid union and the intended leg length were achieved in all the
      patients. Excessive scarring and the distorted anatomy from previous surgery in
      these patients required other procedures to be performed with minimal exposures
      and dissection in order to avoid further compromise to the vascularity of the
      graft or damage to neurovascular structures. The methods which we chose were
      simple and effective in addressing these complex problems.

PMID- 20130322
TI  - Correcting genu varum and genu valgum in children by guided growth: temporary
      hemiepiphysiodesis using tension band plates.
AB  - A total of 25 children (37 legs and 51 segments) with coronal plane deformities
      around the knee were treated with the extraperiosteal application of a flexible
      two-hole plate and screws. The mean age was 11.6 years (5.5 to 14.9), the median
      angle of deformity treated was 8.3 degrees and mean time for correction was 16.1
      months (7 to 37.3). There was a mean rate of correction of 0.7 degrees per month
      in the femur (0.3 degrees to 1.5 degrees ), 0.5 degrees per month in the tibia
      (0.1 degrees to 0.9 degrees ) and 1.2 degrees per month (0.1 degrees to 2.2
      degrees ) if femur and tibia were treated concurrently. Correction was faster if
      the child was under 10 years of age (p = 0.05). The patients were reviewed
      between six and 32 months after plate removal. One child had a rebound deformity
      but no permanent physeal tethers were encountered. The guided growth technique,
      as performed using a flexible titanium plate, is simple and safe for treating
      periarticular deformities of the leg.

PMID- 20130323
TI  - Transfer of the tendon of tibialis anterior in relapsed congenital clubfoot: long
      term results in 38 feet.
AB  - A total of 38 relapsed congenital clubfeet (16 stiff, 22 partially correctable)
      underwent revision of soft-tissue surgery, with or without a bony procedure, and
      transfer of the tendon of tibialis anterior at a mean age of 4.8 years (2.0 to
      10.1). The tendon was transferred to the third cuneiform in five cases, to the
      base of the third metatarsal in ten and to the base of the fourth in 23. The
      patients were reviewed at a mean follow-up of 24.8 years (10.8 to 35.6). A total
      of 11 feet were regarded as failures (one a tendon failure, five with a subtalar
      fusion due to over-correction, and five with a triple arthrodesis due to under
      correction or relapse). In the remaining feet the clinical outcome was excellent
      or good in 20 and fair or poor in seven. The mean Laaveg-Ponseti score was 81.6
      of 100 points (52 to 92). Stiffness was mild in four feet and moderate or severe
      in 23. Comparison between the post-operative and follow-up radiographs showed
      statistically significant variations of the talo-first metatarsal angle towards
      abduction. Variations of the talocalcaneal angles and of the overlap ratio were
      not significant. Extensive surgery for relapsed clubfoot has a high rate of poor
      long-term results. The addition of transfer of the tendon of tibialis anterior
      can restore balance and may provide some improvement of forefoot adduction.
      However, it has a considerable complication rate, including failure of transfer,
      over-correction, and weakening of dorsiflexion. The procedure should be reserved
      for those limited cases in which muscle imbalance is a causative or contributing
      factor.

PMID- 20130324
TI  - A case of necrotising fasciitis caused by Pseudomonas aeruginosa.
AB  - Necrotising fasciitis is a rare but severe infection of soft-tissue associated
      with rapid progression, systemic toxicity and high mortality. Monomicrobial
      necrotising fasciitis caused by Pseudomonas aeruginosa is exceptionally uncommon
      with only 12 cases reported in the literature. We describe a fatal case with an
      atypical presentation in a patient following spinal decompression for a
      metastasis from prostate cancer.

PMID- 20130325
TI  - Severe rotational deformity, quadriparesis and respiratory embarrassment due to
      osteomyelitis at the occipito-atlantoaxial junction.
AB  - We present the case of an 83-year-old man who developed quadriparesis and
      respiratory embarrassment following osteomyelitis at the occipito-atlantoaxial
      junction. He had developed an abscess at this site after an earlier urinary
      infection with methicillin-resistant staphylococcus aureus. Stabilisation of the
      neck and antibiotic therapy led to an almost complete neurological recovery
      without recourse to anterior surgery.

PMID- 20130326
TI  - Bilateral hip replacement in three patients with lysosomal storage disease:
      Mucopolysaccharidosis type IV and Mucolipidosis type III.
AB  - The management of joint replacement in lysosomal storage diseases has not been
      well reported. We present three patients with progressive degenerative changes of
      the hips who required bilateral total hip replacement in early childhood. The
      stature of the patients make it essential to have access to appropriately scaled
      prostheses. Consideration has to be given to associated disorders of the skeleton
      which must be carefully screened to ensure safety in providing appropriate
      anaesthesia as well as ensuring that there is no cardiac abnormality. In one
      patient, a periprosthetic fracture was sustained in one hip in the early post
      operative course requiring internal fixation. The patient made a full recovery
      and all six hips were clinically and radiologically satisfactory at mid-term
      review.

PMID- 20130327
TI  - Ulnar dimelia without duplicated arterial anatomy.
AB  - In this case report a four-year-old girl with ulnar dimelia is described. She had
      six digits without mirror symmetry in her right hand. The first pre-axial digit
      was excised and true pollicisation performed for the second pre-axial digit. The
      arterial anatomy was abnormal but there was not symmetrical development of the
      arterial tree.

PMID- 20130328
TI  - Lack of a central role for osteoprogenitor cells from the femoral canal in
      heterotopic ossification of the hip: an experimental study in a rat model.
AB  - We have developed an animal model to examine the formation of heterotopic
      ossification using standardised muscular damage and implantation of a beta
      tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim
      was to investigate how cells originating from drilled femoral canals and damaged
      muscles influence the formation of heterotopic bone. The femoral canal was either
      drilled or left untouched and a tricalcium phosphate block, immersed either in
      saline or a rhBMP-2 solution, was implanted. These implants were removed at three
      and 21 days after the operation and examined histologically,
      histomorphometrically and immunohistochemically. Bone formation was seen in all
      implants in rhBMP-2-immersed, whereas in those immersed in saline the process was
      minimal, irrespective of drilling of the femoral canals. Bone mineralisation was
      somewhat greater in the absence of drilling with a mean mineralised volume to
      mean total volume of 18.2% (sd 4.5) versus 12.7% (sd 2.9, p < 0.019),
      respectively. Our findings suggest that osteoinductive signalling is an early
      event in the formation of ectopic bone. If applicable to man the results indicate
      that careful tissue handling is more important than the prevention of the
      dissemination of bone cells in order to avoid heterotopic ossification.

PMID- 20130329
TI  - The prophylactic effects of platelet-leucocyte gel in osteomyelitis: an
      experimental study in a rabbit model.
AB  - Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto
      been used primarily to treat chronic ulcers and to promote soft-tissue and bone
      regeneration in a wide range of medical fields. In this study, the antimicrobial
      efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a
      rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal
      after inoculation with Staph. aureus. The prophylactic efficacy of PLG was
      evaluated by microbiological, radiological and histological examination. Animal
      groups included a treatment group that received systemic cefazolin and a control
      group that received no treatment. Treatment with PLG or cefazolin significantly
      reduced radiological and histological severity scores compared to the control
      group. This result was confirmed by a significant reduction in the infection rate
      and the number of viable bacteria. Although not comparable to cefazolin, PLG
      exhibited antimicrobial efficacy in vivo and therefore represents a novel
      strategy to prevent bone infection in humans.

PMID- 20130330
TI  - Is the human acetabulofemoral joint spherical?
AB  - The human acetabulofemoral joint is commonly modelled as a pure ball-and-socket
      joint, but there has been no quantitative assessment of this assumption in the
      literature. Our aim was to test the limits and validity of this hypothesis. We
      performed experiments on four adult cadavers. Cortical pins, each equipped with a
      marker cluster, were implanted in the pelvis and the femur. Movements were
      recorded using stereophotogrammetry while an operator rotated the cadaver's
      acetabulofemoral joint, exploiting the widest possible range of movement. The
      functional consistency of the acetabulofemoral joint as a pure spherical joint
      was assessed by comparing the magnitude of the translations of the hip joint
      centre as obtained on cadavers, with the centre of rotation of two metal segments
      linked through a perfectly spherical hinge. The results showed that the radii of
      the spheres containing 95% of the positions of the estimated centres of rotation
      were separated by less than 1 mm for both the acetabulofemoral joint and the
      mechanical spherical hinge. Therefore, the acetabulofemoral joint can be modelled
      as a spherical joint within the considered range of movement (flexion/extension
      20 degrees to 70 degrees ; abduction/adduction 0 degrees to 45 degrees ;
      internal/external rotation 0 degrees to 30 degrees ).

PMID- 20130331
TI  - The use of three types of suture and stainless steel wire tension banding for the
      fixation of simulated olecranon fractures: a comparison study in cadaver elbows.
AB  - Using an osteotomy of the olecranon as a model of a transverse fracture in 22
      cadaver elbows we determined the ability of three different types of suture and
      stainless steel wire to maintain reduction when using a tension-band technique to
      stabilise the bone. Physiological cyclical loading simulating passive elbow
      movement (15 N) and using the arms to push up from a chair (450 N) were applied
      using an Instron materials testing machine whilst monitoring the osteotomy site
      with a video extensometer. Each osteotomy was repaired by one of four materials,
      namely, Stainless Steel Wire (7), No 2 Ethibond (3), No 5 Ethibond (5), or No 2
      FiberWire (7). There were no failures (movement of > 2 mm) with stainless steel
      wire or FiberWire and no significant difference in the movements measured across
      the site of the osteotomy (p = 0.99). The No. 2 Ethibond failed at 450 N and two
      of the five of No. 5 Ethibond sutures had a separation of > 2 mm at 450 N.
      FiberWire as the tension band in this model held the reduction as effectively as
      stainless steel wire and may reduce the incidence of discomfort from the
      hardware. On the basis of our findings we suggest that a clinical trial should be
      undertaken.

PMID- 20130332
TI  - The use of silk fibroin/hydroxyapatite composite co-cultured with rabbit bone
      marrow stromal cells in the healing of a segmental bone defect.
AB  - In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite
      (SF/HA) composite on the repair of a segmental bone defect. Four types of porous
      SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material
      ratios, pore sizes, porosity and additives were implanted subcutaneously into
      Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics
      more suitable for a bone substitute based on strength and resorption was selected
      as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A
      segmental bone defect was created in the rabbit radius. The animals were
      randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone
      defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They
      were killed at four, eight and 12 weeks for visual, radiological and histological
      study. The bone defects had complete union for group 1 and partial union in group
      2, 12 weeks after operation. There was no formation of new bone in group 3. We
      conclude that SF/HA-3 combined with BMSCs supports bone healing and offers
      potential as a bone-graft substitute.

PMID- 20130340
TI  - The folding of knotted proteins: insights from lattice simulations.
AB  - We carry out systematic Monte Carlo simulations of Go lattice proteins to
      investigate and compare the folding processes of two model proteins whose native
      structures differ from each other due to the presence of a trefoil knot located
      near the terminus of one of the protein chains. We show that the folding time of
      the knotted fold is larger than that of the unknotted protein and that this
      difference in folding time is particularly striking in the temperature region
      below the optimal folding temperature. Both proteins display similar folding
      transition temperatures, which is indicative of similar thermal stabilities. By
      using the folding probability reaction coordinate as an estimator of folding
      progression we have found out that the formation of the knot is mainly a late
      folding event in our shallow knot system.

PMID- 20130341
TI  - Kinetic models for autopoietic chemical systems: the role of fluctuations in a
      homeostatic regime.
AB  - Two kinetic models describing the emergence of autopoietic chemical units are
      presented and discussed: the single reagent autopoietic mechanism (SRAM) and a
      reduced version (rSRAM). The proposed schemes are inspired to the autopoietic
      vesicles studied by Zepik et al (2001 Angew. Chem., Int. Ed. Engl. 40 199-202).
      Deterministic and stochastic analyses are then performed in order to obtain
      conditions for growth, homeostasis and decay time behaviours of the overall
      amphiphiles concentration. Only the reduced SRAM is able to exhibit all the three
      regimes as experimentally observed and in order to obtain details on the time
      evolution of the aggregates' size distribution, stochastic simulations are
      carried out. What emerges from the rSRAM simulation outcomes is that random
      fluctuations can act as selection rules for the size of the autopoietic units in
      the homeostatic regime suggesting how, in a prebiotic scenario, stochastic
      fluctuations can select the more robust, in this case larger, as the fittest
      'organisms'.

PMID- 20130342
TI  - The classification of oximetry signals using Bayesian neural networks to assist
      in the detection of obstructive sleep apnoea syndrome.
AB  - In the present study, multilayer perceptron (MLP) neural networks were applied to
      help in the diagnosis of obstructive sleep apnoea syndrome (OSAS). Oxygen
      saturation (SaO(2)) recordings from nocturnal pulse oximetry were used for this
      purpose. We performed time and spectral analysis of these signals to extract 14
      features related to OSAS. The performance of two different MLP classifiers was
      compared: maximum likelihood (ML) and Bayesian (BY) MLP networks. A total of 187
      subjects suspected of suffering from OSAS took part in the study. Their SaO(2)
      signals were divided into a training set with 74 recordings and a test set with
      113 recordings. BY-MLP networks achieved the best performance on the test set
      with 85.58% accuracy (87.76% sensitivity and 82.39% specificity). These results
      were substantially better than those provided by ML-MLP networks, which were
      affected by overfitting and achieved an accuracy of 76.81% (86.42% sensitivity
      and 62.83% specificity). Our results suggest that the Bayesian framework is
      preferred to implement our MLP classifiers. The proposed BY-MLP networks could be
      used for early OSAS detection. They could contribute to overcome the difficulties
      of nocturnal polysomnography (PSG) and thus reduce the demand for these studies.

PMID- 20130343
TI  - Intra-inter visit reproducibility of short-term linear and nonlinear measurement
      of heart rate variability in tetraplegia and neurologically intact controls.
AB  - Heart rate variability (HRV) from the frequency domain and three calculations of
      entropy (En), approximate (ApEn), sample (SampEn) and Lempel-Ziv (LZEn), were
      assessed for intra- and inter-visit reproducibility from short-term recordings in
      persons with tetraplegia and neurologically intact controls. The intraclass
      correlation coefficient (ICC) was calculated for multiple comparisons to
      determine the reproducibility in both groups during a 4 h visit and across three
      visits. By ICC in both groups, ApEn, SampEn and LZEn possessed excellent intra-
      (>or=0.87) and inter-visit reproducibility (>or=0.90). In contrast, frequency
      domain measures were collectively less concise. In general on intra- and inter
      visit comparisons for both groups, high frequency (HF) measures were more
      reliable than low frequency (LF). In control subjects relative to other units of
      expression, normalized units (nu) of LF had the best intra-visit reliability
      across all comparisons. This was not the case on inter-visit comparisons where
      absolute (>or=0.74) and natural log (ln) (>or=0.66) representations of LF were
      more reliable. In the group with tetraplegia, LFln was the most reliable for
      comparisons up to or including 180 min (>or=0.60) and two visits (>or=0.63).
      Thus, calculations of En and HF HRV appear to be more reliable than LF HRV and
      less confounded by small sample sizes.

PMID- 20130344
TI  - Automatic classification of transient ischaemic and transient non-ischaemic heart
      rate related ST segment deviation episodes in ambulatory ECG records.
AB  - In ambulatory ECG records, besides transient ischaemic ST segment deviation
      episodes, there are also transient non-ischaemic heart-rate related ST segment
      deviation episodes present, which appear only due to a change in heart rate and
      thus complicate automatic detection of true ischaemic episodes. The goal of this
      work was to automatically classify these two types of episodes. The tested
      features to classify the ST segment deviation episodes were changes of heart
      rate, changes of the Mahalanobis distance of the first five Karhunen-Loeve
      transform (KLT) coefficients of the QRS complex, changes of time-domain
      morphologic parameters of the ST segment and changes of the Legendre orthonormal
      polynomial coefficients of the ST segment. We chose Legendre basis functions
      because they best fit typical shapes of the ST segment morphology, thus allowing
      direct insight into the ST segment morphology changes through the feature space.
      The classification was performed with the help of decision trees. We tested the
      classification method using all records of the Long-Term ST Database on all
      ischaemic and all non-ischaemic heart-rate related deviation episodes according
      to annotation protocol B. In order to predict the real-world performance of the
      classification we used second-order aggregate statistics, gross and average
      statistics, and the bootstrap method. We obtained the best performance when we
      combined the heart-rate features, the Mahalanobis distance and the Legendre
      orthonormal polynomial coefficient features, with average sensitivity of 98.1%
      and average specificity of 85.2%.

PMID- 20130345
TI  - An examination of mechanomyographic signal stationarity during concentric
      isokinetic, eccentric isokinetic and isometric muscle actions.
AB  - The purpose of the present study was to examine the stationarity of surface
      mechanomyographic (MMG) signals from the vastus lateralis, rectus femoris and
      vastus medialis during concentric isokinetic, eccentric isokinetic and isometric
      muscle actions of the leg extensors. Eleven healthy men (mean +/- SD age = 20.1
      +/- 1.1 years) performed submaximal to maximal concentric isokinetic, eccentric
      isokinetic and isometric muscle actions of the leg extensors, and surface MMG
      signals were detected from the vastus lateralis, rectus femoris and vastus
      medialis. All surface MMG signals were tested for stationarity with a procedure
      that examined changes in the mean value, variance, mean frequency and standard
      deviation of the power spectrum over time. The results showed that the three
      muscle action types resulted in similar levels of signal nonstationarity. Thus,
      despite the fact that the isometric muscle actions were performed at a constant
      force level and with no change in muscle length, the level of signal
      nonstationarity was similar to that for the concentric and eccentric isokinetic
      muscle actions. Future studies need to be done to identify the mechanism(s)
      causing MMG signal nonstationarity during isometric muscle actions.

PMID- 20130346
TI  - Ignition and temperature behavior of a single-wall carbon nanotube sample.
AB  - The electrical resistance of mats of single-wall carbon nanotubes (SWNTs) is
      measured as a function of mat temperature under various helium pressures, in
      vacuum and in atmospheric air. The objective of this paper is to study the
      thermal stability of SWNTs produced in a helium arc discharge in the experimental
      conditions close to natural conditions of SWNT growth in an arc, using a furnace
      instead of an arc discharge. For each tested condition, there is a temperature
      threshold at which the mat's resistance reaches its minimum. The threshold value
      depends on the helium pressure. An increase of the temperature above the
      temperature threshold leads to the destruction of SWNT bundles at a certain
      critical temperature. For instance, the critical temperature is about 1100 K in
      the case of helium background at a pressure of about 500 Torr. Based on
      experimental data on critical temperature it is suggested that SWNTs produced by
      an anodic arc discharge and collected in the web area outside the arc plasma most
      likely originate from the arc discharge peripheral region.

PMID- 20130347
TI  - Self-organized formation and self-repair of a two-dimensional nanoarray of Ge
      quantum dots epitaxially grown on ultrathin SiO2-covered Si substrates.
AB  - Two-dimensional nanoarrays of Ge quantum dots (QDs) with the ability to self
      repair were epitaxially grown by self-organization on Si substrates using an
      ultrathin SiO(2) film technique. Nanometer-sized voids were patterned on
      ultrathin SiO(2) films by transcription of the pattern of block copolymer films
      using a selective etching method and worked as nucleation sites for QD growth.
      The epitaxial QDs were elastically strain-relaxed without misfit dislocations and
      of uniform size. The epitaxial structures of Si-capped QD nanoarrays exhibited
      strong photoluminescence near 1.5 microm.

PMID- 20130348
TI  - Impact of dimerization and stretching on the transport properties of molybdenum
      atomic wires.
AB  - We study the electrical and transport properties of monatomic Mo wires with
      different structural characteristics. We consider first periodic wires with
      interatomic distances ranging between the dimerized wire to that formed by
      equidistant atoms. We find that the dimerized case has a gap in the electronic
      structure which makes it insulating, as opposed to the equidistant or near
      equidistant cases which are metallic. We also simulate two conducting one
      dimensional Mo electrodes separated by a scattering region which contains a
      number of dimers between 1 and 6. The I-V characteristics strongly depend on the
      number of dimers and vary from ohmic to tunneling, with the presence of different
      gaps. We also find that stretched chains are ferromagnetic.

PMID- 20130349
TI  - Si nanowire metal-insulator-semiconductor photodetectors as efficient light
      harvesters.
AB  - Novel ITO-Si nanowire (NW) metal-insulator-semiconductor (MIS) photodetectors
      were fabricated by using n-type Si NWs as detection units and ITO films as top
      gate electrodes. Measurements on the Si NW based device reveal a significant
      photoresponse, including photocurrent generation with an external quantum
      efficiency (EQE) of approximately 35% at a peak wavelength of 600 nm at zero
      external bias, and with an EQE of 70% at a peak wavelength of 800 nm at - 0.5 V
      bias. The NW device shows a flat and low reflectance and almost constant EQE up
      to a 60 degrees incident angle of illumination, demonstrating efficient visible
      light harvesting by the Si NW antenna.

PMID- 20130350
TI  - Hypoxic-ischemic brain injury: addressing the disconnect between pathophysiology
      and public policy.

PMID- 20130351
TI  - Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms.
AB  - Hypoxic-ischemic brain injury is a well known consequence of cardiac arrest.
      Variable injuries can occur with purely hypoxic or histotoxic insults such as
      asphyxiation and carbon monoxide poisoning. The injury may happen at the time of
      the insult, but there may also be continued damage after circulation and
      oxygenation are reestablished. The nature and extent of the damage appears to
      depend on the severity, time course and duration of the oxygen deprivation and
      lack of blood supply, as well as on the underlying mechanism. This review
      describes the pathophysiological and molecular basis of hypoxic ischemic brain
      injury, and differentiates between the mechanisms of injury by cardiac arrest,
      pure respiratory arrest, and arrest secondary to cytotoxicity (e.g. carbon
      monoxide poisoning).

PMID- 20130352
TI  - Neuroimaging of hypoxic-ischemic brain injury.
AB  - Hypoxic-ischemic brain injury (HI-BI) is a common cause of neurological morbidity
      in children and adults. Recent developments in neuroimaging techniques may permit
      in vivo identification of the structural and functional anatomy of HI-BI, and
      offer opportunities for the development of neuroimaging-guided prognosis. This
      article provides an update on the types and possible roles of currently-available
      neuroimaging techniques. The applications and limitations of these techniques to
      the study and clinical evaluation of persons with HI-BI are discussed, and the
      need of further research is highlighted.

PMID- 20130353
TI  - Neurocognitive outcomes following neonatal encephalopathy.
AB  - Neonatal encephalopathy (NE) from perinatal asphyxia (PA) has long been
      recognized as an important cause of lasting motor impairment in term newborns. NE
      has also, more recently, been implicated as an important risk factor for
      cognitive and behavioral difficulties as these children age. Newborns with mild
      NE appear to have normal neurocognitive outcomes, while those survivors with
      severe NE tend to have profound impediments. Yet, newborns with moderate NE seem
      to exhibit a wide range of cognitive outcomes - regardless of motor function -
      making prognostication in these children difficult in the newborn period. Since
      deficits are often subtle and remote from the initial injury, cognitive
      impairment is likely underdiagnosed in survivors of moderate perinatal NE.
      Therefore, it is important for ongoing formal neuropsychological evaluation, as
      well as parental and teacher education, to help aid in the cognitive and
      behavioral rehabilitation resulting from NE and perinatal hypoxic-ischemic brain
      injury.

PMID- 20130354
TI  - Neurological sequelae of hypoxic-ischemic brain injury.
AB  - Hypoxic-ischemic brain injury (HI-BI) after cardiac arrest commonly results in
      neurological injury and long term dysfunction, with outcomes ranging from coma
      and vegetative states to functional disability with various degrees of
      dependence. Increased rates of bystander CPR and cardiac defibrillation has led
      to a rapid increase in successful resuscitations. Patients who reach the hospital
      after cardiac arrest may develop various neurological deficits or clinical
      syndromes that may preclude recovery to their premorbid baseline. Consequently,
      clinicians are faced with not only predicting outcome regarding wakefulness and
      independence but also with long term therapeutic management. Several neurological
      syndromes have been reported as consequences of HI-BI. This review will describe
      some of the more common syndromes seen after HI-BI, including the various levels
      of arousal, seizures, myoclonus, movement disorders, cognitive impairments, and
      other specific neurological abnormalities.

PMID- 20130355
TI  - Cognitive sequelae of hypoxic-ischemic brain injury: a review.
AB  - Despite improvements in the pre-hospital and critical care management of persons
      with hypoxic-ischemic brain injury (HI-BI) and the conditions with which it is
      associated, acute and chronic cognitive impairments remain problems for many
      survivors of such injuries. Disorders of consciousness, attention, speed of
      processing, and memory impairments, and executive dysfunction are among the most
      prominent and common disturbances of cognition after HI-BI. Acute interventions,
      including therapeutic hypothermia, may improve global outcomes after HI-BI, but
      their specific effects on post-hypoxic cognitive impairments remain uncertain.
      Additionally, treatments for cognitive impairments after HI-BI are underdeveloped
      and are generally arrived at by analogy to the treatment of such problems arising
      from other neurological conditions, especially traumatic brain injury. In the
      service of offering a practical approach to the evaluation and care of persons
      with cognitive impairments after HI-BI, the most common types of post-hypoxic
      cognitive impairments are reviewed. Cognitive outcomes after HI-BI are discussed
      and suggestions for the nonpharmacologic and pharmacologic neurorehabilitation of
      these problems are offered.

PMID- 20130356
TI  - Hypobaric hypoxic cerebral insults: the neurological consequences of going
      higher.
AB  - As increasing numbers of people live, work, and play at high altitudes, awareness
      of the neurological consequences of hypobaric hypoxic environments becomes
      paramount. Despite volumes of studies examining the pathophysiology of altitude
      sickness, the underlying mechanisms of the spectrum of altitude related illnesses
      is still elusive. High altitude headache, acute mountain sickness, high altitude
      cerebral edema and other neurological presentations including sleep disturbances
      and seizures at high altitude are reviewed. As our knowledge advances in the
      field of altitude physiology, the clinical and research techniques developed may
      help our understanding of hypoxic brain injury in general.

PMID- 20130357
TI  - Neurological and neurobehavioral sequelae of obstructive sleep apnea.
AB  - Hypoxic-ischemic brain damage often results from a combination of cardiogenic and
      respiratory failure. Whether or not hypoxia in the absence of ischemia is
      injurious to the brain has been a topic of research. An example of hypoxia
      without ischemia is found in obstructive sleep apnea (OSA), which causes
      recurrent nocturnal oxygen desaturations. Furthermore, it is a pervasive problem
      in the general population, particularly in people with common disorders such as
      obesity or diabetes. Mounting evidence in the past decade indicates that
      cerebrovascular disease, specifically stroke, and neurobehavioral consequences,
      including excessive daytime sleepiness and cognitive deficits, are prevalent in
      people with OSA, at great costs to the individual well-being, public health, and
      the economy. Investigation of the two disease associations poses similar and
      unique challenges. Predictors of these sequelae need to be better defined. The
      apnea-hypopnea index, the most common measure of OSA, has proven to be variably
      related to stroke and cognitive impairment. The role of individual markers,
      whether they are comorbidities or differences in inherent cognitive reserve, also
      is incompletely understood. This review discusses the burgeoning literature on
      the neurological and neurobehavioral sequelae of OSA and highlights the future
      avenues of research in the field.

PMID- 20130358
TI  - Distribution pattern of GPRC6A mRNA in mouse tissue by in situ hybridization.
AB  - OBJECTIVE: To explore the distribution pattern of G protein-coupled receptor
      family C, group 6, subtype A (GPRC6A) mRNA in adult mice. METHODS: The
      distribution of GPRC6A mRNA in paraffin embedded adult mouse tissues was
      determined by highly sensitive nonradioactive cRNA probe in situ hybridization
      (ISH). We compared ISH with and without addition of tyramide signal amplification
      (TSA). GPRC6A wild-type and littermate GPRC6A null mice tissue sections were
      investigated by ISH. RESULTS: TSA greatly increased the sensitivity of ISH to
      detect GPRC6A mRNA in wild type mouse tissues. There was no detection of GPRC6A
      mRNA in GPRC6A gene specific knockout tissue in paraffin embedded tissue section.
      The mRNA of GPRC6A was detectable in the digestive gland or accessory digestive
      gland including salivary gland and pancreas, as well as in the tissues including
      kidney, testis, brain, muscle, and fat. CONCLUSION: The mRNA distribution pattern
      of GPRC6A gene is compatible with the phenotype of GPRC6A knockout mice.

PMID- 20130359
TI  - Prevalence and risk factors for childhood obesity in Changsha and Shenzhen in
      China.
AB  - OBJECTIVE: To determine the prevalence and the risk factors for childhood obesity
      in Changsha and Shenzhen, China. METHODS: A case-control study was conducted in
      209 obese children (the cases) identified in the investigation on childhood
      obesity in 6 288 children aged 6 to 9 years in Changsha and Shenzhen in China and
      209 children with normal weight (the controls). The cases and controls were
      matched by gender, age, and school. Adjusted odds ratio (aOR) and 95% confidence
      intervals (CI) for the risk factors were measured. RESULTS: The prevalence rate
      of overweight and obese children was 9.28% and 3.30% in Changsha, and 12.17% and
      4.22% in Shenzhen, respectively. The rate of overweight children is significantly
      higher in Shenzhen than in Changsha. No statistical difference was observed in
      the rate of obesity between the children in both cities. Paternal obesity (OR
      1.78, 95% CI 1.01 to 3.16), maternal weight gain during pregnancy>or=15.0 kg (OR
      5.22, 95% CI 2.78 to 9.80), birth weight>or=4.00 kg (OR 2.55, 95% CI 1.24 to
      5.26), unhealthy snacks>or=1 per week (OR 3.94, 95% CI 1.11 to 13.99), and
      watching television>or=2 hours per day(OR 2.35, 95% CI 1.01 to 5.47) were
      associated with childhood obesity when potential confounding factors were
      adjusted by multi-variable logistic regression analysis. CONCLUSION: Paternal
      obesity, gestational weight gain, high birth weight, and unhealthy life-style are
      important risk factors for obesity in urban children in south China.

PMID- 20130360
TI  - Brain functional connectivity of functional magnetic resonance imaging of
      patients with early-onset schizophrenia.
AB  - OBJECTIVE: To detect whether and where brain functional connectivity exists in
      the resting state of patients with early-onset schizophrenia by using functional
      magnetic resonance imaging (fMRI). METHODS: Nineteen early-onset schizophrenic
      patients were diagnosed with Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV) of American Psychiatric Association. The 19
      early-onset schizophrenic patients and another 19 healthy volunteers underwent
      fMRI in resting state. Cingulate gyrus was selected as region of interest and the
      difference was analyzed in the cingulate gyrus functional connectivity pattern
      between the 19 patients with early-onset schizophrenia (EOS) and 19 matched
      controls using resting-state fMRI. A two-sample t test was performed on the
      individual in a voxel by voxel manner. RESULTS: Statistical map was set a
      combined threshold of P<0.005 and the number of voxel>20. Functional connectivity
      in the resting state was abnormal in the patients,including decreased functional
      connectivity and increased functional connectivity. The abnormal area was
      distributed all over the brain. The brain area with decreased functional
      connectivity included bilateral posterior cerebellar lobes, superior frontal
      gyrus, middle frontal gyrus, gyrus rectus,hippocampus, cuneus gyrus,fusiform
      gyrus,middle occipital gyrus,inferior occipital gyrus, right inferior temporal
      gyrus,right middle temporal gyrus, and right angular gyrus. The brain area with
      increased functional connectivity included left middle temporal and left inferior
      temporal gyrus. CONCLUSION: Abnormal cingulate gyrus functional connectivity of
      schizophrenia might exist in the resting state. Resting state fMRI is important
      for the research of schizophrenia.

PMID- 20130361
TI  - [Diffusion tensor imaging and resting state functional magnetic resonance imaging
      on young patients with major depressive disorder].
AB  - OBJECTIVE: To explore the pathological mechanism of brain function and structure
      in young patients with major depressive disorder by diffusion tensor
      imaging(DTI)and resting state functional magnetic resonance imaging (fMRI).
      METHODS: Sixteen participants diagnosed with major depression (MD) and 16 healthy
      age and gender-matched controls(HC) were recruited. Resting state fMRI and DTI
      brain scans were performed on all participants. A voxel-based method (VBM) was
      used to analyze the DTI datasets, and regional homogeneity (ReHo) approach was
      applied to preprocess the fMRI datasets. The value of fractional anisotropy (FA)
      and ReHo maps were obtained in the whole brain. RESULTS: FA values in the MD
      group were significantly lower than those of the healthy controls in the white
      matter of the left middle temporal gyrus, right middle frontal gyrus, left medial
      frontal gyrus, right precentral gyrus, left angular gyrus, left fusiform gyrus,
      left superior temporal gyrus, right middle temporal gyrus, right sub-gyral, left
      insula, and left pyramis (P<0.01). ReHo in the MD group decreased in the left
      superior frontal gyrus, right superior frontal gyrus, left middle frontal gyrus,
      right middle frontal gyrus, left medial frontal gyrus, right medial frontal
      gyrus, left paracentral lobule, right paracentral lobule, right inferior parietal
      lobule, left postcentral gyrus, right postcentral gyrus, left middle occipital
      gyrus, left lingual gyrus, right putamen, right cingulate gyrus, right cuneus,
      left superior temporal gyrus, and right middle temporal gyrus (P<0.01).
      CONCLUSION: Abnormality of brain white microstructure and function exist widely
      in young patients with major depressive disorder. Abnormal connection of
      structures and function between the brain areas may be the key reason for the
      depression.

PMID- 20130362
TI  - [Effect of maternal deprivation on emotion and expression of dopamine transporter
      in adult rats].
AB  - OBJECTIVE: To investigate the change of emotion and striatum dopamine
      transporter(DAT) expression in adult male rats experiencing maternal deprivation,
      and to explore whether DNA methylation is involved in the regulatory mechanism of
      DAT expression. METHODS: Newborn rats were randomly divided into 2 groups: a
      maternal separation group (n=16) and a control group (n=14). The maternal
      deprivation group were separated from their mother for 6 hours (09:00-15:00) per
      day from postnatal day 1 to 14, while the controls (n=14) without the
      deprivation. When the rats in the 2 groups were 12 week, their spontaneous
      anxiety levels and exploratory ability in novel environments were assessed by an
      elevated plus maze and an open field test. DAT mRNA expression in the striatum
      was detected by reverse transcription-PCR, and its DNA methylation level was
      measured by bisulfated DNA sequencing. RESULTS: Maternally-deprived rats showed
      lower ability of exploring in a new environment and lower levels of anxiety than
      the controls. The expression of DAT mRNA in the striatum of the maternal
      separation group (0.236+/-0.043) was significantly lower than that in the control
      group (0.480+/-0.107) (P<0.05). However the DNA methylation level in the promoter
      region of DAT was not significantly different between the 2 groups. CONCLUSION:
      Maternal deprivation influenced the emotion and expression of dopamine
      transporter in adult rats and DNA methylation may not be involved.

PMID- 20130363
TI  - [Effect of RelB-silenced BMDC pulsed with Talpha146~162 on immunoreaction of T
      cells primed with TAChR].
AB  - OBJECTIVE: To investigate whether RelB-silenced bone marrow-derived dendritic
      cells (BMDC) pulsed with torpedo acetylcholine receptor (TAChR) immuno-dominant
      peptide Talpha146~162 can induce tolerance in T cells primed with TAChR. METHODS:
      Recombinant lentivirus that produced RelB siRNA and control lentivirus were
      prepared and used to infect BMDCs. The infected BMDCs were stimulated with
      LPS,and the resulting cells were designated as DC-siRelB or DC-control,
      respectively. The mRNA and protein expression of RelB were examined by
      quantitative real-time PCR and Western blot. Cell surface markers of DC were
      evaluated by flow cytometry. IL-12 in the supernatant was detected by ELISA. Mice
      were randomly divided into 6 groups: A1, A2, A3,K1, K2, and K3. On day 0, group
      A1, A2, and A3 were primed with TAChR in CFA and group K1, K2 and K3 were primed
      with KLH+CFA. On day 7, group A2 and K2 were injected with Talpha146~162 pulsed
      DC-siRelB, group A3 and K3 were injected with Talpha146~162 pulsed DC-control,
      while A1 and K1 group received PBS at the same time. On day 14, lymphocyte
      proliferative response of the 4 groups were measured. RESULTS: Recombinant
      lentivirus including RelBshRNA genes was successfully constructed. RelB siRNA
      knocked down RelB expression in BMDCs obviously. Compared with DC-control, DC
      siRelB expressed a significantly lower level of CD80, CD86, and MHC class II on
      their surface, producing lower level of IL-12. Compared with group A1 and A3,
      lymphocyte proliferative response to TAChR of A2 group was suppressed
      significantly (P<0.05). No different lymphocyte proliferative responses to KLH
      and ConA were seen in group A1, A2 and A3 (P>0.05). No different lymphocyte
      proliferative responses were seen in group K1, K2 and K3 (P>0.05). CONCLUSION:
      Lentiviral-mediated RelB-silenced BMDCs are maturation resistant and can induce
      antigen-specific tolerance in TAChR primed C57BL/6 mice,which provides a basis
      for further study of their therapeutic potential in myasthenia gravis.

PMID- 20130364
TI  - [Significance and expression of S100A9 and NMP238 in cervical carcinoma tissues
      with different concurrent chemoradiotherapy sensitivities].
AB  - OBJECTIVE: To determine the significance and expression of S100A9 and NMP238 in
      cervical carcinoma with different concurrent chemoradiotherapy sensitivities.
      METHODS: Fresh carcinoma tissues were collected from untreated cervical carcinoma
      patients and preserved at -80 degree. The tissues were classified into 2 groups:
      a high sensitivity group (HS) and a low sensitivity group (LS) according to their
      response to concurrent chemoradiotherapy. Protein was separated by 2-dimensional
      gel electrophoresis (2-DE). Peptide mass fingerprintings (PMF) were acquired by
      matrix assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) and the proteins were identified by data searching in the Mascot
      database. Differential expressed proteins were assayed by Western blot and
      immunohistochemistry. RESULTS: Most of the gels were clear and were successfully
      and reproductively analyzed. Intensity and rate of S100A9 expression were higher
      in the HS group than in the LS group,and those of NMP238 expression were higher
      in the LS group than in the HS group. CONCLUSION: S100A9 and NMP238 expression is
      associated with concurrent chemoradiotherapy sensitivity in cervical carcinoma.

PMID- 20130365
TI  - [Effect of endothelial progenitor cells on the proliferation of co-cultured
      vascular smooth muscle cells].
AB  - OBJECTIVE: To explore the effect of endothelial progenitor cells (EPCs) on the
      proliferation of co-cultured rat vascular smooth muscle cells (VSMCs). METHODS:
      Mononuclear cells were isolated from fresh cord blood by 6% hydroxyethyl starch
      (HES) and density gradient centrifugation. Isolated mononuclear cells were
      cultured in EGM-2 medium supplemented with 20% fetal bovine serum (FBS),
      VEGF,bFGF and other growth factors. Biological features of EPCs were observed at
      different time points, and EPCs were identified by morphology, fluorescence
      double-staining and flow cytometry. Indirect immunofluorescence was performed to
      analyze the expression of alpha-SM-actin, calponin of VSMCs special antigen. Co
      culture system of EPCs and VSMCs was established by transwell permeable support.
      FBS (20%) was used to stimulate the proliferation of VSMCs. In a VSMCs/EPCs co
      culture system, the DNA synthesis ability, total protein level and cell cycle of
      VSMCs were determined by BrdU marking method,protein quantitation and flow
      cytometry after co-culture for 6, 12, 24,48 and 72 h. RESULTS: After co-culture
      for 12, 24, 48, and 72 h, the DNA synthesis ability and total protein level of
      VSMCs significantly decreased compared with the control group (P<0.05). Flow
      cytometry showed that the percentage of S phase of VSMCs in VSMCs/EPCs co
      cultured group significantly decreased and the percentage of G1 phase increased
      markedly compared with the control group (P<0.05). The maximal inhibitory effect
      was observed at 48 h. CONCLUSION: Early EPCs could inhibit the proliferation of
      VSMCs.

PMID- 20130366
TI  - [Effect of hemorrhage on cell apoptosis in hippocampal CA1 region of rats under
      controlled hypotension].
AB  - OBJECTIVE: To explore the effect of hemorrhage on cell apoptosis in the
      hippocampal CA1 region of rats under controlled hypotension (CH). METHODS: A
      total of 36 Sprague Dawley rats were randomly divided into 2 groups: Group C
      (with no CH) and Group H (with CH). According to different ratios of blood loss
      to total blood volume, Group C and Group H were redivided into 6 subgroups (6 in
      each group): C1,H1 (10%); C2, H2 (20%); C3, H3 (30%). Induced by sodium
      nitroprusside and esmolol, the mean material pressure in Group H was decreased to
      50~55 mmHg and kept for 10 minutes, and then blood loss was started, keeping the
      pump speed. Without CH, the same style of hemorrhage was performed in Group C.
      The material pressure was increased 60 minutes later after the hemorrhage.
      Expression of bcl-2 and caspase-3 protein was detected by immunohistochemical
      method, and apoptosis cells were detected by TUNEL staining. RESULTS: The average
      optical density of bcl-2 and caspase-3 was higher in Group H3 than that in Group
      C3 (P<0.05). There were more apoptosis cells examined by TUNEL in Group H3 than
      in Group C3 (P<0.05). CONCLUSION: Thirty percent blood loss under controlled
      hypotension can induce cell apoptosis in hippocampal CA1 region in rats.

PMID- 20130367
TI  - [Effect of the formulae for calming the liver and suppressing YANG on lymphocyte
      proteome in migraine rats with syndrome of hyperactivity of liver-YANG].
AB  - OBJECTIVE: To explore the molecular mechanism of the formulae for calming the
      liver and suppressing YANG in migraine rat model with syndrome of hyperactivity
      of the liver-YANG. METHODS: A rat model of migraine with hyperactivity of liver
      YANG was established through electrical trigeminal ganglion stimulation and
      syndrome of oral administration of Fuzi decoction. The total proteins of the
      lymphocyte in the rats were separated by immobilized pH gradient-based 2
      dimensional gel electrophoresis (2-DE), and the 2-DE image was analyzed by
      PDQuest 7.0 software. Matrix-assisted laser desorption/ionization-time of flight
      mass spectrometry (MALDI-TOF-MS) and the SWISS-PORT and MSDB database were used
      to identify differential proteins. RESULTS: The formulae for calming the liver
      and suppressing YANG could also improve headache. Well-resolution and
      reproducible 2-DE patterns of rat lymphocyte from normal, model, and therapy
      tissues were obtained. Eleven of the total 13 differential protein spots were
      successfully identified by MALDI-TOF-MS. These proteins were alcohol
      dehydrogenase 3 (ADH3), glycogen phosphorylase, ATP synthase D chain, annexin-3,
      ubiquitin, neutrophil defensin 4 precursor, melanoma-associated antigen E2, heat
      shock protein-27, annexin-A1, peroxirdoxin-II, MU class glutathione S-transferase
      (Fragment)(GSH). CONCLUSION: Differences occur in the expression of lymphocyte
      proteins in migraine rats with syndrome of hyperactivity of liver-YANG after
      treatment with the formulae for calming the liver and suppressing YANG, and the
      11 identified protein spots may be associated with its mechanism.

PMID- 20130368
TI  - [Effect of Cordyceps Cinensis extractant on apoptosis and expression of Toll-like
      receptor 4 mRNA in the ischemia-reperfusion injured NRK-52E cells].
AB  - OBJECTIVE: To observe the apoptosis and expression of Toll-like receptor (TLR)
      4's mRNA in ischemia-reperfusion injured rat renal tubular epithelia cells (NRK
      52E) in vitro, and effect of Cordyceps Sinensis (CS) extractant. METHODS:
      Cultured NRK-52E cells were divided into a control group, a model group, and a CS
      preincubated group. All first removed media and incubated with antimycin A for 1
      h, and then recovered the media to simulate the ischemia-reperfusion injury in
      vitro. We detected the apoptosis ratio of cells by flow cytometer and the mRNA
      expression of TLR-4, Bax, Bcl-2 gene by reverse transcription-polymerase chain
      reaction at different time points. RESULTS: In ischemia-reperfusion injured NRK
      52E, the apoptosis ratio rose as time passed (P<0.05). We also observed increased
      mRNA expression of TLR-4, Bax (P<0.05) and deceased expression of Bcl-2 (P<0.05).
      Compared with the model group, the CS preincubated NRK-52E cells showed apparent
      tolerance to ischemia-reperfusion injury, which manifestated lower apoptosis
      ratio (P<0.05), decreased expression of mRNA of TLR-4, Bax and increased
      expression of Bcl-2 (All Ps<0.05). CONCLUSION: The number of apoptosis cells and
      the expression of TLR-4 mRNA increased with ischemia-reperfusion injury of NRK
      52E in vitro. CS can prevent the NRK-52E cells from ischemia-reperfusion injury
      by downregulating TLR-4 gene.

PMID- 20130369
TI  - [Establishment of 3-dimensional finite element model of human knee joint and its
      biomechanics].
AB  - OBJECTIVE: To establish a 3-dimensional (3-D) finite element knee model in
      healthy Chinese males, to verify the validity of the model, and to analyze the
      biomechanics of this model under axial load, flexion moment, varus/valgus torque,
      and internal/external axial torque. METHODS: A set of consecutive transectional
      computerized tomography images of normal male knee joints in upright weight
      bearing position was selected. With image processing and inversion technology,
      the 3-D finite element model of the normal knee joint was established through the
      software ABAQOUS/STANDARD Version-6.5.Biomechanical analysis of this model was
      processed under axial load, flexion moment, varus/valgus torque, and
      internal/external axial torque. RESULTS: A 3-D finite element model of healthy
      Chinese males was successfully established. The ranges of motion of varus and
      valgus were both small and the difference between them has no statistical
      significance (P>0.05). The motion of internal and external rotation of the knee
      took place only in flexion situation.The range of motion of external rotation was
      larger than that of internal rotation in the same knee (P<0.05). CONCLUSION: The
      3-D geometrical model of the knee resembles the actual knee segments. It can
      imitate the knee response to different loads. This model could be used for
      further study on knee biomechanics.

PMID- 20130370
TI  - [Hardy-Weinberg equilibrium in genetic epidemiology].
AB  - Hardy-Weinberg equilibrium test is the base of genetic epidemiology. The new
      methods for Hardy-Weinberg equilibrium test involve: X chromosome-linked single
      nucleotide polymorphism Hardy-Weinberg test, inbreeding coefficient (F) test, an
      incomplete enumeration algorithm for an exact test of Hardy-Weinberg proportions
      with multiple alleles, and graphical tests for Hardy-Weinberg equilibrium based
      on the ternary plot. It is necessary to conduct Hardy-Weinberg equilibrium test
      in genetic epidemiology studies and adjust the associations as deviation of Hardy
      Weinberg equilibrium occurs.

PMID- 20130371
TI  - Structural and antigenic variance between novel influenza A/H1N1/2009 and
      influenza A/H1N1/2008 viruses.
AB  - BACKGROUND: The emergence of influenza A/H1N1/2009 is alarming. The severity of
      previous epidemics suggests that the susceptibility of the human population to
      H1N1 is directly proportional to the degree of changes in hemagglutinin/HA and
      neuraminidase/NA; therefore, H1N1/2009 and H1N1/2008 were analyzed for their
      sequence as well as structural divergence. METHODOLOGY: The structural and
      sequence divergence of H1N1/2009 and H1N1/2008 strains were analyzed by aligning
      HA and NA amino acid sequences by using ClustalW and ESyPred3D software. To
      determine the variations in sites of viral attachment to host cells, a comparison
      between amino acid sequences of HA and NA glycosylation sites was performed with
      NetNGlyc software. The antigenic divergence was executed by CTL epitope
      prediction method. RESULTS: The amino acid homology levels of H1N1/2009 were
      20.32% and 18.73% compared to H1N1/2008 for HA and NA genes, respectively. In
      spite of the high variation in HA and NA amino acid composition, there was no
      significant difference in their structures. Antigenic analysis proposes that
      great antigenic differences exist between both the viral strains, but no addition
      of a new site of glycosylation was observed. CONCLUSIONS: To our knowledge, this
      is the first report suggesting that the circulating novel influenza virus
      A/H1N1/2009 attaches to the same glycosylation receptor sites as its predecessor
      influenza A/H1N1/2008 virus, but is antigenically different and may have the
      potential for initiating a significant pandemic. Our study may facilitate the
      development of better therapeutics and preventive strategies, as well as impart
      clues for novel H1N1 diagnostic and vaccine development.

PMID- 20130372
TI  - Public knowledge, attitude and behavioural changes in an Indian population during
      the Influenza A (H1N1) outbreak.
AB  - BACKGROUND: Influenza A (H1N1) is the most recent of the pandemic diseases that
      has affected the world's population. The aim of this study was to assess
      knowledge, attitude and behavioural responses of an Indian community toward
      Influenza A (H1N1). METHODOLOGY: A cross-sectional questionnaire survey was
      conducted in Udaipur (Rajasthan, India) among 791 individuals (57% males and 43%
      females) from 23 July to 27 August 2009. Outcome measures were perceived
      seriousness of the disease, opinion about government and health authorities,
      perceived efficacy of various preventive measures, avoidance behaviours, and
      increased hygiene maintenance in relation to Influenza A (H1N1). RESULTS: Of 791
      respondents, 83.1% had heard about Influenza A (H1N1), but 47.4% felt that they
      did not have enough information about the pandemic. Only 34.5% felt that their
      health would be seriously affected if they contracted Influenza A (H1N1). Over
      half of the respondents (59.6%) had no idea about the duration of the pandemic.
      Knowledge differed significantly according to gender, age groups, and educational
      status as well as working status; however, females had better attitude than
      males. Respondents rated face masks and vaccines as the most effective preventive
      measures. CONCLUSION: Results showed that in spite of having acceptable knowledge
      and attitude, behavioural response to Influenza A (H1N1) was poor. Therefore,
      increased efforts should be made by the government to understand what factors are
      associated with adaptive behaviour changes among the general public. Emphasizing
      the efficacy of recommended actions and the possible duration of the outbreak may
      further help to improve public compliance.

PMID- 20130373
TI  - Serosurvey for Toxoplasma gondii in dogs in Maiduguri, Borno State, Nigeria.
AB  - The seroprevalence of Toxoplasma gondii (T. gondii) antibodies in dogs in
      Maiduguri, the capital of Borno State, Nigeria, was determined using the Latex
      Aagglutination Test (LAT). Antibodies (LAT titer > 1:64) to T. gondii were found
      in 42 (25%) of the animals examined. Antibody titers in positive dogs ranged from
      1:64 (15 dogs) to 1:2048 (3 dogs). There was a significant statistical difference
      (P < 0.05) between age groups of dogs, the prevalence being higher in dogs > or =
      3 years (chi2 = 13.73 P = 0.0002, OR 2.80 CI95% 1.28-6.13 P = 0.008). Pure
      Alsatians and their crosses were less likely to be seropositive (OR cross breed
      0.28 CI95% 0.13-0.61 P = 0.001, OR Alsatian 0.16 CI95% 0.04-0.58 P = 0.002). The
      high prevalence of T. gondii infection that we found in dogs suggests a need for
      a larger survey to determine the national prevalence and identify possible risk
      factors in different agro-climatic zones. Such a study will help in formulating
      nation-wide control measures for toxoplasmosis.

PMID- 20130374
TI  - Multidrug-resistant and extensively drug resistant tuberculosis in Kashmir,
      India.
AB  - BACKGROUND: To study the profile of multidrug-resistant tuberculosis (MDR-TB) and
      extensively drug-resistant tuberculosis (XDR-TB) in tertiary care hospital
      setting, representing almost the whole affected population in Kashmir valley of
      India. METHODOLOGY: A total of 910 cases of pulmonary tuberculosis were enrolled
      over four years. Among these, cases of MDR-TB and XDR-TB were meticulously
      studied for drug susceptibility, treatment, adverse effects profile and overall
      survival. RESULTS: Fifty-two (5.7%) cases of MDR-TB were identified, among which
      eight (15.3%) were diagnosed as XDR-TB on the basis of drug susceptibility
      testing, using the prescribed definition. The cases were sensitive to 2, 3, 4, 5
      and more than 5 drugs in almost equal proportions. Thirty-seven (71.1%) cases
      were successfully cured; eleven (21.1%) patients died; and only four (7.6%) cases
      defaulted, indicating overall satisfactory adherence to treatment. CONCLUSION:
      For effective treatment of MDR-TB and XDR-TB, early case detection, improved
      laboratory facilities, availability of appropriate treatment regimens, and
      financial assistance in resource-limited settings through effective political
      intervention are necessary for better patient adherence and overall cure.

PMID- 20130375
TI  - Use of the cefepime-clavulanate ESBL Etest for detection of extended-spectrum
      beta-lactamases in AmpC co-producing bacteria.
AB  - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) may not always be detected
      in routine susceptibility tests. This study reports the performance of the
      cefepime-clavulanate ESBL Etest for the detection of ESBLs in Enterobacteriaceae,
      including those producing AmpC enzyme. METHODOLOGY: Consecutive non-duplicate
      isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis
      isolated from bloodstream infections from January to June 2008 were tested for
      ESBL by both the standard CLSI double-disk diffusion method using ceftazidime and
      cefotaxime disks and Etests using ceftazidime/ceftazidime-clavulanate,
      cefotaxime/cefotaxime-clavulanate and cefepime/cefepime-clavulanate gradients.
      Isolates were also tested for the presence of transferable AmpC beta-lactamase by
      AmpC disk test and the efficacies of the different Etests in detecting ESBL
      production were compared. RESULTS: A total of 113 bacterial isolates (61 K.
      pneumoniae, 50 E. coli, and 2 P. mirabilis) were recovered. Respectively, 42
      (37.2%) and 55 (48.7%) isolates were positive for ESBL by the ceftazidime
      clavulanate and cefotaxime-clavulanate combined disk tests. The cefepime/cefepime
      clavulanate Etest strip detected the maximum number of isolates (70/113, 61.9 %)
      as ESBL-positive compared to the ceftazidime/ceftazidime-clavulanate and
      cefotaxime/cefotaxime-clavulanate strips, which detected 57 (50.4%) isolates each
      as ESBL-positive. All three ESBL Etest strips were equally effective in detecting
      ESBL in the isolates that were AmpC negative. In the 66 (58.4%) isolates that co
      produced AmpC in addition to the ESBL enzymes, cefepime/cefepime-clavulanate
      Etest strip detected ESBL in an additional 13 (11.4%) isolates as compared to the
      other ESBL Etest strips. CONCLUSIONS: Cefepime-clavulanate ESBL Etest is a
      suitable substitute to test for ESBL production, especially in organisms
      producing AmpC beta-lactamases.

PMID- 20130376
TI  - Pan-resistant Acinetobacter infection in neonates in Karachi, Pakistan.
AB  - BACKGROUND: Pan-resistant Acinetobacter infection has emerged as an important
      nosocomial pathogen in our inpatient neonates over the past few years.
      METHODOLOGY: We performed a retrospective chart review during a five-year period
      (July 2003 - June 2008) of all neonates hospitalized in our neonatal intensive
      care unit (NICU) who developed Acinetobacter infection to identify mortality
      associated risk factors in Acinetobacter neonatal infection. RESULTS: During the
      five-year study period, 122 cultures from 78 neonates grew Acinetobacter. Source
      sites of positive culture were in the following descending order: blood (n = 57),
      trachea (n = 55), tissue/wound/body fluids (n = 4), eye (n = 4), urine (n = 1),
      and cerebrospinal fluid (n = 1). Twenty-four (31%) patients had Acinetobacter
      isolated from more than one site. At the time of admission the mean age was 2.08
      +/- 4 days and mean weight was 1.77 +/- 0.88 kg; 75% were premature. Pan
      resistance (87/122; sensitive only to Polymyxin) was present in 71% of
      Acinetobacter isolates. Crude mortality rate of this cohort was 47%, while 70% of
      patients died within four days after positive Acinetobacter culture. We
      identified weight of less than 1 kg on admission (p 0.06, adjusted Odds Ratio
      (AOR) 1.53), gestational age 28 weeks or less (p 0.011, AOR 2.88), poor perfusion
      (p 0.007, AOR 2.4), thrombocytopenia (p 0.01; AOR 1.6) and metabolic acidosis (p
      0.01; AOR 1.67) as predictors associated with poor outcome. CONCLUSION: Pan
      resistant Acinetobacter infection is exceedingly fatal in newborns, particularly
      in premature and very low-birth weight neonates. Rational antibiotic use and
      vigilant infection control in NICUs are key to controlling multi-drug resistant
      Acinetobacter infection and improving clinical outcome.

PMID- 20130377
TI  - The incidence, intensity and host morbidity of human parasitic protozoan
      infections in gastrointestinal disorder outpatients in Buea Sub Division,
      Cameroon.
AB  - BACKGROUND: Numerous protozoans inhibit the gastrointestinal tract of humans with
      the majority being either non-pathogenic commensals or of a type that may result
      in mild disease. However, some of these organisms can cause severe diseases under
      certain circumstances while others may become highly virulent and invasive
      causing potentially lethal systemic disease. This study investigated the
      prevalence, intensity and host morbidity of human intestinal protozoan infections
      in individuals living in the Buea Sub-Division, Cameroon. METHODOLOGY: Random
      sampling was used to collect stool samples from 356 patients in a cross-sectional
      study. All samples were examined by formol-ether concentration and direct smear
      techniques. Data collected was analyzed and differences in proportions were
      determined using the Chi square (chi(2)) test, Fisher's exact test, or analysis
      of variance where appropriate. RESULTS: It was found that 28.1% (100/356) of the
      sampled population were infected with protozoans. Females showed a higher
      infection rate (29.7%; 56/182) than males (26.4%; 46/174) and there was a
      significantly (P < 0.001) higher prevalence in rural areas (38.7%; 55/142) than
      in urban areas (21.0%; 45/214). The 6 to 12 years age group had a significantly
      (P < 0.05) higher infection rate (42.9%; 30/70). The total prevalence of
      intestinal protozoans was as follows: E. histolytica (24.4%), E. coli (11.2%) and
      G. lamblia (0.6%). The most prevalent morbidity effects associated with
      intestinal protozoan infections were abdominal pains, dysentery and body
      weakness. CONCLUSIONS: Since human intestinal parasitic infections are high in
      the study area, mass treatment of people with intestinal protozoans is strongly
      recommended, especially in the rural areas where the prevalence was very high.

PMID- 20130378
TI  - Is low birth weight a risk indicator for congenital cytomegalovirus infection?
AB  - BACKGROUND: Congenital cytomegalovirus infection is currently the leading cause
      of congenital infection in 0.2-2.2% of live births worldwide leading to variable
      serious sequalae. The aim of the study was to determine if low birth weight is an
      indicator of CMV congenital infection evidenced by detecting CMV-DNA in umbilical
      cord blood at the time of delivery. METHODOLOGY: CMV-IgG and IgM antibodies and
      CMV-DNAemia were assessed in umbilical cord blood of two hundreds newborns, one
      hundred of whom had birth weight < or = 2700 gram and/or head circumference < or
      = 32 cm. RESULTS: CMV-IgM was not detected, while CMV-IgG was positive in 80-90%
      of the two hundreds tested newborns. CMV-DNA was detected in four out of the 200
      newborns. One of them was over the adopted weight limit (> 2700 gram).
      CONCLUSIONS: CMV-IgM and IgG antibodies assessment was not a potential
      discriminative test to identify congenitally infected newborns. In addition, low
      birth weight and small head circumference at birth failed to predict congenital
      CMV infection. CMV-DNA detection in umbilical cord blood at the time of delivery
      using real-time PCR of all newborns is recommended as decisive, rapid and non
      invasive test.

PMID- 20130379
TI  - Co-infections due to leptospira, dengue and hepatitis E: a diagnostic challenge.
AB  - A case of mixed infection due to leptospira, dengue and hepatitis E is reported.
      Similar clinical presentation and simultaneous transmission of these diseases
      during rainy season can cause substantial misdiagnosis. Serological tests play a
      mainstay in diagnosis. Early detection by appropriate serological tests and
      institution of therapy is crucial and life saving.

PMID- 20130380
TI  - Unusual mode of transmission of dengue.
AB  - Dengue is the most important tropical mosquito-borne infectious disease caused by
      an arbovirus, the dengue virus. It should be noted that there are still other
      unusual modes of transmission of dengue infection. This paper summarizes those
      non vector-borne transmissions of dengue including vertical transmission,
      transfusion related transmission, transplantation related transmission, and
      needle-stick-related transmission.

PMID- 20130381
TI  - Neonatal septicemia isolates and resistance patterns in a tertiary care hospital
      of North India.
AB  - BACKGROUND: Septicemia continues to be a major cause of neonatal mortality and
      morbidity worldwide. METHODOLOGY: To know the rate of neonatal septicemia in our
      tertiary care centre, a retrospective analysis of 2,247 blood samples was done
      over a period of four years and three months (July 2003 to October 2007).
      RESULTS: During that period, a total of 296 (13.17%) blood samples were found to
      be positive for bacterial isolates. Gram-negative septicemia (80.40%) was
      identified in more cases than Gram-positive septicemia (20.60%) with Klebsiella
      species 84 (28.3%) being the most common isolate. Maximum resistance among Gram
      negative organisms was seen in amoxycillin/ampicillin and third-generation
      cephalosporins. Amikacin, cefoperazone/sulbactam and imipenem were found to be
      good alternative drugs. Among Gram-positive organisms, all strains were sensitive
      to Vancomycin. CONCLUSION: Continued surveillance for various pathogens and their
      susceptibility profile should be done to effectively and timely treat the
      patients of neonatal septicaemia.

PMID- 20130382
TI  - First report of CTX-M-14 producing clinical isolates of Salmonella serovar
      Typhimurium from Egypt.

PMID- 20130383
TI  - High prevalence of potential drug-drug interactions for psoriasis patients
      prescribed methotrexate or cyclosporine for psoriasis: associated clinical and
      economic outcomes in real-world practice.
AB  - BACKGROUND: Methotrexate (MTX) and cyclosporine (CYC) may adversely interact with
      common medications in patients with psoriasis. OBJECTIVE: Our purpose was to
      investigate the prevalence and outcomes of MTX/CYC polypharmacy. METHODS: We
      evaluated rates of events that may be associated with drug-related toxicity,
      health care resource utilization and costs for patients with psoriasis in the
      Ingenix(R) Impact National Managed Care Database (1999-2007) who were exposed or
      not exposed to potential drug-drug interactions. RESULTS: Among 4,583 (57.6%)
      exposed and 3,372 (42.4%) nonexposed patients, nonsteroidal anti-inflammatory
      drugs and antibiotics were the most common drugs with potential interactions. The
      exposed patients had significantly greater risks of developing renal [adjusted
      odds ratio (OR): 2.58; p = 0.0145], gastrointestinal (OR: 1.36; p = 0.0197) and
      pulmonary events (OR: 1.20; p = 0.0470), and significantly greater health care
      resource utilization (e.g. OR for inpatient and emergency department visits:
      1.47; p < 0.0001) and costs (adjusted incremental cost: USD 1,722; p < 0.0001).
      CONCLUSIONS: MTX/CYC polypharmacy is prevalent in patients with psoriasis and
      associated with significant risks.

PMID- 20130384
TI  - Linear IgA disease: successful application of immunoadsorption and review of the
      literature.
AB  - Linear IgA disease (LAD) is an autoimmune subepidermal blistering disorder
      characterized by IgA autoantibodies at the dermal-epidermal junction.
      Conventional first-line treatments include dapsone with or without oral
      glucocorticosteroids. Various other therapeutic approaches have been used in
      refractory patients. Immunoadsorption (IA) has been previously successfully
      applied in severe and/or otherwise treatment-resistant IgG-mediated immunobullous
      disorders. Here, we report a patient with a severe generalized LAD in whom
      adjuvant tryptophan IA was associated with rapid healing of skin lesions. Our
      observation suggests that IA may also be a helpful adjuvant treatment option for
      severe LAD.

PMID- 20130385
TI  - Intravesical mitomycin-C-induced interstitial pneumonia.
AB  - An 84-year-old man with no evidence of pre-existing interstitial pneumonia
      developed fatal interstitial pneumonia and respiratory failure that could only be
      explained as an adverse effect of intravesical mitomycin C chemotherapy. He had
      undergone transurethral resection of bladder cancer 3 times, followed by
      intravesical mitomycin C chemotherapy 1 month later. He had received intravesical
      mitomycin C chemotherapy every week for 2 months, and he had complained of
      dyspnea on exertion 5 days before the last intravesical mitomycin C chemotherapy
      session. Interstitial infiltration was detected in both the upper and lower lobes
      of the left lung on the day of the last instillation of mitomycin C. Despite
      discontinuation of mitomycin C and administration of methylprednisolone, his
      condition deteriorated and he died. Diagnostic evaluation of other causes of
      pneumonia, including infection and collagen-vascular diseases, was negative. The
      autopsy demonstrated diffuse alveolar damage in the lung; there were no
      remarkable findings in other organs. To our knowledge, this is the first
      pathologically confirmed case of fatal interstitial pneumonia due to intravesical
      mitomycin C chemotherapy.

PMID- 20130386
TI  - Ovarian organogenesis in mammals: mice cannot tell us everything.
AB  - The mammalian ovary shows extensive variation mainly in relation to the
      interstitial tissue of the ovary, the so-called interstitial gland, and the
      degree of gonad regionalisation, which implies the existence of a cortex and a
      medulla. Three mammalian species, mouse, human, and mole, have been reviewed here
      as representative animal models for ovarian variability. Whereas the human ovary
      may be considered to have a conventional pattern of development, the mouse and
      the mole represent the two extremes of the variation range. The mouse is
      exceptional among mammals because ovarian regionalisation is much less relevant
      than in other species. Contrarily, the mole ovary is very similar to that of
      humans regarding the cortical region, but shows a testis-like pattern of
      development in the medullary region. Thus, the mole ovary is in fact an
      ovotestis, a phenomenon also described in other mammals. Accordingly, current
      studies on the development of the mouse ovary are not sufficient to understand
      the process in a more general context, because ovarian organogenesis is
      exceptionally simple in the mouse. From an evolutionary perspective, mammals show
      a tendency to eliminate or reduce gonad regionalisation, in contrast with the
      situation in other vertebrates, where this trait has been preserved. Since
      developmental variants may not be associated with particular taxonomic groups,
      their origin seems to be adaptive rather than phylogenetic. The demonstration
      that gonad development is a rather plastic process in mammals helps to explain
      how some mammals could have evolved towards more primitive gonad developmental
      models in response to selective pressure.

PMID- 20130387
TI  - Modeling thermal influence on animal growth and sex determination in reptiles:
      being closer to the target gives new views.
AB  - Many species of oviparous reptiles, including crocodilians, a majority of
      turtles, some lizards and the 2 closely related species of Sphenodon have been
      shown to display temperature-dependent sex determination (TSD). Whereas it has
      been demonstrated very early that TSD also occurs in natural conditions, the
      relationship between a time series of changing temperatures and sex ratio remains
      a challenging problem for reptiles. We describe how a physiological model of
      embryo growth, gonadal development and aromatase activity can produce outputs
      that mimic well TSD. We provide an enhancement of a previously published model
      taking into account direct effect of temperature on aromatase activity. The
      comparison between the original model and the new one suggests that aromatase
      expression is controlled by a repressor factor expressed at masculinizing
      temperatures rather than its enhancement at feminizing temperatures.

PMID- 20130388
TI  - The aromatase inhibitor fadrozole and the 5-reductase inhibitor finasteride
      affect gonadal differentiation and gene expression in the frog Silurana
      tropicalis.
AB  - Aromatase (cyp19) and the 5alpha- and 5beta-reductases (srd5alpha and srd5beta)
      are important enzymes for vertebrate sexual development. We investigated the
      effects of inhibition of cyp19 by fadrozole (FAD), and srd5alpha and srd5beta by
      finasteride (FIN) during anuran larval development. Chronic exposures of Silurana
      (Xenopus) tropicalis from Nieuwkoop-Faber stage 12 until stage 60 were performed
      using either 2 microM FAD or 25 microM FIN. Histological analysis of exposed
      metamorphic frogs revealed that both treatments induced intersex individuals
      (presence of testicular oocytes). FAD treatment resulted in 55% male, 30% female
      and 15% intersex, while FIN treatment produced 27% male, 53% female and 20%
      intersex. Real-time RT-PCR analysis of hepatic sex steroid- and thyroid hormone
      related gene expression demonstrated that FAD-induced intersex animals had higher
      srd5alpha1, srd5alpha2 and eralpha mRNA levels than control and FAD males. In
      contrast, FIN-induced intersex had low srd5alpha1, srd5alpha2, srd5beta and dio3
      and high dio2 mRNA levels. FIN-treated males exhibited high trbeta, dio2 and a
      lower dio3 mRNA levels. We conclude that chemically induced intersex animals
      display different gene expression profiles than non-exposed animals and that,
      although morphologically similar, intersex animals produced by different
      chemicals have different endocrine pathophysiologies.

PMID- 20130389
TI  - Umbilical arterial necrotic vasculopathy associated with fetal ascites.
AB  - Immune and nonimmune neonatal ascites may be part of hydrops fetalis or may be an
      isolated finding. However, a significant percentage of nonimmune ascites do not
      have an identifiable pathogenesis and are considered idiopathic. We report a case
      of fetal ascites and umbilical arterial necrotic vasculopathy, an association not
      previously described.

PMID- 20130390
TI  - Effect of chordin-like 1 on MC3T3-E1 and human mesenchymal stem cells.
AB  - Since the discovery that bone morphogenetic proteins (BMPs) are able to induce
      ectopic bone formation, considerable effort has been devoted to apply it for bone
      regeneration. BMP activity needs to be temporally and spatially controlled and
      the organism has devised ways to achieve it. Here we show that the BMP inhibitor
      chordin-like 1 can interfere with BMP2 signalling thereby affecting the
      osteogenic differentiation of MC3T3-E1 cells. Besides its function as a BMP
      antagonist, chordin-like 1 enhanced the proliferation of human mesenchymal stem
      cells (hMSCs) in a BMP2-independent manner. When MC3T3-E1 cells were exposed to
      recombinant chordin-like 1 there was an inhibition of alkaline phosphatase (ALP)
      expression, whereas in the case of hMSCs no effect was observed. However, chordin
      like 1 dose-dependently increased the proliferation of hMSCs. This effect is
      probably BMP2 independent because the chordin-like 1 concentration that
      stimulates proliferation does not interfere with BMP signalling monitored by a
      Smad-dependent reporter gene. Our data point towards a novel, BMP-independent
      role of chordin-like 1 in hMSC proliferation.

PMID- 20130391
TI  - Diabetes induced changes in rat mesenchymal stem cells.
AB  - Diabetes mellitus, the single most important cause of vascular disease in the
      industrialized world, is also associated with bone loss and impaired fracture
      healing. Mesenchymal stem cells (MSCs) have the potential to differentiate into
      osteoblasts, chondrocytes and adipocytes and other mesenchymal cells and play a
      central role in bone formation and repair. Because of this, we have investigated
      the possibility that diabetes has direct effects on MSCs in vivo and that this
      might represent a cellular basis for diabetes-induced osteoporosis. We isolated
      MSCs from rats with streptozotocin-induced diabetes and analysed them ex vivo for
      their ability to proliferate and differentiate in the fibroblastic colony-forming
      unit assay. Effects of diabetes on bone metabolism in vivo were determined by
      analysing tibiae from control and diabetic animals by quantitative computerized
      tomography. The total number of colonies and osteoblastic colonies staining
      positive for alkaline phosphatase were quantified and both colony size and number
      were found to be significantly reduced in diabetic rats. The changes appear to be
      mediated by the induction of apoptosis and senescence by advanced glycation end
      products (AGEs), together with an increase in the receptor for AGEs (RAGE). These
      changes were paralleled by extensive loss of trabecular bone in the tibiae of the
      diabetic animals. These data suggest that MSCs become exhausted during diabetes
      and lose their differentiation potential, leading to a net loss of trabecular
      bone. Therefore, direct effects on MSCs may be responsible for some of the
      orthopaedic effects associated with diabetes.

PMID- 20130392
TI  - Sleep, immunity, and circadian clocks: a mechanistic model.
AB  - The lack of sufficient amounts of sleep is a hallmark of modern living, and it is
      commonly perceived that in the long run this makes us sick. An increasing amount
      of scientific data indicate that sleep deprivation has detrimental effects on
      immune function. Conversely, immune responses feedback on sleep phase and
      architecture. Several studies have investigated the impact of short-term sleep
      deprivation on different immune parameters, whereas only a few studies have
      addressed the influence of sleep restriction on the immune system. In many cases,
      sleep deprivation and restriction impair immune responses by disrupting circadian
      rhythms at the level of immune cells, which might be a consequence of disrupted
      endocrine and physiological circadian rhythms. Little is known about the
      mechanisms underlying the circadian regulation of immunity, but recent studies
      have suggested that local as well as central circadian clocks drive the rhythms
      of immune function. In this review, we present a mechanistic model which proposes
      that sleep (through soluble factors and body temperature) primes immune cells on
      the one hand, and, on the other hand, provides a timing signal for hematopoietic
      circadian clocks. We hypothesize that chronic sleep disruption desynchronizes
      these clocks and, through this mechanism, deregulates immune responses.

PMID- 20130393
TI  - Novel markers of left ventricular hypertrophy in uremia.
AB  - AIMS: Left ventricular hypertrophy (LVH) is the most frequent cardiac
      complication in chronic renal disease. Previous studies implicate elevated serum
      phosphorus as a risk factor for LVH. METHODS: We treated 5/6 nephrectomized rats
      with enalapril or enalapril + sevelamer carbonate for 4 months to determine if
      sevelamer carbonate had an additional beneficial effect on the development of LVH
      and uremia-induced left ventricle (LV) remodeling. RESULTS: Uremia increased LV
      weight and cardiomyocyte size. Enalapril and enalapril + sevelamer blunted the
      increase in left ventricular weight. Only enalapril + sevelamer diminished the
      increase in cardiomyocyte size. Uremia increased cyclin D2 and PCNA and decreased
      p27 protein expression in the heart. Enalapril + sevelamer diminished the
      decrease in p27 expression caused by uremia. Uremia increased Ki67-positive and
      phosphohistone H(3)-positive interstitial cells. This was not seen in
      cardiomyocytes. Multivariable regression analysis showed that increased
      phosphorus was an independent risk factor for both increased LV weight and
      cardiomyocyte size. CONCLUSIONS: These data suggest left ventricular remodeling
      consists of cardiomyocyte hypertrophy and interstitial cell proliferation, but
      not cardiomyocyte proliferation. p27 and cyclin D2 may play important roles in
      the development of LVH. In addition, phosphorus can be an independent risk factor
      for the development of LVH.

PMID- 20130394
TI  - Stress and survival pathways in the mammalian cochlea.
AB  - Studies conducted over the last few years demonstrated that signaling pathways
      that operate in the organs of Corti (OC) play a central role in survival and
      death of hair cells. An important goal of molecular otology is to characterize
      these signaling pathways in normal inner ears and inner ears exposed to a variety
      of different forms of stress, such as ototoxic substances and noise overexposure.
      In this study, we used high-performance reverse protein microarray technology and
      phospho-specific antibodies to examine the activation status of defined molecules
      involved in cellular signaling. We demonstrate that reverse protein microarrays
      based on the highly sensitive planar-waveguide technology provide an effective
      and high-throughput means to assess the activation state of key molecules
      involved in apoptotic and prosurvival signaling in microdissected OC explants
      over time. In this study, we show that gentamicin and a specific NF-kappaB
      inhibitor increase the ratio of phospho-c-Jun/c-Jun in OC explants of postnatal
      rats soon after exposure to these drugs. In addition, we found a decrease in the
      phospho-Akt/Akt ratio in OC explants early after NF-kappaB inhibition. Finally,
      we observed an early and consistent decrease in the phospho-p38/p38 ratio in OC
      explants exposed to the NF-kappaB inhibitor and only a transient decrease in this
      ratio in OC examples after gentamicin exposure.

PMID- 20130395
TI  - Modern classification of acute kidney injury.
AB  - Acute kidney injury (AKI) is a common clinical syndrome defined as a sudden onset
      of reduced kidney function manifested by increased serum creatinine or a
      reduction in urine output. This clinical syndrome has been called by 25 different
      names and at least 35 definitions. As a result of this deficiency of standardized
      definition, reported incidences of AKI in the ICU range from 1 to 25% with
      mortality rates between 15 and 60%. This lack of a uniform definition not only
      leads to the conflicting reports in the literature but is also a major obstacle
      for research in the field. The recent consensus definition which was proposed by
      the ADQI group and expanded by AKIN has brought the RIFLE criteria and staging
      into position as the standard definition and diagnosis of this syndrome. The
      RIFLE criteria have been extensively validated in more than 550,000 patients
      worldwide.

PMID- 20130396
TI  - Role of cardiac multidetector computed tomography in acute ischemic stroke: a
      preliminary report.
AB  - BACKGROUND AND PURPOSE: Cardiac multidetector computed tomography (MDCT) is less
      dependent upon the patient's condition and may be valuable in the diagnosis of
      embolic sources when the patient's cooperation is limited due to a neurologic
      deficit. However, its role has never been validated in acute stroke patients
      whose stroke mechanism is assumed to be embolic. METHODS: Consecutive patients
      who were admitted with acute ischemic stroke from May 1, 2007 to November 30,
      2007 were included in this study. Inclusion criteria were (1) any cardiac
      evidence of high-risk embolic sources for cerebral embolism, or (2) radiological
      or (3) clinical evidence of embolic stroke. All patients underwent transthoracic
      echocardiography first, and then cardiac MDCT or transesophageal echocardiography
      (TEE) was attempted, if possible. The results and feasibility of cardiac MDCT and
      TEE were compared. RESULTS: One hundred and forty-three patients met the
      inclusion criteria. Cardiac MDCT was performed in 124 patients (86.7%), TEE in 83
      patients (57.3%), whereas 75 patients (52.4%) underwent both studies. Renal
      insufficiency for cardiac MDCT and lack of cooperation for TEE were found to be
      the most impeding factors. Among the patients with both evaluations, cardiac MDCT
      identified a high-risk intracardiac embolic source in 8 and an extracardiac
      source in 20, while TEE found an intracardiac source in 1 and an extracardiac
      source in 7. Statistically significant differences were found with respect to
      detecting cardioembolic sources and high-risk aortic atheroma. CONCLUSIONS:
      Cardiac MDCT is a feasible and accurate diagnostic tool for embolic sources in an
      acute stroke setting.

PMID- 20130397
TI  - Variation in the frequency of intracerebral haemorrhage and ischaemic stroke in
      China: a national, multicentre, hospital register study.
AB  - BACKGROUND: Intracerebral haemorrhage (ICH) accounts for about one third of all
      strokes in China, a proportion that is three times higher than in Western
      populations. We aimed to determine the frequency distribution of ICH in China.
      METHODS: Using the ChinaQUEST hospital register database, the proportional
      frequency of ICH was determined by region and city location. Linear regression
      analysis was then performed to evaluate associations between the frequency of ICH
      and distribution of risk factors by city. RESULTS: Proportional frequency of ICH
      was 25% overall, but varied markedly across major geographical regions ranging
      from 11 to 36%. The differences between cities were even more profound, with the
      age- and sex-standardised proportional frequencies ranging from 5% in Guangzhou
      to 55% in Baoji. Significant associations were found between the proportional
      frequency of ICH and history of diabetes, hyperlipidaemia, and a high body mass
      index. Notably, cities with higher frequencies of diabetic, hyperlipidaemic or
      overweight individuals tended to have lower frequencies of ICH. CONCLUSIONS:
      Considerable interregional variation in the distribution of ICH in China can be
      partially explained by differences in distribution of risk factors in the
      population.

PMID- 20130398
TI  - Differential pathophysiological mechanisms of stroke evolution between new
      lesions and lesion growth: perfusion-weighted imaging study.
AB  - BACKGROUND: Stroke evolution frequently occurs during the first week after
      stroke. However, the association between the type of stroke evolution and
      baseline perfusion severity has not been investigated. METHODS: We analyzed
      clinical and serial MRI data on patients with acute middle cerebral artery
      infarcts. Multimodal MRIs were acquired before treatment and on day 7. Time to
      peak (T(max)) perfusion lesion maps were then generated, and changes in the day 7
      diffusion-weighted imaging (DWI) were classified; new lesions were defined as new
      DWI lesions not contiguous with initial abnormalities, and infarct growth as
      enlargement of DWI lesions. RESULTS: Among 74 patients (mean age 64.2 years), 51
      received recanalization therapy. The day 7 DWI revealed the presence of new
      lesions in 39 cases (52.7%) and infarct growth (mean +/- SD 20.0 +/- 4.3 ml) in
      52. No correlation was observed between new lesion and infarct growth (r = 0.029,
      p = 0.805). Most new lesions were multiple and small, located in
      cortical/superficial areas and within the mild perfusion delay (2 <or= T(max) < 4
      s) regions, whereas infarct growth generally occurred within the severer
      perfusion delay regions. Multiple regression analysis revealed that large mild
      perfusion delay was independently associated with new lesions, whereas large
      initial DWI lesions and a severer perfusion delay (4 <or= T(max) < 8 s) were
      associated with infarct growth. In terms of treatment, endovascular therapy was
      associated with new lesions, whereas the degree of angiographic recanalization
      was inversely associated with infarct growth. CONCLUSIONS: The types of stroke
      evolution differed depending on the baseline hypoperfusion severity, and the mode
      and effect of recanalization therapy. A poor correlation was observed between new
      lesions and infarct growth.

PMID- 20130399
TI  - Wake-up stroke: clinical and neuroimaging characteristics.
AB  - BACKGROUND: Approximately 25% of ischemic stroke patients awaken with
      neurological deficits. In these patients, in whom the time from symptom onset is
      uncertain, brain imaging is a potential strategy to characterize the ischemia
      duration and the presence of salvageable brain tissue. METHODS: We prospectively
      evaluated consecutive patients with acute ischemic stroke. CT angiography and CT
      perfusion (CTP) were performed in patients within 24 h of symptom onset. The
      patients were classified into 'known onset', 'indefinite onset but not on
      awakening' and 'wake-up stroke' groups. RESULTS: Of 676 patients evaluated, 420
      had known-onset strokes, 131 wake-up strokes and 125 strokes with an indefinite
      time of symptom onset. Ischemic lesion volumes were higher in patients with
      indefinite-onset strokes (p = 0.04). The frequencies of CTP mismatch and of large
      vessel intracranial occlusions were similar among the groups (p = 0.9 and p =
      0.2, respectively). CONCLUSION: The considerable prevalence of CTP mismatch and
      of intracranial artery occlusions in our patients with wake-up strokes suggests
      that arterial and perfusion imaging might be particularly important in this
      population. Revised indications for thrombolysis by using imaging-based protocols
      might offer these patients the prospect of receiving acute stroke treatment even
      without a clear time of symptom onset.

PMID- 20130400
TI  - Postcarotid endarterectomy improvement in cognition is associated with resolution
      of crossed cerebellar hypoperfusion and increase in 123I-iomazenil uptake in the
      cerebral cortex: a SPECT study.
AB  - BACKGROUND: The purpose of the present study was to investigate whether
      resolution of crossed cerebellar hypoperfusion (CCH) and increase in (123)I
      iomazenil (IMZ) uptake in the ipsilateral cerebral cortex after carotid
      endarterectomy (CEA) are associated with postoperative improvement of cognitive
      function. METHODS: Neuropsychological testing was performed preoperatively and
      after 1 postoperative month in 79 patients undergoing CEA for ipsilateral
      internal carotid artery stenosis (>or=70%). Brain perfusion single photon
      emission computed tomography (SPECT) using N-isopropyl-p-(123)I-iodoamphetamine
      and (123)I-IMZ SPECT were also performed before and after surgery. Data were
      analyzed using a three-dimensional stereotaxic region of interest template.
      RESULTS: Seven patients (9%) showed improvement in postoperative cognitive
      function. All the 7 patients exhibited both postoperative increase in blood flow
      in the ipsilateral cerebral cortex and resolution of CCH. Five patients (6%) had
      a postoperative hemispheric increase in (123)I-IMZ uptake, and cognitive function
      improved in all of these 5 patients. Analysis by a receiver operating
      characteristic (ROC) curve was used to estimate the ability to discriminate
      between patients with and without postoperative cognitive improvement. The area
      under the ROC curve was significantly greater when analyzing the magnitude of
      postoperative resolution of CCH (0.991; 95% CI 0.984-1.001) or postoperative
      hemispheric increase in (123)I-IMZ uptake (0.981; 95% CI 0.972-0.999) when
      compared with the magnitude of postoperative increase in cerebral blood flow
      (0.929; 95% CI 0.886-0.971) (p < 0.05). CONCLUSIONS: Resolution of CCH and
      increase in (123)I-IMZ uptake in the ipsilateral cerebral cortex after CEA is
      associated with postoperative improvement in cognitive function. These results
      may indicate that cognitive impairment is related to a state of potentially
      reversible central benzodiazepine receptor downregulation in the cortex in
      response to transient ischemic attack or minor stroke.

PMID- 20130401
TI  - Very early rehabilitation or intensive telemetry after stroke: a pilot randomised
      trial.
AB  - BACKGROUND: Stroke patients are more likely to make a good recovery if they
      receive care in a well-organised stroke unit. However, there are uncertainties
      about how best to provide such care. We studied 2 key aspects of early stroke
      unit care: early active mobilisation (EM) and automated monitoring (AM) for
      physiological complications such as hypoxia. METHODS: This was an observer
      blinded, factorial (2 x 2) pilot randomised controlled trial recruiting stroke
      patients within 36 h of symptom onset. The patients were randomised to 1 of 4
      nurse-led treatment protocols: (a) standard stroke unit care, (b) EM, (c) AM or
      (d) combined EM and AM. The primary outcome was the Rankin score at 3 months. We
      also report the data on feasibility and safety. RESULTS: We randomised 32
      patients (mean age = 65 years; mean baseline modified NIH score = 6). On
      unadjusted comparisons, the EM patients were significantly (p < 0.05) more likely
      to mobilise very early (within 1 h of randomisation) and to achieve walking by
      day 5 and were less likely to develop complications of immobility. The AM group
      was significantly (p < 0.05) more likely to have pre-defined physiological
      complication events detected. All these associations remained, but were less
      statistically significant, after correcting for age, baseline NIH score and co
      interventions. There were no significant safety concerns. DISCUSSION: We have
      demonstrated the feasibility of implementing EM and AM for physiological
      complications in a randomised controlled trial. Larger trials are warranted to
      determine whether these interventions have clinical benefits.

PMID- 20130402
TI  - Relationships between fluoride intake, urinary fluoride excretion and fluoride
      retention in children and adults: an analysis of available data.
AB  - The aim of this study was to examine the relationship between total daily
      fluoride intake (TDFI), daily urinary fluoride excretion (DUFE) and fractional
      fluoride retention (FFR) using available data, in order to clarify the ability of
      DUFE to predict TDFI and, therefore, the risk of fluorosis development.
      Examination of published reports of simultaneous measurement of TDFI and DUFE,
      together with data from two unpublished Chilean studies, yielded data for 212
      children aged less than 7 years and for 283 adults aged 18-75 years, providing a
      total of 212 and 269 data points, respectively. The relationship between DUFE and
      TDFI was studied for children and adults, separately. Daily fluoride retention
      (DFR) was estimated as a function of TDFI in children and adults assuming an
      average 90% fluoride absorption, and the numerical relationships between the
      estimated FFR and the TDFI were explored. Limiting FFR values of 0.55 and 0.36
      were found for children and adults, respectively, above a threshold of TDFI of
      0.5 and 2 mg, respectively. Neutral fluoride balances were predicted when the
      TDFI was equal to approximately 0.07 mg F/day for children and 0.8 mg F/day for
      adults. For children and adults, it is possible to obtain reasonably good
      estimations of community-based TDFI and DFR, using DUFE data. The advantages and
      limitations of these relationships, together with the need for future studies,
      are discussed.

PMID- 20130403
TI  - Modelling childhood caries using parametric competing risks survival analysis
      methods for clustered data.
AB  - Caries in primary teeth is an ongoing issue in children's dental health. Its
      quantification is affected by clustering of data within children and the
      concurrent risk of exfoliation of primary teeth. This analysis of caries data of
      103,776 primary molar tooth surfaces from a cohort study of 2,654 British
      children aged 4-5 years at baseline applied multilevel competing risks survival
      analysis methodology to identify factors significantly associated with caries
      occurrence in primary tooth surfaces in the presence of the concurrent risk of
      exfoliation, and assessed the effect of exfoliation on caries development.
      Multivariate multilevel parametric survival models were applied at surface level
      to the analysis of the sound-carious and sound-exfoliation transitions to which
      primary tooth surfaces are subject. Socio-economic class, fluoridation status and
      surface type were found to be the strongest predictors of primary caries, with
      the highest rates of occurrence and lowest median survival times associated with
      occlusal surfaces of children from poor socio-economic class living in non
      fluoridated areas. The concurrent risk of exfoliation was shown to reduce the
      distinction in survival experience between different types of surfaces, and
      between surfaces of teeth from children of different socio-economic class or
      fluoridation status. Clustering of data had little effect on inferences of
      parameter significance.

PMID- 20130404
TI  - Has dental caries prevalence some connection with caries index values in adults?
AB  - DMF index values have been used for 70 years and were originally meant to
      describe both dental status and treatment need in elementary school children.
      Since then its application to caries experience and severity determination has
      expanded. Today, WHO has standardized its use in oral health surveys in
      describing past and present caries experience in adults and the elderly as well.
      This expansion to all age cohorts creates some problems if the index is limited
      to dental caries, which can be easily avoided when individual values are not
      combined. This has been performed in some of the 7,187 DMF index publications
      included in PubMed. The high number of scientific articles using this index
      underlines its leading role in the present epidemiological caries research. On
      the other hand, WHO uses different determinations for clinical dental caries and
      missing teeth in ICD-10, the 10th revision of International Classification of
      Diseases, which does not include dental restorations. Combining the individual
      parameters of Oral Health Surveys and diseases of ICD-10, and analyzing the mean
      value of each parameter separately, will give a precise picture of dental health
      at different ages.

PMID- 20130405
TI  - Diabetes is associated with increased rate of cognitive decline in questionably
      demented elderly.
AB  - BACKGROUND: This study examines whether the association of diabetes with the rate
      of cognitive decline varies according to dementia severity. METHODS: Longitudinal
      study on subjects residing in nursing homes and assisted living (n = 342). The
      Mini Mental State Examination (MMSE) was used to measure the rate of cognitive
      decline in diabetic and nondiabetic subjects who were nondemented (Clinical
      Dementia Rating, CDR = 0; n = 125), questionably demented (CDR = 0.5; n = 58) or
      frankly demented (CDR > or =1; n = 89) at baseline. Diagnosis of diabetes was
      ascertained by review of medical records and history. RESULTS: Diabetes was
      associated with an increased rate of decline in the MMSE score of questionably
      demented subjects (p < 0.0001). In frankly demented subjects, diabetes tended to
      be associated with less cognitive decline (p = 0.04). Diabetes was not associated
      with the rate of MMSE decline in nondemented subjects (p = 0.89). CONCLUSION: In
      individuals with questionable dementia (CDR = 0.5), diabetes is associated with a
      faster rate of cognitive decline as measured by the MMSE, but not in nondemented
      (CDR = 0) or frankly demented (CDR > or =1) individuals.

PMID- 20130406
TI  - Neuropsychiatric symptoms in korean patients with Alzheimer's disease:
      exploratory factor analysis and confirmatory factor analysis of the
      neuropsychiatric inventory.
AB  - BACKGROUND/AIMS: We designed this study to examine subsyndromes in Korean
      patients with Alzheimer's disease (AD) using exploratory factor analysis (EFA)
      and confirmatory factor analysis (CFA). METHODS: Initial participants were 778 AD
      patients recruited from the Clinical Research Center for Dementia of South Korea
      and assessed via the Korean Neuropsychiatric Inventory. Those with > or =1
      neuropsychiatric symptom were randomly divided into groups. Principal axis
      factoring with oblimin rotation was used to analyze group 1 inventory results,
      and maximum likelihood estimation extraction with Bollen-Stine bootstrapping was
      used for group 2. RESULTS: The results of the EFA showed the presence of 4
      subsyndromes: hyperactivity, affect, psychosis and apathy/vegetative symptom. The
      CFA results indicated this model was the best-fitting model for explaining these
      subsyndromes. CONCLUSION: Our model showed the best fit and identified 4
      subsyndromes. This study might contribute to a clearer understanding of the
      neuropsychiatric symptoms in AD.

PMID- 20130407
TI  - Clinical relevance of IgG antibodies against food antigens in Crohn's disease: a
      double-blind cross-over diet intervention study.
AB  - BACKGROUND: Environmental factors are thought to play an important role in the
      development of Crohn's disease (CD). Immune responses against auto-antigens or
      food antigens may be a reason for the perpetuation of inflammation. METHODS: In a
      pilot study, 79 CD patients and 20 healthy controls were examined for food
      immunoglobulin G (IgG). Thereafter, the clinical relevance of these food IgG
      antibodies was assessed in a double-blind cross-over study with 40 patients.
      Based on the IgG antibodies, a nutritional intervention was planned. The
      interferon (IFN)gamma secretion of T cells was measured. Eosinophil-derived
      neurotoxin was quantified in stool. RESULTS: The pilot study resulted in a
      significant difference of IgG antibodies in serum between CD patients and healthy
      controls. In 84 and 83% of the patients, respectively, IgG antibodies against
      processed cheese and yeast were detected. The daily stool frequency significantly
      decreased by 11% during a specific diet compared with a sham diet. Abdominal pain
      reduced and general well-being improved. IFNgamma secretion of T cells increased.
      No difference for eosinophil-derived neurotoxin in stool was detected.
      CONCLUSION: A nutritional intervention based on circulating IgG antibodies
      against food antigens showed effects with respect to stool frequency. The
      mechanisms by which IgG antibodies might contribute to disease activity remain to
      be elucidated.

PMID- 20130408
TI  - Bioavailability of buprenorphine from crushed and whole buprenorphine (subutex)
      tablets.
AB  - BACKGROUND: Buprenorphine (Subutex) is the most abused opioid in Finland. In
      order to curb the abuse potential of this drug, many treatment centers and
      prisons crush Subutex tablets before administering them to patients. To date,
      there are no published studies comparing the efficacy and bioavailability of
      crushed and whole Subutex tablets. METHODS: A total of 16 opioid-dependent
      patients stabilized on 24 mg of buprenorphine were enrolled in a double-blind,
      double-dummy, randomized cross-over study comparing crushed and whole
      buprenorphine tablets on a range of pharmacokinetic and pharmacodynamic
      variables. Buprenorphine tablets (either crushed or whole) and placebo tablets
      (either crushed or whole) were administered to subjects simultaneously.
      Buprenorphine and norbuprenorphine serum levels were measured at 30, 60, 90, 120,
      180, 240 and 360 min, as well as 24 h, after tablet administration. After 1 week,
      the experiment was repeated in a cross-over design so that, by the end of the
      study, each patient had received the active drug (buprenorphine) as both crushed
      and whole tablets. RESULTS: Pharmacokinetic parameters (mean serum levels,
      C(max), T(max), AUC) of buprenorphine or norbuprenorphine did not differ
      significantly between crushed and whole tablets, although serum levels were
      slightly higher after administration of the crushed tablets. There were also no
      significant differences in dissolution/absorption time, withdrawal signs or
      opiate craving. CONCLUSION: We conclude that crushing Subutex tablets does not
      significantly alter serum buprenorphine or norbuprenorphine levels or the drug's
      clinical effect. Our results indicate that crushing Subutex tablets may be used
      as an alternative method to counter the risk of buprenorphine diversion.

PMID- 20130410
TI  - Multiple sclerosis and the accumulation of iron in the Basal Ganglia:
      quantitative assessment of brain iron using MRI t(2) relaxometry.
AB  - The aim of this work was to quantify the accumulation of iron in the basal
      ganglia in multiple sclerosis (MS) patients and in a control group, and to
      investigate the relationship between iron accumulation and other parameters
      assessed in MS, i.e. lesion load (LL) and brain parenchymal fraction (BPF).
      Magnetic resonance imaging T(2) relaxometry was used for the measurement. 970
      patients with clinically definite MS and 117 controls were examined. Patients
      were divided into three subgroups according to LL and BPF. This work provides
      quantitative evidence of increased iron accumulation in the basal ganglia in MS
      patients in comparison to healthy controls. We also found that in the subgroup
      with small LL value, iron accumulation is higher than in the subgroup with large
      LL value. The hypothesis of a neurodegenerative component of MS is supported by
      the changes in iron content in the brain.

PMID- 20130409
TI  - Non-injection drug use patterns and history of injection among street youth.
AB  - AIMS: Efforts to prevent youth from initiating injection drug use require an
      understanding of the drug use patterns that predispose to injecting. Here we
      identify such patterns and describe the circumstances of first injection among
      street youth. METHODS: From October 2005 to November 2007, data were collected
      for the At Risk Youth Study, a prospective cohort of 560 street-recruited youth
      aged 14-26 in Vancouver, Canada. Non-injection drug use behaviors were compared
      between those with and without a history of injection through multiple logistic
      regression. The circumstances of first injection were also examined in gender
      stratified analyses. RESULTS: Youth who had previously injected were more likely
      to have engaged in non-injection use of heroin or of crystal methamphetamine.
      Daily users of marijuana were less likely to have injected. Among prior
      injectors, the median age of first injection was lower among females. Females
      were also more likely to have had a sexual partner present at first injection and
      to have become a regular injector within one week of initiation. CONCLUSION:
      Preventing transition to injection among street youth may require special
      attention to predisposing drug use patterns and should acknowledge gender
      differences in the circumstances of first injection.

PMID- 20130411
TI  - Peroxisome proliferator-activated receptor-gamma and its coactivator-1alpha gene
      polymorphisms in Korean women with polycystic ovary syndrome.
AB  - BACKGROUND/AIMS: To investigate whether the peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) Pro12Ala and the PPAR-gamma coactivator-1alpha (PGC
      1alpha) Gly482Ser polymorphisms were associated with polycystic ovary syndrome
      (PCOS). METHODS: Genetic analyses of the PPAR-gamma Pro12Ala and the PGC-1alpha
      Gly482Ser polymorphisms were performed in 184 patients with PCOS and 256
      controls. Hormone levels, biochemical and clinical features were analyzed
      according to these polymorphisms. RESULTS: Neither the PPAR-gammaPro12Ala nor the
      PGC-1alpha Gly482Ser polymorphism showed significant differences in genotypic
      distribution between women with PCOS and controls. In PCOS patients, women with
      the non-Pro/Pro genotypes of the PPAR-gamma Pro12Ala polymorphism showed
      statistically significantly higher HDL levels than those with the Pro/Pro
      genotype (p = 0.002). PCOS patients who had the Ser/Ser genotype of the PGC
      1alpha Gly482Ser polymorphism had significantly higher levels of postprandial 2
      hour insulin than those with the Gly/Ser genotype (p = 0.045). CONCLUSIONS:
      Neither the PPAR-gammaPro12Ala nor the PGC-1alpha Gly482Ser polymorphism were
      supposed to be susceptible genes in PCOS. However, in PCOS patients, the PPAR
      gammaPro12Ala and the PGC-1alpha Gly482Ser polymorphism may modulate the
      concentrations of serum HDL levels and postprandial 2-hour insulin level,
      respectively.

PMID- 20130412
TI  - First case of angioleiomyoma originating from the ovary of an adult woman.

PMID- 20130413
TI  - Constitutive and tumor necrosis factor-alpha-stimulated activation of nuclear
      factor-kappaB in immortalized endometriotic cells and their suppression by
      trichostatin A.
AB  - OBJECTIVE(S): To determine whether nuclear factor-kappaB (NF-kappaB) is
      constitutively and tumor necrosis factor (TNF)-dependently activated in
      endometriotic cells, whether trichostatin A (TSA) can suppress NF-kappaB
      activation and suppress TRAF2/6 and TAK1, and whether TSA and caffeic acid phenyl
      ester can suppress constitutive and H(2)O(2)-stimulated proliferation of
      endometriotic cells. METHODS: Two endometriotic cell lines and an endometrial
      stromal cell line were used as an in vitro model. Electrophoretic mobility shift
      analysis was used to determine NF-kappaB activation and possible suppression by
      TSA. Western blot analysis was used to determine whether TSA suppresses
      phosphorylation of IkappaBalpha, phosphorylation of p65 in the cytoplasm and
      nuclear translocation, and the expression of TRAF2/6 and TAK1. RESULTS: NF-kappaB
      was constitutively activated in endometriotic cells, but only minimally in
      endometrial cells. TNFalpha stimulation activated NF-kappaB through induction of
      IkappaB phosphorylation, but the activation can be suppressed by TSA. TSA also
      attenuated constitutive and TNF-dependent p65 phosphorylation and nuclear
      translocation in endometriotic cells. TRAF2, TRAF6 and TAK1 were constitutively
      activated and were unaffected by TSA treatment. CONCLUSIONS: NF-kappaB activation
      may play a critical role in the pathogenesis in endometriosis. Targeting NF
      kappaB with histone deacetylase inhibitors or other compounds might hold promise
      as novel therapeutics for endometriosis.

PMID- 20130414
TI  - Molecular and epidemiological characteristics of norovirus associated with
      community-based sporadic gastroenteritis incidents and norovirus outbreaks in
      Victoria, Australia, 2002-2007.
AB  - OBJECTIVES: The molecular and epidemiological features of community-based
      norovirus-associated sporadic gastroenteritis incidents (NASGIs) are poorly
      understood. This study examined these features and compared the findings with
      studies of community-based and institutional norovirus-associated gastroenteritis
      outbreaks (NAGOs). METHODS: Fecal specimens from NASGIs and NAGOs that occurred
      in Victoria, Australia (2002-2007) were tested for norovirus by reverse
      transcription-polymerase chain reaction methodology. Norovirus genotype was
      determined by nucleotide sequence analysis. RESULTS: 106 community-based NASGIs,
      116 community-based NAGOs and 902 institutional NAGOs were identified. The mean
      age and gender ratio of individuals associated with community-based NASGIs and
      community-based NAGOs were similar but differed from that found for institutional
      NAGOs. Although GII.4 was the predominant genotype associated with all three
      incident types, the mix of genotypes was similar for community-based NASGIs and
      community-based NAGOs but that for institutional NAGOs was different. All three
      incident types had a similar seasonal periodicity due to the pronounced seasonal
      periodicity of GII.4 incidents. CONCLUSIONS: The molecular and epidemiological
      features of noroviruses associated with community-based NASGIs and community
      based NAGOs are similar but are different from those found for institutional
      NAGOs.

PMID- 20130415
TI  - Appearance of HbeAg in an occult persistent hepatitis B virus infection.
AB  - Occult hepatitis B virus infection (OBI) is characterized by the presence of
      ongoing viral replication with very low levels of viremia (<200 IU/ml), and
      negativity for HBsAg, while the so-called 'false' OBI with higher levels of HBV
      DNA that are negative for HBsAg are usually due to the occurrence of mutations of
      the HBsAg sequence that may alter the recognition by some immunoassays. We
      describe here a case of occult HBV infection that combines both aspects. A male
      patient with severe systemic diseases, positive for anti-HBc and anti-HBs and
      negative for all other HBV markers, including HBsAg, since at least 4 years,
      showed a positivity for HBeAg at a follow-up control in November 2008; HBV-DNA
      testing by real-time PCR evidenced very low levels of viremia (<40 IU/ml), direct
      sequencing of the surface antigen-coding and Pol/RT coding regions allowed the
      identification of genotype D, serotype adw2, one immune escape mutation (G145R)
      and no drug resistance mutations. The positivity for HBeAg could be attributed to
      a superinfection in a naturally immune subject or to reactivation of a latent
      infection; the mutated virus had a reduced fitness and was therefore able to
      replicate only at low levels, resulting in a mild form of occult HBV infection.

PMID- 20130416
TI  - Association between stroke severity and fall risk among stroke patients.
AB  - BACKGROUND: Falls are common after stroke. Simple, clinically practical tools are
      needed to easily identify patients with stroke who are at risk of falls. The
      objective of this study was to identify the factors associated with increased
      fall risk in a poststroke population. METHODS: We assessed factors associated
      with fall risk among poststroke patients. Fall risk was determined through a
      history of falls, physical examination, observations of transfers, gait, balance,
      strength, range of motion, and use of assistive devices. Stroke severity was
      evaluated using the NIH Stroke Scale (NIHSS); mild or moderate-severe stroke was
      defined as a NIHSS score of <4 or > or = 4, respectively. RESULTS: Among 52
      poststroke patients, 26 (50%) were considered at risk of falls. Patients at risk
      of falls compared with those without fall risk were more likely to have greater
      stroke severity, decreased functional status, and to be more dependent in
      activities of daily living. Increased stroke severity was independently
      associated with higher fall risk (NIHSS > or = 4: OR = 5.73; 95% CI: 1.645
      19.94). CONCLUSION: Poststroke patients at risk of falls can be identified by an
      NIHSS score of > or = 4. Clinicians should screen patients for fall risk so that
      fall prevention strategies can be instituted.

PMID- 20130417
TI  - A prospective study of SCA3 gait ataxia described through a Markovian method.
AB  - BACKGROUND: Studies on the natural history of rare, chronic diseases like
      spinocerebellar ataxia 3 (SCA3) are hard to be done, since patients enter the
      study with variable disease durations and are followed up at irregular intervals.
      AIMS: Our purpose was to use all the available data to describe the progression
      of gait ataxia in a long-term cohort of patients with SCA3 through a markovian
      method. MATERIALS AND METHODS: SCA3 patients were recruited between 1998 and 2005
      and were invited to annual neurological follow-ups until 2007. Gait ataxia was
      described through a mean score graph and a mean trajectory graph. RESULTS: We
      followed up 105 patients; at baseline, the mean age and disease duration were,
      40.5 (SD = 12.6) and 7.7 (SD = 5.8) years, respectively. The mean time to reach
      stages 1, 2, 3 and 4 of gait ataxia were 3, 5.4, 10.8 and 19.4 years of disease
      duration. The mean score graph was unsmooth, showing several unlikely ups and
      downs. The mean trajectory graph produced a continuous curve. CONCLUSION: The
      markovian method described the natural history of gait ataxia without any a
      posteriori adjustment of data and allowed statistical comparisons between
      subgroups. This method will be useful in future clinical trials in this and in
      other chronic degenerative diseases.

PMID- 20130418
TI  - The incidence of myasthenia gravis: a systematic literature review.
AB  - BACKGROUND: A systematic review of literature published between 1980 and 2007, on
      the incidence of myasthenia gravis, was undertaken. METHODS: All relevant papers
      found through searches of Medline, Embase and Science Direct were critically
      appraised and an assessment was made of the reliability of the reported incidence
      data. RESULTS: Thirty-one studies were included in the review, the majority of
      which investigated populations in Europe. The incidence rates reported were
      between 3.0 and 30.0/1,000,000/year. However, it is thought that the rates at the
      upper end of this range, reported by the prospective studies, provided the most
      accurate estimates. Overall, incidence rates have increased over time owing to a
      greater awareness of the disease and improved methods of diagnosis. CONCLUSIONS:
      The most accurate estimate of incidence of myasthenia gravis was around 30/
      1,000,000/year. The incidence in children and adolescents aged 0-19 years was
      found to be between 1.0 and 5.0/ 1,000,000/year. The rates presented in this
      review are likely to be an underestimate of the true incidence rates, as mild
      cases will have been missed and cases in the elderly will have been misdiagnosed.

PMID- 20130419
TI  - Incidence of spinal cord injury worldwide: a systematic review.
AB  - BACKGROUND: Incidence studies of spinal cord injury (SCI) are important for
      health-care planning and epidemiological research. This review gives a
      quantitative update on SCI epidemiology worldwide through a statistical
      evaluation of incidence rates. METHODS: A systematic review was conducted. For
      each study, the crude rate ratio was calculated and, when possible, age- and
      gender-adjusted incidence rate ratios with 95% CI were determined by direct
      adjustment or using Poisson regression. RESULTS: Thirteen studies were included.
      Annual crude incidence rates in traumatic SCI varied from 12.1 per million in The
      Netherlands to 57.8 per million in Portugal. Compared to the Portuguese reference
      study, incidence rates showed a 3-fold variation, with the highest rates in
      Canada and Portugal. Most traumatic SCI studies showed a bimodal age
      distribution. The first peak was found in young adults between 15 and 29 years
      and a second peak in older adults (mostly > or = 65 years). Motor vehicle
      accidents and falls were the most prevalent causes of injury accounting for
      nearly equal percentages. In contrast, another age pattern in non-traumatic SCI
      reflected steadily increasing incidence with advancing age. CONCLUSIONS: The
      results show significant variation in SCI incidence with changing epidemiological
      patterns. A trend towards increased incidence in the elderly was observed, likely
      due to falls and non-traumatic injury.

PMID- 20130420
TI  - Spinal cord injury worldwide.

PMID- 20130421
TI  - VEGF-targeted short hairpin RNA inhibits intraperitoneal ovarian cancer growth in
      nude mice.
AB  - OBJECTIVE: In this study, we inhibited the expression of VEGF by short hairpin
      RNA (shRNA) in SKOV3 ovarian cancer cells in vitro and in vivo to explore the
      antitumor efficacy of shRNA in ovarian cancer cells. METHODS: ShRNA targeting
      VEGF was cloned into pGenesil-2 plasmid vector and then transfected into SKOV3
      ovarian cancer cells using liposome. Silencing of VEGF expression was measured by
      RT-PCR and ELISA assays. Furthermore, the growth inhibition capacity of shRNA on
      SKOV3 intraperitoneal ovarian carcinomatosis was tested in nude mice. Tumor
      weight was measured. Microvessel density, number of apoptotic cells and
      proliferation index in tumor tissues were assessed by CD31, TUNEL and PCNA
      immunostaining. RESULTS: shRNA targeting VEGF significantly silenced VEGF
      expression in SKOV3 ovarian cancer cells, confirmed by RT-PCR and ELISA assays (p
      < 0.05). In vivo, the shRNA reduced tumor weight by approximately 60.3% compared
      with control groups (p < 0.05), accompanied with angiogenesis inhibition (p <
      0.01) and apoptosis induction (p < 0.01). CONCLUSION: Our data indicated that
      shRNA-mediated silencing of VEGF might be a promising therapeutic strategy
      against ovarian cancer by reducing angiogenesis and inducing apoptosis.

PMID- 20130422
TI  - Chemotherapy resistance as a predictor of progression-free survival in ovarian
      cancer patients treated with neoadjuvant chemotherapy and surgical cytoreduction
      followed by intraperitoneal chemotherapy: a Southwest Oncology Group Study.
AB  - PURPOSE: In vitro testing of the activity of chemotherapeutic agents has been
      suggested as 1 method to optimally select drugs for patients with ovarian cancer.
      There are limited prospectively obtained data examining the clinical utility of
      this approach. We sought to obtain a preliminary assessment of this strategy in a
      trial that examined the administration of neoadjuvant chemotherapy followed by
      surgical cytoreduction and intraperitoneal chemotherapy in women with advanced
      ovarian cancer. METHODS: Women with stage III/IV epithelial ovarian carcinoma
      that presented with large-volume disease were treated with neoadjuvant
      intravenous paclitaxel and carboplatin for three 21-day cycles followed by
      cytoreductive surgery. If optimally debulked, patients received intravenous
      paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel for six 28
      day cycles. Tumor cloning assay results (Oncotech) were correlated with
      progression-free survival. RESULTS: Sixty-two patients (58 eligible) were
      registered from March 2001 to February 2006. Thirty-six eligible patients had
      interval debulking and 26 received postcytoreduction chemotherapy. Twenty-two
      patients had tumor cloning assay results available. The clinical features of this
      population were similar to those of the larger group of women who entered this
      study. There was no difference in progression-free survival between patients
      whose cancers were defined as 'resistant' or 'nonresistant' to either platinum or
      paclitaxel. CONCLUSIONS: While the small patient numbers in this trial do not
      permit definitive conclusions, these data fail to provide support for the
      argument that prospectively obtained in vitro data regarding platinum or
      paclitaxel resistance will be highly predictive of clinical outcome in advanced
      ovarian cancer.

PMID- 20130423
TI  - EGFR signaling and drug discovery.
AB  - Dysregulation of human epidermal growth factor receptor (ErbB/HER) pathways by
      over-expression or constitutive activation can promote tumor processes including
      angiogenesis and metastasis and is associated with poor prognosis in many human
      malignancies. In addition to cancer, ErbB signaling has also been implicated in
      cardiovascular and neurodegenerative diseases. Conversely, inhibition of ErbB
      pathways with targeted agents, such as monoclonal antibodies (MoAbs) or tyrosine
      kinase inhibitors (TKIs), blocks cell cycle progression, inhibits the production
      of pro-angiogenic factors and induces apoptosis in numerous in vitro and
      xenograft models. Accordingly, the ErbB receptor family with their most prominent
      members EGFR and HER-2 represents validated targets for anti-cancer therapy, and
      anti-ErbB MoAbs (cetuximab, panitumumab, and trastuzumab) and TKIs (gefitinib,
      erlotinib, and lapatinib) have now been approved for the treatment of advanced
      colorectal cancer, squamous cell carcinoma of the head and neck, advanced non
      small-cell lung cancer, as well as pancreatic and breast cancer. Although results
      have been encouraging, more work remains to be done.

PMID- 20130425
TI  - Prognostic applications of gene expression signatures in breast cancer.
AB  - Analysis by DNA microarrays has led to the identification of molecular subtypes
      of breast carcinomas that show a distinct expression profile. Several studies
      have demonstrated that this 'intrinsic subtype' classification has a strong
      prognostic value. In addition, gene expression profiling techniques have been
      used to identify gene signatures that could be associated with the outcome of
      breast cancer patients. Several different genomic tests have been shown to better
      define the prognosis of early-stage breast cancer patients as compared with
      conventional clinical and pathological characteristics of the tumors, and some
      assays are already commercially available. However, it must be emphasized that
      the prognostic power of these genetic classifiers has not been confirmed yet in
      prospective trials. Genetic signatures that might predict the activity of
      specific chemotherapy agents have also been developed by using gene expression
      profiling techniques. The same approach has been used to identify gene signatures
      associated with the activation of oncogenic pathways that might represent targets
      for molecular therapy of breast cancer. By using these approaches, gene
      expression techniques might significantly improve our ability to predict the risk
      of recurrence and to tailor the treatment for each individual breast cancer
      patient.

PMID- 20130426
TI  - Adjuvant endocrine treatment in premenopausal early breast cancer.
AB  - The impact of endocrine therapies in the adjuvant treatment of premenopausal
      patients with early breast cancer is well established. However, the right
      combination and duration of endocrine manipulations currently available
      (luteinizing hormone-releasing hormone analogs and tamoxifen) remain unclear.
      Moreover, the role of chemotherapy in addition to endocrine therapies is not
      clearly defined. The most recent Early Breast Cancer Trialists' Collaborative
      Group overview has confirmed the efficacy of five years of tamoxifen in reducing
      the annual recurrence rate and the annual breast cancer death rate by 41 and 34%,
      respectively, in an estrogen receptor-positive population. These results are
      largely irrespective of age, use of chemotherapy or other tumor features.
      Moreover, the expert panel of the St. Gallen Conference accepted both tamoxifen
      or tamoxifen plus ovarian suppression as standard endocrine therapy for
      premenopausal breast cancer patients with endocrine-responsive disease. The use
      of ovarian suppression or ablation also significantly reduced the risk of breast
      cancer-related death, mainly in the absence of other systemic therapies.
      Chemotherapy is widely used in this population; however, its role in endocrine
      positive premenopausal women with hormone-positive disease treated with optimal
      endocrine therapy remains unclear.

PMID- 20130427
TI  - Adjuvant chemotherapy for the treatment of HER2-positive early breast cancer.
AB  - HER2-positive breast cancer is characterized by high chemosensitivity.
      Anthracycline-based chemotherapy is recognized as a very effective adjuvant
      treatment in HER2-positive disease. One of the possible explanations is the co
      amplification of TOPO II-alpha and HER2. However, recent data seem to demonstrate
      that HER2 and TOPO II-alpha seem to be less predictive of anthracycline-based
      chemotherapy efficacy than chromosome 17 polysomy. Chromosome 17 polysomy is
      present in 21-40% of breast cancer and for this reason benefit of anthracycline
      based chemotherapy seems to be not restricted only to HER2-positive disease.
      Trastuzumab added to chemotherapy administered for one year is associated with
      improvement in disease-free survival and sometimes in overall survival compared
      to chemotherapy alone. Efficacy of trastuzumab in the adjuvant setting seems to
      be increased if administered concomitantly with chemotherapy instead of
      sequentially. However, the interpretation of longer follow-up results is
      difficult because of a large crossover from the control arm to trastuzumab.

PMID- 20130428
TI  - Which patients with estrogen receptor-positive early breast cancer should be
      treated with adjuvant chemotherapy?
AB  - Estrogen receptor expression in breast cancer cells represents an important
      predictive and prognostic factor. The estrogen receptor is a target for endocrine
      therapy, which avoids chemotherapy especially in highly hormone-sensitive early
      breast cancer. Paradoxically, recent data from several clinical trials and meta
      analyses have demonstrated the superiority of adjuvant chemotherapy independently
      of age, estrogen receptor and nodal status. For this reason, new tools are needed
      to better define the intrinsic characteristics of breast cancers and to establish
      the role of cytotoxic treatment for those tumors with potentially good outcome,
      such as hormone-sensitive early breast cancer.

PMID- 20130429
TI  - Molecular mechanism and clinical implications of endocrine therapy resistance in
      breast cancer.
AB  - Endocrine therapy, the first targeted therapy in oncology, is the most successful
      systemic therapy in the management of estrogen receptor (ER)-positive breast
      cancer. Approximately 50% of patients with advanced disease do not respond to
      first-line treatment with tamoxifen, and many women who receive tamoxifen as
      adjuvant therapy experience tumor relapse and die from their disease. Aromatase
      inhibitors are proving superior to tamoxifen, at least in certain patient
      subsets. However, the response rate to these compounds is only slightly higher
      than that to tamoxifen in patients with advanced breast cancer, and both de novo
      or acquired resistance also occur, limiting the efficacy of the treatment.
      Advanced studies of ER biology have highlighted the role of an intimate cross
      talk between the ER and HER2/growth factor signaling pathways as a fundamental
      contributor to the development of resistance to hormone therapies. The aim of
      this review article is to summarize the current knowledge on mechanisms of
      resistance of breast cancer cells to endocrine therapies due to the cross talk
      between the ER and growth factor signaling pathways, and to explore newly
      available therapeutic strategies that could prolong duration of response and
      circumvent endocrine-resistant tumor growth.

PMID- 20130430
TI  - Perspectives in adjuvant therapy of gastric cancer.
AB  - Although the incidence of gastric cancer has been declining in Western countries,
      it is still a major health problem and a leading cause of cancer mortality.
      Surgery is the mainstay of treatment for gastric adenocarcinoma. However, even
      among patients undergoing gastrectomy with curative intent, 5-year survival rates
      are disappointing due to locoregional relapse and distant metastases. This
      emphasizes the importance of multidisciplinary management of patients with
      gastric cancer. In contrast to the preoperative approach, several phase III
      trials have been carried out in the adjuvant setting, but postoperative
      chemotherapy has not proven to be superior to surgery alone. Therefore, at
      present the routine use of adjuvant therapy should be regarded as an
      investigational approach. Improved clinical trial designs with standardized
      surgical techniques and the incorporation of newer active drugs are needed.

PMID- 20130431
TI  - Treatment of hepatocellular carcinoma.
AB  - As a result of progresses in surveillance programs and improvements in diagnosis,
      an increased number of hepatocellular carcinomas are diagnosed in early stage,
      when effective treatment options are available. Surgical resection, liver
      transplantation and radiofrequency ablation are considered potentially curative
      treatments and may be successfully applied when the disease is limited. In
      intermediate and advanced stages only palliative therapies can be employed and
      chemoembolization and the oral dual inhibitor sorafenib are considered the
      treatments of choice. Future directions will explore the role of sorafenib in the
      adjuvant setting, the addition of sorafenib to chemoembolization procedures and
      the combination of sorafenib with chemotherapeutic agents or other biological
      drugs in advanced stages of disease.

PMID- 20130432
TI  - Adjuvant therapy in colon cancer.
AB  - Colon cancer is the second leading cause of cancer death worldwide. Approximately
      three quarters of patients are diagnosed with disease limited to the bowel wall
      or surrounding lymph nodes. Over the past decade, significant progress has been
      made in the treatment of localized colon cancer. The use of adjuvant chemotherapy
      has improved prognosis in stage III disease, but much work remains to be done in
      optimizing adjuvant treatment. The FOLFOX4 regimen is now considered standard
      treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5
      FU) have not proven to be more effective than 5-FU/folinic acid. In stage II, the
      value of post-operative treatment remains controversial, but the identification
      of histopathological and molecular prognostic factors would allow selection of
      patients who can benefit from adjuvant treatment. The inclusion of molecular
      targeted agents in combination regimens with cytotoxins, which have already
      proven effective in advanced disease, is the main field of development in the
      most recent protocols of adjuvant therapy.

PMID- 20130433
TI  - The long and winding road to useful predictive factors for anti-EGFR therapy in
      metastatic colorectal carcinoma: the KRAS/BRAF pathway.
AB  - Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have
      improved outcomes for patients with metastatic colorectal carcinoma. Among
      patients not carrying activating mutations in the KRAS gene, only a limited
      number will experience tumor response to these therapeutic agents. The role of
      BRAF mutations in determining resistance to this treatment is emerging through
      preclinical and clinical studies. Standardization and validation of laboratory
      mutation analysis is needed to allow an optimal use of anti-EGFR therapies in the
      management of colorectal carcinoma. Clinical single-arm and randomized studies
      were conducted both in first-line and refractory settings to evaluate the
      correlation of KRAS mutational status and efficacy of cetuximab and panitumumab.
      The main trials on first-line regiments are CRYSTAL, which is looking at FOLFIRI
      (folinic acid, fluorouracil, irinotecan) + cetuximab, and OPUS, which is
      evaluating FOLFOX (folinic acid, fluorouracil, oxaliplatin) + cetuximab. The
      results of these trials have induced the European Medicines Agency to apply
      restrictions to its approval of cetuximab and panitumumab for use in metastatic
      colorectal cancer patients with wild-type KRAS tumors. However, the absence of
      KRAS mutations is not sufficient to assure clinical response to cetuximab and
      panitumumab. We need to discover further molecular biomarkers of impairment in
      this or other signaling pathways to identify responders more specifically.
      Preclinical rationale is available for combined therapies, which simultaneously
      target EGFR and the RAS/RAF/MAPK signaling pathways for metastatic colorectal
      cancer.

PMID- 20130434
TI  - The dark side of the moon: the PI3K/PTEN/AKT pathway in colorectal carcinoma.
AB  - Wild-type KRAS status is required but not sufficient to confer sensitivity to
      anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in
      colorectal cancer patients. As a consequence, one of the major challenges is to
      identify, in non-mutant KRAS patients, other markers that can predict lack of
      response to this therapy. Small series have investigated the clinical effect of
      PIK3CA mutations on resistance to anti-EGFR mAbs and discrepant results have been
      observed. Furthermore, PTEN loss in metastases may be predictive of resistance to
      anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical
      application. The introduction of modulators of the PI3K/AKT/mTOR pathway as
      potential targeted anticancer drugs is encouraging, but this attractive therapy
      option is still at an early stage of development.

PMID- 20130435
TI  - MicroRNAs as a new potential therapeutic opportunity in gastrointestinal cancer.
AB  - MicroRNAs (miRNAs) comprise an abundant class of small non-coding RNAs that act
      as important post-transcriptional regulators of gene expression. Accumulating
      evidence shows that aberrantly expressed miRNAs play important roles in human
      cancers and underscores them as potential targets for therapeutic intervention.
      Basic research has provided strong evidence about the role of miRNA as oncogenes
      and as tumor suppressor genes in cancer. In accord with this finding, miRNA-based
      cancer therapy is a very interesting field of investigation that offers the
      appeal of targeting multiple gene networks controlled by a single, aberrantly
      expressed miRNA. A new door in cancer research is opening and it may lead to the
      modulation of miRNAs.

PMID- 20130436
TI  - Biological prognostic and predictive factors in lung cancer.
AB  - The inclusion of new drugs in clinical research and practice has allowed
      improvements in several outcomes of advanced non-small-cell lung cancer (NSCLC).
      Among these drugs, very interesting results have been obtained from pemetrexed
      and new targeted agents, including the inhibitors of epidermal growth factor
      receptor (EGFR) such as gefitinib, erlotinib and cetuximab. Unfortunately, these
      new drugs when investigated for the treatment of small-cell lung cancer (SCLC)
      reported negative results. The results of these investigations seem to be related
      to specific factors that could indicate which patients could benefit from each
      specific therapy. Therefore, several clinical and biological factors might find
      use as prognostic or predictive markers. A prognostic factor provides information
      on outcome, independent of the therapy that is used. In contrast, a predictive
      factor provides information on outcome with regard to a specific therapy. Some
      factors, such as EGFR mutations, are both prognostic and predictive. In the
      present paper, we review data related to thymidylate synthase, EGFR and K-ras
      mutations, the most important biologic prognostic and/or predictive factors
      related to pemetrexed, gefitinib, erlotinib and cetuximab therapy in the
      treatment of advanced NSCLC and in SCLC patients.

PMID- 20130437
TI  - Evolution of therapy decision-making process for advanced non-small cell lung
      cancer.
AB  - Advanced non-small cell lung cancer remains a lethal disease with poor prognosis.
      In the last decades results of systemic chemotherapy have reached a disappointing
      plateau without significant differences between the most widely employed third
      generation regimens. Recent scientific evidence has shed new light on the
      management of advanced non-small cell lung cancer, especially for the important
      role of histological definition in therapy-planning process. The results of new
      biologic agents are also reported as are the promising data on pharmacogenomic
      guided treatment.

PMID- 20130438
TI  - New agents in advanced non-small-cell lung cancer treatment.
AB  - Lung cancer is the leading cause of cancer deaths worldwide. Novel targeted
      therapies based on specific molecular and biological characteristics of lung
      cancer have emerged as a new treatment paradigm. The current globally accepted
      standard of treatment for advanced non-small-cell lung cancer (NSCLC) is platinum
      based combination therapy. Recently, several ongoing phase I and II trials with
      new drugs in NSCLC have been registered, such as sorafenib, sunitinib, mTOR
      inhibitors and ASA404. The optimal use of new agents is more likely in
      combination with standard cytotoxic or other targeted agents. Further
      investigations into adverse events with targeted therapy are urgently needed as
      these impact an increasing number of patients.

PMID- 20130439
TI  - Third-line therapy for advanced non-small-cell lung cancer patients: a feasible
      therapeutic option?
AB  - Two decades ago best supportive care was considered a valid therapeutic option
      for advanced non-small cell lung cancer (NSCLC) patients until the evidence
      derived from meta-analysis showed symptom improvement and a survival advantage
      from systemic chemotherapy. A further advantage was reported when docetaxel and
      pemetrexed were used as second-line treatment after failure of first-line
      platinum-based chemotherapy. Furthermore, the biologic therapies targeting the
      epidermal growth factor receptor - erlotinib and gefitinib - have modified the
      therapeutic approach to second- and third-line treatment of NSCLC patients. In
      fact, to date, erlotinib is the only drug to be licensed for third-line therapy
      worldwide. So, third-line represents a new frontier to be assessed in advanced
      NSCLC patients. Third-line therapy is very hard to define correctly as it is
      difficult to interpret the currently available evidence-based data. A better
      knowledge of cellular biology will certainly encourage clinical research and
      could allow oncologists to best select patients and treatments. Here we review
      the state of the art of third-line therapy in the treatment of NSCLC patients.

PMID- 20130440
TI  - Targeted therapy in the treatment of metastatic renal cell cancer.
AB  - The treatment of metastatic renal cell carcinoma (MRCC) has evolved from being
      predominantly cytokine-based to being grounded in the use of drugs targeting
      vascular endothelial growth factor, platelet-derived growth factor and mammalian
      target of rapamycin (mTOR) pathways. New agents including the small-molecule
      targeted inhibitors sunitinib, sorafenib and temsirolimus and the monoclonal
      antibody bevacizumab have shown anti-tumor efficacy and have become the standard
      of care for most patients. Sunitinib and temsirolimus have shown significant
      improvements in overall survival (OS), in the first-line setting, when compared
      with interferon. Sorafenib has demonstrated prolonged progression-free survival
      (PFS) in a phase III study in comparison with placebo in the second-line setting.
      More recently, two phase III studies have compared bevacizumab and interferon
      with interferon alone. Both studies showed a statistically significant
      improvement in PFS for the combination arm but no difference in OS. Everolimus
      showed prolonged PFS in the second/third-line setting. Pazopanib prolongs PFS in
      naive/cytokine refractory patients. Immunotherapy confers a small but significant
      OS advantage but only for the minority of patients with good prognostic features.
      The results of these trials and ongoing efforts to improve treatment of MRCC are
      the focus of this review.

PMID- 20130441
TI  - Applications of nanobiotechnology in ophthalmology--Part I.
AB  - Much progress has been achieved in the field of nanotechnology and its
      applications in ophthalmology. It is evident that drug delivery, gene therapy,
      implantable devices and regenerative medicine are some of the key areas of active
      research. To the best of our knowledge, there is limited review work on this
      subject area in the current literature. To assist the interested clinicians and
      scientists, this bipartite commentary will focus the discussion on emerging
      researches in nano-ophthalmology and other enabling technologies that soon may be
      available in the clinician's armamentarium to maintain and restore eye sight.
      This installment will focus on recent discoveries in drug delivery, gene therapy,
      imaging and visual prostheses; the second installment will discuss the impact of
      nanotechnology on artificial environment, cell-nanostructure interaction, other
      enabling nano-ophthalmic technologies, and safety and biocompatibility of
      nanostructures. We will take this opportunity to introduce some exciting nano
      ophthalmic applications under investigation in our laboratory. The
      accomplishments by the scientific community are tremendous and the future
      prospects are wide open.

PMID- 20130442
TI  - Electrophysiological retinal pigment epithelium changes observed with indocyanine
      green, trypan blue and triamcinolone.
AB  - BACKGROUND: Intravitreal application of indocyanine green (ICG), trypan blue (TB)
      or triamcinolone (TA) during vitreoretinal surgery has been associated with
      severe damage to the retinal pigment epithelium (RPE). However, the physiological
      background of these findings remains to be assessed. METHODS: In bovine RPE
      choroid preparations maintained in Ussing chambers, the effect of apical
      application of ICG, TA (filtered and not filtered) and TB at different
      concentrations was evaluated. The electrophysiological parameters
      (transepithelial potential, tissular resistance and short-circuit current) were
      continuously monitored. The experiments were conducted either in daylight or in
      dark-adapted conditions. RESULTS: After apical application of ICG and TA
      (purified and not purified), all bioelectrical parameters were affected in a dose
      dependent manner. No significant changes were observed when the preparations were
      exposed to daylight. No changes were observed with TB. CONCLUSIONS: The
      electrophysiological results of apical application may explain the toxic effects
      observed after intraoperative use of ICG and TA. In this RPE study, TB appears to
      be the safest visualization aid for vitreoretinal surgery.

PMID- 20130443
TI  - Tryptophan hydroxylase as novel target for the treatment of depressive disorders.
AB  - Serotonin (5-HT) is a monoamine implicated in a variety of physiological
      processes that functions either as a neurotransmitter or as a peripheral hormone.
      Pharmacological and genetic studies in humans and experimental animals have shown
      that 5-HT is important for the pathophysiology of depressive disorders. The 5-HT
      system is thus already a main target for the therapy of these diseases. The
      peripheral and cerebral biosynthesis of 5-HT is initiated by two distinct
      tryptophan hydroxylases: TPH1 and TPH2. This duality of the serotonergic system
      and the existence of a brain-specific TPH isoform provide a promising new target
      for pharmacological intervention with higher selectivity and specificity and,
      therefore, possibly with reduced side effects and increased efficiency. This
      paper summarizes the data which support TPH2 as novel drug target and discusses
      strategies for its pharmacological exploitation.

PMID- 20130444
TI  - Future prospects for luteinizing hormone-releasing hormone analogues in prostate
      cancer treatment.
AB  - Luteinizing hormone-releasing hormone (LHRH) analogues play a pivotal role in
      hormonal therapy regimens for the treatment of prostate cancer. Hormonal therapy
      has traditionally been used as a palliative treatment for patients with advanced
      disease, and international treatment guidelines do not recommend its use as a
      first-line therapy at earlier disease stages. However, there appears to be a gap
      between international guideline recommendations and actual clinical practice
      regarding the use of primary androgen deprivation therapy (PADT) for prostate
      cancer therapy. Despite limited evidence to date for the impact on clinical
      outcomes, the use of PADT in patients with localized or locally advanced prostate
      cancer has increased in many countries, most notably Japan. Clinical evidence is
      now accumulating to confirm the valuable role of PADT, both as monotherapy but
      particularly when used as part of a maximal androgen blockade regimen, on the
      long-term control of both localized and locally advanced disease, and importantly
      on survival outcomes in these patients.

PMID- 20130445
TI  - O-GlcNAc-selective-N-acetyl-beta-D-glucosaminidase activity and mRNA expression
      in muscle is related to glucosamine-induced insulin resistance.
AB  - Glucosamine (GlcN)-induced insulin resistance is associated with an increase in O
      linked-N-acetylglucosaminylated modified proteins (O-GlcNAcylated proteins). The
      role played by O-GlcNAc-selective-N-acetyl-beta-D-glucosaminidase (O-GlcNAcase),
      which removes O-N-acetyl-glucosamine residues from O-GlcNAcylated proteins, has
      not yet been demonstrated. We investigated whether GlcN-induced whole-body
      insulin resistance is related to tissue O-GlcNAcase activity and mRNA expression.
      GlcN (30 mumol/kg/min) or physiological saline (control) was intravenously
      infused into Sprague-Dawley rats for 2 h. After GlcN treatment, rats were
      subjected to the following: intravenous glucose tolerance test, insulin tolerance
      test or removal of the liver, muscle and pancreas. GlcN was found to provoke
      hyperglycemia compared to control (8.6 +/- 0.41 vs. 4.82 +/- 0.17 mM, p < 0.001).
      The insulin resistance index (HOMA-IR) increased (15.76 +/- 1.47 vs. 10.14 +/-
      1.41, p < 0.001) and the beta-cell function index (HOMA-beta) diminished (182.69
      +/- 22.37 vs. 592.01 +/- 103, p < 0.001). Liver glucose concentration was higher
      in the GlcN group than in the control group (0.37 +/- 0.04 vs. 0.24 +/- 0.038
      mmol/g dry weight, p < 0.001). Insulin release index (insulin/glucose) was less
      in the GlcN group than in the control (2.2 +/- 0.1 vs. 8 +/- 0.8 at 120 min, p <
      0.001). In the GlcN group, muscle O-GlcNAcase activity diminished (0.28 +/- 0.019
      vs. 0.36 +/- 0.018 nmol of p-nitrophenyl/mg protein/min, p < 0.001), and K(m)
      increased (1.51 +/- 0.11 vs. 1.12 +/- 0.1 mM, p < 0.001) compared to the control.
      In the GlcN group, O-GlcNAcase activity/mRNA expression was altered (0.6 +/- 0.07
      vs. 1 +/- 0.09 of control, p < 0.05). In conclusion, O-GlcNAcase activity is
      posttranslationally inhibited during GlcN-induced insulin resistance.

PMID- 20130446
TI  - The promise of novel androgen receptor antagonists.

PMID- 20130447
TI  - O(6)-methylguanine in DNA: bad penny?

PMID- 20130448
TI  - DNA double strand breaks: not all foci are created equal.

PMID- 20130449
TI  - Shifting focus.

PMID- 20130450
TI  - The anatomy and cell cycle evolution of DNA damage signaling and repair foci.

PMID- 20130451
TI  - SBE13 joins the family of Polo-like kinase 1 (Plk1) inhibitors.

PMID- 20130452
TI  - Cyclin D3-dependent kinases in lymphoma: redundancy and implications for therapy.

PMID- 20130453
TI  - Shifting gears and putting on the brakes: Female germ cells transition into
      meiosis.

PMID- 20130454
TI  - Cyclins D3 and E go hand in hand with Cdk4/6 in diffuse large B-cell lymphoma.

PMID- 20130456
TI  - New insights for the diagnosis and management of right ventricular failure, from
      molecular imaging to targeted right ventricular therapy.
AB  - PURPOSE OF REVIEW: Despite the recognition of a critical role of the right
      ventricle (RV) in many aspects of cardiovascular medicine, there has been
      surprisingly little interest in right ventricular-targeted imaging and
      therapeutic approaches. Compared with the left ventricle, the RV has a different
      embryologic origin, undergoes a dramatic change during the transition from the
      fetal to the adult circulation and normally operates in a low resistance or
      impedance arterial system. Here, we review new insights on the pathophysiology,
      assessment and management of right ventricular failure. RECENT FINDINGS: Our
      understanding of the mechanisms underlying right ventricular failure has
      improved. As in the left ventricle, decrease in alpha-myosin heavy chain and a
      switch towards glycolysis from fatty acid oxidation is observed in the stressed
      RV, but the key question remains unanswered: why is the RV so much more
      vulnerable to failure upon afterload increase compared with the left ventricle?
      In assessing the RV, it is becoming increasingly important to consider the RV and
      pulmonary artery as a unit. New therapies that could specifically target the RV,
      such as metabolic modulators and phosphodiesterase type 5 inhibitors, are now
      being considered. SUMMARY: A better understanding of the molecular mechanisms of
      right ventricular failure will lead to the development of new strategies for the
      diagnosis and management of right ventricular failure. Right ventricular-targeted
      therapies are needed in a number of diseases in which only the RV fails.

PMID- 20130457
TI  - Current world literature.

PMID- 20130460
TI  - Can teaching research methodology influence students' attitude toward science?
      Cohort study and nonrandomized trial in a single medical school.
AB  - BACKGROUND: Medical teaching aims to develop attitudes and behaviors underlying
      professional competence of future physicians. We investigated whether a mandatory
      course on scientific methodology in the second study year could affect students'
      attitudes toward science in medicine. METHOD: In a longitudinal study, students
      (n = 241) enrolling in 2001-2002 academic year at a single medical school were
      followed up until graduation in 2006-2007. Each year, they filled out a Likert
      type questionnaire of 18 statements evaluating attitude toward science. Direct
      influence of the course on students' attitudes was tested in a nonrandomized
      controlled trial with the 2006-2007 second year student cohort. RESULTS: Positive
      students' attitudes toward science increased during study years (mean [SD] score
      of the maximum score of 90): from 57.6 (6.0) in the first to 69.8 (10.4) in the
      sixth year. There was a significant trend of increase in attitudes with the years
      of study (cubic trend by polynomial contrasts analysis, P = 0.011). Attendance of
      a course on research methodology significantly increased positive attitudes
      (score, 67.0 [7.0] before and 70.8 [7.5] after course, P = 0.032 vs control
      group), regardless of grade point average. The intervention had an effect even
      when the influence of the initial attitude was accounted for (F1,140 = 9.25, P =
      0.003; analysis of covariance). The attitude changes after the course was
      greatest in students with low initial attitude scores (Spearman rinitial score,
      score difference, -0.44). CONCLUSIONS: Medical students have positive attitudes
      toward science and scientific method in medicine. Attendance of a course on
      research methodology had positive short-term effect on students' attitudes toward
      science. This positive effect should be maintained by vertical integration of the
      course in the medical curriculum.

PMID- 20130462
TI  - Lymph node status and depth of invasion in early gastric cancer staging: two
      sides of the same coin.

PMID- 20130464
TI  - Announcing the arrival of metabolic surgery for diabetes.

PMID- 20130465
TI  - Extremity soft tissue sarcoma in a series of patients treated at a single
      institution: local control directly impacts survival.
AB  - PURPOSE: To improve understanding of what is adequate in local treatment of
      extremity soft tissue sarcomas (ESTS), to maximize the ratio between local
      control, limb preservation and prognosis. PATIENT AND METHODS: Nine hundred
      ninety-seven consecutive patients affected by primary ESTS were reviewed. Size,
      depth, histotype and grade of the tumor, margin status (R0, R1, R2) of surgical
      resection, and adjuvant treatments were analyzed. Univariable and multivariable
      analysis were carried out. For the subgroup of R1 resection the presence/absence
      of the tumor at the inked surface and the presence/absence of an anatomic barrier
      were also considered. RESULTS: Five- and 10-year mortality estimates (95%
      confidence interval) were 0.29 (0.20-0.38) and 0.38 (0.28-0.49) in R1 cases, and
      0.16 (0.13-0.19) and 0.19 (0.16-0.23) in R0 cases (P = 0.0003). Size, grade,
      depth, and histologic subtype were also significant predictor of mortality.
      Significant determinants for local relapse were surgical margins, radiation
      therapy, and histologic subtype. In the subset of R1 resections trends towards a
      better local control for R1 negative cases and histology other than
      myxofibrosarcoma were identified. Significant determinants for distant metastases
      were size, grade and histologic subtype of the tumor but not surgical margins.
      CONCLUSIONS: Quality of surgical margins independently predicted local control
      and survival. The effect on survival was directly mediated by local recurrence to
      proximal sites invading the abdomen/thorax, and this may indeed be the main way
      by which quality of surgery directly impacts the final prognosis of ESTS
      patients.

PMID- 20130466
TI  - Hospitalization rates before and after adult-to-adult living donor or deceased
      donor liver transplantation.
AB  - OBJECTIVE: To compare rates of hospitalization before and after adult-to-adult
      living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT).
      SUMMARY BACKGROUND DATA: LDLT recipients have been reported to have lower
      mortality but a higher complication rate than DDLT recipients. The higher
      complication rate may be associated with greater consumption of inpatient
      hospital resources and a higher burden of disease for LDLT recipients. METHODS:
      Data from the 9-center Adult-to-Adult Living Donor Liver Transplantation
      retrospective cohort study were analyzed to determine pretransplant, transplant,
      and posttransplant hospitalizations among LDLT candidates (potential living donor
      was evaluated) who received LDLT or DDLT. Hospital days and admission rates for
      LDLT and DDLT patients were calculated per patient-year at risk, starting from
      the date of initial potential donor history and physical examination. Rates were
      compared using overdispersed Poisson regression models. RESULTS: Among 806
      candidates, 384 received LDLT and 215 received DDLT. In addition to the 599
      transplants, there were 1913 recipient hospitalizations (485 pretransplant; 1428
      posttransplant). Mean DDLT recipient pretransplant, transplant, and
      posttransplant lengths of stay were 5.8 +/- 6.3, 27.0 +/- 32.6, and 9.0 +/- 14.1
      days, respectively, and for LDLT were 4.1 +/- 3.7, 21.4 +/- 24.3, and 7.8 +/-
      11.4 days, respectively. Compared with DDLT, LDLT recipients had significantly
      lower adjusted pretransplant hospital day and admission rates, but significantly
      higher posttransplant rates. Significantly higher LDLT admission rates were
      observed for biliary tract morbidity throughout the second posttransplant year.
      Overall hospitalization rates starting from the point of potential donor
      evaluation were significantly higher for eventual recipients of LDLT.
      CONCLUSIONS: LDLT recipients, despite lower acuity of disease, have higher
      hospitalization requirements when compared with DDLT recipients. Continuing
      efforts are warranted to reduce the incidence of complications requiring post
      LDLT inpatient admission, with particular emphasis on biliary tract issues.

PMID- 20130467
TI  - Effect of artemisinin derivatives on apoptosis and cell cycle in prostate cancer
      cells.
AB  - Artemisinin is a plant-derived anti-malarial drug that has relatively low
      toxicity in humans and is activated by heme and/or intracellular iron leading to
      intracellular free radical formation. Interestingly, artemisinin has displayed
      anti-cancer activity, with artemisinin dimers being more potent than monomeric
      artemisinin. Intracellular iron uptake is regulated by the transferrin receptor
      (TfR), and the activity of artemisinin depends on the availability of iron. We
      examined the level of TfR in prostate cancer (PCa) tumor cells, synthesized two
      new artemisinin dimers, and evaluated the effect of dihydroartemisinin and
      artemisinin dimers, ON-2Py and 2Py, on proliferation and apoptosis in PCa cells.
      TfR was expressed in the majority of PCa bone and soft tissue metastases, all 24
      LuCaP PCa xenografts, and PCa cell lines. After treatment with
      dihydroartemisinin, ON-2Py, or 2Py all PCa cell lines displayed dose-dependent
      decrease in cell number. 2Py was most effective in decreasing cell number. An
      increase in apoptotic events and growth arrest was observed in the C4-2 and LNCaP
      cell lines. Growth arrest was observed in PC-3 cells, but no significant change
      was observed in DU 145 cells. Treatment with 2Py resulted in a loss of the anti
      apoptotic protein survivin in all four cell lines. 2Py treatment also decreased
      androgen receptor and prostate-specific antigen expression in C4-2 and LNCaP
      cells, with a concomitant loss of cell cycle regulatory proteins cyclin D1 and c
      Myc. This study shows the potential use of artemisinin derivatives as therapeutic
      candidates for PCa and warrants the initiation of preclinical studies.

PMID- 20130468
TI  - Physical activity reduces the risk of symptomatic gallstones: a prospective
      cohort study.
AB  - BACKGROUND AND AIMS: Physical activity may prevent gallstones formation by
      reducing bile stasis and plasma triglycerides and elevating high-density
      lipoprotein cholesterol levels. This prospective study investigated the
      relationship of physical activity and symptomatic gallstones in both sexes, using
      a questionnaire validated against physiological measurements. METHODS: A total of
      25 639 volunteers, aged 40-74 years, were recruited into the European Prospective
      Investigation of Cancer, Norfolk and completed a questionnaire recording
      occupational and recreational physical activity. This questionnaire was validated
      earlier against measures of energy expenditure and cardio-respiratory fitness.
      Participants were ranked into four groups of physical activity. The cohort was
      monitored over 14 years for symptomatic gallstones. The primary outcome was
      hazard ratios (HR) of developing gallstones at 5 years, calculated using Cox
      regression modelling. HRs were adjusted for body mass index, alcohol, hormone
      replacement therapy and parity. Further analysis of a binary variable compared
      the highest level of physical activity against a combination of the lowest three
      levels. RESULTS: After 5 years of follow-up, 135 participants (69.6% women)
      developed symptomatic gallstones. Comparing the highest level of physical
      activity against the lowest three levels, the multivariable analysis at 5 years
      was HR=0.30 (95% confidence interval=0.14-0.64, P=0.002). After 14 years the
      findings were attenuated (HR=0.70, 95% confidence interval=0.49-1.01, P=0.055).
      CONCLUSION: The highest level of physical activity was associated with a 70%
      decreased risk of symptomatic gallstones after 5 years. This association may be
      causal as there are consistent experimental and epidemiological data for a
      protective effect. Physical activity should be accurately measured in studies
      investigating gallstones aetiology.

PMID- 20130469
TI  - Genetic variants promoting smooth muscle cell proliferation can result in diffuse
      and diverse vascular diseases: evidence for a hyperplastic vasculomyopathy.
AB  - Genetic predisposition to early onset of occlusive vascular diseases, including
      coronary artery disease, ischemic stroke, and Moyamoya disease, may represent
      varying presentations of a common underlying dysregulation of vascular smooth
      muscle cell proliferation. We discuss mutations in two genes, NF1 and ACTA2,
      which predispose affected individuals to diffuse and diverse vascular diseases.
      These patients show evidence of diffuse occlusive disease in multiple arterial
      beds or even develop seemingly diverse arterial pathologies, ranging from
      occlusions to arterial aneurysms. We also present the current evidence that both
      NF1 and ACTA2 mutations promote increased smooth muscle cell proliferation in
      vitro and in vivo, which leads us to propose that these diffuse and diverse
      vascular diseases are the outward signs of a more fundamental disease: a
      hyperplastic vasculomyopathy. We suggest that the concept of a hyperplastic
      vasculomyopathy offers a new approach not only to identifying mutated genes that
      lead to vascular diseases but also to counseling and possibly treating patients
      harboring such mutations. In other words, this framework may offer the
      opportunity to therapeutically target the inappropriate smooth muscle cell
      behavior that predisposes to a variety of vascular diseases throughout the
      arterial system.

PMID- 20130470
TI  - Phase I/II trial of the anti-HIV activity of mifepristone in HIV-infected
      subjects ACTG 5200.
AB  - BACKGROUND: Mifepristone is a glucocorticoid receptor inhibitor shown in vitro to
      have anti-HIV activity and anti-simian immunodeficiency virus activity in a
      macaque model. A phase I/II trial was performed to assess the drug's safety and
      anti-HIV activity. METHODS: A 28-day double-blind, placebo-controlled trial of
      mifepristone at doses of 75 mg, 150 mg, and 225 mg given daily was conducted in
      HIV+ persons with CD4+ lymphocyte counts >or=350 cells per cubic millimeter who
      had no recent antiretroviral therapy. RESULTS: Fifty-six male and 1 female
      subjects with a median entry CD4+ lymphocyte count of 555 cells per cubic
      millimeter and plasma HIV-1 RNA of 15,623 copies per milliliter were accrued.
      Forty-five subjects (78.9%) were available for endpoint analysis. In each arm,
      changes from baseline to day 28 in plasma HIV-1 RNA and CD4+ lymphocyte count
      were not significantly different from zero (no change). There was no relationship
      between mifepristone trough concentrations and plasma HIV-1 RNA. Day 28 morning
      plasma cortisol levels were significantly higher in the 150 mg and 225 mg arms
      compared with placebo, confirming biologic activity, and returned to baseline by
      day 56. Serum lipids did not change during the trial. Fasting blood sugar was 2.5
      mg/dL higher on day 28 in the mifepristone arms, but the Homeostasis Model
      Assessment of Insulin Resistance (HOMA-IR) did not change. Three subjects (7.3%)
      receiving mifepristone developed a grade 2 rash. CONCLUSIONS: Mifepristone at
      doses of 75-225 mg daily was safe and well-tolerated, but did not show
      significant anti-HIV activity.

PMID- 20130471
TI  - Antiretroviral prophylaxis to prevent perinatal HIV transmission in St.
      Petersburg, Russia: too little, too late.
AB  - BACKGROUND: We evaluated the influence of type and timing of prophylaxis on
      perinatal HIV transmission in St. Petersburg, Russia. METHODS: We linked
      surveillance data for 1498 HIV-infected mothers delivering from 2004 to 2007 with
      polymerase chain reaction data for 1159 infants to determine predictors of
      transmission. RESULTS: The overall perinatal transmission rate was 6.3% [73 of
      1159, 95% confidence interval (CI) 4.9% to 7.7%]. Among the 12.8% (n = 149) of
      mother-infant pairs receiving full course (antenatal, intrapartum, postnatal)
      dual/triple antiretroviral prophylaxis, the transmission rate was 2.7%. Among the
      1010 receiving less complete regimens (full course zidovudine, single-dose
      nevirapine, or incomplete), transmission ranged from 4.1% to 12.2%. Among the
      28.9% (330) of mothers initiating antiretroviral drugs <or=20 weeks gestation,
      perinatal transmission was 1.8%, compared with 4.0%, 8.6%, and 11.3% for those
      initiating antiretrovirals at 21-28 weeks, 29-42 weeks, or during labor and
      delivery, respectively (P for trend <0.0001). Compared with those initiating
      antepartum prophylaxis <or=20 weeks, those initiating antepartum prophylaxis
      >or=29 weeks (or not at all) had increased transmission odds (adjusted odds
      ratio: 4.9, 95% CI: 1.8 to 12.9; odds ratio: 5.1, 95% CI: 2.0 to 13.1,
      respectively). CONCLUSIONS: In St. Petersburg, the potential for further
      reductions in perinatal transmission is evident, given low transmission among
      women receiving early combination prophylaxis.

PMID- 20130472
TI  - Molecular epidemiology of HIV-1 subtype B, CRF01_AE, and CRF07_BC infection among
      injection drug users in Taiwan.
AB  - OBJECTIVE: An explosive outbreak of HIV-1 circulating recombinant form (CRF)
      07_BC among injection drug users (IDUs) in Taiwan was first reported in 2004 and
      reach the peak in 2005. The objectives of this study were to investigate the
      molecular epidemiology of different HIV-1 subtypes and their associated risk
      factors among Taiwanese IDUs in 2004 and 2005. METHODS: Questionnaires and blood
      specimens were collected from inmates from 4 detention centers and 2 prisons. HIV
      1 subtypes were determined using nested polymerase chain reactions with multiplex
      primers and phylogenetic analyses. A case-control study was conducted to
      elucidate risk factors associated with CRF07_BC infection. RESULTS: A total of
      93.8%, 4%, and 2.2% of 451 inmates with IDU history were infected with CRF07_BC,
      subtype B, and CRF01_AE, respectively. Besides CRF07_BC, a new outbreak of
      CRF01_AE infection was identified among IDUs from central region. Multivariate
      analysis showed that sharing dissolved heroine solution [odds ratio (OR) = 17.2],
      sharing syringes (OR = 34), number of persons sharing syringes (2 vs. 1, OR =
      3.1), and lower educational level (OR = 2.3) were risk factors associated with
      CRF07_BC infection. CONCLUSIONS: Sharing dissolved heroine solution is a
      neglected risk factor associated with HIV-1 infection and it should be emphasized
      in the AIDS education and harm reduction programs immediately.

PMID- 20130473
TI  - Connection domain mutations in treatment-experienced patients in the OPTIMA
      trial.
AB  - OBJECTIVES: To determine the frequency of mutations in the connection domain (CD)
      of HIV reverse transcriptase in treatment-experienced patients in the Options in
      Management with Antiretrovirals trial, their impact on susceptibility to
      antiretroviral (ARV) drugs, and their impact on virologic outcomes. METHODS:
      Baseline plasma ARV genotypes and inferred resistance phenotypes were obtained.
      Frequencies of E312Q, Y318F, G333D, G333E, G335C, G335D, N348I, A360I, A360V,
      V365I, A371V, A376S, and E399G were compared with a treatment-naive population.
      The association of CD mutations with inferred IC50 fold changes to nucleos(t)ide
      reverse transcriptase inhibitors was evaluated. Univariate and multivariate
      analyses examined the association of CD mutations with a >1 log10 per milliliter
      decrease in HIV viral load after 24 weeks on a new ARV regimen. RESULTS: Higher
      CD mutation rates were seen in Options in Management with Antiretrovirals
      patients (n = 345) compared with a treatment-naive population. CD mutations were
      associated with increased inferred IC50 fold changes to abacavir, stavudine,
      tenofovir, and zidovudine. On univariate analysis, A371V was associated with lack
      of virologic response, as was having any CD mutation on multivariate analysis.
      CONCLUSIONS: CD mutations are frequent in treatment-experienced populations. They
      are associated with reduced susceptibility to some nucleos(t)ide reverse
      transcriptase inhibitors and with a diminished response to ARV therapy.

PMID- 20130474
TI  - Unusual "traction" exostosis of the femoral diaphysis with sciatic nerve
      compression.

PMID- 20130475
TI  - Lenalidomide for the treatment of cryoglobulinemia and undifferentiated
      spondyloarthropathy in a patient with multiple myeloma.

PMID- 20130476
TI  - Calciphylaxis in a hemodialysis patient on corticosteroids and etanercept for
      psoriatic arthritis.

PMID- 20130477
TI  - Mycobacterium bovis discitis as a complication of intravesical Bacillus Calmette
      Guerin therapy.
AB  - We report a culture-proven case of Mycobacterium bovis discitis in a 67-year-old
      man who had received intravesical Bacillus Calmette-Guerin for bladder cancer 5
      years previously. He presented with severe low back pain, and imaging revealed
      features of discitis and paraspinal abscesses. On aspiration of the abnormal
      tissue, culture confirmed infection with M. bovis. Quadruple antituberculous
      therapy was commenced at this stage, with a subsequent good clinical response.
      Hematogenous spread of M. bovis is a rare, often delayed, complication of
      intravesical BCG therapy, but early appropriate treatment can result in a good
      prognosis.

PMID- 20130478
TI  - Reversible heart failure in a patient receiving etanercept for ankylosing
      spondylitis.
AB  - A 42-year-old man with ankylosing spondylitis that was refractory to nonsteroidal
      anti-inflammatory drugs as well as various disease-modifying antirheumatic drugs
      was subjected to anti-TNF compounds. Administration of infliximab and adalimumab
      gave excellent clinical response but was discontinued due to adverse events.
      Introduction of etanercept was also clinically effective but followed by
      development of severe heart failure. Discontinuation of etanercept led to control
      of heart function. The unusually though potentially life-threatening possibility
      of heart failure secondary to anti-TNF use in ankylosing spondylitis merits
      attention.

PMID- 20130479
TI  - Microscopic polyangiitis presenting as early cardiac tamponade.

PMID- 20130480
TI  - Clinical value of single versus composite provocative clinical tests in the
      assessment of painful shoulder.
AB  - OBJECTIVES: The aims of the present study were to investigate the clinical value
      of the provocative clinical tests and propose a composite index for the
      assessment of painful shoulder, using ultrasonography (US) as reference method.
      METHODS: Two hundred three patients with painful shoulder underwent both clinical
      and US evaluations. The physical examination was carried out performing the
      Hawkins, Jobe, Patte, Gerber, and Speed tests. Each test was included in a
      composite index namely, SNAPSHOT (Simple Numeric Assessment of Pain by SHOulder
      Tests). The US examination was performed by a rheumatologist experienced in US
      and blinded to clinical findings. Sensitivity, specificity, positive and negative
      predictive values, positive and negative likelihood ratio of each clinical test
      were calculated. The receiver operating characteristic (ROC) curve analysis was
      used to assess the performance of the composite SNAPSHOT index. RESULTS:
      Sensitivity was low for the clinical diagnosis of all shoulder abnormalities. The
      highest sensitivity and smallest negative likelihood ratio were found for the
      Hawkins (63.88% and 0.50%) and Patte (62.21% and 0.52%) tests. Specificity was
      good for Speed (76.33%), Gerber (75.42%), and Patte (74.20%) tests. Patte and
      Speed tests were the most accurate (71.12% and 66.41%, respectively). The
      calculated area under the ROC curve related to the SNAPSHOT composite index was
      0.881 +/- 0.026. With an optimal cut-off point of 3, the sensitivity and
      specificity were 75.8% and 87.5%, respectively. CONCLUSION: The results of the
      present study showed that SNAPSHOT is a feasible, informative and quantitative
      composite index for the assessment of painful shoulder in the clinical setting.

PMID- 20130481
TI  - Nonspecific low back pain during childhood: a retrospective epidemiological study
      of risk factors.
AB  - OBJECTIVES: In contrast to what was believed in the past, nonspecific low back
      pain is a fairly frequent condition in children, whose pathophysiology remains
      unclear as yet. Although many factors have been implicated in its development,
      results are often contradictory. METHODS: Our study aims to examine most of the
      reasons investigated in the international literature, as well as the previously
      unexamined impact of passive smoking in its clinical appearance. It is a
      retrospective study that investigates the symptom of nonspecific low back pain
      during a 12-month period before the visit of children to our department. The
      research included 692 children aged 7.5 to 14 years. The data were collected
      using a semi-structured questionnaire, which included a mix of open and closed
      questions, followed by physical examination during their visit. RESULTS: A total
      of 153 children were considered to present nonspecific low back pain during the
      previous year. The determinant factors appear to be greater age, the male sex,
      larger height, increased weight, dissatisfaction with school chairs, the clinical
      presentation of back pain in at least 1 parent, and coexisting anatomic
      orthopedic conditions. On the contrary, the weight of the school bag, the way in
      which it was carried and participation in sports, as well as the time spent by
      children in front of the TV or PC playing video or play station games, did not
      appear to have a statistically significant correlation with its appearance. In
      general, passive smoking does not appear to be a risk factor (P[r] = 0.341), and
      does not seem to play a leading role in the etiology of the condition.
      Furthermore, even the heaviness of parental smoking (over 20 cigarettes a day)
      does not seem to alter the appearance of the disease. The effect of nonspecific
      low back pain in children's activities was measured using Hannover Functional
      Ability and Rolland Morris questionnaires, appropriately modified to childhood,
      where he found a moderate or severe restriction of activity in 23.52% (score >5)
      and 19.61% (score >6), respectively. CONCLUSIONS: The data analysis shows that
      nonspecific low back pain in children is a benign disorder with an unknown
      pathophysiological mechanism. Many anthropometric characteristics and
      environmental factors are implicated, but to a different degree each time.
      Passive smoking as well as the heaviness thereof does not appeal to play in
      important role in its clinical presentation. Further investigation is deemed
      necessary to determine the existence of other risk factors, as well as the level
      of their participation in the condition's pathophysiology.

PMID- 20130482
TI  - Tai chi improves physical function in older Chinese women with knee
      osteoarthritis.
AB  - BACKGROUND: Tai chi (TC) is proposed as a potential option for the management of
      osteoarthritis (OA), however, its beneficial effect on patients with knee OA has
      not been convincing. OBJECTIVES: To evaluate the effect of a 24-week TC program
      on physical functions in older Chinese women with knee OA. METHODS: Thirty-five
      older Chinese women with knee OA were randomized into TC group (n = 18) and
      attention control (wellness education and stretching) group (n = 17). Subjects in
      the TC group practiced the 24-form simplified Yang-style TC 2 to 4 times a week
      for 24 weeks with frequency gradually increased. Physical function was assessed
      using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), 6
      minute walk distance and stair climb time. RESULTS: Compared with the control
      group, the participants in TC group had statistically significant improvements in
      changes of the WOMAC total score (6.18 +/- 2.13 vs. 1.71 +/- 2.73, P = 0.000),
      the WOMAC pain subscale (1.36 +/- 0.22 vs. 0.07 +/- 1.00, P = 0.001), the WOMAC
      stiffness subscale (0.66 +/- 0.25 vs. 0.05 +/- 0.38, P = 0.043), the WOMAC
      function subscale (6.17 +/- 1.96 vs. 1.72 +/- 2.63, P = 0.000), the 6-minute walk
      distance (32.43 +/- 14.20 vs. 6.67 +/- 16.76, P = 0.003), and the stair climb
      time (2.27 +/- 0.74 vs. 0.27 +/- 1.24, P = 0.001). CONCLUSIONS: This study
      suggests that TC provides a safe, feasible and useful exercise option for older
      Chinese female patients with knee OA.

PMID- 20130483
TI  - Atypical insufficiency fracture of the tibia associated with long-term
      bisphosphonate therapy.
AB  - Osteoporosis is a major public health threat affecting millions of individuals in
      the United States. Bisphosphonate therapy is currently recognized as a first-line
      treatment of osteoporosis through the inhibition of osteoclast activity. Concerns
      have been raised about potential oversuppression of bone turnover and the
      development of atypical skeletal fragility associated with long-term use of
      bisphosphonates. A number of case reports in the literature have documented
      atypical insufficiency fractures in patients on long-term bisphosphonate therapy.
      This case outlines what we believe is the second documented atypical tibial
      insufficiency fracture in a patient on long-term bisphosphonate therapy, and
      highlights the need for increased awareness of atypical insufficiency fractures
      as well as the need for more data concerning the long-term effects of
      bisphosphonate therapy.

PMID- 20130484
TI  - Primary signet-ring carcinoma (SRC) of the lung: a population-based epidemiologic
      study of 262 cases with comparison to adenocarcinoma of the lung.
AB  - BACKGROUND: The presence of signet-ring cell component has been described as a
      prominent feature of EML4-ALK positive non-small cell lung cancer. We
      investigated the clinicopathologic features and survival outcome of primary
      signet-ring carcinoma (SRC) of the lung with comparison to adenocarcinoma of the
      lung. METHODS: Retrospective population-based analysis of histologically
      diagnosed primary SRC of the lung in the California Cancer Registry between 1989
      and 2006 with comparison with adenocarcinoma of the lung. RESULTS: Two hundred
      sixty-two histologically diagnosed primary SRC of the lung were compared to
      50,089 patients with lung adenocarcinoma. Patients with primary SRC of the lung
      were significantly younger than patients with adenocarcinoma, with a
      significantly higher proportion of poorly differentiated tumor and stage IV
      disease. There was no difference in the distribution of gender and ethnicity
      among patients with SRC when compared to patients with adenocarcinoma. Subset
      analysis of patients with available smoking status revealed never smokers
      comprised a significantly higher proportion of patients with SRC (30.8%) when
      compared to patients with adenocarcinoma (11.0%; p = 0.0013). Never smokers with
      SRC tended to be younger with a trend to improved survival (median age = 55
      years, median overall survival [OS] = 8 months) than ever smokers with SRC
      (median age = 59 years, median OS = 4.5 months). Patients with SRC had decreased
      OS (versus adenocarcinoma; unadjusted hazard ratio = 1.507; 95% confidence
      interval: 1.326-1.714; p < 0.0001) and was an independent unfavorable prognostic
      factor by multivariate analysis (versus adenocarcinoma, hazard ratio 1.214, 95%
      confidence interval: 1.068-1.381; p = 0.0030). CONCLUSIONS: Primary SRC of the
      lung is a rare subtype of adenocarcinoma, carries a worse prognosis when compared
      to adenocarcinoma and shares many of the recently identified clinicopathologic
      characteristics ascribed to EML4-ALK positive non-small cell lung cancer.

PMID- 20130485
TI  - Changes of circulating transforming growth factor-beta1 level during radiation
      therapy are correlated with the prognosis of locally advanced non-small cell lung
      cancer.
AB  - INTRODUCTION: We hypothesized that plasma transforming growth factor-beta1 (TGF
      beta1) level and its dynamic change are correlated with the prognosis of locally
      advanced non-small cell lung cancer (NSCLC) treated with radiation therapy (RT).
      METHODS: Patients with stage IIIA or IIIB NSCLC treated with RT with or without
      chemotherapy were eligible for this study. Platelet poor plasma was collected
      from each patient within 1 week before RT (pre-RT) and at the 4th week during RT
      (during-RT). TGF-beta1 level was measured with enzyme-linked immunosorbent assay.
      The primary end point was overall survival (OS) and the secondary end point was
      progression-free survival (PFS). Kaplan-Meier and Cox regression were used for
      risk factor evaluation. RESULTS: A total of 65 patients were eligible for the
      study. The median OS and PFS were 17.7 and 13.7 months, respectively. In
      univariate analysis, performance status, weight loss, radiation dose, and TGF
      beta1 ratio (during-RT/pre-RT TGF-beta1 level) were all significantly correlated
      with OS. In the multivariate analysis, performance status, radiation dose, and
      TGF-beta1 ratio were still significantly correlated with OS. The median OS was
      30.7 months for patients with TGF-beta1 ratio <or=1 versus 13.3 months for those
      with TGF-beta1 ratio more than 1 (p = 0.0029); and the median PFS was 16.8 months
      versus 7.2 months, respectively (p = 0.010). CONCLUSIONS: In locally advanced
      NSCLC, the decrease of TGF-beta1 level during RT is correlated with favorable
      prognosis.

PMID- 20130486
TI  - Use of force by law enforcement: an evaluation of safetyand injury.
AB  - BACKGROUND: Little is known about the frequency and types of injuries sustained
      from law enforcement use of force (UOF). The purpose of this study was to examine
      injury patterns and subject conditions after law enforcement UOF under real-life
      conditions. METHODS: A retrospective cohort design was used to examine every UOF
      by a single police department from January through December, 2006. Data were
      collected from law enforcement UOF forms as well as medical records and included
      conditions surrounding the UOF, medical histories, and data from emergency
      department (ED) evaluations and hospital admissions. RESULTS: Of 888 individuals
      subjected to force during the study period, 86.9% were men and the average body
      mass index was 25.8. Ages ranged from 10 to 77 years; juveniles comprised 5.6%.
      Of the types of force used by police, 73.7% were blows with arms or legs; 15.9%
      were Taser, 4.6% were capsicum spray, 1.7% were K-9, 0.7% were impact weapons,
      and 0.2% were firearms. Of the 630 (70.9%) with medical records, 78.7% had a
      substance abuse or psychiatric history. ED evaluations occurred for 187 (21.1%
      of) incidents. When laboratory workup occurred, 75.5% had positive urine
      toxicology and 45.9% had positive ethanol levels. Admission occurred in 15.5%
      (29) of ED presentations (3.3% of all subjects); of these, 9 (31.0%) were for UOF
      related injury. Two subjects in the study died: one as a result of firearm injury
      and one by suicide after UOF; both were declared dead on scene. DISCUSSION:
      Significant injuries related to law enforcement UOF in one city were rare and the
      only deaths were related to firearm use. A large percentage of those subjected to
      UOF had diagnoses of substance abuse and/or psychiatric conditions, and most
      hospital admissions were for problems unrelated to the UOF.

PMID- 20130487
TI  - Proper estimation of blood loss on scene of trauma: tool or tale?
AB  - BACKGROUND: Visually estimated amount of blood loss may influence decision making
      in the prehospital setting. The purpose of this study was to determine the
      ability and accuracy of paramedics and emergency physicians to visually estimate
      a volume of external blood loss and the influence of different vital signs.
      METHODS: In a prospective, blinded, observational design, participants were asked
      to visually estimate the amount of blood in six simulated trauma scenarios.
      Casualties were provided with a simulated injury, and a certain amount of
      artificial blood that was poured on the casualties' clothing and on the floor. In
      addition, vital signs (i.e., blood pressure and heart rate) were given. Each two
      moulage patients were provided with the same injury pattern and the same
      simulated blood loss. Although one patient seemed to be normovolemic, the other
      seemed to be hypovolemeic by the given vital signs. RESULTS: With regard to all
      given amounts of blood loss, providing vital parameters suggesting instability
      (i.e., low blood pressure, high heart rate) led to a higher estimation of the
      lost blood volume in both paramedics and emergency physicians. However,
      estimations were influenced impressively by the given parameters. For both stable
      and unstable patients, small actual volumes were overestimated, whereas higher
      volumes tended to be underestimated. Neither occupational status (emergency
      physician or paramedic) nor gender or level of experience influenced accuracy of
      estimated blood loss significantly.

PMID- 20130488
TI  - Quantification of reaming debris at the fracture gap of diaphyseal A3 femur
      fractures after reamed intramedullary nailing and using an intramedullary
      application system.
AB  - BACKGROUND: After reamed nailing in long bones, there is a negligible amount of
      reaming debris at the fracture gap of A2 and A3 fractures. The aim of this study
      was to show whether there are differences between reamed nailing and reamed
      nailing with controlled intramedullary application of reaming debris at the
      fracture gap with an intramedullary application device. METHODS: In this trial,
      12 human femur specimens were used. On the medullary isthmus, 12 A3 fractures
      were artificially produced. Afterward, reduction was done by a monocortical
      external fixator, and closure of the fracture gap was done with a latex finger
      tip. Intramedullary reaming was performed for up to 10% of the bone cortex. In
      six femurs, the reaming procedure alone was performed, and in six human femurs,
      additional controlled application of reaming debris was done. For fixation, an
      intramedullary plastic implant was used. The region of interest was scanned with
      the MU-CT 80, and the fracture gap was contoured with digital imaging software.
      The threshold for the reaming debris was set at 365.6 mgHA/cm3. The analysis of
      the bone debris located at the fracture gap was measured by percent of debris
      volume to gap volume. For statistical analysis, the Wilcoxon test was used and a
      level of significance of p < 0.05 was chosen. RESULTS: The fracture gap volume
      ranged from 7 mm3 to 29 mm3 without differences in both the groups. In the group
      without controlled intramedullary application, there was a median bone volume of
      0.37 mm3 found at the fracture gap. In the group with controlled intramedullary
      application, a median of 2.2 mm3 of bone debris was found. The degree of filling
      of the fracture gap with bone debris was 2% without additional application and
      13% with additional application, using the newly developed application device.
      CONCLUSIONS: The results show that reaming debris at the fracture gap without
      additional application is negligible. When using an intramedullary application
      device, the amount of reaming debris at the fracture gap can be increased
      significantly.

PMID- 20130489
TI  - Diagnosis of unstable cervical spine injuries: laboratory support for the use of
      axial traction to diagnose cervical spine instability.
AB  - BACKGROUND: The ability to detect damage to the intervertebral structures is
      critical in the management of patients after blunt trauma. A practical and
      inexpensive method to identify severe structural damage not clearly seen on
      computed tomography would be of benefit. The objective of this study was to
      assess whether ligamentous injury in the subaxial cervical spine can be reliably
      detected by analysis of lateral radiographs taken with and without axial
      traction. METHODS: Twelve fresh, whole, postrigor-mortis cadavers were used for
      this study. Lateral cervical spine radiographs were obtained during the
      application of 0 N, 89 N, and 178 N of axial traction applied to the head.
      Progressive incremental sectioning of posterior structures was then performed at
      C4-C5 with traction imaging repeated after each intervention. Intervertebral
      distraction was analyzed using computer-assisted software. RESULTS: Almost
      imperceptible intervertebral separation was found when traction was applied to
      intact spines. In the subaxial cervical spine, the average posterior disc height
      consistently increased under traction in severely injured spines. The average
      disc height increase was 14% of the C4 upper endplate width, compared with an
      average of 2% in the noninjured spines. A change of more than 5% in posterior
      disc height under traction was above the 95% confidence interval for intact
      spines, with sensitivity of 83% and specificity of 80%. Applied force of 89 N (20
      lb) was sufficient to demonstrate injury. The combination of assessing alignment
      and distraction under traction increased both the sensitivity and specificity to
      nearly 100%. CONCLUSION: This study supports further clinical investigations to
      determine whether low-level axial traction may be a useful adjunct for detecting
      unstable subaxial cervical spine injuries in an acute setting.

PMID- 20130490
TI  - Calcaneocuboid joint involvement in calcaneal fractures.
AB  - BACKGROUND: The reported incidence of calcaneocuboid joint (CCJ) involvement in
      calcaneal fractures varies considerably. It is largely unknown to what extent CCJ
      involvement accounts for outcome in these fractures. Therefore, the goal of this
      study was to analyze the incidence and effects of CCJ involvement in calcaneal
      fractures. METHODS: The clinical records of 106 patients, treated between 2000
      and 2004, were reviewed for fracture classification, injury mechanism, surgical
      treatment, and complications. In a prospective cross-sectional study, 44 patients
      were assessed clinically (SF-36 American Orthopaedic Foot and Ankle Society
      score) and radiographically. Gait analysis was performed using dynamic
      pedography. RESULTS: Sixty-eight percent of all fractures had involvement of the
      CCJ. Fractures with CCJ involvement were caused by a more severe injury than
      fractures without CCJ involvement (Mann-Whitney U test, p = 0.03); this is
      reflected by a strong association between CCJ involvement and fracture
      classification (Spearman, p < 0.006). Patients with involvement of the CCJ
      especially those with a postoperative step in the CCJ-achieved a lower SF-36
      score as well as a lower American Orthopaedic Foot and Ankle Society score than
      patients without CCJ involvement. CCJ involvement was associated with more
      difficulties in walking on rough surface (Spearman, p = 0.020). Limitations
      during gait were confirmed by dynamic pedography. Grading of posttraumatic
      osteoarthritis was associated with fracture classification (chi test p < 0.02)
      and quality of reduction (chi test p < 0.01). CONCLUSIONS: These results indicate
      that calcaneal fractures with involvement of the CCJ are associated with more
      severe trauma and worse outcome. Thus, the CCJ should be given more credit during
      surgery and in our research efforts.

PMID- 20130492
TI  - Estrogen therapy and risk of breast cancer in postmenopausal women: a case
      control study and results of a multivariate analysis.
AB  - OBJECTIVE: Several randomized trials and observational studies show that the use
      of hormone therapy (HT) increases the risk of breast cancer (BC). The aim of this
      study was to assess the effects of exposure to both HT and oral contraceptives
      (OCs) on BC risk in postmenopausal women, all residing in the same metropolitan
      area. METHODS: Data regarding a series of 238 consecutive postmenopausal women
      with infiltrating ductal carcinoma (cases) and 255 randomly selected age-matched
      healthy women (controls) were reviewed. Odds ratios for no breast-feeding and HT
      and OC use were 1.82 (95% CI, 1.20-2.77), 2.49 (95% CI, 1.73-3.58), and 2.06 (95%
      CI 1.14-3.70), respectively. RESULTS: Four independent variables (years between
      menarche and menopause, breast-feeding, OC use, and HT use) were included in the
      final multivariate analysis using logistic regression. The cumulative odds ratio
      calculated from the observed versus predicted values, obtained using the logistic
      regression function, was 4.55 (95% CI, 2.13-9.71), whereas the cumulative risk of
      common exposure to both OCs and HT was 2.77 (95% CI, 1.44-5.32). The logistic
      model correctly classified 67.5% (95% CI, 63.2-71.5) of cases. The receiver
      operating characteristic (ROC) curve of the complete logistic function showed a
      fair area of accuracy (0.77; 95% CI, 0.72-0.81). CONCLUSIONS: Our results show
      that the risk of common exposure to both OCs and HT increases in women with other
      risk factors. However, several parameters traditionally considered in
      epidemiological studies do not have the same weight in each local community,
      suggesting the need to create different models to correctly select the high-risk
      population.

PMID- 20130493
TI  - Validity and cultural equivalence of the standard Greene Climacteric Scale in
      Hong Kong.
AB  - OBJECTIVES: The aim of this study was to translate the standard Greene
      Climacteric Scale (GCS) and a urogenital symptom scale into colloquial Chinese
      (Hong Kong) and test their validity and reliability in Hong Kong Chinese women.
      METHODS: The scales were translated with standard techniques, and cross-cultural
      construct validity, internal consistency, test-retest reliability, and
      responsiveness were tested on samples of women aged 40 to 60 years recruited from
      the community. RESULTS: A total of 611 women, with mean (SD) age of 48.9 (5.3)
      years, provided completed scales for the study. Confirmatory factor analysis
      demonstrated construct validity of the translated standard GCS. The items were
      found to have good homogeneity in measuring the scale concepts (Cronbach alpha >
      0.7). But the three-item urogenital scale had poor internal consistency (Cronbach
      alpha = 0.43), and a combination of this scale with the standard GCS resulted in
      a reduced model fit to the data. Test-retest reliability for the GCS was good on
      women recruited for a retest (n = 52). The translated GCS was found to be
      responsive to change over time (effect size, 0.59; n = 19). CONCLUSIONS: The
      Chinese (Hong Kong) version of the standard GCS is a valid and cultural
      equivalent instrument. Our data do not support inclusion of the urogenital scale
      to the standard GCS. Measurement of urogenital symptoms is subject to further
      study.

PMID- 20130494
TI  - Association of common variants of CYP4A11 and CYP4F2 with stroke in the Han
      Chinese population.
AB  - OBJECTIVE: 20-Hydroxyeicosatetraenoic acid has been shown to play an important
      role in cerebral vascular function. We hypothesized that polymorphisms in genes
      encoding 20-Hydroxyeicosatetraenoic acid synthesizing enzymes might confer
      susceptibility to stroke. METHODS AND RESULTS: To test the hypothesis, haplotype
      tagging single nucleotide polymorphisms and potential functional polymorphisms of
      CYP4A11 and CYP4F2 genes were genotyped in 558 ischemic stroke patients, 221
      hemorrhagic stroke patients and 557 controls. The association analyses were
      performed at both single nucleotide polymorphism and haplotype levels. We further
      verified our findings in an independent cohort of 551 ischemic stroke cases and
      48 hemorrhagic stroke cases and 694 unaffected controls. We identified CYP4A11 C
      296T and CYP4F2 V433M were associated with significantly increased risk of
      ischemic stroke (CT+TT vs. CC, adjusted odds ratio: 1.50, 95% confidence
      interval: 1.17-1.93, Pcombined=0.001, Pcorr=0.008; V/M+M/M vs. V/V, odds ratio:
      1.38, 95% confidence interval: 1.15-1.65, Pcombined=5.6x10, Pcorr=0.005,
      respectively). Interestingly, the effects of CYP4F2 V433M on ischemic stroke in
      our study was only evident in male individuals. CONCLUSION: Our results suggest
      that genetic variation in CYP4A11 and CYP4F2 alters susceptibility to stroke in
      the Han Chinese population.

PMID- 20130495
TI  - Controlled organ donation after cardiac death: potential donors in the emergency
      department.
AB  - BACKGROUND.: The continuing shortfall of organs for transplantation has increased
      the use of donation after cardiac death (DCD). We hypothesized that some patients
      who undergo tracheal intubation in the emergency department (ED) and who are
      assessed for, but not admitted to, critical care might have potential for
      controlled DCD. METHODS.: We identified all patients who underwent tracheal
      intubation in the ED between 2004 and 2008 and studied their records to identify
      those not admitted to an intensive care unit. We reviewed the notes of patients
      extubated in the ED to ascertain the diagnosis, management, outcome, and
      potential exclusion criteria for controlled DCD. RESULTS.: One thousand three
      hundred seventy-four patients had tracheal intubation performed in the ED; 1053
      received anesthetic drugs to assist intubation. Three hundred seventy-five
      patients were not admitted to intensive care unit; 235 died during resuscitation
      in the ED. Of the 49 patients extubated in the ED to allow terminal care, 26 were
      older than 70 years and 18 had comorbidities precluding organ donation. Fourteen
      patients could have been considered for DCD, but in eight, the time from
      extubation to death exceeded 2 hr. Thus, six patients might have been missed as
      potential controlled DCD from the ED in this 5-year period. CONCLUSIONS.:
      Identification of potential donors after cardiac death in the ED with appropriate
      use of critical care for selected patients may contribute to reducing the
      shortfall of organs for transplantation, although numbers are likely to be small.
      This area remains controversial and requires further informed discussion between
      emergency and critical care doctors and transplant teams.

PMID- 20130496
TI  - Abnormal glucose metabolism and metabolic syndrome in non-diabetic kidney
      transplant recipients early after transplantation.
AB  - BACKGROUND: Abnormal glucose metabolism (AGM) and metabolic syndrome (MS) are
      individually associated with a poor cardiovascular outcome in kidney transplant
      recipients. We prospectively studied the relationship between AGM and MS in non
      diabetic kidney transplant recipients early after transplantation. METHODS: A
      total of 203 de novo kidney transplant recipients underwent standard 2-hr glucose
      tolerance test 10 weeks after transplantation. Demographic and clinical
      characteristics were collected. AGM was defined as impaired fasting glucose,
      impaired glucose tolerance, and new onset diabetes after transplant according to
      the WHO criteria, and MS was defined according to the National Cholesterol
      Education Expert Panel criteria. RESULTS: Overall, 97 patients (47.8%) met the
      diagnosis of AGM and 98 patients (48.3%) met the criteria of MS. AGM and MS are
      highly associated (chi, P<0.001). Fasting plasma glucose levels before the
      transplant are independent predictors common for AGM and MS. Age predicts AGM
      with and without MS, whereas body mass index before transplant predicts MS.
      Patients with impaired glucose tolerance and new-onset diabetes after transplant
      displayed significant worsening of their fasting plasma glucose levels during the
      10-week observational period. MS and the components of MS, but not AGM, were
      associated with reduced transplant renal function (P=0.002). CONCLUSION: The
      early screening of AGM and MS should be emphasized, and the role of early
      therapeutic interventions aimed at both conditions explored. The long-term follow
      up of these patients will yield more insight on the significance of such
      findings.

PMID- 20130497
TI  - Cancer-related infertility in survivorship.
AB  - INTRODUCTION: To empirically assess and describe the emotional, sexual, and
      physical impact of cancer-related infertility on gynecologic cancer survivors.
      METHODS: The study was composed of 88 survivors of cervical, endometrial/uterine,
      ovarian cancer, and gestational trophoblastic disease who experienced impaired or
      loss of fertility as a result of treatment. Patient age ranged from 21 to 49
      years. Participants completed a 1-time self-report survey, including medical and
      demographic information and empirical measures of mood (Center for Epidemiologic
      Studies Depression Scale), distress (Impact of Event Scale), sexual function
      (Female Sexual Function Index), and menopause (Menopausal Symptom Checklist).
      RESULTS: Eighty-four (96%) of the 88 enrolled patients had undergone a surgical
      intervention as part of their cancer treatment. Sixty-three patients (77%)
      reported clinically significant levels of distress in relation to loss of
      fertility or impaired fertility. Survivors' levels of distress (P < 0.0001) and
      depression (P < 0.0001) were associated with the severity and number of
      menopausal symptoms reported. Patients who retained functioning ovaries (partial
      fertility) (41%, n = 36) reported being less bothered by menopausal symptoms (P =
      0.01) and having higher sexual functioning than those with ovarian failure (P <
      0.0001). CONCLUSIONS: The emotional and physical impact of impaired or loss of
      fertility can be complex and long lasting, with women experiencing high levels of
      distress, menopausal symptoms, and changes in sexual function persisting into
      survivorship. Future research should focus on the development of strategies to
      identify, monitor, and address, in a clinical care setting, the issues these
      cancer survivors face. Alternate family-building strategies should also be
      explored before treatment and/or upon treatment completion when feasible.

PMID- 20130498
TI  - Oviductal glycoprotein (OVGP1, MUC9): a differentiation-based mucin present in
      serum of women with ovarian cancer.
AB  - INTRODUCTION: Epithelial ovarian carcinomas are highly lethal because most are
      detected at late stages. A previous immunohistochemical analysis showed that
      oviductal glycoprotein 1 (OVGP1), a secretory product of the oviductal epithelium
      under estrogen dominance, is produced predominantly by borderline and low-grade
      malignant epithelial ovarian tumors. In the present study, we investigated OVGP1
      as a possible serum marker for the detection of ovarian cancer. METHODS: We
      generated a highly specific monoclonal antibody, clone 7E10, to human OVGP1.
      Using 7E10 and a polyclonal antibody, a sandwich enzyme-linked immunosorbent
      assay was developed to assay OVGP1 levels in 135 normal sera, and sera from 21
      benign tumors, 12 borderline tumors, and 87 ovarian cancers (18, grade 1-2
      serous; 44, grade 3 serous; 10, mucinous; 10, clear cell; and 5, endometrioid).
      RESULTS: Using a 95% confidence interval cutoff from the mean of normal
      postmenopausal sera, median OVGP1 levels were elevated in the sera from 75% of
      the women with borderline tumors and 80% of the women with mucinous, 60% with
      clear cell, 59% with grade 1 and 2 serous, 22% with grade 3 serous, and 0% with
      endometrioid carcinomas. By stage, OVGP1 levels were highest in the sera from the
      borderline tumors, stage I and II serous carcinomas, and mucinous carcinomas.
      OVGP1 levels varied independently of cancer antigen 125 (CA125). CONCLUSIONS:
      Increases in OVGP1 serum levels vary with ovarian tumor histotypes and stages.
      Being differentiation based, OVGP1 seems to detect a different spectrum of
      ovarian epithelial cancers than other markers and thus should be a useful adjunct
      for more accurate detection, particularly of early serous ovarian cancers and
      mucinous carcinomas, which tend to lack increased CA125.

PMID- 20130499
TI  - Effects of oxidized regenerated methylcellulose on lymphocyst formation and
      peritoneum in gynecologic cancer patients.
AB  - HYPOTHESIS: The role of oxidized regenerated methylcellulose (ORC) in the
      lymphocyst formation after systematic lymphadenectomy. METHODS AND STUDY DESIGN:
      This was a retrospective case-control study. Patients with gynecologic cancer who
      underwent systematic lymphadenectomy from May 2000 to April 2006 were considered.
      Retroperitoneal "no closure" method was performed in all patients. Two groups
      were identified according to ORC use. The lymphocysts were evaluated via
      ultrasonography/computed tomography/magnetic resonance imaging between the third
      and sixth months after surgery. RESULTS: The overall lymphocyst incidence was
      found to be 75 (29.8%) of 252, and lymphocyst incidence in the ORC and control
      groups was 45 (30%) of 150 and 30 (29.4%) of 102, respectively. The mean (SD)
      total number of extracted lymph nodes in the ORC group was 27.5 (10.6), which was
      significantly higher than that in the control group (22.1 [10.8]; P = 0.001).
      Duration of drain was significantly longer in the ORC group (P = 0.028). However,
      when confounding variables were included into the binary logistic regression
      analysis for the prediction of the duration of drains, only the stage of disease
      predicted the duration of drains. CONCLUSIONS: Use of ORC does not seem to affect
      lymphocyst formation. Oxidized regenerated methylcellulose use does not affect
      the duration of drains, hence ORC does not seem to pose a stimulatory effect on
      the peritoneum.

PMID- 20130500
TI  - Stromal compartment as a survival prognostic factor in advanced ovarian
      carcinoma.
AB  - OBJECTIVE: We investigated the prognostic significance of stromal compartment on
      the overall survival of patients with advanced epithelial ovarian cancer.
      METHODS: We evaluated retrospectively the stroma proportion of the tumor surgical
      specimens of 194 patients with stages III and IV disease, using histochemical
      staining and fully automatic virtual slide processing. The prognostic
      significance of stroma proportion and clinical parameters were evaluated using
      log-rank test and Cox regression. RESULTS: Stroma proportion was found to be an
      independent prognostic factor by both univariate (P = 0.016) and multivariate
      analyses (hazards ratio = 1.45, P = 0.011). CONCLUSION: The present data indicate
      that a high stroma proportion is related to a poor prognosis of stage III and IV
      ovarian carcinomas.

PMID- 20130501
TI  - Primary radical surgery in elderly patients with epithelial ovarian cancer:
      analysis of surgical outcome and long-term survival.
AB  - OBJECTIVE: Geriatric population life expectancy is increasing and so is the
      incidence of epithelial ovarian cancer (EOC) in elderly women. The aim of our
      study was to determine the impact of radical cytoreductive surgery, the
      cornerstone of clinical management in primary EOC, in this population with
      special regard to the associated morbidity. METHODS: Through a pooled data
      analysis, cancer-related patient characteristics, intraoperative tumor pattern,
      and surgical and clinical outcomes were evaluated according to a validated
      documentation data collection tool. Kaplan-Meier curves were calculated for
      overall survival (OS). The Cox regression analysis was performed to identify
      independent predictors of mortality. RESULTS: One hundred one EOC patients older
      than 69 years (mean [SD] age, 75.54 [4.49] years) were evaluated. The mean (SD)
      follow-up period was 22.63 (22.92) months. Advanced International Federation of
      Gynecology and Obstetrics stage III (60.4%) was the most common tumor stage. A
      complete tumor resection was achieved in 45 patients (44.6%) with an associated
      complication rate of 40.6%. The postoperative mortality was 6%. The mean OS was
      47.29 months (95% confidence interval, 36.24-58.34). The multivariate analysis
      identified age older than 75 years, incomplete tumor resection, and absence of
      adjuvant chemotherapy to negatively affect OS. CONCLUSIONS: Radical surgery for
      primary EOC obtaining complete tumor resection is associated with a significantly
      prolonged OS in elderly patients (> or =70 years). The increased postoperative
      morbidity must be considered, underlining the high requirement for special
      interdisciplinary postoperative management in this special collective.

PMID- 20130502
TI  - Comparison of computed tomography and magnetic resonance imaging in cervical
      cancer brachytherapy target and normal tissue contouring.
AB  - OBJECTIVE: To evaluate the differences between target and normal tissue
      delineation between magnetic resonance imaging (MRI) and computed tomography (CT)
      in cervical cancer patients and to explore the differences in dosimetry after
      brachytherapy planning. METHODS: High-dose-rate brachytherapy was performed on 11
      patients. Planning CT and MRI were performed with tandem and ring in place. The
      radiation oncologist contoured the rectum, the bladder, the sigmoid, and the high
      risk clinical target volume (HR-CTV) on CT and MRI. The values compared between
      CT and MRI included D90 and D100 to HR-CTV; coronal, sagittal, and axial
      measurements of HR-CTV; and minimum dose to most irradiated 0.1-, 0.5-, 1.0-, and
      2.0-cm volumes for the organs at risk (OAR). Doses were converted to the
      equivalent dose in 2 Gy by applying the linear quadratic model. Volume
      optimization was also performed, and the above parameters were evaluated.
      RESULTS: Magnetic resonance imaging showed a significantly greater HR-CTV length
      in the sagittal plane (P = 0.006), with CT showing a greater length in the
      coronal plane (P = 0.004). The equivalent dose in 2 Gy to 2.0 cm for the bladder
      was greater on CT than MRI (P = 0.041). The remainder of the dose volume
      histogram values for the OAR were similar between CT and MRI. With volume
      optimization, no significant differences were seen between HR-CTV dose parameters
      or doses to OAR. CONCLUSIONS: The CT- and MRI-based brachytherapy tissue
      delineation seems adequate for evaluation of OAR and target tissues, although the
      shapes of HR-CTV and OAR do differ. When adopting volume-based prescription,
      these differences may lead to altered target dosing. The clinical impact of these
      differences seems to be small and may demonstrate that planning with CT, if
      combined with one MRI, may be sufficient.

PMID- 20130503
TI  - Total vaginal necrosis: a representative example of underreporting severe late
      toxic reaction after concomitant chemoradiation for cervical cancer.
AB  - INTRODUCTION: There is paucity of information regarding a late toxic reaction
      after chemoradiation for locally advanced cervical cancer. We discuss this
      problem with special consideration to total vaginal necrosis (TVN), an
      underreported severe late complication of chemoradiation. METHODS: The records of
      98 cervical cancer patients who received chemoradiation at the Department of
      Oncology of the University College London Hospital between January 2004 and May
      2008 were reviewed. RESULTS: Eight women (8.2%) developed a severe late toxic
      reaction. From these, 3 patients (3.1% of the entire cohort and 37.5% of the
      patients with a severe late toxic reaction), who were 44 to 60 years old,
      developed a TVN 6 to 18 months after completion of chemoradiation. In all the TVN
      cases, surgical debridement was necessary to alleviate the symptoms. This was
      followed by an extensive period (up to 24 months) of consolidation. Heavy smoking
      (P = 0.022) was found to be a significant contributing factor for TVN.
      CONCLUSIONS: Total vaginal necrosis is an underreported but serious late
      complication after chemoradiation and leads to considerable chronic morbidity.
      Radiologic examinations and biopsies are required to exclude recurrent disease.
      Microvascular damage from radiation combined with heavy cigarette smoking is
      likely to be pivotal etiologic factors in the development of TVN. For
      radiotherapy-induced late toxic effects to step out of the gray area of oncologic
      literature, the clinical pictures should be reported in a more detailed manner.
      It might be a promising approach to work out a toxicity scale that combines the
      existing objectifiable grading systems with subjective quality-of-life
      assessments.

PMID- 20130504
TI  - Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the
      HYPER-O registry.
AB  - INTRODUCTION: An analysis of experience of surgical and gynecologic oncologists
      in the United States with the use of hyperthermic intraperitoneal chemotherapy
      for women with invasive epithelial ovarian cancer (EOC). METHODS: An Internet
      based registry (HYPER-O) collected data from collaborating institutions.
      Eligibility included women with EOC treated with hyperthermic intraperitoneal
      chemotherapy. Borderline and nonepithelial cancers were excluded. RESULTS: As of
      July 1, 2008, 141 women were eligible for analysis treated at the following time
      points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12),
      and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6
      degrees C (median, 41.9 degrees C) for inflow and 36.9 to 42.9 degrees C (median,
      41 degrees C) for outflow for 30 to 120 minutes. Treatment was with a platinum
      agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up
      was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months
      (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival
      probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110
      (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within
      30 days of surgery. In the multivariable analysis, the factors significant for
      increased survival were sensitivity to platinum response (P = 0.048),
      completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or
      a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of
      hospital stays of 10 days or less (P = 0.021). CONCLUSIONS: Hyperthermic
      intraperitoneal chemotherapy is a viable additional treatment option for patients
      with invasive EOC and may extend life in selected groups. It warrants further
      study in randomized controlled trials.

PMID- 20130505
TI  - Factors affecting the completion of intraperitoneal chemotherapy in women with
      ovarian cancer.
AB  - HYPOTHESIS: The use of intraperitoneal (IP) chemotherapy as treatment for ovarian
      cancer has been demonstrated to result in improved survival. However, it is
      associated with significant toxicity, resulting in the early discontinuation of
      therapy in many cases. This report quantifies and analyzes the reasons why
      patients discontinue therapy before completion and discusses strategies for
      improvement. METHODS: One hundred seventy-seven women with ovarian cancer who
      received IP chemotherapy for a 10-year period at a regional cancer center were
      followed, and demographic and treatment data were collected. SigmaStat (v2.0) was
      used to make statistical calculations regarding the data. RESULTS: One hundred
      seventy-seven subjects received 915 cycles of IP therapy. One hundred forty
      subjects received IP chemotherapy as initial treatment. Ninety-five (68%) of the
      140 subjects completed 6 planned cycles. Thirty-seven subjects received IP for
      recurrent disease. Only 14 (38%) of the 37 subjects completed 6 cycles (P =
      0.001). The most common reason for noncompletion of IP therapy was port occlusion
      (39/68 of the patients, 57%). Very few subjects refused treatment (9/68 of the
      patients, 13%). The rate of completion of therapy improved over time in this
      program (2001, 36%; 2009, 75%). CONCLUSIONS: The rate of completion of IP
      chemotherapy was higher in this institution than in other reports, including
      randomized multicenter trials. Port occlusion was the most common reason why IP
      chemotherapy was not completed. Subjective reasons for stopping therapy were
      rare. The establishment of a comprehensive, coordinated IP administration program
      is likely to result in improved completion rates. Completion rates within an
      institution improve with experience as well.

PMID- 20130506
TI  - Malignant transformation within ovarian dermoid cysts: an audit of treatment
      received and patient outcomes. an Australia New Zealand gynaecological oncology
      group (ANZGOG) and gynaecologic cancer intergroup (GCIG) study.
AB  - INTRODUCTION: Malignant transformation in an ovarian dermoid cyst occurs in 1% to
      2% of cases. Our knowledge about this tumor type is limited and largely based on
      case reports. We aimed to collate and analyze the cumulative experience of how
      these patients have been managed in an effort to identify the most appropriate
      treatment strategies. METHODS: A survey was sent to the members of the
      Gynaecologic Cancer Intergroup. Data collected included age, symptoms, stage,
      extent of surgery, chemotherapy and radiotherapy details, response to treatment,
      progression, survival, and salvage therapy. RESULTS: Data on 33 patients whose
      conditions were diagnosed between 1979 and 2007 were received from 10 centers in
      Australia, Canada, Germany, and Austria. The mean age was 49 years. All 15
      patients with stage I disease and most of the patients with stages II and III
      were optimally debulked. Four patients with stage I disease had fertility-sparing
      surgery with good outcomes. Chemotherapy was not routinely given after surgery
      and did not seem to be effective. Platinum-based regimens were most commonly
      used. At relapse, 2 patients had a sustained remission after secondary surgery
      for relapsed disease. Second-line chemotherapy and radiotherapy were infrequently
      prescribed. Patients with stage I disease had a good outcome, with all but 2
      alive and well at a minimum of 12 months of follow-up. CONCLUSIONS: Most patients
      undergo optimal debulking surgery. Fertility-sparing surgery may be a reasonable
      option in selected patients. Stage I patients have a good prognosis. There is no
      standard adjuvant treatment, but platinum-based regimens are most commonly used.
      However, regardless of treatment received, patients with advanced disease do
      poorly.

PMID- 20130507
TI  - CA-125 response patterns in patients with recurrent ovarian cancer treated with
      pegylated liposomal doxorubicin (PLD).
AB  - INTRODUCTION: : In recurrent ovarian cancer, CA-125 could be the only objective
      response criteria. This study analyzes response patterns regarding CA-125 in
      responders versus nonresponders and determines whether a specific cutoff value
      for CA-125 could predict clinical response, compared with response evaluation
      criteria in solid tumors, in patients receiving pegylated liposomal doxorubicin
      (PLD). METHODS: : Sixty-eight patients were identified, 78% were platinum
      resistant. Relative changes in CA-125 values were calculated, and response was
      defined as higher than 50% reduction in CA-125 from baseline. Receiver operating
      characteristic (ROC) curves were constructed based on CA-125 value after the
      first cycle of PLD to evaluate the most precise cutoff point for the decision
      model predicting response. RESULTS: : Fifty-three patients were assessable for
      response: 16 patients responded and 37 did not; the median increase of CA-125 was
      0.20 (-63; 312) and 52 (-29; 620), respectively. Our ROC curve generated a cutoff
      value with a sensitivity of 35% (positive test, the proportion of patients who
      will not respond) and a predictive positive value of 80%. According to the
      predictive positive value, 20% of the responder patients will be identified as
      nonresponders; P = 0.025. CONCLUSIONS: : Our ROC analysis did not demonstrate any
      reliable CA-125 cutoff on response. Discontinuation of the therapy before cycle 3
      may exclude some patients who will benefit from PLD.

PMID- 20130508
TI  - Expression of hCG and GnRHs and their receptors in endometrial carcinoma and
      hyperplasia.
AB  - OBJECTIVES: Recent studies propose the role of gonadotropins in the development
      and growth of endometrial carcinoma. The present research was undertaken to
      establish the expression of human chorionic gonadotropin (hCG), gonadotropin
      releasing hormones 1 (GnRH1 and GnRH2, respectively) and their receptors in
      endometrial hyperplasias and carcinoma. MATERIAL AND METHODS: The expression of
      analyzed genes in endometrial carcinoma and hyperplasia with and without atypia
      was evaluated using reverse transcriptase polymerase chain reaction and
      immunohistochemistry. RESULTS: The results of the experiments demonstrated the
      presence of hCG and GnRH1 at both messenger RNA and protein levels in endometrial
      carcinoma and atypical hyperplasia. Noncancerous tissue and hyperplasia without
      atypia demonstrated the lack of these gene coexpressions. The expression of
      GnRH2, LH/hCGR, and GnRHRs was heterogeneous, and the study molecules were found
      only in part of the analyzed tissues. The presence of hCG and GnRH1 and their
      receptors in cancer tissue and atypical hyperplasia suggests autocrine/paracrine
      action of hormones regulating the endometrial carcinoma cell proliferation.
      CONCLUSIONS: The interaction between the hCG and LH/hCGR in endometrial tissue
      might stimulate cell growth and promote neoangiogenesis, whereas GnRHs, by
      binding to their receptors, could be responsible for the antiproliferative effect
      and stimulation of apoptosis. The identification of differences in the expression
      profile of the analyzed genes could be relevant for better understanding of the
      development of endometrial carcinomas and could be useful in clinical
      diagnostics.

PMID- 20130509
TI  - Laparoscopy-assisted vaginal versus abdominal hysterectomy in endometrial cancer.
AB  - INTRODUCTION: The purpose of this study was to compare the efficacy of a
      laparoscopy-assisted surgical staging with a traditional laparotomy staging for
      the treatment of endometrial cancer. METHODS: We retrospectively analyzed the
      medical records of 465 patients with endometrial adenocarcinoma treated by
      surgery between January 1996 and December 2007. RESULTS: There were no
      significant differences between the laparoscopy and the laparotomy groups in age,
      body mass index, and histologic type. However, in the laparotomy group, grade and
      surgical stage were higher, the diseases were more chronic, and more
      postoperative adjuvant treatments were necessary. One hundred seven (76.4%) of
      140 patients in the laparoscopy group and 260 (80.0%) of the 325 patients in the
      laparotomy group had lymphadenectomy, and the median numbers of pelvic and
      paraaortic lymph nodes obtained were not statistically different. The laparoscopy
      group showed shorter postoperative hospital stay and lower blood loss, and the
      operating time was also shorter than that in the laparotomy group. There was no
      significant difference in intraoperative or postoperative complications, and the
      operative technique did not influence survival rates after adjusting several
      confounding factors. CONCLUSIONS: Our data of 12 years with a large number of
      patients show no differences in complications and impacts on survival between
      laparoscopy and laparotomy. Laparoscopy has advantages of shorter operating time
      and other advantages over laparotomy previously reported. Therefore, laparoscopy
      can be considered a good therapeutic option for endometrial cancer.

PMID- 20130510
TI  - The SUVmax of 18F-FDG PET correlates with histological grade in endometrial
      cancer.
AB  - OBJECTIVES: The objectives of this study were to assess the maximum standardized
      uptake value (SUVmax) of F-fluorodeoxyglucose (F-FDG) by a primary tumor of
      endometrial cancer with the use of positron emission tomography/computed
      tomography (PET/CT) and to assess its association with the clinical importance of
      the disease. METHODS: F-fluorodeoxyglucose PET/CT scan was performed on 44
      participants within 2 weeks before surgery. F-fluorodeoxyglucose uptake was
      quantified by calculating the SUVmax. The distribution of cases that scored
      positive for each of the biological parameters examined was correlated with the
      SUVmax of the F-FDG PET/CT and the glucose transporter-1 expression status
      obtained by immunohistochemistry. RESULTS: The mean SUVmax of the primary
      endometrial cancer tumors was 17.6 (range, 3.04-34.74). There were significant
      correlations between the SUVmax of the primary tumor and the International
      Federation of Gynecology and Obstetrics (FIGO) grade (P < 0.001), maximum tumor
      size (P < 0.001), and glucose transporter-1 expression (P < 0.001). Furthermore,
      multivariate analysis showed that the FIGO grade was most significantly
      identified as a relation factor of SUVmax (> or =17.6) for endometrial cancer (P
      = 0.017). The present findings indicate that a significant relationship was seen
      between the SUVmax and the FIGO grade in endometrial cancer. CONCLUSION: We
      propose that the primary tumor's SUVmax obtained from F-FDG PET/CT may be
      associated with aggressive biological characteristics in endometrial cancer.

PMID- 20130511
TI  - Ki-67 quantitative evaluation as a marker of cervical intraepithelial neoplasia
      and human papillomavirus infection.
AB  - OBJECTIVE: To assess the value of Ki-67 quantitative analysis in cervical
      intraepithelial neoplasia (CIN) in relation to CIN grading and human
      papillomavirus (HPV) group typing. METHODS: Cervical samples selected
      retrospectively from 106 cases were analyzed immunohistochemically for Ki-67
      positive nuclei in 3 epithelial layers and by polymerase chain reaction for HPV
      typing. RESULTS: The proportion of high-risk HPV positivity was 0% in normal
      controls and 30% in CIN 1, 57% in CIN 2, and 90% in CIN 3 groups, and there was
      no low-risk HPV finding in CIN 2 and CIN 3 cases (P < 0.001). High-risk HPV
      positive cases exhibited significantly more Ki-67-positive nuclei per 100-mum
      basal membrane, which were more frequent in the middle and upper third layers of
      the epithelium compared with low-risk HPV and HPV-negative cases (P < 0.001). The
      differences among the CIN groups in the total number and in the percentages of Ki
      67-positive nuclei in the lower, middle, and upper third layers of the epithelium
      were significant (P < 0.001). With the cutoff value of more than 33% Ki-67
      positive nuclei in the middle and the upper third layers of the epithelium, Ki-67
      staining demonstrated 98.4% sensitivity (60/61 cases) and 97.8% specificity
      (44/45 cases) for the detection of CIN 2/CIN 3 in our study group. CONCLUSIONS:
      The Ki-67 immunostaining proved to be predictive for high-risk HPV infection, and
      it can differentiate reactive lesions from cervical dysplasias. Ki-67
      quantitative analysis in 3 epithelial layers is a sensitive and specific method
      of differentiation between CIN 1 and CIN 2/CIN 3 grades and can be a valuable
      adjunctive method for more accurate CIN grading.

PMID- 20130512
TI  - Temozolomide in advanced and recurrent uterine leiomyosarcoma and correlation
      with o6-methylguanine DNA methyltransferase expression: a case series.
AB  - INTRODUCTION: Our objective was to retrospectively review temozolomide in
      advanced and recurrent uterine leiomyosarcoma and to determine if tumor O
      methylguanine DNA methyltransferase (MGMT) expression correlated with clinical
      response. METHODS: All patients with advanced or recurrent uterine leiomyosarcoma
      who received temozolomide during treatment were retrospectively identified.
      Relevant clinical and pathologic data were collected and compared. O
      Methylguanine DNA methyltransferase expression was assessed by
      immunohistochemistry and scored by a gynecologic pathologist blinded to clinical
      outcomes. RESULTS: From 1999 to 2008, 9 cases of leiomyosarcoma were diagnosed; 6
      patients received temozolomide. Median follow-up was 54 months (range, 4-114
      months). There was 1 patient with complete response, 1 durable partial response
      (27+ months), 3 stable disease (range, 3-10 months), and 1 progressive disease.
      Overall, 5 out of 6 patients derived clinical benefit. The patient with a
      complete response recurred 18 months after her last cycle. Median progression
      free interval was 15.4 months (95% confidence interval, 9.4-21.4). Two patients
      died of disease. Temozolomide was well tolerated with no dose-limiting
      toxicities, and no dose adjustments were required in 64 prescribed cycles. The
      MGMT expression was inversely correlated with response to temozolomide. Patients
      with tumors negative for MGMT expression had a median progression free interval
      of 18.5 months compared with 3 months for those whose tumors were positive,
      although not statistically significant. CONCLUSIONS: Temozolomide is an easily
      administered, well-tolerated chemotherapeutic option in advanced or recurrent
      uterine leiomyosarcomas with a reasonable response rate. Assessment of MGMT
      expression may identify a subset of patients that will respond optimally to this
      therapy.

PMID- 20130513
TI  - Human papillomavirus DNA presence in pelvic lymph nodes in cervical cancer.
AB  - INTRODUCTION: This work intends to present a systematic overview of data that
      have been published so far with regard to methods used for tissue sampling and
      DNA testing and with regard to the prevalence of human papillomavirus (HPV) DNA
      in pelvic lymph nodes (LNs) and its prognostic significance. METHODS: The HPV DNA
      status of LN in women with cervical cancer is being explored as a potential
      marker of "occult" metastases. Although the presence of HPV DNA in LN usually
      correlates with its metastatic involvement, there is always a subgroup of HPV
      positive but histologically negative LNs. RESULTS: The significance of HPV in
      negative LNs remains uncertain, although several studies have concluded that HPV
      is a risk factor of recurrence. CONCLUSIONS: A small group size and a short
      follow-up are the main limitations for drawing any conclusion concerning
      prognostic significance of the presence of HPV DNA in LNs.

PMID- 20130514
TI  - A phase II trial of less than 7 weeks of concomitant cisplatin-paclitaxel
      chemoradiation in locally advanced cervical cancer.
AB  - OBJECTIVES: This study was undertaken to determine the tolerability of a 7-week
      schedule of external beam radiation therapy, high-dose-rate brachytherapy, and
      weekly cisplatin and paclitaxel in patients with locally advanced carcinoma of
      the cervix. METHODS: Twenty-nine patients with International Federation of
      Gynecology and Obstetrics stages IB2 to IVa cervical cancer were treated with 40
      mg/m per week of intravenous (i.v.) cisplatin and 50 mg/m per week of i.v.
      paclitaxel combined with 45 Gy of pelvic external beam radiation therapy and 30
      Gy of high-dose-rate brachytherapy. RESULTS: Eleven patients (37.9%) were able to
      complete the 6 scheduled cycles of chemotherapy. The median number of weekly
      chemotherapy cycles administered was 5 (range, 2-7). Thirty-five (20.1%) of 174
      cycles of chemotherapy were not given because of toxicity. The median dose
      intensity of cisplatin was 31 mg/m per week (95% confidence interval [CI], 25.2
      36.8); that of paclitaxel was 44 mg/m per week (95% CI, 39.9-48.3). Twenty-two
      patients (78.6%) were able to complete the planned radiation course in less than
      7 weeks. Median radiation treatment length was 45 days (95% CI, 43.4-46.6). After
      a median follow-up of 48 months, 7 patients (24.1%) experienced severe (Radiation
      Therapy Oncology Group grade 3 or higher) late toxicity. No fatal events were
      observed. Seven patients have failed, 1 locally and 6 at distant sites. The 8
      year local/pelvic control rate was 95.7%, and the 8-year freedom from systemic
      failure rate was 76.1%. Eight-year actuarial disease-free survival and overall
      survival were 63.1% and 75.9%, respectively. CONCLUSIONS: This study demonstrated
      unacceptable toxicity of combining the stated doses of concurrent cisplatin and
      paclitaxel chemotherapy with definitive radiotherapy for patients with advanced
      cervical cancer. Additional phase I/II trials are recommended to clearly
      establish the recommended phase II dose for these drugs.

PMID- 20130515
TI  - Distribution of p53, GST, and MTHFR polymorphisms and risk of cervical
      intraepithelial lesions in sicily.
AB  - OBJECTIVES: Host factors, including genetic polymorphisms, may explain some of
      the individual differences in cervical cancer occurrence, and susceptibility
      information may be useful to address effective and specific preventive strategies
      for different countries. The purpose of the present study was to investigate the
      role of p53 codon 72, glutathione S-transferase class mu (GSTM1), glutathione S
      transferase class theta (GSTT1), and methylenetetrahydrofolate reductase (MTHFR)
      C677T polymorphisms on the risk for infection and/or of cervical intraepithelial
      lesions in women attending a colposcopy service in Catania, Sicily, with an
      already reported high prevalence of human papillomavirus. METHODS: To identify
      the association among individual genetic polymorphisms, human papillomavirus
      infection, and histological findings, a case-control study was designed.
      Furthermore, to assess the combined effects of these polymorphisms on cervical
      cancer risk, combined genotype frequencies were compared among case patients and
      controls. RESULTS: Women homozygous for the p53 codon 72 Arg genotype were at a
      5.6-fold higher risk for developing cervical intraepithelial neoplasia (CIN) 2 or
      3 compared with those showing homozygosity for the Pro genotype or heterozygosity
      for the Pro/Arg genotype. The GSTM1 and GSTT1 null genotypes were overrepresented
      in infected patients and in women with CIN 2 or 3, although without any
      significant associations. A decreased risk for CIN of individuals homozygous for
      the MTHFR T allele was shown. CONCLUSIONS: After multiple logistic analyses, the
      presence of the allele 677T of the MTHFR gene was the best explaining protective
      factor against cervical carcinogenesis, and the allelic distribution in the
      control group followed the Hardy-Weinberg equilibrium expectations. However, the
      findings of our study still remain to be confirmed by additional and larger
      population-based surveys.

PMID- 20130516
TI  - Prevalence and type distribution of human papillomavirus in women with cervical
      lesions in Liaoning Province, China.
AB  - INSTRUCTION: Type-specific persistence of human papillomavirus (HPV) infection
      can cause invasive cervical cancer. The distribution and prevalence of HPV
      genotypes depend on the geographic region and on demographic factors. METHODS:
      This study aimed to investigate the prevalence and distribution of HPV genotypes
      in uterine cervical lesions in Liaoning Province, China. A total of 1444 cervical
      swabs from patients with cervical cancer (CC, n = 134), cervical intraepithelial
      neoplasia (CIN) II/III (n = 517), and CIN I (n = 180) were detected for HPV
      genotypes using the PGMY09/11 primer system and HPV GenoArray test (HybriBio
      Ltd., Hong Kong). Age-matched samples of 613 women without cervical neoplasia
      were analyzed as control. RESULTS: The prevalence of HPV was 82.84% in CC, 89.56%
      in CIN II/III, 70.56% in CIN I, and 44.70% in control. The 5 leading genotypes in
      CIN II/III were, in descending order of prevalence, HPV types 16 (61.12%), 58
      (14.12%), 33 (13.93%), 31 (8.32%), and 52(6.27%); whereas HPV types 16 (73.13%),
      18 (7.46%), 58 (3.73%), and 31/33/39 (all were 2.24%) were in CC. Multiple HPV
      infections comprising 2 to 5 types were found in 17.59% of the patients. Human
      papillomavirus 16 was the predominant genotype in all categories. The prevalence
      of both HPV type 16 and single HPV infection increased with the severity of
      cervical lesions (P = 0.000). CONCLUSIONS: The efficacy of the prophylactic
      vaccine against types 16 and 18 for preventing cervical cancer would be close to
      80% in Liaoning Province, China. Human papillomavirus types 16, 18, 58, 33, and
      31 may be predominant high-risk factors for CC and its precursors in this region.

PMID- 20130517
TI  - High-risk HPV genotyping in the follow-up of women treated conservatively for
      microinvasive cervical cancer.
AB  - OBJECTIVES: Conservative management of women with microinvasive cervical cancer
      (International Federation of Gynecologists and Obstetricians stage IA) has led to
      prolonged and intensive cytological follow-up. We conducted a retrospective study
      to assess human papillomavirus status and genotypes at diagnosis and to find out
      whether there is an association between the persistence of high-risk human
      papillomavirus during follow-up and the detection of recurrent disease. STUDY
      DESIGN: Paraffin-embedded cervical biopsies in the pathology archives were
      identified from women with an initial large loop excision of the transformation
      zone or cone specimen diagnostic of microinvasive disease since 1991. RESULTS: We
      identified 45 women with a diagnosis of microinvasive cervical cancer. Human
      papillomavirus was detected in 87% of the initial diagnostic specimens. Human
      papillomavirus testing showed a negative predictive value of 100% for recurrent
      disease with a sensitivity of 100%. CONCLUSION: Human papillomavirus testing has
      an important role in the follow-up of women treated conservatively for stage IA
      cervical cancer.

PMID- 20130518
TI  - Indication of radiotherapy for women with cervical cancer in Rio De Janeiro,
      Brazil.
AB  - The objective of this article was to analyze the treatment modalities used at the
      Brazilian National Cancer Institute, with particular emphasis on the use of
      radiotherapy (RT) and its indications in invasive cervical cancer, considering
      the staging and clinical epidemiological characteristics of the population. All
      cases of primary invasive tumors of the cervix (CID C53) registered at the
      institute and diagnosed between 1999 and 2004 were selected. The following
      variables were studied: (1) age, (2) year of diagnosis, (3) level of schooling,
      (4) race, (5) histopathologic subtype, (6) the staging of the tumor on diagnosis,
      and (7) the treatment modality initially offered. We analyzed 3509 cases of
      invasive disease, and 79.7% of them received RT. Based on the final logistic
      model, it was possible to construct a probabilistic model for the indication of
      RT in the subgroups formed by the combinations of the 3 highlighted variables
      (stage, age, and histological type). The likelihood varied from 22.5% in those
      with epidermoid carcinoma, stage I, younger than 55 years up to 100% in those
      with locally advanced disease and older than 65 years. These results indicate the
      importance of RT as a modality of treatment of invasive cervical cancer in
      Brazil, where a substantial proportion of the diagnoses are made in advanced
      stages. This set of information regarding this important center may help the long
      term strategic planning and the allocation of funds that enable the high demand
      to be met in an optimized manner.

PMID- 20130519
TI  - Comparative study of laparoscopically assisted radical vaginal hysterectomy and
      open Wertheim-Meigs in patients with early-stage cervical cancer: eleven years of
      experience.
AB  - INTRODUCTION: The aim of this study was to compare the feasibility, safety, and
      survival outcomes of Coelio-Schauta (CS) procedure versus open Wertheim-Meigs
      (WM) as primary surgical treatment of early-stage cervical cancer. METHODS:
      Observational study on the consecutive cases of cervical cancer undergoing CS
      during the last 11 years at our institution was performed. Data on clinical
      characteristics of patients, surgical performance, long-term morbidity, and
      survival were prospectively analyzed and compared with a historical series of 23
      consecutive WM performed at the same hospital in the immediate previous period.
      RESULTS: Sixty-seven patients were included in the study group (CS). Cases and
      controls were comparable in age, body mass index, stage, tumor size, and
      histological diagnosis. The number of pelvic nodes, disease-free margin, and
      complications rate were similar in both groups, but blood loss and blood
      transfusion rate were marginally less in the CS group. Operating time was longer
      in the first 20 CS patients, but it became comparable to WM once the learning
      curve was overcome. Hospital stay was significantly shorter in the CS group as
      well as the bladder function recovery time. However, no differences were seen
      regarding long-term urinary and bowel function between groups. Four patients
      (5.9%) from the CS group and 3 (13%) in the WM group had recurrence. Mortality
      rates were 3% and 8.7%, respectively (P = not significant). CONCLUSIONS: The CS
      procedure is a suitable alternative to WM for small-volume, early-stage cervical
      cancer, showing a good safety profile, shorter postoperative recovery time, and
      similar survival outcomes.

PMID- 20130520
TI  - Polypropylene mesh implantation in combination with vacuum-assisted closure in
      the management of metastatic or locally recurrent vulvar cancer: case report and
      review of literature.
AB  - BACKGROUND: Mesh reconstruction, especially in combination with vacuum-assisted
      closure, might improve healing and reduce the surgical morbidity of extensive
      inguinofemoral lymphadenectomy or extensive local resection in progressive cancer
      of the vulva. CASES: Radical vulvectomy combined with inguinofemoral
      lymphadenectomy was performed in 2 patients (P1, P2). The inguinofemoral wound
      bed was stabilized by polypropylene mesh implantation and sealed with vacuum
      closure system. In 1 patient with local recurrence of vulvar cancer (P3), local
      excision and stabilization of the wound were performed by mesh implantation.
      CONCLUSIONS: Mesh implantation fulfills 2 purposes: (1) it protects exposed
      vessels and the wound can be vacuum sealed; and (2) it stabilizes the surgical
      bed, permitting the required radical excision locally and inside the vascular
      compartment.

PMID- 20130521
TI  - Robotic transperitoneal infrarenal aortic lymphadenectomy: technique and results.
AB  - INTRODUCTION: This study was designed to evaluate the feasibility and the results
      of robotic transperitoneal infrarenal aortic lymphadenectomy. METHODS:
      Development of a technique of robotic transperitoneal infrarenal aortic
      lymphadenectomy in female cadavers and review of the results in 33 patients who
      underwent the newly developed technique as part of the surgical treatment of
      gynecologic malignancies. RESULTS: The mean console time was 42 minutes (range,
      19-64 minutes). The mean number of nodes was 12.9 (range, 2-27); the mean number
      of positive nodes was 2.6 (range, 0-8). There was 1 conversion to laparotomy.
      CONCLUSIONS: Robotic transperitoneal infrarenal aortic lymphadenectomy can be
      performed adequately and safely with the robotic column at the patient's head.
      Operating table rotation and additional trocar sites are needed when used in
      conjunction with robotic pelvic surgery.

PMID- 20130522
TI  - Efficacy of a sodium hyaluronate-carboxycellulose membrane (seprafilm) for
      reducing the risk of early postoperative small bowel obstruction in patients with
      gynecologic malignancies.
AB  - OBJECTIVE: To evaluate the effect of a sodium hyaluronate and
      carboxymethylcellulose membrane (Seprafilm) on early postoperative small bowel
      obstruction (EPSBO) in patients with gynecologic malignancies. METHODS: One
      hundred forty-five patients who had Seprafilm placed during gynecological surgery
      between April 2002 and March 2007 (Seprafilm group) were compared with a
      historical control group of patients managed without Seprafilm between January
      1997 and March 2002. All patients undergoing primary surgery with pelvic or
      combined pelvic and para-aortic lymphadenectomy for gynecological malignancies
      were retrospectively assessed for EPSBO and surgical infections. RESULTS: The
      incidence of EPSBO was significantly lower (P < 0.05) in the Seprafilm group
      (3.1%, 6/191) than in the control group (13.9%, 25/180). According to logistic
      regression analysis, the use of Seprafilm (odds ratio, 0.18; 95% confidence
      interval, 0.07-0.47; P < 0.0005) and the performance of pelvic lymphadenectomy
      alone (odds ratio, 0.27; 95% confidence interval, 0.09-0.78; P < 0.02) were
      independent predictors of a lower rate of EPSBO. The incidence of surgical
      infection showed no significant difference between the Seprafilm group (3.6%) and
      the control group (6.7%). CONCLUSIONS: Placement of Seprafilm helped to prevent
      EPSBO and had no significant adverse effect on surgical infections in patients
      who underwent lymphadenectomy for gynecological malignancy.

PMID- 20130523
TI  - Improving the detection of illicit substance use in preoperative
      anesthesiological assessment.
AB  - AIM: Illicit substance use (ISU) is a worldwide burden, and its prevalence in
      surgical patients has not been well investigated. Co-consumption of legal
      substances, such as alcohol and tobacco, complicates the perioperative management
      and is frequently underestimated during routine preoperative assessment. The aim
      of this study was to compare the anesthesiologists' detection rate of ISU during
      routine preoperative assessment with a computerized self-assessment
      questionnaire. METHODS: In total, 2,938 patients were included in this study.
      Prior to preoperative assessment, patients were asked to complete a computer
      based questionnaire that addressed ISU, alcohol use disorder (AUDIT), nicotine
      use (Fagerstrom) and socio-economic variables (education, income, employment,
      partnership and size of household). Medical records were reviewed, and the
      anesthesiologists' detection of ISU was compared to the patients' self-reported
      ISU. RESULTS: Seven point five percent of patients reported ISU within the
      previous twelve months. ISU was highest in the age group between 18 and 30 years
      (26.4%; P<0.01). Patients reporting ISU were more often men than women (P<0.01),
      smokers (P<0.01) and tested positive for alcohol use disorder (P<0.01).
      Anesthesiologists detected ISU in one in 43 patients, whereas the computerized
      self-assessment reported it in one in 13 patients. The detection was best in the
      subgroup self-reporting frequent ISU (P<0.01). CONCLUSIONS: Anesthesiologists
      underestimate the prevalence of ISU. Computer-based self-assessment increases the
      detection of ISU in preoperative assessment and may decrease perioperative risk.
      More strategies to improve the detection of ISU as well as brief interventions
      for ISU are required in preoperative assessment clinics.

PMID- 20130524
TI  - Live imaging of cell motility and actin cytoskeleton of individual neurons and
      neural crest cells in zebrafish embryos.
AB  - The zebrafish is an ideal model for imaging cell behaviors during development in
      vivo. Zebrafish embryos are externally fertilized and thus easily accessible at
      all stages of development. Moreover, their optical clarity allows high resolution
      imaging of cell and molecular dynamics in the natural environment of the intact
      embryo. We are using a live imaging approach to analyze cell behaviors during
      neural crest cell migration and the outgrowth and guidance of neuronal axons.
      Live imaging is particularly useful for understanding mechanisms that regulate
      cell motility processes. To visualize details of cell motility, such as
      protrusive activity and molecular dynamics, it is advantageous to label
      individual cells. In zebrafish, plasmid DNA injection yields a transient mosaic
      expression pattern and offers distinct benefits over other cell labeling methods.
      For example, transgenic lines often label entire cell populations and thus may
      obscure visualization of the fine protrusions (or changes in molecular
      distribution) in a single cell. In addition, injection of DNA at the one-cell
      stage is less invasive and more precise than dye injections at later stages. Here
      we describe a method for labeling individual developing neurons or neural crest
      cells and imaging their behavior in vivo. We inject plasmid DNA into 1-cell stage
      embryos, which results in mosaic transgene expression. The vectors contain cell
      specific promoters that drive expression of a gene of interest in a subset of
      sensory neurons or neural crest cells. We provide examples of cells labeled with
      membrane targeted GFP or with a biosensor probe that allows visualization of F
      actin in living cells.

PMID- 20130525
TI  - Vitamin D deficiency and anemia in early chronic kidney disease.
AB  - Vitamin D has a number of pleiotropic effects in a variety of tissues, in
      addition to its well-known effects on mineral metabolism. To determine whether it
      has an effect on erythropoiesis, we studied the association of the components of
      the vitamin D axis with the prevalence and severity of anemia in chronic kidney
      disease. We measured the concentrations of 25-hydroxyvitamin D (25D), 1,25
      dihydroxyvitamin D (1,25D), and hemoglobin in a cross-sectional study of 1661
      subjects in SEEK, a multi-center cohort study of chronic kidney disease patients
      in the United States, of whom 41% met the criteria for anemia. The mean
      hemoglobin concentrations significantly decreased with decreasing tertiles of 25D
      and 1,25D. These linear trends remained significant after adjustment for age,
      gender, ethnicity, eGFR, diabetes, and parathyroid hormone. In similarly adjusted
      models, the lowest tertiles of 25D and 1,25D were independently associated with
      2.8- and 2.0-fold increased prevalence of anemia compared with their respective
      highest tertiles. Patients with severe dual deficiency of 25D and 1,25D had a 5.4
      fold prevalence of anemia compared with those replete in both. Our study shows
      that 25D and 1,25D deficiency are independently associated with decreased
      hemoglobin levels and anemia in chronic kidney disease. Whether this association
      is causal requires further study.

PMID- 20130526
TI  - p35, the non-cyclin activator of Cdk5, protects podocytes against apoptosis in
      vitro and in vivo.
AB  - Cyclin-dependent kinase-5 is widely expressed and predominantly regulated by the
      non-cyclin activator p35. Since we recently showed that expression of p35 in the
      kidney is restricted to podocytes, we examined here its function in mice in which
      p35 was genetically deleted. The mice did not exhibit kidney abnormalities during
      glomerular development or during adult life. Conditionally immortalized cultured
      podocytes, derived from these null mice, did not have any change in their
      morphology, differentiation, or proliferation. However, when these cultured
      podocytes were exposed to UV-C irradiation, serum depletion, puromycin
      aminonucleoside, or transforming growth factor-beta-1, they showed increased
      apoptosis compared to those from wild-type mice. Levels of Bcl-2 were decreased
      in these null podocytes but increased after transduction with human p35.
      Restoration of p35 or the ectopic expression of Bcl-2 reduced the susceptibility
      of p35-null podocytes to apoptosis. Experimental glomerulonephritis,
      characterized by podocyte apoptosis and subsequent crescent formation, was
      utilized to test these findings in vivo. Podocyte apoptosis was significantly
      increased in diseased p35-null compared with wild-type mice, accompanied by
      increased glomerulosclerosis and decreased renal function. Our study shows that
      p35 does not affect glomerulogenesis but controls podocyte survival following
      injury, in part, by regulating Bcl-2 expression.

PMID- 20130527
TI  - Higher systolic blood pressure is associated with progression of carotid intima
      media thickness in patients with chronic kidney disease.
AB  - To examine the relationship between systolic blood pressure and progression of
      carotid intima-media thickness in patients with chronic kidney disease (CKD), we
      studied 3364 patients from a community-based cohort of elderly individuals of
      whom 724 had CKD defined as creatinine clearances of stage 3 or less. The
      contribution of systolic blood pressure was evaluated in four ranges (<120, 120
      129, 130-139, and > or = 140 mm Hg). All multiple linear regression analyses were
      adjusted for traditional and nontraditional cardiovascular risk factors. The
      higher ranges of systolic blood pressure at baseline were associated with a
      greater carotid intima-media thickness at the initiation of the study in patients
      with or without CKD. Covariate-adjusted averages of carotid intima-media
      thickness at the initiation of the study in patients with CKD significantly
      increased across the four strata of systolic blood pressure. Higher systolic
      blood pressure at baseline was associated with a significantly greater yearly
      change in covariate-adjusted mean carotid intima-media thickness and vascular
      events in patients with CKD over a 4-year follow-up period.

PMID- 20130528
TI  - Toward the development of podocyte-specific drugs.
AB  - Most kidney diseases that ultimately lead to end-stage renal failure originate
      within the glomerulus and are associated with proteinuria. Treatment options are
      unspecific and offer partial cures at best because available therapies do not
      primarily treat glomerular cells but rather act systemically and thus cause many
      side effects. Most glomerulopathies directly stem from injury to podocytes, cells
      that have a key role in the maintenance of the glomerular filter. Thus, these
      cells constitute an obvious and promising target for the development of novel
      kidney-protective drugs. During the last decade, enormous advances have been made
      in the understanding of podocyte structure and function. A number of pathways
      that are altered during glomerular diseases may be targeted by novel small- and
      large-molecule drugs as well as biologicals that have been identified in
      nephrology and other areas of drug development. Cultured podocytes provide a
      valuable model for high-throughput drug screening assays. Furthermore, podocytes
      have been shown to possess many features that make them particularly good target
      cells for renal protection. This mini-review discusses some of the most recent
      promising data related to potential drug therapy for proteinuria and kidney
      disease through direct podocyte targeting.

PMID- 20130529
TI  - Hemodiafiltration: clinical evidence and remaining questions.
AB  - Currently, about two-thirds of hemodialysis patients worldwide are treated with
      high-flux membranes. This is most likely based on the assumption that the
      extended solute clearance that can be obtained with more open membranes will
      contribute to improved clinical outcome. To have full advantage of convective
      solute removal, hemodiafiltration offers a superior modality as compared to both
      low-flux and high-flux hemodialysis. However, this technique is offered to only a
      minority of patients. In this review, we summarize the available clinical
      evidence on hemodiafiltration and define still remaining questions.

PMID- 20130530
TI  - Critical role for osteopontin in diabetic nephropathy.
AB  - The profibrotic adhesion molecule, osteopontin (OPN), is upregulated in kidneys
      of humans and mice with diabetes. The thiazolidinedione (TZD) insulin sensitizers
      decrease albuminuria in diabetic nephropathy (DN) and reduce OPN expression in
      vascular and cardiac tissue. To examine whether OPN is a critical mediator of DN
      we treated db/db mice with insulin, rosiglitazone, or pioglitazone to achieve
      similar fasting plasma glucose levels. The urine albumin-to-creatinine ratio and
      glomerular OPN expression were increased in diabetic mice, but both were reduced
      by the TZDs more than by insulin. We administered streptozotocin to OPN-null and
      OPN-wild-type mice, and OPN-null mice were bred into both type 1 (Ins2(akita/+))
      and 2 (db/db) diabetic mice. In each case, OPN deletion decreased albuminuria,
      mesangial area, and glomerular collagen IV, fibronectin and transforming growth
      factor (TGF)-beta in the diabetic mice compared with their respective controls.
      In cultured mouse mesangial cells, TZDs but not insulin decreased angiotensin II
      induced OPN expression, while recombinant OPN upregulated TGF-beta, ERK/MAPK, and
      JNK/MAPK signaling. These studies show that OPN expression in DN mouse models
      enhances glomerular damage, likely through the expression of TGF-beta, while its
      deletion protects against disease progression, suggesting that OPN might serve as
      a therapeutic target.

PMID- 20130531
TI  - Recurrent membranoproliferative glomerulonephritis after kidney transplantation.
AB  - On examination of the records of 1321 patients following kidney transplant over
      an 11-year period, we found that 29 patients had recurrent membranoproliferative
      glomerulonephritis (MPGN). We excluded from this analysis patients who had MPGN
      type II, those with clear evidence of secondary MPGN, and those lacking post
      transplant biopsies. During an average of 53 months of follow-up, we found using
      protocol biopsies that 12 of these patients had recurrent MPGN diagnosed 1 week
      to 14 months post-transplant. In 4 of the 12 patients this presented clinically,
      whereas the remaining had subclinical disease. The risk of recurrence was
      significantly increased in patients with low complement levels. Serum monoclonal
      proteins were found in a total of six patients; appeared to be associated with
      earlier, more aggressive disease; and were more common in recurrent than non
      recurrent disease. The recurrence of MPGN was marginally higher in recipients of
      living-donor kidneys. Some patients developed characteristic lesions within 2
      months post-transplant, whereas others presented with minimal, atypical
      histological changes that progressed to MPGN. Of 29 patients, 5 lost their
      allograft and 2 patients remain on chronic plasmapheresis. Our study shows the
      risk of MPGN recurrence and progression depends on identifiable pretransplant
      characteristics, has variable clinical impact, and can result in graft failure.

PMID- 20130532
TI  - Tamm-Horsfall protein and urinary exosome isolation.
AB  - Urinary exosomes have been proposed as starting material for discovery of protein
      biomarkers of kidney disease. Current protocols for their isolation use a two
      step differential centrifugation process. Due to their low density, exosomes are
      expected to remain in the low-speed (17,000 x g) supernatant and to sediment only
      when the sample is spun at high speed (200,000 x g). Analysis using western blot
      and electron microscopy found that urinary exosomes are also present in the low
      speed pellet entrapped by polymeric Tamm-Horsfall protein, thus diminishing the
      procedure's reproducibility. Here we show that addition of dithiothreitol to the
      low-speed pellet disrupted the polymeric network, presumably by reduction of
      disulfide bonds linking the monomers. This modification shifted the exosomal
      proteins from the low- to the high-speed pellet. Also, by shifting the Tamm
      Horsfall protein to the high-speed pellet, the use of dithiothreitol makes it
      feasible to use Tamm-Horsfall protein to normalize excretion rates of exosomal
      proteins in spot urines. We tested this by western blot, and found that there was
      a high degree of correlation between exosomal proteins and Tamm-Horsfall protein
      in the high-speed pellet. Since the yield of exosomes by differential
      centrifugation can be increased by chemical reduction, Tamm-Horsfall protein may
      be a suitable normalizing variable for urinary exosome studies when quantitative
      urine collections are not practical.

PMID- 20130533
TI  - CRF-1 antagonist and CRF-2 agonist decrease binge-like ethanol drinking in
      C57BL/6J mice independent of the HPA axis.
AB  - Recent evidence suggests that corticotropin-releasing factor (CRF) receptor
      (CRFR) signaling is involved in modulating binge-like ethanol consumption in
      C57BL/6J mice. In this report, a series of experiments were performed to further
      characterize the role of CRFR signaling in binge-like ethanol consumption. The
      role of central CRFR signaling was assessed with intracerebroventricular (i.c.v.)
      infusion of the nonselective CRFR antagonist, alpha-helical CRF(9-41) (0, 1, 5,
      10 microg/1 microl). The contribution of central CRF type 2 receptor (CRF(2)R)
      signaling was assessed with i.c.v. infusion of the selective CRF(2)R agonist,
      urocortin (Ucn) 3 (0, 0.05, 0.1, or 0.5 microg/1 microl). The role of the
      hypothalamic-pituitary-adrenal (HPA) axis was assessed by pretreating mice with
      intraperitoneal (i.p.) injection of (1) the corticosterone synthesis inhibitor,
      metyrapone (0, 50, 100, 150 mg/kg) or (2) the glucocorticoid receptor antagonist,
      mifepristone (0, 25, 50 mg/kg), and (3) by using radioimmunoassay to determine
      whether binge-like ethanol intake influenced plasma corticosterone levels.
      Finally, we determined whether the ability of the CRF(1)R antagonist, CP-154,526
      (CP; 0, 10, 15 mg/kg, i.p.), to blunt binge-like drinking required normal HPA
      axis signaling by comparing the effectiveness of CP in adrenalectomized (ADX) and
      normal mice. Results showed that i.c.v. infusion of a 1 microg dose of alpha
      helical CRF(9-41) significantly attenuated binge-like ethanol consumption
      relative to vehicle treatment, and i.c.v. infusion of Ucn 3 dose-dependently
      blunted binge-like drinking. On the other hand, metyrapone nonselectively reduced
      both ethanol and sucrose consumption, mifepristone did not alter ethanol
      drinking, and binge-like drinking did not correlate with plasma corticosterone
      levels. Finally, i.p. injection of CP significantly attenuated binge-like ethanol
      intake in both ADX and normal mice. Together, these results suggest that binge
      like ethanol intake in C57BL/6J mice is modulated by CRF(1)R and CRF(2)R
      signaling, such that blockade of CRF(1)R or activation of CRF(2)R effectively
      reduces excessive ethanol intake. Furthermore, normal HPA axis signaling is not
      necessary to achieve binge-like drinking behavior.

PMID- 20130534
TI  - Changes in central sodium and not osmolarity or lactate induce panic-like
      responses in a model of panic disorder.
AB  - Panic disorder is a severe anxiety disorder characterized by recurrent panic
      attacks that can be consistently provoked with intravenous (i.v.) infusions of
      hypertonic (0.5 M) sodium lactate (NaLac), yet the mechanism/CNS site by which
      this stimulus triggers panic attacks is unclear. Chronic inhibition of GABAergic
      synthesis in the dorsomedial hypothalamus/perifornical region (DMH/PeF) of rats
      induces a vulnerability to panic-like responses after i.v. infusion of 0.5 M
      NaLac, providing an animal model of panic disorder. Using this panic model, we
      previously showed that inhibiting the anterior third ventricle region (A3Vr;
      containing the organum vasculosum lamina terminalis, the median preoptic nucleus,
      and anteroventral periventricular nucleus) attenuates cardiorespiratory and
      behavioral responses elicited by i.v. infusions of NaLac. In this study, we show
      that i.v. infusions of 0.5 M NaLac or sodium chloride, but not iso-osmolar D
      mannitol, increased 'anxiety' (decreased social interaction) behaviors, heart
      rate, and blood pressure responses. Using whole-cell patch-clamp preparations, we
      also show that bath applications of NaLac (positive control), but not lactic acid
      (lactate stimulus) or D-mannitol (osmolar stimulus), increases the firing rates
      of neurons in the A3Vr, which are retrogradely labeled from the DMH/PeF and which
      are most likely glutamatergic based on a separate study using retrograde tracing
      from the DMH/PeF in combination with in situ hybridization for vesicular
      glutamate transporter 2. These data show that hypertonic sodium, but not hyper
      osmolarity or changes in lactate, is the key stimulus that provokes panic attacks
      in panic disorder, and is consistent with human studies.

PMID- 20130535
TI  - Pergolide treatment of cognitive deficits associated with schizotypal personality
      disorder: continued evidence of the importance of the dopamine system in the
      schizophrenia spectrum.
AB  - Cognitive deficits observed in schizophrenia are also frequently found in
      individuals with other schizophrenia spectrum disorders, such as schizotypal
      personality disorder (SPD). Dopamine appears to be a particularly important
      modulator of cognitive processes such as those impaired in schizophrenia spectrum
      disorders. In a double-blind, placebo-controlled clinical trial, we administered
      pergolide, a dopamine agonist targeting D(1) and D(2) receptors, to 25
      participants with SPD and assessed the effect of pergolide treatment, as compared
      with placebo, on neuropsychological performance. We found that the pergolide
      group showed improvements in visual-spatial working memory, executive
      functioning, and verbal learning and memory. These results suggest that dopamine
      agonists may provide benefit for the cognitive abnormalities of schizophrenia
      spectrum disorders.

PMID- 20130537
TI  - Abstracts of the Annual Meeting of the United States and Canadian Academy of
      Pathology. March 20-26, 2010. Washington, DC, USA.

PMID- 20130536
TI  - Fibroblast growth factor-2 enhances extinction and reduces renewal of conditioned
      fear.
AB  - Anxiety disorders are increasingly prevalent in society; hence, there is a need
      to improve on existing treatments for such disorders. Fibroblast growth factor-2
      (FGF2), a mitogen that is involved in brain development and regeneration, has
      been shown to both facilitate long-term extinction of fear and reduce stress
      precipitated relapse in rats. Extinction is the laboratory analog of exposure
      based therapies in humans. In this study, we continued to investigate the
      clinical potential of FGF2 as a pharmacological enhancer of extinction by
      examining its effect on renewal, a common type of relapse. In all experiments,
      rats were trained to fear a white noise-conditioned stimulus, and then this
      learned fear was extinguished the following day. Rats received systemic
      injections of FGF2 or vehicle immediately after extinction training. At test, on
      the day after extinction training, levels of freezing elicited by the white noise
      in either the extinction context or the original training context were measured.
      FGF2-treated rats showed less renewal of fear when tested in the original
      training context than did vehicle-treated rats. This pattern occurred even when
      vehicle rats were given double the amount of extinction training, and when FGF2
      treated rats were given equivalent exposure to the extinction context. These
      results show that FGF2 facilitates long-term extinction and attenuates relapse,
      and thus highlight its potential as a novel pharmacological adjunct to exposure
      therapy.

PMID- 20130564
TI  - Lovastatin decreases acute mucosal inflammation via 15-epi-lipoxin A4.
AB  - The widespread use of statins for hypercholesterolemia has uncovered pleiotropic
      anti-inflammatory properties that were unexpected based on the drugs' original
      design; yet, mechanisms for these protective actions remain uncertain. In this
      study lovastatin triggered biosynthesis of the anti-inflammatory and pro
      resolving mediator 15-epi-lipoxin A(4) (15-epi-LXA(4)). During interactions
      between human neutrophils and airway epithelial cells, the statin-induced
      increase in 15-epi-LXA(4) was associated with increased 14,15-epoxyeicosatrienoic
      acid (14,15-EET) generation. When added to activated neutrophils, 14,15-EET
      enhanced 15-epi-LXA(4) biosynthesis. In a murine model of airway mucosal injury
      and inflammation, lovastatin increased 15-epi-LXA(4) formation in vivo and
      markedly decreased acute lung inflammation. Administration of 15-epi-LXA(4) also
      inhibited lung inflammation in an additive manner with lovastatin. Together,
      these results indicate that statin-triggered 15-epi-LXA(4) generation during
      human leukocyte-airway epithelial cell interactions is an endogenous mechanism
      for statin-mediated tissue protection at mucosal surfaces that may also be
      relevant in the statins' ability to stimulate the resolution of inflammation.

PMID- 20130565
TI  - Deconstructing the drug development process: the new face of innovation.

PMID- 20130566
TI  - Links between behavioral factors and inflammation.
AB  - This review focuses on the biobehavioral factors that show robust associations
      with markers of inflammation and discusses the following variables: diet,
      smoking, coffee, alcohol, exercise, and sleep disruption. Each of these variables
      has been assessed in large-scale epidemiological studies, and many of them have
      been assessed in clinical and experimental studies as well. Treatment strategies
      that target biobehavioral factors have the potential to complement and enhance
      the benefit of anti-inflammatory medicines.

PMID- 20130567
TI  - Trends in risks associated with new drug development: success rates for
      investigational drugs.
AB  - This study utilizes both public and private data sources to estimate clinical
      phase transition and clinical approval probabilities for drugs in the development
      pipelines of the 50 largest pharmaceutical firms (by sales). The study examined
      the development histories of these investigational compounds from the time point
      at which they first entered clinical testing (1993-2004) through June 2009. The
      clinical approval success rate in the United States was 16% for self-originated
      drugs (originating from the pharmaceutical company itself) during both the 1993
      1998 and the 1999-2004 subperiods. For all compounds (including licensed-in and
      licensed-out drugs in addition to self-originated drugs), the clinical approval
      success rate for the entire study period was 19%. The estimated clinical approval
      success rates and phase transition probabilities differed significantly by
      therapeutic class. The estimated clinical approval success rate for self
      originated compounds over the entire study period was 32% for large molecules and
      13% for small molecules. The estimated transition probabilities were also higher
      for all clinical phases with respect to large molecules.

PMID- 20130568
TI  - Proof of concept: a PhRMA position paper with recommendations for best practice.
AB  - Proof of concept (POC) may be defined as the earliest point in the drug
      development process at which the weight of evidence suggests that it is
      "reasonably likely" that the key attributes for success are present and the key
      causes of failure are absent. POC is multidimensional but is focused on
      attributes that, if not addressed, represent a threat to the success of the
      project in crucial areas such as safety, efficacy, pharmaceutics, and commercial
      and regulatory issues. The appropriate weight of evidence is assessed through the
      use of mathematical models and by evaluating the consequences of advancing a
      candidate drug that is not safe, effective, or commercially viable, vs. failing
      to advance a candidate that possesses these attributes. Tools for POC include
      biomarkers, targeted populations, pharmacokinetic (PK)/pharmacodynamic (PD)
      modeling, simulation, and adaptive study designs. Challenges to the success of
      POCs include a shortage of skilled personnel, failure to integrate multiple
      disciplines and information, and the demand made by organizations for certainty.

PMID- 20130569
TI  - ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol
      response to rosuvastatin.
AB  - The ATP-binding cassette G2 (ABCG2) c.421C>A (rs2231142) polymorphism influences
      the pharmacokinetics of rosuvastatin. We examined whether this polymorphism
      influences the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of
      the drug. In 305 Chinese patients with hypercholesterolemia who were treated with
      rosuvastatin at a dosage of 10 mg daily, the c.421A variant was found to be
      significantly associated with greater reduction in LDL-C level, in a gene-dose
      dependent manner. As compared with subjects with the c.421CC genotype, those with
      the c.421AA genotype showed a 6.9% greater reduction in LDL-C level, which would
      be equivalent to the effect obtained by doubling the dose of rosuvastatin.

PMID- 20130570
TI  - Cough in pediatric patients receiving angiotensin-converting enzyme inhibitor
      therapy or angiotensin receptor blocker therapy in randomized controlled trials.
AB  - The incidence of cough in children receiving antihypertension therapy with
      angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers
      (ARBs) is unknown. We analyzed patient-level data from eight randomized trials
      for the treatment of pediatric hypertension, six of them involving ACEis and two
      involving ARBs. The incidence of cough in children receiving ACEis (reported
      cough, 3.2%) was similar to that in children receiving ARBs (reported cough,
      1.8%) (P = 0.34). Reports of cough were lower in children than in adults.

PMID- 20130571
TI  - Scientific writing 101.
AB  - Less is more when it comes to writing a good scientific paper. Tell a story in
      clear, simple language and keep in mind the importance of the 'big picture'.

PMID- 20130572
TI  - Substrate check of gamma-secretase.

PMID- 20130573
TI  - Two ways to misregulate mRNAs in myotonic dystrophy.

PMID- 20130575
TI  - Odorant reception in the malaria mosquito Anopheles gambiae.
AB  - The mosquito Anopheles gambiae is the major vector of malaria in sub-Saharan
      Africa. It locates its human hosts primarily through olfaction, but little is
      known about the molecular basis of this process. Here we functionally
      characterize the Anopheles gambiae odorant receptor (AgOr) repertoire. We
      identify receptors that respond strongly to components of human odour and that
      may act in the process of human recognition. Some of these receptors are narrowly
      tuned, and some salient odorants elicit strong responses from only one or a few
      receptors, suggesting a central role for specific transmission channels in human
      host-seeking behaviour. This analysis of the Anopheles gambiae receptors permits
      a comparison with the corresponding Drosophila melanogaster odorant receptor
      repertoire. We find that odorants are differentially encoded by the two species
      in ways consistent with their ecological needs. Our analysis of the Anopheles
      gambiae repertoire identifies receptors that may be useful targets for
      controlling the transmission of malaria.

PMID- 20130576
TI  - RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance
      growth.
AB  - Activating mutations in KRAS and BRAF are found in more than 30% of all human
      tumours and 40% of melanoma, respectively, thus targeting this pathway could have
      broad therapeutic effects. Small molecule ATP-competitive RAF kinase inhibitors
      have potent antitumour effects on mutant BRAF(V600E) tumours but, in contrast to
      mitogen-activated protein kinase kinase (MEK) inhibitors, are not potent against
      RAS mutant tumour models, despite RAF functioning as a key effector downstream of
      RAS and upstream of MEK. Here we show that ATP-competitive RAF inhibitors have
      two opposing mechanisms of action depending on the cellular context. In
      BRAF(V600E) tumours, RAF inhibitors effectively block the mitogen-activated
      protein kinase (MAPK) signalling pathway and decrease tumour growth. Notably, in
      KRAS mutant and RAS/RAF wild-type tumours, RAF inhibitors activate the RAF-MEK
      ERK pathway in a RAS-dependent manner, thus enhancing tumour growth in some
      xenograft models. Inhibitor binding activates wild-type RAF isoforms by inducing
      dimerization, membrane localization and interaction with RAS-GTP. These events
      occur independently of kinase inhibition and are, instead, linked to direct
      conformational effects of inhibitors on the RAF kinase domain. On the basis of
      these findings, we demonstrate that ATP-competitive kinase inhibitors can have
      opposing functions as inhibitors or activators of signalling pathways, depending
      on the cellular context. Furthermore, this work provides new insights into the
      therapeutic use of ATP-competitive RAF inhibitors.

PMID- 20130578
TI  - Evidence based spinal cord medicine.

PMID- 20130577
TI  - CHD7 cooperates with PBAF to control multipotent neural crest formation.
AB  - Heterozygous mutations in the gene encoding the CHD (chromodomain helicase DNA
      binding domain) member CHD7, an ATP-dependent chromatin remodeller homologous to
      the Drosophila trithorax-group protein Kismet, result in a complex constellation
      of congenital anomalies called CHARGE syndrome, which is a sporadic, autosomal
      dominant disorder characterized by malformations of the craniofacial structures,
      peripheral nervous system, ears, eyes and heart. Although it was postulated 25
      years ago that CHARGE syndrome results from the abnormal development of the
      neural crest, this hypothesis remained untested. Here we show that, in both
      humans and Xenopus, CHD7 is essential for the formation of multipotent migratory
      neural crest (NC), a transient cell population that is ectodermal in origin but
      undergoes a major transcriptional reprogramming event to acquire a remarkably
      broad differentiation potential and ability to migrate throughout the body,
      giving rise to craniofacial bones and cartilages, the peripheral nervous system,
      pigmentation and cardiac structures. We demonstrate that CHD7 is essential for
      activation of the NC transcriptional circuitry, including Sox9, Twist and Slug.
      In Xenopus embryos, knockdown of Chd7 or overexpression of its catalytically
      inactive form recapitulates all major features of CHARGE syndrome. In human NC
      cells CHD7 associates with PBAF (polybromo- and BRG1-associated factor-containing
      complex) and both remodellers occupy a NC-specific distal SOX9 enhancer and a
      conserved genomic element located upstream of the TWIST1 gene. Consistently,
      during embryogenesis CHD7 and PBAF cooperate to promote NC gene expression and
      cell migration. Our work identifies an evolutionarily conserved role for CHD7 in
      orchestrating NC gene expression programs, provides insights into the synergistic
      control of distal elements by chromatin remodellers, illuminates the patho
      embryology of CHARGE syndrome, and suggests a broader function for CHD7 in the
      regulation of cell motility.

PMID- 20130582
TI  - Nanofood for thought.

PMID- 20130583
TI  - Nanotechnology in fertilizers.

PMID- 20130584
TI  - Nanomaterials and regulation of cosmetics.

PMID- 20130586
TI  - Single-molecule detection: focusing on the objective.

PMID- 20130587
TI  - Nanoelectronics: single dopants learn their place.

PMID- 20130588
TI  - Probe microscopy: images from below the surface.

PMID- 20130589
TI  - Carbon nanotubes: growth potential.

PMID- 20130590
TI  - Expression of the orphan protein Plet-1 during trichilemmal differentiation of
      anagen hair follicles.
AB  - The rat mAb 33A10 recognizes an antigen in a variety of mouse epithelial tissues.
      In this study, we investigated in detail the expression pattern of the 33A10
      defined antigen in the hair follicle. We show that 33A10 reactivity is confined
      to the most differentiated keratinocytes of the outer root sheath (ORS), the
      companion layer (CL), and to cells of the sebaceous gland duct. In vitro, the
      33A10-defined antigen is expressed in keratinocytes derived from the ORS and
      accumulates on induction of differentiation. Using microarray analysis and
      transient transfection approaches, we established that the 33A10-defined antigen
      is the orphan protein, Placenta-expressed transcript (Plet)-1. Biochemical data
      indicated that Plet-1 is a glycosylphosphatidylinositol-anchored glycoprotein
      with N-linked carbohydrates in addition to other posttranslational modifications.
      Although silencing of Plet-1 expression using stable RNA interference in ORS
      keratinocytes decreased cellular migration, it increased adhesion to collagens I
      and IV. Immunohistochemical analysis showed that Plet-1 was primarily localized
      at the leading edge of epidermal wounds, where keratinocytes contacted the
      eschar. The restricted localization in both differentiated ORS and CL cells
      contacting the hair fiber and epidermal wounds suggests a role for the Plet-1
      protein in regulating the interaction of keratinocytes with inert tissues.

PMID- 20130591
TI  - Infrared A radiation influences the skin fibroblast transcriptome: mechanisms and
      consequences.
AB  - Infrared A (IRA) radiation (760-1440 nm) is a major component of solar radiation
      and, similar to UVR, causes photoaging of human skin by increasing the expression
      of matrix metalloproteinase-1 in human skin fibroblasts. In this study, we
      assessed the IRA-induced transcriptome in primary human skin fibroblasts.
      Microarray analysis revealed 599 IRA-regulated transcripts. The IRA-induced
      transcriptome differed from changes known to be induced by UV. IRA-responsive
      genes include the categories extracellular matrix, calcium homeostasis, stress
      signaling, and apoptosis. Selected results were confirmed by real-time PCR
      experiments analyzing 13 genes representing these four categories. By means of
      chemical inhibitors of known signaling pathways, we showed that ERK1/2, the p38-,
      JNK-, PI3K/AKT-, STAT3-, and IL-6 as well as the calcium-mediated signaling
      pathways, are functionally involved in the IRA gene response and that a major
      part of it is triggered by mitochondrial and, to a lesser extent, non
      mitochondrial production of reactive oxygen species. Our results identify IRA as
      an environmental factor with relevance for skin homeostasis and photoaging.

PMID- 20130592
TI  - Homozygous mutations in the 5' region of the JUP gene result in cutaneous disease
      but normal heart development in children.
AB  - Desmosomes are intercellular adhesive junctions and attachment sites for the
      intermediate filament (IF) cytoskeleton, prominent in tissues subject to high
      levels of mechanical stress such as the epidermis and heart. The obligate
      desmosomal constituent, plakoglobin (PG), is involved in coupling transmembrane
      desmosomal components with IFs. PG also contributes to intercellular adhesion
      through adherens junctions and has additional signaling roles. To date, two
      mutations in the gene encoding PG, JUP, have been described, and in both
      instances, patients harboring pathogenic mutations suffered from arrhythmogenic
      right ventricular cardiomyopathy with or without skin abnormalities. We describe
      homozygous nonsense mutation, p.S24X, and homozygous splice site mutation,
      c.468G>A, in the JUP gene that results in skin fragility, diffuse palmoplantar
      keratoderma, and woolly hair with no symptoms of cardiomyopathy. We show barely
      detectable levels of PG immunostaining in skin sections from patients harboring
      these mutations and show that an alternative AUG codon in p.S24X mRNA translates
      a 42-amino-acid N-terminal truncation. We conclude that PG is required for
      correct maintenance of skin integrity, and the absence of heart phenotype in
      patients suggests that aberrant PG expression does not compromise normal human
      heart development in children. Our findings provide new insight into the distinct
      roles that PG has in the epidermis and heart.

PMID- 20130593
TI  - Genome-wide analysis of cutaneous T-cell lymphomas identifies three clinically
      relevant classes.
AB  - This study was undertaken to identify recurrent genetic alterations of the three
      main types of cutaneous T-cell lymphomas (CTCLs): mycosis fungoides (MF), Sezary
      syndrome (SS), and cutaneous anaplastic large-cell lymphoma (CALCL). Using array
      based comparative genomic hybridization, the molecular cytogenetic profiles of 72
      samples obtained from 58 patients with CTCL corresponding to 24 transformed MF (T
      MF), 16 SS, and 18 CALCLs were determined. T-MF was characterized by gains of
      1q25-31, 7p22-11.2, 7q21, 7q31, and 17q12, and losses of 9p21, 10p11.2, and
      10q26. SS exhibited gains of 8q23-24.3 and 17q23-24, as well as losses of 9p21,
      10p12-11.2, 10q22-24, 10q25-26, and 17p13-q11.1. Finally, CALCL exhibited 6q27
      and 13q34 losses. Such imbalances were statistically associated with one CTCL
      subtype. Unsupervised hierarchical clustering defined three categories of
      clinical relevance: (1) CALCL apart from epidermotropic-CTCL, (2) an SS-only
      category, and (3) a mixed category with T-MF and SS cases, with both primary and
      secondary SS cases. In rare cases, the genetic classification did not correspond
      to the inclusion diagnosis, possibly reflecting the association of two diseases
      in the same patient or initial misdiagnosis according to follow-up. Finally,
      different samples in the same patient clustered together, showing reproducibility
      of such a classifier.

PMID- 20130594
TI  - Soluble adenylyl cyclase defines a nuclear cAMP microdomain in keratinocyte
      hyperproliferative skin diseases.
AB  - Cyclic adenosine monophosphate (cAMP) is a nearly ubiquitous signaling molecule
      important for numerous signaling pathways in human skin. We studied a novel class
      of mammalian adenylyl cyclase, the soluble adenylyl cyclase (sAC). We examined
      sAC localization in normal human skin and found it to be present in
      keratinocytes, melanocytes, mononuclear cells, eccrine ducts, and nerves. In
      normal skin, sAC keratinocyte staining was evenly distributed throughout the
      cell. However, in certain hyperproliferative disorders of the skin, including
      psoriasis, verruca vulgaris, and SCCIS on sun-damaged skin, sAC keratinocyte
      staining was predominantly nuclear. In contrast, in other hyperproliferative
      disorders, such as basal cell carcinoma, sAC staining was similar to normal human
      skin. Using a model of epithelial differentiation, we established that sAC
      migrates into the nucleus when differentiated cells are induced to reenter the
      cell cycle. Previous work had determined that nuclear sAC activates the cAMP
      response-element-binding (CREB) transcription factor, and we found that in
      psoriasis lesions, nuclear sAC occurs concomitantly with activation of CREB.
      Hence, sAC may play a role in the pathogenesis of certain hyperproliferative skin
      disorders via modulation of gene expression.

PMID- 20130595
TI  - Deficient SOCS3 and SHP-1 expression in psoriatic T cells.
AB  - IFN-alpha and skin-infiltrating activated T lymphocytes have important roles in
      the pathogenesis of psoriasis. T cells from psoriatic patients display an
      increased sensitivity to IFN-alpha, but the pathological mechanisms behind the
      hyperresponsiveness to IFN-alpha remained unknown. In this study, we show that
      psoriatic T cells display deficient expression of the suppressor of cytokine
      signaling (SOCS)3 in response to IFN-alpha and a low baseline expression of the
      SH2-domain-containing protein-tyrosine phosphatase (SHP)-1 when compared with
      skin T cells from nonpsoriatic donors. Moreover, IFN-alpha-stimulated psoriatic T
      cells show enhanced activation of JAKs (JAK1 and TYK2) and signal transducers and
      activators of transcription. Increased expression of SOCS3 proteins resulting
      from proteasomal blockade partially inhibits IFN-alpha response. Similarly,
      forced expression of SOCS3 and SHP-1 inhibits IFN-alpha signaling in psoriatic T
      cells. In conclusion, our data suggest that loss of regulatory control is
      involved in the aberrant hypersensitivity of psoriatic T cells to IFN-alpha.

PMID- 20130596
TI  - Pheochromocytoma-related 'classic' takotsubo cardiomyopathy.
AB  - We report a case of a 53-year-old hypertensive male with takotsubo cardiomyopathy
      in the setting of pheochromocytoma. Pheochromocytoma presenting as takotsubo
      cardiomyopathy is a recognized but uncommon occurrence with recently increasing
      number of published cases. We present typical apical ballooning syndrome, with
      transient left ventricular apical ballooning in contrast to several reports, in
      which patients with pheochromocytoma-induced cardiomyopathy had so called
      'inverted'takotsubo cardiomyopathy. In patients being diagnosed with acute
      coronary syndrome symptoms without coronary artery stenosis or spasm, and
      pronounced blood pressure variability, pheochromocytoma-induced takotsubo or
      'inverted' takotsubo cardiomyopathy should be kept in mind.

PMID- 20130597
TI  - Managing hypertension in the very elderly: effect of adverse drug reactions
      (ADRs) on achieving targets.
AB  - The Hypertension in the Very Elderly trial (HYVET), demonstrated the benefit of
      antihypertensive treatment in patients >or=80 years. However, patients in this
      age group are at increased risk of drug interactions and adverse effects. We
      conducted a retrospective cohort study, in hypertensive patients aged >or=80
      years, to determine whether it is possible to follow the HYVET guidelines in an
      everyday clinical setting. We identified 100 patients aged >or=80 years referred
      to the Hypertension Clinic, University Hospital Birmingham, over a 10-year
      period. Most patients were referred to the clinic because of poorly controlled
      blood pressure despite treatment and all had 24 h ambulatory blood pressure
      monitoring (ABPM) as part of their assessment. All patients tolerated ABPM, and a
      'white coat' effect was demonstrated in 33 patients. In 64 out of 100 patients
      (57 on treatment), the ABPM confirmed poor blood pressure control. Despite this,
      26 of these patients had an antihypertensive either stopped (15), and /or reduced
      (3) or left unchanged (9) at clinic because of documented adverse drug reactions
      (ADRs). In 36 out of 100 patients, no additional antihypertensive therapy was
      needed because the blood pressure was either well-controlled on treatment (28),
      over-treated (4), or normotensive with a white coat effect (4). Despite this,
      antihypertensive agents were either stopped (10), and or reduced (5) because of
      ADRs in half the patients (14) from the well-controlled group. In conclusion, 40%
      patients had documented ADRs overall which limited further intervention,
      suggesting that implementation of the HYVET recommendations in clinical practice
      may be difficult.

PMID- 20130598
TI  - Blocking cytokine signaling along with intense Bcr-Abl kinase inhibition induces
      apoptosis in primary CML progenitors.
AB  - In chronic myeloid leukemia (CML) cell lines, brief exposure to pharmacologically
      relevant dasatinib concentrations results in apoptosis. In this study, we assess
      the impact of intensity and duration of Bcr-Abl kinase inhibition on primary
      CD34(+) progenitors of chronic phase CML patients. As CML cells exposed to
      dasatinib in vivo are in a cytokine-rich environment, we also assessed the effect
      of cytokines (six growth factors cocktail or granulocyte-macrophage colony
      stimulating factor (CSF) or granulocyte-CSF) in combination with dasatinib. In
      the presence of cytokines, short-term intense Bcr-Abl kinase inhibition (>or=90%
      p-Crkl inhibition) with 100 nM dasatinib did not reduce CD34(+) colony-forming
      cells (CFCs). In contrast, without cytokines, short-term exposure to dasatinib
      reduced CML-CD34(+) CFCs by 70-80%. When cytokines were added immediately after
      short-term exposure to dasatinib, CML-CD34(+) cells remained viable, suggesting
      that oncogene dependence of these cells can be overcome by concomitant or
      subsequent exposure to cytokines. Additional inhibition of Janus tyrosine kinase
      (Jak) activity re-established the sensitivity of CML progenitors to intense Bcr
      Abl kinase inhibition despite the presence of cytokines. These findings support
      the contention that therapeutic strategies combining intense Bcr-Abl kinase
      inhibition and blockade of cytokine signaling pathways can be effective for
      eradication of CML progenitors.

PMID- 20130599
TI  - NF-kappaB activation mediates resistance to IFN beta in MLL-rearranged acute
      lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) harboring the t(4;11) translocation is
      associated with a very poor prognosis; innovative treatment strategies are
      required to improve the current 5-year survival rate of 30-40%. Interferon beta
      (IFN beta) has shown promise in the treatment of both solid and hematologic
      malignancies, although the short half-life and toxicity associated with high
      doses have limited its clinical utility. To overcome these limitations, we
      investigated the effect of continuous, gene transfer-mediated delivery of IFN
      beta using adeno-associated virus (AAV)-mediated expression, on ALL cells with
      the t(4;11) translocation. We found that this method of IFN beta delivery
      resulted in complete remission of leukemia in a murine model. However, leukemic
      cells eventually became resistant to IFN beta and relapse was observed.
      Activation of NF-kappaB was identified as a mechanism for IFN beta resistance,
      and inhibition of NF-kappaB activity in resistant cells sensitized cells to IFN
      beta. IFN beta combined with agents that inhibit NF-kappaB could have therapeutic
      potential in the treatment of children with mixed lineage leukemia subtype ALL.

PMID- 20130600
TI  - Lenalidomide induces cell death in an MDS-derived cell line with deletion of
      chromosome 5q by inhibition of cytokinesis.
AB  - Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders
      characterized by refractory cytopenias and susceptibility to leukemic
      transformation. On a subset of MDS patients with deletion of the long arm of
      chromosome 5 (del(5q)), lenalidomide exerts hematological and cytogenetic
      effects, but the underlying pharmacological mechanisms are not fully understood.
      In this study, we have investigated the in vitro effects of lenalidomide on an
      MDS-derived cell line, MDS-L, which carries del(5q) and complex chromosome
      abnormalities. We found that the growth of MDS-L cells was specifically
      suppressed mainly by apoptosis, and in addition, multinucleated cells were
      frequently formed and finally died out in the presence of lenalidomide. Time
      lapse microscopic observation and the DNA ploidy analysis revealed that
      lenalidomide does not affect DNA synthesis but inhibits cytokinesis of MDS-L
      cells. The gene expression profile showed decreased expression of M phase-related
      genes such as non-muscle myosin heavy-chain 10, polo-like kinase 1, aurora kinase
      B, citron kinase and kinesin family member 20A(KIF20A). Interestingly, KIF20A is
      located at 5q31. These data contribute to the understanding of action mechanisms
      of lenalidomide on MDS with del(5q) and complex abnormalities.

PMID- 20130601
TI  - Leukocytosis is associated with poor survival but not with increased risk of
      thrombosis in essential thrombocythemia: a population-based study of 311
      patients.

PMID- 20130602
TI  - gammaH2AX: a sensitive molecular marker of DNA damage and repair.
AB  - Phosphorylation of the Ser-139 residue of the histone variant H2AX, forming
      gammaH2AX, is an early cellular response to the induction of DNA double-strand
      breaks. Detection of this phosphorylation event has emerged as a highly specific
      and sensitive molecular marker for monitoring DNA damage initiation and
      resolution. Further, analysis of gammaH2AX foci has numerous other applications
      including, but not limited to, cancer and aging research. Quantitation of
      gammaH2AX foci has also been applied as a useful tool for the evaluation of the
      efficacy of various developmental drugs, particularly, radiation modifying
      compounds. This review focuses on the current status of gammaH2AX as a marker of
      DNA damage and repair in the context of ionizing radiation. Although the emphasis
      is on gamma-radiation-induced gammaH2AX foci, the effects of other genotoxic
      insults including exposure to ultraviolet rays, oxidative stress and chemical
      agents are also discussed.

PMID- 20130603
TI  - The degree of myelosuppression during maintenance therapy of adolescents with B
      lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse.
AB  - Drug doses, blood levels of drug metabolites and myelotoxicity during 6
      mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59
      adolescents (>or=10 years) and 176 non-adolescents (<10 years) with B-cell
      precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC)
      <50 x 10(9)/l at diagnosis. Event-free survival was lower for adolescents than
      non-adolescents (pEFS(12y):0.71 vs 0.83, P=0.04). For adolescents staying in
      remission, the mean WBC during maintenance therapy (mWBC) was related to age
      (r(S)=0.36, P=0.02), which became nonsignificant for those who relapsed
      (r(S)=0.05, P=0.9). The best-fit multivariate Cox regression model to predict
      risk of relapse included mWBC and thiopurine methyltransferase activity, which
      methylates mercaptopurine and reduces the intracellular availability of cytotoxic
      6-thioguanine nucleotides (coefficient: 0.11, P=0.02). The correlation of mWBC to
      the risk of relapse was more pronounced for adolescents (coefficient=0.65,
      P=0.003) than for non-adolescents (coefficient=0.42, P=0.04). Adolescents had
      higher mean neutrophil counts (P=0.002) than non-adolescents, but received
      nonsignificantly lower mercaptopurine and MTX doses during maintenance therapy.
      Red blood cell MTX levels were significantly related to the dose of MTX among
      adolescents who stayed in remission (r(S)=0.38, P=0.02), which was not the case
      for those who developed a relapse (r(S)=0.15, P=0.60). Thus, compliance to
      maintenance therapy may influence the risk of relapse for adolescents with ALL.

PMID- 20130607
TI  - Time for the epigenome.

PMID- 20130608
TI  - Stand and deliver.

PMID- 20130609
TI  - Back to books.

PMID- 20130615
TI  - Journal club. A bioengineer discusses how mechanical forces in tissues may
      promote malignancy.

PMID- 20130620
TI  - Obama budget backs basic science.

PMID- 20130621
TI  - IPCC flooded by criticism.

PMID- 20130622
TI  - Biodiversity law could stymie research.

PMID- 20130623
TI  - America pushes to overhaul chemical safety law.

PMID- 20130624
TI  - Mars rover Spirit (2003-10).

PMID- 20130625
TI  - Networking: Four ways to reinvent the Internet.

PMID- 20130626
TI  - Chemistry: Breaking the billion-hertz barrier.

PMID- 20130627
TI  - Better all the time.

PMID- 20130628
TI  - Women: diversity among leaders is there if you look.

PMID- 20130629
TI  - Could a boom in technologies trap Feynman's simulator?

PMID- 20130630
TI  - Women: why just one to represent half the workforce?

PMID- 20130631
TI  - Expanded view of universities would be more realistic.

PMID- 20130632
TI  - Political instability may be a contributor in the coming decade.

PMID- 20130635
TI  - Q&A: Peter Atkins on writing textbooks. Interview by Nicola Jones.

PMID- 20130636
TI  - Biogeography: Washed up in Madagascar.

PMID- 20130637
TI  - Photosynthesis: Quantum design for a light trap.

PMID- 20130638
TI  - Stem cells: Big roles for small RNAs.

PMID- 20130640
TI  - Extrasolar planets: Fluorescent methane spotted.

PMID- 20130641
TI  - Biomaterials: Dew catchers.

PMID- 20130642
TI  - Applied physics: Nanothermal trumpets.

PMID- 20130643
TI  - An aspartyl protease directs malaria effector proteins to the host cell.
AB  - Plasmodium falciparum causes the virulent form of malaria and disease
      manifestations are linked to growth inside infected erythrocytes. To survive and
      evade host responses the parasite remodels the erythrocyte by exporting several
      hundred effector proteins beyond the surrounding parasitophorous vacuole
      membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that
      is a substrate for an unknown protease. Here we show that the protein responsible
      for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease
      located in the endoplasmic reticulum. PMV cleavage reveals the export signal
      (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical
      mature protein with xQ at the N terminus generated by signal peptidase was not
      exported, demonstrating that PMV activity is essential and linked with other key
      export events. Identification of the protease responsible for export into
      erythrocytes provides a novel target for therapeutic intervention against this
      devastating disease.

PMID- 20130644
TI  - Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte.
AB  - During their intraerythrocytic development, malaria parasites export hundreds of
      proteins to remodel their host cell. Nutrient acquisition, cytoadherence and
      antigenic variation are among the key virulence functions effected by this
      erythrocyte takeover. Proteins destined for export are synthesized in the
      endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows
      translocation into the host cell via an ATP-driven translocon called the PTEX
      complex. We report that plasmepsin V, an ER aspartic protease with distant
      homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and
      cleaves it at the correct site. This enzyme is essential for parasite viability
      and ER residence is essential for its function. We propose that plasmepsin V is
      the PEXEL protease and is an attractive enzyme for antimalarial drug development.

PMID- 20130645
TI  - A ground-based near-infrared emission spectrum of the exoplanet HD 189733b.
AB  - Detection of molecules using infrared spectroscopy probes the conditions and
      compositions of exoplanet atmospheres. Water (H(2)O), methane (CH(4)), carbon
      dioxide (CO(2)), and carbon monoxide (CO) have been detected in two hot Jupiters.
      These previous results relied on space-based telescopes that do not provide
      spectroscopic capability in the 2.4-5.2 microm spectral region. Here we report
      ground-based observations of the dayside emission spectrum for HD 189733b between
      2.0-2.4 microm and 3.1-4.1 microm, where we find a bright emission feature. Where
      overlap with space-based instruments exists, our results are in excellent
      agreement with previous measurements. A feature at approximately 3.25 microm is
      unexpected and difficult to explain with models that assume local thermodynamic
      equilibrium (LTE) conditions at the 1 bar to 1 x 10(-6) bar pressures typically
      sampled by infrared measurements. The most likely explanation for this feature is
      that it arises from non-LTE emission from CH(4), similar to what is seen in the
      atmospheres of planets in our own Solar System. These results suggest that non
      LTE effects may need to be considered when interpreting measurements of strongly
      irradiated exoplanets.

PMID- 20130646
TI  - Directional water collection on wetted spider silk.
AB  - Many biological surfaces in both the plant and animal kingdom possess unusual
      structural features at the micro- and nanometre-scale that control their
      interaction with water and hence wettability. An intriguing example is provided
      by desert beetles, which use micrometre-sized patterns of hydrophobic and
      hydrophilic regions on their backs to capture water from humid air. As anyone who
      has admired spider webs adorned with dew drops will appreciate, spider silk is
      also capable of efficiently collecting water from air. Here we show that the
      water-collecting ability of the capture silk of the cribellate spider Uloborus
      walckenaerius is the result of a unique fibre structure that forms after wetting,
      with the 'wet-rebuilt' fibres characterized by periodic spindle-knots made of
      random nanofibrils and separated by joints made of aligned nanofibrils. These
      structural features result in a surface energy gradient between the spindle-knots
      and the joints and also in a difference in Laplace pressure, with both factors
      acting together to achieve continuous condensation and directional collection of
      water drops around spindle-knots. Submillimetre-sized liquid drops have been
      driven by surface energy gradients or a difference in Laplace pressure, but until
      now neither force on its own has been used to overcome the larger hysteresis
      effects that make the movement of micrometre-sized drops more difficult. By
      tapping into both driving forces, spider silk achieves this task. Inspired by
      this finding, we designed artificial fibres that mimic the structural features of
      silk and exhibit its directional water-collecting ability.

PMID- 20130647
TI  - Coherently wired light-harvesting in photosynthetic marine algae at ambient
      temperature.
AB  - Photosynthesis makes use of sunlight to convert carbon dioxide into useful
      biomass and is vital for life on Earth. Crucial components for the photosynthetic
      process are antenna proteins, which absorb light and transmit the resultant
      excitation energy between molecules to a reaction centre. The efficiency of these
      electronic energy transfers has inspired much work on antenna proteins isolated
      from photosynthetic organisms to uncover the basic mechanisms at play.
      Intriguingly, recent work has documented that light-absorbing molecules in some
      photosynthetic proteins capture and transfer energy according to quantum
      mechanical probability laws instead of classical laws at temperatures up to 180
      K. This contrasts with the long-held view that long-range quantum coherence
      between molecules cannot be sustained in complex biological systems, even at low
      temperatures. Here we present two-dimensional photon echo spectroscopy
      measurements on two evolutionarily related light-harvesting proteins isolated
      from marine cryptophyte algae, which reveal exceptionally long-lasting excitation
      oscillations with distinct correlations and anti-correlations even at ambient
      temperature. These observations provide compelling evidence for quantum-coherent
      sharing of electronic excitation across the 5-nm-wide proteins under biologically
      relevant conditions, suggesting that distant molecules within the photosynthetic
      proteins are 'wired' together by quantum coherence for more efficient light
      harvesting in cryptophyte marine algae.

PMID- 20130648
TI  - Migrating tremors illuminate complex deformation beneath the seismogenic San
      Andreas fault.
AB  - The San Andreas fault is one of the most extensively studied faults in the world,
      yet its physical character and deformation mode beneath the relatively shallow
      earthquake-generating portion remain largely unconstrained. Tectonic 'non
      volcanic' tremor, a recently discovered seismic signal probably generated by
      shear slip on the deep extension of some major faults, can provide new insight
      into the deep fate of such faults, including that of the San Andreas fault near
      Parkfield, California. Here I examine continuous seismic data from mid-2001 to
      2008, identifying tremor and decomposing the signal into different families of
      activity based on the shape and timing of the waveforms at multiple stations.
      This approach allows differentiation between activities from nearby patches of
      the deep fault and begins to unveil rich and complex patterns of tremor
      occurrence. I find that tremor exhibits nearly continuous migration, with the
      most extensive episodes propagating more than 20 kilometres along fault strike at
      rates of 15-80 kilometres per hour. This suggests that the San Andreas fault
      remains a localized through-going structure, at least to the base of the crust,
      in this area. Tremor rates and recurrence behaviour changed markedly in the wake
      of the 2004 magnitude-6.0 Parkfield earthquake, but these changes were far from
      uniform within the tremor zone, probably reflecting heterogeneous fault
      properties and static and dynamic stresses decaying away from the rupture. The
      systematic recurrence of tremor demonstrated here suggests the potential to
      monitor detailed time-varying deformation on this portion of the deep San Andreas
      fault, deformation which unsteadily loads the shallower zone that last ruptured
      in the 1857 magnitude-7.9 Fort Tejon earthquake.

PMID- 20130649
TI  - A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.
AB  - Obesity has become a major worldwide challenge to public health, owing to an
      interaction between the Western 'obesogenic' environment and a strong genetic
      contribution. Recent extensive genome-wide association studies (GWASs) have
      identified numerous single nucleotide polymorphisms associated with obesity, but
      these loci together account for only a small fraction of the known heritable
      component. Thus, the 'common disease, common variant' hypothesis is increasingly
      coming under challenge. Here we report a highly penetrant form of obesity,
      initially observed in 31 subjects who were heterozygous for deletions of at least
      593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits.
      Nineteen similar deletions were identified from GWAS data in 16,053 individuals
      from eight European cohorts. These deletions were absent from healthy non-obese
      controls and accounted for 0.7% of our morbid obesity cases (body mass index
      (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8),
      odds ratio 43.0), demonstrating the potential importance in common disease of
      rare variants with strong effects. This highlights a promising strategy for
      identifying missing heritability in obesity and other complex traits: cohorts
      with extreme phenotypes are likely to be enriched for rare variants, thereby
      improving power for their discovery. Subsequent analysis of the loci so
      identified may well reveal additional rare variants that further contribute to
      the missing heritability, as recently reported for SIM1 (ref. 3). The most
      productive approach may therefore be to combine the 'power of the extreme' in
      small, well-phenotyped cohorts, with targeted follow-up in case-control and
      population cohorts.

PMID- 20130650
TI  - TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid
      leukaemia.
AB  - Chronic myeloid leukaemia (CML) is caused by a defined genetic abnormality that
      generates BCR-ABL, a constitutively active tyrosine kinase. It is widely believed
      that BCR-ABL activates Akt signalling that suppresses the forkhead O
      transcription factors (FOXO), supporting the proliferation or inhibiting the
      apoptosis of CML cells. Although the use of the tyrosine kinase inhibitor
      imatinib is a breakthrough for CML therapy, imatinib does not deplete the
      leukaemia-initiating cells (LICs) that drive the recurrence of CML. Here, using a
      syngeneic transplantation system and a CML-like myeloproliferative disease mouse
      model, we show that Foxo3a has an essential role in the maintenance of CML LICs.
      We find that cells with nuclear localization of Foxo3a and decreased Akt
      phosphorylation are enriched in the LIC population. Serial transplantation of
      LICs generated from Foxo3a(+/+) and Foxo3a(-/-) mice shows that the ability of
      LICs to cause disease is significantly decreased by Foxo3a deficiency.
      Furthermore, we find that TGF-beta is a critical regulator of Akt activation in
      LICs and controls Foxo3a localization. A combination of TGF-beta inhibition,
      Foxo3a deficiency and imatinib treatment led to efficient depletion of CML in
      vivo. Furthermore, the treatment of human CML LICs with a TGF-beta inhibitor
      impaired their colony-forming ability in vitro. Our results demonstrate a
      critical role for the TGF-beta-FOXO pathway in the maintenance of LICs, and
      strengthen our understanding of the mechanisms that specifically maintain CML
      LICs in vivo.

PMID- 20130651
TI  - Multiple native states reveal persistent ruggedness of an RNA folding landscape.
AB  - According to the 'thermodynamic hypothesis', the sequence of a biological
      macromolecule defines its folded, active (or 'native') structure as a global
      energy minimum in the folding landscape. However, the enormous complexity of
      folding landscapes of large macromolecules raises the question of whether there
      is in fact a unique global minimum corresponding to a unique native conformation
      or whether there are deep local minima corresponding to alternative active
      conformations. The folding of many proteins is well described by two-state
      models, leading to highly simplified representations of protein folding
      landscapes with a single native conformation. Nevertheless, accumulating
      experimental evidence suggests a more complex topology of folding landscapes with
      multiple active conformations that can take seconds or longer to interconvert.
      Here we demonstrate, using single-molecule experiments, that an RNA enzyme folds
      into multiple distinct native states that interconvert on a timescale much longer
      than that of catalysis. These data demonstrate that severe ruggedness of RNA
      folding landscapes extends into conformational space occupied by native
      conformations.

PMID- 20130652
TI  - Experimental evidence for a frustrated energy landscape in a three-helix-bundle
      protein family.
AB  - Energy landscape theory is a powerful tool for understanding the structure and
      dynamics of complex molecular systems, in particular biological macromolecules.
      The primary sequence of a protein defines its free-energy landscape and thus
      determines the folding pathway and the rate constants of folding and unfolding,
      as well as the protein's native structure. Theory has shown that roughness in the
      energy landscape will lead to slower folding, but derivation of detailed
      experimental descriptions of this landscape is challenging. Simple folding models
      show that folding is significantly influenced by chain entropy; proteins in which
      the contacts are local fold quickly, owing to the low entropy cost of forming
      stabilizing, native contacts during folding. For some protein families, stability
      is also a determinant of folding rate constants. Where these simple metrics fail
      to predict folding behaviour, it is probable that there are features in the
      energy landscape that are unusual. Such general observations cannot explain the
      folding behaviour of the R15, R16 and R17 domains of alpha-spectrin. R15 folds
      approximately 3,000 times faster than its homologues, although they have similar
      structures, stabilities and, as far as can be determined, transition-state
      stabilities. Here we show that landscape roughness (internal friction) is
      responsible for the slower folding and unfolding of R16 and R17. We use chimaeric
      domains to demonstrate that this internal friction is a property of the core, and
      suggest that frustration in the landscape of the slow-folding spectrin domains
      may be due to misdocking of the long helices during folding. Theoretical studies
      have suggested that rugged landscapes will result in slower folding; here we show
      experimentally that such a phenomenon directly influences the folding kinetics of
      a 'normal' protein, that is, one with a significant energy barrier that folds on
      a relatively slow, millisecond-second, timescale.

PMID- 20130653
TI  - Structure of the amantadine binding site of influenza M2 proton channels in lipid
      bilayers.
AB  - The M2 protein of influenza A virus is a membrane-spanning tetrameric proton
      channel targeted by the antiviral drugs amantadine and rimantadine. Resistance to
      these drugs has compromised their effectiveness against many influenza strains,
      including pandemic H1N1. A recent crystal structure of M2(22-46) showed electron
      densities attributed to a single amantadine in the amino-terminal half of the
      pore, indicating a physical occlusion mechanism for inhibition. However, a
      solution NMR structure of M2(18-60) showed four rimantadines bound to the carboxy
      terminal lipid-facing surface of the helices, suggesting an allosteric mechanism.
      Here we show by solid-state NMR spectroscopy that two amantadine-binding sites
      exist in M2 in phospholipid bilayers. The high-affinity site, occupied by a
      single amantadine, is located in the N-terminal channel lumen, surrounded by
      residues mutated in amantadine-resistant viruses. Quantification of the protein
      amantadine distances resulted in a 0.3 A-resolution structure of the high
      affinity binding site. The second, low-affinity, site was observed on the C
      terminal protein surface, but only when the drug reaches high concentrations in
      the bilayer. The orientation and dynamics of the drug are distinct in the two
      sites, as shown by (2)H NMR. These results indicate that amantadine physically
      occludes the M2 channel, thus paving the way for developing new antiviral drugs
      against influenza viruses. The study demonstrates the ability of solid-state NMR
      to elucidate small-molecule interactions with membrane proteins and determine
      high-resolution structures of their complexes.

PMID- 20130655
TI  - Vaccination with a potent DNA vaccine targeting B-cell epitopes of hGRP induces
      prophylactic and therapeutic antitumor activity in vivo.
AB  - Gastrin-releasing peptide (GRP), a bombesin-like peptide, is an autocrine or
      paracrine growth factor that can stimulate the growth of various cancer cells,
      making it an ideal target antigen to develop vaccines against cancer. In this
      study, we developed a novel DNA vaccine that encodes six tandem repeats of B-cell
      epitope GRP(18-27) (GRP6) flanked by HSP65 as carrier and four tandem repeats of
      mycobacterial HSP70(407-426) (M4) as helper T-cell epitopes for enhancement of
      immunogenicity. When intramuscularly immunized to mice, this anti-GRP DNA vaccine
      induced GRP-specific antibody (Ab) responses that were at least 10-fold higher in
      magnitude compared with HSP65-GRP6 protein vaccine. Both prophylactic and
      therapeutic antitumor immunities induced by vaccination significantly suppressed
      the growth of GRP-dependent prostate carcinoma RM-1 in vivo and prolonged the
      survival of tumor-inoculated mice. Out results also showed that the immune sera
      with high titer of GRP-specific Abs effectively inhibited the growth of tumor in
      mice and dose dependently inhibited proliferation of cultured RM-1 cells in
      vitro, suggesting that the GRP neutralizing Ab is responsible for the protective
      and therapeutic antitumor activity of vaccination. These findings may be of great
      importance in the further exploration of the applications of growth factors
      identified in human in cancer therapy.

PMID- 20130656
TI  - Developmental microbial ecology of the crop of the folivorous hoatzin.
AB  - The hoatzin (Opisthocomus hoazin) is a South American strict folivorous bird,
      with a crop microbial ecosystem that ferments dietary plants. Chicks
      progressively become independent from the adult-fed regurgitated crop liquids,
      and we hypothesized that the crop bacterial ecosystem develops through ecological
      succession mechanisms, as they grow into adults. The aim of this work was to
      compare the crop bacterial community in hoatzins from three age groups: newly
      hatched chicks, juveniles and adults by sequencing 16S rRNA genes and using the
      G2 PhyloChip. Cloning yielded a total of 2123 nearly full-length sequences binned
      into 294 operational taxonomic units (OTUs) (with <97% homology) belonging to 7
      phyla, with 91% of novel OTUs. The microarray identified a diverse bacterial
      community dominated by Firmicutes and Bacteroidetes, with approximately 1400 taxa
      grouped in 40 phyla that included those detected by cloning. In comparison with
      the adult, the hoatzin chick crop had a greater abundance of Flavobacteriaceae,
      Clostridiaceae and Lachnospiraceae but lacked phyla DSS1, Deferribacteres and
      Termite group 1, which were mostly present in adults. The overall community
      structure of the crop of the hoatzin changes with age in a complex manner,
      probably responding to new niches made available through dietary changes related
      to the transition from dependent to independent feeding.

PMID- 20130657
TI  - Shifts in microbial community structure along an ecological gradient of
      hypersaline soils and sediments.
AB  - Studies of hypersaline ecosystems often yield novel organisms and contribute to
      our understanding of extreme environments. Soils and sediments from La Sal del
      Rey, a previously uncharacterized, hypersaline lake located in southern Texas,
      USA, were surveyed to characterize the structure and diversity of their microbial
      communities. Samples were collected along a transect that spanned vegetated
      uplands, exposed lakebed sediments, and water-logged locations, capturing a wide
      range of environments and physical and chemical gradients. Community quantitative
      PCR (qPCR) was used in combination with tag-encoded pyrosequencing, 16S rRNA gene
      cloning, and Sanger sequencing to characterize the lake's soil and sediment
      microbial communities. Further, we used multivariate statistics to identify the
      relationships shared between sequence diversity and heterogeneity in the soil
      environment. The overall microbial communities were surprisingly diverse,
      harboring a wide variety of taxa, and sharing significant correlations with site
      water content, phosphorus and total organic carbon concentrations, and pH. Some
      individual populations, especially of Archaea, also correlated with sodium
      concentration and electrical conductivity salinity. Across the transect, Bacteria
      were numerically dominant relative to Archaea, and among them, three phyla--the
      Proteobacteria, Bacteroidetes, and Firmicutes--accounted for the majority of taxa
      detected. Although these taxa were detected with similar abundances to those
      described in other hypersaline ecosystems, the greater depth of sequencing
      achieved here resulted in the detection of taxa not described previously in
      hypersaline sediments. The results of this study provide new information
      regarding a previously uncharacterized ecosystem and show the value of high
      throughput sequencing in the study of complex ecosystems.

PMID- 20130658
TI  - Species sorting affects bacterioplankton community composition as determined by
      16S rDNA and 16S rRNA fingerprints.
AB  - To understand the mechanisms determining community composition, it is essential
      to distinctively unravel the importance of local from that of regional processes.
      In this effort, the mechanisms underlying bacterioplankton community assembly
      were analysed in eight lakes of short water residence time (WRT) during a four
      season sampling campaign. Bacterioplankton community composition (BCC) was
      determined using terminal-restriction fragment length polymorphism (t-RFLP) on
      the 16S rRNA gene (16S rDNA) and 16S rRNA. The relationship between similarity in
      BCC between a lake and its major inlet on the one hand and cell import per cell
      production rate from the inlet to the lake epilimnion on the other was used as a
      measure of the importance of cell dispersal (mass effects) for community
      assembly. Low similarities in BCC between lakes and their inlets were observed
      even at short WRTs, and the degree of similarity correlated better with the
      environmental conditions in lakes and streams than with cell import per cell
      production rates. Thus, mass effects seemed less important for local lake BCC in
      comparison to environmental habitat characteristics (species sorting). Analyses
      of 16S rDNA and 16S rRNA community fingerprints yielded similar results,
      indicating that species-sorting dynamics exerted an equally important effect on
      both the abundant and active fraction within the studied bacterioplankton
      communities.

PMID- 20130659
TI  - Reducing dietary sodium intake: the Canadian context.
AB  - Sodium is a required nutrient; Adequate Intakes for adults range from 1200 to
      1500 mg*day(-1), depending on age. The Tolerable Upper Intake Level (UL) for
      sodium is 2300 mg*day(-1) for adults, based on the relationship between sodium
      intake and increased blood pressure. Elevated blood pressure, which is prevalent
      among Canadians, is, in turn, a major risk factor for stroke, cardiovascular
      disease, and renal disease. Sodium intake is not the only determinant of blood
      pressure; other modifiable risk factors include relative mass, physical activity,
      overall dietary quality, and alcohol consumption. However, because >90% of adult
      Canadian men and two thirds of Canadian women have sodium intakes above the UL,
      Health Canada's Working Group on Dietary Sodium Reduction has been charged with
      developing, implementing, and overseeing a strategy to reduce Canadians' sodium
      intakes. It is estimated that approximately 75% of dietary sodium is added during
      food processing; in addition to taste and palatability, sodium also has
      functional roles in food manufacturing and preservation, although the amounts
      used often exceed those required. Because of the central role of processed foods
      in sodium intake, the strategy proposed by Health Canada's Working Group includes
      voluntary reduction of sodium in processed foods and foods sold in food service
      establishments. It will also include an education and awareness campaign, and
      research and surveillance. Initiatives to reduce sodium in other parts of the
      world have demonstrated that it will be challenging to reduce sodium intake to
      the recommended range and will likely require many years to accomplish.

PMID- 20130660
TI  - The fermentable fibre inulin increases postprandial serum short-chain fatty acids
      and reduces free-fatty acids and ghrelin in healthy subjects.
AB  - It is thought that diets high in dietary fibre are associated with reduced risk
      for type 2 diabetes, at least in part because the short-chain fatty acids (SCFAs)
      produced during the colonic fermentation of fibre beneficially influence
      circulating concentrations of free-fatty acids (FFAs) and gut hormones involved
      in the regulation of blood glucose and body mass. However, there is a paucity of
      data showing this sequence of events in humans. Thus, our objective was to
      determine the effect of the fermentable fibre inulin on postprandial glucose,
      insulin, SCFA, FFA, and gut hormone responses in healthy subjects. Overnight
      fasted healthy subjects (n = 12) were studied for 6 h after consuming 400 mL
      drinks, containing 80 g high-fructose corn syrup (80HFCS), 56 g HFCS (56HFCS), or
      56 g HFCS plus 24 g inulin (Inulin), using a randomized, single-blind, crossover
      design. A standard lunch was served 4 h after the test drink. Glucose and insulin
      responses after Inulin did not differ significantly from those after 80HFCS or
      56HFCS. Serum acetate, propionate, and butyrate were significantly higher after
      Inulin than after HFCS drinks from 4-6 h. FFAs fell at a similar rate after all 3
      test drinks, but were lower after Inulin than after 56HFCS at 4 h (0.40 +/- 0.06
      vs. 0.51 +/- 0.06 mmol*L-1; p < 0.05). Compared with 56HFCS, Inulin significantly
      increased plasma glucagon-like peptide-1 concentrations at 30 min, and reduced
      ghrelin at 4.5 h and 6 h. The results are consistent with the hypothesis that
      dietary fibre increases the production of colonic SCFAs, which may reduce type 2
      diabetes risk by reducing postprandial FFAs and favorably affecting gut hormones,
      which regulate food intake.

PMID- 20130661
TI  - The effect of training volume and intensity on competitive cyclists' efficiency.
AB  - The impact of different intensity training on cycling efficiency in competitive
      cyclists is unknown. Twenty-nine endurance-trained competitive male cyclists
      completed 3 laboratory visits during a 12-week training period. At each visit,
      their cycling efficiency and maximal oxygen uptake were determined. After the
      first visit, cyclists were randomly split into 2 groups (A and B). Over the first
      6 weeks, between tests 1 and 2, group A was prescribed specific high-intensity
      training sessions, whereas group B was restricted in the amount of intensive work
      undertaken. After test 2 and for the second 6-week period, group B was allowed to
      conduct high-intensity training. Gross efficiency (GE) increased in group A (+1.6
      +/- 1.4%; p < 0.05) following the high-intensity training, whereas no significant
      change was seen in group B (+0.1 +/- 0.7%; p > 0.05). Group B cyclists increased
      their GE between tests 2 and 3 (+1.4 +/- 0.8%; p < 0.05) but no changes in GE
      were observed in group A over this period (+0.4 +/- 0.4%; p > 0.05). Delta
      efficiency (DE) did not change significantly in either group across the study
      period. This study demonstrates that GE is increased following high-intensity
      training in competitive male cyclists after 12 weeks.

PMID- 20130662
TI  - Fat-free mass and gender influences the rapid-phase excess postexercise oxygen
      consumption.
AB  - The purpose of this study was to determine the influence of gender dimorphism and
      body composition on postexercise oxygen consumption during the rapid recovery
      phase. We compared the rapid-phase excess postexercise oxygen consumption (EPOC)
      in men and women matched for age (32.1 years), physical activity status, and
      maximal oxygen consumption (44.7 mL*kg(-1)*min(-1)), but not for body mass or fat
      free mass (FFM). All subjects exercised for 1 h at 50% of their peak capacity.
      Although there were differences between genders in the magnitude of the absolute
      oxygen consumption and EPOC during the rapid phase of recovery, there were no
      differences found when EPOC was corrected for FFM. We conclude that the gender
      differences in the absolute O(2) consumption and EPOC are related to the size of
      the FFM.

PMID- 20130663
TI  - An investigation into the possible physiological mechanisms associated with
      changes in performance related to acute responses to different preactivity
      stretch modalities.
AB  - The aim of this study was to explore the potential mechanisms underlying
      performance changes linked to different warm-up stretch modalities. Twenty-one
      male collegiate-semiprofessional soccer players (age, 20.8 +/- 2.3 years)
      performed under 3 different warm-up conditions: a no-stretch warm-up (WU), a warm
      up including static passive stretches (SPS), and a warm-up incorporating static
      dynamic stretches (SDS). Countermovement jump, drop jump, peak torque, heart
      rate, core temperature, movement kinematics, and electromyography (EMG) were
      recorded for each intervention. Significant increases (p < 0.001) in performance
      were recorded for the countermovement, drop jump, and peak torque measures when
      the SDS was compared with the WU and SPS trials. When mechanism data were
      analysed, heart rate was significantly higher (p < 0.001) in the SDS condition
      compared with the SPS and WU conditions (a pattern also shown with core
      temperature), whereas the WU condition heart rate was also significantly higher
      than the SPS condition heart rate. When EMG data were examined for the rectus
      femoris muscle, significantly greater (p < 0.01) muscle activity was observed in
      the SDS condition compared with the SPS condition. It seems the most likely
      mechanisms to explain the increase in performance in the SDS condition compared
      with the SPS condition are increased heart rate, greater muscle activity, and
      increased peak torque.

PMID- 20130664
TI  - Comparison of on-ice and off-ice graded exercise testing in collegiate hockey
      players.
AB  - The purpose of this study was to compare lactate thresholds (LT) and maximal
      aerobic capacities (VO(2 max) during sport-specific skating (on ice) and cycle
      ergometry (off ice) in collegiate hockey players. We hypothesized that VO(2 max)
      and LT would be higher on ice. We also sought to determine if on-ice and off-ice
      VO(2 max) values were correlated. Twelve collegiate hockey players performed both
      graded exercise protocols in randomized order to fatigue. Both protocols included
      80 s of work during each stage, followed by 40 s of rest to allow for blood
      lactate sampling. VO(2 max) was significantly higher on ice (46.9 +/- 1.0 mL*kg(
      1)*min(-1)) than off ice (43.6 +/- 0.9 mL*kg(-1)*min(-1); p < 0.05). Maximal
      heart rate (HR(max)) was also higher on ice (192.2 +/- 1.8 beats*min(-1)) than
      off ice (186.0 +/- 1.5 beats*min(-1); p < 0.01). LT was drastically higher on ice
      than off ice as a percentage of VO(2 max) (85.9% +/- 1.9% vs. 69.7% +/- 1.3%; p <
      0.01) and HR(max) (90.1% +/- 1.3% vs. 79.4% +/- 1.6%; p < 0.01). Finally, no
      correlation existed between VO(2 max) values off ice and on ice (r = -0.002; p =
      0.99). Our results indicate that off-ice VO(2 max) and LT are not adequate
      predictors of on-ice VO(2 max) and LT in collegiate hockey players. These
      findings challenge the use of cycle ergometry to assess aerobic capacity at
      events such as the National Hockey League Entry Draft combine. We suggest that
      hockey players be tested in a sport-specific manner, regardless of whether those
      tests are performed on ice or off ice.

PMID- 20130665
TI  - Glycemic and urinary volume responses in diabetic mellitus rats treated with
      Solanum lycocarpum.
AB  - Dietary fiber performs important functions in diabetes mellitus control and
      treatment. In this study, we evaluate the reduction in plasma glucose after the
      treatment of diabetic rats with high-fiber Solanum lycocarpum flour. We found
      that serum glucose, water and food intake, urine excretion, and urine sodium
      concentration were reduced in S. lycocarpum flour-treated diabetic rats (TDRs),
      compared with diabetic control rats (DCRs). In addition, TDRs did not show signs
      of kidney hypertrophy, unlike those in the DCR group. These results suggest that
      the use of S. lycocarpum flour can be an effective support in diabetes mellitus
      treatment.

PMID- 20130666
TI  - Identification and characterization of the critical physically demanding tasks
      encountered by correctional officers.
AB  - The purpose of this investigation was to identify the critical tasks encountered
      by correctional officers (COs) on the job and to conduct a comprehensive
      assessment and characterization of the physical demands of these tasks. These are
      the first steps in developing a fitness screening test for COs in compliance with
      recent legislation. The most important, physically demanding, and frequently
      occurring tasks were identified using Delphi methodology, focus groups, and
      questionnaire responses from 190 experienced front-line COs. These tasks were
      structured into emergency response scenarios for which a physical and
      physiological characterization was conducted to verify their relative physical
      demands analysis. Oxygen consumption and the forces exerted by COs were
      quantified while they were responding and then controlling and restraining
      inmates. The female COs used less force than the male COs did to control and
      restrain the same inmates (body control = 46 vs. 60 kg, wrist hold = 32 vs. 49
      kg, and arm retraction = 37 vs. 47 kg) and did not exert their maximal strength
      during their control and restraint activities. The mean oxygen consumption of the
      female and male COs while performing the on-the-job tasks was similar (39.5 vs.
      38.5 mL.kg-1.min-1). We concluded that the essential components of a fitness
      screening protocol for CO applicants are cell search, expeditious response, body
      control, arm restraint, inmate relocation, and an assessment of aerobic fitness.
      The criterion performance standards for completing these tasks in a circuit were
      set at the job performance level of safe and efficient female COs.

PMID- 20130667
TI  - Construction, validation, and derivation of performance standards for a fitness
      test for correctional officer applicants.
AB  - The purpose of this investigation was to develop and validate a fitness test for
      correctional officer (CO) applicants (FITCO) and to establish associated
      standards of acceptability. The FITCO incorporated the most important, physically
      demanding, and frequently occurring tasks of a CO. It consists of (i) a simulated
      cell search; (ii) an emergency response circuit (ERC), involving a 60-m run while
      scaling 4 sets of stairs, followed by simulations of an inmate control, wrist
      restraint, arm retraction, and 40-m mannequin drag; and (iii) a test of aerobic
      fitness. The validity of the FITCO was established by very high congruence
      between the oxygen consumption, heart rate, and rating of perceived exertion of
      incumbent COs while performing the ERC with the same measurements while COs were
      performing the on-the-job tasks on which the ERC was based. The content validity
      of the FITCO was confirmed by very high Likert ratings (>6 on a 7-point scale) by
      both male and female incumbent COs of all ages concerning the importance,
      relatedness, physical demands, and overall appropriateness of the FITCO for
      evaluating CO applicants. We conclude that because the forces built into the ERC
      and the FITCO standards were both derived from the performance of safe and
      efficient incumbent female COs of all ages, and both the validity and test-retest
      reliability (intraclass correllation coefficient = 0.977) of the FITCO are very
      high, the FITCO was properly constructed to meet the requirements of the Supreme
      Court of Canada's Meiorin Decision.

PMID- 20130668
TI  - Applying the Meiorin Decision requirements to the fitness test for correctional
      officer applicants; examining adverse impact and accommodation.
AB  - The fitness test for correctional officer applicants (FITCO) was constructed a
      priori to conform to requirements established by the Meiorin Decision of the
      Supreme Court of Canada. A critical obligation from this decision is to determine
      whether the FITCO has the potential of adverse impact on any subpopulation of
      applicants and, if so, whether it is possible to provide accommodation. The FITCO
      pass rate was 28.6% for 56 women and 72.7% for 22 men, which indicates adverse
      impact on the female applicants. There was no specific adverse impact on minority
      applicants. To evaluate training as accommodation for adverse impact, a subgroup
      of 40 females and 8 males engaged in a 6-week FITCO-specific training program
      with pre-FITCO and post-FITCO performance evaluations. Over the 6 weeks, the
      overall FITCO pass rate of the females improved to 82.5%, whereas the pass rate
      of the males improved to 100%, indicating that the training program removed the
      adverse impact that the FITCO had on the females. We conclude that although the
      FITCO is likely to have an adverse impact on female correctional officer
      applicants, a 6-week FITCO-specific training program can provide the
      accommodation necessary to overcome the potential adverse impact, and the FITCO
      meets all the requirements established by the Supreme Court of Canada's Meiorin
      Decision.

PMID- 20130671
TI  - What I always wanted to know about instability training.
AB  - A very popular mode of training in recent years has been the use of instability
      devices and exercises to train the core musculature. Instability training is
      viewed by many as the most effective way to train the core; however, evidence on
      this topic paints a slightly different picture. An extensive review of the
      literature by Behm et al. 2010 (Appl. Physiol. Metab. Nutr. 35(1): 91-108)
      identified the fact that instability training can increase core muscle
      activation, but it may not be the best choice in all situations. Unstable
      training can reduce overall muscular power output, which may have important
      implications if the goal of a given training program is to maximize the output or
      physiological stress on a given muscle, as is the case in certain types of
      athletic training or in certain clinical exercise situations. Nevertheless, the
      balance of this evidence leads to the recommendations in the position stand (Behm
      et al. 2010, Appl. Physiol. Metab. Nutr. 35(1): 109-112) that instability
      training can play an important role as part of an overall periodized program for
      an athlete, as part of a rehabilitation program in recovery from injury, or as an
      interesting and novel training mode for the general population in pursuit of
      musculoskeletal health benefits who may not have access to or want to complete
      more intensive free-weight training programs. More research is needed to
      establish the effectiveness of instability training in preventing injury in
      sports, enhancing on-field sport performance, or for use in various clinical
      situations outside of rehabilitation for low back pain.

PMID- 20130672
TI  - The use of instability to train the core musculature.
AB  - Training of the trunk or core muscles for enhanced health, rehabilitation, and
      athletic performance has received renewed emphasis. Instability resistance
      exercises have become a popular means of training the core and improving balance.
      Whether instability resistance training is as, more, or less effective than
      traditional ground-based resistance training is not fully resolved. The purpose
      of this review is to address the effectiveness of instability resistance training
      for athletic, nonathletic, and rehabilitation conditioning. The anatomical core
      is defined as the axial skeleton and all soft tissues with a proximal attachment
      on the axial skeleton. Spinal stability is an interaction of passive and active
      muscle and neural subsystems. Training programs must prepare athletes for a wide
      variety of postures and external forces, and should include exercises with a
      destabilizing component. While unstable devices have been shown to be effective
      in decreasing the incidence of low back pain and increasing the sensory
      efficiency of soft tissues, they are not recommended as the primary exercises for
      hypertrophy, absolute strength, or power, especially in trained athletes. For
      athletes, ground-based free-weight exercises with moderate levels of instability
      should form the foundation of exercises to train the core musculature.
      Instability resistance exercises can play an important role in periodization and
      rehabilitation, and as alternative exercises for the recreationally active
      individual with less interest or access to ground-based free-weight exercises.
      Based on the relatively high proportion of type I fibers, the core musculature
      might respond well to multiple sets with high repetitions (e.g., >15 per set);
      however, a particular sport may necessitate fewer repetitions.

PMID- 20130673
TI  - Canadian Society for Exercise Physiology position stand: The use of instability
      to train the core in athletic and nonathletic conditioning.
AB  - The use of instability devices and exercises to train the core musculature is an
      essential feature of many training centres and programs. It was the intent of
      this position stand to provide recommendations regarding the role of instability
      in resistance training programs designed to train the core musculature. The core
      is defined as the axial skeleton and all soft tissues with a proximal attachment
      originating on the axial skeleton, regardless of whether the soft tissue
      terminates on the axial or appendicular skeleton. Core stability can be achieved
      with a combination of muscle activation and intra-abdominal pressure. Abdominal
      bracing has been shown to be more effective than abdominal hollowing in
      optimizing spinal stability. When similar exercises are performed, core and limb
      muscle activation are reported to be higher under unstable conditions than under
      stable conditions. However, core muscle activation that is similar to or higher
      than that achieved in unstable conditions can also be achieved with ground-based
      free-weight exercises, such as Olympic lifts, squats, and dead lifts. Since the
      addition of unstable bases to resistance exercises can decrease force, power,
      velocity, and range of motion, they are not recommended as the primary training
      mode for athletic conditioning. However, the high muscle activation with the use
      of lower loads associated with instability resistance training suggests they can
      play an important role within a periodized training schedule, in rehabilitation
      programs, and for nonathletic individuals who prefer not to use ground-based free
      weights to achieve musculoskeletal health benefits.

PMID- 20130675
TI  - Communication between the AAA+ ring and microtubule-binding domain of dynein.
AB  - Dyneins are microtubule motors, the core of which consists of a ring of AAA+
      domains. ATP-driven conformational changes of the AAA+ ring are used to drive the
      movement of a mechanical element (termed the linker domain) that provides the
      motor's powerstroke and to change the affinity of the motor for microtubules
      (strong binding during the power stroke and weak binding to allow stepping and
      recocking of the linker domain). Dynein's microtubule-binding domain (MTBD) is
      located at the end of a 10 nm long anti-parallel coiled coil (the stalk) and
      conformational changes that alter the affinity for microtubules must propagate
      through this coiled coil. A recent crystal structure of dynein's MTBD sheds new
      light on how this long-range communication along a coiled coil might occur.

PMID- 20130674
TI  - Applying Hsp104 to protein-misfolding disorders.
AB  - Hsp104, a hexameric AAA+ ATPase found in yeast, transduces energy from cycles of
      ATP binding and hydrolysis to resolve disordered protein aggregates and cross
      beta amyloid conformers. These disaggregation activities are often co-ordinated
      by the Hsp70 chaperone system and confer considerable selective advantages.
      First, renaturation of aggregated conformers by Hsp104 is critical for yeast
      survival after various environmental stresses. Second, amyloid remodeling by
      Hsp104 enables yeast to exploit multifarious prions as a reservoir of beneficial
      and heritable phenotypic variation. Curiously, although highly conserved in
      plants, fungi and bacteria, Hsp104 orthologues are absent from metazoa. Indeed,
      metazoan proteostasis seems devoid of a system that couples protein
      disaggregation to renaturation. Here, we review recent endeavors to enhance
      metazoan proteostasis by applying Hsp104 to the specific protein-misfolding
      events that underpin two deadly neurodegenerative amyloidoses. Hsp104 potently
      inhibits Abeta42 amyloidogenesis, which is connected with Alzheimer's disease,
      but appears unable to disaggregate preformed Abeta42 fibers. By contrast, Hsp104
      inhibits and reverses the formation of alpha-synuclein oligomers and fibers,
      which are connected to Parkinson's disease. Importantly, Hsp104 antagonizes the
      degeneration of dopaminergic neurons induced by alpha-synuclein misfolding in the
      rat substantia nigra. These studies raise hopes for developing Hsp104 as a
      therapeutic agent.

PMID- 20130676
TI  - A role for Cdc48/p97 and Aurora B in controlling chromatin condensation during
      exit from mitosis.
AB  - During cell division, chromosomes condense so that the replicated chromatids can
      be segregated by the mitotic spindle. While condensation is governed by cyclin
      dependent kinase 1 (Cdk1) during mitotic entry and early mitosis, it is still
      poorly understood how condensation is maintained during anaphase after Cdk1
      inactivation, and how decondensation is triggered in telophase. Here, we review
      recent reports that point to a novel role of Aurora B kinase in maintaining
      condensation and preventing premature nuclear envelope formation during exit from
      mitosis. Timely decondensation and nuclear envelope formation at the end of
      mitosis may then be triggered by two mechanisms. One is removing Aurora B
      phosphorylation marks from chromatin by specific phosphatases. The other is
      removing and inactivating Aurora B kinase itself by the ubiquitin system. We have
      recently provided evidence that the AAA ATPase Cdc48/p97 plays a central role in
      the inactivation of Aurora B, as it extracts ubiquitinated Aurora B from
      chromosomes and thus reduces chromatinassociated Aurora B activity.

PMID- 20130677
TI  - Rvb1-Rvb2: essential ATP-dependent helicases for critical complexes.
AB  - Rvb1 and Rvb2 are highly conserved, essential AAA+ helicases found in a wide
      range of eukaryotes. The versatility of these helicases and their central role in
      the biology of the cell is evident from their involvement in a wide array of
      critical cellular complexes. Rvb1 and Rvb2 are components of the chromatin
      remodeling complexes INO80, Swr-C, and BAF. They are also members of the histone
      acetyltransferase Tip60 complex, and the recently identified R2TP complex present
      in Saccharomyces cerevisiae and Homo sapiens; a complex that is involved in small
      nucleolar ribonucleoprotein (snoRNP) assembly. Furthermore, in humans, Rvb1 and
      Rvb2 have been identified in the URI prefoldin-like complex. In Drosophila, the
      Polycomb Repressive complex 1 contains Rvb2, but not Rvb1, and the Brahma complex
      contains Rvb1 and not Rvb2. Both of these complexes are involved in the
      regulation of growth and development genes in Drosophila. Rvbs are therefore
      crucial factors in various cellular processes. Their importance in chromatin
      remodeling, transcription regulation, DNA damage repair, telomerase assembly,
      mitotic spindle formation, and snoRNP biogenesis is discussed in this review.

PMID- 20130678
TI  - Structural and functional implications of phosphorylation and acetylation in the
      regulation of the AAA+ protein p97.
AB  - p97, also known as VCP (valosin-containing protein), is a hexameric AAA+ ATPase
      that participates in a variety of cellular processes. It is believed that p97
      mediates these processes through the binding of various adaptor proteins. Many
      factors govern adaptor binding and the regulatory mechanisms are not yet well
      understood. Sites of phosphorylation and acetylation on p97 have been identified
      and such post-translational modifications may be involved in regulating p97
      function. Phosphorylation and, to a lesser extent, acetylation of p97 have been
      shown to modify its properties - for example, by modulating adaptor binding and
      directing subcellular localization. These modifications have been implicated in a
      number of p97-mediated processes, including misfolded protein degradation,
      membrane fusion, and transcription factor activation. This review describes the
      known phosphorylation and acetylation sites on p97 and discusses their possible
      structural and functional implications.

PMID- 20130679
TI  - DnaA, ORC, and Cdc6: similarity beyond the domains of life and diversity.
AB  - To initiate chromosomal DNA replication, specific proteins bind to the
      replication origin region and form multimeric and dynamic complexes. Bacterial
      DnaA, the eukaryotic origin recognition complex (ORC), and Cdc6 proteins, most of
      which include an AAA+(-like) motif, play crucial roles in replication initiation.
      The importance of ATP binding and hydrolysis in these proteins has recently
      become recognized. ATP binding of Escherichia coli DnaA is required for the
      formation of the activated form of a DnaA multimer on the replication origin. The
      ATP-DnaA multimer can unwind duplex DNA in an origin-dependent manner, which is
      supported by various specific functions of several AAA+ motifs. DnaA-ATP
      hydrolysis is stimulated after initiation, repressing extra initiations, and
      sustaining once-per-cell cycle replication. ATP binding of ORC and Cdc6 in
      Saccharomyces cerevisiae is required for heteromultimeric complex formation and
      specific DNA binding. ATP hydrolysis of these proteins is important for the
      efficient loading of the minichromosome maintenance protein complex, a component
      of the putative replicative helicase. In this review, we discuss the roles of
      DnaA, ORC, and Cdc6 in replication initiation and its regulation. We also
      summarize the functional features of the AAA+ domains of these proteins, and the
      functional divergence of ORC in chromosomal dynamics.

PMID- 20130680
TI  - Towards a unifying mechanism for ClpB/Hsp104-mediated protein disaggregation and
      prion propagation.
AB  - The oligomeric AAA+ chaperones ClpB/Hsp104 mediate the reactivation of aggregated
      proteins, an activity that is crucial for the survival of cells during severe
      stress. Hsp104 is also essential for the propagation of yeast prions by severing
      prion fibres. Protein disaggregation depends on the cooperation of ClpB/Hsp104
      with a cognate Hsp70 chaperone system. While Hsp70 chaperones are also involved
      in prion propagation, their precise role is much less well defined compared with
      its function in aggregate solubilization. Therefore, it remained unclear whether
      both ClpB/Hsp104 activities are based on common or different mechanisms. Novel
      data show that ClpB/Hsp104 uses a motor threading activity to remodel both
      protein aggregates and prion fibrils. Moreover, transfer of both types of
      substrates to the ClpB/Hsp104 processing pore site requires initial substrate
      interaction of Hsp70. Together these data emphasize the similarity of
      thermotolerance and prion propagation pathways and point to a shared mechanistic
      principle of Hsp70-ClpB/Hsp104-mediated solubilization of amorphous and ordered
      aggregates.

PMID- 20130681
TI  - Comparison of the multiple oligomeric structures observed for the Rvb1 and Rvb2
      proteins.
AB  - The Rvb1 and Rvb2 proteins are 2 members of the AAA+ family, involved in roles as
      diverse as chromatin remodeling, transcription, small nucleolar RNA maturation,
      cellular transformation, signaling of apoptosis and mitosis. These proteins are
      capable of playing a role in such diverse cellular activities because they are
      components of different macromolecular assemblies. In the last few years, there
      has been a number of groups reporting on the structure of purified Rvbs. The
      reported results have been rather controversial, because there are significant
      differences observed among the published structures in spite of the high degree
      of homology among these proteins. Surprisingly, contradictions are observed not
      only between structures representing the Rvb proteins from different species, but
      also between protein structures from the same species. This review describes the
      available Rvb structures from different species and also makes a comparative
      analysis of them. Finally, we identify some aspects of these structural studies
      worth pursuing in additional investigations to ensure that the reported
      structures reflect physiologically relevant conformations of the Rvb1-Rvb2
      complex.

PMID- 20130682
TI  - Cryo electron microscopy structures of Hsp100 proteins: crowbars in or out?
AB  - Independent cryo electron microscopy (cryo-EM) studies of the closely related
      protein disaggregases ClpB and Hsp104 have resulted in two different models of
      subunit arrangement in the active hexamer. We compare the EM maps and resulting
      atomic structure fits, discuss their differences, and relate them to published
      experimental information in an attempt to discriminate between models. In
      addition, we present some general assessment criteria for low-resolution cryo-EM
      maps to offer non-structural biologists tools to evaluate these structures.

PMID- 20130683
TI  - Diverse functions of mitochondrial AAA+ proteins: protein activation,
      disaggregation, and degradation.
AB  - In eukaryotes, mitochondria are required for the proper function of the cell and
      as such the maintenance of proteins within this organelle is crucial. One class
      of proteins, collectively known as the AAA+ (ATPases associated with various
      cellular activities) superfamily, make a number of important contributions to
      mitochondrial protein homeostasis. In this organelle, they contribute to the
      maturation and activation of proteins, general protein quality control,
      respiratory chain complex assembly, and mitochondrial DNA maintenance and
      integrity. To achieve such diverse functions this group of ATP-dependent
      unfoldases utilize the energy from ATP hydrolysis to modulate the structure of
      proteins via unique domains and (or) associated functional components. In this
      review, we describe the current status of knowledge regarding the known
      mitochondrial AAA+ proteins and their role in this organelle.

PMID- 20130684
TI  - ATP-bound form of the D1 AAA domain inhibits an essential function of Cdc48p/p97.
AB  - Cdc48p/p97 is a highly conserved essential AAA protein that is required for many
      cellular processes, and is identified as a causative gene for an autosomal
      dominant human disorder, inclusion body myopathy associated with Paget's disease
      of the bone and frontotemporal dementia (IBMPFD). Cdc48p/p97 is composed of an N
      terminal domain, followed by two AAA domains (D1 and D2) whose ATPase activities
      have been characterized extensively. In this study, effects of mutations on the
      essential functions of yeast Cdc48p/p97 in vivo were systematically analyzed.
      IBMPFD-related mutations do not affect the essential functions of Cdc48p/p97.
      Loss of ATPase activity of D2 leads to loss of function of the protein in vivo.
      In contrast, ATPase activity of D1 per se is not essential, but a mutation
      locking D1 in an ATP-bound form is exceptionally lethal. Site-directed and random
      mutagenesis analyses suggest that the ATP-bound form of D1 changes an inter
      domain interaction, thereby perturbing an essential function of Cdc48p/p97.

PMID- 20130686
TI  - Retraction: Hydrogen peroxide affects abscisic acid binding to ABAP1 in barley
      aleurones.

PMID- 20130685
TI  - Utilization of positional isotope exchange experiments to evaluate reversibility
      of ATP hydrolysis catalyzed by Escherichia coli Lon protease.
AB  - Lon protease, also known as protease La, is an ATP-dependent serine protease.
      Despite the presence of a proteolytic Ser-Lys dyad, the enzyme only catalyzes
      protein degradation in the presence of ATP. Lon possesses an intrinsic ATPase
      activity that is stimulated by protein and certain peptide substrates. Through
      sequence alignment and analysis, it is concluded that Lon belongs to the AAA+
      protein family. Previous kinetic characterization of the ATPase domain of
      Escherichia coli Lon protease implicates a half-site reactivity model in which
      only 50% of the ATP bound to Lon are hydrolyzed to yield ADP; the remaining
      ATPase sites remain bound with ATP and are considered non-catalytic. In this
      model, it is implied that ATP hydrolysis is irreversible. To further evaluate the
      proposed half-site reactivity model, the reversibility of the ATPase activity of
      E. coli Lon was evaluated by positional isotope exchange experiments. The ATPase
      reactions were conducted in the 18O-enriched buffer such that the extent of 18O
      incorporation into inorganic phosphate generated from ATP hydrolysis could be
      used to evaluate the extent of reversibility in ATP hydrolysis. Collectively, our
      experimental data reveal that the ATPase reaction catalyzed by E. coli Lon in the
      presence and absence of peptide substrate that stimulated the enzyme's ATPase
      activity is irreversible. Therefore, the half-site ATPase reactivity of E. coli
      Lon is validated, and can be used to account for the kinetic mechanism of the ATP
      dependent peptidase activity of the enzyme.

PMID- 20130687
TI  - Comparison of antifungal efficacies of moxifloxacin, liposomal amphotericin B,
      and combination treatment in experimental Candida albicans endophthalmitis in
      rabbits.
AB  - The goal of this study was to compare in vitro and in vivo efficacy of
      moxifloxacin and liposomal amphotericin B (Amp-B) monotherapies and combination
      treatment against Candida albicans in an exogenous endophthalmitis model in
      rabbit eyes. Microplate dilution tests and checkerboard analysis were performed
      to detect in vitro efficacies. Endophthalmitis was induced by intravitreal
      injection of C. albicans in 40 rabbit eyes with simultaneous intravitreal drug
      injection according to prophylactic treatment groups. Group 1 (control group)
      received 0.1 mL of balanced salt solution, group 2 (moxi group) 100 microg
      moxifloxacin/0.1 mL, group 3 (Amp-B group) 10 microg liposomal Amp-B/0.1 mL, and
      group 4 (combi group) both 100 microg moxifloxacin/0.1 mL [DOSAGE ERROR
      CORRECTED] and 10 microg liposomal Amp-B/0.05 mL intravitreally. Clinical
      examination, quantitative analysis of microorganisms, and histopathologic
      examination were performed as in vivo studies. The minimum inhibitory
      concentration of liposomal Amp-B against C. albicans was found to be 1 microg/mL.
      Moxifloxacin showed no inhibition of in vitro C. albicans growth. The minimum
      inhibitory concentration values of liposomal Amp-B for C. albicans were reduced
      two- to eightfold with increasing concentrations of moxifloxacin in vitro. In
      vivo, there was no C. albicans growth in the combi group (zero of eight eyes),
      whereas three eyes (37.5%) showed growth in the Amp-B group. Vitreous
      inflammation, retinal detachment, focal retinal necrosis, and outer nuclear layer
      loss were found to be lower in the moxi group compared with the control group.
      Ganglion cell and inner nuclear layer loss was observed in all eyes (100%) in
      both the moxi and combi groups, whereas only in 25% (two of eight eyes) in the
      Amp-B group. Moxifloxacin strongly augments the efficacy of liposomal Amp-B
      against C. albicans in vitro, although it has no in vitro antifungal activity
      when used alone. It is interesting that we found a synergistic effect for in
      vitro tests but failed to demonstrate it in vivo. When 100 microg
      moxifloxacin/0.1 mL is given intravitreally, it has some toxic effects that are
      limited to the inner retinal layers.

PMID- 20130688
TI  - Optimization and validation of rep-PCR genotypic libraries for microbial source
      tracking of environmental Escherichia coli isolates.
AB  - Escherichia coli can be used to help identify sources of fecal contamination in
      the environment. Escherichia coli genotypic fecal libraries and pattern-matching
      algorithms were assessed for their effectiveness in correctly identifying
      sources. Fecal samples (n = 172) were collected from various sources from three
      agricultural landscapes in Canada. Escherichia coli isolates were fingerprinted
      using BOX- and enterobacterial repetitive intergenic consensus (ERIC) -
      polymerase chain reaction primers, revealing 769 and 1 057 distinct genotypes,
      respectively, for the 9 047 isolates collected in 2004 in Ontario. The average
      rate of correct classification (ARCC) was comparable for BOX- (48%) and ERIC
      based (62%) libraries and between libraries with clones removed per sample (55%)
      and clones removed per unit (54%). ARCC increased with fewer classification units
      (from 44% to 65%). ARCC for k-nearest neighbour (64%) and maximum similarity
      (60%) algorithms were comparable, but maximum similarity had better sensitivity
      and specificity than k-nearest neighbour. Geographical and temporal shifts in
      community composition resulted in loss of accuracy. Several ERIC genotypes (n =
      112) were common between sources and were removed from the library, improving
      ARCC (77%). The latter library proved to be more accurate, but its accuracy with
      respect to sourcing environmental isolates remains to be tested.

PMID- 20130689
TI  - Molecular epidemiology of Staphylococcus aureus in food samples based on the
      protein A gene polymorphic region DNA sequence.
AB  - Foodborne disease due to Staphylococcus aureus is a common and important disease
      worldwide. Molecular typing of S. aureus strains plays a crucial role in
      epidemiological studies examining the origin and performing surveillance of major
      infections. In this survey, we collected 913 food samples and detected 93 S.
      aureus isolates by using culture and biochemical tests. Subsequently, the X
      region of the protein A gene was amplified by the polymerase chain reaction (PCR)
      and amplicons were digested with HaeII and HindIII. Seven different patterns,
      ranging in length between 1200 and 1600 bp, showed gene polymorphism of the spa
      gene. The most prevalent spa types were D (20%) and C (16%) in dairy products and
      D (6%) and E (3%) in meat products. Consequently, 16 genotypes were obtained by
      HaeII digestion. Typeability of PCR - restriction fragment length polymorphism in
      genotyping of S. aureus strains in our study was perfect. Therefore, this method
      is a reliable, rapid, and powerful system in epidemiological investigations.

PMID- 20130690
TI  - Mechanism of boron tolerance in soil bacteria.
AB  - Boron (B) is toxic to living cells at levels above a certain threshold. We
      isolated several B-tolerant bacterial strains from soil samples and studied them
      for possible mechanisms of B tolerance. 16S rRNA gene sequencing and comparative
      phylogenetic analysis demonstrated that the isolates belong to the following 6
      genera: Arthrobacter, Rhodococcus, Lysinibacillus, Algoriphagus, Gracilibacillus,
      and Bacillus. These isolates exhibited B-tolerance levels of 80, 100, 150, 300,
      450, and 450 mmol/L, respectively, whilst maintaining a significantly lower
      intracellular B concentration than in the medium. Statistical analysis showed a
      negative correlation between the protoplasmic B concentration and the degree of
      tolerance to a high external B concentration. The kinetic assays suggest that the
      high B efflux and (or) exclusion are the tolerance mechanisms against a high
      external B concentration in the isolated bacteria.

PMID- 20130691
TI  - Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract.
AB  - Aeromonas caviae has been associated with human gastrointestinal disease. Strains
      of this species typically lack virulence factors (VFs) such as enterotoxins and
      hemolysins that are produced by other human pathogens of the Aeromonas genus.
      Microarray profiling of murine small intestinal extracts, 24 h after oral
      infection with an A. caviae strain, provides evidence of a Th1 type immune
      response. A large number of gamma-interferon (gamma-IFN) induced genes are up
      regulated as well as several tumor necrosis factor-alpha (TNF-alpha) transcripts.
      Aeromonas caviae has always been considered an opportunistic pathogen because it
      lacks obvious virulence factors. This current effort suggests that an A. caviae
      strain can colonize the murine intestinal tract and cause what has been described
      by others as a dysregulatory cytokine response. This response could explain why a
      number of diarrheal waterborne disease cases have been attributed to A. caviae
      even though it lacks obvious enteropathogenic properties.

PMID- 20130692
TI  - The effects of N:P ratio and nitrogen form on four major freshwater bacterial
      taxa in biofilms.
AB  - Bacteria in freshwater systems play an important role in nutrient cycling through
      both assimilatory and dissimilatory processes. Biotic and abiotic components of
      the environment affect these transformations as does the stoichiometry of the
      nutrients. We examined responses of four major taxa of bacteria in biofilms
      subjected to various N:P molar ratios using either nitrate or ammonium as a
      nitrogen source. Fluorescent in situ hybridization was used to enumerate the
      Domain bacteria as well as the alpha-, beta-, and gamma-proteobacteria, and the
      Cytophaga-Flavobacteria cluster. Generally, bacterial responses to the treatments
      were limited. However, the Cytophaga-Flavobacteria and beta-proteobacteria both
      responded more to the ammonium additions than nitrate, whereas, the alpha
      proteobacteria responded more to nitrate additions. The beta-proteobacteria also
      exhibited peak relative abundance at the highest N:P ratio. Nutrient
      concentrations were significantly different after the incubation period, and
      there were distinct changes in the stoichiometry of the microcosms with ammonium.
      We demonstrated that bacteria may play an important role in nutrient uptake, and
      transformation, and can have a dramatic effect on the nutrient stoichiometry of
      the surrounding water. However, although some taxa exhibited differences in
      response to ammonium and nitrate, the impact of nutrient stoichiometry on the
      abundance of the taxa examined was limited.

PMID- 20130693
TI  - Microbial community of salt crystals processed from Mediterranean seawater based
      on 16S rRNA analysis.
AB  - Phylogenetic analysis of 16S rRNA was used to investigate for the first time the
      structure of the microbial community that inhabits salt crystals retrieved from
      the bottom of a solar saltern, located in the coastal area of the Mediterranean
      Sea (Sfax, Tunisia). This community lives in an extremely salty environment of
      250-310 g/L total dissolved salt. A total of 78 bacterial 16S rRNA clone
      sequences making up to 21 operational taxonomic units (OTUs), determined by the
      DOTUR program to 97% sequence similarity, was analyzed. These OTUs were
      affiliated to Bacteroidetes (71.4% of OTUs), and gamma-Proteobacteria and alpha
      Proteobacteria (equally represented by 14.2% of the OTUs observed). The archaeal
      community composition appeared more diverse with 68 clones, resulting in 44 OTUs,
      all affiliated with the Euryarchaeota phylum. Of the bacterial and archaeal
      clones showing <97% 16S rRNA sequence identity with sequences in public
      databases, 47.6% and 84.1% respectively were novel clones. Both rarefaction
      curves and diversity measurements (Simpson, Shannon-Weaver, Chao) showed a more
      diverse archaeal than bacterial community at the Tunisian solar saltern pond. The
      analysis of an increasing clone's number may reveal additional local diversity.

PMID- 20130694
TI  - Culturable bacterial populations associated with ectomycorrhizae of Norway spruce
      stands with different degrees of decline in the Czech Republic.
AB  - The aim of this study was to determine which species of culturable bacteria are
      associated with ectomycorrhizae (ECM) of Norway spruce (Picea abies (L.) Karst)
      in the Sudety Mountains, exposed for years to atmospheric pollutants, acid rain,
      and climatic stress, and to identify particular species that have adapted to
      those conditions. Biolog identification was performed on bacterial species from
      ECM of adult spruce trees and seedlings of stands with low, intermediate, and
      high forest decline. Bacterial diversity in ECM associated with adult spruce
      trees, seedlings, and seedlings grown on monoliths was calculated; although the
      expected values appeared to vary widely, no significant differences among sites
      were observed. Dendrograms based on the identified bacterial species showed that
      stands with low forest decline clustered separately from the others. Principal
      component analysis of the normalized data for ECM-associated species showed a
      clear separation between stands with high forest decline and stands with low
      forest decline for seedlings and a less evident separation for adult spruce
      trees. In conclusion, shifts in ECM-associated culturable bacterial populations
      seem to be associated with forest decline in Norway spruce stands. Some bacterial
      species were preferentially associated with mycorrhizal roots depending on the
      degree of forest decline; this was more evident in seedlings where the species
      Burkholderia cepacia and Pseudomonas fluorescens were associated with,
      respectively, ECM of the most damaged stands and those with low forest decline.

PMID- 20130695
TI  - Analysis of Salmonella and enterococci isolated from rendered animal products.
AB  - The objectives of this study were to determine the current status of bacterial
      contamination in rendered animal products and to analyze Salmonella and
      enterococci isolates from the samples. One hundred and fifty samples were
      provided by various rendering companies across the United States, including the
      following meal types: feather, meat, meat and bone, meat and bone from poultry,
      poultry, and blood meals. The average pH of the meals ranged from 6.16 to 7.36,
      and the moisture content ranged from 1.9% to 11.5%. The total bacterial counts
      were in the range of 1.7 to 6.68 log10 CFU/g, with the highest in blood meal and
      the lowest in meat meal. Enterococcus species were detected in 81.3% of the
      samples and accounted for up to 54% of the total bacterial counts in some
      samples. Both blood meal and feather meal were more contaminated (P < 0.05) with
      enterococci than other meal types, although all blood meals were from a single
      company. Salmonella was detected in 8.7% of the samples. Escherichia coli was not
      detected in any of the samples, but coliforms were detected in four samples.
      Among enterococci isolates, three were vancomycin resistant. Thirteen serotypes
      of Salmonella displayed 16 pulsed-field gel electrophoresis patterns. Pulsed
      field gel electrophoresis analysis has indicated that Salmonella contamination
      was not persistent in the plant environment over time. The D-values for the
      Salmonella isolates at 55, 60, and 65 degrees C were in the ranges of 9.27-9.99,
      2.07-2.28, and 0.35-0.40 min, respectively. These results suggest that the
      presence of Salmonella in the finished products may be due to postprocessing
      contamination. This study has also revealed that the rendering industry has
      microbiologically improved its products since earlier studies were conducted.

PMID- 20130696
TI  - Transformation of Sinorhizobium meliloti MTCC 100 and Mesorhizobium ciceri TAL
      620 by CaCl2 method.
AB  - The CaCl2 method, commonly used for transformation of Escherichia coli, was
      modified and used to develop a simpler and easier transformation method for
      Rhizobia sp. Two species of Rhizobia, Sinorhizobium meliloti MTCC 100 and
      Mesorhizobium ciceri TAL 620, were transformed with the 13.2 kb binary vector
      pGA482. At an optical density of 0.4, the transformation efficiencies in
      Sinorhizobium meliloti MTCC 100 and Mesorhizobium ciceri TAL 620 were 104 and
      103, respectively. Competent cells of Sinorhizobium meliloti MTCC 100 were
      prepared at different growth intervals and transformed by the same vector. A
      maximum transformation efficiency of 104 was achieved at an optical density of
      0.5.

PMID- 20130697
TI  - Short hairpin RNA-mediated inhibition of measles virus replication in vitro.
AB  - Rab9 has been identified as a key component for the replication of measles virus
      (MV). In this study, gene-specific shRNAs were developed to suppress the
      replication of MV in culture cells by silencing the expression of Rab9 GTPase
      gene. Rab9 GTPase gene-specific shRNAs were designed and cloned into the
      expression vector of pSUPER.neo+EGFP. Vero-E6 cells were transfected with the
      recombinant plasmid via liposome and then infected with MV. The expression of
      Rab9 GTPase mRNA and protein were assayed by RT-PCR and Western blotting,
      respectively. ShRNA-mediated inhibition of MV replication was further evaluated
      by detecting the titer of MV. The results showed that the expression of Rab9
      GTPase was dramatically and stably downregulated by the generated shRNAs
      targeting Rab9 GTPase gene, which contribute to the inhibition of MV replication,
      indicating these shRNAs could be potentially developed into therapeutic agents
      for the treatment of MV infection in the future.

PMID- 20130698
TI  - Effects of the invasive plant garlic mustard (Alliaria petiolata) on bacterial
      communities in a northern hardwood forest soil.
AB  - We compared the effects of the invasive plant Alliaria petiolata (garlic mustard)
      and 2 native plants on soil bacterial communities in a mature mesophytic forest.
      Soil samples were collected from plant patches containing either Alliaria or the
      native plants Allium tricoccum (wild leek) and Gallium triflorum (bedstraw).
      Since Alliaria litter contains secondary compounds that have reported
      antimicrobial properties, soil was collected outside the root zone of the plants
      but within the plant patches such that the soil would have been influenced by the
      litter of the respective plant species but not by plant roots. DNA was extracted
      from the soil samples and used to amplify the 16S rRNA gene region using
      bacterial specific primers. Terminal restriction fragment length polymorphism
      (TRFLP) profiles of each bacterial community were used to examine differences in
      bacterial communities among the plant species and between August and April
      sampling. Bacterial richness, evenness, and diversity were not significantly
      affected by plant species. Non-metric multidimensional scaling (NMS) suggested
      that differences existed between August and April sampling, but that plant
      species litter exerted a much weaker effect on soil bacterial communities. Soil
      physiochemical conditions were significantly correlated with soil bacterial
      communities and may underlie the observed seasonal changes in bacterial
      communities.

PMID- 20130701
TI  - Evisceration, enucleation, and alternatives to globe removal.

PMID- 20130702
TI  - Prevention of steroid-induced osteoporosis is not unique to ophthalmology.

PMID- 20130704
TI  - [Alternatives to mutilating surgery. ].
AB  - OBJECTIVE: The purpose of this study is to suggest an alternative surgery to
      mutilating exenteration and enucleation surgeries in the management of
      nonfunctional, unattractive, and painless eyes. The suggested alternative is
      lamellar keratectomy with conjunctiva recovery. DESIGN: Retrospective study.
      PARTICIPANTS: Four patient cases in a unit with the benefit of this technique.
      METHODS: The surgical processes and results of the four cases were reviewed.
      RESULTS: Postoperative results were most satisfactory with good esthetic results
      and, above all, a better psychological experience of surgery. CONCLUSIONS: For a
      nonfunctional, unattractive, and painless eye, lamellar keratectomy with
      conjunctiva recovery appears to be an appealing alternative to nonconservative
      eyeball surgeries.

PMID- 20130705
TI  - A genetic approach to stratification of risk for age-related macular
      degeneration.
AB  - The genetic determinants of age-related macular degeneration (AMD) are reviewed
      and a novel approach to risk determination based upon inherited genetic
      polymorphisms and smoking history is presented. Although AMD was long thought to
      have primarily an environmental etiology, genetic variation is now known to
      account for the majority of the disease risk, with variations in the genes of the
      complement pathways playing a prominent role. Independent and validated clinical
      studies have implicated the C3 gene and its regulator, complement factor H
      (1q31.1), complement component 2 (6q21.33), and complement factor B (6q21.33).
      Subtle variations in complement activity increase the risk of symptomatic macular
      inflammation with age. A second group of AMD-associated genetic markers may
      aggravate complement-mediated inflammation by permitting retinal oxidative
      damage. Variation within the chromosomal site (10q26) coding a mitochondrial
      associated protein (age-related maculopathy susceptibility 2) and an independent
      variation within the mitochondrial genome itself (A4917G) suggest a contributing
      pathophysiological role of retinal oxidative stress. A genetic panel of disease
      susceptibility markers and smoking history can identify a group of individuals
      with greater than 65% lifetime risk of AMD. The introduction of genetic marker
      testing into clinical practice may identify patients with early disease who may
      be aided by presymptomatic monitoring or inclusion into trials of newer
      prophylactic agents.

PMID- 20130706
TI  - The prevalence of diabetic retinopathy as identified by teleophthalmology in
      rural Alberta.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence of diabetic
      retinopathy (DR) as identified by teleophthalmology in a sample population of
      people with diabetes living in rural Alberta and to identify the risks and
      benefits of a teleophthalmology program for these patients. DESIGN: Retrospective
      consecutive case series. PARTICIPANTS: Three hundred ninety-four diabetic
      patients (788 eyes). METHODS: Medical histories were obtained, following which
      patients underwent visual acuity and intraocular pressure measurements and
      stereoscopic, 7-field, digital retinal photography. Images were graded by
      ophthalmologists in Edmonton, Alta., according to a modified Early Treatment
      Diabetic Retinopathy Study scoring template. Diagnosis, treatment, and follow-up
      recommendations were communicated to local health care providers and data were
      collected for review. RESULTS: Three hundred ninety-four patients (788 eyes) were
      assessed via 593 teleophthalmology visits over the 3-year period. DR was
      identified in 27.2% of patients (2.3% with proliferative DR and 24.9% with
      nonproliferative DR). A variety of other diagnoses, independent of DR, were also
      made. Recommendations for follow-up teleophthalmology and in-person referral were
      completed in 76.8% and 87.3% of patients, respectively, although many were
      completed later than was recommended. Teleophthalmology saved approximately 450
      round trips from Edson to the nearest urban centre (Edmonton) over the 2-year
      period, equating to approximately 1900 hours and 180 000 km of driving.
      CONCLUSIONS: Teleophthalmology can effectively identify DR while reducing travel
      time and distance for patients with diabetes living in a rural community.
      However, many patients did not follow up or attend referral appointments in a
      timely fashion, underscoring the need for ongoing quality assessment.

PMID- 20130707
TI  - Patency of superior ciliary sulcus in aphakic silicone oil-filled eyes: an
      ultrasound biomicroscopy study.
AB  - OBJECTIVE: To assess the patency of the superior ciliary sulcus in aphakic
      silicone oil-filled eyes by ultrasound biomicroscopy (UBM). DESIGN: Prospective
      interventional series. PARTICIPANTS: Twelve eyes of 12 patients were included in
      this study. METHODS: Twelve aphakic silicone oil-filled eyes were evaluated using
      UBM. The UBM examination of the anterior segment was performed using the Humphrey
      Instruments UBM equipped with a high-frequency (50 MHz), high-resolution (50
      microm) transducer. The patients were placed in a semisitting position in which
      their backs were inclined to a suitable angle (about 50 degrees ). They were also
      asked to look straight ahead, to bring the superior ciliary sulcus to the highest
      point of the globe. The probe approached the patients' eyes superiorly at a
      slight angle (about 10 degrees ). Images of the superior ciliary sulcus were
      captured and analyzed. RESULTS: The UBM images demonstrated an intact curved
      aqueous-silicone oil interface that appeared at some distance from and not
      filling the ciliary sulcus. A patent superior ciliary sulcus was thus found in
      all patients, even in those with a widely opened ciliary sulcus. CONCLUSIONS: The
      superior ciliary sulcus maintained its patency in aphakic silicone oil-filled
      eyes. These findings indicate that an iridectomy in a superior position may also
      be effective, although this has not been tested clinically in this report.

PMID- 20130708
TI  - Triple therapy for neovascular age-related macular degeneration (verteporfin
      photodynamic therapy, intravitreal dexamethasone, and intravitreal bevacizumab).
AB  - OBJECTIVE: Age-related macular degeneration is a multifactorial disease involving
      inflammation, neovascularization, and vascular leakage. As a result, a rationale
      exists for investigating combination treatments that target the different
      pathological processes involved in this disease. We propose triple therapy
      consisting of verteporfin photodynamic therapy (PDT), intravitreal bevacizumab,
      and intravitreal dexamethasone. DESIGN: Retrospective chart review. PARTICIPANTS:
      Thirty-two eyes of 30 patients were included. None of the patients demonstrated
      concurrent eye pathology, and none of the patients had received previous
      treatment for their choroidal neovascularization. METHODS: One cycle of triple
      therapy consisted of reduced-fluence PDT (300 mW/cm(2) for 83 seconds to deliver
      25 J/cm(2)) followed immediately by an 800 microg (0.08 mL) intravitreal
      dexamethasone (IVD) injection. At 1 and 7 weeks after PDT and IVD, patients
      received a 1.25 mg (0.05 mL) bevacizumab injection. At 13 weeks after PDT and
      IVD, each patient had a repeat optical coherence tomography and fluorescein
      angiography to assess choroidal neovascularization activity. Patients were
      followed for 12 months. RESULTS: The mean number of treatment cycles was 1.4. The
      mean number of bevacizumab injections was 2.8. Visual acuity improved from 0.74
      (SD 0.33) logMAR (20/100) to 0.53 (SD 0.32) logMAR (20/70) (p < 0.005). Foveal
      thickness decreased from 328 (SD 116) microm to 216 (SD 85) microm (p < 0.001).
      Ninety-four percent of patients lost fewer than 3 lines, 31% gained more than 3
      lines, and 6% lost more than 3 lines. CONCLUSIONS: By combining agents with
      complementary mechanisms of action, triple therapy could maintain visual acuity
      and macular anatomy while allowing a reduction in the number of anti-vascular
      endothelial growth factor injections required.

PMID- 20130709
TI  - The effect of oral acetazolamide on weight gain in children.
AB  - OBJECTIVE: Oral acetazolamide is a potent medical treatment for pediatric
      glaucoma, but ophthalmologists may have concerns that it retards weight gain in
      children and may choose surgical management instead. DESIGN: Retrospective chart
      review. PARTICIPANTS: Twenty-two well children with glaucoma taking acetazolamide
      orally for >or=3 months. METHODS: Abnormal weight gain was determined using
      downward crossing of 2 percentile lines on growth charts and change in z score
      for weight using a hierarchical linear model. RESULTS: One patient with Sturge
      Weber syndrome and growth failure was excluded when growth hormone deficiency was
      diagnosed. Two patients crossed 2 lines downward; both showed metabolic acidosis.
      The trend for the 2 reversed after medication was discontinued. The other 20
      tracked steadily on growth curves. Eleven patients (11/22, 50%) showed a decline
      in z score for weight over the follow-up period, and the remainder showed an
      increase, for an overall estimate of slope in this sample of 0.01, which was not
      significant (p = 0.8). CONCLUSIONS: Oral acetazolamide may cause poor weight gain
      in a small subset of children on treatment. Metabolic acidosis may be a mediating
      factor for growth failure. Our data suggest that acetazolamide does not cause
      significant weight changes in cases of pediatric glaucoma. Growth parameters
      should be followed. Growth hormone deficiency should be considered in Sturge
      Weber syndrome. Prospective study is needed.

PMID- 20130710
TI  - Retinal heparanase expression in streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: Heparanase, an endoglycosidase, exhibits strong proangiogenic capacity
      that can induce vascular endothelial growth factor (VEGF) expression in tumour
      angiogenesis. The purpose of this study was to evaluate heparanase expression and
      its relationship with VEGF in streptozotocin (STZ)-induced diabetic rats'
      retinas. DESIGN: Experimental study. PARTICIPANTS: STZ-induced rats and non
      diabetic control rats. METHODS: Heparanase expression was initially evaluated in
      cultured human retinal microvascular endothelial cells (HRECs) under high-glucose
      conditions by Western blot. Diabetes was induced in Sprague-Dawley rats by STZ
      intraperitoneal injection. Retinal heparanase expression was assayed in rats by
      immunohistochemistry. Heparanase inhibitor (phosphomannopentaose sulfate) was
      administrated to high-glucose-treated HRECs and diabetic rats. VEGF levels were
      evaluated in HRECs and retinas using enzyme-linked immunosorbent assay. RESULTS:
      Heparanase expression was increased in HRECs under high-glucose conditions
      compared with controls (p < 0.01). Immunohistochemical studies indicated that
      heparanase signals were intense in the retinal vascular endothelia of diabetic
      rats, but faint in those of nondiabetic control rats. Quantitative analysis
      showed that heparanase protein expression was increased by 3.2-fold in diabetic
      rats' retinas compared with nondiabetic rats' retinas (p < 0.01). VEGF level was
      increased, as was heparanase expression, in high-glucose-treated HRECs and in the
      retinas of diabetic rats, and these increases were significantly decreased by
      phosphomannopentaose sulfate administration (p < 0.01). CONCLUSIONS: Heparanase
      expression was upregulated and associated with an increase of VEGF expression in
      STZ-induced diabetic rat retinas. The data suggest that heparanase may be
      involved in the development of diabetic retinopathy and represents a possible
      novel target for therapeutic intervention.

PMID- 20130711
TI  - The effect of combined topical-intracameral anaesthesia on neuroleptic
      requirements during cataract surgery.
AB  - OBJECTIVE: To evaluate whether the addition of intracameral lidocaine to topical
      anaesthesia during cataract surgery leads to a decrease in the administration of
      intraoperative midazolam and fentanyl. DESIGN: Retrospective case-control study.
      PARTICIPANTS: The eyes of 124 patients undergoing phacoemulsification were
      included in the study, with 62 in the intracameral group and 62 in the control
      group. METHODS: A single-centre, retrospective chart review of cases between
      April and October 2007 in which patients had undergone small-incision
      phacoemulsification with foldable intraocular lens insertion and received
      preoperatively either topical tetracaine 0.5% with unpreserved intracameral
      lidocaine 1% (intracameral group) or topical tetracaine 0.5% alone (control
      group). Intraoperatively, midazolam and fentanyl were administered as needed
      based on pain and anxiety. RESULTS: A total of 124 eyes (124 patients) were
      included. There was no statistically significant difference between the mean
      intraoperative midazolam doses given for the 2 groups (p = 0.08). The mean
      intraoperative dose of fentanyl was lower in the intracameral than in the control
      group (p < 0.0001). A comparison of intraoperative fentanyl requirements between
      groups using a multivariate regression analysis for age, gender, surgical time,
      and preoperative fentanyl levels confirmed the lower need for intraoperative
      fentanyl in the intracameral compared with the control group (p = 0.0037). There
      were no anaesthetic complications among any of the study patients. CONCLUSIONS:
      Patients receiving topical tetracaine 0.5% with unpreserved intracameral
      lidocaine 1% during cataract surgery demonstrated a reduction in intraoperative
      fentanyl requirements. Surgeons performing cataract surgery under topical
      anaesthesia should consider the addition of intracameral lidocaine 1% to decrease
      fentanyl requirements and improve patient safety and comfort.

PMID- 20130712
TI  - The relationship between scotoma displacement and preferred retinal loci in low
      vision patients with age-related macular degeneration.
AB  - OBJECTIVE: Adaptive strategies in low-vision patients with age-related macular
      degeneration use preferred retinal loci (PRLs) for the purpose of achieving
      better visual function. In the process of redirecting the eye toward the PRL,
      central scotomata are displaced eccentrically. The consequential effect of the
      first on the second may offer an indirect method for PRL identification. The
      purpose of this study was to clarify the relationship between scotoma
      displacement and PRL location. DESIGN: Prospective, nonrandomized, observational
      case series. PARTICIPANTS: Forty-one adults with a confirmed diagnosis of age
      related macular degeneration. METHODS: Scotoma characteristics were obtained with
      automated perimetry. PRL topography was obtained with the Nidek MP-1 instrument.
      Outcome measures selected for this study were scotoma displacement and PRL
      eccentricities estimates. RESULTS: We tested 16 males and 25 females aged 70-98
      years (mean 82.5 [SD 6.71] years) with best-corrected visual acuity of 0.81 (SD
      0.24) logMar units (20/128). PRL location logically matched scotoma displacement
      in 30 study subjects (73.17%, p < 0.00432). In this subgroup (n = 30), PRL
      eccentricity (5.55 [SD 3.35] degrees ) was almost identical to scotoma
      displacement eccentricity (5.22 [SD 1.98] degrees )(p < 0.65). CONCLUSIONS:
      Scotoma displacement recorded with macular perimetry methods offers reasonable
      indirect estimates of PRL location.

PMID- 20130713
TI  - Concept of a functional retinal locus in age-related macular degeneration.
AB  - PURPOSE: Preferred retinal loci used for eccentric fixation in patients with age
      related macular degeneration (AMD) may be different from the eccentric
      neighbouring loci of highest retinal sensitivity. This study was designed to
      highlight the conceptual difference between the 2 and the concept of a functional
      retinal locus encompassing both the preferred retinal locus and the locus with
      highest retinal sensitivity. DESIGN: Prospective, nonrandomized, observational
      case series. PARTICIPANTS: We recruited 15 adults with documented AMD, low
      vision, and best-corrected visual acuity of 20/50-20/400 in the better eye.
      METHODS: Automated microperimetry methods were used to assess topographic retinal
      sensitivity and location of preferred retinal loci. RESULTS: Mean (SD) age for
      the group was 85.1 (6.5) years. Mean (SD) best-corrected visual acuity measured
      was 0.88 (0.25) logMar units (20/150). The mean (SD) eccentricity of the
      preferred retinal locus used for fixation was different from the eccentricity of
      the area with highest retinal sensitivity in the same eye (7.53 degrees [2.47
      degrees ] vs 9.30 degrees [2.93 degrees ], respectively; p < 0.0003). The
      oculomotor efficiency score measured 82%. The mean (SD) retinal sensitivity at
      the preferred retinal loci was inferior to that of loci with highest retinal
      sensitivity (5.83 [4.26] vs 8.60 [3.06] dB, respectively; p < 0.0007). The
      highest correlation was measured between potential visual acuity estimates and
      estimates of retinal sensitivity at the highest retinal sensitivity loci (p <
      0.0048). CONCLUSIONS: Preferred retinal loci and highest retinal sensitivity loci
      are not identical in AMD cases. A new concept of functional retinal locus is
      proposed to define their relation. A new concept of an oculomotor efficiency
      score is proposed to define oculomotor abilities when macular function is lost.

PMID- 20130714
TI  - Changes in corneal thickness, curvature, and anterior chamber depth during the
      menstrual cycle.
AB  - OBJECTIVE: To determine the variations in corneal thickness values, keratometry
      readings, and anterior chamber depths (ACD) during the menstrual cycle of young
      women using the noncontact Scheimpflug imaging technique. DESIGN: Prospective
      cohort study. PARTICIPANTS: Fourteen women with regular menstrual cycles who were
      not taking contraceptive pills were enrolled and had measurements taken every
      other day during a full menstrual cycle, starting from the first day. None used
      contact lenses or regular medication, and none had systemic disease or history of
      eye surgery. METHODS: The thickness at the centre, superior, inferior, temporal,
      nasal, and thinnest point of the cornea, the keratometry readings, and the ACD
      values measured with the Pentacam were recorded. We used data on days 1, 3, and 5
      of the studied cycle, and counting backwards, 2, 4, 6, 12, 14, and 16 days before
      the first day of the next cycle. RESULTS: The mean differences between 2 points
      of time were not statistically significant (p > 0.05) for any variable. The mean
      difference between any 2 paired thickness measurements was less than 5.0 microm.
      CONCLUSIONS: Contrary to our expectations and previous findings using ultrasound
      pachymetry, we found no clinically or statistically significant differences
      between the repeated measurements with the Pentacam. This could indicate that the
      Pentacam is a clinical tool with less variability when performing serial
      measurements and follow-up examinations.

PMID- 20130715
TI  - Intravenous immunoglobulin in recurrent-relapsing inflammatory optic neuropathy.
AB  - OBJECTIVE: Recurrent-relapsing inflammatory optic neuropathy, including chronic
      relapsing inflammatory and autoimmune optic neuropathies, is rare, but can cause
      severe visual loss. Long-term steroids may preserve vision, yet side effects are
      frequent. We describe our experience with intravenous immunoglobulins (IVIg).
      DESIGN: A semi-prospective case series from 4 medical centres. PARTICIPANTS:
      Patients with steroid responsive recurrent-relapsing optic neuropathy. METHODS:
      Semiprospective case series of IVIg treatment in steroid-responsive recurrent
      relapsing optic neuropathy at 4 medical centres. Outcome measures included visual
      outcome; time to, and duration of, remission; duration of corticosteroid use; and
      adverse events. RESULTS: Vision stabilized in all 6 patients treated with IVIg
      without steroids for extended periods of time. None improved and none worsened.
      One adverse event occurred during an IVIg infusion after 3 uneventful years of
      IVIg maintenance. Average steroid use prior to IVIg was 12 months. After IVIg
      treatment, 5/6 patients no longer required corticosteroids. Two patients
      experienced late relapses on IVIg, one of whom was treated with cyclosporine, the
      other with steroids. CONCLUSIONS: IVIg can be considered an effective steroid
      sparing agent in selected cases with steroid-dependent recurrent-relapsing
      autoimmune optic neuropathy.

PMID- 20130716
TI  - Mucinous eccrine adenocarcinoma of the eyelid: report of 6 cases.
AB  - OBJECTIVE: To report on patients with mucinous eccrine adenocarcinoma of the
      eyelid. DESIGN: Retrospective case series. PARTICIPANTS: Biopsy specimens of 6
      patients with eyelid neoplasm were obtained. The pathologic diagnoses were
      mucinous eccrine adenocarcinomas. METHODS: The medical records, including
      demographic, clinical, histopathologic, and follow-up information, were reviewed.
      RESULTS: Five patients underwent surgical removal of the lesion by means of Mohs
      micrographic surgery. Four of these patients were doing well; 1 of them, with
      positive margins of resection, had 2 recurrences. One case was lost to follow-up.
      CONCLUSIONS: Mucinous eccrine adenocarcinoma is an uncommon adnexal tumour that
      can involve the eyelid, has low metastasis and mortality, but can be invasive or
      locally recur. Mohs micrographic surgery is a recommended treatment of mucinous
      eccrine adenocarcinoma of the eyelid.

PMID- 20130718
TI  - Awareness of industry bias (management of dysfunctional tear syndrome: a Canadian
      consensus. Vol. 44[4]).

PMID- 20130719
TI  - Common variable immunodeficiency in pediatric neurosarcoidosis (protean
      manifestations of pediatric neurosarcoidosis. Vol. 44[4]).

PMID- 20130720
TI  - Osteoporosis prophylaxis prescribing patterns in ophthalmology patients treated
      with long-term corticosteroids.

PMID- 20130721
TI  - Considering amyloidosis in patients with clinically unresponsive vitreous
      inflammation (Oculoleptomeningeal amyloidosis in 3 individuals with transthyretin
      variant Tyr69His. Vol. 44[3]).

PMID- 20130722
TI  - Vitritis and retinal vasculitis as presenting signs of monoclonal gammopathy of
      unknown significance with progression to multiple myeloma.

PMID- 20130723
TI  - Regression of soft drusen and drusenoid pigment epithelial detachment following
      intravitreal anti-vascular endothelial growth factor therapy.

PMID- 20130724
TI  - Merkel cell carcinoma of the eyelid: a report of 2 cases.

PMID- 20130725
TI  - Cryptophthalmos associated with orbito-palpebral cysts: a case report.

PMID- 20130726
TI  - Intraocular framycetin sulphate ointment after sutureless clear corneal section
      phacoemulsification.

PMID- 20130727
TI  - Giant spontaneously regressed retinoblastoma.

PMID- 20130728
TI  - Histoplasma capsulatum endophthalmitis in southeastern Ontario.

PMID- 20130729
TI  - Macular thickening in acute anterior uveitis with a 6-month remission period.

PMID- 20130732
TI  - Role of the RhoA/Rho-kinase pathway in the regulation of pulmonary
      vasoconstrictor function.
AB  - Calcium is the major intracellular messenger that triggers smooth muscle
      contraction. The study of calcium-binding proteins, such as calmodulin and its
      downstream effectors, reveals critical regulation of smooth muscle contraction by
      protein kinases and phosphatases. Moreover, the small GTP-binding protein RhoA
      and its downstream effector protein, Rho-kinase, have been shown to play a novel
      role in the regulation of smooth muscle contraction. Studies have shown that the
      activation of Rho-kinase is involved in the development of endothelial
      dysfunction, inflammation, restenosis, and increased vascular tone in a number of
      cardiovascular disorders. Because inhibitors of this pathway promote vasodilation
      independent of the mechanism that increases vasoconstrictor tone, it is our
      hypothesis that Rho-kinase is constitutively active in regulating vasoconstrictor
      tone in the pulmonary and systemic vascular beds. Studies in the literature
      suggest that the RhoA/Rho-kinase pathway has an important role in the
      pathogenesis of pulmonary hypertension.

PMID- 20130733
TI  - Acute hypertensive pulmonary edema: a new paradigm.
AB  - Although acute hypertensive pulmonary edema is sometimes regarded as the most
      severe form of heart failure, at the peak of symptoms, hearts perform well above
      resting levels and cannot be said to be failing. Another characteristic of the
      condition, the rapidity of its onset and reversal when properly treated, suggests
      positive feedback as a causal mechanism. It is proposed that the syndrome results
      from a feedback loop with increased sympathetic tone as the efferent output,
      increased pulmonary vascular pressure as the stimulus to increased sympathetic
      tone, and positive feedback occurring because elevated sympathetic tone
      constricts systemic veins, thereby transferring blood from peripheral veins to
      the pulmonary vasculature. Evidence for the proposed mechanism derives from all
      the empirical treatments that have evolved. All remove blood from the pulmonary
      circuit, and all but the oldest, bloodletting, do so by transferring blood from
      the pulmonary circuit to the peripheral veins.

PMID- 20130734
TI  - High-frequency oscillation and surfactant treatment in an acid aspiration model.
AB  - Both exogenous surfactant therapy and high-frequency oscillation (HFO) have been
      proposed as clinical interventions in acute respiratory distress syndrome (ARDS).
      The combination of these 2 interventions has not been studied in a relevant model
      of ARDS. It was hypothesized that surfactant treatment combined with HFO is
      superior to either surfactant treatment or HFO alone in a model of ARDS. Adult
      rats had lung injury induced by instillation of 0.1 mol/L HCl, followed by
      randomization to one of 4 groups: Conventional mechanical ventilation (CMV) + air
      (no treatment), CMV + surfactant, HFO + air, and HFO + surfactant. Oxygenation,
      lung compliance, surfactant, and cytokine concentrations in the lung lavage were
      analyzed. The results showed superior oxygenation in HFO ventilated animals
      regardless of surfactant treatment compared with CMV. Nonsurfactant-treated
      animals ventilated with HFO had a significantly greater proportion of large
      aggregates, and had greater lung compliance compared with non-surfactant-treated
      animals ventilated with CMV. Surfactant therapy combined with HFO provided no
      advantages with respect to these outcomes. These data suggest an advantage of HFO
      over CMV when exogenous surfactant was not given, and that surfactant treatment
      combined with HFO was not superior to HFO ventilation alone.

PMID- 20130735
TI  - Effects of Agaricus brasiliensis mushroom in Walker-256 tumor-bearing rats.
AB  - Agaricus brasiliensis is a mushroom native to Sao Paulo State, Brazil, that is
      studied for its medicinal proprieties. This work aimed to investigate the
      antitumoral activity of A. brasiliensis extracts and pure powdered basidiocarp
      preparation using Walker-256 (W256) tumor-bearing rats, a model for cancer
      related cachexia studies. The rats were treated for 14 days by gavage (136 mg/kg)
      and at the end of the experiment tumors were collected to calculate mass and
      volume. Blood was collected for determination of plasma glucose, albumin, alanine
      aminotransferase (ALT), and aspartate aminotransferase (AST). Hepatic and tumor
      enzymes indicating oxidative stress were also evaluated. The results showed that
      all 4 treatments (pure powdered basidiocarp and aqueous, acid, and alkaline
      extracts) significantly reduced tumor size and promoted gain in body weight.
      Plasmatic analysis showed a reduction in AST level and increased glycemia in the
      treated rats. Pure basidiocarp preparations improved the liver catalase and
      superoxide dismutase activity, but did not change the glutathione S-transferase
      activity. The data collected from the W256 tumor-bearing rats revealed the
      beneficial effects of A. brasiliensis in tumor treatment, mainly related to
      cachexia. The benefits can be partly related to antioxidant activity and to
      reduction of weight loss and tumor growth.

PMID- 20130736
TI  - Renoprotective and blood pressure-lowering effect of dietary soy protein via
      protein kinase C beta II inhibition in a rat model of metabolic syndrome.
AB  - We studied whether substitution of soy protein for casein can improve insulin
      sensitivity, lower blood pressure (BP), and inhibit protein kinase C betaII
      (PKCbetaII) activation in kidney in an acquired model of metabolic syndrome.
      Adult male rats were fed 4 different diets: (i) starch (60%) and casein (20%)
      (CCD), (ii) fructose (60%) and casein (20%) (FCD), (iii) fructose (60%) and soy
      protein (20%) (FSD), and (iv) starch (60%) and soy protein (20%) (CSD). Renal
      function parameters, BP, pressor mechanisms, PKCbetaII expression, oxidative
      stress, and renal histology were evaluated after 60 days. FCD rats displayed
      insulin resistance and significant changes in body weight, kidney weight, urine
      volume, plasma and urine electrolytes accompanied by significant changes in renal
      function parameters compared with CCD rats. Elevated BP, plasma angiotensin
      converting enzyme (ACE) activity, renal oxidative stress, and reduced nitrite
      (NO) and kallikrein activity were observed. Western blot analysis revealed
      enhanced renal expression of membrane-associated PKCbetaII in the FCD group.
      Histology showed fatty infiltration and thickening of glomeruli while urinary
      protein profile revealed a 5-fold increase in albumin. Substitution of soy
      protein for casein improved insulin sensitivity, lowered BP and PKCbetaII
      activation and restored renal function. Antioxidant action, inhibitory effect on
      ACE and PKCbetaII activation, and increased availability of kinins and NO could
      be contributing mechanisms for the benefits of dietary soy protein.

PMID- 20130737
TI  - Antidigoxin antiserum prevents endogenous digitalis-like compound-mediated
      reperfusion injury via modulating sodium pump isoform gene expression.
AB  - Endogenous digitalis-like compound (EDLC) is an endogenous ligand of the
      digitalis receptor and can remarkably inhibit Na+/K+-ATPase activity. Antidigoxin
      antiserum (ADA), a selective EDLC antagonist, may lessen myocardial reperfusion
      injury; however, the molecular mechanisms underlying the effect remain unclear.
      Therefore, this study investigated whether ADA may prevent myocardial reperfusion
      injury and modulate gene expression of sodium pump alpha isoforms. Cardiac
      function was examined in isolated rat hearts subjected to ischemia and
      reperfusion (I/R). The infarct size, EDLC level, Na+/K+-ATPase activity, and the
      levels of mRNA for sodium pump alpha isoforms were measured in vivo I/R rat
      hearts in the presence or absence of ADA. It was found that ADA significantly
      improved the recovery of cardiac function, decreased infarct size, decreased EDLC
      level, and recovered Na+/K+-ATPase activity in I/R hearts. Further studies showed
      that sodium pump alpha1, alpha2, and alpha3 isoform mRNA levels were
      significantly reduced in I/R hearts, and pretreatment with ADA induced a large
      increase in the mRNA levels. These results indicate that EDLC may participate in
      depressing Na+/K+-ATPase activity and sodium pump alpha isoform gene expression
      in I/R heart. It is suggested that treatment with ADA may prevent EDLC-mediated
      reperfusion injury via modulating sodium pump isoform gene expression.

PMID- 20130738
TI  - Leflunomide induces immunosuppression in collagen-induced arthritis rats by
      upregulating CD4+CD25+ regulatory T cells.
AB  - This study was to investigate the effect of leflunomide on the immunosuppressive
      CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) in collagen-induced arthritis
      (CIA) rats. CIA was induced by collagen type II in Wistar rats.
      Immunofluorescence flow cytometry and RT-PCR were used to determine the
      proportion of CD4+CD25+ Tregs and the expression of Foxp3 mRNA, respectively.
      Proliferation of T lymphocytes was assayed with MTT reagent, and the level of
      transforming growth factor beta1 (TGF-beta1) in the supernatant of concanavalin A
      (Con A)-induced T lymphocytes was determined by ELISA kit. Our investigations
      demonstrated that inhibition of arthritis by leflunomide was related to changes
      in CD4+CD25+ Tregs. In addition, A771726, which is the active metabolite of
      leflunomide, promoted the differentiation of spleen lymphocytes into CD4+CD25+
      Tregs, increased antiinflammatory cytokine TGF-beta1 secretion, and adjusted the
      activity of Con A-induced lymphocytes in vitro.

PMID- 20130739
TI  - Role of glucagon-like peptide-1 analogues on insulin receptor regulation in
      diabetic rat hearts.
AB  - This study focused on the regulation and affinity modulation of the insulin
      receptor of coronary endothelium and cardiomyocytes in nondiabetic and STZ
      induced type 1 diabetic rats. Male rats were divided into the following 9 groups:
      nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated
      with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic
      treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co
      treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor
      (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). After
      the rats were treated for 1 month, a first-order Bessel function was employed to
      estimate the insulin binding affinity (with time constant tau = 1/k-n) to its
      receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated
      and CHAPS-treated heart perfusion, respectively. The results showed that diabetes
      (D) decreased the tau value on the coronary endothelium and increased it on
      cardiomyocytes compared with the nondiabetic group (N). Treatment with insulin
      and (or) exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, increased tau on
      the coronary endothelium only. On the coronary endothelium, tau values of DI and
      DIDp were normalized. Western blots of the insulin receptor showed upregulation
      in D, downregulation in DI, and normalization in DE and DDp. Immunohistochemistry
      and RT-PCR findings indicated atrial natriuretic factor (ANF) in all diabetic
      ventricles, thus ascertaining hypertrophy. Therefore, negative myocardial effects
      related to the insulin receptor were diminished in diabetic rats treated with DPP
      IV inhibitor and, more efficiently, by exendin-4.

PMID- 20130740
TI  - Antidiabetic properties of purified polysaccharide from Hedysarum polybotrys.
AB  - Hedysarum polybotrys polysaccharide (HPS) is the principal active fraction
      responsible for the antidiabetic properties of this species. The aim of this
      study was to determine the antidiabetic properties of 4 purified fractions of
      different molecular weight range HPSs (HPS1, HPS2, HPS3, HPS4). HPS3 was selected
      for examination of its hypoglycemic mechanism because of its significant
      hypoglycemic effect in alloxan-induced diabetic mice. The changes in blood
      glucose levels and oral glucose tolerance tests (OGTT) showed that hypoglycemia
      was more pronounced in HPS3-treated groups than in the diabetes mellitus model
      (DM) control group. The interleukin-6, tumor necrosis factor-alpha, leptin, and
      free fatty acid levels were significantly lower in the HPS3-treated groups and
      HPS3 + metformin (HPS3+MET) group than in the DM control group, while plasma
      insulin, hepatic glycogen, superoxide dismutase, and nitric oxide synthetase
      activity were significantly higher. Treatment with HPS3 or HPS3+MET also
      significantly lowered malonaldehyde levels compared with the DM control group,
      while it elevated the nitric oxide and total antioxidant capacity. HPS3 altered
      the plasma lipid levels by lowering cholesterol and triglyceride concentrations,
      while elevating the plasma high-density lipoprotein cholesterol level. Therefore,
      these results suggest that HPS3 may partly ameliorate hyperglycemia and
      hyperlipidemia associated with type 2 diabetes through increased insulin
      secretion, inhibition of lipid peroxidation, promotion of sensitivity to insulin,
      suppression of gluconeogenesis and reduction in the biosynthesis fatty acid,
      cholesterol and cell cytokines related to insulin resistance, and it could be a
      useful adjunct therapy to a proven first-line therapy for type 2 diabetes using
      metformin.

PMID- 20130741
TI  - Caveolin-1 exists and may function in cardiomyocytes.
AB  - Whether ventricular cardiac myocytes of mouse contain caveolin-1 is disputed. It
      has been claimed to be exclusively in nearby endothelial cell profiles. Recently,
      matrix metalloproteinase-2 (MMP-2) was reported to be present in mouse
      ventricular cardiac myocytes, colocalized with caveolin-1, and caveolin-1
      knockout was found to cause the loss of MMP-2 from mouse ventricular cardiac
      myocytes and affect their functioning. To resolve this dispute, we labeled
      cardiac myocytes with caveolin-1 and endothelial cells with caveolin-2. Caveolin
      2 is agreed to be present exclusively in endothelial cells. The results showed
      that mouse ventricular myocytes were labeled with caveolin-1 antibodies
      independently of any caveolin-2 labeling, and endothelial cells were labeled with
      both caveolin-1 and caveolin-2 antibodies. This confirms that caveolin-1 is
      present in mouse ventricular cardiac myocytes as well as endothelial cells.
      Previous evidence confirms that loss of caveolin-1 affects the function of mouse
      ventricular cardiac myocytes and suggests that MMP-2 may be involved.

PMID- 20130742
TI  - Antimuscarinic action of doxorubicin does not involve free-radical formation in
      isolated guinea pig hearts.
AB  - It has been proposed that the cardiotoxicity of anthracycline anticancer drugs
      involves free-radical formation. One early manifestation of toxicity appears to
      be caused by the antimuscarinic actions of these drugs. Accordingly, we examined
      whether the antimuscarinic action of one of these drugs, doxorubicin, is altered
      by antioxidants. In electrically stimulated left atrial muscle preparations
      obtained from guinea pig hearts, doxorubicin significantly increased the tissue
      concentration of thiobarbituric acid-reactive substance indicating increased
      lipid peroxidation. This effect of doxorubicin was significantly suppressed by
      the antioxidants alpha-tocopherol, dexrazoxane, and epigallocatechin gallate.
      Carbachol produced a concentration-dependent negative inotropic effect in our
      atrial preparations. Doxorubicin caused a seemingly parallel rightward shift of
      the concentration-response curve for carbachol. Neither alpha-tocopherol,
      dexrazoxane, nor epigallocatechin gallate reversed this effect of doxorubicin.
      The results indicate that in extirpated heart tissue, doxorubicin causes lipid
      peroxidation through the formation of free radicals. However, this effect of
      doxorubicin is unrelated to its antimuscarinic action.

PMID- 20130744
TI  - An SSR-based genetic linkage map of the model grass Brachypodium distachyon.
AB  - The grass species Brachypodium distachyon (hereafter, Brachypodium) has been
      adopted as a model system for grasses. Here, we describe the development of a
      genetic linkage map of Brachypodium. The genetic linkage map was developed with
      an F2 population from a cross between the diploid Brachypodium lines Bd3-1 and
      Bd21. The map was populated with polymorphic simple sequence repeat (SSR) markers
      from Brachypodium expressed sequence tag (EST) and bacterial artificial
      chromosome (BAC) end sequences and conserved orthologous sequence (COS) markers
      from other grass species. The map is 1386 cM in length and consists of 139 marker
      loci distributed across 20 linkage groups. Five of the linkage groups exceed 100
      cM in length, with the largest being 231 cM long. Assessment of colinearity
      between the Brachypodium linkage map and the rice genome sequence revealed
      significant regions of macrosynteny between the two genomes, as well as
      rearrangements similar to those reported in other grass comparative structural
      genomics studies. The Brachypodium genetic linkage map described here will serve
      as a new tool to pursue a range of molecular genetic analyses and other
      applications in this new model plant system.

PMID- 20130745
TI  - Intra- and intergenomic chromosome pairings revealed by dual-color GISH in
      trigenomic hybrids of Brassica juncea and B. carinata with B. maurorum.
AB  - From dual-color genomic in situ hybridization (GISH) analysis of three trigenomic
      hybrids, Brassica maurorum (MM, 2n = 16) x B. juncea (AABB, 2n = 36) (M.AB), B.
      maurorum x B. carinata (BBCC, 2n = 34) (M.BC), and B. carinata x B. maurorum
      (BC.M), the three genomes of each hybrid were distinguished and autosyndesis and
      allosyndesis were evaluated. In M.AB, up to two autosyndetic bivalents occurred
      among the chromosomes of each genome; a maximum of three allosyndetic bivalents
      appeared between A-B, A-M, and B-M genomes. The similar pairings in M.BC and BC.M
      suggested that the cytoplasm of B. maurorum or B. carinata had no obvious effect
      on chromosome pairing. In M.BC and BC.M, a maximum of one autosyndetic bivalent
      was found for B and M genomes, but two were found for the C genome; from 0 to 2
      allosyndetic bivalents were observed between B-C, B-M, and C-M genomes. The B-M
      allosyndesis frequency was higher than the A-M or C-M allosyndesis frequency in
      these hybrids, revealing the closer relationship of B and M genomes. The
      allosyndesis frequency was higher than the autosyndesis frequency among A, B, and
      C genomes in these combinations, suggesting that intergenomic homoeology was
      higher than intragenomic homoeology. The implications for genome evolution and
      crop breeding are discussed.

PMID- 20130746
TI  - Analysis of ITS1 and ITS2 sequences in Ensis razor shells: suitability as
      molecular markers at the population and species levels, and evolution of these
      ribosomal DNA spacers.
AB  - Internal transcribed spacer 1 and 2 (ITS1 and ITS2) sequences were analysed in
      Ensis razor shells (Mollusca: Bivalvia: Pharidae). We aimed to (1) test ITS1 and
      ITS2 as molecular markers at the population level in the successful alien E.
      directus (Conrad, 1843); (2) test these spacers at the species level in E.
      directus and three other Ensis species, E. siliqua (L., 1758), E. macha (Molina,
      1782), and E. magnus (Schumacher, 1817); and (3) analyse the evolutionary
      processes that may be shaping Ensis ITS1 and ITS2 extant variation. In E.
      directus, despite the intragenomic divergence detected, ITS1 and ITS2 were
      informative in differentiating the geographic areas considered (Denmark and
      Canada) by means of both the insertion-deletion polymorphism and the nucleotide
      polymorphism. In this species, the 5.8S ribosomal gene (5.8S) showed scarce
      polymorphism. At the species level, maximum parsimony and maximum likelihood
      analyses revealed that ITS1 and ITS2 may be suitable to reconstruct Ensis
      phylogenetic relationships. Finally, the evolutionary models that best fit the
      long-term evolution of Ensis ITS1-5.8S-ITS2 are discussed. A mixed process of
      concerted evolution, birth-and-death evolution, and selection is chosen as an
      option that may reconcile the long-term evolution of Ensis ITS1-5.8S-ITS2 and 5S
      ribosomal DNA.

PMID- 20130747
TI  - Identification of new winter wheat - winter barley addition lines (6HS and 7H)
      using fluorescence in situ hybridization and the stability of the whole
      'Martonvasari 9 kr1' - 'Igri' addition set.
AB  - A previous paper reported the development of disomic addition lines (2H, 3H, 4H,
      and 1HS isochromosomic) from hybrids between the winter wheat 'Martonvasari 9
      kr1' and the two-rowed winter barley cultivar 'Igri'. The present paper describes
      the isolation of two new additions, the 7H disomic and 6HS ditelosomic additions,
      using fluorescence in situ hybridization with the repetitive DNA probes Afa
      family and HvT01. The identification of the barley chromosomes in the wheat
      genome was confirmed with simple sequence repeat markers. The morphological
      characterization of the new addition lines is also discussed. Studies of the
      genetic stability of the whole set (2H, 3H, 4H, 7H, 1HS iso, 6HS) of
      'Martonvasari 9 kr1' - 'Igri' additions revealed that the most stable disomic
      additions are 2H and 3H and the most unstable line is the 1HS isochromosomic
      addition.

PMID- 20130748
TI  - Identification and molecular characterization of a sex chromosome rearrangement
      causing a soft and pliable (spli) larval body phenotype in the silkworm, Bombyx
      mori.
AB  - We carried out genetic and cytogenetic analyses of X-ray-induced deleterious Z
      chromosomes that result in a soft and pliable (spli) phenotype in the silkworm,
      Bombyx mori. In a B. mori strain with a spli phenotype, we found the Z chromosome
      broken between the sch (1-21.5) and od (1-49.6) loci. We also found a chromosomal
      fragment bearing a fifth-chromosome locus for egg and eye pigmentation fused to a
      Z chromosome fragment. By means of fluorescence in situ hybridization using
      bacterial artificial chromosome clones as probes, we confirmed that the fused
      chromosome is composed of a fragment of chromosome 5 and a fragment of the Z
      chromosome. Moreover, a predicted gene, GA002017, the Bombyx ortholog of the
      Drosophila gene acj6 (Bmacj6), was completely deleted by the Z chromosome
      breakage event. The relationship between Bmacj6 and the spli phenotype is
      discussed.

PMID- 20130749
TI  - Microsatellites in Brassica unigenes: relative abundance, marker design, and use
      in comparative physical mapping and genome analysis.
AB  - Microsatellites present in the transcribed regions of the genome have the
      potential to reveal functional diversity. Unigene sequence databases are the
      sources of such genic microsatellites with unique flanking sequences and genomic
      locations even in complex polyploids. The present study was designed to assay the
      unigenes of Brassica napus and B. rapa for various microsatellite repeats, and to
      design markers and use them in comparative genome analysis and study of
      evolution. The average frequency of microsatellites in Brassica unigenes was one
      in every 7.25 kb of sequence, as compared with one in every 8.57 kb of sequence
      in Arabidopsis thaliana. Trinucleotide motifs coding for serine and the
      dinucleotide motif GA were most abundant. We designed 2374 and 347 unigene-based
      microsatellite (UGMS) markers including 541 and 58 class I types in B. napus and
      B. rapa, respectively, and evaluated their use across diverse species and genera.
      Most of these markers (93.3%) gave successful amplification of target
      microsatellite motifs, which was confirmed by sequencing. Interspecific
      polymorphism between B. napus and B. rapa detected in silico for the UGMS markers
      was 4.16 times higher in 5' untranslated regions than in coding sequences.
      Physical anchoring of Brassica UGMS markers on the A. thaliana genome indicated
      their significance in studying the evolutionary history of A. thaliana genomic
      duplications in relation to speciation. Comparative physical mapping identified
      85% of Brassica unigenes as single copy and gave clues for the presence of
      conserved primordial gene order. Complex chromosomal rearrangements such as
      inversions, tandem and segmental duplications, and insertions/deletions were
      evident between A. thaliana and B. rapa genomes. The results obtained have
      encouraging implications for the use of UGMS markers in comparative genome
      analysis and for understanding evolutionary complexities in the family
      Brassicaceae.

PMID- 20130750
TI  - Evolutionary distribution of light-harvesting complex-like proteins in
      photosynthetic eukaryotes.
AB  - Light-harvesting-like (LIL) proteins are low-molecular-mass membrane proteins
      related to the light-harvesting complexes, which form the dominant antenna system
      in most photosynthetic eukaryotes. To analyze the LIL protein family, we mined a
      number of publicly available databases to identify members of this family in a
      broad range of organisms. LIL proteins are diverse, having one to three predicted
      transmembrane helices. One- and two-helix LIL proteins were found in all the
      major photosynthetic eukaryote lineages (glaucophytes, red algae, and green
      algae) and are particularly well conserved in the green algae and land plants. In
      most cases, however, these proteins are not conserved between major lineages, and
      in some cases appear to have evolved independently. Three-helix LIL proteins are
      well conserved within the gymnosperms and angiosperms, but are much more
      divergent, and have been duplicated multiple times, in the green algae and
      bryophytes. We also identified a novel LIL protein in two Micromonas strains that
      contains a fourth hydrophobic region. This analysis identifies conserved members
      of the LIL protein family, signifying their importance to photosynthetic
      eukaryotes. It also indicates that classification of these proteins based on
      structural characteristics alone inadequately reflects the evolutionary history
      observed in this complex protein family.

PMID- 20130751
TI  - Integration of growth hormone gene constructs in transgenic strains of coho
      salmon (Oncorhynchus kisutch) at centromeric or telomeric sites.
AB  - Very little information is currently available regarding the sites of integration
      of transgenes in genetically engineered fish. We examined the chromosomal
      location of growth hormone gene constructs containing GH1 in three different
      strains of transgenic coho salmon produced by microinjection into pronuclei of
      fertilized eggs. The constructs were labeled and used as probes in fluorescence
      in situ hybridization experiments on chromosome preparations from the M77,
      MT5750A, and H3D0474 strains of transgenic coho salmon. The constructs were
      localized at 1-3 different sites in different strains. In the M77 strain the
      construct was found at a single centromeric site on a medium-sized metacentric
      chromosome, while in the MT5750A strain, the construct was found at a single
      telomeric site on the short arm of chromosome pair 21, a subtelocentric
      chromosome with a large band of repetitive DNA on the short arm. In the H3D0474
      strain, the construct was found at telomeric sites on the long arms of three
      metacentric chromosomes that appear to represent one pair of homologous
      chromosomes and one chromosome containing the homeologous long arm (recently
      duplicated chromosome arm) corresponding to the long arm of the first pair. This
      suggests transfer of the construct may have occurred by homologous and
      homeologous crossing over. All of the constructs incorporated at restricted sites
      characterized by the presence of tandem DNA repeats.

PMID- 20130752
TI  - Development of a Microelectrode Array Sensing Platform for Combination
      Electrochemical and Spectrochemical Aqueous Ion Testing.
AB  - A microelectrode array sensor platform was designed and fabricated to increase
      diversity, flexibility, and versatility of testing capabilities over that of
      traditionally reported sensor platforms. These new sensor platforms consist of 18
      individual addressable microelectrodes, photolithography fabricated, that employ
      a glass base substrate and a resist polymer layer that acts as an insulating
      agent to protect the circuitry and wiring of the sensor from undesired solution
      interactions. Individually addressable microelectrodes increase diversity by
      allowing isolated electrochemical testing between electrodes, global array
      testing, or some combination of electrodes to perform electrochemical methods.
      Furthermore, because of the optical transparency of the glass base substrate and
      the resist mask layer, along with the small size of the electrode array,
      spectrochemical analysis is possible within the sample area that acts as
      electrochemical cell and cuvette, while the microelectrode array passively
      resides within the optical path length during spectrochemical testing. This
      unique arrangement offers improved testing possibilities for various
      applications, including simultaneous electrochemical and spectrochemical analysis
      in environmental testing, identification or quantification of possible species
      for bioavailability in the biotechnology field, and process control in industrial
      applications. Electrochemical characteristics and spectrochemcial use of the
      sensor platform are proven with potassium ferricyanide, an electrochemical
      standard analyte, and electrochemical measurements are compared against a
      commercially available working electrode of similar size. Additionally, the
      electrochemical method of differential pulse anodic stripping voltammetry is
      performed with the sensor platform to detect copper and lead heavy metal ions in
      aqueous solution, demonstrating the potential for use with environmental samples.

PMID- 20130753
TI  - Free swelling and confined smart hydrogels for applications in chemomechanical
      sensors for physiological monitoring.
AB  - We investigate thin films of "smart" polymer hydrogels used to convert miniature
      pressure sensors into novel chemomechanical sensors. In this versatile sensing
      approach, a smart hydrogel is confined between a porous membrane and the
      diaphragm of a piezoresistive pressure transducer. An increase in the
      environmental analyte concentration, as sensed through the pores of the membrane,
      is detected by measuring the change in pressure exerted by the hydrogel on the
      pressure transducer diaphragm. We compare the response of such a sensor with the
      response of a free-swelling hydrogel identical to the one used within the sensor.
      The sensor and the free hydrogel are observed to have comparable mean response
      times. However, the time-dependent response curve of the sensor, unlike that of
      the free hydrogel, is highly asymmetric between swelling and deswelling, with a
      smaller time constant for deswelling. We also investigate novel methods for
      increasing sensor sensitivity, such as use of a two-layer membrane with a
      nanoporous polymer inner layer, and pre-loading of the hydrogel under pressure.
      In ionic strength response tests, use of an inner membrane increases sensor
      sensitivity without increasing mean response time, an effect that varies with
      membrane water fraction.

PMID- 20130754
TI  - Sequential Reinstatement of Neocortical Activity during Slow Oscillations Depends
      on Cells' Global Activity.
AB  - During Slow Wave Sleep (SWS), cortical activity is dominated by endogenous
      processes modulated by slow oscillations (0.1-1 Hz): cell ensembles fluctuate
      between states of sustained activity (UP states) and silent epochs (DOWN states).
      We investigate here the temporal structure of ensemble activity during UP states
      by means of multiple single unit recordings in the prefrontal cortex of naturally
      sleeping rats. As previously shown, the firing rate of each PFC cell peaks at a
      distinct time lag after the DOWN/UP transition in a consistent order. We show
      here that, conversely, the latency of the first spike after the UP state onset
      depends primarily on the session-averaged firing rates of cells (which can be
      considered as an indirect measure of their intrinsic excitability). This latency
      can be explained by a simple homogeneous process (Poisson model) of cell firing,
      with sleep averaged firing rates employed as parameters. Thus, at DOWN/UP
      transitions, neurons are affected both by a slow process, possibly originating in
      the cortical network, modulating the time course of firing for each cell, and by
      a fast, relatively stereotyped reinstatement of activity, related mostly to
      global activity levels.

PMID- 20130755
TI  - Equilibrium and Response Properties of the Integrate-and-Fire Neuron in Discrete
      Time.
AB  - The integrate-and-fire neuron with exponential postsynaptic potentials is a
      frequently employed model to study neural networks. Simulations in discrete time
      still have highest performance at moderate numerical errors, which makes them
      first choice for long-term simulations of plastic networks. Here we extend the
      population density approach to investigate how the equilibrium and response
      properties of the leaky integrate-and-fire neuron are affected by time
      discretization. We present a novel analytical treatment of the boundary condition
      at threshold, taking both discretization of time and finite synaptic weights into
      account. We uncover an increased membrane potential density just below threshold
      as the decisive property that explains the deviations found between simulations
      and the classical diffusion approximation. Temporal discretization and finite
      synaptic weights both contribute to this effect. Our treatment improves the
      standard formula to calculate the neuron's equilibrium firing rate. Direct
      solution of the Markov process describing the evolution of the membrane potential
      density confirms our analysis and yields a method to calculate the firing rate
      exactly. Knowing the shape of the membrane potential distribution near threshold
      enables us to devise the transient response properties of the neuron model to
      synaptic input. We find a pronounced non-linear fast response component that has
      not been described by the prevailing continuous time theory for Gaussian white
      noise input.

PMID- 20130756
TI  - Neuroplasticity associated with tactile language communication in a deaf-blind
      subject.
AB  - A long-standing debate in cognitive neuroscience pertains to the innate nature of
      language development and the underlying factors that determine this faculty. We
      explored the neural correlates associated with language processing in a unique
      individual who is early blind, congenitally deaf, and possesses a high level of
      language function. Using functional magnetic resonance imaging (fMRI), we
      compared the neural networks associated with the tactile reading of words
      presented in Braille, Print on Palm (POP), and a haptic form of American Sign
      Language (haptic ASL or hASL). With all three modes of tactile communication,
      indentifying words was associated with robust activation within occipital
      cortical regions as well as posterior superior temporal and inferior frontal
      language areas (lateralized within the left hemisphere). In a normally sighted
      and hearing interpreter, identifying words through hASL was associated with left
      lateralized activation of inferior frontal language areas however robust
      occipital cortex activation was not observed. Diffusion tensor imaging -based
      tractography revealed differences consistent with enhanced occipital-temporal
      connectivity in the deaf-blind subject. Our results demonstrate that in the case
      of early onset of both visual and auditory deprivation, tactile-based
      communication is associated with an extensive cortical network implicating
      occipital as well as posterior superior temporal and frontal associated language
      areas. The cortical areas activated in this deaf-blind subject are consistent
      with characteristic cortical regions previously implicated with language.
      Finally, the resilience of language function within the context of early and
      combined visual and auditory deprivation may be related to enhanced connectivity
      between relevant cortical areas.

PMID- 20130757
TI  - Vibration-processing interneurons in the honeybee brain.
AB  - The afferents of the Johnston's organ (JO) in the honeybee brain send their axons
      to three distinct areas, the dorsal lobe, the dorsal subesophageal ganglion (DL
      dSEG), and the posterior protocerebral lobe (PPL), suggesting that vibratory
      signals detected by the JO are processed differentially in these primary sensory
      centers. The morphological and physiological characteristics of interneurons
      arborizing in these areas were studied by intracellular recording and staining.
      DL-Int-1 and DL-Int-2 have dense arborizations in the DL-dSEG and respond to
      vibratory stimulation applied to the JO in either tonic excitatory, on-off-phasic
      excitatory, or tonic inhibitory patterns. PPL-D-1 has dense arborizations in the
      PPL, sends axons into the ventral nerve cord (VNC), and responds to vibratory
      stimulation and olfactory stimulation simultaneously applied to the antennae in
      long-lasting excitatory pattern. These results show that there are at least two
      parallel pathways for vibration processing through the DL-dSEG and the PPL. In
      this study, Honeybee Standard Brain was used as the common reference, and the
      morphology of two types of interneurons (DL-Int-1 and DL-Int-2) and JO afferents
      was merged into the standard brain based on the boundary of several neuropiles,
      greatly supporting the understanding of the spatial relationship between these
      identified neurons and JO afferents. The visualization of the region where the JO
      afferents are closely appositioned to these DL interneurons demonstrated the
      difference in putative synaptic regions between the JO afferents and these DL
      interneurons (DL-Int-1 and DL-Int-2) in the DL. The neural circuits related to
      the vibration-processing interneurons are discussed.

PMID- 20130758
TI  - Cueless blindsight.
AB  - The term blindsight describes the non-reflexive visual functions that remain or
      recover in fields of absolute cortical blindness. As visual stimuli confined to
      such fields are subjectively invisible, they are customarily announced by visible
      or audible cues that inform the patients when to respond. The pervasive use of
      cueing has spawned the widely held assumption that sight and blindsight differ in
      that only blindsight requires cueing. To test this assumption, we measured
      detection of auditorily cued and un-cued stimuli in three hemianopic patients.
      Stimuli fell onto the photosensitive retina of the subjectively blind field, onto
      the objectively blind optic disc, and, in one patient, into a region where they
      evoked impoverished conscious sight. Regardless of whether cues were given,
      performance was highly significant in the latter region of poor sight, clearly
      above chance in the subjectively blind field, and random in the optic disc
      control condition. Moreover, cues enhanced detection only in the relatively blind
      field. Showing that blindsight performance persists when cues are omitted, the
      results imply that non-reflexive responses can be initiated in the absence of
      both stimulus awareness and perceptible cues.

PMID- 20130760
TI  - Discordant Tasks and Motor Adjustments Affect Interactions between Adaptations to
      Altered Kinematics and Dynamics.
AB  - Motor control and adaptation are multi-determinate processes with complex
      interactions. This is reflected for example in the ambiguous nature of
      interactions during sequential adaptation of reaching under kinematics and
      dynamics perturbations. It has been suggested that perturbations based on the
      same kinematic parameter interfere. Others posited that opposing motor
      adjustments underlie interference. Here, we examined the influence of
      discordances in task and in motor adjustments on sequential adaptations to
      visuomotor rotation and viscous force field perturbations. These two factors -
      perturbation direction and task discordance - have been examined separately by
      previous studies, thus the inherent difficulty to identify the roots of
      interference. Forty-eight human subjects adapted sequentially to one or two types
      of perturbations, of matched or conflicting directions. We found a gradient of
      interaction effects based on perturbation direction and task discordance.
      Perturbations of matched directions showed facilitation while perturbations of
      opposite directions, which required opposing motor adjustments, interfered with
      each other. Further, interaction effects increased with greater task discordance.
      We also found that force field and visuomotor rotation had mutual anterograde and
      retrograde effects. However, we found independence between anterograde and
      retrograde interferences between similar tasks. The results suggest that the
      newly acquired internal models of kinematic and dynamic perturbations are not
      independent but they share common neuronal resources and interact between them.
      Such overlap does not necessarily imply competition of resources. Rather, our
      results point to an additional principle of sensorimotor adaptation allowing the
      system to tap or harness common features across diverse sensory inputs and task
      contexts whenever available.

PMID- 20130759
TI  - Early Visually Evoked Electrophysiological Responses Over the Human Brain (P1,
      N170) Show Stable Patterns of Face-Sensitivity from 4 years to Adulthood.
AB  - Whether the development of face recognition abilities truly reflects changes in
      how faces, specifically, are perceived, or rather can be attributed to more
      general perceptual or cognitive development, is debated. Event-related potential
      (ERP) recordings on the scalp offer promise for this issue because they allow
      brain responses to complex visual stimuli to be relatively well isolated from
      other sensory, cognitive and motor processes. ERP studies in 5- to 16-year-old
      children report large age-related changes in amplitude, latency (decreases) and
      topographical distribution of the early visual components, the P1 and the
      occipito-temporal N170. To test the face specificity of these effects, we
      recorded high-density ERPs to pictures of faces, cars, and their phase-scrambled
      versions from 72 children between the ages of 4 and 17, and a group of adults. We
      found that none of the previously reported age-dependent changes in amplitude,
      latency or topography of the P1 or N170 were specific to faces. Most importantly,
      when we controlled for age-related variations of the P1, the N170 appeared
      remarkably similar in amplitude and topography across development, with much
      smaller age-related decreases in latencies than previously reported. At all ages
      the N170 showed equivalent face-sensitivity: it had the same topography and right
      hemisphere dominance, it was absent for meaningless (scrambled) stimuli, and
      larger and earlier for faces than cars. The data also illustrate the large amount
      of inter-individual and inter-trial variance in young children's data, which
      causes the N170 to merge with a later component, the N250, in grand-averaged
      data. Based on our observations, we suggest that the previously reported "bi-fid"
      N170 of young children is in fact the N250. Overall, our data indicate that the
      electrophysiological markers of face-sensitive perceptual processes are present
      from 4 years of age and do not appear to change throughout development.

PMID- 20130761
TI  - Heme Oxygenase Contributes to Alleviate Salinity Damage in Glycine max L. Leaves.
AB  - Plants are frequently subjected to different kinds of stress, such as salinity
      and, like other organisms, they have evolved strategies for preventing and
      repairing cellular damage caused by salt stress. Glycine max L. plants were
      subjected to different NaCl concentrations (0-200 mM) for 10 days. Treatments
      with 100 and 200 mM NaCl induced ion leakage and lipid peroxidation augmentation,
      loss in chlorophyll content, and accumulation of O(2) (*-) and H(2)O(2). However,
      50 mM NaCl did not modify these parameters, which remains similar to control
      values. Catalase, superoxide dismutase, and heme oxygenase (HO-1) activities and
      gene expressions were increased under 100 mM NaCl, while no differences were
      observed with respect to controls under 50 mM salt. Treatment with 200 mM NaCl
      caused a diminution in the enzyme activities and gene expressions. Results here
      reported let us conclude that HO also plays a leading role in the defense
      mechanisms against salinity.

PMID- 20130762
TI  - A targeted parathyroidectomy using guide wire technique in a pregnant patient
      with primary hyperparathyroidism.
AB  - Primary hyperparathyroidism may cause fetal demise in pregnant patients if prompt
      diagnosis and treatment is not initiated. The paper describes a novel guide wire
      technique for a targeted parathyroidectomy, which may reduce the risk to mother
      and fetus and be useful in other related circumstances.

PMID- 20130763
TI  - Outcome and prognostic indicators of patients with hematopoietic stem cell
      transplants admitted to the intensive care unit.
AB  - The prognosis of patients with hematopoietic stem cell transplants (HSCTs) who
      require admission to the intensive care unit (ICU) has been regarded as extremely
      poor. We sought to re-evaluate recent outcomes and predictive factors in a
      retrospective cohort study. Among the 605 adult patients that received an HSCT
      between 2001 and 2006, 154 required admission to the ICU. Of these, 47% were
      discharged from the ICU, 36% were discharged from the hospital, and 19% survived
      6 months. Allogeneic transplant, mechanical ventilation, vasopressor-use, and
      neutropenia were each associated with increased mortality, and the mortality of
      patients with all four characteristics was 100%. Hemodialysis was also associated
      with increased mortality in a Kaplan-Meier analysis but did not appear important
      in a multivariate tree analysis. A final Cox model confirmed that allogeneic
      transplant, mechanical ventilation, and vasopressor-use were each independent
      risk factors for mortality in the 6 months following ICU admission.

PMID- 20130764
TI  - Effects of cytochrome p450 inhibitors on itraconazole and fluconazole induced
      cytotoxicity in hepatocytes.
AB  - Itraconazole and fluconazole have been reported to induce hepatotoxicity in
      patients. The present study was designed to investigate the role of cytochrome
      P450 inhibitors, SKF 525A, and curcumin pretreatment on the cytotoxicity of
      antifungal drugs fluconazole and itraconazole. For 3 consecutive days, female
      rats were administered daily SKF 525A or curcumin (5 and 25 mg/kg). Control rats
      received an equivalent amount of dosed vehicle. The animals were anaesthetized 24
      hours after receiving the last dose for liver perfusion. Hepatocytes were then
      exposed to various concentrations of antifungal drugs. In vitro incubation of
      hepatocytes with itraconazole revealed significantly lower viability when
      compared to fluconazole as assessed by lactate dehydrogenase, aspartate
      aminotransferase and alanine aminotransferase activities. The cytotoxicity of
      itraconazole was enhanced when incubated with hepatocytes pretreated with SKF
      525A. SKF 525A had no effects on the cytotoxicity of fluconazole. Curcumin failed
      to either increase or decrease the cytotoxicity of both antifungal drugs. ATP
      levels also showed significant decrease in both itraconazole and fluconazole
      incubated hepatocytes. However, SKF 525A pretreated hepatocytes had significantly
      lower ATP levels after itraconazole incubations. Collectively, these results
      confirm the involvement of cytochrome P450 in the cytoprotection in itraconazole
      induced hepatocyte toxicity. Differences of the effects of SKF 525A on the
      cytotoxicity induced by itraconazole and fluconazole may be due to the
      differences on the metabolism of each antifungal drug in vivo.

PMID- 20130765
TI  - Cellular therapy for repair of cardiac damage after acute myocardial infarction.
AB  - Cardiovascular diseases, particularly acute myocardial infarction, are the
      leading causes of death worldwide. Important advances have been made in the
      secondary treatment for cardiovascular diseases such as heart transplantation and
      medical and surgical therapies. Although these therapies alleviate symptoms, and
      may even improve survival, none can reverse the disease process and directly
      repair the lasting damage. Thus, the cure of cardiovascular diseases remains a
      major unmet medical need. Recently, cellular therapy has been proposed as a
      candidate treatment for this. Many stem and progenitor cell populations have each
      been suggested as a potential basis for such therapy. This review assesses some
      of the more notable exogenous adult cell candidates and provides insights into
      the mechanisms by which they may mediate improvement in cardiac function
      following acute myocardial infarction. Research into the cellular therapy field
      is of great importance for the further planning of clinical trials for cardiac
      cellular myoplasty.

PMID- 20130766
TI  - Analysis of auditory measures in normal hearing young male adult cigarette
      smokers using multiple variable selection methods with predictive validation
      assessments.
AB  - Studies have shown that cigarette smoking is a risk factor for hearing loss;
      however, no information is available on auditory preclinical indicators in young
      chronic cigarette smokers. Cigarette smoking involves exposure to many harmful
      chemicals including carbon monoxide (CO). In this study, the CO level in 16 young
      normal hearing male chronic smokers was measured with a CO monitor, and was used
      as the outcome measure. Subjects were administered a battery of audiological
      tests that included behavioral and electrophysiologic measures. The goal was to
      investigate which auditory test measures can be used as potential predictors of
      the outcome measure. Using ordinary least squares estimation procedures with best
      subsets selection and bootstrapped stepwise variable selection procedures, an
      optimal predictive multiple linear regression model was selected. Results of this
      approach indicated that auditory brainstem response peak V amplitudes and
      distortion product otoacoustic emissions had the highest predictive value and
      accounted for most of the variability.

PMID- 20130767
TI  - Percutaneous Transhepatic Bile Duct Ablation with n-Butyl Cyanoacrylate in the
      Treatment of a Biliary Complication after Split Liver Transplantation.
AB  - Biliary complications continue to be a major cause of morbidity after split-liver
      transplantation (SLT). In this report we describe an uncommon late biliary
      complication. One year after SLT the patient showed an intrahepatic bile dicy
      dilatation with severe cholangitis episodes. The segmentary bile duct of hepatic
      segment VI-VII draining in the left duct was unidentified and tied at the time of
      the in situ split-liver procedure. We perform a permanent obliteration of the
      dilated intrahepatic ducts by a percutaneous embolization using an n-butyl
      cyanoacrylate (NABC). The management of biliary complications after SLT requires
      a multidisciplinary approach. The use of NBCA in obliteration of a dilated bile
      duct seems to be a safe procedure with good results providing a less invasive
      option than hepatic resection and decreasing the morbidity associated with
      chronic external biliary drainage. Further studies are needed to determine
      whether this approach is effective and safe and whether it could reduce hospital
      stay and cost.

PMID- 20130768
TI  - Selective vulnerability of the cochlear Basal turn to acrylonitrile and noise.
AB  - Exposure to acrylonitrile, a high-production industrial chemical, can promote
      noise-induced hearing loss (NIHL) in the rat even though this agent does not
      itself produce permanent hearing loss. The mechanism by which acrylonitrile
      promotes NIHL includes oxidative stress as antioxidant drugs can partially
      protect the cochlea from acrylonitrile + noise. Acrylonitrile depletes
      glutathione levels while noise can increase the formation of reactive oxygen
      species. It was previously noted that the high-frequency or basal turn of the
      cochlea was particularly vulnerable to the combined effects of acrylonitrile and
      noise when the octave band noise (OBN) was centered at 8 kHz. Normally, such a
      noise would be expected to yield damage at a more apical region of the cochlea.
      The present study was designed to determine whether the basal cochlea is
      selectively sensitive to acrylonitrile or whether, by adjusting the frequency of
      the noise band, it would be possible to control the region of the auditory
      impairment. Rats were exposed to one of three different OBNs centered at
      different frequencies (4 kHz, 110 dB and 8 or 16 kHz at 97 dB) for 5 days, with
      and without administration of acrylonitrile (50 mg/kg/day). The noise was set to
      cause limited NIHL by itself. Auditory function was monitored by recording
      distortion products, by compound action potentials, and by performing cochlear
      histology. While the ACN-only and noise-only exposures induced no or little
      permanent auditory loss, the three exposures to acrylonitrile + noise produced
      similar auditory and cochlear impairments above 16 kHz, despite the fact that the
      noise exposures covered 2 octaves. These observations show that the basal cochlea
      is much more sensitive to acrylonitrile + noise than the apical partition. They
      provide an initial basis for distinguishing the pattern of cochlear injury that
      results from noise exposure from that which occurs due to the combined effects of
      noise and a chemical contaminant.

PMID- 20130769
TI  - Optimum combination of insulin-transferrin-selenium and fetal bovine serum for
      culture of rabbit articular chondrocytes in three-dimensional alginate scaffolds.
AB  - Fetal bovine serum (FBS) has been reported to affect chondrocyte biosynthesis in
      monolayer culture. Insulin-Transferrin-Selenium (ITS) was investigated as a
      partial replacement for FBS during in vitro culture of rabbit articular
      chondrocytes in three-dimensional alginate scaffold. Chondrocyte-seeded alginate
      hydrogels were cultured in Dulbecco's modified Eagle's medium plus 10% FBS, 1%
      ITS plus 2% FBS, 1% ITS plus 4% FBS, or 1% ITS plus 8% FBS. At designed time
      point, the Chondrocyte-seeded alginate hydrogels were harvested and evaluated
      with histological staining, immunohistochemistry, and quantitative gene
      expression analysis. Viable cell density and cell division were also evaluated.
      Chondrocytes biosynthesis and cell division in 1% ITS with 2% FBS medium were
      similar to that in medium added with 10% FBS. For a total culture of 3 weeks,
      phenotypic gene expression in chondrocyte-seeded hydrogels was maintained at high
      levels in medium with 1% ITS plus 2% FBS, while it was decreased to varying
      degrees in the other groups. In conclusion, with 1% ITS, medium with 2% FBS could
      promote chondrocyte biosynthesis and cell division, and prevented cell
      dedifferentiation in three-dimensional alginate scaffolds.

PMID- 20130770
TI  - Congenital epulis: a case report and estimation of incidence.
AB  - Congenital Epulis, also known as Neumann's tumour, is a rare congenital growth
      affecting the gingival mucosa of neonates. It is benign condition, seen more
      frequently in females, with multiple Epuli occurring in only 10% of cases. The
      cause and origin of Congenital Epulis remains unclear. In this article we present
      a case report of an otherwise healthy female neonate with two Congenital Epuli
      arising from the upper and lower gingival margin, which were successfully treated
      with surgical excision. We also present a review of the literature and an
      estimation of the incidence of Congenital Epulis based on our institutions
      figures, of 0.0006% (upper 95% confidence interval: 0.0035%).

PMID- 20130771
TI  - On the toxicity of therapeutically used nanoparticles: an overview.
AB  - Human beings have been exposed to airborne nanosized particles throughout their
      evolutionary stages, and such exposures have increased dramatically over the last
      century. The rapidly developing field of nanotechnology will result in new
      sources of this exposure, through inhalation, ingestion, and injection. Although
      nanomaterials are currently being widely used in modern technology, there is a
      serious lack of information concerning the human health and environmental
      implications of manufactured nanomaterials. Since these are relatively new
      particles, it is necessary to investigate their toxicological behavior. The
      objective of this review was to trace the cellular response to nanosized particle
      exposure. Therapeutic application of selected nanoparticles together with their
      range of toxic doses was also reviewed. Effect of therapeutically used
      nanoparticles on cell membrane, mitochondrial function, prooxidant/antioxidant
      status, enzyme leakage, DNA, and other biochemical endpoints was elucidated. This
      paper highlights the need for caution during the use and disposal of such
      manufactured nanomaterials to prevent unintended environmental impacts.

PMID- 20130772
TI  - A comprehensive review of immunosuppression used for liver transplantation.
AB  - Since liver transplantation was approved for the treatment of end stage liver
      disease, calcineurin inhibitors (CNI's) have played a critical role in the
      preservation of allograft function. Unfortunately, these medications cause a
      variety of Side effects such as diabetes, hypertension and nephrotoxicity which
      in turn result in significant morbidity and reduced quality of life. A variety of
      newer immunosuppressants have been evaluated over the last decade in an attempt
      to either substitute for CNI's or use with reduced dose CNI's while still
      preserving allograft function However, current data does not recommend complete
      cessation of CNI's due to unacceptably high rates of allograft rejection. As
      these medications have their own unique adverse effects, a careful assessment on
      their risks and benefits is essential, particularly when additive or synergistic
      effects with CNI's may occur. Furthermore, the impact of these newer medications
      on the risk of hepatitis C recurrence and progression remains to be elucidated.
      Controlled trials are urgently required to assist transplant physicians with
      choosing the optimum immunosuppressive regimen for their patients. This review
      will discuss commonly used immunosuppressants prescribed in liver
      transplantation, emerging therapties and where appropriate, the impact of these
      medications on the recurrence of hepatitis C after liver transplantation.

PMID- 20130773
TI  - Molecular mechanisms involved in mesenchymal stem cell migration to the site of
      acute myocardial infarction.
AB  - Mesenchymal stem cells or multipotent mesenchymal stromal cells (both referred to
      as MSC) have been shown in some studies to have a beneficial effect on myocardial
      recovery after infarct. Current strategies for MSC delivery to heart involve
      intravenous, intraarterial, and intramuscular delivery. Different routes of MSC
      delivery and a lack of knowledge of the mechanisms that MSC utilise to migrate in
      vivo has most likely led to the marked variations in results that have been
      found. This review aims to summarise the current knowledge of MSC migratory
      mechanisms and looks to future methods of MSC manipulation prior to delivery in
      order to enhance MSC migration and engraftment.

PMID- 20130774
TI  - Concentrations of h1-receptor antagonist in the human nasal mucosa.
AB  - Aims. To measure blood and tissue concentrations of the H1-receptor antagonist,
      bepotastine besilate (BB). Methods. Participants included 14 men and six women,
      whose age ranged from 13 to 76 years, with chronic rhinosinusitis, who underwent
      endoscopic sinus surgery at our university hospital. Among them, 10 participants
      had allergic rhinitis (AR) (Group I), and others did not have AR (Group II).
      Nasal mucosa and blood were collected 55 to 130 minutes after oral administration
      of BB 10 mg. Concentrations of the agent in the serum and nasal mucosa were
      measured by high-performance liquid chromatography. Results. Concentrations of BB
      of the serum in Group I and II were 98 +/- 32 ng/mL and 112 +/- 39 ng/mL. Those
      of the nasal mucosa tissue in Groups I and II were 101 +/- 36 ng/g and 132 +/- 44
      ng/g. There was no significant difference in the values of concentration of BB
      between the serum and the nasal mucosa in either Group I or II (P = .757 and P =
      .2662, resp., Paired t-test). Conclusion. This preliminary study is considered
      the first report on the concentration of H1-receptor antagonists in nasal mucosa.
      The prompt absorption and transition to the nasal mucosa of BB seems to have an
      effect on allergic rhinitis.

PMID- 20130775
TI  - A fatal waterborne outbreak of pesticide poisoning caused by damaged pipelines,
      sindhikela, bolangir, orissa, India, 2008.
AB  - Introduction. We investigated a cluster of pesticide poisoning in Orissa.
      Methods. We searched the village for cases of vomiting and sweating on 2 February
      2008. We described the outbreak by time, place, and person. We compared cases
      with controls. Results. We identified 65 cases (two deaths; attack rate: 12 per
      1000; case fatality: 3%). The epidemic curve suggested a point source outbreak,
      and cases clustered close to a roadside eatery. Consumption of water from a
      specific source (odds ratio [OR]: 35, confidence interval [CI]: 13-93) and eating
      in the eatery (OR: 2.3, CI: 1.1-4.7) was associated with illness. On 31 January
      2008, villagers had used pesticides to kill street dogs and had discarded
      leftovers in the drains. Damaged pipelines located beneath and supplying water
      may have aspirated the pesticide during the nocturnal negative pressure phase and
      rinsed it off the next morning in the water supply. Conclusions. Innapropriate
      use of pesticides contaminated the water supply and caused this outbreak.
      Education programs and regulations need to be combined to ensure a safer use of
      pesticides in India.

PMID- 20130776
TI  - Platelet thromboembolism after lung transplantation.
AB  - Lung transplant patients have an increased risk of pulmonary embolism which is
      often associated with hypercoagulability disorders. We present a case of sudden
      death resulting from pulmonary intravascular platelet thromboembolism following a
      single-lung transplant.

PMID- 20130777
TI  - Determinants Present in the Receptor Carboxy Tail Are Responsible for Differences
      in Subtype-Specific Coupling of beta-Adrenergic Receptors to Phosphoinositide 3
      Kinase.
AB  - An agonist-occupied beta(2)-adrenergic receptor (beta(2)-AR) recruits G protein
      receptor kinase-2 (GRK2) which is recruited to the membrane. Thus, the physical
      proximity of activated beta(2)-AR and PI-3K allows the activation of the latter.
      In contrast, it has been observed that the beta(1)-AR is unable to activate the
      PI-3K/Akt pathway. We hypothesized that the difference might be due to molecular
      determinants present in the carboxy termini of the two beta-AR subtypes. Using
      transiently transfected HEK 293 cells expressing either beta(1)- or beta(2)-AR,
      we also observed that in presence of an agonist, beta(2)-AR, but not beta(1)-AR,
      is able to activate the PI-3K/Akt pathway. Switching the seventh transmembrane
      domain and the carboxy tail between the two receptors reverses this phenotype;
      that is, beta(1) x beta(2)-AR can activate the PI-3K/Akt pathway whereas beta(2)
      x beta(1)-AR cannot. Pretreatment with pertussis toxin abolished the activation
      of PI-3K by beta(2)- or beta(1) x beta(2)-AR stimulation. Ligand-mediated
      internalization of the beta(2)-AR induced by a 15-minute stimulation with agonist
      was abolished in the presence of a dominant negative of PI-3K or following
      pertussis toxin pretreatment. These results indicate that the subtype-specific
      differences in the coupling to PI-3K/Akt pathway are due to molecular
      determinants present in the carboxy tail of the receptor and further that beta(2)
      AR activates PI-3K via a pertussis toxin-sensitive mechanism.

PMID- 20130778
TI  - Regression of Hypervascular Nodules in a Patient with Wilson's Disease Awaiting
      Liver Transplantation.
AB  - This paper describes the regressive course over one year of hypervascular nodules
      in a patient with Wilson's disease. CT revealed multiple, enhancing nodules (up
      to 3 cm in diameter) detected in the liver in the early arterial phase after the
      administration of intravenous contrast material. Most of these nodules became
      isodense in the portal venous phase. After one year of efficient therapy
      combining d-penicillamine and zinc acetate, most of the nodules had disappeared,
      while the liver contours had become more regular. To our knowledge, the
      regression of large hypervascular nodules has not previously been reported in
      patients with Wilson's disease.

PMID- 20130779
TI  - Cytotoxic Effect of the Genus Sinularia Extracts on Human SCC25 and HaCaT Cells.
AB  - Soft corals of the genus Sinularia are being increasingly adopted to treat a wide
      variety of disease processes. However, the mechanism underlying its activity
      against human oral cancer cells is poorly understood. This study evaluates the
      cyototoxicity effects of the genus Sinularia extracts (S. grandilobata, S. parva,
      S. triangula, S. scabra, S. nanolobata and S. gibberosa) by SCC25 and HaCaT
      cells. The cell adhesion assay indicates that extracts reduce the cell
      attachment. Extracts exhibit a dose-dependent cytotoxic effect using MTS
      assay.Treatment of extracts to observe the morphological alterations in cells,
      membrane blebbing, nuclear condensation, and apoptotic bodies is demonstrated.
      Flow cytometry shows that extracts sensitized the cells in the G(0)/G(1) and
      G(2)/M phases with a concomitant significantly increased sub-G(1) fraction,
      suggesting cell death by apoptosis. Extracts of the genus Sinularia thus
      apparently cause apoptosis of SCC25 and HaCaT cells, and warrant further research
      investigating the possible antioral cancer compounds in these soft corals.

PMID- 20130780
TI  - Cannabis and breastfeeding.
AB  - Cannabis is a drug derived from hemp plant, Cannabis sativa, used both as a
      recreational drug or as medicine. It is a widespread illegal substance, generally
      smoked for its hallucinogenic properties. Little is known about the adverse
      effects of postnatal cannabis exposure throw breastfeeding because of a lack of
      studies in lactating women. The active substance of cannabis is the delta 9
      TetraHydroCannabinol (THC). Some studies conclude that it could decrease motor
      development of the child at one year of age. Therefore, cannabis use and abuse of
      other drugs like alcohol, tobacco, or cocaine must be contraindicated during
      breastfeeding. Mothers who use cannabis must stop breastfeeding, or ask for
      medical assistance to stop cannabis use in order to provide her baby with all the
      benefits of human milk.

PMID- 20130781
TI  - Efficient simulation of the spatial transmission dynamics of influenza.
AB  - Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies
      over-estimated the within-country rate of spatial spread of pandemic influenza.
      As large spatially-resolved data sets are constructed, the need for efficient
      simulation code with which to investigate the spatial patterns of the pandemic
      becomes clear. Here, we describe a significant improvement in the efficiency of
      an individual-based stochastic disease simulation framework that has been used
      for multiple previous studies. We quantify the efficiency of the revised
      algorithm and present an alternative parameterization of the model in terms of
      the basic reproductive number. We apply the model to the population of Taiwan and
      demonstrate how the location of the initial seed can influence spatial incidence
      profiles and the overall spread of the epidemic. Differences in incidence are
      driven by the relative connectivity of alternate seed locations.

PMID- 20130782
TI  - Release of glycoprotein (GP1) from the tegumental surface of Taenia solium by
      phospholipase C from Clostridium perfringens suggests a novel protein-anchor to
      membranes.
AB  - In order to explore how molecules are linked to the membrane surface in larval
      Taenia solium, whole cysticerci were incubated in the presence of phospholipase C
      from Clostridium perfringens (PLC). Released material was collected and analyzed
      in polyacrylamide gels with sodium dodecyl sulfate. Two major bands with apparent
      molecular weights of 180 and 43 kDa were observed. Western blot of released
      material and localization assays in cysticerci tissue sections using antibodies
      against five known surface glycoproteins of T. solium cysticerci indicated that
      only one, previously called GP1, was released. Similar localization studies using
      the lectins wheat-germ-agglutinin and Concanavalin A showed that N-acetyl-D
      glucosamine, N-acetylneuraminic, sialic acid, alphamethyl-D-mannoside, D
      manose/glucose, and N-acetyl-D-glucosamine residues are abundantly present on the
      surface. On the other hand, we find that treatment with PLC releases molecules
      from the surface; they do not reveal Cross Reacting Determinant (CRD), suggesting
      a novel anchor to the membrane for the glycoprotein GP1.

PMID- 20130783
TI  - Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of
      Black Cohosh.
AB  - There are a growing number of cases detailing acute hepatic necrosis in patients
      taking black cohosh (Cimicifuga racemosa), an over-the-counter herbal supplement
      for management of menopausal symptoms. Our aim is to illustrate two cases of
      liver injury following the use of black cohosh characterized by histopathological
      features mimicking autoimmune hepatitis. Both patients reported black cohosh use
      for at least six months and had no evidence of another cause of liver disease.
      Their liver biopsies showed a component of centrilobular necrosis consistent with
      severe drug-induced liver injury. In addition, the biopsies showed
      characteristics of autoimmune-like liver injury with an interface hepatitis
      dominated by plasma cells. Although serum markers for autoimmune hepatitis were
      not particularly elevated, both patients responded to corticosteroids, supporting
      an immune-mediated component to the liver injury. Liver injury following the use
      of black cohosh should be included in the list of differential diagnoses for
      chronic hepatitis with features mimicking autoimmune hepatitis.

PMID- 20130784
TI  - OXavidin for tissue targeting biotinylated therapeutics.
AB  - Avidin is a glycoprotein from hen egg white that binds biotin with very high
      affinity. Here we describe OXavidin, a product containing aldehyde groups,
      obtained by ligand-assisted sugar oxidation of avidin by sodium periodate.
      OXavidin chemically reacts with cellular and tissue proteins through Schiff's
      base formation thus residing in tissues for weeks while preserving the biotin
      binding capacity. The long tissue residence of OXavidin as well as that of
      OXavidin/biotinylated agent complex occurs in normal and neoplastic tissues and
      immunohistochemistry shows a strong and homogenous stromal localization. Once
      localized in tissue/tumor, OXavidin becomes an "artificial receptor" for
      intravenous injected biotin allowing tumor targeting with biotinylated
      therapeutics like radioisotopes or toxins. Moreover, present data also suggest
      that OXavidin might be useful for the homing of biotinylated cells. Overall,
      OXavidin exhibits a remarkable potential for many different therapeutic
      applications.

PMID- 20130785
TI  - Assessment of Confounding Factors Affecting the Tumor Markers SMRP, CA125, and
      CYFRA21-1 in Serum.
AB  - The purpose of this analysis was to evaluate if serum levels of potential tumor
      markers for the diagnosis of malignant mesothelioma and lung cancer are affected
      by confounding factors in a surveillance cohort of workers formerly exposed to
      asbestos. SMRP, CA125, and CYFRA21-1 concentrations were determined in about
      1,700 serum samples from 627 workers formerly exposed to asbestos. The impact of
      factors that could modify the concentrations of the tumor markers was examined
      with linear mixed models. SMRP values increased with age 1.02-fold (95% CI 1.01
      1.03) and serum creatinine concentration 1.32-fold (95% CI 1.20-1.45). Levels
      differed by study centers and were higher after 40 years of asbestos exposure.
      CA125 levels increased with longer storage of the samples. CYFRA21-1 values
      correlated with age 1.02-fold (95% CI 1.01-1.02), serum creatinine 1.21-fold (95%
      CI 1.14-1.30) and varied by study centers due to differences in sample handling.
      Tumor marker concentrations are influenced by subject-related factors, sample
      handling, and storage. These factors need to be taken into account in screening
      routine.

PMID- 20130786
TI  - The Concurrency Hypothesis in Sub-Saharan Africa: Convincing Empirical Evidence
      is Still Lacking. Response to Mah and Halperin, Epstein, and Morris.

PMID- 20130787
TI  - Subsidized Contraception, Fertility, and Sexual Behavior.
AB  - We examine the impact of recent state-level Medicaid policy changes that expanded
      eligibility for family planning services to higher-income women and to Medicaid
      clients whose benefits would expire otherwise. We show that the income-based
      policy change reduced overall births to non-teens by about 2% and to teens by
      over 4%; estimates suggest a decline of 9% among newly eligible women. The
      reduction in fertility appears to have been accomplished via greater use of
      contraception. Our calculations indicate that allowing higher-income women to
      receive federally funded family planning cost on the order of $6,800 for each
      averted birth.

PMID- 20130788
TI  - Self-Assembled Collagen-like Peptide Fibers as Templates for Metallic Nanowires.
AB  - Inspired by nature's ability to fabricate supramolecular nanostructures from the
      bottom-up, materials scientist have become increasingly interested in the use of
      biomolecules like DNA, peptides, or proteins as templates for the creation of
      novel nanostructures and nanomaterials. Although the advantages of self
      assembling biomolecular structures clearly lie in their chemical diversity,
      spatial control, and numerous geometric architectures, it is challenging to
      elaborate them into functional hybrid inorganic-bionanomaterials without
      rendering the biomolecular scaffold damaged or dysfunctional. In this study,
      attachment of gold nanoparticles to collagen-related self-assembling peptides at
      L-lysine residues incorportated within the peptides sequence and the N-terminus
      led to metal nanoparticle-decorated fibers. After electroless silver plating,
      these fibers were completely metalized, creating electrically conductive
      nanowires under mild conditions while leaving the peptide fiber core intact. This
      study demonstrates the bottom-up assembly of synthetic peptidic fibers under mild
      conditions and their potential as templates for other complex inorganic-organic
      hybrid nanostructures.

PMID- 20130789
TI  - CE-MS analysis of the human urinary proteome for biomarker discovery and disease
      diagnostics.
AB  - Owing to its availability, ease of collection, and correlation with
      pathophysiology of diseases, urine is an attractive source for clinical
      proteomics. However, many proteomic studies have had only limited clinical
      impact, due to factors such as modest numbers of subjects, absence of disease
      controls, small numbers of defined biomarkers, and diversity of analytical
      platforms. Therefore, it is difficult to merge biomarkers from different studies
      into a broadly applicable human urinary proteome database. Ideally, the
      methodology for defining the biomarkers should combine a reasonable analysis time
      with high resolution, thereby enabling the profiling of adequate samples and
      recognition of sufficient features to yield robust diagnostic panels. Capillary
      electrophoresis coupled to mass spectrometry (CE-MS), which was used to analyze
      urine samples from healthy subjects and patients with various diseases, is a
      suitable approach for this task. The database of these datasets compiled from the
      urinary peptides enabled the diagnosis, classification, and monitoring of a wide
      range of diseases. CE-MS exhibits excellent performance for biomarker discovery
      and allows subsequent biomarker sequencing independent of the separation
      platform. This approach may elucidate the pathogenesis of many diseases, and
      better define especially renal and urological disorders at the molecular level.

PMID- 20130790
TI  - FMRI in translation: the challenges facing real-world applications.
AB  - Functional neuroimaging has increased our understanding of human brain function
      tremendously and has become a standard tool in clinical and cognitive
      neuroscience research. We briefly review its methodological foundations and
      describe remaining challenges for translational research. The application of
      neuroimaging results to individual subjects, for example in predicting treatment
      response or determining the veracity of a statement, is limited by these
      challenges, in particular by the anatomical and statistical procedures commonly
      employed. We thus argue for sincere caution in the translation of functional
      neuroimaging to real-world applications.

PMID- 20130791
TI  - The role of renal biopsy in a patient with multiple synchronous cancers: a case
      report.
AB  - A 51-year-old male with a long history of tobacco smoking presented to the
      outpatient clinic with left renal colic. A renal ultrasound revealed a mass in
      the left kidney. The patient was admitted to surgical clinic of Russian
      Scientific Center of Roentgen-Radiology of Rosmedtechnology. A renal biopsy and
      subsequent histopathological tests revealed adenocarcinoma of the right kidney of
      most likely metastatic origin. This discovery has lead to vigorous diagnostics
      search for the primary tumor. Finally, the following diagnosis was established:
      Primarily-multiple synchronous cancer: cancer of the left kidney T1N0M0, cancer
      of the thyroid gland T2N0M1, metastasis to the right kidney and lungs. The
      patient had left kidney and thyroid gland removed and was successfully treated
      with radioiodine therapy. The patient remains alive and well 7 months since his
      admission to our clinic. We report this case to emphasize the importance of the
      renal biopsy and thorough histological analysis, which made it possible to
      diagnose thyroid cancer in this patient.

PMID- 20130792
TI  - Tropomyosin period 3 is essential for enhancement of isometric tension in thin
      filament-reconstituted bovine myocardium.
AB  - Tropomyosin (Tm) consists of 7 quasiequivalent repeats known as "periods," and
      its specific function may be associated with these periods. To test the
      hypothesis that either period 2 or 3 promotes force generation by inducing a
      positive allosteric effect on actin, we reconstituted the thin filament with
      mutant Tm in which either period 2 (Delta2Tm) or period 3 (Delta3Tm) was deleted.
      We then studied: isometric tension, stiffness, 6 kinetic constants, and the pCa
      tension relationship. N-terminal acetylation of Tm did not cause any differences.
      The isometric tension in Delta2Tm remained unchanged, and was reduced to
      approximately 60% in Delta3Tm. Although the kinetic constants underwent small
      changes, the occupancy of strongly attached cross-bridges was not much different.
      The Hill factor (cooperativity) did not differ significantly between Delta2Tm
      (1.79 +/- 0.19) and the control (1.73 +/- 0.21), or Delta3Tm (1.35 +/- 0.22) and
      the control. In contrast, pCa(50) decreased slightly in Delta2Tm (5.11 +/- 0.07),
      and increased significantly in Delta3Tm (5.57 +/- 0.09) compared to the control
      (5.28 +/- 0.04). These results demonstrate that, when ions are present at
      physiological concentrations in the muscle fiber system, period 3 (but not period
      2) is essential for the positive allosteric effect that enhances the interaction
      between actin and myosin, and increases isometric force of each cross-bridge.

PMID- 20130793
TI  - Navigation by induction-based magnetoreception in elasmobranch fishes.
AB  - A quantitative frequency-domain model of induction-based magnetoreception is
      presented for elasmobranch fishes. We show that orientation with respect to the
      geomagnetic field can be determined by synchronous detection of electrosensory
      signals at harmonics of the vestibular frequency. The sensitivity required for
      this compass-sense mechanism is shown to be less than that known from behavioral
      experiments. Recent attached-magnet experiments have called into doubt the
      induction-based mechanism for magnetoreception. We show that the use of attached
      magnets would interfere with an induction-based mechanism unless relative
      movement between the electrosensory system and the attached magnet is less than
      100 mum. This suggests that further experiments may be required to eliminate
      induction as a basis for magnetoreception.

PMID- 20130794
TI  - Crystal Structural and Functional Analysis of the Putative Dipeptidase from
      Pyrococcus horikoshii OT3.
AB  - The crystal structure of a putative dipeptidase (Phdpd) from Pyrococcus
      horikoshii OT3 was solved using X-ray data at 2.4 A resolution. The protein is
      folded into two distinct entities. The N-terminal domain consists of the general
      topology of the alpha/beta fold, and the C-terminal domain consists of five long
      mixed strands, four helices, and two 3(10) helices. The structure of Phdpd is
      quite similar to reported structures of prolidases from P. furiosus (Zn-Pfprol)
      and P. horikoshii (Zn-Phdpd), where Zn ions are observed in the active site
      resulting in an inactive form. However, Phdpd did not contain metals in the
      crystal structure and showed prolidase activity in the absence of additional Co
      ions, whereas the specific activities increased by 5 times in the presence of a
      sufficient concentration (1.2 mM) of Co ions. The substrate specificities (X-Pro)
      of Phdpd were broad compared with those of Zn-Phdpd in the presence of Co ions,
      whose relative activities are 10% or less for substrates other than Met-Pro,
      which is the most favorable substrate. The binding constants of Zn-Phdpd with
      three metals (Zn, Co, and Mn) were higher than those of Phdpd and that with Zn
      was higher by greater than 2 orders, which were determined by DSC experiments.
      From the structural comparison of both forms and the above experimental results,
      it could be elucidated why the protein with Zn(2+) ions is inactive.

PMID- 20130795
TI  - Best of the 2008 sexual medicine society of north america: highlights from the
      sexual medicine society of north america, october 16-19, 2008, toronto, ontario,
      Canada.

PMID- 20130796
TI  - A New Journal Called LUTS: Lower Urinary Tract Symptoms.

PMID- 20130797
TI  - Chemical synthesis, characterization, and biocompatibility study of
      hydroxyapatite/chitosan phosphate nanocomposite for bone tissue engineering
      applications.
AB  - A novel bioanalogue hydroxyapatite (HAp)/chitosan phosphate (CSP) nanocomposite
      has been synthesized by a solution-based chemical methodology with varying HAp
      contents from 10 to 60% (w/w). The interfacial bonding interaction between HAp
      and CSP has been investigated through Fourier transform infrared absorption
      spectra (FTIR) and x-ray diffraction (XRD). The surface morphology of the
      composite and the homogeneous dispersion of nanoparticles in the polymer matrix
      have been investigated through scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM), respectively. The mechanical properties
      of the composite are found to be improved significantly with increase in
      nanoparticle contents. Cytotoxicity test using murine L929 fibroblast confirms
      that the nanocomposite is cytocompatible. Primary murine osteoblast cell culture
      study proves that the nanocomposite is osteocompatible and highly in vitro
      osteogenic. The use of CSP promotes the homogeneous distribution of particles in
      the polymer matrix through its pendant phosphate groups along with particle
      polymer interfacial interactions. The prepared HAp/CSP nanocomposite with uniform
      microstructure may be used in bone tissue engineering applications.

PMID- 20130798
TI  - Biologic agents-a panacea for inflammatory arthritis or not?
AB  - Aim. To describe the retention rates for biological therapies in patients with
      rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis
      (AS) in a clinical setting. Methods. All patients managed in a dedicated
      biological therapy clinic in a teaching hospital in Australia were assessed for
      continuation on biological treatments and reasons for switching to an alternative
      biological agent or cessation of treatment. Results. There was a lower retention
      rate for RA patients on biological therapies compared to PsA and AS patients and
      the retention rate for RA patients was lower than that reported in RCTs.
      Conclusions. The retention rate on biological therapies for RA patients was lower
      in the clinic setting than what is reported in RCTs. The reasons for the lower
      retention rate in the clinical setting are discussed but no clear determinants
      for nonresponse to biological agents were identifiable. These agents have very
      limited steroid sparing effects.

PMID- 20130799
TI  - Charge transport mechanism in thin cuticles holding nandi flame seeds.
AB  - Metal-sample-metal sandwich configuration has been used to investigate DC
      conductivity in 4 mum thick Nandi flame [Spathodea campanulata P. Beauv.] seed
      cuticles. J-V characteristics showed ohmic conduction at low fields and space
      charge limited current at high fields. Charge mobility in ohmic region was 4.06 x
      10(-5) (m(2)V(-1)s(-1)). Temperature-dependent conductivity measurements have
      been carried out in the temperature range 320 K < T > 450 K. Activation energy
      within a temperature of 320 K-440 K was about 0.86 eV. Variable range hopping
      (VRH) is the main current transport mechanism at the range of 330-440 K. The VRH
      mechanism was analyzed based on Mott theory and the Mott parameters: density of
      localized states near the Fermi-level N(E(F)) approximately 9.04 x 10(19) (eV(
      1)cm(-3)) and hopping distance R approximately 1.44 x 10(-7) cm, while the
      hopping energy (W) was in the range of 0.72 eV-0.98 eV.

PMID- 20130800
TI  - Reliability exercise for the polymyalgia rheumatica classification criteria
      study: the oranjewoud ultrasound substudy.
AB  - Objective. A study supported by the EULAR and the ACR being conducted to
      establish classification criteria for polymyalgia rheumatica (PMR) will include
      ultrasound examination of the shoulders and hips. Ultrasound (US) depicts
      glenohumeral joint effusion, biceps tenosynovitis, subdeltoid bursitis, hip joint
      synovitis, and trochanteric bursitis in PMR. These findings may aid in
      distinguishing PMR from other diseases. The purpose of this study was to assess
      standards and US interreader agreement of participants in the PMR classification
      criteria study. Methods. Sixteen physicians in four groups examined shoulders and
      hips of 4 patients and 4 healthy adults with ultrasound. Overall agreement and
      interobserver agreement were calculated. Results. The overall agreement (OA)
      between groups was 87%. The OA for healthy shoulders was 88.8%, for healthy hips
      100%, for shoulders with pathology 85.2%, and 74.3% for hips with pathology,
      respectively. Conclusion. There was a high degree of agreement found for the
      examination of healthy shoulders and pathologic hips. Agreement was moderate for
      pathologic shoulders and perfect for healthy hips. US of shoulder and hips
      performed by different examiners is a reliable and feasible tool for assessment
      of PMR related disease pathology and can be incorporated into a classification
      criteria study.

PMID- 20130801
TI  - Relationship between Investigative Biomarkers and Radiographic Grading in
      Patients with Knee Osteoarthritis.
AB  - Objective. To examine new investigative biomarkers and their relevance for
      radiographic severity in knee osteoarthritis. Methods. The group comprised 63
      patients with 73 knees examined. Patients were divided according to radiographic
      severity to allow for comparison of biomarker levels. Hyaluronic acid (HA),
      matrix metalloproteases (MMP-1, MMP-3 and MMP-13), tissue inhibitors of
      metalloproteases (TIMP-1 and TIMP-2), platelet-derived growth factor (PDGF-AB),
      transformed growth factor (TGF-beta), vascular endothelial growth factor (VEGF),
      hepatocyte growth factor (HGF) and insulin-like growth factor (IGF-I) were
      measured on synovial fluid and in plasma releasate at a single time point.
      Principal component analysis (PCA) followed by analysis of covariance were
      applied to evaluate data. Results. Four different groups of biomarker were
      identified in plasma releasates. The first (platelet number, PDGF-AB and TGF
      beta) and second groups (HA and IGF-I) were related to radiographic severity, P =
      .005 and P = .022, respectively. The third (MMP-1 and TIMP-2) and fourth groups
      (MMP-3 and TIMP-1) represented the catabolic balance, but were not associated to
      radiographic grading. Three different clusters of biomarkers were found in
      synovial fluid but did not show any significant association to radiographic
      grading. Conclusions. New imaging approaches to assess structural deterioration
      and correlation with biomarker levels are warranted to advance in OA research.

PMID- 20130802
TI  - Crystal structure studies of human dental apatite as a function of age.
AB  - Studies of the average crystal structure properties of human dental apatite as a
      function of age in the range of 5-87 years are reported. The crystallinity of the
      dental hydroxyapatite decreases with the age. The a-lattice constant that is
      associated with the carbonate content in carbonate apatite decreases with age in
      a systematic way, whereas the c-lattice constant does not change significantly.
      Thermogravimetric measurements demonstrate an increase of the carbonate content
      with the age. FTIR spectroscopy reveals both B and A-type carbonate substitutions
      with the B-type greater than the A-type substitution by a factor up to ~5. An
      increase of the carbonate content as a function of age can be deduced from the
      ratio of the nu(2)CO(3) to the nu(1)PO(4) IR modes.

PMID- 20130804
TI  - Adhesion of respiratory-infection-associated microorganisms on degradable
      thermoplastic composites.
AB  - The purpose of this study was to evaluate bacterial adhesion and early
      colonization on a composite consisting of bioactive glass (BAG) particles and
      copolymer of epsilon-caprolactone/D,L-lactide. Materials were incubated with
      suspensions of both type strains and clinical isolates of Streptococcus
      pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa for 30 minutes
      (adhesion) and 4 hours (colonization). Clear differences exist in the
      microorganisms' ability to adhere on the experimental materials. However, the
      presence of BAG particles does not inhibit bacterial adhesion, but early
      colonization of the materials with P. aeruginosa was inhibited by the addition of
      90-315 mum BAG particles.

PMID- 20130803
TI  - Baseline comorbidities in a population-based cohort of rheumatoid arthritis
      patients receiving biological therapy: data from the Australian rheumatology
      association database.
AB  - Aims. To describe the baseline characteristics of an Australian population-based
      cohort of rheumatoid arthritis (RA) patients commencing biological therapy.
      Methods. Descriptive analysis from the Australian Rheumatology Association
      Database (ARAD). Results. Up to October 2006, there were 681 RA patients taking
      biologics enrolled in ARAD. Baseline data were available for 624 (72% female,
      mean (SD) age 57.0 (12.5) years). Of these, 59.5% reported at least one comorbid
      condition, most commonly hypertension (35.7%) and osteoporosis (30.4%); 61 (9.8%)
      had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3
      melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina).
      Self-reported infections within the previous 6 months were common (71.5%).
      Conclusions. History of comorbidities, including recent infections, is common
      among Australian RA patients commencing biologics, and 10% have a history of
      malignancy. This may impact future evaluations of health outcomes among this
      population, including attribution of adverse events of biologic therapy.

PMID- 20130805
TI  - A biomimetic approach for the creation of two-dimensional microscale surface
      patterns: creation of isolated immunological synapses.
AB  - Current efforts in surface functionalization have not produced a robust technique
      capable of creating specific two-dimensional microscale geometrical arrays
      composed of multiple proteins. Such a capability is desirable for engineering
      substrates in sensing and cell patterning applications where at least two
      different protein functionalities in a specific configuration are required. Here
      we introduce a new approach for the creation of arrays of microscale geometries.
      We demonstrate our approach with a biomimetic structure inspired by the
      immunological synapse, a cell-cell interfacial structure characterized by two
      concentric rings of proteins: an outer adhesion protein structure and an inner
      recognition ligand core. The power of the technique lies in its ability to
      pattern any protein in any defined geometry as well as to create arrays in
      parallel.

PMID- 20130806
TI  - Molecular processes in biological thermosensation.
AB  - Since thermal gradients are almost everywhere, thermosensation could represent
      one of the oldest sensory transduction processes that evolved in organisms. There
      are many examples of temperature changes affecting the physiology of living
      cells. Almost all classes of biological macromolecules in a cell (nucleic acids,
      lipids, proteins) can present a target of the temperature-related stimuli. This
      review discusses some features of different classes of temperature-sensing
      molecules as well as molecular and biological processes that involve
      thermosensation. Biochemical, structural, and thermodynamic approaches are
      applied in the paper to organize the existing knowledge on molecular mechanisms
      of thermosensation. Special attention is paid to the fact that thermosensitive
      function cannot be assigned to any particular functional group or spatial
      structure but is rather of universal nature. For instance, the complex of
      thermodynamic, structural, and functional features of hemoglobin family proteins
      suggests their possible accessory role as "molecular thermometers".

PMID- 20130807
TI  - Accidental Removal of a Carotid Endovascular Stent during Oropharyngeal Mass
      Biopsy.
AB  - A 54-year-old male patient, with a history of a right mandibular adenocarcinoma,
      previously excised, and treated with post operative chemo- and radio-therapy,
      presented with a right oropharyngeal necrotic mass of several months duration.
      His history is pertinent for a right internal carotid endovascular stenting 2
      years prior to presentation. During biopsy of his oropharyngeal lesion, a
      specimen of tissue was retrieved, with the carotid stent within. There was no
      bleeding. To the best of our knowledge, there is no such case reported in the
      literature. We present this case as a reminder on the importance and risks of
      radiation-induced necrosis and its distortion of the surrounding anatomy,
      especially in the presence of foreign bodies or protheses.

PMID- 20130809
TI  - Roots of diversity relations.
AB  - The species-area relationship is one of the central generalizations in ecology;
      however, its origin has remained a puzzle. Since ecosystems are understood as
      energy transduction systems, the regularities in species richness are considered
      to result from ubiquitous imperatives in energy transduction. From a
      thermodynamic point of view, organisms are transduction mechanisms that
      distribute an influx of energy down along the steepest gradients to the
      ecosystem's diverse repositories of chemical energy, that is, populations of
      species. Transduction machineries, that is, ecosystems assembled from numerous
      species, may emerge and evolve toward high efficiency on large areas that hold
      more matter than small ones. This results in the well-known logistic-like
      relationship between the area and the number of species. The species-area
      relationship is understood, in terms of thermodynamics, to be the skewed
      cumulative curve of chemical energy distribution that is commonly known as the
      species-abundance relationship.

PMID- 20130808
TI  - Deoxycholate, an endogenous cytotoxin/genotoxin, induces the autophagic stress
      survival pathway: implications for colon carcinogenesis.
AB  - We report that deoxycholate (DOC), a hydrophobic bile acid associated with a high
      fat diet, activates the autophagic pathway in non-cancer colon epithelial cells
      (NCM-460), and that this activation contributes to cell survival. The DOC-induced
      increase in autophagy was documented by an increase in autophagic vacuoles
      (detected using transmission electron microscopy, increased levels of LC3-I and
      LC3-II (western blotting), an increase in acidic vesicles (fluorescence
      spectroscopy of monodansycadaverine and lysotracker red probes), and increased
      expression of the autophagic protein, beclin-1 (immunohistochemistry/western
      blotting). The DOC-induced increase in beclin-1 expression was ROS-dependent.
      Rapamycin (activator of autophagy) pre-treatment of NCM-460 cells significantly
      (P < .05) decreased, and 3-MA (inhibitor of autophagy) significantly (P < .05)
      increased the cell loss caused by DOC treatment, alone. Rapamycin pre-treatment
      of the apoptosis-resistant colon cancer cell line, HCT-116RC (developed in our
      laboratory), resulted in a significant decrease in DOC-induced cell death.
      Bafilomycin A(1) and hydroxychloroquine (inhibitors of the autophagic process)
      increased the DOC-induced percentage of apoptotic cells in HCT-116RC cells. It
      was concluded that the activation of autophagy by DOC has important implications
      for colon carcinogenesis and for the treatment of colon cancer in conjunction
      with commonly used chemotherapeutic agents.

PMID- 20130810
TI  - Exons 19 and 21 of epidermal growth factor receptor are highly conserved in
      squamous cell cancer of the head and neck.
AB  - Objective. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibition
      (TKI) is a promising treatment in upper aerodigestive malignancies. EGFR
      inhibitors might be more effective in patients whose tumors harbor specific EGFR
      mutations. The presence of specific EFGR mutations is predictive of over a 75%
      response rate to TKI therapies as compared to 10% in wild type cases of non-small
      cell lung cancer. Our objective was to examine whether these mutations might
      occur in upper aerodigestive cancers. Design. DNA was extracted from 20 head and
      neck squamous cell tumors and 4 squamous cell carcinoma cell lines and sequenced
      the receptor using published primer pairs. We then compared the results against
      published mutations. Results. No exon 19 or 21 mutations were found in any of the
      20 tumors and 0 of 4 cell lines. Based on the tumor data we would predict that no
      greater than 8% of head and neck tumors (CI 97.5%) would be likely to harbor
      either of these mutations. Conclusions. Our findings are comparable to results
      recently published of Korean, Austrian, and Spanish patient populations and we
      conclude that exon 19 and 21 EGFR mutations are not more common in head and neck
      cancer than in nonsmall-cell carcinoma.

PMID- 20130811
TI  - Donor complications following laparoscopic compared to hand-assisted living donor
      nephrectomy: an analysis of the literature.
AB  - THERE ARE TWO APPROACHES TO LAPAROSCOPIC DONOR NEPHRECTOMY: standard laparoscopic
      donor nephrectomy (LDN) and hand-assisted laparoscopic donor nephrectomy (HALDN).
      In this study we report the operative statistics and donor complications
      associated with LDN and HALDN from large-center peer-reviewed publications.
      Methods. We conducted PubMed and Ovid searches to identify LDN and HALDN outcome
      studies that were published after 2004. Results. There were 37 peer-reviewed
      studies, each with more than 150 patients. Cumulatively, over 9000 patients were
      included in this study. LDN donors experienced a higher rate of intraoperative
      complications than HALDN donors (5.2% versus. 2.0%, P < .001). Investigators did
      not report a significant difference in the rate of major postoperative
      complications between the two groups (LDN 0.5% versus HALDN 0.7%, P = .111).
      However, conversion to open procedures from vascular injury was reported more
      frequently in LDN procedures (0.8% versus 0.4%, P = .047). Conclusion. At present
      there is no evidence to support the use of one laparoscopic approach in
      preference to the other. There are trends in the data suggesting that
      intraoperative injuries are more common in LDN while minor postoperative
      complications are more common in HALDN.

PMID- 20130812
TI  - The influence of age and skull conductivity on surface and subdermal bipolar EEG
      leads.
AB  - Bioelectric source measurements are influenced by the measurement location as
      well as the conductive properties of the tissues. Volume conductor effects such
      as the poorly conducting bones or the moderately conducting skin are known to
      affect the measurement precision and accuracy of the surface
      electroencephalography (EEG) measurements. This paper investigates the influence
      of age via skull conductivity upon surface and subdermal bipolar EEG measurement
      sensitivity conducted on two realistic head models from the Visible Human
      Project. Subdermal electrodes (a.k.a. subcutaneous electrodes) are implanted on
      the skull beneath the skin, fat, and muscles. We studied the effect of age upon
      these two electrode types according to the scalp-to-skull conductivity ratios of
      5, 8, 15, and 30 : 1. The effects on the measurement sensitivity were studied by
      means of the half-sensitivity volume (HSV) and the region of interest sensitivity
      ratio (ROISR). The results indicate that the subdermal implantation notably
      enhances the precision and accuracy of EEG measurements by a factor of eight
      compared to the scalp surface measurements. In summary, the evidence indicates
      that both surface and subdermal EEG measurements benefit better recordings in
      terms of precision and accuracy on younger patients.

PMID- 20130813
TI  - Chronic Bilateral Slipped Capital Femoral Epiphysis as an Unusual Presentation of
      Congenital Panhypopituitarism due to Pituitary Hypoplasia in a 17-Year-Old
      Female.
AB  - We report an interesting case of a 17-year-old normal-statured female who was
      diagnosed with congenital panhypopituitarism due to pituitary hypoplasia at the
      presentation of bilateral slipped capital femoral epiphysis. We emphasized the
      importance of endocrinologic evaluation in patients with atypical slipped capital
      femoral epiphysis to prevent potential complication of adrenal crisis during
      surgery. This case also demonstrates growth without growth hormone which resulted
      in a delay in diagnosis of congenital hypopituitarism in this patient.

PMID- 20130814
TI  - Cell Cycle-Dependent Localization of Voltage-Dependent Calcium Channels and the
      Mitotic Apparatus in a Neuroendocrine Cell Line(AtT-20).
AB  - Changes in intracellular calcium are necessary for the successful progression of
      mitosis in many cells. Both elevation and reduction in intracellular calcium can
      disrupt mitosis by mechanisms that remain ill defined. In this study we explore
      the role of transmembrane voltage-gated calcium channels (CaV channels) as
      regulators of mitosis in the mouse corticotroph cell line (AtT-20). We report
      that the nifedipine-sensitive isoform CaV1.2 is localized to the "poleward side"
      of kinetechores during metaphase and at the midbody during cytokinesis. A second
      nifedipine-sensitive isoform, CaV1.3, is present at the mid-spindle zone in
      telophase, but is also seen at the midbody. Nifedipine reduces the rate of cell
      proliferation, and, utilizing time-lapse microscopy, we show that this is due to
      a block at the prometaphase stage of the cell cycle. Using Fluo-4 we detect
      calcium fluxes at sites corresponding to the mid-spindle zone and the midbody
      region. Another calcium dye, Fura PE3/AM, causes an inhibition of mitosis prior
      to anaphase that we attribute to a chelation of intracellular calcium. Our
      results demonstrate a novel, isoform-specific localization of CaV1 channels
      during cell division and suggest a possible role for these channels in the
      calcium-dependent events underlying mitotic progression in pituitary
      corticotrophs.

PMID- 20130815
TI  - Statistical analysis of variation in the human plasma proteome.
AB  - Quantifying the variation in the human plasma proteome is an essential
      prerequisite for disease-specific biomarker detection. We report here on the
      longitudinal and individual variation in human plasma characterized by two
      dimensional difference gel electrophoresis (2-D DIGE) using plasma samples from
      eleven healthy subjects collected three times over a two week period. Fixed
      effects modeling was used to remove dye and gel variability. Mixed-effects
      modeling was then used to quantitate the sources of proteomic variation. The
      subject-to-subject variation represented the largest variance component, while
      the time-within-subject variation was comparable to the experimental variation
      found in a previous technical variability study where one human plasma sample was
      processed eight times in parallel and each was then analyzed by 2-D DIGE in
      triplicate. Here, 21 protein spots had larger than 50% CV, suggesting that these
      proteins may not be appropriate as biomarkers and should be carefully scrutinized
      in future studies. Seventy-eight protein spots showing differential protein
      levels between different individuals or individual collections were identified by
      mass spectrometry and further characterized using hierarchical clustering. The
      results present a first step toward understanding the complexity of longitudinal
      and individual variation in the human plasma proteome, and provide a baseline for
      improved biomarker discovery.

PMID- 20130816
TI  - Kinetics and determining factors of the virologic response to antiretrovirals
      during pregnancy.
AB  - HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at
      delivery pose a minimal risk of vertical transmission. We studied the kinetics
      and the determinants of the virologic response to antiretroviral therapy in 117
      consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL
      decrease of 2 and 2.5 log(10) after 4 and 24 weeks, respectively. Therapeutic
      drug monitoring (TDM) of the protease inhibitors administered in doses
      recommended for nonpregnant adults resulted in below-target concentrations in
      29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but
      low drug concentrations did not correlate with virologic failure. Demographic
      characteristics, antiretroviral experience prior to pregnancy, baseline VL, or
      use of specific antiretrovirals did not affect the virologic response. Adherence
      to >/=95% of prescribed doses and utilization of psychosocial services were
      associated with undetectable plasma HIV RNA at delivery. In conclusion, the
      virologic responses of pregnant and nonpregnant adults share similar
      characteristics.

PMID- 20130817
TI  - Genotypic and Phenotypic Assessment of Hyaluronidase among Type Strains of a
      Select Group of Staphylococcal Species.
AB  - Hyaluronidases degrade hyaluronic acid, a major polysaccharide of the
      extracellular matrix of tissues, and are considered important for virulence in a
      number of Gram-positive and -negative bacteria. The purpose of the present study
      was to determine the prevalence of hyaluronidase among clinical strains of
      Staphylococcus aureus and among other Staphylococcus species. Spent media and
      chromosomal DNA were assessed for hyaluronidase activity and the absence or
      presence of a hyaluronidase gene (hysA) by Southern analysis, respectively. All
      S. aureus strains examined exhibited at least one hybridizing band (half of the
      strains exhibited two or more hybridizing bands) when probed for hysA and all but
      three of these strains produced hyaluronidase. In contrast, none of the type
      strains of 19 other species exhibited either hyaluronidase activity or
      hybridizing bands when probed for hysA. These data support the hypothesis that
      among members of the Staphylococcus genus only strains of S. aureus possess the
      enzyme hyaluronidase. This would suggest that hyaluronidase represents yet
      another potential virulence factor employed by S. aureus to cause disease and may
      represent a diagnostically important characteristic for distinguishing S. aureus
      from other members of this genus.

PMID- 20130818
TI  - Targeted therapy in ovarian cancer.
AB  - Ovarian cancer is the most common cause of mortality of tumors from gynecologic
      origin and is often diagnosed after patients have already progressed to advanced
      disease stage. The current standard of care for treatment of ovarian cancer
      includes cytoreductive surgery followed by adjuvant chemotherapy. Unfortunately,
      many patients will recur and ultimately die from their disease. Targeted
      therapies have been evaluated in ovarian cancer as a method to overcome resistant
      disease. Angiogenesis inhibitors have shown success in many tumor types and have
      also demonstrated promise in trials involving patients with ovarian cancer. PARP
      inhibitors may be potentially active agents in patients with BRCA-associated
      ovarian cancer. Trials that have evaluated combinations of targeted agents have
      often revealed untoward toxicities, thus tempering enthusiasm for this approach.

PMID- 20130819
TI  - Cold exposure exacerbates the development of diabetic polyneuropathy in the rat.
AB  - Diabetic polyneuropathy (DPN) and cold-induced nerve injury share several
      pathogenic mechanisms. This study explores whether cold exposure contributes to
      the development of DPN. Streptozotocin-induced diabetic rats and controls were
      exposed to a room temperature (23 degrees C) or cold environment (10 degrees C).
      H-reflex, tail and sciatic motor, and sensory nerve conduction studies were
      performed. Analyses of sural nerve, intraepidermal nerve fibers, and skin and
      nerve nitrotyrosine ELISAs were performed. Diabetic animals exposed to a cold
      environment had an increased H-reflex four weeks earlier than diabetic room
      temperature animals (P = .03). Cold-exposed diabetic animals also had greater
      reduction in motor conduction velocities at 20 weeks (P = .017), decreased skin
      nerve fiber density (P = .037), and increased skin nitrotyrosine levels (P =
      .047). Cold exposure appears to hasten the development of DPN in the rat STZ
      model of diabetes. These findings support that further study into the
      relationship between ambient temperature and DPN is warranted.

PMID- 20130820
TI  - Combined use of MS2 and PP7 coat fusions shows that TIA-1 dominates hnRNP A1 for
      K-SAM exon splicing control.
AB  - Splicing of the FGFR2 K-SAM exon is repressed by hnRNP A1 bound to the exon and
      activated by TIA-1 bound to the downstream intron. Both proteins are expressed
      similarly by cells whether they splice the exon or not, so it is important to
      know which one is dominant. To answer this question, we used bacteriophage PP7
      and bacteriophage MS2 coat fusions to tether hnRNP A1 and TIA-1 to distinct sites
      on the same pre-mRNA molecule. hnRNP A1 fused to one coat protein was tethered to
      a K-SAM exon containing the corresponding coat protein's binding site. TIA-1
      fused to the other coat protein was tethered to the downstream intron containing
      that coat protein's binding site. This led to efficient K-SAM exon splicing. Our
      results show that TIA-1 is dominant for K-SAM exon splicing control and validate
      the combined use of PP7 and MS2 coat proteins for studying posttranscriptional
      events.

PMID- 20130821
TI  - Role of BMP-4 and Its Signaling Pathways in Cultured Human Melanocytes.
AB  - Bone Morphogenetic Protein (BMP-4) was shown to down-regulate melanogenesis, in
      part, by decreasing the level of tyrosinase [Yaar et al. (2006) JBC:281]. Results
      presented here show that BMP-4 down-regulated the protein levels of TRP-1, PKC
      beta, and MCI-R. When paired cultures of human melanocytes were treated with
      vehicle or BMP-4 (25 ng/ml), MAPK/ERK were phosphorylated within one hour of BMP
      4 treatment. Then the activated MAPK/ERK caused an acute phosphorylation of MITF,
      followed by proteosome-mediated degradation of MITF, the key transcription factor
      for melanogenic proteins [Wu et al. (2000) Gene & Development:14]. However,
      prolonged exposure of melanocytes to BMP-4 (up to 48 hours) caused a decrease in
      the level of MITF-M transcript. In addition, BMP-4 decreased the intracellular
      level of cAMP, the key regulator of MITF expression. These results demonstrate
      that BMP-4 activates MAPK/ERK signaling pathway to transiently activate MITF;
      however, chronic treatment of BMP-4 to melanocytes causes a down-regulation of
      the expression of MITF, possibly in a cAMP-dependent pathway.

PMID- 20130822
TI  - Parasitic diseases, diagnostic approaches, and therapies.

PMID- 20130823
TI  - Serum profiles of C-reactive protein, interleukin-8, and tumor necrosis factor
      alpha in patients with acute pancreatitis.
AB  - BACKGROUND/AIMS: Early prediction of the severity of acute pancreatitis would
      lead to prompt intensive treatment resulting in improvement of the outcome. The
      present study investigated the use of C-reactive protein (CRP), interleukin IL-8
      and tumor necrosis factor-alpha (TNF-alpha) as prognosticators of the severity of
      the disease. METHODS: Twenty-six patients with acute pancreatitis were studied.
      Patients with APACHE II score of 9 or more formed the severe group, while the
      mild group consisted of patients with APACHE II score of less than 9. Serum
      samples for measurement of CRP, IL-8 and TNF-alpha were collected on the day of
      admission and additionally on the 2nd, 3rd and 7th days. RESULTS: Significantly
      higher levels of IL-8 were found in patients with severe acute pancreatitis
      compared to those with mild disease especially at the 2nd and 3rd days (P = .001
      and P = .014, resp.). No significant difference for CRP and TNF-alpha was
      observed between the two groups. The optimal cut-offs for IL-8 in order to
      discriminate severe from mild disease at the 2nd and 3rd days were 25.4 pg/mL and
      14.5 pg/mL, respectively. CONCLUSIONS: IL-8 in early phase of acute pancreatitis
      is superior marker compared to CRP and TNF-alpha for distinguishing patients with
      severe disease.

PMID- 20130824
TI  - Anti-EphA2 Antibodies with Distinct In Vitro Properties Have Equal In Vivo
      Efficacy in Pancreatic Cancer.
AB  - The EphA2 receptor tyrosine kinase is overexpressed in a variety of human
      epithelial cancers and is a determinant of malignant cellular behavior in
      pancreatic adenocarcinoma cells. Moreover, it is expressed in tumor endothelium
      and its activation promotes angiogenesis. To better clarify the therapeutic
      potential of monoclonal antibodies (mAbs) directed to the EphA2 receptor, we
      generated a large number of mAbs by differential screening of phage-Ab libraries
      by oligonucleotide microarray technology and implemented a strategy for the rapid
      identification of antibodies with the desired properties. We selected two high
      affinity and highly specific EphA2 monoclonal antibodies with different in vitro
      properties on the human pancreatic tumor cell line MiaPaCa2. One is a potent
      EphA2-agonistic antibody, IgG25, that promotes receptor endocytosis and
      subsequent degradation, and the second is a ligand antagonist, IgG28, that blocks
      the binding to ephrin A1 and is cross-reactive with the mouse EphA2 receptor. We
      measured the effect of antibody treatment on the growth of MiaPaCa2 cells
      orthotopically transplanted in nude mice. Both IgG25 and IgG28 had strong
      antitumor and antimetastatic efficacy. In vivo treatment with IgG25 determined
      the reduction of the EphA2 protein levels in the tumor and the phosphorylation of
      FAK on Tyr576 while administration of IgG28 caused a decrease in tumor
      vascularization as measured by immunohistochemical analysis of CD31 in tumor
      sections. These data show that in a pancreatic cancer model comparable
      therapeutic efficacy is obtained either by promoting receptor degradation or by
      blocking receptor activation.

PMID- 20130826
TI  - Involvement of SOX10 in the pathogenesis of Hirschsprung disease: report of a
      truncating mutation in an isolated patient.
AB  - SOX10 protein is a key transcription factor during neural crest development.
      Mutations in SOX10 are associated with several neurocristopathies such as
      Waardenburg syndrome type IV (WS4), a congenital disorder characterized by the
      association of hearing loss, pigmentary abnormalities, and absence of ganglion
      cells in the myenteric and submucosal plexus of the gastrointestinal tract, also
      known as aganglionic megacolon or Hirschsprung disease (HSCR). Several mutations
      at this locus are known to cause a high percentage of WS4 cases, but no SOX10
      mutations had been ever reported associated to isolated HSCR patient. Therefore,
      nonsyndromic HSCR was initially thought not to be associated to mutations at this
      particular locus. In the present study, we describe the evaluation of the SOX10
      gene in a series of 196 isolated HSCR cases, the largest patient series evaluated
      so far, and report a truncating c.153-155del mutation. This is the first time
      that a SOX10 mutation is detected in an isolated HSCR patient, which completely
      changes the scenario for the implications of SOX10 mutations in human disease,
      giving us a new tool for genetic counseling.

PMID- 20130827
TI  - New postcrania of Deccanolestes from the Late Cretaceous of India and their
      bearing on the evolutionary and biogeographic history of euarchontan mammals.
AB  - Extant species of the supraordinal mammal clade Euarchonta belong to the orders
      Primates, Scandentia, or Dermoptera. The fossil record of euarchontans suggests
      that they underwent their initial radiation during the Paleocene (65-55 million
      years ago) in North America, Eurasia, and Africa. The time and place of origin is
      poorly resolved due to lack of definitive fossils of euarchontan stem taxa. We
      describe a fragmentary humerus and two fragmentary ulnae from the latest
      Cretaceous of India that bear significantly on this issue. The fossils are
      tentatively referred to Deccanolestes cf. hislopi due to their small size and the
      fact that Deccanolestes is the only eutherian dental taxon to have been recovered
      from the same locality. The new fossils are used to evaluate the existing
      behavioral hypothesis that Deccanolestes was arboreal, and the competing
      phylogenetic hypotheses that Deccanolestes is a stem eutherian versus a stem
      euarchontan. The humerus resembles those of euarchontans in possessing a
      laterally keeled ulnar trochlea, a distinct zona conoidea, and a spherical
      capitulum. These features also suggest an arboreal lifestyle. The ulnar
      morphology is consistent with that of the humerus in reflecting an
      arboreal/scansorial animal. Detailed quantitative comparisons indicate that,
      despite morphological correlates to euarchontan-like arboreality, the humerus of
      Deccanolestes is morphologically intermediate between those of Cretaceous
      "condylarthran" mammals and definitive Cenozoic euarchontans. Additionally,
      humeri attributed to adapisoriculids are morphologically intermediate between
      those of Deccanolestes and definitive euarchontans. If adapisoriculids are
      euarchontans, as recently proposed, our results suggest that Deccanolestes is
      more basal. The tentative identification of Deccanolestes as a basal stem
      euarchontan suggests that (1) Placentalia began to diversify and Euarchonta
      originated before the Cretaceous-Tertiary boundary and (2) the Indian
      subcontinent, Eurasia, and Africa are more likely places of origin for Euarchonta
      than is North America.

PMID- 20130828
TI  - The interrater reliability of SAPS II and SAPS 3.
AB  - PURPOSE: In this study we evaluated and compared the interrater reliability of
      SAPS II and SAPS 3 in order to measure the consistency of performance among
      different raters. METHOD: Ten junior doctors working at two general ICUs were
      trained in the use of SAPS II and SAPS 3 using a 2.5-h training program. After
      training they scored 24 cases in both systems. Scores were analyzed using
      intraclass correlation coefficient (ICC) statistics. In order to identify
      variables with low reliability, subscores were analyzed using the ICC, and single
      variables were compared to a template score using weighted kappa statistics.
      RESULTS: The ICC (95% CI) of the scores was 0.84 (0.74, 0.91) in SAPS II and 0.80
      (0.68, 0.89) in SAPS 3, which is considered adequate for both systems. Mean
      mortality predictions among the raters had a range of 0.12 in SAPS II and 0.19 in
      SAPS 3. Administrative data including age had high reliability, whereas variables
      based on diagnostic information had only moderate reliability. Laboratory data
      had consistently higher reliability than variables based on the interpretation of
      charts. CONCLUSION: Both SAPS II and SAPS 3 have adequate interrater reliability,
      but the standardized mortality ratios are still likely to be influenced by the
      rater's scoring practice.

PMID- 20130829
TI  - Sildenafil for pulmonary hypertension in ARDS: a new pleasant effect?

PMID- 20130830
TI  - Sildenafil attenuates pulmonary arterial pressure but does not improve
      oxygenation during ARDS.
AB  - OBJECTIVE: Pulmonary hypertension is a characteristic feature of acute
      respiratory distress syndrome (ARDS) and contributes to mortality. Administration
      of sildenafil in ambulatory patients with pulmonary hypertension improves
      oxygenation and ameliorates pulmonary hypertension. Our aim was to determine
      whether sildenafil is beneficial for patients with ARDS. DESIGN: Prospective,
      open-label, multicenter, interventional cohort study. SETTING: Medical-surgical
      ICU of two university hospitals. PATIENTS: Ten consecutive patients meeting the
      NAECC criteria for ARDS. INTERVENTIONS: A single dose of 50 mg sildenafil citrate
      administered via a nasogastric tube. MAIN RESULTS: Administration of sildenafil
      in patients with ARDS decreased mean pulmonary arterial pressure from 25 to 22
      mmHg (P = 0.022) and pulmonary artery occlusion pressure from 16 to 13 mmHg (P =
      0.049). Systemic mean arterial pressures were markedly decreased from 81 to 75
      mmHg (P = 0.005). Sildenafil did not improve pulmonary arterial oxygen tension,
      but resulted in a further increase in the shunt fraction. CONCLUSION: Although
      sildenafil reduced pulmonary arterial pressures during ARDS, the increased shunt
      fraction and decreased arterial oxygenation render it unsuitable for the
      treatment of patients with ARDS.

PMID- 20130831
TI  - Prone positioning for ARDS: defining the target.

PMID- 20130832
TI  - Prone ventilation reduces mortality in patients with acute respiratory failure
      and severe hypoxemia: systematic review and meta-analysis.
AB  - BACKGROUND: Prone position ventilation for acute hypoxemic respiratory failure
      (AHRF) improves oxygenation but not survival, except possibly when AHRF is
      severe. OBJECTIVE: To determine effects of prone versus supine ventilation in
      AHRF and severe hypoxemia [partial pressure of arterial oxygen (PaO(2))/inspired
      fraction of oxygen (FiO(2)) <100 mmHg] compared with moderate hypoxemia (100 mmHg
      < or = PaO(2)/FiO(2) < or = 300 mmHg). DESIGN: Systematic review and meta
      analysis. DATA SOURCES: Electronic databases (to November 2009) and conference
      proceedings. METHODS: Two authors independently selected and extracted data from
      parallel-group randomized controlled trials comparing prone with supine
      ventilation in mechanically ventilated adults or children with AHRF. Trialists
      provided subgroup data. The primary outcome was hospital mortality in patients
      with AHRF and PaO(2)/FiO(2) <100 mmHg. Meta-analyses used study-level random
      effects models. RESULTS: Ten trials (N = 1,867 patients) met inclusion criteria;
      most patients had acute lung injury. Methodological quality was relatively high.
      Prone ventilation reduced mortality in patients with PaO(2)/FiO(2) <100 mmHg
      [risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74-0.96; p = 0.01; seven
      trials, N = 555] but not in patients with PaO(2)/FiO(2) > or =100 mmHg (RR 1.07,
      95% CI 0.93-1.22; p = 0.36; seven trials, N = 1,169). Risk ratios differed
      significantly between subgroups (interaction p = 0.012). Post hoc analysis
      demonstrated statistically significant improved mortality in the more hypoxemic
      subgroup and significant differences between subgroups using a range of
      PaO(2)/FiO(2) thresholds up to approximately 140 mmHg. Prone ventilation improved
      oxygenation by 27-39% over the first 3 days of therapy but increased the risks of
      pressure ulcers (RR 1.29, 95% CI 1.16-1.44), endotracheal tube obstruction (RR
      1.58, 95% CI 1.24-2.01), and chest tube dislodgement (RR 3.14, 95% CI 1.02-9.69).
      There was no statistical between-trial heterogeneity for most clinical outcomes.
      CONCLUSIONS: Prone ventilation reduces mortality in patients with severe
      hypoxemia. Given associated risks, this approach should not be routine in all
      patients with AHRF, but may be considered for severely hypoxemic patients.

PMID- 20130834
TI  - Radiographic guided drilling of bony tibial tunnels for fixation of meniscus
      transplants using percentage references.
AB  - The objective of our investigation was to evaluate the precision of radiographic
      guided tibial tunnel drilling for anatomical anchoring of meniscus transplants at
      the tibial insertion areas. In 20 cadaveric proximal tibiae, the meniscal
      insertions were dissected and their circumferences outlined. Standardized
      photographs of the tibial plateau were obtained. Applying established percentage
      values for radiographic determination of the meniscus insertion midpoints, tibial
      tunnels were drilled using a standard ACL-guide. Guide positioning was performed
      by using the midpoints as determined on standard AP and lateral radiographs.
      After tibial tunnel drilling, a second set of standardized photographs of the
      tibial plateau was obtained. Digital imaging permitted the superposition of pre-
      and postoperative images. Overlapping between the anatomical insertion areas and
      the tibial tunnel exit was determined, as well as the distance between the
      borders of the insertion areas and the tunnel exit. Insertion area and tunnel
      exit showed a mean overlapping of 59.8 +/- 34.8% (anterior horn), respectively
      62.4 +/- 32.0% (posterior horn) for the lateral meniscus and of 88.4 +/- 15.5%
      (anterior horn), respectively 60.3 +/- 31.6% (posterior horn) for the medial
      meniscus. Mean distance between the borders of insertion area and tunnel exit was
      2.0 +/- 1.5 mm (anterior horn), respectively 2.0 +/- 1.7 mm (posterior horn) for
      the lateral meniscus and 0.9 +/- 0.9 mm (anterior horn), respectively 2.1 +/- 1.4
      mm (posterior horn) for the medial meniscus. Thus, a precise drilling of tibial
      tunnels at the anatomical insertions of the menisci can be obtained by
      positioning a standard ACL-guide under radiographic control in a cadaver setting.
      In advanced day-by-day clinic, this knowledge could facilitate the surgical
      technique for anatomical fixation of lateral and medial meniscus transplants.

PMID- 20130833
TI  - The subchondral bone in articular cartilage repair: current problems in the
      surgical management.
AB  - As the understanding of interactions between articular cartilage and subchondral
      bone continues to evolve, increased attention is being directed at treatment
      options for the entire osteochondral unit, rather than focusing on the articular
      surface only. It is becoming apparent that without support from an intact
      subchondral bed, any treatment of the surface chondral lesion is likely to fail.
      This article reviews issues affecting the entire osteochondral unit, such as
      subchondral changes after marrow-stimulation techniques and meniscectomy or large
      osteochondral defects created by prosthetic resurfacing techniques. Also
      discussed are surgical techniques designed to address these issues, including the
      use of osteochondral allografts, autologous bone grafting, next generation cell
      based implants, as well as strategies after failed subchondral repair and
      problems specific to the ankle joint. Lastly, since this area remains in constant
      evolution, the requirements for prospective studies needed to evaluate these
      emerging technologies will be reviewed.

PMID- 20130835
TI  - Sagittal flexion angle of the femoral component in unicompartmental knee
      arthroplasty: is it same for both medial and lateral UKAs?
AB  - The flexion of the femoral component in the sagittal plane in unicompartmental
      knee arthroplasty (UKA) was analyzed radiographically in this study. Thirty
      medial and 30 lateral UKAs were included. The sagittal flexion angles were
      measured both relative to the posterior femoral cortex and midline sagittal
      distal femoral axis. Both of the measurement methods revealed that the femoral
      components were inserted in a significantly more flexed fashion in the medial UKA
      group. Neither preoperative nor postoperative tibial slope did have any
      significant effect on the sagittal flexion angle. To the best of our knowledge,
      this is the first study demonstrating an angular difference in the sagittal
      flexion of the femoral components between medial and lateral UKAs.

PMID- 20130836
TI  - A comparison of intraarticular morphine and bupivacaine for pain control and
      outpatient status after an arthroscopic knee surgery under a low dose of spinal
      anaesthesia.
AB  - Effective pain control is important after an outpatient arthroscopic knee surgery
      to permit early discharge and improve outcome. The aim of this study was to
      compare intraarticular morphine and bupivacaine with placebo for postoperative
      pain control and outpatient status after a knee arthroscopic surgery under a low
      dose of spinal anaesthesia. After obtaining the ethic committee's approval and
      written informed consents from 60 adult outpatients undergoing knee arthroscopy,
      patients were enrolled in this prospective, randomized, double-blinded, placebo
      controlled clinical study. All patients received spinal anaesthesia with 1.4 ml
      of hyperbaric bupivacaine 0.5%. Patients were randomly divided into three groups
      as morphine (group M, n =20), bupivacaine (group B, n = 20), and placebo (group
      C, n = 20). After the surgical procedure, patients received one of the following
      solutions intraarticularly in a double-blinded randomized manner: 5 mg morphine
      in 20 ml saline, 20 ml 0.25% bupivacaine, or 20 ml saline. Postoperative pain was
      assessed using a 10-cm visual analogue scale (VAS). Patient characteristics,
      hemodynamic values, sensory and motor blocks, VAS values, rescue analgesics,
      discharge time, and patient satisfaction were recorded. There were no significant
      differences in patient characteristics, surgery and tourniquet time, hemodynamic
      values, and sensory and motor blocks. The VAS values at 30, 60, and 90 min were
      similar among the three groups. The VAS values at rest and during move were
      higher in group C than in groups M and B at 120, 150, 180 min, and 24 h (P <
      0.001). There was no difference in VAS values between the groups M and B. Rescue
      analgesics used and discharge time were significantly different in the placebo
      group when compared to groups M and B (P < 0.001). Side effects were similar
      among the groups. Patient satisfaction scores were high in the groups M and B.
      Administration of 5 mg morphine and 20 ml of 0.25% bupivacaine intraarticularly
      provides better pain relief and shorter discharge time without increasing the
      side effects than placebo for an outpatient arthroscopic knee surgery performed
      under a low dose of spinal anaesthesia.

PMID- 20130837
TI  - Transphyseal reconstruction of the anterior cruciate ligament in prepubescent
      athletes.
AB  - ACL reconstruction in adolescents undergoing or being beyond the final growth
      spurt can be performed as in adults without major concern of growth disturbance.
      Whereas for the young athlete with wide-open physis a lot of controversy still
      exists about the technical aspect of the procedure to minimise the risk of growth
      disturbance. Between 10/1997 and 10/2002 31 children graded Tanner stage 1 or 2
      (median age 11 years) with an intraligamental rupture of the anterior cruciate
      ligament were enrolled. Seventeen patients with coexisting intraarticular damage
      (meniscus, osteochondral flake) underwent transphsyeal reconstruction of the ACL
      with the use of an autogenous semitendinosus tendon graft, whereas 14 patients
      without coexisting pathologies received a nonoperative regime. Growth
      disturbance, functional and radiographic outcome could be evaluated in 28
      patients at a median of 70 months after initial treatment. No patient had
      clinical or radiological evidence for varus/valgus malalignment or leg length
      discrepancy. The mean of subsequent body growth within the study population was
      20.3 cm. Patients operated on revealed significant (P < 0.05) better clinical (KT
      1000 side-to-side difference, pivot shift) and functional results according to
      the IKDC (median, 95 vs. 87), Lysholm (median, 93 vs. 84) and the Tegner score.
      More than half of the conservatively treated patients (58%) had subsequent
      surgery due to persistent instability. Transphyseal reconstruction of
      intraligamental ACL ruptures with an autologous ST graft yielded superior
      clinical results if compared to a nonoperative treatment in immature prepubescent
      patients being Tanner stage 1 and 2.

PMID- 20130839
TI  - The femoral sulcus in total knee arthroplasty.

PMID- 20130840
TI  - Microfracture for chondral defects of the talus: maintenance of early results at
      midterm follow-up.
AB  - We determined whether the early improvement in symptoms and function after
      microfracture in the management of articular cartilage defects of the talus is
      maintained at mid term follow-up. Factors influencing outcome and postoperative
      magnetic resonance imaging were also evaluated. We performed data collection
      prospectively using the Hannover Scoring System for the ankle (HSS) and a Visual
      Analog Scale (VAS) for pain and function preoperatively, at 1 +/- 0.1 year (45
      ankles), 2 +/- 0.4 years (45 ankles), and at an average of 5.8 +/- 2.0 years (39
      ankles) postoperatively. MRI was used to assess cartilage repair tissue based on
      the following variables: degree of defect repair and filling of the defect,
      integration to border zone, surface of the repair tissue, structure of the repair
      tissue and subchondral bone alterations. Comparing the outcome scores of the last
      follow-up to the previous follow-up points, the HSS and the VAS (pain, function
      and satisfaction) showed no deterioration. Four ankles, however, underwent
      further surgery to address the chondral defect and were regarded as failures. A
      body mass index greater than 25 kg/m(2) and having severe post-traumatic
      cartilage damage appeared to be negative prognostic factors. Results for patients
      older than 50 years were not inferior to those in younger patients. Microfracture
      arthroplasty induces repair of localized articular cartilage defects of the talus
      maintaining the encouraging early results at mid term follow-up.

PMID- 20130841
TI  - Baseline atherosclerosis parameter could assess the risk of bone loss during
      pioglitazone treatment in type 2 diabetes mellitus.
AB  - SUMMARY: We found that serum osteocalcin, femoral bone mineral density (F-BMD),
      and 1/3R-BMD were decreased during pioglitazone treatment in patients with type 2
      diabetes. Moreover, baseline atherosclerosis parameter, serum insulin-like growth
      factor-I (IGF-I), and urinary N-terminal cross-linked telopeptide of type I
      collagen (uNTX) values were associated with changes in bone mineral density
      (BMD). Therefore, these parameters could assess the risk of BMD reduction in
      patients treated with pioglitazone. INTRODUCTION: The aim of this study was to
      investigate the effects of pioglitazone or metformin on bone mass and
      atherosclerosis in patients with type 2 diabetes. METHODS: A total of 55 Japanese
      patients were enrolled in this 1-year open-label study and randomized to either
      pioglitazone (n = 22, 15-30 mg/day) or metformin (n = 23, 500-750 mg/day) groups.
      BMD at the lumbar spine, femoral neck (F), and one third of the radius (1/3R),
      bone markers, and atherosclerosis parameters were measured. RESULTS: In the
      pioglitazone group, serum osteocalcin significantly decreased at 6 months (p <
      0.05), although it almost recovered to baseline level at 12 months. F-BMD
      significantly decreased at 6 months (p < 0.05), and 1/3R-BMD significantly
      decreased at 6 and 12 months (p < 0.05), while bone markers or BMD at any site
      were not changed in the metformin group. Although atherosclerosis parameters were
      not changed in the pioglitazone group, intima-media thickness (IMT)-mean
      significantly increased at 6 months (p < 0.05) and plaque score significantly
      increased at 6 and 12 months (p < 0.01) in the metformin group. In the
      pioglitazone group, %changes in F-BMD were significantly and negatively
      correlated with baseline IMT-Max, IMT-mean, and plaque scores (r = -0.61, p <
      0.01; r = -0.71, p < 0.01; and r = -0.68, p < 0.01, respectively), and %changes
      in 1/3R-BMD were significantly and negatively correlated with baseline uNTX and
      IMT-Max (r = -0.57, p < 0.01 and r = -0.48, p < 0.05, respectively) and
      positively with IGF-I (r = 0.45, p < 0.05). CONCLUSIONS: Baseline IMT, uNTX, and
      IGF-I could assess the risk of BMD reduction in diabetic patients treated with
      pioglitazone.

PMID- 20130842
TI  - Age-related changes in hepatic expression and activity of cytochrome P450 in male
      rats.
AB  - Age-related changes in hepatic expression and activity of cytochrome P450 (CYP)
      were investigated in male rats aged 3 (weanling), 12 (young), 26 (adult), and 104
      (old) weeks. Levels of microsomal protein, total CYP, and cytochrome b(5)
      increased fully after puberty. CYP1A1 was detected only in 3-week-old rats, and
      CYP1A2, CYP2B1, and CYP2E1 were maximally expressed at 3 weeks but decreased at
      12 and 26 weeks. CYP2C11 and CYP3A2 increased markedly after puberty and
      decreased with aging. Ethoxyresorufin-O-deethylase, methoxyresorufin-O
      demethylase, pentoxyresorufin-O-depenthylase, and p-nitrophenol hydroxylase
      activities were at their highest in 3-week-old rats, and midazolam hydroxylase
      activity was at a maximum in 12-week-old rats but decreased with aging. The
      present results show that increasing age caused significant alterations in
      hepatic expression/activity of CYP isoforms in an isoform-specific manner. These
      results suggest that age-related changes in hepatic CYP isoforms may be an
      important factor for deciding the efficacy and safety of xenobiotics.

PMID- 20130843
TI  - Atomic layer deposition (ALD) as a coating tool for reinforcing fibers.
AB  - Layers of alumina were deposited on to bundled carbon fibers in an atomic layer
      deposition (ALD) process via sequential exposure to vapors of aluminium chloride
      and water, respectively. Scanning electron microscopic (SEM) images of the coated
      fibers revealed that each individual fiber within a bundle was coated evenly and
      separately, fibers are not bridged by the coating. SEM and transmission electron
      microscopic (TEM) images indicate that the coating was uniform and conformal with
      good adhesion to the fiber surface. Average deposition rate, measured from SEM
      images, was 0.06 nm per cycle at 500  degrees C. SEM also revealed that at
      deposition temperatures of 500  degrees C few of the fibers were damaged. At
      temperatures of 300  degrees C, no damaged fibers were observed, the average
      deposition rate decreased down to 0.033 nm per cycle. Oxidation resistance of the
      alumina-coated fibers was characterized by thermogravimetric analysis (TGA). The
      alumina coating improved oxidation resistance of the carbon fiber significantly.
      Oxidation onset temperature was 600  degrees C for fibers coated with a 45 nm
      thick alumina. Uncoated fibers, on the other hand, started to oxidize at
      temperatures as low as 250  degrees C.

PMID- 20130844
TI  - A fully validated high-performance liquid chromatography-tandem mass spectrometry
      method for the determination of ethyl glucuronide in hair for the proof of strict
      alcohol abstinence.
AB  - Hair analysis has become a powerful tool for the detection of chronic and past
      drug consumption. For several years, it has been possible to determine even the
      intake of ethanol in hair samples by detecting the ethanol metabolites ethyl
      glucuronide or fatty acid ethyl esters. Recently, new requirements were published
      for the use of EtG as an abstinence test (c(EtG) < 7 pg/mg) as well as for heavy
      drinking detection (c(EtG) > 30 pg/mg). In order to perform abstinence tests, a
      sensitive LC-MS/MS procedure has been developed and fully validated according to
      the guidelines of forensic toxicology. The nine-point calibration curve showed
      linearity over the range of concentrations from 2-1,000 pg/mg. Detection and
      quantification limits were 1 and 4 pg/mg respectively. The intra- and inter-day
      precision and accuracy were always better than 20%. The validated procedure has
      successfully been applied to perform abstinence tests and to analyze hair samples
      from persons in withdrawal treatment. Concentrations between <LOQ and 400 pg/mg
      were determined. In some cases, interfering peaks complicated the quantification
      to some extent. First results using varied chromatographic conditions showed
      constituting results. However, modified chromatographic conditions help
      substantiate critical results, especially if the determined EtG concentration is
      close to a cut-off value.

PMID- 20130845
TI  - Residue 826 in the calcium-sensing receptor is implicated in the response to
      calcium and to R-568 calcimimetic compound.
AB  - Within the extracellular loops of the seven-transmembrane domain of the calcium
      sensing receptor (CaR) there is a region (I819-E837) relevant for calcimimetic
      activity. As the naturally occurring variant Ala826Thr is within this important
      region, it may be postulated that this change may influence the CaR response to
      calcium and R-568. Human embryonic kidney (HEK-293) cells transiently transfected
      with three different human CaRs (wild-type [A826], variant allele [T826], and
      artificial mutant [W826]) were used to test the ability of calcium alone or in
      combination with the calcimimetic R-568 to modulate CaR activity. CaR activation
      was detected by flow cytometry using a fluorescent probe. Intracellular calcium
      changes were measured in response to changes in extracellular calcium alone or
      with different R-568 concentrations. The change of the alanine in the 826
      position (A826) for threonine (T826) worsened calcium sensitivity, increasing the
      EC(50) value from 2.34 +/- 0.48 mM (A826, wild-type) to 2.96 +/- 0.75 mM (T826)
      (P < 0.05). The T826 receptor reached a similar response with 1 muM R-568
      compared with the wild-type receptor. On the contrary, the artificial
      introduction of a tryptophan in the same position (W826) did not affect calcium
      sensitivity (EC(50) = 2.64 +/- 0.81 mM) but reduced the ability of the receptor
      to respond to R-568. The results demonstrate the importance of the 826 residue in
      the CaR response to calcium and calcimimetics. Since the A826T change was
      described as a natural variant, the differences in the calcium and calcimimetic
      responses observed between the alleles could have potential clinical impact.

PMID- 20130846
TI  - Differences in the drug prescriptions to children by Italian paediatricians and
      general practitioners.
AB  - PURPOSE: To compare family paediatricians' and general practitioners' habits on
      drug prescribing to children. METHODS: Prescriptions reimbursed by the Health
      Service and dispensed by the retail pharmacies of 15 local health units in the
      Lombardy Region of Italy during 2005 were analysed. Only family paediatricians
      and general practitioners who were in charge of children aged 6-13 years were
      included. RESULTS: During 2005, 239,296 children (43.6% of the selected
      population) received at least one drug prescription. The prevalence was higher in
      children treated by general practitioners (44.2 versus 43.4%), in particular in
      children 13 years old, with a prevalence of 38.7 versus 31.8% in children cared
      for by general practitioners and family paediatricians respectively. The
      prevalence of the most prescribed therapeutic classes was similar in the two
      groups. Some differences were found concerning the antibiotic classes, with
      family paediatricians prescribing penicillins more frequently and general
      practitioners prescribing macrolides and cephalosporins more frequently. A total
      of 542 drugs were prescribed, 78% of which were prescribed by both the family
      paediatricians and the general practitioners. In all, only four drugs were
      prescribed by 75% or more physicians. The chance of receiving a drug
      prescription, adjusted for age, gender and local health unit of residence, was
      slightly higher in children cared for by general practitioners (OR 1.16; 95%CI
      1.14-1.17). CONCLUSIONS: Few differences were found between the prescribing
      patterns of family paediatricians and those of general practitioners. Differences
      exist in particular for older children and for some drug classes.

PMID- 20130847
TI  - Regulation of human and pig renal Na(+),K (+)-ATPase activity by tyrosine
      phosphorylation of their alpha(1)-subunits.
AB  - Modulation of the physiologically influential Na(+),K(+)-ATPase is a complex
      process involving a wide variety of factors. To determine the possible effects of
      the protein tyrosine phosphatase (PTP) inhibitors dephostatin and Et-3,4
      dephostatin on human and pig, renal cells and enzymatic extracts, we treated our
      samples (15 min-24 h) with those PTP inhibitors (0-100 microM). PTP inhibitors
      were found to possess a concentration-dependent inhibition of Na(+),K(+)-ATPase
      activity in both human and pig samples. The inhibition was similarly demonstrated
      on all cellular, microsomal fraction and purified Na(+),K(+)-ATPase levels.
      Despite rigorous activity recovery attempts, the PTP inhibitors' effects were
      sustained on Na(+),K(+)-ATPase activity. Western blotting experiments revealed
      the expression of both alpha(1)- and beta(1)-subunits in both human and pig
      tissues. alpha(1)-Subunits possessed higher tyrosine phosphorylation levels with
      higher concentrations of PTP inhibitors. Meanwhile, serine/threonine residues of
      both alpha(1)- and beta(1)-subunits demonstrated diminished phosphorylation
      levels upon dephostatin treatment. Accordingly, we provide evidence that
      Na(+),K(+)-ATPase can be regulated through tyrosine phosphorylation of primarily
      their alpha(1)-subunits, using PTP inhibitors.

PMID- 20130848
TI  - Melatonin reduces apoptosis induced by calcium signaling in human leukocytes:
      Evidence for the involvement of mitochondria and Bax activation.
AB  - We have evaluated the effect of melatonin on apoptosis evoked by increases in
      [Ca(2+)]( c ) in human leukocytes. Our results show that treatment of neutrophils
      with the calcium mobilizing agonist FMLP or the specific inhibitor of calcium
      reuptake thapsigargin induced a transient increase in [Ca(2+)]( c ). Our results
      also show that FMLP and thapsigargin increased caspase-9 and -3 activities and
      the active forms of both caspases. The effect of FMLP and thapsigargin on caspase
      activation was time-dependent. Similar results were obtained when lymphocytes
      were stimulated with thapsigargin. This stimulatory effect was accompanied by
      induction of mPTP, activation of the proapoptotic protein Bax and release of
      cytochrome c. However, when leukocytes were pretreated with melatonin, all of the
      apoptotic features indicated above were significantly reversed. Our results
      suggest that melatonin reduces caspase-9 and -3 activities induced by increases
      in [Ca(2+)]( c ) in human leukocytes, which are produced through the inhibition
      of both mPTP and Bax activation.

PMID- 20130849
TI  - A transmural gradient in the cardiac Na/K pump generates a transmural gradient in
      Na/Ca exchange.
AB  - We previously demonstrated a transmural gradient in Na/K pump current (I (P)) and
      [Na(+)]( i ), with the highest maximum I (P) and lowest [Na(+)]( i ) in
      epicardium. The present study examines the relationship between the transmural
      gradient in I (P) and Na/Ca exchange (NCX). Myocytes were isolated from canine
      left ventricle. Whole-cell patch clamp was used to measure current generated by
      NCX (I (NCX)) and inward background calcium current (I (ibCa)), defined as inward
      current through Ca(2+) channels less outward current through Ca(2+)-ATPase. When
      resting myocytes from endocardium (Endo), midmyocardium (Mid) or epicardium (Epi)
      were studied in the same conditions, I (NCX) was the same and I (ibCa) was zero.
      Moreover, Western blots were consistent with NCX protein being uniform across the
      wall. However, the gradient in [Na(+)]( i ), with I (ibCa) = 0, should create a
      gradient in [Ca(2+)]( i ). To test this hypothesis, we measured resting [Ca(2+)](
      i ) using two methods, based on either transport or the Ca(2+)-sensitive dye
      Fura2. Both methods demonstrated a significant transmural gradient in resting
      [Ca(2+)]( i ), with Endo > Mid > Epi. This gradient was eliminated by exposing
      Epi to sufficient ouabain to partially inhibit Na/K pumps, thus increasing
      [Na(+)]( i ) to values similar to those in Endo. These data support the existence
      of a transmural gradient for Ca(2+) removal by NCX. This gradient is not due to
      differences in expression of NCX; rather, it is generated by a transmural
      gradient in [Na(+)]( i ), which is due to a transmural gradient in plasma
      membrane expression of the Na/K pump.

PMID- 20130850
TI  - In vitro and immunological assessment of the estrogenic activity and
      concentrations of 17beta-estradiol, estrone, and ethinyl estradiol in treated
      effluent from 45 wastewater treatment plants in Victoria, Australia.
AB  - The project was conducted between May 2006 and September 2007, and involved the
      collection of effluent samples from 45 wastewater treatment plants (WWTPs). The
      45 WWTPs included 16 lagoon-based plants and 29 with activated sludge-based
      processes. Permission was obtained from all the relevant water authorities to
      collect samples of final effluent at point of discharge to the environment,
      whether that was to a creek, a river, the ocean, or the land. Samples were
      collected on two occasions, namely, in August 2006 (winter) and late February
      early March 2007 (summer), and subjected to a number of biological and chemical
      analyses, including toxicity tests, measurement of hormonal (estrogenic) activity
      using yeast-based bioassays, and measurement of specific hormonal concentrations
      using enzyme-linked immunosorbent assays (ELISAs). Almost all of the effluents
      examined showed estrogenic activity: in winter, no activity to 73 ng/l 17beta
      estradiol equivalents (EEQ); and in summer, no activity to 20 ng/l EEQ. On the
      whole, the levels of estrogenic activity observed were comparable with the range
      recently reported in Australia and New Zealand using human estrogen receptor
      based assays ("not detected" to approximately 10 ng/l EEQ). The low/no bioassay
      response was confirmed by the chemical assessment of estradiol, estrone, and
      ethinyl estradiol concentrations by ELISA, which returned concentrations of these
      compounds for the most part below 10 ng/l.

PMID- 20130851
TI  - Uptake and elimination of cadmium and zinc by Eisenia andrei during exposure to
      low concentrations in artificial soil.
AB  - Bioaccumulation factors (BAFs) are often used in the risk assessment process to
      estimate trophic transfer of contaminants such as metals from soil. BAFs can be
      derived from laboratory studies through the determination of steady-state
      concentrations or kinetic estimation methods. In this study, bioaccumulation
      tests were performed with artificial soil spiked at low levels with cadmium or
      zinc to determine uptake and elimination kinetics of both metals by the compost
      worm Eisenia andrei. The metal-amended soils were acclimated for 21 days prior to
      the test, after which worms were individually incubated in the soils. The uptake
      phase comprised 0-21 days, after which the test organisms were transferred into
      clean soil and the elimination phase continued for an additional 21 days.
      Subsamples of soil and earthworms (whole body) were collected from independent
      replicates throughout the uptake phase and elimination phase and analyzed for
      total metal concentrations. Uptake of Cd in E. andrei increased linearly with
      time and did not reach steady state within the testing period. Cd uptake and
      excretion were described by a one-compartment first-order kinetics model. Zn
      concentrations rapidly increased in E. andrei after 1 day of exposure but
      subsequently decreased to background levels throughout the remainder of the
      uptake phase; internal Zn concentrations did not change from background levels
      during the elimination phase. Kinetic BAFs were calculated for Cd and Zn. Cd is a
      nonessential metal that is bioaccumulated at a relatively rapid rate, while Zn is
      an essential metal, and as such, it is regulated by E. andrei. Metal essentiality
      and concentration significantly impact bioaccumulation of metals by terrestrial
      invertebrates.

PMID- 20130852
TI  - Twenty classic hand radiographs that lead to diagnosis.
AB  - Most of the common skeletal dysplasias have some manifestation in the hand. Many
      have characteristic findings in the hand that lead to the diagnosis. Hand bones
      are also affected in many systemic hematologic and metabolic conditions. The
      diagnosis can be clinched on a single hand radiograph if characteristic findings
      are present. This pictorial essay illustrates characteristic findings of 20
      common conditions including bone dysplasias and metabolic and hematologic
      abnormalities on a single hand radiograph. It also includes some common hand
      abnormalities without systemic skeletal abnormalities.

PMID- 20130853
TI  - Identification and characterization of a mosquito pupicidal metabolite of a
      Bacillus subtilis subsp. subtilis strain.
AB  - The culture supernatant of a strain of Bacillus subtilis subsp. subtilis isolated
      from mangrove forests of Andaman and Nicobar islands, India was found to kill
      larval and pupal stages of mosquitoes. A chloroform extract of the culture
      supernatant of the bacterium showed pupicidal effects at an LC(50) dose of 1
      microg/ml. The mosquitocidal metabolite(s) produced by this strain were purified
      by gel permeation chromatography. The purified fraction was subjected to Fourier
      transform infrared (FTIR) spectroscopy and Matrix-assisted laser desorption
      ionization-time of flight (MALDI-TOF) mass spectrometry. The FTIR spectrum of
      active fraction/CHCl3 residue showed strong band characteristic of peptides.
      MALDI-TOF spectrum of the sample showed well-resolved group of peaks at m/z
      values 1,030.6, 1,046.7, 1,044.6, 1,060.5, 1,058.6, 1,058.7, and 1,074.6. The
      results indicated production of different isoforms of surfactin, ranging from C13
      C15. Further, the sfp gene responsible for the production of surfactin was
      amplified and sequenced. In conclusion, this study showed that the mosquito
      pupicidal metabolite(s), produced by B. subtilis subsp. subtilis is the cyclic
      lipopeptide, surfactin. The mode of action of surfactin on pupae of mosquitoes is
      discussed. This is the first report on the mosquito pupicidal activity of
      surfactin produced by B. subtilis subsp. subtilis.

PMID- 20130856
TI  - Extrastriatal uptake on (123)I-ioflupane brain SPECT.

PMID- 20130857
TI  - Does amifostine have radioprotective effects on salivary glands in high-dose
      radioactive iodine-treated differentiated thyroid cancer.
AB  - OBJECTIVES: To assess the effects of amifostine on salivary glands in radioactive
      iodine-treated differentiated thyroid cancer. METHODS: We searched the MEDLINE,
      EMBASE and the Cochrane Library for randomized controlled clinical trials which
      compared the effects of amifostine with those of placebo or acid-stimulating
      agents. RESULTS: Two randomized controlled clinical trials with a total of 130
      patients were included. Both studies had a low risk of bias. There were no
      statistically significant differences between the effects of amifostine and acid
      stimulating agents on the incidence of xerostomia (RR 0.24, 95% CI 0.01 to 9.52),
      the decrease of scintigraphically measured uptake of (99m)Tc by the parotid (RR
      0.30, 95% CI -2.28 to 2.88) or submandibular glands (RR 1.90, 95% CI -1.46 to
      5.26) at 12 months, or the reduction in blood pressure (RR 5.00, 95% CI 0.25 to
      99.16). Neither of the included trials investigated death from any cause,
      morbidity, health-related quality of life or costs. CONCLUSION: The results of
      two randomized controlled clinical trials suggest that amifostine has no
      significant radioprotective effects on salivary glands in radioactive iodine
      treatment of differentiated thyroid cancer. The use of acid-stimulating agents to
      increase salivation should remain the first choice during radioactive iodine
      treatment of differentiated thyroid cancer. Patients should also be well informed
      of the importance of hydration and acid stimulation.

PMID- 20130858
TI  - A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in
      vivo comparison with the 111In-labelled analogue.
AB  - PURPOSE: Overexpression of HER2 receptors is a prognostic and predictive
      biomarker in breast cancer and a number of other malignancies. Radionuclide
      molecular imaging of HER2 overexpression may influence patient management making
      treatment more personalized. Earlier, (111)In-DOTA-Z(HER2:342-pep2) (ABY-002)
      Affibody molecule demonstrated excellent imaging of HER2-expressing xenografts in
      mice shortly after injection. The use of the positron-emitting nuclide (68)Ga
      instead of (111)In might increase both the sensitivity of HER2 imaging and
      accuracy of expression quantification. The goal of this study was to prepare and
      characterize (68)Ga-labelled ABY-002. METHODS: (68)Ga labelling of ABY-002 was
      optimized. In vitro cell binding and procession of (68)Ga-ABY-002 was evaluated.
      Biodistribution and tumour targeting of (68)Ga-ABY-002 and (111)In-ABY-002 was
      compared in vivo by paired-label experiments. RESULTS: ABY-002 was incubated with
      (68)Ga at 90 degrees C for 10 min resulting in a radiochemical labelling yield of
      over 95%. Capacity for specific binding to HER2-expressing cells was retained. In
      vivo, both (68)Ga-ABY-002 and (111)In-ABY-002 demonstrated specific targeting of
      SKOV-3 xenografts and high-contrast imaging. Background radioactivity in blood,
      lungs, gastrointestinal tract and muscle fell more rapidly for (68)Ga-ABY-002
      compared with (111)In-ABY-002 favouring imaging shortly after injection. For
      (68)Ga-ABY-002, a tumour uptake of 12.4 +/- 3.8%ID/g and a tumour to blood ratio
      of 31 +/- 13 were achieved at 2 h post-injection. CONCLUSION: (68)Ga-ABY-002 is
      easy to label and provides high-contrast imaging within 2 h after injection. This
      makes it a promising candidate for clinical molecular imaging of HER2 expression
      in malignant tumours.

PMID- 20130859
TI  - Routine quality control recommendations for nuclear medicine instrumentation.

PMID- 20130860
TI  - Feasibility of FDG PET/CT to monitor the response of axillary lymph node
      metastases to neoadjuvant chemotherapy in breast cancer patients.
AB  - PURPOSE: The aim of this study was to assess the accuracy of (18)F
      fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to visualize lymph
      node metastases before the start of neoadjuvant chemotherapy and to determine how
      often the visualization is sufficiently prominent to allow monitoring of the
      axillary response. METHODS: Thirty-eight patients with invasive breast cancer of
      >3 cm and/or lymph node metastasis underwent FDG PET/CT before neoadjuvant
      chemotherapy. The results of the FDG PET/CT were compared with those from
      ultrasonography with fine-needle aspiration (FNA) cytology or sentinel node
      biopsy. Patients suitable for response monitoring of the axilla were defined as
      having either a maximum standardized uptake value (SUV(max)) >or= 2.5 or a tumour
      to background ratio >or=5 in the most intense lymph node. RESULTS: The
      sensitivity and specificity of FDG PET/CT in detecting axillary involvement were
      97 and 100%, respectively. No difference existed between the SUV(max) of the
      primary tumour and that from the related most intense lymph node metastasis.
      Moreover, the mean tumour to background ratio was 90% higher in the lymph nodes
      compared to the primary tumour (p = 0.006). Ninety-three per cent of the patients
      had sufficient uptake in the lymph nodes to qualify for subsequent response
      monitoring of the axilla. A considerable distinction in metabolic activity was
      observed between the different subtypes of breast cancer. The mean SUV(max) in
      lymph node metastases of oestrogen receptor (ER)-positive, triple-negative and
      human epidermal growth factor receptor 2 (HER2)-positive tumours was 6.6, 11.6
      and 6.6, respectively. CONCLUSION: The high accuracy in visualizing lymph node
      metastases and the sufficiently high SUV(max) and tumour to background ratio at
      baseline suggest that it is feasible to monitor the axillary response with FDG
      PET/CT, especially in triple-negative tumours.

PMID- 20130861
TI  - The anti-tumor effect of Newcastle disease virus HN protein is influenced by
      differential subcellular targeting.
AB  - BACKGROUND: Immunotherapy is emerging as a major player in the current standard
      of care for aggressive cancers such as non-small cell lung cancer (NSCLC). The
      Newcastle disease virus with its tumor-specific replicative and oncolytic
      abilities is a promising immunotherapeutic candidate. A DNA vaccine expressing
      the major immunogenic hemagglutinin-neuraminidase (HN) protein of this virus has
      shown promising results as an immunotherapeutic agent. METHODS: In the present
      study, three different DNA vaccine constructs encoding differentially targeted HN
      proteins (cytoplasmic or Cy-HN, secreted or Sc-HN and membrane-anchored or M-HN)
      were generated to evaluate their anti-tumor effect in vitro and in vivo. RESULTS:
      Although all three DNA constructs elicited an immune response, tumor-bearing mice
      intratumorally injected with M-HN demonstrated a significantly better anti-tumor
      effect than those injected with Cy-HN or Sc-HN. We also showed that this anti
      tumor effect was mediated by higher lymphocyte proliferative response and CTL
      activity in mice intratumorally injected with M-HN. CONCLUSION: The membrane
      anchored form of the HN protein appears to be an ideal candidate to develop as an
      immunotherapeutic agent for NSCLC.

PMID- 20130862
TI  - Chronic groin pain after open, transabdominal preperitoneal and totally
      extraperitoneal hernia repair.

PMID- 20130863
TI  - Five-year follow-up of a randomized clinical trial of unilateral thyroid
      lobectomy with or without postoperative levothyroxine treatment.
AB  - BACKGROUND: The aim of this study was to compare the prevalence of recurrent
      nodular goiter in the contralateral thyroid lobe among patients after unilateral
      thyroid lobectomy for unilateral multinodular goiter (MNG) receiving versus not
      receiving postoperative prophylactic levothyroxine (LT4) treatment. METHODS: From
      January 2000 through December 2003, 150 consenting patients underwent a
      unilateral thyroid lobectomy for unilateral MNG at our institution. They were
      randomized to two groups with 75 patients in each group. Patients in group A
      received prophylactic LT4 treatment postoperatively (dose range 75-125 microg/day
      to maintain thyroid-stimulating hormone values below 1.0 mU/L), whereas patients
      in group B received no postoperative LT4 treatment. All the patients underwent
      ultrasonographic, cytologic, and biochemical follow-up for at least 60 months
      postoperatively. The primary outcome was the prevalence of recurrent goiter in
      the contralateral thyroid lobe. The secondary outcome was the reoperation rate
      for recurrent goiter. The outcomes were stratified according to individual iodine
      metabolism status assessed by urinary iodine excretion. RESULTS: During the 5
      year follow-up, among patients receiving vs. not receiving LT4, recurrent goiter
      within the contralateral thyroid lobe was found in 1.4% vs. 16.7% of patients,
      respectively (p = 0.001). Moreover, 1.4% vs. 8.3%, respectively, of patients
      receiving vs. not receiving LT4 required contralateral thyroid lobe surgery (p =
      0.05). LT4 decreased the recurrence rate among iodine-deficient patients (3.4%
      vs. 36%, respectively; p = 0.002) but not among iodine-sufficient patients (0%
      vs. 6.4%, respectively; p = 0.09). CONCLUSIONS: Prophylactic LT4 treatment
      significantly decreased the recurrence rate of nodular goiter in the
      contralateral thyroid lobe and the need for completion thyroidectomy, mostly
      among patients with iodine deficiency.

PMID- 20130864
TI  - Letter to the editor: Breast cancer in young women in Africa: are there genetic
      and clinical differences with European ancestry patients?

PMID- 20130865
TI  - Prophylactic cholecystectomy in midgut carcinoid patients.
AB  - BACKGROUND: Patients with midgut carcinoid (MGC) tumors are commonly treated with
      somatostatin analogs. Adverse effects of these drugs include impairment of
      gallbladder function, formation of gallstones, and cholecystitis. Prophylactic
      cholecystectomy has been advocated, but data to support this recommendation are
      sparse. We have analyzed a cohort of 235 patients with MGC focusing on the risk
      for gallstone formation and complications thereof. METHODS: Forty-eight of the
      235 patients had been cholecystectomized before surgery for MGC. Of the remaining
      187 patients, 144 were treated with somatostatin analogs. Eighteen of the 187
      patients had their gall bladder removed during the primary carcinoid surgery.
      RESULTS: Twenty-two of the 144 somatostatin-analog-treated patients developed
      complications, such as gallbladder empyema (n = 1), cholangitis (n = 2), acute
      cholecystitis (n = 6), acute pancreatitis (n = 1) or acute pancreatitis and
      cholecystitis (n = 1), or biliary colic (n = 11). Ninety-two of the 144 were
      examined during surgery, by computed tomography, or by ultrasound, most for
      reasons other than gallbladder-related indications, and 63% (58/92) of these
      examinations revealed gallstones. Of the 43 patients not treated with
      somatostatin analogs, only 3 patients suffered from biliary colic and underwent
      cholecystectomy. CONCLUSIONS: In our study the incidence of gallstone-related
      complications seems to be higher than in the general population. We recommend
      that prophylactic cholecystectomy is liberally performed during laparotomy for
      MGC if patients are planned to undergo treatment with somatostatin analogs.

PMID- 20130866
TI  - Heat shock protein expression during cardiac surgery.

PMID- 20130867
TI  - Enhanced intracellular heat shock protein 70 expression of leukocytes and serum
      interleukins release: comparison of on-pump and off-pump coronary artery surgery.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) employing cardiopulmonary
      bypass (CPB; "on-pump" technique) is known to induce a systemic inflammatory
      response and heat-shock protein 70 kDa (HSP70) expression. The objective of the
      present study was to investigate the perioperative intracellular HSP70 expression
      of leukocytes and serum interleukin (IL) release in CABG conducted with both on
      pump and off-pump techniques. METHODS: Thirty-seven patients referred for
      elective CABG were enrolled in this study. These patients were categorized into
      the following three groups: on-pump cardioplegic arrest (n = 12); on-pump beating
      heart (n = 13); and off-pump (n = 12). Blood samples were collected at four time
      points during the perioperative period. Enzyme-linked immunosorbent assay (ELISA)
      was used to determine the serum level of IL-8, IL-10, IL-12, and HSP70. Flow
      cytometric analysis of intracellular HSP70 was performed in populations of
      lymphocytes, monocytes, and granulocytes. RESULTS: The clinical outcomes were
      comparable among the three groups. Elevated serum IL-8, IL-10, IL-12 were found
      in all three groups during the perioperative period. Serum HSP70 was elevated in
      all three groups and was significantly lower in the off-pump group than in the on
      pump cardioplegic arrest and on-pump beating-heart groups. Heat shock protein-70
      expression was found in leukocytes and showed a faster response in monocytes and
      granulocytes than in lymphocytes. The inflammatory response in the off-pump group
      was less than in either of the on-pump groups. CONCLUSIONS: During the
      perioperative period, activation of inflammatory response was associated with
      enhanced expression of HSP70 within leukocytes in CABG patients.

PMID- 20130868
TI  - Impact of prophylactic central neck lymph node dissection on early recurrence in
      papillary thyroid carcinoma.
AB  - BACKGROUND: Although the role of prophylactic central neck lymph node dissection
      (CNLD) in the treatment of papillary thyroid carcinoma (PTC) is controversial,
      many surgeons perform routine prophylactic CNLD. The present study compares local
      recurrence rates in PTC patients undergoing total thyroidectomy with and without
      prophylactic CNLD. MATERIALS AND METHODS: A retrospective review of 206 patients
      undergoing thyroidectomy for PTC was conducted at two tertiary referral centers.
      Of these, 81 patients had total thyroidectomy for PTC and a follow-up between 2
      and 9 years with a mean of 3.1 years. Of these 81 patients, 45 underwent routine
      prophylactic CNLD and 36 did not. For those two groups, demographics, clinical
      and pathologic findings, radioactive iodine (RAI) treatment, and the incidence of
      recurrence were compared. Univariate statistical analysis was performed. RESULTS:
      There was no significant difference in age, gender, multifocality, or
      extrathyroidal extension for the two groups. Patients with CNLD had an average
      tumor size of 1.4 cm versus 2 cm in the group without CNLD (p < 0.05). Patients
      who underwent CNLD had an average of 8 nodes removed, and positive nodes were
      found in 33%. Patients with CNLD received a higher dose of RAI, 102.7 mCi versus
      66.3 mCi (p < 0.05). The incidence of positive nodes correlated with an increased
      RAI dose (r = 0.55). Rates of parathyroid removal and autotransplantation were
      higher in the CNLD group, 36 and 16% in the CNLD group versus 22 and 3% in the
      group without CNLD (p = 0.4 and p = 0.07). Rates of temporary hypocalcemia were
      higher in the CNLD group (31 versus 5%; p = 0.001), however rates of permanent
      hypocalcemia were similar, 1/35 in the no CNLD group versus 0/45 in the CNLD
      group (p = 0.4). There was a higher recurrence rate among patients without CNLD
      6/36 (16.7%) versus 2/45 (4.4%), although this difference was not statistically
      significant (p = 0.13). CONCLUSIONS: Routine CNLD as an adjunct to total
      thyroidectomy identifies positive nodes in over 30% of patients with PTC. The
      discovery of positive nodes is associated with higher doses of RAI for
      postoperative ablation, and there is a trend toward decreased recurrence in
      patients undergoing CNLD.

PMID- 20130870
TI  - Removal of autografted parathyroid tissue for recurrent renal hyperparathyroidism
      in hemodialysis patients.
AB  - BACKGROUND: Recurrent renal hyperparathyroidism (HPT) is a serious problem after
      parathyroidectomy (PTx). We evaluated the frequency of graft-dependent recurrent
      HPT and the clinical outcomes after removal of the autograft. METHODS: Between
      March 1980 and January 2009, 2660 patients underwent total PTx with forearm
      autograft. After resection of all parathyroid glands, 30 pieces of 1 x 1 x 3 mm
      parathyroid tissue from diffuse hyperplasia, if possible, were autografted into
      brachioradial muscle. Graft-dependent recurrence of HPT was diagnosed by a high
      PTH gradient and detection of swollen autografts by palpation and/or MRI or US.
      RESULTS: In 248/2660 (9.3%) patients, removal of the graft was required a total
      of 327 times (53 patients required removal of the autograft several times). The
      cumulative frequency of graft-dependent recurrent HPT was 17.4% ten years after
      the initial PTx. Thirty-two patients underwent both resection of missed glands
      located in the neck or mediastinum and removal of the graft. En-bloc resection of
      autograft with surrounding muscle was required to avoid reoperation. When the
      intact PTH level dropped under 300 pg/ml, in the majority of patients renal HPT
      could be medically managed after the operation. The mean weight of the resected
      parathyroid tissue was 1583.7 mg. No specimen had histopathologically malignant
      features. Three patients suffered from hematoma in the wound. CONCLUSIONS: Graft
      dependent recurrent renal HPT is not negligible. However, in the majority of
      patients, renal HPT can be controlled by removal of the autograft noninvasively.
      Total PTx with forearm autograft is preferable for hemodialysis patients,
      especially when long-term survival is expected.

PMID- 20130871
TI  - The incidence and success of treatment for severe chronic groin pain after open,
      transabdominal preperitoneal, and totally extraperitoneal hernia repair.
AB  - BACKGROUND: Chronic groin pain (CGP) is a significant cause of postoperative
      morbidity after inguinal hernia repair. Open, transabdominal preperitoneal
      (TAPP), and totally extraperitoneal (TEP) repair are all commonly performed
      methods of herniorrhaphy. The aim of this study was to compare the frequency of
      attendance at a chronic pain clinic (CPC) for CGP after open, TAPP or TEP repair.
      METHODS: A retrospective review of all inguinal hernia repairs between January
      1997 and December 2006 identified patients attending the CPC for CGP post
      herniorrhaphy. In this study CGP post-herniorrhaphy was defined as pain that
      limited daily activities despite simple analgesia thereby requiring referral to
      the specialist CPC following surgical review. RESULTS: A total of 8513 patients
      underwent 9607 inguinal hernia repairs; 6497 (75.5%) were open, 1916 (22.3%) were
      TAPP, and 198 (2.3%) were TEP. Of these, 46 (0.71%) open, 22 (1.15%) TAPP, and 6
      (3.03%) TEP repairs required attendance at CPC. A statistically significant
      difference in frequency of CPC attendance following laparoscopic versus open (P =
      0.008), TEP versus open (P < or = 0.001), and TEP versus TAPP repair (P = 0.027)
      was observed. After an average of 1 year, 69% of patients were discharged symptom
      free from the CPC. In 16%, CGP resolved prior to CPC attendance. CONCLUSIONS: In
      contrast to previous reports, laparoscopic hernia repair is associated with a
      greater frequency of attendance at CPC than open repair, a finding that merits
      further investigation. Of those requiring treatment, the majority were discharged
      pain-free after an average of 1 year.

PMID- 20130872
TI  - Multiple coaxial catheter system for reliable access in interventional stroke
      therapy.
AB  - In some patients with acute cerebral vessel occlusion, navigating mechanical
      thrombectomy systems is difficult due to tortuous anatomy of the aortic arch,
      carotid arteries, or vertebral arteries. Our purpose was to describe a multiple
      coaxial catheter system used for mechanical revascularization that helps
      navigation and manipulations in tortuous vessels. A triple or quadruple coaxial
      catheter system was built in 28 consecutive cases presenting with acute ischemic
      stroke. All cases were treated by mechanical thrombectomy with the Penumbra
      System. In cases of unsuccessful thrombo-aspiration, additional thrombolysis or
      angioplasty with stent placement was used for improving recanalization. The
      catheter system consisted of an outermost 8-Fr and an intermediate 6-Fr guiding
      catheter, containing the inner Penumbra reperfusion catheters. The largest, 4.1
      Fr, reperfusion catheter was navigated over a Prowler Select Plus microcatheter.
      The catheter system provided access to reach the cerebral lesions and provided
      stability for the mechanically demanding manipulations of thromboaspiration and
      stent navigation in all cases. Apart from their mechanical role, the specific
      parts of the system could also provide access to different types of
      interventions, like carotid stenting through the 8-Fr guiding catheter and
      intracranial stenting and thrombolysis through the Prowler Select Plus
      microcatheter. In this series, there were no complications related to the
      catheter system. In conclusion, building up a triple or quadruple coaxial system
      proved to be safe and efficient in our experience for the mechanical thrombectomy
      treatment of acute ischemic stroke.

PMID- 20130873
TI  - Ultrasound-guided percutaneous drainage of neonatal pyometrocolpos under local
      anesthesia.
AB  - Hydrometrocolpos is an uncommon congenital disorder with cystic dilatation of the
      vagina and uterus that occurs as a result of accumulated secretions from the
      reproductive tract due to distal genital tract obstruction. Secondary infection
      may also occur, resulting in pyometrocolpos, a potentially lethal disease.
      Immediate drainage of the cystic mass in patients determined to have
      pyometrocolpos is required to prevent or treat uropathy and septicemia until
      definitive corrective surgery can be performed. We report an unusual cause of
      obstructive uropathy in three infants: pyometrocolpos due to lower genital tract
      atresia. Ultrasound-guided percutaneous drainage of the pyometrocolpos resulted
      in dramatically improved clinical and laboratory findings in these patients.
      Ultrasound-guided percutaneous drainage under local anesthesia is a simple,
      minimally invasive, safe, and effective procedure that facilitates later
      successful corrective surgery and avoids the need for more complex drainage
      procedures.

PMID- 20130874
TI  - Cutaneous bronchobiliary fistula treated with Tissucol sealant.
AB  - Bronchobiliary fistula is a rare and is an uncommon but severe complication of
      hydatid disease of the liver. Treatment has traditionally been surgical
      resection, but embolization and stent placement have been described. The invasive
      method seems to be a key component of patient treatment. We describe a case of a
      58-year-old woman who, 25 years before, had undergone surgery for a hydatid cyst.
      A total cystectomy without previous puncture or parasite extraction was carried
      out. The lower aspect of the cyst was found to be completely perforated over the
      biliary duct. During the postoperative course, the patient had subphrenic right
      sided pleural effusion and biliary fistula that subsided with medical treatment.
      Afterward, the patient came to the outpatient area of our hospital complaining of
      leakage of purulent exudate through the cutaneous opening, pain located on the
      right hypochondrium radiating to the right hemithorax, malaise, fever, chronic
      cough, and occasional vomiting of bile. Fistulography revealed an anfractuous
      cavity communicating with a residual cystic cavity on the right hepatic lobe. We
      observed communication with the intrahepatic canaliculi. Computed tomographic
      scan revealed a fistulous tract on the anterior liver border through the
      abdominal wall. There were no posttreatment complications. The patient is
      asymptomatic.

PMID- 20130875
TI  - Quality improvement for portal vein embolization.

PMID- 20130876
TI  - A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory
      metastatic pancreatic cancer.
AB  - PURPOSE: No standard of care exists for patients with metastatic pancreatic
      cancer following progression on first-line chemotherapy. Based on potential for
      additive or synergistic activity by concurrent inhibition of VEGF and EGFR, we
      conducted a phase II study evaluating the combination of bevacizumab plus
      erlotinib in this patient population. METHODS: Patients with metastatic
      pancreatic adenocarcinoma, ECOG performance status 0-1, and previous exposure to
      1-3 systemic therapies (at least one gemcitabine-based) were eligible. Treatment
      consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily.
      RESULTS: Thirty-six patients were enrolled, including eight who had previously
      received VEGF-targeted therapy and nine prior erlotinib. Median number of
      treatment cycles was 2 (range, 1-7). Common toxicities included rash (72%),
      diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). One
      patient demonstrated partial response and seven others stable disease for >2
      cycles. CA19-9 decline >=25% was observed in 4/26 patients with baseline levels
      >2x ULN. Estimated median time to progression was 40 days (95% CI, 35-41 days)
      and median survival 102 days (95% CI, 74-117 days), with a 6-month survival rate
      of 22%. Baseline concentration of circulating endothelial cells (CD45(
      )/CD34(+)/CD31(+)) was inversely associated with overall survival. CONCLUSIONS:
      The combination of bevacizumab and erlotinib is safe but relatively ineffective
      in patients with gemcitabine-refractory metastatic pancreatic cancer. Future
      studies should focus on refining subsets of patients in this challenging
      population likely to benefit from treatment beyond first-line.

PMID- 20130878
TI  - Carboplatin with weekly docetaxel and ifosfamide in advanced head and neck
      cancers: a phase I Brown University Oncology Group dose escalation study (HN-93).
AB  - PURPOSE: A phase I study was performed to determine the maximally tolerated dose
      of carboplatin, ifosfamide, and docetaxel in advanced head and neck cancers.
      METHODS: Carboplatin (week 1) was administered with weekly docetaxel and
      ifosfamide for 3 weeks in an every 4-week cycle. Restaging was done after two
      cycles, while dose level escalation was done in cohorts of three patients.
      RESULTS: Fifteen patients (recurrent/metastatic disease, n = 8; bulky locally
      advanced disease, n = 7) were enrolled. No dose-limiting toxicities were
      observed. Toxicities included grade 3 neutropenia and anemia (n = 2, each), and
      grade 2 thrombocytopenia (n = 3). The final level of carboplatin AUC = 6 (week 1)
      with docetaxel 30 mg/m(2) per week and ifosfamide 1,000 mg/m(2) per week was
      chosen for further evaluation. CONCLUSIONS: This novel regimen of carboplatin
      with weekly docetaxel and ifosfamide has a favorable toxicity profile and is
      active in this setting. Phase II study results are awaited.

PMID- 20130877
TI  - A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or
      without radiation therapy in patients with gastric cancer.
AB  - The optimal adjuvant treatment for gastric cancer remains controversial. We
      compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen,
      in patients with high-risk gastric cancer, with that of the same chemotherapy
      plus radiation therapy (RT). In addition, we evaluated the prognostic and/or
      predictive value of a panel of molecular markers. Patients with histologically
      proven, radically resected gastric cancer, stage > or =T3 and/or N+ were
      randomized to 6 cycles of docetaxel with cisplatin, both at 75 mg/m2 every 3
      weeks (arm A) or the same treatment with RT (arm B; 45 Gy). Due to excessive
      nausea and vomiting, cisplatin was substituted by carboplatin at AUC (area under
      the curve) of 5 after the first 45 patients (22 group A, 23 group B). The
      prognostic value of EGFR, ERCC1, HER2, MET/HGFR, MAP-Tau, and PTEN expression was
      also studied in a subset of 67 patients using immunohistochemistry on tissue
      microarrays (TMAs). A total of 147 patients were randomized. After a median
      follow-up of 53.7 months, no differences in overall (OS) and disease-free
      survival (DFS) were found between the two arms. The most common grade 3/4
      toxicities for arms A and B (excluding alopecia) were non-febrile neutropenia (11
      and 17%, respectively), febrile neutropenia (9 and 7%) and diarrhea (7 and 4%,
      respectively). Patients with ERCC1 positive tumors had significantly longer
      median DFS (33.1 vs. 11.8 months, Wald P = 0.016) and OS (63.2 vs. 18.8 months,
      Wald P = 0.046). Our results indicate that the addition of RT to
      platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in
      high-risk, radically resected gastric cancer. However, the possibility that a
      benefit by the addition of RT was not detected due to decreased power of the
      study should not be excluded.

PMID- 20130879
TI  - Phase II study of pemetrexed in patients with advanced neuroendocrine tumors.
AB  - PURPOSE: In some reports, 5-fluorouracil has been associated with modest activity
      in patients with neuroendocrine tumors. Pemetrexed is a multitargeted antifolate
      with activity in tumor types not significantly responsive to other antifolates.
      We evaluated the efficacy of pemetrexed in a phase II study of patients with
      advanced neuroendocrine tumors. METHODS: Patients with metastatic neuroendocrine
      tumors (excluding small-cell carcinoma) were treated with pemetrexed administered
      intravenously at a dose of 500 mg/m(2) every 21 days. To reduce potential
      toxicity, patients also received folic acid, vitamin B12 supplementation, and
      peri-infusional treatment with dexamethasone. Patients were followed for
      response, toxicity, and survival. RESULTS: The study was designed with a total
      accrual goal of 32 patients. Due to lack of radiographic responses in patients
      during the study period, accrual was terminated at 17. However, one patient
      achieved a delayed partial response following discontinuation of pemetrexed. Ten
      patients were evaluable for biochemical response; five (50%) experienced >50%
      decrease in plasma chromogranin A. Among the 17 patients, 5 (29%) discontinued
      therapy due to treatment-related toxicity. The median overall survival was 12.1
      months. CONCLUSION: Pemetrexed does not appear to have significant antitumor
      activity in patients with advanced neuroendocrine tumors. The limited antitumor
      activity and potential toxicity associated with pemetrexed mirrors experience
      with the majority of other cytotoxic agents in patients with neuroendocrine
      tumors. Investigation of novel, molecularly targeted agents may offer more
      promise in this disease.

PMID- 20130880
TI  - Contralateral electroacupuncture pretreatment suppresses carrageenan-induced
      inflammatory pain via the opioid-mu receptor.
AB  - Acupuncture has been used to treat various clinical diseases in Eastern medicine.
      To investigate the analgesic effect of electroacupuncture (EA) pretreatment on
      carrageenan-induced inflammatory pain, we studied on the effect of EA parameters
      on an animal model of acute arthritic pain. Pretreatment with 1 mA, 10 Hz EA
      prior to carrageenan injection under halothane anesthesia suppressed carrageenan
      induced pain. Interestingly, EA stimulation of the 'Zu-San-Li' (ST36) acupuncture
      point (1 mA, 10 Hz) contralateral to the site of the carrageenan injection in the
      rat synovial cavity produced significantly greater improvement of the weight
      bearing force compared with EA stimulation of the 'San-Yin-Jiao' acupuncture
      point. To determine how ST36 EA treatment suppresses carrageenan-induced
      inflammatory pain, we examined the effect of a mu opioid receptor antagonist on
      ST36 EA-induced analgesia. The selective antagonist of the mu opioid receptor
      (OR) significantly suppressed contralateral ST36 EA-induced analgesia against
      carrageenan-induced inflammation. These results suggested that the analgesic
      effect mediated by the mu OR during low-frequency contralateral EA pretreatment
      has an anti-nociceptive action against inflammatory pain and that it may provide
      a potential strategy to treat inflammatory arthritic pain.

PMID- 20130881
TI  - Pattern and outcome of vascular involvement of Omani patients with Behcet's
      disease.
AB  - The objective of the study is to study the pattern, frequency and outcome of
      vascular events in Omani patients with Behcet's disease (BD). Forty BD patients
      were recruited. Clinical data parameters were recorded, including age at onset,
      disease duration, current disease activity, and the vascular manifestations of
      the disease (current and past events). Disease activity was assessed by ESR, CRP
      and also clinically. For venous and arterial thrombotic events, imaging studies,
      such as Doppler ultrasonography, angiography, MRI, CT, and echocardiography were
      performed. Nine patients had vascular events (23%). The mean age of these
      patients at diagnosis of the vascular event was 24 years (range 15-37) and the
      mean disease duration at onset of the vascular event was 3.8 years (range 3-5);
      this was significant when compared with patients without thrombosis (P=0.001,
      Mann-Whitney test). In these patients with vascular involvement, two patients
      (22%) had venous lesions, three (33%) patients had arterial lesions and four
      patients (44%) had mixed lesions. Two patients (22%) had pulmonary artery
      aneurysm (PAA) and concomitant intracardiac thrombus, and further one patient
      also had PAA. Immunosuppressive therapy resulted in the resolution of PAA and
      intracardiac thrombous. In conclusion, the frequency of vascular complications of
      BD in our patients is similar to those reported around the world. We found
      younger male patients with short disease duration are at a greater risk of
      developing thrombosis. Medical treatment with immunosuppressive therapy without
      anticoagulation seems successful in treating PAA and intracardiac thrombus.

PMID- 20130882
TI  - Simultaneous silencing of FAD2 and FAE1 genes affects both oleic acid and erucic
      acid contents in Brassica napus seeds.
AB  - The fatty acid composition in the seed oil was significantly modified following
      the introduction of transgenes. To further enhance the desirable characteristics
      of rapeseed oil, it would be beneficial to develop a new approach for the
      simultaneous silencing of two or more target genes. Our goals in the current
      study were to (1) increase oleic acid to more than 75%, (2) reduce
      polyunsaturated fatty acids (PUFA) to about 10% and erucic acid to zero, and (3)
      accomplish these changes in a single-transformation event. In a single
      transformation, two fragments amplified from the fatty acid (Delta12)-desaturase
      2 (BnaFAD2) and fatty acid elongase 1 (BnaFAE1) genes of Brassica napus were
      linked together to form a fusion fragment. The fusion fragment was then used to
      assemble unique intron-spliced hairpin interfering constructs. In the transgenic
      plant FFRP4-4, the expression of BnaFAD2 and BnaFAE1 genes was completely
      inhibited. The composition of oleic acid in FFRP4-4 rose to 85%, PUFA dropped to
      10% and erucic acid was undetectable. All hybrid F(1) seeds obtained from the
      reciprocal crossing of FFRP4-4 and GX-parents (with different genetic
      backgrounds) contained more than 80% oleic acid, about 10% PUFA and very low, or
      undetectable, erucic acid. The results confirmed that the fusion fragment
      silencing construct can simultaneously and effectively silence the target genes
      on a consistent basis. The strategy provides a useful tool for detecting gene
      function and advancing genetic engineering techniques for the improvement of
      agricultural crops.

PMID- 20130883
TI  - Two Arabidopsis cyclin A3s possess G1 cyclin-like features.
AB  - A-type cyclins (CYCAs) are a type of mitotic cyclin and are closely related to
      cyclin B. Plant CYCAs are classified into three subtypes (CYCA1-CYCA3), among
      which CYCA3 has been suggested to show a biased expression during the G1-to-S
      phase. We characterised Arabidopsis CYCA3s (CYCA3;1-CYCA3;4) in terms of
      expression pattern and protein function. CYCA3;1 and CYCA3;2 transcripts were
      highly accumulated at the G1/S phase, whereas CYCA3;4 was constantly expressed
      during the cell cycle. Expressions of CYCA3;1 and CYCA3;2 were observed in
      actively dividing tissues, such as root and shoot apical meristems and lateral
      root primordia. Overexpression of CYCA3;1 or CYCA3;2 distorted apical dominance
      in Arabidopsis, indicating that they have critical functions in shoot meristems.
      In insect cells, CYCA3;1 formed an active kinase complex with CDKA;1, an
      orthologue of the yeast Cdc2/Cdc28p, and phosphorylated retinoblastoma-related
      protein, a key regulator in the transition from the G1 to the S phase. Our
      results suggest that Arabidopsis CYCA3;1 and CYCA3;2 are distinct members of the
      G1 cyclin family that play an important role in meristematic tissues.

PMID- 20130884
TI  - Impact of patient age on outcome following bladder-preserving treatment for non
      muscle-invasive bladder cancer.
AB  - OBJECTIVES: To determine the impact of patient age on outcome following bladder
      preserving treatment for non-muscle-invasive bladder cancer (NMIBC). METHODS:
      This study examined 491 patients treated with transurethral resection and/or
      intravesical bacillus Calmette-Guerin (BCG) therapy for primary NMIBC at our
      institution between 1985 and 2005. The patients' age at treatment was classified
      into categories of younger than 50, 50-59, 60-69, 70-79, and 80 years or older.
      Recurrence-free survival and progression-free survival were estimated by the
      Kaplan-Meier method and analyzed using Cox proportional hazard models. RESULTS:
      Tumors of broad-based, multiple, and higher grades were more frequent with
      increasing patient age. Intravesical BCG therapy was less frequently performed on
      elderly patients. At a median follow-up of 45 months, patients 80 years or older
      had the lowest recurrence-free survival and progression-free survival among the
      age groups (log-rank P < 0.001 and P = 0.019, respectively). On Cox proportional
      hazard model, age was an independent risk factor for tumor recurrence and
      progression after controlling for all confounding variables. The recurrence risk
      was 2.3 times higher for patients 80 years or older than those aged 60-69 years
      (P < 0.001). CONCLUSIONS: Older age adversely affected the outcome of patients
      with NMIBC, which is particularly apparent in patients 80 years or older. Further
      prospective studies to confirm these findings are warranted.

PMID- 20130885
TI  - Outcome of treatment of bladder cancer: a comparison between low-volume hospitals
      and an oncology centre.
AB  - PURPOSE: To evaluate the effect of volume of cystectomies in the Greater
      Amsterdam region on postoperative outcomes. METHODS: All primary bladder tumours
      diagnosed between 1989 and 2003 were selected from the Amsterdam Cancer Registry,
      a population-based cancer registry (population 3.0 million). For all patients who
      underwent cystectomy during 1989-2003 at 20 participating hospitals, medical
      records were reviewed for information on postoperative mortality, locoregional
      recurrences and relative risk of death. To assess the effect of volume, outcomes
      at an oncology centre and low-volume hospitals were compared. RESULTS: During
      1989-2003 a total of 1,185 cystectomies were performed in 20 hospitals of the
      Greater Amsterdam region. Postoperative mortality was 3.2%. During 1989-1997, 8%
      of cystectomies were performed at the oncology centre, increasing to 30% in 1998
      2003. Although postoperative mortality at this centre decreased from 4.0% in 1989
      1997 to 1.1% in 1998-2003, the latter percentage was not statistically
      significantly different from the other hospitals during 1998-2003 (OR 0.3; P =
      0.09). No statistically significant difference in locoregional recurrence rate
      and in the relative risk of death was observed between the oncology centre and
      all other hospitals combined. CONCLUSIONS: We observed a lower postoperative
      mortality rate in the oncology centre compared to the low-volume hospitals;
      however, this difference did not reach statistical significance. We could neither
      prove a statistically significant relation between hospital volume, local
      recurrence rate and survival after cystectomy. To answer the question if
      centralisation of cystectomies is beneficial more procedures have to be compared.

PMID- 20130886
TI  - [Technologies, techniques and tactics for micro-incision cataract surgery].
AB  - Ultra-sound (US) phaco-emulsification is currently developing from a small
      incision to a micro-incision cataract surgery (MICS). Improvements in machine
      technologies with new US delivery modes with better control of irrigation and
      aspiration, with smaller phacotips and sleeves and with new intraocular lenses
      and injector systems for implantations through incisions less than 2 mm wide.
      Therefore, the most suitable method for surgery can be selected for each
      individual eye situation. Further improvements of intra-ocular lenses for
      implantation through incisions less than 2 mm wide would be desirable.

PMID- 20130887
TI  - Long-term outcomes of triangle tilt surgery for obstetric brachial plexus injury.
AB  - AIM: The purpose of this study was to evaluate long-term shoulder functional
      outcomes from a triangle tilt procedure on obstetric patients, who initially
      presented with medial rotation contracture and scapular deformity secondary to
      obstetric brachial plexus injury. METHODS: We retrospectively studied long-term
      outcomes both functionally and anatomically in 61 patients (age ranging from 2 to
      12 years). Functional movements were evaluated and scored using a modified Mallet
      scale at different time intervals: preoperatively, 1 year and 2 year following
      triangle tilt surgery. Shoulder anatomy was examined on radiologic images to
      evaluate the severity of shoulder deformities preoperatively and anatomical
      improvement after the surgery. RESULTS: All shoulder functional movements were
      significantly improved at 1 and 2 year follow-ups. Functional improvements were
      maintained in shoulder abduction, external rotation and hand-to-mouth movements
      beyond the first year, and continued in hand-to-neck and hand-to-spine movements
      past 2 years. Remarkable glenohumeral remodeling or reservation of glenoid
      congruence was observed in all patients over a mean time of 27 months
      postoperatively. CONCLUSION: The triangle tilt procedure, which addresses
      scapular and glenohumeral joint abnormalities characteristic of Erb's palsy,
      improves shoulder functional movements and anatomical structure in patients over
      the long-term.

PMID- 20130888
TI  - Prognostic value of galectin-3, a novel marker of fibrosis, in patients with
      chronic heart failure: data from the DEAL-HF study.
AB  - AIMS: Biomarkers are increasingly being used in the management of patients with
      chronic heart failure (HF). Galectin-3 is a recently developed biomarker
      associated with fibrosis and inflammation, and it may play a role in cardiac
      remodeling in HF. We determined its prognostic value in patients with chronic HF.
      METHODS AND RESULTS: Patients with chronic HF (New York Heart Association
      functional class III or IV) who participated in the Deventer-Alkmaar heart
      failure study were studied. Galectin-3 levels were determined at baseline using a
      novel optimized enzyme-linked immunosorbent assay. Univariate and multivariate
      analyses were used to determine the prognostic value of this biomarker. We
      studied 232 patients; their mean age was 71 +/- 10 years, 72% were male, and 96%
      were in NYHA class III. During a follow-up period of 6.5 years, 98 patients died.
      Galectin-3 was a significant predictor of mortality risk after adjustment for age
      and sex, and severity of HF and renal dysfunction, as assessed by NT-proBNP and
      estimated glomerular filtration rate, respectively (hazard ratio per standard
      deviation 1.24, 95% CI 1.03-1.50, P = 0.026). CONCLUSION: Plasma galectin-3 is a
      novel prognostic marker in patients with chronic HF. Its prognostic value is
      independent of severity of HF, as assessed by NT-proBNP levels, and it may
      potentially be used in the management of such patients.

PMID- 20130889
TI  - Percutaneous successful closure of dual atrial septal defect with two Amplatzer
      septal occluder devices.
AB  - We report a case of percutaneous dual atrial septal defect closure with two
      Amplatzer septal occluder devices.

PMID- 20130890
TI  - Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and
      isolated failing human myocardium.
AB  - Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of
      spontaneous circulation (ROSC) and contributes to hemodynamic instability and low
      survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has
      been shown to significantly improve neurologic recovery and survival rates. In
      the present study we investigate the influence of therapeutic hypothermia on
      hemodynamic parameters in resuscitated patients and on contractility in failing
      human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors
      during the hypothermia period. The initial LVEF was 32.6 +/- 1.2% indicating a
      significantly impaired LV function. During hypothermia induction, the infusion
      rate of epinephrine could be significantly reduced from 9.1 +/- 1.3 microg/min
      [arrival intensive care unit (ICU) 35.4 degrees C] to 4.6 +/- 1.0 microg/min (34
      degrees C) and 2.8 +/- 0.5 microg/min (33 degrees C). The dobutamine and
      norepinephrine application rates were not changed significantly. The mean
      arterial blood pressure remained stable. The mean heart rate significantly
      decreased from 91.8 +/- 1.7 bpm (arrival ICU) to 77.3 +/- 1.5 bpm (34 degrees C)
      and 70.3 +/- 1.4 bpm (33 degrees C). In vitro we investigated the effect of
      hypothermia on isolated ventricular muscle strips from explanted failing human
      hearts. With decreasing temperature, the contractility increased to a maximum of
      168 +/- 23% at 27 degrees C (n = 16, P < 0.05). Positive inotropic response to
      hypothermia was accompanied by moderately increased rapid cooling contractures as
      a measure of sarcoplasmic reticulum (SR) Ca(2+) content, but can be elicited even
      when the SR Ca(2+) release is blocked in the presence of ryanodine. Contraction
      and relaxation kinetics are prolonged with hypothermia, indicating increased
      Ca(2+) sensitivity as the main mechanism responsible for inotropy. In conclusion,
      mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might
      contribute to improved survival rates in these patients. Mechanistically, we
      demonstrate that hypothermia improves contractility in failing human myocardium
      most likely by increasing Ca(2+)-sensitivity.

PMID- 20130891
TI  - Folates in bread: retention during bread-making and in vitro bioaccessibility.
AB  - BACKGROUND: Bread is an important folate source in several countries. However,
      bread-making was reported to cause losses of endogenous bread folates
      (approximately 40%) as well as added synthetic folic acid (approximately 30%).
      Furthermore, the bread matrix is suggested to inhibit absorption of folates.
      PURPOSE: To (1) estimate retention of both, endogenous folates and synthetic
      fortificants, during bread-making, (2) assess in vitro folate bioaccessibility
      from breads and a breakfast meal and (3) assess in vitro folate uptake. METHODS:
      Retention of folate forms was assessed by preparing fortified (folic acid and
      [6S]-5-CH(3)-H(4)folate) wholemeal breads and collect samples from dough, proofed
      dough and the bread. In vitro folate bioaccessibility was assessed using the TNO
      gastrointestinal model TIM. In vitro folate uptake was assessed using a novel
      Caco-2 cell/stable isotope model. Folate content in samples was measured using
      LCMS. RESULTS: Bread-making resulted in losses of 41% for endogenous folates and
      up to 25 and 65% for folic acid and [6S]-5-CH(3)-H(4)folate fortificant,
      respectively. 75% of endogenous bread folates and 94% of breakfast folates were
      bioaccessible as assessed by TIM. From [6S]-5-CH(3)-H(4)folate-fortified bread,
      relative folate uptake into Caco-2 cells was 71 +/- 11% (P < 0.05) when compared
      with a standard solution. CONCLUSION: Retention of folic acid fortificant during
      bread-making was substantially higher compared to retention of [6S]-5-CH(3)
      H(4)folate fortificant. Data from the TIM and Caco-2 cell trials suggest an
      inhibiting effect of the tested bread matrices on in vitro bioaccessibility of
      folates, whereas folate bioaccessibility from a breakfast meal is almost
      complete.

PMID- 20130892
TI  - Initial increased wear debris of XLPE-Al2O3 bearing in total hip arthroplasties.
AB  - INTRODUCTION: Aseptic implant loosening caused by wear debris is a common reason
      for early implant failure after total hip replacement (THR). MATERIALS AND
      METHODS: We prospectively studied 96 patients (110 hips), 48 men and 48 women
      (mean age 46.8 years, mean body mass index 26.1) who had undergone cementless THR
      (titanium stem, press-fit cup, Al(2)O(3) ball, XLPE liner) at a mean of 17.4
      months (SD 13.4). RESULTS: The semi-computerized evaluation of wear rate showed
      wear of 0.25 mm (SD 0.3) corresponding to a volume of 97.6 mm(3) (SD 121.1)
      during the first year. It was remarkable that the annual rate of wear was
      significantly lower in the second year: 0.14 mm (SD 0.1), 60.0 mm(3) (SD 78.7).
      The implant survival rate was 100%. However, two patients underwent revision
      surgery. INTERPRETATION: Good, early functionality can be achieved by a
      cementless THR including a modular stem and a XLPE-Al(2)O(3) bearing system. The
      rate of wear debris for XLPE-Al(3)O(2) was much higher than expected within the
      first year after THR. However, after the initial running-in period a significant
      decrease of wear was documented, suggesting a biphasic abrasion [0.38 mm (SD 0.2)
      within the first year vs. 0.14 mm (SD 0.1)] after the running-in-period 1 year
      following surgery.

PMID- 20130893
TI  - Metrenperone enhances collagen turnover and remodeling in the early stages of
      healing of tendon injury in rabbit.
AB  - INTRODUCTION: This study evaluated the effects of metrenperone on healing of
      unilateral, collagenase-induced lesions in the Superficial Digital Flexor Tendons
      (SDFT) of rabbits. METHODS: After controlled injury of the left SDFT, nine
      rabbits received daily treatment with metrenperone for 28 days. Another nine were
      untreated controls; in both groups the contra-lateral tendons served as uninjured
      controls. Histological and ultrastructural changes, mechanical properties, dry
      weight, collagen content, and amount of DNA in healing and control tendons were
      assessed 28 days after injury. RESULTS: Restoration of structural hierarchy was
      more organized in treated than in untreated tendons while cellularity was greater
      in the latter. At the ultrastructural level, collagen in treated lesions was
      predominantly in the form of small-diameter, new fibrils, with few large, old
      fibrils; in untreated lesions there was a high proportion of large, old fibrils
      but relatively few small, new ones. The amount of DNA in untreated injuries was
      much greater than in normal tendons, while in treated lesions it was not
      significantly different from that of uninjured controls. There were no
      significant differences in total collagen, stiffness and ultimate strength of
      injured, treated, and untreated tendons 28 days after injury. Both were
      significantly weaker than their corresponding contralaterals. CONCLUSIONS: The
      findings suggest that metrenperone had positive effects on collagen turnover,
      remodelling, and organization during acute inflammation and fibroplasia. Provided
      that the new fibrils subsequently matured in a normal manner, mechanical
      characteristics of the organized scar should be better than those of an untreated
      lesion.

PMID- 20130894
TI  - Clearance of experimental cutaneous Staphylococcus aureus infections in mice.
AB  - Staphylococcal skin infections are quite common in human patients. These
      infections often clear spontaneously, but may also progress locally and/or
      disseminate to cause serious and sometimes fatal deep infections. The present
      studies were undertaken to examine the clearance phase of experimental cutaneous
      Staphylococcus aureus infections in a mouse model system. Previous work in this
      system has shown that staphylococci applied to the skin rapidly disseminate to
      the spleen and kidney. In the present experiments the bacteria were found to
      persist at the skin infection site at a time (8 days after inoculation) when they
      had disappeared from the spleen and kidney. Examination of the infected skin at
      earlier times revealed rapid (within 6 h) invasion into the stratum corneum,
      stratum Malpighii, and dermis, but subsequent redistribution of bacteria (at 1-2
      days) to more superficial sites, particularly crusts located just above the skin
      surface. The crusts seen in these infections were of two distinct types, which
      were termed type 1 and type 2. Type 1 crusts appeared first, consisted of
      bacteria, inflammatory cells, and debris, and developed over an intact epidermis.
      Type 2 crusts arose from the process of dermal necrosis previously reported to
      take place at 2 days in this model system. In the latter situation the bacteria
      were not really cleared from the epidermis and dermis; rather those layers were
      transformed into a superficial crust that contained the bacteria. Deep hair
      follicle infections in the dermis were found in these infections, but they did
      not persist and did not seem to be a reservoir for organisms in the dermis.
      Resolution of these experimental infections appeared to involve redistribution of
      invading bacteria to more superficial locations in crusts above the skin surface,
      marked proliferation of the epidermis, loss of the bacteria-laden crusts from the
      skin, and eventual healing of the cutaneous damage.

PMID- 20130895
TI  - The association of the BLK gene with SLE was replicated in Chinese Han.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease influenced by genetic
      and environmental factors. Recently, single nucleotide polymorphisms (SNPs) in
      the region of B lymphoid tyrosine kinase (BLK) have been shown to be associated
      with SLE in Caucasian population. In this paper, we genotyped SNP rs2248932 in
      1,396 SLE patients of Chinese Han and 4,362 ethnically matched control subjects
      by using the Sequenom MassArray system. We confirmed that SNP rs2248932 in BLK
      gene was significantly associated with SLE (P = 1.41 x 10(-8) for the allele
      frequency, Odds ratio [OR] = 0.74, 95% confidence interval (CI): 0.66-0.82).The
      association of BLK in Chinese SLE patients was consistent with a dominant model
      (P = 8.88 x 10(-9), OR = 0.69, 95% CI: 0.61-0.79). In contrast to the Caucasian,
      this risk allele was the major allele in the Chinese Han; the risk allele
      frequency was higher in Chinese Han than in Caucasian. We did not find the
      association between this SNP and any subphenotype of SLE. The SNP rs2248932 was
      correlated to the expression of BLK mRNA. We conclude that the association of the
      BLK region with SLE was replicated in Chinese Han population living in mainland.

PMID- 20130896
TI  - Genetics of keloid scarring.
AB  - Keloid scarring, also known as keloid disease (KD), is a common, abnormally
      raised fibroproliferative cutaneous lesion that can occur following even minor
      skin trauma. The aetiopathogenesis of KD has remained an enigma todate compounded
      by an ill-defined clinical management. There is strong evidence suggesting a
      genetic susceptibility in individuals affected by KD, including familial
      heritability, common occurrence in twins and high prevalence in certain ethnic
      populations. This review aims to address the genetic aspects of KD that have been
      described in present literature that include inheritance patterns, linkage
      studies, case-control association studies, whole genome gene expression
      microarray studies and gene pathways that were significant in KD. In addition to
      our clinical and scientific background in KD, we used search engines, Scopus,
      Scirus and PubMed, which searched for key terms covering various genetic aspects
      of KD. Additionally, genes reported in seven whole genome gene expression
      microarray studies were separately compared in detail. Our findings indicate a
      varied inheritance pattern in KD (predominantly autosomal dominant), linkage loci
      (chromosomes 2q23 and 7p11), several human leukocyte antigen (HLA) alleles (HLA
      DRB1*15, HLA-DQA1*0104, DQ-B1*0501 and DQB1*0503), negative candidate gene case
      control association studies and at least 25 dysregulated genes reported in
      multiple microarray studies. The major pathways reportedly proposed to be
      involved in KD include apoptosis, mitogen-activated protein kinase, transforming
      growth factor-beta, interleukin-6 and plasminogen activator inhibitor-1. In
      summary, involvement of more than one gene is likely to be responsible for
      susceptibility to KD. A better understanding of the genes involved in KD may
      potentially lead to the development of more effective diagnostic, therapeutic and
      prognostic measures.

PMID- 20130897
TI  - Treatment of anti-glutamic acid decarboxylase antibody-associated limbic
      encephalitis with mycophenolate mofetil.

PMID- 20130898
TI  - Advantage of binocularity in the presence of external visual noise.
AB  - PURPOSE: External visual noise plays a major role in real life, for instance,
      when a driver tries to identify an object through a snow flurry or through a
      dirty windshield. The goal of the present investigation was to quantify, under
      such a condition, the advantage of binocular over monocular vision or, rather,
      the disadvantage of having only one eye. METHODS: Eight observers judged the
      orientation of a Landolt ring (gap always 10 arcmin), partly obscured by noise
      particles of different sizes (5, 10 or 20 arcmin). The noise particles were
      presented at a stereo disparity of 62 arcmin, i.e. beyond Panum's fusional area.
      We compared the percentage of correct responses and the reaction time between
      binocular and monocular vision. Control conditions: (1) binocular vision with
      noise particles located immediately in front of the Landolt ring (stereo
      disparity +/- 0), and (2) absence of noise particles. RESULTS: With regard to the
      percentage of correct responses, an advantage of binocular over monocular
      observation occurred only when the obscuring particles were presented at the
      stereo disparity of 62 arcmin. The advantage depended on the size of the noise
      particles. The factor was 1.24 for particles of 5 arcmin, 1.49 for 10 arcmin and
      1.59 for 20 arcmin. With regard to the reaction time, there was no difference
      between binocular and monocular vision. CONCLUSION: Binocular vision provides a
      considerable advantage over monocular vision when particles partly obstruct the
      view. This advantage is due to the capability of the visual system to construct a
      coherent percept of an object of which different parts are imaged in the right
      and left eye.

PMID- 20130899
TI  - Femtosecond lenticule extraction for the correction of myopia: preliminary 6
      month results.
AB  - PURPOSE: To report the 6-month results of a new method of refractive correction,
      femtosecond lenticule extraction (FLEx), and the preliminary outcomes in the
      first 108 eyes. METHODS: In this prospective study, a flap and a lenticule of
      intrastromal corneal tissue were cut simultaneously using a femtosecond laser.
      Thereafter, the lenticule was removed manually and the flap repositioned. One
      hundred and seven of 108 myopic eyes of 56 patients in the treatment group
      completed the final 6 months of follow-up. The patients' mean age was 35 years.
      The preoperative mean spherical equivalent (SE) was -4.59 +/- 1.3 diopters (D).
      The uncorrected visual acuity and the best spectacle-corrected visual acuity
      after 6 months, objective and manifest refractions, results of slit-lamp
      examination, the side effects, and the responses to a questionnaire are reported.
      RESULTS: Six months postoperatively, the mean SE was -0.19 +/- 0.47 D; 98.1% of
      treated eyes were within +/-1.0 D, and 74.8% of eyes within +/-0.5 D of the
      intended correction. Eight (7.4%) of 108 eyes lost one line of Snellen VA, one
      (0.9%) eye lost two Snellen lines, 46 eyes (43%) gained one line, ten eyes (9.3%)
      gained two Snellen lines, and the VA remained unchanged in 42 (39.3%) eyes. The
      patient responses to a standardized questionnaire indicated that 97.1% of
      patients were satisfied with the obtained results and would undergo the procedure
      again. CONCLUSION: FLEx appears to be a safe and promising corneal refractive
      procedure for correcting myopia.

PMID- 20130900
TI  - Successful treatment of staphylococcus-associated marginal keratitis with topical
      cyclosporine.

PMID- 20130901
TI  - Short-term variability of systemic blood pressure and submacular choroidal blood
      flow in eyes of patients with primary open-angle glaucoma.
AB  - PURPOSE: To analyse short-term variability of systemic blood pressure and
      choroidal blood flow in glaucoma patients, and compare them with ocular
      hypertensive patients and controls. SUBJECTS AND METHODS: Thirty untreated
      patients with primary open-angle glaucoma (POAG), 25 untreated patients with
      ocular hypertension (OHT) and 50 healthy controls without local therapy were
      included in the study. Continuous 5-minute measurements of arterial systemic
      blood pressure (SBP) by Finometer and choroidal blood flow (CBF) by laser Doppler
      flowmetry were obtained. Variability of SBP and CBF was analysed by means of
      coefficient of variation and analyzed in ANOVA model. Linear regression analysis
      was performed on parameters of morphological (nerve fiber layer thickness) and
      functional glaucomatous damage (visual field) on one side, and between SBP and
      CBF on the other side. RESULTS: ANOVA model demonstrated significant differences
      in variability between the groups (p = 0.003); post-hoc analysis specified a
      significantly higher short-term variability of both the blood pressure and
      choroidal blood flow in POAG patients (coefficients of variation: 3.33% +/- 1.05%
      and 3.90% +/- 2.17% respectively) than in healthy controls (coefficient of
      variation: 2.57% +/- 0.80% and 2.94% +/- 1.52% respectively). No significant
      differences were found for OHT patients. CONCLUSIONS: POAG patients without local
      therapy demonstrate an increased short-term BP and CBF variability.

PMID- 20130902
TI  - Pregnancy outcomes in female hairdressers.
AB  - PURPOSE: The hairdressing occupation may entail exposure to a wide range of
      chemical products, psychosocial and physical stress. All these factors may affect
      the health of a pregnant hairdresser and her offspring. Our aim was to analyse
      whether employment in this profession is associated with adverse reproductive
      effects. METHOD: Female hairdressers working in the 248 hairdressing salons in
      Alicante (Spain), who became pregnant for the first time after 1990 were included
      (n = 94). The incidence of spontaneous abortions, number of children born and
      their birth weight and preterm delivery among hairdressers was compared with a
      control group of shop assistants and office workers (n = 138). Information was
      collected through personal interviews at their work place. A structured
      questionnaire was used gathering information concerning exposure variables
      including the use of chemical products, ventilation at the salons, work-related
      stress and hours of standing work. In addition, socio-demographic factors and
      smoking information were obtained. Crude and adjusted relative risks (RR) and 95%
      confidence intervals (95%CI) were calculated using logbinomial regression.
      RESULTS: Hairdressers showed a non-significant increased risk of spontaneous
      abortions (RR = 1.6, 95%CI 0.9-2.7). There were no differences in preterm
      delivery and birth weight of the children born of mothers in the two groups.
      Among hairdressers, the RR of spontaneous abortion among those with high
      perceived work-related stress was 2.4 (95%CI: 0.2-28.3) relative to those with
      low or normal perceived stress. CONCLUSIONS: A slightly increased risk of
      spontaneous abortion among hairdressers was found, mainly associated with
      perceived work-related stress. Observed results deserve further research.

PMID- 20130903
TI  - Biological effect markers in exhaled breath condensate and biomonitoring in
      welders: impact of smoking and protection equipment.
AB  - PURPOSE: The objective of this study was to investigate the effect of welding as
      well as the impact of smoking and protection measures on biological effect
      markers in exhaled breath condensate. Additionally, biomonitoring of chromium,
      aluminium and nickel in urine was performed to quantify internal exposure.
      METHODS: Exhaled breath condensate (EBC) and urine samples of 45 male welders and
      24 male non-exposed control subjects were collected on Friday pre-shift and after
      8 h of work post-shift. In EBC, biological effect markers such as
      malondialdehyde, nitrite, nitrate, 3-nitrotyrosine, tyrosine, hydroxyproline,
      proline, H(2)O(2) and pH-value were measured while aluminium, nickel, and
      chromium were measured in the urine samples. RESULTS: Although internal exposure
      to aluminium, nickel and chromium in this study was low, welders showed
      significantly increased concentrations of all these parameters at baseline
      compared to non-exposed controls. Moreover, welders had higher nitrate
      concentrations in EBC at baseline and after shift. Nitrate concentration was
      considerably lower after shift if personal protection equipment was used.
      H(2)O(2) was increased only when subjects smoked during shift. CONCLUSION: It has
      been shown that welding-associated long-term and short-term health effects could
      be detected in a population of welders. The results also showed that using
      personal protection equipment is of high importance and H(2)O(2) may be an effect
      marker associated with smoking rather than with welding fumes, while nitrate in
      EBC seems to be sensitive to welding fume exposure.

PMID- 20130904
TI  - Activities of occupational physicians for occupational health services in small
      scale enterprises in Japan and in the Netherlands.
AB  - OBJECTIVES: Occupational health service (OHS) for small-scale enterprises (SSEs)
      is still limited in many countries. Both Japan and the Netherlands have universal
      OHS systems for all employees. The objective of this survey was to examine the
      activities of occupational physicians (OPs) in the two countries for SSEs and to
      investigate their proposals for the improvement of service. METHODS:
      Questionnaires on types and sizes of the industries they serve, allocation of
      service hours (current and desired), sources of information for occupational
      health activities etc. were mailed in 2006 to 461 and 335 Japanese and Dutch OPs,
      respectively, who have served in small- and medium-scale enterprises. In
      practice, 107 Japanese (23%) and 106 Dutch physicians (32%) replied,
      respectively. RESULTS AND CONCLUSIONS: Total service time per month was longer
      for OPs in the Netherlands than OPs in Japan. Japanese OPs spent more hours for
      health and safety meetings, worksite rounds, and prevention of overwork-induced
      ill health (14-16% each). Dutch OPs used much more hours for the guidance of
      absent workers (48%). Thus, service conditions were not the same for OPs in the
      two countries. Nevertheless, both groups of OPs unanimously considered that
      employers are the key persons for the improvement of OHS especially in SSEs and
      their education is important for better OHS. The conclusions should be taken as
      preliminary, however, due to study limitations including low response rates in
      both groups of physicians.

PMID- 20130905
TI  - Latest status of cadmium accumulation and its effects on kidneys, bone, and
      erythropoiesis in inhabitants of the formerly cadmium-polluted Jinzu River Basin
      in Toyama, Japan, after restoration of rice paddies.
AB  - PURPOSE: The cadmium-polluted Jinzu River Basin in Toyama, Japan, where
      nephropathy and itai-itai disease were endemic among resident farmers decades
      ago, has been almost completely restored. The aim of this study is to investigate
      whether inhabitants there would still exhibit cadmium accumulation and its
      effects on kidneys, bones, and erythropoiesis. METHODS: We performed a cross
      sectional study of 150 subjects from the polluted area and 144 controls from the
      same prefecture. Participants included female inhabitants from 34 to 74 years of
      age who underwent examinations to gather anthropometrical and medical
      information, obtain rice, blood and urine samples, and measure bone mineral
      density. RESULTS: Cadmium concentration in rice from the polluted area was lower
      than the level in the control area. Blood and urinary cadmium and urinary beta(2)
      microglobulin levels were higher in subjects from the polluted area than
      controls, and the urinary beta(2)-microglobulin was independently affected by
      urinary cadmium. Bone mineral density did not differ between the two areas, but
      it was affected by renal tubular function in subjects from the polluted area.
      Serum bone alkaline phosphatase was lower in subjects from the polluted area
      compared to controls. We detected three cases of cadmium nephropathy among the
      subjects. One of them suffered from a renal anemia type of itai-itai disease.
      CONCLUSION: Inhabitants in the formerly polluted area still had high cadmium
      accumulations and showed a characteristic natural history of chronic cadmium
      toxicity, indicating that the risk remains for developing nephropathy or itai
      itai disease in the future.

PMID- 20130906
TI  - Illness perceptions and work participation: a systematic review.
AB  - PURPOSE: Self-regulatory processes play an important role in mediating between
      the disease and the health outcomes, and potentially also work outcomes. This
      systematic review aims to explore the relationship between illness perceptions
      and work participation in patients with somatic diseases and complaints. METHODS:
      The bibliographic databases Medline, PsycINFO and Embase were searched from
      inception to March 2008. Included were cross-sectional or longitudinal studies,
      patients with somatic diseases or complaints, illness perceptions based on at
      least four dimensions of the common sense model of self-regulation, and work
      participation. RESULTS: Two longitudinal and two cross-sectional studies selected
      for this review report statistically significant findings for one or more illness
      perception dimensions in patients with various complaints and illnesses, although
      some dimensions are significant in one study but not in another. Overall, non
      working patients perceived more serious consequences, expected their illness to
      last a longer time, and reported more symptoms and more emotional responses as a
      result of their illness. Alternatively, working patients had a stronger belief in
      the controllability of their condition and a better understanding of their
      disease. CONCLUSIONS: The limited number of studies in this review suggests that
      illness perceptions play a role in the work participation of patients with
      somatic diseases or complaints, although it is not clear how strong this
      relationship is and which illness perception dimensions are most useful.
      Identifying individuals with maladaptive illness perceptions and targeting
      interventions toward changing these perceptions are promising developments in
      improving work participation.

PMID- 20130907
TI  - PIKing the right isoform: the emergent role of the p110beta subunit in breast
      cancer.
AB  - Class IA phosphoinositide-3'-kinases (PI3Ks) regulate many cellular processes.
      Despite a clear implication of PI3K in cancer, the involvement of each of its
      isoforms namely p110alpha and p110beta in the development of breast cancer
      remains elusive. Until recently, the spotlight was given to the alpha subunit;
      however, the p110beta isoform has now emerged as an interesting target as well.
      In order to determine the importance of both these subunits in breast cancer, we
      aimed to study the expression of p110alpha and p110beta in a series of invasive
      breast carcinomas. We constructed tissue microarrays from 315 invasive breast
      carcinomas and performed immunohistochemistry for p110alpha and beta, correlating
      the expression patterns with clinicopathological parameters. Furthermore, overall
      survival was analysed through Kaplan-Meier survival curves and Cox regression. We
      found that p110 subunits are expressed in 23.8% of invasive breast carcinomas, of
      which 11.8% express p110alpha and 15.2% p110beta. The p110alpha positive tumours
      correlated with hormone receptor (HR) expression, and were not associated with
      overall survival. The membrane expression of p110beta was associated with worse
      prognosis. This was due to its link to HER2-overexpression, lower age of onset,
      higher grade, lymph node involvement, distant metastasis and was inversely
      associated with HR status. Furthermore, p110beta expression was associated with
      worse overall survival. Importantly our results indicate a role for the beta
      subunit in the development/progression of HER2-overexpressing tumours,
      highlighting possible therapeutic associations between HER2 and p110beta
      inhibitors.

PMID- 20130908
TI  - Effect of misdiagnosis on the prognosis of anorectal malignant melanoma.
AB  - OBJECTIVE: Anorectal malignant melanoma (AMM) is frequently subjected to
      misdiagnosis. Here the effect of misdiagnosis on the prognosis of AMM was
      investigated. METHODS: Between 1995 and 2007, 79 patients managed for AMM were
      reviewed; 46 (58.23%) of them had been misdiagnosed during the symptoms, while 33
      (41.77%) cases had been diagnosed exactly not more than 1 week after the first
      visit. Diseases misdiagnosed were categorized as cancer, hemorrhoids, polyps and
      other diseases. Data were statistically analyzed by using the life tables and
      Kaplan-Meier curves. The software used was SPSS 16.0 for Windows. RESULTS: The 1
      , 2-, 3- and 5-year survival rates of AMM patients were 58, 33, 24 and 16%,
      respectively, and the median survival time was 14.0 months; 1-, 2-, 3- and 5-year
      survival rates of the misdiagnosed patients were 61, 22, 22 and 11%,
      respectively, and the median survival time was 14.0 months; 1-, 2-, 3- and 5-year
      survival rates of the patients not misdiagnosed were 55, 44, 25 and 25%,
      respectively, and the median survival time was 12.0 months. Analyses based on
      Kaplan-Meier curves revealed no significant effect of misdiagnosis on the
      survival of AMM patients (P > 0.05). Nevertheless, the diseases misdiagnosed
      significantly affect the prognosis (P = 0.009); AMM misdiagnosed as hemorrhoids
      had a poor prognosis, with a 1-year survival rate of only 29% and the median
      survival of only 6.0 months. CONCLUSIONS: The misdiagnosed patients had
      relatively poor prognosis, but the effect of misdiagnosis on the prognosis was
      not significant; however, misdiagnosis of AMM as hemorrhoids seriously affected
      the prognosis.

PMID- 20130909
TI  - Benefit of radiotherapy for 90 patients with resected intrahepatic
      cholangiocarcinoma and concurrent lymph node metastases.
AB  - PURPOSE: To evaluate the role of radiotherapy for patients with resected
      intrahepatic cholangiocarcinoma with concurrent macroscopic abdominal lymph node
      metastases. METHODS: We identified 90 patients with resected intrahepatic
      cholangiocarcinoma and concurrent regional lymph node metastases treated between
      1999 and 2008, thereinto 24 patients received local limited external beam
      radiotherapy (classified as the radiotherapy group) with a median total dose of
      50 Gy (range 34-60 Gy) in fractions of 2 Gy five times a week. The remaining 66
      patients did not receive external beam radiotherapy (classified as the non
      radiotherapy group). We studied survival and tumor response to radiotherapy,
      demonstrated by symptoms and results of imaging, by Kaplan-Meier method and Cox
      analysis. RESULTS: After radiotherapy, lymph nodes showed partial response in
      nine patients (37.5%) and complete response in nine patients (37.5%). Median
      survival was 19.1 months in the radiotherapy group and 9.5 months in the non
      radiotherapy group (P = 0.011). Multivariate analysis showed that increasing age,
      multiple intrahepatic primary tumors, higher level of CA19-9, and non
      radiotherapy group were related to a poorer prognosis. The most common cause of
      death was intrahepatic recurrence, and death resulting from lymph node-related
      complications was similar between the two groups. CONCLUSIONS: External beam
      radiotherapy seems to improve the prognosis of patients with resected
      intrahepatic cholangiocarcinoma and concurrent macroscopic lymph node metastases.

PMID- 20130910
TI  - Recombinant human endostatin improves anti-tumor efficacy of paclitaxel by
      normalizing tumor vasculature in Lewis lung carcinoma.
AB  - PURPOSE: Normalization of the tumor vasculature and microenvironment by several
      angiogenesis inhibitors has been reported. Given that recombinant human
      endostatin (rh-endostatin) is also an endogenous angiogenesis inhibitor, a
      comprehensive evaluation of the effects of rh-endostatin on tumor vasculature and
      microenvironment and chemotherapy sensitivity would be favorable. METHODS:
      Multiple treatment schedules of the combination of rh-endostatin and paclitaxel
      were tested in Lewis lung carcinoma. Further, we monitored microvascular density,
      tumor hypoxic fraction, and collagen covered tumor vessels at three different
      time points following the treatment of rh-endostatin, as well as the
      transcription of angiogenesis related factors (vascular endothelial growth factor
      A and thrombospondin-1) and vasculature markers (regulator of G-protein signaling
      5 and platelet/endothelial cell adhesion molecule-1). RESULTS: The anti-tumor
      efficacy of paclitaxel was significantly improved 7 days after the treatment of
      rh-endostatin. Tumor microvascular density was decreased by rh-endostatin,
      although it became even higher 7 days after termination of rh-endostatin. Non
      necrotic hypoxic fraction was significantly reduced 7 days after treatment of rh
      endostatin, accompanied with increased collagen covered tumor vessels and
      coverage of pericytes around endothelial cells. Rh-endostatin could transiently
      upregulate the transcription of thrombospondin-1 and modulate the imbalance
      between vascular endothelial growth factor-A and thrombospondin-1. CONCLUSION: Rh
      endostatin could normalize the tumor vasculature and microenvironment in Lewis
      lung carcinoma probably via modulation of the balance between vascular
      endothelial growth factor-A and thrombospondin-1. During the time of vascular
      normalization, paclitaxel treatment was found to have maximal effect on tumor
      growth delay.

PMID- 20130911
TI  - Identification of HTA as a novel-specific marker for human hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy in the
      world, especially in China. Early diagnosis of new and recurrent hepatocellular
      carcinoma, followed by timely treatment, will help decrease mortality. Currently
      biomarkers are not satisfactory. Better diagnostic methods are highly demanded.
      METHODS: In this study, we have used in silico identification and RT-PCR test and
      discovered a hepatoma associated gene (HTA). Knockdown of endogenous HTA
      expression was performed by small interfering RNA in malignant hepatocyte HepG2.
      Then we tested the cell proliferative ability of these cells in vitro and in
      vivo. RESULTS: HTA was expressed specifically in some kinds of tumors, but not
      detected in any normal tissues. It was expressed especially high in
      hepatocellular carcinoma. Knockdown of endogenous HTA expression in HepG2 by
      small interfering RNA attenuated HCC cell growth. CONCLUSIONS: HCA is a very good
      marker for tumors, especially for HCC. It could play important roles in HCC
      development and progression and can be a promising molecular target for the
      development of new diagnostic and therapeutic strategies for HCC.

PMID- 20130912
TI  - Analysis of related factors associated with radiation pneumonitis in patients
      with locally advanced non-small-cell lung cancer treated with three-dimensional
      conformal radiotherapy.
AB  - PURPOSE: To investigate the correlation among DVH (lung dose-volume histogram)
      parameters, clinical factors, and grade > or = 2 radiation pneumonitis (RP) in
      patients with locally advanced non-small-cell lung cancer (NSCLC) treated with
      three-dimensional conformal radiotherapy (3D-CRT), and the differences between
      patients treated with 3D-CRT alone or that combined with chemotherapy on RP.
      PATIENTS AND METHODS: As much as 93 patients of stage III NSCLC were treated with
      3D-CRT, among which 36 were treated with chemotherapy after 3D-CRT, 57 received
      3D-CRT treatment alone. The radiation dose was 62.5-65 Gy (BED = 68-72.7 Gy).
      RESULTS: The morbidity of grade > or = 2 RP was 49.5%, of which grade 2 and grade
      3 were 33.3 and 16.1%, respectively. The morbidity of RP in those patients
      treated with chemotherapy after radiotherapy was evidently higher than that of
      patients treated with radiotherapy alone (61.1 vs. 42.1%). According to the
      single factor analysis, V5-V50 and MLD of both the ipsilateral and the whole lung
      were all related to the occurrence of RP; comparing grade 3 with grade 2 within
      the same group, except V45, V50, TV20, TV30, and TMLD, other parameters also had
      their statistical significance (P < 0.01); comparing the non-chemotherapy-treated
      group with the chemotherapy-treated group, TV30 and TV35 had their statistical
      significance. According to logistic regression analysis; the occurrence of RP was
      evidently associated with the comprehensive value of DVH parameters,
      chemotherapy, and gender. Chemotherapy has increased the risk of RP 7.6 times.
      The increase of each score in the comprehensive value of DVH parameters would
      increase the risk of RP 22.7 times. CONCLUSION: The comprehensive values of DVH
      parameters, chemotherapy, and gender have independent effects on the occurrence
      of RP. Most of DVH parameters were associated with the occurrence of RP. The
      curve shape composed of multiple points in DVH parameters was more important than
      any single DVH parameter.

PMID- 20130913
TI  - Serum protein biomarkers screening in HCC patients with liver cirrhosis by ICAT
      LC-MS/MS.
AB  - BACKGROUND: The prognosis of HCC remains poor mainly because of the lack of
      diagnosis biomarkers especially in patients with cirrhosis background. METHODS:
      To identify serum biomarkers for HCC, we use cleavable stable isotope labeling
      (cICAT) combined with LC-electrospray ionization tandem mass spectrometry (LC-ESI
      MS/MS) to compare the serum proteome between liver cirrhosis and HCC patients.
      Sera from nine liver cirrhosis patients and nine HCC patients were selected for
      screening study. Then the alpha-1-acid glycoprotein (AGP) was chosen for
      validation by western blot. AGP was measured in the separate validation study
      including 52 HCC patients and 40 liver cirrhosis patients by rate nephelometry.
      Its value for HCC diagnosis from liver cirrhosis was also appreciated through
      receiver operating curve (ROC). RESULTS: We quantified and identified 31
      different proteins which include AGP, complement C4, haptoglobin, alpha-1
      antitrypsin precursor, alpha-2-macroglobulin precursor, prothrombin precursor and
      ubiquitin carboxyl-terminal hydrolase 44 (USP44), etc. The serum concentration of
      AGP in HCC patients (n = 52) was significantly higher than in liver cirrhosis (n
      = 40) (P < 0.005) in validation study. AGP was useful for discrimination of the
      HCC cases from LC patients when the AFP levels were below 500 ng/ml. The area
      under curve (AUC) of the AGP and the combination of AGP and AFP were 0.834 (P <
      0.0005, 95% CI: 0.734-0.934) and 0.880 (P < 0.0005, 95% CI, 0.789-0.970)
      separately, which are higher than AFP alone (0.538, P = 0.604, 95% CI: 0.386
      0.689). CONCLUSION: cICAT combined with LC-MS/MS-based serum proteome analysis
      can be useful in the screening of serum biomarkers for HCC. Alpha-1-acid
      glycoprotein combining AFP could aid the diagnosis of HCC.

PMID- 20130914
TI  - Experiments to produce cysts in cultures of Histomonas meleagridis--the agent of
      histomonosis in poultry.
AB  - Experiments were done with cultured trophozoite stages of different clonal
      strains (Histomonas meleagridis/Turkey/Austria/2922-C6/04 and H.
      meleagridis/Chicken/Hungary/5009-C2/05) of H. meleagridis in order to induce a
      cyst formation as it is known in other intestinal parasites. It was shown that
      the best multiplication of H. meleagridis occurred at 40 degrees C in a full
      medium 199, when fetal calf serum and rice starch had been added. Under these
      conditions, numerous amoebic stages (8-12 microm in diameter) without and a few
      with flagellum were seen showing regular reproduction rates. When the conditions
      of culture were experimentally changed-and thus became worse-by decreasing the
      temperature, by deprivation of the medium from fetal calf serum and/or rice
      starch, and by changing the osmolarity, the pH, or the MgCl(2) concentration,
      many of the amoebic stages (containing starch granules) were destroyed, and
      several had obtained a spherical shape. If the culture conditions became even
      worse, smaller spherical stages occurred, which had only diameters of 4-7 microm
      and which appeared more condensed. Both spherical stages did not contain starch
      granules. All the previously seen stages disappeared constantly. Since a similar
      decrease of the optimal living conditions also occurs when intestinal or cloacal
      feces are deposited outside from the bird's body, the results obtained here may
      underline the interpretation that some of the formerly amoebic stages are able to
      become large spherical stages and later small spherical stages. The large
      spherical stage would be some type of precysts while the smaller ones would
      represent true cysts.

PMID- 20130915
TI  - Novel mutations in the connexin43 (GJA1) and GJA1 pseudogene may contribute to
      nonsyndromic hearing loss.
AB  - Connexins (CXs), a large family of membrane proteins, are key components of gap
      junction channels. Among a cohort of patients with nonsyndromic hearing loss, we
      have recently identified three novel missense mutations in the GJA1 gene and GJA1
      pseudogene (rhoGJA1) as likely being causally related to hearing loss. However,
      the functional alteration of CX43 caused by the mutations of GJA1 and rhoGJA1
      gene remains unclear. This study compares the intracellular distribution and
      assembly of three CX43 mutants expressed in HeLa cells with their wild-type (WT)
      counterparts and the effects of the mutant proteins on those cells. Localization
      assay of WT CX43 reveals a typical punctuate fluorescence pattern of a gap
      junction channel between neighboring expression cells. Additionally,
      immunoblotting analysis of the transfectants confirms the production of mutant
      proteins, in which their distributions along appositional membranes are
      determined using immunofluorescent staining procedures. Furthermore, dye transfer
      assay results demonstrate that gap junctional intercellular communication is less
      in HeLa cells carrying mutant GJA1 or rhoGJA1 gene than in WT-expressing cells.
      The results of this study suggest that the three mutations in GJA1 or rhoGJA1
      that we previously reported result in at least partial loss of normal functions
      carried out by CX43, which may form a basis for the mechanism contributing to
      hearing loss in patients.

PMID- 20130916
TI  - You can't run but you can hide: refuge use in frog tadpoles elicits density
      dependent predation by dragonfly larvae.
AB  - The potential role of prey refuges in stabilizing predator-prey interactions is
      of longstanding interest to ecologists, but mechanisms underlying a sigmoidal
      predator functional response remain to be fully elucidated. Authors have
      disagreed on whether the stabilizing effect of prey refuges is driven by prey-
      versus predator-centric mechanisms, but to date few studies have married predator
      and prey behavioural observations to distinguish between these possibilities. We
      used a dragonfly nymph-tadpole system to study the effect of a structural refuge
      (leaf litter) on the predator's functional response, and paired this with
      behavioural observations of both predator and prey. Our study confirmed that
      hyperbolic (type II) functional responses were characteristic of foraging
      predators when structural cover was low or absent, whereas the functional
      response was sigmoidal (type III) when prey were provided with sufficient refuge.
      Prey activity and refuge use were density independent across cover treatments,
      thereby eliminating a prey-centric mechanism as being the genesis for density
      dependent predation. In contrast, the predator's pursuit length, capture success,
      and handling time were altered by the amount of structure implying that observed
      shifts in density-dependent predation likely were related to predator hunting
      efficiency. Our study advances current theory by revealing that despite fixed
      proportion refuge use by prey, presence of a prey refuge can induce density
      dependent predation through its effect on predator hunting strategy. Ultimately,
      responses of predator foraging decisions in response to changes in prey
      availability and search efficiency may be more important in producing density
      dependent predation than the form of prey refuge use.

PMID- 20130917
TI  - Branchio-oto-renal syndrome caused by partial EYA1 deletion due to LINE-1
      insertion.
AB  - A 7-year-old Japanese girl with conductive deafness and preauricular fistulae
      developed proteinuria. She had renal insufficiency, and ultrasound revealed
      bilateral small kidneys. These findings indicated that she had branchio-oto-renal
      (BOR) syndrome. In the present patient, we identified, by using multiplex
      ligation-dependent probe amplification (MLPA) analysis, a heterozygous EYA1 gene
      deletion comprising at least exons 5 to 7. In her parents, we did not detect any
      deletion in EYA1 by MLPA, so the deletion was a de novo mutation. PCR analysis
      and sequencing of patient DNA revealed a heterozygous approximately 17 kb EYA1
      deletion starting from the eight last bases of exon 4 and proceeding to base
      1,217 of intron 7. Furthermore, in place of this deleted region was inserted a
      3756-bp-long interspersed nuclear elements-1 (LINE-1, L1). Accordingly, RT-PCR
      showed that exons 4-7 were not present in EYA1 mRNA expressed from the mutated
      allele. Although there are reports of L1 element insertion occurring in various
      human diseases, this is the first report of a large EYA1 deletion in combination
      with L1 element insertion.

PMID- 20130918
TI  - Calcinosis cutis universalis with pediatric systemic lupus erythematosus.

PMID- 20130919
TI  - A comparative proteomic study of nephrogenesis in intrauterine growth
      restriction.
AB  - Nephrogenesis requires a fine balance of many factors that can be disturbed by
      intrauterine growth restriction (IUGR), leading to a low nephron endowment. The
      aim of this study was to test the hypothesis that IUGR affects expression of key
      proteins that regulate nephrogenesis, by a comparative proteomic approach. IUGR
      was induced in Sprague-Dawley (SD) rats by isocaloric protein restriction in
      pregnant dams. A series of methods, including two-dimensional gel electrophoresis
      (2-DE), silver staining, mass spectrometry and database searching was used. After
      silver staining, 2-DE image analysis detected an average 730 + or - 58 spots in
      the IUGR group and 711 + or - 73 spots in the control group. The average matched
      rate was 86% and 81%, respectively. The differential proteomic expression
      analysis found that 11 protein spots were expressed only in the IUGR group and
      one in the control group. Seven protein spots were up-regulated more than
      fivefold and two were down-regulated more than fivefold in the IUGR group
      compared with those in control group. These 21 protein spots were preliminarily
      identified and were structural molecules, including vimentin, perlecan, gamma
      actin and cytokeratin 10, transcription regulators, transporter proteins,
      enzymes, and so on. These proteins were involved primarily in energy metabolism,
      oxidation and reduction, signal transduction, cell proliferation and apoptosis.
      Data from this study may provide, at least partly, evidence that abnormality of
      metabolism, imbalance of redox and apoptosis, and disorder of cellular signal and
      cell proliferation may be the major mechanisms responsible for abnormal
      nephrogenesis in IUGR.

PMID- 20130920
TI  - The evolving place of incretin-based therapies in type 2 diabetes.
AB  - Treatment options for type 2 diabetes based on the action of the incretin hormone
      glucagon-like peptide-1 (GLP-1) were first introduced in 2005. These comprise the
      injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor on the one
      hand and orally active dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) raising
      endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP
      4. In adult medicine, both treatment options are attractive and more commonly
      used because of their action and safety profile. The incretin-based therapies
      stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent
      manner and carry no intrinsic risk of hypoglycaemia. GLP-1 receptor agonists
      allow weight loss, whereas DPP-4 inhibitors are weight neutral. This review gives
      an overview of the mechanism of action and the substances and clinical data
      available.

PMID- 20130921
TI  - Mutant-type alpha5(IV) collagen in a mild form of Alport syndrome has residual
      ability to form a heterotrimer.
AB  - Alport syndrome (AS) is caused by mutations in type IV collagen alpha3, alpha4,
      and alpha5 chains. The three chains form a heterotrimer. We have previously shown
      that all 15 types of recombinant alpha5(IV) chains with mutations, corresponding
      to AS mutations, in the noncollagenous (NC1) domain are defective in terms of
      heterotrimer formation and/or secretion of the heterotrimer from cells. A
      relatively large family with Cys1638Tyr in the NC1 domain of the alpha5(IV) chain
      has been found to have mild AS phenotypes without hearing loss or ocular
      abnormalities. Renal biopsies of different family members also revealed the
      presence of the alpha3(IV), alpha4(IV), and alpha5(IV) chains in the glomerular
      basement membrane. In our study, we introduced the mutation corresponding to
      Cys1638Tyr into the alpha5(IV) chain and characterized the mutant chain. In cells
      containing the mutant-type alpha5(IV) chain, heterotrimer formation in the cells
      and secretion of the alpha5(IV) chain in the monomeric form from the cells were
      markedly decreased compared with cells containing the wild-type chain. However,
      the heterotrimer that was formed from the mutant chain was still able to be
      secreted from the cells. The residual ability of the mutant chain may have led to
      the unique phenotypes found in the AS family with the Cys1638Tyr mutation.

PMID- 20130922
TI  - Enzymatic disease of the podocyte.
AB  - Proteinuria is an early sign of kidney disease and has gained increasing
      attention over the past decade because of its close association with cardio
      vascular and renal morbidity and mortality. Podocytes have emerged as the cell
      type that is critical in maintaining proper functioning of the kidney filter. A
      few genes have been identified that explain genetic glomerular failure and recent
      insights shed light on the pathogenesis of acquired proteinuric diseases. This
      review highlights the unique role of the cysteine protease cathepsin L as a
      regulatory rather than a digestive protease and its action on podocyte structure
      and function. We provide arguments why many glomerular diseases can be regarded
      as podocyte enzymatic disorders.

PMID- 20130923
TI  - Toll-like receptors 2 and 4 in renal ischemia/reperfusion injury.
AB  - Toll-like receptors (TLRs) are an evolutionarily conserved family of cell
      membrane receptors that are part of the innate immunity system playing an
      important role as a first response to tissue injury. TLR2 and TLR4 are
      constitutively expressed on renal epithelium, and their expression is enhanced
      following renal ischemia/reperfusion (I/R) injury. Genetic deletion of either
      TLR2 or TLR4 protects from renal I/R injury. However, it is not known whether
      deletion of both combined protects the kidney more than a deletion of either one
      alone. Therefore, we performed renal I/R injury in mice lacking TLR2, TLR4, and
      TLR2/4, respectively. Our results demonstrate that there are no significant
      differences regarding protection from renal I/R injury in TLR2/4((-/-)) compared
      with either TLR2((-/-)) or TLR4((-/-)) gene-targeted mice as determined by
      histological evaluation and renal functional parameters. Furthermore, there was
      no difference in the number of apoptotic tubular cells and in nuclear
      translocation of nuclear factor kappa-B (NF-kappaB) between the TLR-gene-targeted
      groups. In parallel, in vitro experiments did not demonstrate an additional
      effect of the double genetic deletion compared with the single gene deletion with
      respect to tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 production in
      hypoxic isolated proximal tubular epithelial cells of the respective animals. In
      conclusion, a double genetic deletion of TLR2 and TLR4 confers a similar
      protection following renal I/R injury compared with single deletions of TLR2 and
      TLR4.

PMID- 20130924
TI  - Pediatric urolithiasis: the current surgical management.
AB  - Children represent about 1% of all patients with urolithiasis, but 100% of these
      children are considered high risk for recurrent stone formation, and it is
      crucial for them to receive a therapy that will render them stone free. In
      addition, a metabolic workup is necessary to ensure a tailored metaphylaxis to
      prevent or delay recurrence. The appropriate therapy depends on localization,
      size, and composition of the calculus, as well as on the anatomy of the urinary
      tract. In specialized centers, the whole range of extracorporeal shock-wave
      lithotripsy (ESWL), ureterorenoscopy (URS), and percutaneous nephrolithotomy
      (PCNL) are available for children, with the same efficiency and safety as in
      adults.

PMID- 20130926
TI  - Cervical laminoplasty.

PMID- 20130927
TI  - Bucks fusion.

PMID- 20130928
TI  - Cervical disc replacement C5-6.

PMID- 20130929
TI  - Occipitocervical fusion.

PMID- 20130930
TI  - Reduction of high grade listhesis.

PMID- 20130931
TI  - Autonomic dysreflexia associated with Charcot spine following spinal cord injury:
      a case report and literature review.
AB  - We report the case of a 50-year-old man presenting symptoms of autonomic
      dysreflexia associated with Charcot spine following complete C8 spinal cord
      injury. After posterior lumbar interbody fusion of L2/3 with simultaneous
      posterior instrumentation from L1 to L5, the patient recovered from the symptoms
      of autonomic dysreflexia. Although the patient began to faint when he sat up and
      transferred after surgery, it began to be resolved by continuous urinary
      catheterization, setting a limit to activity and prescription of alpha-, beta
      stimulants. Within a few weeks after performing these treatment strategies, he
      could return to active wheelchair life, and no recurrence of any symptoms was
      noted at the 6-year follow-up. Although there are only a small number of cases
      with Charcot spine presenting autonomic dysreflexia, surgical stabilization of
      the affected lesion for patients with this condition should be recommended.

PMID- 20130932
TI  - A study of the test-retest reliability of the self-perceived general recovery and
      self-perceived change in neck pain questions in patients with recent whiplash
      associated disorders.
AB  - The objectives of this study were to determine the test-retest reliability of two
      self-perceived recovery questions in patients with recent whiplash-associated
      disorders (WAD), and to assess whether remembering previous answers influences
      reliability. The self-perceived general recovery and self-perceived change in
      neck pain questions were administered to 46 patients with recent WAD 6 weeks
      after recruitment and again 3-5 days later. At follow-up, we also asked
      participants if they remembered their previous answers. We used the intra-class
      correlation coefficients (ICC) to measure the reliability of the original ordinal
      response structure and kappa statistics for dichotomized responses. The ICC [95%
      confidence intervals (CI)] for the general recovery and for the change in neck
      pain questions were 0.70 (0.60-0.80) and 0.80 (0.72-0.87), respectively. The
      kappa statistic (95% CI) for the general recovery question was 0.81 (0.64-0.99)
      when recovery was defined as "completely better" or "much improved". The kappa
      statistic (95% CI) for the change in neck pain question was 0.80 (0.62-0.99) when
      recovery was defined as "very much better" or "better". Our analysis suggests
      that the test-retest reliability may be higher for participants who remembered
      their previous responses. In conclusion, our results suggest that self-perceived
      recovery questions have adequate reliability for use in epidemiological research
      of WAD.

PMID- 20130933
TI  - Conversion to hypertrophic vertebral pseudarthrosis following percutaneous
      vertebroplasty.
AB  - To determine the role of percutaneous vertebroplasty (PVP) in bone formation and
      the union of vertebral pseudarthrosis, we analyzed 14 patients with an average
      follow-up duration of 21 months. Evaluation methods included back pain (visual
      analog scale: VAS), wedge angle, dynamic mobility, radiographic remodeling
      including callus and spur formation, and union status. The Student's t test was
      used for statistical analysis and a probability of less than 0.05 was determined
      as a significant difference. Back pain improved in all 14 patients with a VAS
      score of 57.8 +/- 23.5 mm (average +/- standard deviation) preoperatively and
      14.7 +/- 16.4 mm at the final follow-up (P < 0.001). The wedge angle decreased
      from 21.6 degrees +/- 8.3 degrees (average +/- standard deviation) preoperatively
      to 13.2 degrees +/- 6.9 degrees at the final follow-up (P < 0.001). Callus
      formation was seen in four patients. Bony spurs were seen in the affected
      vertebra in preoperative radiographs in all patients, and were further developed
      to a solidified form during follow up after PVP. Dynamic mobility of the affected
      vertebrae was 6.9 +/- 2.9 mm preoperatively, which decreased to 1.1 degrees +/-
      0.7 degrees at the final follow-up (P < 0.001). Notably, all patients showed the
      dynamic vertebral mobility of 2 mm or less. Nevertheless, only two patients
      exhibited the dynamic vertebral mobility of 0 mm at the final follow-up, which is
      referred to as bone union. These findings indicate that PVP serves as a
      mechanical stabilizer for vertebral pseudarthrosis, which leads to immediate pain
      relief and segmental bony responses.

PMID- 20130934
TI  - Segment-by-segment stabilization for degenerative disc disease: a hybrid
      technique.
AB  - Patients with multisegmental degenerative disc disease (DDD) resistant to
      conservative therapy are typically treated with either fusion or non-fusion
      surgical techniques. The two techniques can be applied at adjacent levels using
      Dynesys (Zimmer GmbH, Winterthur, Switzerland) implants in a segment-by-segment
      treatment of multiple level DDD. The objective of this study was to evaluate the
      clinical and radiological outcome of patients treated using this segment-by
      segment application of Dynesys in some levels as a non-fusion device and in other
      segments in combination with a PLIF as a fusion device. A consecutive case series
      is reported. The sample included 16 females and 15 males with a mean age of 53.6
      years (range 26.3-76.4 years). Mean follow-up time was 39 months (range 24-90
      months). Preoperative Oswestry disability index (ODI), back- and leg-pain scores
      (VAS) were compared to postoperative status. Fusion success and system failure
      were assessed by an independent reviewer who analyzed AP and lateral X-rays. Back
      pain improved from 7.3 +/- 1.7 to 3.4 +/- 2.7 (p < 0.000002), leg pain from 6.0
      +/- 2.9 to 2.3 +/- 2.9 (p < 0.00006), and ODI from 51.6 +/- 13.2% to 28.7 +/-
      18.0% (p < 0.00001). Screw loosening occurred in one of a total of 222 implanted
      screws (0.45%). The results indicate that segment-by-segment treatment with
      Dynesys in combination with interbody fusion is technically feasible, safe, and
      effective for the surgical treatment of multilevel DDD.

PMID- 20130935
TI  - Bioceramic vertebral augmentation with a calcium sulphate/hydroxyapatite
      composite (Cerament SpineSupport): in vertebral compression fractures due to
      osteoporosis.
AB  - A prospective, non-randomized multicenter study was initiated to study efficacy
      and safety of a partly resorbable composite of calcium sulphate and
      hydroxyapatite (Cerament SpineSupport), a novel, injectable bioceramic, in
      osteoporotic patients with vertebral compression fractures during 18-month follow
      up. Fifteen patients with low-energy trauma and 1-2 vertebral compression
      fractures verified by magnetic resonance imaging were recruited to undergo
      percutaneous bioceramic vertebral augmentation under fluoroscopy. The patients
      were treated with a highly flowable bioceramic containing calcium sulphate,
      hydroxyapatite and the non-ionic radiocontrast agent iohexol, with final setting
      time within 1 h. After the procedure, the patients were allowed to mobilize after
      2 h. Pain (VAS), occurrence of remote and adjacent fractures, and Quality of Life
      (QoL; SF-36 and EQ-5D) was recorded during 18 months. The injected volume of the
      composite material ranged from 2.8 to 9 mL (mean 4.2 mL). Pre-operative VAS score
      was mean 70.3 (CI95% +/-8.7) with an immediate post-operative pain relief, which
      was maintained at the 4-week visit (mean 26.4 with CI95% +/-16.1) and 8-week
      visit (mean 18.0 with CI95% +/-13.5 pain relief). Eighty percent of the patients
      demonstrated a clinical improvement. The pain relief was maintained over 18
      months and no adjacent fractures were observed. There was a statistically
      significant improvement of physical components in the QoL assessment. No extra
      vertebral leakage or neurological deficits were reported in this series. This
      first prospective multicenter study on a partly resorbable bioceramic material
      indicate that fracture healing can be achieved with sustained pain relief over a
      follow-up period of 18 months in an osteoporotic patient population with
      vertebral compression fractures.

PMID- 20130936
TI  - The development of a sleep apnea screening program in Romanian type 2 diabetic
      patients: a pilot study.
AB  - To determine the feasibility of a sleep apnea screening program in Romanian
      patients with type 2 diabetes and obesity attending outpatient clinic of a
      diabetes center (the standard for routine care in Romania). The Epworth
      Sleepiness Scale was administered to 80 consecutive patients with type 2 diabetes
      and a body mass index (BMI) >=30 kg/m2. Patients with a score >10 at this scale
      were referred to polysomnography for a sleep study. Overall, 20% of these
      patients had excessive daytime sleepiness (Epworth Sleepiness Scale >10), and in
      all of these cases, obstructive sleep apnea was confirmed. Of these patients,
      33.3% had moderate OSA (AHI = 15-30 events/h of sleep), and 58.3% had severe OSA
      (AHI >=30 events/h of sleep). Individuals with OSA were more frequent males, have
      higher BMI, higher waist circumference, and lower HDL-cholesterol compared with
      non-apneic subjects. Hb A1c, diabetes duration, and age were not statistically
      different between the two groups. OSA odds increased 1.1 times with every 1-cm
      increase in abdominal circumference (95%CI: 1.01-1.13) and 1.2 times with every
      kg/m2 increase in BMI (95%CI: 1.05-1.38). These associations remained
      statistically significant even after adjustment for age and sex. The prevalence
      of OSA in the sampled population was high. These findings suggest the need for
      more data regarding prevalence of obstructive sleep apnea in Romanian patients
      with type 2 diabetes. Furthermore, associations found may form a basis to develop
      specific recommendations for screening of sleep apnea in patients with type 2
      diabetes from Romania.

PMID- 20130937
TI  - Insulin resistance is independently associated with peripheral and autonomic
      neuropathy in Korean type 2 diabetic patients.
AB  - In addition to chronic hyperglycemia, insulin resistance itself has been proposed
      to cause a diabetic neuropathy. We evaluated the role of insulin resistance in
      the pathogenesis of peripheral and autonomic neuropathy in patients with type 2
      diabetes. Eighty-six patients with type 2 diabetes were evaluated for the
      anthropometric and biochemical profiles, and Kitt value was calculated from
      insulin tolerance test to assess the insulin resistance. Various autonomic
      function tests, nerve conduction velocity, and quantitative sensory tests were
      performed to assess autonomic and peripheral neuropathy. In univariate analysis,
      both autonomic and peripheral neuropathy were significantly associated with
      glycemic exposure index (GE index), HDL-cholesterol, duration of DM, and Kitt
      value. In stepwise linear regression analysis, GE index was an independent
      predictor of autonomic and peripheral neuropathy (beta = 0.643, P < 0.001; beta =
      0.207, P = 0.013, respectively), and Kitt value was also an independent factor
      for the autonomic and peripheral neuropathy (beta = - 0.306, P < 0.001; beta = -
      0.329, P < 0.001, respectively). Low HDL-cholesterol increased the odds ratio for
      peripheral neuropathy. Insulin resistance is independently associated with
      peripheral and autonomic neuropathy in Korean Type 2 diabetic patients along with
      hyperglycemia and HDL-cholesterol.

PMID- 20130938
TI  - Identification and characterization of a novel capsid protein encoded by
      Singapore grouper iridovirus ORF038L.
AB  - Singapore grouper iridovirus (SGIV) is an important pathogen isolated from
      grouper, Epinephelus tauvina, and characterized as a novel ranavirus. To better
      understand the function of viral structural genes involved in SGIV infection and
      virus-host interactions, a candidate gene, VP38 (ORF038L), was investigated in
      this study. SGIV VP38 was found to encode a 170-aa peptide containing an RGD
      motif, and it showed significant identity only to members of the genus
      Iridovirus, family Iridoviridae, except megalocytivirus. The VP38 gene was
      identified by temporal expression pattern analysis and drug inhibition assay as a
      late (L) gene. Immunofluorescence localization revealed that P38 was distributed
      predominately in the cytoplasm and that association of VP38 with viral factories
      increased at the late stage of SGIV infection. Consistent results from
      immunoelectron microscopy (IEM) and western blot analysis revealed that SGIV VP38
      is a viral capsid protein. Furthermore, antibodies specific for SGIV VP38
      exhibited substantial SGIV-neutralizing activity in vitro, suggesting that VP38
      might play an important role in SGIV infectivity.

PMID- 20130939
TI  - Microwave-assisted reaction of glycosylamine with aspartic acid.
AB  - The synthesis of N-protected glycosyl amino acids from amines has been
      investigated and it was found that, under microwave conditions, glycosylamines
      could be hydrolyzed leading to new products containing a glycosyl ester linkage.
      The efficiency of the microwave-induced glycosylation of aspartic acid was
      studied comparing the microwave activity between amide and ester bond formation.
      Different sugar moieties have been employed to demonstrate the simple and
      reproducible coupling methodology. New glycosyl ester compounds were further
      characterized by NMR spectroscopy.

PMID- 20130940
TI  - Mesh plug and Lichtenstein patch repairs at 12 months follow-up: no differences
      in outcome.

PMID- 20130941
TI  - A method for the reduction of chronic pain after tension-free repair of inguinal
      hernia: iliohypogastric neurectomy and subcutaneous transposition of the
      spermatic cord.

PMID- 20130942
TI  - Late mesh migration through the stomach wall after laparoscopic refundoplication
      using a dual-sided PTFE/ePTFE mesh.
AB  - We report a rare complication after laparoscopic fundoplication using a dual
      sided PTFE/ePTFE (Bard(r) CrurasoftTM) mesh fixation. A 53-year-old man was re
      operated for a recurrent hiatal hernia. The hiatal hernia was reinforced using a
      mesh. Two years later, the patient presented with serious dysphagia and weight
      loss. An endoscopy revealed a migrated mesh in the stomach. The mesh was excreted
      within the stool without notice. The PTFE/ePTFE mesh, which is designed for
      treating hiatal defects, is considered to have superior tissue incorporation,
      together with less adhesion formation and fistulation. As mesh migration into the
      upper gastrointestinal tract is possible, it should be used with great care in
      the peri-oesophageal region.

PMID- 20130943
TI  - Successful treatment with tacrolimus of progressive interstitial pneumonia
      associated with amyopathic dermatomyositis refractory to cyclosporine.
AB  - A 58-year-old male was admitted to our hospital because of periungual nailfold an
      erythema and erythematous rash on the dorsal joints of his hands and feet, but no
      muscle weakness. He was thus diagnosed to have amyopathic dermatomyositis. He had
      moderate hypoxemia and his chest computed tomography scans demonstrated bilateral
      ground-glass opacities, implicating complication with interstitial pneumonia.
      Therapy was initiated with pulsed methylprednisolone followed by high-dose
      corticosteroids, pulsed cyclophosphamide, and cyclosporine. The skin
      manifestations improved; however, the pulmonary infiltrates and hypoxemia
      deteriorated during the 2-month period of the treatment. The treatment was
      switched from cyclosporine to tacrolimus because of an inadequate clinical
      response to the therapy, and this resulted in the resolution of interstitial
      pneumonia. This case indicates that tacrolimus administration should be
      considered for patients with this life-threatening disorder when it is judged to
      be refractory to cyclosporine.

PMID- 20130944
TI  - Tits use amodal completion in predator recognition: a field experiment.
AB  - Amodal completion enables an animal to perceive partly concealed objects as an
      entirety, and to interact with them appropriately. Several studies, based upon
      either operant conditioning or filial imprinting techniques, have shown that
      various animals (both mammals and birds) can perform amodal completion. Before
      this study, the use of amodal completion by untrained animals in the recognition
      of objects had not been considered. Using two feeders, we observed in a field
      experiment the reaction of tits to the torso of a sparrowhawk (partly occluded or
      an 'amputated' dummy) in two different treatments (sparrowhawk torso vs. complete
      dummy pigeon; and torso vs. complete dummy sparrowhawk). It is clear that the
      birds considered the two torso variants as predators and kept away from both of
      them when the second feeder offered a 'pigeon' instead. On the other hand, when a
      'complete sparrowhawk' was present on the second feeder, the number of visits to
      the occluded torso remained low; while the number of visits to the amputated one
      increased threefold. Birds risked perching near what was clearly an amputated
      torso; while the fear of a "hiding" (occluded) torso remained unchanged, when the
      second feeder did not provide a safe alternative. Such discrimination between
      torsos requires the ability for amodal completion. Our results demonstrate that
      in their recognition process, the birds not only use simple sign stimuli, but
      also complex cognitive functions.

PMID- 20130945
TI  - Rational maximizing by humans (Homo sapiens) in an ultimatum game.
AB  - In the human mini-ultimatum game, a proposer splits a sum of money with a
      responder. If the responder accepts, both are paid. If not, neither is paid.
      Typically, responders reject inequitable distributions, favoring punishing over
      maximizing. In Jensen et al.'s (Science 318:107-109, 2007) adaptation with apes,
      a proposer selects between two distributions of raisins. Despite inequitable
      offers, responders often accept, thereby maximizing. The rejection response
      differs between the human and ape versions of this game. For humans, rejection is
      instantaneous; for apes, it requires 1 min of inaction. We replicate Jensen et
      al.'s procedure in humans with money. When waiting 1 min to reject, humans favor
      punishing over maximizing; however, when rejection requires 5 min of inaction,
      humans, like apes, maximize. If species differences in time horizons are
      accommodated, Jensen et al.'s ape data are reproducible in humans.

PMID- 20130946
TI  - Donor payoffs and other-regarding preferences in cotton-top tamarins (Saguinus
      oedipus).
AB  - Helping others at no cost to oneself is a simple way to demonstrate other
      regarding preferences. Yet, primates exhibit mixed results for other-regarding
      preferences: chimpanzees and tamarins do not show these effects, whereas capuchin
      monkeys and marmosets preferentially give food to others. One factor of relevance
      to this no-cost food donation is the payoff to the donor. Though donors always
      receive the same payoffs regardless of their choice, previous work varies in
      whether they receive either a food reward or no food reward. Here, I tested
      cotton-top tamarins in a preferential giving task. Subjects could choose from two
      tools, one of which delivered food to a partner in an adjacent cage and the other
      of which delivered food to an empty cage. Thus, subjects could preferentially
      give or withhold food from a partner. I varied whether subjects received food
      payoffs, whether a partner was present or absent, and whether the partner was a
      non-cagemate or the subject's mate. Results showed that the subjects' overall
      motivation to pull either tool declined when they did not receive any food.
      Additionally, they did not preferentially donate or withhold food, regardless of
      their own payoff or their relationship with the partner. Thus, cotton-top
      tamarins do not take advantage of cost-free food giving, either when they might
      gain in the future (mates) or when they have no opportunity for future
      interactions (non-cagemates).

PMID- 20130948
TI  - Three-quadrant mucosal excision for solitary rectal ulcer syndrome.

PMID- 20130947
TI  - Integrated gene networks in breast cancer development.
AB  - Breast cancer is a complex and heterogenous disease. Classical molecular medical
      approaches cannot fully understand and comprehend its pathogenesis. In this
      review, the development of new biological markers for the early detection and
      creation of guided and specific therapy of breast cancer are discussed in light
      of the rapid advances in the "omics". Results of cancer research in combination
      with large-scale methods that examine the expression status of genes and proteins
      have identified a large number of new biomarkers as well as confirmed the human
      growth hormone as an important player in the pathogenesis of this disease through
      its autocrine regulation where it influences the activation of Pax5 and HOXA1
      gene networks.

PMID- 20130949
TI  - Suture clutter can be prevented by a simple method in delayed anastomosis during
      the Turnbull-Cutait operation.

PMID- 20130950
TI  - En bloc resection for malignant colouterine fistula.
AB  - Colouterine fistula is a rare clinical entity. A literature search revealed only
      a few reports dealing with this complex problem, mostly resulting as a
      complication of diverticular disease of the colon. During a 4-month period, we
      diagnosed and successfully treated 2 women with a malignant colouterine fistula
      originating from a primary colorectal carcinoma invading the uterus. We herein
      report on our experience dealing with this kind of pathology, with special
      emphasis on the surgical technique used to resect the tumoral mass "en bloc".

PMID- 20130951
TI  - Clinical efficacy and safety of cefepime in febrile neutropenic patients with
      lung cancer.
AB  - Fever often occurs along with chemotherapy-induced neutropenia. This condition is
      referred to as febrile neutropenia (FN). Excellent guidelines for FN treatment
      have recently been published; however, there has so far been insufficient
      research concerning FN associated with solid tumors, especially in Japan. A multi
      institution prospective study of cefepime for the treatment of FN in lung cancer
      patients was conducted. The objective of this study was to determine the efficacy
      and safety of cefepime for FN in lung cancer patients. Cefepime (2 g x 2/day) was
      administered to patients with FN after treatment for lung cancer. The therapeutic
      response rate, the effect of the drug on pathogen populations, and the incidence
      of adverse effects were statistically analyzed. Twenty-one patients with FN were
      registered for this study. One case was excluded because of protocol violation;
      therefore, a total of 20 cases were analyzed. Three days after the administration
      of cefepime, improvement was evident in 15 cases. The response rate was 75%, 95%
      CI: 53.1-88.8. After 7 days, 17 patients experienced improvement in their
      condition (85%, 95% CI: 64.0-94.8). Carbapenem was eventually substituted for
      cefepime in three cases, and all cases finally displayed improvement. There was
      no mortality. Pathogens for FN were detected in three cases and they disappeared
      in one case. Four patients experienced adverse side effects, including skin
      eruption, serum bilirubin elevation, neutrophil depletion, and anterior chest
      pain. There were no severe adverse events. In this study, cefepime demonstrated a
      high degree of clinical efficacy and safety in the treatment of FN. Empiric
      monotherapy using cefepime is a recommended regimen for FN in patients with lung
      cancer in Japan.

PMID- 20130952
TI  - An experience at an ambulatory pediatric clinic during the first week of a
      confirmed H1N1 influenza outbreak in Kobe, Japan.

PMID- 20130953
TI  - Sporadic hemiplegic migraine and CREST syndrome.
AB  - Hemiplegic migraines are characterised by attacks of migraine with aura
      accompanied by transient motor weakness. There are both familial and sporadic
      subtypes, which are now recognised as separate entities by the International
      Classification of Headache Disorders, edition II (ICHD-II). The sporadic subtype
      has been associated with other medical conditions, particularly rheumatological
      diseases. We report the case of a woman with sporadic hemiplegic migraine
      associated with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal
      dysmotility, sclerodactyly and telangiectasia). Since there is a close
      relationship between migraine and Raynaud's phenomenon, it could be speculated
      that the sporadic hemiplegic migraines in our patient might be secondary to CREST
      syndrome.

PMID- 20130954
TI  - Climate change alters interannual variation of grassland aboveground
      productivity: evidence from a 22-year measurement series in the Inner Mongolian
      grassland.
AB  - Climate change is known to influence interannual variation in grassland
      aboveground net primary productivity (ANPP), or seasonal biomass, but direct,
      long-term ground observations are rare. We present a 22-year (1982-2003)
      measurement series from the Inner Mongolia grassland, China, to examine the
      effect of climate change on interannual variations in ANPP and monthly
      aboveground biomass (MAB). ANPP exhibited no increase over 1982-2003 but there
      was an association with previous-year precipitation. MAB in May increased by
      21.8% from 47.8 g m(-2) (averaged for 1982-1984) to 58.2 g m(-2) (2001-2003),
      whereas there was no significant variation in June, July and August, and a
      decrease of 29.7% in September. The MAB increase in May was correlated with
      increases in precipitation and temperature in the preceding months. These
      findings suggest that the effects of climate change on grassland production vary
      throughout the growing season, with warmer and wetter springs resulting in
      increased biomass early in the growing season, and drier falls causing a decrease
      in biomass late in the growing season.

PMID- 20130957
TI  - Is ventriculomegaly in idiopathic normal pressure hydrocephalus associated with a
      transmantle gradient in pulsatile intracranial pressure?
AB  - PURPOSE: In patients with idiopathic normal pressure hydrocephalus (iNPH) and
      ventriculomegaly, examine whether there is a gradient in pulsatile intracranial
      pressure (ICP) from within the cerebrospinal fluid (CSF) of cerebral ventricles
      (ICP(IV)) to the subdural (ICP(SD)) compartment. We hypothesized that pulsatile
      ICP is higher within the ventricular CSF. METHODS: The material includes 10
      consecutive iNPH patients undergoing diagnostic ICP monitoring as part of pre
      operative work-up. Eight patients had simultaneous ICP(IV) and ICP(SD) signals,
      and two patients had simultaneous signals from the lateral ventricle (ICP(IV))
      and the brain parenchyma (ICP(PAR)). Intracranial pulsatility was characterized
      by the wave amplitude, rise time, and rise time coefficient; static ICP was
      characterized by mean ICP. RESULTS: None of the patients demonstrated gradients
      in pulsatile ICP, that is, we found no evidence of higher pulsatile ICP within
      the CSF of the cerebral ventricles (ICP(IV)), as compared to either the subdural
      (ICP(SD)) compartment or within the brain parenchyma (ICP(PAR)). During
      ventricular infusion testing in one patient, the ventricular ICP (ICP(IV)) was
      artificially increased, but this increase in ICP(IV) produced no gradient in
      pulsatile ICP from the ventricular CSF (ICP(IV)) to the parenchyma (ICP(PAR)).
      CONCLUSIONS: In this cohort of iNPH patients, we found no evidence of transmantle
      gradient in pulsatile ICP. The data gave no support to the hypothesis that
      pulsatile ICP is higher within the CSF of the cerebral ventricles (ICP(IV)) than
      within the subdural (ICP(SD)) compartment or the brain parenchyma (ICP(PAR)) in
      iNPH patients.

PMID- 20130956
TI  - Ordered transcriptional factor recruitment and epigenetic regulation of tnf-alpha
      in necrotizing acute pancreatitis.
AB  - Tauhe expression of the critical initiator cytokine TNF-alpha was strongly
      upregulated in vivo in acute necrotic pancreatitis (AP) in rodents and in vitro
      in TNF-alpha activated acinar AR42J cells. Upregulation of tnf-alpha, inos, icam
      1 and il-6 occurred both in TNF-alpha receptor 1 and 2 knock-out mice, but not in
      TNF-alpha knock-out mice, in cerulein-induced acute pancreatitis. Chromatin
      immunoprecipitation analysis showed that transcriptional factors (ELK-1, SP1, NF
      kappaB and EGR-1) and chromatin modification complexes (HDAC1, HDAC2, GCN5, PCAF
      and CBP) were recruited and/or released from the promoter in a strictly ordered
      mechanism. Activation of tnf-alpha gene was also accompanied by an ordered
      increased level of histone H3K9, H3K14 and H3K18-acetylation and H3K4
      methylation, as well as H4K5 acetylation. A better knowledge of the molecular
      mechanisms that control tnf-alpha gene regulation will provide deeper
      understanding of the initiation and development of the inflammatory processes
      occurring in acute pancreatitis triggered by TNF-alpha cytokine.

PMID- 20130958
TI  - A short illustrated review of sellar region schwannomas.
AB  - INTRODUCTION: In this short illustrated review, we present the case of a frontal
      lobe schwannoma without cranial nerve or sellar attachment and a sellar
      schwannoma which mimicked a pituitary adenoma. LITERATURE REVIEW: We review the
      rare occurrence of sellar region schwannomas, their clinical presentation,
      operative management, outcomes, and the possible pathogenesis. ANALYSIS: The
      absence of Schwann cells in the central nervous system and the absence of
      neighboring cranial nerves in these two cases raise issues of the pathogenesis of
      these rare but curious lesions.

PMID- 20130959
TI  - Spatial variation in an avian host community: implications for disease dynamics.
AB  - Because many pathogens can infect multiple host species within a community,
      disease dynamics in a focal host species can be affected by the composition of
      the host community. We examine the extent to which spatial variation in species'
      abundances in an avian host community may contribute to geographically varying
      prevalence of a recently emerged wildlife pathogen. Mycoplasma gallisepticum is a
      pathogen novel to songbirds that has caused substantial mortality in house
      finches (Carpodacus mexicanus) in eastern North America. Though the house finch
      is the primary host species for M. gallisepticum, the American goldfinch (Spinus
      tristis) and northern cardinal (Cardinalis cardinalis) are alternate hosts, and
      laboratory experiments have demonstrated M. gallisepticum transmission between
      house finches and goldfinches. Still unknown is the real world impact on disease
      dynamics of variation in abundances of the three hosts. We analyzed data from
      winter-long bird and disease surveys in the northeastern United States. We found
      that higher disease prevalence in house finches was associated with higher
      numbers of northern cardinals and American goldfinches, although only the effect
      of cardinal abundance was statistically significant. Nevertheless, our results
      indicate that spatial variation in bird communities has the potential to cause
      geographic variation in disease prevalence in house finches.

PMID- 20130960
TI  - Perifosine selectively induces cell cycle block and modulates retinoblastoma and
      E2F1 protein levels in p53 mutated leukemic cell lines.
AB  - The effect of the single-chain alkylphospholipid perifosine was analyzed in
      p53(wild-type) (SKW6.4, OCI and MOLM), p53(mutated) (BJAB, MAVER) and p53(null)
      (HL-60) leukemic cell lines. Perifosine promoted cytotoxicity with a combination
      of apoptosis induction in all cell lines and cell cycle block at the G(2)M
      checkpoint, which was selectively observed in p53(mutated) BJAB and MAVER cell
      lines. At the molecular level, perifosine induced hypophosphorylation of
      retinoblastoma protein and the degradation of E2F1 protein in p53(mutated) but
      not in p53(wild-type) cells. These data indicate that perifosine potentially
      represents an innovative therapeutic approach for p53(mutated) hematological
      malignancies.

PMID- 20130961
TI  - Design of new secreted phospholipase A2 inhibitors based on docking calculations
      by modifying the pharmacophore segments of the FPL67047XX inhibitor.
AB  - Docking calculations that allow the estimation of the binding energy of small
      ligands in the GIIA sPLA(2) active site were used in a structure-based design
      protocol. Four GIIA sPLA(2) inhibitors co-crystallised with the enzyme, were used
      for examining the enzyme active site and for testing the FlexX in SYBYL 6.8
      molecular docking program to reproduce the crystallographic experimental data.
      The FPL67047XX inhibitor was chosen as a prototype structure for applying free
      energy perturbation (FEP) studies. Structural modifications of the initial
      structure of the FPL67047XX inhibitor (IC(50) 0.013 microM) were performed in an
      effort to optimise the interactions in the GIIA sPLA(2) active site. The
      structural modifications were based on: (1) the exploration of absolute
      configuration (i.e. comparison of the binding score of (R)- and (S)-enantiomers);
      (2) bioisosterism (i.e. replacement of the carboxylate group with the
      bioisosteric sulphonate and phosphonate groups); (3) insertion of substituents
      that fit better in the active site. The generated new structures exhibited higher
      binding energy. Such structures may spark off the interest of medicinal chemists
      for synthesizing potentially more active GIIA sPLA(2) inhibitors.

PMID- 20130962
TI  - The oxidative stress: endoplasmic reticulum stress axis in cadmium toxicity.
AB  - Cadmium preferentially accumulates in the kidney, the major target for cadmium
      related toxicity. Several underlying mechanisms are postulated, and reactive
      oxygen species (ROS) have been considered as crucial mediators for tissue
      injuries. In addition to oxidative stress, we recently disclosed that endoplasmic
      reticulum (ER) stress also plays a critical role. Cadmium causes ER stress in
      vitro and in vivo and mediates induction of apoptosis in target tissues. In this
      article, we describe a role for ER stress and involvement of particular branches
      of the unfolded protein response (UPR) in cadmium-triggered tissue injury,
      especially nephrotoxicity. We also discuss relationship between oxidative stress
      and ER stress, and involvement of selective ROS in the induction of pro-apoptotic
      branches of the UPR.

PMID- 20130963
TI  - Cloning, expression and characterization of Kunming mice lactoferrin and its N
      lobe.
AB  - The lactoferrin cDNA of Kunming mice was isolated by reverse transcription
      polymerase chain reaction and cloned into vector pET28a(+). Its deduced amino
      acid sequence was analyzed and compared with lactoferrin of other species. Its
      secondary and tertiary structure are predicted and modeled by bioinformatics
      tools online. Then recombinant Kunming mice lactoferrin and its N-lobe were both
      expressed successfully in the Escherichia coli BL21(DE3) in the form of inclusion
      bodies. After purification with Ni-NTA His-Bind resin, the yield of recombinant
      lactoferrin was 17 mg l(-1) with purity of 92.1%, and that of lactoferrin N-lobe
      was 20 mg l(-1) with purity of 98.5%. The inhibition efficiency of refolded
      lactoferrin N-lobe against Staphylococcus aureus ATCC 25923 reaches 48.6% at the
      concentration of 25 micromol l(-1). However, the refolded lactoferrin (12.5
      micromol l(-1)) didn't display obvious inhibition activity in the test. The
      expression of recombinant Kunming mice lactoferrin and its N-lobe will be helpful
      for the study of lactoferrin on structure, function and application in a mouse
      model system.

PMID- 20130964
TI  - microRNAs and lung cancer: tumors and 22-mers.
AB  - Work over the last decade has revealed novel regulatory mechanisms in
      pathological disease states that are mediated by microRNAs and has inspired
      researchers to begin elucidating the specific roles of miRNAs in the regulation
      of genes involved in cancer development and progression. Recently, miRNAs have
      been explored as therapeutic targets and diagnostic markers of cancer. In this
      paper, we review recent advances in the study of miRNAs involved in
      tumorigenesis, focusing on miRNA regulation of genes that have been demonstrated
      to play critical roles in lung cancer development. We discuss miRNA regulation of
      genes that play critical roles in the process of malignant transformation,
      angiogenesis and tumor metastasis, the dysregulation of miRNA expression in
      cancer development, and the development of miRNA-based diagnostics and
      therapeutics.

PMID- 20130965
TI  - School performance as a predictor of adulthood obesity: a 21-year follow-up
      study.
AB  - We examined the impact of school performance measured in terms of grade point
      averages (GPAs) in early and middle adolescence (ages 9, 12, and 15), and the
      impact of school performance throughout the different school stages on adult
      obesity. The participants were 732 healthy women and men derived from a
      population-based Cardiovascular Risk in Young Finns Study. GPAs were measured at
      the ages of 9, 12, and 15. The body mass index (BMI; kg/m(2)), and the waist
      circumference (WC) were conducted participants being aged 27 or 30. Birth weight,
      childhood BMI, adulthood physical activity, maternal and paternal BMI, and
      maternal education were controlled for. The results showed that low GPAs in each
      measurement and low GPAs throughout the comprehensive school were a risk factor
      of adulthood obesity, but only among women. The association remained when
      controlling for potential confounding variables (p-values in the fully adjusted
      models 0.026, 0.007, and 0.004 at the ages of 9, 12, and 15, respectively). The
      results were similar when the BMI was used as a dichotomous variable (BMI > or =
      30 and BMI < 30). Low school performance has previously been associated with
      higher rates of smoking and alcohol consumption later in life. Our result
      underscores that low school performance is a health risk factor that should be
      taken seriously in preventive health education.

PMID- 20130966
TI  - DNA methylation profiles of organic anion transporting polypeptide 1B3 in cancer
      cell lines.
AB  - PURPOSE: Multispecific organic anion transporter, OATP1B3/SLCO1B3, is expressed
      in several cancer cell lines as well as tumor tissues, and its expression
      sensitizes the cells to some anti-cancer agents. The present study was aimed to
      characterize the DNA methylation profiles around the transcriptional start site
      (TSS) of OATP1B3 and correlate them with the mRNA expression in cancer and
      immortalized cell lines. METHODS: The mRNA expression and DNA methylation
      profiles of OATP1B3 were determined by RT-PCR and bisulfite sequencing,
      respectively. RESULTS: The expression of OATP1B3 mRNA was detected in DLD-1, TFK
      1, PK-8, and PK-45P cells, but below the limit of detection in HepG2, Caco-2, and
      HEK293 cells. Bisulfite sequencing demonstrated that CpG dinucleotides around the
      TSS are differentially methylated among cell lines and partly associated with the
      mRNA expression profile of OATP1B3. Furthermore, treatment with 5-aza-2'
      deoxycytidine, an inhibitor of DNA methyltransferase, significantly increased the
      mRNA expression of OATP1B3 in HepG2 and Caco-2 cells by 18- and 14-fold,
      respectively, but not in DLD-1 and TFK-1 cells. CONCLUSION: DNA methylation
      dependent gene silencing is at least partly involved in the regulation of OATP1B3
      expression in cancer/immortalized cell lines.

PMID- 20130967
TI  - Oxygen monitoring during low flow anaesthesia.

PMID- 20130968
TI  - Changes in R-Wave amplitude in DII lead is less sensitive than pulse pressure
      variation to detect changes in stroke volume after fluid challenge in ICU
      patients postoperatively to cardiac surgery.
AB  - OBJECTIVE: The amplitude of R-wave in DII lead (RDII) has been shown to correlate
      to central blood volume in animal and healthy volunteers. The aim of this study
      was to assess if change in RDII (DeltaRDII) after passive leg rise (PLR) and
      fluid loading would allow detecting preload dependence in intensive care
      ventilated patients. This parameter was compared to concomitant changes in pulse
      arterial pressure (DeltaPP). METHODS: Observational study in 40 stable sedated
      and ventilated cardiac surgery patients studied postoperatively. In line with our
      routine practice we performed a 45 degrees passive leg rise (PLR1) to detect
      preload dependence. If cardiac index or DeltaPP rose more than 12 and 13%,
      respectively, the patient was declared as non-responder (NR) to fluid loading. If
      these criteria were not met, they were declared as responders (R) and received a
      500 ml of gelatin fluid loading (FL) followed by a second passive leg rise
      (PLR2). Hemodynamic parameters were assessed during each maneuver using their
      indwelling Swan-Ganz and radial catheter. RESULTS: We identified 16 R and 24 NR
      whose hemodynamic parameters did not differ at basal condition, except DeltaPP
      (19% +/- 7 in R vs. 7% +/- 4 in NR, P < 0.001). PLR1 did not elicit any
      hemodynamic change in NR. In R, DeltaPP decreased and SV rose, both significantly
      (P < 0.001) whereas DeltaRDII did not vary. FL induced a more pronounced change
      in these parameters. CONCLUSIONS: DeltaRDII in response to PLR does not
      successfully help identifying preload dependent patients contrarily to DeltaPP or
      change in stroke volume.

PMID- 20130969
TI  - Anesthetic agent vapor analyzers and propellants of pressurized meter-dose
      inhalers.
AB  - Anesthetic agent analyzers fail when drug from a HFA propelled pMDI is
      administered. Most anesthetic vapor analyzers use infrared absorption at 3.3
      micron. At this wavelength, substance like methane has been reported to interfere
      with the accuracy of measurement of anesthetic vapor. The anesthetic gas monitor
      1304 (Bruel and Kjaer) which functions at 10.3-13 micron wavelength was not
      affected by methane. Is it possible, HFA with its structural similarity to
      inhaled anesthetic agents may be responsible for faulty reading of anesthetic
      vapor concentration in two of our monitors? Further evidence is needed to support
      this finding. Anesthesiologists need to be ever vigilant and recognize the need
      for smarter designs of anesthetic agent analyzers with changing array of drugs
      administered during anesthetic management.

PMID- 20130970
TI  - IL-17 contributes to the development of chronic rejection in a murine heart
      transplant model.
AB  - BACKGROUND: Although interleukin-17 (IL-17) has been reported to participate in
      the pathogenesis of infectious, autoimmune and allergic disorders, the precise
      role in allograft rejection remains uncertain. This study illustrates that IL-17
      contributes to the pathogenesis of chronic allograft rejection. RESULT: Utilizing
      a murine heterotopic heart transplant model system, IL-17-deficient recipient
      mice had decreased allograft inflammatory cell recruitment, decreased IL-6, MCP
      1, and KC production, and reduced graft coronary artery disease (GCAD).
      Intragraft gamma delta (gammadelta) T cells appear to be the predominant source
      of IL-17 production. CONCLUSION: Therefore, IL-17 neutralization may provide a
      potential target for novel therapeutic treatment for cardiac allograft rejection.

PMID- 20130971
TI  - Following a calorie-restricted diet may help in reducing healthcare students' fat
      phobia.
AB  - Data from National Health and Nutrition Examination Survey 2005/2006 show that
      32.7% of US adults are overweight (BMI 25.0-29.9), 34.3% are obese (BMI 30-39.9),
      and 5.9% are extremely obese (BMI >or= 40). For the first time, the number of
      obese American adults is greater than those who are merely overweight. Negative
      attitudes and fat phobia toward the overweight exist not only in the general
      population, but also among health professionals including dietitians and
      dietetics students. The purpose of this study was to determine if fat phobia
      might be reduced among future professionals by putting students on a calorie
      restricted diet for a short period. Forty dietetics and health promotion students
      enrolled in a university obesity course completed the Fat Phobia Scale test
      before and after following a calorie restricted diet for 1 week (1,200 calories
      and 1,500 calories for women and men, respectively). Students also reflected
      their thoughts about following such a diet via brief journal entries. Results
      showed the change in fat phobias after following a calorie-restricted diet was
      significant. Many journal entries reflected a newfound respect for individuals
      struggling to lose weight and change in prior negative attitudes. Students
      reported that this experience would impact their future dealings with
      overweight/obese clients. It may be useful to incorporate this type of activity
      into the training of nutrition and other health professional students to increase
      sensitivity and reduce existing biases and negative attitudes toward
      overweight/obese clients.

PMID- 20130972
TI  - Now everyone looks the same: alcohol intoxication reduces the own-race bias in
      face recognition.
AB  - Several factors influence the reliability of eyewitness identification evidence.
      Typically, recognition for same-race faces is better than for different-race
      faces (the own-race bias), and alcohol intoxication decreases overall face
      recognition accuracy. This research investigated how alcohol intoxication
      influences the own-race bias. Asian and European participants completed tests of
      recognition memory for Asian and European faces when either mildly intoxicated
      (mean breath alcohol concentration of .05) or when sober. Compared to their sober
      counterparts, intoxicated participants showed a reduced own-race bias.
      Specifically, alcohol intoxication had a larger negative effect on the
      recognition of same-race faces compared to different-race faces. The legal and
      theoretical implications of these results are discussed.

PMID- 20130973
TI  - National identity of high-school adolescents in an era of socio-economic change:
      Russia and Ukraine in the post-perestroika period.
AB  - This study focuses on the national identity of high-school adolescents in Russia
      and Ukraine in the post-perestroika period. Adolescents studying in public high
      schools in 12 medium-size and large cities completed questionnaires in 1999 (n =
      468) and 2007 (n = 646). Russian adolescents consistently reported a more
      positive attitude towards their country and a stronger identification with the
      nation than did Ukrainian adolescents. The effect of socio-economic changes on
      the two components of national identity differed: the adolescents reported a more
      positive attitude towards their country in 2007 than in 1999, while their
      identification with the nations did not change significantly. Social support
      received from peers was associated with a more positive attitude towards the
      country and a stronger identification with the nation, while social support
      received from parents and teachers was not related to the national identity of
      adolescents. Adolescents' better psychological adjustment was associated with a
      more positive attitude towards the country but was not related to their
      identification with the nation. Adolescents who belonged to the ethnic majority
      reported a more positive attitude towards the country and a stronger
      identification with the nation as compared to adolescents who belonged to ethnic
      minorities.

PMID- 20130974
TI  - Encoding of brain state changes in local field potentials modulated by motor
      behaviors.
AB  - Local field potentials (LFPs) measure aggregate neural activity resulting from
      the coordinated firing of neurons within a local network. We hypothesized that
      state parameters associated with the underlying brain dynamics may be encoded in
      LFPs but may not be directly measurable in the signal temporal and spectral
      contents. Using the Kalman filter we estimated latent state changes in LFPs
      recorded in monkey motor cortical areas during the execution of a visually
      instructed reaching task, under different applied force conditions. Prior to the
      estimation, matched filtering was performed to decouple behavior-relevant signals
      (Stamoulis and Richardson, J Comput Neurosci, 2009) from unrelated background
      oscillations. State changes associated with baseline oscillations appeared
      insignificant. In contrast, state changes estimated from LFP components
      associated with the execution of movement were significant. Approximately
      direction-invariant state vectors were consistently observed. Their patterns
      appeared invariant also to force field conditions, with a peak in the first 200
      ms of the movement interval, but exponentially decreasing to the zero state
      approximately 200 ms from movement onset, also the time at which movement
      velocity reached its peak. Thus, state appeared to be modulated by the dynamics
      of movement but neither by movement direction nor by the mechanical environment.
      Finally, we compared state vectors estimated using the Kalman filter to the basis
      functions obtained through Principal Component Analysis. The pattern of the
      estimated state vector was very similar to that of the first PCA component,
      further suggesting that LFPs may directly encode brain state fluctuations
      associated with the dynamics of behavior.

PMID- 20130975
TI  - A pilot study of maternal sensitivity in the context of emergent autism.
AB  - Unstructured mother-toddler interactions were examined in 18-month-old high- and
      low-risk children subsequently diagnosed (n = 12) or not diagnosed (n = 21) with
      autism spectrum disorders (ASD) at 36 months. Differences in maternal sensitivity
      were not found as a function of emergent ASD status. A differential
      susceptibility moderation model of child risk guided investigations linking
      maternal sensitivity to child behavior and language growth. Group status
      moderated the relation between sensitivity and concurrent child behavior
      problems, with a positive association present for children with emergent ASD.
      Maternal sensitivity at 18 months predicted expressive language growth from age 2
      to 3 years among children with emergent ASD only. Findings underscore the
      importance of understanding parent-child interaction during this key period in
      the development of autism symptomatology.

PMID- 20130976
TI  - The relation between sexual orientation and suicide attempts in Austria.
AB  - Previous studies indicate that homosexual or bisexual individuals are at a higher
      risk of attempting suicide compared to heterosexuals. To overcome biases in these
      studies, more rigorous definitions of "suicide attempts" and the assessment of
      multiple dimensions of sexual orientation are needed. In addition, studies from
      the German speaking region are sparse, especially those not recruiting
      participants from the gay or lesbian communities. We solicited self-reported
      suicide attempts among 1,382 Austrian adults recruited through structured
      snowball sampling from students' social networks. Suicide attempts were more
      frequently reported by those participants with homosexual or bisexual fantasies,
      partner preference, behavior, and self-identification, compared to their
      heterosexually classified counterparts. This was true for any dimension of sexual
      orientation and for suicide attempts with intent to die or suicide attempts that
      required medical treatment. Our Austrian study confirmed existing evidence that
      homosexual and bisexual individuals are at an increased risk for attempting
      suicide. This should be considered in suicide preventive efforts.

PMID- 20130977
TI  - Developmental shifts in the behavioral phenotypes of inbred mice: the role of
      postnatal and juvenile social experiences.
AB  - The interaction between genotype and environment is an important feature of the
      process of development. We investigate this interaction by examining the
      influence of postnatal cross-fostering and post-weaning cross-housing on the
      behavioral development of 129S and B6 mice. Following cross-fostering, we found
      significant alterations in the frequency of maternal care as a function of
      maternal strain and pup type as well as interactions between these variables. In
      adulthood, we find there are sex-specific and strain-specific alterations in
      anxiety-like behavior as a function of rearing environment, with males exhibiting
      more pronounced rearing-induced effects. Mixed-strain housing of weanlings was
      found to lead to alterations in home-cage social and feeding behavior as well as
      changes in adult anxiety-like responses of 129S mice. Anxiety-like behavior in B6
      mice was altered as a function of the interaction between housing condition and
      weaning weight. These data illustrate the complex pathways through which early
      and later social experiences may lead to variations in behavior.

PMID- 20130978
TI  - Reproductive factors and risk of contralateral breast cancer by BRCA1 and BRCA2
      mutation status: results from the WECARE study.
AB  - OBJECTIVE: Reproductive factors, such as early age at menarche, late age at
      menopause, and nulliparity are known risk factors for breast cancer. Previously,
      we reported these factors to be associated with risk of developing contralateral
      breast cancer (CBC). In this study, we evaluated the association between these
      factors and CBC risk among BRCA1 and BRCA2 (BRCA1/2) mutation carriers and non
      carriers. METHODS: The WECARE Study is a population-based multi-center case
      control study of 705 women with CBC (cases) and 1,397 women with unilateral
      breast cancer (controls). All participants were screened for BRCA1/2 mutations
      and 181 carriers were identified. Conditional logistic regression models were
      used to evaluate associations between reproductive factors and CBC for mutation
      carriers and non-carriers. RESULTS: None of the associations between reproductive
      factors and CBC risk differed between mutation carriers and non-carriers. The
      increase in risk with younger age at menarche and decrease in risk in women with
      more than two full-term pregnancies seen in non-carriers were not significantly
      different in carriers (adjusted RRs = 1.31, 95% CI 0.65-2.65 and 0.53, 95% CI
      0.19-1.51, respectively). No significant associations between the other
      reproductive factors and CBC risk were observed in mutation carriers or non
      carriers. CONCLUSION: For two reproductive factors previously shown to be
      associated with CBC risk, we observed similar associations for BRCA1/2 carriers.
      This suggests that reproductive variables that affect CBC risk may have similar
      effects in mutation carriers and non-carriers.

PMID- 20130979
TI  - Depressive symptoms among young breast cancer survivors: the importance of
      reproductive concerns.
AB  - Breast cancer diagnosis and treatment can negatively impact fertility in
      premenopausal women and influence reproductive planning. This study investigates
      whether concerns about reproduction after breast cancer treatment were associated
      with long-term depressive symptoms. Participants include 131 women diagnosed with
      early-stage breast cancer at age 40 or younger participating in the Women's
      Healthy Eating and Living (WHEL) Survivorship Study. Participants were enrolled
      an average of 1.5 years postdiagnosis and depressive symptoms were monitored 6
      times throughout the average additional 10 year follow-up period. Detailed recall
      of reproductive concerns after treatment was collected an average of 12 years
      postdiagnosis. Multilevel regression was used to evaluate whether mean long-term
      depressive symptoms differed as a function of reproductive concerns and
      significant covariates. Multilevel regression identified greater recalled
      reproductive concerns as an independent predictor of consistent depressive
      symptoms after controlling for both social support and physical health (B = 0.02,
      SE = 0.01, P = 0.04). In bivariate analyses, being nulliparous at diagnosis and
      reporting treatment-related ovarian damage were both strongly associated with
      higher reproductive concerns and with depressive symptoms. Reported reproductive
      concerns after breast cancer treatment were a significant contributor to
      consistent depressive symptoms. Younger survivors would benefit from additional
      information and support related to reproductive issues.

PMID- 20130980
TI  - Information from CTC measurements for metastatic breast cancer prognosis-we
      should do more than selecting an "optimal cut point".

PMID- 20130981
TI  - COMT Val158Met polymorphism and breast cancer risk: evidence from 26 case-control
      studies.
AB  - The Catechol-O-methyltransferase (COMT) plays an important role in the
      development of breast cancer. Many previous epidemiologic studies explored the
      association of COMT Val158Met polymorphism with breast cancer susceptibility.
      However, the results were inconsistent. We therefore performed a meta-analysis of
      26 published studies including 16,693 breast cancer patients and 18,261 healthy
      controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used
      to assess the strength of the association of the COMT Val158Met polymorphism with
      breast cancer risk. No significant association was found in all genetic models in
      overall, Asian, European populations. After the studies whose genotype
      frequencies in the controls did not fulfill Hardy-Weinberg equilibrium were
      excluded, we found a borderline significant decreased breast cancer risk among
      Europeans (for the recessive model LL versus HH/HL: OR = 0.90, 95% CI = 0.90
      1.00, P (heterogeneity) = 0.33). There was no between-study heterogeneity. In
      conclusion, COMT Val158Met polymorphism may be a low-penetrant risk factor for
      breast cancer development in European population.

PMID- 20130982
TI  - Population-based survival-cure analysis of ER-negative breast cancer.
AB  - This study investigated the trends over time in age and stage specific population
      based survival of estrogen receptor negative (ER-) breast cancer patients by
      examining the fraction of cured patients and the median survival time for uncured
      patients. Cause-specific survival data from the Surveillance, Epidemiology, and
      End Results program for cases diagnosed during 1992-1998 were used in mixed
      survival cure models to evaluate the cure fraction and the extension in survival
      for uncured patients. Survival trends were compared with adjuvant chemotherapy
      data available from an overlapping patterns-of-care study. For stage II N+
      disease, the largest increase in cure fraction was 44-60% (P = 0.0257) for women
      aged >or=70 in contrast to a 7-8% point increase for women aged <50 or 50-69 (P =
      0.056 and 0.038, respectively). For women with stage III disease, the increases
      in the cure fraction were not statistically significant, although women aged 50
      69 had a 10% point increase (P = 0.103). Increases in cure fraction correspond
      with increases in the use of adjuvant chemotherapy, particularly for the oldest
      age group. In this article, for the first time, we estimate the cure fraction for
      ER- patients. We notice that at age >o5r=70, the accelerated increase in cure
      fraction from 1992 to 1998 for women with stage II N+ compared with stage III
      suggests a selective benefit for chemotherapy in the lower stage group.

PMID- 20130983
TI  - Diagnostic value of vacuum-assisted breast biopsy for breast carcinoma: a meta
      analysis and systematic review.
AB  - As mammography screening has its limitation in diagnosis in breast carcinoma,
      minimally invasive procedures offer a better option. We conducted a systematic
      review to establish the overall value of Vacuum-assisted breast biopsy (VAB) for
      the diagnosis of breast cancer. After a review and quality assessment of 21
      studies, sensitivity, specificity and other measures of accuracy of VAB for
      evaluating breast lesions were pooled using random-effects models. Summary
      receiver operating characteristic curves were used to summarize overall accuracy.
      Underestimate rate of atypical ductal hyperplasia (ADH) and ductal carcinoma in
      situ (DCIS) were also calculated. The summary estimates for VAB in diagnosis of
      breast carcinoma were as follows: sensitivity, 0.981 (95% confidence interval
      [CI], 0.972-0.987); specificity, 0.999 (95% CI, 0.997-0.999); positive likelihood
      ratio (PLR), 93.84 (95% CI, 41.55-211.95); negative likelihood ratio, 0.05 (95%
      CI, 0.03-0.09); diagnostic odds ratio, 1891.7 (95% CI, 683.8-5233.4);
      underestimate rate of ADH and DCIS were 20.9% (95% CI, 0.177-0.245) and 11.2%
      (95% CI, 0.098-0.128), respectively. VAB is a highly sensitive and specific
      biopsy method for evaluating mammographically detected breast in women. To be on
      the safe side, the diagnosis of ADH in VAB warrants surgical excision.

PMID- 20130984
TI  - Mammographic density does not differ between unaffected BRCA1/2 mutation carriers
      and women at low-to-average risk of breast cancer.
AB  - Elevated mammographic density (MD) is one of the strongest risk factors for
      sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part,
      genetically determined; however, the relationship between MD and BRCA1/2 mutation
      status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers
      enrolled in the U.S. National Cancer Institute's Clinical Genetics Branch's
      Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk
      enrolled in the same study (n = 29) or the NCI/National Naval Medical Center's
      Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation
      negative members of mutation-positive families or women with no prior breast
      cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary
      breast cancer syndrome) and a Gail score <1.67. A single experienced mammographer
      measured MD using a computer-assisted thresholding method. We collected standard
      breast cancer risk factor information in both studies. Unadjusted mean percent MD
      was higher in women with BRCA1/2 mutations compared with women at low-to-average
      breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared
      after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We
      explored age at menarche, nulliparity, age at first birth, menopausal status,
      number of breast biopsies, and exposure to exogenous hormonal agents as potential
      confounders of the MD and BRCA1/2 association. Taking these factors into account
      did not significantly alter the results of the age/body mass index-adjusted
      analysis. Our results do not provide support for an independent effect of BRCA1/2
      mutation status on mammographic density.

PMID- 20130985
TI  - Association between HER2, TOP2A, and response to anthracycline-based preoperative
      chemotherapy in high-risk primary breast cancer.
AB  - In breast cancer, recent studies suggest that the value of HER2 for predicting
      response to anthracycline-based chemotherapy may be more likely related to the
      concomitant amplification of the TOP2A gene. Here, we study the association
      between HER2 or TOP2A status and response to anthracycline-based preoperative
      chemotherapy and explore the interaction between HER2 or TOP2A status and intense
      dose-dense (IDD) chemotherapy. HER2 and TOP2A gene alterations were quantified by
      fluorescence in situ hybridization in primary tumor core biopsies from 373 high
      risk primary breast cancer patients (tumors >/=3 cm or inflammatory) that
      received an IDD or conventionally scheduled anthracycline-based preoperative
      chemotherapy. HER2 was amplified in 94/350 tumors (27%) of which 40/94 (46%)
      demonstrated TOP2A amplification, and 17/94 (18%) TOP2A deletions. TOP2A gene
      alterations were not found in HER2 non-amplified cases. HER2 amplification was
      associated with a significantly higher pathologic complete response (pCR) rate
      only when TOP2A was co-amplified (30% vs. 11%, P = 0.002), but not when deleted
      (13% vs. 11%, P = 0.755), or normal (14% vs. 11%, P = 0.578) compared to HER2 non
      amplified tumors. In multivariate analysis, TOP2A amplification (odds ratio [OR]
      3.04, P = 0.021), but not HER2 amplification (OR 1.74, P = 0.170) was associated
      with a significantly higher pCR rate. No interaction was observed between HER2 or
      TOP2A status and IDD chemotherapy. TOP2A gene amplification may define a subset
      of HER2-amplified breast cancers that are responsible for the markedly improved
      chemosensitivity seen in HER2-positive breast cancer. However, added benefit of
      IDD chemotherapy itself was not associated with HER2 or TOP2A status.

PMID- 20130986
TI  - Global breast cancer seasonality.
AB  - Human breast cancer incidence has seasonal patterns that seem to vary among
      global populations. The aggregate monthly frequency of breast cancer diagnosis
      was collected and examined for 2,921,714 breast cancer cases diagnosed across 64
      global regions over spans from 2 to 53 years. Breast cancer is consistently
      diagnosed more often in spring and fall, both in the Northern and Southern
      Hemispheres, regardless of presumable menopausal status (<or=50, >50). This
      seasonality is increasingly more prominent as population distance from the
      equator increases and this latitude dependence is most pronounced among women
      living in rural areas. Moreover, the overall annual incidence (2005-2006), per
      100,000 population, of breast cancer increased as the latitude of population
      residence increased. These data make it clear that human breast cancer discovery
      occurs non-randomly throughout each year with peaks near both equinoxes and
      valleys near both solstices. This stable global breast cancer seasonality has
      implications for better prevention, more accurate screening, earlier diagnosis,
      and more effective treatment. This complex latitude-dependent breast cancer
      seasonality is clearly related to predictable local day/night length changes
      which occur seasonally. Its mechanism may depend upon seasonal sunlight mediation
      of vitamin D and seasonal mediation of nocturnal melatonin peak level and
      duration.

PMID- 20130987
TI  - Embryonic stem cells isolated from Atlantic cod (Gadus morhua) and the
      developmental expression of a stage-specific transcription factor ac-Pou2.
AB  - The establishment of embryonic stem cell cultures and the identification of
      molecular markers for undifferentiated embryonic stem cells (ESC) as well as
      differentiated cells types will open new opportunities in the study of
      developmental biology and for developing embryonic in vitro models of the
      ecologically and economically important fish specie Atlantic cod (Gadus morhua).
      We report here that cod blastula cells express a Class V POU gene known to be
      highly expressed in embryonic cell populations of vertebrates. The cod
      transcript, designated Atlantic cod-Pou2 (ac-Pou2), can be used as a genetic
      marker for cod blastula cells in vivo and in vitro. Using a quantitative real
      time PCR approach, we found that the ac-Pou2 transcript was downregulated before
      the egg reached the stage of gastrulation, the starting point of extensive cell
      differentiation. We also demonstrate the culturing of ESC isolated from cod
      blastula stage eggs. The cod ESC exhibited in vitro characteristics of
      pluripotency described for both mammalian ESC and fish ES-like cells (medaka,
      zebrafish, seabream, sea perch and rainbow trout). Cod ESC in culture expressed
      ac-pou2, differentiated spontaneously and had the ability to form embryoid bodies
      following retinoic acid treatment. The ESC could also be directed to
      differentiate.

PMID- 20130988
TI  - Impact of near-future ocean acidification on echinoderms.
AB  - As a consequence of increasing atmospheric CO(2), the world's oceans are warming
      and slowly becoming more acidic (ocean acidification, OA) and profound changes in
      marine ecosystems are certain. Calcification is one of the primary targets for
      studies of the impact of CO(2)-driven climate change in the oceans and one of the
      key marine groups most likely to be impacted by predicted climate change events
      are the echinoderms. Echinoderms are a vital component of the marine environment
      with representatives in virtually every ecosystem, where they are often keystone
      ecosystem engineers. This paper reviews and analyses what is known about the
      impact of near-future ocean acidification on echinoderms. A global analysis of
      the literature reveals that echinoderms are surprisingly robust to OA and that
      important differences in sensitivity to OA are observed between populations and
      species. However, this is modulated by parameters such as (1) exposure time with
      rare longer term experiments revealing negative impacts that are hidden in short
      or midterm ones; (2) bottlenecks in physiological processes and life-cycle such
      as stage-specific developmental phenomena that may drive the whole species
      responses; (3) ecological feedback transforming small scale sub lethal effects
      into important negative effects on fitness. We hypothesize that
      populations/species naturally exposed to variable environmental pH conditions may
      be pre-adapted to future OA highlighting the importance to understand and monitor
      environmental variations in order to be able to to predict sensitivity to future
      climate changes. More stress ecology research is needed at the frontier between
      ecotoxicology and ecology, going beyond standardized tests using model species in
      order to address multiple water quality factors (e.g. pH, temperature, toxicants)
      and organism health. However, available data allow us to conclude that near
      future OA will have negative impact on echinoderm taxa with likely significant
      consequences at the ecosystem level.

PMID- 20130989
TI  - Identification of cross-contaminated animal cells by PCR and isoenzyme analysis.
AB  - Animal cell lines have become very popular substrates for the production of
      vaccines and biopharmaceuticals. Characterization of candidate production cell
      lines is central to ensure product safety and maintenance of consistency in the
      manufacture of biologicals. Nested PCR and isoenzyme analysis have been used
      widely to prove the identity and purity of various cell lines and primary cells
      individually and also after deliberate cross-contamination. The nested PCR based
      on the Cytochrome b (Cyt b) gene of mitochondrial DNA (Mt DNA) was found to be
      more sensitive than isoenzyme analysis in detecting low levels of contaminants
      (as low as 1%). Interestingly, competition between different co-cultured cell
      lines has shown in one case that cross-contamination need not always results in a
      mixed cell population. The nested PCR technique for the Cyt b gene described in
      this study appears to be a potential replacement for isoenzyme analysis and here
      we demonstrate the PCR method used is sensitive and reliable for cell line
      authentication in a simple, rapid and reliable format to help assure the
      authenticity of cell substrates for the production of safe vaccines and
      biopharmaceuticals.

PMID- 20130990
TI  - The role of marital status, literacy, and urbanity in suicidal behavior by burns
      in the province of Khorasan, Iran.
AB  - A prospective study of all suicidal behaviors by burns requiring hospitalization
      was conducted in the province of Khorasan, Iran, from March 21, 2005 to March 20,
      2006, to examine marital status, urbanity and literacy among these patients. Data
      were obtained through interviews during the course of hospitalization. A total of
      130 patients with suicidal behavior by burns were identified (incidence rate of
      2.9 per 100,000). Females had a higher rate of suicidal behavior by burns than
      males (4.2 vs. 1.6 per 100,000, P < 0.001). The rate of suicidal behavior by
      burns was higher among single persons than married persons (4.3 vs. 3.5 per
      100,000). The rate of suicidal behavior by burns among the rural population was
      slightly higher than the urban population (3.2 vs. 2.7 per 100,000). The high
      rate of suicidal behavior by burns among young, married women in Khorasan is a
      social tragedy.

PMID- 20130992
TI  - Benign esophagopulmonary fistula through an epiphrenic diverticulum and
      asymptomatic achalasia.

PMID- 20130993
TI  - The cannabis hyperemesis syndrome characterized by persistent nausea and
      vomiting, abdominal pain, and compulsive bathing associated with chronic
      marijuana use: a report of eight cases in the United States.
AB  - GOALS/BACKGROUND: The cannabis hyperemesis syndrome, which is associated with
      chronic cannabis use, was recently reported in seven case reports and one
      clinical series of ten patients from Australia. We further characterize this
      syndrome with eight well-documented cases in the United States and report results
      of cannabis discontinuation and cannabis rechallenge. STUDY METHODS: Patients
      were identified by the three investigators in gastroenterology clinic or
      inpatient wards at William Beaumont Hospital from January to August 2009 based on
      chronic cannabis use; otherwise unexplained refractory, recurrent vomiting; and
      compulsive bathing. Charts were retrospectively analyzed with follow-up data
      obtained from subsequent physician visits and patient interviews. RESULTS: The
      eight patients on average were 32.4 +/- 4.1 years old. Five were male. The mean
      interval between the onset of cannabis use and development of recurrent vomiting
      was 19.0 +/- 3.7 years. Patients had a mean of 7.1 +/- 4.3 emergency room visits,
      5.0 +/- 2.7 clinic visits, and 3.1 +/- 1.9 admissions for this syndrome. All
      patients had visited at least one other hospital in addition to Beaumont
      Hospital. All patients had vomiting (mean vomiting episodes every 3.0 +/- 1.7 h),
      compulsive bathing (mean = 5.0 +/- 2.0 baths or showers/day; mean total bathing
      time = 5.0 +/- 5.1 h/day), and abdominal pain. Seven patients took hot baths or
      showers, and seven patients experienced polydipsia. Four out of five patients who
      discontinued cannabis use recovered from the syndrome, while the other three
      patients who continued cannabis use, despite recommendations for cessation,
      continued to have this syndrome. Among those four who recovered, one patient had
      recurrence of vomiting and compulsive bathing with cannabis resumption.
      CONCLUSIONS: Cannabis hyperemesis is characterized by otherwise unexplained
      recurrent nausea and vomiting, compulsive bathing, abdominal pain, and polydipsia
      associated with chronic cannabis use. This syndrome can occur in the United
      States as well as in Australia. Cannabis cessation may result in complete
      symptomatic recovery.

PMID- 20130994
TI  - Granulocyte colony-stimulating factor enhances bone marrow mononuclear cell
      homing to the liver in a mouse model of acute hepatic injury.
AB  - BACKGROUND: Experiments have reported that granulocyte colony stimulating factor
      (G-CSF) can mobilize stem cells. However, few studies have examined the effect of
      G-CSF on bone marrow mononuclear cell (BMMC) mobilization, in particular
      regarding their capability to home to acutely injured liver. AIMS: The aim of
      this study was to evaluate the effort of G-CSF on BMMC homing to the liver
      following chemically-induced hepatic failure. METHODS: BMMC were isolated from
      mice, pre-labeled with PKH26 and infused into the mice in which hepatic injury
      had been induced followed by administration of G-CSF or vehicle. Livers were
      studied by fluorescent microscopy after transplantation of pre-labeled BMMC.
      RESULTS: PKH26 labeled cells were found in liver tissue at 102 +/- 10 cells/high
      power field in the BMMC+G-CSF group and 30 +/- 5 cells/high power field in the
      BMMC group, but none in the G-CSF group and the control group (P < 0.05). In the
      former two groups the majority of PKH26 labeled cells colocalized with
      proliferative cell nuclear antigen (PCNA). The number of PCNA positive cells in
      the BMMC+G-CSF group was 20 +/- 4 cells/high power field, while in the BMMC group
      it was 14 +/- 2 cells/high power field, in the G-CSF group 12 +/- 2 cells/high
      power field, and 8 +/- 1 cells/high power field in the control group. Moreover,
      albumin expression was increased in the BMMC+G-CSF treated group (149 +/- 7/high
      power field) relative to the BMMC group (48 +/- 6/high power field), the G-CSF
      group (44 +/- 5/high power field) and the vehicle group (30 +/- 6/high power
      field), with the former three groups showing elevated levels as compared to
      vehicle control (30 +/- 6) (P < 0.05). CONCLUSION: Transplanted BMMC may home to
      injured liver, which appears to be enhanced by G-CSF administration.

PMID- 20130995
TI  - Equilibrium or disequilibrium? A dual-wavelength investigation of photosystem I
      donors.
AB  - Oxidation of photosystem I (PSI) donors under far-red light (FRL), slow re
      reduction by stromal reductants and fast re-reduction in the dark subsequent to
      illumination by white light (WL) were recorded in leaves of several C(3) plants
      at 810 and 950 nm. During the re-reduction from stromal reductants the mutual
      interdependence of the two signals followed the theoretical relationship
      calculated assuming redox equilibrium between plastocyanin (PC) and P700, with
      the equilibrium constant of 40 +/- 10 (Delta E (m) = 86-99 mV) in most of the
      measured 24 leaves of nine plant species. The presence of non-oxidizable PC of up
      to 13% of the whole pool, indicating partial control of electron transport by PC
      diffusion, was transiently detected during a saturation pulse of white light
      superimposed on FRL or on low WL. Nevertheless, non-oxidizable PC was absent in
      the steady state during fast light-saturated photosynthesis. It is concluded that
      in leaves during steady state photosynthesis the electron transport rate is not
      critically limited by PC diffusion, but the high-potential electron carriers PC
      and P700 remain close to the redox equilibrium.

PMID- 20130996
TI  - The chlorosome: a prototype for efficient light harvesting in photosynthesis.
AB  - Three phyla of bacteria include phototrophs that contain unique antenna systems,
      chlorosomes, as the principal light-harvesting apparatus. Chlorosomes are the
      largest known supramolecular antenna systems and contain hundreds of thousands of
      BChl c/d/e molecules enclosed by a single membrane leaflet and a baseplate. The
      BChl pigments are organized via self-assembly and do not require proteins to
      provide a scaffold for efficient light harvesting. Their excitation energy flows
      via a small protein, CsmA embedded in the baseplate to the photosynthetic
      reaction centres. Chlorosomes allow for photosynthesis at very low light
      intensities by ultra-rapid transfer of excitations to reaction centres and enable
      organisms with chlorosomes to live at extraordinarily low light intensities under
      which no other phototrophic organisms can grow. This article reviews several
      aspects of chlorosomes: the supramolecular and molecular organizations and the
      light-harvesting and spectroscopic properties. In addition, it provides some
      novel information about the organization of the baseplate.

PMID- 20130997
TI  - The "green" phylogenetic clade of Rieske/cytb complexes.
AB  - More than a decade ago, Heliobacteria were recognised to contain a Rieske/cytb
      complex in which the cytochrome b subunit is split into two separate proteins, a
      peculiar feature characteristic of the cyanobacterial and plastidic b (6) f
      complex. The common presence of RCI-type reaction centres further emphasise
      possible evolutionary links between Heliobacteria, Chlorobiaceae and
      Cyanobacteria. In this contribution, we further explore the evolutionary
      relationships among these three phototrophic lineages by both molecular phylogeny
      and consideration of phylogenetic marker traits of the superfamily of Rieske/cytb
      complexes. The combination of these two methods suggests the existence of a
      "green" clade involving many non-phototrophs in addition to the mentioned RCI
      type photosynthetic organisms. Structural and functional idiosyncrasies are (re
      )interpreted in the framework of evolutionary biology and more specifically
      evolutionary bioenergetics.

PMID- 20130998
TI  - Insights into heliobacterial photosynthesis and physiology from the genome of
      Heliobacterium modesticaldum.
AB  - The complete annotated genome sequence of Heliobacterium modesticaldum strain
      Ice1 provides our first glimpse into the genetic potential of the
      Heliobacteriaceae, a unique family of anoxygenic phototrophic bacteria. H.
      modesticaldum str. Ice1 is the first completely sequenced phototrophic
      representative of the Firmicutes, and heliobacteria are the only phototrophic
      members of this large bacterial phylum. The H. modesticaldum genome consists of a
      single 3.1-Mb circular chromosome with no plasmids. Of special interest are
      genomic features that lend insight to the physiology and ecology of
      heliobacteria, including the genetic inventory of the photosynthesis gene
      cluster. Genes involved in transport, photosynthesis, and central intermediary
      metabolism are described and catalogued. The obligately heterotrophic metabolism
      of heliobacteria is a key feature of the physiology and evolution of these
      phototrophs. The conspicuous absence of recognizable genes encoding the enzyme
      ATP-citrate lyase prevents autotrophic growth via the reverse citric acid cycle
      in heliobacteria, thus being a distinguishing differential characteristic between
      heliobacteria and green sulfur bacteria. The identities of electron carriers that
      enable energy conservation by cyclic light-driven electron transfer remain in
      question.

PMID- 20130999
TI  - Context of entry and number of depressive symptoms in an older Mexican-origin
      immigrant population.
AB  - We examined the association between context of entry into the United States and
      symptoms of depression in an older age Mexican-origin population. We found that
      context of entry was associated with the number of depressive symptoms reported
      in this population. Specifically, immigrants who arrived to the U.S. following
      the Mexican Revolution (1918-1928) reported significantly fewer depressive
      symptoms, and those who arrived following enactment of the Immigration Reform
      Control Act (1965-1994) reported significantly more symptoms of depression,
      compared to those who arrived in the Bracero era (1942-1964). These findings
      suggest that sociopolitical context at the time of immigration may be associated
      with long-term psychological well-being. They contribute to a growing body of
      literature that suggests that the context of immigration may have long-term
      implications for the health of immigrant populations. We discuss implications of
      our findings for understanding relationships between immigration policies and the
      health of Mexican immigrant populations.

PMID- 20131000
TI  - Explanatory models of health and disease among South Asian immigrants in Chicago.
AB  - To identify concepts of health and disease as part of a study on designing
      culturally-targeted heart disease prevention messages for South Asians. We
      conducted qualitative, semi-structured interviews in English, Hindi and Urdu with
      75 respondents from a federally qualified health center and at a community center
      for South Asian immigrants in Chicago, Illinois. Age ranged from 20 to 70 years;
      60% were women; 60% held advanced degrees; 70% migrated to the US in the last 10
      years; and 60% of the interviews were in Hindi or Urdu. Concepts of health and
      disease fell into four domains: behavioral, physical, psycho-social and
      spiritual. Muslim participants consistently evoked spiritual factors such as
      faith and prayer. Women more frequently included performing home duties and
      positive affect in their concept of health. Men more frequently cited behavioral
      factors such as smoking and drinking as the cause of disease. Many South Asians
      have a holistic conceptualization of health and disease, incorporating spiritual,
      physical and psycho-social factors. Health promotion strategies aimed at South
      Asians in the US should take into account this holistic model of health and
      disease, while also recognizing that variations exist within South Asians, by
      gender and religion.

PMID- 20131001
TI  - Editorial.

PMID- 20131002
TI  - Aquatic birnavirus capsid protein, VP3, induces apoptosis via the Bad-mediated
      mitochondria pathway in fish and mouse cells.
AB  - Aquatic birnavirus induces post-apoptotic necrotic cell death via a newly
      synthesized protein-dependent pathway. However, the involvement of viral genome
      encoded protein(s) in this death process remains unknown. In the present study,
      we demonstrated that the submajor capsid protein, VP3, up-regulates the pro
      apoptotic protein, Bad, in fish and mouse cells. Western blot analysis revealed
      that VP3 was expressed in CHSE-214 cells at 4 h post-infection (pi), indicating
      an early role during viral replication. We cloned the VP3 gene and tested its
      function in fish and mouse cells; VP3 overexpression induced apoptotic cell death
      by TUNEL assay. In addition, it up-regulated Bad gene expression in zebrafish ZLE
      cells by threefold at 12 h post-transfection (pt) and in mouse NIH3T3 cells by
      tenfold at 24 h pt. VP3 up-regulation of Bad expression altered mitochondria
      function, inducing mitochondrial membrane potential (MMP) loss and activating
      initiator caspase-9 and effector caspase-3. Furthermore, reduced Bad expression
      (65% reduction), MMP loss (up to 40%), and enhanced cell viability (up to 60%)
      upon expression of VP3 antisense RNA in CHSE-214 cells at 24 h post-IPNV
      infection was observed. Finally, overexpression of the anti-apoptotic gene, zfBcl
      xL, reduced VP3-induced apoptotic cell death and caspase-3 activation at 24 h in
      fish cells. Taken together, these results suggest that aquatic birnavirus VP3
      induces apoptosis via up-regulation of Bad expression and mitochondrial
      disruption, which activates a downstream caspase-3-mediated death pathway that is
      blocked by zfBcl-xL.

PMID- 20131004
TI  - Mitochondrial dynamics, cell death and the pathogenesis of Parkinson's disease.
AB  - The structure and function of the mitochondrial network is regulated by
      mitochondrial biogenesis, fission, fusion, transport and degradation. A well
      maintained balance of these processes (mitochondrial dynamics) is essential for
      neuronal signaling, plasticity and transmitter release. Core proteins of the
      mitochondrial dynamics machinery play important roles in the regulation of
      apoptosis, and mutations or abnormal expression of these factors are associated
      with inherited and age-dependent neurodegenerative disorders. In Parkinson's
      disease (PD), oxidative stress and mitochondrial dysfunction underlie the
      development of neuropathology. The recessive Parkinsonism-linked genes PTEN
      induced kinase 1 (PINK1) and Parkin maintain mitochondrial integrity by
      regulating diverse aspects of mitochondrial function, including membrane
      potential, calcium homeostasis, cristae structure, respiratory activity, and
      mtDNA integrity. In addition, Parkin is crucial for autophagy-dependent clearance
      of dysfunctional mitochondria. In the absence of PINK1 or Parkin, cells often
      develop fragmented mitochondria. Whereas excessive fission may cause apoptosis,
      coordinated induction of fission and autophagy is believed to facilitate the
      removal of damaged mitochondria through mitophagy, and has been observed in some
      types of cells. Compensatory mechanisms may also occur in mice lacking PINK1
      that, in contrast to cells and Drosophila, have only mild mitochondrial
      dysfunction and lack dopaminergic neuron loss. A better understanding of the
      relationship between the specific changes in mitochondrial dynamics/turnover and
      cell death will be instrumental to identify potentially neuroprotective pathways
      steering PINK1-deficient cells towards survival. Such pathways may be manipulated
      in the future by specific drugs to treat PD and perhaps other neurodegenerative
      disorders characterized by abnormal mitochondrial function and dynamics.

PMID- 20131003
TI  - Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic
      implications.
AB  - The ubiquitin/proteasome pathway is the major proteolytic quality control system
      in cells. In this review we discuss the impact of a deregulation of this pathway
      on neuronal function and its causal relationship to the intracellular deposition
      of ubiquitin protein conjugates in pathological inclusion bodies in all the major
      chronic neurodegenerative disorders, such as Alzheimer's, Parkinson's and
      Huntington's diseases as well as amyotrophic lateral sclerosis. We describe the
      intricate nature of the ubiquitin/proteasome pathway and discuss the paradox of
      protein aggregation, i.e. its potential toxic/protective effect in
      neurodegeneration. The relations between some of the dysfunctional components of
      the pathway and neurodegeneration are presented. We highlight possible
      ubiquitin/proteasome pathway-targeting therapeutic approaches, such as activating
      the proteasome, enhancing ubiquitination and promoting SUMOylation that might be
      important to slow/treat the progression of neurodegeneration. Finally, a model
      time line is presented for neurodegeneration starting at the initial injurious
      events up to protein aggregation and cell death, with potential time points for
      therapeutic intervention.

PMID- 20131005
TI  - Modulation of pro-survival proteins by S-nitrosylation: implications for
      neurodegeneration.
AB  - Nitric oxide (NO) is a gaseous signaling molecule in the biological system. It
      mediates its function through the direct modification of various cellular
      targets, such as through S-nitrosylation. The process of S-nitrosylation involves
      the attachment of NO to the cysteine residues of proteins. Interestingly, an
      increasing number of cellular pathways are found to be regulated by S
      nitrosylation, and it has been proposed that this redox signaling pathway is
      comparable to phosphorylation in cells. However, imbalance of NO metabolism has
      also been linked to a number of human diseases. For instance, NO is known to
      contribute to neurodegeneration by causing protein nitration, lipid peroxidation
      and DNA damage. Moreover, recent studies show that NO can also contribute to the
      process of neurodegeneration through the impairment of pro-survival proteins by S
      nitrosylation. Thus, further understanding of how NO, through S-nitrosylation,
      can compromise neuronal survival will provide potential therapeutic targets for
      neurodegenerative diseases.

PMID- 20131006
TI  - Validation of a new contrast material protocol adapted to body surface area for
      optimized low-dose CT coronary angiography with prospective ECG-triggering.
AB  - In patients with large total blood volume contrast material (CM) dilution
      decreases coronary attenuation in CT coronary angiography (CTCA). As increased
      blood volume is well paralleled by body surface area (BSA) we assessed a BSA
      adapted CM protocol to compensate for dilution effects. Low-dose CTCA with
      prospective ECG-triggering was performed in 80 patients with a BSA-adapted CM
      bolus ranging 40-105 ml and injection rate ranging 3.5-5.0 ml/s for a BSA of
      <1.70 to >or=2.5 m(2). Eighty control patients matched for BSA who had previously
      undergone routine CTCA with a fixed CM protocol of 80 ml at 5 ml/s served as
      reference group. The average vessel attenuation from the proximal right (RCA) and
      the left main coronary artery (LMA) was assessed. Correlation of BSA with vessel
      attenuation was assessed in both groups. BSA-matching of all patients was
      successful (BSA-adapted group 1.98 +/- 0.15 m(2), range 1.66-2.39 m(2) versus
      reference group 1.98 +/- 0.17 m(2), range 1.59-2.38 m(2); P = 0.74). Mean CM
      bolus was significantly smaller in the BSA-adapted versus the reference group
      (70.9 +/- 14.1 vs. 80.0 +/- 0 ml, P < 0.001). There was no correlation in the BSA
      adapted group (r = -0.07, P = 0.53, SEE = 0.15), while coronary attenuation was
      inversely related to BSA in the reference group (r = -0.59, P < 0.001, SEE =
      0.14). We have successfully validated a BSA-adapted contrast material protocol
      which results in a comparable coronary contrast enhancement independent of
      individual BSA. This was achieved despite a significant reduction in the overall
      contrast material amount.

PMID- 20131007
TI  - Central role of real-time three-dimensional echocardiography in the assessment of
      intracardiac thrombi.
AB  - The current study was designed to evaluate the feasibility and clinical utility
      of real-time 3-dimensional echocardiography (RT3DE) for detection of intracardiac
      thrombi with comparison to 2-dimensional echocardiography (2DE). The study
      included 45 consecutive patients with intracardiac thrombi detected by routine
      2DE (mean age 45 +/- 8.4 years, 75% males). The relevant features of the thrombus
      by 2DE and RT3DE (site, shape, and number) were assessed according to a
      subjective four-point score index for image quality (1 = not visualized, 2 =
      inadequate, 3 = sufficient and 4 = excellent). Measurements included: maximum
      diameter and volume. 2DE and RT3DE detected 45 thrombi (34 in the left ventricle,
      six in the left atrium, four in the left atrial appendage, four in the right
      atrium, and two in the right ventricle). RT3DE could detect seven additional
      thrombi in five patients (three in the left atrial appendage and four in the left
      ventricular apex). Visualization score by 2DE and RT3DE was comparable (Kappa
      index: 7.2). RT3DE measurements of maximum diameter were well correlated with 2DE
      (R(2) = 0.88, P < 0.01) and showed better interobserver agreement than 2DE (2.88,
      -1.92 vs. 5.33, -3.87, respectively). RT3DE was superior to 2DE for assessment of
      thrombus mobility, differentiation between the thrombus and myocardium, and
      delineation of the changes in thrombi structure, e.g. calcification,
      degeneration, or lysis. In addition, volume calculation could be obtained by
      RT3DE only. IN CONCLUSION: RT3DE is comparable to 2DE for the assessment of the
      intracardiac thrombi and provided more detailed information beyond the scope of
      the established 2DE.

PMID- 20131008
TI  - Sequencing and characterization of the porcine alpha-galactosidase A gene:
      towards the generation of a porcine model for Fabry disease.
AB  - Fabry disease is an inherited lysosomal disorder caused by a deficiency of alpha
      galactosidase A (alpha-gal A). The systemic accumulation of substrate, mainly
      globotriaosylceramide (Gb3), results in organ failure. Although Gb3 accumulation
      has been observed in an alpha-gal A-deficient mouse model, important clinical
      manifestations were not seen. The pursuit of effective treatment for Fabry
      disease through gene therapy, for example, has been hampered by the lack of a
      relevant large animal model to assess the efficacy and safety of novel therapies.
      Towards assembling the tools to generate an alternative animal model, we have
      sequenced and characterized the porcine ortholog of the alpha-gal A gene. When
      compared to the human alpha-gal A, the porcine alpha-gal A showed a high level of
      homology in the coding regions and located at chromosome Xq22. Cell lysate and
      supernatants from Fabry patient-derived fibroblasts transduced with a lentiviral
      vector (LV) carrying the porcine alpha-gal A cDNA (LV/porcine alpha-gal A),
      showed high levels of alpha-gal A activity and its enzymological stability was
      similar to that of human alpha-gal A. Uptake of secreted porcine alpha-gal A was
      observed into non-transduced cells and was partially inhibited by soluble mannose
      6-phosphate. Furthermore, Gb3 accumulation was reduced in Fabry patient-derived
      fibroblasts transduced with the LV/porcine alpha-gal A. In conclusion, we
      elucidated and characterized the porcine alpha-gal A gene and enzyme. Similarity
      in enzymatic profile and chromosomal location between alpha-gal A of porcine and
      human origins may be of great advantage for the development of a large animal
      model for Fabry disease.

PMID- 20131009
TI  - Cloning, chromosomal localization, expression profile and association analysis of
      the porcine WNT10B gene with backfat thickness.
AB  - The Wingless-type MMTV integration site (Wnt) family encodes secreted
      glycoproteins that are ligands for the frizzled family of seven-transmembrane
      receptors and the low density lipoprotein receptor-related protein family of co
      receptors. The WNT10B gene inhibits differentiation of preadipocytes in vitro and
      impairs adipose development in vivo. In the present study, a 1,615-bp cDNA
      sequence of the porcine WNT10B gene was obtained by RT-PCR. The porcine WNT10B
      gene was assigned to 5p11-p15 by using the somatic cell hybrid panel (SCHP) and
      the radiation hybrid (IMpRH) panel. One SNP in the 3'-untranslated region (3'
      UTR) was found and association analysis suggested that the SNP was associated
      with backfat thickness. Semi-quantitative RT-PCR showed that the porcine WNT10B
      gene was expressed in all tissues examined in 35d and adult pigs and the mRNA
      expression of WNT10B in fat tissue of Tongcheng pigs was dramatically higher than
      that in Large White pigs.

PMID- 20131010
TI  - Complete mitochondrial DNA sequence and phylogenetic analysis of Zhikong scallop
      Chlamys farreri (Bivalvia: Pectinidae).
AB  - The complete mitochondrial genome of Zhikong scallop Chlamys farreri is 21,695 bp
      in length and contains 12 protein-coding genes (the atp8 gene is absent, as in
      most bivalves), 2 ribosomal RNA genes, and 22 transfer RNA genes. The heavy
      strand has an overall A+T content of 58.7%. GC and AT skews for the mt genome of
      C. farreri are 0.337 and -0.184, respectively, indicating the nucleotide bias
      against C and A. The mitochondrial gene order of C. farreri differs drastically
      from the scallops Argopecten irradians, Mimachlamys nobilis and Placopecten
      magellanicus, which belong to the same family Pectinidae. 6623 bp non-coding
      nucleotides exist intergenically in the mitogenome of C. farreri, with a large
      continuous sequence (4763 bp) between tRNA ( Val ) and tRNA ( Asn ). Two repeat
      families are found in the large continuous sequence, which seems to be a common
      feature of scallops. Phylogenetic analysis based on 12 concatenated amino acid
      sequences of protein-coding genes supports the monophyly of Pectinidae and
      paraphyletic Pteriomorphia with respect to Heteroconchia.

PMID- 20131011
TI  - Molecular characterization and expression analysis of a heat shock protein 90
      gene from disk abalone (Haliotis discus).
AB  - Heat shock protein 90s (hsp90s) are chaperones that contribute to the proper
      folding of cellular proteins and help animals cope with the cellular protein
      damages in stress conditions. In this study, an hsp90 gene was isolated from disc
      abalone (Haliotis discus). The complete nucleotide sequence of the hsp90 gene
      contains an open reading frame of 2,184 base pairs, encoding an 84 kDa protein.
      Disk abalone hsp90 shares high sequence similarity with other hsp90 family
      proteins. Although the phylogenetic analysis did not classify it into the
      hsp90alpha group, the inductivity of this gene was confirmed by heat shock and
      lipopolysaccharide (LPS) challenge test. Disk abalone hsp90 gene displayed a
      rapid and reversible induction response to both an exposure of typical heat shock
      and the LPS challenge. Once given the sublethal heat shock treatment, the
      transcription of disk abalone hsp90 gene was significantly up-regulated. With a
      recovery of 12 h, the transcription of disk abalone hsp90 gene gradually
      attenuated to the control level. These observations reflected the feedback
      regulation of abalone heat shock responses faithfully. In response to LPS
      challenge, the transcription of disk abalone hsp90 gene was significantly
      increased within 2 h and it approached maximum induction at 4 h later and
      recovered finally the reference level in 24 h. Take all together, the cloning and
      expression analysis of disk abalone hsp90 gene provided useful molecular
      information of abalone responses in stress conditions and potential ways to
      monitor the chronic stressors in abalone culture environments and diagnose the
      animal health status.

PMID- 20131012
TI  - Optimists doing something different: a patient's view of geneQOL research.
AB  - This is a Patient Voice commentary for the GeneQOL special issue.

PMID- 20131013
TI  - Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus.
AB  - BACKGROUND: The role of liver resection in patients with hepatocellular carcinoma
      (HCC) accompanying with portal vein tumor thrombus (PVTT) remains controversial.
      This article aimed to evaluate the significance of different location and extent
      of PVTT on surgical outcomes after liver resection for HCC. MATERIALS AND
      METHODS: A retrospective study was carried out on patients who underwent partial
      hepatectomy with or without portal thrombectomy for HCC with PVTT in a single
      tertiary center from January 2001 to December 2003. According to the extent, PVTT
      was divided into 4 types (I-segmental/sectoral branches of portal vein, II-left
      and/or right portal vein, III-main portal vein trunk, and IV-superior mesenteric
      vein). RESULTS: A total of 406 patients with HCC and PVTT who underwent partial
      hepatectomy were studied. The complication rate and hospital mortality rate were
      32.8 and 0.2%, respectively. After a median follow-up of 6.4 months, 128 patients
      (31.5%) died. The 1- and 3-year overall survival rates were 34.4 and 13.0%,
      respectively. The 1- and 3-year disease-free survival rates were 13.3 and 4.7%,
      respectively. Patients with PVTT located in the segmental, sectoral, or right
      and/or left portal veins (types I and II) showed significantly better survival
      than those with PVTT extended to the main trunk of the portal vein or the
      superior mesenteric vein (types III and IV). CONCLUSIONS: Liver resection is
      justified in selected patients with PVTT located in the segmental or sectoral
      branches of the portal vein. However, surgical resection for PVTT involving the
      portal bifurcation or the main trunk is still controversial.

PMID- 20131014
TI  - Risk factors for lymph node metastasis from gastric cancers with submucosal
      invasion.
AB  - BACKGROUND: Accurate prediction of the metastatic status of lymph nodes (LNs) is
      clinically important for selecting treatment strategies in patients with gastric
      cancer with submucosal invasion (GCSM). In this study, we determined the risk
      factors for lymph node metastasis (LNM), including micrometastasis, in patients
      with GCSM. MATERIALS AND METHODS: A total of 5610 LNs dissected from 189 patients
      with GCSM who had undergone a standard gastrectomy were immunostained with CAM
      5.2 monoclonal antibody to detect LN micrometastasis. Clinicopathological risk
      factors for lymph node metastasis (LNM), including micrometastasis, were
      determined. RESULTS: LNM was detected in 216 LNs (107 macroscopic metastases, 72
      micrometastases, and 37 isolated tumor cells) in 55 (29.1%) of the 189 patients
      with GCSM. A multivariate analysis revealed that a tumor size of more than 20 mm,
      a mixed- or undifferentiated-type histology, a vertical tumor invasion depth in
      the submucosal layer (VTIDSM) of more than 0.5 mm, and the presence of lymphatic
      vessel invasion (LVI) were independent risk factors for LNM. The incidences of
      LNM in patients with 0, 1, 2, 3, and 4 risk factors were 0, 4.5, 11.4, 36.1, and
      52.9%, respectively. Among the patients with only 1 or 2 risk factors, all the
      metastatic lesions were located only in the first tier. On the other hand, LNM in
      the second tier was also detected in 24.5% of the patients with more than 3 risk
      factors. CONCLUSIONS: Tumor size, histologic type, VTIDSM, and LVI are important
      risk factors for predicting the presence and extent of LNM in patients with GCSM.

PMID- 20131015
TI  - Downstaging without complete pathologic response after neoadjuvant treatment
      improves cancer outcomes for cIII but not cII rectal cancers.
AB  - BACKGROUND: The aim of this study was to evaluate whether downstaging impacts
      prognosis in patients with cII versus cIII rectal cancer. MATERIALS AND METHODS:
      We identified from our colorectal cancer database 295 patients with primary cII
      and cIII rectal cancer staged by CT and ERUS/MRI who received 5-FU-based
      chemoradiation followed by R0 surgery after a median interval of 7 weeks during
      1997-2007. The median radiotherapy dose was 5040 cGy. We excluded 58 patients
      with pathologic complete response (pCR) and compared among the remaining 162
      patients pathologic downstaging (cII to ypI, cIII to ypII or ypI) versus no
      pathologic downstaging (c stage < or = yp stage). Outcomes evaluated were 5-year
      overall survival, 3-year cancer-specific survival, disease-free survival, overall
      recurrence, local recurrence, and distant recurrence. RESULTS: The median age was
      58 years and median follow-up was 48 months. Patients with downstaging versus no
      downstaging were statistically comparable with respect to demographics,
      chemoradiation regimen, interval time between neoadjuvant chemoradiation and
      surgery, tumor distance from anal verge, surgical procedures performed, and
      follow-up time. With the exception of local recurrence rates, downstaging
      resulted in significantly improved cancer outcomes for cIII but not cII.
      CONCLUSIONS: Downstaging without pCR is a significant prognostic factor for
      patients with stage cIII rectal cancer. Tumor response to neoadjuvant
      chemoradiation should be taken into account when defining the optimal adjuvant
      chemotherapy regimen for patients with cIII rectal cancer.

PMID- 20131016
TI  - Altered expression of E-cadherin by hepatocyte growth factor and effect on the
      prognosis of nasopharyngeal carcinoma.
AB  - BACKGROUND AND PURPOSE: Hepatocyte growth factor (HGF)-related E-cadherin
      expression and prognosis of patients with nasopharyngeal carcinoma (NPC) are not
      fully understood. This study investigated HGF-induced altered expression of E
      cadherin and the relationship between prognosis and modulation of E-cadherin by
      HGF in NPC. METHODS: 135 cases of NPC were collected, and expression of HGF, c
      Met, and E-cadherin in tissue microarray was evaluated by immunohistochemical
      staining. Correlation between immunostainings and clinicopathological parameters,
      as well as the follow-up data of patients, was analyzed statistically. The
      association and alteration of E-cadherin by HGF treatment in NPC cell lines were
      evaluated by immunocytochemical staining, Western blot, and invasion assay.
      RESULTS: Both high HGF expression in tumor cells (62.9%, 85/135 cases) and
      nonmembranous E-cadherin expression (61.5%, 83/135 cases) were significantly
      associated with advanced clinical stage, lymph node metastasis, and worse
      prognosis of NPC patients. However, only abnormal E-cadherin expression (P =
      0.001) and lymph node metastasis (P = 0.004) emerged as strong independent
      prognostic factors for overall survival of NPC patients. In vitro, exogenous HGF
      decreased and internalized E-cadherin expression from cell membrane to cytoplasm,
      with obvious cellular morphological change. HGF-treated NPC cells exhibited
      significantly enhanced invasive ability in Matrigel matrix-coated Transwell
      chamber assay. CONCLUSION: HGF may contribute to cell invasion in NPC by
      modulating E-cadherin-mediated cell-cell adhesion through downregulation and
      internalization of E-cadherin. Altered expression of E-cadherin by HGF is a
      valuable predictor for prognostic evaluation of NPC patients.

PMID- 20131017
TI  - Validation study of the s classification for melanoma patients with positive
      sentinel nodes: the Montreal experience.
AB  - BACKGROUND: Standard of care is to perform a complete lymph node dissection
      (CLND) in melanoma patients with positive sentinel lymph nodes (SLNs). However,
      less than 20% will have metastases in non-SLNs. The S classification was
      described to predict the non-SLN status, hoping to identify a subset of patients
      who can be spared the CLND. We tried to validate the feasibility and usefulness
      of this classification. MATERIALS AND METHODS: We performed a retrospective chart
      review. All melanoma cases between 1996 and 2006 were included, and 359 patients
      with SLN biopsies were identified. All pathology slides were reviewed with an
      emphasis on the S classification. RESULTS: There were 365 SLN biopsies performed.
      A total of 82 patients (22.8%) had positive SLNs, while 277 patients (77.2%) had
      negative SLNs. There were 22 patients classified as SI, 18 as SII, 37 as SIII,
      and 5 were unclassified. On CLND, only 10 patients (12.2%) had positive non-SLNs.
      None of these were classified as SI while 2 patients (11%) were classified as SII
      and 8 (22%) as SIII. The S category was found to be a predictor of non-SLN
      status, and this reached statistical significance (P = 0.044). On univariate
      analysis, only an increasing Breslow depth and ulceration were predictive of a
      non-SI status. CONCLUSION: Our results suggest that the S classification is
      easily feasible and predicts the status of non-SLNs. No patient with SI status
      was found to have additional non-SLN positive nodes. A larger-scale, prospective
      trial should be done to confirm these results and possibly spare patients the
      morbidity of CLND with a positive SLN.

PMID- 20131018
TI  - Evaluating recruitment among female sex workers and injecting drug users at risk
      for HIV using respondent-driven sampling in Estonia.
AB  - Few recent publications have highlighted theoretical and methodological
      challenges using respondent-driven sampling (RDS). To explore why recruitment
      with RDS may work in some populations and not in others, we assess the
      implementation of RDS to recruit female sex workers (FSWs) and injection drug
      users (IDUs) into a human immunodeficiency virus biological and risk behavior
      survey in Tallinn, Estonia. Recruitment of FSWs was slower and more challenging
      than that of IDUs. The IDU study recruited 350 participants within 7 weeks, while
      the FSW study recruited 227 participants over 28 weeks. Implementation
      modifications that did not negatively impact key RDS theoretical and
      methodological requirements were used to improve recruitment during the FSW
      study. We recommend that all RDS studies include a formative research process to
      involve the participation of target populations and key persons associated with
      these populations in the study planning and throughout the implementation
      processes to improve recruitment from the outset and to respond to poor
      recruitment during data collection.

PMID- 20131019
TI  - Fetal bovine serum concentration affects delta9 desaturase activity of
      Trypanosoma cruzi.
AB  - Fetal bovine serum (FBS) is an important factor in the culture of Trypanosoma
      cruzi, since this parasite obtains and metabolizes fatty acids (FAs) from the
      culture medium, and changes in FBS concentration reduce the degree of
      unsaturation of FAs in phosphoinositides. When T. cruzi epimastigotes were
      cultured with 5% instead of 10% FBS, and stearic acid was used as the substrate,
      (9) desaturase activity decreased by 50%. Apparent K (m) and V (m) values for
      stearic acid, determined from Lineaweaver-Burk plots, were 2 microM and 219
      pmol/min/mg of protein, respectively. In studies of the requirement for reduced
      pyridine nucleotide, (9) desaturase activity reached a maximum with 8 microM NADH
      and then remained constant; the apparent K (m) and V (m) were 4.3 microM and 46.8
      pmol/min/mg of protein, respectively. The effect of FBS was observed only for (9)
      desaturase activity; (12) desaturase activity was not affected. The results
      suggest that decreased FBS in culture medium is a signal that modulates (9)
      desaturase activity in T. cruzi epimastigotes.

PMID- 20131020
TI  - Effect of oppositely charged polymer and dissolution media on rheology of spray
      dried ionic complexes.
AB  - The purpose of this research was to address the utility of rheological study in
      understanding the influence of oppositely charged polymers on release of naproxen
      sodium encapsulated in chitosan particles. The interaction between oppositely
      charged kappa-carrageenan (kappa-Ca) and chitosan leads to relatively higher gel
      strength, which is proportional to the ability to retard the drug release at
      acidic pH. The oscillatory tests within the linear viscoelastic range where the
      stress is proportional to the applied strain were performed on the hydrated
      sample matrices containing chitosan-naproxen sodium spray-dried complexes and k
      Ca or hydroxypropyl methylcellulose (HPMC) in various ratios. It was observed
      that the effect of pH change on the dynamic moduli in spray-dried complexes
      containing kappa-Ca was much stronger than that with HPMC reflecting presence of
      strong ionic interaction between kappa-Ca and chitosan. The combination of
      oppositely charged polymers in different ratios proved to be useful in modulating
      the rheological properties of the hydrated formulations and their release
      retarding properties. Dynamic moduli can be used to measure gel strength and are
      significant for the interpretation of oral sustained release spray-dried
      complexes.

PMID- 20131022
TI  - Is there a role for tissue biopsy in the diagnosis of periprosthetic infection?
AB  - BACKGROUND: Successful treatment of an infected joint arthroplasty depends on
      correctly identifying the responsible pathogens. The value of a preoperative
      biopsy remains controversial. QUESTIONS/PURPOSES: We (1) compared the sensitivity
      and specificity of both tests separately and in combination, and (2) asked
      whether the combination of tissue biopsy and aspiration would improve our
      diagnostic yield in the evaluation of periprosthetic joint infections. PATIENTS
      AND METHODS: We prospectively followed 120 patients with suspected infection of a
      total joint arthroplasty: 64 with THAs and 56 with TKAs. All patients had
      aspiration with culture and biopsy. RESULTS: The sensitivity was 83% for
      aspiration, 79% for biopsy, and 90% for the combination of both techniques. The
      specificity was 100% for aspiration and biopsy and the combination. The overall
      accuracy was 84%, 81%, and 90%, respectively. CONCLUSIONS: Our data suggest
      tissue biopsy alone offers no clear advantage over joint aspiration. However, the
      combination of both techniques provides improved sensitivity and accuracy. We
      recommend the use of tissue biopsy as an adjunct to joint aspiration in the
      diagnosis of total joint infection. LEVEL OF EVIDENCE: Level II, diagnostic
      study. See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 20131023
TI  - Primary medication non-adherence: analysis of 195,930 electronic prescriptions.
AB  - BACKGROUND: Non-adherence to essential medications represents an important public
      health problem. Little is known about the frequency with which patients fail to
      fill prescriptions when new medications are started ("primary non-adherence") or
      predictors of failure to fill. OBJECTIVE: Evaluate primary non-adherence in
      community-based practices and identify predictors of non-adherence. PARTICIPANTS:
      75,589 patients treated by 1,217 prescribers in the first year of a community
      based e-prescribing initiative. DESIGN: We compiled all e-prescriptions written
      over a 12-month period and used filled claims to identify filled prescriptions.
      We calculated primary adherence and non-adherence rates for all e-prescriptions
      and for new medication starts and compared the rates across patient and
      medication characteristics. Using multivariable regressions analyses, we examined
      which characteristics were associated with non-adherence. MAIN MEASURES: Primary
      medication non-adherence. KEY RESULTS: Of 195,930 e-prescriptions, 151,837 (78%)
      were filled. Of 82,245 e-prescriptions for new medications, 58,984 (72%) were
      filled. Primary adherence rates were higher for prescriptions written by primary
      care specialists, especially pediatricians (84%). Patients aged 18 and younger
      filled prescriptions at the highest rate (87%). In multivariate analyses,
      medication class was the strongest predictor of adherence, and non-adherence was
      common for newly prescribed medications treating chronic conditions such as
      hypertension (28.4%), hyperlipidemia (28.2%), and diabetes (31.4%). CONCLUSIONS:
      Many e-prescriptions were not filled. Previous studies of medication non
      adherence failed to capture these prescriptions. Efforts to increase primary
      adherence could dramatically improve the effectiveness of medication therapy.
      Interventions that target specific medication classes may be most effective.

PMID- 20131024
TI  - Primary hydatid cyst of the biceps femoris.
AB  - Echinococciasis is a zoonotic infestation, which generally involves the liver and
      the lungs. Primary muscle hydatidosis is an uncommon finding. The authors report
      a case of primary hydatid cyst localized in the right long head of the biceps
      femoris of a 25-year-old woman. A wide excision of the cyst with a safety margin
      was performed. No recurrence has been detected after a 3-year follow-up period.
      The authors review the literature and discuss the MRI findings. The diagnosis of
      muscular hydatid cyst is done using clinical and radiological findings in endemic
      context.

PMID- 20131025
TI  - Right ventricular stiffness constant as a predictor of postoperative hemodynamics
      in patients with hypoplastic right ventricle: a theoretical analysis.
AB  - One and a half ventricle repair (1.5VR) is a surgical option for hypoplastic
      right ventricle (RV). The benefits of this procedure compared to biventricular
      repair (2VR) or Fontan operation remain unsettled. To compare postoperative
      hemodynamics, we performed a theoretical analysis using a computational model
      based on lumped-parameter state-variable equations. We varied the RV stiffness
      constant (B (RV)) to simulate the various RV hypoplasia, and estimated
      hemodynamics for a given B (RV). With B (RV) < 150% of normal, cardiac output was
      the largest in 2VR. With B (RV) > 150%, cardiac output became larger in 1.5VR
      than in 2VR. With B (RV) > 250%, RV end-diastolic volume was almost the same
      between 1.5VR and 2VR, and a rapid increase in atrial pressure precluded the use
      of 1.5VR. These results indicate that the beneficial effect of 1.5VR depends on
      the RV stiffness constant. Determination of management strategy should not only
      be based on the morphologic parameters but also on the physiological properties
      of RV.

PMID- 20131026
TI  - Exploration of key points in evaluation criteria of Chinese medicine in the
      treatment of cancer.

PMID- 20131027
TI  - The importance of the differentiating syndromes for the efficacy assessment of
      Chinese medicine in the treatment of cancer.

PMID- 20131028
TI  - Could we use clinical benefit to evaluate the effects of chinese medicine on the
      treatment of cancer?

PMID- 20131029
TI  - The application of assessment of the quality of life in the clinical efficacy
      evaluation system and the selection of questionnaires of Chinese medicine
      treating tumors.

PMID- 20131030
TI  - Effect of Yiqi Yangyin Decoction on the quality of life of patients with unstable
      angina pectoris.
AB  - OBJECTIVE: To observe the effect of Yiqi Yangyin Decoction (, YQYYD) on the
      quality of life (QOL) of patients with unstable angina pectoris (UAP). METHODS: A
      total of 108 patients with UAP of qi-yin deficiency syndrome confirmed by
      coronary angiography were enrolled and assigned to the treated group (treated
      with YQYYD and conventional therapy of Western medicine) and the control group
      (treated with conventional therapy of Western medicine), by the use of the PROC
      PLAN of the SAS 6.12 software, in a prospective, randomized, controlled design.
      The clinical total effective rate, symptom score, QOL scale [Seattle Angina
      Questionnaire (SAQ)] and incidence of important clinical events were defined as
      the observation indices to evaluate the interventional effect of YQYYD on the QOL
      of patients with UAP of the qi-yin deficiency syndrome. RESULTS: During the
      study, three cases dropped out in the treated group, one case dropped out in the
      control group, and 104 cases, including 51 cases in the treatment group and 53
      cases in the control group, finished the trial. After four weeks of treatment,
      the total clinical effective rates in the treated group and the control group
      were 80.4% and 75.5% respectively, and there was no obvious difference between
      them (P>0.05). However, the symptom score of the treated group (9.31 + or - 2.02)
      was significantly lesser than that of the control group (11.62 + or - 3.04,
      P<0.05), and the total score of the QOL scale of the treated group (68.76 + or -
      5.74) was significantly higher than that of the control group (61.06 + or - 3.31,
      P<0.01). Among those in the treated group physical limitation, angina stability,
      angina frequency, and treatment satisfaction were significantly ameliorated when
      compared with the control group after treatment (P<0.05, P<0.01). The incidence
      of important clinical events in the treated group (3.9%) was lower than that in
      the control group (5.7%) during the 8-month follow-up period, but the difference
      was insignificant (P>0.05). CONCLUSION: YQYYD could improve the clinical symptoms
      of patients with UAP of qi-yin deficiency syndrome and greatly improve their QOL.

PMID- 20131031
TI  - Effect of Chinese medicine therapy for strengthening-Pi and nourishing-Shen in
      preventing lamivudine induced YMDD mutation and its immunologic mechanism.
AB  - OBJECTIVE: To observe the effect of Chinese medicine therapy for strengthening-Pi
      and nourishing-Shen (SPNS) in preventing lamivudine induced YMDD mutation and its
      immunological mechanism. METHODS: One hundred and sixty chronic hepatitis B (CHB)
      patients with positive HBeAg were equally assigned to two groups at random: the
      observation group and the control group. Patients in the observation group were
      treated with lamivudine combined with SPNS, and those in the control group were
      treated with lamivudine only, with the treatment lasting for 52 weeks in total.
      Changes in indexes, including liver function, HbeAg, HBV-DNA, YMDD variation,
      CD(4), CD(4)/CD(8) ratio, interferon-gamma (IFN-gamma), interleukin-4 (IL-4),
      blood routine, renal function, as well as any adverse reactions that occurred in
      patients, were observed at different time points. RESULTS: The ALT, AST recovery
      rate and HBV-DNA negatively inversing rate at the 24th week, the 36th week and
      the 52nd week were all higher (P<0.05); meanwhile, the YMDD mutation rate at the
      36th week and the 52nd week was lower (P<0.05) in the observation group than in
      the control group. The posttreatment levels of CD(4), CD(4)/CD(8) ratio, IFN
      gamma, and IL-4 as well as the pre-post treatment difference of these indexes in
      the observation group were significantly different from those in the control
      group (P<0.05). CONCLUSION: Chinese medicine SPNS therapy can significantly
      reduce the YMDD variation of HBV, and the mechanism may be related to its
      regulation of the CD(4) level, CD(4)/CD(8) ratio and Th1/Th2 balance.

PMID- 20131032
TI  - Treatment of non-alcoholic fatty liver disease by Qianggan Capsule.
AB  - OBJECTIVE: To observe the therapeutic effect and safety of Qianggan Capsule (QGC)
      in treating non-alcoholic fatty liver disease (NAFLD), using polyene
      phosphatidylcholine capsule (PPC) as a reference. METHODS: Eighty-eight patients
      with NAFLD were randomly assigned to two groups, 45 in the treatment group
      treated with QGC and 43 in the control group treated with PPC. The course of
      treatment lasted for 6 months. Changes in liver function, blood lipids, and
      iconographic indexes before and after treatment were observed, and clinical
      efficacy was evaluated. RESULTS: In the treatment group, alanine aminotransferase
      (ALT) was lowered significantly from 56.02 + or - 32.59 IU/L before treatment to
      38.27 + or - 22.68 IU/L after treatment, and CT liver/spleen ratio significantly
      increased from 0.69 + or - 0.18 to 0.91 + or - 0.25, showing statistical
      significance (P<0.05); in contrast, the corresponding changes of the two indexes
      in the control group were 56.56 + or - 26.33 IU/L to 49.67 + or - 26.22 IU/L, and
      0.66 + or - 0.20 to 0.75 + or - 0.24, respectively, the pre-post treatment
      difference showing insignificant difference (P>0.05). No severe adverse reactions
      occurred during the whole treatment course. CONCLUSION: QGC is an effective and
      safe remedy for the treatment of NAFLD.

PMID- 20131033
TI  - Clinical observation on the endocrinal and immune functions in subjects with yin
      deficiency constitution.
AB  - OBJECTIVE: To explore the relationship between yin-deficiency constitution (YDC)
      and biochemical indexes by way of observing the endocrinal and immune functions
      in subjects with YDC. METHODS: On the basis of epidemiological investigation, 60
      subjects with YDC and 50 with gentle constitution (GC) were selected according to
      the pertinent criteria. From each subject, 8 mL of fasting venous blood was drawn
      at 8:00-9:00 in the morning, with the serum separated by centrifugation 3 000
      r/min for 5 min and preserved at -70 degrees Celsius in a freezer. Serum levels
      of corticosterone, cortisol, adrenocorticotrophic hormone (ACTH), cyclic
      adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), free
      triiodothyronine (FT3), free thyroxine (FT4), throtropic stimulation hormone,
      interleukin 1beta (IL-1beta) and interleukin 2 (IL-2) were detected by double
      antibody sandwich ELISA; cAMP/cGMP ratio was calculated, and the difference
      between the two constitutions in terms of these indexes was analyzed. RESULTS:
      Serum FT3 was 4.16 + or - 1.38 pmol/L in subjects with YDC, which was higher than
      that in subjects with GC (3.71 + or - 0.55 pmol/L), but levels of cortisol
      (124.58 + or - 45.36 ng/mL), ACTH (58.92 + or - 14.55 pg/mL), cGMP (66.00 + or -
      18.02 pmol/mL) and FT4 (12.33 + or - 3.12 pmol/L) in YDC were lower than those in
      GC (13.43 + or - 2.31 pmol/L), showing significant difference (P<0.05).
      CONCLUSION: YDC is related to some extent with the disturbances in the
      hypothalamus-pituitary-adrenal axis, hypothalamus-pituitary-thyroid axis, cyclic
      nucleoside system and immune function.

PMID- 20131034
TI  - Gene expression profiling of the proliferative effect of periplocin on mouse
      cardiac microvascular endothelial cells.
AB  - OBJECTIVE: Periplocin is an active digitalis-like component from Cortex
      Periplocae, which has been widely used in the treatment of heart diseases in
      China for many years. According to the recommendations on the cardiovascular
      effect of periplocin from in vivo experiments, subsequent in vitro experiments
      are greatly needed for the global assessment of periplocin. The objective of this
      study is to investigate the cell proliferation effect and the mechanism of
      periplocin on endothelial cells. METHODS: The proliferative activity of
      periplocin (0.4, 2, 10, 50, 250 micromol/L; 6, 12, 24, 48, 72 h) was investigated
      by a comparison with the well-reported cardiac glycoside, ouabain, on mouse
      cardiac microvascular endothelial cells (CMEC). 3-(4,5-dimethylthiazolyl)-2,5
      diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) and 5-bromo-2
      deoxyuridine (BrdU) assays were used to evaluate cell proliferation and
      viability. Subsequently, cDNA microarray experiments were performed on periplocin
      (50 micromol/L) and ouabain- (50 micromol/L) treated cells, and data was
      analyzed by ArrayTrack software. RESULTS: Periplocin could increase cell
      viability to a level lower than ouabain in the MTT analysis, but decrease LDH
      release simultaneously. The BrdU incorporation assay showed an increase in cell
      proliferation with 2-50 micromol/L periplocin. Genes related to protein
      serine/threonine kinase were the most significantly enriched in the 160 genes
      identified in periplocin versus the control. In the 165 genes regulated by
      periplocin versus ouabain, GTP-binding was the most altered term. CONCLUSIONS:
      The results demonstrated the proliferation action of periplocin on CMEC.
      Meanwhile, its lower cytotoxicity compared to ouabain provides a new insight into
      the treatment of heart failure.

PMID- 20131036
TI  - The effect of Xuefu Zhuyu Decoction on in vitro endothelial progenitor cell tube
      formation.
AB  - OBJECTIVE: To observe the effect of Xuefu Zhuyu Decoction ()-containing serum
      (XFZYD-CS) on endothelial progenitor cell (EPC) tube formation in vitro. METHODS:
      Mononuclear cells from rat bone marrow were prepared in a Ficoll density gradient
      centrifuge. EPCs were separated by the differential attachment method, and
      observed with inverted microscope for the effect of XFZYD-CS on EPC tube
      formation. RESULTS: After one day, EPCs exposed to the serum containing 5%, 10%
      and 15% XFZYD-CS formed typical tubes or vessel networks. The tube formation time
      was two days ahead of the control group and the size of most tubes in the serum
      groups was smaller than in the control group. CONCLUSION: XFZYD-CS could induce
      EPC angiogenesis and hasten tube formation, especially in capillary vessels. The
      study provides experimental evidence for the plausibility of Xuefu Zhuyu
      Decoction in the treatment of ischemic diseases.

PMID- 20131035
TI  - Endoplasmic reticulum stress induced by tunicamycin and antagonistic effect of
      Tiantai No.1 (1) on mesenchymal stem cells.
AB  - OBJECTIVE: Changes of the internal and external cellular environments can induce
      calcium homeostasis disorder and unfolded protein aggregation in the endoplasmic
      reticulum (ER). This ER function disorder is called endoplasmic reticulum stress
      (ERS). Severe long-term ERS can trigger the ER apoptosis signaling pathway,
      resulting in cell apoptosis and organism injury. Recent researches revealed that
      ERS-induced cell death was involved in the neurocyte retrogradation in the
      progress of neuron degenerative diseases, such as Alzheimer's disease (AD),
      Parkinson's disease and so on. Therefore, the protection effect of the
      traditional Chinese drug-Tiantai No. 1 (1) on the ERS injury of AD was
      investigated at the molecular gene level in this study with a view to explore the
      gene pharmacodynamic actions and mechanisms of this drug. METHODS: Primarily
      cultured marrow mesenchymal stem cells (MSCs) of rats were treated by tunicamycin
      (TM) in order to induce ERS. RT-PCR, fluorescence immunocytochemistry and Western
      blot techniques were used to determine the mRNA and protein expression levels of
      the protective stress protein-ER molecular chaperones GRP78 and GRP94 (which
      would assist cells to resist cellular stress injury), and to determine the mRNA
      and protein expression levels of apoptosis promoting molecule Caspase-12 on the
      membrane of the ER, respectively. RESULTS: Protein expression levels of GRP78 and
      GRP94 were significantly increased in the TM-induced MSCs, and the mRNA level of
      Caspase-12 was also remarkably increased in the TM-induced MSCs (P<0.05). All
      these proved that the ERS model was successfully established by TM in MSC.
      Meanwhile, the mRNA and protein levels of GRP78 and GRP94 were all significantly
      increased compared with the model group (P<0.05 or P<0.01) after MSCs were
      treated with Tiantai No.1 while the mRNA and protein expression levels of Caspase
      12 were significantly decreased compared with the model group (P<0.05 or P<0.01).
      This effect showed a dose dependent manner. CONCLUSION: Tiantai No.1 might
      attenuate the cell apoptosis induced by ERS injury, and thus protect the neurons
      against AD.

PMID- 20131037
TI  - Comfortable lifestyle-induced imbalance of neuro-endocrine-immunity network: a
      possible mechanism of vascular endothelial dysfunction.
AB  - OBJECTIVE: To observe the changes of vascular endothelial functions and general
      neuro-endocrine-immunity (NEI) network under the state of qi-deficiency syndrome
      induced by excessive idleness and to approach their internal relevance and
      illuminate initially the pathophysiological mechanism of vascular lesion induced
      by excessive idleness. METHODS: A total of 100 male Wistar rats were randomly
      divided into the control group and the qi-deficiency syndrome model group, 50
      rats in each group. The qi-deficiency syndrome model was established by feeding
      the animals with hyper-alimentation diet in combination with restricting movement
      for 10 weeks. Changes of common chemical signal molecules related to NEI and
      vascular endothelial functions were measured by the end of the experiment.
      Furthermore, their internal relevance was analyzed by the method of canonical
      correlation analysis. RESULTS: The vascular endothelial structure and function
      were obviously injured in the model group. Compared with the control group, the
      chemical signal molecules, such as 5-hydroxytryptamine (5-HT), corticosterone
      (CORT), triiodothyronine (T3), tetraiodothyronine (T4), angiotensin II (Ang II),
      interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in peripheral
      blood of the model group (n=43) were changed significantly (P<0.05 or P<0.01).
      Canonical correlation analysis showed that vascular endothelial dysfunction was
      correlated to the changes of these signal molecules in the NEI network.
      CONCLUSIONS: Comfort-based lifestyle induced not only vascular endothelial
      dysfunction but also an imbalance of the NEI network. Vascular endothelial
      dysfunction and the imbalanced NEI network interacted with each other, and an
      imbalance of the NEI network may be the pathophysiologic basis for the genesis
      and development of vascular endothelial dysfunction, even diseases of the blood
      vessel.

PMID- 20131038
TI  - Effects of Xinjining extract on inward rectifier potassium current in ventricular
      myocytes of guinea pig.
AB  - OBJECTIVE: To study the effect of Xinjining extract (, XJN) on inward rectifier
      potassium current (I(K1)) in ventricular myocyte (VMC) of guinea pigs and its
      anti-arrhythmic mechanism on ion channel level. METHODS: Single VMC was
      enzymatically isolated by zymolisis, and whole-cell patch clamp recording
      technique was used to record the I(k1) in VMC irrigated with XJN of different
      concentrations (1.25, 2.50, 5.00 g/L; six samples for each). The stable current
      and conductance of the inward component of I(K1) as well as the outward component
      of peak I(K1) and conductance of it accordingly was recorded when the test
      voltage was set on -110 mV. RESULTS: The suppressive rate of XJN on the inward
      component of I(K1) was 9.54% + or - 5.81%, 34.82% + or - 15.03%, and 59.52% + or 
      25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that
      for the outward component of peak I(K1) was 23.94% + or - 7.45%, 52.98% + or -
      19.62%, and 71.42% + or - 23.01%, respectively (all P<0.05). Moreover, different
      concentrations of XJN also showed effects for reducing I(K1) conductance.
      CONCLUSION: XJN has inhibitory effect on I(K1) in guinea pig's VMC, and that of
      the same concentration shows stronger inhibition on outward component than on
      inward component, which may be one of the mechanisms of its anti-arrhythmic
      effect.

PMID- 20131039
TI  - Effect of Gan-Pi regulatory needling in treating chloasma.
AB  - OBJECTIVE: To study the effect of Gan-Pi regulatory needling (GPRN) in treating
      chloasma and its influences on female sex hormones, superoxide dismutase (SOD),
      lipid peroxide (LPO) and melanocyte-stimulating hormone (MSH). METHODS: Ninety
      chloasma patients were equally randomized to three groups, the treatment group
      treated with GPRN, the control group treated with conventional Western medicine
      and the blank group untreated. Changes in the scores of skin lesion (area and
      color) and symptom, as well as blood levels of female sex hormones, MSH, SOD and
      LPO were observed and compared after 3 months of treatment. RESULTS: In the
      treatment group, the scores of skin lesion area and color were reduced from 2.76
      + or - 0.96 and 2.48 + or - 0.78 before treatment to 1.42 + or - 0.42 and 1.03 +
      or - 0.41 after treatment, respectively, while in the control group they were
      from 2.78 + or - 1.06 and 2.53 + or - 0.88 to 1.58 + or - 1.23 and 1.28 + or -
      0.96, respectively, all showing significant changes (P<0.05); the scores were
      insignificantly changed in the blank group (P>0.05). At the same time, the score
      of symptoms in the treatment group significantly improved after treatment
      (P<0.05), significantly different from that of the other two groups. Comparison
      of female sex hormones among groups showed no significant differences either
      before or after treatment. The level of LPO decreased and SOD increased in both
      the treatment group and the control group significantly (all P<0.05), but
      significant lowering of MSH was only seen in the treatment group (P<0.05).
      CONCLUSIONS: GPRN can effectively lessen the size and lighten the color of
      chloasma, improve the accompanying symptoms in patients and decrease LPO and MSH
      levels and increase the SOD level, but will not affect the level of the female
      sex hormones.

PMID- 20131040
TI  - Clinical efficacy of acupuncture on the morphine-related side effects in patients
      undergoing spinal-epidural anesthesia and analgesia.
AB  - OBJECTIVE: To investigate the effects of acupuncture on the morphine-related side
      effects (nausea, vomiting, itchiness and gastrointestinal disorders) in patients
      undergoing anesthesia and analgesia and try to find the clinical mechanism of
      acupuncture. METHODS: Patients scheduled to have transurethral prostatic
      resection: enrolled in the study (69 patients), characterized as Grade II or III
      by the American Society of Anesthesiologists physical status classification, were
      randomly assigned to three groups, 23 patients in each group: the placebo group
      (control group), non-anesthesia area (NAA) group, and the anesthesia area (AA)
      group. After spinal anesthesia, all patients received Patients Controlled
      Epidural Analgesia. The vital signs, bowel sounds, visual analogue scales,
      itchiness, nausea and vomiting, and time for first exhaust post operation were
      observed. RESULTS: Altogether, nine cases were eliminated, three in each group.
      Finally, sixty cases completed this study,: twenty in each group. There was a
      significant decrease of bowel sounds after morphine spinal anesthesia in the
      three groups. Compared with the control or AA group, the bowel sound recovered
      after acupuncture, the incidences of nausea and vomiting, itchiness, and time for
      first exhaust after operation decreased in the NAA group (P<0.05). There was a
      significant decrease of the incidence for itchiness in the NAA group compared
      with <the control group (P<0.05). CONCLUSIONS: On the basis of this study, it is
      obviously seen that acupuncture could: decrease the incidence of morphine-related
      side effects (nausea and vomiting, itchiness and gastrointestinal disorders) when
      the spinal cord conduct is normal. However, it decreases only the incidence of
      itchiness but not for gastrointestinal dysfunction when the spinal cord is
      blocked.

PMID- 20131041
TI  - Thinking on how to construct the system of Chinese medicine efficacy evaluation
      for coronary heart disease angina pectoris.
AB  - The existing efficacy evaluation for coronary heart disease (CHD) angina pectoris
      does not demonstrate the characteristics and advantages of Chinese medicine (CM),
      so a new system of efficacy evaluation which can scientifically and
      systematically reflect the specific features of CM needs to be urgently set up.
      Based on wide references of efficacy evaluations of CHD angina pectoris from our
      country and abroad, and considering the general acceptance by academic circles
      and demonstration of the characteristics of CM, this paper tries to set up a new
      index system of efficacy evaluation, combining both disease and syndrome
      differentiation for CHD angina pectoris. This paper also offers some explorations
      based on the results of clinical trials. The system is composed of six aspects,
      including efficacy evaluation of "disease", syndrome factors and main endpoints
      (the incidence of important clinical events), as well as patient reported
      outcomes, safety evaluation and medical economics.

PMID- 20131042
TI  - Current state of clinical diagnosis and treatment of infantile cytomegaloviral
      hepatitis.
AB  - Cytomegaloviral hepatitis is an infantile liver disease commonly encountered in
      China, which could be differentiated into 4 patterns with different clinical
      conditions. Along with the progress of laboratory diagnostic techniques, multiple
      diagnostic approaches are available for this disease, but accurate diagnosis can
      only be made when individual patients' realities are taken into consideration.
      Clinical treatments are various, and the Western medicine used is mainly anti
      viral agents such as Ganciclovir, and so far no unified therapeutic program has
      been formed. More and more ways of regarding Chinese medicine treatment of
      cytomegaloviral hepatitis have been published increasingly in recent years,
      though further research to seek preferable treatment programs is still expected.

PMID- 20131043
TI  - Is rs34861192 or rs1862513 a more promising variant for determining plasma
      resistin in an aged Japanese population?

PMID- 20131044
TI  - Effect of vitamin A treatment on superoxide dismutase-deficient yeast strains.
AB  - Vitamin A (Vit A) is widely suggested to be protective against oxidative stress.
      However, different studies have been demonstrated the pro-oxidant effects of
      retinoids in several experimental models. In this work, we used the yeast
      Saccharomyces cerevisiae as a model organism to study the Vit A effects on
      superoxide dismutase (SOD)-deficient yeast strains. We report here that Vit A
      (10, 20 and 40 mg/ml) decreases the survival of exponentially growing yeast
      cells, especially in strains deficient in CuZnSOD (sod1Delta) and CuZnSOD/MnSOD
      (sod1Deltasod2Delta). We also observed the protective effect of vitamin E against
      the Vit A-induced toxicity. Possible adaptation effects induced by sub-lethal
      oxidative stress were monitored by pre-, co- and post-treatment with the
      oxidative agent paraquat. The enzymatic activities of catalase (CAT) and
      glutathione peroxidase (GPx), and the total glutathione content were determined
      after Vit A treatment. Our results showed that CuZnSOD represents an important
      defence against Vit A-generated oxidative damage. In SOD-deficient strains, the
      main defence against Vit A-produced reactive oxygen species (ROS) is GPx.
      However, the induction of GPx activity is not sufficient to prevent the Vit A
      induced cell death in these mutants in exponential phase growth.

PMID- 20131045
TI  - Control of secondary metabolism by farX, which is involved in the gamma
      butyrolactone biosynthesis of Streptomyces lavendulae FRI-5.
AB  - The gamma-butyrolactone signaling system is distributed widely among
      streptomycetes as an important regulatory mechanism of antibiotic production
      and/or morphological differentiation. IM-2 [(2R,3R,1'R)-2-(1'-hydroxybutyl)-3
      hydroxymethyl-gamma-butanolide] is a gamma-butyrolactone that switches off the
      production of D: -cycloserine but switches on the production of several
      nucleoside antibiotics as well as blue pigment in Streptomyces lavendulae FRI-5.
      farX is a member of the afsA-family genes, which are proposed to encode enzymes
      involved in gamma-butyrolactone biosynthesis. Disruption of farX caused
      overproduction of D: -cycloserine, and abolished production of nucleoside
      antibiotic and blue pigment with the loss of IM-2 production. The finding that
      all phenotypic changes observed in the farX disruptant were restored by the
      addition of exogenous IM-2 suggested that FarX plays a biosynthetic role in IM-2
      production. Transcriptional comparison between the wild-type strain and the farX
      disruptant revealed that, in addition to already known genes farR1 and farR2,
      several other genes (farR4, farD, and farE) are under the transcriptional
      regulation of IM-2. Furthermore, the fact that farX transcription is under the
      control of IM-2 suggested that S. lavendulae FRI-5 has a fine-tuning system to
      control gamma-butyrolactone production.

PMID- 20131046
TI  - Differential human brain activation by vertical and horizontal global visual
      textures.
AB  - Mid-level visual processes which integrate local orientation information for the
      detection of global structure can be investigated using global form stimuli of
      varying complexity. Several lines of evidence suggest that the identification of
      concentric and parallel organisations relies on different underlying neural
      substrates. The current study measured brain activation by concentric, horizontal
      parallel, and vertical parallel arrays of short line segments, compared to arrays
      of randomly oriented segments. Six subjects were scanned in a blocked design
      functional magnetic resonance imaging experiment. We compared percentage BOLD
      signal change during the concentric, horizontal and vertical blocks within early
      retinotopic areas, the fusiform face area and the lateral occipital complex.
      Unexpectedly, we found that vertical and horizontal parallel forms differentially
      activated visual cortical areas beyond V1, but in general, activations to
      concentric and parallel forms did not differ. Vertical patterns produced the
      highest percentage signal change overall and only area V3A showed a significant
      difference between concentric and parallel (horizontal) stimuli, with the former
      better activating this area. These data suggest that the difference in brain
      activation to vertical and horizontal forms arises at intermediate or global
      levels of visual representation since the differential activity was found in mid
      level retinotopic areas V2 and V3 but not in V1. This may explain why earlier
      studies--using methods that emphasised responses to local orientation--did not
      discover this vertical-horizontal anisotropy.

PMID- 20131047
TI  - Early CT signs of progressive hemorrhagic injury following acute traumatic brain
      injury.
AB  - INTRODUCTION: Since progressive hemorrhagic injury (PHI) was introduced in
      neurosurgical literatures, several studies have been performed, the results of
      which have influenced doctors but do not define guidelines for the best treatment
      of PHI. PHI may be confirmed by a serial computerized tomography (CT) scan, and
      it has been shown to be associated with a fivefold increase in the risk of
      clinical worsening and is a significant cause of morbidity and mortality as well.
      So, early detection of PHI is practically important in a clinical situation.
      METHODS: To analyze the early CT signs of progressive hemorrhagic injury
      following acute traumatic brain injury (TBI) and explore their clinical
      significances, PHI was confirmed by comparing the first and repeated CT scans.
      Data were analyzed and compared including times from injury to the first CT and
      signs of the early CT scan. Logistic regression analysis was used to show the
      risk factors related to PHI. RESULTS: A cohort of 630 TBI patients was evaluated,
      and there were 189 (30%) patients who suffered from PHI. For patients with their
      first CT scan obtained as early as 2 h post-injury, there were 116 (77.25%) cases
      who suffered from PHI. The differences between PHIs and non-PHIs were significant
      in the initial CT scans showing fracture, subarachnoid hemorrhage (SAH), brain
      contusion, epidural hematoma (EDH), subdural hematoma (SDH), and multiple
      hematoma as well as the times from injury to the first CT scan (P < 0.01).
      Logistic regression analysis showed that early CT scans (EDH, SDH, SAH, fracture,
      and brain contusion) were predictors of PHI (P < 0.01). CONCLUSION: For patients
      with the first CT scan obtained as early as 2 h post-injury, a follow-up CT scan
      should be performed promptly. If the initial CT scan shows SAH, brain contusion,
      and primary hematoma with brain swelling, an earlier and dynamic CT scan should
      be performed for detection of PHI as early as possible and the medical
      intervention would be enforced in time.

PMID- 20131048
TI  - Extensive DRB region diversity in cynomolgus macaques: recombination as a driving
      force.
AB  - The DR region of primate species is generally complex and displays diversity
      concerning the number and combination of distinct types of DRB genes present per
      region configuration. A highly variable short tandem repeat (STR) present in
      intron 2 of nearly all primate DRB genes can be utilized as a quick and accurate
      high through-put typing procedure. This approach resulted previously in the
      description of unique and haplotype-specific DRB-STR length patterns in humans,
      chimpanzees, and rhesus macaques. For the present study, a cohort of 230
      cynomolgus monkeys, including self-sustaining breeding groups, has been examined.
      MtDNA analysis showed that most animals originated from the Indonesian islands,
      but some are derived from the mainland, south and north of the Isthmus of Kra.
      Haplotyping and subsequent sequencing resulted in the detection of 118 alleles,
      including 28 unreported ones. A total of 49 Mafa-DRB region configurations were
      detected, of which 28 have not yet been described. Humans and chimpanzees possess
      a low number of different DRB region configurations in concert with a high degree
      of allelic variation. In contrast, however, allelic heterogeneity within a given
      Mafa-DRB configuration is even less frequently observed than in rhesus macaques.
      Several of these region configurations appear to have been generated by
      recombination-like events, most probably propagated by a retroviral element
      mapping within DRB6 pseudogenes, which are present on the majority of haplotypes.
      This undocumented high level of DRB region configuration-associated diversity
      most likely represents a species-specific strategy to cope with various
      pathogens.

PMID- 20131051
TI  - Projecting land-use change and its consequences for biodiversity in northern
      Thailand.
AB  - Rapid deforestation has occurred in northern Thailand over the last few decades
      and it is expected to continue. The government has implemented conservation
      policies aimed at maintaining forest cover of 50% or more and promoting
      agribusiness, forestry, and tourism development in the region. The goal of this
      paper was to analyze the likely effects of various directions of development on
      the region. Specific objectives were (1) to forecast land-use change and land-use
      patterns across the region based on three scenarios, (2) to analyze the
      consequences for biodiversity, and (3) to identify areas most susceptible to
      future deforestation and high biodiversity loss. The study combined a dynamic
      land-use change model (Dyna-CLUE) with a model for biodiversity assessment
      (GLOBIO3). The Dyna-CLUE model was used to determine the spatial patterns of land
      use change for the three scenarios. The methodology developed for the Global
      Biodiversity Assessment Model framework (GLOBIO 3) was used to estimate
      biodiversity intactness expressed as the remaining relative mean species
      abundance (MSA) of the original species relative to their abundance in the
      primary vegetation. The results revealed that forest cover in 2050 would mainly
      persist in the west and upper north of the region, which is rugged and not easily
      accessible. In contrast, the highest deforestation was expected to occur in the
      lower north. MSA values decreased from 0.52 in 2002 to 0.45, 0.46, and 0.48,
      respectively, for the three scenarios in 2050. In addition, the estimated area
      with a high threat to biodiversity (an MSA decrease >0.5) derived from the
      simulated land-use maps in 2050 was approximately 2.8% of the region for the
      trend scenario. In contrast, the high-threat areas covered 1.6 and 0.3% of the
      region for the integrated-management and conservation-oriented scenarios,
      respectively. Based on the model outcomes, conservation measures were recommended
      to minimize the impacts of deforestation on biodiversity. The model results
      indicated that only establishing a fixed percentage of forest was not efficient
      in conserving biodiversity. Measures aimed at the conservation of locations with
      high biodiversity values, limited fragmentation, and careful consideration of
      road expansion in pristine forest areas may be more efficient to achieve
      biodiversity conservation.

PMID- 20131052
TI  - Spatial variability of groundwater depth and quality parameters in the National
      Capital Territory of Delhi.
AB  - The groundwater quantity and quality scenario is of much concern in the National
      Capital Territory of Delhi, India, which necessitates an investigation to
      envisage the extent of spatial variability of groundwater depth and pollutant
      concentration levels in this region. Therefore, in this study, an effort was made
      to generate the spatial variability map of groundwater depth and quality
      parameters (viz. chloride, electrical conductivity, fluoride, magnesium, and
      nitrate). Ordinary kriging was used to analyze the spatial variability of
      groundwater depth and quality parameters, whereas indicator kriging was used to
      analyze groundwater quality parameters equal to or greater than the pollution
      threshold values. It was observed that the semivariogram parameters fitted well
      in the exponential model for water depth and in the spherical model for water
      quality parameters. The generated spatial variability maps indicated that in 43%
      of the study area, groundwater depth was within 20 m. The salinity level was
      higher than 2.5 dS m(-1) in 69% of the study area and the nitrate concentration
      exceeded 45 mg l(-1) in 36% of the area. The probability maps showed that about
      24% of the area had the highest probability (0.8-1.0) of exceedence of the
      threshold electrical conductivity value and an area of 2% exhibited the highest
      probability of exceedence of the threshold value of nitrate concentration in the
      groundwater. The generated spatial variability and probability maps will assist
      water resource managers and policymakers in development of guidelines in
      judicious management of groundwater resources for agricultural and drinking
      purposes in the study area.

PMID- 20131053
TI  - Three-dimensional reconstruction of the superior mediastinum from Chinese Visible
      Human Female.
AB  - PURPOSE: This research aimed to construct three-dimensional (3D) visible models
      of the superior mediastinum for anatomic study and surgical approaches to the
      superior mediastinum. METHOD: Sectional images of the superior mediastinum were
      acquired through the Chinese Visible Human Female (VCHF) database. One hundred
      eighty images of the superior mediastinum were imported into Photoshop CS and the
      images were converted into a JPEG format. Surface and volume reconstruction were
      performed by 3D Doctor 3.5 and Amira 4.0 software programs on an ordinary
      personal computer, respectively. RESULT: The surface and volume reconstruction of
      the superior mediastinum were successful. The surface reconstruction model
      allowed rotation and magnification of the superior mediastinum structures as well
      as displayed the contours of reconstructed structures individually or as a
      composite with any other selected structure. Volume reconstruction displayed
      abundant internal detail of reconstructed images in transverse, coronal,
      sagittal, and random oblique sections. CONCLUSION: Three-dimensional, visible
      models of the superior mediastinum based on the sectional images of VCHF can
      provide unique insight into the anatomy of superior mediastinum. These models
      provide an excellent adjunct to the anatomy curriculum in medical schools and an
      invaluable tool for the practicing surgeon planning an operation in this complex
      anatomic region.

PMID- 20131055
TI  - Value of MR imaging in the differentiation of benign and malignant orbital tumors
      in adults.
AB  - PURPOSE: To prospectively evaluate magnetic resonance (MR) imaging including
      dynamic contrast-enhanced MR imaging in the differentiation of benign from
      malignant orbital masses and to evaluate which MR imaging features are most
      predictive of malignant tumors. MATERIALS AND METHODS: The study was approved by
      the institutional review board and signed informed consent was obtained.
      Nonenhanced, static, and dynamic contrast-enhanced MR imaging was performed in
      102 adult patients with an orbital mass. Diagnosis was based on histologic
      findings. MR imaging features of benign and malignant orbital lesions were
      evaluated correlated with histological findings. Multivariate logistic regression
      analysis was employed to identify the best combination of MR imaging features
      that might be predictive of malignancy. RESULTS: Nonenhanced, static, and dynamic
      enhancement MR imaging was significantly superior to two other models in
      prediction of malignancy (p < 0.05). Multivariate logistic regression analysis
      identified that the most discriminating MR imaging features were isointense mass
      on T2-weighted imaging and a washout-type time-intensity curve for both
      observers. CONCLUSION: Nonenhanced, static, and dynamic enhancement MR imaging
      improved differentiation between benign and malignant orbital masses in adult
      patients.

PMID- 20131056
TI  - Temporal properties of the lens eyes of the box jellyfish Tripedalia cystophora.
AB  - Box jellyfish (Cubomedusae) are visually orientating animals which possess a
      total of 24 eyes of 4 morphological types; 2 pigment cup eyes (pit eye and slit
      eye) and 2 lens eyes [upper lens-eye (ule) and lower lens-eye (lle)]. In this
      study, we use electroretinograms (ERGs) to explore temporal properties of the two
      lens eyes. We find that the ERG of both lens eyes are complex and using
      sinusoidal flicker stimuli we find that both lens eyes have slow temporal
      resolution. The average flicker fusion frequency (FFF) was found to be
      approximately 10 Hz for the ule and 8 Hz for the lle. Differences in the FFF and
      response patterns between the two lens eyes suggest that the ule and lle filter
      information differently in the temporal domain and thus are tuned to perform
      different visual tasks. The data collected in this study support the idea that
      the visual system of box jellyfish is a collection of special purpose eyes.

PMID- 20131057
TI  - Synchronization of wing beat cycle of the desert locust, Schistocerca gregaria,
      by periodic light flashes.
AB  - Studies on the generation of rhythmic motor patterns have shown that peripheral
      sensory input may contribute substantially to the rhythm generating network. A
      prominent example is the wing beat frequency of desert locusts, which can be
      entrained to rhythmic mechanosensory input, but also to the frequency of periodic
      light flashes. To further analyze the entrainment by light, tethered flying
      locusts were presented with periodic light flashes, while the position of the
      forewing was filmed. We show that entrainment of wing beat occurs both in the UV
      and green range of light. Animals maintained a characteristic phase relationship
      to the light stimulus with the most elevated wing position occurring at the end
      of the dark phase. Speed and time course of entrainment varied greatly and ranged
      from the duration of a single wing beat cycle to several seconds. To identify the
      visual system mediating entrainment, synchronization to UV light was tested after
      cutting the optic stalks to the optic lobes/compound eyes or the ocellar nerves.
      The results show that light entrainment of the locust flight pattern is largely
      and perhaps exclusively mediated via the fast ocellar pathway and may have a role
      to stabilize flight with respect to the horizon.

PMID- 20131059
TI  - Rapid and sensitive assessment of the IDH1 and IDH2 mutation status in cerebral
      gliomas based on DNA pyrosequencing.
AB  - Diffusely infiltrating cerebral gliomas frequently carry point mutations in codon
      132 of the isocitrate dehydrogenase 1 (IDH1) gene or in codon 172 of the IDH2
      gene, which are both clinically important as diagnostic and prognostic markers.
      Here, we report on a method that allows for the rapid detection of IDH1 and IDH2
      mutations based on pyrosequencing. The method is applicable to routinely
      processed tissue specimens and provides quantitative mutation data within less
      than one working day. Due to its high sensitivity, the technique may also be used
      for the diagnostic assessment of IDH1 or IDH2 mutation in tissue samples with low
      tumor cell content, such as the infiltration zone of diffuse gliomas. Using
      pyrosequencing and/or conventional cycle sequencing of IDH1 and IDH2 in 262
      gliomas, we confirm frequent mutations in diffuse astrocytic and oligodendroglial
      gliomas, corroborate a prognostic role for IDH1 mutation in primary glioblastomas
      and show that pleomorphic xanthoastrocytomas generally lack mutations in these
      genes.

PMID- 20131060
TI  - Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by
      activated Wnt-signalling.
AB  - Activating beta-catenin mutations with aberrant cytoplasmic and nuclear protein
      accumulation are hallmarks of adamantinomatous craniopharyngiomas (adaCP). These
      tumours tend to be associated with unfavourable and occasionally disastrous
      sequelae, as they invade adjacent brain structures such as the hypothalamus. The
      peculiar digitate growth pattern does not always allow gross surgical removal
      often leading to recurrence. The tips of invading adaCP epithelium harbour cell
      clusters with nuclear beta-catenin accumulations, suggesting an influence of beta
      catenin-dependent signal transduction on the tumour migratory capacity. This
      hypothesis was tested by suppressing beta-catenin expression in six primary human
      adaCP cell cultures using small interfering RNA (siRNA) directed against the beta
      catenin gene (CTNNB1). Tumour cell migration was significantly reduced in Boyden
      chamber and wound-healing experiments following siRNA treatment. We further
      showed that fascin, a target gene of beta-catenin TCF signalling in colorectal
      cancer cells and a key component of filopodia, is also involved in this process.
      beta-Catenin accumulating tumour cells co-express fascin and fascin mRNA levels
      can be significantly down-regulated in adaCP cultures treated with CTNNB1 siRNA.
      Furthermore, migration experiments showed a significantly lower cell motility of
      adaCP tumour cells in vitro when transfected with fascin siRNA. This suggests
      that activated Wnt-signalling serves as a promoter of the epithelial migration
      machinery by regulating target molecules such as fascin in adaCP tumour cells.

PMID- 20131061
TI  - Plutonium worker dosimetry.
AB  - Epidemiological studies of the relationship between risk and internal exposure to
      plutonium are clearly reliant on the dose estimates used. The International
      Commission on Radiological Protection (ICRP) is currently reviewing the latest
      scientific information available on biokinetic models and dosimetry, and it is
      likely that a number of changes to the existing models will be recommended. The
      effect of certain changes, particularly to the ICRP model of the respiratory
      tract, has been investigated for inhaled forms of (239)Pu and uncertainties have
      also been assessed. Notable effects of possible changes to respiratory tract
      model assumptions are (1) a reduction in the absorbed dose to target cells in the
      airways, if changes under consideration are made to the slow clearing fraction
      and (2) a doubling of absorbed dose to the alveolar region for insoluble forms,
      if evidence of longer retention times is taken into account. An important factor
      influencing doses for moderately soluble forms of (239)Pu is the extent of
      binding of dissolved plutonium to lung tissues and assumptions regarding the
      extent of binding in the airways. Uncertainty analyses have been performed with
      prior distributions chosen for application in epidemiological studies. The
      resulting distributions for dose per unit intake were lognormal with geometric
      standard deviations of 2.3 and 2.6 for nitrates and oxides, respectively. The
      wide ranges were due largely to consideration of results for a range of
      experimental data for the solubility of different forms of nitrate and oxides.
      The medians of these distributions were a factor of three times higher than
      calculated using current default ICRP parameter values. For nitrates, this was
      due to the assumption of a bound fraction, and for oxides due mainly to the
      assumption of slower alveolar clearance. This study highlights areas where more
      research is needed to reduce biokinetic uncertainties, including more accurate
      determination of particle transport rates and long-term dissolution for plutonium
      compounds, a re-evaluation of long-term binding of dissolved plutonium, and
      further consideration of modeling for plutonium absorbed to blood from the lungs.

PMID- 20131062
TI  - Muscle performance during isokinetic concentric and eccentric abduction in
      subjects with subacromial impingement syndrome.
AB  - Peak torque (PT), total work (TW) and acceleration time (AT) were measured during
      isokinetic concentric and eccentric abduction of the shoulder in subjects with
      subacromial impingement syndrome (SIS) and healthy subjects. The SIS group
      consisted of 27 subjects (33.48 +/- 9.94 years) with unilateral SIS and it was
      divided into two groups: (1) SIS with the dominant involved side, (2) SIS with
      the nondominant involved side. The control group consisted of 23 healthy subjects
      (32.26 +/- 9.04 years). PT, TW and AT were measured bilaterally at 60 and 180
      degrees /s. No significant interactions were found between group and side (P >
      0.05), as well as no significant main effects of group and side (P > 0.05) for
      all variables during concentric abduction of the shoulder at both tested speeds.
      During the eccentric contractions, lower TW (P < 0.05) was demonstrated by the
      nondominant uninvolved side of SIS group at 60 degrees /s, and by the uninvolved
      sides of the SIS groups at 180 degrees /s compared to the dominant side of the
      controls. At 180 degrees /s, the nondominant uninvolved side of the SIS group
      demonstrated slower AT (P < 0.05) compared to the dominant side of the control
      group, as well as the nondominant involved side of the SIS group compared to the
      nondominant side of the controls. The results showed no alterations in the
      measured parameters during concentric and eccentric phases of isokinetic
      abduction in subjects with SIS when compared to a control group. However,
      alterations may be observed in the contralateral side during the eccentric phase
      of abduction in subjects with unilateral conditions of SIS.

PMID- 20131063
TI  - The influence of muscle length on the fatigue-related reduction in joint range of
      motion of the human dorsiflexors.
AB  - The fatigue-related reduction in joint range of motion (ROM) during dynamic
      contraction tasks may be related to muscle length-dependent alterations in torque
      and contractile kinetics, but this has not been systematically explored
      previously. Twelve young men performed a repetitive voluntary muscle shortening
      contraction task of the dorsiflexors at a contraction load of 30% of maximum
      voluntary isometric contraction (MVC) torque, until total 40 degrees ROM had
      decreased by 50% at task failure (POST) to 20 degrees ROM. At both a short (5
      degrees dorsiflexion) and long muscle length (35 degrees plantar flexion joint
      angle relative to a 0 degrees neutral ankle joint position), voluntary
      activation, MVC torque, and evoked tibialis anterior contractile properties of a
      52.8 Hz high-frequency isometric tetanus [peak evoked torque, maximum rate of
      torque development (MRTD), maximum rate of relaxation (MRR)] were evaluated at
      baseline (PRE), at POST, and up to 10 min of recovery. At POST, we measured
      similar fatigue-related reductions in torque (voluntary and evoked) and slowing
      of contractile kinetics (MRTD and MRR) at both the short and long muscle lengths.
      Thus, the fatigue-related reduction in ROM could not be explained by length
      dependent fatigue. Although torque (voluntary and evoked) at both muscle lengths
      was depressed and remained blunted throughout the recovery period, this was not
      related to the rapid recovery of ROM at 0.5 min after task failure. The reduction
      in ROM, however, was strongly related to the reduction in joint angular velocity
      (R(2) = 0.80) during the fatiguing task, although additional factors cannot yet
      be overlooked.

PMID- 20131064
TI  - Plasma adipokine and inflammatory marker concentrations are altered in obese, as
      opposed to non-obese, type 2 diabetes patients.
AB  - Elevated plasma free fatty acid (FFA), inflammatory marker, and altered adipokine
      concentrations have been observed in obese type 2 diabetes patients. It remains
      unclear whether these altered plasma concentrations are related to the diabetic
      state or presence of obesity. In this cross-sectional observational study, we
      compare basal plasma FFA, inflammatory marker, and adipokine concentrations
      between obese and non-obese type 2 diabetes patients and healthy, non-obese
      controls. A total of 20 healthy, normoglycemic males (BMI <30 kg/m(2)), 20 non
      obese (BMI <30 kg/m(2)) and 20 obese (BMI >35 kg/m(2)) type 2 diabetes patients
      were selected to participate in this study. Groups were matched for age and
      habitual physical activity level. Body composition, glycemic control, and
      exercise performance capacity were assessed. Basal blood samples were collected
      to determine plasma leptin, adiponectin, resistin, tumor necrosis factor alpha
      (TNFalpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and
      FFA concentrations. Plasma FFA, inflammatory marker (hsCRP, IL-6, TNFalpha),
      adipokine (adiponectin, resistin, leptin), and triglyceride concentrations did
      not differ between non-obese diabetes patients and healthy, normoglycemic
      controls. Plasma FFA, IL-6, hsCRP, leptin, and triglyceride levels were
      significantly higher in the obese diabetes patients when compared with the
      healthy normoglycemic controls (P < 0.05). Furthermore, plasma hsCRP and leptin
      levels were significantly higher in the obese versus non-obese diabetes patients
      (P < 0.05). Significant correlations between plasma parameters and glycemic
      control were observed, but disappeared after adjusting for trunk adipose tissue
      mass. Elevated plasma leptin, hsCRP, IL-6, and FFA concentrations are associated
      with obesity and not necessarily with the type 2 diabetic state.

PMID- 20131065
TI  - One hundred years of Molecular Genetics and Genomics: 100 years of extra-nuclear
      inheritance.

PMID- 20131066
TI  - Characterization of expressed sequence tags (ESTs) of pigeonpea (Cajanus cajan
      L.) and functional validation of selected genes for abiotic stress tolerance in
      Arabidopsis thaliana.
AB  - Pigeonpea, a major grain legume crop with remarkable drought tolerance traits,
      has been used for the isolation of stress-responsive genes. Herein, we report
      generation of ESTs, transcript profiles of selected genes and validation of
      candidate genes obtained from the subtracted cDNA libraries of pigeonpea plants
      subjected to PEG/water-deficit stress conditions. Cluster analysis of 124
      selected ESTs yielded 75 high-quality ESTs. Homology searches disclosed that 55
      ESTs share significant similarity with the known/putative proteins or ESTs
      available in the databases. These ESTs were characterized and genes relevant to
      the specific physiological processes were identified. Of the 75 ESTs obtained
      from the cDNA libraries of drought-stressed plants, 20 ESTs proved to be unique
      to the pigeonpea. These sequences are envisaged to serve as a potential source of
      stress-inducible genes of the drought stress-response transcriptome, and hence
      may be used for deciphering the mechanism of drought tolerance of the pigeonpea.
      Expression profiles of selected genes revealed increased levels of m-RNA
      transcripts in pigeonpea plants subjected to different abiotic stresses.
      Transgenic Arabidopsis lines, expressing Cajanus cajan hybrid-proline-rich
      protein (CcHyPRP), C. cajan cyclophilin (CcCYP) and C. cajan cold and drought
      regulatory (CcCDR) genes, exhibited marked tolerance, increased plant biomass and
      enhanced photosynthetic rates under PEG/NaCl/cold/heat stress conditions. This
      study represents the first report dealing with the isolation of drought-specific
      ESTs, transcriptome analysis and functional validation of drought-responsive
      genes of the pigeonpea. These genes, as such, hold promise for engineering crop
      plants bestowed with tolerance to major abiotic stresses.

PMID- 20131067
TI  - AtfA bZIP-type transcription factor regulates oxidative and osmotic stress
      responses in Aspergillus nidulans.
AB  - The aim of the study was to demonstrate that the bZIP-type transcription factor
      AtfA regulates different types of stress responses in Aspergillus nidulans
      similarly to Atf1, the orthologous 'all-purpose' transcription factor of
      Schizosaccharomyces pombe. Heterologous expression of atfA in a S. pombe
      Deltaatf1 mutant restored the osmotic stress tolerance of fission yeast in
      surface cultures to the same level as recorded in complementation studies with
      the atf1 gene, and a partial complementation of the osmotic and oxidative-stress
      sensitive phenotypes was also achieved in submerged cultures. AtfA is therefore a
      true functional ortholog of fission yeast's Atf1. As demonstrated by RT-PCR
      experiments, elements of both oxidative (e.g. catalase B) and osmotic (e.g.
      glycerol-3-phosphate dehydrogenase B) stress defense systems were
      transcriptionally regulated by AtfA in a stress-type-specific manner. Deletion of
      atfA resulted in oxidative-stress-sensitive phenotypes while the high-osmolarity
      stress sensitivity of the fungus was not affected significantly. In A. nidulans,
      the glutathione/glutathione disulfide redox status of the cells as well as
      apoptotic cell death and autolysis seemed to be controlled by regulatory elements
      other than AtfA. In conclusion, the orchestrations of stress responses in the
      aspergilli and in fission yeast share several common features, but further
      studies are needed to answer the important question of whether a fission yeast
      like core environmental stress response also operates in the euascomycete genus
      Aspergillus.

PMID- 20131068
TI  - Linearization of the full activated sludge model No 1 for interaction analysis.
AB  - This paper deals with the linearization of the full activated sludge model No 1
      (ASM1) in the scope of interaction analysis. For consistency, the linearization
      procedure is developed and validated within the BSM1 simulation benchmark
      framework. It is based on reaction rate approximation by linear combinations of
      states. The linear rate models are identified and incorporated in the mass
      balance equations, yielding a linear locally equivalent to the ASM1 model. Linear
      models for anoxic and aerated compartments are proposed. It is observed that the
      presented models track very closely the nonlinear ASM1 responses to various
      influent data. The key feature of this linearization strategy is that the gotten
      linear version of the ASM1 model is linear time invariant (LTI) and that it
      conserves the states biological interpretation and the original ASM1 dimension.
      It allows, therefore, application of interaction analysis methods and makes it
      possible to determine motivated control configurations for the ASM1 model.

PMID- 20131069
TI  - Effects of a gastrin-releasing peptide receptor antagonist on D-amphetamine
      induced oxidative stress in the rat brain.
AB  - Previous studies have suggested that bipolar disorder may be associated with
      oxidative stress. Administration of D: -amphetamine (AMPH) has been put forward
      as an animal model of mania, and has shown to increase oxidative stress
      parameters in the rat brain. Thus, we have used the gastrin-releasing peptide
      receptor antagonist [D-Tpi(6)Leu(13)psi (CH(2)NH)-Leu(14)] bombesin (RC-3095) as
      a pharmacological tool to investigate the role of bombesin-like peptides in the
      redox balance in the hippocampus and cortex of rats treated with AMPH. Rats were
      given a single 10 ml/kg intraperitoneal (i.p.) injection of saline (SAL) or RC
      3095 (0.1, 1.0 or 10.0 mg/kg) followed by an i.p. injection of SAL or amphetamine
      (AMPH 2.0 mg/kg) 30 min later. Locomotor activity was evaluated 2 h after the
      last drug injection. The thiobarbituric acid reactive substances (TBARS), protein
      carbonyl formation, superoxide dismutase and catalase (CAT) activity were
      measured in hippocampus, striatum and cortex as markers of oxidative stress. The
      results show that RC-3095 blocks AMPH-induced hyperlocomotion. Moreover, specific
      doses of RC-3095 alone increased the levels of oxidative stress in the dorsal
      hippocampus and cortex. However, when AMPH was subsequently administrated, RC
      3095 decreased TBARS and protein carbonyls formation and increased the superoxide
      dismutase and CAT activity in the hippocampus, striatum and cortex. The effects
      of GRPR antagonist seemed to be region and dose specific. In conclusion, the
      results suggest that GRPR antagonists might display antioxidant properties in the
      brain.

PMID- 20131070
TI  - Effects of amantadine on circulating neurotransmitters in healthy subjects.
AB  - Considering that glutamatergic axons innervate the C1(Ad) medullary nuclei, which
      are responsible for the excitation of the peripheral adrenal glands, we decided
      to investigate catecholamines (noradrenaline, adrenaline and dopamine) plus
      indolamines (plasma serotonin and platelet serotonin) at the blood level, before
      and after a small oral dose of amantadine, a selective NMDA antagonist. We found
      that the drug provoked a selective enhancement of noradrenaline plus a
      minimization of adrenaline, dopamine, plasma serotonin and platelet serotonin
      circulating levels. Significant enhancement of diastolic blood pressure plus
      reduction of systolic blood pressure and heart rate paralleled the circulating
      parameter changes. The above findings allow us to postulate that the drug was
      able to enhance the peripheral neural sympathetic activity. Minimization of both
      adrenal sympathetic and parasympathetic activities was also registered after the
      amantadine challenge. The above findings supported the postulation that this drug
      should be a powerful therapeutic tool for treating diseases affected by adrenal
      sympathetic hyperactivity.

PMID- 20131071
TI  - Structural abnormalities in the substantia nigra and neighbouring nuclei in
      Tourette's syndrome.
AB  - Although midbrain nuclei (substantia nigra, ventral tegmental area, and
      periaqueductal grey) are considered candidate loci of pathology in Tourette's
      syndrome (TS), few imaging studies have examined midbrain structure. The
      objective of this study was to evaluate the presence of subtle structural
      abnormalities in the midbrain of patients with TS. High-field magnetic resonance
      imaging (MRI) (1.5- and 3-T) was used in 23 patients with TS and in 20 age- and
      sex-matched normal control subjects. Tics symptoms were rated using the Yale
      Global Tic Severity Scale and comorbid neuropsychiatric disorders were evaluated
      with standardised psychiatric rating scales. MRI scans revealed subtle structural
      abnormalities consistent with expanded perivascular spaces (EPVS) in the
      substantia nigra (compacta and reticulata) and neighbouring nuclei in 6 (26%)
      patients with TS, but in none of the normal control subjects (P = 0.045).
      Stereotyped movements were more frequent (P = 0.017) amongst TS patients with
      midbrain EPVS than in TS patients with normal MRI. Parkinsonism, posttraumatic
      stress disorder and autistic spectrum disorders exclusively occurred in TS
      patients with midbrain EPVS. There were no significant between-group differences
      in other comorbid neuropsychiatric disorders and in tics. Although EPVS are
      generally viewed as incidental findings, our results suggest that when EPVS are
      located in the midbrain they may be symptomatic. These abnormalities would reduce
      the actual number of neurons in specific midbrain nuclei (e.g., substantia nigra)
      and disrupt their connectivity with limbic, associative, and motor circuits.

PMID- 20131072
TI  - Response to zolendronic acid in children with type III osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a common genetic disorder that manifests with
      intrauterine or pre- or postnatal fractures, blue sclera, and deafness. Various
      treatments for the management of OI have been tried, of which bisphosphonates
      (BPs) seem to have the maximum benefit in reducing fracture rate and improving
      bone density. Zolendronic acid is a newer BP tried for several bone diseases,
      mainly in adults. The objective of our analysis was to study the response to
      zolendronic acid in children with type III OI. The case records of subjects with
      type III OI receiving zolendronic acid in the past 3 years between February 2006
      and March 2009 were analyzed. Relevant details were recorded on a predesigned
      chart. Subjective improvement, reduction in number of fractures, and the DEXA
      scan Z-score were used to judge improvement. Five OI type III cases were followed
      up in the Genetic clinic. Presentation was from neonatal period to 7 years of
      age; M:F ratio was 3:2. Average duration of therapy given was 20.4 months.
      Improvement was noted in all patients, in the form of reduction in frequency of
      fractures (P = 0.002) and increase in bone density on DEXA scan (P = 0.01). Side
      effects noted were flu-like symptoms and myalgia. No clinical problems due to
      hypocalcemia were noted in any of the patients. Thus, zolendronic acid is seen as
      a safe and effective BP in type III OI children. The exact dose for optimal
      benefit is yet to be determined. The long-term effects of newer BPs need further
      long-term trials.

PMID- 20131073
TI  - Efficacy of high intensity diode laser as an adjunct to non-surgical periodontal
      treatment: a randomized controlled trial.
AB  - The high intensity diode laser has been studied in periodontics for the reduction
      of subgingival bacteria in non-surgical treatment. Our study evaluated the
      bacterial effect as well as changes in periodontal clinical parameters promoted
      by root scaling and planing associated with this wavelength. Twenty-seven
      patients randomly assigned in two groups underwent root scaling and planing on
      the tested sites, and only the experimental group received the diode laser
      irradiation. Among the clinical parameters studied, the clinical probing depth
      (CPD) and the clinical attachment level (CAL) resulted in significant enhancement
      in the control group when compared with the experimental group (P = 0.014 and P =
      0.039, respectively). The results were similar for both groups regarding the
      plaque index (PI) and bleeding on probing (BP). No significant difference in the
      microbiological parameters was observed between the control and experimental
      groups. It was possible to conclude that the high power diode laser adjunct to
      the non-surgical periodontal treatment did not promote additional effects to the
      conventional periodontal treatment.

PMID- 20131074
TI  - Contrast detail phantom comparison on a commercially available unit. Digital
      breast tomosynthesis (DBT) versus full-field digital mammography (FFDM).
AB  - The performance of a commercial digital mammographic system working in 2D planar
      versus tomosynthesis mode was evaluated in terms of the image signal difference
      to noise ratio (SDNR). A contrast detail phantom was obtained embedding 1 cm
      Plexiglas, including 49 holes of different diameter and depth, between two layers
      containing a breast-simulating material. The phantom was exposed with the details
      plane perpendicular to the X-ray beam using the manufacturer's standard clinical
      breast acquisition parameters. SDNR in the digital breast tomosynthesis (DBT)
      images was higher than that of the full-field digital mammography (FFDM) for 38
      out of 49 details in complex background conditions. These differences (p < 0.05)
      are statistically significant for 19 details out of 38. The relative SDNR results
      for DBT and FFDM images showed a dependence on the diameter of the details
      considered. This paper proposes an initial framework for a global image quality
      evaluation for commercial systems that can operate with different image
      acquisition modality using the same detector.

PMID- 20131075
TI  - Comparison between procalcitonin and C-reactive protein for early diagnosis of
      children with sepsis or septic shock.
AB  - OBJECTIVE AND DESIGN: The objective of the paper is to examine the behavior of C
      reactive protein (CRP) and procalcitonin (PCT) in the first 12 h of admission and
      verify which performs better to differentiate children with septic conditions.
      SUBJECTS: Septic children aged between 28 days and 14 years were divided into
      sepsis (SG; n = 46) and septic shock (SSG; n = 41) groups. CRP and PCT were
      measured at admission (T0) and 12 h later (T12 h). PCT results were classed as:
      0.5 ng/ml = sepsis unlikely; >or=0.5 to <2 = sepsis possible; >or=2 to <10 =
      systemic inflammation; >or=10 = septic shock. RESULTS: At T0, there was a higher
      frequency of SSG with PCT >10 compared to SG [SSG: 30 (73.1%) > SG: 14 (30.4%); P
      < 0.05]. Similar results were observed at T12 h. Pediatric Risk of Mortality I
      score was significantly higher for SSG patients with higher PCT than SG patients.
      CRP levels were not statistically different for groups and time points.
      CONCLUSIONS: PCT was better than CRP for diagnosing sepsis and septic shock,
      mainly at admission, and is related to disease severity.

PMID- 20131077
TI  - Modulating the pharmacokinetics of therapeutic antibodies.
AB  - With the advent of antibody fragments and alternative binding scaffolds, that are
      devoid of Fc-regions, strategies to increase the half-life of small proteins are
      becoming increasingly important. Currently, the established method is chemical
      PEGylation, but more elaborate approaches are being described such as
      polysialylation, amino acid polymers and albumin-binding derivatives. This
      article reviews the main strategies for pharmacokinetic enhancement, primarily
      chemical conjugates and recombinant fusions that increase apparent molecular
      weight or hydrodynamic radius or interact with serum albumin which itself has a
      long plasma half-life. We highlight the key chemical linkage methods that
      preserve antibody function and retain stability and look forward to the next
      generation of technologies which promise to make better quality pharmaceuticals
      with lower side effects. Although restricted to antibodies, all of the approaches
      covered can be applied to other biotherapeutics.

PMID- 20131076
TI  - Role of mast cells, stem cell factor and protease-activated receptor-2 in
      tubulointerstitial lesions in IgA nephropathy.
AB  - BACKGROUND: To elucidate the role of mast cells (MCs) in the pathogenesis of
      tubulointerstitial lesions in IgA nephropathy (IgAN), we investigated the number
      of MCs, serum stem cell factor (SCF), protease-activated receptor-2 (PAR-2) and
      alpha-smooth-muscle actin (alpha-SMA) in the kidney and the correlation between
      MC number, SCF, PAR-2, alpha-SMA and tubulointerstitial lesions in biopsy
      specimens and serum creatinine levels, urinary protein excretion in patients with
      IgA nephropathy. METHODS: Thirty-five patients with IgA nephropathy were enrolled
      in this study. Clinical parameters, such as serum creatinine and urinary protein
      excretion, were obtained from each patient at the time of biopsy. Paraffin
      embedded sections were used for immunohistochemical staining. Monoclonal
      antibodies to human tryptase, alpha-SMA, and SCF and polyclonal antibody to PAR-2
      were used as primary antibodies. Ten cortical interstitial fields were randomly
      selected and assessed using a computer-assisted color image analyzer.
      Tubulointerstitial fibrosis was assessed as the percentage of the area stained
      with Masson trichrome in ten cortical interstitial fields. RESULTS: In all of the
      control subjects, few tryptase-positive MCs were observed in the glomeruli and
      interstitium. In contrast, sparse MCs were observed in the interstitium, but not
      in the glomeruli of diseased kidneys. The number of interstitial MCs in the
      tubulointerstitial lesions, the expression of SCF, PAR-2 and alpha-SMA were
      positively correlated with the degree of interstitial fibrosis. A close
      correlation between MCs, alpha-SMA, PAR-2 and SCF was found (r = 0.887 for alpha
      SMA, r = 0.844 for PAR-2, r = 0.853 for SCF, P < 0.01). Also a close correlation
      between alpha-SMA, PAR-2 and SCF was found (r = 0.874 for PAR-2, r = 0.862 for
      SCF, P < 0.01). PAR-2 was correlated with SCF (r = 0.893, P < 0.01). Moreover, a
      significant positive correlation was observed between the number of interstitial
      MCs, the expression of SCF, PAR-2 and alpha-SMA and the serum creatinine level (r
      = 0.738 for MCs, r = 0.658 for alpha-SMA, r = 0.692 for PAR-2, r = 0.754 for SCF,
      P < 0.05). CONCLUSIONS: Our findings suggest that MC infiltration possibly
      induced by SCF in renal interstitial tissues seems to be associated with
      tubulointerstitial fibrosis through PAR-2 in IgA nephropathy.

PMID- 20131078
TI  - Studies supporting the use of mechanical mixing in large scale beer
      fermentations.
AB  - Brewing fermentations have traditionally been undertaken without the use of
      mechanical agitation, with mixing being provided only by the fluid motion induced
      by the CO(2) evolved during the batch process. This approach has largely been
      maintained because of the belief in industry that rotating agitators would damage
      the yeast. Recent studies have questioned this view. At the bench scale, brewer's
      yeast is very robust and withstands intense mechanical agitation under aerobic
      conditions without observable damage as measured by flow cytometry and other
      parameters. Much less intense mechanical agitation also decreases batch
      fermentation time for anaerobic beer production by about 25% compared to mixing
      by CO(2) evolution alone with a small change in the concentration of the
      different flavour compounds. These changes probably arise for two reasons.
      Firstly, the agitation increases the relative velocity and the area of contact
      between the cells and the wort, thereby enhancing the rate of mass transfer to
      and from the cells. Secondly, the agitation eliminates spatial variations in both
      yeast concentration and temperature, thus ensuring that the cells are maintained
      close to the optimum temperature profile during the whole of the fermentation
      time. These bench scale studies have recently been supported by results at the
      commercial scale from mixing by an impeller or by a rotary jet head, giving more
      consistent production without changes in final flavour. It is suggested that this
      reluctance of the brewing industry to use (adequate) mechanical agitation is
      another example where the myth of shear damage has had a detrimental effect on
      the optimal operation of commercial bioprocessing.

PMID- 20131079
TI  - Construction of a direct starch-fermenting industrial strain of Saccharomyces
      cerevisiae producing glucoamylase, alpha-amylase and debranching enzyme.
AB  - To develop a strain of Saccharomyces cerevisiae that produces ethanol directly
      from starch, two integrative vectors were constructed to allow the simultaneous
      multiple integration of the Aspergillus awamori glucoamylase gene (GA1) and the
      Debaryomyces occidentalis alpha-amylase gene (AMY) and glucoamylase with
      debranching activity gene (GAM1) into the chromosomes of an industrial strain of
      S. cerevisiae. The GA1 and AMY genes were constitutively expressed under the ADC1
      promoter in S. cerevisiae using the double delta-integration system. The GAM1
      gene was constitutively expressed under the corresponding promoter using the
      double 18S rDNA-integration system. The recombinant industrial strain secreting
      biologically active alpha-amylase, glucoamylase and debranching enzyme was able
      to ferment starch to ethanol in a single step. The new strain produced 8% (v/v)
      ethanol (62.8 g l(-1)) from 20% (w/v) soluble starch after 2 days, fermentation.

PMID- 20131080
TI  - Regioselective carboxylation of catechol by 3,4-dihydroxybenzoate decarboxylase
      of Enterobacter cloacae P.
AB  - 3,4-Dihydroxybenzoate decarboxylase in Enterobacter cloacae P241 was induced by
      adding 3,4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, 3,4,5-trihydroxybenzoic
      acid or 4-acetamidobenzoic acid to the culture medium. After stabilizing the
      enzyme activity by adding 5 mM dithiothreitol and 20 mM Na(2)S(2)O(3) to a cell
      free extract, catechol at 50 mM was carboxylated in the presence of 3 M KHCO(3)
      to 3,4-dihydroxybenzoic acid with a molar conversion ratio of 28% after 14 h at
      30 degrees C.

PMID- 20131081
TI  - Genetic changes that increase 5-hydroxymethyl furfural resistance in ethanol
      producing Escherichia coli LY180.
AB  - The ability of a biocatalyst to tolerate furan inhibitors present in
      hemicellulose hydrolysates is important for the production of renewable
      chemicals. This study shows EMFR9, a furfural-tolerant mutant of ethanologenic E.
      coli LY180, has also acquired tolerance to 5-hydroxymethyl furfural (5-HMF). The
      mechanism of action of 5-HMF and furfural appear similar. Furan tolerance results
      primarily from lower expression of yqhD and dkgA, two furan reductases with a low
      K(m) for NADPH. Furan tolerance was also increased by adding plasmids encoding a
      NADPH/NADH transhydrogenase (pntAB). Together, these results support the
      hypothesis that the NADPH-dependent reduction of furans by YqhD and DkgA inhibits
      growth by competing with biosynthesis for this limiting cofactor.

PMID- 20131082
TI  - In vitro release behavior and cytotoxicity of doxorubicin-loaded gold
      nanoparticles in cancerous cells.
AB  - Doxorubicin (DOX), a common cancer chemotherapeutics, was conjugated to folate
      modified thiolated-polyethylene glycol-functionalized gold nanoparticles. The in
      vitro, controlled release behavior of DOX-loaded gold nanoparticles was observed
      using porous dialysis membranes (cut-off = 2 kDa). DOX-loaded gold nanoparticles
      had higher cytotoxicity for folate-receptor-positive cells (KB cells) compared to
      folate-receptor-negative cells (A549 cells) which were 48 and 62% viable for 10
      microM doxorubicin, respectively. This indicates the potential of these nano
      carriers for targeted-delivery. In addition, healthy cell viability was 69% for
      10 microM free doxorubicin whereas for the same content of drug in DOX-loaded
      nanoparticles healthy cell viability increased to 80%.

PMID- 20131083
TI  - Mesenchymal stem cells derived from human umbilical cord ameliorate
      ischemia/reperfusion-induced acute renal failure in rats.
AB  - Mesenchymal stem cells (MSCs) are candidates for cell therapy of kidney diseases.
      However, the application of MSC derived from human umbilical cord (UC-MSC) in
      treating acute renal failure (ARF) has not been reported. UC-MSCs, 10(6), were
      transplantated via the left carotid artery into ARF rats which was established by
      clamping bilateral pedicles for 60 min and reperfusing. Serum creatinine and urea
      nitrogen decreased 4.8 times and 3.6 times as well as caspase-3 and IL-1beta
      decreased 5.8 times and 9 times compared to control groups, respectively. The
      percent of proliferative cell nuclear antigen (PCNA)-positive cells (53% +/-
      7.5%) was higher than that in the control groups (17% +/- 4.5%). In addition, the
      transplanted UC-MSCs could reside in local injury sites, leading to the relief of
      hyperemia and inflammation, but no obvious transdifferentiation into renal-like
      cells. The results lay the foundation for further study on the potential
      application of UC-MSC in human disease.

PMID- 20131084
TI  - Microbial transformation of pentachloronitrobenzene under nitrate reducing
      conditions.
AB  - The effect of pentachloronitrobenzene (PCNB) on denitrification was assessed with
      two denitrifying cultures (PCNB-free control and PCNB-acclimated) developed from
      a contaminated estuarine sediment. PCNB was transformed to pentachloroaniline
      (PCA) in the PCNB-acclimated culture repeatedly amended with 0.1 muM PCNB, but
      further dechlorination or degradation of PCA was not observed for almost 1 year.
      The effect of PCNB on denitrification was also investigated with the PCNB-free
      control culture. PCNB at an initial concentration of 13 muM was transformed to
      PCA simultaneously with nitrate reduction but only after the nitrate
      concentration was at or below 20 mg N/l. PCNB addition at an initial
      concentration of 13 muM to the control denitrifying culture developed as PCNB
      free culture resulted in a transient accumulation of nitric oxide (NO) and
      nitrous oxide (N(2)O). Similarly to the PCNB-acclimated culture, PCNB
      transformation to PCA started when the nitrate concentration decreased to about
      20 mg N/l. A low degree of nitro group removal resulting in the formation of
      pentachlorobenzene (PeCB) was also observed in the control culture when amended
      with 13 muM PCNB. Further transformation or degradation of PCA was not observed
      in all cultures maintained under active nitrate reducing conditions. Based on the
      results of this study, the presence of nitrate at low concentrations in
      anoxic/anaerobic soil and sediments is not expected to negatively affect the
      biotransformation of PCNB to PCA, but dechlorination or degradation of PCA is not
      expected under active nitrate reducing conditions.

PMID- 20131085
TI  - Biodelignification of rice straw by Phanerochaete chrysosporium in the presence
      of dirhamnolipid.
AB  - Lignin degradation by white-rot fungi has received considerable attention as a
      means for reducing accumulation of lignocellulosic wastes in the environment. The
      stimulatory effect of surfactants on fungal lignocellulose bioconversion also has
      attracted wide interest. In this study the influence of dirhamnolipid
      biosurfactant on biodegradation of rice straw by Phanerochaete chrysosporium was
      investigated. It was shown that the biodelignification process of rice straw can
      be significantly enhanced by the presence of dirhamnolipid biosurfactant. In
      particular, the dirhamnolipid at the concentration of 0.007% increased the peak
      activity of lignin peroxidase (LiP) by 86% without affecting the manganese
      peroxidase (MnP) activity. The water-soluble organic carbon (WSOC) contents in
      the straw substrates as well as the microbial growth and activity were
      effectively improved by dirhamnolipid, while the degradation rate of lignin
      increased by 54% with dirhamnolipid of 0.007%. Observed chemical structural and
      morphological changes showed that the straw substrates were delignified in the
      presence of dirhamnolipid with the formation of terrace-like fragments separated
      from the inner cellular fibers and the release of simple compounds. Variation
      partitioning analysis revealed that the dirhamnolipid addition induced a
      significant straw biodelignification which explained 22.1% (P = 0.013) of the
      variance.

PMID- 20131086
TI  - The role of histone modifications and variants in regulating gene expression in
      breast cancer.
AB  - The role of epigenetic phenomena in cancer biology is increasingly being
      recognized. Here we focus on the mechanisms and enzymes involved in regulating
      histone methylation and acetylation, and the modulation of histone variant
      expression and deposition. Implications of these epigenetic marks for tumor
      development, progression and invasiveness are discussed with a particular
      emphasis on breast cancer progression.

PMID- 20131087
TI  - Epigenetic regulation of milk production in dairy cows.
AB  - It is well established that milk production of the dairy cow is a function of
      mammary epithelial cell (MEC) number and activity and that these factors can be
      influenced by diverse environmental influences and management practises
      (nutrition, milk frequency, photoperiod, udder health, hormonal and local
      effectors). Thus, understanding how the mammary gland is able to respond to these
      environmental cues provides a huge potential to enhance milk production of the
      dairy cow. In recent years our understanding of molecular events within the MEC
      underlying bovine lactation has been advanced through mammary microarray studies
      and will be further advanced through the recent availability of the bovine genome
      sequence. In addition, the potential of epigenetic regulation (non-sequence
      inheritable chemical changes in chromatin, such as DNA methylation and histone
      modifications, which affect gene expression) to manipulate mammary function is
      emerging. We propose that a substantial proportion of unexplained phenotypic
      variation in the dairy cow is due to epigenetic regulation. Heritability of
      epigenetic marks also highlights the potential to modify lactation performance of
      offspring. Understanding the response of the MEC (cell signaling pathways and
      epigenetic mechanisms) to external stimuli will be an important prerequisite to
      devising new technologies for maximising their activity and, hence, milk
      production in the dairy cow.

PMID- 20131088
TI  - Long-term evaluation of genetic counseling following false-positive newborn
      screen for cystic fibrosis.
AB  - This cross-sectional mixed method study was a long-term follow-up evaluation of
      families who participated in an earlier survey of their understanding of cystic
      fibrosis (CF) genetics and their infants' false-positive CF newborn screening
      (NBS) results. Thirty-seven of the original 138 parents participated in the
      follow-up telephone survey. Results showed parents who received genetic
      counseling at the time of their infants' diagnostic sweat tests had significantly
      higher long-term retention of genetic knowledge than those without genetic
      counseling. However, both groups still had misconceptions and lacked accurate
      information about the actual risk associated with being a CF carrier. Most
      parents either had already informed (65%) or planned to inform (19%) their
      children about the child's carrier status. Mean child age at the time of
      disclosure was 9.2 years. Situational prompts were the most common reasons for
      informing their children. Neither parental knowledge, medical literacy, nor
      parental education predicted whether parents informed their children about their
      carrier status. False-positive NBS results for CF were not associated with
      parental perceptions of child vulnerability 11-14 years after the testing.
      Although the sample from this study was small, these findings underscore the
      benefits of genetic counseling at the time of the diagnostic sweat test and offer
      information that can assist parents in talking with their children about the
      implications of having one CFTR mutation.

PMID- 20131089
TI  - Stable patterns of AH block arising from longitudinal dissociation and reentry
      within the superfused rabbit AV junction.
AB  - INTRODUCTION: Multiple forms of antegrade AH Wenckebach block (WB) observed in 14
      of 221 superfused rabbit AV junctions. METHODS: Bipolar and microelectrode
      recordings were used to examine the mechanism of multiple forms of AH WB.
      RESULTS: Each of the 14 preparations demonstrated typical 3:2 and 2:1 AV block,
      but also demonstrated longitudinal dissociation within the slow pathway input (N
      = 11) or compact AV node (N = 3). A 3:2 WB in one pathway and 1:1 conduction in a
      parallel pathway summated to provide antegrade conduction of the third atrial
      beat. Retrograde conduction (reentry) blocked conduction of the fourth impulse
      (4:3 block). A 5:4 block was similarly observed, with summation providing for
      antegrade AH activation of the third and fourth atrial beats. Retrograde
      activation observed with the fourth beat, terminated antegrade conduction of the
      fifth beat. CONCLUSIONS: The studies demonstrate multiple AH WB patterns
      consistent with rate-dependent longitudinal dissociation, summation of
      dissociated AV conduction pathways, and retrograde conduction block within the AV
      junction.

PMID- 20131090
TI  - Suppression of pain-related thoughts and feelings during pain-induction: sex
      differences in delayed pain responses.
AB  - Women tend to report greater acute and chronic pain intensity than men, and
      various mechanisms have been proposed to account for these sex differences.
      Suppression has been related to amplified pain intensity, and thus we examined
      whether sex differences in the use of suppression partly explained the
      discrepancy between men and women on pain report. Participants (N = 222; women:
      55%) underwent a cold pressor, during which half the sample was randomly assigned
      to suppress pain-related thoughts and feelings and the other half was not. A 2
      min recovery period followed the cold pressor. Ten min later, all participants
      were exposed to another physical stimulus (a massage device). Significant
      condition x Sex interactions were found for pain intensity, sensory ratings from
      the McGill Pain Questionnaire and unpleasantness ratings for the massage device,
      such that: (a) men in the No Suppression condition reported lower pain and
      unpleasantness than women in the same condition; (b) men in Suppression condition
      reported greater pain and unpleasantness then men in No Suppression condition,
      but equivalent pain and unpleasantness to women in No Suppression condition; (c)
      differences between men and women on pain in No Suppression condition were partly
      mediated by women's report of greater spontaneous use of avoidance/suppression
      during the cold pressor. Results using an "addition" paradigm (i.e., manipulating
      use of suppression) and a "take away" (i.e., mediation) paradigm converge to
      suggest that women spontaneously use suppression to regulate pain more than men,
      and that the differential use of suppression partly explains the tendency for
      women to report greater pain intensity than men.

PMID- 20131091
TI  - Impact assessment of subsurface drainage on waterlogged and saline lands.
AB  - Waterlogging and salinity due to seepage from canals have polluted land and
      environment in various parts of Pakistan. A sustainable environment requires
      urgent remedial measures for this problem. The research in this paper presents
      the impacts of the Fourth Drainage Project, Faisalabad on the twin problem of
      waterlogging and salinity. Monitoring of the project was made on regular basis.
      The key performance indicators for the project include the lowering of water
      table, improvement of water quality and soil salinity, increase in area under
      cultivation, cropping intensity, and socioeconomic status of the project
      population. Data regarding water levels and discharge from the drain pipes were
      collected to monitor the impact on waterlogging. Soil samples were tested to
      evaluate the impact of drainage on land. It has been found that the percentage of
      the contaminated land in the project area has considerably been decreased, while
      the cropping intensities have been increased.

PMID- 20131092
TI  - Integrated real-time monitoring system to investigate the hypoxia in a shallow
      wind-driven bay.
AB  - Corpus Christi Bay (Texas, USA) is a shallow wind-driven bay which experiences
      hypoxia (dissolved oxygen < 2 mg/L) during the summer. Since this bay is a very
      dynamic system, the processes that control the hypoxia can last on the order of
      hours to days. Monitoring systems installed on a single type of platform cannot
      fully capture these processes at the spatial and temporal scales of interest.
      Therefore, we have integrated monitoring systems installed on three different
      platform types: (1) fixed robotic, (2) mobile, and (3) remote. On the fixed
      robotic platform, an automated profiler system vertically moves a suite of water
      quality measuring sensors within the water column for continuous measurements. An
      integrated data acquisition, communication and control system has been configured
      on our mobile platform (research vessel) for synchronized measurements of
      hydrodynamic and water quality parameters at greater spatial resolution. In
      addition, a high-frequency radar system has been installed on remote platforms to
      generate surface current maps for the bay. With our integrated system, we were
      able to capture evidence of a hypoxic event in summer 2007; moreover, we detected
      low dissolved oxygen conditions in a part of the bay with no previously reported
      history of hypoxia.

PMID- 20131093
TI  - A milk-based wolfberry preparation prevents prenatal stress-induced cognitive
      impairment of offspring rats, and inhibits oxidative damage and mitochondrial
      dysfunction in vitro.
AB  - Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae.
      The red-colored fruits of L. barbarum have been used for a long time as an
      ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal
      medicine for improving health. However, its effects on cognitive function have
      not been well studied. In the present study, prevention of a milk-based wolfberry
      preparation (WP) on cognitive dysfunction was tested in a prenatal stress model
      with rats and the antioxidant mechanism was tested by in vitro experiments. We
      found that prenatal stress caused a significant decrease in cognitive function
      (Morris water maze test) in female offspring. Pretreatment of the mother rats
      with WP significantly prevented the prenatal stress-induced cognitive
      dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl
      and superoxide radicals (determined by an electron spin resonance spectrometric
      assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue
      and tissue mitochondria, including increases in reactive oxygen species and lipid
      peroxidation and decreases in the activities of complex I, complex II, and
      glutamate cysteine ligase. These results suggest that dietary supplementation
      with WP may be an effective strategy for preventing the brain oxidative
      mitochondrial damage and cognitive dysfunction associated with prenatal stress.

PMID- 20131095
TI  - Determinants of barriers to treatment for anxiety disorders.
AB  - The objectives of this study were to evaluate perceived unmet need for mental
      healthcare, determinants of unmet need, and barriers to care in individuals with
      social anxiety (SA) or panic disorder with agoraphobia (PDA) in Quebec. Data from
      206 participants diagnosed with SA or PDA were collected using an online
      questionnaire. Correlational analyses and binary stepwise logistic regressions
      were conducted to explore determinants of perceived unmet need. Of the 206
      participants, 144 (69.9%) reported instances of unmet need for treatment.
      Perceived unmet need was correlated with variables related to the severity of the
      disorder, such as comorbid depression, avoidance, duration of worry, interference
      with functioning, and time lapsed between the appearance of first symptoms and
      first consultation. Depression and avoidance emerged as predictors for perceived
      unmet need in the regression analysis. The most common barriers to treatment
      reported were concern about the cost of services (63.9%), not knowing where to go
      to get help (63.2%), lack of health insurance coverage (52.4%), and appointment
      wait times (52.1%). The results of this study demonstrate the need to overcome
      barriers to treatment engendered by avoidance behaviors associated with anxiety.
      Potential methods for achieving this objective include Internet outreach, support
      groups, and increased accessibility to public services.

PMID- 20131096
TI  - Simulated stand tests and centrifuge training to prevent orthostatic intolerance
      on Earth, moon, and Mars.
AB  - One proposed method to overcome postflight orthostatic intolerance is for
      astronauts to undergo inflight centrifugation. Cardiovascular responses were
      compared between centrifuge and gravitational conditions using a seven
      compartment cardiovascular model. Vascular resistance, heart rate, and stroke
      volume values were adopted from literature, while compartmental volumes and
      compliances were derived from impedance plethysmography of subjects (n=8) riding
      on a centrifuge. Three different models were developed to represent the typical
      male subject who completed a 10-min postflight stand test ("male finisher"), "non
      finishing male" and "female" (all non-finishers). A sensitivity analysis found
      that both cardiac output and arterial pressure were most sensitive to total blood
      volume. Simulated stand tests showed that female astronauts were more susceptible
      to orthostatic intolerance due to lower initial blood pressure and higher
      pressure threshold for presyncope. Rates of blood volume loss by capillary
      filtration were found to be equivalent in female and male non-finishers, but four
      times smaller in male finishers. For equivalent times to presyncope during
      centrifugation as those during constant gravity, lower G forces at the level of
      the heart were required. Centrifuge G levels to match other cardiovascular
      parameters varied depending on the parameter, centrifuge arm length, and the
      gravity level being matched.

PMID- 20131097
TI  - Application of recombinant fusion proteins for tissue engineering.
AB  - Extracellular matrix (ECM) plays important roles in tissue engineering because
      cellular growth and differentiation, in the two-dimensional cell culture as well
      as in the three-dimensional space of the developing organism, require ECM with
      which the cells can interact. Also, the development of new synthetic ECMs is very
      important because ECMs facilitate the localization and delivery of cells to the
      specific sites in the body. Therefore, the development of synthetic ECMs to
      replace the natural ECMs is increasingly essential and promising in tissue
      engineering. Recombinant genetic engineering method has enabled the synthesis of
      protein-based polymers with precisely controlled functionalities for the
      development of new synthetic ECMs. In this review, the design and construction of
      structure-based recombinant fusion proteins such as elastin-like polymers (ELPs)
      and silk-like polymers (SLPs), cell-bound growth factor-based recombinant fusion
      proteins such as basic fibroblast growth factor (bFGF) and epidermal growth
      factor (EGF), hybrid system composed of recombinant protein and synthetic
      polymer, and E-cadherin-based fusion protein by recombinant genetic engineering
      were explained for application of the synthetic ECMs. Modulation of mechanical
      properties, stimuli-sensitivity, biodegradation and cell recognition can be
      achieved through precise control of sequence, length, hydrophobicity and cell
      binding domain by recombinant genetic engineering.

PMID- 20131098
TI  - Towards non-thrombogenic performance of blood recirculating devices.
AB  - Implantable blood recirculating devices have provided life saving solutions to
      patients with severe cardiovascular diseases. However, common problems of
      hemolysis and thromboembolism remain an impediment to these devices. In this
      article, we present a brief review of the work by several groups in the field
      that has led to the development of new methodologies that may facilitate
      achieving the daunting goal of optimizing the thrombogenic performance of blood
      recirculating devices. The aim is to describe work which pertains to the
      interaction between flow-induced stresses and the blood constituents, and that
      supports the hypothesis that thromboembolism in prosthetic blood recirculating
      devices is initiated and maintained primarily by the non-physiological flow
      patterns and stresses that activate and enhance the aggregation of blood
      platelets, increasing the risk of thromboembolism and cardioembolic stroke. Such
      work includes state-of-the-art numerical and experimental tools used to elucidate
      flow-induced mechanisms leading to thromboembolism in prosthetic devices.
      Following the review, the paper describes several efforts conducted by some of
      the groups active in the field, and points to several directions that should be
      pursued in the future in order to achieve the goal for blood recirculating
      prosthetic devices becoming more effective as destination therapy in the future.

PMID- 20131099
TI  - Sporotrichosis caused by Sporothrix globosa in Rio De Janeiro, brazil: case
      report.
AB  - This report describes the first isolation of Sporothrix globosa from a Brazilian
      patient. A 77-year-old woman was examined for sporotrichosis infection.
      Histopathological examination of skin biopsy revealed chronic granulomatous
      infiltrate with microabcess. Furthermore, S. schenckii-like yeasts were evident
      as demonstrated by PAS and Grocott stains. The fungus was identified based on
      colony morphology on Sabouraud Dextrose Agar slants, Potato Dextrose Agar, and
      Corn Meal Agar, microscopic morphology on slides cultures, and assimilation of
      different carbon sources. The species confirmation was made by molecular
      methodology.

PMID- 20131100
TI  - Adverse anthropometric risk profile in biochemically controlled acromegalic
      patients: comparison with an age- and gender-matched primary care population.
AB  - GH and IGF-1 play an important role in the regulation of metabolism and body
      composition. In patients with uncontrolled acromegaly, cardiovascular morbidity
      and mortality are increased but are supposed to be normalised after biochemical
      control is achieved. We aimed at comparing body composition and the
      cardiovascular risk profile in patients with controlled acromegaly and controls.
      A cross-sectional study. We evaluated anthropometric parameters (height, weight,
      body mass index (BMI), waist and hip circumference, waist to height ratio) and,
      additionally, cardiovascular risk biomarkers (fasting plasma glucose, HbA1c,
      triglycerides, total cholesterol, HDL, LDL, and lipoprotein (a), in 81
      acromegalic patients (58% cured) compared to 320 age- and gender-matched controls
      (ratio 1:4), sampled from the primary care patient cohort DETECT. The whole group
      of 81 acromegalic patients presented with significantly higher anthropometric
      parameters, such as weight, BMI, waist and hip circumference, but with more
      favourable cardiovascular risk biomarkers, such as fasting plasma glucose, total
      cholesterol, triglycerides and HDL levels, in comparison to their respective
      controls. Biochemically controlled acromegalic patients again showed
      significantly higher measurements of obesity, mainly visceral adiposity, than age
      and gender-matched control patients (BMI 29.5 +/- 5.9 vs. 27.3 +/- 5.8 kg/m(2);
      P = 0.020; waist circumference 100.9 +/- 16.8 vs. 94.8 +/- 15.5 cm; P = 0.031;
      hip circumference 110.7 +/- 9.9 vs. 105.0 +/- 11.7 cm; P = 0.001). No differences
      in the classical cardiovascular biomarkers were detected except for fasting
      plasma glucose and triglycerides. This effect could not be attributed to a higher
      prevalence of type 2 diabetes mellitus in the acromegalic patient group, since
      stratified analyses between the subgroup of patients with acromegaly and
      controls, both with type 2 diabetes mellitus, revealed that there were no
      significant differences in the anthropometric measurements. Biochemically cured
      acromegalic patients pertain an adverse anthropometric risk profile, mainly
      because of elevated adiposity measurements, such as BMI, waist and hip
      circumference, compared to an age- and gender-matched primary care population.

PMID- 20131101
TI  - Non-cirrhotic extrahepatic portal vein thrombosis: a 6-year long case history.

PMID- 20131102
TI  - Primary mediastinal (thymic) large B cell lymphoma with aberrant expression of
      CD3: a case report with review of the literature.
AB  - We report the first case of primary mediastinal large B cell lymphoma (PMBL) with
      aberrant expression of CD3. PMBL is a subtype of diffuse large B cell lymphoma
      (DLBCL) and usually presents with bulky mediastinal lesions. Lineage
      ambiguity/infidelity is uncommon in DLBCL but has been described in sporadic case
      reports/series. A literature search identifies 13 additional cases of DLBCL
      expressing CD3, with the majority displaying cytoplasmic expression. Of the 14
      total cases, 6 are pyothorax-associated lymphoma, 4 are conventional DLBCL, 2 are
      plasmablastic lymphoma, one is primary effusion lymphoma and one is PMBL. Two
      cases show genotypic ambiguity/infidelity with dual clonal IG and TCR gene
      rearrangements in addition to ambiguous immunophenotypes. Of the 13 cases tested
      for EBV status, 11 are positive, suggesting an important role of EBV in promoting
      lineage ambiguity/infidelity. A low threshold for testing EBV status is advocated
      in DLBCL with phenotypic ambiguity along with panels of immunohistochemical and
      molecular studies.

PMID- 20131103
TI  - Glycosylation-modified erythropoietin with improved half-life and biological
      activity.
AB  - Erythropoietin (EPO) controls the production of red blood cells, so it is
      important to maintain high levels of EPO activity and half-life. Here, we
      modified glycosylation sites in human erythropoietin (HuEPO) gene, resulting in
      proteins with addition of 1-4 glycosylation sites. The modified gene was
      introduced into CHO cells. The expressed EPO analogs were analyzed by SDS-PAGE.
      Half-life of the analogs was determined by sialic acid content test. In vivo
      potencies of analogs were evaluated by reticulocyte count and haematocrit level.
      The metabolic clearance of recombinant human erythropoietin (rHuEPO) and its
      analogs were determined by EPO immunoradiometrics assay. We have shown that the
      carbohydrate content in modified EPO molecules is increased. The modified EPO,
      [Val(3)Asn(4)Thr(6)Asn(30)Thr(32)Val(87)Asn(88)Thr(90)]EPO, increases 3.3 times
      in elimination half-life, 2.1 times in activity and prolongs 2 days functional
      time in vivo in comparison to rHuEPO. These findings suggest that the addition of
      glycosylation sites in EPO enhances half-life and biological activity of EPO,
      duration of action of EPO anlogues positively correlated with the number of
      glycosylated sites, while addition of 4 glycosylation sites does not further
      enhance the erythropoietic potency.

PMID- 20131104
TI  - Extreme eosinophilia caused by interleukin-5-producing disseminated colon cancer.

PMID- 20131105
TI  - Of babies and bathwater: a reply to Coyne and Tennen's views on positive
      psychology and health.
AB  - PURPOSE: We disagree with several conclusions reached by Coyne and Tennen, as
      well as their interpretation of specific findings. RESULTS: First, we dispute
      that researchers have advanced the claim that positive thinking can cure disease.
      Second, we question their exclusive focus on cancer-related mortality, when
      strong cumulative evidence suggests that optimism is related to positive health
      outcomes for other major diseases, and that psychosocial interventions may
      improve other important cancer outcomes, such as reduced pain and increased
      quality of life. Third, we disagree sharply with their assessment of the
      literature on posttraumatic growth and the implications of the research they
      cite. CONCLUSION: It is premature to abandon efforts to understand and promote
      positive phenomena among people with various life-threatening illnesses. Instead,
      well-validated measures of positive phenomena should become routinely
      incorporated into a broader array of health psychology studies to provide a
      rigorous test of their role in human health and adaptation to disease.

PMID- 20131106
TI  - New practice guidelines for perioperative beta blockade from the United States
      and Europe: incremental progress or a necessary evil?

PMID- 20131107
TI  - New concepts regarding cerebral vasospasm: glial-centric mechanisms.
AB  - PURPOSE: Poor outcome in patients with cerebral vasospasm following subarachnoid
      hemorrhage remains a serious clinical problem. The current management with focus
      on the cerebrovascular constriction accounts for the use of "triple-H" therapy
      (hypertension, hypervolemia, and hemodilution) to enhance cerebral blood flow
      through constricted vessels. Recent work suggests that spreading depression (a
      stereotypical response of cerebral cortical tissue to noxious stimuli with
      subsequent oligemic blood flow) occurs in patients with cerebral vasospasm. A
      narrative review was conducted to examine the relationship between spreading
      depression and subarachnoid hemorrhage and to identify the anesthetic effects on
      the propagation of spreading depression. PRINCIPAL FINDINGS: Following review of
      the literature, an underlying mechanism is advanced that cerebral vasospasm is
      not primarily a problem of the cerebral vasculature but a consequence of glial
      cell dysfunction following spreading depression - a glial-centric cause for
      vasospasm. Such a mechanism for vasospasm becomes manifest when spreading
      depression waves transition to peri-infarct depolarization waves - with
      protracted ischemic blood flow in compromised tissue. The extracellular
      microenvironment with high potassium and low nitric oxide tension can account for
      conducting vessel narrowing. CONCLUSIONS: The implication for clinical management
      is discussed supposing glial cell dysfunction is an underlying mechanism
      responsible for the vascular spasm.

PMID- 20131108
TI  - The effect of unanticipated perioperative death on anesthesiologists.
AB  - PURPOSE: Unanticipated perioperative death (UPD) is a significant event for the
      anesthesiologist that has not been widely studied. An anonymous questionnaire was
      used to obtain information about the frequency of UPD, anesthesiologists' most
      significant UPD, and their opinions regarding UPD. METHODS: A questionnaire was
      mailed to all anesthesiologists who were registered with the College of
      Physicians and Surgeons of Alberta in 2005 (n = 285). RESULTS: The study achieved
      a 63% response rate. Sixty-four percent of respondents had been in practice for
      more than ten years, and 53% of respondents had experienced at least one UPD.
      After the UPD, 46% of the respondents performed further elective cases the same
      day, although 62% of them indicated that this was not advisable. Personal
      consequences were reported. Twenty-five percent felt they were being blamed for
      the event, and 10% thought about the UPD on a daily basis for more than a year
      afterwards. Mortality and morbidity reviews were common, and disciplinary
      consequences occurred infrequently. Sixty-four percent of anesthesiologists' most
      significant UPDs were elective cases. The etiology of death was thought to be
      anesthesia-related in only 11% of the UPDs. Although most respondents agreed that
      supportive and educational activities in the aftermath were advisable, such
      activities occurred in a minority of cases. CONCLUSIONS: Alberta
      anesthesiologists are likely to experience UPD during their careers, and the
      experience can be associated with important personal consequences. Support for
      the anesthesiologist is inconsistent, and many continued to perform elective
      cases immediately following UPD. These conditions were not supported by the
      majority of respondents.

PMID- 20131110
TI  - The essential role of GhPEL gene, encoding a pectate lyase, in cell wall
      loosening by depolymerization of the de-esterified pectin during fiber elongation
      in cotton.
AB  - Cotton fiber elongation, largely achieved by cell wall loosening, is an important
      stage during cotton fiber development. In this present research, a fiber
      preferential cDNA encoding a pectate lyase (PEL) which could exclusively degrade
      the de-esterified pectin was isolated from a cotton (Gossypium hirsutum) fiber
      cDNA library. Subsequently, the corresponding PEL genes were isolated from four
      different cotton species and characterized. In vitro enzyme assays indicated that
      GhPEL really exhibited cleavage-activity against de-esterified pectin. The
      temporal-spatial expression analyses revealed that the GhPEL gene was
      preferentially expressed in fibers at 10 days-post anthesis (DPA). Antisense
      GhPEL transgenic cotton plants were generated by Agrobacterium-mediated
      transformation. Six homozygous lines, each with one or two copies of the
      transgene inserted as determined by southern blot analysis of the NPTII gene,
      were selected for further functional analysis. The GhPEL expression during fiber
      elongation in these transgenic lines was significantly suppressed in various
      degrees. Furthermore, the reduction of GhPEL enzymatic activity by decreasing
      GhPEL transcripts severely affected the degradation of de-esterified pectin in
      primary cell walls of transgenic cotton fibers, which consequently blocked cell
      wall loosening in early fiber development. Ultimately, the fiber elongation of
      all these transgenic lines was repressed. These results suggested that GhPEL may
      play an important role in the process of normal fiber elongation in cotton.

PMID- 20131111
TI  - Prehospital emergency physician activation of interventional cardiology team
      reduces door-to-balloon time in ST-elevation myocardial infarction.
AB  - QUESTION UNDER STUDY: To explore whether early activation of an interventional
      cardiology team, by prehospital emergency physicians, reduces door-to-balloon
      time (DTBT) in patients with ST-elevation myocardial infarction (STEMI) diagnosed
      with prehospital ECG. METHODS:  DESIGN: before-after comparison. SETTING:
      emergency department (ED) of an urban teaching hospital with a catheterisation
      laboratory open continuously. STUDY SUBJECTS: patients with STEMI diagnosed in
      the prehospital setting or in the ED within 12 hours of symptoms. INTERVENTION: a
      paging system or "STEMI alarm", activated by prehospital physicians, which
      simultaneously notified both the catherisation laboratory and cardiology teams
      before the patient's arrival to the ED. OUTCOME MEASURES: DTBT and the proportion
      of patients with DTBT <90 minutes. RESULTS: A total of 196 patients were
      included; 77 before and 119 after implementation of the "STEMI alarm". Between
      the two periods, median DTBT decreased from 109 to 76 minutes (p <0.001) and the
      proportion of patients treated within 90 minutes increased from 36% to 66% (p
      <0.001). During intervention, the STEMI alarm was activated in 67 patients (56%).
      In these cases the median DTBT was 50 minutes, with 96% within 90 minutes. The
      alarm was inappropriately activated in 9 cases (11%). CONCLUSIONS:
      Catheterisation laboratory activation by a prehospital emergency physician
      markedly reduces DTBT in STEMI patients.

PMID- 20131112
TI  - Assessment of an Interferon-gamma release assay for the diagnosis of latent
      tuberculosis infection in haemodialysis patient.
AB  - BACKGROUND: The accurate diagnosis of latent tuberculosis infection (LTBI) in
      haemodialysis patients remains elusive. Impaired immune function associated with
      chronic kidney failure causes a high number of anergic tuberculin skin tests
      (TST). Interferon-gamma (INF-gamma) release assays (IGRAs) measuring the INF
      gamma secretion of tuberculosis specific T-cells have several advantages over the
      TST but their significance in dialysis patients is currently uncertain. METHODS:
      This study examines the test-performances of the QuantiFERON Gold InTube (QFT
      GIT) in a cohort of 39 haemodialysis (HD) patients and 52 healthy individuals.
      RESULTS: INF-gamma secretion in HD patients was significantly lower than in
      healthy controls, however, mitogen-anergic QFT-GIT results were only found in
      2.5% of HD-patients. INF-gamma secretion was independent of duration of HD
      treatment, dialysis quality and nutritional status. The QFT-GIT showed a closer
      association with TB risk factors as a proxy for past exposure to TB than the TST.
      CONCLUSIONS: We conclude that the QFT-GIT is a valid alternative to the TST.
      Together with the survey of TB risk factors, it may help to diagnose LTBI more
      accurately in HD-patients.

PMID- 20131113
TI  - The acanthocyte-echinocyte differential: The example of chorea-acanthocytosis.
AB  - Acanthocytes are a distinct structural (and functional) entity compared to
      echinocytes. The differential, however, is not always clear. A summary of
      morphologic characteristic to make a clear distinction is provided, using the
      blood of a rare neurologic disease with acanthocytic transformation of red blood
      cells.

PMID- 20131114
TI  - "I'll look it up on the Web first": Barriers and overcoming barriers to consult
      for sexual dysfunction among young men.
AB  - QUESTIONS UNDER STUDY: Our aim was to identify the barriers young men face to
      consult a health professional when they encounter sexual dysfunctions and where
      they turn to, if so, for answers. METHODS: We conducted an exploratory
      qualitative research including 12 young men aged 16-20 years old seen in two
      focus groups. Discussions were triggered through vignettes about sexual
      dysfunction. RESULTS: Young men preferred not to talk about sexual dysfunction
      problems with anyone and to solve them alone as it is considered an intimate and
      embarrassing subject which can negatively impact their masculinity.
      Confidentiality appeared to be the most important criterion in disclosing an
      intimate subject to a health professional. Participants raised the problem of
      males' accessibility to services and lack of reason to consult. Two criteria to
      address the problem were if it was long-lasting or considered as physical. The
      Internet was unanimously considered as an initial solution to solve a problem,
      which could guide them to a face-to-face consultation if necessary. CONCLUSIONS:
      Results suggest that Internet-based tools should be developed to become an easy
      access door to sexual health services for young men. Wherever they consult and
      for whatever problem, sexual health must be on the agenda.

PMID- 20131115
TI  - Delirium upon admission to Swiss nursing homes: a cross-sectional study.
AB  - QUESTIONS UNDER STUDY: We wished to investigate the prevalence of delirium in
      patients upon admission to nursing homes and whether or not the previous place of
      residence predicts delirium. METHODS: The Resident Assessment Instrument Minimum
      Data Set (RAI-MDS) and the Nursing Home Confusion Assessment Method (NHCAM) were
      used to determine whether the previous place of residence (community, nursing
      home, acute care, psychiatric, rehabilitation hospital) predicted the prevalence
      of sub-syndromal or full delirium in nursing home residents in three Swiss
      cantons (n = 11745). RESULTS: 39.7% had sub-syndromal and 6.5% had full delirium.
      Lower cognitive performance and increased depressive symptoms were significant
      predictors of higher NHCAM values independent of previous residence. Age, civil
      status, continence, newly introduced drugs, and basic activities of daily living
      were predictors in some resident groups. The variance of NHCAM scores explained
      varied between 25.1% and 32.3% depending on previous residence. CONCLUSIONS: Sub
      syndromal and full delirium are common upon nursing home admission. Increased
      dependence and depression are consistently associated with higher NHCAM scores.
      Patients from psychiatric settings have an increased risk of delirium. Although
      factors associated with delirium depend on a patient's previous residence, all
      patients must be carefully screened for sub-syndromal and full delirium.

PMID- 20131116
TI  - Acute effect of nitroglycerin on cyclosporine-induced hypertension after cardiac
      transplantation.
AB  - BACKGROUND: Cyclosporine represents a milestone in immunosuppression following
      organ transplantation. Its use, however, comes at the cost of significant side
      effects, such as arterial hypertension which is rarely controllable by currently
      available anti-hypertensive drugs. The aim was to investigate the effect of acute
      administration of nitroglycerin in heart-transplanted patients with cyclosporine
      induced hypertension. METHODS: The sample included 18 cyclosporine-induced
      hypertensive patients (HTX group) scheduled for elective cardiac catheterization
      following heart transplantation, as well as 6-matched essential hypertensive
      patients (HT group). The blood pressure (BP) in the aorta and pulmonary artery,
      before and after administration of nitroglycerin, was measured simultaneously.
      RESULTS: After injection of 50 ug and 100 ug nitroglycerin, BP significantly
      decreased both in HTX (systolic (s) BP p = 0.0001; diastolic (d) BP p = 0.0001)
      and in controls (sBP p = 0.006; dBP p = 0.05). This reduction was more pronounced
      in HTX (sBP p = 0.022; dBP p = 0.018 for group-comparison). Following analysis of
      the data in relation to its individual baseline, a significantly higher reduction
      of the BP induced by 100 ug nitroglycerin was observed in the HTX group compared
      to the HT group (p = 0.02 for sBP and p = 0.03 for dBP). 8 +/- 3 minutes after
      the last nitrate infusion, BP remained significantly reduced compared to baseline
      in HTX (p <0.001), whereas it came back to baseline in controls. The reduction in
      sBP was correlated to cyclosporine A levels (p = 0.04 after 50ug nitroglycerin; p
      = 0.05 after 100 ug nitroglycerin). CONCLUSION: After application of
      nitroglycerin, sBP is reduced immediately in HTX with uncontrolled cyclosporine
      induced hypertension. Further studies are needed to evaluate the long-term effect
      of nitrates in these patients.

PMID- 20131117
TI  - Integration of complementary and alternative medicine at medical schools?

PMID- 20131118
TI  - Complementary medicine courses in Swiss medical schools: actual status and
      students' experience.
AB  - BACKGROUND: In line with growing public popularity of complementary and
      alternative medicine (CAM), courses in CAM have been implemented in Medical
      Schools internationally, but as yet in an uncoordinated and heterogeneous way. In
      Switzerland, comprehensive data about CAM education at Medical Faculties are
      lacking. OBJECTIVES: To survey courses at Swiss Medical Schools, document medical
      students' attitude toward and knowledge of CAM and their experience of CAM
      courses at medical schools. The aim was to determine the relationship between the
      presence/absence of CAM courses at each medical school and students' attitude
      toward, knowledge of, and motivation to learn about CAM. METHODS: Data about
      current courses in CAM were collected from the websites of the five Swiss Medical
      Schools and from an online questionnaire addressed to the CAM teachers (n = 13).
      All Swiss senior medical students (n = 640) were surveyed by an anonymous online
      questionnaire. RESULTS: There are two chairs for CAM in Bern and Zurich, CAM
      familiarisation courses are provided by external teachers in Basel and Lausanne,
      and there was no CAM education in Geneva. 38.3% of the senior medical students
      replied to the survey. 80.0% of the students who visited CAM courses stated that
      they have improved their knowledge of CAM. There was no relationship between the
      presence of CAM education and a significant elevation of the self-assessed
      knowledge of CAM of the students. CAM education has no significant influence on
      students' opinions about CAM, nor does it significantly motivate them to deepen
      their study of CAM. Form, frequency and content of CAM courses are similarly as
      heterogeneous as in other countries. CONCLUSIONS: There is no coordination or
      standard for CAM courses in Swiss Medical Schools. Our results suggest an overall
      positive attitude toward and positive personal experiences with CAM of Swiss
      medical students', but a relationship between the absence or presence of CAM
      courses and students attitudes and knowledge could not be found. A coordinated
      policy towards the integration of CAM in medical curricula is strongly
      recommended.

PMID- 20131119
TI  - Patient satisfaction and clinical outcome following outpatient radiofrequency
      catheter ablation of supraventricular tachycardia.
AB  - BACKGROUND: Catheter ablation is an effective and safe treatment for various
      arrhythmic disorders. Patients are frequently admitted for an overnight stay
      after the ablation procedure to monitor for possible postprocedural complications
      or recurrence of the arrhythmia. The aim of this study was to assess patient
      satisfaction in patients with supraventricular tachycardia following catheter
      ablation on an outpatient basis. METHODS: 243 consecutive patients (129 male,
      53%; mean age 49 +/- 17 years) underwent electrophysiological study and
      radiofrequency catheter ablation either on an outpatient basis or a
      hospitalisation that included at least an overnight hospital stay (inpatient) at
      a university hospital. All patients were asked to complete a specially designed
      questionnaire that addressed patient satisfaction as well as the clinical outcome
      after ablation at six months. RESULTS: The ablation procedure was performed on an
      outpatient basis in 119 patients (49%). The long-term procedural success rate was
      99%. The overall patient satisfaction with the ablation procedure and with the
      clinical outcome at six months was 90%. There were no significant differences
      between outpatient and inpatient groups with respect to ablation results and
      patient satisfaction. Patients in the outpatient group returned to work after 2.8
      +/- 1.9 days as compared to 3.9 +/- 2.2 days in the in hospital group (p =
      0.001). CONCLUSION: Overall patient satisfaction and self-reported clinical
      outcome are comparable for outpatient and inpatient catheter ablations. Patients
      undergoing outpatient procedures may return to work earlier. Therefore,
      outpatient ablation procedures may be considered for selected patients without
      significant comorbidities.

PMID- 20131120
TI  - Evolution of overweight and obesity among elementary school children in Geneva.
AB  - QUESTIONS UNDER STUDY: In view of the alarming trend in childhood obesity (O) and
      overweight (OW) observed in certain countries, the aim of the study is to measure
      the prevalence of O and OW in successive cohorts of elementary school children in
      Geneva. METHODS: All 5-6-year-old children attending public schools in the Canton
      of Geneva were measured and weighed during a systematic health check at school
      from 2003 to 2008. BMI was calculated and plotted on standardised BMI for age
      tables, using Cole's and Kromeyer's references. RESULTS: Using Cole's references,
      the overall trend was a small non-significant decrease for OW 0.7 points (p =
      0.33) and O 0.5 points (p = 0.23) over the 5-year period. For girls, OW decreased
      by 1.1 point (p = 0.47) and O decreased by 0.5 points (p = 0.61), whilst for boys
      OW decreased by 0.3 points (p = 0.54) and O decreased by 0.6 points (p = 0.23). A
      non-significant decrease or stabilisation in the prevalence of overweight and
      obesity was observed over the 5-year period in both boys and girls. CONCLUSION:
      These observations corroborate observations from Sweden and France, showing a
      levelling off in obesity and overweight in young children.

PMID- 20131121
TI  - Barriers to Swiss guideline-recommended cholesterol management in general
      practice.
AB  - BACKGROUND: Standard guidelines for the management of dyslipidaemia are often not
      followed in general practice. The reasons for guideline non-adherence are not
      known. METHODS: Charts of 1000 consecutive unselected patients of 20 general
      practitioners in northwestern Switzerland were reviewed. An independent committee
      of experienced study physicians checked the data and assessed the reasons for not
      measuring plasma cholesterol and for not treating dyslipidaemia as recommended by
      guidelines. RESULTS: Complete data of 866 patients were studied. 29% of all
      patients qualified for secondary prevention. 6% had no additional cardiovascular
      risk factors (apart from cholesterol values), 24% had one and 41% had 2 or more
      additional cardio- vascular risk factors. Guidelines were followed in 44% of all
      cases and were not followed in 56%. In 37.5% of all cases we found diagnostic
      guideline non-adherence, and in 10% only treatment guideline non-adherence. 8.5%
      of all patients had both diagnostic and treatment non-adherence. The main reasons
      for diagnostic non-adherence were relevant comorbidity (45%) and GPs' belief that
      the risk did not require screening (42%). The main reasons for treatment non
      adherence were GPs' belief that the risk did not require treatment (42%) and
      relevant comorbidity (38%). CONCLUSION: More than half of all patients aged 35-80
      years are not screened or treated according to current guidelines. The reasons
      are to an equal extent patient-related (relevant comorbidity) and physician
      related (acceptance and knowledge of guidelines). These reasons should be
      considered when programmes to improve the quality of GPs' adherence to guidelines
      are implemented.

PMID- 20131122
TI  - Smoking cessation counselling: impact of chart stickers and resident training.
AB  - OBJECTIVES: To assess the effect of a training program for smoking cessation
      combined with chart stickers on resident's (physicians-in-training) practice of
      counselling smoking patients. SETTING: A single centre prospective observational
      study at the Basel University Hospital Medical Outpatient Department. METHODS:
      456 consecutive outpatients were contacted by phone within 24 hours of their
      initial consultation. Information concerning questions asked about smoking and/or
      cessation advice provided by the resident to patients was collected and compared
      with a historical pre-interventional cohort using the identical questionnaire and
      study design. RESULTS: Of 272 patients included, 106 (39%) were current smokers,
      123 (45%) had never smoked, and 43 (16%) were former smokers. The mean age was 43
      +/- 11 (range 16-87) years and 49% were male. Equal proportions of participants
      were in the pre-contemplation (40%) and contemplation stages (42%), 16% were
      preparing to quit and 2% had stopped in the previous 6 months. Results related to
      smoking cessation advice were compared to those obtained during an identical
      survey one year earlier performed prior to the intervention (pre-interventional).
      Residents questioned 82% (pre-interventional 81%) of the patients about smoking
      and inquired about smoking duration in 71% (pre-interventional 44%) of the
      patients. 46% (pre-interventional 28%) of the patients received information on
      smoking-related risks, whereas cessation was discussed with 32% (pre
      interventional 10%) and offered to 23% (pre-interventional 9%) of the patients.
      CONCLUSION: Compared with a historical pre-interventional cohort, the rates of
      patients receiving appropriate counselling approximately doubled following the
      introduction of systematic training on smoking cessation and chart labels.
      Extended regular training for physicians on smoking-related issues may have a
      potentially beneficial effect in improving counselling of smokers and meeting the
      global tobacco challenge.

PMID- 20131123
TI  - Impact of international consensus guidelines on antiviral therapy of chronic
      hepatitis C patients in Switzerland.
AB  - AIM OF THE STUDY: To assess the impact of international consensus conference
      guidelines on the attitude of Swiss specialists when facing the decision to treat
      chronic hepatitis C patients. METHODS: Questionnaires focusing on the personal
      situation and treatment decisions were mailed to 165 patients who were newly
      diagnosed with hepatitis C virus (HCV) infection and enrolled into the Swiss
      Hepatitis C Cohort Study during the years 2002-2004. RESULTS: Survey respondents
      (n = 86, 52.1%) were comparable to non-respondents with respect to severity of
      liver disease, history of substance abuse and psychiatric co-morbidities. Seventy
      percent of survey respondents reported having been offered antiviral treatment.
      Patients deferred from treatment had less advanced liver fibrosis, were more
      frequently infected with HCV genotypes 1 or 4 and presented more often with a
      history of depression. There were no differences regarding age, socio-economic
      background, alcohol abuse, intravenous drug abuse or methadone treatment when
      compared with patients to whom treatment was proposed. Ninety percent of eligible
      patients agreed to undergo treatment. Overall, 54.6% of respondents and 78.3% of
      those considered eligible had actually received antiviral therapy by 2007. Ninety
      five percent of patients reported high satisfaction with their own hepatitis C
      management. CONCLUSIONS: Consistent with latest international consensus
      guidelines, patients enrolled in the Swiss Hepatitis C Cohort with a history of
      substance abuse were not withheld antiviral treatment. A multidisciplinary
      approach is warranted to provide antiviral treatment to patients suffering from
      depression.

PMID- 20131124
TI  - Lymphogranuloma venereum in Zurich, Switzerland: Chlamydia trachomatis serovar L2
      proctitis among men who have sex with men.
AB  - BACKGROUND: Whereas until 2003 Lymphogranuloma venereum (LGV) was rare in
      industrialised countries, there have been increasing reports of cases of LGV
      proctitis in men having sex with men (MSM) over the last six years in Europe,
      America and Australia. PATIENTS AND METHODS: After the alarming message from the
      Netherlands in 2003, physicians in a dermatological and STI private clinic in
      Zurich started examining rectal swabs from patients with proctitis for LGV
      serovars of C. trachomatis on a regular basis. A test system based on PCR with
      sequencing and databank comparison was used. Clinical files of all patients with
      proctitis observed in this time period were examined. RESULTS: Since 2003 twelve
      cases of proctitis, all in MSM, caused by the LGV serovar L2 C. trachomatis were
      observed. Of the overall 11 patients the majority were HIV positive and only 2
      were HIV negative. Only one patient reported previous sexual contacts outside
      Europe (Thailand) as the likely place of infection. The clinical presentation was
      characterised by anorectal pain, discharge, tenesmus and change in stool
      frequency. Four patients were successfully treated with a single dose of 1 g
      azithromycin. In all seven cases treated with doxycycline 2 x 100 mg for 10-20
      days clinical cure and a negative PCR result after treatment were observed,
      except for one patient lost to follow-up. CONCLUSIONS: Zurich has not been spared
      by the recent outbreaks of LGV proctitis in MSM. Anorectal LGV infections may
      progress to severe destructive changes, with formation of granulomas, strictures,
      and perirectal abscesses. Increased awareness of this problem and establishment
      of reliable diagnostic tools are required.

PMID- 20131125
TI  - Organ transplantation in Switzerland: impact of the new transplant law on cold
      ischaemia time and organ transports.
AB  - BACKGROUND: On 1 July 2007 a new transplant law came into force in Switzerland.
      The principal item of this new law is the change from centre-oriented allocation
      to patient-oriented national allocation of organs. The aim of the present study
      is to assess the impact on cold ischaemia time (CIT) and transport requirements.
      METHODS: From 1 July 2006 to 30 June 2008 168 brain-dead donors were registered
      by Swisstransplant in Switzerland. Donors have been analysed in a retrospective
      cohort study design. Donor characteristics, transportation requirements and CIT
      were assessed from the Necroreport. RESULTS: 74 donors (44%) were allocated in
      the period before the introduction of the new law (period A) and 94 donors (56%)
      after the new law. Donor characteristics were similar. In period A, 114 organs
      (37.9%) were allocated within the procurement centre, compared to 54 organs
      (15.5%) in period B. Transport time for liver and kidney was remarkably longer in
      period B. Overall, CITs remained largely stable except for a significant increase
      of nearly 115 minutes in the liver graft median CIT (p <0.01). CONCLUSIONS: The
      new Swiss transplant law clearly entails an increase in the frequency of organ
      transports. Overall CIT is not affected. However, liver transplantation is
      afflicted by an increase in transports and CIT. This may affect mid-term outcome
      and should therefore be followed closely.

PMID- 20131126
TI  - Reduction in risk-taking behaviors among MSM in Senegal between 2004 and 2007 and
      prevalence of HIV and other STIs. ELIHoS Project, ANRS 12139.
AB  - An epidemiological survey conducted in Senegal in 2004 among men having sex with
      men (MSM) revealed high HIV prevalence and a high rate of risky behaviors within
      this population. Consequently, several prevention campaigns targeting MSM were
      implemented. A second survey was carried out in 2007 to assess the impact of
      these measures. This paper aims to examine trends in HIV and STI prevalence and
      in sexual behaviors between 2004 and 2007. The two surveys were conducted in four
      urban sites among 440 and 501 MSM--recruited using the snowball sampling method-
      in 2004 and 2007, respectively. A similar methodology was applied for both
      surveys. This consisted of a closed-ended questionnaire concerning socio
      demographic, behavioral, and biomedical information plus a clinical examination
      including urine and blood tests to detect STIs and HIV infection. Between 2004
      and 2007, the frequency of different sexual practices reported by MSM remained
      stable, but condom use for each type of sexual practice rose. The percentage of
      men who reported consistent condom use during previous-month anal sex has
      increased by about 35% (p<0.01). The percentage of men who reported consistent
      condom use during previous-month non-commercial sex with women has increased by
      14% (p<0.01). HIV prevalence remained stable from 22.4% [95% CI: 18.6-26.8] in
      2004 to 21.8% [95% CI: 18.3-25.7] in 2007 (adjusted OR = 1.05, p=0.8). Gonorrhea
      prevalence decreased from 5.5% [95% CI: 3.6-8.3] in 2004 to 2.6% [95% CI: 1.5
      4.5] in 2007 (adjusted OR=0.5, p=0.07). The prevention campaigns, STI and HIV
      care and support programs conducted in Senegal among MSM have been followed by a
      reduction of risk-taking behaviors and STI prevalence among this population.
      Specific targeting of this group within HIV/STI prevention programs seems to be
      effective in decreasing sexual infections.

PMID- 20131127
TI  - Prevalence of depression and anxiety disorders in HIV-positive outpatients in
      rural Tanzania.
AB  - HIV/AIDS is associated with significant mental health morbidity in high-income
      countries, and depression associated with HIV/AIDS has been linked with faster
      disease progression and reduced drug adherence. However, research on mental
      health is scarce in sub-Saharan Africa where infection levels are highest. This
      cross-sectional study of 220 HIV-positive outpatients at a dedicated Tanzanian
      HIV/AIDS care centre assessed sociodemographics, clinical variables and
      prevalence of ICD-10 common mental health diagnoses via a standardised
      psychiatric questionnaire (the Clinical Interview Schedule-Revised). Depression
      or mixed anxiety and depression was identified in 15.5% of subjects, with 4.5%
      suffering from other anxiety disorders. This suggests routine HIV care in sub
      Saharan Africa should include assessment and treatment of mental health issues.

PMID- 20131128
TI  - US Latina age of sexual debut: long-term associations and implications for HIV
      and drug abuse prevention.
AB  - This cross-sectional study explored associations among (a) age of sexual debut;
      (b) drug abuse; and (c) sexual risk behaviors among an urban community-based
      sample of 158 predominantly immigrant, Latina adults. Time in the USA and having
      a mother who used drugs during the participants' childhood or adolescence were
      significantly related to age of sexual debut. In turn, younger ages of sexual
      debut were associated with drug abuse and more sexual risk behaviors (greater
      number of sexual partners, more frequent alcohol and drug use before or during
      sex, greater levels of intoxication from alcohol or drugs during sex).
      Implications for HIV/AIDS and drug abuse clinical services and future research
      with US Latina populations are discussed.

PMID- 20131129
TI  - ABC for AIDS prevention in Guinea: migrant gold mining communities address their
      risks.
AB  - Contrary to expectation when compared with other migrant mining zones of sub
      Saharan Africa, the nation of Guinea has a comparatively low and stable HIV rate.
      In addition, the regions with the largest gold, diamond, and bauxite mining
      operations report the lowest HIV rates within the country. This research set out
      to explain practices and beliefs within gold mining communities near Siguiri,
      Guinea--the highest-producing gold mining zone in the country--that may
      contribute to this phenomenon, particularly as they relate to the Abstinence, Be
      faithful, use a Condom approach to AIDS prevention. Structured interviews on a
      randomly selected sample of 460 adults and regular visitation to 16 pharmacies
      and health clinics within the mining zone yielded data showing that abstinence
      and condom use are minimally practiced for AIDS prevention. Instead, faithfulness
      to partners was overwhelmingly reported as the method of choice for AIDS
      avoidance. In addition, this research explored ways in which local conceptions of
      fidelity differed from those generally understood in other contexts, including
      engagement in short-term marriages at the gold mining sites.

PMID- 20131130
TI  - Racial and ethnic health disparities: evidence of discrimination's effects across
      the SEP spectrum.
AB  - OBJECTIVES: Perceived discrimination is a psychosocial stressor that plays a role
      in explaining racial/ethnic disparities in self-reported physical and mental
      health. The purpose of this paper is: (1) to investigate the association between
      perceived discrimination in receiving healthcare and racial/ethnic disparities in
      self-rated health status, physical, and emotional functional limitations among a
      diverse sample of California adults; (2) to assess whether discrimination effects
      vary by racial/ethnic group and gender; and (3) to evaluate how the effects of
      discrimination on health are manifest across the socioeconomic position (SEP)
      spectrum. DESIGN: Data were drawn from the 2001 California Health Interview
      Survey adult file (n=55,428). The analytic approach employed multivariate linear
      and logistic regressions. Discrimination is qualitatively identified into two
      types: (1) discrimination due to race/ethnicity, language, or accent, and (2)
      other discrimination. RESULTS: Findings show that both types of discrimination
      negatively influenced self-rated health, and were associated with a two to three
      fold odds of limitations in physical and emotional health. Further, these effects
      varied by racial/ethnic group and gender, and the effects were mixed. Most
      notably, for emotional health, racial/ethnic discrimination penalized Latinas
      more than non-Latina Whites, but for physical health, other discrimination was
      less detrimental to Latinas than it was to non-Latina Whites. At higher levels of
      SEP, the effects of racial/ethnic discrimination on self-rated health and other
      discriminations' effects on physical health were attenuated. DISCUSSION: Higher
      SEP may serve as an important mitigator, particularly when comparing the medium
      to the low SEP categories. It is also possible that SEP effects cannot be
      extracted from the relationships of interest in that SEP is an expression of
      social discrimination. In fact, negative health effects associated with
      discrimination are evident across the SEP spectrum. This study highlights the
      complexity of the relationships between discrimination and racial/ethnic
      identity, gender, and SEP.

PMID- 20131131
TI  - Effective quality control of incoming potatoes as an acrylamide mitigation
      strategy for the French fries industry.
AB  - The correlation between sugar levels in raw material (potatoes), brown colouring
      and formation of acrylamide in French fries was investigated. The objective was
      to identify incoming potatoes (raw material) with a high potential for acrylamide
      formation. Ten different potato varieties commonly used in the Western European
      French fries industry were stored at 8 degrees C and samples were taken
      throughout the storage time. The current quality control used in the French fries
      industry for incoming potatoes is poorly correlated with acrylamide in the final
      product (r = 0.74). Changing the quality control parameter from colour to
      reducing sugars in raw material did not improve the correlation (r = 0.72). The
      best correlation was obtained with the Agtron colour measurement after blanching
      and a two-stage frying (r = -0.88). It was concluded that alternative entrance
      control measurements could provide better mitigation of the acrylamide issue in
      French fries from the start of production. These alternatives, however, are less
      cost-effective and more difficult to implement.

PMID- 20131132
TI  - Parents' food choices: obesity among minority parents and children.
AB  - This article examines obesity among minority parents and children in the context
      of culture, socioeconomic status, and the parent-child dyad. Knowing parental
      attitudes about eating habits, food preparation, and dietary guidelines is
      crucial to addressing childhood obesity. Parents of African American, Caribbean,
      and Hispanic descent participated in focus groups to explore their attitudes and
      practices regarding the food choices they make for themselves and their 6- to 12
      year-old children. Cultural identification and time constraints were identified
      as key themes that influence food choice decisions. Several recommendations are
      made for health care practitioners working with families to reduce the incidence
      of obesity.

PMID- 20131133
TI  - Benefits and barriers of pap smear screening: differences in perceptions of
      Vietnamese American women by stage.
AB  - Low participation in Papanicolaou screening among Vietnamese American women
      remains a significant public health problem. This study explored differences in
      the perceived benefits of and barriers to obtaining Papanicolaou smears within
      the framework of the transtheoretical model stages of readiness. A descriptive,
      cross-sectional design with snowball sampling was used to recruit 80 Vietnamese
      American women. The self-administered questionnaire included a Demographic
      Questionnaire, Cervical Cancer Screening Stage Questionnaire, and
      Benefits/Barriers Scale. Results suggest that knowledge of cervical cancer,
      awareness of screening programs, and availability of female physicians play
      important roles in the transition from precontemplation to maintenance within the
      transtheoretical model framework.

PMID- 20131134
TI  - Influential factors of long-term care in a Japanese rural community examined
      through interviews of family caregivers.
AB  - Recent increases in the number of those with health care needs who live at home
      in Japan highlight the importance of maintaining a healthy community environment
      for long-term care. This study characterized continuing long-term home-based care
      for patients with health care needs in a rural community through an examination
      of influential factors, as perceived by family caregivers of patients with care
      needs. Semistructured interviews revealed self-reliance as the most important
      factor. Promoting the quality of a family caregiver's life was also found to be
      important. Family caregiver support is required considering the character of a
      rural community and residents' ideologies.

PMID- 20131135
TI  - Immigrant women's cancer screening behaviors.
AB  - OBJECTIVES: Investigate the relationship between the dependent variable health
      outcome (perceived health status) and the independent variables population
      characteristics, (predisposing, which includes age, acculturation, months in the
      United States; enabling, which includes availability of medical insurance) and
      health behavior (personal health practices, which includes engaging in cancer
      screening of mammography, Pap smear, and breast self-exam) among immigrant women
      from the former Soviet Union. DESIGN: Descriptive correlational design was used
      with Andersen's Behavioral Model as the conceptual framework. SAMPLE: Convenience
      sample of 99 women, 18 years of age and older, was obtained from a community
      center. MEASURES: Demographic Information for Immigrants from the Former Soviet
      Union Survey (DIFSU) and Language, Identity, and Behavior Acculturation Survey
      (LIB) were used to collect data. RESULTS: Younger women were more likely to have
      a Pap smear and consider their health status as good or excellent; those with
      better English language skills were more likely to conduct breast self-exam but
      considered their health status as poor or fair; having insurance was positively
      correlated with having a Pap smear; the longer women were in the United States,
      the more likely they were to receive a mammogram. The model indicated that age
      and language acculturation significantly predicted health status. CONCLUSION:
      Given the incidence of breast cancer in the United States, the results highlight
      women in need of interventions to help them understand the value of cancer
      screening behaviors.

PMID- 20131136
TI  - From Biloxi to Cape Town: curricular integration of service learning.
AB  - Team Reach Out started as a student-initiated service-learning project with the
      goal of providing on-going assistance to the victims of Hurricane Katrina. Four
      years after Hurricane Katrina, Team Reach Out refocused efforts to Cape Town,
      South Africa, where 4 senior nursing students and 1 science student integrated
      their leadership skills with the application of public health knowledge,
      compassion, and concern to work in partnership with several international health
      agencies. This article reviews the service-learning framework, course planning,
      and implementation of a recent service-learning project.

PMID- 20131137
TI  - Meningococcal meningitis: an emerging infectious disease.
AB  - Meningococcal meningitis is a potentially fatal disease which can affect many 15-
      to 24-year-olds and those that are affected could have been protected from the
      disease if they had received the vaccination. The number of reported cases has
      increased during the past decade and account for many preventable deaths.
      Adolescents and young adults account for nearly 30 percent of all cases of
      meningitis in the United States. According to the American College Health
      Association, approximately 100 to 125 cases of meningococcal disease occur on
      college campuses each year and at least 60% of these cases are potentially
      preventable by vaccination. Therefore, it is important to understand the disease
      process, surveillance and diagnosis of the disease, and the need for vaccination
      as a form of prevention.

PMID- 20131139
TI  - Experimental evaluation of oil mists using a semivolatile aerosol dichotomous
      sampler.
AB  - The sampling performance of the semivolatile aerosol dichotomous sampler (SADS)
      was tested and compared with existing vapor and particle sampling methods:
      filtration, electrostatic precipitation, and vapor adsorption. Seven different
      test fluids were used to generate test droplets, and their concentrations and
      composition in each phase were evaluated using gas chromatography. The amount of
      wall loss inside the SADS was also evaluated. Combined vapor and particle
      concentrations for each test aerosol were not statistically different from one
      another as a function of test method. However, the particle concentrations
      estimated using the SADS were statistically higher than those from the other
      methods. In experiments with hexadecane, the particle concentrations estimated
      using the SADS, an electrostatic precipitator, and a glass fiber filter were 2.50
      mg/m3, 0.05 mg/m3, and 0.01 mg/m3, respectively. For commercial metalworking
      fluid (MWF) droplets, compounds having low molecular weight were more prevalent
      in the vapor phase than those compounds with high molecular weight. The
      compositions of the particle phase were similar to those of the original fluids.
      The wall losses of hexadecane and bis(2-ethylhexyl) sebacate (BEHS) were 0.25%
      and 26.5% of combined vapor and particle concentrations in the SADS sampling,
      respectively. Because it can avoid evaporative losses, SADS will sample
      semivolatile aerosols more accurately than common filtration methods and may
      often yield higher particle concentrations than can be measured using the other
      methods.

PMID- 20131140
TI  - Body roll in swimming: a review.
AB  - In this article, we present a critical review of the swimming literature on body
      roll, for the purposes of summarizing and highlighting existing knowledge,
      identifying the gaps and limitations, and stimulating further research. The main
      research findings can be summarized as follows: swimmers roll their shoulders
      significantly more than their hips; swimmers increase hip roll but maintain
      shoulder roll when fatigued; faster swimmers roll their shoulders less than
      slower swimmers during a 200-m swim; roll asymmetries, temporal differences in
      shoulder roll and hip roll, and shoulder roll side dominance exist in front crawl
      swimming, but there is no evidence to suggest that they affect swimming
      performance; and buoyancy contributes strongly to generating body roll in front
      crawl swimming. Based on and stimulated by current knowledge, future research
      should focus on the following areas: calculation of body roll for female swimmers
      and for backstroke swimming; differences in body roll between breathing and non
      breathing cycles; causes of body roll asymmetries and their relation to motor
      laterality; body roll analysis across a wide range of velocities and swimming
      distances; exploration of the association between body roll and the magnitude and
      direction of propulsive/resistive forces developed during the stroke cycle; and
      the influence of kicking actions on the generation of body roll.

PMID- 20131141
TI  - Visuo-motor delay, information-movement coupling, and expertise in ball sports.
AB  - We compared the performance of tennis experts and non-experts using a simulated
      interceptive task, in which the ball could be unexpectedly deviated 400 ms before
      contact. The results showed that experts were more accurate than non-experts when
      intercepting balls that deviated in their trajectory and that this could be
      explained by their shorter visuo-motor delay in adapting their interceptive
      movement. In addition, multiple regression analyses revealed that visuo-motor
      delay was a good predictor of accuracy in this task. Finally, accuracy in the
      simulated interceptive task was shown to be a reasonable predictor of expertise
      in tennis assessed by national ranking. In combination, the present results
      suggest that an important component of expertise in interceptive skills is fast
      information-movement coupling, which corresponds to a reduced delay in
      integrating vision and action. Our findings highlight the potential of the
      virtual interceptive task used here to predict performance in tennis.

PMID- 20131142
TI  - Threshold frequency of an electrically induced cramp increases following a
      repeated, localized fatiguing exercise.
AB  - Though clinical observations and laboratory data provide some support for the
      neuromuscular imbalance theory of the genesis of exercise-associated muscle
      cramps, no direct evidence has been published. The purpose of this study was to
      determine the effect of local muscle fatigue on the threshold frequency of an
      electrically induced muscle cramp. To determine baseline threshold frequency, a
      cramp was electrically induced in the flexor hallucis brevis of 16 apparently
      healthy participants (7 males, 9 females; age 25.1 +/- 4.8 years). The testing
      order of control and fatigue conditions was counterbalanced. In the control
      condition, participants rested in a supine position for 30 min followed by
      another cramp induction to determine post-threshold frequency. In the fatigue
      condition, participants performed five bouts of great toe curls at 60% one
      repetition maximum to failure with 1 min rest between bouts followed immediately
      by a post-threshold frequency measurement. Repeated-measures analysis of variance
      and simple main effects testing showed post-fatigue threshold frequency (32.9 +/-
      11.7 Hz) was greater (P < 0.001) than pre-fatigue threshold frequency (20.0 +/-
      7.7 Hz). An increase in threshold frequency seems to demonstrate a decrease in
      one's propensity to cramp following the fatigue exercise regimen used. These
      results contradict the proposed theory that suggests cramp propensity should
      increase following fatigue. However, differences in laboratory versus clinical
      fatiguing exercise and contributions from other sources, as well as the notion of
      a graded response to fatiguing exercise, on exercise-associated muscle cramp and
      electrically induced muscle cramp should be considered.

PMID- 20131143
TI  - Exercise intensity during wheelchair rugby training.
AB  - The purpose of this study was to determine the ability of individuals with a
      cervical spinal cord injury to achieve and sustain a cardiorespiratory training
      intensity during wheelchair rugby. Nine wheelchair rugby players completed a
      continuous peak exercise test on a SciFit Pro I arm ergometer with stage
      increases each minute to determine peak heart rate and power output.
      Approximately one week after peak exercise testing, heart rate was recorded
      (every 5 s) during three regularly scheduled rugby training sessions. Data were
      analysed to determine the number of continuous minutes that participants spent
      above 70% of heart rate reserve under various rugby training activities. The
      percent of time spent at or above 70% heart rate reserve varied across
      participants and conditions. Continuous pushing was the least variable training
      condition among participants with the sample averaging greater than 73% of time
      above the target heart rate. Scrimmage training was highly variable across
      participants with a range of 0% to 98% of time above the criterion. Results of
      this study indicate that wheelchair rugby training enables some participants to
      reach a training intensity associated with improved cardiorespiratory fitness,
      and that the type (or kind) of training activity dictates the extent to which
      individuals sustain such a threshold.

PMID- 20131144
TI  - Space-time coordination dynamics in basketball: Part 2. The interaction between
      the two teams.
AB  - In this article, we examine the space-time coordination dynamics of two
      basketball teams during competition. We identified six game sequences at random,
      from which the movement data of each player were obtained for analysis of team
      behaviours in both the longitudinal (basket-to-basket) and lateral (side-to-side)
      directions. The central position of a team was measured using its spatial
      (geometric) centre and dispersion using a stretch index, obtained from the mean
      distance of team members from the spatial centre. Relative-phase analysis of the
      spatial centres demonstrated in-phase stabilities in both the longitudinal and
      lateral directions, with more stability in the longitudinal than lateral
      direction. As anticipated, this finding is consistent with the results of an
      analysis of individual playing dyads (see companion article, this issue), as well
      as the more general principle of complex systems conforming to similar
      descriptions at different levels of analysis. Phase relations for the stretch
      index demonstrated in-phase attraction in the longitudinal direction and no
      attraction to any values in the lateral direction. Finally, the difference
      between the two stretch indexes at any instant showed phase transitions between
      two stable patterns when the difference was represented in binary form. This
      result is attributed to the reciprocity between teams in their amounts of
      expansion and contraction when possession of the ball is won and lost.

PMID- 20131145
TI  - Sport commitment among competitive female athletes: test of an expanded model.
AB  - In the present study, we examined an expanded model of sport commitment by adding
      two determinants (perceived costs and perceived competence) and behavioural
      commitment as a consequence of psychological commitment, as well as identifying
      psychological commitment as a mediator of relationships between determinants and
      behavioural commitment. Competitive female gymnasts (N = 304, age 8-18 years)
      completed relevant measures while coaches rated each gymnast's training
      behaviours as an indicator of behavioural commitment. Path analysis revealed that
      the best fitting model was one in which original determinants (enjoyment,
      involvement opportunities, investments, attractive alternatives) and an added
      determinant (perceived costs) predicted psychological commitment, in addition to
      investments and perceived costs directly predicting behavioural commitment. These
      results provide further, but partial, support for the sport commitment model and
      also suggest that additional determinants and behavioural consequences be
      considered in future research.

PMID- 20131146
TI  - Space-time coordination dynamics in basketball: Part 1. Intra- and inter
      couplings among player dyads.
AB  - We examined space-time patterns of basketball players during competition by
      analysing movement data obtained from six game sequences. Strong in-phase
      relations in the longitudinal (basket-to-basket) direction were observed for all
      playing dyads, especially player-opponent dyads matched for playing position,
      indicating that these movements were very constrained by the game demands.
      Similar findings for in-phase relations were observed for the most part in the
      lateral direction, the main exception being dyads comprising the two wing players
      from the same team. These dyads instead demonstrated strong attractions to anti
      phase, a consequence perhaps of seeking to increase and decrease team width in
      tandem. Single instances from select dyads and game sequences demonstrated
      further evidence of phase stabilities and phase transitions on some occasions.
      Together, these findings demonstrate that space-time movement patterns of playing
      dyads in basketball, while unique, nonetheless conform to a uniform description
      in keeping with universal principles of dynamical self-organizing systems as
      hypothesized.

PMID- 20131147
TI  - The effects of plague on the distribution of property: Ivrea, Northern Italy
      1630.
AB  - The demographic effects of the epidemics of plague in Early Modern Europe and
      their economic consequences illuminate the evolution of property structures and
      of wealth distribution during and after a mortality crisis. An analysis of the
      high-quality data available for the Italian city of Ivrea at the time of the 1630
      plague shows the exceptional resilience of property structures. Like the social
      structures of the period, property structures were able to recover quickly,
      informed as they were by the lessons learnt by trial and error by the patrician
      families of the late Middle Ages, whose patrimonies had been badly damaged by the
      Black Death. In a period of recurrent catastrophes that struck European
      populations during the Old Demographic Regime, apparently 'inegalitarian'
      institutions seem to have had long-term 'egalitarian' effects.

PMID- 20131148
TI  - Small group treatments: introduction to special section.

PMID- 20131149
TI  - Predictors of sustained therapeutic change: some thoughts about
      conceptualizations.

PMID- 20131150
TI  - Mediators, moderators, and evidence-based explanation: comment on Blatt et al.

PMID- 20131151
TI  - The impact of the two-configurations model of personality development and
      psychopathology on psychotherapy research: rejoinder to Beutler and Wolf.

PMID- 20131152
TI  - Beyond the tip of the iceberg: exploring the potential of the meaning extraction
      method and aftercare e-mail themes.

PMID- 20131153
TI  - A reaction to "inpatient treatment to online aftercare".

PMID- 20131154
TI  - MEM's search for meaning: a rejoinder.

PMID- 20131156
TI  - How the social brain experiences empathy:  Summary of a gathering.
AB  - Explaining how, and even why, the social brain experiences empathy is a complex
      integrative endeavor that has been explored by scientists of several disciplines
      working with both animal and human subjects. Current thoughts on empathy and its
      connection to behavior-prosocial, altruistic, and cruel alike-were explored by
      scholars in the fields of biology, philosophy, psychology, and anthropology at a
      conference in Chicago. The speakers' individually unique perspectives merged to
      provide an inclusive overview of the biological basis of, and cultural influences
      upon, empathy. The nature of empathy in nonhuman animals, the endocrine
      requirements for empathy,the effects of empathy on moral behavior, the social
      nature of pain, the relation between empathy and altruism,the ethnography of
      empathy, and empathy in the medical setting were discussed. The interdisciplinary
      nature of the conference demonstrated the advantages of communicating findings
      across fields while also delineating the difficulties that can stem from the
      existence of multiple approaches to, and definitions of, empathy. Future progress
      will be aided by working toward common definitions for empathy, sympathy,
      altruism, and so on, in concert with cross-disciplinary dialogues that allow
      practitioners of each discipline to be informed by paradigms and findings from
      complementary disciplines.

PMID- 20131157
TI  - Blood stains--why an absurd policy banning gay men as blood donors has not been
      changed.

PMID- 20131158
TI  - Moral complexity and the delusion of moral purity.

PMID- 20131159
TI  - Transplant tourism in China: a tale of two transplants.
AB  - The use of organs obtained from executed prisoners in China has recently been
      condemned by every major transplant organization. The government of the People's
      Republic of China has also recently made it illegal to provide transplant organs
      from executed prisoners to foreigners transplant tourists. Nevertheless, the
      extreme shortage of transplant organs in the U.S. continues to make organ
      transplantation in China an appealing option for some patients with end-stage
      disease. Their choice of traveling to China for an organ leaves U.S. transplant
      programs with decisions about how to respond to the needs of patients who return
      after transplantation. By discussing two cases that raised this dilemma, we argue
      for upholding medicine's commitments to traditional principles of beneficence and
      nonjudgmental regard in sorting out the policies that a transplant program should
      adopt. We also explain how position statements that aim for the high ground of
      moral purity fail to give appropriate weight to the needs and suffering of
      present and future patients in the U.S. and in China.

PMID- 20131160
TI  - A response to commentaries on "Blood donation, deferral, and discrimination".

PMID- 20131161
TI  - Response to open peer commentaries on "Returning to history: the ethics of
      researching asylum seeker health in Australia".

PMID- 20131162
TI  - The transplant surgeon and transplant tourists: ethical and surgical issues.

PMID- 20131163
TI  - Professional obligation and supererogation with reference to the transplant
      tourist.

PMID- 20131164
TI  - Providing optimal care with dirty hands.

PMID- 20131165
TI  - Professional and public ethics united in condemnation of transplant tourism.

PMID- 20131166
TI  - A modest proposal in response to Rhodes and Schiano.

PMID- 20131167
TI  - Transplant tourism from Taiwan to China: some reflection on professional ethics
      and regulation.

PMID- 20131168
TI  - Transplant tourism from Japan.

PMID- 20131169
TI  - Organ extraction from executed prisoners: Confucian considerations.

PMID- 20131170
TI  - Blood donation, deferral, and discrimination: FDA donor deferral policy for men
      who have sex with men.
AB  - U.S. Food and Drug Administration (FDA) policy prohibits blood donation from men
      who have had sex with men (MSM) even one time since 1977. Growing moral criticism
      claims that this policy is discriminatory, a claim rejected by the FDA. An
      overview of U.S. blood donation, recent donor deferral policy, and the
      conventional ethical debate introduce the need for a different approach to
      analyzing discrimination claims. I draw on an institutional understanding of
      injustice to discern and describe five features of the MSM policy and its FDA
      context that contribute to its discriminatory effect. I note significant
      similarities in the 1980s policy of deferring Haitians, suggesting an historical
      pattern of discrimination in FDA deferral policy. Finally, I point to changes
      needed to move toward a nondiscriminatory deferral policy.

PMID- 20131171
TI  - Sex and blood: a deeper exploration of discrimination in the FDA blood donor
      policy.

PMID- 20131172
TI  - The expressive dimension of donor deferral.

PMID- 20131173
TI  - Blood is a precious resource--does it really matter who donates it?

PMID- 20131174
TI  - Blood donation and its metaphors.

PMID- 20131175
TI  - Returning to history: the ethics of researching asylum seeker health in
      Australia.
AB  - Australia's policy of mandatory indefinite detention of those seeking asylum and
      arriving without valid documents has led to terrible human rights abuses and
      cumulative deterioration in health for those incarcerated. We argue that there is
      an imperative to research and document the plight of those who have suffered at
      the hands of the Australian government and its agents. However, the normal tools
      available to those engaged in health research may further erode the rights and
      well being of this population, requiring a rethink of existing research ethics
      paradigms to approaches that foster advocacy research and drawing on the voices
      of those directly affected, including those bestowed with duty of care for this
      population.

PMID- 20131176
TI  - Repeating history: use and abuse of research findings and the misrepresentation
      of responsibility for health conditions.

PMID- 20131177
TI  - Asylum seekers: subjects or objects of research?

PMID- 20131178
TI  - Consent while hanging from a cliff?

PMID- 20131179
TI  - Ethics and research in the service of asylum seekers.

PMID- 20131180
TI  - From complicity to advocacy: the necessity of refugee research.

PMID- 20131183
TI  - Complimentary roles for N-terminal pro-B-type natriuretic peptide and spirometry
      to assess functional capacity in patients with complex mixed heart valve disease.
AB  - BACKGROUND: Assessing the effects of valvular heart disease on functional
      capacity is important for optimal timing of surgery. AIM: To determine whether N
      terminal pro-B type natriuretic peptide (NT-proBNP) and lung spirometry predict
      maximum oxygen consumption (pVO(2)) on cardio-pulmonary exercise testing in
      patients with mixed heart valve disease. METHODS: Forty-five clinically stable
      patients with moderate-severe stenosis and/or regurgitation of the aortic, mitral
      and/or tricuspid valves were studied. The ability of echocardiography, NT-proBNP,
      forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) to
      predict impaired pVO(2) was determined. RESULTS: On univariate analysis the
      natural logarithm of NT-proBNP explained more of the variation in pVO(2) (r(2) =
      0.40, p < 0.0001) than valve severity score (r(2) = 0.20, p = 0.002), pulmonary
      artery pressure (r(2) = 0.21, p = 0.005), left atrial area index (r(2) = 0.25, p
      = 0.001) or LV ejection fraction (r(2) = 0.02, p = 0.4). Low lean body weight
      (r(2) = 0.21, p = 0.002), FEV1 (r(2) = 0.26, p = 0.0003) and FVC (r(2) = 0.20, p
      = 0.002) were also associated with pVO(2). In multi-variable analysis independent
      determinants of pVO(2) were NT-proBNP (r(2) = 0.27, p = 0.001), FVC (r(2) = 0.20,
      p = 0.0002) and lean body weight (r(2) = 0.23, p = 0.001). NT-proBNP and FVC
      together were better predictors of pVO(2) < 60% (C statistic = 0.83, 95% CI 0.71,
      0.95) than either NT-proBNP (C = 0.80, 95% CI 0.66, 0.94) or FVC (C =0.73, 95% CI
      0.57, 0.89) alone. NT-proBNP, FVC and age also predicted excessive ventilation on
      cardio-pulmonary exercise (combined r(2) = 0.54, p < 0.0001). CONCLUSION: In
      patients with mixed heart valve disease NT-proBNP and spirometry provide a more
      reliable assessment of functional capacity than assessment by echocardiography
      and symptoms alone.

PMID- 20131184
TI  - Plasma adiponectin in patients with acute myocardial infarction treated with
      percutaneous coronary intervention.
AB  - BACKGROUND: Even up-to-date reperfusion therapy using primary percutaneous
      intervention (PCI) in acute myocardial infarction does not result in improvement
      of the left ventricular (LV) function in all patients. Cellular myoblasty, a
      novel method using mononuclear bone marrow cells (BMC), can be applied in the
      infarcted myocardium area to stimulate regeneration and to limit the organ
      damage. However, the impact of intracoronary BMC administration on the effect of
      PCI is not clear. AIM: To assess angiographic outcomes in patients with anterior
      myocardial infarction and LV dysfunction, undergoing intracoronary BMC
      administration after a successful primary PCI. METHODS: The study group consisted
      of 40 patients (mean age 56.2 years) with LV ejection fraction below 40%, in whom
      20 ml of BMC were administered to the infarct-related artery (IRA) distally to
      the occlusion. The control group comprised 25 age- and sex-matched patients with
      similar values of LV ejection fraction undergoing bare metal stenting of IRA
      without BMC administration. Quantitative coronary angiography was performed 6
      months later to assess IRA patency. RESULTS: The reference diameter of the
      stented artery decreased in the study group from 3.22 +/- 0.28 mm to 3.16 +/-
      0.18 mm (p < 0.05) and in the control group from 3.22 +/- 0.31 mm to 3.15 +/-
      0.28 mm (p < 0.082); also in the area of the implanted stent the diameter
      decreased from 3.57 +/- 0.21 mm to 2.96 +/- 0.79 mm in the study group vs. 3.48
      +/- 0.22 mm to 3.01 +/- 0.35 mm in the control group. For lumen diameter measured
      10 mm distally to the stent, the diameter loss was similar in both groups. In 6
      patients from the BMC treated group and in 3 patients from the control group
      there was asymptomatic lumen reduction > 70% (NS). CONCLUSION: The results of our
      study show that BMC administration into IRA is safe. The degree of lumen loss in
      the stent area was larger in the BMC group than in the control group. There was
      no significant difference in the lumen change distally to the stent; the artery
      diameter loss in both groups was similar, and the improvement in LV ejection
      fraction was greater in the BMC-treated group.

PMID- 20131185
TI  - Quality of life in high-risk patients with stable multivessel coronary artery
      disease treated either medically or with coronary artery bypass graft surgery -
      12-month follow-up.
AB  - BACKGROUND: Treatment of chronic diseases, such as atherosclerosis, usually leads
      to significant short-term improvement. Mid- and long-term results are not always
      as satisfactory. That is why improvement of quality of life should be the leading
      qualification criterion for invasive procedures, which sometimes carry a risk of
      complications. AIM: To determine the quality of life in patients with stable,
      multivessel coronary artery disease (MCAD), treated surgically or medically.
      METHODS: The study group comprised 107 patients (pts; 80 males) suffering from
      MCAD, assigned to coronary artery bypass grafting (CABG) (55 pts) or to medical
      treatment alone (52 pts). The mean Gensini score in the whole group was 90 (66
      132). To evaluate quality of life we used a Short Form-36 (SF-36) health status
      survey by the International Quality of Life Assessment Project. RESULTS: During a
      12-month follow-up 9 pts died (6 pts in the medically treated group and 3 in the
      CABG group), all for cardiovascular reasons. Patients treated conservatively were
      more often hospitalised due to angina symptoms (20 vs. 5, p = 0.003). Analysis of
      SF-36 showed that pts treated surgically had better improvement of quality of
      life in comparison with medically treated patients. Significant differences were
      found for physical functioning, bodily pain, vitality, mental health and mental
      component summary. CONCLUSIONS: This study has shown that there is a significant
      difference in health-related quality of life 12 months after CABG surgery and
      medical treatment alone in high-risk patients with MCAD. Surgical treatment
      decreases the number of adverse events, better attenuates of anginal and heart
      failure symptoms, and improves the quality of life, especially the mental
      component. Our results should encouraged selecting patients with advanced
      atherosclerosis for revascularisation procedures, even if there is a very high
      peri-procedural risk.

PMID- 20131186
TI  - Paffenbarger Physical Activity Questionnaire as an additional tool in clinical
      assessment of patients with coronary artery disease treated with angioplasty.
AB  - BACKGROUND: The association between frequency, intensity and duration of physical
      activity and the risk of cardiovascular disease has been investigated in several
      studies. Out of many methods used for assessment of physical activity, a
      questionnaire seems to be a simple and affordable method of assessing the risk of
      coronary artery disease (CAD). However, the number of clinical studies
      investigating the usefulness of physical activity questionnaires is limited. AIM:
      To analyse the usefulness of Paffenbarger Physical Activity Questionnaire (PPAQ)
      in assessment of the correlation between the magnitude of physical activity
      related energy expenditure and physical capacity assessed with treadmill exercise
      test (ET), risk of early onset of major adverse cardiovascular events (MACE) and
      selected haemodynamic parameters in patients with CAD. METHODS: The study group
      consisted of 211 patients aged 34-79 years (mean 59) with CAD, with or without
      previous myocardial infarction (MI). All patients were surveyed using PPAQ at the
      time of PCI and then 6 months later together with ET and echocardiography.
      RESULTS: There was a significant correlation between the value of activity
      related weekly energy expenditure assessed with the PPAQ and selected parameters
      of ET (duration: r = 0.2966, p < 0.0001; METs: r = 0.2221, p < 0.001; VO(2)max: r
      = 0.3075, p < 0.0001; resting HR: r = 0.1615, p < 0.01 and maximal HR: r = 
      0.1475, p < 0.01) and echocardiography (LVESD r = 0.2346, p < 0.0001). After the
      PCI procedure, there was a considerable increase in physical capacity (ET
      duration: 5.82 vs. 7.48 min, p < 0.0001; MET: 7.57 vs. 9.18, p < 0.0001;
      VO(2)max: 29.23 vs. 34.79 ml, p < 0.0001; HRmax: 123 vs. 132 beats/min, p <
      0.0001) and LV function (EF% 51.64 vs. 52.45%, p < 0.01). There was an
      insignificant change in total physical activity-related energy expenditure of low
      intensity (< 4 MET), not exceeding 2000 kcal/week (from 3120.13 to 3139.18
      kcal/week, p > 0.05). Thirty-seven patients with MACE had a trend towards a lower
      value of average weekly energy expenditure than the remaining 174 patients
      (2690.71 vs. 3206.06 kcal/week, NS). CONCLUSIONS: High values of correlation
      coefficients between the questionnaire results and some variables of ET and
      echocardiography examination make the PPAQ a useful tool in clinical studies.

PMID- 20131187
TI  - Availability of automated external defibrillators in the city of Warsaw - status
      for May 2009.
AB  - BACKGROUND: The most frequent cause of sudden cardiac arrest (SCA) is ventricular
      fibrillation and ventricular tachycardia. Despite many efforts the prognosis in
      this patient group is poor. According to the European Resuscitation Council (ERC)
      recommendations, early defibrillation, preferably in the first 3-5 min, is a key
      link in the Chain of Survival after SCA. With an increasing number of available
      automated external defibrillators (AED) time from SCA to defibrillation may be
      reduced, thus resulting in the improvement of patients' prognosis. Therefore, the
      ERC recommends providing AED in public locations with a high incidence of cardiac
      arrests. AIM: Estimation of the availability of AED in the city of Warsaw.
      METHODS: Automated external defibrillators were identified according to the
      information from the City Hall, public services, foundations, companies and own
      research and knowledge. The AED presence was confirmed by phone at the potential
      locations and random locations were visited. RESULTS: By 15 May 2009, 117 AED had
      been reported in 83 points in the city of Warsaw. The number of AED was the
      highest in the Srodmiescie (29) and Wlochy (28) districts. On average, there was
      one AED per 14 706 citizens (0.68 per 10,000 citizens) and per 4.24 km(2) (2.26
      per 10 km(2)). The highest ratio of the number of AED per 10,000 citizens was
      observed in the Wlochy (7.06) and Srodmiescie (2.25) districts, the lowest - in
      the Targowek (0.16), Wawer (0.15) and Bemowo (0.09) districts. The highest ratio
      of the number of AED per 10 km(2) were in the Srodmiescie (18.63), Wlochy (9.78)
      and Zoliborz (5.9) districts, the lowest - in the Wilanow (0.27) and Wawer (0.13)
      districts. CONCLUSIONS: The number of AED in the city of Warsaw should be
      increased, additional demonstrations of AED proper usage and AED promotion should
      be organised. It is necessary to provide easy access to the devices. Significant
      differences in the number of AED can be observed between the districts. Neither
      authorities nor public services are aware of the number of AED in the city of
      Warsaw.

PMID- 20131188
TI  - Plasma NT-proANP in patients with persistent atrial fibrillation who underwent
      successful cardioversion.
AB  - BACKGROUND: Atrial fibrillation (AF) decreases quality of life and significantly
      increases risk of stroke, congestive heart failure and death. Atrial overload and
      stretch also result in increased production of natriuretic peptide type A (ANP).
      The biologically inactive prohormone NT-proANP is released to plasma in the same
      amounts as ANP but it has higher levels in the blood due to decreased degradation
      in vivo. In vitro degradation is also slower and NT-proANP may be an interesting
      alternative for ANP. AIM: To evaluate NT-proANP plasma concentration in patients
      with persistent AF following successful cardioversion. METHODS: The study group
      consisted of 43 patients with persistent AF and normal left ventricular systolic
      function, who underwent successful electrical cardioversion (EC). The control
      group comprised 20 patients with sinus rhythm without a history of AF. Blood
      samples were collected twice, during visits 24 h before and after EC. All
      patients were also examined 30 days after the sinus rhythm recovery. The NT
      proANP concentration was measured using an immunochemical method (ELISA).
      RESULTS: Plasma NT-proANP concentration was significantly increased in patients
      with persistent AF compared to the control group (4.8 +/- 2.9 vs. 2.8 +/- 1.2
      nmol/l, p = 0.004). Plasma NT-proANP level decreased significantly after
      successful cardioversion (to 3.2 +/- 2.4 nmol/l; p < 0.0001). There was no
      correlation between the baseline NT-proANP concentration and sinus rhythm
      maintenance during 30 days after EC. CONCLUSIONS: Plasma NT-proANP concentration
      is higher in patients with persistent AF and normal left ventricular systolic
      function than in patients without arrhythmia. Sinus rhythm recovery due to EC
      leads to a decrease of plasma NT-proANP. The baseline NT-proANP level has no
      prognostic value for prediction of sinus rhythm maintenance during 30 days after
      EC.

PMID- 20131189
TI  - Echocardiographic evaluation of percutaneous valve repair in patients with mitral
      regurgitation using the CARILLON system.
AB  - BACKGROUND: Dilated cardiomyopathy is characterised by significant enlargement of
      cardiac chambers, which can lead to functional mitral regurgitation. Surgery is a
      widely accepted treatment of secondary mitral regurgitation. Conventional cardiac
      surgery has a high procedural risk and therefore new techniques for percutaneous
      repair of mitral valve are being developed. The CARILLON system is one of devices
      that is implanted into the coronary venous system, which enables tension of the
      mitral ring in order to improve coaptation of the leaflets. AIM:
      Echocardiographic analysis of the CARILLON system implantation efficacy evaluated
      directly and one month after implantation. METHODS: The study in included 9
      patients, aged 58.56 +/- 6 years, with severe functional mitral regurgitation,
      who fulfilled the following echocardiographic criteria: large central jet l 4
      cm(2) or l 20% of the left atrium area or wall-impinging eccentric jet reaching
      the pulmonary veins, vena contracta (VC) l 0.30 cm, effective regurgitant orifice
      area (ERO) l 0.2 cm(2), regurgitant volume (RV) l 30 ml or regurgitant fraction
      (RF) > 30%. Exclusion criteria were: concomitant severe tricuspid valve
      insufficiency, significant organic mitral valve pathology, chronic atrial
      fibrillation, foreign body in the coronary sinus, or thrombus in the left atrial
      appendage. The prerequsite for implanting the device was a significant reduction
      in the mitral regurgitation jet observed by transesophageal echo-cadiography
      (TEE), seen during the procedure. After one month, a transthoracic
      echocardiography (TTE) was performed to evaluate mitral regurgitation by
      analysing the same parameters assessed before implanting CARILLON to the coronary
      sinus. RESULTS: A significant improvement of VC after the procedure, in
      comparison to the value before the procedure (0.43 +/- 0.12 vs. 0.66 +/- 0.14 cm,
      p < 0.05), was observed. This improvement was lower one month after the
      implantation of the device (0.35 +/- 0.1 cm, p < 0.005). The ratio of the jet
      area to the left atrial area was reduced from 54.96 +/- 11.18% to 38.57 +/- 9.79%
      (p < 0.005) and sustained after a month at 36.33 +/- 10.15% (p < 0.005). Other
      echocardiographic parameters of evaluation of mitral regurgitation tended to
      improve, however the differences did not reach statistical significance. The ERO
      in subsequent studies was: 0.25 +/- 0.09 cm(2), 0.23 +/- 0.07 cm(2), and 0.24 +/-
      0.07 cm(2), and RV decreased from 33.06 +/- 11.81 ml before the procedure, to
      32.33 +/- 7.84 ml one month after the procedure. CONCLUSIONS: The CARILLON system
      implantation to the coronary venous system in patients with secondary mitral
      regurgitation can lead to the improvement of selected echocardiographic indices
      of mitral regurgitation.

PMID- 20131190
TI  - [Tako-tsubo syndrome - a form of acute coronary syndrome or completely different
      clinical entity - a case report].
AB  - Tako-tsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is a
      temporary left ventricular dysfunction characterised by acute retrosternal rest
      pain, ST - segment elevation, slight elevation of cardiac necrosis markers,
      preferential apical akinesia or hypokinesia with basal hypercontractility in
      echocardiography. Its clinical picture mimics an acute coronary syndrome.
      Coronary angiography reveals normal coronary arteries. The characteristic
      symptoms occur after emotional or physical strain. We report a case of woman
      admitted to the hospital who presented with symptoms of acute coronary syndrome
      with ST - segment elevation. Patient clinical presentation and tests results led
      to a diagnosis of tako-tsubo cardiomyopathy.

PMID- 20131191
TI  - [Left ventricular non-compaction in an infant with congenital heart defect].
AB  - Non-compaction of the left ventricle (NCLV) was categorised as unclassified
      cardiomyopathy by the World Health Organization in 1995. Over the last decade
      this condition has been identified as a distinct form of cardiomyopathy and a
      genetically heterogeneous disorder. Clinically, this may be coupled with the loss
      of contractility, arrhythmia, and thromboembolism. The prognosis in a symptomatic
      patient is generally poor, with progression to chronic heart failure and death,
      including sudden death. We report a case of a child with NCLV and coexisting
      hemodynamic significant ventricular septal defect.

PMID- 20131192
TI  - [Cardiological assessment before pregnancy in a female after surgical correction
      of tetralogy of Fallot - a case report].
AB  - Pregnancy in a female with a history of surgical correction of tetralogy of
      Fallot is an important issue. We describe a cardiological assessment of a 28-year
      old female who underwent echocardiography, exercise test, 24-hour ECG monitoring
      and genetic assessment.

PMID- 20131193
TI  - [The case of surgically treated severe thromboemboic pulmonary hypertension
      developing in the course of recurrent pulmonary embolism].
AB  - A case of a patient with surgically treated progressive thromboembolic pulmonary
      hypertension in the course of recurrent pulmonary embolism resulting from deep
      vein thrombosis is presented. Acute embolic episode seems to have crucial role as
      an initiating factor triggering the cascade of unfavorable changes in pulmonary
      vasculature. The paper stresses the role of systematic clinical and
      echocardiographic control of patients after pulmonary embolism in order to
      diagnose developing complications as soon as possible. It would allow to
      introduce efficient treatment and improve prognosis.

PMID- 20131194
TI  - [Intra-aortic balloon pump as a effective bridging therapy to coronary artery
      bypass grafting in a patient with myocardial infarction and recurrent pulmonary
      edema].
AB  - Intra-aortic balloon pump (IABP) is the most frequently used device for
      mechanical circulation support. We report a case of a 65-year-old female patient
      with myocardial infarction complicated by recurrent pulmonary edema. We decided
      to use long-term IABP despite lack of clear indication for this therapy, what
      enable us to stabilise hemodynamic state of our patient and perform coronary
      artery bypass grafting. Indications for this procedure and risk of long-term
      conterpulsation is discussed.

PMID- 20131195
TI  - [The role of connexin 43 in preconditioning. Impact on mitochondrial function].

PMID- 20131196
TI  - The role of angiotensin receptor 1 blockers in restenosis prevention after
      percutaneous coronary interventions.

PMID- 20131197
TI  - [Electrocardiographic diagnosis of remote myocardial infarction during paced
      cardiac rhythm].

PMID- 20131198
TI  - [Asymptomatic descending aorta dissection after cardiac surgery using extra
      corporeal circulation- a case report].
AB  - Subacute ascending aortic dissection following open heart surgery is a rare but
      potentially fatal complication. It is associated with dilatation of the aortic
      root or cystic medial necrosis. We present associated a case of a 65-year old
      patient with non-fatal ascending aortic dissection after coronary artery bypass
      grafting using extracorporeal circulation.

PMID- 20131199
TI  - ['Protective' stent implantation in a patient with acute coronary syndrome
      without ST segment elevation complicated by in stent thrombosis].

PMID- 20131200
TI  - [Percutaneous coronary intervention in a patient after CABG with acute coronary
      syndrome].

PMID- 20131201
TI  - [Recurrent ventricular tachycardia as a late complication of a cardiac stab
      wound].
AB  - We present a case of a 55-year-old male who suffered from a cardiac stab wound in
      his youth and 38 years later developed unstable sustained ventricular
      tachycardia. Imaging showed presence of a scarf of myocardium which probably
      caused the arrhythmia. Arrhythmia was successfully controlled using combined
      treatment with pharmacotherapy and cardioverter-defibrillator implantation.
      Relapses of ventricular tachycardia treated by appropriate interventions of
      cardioverter-defibrillator occurred when the patient stopped pharmacotherapy and
      experienced great psychic stress.

PMID- 20131202
TI  - Reproducibility of Elecsys anti-TSHR test results in a lot-to-lot comparison.
AB  - Most recently, a new rapid and fully-automated TSH receptor autoantibody (TRAb)
      assay has been established. This assay system uses the M22 human monoclonal
      antibody for competing against the patient's TSH receptor autoantibodies (TRAb)
      to be detected. The aim of our present study was to compare the reproducibility
      of TRAb values based on measurements with different TSH receptor preparations in
      a lot-to-lot comparison. For TRAb values > 2 IU/l the relative differences ranged
      from -9.0 to +10.0%. The mean difference was 0.28 +/- 8%. For TRAb values around
      the cutoff for positivity (1.75 IU/l) a higher range of relative differences from
      -20 up to +15% was obtained. The overall mean of differences was -0.8+/-14%. The
      data clearly demonstrate that the automated TRAb assay has a high stability in
      regard to TSH receptor preparations.

PMID- 20131203
TI  - Familial hyperaldosteronism I-III.
AB  - Primary aldosteronism is the most frequent cause of secondary hypertension. Three
      variants of familial hyperaldosteronism are known today. Early onset hypertension
      and severe target organ damage are hallmarks of the heritable forms. The
      underlying gene defect has already been identified in familial hyperaldosteronism
      type I. In type II and III research is ongoing. A highly variable phenotype often
      precludes the discovery of the familial appearance of these syndromes. Taking a
      sound family history is extremely important to discover the Mendelian pattern of
      inheritance. The identification of affected families is highly rewarding because
      all variants can potentially be cured or at least specifically treated. Testing
      the relatives of an index patient sometimes even allows preemptive treatment.
      However, the availability of specific treatment options necessitates a solid
      differentiation between the three syndromes to avoid unnecessary medical therapy
      or surgery.

PMID- 20131204
TI  - [Life satisfaction and subjective importance of life domains in schizophrenia
      patients: the role of partnership and parenthood].
AB  - OBJECTIVE: The aim is to analyze determinants of subjective quality of life in
      schizophrenia patients. METHODS: Life satisfaction and subjective importance of
      life domains were assessed in 107 patients (FLZ (M)) and compared with the
      general population (n = 2974). RESULTS: Schizophrenia patients experience lower
      levels of life satisfaction as well as less meaningfulness in all life domains.
      According to the range-of-affect hypothesis, patients with low importance ratings
      judged their life satisfaction more homogenously. While the presence of a
      partnership increases life satisfaction, parenthood has only indirect influences
      on satisfaction. CONCLUSION: Psychiatrists should not only explore life
      satisfaction, but also the importance of different life domains and the patient's
      family relations. Supporting beneficial family relations can increase the quality
      of life in schizophrenia patients.

PMID- 20131205
TI  - [A case of cannabis-induced mania].
AB  - We present the course of a mania most likely induced by cannabis in a young
      cannabis-dependent patient, but apart from this, healthy male adult. Mania
      developed in parallel to increasing cannabis inhalation and remitted quickly and
      completely within one week of abstinence without any antimanic medication in a
      protective inpatient setting. Simultaneously, the THC-COOH level decreased in
      serum and urine.

PMID- 20131206
TI  - Reduction of Prepulse Inhibition (PPI) after neonatal excitotoxic lesion of the
      ventral thalamus in pubertal and adult rats.
AB  - BACKGROUND: Growing evidence indicates the role of the thalamus in schizophrenia.
      The ventral part of the thalamus has been investigated in a few post-mortem
      studies, suggesting a possible neurodevelopmental etiology of the reduced neuron
      number. METHODS: Here we adapt a neurodevelopmental animal model, the neonatal
      excitotoxic brain lesion, to the ventral thalamus (VT) of Sprague-Dawley rats. At
      postnatal day (PD) 7 male pups were bilaterally infused into the VT using
      ibotenic acid (IBA) or artificial cerebrospinal fluid. Repeated measurements of
      prepulse inhibition (PPI) of the acoustic startle response, reviewed as a measure
      of sensorimotor gating deficits in neuropsychiatric disorders such as
      schizophrenia, were performed during puberty and adulthood. RESULTS: IBA animals
      showed lower PPI (p<0.001) compared to controls. The extent of VT lesions
      correlated negatively with PPI levels (p<0.001). PPI deficits in IBA animals were
      observed at PD 43 and PPI levels increased significantly after puberty without
      reaching control levels. Acute or subchronic clozapine treatment did not
      significantly restore low PPI in IBA rats. CONCLUSION: The present data suggest
      that the VT may be involved in the PPI deficits observed in schizophrenia.

PMID- 20131207
TI  - Does oral antipsychotic pre-treatment influence outcome of a switch to long
      acting injectable risperidone in patients with schizophrenia?
AB  - INTRODUCTION: The objective of this open-label study was to evaluate treatment
      benefits of risperidone long-acting injectable (RLAI) in patients with
      schizophrenia following direct transition from oral risperidone (RIS) compared
      with transition from other oral second generation antipsychotics. METHODS: Stable
      in- or outpatients (n=206) receiving RIS or OQAZ (olanzapine, quetiapine,
      amisulpride, ziprasidone) were transitioned to RLAI for 12 weeks. The primary
      outcome was the between-group treatment difference in change in PANSS total score
      from baseline to endpoint. Secondary outcomes included health-related quality-of
      life and therapeutic alliance. RESULTS: Mean between-group difference in the
      change in PANSS total score from baseline to endpoint was -6.1 (CI: -17.6, 5.4),
      suggesting greater improvement in OQAZ than RIS patients. Due to the pre
      specified non-inferiority margin of 5.1, it could not be concluded that OQAZ pre
      treatment results in an at least non-inferior PANSS reduction versus RIS pre
      treatment. Patient satisfaction with medication and change in quality-of-life
      subscores showed advantages for OQAZ patients. DISCUSSION: Compared to RIS pre
      treatment, clinically stable patients with schizophrenia who are pre-treated with
      OQAZ might draw a stronger clinical benefit from direct transition to RLAI.

PMID- 20131212
TI  - [Definition and epidemiology of delirium in the elderly].
AB  - Delirium in the elderly is a transient, mostly reversible organic-mental syndrome
      with acute confusion, cognitive impairment, decline of vigilance, increased or
      reduced psychomotor activity and a disturbed sleep-wake-cycle. The etiology of
      delirium is multifactorial. The prevalence of delirium at hospital admission
      ranges from 14 to 24 percent. In addition, the incidence of developing delirium
      during hospitalisation ranges from 5 to 56 percent. Further, a close association
      between delirium and increased mortality rate has been documented. Unfortunately,
      if not specifically looked for, delirium often remains undiscovered by patients,
      physicians and nurses. Recent scientific work demonstrates the important effects
      of delirium both on an individual and societal level, as well as on the health
      care system.

PMID- 20131213
TI  - [Delirium is a very common and life-threatening condition].
AB  - Although a lot is known regarding the epidemiology and aetiology of this
      condition, the pathophysiology of delirium remains poorly understood. Today, the
      leading hypothesized mechanism for the pathogenesis of delirium focuses on a
      central cholinergic deficiency and dopamine excess. Besides, other
      neurotransmitters, such as dopamine, serotonin, norepinephrine, glutamate and
      gamma-aminobutyric acid (GABA) may also contribute to delirium. Moreover,
      cytokines including interleukin-1, interleukin-2, interleukin-6, interferon and
      tumour necrosis factor alpha (TNF-alpha) can lead to an imbalance among the
      different neurotransmitters and thereby lead to an activation of the hypothalamic
      pituitary-adrenocortical axis (HPA axis). The article reviews the current
      pathophysiological findings that may underly delirious states.

PMID- 20131214
TI  - [Diagnosis of delirium].
AB  - Delirium is a clinical diagnosis, which is based on observed disturbances of
      consciousness and cognitive dysfunction. Associated neuropsychiatric and
      psychomotoric symptoms are common. Many elderly delirious patients are
      hypoactive, manifesting a passive demeanor, reduced activity and, in extreme
      cases, stupor and coma. Delirium has an acute onset and a fluctuating course. It
      is usually reversible. It is crucial to examine cognitive functions among elderly
      hospitalized patients, since advanced age and preexisting dementia are important
      risk factors for the development of delirium. In patients with suspected delirium
      there should follow a further diagnostic approach with specific tests, such as
      the Confusion Assessment Method (CAM), a diagnostic tool which has a high
      sensitivity and specifity. Delirium often develops during the course of
      hospitalization, so repeated screening and cognitive testing is needed.
      Predisposing factors need to be identified and treated. The cause of delirium is
      often multifactorial and heterogeneous. Symptoms might be subtle, and clinicians
      frequently under-recognize delirium, so that it is often diagnosed late in its
      course. Especially in the elderly delirium can be the only symptom of an acute
      and severe illness. The typical clinical findings of this illness can be missing.
      The clinical examination and careful use of diagnostic tools is therefore
      essential in the identification and treatment of delirium.

PMID- 20131215
TI  - [Delirium in the intensive care unit].
AB  - The prevalence of delirium in the Intensive Care Unit (ICU) is reported to vary
      from 20 to 80 %. Delirium in the ICU is not only a frightening experience for the
      patient and his or her family, it is also a challenge for the nurses and
      physicians taking care of the patient. Furthermore, it is also associated with
      worse outcome, prolonged hospitalisation, increased costs, long-term cognitive
      impairment and higher mortality rates. Thus, strategies to prevent ICU-delirium
      in addition to the early diagnosis and treatment of delirium are important. The
      pathophysiology of delirium is still incompletely understood, but numerous risk
      factors for the development of delirium have been identified in ICU-patients,
      among which are potentially modifiable factors such as metabolic disturbances,
      hypotension, anaemia, fever and infection. Key factors are the prevention and
      management of common risk factors, including avoiding overzealous sedation and
      analgesia and creating an environment that enhances reintegration. Once delirium
      is diagnosed, treatment consists of the use of typical and atypical
      antipsychotics. Haloperidol is still the drug of choice for the treatment of
      delirium and can be given intravenously in incremental doses of 1 to 2 to 5 (to
      10) mg every 15 - 20 minutes.

PMID- 20131216
TI  - [Drug-induced delirium].
AB  - Drugs have been strongly associated with the development of delirium, and they
      are one of the most easily reversible triggers. In addition to polypharmacy,
      physiological changes with aging including pharmacokinetic and pharmacodynamic
      changes as well as medical co-morbidities can increase the susceptibility to a
      drug induced delirium. Since it is widely accepted that delirium represents
      reversible impairment of cerebral oxidative metabolism and neurotransmission
      [37], it is not surprising that any drug interfering with the function, the
      supply or the use of substrates for neurotransmitter metabolism can cause
      delirium. Drugs with anticholinergic activity, especially those with muscarine
      receptor activity, constitute a considerable risk-group. Many different classes
      of drugs can induce delirium, but several studies have shown that it all comes
      down to the so-called anticholinergic burden, which becomes greater with each
      medication someone takes. In the elderly, polypharmacy and anticholinergic
      toxicity is common. Dementia, e.g. Alzheimer's disease, and, to a lesser extent,
      other chronic brain pathologies, predispose, through reduced integrity of the
      blood-brain barrier function, additionally to the development of delirium.
      Misinterpretation of an adverse drug reaction as another medical condition may
      lead to the prescription of additional medications with their own potential to
      cause side effects. To reduce the morbidity and mortality associated with drug
      induced delirium and also to prevent it, patients' medications should be closely
      monitored. Wherever possible, drugs with anticholinergic effects should be
      avoided in elderly patients, particularly in those suffering from dementia.

PMID- 20131217
TI  - [Delirium and dementia].
AB  - Dementia and delirium are nosologic entities with overlapping presenting
      symptoms. The diagnostic criteria of dementia and of mild cognitive impairment
      conceptualized as prodromal state of dementia-are discussed here and the
      importance of very early diagnosis of cognitive decline and the integration of
      information from informants in the diagnostic process is highlighted. Prominent
      features of vascular dementia and of dementia with Lewy bodies which are
      important for differential diagnosis and therapy are described.

PMID- 20131218
TI  - [Caregiving interventions for non drug-based delirium treatments].
AB  - The prevalence of deliria is increasing exponentially with cumulative age. At the
      University Hospital of Basel 16 % of patients in the 70-79 year age-group, 27 %
      in the 80-89 year age-group and 39 % of the over 90 year old are rated as
      confused and disoriented. Delirious patients suffer from functional decline and
      show a significant higher mortality and institutionalization rate after hospital
      discharge. Nurses have an important role in the multi-component delirium
      management. In addition to the assessment of medication, laboratory parameters,
      oxygenation or urinary excretion, patient-oriented evaluations, pain and stress
      management, assessment of patient perception and communication are of particular
      importance. To meet these goals, nurses need knowledge, education and proof of
      clinical evidence.

PMID- 20131219
TI  - [Drug-based delirium treatment approaches].
AB  - Deliria are a common phenomenon in clinical practise. Predisposing factors are
      age > 70 yr, dementia, substance abuse, and polypharmacy. Precipitating factors
      are just as varied and range from infections, dehydration, and surgical
      intervention to alcohol and drug withdrawal. Anticholinergic and/or dopaminergic
      substances may also trigger deliria. This review presents medical treatment
      options for delirium from current literature and points out substances, which may
      potentially cause deliria.

PMID- 20131220
TI  - [Delirium prevention-the Basel model].
AB  - BACKGROUND: Based on actual evidence, about one third of deliria can be
      prevented. Hereby, preventive measures can address both delirium predisposing as
      well as delirium precipitating factors. METHODS: In 2004 an interdisciplinary
      practice developmental project was developed, implemented and evaluated at the
      University Hospital Basel by action-based research. INTERVENTIONS: Preventive
      measures for delirium were developed, resource nurses trained and a systematic
      delirium screening procedure established. RESULTS: Nurses and doctors highly
      accepted the common approach. The delirium rate declined from 25% to 11%. The
      working load for nurses did not increase on the intervention wards, but decreased
      at night, whereas the night working load increased on the control wards.
      CONCLUSION: An interprofessional and interdisciplinary approach for the
      prevention of delirium has multiple winners: the patient, nurses and doctors.

PMID- 20131221
TI  - Bioremediation of turbid surface water using seed extract from Moringa oleifera
      Lam. (drumstick) tree.
AB  - An indigenous water treatment method uses Moringa oleifera seeds in the form of a
      water-soluble extract in suspension, resulting in an effective natural
      clarification agent for highly turbid and untreated pathogenic surface water.
      Efficient reduction (80.0% to 99.5%) of high turbidity produces an aesthetically
      clear supernatant, concurrently accompanied by 90.00% to 99.99% (1 to 4 log)
      bacterial reduction. Application of this low-cost Moringa oleifera protocol is
      recommended for simplified, point-of-use, low-risk water treatment where rural
      and peri-urban people living in extreme poverty are presently drinking highly
      turbid and microbiologically contaminated water.

PMID- 20131222
TI  - Methods of identifying membrane proteins in spirochetes.
AB  - Bacterial membrane proteins serve vital functions such as nutrient acquisition,
      sensation of the environment, and in gene regulation, secretion, and attachment.
      Proteins on the cell surface are instrumental in host-pathogen interactions and
      many serve as immunogens that confer protection as targets for neutralizing
      antibodies. Integral membrane and lipidated proteins possess hydrophobic domains
      or lipid anchors that interact with the lipid bilayer of cellular membranes,
      allowing the investigator to use hydrophobicity as a means for enrichment. The
      spirochete Borrelia burgdorferi is a Gram negative-like microorganism that
      produces many integral and lipidated proteins, several of which have proven
      important during infection and transmission of the bacterium from the tick vector
      to the mammalian host. Protocols described in this unit for enriching membrane
      proteins have been extensively used by investigators in the study of B.
      burgdorferi, but can be easily adapted to identify and characterize membrane
      associated and surface-exposed proteins associated with other bacteria.

PMID- 20131223
TI  - Sindbis virus: propagation, quantification, and storage.
AB  - The prototype of the Alphaviruses, Sindbis virus, has a broad host range. In
      nature, Sindbis virus shuttles from an insect vector to a vertebrate host and
      back to the insect vector in a complex transmission cycle. Sindbis virus must,
      therefore, be able to replicate in two biochemically and genetically divergent
      hosts, invertebrates and vertebrates. In the laboratory, Sindbis grows to high
      titers in a large variety of cultured cells of both vertebrate and invertebrate
      origin. Sindbis virus is easily titered for infectivity on several mammalian cell
      lines as well as certain mosquito cells. Full-length cDNA clones of several
      strains of Sindbis virus are available from which infectious RNA can be
      synthesized, making possible the genetic manipulation of the virus. Transfection
      of mammalian and insect cells by electroporation has facilitated expression of
      RNA mutants in the cell lines of choice.

PMID- 20131224
TI  - Characterization of the in vitro activity of novel lipoglycopeptide antibiotics.
AB  - The increasing incidence of antibiotic resistance in human pathogens is of
      significant concern. Resistance to the widely-used and highly effective
      glycopeptide antibacterial agent vancomycin, which has been in clinical use for
      over half a century, has emerged in staphylococci and enterococci. This has
      spurred the development of newer glycopeptide agents, some of which show activity
      against vancomycin-resistant organisms. The newer agents currently being
      developed contain lipophilic side-chains, which distinguish them from vancomycin;
      as such, they are categorized as lipoglycopeptides. Oritavancin, telavancin, and
      dalbavancin are lipoglycopeptides in late-stage development to combat Gram
      positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA)
      and vancomycin-resistant enterococci. This unit describes methods that may be
      used to assess the in vitro activities of lipoglycopeptides. The methods include
      susceptibility assays, time-kill and time-kill-synergy assays, inhibition of
      synthesis of macromolecules, membrane perturbation assays, and measurement of
      activity against biofilms.

PMID- 20131225
TI  - Identification of small-molecule scaffolds for p450 inhibitors.
AB  - Mycobacterium tuberculosis cytochrome P450 enzymes (CYP) attract ongoing interest
      for their pharmacological development potential, driving direct screening efforts
      against potential CYP targets with the ultimate goal of developing potent CYP
      specific inhibitors and/or molecular probes to address M. tuberculosis biology.
      The property of CYP enzymes to shift the ferric heme Fe Soret band in response to
      ligand binding provides the basis for an experimental platform for high
      throughput screening (HTS) of compound libraries to select chemotypes with high
      binding affinities to the target. Promising compounds can be evaluated in in
      vitro assays or in vivo disease models and further characterized by x-ray
      crystallography, leading to optimization strategies to assist drug design.
      Protocols are provided for compound library screening, analysis of inhibitory
      potential, and co-crystallization with the target CYP, as well as expression and
      purification of soluble CYP enzymes.

PMID- 20131226
TI  - Cardiovascular disease in patients with inflammatory rheumatic disease is
      associated with up-regulation of markers of inflammation in cardiac microvessels
      and cardiomyocytes.
AB  - OBJECTIVE: Various inflammatory rheumatic diseases (IRDs) are associated with
      increased mortality due to cardiovascular disease. The aim of this study was to
      investigate heart biopsy specimens obtained from patients undergoing coronary
      artery bypass grafting and compare markers of inflammation and endothelial cell
      activation in the cardiac and skeletal muscle of patients with and those without
      IRD. METHODS: Paired biopsy specimens of cardiac and skeletal muscle were
      obtained from 22 consecutive patients with IRD and 8 patients without IRD, all of
      whom were undergoing coronary artery bypass grafting. The biopsy specimens were
      evaluated in a blinded manner by conventional microscopy and digital image
      analysis for cell markers (CD3, CD4, CD8, CD68, CD163, and CD31), HLA (HLA-ABC,
      HLA-DR, and HLA-DQ), adhesion molecules (intercellular adhesion molecule 1 and
      vascular cell adhesion molecule 1), and proinflammatory cytokines (interleukin
      1alpha, interleukin-1beta, and tumor necrosis factor). RESULTS: Patients with IRD
      had significantly higher expression of adhesion molecules, proinflammatory
      cytokines, and all classes of HLA on cardiomyocytes and endothelial cells but no
      increase on mononuclear cells in the myocardium compared with patients without
      IRD. Furthermore, cardiac muscle from patients with IRD displayed significantly
      higher local expression of inflammation and activation of cardiac microvessels
      compared with skeletal muscle from the same patients. CONCLUSION: Patients with
      cardiovascular disease had increased expression of adhesion molecules, HLA, and
      proinflammatory cytokines in heart tissue, indicating local inflammation
      involving microvessels and cardiomyocytes that could play a role in the
      pathogenesis of cardiovascular disease. The more pronounced changes in patients
      with IRD compared with patients without IRD might contribute to the increased
      risk of cardiovascular disease and premature death in patients with IRD.

PMID- 20131227
TI  - Proteomic analysis by two-dimensional electrophoresis to identify the normal
      human chondrocyte proteome stimulated by tumor necrosis factor alpha and
      interleukin-1beta.
AB  - OBJECTIVE: To determine the intracellular proteome of normal human chondrocytes
      stimulated with interleukin-1beta (IL-1beta) and tumor necrosis factor alpha
      (TNFalpha) and to ascertain differences in the protein expression patterns of
      these 2 cytokines. METHODS: Normal human knee cartilage chondrocytes were
      incubated for 48 hours without stimulation or stimulated with IL-1beta (5 ng/ml)
      or with TNFalpha (10 ng/ml). For each culture condition, protein extracts from 4
      normal subjects were pooled and resolved using 2-dimensional electrophoresis.
      Protein spots were visualized with Sypro stain, and qualitative and quantitative
      analyses were performed using PDQuest software. Protein spots were then
      identified by mass spectrometry, using matrix-assisted laser desorption
      ionization-time-of-flight/time-of-flight technology. RESULTS: We identified 37
      spots by mass spectrometry (MS) or by MS/MS, corresponding to 35 different
      proteins. In IL-1beta-stimulated chondrocytes, IL-1beta was found to modulate 22
      proteins, as compared with unstimulated chondrocytes. All of these proteins
      except connective tissue growth factor (CCND2) were up-regulated. Proteins
      involved in cellular metabolism and energy (23%) that were up-regulated or
      induced by IL-1beta included nicotinamide phosphoribosyltransferase, long-chain
      fatty acid-coenzyme A ligase 4, delta-aminolevulinic acid dehydratase,
      triosephosphate isomerase, and an isoform of glyceraldehyde-3-phosphate
      dehydrogenase. In TNFalpha-stimulated chondrocytes, TNFalpha was found to
      modulate 20 proteins, as compared with unstimulated chondrocytes. All of these
      except chitinase 3-like 1 (cartilage glycoprotein 39), proteasome activator
      complex subunit 2, and G3PDH, were up-regulated. Eighteen proteins were
      differently modulated by IL-1beta and TNFalpha. Of these, 45% were related to
      metabolism. CONCLUSION: IL-1beta and TNFalpha induce different profiles of
      intracellular protein expression in healthy human chondrocytes. Most of the
      proteins that are differently regulated are proteins that are implicated in the
      generation of cellular energy and in glycolysis.

PMID- 20131229
TI  - Comparative analysis of gene expression profiles between primary knee
      osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck
      disease.
AB  - OBJECTIVE: To investigate the differences in gene expression profiles of adult
      articular cartilage from patients with Kashin-Beck disease (KBD) versus those
      with primary knee osteoarthritis (OA). METHODS: The messenger RNA expression
      profiles of articular cartilage from patients with KBD, diagnosed according to
      the clinical criteria for KBD in China, were compared with those of cartilage
      from patients with OA, diagnosed according to the Western Ontario and McMaster
      Universities OA Index. Total RNA was isolated separately from 4 pairs of the KBD
      and OA cartilage samples, and the expression profiles were evaluated by Agilent
      4x44k Whole Human Genome density oligonucleotide microarray analysis. The
      microarray data for selected transcripts were confirmed by quantitative real-time
      reverse transcription-polymerase chain reaction (RT-PCR) amplification. RESULTS:
      For 1.2 x 10(4) transcripts, corresponding to 58.4% of the expressed transcripts,
      2-fold changes in differential expression were revealed. Expression levels higher
      in KBD than in OA samples were observed in a mean + or - SD 6,439 + or - 1,041
      (14.6 + or - 2.4%) of the transcripts, and expression levels were lower in KBD
      than in OA samples in 6,147 + or - 1,222 (14.2 + or - 2.8%) of the transcripts.
      After application of the selection criteria, 1.85% of the differentially
      expressed genes (P < 0.001 between groups) were detected. These included 233
      genes, of which 195 (0.4%) were expressed at higher levels and 38 (0.08%) were
      expressed at lower levels in KBD than in OA cartilage. Comparisons of the
      quantitative RT-PCR data supported the validity of our microarray data.
      CONCLUSION: Differences between KBD and OA cartilage exhibited a similar pattern
      among all 4 of the pairs examined, indicating the presence of disease mechanisms,
      mainly chondrocyte matrix metabolism, cartilage degeneration, and apoptosis
      induction pathways, which contribute to cartilage destruction in KBD.

PMID- 20131228
TI  - Blocking ERK-1/2 reduces tumor necrosis factor alpha-induced interleukin-18
      bioactivity in rheumatoid arthritis synovial fibroblasts by induction of
      interleukin-18 binding protein A.
AB  - OBJECTIVE: To examine the mechanism of regulation of interleukin-18 (IL-18)
      bioactivity by IL-18 binding protein (IL-18BP) induction. METHODS: Levels of IL
      18 and IL-18BPa in synovial fluid samples from patients with osteoarthritis (OA)
      or rheumatoid arthritis (RA) were determined by enzyme-linked immunosorbent
      assays (ELISAs), followed by calculation of free IL-18. IL-18 and IL-18BPa
      synthesis in RA synovial fibroblasts that had been treated with proinflammatory
      and antiinflammatory cytokines were assessed by quantitative real-time polymerase
      chain reaction and ELISA, respectively, followed by IL-18 bioactivity
      determination using KG-1 cells. Chemical signaling inhibitors were used for
      determination of the signal transduction pathways involved in IL-18BPa/IL-18
      regulation. Tumor necrosis factor alpha (TNFalpha)-induced caspase 1 activity was
      determined by a colorimetric assay. RESULTS: IL-18BPa was lower in RA synovial
      fluid than in OA synovial fluid (P < 0.05; n = 8), and free IL-18 was higher in
      RA synovial fluid than in OA synovial fluid. TNFalpha induced RA synovial
      fibroblast IL-18BPa and IL-18 in a time-dependent manner (P < 0.05). Evaluation
      of signaling pathways suggested that TNFalpha induced IL-18 production through
      the ERK-1/2, protein kinase Cdelta (PKCdelta), and Src pathways, whereas IL-18BPa
      synthesis was mediated through the NFkappaB, PKC, Src, and JNK pathways.
      Furthermore, addition of exogenous IL-18BPa-Fc reduced the RA synovial fibroblast
      phosphorylation of ERK-1/2 induced by TNFalpha. CONCLUSION: These results suggest
      that IL-18BPa reduces IL-18 bioactivity induced by TNFalpha, by regulating the
      ERK-1/2 pathway in RA synovial fibroblasts. Targeting IL-18 bioactivity by
      induction or addition of IL-18BPa may provide another therapeutic option in the
      management of RA.

PMID- 20131230
TI  - Synovial fibroblasts self-direct multicellular lining architecture and synthetic
      function in three-dimensional organ culture.
AB  - OBJECTIVE: To define the intrinsic capacity of fibroblast-like synoviocytes (FLS)
      to establish a 3-dimensional (3-D) complex synovial lining architecture
      characterized by the multicellular organization of the compacted synovial lining
      and the elaboration of synovial fluid constituents. METHODS: FLS were cultured in
      spherical extracellular matrix (ECM) micromasses for 3 weeks. The FLS micromass
      architecture was assessed histologically and compared with that of dermal
      fibroblast controls. Lubricin synthesis was measured via immunodetection.
      Basement membrane matrix and reticular fiber stains were performed to examine ECM
      organization. Primary human and mouse monocytes were prepared and cocultured with
      FLS in micromass to investigate cocompaction in the lining architecture. Cytokine
      stimuli were applied to determine the capacity for inflammatory architecture
      rearrangement. RESULTS: FLS, but not dermal fibroblasts, spontaneously formed a
      compacted lining architecture over 3 weeks in the 3-D ECM micromass organ
      cultures. These lining cells produced lubricin. FLS rearranged their surrounding
      ECM into a complex architecture resembling the synovial lining and supported the
      survival and cocompaction of monocyte/macrophages in the neo-lining structure.
      Furthermore, when stimulated by cytokines, FLS lining structures displayed
      features of the hyperplastic rheumatoid arthritis synovial lining. CONCLUSION:
      This 3-D micromass organ culture method demonstrates that many of the phenotypic
      characteristics of the normal and the hyperplastic synovial lining in vivo are
      intrinsic functions of FLS. Moreover, FLS promote survival and cocompaction of
      primary monocytes in a manner remarkably similar to that of synovial lining
      macrophages. These findings provide new insight into inherent functions of the
      FLS lineage and establish a powerful in vitro method for further investigation of
      this lineage.

PMID- 20131231
TI  - Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive
      protein are associated with disease activity in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Inflammatory disease activity in patients with systemic lupus
      erythematosus (SLE) may affect the development of atherosclerosis, contributing
      to their increased risk of cardiovascular disease (CVD). This process may be
      mediated by anti-apolipoprotein A-I (anti-Apo A-I), anti-high-density lipoprotein
      (anti-HDL), and anti-C-reactive protein (anti-CRP) autoantibodies. We undertook
      this study to examine whether levels of these antibodies rise in association with
      increased SLE disease activity. METHODS: IgG anti-Apo A-I, anti-HDL, and anti-CRP
      levels were measured in serum from the following groups: 39 patients with
      persistently high disease activity (British Isles Lupus Assessment Group [BILAG]
      A or B score) over the previous 2 years, 42 patients with persistently low
      disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy
      controls, 25 individual patients from whom paired samples (at time of disease
      flare and quiescence) were obtained and compared, 16 patients with newly
      diagnosed lupus nephritis from whom multiple samples were obtained and who were
      followed up prospectively for up to 2 years, and 24 patients with SLE who had
      experienced CVD events. RESULTS: Serum levels of IgG anti-Apo A-I, anti-HDL, and
      anti-CRP were higher in patients with SLE than in controls. Anti-Apo A-I and anti
      HDL levels, but not anti-CRP levels, were higher in patients with persistently
      high disease activity than in those with low disease activity. Mean levels of the
      3 autoantibodies in patients who had experienced CVD events lay between the mean
      levels in the high and low disease activity groups. Only levels of anti-Apo A-I
      were significantly higher in samples obtained from individual patients during
      disease flares than in samples obtained during disease quiescence. In the lupus
      nephritis patients, anti-Apo A-I and anti-HDL levels correlated with serum levels
      of high avidity IgG anti-double-stranded DNA. CONCLUSION: Persistent disease
      activity is associated with a significant increase in IgG anti-Apo A-I and anti
      HDL in patients with SLE.

PMID- 20131232
TI  - The protective effect of antimalarial drugs on thrombovascular events in systemic
      lupus erythematosus.
AB  - OBJECTIVE: The antimalarial medication hydroxychloroquine has been proposed as a
      thromboprotective agent in systemic lupus erythematosus (SLE), but studies thus
      far have been limited by the possibility of confounding by indication. This study
      was conducted to assess whether exposure to antimalarial drugs is associated with
      a decrease in thrombovascular events (TEs) in patients with SLE. METHODS: The
      study was designed as a nested case-control study embedded in an inception cohort
      of patients with SLE, which allowed adjustments for possible confounding by
      calendar year, duration of disease, duration of observation, and severity of
      lupus. After controlling for the possible confounding variables in conditional
      logistic regression models, the use of antimalarial drugs was assessed for its
      effects on the development of TEs in lupus patients. RESULTS: Fifty-four cases of
      TE were identified, and these were matched with 108 control subjects (lupus
      patients without TEs). Univariate analyses identified older age (odds ratio [OR]
      1.04, 95% confidence interval [95%CI] 1.01-1.07) or being older than age 50 years
      (OR 3.5, 95% CI 1.4-8.6) and ever having hypertension (OR 2.5, 95% CI 1.0-5.8) as
      being associated with an increased risk of TEs, whereas use of antimalarial drugs
      (OR 0.31, 95% CI 0.13-0.71) was associated with a decreased risk of TEs. Separate
      analyses were done for arterial and venous TEs, which yielded similar results. In
      multivariate analyses, use of antimalarial drugs (OR 0.32, 95% CI 0.14-0.74) and
      older age (OR 1.04, 95% CI 1.01-1.07) were the only 2 variables that remained
      significant. CONCLUSION: The results from this nested case-control study
      demonstrate that, after accounting for the effects of disease severity, disease
      duration, and calendar year, antimalarial drugs were found to be
      thromboprotective, being associated with a 68% reduction in the risk of all TEs,
      with a range of risk reduction of at least 26% up to as high as 86%.

PMID- 20131233
TI  - Cilostazol enhances apoptosis of synovial cells from rheumatoid arthritis
      patients with inhibition of cytokine formation via Nrf2-linked heme oxygenase 1
      induction.
AB  - OBJECTIVE: To assess the effects of cilostazol in inhibiting proliferation and
      enhancing apoptosis in synovial cells from patients with rheumatoid arthritis
      (RA). METHODS: Synovial cell proliferation was measured by MTT assay. The
      expression of NF-kappaB, IkappaBalpha, Bcl-2, Bax, heme oxygenase 1 (HO-1), and
      Nrf2 was determined by Western blotting. RESULTS: Cilostazol suppressed synovial
      cell proliferation by arresting the G(2)/M phases of the cell cycle, and this was
      reversed by KT5720, an inhibitor of protein kinase A. Cilostazol increased the
      number of TUNEL-positive cells, with increased cytochrome c release and apoptosis
      inducing factor translocation as well as increased caspase 3 activation.
      Cilostazol (10 microM) and cobalt protoporphyrin IX (CoPP) increased HO-1
      messenger RNA and protein expression. These effects were suppressed by zinc
      protoporphyrin IX (ZnPP), an HO-1 inhibitor. Cilostazol and CoPP significantly
      increased IkappaBalpha in the cytosol and decreased NF-kappaB p65 expression in
      the nucleus. Increased expression of tumor necrosis factor alpha (TNFalpha),
      interleukin-1beta (IL-1beta), and IL-6 induced by lipopolysaccharide was
      attenuated by cilostazol and CoPP, and this was reversed by ZnPP. In mice with
      collagen-induced arthritis treated with cilostazol (10 and 30 mg/kg/day), paw
      thickness was decreased with increased apoptotic cells in the joints. In synovial
      cells transfected with small interfering RNA (siRNA) targeting HO-1, cilostazol
      did not suppress expression of TNFalpha, IL-1beta, and IL-6, in contrast to
      findings with negative control cells. Cilostazol- and CoPP-induced HO-1
      expression was diminished in cells transfected with Nrf2 siRNA. CONCLUSION:
      Cilostazol suppressed proliferation of synovial cells from RA patients by
      enhancing apoptosis, and also inhibited cytokine production via mediation of cAMP
      dependent protein kinase activation-coupled Nrf2-linked HO-1 expression.

PMID- 20131234
TI  - Gene expression profiling in autoantibody-positive patients with arthralgia
      predicts development of arthritis.
AB  - OBJECTIVE: To identify molecular features associated with the development of
      rheumatoid arthritis (RA), to understand the pathophysiology of preclinical
      development of RA, and to assign predictive biomarkers. METHODS: The study group
      comprised 109 anti-citrullinated protein antibody (ACPA)- and/or rheumatoid
      factor-positive patients with arthralgia who did not have arthritis but were at
      risk of RA, and 25 patients with RA. The gene expression profiles of blood
      samples obtained from these patients were determined by DNA microarray analysis
      and quantitative polymerase chain reaction. RESULTS: In 20 of the 109 patients
      with arthralgia who were at risk of RA, arthritis developed after a median of 7
      months. Gene expression profiling of blood cells revealed heterogeneity among the
      at-risk patients, based on differential expression of immune-related genes. This
      report is the first to describe gene signatures relevant to the development of
      arthritis. Signatures significantly associated with arthritis development were
      involved in interferon (IFN)-mediated immunity, hematopoiesis, and
      chemokine/cytokine activity. Logistic regression analysis revealed that the odds
      ratio (OR) for developing arthritis within 12 months was 21.0 (95% confidence
      interval [95% CI] 2.8-156.1 [P = 0.003]) for the subgroup characterized by
      increased expression of genes involved in IFN-mediated immunity and/or
      cytokine/chemokine-activity. Genes involved in B cell immunology were associated
      with protection against progression to arthritis (OR 0.38, 95% CI 0.21-0.70 [P =
      0.002]). These processes were reminiscent of those in patients with RA, implying
      that the preclinical phase of disease is associated with features of established
      disease. CONCLUSION: The results of this study indicate that IFN-mediated
      immunity, hematopoiesis, and cell trafficking specify processes relevant to the
      progression of arthritis independent of ACPA positivity. These findings strongly
      suggest that certain gene signatures have value for predicting the progression to
      arthritis, which will pave the way to preventive medicine.

PMID- 20131235
TI  - Trefoil factor 3 is induced during degenerative and inflammatory joint disease,
      activates matrix metalloproteinases, and enhances apoptosis of articular
      cartilage chondrocytes.
AB  - OBJECTIVE: Trefoil factor 3 (TFF3, also known as intestinal trefoil factor) is a
      member of a family of protease-resistant peptides containing a highly conserved
      motif with 6 cysteine residues. Recent studies have shown that TFF3 is expressed
      in injured cornea, where it plays a role in corneal wound healing, but not in
      healthy cornea. Since cartilage and cornea have similar matrix properties, we
      undertook the present study to investigate whether TFF3 could induce anabolic
      functions in diseased articular cartilage. METHODS: We used reverse transcriptase
      polymerase chain reaction, Western blot analysis, and immunohistochemistry to
      measure the expression of TFF3 in healthy articular cartilage, osteoarthritis
      (OA)-affected articular cartilage, and septic arthritis-affected articular
      cartilage and to assess the effects of cytokines, bacterial products, and
      bacterial supernatants on TFF3 production. The effects of TFF3 on matrix
      metalloproteinase (MMP) production were measured by enzyme-linked immunosorbent
      assay, and effects on chondrocyte apoptosis were studied by caspase assay and
      annexin V assay. RESULTS: Trefoil factors were not expressed in healthy human
      articular cartilage, but expression of TFF3 was highly up-regulated in the
      cartilage of patients with OA. These findings were confirmed in animal models of
      OA and septic arthritis, as well as in tumor necrosis factor alpha- and
      interleukin-1beta-treated primary human articular chondrocytes, revealing
      induction of Tff3/TFF3 under inflammatory conditions. Application of the
      recombinant TFF3 protein to cultured chondrocytes resulted in increased
      production of cartilage-degrading MMPs and increased chondrocyte apoptosis.
      CONCLUSION: In this study using articular cartilage as a model, we demonstrated
      that TFF3 supports catabolic functions in diseased articular cartilage. These
      findings widen our knowledge of the functional spectrum of TFF peptides and
      demonstrate that TFF3 is a multifunctional trefoil factor with the ability to
      link inflammation with tissue remodeling processes in articular cartilage.
      Moreover, our data suggest that TFF3 is a factor in the pathogenesis of OA and
      septic arthritis.

PMID- 20131236
TI  - Should antibodies to high-density lipoprotein cholesterol and its components be
      measured in all systemic lupus erythematosus patients to predict risk of
      atherosclerosis?

PMID- 20131237
TI  - Differential expression of protease-activated receptors in monocytes from
      patients with primary antiphospholipid syndrome.
AB  - OBJECTIVE: To investigate the expression of protease-activated receptors (PARs),
      their potential regulation by anticardiolipin antibodies (aCL), and their
      association with the expression of other molecules relevant to thrombosis in
      monocytes obtained from 62 patients with primary antiphospholipid syndrome (APS).
      METHODS: Monocytes were isolated from peripheral blood mononuclear cells by
      magnetic depletion of nonmonocytes. Expression of tissue factor (TF) and PARs 1-4
      genes was measured by quantitative real-time reverse transcription-polymerase
      chain reaction. Cell surface TF and PARs 1-4 expression was analyzed by flow
      cytometry. For in vitro studies, purified normal monocytes were incubated with
      purified APS patient IgG, normal human serum IgG, or lipopolysaccharide, in the
      presence or absence of specific monoclonal antibodies anti-PAR-1 (ATAP2) or anti
      PAR-2 (SAM11) to test the effect of blocking the active site of PAR-1 or PAR-2.
      RESULTS: Analysis of both mRNA and protein for the 4 PARs revealed significantly
      increased expression of PAR-2 as compared with the control groups. PAR-1 was
      significantly overexpressed in APS patients with thrombosis and in the control
      patients with thrombosis but without APS. PAR-3 expression was not significantly
      altered. PAR-4 expression was absent in all groups analyzed. In addition, we
      demonstrated a correlation between the levels of PAR-2 and the titers of IgG aCL,
      as well as parallel behavior of TF and PAR-2 expression. In vitro, IgG from APS
      patients significantly increased monocyte expression of PAR-1 and PAR-2.
      Inhibition studies suggested that there was direct cross-talk between TF and PAR
      2, such that inhibition of PAR-2 prevented the aCL-induced expression of TF.
      CONCLUSION: These results provide the first demonstration of increased expression
      of PARs in monocytes from patients with APS. Thus, PAR antagonists might have
      therapeutic potential as antithrombotic agents in APS.

PMID- 20131238
TI  - Antimalarial treatment may have a time-dependent effect on lupus survival: data
      from a multinational Latin American inception cohort.
AB  - OBJECTIVE: To evaluate the beneficial effect of antimalarial treatment on lupus
      survival in a large, multiethnic, international longitudinal inception cohort.
      METHODS: Socioeconomic and demographic characteristics, clinical manifestations,
      classification criteria, laboratory findings, and treatment variables were
      examined in patients with systemic lupus erythematosus (SLE) from the Grupo
      Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis
      of SLE, according to the American College of Rheumatology criteria, was assessed
      within 2 years of cohort entry. Cause of death was classified as active disease,
      infection, cardiovascular complications, thrombosis, malignancy, or other cause.
      Patients were subdivided by antimalarial use, grouped according to those who had
      received antimalarial drugs for at least 6 consecutive months (user) and those
      who had received antimalarial drugs for <6 consecutive months or who had never
      received antimalarial drugs (nonuser). RESULTS: Of the 1,480 patients included in
      the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean
      duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in
      89 patients (6.0%). A lower mortality rate was observed in antimalarial users
      compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had
      received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925
      (81.1%) for >2 years. Mortality rates among users by duration of antimalarial
      treatment (per 1,000 person-months of followup) were 3.85 (95% confidence
      interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37
      0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18
      4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox
      regression model, antimalarial use was associated with a 38% reduction in the
      mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). CONCLUSION: Antimalarial
      drugs were shown to have a protective effect, possibly in a time-dependent
      manner, on SLE survival. These results suggest that the use of antimalarial
      treatment should be recommended for patients with lupus.

PMID- 20131239
TI  - Association of the FAM167A-BLK region with systemic sclerosis.
AB  - OBJECTIVE: An association of single-nucleotide polymorphisms (SNPs) in the
      FAM167A (previously referred to as C8orf13)-BLK region with systemic lupus
      erythematosus (SLE) has been demonstrated in Caucasians and in Asians. Recent
      studies have shown that many genes, including IRF5, STAT4, and PTPN22, are shared
      susceptibility genes in multiple autoimmune diseases. We undertook the current
      study to examine whether the FAM167A-BLK region is also associated with
      susceptibility to systemic sclerosis (SSc). METHODS: Japanese patients with SSc
      (n = 309) and healthy controls (n = 769) were enrolled in a 2-tiered case-control
      association study. In tier 1, 124 patients and 412 controls were tested to
      determine association of 16 tag SNPs encompassing the FAM167A-BLK region with
      SSc. In tier 2, an additional 185 patients and 357 controls were analyzed for SNP
      rs13277113. RESULTS: Two haplotype blocks that correspond approximately to
      FAM167A and BLK were observed. In tier 1 of the study, the rs13277113A allele in
      the BLK block exhibited the most significant association with SSc after
      correction for multiple testing (permutated P = 0.024). Two SNP haplotypes formed
      by rs13277113 and the most significant SNP in the FAM167A block did not exhibit
      stronger association. When samples from tier 1 and tier 2 were combined, the
      rs13277113A allele was significantly associated with SSc (odds ratio 1.45 [95%
      confidence interval 1.17-1.79], P = 6.1 x 10(-4)). Association or a tendency
      toward association of rs13277113A with SSc was observed regardless of a patient's
      autoantibody profile or whether a patient had diffuse cutaneous or limited
      cutaneous SSc. CONCLUSION: Our findings indicate that the rs13277113A allele is
      associated not only with SLE but also with SSc and that the FAM167A-BLK region is
      a common genetic risk factor for both SLE and SSc.

PMID- 20131240
TI  - Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and
      murine models of rheumatoid arthritis and inhibit toll-like receptors.
AB  - OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs), in addition to their
      antidepressant effects, have been reported to have antiinflammatory effects. The
      aim of this study was to assess the antiarthritic potential of 2 SSRIs,
      fluoxetine and citalopram, in murine collagen-induced arthritis (CIA) and in a
      human ex vivo disease model of rheumatoid arthritis (RA). METHODS: Following
      therapeutic administration of SSRIs, paw swelling was assessed and clinical
      scores were determined daily in DBA/1 mice with CIA. Joint architecture was
      examined histologically at the end of the treatment period. Cultures of human RA
      synovial membranes were treated with SSRIs, and cytokine production was measured.
      Toll-like receptor (TLR) function was examined in murine and human macrophages,
      human B cells, and human fibroblast-like synovial cells treated with SSRIs.
      RESULTS: Both SSRIs significantly inhibited disease progression in mice with CIA,
      with fluoxetine showing the greatest degree of efficacy at the clinical and
      histologic levels. In addition, both drugs significantly inhibited the
      spontaneous production of tumor necrosis factor, interleukin-6, and interferon
      gamma-inducible protein 10 in human RA synovial membrane cultures. Fluoxetine and
      citalopram treatment also inhibited the signaling of TLRs 3, 7, 8, and 9,
      providing a potential mechanism for their antiinflammatory action. CONCLUSION:
      Fluoxetine and citalopram treatment selectively inhibit endosomal TLR signaling,
      ameliorate disease in CIA, and suppress inflammatory cytokine production in human
      RA tissue. These data highlight the antiarthritic potential of the SSRI drug
      family and provide further evidence of the involvement of TLRs in the
      pathogenesis of RA. The SSRIs may provide a template for potential antiarthritic
      drug development.

PMID- 20131241
TI  - Endothelin 1 contributes to the effect of transforming growth factor beta1 on
      wound repair and skin fibrosis.
AB  - OBJECTIVE: To characterize the pathways induced by transforming growth factor
      beta1 (TGFbeta1) that lead to the expression of endothelin 1 (ET-1) in human
      dermal fibroblasts, and to study the effects of TGFbeta1 and ET-1 on the
      acquisition of a profibrotic phenotype and assess the contribution of the
      TGFbeta1/ET-1 axis to skin wound healing and fibrosis in vivo. METHODS: The
      mechanism of induction of ET-1 expression by TGFbeta1 and its effect on the
      expression of alpha-smooth muscle actin and type I collagen were studied in human
      dermal fibroblasts, in experiments involving the TGFbeta receptor inhibitor
      GW788388 and the ET receptor antagonist bosentan, by real-time reverse
      transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent
      assay, immunofluorescence, Western blotting, and promoter/reporter transient
      transfection analyses. Experiments assessing dermal wound healing in mice were
      performed with adenovirus-driven overexpression of active TGFbeta1 and ET-1, with
      or without treatment with bosentan. The contributions of TGFbeta1 and ET-1 to the
      fibrotic response were also assessed in a mouse model of bleomycin-induced skin
      fibrosis, by histologic, immunohistochemical, RT-PCR, and protein analyses.
      RESULTS: TGFbeta1 induced ET-1 expression in human dermal fibroblasts through
      Smad- and activator protein 1/JNK-dependent signaling. The ability of TGFbeta1 to
      induce the expression of profibrotic genes was dependent on ET-1. Adenovirus
      mediated overexpression of TGFbeta1 and ET-1 in mouse skin was associated with
      accelerated wound closure, increased fibrogenesis, and excessive scarring.
      Treatment with bosentan prevented the effects of TGFbeta1. In the bleomycin
      induced fibrosis model, treatment with GW788388 and bosentan prevented the
      fibrotic response. CONCLUSION: Our results strongly support the notion that the
      TGFbeta1/ET-1 axis has a role in wound repair and skin fibrosis. ET-1 receptor
      antagonists, such as bosentan, may represent a useful therapeutic tool in the
      treatment of excessive scarring and fibrosis-related diseases.

PMID- 20131242
TI  - Rituximab monotherapy, rather than rituximab plus antiviral drugs, for initial
      treatment of severe hepatitis C virus-associated mixed cryoglobulinemia syndrome:
      comment on the article by Terrier et al.

PMID- 20131243
TI  - Sex differences of chondrogenic progenitor cells in late stages of
      osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA), a mainly degenerative disease, is known to be
      multifactorial in origin. Gene expression patterns vary between populations and
      sexes. Sex hormone receptors have been described in the cartilage tissue of
      animals and humans. We undertook this study to determine whether the regenerative
      potential of chondrogenic progenitor cells (CPCs) present in the arthritic tissue
      during the late stages of human OA might also be subject to sex-specific
      differences and influenced by sex steroids. METHODS: We analyzed sex-specific
      differences in the regenerative potential of CPCs and the involvement of sex
      hormones in vitro in cartilage samples from patients with late-stage knee OA,
      using electrochemiluminescence immunoassay, microarray analysis, real-time
      reverse transcription-polymerase chain reaction, immunohistochemistry, Western
      blot analysis, fluorescence-activated cell sorting, and cell culture. RESULTS: We
      detected expression of estrogen and testosterone in the OA synovial fluid as well
      as CPCs positive for estrogen receptor alpha (ERalpha), ERbeta, and androgen
      receptor. Both hormones influenced the expression of all 3 receptor genes as well
      as the chondrogenic potential of CPCs by regulating gene expression of Sox9,
      Runx2, type II collagen, and type I collagen. We found regulatory effects on the
      collagens via Sox9 and Runx2 as well as regulatory effects independent of these
      transcription factors. These effects were sex-specific and relied on hormone
      concentrations. CONCLUSION: Physiologic concentrations of testosterone in men and
      premenopausal concentrations of estrogen in women have a positive effect on the
      chondrogenic potential of CPCs in vitro. Therefore, strategies of hormone
      replacement in the synovial fluid of women and men might have beneficial effects
      on the regenerative potential of arthritic cartilage tissue in late stages of
      human OA.

PMID- 20131244
TI  - Mediation of nonerosive arthritis in a mouse model of lupus by interferon-alpha
      stimulated monocyte differentiation that is nonpermissive of osteoclastogenesis.
AB  - OBJECTIVE: In contrast to rheumatoid arthritis (RA), the joint inflammation
      referred to as Jaccoud's arthritis that occurs in systemic lupus erythematosus
      (SLE) is nonerosive. Although the mechanism responsible is unknown, the
      antiosteoclastogenic cytokine interferon-alpha (IFNalpha), whose transcriptome is
      present in SLE monocytes, may be responsible. This study was undertaken to
      examine the effects of IFNalpha and lupus on osteoclasts and erosion in the (NZB
      x NZW)F(1) mouse model of SLE with K/BxN serum-induced arthritis. METHODS:
      Systemic IFNalpha levels in (NZB x NZW)F(1) mice were elevated by administration
      of AdIFNalpha. SLE disease was marked by anti-double-stranded DNA (anti-dsDNA)
      antibody titer and proteinuria, and Ifi202 and Mx1 expression represented the
      IFNalpha transcriptome. Microfocal computed tomography was used to evaluate bone
      erosions. Flow cytometry for CD11b and CD11c was used to evaluate the frequency
      of circulating osteoclast precursors (OCPs) and myeloid dendritic cells (DCs) in
      blood. RESULTS: Administration of AdIFNalpha to (NZB x NZW)F(1) mice induced
      osteopetrosis. (NZB x NZW)F(1) mice without autoimmune disease were fully
      susceptible to focal erosions in the setting of serum-induced arthritis. However,
      (NZB x NZW)F(1) mice with high anti-dsDNA antibody titers and the IFNalpha
      transcriptome were protected against bone erosions. AdIFNalpha pretreatment of
      NZW mice before K/BxN serum administration also resulted in protection against
      bone erosion (r(2) = 0.4720, P < 0.01), which was associated with a decrease in
      the frequency of circulating CD11b+CD11c- OCPs and a concomitant increase in the
      percentage of CD11b+CD11c+ cells (r(2) = 0.6330, P < 0.05), which are phenotypic
      of myeloid DCs. CONCLUSION: These findings suggest that IFNalpha in SLE shifts
      monocyte development toward myeloid DCs at the expense of osteoclastogenesis,
      thereby resulting in decreased bone erosion.

PMID- 20131245
TI  - Intracellular Na(+) and Ca(2+) modulation increases the tensile properties of
      developing engineered articular cartilage.
AB  - OBJECTIVE: Significant collagen content and tensile properties are difficult to
      achieve in tissue-engineered articular cartilage. The aim of this study was to
      investigate whether treating developing tissue-engineered cartilage constructs
      with modulators of intracellular Na(+) or Ca(2+) could increase collagen
      concentration and construct tensile properties. METHODS: Inhibitors of Na(+) ion
      transporters and stimulators of intracellular Ca(2+) were investigated for their
      ability to affect articular cartilage development in a scaffoldless, 3
      dimensional chondrocyte culture. Using a systematic approach, we applied ouabain
      (Na(+)/K(+)-ATPase inhibitor), bumetanide (Na(+)/K(+)/2Cl(-) tritransporter
      inhibitor), histamine (cAMP activator), and ionomycin (a Ca(2+) ionophore) to
      tissue-engineered constructs for 1 hour daily on days 10-14 of culture and
      examined the constructs at 2 weeks or 4 weeks. The gross morphology, biochemical
      content, and compressive and tensile mechanical properties of the constructs were
      assayed. RESULTS: The results of these experiments showed that 20 microM ouabain,
      0.3 microM ionomycin, or their combination increased the tensile modulus by 40
      95% compared with untreated controls and resulted in an increased amount of
      collagen normalized to construct wet weight. In constructs exposed to ouabain,
      the increased percentage of collagen per construct wet weight was secondary to
      decreased glycosaminoglycan production on a per-cell basis. Treatment with 20
      microM ouabain also increased the ultimate tensile strength of neo-tissue by 56
      86% at 4 weeks. Other construct properties, such as construct growth and type I
      collagen production, were affected differently by Na(+) modulation with ouabain
      versus Ca(2+) modulation with ionomycin. CONCLUSION: These data are the first to
      show that treatments known to alter intracellular ion concentrations are a viable
      method for increasing the mechanical properties of engineered articular cartilage
      and identifying potentially important relationships to hydrostatic pressure
      mechanotransduction. Ouabain and ionomycin may be useful pharmacologic agents for
      increasing tensile integrity and directing construct maturation.

PMID- 20131246
TI  - Effectiveness of rituximab treatment in primary Sjogren's syndrome: a randomized,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To study the efficacy and safety of B cell depletion with rituximab, a
      chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary
      Sjogren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial.
      METHODS: Patients with active primary SS, as determined by the revised American
      European Consensus Group criteria, and a rate of stimulated whole saliva
      secretion of > or =0.15 ml/minute were treated with either rituximab (1,000 mg)
      or placebo infusions on days 1 and 15. Patients were assigned randomly to a
      treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at
      5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole
      saliva flow rate, while secondary end points included functional, laboratory, and
      subjective variables. RESULTS: Thirty patients with primary SS (29 female) were
      randomly allocated to a treatment group. The mean +/- SD age of the patients
      receiving rituximab was 43 +/- 11 years and the disease duration was 63 +/- 50
      months, while patients in the placebo group were age 43 +/- 17 years and had a
      disease duration of 67 +/- 63 months. In the rituximab group, significant
      improvements, in terms of the mean change from baseline compared with that in the
      placebo group, were found for the primary end point of the stimulated whole
      saliva flow rate (P = 0.038 versus placebo) and also for various laboratory
      parameters (B cell and rheumatoid factor [RF] levels), subjective parameters
      (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS]
      scores for sicca symptoms), and extraglandular manifestations. Moreover, in
      comparison with baseline values, rituximab treatment significantly improved the
      stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g.,
      B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland
      function on the lissamine green test, MFI scores, Short Form 36 health survey
      scores, and VAS scores for sicca symptoms). One patient in the rituximab group
      developed mild serum sickness-like disease. CONCLUSION: These results indicate
      that rituximab is an effective and safe treatment strategy for patients with
      primary SS.

PMID- 20131248
TI  - HLA-B27 heavy chains distinguished by a micropolymorphism exhibit differential
      flexibility.
AB  - OBJECTIVE: Although the products of the HLA subtypes B*2705 and B*2709 differ
      only in residue 116 (Asp versus His) within their peptide-binding grooves, they
      are differentially associated with inflammatory rheumatic diseases such as
      ankylosing spondylitis (AS): B*2705 occurs in AS patients, whereas B*2709 is only
      rarely encountered. The reasons for this distinct association are still unclear
      but could include subtype-specific conformational and dynamic properties of these
      antigens. The present study was undertaken to investigate structural and dynamic
      differences between B*2705 and B*2709 and their possible relationship to subtype
      specific disease association. METHODS: The membrane-distal segments of the B*2705
      and B*2709 heavy chains were expressed in vitro and reconstituted together with
      beta(2)-microglobulin and a peptide. HLA-B27 complexes loaded with 2 self
      peptides (TIS [RRLPIFSRL] and pVIPR [RRKWRRWHL]) and a sequence-related viral
      peptide (pLMP2 [RRRWRRLTV]) were studied by isotope-edited infrared spectroscopy
      to detect differences in their structure and flexibility at physiologic
      temperature. RESULTS: Our analyses revealed the existence of subtype-specific
      conformational differences between the 2 HLA-B27 heavy chains at physiologic
      temperature, which are undetectable using x-ray crystallography. Irrespective of
      the bound peptide, the heavy chain of the B*2705 complex exhibited higher
      conformational flexibility than the B*2709 heavy chain. CONCLUSION: The present
      study demonstrates the existence of previously undetected systematic
      conformational and dynamic differences between the heavy chains of the 2 HLA-B27
      subtypes. Since effector cell recognition of cells expressing HLA antigens is
      dependent on the dynamic properties of the interacting cell surface molecules,
      this HLA-B27 subtype-specific heavy chain flexibility could have a role in the
      distinct association of HLA-B27 subtypes with spondylarthritides.

PMID- 20131247
TI  - Fox-2 protein regulates the alternative splicing of scleroderma-associated lysyl
      hydroxylase 2 messenger RNA.
AB  - OBJECTIVE: Scleroderma (systemic sclerosis [SSc]) is a complex connective tissue
      disorder characterized by hardening and thickening of the skin. One hallmark of
      scleroderma is excessive accumulation of collagen accompanied by increased levels
      of pyridinoline collagen crosslinks derived from hydroxylysine residues in the
      collagen telopeptide domains. Lysyl hydroxylase 2 (LH2), an important
      alternatively spliced enzyme in collagen biosynthesis, acts as a collagen
      telopeptide hydroxylase. Changes in the pattern of LH2 alternative splicing,
      favoring increased inclusion of the alternatively spliced LH2 exon 13A, thereby
      increasing the levels of the long transcript of LH2 (LH2[long]), are linked to
      scleroderma disease. This study was undertaken to examine the role played by RNA
      binding protein Fox-2 in regulating exon 13A inclusion, which leads to the
      generation of scleroderma-associated LH2(long) messenger RNA (mRNA). METHODS:
      Phylogenetic sequence analysis of introns flanking exon 13A was performed. A
      tetracycline-inducible system in T-Rex 293 cells was used to induce Fox-2
      protein, and endogenous LH2(long) mRNA was determined by reverse transcriptase
      polymerase chain reaction. An LH2 minigene was designed, validated, and used in
      Fox-2 overexpression and mutagenesis experiments. Knockdown of Fox-2 was
      performed in mouse embryonic fibroblasts and in fibroblasts from SSc patients.
      RESULTS: Overexpression of Fox-2 enhanced the inclusion of exon 13A and increased
      the generation of LH2(long) mRNA, whereas knockdown of Fox-2 decreased LH2(long)
      transcripts. Mutational analysis of an LH2 minigene demonstrated that 2 of the 4
      Fox binding motifs flanking LH2 exon 13A are required for inclusion of exon 13A.
      In early passage fibroblasts derived from patients with scleroderma, the
      knockdown of Fox-2 protein significantly decreased the endogenous levels of
      LH2(long) mRNA. CONCLUSION: Our findings indicate that Fox-2 plays an integral
      role in the regulation of LH2 splicing. Knockdown of Fox-2 and other methods to
      decrease the levels of fibrosis-associated LH2(long) mRNA in primary scleroderma
      cells may suggest a novel approach to strategies directed against scleroderma.

PMID- 20131249
TI  - Intravenous immunoglobulin does not prevent recurrence of congenital heart block
      in children of SSA/Ro-positive mothers.

PMID- 20131250
TI  - Increased expression of interleukin-7 in labial salivary glands of patients with
      primary Sjogren's syndrome correlates with increased inflammation.
AB  - OBJECTIVE: To study the expression levels and immunostimulatory capacities of
      interleukin-7 (IL-7) in primary Sjogren's syndrome. METHODS: Labial salivary
      gland (LSG) IL-7 expression was determined by immunohistochemistry, using a
      quantitative scoring system, in 30 patients with sicca syndrome: 15 patients with
      primary Sjogren's syndrome (SS) and 15 patients with non-SS sicca syndrome. The
      correlation of IL-7 expression in LSGs with parameters of local and peripheral
      disease was studied, and serum and salivary IL-7 levels were determined.
      Additionally, the effects of IL-7 on cytokine production by peripheral blood
      mononuclear cells (PBMCs) from patients with primary SS were determined in vitro
      by Luminex multicytokine assay and compared with the effects in control subjects.
      RESULTS: The expression of IL-7 in LSGs was higher in patients with primary SS
      compared with that in patients with non-SS sicca syndrome. IL-7 was observed
      primarily in the vicinity of lymphocytic infiltrates. Salivary IL-7 levels in
      patients with primary SS were higher than those in control subjects. In all 30
      patients with sicca syndrome, IL-7 expression in LSGs correlated with parameters
      of both local and peripheral disease. Furthermore, IL-7 stimulated T cell
      attracting and T cell-differentiating cytokines (monokine induced by interferon
      gamma [IFNgamma], IFNgamma-inducible 10-kd protein, IL-12, and IL-15), as well as
      Th1 (IFNgamma), Th2 (IL-4), Th17 (IL-17A), proinflammatory (tumor necrosis factor
      alpha and IL-1alpha), and regulatory (IL-10 and IL-13) cytokine production by
      PBMCs. All of these cytokines were previously shown to be associated with primary
      SS. The IL-7-induced increase in IL-10 production in patients with primary SS was
      reduced compared with that in control subjects. CONCLUSION: The correlation
      between LSG IL-7 expression and (local) disease parameters in primary SS as well
      as the IL-7-mediated induction of inflammatory cytokines indicate that IL-7 might
      contribute to the immunopathology of primary SS.

PMID- 20131252
TI  - Invariant natural killer T cells are natural regulators of murine
      spondylarthritis.
AB  - OBJECTIVE: To investigate the role of invariant natural killer T (iNKT) cells in
      TNF(DeltaARE/+) mice, an animal model of spondylarthritis (SpA) with both gut and
      joint inflammation. METHODS: The frequency and activation of iNKT cells were
      analyzed on mononuclear cells from the lymph nodes and livers of mice, using flow
      cytometry with alpha-galactosylceramide/CD1d tetramers and quantitative
      polymerase chain reaction for the invariant V(alpha)14-J(alpha)18 rearrangement.
      Bone marrow-derived dendritic cells (DCs) were obtained by expansion of primary
      cells with granulocyte-macrophage colony-stimulating factor followed by coculture
      with iNKT cell hybridomas, and interleukin-2 release into the cocultures was then
      measured by enzyme-linked immunosorbent assay (ELISA). Cytokine levels were
      determined by ELISA or cytometric bead array analyses of freshly isolated DCs and
      iNKT cells in mixed cocultures. TNF(DeltaARE/+) mice were backcrossed onto
      J(alpha)18(-/-) and CD1d(-/-) mice, and disease onset was evaluated by clinical
      scoring, positron emission tomography, and histology. CD1d levels were analyzed
      on mononuclear cells in paired blood and synovial fluid samples from patients
      with SpA compared with healthy control subjects. RESULTS: In the absence of iNKT
      cells, symptoms of gut and joint inflammation in TNF(DeltaARE/+)mice were
      aggravated. Invariant NKT cells were activated during the course of the disease.
      This was linked to an enrichment of inflammatory DCs, characterized by high
      levels of CD1d, particularly at draining sites of inflammation. A similar
      increase in CD1d levels was observed on DCs from patients with SpA. Inflammatory
      DCs from TNF(DeltaARE/+) mice stimulated iNKT cells to produce immunomodulatory
      cytokines, in the absence of exogenous stimulation. Prolonged, continuous
      exposure, but not short-term exposure, to tumor necrosis factor (TNF) was found
      to be responsible for the enhanced DC-NKT cell crosstalk. CONCLUSION: This mode
      of iNKT cell activation represents a natural counterregulatory mechanism for the
      dampening of TNF-driven inflammation.

PMID- 20131253
TI  - Interleukin-1 gene cluster variants with innate cytokine production profiles and
      osteoarthritis in subjects from the Genetics, Osteoarthritis and Progression
      Study.
AB  - OBJECTIVE: To assess whether genetic variation in the interleukin-1 (IL-1) gene
      cluster contributes to familial osteoarthritis (OA) by influencing innate ex vivo
      production of IL-1beta or IL-1 receptor antagonist (IL-1Ra). METHODS: Innate ex
      vivo IL-1beta and IL-1Ra production upon lipopolysaccharide (LPS) stimulation of
      whole blood cells was measured in subjects from the Genetics, Osteoarthritis and
      Progression (GARP) Study, which includes sibling pairs in which at least one
      sibling has symptomatic OA at multiple sites. Radiographic OA (ROA) was assessed
      by Kellgren/Lawrence score. Subjects from the GARP Study and controls from the
      Rotterdam Study were genotyped for 7 single-nucleotide polymorphisms (SNPs)
      encompassing the IL-1 gene cluster on chromosome 2q13. Linkage disequilibrium
      analysis and genotype and haplotype association analysis were performed to assess
      the relationship between the IL-1 gene cluster SNPs, innate ex vivo cytokine
      production, and OA. RESULTS: Among subjects in the GARP Study, the haplotype
      variable-number tandem repeat in intron 2/T+8006C/T+11100C 2/2/1 of the IL1RN
      gene was significantly associated with reduced innate ex vivo bioavailability of
      IL-1beta upon LPS stimulation (P = 0.026) and with ROA at the highest number of
      joint locations. CONCLUSION: These results show that genetic variation at the IL
      1 gene cluster is associated with lower IL-1beta bioavailability and with OA at a
      large number of joint locations. The data further indicate that, among subjects
      with OA affecting the highest number of joints, the innate immune system may be
      activated, thereby obscuring possible underlying mechanisms.

PMID- 20131254
TI  - Functional consequences of a germline mutation in the leucine-rich repeat domain
      of NLRP3 identified in an atypical autoinflammatory disorder.
AB  - OBJECTIVE: To gain insight into the pathophysiology of an atypical familial form
      of an autoinflammatory disorder, characterized by autosomal-dominant
      sensorineural hearing loss, systemic inflammation, increased secretion of
      interleukin-1beta (IL-1beta), and the absence of any cutaneous manifestations,
      and to assess the functional consequences of a missense mutation identified in
      the leucine-rich repeat (LRR) domain of NLRP3. METHODS: Microsatellite markers
      were used to test the familial segregation of the NLRP3 locus with the disease
      phenotype. All NLRP3 exons were screened for mutations by sequencing. Functional
      assays were performed in HEK 293T cells to determine the effects of mutated
      (versus normal) NLRP3 proteins on NF-kappaB activation, caspase 1 signaling, and
      speck formation. RESULTS: A heterozygous NLRP3 missense mutation (p.Tyr859Cys)
      was identified in exon 6, which encodes the LRR domain of the protein. This
      mutation was found to segregate with the disease phenotype within the family, and
      had a moderate activating effect on speck formation and procaspase 1 processing
      and did not alter the inhibitory properties of NLRP3 on NF-kappaB signaling.
      CONCLUSION: This report is the first to describe a familial form of a
      cryopyrinopathy associated with a mutation outside of exon 3 of NLRP3. This
      finding, together with the known efficacy of anti-IL-1 treatments in these
      disorders, underlines the importance of screening all exons of NLRP3 in patients
      who present with atypical manifestations. In addition, the gain of function
      associated with this mutation in terms of activation of caspase 1 signaling was
      consistent with the observed inflammatory phenotype. Therefore, this study of the
      functional consequences of an LRR mutation sheds new light on the clinical
      relevance of in vitro assays.

PMID- 20131255
TI  - High versus low dosing of oral colchicine for early acute gout flare: Twenty-four
      hour outcome of the first multicenter, randomized, double-blind, placebo
      controlled, parallel-group, dose-comparison colchicine study.
AB  - OBJECTIVE: Despite widespread use of colchicine, the evidence basis for oral
      colchicine therapy and dosing in acute gout remains limited. The aim of this
      trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose
      colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens
      producing comparable maximum plasma concentrations in healthy volunteers.
      METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel
      group study compared self-administered low-dose colchicine (1.8 mg total over 1
      hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The
      primary end point was > or = 50% pain reduction at 24 hours without rescue
      medication. RESULTS: There were 184 patients in the intent-to-treat analysis.
      Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52
      patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the
      placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue
      medication was taken within the first 24 hours by 23 patients (31.1%) in the low
      dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group
      (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low
      dose group had an adverse event (AE) profile similar to that of the placebo
      group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7-3.2).
      High-dose colchicine was associated with significantly more diarrhea, vomiting,
      and other AEs compared with low-dose colchicine or placebo. With high-dose
      colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9-56.9]), 10
      (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose
      colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8-4.8]), none
      had severe diarrhea, and none had vomiting. CONCLUSION: Low-dose colchicine
      yielded both maximum plasma concentration and early gout flare efficacy
      comparable with that of high-dose colchicine, with a safety profile
      indistinguishable from that of placebo.

PMID- 20131256
TI  - Estradiol inhibits chondrogenic differentiation of mesenchymal stem cells via
      nonclassic signaling.
AB  - OBJECTIVE: We undertook this study to examine the effects of estradiol on
      chondrogenesis of human bone marrow-derived mesenchymal stem cells (MSCs), with
      consideration of sex-dependent differences in cartilage repair. METHODS: Bone
      marrow was obtained from the iliac crest of young men. Density-gradient
      centrifugation-separated human MSCs proliferated as a monolayer in serum
      containing medium. After confluence was achieved, aggregates were created and
      cultured in a serum-free differentiation medium. We added different
      concentrations of 17beta-estradiol (E2) with or without the specific estrogen
      receptor inhibitor ICI 182.780, membrane-impermeable E2-bovine serum albumin (E2
      BSA), ICI 182.780 alone, G-1 (an agonist of G protein-coupled receptor 30 [GPR
      30]), and G15 (a GPR-30 antagonist). After 21 days, the aggregates were analyzed
      histologically and immunohistochemically; we quantified synthesized type II
      collagen, DNA content, sulfated glycosaminoglycan (sGAG) concentrations, and type
      X collagen and matrix metalloproteinase 13 (MMP-13) expression. RESULTS: The
      existence of intracellular and membrane-associated E2 receptors was shown at
      various stages of chondrogenesis. Smaller aggregates and significantly lower type
      II collagen and sGAG content were detected after treatment with E2 and E2-BSA in
      a dose-dependent manner. Furthermore, E2 enhanced type X collagen and MMP-13
      expression. Compared with estradiol alone, the coincubation of ICI 182.780 with
      estradiol enhanced suppression of chondrogenesis. Treatment with specific GPR-30
      agonists alone (G-1 and ICI 182.780) resulted in a considerable inhibition of
      chondrogenesis. In addition, we found an enhancement of hypertrophy by G-1.
      Furthermore, the specific GPR-30 antagonist G15 reversed the GPR-30-mediated
      inhibition of chondrogenesis and up-regulation of hypertrophic gene expression.
      CONCLUSION: The experiments revealed a suppression of chondrogenesis by estradiol
      via membrane receptors (GPR-30). The study opens new perspectives for influencing
      chondrogenesis on the basis of classic and nonclassic estradiol signaling.

PMID- 20131257
TI  - MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human
      osteoarthritis chondrocytes.
AB  - OBJECTIVE: Aberrant posttranscriptional regulation of matrix metalloproteinases
      (MMPs) by microRNA has emerged as an important factor in human diseases. The aim
      of this study was to determine whether the expression of MMP-13 in human
      osteoarthritis (OA) chondrocytes is regulated by microRNA. METHODS: Chondrocytes
      were stimulated with interleukin-1beta (IL-1beta) in vitro. Total RNA was
      prepared using TRIzol reagent. Polymerase chain reaction (PCR)-based arrays were
      used to determine the expression profile of 352 human microRNA. Gene expression
      was quantified using TaqMan assays, and microRNA targets were identified using
      bioinformatics. Transfection with reporter construct and microRNA mimic was used
      to verify suppression of target messenger RNA (mRNA). Gene expression of
      argonaute and Dicer was determined by reverse transcription-PCR, and expression
      of protein was determined by immunoblotting. The role of activated MAP kinases
      (MAPKs) and NF-kappaB was evaluated using specific inhibitors. RESULTS: In IL
      1beta-stimulated OA chondrocytes, 42 microRNA were down-regulated, 2 microRNA
      were up-regulated, and the expression of 308 microRNA remained unchanged. In
      silico analysis identified a sequence in the 3'-untranslated region (3'-UTR) of
      MMP-13 mRNA complementary to the seed sequence of microRNA-27b (miR-27b).
      Increased expression of MMP-13 correlated with down-regulation of miR-27b.
      Overexpression of miR-27b suppressed the activity of a reporter construct
      containing the 3'-UTR of human MMP-13 mRNA and inhibited the IL-1beta-induced
      expression of MMP-13 protein in chondrocytes. NF-kappaB and MAPK activation down
      regulated the expression of miR-27b. CONCLUSION: Our data demonstrated the
      expression of miR-27b in both normal and OA chondrocytes. Furthermore, IL-1beta
      induced activation of signal transduction pathways associated with the expression
      of MMP-13 down-regulated the expression of miR-27b. Thus, miR-27b may play a role
      in regulating the expression of MMP-13 in human chondrocytes.

PMID- 20131258
TI  - Endogenous estrogen regulation of inflammatory arthritis and cytokine expression
      in male mice, predominantly via estrogen receptor alpha.
AB  - OBJECTIVE: A number of experimental observations have associated elevated
      estrogen levels with amelioration of inflammation. The involvement of estrogen
      and estrogen receptor (ER) isotypes in the regulation of inflammation in males is
      not well understood. In this study, we used specific ERalpha and ERbeta agonists
      in male mice deficient in estrogen because of a deletion of aromatase (aromatase
      knockout [ArKO] mice) to investigate ER isotype utilization in estrogen
      regulation of inflammation. METHODS: Lipopolysaccharide (LPS)-induced cytokine
      expression and antigen-induced arthritis (AIA) were investigated in male ArKO and
      WT littermate mice, as well as in response to selective agonists of ERalpha
      (16alpha-LE2) and ERbeta (8beta-VE2). The therapeutic effect of selective ER
      agonists was also examined in mice with collagen-induced arthritis (CIA).
      RESULTS: Estrogen deficiency in ArKO mice was associated with significant
      increases in LPS-induced serum interleukin-6 (IL-6), tumor necrosis factor,
      monocyte chemotactic protein 1, and interferon-gamma levels, which were
      significantly abrogated by administration of 16alpha-LE2, but not 8beta-VE2. In
      contrast, both 16alpha-LE2 and 8beta-VE2 significantly increased LPS-induced IL
      10 levels. Estrogen deficiency was also associated with significant exacerbation
      of AIA and antigen-specific T cell proliferation, which was reversed by
      administration of either 16alpha-LE2 or 8beta-VE2. ArKO mice showed increased
      antigen-specific T cell proliferation in response to immunization with type II
      collagen (CII). Administration of 16alpha-LE2, but not 8beta-VE2, significantly
      reduced the severity of CIA, which was associated with inhibition of anti-CII
      specific IgG. CONCLUSION: These data indicate that endogenous estrogen plays an
      essential inhibitory role in inflammation in male mice and that ERalpha is the
      dominant receptor that mediates these effects.

PMID- 20131259
TI  - Mast cell-derived tryptase inhibits apoptosis of human rheumatoid synovial
      fibroblasts via rho-mediated signaling.
AB  - OBJECTIVE: An abundance of mast cells are found in the synovium of patients with
      rheumatoid arthritis (RA). However, the role of mast cells in the pathogenesis of
      RA remains unclear. This study was undertaken to elucidate a role for mast cells
      in RA by investigating the antiapoptotic effects of tryptase, a major product of
      mast cells, on RA synovial fibroblasts (RASFs). METHODS: RA synovial tissue was
      obtained from RA patients during joint replacement surgery, and histologic
      changes in the tissue were examined. The expression of cell surface molecules and
      apoptotic markers on RASFs were detected by flow cytometry. Rho activation was
      determined using a pull-down assay. RESULTS: Mast cells, bearing both c-Kit and
      tryptase, accumulated in the sublining area of proliferating synovial tissue from
      RA patients. Protease-activated receptor 2 (PAR-2), a receptor for tryptase, was
      expressed on RASFs in the lining area, close to tryptase-positive mast cells in
      the RA synovium. Fas-mediated apoptosis of RASFs was significantly inhibited, in
      a dose-dependent manner, by the addition of tryptase, and this effect correlated
      with increased activation of Rho kinase. Furthermore, Y27632, a Rho kinase
      inhibitor, reduced the antiapoptotic effect of tryptase on RASFs, suggesting that
      Rho was responsible for the antiapoptotic effects of tryptase. CONCLUSION: These
      results demonstrate that tryptase has a strong antiapoptotic effect on RASFs
      through the activation of Rho. Thus, we propose that the release of tryptase by
      mast cells leads to the binding of tryptase to PAR-2 on RASFs and inhibits the
      apoptosis of RASFs via the activation of Rho. Such mechanisms could play a
      pivotal role in the marked proliferation of RASFs and hyperplasia of synovial
      tissue seen in RA synovium.

PMID- 20131260
TI  - Association of the KIR3DS1*013 and KIR3DL1*004 alleles with susceptibility to
      ankylosing spondylitis.
AB  - OBJECTIVE: The killer cell immunoglobulin-like receptors (KIRs) form a group of
      regulatory molecules that specifically recognize HLA class I molecules. The aim
      of this study was to analyze the possible contribution of the KIR3DL1 and KIR3DS1
      alleles, in addition to HLA-B27, in the susceptibility to ankylosing spondylitis
      (AS) in a population of individuals from Spain. METHODS: We genotyped the KIR3DS1
      and KIR3DL1 alleles in 2 cohorts of patients with AS and healthy control
      subjects. In total, 270 patients with AS and 435 healthy, HLA-B27-positive
      matched control subjects from Spain were enrolled. The KIR3DS1 and KIR3DL1
      alleles were genotyped by sequence-specific oligonucleotide probe-polymerase
      chain reaction, and their association with AS was analyzed. All individuals were
      typed for HLA-B. RESULTS: The KIR3DS1*013 allele was solely responsible for the
      increased frequency of the activator receptor KIR3DS1 in patients with AS
      compared with healthy HLA-B27-positive control subjects (35.7% versus 22.6% [P =
      10(-6)], odds ratio 1.90, 95% confidence interval 1.50-2.40). The increased
      frequency of the KIR3DS1*013 allele in patients with AS was independent of the
      presence or absence of the HLA-Bw4I80 epitope. Moreover, the null allele
      KIR3DL1*004 was a unique inhibitory KIR3DL1 allele that showed a negative
      association with AS in the presence of HLA-Bw4I80. CONCLUSION: The increased
      frequency of the KIR3DS1*013 allele in patients with AS is clearly independent of
      the presence of the HLA-Bw4I80 epitope, whereas the presence of inhibitory
      allotypes such as KIR3DL1*004 demonstrated a negative association in patients
      with AS in the presence of HLA-Bw4I80. As a consequence, the influence of KIR
      genotypes on AS susceptibility would be mediated by a general imbalance between
      protective/inhibitory and risk/activating allotypes.

PMID- 20131261
TI  - Cutaneous manifestations of neonatal lupus and risk of subsequent congenital
      heart block.
AB  - OBJECTIVE: Cutaneous disease associated with placental transport of maternal anti
      SSA/Ro or anti-SSB/La antibodies is transient, and children often appear to be
      otherwise healthy. However, the impact of this manifestation of neonatal lupus
      (NL) on the risk of cardiac disease occurring in a future pregnancy is critical
      for family counseling and for powering preventive trials. The purpose of this
      study was to determine the recurrence rates of NL, with specific focus on cardiac
      NL following cutaneous NL in a child enrolled in the Research Registry for
      Neonatal Lupus (RRNL). METHODS: Fifty-eight families who were enrolled in the
      RRNL met the following inclusion criteria for our study: maternal anti-SSA/Ro or
      anti-SSB/La antibodies, a child with cutaneous NL, and a pregnancy subsequent to
      the child with cutaneous NL. RESULTS: The majority of the 58 mothers (78%) were
      Caucasian. Of 77 pregnancies that occurred following the birth of a child with
      cutaneous NL, the overall recurrence rate for any manifestation of NL was 49%
      (95% confidence interval [95% CI] 37-62%); 14 pregnancies (18.2%) were
      complicated by cardiac NL, 23 (29.9%) by cutaneous NL, and 1 (1.3%) by
      hematologic/hepatic NL. A subset analysis was restricted to the 39 children who
      were born after the initial child with cutaneous NL had been enrolled in the
      RRNL. The overall recurrence rate for NL was 36% (95% CI 20-52%); 5 pregnancies
      (12.8%) were complicated by cardiac NL and 9 (23.1%) by cutaneous NL. There were
      no significant differences in the following maternal risk factors for having a
      subsequent child with cardiac or cutaneous NL: age, race/ethnicity, anti-SSB/La
      status, diagnosis, use of nonfluorinated steroids, or breastfeeding. The sex of
      the subsequent fetus did not influence the development of cardiac or cutaneous
      NL. CONCLUSION: Based on data from this large cohort, the identification of
      cutaneous NL in an anti-SSA/Ro antibody-exposed infant is particularly important,
      since it predicts a 6-10-fold risk of a subsequent child developing cardiac NL.

PMID- 20131262
TI  - LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment
      of patients with rheumatoid arthritis: A phase I randomized, double-blind,
      placebo-controlled, proof-of-concept study.
AB  - OBJECTIVE: We undertook this study to evaluate safety, tolerability,
      pharmacokinetics, pharmacodynamics, and efficacy of LY2439821, a humanized anti
      interleukin-17 (anti-IL-17) monoclonal antibody, in a first in-human trial in
      rheumatoid arthritis (RA) patients taking oral disease-modifying antirheumatic
      drugs (DMARDs). METHODS: This randomized, double-blind, placebo-controlled study
      consisted of 2 parts. In part A, 20 patients received 1 intravenous (IV) dose of
      LY2439821 (0.06, 0.2, 0.6, or 2.0 mg/kg, escalating) or placebo followed by 8
      weeks of evaluation. End points included safety, tolerability, and
      pharmacokinetics. In part B, 77 patients received 1 IV dose of LY2439821 (0.2,
      0.6, or 2.0 mg/kg) or placebo every 2 weeks for a total of 5 doses, with a total
      evaluation period of 16 weeks. End points included safety, tolerability,
      pharmacokinetics/pharmacodynamics, and efficacy (Disease Activity Score in 28
      joints [DAS28] and percentages of patients meeting American College of
      Rheumatology 20%, 50%, or 70% improvement criteria [achieving an ACR20, ACR50, or
      ACR70 response]). The primary efficacy end point was the DAS28 at week 10.
      RESULTS: Baseline characteristics were similar across all groups. Changes in the
      DAS28 were significantly greater in the 0.2 mg/kg, 2.0 mg/kg, and all-LY2439821
      combined groups (-2.3, -2.4, and -2.3, respectively) than in the placebo group (
      1.7) at week 10 (P < or = 0.05), and these differences were significant as early
      as week 1. Percentages of ACR20, ACR50, and ACR70 responses as well as
      improvements in the ACR core set of measures were greater in LY2439821-treated
      patients than in placebo-treated patients at multiple time points. There was no
      apparent dose-response relationship in treatment-emergent adverse events.
      CONCLUSION: LY2439821 added to oral DMARDs improved signs and symptoms of RA,
      with no strong adverse safety signal noted. This first evaluation of LY2439821
      supports neutralization of IL-17 as a potential novel goal for the treatment of
      RA.

PMID- 20131263
TI  - Nucleotide-binding oligomerization domain 2 and Toll-like receptor 2 function
      independently in a murine model of arthritis triggered by intraarticular
      peptidoglycan.
AB  - OBJECTIVE: Blau syndrome is an autoinflammatory disease resulting from mutations
      in the NOD2 gene, wherein granulomatous arthritis, uveitis, and dermatitis
      develop. The mechanisms by which aberrant NOD2 causes joint inflammation are
      poorly understood. Indeed, very few studies have addressed the function of
      nucleotide-binding oligomerization domain 2 (NOD-2) in the joint. This study was
      undertaken to investigate NOD-2 function in an experimental model of arthritis
      and to explore the potential interplay between Toll-like receptor 2 (TLR-2) and
      NOD-2 in joint inflammation. METHODS: Mice deficient in TLR-2, myeloid
      differentiation factor 88 (MyD88), or NOD-2 and their wild-type controls were
      given an intraarticular injection of muramyl dipeptide (MDP), peptidoglycan (PG;
      a metabolite of which is MDP), or palmitoyl-3-cysteine-serine-lysine-4
      (Pam(3)CSK(4)), a synthetic TLR-2 agonist. Joint inflammation was assessed by
      near-infrared fluorescence imaging and histologic analysis. RESULTS: Locally
      administered PG resulted in joint inflammation, which was markedly reduced in
      mice deficient in either TLR-2 or the TLR signaling mediator MyD88. In addition
      to TLR-2 signaling events, NOD-2 mediated joint inflammation, as evidenced by the
      fact that mice deficient in NOD-2 showed significantly reduced PG-induced
      arthritis. TLR-2 or MyD88 deficiency did not influence arthritis induced by the
      specific NOD-2 agonist MDP. In addition, NOD-2 deficiency did not alter the TLR-2
      dependent joint inflammation elicited by the synthetic TLR-2 agonist
      Pam(3)CSK(4). CONCLUSION: Whereas NOD-2 and TLR-2 are both critical for the
      development of PG-induced arthritis, they appear to elicit inflammation
      independently of each other. Our findings indicate that NOD-2 plays an
      inflammatory role in arthritis.

PMID- 20131264
TI  - Interleukin-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is
      required for elevation of interleukin-22, but not interleukin-21, in autoimmune
      experimental arthritis.
AB  - OBJECTIVE: To examine the role of interleukin-23 (IL-23) in subgroup polarization
      of IL-17A-positive and/or interferon-gamma (IFNgamma)-positive T cells in
      autoimmune disease-prone DBA/1 mice with and without collagen-induced arthritis.
      METHODS: A magnetic-activated cell sorting system was used to isolate CD4+ T
      cells from the spleen of naive and type II collagen (CII)-immunized DBA/1 mice.
      These CD4+ T cells were stimulated in vitro under Th0, Th1, or different Th17
      culture conditions. Intracellular staining for IL-17A and IFNgamma was evaluated
      by flow cytometry. In addition, Th17 cytokines and T helper-specific
      transcription factors were analyzed by enzyme-linked immunosorbent assay and/or
      quantitative polymerase chain reaction. RESULTS: In CD4+ T cells from naive DBA/1
      mice, IL-23 alone hardly induced retinoic acid-related orphan receptor gammat
      (RORgammat), Th17 polarization, and Th17 cytokines, but it inhibited T-bet
      expression. In contrast, transforming growth factor beta1 (TGFbeta1)/IL-6 was a
      potent inducer of RORgammat, RORalpha, IL-17A, IL-17F, IL-21, and FoxP3 in these
      cells. In contrast to TGFbeta1/IL-6, IL-23 was critical for the induction of IL
      22 in CD4+ T cells from both naive and CII-immunized DBA/1 mice. Consistent with
      these findings, IL-23 showed a more pronounced induction of the IL-17A+IFNgamma-
      subset in CD4+ T cells from CII-immunized mice. However, in CD4+ T cells from
      naive mice, IL-23 significantly increased the TGFbeta1/IL-6-induced Th17
      polarization, including elevated levels of IL-17A and IL-17F and decreased
      expression of T-bet and FoxP3. Of note, the IL-23-induced increase in IL-17A and
      IL-17F levels was prevented in T-bet-deficient mice. CONCLUSION: IL-23 promotes
      Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation
      of IL-22, but not IL-21, levels in autoimmune arthritis. These data indicate
      different mechanisms for IL-23 and TGFbeta1/IL-6 at the transcription factor
      level during Th17 differentiation in autoimmune experimental arthritis.

PMID- 20131265
TI  - Autoantibodies against aquaporin-4 in patients with neuropsychiatric systemic
      lupus erythematosus and primary Sjogren's syndrome.

PMID- 20131266
TI  - Epidemiology of gout in women: Fifty-two-year followup of a prospective cohort.
AB  - OBJECTIVE: Despite the recent doubling of the incidence of gout among women and
      its substantial prevalence particularly in the aging female population, the risk
      factors for gout among women remain unknown. We undertook this study to evaluate
      purported risk factors for incident gout among women and to compare them with
      those among men. METHODS: Using prospective data from the Framingham Heart Study,
      we examined over a 52-year period (1950-2002) the relationship between purported
      risk factors and the incidence of gout in 2,476 women and 1,951 men. RESULTS: We
      documented 304 incident cases of gout, 104 of them among women. The incidence
      rates of gout for women per 1,000 person-years according to serum uric acid
      levels of <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9, and > or = 8.0 mg/dl were 0.8, 2.5,
      4.2, 13.1, and 27.3, respectively (P for trend < 0.0001). The magnitude of this
      association was lower than that among men (P for interaction = 0.0002).
      Multivariate relative risks conferred by increasing age (per 5 years), obesity
      (body mass index > or = 30 kg/m(2)), alcohol intake (> or = 7 ounces of pure
      alcohol/week), hypertension, and diuretic use were 1.24, 2.74, 3.10, 1.82, and
      2.39, respectively (all P < 0.05), for women. CONCLUSION: These prospective data
      with long-term followup provide evidence that higher levels of serum uric acid
      increase the risk of gout in a graded manner among women, but the rate of
      increase is lower than that among men. Increasing age, obesity, alcohol
      consumption, hypertension, and diuretic use were associated with the risk of
      incident gout among women.

PMID- 20131267
TI  - Clinical Images: Visualization of overcompensated rebound temperature against ice
      water cold challenge.

PMID- 20131268
TI  - Treatment of polyarteritis nodosa and microscopic polyangiitis without poor
      prognosis factors: A prospective randomized study of one hundred twenty-four
      patients.
AB  - OBJECTIVE: To assess the efficacy of systemic corticosteroids alone as first-line
      treatment of polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA)
      without poor-prognosis factors as defined by the Five-Factors Score (FFS), and to
      compare the efficacy and safety of azathioprine versus pulse cyclophosphamide as
      adjunctive immunosuppressive therapy for patients experiencing treatment failure
      or relapse. METHODS: This prospective, multicenter, therapeutic trial included
      124 patients with newly diagnosed PAN or MPA (FFS of 0) treated with
      corticosteroids alone. At the time of treatment failure or disease relapse,
      patients were randomized to receive 6 months of therapy with oral azathioprine or
      6 pulses of cyclophosphamide. Analyses was performed according to an intent-to
      treat strategy. RESULTS: The mean +/- SD followup period was 62 +/- 33 months.
      Treatment with corticosteroids alone induced remission in 98 patients; 50 (40%)
      of these patients had sustained disease remission, 46 (37%) experienced a
      relapse, and 2 became corticosteroid dependent (daily prednisone dose > or = 20
      mg). In 26 patients (21%), treatment with corticosteroids alone failed, and 49
      patients (40%) required additional immunosuppression. Among the 39 patients
      randomized, 13 of 19 achieved remission with cyclophosphamide pulses, and 14 of
      20 achieved remission with azathioprine. Among all patients, the 1-year and 5
      year survival rates were 99% and 92%, respectively. Six deaths occurred in the
      cyclophosphamide-treated group compared with 2 deaths in the azathioprine-treated
      group. Disease-free survival was significantly lower for patients with MPA than
      for those with PAN (P = 0.046). CONCLUSION: For patients with PAN or MPA with an
      FFS of 0, overall 5-year survival was good, but first-line corticosteroid
      treatment was able to achieve and maintain remission in only about half of the
      patients, and 40% of the patients required additional immunosuppressive therapy.
      Azathioprine or pulse cyclophosphamide was fairly effective for treating
      corticosteroid-resistant disease or major relapses.

PMID- 20131269
TI  - Early Kienbock disease cannot be detected by radiography: Comment on the clinical
      image by Ko et al.

PMID- 20131270
TI  - A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile
      neurologic, cutaneous, articular syndrome/neonatal-onset multisystem inflammatory
      disease: Novel evidence of the role of low-level mosaicism as the
      pathophysiologic mechanism underlying mendelian inherited diseases.
AB  - OBJECTIVE: Chronic infantile neurologic, cutaneous, articular syndrome (CINCA),
      also known as neonatal-onset multisystem inflammatory disease (NOMID), is a
      severe, early-onset autoinflammatory disease characterized by an urticaria-like
      rash, arthritis/arthropathy, variable neurologic involvement, and dysmorphic
      features, which usually respond to interleukin-1 blockade. CINCA/NOMID has been
      associated with dominant Mendelian inherited NLRP3 mutations. However,
      conventional sequencing analyses detect true disease-causing mutations in only
      approximately 55-60% of patients, which suggests the presence of genetic
      heterogeneity. We undertook the current study to assess the presence of somatic,
      nongermline NLRP3 mutations in a sporadic case of CINCA/NOMID. METHODS: Clinical
      data, laboratory results, and information on treatment outcomes were gathered
      through direct interviews. Exhaustive genetic studies, including Sanger method
      sequencing, subcloning, restriction fragment length polymorphism assay, and
      pyrosequencing, were performed. RESULTS: The patient's CINCA/NOMID was diagnosed
      based on clinical features (early onset of the disease, urticaria-like rash, knee
      arthropathy, and dysmorphic features). The patient has exhibited a successful
      response to anakinra within the last 28 months. Analysis of NLRP3 identified a
      novel heterozygous variant (p.D303H) that was detected in approximately 30-38% of
      circulating leukocytes. The absence of this variant in healthy controls and in
      the patient's parents suggested a de novo true disease-causing mutation.
      Additional analyses showed that this novel mutation was present in both leukocyte
      subpopulations and epithelial cells. CONCLUSION: Our findings identify the novel
      p.D303H NLRP3 variant in a Spanish patient with CINCA/NOMID as a new disease
      causing mutation, which was detected as a somatic, nongermline mutation in
      hematopoietic and nonhematopoietic cell lineages. Our data provide new insight
      into the role of low-level mosaicism in NLRP3 as the pathophysiologic mechanism
      underlying cryopyrin-associated periodic syndrome.

PMID- 20131271
TI  - Transcriptional profiling and biochemical analysis of mechanically induced
      cartilaginous tissues in a rat model.
AB  - OBJECTIVE: To characterize patterns of molecular expression that lead to
      cartilage formation in vivo in a postnatal setting, by profiling messenger RNA
      expression across the time course of mechanically induced chondrogenesis.
      METHODS: Retired breeder Sprague-Dawley rats underwent a noncritical-sized
      transverse femoral osteotomy. Experimental animals (n = 45) were subjected to
      bending stimulation (60 degrees cyclic motion in the sagittal plane for 15
      minutes/day) of the osteotomy gap beginning on day 10 after the operation.
      Control animals (n = 32) experienced continuous rigid fixation. Messenger RNA
      isolated on days 10, 17, 24, and 38 after surgery was analyzed using a microarray
      containing 608 genes involved in skeletal development, tissue differentiation,
      fracture healing, and mechanotransduction. The glycosaminoglycan (GAG) content in
      the stimulated tissues was compared with that in native articular cartilage as a
      means of assessing the progression of chondrogenic development of the tissues.
      RESULTS: The majority of the 100 genes that were differentially expressed were up
      regulated in response to mechanical stimulation. Many of these genes are
      associated with articular cartilage development and maintenance, diarthrodial
      joint development, cell adhesion, extracellular matrix synthesis, signal
      transduction, and skeletal development. Quantitative real-time polymerase chain
      reaction results were consistent with the microarray findings. The GAG content of
      the stimulated tissues increased over time and was no different from that of
      articular cartilage on day 38 after surgery. CONCLUSION: Our findings indicate
      that mechanical stimulation causes up-regulation of genes that are principally
      involved in joint cavity morphogenesis and critical to articular cartilage
      function. Further study of this type of stimulation may identify key signaling
      events required for postnatal hyaline cartilage formation.

PMID- 20131272
TI  - A novel heat-shock protein coinducer boosts stress protein Hsp70 to activate T
      cell regulation of inflammation in autoimmune arthritis.
AB  - OBJECTIVE: Stress proteins, such as members of the heat-shock protein (HSP)
      family, are up-regulated by cells in inflamed tissue and can be viewed
      functionally as "biomarkers" for the immune system to monitor inflammation.
      Exogenous administration of stress proteins has induced immunoregulation in
      various models of inflammation and has also been shown to be effective in
      clinical trials in humans. This study was undertaken to test the hypothesis that
      boosting of endogenous HSP expression can restore effective immunoregulation
      through T cells specific for stress proteins. METHODS: Stress protein expression
      was manipulated in vivo and in vitro with a food component (carvacrol), and
      immune recognition of stress proteins was studied. RESULTS: Carvacrol, a major
      compound in the oil of many Origanum species, had a notable capacity to coinduce
      cellular Hsp70 expression in vitro and, upon intragastric administration, in
      Peyer's patches of mice in vivo. As a consequence, carvacrol specifically
      promoted T cell recognition of endogenous Hsp70, as demonstrated in vitro by the
      activation of an Hsp70-specific T cell hybridoma and in vivo by amplified T cell
      responses to Hsp70. Carvacrol administration also increased the number of
      CD4+CD25+FoxP3+ T cells, systemically in the spleen and locally in the joint, and
      almost completely suppressed proteoglycan-induced experimental arthritis.
      Furthermore, protection against arthritis could be transferred with T cells
      isolated from carvacrol-fed mice. CONCLUSION: These findings illustrate that a
      food component can boost protective T cell responses to a self stress protein and
      down-regulate inflammatory disease, i.e., that the immune system can respond to
      diet.

PMID- 20131273
TI  - IRF5 is associated with primary antiphospholipid syndrome, but is not a major
      risk factor.

PMID- 20131274
TI  - Human single-chain variable fragment that specifically targets arthritic
      cartilage.
AB  - OBJECTIVE: To demonstrate that posttranslational modification of type II collagen
      (CII) by reactive oxygen species (ROS), which are known to be present in inflamed
      arthritic joints, can give rise to epitopes specific to damaged cartilage in
      rheumatoid arthritis (RA) and osteoarthritis (OA) and to establish a proof of
      concept that antibodies specific to ROS-modified CII can be used to target
      therapeutics specifically to inflamed arthritic joints. METHODS: We used a
      semisynthetic phage display human antibody library to raise single-chain variable
      fragments (scFv) specific to ROS-modified CII. The specificity of anti-ROS
      modified CII scFv to damaged arthritic cartilage was assessed in vitro by
      immunostaining articular cartilage from RA and OA patients and from normal
      controls. The in vivo targeting potential was tested using mice with antigen
      induced arthritis, in which localization of anti-ROS-modified CII scFv in the
      joints was determined. The therapeutic effect of anti-ROS-modified CII scFv fused
      to soluble murine tumor necrosis factor receptor II-Fc fusion protein (mTNFRII
      Fc) was also investigated. RESULTS: The anti-ROS-modified CII scFv bound to
      damaged arthritic cartilage from patients with RA and OA but not to normal
      preserved cartilage. When systemically administered to arthritic mice, the anti
      ROS-modified CII accumulated selectively at the inflamed joints. Importantly,
      when fused to mTNFRII-Fc, it significantly reduced inflammation in arthritic
      mice, as compared with the effects of mTNFRII-Fc alone or of mTNFRII-Fc fused to
      an irrelevant scFv. CONCLUSION: Our findings indicate that biologic therapeutics
      can be targeted specifically to arthritic joints and suggest a new approach for
      the development of novel treatments of arthritis.

PMID- 20131275
TI  - Deletion of either CD55 or CD97 ameliorates arthritis in mouse models.
AB  - OBJECTIVE: CD55 (decay-accelerating factor) is best known for its role in the
      negative regulation of the complement system. Indeed, lack of this molecule leads
      to disease aggravation in many autoimmune disease models. However, CD55 is
      abundantly present on fibroblast-like synoviocytes and is also a ligand of the
      adhesion-class heptahelical receptor CD97, which is expressed by infiltrating
      macrophages. Treatment with antibodies to CD97 ameliorates the collagen-induced
      model of rheumatoid arthritis (RA) in DBA/1 mice, but the net contribution of
      CD55 is unknown. This study was undertaken to investigate the role of CD55 in
      experimental RA. METHODS: Arthritis was induced in wild-type, CD55(-/-), and
      CD97(-/-) mice using collagen-induced and K/BxN serum-transfer models. Incidence
      of arthritis was monitored over time, and disease activity was assessed by
      clinical and immunohistochemical evaluation. RESULTS: In contrast to observations
      in many inflammatory disease models, lack of CD55 resulted in decreased arthritis
      in experimental models of RA. Consistent with the previously reported effects of
      anti-CD97 antibody treatment, CD97(-/-) mice had reduced arthritis activity
      compared with wild-type controls. CONCLUSION: Our findings indicate that the lack
      of CD55 or CD97 in 2 different models of arthritis increases resistance to the
      disease. These findings provide insight into a role for CD55 interaction with
      CD97 in the pathogenesis of RA and suggest that therapeutic strategies that
      disrupt CD55/CD97 may be clinically beneficial.

PMID- 20131276
TI  - Golimumab, a new human anti-tumor necrosis factor alpha antibody, administered
      intravenously in patients with active rheumatoid arthritis: Forty-eight-week
      efficacy and safety results of a phase III randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: To assess the efficacy and safety of intravenous administration of
      golimumab in patients with rheumatoid arthritis (RA). METHODS: Adult patients
      with RA in whom disease activity was persistent despite treatment with
      methotrexate (MTX) at a dosage of 15-25 mg/week for > or = 4 weeks were
      randomized to receive intravenous infusions of placebo plus MTX or intravenous
      infusions of golimumab at a dose of 2 mg/kg or 4 mg/kg, with or without MTX,
      every 12 weeks through week 48. Patients with <20% improvement in the swollen and
      tender joint counts could enter early escape and receive additional active
      treatment (week 16) or could have their dose regimen adjusted (week 24). The
      primary end point was the proportion of patients achieving a 50% response
      according to the American College of Rheumatology improvement criteria (ACR50) at
      week 14. RESULTS: The primary study end point was not met (at week 14, an ACR50
      response was observed in 21% of the patients treated with golimumab plus MTX
      compared with 13% of the patients treated with placebo plus MTX [P = 0.051]). By
      week 24, significantly more patients treated with golimumab plus MTX had achieved
      an ACR50 response. Differences in the proportion of patients achieving an ACR50
      response between the group receiving golimumab monotherapy and the group
      receiving placebo plus MTX were not significant at either week 14 (16% versus
      13%) or week 24 (10% versus 9%). At week 48, the proportions of patients
      achieving ACR20 and ACR50 responses were highest among those who had received
      golimumab 4 mg/kg plus MTX (70% and 48%, respectively). Concomitant treatment
      with MTX was associated with a lower incidence of antibodies to golimumab. The
      most commonly reported adverse events through week 48 were infections (48% of
      patients treated with golimumab with or without MTX and 41% of patients receiving
      placebo plus MTX). CONCLUSION: The primary end point was not met. However,
      intravenously administered golimumab plus MTX appears to have benefit in the
      longer-term reduction of RA signs/symptoms in MTX-resistant patients, with no
      unexpected safety concerns.

PMID- 20131277
TI  - Left ventricular structure and function in patients with rheumatoid arthritis, as
      assessed by cardiac magnetic resonance imaging.
AB  - OBJECTIVE: Heart failure is a major contributor to cardiovascular morbidity and
      mortality in patients with rheumatoid arthritis (RA), but little is known about
      myocardial structure and function in this population. This study was undertaken
      to assess the factors associated with progression to heart failure in patients
      with RA. METHODS: With the use of cardiac magnetic resonance imaging, measures of
      myocardial structure and function were assessed in men and women with RA enrolled
      in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events
      in Rheumatoid Arthritis study, a cohort study of subclinical cardiovascular
      disease in patients with RA, in comparison with non-RA control subjects from a
      cohort enrolled in the Baltimore Multi-Ethnic Study of Atherosclerosis. RESULTS:
      Measures of myocardial structure and function were compared between 75 patients
      with RA and 225 frequency-matched controls. After adjustment for confounders, the
      mean left ventricular mass was found to be 26 gm lower in patients with RA
      compared with controls (P < 0.001), an 18% difference. In addition, the mean left
      ventricular ejection fraction, cardiac output, and stroke volume were modestly
      lower in the RA group compared with controls. The mean left ventricular end
      systolic and end diastolic volumes did not differ between the groups. In patients
      with RA, higher levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies
      and current use of biologic agents, but not other measures of disease activity or
      severity, were associated with significantly lower adjusted mean values for the
      left ventricular mass, end diastolic volume, and stroke volume, but not with
      ejection fraction. The combined associations of anti-CCP antibody level and
      biologic agent use with myocardial measures were additive, without evidence of
      interaction. CONCLUSION: These findings suggest that the progression to heart
      failure in RA may occur through reduced myocardial mass rather than hypertrophy.
      Both modifiable and nonmodifiable factors may contribute to lower levels of left
      ventricular mass and volume.

PMID- 20131278
TI  - Failure of intravenous immunoglobulin to prevent congenital heart block: Findings
      of a multicenter, prospective, observational study.
AB  - OBJECTIVE: Congenital heart block (CHB) is presumed to be caused by
      transplacental passage of maternal immunoglobulin against Ro and La
      ribonucleoproteins. The recurrence rate in subsequent pregnancies following the
      birth of a child with CHB is approximately 19%. The purpose of this study was to
      determine whether intravenous immunoglobulin (IVIG) therapy could prevent the
      development of CHB in the fetuses of high-risk pregnant women. METHODS: A total
      of 24 pregnancies in 22 women who had a previous pregnancy in which CHB
      developed, were over the age of 18 years, were <12 weeks pregnant, and had anti
      Ro, anti-La, or both antibodies were monitored in this multicenter, prospective,
      observational study. Fifteen patients received infusions of IVIG. The 9
      pregnancies in the remaining 7 patients served as controls. IVIG was administered
      at a dose of 400 mg/kg at weeks 12, 15, 18, 21, and 24 of pregnancy.
      Echocardiograms were performed at least every 3 weeks from week 15 to week 30 of
      gestation. Electrocardiograms were obtained at birth. The outcome measure was the
      development of third-degree CHB detected by fetal echocardiogram. RESULTS: CHB
      developed in 3 babies among the 15 pregnancies in the treatment group (20%) and
      in 1 baby among the 9 pregnancies in the control group (11%). CHB was detected at
      weeks 18, 23, and 26, respectively, in the 3 babies in the treated group and at
      week 19 in the baby in the control group. Three of the affected pregnancies ended
      in termination; 2 for reasons related to the fetal disease and 1 for reasons
      related to both maternal (severe pulmonary hypertension) and fetal disease (at 21
      weeks of gestation). CONCLUSION: IVIG at the dose and frequency used in this
      study was not effective as prophylactic therapy for CHB in high-risk mothers.

PMID- 20131279
TI  - Premature arthritis is a distinct type II collagen phenotype.
AB  - Mutations in the gene encoding type II collagen (COL2A1) give rise to a spectrum
      of phenotypes predominantly affecting cartilage and bone. These chondrodysplasias
      are typically characterized by disproportionately short stature, eye
      abnormalities, cleft palate, and hearing loss. It is less recognized that
      mutations in COL2A1 can also present as degenerative joint disease in the absence
      of any other phenotypic clues. We report 2 Australian families presenting with an
      isolated arthritis phenotype, segregating as a dominant trait affecting both
      large and small joints, prior to age 30 years. Sequencing of COL2A1 in the
      propositi revealed 2 sequence changes resulting in glycine substitutions in the
      triple-helical domain of type II collagen. We review the increasing evidence
      implicating COL2A1 mutations in individuals presenting with isolated degenerative
      joint disease, aiming to alert physicians who assess these patients to this
      possibility. The importance of finding a COL2A1 mutation in such patients lies in
      the subsequent ability to accurately assess recurrence risks, offer early
      (including prenatal) diagnosis, and provide information regarding the natural
      history of the condition. Most importantly, it enables at-risk individuals to be
      identified for implementation of preventative strategies (i.e., weight loss,
      joint-friendly exercise programs) and early ameliorative management of their
      condition.

PMID- 20131280
TI  - Tobacco: from pre-Columbian use to the appearance of rheumatoid arthritis in the
      Old World?

PMID- 20131281
TI  - Cellular characterization of the gouty tophus: a quantitative analysis.
AB  - OBJECTIVE: To characterize the cellular architecture of the tophus and to
      determine the presence of cytokines implicated in the initiation and resolution
      of gouty inflammation. METHODS: Sixteen fixed, paraffin-embedded, uninfected
      tophus samples were surgically obtained from 12 patients with microscopically
      proven gout and were analyzed by quantitative immunohistochemistry. The number of
      cells present in the corona and fibrovascular zones of the tophus was analyzed by
      Genmod mixed models analysis. RESULTS: Numerous CD68+ mononucleated and
      multinucleated cells were present within the corona zone. Mast cells were
      identified in all tophus samples and at similar densities throughout the corona
      and fibrovascular zones. In contrast, neutrophils were rarely observed. Plasma
      cells were present in very high numbers within the corona zone. The overall
      number of CD20+ B cells was much lower. However, in 6 of 12 patients (50%), at
      least 1 B cell aggregate was present in the fibrovascular zone. Large numbers of
      cells expressing interleukin-1beta (IL-1beta) were observed in the corona zone.
      Transforming growth factor beta1 (TGFbeta1)-expressing mononucleated cells were
      also identified. The number of CD68+ cells correlated with the number of cells
      expressing IL-1beta (r = 0.691, P = 0.009) and the number expressing TGFbeta1 (r
      = 0.518, P = 0.04). CONCLUSION: The tophus represents a complex and organized
      chronic inflammatory tissue response to monosodium urate monohydrate crystals
      involving both innate and adaptive immune cells. The coexpression of IL-1beta and
      TGFbeta1 suggests that both proinflammatory and antiinflammatory factors present
      within the tophus contribute to a cycle of chronic inflammation, attempted
      resolution, and tissue remodeling.

PMID- 20131282
TI  - Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and
      subchondral bone deterioration in osteoarthritic knees.
AB  - OBJECTIVE: Perturbation of Wnt signaling components reportedly regulates
      chondrocyte fate and joint disorders. The Wnt inhibitor Dkk-1 mediates remodeling
      of various tissue types. We undertook this study to examine whether control of
      Dkk-1 expression prevents joint deterioration in osteoarthritic (OA) knees.
      METHODS: Anterior cruciate ligament transection-and collagenase-induced OA in rat
      knees was treated with end-capped phosphorothioate Dkk-1 antisense
      oligonucleotide (Dkk-1-AS). Articular cartilage destruction, cartilage
      degradation markers, bone mineral density (BMD), and subchondral trabecular bone
      volume of injured knee joints were measured using Mankin scoring, enzyme-linked
      immunosorbent assay, dual x-ray absorptiometry, and histomorphometry. Dkk-1
      responsive molecule expression and apoptotic cells in knee tissue were detected
      by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting,
      and TUNEL staining. RESULTS: Up-regulated Dkk-1 expression was associated with
      increased Mankin score and with increased serum levels of cartilage oligomeric
      matrix protein and C-telopeptide of type II collagen (CTX-II) during OA
      development. Dkk-1-AS treatment alleviated OA-associated increases in Dkk-1
      expression, Mankin score, cartilage fibrillation, and serum cartilage degradation
      markers. Dkk-1-AS also alleviated epiphyseal BMD loss and subchondral bone
      exposure associated with altered serum levels of osteocalcin and CTX-I. The
      treatment abrogated chondrocyte/osteoblast apoptosis and subchondral trabecular
      bone remodeling in OA. Dkk-1 knockdown increased levels of nuclear beta-catenin
      and phosphorylated Ser(473)-Akt but attenuated expression of inflammatory factors
      (Toll-like receptor 4 [TLR-4], TLR-9, interleukin-1beta, and tumor necrosis
      factor alpha), the apoptosis regulator Bax, matrix metalloproteinase 3, and RANKL
      in OA knee joints. CONCLUSION: Interference with the cartilage- and bone
      deleterious actions of Dkk-1 provides therapeutic potential for alleviating
      cartilage destruction and subchondral bone damage in OA knee joints.

PMID- 20131283
TI  - Birth outcomes in women who have taken leflunomide during pregnancy.
AB  - OBJECTIVE: In preclinical reproductive studies, leflunomide was found to be
      embryotoxic and teratogenic. Women treated with leflunomide are advised to avoid
      pregnancy; those who become pregnant are advised to reduce fetal exposure through
      a cholestyramine drug elimination procedure. The present study was undertaken to
      investigate pregnancy outcomes in women who received leflunomide and were treated
      with cholestyramine during pregnancy. METHODS: Sixty-four pregnant women with
      rheumatoid arthritis (RA) who were treated with leflunomide during pregnancy
      (95.3% of whom received cholestyramine), 108 pregnant women with RA not treated
      with leflunomide, and 78 healthy pregnant women were enrolled in a prospective
      cohort study between 1999 and 2009. Information was collected via interview of
      the mothers, review of medical records, and specialized physical examination of
      infants. RESULTS: There were no significant differences in the overall rate of
      major structural defects in the exposed group (3 of 56 live births [5.4%])
      relative to either comparison group (each 4.2%)(P = 0.13). The rate was similar
      to the 3-4% expected in the general population. There was no specific pattern of
      major or minor anomalies. Infants in both the leflunomide-exposed and non
      leflunomide-exposed RA groups were born smaller and earlier relative to infants
      of healthy mothers; however, after adjustment for confounding factors, there were
      no significant differences between the leflunomide-exposed and non-leflunomide
      exposed RA groups. CONCLUSION: Although the sample size is small, these data do
      not support the notion that there is a substantial increased risk of adverse
      pregnancy outcomes due to leflunomide exposure among women who undergo
      cholestyramine elimination procedure early in pregnancy. These findings can
      provide some reassurance to women who inadvertently become pregnant while taking
      leflunomide and undergo the washout procedure.

PMID- 20131284
TI  - Management of nonresponse to rituximab in rheumatoid arthritis: predictors and
      outcome of re-treatment.
AB  - OBJECTIVE: A proportion of patients with rheumatoid arthritis (RA) have disease
      that fails to respond to an initial cycle of rituximab. Using highly sensitive
      flow cytometry (HSFC), it has been shown that most patients who do not exhibit a
      response, as measured using the European League Against Rheumatism (EULAR)
      criteria, have persistent circulating B cell levels at week 2 after initial
      treatment with rituximab. This study was undertaken to examine whether an
      additional cycle of rituximab would improve B cell depletion and clinical
      response in patients whose disease did not respond to the initial cycle. METHODS:
      Patients with RA (n = 158) were treated with a first cycle of rituximab (2
      infusions of 1 gm each). Clinical responses were assessed using EULAR criteria,
      and patients were categorized as either first-cycle responders or first-cycle
      nonresponders. Baseline characteristics of first-cycle nonresponders (n = 38) and
      first-cycle responders (n = 65) with complete data were compared. First-cycle
      nonresponders (n = 25) were treated with a second cycle of rituximab at least 6
      months after the first cycle. HSFC was performed at baseline, immediately prior
      to the second infusion (week 2), 1 month after the second infusion (week 6), and
      then every 3 months for each cycle of rituximab. Complete B cell depletion was
      defined as being <0.0001 x 10(9) cells/liter. RESULTS: At baseline, the number of
      preplasma cells was significantly higher in first-cycle nonresponders than in
      first-cycle responders (P = 0.003). Following the first infusion of the first
      cycle of rituximab, only 9% of first-cycle nonresponders (3 of 34) exhibited
      complete depletion of B-lineage cells, compared with 37% of first-cycle
      responders (22 of 59) (P = 0.007). Following the first infusion of the second
      cycle of rituximab, 38% of first-cycle nonresponders exhibited complete
      depletion. Twenty-six weeks after the second cycle, there was a significant
      improvement in the Disease Activity Score in 28 joints, with 72% of patients
      exhibiting a EULAR response. CONCLUSION: RA patients whose disease did not
      respond to an initial cycle of rituximab have higher circulating preplasma cell
      numbers at baseline and incomplete depletion. Our findings indicate that an
      additional cycle of rituximab administered prior to total B cell repopulation
      enhances B cell depletion and clinical responses.

PMID- 20131285
TI  - Buffy's, B cells, and membrane BAFF.

PMID- 20131286
TI  - Decreased expression of heparin-binding epidermal growth factor-like growth
      factor as a newly identified pathogenic mechanism of antiphospholipid-mediated
      defective placentation.
AB  - OBJECTIVE: Heparin-binding epidermal growth factor-like growth factor (HB-EGF)
      plays a role in blastocyst implantation and is down-regulated in preeclampsia and
      in hypertensive pregnancy disorders associated with defective extravillous
      trophoblast invasion. Defective placentation and severe preeclampsia are also
      features of the antiphospholipid syndrome (APS). The purpose of this study was to
      investigate whether abnormal HB-EGF expression plays a pathogenic role in
      antiphospholipid antibody (aPL)-mediated defective placentation. METHODS: HB-EGF
      expression in placental tissue was evaluated by Western blotting and messenger
      RNA analysis in normal and APS placentae. Polyclonal IgG fractions or monoclonal
      beta(2)-glycoprotein I-dependent aPL and their respective controls were
      investigated for the following 4 features: their binding to human trophoblast
      monolayers, as determined by cell enzyme-linked immunosorbent assay (ELISA);
      their effect on HB-EGF expression by Western blotting in trophoblast cell
      extracts as well as by ELISA as a protein secreted in the culture supernatants;
      their inhibitory effect on in vitro trophoblast invasiveness, as evaluated by
      Matrigel assay; and their inhibitory effect on matrix metalloproteinase (MMP)
      levels, as measured by gelatin zymography. Experiments were also performed in the
      presence of serial concentrations of heparin or recombinant HB-EGF. RESULTS:
      Placental APS tissue displayed reduced expression of HB-EGF. Polyclonal and
      monoclonal aPL bound to trophoblast monolayers and significantly reduced the in
      vitro synthesis and secretion of HB-EGF. Heparin inhibited aPL binding and
      restored HB-EGF expression in a dose-dependent manner. Addition of recombinant HB
      EGF reduced the in vitro aPL-induced inhibition of Matrigel invasiveness as well
      as MMP-2 levels. CONCLUSION: These preliminary findings suggest that the
      reduction of aPL-mediated HB-EGF represents an additional mechanism that is
      responsible for the defective placentation associated with APS and that heparin
      protects from aPL-induced damage by inhibiting antibody binding.

PMID- 20131287
TI  - Disruption of tight junction structure in salivary glands from Sjogren's syndrome
      patients is linked to proinflammatory cytokine exposure.
AB  - OBJECTIVE: Disorganization of acinar cell apical microvilli and the presence of
      stromal collagen in the acinar lumen suggest that the labial salivary gland (LSG)
      barrier function is impaired in patients with Sjogren's syndrome. Tight junctions
      define cell polarity and regulate the paracellular flow of ions and water,
      crucial functions of acinar cells. This study was undertaken to evaluate the
      expression and localization of tight junction proteins in LSGs from patients with
      SS and to determine in vitro the effects of tumor necrosis factor alpha
      (TNFalpha) and interferon-gamma (IFNgamma) on tight junction integrity of
      isolated acini from control subjects. METHODS: Twenty-two patients and 15
      controls were studied. The messenger RNA and protein levels of tight junction
      components (claudin-1, claudin-3, claudin-4, occludin, and ZO-1) were determined
      by semiquantitative reverse transcriptase-polymerase chain reaction and Western
      blotting. Tight junction protein localization was determined by
      immunohistochemistry. Tight junction ultrastructure was examined by transmission
      electron microscopy. Isolated acini from control subjects were treated with
      TNFalpha and IFNgamma. RESULTS: Significant differences in tight junction protein
      levels were detected in patients with SS. ZO-1 and occludin were strongly down
      regulated, while claudin-1 and claudin-4 were overexpressed. Tight junction
      proteins localized exclusively to apical domains in acini and ducts of LSGs from
      controls. In SS patients, the ZO-1 and occludin the apical domain presence of
      decreased, while claudin-3 and claudin-4 was redistributed to the basolateral
      plasma membrane. Exposure of isolated control acini to TNFalpha and IFNgamma
      reproduced these alterations in vitro. Ultrastructural analysis associated tight
      junction disorganization with the presence of endocytic vesicles containing
      electron-dense material that may represent tight junction components. CONCLUSION:
      Our findings indicate that local cytokine production in LSGs from SS patients may
      contribute to the secretory gland dysfunction observed in SS patients by altering
      tight junction integrity of epithelial cells, thereby decreasing the quality and
      quantity of saliva.

PMID- 20131288
TI  - Overexpression of the growth arrest and DNA damage-induced 45alpha gene
      contributes to autoimmunity by promoting DNA demethylation in lupus T cells.
AB  - OBJECTIVE: Demethylation of CD11a and CD70 regulatory regions in CD4+ T cells
      contributes to the development of autoreactivity and overstimulation of
      autoantibodies. Because growth arrest and DNA damage-induced 45alpha
      (GADD45alpha) reduces epigenetic silencing of genes by removing methylation
      marks, this study examined whether the gadd45A gene could contribute to
      autoimmunity by promoting DNA demethylation in T cells from patients with
      systemic lupus erythematosus (SLE). METHODS: Levels of GADD45alpha, CD11a, and
      CD70 messenger RNA (mRNA) and protein were detected by real-time reverse
      transcription-polymerase chain reaction and Western blotting or flow cytometry.
      Global DNA methylation was evaluated using Methylamp global DNA methylation
      quantification kits. Detection of CD4+ T cell proliferation and autologous B cell
      IgG antibodies was performed using commercially available kits. CD11a and CD70
      promoter methylation was determined with bisulfite sequencing. RESULTS: Elevated
      gadd45A mRNA expression and global DNA hypomethylation were observed in CD4+ T
      cells from SLE patients. The levels of gadd45A mRNA were inversely proportional
      to the levels of DNA methylation. Positive correlations were found between
      gadd45A and CD11a/CD70 mRNA levels. Expression of gadd45A mRNA was increased in
      CD4+ T cells following ultraviolet B irradiation, and this was accompanied by
      increased levels of CD11a and CD70 mRNA. Moreover, increased expression of
      gadd45A, CD11a, and CD70 mRNA was accompanied by increased autoreactivity and
      excessive B cell stimulation in gadd45A-transfected CD4+ T cells. CD11a promoter
      methylation was also significantly reduced in transfected cells. Transfection of
      gadd45A small interfering RNA inhibited the autoreactivity of SLE CD4+ T cells
      and led to significant increases in the methylation levels of the CD11a and CD70
      promoter regions. CONCLUSION: These findings indicate that gadd45A may contribute
      to lupus-like autoimmunity by promoting DNA demethylation in SLE CD4+ T cells.

PMID- 20131289
TI  - Clinical Images: Entero-Behcet's disease.

PMID- 20131291
TI  - Protection against anti-citrullinated protein antibody-positive rheumatoid
      arthritis is predominantly associated with HLA-DRB1*1301: a meta-analysis of HLA
      DRB1 associations with anti-citrullinated protein antibody-positive and anti
      citrullinated protein antibody-negative rheumatoid arthritis in four European
      populations.
AB  - OBJECTIVE: The protective effect of HLA-DRB1 alleles on the development of
      rheumatoid arthritis (RA) is poorly understood. The aim of this study was to
      perform a meta-analysis of 4 European populations to investigate which HLA-DRB1
      alleles are associated with protection in anti-citrullinated protein antibody
      (ACPA)-positive RA and ACPA-negative RA. METHODS: Data for >2,800 patients and
      >3,000 control subjects for whom information on HLA-DRB1 typing and ACPA status
      was available were collected from 4 European countries: Norway, Sweden, The
      Netherlands, and Spain. The odds ratios (ORs) and 95% confidence intervals (95%
      CIs) associated with the different HLA-DRB1 alleles were analyzed in a combined
      meta-analysis focused on protective alleles and classifications. The analysis of
      ACPA-positive RA was stratified for the shared epitope (SE) alleles, to correct
      for skewing due to this association. RESULTS: In ACPA-positive RA, the only
      alleles that conveyed protection after stratification for SE were HLA-DRB1*13
      alleles (OR 0.54 [95% CI 0.38-0.77]). The protective effect of the allele
      classifications based on the DERAA and D70 sequences was no longer present after
      exclusion of DRB1*13 (for D70, OR 0.97 [95% CI 0.75-1.25]), indicating that
      DRB1*13, rather than the DERAA or D70 sequence as such, is associated with
      protection. Among the DRB1*13 alleles, only DRB1*1301 was associated with
      protection (OR 0.24 [95% CI 0.09-0.59]). Protection appeared to follow a north-to
      south gradient, with the strongest association in northern European countries. In
      ACPA-negative RA, there were no robust associations with HLA-DRB1 alleles.
      CONCLUSION: Our data do not support any of the classifications of protective
      alleles and indicate that protection against ACPA-positive RA is predominantly
      associated with HLA-DRB1*1301.

PMID- 20131292
TI  - Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutieres
      syndrome.
AB  - OBJECTIVE: Aicardi-Goutieres syndrome (AGS) is an early-onset encephalopathy
      resembling congenital viral infection that is characterized by basal ganglia
      calcifications, loss of white matter, cerebrospinal fluid (CSF) lymphocytosis,
      and elevated interferon-alpha levels in the CSF. Studies have shown that AGS is
      an autosomal-recessive disease linked to mutations in 5 genes, encoding the 3'
      repair DNA exonuclease 1 (TREX1), the 3 subunits of ribonuclease H2 (RNASEH2A-C),
      and sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1). In
      this study we further characterized the phenotypic spectrum of this disease.
      METHODS: Clinical and laboratory data were obtained from 26 patients fulfilling
      the clinical diagnostic criteria for AGS. Genomic DNA was screened for mutations
      in all 5 AGS genes by direct sequencing, and sera were analyzed for
      autoantibodies. RESULTS: In 20 patients with AGS, 20 mutations, 12 of which were
      novel, were identified in all 5 AGS genes. Clinical and laboratory investigations
      revealed a high prevalence of features (some not previously described in patients
      with AGS) that are commonly seen in patients with systemic lupus erythematosus
      (SLE), such as thrombocytopenia, leukocytopenia, antinuclear antibodies,
      erythematous lesions, oral ulcers, and arthritis, which were observed in 12 (60%)
      of 20 patients with AGS. Moreover, the coexistence of AGS and SLE, was for the
      first time, demonstrated in 2 patients with molecularly proven AGS. CONCLUSION:
      These findings expand the phenotypic spectrum of lupus erythematosus in AGS and
      provide further insight into its disease mechanisms by showing that activation of
      the innate immune system as a result of inherited defects in nucleic acid
      metabolism could lead to systemic autoimmunity.

PMID- 20131293
TI  - Selective blockade of BAFF for the prevention and treatment of systemic lupus
      erythematosus nephritis in NZM2410 mice.
AB  - OBJECTIVE: To determine whether BAFF or combined BAFF/APRIL blockade is effective
      in a mouse model of systemic lupus erythematosus (SLE) nephritis characterized by
      rapidly progressive glomerulosclerosis. METHODS: NZM2410 mice at early and late
      stages of SLE nephritis were treated with a short course of BAFF-R-Ig or TACI-Ig
      fusion protein. Proteinuria and serologic profile were evaluated every 2 weeks.
      Immunohistochemical, flow cytometric, and enzyme-linked immunospot analyses of
      the spleen, kidney, and bone marrow were performed after 8 weeks and after 33
      weeks. RESULTS: A short course of selective blockade of BAFF alone was sufficient
      to prevent and treat SLE nephritis in NZM2410 mice, despite the formation of
      pathogenic autoantibodies. Decreases in spleen size and B cell depletion
      persisted for more than 33 weeks after treatment and resulted in secondary
      decreases in CD4 memory T cell formation and activation of splenic and peripheral
      monocytes. Immune complex deposition in the kidneys was dissociated from renal
      damage and from activation of renal endothelial and resident dendritic cells.
      CONCLUSION: Selective blockade of BAFF alone, which resulted in B cell depletion
      and splenic collapse, was sufficient to prevent and treat the disease in this
      model of noninflammatory SLE nephritis. This shows that the inflammatory
      microenvironment may be a determinant of the outcome of B cell modulation
      strategies.

PMID- 20131294
TI  - SirT1 enhances survival of human osteoarthritic chondrocytes by repressing
      protein tyrosine phosphatase 1B and activating the insulin-like growth factor
      receptor pathway.
AB  - OBJECTIVE: The protein deacetylase SirT1 inhibits apoptosis in a variety of cell
      systems by distinct mechanisms, yet its role in chondrocyte death has not been
      explored. We undertook the present study to assess the role of SirT1 in the
      survival of osteoarthritic (OA) chondrocytes in humans. METHODS: SirT1, protein
      tyrosine phosphatase 1B (PTP1B), and PTP1B mutant expression plasmids as well as
      SirT1 small interfering RNA (siRNA) and PTP1B siRNA were transfected into primary
      human chondrocytes. Levels of apoptosis were determined using flow cytometry, and
      activation of components of the insulin-like growth factor receptor (IGFR)/Akt
      pathway was assessed using immunoblotting. OA and normal knee cartilage samples
      were subjected to immunohistochemical analysis. RESULTS: Expression of SirT1 in
      chondrocytes led to increased chondrocyte survival in either the presence or the
      absence of tumor necrosis factor alpha/actinomycin D, while a reduction of SirT1
      by siRNA led to increased chondrocyte apoptosis. Expression of SirT1 in
      chondrocytes led to activation of IGFR and the downstream kinases
      phosphatidylinositol 3-kinase, phosphoinosite-dependent protein kinase 1, mTOR,
      and Akt, which in turn phosphorylated MDM2, inhibited p53, and blocked apoptosis.
      Activation of IGFR occurs at least in part via SirT1-mediated repression of
      PTP1B. Expression of PTP1B in chondrocytes increased apoptosis and reduced IGFR
      phosphorylation, while down-regulation of PTP1B by siRNA significantly decreased
      apoptosis. Examination of cartilage from normal donors and OA patients revealed
      that PTP1B levels are elevated in OA cartilage in which SirT1 levels are
      decreased. CONCLUSION: For the first time, it has been demonstrated that SirT1 is
      a mediator of human chondrocyte survival via down-regulation of PTP1B, a potent
      proapoptotic protein that is elevated in OA cartilage.

PMID- 20131295
TI  - Reactivity with dichotomous determinants of Ro 60 stratifies autoantibody
      responses in lupus and primary Sjogren's syndrome.
AB  - OBJECTIVE: Analysis of B cell determinants of Ro 60 exposed on the surface of
      apoptotic cells (apotopes) or intracellular epitopes provides insight into the
      structural forms of the autoantigen that break immune tolerance. This study was
      initiated to compare anti-Ro 60 responses in systemic lupus erythematosus (SLE)
      and primary Sjogren's syndrome (SS) against membrane-bound and intracellular
      forms of Ro 60. METHODS: The reactivity of autoantibodies from patients with SLE
      and primary SS to Ro 60 apotopes and epitopes was assessed by multiparameter flow
      cytometry and solid-phase immunoassay. Anti-Ro 60 IgG was eluted from early
      apoptotic cells or recombinant Ro 60 immobilized on nitrocellulose, and binding
      to membrane-bound and intracellular forms of Ro 60 was quantitated by flow
      cytometry. RESULTS: An immunodominant apotope, which was recognized by IgG from a
      subset of SLE patients with anti-Ro, but not anti-La, autoantibodies, was mapped
      to a region forming a helix-loop-helix at the apical tip of the Ro 60 molecule.
      Immobilization of this region to the solid phase exposed an epitope that was
      recognized by IgG from primary SS and SLE patients whose sera had both anti-Ro
      and anti-La autoantibodies. Autoantibodies eluted from either the surface of
      apoptotic cells or the Ro 60 epitope on the solid phase were non-cross-reactive
      and specifically recognized membrane-bound or cytoplasmic forms of Ro 60.
      CONCLUSION: This is the first example of a dichotomy of human autoantibody
      responses against mutually exclusive determinants linked to a single domain of a
      systemic autoantigen and supports a model in which tolerance is broken by
      different immunogenic forms of Ro 60.

PMID- 20131296
TI  - High-dose cyclophosphamide versus monthly intravenous cyclophosphamide for
      systemic lupus erythematosus: a prospective randomized trial.
AB  - OBJECTIVE: Monthly intravenous (IV) cyclophosphamide for 6 months has been the
      standard induction regimen for lupus nephritis, followed by a maintenance regimen
      of quarterly infusions for 2 years. We undertook this study to compare the
      efficacy and safety of the standard regimen versus a high-dose IV
      cyclophosphamide regimen. METHODS: We performed a prospective randomized trial
      comparing monthly IV cyclophosphamide at 750 mg/m(2) body surface area for 6
      months followed by quarterly IV cyclophosphamide for 2 years (traditional
      treatment) against high-dose IV cyclophosphamide (50 mg/kg daily for 4 days)
      (high-dose treatment). Entry criteria included renal lupus, neurologic lupus, or
      other organ system involvement with moderate-to-severe activity. RESULTS: Fifty
      one patients were randomized; 3 withdrew before treatment and 1 committed suicide
      after 2 months of high-dose treatment. Twenty-two had renal lupus, 14 had
      neurologic lupus, and 11 had other organ involvement. The outcome measure was the
      Responder Index for Lupus Erythematosus (complete response, partial response, no
      change, or worsening). At 6 months (the end of induction), 11 of 21 patients
      (52%) in the high-dose treatment group had a complete response compared with 9 of
      26 patients (35%) in the traditional treatment group (P = 0.13). At the final
      visit (30 months), 10 of 21 patients (48%) in the high-dose treatment group had a
      complete response compared with 13 of 20 patients (65%) who continued with
      traditional treatment (P = 0.13). Six patients crossed over from traditional
      treatment to high-dose treatment because of lack of response, and 3 of those
      patients became complete responders. CONCLUSION: There was not strong evidence
      that monthly IV cyclophosphamide and high-dose IV cyclophosphamide differed in
      complete or in any (complete or partial) response to induction or maintenance
      therapy. However, nonresponders to monthly IV cyclophosphamide can sometimes be
      rescued with high-dose IV cyclophosphamide.

PMID- 20131297
TI  - Nucleic acid metabolism and systemic autoimmunity revisited.

PMID- 20131302
TI  - Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive
      acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study.
AB  - Dasatinib 70 mg twice daily is indicated for Philadelphia chromosome-positive
      acute lymphoblastic leukemia (Ph+ ALL) intolerant or resistant to imatinib. In
      patients with chronic-phase chronic myelogenous leukemia, once-daily dosing has
      similar efficacy with improved safety, compared with twice-daily dosing. A phase
      3 study (n = 611) assessed the efficacy and safety of dasatinib 140 mg once daily
      versus 70 mg twice-daily in patients with advanced phase chronic myelogenous
      leukemia or Ph+ ALL resistant or intolerant to imatinib. Here, results from the
      Ph+ ALL subset (n = 84) with a 2-year follow-up are reported. Patients were
      randomly assigned to receive dasatinib either 140 mg once daily (n = 40) or 70 mg
      twice daily (n = 44). The rate of confirmed major hematologic response with once
      daily dosing (38%) was similar to that with twice-daily dosing (32%). The rate of
      major cytogenetic response with once-daily dosing (70%) was higher than that with
      twice-daily dosing (52%). Compared with the twice-daily schedule, the once-daily
      schedule had longer progression-free survival (median, 3.0 months versus 4.0
      months, respectively) and shorter overall survival (median, 9.1 months versus 6.5
      months, respectively). Overall safety profiles were similar between two groups,
      with nonhematologic adverse events being mostly grade 1 or 2. Pleural effusion
      was less frequent with once-daily dosing than with twice-daily dosing (all
      grades, 18% versus 32%). Notably, none of the differences between the two
      schedules was statistically significant. Compared with the 70 mg twice daily,
      dasatinib 140 mg once daily had similar overall efficacy and safety in patients
      with imatinib-resistant or intolerant Ph+ ALL. (clinicaltrials.gov identifier:
      NCT00123487).

PMID- 20131303
TI  - The incidence of immune thrombocytopenic purpura in children and adults: A
      critical review of published reports.
AB  - Reports of the incidence of ITP are few and their methodology is variable.
      Accurate estimates of the incidence of immune thrombocytopenic purpura (ITP) are
      important to understand the medical and public health impact of the disease. To
      critically review all published reports on the incidence of ITP in children and
      adults, all articles identified on the Medline database (searched January 1, 1966
      August 7, 2009) that reported data on the incidence of ITP were retrieved.
      Articles which directly estimated the incidence of ITP were selected for review.
      Eight articles reported the incidence of acute ITP in children. After review,
      four were determined to have the strongest estimates, based on the method of
      patient identification and study design. The lowest incidence estimate in these
      four studies was 2.2 per 10(5) children/year (95% confidence interval 1.9, 2.4)
      and the highest incidence estimate was 5.3 per 10(5) children/year (95%
      confidence interval 4.3, 6.4). Three studies reported the incidence of ITP in
      adults. The estimate from the article with the strongest methodology reported an
      incidence estimate of 3.3 per 10(5) adults/year. The current strongest estimate
      of the incidence of acute ITP in children is between 1.9 and 6.4 per 10(5)
      children/year; for adults the current strongest estimate of the incidence of ITP
      is 3.3 per 10(5) adults/year. An important limitation of these studies is that
      they are primarily from Europe and may not be generalizable to all regions.

PMID- 20131304
TI  - Host immunity affects survival in myelodysplastic syndromes: Independent
      prognostic value of the absolute lymphocyte count.
AB  - The prognostic significance of the peripheral blood absolute lymphocyte count
      (ALC) has been carefully examined in lymphoid malignancies, but the importance of
      the baseline ALC in chronic myeloid neoplasms is less clear. In a recent analysis
      of myelodysplastic syndromes (MDS) associated with deletion of chromosome 5q, we
      observed that an ALC < 1.2x 10(9) cells/L at diagnosis is independently
      associated with poorer survival. Clinicopathological data from 503 patients with
      non-del(5q) MDS evaluated at Mayo Clinic between 1996 and 2007 were reviewed to
      determine the prognostic impact of ALC at diagnosis in non-del(5q) MDS. Patients
      with MDS and an ALC at diagnosis > or =1.2x 10(9) (N = 248) experienced a
      superior overall survival (OS) compared with patients with an ALC < 1.2x 10(9)/L
      (N = 255, median OS of 26.6 months versus 18.5 months, P < 0.001, respectively).
      ALC at diagnosis was an independent predictor for OS when compared with the
      International Prognostic Scoring System and the WHO-based Prognostic Scoring
      System. This study suggests that ALC at diagnosis is a prognostic factor for OS
      in MDS, and argues in favor of further studies to assess the role of host
      immunity in MDS clinical outcomes.

PMID- 20131307
TI  - Treatment of Philadelphia-positive acute lymphocytic leukemia with tyrosine
      kinase inhibitors: What is the optimal regimen?

PMID- 20131308
TI  - Fatal bone marrow embolism in a child with hemoglobin SE disease.

PMID- 20131309
TI  - Laboratory monitoring of new anticoagulants.
AB  - Maintaining a balance between bleeding and clotting has always been a challenge
      in treating coagulation disorders. A perturbation in that balance can be
      associated with substantial morbidity and mortality. As a result, anticoagulant
      monitoring is extremely important, and inappropriate testing may lead to
      complications. There are now a variety of new anticoagulant drugs in clinical use
      including several direct thrombin inhibitors (DTIs), such as argatroban,
      bivalirudin, and hirudin, as well as a Factor Xa inhibitor, fondaparinux. There
      are pitfalls associated with some of the currently used laboratory monitoring
      tests, and newer alternative laboratory monitoring tests have been investigated
      (Walenga and Hoppensteadt, Semin Thromb Hemost 2004;30:683-695). In addition,
      laboratory testing can assist with transitioning patients from DTI to warfarin
      therapy.

PMID- 20131310
TI  - Genetic polymorphisms in cytochrome P450s, GSTs, NATs, alcohol consumption and
      risk of non-Hodgkin lymphoma.
AB  - The aim of this study was to investigate whether genetic polymorphisms in
      cytochrome P450s (CYPs), glutathione S-transferases (GSTs), and N
      acetyltransferases (NATs) genes modify the relationship between alcohol
      consumption and risk of non-Hodgkin's lymphoma (NHL) in a population-based, case
      control study including 1,115 Connecticut women. Although we did not find strong
      evidence that the genetic polymorphisms modify the relationship between alcohol
      consumption and risk of NHL, we identified significant interactions for multiple
      GSTs and NATs and alcohol intake among persons with DLBCL. Our results confer
      support investigation of the gene-environment interaction in a larger study
      population of DLBCL.

PMID- 20131311
TI  - A new stopping rule for surveys.
AB  - Non-response is a problem for most surveys. In the sample design, non-response is
      often dealt with by setting a target response rate and inflating the sample size
      so that the desired number of interviews is reached. The decision to stop data
      collection is based largely on meeting the target response rate. A recent article
      by Rao, Glickman, and Glynn (RGG) suggests rules for stopping that are based on
      the survey data collected for the current set of respondents. Two of their rules
      compare estimates from fully imputed data where the imputations are based on a
      subset of early responders to fully imputed data where the imputations are based
      on the combined set of early and late responders. If these two estimates are
      different, then late responders are changing the estimate of interest. The
      present article develops a new rule for when to stop collecting data in a sample
      survey. The rule attempts to use complete interview data as well as covariates
      available on non-responders to determine when the probability that collecting
      additional data will change the survey estimate is sufficiently low to justify
      stopping data collection. The rule is compared with that of RGG using simulations
      and then is implemented using data from a real survey.

PMID- 20131312
TI  - Selective cleavage of an azaGly peptide bond by copper(II). Long-range effect of
      histidine residue.
AB  - Several reports have highlighted the interest of replacing Gly, a frequent amino
      acid within bioactive peptides, by azaGly (Agly) to improve their stability,
      activity or for the design of prodrugs. Because metal catalysis is increasingly
      used for tailoring peptide molecules, we have studied the stability of Agly
      peptides in the presence of metal ions. In this study, we show that Cu(II),
      unlike other metal ions such as Fe(II), Fe(III), Pd(II), or Pt(II), induces the
      cleavage of Agly peptides at room temperature and pH 7.3. The cleavage occurred
      in the absence of an anchoring His residue within the peptide but it was
      accelerated when this amino acid was present in the sequence. The influence of
      His residue on the cleavage rate was minimal when His and Agly were adjacent,
      whereas large effects were observed for distant His residues. The reaction
      between Cu(II) and Agly peptides induced the formation of Cu(I) species, which
      could be detected using bicinchoninic acid as a probe. The nature of products
      formed in this reaction allowed suggesting a mechanism for the Cu(II)-induced
      cleavage of Agly peptides.

PMID- 20131313
TI  - Diffusion-weighted imaging of normal fibroglandular breast tissue: influence of
      microperfusion and fat suppression technique on the apparent diffusion
      coefficient.
AB  - The influence of microperfusion and fat suppression technique on the apparent
      diffusion coefficient (ADC) values obtained with diffusion weighted imaging (DWI)
      of normal fibroglandular breast tissue was investigated. Seven volunteers (14
      breasts) were scanned using diffusion weighting factors (b values) up to 1600
      s/mm(2) and the four different fat suppression techniques: STIR, fat saturation,
      SPAIR, and Water Excitation. The relationship between the logarithmic DW
      attenuation curves and b was linear for b values up to 600 s/mm(2) (R(2) >
      0.999). Small differences were noted between the ADC values obtained with the
      various fat suppression methods, especially at the higher b values. Water
      Excitation had the highest mean SNR, exceeding STIR (p = 0.03) though not
      significantly different from fat saturation and SPAIR. In conclusion, the ADC of
      fibroglandular breast tissue is not influenced by microperfusion and Water
      Excitation is recommended because it yielded the best SNR values. These factors
      may be crucial in the differentiation between benign and malignant lesions.

PMID- 20131314
TI  - MGMT activity, promoter methylation and immunohistochemistry of pretreatment and
      recurrent malignant gliomas: a comparative study on astrocytoma and glioblastoma.
AB  - The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a key
      player in tumor cell resistance. Promoter methylation, MGMT activity and
      immunohistochemistry are used for determining the MGMT status. However, it is
      unclear whether MGMT promoter methylation correlates with MGMT activity and
      whether MGMT promoter methylation of the pretreatment tumor predicts the MGMT
      status of recurrences. To address these questions, we determined MGMT activity
      promoter methylation and immunoreactivity in pretreatment and recurrent
      glioblastomas (GB, WHO Grade IV), and in astrocytomas (WHO Grade III). We show
      that GB that were promoter methylated display a range of 0-62 fmol/mg MGMT and
      tumors that were nonmethylated 0-423 fmol/mg protein. For astrocytomas, promoter
      methylated samples displayed 0-28 fmol/mg and, nonmethylated samples, 23-107
      fmol/mg. No correlation was found between the intensity of promoter methylation
      and MGMT activity. Given a threshold level of 30 fmol/mg of protein, we found a
      correlation between promoter methylation and no/low MGMT activity in 82.4% of the
      tumors. This high correlation level was only observed when tumors were excluded
      showing a hemimethylated promoter (20%). Therefore, classification of
      hemimethylated tumors remains questionable. Further, we show that 39.1% of
      pretreatment GB and 5.3% of recurrences were promoter methylated, which is in
      line with the observed increase of MGMT activity in recurrences. Although
      individual exceptions were found, the data show an overall correlation between
      promoter methylation and lack/low MGMT activity in GB and astrocytomas. We also
      show that promoter methylation assay is superior over immunohistochemistry in
      determining the MGMT status defined by a given MGMT activity level.

PMID- 20131315
TI  - Genetic variation of PSCA gene is associated with the risk of both diffuse- and
      intestinal-type gastric cancer in a Chinese population.
AB  - Prostate stem cell antigen (PSCA), a member of the LY-6/Thy-1 family of
      glycosylphosphatidylinositol-anchored cell surface proteins, is considered to be
      involved in the cell-proliferation inhibition and/or cell-death induction
      activity. Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in
      the PSCA gene were recently identified as the susceptibility loci of gastric
      cancer, especially in diffuse type. Therefore, this study was to investigate
      whether these 2 SNPs were associated with the risk of gastric cancer in Chinese
      population. We genotyped rs2976392 and rs2294008 in PSCA in a case-control study
      including 1,053 incident gastric cancer patients and 1,100 cancer-free controls
      in a high-risk Chinese population. We found that variant genotypes of rs2976392
      (GA/AA) were associated with a significantly 37% increased risk of gastric cancer
      (adjusted OR =1.37, 95% CI = 1.15-1.62), compared with variant homozygote GG, and
      the associations were all consistently significant in both intestinal and diffuse
      subtypes, and among different subgroups stratified by age, sex, drinking or
      smoking status. Interestingly, a significant multiplicative interaction between
      rs2976392 (GA/AA) and alcohol drinking was detected on the development of
      intestinal-type gastric cancer (p = 0.009). However, rs2294008 variant genotypes
      (CT/TT) were associated with a nonsignificant increased risk of gastric cancer
      (adjusted OR = 1.14, 95% CI = 0.96-1.36). A small meta-analysis including 5 case
      control studies showed undoubtedly associations between PSCA rs2294008 and
      rs2976392 and gastric cancer risk (OR = 1.83, 95% CI: 1.29-2.60 and OR = 1.84,
      95% CI: 1.33-2.56, respectively). These findings provide further evidence
      supporting that the genetic variants of PSCA gene may contribute to the gastric
      carcinogenesis.

PMID- 20131316
TI  - Pak1 and Pak2 are activated in recurrent respiratory papillomas, contributing to
      one pathway of Rac1-mediated COX-2 expression.
AB  - Recurrent respiratory papillomas are premalignant tumors of the airway caused by
      human papillomaviruses (HPVs), primarily Types 6 and 11. We had reported that
      respiratory papillomas overexpress the epidermal growth factor receptor (EGFR),
      the small GTPase Rac1 and cyclooxygenase-2 (COX-2), and have enhanced nuclear
      factor-kappaB (NFkappaB) activation with decreased levels of IkappaB-beta but not
      IkappaB-alpha. We also showed that EGFR-activated Rac1 mediates expression of COX
      2 through activation of p38 mitogen-activated protein kinase. We have now asked
      whether the p21-activated kinases Pak1 or Pak2 mediate activation of p38 by Rac1
      in papilloma cells. Pak1 and Pak2 were constitutively activated in vivo in
      papilloma tissue compared with normal epithelium, and Rac1 siRNA reduced the
      level of both phospho-Pak1 and phospho-Pak2 in cultured papilloma cells.
      Reduction in Pak1 and Pak2 with siRNA decreased the COX-2 expression in papilloma
      cells, increased the levels of IkappaB-beta and reduced the nuclear localization
      of NF-kappaB, but had no effect on p38 phosphorylation. Our studies suggest that
      Rac1 --> Pak1/Pak2 --> NFkappaB is a separate pathway that contributes to the
      expression of COX-2 in HPV-induced papillomas, independently of the previously
      described Rac1 --> p38 --> COX-2 pathway.

PMID- 20131317
TI  - Characteristic methylation profile in CpG island methylator phenotype-negative
      distal colorectal cancers.
AB  - Aberrant DNA methylation is involved in colon carcinogenesis. Although the CpG
      island methylator phenotype (CIMP) is defined as a subset of colorectal cancers
      (CRCs) with remarkably high levels of DNA methylation, it is not known whether
      epigenetic processes are also involved in CIMP-negative tumors. We analyzed the
      DNA methylation profiles of 94 CRCs and their corresponding normal-appearing
      colonic mucosa with 11 different markers, including the five classical CIMP
      markers. The CIMP markers were frequently methylated in proximal CRCs (p < 0.01);
      however, RASSF1A methylation levels were significantly higher in distal CRCs, the
      majority of which are CIMP-negative (p < 0.05). Similarly, methylation levels of
      RASSF1A and SFRP1 in the normal-appearing mucosae of distal CRC cases were
      significantly higher than those in the proximal CRC cases (p < 0.05). They were
      also positively correlated with age (RASSF1A, p < 0.01; SFRP1, p < 0.01).
      Microarray-based genome-wide DNA methylation analysis of 18 CRCs revealed that
      168 genes and 720 genes were preferentially methylated in CIMP-negative distal
      CRCs and CIMP-positive CRCs, respectively. Interestingly, more than half of the
      hypermethylated genes in CIMP-negative distal CRCs were also methylated in the
      normal-appearing mucosae, indicating that hypermethylation in CIMP-negative
      distal CRCs is more closely associated with age-related methylation. By contrast,
      more than 60% of the hypermethylated genes in CIMP-positive proximal CRCs were
      cancer specific (p < 0.01). These data altogether suggest that CpG island
      promoters appear to be methylated in different ways depending on location, a
      finding which may imply the presence of different mechanisms for the acquisition
      of epigenetic changes during colon tumorigenesis.

PMID- 20131318
TI  - Tumor-specific mutation and downregulation of ING5 detected in oral squamous cell
      carcinoma.
AB  - Our previous study showed high frequency of allelic loss at chromosome 2q37
      region in oral cancer. This location contains several candidate tumor suppressor
      genes such as PPP1R7, ILKAP, DTYMK and ING5. We previously showed 3 members of
      inhibitor of growth (ING) family, ING1, ING3 and ING4 as tumor suppressor gene in
      head and neck cancer. As ING5 shows high homology with other members of ING genes
      including highly conserved carboxy-terminal plant homeodomain and nuclear
      localization signal, we first picked up ING5 and examined it as a possible tumor
      suppressor in oral cancer. For this aim, mutation and mRNA expression status of
      ING5 in paired normal and oral squamous cell carcinoma samples were examined by
      reverse transcription polymerase chain reaction (RT-PCR) and sequencing. Three
      missense mutations located within leucine zipper like (LZL) finger and novel
      conserved region (NCR) domains in ING5 protein were detected, probably abrogating
      its normal function. We also found 5 different alternative splicing variants of
      ING5. Then, we examined mRNA level of ING5 by quantitative real time reverse
      transcription polymerase chain reaction (qRT-PCR) analysis, which demonstrated
      decreased expression of ING5 mRNA in 61% of the primary tumors as compared to the
      matched normal samples. In conclusion, tumor-specific mutation and downregulation
      of ING5 mRNA suggested it as a tumor suppressor gene in oral squamous cell
      carcinoma.

PMID- 20131319
TI  - Exogenous luminal nitric oxide exposure accelerates columnar transformation of
      rat esophagus.
AB  - Exposure of the esophageal mucosa to refluxed gastroduodenal contents is
      recognized to be an important risk factor for Barrett's esophagus (BE). At the
      human gastroesophageal junction, nitric oxide is generated luminally through the
      enterosalivary recirculation of dietary nitrate, and in cases with
      gastroesophageal reflux, the site of luminal nitric oxide generation could shift
      to the distal esophagus. The aim of this study is to investigate whether
      exogenous luminal nitric oxide could promote the development of BE in rats.
      Sodium nitrite plus ascorbic acid were administered to a rat surgical model of
      BE, in which the gastroduodenal contents were refluxed into the esophagus to
      generate exogenous luminal nitric oxide in the esophagus by the acid-catalyzed
      chemical reaction between the 2 reagents. The emergence of BE was evaluated
      histologically in the early phase (several weeks) after the surgery with or
      without exogenous nitric oxide administration. To elucidate the histogenesis of
      BE, CDX2, MUC2 and MUC6 expressions were investigated immunohistochemically.
      Coadministration of sodium nitrite plus ascorbic acid significantly accelerated
      the timing of emergence and increased the area of BE compared with controls.
      Administration of either reagent alone did not show any promotive effects on BE
      formation. Immunohistochemically, the columnar epithelium thus induced was
      similar to the specialized intestinal metaplasia in human BE. The results of this
      animal model study suggest that exogenous luminal nitric oxide could be involved
      in the pathogenesis of the columnar transformation of the esophagus. Further
      studies in human are warranted.

PMID- 20131320
TI  - Visual experience and age affect synaptic organization in the mushroom bodies of
      the desert ant Cataglyphis fortis.
AB  - Desert ants of the genus Cataglyphis undergo an age-related polyethism from
      interior workers involved in brood care and food processing to short-lived
      outdoor foragers with remarkable visual navigation capabilities. The quick
      transition from dark to light suggests that visual centers in the ant's brain
      express a high degree of plasticity. To investigate structural synaptic
      plasticity in the mushroom bodies (MBs)-sensory integration centers supposed to
      be involved in learning and memory-we immunolabeled and quantified pre- and
      postsynaptic profiles of synaptic complexes (microglomeruli, MG) in the visual
      (collar) and olfactory (lip) input regions of the MB calyx. The results show that
      a volume increase of the MB calyx during behavioral transition is associated with
      a decrease in MG numbers in the collar and, less pronounced, in the lip. Analysis
      of tubulin-positive profiles indicates that presynaptic pruning of projection
      neurons and dendritic expansion in intrinsic Kenyon cells are involved. Light
      exposure of dark-reared ants of different age classes revealed similar effects.
      The results indicate that this structural synaptic plasticity in the MB calyx is
      primarily driven by visual experience rather than by an internal program. This is
      supported by the fact that dark-reared ants age-matched to foragers had MG
      numbers comparable to those of interior workers. Ants aged artificially for up to
      1 year expressed a similar plasticity. These results suggest that the high degree
      of neuronal plasticity in visual input regions of the MB calyx may be an
      important factor related to behavior transitions associated with division of
      labor.

PMID- 20131321
TI  - Journal of Traumatic Stress. PTSD 30 years on.

PMID- 20131322
TI  - Amino acid delta13C analysis of hair proteins and bone collagen using liquid
      chromatography/isotope ratio mass spectrometry: paleodietary implications from
      intra-individual comparisons.
AB  - We report a novel method for the chromatographic separation and measurement of
      stable carbon isotope ratios (delta(13)C) of individual amino acids in hair
      proteins and bone collagen using the LC-IsoLink system, which interfaces liquid
      chromatography (LC) with isotope ratio mass spectrometry (IRMS). This paper
      provides baseline separation of 15 and 13 of the 18 amino acids in bone collagen
      and hair proteins, respectively. We also describe an approach to analysing small
      hair samples for compound-specific analysis of segmental hair sections. The
      LC/IRMS method is applied in a historical context by the delta(13)C analysis of
      hair proteins and bone collagen recovered from six individuals from Uummannaq in
      Greenland. The analysis of hair and bone amino acids from the same individual,
      compared for the first time in this study, is of importance in palaeodietary
      reconstruction. If hair proteins can be used as a proxy for bone collagen at the
      amino acid level, this validates compound-specific isotope studies using hair as
      a model for palaeodietary reconstruction. Our results suggest that a small offset
      observed in the bulk delta(13)C values of the hair and bone samples may be
      attributed to two factors: (i) amino acid compositional differences between hair
      and bone proteins, and (ii) differential turnover rates of the tissues and the
      amino acid pools contributing to their synthesis. This application proposes that
      hair may be a useful complementary or alternative source of compound-specific
      paleodietary information.

PMID- 20131323
TI  - Identification of N-glycans from Ebola virus glycoproteins by matrix-assisted
      laser desorption/ionisation time-of-flight and negative ion electrospray tandem
      mass spectrometry.
AB  - The larger fragment of the transmembrane glycoprotein (GP1) and the soluble
      glycoprotein (sGP) of Ebola virus were expressed in human embryonic kidney cells
      and the secreted products were purified from the supernatant for carbohydrate
      analysis. The N-glycans were released with PNGase F from within sodium dodecyl
      sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) gels. Identification of
      the glycans was made with normal-phase high-performance liquid chromatography
      (HPLC), matrix-assisted laser desorption/ionisation mass spectrometry, negative
      ion electrospray ionisation fragmentation mass spectrometry and exoglycosidase
      digestion. Most glycans were complex bi-, tri- and tetra-antennary compounds with
      reduced amounts of galactose. No bisected compounds were detected. Triantennary
      glycans were branched on the 6-antenna; fucose was attached to the core GlcNAc
      residue. Sialylated glycans were present on sGP but were largely absent from GP1,
      the larger fragment of the transmembrane glycoprotein. Consistent with this was
      the generally higher level of processing of carbohydrates found on sGP as
      evidenced by a higher percentage of galactose and lower levels of high-mannose
      glycans than were found on GP1. These results confirm and expand previous
      findings on partial characterisation of the Ebola virus transmembrane
      glycoprotein. They represent the first detailed data on carbohydrate structures
      of the Ebola virus sGP.

PMID- 20131324
TI  - Effects of nicotine on pulmonary surfactant proteins A and D in ovine lung
      epithelia.
AB  - Maternal smoking during pregnancy increases the incidence and severity of
      respiratory infections in neonates. Surfactant proteins A and D (SP-A and SP-D,
      respectively) are components of pulmonary innate immunity and have an important
      role in defense against inhaled pathogens. The purpose of this study was to
      determine if nicotine exposure during the third trimester of pregnancy alters the
      expression of SP-A and SP-D of fetal lung epithelia. Pregnant ewes were assigned
      to four groups; a nicotine-exposed full-term and pre-term group, and control full
      term and pre-term group. Lung tissue was collected for Western blot and IHC
      analysis of SP-A level, Western blot analysis of SP-D level and qPCR analysis of
      SP-A and SP-D mRNA expression. Exposure to nicotine significantly decreased SP-A
      gene expression (P = 0.01) and SP-A protein level in pre-term lambs. This finding
      suggests that maternal nicotine exposure during the last trimester of pregnancy
      alters a key component of lung innate immunity in offspring.

PMID- 20131325
TI  - MS characterization of qualitative protein polymorphisms in the spinal cords of
      inbred mouse strains.
AB  - The spinal cord proteomes of two inbred mouse strains with different
      susceptibility to experimental autoimmune encephalomyelitis (EAE), a mouse model
      of multiple sclerosis, were investigated by 2-DE and MALDI-MS. A proteome map
      comprising 304 different protein species was established. Using 2-D fluorescence
      difference gel electrophoresis, a comparison of the mouse strains revealed 26
      qualitatively polymorphic proteins with altered electrophoretic mobility. MS
      analyses and DNA sequencing were applied to characterize their structural
      differences and 14 single amino acid substitutions were identified. Moreover,
      analysis of selectively enriched phosphopeptides from the neurofilament heavy
      polypeptide of both mouse strains revealed a high degree of diversity in the
      phosphorylated C-terminal domains of this protein. The described approach is
      capable to structurally characterize qualitative protein polymorphisms, whereas
      their functional significance remains to be elucidated. For some proteins
      formerly associated with experimental autoimmune encephalomyelitis and/or
      multiple sclerosis structural polymorphisms are described here, which may be
      subjected to further investigations. In addition, this work should be of general
      interest for proteomic analysis of inbred strains, because it shows potentials
      and constraints in the use of 2-DE analysis and MALDI-MS to detect and
      characterize structural protein polymorphisms.

PMID- 20131326
TI  - Gilthead sea bream liver proteome altered at low temperatures by oxidative
      stress.
AB  - Gilthead sea bream exposed to the cold show multiple physiological alterations,
      particularly in liver. A typical cold-stress response was reproduced in gilthead
      sea bream acclimated to 20 degrees C (Warm group) when the water temperature was
      lowered to 8 degrees C (Cold group). After 10 days, thiobarbituric acid reactive
      substances in the liver had increased by 50%, and nitric oxide had increased
      twofold. This indicates that lipid peroxidation and oxidative stress had
      occurred. Protein profiles of liver from fish in warm and cold environments were
      obtained by 2-DE. Quantification of differential expression by matching spots
      showed that a total of 57 proteins were altered significantly. Many proteins were
      downregulated following cold exposure, including actin, the most abundant protein
      in the proteome; enzymes of amino acid metabolism; and enzymes with antioxidant
      capacity, such as betaine-homocysteine-methyl transferase, glutathione-S
      transferase and catalase. Some proteins associated with protective action were
      upregulated at low temperatures, including peroxiredoxin, thioredoxin and
      lysozyme; as well as enzymes such as aldehyde dehydrogenase and adenosin
      methionine synthetase. However, the upregulation of proteases, proteasome
      activator protein and trypsinogen-like protein indicated an increase in
      proteolysis. Increases in elongation factor-1alpha, the GAPDH oxidative form,
      tubulin and Raf-kinase inhibitor protein indicated oxidative stress and the
      induction of apoptosis. These data indicate that cold exposure induced oxidative
      damage in hepatocytes.

PMID- 20131327
TI  - Efficient evaluation of ranking procedures when the number of units is large,
      with application to SNP identification.
AB  - Simulation-based assessment is a popular and frequently necessary approach for
      evaluating statistical procedures. Sometimes overlooked is the ability to take
      advantage of underlying mathematical relations and we focus on this aspect. We
      show how to take advantage of large-sample theory when conducting a simulation
      using the analysis of genomic data as a motivating example. The approach uses
      convergence results to provide an approximation to smaller-sample results,
      results that are available only by simulation. We consider evaluating and
      comparing various ranking-based methods for identifying the most highly
      associated SNPs in a genome-wide association study, derive integral equation
      representations of the pre-posterior distribution of percentiles produced by
      three ranking methods, and provide examples comparing performance. These results
      are of interest in their own right and set the framework for a more extensive set
      of comparisons.

PMID- 20131328
TI  - Validation of ischemic cerebrovascular diagnoses in the health improvement
      network (THIN).
AB  - PURPOSE: To evaluate the validity of recorded diagnoses of ischemic
      cerebrovascular events requiring hospitalization within The Health Improvement
      Network (THIN) UK primary care database. METHODS: We identified 15 397
      individuals aged 40-84 years with a first recorded ischemic event in 2000-2004.
      Of these, 4239 had a code suggestive of a hospitalization within 2 weeks of the
      event. A three-step strategy was used to validate the records of these patients:
      manual review of computerized medical records excluding free-text comments;
      manual review including free-text comments (which include information gained from
      specialists, hospital discharge letters and results of diagnostic tests) of a
      random sample of possible cases (n = 300) and non-cases (n = 100); and review of
      full medical records of this random sample and a questionnaire completed by their
      primary care physician. The positive predictive value (PPV) of each step was
      calculated. The confirmation rate was used to estimate incidence in the general
      population. RESULTS: After step 1, 3447 individuals were classified as possible
      cases and 792 were excluded as non-cases. After step 2, 82% of possible cases
      were still classified as such. Step 3 showed that inclusion of free-text comments
      increased the PPV of a diagnosis from 76 to 86%. The weighted incidence of
      hospitalized ischemic cerebrovascular events was 1.73 per 1000 person-years (95%
      CI:1.68-1.77). CONCLUSIONS: THIN demonstrates a high validity for the study of
      ischemic cerebrovascular events when reviewing computer records with additional
      free-text comments. Accuracy of hospitalization status was not as well recorded.

PMID- 20131329
TI  - Obstetric morbidity associated with amniotic sheets.
AB  - OBJECTIVE: The objective of this study was to determine whether amniotic sheets
      are associated with an increase in obstetric and neonatal morbidity. METHODS:
      Using a cohort study design, we identified all women with amniotic sheets,
      detected by a second-trimester ultrasound examination at a university hospital
      over a 6-year period. All women who received an ultrasound examination during
      that time, without a diagnosis of amniotic sheets, were also identified, and two
      women from among this group were randomly selected as controls for each case.
      Maternal and neonatal data were abstracted from the medical records, and maternal
      and neonatal morbidity were compared between the two groups. RESULTS: One hundred
      and twenty-two women with pregnancies with a diagnosis of amniotic sheets were
      identified and compared to 244 women with pregnancies without a diagnosis of
      amniotic sheets. Composite obstetric morbidity was higher in women with amniotic
      sheets: 21.3% vs. 8.2% (relative risk (RR) 2.6; 95% CI, 1.5-4.5). Additionally,
      in women with amniotic sheets, neonates were more likely to be born with a birth
      weight of < 2500 g (RR 3.3; 95% CI, 1.8-6.4) and were more likely to be admitted
      to the neonatal intensive care unit (RR 2.3; 95% CI, 1.3-4.3). There were no
      perinatal deaths observed in either group. CONCLUSION: Amniotic sheets are
      associated with an increase in adverse obstetric outcomes.

PMID- 20131330
TI  - Cervicovaginal fistula presenting during miscarriage.
AB  - Cervicovaginal fistula is a recognized complication of induced mid-trimester
      termination of pregnancy, but more recently it has also been recognized as
      representing a complication of prior cervical cerclage. We report the ultrasound
      findings of prolapse of the amniotic sac through a cervicovaginal fistula in a
      woman with prior cervical cerclage. A woman with cervical incompetence and prior
      failed McDonald cerclage presented for prophylactic Shirodkar cerclage. Before
      the procedure, transvaginal ultrasonography revealed a live intrauterine
      pregnancy at 14 weeks' gestation. Upon further ultrasound examination, the
      amniotic sac appeared to protrude through the posterior wall of the cervix into
      the vaginal vault. Pelvic examination verified prolapse of the amniotic sac
      through a cervicovaginal fistula. The patient underwent an uncomplicated
      dilatation and evacuation. Women with a history of cervical cerclage are at risk
      for the development of cervicovaginal fistula, the detection of which is
      important to prevent potential morbidity.

PMID- 20131331
TI  - Fetal thymus size in uncomplicated twin and singleton pregnancies.
AB  - OBJECTIVES: The main objective of this study was to determine whether fetal
      thymic measurements could be obtained in twins, with a secondary goal to
      determine whether thymic measurements from uncomplicated singleton and twin
      pregnancies are comparable. METHODS: The transverse diameter and perimeter of the
      fetal thymus were measured prospectively in 678 singleton and 56 twin
      pregnancies, and their relationships with gestational age were determined and
      compared between groups. RESULTS: Thymic measurements were possible in 757
      (95.8%) of the 790 fetuses. Measurements were not possible in 19 of 678
      singletons (2.8%) and in 14 of the 112 (12.5%) twins (P < 0.001). After
      construction of nomograms for the transverse diameter and perimeter of the fetal
      thymus, similar measurements were noted for singletons and twins. CONCLUSIONS:
      These results suggest that sonographic measurements of the thymus are feasible in
      twin pregnancies and that, in uncomplicated pregnancies, these measurements are
      similar to those noted for singletons. These findings pave the way for future
      studies aimed at determining the clinical utility of thymic measurements in
      complicated singleton and twin pregnancies.

PMID- 20131332
TI  - Intra-amniotic N-terminal pro-brain natriuretic peptide in severe twin-to-twin
      transfusion syndrome treated by fetoscopic laser coagulation.

PMID- 20131333
TI  - Growth of fetal lean mass and fetal fat mass in gestational diabetes.
AB  - OBJECTIVES: This study was carried out to investigate growth indicators of fetal
      lean mass and fat mass in the second half of the gestational period in
      pregnancies complicated by gestational diabetes mellitus (GDM) in comparison to
      normal control pregnancies. METHODS: Forty-three control and 171 GDM pregnancies
      were followed longitudinally by ultrasound examinations, measuring both
      traditional biometric parameters and six non-traditional parameters for the
      evaluation of lean and fat mass. A mixed linear model derived from the log-Count
      function was used to model fetal growth and to make comparisons between groups.
      Factor analysis was used to evaluate the associations between gestational
      diabetes and fetal size and fetal fat/lean mass ratios. RESULTS: A total of 506
      scans were obtained in the 214 pregnancies, a mean of 2.4 scans per pregnancy
      (range 2-5). Maternal age, prepregnancy weight and body mass index were
      significantly higher in GDM pregnancies. Fetuses of GDM pregnancies showed
      greater growth, at the same gestational age, for each lean and fat non
      traditional parameter, having a significantly greater amount of total tissue mass
      and a higher fat mass/lean mass ratio, independent of gestational age, in
      comparison to control pregnancies. CONCLUSIONS: A non-invasive, repeatable
      evaluation of fetal body composition in utero could represent a useful method for
      the early detection of growth abnormalities and for direct estimation of the
      fetal metabolic status.

PMID- 20131334
TI  - Learning curve for lung area to head circumference ratio measurement in fetuses
      with congenital diaphragmatic hernia.
AB  - OBJECTIVE: To assess the learning curve for the fetal lung area to head
      circumference ratio (LHR) calculation in fetuses with congenital diaphragmatic
      hernia (CDH). METHODS: Three trainees with the theoretical knowledge, but without
      prior experience in the LHR measurement, were selected. Each trainee and one
      experienced examiner measured the observed to expected (O/E)-LHR in the lung
      contralateral to the side of the hernia by two methods-manual tracing of lung
      borders and multiplication of the longest diameters-in a cohort of 95 consecutive
      CDH fetuses. The average difference between the three trainees and the expert in
      the O/E-LHR measurement was calculated. A difference below 10% was considered to
      indicate an accurate measurement. The average learning curve was delineated using
      cumulative sum analysis (CUSUM). RESULTS: The CUSUM plots demonstrate that the
      learning curve was achieved by 77 and 72 tests performed for the area obtained by
      the manual-tracing and multiplication-of-the-longest-diameter methods,
      respectively. CONCLUSION: The minimum number of scans required for an
      inexperienced trainee to become competent in examining the LHR is on average 70.

PMID- 20131335
TI  - Administration of nonviral gene vector encoding rat beta-defensin-2 ameliorates
      chronic Pseudomonas aeruginosa lung infection in rats.
AB  - BACKGROUND: Beta-defensin-2 (BD-2) plays an important role in host defense
      against pathogenic microbe challenge by its direct antimicrobial activity and
      immunomodulatory functions. The present study aimed to determine whether genetic
      up-regulation of rat BD-2 (rBD-2) could ameliorate chronic Pseudomonas aeruginosa
      lung infection in rats. METHODS: Plasmid-encoding rBD-2 was delivered to lungs in
      vivo using linear polyethylenimine at 48 h before challenging with seaweed
      alginate beads containing P. aeruginosa. Macroscopic and histopathological
      changes of the lungs, bacterial loads, inflammatory infiltration, and the levels
      of cytokines/chemokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)
      alpha, kertinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP
      2)] were measured at 3 and 7 days post-infection (p.i.). RESULTS: The
      overexpression of rBD-2 resulted in a significant increase in animal survival
      rate (at 3 days p.i.), a significant decrease in bacterial loads in the lungs (at
      3 and 7 days p.i.), and significantly milder lung pathology. In addition, the
      overexpression of rBD-2 led to increased infiltration of polymorphonuclear
      neutrophils (PMN), and elevated protein expression of cytokines/chemokines (IL
      1beta, TNF-alpha, KC and MIP-2) at the early stage of infection (at 3 days p.i.),
      at the same time as being dramatically decreased at the later stage of infection
      (at 7 days p.i.). CONCLUSIONS: Genetic up-regulation of rBD-2 increased animal
      survival rate, and reduced bacterial loads in lungs after bacterial infection.
      The overexpression of rBD-2 also modulated the production of several
      cytokines/chemokines and increased PMN recruitment at the early stage of
      infection. Our findings indicate that the enhancement of BD-2 may be an
      efficacious intervention for chronic P. aeruginosa lung infection.

PMID- 20131336
TI  - The impact of metabolic syndrome on left ventricular myocardial performance.
AB  - BACKGROUND: Metabolic syndrome (MetS) is common and is associated with increased
      cardiovascular morbidity and mortality. Recent prospective studies suggested that
      MetS is associated with increased risk of heart failure. In the present cross
      sectional study, we examined the association between left ventricular myocardial
      performance with MetS. MATERIALS AND METHODS: A total of 550 non-diabetic
      subjects, 275 without MetS and 275 with MetS, matched for gender, age and body
      mass index and free of clinically apparent macrovascular disease were studied.
      MetS was diagnosed using the NCEP-ATP III criteria. Left ventricular myocardial
      performance was assessed using the Tei index. RESULTS: Both men and women with
      MetS had higher values of the Tei index, indicating worse myocardial performance,
      in comparison with those without MetS (p < 0.001). Participants with a cluster of
      more components of the MetS had higher Tei index values than those with fewer
      components of the MetS. In addition, among normotensive subjects, those with MetS
      had significantly higher Tei index values than subjects without MetS.
      Multivariate linear regression analysis, after adjustment for age and body mass
      index, demonstrated that MetS status and from the individual components of the
      MetS, high fasting blood glucose levels, higher blood pressure, low high density
      lipoprotein levels and high waist circumference were associated with worse
      myocardial performance. CONCLUSION: MetS is associated with subclinical
      myocardial dysfunction in both men and women. Strategies to reduce the
      cardiovascular burden and the risk of heart failure associated with MetS should
      aim at prevention of the MetS and its related conditions.

PMID- 20131337
TI  - Can adverse neonatal outcome be predicted in late preterm or term fetal growth
      restriction?
AB  - OBJECTIVE: To identify independent predictors of adverse neonatal outcome in
      cases of fetal growth restriction (FGR) at > or = 34 weeks. METHODS: From a
      cohort of 481 FGR cases delivered at > or = 34 weeks, demographic and obstetric
      variables, fetal biometry and Doppler indices of the uterine, umbilical and fetal
      middle cerebral arteries available within 2 weeks of delivery, were related to
      adverse neonatal outcome, defined as admission to the neonatal intensive care
      unit for indications other than low birth weight alone. RESULTS: Logistic
      regression analysis showed that gestational age (GA) at delivery (odds ratio (OR)
      = 0.59; 95% CI, 0.50-0.70), abdominal circumference (AC) centile (OR = 0.69; 95%
      CI, 0.59-0.81) and umbilical artery (UA) pulsatility index (PI) centile (OR =
      1.02; 95% CI, 1.01-1.04) significantly correlated with adverse neonatal outcome.
      From this model we calculated a score of adverse neonatal outcome expressed by
      the formula: (UA-PI centile/3) - (10 x AC centile) + (10 x (40 - GA at delivery
      in weeks)). Receiver-operating characteristics curve analysis demonstrated that a
      score of > or = 25 optimally predicted adverse neonatal outcome (sensitivity of
      75%, false-positive rate of 18%). Beyond 37.5 weeks, gestational age no longer
      had an independent impact on outcome. CONCLUSIONS: In late preterm or term FGR,
      GA at delivery is the most important predictor of adverse neonatal outcome. At >
      37.5 weeks, delivery may be the best option to minimize adverse outcome in all
      FGR cases. At 34-37 weeks, a score based on GA at delivery, UA-PI centile and AC
      centile optimally predicts adverse neonatal outcome.

PMID- 20131338
TI  - Tei index to assess fetal cardiac performance in fetuses at risk for fetal
      inflammatory response syndrome.
AB  - OBJECTIVES: To examine, in patients with premature rupture of the amniotic
      membranes (PROM) at < 34 weeks of gestation, the relationship between fetal
      myocardial performance measured by the Tei index and fetal inflammatory response
      syndrome (FIRS). METHODS: A case-control study was conducted including 15 preterm
      PROM patients with gestational age between 24 and 33 weeks admitted to Hospital
      de Clinicas de Porto Alegre, and 15 controls with the same gestational age range.
      Fetal echocardiography with Doppler was performed at admission for the preterm
      PROM group, with serial examinations every 7-10 days thereafter until delivery,
      and at the time of inclusion in the control group. Flow velocity waveforms were
      obtained for the left ventricle, from which the Tei index was calculated.
      Placental histopathology and perinatal outcome were compared between the groups.
      RESULTS: The left ventricular Tei index was significantly greater in fetuses with
      preterm PROM compared with controls (0.63 +/- 0.13 vs. 0.51 +/- 0.10, P = 0.007).
      While there was no difference in isovolumetric times, the left ventricular
      ejection time was significantly shorter in the preterm PROM group (164 +/- 17 ms
      vs. 184 +/- 16 ms, P = 0.003). In the preterm PROM group, neonatal sepsis was
      diagnosed in 73.3%, and funisitis and chorionic vasculitis confirmed FIRS in
      53.3%, compared with 6.7% for these three diagnoses in controls (P = 0.001).
      CONCLUSIONS: These data provide further evidence that cardiac dysfunction is
      present in the setting of preterm PROM. The study of myocardial performance with
      the Tei index is a novel non-invasive approach to assess cardiac function and
      monitor the fetus affected with FIRS.

PMID- 20131339
TI  - Reliability of fetal cardiac volumetry using spatiotemporal image correlation:
      assessment of in-vivo and in-vitro measurements.
AB  - OBJECTIVE: To assess the reliability of measurement of fetal cardiac ventricular
      volume, stroke volume, and ejection fraction with four-dimensional ultrasound
      using spatiotemporal image correlation (STIC). METHODS: Volume datasets were
      collected from two sources: 24 from fetuses over a range of gestational ages and
      12 from a miniature balloon model. Datasets were analyzed by three observers,
      repeatedly in 12 fetal datasets and all balloon datasets. Volume calculations
      were obtained by manually tracing multiple parallel slices (three-dimensional
      (3D) slice method). Measurement error was assessed by calculating standard errors
      of measurement (SEM) and coefficients of variation (CV). Reliability was assessed
      by calculating interobserver and intraobserver intraclass correlation
      coefficients (ICC). RESULTS: Measurement errors of balloon volumes were small and
      reliability was good (SEM <or= 0.07 mL, ICC 0.98-1.00). Fetal ventricle volume
      measurement error ranged from 0.09 to 0.20 mL and CV from 14.6 to 28.3%.
      Ventricular volume reliabilities for intra- and interobserver comparisons were
      greater than or equal to 0.94 and 0.75, respectively. Fetal stroke volume
      measurement error (SEM 0.17 mL), CV (21.9%) and reliability were measured
      (intraobserver ICC: left ventricle stroke volume (LVSV), 0.93 vs. right ventricle
      stroke volume (RVSV), 0.88; interobserver ICC: LVSV, 0.75 vs. RVSV, 0.86). The
      measurement error decreased with increasing operator experience. The reliability
      of ejection fraction calculations was poor (ICC < 0.7) for intra- and
      interobserver comparisons. CONCLUSIONS: Volume measurements obtained with STIC
      and 3D slice methods using a balloon model were reliable. In the fetus,
      measurement errors decreased with increasing operator experience, and reliability
      was better for stroke volume than for ejection fraction.

PMID- 20131340
TI  - Umbilical cord cysts in the second and third trimesters: significance and
      prenatal approach.
AB  - OBJECTIVES: This study was carried out to determine the prognosis, and the
      clinical approach, in fetuses with umbilical cord cysts, during the second and
      third trimesters of gestation, according to our experience and data in the
      current literature. METHODS: We identified 10 fetuses with umbilical cord cysts
      that were diagnosed during the second and third trimesters of pregnancy at three
      referral centers. All underwent detailed ultrasound evaluation at the time of
      diagnosis and during follow-up. Prenatal karyotype testing was offered to all
      women. A MEDLINE review of the literature published from 1980 to 2009 was carried
      out to identify previous studies and case reports of fetuses with umbilical cord
      cysts. RESULTS: In our series of 10 cases, significant additional abnormalities
      were observed in two during a detailed sonogram. In one case, trisomy 18 was
      diagnosed, leading to pregnancy termination, and in the other case a neonate with
      heart defects and a normal karyotype was born. These results differ from those
      reported in the literature, in which the association between second- and third
      trimester umbilical cord cysts and fetal anomalies ranged from 38 to 100%.
      CONCLUSIONS: In our study, as in other publications, an association was found
      between the presence of second- and third-trimester umbilical cord cysts and
      fetal anomalies. The strong association between second- and third-trimester
      umbilical cord cysts and aneuploidy in the literature seems to be biased, mainly
      because of the tendency to report abnormal cases. When these findings are
      accompanied by additional sonographic abnormalities, the association with
      aneuploidy is clear and should be an indication for fetal karyotype testing.

PMID- 20131341
TI  - Guidelines for the placement of fiducial points in image-guided neurosurgery.
AB  - BACKGROUND: Point-pair registration is widely used to register the patient and
      the image space in image-guided neurosurgery. The registration accuracy at the
      target point is influenced by the distribution of the fiducial points, and it is
      not always easy to achieve a good distribution in clinical practice. METHODS: We
      propose one original configuration and three variants of the distribution of the
      fiducial points, in which each fiducial point has a definite position on the head
      surface. These configurations are conceived by considering both the theoretical
      value of the target registration error (TRE) and practical constraints on the
      positioning of the fiducial points. These configurations can guide the surgeon to
      place fiducial points directly onto the patient's head. RESULTS: Experiments with
      real clinical data showed that when using the original configuration, the TRE in
      the whole skull was < 2 mm and the TRE in the whole brain was < 1.5 mm if the
      fiducial registration error was 2.5 mm. When using variants of the original
      configuration, small TRE can also be achieved in the corresponding surgical
      field. CONCLUSIONS: This study provides an easy-to-use approach to achieving good
      distribution of fiducial points in image-guided neurosurgery.

PMID- 20131343
TI  - Femtogram-controlled synthesis and self-aligned fabrication of polyaniline micro-
      and nanostructures.

PMID- 20131344
TI  - Combined transition-metal- and organocatalysis: an atom economic C3 homologation
      of alkenes to carbonyl and carboxylic compounds.
AB  - A combination of regioselective room-temperature/ambient-pressure
      hydroformylation (transition-metal catalysis) and decarboxylative Knoevenagel
      reactions (organocatalysis) allowed for the development of an efficient, one-pot
      C3 homologation of terminal alkenes to (E)-alpha,beta-unsaturated acids and
      esters, (E)-beta,gamma-unsaturated acids, (E)-alpha-cyano acrylic acids, and
      alpha,beta-unsaturated nitriles. All reactions proceed under mild conditions,
      tolerate a variety of functional groups, and furnish unsaturated carbonyl
      compounds in good yields and with excellent regio- and stereocontrol. Further, an
      iterative C2 homologation of (E)-alpha,beta-unsaturated carboxylic acids is
      possible through a combination of decarboxylative hydroformylation employing a
      supramolecular catalyst followed by decarboxylative Knoevenagel condensation with
      an organocatalyst.

PMID- 20131345
TI  - Fluorescent 'twist-on' sensing by induced-fit anion stabilisation of a planar
      chromophore.

PMID- 20131346
TI  - Polyoxometalates: building blocks for functional nanoscale systems.
AB  - Polyoxometalates (POMs) are a subset of metal oxides that represent a diverse
      range of molecular clusters with an almost unmatched range of physical properties
      and the ability to form dynamic structures that can range in size from the nano-
      to the micrometer scale. Herein we present the very latest developments from
      synthesis to structure and function of POMs. We discuss the possibilities of
      creating highly sophisticated functional hierarchical systems with multiple,
      interdependent, functionalities along with a critical analysis that allows the
      non-specialist to learn the salient features. We propose and present a "periodic
      table of polyoxometalate building blocks". We also highlight some of the current
      issues and challenges that need to be addressed to work towards the design of
      functional systems based upon POM building blocks and look ahead to possible
      emerging application areas.

PMID- 20131347
TI  - Photochromic supramolecular memory with nondestructive readout.

PMID- 20131349
TI  - Cancer therapy with antibodies and immunoconjugates. Proceedings of the 12th
      Conference on Cancer Therapy With Antibodies and Immunoconjugates. Parsippany,
      New Jersey, USA. October 16-18, 2008.

PMID- 20131350
TI  - Nurses provide valuable proxy assessment of the health-related quality of life of
      children with Hodgkin disease.
AB  - BACKGROUND: We prospectively compared the proxy reporting of health-related
      quality of life (HRQL) by parents and nurses of children with Hodgkin disease to
      see how well they correlated with the children's report. METHODS: Children with
      all stages of Hodgkin disease, their parents, and the clinic nurse were all asked
      to complete 4 different HRQL measures at 4 time points: 2 weeks after the first
      course of chemotherapy, on the third day of the second course of chemotherapy,
      during the third week of radiation, and 1 year after diagnosis. RESULTS: Fifty
      one patients from 12 centers across Canada were enrolled in the study between May
      1, 2002 and March 31, 2005. Two patients were excluded. The children's Pediatric
      Quality of Life Inventory (PedsQL) generic scores increased from 64 at base line
      to 81 at the end of the study. There was substantial agreement (intraclass
      correlation coefficient >0.6) among the participants' scores at most time points
      except when the child was actively receiving inpatient chemotherapy. At that
      time, there was only fair to moderate agreement between the child and parent,
      with the parents on average rating the PedsQL generic score 5 points lower than
      the child. The nurses still had substantial agreement at that time point with the
      PedsQL generic and cancer module as well as the EuroQol EQ-5D visual analogue
      scale visual analogue scale. CONCLUSIONS: Over the course of treatment for
      Hodgkin disease, there was substantial agreement among the parent's, nurse's, and
      children's reported HRQL scores. Nurses contribute valuable additional
      information as proxy respondents.

PMID- 20131351
TI  - Immunohistochemical surrogate markers of breast cancer molecular classes predicts
      response to neoadjuvant chemotherapy: a single institutional experience with 359
      cases.
AB  - BACKGROUND: Complete pathologic response to neoadjuvant chemotherapy (NACT) is
      predominantly seen in "ERBB2" and "basal-like" tumors using expression profiling.
      We hypothesize that a similar response could be predicted using semiquantitative
      immunohistochemistry for estrogen receptors (ER), progesterone receptors (PR),
      and human epidermal growth factor receptor 2 (HER2). METHODS: ER, PR, and HER2
      were used to classify 359 tumors treated with NACT into 6 groups: luminal A
      (strong ER+, HER2 negative), luminal B (weak to moderate ER+, HER2 negative),
      triple negative (negative for ER, PR, and HER2), ERBB2 (negative for ER and PR,
      but HER2+), luminal A-HER2 hybrid (strong ER+ and HER2+), and luminal B-HER2
      hybrid (weak to moderate ER+ and HER2+). Complete pathologic response was defined
      as absence of invasive carcinoma in the breast and regional lymph nodes. RESULTS:
      Thirteen percent (48 of 359) demonstrated complete pathologic response. The
      highest rate of complete pathologic response was seen in ERBB2 (33%; 19 of 57)
      and triple negative (30%; 24 of 79) tumor classes. Among the ER+ "molecular"
      group, the highest rate of complete pathologic response was seen among luminal B
      HER2 hybrid tumors, 8% (2 of 24). Remainder of ER+ tumors demonstrated a very low
      rate of complete pathologic response, 1.5% (3 of 198). The 5-year survival for
      patients achieving complete pathologic response was 96% compared with 75% in
      patients that failed to achieve complete pathologic response. The overall
      survival was worse in the ER-negative group (ERBB2 and triple negative) compared
      with the ER-positive group. CONCLUSIONS: We confirm the recently defined "triple
      negative paradox," or rather "hormone receptor negative paradox," that despite
      the best response to NACT, ERBB2 and triple negative tumors show the worst
      overall survival because of higher relapse among those with residual disease.

PMID- 20131352
TI  - The relationship of the birth date of rat sympathetic neurons to the target they
      innervate.
AB  - In many parts of the nervous system, neurons with the same function often have
      similar "birth dates" (the time their precursor withdrew from the cell cycle). We
      investigated the birth dates of eight functional classes of rat sympathetic
      postganglionic neurons by injecting bromodeoxyuridine during embryonic
      development, while retrograde tracing and immunohistochemistry were used to
      identify postganglionic neurons of different functional classes in the mature
      animals. The times of withdrawal from the cell cycle overlapped, but there were
      significant differences in the peak time of withdrawal for most of the classes.
      Furthermore, sympathetic cholinergic postganglionic neurons had a significantly
      greater proportion of their total population labelled with bromodeoxyuridine than
      did any of the noradrenergic classes of neurons, indicating prenatal class
      specific differences in the handling of bromodeoxyuridine. Together, our findings
      indicate that, prior to extending axons to their targets, different functional
      classes of sympathetic neurons show differences in phenotype.

PMID- 20131353
TI  - SAR and pharmacophore models for the rhodanine inhibitors of Plasmodium
      falciparum enoyl-acyl carrier protein reductase.
AB  - Significance of type II fatty acid synthase pathway in the life cycle of malarial
      parasite has long been established. Enoyl acyl carrier protein (ACP) reductase of
      Plasmodium falciparum (PfENR) is the rate determining enzyme of its elongation
      module. Hence, PfENR has been a target for the development of antimalarials as
      well as vaccines. Towards this endeavour, we had recently identified rhodanine
      class of compounds as inhibitors of PfENR. Here, we report a number of new
      inhibitors belonging to this class. These inhibitors have been divided into two
      broad subclasses: rhodanine-furans and rhodanine-phenyls. The inhibitory activity
      of all compounds was determined against purified PfENR. IC(50) of these compounds
      were found to be in nanomolar to low-micromolar range. The structure-activity
      relationship of both the classes has been explored in detail for the first time.
      Separate 3D pharmacophore models for this enzyme have been generated for both
      rhodanine furans and phenyls. The pharmacophore model for rhodanine furan has a
      Hydrogen bond donor, two Hydrogen bond acceptors, two metal ligators, three
      hydrophobic, and two aromatic ring features, whereas the pharmacophore model for
      the phenyl subclass has two hydrogen bond donors, two hydrogen bond acceptor, a
      metal ligator, two hydrophobic, and two aromatic ring features. These models
      could be used for in silico screening of compound libraries for PfENR inhibitors.

PMID- 20131354
TI  - Loss of transcription factor AP-2gamma/TFAP2C impairs branching morphogenesis of
      the murine mammary gland.
AB  - Extensive development of the mammary gland occurs during puberty, when rising
      levels of ovarian hormones induce the formation of highly proliferative terminal
      end buds (TEBs) at the tips of mammary ducts. TEBs consist of an outer layer of
      cap cells and of inner body cells. TEBs invade the adipose stroma and bifurcate
      while extending the ducts to generate an arborized ductal network. We show that
      in murine mammary glands transcription factor AP-2gamma is strongly expressed in
      the cap cell layer and in a subset of body cells of TEBs. To decipher AP-2gamma
      functions during mammary development we generated AP-2gamma-deficient mice. Their
      mammary glands displayed impaired ductal branching and elongation. Cellular
      proliferation within TEBs was reduced. Although estrogen receptor was expressed,
      exogenously administered ovarian hormones could not restore normal development.
      Therefore, AP-2gamma is functionally involved in branching morphogenesis of the
      mammary epithelium, possibly by controlling genetic processes downstream of
      ovarian hormones.

PMID- 20131355
TI  - Expression patterns of FGF receptors in the developing mammalian cochlea.
AB  - Many studies have shown the importance of the fibroblast growth factor (FGF)
      family of factors in the development of the mammalian cochlea. There are four
      fibroblast growth factor receptors (FGFR1-4) and all four are expressed in the
      cochlea during development. While there are examples in the literature of
      expression patterns of some of the receptors at specific stages of cochlear
      development there has been no systematic study. We have assembled a full analysis
      of the patterns of receptor expression during cochlear development for all four
      Fgfrs using in situ hybridization. We have analyzed the expression patterns from
      embryonic day 13.5 through postnatal ages. We find that Fgfr1, 2, and 3 are
      expressed in the epithelium of the cochlear duct and Fgfr4 is limited in its
      expression to the mesenchyme surrounding the duct. We compare the receptor
      expression pattern to markers of the sensory domain (p27kip1) and the early hair
      cells (math1).

PMID- 20131356
TI  - Signal transduction pathways that function in both development and innate
      immunity.
AB  - C. elegans is developing in importance as a model for innate immunity. Several
      signaling pathways are known to be required for immune responses to a diverse
      range of pathogens, including the insulin signaling, p38 MAP kinase and
      transforming growth factor-beta pathways. These pathways also have roles during
      development, which can complicate the analysis of their functions in immunity.
      Recent studies have suggested that immunity in C. elegans is integrated across
      the organism by both paracrine and neuronal communication, showing the complexity
      of the immune system in this organism.

PMID- 20131357
TI  - Life span, reproductive output, and reproductive opportunity in captive Goeldi's
      monkeys (Callimico goeldii).
AB  - In the absence of long-term field studies, demographic and reproductive records
      from animals housed in zoos and research laboratories are a valuable tool for the
      study of life history variables relating to reproduction. In this study, we
      analyzed studbook records of more than 2,000 individuals born over a 40-year
      period (1965-2004) to describe life history patterns of captive Goeldi's monkeys
      (Callimico goeldii) housed in North America and Europe. Using Kaplan-Meier
      survival analysis methods, we found the mean life span to be 5.5 years. The rate
      of infant mortality, defined as death before 30 days, was approximately 30%, with
      European animals being more likely to survive infancy than North American
      animals. When individuals surviving at least 1.5 years are considered, lifetime
      reproductive output averaged 3.5 offspring, yet more than one-third of
      individuals did not produce any offspring. Using a smaller dataset of individuals
      with known pairing histories, we developed a measure of opportunity for
      reproduction (OFR), which represented the total time an individual was known to
      be housed with a potential mate. For both sexes, we found that the correlation
      between OFR and number of offspring produced was much higher than the correlation
      between life span and number of offspring produced. This result highlights the
      importance of taking into account an individual's OFR. As a whole, our findings
      help characterize the life histories of captive Goeldi's monkeys and emphasize
      the impact management practices may have on reproductive success.

PMID- 20131358
TI  - Validation of multi-detector computed tomography as a non-invasive method for
      measuring ovarian volume in macaques (Macaca fascicularis).
AB  - The purpose of this study was to validate low radiation dose, contrast-enhanced,
      multi-detector computed tomography (MDCT) as a non-invasive method for measuring
      ovarian volume in macaques. Computed tomography scans of four known-volume
      phantoms and nine mature female cynomolgus macaques were acquired using a
      previously described, low radiation dose scanning protocol, intravenous contrast
      enhancement, and a 32-slice MDCT scanner. Immediately following MDCT, ovaries
      were surgically removed and the ovarian weights were measured. The ovarian
      volumes were determined using water displacement. A veterinary radiologist who
      was unaware of actual volumes measured ovarian CT volumes three times, using a
      laptop computer, pen display tablet, hand-traced regions of interest, and free
      image analysis software. A statistician selected and performed all tests
      comparing the actual and CT data. Ovaries were successfully located in all MDCT
      scans. The iliac arteries and veins, uterus, fallopian tubes, cervix, ureters,
      urinary bladder, rectum, and colon were also consistently visualized. Large
      antral follicles were detected in six ovaries. Phantom mean CT volume was 0.702+/
      SD 0.504 cc and the mean actual volume was 0.743+/-SD 0.526 cc. Ovary mean CT
      volume was 0.258+/-SD 0.159 cc and mean water displacement volume was 0.257+/-SD
      0.145 cc. For phantoms, the mean coefficient of variation for CT volumes was
      2.5%. For ovaries, the least squares mean coefficient of variation for CT volumes
      was 5.4%. The ovarian CT volume was significantly associated with actual ovarian
      volume (ICC coefficient 0.79, regression coefficient 0.5, P=0.0006) and the
      actual ovarian weight (ICC coefficient 0.62, regression coefficient 0.6,
      P=0.015). There was no association between the CT volume accuracy and mean
      ovarian CT density (degree of intravenous contrast enhancement), and there was no
      proportional or fixed bias in the CT volume measurements. Findings from this
      study indicate that MDCT is a valid non-invasive technique for measuring the
      ovarian volume in macaques.

PMID- 20131360
TI  - An assessment of sinonasal anatomic variants potentially associated with
      recurrent acute rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: To examine sinonasal anatomic variants that may predispose
      toward recurrent acute rhinosinusitis (RARS). STUDY DESIGN: Retrospective case
      control. METHODS: Sinus computed tomography (CT) scans from a consecutive series
      of adult patients meeting strict diagnostic criteria for RARS were
      retrospectively reviewed. A control group was assembled from patients who
      underwent pituitary or temporal bone CT for a nonrhinosinusitis indication. CT
      scans were scored for the presence of Haller cells, concha bullosa, and impinging
      septal spurs. Maximal septal deviation (degrees), infundibular widths, and Lund
      staging were also assessed. The prevalence of these anatomic variants was
      statistically compared between the RARS and control groups. RESULTS: Thirty-six
      patients met diagnostic criteria for RARS (mean age, 47.2 years; 2:1 female
      preponderance); 42 control patients were identified. The mean Lund score for
      patients with RARS was 2.25 versus 1.27 for the control group (P < .001).
      Although RARS patients were more likely to manifest concha bullosa (41.7% vs.
      28.6%) or impinging septal spurs (27.8% vs. 19.0%), these differences were not
      statistically significant (P = .165 and P = .260, respectively). However,
      patients with RARS were significantly more likely to radiographically demonstrate
      Haller cells (39.9% vs. 11.9%, respectively, P = .006). Finally, patients with
      RARS had significantly smaller mean infundibular widths when compared with
      control patients (0.591 mm vs. 0.823 mm, respectively, P < .001). CONCLUSIONS:
      The presence of Haller cells and smaller infundibular widths were statistically
      associated with RARS when compared to control patients. Our data suggest that
      anatomy could play a role in the pathogenesis of RARS. Further prospective study
      is warranted.

PMID- 20131361
TI  - Evaluating the safety of frontal sinus trephination.
AB  - OBJECTIVES/HYPOTHESIS: The depth of the frontal sinus was measured using axial
      computed tomography (CT) images to examine the safety of frontal sinus
      trephination at selected distances from the midline. STUDY DESIGN: Review of 200
      sinus CT scans. METHODS: Two hundred sinus CT scans (400 frontal sinuses) were
      reviewed to measure the frontal sinus depth at 5 mm, 10 mm, and 15 mm from
      midline. RESULTS: Males had a significantly deeper frontal sinus than females at
      all measurements points (P < .001). The measurements revealed a considerable
      number of small but nonhypoplastic frontal sinuses, which were shallower than the
      length of standard frontal trephine instruments (7 mm) and would risk penetration
      of the posterior table of the sinus. Of all frontal sinuses studied, 9.54% were
      <7 mm deep at 5 mm from the midline, 10.12% at 10 mm, and 8.96% at 15 mm from the
      midline. Overall, 15.3% of all frontal sinuses studied had at least one point
      where the measured depth was <7 mm. CONCLUSIONS: Although the majority of
      patients have frontal sinuses deep enough to accommodate standard trephine
      instruments, surgeons should recognize that up to 15% of nonhypoplastic frontal
      sinuses may not be sufficiently deep at a given point to allow safe trephination
      without risking unintentional transgression of the posterior table. This study
      suggests that trephination routinely carried out at a given predetermined
      distance from the midline may be an unsafe practice. Careful evaluation of the
      imaging is essential in every case to avoid inadvertent injury and to help select
      the safest distance from the midline for frontal sinus trephination.

PMID- 20131362
TI  - Neighbor effects in marmosets: social contagion of agonism and affiliation in
      captive Callithrix jacchus.
AB  - Researchers have demonstrated the neighbor effect for affiliative and agonistic
      neighbor vocalizations in captive chimpanzees. We extend the investigation of the
      neighbor effect to New World monkeys, Callithrix jacchus. We collected data on
      vocalizations and behaviors of 31 focal individuals and concurrent neighbor
      vocalization within three behavioral categories: intragroup and intergroup
      aggression and intragroup affiliation. We investigated whether there was an
      influence of neighbor vocalizations on focal behavior within the same behavioral
      category. For data analysis we used approximate randomization of paired-sample t
      tests. We found that marmosets performed intergroup aggressive behavior (bristle,
      anogenital present for neighbor loud shrill only) for significantly longer, and
      emitted significantly more intergroup agonistic vocalizations (twitter, loud
      shrill), at a high frequency of intergroup agonistic neighbor vocalizations
      (twitter, loud shrill) than at low. The marmosets were also significantly more
      likely to engage in bristle behavior immediately after hearing a neighbor
      intergroup aggressive call (twitter, loud shrill) than directly beforehand. High
      neighbor intragroup agonistic calls (chatter) were associated with significantly
      longer spent in related behavior (composite of: attack, chase, steal food).
      Affiliative behaviors (share food, grooming invite) were engaged in by marmosets
      for significantly longer at higher frequencies of affiliative neighbor chirp
      calls than at low. Marmosets were also significantly more likely to perform food
      sharing and active affiliative contact immediately after rather than before
      hearing a neighbor chirp call. Our findings suggest that neighbor vocalizations
      influence marmoset behavior through social contagion and indicate that the
      neighbor effect for affiliation and aggression generalizes to the marmoset.

PMID- 20131363
TI  - Bone-anchored hearing aid subjective benefit for unilateral deafness.
AB  - OBJECTIVES/HYPOTHESIS: Determine the benefit of the bone-anchored hearing aid
      (BAHA) in patients with unilateral deafness. STUDY DESIGN: Retrospective case
      series and prospective questionnaire study at a tertiary referral center.
      METHODS: Patients with unilateral deafness of various etiologies who were
      implanted with a BAHA (n = 126) or not implanted with a BAHA after a
      translabyrinthine craniotomy (n = 126) were mailed questionnaires. A total of 139
      patients (55%) responded to the questionnaires. Patients who were implanted with
      a BAHA received a general questionnaire concerning BAHA usage, the Abbreviated
      Profile of Hearing Aid Benefit (APHAB), and the Speech, Spatial, and Qualities of
      Hearing Questionnaire (SSQ). Patients not implanted with a BAHA received only the
      SSQ hearing questionnaire. RESULTS: Patients with unilateral deafness
      demonstrated a benefit with BAHA use on the APHAB. Most improvement with the BAHA
      was seen in the Background Noise subscale, with a 17.4% improvement. Ease of
      Communication and Reverberation subscales also demonstrated an 11.6% and 13.2%
      benefit, respectively. Patients with a BAHA demonstrated better scores in the SSQ
      Speech subscale when compared to unilaterally deaf patients who did not have a
      BAHA, although this difference was not significant. CONCLUSIONS: The APHAB
      demonstrated significant benefit with the use of a BAHA in patients with
      unilateral deafness. Although the SSQ speech subscale showed overall improvement
      in auditory disability with the use of a BAHA, this difference was not
      significant. However, the SSQ hearing questionnaire demonstrated specific
      situations were the BAHA is most useful.

PMID- 20131364
TI  - Tonsillectomy in post-transplant lymphoproliferative disease in children.
AB  - OBJECTIVES/HYPOTHESIS: To review the role of tonsillectomy in diagnosis and
      management of post-transplant lymphoproliferative disorder (PTLD). STUDY DESIGN:
      Case series using a retrospective chart review. METHODS: A retrospective review
      of post-transplant lymphoproliferative disease at a tertiary academic medical
      center from January 2004 to April 2008. Data extracted includes patients' gender,
      age at transplantation, year of transplantation and tonsillectomy, type of
      transplant, presenting symptoms, type of immunosuppression, and outcome. RESULTS:
      Six out of 25 (24%) patients who underwent tonsillectomy were found to have PTLD.
      The patient's characteristics, gender, age at transplantation, year of
      transplantation and tonsillectomy, type of transplant, presenting symptoms, type
      of immunosuppression, and outcomes are discussed. CONCLUSIONS: In our series,
      tonsillar hypertrophy, male gender, young age at transplantation, and liver
      transplantation were associated with higher rates of PTLD. Given the devastating
      nature of PTLD, early detection with tonsillectomy and institution of treatment
      is critical.

PMID- 20131365
TI  - Characterization of mesenchymal stem cells from human vocal fold fibroblasts.
AB  - OBJECTIVES/HYPOTHESIS: Mesenchymal stem cells (MSCs) originally isolated from
      bone marrow (BM), are fibroblast-looking cells that are now assumed to be present
      in the stromal component of many tissues. MSCs are characterized by a certain set
      of criteria, including their growth culture characteristics, a combination of
      cell surface markers, and the ability to differentiate along multiple mesenchymal
      tissue lineages. We hypothesized that human vocal fold fibroblasts (hVFF)
      isolated from the lamina propria meet the criteria established to define MSCs and
      are functionally similar to MSCs derived from BM and adipose tissue. STUDY
      DESIGN: In vitro study. METHODS: hVFF were previously derived from human vocal
      fold tissues. MSCs were derived from adipose tissue (AT), and BM of healthy
      donors based on their attachment to culture dishes and their morphology and
      expanded in culture. Cells were analyzed for standard cell surface markers
      identified on BM-derived MSCs and the ability to differentiate into cells of
      mesenchymal lineage (i.e., fat, bone, and cartilage). We investigated the
      immunophenotype of these cells before and after interferon-gamma (INF-gamma)
      stimulation. RESULTS: hVFF displayed cell surface markers and multipotent
      differentiation capacity characteristic of MSCs. Furthermore, these cells
      exhibited similar patterns of expression of human leukocyte antigen and
      costimulatory molecules, after stimulation with INF-gamma compared to MSCs
      derived from BM and AT. CONCLUSIONS: Based on our findings, hVFF derived from
      lamina propria have the same cell surface markers, immunophenotypic
      characteristics, and differentiation potential as BM- and AT-derived MSCs. We
      propose that vocal fold fibroblasts are MSCs resident in the vocal fold lamina
      propria.

PMID- 20131366
TI  - Outcomes of static and dynamic facial nerve repair in head and neck cancer.
AB  - OBJECTIVES/HYPOTHESIS: Determine outcomes associated with nerve grafting versus
      static repair following facial nerve resection. STUDY DESIGN: Retrospective chart
      review. METHODS: Charts from 105 patients who underwent facial nerve
      reconstruction between January 1999 and January 2009 were reviewed. The majority
      had parotid malignancy (78.1%), most commonly squamous cell carcinoma (50.5%).
      Patients underwent static (n = 72) or dynamic (n = 33) reconstruction with nerve
      grafting. Facial nerve function was measured using the House-Brackmann (H-B)
      scale. RESULTS: Patients receiving static reconstruction were on average 10.3
      years older (P = .002). Mean overall survival for tumor cases was 61.9 months;
      parotid squamous cell carcinoma was associated with worse prognosis (P = .10).
      Median follow-up was 16.1 months (range, 4-96.1 months). Most (97%) patients
      receiving a nerve graft had some return of function at a median of 6.2 months
      postoperatively (range, 4-9 months) and the majority (63.6%) had good function (H
      B score <or=4). Patients having static reconstruction (29.2%) were more likely to
      have symptomatic facial palsy than those having a nerve graft (15.2%, P = .12).
      CONCLUSIONS: Where possible, nerve grafting is the preferred method of facial
      nerve reconstruction. Although elderly patients with parotid malignancy have
      traditionally been considered poor candidates for nerve grafting, we demonstrate
      good results within 9 months of facial nerve repair even with radiotherapy, the
      use of long grafts (>6 cm), and prolonged preoperative dysfunction.

PMID- 20131367
TI  - Gorham-Stout disease of the temporal bone.
AB  - Gorham-Stout (GS) disease is a rare disease of the bone and is also known as
      massive osteolysis. Less than 200 cases have been reported in the world
      literature. A 29-year-old female with a diagnosis of GS disease was identified.
      She complained of aural fullness and tinnitus bilaterally. Demineralization and
      moth-eaten changes of the osseous structures of the skull base and posterior
      fossa were prominent. The left mastoid air cells were opacified and erosion
      extended to the left jugular foramen, left hypoglossal canal, left stylomastoid
      process, and left eustachian tube. The radiographic findings and brief literature
      review are presented.

PMID- 20131368
TI  - Analysis of hearing preservation after endolymphatic mastoid sac surgery for
      Meniere's disease.
AB  - OBJECTIVES/HYPOTHESIS: Comparison of audiometric outcomes between patients with
      definite Meniere's disease who underwent endolymphatic mastoid sac surgery (EMSS)
      following failed medical therapy and patients who underwent medical therapy only.
      STUDY DESIGN: Retrospective chart review of 456 consecutive patients between 1997
      and 2006. METHODS: Outcome measures were changes in pure-tone average (PTA), word
      recognition score (WRS), and speech reception threshold (SRT). RESULTS: Of 58
      qualified patients, 29 who underwent EMSS after failing medical therapy showed a
      4 dB decrease in PTA, a 2% increase in WRS, and a 2 dB decrease in SRT. Twenty
      nine patients treated with medical therapy only demonstrated a 1 dB PTA increase,
      2% WRS improvement, and 2 dB SRT improvement. No significant difference was noted
      between the medically and surgically managed patients in terms of changes in PTA
      (P = .34) or WRS (P = .95) after treatment. Of all patients in the study, 60% had
      no clinically significant change in hearing, whereas 24% improved and 16%
      worsened. The distribution of post-treatment hearing changes between the medical
      and surgical groups was statistically insignificant (P = .17). CONCLUSIONS: The
      changes in PTA and WRS among patients with Meniere's disease managed with medical
      therapy or EMSS were not statistically significant. Although performing EMSS to
      treat the vertigo of Meniere's disease does not appear to be associated with an
      increased risk of deteriorating auditory function after treatment, surgery also
      does not confer an increased likelihood of stabilizing or improving hearing.

PMID- 20131369
TI  - Hypopharyngeal pharyngoplasty for the management of piriform fossa sinus.

PMID- 20131370
TI  - Tissue regeneration of the vocal fold using bone marrow mesenchymal stem cells
      and synthetic extracellular matrix injections in rats.
AB  - OBJECTIVES/HYPOTHESIS: To determine the effectiveness of bone marrow mesenchymal
      stem cell (BM-MSC) transplantation in isolation or within a synthetic
      extracellular matrix (sECM) for tissue regeneration of the scarred vocal fold
      lamina propria. METHODS: In vitro stability and compatibility of mouse BM-MSC
      embedded in sECM was assessed by flow cytometry detection of BM-MSC marker
      expression and proliferation. Eighteen rats were subjected to vocal fold injury
      bilaterally, followed by 1 month post-treatment with unilateral injections of
      saline or sECM hydrogel (Extracel; Glycosan BioSystems, Inc., Salt Lake City,
      UT), green fluorescence protein (GFP)-mouse BM-MSC, or BM-MSC suspended in sECM.
      Outcomes measured 1 month after treatment included procollagen-III, fibronectin,
      hyaluronan synthase-III (HAS3), hyaluronidase (HYAL3), smooth muscle actin (SMA),
      and transforming growth factor-beta 1(TGF-beta1) mRNA expression. The persistence
      of GFP BM-MSC, proliferation, apoptosis, and myofibroblast differentiation was
      assessed by immunofluorescence. RESULTS: BM-MSC grown in vitro within sECM
      express Sca-1, are positive for hyaluronan receptor CD44, and continue to
      proliferate. In the in vivo study, groups injected with BM-MSC had detectable GFP
      labeled BM-MSC remaining and showed proliferation and low apoptotic or
      myofibroblast markers compared to the contralateral side. Embedded BM-MSC in the
      sECM group exhibited increased levels of procollagen III, fibronectin, and TGF
      beta1. BM-MSC within sECM downregulated the expression of SMA compared to BM-MSC
      alone and exhibited upregulation of HYAL3 and no change in HAS3 compared to
      saline. CONCLUSIONS: Treatment of vocal fold scarring with BM-MSC injected in a
      sECM displayed the most favorable outcomes in ECM production, hyaluronan
      metabolism, myofibroblast differentiation, and production of TGF-beta1.
      Furthermore, the combined treatment had no detectable cytotoxicity and preserved
      local cell proliferation.

PMID- 20131371
TI  - The effect of AlloDerm on the initiation and growth of human neovessels.
AB  - OBJECTIVES/HYPOTHESIS: AlloDerm (LifeCell Corp., Branchburg, NJ) is commonly
      employed for reconstruction of ablative soft tissue and mucosal defects following
      surgical resections. Although devoid of growth factors, AlloDerm may serve as an
      adhesive matrix for binding of growth factors, increasing local angiogenesis, and
      wound healing. We hypothesized that AlloDerm would enhance angiogenesis and might
      be altered with autologous blood products to enhance initiation of the angiogenic
      response. METHODS: We used a human placental vein in a fibrin-thrombin clot-based
      angiogenesis model. Four groups, human placental vein (HPVM), HPVM with AlloDerm,
      HPVM with AlloDerm plus platelet-poor plasma, and HPVM with AlloDerm plus
      platelet-rich plasma were evaluated. Endothelial cell growth was evaluated
      visually (40x). Hematoxylin and eosin staining and immunofluorescent staining for
      growth within the AlloDerm matrix were also performed. To assess human umbilical
      vein endothelial cell (HUVEC) sites of attachment to AlloDerm, we incubated HUVEC
      cells with AlloDerm for a period of 2 weeks and evaluated attachment with anti
      factor VIII immunofluorescence. RESULTS: Angiogenic initiation decreased in the
      combined placental vein with AlloDerm group (P < .0001 at day 7, 14, 21).
      Additionally, initiation in the AlloDerm plus platelet-poor plasma group was
      significantly better than the AlloDerm alone group when placentas 2 and 3 were
      compared (P < .0001). On hematoxylin and eosin staining and immunofluorescent
      factor VIII staining, no endothelial growth into the AlloDerm was noted in the
      samples analyzed. CONCLUSIONS: AlloDerm may be enriched with platelet-poor plasma
      to stimulate greater initiation and wound healing; however, AlloDerm inhibits
      angiogenic initiation in this model.

PMID- 20131374
TI  - Prevalence and cost of medication nonadherence in Parkinson's disease: evidence
      from administrative claims data.
AB  - We estimated the prevalence of medication nonadherence in Parkinson's disease
      (PD) and the association between treatment nonadherence and healthcare costs.
      Insurance claims from over 30 US health plans were analyzed. Inclusion criteria
      were as follows: PD diagnosis, >or=1 PD-related prescription between 1/1/1997 and
      12/31/2004, continuous health plan enrollment for >or=6 months before and >or=12
      months after first PD prescription. Adherence, all-cause healthcare utilization,
      and all-cause costs were evaluated over 12 months post-treatment initiation.
      Adherence was measured using the medication possession ratio (MPR), with MPR <
      0.8 defining nonadherence. Among patients identified for inclusion (N = 3,119),
      58% were male and mean age was 69 years. Mean MPR was 0.58 and 61% of patients
      were nonadherent. Unadjusted mean medical costs were significantly higher (P <
      0.01) among nonadherers ($15,826) compared with adherers ($9,228), although
      nonadherers had lower prescription drug costs ($2,684 vs. $3,854; P < 0.05).
      After controlling for confounders in multivariable analyses, a large positive
      relationship between nonadherence and both medical and total healthcare costs
      remained (+$3,451, P < 0.0001 and +$2,383, P = 0.0053, respectively). Medication
      adherence in PD is suboptimal and nonadherence may be associated with increased
      healthcare costs despite offsets from reduced drug intake. Efforts to promote
      medication adherence in PD may lead to cost savings for managed care systems.

PMID- 20131372
TI  - Impact of belief in neuroprotection on therapeutic intervention in Parkinson's
      disease.
AB  - We explored the hypotheses that an investigator's belief in a putative
      neuroprotective agent might influence the timing of symptomatic intervention and
      the assessment of signs and symptoms of patients with Parkinson's disease with
      the Unified Parkinson's Disease Rating Scale (UPDRS). These hypotheses were
      tested with Cox and general linear modeling, using data from a previously
      published double-blind placebo-controlled futility trial of coenzyme Q(10) and
      GPI-1485. We found the investigators' level of confidence in these agents had no
      effect on the time to symptomatic therapy or on the change in UPDRS during 12
      months of treatment.

PMID- 20131375
TI  - Correlation of (2)J couplings with protein secondary structure.
AB  - Geminal two-bond couplings ((2)J) in proteins were analyzed in terms of
      correlation with protein secondary structure. NMR coupling constants measured and
      evaluated for a total six proteins comprise 3999 values of (2)J(CalphaN'),
      (2)J(C'HN), (2)J(HNCalpha), (2)J(C'Calpha), (2)J(HalphaC'), (2)J(HalphaCalpha),
      (2)J(CbetaC'), (2)J(N'Halpha), (2)J(N'Cbeta), and (2)J(N'C'), encompassing an
      aggregate 969 amino-acid residues. A seamless chain of pattern comparisons across
      the spectrum datasets recorded allowed the absolute signs of all (2)J coupling
      constants studied to be retrieved. Grouped by their mediating nucleus, C', N' or
      C(alpha), (2)J couplings related to C' and N' depend significantly on phi,psi
      torsion-angle combinations. beta turn types I, I', II and II', especially, can be
      distinguished on the basis of relative-value patterns of (2)J(CalphaN'),
      (2)J(HNCalpha), (2)J(C'HN), and (2)J(HalphaC'). These coupling types also depend
      on planar or tetrahedral bond angles, whereas such dependences seem insignificant
      for other types. (2)J(HalphaCbeta) appears to depend on amino-acid type only,
      showing negligible correlation with torsion-angle geometry. Owing to its unusual
      properties, (2)J(CalphaN') can be considered a "one-bond" rather than two-bond
      interaction, the allylic analog of (1)J(N'Calpha), as it were. Of all protein J
      coupling types, (2)J(CalphaN') exhibits the strongest dependence on molecular
      conformation, and among the (2)J types, (2)J(HNCalpha) comes second in terms of
      significance, yet was hitherto barely attended to in protein structure work.

PMID- 20131376
TI  - Feature space resampling for protein conformational search.
AB  - De novo protein structure prediction requires location of the lowest energy state
      of the polypeptide chain among a vast set of possible conformations. Powerful
      approaches include conformational space annealing, in which search progressively
      focuses on the most promising regions of conformational space, and genetic
      algorithms, in which features of the best conformations thus far identified are
      recombined. We describe a new approach that combines the strengths of these two
      approaches. Protein conformations are projected onto a discrete feature space
      which includes backbone torsion angles, secondary structure, and beta pairings.
      For each of these there is one "native" value: the one found in the native
      structure. We begin with a large number of conformations generated in independent
      Monte Carlo structure prediction trajectories from Rosetta. Native values for
      each feature are predicted from the frequencies of feature value occurrences and
      the energy distribution in conformations containing them. A second round of
      structure prediction trajectories are then guided by the predicted native feature
      distributions. We show that native features can be predicted at much higher than
      background rates, and that using the predicted feature distributions improves
      structure prediction in a benchmark of 28 proteins. The advantages of our
      approach are that features from many different input structures can be combined
      simultaneously without producing atomic clashes or otherwise physically inviable
      models, and that the features being recombined have a relatively high chance of
      being correct.

PMID- 20131378
TI  - NMR structure of a phosphatidyl-ethanolamine binding protein from Drosophila.

PMID- 20131379
TI  - Male reproductive and behavior toxicity in rats after subchronic exposure to
      organic extracts from Jialing River of Chongqing, China.
AB  - BACKGROUND: More than 100 species of organic chemicals have been detected in
      Jialing River of Chongqing City. Most of them are endocrine-disrupting chemicals
      (EDCs), which can disrupt the functions of the reproductive and nervous systems.
      METHODS: Organic extracts (OE) were obtained by solid extraction from the Jialing
      River, and administrated to rats by gavage every other day for 13 weeks at doses
      of 2, 12, and 72 L/kg bw/d. Sperm abnormity was analyzed by microscopy and flow
      cytometry. The Morris water maze task was employed to investigate the behaviors
      of space probing. Activities of superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) and malondialdehyde (MDA) content were measured to detect the
      peroxidation response in hippocampus and testis. RESULTS: Animals in the 72-L/kg
      group showed significant degeneration of germ cells in the seminiferous tubule.
      Sperm abnormality of the 72-L/kg group was significantly higher than that of the
      solvent control group. The testis oxidative stress in the 72-L/kg group was
      severer than that of the other groups. The hippocampus neuron cells in the 72
      L/kg group showed cellular edema and remarkable cell enlargement. The hippocampus
      oxidative stress in the 72-L/kg group was severer and the Morris water maze
      performance in this group showed longer latency time and swimming distance in the
      probing platform than the other groups. CONCLUSIONS: OE caused pathological
      damage and peroxidation response to testis and hippocampus and disrupted
      spermatogenesis and behavior of space probing.

PMID- 20131380
TI  - Maternal cypermethrin exposure during lactation impairs testicular development
      and spermatogenesis in male mouse offspring.
AB  - Within the last decade, numerous epidemiological studies have demonstrated that
      endocrine disruptors are a possible cause for a decline in semen quality.
      Cypermethrin is a widely used pyrethroid insecticide, but little is known about
      its potentially adverse effects on male reproduction. In the present study, we
      investigated the effects of maternal cypermethrin exposure during lactation on
      testicular development and spermatogenesis in male offspring. Maternal mice were
      administered with cypermethrin (25 mg/kg) by gavage daily from postnatal day 0
      (PND0) to PND21. Results showed that the weight of testes at PND21 was
      significantly decreased in pups whose mothers were exposed to cypermethrin during
      lactation. Maternal cypermethrin exposure during lactation markedly decreased the
      layers of spermatogenic cells, increased the inside diameter of seminiferous
      tubules, and disturbed the array of spermatogenic cells in testes of pups at
      PND21. In addition, maternal cypermethrin exposure during lactation markedly
      reduced mRNA and protein levels of testicular P450scc, a testosterone (T)
      synthetic enzyme. Correspondingly, the level of serum and testicular T at weaning
      was significantly decreased in pups whose mothers were exposed to cypermethrin
      during lactation. Although the expression of testicular T synthetic enzymes and
      serum and testicular T in adulthood had restored to control level, the decreased
      testicular weight and histological changes were irreversible. Importantly, the
      number of spermatozoa was significantly decreased in adult male offspring whose
      mothers were exposed to cypermethrin during lactation. In conclusion, maternal
      cypermethrin exposure during lactation permanently impairs testicular development
      and spermatogenesis in male offspring, whereas cypermethrin-induced endocrine
      disruption is reversible.

PMID- 20131381
TI  - Changes in exhaled nitric oxide after ingestion of L-arginine in children: a
      pilot study.
AB  - RATIONALE: Exhaled nitric oxide (FE(NO)) may be a useful biomarker for asthma and
      is derived from enzymatic activity on the amino acid L-arginine. The aim of the
      present pilot study was to study the effect of L-arginine ingestion on FE(NO) and
      also NO production in the proximal and distal airways. METHODS: Asthmatic and
      control children were enrolled and phenotyped by skin prick reactivity and
      spirometry. FE(NO) was measured before and after ingestion of 0.2 g/kg L
      arginine. Proximal and distal NO production (J'awNO and CANO) were derived using
      the method of Tsoukias. RESULTS: Twenty children were recruited, 11 steroid
      treated asthmatics, 1 steroid-naive asthmatic, and 8 healthy controls. The median
      baseline FE(NO) before L-arginine administration was 31 ppb (interquartile range,
      IQR, 15, 61). At baseline, the median J'awNO was 1000 nl/sec (IQR 650, 2880) and
      the median CANO was 2.3 ppb (IQR 1.8, 4.5). FE(NO) rose by an average of 5.5 ppb
      [95% CI 3.5, 7.5] (P < 0.001) 60 min after ingestion of L-arginine and 1.5 ppb
      [95% CI -0.9, 4.0] (P = 0.188) after 120 min. One hour after L-arginine
      ingestion, J'awNO did not change but CANO rose by an average of 2.6 ppb [95% CI
      0.5, 4.7], P = 0.020. CONCLUSION: The rise in FE(NO) after dietary exposure to L
      arginine is modest, transient, and of little or no clinical significance.

PMID- 20131382
TI  - Associations of tonsillar hypertrophy and snoring with history of wheezing in
      childhood.
AB  - BACKGROUND: Reports in adults and children have correlated history of wheezing or
      asthma with the presence of obstructive sleep-disordered breathing but the
      mechanism of this epidemiologic association is unknown. The goal of the present
      study was to examine whether tonsillar hypertophy can explain this association.
      METHODS: Children were recruited from the Emergency Department and the Pediatric
      Pulmonology Clinic. History of wheezing requiring treatment (explanatory
      variable) and snoring > or = 1 night/week (outcome) were recorded and presence of
      tonsillar hypertrophy (outcome) was assessed. RESULTS: Four hundred forty-two
      children were recruited (mean age: 7.6 + or - 3.6 years) and 210 of them had
      history of wheezing. History of wheezing was significantly associated with the
      presence of tonsillar hypertrophy and snoring even after adjustment for age,
      gender, obesity, and passive smoking [odds ratio (95% confidence interval): 2.23
      (1.37-3.63); P = 0.001 and 1.73 (1.12-2.67); P = 0.013, respectively]. When only
      children with tonsillar hypertrophy were considered (n = 92), history of wheezing
      was significantly related to the presence of snoring, whereas in subjects without
      tonsillar hypertrophy (n = 350) wheezing did not affect snoring [odds ratio: 2.76
      (1.10-6.93); P = 0.031 and 1.49 (0.92-2.43); P = 0.107, respectively].
      CONCLUSIONS: Children with history of wheezing have more frequently tonsillar
      hypertrophy than those without wheezing. Tonsillar hypertrophy may mediate at
      least in part the reported association between asthma and obstructive sleep
      disordered breathing in childhood.

PMID- 20131383
TI  - Cardiac sympathetic degeneration correlates with olfactory function in
      Parkinson's disease.
AB  - Autonomic and olfactory dysfunctions are considered markers for preclinical
      diagnosis in Parkinson's disease (PD), because pathological changes in these
      systems can start before motor symptoms develop. We investigated whether cardiac
      sympathetic function and olfactory function are associated in PD. Participants
      comprised 40 nondemented patients with idiopathic PD, and age-matched controls.
      Cardiac sympathetic function was evaluated by (123) I-metaiodobenzylguanidine
      (MIBG) uptake, in terms of the heart to mediastinum (H/M) ratio in both early and
      delayed images, and the washout rate (WR). Olfactory function was evaluated using
      the Odor Stick Identification Test for Japanese, which evaluates the detection of
      12 odorants familiar to Japanese participants. Smell identification scores were
      significantly lower (P < 0.001) in patients with PD than in controls. Smell
      identification scores correlated positively with early (P < 0.05) and delayed H/M
      ratios (P < 0.01), and inversely with the WR (P < 0.005) especially in patients
      with early PD (below 5 years of the start of motor symptoms), whereas smell
      identification scores did not correlate with any parameters of MIBG in the
      advanced PD (above 5 years of the start of motor symptoms). There was no
      correlation between motor symptom scores and smell identification scores, H/M
      ratios, or WR. The results suggest that the cardiac sympathetic nervous system
      might degenerate in parallel with the olfactory system in patients with early PD,
      and that these two systems might degenerate at a different rate of speed in
      advanced PD.

PMID- 20131384
TI  - Descriptions of cervical dystonia by Sir Charles Bell.
AB  - Sir Charles Bell is better known among neurologists for his descriptions of the
      clinical consequences of facial nerve lesions. However, as an accomplished
      physician, anatomist, and artist, he made many other contributions to the fields
      of neurology and neuroscience. Among those, his descriptions of patients with
      what we now know as cervical dystonia have not received much attention. In this
      report, Bell's depictions of patients presenting with a syndrome consistent with
      cervical dystonia will be discussed, including the identification of many of the
      different clinical features we currently use for the diagnosis of this disorder
      and his thoughts about its pathogenesis.

PMID- 20131385
TI  - Background scenery visual hallucinations in a depressed patient with Parkinson's
      disease.

PMID- 20131386
TI  - Four-week trunk-specific rehabilitation treatment improves lateral trunk flexion
      in Parkinson's disease.
AB  - People with Parkinson's disease (PD) often have a posture characterized by
      lateral trunk flexion poorly responsive to antiparkinsonian drugs. To examine the
      effects of a rehabilitation programme (daily individual 90-minute-sessions, 5
      days-a-week for 4-consecutive weeks) on lateral trunk flexion and mobility, 22 PD
      patients with mild to severe lateral trunk flexion, and 22 PD patients without
      trunk flexion were studied. Patients were evaluated using the Unified Parkinson's
      Disease Rating Scale motor subscale (UPDRS-III) score, and the kinematic behavior
      of the trunk was recorded by means of an optoelectronic system to determine: a)
      trunk flexion, inclination and rotation values in the erect standing posture; b)
      ranges of trunk flexion and inclination during trunk movements. After the
      treatment, significant decreases in trunk flexion [24 degrees (4) vs. 14 degrees
      (3), P < 0.001] and inclination in the static condition [23 degrees (5) vs. 12
      degrees (4), P < 0.001)] were observed, both of which were maintained at the 6
      month follow up. During the trunk flexion task, a significantly increased range
      of trunk flexion [64 degrees (15) vs. 83 degrees (15), P < 0.001] was observed;
      similarly, during the lateral bending task, the range of trunk inclination was
      found to be significantly increased, both toward the side of the trunk deviation
      [29 degrees (8) vs. 42 degrees (13), P < 0.01] and toward the contralateral side
      [14 degrees (6) vs 29 degrees (11), P < 0.01]. No further significant changes
      were observed at the 6-month follow-up. Trunk flexion and inclination values in
      the upright standing posture correlated slightly with the UPDRS-III score. Our
      findings show that significant improvements in axial posture and trunk mobility
      can be obtained through the 4-week rehabilitation programme described, with a
      parallel improvement in clinical status.

PMID- 20131387
TI  - Narcolepsy with cataplexy associated with holoprosencephaly misdiagnosed as
      epileptic drop attacks.

PMID- 20131388
TI  - Glucocerebrosidase gene L444P mutation is a risk factor for Parkinson's disease
      in Chinese population.
AB  - An association between mutations in the glucocerebrosidase (GBA) gene and
      Parkinson's disease (PD) has been reported in several populations. We searched
      for four common GBA mutations (L444P, F213I, R353W, and N370S) in 402 Chinese PD
      patients and 413 age- and sex-matched controls. In the PD cohort, 11 patients
      were found carrying a heterozygous GBA mutation and all of them had the L444P
      mutation. Heterozygous GBA mutations were detected none in controls. The GBA gene
      L444P mutation was detected at a significantly higher frequency among PD patients
      (11/402 = 2.74%), when compared with the control group (0/413): P = 0.0007. To
      evaluate the possible role of the GBA gene L444P mutation in PD in Ashkenazi
      Jewish and non-Jewish populations, we conducted a meta-analysis on the topic. In
      the Chinese population, the GBA gene L444P mutation was detected at a
      significantly higher frequency among PD patients, when compared with the control
      group: Z = 3.83, P = 0.0001, OR = 8.42, confidence interval = 95%, 2.83-25.06. In
      the non-Jewish populations, the difference was obviously significant: Z = 5.76, P
      < 0.00001, OR = 8.82, confidence interval = 95%, 4.21-18.48. The results suggest
      that the GBA gene L444P mutation appears to be a risk factor for PD in Chinese
      population.

PMID- 20131389
TI  - A case-control study on restless legs syndrome in nondialyzed patients with
      chronic renal failure.
AB  - Restless legs syndrome (RLS) is a possible consequence of end-stage renal
      disease. However, conclusive data on the association between RLS and chronic
      renal failure (CRF) in nondialyzed patients are still lacking. The aims of this
      study were: (1) to look for an association between RLS and CRF in nondialyzed
      patients; (2) to analyze the characteristics of RLS and its consequences on
      nocturnal rest in nondialyzed patients with CRF; (3) to identify possible
      predictors of RLS occurrence in nondialyzed patients with CRF. We recruited 138
      nondialyzed patients with CRF (mean age: 69.8 +/- 11.7 years; male: 61.6%) and
      151 controls (mean age: 60.2 +/- 18.6 years; male: 42.4%). An expert in sleep
      medicine investigated the presence of RLS by means of a face-to-face interview.
      Fifteen nondialyzed CRF patients and five controls were diagnosed as RLS
      affected. A multivariate analysis confirmed that RLS was independently associated
      with CRF in nondialyzed patients (P = 0.004). CRF patients RLS(+) were more
      commonly women and showed the presence of an iron deficiency compared with the
      RLS(-) ones. Independent predictors of RLS in nondialyzed CRF patients were:
      female sex (OR: 10.7, 95% CI: 2.2-31.3; P = 0.004) and percentage of transferrin
      saturation (OR: 0.6, 95% CI: 0.4-0.9; P = 0.04). This is the first case-control
      study able to recognize an association between RLS and CRF in patients not yet on
      dialysis. Nephrologists should investigate and treat RLS in their nondialyzed
      patients with CRF. In particular, physicians should carefully investigate women
      and patients with iron deficiency in the presence of RLS symptoms.

PMID- 20131390
TI  - Adult-onset dystonia in Aicardi-Goutieres syndrome.

PMID- 20131391
TI  - Excessive hoarding in Parkinson's disease.
AB  - Hoarding is seen in several psychiatric conditions, but has not been specifically
      assessed in Parkinson's disease (PD). This study investigates hoarding tendency
      amongst patients with PD, and its association with impulsive-compulsive spectrum
      behaviors (ICBs). We compare clinical features, measures of hoarding, impulse
      buying, self-control, obsessive-compulsive symptoms, depression, and anxiety in
      39 patients with PD with ICBs (PD + ICB), 61 patients with PD without ICBs (PD -
      ICB), and 50 healthy controls. A much higher proportion of PD + ICB (27.8%) than
      PD - ICB (3.5%) were hoarders (P = 0.001). 6% of healthy controls were hoarders.
      Compulsive shoppers scored higher than other varieties of ICB on excessive
      acquisition measures. Hoarding correlated positively with impulsive buying,
      obsessive-compulsive symptoms, PD duration, and negatively with self-control
      measures. Using multivariate regression analyzes, the presence of ICBs and
      measures of impulsive buying were the only variables independently associated
      with hoarding in PD. The association of hoarding with other ICBs and low trait
      impulse control suggests that excessive hoarding is related to the spectrum of
      impulsive behaviors in PD.

PMID- 20131392
TI  - Feeling-of-knowing in episodic memory in patients with Parkinson's disease with
      various motor symptoms.
AB  - The aim of this study was to examine metamemory in patients with Parkinson's
      disease (PD) with different dominant motor symptoms. This is a prospective case
      control study. Fifty-five PD patients [25 patients with tremor-dominant (TD)
      motor symptoms and 30 patients with akinetic and rigidity-dominant (ARD) motor
      symptoms] and 30 normal controls were studied. The two patient groups were
      similar in terms of age, level of education, disease duration, and disease
      severity. Metamemory was measured using the experimental metamemory task [feeling
      of-knowing (FOK) paradigm]. In addition, memory and executive functions were
      determined using detailed cognitive tests. In comparison with normal subjects and
      TD patients, ARD patients exhibited impaired FOK accuracy (P = 0.007).
      Furthermore, correlation analysis revealed an intergroup differential pattern,
      which indicated that FOK accuracy was primarily related to memory ability in ARD
      patients and executive function in TD patients. Our results provide evidence of
      impaired metamemory in the early stages of PD with ARD rather than TD motor
      symptoms. These findings might be useful for designing specific medical care
      strategies for ARD patients. Further studies are needed to determine whether
      impaired metamemory is an early predictor for brain alteration in PD patients.

PMID- 20131393
TI  - Orthostatic tremor in a left midbrain lesion.

PMID- 20131395
TI  - Higher-dose glutathione therapy for Parkinson's disease in Japan: is it really
      safe?

PMID- 20131394
TI  - Distinguishing SWEDDs patients with asymmetric resting tremor from Parkinson's
      disease: a clinical and electrophysiological study.
AB  - Approximately 10% of patients diagnosed clinically with early Parkinson's disease
      (PD) have normal dopaminergic functional imaging (Scans Without Evidence of
      Dopaminergic Deficit [SWEDDs]). An important subgroup of SWEDDs are those with
      asymmetric rest tremor resembling parkinsonian tremor. Clinical and
      pathophysiological features which could help to distinguish SWEDDs from PD have
      not been explored. We therefore studied clinical details including non-motor
      symptoms in 25 tremulous SWEDDs patients in comparison to 25 tremor-dominant PD
      patients. Blinded video rating was used to compare examination findings.
      Electrophysiological tremor parameters and also response to a cortical plasticity
      protocol using paired associative stimulation (PAS) was studied in 9 patients
      with SWEDDs, 9 with tremor-dominant PD (with abnormal dopamine transporter single
      photon emission computed tomography findings), 8 with segmental dystonia, and 8
      with essential tremor (ET). Despite clinical overlap, lack of true bradykinesia,
      presence of dystonia, and head tremor favored a diagnosis of SWEDDs, whereas re
      emergent tremor, true fatiguing or decrement, good response to dopaminergic
      drugs, and presence of non-motor symptoms favored PD. A single tremor parameter
      could not differentiate between groups, but the combination of re-emergent tremor
      and highest tremor amplitude at rest was characteristic of PD tremor. SWEDDs and
      segmental dystonia patients exhibited an abnormal exaggerated response to the PAS
      protocol, in contrast to a subnormal response in PD and a normal response in ET.
      We conclude that despite clinical overlap, there are features that can help to
      distinguish between PD and SWEDDs which may be useful in clinical practice. The
      underlying pathophysiology of SWEDDs differs from PD but has similarities with
      primary dystonia.

PMID- 20131396
TI  - Clinical and dual-tasking aspects in frequent and infrequent fallers with
      progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with no
      sufficient therapeutic options to date. Falls are the most devastating feature.
      The causes of these falls are not well understood. To test the impact of PSP
      associated motor and cognitive features on falls, 26 PSP patients were
      prospectively recruited and divided into frequent fallers (> one fall/month, 18
      patients) and infrequent fallers (<or= one fall/month, 8 patients). Further
      parameters were assessed by clinical investigation and biomechanical gait and
      balance analysis with and without dual-task paradigms. Physical activity was
      measured through an ambulatory device. Frequent fallers scored higher on the
      total PSP rating scale and the subscales "history," "mental," "bulbar,"
      "supranuclear ocular motor," and "gait/midline exam" but not on disease duration,
      the subscale "limb exam," the UPDRS motor score and the sway analysis. Frequent
      fallers also showed an increased probability of an altered walking pattern with
      shortened step lengths and increased cadence under a dual-task situation. It is
      concluded that the occurrence of falls in PSP seems strongly associated with the
      deterioration of bulbar function, but not relevantly with typical parkinsonian
      features like rigidity and bradykinesia. The decreased ability to deal with
      distraction of attention under a dual-task situation points to a relevant impact
      of cortical and subcortical dysfunction on the frequency of falls.

PMID- 20131397
TI  - Myorhythmia associated with listerial rhombencephalitis.

PMID- 20131398
TI  - Identification of B cells through negative gating-An example of the MIFlowCyt
      standard applied.
AB  - Polychromatic flow cytometric analysis takes advantage of the increasing number
      of available fluorophores to positively identify and simultaneously assess
      multiple parameters in the same cell (1). Additional parameters may be analyzed
      through negative identification (i.e., through exclusion of particular stains or
      antibodies employed). In this report, we tested whether such negative-gating
      strategy would identify human B lymphocytes in innate immune phenotyping studies.
      To this end, B cells were identified as the negatively-stained subpopulation from
      the CD123 vs. CD11c plot of the CD14(neg-low), MHC II(high) human peripheral
      blood mononuclear cells. To test the specificity of this negative gating
      approach, we confirmed that negatively gated B cells indeed expressed CD19, the
      bona fide marker for human B cells. However, a small number of unidentified cells
      were contained in the negatively-gated B cells. Furthermore, a small percentage
      cells expressing markers used to identify monocytes and myeloid dendritic cells
      (mDC) coexpressed CD19. This identifies such negative B-cell gating approach as
      potentially problematic. When applied to the analysis of Toll-like receptors
      (TLR) stimulation experiments, we were however able to interpret the results, as
      B-cells respond to TLR stimulation in a qualitative different pattern as compared
      to monocytes and DC. This report is presented in a manner that is fully compliant
      with the Minimum Information about a Flow Cytometry Experiment (MIFlowCyt)
      standard, which was recently adopted by the International Society for Advancement
      of Cytometry (ISAC) (2) and incorporated in the publishing policies of Cytometry
      and other journals. We demonstrate how a MIFlowCyt-compliant report can be
      prepared with minimal effort, and yet provide the reader with a much clearer
      picture of the portrayed FCM experiment and data.

PMID- 20131399
TI  - Levodopa-aggravated lateral flexion of the neck and trunk as a delayed phenomenon
      of unilateral pallidotomy.

PMID- 20131400
TI  - GPi-pallidal stimulation to treat generalized dystonia in Cockayne syndrome.

PMID- 20131401
TI  - Spasticity treatment facilitates direct care delivery for adults with profound
      intellectual disability.
AB  - Many adults with intellectual disabilities (ID) have spasticity, where increased
      muscle tone impairs activities of daily living (ADL) self-performance and care
      delivery. There are few reports of spasticity treatment for people with ID, and
      none of functionally meaningful outcomes. Our objective is to determine the
      effect of comprehensive spasticity management on ADL self-performance and care
      delivery. Baseline evaluation included repeated modified Ashworth and range of
      motion assessments, and timed and videotaped care task observations. Spasticity
      treatment was initiated immediately thereafter. Follow-up evaluation was
      conducted after spasticity management was optimized, one year after initiation.
      All individuals with spasticity at a single developmental center for whom
      treatment goals could be identified were included. Treatment was recommended by a
      neurologist from any accepted treatment for spasticity except oral medications,
      including botulinum neurotoxin A, intrathecal baclofen and orthopedic procedures.
      The main outcome measure is comparison of ease of videotaped care delivery, rated
      by direct caregivers blinded to participant treatment status. Spasticity
      treatment resulted in significant improvement across all outcome measures. Range
      of motion improved by 9 degrees (P = 0.005) and MAS by 0.4 (P = 0.022).
      Participants took 14% percent less time to complete tasks post-treatment (P =
      0.01). Thirteen caregivers completed evaluations of 35 video pairs with an intra
      class correlation of 0.9. After treatment, undergarment change (P = 0.031) and
      shirt change (P = 0.017) were rated easier, and all goals (P = 0.0006). Transfers
      trended toward improvement (P = 0.053). This study shows comprehensive spasticity
      management provides meaningful improvement in ADL care for patients with ID,
      which may improve quality of life and reduce caregiver burden.

PMID- 20131402
TI  - Conditions for using FRAP as a quantitative technique--influence of the bleaching
      protocol.
AB  - Fluorescence recovery after photobleaching (FRAP) is a tool widely used in
      studies of dynamic behavior of fluorescently-tagged proteins in live cells. We
      have analyzed published data on dynamics of various nuclear proteins and note
      that FRAP protocols and methods of data analysis vary between laboratories. A
      question arises if the experimental protocol can influence the recovery times. To
      establish if the FRAP protocol can influence fluorescence half-recovery times, we
      used various FRAP protocols and studied the dynamics of a GFP-tagged H1 (linker)
      histone. We demonstrate that fluorescence half-recovery times depend on the
      bleaching protocol, including the photon flux of the bleaching light. Thus, we
      conclude that due to differences between protocols and ways of analyzing data,
      the existing body of information on mobility of various nuclear proteins does not
      permit direct comparisons between experiments from different laboratories. To
      exploit a full potential of FRAP as a quantitative technique, there is a need to
      establish ground rules for photobleaching protocols and adopt a consistent way of
      data analysis.

PMID- 20131403
TI  - Mammalian target of rapamycin regulates vascular endothelial growth factor
      dependent liver cyst growth in polycystin-2-defective mice.
AB  - Polycystic liver disease may complicate autosomal dominant polycystic kidney
      disease (ADPKD), a disease caused by mutations in polycystins, which are proteins
      that regulate signaling, morphogenesis, and differentiation in epithelial cells.
      The cystic biliary epithelium [liver cystic epithelium (LCE)] secretes vascular
      endothelial growth factor (VEGF), which promotes liver cyst growth via autocrine
      and paracrine mechanisms. The expression of insulin-like growth factor 1 (IGF1),
      insulin-like growth factor 1 receptor (IGF1R), and phosphorylated mammalian
      target of rapamycin (p-mTOR) and the protein kinase A (PKA)-dependent
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) are also up
      regulated in LCE. We have hypothesized that mammalian target of rapamycin (mTOR)
      represents a common pathway for the regulation of hypoxia-inducible factor 1
      alpha (HIF1alpha)-dependent VEGF secretion by IGF1 and ERK1/2. Conditional
      polycystin-2-knockout (Pkd2KO) mice were used for in vivo studies and to isolate
      cystic cholangiocytes [liver cystic epithelial cells (LCECs)]. The expression of
      p-mTOR, VEGF, cleaved caspase 3 (CC3), proliferating cell nuclear antigen (PCNA),
      IGF1, IGF1R, phosphorylated extracellular signal-regulated kinase, p-P70S6K,
      HIF1alpha, and VEGF in LCE, LCECs, and wild-type cholangiocytes was studied with
      immunohistochemistry, western blotting, or enzyme-linked immunosorbent assays.
      The cystic area was measured by computer-assisted morphometry of pancytokeratin
      stained sections. Cell proliferation in vitro was studied with 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      and bromodeoxyuridine assays. The treatment of Pkd2KO mice with the mTOR
      inhibitor rapamycin significantly reduced the liver cyst area, liver/body weight
      ratio, pericystic microvascular density, and PCNA expression while increasing
      expression of CC3. Rapamycin inhibited IGF1-stimulated HIF1alpha accumulation and
      VEGF secretion in LCECs. IGF1-stimulated LCEC proliferation was inhibited by
      rapamycin and SU5416 (a vascular endothelial growth factor receptor 2 inhibitor).
      Phosphorylation of the mTOR-dependent kinase P70S6K was significantly reduced by
      PKA inhibitor 14-22 amide and by the mitogen signal-regulated kinase inhibitor
      U1026. CONCLUSION: These data demonstrate that PKA-dependent up-regulation of
      mTOR has a central role in the proliferative, antiapoptotic, and pro-angiogenic
      effects of IGF1 and VEGF in polycystin-2-defective mice. This study also
      highlights a mechanistic link between PKA, ERK, mTOR, and HIF1alpha-mediated VEGF
      secretion and provides a proof of concept for the potential use of mTOR
      inhibitors in ADPKD and conditions with aberrant cholangiocyte proliferation.

PMID- 20131404
TI  - Critical role of interferon regulatory factor-1 in murine liver transplant
      ischemia reperfusion injury.
AB  - Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates
      gene expression during immunity. We hypothesized that IRF-1 plays a pivotal role
      in liver transplant (LTx) ischemia/reperfusion (I/R) injury. Mouse orthotopic LTx
      was conducted after 24 hours cold storage in University of Wisconsin (UW)
      solution in wildtype (WT) C57BL/6 and IRF-1 knockout (KO) mice. IRF-1 deficiency
      in liver grafts, but not in recipients, resulted in significant reduction of
      hepatocyte apoptosis and liver injury, as well as improved survival. IRF-1 mRNA
      up-regulation was typically seen in graft hepatocytes in WT-->WT LTx. Deficiency
      of IRF-1 signaling in graft resulted in significantly reduced messenger RNA
      (mRNA) levels for death ligands and death receptors in hepatocytes, as well as
      decreased caspase-8 activities, indicating that IRF-1 mediates death ligand
      induced hepatocyte death. Further, a smaller but significant IRF-1 mRNA up
      regulation was seen in WT graft nonparenchymal cells (NPC) and associated with
      interferon gamma (IFN-gamma) mRNA up-regulation exclusively in NPC. IFN-gamma
      mRNA was significantly reduced in IRF-1 KO graft. Thus, IRF-1 in graft
      hepatocytes and NPC has distinct effects in hepatic I/R injury. However, LTx with
      chimeric liver grafts showed that grafts lacking hepatocellular IRF-1 had better
      protection compared with those lacking IRF-1 in NPC. The study identifies a
      critical role for IRF-1 in liver transplant I/R injury.

PMID- 20131406
TI  - Short-term therapy with peroxisome proliferation-activator receptor-alpha agonist
      Wy-14,643 protects murine fatty liver against ischemia-reperfusion injury.
AB  - Steatosis increases operative morbidity/mortality from ischemia-reperfusion
      injury (IRI); few pharmacological approaches have been protective. Using novel
      genetic/dietary models of nonalcoholic steatohepatitis (NASH) and simple
      steatosis (SS) in Alms1 mutant (foz/foz) mice, we characterized severity of IRI
      in NASH versus SS and lean liver and tested our hypothesis that the lipid
      lowering effects of the peroxisome proliferation-activator receptor (PPAR)-alpha
      agonist Wy-14,643 would be hepatoprotective. Mice were subjected to 60-minute
      partial hepatic IRI. Microvascular changes were assessed at 15-minute reperfusion
      by in vivo microscopy, injury at 24 hours by serum alanine aminotransferase
      (ALT), and hepatic necrosis area. Injury and inflammation mediators were
      determined by way of immunoblotting for intercellular cellular adhesion molecule,
      vascular cellular adhesion molecule, p38, c-jun N-terminal kinase, IkappaB-alpha,
      interleukin (IL)-1a, IL-12, tumor necrosis factor-alpha (TNF-alpha) and IL-6,
      cell cycle by cyclin D1 and proliferating cell nuclear antigen
      immunohistochemistry. In foz/foz mice fed a high-fat diet (HFD) to cause NASH or
      chow (SS), IRI was exacerbated compared with HFD-fed or chow-fed wild-type
      littermates by ALT release; corresponding necrotic areas were 60 +/- 22% NASH, 29
      +/- 9% SS versus 7 +/- 1% lean. Microvasculature of NASH or SS livers was
      narrowed by enormous lipid-filled hepatocytes, significantly reducing numbers of
      perfused sinusoids, all exacerbated by IRI. Wy-14,643 reduced steatosis in NASH
      and SS livers, whereas PPAR-alpha stimulation conferred substantial
      hepatoprotection against IRI by ALT release, with reductions in vascular cellular
      adhesion molecule-1, IL-1a, TNF-alpha, IL-12, activated nuclear factor-kappaB (NF
      kappaB), p38, IL-6 production and cell cycle entry. CONCLUSION: NASH and SS
      livers are both more susceptible to IRI. Mechanisms include possible distortion
      of the microvasculature by swollen fat-laden hepatocytes, and enhanced production
      of several cytokines. The beneficial effects of Wy-14,643 may be exerted by
      dampening adhesion molecule and cytokine responses, and activating NF-kappaB, IL
      6 production, and p38 kinase to effect cell cycle entry.

PMID- 20131405
TI  - Role of transforming growth factor beta signaling and expansion of progenitor
      cells in regenerating liver.
AB  - Adult hepatic progenitor cells are activated during regeneration when hepatocytes
      and bile duct epithelium are damaged or unable to proliferate. On the basis of
      its role as a tumor suppressor and in the potential malignant transformation of
      stem cells in hepatocellular carcinoma, we investigated the role of key
      transforming growth factor beta (TGF-beta) signaling components, including the
      Smad3 adaptor protein beta2-Spectrin (beta2SP), in liver regeneration. We
      demonstrate a streaming hepatocyte-specific dedifferentiation process in
      regenerating adult human liver less than 6 weeks following living donor
      transplantation. We then demonstrate a spatial and temporal expansion of TGF-beta
      signaling components, especially beta2SP, from the periportal to the pericentral
      zone as regeneration nears termination via immunohistochemical analysis. This
      expansion is associated with an expanded remaining pool of octamer 3/4 (Oct3/4)
      positive progenitor cells localized to the portal tract in adult human liver from
      more than 6 weeks posttransplant. Furthermore, disruption of TGF-beta signaling
      as in the beta2SP (beta2SP+/-) knockout mouse demonstrated a striking 2 to 4-fold
      (P < 0.05) expanded population of Oct3/4-positive cells with activated Wnt
      signaling occupying an alpha-fetoprotein (AFP)+/cytokeratin-19 (CK-19)-positive
      progenitor cell niche following two-thirds partial hepatectomy. CONCLUSION: TGF
      beta signaling, particularly beta2SP, plays a critical role in hepatocyte
      proliferation and transitional phenotype and its loss is associated with
      activation of hepatic progenitor cells secondary to delayed mitogenesis and
      activated Wnt signaling.

PMID- 20131407
TI  - Rationale for the real-time and dynamic cell death assays using propidium iodide.
AB  - We have recently reported an innovative approach to use charged fluorochromes
      such as propidium iodide (PI) in the real-time, dynamic cell viability assays.
      This study was designed to provide a mechanistic rationale for the kinetic assays
      using cell permeability markers. Uptake of PI by live cells, effect on the cell
      cycle, long-term proliferation capacity, DNA damage response, and pharmacologic
      interactions with anticancer drugs were studied using both laser scanning
      microscopy and laser scanning cytometry. Exposure of human carcinomic alveolar
      basal epithelial A549 cells in cultures to 1.5 or 7.5 microM of PI for 24 h had
      minimal effect on cell cycle progression including DNA replication as measured by
      incorporation of 5'-ethynyl-2-deoxyuridine (EdU) detected by the "click
      chemistry" approach and measured by laser scanning cytometry. A modest reduction,
      from 44 to 40% or 33%, in frequency of DNA replicating cells was seen after 48 h
      at 1.5 or 7.5 microM concentration of PI. There was no evidence of increased
      phosphorylation of histone gammaH2AX in cells growing in the presence of 1.5 or
      7.5 microM of PI for up to 48 h. Confocal image analysis of HeLa and NIH 3T3
      mouse embryonic fibroblasts growing in the presence of PI showed granular
      distribution in cell cytoplasm suggesting PI accumulation in endosomes and
      progressive increase in fluorescence of nucleoli reflecting PI binding to
      nucleolar RNA. The overall responses of cells to cytotoxic agents were also not
      affected by the growth in the presence PI. Our data lend further support to the
      notion that PI can be effectively used in real-time, kinetic viability assays.

PMID- 20131408
TI  - Updating the skin sensitization in vitro data assessment paradigm in 2009--a
      chemistry and QSAR perspective.

PMID- 20131409
TI  - The hepatocytes of the brown trout (Salmo trutta fario): a stereological study of
      some cytoplasmic components with the breeding cycle.
AB  - Sex differences exist in fish hepatocytes, but studies for characterizing their
      cytology throughout the breeding cycle are still scarce; suggesting changes, but
      most lacking quantitative data. To address this limitation, to complement
      baseline data generated from the brown trout model, and to prove that sex
      specific seasonal changes exist, we made an unbiased stereological evaluation of
      the hepatocytic cytoplasm. Unprecedentedly for fish liver, the stereological
      design was exempt from model (biased) assumptions. Five (3 years old) animals per
      sex were studied in endogenous vitellogenesis, exogenous vitellogenesis, and
      spawning season end. Liver pieces for analysis were systematically sampled.
      Stereology was done in transmission electron microscopy (TEM) micrographs.
      Primary data generated relative volume estimates of the major cytoplasmic
      components. Such values were used for deriving absolute volumes (per cell and per
      liver). Lipid droplets did not show changes. As to other targets, trends at cell
      and liver levels were not always equal. If the hepatocyte was the reference
      space, the contents in mitochondria, dense bodies, glycogen, and cytosol changed
      seasonally, in both sexes. If taking the liver as the reference, changes attained
      the Golgi apparatus and rough endoplasmic reticulum (RER), besides dense bodies,
      glycogen (in females), and cytosol. The components volumes (namely per liver)
      were often positively (negatively for glycogen) correlated with the ovary weight,
      disclosing new associations and implications in fish. While also offering gold
      standard data for backing morphofunctional correlations and pathology, we
      revealed a new process by which females increase the amount of RER and Golgi
      throughout vitellogenesis, breaking from the idea on how this event happens in
      fish.

PMID- 20131410
TI  - The American Gastroenterlogical Association (AGA) Institute and Digestive Disease
      Week, May 17-22, 2008 San Diego, CA, USA. Abstracts.

PMID- 20131411
TI  - The American Gastroenterlogical Association (AGA) Institute and Digestive Disease
      Week, May 29- Jun 4, 2009, Chicago, Illinois, USA. Abstracts.

PMID- 20131412
TI  - Mobile computing platforms such as the iPhone are beginning to make inroads into
      the laboratory-serious prospect or fairy tale?

PMID- 20131413
TI  - Determining Atg protein stoichiometry at the phagophore assembly site  by
      fluorescence microscopy.
AB  - In eukaryotic cells, autophagy is a lysosomal/ vacuolar degradative pathway
      necessary for the turnover of different macromolecules. Autophagy is under
      precise regulation, not only qualitatively but also quantitatively, and excess or
      reduced levels of autophagy may lead to various human diseases. In yeast, genetic
      screens led to the identification of more than 30 autophagy-related (ATG) genes,
      and most of the gene products reside at the phagophore assembly site (PAS).
      However, our attempt to understand the quantitative properties of autophagy is
      usually hampered, because traditional methods of analysis cannot provide
      stoichiometric information. We have recently used a fluorescence microscopy-based
      method to study the stoichiometry of Atg proteins at the PAS, trying to explain
      the mechanism of how the vesicle formation process is precisely regulated. This
      article describes a practical guide on this method. Its application and further
      analysis will improve our understanding of the quantitative properties of
      autophagy.

PMID- 20131414
TI  - Proceedings of the Candidate Genes for Type 1 Diabetes Workshop, Washington, DC,
      USA, August 29, 2007 and October 22, 2008.

PMID- 20131415
TI  - Proceedings of The Lancet Conference on Healthcare-Associated Infections, 
      London, UK,  11-12 December 2008.

PMID- 20131416
TI  - Proceedings of the 4th TMS Symposium on Biological Materials Science, New
      Orleans, Louisiana, USA, 2008.

PMID- 20131417
TI  - [Chagas disease].

PMID- 20131418
TI  - [Presentation of the consensus workshop about the Chagas disease in non-endemic
      areas (26 June 2009, Paris, France)].

PMID- 20131419
TI  - [Chagas Carlos Justiniano Ribeiro (1879-1934)].
AB  - The story of the life of Carlos Chagas is closely associated with the discovery
      of American Human Trypanosomiasis, caused by Trypanosoma cruzi. Indeed, he worked
      on this for almost all of his life. Nowadays he is considered as a national hero,
      but, when he was alive, he was criticised more severely in his own country than
      elsewhere, often unjustly and motivated by jealousy, but sometimes with good
      reason. Cases of Chagas disease in non-endemic countries became such a concern
      that public health measures have had to be taken. In this article we give a short
      account of the scientific journey of this man, who can be said to occupy his very
      own place in the history of Tropical Medicine.

PMID- 20131420
TI  - [Sword of Damocles or Russian roulette ... what everyone knows or ought to know
      about Chagas disease].
AB  - In 2006 the Pan American Health Organisation (PAHO) roughly estimated the
      prevalence of Chagas disease or American Human Trypanosomiasis, due to
      Trypanosoma cruzi, still to be eight million cases. The migration of people from
      the country into towns has resulted, in recent decades, in the urbanisation of
      this rural disease. Up to the mid-20th century, the epidemiology of the disease
      was closely linked to the extreme poverty of the peasant population and to their
      housing, the rancho, which offers a suitable habitat for the vectors and
      encourages their proliferation. A further barrier has recently been crossed with
      the arrival in non-endemic areas of numerous seropositive individuals. We shall
      draw attention in this article to the main clinical signs and to the manner of
      progression of the disease as well as to the problems posed by treatment of the
      different phases of this unique condition. It is not fanciful to describe it as
      resembling an adventure story, because of the place and manner of its discovery
      and of how the disease unfolds.

PMID- 20131421
TI  - [Chagas disease in France: estimated number of infected persons and cardiac
      diseases in 2009, by risk groups].
AB  - An estimation of the number of Trypanosoma cruzi infected individuals and
      expected number of Chagasic cardiomyopathies in France (excluding French Guyana)
      was conducted in June, 2009 by InVS. Different risk groups were identified:
      Latino-Americans (LA) from endemic area (naturalized, legal and illegal migrants,
      adopted children), children born from LA's mother, French Guyanese living in
      Metropolitan France, expatriated and travellers from endemic countries.
      Prevalence rates by country of origin were applied to official data on risk
      populations obtained from the International Adoption Agency, Tourism Direction
      and French ministries (Finances, Foreign Affairs and Migrations). Around 157,000
      individuals were potentially exposed. It is estimated than 1,464 [895-2,619] are
      infected by T. cruzi, of which 63 to 555 may evolve towards a chronic
      cardiomyopathy. This figure is within the range of earlier estimations of InVS
      and Guerri-Guttenberg. Taking into account illegal immigrants, the expected
      number of infected individuals in France should increase greatly this estimation.

PMID- 20131422
TI  - [Chagas disease screening in the blood donor population].
AB  - In May 2007, the French Blood Service (Etablissement francais du sang, EFS)
      introduced systematic screening of at-risk blood donors for anti-Trypanosoma
      cruzi antibodies. This concerned donors originating from an endemic area, donors
      with mothers originating from such an area and individuals who had lived in or
      travelled to endemic areas, whatever the length of their stay. Five samples out
      of 163,740 were positive, all from individuals originating from an endemic area.
      One thousand three hundred seventy-four blood donations were considered as
      equivocal because they had discordant results on the two Elisa tests used in
      screening. The authors discuss difficulties presented by routine screening of
      travellers and residents as well as the advantages and drawbacks of the strategy
      used. They present arguments in favour of its simplification.

PMID- 20131423
TI  - [Experience of targeted screening of Chagas disease in Ile-de-France].
AB  - 2009 is marked by the centenary of the discovery by Carlos Chagas of Human
      American Trypanosomiasis. As a result of international cooperation its incidence
      has been falling in endemic areas, whereas North America and Europe are
      witnessing an increase in the number of imported cases. In metropolitan France,
      18 such cases were reported between 2004 and 2007. Recently, estimates based on
      immigration figures have been made and suggest that about 1,500 imported cases
      can be expected in France. The object of this article is to assess the value of
      targeted screening of an at-risk population, originally from Latin America and
      now living in the Ile-de-France (area centred on Paris). The serological
      techniques employed were indirect immunofluorescence (IIF) and, depending on the
      case, 2 or 3 Elisa tests (Biomerieux, Biokit and Wiener). Trypanosoma cruzi
      serology was considered positive when the IIF was superior or equal to 200, or
      when two Elisa's were > 1, or when the IIF was superior or equal to 100 with at
      least one Elisa > 1. PCR was performed in 48 cases, which were considered to be
      positive. The tests were carried out on a voluntary basis after a publicity
      campaign within the Latin American community in the Ile-de-France. In this
      article, we present the findings of the first year of screening. Two hundred and
      fifty-four individuals were screened for Chagas' disease between June 2008 and
      June 2009. The median age was 33 years [11-63], the male/female ratio 102/152.
      Overall prevalence of positive serology was 23.6% (60/254). For six patients, the
      results were classified as "uncertain" (discordant serological tests). Of the
      seropositive group, 87.4% were Bolivian and 100% presented as a chronic form. Of
      these, 23.6% presented with functional cardiac manifestations and 22% with gastro
      intestinal problems. The PCR was positive in 61% of the seropositive individuals.
      Clinical evaluation together with other investigations and therapeutic
      intervention is being carried out at present. These results confirm that
      metropolitan France is subject to the emergence of Chagas' disease in a non
      endemic zone. This confirms the value of screening in at-risk populations, in
      particular because of the recent broadening of indications for antiparasitic
      treatment. In addition it is relevant to the prevention of vertical transmission
      or infection via organ donation, which could arise in France. These results also
      demonstrate continuing difficulties in the interpretation of serological results
      and the usefulness of PCR, which might increase sensitivity substantially.

PMID- 20131424
TI  - [Screening for congenital infection by Trypanosoma cruzi in France].
AB  - The importance of congenital transmission of Chagas' disease increases with its
      emergence in communities infected with Trypanosoma cruzi, but where vector
      transmission has never existed or is fully controlled through vector control
      campaigns. In both endemic and non-endemic areas, the rates of mother-to-child
      transmission (MTCT) could be the same, by 5%, generating a constant source of new
      cases of the disease. Risk factors for vertical transmission are not fully
      elucidated, but the effectiveness of the adaptive immune response and the genetic
      susceptibility of both the mother and the child are suspected. Besides the risk
      of miscarriage or premature birth, neonatal infection by T. cruzi causes an acute
      form of Chagas disease, which may be accompanied by a severe infectious syndrome
      that can causes death if not treated early. This form of the disease is a real
      public health priority because it is frequent, severe, identifiable and curable.
      Indeed, almost all newborns diagnosed and treated before the end of their first
      year of life will be definitely cured. In all non-endemic areas, detection of
      cases of congenital Chagas disease is hampered by a very low prevalence of the
      disease in the general population of pregnant women, the lack of symptoms in most
      infected women and the disregard of these problems from health personnel in
      charge of monitoring pregnancy. Secondary prevention firstly consists in
      identifying infected women (with history of exposure and positive serology for
      Chagas disease) and secondly to look for the parasite in newborns from infected
      mothers. No primary prevention is indeed possible during pregnancy, since the
      only two drugs are toxic and possibly teratogenic. However, after birth,
      treatment could be offered to all infected women in order to prevent late
      complications of the disease and to make an attempt at breaking the chain of MTCT
      in future pregnancies.

PMID- 20131425
TI  - [Chagas disease and immunodeficiency: HIV infection and transplantation].
AB  - In the immunocompromised patients, the main features of Chagas disease are severe
      clinical manifestations during the acute phase and reactivations occurring during
      the chronic phase. Reactivation is defined by a demonstration of trypomastigots
      on microscopic examination of blood or the identification of amastigots on biopsy
      samples and/or acute clinical manifestations during the chronic phase. In HIV
      patients, meningo-encephalitis and myocarditis are the major clinical syndromes
      of reactivation. In transplanted patients, cutaneous lesions often reveal the
      reactivation. A parasiticidal treatment (nifurtimox or benznidazole) should be
      initiated immediately. A secondary prophylaxis is indicated for HIV patients with
      CD4 cells count < 200/mm3. In the near future, quantitative PCR could allow to
      diagnose early reactivation, to initiate preemptive therapy and to closely
      monitor the therapeutic response. Due to the severe manifestations and prognosis
      of Chagas disease in the immunocompromised host, two serologic tests must be
      performed in the patient with an history of residency in endemic countries.

PMID- 20131426
TI  - [Chagas disease in chronic phase outside the endemic area. The diagnostic tools].
AB  - The diagnosis of Chagas disease during the chronic phase is based on serology.
      Outside South America the use of two methods is recommended by WHO. A third
      method must be available for inconclusive results but there is no gold standard.
      A pilot study of screening in 254 Bolivian people living in the Paris area
      (France) was made. Serological study was performed using IIF and three Elisa,
      Elisa Cruzi (BioMerieux Bresil), BioElisa Chagas (Bio-kit), and Chagatest Elisa
      recombinante v. 3.0 (Wiener Lab). 165 patients were negative, 69 positive and 20
      inconclusive. PCR-based assays appear to have a better sensitivity than
      parasitological methods, but not more than 70% that do not justify their use for
      primary testing. There are no standardized and commercial assays. The primer
      pairs based on the nuclear sequence TCZ1-TCZ2 seems to be the more specific (no
      cross reaction with others Trypanosomatidae) and the most sensitive with the
      strains of the two lineage of Trypanosoma cruzi. PCR would have a role in
      inconclusive serological cases or in the evaluation of treatment failure.

PMID- 20131427
TI  - [Management of Chagas disease in Europe. Experiences and challenges in Spain,
      Switzerland and Italy].
AB  - The intention of this article is not to describe the illness or evaluate the
      number of cases diagnosed in Spain, Switzerland and Italy, nor to analyse the
      protocols followed in various centres. The authors rather seek to examine the
      main technical, local and national challenges involved in the care of patients
      with Chagas disease. To this end, they review concisely a number of themes which
      are common to the three countries. These are: the detection of disease;
      confirmation of the diagnosis; treatment; response to treatment; follow-up; the
      risk of transmission by transfusion, by organ donation and from mother to child;
      the psychosocial and socio-economic aspects of Chagas disease outside endemic
      areas; and what progress needs to be made in improving information about the
      condition.

PMID- 20131428
TI  - [Summary of Workshop. No1. Risk populations of Chagas disease in metropolitan
      France and congenital Chagas disease].

PMID- 20131429
TI  - [Report on round table discussions. No 2. Diagnosis, behaviour and monitoring of
      patients].

PMID- 20131430
TI  - [Report on round table discussions. No 3. Screening and biological diagnosis of
      Chagas disease].

PMID- 20131431
TI  - [Conclusion of the consensus workshop organized by the "Societe de pathologie
      exotique" about the Chagas disease in non-endemic areas (26 June 2009, Paris,
      France)].

PMID- 20131432
TI  - Recommendations made at the end of the consensus workshop organized by the
      Societe de pathologie exotique (Exotic Pathology Society) (Paris, 26 June 2009).

PMID- 20131433
TI  - [New type of human trypanosomiasis].

PMID- 20131434
TI  - Managers' anger at name and shame threat.

PMID- 20131435
TI  - Can the system do more to catch local 'failures'?

PMID- 20131436
TI  - On seeing into the future.

PMID- 20131437
TI  - Ride the wave of innovation.

PMID- 20131439
TI  - The fifty people with the greatest influence on NHS management policy and
      practice in 2009.

PMID- 20131438
TI  - Innovation. Switch on your culture of ideas.

PMID- 20131440
TI  - Human resources. Waving, not drowning.

PMID- 20131441
TI  - Legal. Controlling continuing costs.

PMID- 20131442
TI  - Personal health planning. Self fulfillment.

PMID- 20131443
TI  - Shared journey.

PMID- 20131444
TI  - Python boom.

PMID- 20131445
TI  - Safety outcry is 'mandate' for quality.

PMID- 20131446
TI  - Secure service referrals surge as prisons overfill.

PMID- 20131447
TI  - Nicholson presses case for vertical integration.

PMID- 20131448
TI  - John Lewis checked out in productivity drive.

PMID- 20131449
TI  - On scratching and grooming.

PMID- 20131450
TI  - Target inequalities, beat cancer.

PMID- 20131452
TI  - Joint finance. Focus funding plans on people--not processes.

PMID- 20131451
TI  - Have you the traits of a trailblazer?

PMID- 20131453
TI  - Older people. The national standard for intermediate care.

PMID- 20131454
TI  - Technology. Build a virtual polyclinic.

PMID- 20131455
TI  - Running (and walking) the talk: 2009 Life Healthcare Medical 10.

PMID- 20131456
TI  - One in five PCTS overspent as SHAs predict cash freeze.

PMID- 20131457
TI  - Could a swine flu surge see a slump in targets?

PMID- 20131458
TI  - Managers on the ropes.

PMID- 20131459
TI  - Take the fast track to efficiency.

PMID- 20131460
TI  - Risk management. A culture of safety keeps risk covered.

PMID- 20131461
TI  - Clinical coding. How to code with confidence.

PMID- 20131462
TI  - Much done, still more to do.

PMID- 20131463
TI  - Giving everyone the same chance.

PMID- 20131464
TI  - New figures are a clarion call for increased activity on health inequalities.

PMID- 20131465
TI  - Teamwork helps to share all the lessons that are learnt.

PMID- 20131466
TI  - Tackling the three big killers.

PMID- 20131467
TI  - Taking care out of the surgery into the community.

PMID- 20131468
TI  - Health partners who help with a personal touch.

PMID- 20131469
TI  - Make the most of the online tools.

PMID- 20131470
TI  - Life expectancy in Europe.

PMID- 20131471
TI  - Post-2010 we all have a role in closing the gap.

PMID- 20131472
TI  - Human resources. How the tough get going.

PMID- 20131473
TI  - Appointments. Patient choice is the only option.

PMID- 20131474
TI  - Taking the lead.

PMID- 20131475
TI  - On the way up.

PMID- 20131476
TI  - Development. Advancing with a purpose.

PMID- 20131477
TI  - Impaired parent-reported quality of life in treatment-seeking children with
      obesity is mediated by high levels of psychopathology.
AB  - PURPOSE: The purpose of the current study was to explore psychopathology as a
      mediator of quality of life (QOL) in children and adolescents with obesity. The
      notion that psychopathology and QOL are two distinct constructs was also tested.
      METHODS: A sample of treatment-seeking children and adolescents with obesity (n =
      185, average age = 11.5, mean BMI SDS = 3.03) was matched to a community sample
      of children (n = 799, average age = 11.5). Both self- and parent-reported
      measures of QOL (KINDL-R) and psychopathology (CBCL/YSR) was completed. RESULTS:
      Parent-reported QOL was impaired, and both self-reported and parent-reported
      psychopathology was elevated in children and adolescents with obesity.
      Psychopathology accounted for all the variance of the effect of obesity on parent
      reported QOL. The distinction between QOL and psychopathology was supported
      through confirmatory factor analysis. CONCLUSION: Impaired parent-reported QOL in
      children and adolescents with obesity was attributable to their elevated levels
      of psychopathology.

PMID- 20131478
TI  - Cloning and validation of novel miRNA from basmati rice indicates cross talk
      between abiotic and biotic stresses.
AB  - Most of the physiological processes are controlled by the small RNAs in several
      organisms including plants. A huge database exists on one type of small RNA,
      i.e., microRNAs (miRs) identified from diverse species. However, the processes of
      data-mining of miRs in most of the species are still incomplete. Rice feeds the
      hungry trillions and hence understanding its developmental processes as well as
      its stress biology, which might be largely controlled by the small RNA pathways,
      is certainly a worthwhile task. Here, we report the cloning and identification of
      approximately 40 new putative miRs from local basmati rice variety in accordance
      to the annotation suggested by Meyers et al. (Plant Cell 20:3186-3190, 2008).
      About 23 sequences were derived from rice exposed to salt stress while 18 were
      derived from rice infected with tungro virus. A few of these putative miRs were
      common to both. Our data showed that at least two of these miRs were up-regulated
      in response to both abiotic and biotic stresses. The miR target predictions
      indicate that most of the putative miRs target specific metabolic processes. The
      up-regulation of similar miRs in response to two entirely different types of
      stresses suggests a converging functional role of miRs in managing various
      stresses. Our findings suggest that more rice miRs need to be identified and a
      thorough understanding of the function of such miRs will help unravel the
      mysteries of rice stress biology.

PMID- 20131479
TI  - Factors associated with mortality in hospitalized patients with newly diagnosed
      tuberculosis.
AB  - The purpose of this study was to identify clinical and epidemiological factors
      associated with death in patients with an in-hospital diagnosis of tuberculosis
      (TB), in a city with a high prevalence of TB and human immunodeficiency virus
      (HIV) infection. The study was a retrospective, cohort study conducted at a
      general, tertiary-care, university-affiliated hospital. Patients who began
      treatment for TB after hospitalization were included. Predictors of mortality
      were assessed. The primary outcomes were the in-hospital mortality and the
      mortality after discharge. We evaluated the medical records of 311 patients with
      TB. The overall mortality rate of all study participants was 99/311 (31.8%). The
      mortality rates during hospitalization and after discharge were 50/311 (16.1%)
      and 49/261 (18.8%), respectively. Mechanical ventilation, consolidation in chest
      X-ray, and negative sputum smear were predictors of in-hospital death in
      multivariate analysis. Independent predictors of mortality after discharge in
      multivariate analysis included total duration of hospitalization and being a
      current smoker. We found a high overall mortality rate for patients hospitalized
      with TB in a region with a high prevalence of TB and HIV. The risk of mortality
      once patients with TB are hospitalized is unlikely to be explained only by the
      HIV epidemic.

PMID- 20131481
TI  - 3D controversy.

PMID- 20131480
TI  - Double burden of underweight and overweight among children (10-19 years of age)
      of employees working in Indian industrial units.
AB  - BACKGROUND: Along with the existing problem of underweight, overweight in
      children is increasing in the developing world. However, there is little
      information on its magnitude and pattern in the Indian context. We aimed to study
      the pattern and correlates of overweight in Indian children and adolescents.
      METHODS: A total of 3750 children in the age group of 10-19 years, who were
      family members of randomly selected employees from 10 different industrial sites
      in India, were surveyed using an interviewer-administered questionnaire. RESULTS:
      The prevalence of underweight was highest in peri-urban areas (30.2% and 53.2%
      according to Indian and international criteria, respectively). In urban and
      highly urban areas, the prevalence of underweight was 14.1% and 9.8%,
      respectively, according to the Indian criteria, and 27.1% and 19.2%,
      respectively, according to international criteria. The proportion of overweight
      children was highest in the highly urban category (19.1% and 13.4% according to
      Indian and international criteria, respectively). The level of urbanization (OR
      3.1 and 4.7 for overweight in urban and highly urban areas, respectively,
      compared with peri-urban areas, p < 0.001), physical activity (OR 0.4, p < 0.001,
      in children with physical activity score > or = 75th percentile compared with a
      score < or = 75th percentile) and frequency of meals outside the home (OR 12, p <
      0.001, if > 25% weekly meals taken outside the home compared with < 25% of weekly
      meals outside home) were significant predictors of overweight. CONCLUSION: There
      is a double burden of underweight and overweight among Indian children and
      adolescents.

PMID- 20131483
TI  - "Cretins" and "idiots" in an Austrian alpine valley in the late 19th and early
      20th centuries: interests, social norms, and institutions involved in the
      attribution of "imbecility".

PMID- 20131484
TI  - A typology of nineteenth-century police.

PMID- 20131485
TI  - Weak bodies? Prostitutes and the role of gender in the criminological writings of
      19th-century German detectives and magistrates.

PMID- 20131487
TI  - [Between the ideal of charity and security policy: prevention according to the
      Prussian "Landrecht" of 1794].

PMID- 20131488
TI  - [The "Court of 19 August 1944": an essay on the remembrance of policemen].

PMID- 20131489
TI  - [Public health: strategies, fiscal policies, and cultural change in the reduction
      of mortality. Valparaiso, 1920-60].

PMID- 20131490
TI  - [A judicial contest between two women: suits and sentiments, 1773-75].

PMID- 20131491
TI  - [Business, family, and the public sphere: the case of Navarre, 1830-1913].

PMID- 20131492
TI  - [The history of the family in Navarre: a qualitative approach].

PMID- 20131493
TI  - In China, the veterinary profession unites.

PMID- 20131494
TI  - CEM outbreak took its toll on U.S.

PMID- 20131495
TI  - A systematic review of compliance with palivizumab administration for RSV
      immunoprophylaxis.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower
      respiratory tract infection (LRTI) in infants and young children, accounting for
      approximately 75,000-125,000 hospitalizations per year. It is estimated that in
      2000, RSV infection accounted for 1.7 million office visits, 402,000 emergency
      room visits, and 236,000 hospital outpatient visits per year for children younger
      than 5 years of age. Palivizumab, a humanized monoclonal antibody directed
      against RSV, is the only immunoprophylaxis therapy approved by the FDA for
      prevention of serious lower respiratory tract disease caused by RSV in infants
      (up to 2 years of age) who meet 1 or more of the following criteria for high
      risk: (a) gestational age up to 35 weeks;(b) diagnosis of chronic lung disease
      (CLD, formerly bronchopulmonary dysplasia [BPD]); or (c) diagnosis of cyanotic or
      complex congenital heart disease. The RSV season typically occurs between
      November and March but may vary by region. During the period of our review,
      depending on local duration of the RSV season, infants usually required 5 monthly
      (every 28-30 days) intramuscular injections of palivizumab. Infants born in the
      middle of the season received their palivizumab doses from the time of birth to
      the end of the season and, therefore, may have required less than 5 doses.It is
      unclear if compliance with monthly doses is a problem and whether noncompliance
      increases the risk of RSV hospitalizations in routine clinical practice.
      OBJECTIVES: To (a) identify and describe compliance rates and the factors that
      influence parental compliance with immunoprophylaxis regimens, (b)review
      intervention programs and describe those that have been associated with increased
      compliance, and (c) summarize the association of compliance with RSV
      hospitalization rates. METHODS: An electronic literature search was conducted
      using journal databases, including Ovid, Current Contents, Embase, Medline In
      Process & Other Non-Indexed Citations; Ovid Medline, PubMed, and Web of
      Science;and an abstract database, Medical Intelligence Solution, for citations
      through April 2008. Specific search terms used were palivizumab with patient
      compliance, patient adherence, or patient persistence. RESULTS: Twenty-five
      articles and abstracts met the inclusion criteria. Available studies were mostly
      retrospective or observational prospective.Compliance, defined in various ways
      across the studies, varied between 25% and 100%, and 12 studies identified some
      of the factors related to noncompliance. Compliance generally was lower among
      Medicaid patients,African American patients, and other minorities. Ten studies (3
      manuscripts and 7 abstracts) investigated the association of administration of
      prophylaxis through monthly home visits by a health professional with parental
      compliance with therapy. Most of the home-based programs were associated with
      higher compliance rates compared with clinic or office programs.Rates as high as
      94% and 64% were achieved when Medicaid infants and infants of minority descent,
      respectively, received their doses through a home health program. When these
      infants received their doses at a clinic or office, depending on the definition
      of compliance, rates were 61%-100% for Medicaid infants and 44% for infants of
      minority descent. Reminder telephone calls to parents or caregivers,
      comprehensive multidisciplinary programs that included extensive counseling of
      parents, calendars with sticker reminders, and education in the language native
      to parents also were associated with increased compliance, although statistical
      significance was reported in only 1 study. Several studies recommended educating
      parents on the benefits of RSV prophylaxis, alleviating transportation and
      language difficulties, recognizing cultural differences and biases, and
      clarifying misperception of RSV illness severity. Home health programs had lower
      rates of RSV hospitalizations than office-based programs in 3 analyses conducted
      in 2 studies. In 4 other abstracts, the rates of RSV hospitalization for home
      health programs and office-based administration did not significantly differ. In
      a large, 4-season, prospective outcome study, compliant infants had lower RSV
      hospitalization rates than those who were not compliant under one definition of
      compliance (doses within 35-day intervals). RSV hospitalization rates were not
      significantly different using another definition of compliance (receipt of
      anticipated doses, expected vs. observed rates).In a large survey of 10,390
      infants identified from pharmacy dispensing records, RSV hospitalization rates
      were 1.4% in the compliant group versus 3.1% in the noncompliant group (OR = 2.2,
      95% CI = 1.4-3.5, P < 0.001).Adjustment for confounding was not reported in these
      studies. CONCLUSION: Medicaid and minority infants were less likely to receive
      scheduled palivizumab doses. Home-based programs for the administration of
      palivizumab have been investigated more than other interventions and are
      associated with improved compliance compared with office-based administration.
      Compliance with dosing, in general, was associated with lower RSV hospitalization
      rates. However, these strategies should be further investigated using well
      designed studies.

PMID- 20131496
TI  - From the editor's desk. The maintenance of intellectual faculties.

PMID- 20131497
TI  - [The Saint Petersburg Society of Pathologists is 100 years old].
AB  - The paper describes the history of the Saint Petersburg Society of pathologists
      since it was founded in 1909. It shows what great role is played by outstanding
      Russian medical scientists who have established their own schools of
      pathomorphologists and are respected in our and foreign countries. The activities
      of the society's members in research developments in cardiovascular and
      infectious diseases, cancer morphology, etc., as well as their practical
      participation in the work of the health care facilities of the city and its
      region are characterized. This work is characterized by the permanent conformance
      to the world standards of human pathology as a basic science of the present day,
      by steadily maintaining the established traditions of the Saint Petersburg
      school. The authors follow the evolution of a pathologist and his/her becoming to
      a clinical pathologist as the problems facing pathomorphology are extended and
      its methodic and methodological capacities are improved.

PMID- 20131498
TI  - [The specific features of the expression of molecular biological markers for
      proliferation and apoptosis in patients with lung cancer with epidermal growth
      factor receptor mutation].
AB  - Two hundred and two lung adenocarcinomas were examined for epidermal growth
      factor receptor (EGFR) mutation: exon 19 deletion and L85R mutation in exon 21.
      The expression of EGFR, Ki-67, bcl-2, p53 in the lung adenocarcinomas was studied
      in relation to the type of EGFR mutation. Lung adenocarcinomas harboring the EGFR
      L858R mutation in exon 21 have a less proliferative activity than those with EGFR
      mutation in exon 19 and in those without EGFR mutation. The p53 protein
      expression was higher in a group of adenocarcinomas having the EGFR L858R
      mutation than in that of adenocarcinomas with EGFR mutation in exon 19. There was
      no bcl-2 expression in adenocarcinomas showing the EGFR mutation.

PMID- 20131499
TI  - [Expression of cytokeratins in tumors with perineural differentiation].
AB  - Twenty tumors with perineural differentiation (1 intraneural perineurioma, 10
      conventional soft tissue perineuriomas, 3 reticular, 3 sclerosing, 1, atypical,
      and 2 malignant ones) were studied using a panel of antibodies directed against
      epithelial antigens. Seven (35%) cases were stained for CK14, 3 (15%) for
      AE1/AE3, and 2 (10%) for CAMS.2. These tumors showed focal expression of
      cytokeratins with labeling only a portion of cytoplasm. All tumors were negative
      for CEA, CK5/6, CK7, CK8, CK10, CK13, CK18, CK19, and CK20. The results of this
      investigation may be useful in the differential diagnosis of perineural tumors.

PMID- 20131500
TI  - [Analysis of survival rates in patients and prognostic models in non-metastatic
      clear-cell renal cell carcinoma].
AB  - The Cox multivariate regression analysis of survival rates in patients with non
      metastatic clear-cell renal cell carcinoma, by taking into account both various
      clinical, anatomic, morphometric, and biomolecular factors and kariometric
      parameters, has revealed that Ki-67 and p53 expression rates along with
      histologic grade, a tumor portion made up of clear-cell components, and the
      presence/absence of tumor invasion into paranephral fat tissue are independent
      prognostic predictors of the disease. By applying the proposed three prognostic
      models (algorithms) using Ki-67 and p53 expression rates for predicting the
      corrected survival rates for patients with non-metastatic clear-cell renal cell
      carcinoma, the authors suggest that a combined biomolecular-morphometric model is
      of the greatest prognostic value.

PMID- 20131501
TI  - [The proliferative properties and regulators of the mitotic cell cycle of
      prostate adenocarcinoma].
AB  - The authors have made an immunohistochemical determination of Ki-67,
      topoisomerase IIalpha, cyclins D1, A, and B1, and calculated their indices in 145
      acinar adenocarcinomas of the prostate. This tumor is characterized by a wide
      range of Ki-67 index (from 3 to 90% or more) although 90% of cases are in the
      range of 5-35%. Other study proliferative markers are distributed in the
      following descending order: cyclin D1 (1.32 to 63.27%), topoisomerase IIalpha
      (0.47 to 53.17%), cyclin A (0.46 to 28.09%), and cyclin B1 (0.29 to 9.34%). The
      indices of the study markers are increased as the Gleason grade is higher. The
      exception is cyclin D1 that shows high expression in intact and tumor tissues,
      which is frequently greater than that of Ki-67, and its stable expression
      independent of the Gleason score.

PMID- 20131502
TI  - [Morphological diagnosis of myeloid sarcomas].
AB  - Myeloid sarcoma (MS) is an extramedullary tumor made up by myeloid blasts that
      may be undifferentiated or show varying degrees of maturation. This paper gives
      the results of morphological and immunohistochemical studies of 15 cases of MS.
      The patients' age was 32.7 +/- 14.3 years. The most involvement was observed in
      lymph nodes (6 cases) and vertebral bodies with spread to the epidural space and
      soft tissues (3 cases). Differentiated MS was diagnosed in 60% of cases. The
      immunohistochemical profile of MS was characterized by the expression of MPO
      (100%), CD68 (92.8%), CD34 (77%), CD 117 (53.8%), lysozyme (50%), and TdT
      (44.4%). The blast structure similarity of myeloid blasts and other cells to
      chromatin makes MS difficult to diagnose. Without immunohistochemical study, MS
      is misdiagnosed and most frequently misinterpreted as one of the types of non
      Hodgkin's lymphoma.

PMID- 20131503
TI  - [Morphological characteristics of HCV cirrhosis of the liver].
AB  - Pathomorphological changes were analyzed in the HCV-cirrhotic liver of patients
      with varying decompensation of the organ 's function. The decompensation of liver
      function in HCV cirrhosis was shown to be directly related to the infectious
      process. It is conceivable that it is to a greater degree determined by an
      autoimmune response, as confirmed by lower blood virus replicative activity, NS3
      protein expression in the cells of an inflammatory infiltrate in the portal
      tract, and reduced detection rates for NS3 protein expression in the hepatocytic
      cytoplasm as the pathological process progresses.

PMID- 20131504
TI  - [Constitutional types of the structure of the cerebral arterial ring and their
      role in the development of aneurysmal disease].
AB  - One hundred and twenty patients who died in 2003 to 2008 were examined; of them
      27 patients died from ruptured aneurysm of the cerebral arterial ring (CAR).
      Vascular anthropometry and morphometry were made. Correlation analysis revealed a
      close direct correlation between the perimeters of elastic vessels (the aorta)
      and those of vessels of muscular type (the major arteries of the basis cerebri)
      and a close inverse correlation between the perimeters of the above arteries and
      human height. On the basis of these data, the authors identified three
      constitutional types of CAR: hypoplastic, normoplastic, and hyperplastic. The
      distribution by age and height (somatotype) in the variational series made up of
      those who had died from ruptured aneurysm was found to be bimodal. The clinical
      and morphological comparisons of the course of aneurysmal disease in these
      subgroups can identify two constitutional risk groups for development of
      aneurysmal disease: dysplastic and involutionally hypertensive.

PMID- 20131505
TI  - [The morphological and immunohistochemical features and malignancy potential of a
      hyalinizing trabecular tumor of the thyroid].
AB  - The paper considers the morphological features of a rare hyalinizing trabecular
      tumor of the thyroid, which is of follicular cell origin. The signs of invasive
      tumor growth into to the intrinsic capsule and its blood vessels were observed in
      2 of 7 cases. There was a positive immunohistochemical reaction of tumor cells
      with antibodies to thyroglobulin and neuron-specific enolase and a negative one
      to calcitonin, galectin 3, cytokeratin 19, and HBME-1. The differential diagnosis
      of a tumor and papillary and medullary carcinomas of the thyroid, as well as its
      malignancy potential are discussed in the paper.

PMID- 20131506
TI  - [Epitheliod hemangioendothelioma of the lung].
AB  - The authors give a morphological and immunohistochemical description of
      epitheliod hemangioendothelioma of the lung in two women aged 62 and 74 years.
      Evident neovascularization capacity, a significant tumor cell intracytoplasmic
      lumen frequently packed with red blood cells, and positive immunohistochemical
      reactions to endothelial antigens are of prime importance in making its
      diagnosis.

PMID- 20131507
TI  - [Primitive neuroectodermal tumor of the kidney in children; its differential
      diagnosis with Wilms tumor].
AB  - There may be a number of tumors made up by small round blue cells in the kidneys
      of children. One of them is primitive neuroectodermal tumor (PNET). The
      differences in therapeutic approaches determine the need to establish an accurate
      diagnosis. The differential diagnosis of PNET and the blastemal component of
      Wilms tumor can be difficult due to the similar histological pattern. There is a
      need for a close analysis of morphological manifestations, by keeping in mind the
      age of patients, and supplementary studies. A strong CD99 membrane expression and
      nuclear FLI1 expression in tumor cells are the signs of PNET. Reverse
      transcriptase-polymerase chain reaction and fluorescence in situ hybridization
      can determine PNET-specific translocations [t(11;22)(q24;q12), by involving the
      EWS gene.

PMID- 20131508
TI  - [Monophasic angiomyolipoma (PEComa) of the liver].
AB  - The paper provides a morphological and immunohistochemical description of hepatic
      angiomyolipoma in a 29-year-old woman. Microscopically, it is a tumor with
      trabecular and diffuse growth patterns, which consists of polygonal cells with
      pleomorphic nuclei and extensive cytoplasm accumulated around the nucleus.
      Immunohistochemical study is of crucial importance in making the diagnosis. The
      tumor cells coexpress smooth muscle actin and the melanin markers: HMB-45, melan
      A, and MITF. The proliferative activity of the tumor is very low (Ki-67 index <
      1%). According to the present views, angiomyolipoma belongs to perivascular
      epithelioid cell tumors (PEComas).

PMID- 20131509
TI  - [Plasma membrane focal defects in structurally normal cells].
AB  - The technique of perfusion fixation through the rat kidney vasculature was
      modified to ensure the highest possible level of cell preservation close to that
      under in vivo conditions. Electron microscopic analysis of the tissue specimens
      treated in such a way revealed local defects of the plasma membrane in a number
      of cells than that otherwise looked normal. These findings together with the
      evidence for reparability of such defects and some data on the purely artificial
      nature of certain alterations should be taken into consideration in order to
      avoid misinterpretations while diagnosing the biopsy specimens.

PMID- 20131510
TI  - [Efficiency of immunohistochemical study of high-molecular-weight cytokeratins
      (CKR-HMW) and p63 in prostate trepan biopsy specimens for establishing the
      diagnosis of adenocarcinoma].
AB  - Early diagnosis of prostate cancer is one of the most important problems of
      modern oncology. Trepan biopsy and further histological investigation are the
      standards for examination of patients with prostate neoplasms. Our investigations
      of 56 cases have indicated that in 27% of the cases, histological investigation
      is insufficient to make a valid diagnosis. In such cases, immunohistochemical
      evaluation of the expression of high-molecular-weight cytokeratins and p63 allows
      differentiation of carcinoma from benign masses of the prostate, which may be
      used to enhance the efficiency of early diagnosis of prostate cancer.

PMID- 20131511
TI  - [Mathematical stimulation for the determination of prognosis in renal cancer].
AB  - The paper describes the most accurate models of the existing mathematical ones
      based on the clinical, pathological, and/or biomolecular predictors that can
      determine the indicators of different types of survival in patients with renal
      cell carcinoma. The absence of highly accurate algorithms and nomograms suggests
      a further search for optimal disease prognosis models. The development of
      combined systems using the biomolecular markers of different histotypes of renal
      cell carcinoma is most promising.

PMID- 20131512
TI  - How to anticipate and deal more effectively with head injuries.

PMID- 20131513
TI  - The personality and socio-cultural factors associated with head injury.

PMID- 20131514
TI  - Predispositions to outcome.

PMID- 20131515
TI  - Limiting the damage and return to work.

PMID- 20131516
TI  - Revalidation and accreditation of medical expert witnesses: the next step.

PMID- 20131517
TI  - [Therapeutic gases for newborns: recent developments and future perspectives].
AB  - In respiratory care some gases are generally used to support the ventilation.
      Though oxygen is the most frequently dispensed, other specialty gases has become
      common practice in the last years. This report reviews the literature concerning
      the four gases mainly utilized in Neonatal Intensive Care Unit (NICU). Inhaled
      Nitric oxyde is a selective pulmonary vasodilator largely employed in NICU, while
      the helium-oxygen mixture, also knows as heliox, is less common, although it is
      widely note both the capability of decrease the pressure and work of breathing
      necessary to ventilate the lung, and the improvement of gas exchange in
      particular clinical situations. Carbon dioxide is generally used in the
      management of a specific congenital heart defect, and xenon, already known for
      its aesthetic proprieties but rarely used, because of its neuroprotective
      effects, could play a role in neonatal hypoxia/ischemia syndrome.

PMID- 20131518
TI  - [Pediatric flat foot: a review].

PMID- 20131519
TI  - [Foreign body ingestion in children: our experience and review of the
      literature].
AB  - Foreign body ingestion is a frequent event in paediatric population, especially
      in the first six years of life. Even if the event is normally cause of anxiety
      for the parents witness of the situation, fortunately most ingested foreign
      bodies ingestion, about 80-90%, pass spontaneously, 10-20% of cases needs an
      endoscopic intervention and only in less than 1% of cases surgery is necessary.
      Many authors suggest different guide-lines for diagnosis and therapy of foreign
      body ingestion in children. These purposes are discordant not only on potential
      danger of foreign body, but also on timing and last of waiting period before
      endoscopic extraction. Here we report our own experience: a retrospective review
      of three hundred consecutive paediatric cases of foreign body ingestion between
      June 2001 and February 2008. This study don't take in account patients with
      pathology either organic either functional, that can cause stop of food
      progression. We describe and discuss about medical diagnostic and therapeutic
      procedures that have been done during the time of hospitalization and performed
      according to classic and new international literature, with the objective to
      propose recommendations helpful for a correct management of children presenting
      with a history of suspected ingestion of a foreign body.

PMID- 20131520
TI  - Completely isolated enteric duplications cysts: a survey of four cases.
AB  - Enteric duplication cysts are uncommon congenital abnormalities with epithelial
      lining. They are cystic or tubular structures intimately attached to a portion of
      the gastrointestinal tract; they are usually located on the mesenteric site of
      the digestive tract sharing common blood supply. Isolated cystic duplications are
      an extremely rare variant with their own blood supply: in literature only five
      cases have been reported. We present our four cases series of this uncommon
      anomaly.

PMID- 20131521
TI  - Evolution of the surgical management of bowel atresia in newborn:
      laparoscopically assisted treatment.
AB  - PURPOSE: The jejunal-ileal atresias are the most common cause of intestinal
      occlusion in neonatal period and the duodenal atresia is the most common cause of
      high bowel obstruction in newborn. The treatment classically used is performed by
      a transverse sovraumbilical laparotomy. The first "minimal-invasive" approach was
      performed at the end of the years '70. Nowadays three clusters of thought are
      delineated about of mini-invasive treatment of small bowel atresias: the
      intestinal continuity can be established with a circumbilical incision, a totally
      laparoscopic technique or a laparoscopically assisted approach. It's presented
      our initial experience of bowel atresia in newborn treated with laparoscopically
      assisted approach. MATERIALS AND METHODS: Three newborns with prenatal diagnosis
      of suspected bowel obstruction and one with suspected duodenal atresia, confirmed
      the diagnosis after birth, underwent to laparoscopically-assisted surgery to
      correct these congenital anomalies. We have treated with this procedure a
      duodenal atresia, two jejunal atresias and an ileal form. Surgical management was
      consisted of an explorative laparoscopy that allowed to recognize and isolate the
      pathological portion. The second step was traditional open surgery: after the
      exteriorization of the pathological tract through the umbilical wound, we
      performed the intestinal anastomosis. RESULTS: In all cases the operation was
      completed successfully, no conversion was necessary. Intraoperatively no
      complications occurred. The post-operative course was uneventful. CONCLUSION: The
      video-assisted technique for the correction of small bowel atresia adds the
      advantages of the classic laparotomic procedure to the laparoscopic ones.

PMID- 20131522
TI  - [Monolateral macro-orchidism as an isolated feature of McCune-Albright syndrome].

PMID- 20131523
TI  - Second toe transplantation to reconstruct digits.
AB  - In congenital absence of fingers or in post-traumatic amputations of the thumb or
      fingers, reconstruction by microsurgical toe-to-hand transfer is becoming a
      common treatment for these difficult problems. In case of congenital absence of
      the thumb, fingers, or both, these transfers can provide acceptable growth,
      function and sensation of the transferred toes with a current success rate
      usually greater than 95%. The most commonly transplanted toe is the second toe,
      since it is the longest toe and combines all the useful characteristics of a
      finger (such as joint, a nail, sensitive pulp tissue, and the ability to growth)
      with a good reliable blood supply. In this article, we discuss the rationale for
      this treatment approach, by considering the indications to treatment, the
      patient's preoperatory assessment, and the long-term results. We also report a
      case of a 4-year-old female child, suffering from congenital partial absence of
      second finger of the left hand, who underwent reconstruction by transfer of the
      second toes of foot.

PMID- 20131524
TI  - Medical profession under unprecedented levels of scrutiny in recent years.

PMID- 20131525
TI  - Surgical report cards: the myth and the reality.
AB  - There seems no good reason for doctors to work in secret. Individual users of
      healthcare and the community in general, which ultimately bears the cost, are
      perfectly entitled to know how their health services and health providers are
      performing. The promulgation of surgical report cards has been hailed by some as
      a liberating step in the right direction. This paper seeks to analyse, from a
      clinician's perspective, the evolution and limitations of report cards.
      Ultimately, the importance of report cards will not be their immediate utility,
      which is minimal, but as a first step in a much wider and far more important
      debate about how we meaningfully measure the quality of health services and
      providers (including managers and bureaucrats), the likely cost of such an
      enterprise, how much we are willing and able to pay and how we reconcile the
      competing needs of information versus clinical and preventive care when all are
      competing for the same and inadequate pool of resources.

PMID- 20131526
TI  - Surgeon report cards, clinical realities, and the quality of patient care.
AB  - In this article, I respond to Alan Henderson's critique of the quality of care
      argument for surgeon report cards. I discuss some significant US and UK studies
      demonstrating that surgeon report cards improve clinical outcomes. I also
      indicate that surgeon report cards are in any case supported by other important
      ethical arguments, such as arguments from surgeons' professional accountability
      obligations, and from patients' entitlements to be informed about the risks of
      surgery upon them.

PMID- 20131527
TI  - Bioethics and birth: insights on risk decision-making for an elective caesarean
      after a prior caesarean delivery.
AB  - This article presents the findings of qualitative research which explored, from
      the mothers' perspective, the process of decision-making about mode of delivery
      for a subsequent birth after a previous Caesarean Section. In contradiction to
      the clinical literature, the majority of mothers in this study were strongly of
      the opinion that a vaginal birth after caesarean (VBAC) posed a higher risk than
      an elective caesarean (EC). From the mothers' perspective, risk discussions were
      primarily valuable for gaining support for their pre-determined choice, rather
      than obtaining information. The findings posit ethical concerns with regards to
      informed consent and professional obstetric practice at a time when there is a
      documented and worrying trend towards an increase in births by caesarean section
      (CS).

PMID- 20131528
TI  - Lateral violence: it's time to stop this blight on our profession.

PMID- 20131529
TI  - So many names for bad behavior?

PMID- 20131531
TI  - Quality in surgery. A change of attitude.

PMID- 20131530
TI  - Ethical and legal resources that relate to lateral violence.

PMID- 20131532
TI  - Inflammatory abdominal aortic aneurysm (IAAA).
AB  - PURPOSE: The aim of this study is to report our experience about the inflammatory
      abdominal aortic aneurysm (IAAA). METHODS: Between January 1999 and January 2008
      we treated 8 cases of IAAA. Two patients underwent surgery in emergency. The
      preoperative diagnostic procedure were ultrasound (US), computed tomography (CT)
      and intravenous urography (IVU). In 6 elective patients the diagnosis of IAAA was
      obtained preoperatively. In one case a left hydroureteronephrosis was
      demonstrated by intravenous urography (IVU). All patients underwent open surgery
      with midline incision and transperitoneal access. RESULTS: No 30-days mortality
      occurred. A case of pancreatitis was treated with conservative therapy. All
      patients had 60-days corticosteroid therapy. CONCLUSIONS: Our datas suggest that
      because IAAA have the same rate of rupture of AAA, they need the same preventive
      treatment as non inflammatory abdominal aortic aneurysm (AAA). The kind of
      approach OPEN-EVAR should be chosen with the same criteria as AAA, even if EVAR
      treatment doesn't allow us to obtain the biopsy. Furthermore there are no
      sufficient evidences about regression of retroperitoneal fibrosis after EVAR
      treatment. Also the premature onset should be considered in the choice of
      treatment.

PMID- 20131533
TI  - APACHE II, POSSUM, and ASA scores and the risk of perioperative complications in
      patients with colorectal disease.
AB  - OBJECTIVE: This study was designed to assess the role of the ASA, POSSUM and
      APACHE II score systems for predicting the complications in patients undergoing
      surgery for colorectal diseases. METHODS: We retrospectively analyzed 539
      patients undergoing colorectal surgery between January 1996 and December 2006.
      The accuracy of ASA, POSSUM and APACHE II score systems for predicting
      perioperative complications has been analysed. RESULTS: Total postoperative
      morbidity was 15%, overall perioperative mortality was 1.5%. APACHE II and POSSUM
      predicted with the same accuracy the perioperative complications (0.65 and 0.68,
      respectively), while ASA score system revealed a poorer predicting accuracy
      (0.56). POSSUM predicted death rate more accurately compared to the APACHE II
      classification (1.6% vs. 10.4%). CONCLUSIONS: APACHE II and POSSUM score systems
      may be useful tools helping surgeons to identify patient groups at high risk for
      complications. The ASA classification resulted less accurate, probably because
      related to the anesthesiologist's knowledge.

PMID- 20131534
TI  - Mesh versus direct suture for the repair of umbilical and epigastric hernias. Ten
      year experience.
AB  - BACKGROUND: The objective of this study was to evaluate outcomes of mesh versus
      primary suture procedures for repair of anterior abdominal wall midline hernias.
      RESULTS: Between 1995 and 2005, 98 patients (46 males) underwent repair of
      umbilical (69 cases) or epigastric (29 cases) hernias. Primary suture of the
      defect was performed in 34 cases (group 1). A polypropylene mesh was positioned
      in 64 cases (group 2). Overall, mean aponeurotic defect diameter was 2.5 cm
      (range 0.5 +/- 10 cm). Procedures were carried out under local anesthesia in 76
      instances (71% group 1 vs. 81% group 2). Complications occurring in group 2
      comprised three seromas, one hematoma and one prosthetic infection. Follow up was
      scheduled yearly up to the fifth postoperative year. Recurrence rate in group 1
      was 14.7% compared to 3.1% in group 2 (logrank test p 0.0475). CONCLUSIONS:
      Anterior preperitoneal mesh repair of abdominal wall midline hernias under local
      anesthesia seems to be a safe and effective technique that can be performed as a
      day surgery procedure. A slightly increased risk of postoperative local
      complications following mesh repair is offset by a reduced rate of recurrence in
      comparison to suture repair.

PMID- 20131535
TI  - Necrotizing fasciitis in childhood. Case report, and review of the literature.
AB  - INTRODUCTION: Necrotizing fasciitis (NF) is an aggressive and relatively rare
      soft tissue infection, involving the fascia and the subcutaneous tissue, with a
      rapidly fatal evolution. CASE REPORT: GE, an 8 year-old girl presented with edema
      and redness of the external genitalia. Twelve hours later, she became toxic while
      her redness extended in the abdominal wall and both upper thighs. CT of the
      abdomen was consistent with NF. She underwent prompt surgery (debridement and
      colostomy), followed by plastic reconstruction. CONCLUSION: Early suspicion and
      prompt aggressive surgery is the key of therapy in case of NF.

PMID- 20131536
TI  - [Functional sequelae after low anterior rectal surgery].
AB  - INTRODUCTION: The treatment of colorectal cancer has changed radically in the
      last decades. Due to the great advances it is now often possible to subject
      patients to oncological radical treatments without applying to highly aggressive
      surgery, such as the Miles abdomino perineal resection, which requires a
      definitive colostomy. So nowadays we more and more apply to anterior resection of
      the rectum. Some recent studies about quality of life in patients who underwent
      anterior resection of the rectum focalized their attention on postoperative
      functional sequels. In particular incontinence, constipation, obstructed
      defecation and urgency are some of the symptoms which define the anterior
      resection syndrome, which can be efficiently treated by electrostimulation and
      biofeedback. MATERIALS AND METHODS: A prospective study on 61 patients who
      underwent between 2002 and 2007 anterior resection of the rectum with total
      mesorectal excision for adenocarcinoma, has shown symptoms of anterior resection
      syndrome in 14 patients. Succeeding treatment with sphincter electrostimulation
      and biofeedback has shown improvement in all patients and complete resolution of
      the anterior resection syndrome in 10 patients who showed a great compliance and
      a steady improvement on quality of life. DISCUSSION AND CONCLUSIONS:
      Rehabilitative treatment with electrostimulation and biofeedback can sensibly
      reduce symptoms of anterior resection syndrome. An accurate manometric functional
      assessment is necessary before starting treatment with electrostimulation and
      biofeedback.

PMID- 20131537
TI  - [Ligasure haemorrhoidectomy. Personal experience].
AB  - INTRODUCTION: It has been estimated that 58% of people over 40 years of age have
      haemorrhoidal disease to some extent. Indications for operative treatment include
      third and fourth degree prolapsing haemorrhoids. Haemorrhoidectomy is frequently
      associated with significant postoperative pain and new techniques to reduce this
      pain are constantly under evaluation. The present study was conducted to
      determine the usefulness of the Ligasure system and compare it with conventional
      diathermy for haemorrhoidectomy. METHODS: 25 patients with grade 3 or 4
      haemorrhoids requiring surgery were recruited and submitted to Ligasure
      Haemorrhoidectomy. They were compared with 25 patients operated with Milligan
      Morgan technique with diathermy. All patients were operated by the same two
      surgeons, who collaborate each other. RESULTS: There were no statistical
      differences in age, gender or clinical symptoms between the two groups. The mean
      operating time was 21.1 minutes (range, 15-32 min) in the Study Group and 19.8
      min (range, 15-28 min) in the Control Group. Patients were dismissed the same day
      or the following day after surgery, without statistical differences. Early
      complications were similar, mainly represented by urinary retention, while late
      complications were comparable (1 bleeding in each group and 2 late healing in the
      Control Group). A partial reduction in postoperative pain and a faster healing of
      postoperative scars were observed in the Study Group. CONCLUSIONS: Ligasure
      Haemorrhoidectomy is a safe procedure in the treatment of 3rd and 4th grade
      haemorrhoids. In our study we observed a reduction of postoperative oedema and a
      faster healing of surgical scars, without affecting postoperative complications.

PMID- 20131538
TI  - [The Poland' syndrome. Case report].
AB  - A case of Poland's syndrome in a 2-year-old female is described. The patient had
      come to our Emergency department for abdominal pain. The thorax's asymmetric
      depression and the brachysyndactyly of the right hand are fundamental elements to
      make Poland's syndrome diagnosis in our patient. In this report, the different
      formes of Poland's syndrome, the classification and the indications for a
      surgical intervention are described. Besides the importance of a precocious
      diagnosis is underlined, due to avoid complications related to late
      rehabilitation and multidisciplinary approach to the patient.

PMID- 20131539
TI  - [Colorectal cancer: tissutal explantation and primary cell culture].
AB  - BACKGROUND: Setting of cellular cultures extracted from colorectal cancer tissue
      represents a valid model for in vitro study of biological and molecular
      characteristics of each single tumor finalized to obtain a tailored
      chemiotherapy. The end point of this study is to create primary cellular cultures
      from "fresh" cancer tissue in different stages of evolution. METHODS: Cancer
      tissue samples are obtained by means of surgical excisional biopsy or by means of
      semi-automatic biopsy instrument (Sprig-Cut). After having compared different
      approaches, two experimental protocols have been selected to have the highest
      number or intact cells: enzimatic digestion with trypsin and explantation.
      RESULTS AND CONCLUSIONS: Primary cell culture free of microbic contamination,
      obtained mainly by means of Spring-Cut methods, underwent immunohistochemical
      analysis to evaluate what kind of cell have been grown in vitro by measuring the
      expression of CK20 and GFAP both resulted positive. The possibility of setting a
      primary cell culture which represents the cancer of each patient allows a
      pharmacologic and biomolecular study which can contribute to the development of a
      tailored adjuvant therapy with many advantages for the patient in terms of
      positive answer to the treatment and reduced toxicity.

PMID- 20131540
TI  - Remote cerebellar haematoma after lumbar disc surgery. Case report.
AB  - Remote cerebellar haematoma (RCH) from the operative site is one of the most
      serious, although extremely rare, complications of spinal surgery. Dural opening
      is common to every reported case of a spinal procedure complicated by cerebellar
      hemorrhage, supporting the hypothesis that CSF loss is central to the
      pathogenesis of this condition. We report our experience with the case of
      cerebellar haematoma after lumbar disc surgery and the literature is reviewed.

PMID- 20131541
TI  - An unusual case of acute unilateral parotitis following abdominal surgery. Report
      of a case and review of the literature.
AB  - BACKGROUND: Postoperative parotitis is a well known entity which can develop in
      patients who undergo major abdominal surgery. METHODS: We present a case of
      postoperative parotitis which occurred after a laparotomy for incisional hernia
      repair. RESULTS: After establishing diagnosis by ultrasonography assessment and
      blood chemical tests, patient was successfully treated by morphine discontinuing
      and antibiotics therapy. CONCLUSION: Beside sialolithiasis, sitting position or
      dehydratation we suggest that morphine could play a substantial role in the
      development of postoperative parotitis.

PMID- 20131542
TI  - [Acute acalculous cholecystectoctomy associated with haemobilia in
      polytraumatized subject. Case report].
AB  - The Authors report the clinical case of polytraumatized patient who has colic
      abdominal pain and Murphy sign after 68 days from damaging event. This
      symptomatology is consequent to Acute Acalculous Cholecystitis (ACC) associated
      with hemobilia. This work may be different because hemobilia in polytraumatized
      patient, like causal factor of acute cholecystitis, is an isolated case in
      literature. The Authors discuss on ACC risk factors, diagnosis and therapy.

PMID- 20131543
TI  - [The conservative treatment in the splenic trauma].
AB  - The Authors mention the historical evolution that led to consider the splenectomy
      as the ideal operation in patients with post-traumatic lesions of the spleen.
      They linger then on the actual knowledges about the pathophysiology of this organ
      that determined a substantial change of mind toward a conservative treatment,
      when possible, reporting data from the literature. In haemodynamically stable
      patients with splenic trauma, conservative treatment is recommended to preserve
      the spleen and prevent potentially lethal post-splenectomy infectious
      complications. A personal observation of a 17-years-old boy who suffered splenic
      hematoma after a trauma is referred. The decision to adopt a non-operative
      strategy allowed the preservation of the spleen without complications. Every
      therapeutic choice must be consequent to an accurate clinical evaluation of the
      single patient, either it suggests a surgical abdomen's exploration in urgency or
      the monitoring of the patient. This curative strategy is supported by the
      considerable contribution offered by sophisticated methods of radiological
      imaging and by the commercialization of substances with an high sticking power.
      Laparoscopic management of spleen trauma can be used once a positive diagnosis
      has been made. It is useful for assessing the degree of splenic injury. It is an
      effective procedure for the evaluation and treatment of haemodynamic stable
      patients with splenic injuries for whom non operative treatment is controversial.
      In conclusion conservative procedure for splenic lesions must find a growing
      consent, but warning against a too large widening of the indications for the
      conservative treatment beyond true safety conditions.

PMID- 20131544
TI  - [How is general surgery changing in Italy?].

PMID- 20131545
TI  - [Negative and positive prognostic factors in polytrauma, especially referring to
      "golden hour"].
AB  - BACKGROUND AND OBJECTIVES: Polytrauma, or the condition of victim affected by two
      or more lesions compromising vital parameters, is the third cause of death
      (0.6/l1000/year), and the first one of mortality for subjects 44 year-younger,
      responsible of 26000 annual deaths, (60% for car accidents). MATERIALS AND
      METHODS: A personal experience concerning four car crash victims contemporary
      accepted in our Surgical Emergency of a peripheric hospital and an overview of
      clinical and therapeutical aspects of polytrauma are reported. RESULTS:
      Topographic distribution of deaths shows this patterns: during the transport to
      hospital: 4%; peripheric hospital: 10%; Emergency Departments: 13%; during
      hospitalization: 25%; Intensive Care Units: 46%. The outcome is strictly
      depending on the quality of the first approach, confirming the importance of
      golden hour. CONCLUSIONS: The complexity of polytrauma is related to the various
      pathologies affecting the victims, either neurological ones, or thoracic,
      abdominal, vascular and orthopedic ones, emphasizing the role of diagnostic and
      therapeutic timely approach.

PMID- 20131546
TI  - Multimodal treatment for oesophageal primary cancer. A preliminary study.
AB  - OBJECTIVE: This study examines the role of chemoradiotherapy, surgical
      reconstructive techniques of the esophagus and lymphadenectomy in relation to
      morbidity and mortality. METHODS. From January 2005 to January 2008 we observed
      18 patients with esophagus cancer. Eleven patients manifested a lesion of the
      middle third, 4 patients had a lesion of the upper third and 3 patients had a
      lesion of the lower third. Preoperative histological evaluation revealed 3
      adenocarcinomas and 15 squamous carcinomas. Four patients with a lesion of the
      upper third received neoadjuvant chemotherapy RESULTS: In 13 patients
      reconstruction used stomach and 5 patients underwent reconstruction with the
      colon. Complications ensued in 3 of the latter: dehiscence of the anastomosis,
      anastomotic stenosis and chylothorax. Three patients highlighted a moderate
      malabsorption syndrome. A T3N1M0 patient received postoperative cisplatin/5
      fluorouracil and radiation therapy. CONCLUSIONS: The use of the stomach
      represents the therapeutic gold standard for minimized incidence of
      complications. Lymphadenectomy allows to establish a precise stage of cancer.
      Chemoradiotherapy is recommended in case of risk of relapse.

PMID- 20131547
TI  - [Diagnosis, surgical treatment and follow-up of the hyalizing trabecular adenoma
      of the thyroid].
AB  - In the last twenty years, we submitted 853 patients to thyroid surgery. We found
      only in ten patients a hyalinizing trabecular adenoma at the (histological
      control), as a confirmation of the rarity of this tumour. The authors report a
      retrospective analysis of this cases to document the clinical features and the
      evolution through a long term follow-up that has showed no recurrent disease. In
      conclusion the hyalinizing trabecular adenoma represents a low malignant
      potential tumour. However, the uncertain clinical behaviour doesn't be
      undervalued and patients must be subjected to accurate follow-up.

PMID- 20131548
TI  - Diagnostic evaluation prior to cholecystectomy in mild-moderate acute biliary
      pancreatitis.
AB  - OBJECTIVES: The importance of papillary obstruction in the pathogenesis of acute
      biliary pancreatitis (ABP) is widely recognized. The aim of this study was to
      evaluate the usefulness of the MRCP before the VLC in the patients with mild
      acute biliary pancreatitis. METHODS: In the period 2003-2008, 47 patients were
      submitted to a MRCP (F/M: 28/19) with mild ABP without increase of the
      cholestasis tests and absence of choledocholithiasis at the abdominal US. During
      a follow up from 30 to 60 days after the VLC, the presence of jaundice or relapse
      of ABP were evaluated in all patients. RESULTS: Thirteen patients had diagnosis
      of choledocholithiasis at the MRCP and they were submitted to an ERCP endoscopic
      sphincterotomy and stones removal; 34 patients with a negative MRCP were
      submitted to the VLC. Among these, on 10th postoperative days, one patient has
      had recurrent ABP, and was submitted to ERCP/ES. All the 47 patients submitted to
      the MRCP before the VLC did not have jaundice or relapse of the ABP during the
      follow-up period. CONCLUSION: The MRCP was an accurate investigation for the
      preoperatory diagnosis of choledocholithiasis; even if it is not possible to
      recommend its utilization extensively, it is an important procedure for the
      patients with diagnosis of mild ABP to select all those to submit to the ERCP.

PMID- 20131549
TI  - [Abdominal compartment syndrome (ACS) after abdominal aortic aneurysm (AAA) open
      repair].
AB  - INTRODUCTION: The Abdominal Compartment Syndrome (ACS) is a "condition in which
      increased tissue pressure in a confined anatomic space, causes decreased blood
      flow leading to ischaemia and organic dysfunction and may lead to permanent
      impairment of function". MATERIALS AND METHODS: Between June 2007 and June 2008
      all patients recovered to our Institution for Abdominal Aortic Aneurysm (AAA)
      underwent intermittent intra-abdominal pressure monitoring using intra-vescical
      catheter. Pressure data were registered before abdominal incision, during
      intervention, at closure of abdominal wall and at 6, 12, 24 and 36 hours in post
      operative course. Rise in Intra-Abdominal Pressure (IAP) more then 20 mmHg was
      considered for surgical decompression. RESULTS: Twenty three cases of AAA were
      treated surgically Fourteen underwent elective repair and 9 emergency/urgency
      repair; in the emergency/urgency group, 8 were symptomatic without rupture signs
      and one case presented TC rupture signs. In the last case we registered
      preoperatively IAP more than 20 mmHg treated with only skin tension-free suture.
      No perioperative mortality was registered. DISCUSSION: ACS have been increasingly
      recognized as causes of significant morbidity and mortality over the last years
      after AAA surgery. ACS was recently classified from the World Society of the
      Abdominal Compartment Syndrome (WSACS) as primary, secondary and recurrent. ACS
      was recognized as major prognostic factor after AAA repair. ACS incidence ranges
      from 4 to 12%. Even if ACS etiological bases are not well known, principal risk
      factor for ACS development after AAA repair are massive fluid resuscitation
      infusion and aortic clamping IAP values, and subsequent possibility of ACS
      development, are superior after ruptured AAA repair than elective repair. Also in
      our study, even if limited by small number of cases, we registered differences in
      IAP value during emergency/urgency repair and elective repair. Patients
      management with rising IAR or at risk of ACS development, should be mandatory
      decompressed for IAP higher than 20 mmHg or also with inferior values if in
      association to organ dysfunction. IAP measurement can be performed directly or
      indirectly and all these techniques have as objective IAP monitoring before its
      clinical manifestation in ACS. CONCLUSION: ACS can be considered a reliable
      predictive factor for aneurysm surgery outcome. Prevention of the ACS, with early
      recognition of rising IAP and urgent intervention to decompress the tense abdomen
      can lead to mortality reduction after aneurysm repair. The measurement of IAP is
      simple and non-invasive, and should be a routine component of physiological
      monitoring in patients following ruptured aneurysm repair in association with
      hypotensive hemostasis.

PMID- 20131550
TI  - [New trends in the treatment of venous leg ulcer. Personal experience].
AB  - Venous leg ulcer is the most frequent cause of trophic lesions of the limbs in
      patients with chronic venous insufficiency. Appropriate management of cutaneous
      vascular lesions is based on systemic, vascular and local assessment. The Authors
      used a protease-modulating matrix in 126 patients suffering from venous leg
      ulcers with wound granulation: 81 (64.2%) patients with primary chronic reflux
      disorder and varicose veins and 45 (35.8%) post-thrombotic; in addition 30
      patients (23.8%) had peripheral arteriopaty and 41 (32.5%) peripheral arteriopaty
      and diabetes. One hundred sixteen patients showed complete healing, 2 were
      refractory to every treatment and 8, with arteriopathy and diabetes, are on the
      mend. According to the literature we achieved reduction of the healing time and
      increased healing rate. All patients were treated in outpatient settings. In
      conclusion the Authors suggest protease-modulating matrix is a really effective
      treatment of venous leg ulcers with wound granulation. Their treatment is also
      feasible in outpatient treatment with a reduction in health spending and reduced
      absence from work.

PMID- 20131551
TI  - Comparison of topical glyceryl trinitrate with diltiazem ointment for treatment
      of chronic anal fissure. A randomized clinical trial.
AB  - BACKGROUND: The aim of this study was to compare the effect of topical glycerol
      trinitrate ointment (GTN) with topical diltiazem hydrochloride ointment (DTZ) in
      the treatment of chronic anal fissure. METHOD: Prospectively, 102 patients were
      treated randomly with either GTN ointment (0.2%) or DTZ ointment (2%) couple of
      times daily for 12 weeks. RESULTS: Forty-five patients (88.2%) in group DTZ and
      36 patients (70.6%) in group GTZ had reduction of symptoms. The decrease in the
      symptoms for group DTZ were significantly more than that for group GTN (P =
      0.02). Mean time of symptom reduction was 2.44 +/- 0.30 in group DTZ and 2.50 +/-
      0.28 weeks in group GTN without significant differences between two groups (P >
      0.05). Complete relieving of symptoms was observed in 72.5%, 54.9% patients in
      groups DTZ and GTN, respectively. The frequency of complete relieving of symptoms
      between two groups was not significant (P > 0.05). Complete remission of anal
      fissure was occurred in 66.7% patients in group DTZ and 54.9% patients in group
      GTN, which was no different, significantly. Mean time taken for fissure healing
      in GTN group was dramatically less than DTZ group (P = 0.001). Finally, 33.3% of
      patients in DTZ group and 45.1% of patients in GTN group was operated. The need
      for operation was not significant between two groups (P > 0.05). CONCLUSION: Both
      DTZ and GTN are equally effective and can be the preferred first-line treatment
      of chronic anal fissure a. However, GTN is associated with a higher rate of
      headache, and it should be replaced by DTZ.

PMID- 20131552
TI  - An uncommon cause of pulsation on the left side of the thorax. Case report.
AB  - A 70-year-old man affected by clinical findings of congestive heart failure eight
      months after aneurysmectomy of a true left ventricular aneurysm, presented with
      actual pseudoaneurysm of the left ventricle. There was a 5 x 5 cm soft tissue
      mass on the left side of the chest, synchronously pulsating with heart beating.
      The repair was performed with the aid of cardiopulmonary bypass. Myocardial
      tissues were approximated and closed by using two Teflon stripes. BioGlue was
      applied on the sutures and between the stripes. Although there is a significantly
      high mortality of the pseudoaneurysm cases their repair can and should be
      performed in an urgent procedure.

PMID- 20131553
TI  - [Ectopic breast tissue and a carcinoma in atypical positions].
AB  - AIM: The aim of the study was to considerate neoplams of ectopic breast tissue in
      particular concerning the diagnostic and surgical related problems, analysing our
      experience in this extremely rare pathology. MATERIALS AND METHODS: A group of
      five women affected by neoplasm of ectopic breast tissuehave been examinated,
      four of them in axillary breast tissue and the other one in parasternal area.
      They came to our clinical observation (UOC BCG 21, UOC BCG 27-Policlinico Umberto
      I,-Universita "Sapienza" di Roma) between 2006 and 2008. All the patient
      underwent surgical intervention in our department. DISCUSSION: According to the
      literature we can assess that this is a rare pathology and so the diagnostic and
      surgical choices are different from case to case depending on the size, the
      localization , the local invasion. CONCLUSIONS: This rare pathology can occur in
      many different forms and areas. This fact makes impossible to create a guideline
      of diagnosis and treatment. This one must be acted in respect of radicality and
      when it is possible, of aesthetic criteria.

PMID- 20131554
TI  - [Pelvic splenomegaly. Ptosic, migrant or accessory spleen?].
AB  - A wandering or ectopic spleen is a rare condition in which the spleen is not
      located in the left upper quadrant but is found lower in the abdomen or in the
      pelvic region caused by improper fixation of the ligamentous attachments. Laxity
      of the peritoneal attachments of the spleen results in splenic hyper mobility,
      known as wandering spleen. Congenital and acquired causes have been advocated to
      explain its onset. However, the precise aetiology is not completely understood.
      Many patients with wandering spleen are asymptomatic and therefore, the real
      incidence is unknown. Symptomatic patients may have intermittent abdominal pain
      because of splenic congestion with intermittent torsion of the splenic pedicle
      and its spontaneous detorsion, or may present acutely with pedicle torsion with
      subsequent infarction. Pain and dangerous potential evolution recommend surgery,
      splenoplexy or splenectomy. The Authors report the case of a 48-year-old man with
      painful abdominal mass suspected for wandering splenomegaly after diagnostic
      imaging (abdominal Ultrasonography and TC). Laparotomy evidenced a large spleen
      (DL 22 cm.) with a long (1 mt) and tortuous vascular pedicle, both removed.
      Histopathologic examination showed partial infarction of the spleen. The
      postoperative course was uneventful.

PMID- 20131555
TI  - Boerhaave's syndrome: long free interval before successful primary repair. Case
      report.
AB  - AIM: Report case of a 66-year-old man come to our observation for a bilateral
      pleural effusion, ten days after clinical manifestations of chest pain, initially
      misdiagnosed with a myocardial infarction. MATERIAL OF STUDY: On the same day,
      the patient underwent an emergency chest CT scan with orally administered
      contrast medium that confirmed our suspicion of breakage of the esophageal wall.
      The patient underwent to a left thoracotomy: the visceral pleura and all the
      structures covered by the parietal pleura were affected by a widespread necrotic
      process. The subsequent cleansing of the pleural cavity revealed that the distal
      portion of the thoracic esophagus was lacerated for about 5 cm; the tear was
      repaired with continuous reabsorbable sutures; to protect the suture
      fundoplication of the gastric fundus was performed. RESULTS: Post-operative
      course was complicated on 15th day by a chylous spreading from the chest drains;
      to complete the postoperative checks, a chest CT scan was therefore performed,
      orally administering the contrast medium without any signs of extraluminal
      spreading; the chylous effusion resolved spontaneously with diet. After being
      discharged, the patient was followed on an outpatient basis for 36 months.
      CONCLUSION: Boerhaave's syndrome is a rare and serious clinical condition; when a
      patient is diagnosed after 24-48 hs, many surgeons follow conservative treatment;
      however primary repair can be safely accomplished regardless of the time interval
      between perforation and operation, like our singular experience demonstrated

PMID- 20131556
TI  - Post cholecystectomy syndrome: an out of date topic?
AB  - The post-cholecystectomy syndrome, whose finding is always possible, apart of
      cases of biliary tract iatrogenic injuries (stenosis or leakages), is related to
      a residual cystic stump lithiasis or more often related to a synchronous main
      bile duct disease (lithiasis and/or oddities) that could be prevented by pre- or
      intra-operative cholangiography. The clinical suspect of those conditions should
      be confirmed by cholangio-MRI. The treatment of main bile duct lithiasic disease
      is essentially endoscopical. The treatment of the remnant stump lithiasis
      flogosis could be performed by laparoscopic or more often by laparotomic surgery
      because of post-operative flogistic adhesions, especially if an open
      cholecystectomy has been already performed.

PMID- 20131557
TI  - [Malignant degeneration of chronic pilonidal cyst. Case report].
AB  - This report describes the case of a patient with a chronic pilonidal cyst
      developed squamous cell carcinoma. The case was treated with primary radical
      excision, followed adjuvant radiation and chemiotherapy. Recurrence following
      such treatment was high and prognosis poor compared with non melanoma skin
      cancer.

PMID- 20131558
TI  - [S. Camillo de Lellis Hospital of Rome].

PMID- 20131559
TI  - Online publication and the impact factor.

PMID- 20131560
TI  - Evaluation of social interaction during occupational engagement.
AB  - The Evaluation of Social Interaction (ESI; Fisher & Griswold, 2008) assesses a
      person's performance of social interaction skills in the natural context with
      typical social partners during any area of occupation. We used Rasch analysis of
      175 observations of 128 people, ages 4-73, to examine internal scale validity,
      the items' skill hierarchy and intended purpose, and the ESI's ability to
      differentiate between people with and without disabilities. The ESI demonstrated
      validity for 24 of 27 skills and six intended purposes, with a hierarchy of
      performance. Of the observations, 95.3% demonstrated goodness of fit to the Rasch
      model, indicating person response validity. People without a disability
      demonstrated significantly higher social skills performance than those with a
      known disability (t= 4.468, df= 83 p= .000). The ESI has the potential to provide
      a quantitative assessment of social interaction performance in the natural
      context of a person's desired occupation and may be useful for intervention
      planning and outcome measurement.

PMID- 20131561
TI  - Effect of assistive technology in a public school setting.
AB  - The Individuals With Disabilities Education Improvement Act of 2004 (IDEA)
      requires assistive technology (AT) be considered at the yearly individualized
      education program (IEP) meeting of every student in special education. IDEA also
      directs that AT be implemented on the basis of peer-reviewed literature despite a
      paucity of research on AT's effectiveness in the public schools. This repeated
      measures quasi-experimental study explored AT's effect in a public school special
      education setting. Participants (N=13) were a heterogeneous group of students in
      1 school system who had newly provided AT to address academic and communication
      goals in one school year. Results suggest that relative to other interventions,
      AT provided by a multidisciplinary team may have a significant effect on IEP goal
      improvement (t[12] = 5.54, p= .00) for students in special education (F[2] =
      9.35, p= .00), which may support AT's use in special education by occupational
      therapists as directed by IDEA.

PMID- 20131562
TI  - The Log Handwriting Program improved children's writing legibility: a pretest
      posttest study.
AB  - OBJECTIVE: We determined the feasibility and outcomes of the Log Handwriting
      Program (Raynal, 1990), an 8-week training program based on task-specific
      practice of handwriting. METHOD: We used a pretest-posttest design involving 16
      first- and second-grade Australian students. Handwriting training sessions
      occurred in schools for 45 min per week over 8 weeks, in groups of 2 or 3. Weekly
      homework was provided. The primary outcome measure was the Minnesota Handwriting
      Assessment (range = 0 to 34; Reisman, 1999). Legibility, form, alignment, size,
      spacing, and speed were measured. RESULTS: All six assessment subscales showed
      statistically significant differences. Legibility improved by a mean of 4.1
      points (95% confidence interval = 2.5 to 5.7); form, 5.3 points; alignment, 7.8
      points; size, 7.9 points; and space, 5.3 points. Speed decreased by 3.9 points.
      CONCLUSION: Preliminary evidence indicates that an 8-week Log Handwriting Program
      is feasible and improved handwriting in primary school children.

PMID- 20131563
TI  - Reliability and validity of the Evaluation Tool of Children's Handwriting-Cursive
      (ETCH-C) using the general scoring criteria.
AB  - OBJECTIVES: To determine the reliability and aspects of validity of the
      Evaluation Tool of Children's Handwriting-Cursive (ETCH-C; Amundson, 1995), using
      the general scoring criteria, when assessing children who use alternative writing
      scripts. METHOD: Children in Years 5 and 6 with handwriting problems and a group
      of matched control participants from their respective classrooms were assessed
      with the ETCH-C twice, 4 weeks apart. RESULTS: Total Letter scores were most
      reliable; more variability should be expected for Total Word scores. Total
      Numeral scores showed unacceptable reliability levels and are not recommended. We
      found good discriminant validity for Letter and Word scores and established
      cutoff scores to distinguish children with and without handwriting dysfunction
      (Total Letter <90%, Total Word <85%). CONCLUSION: The ETCH-C, using the general
      scoring criteria, is a reliable and valid test of handwriting for children using
      alternative scripts.

PMID- 20131564
TI  - Development and standardization of a "do-eat" activity of daily living
      performance test for children.
AB  - BACKGROUND: The Do-Eat was developed to evaluate daily task performance abilities
      among children with developmental coordination disorder (DCD). This study
      investigated the tool's reliability and validity. METHOD: Participants were 59
      children ages 5 to 6.5 years; 30 children diagnosed with DCD according to the DSM
      IV-TR; and a control group of 29 children, who were matched for age, gender, and
      sociodemographic background. RESULTS: Both the Do-Eat and the accompanying Parent
      Questionnaire yielded high internal consistency (alpha s = .89-.93). Construct
      validity was demonstrated by significant between-group differences on the Do-Eat
      (t[57] = 14.09, p<.001) and the Parent Questionnaire (t[57] = 3.64, p<.001).
      Significant correlations between children's scores on the sensory-motor component
      of the Do-Eat and the Movement Assessment Battery for Children final score
      confirmed concurrent validity (r = -.86, p<.001). CONCLUSIONS: Results suggest
      that the Do-Eat is a reliable, valid tool for identifying children at risk for
      DCD.

PMID- 20131565
TI  - Randomized controlled trial of the Breast Cancer Recovery Program for women with
      breast cancer-related lymphedema.
AB  - Evidence-based exercise and relaxation recommendations for people with breast
      cancer-related lymphedema (BCRL) are needed. We report a randomized controlled
      study of one program, designed to achieve synergistic improvements in physical
      and emotional BCRL symptoms. People in the treatment group received an exercise
      and relaxation program, The Breast Cancer Recovery Program (N=16). The control
      participants (N=16) continued with health professionals' recommendations.
      Participants were tested at entry, 2.5 weeks, 5 weeks, and 3 months. Treatment
      group participants, compared with control participants, demonstrated significant
      treatment effects for improved bioimpedance z, arm flexibility, quality of life,
      mood at 3 months, and weight loss. Adherence was high for this safe and effective
      program, which improved lymphedema physical and emotional symptoms.

PMID- 20131566
TI  - Telerehabilitation and electrical stimulation: an occupation-based, client
      centered stroke intervention.
AB  - OBJECTIVE: We examined the efficacy of a remotely based arm rehabilitation
      regimen. A 62-year-old man participated in occupation-based, task-specific
      practice of activities of daily living (ADLs) >3 years after stroke. The entire
      regimen was administered over the Internet using personal computer-based cameras
      and free network meeting software. METHOD: Fugl-Meyer Assessment (FM), Action
      Research Arm Test (ARA), and Canadian Occupational Performance Measure (COPM)
      were administered before intervention. One week after treatment, FM, ARA, and
      COPM were readministered. RESULTS: The participant exhibited reduced impairment
      and reduced functional limitation. He also expressed enhanced satisfaction with
      his ability to perform ADLs and rated his ADL performance better after
      intervention. The participant could now drive using both hands, use eating
      utensils, and catch and throw a ball. CONCLUSION: Data suggest feasibility and
      efficacy of a remotely based, inexpensive approach using functional electrical
      stimulation for affected arm rehabilitation after stroke.

PMID- 20131567
TI  - Documenting progress: hand therapy treatment shift from biomechanical to
      occupational adaptation.
AB  - The investment of time and self to develop therapeutic relationships with clients
      appears incongruent with today's time-constrained health care system, yet
      bridging the gap of these incongruencies is the challenge therapists face to
      provide high-quality, client-centered, occupation-based treatment. This case
      report illustrates a shift in approach from biomechanical to occupational
      adaptation (OA) in an orthopedic outpatient clinic. The progress of a client with
      lupus-related arthritis who was 6 days postsurgery is documented. The
      intervention initially used a biomechanical frame of reference, but when little
      progress had been made at 10 weeks after surgery, a shift was made to the more
      client-centered OA approach. The Canadian Occupational Performance Measure was
      administered, and an OA approach was initiated. On reassessment, clinically
      important improvements were documented in all functional tasks addressed. An OA
      approach provides the bridge between the application of clinical expertise,
      client-centered, occupation-based therapy and the time constraints placed by
      payer sources.

PMID- 20131568
TI  - Influence of age and bolus size on swallowing function: basic data and assessment
      method for care and preventive rehabilitation.
AB  - Objective numerical data on swallowing function are needed to aid in eating and
      swallowing intervention and preventive rehabilitation. Using noninvasive methods,
      the influences of age and differences in size of water bolus on laryngeal
      activity and respiratory activity were examined in healthy young and older women.
      Swallowing function was influenced by age and bolus size. Influence of bolus size
      was recognized only in duration of laryngeal movement in younger women, with no
      apparent influence in older women. Results for older women were thought to be
      related to declines in swallowing function with the physiological aging of
      respiratory and swallowing muscles. In the future, noninvasive methods need to be
      developed for evaluating function and therapeutic effects against swallowing
      function impairment and to provide objective numerical data for health insurers.

PMID- 20131569
TI  - Grasping naturally versus grasping with a reacher in people without disability:
      motor control and muscle activation differences.
AB  - OBJECTIVE: We investigated motor control and muscle activation when reaching for
      and grasping objects with a reacher compared with the unaided hand. METHOD: In a
      repeated-measures counterbalanced design, 41 healthy participants with no
      previous experience using a reacher were randomly assigned to a sequence of four
      conditions. Movements of the wrist and fingers were recorded using a three
      dimensional Qualisys camera system for assessing reach and grasp. Muscle
      activations from finger and arm flexors and extensors were recorded by surface
      electromyography. RESULTS: Participants exhibited a smaller grasp aperture,
      longer reaching time, and more muscle activity when they used a reacher.
      CONCLUSION: Efficient motor control, which requires both time and practice, is
      needed to successfully use a reacher. Clients presented with reachers without
      sufficient time to develop motor skills unique to reacher use may be more likely
      to abandon this assistive device and fail to benefit from its function.

PMID- 20131570
TI  - Near-vision acuity levels and performance on neuropsychological assessments used
      in occupational therapy.
AB  - We investigated how induced blur affects performance on the Trail Making Test and
      Digit Symbol Test routinely used in occupational therapy cognitive evaluations.
      The study used a factorial design with both age (young and old adults) and
      simulated blur levels of near visual acuity (20/50 and 20/100) manipulated
      between participants. A sample of 124 healthy, community-living adults was used
      in the final analysis. Significant differences (p<.05) were found in performance
      for young participants between 20/50 and 20/100 blur level as well as between
      20/20 and 20/100 blur level for the Digit Symbol Test. Scores for old
      participants decreased as a function of blur but were not significant. This study
      illustrates that cognitive evaluations used throughout the lifespan may require
      the appropriate visual acuity level to maximize performance. Occupational
      therapists' understanding of client factors and their effect on performance is
      fundamental to the client evaluation process.

PMID- 20131571
TI  - Establishing criterion validity of the Useful Field of View assessment and Stroke
      Drivers' Screening Assessment: comparison to the result of on-road assessment.
AB  - OBJECTIVES: We sought to determine the criterion validity of the Useful Field of
      View (UFOV) assessment and Stroke Drivers' Screening Assessment (SDSA) through
      comparison to the results of on-road assessment. METHOD: This was a prospective
      study with people with stroke. Outcome measures used were UFOV, SDSA, and the
      results of on-road assessment. RESULTS: Both the results on UFOV (Divided
      Attention subtest, p<.01; Selective Attention subtest, p<.05) and SDSA (p<.05)
      were significantly related to the recommendation from on-road assessment. The
      Divided Attention subtest of the UFOV had the highest sensitivity value (88.9%).
      CONCLUSIONS: UFOV and SDSA are valid assessments of driving ability for stroke.
      The Divided Attention subtest of the UFOV can guide decision making of
      occupational therapists in stroke driver rehabilitation and in determining those
      who require further assessment on road because they pose a safety risk. Screening
      assists people with stroke to decide whether they are ready to have an on-road
      assessment.

PMID- 20131572
TI  - Relationship between handwriting and keyboarding performance among fast and slow
      adult keyboarders.
AB  - OBJECTIVE: We examined the relationship between handwriting and keyboarding
      performance and between these writing modes and underlying performance skills.
      METHOD: Sixty-three young, healthy adults who used the computer daily were
      recruited for this study by means of a convenience sample (mean = 25.3, standard
      deviation = 3.0); 15 were slow keyboarders and 17 were fast keyboarders.
      Participants were administered handwriting and keyboarding assessments, as well
      as measures of finger function, kinesthetic processing, and eye movement.
      RESULTS: Although handwriting and keyboarding speed were moderately correlated,
      these activities did not share underlying performance skills. In addition,
      different correlation patterns between written communication modes and
      performance skills were found among slow and fast keyboarders. CONCLUSION:
      Results suggest that occupational therapists and educators should consider a
      variety of factors before recommending keyboarding as an alternative written
      communication method for people with handwriting difficulties. Moreover,
      different recommendations appear to be warranted for slow and fast keyboarders.

PMID- 20131573
TI  - Reconstructing meaning through occupation after the death of a family member:
      accommodation, assimilation, and continuing bonds.
AB  - Reactions to death have been studied extensively from psychological, behavioral,
      and physiological perspectives. Occupational adaptation to loss has received
      scant attention. Qualitative research was undertaken to identify and describe
      occupational responses in bereavement. The constant comparative approach was used
      to analyze and interpret the occupational responses. Adaptive strategies of
      occupational accommodation and assimilation were used after the death of a family
      member. Desire to sustain bonds with the deceased motivated specific occupational
      engagements. These occupational responses served to reconstruct meaning after the
      death of a family member. These findings contribute to understanding adaptation
      after death by adding an occupational perspective to previous theories.
      Occupational therapists' abilities to support clients after loss can be enhanced
      through appreciation of occupational accommodation and assimilation and the role
      of continuing occupational bonds after the death of a loved one.

PMID- 20131574
TI  - Doing, being, and becoming: a family's journey through perinatal loss.
AB  - Occupational therapists are encouraged to reflect on doing, being, and becoming
      not only as it relates to the development of their profession but also in their
      own lives (Wilcock 1999). This article is a description of that process for me
      and my family in our journey through perinatal loss. This autoethnography uses a
      personally situated account of perinatal death. This article is a form of self
      narrative that places me and my family in social context through the lens of an
      occupational therapist. This article aims to convey the meanings attached to the
      experience of grief and loss in the context of participation in everyday
      occupations. By sharing a perspective on the lived experience and connecting it
      to the literature on grief and occupation, readers will be able to decide if the
      connection holds as valid from a theoretical and clinical perspective.

PMID- 20131575
TI  - Beyond flow: temporality and participation in everyday activities.
AB  - Experience sampling examined how temporality, the lived experience of time,
      varied related to specific activity qualities and experiences in everyday life.
      Thirty-five students completed electronic surveys regarding their current
      activity and feelings and rated the activity's novelty and complexity, their
      depth of emotional and intellectual engagement, the direction and depth of
      attention, and the demands of the activity on their skills. Using configural
      frequency analysis and an analysis of narrative responses, configurations of
      factors (types) associated with variations in perceived temporalities were
      described. Four composite types identified occurred with any temporality. In most
      habitual activities, time was perceived as passing the same as clock time. Most
      faster or timeless temporalities occurred in complex, novel, and skill-requiring
      activities that engaged participants. Unexpected activity configurations were
      also associated with accelerated perceptions of time. Occupational therapists may
      use this knowledge to assist clients to redesign activities that promote positive
      experiences without high activity demands.

PMID- 20131576
TI  - Facilitating evidence-based practice: process, strategies, and resources.
AB  - Occupational therapy practitioners may encounter challenges when they try to
      incorporate evidence into practice. To embrace evidence-based practice (EBP),
      clinicians must have readily available, relevant, and concisely summarized
      evidence. Although researchers have described the importance and process of EBP,
      less has been written about how to efficiently integrate evidence into practice.
      Clinicians may benefit from examples of reasoning, strategies, and resources to
      successfully integrate evidence. This article reviews the steps of EBP and offers
      recommendations to overcome common barriers. For EBP to become integrated into
      practice, greater communication and collaboration among all stakeholders must
      occur. EBP and knowledge translation require multiple processes and coordinated
      efforts. Therefore, everyone from practitioners to employers has a role in
      increasing EBP and transferring knowledge for practice. To encourage discussion
      and actions, the article provides implications and recommendations for
      practitioners, researchers, educators, organizations, and policymakers.

PMID- 20131577
TI  - Geriatric research.
AB  - The American Occupational Therapy Association's Centennial Vision articulates the
      need for occupational therapy to be science driven and evidence based in major
      practice areas. This article provides a review on the state of the occupational
      therapy research published in the American Journal of Occupational Therapy (AJOT)
      in the area of productive aging in the past 2 years (2008-2009). The article
      identifies the types of research published, assesses how well the journal is
      meeting the Centennial Vision in productive aging research, and discusses
      implications for utilization of the evidence by occupational therapy
      practitioners. Although many basic research articles provide a foundation for
      future intervention development and further define practice roles, the AJOT
      articles addressing productive aging represent diverse research questions and
      have produced a body of knowledge that is not easily translated to practice. More
      effectiveness studies are needed to provide adequate evidence for occupational
      therapy intervention with older adults.

PMID- 20131578
TI  - Cognitive versus functional approaches to rehabilitation after traumatic brain
      injury: commentary on a randomized controlled trial.
AB  - I describe the findings of one of the largest randomized controlled trials (RCTs)
      of rehabilitation after traumatic brain injury (TBI) ever conducted, examine the
      theoretical relationship between cognitive and functional rehabilitation after
      TBI, and describe the historical preference for cognitive (top-down) rather than
      functional (bottom-up) interventions. I also contrast the goals and principles of
      cognitive rehabilitation and of the neurofunctional approach of Giles and Clark
      Wilson (1993; Giles, 2005)--a bottom-up approach. Findings of the RCT provide
      empirical support for both functional and cognitive interventions following acute
      TBI. In addition, they provide evidence that each type of intervention offers
      significant advantages for a specific subpopulation. The clinical implications of
      these findings for occupational therapy practitioners are discussed.

PMID- 20131579
TI  - Blueprint for entry-level education.

PMID- 20131580
TI  - Ambiguity in palliative care?

PMID- 20131581
TI  - Satisfaction with end-of-life care: a longitudinal study of patients and their
      family caregivers in the last months of life.
AB  - To determine whether and how ratings of satisfaction with end-of-life (EOL) care
      change over time and across settings, we administered a satisfaction
      questionnaire to patients 55 years and older with advanced medical disease and
      their family caregivers (FCGs). We re-interviewed approximately every two months
      for a maximum of four visits. Overall, 97 patients and 68 FCGs completed a
      baseline interview; 57 and 40 completed two interviews, 35 and 22 completed
      three, and 15 and 10 completed four. Patient satisfaction increased over time and
      in three of the six questionnaire domains, but this was largely confounded with
      the location of interview. Satisfaction scores were greater among patients whose
      baseline interviews occurred at home. FCGs reported increased satisfaction over
      time; members of the subgroup that cared for patients who died during the study
      were less satisfied in the spirituality domain during bereavement than prior to
      their relative's death. Satisfaction with care tends to vary based on location of
      interview and may vary across time with respect to certain aspects of EOL care.

PMID- 20131582
TI  - Chronic palliative care: specific practices for Alzheimer's disease sufferers.
AB  - INTRODUCTION: In France, the government's plan to combat Alzheimer's disease
      takes into consideration mostly the beginnings of the disease; it does not deal
      with the sufferers' end of life. For this pathology, the very idea of a
      palliative care phase and its definition are not straightforward. METHOD: The
      object of this qualitative study was to clarify this idea through a series of
      interviews with 44 professionals. RESULTS: The study describes three successive
      phases in the disease trajectory, revealed by changes in the logic of care: the
      stimulation phase, the chronic palliative care phase, and the terminal palliative
      phase. CONCLUSION: Alzheimer's disease has a specific phase of chronic palliative
      care. It presents, for professionals, several types of problems related to
      communication, pain, and feeding.

PMID- 20131583
TI  - Involvement of nurses in the euthanasia care process in Flanders (Belgium): an
      exploration of two perspectives.
AB  - This study explored nurses' involvement in the care process for mentally
      competent, terminally ill patients requesting euthanasia in general hospitals in
      Flanders, Belgium. In-depth interviews with 18 nurses who had experience in
      caring for patients requesting euthanasia since May 2002 were analyzed using
      grounded theory qualitative methods. We found that the involvement of nurses in
      the care process is influenced by their predominant perspective on it: the
      procedural, action-focused perspective, from which good practical organization of
      the care process is essential; or the existential-interpretative perspective,
      from which it is important to understand the patient's request within a dialogue
      focused and communicational atmosphere. Findings show that the two perspectives
      are not mutually exclusive, but rather complementary dimensions of the euthanasia
      care process. Hence, sufficient support for nurses to reach a well-balanced
      integration of both perspectives is essential.

PMID- 20131584
TI  - Understanding the provision of palliative care in the context of primary health
      care: qualitative research findings from a pilot study in a community setting in
      Chile.
AB  - This pilot study looked at the provision of palliative care in the context of
      primary health care in a developing setting in Chile. RESEARCH OBJECTIVES: The
      study aimed to delineate the experience of palliative care from the perspective
      of patients and health care professionals; to examine primary health care as a
      propitious milieu for palliative care in developing countries; and to generate
      opportunities for international collaboration between Chile and Canada.
      METHODOLOGY: The study followed tenets of hermeneutic phenomenology and
      participatory research. Research activities included audio-taped, in-depth
      individual interviews and participant observation in the home. RESULTS: Patients
      expressed contentment with the services provided by the program. The support of
      family members, friends, neighbours, and the palliative team was critical to
      their home care. Health care professionals showed great enthusiasm for keeping
      the palliative care program going in the primary health care setting despite
      limited resources. They followed WHO and national guidelines for symptom relief
      and involved families in the care of the sick person. CONCLUSION: The provision
      of palliative care through primary health care increases access in developing
      countries.

PMID- 20131585
TI  - The Israeli terminally ill patient law of 2005.
AB  - Israel, like many other countries, is struggling with numerous bioethical
      dilemmas due to its cultural and religious diversity. Until recently there was no
      legal guidance for how to deal with end-of-life issues. However, in 2005 a law
      was passed regulating the treatment of dying patients. Its most controversial
      aspect is the distinction it makes between withholding therapy (which is allowed)
      and withdrawing continuous therapy (which is not allowed). In this formulation,
      the law attempted to strike a balance between respecting the autonomy of the
      patient and respecting the sanctity of life. The law respects autonomy by
      establishing the right of the patient to refuse treatment; it respects the
      sanctity of life by prohibiting active euthanasia and physician-assisted suicide.
      However, this compromise was not acceptable to all members of the public advisory
      body that framed the law. Some argued that there was no moral basis for the
      distinction between withholding and withdrawing treatment.

PMID- 20131586
TI  - Home hospice care for the lung cancer patient living alone: a case report from
      Japan.

PMID- 20131587
TI  - Cradled between heaven and earth. A reply to my patient's family: why I couldn't
      offer active euthanasia when you asked for it.

PMID- 20131588
TI  - The fire hall.

PMID- 20131589
TI  - Transdermal fentanyl: not ready for front line.

PMID- 20131590
TI  - Distribution of polycyclic aromatic hydrocarbons in sediments from Yellow River
      Estuary and Yangtze River Estuary, China.
AB  - Surface sediment samples collected from twenty-one sites of Yellow River Estuary
      and Yangtze River Estuary were determined for sixteen priority polycyclic
      aromatic hydrocarbons (PAHs) by isotope dilution GC-MS method. The total PAH
      contents varied from 10.8 to 252 ng/g in Yellow River Estuary sediment, and from
      84.6 to 620 ng/g in Yangtze River Estuary sediment. The mean total PAH content of
      Yangtze River Estuary was approximately twofold higher than that of Yellow River
      Estuary. The main reasons for the difference may be the rapid industrial
      development and high population along Yangtze River and high silt content of
      Yellow River Estuary. The evaluation of PAH sources suggested that PAHs in two
      estuaries sediments estuaries were derived primarily from combustion sources, but
      minor amounts of PAHs were derived from petroleum source in Yellow River Estuary.
      PAHs may be primary introduced to Yellow River Estuary via dry/wet deposition,
      wastewater effluents, and accidental oil spills, and Yangtze River Estuary is
      more prone to be affected by wastewater discharge.

PMID- 20131591
TI  - Variation of phytoplankton community before an induced cyanobacterial
      (Arthrospira platensis) bloom.
AB  - A cyanobacterial (Arthrospira platensis) bloom was induced in situ by nutrient
      manipulation in an enclosure. The succession of the phytoplankton community and
      the water chemistry variations before the appearance of bloom, as well as their
      relationship, were investigated. The cell pigment variations were studied
      simultaneously. The Pearson's correlation analysis showed that there was no
      significant correlation between water chemistry and green algal or cyanobacterial
      composition, indicating that water chemistry variations were not suitable to be
      used as indicators for cyanobacterial-bloom early-warning. However, the diversity
      index of the phytoplankton community decreased sharply before the bloom appeared.
      Therefore, the dynamics of phytoplankton community was put forward to be an
      indicator for cyanobacterial-bloom early-warning. In addition, the cell pigment
      variations represented the changes of community structure, which should be useful
      for studying the dynamics of phytoplankton community.

PMID- 20131592
TI  - Simulation and assessment of sludge concentration and rheology in the process of
      waste activated sludge treatment.
AB  - The process of using flat-sheet membrane for simultaneous sludge thickening and
      digestion (MSTD) was employed. The variations of sludge concentration and
      rheology were characterized and simulated. Based on mass balance analysis,
      mathematical models were developed and successfully used to predict and evaluate
      the variations of sludge concentration and the digestion efficiency in the MSTD
      process. The apparent viscosity of sludge could be modeled as functions of mixed
      liquor suspended solids and shear rates. The sludge in the MSTD process showed
      both shear-thinning and viscoplastic behaviour, and under various shear rates
      different rheological models could be chosen to predict their flow behaviour. It
      was also found that sludge concentration and viscosity had significant
      correlations with membrane fouling in the MSTD process.

PMID- 20131593
TI  - Design of reaction conditions for the enhancement of microbial degradation of
      dyes in sequential cycles.
AB  - The present study evaluated the potential of white-rot fungal strain Coriolus
      versicolor to decolorize five structurally different dyes in sequential batch
      reactors under optimized conditions. The experiments were run continuously for
      seven cycles of 8 d each. High decolorizing activity was observed even during the
      repeated reuse of the fungus, especially when the old medium was replaced with
      fresh medium after every cycle. Biodegradation was the dominating factor as the
      fungus was able to produce the enzyme laccase mainly, to mineralize synthetic
      dyes. The nutrients and composition of the medium played important roles in
      sustaining the decolorisation potential of the fungus. Corncob was found be an
      easy and cheap substitute for carbon source for the fungus. Glucose consumption
      by the fungus was in accordance to its decolorisation activity and chemical
      oxygen demand (COD) reduction.

PMID- 20131594
TI  - Oxidation of gaseous elemental mercury in a high voltage discharge reactor.
AB  - Effects of the voltage waveform, discharge tooth wheel number and CO2/NO/SO2
      concentration in the simulated flue gas on Hgo oxidation were investigated using
      a link tooth wheel-cylinder reactor energized by different high voltage power
      supplies. Negative DC discharge induced more ozone production and a higher Hg0
      oxidation efficiency than positive DC discharge and 12 kHz AC discharge. The
      discharge tooth wheel number had almost no effect on the maximum Hg0 oxidation
      efficiency. The allowable supplied voltage decreased with the increase of
      discharge tooth wheel number. CO2 could stabilize the discharge process and
      increase the maximum voltage for a stable discharge. It has also been found that
      NO consumed O3 induced by high voltage discharge, thereby decreased Hg0 oxidation
      efficiency; while SO2 had a slight promoting effect on Hg0 oxidation.

PMID- 20131595
TI  - Characterization of organic matter in total suspended particles by
      thermodesorption and pyrolysis-gas chromatography-mass spectrometry.
AB  - The organic matter in tropospheric aerosol plays an important role in atmospheric
      physical and chemical processes. The bulk of organic matter, representing a
      significant proportion of the total suspended particulate (TSP) mass, is bound to
      polymeric material whose structure and properties are largely unknown. Here we
      used thermodesorption gas chromatography/mass spectrometry (Td-GC/MS) to study
      organic compounds of low molecular mass and pyrolysis gas chromatography/mass
      spectrometry (Py-GC/MS) to characterize the chemical structure of macromolecules
      in TSP samples collected in different seasons from different sites in Guangzhou.
      n-Alkanes, fatty acids and nitriles were the predominant compounds in the
      thermodesorption products, whereas aromatics, fatty acids, nitriles and n
      alkanes/alkenes were the major compounds in the pyrolysates. The results
      indicated that aromatics were main units in macromolecules. The fatty acids and
      nitriles formed from carboxylic ammonium salts were detected in both
      thermodesorption products and pyrolysates at a certain concentration, indicating
      the importance of these compounds in TSP formation. The TSP source mainly
      determined the occurrence of compounds in samples from urban, suburban and forest
      sites, whereas the TSP source and formation process maybe controlled the seasonal
      variation in compounds detected. High levels of nitriles in summer samples from
      suburban and forest sites coincide with the release of ammonium from the land and
      of fatty acids from vegetation at these sites.

PMID- 20131596
TI  - Soluble protein and acid phosphatase exuded by ectomycorrhizal fungi and
      seedlings in response to excessive Cu and Cd.
AB  - Fungi and their symbionts can alleviate heavy metal stress by exuding soluble
      proteins and enzymes. This study examined the role of soluble protein and acid
      phosphatase (APase) exuded by Xerocomus chrysenteron, an ectomycorrhizal fungus,
      and the seedlings of its symbiont, Chinese pine (Pinus tabulaeformis), under
      conditions of excessive Cu and Cd. The growth type showed that this poorly
      studied ectomycorrhizal fungus was capable of tolerating high concentrations of
      Cu, and may be useful in phytoremediation. X. chrysenteron grew well at 80 mg/L
      Cu, and the EC50 for Cd was 17.82 mg/L. X. chrysenteron also showed enhanced
      exudation of soluble protein in both isolated and inoculated cultivations under
      the influence of Cu and Cd. Soluble protein exudation, however, differed under Cu
      and Cd stress in isolates. In mediums containing Cu, soluble protein exudation
      increased with concentration, but in mediums containing Cd the content of soluble
      protein increased to a comparable level at all concentrations. This study
      demonstrated that soluble protein was related to heavy metal tolerance, although
      the different ions played different roles. While APase activity in exudates of
      fungi and seedlings decreased under Cu and Cd stress in comparison to the
      control, the APase activity in seedlings was maintained by inoculation. Thus, X.
      chrysenteron facilitated the ability of plant to maintain a normal nutrient
      uptake, and therefore to protect it from heavy metal toxicity.

PMID- 20131597
TI  - Identification and characterization of the chromium (VI) responding protein from
      a newly isolated Ochrobactrum anthropi CTS-325.
AB  - A Gram-negative, chromium(VI) tolerant and reductive strain CTS-325, isolated
      from a Chinese chromate plant, was identified as Ochrobactrum anthropi based on
      its biochemical properties and 16S rDNA sequence analysis. It was able to
      tolerate up to 10 mmol/L Cr(VI) and completely reduce 1 mmol/L Cr(VI) to Cr(III)
      within 48 h. When the strain CTS-325 was induced with Cr(VI), a protein increased
      significantly in the whole cell proteins. Liquid chromatography tandem mass
      spectrometry (LC-MS/MS) analysis revealed that this protein was a superoxide
      dismutase (SOD) homology. The measured superoxide dismutase activity was 2694
      U/mg after three steps of purification. The SOD catalyzes the dismutation of the
      superoxide anion (O2*-) into hydrogen peroxide and molecular oxygen. This protein
      is considered to be one of the most important anti-oxidative enzymes for O.
      anthropi as it allows the bacterium to survive high oxygen stress environments,
      such as the environment produced during the reduction process of Cr(VI).

PMID- 20131598
TI  - Carbendazim induces a temporary change in soil bacterial community structure.
AB  - The effect of carbendazim applications on the diversity and structure of a soil
      bacterial community was studied under field conditions using temperature gradient
      gel electrophoresis (TGGE) and partial sequence analysis of PCR-amplified 16S
      rRNA gene. After four successive introductions of carbendazim at a level of 0.94
      kg active ingredient (a.i.)/ha, the genetic diversity (expressed as Shannon
      index, H') decreased from 1.43 in the control to 1.29 in treated soil. This
      harmful effect seems to increase with the concentration of carbendazim. The value
      of H' in the soil treated with carbendazim at 4.70 kg a.i./ha was reduced to 1.05
      (P < or = 0.05). The structure of soil bacterial community was also affected
      after four repeated applications of carbendazim at levels of 0.94, 1.88 and 4.70
      kg a.i./ha, as seen in the relative intensities of the individual band. However,
      the bacterial community in carbendazim-treated soil recovered to that in the
      control 360 d after the first treatment. The results indicated that repeated
      applications of carbendazim could reduce soil microbial diversity and alter the
      bacterial community structure temporarily.

PMID- 20131599
TI  - Adverse effects of metal exposure on chemotaxis towards water-soluble attractants
      regulated mainly by ASE sensory neuron in nematode Caenorhabditis elegans.
AB  - Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory
      neuron whose specification is regulated by che-1 in Caenorhabditis elegans. Our
      data suggested that exposure to high concentrations of metals, such as Pb, Cu,
      Ag, and Cr, would result in severe defects of chemotaxis to water-soluble
      attractants of NaCl, cAMP, and biotin. Moreover, the morphology of ASE neuron
      structures as observed by relative fluorescent intensities and relative size of
      fluorescent puncta of cell bodies, relative lengths of sensory endings in ASE
      neurons, and the expression patterns of che-1 were obviously altered in metal
      exposed animals when they meanwhile exhibited obvious chemotaxis defects to water
      soluble attractants. In addition, the dendrite morphology could be noticeably
      changed in animals exposed to 150 micromol/L of Pb, Cu, and Ag. Furthermore, we
      observed significant decreases of chemotaxis to water-soluble attractants in Pb
      exposed che-1 mutant at concentrations more than 2.5 micromol/L, and in Cu, Ag,
      and Cr exposed che-1 mutant at concentrations more than 50 micromol/L. Therefore,
      impairment of the ASE neuron structures and functions may largely contribute to
      the appearance of chemotaxis defects to water-soluble attractants in metal
      exposed nematodes.

PMID- 20131600
TI  - Ecotoxicological effects of mixed pollutants resulted from e-wastes recycling and
      bioaccumulation of polybrominated diphenyl ethers in Chinese loach (Misgurnus
      anguillicaudatus).
AB  - To understand potential ecotoxicological effects of electrical and electronic
      equipment waste (e-waste) recycling and polybrominated diphenyl ethers (PBDEs)
      bioaccumulation in loaches, a semi-field experiment using Chinese loach
      (Misgurnus anguillicaudatus) as experimental fish was performed. Larval loaches
      were kept in net-cage for three months in an e-wastes recycling site and a
      reference site in Southeastern China. There was significant difference of the
      survival rate between the loaches from the e-wastes recycling site (27%, 19/70)
      and from reference site (70%, 49/70). Histopathological responses were also found
      in all the livers examined in loaches from the e-wastes recycling site. These
      results showed that mixed pollutants resulted from e-wastes recycling led to
      ecotoxicological effects on loaches. The bioaccumulation of polybrominated
      diphenyl ethers (PBDEs), the main pollutants in e-waste, in loaches was also
      studied, the mean concentration of total PBDEs in sediment was 6726.17 ng/g wet
      weight and in water samples was 4.08 ng/L (dissolved phase). BDE 209 was the
      dominant congener in sediment and with relatively high concentration in water.
      Relatively low concentration of BDE 209 (less than 0.01% of total PBDEs) and high
      concentration of BDE47 (up to 39.34% of total PBDEs) were detected in loaches.

PMID- 20131601
TI  - Assessing the health risk of heavy metals in vegetables to the general population
      in Beijing, China.
AB  - A systematic survey of As, Cd, Cr, Cu, Ni, Pb and Zn concentrations in vegetables
      from 416 samples (involving 100 varieties) in Beijing was carried out for
      assessing the potential health risk to local inhabitants. The results indicated
      that the metal concentrations in vegetables ranged from < 0.001 to 0.479 microg/g
      fresh weight (fw) (As), < 0.001 to 0.101 microg/g fw (Cd), < 0.001 to 1.04
      microg/g fw (Cr), 0.024 to 8.25 microg/g fw (Cu), 0.001 to 1.689 microg/g fw
      (Ni), < 0.001 to 0.655 microg/g fw (Pb) and 0.01 to 25.6 microg/g fw (Zn), with
      average concentrations of 0.013, 0.010, 0.023, 0.51, 0.053, 0.046 and 2.55
      microg/g fw, respectively. The results showed that the concentrations of As, Cr,
      Cu, Cd, Pb and Ni in vegetables from open-fields were all significantly higher
      than those grown in greenhouses. In addition, in local-produced vegetables, all
      HMs except Zn were significantly higher than those in provincial vegetables. The
      estimated daily intake (EDI) of As, Cd, Cr, Cu, Ni, Pb and Zn from vegetables was
      0.080, 0.062, 0.142, 3.14, 0.327, 0.283 and 15.7 microg/(kg body weight (bw) x d)
      for adults, respectively. Arsenic was the major risk contributor for inhabitants
      since the target hazard quotient based on the weighted average concentration
      (THQw) of arsenic amounted to 44.3% of the total THQ (TTHQ) value according to
      average vegetable consumption. The TTHQ was lower than 1 for all age groups,
      indicating that it was still safe for the general population of Beijing to
      consume vegetables.

PMID- 20131602
TI  - Chronic toxicity and cytotoxicity of synthetic pyrethroid insecticide cis
      bifenthrin.
AB  - With the increasing use of synthetic pyrethroids (SPs), the significance of
      ecological safety and health risk is an emerging concern. In this study, we
      evaluated the chronic aquatic toxicity of cis-bifenthrin (cis-BF) in Daphnia
      magna and its cytotoxicity in Chinese hamster ovary (CHO) cells as well as human
      cervical carcinoma (Hela) cells. Chronic aquatic toxicity tests showed that cis
      BF could significantly affect the reproduction of D. magna. The lowest observed
      effective concentration and the non-observed effective concentration of cis-BF to
      D. magna were 0.02 and 0.01 microg/L, respectively, and the chronic value was
      0.014 microg/L. The intrinsic rate of natural increase was significantly
      decreased (p < 0.05) to 0.02 microg/L. The cytotoxicity assay demonstrated that
      cis-BF decreased cell viability in CHO and Hela cells in a concentration- and
      time-dependent manner. The IC50 values for Hela and CHO cells were 4.0 x 10(-5)
      and 3.2 x 10(-5) mol/L, respectively. Together, these results indicated that cis
      BF induced chronic toxicity in both aquatic invertebrate animals and mammalian
      cells. These findings assist in understanding the impact of SPs on health and
      environmental safety. Considering the wide spectrum of SPs, a more comprehensive
      understanding of the negative effects is indispensible for planning future
      application and regulation of these pesticides.

PMID- 20131603
TI  - Effects of methyl-, phenyl-, ethylmercury and mercurychlorid on immune cells of
      harbor seals (Phoca vitulina).
AB  - Mercury (Hg) is present in the marine environment as a natural metal often
      enhanced through human activities. Depending on its chemical form, Hg can cause a
      wide range of immunotoxic effects. In this study, the influence of methyl-, ethyl
      and phenylmercury as well as mercurychloride on immune functions was evaluated.
      Two parameters of cellular immunity, proliferation and mRNA cytokine expression
      of interleukin-2, -4, and transforming growth factor beta, were investigated in
      harbor seal lymphocytes after in vitro exposure to Hg compounds. While all Hg
      compounds had a suppressive effect on proliferation, differences between juvenile
      and adult seals were found. Lymphocytes from juveniles showed a higher
      susceptibility to the toxic effect compared to lymphocytes from adults.
      Furthermore, the degree of inhibition of proliferation varied among the four Hg
      compounds. The organic compounds seem to be more immunotoxic than the inorganic
      compound. Finally, for the cytokine expression of methylmercury-incubated
      lymphocytes, time-dependent changes were observed, but no dose-dependency was
      found. Marine mammals of the North Sea are burdened with Hg, and lymphocytes of
      harbor seals may be functionally impaired by this metal. The present in vitro
      study provides baseline information for future studies on the immunotoxic effects
      of Hg on cellular immunity of harbor seals.

PMID- 20131604
TI  - Synthesis, characterization, and adsorption performance of Pb(II)-imprinted
      polymer in nano-TiO2 matrix.
AB  - Surface ion-imprinted in combination with sol-gel process was applied to
      synthesis a new Pb(II)-imprinted polymer for selective separation and enrichment
      of trace PbO(II) from aqueous solution. The prepared material was characterized
      by using the infrared spectra, X-ray diffractometer, and scanning electron
      microscopy. The batch experiments were conducted to study the optimal adsorption
      condition of adsorption trace Pb(II) from aqueous solutions on Pb(II)-imprinted
      polymer. The equilibrium was achieved in approximately 4.0 h, and the
      experimental kinetic data were fitted the pseudo second-order model better. The
      maximum adsorption capacity was 22.7 mg/g, and the Langmuir equation fitted the
      adsorption isotherm data. The results of selectivity experiment showed that
      selectively adsorbed rate of Pb(II) on Pb(II)-imprinted polymer was higher than
      all other studied ions. Desorption conditions of the adsorbed Pb(II) from the
      Pb(II)-imprinted polymer were also studied in batch experiments. The prepared
      Pb(II)-imprinted polymer was shown to be promising for the separation and
      enrichment of trace Pb(II) from water samples. The adsorption and desorption
      mechanisms were proposed.

PMID- 20131605
TI  - Heavy metal removal from aqueous solution using carbonaceous K2S-impregnated
      adsorbent.
AB  - A novel carbonaceous adsorbent for heavy metal removal was prepared from raw coal
      by one-step simple sulfur impregnation using K2S. Raw coal was mixed with K2S
      powder and then heated at 800 degrees C for 30 min in nitrogen to produce K2S
      char. The sulfur content and form in K2S char were determined, and the ability of
      K2S char to adsorb Zn2+, Cd2+ and Pb2+ was examined. The K2S impregnation was
      effective at impregnating sulfur into coal, especially in the form of elemental,
      thiophenic and sulfatic sulfur. The sulfur content of K2S char was higher than
      those of raw coal and pyrolysis char. The Zn2+ removal in 2.4 mmol/L of Zn2+
      solution by K2S char was higher than raw coal with the removal rate of 100%. K2S
      char adsorbed Pb2+ and Cd2+ in 24 mmol/L of Pb2+ and Cd2+ solution with the
      removal rate of 97% and 35%, respectively. The elution extents of adsorbed Pb2+
      and Cd2+ were zero in distilled water and 27% in 0.1 mol/L HCl solution. These
      results indicated that an effective adsorbent for heavy metal ions was prepared
      from coal using K2S sulfur impregnation, and that the adsorbed metals were
      strongly retained in K2S char.

PMID- 20131606
TI  - Remediation of sulfidic wastewater by catalytic oxidation with hydrogen peroxide.
AB  - Oxidation of sulfide in aqueous solution by hydrogen peroxide was investigated in
      the presence of hydrated ferric oxide catalyst. The ferric oxide catalyst was
      synthesized by sol gel technique from ferric chloride and ammonia. The
      synthesized catalyst was characterized by Fourier transform infrared
      spectroscopy, X-Ray diffraction analysis, scanning electrom microscope and energy
      dispersive X-ray analysis. The catalyst was quite effective in oxidizing the
      sulfide by hydrogen peroxide. The effects of sulfide concentration, catalyst
      loading, H2O2 dosing and temperature on the kinetics of sulfide oxidation were
      investigated. Kinetic equations and activation energies for the catalytic
      oxidation reaction were calculated based on the experimental results.

PMID- 20131607
TI  - Enhancement of formaldehyde degradation by amine functionalized silica/titania
      films.
AB  - Doping amine functional groups into SiO2/TiO2 films for enhancing the
      decomposition of formaldehyde has been investigated using the modified sol-gel
      method to prepare organic-inorganic hybrid photocatalysts via the co-condensation
      reaction of methyltrimethoxysilane (MTMOS) and amine functional groups. n-(2
      Aminoethyl)-3-aminopropyl-trimethoxysilane (AEAPTMS) and 3-aminopropyl
      trimethoxysilane (APTMS) were selected to study the effect of amine functional
      groups on the enhancement of formaldehyde adsorption and degradation under a UV
      irradiation process. Physicochemical properties of prepared photocatalysts were
      characterized with nitrogen adsorption-desorption isotherms measurement, X-ray
      diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy. The
      results indicated that the APTMS/SiO2/TiO2 film demonstrated a degradation
      efficiency of 79% superior to those of SiO2/TiO2 and AEAPTMS/SiO2/TiO2 films due
      to the synergetic effect of adsorption and photocatalytic properties. The
      APTMS/SiO2/TiO2 film can be recycled with about 7% decreasing of degradation
      efficiency after seven cycles.

PMID- 20131608
TI  - Emission characteristics of dioxins, furans and polycyclic aromatic hydrocarbons
      during fluidized-bed combustion of sewage sludge.
AB  - Pre-dried sewage sludge with high sulfur content was combusted in an electrically
      heated lab-scale fluidized-bed incinerator. The emission characteristics of
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs)
      and polycyclic aromatic hydrocarbons (PAHs) were studied. Coal and calcium oxide
      (CaO) were added during the sewage sludge combustion tests to optimize combustion
      conditions and control SO2 emission. The results indicated that the flue gases
      emitted during mono-combustion of sewage sludge were characterized by relatively
      high concentrations of SO2, NOx and organic pollutants, due to the high sulfur,
      nitrogen, and volatile matter content of sewage sludge. The total 16 USEPA
      priority PAHs and 2,3,7,8-substituted PCDD/Fs produced from sewage sludge
      combustion were found to be 106.14 microg/m3 and 8955.93 pg/m3 in the flue gas,
      respectively. In the case of co-combustion with coal (m(sludge)/m(coal) = 1:1),
      the 16 PAHs and 2,3,7,8-substituted PCDD/Fs concentrations were markedly lower
      than those found during mono-combustion of sewage sludge. During co-combustion, a
      suppressant effect of CaO on PCDD/Fs formation was observed.

PMID- 20131609
TI  - Leaching of phosphorus from incinerated sewage sludge ash by means of acid
      extraction followed by adsorption on orange waste gel.
AB  - Ashes from sewage sludge incineration have a high phosphorus content,
      approximately 8% (W/W), which indicates a potential resource of the limiting
      nutrient. Incineration of sewage sludge with subsequent recovery of phosphorus is
      a relatively new sludge treatment technique. In this article, the leaching of
      phosphorus by using sulfuric acid as well as hydrochloric acid by means of
      several batch experiments was presented. At the same time a selective recovery of
      phosphorus by adsorption was also discussed. The effects of acid concentration,
      temperature and time on extraction were studied. The phosphorus leaching
      increased with the increase in acid concentration and temperature. Kinetic
      studies showed that the complete leaching of phosphorus took place in less than 4
      h. Selective adsorption of phosphorus by using orange waste gel provided a hint
      for recovery of this natural resource, which eventually could meet the ever
      increasing requirement for phosphorus. The overall results indicated that the
      incinerated sewage sludge ash can be treated with acid to efficiently recover
      phosphorus and thus can be considered a potentially renewable source of
      phosphorus.

PMID- 20131610
TI  - Mechanochemical decomposition of pentachlorophenol by ball milling.
AB  - The mechanochemical dechlorination of pentachlorophenol (PCP) was studied using
      CaO and SiO2 powder as additives. The effects of the milling time and additives
      on the dechlorination rate were investigated. The resulting product was
      characterized by X-ray diffraction (XRD), Fourier transform infrared spectra (FT
      IR), thermogravimetric analysis (TG) and ion chromatography (IC). It is found
      that grinding operation could dechlorinate PCP, with the formation of inorganic
      chloride and amorphous carbon. The addition of quartz to the grinding mixture
      facilitated dechlorination. On the basis of the experimental results, the
      decomposition mechanism was proposed. Decomposition predominantly proceeds
      through rupture of C-Cl bond in PCP molecule, followed by the formation of
      inorganic chlorides.

PMID- 20131611
TI  - Improved preparation and identification of aristolochic acid-DNA adducts by solid
      phase extraction with liquid chromatography-tandem mass spectrometry.
AB  - Aristolochic acid (AA) is a known nephrotoxin and potential carcinogen, which can
      form covalent DNA adducts after metabolic activation in vivo and in vitro. A
      simple method for preparation and characterization of aristolochic acid-DNA
      adducts was developed. Four AA-adducts were synthesized by a direct reaction of
      AAI/AAII with 2'-deoxynucleosides. The reaction mixture was first cleaned-up and
      pre-concentrated using solid phase extraction (SPE), and further purified by a
      reversed-phase high performance liquid chromatography (HPLC). By the application
      of developed SPE procedure, matrices and byproducts in reaction mixture could be
      greatly reduced and adducts of high purity (more than 94% as indicated by HPLC)
      were obtained. The purified AA-DNA adducts were identified and characterized with
      liquid-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC
      ESI-Q-TOF-MS/MS) and LC-Diode array detector-fluorescence (LC-DAD-FL) analysis.
      This work provides a robust tool for possible large-scale preparation of AA-DNA
      adduct standards, which can promote the further studies on carcinogenic and
      mutagenic mechanism of aristolochic acids.

PMID- 20131612
TI  - Mouthguards in Texas: let's have a conversation.

PMID- 20131613
TI  - Antimicrobial efficacy of soap and water hand washing versus an alcohol-based
      hand cleanser.
AB  - The emergence of alcohol-based hand cleansers may represent an alternative to
      soap and water in the clinical dental setting. In this study, the antimicrobial
      efficacy of traditional hand washing vs. a unique alcohol-based hand cleanser
      with persistence was evaluated. Two experienced dentists participated over a 10
      day period. On days 1-5, each clinician used an antibacterial liquid soap (Dial,
      Dial Corporation, Scottsdale, AZ). Days 6-10, an alcohol-based hand cleanser
      (Triseptin Water Optional, Healthpoint Surgical, Fort Worth, TX) was used.
      Sampling was by modified glove juice technique. The results indicate that the
      alcohol-based hand cleanser dramatically outperforms the traditional hand washing
      agent in the general dental setting.

PMID- 20131614
TI  - Dental surgery for patients on anticoagulant therapy with warfarin: a systematic
      review and meta-analysis.
AB  - PURPOSE: To evaluate the effect of continuing warfarin therapy on the bleeding
      risk of patients undergoing elective dental surgical procedures. METHODS: Data
      sources were the MEDLINE and EMBASE databases, the Cochrane Central Register of
      Controlled Trials, a manual citation review of the relevant literature, content
      experts and relevant abstracts from the proceedings of the International
      Association for Dental Research. Study selection was carried out independently by
      two reviewers, as was quality assessment. Data extraction was done by three
      reviewers. Differences were resolved by consensus. Eligible studies were
      randomized controlled trials that compared the effects of continuing the regular
      dose of warfarin therapy with the effects of discontinuing or modifying the dose
      on the incidence of bleeding in patients undergoing dental procedures. RESULTS:
      Five trials (a total of 553 patients) met the inclusion criteria. Compared with
      interrupting warfarin therapy (either partial or complete), perioperative
      continuation of warfarin with patients' usual dose was not associated with an
      increased risk for clinically significant nonmajor bleeding (relative risk [RR],
      0.71; 95 percent confidence interval [CI]: 0.39-1.28; p = 0.65; 12 = 0%) or an
      increased risk for minor bleeding (RR, 1.19; 95% CI: 0.90-1.58; p = 0.22; 12 =
      0%). CONCLUSIONS: Continuing the regular dose of warfarin therapy does not seem
      to confer an increased risk of bleeding compared with discontinuing or modifying
      the warfarin dose for patients undergoing minor dental procedures.

PMID- 20131615
TI  - Understanding the envelope of parafuntion.

PMID- 20131616
TI  - Oral and maxillofacial pathology case of the month. Tonsillolith.

PMID- 20131617
TI  - Wilensky joins BrainScope's board. A veteran of numerous boards, former Bush
      adviser says no conflicts present.

PMID- 20131618
TI  - A strong pulse in doc recruiting. Competition for physicians remains intense as
      the younger generation, seeking a lighter workload, exacerbates the shortage.

PMID- 20131620
TI  - By the numbers. Largest medical group practices.

PMID- 20131619
TI  - Still hard to share. PSOs making progress but still face tech hurdles.

PMID- 20131621
TI  - Cuomo combs FAIR grounds. New N.Y Web site offers out-of-network pay rates.

PMID- 20131622
TI  - But that was then. Review of 07 pension data shows strong funding, wide variation
      among states.

PMID- 20131623
TI  - Looking for a pulse. With plans for reform thrown into disarray, lawmakers ponder
      scaling back their ambitions.
AB  - With healthcare reform on deathwatch in Washington, providers, policymakers and
      lobbyists are wondering what comes next. "None of us knows, but we don't view it
      as the end. We view it as a moment that we have to work through, and hopefully
      we'll still be able to do what's right for the patients and the country," says
      Jeff Korsmo, left, Mayo Clinic Health Policy Center.

PMID- 20131624
TI  - Weighing the cost of disaster. Trial could raise stakes for emergency planning.

PMID- 20131625
TI  - ASCs say bring it on. Centers see required reporting as aiding their case.

PMID- 20131626
TI  - Too steep to climb. Proposed meaningful-use regs ask too much, too soon of
      providers.

PMID- 20131627
TI  - By the numbers. Largest academic medical centers.

PMID- 20131628
TI  - No silver lining. Growth in healthcare spending slowed because of the recession
      but continued to outpace the economy.
AB  - While healthcare spending growth slowed in 2008, that isn't good news, according
      to experts. Rather than being able to credit new efficiencies in the system for
      the slowdown, blame the recession. According to Michael Blaszyk, left, of
      Catholic Healthcare West, the CMS figures underscore the need for cost-control
      reforms and calls the continued rise in healthcare as a share of the economy
      unacceptable.

PMID- 20131629
TI  - Money tops the list. Reform also worries hospital execs: ACHE survey.

PMID- 20131630
TI  - Settlement in Buffalo. Erie County agrees to give hospital annual subsidy.

PMID- 20131631
TI  - More changes on the RAC.

PMID- 20131632
TI  - By the numbers. Largest PAC donations--health professionals.

PMID- 20131633
TI  - Returning to health.

PMID- 20131634
TI  - Plans scramble to defend their medical loss ratios.

PMID- 20131636
TI  - Docs paid faster, with fewer claims denied.

PMID- 20131635
TI  - Strict regulatory environment dogs cancer pain management.

PMID- 20131637
TI  - House call revival, digital-style.

PMID- 20131638
TI  - How plans can improve outcomes and cut costs for preterm infant care.

PMID- 20131639
TI  - Not your father's Cadillac plan.

PMID- 20131640
TI  - States collect valuable data on hospital prices and performance.

PMID- 20131641
TI  - Inpatient rehab facilities benefit post-stroke care.

PMID- 20131642
TI  - Episode-of-care payment creates clinical advantages.

PMID- 20131643
TI  - Higher copayments and deductibles delay medical care, a common problem for
      Americans.

PMID- 20131644
TI  - Testing alternatives to prior authorization.

PMID- 20131645
TI  - New anti-asthma treatment smooths muscle in airways.

PMID- 20131646
TI  - Hospital board members trained on Blues' dime.

PMID- 20131647
TI  - Poor in Part D plans face more premiums in 2010.

PMID- 20131648
TI  - Muscle volume, strength, endurance, and exercise loads during 6-month missions in
      space.
AB  - INTRODUCTION: Decrements in muscular strength during long-duration missions in
      space could be mission-critical during construction and exploration activities.
      The purpose of this study was to quantify changes in muscle volume, strength, and
      endurance of crewmembers on the International Space Station (ISS) in the context
      of new measurements of loading during exercise countermeasures. METHODS: Strength
      and muscle volumes were measured from four male ISS crewmembers (49.5 +/- 4.7 yr,
      179.3 +/- 7.1 cm, 85.2 +/- 10.4 kg) before and after long-duration spaceflight
      (181 +/- 15 d). Preflight and in-flight measurements of forces between foot and
      shoe allowed comparisons of loading from 1-g exercise and exercise
      countermeasures on ISS. RESULTS: Muscle volume change was greater in the calf (
      10 to 16%) than the thigh (-4% to -7%), but there was no change in the upper arm
      (+0.4 to -0.8%). Isometric and isokinetic strength changes at the knee (range 
      10.4 to -24.1%), ankle (range -4 to -22.3%), and elbow (range -7.5 to -16.7%)
      were observed. Although there was an overall postflight decline in total work (
      14%) during the endurance test, an increase in postflight resistance to fatigue
      was observed. The peak in-shoe forces during running and cycling on ISS were
      approximately 46% and 50% lower compared to 1-g values. DISCUSSION: Muscle volume
      and strength were decreased in the lower extremities of crewmembers during long
      duration spaceflight on ISS despite the use of exercise countermeasures. in
      flight countermeasures were insufficient to replicate the daily mechanical
      loading experienced by the crewmembers before flight. Future exercise protocols
      need careful assessment both in terms of intensity and duration to maximize the
      "dose" of exercise and to increase loads compared to the measured levels.

PMID- 20131649
TI  - Vestibular evoked myogenic potentials and saccular plasticity in divers.
AB  - INTRODUCTION: Otolith function, which is dependent on linear velocity and
      acceleration, may be expected to change in underwater divers, who are submerged
      in a medium that is denser than air. The purpose of the present study was to
      examine possible changes in the sacculocollic reflex of professional divers and
      to investigate whether there might be diving-induced adaptation of the saccular
      response. METHODS: We used the vestibular evoked myogenic potential (VEMP)
      response to evaluate saccular function in 12 professional divers shortly after a
      dive and after an interval of at least 24 h. The control group consisted of 12
      matched non-divers. Wave latencies and amplitudes, asymmetry ratio, and the
      response threshold were compared between the groups. RESULTS: Statistically
      significant shortening of N23-wave latency was found in the divers compared with
      the control group. The mean +/- SE were 22 +/- 0.1 and 22.1 +/- 0.7 ms early and
      late after a dive in the divers group vs. 24.5 +/- 0.5 ms in the control group.
      No significant differences were found in any of theVEMP parameters between the
      early and late post-dive recordings. DISCUSSION: We suggest that the reduction in
      N23 latency reflects long-term adaptation of the sacculocollic reflex to
      underwater conditions. Increased sensitivity of the reflex is required to
      compensate for the decrease in linear velocity and acceleration, resulting in
      reduced stimulation of the otolith organ.

PMID- 20131650
TI  - Exertional heat illness among overweight U.S. Army recruits in basic training.
AB  - INTRODUCTION: Heat illness has not declined in the U.S. military despite
      preventive measures. The increase in overweight recruits entering the U.S.
      military may lead to an increase in heat-related events. This study compares the
      risk of heat illness among U.S. Army recruits who exceeded body fat standards at
      accession to those who met standards. METHODS: Recruits with excess body fat and
      qualified applicants to the Army were required to take a preaccession fitness
      test during the study period (February 2005 through September 2006). The test
      included a 5-min step test and 1-min push-up challenge, scored as pass or fail.
      Incidence and outpatient usage for heat illness (any heat illness, heat stroke,
      heat exhaustion, and other heat illness) at 90 d of service were compared in 9667
      male recruits of whom 826 had excess body fat and 8841 were qualified. There were
      too few heat events among women for analysis. RESULTS: The incidence odds ratio
      among male recruits with excess body fat compared to qualified male recruits was
      3.63 (95% CI: 1.92, 6.85). Men with excess body fat had an increased incidence of
      heat illness with a rate ratio of 7.25 (95% CI: 4.17, 12.61). DISCUSSION:
      Although there were few heat illness events, the results indicate a significantly
      increased risk of heat illness and outpatient utilization among male recruits
      with excess body fat. It was estimated that approximately 70% of the relative
      risk for heat illnesses in men with excess body fat during basic training was
      associated with exceeding body fat standards. These findings may have
      implications for military accession and training.

PMID- 20131651
TI  - Airline pilots' knowledge and beliefs about over-the-counter medications.
AB  - INTRODUCTION: Toxicological studies of accident pilots frequently find the
      presence of over-the-counter (OTC) drugs. While many of these drugs are approved
      for use while flying, others are not. To better understand how pilots come to use
      unapproved OTC drugs, this study explored psychological and behavioral factors
      that might influence pilots' decisions about using OTC drug products. METHODS:
      There were 216 working airline pilots who completed a survey that probed their 1)
      attitudes toward taking medications; 2) knowledge of OTC medications and the
      pilot-specific rules that govern their usage; 3) perceived pressures in the work
      environment; and 4) use of available information about OTC medications. RESULTS:
      The results characterize pilots as workers who are often highly motivated to
      consider the use of OTC medications, but who lack the knowledge, available
      information, and information-seeking habits to make informed decisions about OTC
      drug usage under the more complicated constraints of a safety-critical job.
      DISCUSSION: Rather than attempt to diminish the perceived appeal of OTC
      medications in the minds of pilots, we argue that pilots must be provided with
      additional guidance when making decisions about OTC drug usage.

PMID- 20131652
TI  - Reliability of the measurement of stroke volume using impedance cardiography
      during acute cold exposure.
AB  - INTRODUCTION: It is well documented that cardiovascular alterations occur during
      acute cold exposure (ACE). Interindividual variability is present, due mainly to
      body size differences, gender, and age. However, no study has evaluated stroke
      volume in the same individual twice in the same ambient conditions (i.e., test
      retest reliability). Impedance cardiography (ICG) has become a popular method to
      acquire hemodynamic data in both clinical and applied physiology settings.
      Further, ICG does not interfere with other dependent variables such as oxygen
      consumption. Therefore, based on the uniqueness of the methodology, we sought to
      test reliability in this technology at 5 degrees C for 65 min on two separate
      occasions. METHODS: Nine young men underwent two 65-min trials of resting ACE,
      separated by at least 72 h. Volunteers were clothed in approximately one layer of
      clothing. Core and skin temperatures, oxygen consumption, and central
      hemodynamics were measured. RESULTS: As expected, core and skin temperature
      decreased while oxygen consumption showed a modest increase over time. In both
      trials, stroke volume significantly increased over time as heart rate decreased.
      There was similarity within subjects and between trials for all variables, as
      assessed via bivariate correlations. CONCLUSION: Cold increased stroke volume and
      decreased heart rate when subjects were pooled together, but each subject
      retained his individuality (minimal interindividual differences). Results suggest
      that impedance cardiography may be a reliable technique to use during acute cold
      exposure.

PMID- 20131653
TI  - Ectopy in trauma patients: cautions for use of heart period variability in
      medical monitoring.
AB  - INTRODUCTION: Heart period variability measurements have been proposed for use in
      early prediction of mortality or the requirement for lifesaving interventions in
      trauma patients. However, the presence of even one ectopic beat (EB) and/or
      electromechanical noise compromises the accurate calculation of heart period
      variability. We tested the hypothesis that ECGs from trauma patients exhibit a
      greater frequency of EBs than healthy human research subjects. METHODS:
      Continuous ECGs were recorded in 20 healthy human subjects at rest, 108 healthy
      human subjects undergoing experimentally induced progressive central hypovolemia
      (via lower body negative pressure, LBNP), and 245 trauma patients. The
      proportions of subjects/patients with at least one EB were identified in each
      group. RESULTS: ECG waveforms from 20% and 18% of healthy human subjects at rest
      or undergoing LBNP, respectively, contained at least one EB. ECG waveforms from
      36% of the trauma patients were found to contain either EBs (35%) or
      electromechanical noise (1%). CONCLUSIONS: A significant number of EBs occur in
      healthy subjects both at rest and during progressive reduction in central blood
      volume, and trauma is associated with a near doubling of this incidence. As both
      EBs ' and noise result in invalid heart period variability calculations, these
      metrics as currently calculated could not be used in approximately 36% of trauma
      patients. The limited use in nearly two of every five trauma patients indicate
      that it is unlikely that continuous heart period variability measurements could
      substantially improve pre-hospital or emergency room decision-support in trauma.

PMID- 20131654
TI  - Ear pain after breathing oxygen at altitude: prevalence and prevention of delayed
      barotrauma.
AB  - INTRODUCTION: Military pilots frequently report ear pain with onset several hours
      after altitude exposure while breathing pure oxygen, but the prevalence of this
      problem is unknown. A similar problem is described in divers after breathing
      hyperbaric oxygen and it is related to the oxygen contained in the middle ear.
      METHODS: In order to assess the prevalence of delayed ear pain after altitude
      exposure and investigate the effectiveness of preventive use of a nasal balloon
      (NB), we studied 88 healthy military jet pilots who were asymptomatic after
      altitude chamber exposure which included 100% oxygen breathing. A group of 44
      subjects received the NB shortly after the chamber and they were advised to use
      it every hour before going to sleep. A control group of 44 subjects was requested
      to perform the Valsalva maneuver alone over the same period. All subjects
      underwent clinical examination by an otolaryngologist and tympanometry just
      before the chamber exposure and again the day after. RESULTS: The day after the
      altitude exposure, 53.4% of subjects reported ear pain. In the treated group,
      61.4% of subjects were free of symptoms, compared to 31.8% in the control group
      (P < 0.01). Tympanogram was abnormal in eight symptomatic subjects and in six
      asymptomatic. CONCLUSION: Our data suggest that in our subjects there is high
      prevalence of delayed ear barotrauma after altitude chamber exposure while
      breathing pure oxygen and the tympanogram may improve the accuracy of the
      diagnosis in asymptomatic subjects. The nasal balloon appears to be effective for
      prevention.

PMID- 20131655
TI  - The ISS flight of Richard Garriott: a template for medicine and science
      investigation on future spaceflight participant missions.
AB  - BACKGROUND: A total of eight commercial spaceflight participants have launched to
      the International Space Station (ISS) on Soyuz vehicles. Based on an older mean
      age compared to career astronauts and an increased prevalence of medical
      conditions, spaceflight participants have provided the opportunity to learn about
      the effect of space travel on crewmembers with medical problems. The 12-d Soyuz
      TMA-13/12 ISS flight of spaceflight participant Richard Garriott included medical
      factors that required preflight intervention, risk mitigation strategies, and
      provided the opportunity for medical study on-orbit. Equally important, Mr.
      Garriott conducted extensive medical, scientific, and educational payload
      operations during the flight. These included 7 medical experiments and a total of
      15 scientific projects such as protein crystal growth, Earth
      observations/photography, educational projects with schools, and amateur radio.
      The medical studies included the effect of microgravity on immune function,
      sleep, bone loss, corneal refractive surgery, low back pain, motion perception,
      and intraocular pressure. CONCLUSION: The overall mission success resulted from
      non-bureaucratic agility in mission planning, cooperation with investigators from
      NASA, ISS, International Partners, and the Korean Aerospace Research Institute,
      in-flight support and leadership from a team with spaceflight and Capcom
      experience, and overall mission support from the ISS program. This article
      focuses on science opportunities that suborbital and orbital spaceflight
      participant flights offer and suggests that the science program on Richard
      Garriott's flight be considered a model for future orbital and suborbital
      missions. The medical challenges are presented in a companion article.

PMID- 20131656
TI  - Giant hepatic hemangioma and cross-fused ectopic kidney in a spaceflight
      participant.
AB  - Commercial spaceflight participants are typically older than traditional
      astronauts and often have medical conditions that make medical certification for
      flight difficult. This case report considers a 43-yr-old spaceflight participant
      who planned a short-duration Soyuz flight to the International Space Station
      (ISS). While he participated in many hazardous activities such as parachuting,
      hang gliding, scuba diving, Antarctic and jungle exploration, and deep sea
      submersible operations, he knew that several of his medical conditions precluded
      serving as a career astronaut. At the time of his initial spaceflight prescreen
      examination, he was known to have previous bilateral photorefractive keratectomy
      (PRK) for myopia and a cross-fused left ectopic kidney that would be
      disqualifying for a career astronaut. During the evaluation for the left single
      cross-fused ectopic kidney, a giant hepatic hemangioma was also discovered. In
      order to medically qualify for flight, the giant hepatic hemangioma was
      surgically removed. This case summary investigat*es the implications of a single
      cross-fused left ectopic kidney and the decision process and treatment
      implications for spaceflight medical certification in an individual with an
      asymptomatic giant hepatic hemangioma.

PMID- 20131657
TI  - Sacral meningocele in a military pilot, presenting during flight.
AB  - This study describes an unusual case of a military pilot with sacral meningocele
      that contained cerebrospinal fluid and presented as episodes of gluteal neuralgia
      during flight. The patient, a 38-yr-old male pilot, had complained of a dull and
      mild low lumbar pain over the previous 10 mo. These pains were exacerbated and
      radiated to the left gluteal region during flight. The patient's history,
      clinical examination, imaging findings, and treatment are reported. CT and MRI
      imaging revealed an unusual case of sacral meningocele (2.2 cm x 3.6 cm X 5.8
      cm). These lesions can progress steadily in size, leading to worsening symptoms
      and potentially requiring surgical management. However, surgery is not indicated
      for stable and asymptomatic lesions not associated with tumors. In our case,
      tactical monitoring was suggested, since no other symptoms appeared. There are
      currently no other reported cases involving pilots, so an individual approach to
      treatment should be taken in accordance with their military health service, the
      potential, risk factors, and depending on the level of acceleration experienced.
      We discuss the pathogenesis, the clinical and radiological findings of this rare
      condition, and note that a spinal cyst is of special interest when occurring in
      pilots since they are exposed to intense accelerations and spinal strain.

PMID- 20131658
TI  - Pneumatic muscle actuator for resistive exercise in microgravity: test with a leg
      model.
AB  - INTRODUCTION: A proof-of-concept demonstration is described in which a DC
      servomotor (simulating the quadriceps of a human operator) rotated a pulley 90
      degrees (simulating knee extension). A pneumatic muscle actuator (PMA) generated
      an opposing force (antagonist) to the rotating pulley. One application of such a
      device is for use in microgravity environments because the PMA is compact,
      simple, and of relatively small mass (283 g). In addition, the operator can set a
      computer-controlled force-level range in response to individual user changes in
      exercise conditioning over time. METHODS: A PMA was used in this study and
      interacted with a DC servomotor. For each trial, the PMA contracted in response
      to internal pressure. An input voltage profile activated the DC servomotor,
      resulting in the following three phases: an isokinetic counterclockwise pulley
      rotation of 90 degrees over 5 s (Phase I), the position was held for 5 s (Phase
      II), and an isokinetic clockwise rotation of 90 degrees over 5 s (Phase III).
      Root mean square error (RMSE) values were used to evaluate the pulley rotation.
      RESULTS: For Phase I, when the PMA pressures (in kPa) were 300, 450, and 575, the
      percent RMSE, respectively, were 5.24, 6.23, and 4.59. For Phase II, the percent
      RMSE were 2.81, 2.57, and 5.63, respectively. For Phase III, the percent RMSE
      were 5.69, 2.63, and 3.30, respectively. DISCUSSION: This study presents a
      demonstration of a PMA device that can enhance exercise by providing a wide range
      of resistive loads.

PMID- 20131659
TI  - Sleep and performance at cabin altitudes.

PMID- 20131660
TI  - Nanoparticle toxicity.

PMID- 20131661
TI  - You're the flight surgeon: bladder cancer.

PMID- 20131662
TI  - Classics in space medicine. Psychological effects of spaceflight.

PMID- 20131663
TI  - Workplace violence is not part of your job.

PMID- 20131664
TI  - Stopping workplace violence.

PMID- 20131665
TI  - ONA's fight against workplace violence.

PMID- 20131666
TI  - Workplace violence legislation.

PMID- 20131667
TI  - What's in a word?

PMID- 20131668
TI  - [Depression--treatment is possible].

PMID- 20131669
TI  - [Safety of cell culture-based influenza vaccines].
AB  - After more than 60 years, the conventional production of influenza vaccines
      employing fertilized chicken eggs has reached its limits - both in terms of
      temporal flexibility and vaccine production volume. This situation is compounded
      by the fact that the present pandemic-driven situation has roughly doubled the
      overall vaccine demand virtually "overnight". Modem cell culture technology has
      significant advantages over the conventional method of manufacturing influenza
      vaccines employing embryonated chicken eggs, and enables manufacturers to respond
      rapidly to the exploding worldwide seasonal and pandemic-driven need for
      influenza vaccines. Recent articles in the popular press claiming that cell
      culture-based influenza vaccines can cause tumours raised uncertainty among
      physicians and the general population, and also discredit officially accepted
      assessments and product licensing by the relevant authorities. The present
      article provides an overview on the cell culture technology and on the safety
      profile of the cells and of the vaccine product.

PMID- 20131670
TI  - [Suppurative chronic otitis media: etiology, diagnosis and therapy].
AB  - The chronic otitis media is defined as a permanent perforation of the drum
      membrane, which does not close by itself, and an inflammatory reaction in the
      mucosa (mucositis) of the middle ear. Two main forms of the chronic otitis media
      are distinct: the suppurative otitis media and the cholesteatoma. The suppurative
      otitis media is often accompanied by secretion into the external ear canal
      (otorrhoe), but "dry ears" are also common. Other frequent, but not obligatory
      symptoms are hearing impairment, tinnitus, and aural pain or pressure. Although
      genetically determined microbial and immunological factors, as well as Eustachian
      tube characteristics, are supposed to be involved in the pathogenesis of chronic
      suppurative otitis media, many aspects of the pathogenesis still need to be
      clarified. Ear microscopy will show the perforation in the drum membrane. Further
      diagnostic tools are audiometry, vestibular testing, radiological examination
      (high-resolution computed tomography) and microbiological investigation. The
      curative treatment for chronic suppurative otitis media is surgery
      (tympanoplasty, i.e. closure of the perforation in the drum membrane and also--if
      necessary--the reconstruction of the ossicular chain), not conservative
      antimicrobial therapy.

PMID- 20131671
TI  - [Diagnosis of thyroid disease].

PMID- 20131672
TI  - [Gingival hyperplasia].
AB  - Gingival hyperplasia is a typical adverse reaction of certain drugs (phenytoin,
      calcium antagonists and cyclosporine). Also oral contraceptives and presumably
      hormone replacement therapy may rarely lead to gingival hyperplasia. By
      differential diagnosis a paraneoplastic syndrome has to be taken into account.
      Drug induced gingival hyperplasia is reversible when the therapy is stopped or
      modified. If a change of medication is not possible oral hygiene and prophylaxis
      is critical.

PMID- 20131673
TI  - [Proton pump inhibitors and calcium absorption?].

PMID- 20131674
TI  - Human resources. Turn around destructive behaviour.

PMID- 20131675
TI  - Legal. It pays to check for eligibility.

PMID- 20131676
TI  - New in vitro and in situ evidence for a toothpaste formulated for those at risk
      from erosive tooth wear.

PMID- 20131677
TI  - Inhibition of enamel erosion and promotion of lesion rehardening by fluoride: a
      white light interferometry and microindentation study.
AB  - OBJECTIVE: The primary aim of the present in vitro studies was to investigate
      fluoride as an inhibitor of citric acid-mediated demineralization of human enamel
      and promoter of lesion repair using a combination of white light interferometry,
      scanning electron microscopy, and microindentation. Secondary aims included
      investigation of the importance of brushing on bulk tissue loss, and comparison
      of the relative efficacy of commercially available toothpastes on inhibiting
      enamel surface softening and rehardening of incipient erosive lesions. METHODS:
      Resin-mounted polished enamel specimens were prepared from extracted human molars
      and pre-molars. Mean surface roughness (Sa) and bulk tissue loss following
      exposure to an erosive challenge, or an erosive challenge plus brushing were
      investigated using a MicroXAM ADE PhaseShift white light interferometer. Surface
      morphology was determined using a Zeiss Evo 50 scanning electron microscope
      (SEM). The utility of fluoride-based treatments to protect against subsequent
      acid demineralization and to promote remineralization of pre-formed incipient
      lesions was determined using microindentation-based enamel surface softening and
      enamel lesion rehardening models. RESULTS: Treating human enamel specimens with
      Sensodyne Pronamel conferred a clear protective benefit against a subsequent 300
      second citric acid challenge as evidenced by the interferometry and SEM data. The
      increase in Sa and bulk tissue loss caused by an erosive challenge followed by
      brushing was markedly reduced by pre-treatment with sodium fluoride (NaF) in a
      concentration-dependent manner. Sensodyne Pronamel statistically outperformed
      Colgate Sensitive Enamel Protect both in the enamel surface softening model and
      lesion rehardening model, and conferred statistically superior enamel fluoride
      uptake. Treatment of erosive lesions with Sensodyne Pronamel resulted in
      statistically superior rehardening versus two Crest Pro-Health formulations
      containing stannous fluoride (SnF2) and sodium hexametaphosphate (NaHMP); the
      latter did not differ significantly from the fluoride-free negative control
      paste. Sensodyne Pronamel exhibited statistically significant superiority in a
      human saliva-based lesion rehardening model compared to Zendium Sensitive
      containing nominally comparable concentrations of NaF, as well as Colgate
      Sensitive and Colgate Sensitive Multi Protection containing sodium
      monofluorophosphate (NaMFP). CONCLUSION: The utility of NaF, whether delivered
      from simple solution or toothpaste, to reduce citric acid-mediated surface
      roughening and bulk tissue loss has been clearly demonstrated. The effectiveness
      of Sensodyne Pronamel as an anti-erosion toothpaste has also been demonstrated in
      various microhardness models. Crest Pro-Health toothpastes containing SnF2 and
      NaHMP were not statistically differentiable from a fluoride-free control paste in
      the lesion rehardening model. The latter result indicates that the benefit of
      fluoride to promote mineral formation is outweighed by the effect of NaHMP as a
      mineralization inhibitor in this model.

PMID- 20131678
TI  - Fluoride penetration from toothpastes into incipient enamel erosive lesions
      investigated using dynamic secondary ion mass spectrometry.
AB  - OBJECTIVE: The primary aim of this study was to assess the utility of dynamic
      secondary ion mass spectrometry (DSIMS) as a convenient and sensitive technique
      for determining fluoride uptake and distribution into incipient human enamel
      erosive lesions in vitro. A secondary aim was to correlate the extent of lesion
      rehardening following treatment with a toothpaste slurry, with relative fluoride
      uptake determined by DSIMS. The final aim was to compare fluoride uptake by
      incipient lesions treated with toothpastes containing different sources of
      fluoride using DSIMS. METHODS: Relative fluoride uptake into the surface and body
      of enamel erosive lesions was monitored by DSIMS as a function of fluoride
      concentration in a series of formulation-matched experimental pastes. Fluoride
      uptake into lesions that had been subjected to treatment with different
      toothpaste slurries in a single-treatment enamel lesion rehardening model was
      also determined, and its relationship with regard to the extent of rehardening
      and also the fluoride source investigated. RESULTS: Fluoride uptake by incipient
      erosive lesions treated with toothpastes containing NaF was quantitatively
      compared by DSIMS and found to be directly proportional to the fluoride
      concentration over the studied range (0-1400 ppm). Lesion repair observed in a
      single-treatment lesion rehardening model was positively correlated with the
      extent of fluoride uptake by the treated lesions. DSIMS was also able to show
      differences between commercial toothpastes containing different sources of
      fluoride and their ability to deliver the fluoride into the body of the lesion.
      The detrimental effect of sodium hexametaphosphate (NaHMP) present in Crest Pro
      Health formulations previously reported in the single-treatment lesion
      rehardening model was also evident from the DSIMS elemental line scans obtained
      from the lesion cross-sections. CONCLUSION: DSIMS has been shown to be a powerful
      selective technique for quantifying relative fluoride uptake into enamel erosive
      lesions, and determining the extent and depth of lesion penetration. The relative
      efficacy of toothpastes containing fluoride from a variety of sources in the
      single-treatment lesion rehardening study is positively correlated with fluoride
      uptake and penetration determined by DSIMS.

PMID- 20131679
TI  - Evaluation of different fluoridated dentifrice formulations using an in situ
      erosion remineralization model.
AB  - OBJECTIVE: The objective of these three clinical in situ studies was to
      investigate the relative performance of commercially available and experimental
      dentifrice formulations, having different fluoride sources and excipient
      ingredients, at remineralizing a bovine enamel surface previously softened by a
      dietary acid challenge. METHODS: Each study utilized the same randomized, placebo
      controlled, single-blind, crossover design. Subjects undertook single brushings
      of their natural teeth, with an in situ appliance in place, using different
      dentifrices in a randomly assigned order. Study A involved 58 subjects with the
      following dentifrices: Sensodyne Pronamel (1450 ppm F as NaF/5% KNO3); Blend-a
      Med Classic (1450 ppm F as NaF); and a matched (Pronamel) placebo control (0 ppm
      F). Study B involved 56 subjects with the following dentifrices: Sensodyne
      Pronamel (1150 ppm F as NaF/5% KNO3); Crest Cavity Protection (1100 ppm F as
      NaF); Crest Pro-Health (0.454% SnF2 [1100 ppm F]/sodium hexametaphosphate); and a
      matched (Pronamel) placebo control (0 ppm F). Study C involved 56 subjects with
      the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3);
      Sensodyne Pronamel Gentle Whitening (1150 ppm F as NaF/5% KNO3); Colgate
      Sensitive Multi Protection (1000 ppm F as NaMFP/5.53% potassium citrate/2% zinc
      citrate); and a matched (Pronamel) placebo control (0 ppm F). Subjects wore their
      palatal appliances holding eight bovine enamel blocks, previously exposed for 25
      minutes to an in vitro erosive challenge with grapefruit juice, for the duration
      of the experiment. Five minutes after appliance insertion, subjects undertook a
      supervised, 90-second brush/rinse regimen with their assigned dentifrice. Surface
      microhardness (SMH) of the specimens was determined prior to the erosive
      challenge (baseline), after the in vitro erosive challenge, and were remeasured
      after four hours in situ remineralization following the tooth brushing event.
      Finally, SMH values were determined after a second in vitro erosive challenge at
      the end of the in situ remineralization period. Statistical analyses included
      ANOVA and pair-wise comparisons between treatments, testing at a 5% significance
      level. RESULTS: All three studies demonstrated significantly greater percent
      surface microhardness recovery (% SMHr) and percent relative erosion resistance
      (% RER) for dentifrices containing sodium fluoride compared to placebo controls.
      Overall, significantly greater % SMHr (p < 0.0001) was observed for Sensodyne
      Pronamel compared to Blend-a-Med Classic, Crest Pro-Health, and Colgate Sensitive
      Multi Protection dentifrices. Similarly, Sensodyne Pronamel delivered
      directionally better % RER vs. Blend-a-Med Classic (p = 0.0731), and
      significantly higher % RER vs. Crest Pro-Health (p = 0.0074) and Colgate
      Sensitive Multi Protection (p <0.0001). Crest Cavity Protection demonstrated
      significantly better % RER (p = 0.031) than Crest Pro-Health, which in turn
      demonstrated significantly better % RER than the placebo control (p < 0.0001). No
      other statistically significant between-product comparisons were observed.
      CONCLUSION: The results of these in situ studies support the effectiveness of
      dentifrices containing sodium fluoride to reharden enamel previously softened
      with an erosive challenge. Furthermore, these studies demonstrate the protective
      effects conferred to enamel, from erosion following the remineralization process
      in the presence of "ionic" fluoride. Under clinically relevant conditions,
      Sensodyne Pronamel and Sensodyne Pronamel Gentle Whitening offered superior anti
      erosion performance compared to currently marketed dentifrice controls. These
      studies reinforce previous research indicating the importance of formulation
      effects on the relative remineralization performance of dentifrices under erosive
      conditions.

PMID- 20131680
TI  - Formulation considerations for developing toothpastes suitable for those at risk
      from erosive tooth wear.

PMID- 20131681
TI  - HIN1 vaccine shortage and distribution mismanagement.

PMID- 20131682
TI  - By increasing our commitment to professionalism, we can do better.

PMID- 20131683
TI  - Professionalism: a 'critical care' component in health care reform.

PMID- 20131684
TI  - Creating an atmosphere of respect.

PMID- 20131685
TI  - Social determinants of smoking among Hmong Americans residing in Wisconsin.
AB  - OBJECTIVE: This study examined correlates of tobacco use among Hmong people
      residing in Wisconsin. METHODS: Surveys of youth (ages 12-17) and adults (ages >
      or =18), available in English and Hmong, were distributed in 14 communities
      through Hmong Mutual Assistance Associations and analyzed centrally. Surveys
      assessed daily and ever use of tobacco, as well as other sociodemographic
      characteristics. RESULTS: Of those contacted, 2856 people completed the survey
      (1460 youth and 1396 adults). Among youth, 15% reported daily use (18.8% for
      males, 11.7% for females); 32% reported ever use (36.3% for males, 28.2% for
      females). Education and birth location were significant predictors of tobacco
      use. Youth who reported someone in their household smoked were more likely to use
      tobacco. The odds of ever use of tobacco increased as the percent of life lived
      in the United States increased (OR = 3.7). Among adults, prevalence of daily use
      was 20% (25.3% for males, 12.4% for females) and ever use was 35.9% (45% for
      males, 23.2% for females.) Adults born in the United States were 3.4 to 3.7 times
      more likely to use tobacco. The less education reported, the more likely they
      were to be a daily tobacco user. Adults who reported that someone in their
      household smoked were 2.8 to 3.4 times more likely to use tobacco. CONCLUSION:
      Overall, Hmong males are at higher risk of smoking than females, although this
      difference is smaller for youth than adults. Education and household exposure are
      strong predictors of smoking prevalence.

PMID- 20131686
TI  - Travel-associated Dengue illnesses among Wisconsin residents, 2002-2008.
AB  - INTRODUCTION: Dengue infections in humans can result in self-limited illness or
      conditions that can be severe and life-threatening. Persons traveling to many
      tropical regions are at risk for dengue infection. This report retrospectively
      summarizes travel-associated dengue cases occurring among Wisconsin residents
      from 2002 through 2008. METHODS: We used a surveillance case definition based on
      the Centers for Disease Control and Prevention (CDC) 1996 dengue illness case
      definition. Detection of dengue-specific IgM antibody in serum specimens was used
      for laboratory confirmation of dengue. Clinical and travel histories, mosquito
      exposure, and repellent use were obtained from patients by interview using
      arbovirus-specific data collection forms. RESULTS: During 2002-2008, 32 travel
      associated dengue illnesses were reported among Wisconsin residents; none met the
      case criteria of dengue hemorrhagic fever or dengue shock syndrome. Fever (100%),
      headache (90%), and myalgia (87%) were the most frequently reported signs and
      symptoms. Nine (28%) patients were hospitalized; no deaths occurred. Onsets in 25
      (81%) of 31 patients with reported travel histories occurred after return to
      Wisconsin. Eighteen (56%) of the 32 patients were female; median age was 35.5
      years (range 12 to 68 years). Patients most frequently reported travel to
      Mexico/Central America (45%) or the Caribbean Islands (39%). Cases occurred
      during all months. Reported mosquito exposure was high among patients (85%), but
      consistent repellent use was low (6%). CONCLUSIONS: Dengue illnesses occur in
      travelers to dengue-endemic tropical areas. Travelers to these areas must take
      precautions to prevent mosquito bites. Clinicians should consider dengue in
      travelers who develop febrile illnesses with headache or myalgia within 2 weeks
      of their return. Arboviral diseases, including dengue, are reportable in
      Wisconsin.

PMID- 20131687
TI  - The Wisconsin Network for Health Research (WiNHR): a statewide, collaborative,
      multi-disciplinary, research group.
AB  - In response to the goals of the Wisconsin Partnership Program and the National
      Institutes of Health (NIH) Initiatives to Improve Healthcare, the Wisconsin
      Network for Health Research (WiNHR) was formed. As a collaborative, multi
      disciplinary statewide research network, WiNHR encourages and fosters the
      discovery and application of scientific knowledge for researchers and
      practitioners throughout Wisconsin. The 4 founding institutions--Aurora Health
      Care/Center for Urban Population Health (CUPH), Gundersen Lutheran Medical
      Foundation, Marshfield Clinic Research Foundation, and the University of
      Wisconsin-Madison--representing geographically diverse areas of the state, are
      optimistic and committed to WiNHR's success. This optimism is based on the
      relevance of its goals to public health, the quality of statewide health care
      research, and, most importantly, the residents of Wisconsin who recognize the
      value of health research.

PMID- 20131688
TI  - A case of newly diagnosed metastatic pancreatic cancer presenting with associated
      immune thrombocytopenic purpura.
AB  - Metastatic pancreatic adenocarcinoma presenting with immune thrombocytopenic
      purpura is a very rare association. To date, only 1 case report found in the
      literature delineates such an association. We present a case of a patient with
      newly diagnosed, biopsy-proven metastatic pancreatic adenocarcinoma with new
      onset immune thrombocytopenic purpura. The patient's platelet count returned to
      normal limits after being treated with oral corticosteroid therapy. In
      conclusion, immune thrombocytopenic purpura can be associated with metastatic
      pancreatic adenocarcinoma and responds well to corticosteroid therapy.

PMID- 20131689
TI  - Marrow suppression with myelodysplastic features, hypoerythropoetinemia, and
      lipotrophic proptosis due to rosiglitazone.
AB  - Thiazolidinediones (TZDs) are frequently used pharmacotherapeutics for type II
      diabetes mellitus, which exert their effect through peroxisomal proliferator
      agonist receptor (PPAR) mediated increased insulin sensitivity. TZDs are known to
      cause marrow suppression and to stimulate adipogenesis. Case and cohort studies
      show TZDs worsen thyroid-associated orbitopathy. We present a case consistent
      with earlier reports of marrow suppressive pancytopenia manifesting as
      myelodysplastic syndrome, a new implication of hypoerythropoetinemia, and non
      Graves'-associated proliferative proptosis.

PMID- 20131690
TI  - 2009 Physician Citizen of the Year combines service, medicine, and faith.

PMID- 20131691
TI  - The Collaborative Center for Health Equity: a strategic priority at the UW School
      of Medicine and Public Health.

PMID- 20131692
TI  - Recent Wisconsin Supreme Court decision impacts noncompetition agreements.

PMID- 20131693
TI  - It's all about the cost.

PMID- 20131694
TI  - Health care and politics 101.

PMID- 20131695
TI  - Health care for all? Promises, promises.

PMID- 20131696
TI  - Health care payment reform.

PMID- 20131697
TI  - "Focus" will be key for MAG in 2010 state legislative session.

PMID- 20131698
TI  - The effect of current Supreme Court cases on Georgia's tort reform.

PMID- 20131699
TI  - Health care reform's impact on health care fraud enforcement.

PMID- 20131700
TI  - A case of not reading the chart and ineffective hand off communication.

PMID- 20131701
TI  - Twitter, the lost years and the geeks.

PMID- 20131702
TI  - The benefits of being part of a professional nursing organization.

PMID- 20131703
TI  - The ripple effect.

PMID- 20131704
TI  - Life leads the way to a nursing career for Amy Vyhlidal. Interview by Lauren
      Swain.

PMID- 20131705
TI  - Envisioning a future of nurse leaders in the boardroom.

PMID- 20131706
TI  - Building your personal power base as a student and new nurse.

PMID- 20131707
TI  - The changing faces of nursing: a personal story.

PMID- 20131708
TI  - Theories of nursing: a student's vantage point.

PMID- 20131709
TI  - Canadian Healthcare Safety Symposiums.

PMID- 20131710
TI  - Safe positioning for neurosurgical patients.
AB  - Positioning the patient for surgery is an important part of perioperative nursing
      care that should not be underemphasized. The combined factors of time, mechanical
      pressure, and immobility increase the risk of tissue damage. The objectives of
      perioperative positioning activities are to balance optimal surgical exposure
      with the prevention of any injury related to position and to maintain normal body
      alignment without excess flexion, extension, or rotation. After providing general
      principles of positioning, specific considerations with surgical rationale are
      presented for each of the commonly used neurosurgical positions (eg. supine, knee
      chest, prone, lateral, park-bench, sitting).

PMID- 20131711
TI  - Will you help to "do the ask"?

PMID- 20131712
TI  - Pain, dignity and death.

PMID- 20131713
TI  - Oral pathology quiz 65. Case number 1. Parulis.

PMID- 20131714
TI  - Oral pathology quiz 65. Case number 2. Lichenoid mucositis.

PMID- 20131715
TI  - A primer on dental partnerships.

PMID- 20131716
TI  - Update on dental establishments in New Jersey.

PMID- 20131717
TI  - "Thin is in" the art of minimal & no prep veneer.

PMID- 20131718
TI  - FQHCs are successful, progressive.

PMID- 20131719
TI  - The Michigan Board of Dentistry.

PMID- 20131720
TI  - A practice purchaser's continued use of a retired seller's name.

PMID- 20131721
TI  - Independent contractors: new rules, new regulations, new liabilities.

PMID- 20131722
TI  - Strained relationships between general dentists and specialists.

PMID- 20131723
TI  - Health savings accounts: a great idea for 2010.

PMID- 20131725
TI  - Pediatric oral health: our responsibility.

PMID- 20131724
TI  - Examining your office's continuing education policy.

PMID- 20131726
TI  - An update on dental sealants: the effectiveness of various techniques, proper use
      and placement, and concern for safety of materials.

PMID- 20131727
TI  - Current pulp therapy options for primary teeth.
AB  - Pulp therapy options in the primary dentition remain an area of debate and
      research. Current treatment options offer the ability to maintain many primary
      molars and prevent damage to the developing dentition. Proper diagnosis of the
      status of the primary pulp is essential to help the clinician chose the therapy
      that is most indicated for each child. It is important for clinicians to be
      familiar with current trends in this critical area of children's dentistry.

PMID- 20131728
TI  - Facts about fluoride and its use in dentistry.

PMID- 20131729
TI  - Passion.

PMID- 20131730
TI  - Jimson weed abuse in an Oklahoma teen.
AB  - Jimson weed, a plant often abused by teenagers and young adults, grows wild
      throughout Oklahoma. It is best known for its hallucinogenic properties; however
      intoxication can lead to anticholinergic manifestations that are potentially
      dangerous. Over the past six years, sixty-three individuals in Oklahoma have been
      hospitalized for jimson weed intoxication, including this Oklahoma teen.
      Importance lies in proper identification, understanding, and management in
      persons presenting with jimson weed poisoning.

PMID- 20131731
TI  - Hepatocellular carcinoma: status in the era of liver transplantation.

PMID- 20131732
TI  - Budget shortfall creating serious crunch at SoonerCare.

PMID- 20131733
TI  - Gaining in New Orleans. With help from a federal grant, wounded city builds a
      model primary-care system.
AB  - In the wake of Hurricane Katrina, a thriving primary-care network of neighborhood
      clinics in New Orleans seemed unimaginable. But today, thanks to a federal grant,
      the flood-damaged city has built a model system. "From the devastation emerged an
      opportunity to restructure and reorganize primary care for low-income and
      vulnerable populations in New Orleans," says Melinda Abrams, left, of the
      Commonwealth Fund.

PMID- 20131734
TI  - 'Just overwhelming'. Trying to get help to Haiti proves daunting task.

PMID- 20131735
TI  - A watershed moment. Five N. Y. facilities agree to stop dumping drug waste.

PMID- 20131736
TI  - In the spotlight. Media coverage of a hospital's moving day brings rewards as
      well as risks.

PMID- 20131738
TI  - Who takes care of mom? Siblings clash as they respond to parents' aging.

PMID- 20131737
TI  - By the numbers. Most frequently billed Medicare DRGs.

PMID- 20131739
TI  - Advances in psychotherapy for children and adolescents with eating disorders.
AB  - There is a significant lag in the development of evidence based approaches for
      eating disorders in children and adolescents despite the fact that these
      disorders typically onset during these developmental periods. Available studies
      suggest that psychotherapy is the best available approach to these disorders.
      Specific studies support the use of family based interventions, adolescent
      focused individual therapy, and developmentally adapted cognitive behavioral
      therapy in this age group. The current report summarizes the available evidence
      supportive of each of these treatment modalities, as well as, provides a
      description of the rationale and principle therapeutic targets and intervention
      types. Future directions in psychotherapy research in child and adolescent eating
      disorders are discussed.

PMID- 20131740
TI  - The well sibling: challenges and possibilities.
AB  - The impact on the family of a child with serious mental illness or some other
      form of disability has been well documented by many authors. Contributing to this
      impact is society's attitude to mental disabilities, which has been ambivalent
      and marginalizing at best and shunning at worst. Because of this, individuals and
      families dealing with mental disabilities tend to become isolated. Further, onset
      of mental illness often causes disruption of the family's life cycle and
      profoundly affects the sibling relationship. This paper will consider the nature
      of the impact of the ill child on the siblings and propose some ways to address
      and manage the powerful reactions of well siblings in fostering a more satisfying
      individual and family adjustment and in preventing problems for the well sibling
      and future generations.

PMID- 20131741
TI  - The supporting alliance in child and adolescent treatment: enhancing
      collaboration among therapists, parents, and teachers.
AB  - Research indicates that the therapeutic alliance between therapist and pediatric
      patient is most effective in the context of a productive supporting alliance--an
      alliance encompassing the network of relationships among therapists, parents and
      teachers. In this essay, we develop a model of the supporting alliance, arguing
      that the child's primary relationships with various parties (therapists,
      teachers, and parents) imply a set of secondary relationships among those parties
      (parent-therapist, therapist-teacher, parent-teacher). We review the literature
      on these secondary relationships, focusing on their nature and discussing the
      benefits of and obstacles to establishing productive collaborations in each case.
      We also describe three sorts of pathology that can afflict the supporting
      alliance as a whole, and discuss the importance of patient autonomy and therapist
      patient confidentiality relative to the supporting alliance. Finally, we identify
      directions for future research and highlight implications for practice.

PMID- 20131742
TI  - Working with parents: implications for individual psychotherapeutic work with
      children and adolescents.
AB  - Child psychotherapists recognize that working with parents is an indispensable
      part of working individually with child and adolescent patients. Children and
      adolescents are typically referred by their parents or other concerned adults.
      What tends to differ among clinicians is their approach to parents rather than
      the conviction of the importance of the parents' involvement. Historically, it
      was the "child guidance" movement early in the 20th century that initially
      impacted how clinicians work with parents and how this parent work can be
      integrated with individual child work. A different, but equally significant,
      impact came from the field of child psychoanalysis, despite the fact that "parent
      work" had not been the primary interest of its authors. This paper reviews 100
      years of clinical writings in child psychoanalysis, highlighting its legacy for
      modern psychotherapists. In addition, I present several cases that stress the
      parent-child relationship in individual child and adolescent treatment to
      illustrate a clinically flexible approach to involving parents.

PMID- 20131743
TI  - The role of body image in pediatric illness: therapeutic challenges and
      opportunities.
AB  - The body image is the individual's mental representation of his own body, a
      representation that encompasses both perceptual and ideational components. In
      this paper I will explore the concept of body image, its development and its
      relationship to self-image and object relations in children with chronic medical
      illness. From this discussion and with the help of specific cases of medically
      ill children I have treated for a variety of psychological symptoms, I will
      recommend an approach to the assessment and treatment of this challenging group
      of patients.

PMID- 20131744
TI  - Distribution of radiological density in bone regenerate in relation to cyclic
      displacements of bone fragments.
AB  - We asked how bone fragment displacement could influence the distribution of
      radiological density in bone regenerate formed during the process of bone
      lengthening. The metatarsi of 21 sheep were lengthened by 20 mm by the Ilizarov
      method. The bone fragments were externally fixed with a specially designed ring
      external fixator equipped with linear actuator driver system. The test sheep were
      divided into three experimental groups: the G1 and G2 groups (N = 8) and the GR
      group (N = 5)--the reference group. In the case of sheep from the G1 and G2
      groups, the lengthening was supplemented with mechanical stimulation of the
      regenerate in the form of cyclic bone fragment displacements (CBFDs) with the
      amplitudes of 1 mm (G1) and 2 mm (G1). Mechanical stimulation was applied over 30
      days for 1 h per day with a frequency of 1 Hz. Eight weeks after the procedure
      the sheep were sacrificed in accordance with the required procedures. The
      analysis of the degree of bone regenerate mineralization involved the studies
      based on the CT scanning. The analysis of the results obtained is based on the
      paramenter called the degree of regenerate mineralization (RMD). The analysis of
      radiological density was carried out in the selected measurement areas. Such an
      area was located in three horizontal zones, taking into account the regenerate
      height, i.e. in its middle part (half regenerate length); the top part, 2 mm from
      the edge of the proximal fragment; and the bottom part, 2 mm from the edge of the
      distal fragment. The value of the RMD parameter varies significantly, depending
      on the bone regenerate area. The results obtained show that the CBFD = 2 mm
      accelerates the rate of mineralization of an eight-week-old regenerate. In the
      case of CBFD = 1 mm, the mineralization rate is lower by more than a dozen per
      cent.

PMID- 20131745
TI  - Flexibility and trackability of laser cut coronary stent systems.
AB  - Coronary stents are the most important supports in present day cardiology.
      Flexibility and trackability are two basic features of stents. In this paper,
      four different balloon-expandable coronary stent systems were investigated
      mechanically in order to compare their suitability. The coronary stent systems
      were assessed by measurements of stent flexibility as well as by comparison of
      forces during simulated stenting in a self-investigated coronary vessel model.
      The stents were cut by laser from a single tube of 316L stainless steel or L-605
      (CoCr) cobalt chromium alloy. The one-and four-point bending tests were carried
      out to evaluate the stent flexibility E x I (Nmm(2)), under displacement control
      in crimped and expanded configurations. The flexibility of stents would be rather
      dependent on the design than on raw material. In general a more flexible stent
      needs lower tracking force during the implantation. The L-605 raw material stents
      need lower track force to pass through in the vessel model than the 316L raw
      material stents. The sort and long stents passed through the curved vessel model
      in different ways. The long stents nestled to the vessel wall at the outer arc
      and bent, while the short stents did not bend in the curve, only the delivery
      systems bent.

PMID- 20131746
TI  - Interaction of parylene C with biological objects.
AB  - The aim of the present work was to examine the interactions of parylene C with
      such selected biological objects as: blood plasma proteins, platelets,
      endothelial cells, and bacterial biofilm produced by E. coli cells. The results
      obtained strongly support the thesis that parylene C is a material worth
      considering for biomedical use. Parylene C coating on polished medical steel
      significantly reduces platelet adhesion to this surface. On the other hand, in
      the case of the surface of machined medical steel coated with parylene C, the
      number of adhered platelets is significantly higher. This also means that surface
      texture of substrate material is very well reproduced by parylene C coating and
      is an important factor facilitating the platelet adhesion. Adsorption of plasma
      proteins at parylene C surface is very effective, and this finding confirms a
      notion that cell interaction with surfaces is mediated by the adsorbed proteins.
      In the light of the above, a high susceptibility of parylene C surface to
      bacterial colonization is easy to explain. The results showing reduced
      proliferation and changes in endothelial cell gene expression should also be
      seriously analysed when parylene C is considered for the use in contact with
      blood vessels.

PMID- 20131747
TI  - Structural and thermal properties of polypropylene mesh used in treatment of
      stress urinary incontinence.
AB  - Besides material biocompatibility, it is possible to infer that both vaginal and
      urethral erosion rates associated with sub-urethral synthetic slings may be
      related to the mechanical properties of the meshes and also to their other
      properties. With the aim of understanding what distinguishes the different
      polypropylene meshes, used for the treatment of the stress urinary incontinence
      (SUI), their structural and thermal properties were investigated. Five different
      mesh types were tested (Aris, Auto Suture, Avaulta, TVTO and Uretex).
      Differential scanning calorimetry (DSC) and infrared spectroscopy (FTIR) tests
      were performed. Furthermore, geometry (electron microscope), linear density and
      relative density (pyknometer) of the meshes were investigated. The meshes are
      made of the isotactic polypropylene homopolymer. Aris mesh presented the smallest
      fibre diameter, linear density and the level of crystallinity among all the
      meshes used for the treatment of the SUI. This study shows that there is a direct
      relationship between the fibre diameter, linear density, level of crystallinity
      and flexural stiffness of the polypropylene meshes used for the treatment of the
      SUI.

PMID- 20131748
TI  - Influence of loading history on the cervical screw pullout strength value.
AB  - The problem of the loosening and pullout of bone screws in cervical spine
      stabilisation is a significant factor in failed implantations of that spine
      region. Therefore, studies were undertaken to determine the impact of the loading
      history of bone screws of the cervical spine, inserted from the anterior
      approach, on the stability of the screw-bone interface. The research was
      conducted on vertebrae obtained from cadaver specimens of the cervical spine. Two
      screws were inserted into each vertebra and then pulled out with a force acting
      along the screw axis. The mean pullout force for the screws subjected to cyclic
      preloading was 355.2+/-74.4 N, and for the screws subjected to direct pullout it
      was 411.0+/-78 N (p<0.05). The research results show a significant impact of bone
      tissue preloading with a cyclic variable force on the pullout force obtained. For
      the preloaded bone screws the recorded rupture strength of the implant-vertebral
      body interface was by 16% lower compared to the screws pulled out without
      preloading. The values presented also show a strong correlation between the bone
      density and the pullout force obtained after cyclic loading with the strength
      normal to the screw axis.

PMID- 20131749
TI  - Shear bond strength of epoxy resin-based endodontic sealers to bovine dentin
      after ozone application.
AB  - The idea of using ozone to disinfect root canals is of recent origin. The wide
      acceptance of epoxy resin-based sealers lead us to investigate whether ozone can
      influence the adhesion to the dentin. In this study, we tested the shear bond
      strength of AH Plus and EZ Fill. Forty freshly extracted bovine teeth were
      randomly divided into 5 groups. 16 of these samples were treated with ozone for
      60 seconds (HealOzone, Kavo). 8 samples were conditioned with the G Bond bonding
      system. The groups tested were: (1) AH Plus, (2) AH Plus and ozone, (3) EZ Fill,
      (4) EZ Fill and ozone, (5) AH Plus and G Bond. 48 hours after being prepared the
      specimens were tested for shear bond strength. Statistical analysis showed
      significant differences between materials (AH Plus > EZ Fill) and significant,
      positive influence of ozone and bonding agent on the shear bond strength.

PMID- 20131750
TI  - Variations of temperature of acrylic bone cements prepared by hand and vacuum
      mixing during their polymerization.
AB  - The aim of this work was to investigate variations of temperature in acrylic bone
      cement SmartSet HV during its polymerization as the function of mixing technique
      (hand mixing and vacuum mixing) and sample thickness. The temperature of 25-mm
      diameter samples differing in their thickness was monitored using a parallel
      plate measuring system of the compact rheometer preheated to the body
      temperature. The curves representing the temperature measured and average values
      of times needed to obtain the peak temperatures of the test samples prepared by
      different techniques of mixing are presented and discussed. It was found that the
      maximum temperature and also the times of peak temperatures rose with sample
      thickness but at different rate for each technique of mixing.

PMID- 20131751
TI  - Effect of diet on mechanical properties of horse's hair.
AB  - The aim of this research was to assess the effect of diet supplementation with
      zinc and copper, in different chemical forms (organic and inorganic), on the
      mechanical properties of the hair of healthy English thoroughbred horses. Hairs
      were taken from 18 horses which had been fed with oats and hay for a period of
      110 days. Twelve of the horses had been additionally given a daily dose of 700 g
      of highquality 44-ingredients Fohlengold St-Hippolyt muesli made by Muhle Ebert
      Dilheim. Six of them had received the muesli-containing organic zinc and copper
      (OS), while the other six horses had received the muesli-containing inorganic
      zinc and copper (IS). The mechanical properties of the hairs before and after the
      supplementation period were tested in a Synergie 100 (MTS) testing machine. Each
      of the hairs was loaded at a constant rate of 20 mm/min until rupture. Young
      modulus (E), breaking stress (Ru) and yield point (Rs) of the particular hairs
      were determined. No significant changes in the mechanical parameters were
      observed in the reference group in which the horses were fed with only oats and
      hay for the whole experimental period of 110 days. The supplementation of the
      diet with inorganic zinc and copper resulted in an increase in the elasticity and
      diameter of the hairs and in a simultaneous reduction in their strength. Whereas
      organic zinc and copper caused an increase in the elasticity and strength of the
      hairs and a simultaneous reduction in their diameter. It has been shown that the
      organic form of the supplemented trace zinc and copper (mainly copper) elements
      has a beneficial effect on the mechanical properties of the hairs since it
      results in an increase in both their elasticity and strength.

PMID- 20131752
TI  - The necessity of physiological muscle parameters for computing the muscle forces:
      application to lower extremity loading during pedalling.
AB  - The aim of this study is to determine how the use of physiological parameters of
      muscles is important. This work is focused on musculoskeletal loading analysis
      during pedalling adopting two approaches: without (1) and with (2) the use of
      physiological parameters of muscles. The static-optimization approach together
      with the inverse dynamics problem makes it possible to obtain forces in
      individual muscles of the lower extremity. Input kinematics variables were
      examined in a cycling experiment. The significant difference in the resultant
      forces in one-joint and two-joint muscles using the two different approaches was
      observed.

PMID- 20131753
TI  - A dual-labeled knottin peptide for PET and near-infrared fluorescence imaging of
      integrin expression in living subjects.
AB  - Previously, we used directed evolution to engineer mutants of the Ecballium
      elaterium trypsin inhibitor (EETI-II) knottin that bind to alphavbeta3 and
      alphavbeta5 integrin receptors with low nanomolar affinity, and showed that Cy5.5
      or (64)Cu-DOTA-labeled knottin peptides could be used to image integrin
      expression in mouse tumor models using near-infrared fluorescence (NIRF) imaging
      or positron emission tomography (PET). Here, we report the development of a dual
      labeled knottin peptide conjugated to both NIRF and PET imaging agents for
      multimodality imaging in living subjects. We created an orthogonally protected
      peptide-based linker for stoichiometric coupling of (64)Cu-DOTA and Cy5.5 onto
      the knottin N-terminus and confirmed that conjugation did not affect binding to
      alphavbeta3 and alphavbeta5 integrins. NIRF and PET imaging studies in tumor
      xenograft models showed that Cy5.5 conjugation significantly increased kidney
      uptake and retention compared to the knottin peptide labeled with (64)Cu-DOTA
      alone. In the tumor, the dual-labeled (64)Cu-DOTA/Cy5.5 knottin peptide showed
      decreased wash-out leading to significantly better retention (p < 0.05) compared
      to the (64)Cu-DOTA-labeled knottin peptide. Tumor uptake was significantly
      reduced (p < 0.05) when the dual-labeled knottin peptide was coinjected with an
      excess of unlabeled competitor and when tested in a tumor model with lower levels
      of integrin expression. Finally, plots of tumor-to-background tissue ratios for
      Cy5.5 versus (64)Cu uptake were well-correlated over several time points post
      injection, demonstrating pharmacokinetic cross validation of imaging labels. This
      dual-modality NIRF/PET imaging agent is promising for further development in
      clinical applications where high sensitivity and high resolution are desired,
      such as detection of tumors located deep within the body and image-guided
      surgical resection. 

PMID- 20131754
TI  - Cross-linking of type I collagen with microbial transglutaminase: identification
      of cross-linking sites.
AB  - Collagen is a popular biomaterial. To deal with its lack of thermal stability and
      its weak resistance to proteolytic degradation, collagen-based materials are
      stabilized via different cross-linking procedures. Regarding the potential
      toxicity of residual cross-linking agents, enzyme-mediated cross-linking would
      provide an alternative and nontoxic method for collagen stabilization. The
      results of this study show that type I collagen is a substrate for mTG. However,
      epsilon-(gamma-glutamyl)lysine cross-links are only incorporated at elevated
      temperatures when the protein is partially or completely denatured. A maximum
      number of 5.4 cross-links per collagen monomer were found for heat-denatured
      collagen. Labeling with the primary amine monodansylcadaverine revealed that at
      least half of the cross-links are located within the triple helical region of the
      collagen molecule. Because the triple helix is highly ordered in its native
      state, this finding might explain why the glutamine residues are inaccessible for
      mTG under nondenaturing conditions.

PMID- 20131755
TI  - New biomarkers for monitoring the levels of isothiocyanates in humans.
AB  - Isothiocyanates (ITCs) found in cruciferous vegetables have demonstrated cancer
      preventive activity in animals, and increased dietary intake of ITCs has been
      shown to be associated with a reduced cancer risk in humans. ITCs exert their
      cancer chemopreventive action by multiple mechanisms, for example, by modulating
      the activities of phase I and phase II drug metabolism enzymes, by inhibiting the
      cell cycle and histone deacetylase, and by causing apoptotic cell death. In
      cells, protein adducts account for most of total cellular ITC uptake at 4 h after
      treatment. The time course of this protein binding correlates well with the
      inhibition of proliferation and the induction of apoptosis. Animal studies have
      shown that glutathione conjugates are the major products of ITCs. The major
      urinary excretion products of ITCs in human are N-acetyl cysteine conjugates.
      Urinary metabolites might provide the exposure history of the last 24 h, if the
      urine of the full next day is collected. However, this is not feasible in large
      epidemiological studies. Furthermore, the mercapturic acids of ITC are not
      stable. Therefore, stable biomarkers are needed that reflect a larger time span
      of the ITC exposure history. We developed a method to determine stable (not
      cysteine adducts) reaction products of ITCs with albumin and hemoglobin in humans
      and mice. We reacted albumin with the ITCs: benzyl isothiocyanate (BITC),
      phenylethyl isothiocyanate (PEITC), sulforaphane (SFN), and allyl isothiocyanate
      (AITC). After enzymatic digestion, we found one major product with lysine using
      LC-MS/MS. The identity of the adducts was confirmed by comparing the analyses
      with synthetic standards: N(6)-[(benzylamino)carbonothioyl]lysine (BITC-Lys),
      N(6)-{[(2-phenylethyl)amino]carbonothioyl}lysine (PEITC-Lys), N(6)-({[3
      (methylsulfinyl)propyl]amino}carbonothioyl)lysine (SFN-Lys), and N(6)
      [(allylamino]carbonothioyl]lysine (AITC-Lys). The adduct levels were quantified
      by isotope dilution mass spectrometry using the corresponding new ITC
      [(13)C(6)(15)N(2)]lysines as internal standards. The applicability of the method
      was tested for biological samples obtained from different experiments. In humans
      consuming garden cress, watercress, and broccoli and/or in mice exposed
      chronically to N-acetyl-S-{[(2-phenylethyl)amino]carbonothioyl}-l-cysteine,
      albumin and hemoglobin adducts were found. BITC-Lys, PEITC-Lys, and SFN-Lys
      released after enzymatic digestion of the proteins were quantified with LC-MS/MS.
      This new method will enable quantification of ITC adducts in blood proteins from
      large prospective studies about diet and cancer. Protein adducts are involved in
      the chemopreventive effects of ITCs. Therefore, blood protein adducts are a
      potential surrogate marker for the effects of ITCs at the cellular level. This
      new technique will improve the assessment of ITC exposure and the power of
      studies on the relationship between ITC intake and cancer.

PMID- 20131757
TI  - Correlation of cell adhesive behaviors on superhydrophobic, superhydrophilic, and
      micropatterned superhydrophobic/superhydrophilic surfaces to their surface
      chemistry.
AB  - A micropatterned superhydrophobic/superhydrophilic surface was successfully
      fabricated by plasma CVD and VUV irradiation. Physicochemical properties of the
      superhydrophobic, superhydrophilic, and superhydrophobic/superhydrophilic
      surfaces were investigated. The roughness structures on the superhydrophilic
      surface remained intact compared to those of the superhydrophobic surface. The
      micropatterned superhydrophobic/superhydrophilic surface was used as a scaffold
      of cell culture. On the micropatterned surface, the cells attached to the
      superhydrophilic regions in a highly selective manner, forming circular
      microarrays of the cells corresponding to the pattern. On the micropatterned
      surface with pattern distances of 200 microm between superhydrophilic regions,
      the cells adhered on the superhydrophilic regions and partly extended to the
      neighboring cells. In contrast, when the pattern distances between the
      superhydrophilic regions were more than 400 microm, the cells did not extend to
      the neighboring cells. Cell adhesion behaviors on superhydrophobic and
      superhydrophilic surfaces were also examined. The cells adhered and proliferated
      on both superhydrophobic and superhydrophilic surfaces. However, on the
      superhydrophobic surface, constant contact to facilitate cell division and
      proliferation was required. On the other hand, the cells easily adhered and
      proliferated on the superhydrophilic surface immediately after seeding. These
      differences in cell adhesion behavior induced site-selective cell adhesion on the
      superhydrophilic regions. Furthermore, protein adsorption behavior that plays an
      important role in cell adhesion on flat hydrophobic and hydrophilic surface was
      also examined. The amounts of the protein adsorption on the flat hydrophilic
      surface were much greater than those on the flat hydrophobic surface.

PMID- 20131756
TI  - Formulation of a peptide nucleic acid based nucleic acid delivery construct.
AB  - Gene delivery biomaterials need to be designed to efficiently achieve nuclear
      delivery of plasmid DNA. Polycations have been used to package DNA and other
      nucleic acids within submicrometer-sized particles, offering protection from
      shear-induced or enzymatic degradation. However, cytotoxicity issues coupled with
      limited in vivo transfection efficiencies minimize the effectiveness of this
      approach. In an effort to improve upon existing technologies aimed at delivering
      nucleic acids, an alternative approach to DNA packaging was explored. Peptide
      nucleic acids (PNAs) were used to directly functionalize DNA with poly(ethylene
      glycol) (PEG) chains that provide a steric layer and inhibit multimolecular
      aggregation during complexation. DNA prePEGylation by this strategy was predicted
      to enable the formation of more homogeneous and efficiently packaged polyplexes.
      In this work, DNA-PNA-peptide-PEG (DP3) conjugates were synthesized and self
      assembled with 25 kDa poly(ethylenimine) (PEI). Complexes with small standard
      deviations and average diameters ranging 30-50 nm were created, with minimal
      dependence of complex size on N/P ratio (PEI amines to DNA phosphates).
      Furthermore, PEI-DNA interactions were altered by the derivatization strategy,
      resulting in tighter compaction of the PEI-DP3 complexes in comparison to PEI-DNA
      complexes. Transfection experiments in Chinese hamster ovary (CHO) cells revealed
      comparable transfection efficiencies but reduced cytotoxicities of the PEI-DP3
      complexes relative to PEI-DNA complexes. The enhanced cellular activities of the
      PEI-DP3 complexes were maintained following the removal of free PEI from the PEI
      DP3 formulations, whereas the cellular activity of the conventional PEI-DNA
      formulations was reduced by free PEI removal. These findings suggest that DNA
      prePEGylation by the PNA-based strategy might provide a way to circumvent
      cytotoxicity and formulation issues related to the use of PEI for in vivo gene
      delivery. 

PMID- 20131758
TI  - Peptide-targeted Nanoglobular Gd-DOTA monoamide conjugates for magnetic resonance
      cancer molecular imaging.
AB  - Effective imaging of a cancer molecular biomarker is critical for accurate cancer
      diagnosis and prognosis. CLT1 peptide was observed to specifically bind to the
      fibrin-fibronectin complexes presented in tumor extracellular matrix. In this
      study, we synthesized and evaluated CLT1 peptide-targeted nanoglobular Gd-DOTA
      monoamide conjugates for magnetic resonance (MR) imaging of the fibrin
      fibronectin complexes in tumor. The targeted nanoglobular contrast agents were
      prepared by conjugating peptide CLT1 to G2 and G3 nanoglobule (lysine dendrimers
      with a cubic silsesquioxane core) Gd-DOTA monoamide conjugates via click
      chemistry. The T(1) relaxivities of peptide-targeted G2 and G3 nanoglobules were
      7.92 and 8.20 mM(-1) s(-1) at 3T, respectively. Approximately 2 peptides and 25
      Gd-DOTA chelates were conjugated onto the surface of 32 amine groups of G2
      nanoglobule, and 3 peptides and 43 Gd-DOTA chelates onto the surface of 64 amine
      groups of G3 nanoglobule. The peptide-targeted nanoglobular contrast agents
      showed greater contrast enhancement than the corresponding nontargeted agents in
      tumor at a dose of 0.03 mmol-Gd/kg in female athymic mice bearing MDA-MB-231
      human breast carcinoma xenografts. The targeted MRI contrast agents have a
      potential for specific cancer molecular imaging with MRI.

PMID- 20131759
TI  - Another paradigm in solvent extraction-based microencapsulation technologies.
AB  - The objectives of this study were to apply a base-driven reaction to developing a
      new microencapsulation technique to prepare progesterone-containing poly-D,L
      lactide-co-glycolide microspheres. Nonhalogenated ester solvents such as ethyl
      acetate and ethyl formate were used as dispersed solvents. After an oil-in-water
      emulsion was prepared, a sodium hydroxide solution was added to trigger base
      catalyzed hydrolysis of organic solvents dissolved in the aqueous phase. Their
      rapid depletion provided a sink condition and drove the continual diffusion of
      the organic solvents residing in emulsion droplets into the aqueous phase. These
      events led to the solidification of emulsion droplets into microspheres over 15
      30 min, without the use of a quenching liquid. The rate of the base-driven
      reaction observed with ethyl formate was 2.3 times faster than that attained with
      ethyl acetate. The drug encapsulation efficiency was >or=93.2%, and solvent
      residues in the microspheres ranged from 1.87 to 2.69%. GPC and FTIR results
      demonstrated that the structural integrity of the polymer and progesterone
      remained unchanged during the base-catalyzed microencapsulation process. This
      method might serve as a promising alternative for preparing nanoparticles and
      microspheres.

PMID- 20131760
TI  - Thermodynamics of multivalent interactions: influence of the linker.
AB  - This paper describes a thermodynamic analysis of multivalent interactions, with
      the goal of clarifying the influence of the linker on the enhancement in avidity
      due to multivalency. The use of multivalency represents a promising approach to
      inhibit undesired biological interactions, promote desired cellular responses,
      and control recognition events at surfaces. Several groups have synthesized
      multivalent ligands that are orders of magnitude more potent than the
      corresponding monovalent ligands. A better understanding of the theoretical basis
      for the large enhancements in avidity would help guide the design of more potent
      synthetic multivalent ligands. In particular, there has been significant
      controversy regarding the extent to which the loss of conformational entropy of
      the linker influences the enhancement in avidity due to multivalency. To help
      clarify this issue, we present the thermodynamic analysis of a heterodivalent
      ligand-receptor interaction. Our analysis helps reconcile seemingly competing
      theoretical analyses of multivalent binding. Our results indicate that the
      dependence of the free energy of multivalent binding on linker length can be weak
      even if there is a significant decrease in the conformational entropy of the
      linker on binding. Our results are also consistent with studies demonstrating
      that the use of flexible linkers represents an effective strategy to design
      potent multivalent ligands.

PMID- 20131761
TI  - Probing asphaltene aggregation in native crude oils with low-field NMR.
AB  - We show that low-field proton nuclear magnetic resonance (NMR) relaxation and
      diffusion experiments can be used to study asphaltene aggregation directly in
      crude oils. Relaxation was found to be multiexponential, reflecting the
      composition of a complex fluid. Remarkably, the relaxation data for samples with
      different asphaltene concentrations can be collapsed onto each other by a simple
      rescaling of the time dimension with a concentration-dependent factor xi, whereas
      the observed diffusion behavior is unaffected by asphaltene concentration. We
      interpret this finding in terms of a theoretical model that explains the enhanced
      relaxation by the transitory entanglement of solvent hydrocarbons within
      asphaltene clusters and their subsequent slowed motion and diffusion within the
      cluster. We relate the measured scaling parameters xi to cluster sizes, which we
      find to be on the order of 2.2-4.4 nm for an effective sphere diameter. These
      sizes are in agreement with the typical values reported in the literature as well
      as with the small-angle X-ray scattering (SAXS) experiments performed on our
      samples.

PMID- 20131762
TI  - Active ester functional single core magnetic nanostructures as a versatile
      immobilization matrix for effective bioseparation and catalysis.
AB  - Multifunctional nanocarriers for amino functional targets with a high density of
      accessible binding sites are obtained in a single polymerization step by grafting
      from copolymerization of an active ester monomer from superparamagnetic cores. As
      a result of the brush-like structure of the highly dispersed shell, the nano
      objects exhibit an available capture capacity for amines that is found to be up
      to 2 orders of magnitude higher than for commercial magnetic beads, and the
      functional brush shell can serve as a template for many types of pendant
      functional groups and molecules. As comonomer, oligo(ethylene glycol)
      methacrylate allows for excellent water solubility at room temperature,
      biocompatibility, and thermoflocculation. We demonstrate the biorelated
      applicability of the hybrid nanoparticles by two different approaches. In the
      first approach, the immobilization of trypsin to the core-shell nanoparticles
      results in highly active, nanoparticulate biocatalysts that can easily be
      separated magnetically. Second, we demonstrate that the obtained nanoparticles
      are suitable for the effective labeling of cell membranes, opening a novel
      pathway for the easy and effective isolation of membrane proteins.

PMID- 20131763
TI  - Potential energy surfaces fitted by artificial neural networks.
AB  - Molecular mechanics is the tool of choice for the modeling of systems that are so
      large or complex that it is impractical or impossible to model them by ab initio
      methods. For this reason there is a need for accurate potentials that are able to
      quickly reproduce ab initio quality results at the fraction of the cost. The
      interactions within force fields are represented by a number of functions. Some
      interactions are well understood and can be represented by simple mathematical
      functions while others are not so well understood and their functional form is
      represented in a simplistic manner or not even known. In the last 20 years there
      have been the first examples of a new design ethic, where novel and contemporary
      methods using machine learning, in particular, artificial neural networks, have
      been used to find the nature of the underlying functions of a force field. Here
      we appraise what has been achieved over this time and what requires further
      improvements, while offering some insight and guidance for the development of
      future force fields.

PMID- 20131764
TI  - Free energy calculations on disulfide bridges reduction in proteins by combining
      ab initio and molecular mechanics methods.
AB  - Free energy profiles were calculated for the reduction of the four disulfide
      bridges in lysozyme by tris(2-carboxyethyl)phosphine (TCEP). The computational
      method combines high-precision density functional theory (DFT) calculations
      performed on the core of the reactant system with classical mechanical free
      energy evaluations based on the sampling of the configuration space of reaction
      environment. The predicted reaction energy barriers are in satisfactory agreement
      with experimental data, proving that the present method provides a reliable
      description of the mechanism of reaction. The role of the protein environment in
      this mechanism is further emphasized by analyzing the different contributions to
      the free energy profiles. It is shown that the protein environment affects the
      reaction by three factors: polarizability, steric hindrance of the reactant site,
      and S-S bridge distortion due to structural constraints. The corresponding
      effects are quantitatively evaluated, and the results are discussed in connection
      with the current two-step reaction model for the reduction of S-S bridges in
      proteins.

PMID- 20131765
TI  - Domino Heck-aza-Michael reactions: efficient access to 1-substituted tetrahydro
      beta-carbolines.
AB  - A simple and efficient palladium-catalyzed domino reaction for the synthesis of a
      series of C1-substituted tetrahydro-beta-carbolines is described. This domino
      process involves a Heck reaction at the indole 2-position of a halogenated
      tryptamine precursor, followed by intramolecular aza-Michael addition.

PMID- 20131766
TI  - Rigid pillars and double walls in a porous metal-organic framework: single
      crystal to single-crystal, controlled uptake and release of iodine and electrical
      conductivity.
AB  - A highly stable pillared and double-walled zinc(II) metal-organic framework with
      regular nanochannels displays single-crystal to single-crystal transformation
      upon desolvation and a large quantity of iodine uptake, controlled release, and
      electrical conductivity elevation due to synergy between the iodine guests and
      the host framework.

PMID- 20131767
TI  - Anthracene-BODIPY dyads as fluorescent sensors for biocatalytic Diels-Alder
      reactions.
AB  - Fluorescence spectroscopy is a powerful, extremely sensitive technique for the
      investigation of enzyme and ribozyme mechanisms. Herein, we describe the
      synthesis and characterization of water-soluble fluorescence probes for studying
      biocatalytic Diels-Alder reactions. These probes consist of anthracene and
      sulfonated BODIPY fluorophores fused by conjugated phenylacetylenyl bridges.
      Intact anthracene efficiently quenches BODIPY fluorescence, likely by
      photoinduced electron transfer. Upon destruction of the aromatic system by the
      Diels-Alder reaction, the fluorescence emission increases 20-fold. Binding in the
      catalytic pocket of a Diels-Alderase ribozyme yields a further approximately 2
      fold increase in the fluorescence intensity of both the anthracene-BODIPY and the
      Diels-Alder-product-BODIPY probes. Therefore, a fluorescence-based distinction of
      free substrate, bound substrate, bound product, and free product is possible.
      With these all-in-one reporters, we monitored RNA-catalyzed Diels-Alder reactions
      under both single- and multiple-turnover conditions down to the nanomolar
      concentration range. Burst analysis at the single-molecule level revealed
      blinking of the dyads between an on state and an off state, presumably due to
      rotation around the phenylacetylenyl bridge. Binding to the ribozyme does not
      increase the intensity of the individual fluorescence bursts, but rather
      increases the average time spent in the on state. Variations in the quantum
      yields of the different probes correlate well with the degree of conjugation
      between anthracene and the phenylacetylenyl bridge.

PMID- 20131768
TI  - Dynamic copper(I) imaging in mammalian cells with a genetically encoded
      fluorescent copper(I) sensor.
AB  - Copper, a key cofactor for many life processes, is toxic at elevated levels, and
      its availability is strictly controlled inside cells. Therefore, it is a
      challenge to visualize copper availability in the tight copper-binding
      environment of the cell. We report a genetically encoded fluorescent copper(I)
      sensor based on the copper(I)-binding-induced conformational change of a copper
      responsive transcriptional regulator, Amt1. The resulting reporter, Amt1-FRET, is
      ratiometric, highly sensitive (K(d) = 2.5 x 10(-18) M), and selective toward
      copper(I). Its measured high affinity to copper(I) confirms the extremely low
      copper availability in yeast since Amt1 senses the upper limit of cellular copper
      levels in yeast and activates copper detoxification genes. Amt1-FRET operates in
      the dynamic range of the cellular copper buffer in mammalian cells and can report
      dynamic fluctuations of the cellular copper availability within minutes of
      perturbation. Thus, Amt1-FRET visualizes the tightly controlled copper
      availability in mammalian cells.

PMID- 20131769
TI  - Determination of individual diffusion coefficients in evolving binary mixtures by
      taylor dispersion analysis: application to the monitoring of polymer reaction.
AB  - This study demonstrates that it is possible to get valuable information on the
      individual populations of a binary mixture from the signal obtained by Taylor
      dispersion analysis (TDA). In the case of mixtures composed of two populations of
      different sizes (such as a monomer/polymer mixture), the information available
      from TDA is not restricted to an average diffusion coefficient or an average
      hydrodynamic radius calculated on the entire binary mixture. In this work, TDA
      was used to monitor a polymerization reaction. In this scope, it has been
      possible to determine the degree of conversion and the weight average
      hydrodynamic radius of the polymer at different reaction times. Three different
      methods are proposed for the data processing of taylorgrams derived from
      polymerization mixtures or, more generally, for taylorgrams of binary mixtures.
      These three methods, either based on deconvolution or on integration of the
      signal, were found to give similar results. TDA results obtained for a model
      binary mixture of acrylamide and standard polyacrylamide were consistent with DLS
      experiments provided that the differences in the type of average hydrodynamic
      radius values between the two methods are taken into account. An example of
      application to the monitoring of acrylamide radical polymerization is shown.

PMID- 20131770
TI  - DNA duplex stability: the role of preorganized electrostatics.
AB  - The insertion of a DNA base moiety at the end of a DNA duplex to form a Watson
      Crick or wobble pair during DNA annealing or replication is a step of fundamental
      biological importance. Therefore, we investigated the energetics of a formation
      of the terminal G x C, G x T, and G x A base pairs in DNA containing a 5'
      dangling G adjacent to the base insertion point using differential scanning
      calorimetry and computer simulations. The energies calculated along classical
      molecular dynamics trajectories in aqueous solution were analyzed in the
      framework of linear-response approximation (LRA) to obtain relative free energies
      for the base insertion and their electrostatic, van der Waals, and
      preorganization components. Using the generic set of LRA parameters, the
      calculated free energies disfavored the mispair formation by 2.5 (G x C --> G x
      T) and 1.7 (G x C --> G x A) kcal/mol, in reasonable agreement with the
      experimental free energy differences of 1.8 and 1.4 kcal/mol, respectively. The
      calculated preorganization components of these free energies of 0.6 (G x C --> G
      x T) and -0.1 (G x C --> G x A) kcal/mol show that electrostatic preorganization,
      which is an important source of DNA replication fidelity, plays a lesser role in
      the mispair destabilization in the absence of DNA polymerase.

PMID- 20131771
TI  - Computational insights into the interactions between DNA and siRNA with "rigid"
      and "flexible" triazine dendrimers.
AB  - In this study, simulation challenges intuitive models of "flexible" and "rigid"
      generation two triazine dendrimers as it pertains to solution conformation and
      conformation on binding DNA or siRNA sequences. These results derive from
      structural and energetic analyses of the binding events. Simulations of the rigid
      structure reinforce the role of the constrained piperazine linker in positioning
      the peripheral groups at significant distance from each other and the core of the
      dendrimer. In contrast, the flexible dendrimer, characterized by
      triethyleneglycol-like linkers, collapses in solution. On binding DNA and siRNA,
      these conformations are largely retained. The rigid dendrimer undergoes
      reorganization of peripheral groups to generate a large number of contacts to the
      nucleic acid. In contrast, the flexible dendrimer, originally conceived to create
      multivalent interactions with nucleic acids, generates only a few contacts and
      collapses further. This paper provides unique insight in the role played by
      molecular flexibility in the binding phenomenon.

PMID- 20131772
TI  - A nonaqueous lyotropic liquid crystal fabricated by a polyoxyethylene amphiphile
      in protic ionic liquid.
AB  - The aggregation behaviors of oleyl polyoxyethylene (10) ether, Brij 97, in room
      temperature ionic liquids, ethylammonium nitrate (EAN), pyrrolidinium nitrate
      ([Pyrr][NO(3)]), ethylammonium butyrate (EAB), 1-butyl-3-methylimidazolium
      hexafluorophosphate ([Bmim][PF(6)]), and 1-butyl-3-methylimidazolium
      tetrafluoroborate ([Bmim][BF(4)]), have been investigated. Only in the Brij
      97/EAN binary system is the hexagonal liquid crystalline phase formed, and its
      ordering is found to decrease with increasing temperature. The lattice spacing
      values measured from the small-angle X-ray scattering (SAXS) shrink with
      reduction of ionic liquid content at room temperature. The general rules for
      aggregate formation in these ionic liquids are discussed and compared with that
      in water. A degraded ability to produce the ordered self-assembly of Brij 97 from
      H(2)O to EAN to [Bmim][PF(6)], [Bmim][BF(4)], [Pyrr][NO(3)], and EAB is found and
      analyzed based on the molecular packing and Gordon parameters and also hydrogen
      bonding or solvophobic interactions. Steady-shear rheological measurements
      combined with the frequency sweep data indicate the highly viscoelastic nature of
      this liquid crystalline phase.

PMID- 20131773
TI  - Dynamics of thinning of foam films stabilized by n-dodecyl-beta-maltoside.
AB  - We studied the process of thinning of thin liquid films stabilized with the
      nonionic surfactant n-dodecyl-beta-maltoside (beta-C(12)G(2)) with primary
      interest in interfacial diffusion processes during the thinning process dependent
      on surfactant concentration. The surfactant concentration in the film forming
      solutions was varied from 0.01 to 1.0 mM through the critical micellar
      concentration of 0.16 mM at constant electrolyte (NaCl) concentration, nominally
      0.2 M. This assures the formation of Newton black films at the end of the
      thinning process. The velocity of thinning was analyzed combining previously
      developed theoretical approaches. From the model, which accounts for diffusion
      processes in the bulk of the film and in the interfaces, an analytical function
      was derived and fitted numerically to the experimental data. Quantitative
      information about the mobility of the surfactant molecules at the film surfaces
      could be obtained. We find that above a surfactant concentration of 0.12 mM (beta
      C(12)G(2)) the film surfaces behave as immobile and nondeformable which
      decelerates the thinning process. This follows the predictions for Reynolds flow
      of liquid between two nondeformable disks. Moreover, we could apply the theory on
      free area dependent diffusion coefficients on our results and show that it is in
      reasonable ranges applicable on the used surfactant system.

PMID- 20131774
TI  - Enantioselective carbonyl allylation, crotylation, and tert-prenylation of furan
      methanols and furfurals via iridium-catalyzed transfer hydrogenation.
AB  - 5-Substituted-2-furan methanols 1a-c are subject to enantioselective carbonyl
      allylation, crotylation and tert-prenylation upon exposure to allyl acetate,
      alpha-methyl allyl acetate, or 1,1-dimethylallene in the presence of an ortho
      cyclometalated iridium catalyst modified by (R)-Cl,MeO-BIPHEP, (R)-C3-TUNEPHOS,
      and (R)-C3-SEGPHOS, respectively. In the presence of 2-propanol, but under
      otherwise identical conditions, the corresponding substituted furfurals 2a-c are
      converted to identical products of allylation, crotylation, and tert-prenylation.
      Optically enriched products of carbonyl allylation, crotylation, and reverse
      prenylation 3b, 4b, and 5b were subjected to Achmatowicz rearrangement to furnish
      the corresponding gamma-hydroxy-beta-pyrones 6a-c, respectively, with negligible
      erosion of enantiomeric excess.

PMID- 20131775
TI  - Iron(III)-catalyzed four-component coupling reaction of 1,3-dicarbonyl compounds,
      amines, aldehydes, and nitroalkanes: a simple and direct synthesis of
      functionalized pyrroles.
AB  - A simple, convenient, and multicomponent coupling strategy for the synthesis of
      highly functionalized pyrroles catalyzed by iron(III) salts has been developed.
      This strategy demonstrated four-component coupling reactions of 1,3-dicarbonyl
      compounds, amines, aromatic aldehydes, and nitroalkanes without an inert
      atmosphere. This methodology provides an alternative approach for easy access of
      highly substituted pyrroles in moderate to very good yields using four simple and
      readily available building blocks via one-pot tandem reaction. Notably, this
      method is very cheap, straightforward, and environmentally friendly compared to
      the existing methods.

PMID- 20131776
TI  - Optimizing the polarization matrix for ex situ dynamic nuclear polarization.
AB  - Although recent advances in dynamic nuclear polarization techniques have boosted
      the otherwise low sensitivity of NMR spectroscopy, the efficiency of the
      hyperpolarization process depends on the composition of the polarization matrix,
      in particular on the contact between the radical and the target molecule and the
      capability of the matrix to transfer polarization through spin diffusion. A
      concept for optimal matrix design is presented, applied to obtain two-dimensional
      heterocorrelated spectra of small drug-like molecules in 1-2 min after 90 min of
      hyperpolarization.

PMID- 20131777
TI  - Copper-catalyzed direct alkynylation of electron-deficient polyfluoroarenes with
      terminal alkynes using O2 as an oxidant.
AB  - A copper-catalyzed direct alkynylation of electron-deficient polyfluoroarenes
      with a wide range of terminal alkynes is realized for the first time. The
      reaction proceeds under mild conditions with O(2) as an oxidant.

PMID- 20131778
TI  - Selective pairwise encapsulation using directional interactions.
AB  - Trimethylamine N-oxide and trimethylphosphine oxide guests are pairwise
      encapsulated in a dimeric capsule self-assembled from a tetraurea aryl extended
      calix[4]pyrrole. The capsule possesses polar functional groups in its interior
      capable of controlling the orientation of the included guests. A modest
      selectivity is observed during the encapsulation process that is beyond the
      controls of size or shape exclusion.

PMID- 20131779
TI  - Polyacrylamide gel photopatterning enables automated protein immunoblotting in a
      two-dimensional microdevice.
AB  - We demonstrate a two-dimensional microfluidic architecture that integrates
      polyacrylamide gel electrophoresis (PAGE) with immunoblotting in a fully
      automated format. This assay is designed to overcome performance limitations of
      conventional slab-gel immunoblotting, including multiple manual interventions,
      low-throughput transfer and blotting, and substantial consumption of reagents and
      sample. To unify PAGE with blotting in one device, this microfluidic approach
      makes use of high-resolution regional photopatterning of multiple polyacrylamide
      gel elements, and automated electrophoretic transport. A complete native
      immunoblot of free prostate specific antigen from human seminal fluid is
      demonstrated in less than 5 min. Further, the characterization of post-PAGE
      electrophoretic transfer showed high efficiency and minimal sample dispersion.

PMID- 20131780
TI  - Multiplexed DNA-modified electrodes.
AB  - We report the use of silicon chips with 16 DNA-modified electrodes (DME chips)
      utilizing DNA-mediated charge transport for multiplexed detection of DNA and DNA
      binding protein targets. Four DNA sequences were simultaneously distinguished on
      a single DME chip with 4-fold redundancy, including one incorporating a single
      base mismatch. These chips also enabled investigation of the sequence-specific
      activity of the restriction enzyme Alu1. DME chips supported dense DNA monolayer
      formation with high reproducibility, as confirmed by statistical comparison to
      commercially available rod electrodes. The working electrode areas on the chips
      were reduced to 10 microm in diameter, revealing microelectrode behavior that is
      beneficial for high sensitivity and rapid kinetic analysis. These results
      illustrate how DME chips facilitate sensitive and selective detection of DNA and
      DNA-binding protein targets in a robust and internally standardized multiplexed
      format.

PMID- 20131781
TI  - Aromatic-aromatic interactions induce the self-assembly of pentapeptidic
      derivatives in water to form nanofibers and supramolecular hydrogels.
AB  - In this paper we report the conjugation of an aromatic moiety (pyrene (P),
      fluorene (F), or naphthalene (N)) to pentapeptides GAGAS (1), GVPVP (2), VPGVG
      (3), VTEEI (4), VYGGG (5), and YGFGG (6) to afford peptidic derivatives for
      exploring pentapeptide-based hydrogels as potential biomaterials. Most of these
      compounds (1F, 1P, 2F, 2P, 4F, 4P, 4N, 5F, 5N, 6F, 6P, and 6N) behave as
      molecular hydrogelators and can form hydrogels at minimum concentrations of
      gelation from 0.5 to 2.8 wt %. The fluorescence spectra of the hydrogels exhibit
      a significant red shift, indicating the interactions between the aromatic
      moieties in those hydrogels. The circular dichroism spectra indicate that the
      self-assembly of the hydrogelators affords helical or beta-sheet-like structures.
      Transmission and scanning electron microscopic examination reveals the nanofiber
      networks of these hydrogelators. In addition, rheological measurements show fair
      to excellent viscoelastic properties of these hydrogels. The balance of
      intermolecular aromatic-aromatic interactions and hydrogen bonds of these
      hydrogelators leads to their self-assembly in water and the formation of
      nanofibers as the matrixes of hydrogels. A total of 6 of these 18 pentapeptide
      derivatives--1N, 2N, 3F, 3P, 3N, and 5P--fail to form hydrogels under the
      conditions tested, likely due to unbalanced intermolecular interactions. This
      work suggests that aromatic-aromatic interactions are useful and favorable forces
      for creating molecular nanofibers and supramolecular hydrogels.

PMID- 20131782
TI  - Life cycle assessment and grid electricity: what do we know and what can we know?
AB  - The generation and distribution of electricity comprises nearly 40% of U.S.
      CO(2), emissions, as well as large shares of SO(2), NO(x), small particulates,
      and other toxins. Thus, correctly accounting for these electricity-related
      environmental releases is of great importance in life cycle assessment of
      products and processes. Unfortunately, there is no agreed-upon protocol for
      accounting for the environmental emissions associated with electricity, as well
      as significant uncertainty in the estimates. Here, we explore the limits of
      current knowledge about grid electricity in LCA and carbon footprinting for the
      U.S. electrical grid, and show that differences in standards, protocols, and
      reporting organizations can lead to important differences in estimates of CO(2)
      SO(2), and NO(x) emissions factors. We find a considerable divergence in
      published values for grid emissions factor in the U.S. We discuss the
      implications of this divergence and list recommendations for a standardized
      approach to accounting for air pollution emissions in life cycle assessment and
      policy analyses in a world with incomplete and uncertain information.

PMID- 20131783
TI  - Accounting for natural resources and environmental sustainability: linking
      ecosystem services to human well-being.
AB  - One of society's greatest challenges is to sustain natural resources while
      promoting economic growth and quality of life. In the face of this challenge,
      society must measure the effectiveness of programs established to safeguard the
      environment. The impetus for demonstrating positive results from government
      sponsored research and regulation in the United States comes from Congress
      (General Accountability Office; GAO) and the Executive Branch (Office of
      Management and Budget; OMB). The message is: regulatory and research programs
      must demonstrate outcomes that justify their costs. Although the concept is
      simple, it is a complex problem to demonstrate that environmental research,
      policies, and regulations cause measurable changes in environmental quality. Even
      where changes in environmental quality can be tracked reliably, the connections
      between government actions and environmental outcomes seldom are direct or
      straightforward. In this article, we describe emerging efforts (with emphasis on
      the role of the U.S. Environmental Protection Agency; EPA) to frame and measure
      environmental outcomes in terms of ecosystem services and values-societally and
      ecologically meaningful metrics for gauging how well we manage environmental
      resources. As examples of accounting for outcomes and values, we present a novel,
      low-cost method for determining relative values of multiple ecosystem services,
      and describe emerging research on indicators of human well-being.

PMID- 20131784
TI  - Stream temperature response to three riparian vegetation scenarios by use of a
      distributed temperature validated model.
AB  - Elevated in-stream temperature has led to a surge in the occurrence of parasitic
      intrusion proliferative kidney disease and has resulted in fish kills throughout
      Switzerland's waterways. Data from distributed temperature sensing (DTS) in
      stream measurements for three cloud-free days in August 2007 over a 1260 m
      stretch of the Boiron de Merges River in southwest Switzerland were used to
      calibrate and validate a physically based one-dimensional stream temperature
      model. Stream temperature response to three distinct riparian conditions were
      then modeled: open, in-stream reeds, and forest cover. Simulation predicted a
      mean peak stream temperature increase of 0.7  degrees C if current vegetation was
      removed, an increase of 0.1  degrees C if dense reeds covered the entire stream
      reach, and a decrease of 1.2  degrees C if a mature riparian forest covered the
      entire reach. Understanding that full vegetation canopy cover is the optimal
      riparian management option for limiting stream temperature, in-stream reeds,
      which require no riparian set-aside and grow very quickly, appear to provide
      substantial thermal control, potentially useful for land-use management.

PMID- 20131785
TI  - Local to continental influences on nutrient and contaminant sources to river
      birds.
AB  - Stable isotope and contaminant analyses revealed differences in nutrient sources
      and contaminant pathways in two species of dipper, Cinclus mexicanus and Cinclus
      cinclus in western Canada and western Britain. We collected dipper prey and eggs
      from relatively pristine British Columbian rivers contrasting in the presence of
      salmon-derived nutrients, and rural Welsh rivers with varying food-web complexity
      associated with stream acidity. Enriched delta(13)C and to a lesser extent
      delta(15)N in American dipper eggs and prey confirmed that streams with migrating
      Pacific salmon were enriched with marine-derived nutrients, but overall
      contaminant concentrations did not differ strongly in dipper eggs between rivers
      with and without salmon. However dipper contaminant profiles, particularly PBDEs,
      mercury and SigmaDDTs, were related to delta(13)C, reflecting the marine
      influence and greater fish consumption at salmon sites. Irrespective of catchment
      influences and despite feeding at a higher trophic level, American dipper eggs (n
      = 17) contained lower levels of organohalogens than Eurasian dippers (n = 37),
      but with similar PCB (153 and 138) and PBDE (47 and 99) congeners dominanating.
      Eurasian dipper eggs from circumneutral streams contained more dieldrin, SigmaDDT
      and Sigmahexachlorocyclohexanes while Sigmachlordanes, mirex, SigmaPBDEs and
      SigmaPCBs predominated at acid sites. Our data reveal how dippers indicate
      contaminant levels and sources under contrasting conditions at scales ranging
      from local to intercontinental, but local environmental conditions apparently
      alter feeding ecology and exposure pathways even in these closely related
      species.

PMID- 20131786
TI  - Easy access to a family of polymer catalysts from modular star polymers.
AB  - We report a versatile and scalable synthesis of a water-dispersible modular star
      polymer platform with an enzyme-inspired hydrophobic interior. The cores of the
      stars can be functionalized at will, independently from the modification of the
      polymer structure. We explored the use of this material for the creation of a
      local hydrophobic solvent environment in water and for site isolation of
      incompatible catalytic entities.

PMID- 20131787
TI  - Analysis, distribution, and dietary exposure of glyoxal and methylglyoxal in
      cookies and their relationship with other heat-induced contaminants.
AB  - Thermal processing of food leads to the formation of dicarbonyls such as glyoxal
      (GO) and methylglyoxal (MGO), which are potentially harmful because they are
      precursors of advanced glycation end products (AGEs). GO and MGO formation was
      examined during the baking process of cookies as cookies are a widely distributed
      food commodity in Western diets. GO and MGO were chromatographically analyzed
      after employment of an improved method of derivatization with
      orthophenylenediamine to produce stable quinoxaline derivatives. Sample
      extraction, cleanup, and chromatographic conditions were evaluated to provide an
      in-house validated procedure for GO and MGO analysis in cookies. Quantification
      limits were set at 1.5 and 2 mg/kg for GO and MGO, respectively, with an average
      recovery of 103% and a calculated precision lower than 7%. Studies were carried
      out both on laboratory-scale cookies under controlled conditions and on
      commercial samples as well. GO and MGO values in commercial cookies ranged from
      4.8 to 26.0 mg/kg and from 3.7 to 81.4 mg/kg, respectively. Commercial cookies
      made from ammonium bicarbonate and fructose showed the highest levels of MGO.
      Dicarbonyls were rapidly formed on the upper side of the cookie regardless of the
      shape or thickness of the samples, confirming there was a surface effect. Under
      controlled baking conditions, the formations of GO and MGO were linearly
      correlated with baking time. MGO formation was related with acrylamide, a heat
      processing contaminant, in commercial cookies, but this relationship was not
      observed for 5-hydroxymethylfurfural. Dietary exposure of the Spanish population
      to GO and MGO from cookies was estimated to be 213 and 216 microg/person/day,
      respectively.

PMID- 20131788
TI  - Synergetic effect and structure-activity relationship of 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors from Crataegus pinnatifida Bge.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors from
      hawthorn fruit ( Crataegus pinnatifida Bge.) were isolated and evaluated for
      their antihyperlipidemic effect induced by high-fat diet in mice. After being
      further purified with silica and polyamide column chromatography from the
      fractions (fractions A, F, H, and G) with a high inhibitory rate (IR) to HMGR, 24
      chromatographic fractions were obtained, including 8 active fractions with a high
      IR to HMGR. However, the total inhibitory activity of 24 fractions was decreased
      by about 70%. From eight active fractions, four compounds were obtained by
      recrystallization and identified as quercetin (a), hyperoside (b), rutin (c), and
      chlorogenic acid (d), the contents of which in hawthorn EtOH extract were 0.16,
      0.32, 1.45, and 0.95%, respectively. The IR values of compounds a-d to HMGR were
      6.28, 9.64, 23.53, and 10.56% at the corresponding concentrations of 0.16, 0.32,
      1.45, and 0.95 mg/mL, respectively. It was discovered that the IR of a mixture
      (2.85 mg/mL) matching the original percentage of compounds a-d in hawthorn EtOH
      extract was up to 79.5%, much higher than that of the single compound and the
      total IR of these four compounds (50.01%). The in vivo results also revealed that
      the mixture had a more significant lipid-lowering efficacy than the monomers.
      Structure-activity relationship revealed the inhibitory activity and lowering
      lipid ability of compounds a-c decreased with increasing glycoside numbers. It
      was concluded that there were synergetic effects on inhibiting HMGR and lowering
      lipid among compounds a-d, and the weak hydrophilic ability benefits the
      inhibition to HMGR and lowering-lipid efficacy.

PMID- 20131789
TI  - Simultaneous production of trehalose, bioethanol, and high-protein product from
      rice by an enzymatic process.
AB  - Rice is a starch-rich raw material that can be used for trehalose production. It
      can be hydrolyzed with alpha-amylase, beta-amylase, and pullulanase to produce
      high-maltose content of rice saccharified solution for bioconversion of maltose
      into trehalose by trehalose synthase (TSase). For this purpose, an efficient
      enzymatic procedure has been successfully developed to simultaneously produce
      value-added trehalose, bioethanol, and high-protein product from rice as
      substrate. The highest maltose yield produced from the liquefied rice starch
      hydrolysate was 82.4 +/- 2.8% at 50 degrees C and pH 5.0 for 21-22 h. The
      trehalose conversion rate can reach at least 50% at 50 degrees C and pH 5.0 for
      20-24 h by a novel thermostable recombinant Picrophilus torridus trehalose
      synthase (PTTS). All residual sugar, except trehalose, can be fully hydrolyzed by
      glucoamylase into glucose for further bioethanol production. The insoluble
      byproduct containing high yields of protein (75.99%) and dietary fiber (14.01%)
      can be processed as breakfast cereal product, health food, animal forage, etc.
      The conversion yield of bioethanol was about 98% after 64 h of fermentation time
      by Saccharomyces cerevisiae without any artificial culture solution addition.
      Ethanol can easily be separated from trehalose by distillation with a high
      recovery yield and purity of crystalline trehalose of 92.5 +/- 8.7% and 92.3%,
      respectively.

PMID- 20131790
TI  - Insight into the unique oxidation chemistry of elemental mercury by chlorine
      containing species: experiment and simulation.
AB  - This work investigated the oxidation chemistry of elemental mercury (Hg(0)) by
      chlorine-containing species produced indirectly through the gas-to-solid phase
      reaction between NO(x) gases and NaClO(2) powder (NaClO(2)(s)), where both
      experiment and simulation results were compared to clarify which species are
      responsible for the oxidation of Hg(0). At first, we introduced 30 ppm of NO(2)
      into the pack-bed reactor containing NaClO(2)(s) to produce OClO species and then
      injected NO and Hg(0) (260 microg/Nm(3)) to Mixer, where the concentration of NO
      was varied up to 180 ppm and the reaction temperature was set to 130 degrees C.
      We observed for the first time that the degree of Hg(0) oxidation is completely
      controlled by the introduced concentration of NO: for example, the oxidation
      efficiency of Hg(0) is drastically increased to become 100% at near 7 ppm NO, but
      further increasing NO concentration results in the oxidation efficiency of Hg(0)
      being gradually decreased. The simulation results indicated that such a
      propensity of Hg(0) oxidation efficiency to NO concentration can be attributed to
      the NO concentration-dependent Cl, ClO, and Cl(2) formation which plays a
      critical role in the oxidation of Hg(0).

PMID- 20131791
TI  - Efficient removal of organic pollutants with magnetic Nanoscaled BiFeO(3) as a
      reusable heterogeneous fenton-like catalyst.
AB  - BiFeO(3) magnetic nanoparticles (BFO MNPs) were prepared with a sol-gel method
      and characterized as a catalyst. It was found that BFO MNPs effectively catalyzed
      the decomposition of H(2)O(2) into *OH radicals, being confirmed with electron
      spin resonance spin-trapping technique and other radical probing techniques. The
      strong H(2)O(2)-activating ability of BFO MNPs showed promising applications in
      the oxidative degradation of organic pollutants. When BFO MNPs were used as a
      heterogeneous Fenton-like catalyst to degrade Rhodamine B, the apparent rate
      constant for the RhB degradation at 25 degrees C at pH 5.0 in the BFO MNPs
      H(2)O(2) system was evaluated to be 2.89 x 10(-2) min(-1), being about 20 folds
      of that obtained with Fe(3)O(4) MNPs as the catalyst under similar conditions.
      Moreover, BFO MNPs were demonstrated to have excellent stability and reusability.
      The catalytic mechanism of BFO MNPs was also investigated with Monte Carlo
      simulations and density functional theory calculations.

PMID- 20131792
TI  - Adhesion of Shewanella oneidensis MR-1 to iron (Oxy)(Hydr)oxides: microcolony
      formation and isotherm.
AB  - The adhesion of dissimilatory metal reducing bacteria (DMRB) to iron
      (oxy)(hydr)oxides may play an important role in their respiration on ferric iron
      containing minerals, but few quantitative surface cell density measurements have
      been made thus far. We used confocal microscopy to examine the adhesion of a
      common DMRB species, Shewanella oneidensis MR-1, onto iron (oxy)(hydr)oxide
      particulate-coated glass slides across a broad range of bulk (i.e., solution
      phase) cell densities from 10(5) cells/mL to 2 x 10(9) cells/mL. At bulk cell
      densities less than 1 x 10(7) cells/mL, cells adhered to the slide surface formed
      an evenly distributed, homogeneous monolayer, while at the bulk cell densities
      higher than 2 x 10(8) cells/mL the adhered cells formed distinct microcolonies.
      As a result of this complex adhesion behavior, simple Langmuir or Freundlich
      adsorption isotherms do not capture the relationship between the surface cell
      density and the bulk cell density over the entire range of bulk cell densities.
      Thus a new, two-step isotherm was developed that incorporated both isolated
      attached cells at low cell densities as well as microcolonies at higher cell
      densities.

PMID- 20131793
TI  - Relationship between fresh-packaged spinach leaves exposed to continuous light or
      dark and bioactive contents: effects of cultivar, leaf size, and storage
      duration.
AB  - Current retail marketing conditions allow produce to receive artificial light 24
      h per day during its displayed shelf life. Essential human-health vitamins
      [ascorbic acid (vit C), folate (vit B(9)), phylloquinone (vit K(1)), alpha
      tocopherol (vit E), and the carotenoids lutein, violaxanthin, zeaxanthin, and
      beta-carotene (provit A)] also are essential for photosynthesis and are
      biosynthesized in plants by light conditions even under chilling temperatures.
      Spinach leaves, notably abundant in the aforementioned human-health compounds,
      were harvested from flat-leaf 'Lazio' and crinkle-leafed 'Samish' cultivars at
      peak whole-plant maturity as baby (top- and midcanopy) and larger (lower-canopy)
      leaves. Leaves were placed as a single layer in commercial, clear-polymer retail
      boxes and stored at 4 degrees C for up to 9 days under continuous light (26.9
      micromol.m(2 ).s) or dark. Top-canopy, baby-leaf spinach generally had higher
      concentrations of all bioactive compounds, on a dry weight basis, with the
      exception of carotenoids, than bottom-canopy leaves. All leaves stored under
      continuous light generally had higher levels of all bioactive compounds, except
      beta-carotene and violaxanthin, and were more prone to wilting, especially the
      flat-leafed cultivar. All leaves stored under continuous darkness had declining
      or unchanged levels of the aforementioned bioactive compounds. Findings from this
      study revealed that spinach leaves exposed to simulated retail continuous light
      at 4 degrees C, in clear plastic containers, were overall more nutritionally
      dense (enriched) than leaves exposed to continuous darkness.

PMID- 20131794
TI  - Kinetic modeling of the thermal inactivation of bacteriocin-like inhibitory
      substance p34.
AB  - Optimization of thermal processes relies on adequate degradation kinetic models
      to warrant food safety and quality. The knowledge on thermal inactivation
      kinetics of antimicrobial peptides is necessary to allow for their adequate use
      as natural biopreservatives in the food industry. In this work, thermal
      inactivation of the previously characterized bacteriocin-like inhibitory
      substance (BLIS) P34 was kinetically investigated within the temperature range of
      90-120 degrees C. Listeria monocytogenes ATCC 7644 was used as the indicator
      microorganism for antimicrobial activity. Applicability of various inactivation
      models available in the literature was critically evaluated. The first-order
      model provided the best description of the kinetics of inactivation over the
      selected temperatures, with k values between 0.059 and 0.010 min(-1). D and k
      values decreased and increased, respectively, with increasing temperature,
      indicating a faster inactivation at higher temperatures. Results suggest that
      BLIS P34 is thermostable, with a z value of 37.74 degrees C and E(a) of 72 kJ
      mol(-1).

PMID- 20131796
TI  - Application of photo-fenton as a tertiary treatment of emerging contaminants in
      municipal wastewater.
AB  - This work focuses on the treatment of real effluents from a municipal wastewater
      treatment plant (RE) with solar photo-Fenton (5 mg and 20 mg L(-1) Fe, pH
      approximately 3 and 50 mg L(-1) initial H(2)O(2) concentration) at pilot plant
      scale. In some experiments RE was spiked with 15 different (acetaminophen,
      antipyrine, atrazine, caffeine, carbamazepine, diclofenac, flumequine,
      hydroxybiphenyl, ibuprofen, isoproturon, ketorolac, ofloxacin, progesterone,
      sulfamethoxazole, and triclosan) emerging contaminants (ECs) at 100 and 5 microg
      L(-1) each which were added directly into RE prior to treatment. All experiments
      showed successful degradation of ECs in real effluents from different municipal
      wastewater treatment plants at low iron concentration (5 mg L(-1)). Although the
      most degradation took place during the Fenton process, photo-Fenton was necessary
      to degrade all ECs below their limit of detection (LOD). In the case of the RE
      containing 52 ECs (determined by HPLC-QTRAP-MS), four of them could not be
      degraded to their LOD and were still present, although at extremely low
      concentrations (nicotine 47 ng L(-1), cotinine 11 ng L(-1), chlorfenvinphos 99 ng
      L(-1), and caffeine 8 ng L(-1)). ECs were easily degraded by (*)OH without
      substantial competition with the organic content of the RE.

PMID- 20131795
TI  - Intramolecular anodic olefin coupling reactions and the synthesis of cyclic
      amines.
AB  - Anodic olefin coupling reactions using a tosylamine trapping group have been
      studied. The cyclizations are favored by the use of a less-polar radical cation
      and more basic reaction conditions. The most significant factor for obtaining
      good yields of cyclic product is the use of the more basic reaction conditions.
      However, a number of factors including the nature of both the solvent and the
      electrolyte used can influence the yield of the cyclizations. The cyclizations
      allow for the rapid synthesis of both substituted proline and pipecolic acid type
      derivatives.

PMID- 20131797
TI  - Determination of digestibility, tissue deposition, and metabolism of the omega-3
      fatty acid content of krill protein concentrate in growing rats.
AB  - Krill protein concentrate (KPC) consists of high-quality protein (77.7% dry
      basis) and lipids (8.1% dry basis) that are rich (27% of total fatty acids) in
      omega-3 polyunsaturated fatty acids (omega-3 PUFAs). The objective of the study
      was to determine digestibility, tissue deposition, metabolism, and tissue
      oxidative stability of the omega-3 PUFAs provided by KPC. Young female Sprague
      Dawley rats (n = 10/group) were fed ad libitum isocaloric diets for 4 weeks with
      either 10% freeze-dried KPC or 10% casein. The casein diet contained 5.3% added
      corn oil (CO), whereas the KPC contained 5.3% total lipids from 0.9% krill oil
      (KO) provided by KPC and 4.4% added corn oil (KO + CO). Fatty acid compositions
      of various tissues were analyzed by gas chromatography. Lipid peroxidation was
      determined by thiobarbituric acid reactive substances (TBARS). Total antioxidant
      capacity and urinary eicosanoid metabolites were determined by enzyme
      immunoassay. The omega-3 PUFAs provided in KO from KPC increased (P = 0.003)
      docosahexaenoic acid (DHA) concentration in the brain. DHA and eicosapentaenoic
      acid (EPA) content in fat pads and liver were increased (P < 0.01), whereas the
      omega-6 PUFA, arachidonic acid (AA), was decreased (P < 0.01) in rats fed the KPC
      diet containing the KO + CO mixture compared to rats fed the casein diet
      containing pure CO. Feeding the KPC diet decreased pro-inflammatory 2-series
      prostaglandin and thromboxane metabolites. There was no significant difference in
      TBARS or total antioxidant capacity in the tissues of rats fed the different
      diets. On the basis of the study results, the low amount of omega-3 PUFAs
      provided by the KO content of KPC provides beneficial effects of increasing
      tissue EPA and DHA deposition and reduced AA-derived 2-series eicosanoid
      metabolites without increasing lipid peroxidation. Therefore, consumption of KPC
      has the potential to provide a healthy and sustainable source of omega-3 PUFAs.

PMID- 20131798
TI  - Development of hapten-linked microimmunoassays on polycarbonate discs.
AB  - An amino-modified polycarbonate surface of compact discs is used to link haptens
      covalently and directly as an alternative to the classic protein-hapten conjugate
      adsorption coating strategy employed in immunoassays. The modified surface
      maintains its physical and optical properties, and a standard disk drive can then
      read the assay results. Advantages are evaluated, such as the use of a broader
      spectrum of coupling media including organic solvents that are inappropriate for
      proteins but necessary for some water-insoluble haptens and the bypassing of the
      synthesis and purification for protein conjugates. As proof of concept,
      competitive microimmunoassays were developed for chlorpyrifos, atrazine, and 2
      (2,4,5-trichlorophenoxy)propionic acid (2,4,5-TP), in microarray format,
      obtaining detection limits of 37.2, 8.1, and 76 ng/L, respectively. The
      sensitivity was 1 order of magnitude better than that obtained for all the
      studied systems using hapten-protein conjugates adsorbed on polystyrene enzyme
      linked immunosorbent assay (ELISA) plates and polycarbonate surfaces. Further,
      the influence of hapten structure and presentation on molecular recognition
      pattern is discussed. To our knowledge, this is the first time that microarray
      and compact disc technologies converge with this particular hapten immobilization
      mode. The great potential of the approach is demonstrated through the high
      throughput capability of the disc in a range of analytical applications, as well
      as the inherent advantages of compact disc reading technology.

PMID- 20131799
TI  - Evaluation of full-resolution J-resolved 1H NMR projections of biofluids for
      metabonomics information retrieval and biomarker identification.
AB  - Spectroscopic profiling of biological samples is an integral part of
      metabolically driven top-down systems biology and can be used for identifying
      biomarkers of toxicity and disease. However, optimal biomarker information
      recovery and resonance assignment still pose significant challenges in NMR-based
      complex mixture analysis. The reduced signal overlap as achieved when projecting
      two-dimensional (2D) J-resolved (JRES) NMR spectra can be exploited to mitigate
      this problem and, here, full-resolution (1)H JRES projections have been evaluated
      as a tool for metabolic screening and biomarker identification. We show that the
      recoverable information content in JRES projections is intrinsically different
      from that in the conventional one-dimensional (1D) and Carr-Purcell-Meiboom-Gill
      (CPMG) spectra, because of the combined result of reduction of the over
      representation of highly split multiplet peaks and relaxation editing. Principal
      component and correlation analyses of full-resolution JRES spectral data
      demonstrated that peak alignment is necessary. The application of statistical
      total correlation spectroscopy (STOCSY) to JRES projections improved the
      identification of previously overlapped small molecule resonances in JRES (1)H
      NMR spectra, compared to conventional 1D and CPMG spectra. These approaches are
      demonstrated using a galactosamine-induced hepatotoxicity study in rats and show
      that JRES projections have a useful and complementary role to standard one
      dimensional experiments in complex mixture analysis for improved biomarker
      identification.

PMID- 20131800
TI  - Proteins modified by the lipid peroxidation aldehyde 9,12-dioxo-10(E)-dodecenoic
      acid in MCF7 breast cancer cells.
AB  - The hydroperoxide of linoleic acid (13-HPODE) degrades to 9,12-dioxo-10(E)
      dodecenoic acid (DODE), which readily modifies proteins. This study identified
      the major proteins in MCF7 cells modified by DODE. To reduce false positives,
      three methods were used to identify DODE-modified proteins. First, cells were
      treated with a synthetically biotinylated 13-HPODE (13-HPODE-biotin). Modified
      proteins were enriched by neutravidin affinity and identified by two-dimensional
      liquid chromatography--tandem mass spectrometry (2D LC-MS/MS). Second, cells were
      treated with native 13-HPODE. Protein carbonyls were biotinylated with an
      aldehyde reactive probe, and modified proteins were enriched by neutravidin
      affinity and identified by 2D LC-MS/MS. Third, using a newly developed DODE
      antibody, DODE-modified proteins were located by 2D sodium dodecyl sulfate-
      polyacrylamide gel electrophoresis and Western blot and identified by in-gel
      digestion and LC-MS/MS. Analysis of the proteins characterized by all three
      methods revealed a significant overlap and identified 32 primary proteins
      modified by DODE in MCF7 cells. These results demonstrated the feasibility for
      the cellular formation of DODE protein-carbonyl adducts that may be future
      indicators of oxidative stress.

PMID- 20131802
TI  - 3-(4-Methylfuran-3-yl)propan-1-ol: a white-spotted Stinkbug ( Eysarcoris
      ventralis ) repellent produced by an endophyte isolated from green foxtail.
AB  - Stinkbug is a major rice plant pest in Asia. The extract of the culture filtrate
      of a fungus isolated from a green foxtail, Setaria viridis (L.) Beauv., was found
      to have a repellent effect on the white-spotted stinkbug, Eysarcoris ventralis
      (Westwood). The active principle was purified and isolated, and identified as 3
      (4-methylfuran-3-yl)propan-1-ol (1) on the basis of spectroscopic data. Four acyl
      derivatives were prepared from 1 and assessed for repellent effect on the
      stinkbug; the acetyl derivative 2 was most effective.

PMID- 20131801
TI  - Structure of epi-isozizaene synthase from Streptomyces coelicolor A3(2), a
      platform for new terpenoid cyclization templates.
AB  - The X-ray crystal structure of recombinant epi-isozizaene synthase (EIZS), a
      sesquiterpene cyclase from Streptomyces coelicolor A3(2), has been determined at
      1.60 A resolution. Specifically, the structure of wild-type EIZS is that of its
      closed conformation in complex with three Mg(2+) ions, inorganic pyrophosphate
      (PP(i)), and the benzyltriethylammonium cation (BTAC). Additionally, the
      structure of D99N EIZS has been determined in an open, ligand-free conformation
      at 1.90 A resolution. Comparison of these two structures provides the first view
      of conformational changes required for substrate binding and catalysis in a
      bacterial terpenoid cyclase. Moreover, the binding interactions of BTAC may mimic
      those of a carbocation intermediate in catalysis. Accordingly, the aromatic rings
      of F95, F96, and F198 appear to be well-oriented to stabilize carbocation
      intermediates in the cyclization cascade through cation-pi interactions.
      Mutagenesis of aromatic residues in the enzyme active site results in the
      production of alternative sesquiterpene product arrays due to altered modes of
      stabilization of carbocation intermediates as well as altered templates for the
      cyclization of farnesyl diphosphate. Accordingly, the 1.64 A resolution crystal
      structure of F198A EIZS in a complex with three Mg(2+) ions, PP(i), and BTAC
      reveals an alternative binding orientation of BTAC; alternative binding
      orientations of a carbocation intermediate could lead to the formation of
      alternative products. Finally, the crystal structure of wild-type EIZS in a
      complex with four Hg(2+) ions has been determined at 1.90 A resolution, showing
      that metal binding triggers a significant conformational change of helix G to cap
      the active site.

PMID- 20131803
TI  - Modulation of multimetal complexation behavior of tetraoxime ligand by covalent
      transformation of olefinic functionalities.
AB  - A new multimetal complexation system that can change its complexation behavior by
      C-C bond formation has been developed. The acyclic tetraoxime ligand H(4)L(1)
      having two terminal allyl groups was synthesized. The olefin metathesis of
      H(4)L(1) selectively produced trans-H(4)L(2) while the reaction of [L(1)Zn(2)Ca]
      exclusively afforded cis-H(4)L(2). The saturated analogue H(4)L(3) was
      synthesized by hydrogenation. The complexation of the ligands H(4)L (L = L(1),
      trans-L(2), cis-L(2), L(3)) with zinc(II) acetate (3 equiv) yielded the
      trinuclear complexes [LZn(3)] with a similar trinuclear core bridged by acetato
      ligands. Whereas the formation process of [L(1)Zn(3)] having an acyclic ligand
      was highly cooperative, the macrocyclic analogues [LZn(3)] (L = trans-L(2), cis
      L(2), L(3)) were formed in a stepwise fashion via the intermediate 2:3 complex
      [(HL)(2)Zn(3)]. The trinuclear complexes [LZn(3)] (L = L(1), trans-L(2), cis
      L(2), L(3)) can recognize alkaline earth metal ions via site-selective metal
      exchange. The acyclic [L(1)Zn(3)] selectively recognizes Ca(2+), while the cyclic
      [trans-L(2)Zn(3)] showed a Ba(2+) selectivity. The metal exchange of [LZn(3)] (L
      = L(1), trans-L(2), cis-L(2), L(3)) with La(3+) efficiently occurred to give
      [LZn(2)La], but the trans-olefin linker of the [trans-L(2)Zn(2)La] significantly
      deforms the structure in such a way that one of the salicylaldoxime moieties does
      not participate in the coordination. Consequently, the chemical transformation of
      the olefinic moiety significantly affects the multimetal complexation behavior of
      the tetraoxime ligands.

PMID- 20131804
TI  - Cellular compartment model for exploring the effect of the lipidic membrane on
      the kinetics of encapsulated biochemical reactions.
AB  - One of the important characteristics of the cellular system is that interactions
      between the plasma membrane and water-soluble molecules in the cytoplasm are
      enhanced by the confinement of the molecules to the small volume of the
      intracellular space. Studying this effect in a model cell system, we measured the
      time evolution of an enzymatic hydrolysis reaction and a cell-free protein
      synthesis reaction taking place in giant liposomes having various size and
      phospholipid compositions by a flow cytometry. This single vesicle-based assay of
      a large number of liposomes enabled us to examine the volume dependence of
      enclosed reactions in detail, revealing that the presence of specific lipid
      affected the specific kinetic parameters of encapsulated reactions.

PMID- 20131805
TI  - Microwave-assisted synthesis of substituted 2-(benzylthio)imidazo[1,2a]pyrimidin
      5-ones.
AB  - A microwave-assisted solid-phase synthesis of 2
      (benzylthio)imidazo[1,2a]pyrimidin-5-ones has been developed. Using microwave
      irradiation, the reaction time was significantly reduced from a few days to 80
      min. A representative set of 10 2-(benzylthio)-6,7-substituted
      imidazo[1,2a]pyrimidin-5-ones was prepared. These compounds were subsequently N
      alkylated and formylated in good yields.

PMID- 20131806
TI  - Hydrolysis of bis(p-nitrophenyl)phosphate by tetravalent metal complexes with
      Klaui's oxygen tripodal ligand.
AB  - The treatment of HfCl(4) with NaL(OEt) (L(OEt)(-) = [(eta(5)
      C(5)H(5))Co{P(O)(OEt)(2)}(3)](-)) in nitric acid afforded L(OEt)Hf(NO(3))(3) (1).
      Hydrolysis of 1 in acetone/water (4:1, v/v) yielded the hydroxy-bridged dimer
      [(L(OEt))(2)Hf(2)(H(2)O)(4)(mu-OH)(2)][NO(3)](4) (2). The treatment of
      (NH(4))(2)[Ce(NO(3))(6)] with 2 equiv of NaL(OEt) in water afforded
      (L(OEt))(2)Ce(NO(3))(2) (3), whereas that with 1 equiv of NaL(OEt) in CH(2)Cl(2)
      gave L(OEt)Ce(NO(3))(3) (4). While 4 is stable in organic solvents such as
      acetone, it was converted completely to 3 in acetone/water. The treatment of 3
      with bis(p-nitrophenyl)phosphate (BNPP) afforded (L(OEt))(2)Ce[eta(1)
      OPO(OR)(2)](2) (5; R = p-NO(2)C(6)H(4)), whereas the reaction of 4 with
      NaPO(2)(OR)(2) yielded dinuclear [L(OEt)Ce(NO(3))(2){mu-O(2)P(OR)(2)}](2) [R = p
      NO(2)C(6)H(4) (6), Ph (7)]. The addition of 3 in acetone to an aqueous solution
      of NaH(2)PO(4) yielded the cerium(IV) dihydrogen phosphate complex
      (L(OEt))(2)Ce(PO(4)H(2))(2) (8). Complexes 1-5 and 7 have been characterized by X
      ray crystallography. The hydrolysis of BNPP with L(OEt)M(NO(3))(3) (M = Zr, Hf,
      Ce) in acetone/water has been studied by (1)H NMR spectroscopy. At 25 degrees C,
      with [Ce] = 20[BNPP], in an acetone-d(6)/N-(2-hydroxyethyl)piperazine-N'-2
      ethanesulfonic acid (4:1, v/v) buffer solution (50 mM) (4:1, v/v), the hydrolysis
      of BNPP with 4 was found to exhibit first-order kinetics with a rate constant of
      (1.1 +/- 0.1) x 10(-3) s(-1).

PMID- 20131807
TI  - Anthocyanins in purple-orange carrots (Daucus carota L.) do not influence the
      bioavailability of beta-carotene in young women.
AB  - Purple carrots contain anthocyanins in addition to the provitamin A carotenoids
      in typical orange carrots. Simultaneous consumption of these phytochemicals in
      carrots may affect the bioavailability of carotenoids. The bioavailability of
      beta-carotene in humans was assessed from an acute feeding of orange (OC) and
      purple (PC) carrots with white (WC) as a control. Carrot smoothies were served to
      female subjects (n = 5, aged 21-26 years) for breakfast after 1 week on a low
      carotenoid diet and overnight fast. OC and PC smoothies were equalized to 10.3 mg
      of all-trans beta-carotene. Plasma beta-carotene was measured for 144 h following
      treatments. Peak plasma concentrations of OC and PC treatments did not differ.
      The PC treatment 0-144 h area-under-the-curve for beta-carotene was 76% of the OC
      treatment (P < 0.05). However, when the first 24 h were compared, OC and PC
      treatments did not differ, suggesting that anthocyanins in purple carrots do not
      affect the absorption of beta-carotene postprandially.

PMID- 20131808
TI  - Evaluation of anti-invasion effect of resveratrol and related methoxy analogues
      on human hepatocarcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is
      also highly metastatic. Metastasis is considered to be the major cause of death
      in cancer patients. Resveratrol (3,5,4'-trihydroxystilbene) and related analogues
      have been reported as candidates to prevent cancer growth and invasion. The
      bioactivity of resveratrol-related analogues could be altered due to the presence
      and positioning of methoxy groups on the basic resveratrol chemical structure.
      This study investigated the effects and mechanism of action of resveratrol and
      its methoxy analogues on invasion of human hepatocarcinoma cells. The migratory
      and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and
      PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by
      treatment with resveratrol and 3,5,4'-trimethoxy-trans-stilbene (MR-3). Upon
      incubation of PMA-treated HepG2 cells with resveratrol (0-50 microM) or MR-3 (0
      50 microM), the MMP-9 activity decreased but TIMP-1 protein increased in a dose
      dependent manner. With resveratrol (0-50 microM) or MR-3 (0-1 microM) treatment
      on PMA-untreated Hep3B cells, both of the MMP-9 and MMP-2 activities decreased
      but TIMP-2 protein increased in a dose-dependent manner. These results suggest
      that resveratrol and its related methoxy analogue MR-3 might exert anti-invasive
      activity against hepatoma cells through regulation of MMP-2, MMP-9, TIMP-1, and
      TIMP-2. Further analysis with semiquantitative RT-PCR showed that the regulation
      of MMP-9 and TIMP-2 expressions by resveratrol and MR-3 in hepatoma cells may be
      on the transcriptional level but on the translational or post-translational level
      for TIMP-1.

PMID- 20131809
TI  - Spin canting and slow relaxation in a 3D pillared nickel-organic framework.
AB  - A 3D nickel-organic framework formulated as {[Ni(2)(fum)(2)(bpt)(2)(H(2)O)] x 3
      H(2)O}(n) (1), built from a mixed fumaric ion (fum), 1H-3,5-bis(4-pyridyl)-1,2,4
      triazole (bpt), and nickel salt, has been hydrothermally synthesized and
      characterized. Compound 1, having a Ni-fum chain structure in which the chains
      are pillared by the bpt spacers in a 3D "brick-wall"-like architecture, exhibits
      canted antiferromagnetism at 5.0 K. Below this temperature, slow relaxation is
      observed from the alternating-current susceptibility measurements corresponding
      to the spin-glass-like behavior.

PMID- 20131810
TI  - Self-aligned nanoscale SQUID on a tip.
AB  - A nanometer-sized superconducting quantum interference device (nanoSQUID) is
      fabricated on the apex of a sharp quartz tip and integrated into a scanning SQUID
      microscope. A simple self-aligned fabrication method results in nanoSQUIDs with
      diameters down to 100 nm with no lithographic processing. An aluminum nanoSQUID
      with an effective area of 0.034 microm2 displays flux sensitivity of 1.8 x 10(-6)
      Phi(0)/Hz(1/2) and operates in fields as high as 0.6 T. With projected spin
      sensitivity of 65 micro(B)/Hz(1/2) and high bandwidth, the SQUID on a tip is a
      highly promising probe for nanoscale magnetic imaging and spectroscopy.

PMID- 20131811
TI  - Isolation, characterization, and computational studies of the novel [Mo3(mu3
      Br)2(mu-Br)3Br6]2- cluster anion.
AB  - The novel trimolybdenum cluster [Mo(3)(mu(3)-Br)(2)(mu-Br)(3)Br(6)](2-) (1,
      {Mo(3)}(9+), 9 d-electrons) has been isolated from the reaction of [Mo(CO)(6)]
      with 1,2-C(2)H(4)Br(2) in refluxing PhCl. The compound has been characterized in
      solution by electrospray ionization mass spectrometry (ESI-MS), UV-vis
      spectroscopy, cyclic voltammetry, and in the solid state by X-ray analysis
      (counter-cations: (n-Bu)(4)N(+) (1), Et(4)N(+), Et(3)BzN(+)), electron
      paramagnetic resonance (EPR), magnetic susceptibility measurements, and infrared
      spectroscopy. The least disordered (n-Bu)(4)N(+) salt crystallizes in the
      monoclinic space group C2/c, a = 20.077(2) A, b = 11.8638(11) A, c = 22.521(2) A,
      alpha = 90 deg, beta = 109.348(4) deg, gamma = 90 deg, V = 5061.3(9) A(3), Z = 4
      and contains an isosceles triangular metal arrangement, which is capped by two
      bromine ligands. Each edge of the triangle is bridged by bromine ions. The
      structure is completed by six terminal bromine ligands. According to the magnetic
      measurements and the EPR spectrum the trimetallic core possesses one unpaired
      electron. Electrochemical data show that oxidation by one electron of 1 is
      reversible, thus proceeding with retention of the trimetallic core, while the
      reduction is irreversible. The effective magnetic moment of 1 (mu(eff), 1.55
      mu(B), r.t.) is lower than the spin-only value (1.73 mu(B)) for S = 1/2 systems,
      most likely because of high spin-orbit coupling of Mo(III) and/or magnetic
      coupling throughout the lattice. The ground electronic state of 1 was studied
      using density functional theory techniques under the broken symmetry formalism.
      The ground state is predicted to exhibit strong antiferromagnetic coupling
      between the three molybdenum atoms of the core. Moreover, our calculated data
      predict two broken symmetry states that differ only by 0.4 kcal/mol (121 cm(-1)).
      The antiferromagnetic character is delocalized over three magnetic orbitals
      populated by three electrons. The assignment of the infrared spectra is also
      provided.

PMID- 20131812
TI  - Vertical InAs nanowire wrap gate transistors with f(t) > 7 GHz and f(max) > 20
      GHz.
AB  - In this letter we report on high-frequency measurements on vertically standing
      III-V nanowire wrap-gate MOSFETs (metal-oxide-semiconductor field-effect
      transistors). The nanowire transistors are fabricated from InAs nanowires that
      are epitaxially grown on a semi-insulating InP substrate. All three terminals of
      the MOSFETs are defined by wrap around contacts. This makes it possible to
      perform high-frequency measurements on the vertical InAs MOSFETs. We present S
      parameter measurements performed on a matrix consisting of 70 InAs nanowire
      MOSFETs, which have a gate length of about 100 nm. The highest unity current gain
      cutoff frequency, f(t), extracted from these measurements is 7.4 GHz and the
      maximum frequency of oscillation, f(max), is higher than 20 GHz. This
      demonstrates that this is a viable technique for fabricating high-frequency
      integrated circuits consisting of vertical nanowires.

PMID- 20131813
TI  - Mapping atomic contact between pentacene and a Au surface using scanning
      tunneling spectroscopy.
AB  - We mapped spatially varying intramolecular electronic structures on a pentacene
      gold interface using scanning tunneling spectroscopy. Along with ab initio
      calculations based on density functional theory, we found that the directional
      nature of the d orbitals of Au atoms plays an important role in the interaction
      at the pentacene-gold contact. The gold-induced interface states are broadened
      and shifted by various pentacene-gold distances determined by the various
      registries of a pentacene molecule on a gold substrate.

PMID- 20131814
TI  - Cyanolide A, a glycosidic macrolide with potent Molluscicidal activity from the
      Papua New Guinea cyanobacterium Lyngbya bouillonii.
AB  - Over the last 50 years, molluscicides have played a critical role in the control
      of schistosomiasis transmission. Cyanolide A (2), isolated from extracts of a
      Papua New Guinea collection of Lyngbya bouillonii, is a new and highly potent
      molluscicidal agent against the snail vector Biomphalaria glabrata (LC(50) = 1.2
      microM). The structure of cyanolide A (2) was elucidated through extensive NMR
      spectroscopic analyses, yielding a symmetrical dimer that represents the newest
      addition to the family of glycosidic macrolides from cyanobacteria.

PMID- 20131815
TI  - Two-step alkylation of single-walled carbon nanotubes: substituent effect on
      sidewall functionalization.
AB  - A two-step alkylation of single-walled carbon nanotubes was investigated. The
      functionalized SWNTs were characterized with vis-NIR and Raman spectrometers,
      scanning electron microscope, and thermogravimetric analysis. This one-pot
      alkylation of SWNTs with alkyllithium followed by alkyl halide is useful for the
      sidewall functionalization of SWNTs. This reaction shows significant substituent
      effects on the degree of functionalization of SWNTs. The degree of
      functionalization on SWNTs sidewall upon SWNTs may influence their characteristic
      properties on SWNTs sidewall by the substituent effects.

PMID- 20131816
TI  - Nano-combinatorial chemistry strategy for nanotechnology research.

PMID- 20131817
TI  - "Clicktophycin-52": a bioactive cryptophycin-52 triazole analogue.
AB  - An endocyclic trans-amide linkage within the macrocyclic antitumor agent
      cryptophycin-52 was replaced by a 1,4-disubstituted 1H-1,2,3-triazole ring.
      Macrocyclisation of the triazole analogue was accomplished by macrolactamization
      as well as by Cu(I)-mediated "click"-cyclization. Compared to cryptophycin-52, in
      vitro cytotoxicity of "clicktophycin-52" against the multidrug resistant human
      cancer cell line KB-V1 is only slightly reduced.

PMID- 20131818
TI  - Efficient discovery of fluorescent chemosensors based on a biarylpyridine
      scaffold.
AB  - The discovery of several fluorescent chemosensors for Hg(II) and Ag(I) in mixed
      aqueous solution is reported. The ease with which these fluorionophores were
      prepared from a common core underscores the utility of conformational restriction
      as a signaling mechanism. In addition, for the first time, significant changes
      were observed in biarylpyridine emission wavelength, allowing ratiometric
      detection of Hg(II) and Ag(I). Finally, on the basis of computational analyses,
      beneficial structural modifications were predicted for the next generation of
      chemosensors.

PMID- 20131819
TI  - Asymmetric binary-acid catalysis with chiral phosphoric acid and MgF(2):
      catalytic enantioselective Friedel-Crafts reactions of beta,gamma-unsaturated
      alpha-ketoesters.
AB  - A unique binary chiral phosphoric acid 1a/MgF(2) catalyst that enables effective
      catalysis of asymmetric Friedel-Crafts reactions of phenols with up to 82% yield
      and >99% ee is presented. A dramatic synergistic effect has been observed in the
      combinations of two types of acids, wherein a highly active binary-acid catalyst
      can be generated from two individually inert acids.

PMID- 20131820
TI  - C(3)-symmetric chiral trisimidazoline: design and application to organocatalyst.
AB  - C(3)-symmetric chiral trisimidazoline was designed and synthesized as a new entry
      of organocatalyst with the concept of constructing C(3)-symmetric molecules with
      three C(2)-symmetric chiral components, and the application of this novel
      catalyst to asymmetric conjugate addition of beta-ketoesters to nitroolefins was
      described.

PMID- 20131821
TI  - Tetra-ortho-substituted biaryls through palladium-catalyzed Suzuki-Miyaura
      couplings with a diaminochlorophosphine ligand.
AB  - A palladium complex derived from a sterically hindered diaminochlorophosphine
      allowed for Suzuki-Miyaura cross-couplings of chloroarenes with ample scope and
      provided access to tetra-ortho-substituted bi(hetero)aryls.

PMID- 20131822
TI  - Nitrous oxide emissions from the gulf of Mexico hypoxic zone.
AB  - The production of nitrous oxide (N(2)O), a potent greenhouse gas, in hypoxic
      coastal zones remains poorly characterized due to a lack of data, though large
      nitrogen inputs and deoxygenation typical of these systems create the potential
      for large N(2)O emissions. We report the first N(2)O emission measurements from
      the Gulf of Mexico Hypoxic Zone (GOMHZ), including an estimate of the emission
      "pulse" associated with the passage of Tropical Storm Edouard in August, 2008.
      Prestorm emission rates (25-287 nmol m(-2) hr(-1)) and dissolved N(2)O
      concentrations (5 - 30 nmol L(-1)) were higher than values reported for the
      Caribbean and western Tropical Atlantic, and on the lower end of the range of
      observations from deeper coastal hypoxic zones. During the storm, N(2)O rich
      subsurface water was mixed upward, increasing average surface concentrations and
      emission rates by 23% and 61%, respectively. Approximately 20% of the N(2)O
      within the water column vented to the atmosphere during the storm, equivalent to
      13% of the total "hypoxia season" emission. Relationships between N(2)O, NO(3)(
      ), and apparent oxygen utilization (AOU) suggest enhanced post storm N(2)O
      production, most likely in response to reoxygenation of the water column and
      redistribution of organic nitrogen. Our results indicate that mixing related
      emissions contribute significantly to total seasonal emissions and must therefore
      be included in emission models and inventories for the GOMHZ and other shallow
      coastal hypoxic zones.

PMID- 20131823
TI  - Organocatalytic asymmetric formal [4 + 2] cycloaddition for the synthesis of
      spiro[4-cyclohexanone-1,3'-oxindoline] derivatives in high optical purity.
AB  - A bifunctional organocatalytic asymmetric formal [4 + 2] cycloaddition reaction
      of Nazarov reagents and methyleneindolinones afforded spiro[4-cyclohexanone-1,3'
      oxindoline] derivatives with excellent enantioselectivity (up to 98% ee).

PMID- 20131824
TI  - Tailored electroactive and quantitative ligand density microarrays applied to
      stem cell differentiation.
AB  - The ability to precisely control the interactions between materials and mammalian
      cells at the molecular level is crucial to understanding the fundamental chemical
      nature of how the local environment influences cellular behavior as well as for
      developing new biomaterials for a range of biotechnological and tissue
      engineering applications. In this report, we develop and apply for the first time
      a quantitative electroactive microarray strategy that can present a variety of
      ligands with precise control over ligand density to study human mesenchymal stem
      cell (hMSC) differentiation on transparent surfaces with a new method to
      quantitate adipogenic differentiation. We found that both the ligand composition
      and ligand density influence the rate of adipogenic differentiation from hMSC's.
      Furthermore, this new analytical biotechnology method is compatible with other
      biointerfacial characterization technologies (surface plasmon resonance, mass
      spectrometry) and can also be applied to investigate a range of protein-ligand or
      cell-material interactions for a variety of systems biology studies or cell
      behavior based assays.

PMID- 20131825
TI  - Molecular electrocatalysis for oxygen reduction by cobalt porphyrins adsorbed at
      liquid/liquid interfaces.
AB  - Molecular electrocatalysis for oxygen reduction at a polarized water/1,2
      dichloroethane (DCE) interface was studied, involving aqueous protons, ferrocene
      (Fc) in DCE and amphiphilic cobalt porphyrin catalysts adsorbed at the interface.
      The catalyst, (2,8,13,17-tetraethyl-3,7,12,18-tetramethyl-5-p-amino
      phenylporphyrin) cobalt(II) (CoAP), functions like conventional cobalt
      porphyrins, activating O(2) via coordination by the formation of a superoxide
      structure. Furthermore, due to the hydrophilic nature of the aminophenyl group,
      CoAP has a strong affinity for the water/DCE interface as evidenced by
      lipophilicity mapping calculations and surface tension measurements, facilitating
      the protonation of the CoAP-O(2) complex and its reduction by ferrocene. The
      reaction is electrocatalytic as its rate depends on the applied Galvani potential
      difference between the two phases.

PMID- 20131826
TI  - Encapsulation and stabilization of gold nanoparticles with "click"
      polyethyleneglycol dendrimers.
AB  - Water-soluble arene-cored "clicked" and non-"clicked" dendrimers terminated by
      27, 81, and 243 triethyleneglycol (TEG) tethers (respectively generations G0, G1,
      and G2) have been synthesized and shown to form dendrimer-encapsulated gold
      nanoparticles (DEAuNPs) and dendrimer-stabilized gold nanoparticles (DSAuNPs).
      The dendrimers have been characterized by IR, (1)H NMR, (13)C NMR, size-exclusion
      chromatography, elemental analysis, MALDI-TOF mass spectroscopy, DOSY NMR, and
      dynamic light scattering. The AuNPs have been generated and stabilized by these
      PEGylated dendrimers using a variety of reduction modes, including NaBH(4) in
      methanol, various single-electron metallocene-type reductants, and even in the
      absence of additional reductants. The active role of the "clicked" triazole
      rings, dendrimer generation, stoichiometry of Au precursor, and nature of the
      reductant and of the solvent are delineated, leading to DSAuNPs with the G0
      dendrimer and smaller DEAuNPs with the G1 and G2 dendrimers. Altogether, AuNPs in
      the size range from 1.8 to 42 nm were formed and characterized by transmission
      electron microscopy (TEM), high resolution TEM (HRTEM) and UV-vis spectroscopy.
      Both 1,2,3-triazole and PEGylated Percec-type dendrons are required in the
      dendrimer structure for the stabilization of AuNPs upon NaBH(4) reduction of
      HAuCl(4) in methanol. On the other hand, in the absence of other reductant in
      water, only PEGylated Percec-type dendrons in dendrimers were found to be
      indispensable, because of their semicavitand shape, for the spontaneous reduction
      of HAuCl(4) and stabilization of DSAuNPs.

PMID- 20131827
TI  - Acyl phosphonates: good hydrogen bond acceptors and ester/amide equivalents in
      asymmetric organocatalysis.
AB  - This study demonstrates that unsaturated acyl phosphonates are excellent hydrogen
      bond acceptors in enantioselective organocatalysis. By employing chiral thioureas
      or squaramides as catalysts, the acyl phosphonates are effectively coordinated
      and activated by hydrogen bonding, thereby providing successful relay of the
      chirality from the catalyst to the substrate. A variety of highly stereoselective
      conjugate additions to alpha,beta-unsaturated acyl phosphonates were performed,
      using different carbon-based nucleophiles such as oxazolones, indoles, and 1,3
      dicarbonyl compounds. The reaction concept has been developed to be a double
      nucleophilic reaction, and it is shown that the acyl phosphonates serve as masked
      ester or amide equivalents, which upon quenching with the second nucleophile
      generate the parent structures in situ. Accordingly, formal C-C bond formation
      reactions of ester and amide substrates are achieved, affording a broad spectrum
      of optically active conjugate adducts in good yields and excellent
      enantioselectivities. Based on the experimental results, the mechanisms for the
      different reactions are discussed, including the approach of the oxazolones,
      indoles, and 1,3-dicarbonyl compounds to the acyl phosphonate coordinated to the
      catalyst and the role of the catalyst for the reaction course of the
      nucleophiles.

PMID- 20131828
TI  - Transmetalation of Z-telluroenynes: stereoselective synthesis of Z-enynols and
      their application in palladium-catalyzed cyclization.
AB  - The synthesis of various Z-enynols via reaction of vinyllithium intermediate with
      aldehydes and ketones is described. The subsequent cyclization of a wide variety
      of Z-enynols afforded substituted furans and dihydrofurans with high
      regioselectivity under mild reaction conditions.

PMID- 20131829
TI  - Novel layered hybrid fluoroaluminate in the composition space diagram of the
      Al(OH)3-HguaCl-HF(aq)-EtOH system.
AB  - A composition space diagram is used to establish the stability regions of hybrid
      fluoroaluminates synthesized by solvothermal reactions in the Al(OH)(3)-HguaCl
      HF(aq)-EtOH system. The syntheses are conducted using microwave heating at 190
      degrees C for 1 h. The structures of two new guanidinium fluoroaluminates,
      (H(3)O)(2) x [Hgua](16) x (Al(4)F(18))(3) x H(2)O and [Hgua](2) x (Al(5)F(17)),
      are reported. (H(3)O)(2) x [Hgua](16) x (Al(4)F(18))(3) x H(2)O, determined from
      single-crystal X-ray data, consists of discrete (Al(4)F(18))(6-) polyanions,
      while [Hgua](2) x (Al(5)F(17)), solved from powder X-ray diffraction data in
      direct space, contains unprecedented Al(5)F(17) layers constructed from the
      intergrowth of HTB and perovskite columns. A disorder of H(2)O and H(3)O(+) is
      evidenced in (H(3)O)(2) x [Hgua](16) x (Al(4)F(18))(3) x H(2)O together with a
      disorder of guanidinium cations in the interlayer space of [Hgua](2) x
      (Al(5)F(17)).

PMID- 20131830
TI  - Structures and phase transitions in (MoO2)2P2O7.
AB  - We report structural investigations into (MoO(2))(2)P(2)O(7) using a combination
      of X-ray, neutron and electron diffraction, and solid-state NMR supported by
      first principles quantum chemical calculations. These reveal a series of phase
      transitions on cooling at temperatures of 377 and 325 K. The high temperature
      gamma-phase has connectivity consistent with that proposed by Kierkegaard at room
      temperature (but with improved bond length distribution), and contains 13 unique
      atoms in space group Pnma with lattice parameters a = 12.6577(1) A, b = 6.3095(1)
      A, c = 10.4161(1) A, and volume 831.87(1) A(3) from synchrotron data at 423 K.
      The low temperature alpha-structure was indexed from electron diffraction data
      and contains 60 unique atoms in space group P2(1)/c with cell parameters a =
      17.8161(3) A, b = 10.3672(1) A, c = 17.8089(3) A, beta = 90.2009(2) degrees, and
      volume 3289.34(7) A(3) at 250 K. First principles calculations of (31)P chemical
      shift and J couplings were used to establish correlation between local structure
      and observed NMR parameters, and 1D and 2D (31)P solid-state NMR used to validate
      the proposed crystal structures. The intermediate beta-phase is believed to adopt
      an incommensurately modulated structure; (31)P NMR suggests a smooth structural
      evolution in this region.

PMID- 20131831
TI  - General synthesis of 2D ordered hollow sphere arrays based on nonshadow
      deposition dominated colloidal lithography.
AB  - A general strategy, nonshadow deposition dominated colloidal lithography (NSCL),
      was proposed for the synthesis of two-dimensional (2D) ordered hollow sphere
      arrays of conductive materials. Gold, polypyrrole, CdS, and ZnO were taken as
      model materials to demonstrate the NSCL strategy, and built as 2D hollow sphere
      arrays successfully. In this strategy, a thin gold coating is first introduced on
      a polystyrene sphere (PS) colloidal monolayer via ion-sputtering deposition, and
      a hollow sphere array can thus be obtained by further electrochemical deposition
      on such a monolayer and by subsequent removal of PSs. The proposed strategy is
      flexible and facile to control the microstructure and size of the hollow sphere
      array, and the features are as follows: (i) controllable shell of the hollow
      sphere from single-layer to multilayer with single or multiple compositions, (ii)
      tunable morphology from simple structure to hierarchical micro/nanostructure, and
      (iii) changeable arrangement of hollow spheres from close-packing to non-close
      packing. Besides these, the hollow sphere size and the shell thickness can also
      be controlled by changing the colloidal sphere and deposition time, respectively.
      Further investigation indicates that the success of NSCL should be owed to a key
      step, that is, an ion-sputtering induced nonshadow deposition surrounding the
      whole surfaces of colloidal spheres. This allows an equipotential face and thus
      homogeneous deposition surrounding the surfaces of PSs in an electrochemical
      deposition process, and final formation of hollow sphere structure. The 2D
      ordered hollow sphere arrays with controllable microstructure and size could
      exhibit importance both in fundamental research and in practical applications.

PMID- 20131832
TI  - Surface plasmon resonance on gold and silver films coated with thin layers of
      amorphous silicon-carbon alloys.
AB  - The paper reports on a novel surface plasmon resonance (SPR) substrate
      architecture based on the coating of a gold (Au) or silver (Ag) substrate with 5
      nm thin amorphous silicon-carbon alloy films. Ag/a-Si(1-x)C(x):H and Au/a-Si(1
      x)C(x):H multilayers are found to provide a significant advantage in terms of
      sensitivity over both Ag and Au for SPR refractive index sensing. The possibility
      for the subsequent linking of stable organic monolayers through Si-C bonds is
      demonstrated. In a proof-of-principle experiment that this structure can be used
      for real-time biosensing experiments, amine terminated biotin was covalently
      linked to the acid-terminated SPR surface and the specific streptavidin-biotin
      interaction recorded.

PMID- 20131833
TI  - Topotactic reduction of YBaCo2O5 and LaBaCo2O5: square-planar Co(I) in an
      extended oxide.
AB  - The low-temperature reduction of YBaCo(2)O(5) and LaBaCo(2)O(5) with NaH to form
      YBaCo(2)O(4.5) and YBaCo(2)O(4.25), respectively, demonstrates that the
      structures of anion-deficient materials formed by such topotactic reductions can
      be directed by the ordering and identity of the A-site cations. YBaCo(2)O(4.5)
      adopts a structure consisting of a corner-shared network of square-based
      pyramidal CoO(5) and distorted tetrahedral CoO(4) units. The structure of
      LaBaCoO(4.25) is more complex, consisting of an array of square-based pyramidal
      CoO(5), distorted tetrahedral CoO(4), and square planar CoO(4) units. Magnetic
      susceptibility and variable-temperature neutron diffraction data reveal that
      YBaCo(2)O(4.5) adopts a G-type antiferromagnetically ordered structure below T(N)
      approximately 280 K. LaBaCo(2)O(4.25) also adopts antiferromagnetic order (T(N)
      approximately 325 K) with ordered moments consistent with the presence of square
      planar, low-spin, s = 0, Co(I) centers. A detailed analysis reveals that the
      different anion vacancy ordered structures adopted by the two REBaCo(2)O(5-x)
      phases are directed by the relative sizes and ordering of the La(3+) and Y(3+)
      cations. This suggests that ordered arrangements of A-cations can be used to
      direct the anion vacancy order in topotactically reduced phases, allowing the
      preparation of novel metal-oxygen networks containing unusual transition metal
      coordination environments.

PMID- 20131834
TI  - Intracellular delivery of a membrane-impermeable enzyme in active form using
      functionalized gold nanoparticles.
AB  - Gold nanoparticles were coated with a short peptide to promote intracellular
      delivery of membrane-impermeable proteins. Through microscopy and enzyme assays,
      we demonstrated the particles were able to transport functional enzymes into a
      variety of cell lines. Significantly, the transported proteins were able to
      escape from endosomes. Moreover, these particles showed no apparent cytotoxicity.

PMID- 20131835
TI  - Controlling comonomer distribution in random copolymers by chemical coloring of
      surface-tethered homopolymers: an insight from discontinuous molecular dynamics
      simulation.
AB  - Postpolymerization chemical modification ("coloring") of homopolymer brushes made
      of A units using B chemical moieties produces surface-anchored random copolymers
      (RCPs) A(1-x)B(x), where x is the degree of "coloring". We employ discontinuous
      molecular dynamics to study the "coloring" process in macromolecular tethers made
      of various lengths grafted at low and high densities on flat impenetrable
      surfaces. We demonstrate that the comonomer distribution in the A(1-x)B(x) RCPs
      depends on the interplay among (1) the length and the grafting density of the A
      based homopolymer anchors, (2) the solubility of the parent homopolymer, and (3)
      the solubility of the B coloring units. Chemical modification of sparsely spaced
      chains on the surface leads to nearly random comonomer distribution in the A(1
      x)B(x) RCPs regardless of the solubility of A and B. In contrast, the
      distribution of A and B units in A(1-x)B(x) RCPs prepared from homopolymers
      tethered at high grafting densities depends on the solubility of the parent
      homopolymer. Chemical modification of well-solvated A homopolymer grafts results
      in comonomer distributions that resemble those of diblock copolymers, comprising
      lightly modified blocks near the surface and heavily "colored" blocks at the top
      of the grafts. The relative lengths of the two blocks can be tuned by varying the
      solubility of B. Under poor solvent conditions, the distribution of A and B in
      the A(1-x)B(x) RCP is more complex; it is governed by the conformation of the
      parent A macromolecular anchors that form collapsed clusters before the coloring
      reaction.

PMID- 20131836
TI  - Photodegradation of novel nitromethylene neonicotinoids with tetrahydropyridine
      fixed cis configuration in aqueous solution.
AB  - Photodegradation of 1-((6-chloropyridin-3-yl)methyl)-7-methyl-8-nitro-1,2,3,5,6,7
      hexahydroimidazo[1,2-a]pyridin-5-ol (IPPA152001) and 1-((6-chloropyridin-3
      yl)methyl)-7-methyl-8-nitro-5-propoxy-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine
      (IPPA152004) was studied in distilled water; high-pressure mercury lamp and xenon
      lamp were used as light sources. The photolytic rate constants of the two
      compounds and their half-lives were calculated. Compared with imidacloprid, the
      order of photodegradation rate of three compounds was as follows: imidacloprid >
      IPPA152001 > or = IPPA152004. Mercury lamp light intensity was measured with
      chemical actinometers. The quantum yields for photodegradation of IPPA152001 and
      IPPA152004 in distilled water were also calculated. Photodegradation products of
      IPPA152004 were preliminarily identified on the basis of the spectral data of GC
      MS, LC-TOF-ESI, and LC-MS-MS in positive mode. The photodegradation pathways of
      IPPA152004 were proposed according to the structures of photoproducts.

PMID- 20131837
TI  - Nucleophilic catalysis of carbohydrate oxime formation by anilines.
AB  - Chemoselective formation of glycoconjugates from unprotected glycans is needed to
      further develop chemical biology involving glycans. Carbohydrate oxime formation
      is often slow, and organocatalysis by anilines would be highly promising. Here,
      we present that carbohydrate oxime formation can be catalyzed with up to 20-fold
      increases in overall reaction rate at 100 mM aniline. Application of this
      methodology provided access to complex glycoconjugates.

PMID- 20131838
TI  - Utilization of a factorial design to study the composting of hydrolyzed grape
      marc and vinification lees.
AB  - Hydrolyzed grape marc (HGM) is the solid residue generated after the acid
      hydrolysis of grape marc to obtain hemicellulosic sugars for biotechnological
      purposes. In this work, HGM containing cellulose and lignin was composted
      together with vinification lees to obtain plant substrates on a laboratory scale.
      The effects of temperature (in the range of 20-50 degrees C), concentration of
      vinification lees (5-100 g/100 g of hydrolyzed grape marc), and concentration of
      CaCO(3) on the final properties of the composted HGM were studied by means of an
      experimental plan with factorial structure. The interrelationship between
      dependent and operational variables was established by models including linear,
      interaction, and quadratic terms. The most influential variable on the C/N ratio
      and P, K and Mg contents of composted substrates was the vinification lees
      concentration followed by the temperature, whereas on Na content and electrical
      conductivity the most influential variable was the temperature followed by the
      vinification lees concentration. The results of the incubation experiments
      indicated that optimal conditions for obtaining plant substrates can be achieved
      by composting 1:1 mixtures of hydrolyzed grape marc and vinification lees, in the
      presence of 5 g of CaCO(3)/100 g of HGM. During composting the pH of the mixtures
      increased from 5.1-6.7 to 7.1-8.1, salinity and water-soluble carbon were reduced
      in most cases, and the initial phytotoxicity disappeared in all of the mixtures
      tested.

PMID- 20131839
TI  - Directed self-assembly of spheres into a two-dimensional colloidal crystal by
      viscoelastic stresses.
AB  - Ordering induced by shear flow can be used to direct the assembly of particles in
      suspensions. Flow-induced ordering is determined by the balance between a range
      of forces, such as direct interparticle, Brownian, and hydrodynamic forces. The
      latter are modified when dealing with viscoelastic rather than Newtonian
      matrices. In particular, 1D stringlike structures of spherical particles have
      been observed to form along the flow direction in shear thinning viscoelastic
      fluids, a phenomenon not observed in Newtonian fluids at similar particle volume
      fractions. Here we report on the formation of freestanding crystalline patches in
      planes parallel to the shearing surfaces. The novel microstructure is formed when
      particles are suspended in viscoelastic, wormlike micellar solutions and only
      when the applied shear rate exceeds a critical value. In spite of the very low
      volume fraction (less than 0.01), particles arrange themselves in 2D crystalline
      patches along the flow direction. This is a bulk phenomenon because 2D crystals
      form throughout the whole gap between plates, with the gap thickness being much
      larger than the particle size. Shear flow may hence be an easy method to drive
      particles into crystalline order in suspensions with viscoelastic properties. The
      crystalline structure reported here could be used to design new materials with
      special mechanical, optical, thermal, or electric properties.

PMID- 20131840
TI  - Isoflavones in coffee: influence of species, roast degree, and brewing method.
AB  - This paper reports the isoflavone contents of roasted coffee beans and brews, as
      influenced by coffee species, roast degree, and brewing procedure. Total
      isoflavone level is 6-fold higher in robusta coffees than in arabica ones, mainly
      due to formononetin. During roasting, the content of isoflavones decreases,
      whereas their extractability increases (especially for formononetin). Total
      isoflavones in espresso coffee (30 mL) varied from approximately 40 microg (100%
      arabica) to approximately 285 microg (100% robusta), with long espressos (70 mL)
      attaining more than double isoflavones of short ones (20 mL). Espressos (30 mL)
      prepared from commercial blends contained average amounts of 6, 17, and 78 microg
      of genistein, daidzein, and formononetin, respectively. Comparison of different
      brewing methods revealed that espresso contained more isoflavones ( approximately
      170 microg/30 mL) than a cup of press-pot coffee ( approximately 130 microg/60
      mL), less than a mocha coffee ( approximately 360 microg/60 mL), and amounts
      similar to those of a filtered coffee cup ( approximately 180 microg/120 mL).

PMID- 20131841
TI  - Tomato ( Lycopersicon esculentum ) seeds: new flavonols and cytotoxic effect.
AB  - In this study, seeds of Lycopersicon esculentum Mill. were analyzed by HPLC/UV
      PAD/MS(n)-ESI. Fourteen flavonoids were identified, including quercetin,
      kaempferol, and isorhamnetin derivatives, with 13 of them being reported for the
      first time in tomato seeds. The major identified compounds were quercetin-3-O
      sophoroside, kaempferol-3-O-sophoroside, and isorhamnetin-3-O-sophoroside. A
      significant cell proliferation inhibition (>80%), against rat basophile leukemia
      (RBL-2H3) cell line, was observed with this extract (IC(50) = 5980 microg/mL).
      For acetylcholinesterase inhibitory activity, a concentration-dependent effect
      was verified (IC(20) = 2400 microg/mL). The same behavior was noted regarding
      antioxidant capacity, evaluated against DPPH (IC(10) = 284 microg/mL), nitric
      oxide (IC(25) = 396 microg/L), and superoxide radicals (IC(25) = 3 microg/mL).

PMID- 20131842
TI  - Relationship between hydrophobicity and antioxidant ability of "phenolipids" in
      emulsion: a parabolic effect of the chain length of rosmarinate esters.
AB  - The polar paradox predicts that hydrophobic antioxidants are more active in
      emulsions than their hydrophilic homologues, thus assuming a linear dependency
      between hydrophobicity and antioxidant capacity. In contrast, we formulate in
      this paper an alternative hypothesis assuming a possible nonlinear dependency. To
      verify this so-called "nonlinear hypothesis", the antioxidant capacity of a
      homologous series of rosmarinic acid and its alkyl esters (methyl, butyl, octyl,
      dodecyl, hexadecyl, octadecyl, and eicosyl) was evaluated using a newly developed
      conjugated autoxidizable triene (CAT) assay. It appeared that the antioxidant
      capacity increases as the alkyl chain is lengthened, with a maximum for the octyl
      chain, after which further chain extension leads to a collapse in antioxidant
      capacity. This nonlinear effect was discussed in relation to the "cutoff effect"
      generally observed in studies using cultured cells. This new hypothesis may
      provide a better understanding of the antioxidant behavior of phenolics in
      emulsion which is a key to develop new antioxidant strategies to protect lipid
      substrates from oxidation. Moreover, the lipophilization with medium chain
      appeared as a promising way to enhance the antioxidant capacity of phenolics
      since octyl rosmarinate was three times more effective than rosmarinic acid which
      is already one of the most powerful known phenolic antioxidant. Finally, this
      work paves the way for systematic investigation of the chain length effect to
      design new "phenolipids" in a rational fashion.

PMID- 20131843
TI  - Michael acceptor based antiplasmodial and antitrypanosomal cysteine protease
      inhibitors with unusual amino acids.
AB  - New peptidic Michael acceptor based cysteine protease inhibitors displaying
      antiparasitic activity were identified by testing a broad series of 45 compounds
      in total, containing Asn, Gln, or Phe. As target enzymes, falcipain-2 and -3 from
      P. falciparum and rhodesain from T. b. rhodesiense were used. In the case of the
      Asn/Gln containing compounds, the trityl-protected, diastereomeric E-configured
      vinylogous dipeptide esters 16 (Boc-(S)-Phg-(R/S)-vGln(Trt)-OEt) were discovered
      as most active inhibitors concerning both protease inhibition and antiparasitic
      acitivity, with inhibition constants in the submicromolar range. The compounds
      were shown to display time-dependent and competitive inhibition. In the case of
      the Phe containing compounds, the maleic acid derivatives 42 and 43 (BnO-Phe<-
      Mal-Phe-OBn, BnO-Phe<--Mal-Phe-Ala-OBn, Mal = maleic acid) displayed good
      inhibition of rhodesain as well as good antitrypanosomal activity, while the
      fumaric acid derived E-analogue 14 (BnO-Phe<--Fum-Phe-OBn) only displayed
      inhibition of the target enzymes but no antiparasitic activity. Inhibition by
      these Phe derivatives was shown to be time-independent and competitive.

PMID- 20131844
TI  - Photooxidation and Phototoxicity of pi-extended squaraines.
AB  - This paper describes the synthesis of pi-extended squaraines and their
      photooxidation properties and gives an in-depth characterization of these
      molecules as photosensitizing agents. Squaraines show a strong absorption in the
      tissue transparency window (600-800 nm), and upon irradiation, they undergo a
      photooxidation process, leading to the formation of peroxide and hydroperoxide
      radicals according to a type I radical chain process. Confocal laser microscopy
      demonstrates that the designed squaraines efficiently internalize in the
      cytoplasm and not in the nucleus of the cell. In the dark, they are scarcely
      cytotoxic, but after irradition, they promote a strong dose-dependent phototoxic
      effect in four different cancer cells. In HeLa and MCF-7 cells, squaraines 4 and
      5, thanks to their hydrocarbon tails, associate to the membranes and induce lipid
      peroxidation, as indicated by a marked increase of malonyldialdehyde after
      photodynamic treatment, in agreement with in vitro photooxidation studies. FACS,
      caspase-3/7 assays and time-lapse microscopy demonstrate that the designed
      squaraines cause cell death primarily by necrosis.

PMID- 20131845
TI  - New substructure filters for removal of pan assay interference compounds (PAINS)
      from screening libraries and for their exclusion in bioassays.
AB  - This report describes a number of substructural features which can help to
      identify compounds that appear as frequent hitters (promiscuous compounds) in
      many biochemical high throughput screens. The compounds identified by such
      substructural features are not recognized by filters commonly used to identify
      reactive compounds. Even though these substructural features were identified
      using only one assay detection technology, such compounds have been reported to
      be active from many different assays. In fact, these compounds are increasingly
      prevalent in the literature as potential starting points for further exploration,
      whereas they may not be.

PMID- 20131846
TI  - Vinylcatechin dimers are much better copigments for anthocyanins than catechin
      dimer procyanidin b3.
AB  - The binding constants (K) for the interaction of three copigments (CP), two
      epimeric vinylcatechin dimers (CP1 and CP2), and catechin dimer B3 (CP3) with two
      pigments, malvidin-3-glucoside (oenin) and malvidin-3,5-diglucoside (malvin),
      were determined. The K values clearly show that both vinylcatechin dimers have
      much higher affinity for oenin and malvin than dimer B3: K(CP2) > K(CP1) >>
      K(CP3). Quantum mechanics and molecular dynamics calculations were also performed
      to interpret the binding data and specify the relative arrangement of the pigment
      and copigment molecules within the complexes.

PMID- 20131848
TI  - Inhibiting intramolecular electron transfer in flavin adenine dinucleotide by
      host-guest interaction: a fluorescence study.
AB  - Modulation in the photophysical properties and intramolecular electron transfer
      behavior of the flavin adenine dinucleotide (FAD) molecule has been investigated
      in the presence of the macrocyclic hosts, alpha-, beta- and gamma-cyclodextrins
      (CDs), using absorption and steady-state and time-resolved fluorescence
      measurements. The results demonstrate that only the beta-CD host has a suitable
      cavity dimension to form a weak inclusion complex with FAD by encapsulating the
      adenine moiety, which is the preferred binding site in the large FAD molecule.
      Interestingly, in spite of the weak binding interaction, a significant
      enhancement in the fluorescence intensity of FAD is observed on complexation with
      beta-CD, and this has been attributed mainly to the modulation in the
      conformational dynamics of FAD in the presence of beta-CD. In aqueous solutions,
      a good fraction of FAD molecules exist in a "closed" conformation with the
      adenine and isoalloxazine rings stacked on each other, thus leading to very
      efficient fluorescence quenching due to the ultrafast intramolecular electron
      transfer from adenine to the isoalloxazine moiety. Complex formation with beta-CD
      inhibits this intramolecular electron transfer by changing the "closed"
      conformation of FAD to the "open" form, wherein the adenine and isoalloxazine
      moieties are widely separated, thus prohibiting the fluorescence quenching
      process. Further evidence for the conformational changes has been obtained by the
      observation of a long lifetime component in the fluorescence decay of FAD in the
      presence of beta-CD, which corresponds to the decay of the unquenched "open" form
      of FAD. Fluorescence up-conversion studies also indicate the absence of any
      ultrafast component in the fluorescence decay arising from the complexed FAD,
      thus supporting the formation of the "open" form in the presence of beta-CD, with
      no intramolecular electron transfer.

PMID- 20131849
TI  - Multiphoton-excited luminescent lanthanide bioprobes: two- and three-photon cross
      sections of dipicolinate derivatives and binuclear helicates.
AB  - Multiphoton excited luminescent properties of water-soluble Eu(III) and Tb(III)
      complexes with derivatives of dipicolinic acid functionalized with a
      polyoxyethylene pendant arm and terminal groups, [Eu(L(OMe))(3)](3-),
      [Eu(L(NH2))(3)](3-), and [Tb(L(OH))(3)](3-), as well as of binuclear helicates
      with overall composition [Ln(2)(L(CX))(3)] (X = 2, 5) are investigated.
      Characteristic emission from the (5)D(0) and (5)D(4) excited levels of Eu(III)
      and Tb(III), respectively, upon approximately 800 nm excitation results from
      three-photon absorption (3PA) for [Eu(L(OMe))(3)](3-), [Eu(L(NH2))(3)](3-),
      [Tb(L(OH))(3)](3-), and [Ln(2)(L(C2))(3)], while luminescence from
      [Eu(2)(L(C5))(3)] is induced by two-photon absorption (2PA) owing to its 1PA
      spectrum extending further into the visible. The 3PA cross sections have been
      determined and are the first ones reported for lanthanide complexes: (i) those of
      Eu(III) and Tb(III) bimetallic helicates [Ln(2)(L(C2))(3)] are 20 times larger
      compared to the corresponding values for tris(dipicolinates); (ii) derivatization
      of dipicolinic acid for Tb(III) complexes has almost no influence on the 3PA
      cross section; however, for Eu(III) complexes a approximately 2 times decrease is
      observed. The feasibility of [Eu(2)(L(C5))(3)] as multiphoton luminescence
      bioprobe is demonstrated by two-photon scanning microscopy imaging experiments on
      HeLa cells incubated with this bimetallic helicate.

PMID- 20131850
TI  - Hydroxyl radical substitution in halogenated carbonyls: oxalic acid formation.
AB  - An ab initio study of OH radical substitution reactions in halogenated carbonyls
      is conducted. Hydroxyl radical substitution into oxalyl dichloride [ClC(O)C(O)Cl]
      and oxalyl dibromide [BrC(O)C(O)Br], resulting in the formation of oxalic acid,
      is presented. Analogous substitution reactions in formyl chloride [ClCH(O)],
      acetyl chloride [ClC(O)CH(3)], formyl bromide [BrCH(O)], and acetyl bromide
      [BrC(O)CH(3)] are considered. Energetics of competing hydrogen abstraction
      reactions for all applicable species are computed for comparison. Geometry
      optimizations and frequency computations are performed using the second-order
      Moller-Plesset perturbation theory (MP2) and the 6-31G(d) basis set for all
      minimum species and transition states. Single point energy computations are
      performed using fourth-order Moller-Plesset perturbation theory (MP4) and coupled
      cluster theory [CCSD(T)]. Potential energy surfaces, including activation
      energies and enthalpies, are determined from the computations. These potential
      energy surfaces show that OH substitution into ClC(O)C(O)Cl and BrC(O)C(O)Br,
      resulting in the formation of oxalic acid and other minor products, is
      energetically favorable. Energetics of analogous reactions with ClCH(O), BrCH(O),
      ClC(O)CH(3), and BrC(O)CH(3) are also computed.

PMID- 20131852
TI  - Strong piezoelectricity in bioinspired peptide nanotubes.
AB  - We show anomalously strong shear piezoelectric activity in self-assembled
      diphenylalanine peptide nanotubes (PNTs), indicating electric polarization
      directed along the tube axis. Comparison with well-known piezoelectric LiNbO(3)
      and lateral signal calibration yields sufficiently high effective piezoelectric
      coefficient values of at least 60 pm/V (shear response for tubes of approximately
      200 nm in diameter). PNTs demonstrate linear deformation without irreversible
      degradation in a broad range of driving voltages. The results open up a wide
      avenue for developing new generations of "green" piezoelectric materials and
      piezonanodevices based on bioactive tubular nanostructures potentially compatible
      with human tissue.

PMID- 20131853
TI  - Plasmonic modes of metallic semishells in a polymer film.
AB  - The symmetry-broken geometry and variation of metal composition of semishells
      induce new plasmonic properties. A system of separated metallic semishells
      embedded in a poly(dimethylsiloxane) polymer film provides an ideal platform to
      investigate the localized surface plasmon resonance modes of semishells. We
      demonstrate experimentally that silver, gold, copper, and aluminum semishells can
      offer distinct plasmonic responses due to the wide range of their material
      parameters. Numerical calculations combined with the plasmon hybridization theory
      render us a clear understanding and assignment of the plasmonic modes of the
      semishells.

PMID- 20131854
TI  - High optical absorption of indium sulfide nanorod arrays formed by glancing angle
      deposition.
AB  - Indium(III) sulfide has recently attracted much attention due to its potential in
      optical sensors as a photoconducting material and in photovoltaic applications as
      a wide band gap material. On the other hand, optical absorption properties are
      key parameters in developing photosensitive photodetectors and efficient solar
      cells. In this work, we show that indium sulfide nanorod arrays produced by the
      glancing angle deposition technique have superior absorption and low reflectance
      properties compared to conventional flat thin film counterparts. We observed an
      optical absorption value of approximately 96% for nanorods at wavelengths <500 nm
      in contrast to 79% for conventional thin films of indium sulfide. A superior
      photoconductivity (PC) response as high as about 40% (change in resistance upon
      illumination) was also observed in nanorod samples. This is mainly believed to be
      due to their high optical absorption, whereas only less than 1% PC change was
      detected in conventional thin films. We give a preliminary description of the
      enhanced light absorption properties of the nanorods by using the Shirley-George
      model, which predicts diffusion of light as a function of the roughness of the
      surface.

PMID- 20131855
TI  - Influence of alumina type on the evolution and activity of alumina-supported Fe
      catalysts in single-walled carbon nanotube carpet growth.
AB  - We have studied the lifetime, activity, and evolution of Fe catalysts supported
      on different types of alumina: (a) sputter deposited alumina films
      (sputtered/Fe), (b) electron-beam deposited alumina films (e-beam/Fe), (c)
      annealed e-beam deposited alumina films (annealed e-beam/Fe), (d) alumina films
      deposited by atomic layer deposition (ALD/Fe), and (e) c-cut sapphire
      (sapphire/Fe). We show that the catalytic behavior, Ostwald ripening, and
      subsurface diffusion rates of Fe catalyst supported on alumina during water
      assisted growth or "supergrowth" of single-walled carbon nanotube (SWNT) carpets
      are strongly influenced by the porosity of the alumina support. The catalytic
      activity increases in the following order: sapphire/Fe < annealed e-beam/Fe <
      ALD/Fe < e-beam/Fe < sputtered/Fe. With a combination of microscopic and
      spectroscopic characterization, we further show that the Ostwald ripening rates
      of the catalysts and the porosity of the alumina support correlate with the
      lifetime and activity of the catalysts. Specifically, our results reveal that
      SWNT carpet growth is maximized by very low Ostwald ripening rates, mild
      subsurface diffusion rates, and high porosity, which is best achieved in the
      sputtered/Fe catalyst. These results not only emphasize the connection between
      catalytic activity and particle stability during growth, but guide current
      efforts aimed at rational design of catalysts for enhanced and controlled SWNT
      carpet growth.

PMID- 20131856
TI  - Graphene nanoribbons obtained by electrically unwrapping carbon nanotubes.
AB  - We describe a clean method of graphene nanoribbon (GNR) extraction from multiwall
      carbon nanotubes (MWNTs), performed in a high vacuum, nonchemical environment.
      Electrical current and nanomanipulation are used to unwrap a portion of the MWNT
      and thus produce a GNR of desired width and length. The unwrapping method allows
      GNRs to be concurrently characterized structurally via high-resolution
      transmission electron microscopy (TEM) and evaluated for electrical transport,
      including situations for which the GNR is severely mechanically flexed. High
      quality GNRs have exceptional current-carrying capacity, comparable to the
      exfoliated graphene.

PMID- 20131857
TI  - Enantioselective synthesis of alpha-quaternary amino acid derivatives by
      sequential enzymatic desymmetrization and Curtius rearrangement of alpha,alpha
      disubstituted malonate diesters.
AB  - A convenient and versatile enantioselective synthesis of biologically important
      alpha-quaternary amino acid derivatives was based on the sequential double
      alkylation or arylation of dimethyl malonate, followed by desymmetrization with
      porcine liver esterase (PLE) and Curtius rearrangement. The PLE-mediated
      hydrolysis of the prochiral dialkylated malonate diesters produced the
      corresponding chiral half-esters in high yield and with enantiomeric excesses of
      43% to >98%. Curtius rearrangement of the latter products, after trapping of the
      intermediate isocyanates with benzyl alcohol or amines, afforded the
      corresponding Cbz-protected amino esters or ureas. The absolute configurations of
      the major products in five examples were established by conversion to compounds
      with known specific rotations, or by X-ray crystallography of derivatives
      obtained with chiral amines of known configuration.

PMID- 20131858
TI  - 2-Pyridylnitrene and 3-pyridazylcarbene and their relationship via ring
      expansion, ring-opening, ring-contraction, and fragmentation.
AB  - Photolysis of triazolo[1,5-b]pyridazine 8 isolated in Ar matrix generates
      diazomethylpyridazines 9Z and 9E and diazopentenynes 11Z and 11E as detected by
      IR spectroscopy. ESR spectroscopy detected the 3-pydidazylcarbene 10 as well as
      pent-2-en-3-yn-1-ylidene 12 formed by loss of one and two molecules of N(2),
      respectively. Further photolysis caused rearrangement of the carbenes to 1,2
      pentadien-4-yne 13 and 3-ethynylcyclopropene 14. Flash vacuum thermolysis (FVT)
      of 8 at 400-500 degrees C with Ar matrix isolation of the products yielded 13,
      14, and 1,4-pentadiyne 15. At higher temperatures, glutacononitriles 27Z and 27E
      were formed as well together with minor amounts of 2- and 3-cyanopyrroles 28 and
      29. Tetrazolo[1,5-a]pyridine/2-azidopyridine 22T/22A yields 2-pyridylnitrene 19
      as well as the novel open-chain cyanodienylnitrene 23 and the ring-expanded 1,3
      diazacyclohepta-1,2,4,6-tetraene 21 on short wavelength photolysis. Nitrenes 19
      and 23 were detected by ESR spectroscopy, and cumulene 21 by IR and UV
      spectroscopy. FVT of 22T/22A also affords 2-pyridylnitrene 19 and
      diazacycloheptatetraene 21, as well as glutacononitriles 27Z,E and 2- and 3
      cyanopyrroles 28 and 29. Photolysis of 21 above 300 nm yields the novel
      spiroazirene 25, identified by its matrix IR spectrum. The reaction pathways
      connecting the four carbenes (10Z,E and 12Z,E) and three nitrenes (19, 23EZ, and
      23ZZ) in their open-shell singlet and triplet states are elucidated with the aid
      of theoretical calculations at DFT, CASSCF, and CASPT2 levels. Three possible
      mechanisms of ring-contraction in arylnitrenes are identified: (i) via ring
      opening to dienylnitrenes, (ii) concerted ring-contraction, and (iii) via
      spiroazirenes 25, whereby (i) is the energetically most favorable.

PMID- 20131859
TI  - Natural cyclodextrins as efficient boosters of the chemiluminescence of luminol
      and isoluminol: exploration of potential applications.
AB  - The chemiluminescent oxidation of luminol (LUM) and isoluminol (ISOL) is notably
      enhanced, both in intensity and duration, in the presence of natural
      cyclodextrins (alpha-, beta-, gamma-CD). The experiments have considered some of
      the most widespread applications of these compounds: the determination of metal
      cations and the revealing of bloodstains by oxidation with hydrogen peroxide in
      alkaline solution in the presence of Co(II), Fe(III), human hemoglobin, and
      blood, in order to explore potential applications. The largest enhancement in the
      emitted intensity occurs for the reaction of LUM with Co(II) in the presence of
      beta-CD. The use of the more soluble gamma-CD permits to expand the range of
      concentration and obtain more intense emission, although soluble derivatives of
      the beta-CD (methyl, hydroxypropyl-beta-CD, and a soluble cross-linked
      epichlorhydrin polymer) do not improve the chemiluminescence (CL) yield. In the
      case of hemoglobin and diluted human blood, the CDs aid in producing more light
      but only at high concentration of CDs, with a more lasting luminescence, up to
      three times longer. The changes in CL when glucose is used instead, much lower
      than with any of the CDs, imply that the cyclic structure of these
      oligosaccharides plays a key factor in the boosting of the emission. The results
      are explained in terms of the binding between the luminescent intermediate of the
      reaction, 3-aminophthalate (3-AP) and the CD, rather than to the luminescent
      reactant itself. The association constants obtained by steady-state fluorescence
      by assuming 1:1 stoichiometries reveal that the most stable association occurs
      between beta-CD and the intermediate, in accordance with the trend in the
      chemiluminescence. The topology of the complex deduced via ROESY experiments
      confirms a shallow inclusion of the double-charged intermediate by the primary
      rim of the CD, which accounts for the low stability of the complexes.

PMID- 20131860
TI  - Use of perfluorinated phosphines to provide thermomorphic anticancer complexes
      for heat-based tumor targeting.
AB  - A series of compounds of general formula [Ru(eta(6)-arene)(pta)(PR(3))Cl]BF(4)
      (arene = p-cymene or 4-phenyl-2-butanol; pta = 1,3,5-triaza-7
      phosphatricyclo[3.3.1.1]decane, PR(3) = PPh(2)(p-C(6)H(4)C(2)H(4)C(8)F(17)),
      PPh(p-C(6)H(4)C(2)H(4)C(8)F(17))(2), P(p-C(6)H(4)C(2)H(4)C(6)F(13))(3), PPh(3) or
      P(p-C(6)H(4)F)(3)) have been prepared and characterized by spectroscopic methods.
      The structure of [Ru(eta(6)-p-cymene)(pta)Cl(P(p-C(6)H(4)F)(3))]BF(4) has also
      been established in the solid state by X-ray crystallography. The cytotoxicities
      of the compounds were determined in the A2780 and A2780 cisplatin-resistant cell
      lines revealing that the fluorinated phosphines significantly increase
      antiproliferative activity relative to their bis-chloride precursors. Two of the
      complexes were found to be thermoresponsive, that is, showing poor water
      solubility at 37 degrees C and good solubility at 42 degrees C, the temperature
      of a heated tumor, providing a method of tumor targeting. Incubation at 42
      degrees C for 2 h resulted in improved cytotoxicities for two of the complexes.

PMID- 20131861
TI  - Insight into water oxidation by mononuclear polypyridyl Ru catalysts.
AB  - A family of compounds based on the mononuclear coordination complex
      [Ru(tpy)(bpy)(OH(2))](2+) (1b; tpy = 2,2':6',2''-terpyridine, bpy = 2,2'
      bipyridine) are shown to be competent catalysts in the Ce(IV)-driven oxidation of
      water in acidic media. The systematic installation of electron-withdrawing (e.g.,
      -Cl, -COOH) and -donating (e.g., -OMe) groups at various positions about the
      periphery of the polypyridyl framework offers insight into how electronic
      parameters affect the properties of water oxidation catalysts. It is observed, in
      general, that electron-withdrawing groups (EWGs) on the bpy ligands suppress
      catalytic activity (k(obs)) and enhance catalytic turnover numbers (TONs);
      conversely, the presence of electron-donating groups (EDGs) accelerate catalytic
      rates while decreasing catalyst stability. We found that 2,2'-bipyridine N,N'
      dioxide is produced when 1b is subject to excess Ce(IV) in acidic media, which
      suggests that dissociation of the bpy ligand is a source of catalyst deactivation
      and/or decomposition. Density functional theory (DFT) calculations corroborate
      these findings by showing that the Ru-N(bpy) bond trans to the O atom is weakened
      at higher oxidation levels while the other Ru-N bonds are affected to a lesser
      extent. We also show that the Ru-Cl bond is not robust in aqueous media, which
      has implications in studying the catalytic behavior of systems of this type.

PMID- 20131862
TI  - Electron spin resonance studies of the reorientational motion of Ni(mnt)2(-).
AB  - Electron spin resonance studies of the planar bis(maleonitriledithiolato)nickel
      complex ion, Ni(mnt)(2)(-), have been carried out from the motional narrowing
      region to the glassy limit in a series of ethers: 2-methyltetrahydrofuran (MTHF),
      diethylene glycol dimethyl ether (diglyme), triethylene glycol dimethyl ether
      (triglyme), and tetraethylene glycol dimethyl ether (tetraglyme). Analyses of the
      spectra show that Ni(mnt)(2)(-) is reorienting a factor of 3 faster about its
      long in-plane axis in all of these solvents; i.e., axially symmetric rotational
      diffusion produces agreement between the experimental and calculated line widths
      with D(parallel)/D(perpendicular) = 3.0 +/- 0.2; D(parallel) and D(perpendicular)
      are the diffusion constants for reorientation about the long in-plane (parallel)
      and perpendicular axes, respectively. The temperature dependence of the
      reorientational correlation time tau(2)(0) = (6D(perpendicular))(-1) determined
      from the widths is in agreement with the modified Stokes-Einstein-Debye model;
      the results indicate that Ni(mnt)(2)(-) has relatively strong (but not
      associative) interactions with the ethers. The experimental values of tau(2)(0)
      and the solvents' viscosities, self-diffusion constants, and dielectric
      relaxation times are compared and found to have a common temperature dependence.
      The ESR data also are compared with values of tau(solv), the correlation time
      obtained when a fluorescent probe is excited and its emission is monitored as the
      nonequilibrium solvent distribution relaxes. tau(solv) and tau(2)(0) are found to
      have a common temperature dependence in MTHF, tetraglyme, and two other solvents
      (ethyl alcohol and 1-butanol) in which Ni(mnt)(2)(-) has been studied. The
      factors determining these transport properties are discussed.

PMID- 20131863
TI  - Direct measure of strain and electronic structure in GaAs/GaP core-shell
      nanowires.
AB  - Highly strained GaAs/GaP nanowires of excellent optical quality were grown with
      50 nm diameter GaAs cores and 25 nm GaP shells. Photoluminescence from these
      nanowires is observed at energies dramatically shifted from the unstrained GaAs
      free exciton emission energy by 260 meV. Using Raman scattering, we show that it
      is possible to separately measure the degree of compressive and shear strain of
      the GaAs core and show that the Raman response of the GaP shell is consistent
      with tensile strain. The Raman and photoluminescence measurement are both on good
      agreement with 8 band k.p calculations. This result opens up new possibilities
      for engineering the electronic properties of the nanowires for optimal design of
      one-dimensional nanodevices by controlling the strain of the core and shell by
      varying the nanowire geometry.

PMID- 20131864
TI  - 1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as potent and selective
      norepinephrine reuptake inhibitors.
AB  - Efforts to identify new selective and potent norepinephrine reuptake inhibitors
      (NRIs) for multiple indications by structural modification of the previous 3
      (arylamino)-3-phenylpropan-2-olamine scaffold led to the discovery of a novel
      series of 1-(indolin-1-yl)-1-phenyl-3-propan-2-olamines (9). Investigation of the
      structure-activity relationships revealed that small alkyl substitution at the C3
      position of the indoline ring enhanced selectivity for the norepinephrine
      transporter (NET) over the serotonin transporter (SERT). Several compounds
      bearing a 3,3-dimethyl group on the indoline ring, 9k, 9o,p, and 9s,t, exhibited
      potent inhibition of NET (IC(50) = 2.7-6.5 nM) and excellent selectivity over
      both serotonin and dopamine transporters. The best example from this series, 9p,
      a potent and highly selective NRI, displayed oral efficacy in a telemetric rat
      model of ovariectomized-induced thermoregulatory dysfunction, a mouse p
      phenylquinone (PPQ) model of acute visceral pain, and a rat spinal nerve ligation
      (SNL) model of neuropathic pain.

PMID- 20131865
TI  - Laser ionization orthogonal time-of-flight mass spectrometry for simultaneous
      determination of nonmetallic elements in solids.
AB  - The simultaneous determination of nonmetallic elements in solid samples is
      difficult owing to their discrepant physical and chemical properties. We
      developed a high-irradiance laser ionization orthogonal time-of-flight mass
      spectrometry (LI-O-TOFMS) system and applied it for the determination of
      nonmetallic elements in solids. Helium was used as the buffer gas at 250 Pa in
      the source chamber; the laser irradiance was about 7 x 10(10) W/cm(2). A series
      of artificial standards containing B, C, N, O, F, Si, P, S, Cl, As, Br, Se, I,
      and Te were used. Explicit spectra were obtained with only a little interference
      from gas species and doubly charged matrix ions. Standardless semiquantitative
      analysis could be accomplished with a novel sampling methodology to obtain near
      uniform sensitivity coefficients for different elements. Limits of detection
      (LOD) at microgram per gram level and a dynamic range of 6 orders of magnitude
      were achieved for most nonmetallic elements.

PMID- 20131866
TI  - Structure and in vitro biological testing of water-based ferrofluids stabilized
      by monocarboxylic acids.
AB  - Water-based ferrofluids (magnetic fluids) with double-layer steric stabilization
      by short monocarboxylic acids (lauric and myristic acids) are considered to be a
      potential source of magnetic nanoparticles in brain cancer (glioblastoma)
      treatment. Structure characterization in the absence of an external magnetic
      field is performed, including transmission electron microscopy, magnetization
      analysis, and small-angle neutron scattering with contrast variation. It is shown
      that despite the good stability of the systems a significant part of the
      magnetite nanoparticles are in aggregates, whose inner structure depends on the
      stabilizer used. In particular, an incomplete coating of magnetite particles is
      concluded in the case of myristic acid stabilization. The ferrofluids keep their
      structure unchanged when added to the cancer cell medium. The intracellular
      accumulations of magnetite from the ferrofluids added to cancer cell cultures as
      well as its cytotoxicity with respect to human brain cells are investigated.

PMID- 20131867
TI  - Mass spectrometry-based GPCR proteomics: comprehensive characterization of the
      human cannabinoid 1 receptor.
AB  - The human cannabinoid 1 receptor (hCB1), a ubiquitous G protein-coupled receptor
      (GPCR), transmits cannabinergic signals that participate in diverse
      (patho)physiological processes. Pharmacotherapeutic hCB1 targeting is considered
      a tractable approach for treating such prevalent diseases as obesity, mood
      disorders, and drug addiction. The hydrophobic nature of the transmembrane
      helices of hCB1 presents a formidable difficulty to its direct structural
      analysis. Comprehensive experimental characterization of functional hCB1 by mass
      spectrometry (MS) is essential to the targeting of affinity probes that can be
      used to define directly hCB1 binding domains using a ligand-assisted experimental
      approach. Such information would greatly facilitate the rational design of hCB1
      selective agonists/antagonists with therapeutic potential. We report the first
      high-coverage MS analysis of the primary sequence of the functional hCB1
      receptor, one of the few such comprehensive MS-based analyses of any GPCR.
      Recombinant C-terminal hexa-histidine-tagged hCB1 (His6-hCB1) was expressed in
      cultured insect (Spodoptera frugiperda) cells, solubilized by a procedure devised
      to enhance receptor purity following metal-affinity chromatography, desalted by
      buffer exchange, and digested in solution with (chymo)trypsin. "Bottom-up" nanoLC
      MS/MS of the (chymo)tryptic digests afforded a degree of overall hCB1 coverage
      (>94%) thus far reported for only two other GPCRs. This MS-compatible procedure
      devised for His6-hCB1 sample preparation, incorporating in-solution
      (chymo)trypsin digestion in the presence of a low concentration of CYMAL-5
      detergent, may be applicable to the MS-based proteomic characterization of other
      GPCRs. This work should help enable future ligand-assisted structural
      characterization of hCB1 binding motifs at the amino-acid level using rationally
      designed and targeted covalent cannabinergic probes.

PMID- 20131868
TI  - Mesoporous silica microparticles enhance the cytotoxicity of anticancer platinum
      drugs.
AB  - We report on the endocytosis and the time-dependent enhanced cytotoxicity of
      anticancer platinum drugs when the drugs are combined with (or loaded into) one
      of the two most common types of mesoporous silica materials, MCM-41 or SBA-15.
      The anticancer drug cisplatin and its isomer transplatin, when loaded on MCM-41
      and SBA-15 microparticles, were less cytotoxic to leukemia cells than the drugs
      alone after 12 h exposure. However, the drug-loaded microparticles exhibited
      unprecedented enhanced cytotoxicity to the cancerous cells after 24 h of
      exposure. This cytotoxicity of the drug-loaded microparticles was even higher
      than of the pure drugs in solutions, suggesting that mesoporous silica
      microparticles loaded with cisplatin or transplatin enabled a localized
      intracellular release of the platinum compounds and possibly also facilitated the
      drug's hydrolysis, enhancing the desired cytotoxic effect.

PMID- 20131869
TI  - The structure of p85ni in class IA phosphoinositide 3-kinase exhibits interdomain
      disorder.
AB  - Regulation of the class IA PI 3-kinase involves inhibition and stabilization of
      the catalytic subunit (p110) by the regulatory subunit (p85). Regulation is
      achieved by two major contacts: a stable interface involving the adapter-binding
      domain (ABD) of p110 and the inter-SH2 (iSH2) domain of p85 and a regulatory
      interaction between the N-terminal SH2 (nSH2) domain of p85 and the helical
      domain of p110. In the present study, we have examined the relative orientation
      of the nSH2 and iSH2 of p85alpha using site-directed spin labeling and pulsed
      EPR. Surprisingly, both distance measurements and distance distributions suggest
      that the nSH2 domain is highly disordered relative to the iSH2 domain. Molecular
      modeling based on EPR distance restraints suggests that the nSH2 domain moves in
      a hinge-like manner, sampling a torus space around the proximal end of the iSH2
      domain. These data have important implications for the mechanism by which
      p85/p110 dimers are regulated by phosphopeptides.

PMID- 20131870
TI  - Atomic layer deposition of dielectric overlayers for enhancing the optical
      properties and chemical stability of plasmonic nanoholes.
AB  - Fabricating plasmonic nanostructures with robust optical and chemical properties
      remains a challenging task, especially with silver, which has superior optical
      properties but poor environmental stability. In this work, conformal atomic layer
      deposition (ALD) of thin alumina overlayers is used to precisely tune the optical
      transmission properties of periodic nanohole arrays made in gold and silver
      films. Experiments and computer simulations confirm that ALD overlayers with
      optimized thicknesses tune and enhance the transmitted intensity due to
      refractive index matching effects and by modifying the dielectric properties of
      each nanohole. Furthermore, encapsulating silver nanohole arrays with thin
      alumina overlayers protects the patterned surfaces against unwanted oxidation and
      contamination. The ability to precisely tune the optical properties while
      simultaneously providing robust chemical stability can benefit a broad range of
      applications, including biosensing and fluorescence imaging.

PMID- 20131871
TI  - Reaction kinetics studied using diffusion-ordered spectroscopy and multiway
      chemometrics.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is frequently used in the
      monitoring of reaction kinetics, due to its nondestructive nature and to the
      wealth of chemical information that can be obtained. However, when spectra of
      different mixture components overlap, as is common, the information available is
      greatly reduced, sometimes to the point where the identification of individual
      chemical species is not possible. In such cases, the resolution of component
      spectra and their concentration timecourses can be greatly improved by recording
      DOSY (diffusion-ordered spectroscopy) data for each time point during the
      reaction. Adding this additional degree of freedom to the experimental data,
      allowing the signals of different species to be distinguished through their
      different rates of diffusion, makes the data trilinear and, therefore,
      susceptible to analysis by powerful multiway (here, more specifically
      multilinear) model-free decomposition methods such as PARAFAC (parallel factor
      analysis). This approach is shown to produce high quality data even for species
      with near-degenerate spectra. Another important limitation of NMR is its
      inherently low sensitivity. Here, we show that the combination of DOSY and
      PARAFAC is surprisingly robust with respect to input data with low signal-to
      noise ratio. High quality component spectra and kinetic profiles are obtained
      from a data set in which the signal-to-noise ratios of the reaction components in
      the spectra for individual time points are below the detection level.

PMID- 20131872
TI  - Blind separation of analytes in nuclear magnetic resonance spectroscopy and mass
      spectrometry: sparseness-based robust multicomponent analysis.
AB  - Metabolic profiling of biological samples involves nuclear magnetic resonance
      (NMR) spectroscopy and mass spectrometry coupled with powerful statistical tools
      for complex data analysis. Here, we report a robust, sparseness-based method for
      the blind separation of analytes from mixtures recorded in spectroscopic and
      spectrometric measurements. The advantage of the proposed method in comparison to
      alternative blind decomposition schemes is that it is capable of estimating the
      number of analytes, their concentrations, and the analytes themselves from
      available mixtures only. The number of analytes can be less than, equal to, or
      greater than the number of mixtures. The method is exemplified on blind
      extraction of four analytes from three mixtures in 2D NMR spectroscopy and five
      analytes from two mixtures in mass spectrometry. The proposed methodology is of
      widespread significance for natural products research and the field of metabolic
      studies, whereupon mixtures represent samples isolated from biological fluids or
      tissue extracts.

PMID- 20131873
TI  - Development of a point of care lateral flow device for measuring human plasma
      fibrinogen.
AB  - Fibrinogen is a major cardiovascular disease risk factor and is an independent
      predictor of coronary heart disease and stroke. Normal reference levels are
      approximately 2 to 4 g/L. Elevated levels are associated with the occurrence of
      cardiovascular disease-related events. The risk of increased bleeding in major
      surgery is inversely correlated with fibrinogen concentrations for concentrations
      below the upper limit of the reference interval, i.e., <4 g/L. Determination of
      the clottable fibrinogen concentration in plasma is, thus, important for the
      investigation of coagulation disturbances in patients. A novel assay for
      monitoring plasma fibrinogen content has been developed on the basis of a simple,
      single use lateral flow microfluidic device. A 15 microL plasma sample is applied
      to and travels along the microstructured device where it comes into contact with
      a thrombin reagent. This induces conversion of the soluble fibrinogen to
      insoluble fibrin and brings about clot formation. Lateral sample flow is arrested
      as a result of clotting, and the distance along the device at which this occurs
      has been shown to be dependent on the fibrinogen concentration. The test range
      was from 1 to 7 g/L of fibrinogen in undiluted patient plasma, and a result could
      be obtained within 5 min.

PMID- 20131874
TI  - Structure, photophysical and electrochemical properties, biomolecular
      interactions, and intracellular uptake of luminescent cyclometalated iridium(III)
      dipyridoquinoxaline complexes.
AB  - A series of luminescent cyclometalated iridium(III) dipyridoquinoxaline complexes
      [Ir(N--C)(2)(N--N)](PF(6)) (HN--C = 1-phenylpyrazole, Hppz, N--N = dipyrido[3,2
      f:2',3'-h]quinoxaline, dpq (1a), 2-(n-butylamido)dipyrido[3,2-f:2',3'
      h]quinoxaline, dpqa (1b); HN--C = 7,8-benzoquinoline, Hbzq, N--N = dpq (2a), dpqa
      (2b); HN--C = 2-phenylquinoline, Hpq, N--N = dpq (3a), dpqa (3b)) has been
      synthesized and characterized. Cyclic voltammetric studies revealed a reversible
      or quasi-reversible iridium(IV/III) oxidation couple at about +1.13 to +1.32 V
      and a reversible diimine reduction couple at about -1.10 to -1.29 V versus SCE.
      Upon photoexcitation, all the complexes displayed intense and long-lived green to
      orange triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi*(dpq or
      dpqa)) emission in aprotic organic solvents at room temperature and in low
      temperature glass. In aqueous solution, these complexes were only weakly emissive
      or even non-emissive. The lipophilicity of all the complexes has been determined
      by reversed-phase HPLC. The cytotoxicity of these iridium(III) complexes toward
      the human cervix epithelioid carcinoma (HeLa) and Madin-Darby canine kidney
      (MDCK) cell lines has been evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5
      diphenyltetrazolium bromide (MTT) assay. The cellular uptake of the complexes by
      MDCK cells has been examined by laser-scanning confocal microscopy. Most
      importantly, apparent nucleolar staining was observed after the cells were
      treated by the complexes. The interactions of these complexes with proteins, DNA,
      and RNA have also been studied by emission titrations and SDS-PAGE gel staining.
      The results revealed that the complexes bound to the hydrophobic pockets of
      proteins, intercalated into the base-pairs of double-stranded DNA, but did not
      appear to interact with RNA.

PMID- 20131875
TI  - A 13-Oxo-9,10-epoxytridecenoate phospholipid analogue of the genotoxic 4,5-epoxy
      2E-decenal: detection in vivo, chemical synthesis, and adduction with DNA.
AB  - Often guided by analogy with nonphospholipid products from oxidative cleavage of
      polyunsaturated fatty acids, we previously identified a variety of biologically
      active oxidatively truncated phospholipids. Previously, 4,5-epoxy-2(E)-decenal
      (4,5-EDE) was found to be produced by oxidative cleavage of 13-(S)-hydroperoxy
      9,11-(Z,E)-octadeca-dienoic acid (13-HPODE). 4,5-EDE reacts with deoxy-adenosine
      (dAdo) and deoxy-guanosine (dGuo) to form mutagenic etheno derivatives. We
      hypothesized that a functionally similar and potentially mutagenic compound, that
      is, 13-oxo-9,10-epoxytridecenoic acid (OETA), would be generated from 9-HPODE
      through an analogous fragmentation. We expected that an ester of 2
      lysophosphatidylcoline (PC), OETA-PC, would be produced by oxidative cleavage of
      9-HPODE-PC in biological membranes. An efficient, unambiguous total synthesis of
      trans-OETA-PC was first executed to provide a standard that could facilitate the
      identification of this phospholipid epoxyalkenal that was shown to be produced
      during oxidation of the linoleic acid ester of 2-lysoPC. Finally, trans-OETA-PC
      was detected in a lipid extract from rat retina. The identity of the naturally
      occurring oxidatively truncated phospholipid was further confirmed by
      derivatization with methoxylamine that produced characteristic mono and bis
      adducts. The average amount of trans-OETA-PC in rat retina, 0.33 pmol, is
      relatively low as compared to other oxidatively truncated PCs, for example, the 4
      hydroxy-7-oxohept-5-enoic acid PC ester (2.5 pmol) or the 4-keto-7-oxohept-5
      enoic acid PC ester (1.7 pmol), derived from the docosahexaenoic acid ester of 2
      lysoPC. This, most likely, is because docosahexaenoate PCs are particularly
      abundant in the retina as compared to the linoleate PC ester precursor of OETA
      PC. As predicted by analogy with 4,5-EDE, OETA-PC reacts with dAdo and dGuo, as
      well as with DNA, to form mutagenic etheno adducts.

PMID- 20131877
TI  - Toward white light emission through efficient two-step energy transfer in hybrid
      nanofibers.
AB  - Nanosized zeolite L crystals containing about 550 strongly luminescent acceptor
      molecules have been modified by grafting a conjugated oligomer on their external
      surface. The 25 nm sized crystals have consequently been embedded in polymeric
      nanofibers obtained by electrospinning. The fluorescent molecule grafted on the
      external surface allows addressing the guests in the zeolite nanochannels through
      an efficient two-step energy transfer from the polymer nanofiber. The so obtained
      hybrid nanofibers exhibit intense emissions from the three fundamental colors
      using a single excitation wavelength. The molecule grafted on the external
      surface of the nanocrystal also induces a higher compatibility of the hybrid
      organic/inorganic nanomaterials in the conjugated polymer and therefore high
      concentrations of zeolites embedded in the nanofibers are obtained. Playing on
      this concentration, the emission of the nanofiber can be tuned and eventually be
      used for fabricating white-light emitting nanofibers. This hybrid nanomaterial
      opens new perspectives for low-cost nano organic light emitting diodes
      fabrication with considerable impact on the lighting and display technologies.

PMID- 20131876
TI  - A quantitative assessment of nanoparticle-ligand distributions: implications for
      targeted drug and imaging delivery in dendrimer conjugates.
AB  - Functional nanoparticles often contain ligands including targeting molecules,
      fluorophores, and/or active moieties such as drugs. Characterizing the number of
      these ligands bound to each particle and the distribution of nanoparticle-ligand
      species is important for understanding the nanomaterial's function. In this
      study, the amide coupling methods commonly used to conjugate ligands to
      poly(amidoamine) (PAMAM) dendrimers were examined. A skewed Poisson distribution
      was observed and quantified using HPLC for two sets of dendrimer-ligand samples
      prepared using the amine-terminated form of the PAMAM dendrimer and a partially
      acetylated form of the PAMAM dendrimer that has been used for targeted in vivo
      drug delivery. The prepared samples had an average number of ligands per
      dendrimer ranging from 0.4 to 13. Distributions identified by HPLC are in
      excellent agreement with the mean ligand/dendrimer ratio, measured by (1)H NMR,
      gel permeation chromatography (GPC), and potentiometric titration. These results
      provide insight into the heterogeneity of distributions that are obtained for
      many classes of nanomaterials to which ligands are conjugated and belie the use
      of simple cartoon models that present the "average" number of ligands bound as a
      physically meaningful representation for the material.

PMID- 20131878
TI  - Unsymmetrical triangular Schiff base macrocycles with cone conformations.
AB  - Two new unsymmetrical Schiff base macrocycles with isosceles triangle shapes have
      been prepared. The macrocycles adopt cone-shaped conformations that rapidly
      interconvert at high temperature. Dynamic NMR studies show that the macrocycle
      that is tautomerized to the keto-enamine isomer is slower to flip than is the one
      in the enol-imine state. These macrocycles are good hosts for binding organic
      cations in their interiors.

PMID- 20131879
TI  - [4 + 2] Cycloaddition reactions catalyzed by a chiral oxazaborolidinium cation.
      Reaction rates and diastereo-, regio-, and enantioselectivity depend on whether
      both bonds are formed simultaneously.
AB  - The reaction rates and products in enantioselective Diels-Alder reactions with a
      range of dienophiles correlate with the expected degree of concertedness of bond
      formation in the transition state.

PMID- 20131880
TI  - Selective tethering of ligands and proteins to a microfluidically patterned
      electroactive fluid lipid bilayer array.
AB  - We report a new, quantitative methodology to pattern and present ligands from
      planar, supported, fluid lipid bilayers. By combining microfluidic lithography
      (microFL) with an electroactive, chemoselective interfacial reaction strategy, a
      number of ligands as well as protein concanavalin A were immobilized in lipid
      microarrays. Electroactive vesicles were generated after the spontaneous
      insertion of hydroquinone-tethered alkane (H(2)Q) into egg palmitoyl-oleoyl
      phosphatidylcholine (egg-POPC), followed by subsequent fusion to a siloxane
      terminated self-assembled monolayer (SAM) on gold. An advantage of the H(2)Q
      system is that it can be electrochemically oxidized to the corresponding quinone
      (Q), followed by rapid chemoselective conjugation with oxyamine-functionalized
      (RONH(2)) ligands. The oxime product is also electroactive, and the reaction can
      be monitored and the amount of ligand bound can be quantified by
      electrochemistry. The bilayers were characterized by electrochemistry,
      fluorescence microscopy, and ellipsometry and were determined to be fluid by
      fluorescence recovery after photobleaching (FRAP). This strategy provides a
      synergistic method to pattern and present a number of ligands or biomolecules
      from the bilayer surface for the evaluation of enzyme or protein binding to
      biomembranes.

PMID- 20131881
TI  - Fabrication of superhydrophobic surfaces with high and low adhesion inspired from
      rose petal.
AB  - Certain rose petals are known to be superhydrophobic with high adhesion. There
      also exist rose petals which are superhydrophobic with low adhesion similar to
      lotus leaf. The purpose of this study is to characterize systematically the
      superhydrophobic rose petal with high and low adhesion surfaces and understand
      the mechanism for adhesion characteristics. Based on these, artificial
      superhydrophobic surfaces with high and low adhesion are fabricated using a two
      step molding process and wax evaporation method. It is shown that the pitch
      values of microstructures and density of nanostructures play an important role in
      real rose petals and artificial surfaces to control their adhesion properties.

PMID- 20131882
TI  - Zn- and Mg-doped hydroxyapatite nanoparticles for controlled release of protein.
AB  - Bovine serum albumin (BSA) protein incorporated with hydroxyapatite (HA)
      nanoparticles (NPs) were synthesized by an in situ precipitation process. 2 mol %
      Zn(2+) and Mg(2+) were used as dopants to synthesize Zn(2+)/Mg(2+)-doped HA-BSA
      NPs. In our study we used BSA as a model protein. The amount of BSA uptake by
      doped and undoped HA NPs and subsequent release of BSA from NPs were
      investigated. Zn-doped HA NPs showed the highest amount of BSA uptake, whereas
      the amount of BSA loaded in undoped HA NPs was the lowest. A two-stage BSA
      release profile from doped and undoped HA NPs was observed in phosphate buffer
      solution (PBS) at pH 7.2 +/- 0.2. The initial burst release was due to the
      desorption of BSA from the HA surface. The later stage of slow release was
      controlled by the dissolution of BSA incorporated HA NPs. The BSA release rate
      from Zn-doped HA NPs was found to be the highest, whereas undoped HA NPs released
      BSA at the slowest rate. Our study showed that the protein release rate from HA
      NPs can be controlled by the addition of suitable dopants, and doped HA-based NP
      systems can be used in bone growth factor and drug release study.

PMID- 20131883
TI  - Dominant conformation of valsartan in sodium dodecyl sulfate micelle environment.
AB  - The interaction of valsartan (VST), a novel antihypertensive drug, with sodium
      dodecyl sulfate (SDS) micelles has been investigated using Nuclear Magnetic
      Resonance (NMR) spectroscopy and Molecular Dynamics (MD) simulation. VST has two
      conformations in solution, exchanging slowly on the NMR time scale via the
      trans/cis (conformer A/B) isomerization of the amide bond. It is suggested that
      drugs in the sartan class incorporate and diffuse into biological membranes
      before they interact with AT(1) receptors. SDS is used to mimic the membrane
      environment to characterize two VST conformers. (1)H NMR chemical shift analysis,
      proton relaxation rates, and self-diffusion coefficient measurements suggest that
      conformer A has a higher binding affinity to SDS and is the dominant conformer
      distributed in the SDS micelles. The location of VST in the micelles is
      determined by NOE measurements and by the MD simulation, showing that the butyl
      chain and biphenyl groups of VST interact with the alkyl group of SDS through
      hydrophobic interactions. Preferable binding free energy is found for conformer A
      by the MD simulation, which demonstrates that the relatively concentrated
      hydrophobic surface of conformer A is responsible for its higher affinity to the
      micelles. Our results are in good agreement with a recent simulation of VST bound
      onto the AT(1) receptor by Potamitis et. al (J. Chem. Inf. Model. 2009) who
      demonstrate that conformer A (trans conformation in their definition) is the one
      binding to the receptor. The results presented in our study suggest that the
      biological membrane plays an essential role in stabilization of the active state
      of VST. Thus, understanding the interactions between the sartan drugs and the
      membrane environment should facilitate the studies of the functional mechanism of
      these compounds with their receptor and provide insight on the development of new
      approaches for drug discovery.

PMID- 20131884
TI  - Spatially resolved quantification of E-cadherin on target hES cells.
AB  - The local expression and distribution pattern of protein on a cell play essential
      roles in signal transduction within a cell or between cells. Here we report on
      the development of a spatially resolved quantification method, which was applied
      in the study of E-cadherin local expression in identified undifferentiated and
      differentiated human embryonic stem (hES) cells in their native cellular
      environment. This was achieved by a novel immunofluorescence assisted affinity
      mapping (IF-AM) method, in which immunofluorescence provides the guidance to
      locate a desired type of cell in a cell community for performing affinity mapping
      to quantify the local protein density. The results unveiled the crucial role of E
      cadherin in mediating hES cell proliferation and differentiation: the expression
      of E-cadherin is markedly higher on undifferentiated cells, and the growth of hES
      cells in unique colonies is contingent on the homogeneous distribution of E
      cadherin. Due to the ability of directly assessing individual proteins of a cell,
      the IF-AM method is shown to be a sensitive tool for resolving subtle differences
      in the local expression of membrane proteins even at low abundance.

PMID- 20131885
TI  - Balancing simulation accuracy and efficiency with the Amber united atom force
      field.
AB  - We have analyzed the quality of a recently proposed Amber united-atom model and
      its overall efficiency in ab initio folding and thermodynamic sampling of two
      stable beta-hairpins. It is found that the mean backbone structures are quite
      consistent between the simulations in the united-atom and its corresponding all
      atom models in Amber. More importantly, the simulated beta turns are also
      consistent between the two models. Finally, the chemical shifts on H alpha are
      highly consistent between simulations in the two models, although the simulated
      chemical shifts are lower than experiment, indicating less structured peptides,
      probably due to the omission of the hydrophobic term in the simulations. More
      interestingly, the stabilities of both beta-hairpins at room temperature are
      similar to those derived from the NMR measurement, whether the united-atom or the
      all-atom model is used. Detailed analysis shows high percentages of backbone
      torsion angles within the beta region and high percentages of native contacts.
      Given the reasonable quality of the united-atom model with respect to
      experimental data, we have further studied the simulation efficiency of the
      united-atom model over the all-atom model. Our data shows that the united-atom
      model is a factor of 6-8 faster than the all-atom model as measured with the ab
      initio first pass folding time for the two tested beta-hairpins. Detailed
      structural analysis shows that all ab initio folded trajectories enter the native
      basin, whether the united-atom model or the all-atom model is used. Finally, we
      have also studied the simulation efficiency of the united-atom model as measured
      in terms of how fast thermodynamic convergence can be achieved. It is apparent
      that the united-atom simulations reach convergence faster than the all-atom
      simulations with respect to both mean potential energies and mean native
      contacts. These findings show that the efficiency of the united-atom model is
      clearly beyond the per-step dynamics simulation of about 2 over the all-atom
      model. Thus, reasonable reduction of a protein model can be achieved with
      improved sampling efficiency while still preserving a high level of accuracy for
      applications in both ab initio folding and thermodynamic sampling. This study
      motivates us to develop more simplified protein models with sufficient
      consistency with the all-atom models for enhanced conformational sampling.

PMID- 20131887
TI  - Kinetics of the R + NO2 reactions (R = i-C3H7, n-C3H7, s-C4H9, and t-C4H9) in the
      temperature range 201-489 K.
AB  - The bimolecular rate coefficients of four alkyl radical reactions with NO(2) have
      been measured in direct time-resolved experiments. Reactions were studied under
      pseudo-first-order conditions in a temperature-controlled tubular flow reactor
      coupled to a laser photolysis/photoionization mass spectrometer (LP-PIMS). The
      measured reaction rate coefficients are independent of helium bath gas pressure
      within the experimental ranges covered and exhibit negative temperature
      dependence. For i-C(3)H(7) + NO(2) and t-C(4)H(9) + NO(2) reactions, the
      dependence of ordinate (logarithm of reaction rate coefficients) on abscissa (1/T
      or log(T)) was nonlinear. The obtained results (in cm(3) s(-1)) can be expressed
      by the following equations: k(n-C(3)H(7) + NO(2)) = ((4.34 +/- 0.08) x 10(-11))
      (T/300 K)(-0.14+/-0.08) (203-473 K, 1-7 Torr), k(i-C(3)H(7) + NO(2)) = ((3.66 +/-
      2.54) x 10(-12)) exp(656 +/- 201 K/T)(T/300 K)(1.26+/-0.68) (220-489 K, 1-11
      Torr), k(s-C(4)H(9) + NO(2)) = ((4.99 +/- 0.16) x 10(-11))(T/300 K)(-1.74+/-0.12)
      (241-485 K, 2 - 12 Torr) and k(t-C(4)H(9) + NO(2)) = ((8.64 +/- 4.61) x 10(-12))
      exp(413 +/- 154 K/T)(T/300 K)(0.51+/-0.55) (201-480 K, 2-11 Torr), where the
      uncertainties shown refer only to the 1 standard deviations obtained from the
      fitting procedure. The estimated overall uncertainty in the determined
      bimolecular rate coefficients is about +/-20%.

PMID- 20131888
TI  - Chaotic dynamics and the recurrence spectra of the Rydberg hydrogen atom near a
      dielectric surface.
AB  - The classical electronic motion of the Rydberg hydrogen atom near a dielectric
      surface has been studied by using the Poincare surfaces of section method and the
      closed orbit theory. The structure and evolution of the phase space as a function
      of the scaled energy is explored extensively by means of the Poincare surfaces of
      section. The results suggest that when the scaled energy is less than the
      critical energy epsilon(s), the whole phase space structure is regular. However,
      when the energy is larger than epsilon(s), chaotic motions appear. The recurrence
      spectra of this system have also been calculated. The results show that, for a
      given scaled energy larger than the critical energy epsilon(s), when the
      dielectric constant alpha is small, the influence of the dielectric surface can
      be neglected and the number of closed orbits is very small. With the increase of
      the dielectric constant alpha, the effect of the dielectric surface becomes
      significant, the number of closed orbits increases, and there are more peaks in
      the recurrence spectra. When alpha = 1.0, the recurrence spectra approach the
      case of the Rydberg hydrogen atom near a metallic surface. This study provides a
      new method to explore the dynamic behavior of the Rydberg atom interacting with a
      dielectric surface.

PMID- 20131889
TI  - Surface morphology and phase transitions in mixed NaCl/MgSO4 aerosol particles.
AB  - Probe molecule spectroscopy characterizes the surface environment of mixed
      NaCl/MgSO(4) (0.01-50 wt % MgSO(4)) aerosol particles as a model for marine
      aerosol. Two complementary measurements, the probe's excited state spectroscopy
      and photoionization efficiency, measure the electronic properties of the particle
      surface and monitor phase changes that are driven by changes in relative humidity
      (RH). The results illustrate that over a wide range of composition, these
      particles have a layered structure with NaCl in the core and primarily hydrated
      MgSO(4) at the surface. Modeling the spectroscopic data reveals that the surface
      layer is not a uniform shell and that the coumarin 314 probe molecules partition
      selectively to the MgSO(4) domains. The surface layer has a pi* value of 1.7,
      indicative of a very high interfacial polarity. In cases where MgSO(4) is a minor
      component (< or = 10 wt %), the NaCl component crystallizes at 44% RH, consistent
      with the single salt NaCl result. Deliquescence-mode experiments with these
      particles show that the MgSO(4) component forms a solution at 42% RH, prior to
      the full deliquescence of the particle. For mixed particles with 50 wt % MgSO(4),
      the crystallization of NaCl occurs at 35% RH, and the predeliquescence of MgSO(4)
      occurs at 38% RH owing to the contribution of MgCl(2) in the surface layer. A
      model surfactant, SDS, slightly lowers the RH of the NaCl formation to
      approximately 42% and leads to the formation of a thin soap film that persists to
      low values of RH.

PMID- 20131890
TI  - Total synthesis of 10-isocyano-4-cadinene and determination of its absolute
      configuration.
AB  - The first enantioselective total synthesis of 10-isocyano-4-cadinene, a marine
      sesquiterpene isolated from nudibranchs of the family Phyllidiidae, was achieved.
      The cadinene is expected to be a novel nontoxic antifouling agent. In the
      synthesis, an intermolecular Diels-Alder reaction and a SmI(2)-induced Barbier
      type reaction were employed as key steps. The absolute configuration of 10
      isocyano-4-cadinene was determined to be (1S, 6S, 7R, 10S) on the basis of the
      total synthesis. Antifouling activities against Balanus amphitrite with both
      enantiomers of 10-isocyano-4-cadinene were also evaluated.

PMID- 20131891
TI  - Formation and superlattice of long-range-ordered self-assembled monolayers of
      pentafluorobenzenethiols on Au(111).
AB  - The formation and surface structure of pentafluorobenzenethiol (PFBT) self
      assembled monolayers (SAMs) on Au(111) formed under various experimental
      conditions were examined by means of scanning tunneling microscopy (STM).
      Although it is well known that PFBT molecules on metal surfaces do not form
      ordered SAMs, we clearly revealed for the first time that the adsorption of PFBT
      on Au(111) at 75 degrees C for 2 h yields long-range, well-ordered self-assembled
      monolayers having a (2 x 5 square root(13))R30 degrees superlattice. Our results
      will provide new insight into controlling the structural order of PFBT SAMs,
      which will be very useful in precisely tailoring the interface properties of
      metal surfaces in electronic devices.

PMID- 20131892
TI  - Applying AFM-based nanofabrication for measuring the thickness of nanopatterns:
      the role of head groups in the vertical self-assembly of omega-functionalized n
      alkanethiols.
AB  - Molecules of n-alkanethiols with methyl head groups typically form well-ordered
      monolayers during solution self-assembly for a wide range of experimental
      conditions. However, we have consistently observed that, for either carboxylic
      acid or thiol-terminated n-alkanethiols, under certain conditions nanografted
      patterns are generated with a thickness corresponding precisely to a double
      layer. To investigate the role of head groups for solution self-assembly,
      designed patterns of omega-functionalized n-alkanethiols were nanografted with
      systematic changes in concentration. Nanografting is an in situ approach for
      writing patterns of thiolated molecules on gold surfaces by scanning with an AFM
      tip under high force, accomplished in dilute solutions of desired ink molecules.
      As the tip is scanned across the surface of a self-assembled monolayer under
      force, the matrix molecules are displaced from the surface and are immediately
      replaced with fresh molecules from solution to generate nanopatterns. In this
      report, side-by-side comparison of nanografted patterns is achieved for different
      matrix molecules using AFM images. The chain length and head groups (i.e.,
      carboxyl, hydroxyl, methyl, thiol) were varied for the nanopatterns and matrix
      monolayers. Interactions such as head-to-head dimerization affect the vertical
      self-assembly of omega-functionalized n-alkanethiol molecules within nanografted
      patterns. At certain threshold concentrations, double layers were observed to
      form when nanografting with head groups of carboxylic acid and dithiols, whereas
      single layers were generated exclusively for nanografted patterns with methyl and
      hydroxyl groups, regardless of changes in concentration.

PMID- 20131893
TI  - Generation of monodisperse silk microspheres prepared with microfluidics.
AB  - Monodisperse microspheres of reconstituted silkworm cocoon silk were produced
      using a glass capillary-based microfluidic system and by identifying an
      appropriate solvent/nonsolvent fluid system. The microspheres can be produced to
      a range of different diameters depending on the system flow rates and have a
      nearly homogeneous size distribution. The silk microspheres exhibit a unique core
      -shell architecture and have a largely beta-sheet structure, as measured by
      infrared spectroscopy. Mechanical characterization was performed with AFM
      nanoindentation and indicates that the microspheres are unexpectedly soft for a
      silk material. Because silk is well established as biocompatible and
      biodegradable, we anticipate that these silk microspheres could have particular
      utility in drug delivery and controlled release.

PMID- 20131894
TI  - Design of double stimuli-responsive polyelectrolyte microcontainers for protein
      soft encapsulation.
AB  - We have designed new double stimuli-responsive polyelectrolyte microcapsules to
      be useable under physiological conditions to handle biomacromolecules while
      avoiding the risk of denaturation. They are made of poly(4-vinylpyridine
      hydrochloride) (PVP) and poly(sodium styrene sulfonate) (PSS). The
      microcontainers are sensitive to temperature variation, as they irreversibly
      shrink under heating. In addition, the capsules reversibly swell at pH > 6,
      making it possible to encapsulate human serum proteins by diffusion through the
      polymer membrane. Encapsulation efficiency is quantified by fluorescence
      techniques.

PMID- 20131895
TI  - Interplay between theory and experiment: computational organometallic and
      transition metal chemistry.
AB  - Computational and theoretical chemistry provide fundamental insights into the
      structures, properties, and reactivities of molecules. As a result, theoretical
      calculations have become indispensable in various fields of chemical research and
      development. In this Account, we present our research in the area of
      computational transition metal chemistry, using examples to illustrate how theory
      impacts our understanding of experimental results and how close collaboration
      between theoreticians and experimental chemists can be mutually beneficial. We
      begin by examining the use of computational chemistry to elucidate the details of
      some unusual chemical bonds. We consider the three-center, two-electron bonding
      in titanocene sigma-borane complexes and the five-center, four-electron bonding
      in a rhodium-bismuth complex. The bonding in metallabenzene complexes is also
      examined. In each case, theoretical calculations provide particular insight into
      the electronic structure of the chemical bonds. We then give an example of how
      theoretical calculations aided the structural determination of a kappa(2)-N,N
      chelate ruthenium complex formed upon heating an intermediate benzonitrile
      coordinated complex. An initial X-ray diffraction structure proposed on the basis
      of a reasonable mechanism appeared to fit well, with an apparently acceptable R
      value of 0.0478. But when DFT calculations were applied, the optimized geometry
      differed significantly from the experimental data. By combining experimental and
      theoretical outlooks, we posited a new structure. Remarkably, a re-refining of
      the X-ray diffraction data based on the new structure resulted in a slightly
      lower R value of 0.0453. We further examine the use of computational chemistry in
      providing new insight into C-H bond activation mechanisms and in understanding
      the reactivity properties of nucleophilic boryl ligands, addressing experimental
      difficulties with calculations and vice versa. Finally, we consider the impact of
      theoretical insights in three very specific experimental studies of chemical
      reactions, illustrating how theoretical results prompt further experimental
      studies: (i) diboration of aldehydes catalyzed by copper(I) boryl complexes, (ii)
      ruthenium-catalyzed C-H amination of arylazides, and (iii) zinc reduction of a
      vinylcarbyne complex. The concepts and examples presented here are intended for
      nonspecialists, particularly experimentalists. Together, they illustrate some of
      the achievements that are possible with a fruitful union of experiment and
      theory.

PMID- 20131896
TI  - Excited states of fluorescent proteins, mKO and DsRed: chromophore-protein
      electrostatic interaction behind the color variations.
AB  - The emitting states of green fluorescent protein (GFP), monomeric Kusabira orange
      (mKO), and Discosoma red (DsRed) were studied using QM/MM and SAC-CI methods. By
      comparing the electronic structures among the green-, orange-, and red-emitting
      states as well as their electrostatic and quantum mechanical interactions within
      the protein cavity, the basic mechanisms for determining emission colors have
      been clarified. We found that the orange and red emissions of mKO and DsRed,
      respectively, result from cancellation between two effects, the pi skeleton
      extension (red shift) and protein electrostatic potential (blue shift). The
      extension of the pi skeleton enhances the intramolecular charge-transfer
      character of the transition, which makes the fluorescence energy more sensitive
      to the protein's electrostatic potential. On the basis of this mechanism, we
      predicted amino acid mutations that could red shift the emission energy of DsRed.
      A novel single amino acid mutation, which was examined computationally, reduced
      the DsRed emission energy from 2.14 (579 nm) to 1.95 eV (636 nm), which is
      approaching near-infrared fluorescence.

PMID- 20131897
TI  - Quantification of water solubilized CdSe/ZnS quantum dots in Daphnia magna.
AB  - The relative transparency of Daphnia magna (daphnia) and the unique optical
      properties of quantum dots (QDs) were paired to study the accumulation potential
      and surface coating effects on uptake of amphiphilic polymer coated CdSe/ZnS QDs.
      Fluorescence confocal laser scanning microscopy was used to visualize and
      spectrally distinguish QDs from competing autofluorescent signals arising from
      the daphnia themselves and their food sources. QDs were found to accumulate
      within the digestive tracts of daphnia, as well as, in some cases, adhere to the
      carapace, antennae, and thoracic appendages. After 48 h of gut clearance with and
      without feeding, QD fluorescence signal was still apparent in the digestive
      tracts of daphnia, and inductively coupled plasma mass spectrometry (ICP-MS)
      measurements confirmed that 36-53% of the initial uptake was retained. As surface
      charge and pegylation can influence the uptake of nanoparticles, uptake of QDs
      coated with two different amphililic polymers and their polyethylene glycol (PEG)
      coated counterparts was also examined. Fluorescence microscopy and ICP-MS
      measurements revealed differences in uptake after 24 h of exposure which were
      attributed to particle surface coating and stability.

PMID- 20131898
TI  - Fate of PCB congeners in an industrial harbor of Lake Michigan.
AB  - We have quantified the release of polychlorinated biphenyls (PCBs) from Indiana
      Harbor and Ship Canal (IHSC) to Lake Michigan and the atmosphere. Navigational
      dredging is planned for this system, and there is concern that dredging will
      result in releases of PCBs. We have analyzed greater than 158 PCBs in surficial
      sediment, water, suspended particles, and air. We predicted the release of PCBs
      from sediments to water and from water to air. To quantify the level of
      confidence in our calculations, we used a Monte Carlo simulation for each
      congener flux. We determined that 4 +/- 0.05 kg of summation operatorPCBs were
      released from the sediment to the water and 7 +/- 0.1 kg of summation
      operatorPCBs were volatilized from the water to the air annually. We measured
      input from the upstream regions of the canal system of 45.0 kg yr(-1) and export
      to Lake Michigan of 43.9 kg yr(-1). The summation operatorPCBs mass balance
      accounts for nearly all the PCB inputs and losses to the navigational regions.
      The congener profiles in sediment, water, and air support our determination that
      the contaminated sediment is a major source of PCBs into the water and air above
      it. We have shown that the system is currently a significant source of PCBs to
      the air and to Lake Michigan, even under quiescent conditions.

PMID- 20131899
TI  - Total synthesis of the ammosamides.
AB  - The ammosamides A-C are chlorinated pyrrolo[4,3,2-de]quinoline metabolites
      isolated from the marine-derived Streptomyces strain CNR-698. The natural
      products, which possess a dense array of heteroatoms, were synthesized in 17-19
      steps from 4-chloroisatin. That the five nitrogen atoms were introduced at the
      appropriate time and in a suitable oxidation state was key to the success of the
      total synthesis. Compared to synthetic deschloro ammosamide B, natural ammosamide
      B is much less susceptible to oxidative degradation.

PMID- 20131900
TI  - Iridium-catalyzed alpha-alkylation of acetates with primary alcohols and diols.
AB  - Acetates were successfully alkylated with primary alcohols and alpha,omega-diols
      in the presence of tert-BuOK under the influence of [IrCl(cod)](2). For instance,
      the reaction of tert-butyl acetate with n-butanol in the presence of tert-BuOK as
      a base and [IrCl(cod)](2) as a catalyst in tert-BuOH at 100 degrees C produced
      tert-butyl hexanoate in good yield. When the alpha,omega-diol 1,9-nonanediol was
      employed, di-tert-butyl tridecanoate was obtained. These reactions are the first
      report of the alkylation of acetates using alcohols as alkylating agents. This
      method provides a very convenient direct route to carboxylates, which are very
      important raw materials in organic and industrial chemistry.

PMID- 20131901
TI  - Moving beyond the banks: hyporheic restoration is fundamental to restoring
      ecological services and functions of streams.
AB  - Stream restoration needs to consider the hyporheic zone just as much as the
      surface and benthic regions.

PMID- 20131902
TI  - Effects of crop nutrition on wheat grain composition and end use quality.
AB  - Increasing applications of nitrogen fertilizer to wheat (from 0 to 288 kg/ha)
      resulted in an increased proportion of gliadin proteins and increased dough
      extensibility. Flour from a plot receiving 192 kg/ha N (and no S) was similar to
      that from a plot receiving 192 kg/ha N and 53 kg/ha S, but the proportion of
      omega-gliadins was increased and dough strength was more similar to that from
      plots with lower N. The grain %N from a plot receiving 35 t/ha farmyard manure
      was similar to that from the plot receiving 144 kg/ha N, indicating that much of
      the applied N was unavailable. The protein composition and dough properties of
      flour from this plot were similar to those of grain from conventionally
      fertilized plots with similar grain N contents. Similar differences in grain N
      content, protein composition, and functional properties were observed in grain
      samples from commercial organic and conventional farms.

PMID- 20131903
TI  - Synthesis of nalidixic acid based hydrazones as novel pesticides.
AB  - Thirty-one substituted hydrazones of nalidixic acid hydrazide were synthesized
      and characterized by spectral techniques. These compounds were evaluated for
      various biological activities, namely, fungicidal, insecticidal, and
      nitrification inhibitory activities. The antifungal activity was evaluated
      against five pathogenic fungi, namely, Rhizoctonia bataticola , Sclerotium
      rolfsii , Rhizoctonia solani , Fusarium oxysporum , and Alternaria porii . They
      showed maximum inihibition against A. porii with ED(50) = 34.2-151.3 microg/mL.
      The activity was comparable to that of a commercial fungicide, hexaconazole
      (ED(50) = 25.4 microg/mL). They were also screened for insecticidal activity
      against third-instar larvae of Spodoptera litura and adults of Callosobruchus
      maculatus and Tribollium castaneum . Most of them showed 70-100% mortality
      against S. litura through feeding method at 0.1% dose. These compounds were not
      found to be effective nitrification inhibitors.

PMID- 20131904
TI  - 2-(Acetoxymethyl)buta-2,3-dienoate, a versatile 1,4-biselectrophile for phosphine
      catalyzed (4 + n) annulations with 1,n-Bisnucleophiles (n = 1, 2).
AB  - A novel PPh(3)-catalyzed (4 + n) annulation of 2-(acetoxymethyl)buta-2,3
      dienoates 1c-e with 1,n-bisnucleophiles (n = 1, 2) has been developed to provide
      a facile synthetic method for cyclopentene and 1,2,3,6-tetrahydropyridazine
      derivatives. The acetate group of 2-(acetoxymethyl)buta-2,3-dienoate is crucial
      for the formation of 1,4-biselectrophilic intermediate C, which is recognized to
      be a 1,4-biselectrophile that can react with 1,n-bisnucleophiles. Deuterium
      studies also suggest that the reaction pathway involves a proton-transfer
      process.

PMID- 20131905
TI  - Incorporation of fluorinated phenylalanine generates highly specific inhibitor of
      proteasome's chymotrypsin-like sites.
AB  - Proteasomal processing is conducted by three individual catalytic subunits,
      namely beta1, beta2, and beta5. Subunit-specific inhibitors are useful tools in
      dissecting the role of these individual subunits and are leads toward the
      development of antitumor agents. We here report that the presence of fluorinated
      phenylalanine derivatives in peptide based proteasome inhibitors has a profound
      effect on inhibitor potency and selectivity. Specifically, compound 4a emerges as
      one of the most beta5 specific inhibitors known to date.

PMID- 20131906
TI  - Graphene and mobile ions: the key to all-plastic, solution-processed light
      emitting devices.
AB  - The emerging field of "organic" or "plastic" electronics has brought low-voltage,
      ultrathin, and energy-efficient lighting and displays to market as organic light
      emitting diode (OLED) televisions and displays in cameras and mobile phones.
      Despite using carbon-based materials as the light-emitting layer, previous
      efficient organic electronic light-emitting devices have required at least one
      metal electrode. Here, we utilize chemically derived graphene for the transparent
      cathode in an all-plastic sandwich-structure device, similar to an OLED, called a
      light-emitting electrochemical cell (LEC). Using a screen-printable conducting
      polymer as a partially transparent anode and a micrometer-thick active layer
      solution-deposited from a blend of a light-emitting polymer and a polymer
      electrolyte, we demonstrate a light-emitting device based solely on solution
      processable carbon-based materials. Our results demonstrate that low-voltage,
      inexpensive, and efficient light-emitting devices can be made without using
      metals. In other words, electronics can truly be "organic".

PMID- 20131907
TI  - Dominant processes during human dendritic cell maturation revealed by integration
      of proteome and transcriptome at the pathway level.
AB  - Gene expression is commonly used to study the activation of dendritic cells (DCs)
      to identify proteins that determine whether these cells induce an
      immunostimulatory or tolerogenic immune response. RNA expression, however, does
      not necessarily predict protein abundance and often requires large numbers of
      experiments for statistical significance. Proteomics provides a direct view on
      protein expression but is costly and time consuming. Here, we combined a
      comprehensive quantitative proteome and transcriptome analysis on a single batch
      of immature and cytokine cocktail matured human DCs and integrated resulting data
      sets at the pathway level. Although overall correlation between differential mRNA
      and protein expression was low, correlation between components of DC relevant
      pathways was significantly higher. Differentially expressed proteins and genes
      partly mapped to identical but also to different pathway components demonstrating
      that RNA and protein data not only supported but also complemented each other. We
      identified 5 dominant pathways, which confirmed the importance of cytokines, cell
      adhesion, and migration in DC maturation and also indicated a fundamental role
      for lipid metabolism. From these pathways we extracted novel maturation markers
      that might improve DC vaccine design. For several of the candidate markers we
      confirmed widespread significance examining DCs from multiple individuals,
      underscoring the validity of our approach. We conclude that integration of
      different but related data sets at the pathway level can significantly increase
      the predictive power of multi "omics" analyses.

PMID- 20131909
TI  - Phase perfection in zinc Blende and Wurtzite III-V nanowires using basic growth
      parameters.
AB  - Controlling the crystallographic phase purity of III-V nanowires is notoriously
      difficult, yet this is essential for future nanowire devices. Reported methods
      for controlling nanowire phase require dopant addition, or a restricted choice of
      nanowire diameter, and only rarely yield a pure phase. Here we demonstrate that
      phase-perfect nanowires, of arbitrary diameter, can be achieved simply by
      tailoring basic growth parameters: temperature and V/III ratio. Phase purity is
      achieved without sacrificing important specifications of diameter and dopant
      levels. Pure zinc blende nanowires, free of twin defects, were achieved using a
      low growth temperature coupled with a high V/III ratio. Conversely, a high growth
      temperature coupled with a low V/III ratio produced pure wurtzite nanowires free
      of stacking faults. We present a comprehensive nucleation model to explain the
      formation of these markedly different crystal phases under these growth
      conditions. Critical to achieving phase purity are changes in surface energy of
      the nanowire side facets, which in turn are controlled by the basic growth
      parameters of temperature and V/III ratio. This ability to tune crystal structure
      between twin-free zinc blende and stacking-fault-free wurtzite not only will
      enhance the performance of nanowire devices but also opens new possibilities for
      engineering nanowire devices, without restrictions on nanowire diameters or
      doping.

PMID- 20131908
TI  - Structure of the dominant negative S17N mutant of Ras.
AB  - The use of the dominant negative mutant of Ras has been crucial in elucidating
      the cellular signaling of Ras in response to the activation of various membrane
      bound receptors. Although several point mutants of Ras exhibit a dominant
      negative effect, the asparagine to serine mutation at position 17 (S17N) remains
      the most popular and the most effective at inhibiting the activation of
      endogenous Ras. It is now widely accepted that the dominant negative effect is
      due to the ability of the mutant to sequester upstream activators and its
      inability to activate downstream effectors. Here, we present the crystal
      structure of RasS17N in the GDP-bound form. In the three molecules that populate
      the asymmetric unit, the Mg(2+) ion that normally coordinates the beta-phosphate
      is absent because of steric hindrance from the Asn17 side chain. Instead, a
      Ca(2+) ion is coordinating the alpha-phosphate. Also absent from one molecule is
      electron density for Phe28, a conserved residue that normally stabilizes the
      nucleotide's guanine base. Except for Phe28, the nucleotide makes conserved
      interactions with Ras. Combined, the inability of Phe28 to stabilize the guanine
      base and the absence of a Mg(2+) ion to neutralize the negative charges on the
      phosphates explain the weaker affinity of GDP for Ras. Our data suggest that the
      absence of the Mg(2+) should also dramatically affect GTP binding to Ras and the
      proper positioning of Thr35 necessary for the activation of switch 1 and the
      binding to downstream effectors, a prerequisite for the triggering of signaling
      pathways.

PMID- 20131910
TI  - TagRecon: high-throughput mutation identification through sequence tagging.
AB  - Shotgun proteomics produces collections of tandem mass spectra that contain all
      the data needed to identify mutated peptides from clinical samples. Identifying
      these sequence variations, however, has not been feasible with conventional
      database search strategies, which require exact matches between observed and
      expected sequences. Searching for mutations as mass shifts on specified residues
      through database search can incur significant performance penalties and generate
      substantial false positive rates. Here we describe TagRecon, an algorithm that
      leverages inferred sequence tags to identify unanticipated mutations in clinical
      proteomic data sets. TagRecon identifies unmodified peptides as sensitively as
      the related MyriMatch database search engine. In both LTQ and Orbitrap data sets,
      TagRecon outperformed state of the art software in recognizing sequence
      mismatches from data sets with known variants. We developed guidelines for
      filtering putative mutations from clinical samples, and we applied them in an
      analysis of cancer cell lines and an examination of colon tissue. Mutations were
      found in up to 6% of identified peptides, and only a small fraction corresponded
      to dbSNP entries. The RKO cell line, which is DNA mismatch repair deficient,
      yielded more mutant peptides than the mismatch repair proficient SW480 line.
      Analysis of colon cancer tumor and adjacent tissue revealed hydroxyproline
      modifications associated with extracellular matrix degradation. These results
      demonstrate the value of using sequence tagging algorithms to fully interrogate
      clinical proteomic data sets.

PMID- 20131911
TI  - Proteomic analysis of an interactome for long-form AMPA receptor subunits.
AB  - Glutamate receptors of the AMPA-type mediate fast excitatory synaptic
      transmission in the central nervous system and play key roles in synaptic
      plasticity. The binding of these receptors to a variety of proteins is known to
      regulate their targeting to the synapse and consequently to modulate synaptic
      strength, as well as to modify receptor characteristics. In this study, a
      proteomic screening was conducted in order to identify new binding partners for
      GluR4 AMPA receptor subunit. Immunoprecipitation of GluR4 and associated proteins
      was performed using rat cerebellum lysates and an heterologous systems
      overexpressing GluR4 AMPA receptor subunit. Isolated immuno-complexes were
      resolved by 1-D SDS-PAGE, and analyzed by liquid chromatography tandem mass
      spectrometry (LC-MS/MS). This approach led to the identification of several
      interactors, most of which are novel AMPA receptor partners, namely, cytoskeleton
      proteins, motor proteins, RNA processing proteins which are part of neuronal RNA
      granules, and kinases, among others. This study unravels new constituents of the
      macromolecular complex of long-form calcium-permeable AMPA receptors.

PMID- 20131912
TI  - Evidence of altered guinea pig ventricular cardiomyocyte protein expression and
      growth in response to a 5 min in vitro exposure to H(2)O(2).
AB  - Oxidative stress and alterations in cellular calcium homeostasis are associated
      with the development of cardiac hypertrophy. However, the early cellular
      mechanisms for the development of hypertrophy are not well understood. Guinea pig
      ventricular myocytes were exposed to 30 microM H(2)O(2) for 5 min followed by 10
      units/mL catalase to degrade the H(2)O(2), and effects on protein expression were
      examined 48 h later. Transient exposure to H(2)O(2) increased the level of
      protein synthesis more than 2-fold, assessed as incorporation of [(3)H]leucine (n
      = 12; p < 0.05). Cell size was increased slightly, but there was no evidence of
      major cytoskeletal disorganization assessed using fluorescence microscopy.
      Changes in the expression of individual proteins were assessed using iTRAQ
      protein labeling followed by mass spectrometry analysis (LC-MALDI-MSMS); 669
      proteins were identified, and transient exposure of myocytes to H(2)O(2) altered
      expression of 35 proteins that were predominantly mitochondrial in origin,
      including TCA cycle enzymes and oxidative phosphorylation proteins. Consistent
      with changes in the expression of mitochondrial proteins, transient exposure of
      myocytes to H(2)O(2) increased the magnitude of the mitochondrial NADH signal
      10.5 +/- 2.3% compared to cells exposed to 0 microM H(2)O(2) for 5 min followed
      by 10 units/mL catalase (n = 8; p < 0.05). In addition, metabolic activity was
      significantly increased in the myocytes 48 h after transient exposure to
      H(2)O(2), assessed as formation of formazan from tetrazolium salt. We conclude
      that a 5 min exposure of ventricular myocytes to 30 microM H(2)O(2) is sufficient
      to significantly alter protein expression, consistent with the development of
      hypertrophy in the myocytes. Changes in mitochondrial protein expression and
      function appear to be early sequelae in the development of hypertrophy.

PMID- 20131913
TI  - Multisite phosphorylation of voltage-gated sodium channel alpha subunits from rat
      brain.
AB  - Reversible phosphorylation of ion channels underlies cellular plasticity in
      mammalian neurons. Voltage-gated sodium or Nav channels underlie action potential
      initiation and propagation, dendritic excitability, and many other aspects of
      neuronal excitability. Various protein kinases have been suggested to
      phosphorylate the primary or alpha subunit of Nav channels, affecting diverse
      aspects of channel function. Previous studies of Nav alpha subunit
      phosphorylation have led to the identification of a small set of phosphorylation
      sites important in mediating diverse aspects of Nav channel function. Here we use
      nanoflow liquid chromatography tandem mass spectrometry (nano-LC MS/MS) on Nav
      alpha subunits affinity-purified from rat brain with two distinct monoclonal
      antibodies to identify 15 phosphorylation sites on Nav1.2, 12 of which have not
      been previously reported. We also found 3 novel phosphorylation sites on Nav1.1.
      In general, commonly used phosphorylation site prediction algorithms did not
      accurately predict these novel in vivo phosphorylation sites. Our results
      demonstrate that specific Nav alpha subunits isolated from rat brain are highly
      phosphorylated, and suggest extensive modulation of Nav channel activity in
      mammalian brain. Identification of phosphorylation sites using monoclonal
      antibody-based immunopurification and mass spectrometry is an effective approach
      to define the phosphorylation status of Nav channels and other important membrane
      proteins in mammalian brain.

PMID- 20131914
TI  - Effect of electron-withdrawing dithiolate bridge on the electron-transfer steps
      in diiron molecules related to [2Fe](H) subsite of the [FeFe]-hydrogenases.
AB  - Two hexacarbonyl diiron compounds featuring dithiolate bridges with strong
      electron-withdrawing groups (CO(2)Me, tetrachloro-biphenyl) were synthesized and
      structurally characterized. Electrochemical study of these compounds demonstrates
      that such electron-withdrawing groups have a pronounced effect on both the
      reduction potentials and the electron transfer process. The reduced forms of
      these compounds catalyze the reduction of protons in dichloromethane. However,
      the tetrachloro-biphenyl derivative is the only one able to work in the potential
      range of its primary reduction process. A catalytic reaction scheme is proposed.

PMID- 20131915
TI  - Synthesis and reactivity of rhodium(II) N-triflyl azavinyl carbenes.
AB  - Highly reactive rhodium(II) N-trifluoromethylsulfonyl azavinyl carbenes are
      formed in situ from NH-1,2,3-triazoles, triflic anhydride, and rhodium
      carboxylates. They rapidly and selectively react with olefins, providing
      cyclopropane carboxaldehydes and 2,3-dihydropyrroles in generally excellent
      yields and high enantio- and diastereoselectivity.

PMID- 20131916
TI  - DNA release dynamics from bioreducible layer-by-layer films.
AB  - DNA release dynamics from layer-by-layer (LbL) films is an important aspect to
      consider with regards to localized gene delivery systems. The rate of DNA release
      and the condensation state of DNA during release are of particular interest in
      the field of gene delivery. A hyperbranched poly(amido amine) (RHB) containing
      bioreducible disulfide bonds is used to form interpolyelectrolyte complexes with
      DNA during LbL film assembly. During film disassembly, DNA is released in
      physiologic conditions due to the reducing nature of the RHB. Uncondensed DNA
      deposited on the surface was compared to DNA condensed by RHB in polyplex form by
      using two types of LbL films, RHB/DNA/RHB and polyplex terminated films,
      RHB/DNA/polyplex. LbL films with up to three layers are used in order to
      facilitate high-resolution atomic force microscopy (AFM) imaging. X-ray
      reflectivity, ellipsometry, and Fourier transform infrared spectroscopy are also
      used. The film disassembly, rearrangement, and release of molecules from the
      surface due to thiol-disulfide exchange is conducted in reducing dithiothreitol
      (DTT) solutions. Salt is found to accelerate the overall rate of film
      disassembly. Additionally, it was found that the polyplex layer disassembles
      faster than the DNA layer. The predominant intermediate structure is the toroid
      structure for the polyplex layer and the fiber bundle structure for the DNA layer
      during film disassembly. This study offers a simple means to modulate DNA release
      from LbL films by utilizing both condensed and uncondensed DNA in different
      layers. The study highlights nanostructures, toroids, and bundles as dominant
      intermediate DNA structures during DNA release from LbL films.

PMID- 20131917
TI  - Effect of substrate surface reconstruction on interaction with adsorbates: Pt on
      6H-SiC(0001).
AB  - Three reconstructed 6H-SiC(0001) surfaces, including a Si-rich 3 x 3 surface, a C
      rich 6 square root(3) x 6 square root(3) surface, and a graphitized SiC surface,
      were used as substrates for the deposition of Pt overlayers. The interaction
      between Pt and the SiC(0001) surfaces was studied by X-ray photoelectron
      spectroscopy (XPS) and scanning tunneling microscopy (STM). Pt reacts readily
      with the 3 x 3 surface to form platinum silicide even at room temperature. On the
      graphitized SiC surface, metal particles with low lateral dispersion form and
      keep on aggregating upon annealing. In contrast, homogeneously distributed small
      Pt nanoclusters were grown on the C-rich 6 square root(3) x 6 square root(3)
      surface. The unique nanomesh surface structure helps to stabilize the Pt
      nanoclusters until 800 degrees C. Above 1000 degrees C, Pt tends to diffuse into
      the subsurface region, forming the C/Pt silicide/SiC(0001) interface structure.
      The different surface electronic structures of the three Pt/SiC(0001) systems
      were discussed as well. The present data show that surface reconstruction
      provides an effective route to control the growth of metal overlayers and the
      formation of metal/substrate interfaces.

PMID- 20131918
TI  - Magnetic doping and kondo effect in bi(2)se(3) nanoribbons.
AB  - A simple surface band structure and a large bulk band gap have allowed Bi2Se3 to
      become a reference material for the newly discovered three-dimensional
      topological insulators, which exhibit topologically protected conducting surface
      states that reside inside the bulk band gap. Studying topological insulators such
      as Bi2Se3 in nanostructures is advantageous because of the high surface-to-volume
      ratio, which enhances effects from the surface states; recently reported Aharonov
      Bohm oscillation in topological insulator nanoribbons by some of us is a good
      example. Theoretically, introducing magnetic impurities in topological insulators
      is predicted to open a small gap in the surface states by breaking time-reversal
      symmetry. Here, we present synthesis of magnetically doped Bi2Se3 nanoribbons by
      vapor-liquid-solid growth using magnetic metal thin films as catalysts. Although
      the doping concentration is less than approximately 2%, low-temperature transport
      measurements of the Fe-doped Bi2Se3 nanoribbon devices show a clear Kondo effect
      at temperatures below 30 K, confirming the presence of magnetic impurities in the
      Bi2Se3 nanoribbons. The capability to dope topological insulator nanostructures
      magnetically opens up exciting opportunities for spintronics.

PMID- 20131919
TI  - On-chip interferometric detection of nanomechanical motion.
AB  - An integrable on-chip displacement transduction of nanomechenical motion is
      developed that senses the modulation of the optical near-field of an illuminated
      vibrating string with a nearby Schottky photodiode. This scheme poses no
      restrictions on resonator material and avoids additional damping. The achieved
      sensitivity of 1 pm/Hz(1/2) enables the detection of Brownian motion of our
      mechanical resonators at room temperature. Implementing a feedback scheme of the
      detected signal into the electrical actuation, we demonstrate self-oscillation.

PMID- 20131920
TI  - Tuning hydrated nanoceria surfaces: experimental/theoretical investigations of
      ion exchange and implications in organic and inorganic interactions.
AB  - Long-term stability and surface properties of colloidal nanoparticles have
      significance in many applications. Here, surface charge modified hydrated cerium
      oxide nanoparticles (CNPs, also known as nanoceria) are synthesized, and their
      dynamic ion exchange interactions with the surrounding medium are investigated in
      detail. Time-dependent zeta (zeta) potential (ZP) variations of CNPs are
      demonstrated as a useful characteristic for optimizing their surface properties.
      The surface charge reversal of CNPs observed with respect to time, concentration,
      temperature, and doping is correlated to the surface modification of CNPs in
      aqueous solution and the ion exchange reaction between the surface protons (H(+))
      and the neighboring hydroxyls ions (OH(-)). Using density functional theory (DFT)
      calculations, we have demonstrated that the adsorption of H(+) ions on the CNP
      surface is kinetically more favorable while the adsorption of OH(-) ions on CNPs
      is thermodynamically more favorable. The importance of selecting CNPs with
      appropriate surface charges and the implications of dynamic surface charge
      variations are exemplified with applications in microelectronics and biomedical.

PMID- 20131921
TI  - Composition-dependent formation of platinum silver nanowires.
AB  - The understanding of shape control of colloidal nanoparticles is still rather
      limited even after well over a decade of intensive research efforts. While
      surface capping agents can greatly influence the growth habit of nanocrystals in
      solution, the formation of certain morphology can hardly be understood based on
      both experimental data and simulations. Without a good understanding of the
      origins for shape formation, deterministic approaches to the synthesis of
      nanostructures can be hard to realize. In this paper, we describe the synthesis
      and formation of PtAg alloy nanowires in the presence of oleylamine and oleic
      acid through the oriented attachment. Transmission electron microscopy study
      shows the formation of wormlike nanowires occurs largely at the composition
      around Pt(50)Ag(50). Both Pt and Ag rich alloy nanostructures form sphere-like or
      faceted nanoparticles under the same reaction conditions. Density functional
      theory calculation is used to understand the interactions between the functional
      groups of capping agents and low index planes of PtAg alloys. The structural
      order of interfaces after collision between primary particles is obtained by
      molecular dynamic simulation. The results indicate that the formation of alloy
      nanowires is mostly driven by the interplay between the binding energy of capping
      agents on alloy surfaces and the diffusion of atoms at the interface upon the
      collision of primary nanoparticles.

PMID- 20131922
TI  - Role of hydroxyl groups in the NH(x) (x = 1-3) adsorption on the TiO2 anatase
      (101) surface determined by a first-principles study.
AB  - A spin-polarized density functional theory calculation was carried out to study
      the adsorption of NH(x) species (x = 1-3) on a TiO2 anatase (101) surface with
      and without hydroxyl groups by using first-principles calculations. It was found
      that the present hydroxyl group has the effect of significantly enhancing the
      adsorption of monodentate adsorbates H2N-Ti(a) compared to that on a bare
      surface. The nature of the interaction between the adsorbate (NH(x)) and the
      hydroxylated or bare surface was analyzed by the Mulliken charge and density of
      states (DOS) calculations. This facilitation of NH2 is caused by the donation of
      coadsorbed H filling the nonbonding orbital of NH2, resulting in an electron gain
      in NH2 from the bonding. In addition, the upper valence band, which originally
      consisted of the mixing of O 2p and Ti 3d orbitals, has been broadened by the two
      adjacent H 1s and NH2 sigma(y)(b) orbitals joined to the bottom of the original
      TiO2 valence band. The results are important to understand the OH effect in
      heterogeneous catalysis.

PMID- 20131923
TI  - Optimal management of incontinence-associated dermatitis in the elderly.
AB  - Incontinence-associated dermatitis (IAD), sometimes referred to as perineal
      dermatitis, is an inflammation of the skin associated with exposure to urine or
      stool. Elderly adults, and especially those in long-term care facilities, are at
      risk for urinary or fecal incontinence and IAD. Traditionally, IAD has received
      little attention as a distinct disorder, and it is sometimes confused with stage
      I or II pressure ulcers. However, a modest but growing body of research is
      beginning to provide insights into the epidemiology, etiology, and
      pathophysiology of IAD. In addition, recent changes in reimbursement policies
      from the US Center for Medicare and Medicaid Services regarding pressure ulcer
      prevention has focused attention on the differential diagnosis of IAD versus
      pressure ulcer, and its influence on pressure ulcer risk. Color, location, depth,
      and the presence or absence of necrotic tissue are visual indicators used to
      differentiate IAD from pressure-related skin damage. Prevention is based on
      avoiding or minimizing exposure to stool or urine combined with a structured skin
      care program based on principles of gentle cleansing, moisturization, preferably
      with an emollient, and application of a skin protectant. Treatment of IAD focuses
      on three main goals: (i) removal of irritants from the affected skin; (ii)
      eradication of cutaneous infections such as candidiasis; and (iii) containment or
      diversion of incontinent urine or stool.

PMID- 20131924
TI  - Alitretinoin for severe chronic hand eczema: a NICE single technology appraisal.
AB  - The National Institute for Health and Clinical Excellence (NICE) invited the
      manufacturer of alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to
      submit evidence for the clinical and cost effectiveness of this drug for the
      treatment of patients with severe chronic hand eczema (CHE), as part of the
      Institute's single technology appraisal (STA) process. The Centre for Reviews and
      Dissemination and the Centre for Health Economics at the University of York were
      commissioned to act as the Evidence Review Group (ERG). This article provides a
      description of the company submission, the ERG review and NICE's subsequent
      decisions. The ERG produced a critical review of the evidence for the clinical
      and cost effectiveness of the technology based upon the manufacturer's submission
      to NICE. The ERG also independently searched for relevant evidence and modified
      the manufacturer's decision analytic model to examine the impact of altering some
      of the key assumptions. The main clinical effectiveness data were derived from a
      single-placebo randomized controlled trial (RCT) of daily treatment with
      alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients
      with severe CHE unresponsive to topical corticosteroids. A significantly greater
      proportion of patients achieved 'clear' or 'almost clear' hands by week 24 with
      alitretinoin than those using placebo: 48% with alitretinoin 30 mg (p < 0.001);
      28% with alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who
      responded remained in remission during the 24-week follow-up period. The most
      commonly reported adverse event was dose-dependent headache, with rates of 20% in
      the alitretinoin 30 mg group and 11% in the alitretinoin 10 mg group,
      respectively. Serious adverse events were rare, although alitretinoin was
      associated with increases in both total cholesterol and triglycerides. No direct
      or indirect comparisons of alitretinoin with any of the relevant treatment
      comparators (psoralen + UVA [PUVA], ciclosporin or azathioprine) were available.
      In the manufacturer's original submission to NICE, the base-case incremental cost
      effectiveness ratios (ICERs) reported for alitretinoin were pound8614 per QALY
      versus ciclosporin, - pound469 per QALY versus PUVA (with alitretinoin dominant)
      and pound10 612 per QALY versus azathioprine (year 2007-8 values). In response to
      a request from the ERG, the manufacturers provided a revised model that compared
      alitretinoin only with placebo, for which the ICER was reported to be pound12
      931. However, the omission of adverse events entirely from this revised model, in
      combination with a number of other factors, led the ERG to conclude that the
      model underestimated the costs of treatment associated with alitretinoin.
      Estimates of health-related quality of life (HR-QOL) were the primary source of
      uncertainty, with the use of values from an alternative source producing ICERs of
      around pound30 000 per QALY gained. The ERG concluded that, although the evidence
      presented indicates that alitretinoin is efficacious in the treatment of severe
      CHE, it gives little indication of alitretinoin's efficacy relative to likely
      alternative treatment options or its efficacy and safety in the longer term.
      Although the ICERs estimated by the manufacturer suggested that alitretinoin may
      be cost effective for use in the UK NHS, utilizing the alternative HR-QOL
      estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable
      uncertainty as to the true ICER of alitretinoin versus the relevant treatment
      comparators. The Appraisal Committee recommended that alitretinoin be provided to
      those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score
      of at least 15. They recommended that treatment be stopped as soon as an adequate
      response was observed, or if CHE remained severe at 12 weeks, or if response was
      inadequate at 24 weeks.

PMID- 20131925
TI  - Cost effectiveness of respiratory syncytial virus prophylaxis: a critical and
      systematic review.
AB  - Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization
      in the US. The economic burden of severe disease is substantial, including
      hospitalization costs and out-of-pocket expenses. RSV prophylaxis with either RSV
      immune globulin intravenous (RSV-IGIV) or palivizumab has been shown to be
      effective in reducing RSV-related hospitalizations. Motavizumab, a new enhanced
      potency humanized RSV monoclonal antibody, is presently in clinical trials. RSV
      IGIV and palivizumab are associated with high acquisition costs. Cost
      effectiveness analyses are therefore of great importance in helping to determine
      who should receive RSV prophylaxis. Six studies have analysed the cost
      effectiveness of RSV-IGIV, 14 have analysed the cost effectiveness of palivizumab
      and five have analysed the cost effectiveness of both agents, two of which
      directly compared palivizumab with RSV-IGIV. The cost effectiveness of
      motavizumab has not been studied. Significant variation exists in the modelling
      used in these analyses. Many studies have examined short-term benefits such as
      reducing hospitalizations and associated costs, while fewer studies have examined
      long-term benefits such as QALYs or life-years gained. The payer and society have
      been the most common perspectives used. The endpoints examined varied and
      generally did not account for the potential impact of RSV prophylaxis on RSV
      related complications such as asthma. While some studies have reported acceptable
      cost-effectiveness ratios for RSV prophylaxis, the majority failed to show cost
      savings or cost-effectiveness ratios below commonly accepted thresholds for
      either RSV-IGIV or palivizumab. Cost effectiveness of RSV prophylaxis tended to
      be more favourable in populations with specific risk factors, including premature
      infants < or =32 weeks' gestational age, and infants or children aged < 2 years
      with chronic lung disease or congenital heart disease. Comparing the results of
      economic analyses of the two agents suggests palivizumab may be the more cost
      effective option in the population for which RSV prophylaxis is recommended. Over
      time, the acquisition cost of RSV prophylaxis agents, a major cost driver, may
      decrease, and more acceptable outcomes of economic analyses may result. Albeit
      important, the results of economic analyses are not the only tool that decision
      makers rely on, as population-specific risk factors, and efficacy and safety data
      must be considered when developing treatment guidelines and making clinical
      decisions.

PMID- 20131927
TI  - Ontogenetic development of cardiac tolerance to oxygen deprivation - possible
      mechanisms.
AB  - Our present focus on the hypoxic immature heart is driven by clinical urgency:
      cyanotic congenital cardiac malformations remain the single largest cause of
      mortality from congenital defects and ischemic heart disease is no more the
      disease of the fifth and older decades but its origin as well as risk factors are
      present already during early ontogeny. Moreover, the number of adult patients
      operated for cyanotic congenital heart disease during infancy steadily increases.
      This group approaches the age of the rising risk of serious cardiovascular
      diseases, particularly ischemic heart disease. Experimental results have clearly
      shown that the immature heart is significantly more tolerant to oxygen deficiency
      than the adult myocardium. However, the mechanisms of this difference have not
      yet been satisfactorily clarified; they are likely the result of developmental
      changes in cardiac energy metabolism, including mitochondrial function. The high
      resistance of the newborn heart cannot be further increased by ischemic
      preconditioning or adaptation to chronic hypoxia; these protective mechanisms
      appear only with decreasing tolerance during development. Resistance of the adult
      myocardium to acute oxygen deprivation may be significantly influenced by
      perinatal hypoxia. These results suggest that the developmental approach offers
      new possibilities in the studies of pathogenesis, prevention and therapy of
      critical cardiovascular diseases.

PMID- 20131928
TI  - Apolipoprotein A5 in health and disease.
AB  - High plasma levels of triglycerides (TG) are an independent risk factor in the
      development of cardiovascular disease, with about 50 % of the final levels being
      determined genetically. Apolipoprotein A5 (APOA5) is the last discovered member
      of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing
      analysis. The importance of APOA5 gene for determination of plasma triglyceride
      levels has been suggested after development of transgenic and knock-out mice
      (transgenic mice displayed significantly reduced TG, whereas knock-out mice had
      high TG). In Czech population, alleles C-1131 and Trp19 are associated with
      elevated levels of plasma TG and higher risk of myocardial infarction
      development. These alleles also play some role in nutrigenetics and actigenetics
      of lifestyle interventions leading to the plasma cholesterol changes as well as
      in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations
      detected in Czech population did not show strict effect on plasma TG levels.
      Val153 --> Met variant exhibit the sex-specific effect of HDL-cholesterol levels.
      The suggested roles of APOA5 variants in determination of the plasma remnant
      particles, plasma concentrations of C-reactive protein or some anthropometrical
      parameters were excluded.

PMID- 20131929
TI  - Proinflammatory status, genetics and atherosclerosis.
AB  - Over the last decade, C-reactive protein concentration analyzed by the high
      sensitivity method (hsCRP) has been proven as a marker of premature
      atherosclerosis. Concentration exceeding 2 mg/l represents an increased
      individual risk of myocardial infarction and stroke but strict application of
      this borderline is complicated by relations of CRP concentrations to other risk
      factors of cardiovascular diseases. In a large 1 % representative sample of the
      Czech population, a positive relation of hsCRP to BMI, a waist circumference and
      triglyceride concentration was documented. Substantial sex differences were found
      in its relationship to age. Whereas it is continuously increasing in men, this
      increase appears in women only after menopause. A substantial decrease of body
      weight and visceral fat volume by increased physical activity is accompanied by
      significant decrease of hsCRP in young obese women. This decrease was not related
      to a change of interleukin-6 concentration, although it is supposed to regulate
      CRP production. CRP concentration is partly under genetic control as a higher
      concentration in young siblings of probands with proved coronary atherosclerosis
      was documented. The participation of genes related to lipoprotein metabolism
      (genes for apolipoprotein CI and apolipoprotein E) influence hsCRP
      concentrations. We hypothesized that an increased concentration of hsCRP
      represents a certain marker of proinflammatory status related to central obesity
      and triglyceride metabolism and it might be related to individual properties of
      monocytes in atherogenesis.

PMID- 20131930
TI  - Blood vessel replacement: 50 years of development and tissue engineering
      paradigms in vascular surgery.
AB  - The gold standard material in bypass surgery of blood vessels remains the
      patient's own artery or vein. However, this material may be unavailable, or may
      suffer vein graft disease. Currently available vascular prostheses, namely
      polyethylene terephthalate (PET, Dacron) and expanded polytetrafluoroethylene
      (ePTFE), perform well as large-caliber replacements, but their long-term patency
      is discouraging in small-caliber applications (<6 mm), such as in coronary,
      crural or microvessel surgery. This failure is mainly a result of an unfavorable
      healing process with surface thrombogenicity, due to lack of endothelial cells
      and anastomotic intimal hyperplasia caused by hemodynamic disturbances. An ideal
      small-diameter vascular graft has become a major focus of research. Novel
      biomaterials have been manufactured, and tissue-biomaterial interactions have
      been optimized. Tissue engineering technology has proven that the concept of
      partially or totally living blood vessels is feasible. The purpose of this review
      is to outline the vascular graft materials that are currently being implanted,
      taking into account cell-biomaterial physiology, tissue engineering approaches
      and the collective achievements of the authors.

PMID- 20131931
TI  - Myocardial phospholipid remodeling under different types of load imposed during
      early postnatal development.
AB  - Normal increase in hemodynamic load during early postnatal life is associated
      with heart growth and maturation of membrane structures that is accompanied by
      remodeling of membrane protein and lipid components. This review describes
      remodeling of phospholipids (PL) in rat myocardium during normal postnatal
      development and during accelerated cardiac growth induced by additional workload
      (aorta constriction, chronic hypoxia and hyperthyroidism) imposed on the heart
      early after birth. Normal physiological load after birth stimulates the
      development of membrane structures and synthesis of PL. While hyperthyroidism
      accelerates these processes, pressure overload has an inhibitory effect. These
      changes primarily influence the maturation of mitochondrial membranes as
      cardiolipin is one of the most affected PL species. The most sensitive part of PL
      structure in their remodeling process are PL acyl chains, particularly
      polyunsaturated fatty acids that are the key components determining the basic
      physicochemical properties of the membrane bilayer and thus the function of
      membrane-bound proteins and membrane-derived signaling lipid molecules. It is
      evident that PL remodeling may significantly influence both normal and
      pathological postnatal development of myocardium.

PMID- 20131932
TI  - Tissue-engineered heart valves.
AB  - Currently-used mechanical and biological heart valve prostheses have several
      disadvantages. Mechanical prostheses, based on carbon, metallic and polymeric
      components, require permanent anticoagulation treatment, and their usage often
      leads to adverse reactions, e.g. thromboembolic complications and endocarditis.
      Xenogenous and allogenous biological prostheses are associated with immune
      reaction, thrombosis and degeneration, and thus they have a high rate of
      reoperation. Biological prostheses of autologous origin, such as pulmonary
      autografts, often burden the patient with a complicated surgery and the risk of
      reoperation. Therefore, efforts are being made to prepare bioartificial heart
      valves with an autologous biological component by methods of tissue engineering.
      They should be biocompatible, durable, endowed with appropriate mechanical
      properties and able to grow with a child. For this purpose, scaffolds composed of
      synthetic materials, such as poly(lactic acid), poly(caprolactone), poly(4
      hydroxybutyrate), hydrogels or natural polymers, e.g. collagen, elastin, fibrin
      or hyaluronic acid, have been seeded with autologous differentiated, progenitor
      or stem cells. Promising results have been obtained with nanostructured
      scaffolds, and also with cultivation in special dynamic bioreactors prior to
      implantation of the bioartificial grafts into an animal organism.

PMID- 20131933
TI  - Fetal cardiology in the Czech Republic: current management of prenatally
      diagnosed congenital heart diseases and arrhythmias.
AB  - Reliable diagnosis of congenital heart defects and arrhythmias in utero has been
      possible since the introduction of fetal echocardiography. The nation-wide
      prenatal ultrasound screening program in the Czech Republic enabled detection of
      cardiac abnormalities in 1/3 of patients born with any congenital heart disease
      and up to 83 % of those with critical forms. Prenatal frequency of individual
      heart anomalies significantly differed from the postnatal frequency. Fetal
      isolated complete atrioventricular block and supraventricular tachycardia may
      lead to heart failure and are important causes of fetal mortality. The regression
      of heart failure was achieved by a conversion to the sinus rhythm in the
      supraventricular tachycardia and by increase of ventricular rate in the complete
      atrioventricular block.

PMID- 20131934
TI  - The role of cardiac surgery in treatment of chronic heart failure.
AB  - Chronic heart failure has become a significant health problem. Cardiac surgery
      has an important role in the treatment of patients with heart failure. There are
      traditional surgical techniques in cardiac surgery - coronary revascularization,
      valve surgery, ventricular reconstructive surgery as well as new surgical
      techniques - cardiac support device (CorCap), mechanical circulatory support and
      resynchronization therapy. Cardiac surgery has a definitive role in the treatment
      algorithm for chronic heart failure.

PMID- 20131935
TI  - The interaction of genetic and environmental factors in the etiology of
      hypertension.
AB  - Essential hypertension is a major risk factor for several cardiovascular
      diseases. It is a complex trait resulting from the interactions of multiple
      genetic and environmental factors. Moreover, not only genetic but also epigenetic
      inheritance plays a significant role. One can speculate that hypertension
      develops as a consequence of "errors" in well-coordinated regulatory systems of
      blood pressure. Errors in the cascade of molecular, biochemical and genetic
      processes, which regulate blood pressure, have finally enough potential to result
      in hypertension. Numerous environmental factors surrounding the organism during
      its development should influence the expression of genetic information. However,
      despite the considerable research effort, it is still difficult to identify all
      genes and/or other genetic determinants leading to essential hypertension and
      other cardiovascular diseases. This is mainly because these diseases usually
      become a medical problem in adulthood, although their roots might be traced back
      to earlier stages of ontogeny. The link between distinct developmental periods
      (e.g. birth and adulthood) should involve changes in gene expression involving
      epigenetic phenomena. The purpose of the present paper is to bring a piece of
      light on gene-environmental interactions potentially implicated in the
      pathogenesis of hypertension.

PMID- 20131936
TI  - Impaired control of L-type voltage-dependent calcium channels in experimental
      hypertension.
AB  - Blood pressure (BP) level results from the balance of vasoconstrictors (mainly
      sympathetic nervous system) and vasodilators (predominantly nitric oxide and
      endothelium-derived hyperpolarizing factor). Most of the forms of experimental
      hypertension are associated with sympathetic hyperactivity and endothelial
      dysfunction. It is evident that nitric oxide and norepinephrine are antagonists
      in the control of calcium influx through L-type voltage-dependent calcium
      channels (L-VDCC). Their effects on L-VDCC are mediated by cGMP and cAMP,
      respectively. Nevertheless, it remains to determine whether these cyclic
      nucleotides have direct effects on L-VDCC or they act through a modulation of
      calcium-activated K(+) and Cl(-) channels which influence membrane potential.
      Rats with genetic or salt hypertension are characterized by a relative (but not
      absolute) NO deficiency compared to the absolute enhancement of sympathetic
      vasoconstriction. This dysbalance of vasoconstrictor and vasodilator systems in
      hypertensive animals is reflected by greater calcium influx through L-VDCC
      susceptible to the inhibition by nifedipine. However, when the modulatory
      influence of cyclic nucleotides is largely attenuated by simultaneous ganglionic
      blockade and NO synthase inhibition, BP of spontaneously hypertensive rats
      remains still elevated compared to normotensive rats due to augmented nifedipine
      sensitive BP component. It remains to determine why calcium influx through L-VDCC
      of hypertensive rats is augmented even in the absence of modulatory influence of
      major vasoactive systems (sympathetic nervous system, nitric oxide).

PMID- 20131937
TI  - Renal interactions of renin-angiotensin system, nitric oxide and superoxide
      anion: implications in the pathophysiology of salt-sensitivity and hypertension.
AB  - Renin-angiotensin system (RAS) plays a key role in the regulation of renal
      function, volume of extracellular fluid and blood pressure. The activation of RAS
      also induces oxidative stress, particularly superoxide anion (O(2)(-)) formation.
      Although the involvement of O(2)(-) production in the pathology of many diseases
      is known for long, recent studies also strongly suggest its physiological
      regulatory function of many organs including the kidney. However, a marked
      accumulation of O(2)(-) in the kidney alters normal regulation of renal function
      and thus may contribute to the development of salt-sensitivity and hypertension.
      In the kidney, O(2)(-) acts as vasoconstrictor and enhances tubular sodium
      reabsorption. Nitric oxide (NO), another important radical that exhibits opposite
      effects than O(2)(-), is also involved in the regulation of kidney function.
      O(2)(-) rapidly interacts with NO and thus, when O(2)(-) production increases, it
      diminishes the bioavailability of NO leading to the impairment of organ function.
      As the activation of RAS, particularly the enhanced production of angiotensin II,
      can induce both O(2)(-) and NO generation, it has been suggested that
      physiological interactions of RAS, NO and O(2)(-) provide a coordinated
      regulation of kidney function. The imbalance of these interactions is critically
      linked to the pathophysiology of salt-sensitivity and hypertension.

PMID- 20131938
TI  - End-organ damage in hypertensive transgenic Ren-2 rats: influence of early and
      late endothelin receptor blockade.
AB  - The rat strain transgenic for the murine Ren-2 renin gene (TGR) is defined as a
      monogenic model of angiotensin II-dependent hypertension with endogenous
      activation of the renin-angiotensin system. Homozygous males TGR develop
      malignant hypertension with a strong salt-sensitive component. These animals show
      severe hypertension, proteinuria and high mortality. Morphological changes of
      renal parenchyma correspond to chronic ischemic glomerular changes. Heterozygous
      TGR develop only mild hypertension and thus provide a more suitable model of
      hypertension regarding to clinical studies. Within the renal parenchyma,
      secondary focal segmental glomerulosclerosis (FSGS) predominates. High-salt diet
      in heterozygous animals induces transition from benign to malignant phase of
      hypertension. In this case, ischemic glomerular changes are superimposed on
      preexisting secondary FSGS. In the regression model of hypertension (late-onset
      treatment) the effect of salt intake is attenuated. In homozygous TGR, early
      selective ET(A) receptor blockade decreased blood pressure and ameliorated end
      organ damage. Late selective ET(A) receptor blockade reduced podocyte injury
      despite final severe hypertension. Survival rate was markedly improved in both
      regimens with ET(A) selective blockade, while there was only partial improvement
      with early non-selective blockade. Both bosentan and atrasentan decreased ET-1
      levels in both regimens. In heterozygous TGR, early and late ET(A) treatment
      substantially while ET(A)/ET(B) treatment partially improved survival rate.
      Significant effect on BP was found with early and late ET(A) blockade, while
      ET(A)/ET(B) blockade had no effect. Bosentan and atrasentan similarly decreased
      ET-1 levels on both regimens. In conclusion, selective ET(A) receptor blockade is
      superior to nonselective ET(A)/ET(B) receptor blockade in attenuating
      hypertension and end-organ damage. Its effect is more pronounced when applied
      early in the life.

PMID- 20131939
TI  - Hypercapnia attenuates hypoxic pulmonary hypertension by inhibiting lung radical
      injury.
AB  - Chronic lung hypoxia results in hypoxic pulmonary hypertension. Concomitant
      chronic hypercapnia partly inhibits the effect of hypoxia on pulmonary
      vasculature. Adult male rats exposed to 3 weeks hypoxia (Fi(02)=0.1) combined
      with hypercapnia (Fi(C02)=0.04-0.05) had lower pulmonary arterial blood pressure,
      increased weight of the right heart ventricle, and less pronounced structural
      remodeling of the peripheral pulmonary arteries compared with rats exposed only
      to chronic hypoxia (Fi(02)=0.1). According to our hypothesis, hypoxic pulmonary
      hypertension is triggered by hypoxic injury to the walls of the peripheral
      pulmonary arteries. Hypercapnia inhibits release of both oxygen radicals and
      nitric oxide at the beginning of exposure to the hypoxic environment. The plasma
      concentration of nitrotyrosine, the marker of peroxynitrite activity, is lower in
      hypoxic rats exposed to hypercapnia than in those exposed to hypoxia alone.
      Hypercapnia blunts hypoxia-induced collagenolysis in the walls of prealveolar
      pulmonary arteries. We conclude that hypercapnia inhibits the development of
      hypoxic pulmonary hypertension by the inhibition of radical injury to the walls
      of peripheral pulmonary arteries.

PMID- 20131940
TI  - Regulation of fetoplacental vascular bed by hypoxia.
AB  - Important fetal and perinatal pathologies, especially intrauterine growth
      restriction (IUGR), are thought to stem from placental hypoxia-induced
      vasoconstriction of the fetoplacental vessels, leading to placental hypoperfusion
      and thus fetal undernutrition. However, the effects of hypoxia on the
      fetoplacental vessels have been surprisingly little studied. We review here
      available experimental data on acute hypoxic fetoplacental vasoconstriction
      (HFPV) and on chronic hypoxic elevation of fetoplacental vascular resistance. The
      mechanism of HFPV includes hypoxic inhibition of potassium channels in the plasma
      membrane of fetoplacental vascular smooth muscle and consequent membrane
      depolarization that activates voltage gated calcium channels. This in turn causes
      calcium influx and contractile apparatus activation. The mechanism of chronic
      hypoxic elevation of fetoplacental vascular resistance is virtually unknown
      except of signs of the involvement of morphological remodeling.

PMID- 20131941
TI  - Prague hereditary hypercholesterolemic (PHHC) rat - a model of polygenic
      hypercholesterolemia.
AB  - Prague hereditary hypercholesterolemic (PHHC) rat - rat strain crossbred from
      Wistar rats - is a model of hypercholesterolemia induced by dietary cholesterol.
      Importantly, no bile salts and/or antithyroid drugs need to be added to the diet
      together with cholesterol to induce hypercholesterolemia. PHHC rats have only
      modestly increased cholesterolemia when fed a standard chow and develop
      hypercholesterolemia exceeding 5 mmol/l on 2 % cholesterol diet. Most of the
      cholesterol in hypercholesterolemic PHHC rats is found in VLDL that become
      enriched with cholesterol (VLDL-C/VLDL-TG ratio > 1.0). Concurrently, both IDL
      and LDL concentrations rise without any increase in HDL. PHHC rats do not
      markedly differ from Wistar rats in the activities of enzymes involved in
      intravascular remodelation of lipoproteins (lipoprotein and hepatic lipases and
      lecithin:cholesterol acyltransferase), LDL catabolism, cholesterol turnover rate
      and absorption of dietary cholesterol. The feeding rats with cholesterol diet
      results in development of fatty liver in spite of suppression of cholesterol
      synthesis. However, even though cholesterolemia in PHHC rats is comparable to
      human hypercholesterolemia, the PHHC rats do not develop atherosclerosis even
      after 6 months on 2 % cholesterol diet. Importantly, the crossbreeding
      experiments documented that hypercholesterolemia of PHHC rats is polygenic. To
      identify the genes that may be involved in pathogenesis of hypercholesterolemia
      in this strain, the studies of microarray gene expression in the liver of PHHC
      rats are currently in progress.

PMID- 20131942
TI  - Early and intensive rehabilitation predicts good functional outcomes in patients
      admitted to the stroke intensive care unit.
AB  - PURPOSE: Earlier and more intense rehabilitation benefit stroke patients. Yet,
      studies have caution intensive therapy during acute brain injury. This study
      examined the rehabilitation commencement time and intensity as predictors of
      functional outcomes in acute stroke patients admitted to the stroke intensive
      care unit (ICU). METHOD: Sociodemographic, medical, rehabilitative and functional
      data were collected on 154 acute stroke patients. Regression analyses were used
      to identify predictors for the basic activities of daily living (Barthel Index,
      BI) and the walking ability at discharge. RESULT: Rehabilitation commencement
      time and intensity significantly predicted the BI score at discharge after
      adjusting for initial severity (National Institute of Health Stroke Scale, NIHSS)
      and age (p < 0.05). For the walking function at discharge, only the
      rehabilitation intensity was a significant predictor after adjusting for initial
      severity and age (p < 0.05). Furthermore, with increasing rehabilitation
      intensity, patients with severe stroke benefited more than those with moderate
      stroke. CONCLUSION: Rehabilitation commencement time and intensity, after
      adjusting for admission functional status and severity of stroke, remained to be
      important predictors of stroke functional outcomes. This study supported the
      recommendation to commence rehabilitation early and intensively and provided
      evidence that this claim can be extended to acute stroke patients admitted to an
      ICU.

PMID- 20131943
TI  - Do the self-concept and quality of life decrease in CP patients? Focussing on the
      predictors of self-concept and quality of life.
AB  - PURPOSE: To find out if the quality of life (QOL) and self-concept of the
      children with cerebral palsy (CP) was different from that of children without
      disability, to investigate predictive variables that could affect self-concept
      and QOL. METHODS: A total of 40 children with CP and 46 age-matched peers were
      included. The baseline characteristics including sex, type of CP, the level of
      disability according to Gross Motor Function Classification System (GMFCS) were
      recorded. Education levels of both children and parents, demographic features of
      parents, features of living area, usage of devices and associated impairments
      were filled out. Self-concept was measured using Piers-Harris Self-concept (PH)
      Scale. Quality of life was measured by Pediatric Quality of Life Inventory 4.0
      (PedsQL). The physical and psychosocial health subscale scores of PedsQL (P
      PedsQL and PS-PedsQL) were recorded. RESULTS: Significant differences in mean
      scores favouring the control group were found for PH scale, PedsQL scale (p <
      0.001). P-PedsQL and PS-PedsQL of the CP group were lower than the control group
      (p < 0.001). PS-PedsQL report was significant predictor of self-concept. The
      presence of incontinence and GMFCS level were significant predictors of PedsQL
      and PPedsQL, respectively. CONCLUSION: Self-concept and QOL of the CP children
      were lower than the children without CP. Presence of incontinence, self-concept
      rating and GMFCS level were important to predict domains of QOL.

PMID- 20131944
TI  - Development and validation of the Italian version of the Spinal Cord Independence
      Measure III.
AB  - PURPOSE: To provide a translation and cultural adaptation of the Spinal Cord
      Independence Measure version III scale for Italy (i-SCIM3) and to validate this
      version of the scale. METHOD: i-SCIM3 was developed involving a forward-backward
      translation and administered to patients with spinal cord lesions (SCL) admitted
      to two centers. Two raters for each center evaluated patients at admission and
      discharge. Psychometric testing included reliability by internal consistency
      (Cronbach's alpha) and test-retest reliability. The validity of i-SCIM3 was
      assessed by comparing it with the Italian version of Functional Independence
      Measure (FIM). RESULTS: One hundred three adult patients with SCL (84 males) with
      a mean age of 50.33+/-15.35 years were recruited. Seventy-four patients were
      paraplegic and 29 patients were tetraplegic. The median time elapsed between the
      two evaluations was 77.5 days (interquartile range, 53-144 days). Internal
      consistency, inter-rater reliability, and test-retest reliability were
      satisfactory overall, showing values higher than 0.90. The validity of i-SCIM3
      was confirmed by the close correlation with FIM results both at admission and
      discharge (r=0.91, p<0.01). The sensitivity to change of i-SCIM3 was similar to
      that of FIM. CONCLUSION: i-SCIM3 was found to be a consistent, reliable, and
      valid scale for use in the clinical setting. It is the first validated scale in
      Italian for patients with SCL.

PMID- 20131945
TI  - Spinal cord injury rehabilitation research: patient priorities, current
      deficiencies and potential directions.
AB  - Purpose. To highlight research priorities of people with spinal cord injury
      (SCI), outline the current state of rehabilitation research and suggest
      potentially fruitful avenues for future inquiry. Method. Commentary. Results.
      People with SCI identify pain, depression, fatigue, pressure sores, spasticity
      and the management of bladder and bowel as research priorities. Research reveals
      multiple interconnections between these secondary problems, all of which
      negatively impact quality of life (QOL). However, despite a substantial volume of
      existing research, significant gaps in knowledge remain, duplications of research
      effort are apparent and few interventions have an adequate evidence base. Issues
      concerning community participation - another research priority - have only
      recently attracted researchers' attention. Conclusions. This commentary contends
      that research should: focus on issues and outcomes of relevance and importance to
      people living with SCI; address the complexities of secondary conditions and
      their inter-relationships; appraise environmental barriers to participation in
      meaningful living; be designed to identify and inform effective and relevant
      interventions. Innovative approaches to research partnerships, mixed methods and
      exploring variables usually omitted from quantitative studies might enhance the
      likelihood that the complexity of issues facing people living with SCI will be
      identified and addressed. Moreover, a governing focus on achieving lives
      experienced as hopeful, purposeful, satisfying and meaningful could contribute to
      enhancing QOL outcomes following SCI.

PMID- 20131946
TI  - Alexithymia in respiratory rehabilitation.
AB  - PURPOSE: To date, there are no studies that have investigated the role of
      alexithymia in respiratory rehabilitation. We aimed to observe the prevalence of
      alexithymia in patients attending respiratory rehabilitation and to verify the
      presence of a difference between alexithymics and non-alexithymics responsiveness
      to the respiratory rehabilitation standard protocol. METHODS: A prospective
      cohort study evaluating the influence of alexithymia on functional recovery of in
      patients afferent to the Respiratory Rehabilitation Unit of IRCCS San Raffaele
      Pisana. Sixty patients were consecutively enrolled into the study and evaluated
      for alexithymia, anxiety and depression. Functional recovery was assessed with
      the six-minute walking test (6MWT). Prior and post-completion of this test
      dyspnoea, oxygen saturation and cardiac frequency were recorded. RESULTS:
      Alexithymia was not found to be significantly affecting the functional recovery
      of participants in respiratory rehabilitation. The distance walked at the 6MWT
      (6MWD) increased in both alexithymics and non-alexithymics (p(alexithymics) =
      0.014; p(non-alexithymics) < 0.0001). Dyspnoea strongly improved among non
      alexithymics, although a signal for improvement was also found in alexithymics
      (p(alexithymics) = 0.046; p(non-alexithymics) = 0.0001). CONCLUSIONS: These
      findings suggest that alexithymia did not have a significant impact on functional
      recovery of patients in respiratory rehabilitation.

PMID- 20131947
TI  - Validity, invariance and responsiveness of a self-report measure of functional
      limitations and disability in multiple sclerosis.
AB  - OBJECTIVE: This study examined the structural and external aspects of score
      validity for the abbreviated Late Life-Function and Disability Inventory (LL-FDI)
      as well as its longitudinal measurement invariance and responsiveness in
      individuals with multiple sclerosis (MS). METHODS: The sample included 292
      individuals with MS who completed a battery of questionnaires on two occasions
      separated by 6 months. The battery included the abbreviated LL-FDI along with
      measures of mobility disability; neurological impairments; symptoms of fatigue,
      anxiety, depression and pain; health status; and quality of life. The data were
      analysed using Analysis of Moment Structures (AMOS) and Statistical Package for
      the Social Sciences (SPSS), versions 16.0. RESULTS: Confirmatory factor analysis
      supported the structural validity and longitudinal measurement invariance of the
      disability and functional limitations components of the abbreviated LL-FDI.
      MANOVA and bivariate correlations supported the external aspects of score
      validity based on differences in mean scores as a function of clinical MS course
      (relapsing vs. progressive) and level of mobility disability (mild vs. moderate
      mobility disability) and associations with measures of neurological impairments,
      symptoms, health status and QOL, respectively. ANOVA established the
      responsiveness (i.e., sensitivity for reflecting clinically important differences
      in health status across time) of the functional limitations and disability
      components of the abbreviated LL-FDI for detecting changes in mobility disability
      across 6-months. CONCLUSION: Such findings provide a new option for the
      measurement of functional limitations and disability using the abbreviated LL-FDI
      in persons with MS.

PMID- 20131948
TI  - Astute observations in their analysis of modifying existing person--environment
      interaction theory in disability.
AB  - Jahiel and Scherer point out very astutely that time can be a baffling confounder
      in viewing disability, taxing our ability to meaningfully apply the International
      Classification of Function, Disability and Health (ICF) model to outcomes
      analysis. Their approach to segmenting person and environment is constructive.
      But distilling factors based upon an a priori self-determination of disability as
      part of the model may also undercut the validity of the larger construct. While
      the authors are to be applauded for their efforts to extend existing models of
      disability to address their current shortcomings, attention must also be given to
      important socio- or geo-political factors that may deserve more than a contextual
      discussion and their own place in this developing theory.

PMID- 20131949
TI  - Body alignment and postural muscle activity at quiet standing and anteroposterior
      stability limits in children with spastic diplegic cerebral palsy.
AB  - PURPOSE: We investigated body alignment and muscle activity at quiet standing and
      anteroposterior stability limits in children with spastic diplegic cerebral palsy
      (SDCP). METHOD: Body alignment and electromyographic (EMG) activity of ventral
      and dorsal lower limb muscles at three different standing positions were compared
      between seven children with SDCP (SDCP(group)) and seven controls [typically
      developing (TD(group))]. We also compared these measurements in a child with SDCP
      before and after a 3-week training in which the child leant forward and
      maintained the forward-leaning posture with the help of a physiotherapist who
      manually held her lower limbs fixed in position. RESULTS: In TD(group), EMG
      activity of the dorsal muscles increased at the extreme forward-leaning position,
      whereas that of the ventral muscles increased at the extreme backward-leaning
      position. In SDCP(group), such direction-specific increases were observed in
      lower leg muscles but not in thigh muscles. As a result of training, direction
      specific activity in the dorsal muscles improved, and crouch posture was also
      improved. CONCLUSIONS: Our findings suggest that children with SDCP have
      difficulty modulating muscle activity while standing and that the quadriceps
      plays a critical role in maintaining couch posture. In addition, crouch posture
      may be improved by the training which focuses on control of the dorsal muscles.

PMID- 20131950
TI  - Theory or theories? A commentary on 'Initial steps towards a theory and praxis of
      person-environment interaction in disability'.
AB  - PURPOSE: This article comments on the paper by Rene Jahiel and Marcia Joslyn
      Scherer elsewhere in this issue. METHODS: This article adds theoretical
      constructs. RESULTS: In commenting on their paper, this article makes four broad
      points. First, the sub-components identified by Drs. Jahiel and Scherer comprise
      critical factors of disability and the environment that must be taken into
      account when examining personal interactions with the environment. Second, as
      important as these factors are, operationalization of the model is hindered by a
      lack of mutual exclusivity between the sub-components both within and between the
      disability and environmental components. Third, power can be assessed in terms of
      the relative strength of individual functioning versus environmental functioning
      via a systematic appraisal of those elements essential to understanding the
      concept of accessibility. Finally, the demographic distinction between cohort and
      period trend analysis is an important consideration to take into account when
      assessing the time dimension, as the authors urge.

PMID- 20131951
TI  - Perceptions of disability among mothers of children with disability in
      Bangladesh: implications for rehabilitation service delivery.
AB  - BACKGROUND: Eighty-five percent of children with disabilities (CWD) live in
      developing countries, and <5% receive rehabilitation services. PURPOSE: To
      describe perceptions of disability among mothers of CWD in Bangladesh, and to
      explore how these perceptions influence the care sought for their CWD. METHODS.
      Descriptive qualitative research methods were employed. Eleven semi-structured
      interviews were conducted with mothers of CWD receiving services at a large
      pediatric rehabilitation facility in Bangladesh. Interviews were recorded and
      transcribed, and data were coded and analyzed to identify themes. RESULTS: Three
      primary categories of themes emerged: (1) mothers' perceptions of disability; (2)
      perceptions of treatment; and (3) expectations for the future of their CWD. The
      findings suggest that the family members, healthcare providers, and the
      rehabilitation setting have a considerable influence on mothers' perceptions.
      Study participants had adopted a biomedical understanding of disability and
      treatment, but reported that family elders continued to believe strongly in
      traditional explanations creating conflict regarding appropriate treatment
      approaches. Participants suggested that education and peer support networks
      provided in the rehabilitation setting played (or could play) a critical role in
      addressing these conflicts. CONCLUSION: Understanding mothers' perceptions of
      disability and treatment, and the myriad of factors that influence those
      perceptions, provides valuable knowledge to assist in planning and delivery of
      family centered rehabilitation services for CWD. Rehabilitation has a central
      role to play in assisting mothers' understanding of the nature of their
      children's disabilities and how they can be managed. Ultimately, such an
      understanding may translate into improved social and educational opportunities
      for CWD.

PMID- 20131952
TI  - Attitudes and perceptions towards disability and sexuality.
AB  - PURPOSE: To describe current societal perceptions and attitudes towards sexuality
      and disability and how social stigma differs between individuals living with
      visible and invisible disabilities. METHOD: A qualitative approach was used to
      explore attitudes and perceptions towards sexuality and disability. Focus groups
      were conducted with the following groups: service providers, people with visible
      disabilities, people with invisible disabilities and the general public. The
      focus group participants viewed 'Sexability' a documentary film on sexuality and
      disability to stimulate discussion midway through the session. RESULTS: Findings
      suggest that individuals with disabilities are commonly viewed as asexual due to
      a predominant heteronormative idea of sex and what is considered natural. A lack
      of information and education on sexuality and disability was felt to be a major
      contributing factors towards the stigma attached to disability and sexuality.
      CONCLUSIONS: Stigma can lead individuals to internalise concepts of asexuality
      and may negatively impact confidence, desire and ability to find a partner while
      distorting one's overall sexual self-concept. Societal attitudes and perceptions
      are driven by education and knowledge, if there is no exposure to sexuality and
      disability, it follows suit that society would have a narrow understanding of
      these issues. Further research should focus on how best to educate and inform all
      members of society.

PMID- 20131953
TI  - The Modified Rivermead Mobility Index: reliability and convergent validity in a
      mixed neurological population.
AB  - PURPOSE: To assess the inter-rater reliability, internal consistency and
      convergent validity of the Modified Rivermead Mobility Index (MRMI) in a mixed
      neurological population. METHOD: The MRMI was scored for 30 consecutive patients
      (mean age 54.5+/-15.6 years) by two individual testers. Reliability was examined
      using intraclass correlation coefficients (ICC3,1) and Bland and Altman plots;
      internal consistency reliability using Cronbach's alpha (alpha) and convergent
      validity using Spearman's correlation coefficient (rho) test to compare the MRMI
      to the 10-m walk test as a gold standard of mobility. As the majority of patients
      had bilateral deficits, the MRMI was measured and added independently for both
      sides. RESULTS: The inter-rater reliability was excellent: ICC (95%
      CI)=0.93(0.86, 0.96). The Bland and Altman plots contained most data points and
      there was perfect agreement between raters bilaterally in 27% of cases, with a
      difference of one point in 60% of cases on the left and 63% of cases on the
      right. Internal consistency was good at alpha=0.72 (Rater 1) and 0.80 (Rater 2).
      The Spearman rho between MRMI and the 10-m walk test was high at 0.86.
      CONCLUSIONS: The MRMI was shown to have high levels of reliability in a mixed
      neurological population but we recommend that its psychometric properties are
      further investigated to establish the true clinical utility of this measure.

PMID- 20131954
TI  - Postural stability in patients with ankylosing spondylitis.
AB  - PURPOSE: The aim of this study is to determine whether the postural changes in
      ankylosing spondylitis (AS) affected postural stability. METHOD: A total of 64
      patients with a diagnosis of AS and 50 healthy volunteers were included in the
      study. The patients were divided into two groups according to a tragus-to-wall
      distance<15 cm (Group I, n=30) and >or=15 cm (Group II, n=34). The control group
      (Group III) consisted of 50 healthy volunteers. The postural stability was
      evaluated with the Biodex Stability System (BSS). The results of Antero-Posterior
      Stability Index (APSI), Medio-Lateral Stability Index (MLSI) and Overall
      Stability Index (OSI) were evaluated. RESULTS: There were statistically
      significant differences between the three groups for OSI, APSI and MLSI. MLSI
      results were significantly different among patient groups. When Group II and the
      control group were compared, there were significant differences for OSI, APSI,
      and MLSI. Comparing Group I with the control group revealed a more significant
      difference for OSI, APSI, and MLSI. CONCLUSIONS: We have found that postural
      stability decreases in patients with AS in both the early and the late stages of
      the disease, but especially in the latter ones. This result may be thought to be
      related with increased kyphosis which is seen during the course of the disease.

PMID- 20131955
TI  - Immunomodulatory effects of polysaccharopeptide (PSP) in human PBMC through
      regulation of TRAF6/TLR immunosignal-transduction pathways.
AB  - CONTEXT: Polysaccharopeptide (PSP) was extracted from Coriolus versicolor, and
      has been proved to be a valuable adjuvant for the combination with chemotherapy
      or radiotherapy in the treatment of various cancers. OBJECTIVE: To understand the
      mechanism of PSP on immunomodulation, we examined gene expression and cytokine
      secretion associated with immunosignal-transduction signaling in human peripheral
      blood mononuclear cells (PBMCs). METHODS: cDNA microarray and cytokine antibody
      array were used to identify differential gene expression profiles and cytokines
      secretion of PBMCs in the presence or absence of PSP for 24 h. The expression of
      the key genes and proteins related to Toll-like receptor (TLR) signaling and its
      downstream pathway was determined by RT-PCR or Western blot. RESULTS: Compared
      with the control group, PSP up-regulated 22 genes expression (such as IFN-gamma,
      CXCL10, TLR4, TLR5) in 117 genes associated with TLR signaling. Twenty-three of
      genes (e.g., TLR9, TLR10, SARM1, TOLLIP) related with TLR signaling pathway were
      down-regulated in PBMCs under PSP treatments. Five of cytokines (GCSF, GM-CSF, IL
      1alpha, IL-6, IFN-gamma) were up-regulated more than 1.3 times by PSP. The mRNA
      levels of TRAM, TRIF, and TRAF6, which are the key molecules of TLR signaling
      pathway, were markedly increased (P < 0.05). Moreover, the protein level of TRAF6
      was also markedly increased (P < 0.01). CONCLUSIONS: PSP-regulated gene
      expression and cytokine secretion related to TLR signaling pathway in human
      PBMCs. Especially, TRAM-TRIF-TRAF6 subsignaling pathway of TLR may be one of the
      key associated signaling pathways in the immunomodulation of PSP.

PMID- 20131956
TI  - Modulating endochondral ossification of multipotent stromal cells for bone
      regeneration.
AB  - For years it has been recognized that engineering of large bone constructs will
      be feasible only if the hurdle of vascularization is overcome. Attempts to
      engineer bone tissue have predominantly focused on intramembranous (direct) bone
      formation. A relatively new and most likely more physiological approach in this
      line is endochondral bone formation, comprising an intermediate cartilaginous
      stage. Cartilage in nature is an avascular tissue and its cells are equipped to
      survive the poor oxygenation and nutritional conditions inherent to implanted
      tissues. Subsequent terminal differentiation (hypertrophy) of the chondrocytes
      initiates the formation of a mineralized matrix that will then be converted into
      bone. Through this mechanism, our long bones grow and most fractures heal through
      the process of secondary fracture healing. The feasibility of the attractive
      concept of endochondral bone tissue engineering has already been shown. Most
      emphasis has gone to the multipotent stromal cells because of their great
      potential for expansion and differentiation and immunoprivileged nature. This
      review will focus on the promises and current status of this new field. Further,
      potent modulators of endochondral bone tissue engineering, including oxygen
      tension and mechanical stimuli, will be discussed.

PMID- 20131957
TI  - Hyul-Tong-Ryung suppresses PMA-induced MMP-9 expression by inhibiting AP-1
      mediated gene expression via ERK 1/2 signaling pathway in MCF-7 human breast
      cancer cells.
AB  - Our previous study has demonstrated that the methanol extract of Hyul-Tong-Ryung
      (HM) specifically suppresses the phorbol 12-myristate 13-acetate (PMA)-induced
      matrix metalloproteinase-9 (MMP-9) production through the inhibition of MMP-9
      mRNA expression in MCF-7 human breast carcinoma cells. However, the molecular
      mechanisms involved in transcriptional suppression of MMP-9 by HM in PMA-induced
      MCF-7 cells are not known. In this study, we aimed to elucidate the molecular
      mechanisms involved in the inhibition of MMP-9 expression by HM in PMA-induced
      MCF-7 cells. The results of promoter assay and EMSA showed that HM specifically
      inhibits MMP-9 gene expression by blocking PMA-stimulated activation of activator
      protein-1 (AP-1). In addition, PMA-stimulated phosphorylation of extracellular
      signal regulated kinase 1/2 (ERK 1/2) was suppressed by HM treatment, whereas the
      phosphorylation of either c-Jun N-terminal kinase (JNK) or p38 mitogen-activated
      protein kinase (MAPK) was not affected. HM could inhibit the PMA-induced MMP-9
      expression through suppression of the transcriptional activity of MMP-9 gene in
      MCF-7 cells. These results indicate that HM inhibits PMA-induced MMP-9 expression
      by blocking the activation of activator protein-1 (AP-1) via extracellular signal
      regulated kinase 1/2 (ERK 1/2) signaling pathway.

PMID- 20131958
TI  - Statin loading in patients undergoing percutaneous coronary intervention for
      acute coronary syndromes: a new pleiotropic effect?
AB  - Intensive statin treatment has proved beneficial in patients with acute coronary
      syndromes. However, this benefit may apply only to those undergoing percutaneous
      coronary intervention (PCI). Loading, preloading or reloading with high dose(s)
      of a statin may decrease major adverse cardiac events, revascularization of both
      target and non-target vessels as well as myocardial necrosis after PCI. It seems
      that different actions of statins are responsible for their protective role in
      target vessel and non-target vessel revascularization procedures. This editorial
      discusses the results of statin loading trials and comments on the possible
      mechanisms involved.

PMID- 20131959
TI  - Integrated speech and phonological awareness intervention for pre-school children
      with Down syndrome.
AB  - BACKGROUND: Children with Down syndrome experience difficulty with both spoken
      and written language acquisition, however controlled intervention studies to
      improve these difficulties are rare and have typically focused on improving one
      language domain. AIMS: To investigate the effectiveness of an integrated
      intervention approach on the speech, letter knowledge, and phonological awareness
      development of ten pre-school children with Down syndrome aged between 4;4 and
      5;5. METHODS & PROCEDURES: A multiple single-subject design was used to evaluate
      treatment effectiveness. Baseline and intervention measures for speech and pre-
      and post-intervention measures for letter knowledge and phonological awareness
      were compared. The intervention comprised three components: a parent-implemented
      home programme; centre-based speech-language therapy sessions, and 'Learning
      through Computer' sessions with a total intervention time of 20 hours over 18
      weeks. Letter knowledge and phonological awareness activities were linked to each
      child's speech targets. OUTCOMES & RESULTS: Results indicated significant
      treatment effects on speech measures for all ten participants. Six of the ten
      participants showed increases on letter knowledge and nine showed increased
      awareness of initial phonemes in words but responses were not above binomial
      chance level (that is, 70% correct) for phonological awareness tasks. Individual
      results are presented and implications for parents and therapists are discussed.
      CONCLUSIONS AND IMPLICATIONS: The findings of this study suggest an intervention
      approach that integrates speech, letter knowledge, and phonological awareness
      targets is effective in remediating speech error patterns at the single-word
      level in young children with Down syndrome. Phonological awareness and letter
      knowledge appeared to be stimulated through the intervention, but significant
      improvement above chance levels on untrained phonological awareness tasks was not
      evident. Follow-up investigation is necessary to determine longer-term outcomes.

PMID- 20131960
TI  - Conversational behaviour of children with Developmental Language Delay and their
      caretakers.
AB  - BACKGROUND: A subset of children with Developmental Language Delay (DLD)
      encountered difficulties with the regulation of spoken discourse. In the
      conversations of caretakers with DLD children, several studies report
      difficulties with turn-taking, a proneness to use the non-verbal register, child
      and caretaker problems with topic management. Longitudinal research has yet to be
      conducted on the conversational behaviour of young DLD children and their
      caretakers. AIMS: The study investigates the development of style and structure
      of conversations between preschool-aged DLD children and their caretakers. METHOD
      & PROCEDURES: In a longitudinal design, language samples from twelve DLD children
      and six Normal Language-Acquiring (NLA) children and their caretakers were
      recorded in semi-structured play situations at two-month intervals across a
      period of 18 months. The children were between 2 and 3 years of age at the start
      of the study. OUTCOMES & RESULTS: The data show that the DLD children
      predominantly use restricted linguistic forms, non-verbal register and experience
      difficulties with turn-taking, topic initiation and topic maintenance. The
      conversational style of the caretakers in dialogue with their DLD children
      consistently showed more attention-gathering turns, formulaic corrections, self
      repetitions and re-introductions of topics when compared with the conversational
      style of caretakers in dialogue with their NLA children across the 18 months.
      CONCLUSIONS & IMPLICATIONS: Caretakers in DLD dyads appear to develop a less
      facilitative conversational style and a decrease of contingencies in initiations
      and responses over time. The result is little opportunity for the conversational
      and linguistic skills of the DLD children to develop. Parental guidance in the
      form of conversational training, child-adjusted register, contingent response
      behaviour and the provision of language materials which can help the child
      discover his or her role as a conversational partner and recognize the different
      perspectives of conversational partners is emphasized.

PMID- 20131961
TI  - Gender differences in health-related quality of life following total
      laryngectomy.
AB  - BACKGROUND: The impact of a total laryngectomy on an individual's life has
      primarily been measured from a male viewpoint reflecting the demographics of a
      diagnosis of laryngeal cancer. A small number of studies have looked specifically
      at females, but very few are comparison studies. Consequently, there is little
      consistent research regarding any potential gender differences. AIMS: To
      investigate whether there are gender differences in perceptions of health-related
      quality of life and functional abilities following total laryngectomy. METHODS &
      PROCEDURES: A total of 43 participants (22 males, 21 females), who had undergone
      a total laryngectomy procedure at least one year previously, took part in the
      study. They completed The European Organisation for Research and Treatment of
      Cancer Core Questionnaire Version 3.0 (EORTC QLQ-C30) in conjunction with the
      disease-specific Head & Neck Cancer Module (QLQ-H&N35). OUTCOMES & RESULTS: There
      were no significant differences between males and females on demographic and
      disease-related variables, except for the following: significantly more females
      lived alone and changed their employment status following surgery. Males had a
      significantly higher global health status/quality of life than females (p < 0.05)
      and significantly higher levels of physical (p = 0.01), emotional (p < 0.01),
      cognitive (p < 0.05) and social functioning (p < 0.05). After adjusting for
      differences in living arrangements and change in employment status, differences
      in emotional and social functioning remained significant. There was a general
      trend for females to have higher symptom/impairment levels and to report more
      treatment-related problems, but the majority of these differences were not
      significant. CONCLUSIONS & IMPLICATIONS: Following total laryngectomy, females
      appear to be worsely affected in aspects of quality of life than males. Emotional
      and social functioning are particularly vulnerable. The findings imply that
      rehabilitation programmes after total laryngectomy need to evaluate quality of
      life and address these specific areas in order to improve patient-reported long
      term outcomes.

PMID- 20131962
TI  - Beginning to teach the end: the importance of including discharge from aphasia
      therapy in the curriculum.
AB  - BACKGROUND: Discharging clients with long-term aphasia from therapy services
      constitutes a challenging dilemma for practising clinicians for a multitude of
      reasons. Although discharge was raised and discussed as a contentious issue in
      the field of aphasiology ten years ago, it remains an aspect of practice which is
      complex and underexplored. We are only a little more enlightened now than then on
      how to address this issue in relation to professional education and practice.
      AIMS: This paper draws on a single case study of a man with aphasia, his wife,
      and treating clinician, taken from a substantial research study, to highlight
      awareness of how communication, choice and differing perceptions of goals of
      therapy influence the experience of the discharge process. The case serves as the
      context for addressing a gap in the university curriculum around teaching about
      discharge practice in the context of long-term aphasia. METHODS & PROCEDURES:
      This paper describes how university and practice educators could include
      discharge issues in students' learning by teaching discharge in context,
      addressing it in formal university lessons as well as through work-based learning
      opportunities in clinical placements, and by scaffolding learning using graduated
      learning outcomes over the different stages of the students' programme. MAIN
      CONTRIBUTION: This paper provides practical suggestions to guide the inclusion of
      discharge in teaching about communication disorders generally, and specifically
      in relation to long-term aphasia. Discharge needs to be appreciated within the
      context of the entire intervention process, with good practice modelled in both
      university and workplace settings. We propose that it is learned in association
      with stages of decision-making, duty of care, documentation, goal setting,
      continuous therapy evaluation, clinical reasoning, professional communication
      with clients, ethical behaviour, and evidence-based practice. CONCLUSIONS &
      IMPLICATIONS: Bringing discharge practice from the realm of implicit knowledge to
      one that can be examined and discussed in an explicit manner should help reduce
      anxieties about discharge for new clinicians, help to clarify and improve the
      discharge approaches used by clinicians and lead to better discharge experiences
      for clients.

PMID- 20131963
TI  - Speech perception and phonological short-term memory capacity in language
      impairment: preliminary evidence from adolescents with specific language
      impairment (SLI) and autism spectrum disorders (ASD).
AB  - BACKGROUND: The cognitive bases of language impairment in specific language
      impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel
      non-word comparison task which manipulated phonological short-term memory (PSTM)
      and speech perception, both implicated in poor non-word repetition. AIMS: This
      study aimed to investigate the contributions of PSTM and speech perception in non
      word processing and whether individuals with SLI and ASD plus language impairment
      (ALI) show similar or different patterns of deficit in these cognitive processes.
      METHOD & PROCEDURES: Three groups of adolescents (aged 14-17 years), 14 with SLI,
      16 with ALI, and 17 age and non-verbal IQ matched typically developing (TD)
      controls, made speeded discriminations between non-word pairs. Stimuli varied in
      PSTM load (two- or four-syllables) and speech perception load (mismatches on a
      word-initial or word-medial segment). OUTCOMES & RESULTS: Reaction times showed
      effects of both non-word length and mismatch position and these factors
      interacted: four-syllable and word-initial mismatch stimuli resulted in the
      slowest decisions. Individuals with language impairment showed the same pattern
      of performance as those with typical development in the reaction time data. A
      marginal interaction between group and item length was driven by the SLI and ALI
      groups being less accurate with long items than short ones, a difference not
      found in the TD group. CONCLUSIONS & IMPLICATIONS: Non-word discrimination
      suggests that there are similarities and differences between adolescents with SLI
      and ALI and their TD peers. Reaction times appear to be affected by increasing
      PSTM and speech perception loads in a similar way. However, there was some,
      albeit weaker, evidence that adolescents with SLI and ALI are less accurate than
      TD individuals, with both showing an effect of PSTM load. This may indicate, at
      some level, the processing substrate supporting both PSTM and speech perception
      is intact in adolescents with SLI and ALI, but also in both there may be impaired
      access to PSTM resources.

PMID- 20131965
TI  - Dna2 on the road to Okazaki fragment processing and genome stability in
      eukaryotes.
AB  - DNA replication is a primary mechanism for maintaining genome integrity, but it
      serves this purpose best by cooperating with other proteins involved in DNA
      repair and recombination. Unlike leading strand synthesis, lagging strand
      synthesis has a greater risk of faulty replication for several reasons: First, a
      significant part of DNA is synthesized by polymerase alpha, which lacks a
      proofreading function. Second, a great number of Okazaki fragments are
      synthesized, processed and ligated per cell division. Third, the principal
      mechanism of Okazaki fragment processing is via generation of flaps, which have
      the potential to form a variety of structures in their sequence context. Finally,
      many proteins for the lagging strand interact with factors involved in repair and
      recombination. Thus, lagging strand DNA synthesis could be the best example of a
      converging place of both replication and repair proteins. To achieve the risky
      task with extraordinary fidelity, Okazaki fragment processing may depend on
      multiple layers of redundant, but connected pathways. An essential Dna2
      endonuclease/helicase plays a pivotal role in processing common structural
      intermediates that occur during diverse DNA metabolisms (e.g. lagging strand
      synthesis and telomere maintenance). Many roles of Dna2 suggest that the
      preemptive removal of long or structured flaps ultimately contributes to genome
      maintenance in eukaryotes. In this review, we describe the function of Dna2 in
      Okazaki fragment processing, and discuss its role in the maintenance of genome
      integrity with an emphasis on its functional interactions with other factors
      required for genome maintenance.

PMID- 20131966
TI  - Temporal and spatial mouse brain expression of cereblon, an ionic channel
      regulator involved in human intelligence.
AB  - A mild form of autosomal recessive, nonsyndromal intellectual disability (ARNSID)
      in humans is caused by a homozygous nonsense mutation in the cereblon gene
      (mutCRBN). Rodent crbn protein binds to the intracellular C-terminus of the large
      conductance Ca(2+)-activated K(+)channel (BK(Ca)). An mRNA variant (human SITE 2
      INSERT or mouse strex) of the BK(Ca) gene (KCNMA1) that is normally expressed
      during embryonic development is aberrantly expressed in mutCRBN human
      lymphoblastoid cell lines (LCLs) as compared to wild-type (wt) LCLs. The present
      study analyzes the temporal and spatial distribution of crbn and kcnma1 mRNAs in
      the mouse brain by the quantitative real-time reverse transcriptase-polymerase
      chain reaction (qPCR). The spatial expression pattern of endogenous and exogenous
      crbn proteins is characterized by immunostaining. The results show that
      neocortical (CTX) crbn and kcnma1 mRNA expression increases from embryonic stages
      to adulthood. The strex mRNA variant is >3.5-fold higher in embryos and decreases
      rapidly postnatally. Mouse crbn mRNA is abundant in the cerebellum (CRBM), with
      less expression in the CTX, hippocampus (HC), and striatum (Str) in adult mice.
      The intracytoplasmic distribution of endogenous crbn protein in the mouse CRBM,
      CTX, HC, and Str is similar to the immunostaining pattern described previously
      for the BK(Ca) channel. Exogenous hemagglutinin (HA) epitope-tagged human wt- and
      mutCRBN proteins using cDNA transfection in HEK293T cell lines showed the same
      intracellular expression distribution as endogenous mouse crbn protein. The
      results suggest that mutCRBN may cause ARNSID by disrupting the developmental
      regulation of BK(Ca) in brain regions that are critical for memory and learning.

PMID- 20131967
TI  - Transplacental traffic after in utero mesenchymal stem cell transplantation.
AB  - Transplacental traffic of fetal progenitor and differentiated cells is a well
      known phenomenon in pregnancies. We hypothesize that intrauterine stem cell
      transplantation leads to microchimerism in the dams and that this is gestational
      age-dependent. EGFP+ fetal liver-derived mesenchymal stem cell (MSC) (10(5) per
      fetus) were injected intraperitoneally into congeneic and allogeneic recipient
      fetuses at E12 versus E13.5 of murine pregnancy (56 dams). Engraftment in
      maternal organs was evaluated using TaqMan quantitative polymerase chain reaction
      (PCR) and fluorescence microscopy during pregnancy (1, 3, and 7 days after in
      utero transplantation [IUT]) and after delivery (1 and 4 weeks after delivery).
      One day after IUT donor cells were mainly found in the placenta (E12: 9/10 dams
      vs. E13.5: 4/8 dams) and laparotomy site (E12: 5/10 dams vs. E13.5: 4/8 dams).
      Three days after IUT these probabilities decreased significantly in the placenta
      to 3/8 and 1/3, respectively, whereas it was increased within the surgical wound
      to 8/8 and 2/4. One week after IUT donor cells could be detected in other single
      maternal organs, such as bone marrow or spleen. The surgical wound was chimeric
      in all dams. One week after delivery the surgical wound was still a major site of
      engraftment in both groups. E12 IUT resulted in detectable donor cell
      microchimerism in the maternal bone marrow (3/4), liver (2/4), lungs (1/4),
      spleen (1/4), and thymus (1/4), whereas engraftment probabilities were lower
      following E13.5 IUT (BM: 1/4, liver: 2/4, lungs: 1/4, spleen: 1/4, thymus: 0/4).
      At 4 weeks after delivery persistent microchimerism was found only after E12 IUT
      in various maternal organs (BM: 1/4, spleen: 1/4, lungs: 1/4) and within newly
      created surgical wounds (3/4), but completely not in the E13.5 group. Allogeneic
      IUT did also not result in any detectable long-term fetal microchimerism. An
      earlier IUT might lead to a higher transplacental traffic of donor MSC and
      persistent microchimerism within maternal tissues. Even 4 weeks after delivery,
      these cells are present in surgical wounds.

PMID- 20131968
TI  - Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers
      for malignant mesothelioma: analytical validation of ELISA based assays and
      characterization at mRNA and protein levels.
AB  - BACKGROUND: There is a need to identify reliable markers for malignant
      mesothelioma. Soluble mesothelin related peptides (SMRP) and osteopontin (OPN)
      have gained interest in recent years for this purpose. METHODS: SMRP (Fujirebio
      Diagnostics Inc.) and OPN (R&D Inc.) ELISA methods were evaluated for multiple
      parameters. Concentrations were measured in blood from patients with
      mesothelioma, normal healthy volunteers, and patients with other (non
      mesothelioma) cancers. In silico analysis was performed using the GeoProfiles
      database. At the protein level, SMRP and OPN were measured in cell culture
      supernatants, and values were compared in patients pre- and post-extrapleural
      pneumonectomy. RESULTS: The SMRP assay demonstrates intra-assay CVs of 2.3% and
      3% (at 4.6 nM and 13.7 nM, respectively), and inter-assay CVs of 3.5% and 3.7% at
      the same concentrations. The limit of detection (LOD) is 0.182 nM. The OPN assay
      demonstrates intra-assay CVs of 5.8%, 4.1%, and 5.2% (at 1.9, 5.1, and 11.1
      ng/mL, respectively), and inter-assay CVs of 8.5%, 8.4%, and 12.1% at the same
      concentrations. The LOD is 0.032 ng/mL. Both SMRP and OPN in mesothelioma
      patients were significantly higher than in patients with other (non-mesothelioma)
      cancer and in healthy volunteers. The two markers do not appear to correlate with
      each other and exhibit different tissue expression patterns. Protein
      concentrations of these markers are highest in different sets of cell lines.
      Finally, SMRP but not OPN concentrations were decreased in five of seven
      consecutive patients after extrapleural pneumonectomy, compared to their
      respective pre-operative values. CONCLUSIONS: These assays provide reliable and
      reproducible quantitation of SMRP and OPN proteins. Both are increased in
      mesothelioma patients compared to non-mesothelioma controls. However, the two
      analytes do not correlate with each other and show distinct expression profiles
      and protein expression. Concentrations of SMRP but not OPN are decreased in post
      surgical samples. Our results further characterize these markers, establish assay
      performance characteristics, and lay the groundwork for further studies to
      measure these markers in blood.

PMID- 20131969
TI  - Comparison of the Vitek 2 system with the CLSI broth microdilution, disk
      diffusion, and sterol quantitation methods for determining fluconazole
      susceptibility against Candida spp.

PMID- 20131970
TI  - Teratogenic potential in cultures optimized for oligodendrocyte development from
      mouse embryonic stem cells.
AB  - We describe a rapid and efficient 5-step program of defined factors for the
      genesis of brain myelin-forming oligodendrocytes (OLs) from embryonic stem cells
      (ESCs). The OLs emerge on the same time frame in vitro as seen in vivo. Factors
      promoting neural induction (retinoids, noggin) are required, while exogenous
      Sonic hedgehog is not. In contrast we were unable to generate OLs by trans
      differentiation of ethically neutral mesenchymal stem cells, indicating a
      requirement for cis-differentiation via neural ectoderm for OL genesis. In the
      ESC-derived cultures, our optimized protocol generated a mixed population with
      49% O4(+), Olig2(+) OL lineage cells. These cultures also retained pluripotential
      markers including Oct4, and an analysis of embryoid body formation in vitro, and
      allogeneic grafts in vivo, revealed that the ESC-derived cultures also retained
      teratogenic cells. The frequency of embryoid body formation from terminal
      differentiated OL cultures was 0.001%, 100-fold lower than that from ESCs. Our
      results provide the first quantitative measurement of teratogenicity in ESC
      derived, exhaustively differentiated allogeneic grafts, and demonstrate the
      unequivocal need to purify ESC-derived cells in order to generate a safe
      population for regenerative therapy.

PMID- 20131971
TI  - Upper limb neurorehabilitation in patients with stroke using haptic device
      system: reciprocal bi-articular muscle activities reflect as a result of improved
      circle-drawing smoothness.
AB  - PURPOSE: Muscular co-contraction resulted in corrected elbow and shoulder joint
      stiffness; however, this correction neither ameliorated endpoint oscillation nor
      assisted in the execution of smooth two-joint arm movements. We hypothesised that
      the reacquisition of smooth arm movements became synonymous with the restoration
      of time-domain reciprocal electromyographic (EMG) activities in biarticular arm
      muscles. The purpose of this study was to investigate whether or not the restored
      reciprocal EMG activities in biarticular arm muscles reflected improved smooth
      motor performance in patients with stroke after 10 days of two-joint arm-movement
      training. METHODS: Three male patients with sub-acute stroke with left-arm
      paralysis performed circle-drawing tasks using a haptic device system for upper
      limb neuromuscular rehabilitation. RESULTS: After the training, the movement
      velocities and achievement periods increased with the enhancement of the
      reciprocal EMG activities in biarticular arm muscles, and there was less jerkness
      in movement after training for the same duration. CONCLUSIONS: Patients with
      stroke could achieve smooth motor performance with the restoration of the
      reciprocal EMG activities in biarticular arm muscles. Therefore, the reciprocal
      EMG activities in biarticular arm muscles in response to circle drawing would be
      an index for the progressive improvements of smooth motor functions in the upper
      limbs.

PMID- 20131972
TI  - Relationship between wheelchair durability and wheelchair type and years of test.
AB  - OBJECTIVE: To investigate the relationship between the durability of wheelchairs
      according to American National Standard for Wheechairs/Rehabilitation Engineering
      and Assistive Technology Society of North America (ANSI/RESNA) Wheelchair
      Standards and wheelchair type as well as year of test. DESIGN: A retrospective
      study design with a sample of 246 wheelchairs that were tested in accordance with
      the ANSI/RESNA standards from 1992 to 2008 including four types of wheelchairs:
      manual wheelchair (MWC), electrical powered wheelchair (EPW), scooters and
      pushrim-activated power-assisted wheelchair (PAPAW). Unconditional binary logic
      regression analysis was chosen to evaluate the relationship between test results
      and test year as well as wheelchair type. SETTING: Rehabilitation Engineering
      Research Center. MAIN OUTCOME MEASURES: Wheelchair durability test result
      (fatigue test: pass or fail) RESULTS: There was no significant correlation
      between the year when tested and equivalent cycles. A significant relation was
      found between test results and wheelchair type (Wald score = 10.845, degree of
      freedom = 3, p = 0.013) with scooters having a significantly higher pass ratio
      than MWC (OR = 15.629, 95% CI = 2.026-120.579). EPW also had significantly higher
      pass ratio than MWC (OR = 1.953, 95% CI = 1.049-3.636). No significant difference
      on pass ratio was found between PAPAW and MWC. CONCLUSIONS: No significant
      improvements in wheelchair test results during the time frame from 1992 to 2008
      were discovered. Wheelchair standard tests should be conducted to assure minimum
      quality of the wheelchairs and for improving the design of wheelchairs. Although
      the ANSI/RESNA wheelchair durability test procedures have remained consistent, it
      does not appear that the introduction of new materials, designs and the
      availability of test data have improved wheelchair fatigue life.

PMID- 20131973
TI  - Designing reasonable accommodation of the workplace: a new methodology based on
      risk assessment.
AB  - If working tasks are carried out in inadequate conditions, workers with
      functional limitations may, over time, risk developing further disabilities.
      While several validated risk assessment methods exist for able-bodied workers,
      few studies have been carried out for workers with disabilities. This article,
      which reports the findings of a Study funded by the Italian Ministry of Labour,
      proposes a general methodology for the technical and organisational re-design of
      a worksite, based on risk assessment and irrespective of any worker disability.
      To this end, a sample of 16 disabled workers, composed of people with either mild
      or severe motor disabilities, was recruited. Their jobs include business
      administration (5), computer programmer (1), housewife (1), mechanical worker
      (2), textile worker (1), bus driver (1), nurse (2), electrical worker (1),
      teacher (1), warehouseman (1). By using a mix of risk assessment methods and the
      International Classification of Functioning (ICF) taxonomy, their worksites were
      re-designed in view of a reasonable accommodation, and prospective evaluation was
      carried out to check whether the new design would eliminate the risks. In one
      case - a man with congenital malformations who works as a help-desk operator for
      technical assistance in the Information and Communication Technology (ICT)
      department of a big organisation - the accommodation was actually carried out
      within the time span of the study, thus making it possible to confirm the
      hypotheses raised in the prospective assessment.

PMID- 20131974
TI  - Manual wheelchair propulsion pattern use by people with multiple sclerosis.
AB  - PURPOSE: To determine the most commonly used manual wheelchair propulsion pattern
      by people with multiple sclerosis (MS) and to assess which factors influence the
      preference. METHOD: Sixty manual wheelchair users with MS from an MS outpatient
      rehabilitation centre in Northern Italy were assessed on upper limb range of
      motion and trunk stability to determine if these factors or demographic, disease
      or wheelchair use history, influenced the choice of wheelchair propulsion
      pattern. RESULTS: Fifty-four (90%) subjects used the arcing propulsion pattern,
      the least efficient pattern as reported in the literature. Sixteen (26.7%)
      subjects had impaired trunk stability and 38 (63.3%) subjects demonstrated some
      deficit on either extremity for active range flexion-extension. Twenty (33%)
      subjects had no deficits on active range flexion-extension and had normal trunk
      control. Upper limb range of motion and trunk stability were not significant in
      determining the preference for propulsion pattern (p = 1.05 and 0.38,
      respectively). Demographic and disease factors and wheelchair use history were
      also not significant in determining propulsion pattern. CONCLUSIONS: The person
      with MS uses the least efficient pattern overall, requiring frequent repetition,
      although a smaller range of movement. This may be an energy conservation
      technique that helps in managing fatigue.

PMID- 20131975
TI  - Injury risk compensation in children with disabilities: could assistive
      technology devices have a dark side?
AB  - PURPOSE: This review article investigates the role of assistive technology (AT)
      devices and other contextual aspects as unintentional injury risk factors in
      children with disabilities. METHOD: A literature review was conducted to identify
      and review empirical studies that examined the role of AT devices, protective
      equipment (PE), and other consumer products in the risk-taking behaviors of
      children and their parents. RESULTS: Nine original empirical studies and one
      systematic review examining changes in the risk-taking behaviors or injury levels
      associated with children's PE and other products were identified and critically
      reviewed. None of the articles specifically addressed the compensatory effect of
      AT devices. Since evidence of changes in the risk tolerance of children and their
      parents after the introduction of PE and other products for children exists, it
      is conceivable under certain conditions that AT devices could interact with other
      known risk factors to promote injury risk-taking behaviors in children and their
      parents. CONCLUSIONS: Outcomes of this review and current thinking about the
      interaction of health conditions and contextual factors provide a theoretical
      underpinning to explore the causal association among unintentional injury risk
      factors and AT device use by children with disabilities.

PMID- 20131976
TI  - Mobility-related participation and user satisfaction: construct validity in the
      context of powered wheelchair use.
AB  - PURPOSE: The aim of this study was to investigate the constructs of mobility
      related participation and user satisfaction, two important outcome dimensions
      within praxis and research on mobility device interventions. METHOD: To fulfill
      this aim, validity and reliability of a 12-item scale on mobility-related
      participation and a 10-item scale on user satisfaction were examined in the
      context of older people's powered wheelchair use (n = 111). Rasch analysis and
      correlation analysis were applied. RESULTS: Construct validity of both scales was
      confirmed. The reliability of the user satisfaction scale was good, while the
      mobility-related participation scale was not optimal in discriminating between
      persons with a high degree of mobility-related participation. It was demonstrated
      that mobility-related participation and user satisfaction are separate, not
      related constructs. CONCLUSIONS: It can be concluded that the investigated
      mobility-related participation and user satisfaction constructs appear to be
      valid. Since the two constructs are not related and both yield important
      information, both dimensions should be evaluated in outcomes research and praxis
      targeting powered wheelchair interventions. Reliability problems of the mobility
      related participation scale indicate the complexity of this construct. The
      results have been instrumental in the development of a new scale for measuring
      mobility-related participation 'The NOMO 1.0'.

PMID- 20131977
TI  - Are wheelchair-skills assessment and training relevant for long-standing
      wheelchair users? Two case reports.
AB  - PURPOSE: We present two case reports that shed light on the question of whether
      routine periodic wheelchair-skills assessment and training are relevant for long
      standing wheelchair users. CASE 1: A 60-year-old man with a 15-year history of
      T12 complete paraplegia sustained an intertrochanteric fracture of his femur due
      to a tip-over accident that occurred 2 days after a follow-up clinic visit at
      which no limitations in wheelchair-skill performance were identified. If a
      procedure had been in place to identify and correct his wheelchair-skill
      deficiencies, this injury might have been prevented. CASE 2: A 34-year-old woman
      with spina bifida, whose wheelchair use had gradually increased, came to our
      attention during the provision of a new wheelchair. She was able to significantly
      improve her wheelchair abilities through training. The newly learned skills
      enhanced her community participation. CONCLUSIONS: These cases suggest that, even
      in long-standing wheelchair users, wheelchair skills should be routinely assessed
      as part of the periodic functional assessment and, when the skill level is
      determined to be less than appropriate for that person, formal training should be
      offered.

PMID- 20131978
TI  - Bedside computer access for an individual with severe and multiple disabilities:
      a case study.
AB  - PURPOSE: This case study documents the process of designing a custom-tailored
      bedside computer access solution for a 20-year old individual with quadriplegia
      and reports the effects of computer access on her participation in life
      activities. METHOD: We adopted a person-focused approach to match the individual
      to an access solution. Two months after the access solution's introduction, we
      measured its impact using a 2-dimensional Fitt's Law test and questionnaire from
      the ISO 9241-9 standards document, typing tests, a usage log and a semi
      structured interview. The Canadian Occupational Performance Measure was also
      administered pre- and post- access, focusing on the client's perceived ability to
      use the computer. RESULTS: After 2 months, the individual was spending an average
      of 8.4 h per day on the computer, engaging in electronic communication,
      recreational, and educational activities. She learned single-switch typing with a
      throughput of 1.03 bits/s and targeting accuracy of 87.5%. The questionnaire
      revealed that the client was thoroughly satisfied with the interface. These
      results were interpreted as positive gains in the International Classification of
      Functioning, Disability and Health domains of communication and social
      interaction. CONCLUSIONS: By addressing individual goals, abilities and relevant
      environmental factors, a bedside computer access solution can be developed for
      individuals in long-term care. The introduction of a computer access solution
      augmented the participant's communication, leisure and educational activities, as
      well as perceived independence.

PMID- 20131979
TI  - Stem cells from human-exfoliated deciduous teeth can differentiate into
      dopaminergic neuron-like cells.
AB  - Stem cells from human exfoliated deciduous teeth (SHED) have been identified as a
      novel population of postnatal stem cells capable of differentiating into neural
      cells, odontogenic cells, and adipocytes. SHED were reported to differentiate
      into neural cells based on cellular morphology and the expression of early
      neuronal markers when cultured under neural inductive conditions. This study
      therefore investigated the therapeutic efficacy of SHED in alleviating
      Parkinson's disease (PD) in a rat model. We found that SHED could be induced to
      form neural-like spheres in a medium optimized for neural stem cells in vitro.
      After incubation with a cocktail of cytokines including sonic hedgehog,
      fibroblast growth factor 8, glial cell line-derived neurotrophic factor, and
      forskolin, these SHED-derived spheres further differentiated into a cell
      population that contained specific dopaminergic neurons. Moreover,
      transplantation of SHED spheres into the striatum of parkinsonian rats partially
      improved the apomorphine-evoked rotation of behavorial disorders compared to
      transplantation of control SHED. Our data indicate that SHED, potentially derived
      from neural crest cells, may be an optimal source of postnatal stem cells for PD
      treatment.

PMID- 20131980
TI  - Clobetasol propionate shampoo 0.05% is efficacious and safe for long-term control
      of moderate scalp psoriasis.
AB  - We evaluated in this study the efficacy and safety of an alternate regimen using
      clobetasol propionate 0.05% shampoo (CP shampoo) for long-term control of scalp
      psoriasis. Patients with moderate scalp psoriasis (Global Severity Score [GSS] of
      3 on a 0-5 scale) first received CP shampoo once daily for 4 weeks. Patients with
      a GSS <or= 2 were then randomized into the maintenance phase, receiving CP
      shampoo or vehicle twice weekly. When relapse (GSS > 2) occurred, patients
      received the 4-week daily CP shampoo treatment. Patients who had a GSS <or= 2
      afterwards reinitiated the twice-weekly maintenance according to the original
      randomization scheme. Among the 168 patients enrolled, 141 (83.9%) had a GSS <or=
      2 after the initial phase. The median time to first relapse was 141 days with CP
      shampoo, almost 4 months later than with vehicle (30.5 days;p < 0.0001). After 6
      months, the percentage of patients who had no relapse was significantly higher
      with CP shampoo (40.3%) than with vehicle (11.6%;p < 0.001). CP shampoo was also
      safe during the 7-month study period, without leading to more cases of skin
      atrophy, telangiectasia, hypothalamic-pituitary-adrenal (HPA) axis suppression or
      adverse events compared to vehicle. The alternate treatment regimen with CP
      shampoo is efficacious and safe for long-term management of moderate scalp
      psoriasis.

PMID- 20131981
TI  - Lipid nanoparticles loaded with 10-hydroxycamptothecin-phospholipid complex
      developed for the treatment of hepatoma in clinical application.
AB  - For the purpose of clinical intravenous injection of 10-hydroxycamptothecin, a
      novel formulation of lipid nanoparticles loaded with 10-hydroxycamptothecin
      phospholipid complex (HCPT-PC-LNs) was prepared by solvent evaporation and high
      pressure homogenization methods. Spherical particles with a mean particle size of
      200 nm and high encapsulation efficiency of 97.39 +/- 0.91% could be achieved
      under optimal conditions. In vitro release profile showed that the release
      pattern of HCPT from nanoparticles was retarded with neglectable initial burst
      release and well-fitted to Ritger-Peppas equation. In vivo distribution studies
      in mice showed that HCPT-PC-LNs were mainly localized in liver. Besides, in situ
      mouse hepatoma model was established and tumor uptake of HCPT-PC-LNs was much
      higher than that of free HCPT (more than 18-fold). It was found that HCPT-PC-LNs
      exhibited high growth inhibitory effect on human liver cancer cells by MTT assay.
      The cellular uptake of HCPT was 24.33 +/- 1.30 x 10(-7) microg/cell in HCPT-PC
      LNs treated group at 12 h, which was almost 14-fold higher than that of free HCPT
      (1.72 +/- 0.57 x 10(-7) microg/cell). This study suggested that the HCPT-PC-LNs
      could be utilized as a novel formulation for liver tumors therapy, which might be
      applied in clinic in the near future.

PMID- 20131982
TI  - Synthesis of Ag-liposome nano composites.
AB  - Silver nanoparticles were synthesized and stabilized by a simple, environment
      friendly method in a liposomes structure. Liposomes were prepared by facing
      lecithin to the aqueous-phase solutions while stirring vigorously. The ratio of
      lecithin concentration to silver nitrate (K(Lec/Ag) = [Lecithin]/[AgNO(3)]) is
      the influencing factor in the synthesis of silver nanoparticles. The stability,
      size distribution, and antibacterial properties of synthesized silver
      nanoparticles were studied by ultraviolet (UV)-visible, dynamic light scattering,
      and antibacterial assay. The UV spectra indicated a single symmetric extinction
      peak at 400 nm, confirming the spherical shape of the synthesized silver
      nanoparticles. A high K(Lec/Ag) value leads to a reduction in the intensity of
      extinction spectra and increases the size of Ag-liposomes nanocomposites. The
      large Ag-liposomes nanocomposites are transformed to the smaller Ag-liposomes
      nanocomposites (from 342 to 190 nm) due to sonication treatment. The stabilized
      silver nanoparticles with various lecithin concentrations showed a good
      antibacterial activity against Staphylococcus aureus, a Gram-positive bacterium,
      and Escherichia coli, a Gram-negative bacterium.

PMID- 20131983
TI  - Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products
      (OIPs): Workshop Summary Report.
AB  - This March 2009 Workshop Summary Report was sponsored by Product Quality Research
      Institute (PQRI) based on a proposal by the Inhalation and Nasal Technology Focus
      Group (INTFG) of the American Association of Pharmaceutical Scientists (AAPS).
      Participants from the pharmaceutical industry, academia and regulatory bodies
      from the United States, Europe, India, and Brazil attended the workshop with the
      objective of presenting, reviewing, and discussing recommendations for
      demonstrating bioequivalence (BE) that may be considered in the development of
      orally inhaled drug products and regulatory guidances for new drug applications
      (NDAs), abbreviated NDAs (ANDAs), and postapproval changes. The workshop
      addressed areas related to in vitro approaches to demonstrating BE, biomarker
      strategies, imaging techniques, in vivo approaches to establishing local delivery
      equivalence and device design similarity. The workshop presented material that
      provided a baseline for the current understanding of orally inhaled drug products
      (OIPs) and identified gaps in knowledge and consensus that, if answered, might
      allow the design of a robust, streamlined method for the BE assessment of locally
      acting inhalation drugs. These included the following: (1) cascade impactor (CI)
      studies are not a good 2 predictor of the pulmonary dose; more detailed studies
      on in vitro/in vivo correlations (e.g., suitability of CI studies for assessing
      differences in the regional deposition) are needed; (2) there is a lack of
      consensus on the appropriate statistical methods for assessing in vitro results;
      (3) fully validated and standardized imaging methods, while capable of providing
      information on pulmonary dose and regional deposition, might not be applicable to
      the BE of inhaled products mainly due to the problems of having access to
      radiolabeled innovator product; (4) if alternatives to current methods for
      establishing local delivery BE of OIPs cannot be established, biomarkers
      (pharmacodynamic or clinical endpoints) with a sufficiently steep dose-response
      need to be identified and validated for all relevant drug classes; and (5) the
      utility of pharmacokinetic studies for evaluating "local pulmonary delivery"
      equivalence deserves more attention. A summary of action items for seminars and
      working groups to address these topics in the future is also presented.

PMID- 20131984
TI  - Evaluation of lung tolerance of ethanol, propylene glycol, and sorbitan
      monooleate as solvents in medical aerosols.
AB  - BACKGROUND: Aerosol therapy is an expanding technique allowing administration of
      drugs acting locally in the bronchial tree and lungs or acting systemically after
      absorption through the respiratory tract. However, the choice of solvents and
      adjuvants is a critical step in the formulation process of new drugs. Pulmonary
      tolerance of ethanol, propylene glycol and sorbitan ester was evaluated in a rat
      model of intratracheal administration using a Microsprayer in a 4-day toxicity
      study. METHODS: Four groups of Sprague-Dawley rats (11 rats per group, n = 44)
      have received, on 4 consecutive days 150 microL of solutions containing the
      solvents, by intratracheal route using a IA-1B-2 inches-Microsprayer
      (PennCentury, Philadelphia, PA). Once a day, the rats received deionized water
      (control) or ethanol 10% or propylene glycol 30% or sorbitan monooleate 10%. All
      rats were sacrificed 24 h after the fourth administration. Biochemical analysis
      on bronchoalveolar lavage (BAL) fluid was performed on seven rats per group. The
      respiratory tract of the remaining four rats/group was examined histologically.
      RESULTS: Biochemistry and histopathology findings demonstrated that under the
      conditions tested, deionized water, 10% ethanol, and 30% propylene glycol were
      tolerated in a qualitatively similar way presenting limited cellular reaction. In
      contrast, 10% sorbitan monooleate produced an accumulation of foamy macrophages
      in the lungs and a higher degree of inflammation. In addition, animals in this
      group showed higher polymorphonuclear neutrophil recruitment and total proteins
      levels in BAL fluid. CONCLUSION: The overall results recommended ranking the
      vehicles according to the degree of inflammation which was induced: deionized
      water <10% ethanol < or =30% propylene glycol <10% Tween 80.

PMID- 20131985
TI  - A spatial model of the human airway tree: the hybrid conceptual model.
AB  - BACKGROUND: The conceptual model of the lung describes the spatial distribution
      of the air volume of each airway generation within the lung. It is a generic
      model that can be used as a powerful tool in interpreting images of aerosol
      deposition. The model divides the lung volume into 10 concentric shells, and
      specifies the volume of each airway generation in each shell based on a
      statistical analysis of morphometric data available in the literature. In this
      study, an updated version of the conceptual model, called the Hybrid Conceptual
      Model (HCM), is introduced. This model incorporates individual morphometric data
      from upper bronchial airways (generations 0-5) available from High Resolution
      Computed Tomography (HRCT). METHODS: The HCM has been tested on one 27-year-old
      healthy male volunteer, on which magnetic resonance imaging (MRI) and HRCT scans
      of the thorax have been performed. Four major changes have been introduced in the
      HCM; (1) the incorporation of in vivo data, (2) a better distribution of airway
      volume within each shell, (3) the adoption of more accurate morphometric
      assumptions, and (4) the incorporation of the spatial definition of the segmental
      divisions of the lung. RESULTS AND CONCLUSIONS: The resulting model was shown to
      compare very well to past literature models with respect to airway volume per
      generation and mean airway position within the lung. It can be concluded that the
      HCM can be used to describe the spatial location of different airway generations
      of the lung with good spatial and quantitative accuracy. This represents a
      further step toward the personalization of the conceptual model to an individual
      subject.

PMID- 20131986
TI  - USA's healthcare reform: why it will not work.

PMID- 20131987
TI  - From tumor size and HER2 status to systems oncology for very early breast cancer
      treatment.

PMID- 20131988
TI  - Breast cancer cell dormancy in bone marrow: potential therapeutic targets within
      the marrow microenvironment.

PMID- 20131990
TI  - Palonosetron hydrochloride for the prevention of chemotherapy-induced nausea and
      vomiting.
AB  - A large number of different 5-hydroxytryptamine (HT)(3) receptor antagonists have
      been marketed with the indication of preventing nausea and vomiting induced by
      chemotherapy--palonosetron is the most recently developed of these. Pharmacologic
      studies have revealed that palonosetron has a long half-life, a high affinity for
      5-HT(3) receptors, exhibits allosteric binding to 5-HT(3) receptors and possess
      positive cooperativity. Although interesting, pharmacologic differences are only
      useful if they result in clinical advantages, such as an increase in efficacy
      and/or an improvement in tolerability. We summarize preclinical and clinical
      studies of palonosetron and compare the efficacy and tolerability with the other
      5-HT(3) receptor antagonists, ondansetron, granisetron and dolasetron.

PMID- 20131991
TI  - Highlights of the Chemotherapy Foundation Symposium XXVII: therapeutic options
      for breast cancer.
AB  - The XXVII Annual Chemotherapy Foundation Symposium sponsored by The Mount Sinai
      School of Medicine is one of the leading forums for communication of important
      discoveries and new developments in cancer therapeutics. Here, we summarize and
      review the emerging advances in the treatment of breast cancer, which includes
      therapeutics in HER signaling, poly(ADP-ribose) polymerase inhibition, PI3K
      inhibitors and novel epithilones.

PMID- 20131992
TI  - Optimal management of uterine leiomyosarcoma.
AB  - Uterine leiomyosarcomas (LMSs) are rare tumors, comprising 1.3% of all uterine
      cancers. Primary therapy for localized disease entails complete surgical
      resection. The majority of patients recur within 2 years of primary therapy as
      these tumors tend to undergo early hematogenous spread. A randomized, controlled
      trial showed no improvement in the overall or disease-free survival with adjuvant
      radiotherapy, compared with observation, following resection of early-stage
      uterine LMS. A Phase II study of adjuvant chemotherapy following complete
      surgical resection of uterine LMS reported promising results. However, in the
      absence of Phase III randomized data demonstrating improved outcomes, the role of
      post-resection chemotherapy for early-stage disease remains experimental. For
      metastatic or unresectable LMS, systemic chemotherapy forms the mainstay of
      treatment. First-line treatment options include gemcitabine-docetaxel or
      doxorubicin with or without ifosfamide. Novel targeted therapies are under
      investigation in an attempt to devise more effective treatment strategies.

PMID- 20131993
TI  - Circulating tumor cells as prognostic marker in metastatic breast cancer.
AB  - Testing for circulating tumor cells has emerged as a new and promising tool for
      stratifying and monitoring patients with metastatic disease. Appropriate risk and
      biologic stratification in breast cancer is important for the development of more
      effectively tailored targeted therapies. To optimize patient care, it is
      important for the clinicians to rely on validated and robust tools able to
      provide accurate predictive and prognostic information for each patient at any
      time during treatment. The recent demonstration that the presence of circulating
      tumor cells predicts the prognosis at any time during the treatment of patients
      with metastatic breast cancer raises the possibility that this approach will
      allow for a true 'biologic staging' of the disease. Important questions regarding
      the biological characteristics of cells and the reasons for the reduced capacity
      of systemic treatments to arrest or eradicate the cancer were raised. A further
      study suggests that comprehensive analysis of circulating tumor cells is likely
      to provide new insights into the biology of breast cancer and contribute to
      defining novel treatments and better prediction of clinical benefit. Efforts are
      being made to genotype and phenotype micrometastatic cells. Considerable progress
      has been already accomplished which should lead to further noninvasive, real-time
      monitoring of these rare events in the adjuvant and metastatic settings.

PMID- 20131994
TI  - Trastuzumab and lapatinib beyond trastuzumab progression for metastatic breast
      cancer: strategies and pitfalls.
AB  - The discovery of HER2 gene amplification and protein overexpression in
      approximately 15-20% of breast cancers and access to the tailored humanized
      antibody, trastuzumab (Herceptin), have heralded a new era in breast cancer
      therapy. Trastuzumab combined with chemotherapy has caused marked tumor responses
      and increased overall survival in patients with metastatic breast cancer, and has
      also increased survival in the adjuvant setting after radical surgery. However,
      due to many causes, trastuzumab resistance usually occurs during treatment. In
      this event, possible options include the replacement of trastuzumab with
      lapatinib, the continuation of trastuzumab after disease progression with changed
      chemotherapy and the suspension of the use of targeted agents. New-generation
      tyrosine kinase inhibitors, which have a broader target, are now considered the
      key to treatment for breast cancer.

PMID- 20131995
TI  - Benefit of adjuvant chemotherapy in elderly ER-negative breast cancer patients:
      benefits and pitfalls.
AB  - Approximately 50% of breast cancer (BC) cases occur in women aged 65 and older,
      and more than 30% occur in those aged over 70, yet very old (older than 70)
      patients are under-represented in clinical trials. In the Oxford meta-analysis,
      the hazard ratios for recurrence and BC mortality in women aged over 70 were 0.88
      and 0.87, respectively, suggesting a benefit from chemotherapy in this group of
      patients as well; however, the large confidence intervals surrounding reductions
      in this subgroup reflect the small number of older patients recruited in
      randomized trials in Early Breast Cancer Trialists' Collaborative Group meta
      analyses. If we consider the tumor biology of BC in older adults, we will see
      that they are more likely to develop a tumor with high estrogen receptor (ER)-
      and/or progesterone receptor-positive status and a lower proliferative index.
      However, the biology of these tumors appears to change according to chronological
      age into aggressive forms diagnosed in these patients as well. This subgroup
      analysis for the benefit of adjuvant chemotherapy in elderly patients (at least
      65 years) is reported in a few studies, even though a limited statistical
      significance has been revealed. Retrospective evidences suggest that even more
      aggressive treatments such as taxanes and dose-dense schedule appear feasible
      (but probably more toxic) in the elderly. Age is no longer considered the only
      criterion for choosing the right treatment for patients with BC; in fact,
      functional status and comorbidity have to be taken into consideration as well.
      Fit elderly patients with more aggressive forms (node-positive and ER-poor
      disease) seem to obtain the same benefits as younger patients, and thus have to
      be treated in the same manner.

PMID- 20131996
TI  - Triple-negative/basal-like breast cancer: clinical, pathologic and molecular
      features.
AB  - Review of the spectrum of breast cancer tumor subtypes, which include basal-like,
      triple-negative and BRCA1-positive tumors, suggest that they have overlapping
      clinical, pathologic and molecular features, which are different from endocrine
      responsive breast cancers. Although response to chemotherapy is high in the
      neoadjuvant setting, the overall prognosis of this subset of tumors remains poor.
      Gene-profiling studies of this heterogeneous subset have lead to a better
      understanding of the molecular pathology of these aggressive tumors and the
      identification of possible therapeutic targets. Ongoing clinical studies of newer
      targeted agents, along with optimal chemotherapy, portend an improved clinical
      outcome for patients with aggressive basal-like/triple-negative breast cancer in
      the future.

PMID- 20131997
TI  - Biology and management of inflammatory breast cancer.
AB  - Inflammatory breast cancer is an aggressive subtype of a locally advanced breast
      cancer that is thought to account for approximately 1-5% of all newly diagnosed
      breast cancers diagnosed in the USA. Historically, IBC was considered to be a
      uniformly fatal disease with less than 5% of patients surviving past 5 years.
      With the advent of a multidisciplinary approach to management, survival outcomes
      have improved with 5-year survival rates of over 40% being reported. Research
      efforts are now focused on trying to better understand the epidemiological and
      molecular characteristics of this disease to further improve survival. Two genes,
      Rhoc GTPase and WISP3, have been identified that have been found to be
      concordantly altered in the majority of inflammatory breast cancer tumors and may
      serve as potential targets for future therapeutic agents. The purpose of this
      review is to summarize the latest epidemiological and molecular characteristics
      of IBC, describe the difficulties encountered in trying to clinically diagnose
      this entity, highlight the importance of a multidisciplinary approach and present
      some of the latest data on the management of this disease.

PMID- 20131998
TI  - Towards global consensus in the treatment of gastrointestinal stromal tumor.
AB  - The contemporary clinical landscape of gastrointestinal stromal tumor (GIST) has
      evolved rapidly over the past several years. Widely used treatment guidelines-
      from the European Society of Medical Oncology (ESMO) and the National
      Comprehensive Cancer Network--have recently been updated and represent the most
      up-to-date, comprehensive tools guiding the optimal management of GIST. In these,
      and in other published guidelines, close alignment among recommendations now
      exists for many of the clinical issues relevant to GIST management--surgery, use
      of the tyrosine kinase inhibitors imatinib and sunitinib and the role of pre- and
      post-operative imatinib, among others. This trend towards a global consensus in
      the treatment of GIST is the result of a relatively large amount of new data
      across the spectrum of its management. However, for some clinical considerations,
      recommendations still partially deviate. This review examines clinical
      recommendations and opinions on the management of GIST in the context of the
      latest data in the field and with an eye towards a multidisciplinary approach
      including surgical oncology, medical oncology, pathology and diagnostic
      radiology. Points of consensus are highlighted. Expert opinion is presented on
      management areas where no scientific evidence or firm recommendations currently
      exist; lingering and unresolved questions or issues are included. Within this
      framework, we present an evaluation of current global guidelines on the following
      areas in GIST management: surgery in the metastatic setting; neoadjuvant therapy;
      adjuvant therapy; mutational analysis; maintenance tyrosine kinase inhibitor
      therapy; and radiological imaging in GIST. A summary of consensus across these
      guidelines based on clinical trial data is juxtaposed with expert opinion where
      gaps in data still remain.

PMID- 20131999
TI  - Management of adult soft-tissue sarcoma of the extremities and trunk.
AB  - Soft-tissue sarcomas are a heterogeneous group of tumors consisting of
      approximately 100 distinct diagnoses. Management requires a multimodality
      approach with the input of pathologists, surgeons, radiation oncologists, medical
      oncologists and radiologists. In localized disease, the primary modality of
      treatment is wide-resection surgery, and the use of radiation therapy has
      improved local control rates for high-grade tumors. Currently, most localized
      tumors can be managed with limb-sparing treatment, and local control rates of 80
      90% can be seen with appropriate management. Improvements in classification and
      diagnosis of these tumors have led to the current idea that the specific
      histology is an important consideration when developing a treatment plan and may
      affect prognosis, although existing staging systems have not yet incorporated
      this parameter. Treatment of metastatic disease continues to be difficult, but
      current research focuses on clarifying molecular mechanisms of disease and
      identifying new potential targets for medical therapy. This review focuses on the
      current status of management of these tumors including a review of epidemiology,
      initial evaluation, and treatment including surgical, radiation, and medical
      aspects.

PMID- 20132000
TI  - Role of chemotherapy in the management of soft tissue sarcomas.
AB  - Soft tissue sarcomas are a diverse group of rare tumors that comprise 1% of all
      cancers. Few randomized trials of chemotherapy have been performed but there is a
      clear role for agents such as doxorubicin and ifosfamide in the palliation of
      advanced disease. There is uncertainty as to whether sequential single-agent
      treatment is equivalent to combination chemotherapy. For the majority of
      histological subtypes adjuvant chemotherapy is not of proven value, although
      there may be situations where it is advantageous. However, there are other
      subtypes, such as the Ewing's sarcoma family tumors, for which chemotherapy is an
      essential part of primary management and has definitely improved survival. Apart
      from Ewing's sarcoma family tumor and rhabdomyosarcoma, there is increasing
      specialization of chemotherapy according to histological subtype, such as the use
      of taxanes for angiosarcoma, gemcitabine and docetaxel for leiomyosarcoma, and
      trabectedin for leiomyosarcoma and liposarcoma, especially the myxoid/round cell
      variant. Nevertheless, there are serious limitations to existing treatment and
      novel therapies need to be developed.

PMID- 20132001
TI  - Do stem-like cells play a role in drug resistance of sarcomas?
AB  - Stem cells are defined by their unique characteristics, which include their
      abilities to self-renew and differentiate. Normal somatic stem cells have been
      isolated from various tissues such as bone marrow, adipose tissue, mammary glands
      and the nervous system. They are considered naturally resistant to
      chemotherapeutic agents because they express high levels of membrane transporter
      molecules, detoxifying enzymes and DNA repair proteins. Several recent studies
      have identified the presence of side populations in various cancer tissues, the
      so-called 'cancer stem cells', which are defined as the counterparts of stem
      cells in tumor tissues. These cancer stem cells possess stem-like properties,
      such as self-renewal and differentiation abilities, as well as playing a role in
      tumor initiation. Most sarcomas, which are thought to originate from mesenchymal
      stem cells, are highly malignant and approximately 30-40% of them show local
      and/or distant relapse (metastasis), even in the case of relatively
      chemosensitive tumors such as osteosarcomas and Ewing sarcomas. Several studies
      have suggested the presence of stem-like cell populations in sarcomas, based on
      their tumorigenicity and drug resistance. This review explores the issues of drug
      resistance of cancer stem cells in sarcomas and the possibilities of targeting
      cancer stem cells for the future treatment of sarcomas.

PMID- 20132002
TI  - Prognostic markers in osteosarcoma.
AB  - Osteosarcoma is the most common bone tumor seen in the pediatric and adolescent
      age group. Survival rates in osteosarcoma have improved considerably from 20 to
      65% since the 1980s with the advent of multiagent chemotherapy. Further
      improvement in survival has not been achieved owing to lack of well-validated
      prognostic markers and better therapeutic agents. Markers involved with
      angiogenesis, cell adhesion, apoptosis and cell cycle have been shown recently to
      play an important role in osteosarcoma growth, differentiation and metastasis.
      Over the coming years, the new molecular markers may be able not only to
      prognosticate osteosarcoma patients at baseline but also to serve as therapeutic
      targets and thereby improve survival rates further. Noninvasive imaging methods
      in osteosarcoma such as PET-CT and dynamic contrast enhanced and diffusion
      weighted MRI hold a lot of promise as surrogate methods for prognostication and
      response assessment.

PMID- 20132004
TI  - Viral inhibition assay: a CD8 T cell neutralization assay for use in clinical
      trials of HIV-1 vaccine candidates.
AB  - We have characterized an assay measuring CD8 T cell-mediated inhibition of human
      immunodeficiency virus (HIV) type 1 replication, demonstrating specificity and
      reproducibility and employing a panel of primary HIV-1 isolates. The assay uses
      relatively simple autologous cell culture and enzyme-linked immunosorbent assay,
      avoids generation of T cell clones, and can be performed with <2 million
      peripheral blood mononuclear cells. Efficient CD8 T cell-mediated cross-clade
      inhibition of HIV-1 replication in vitro was demonstrated in antiretroviral
      therapy-naive HIV-1-infected subjects with controlled viral replication in vivo
      but not in viremic subjects. An HIV-1 vaccine candidate, consisting of DNA and
      recombinant adenovirus 5 vectors tested in a phase I clinical trial, induced CD8
      T cells that efficiently inhibited HIV-1 in a HLA-I-dependent manner. Assessment
      of direct antiviral T cell function by this assay provides additional information
      to guide vaccine design and the prioritizing of candidates for further clinical
      trials.

PMID- 20132005
TI  - Redefinition of Tuberculosis-Associated Immune Reconstitution Syndromes in HIV
      Infected Individuals: A Need for New Clinical Tools.

PMID- 20132006
TI  - Is smoking a risk factor for influenza hospitalization and death?

PMID- 20132008
TI  - A new title and a new focus: Cellular Reprogramming.

PMID- 20132009
TI  - Master stem cell transcription factors and signaling regulation.
AB  - The present article reviews master stem cell transcription factors, their
      expression regulation network, and related signaling pathways with the aim of
      understanding the molecular mechanisms of pluripotent cell fate decisions. Oct4,
      Sox2, and Nanog are master transcription factors for maintenance of the
      undifferentiated state and self-renewal of embryonic stem cells (ESCs). In the
      mouse, they form a regulatory circuitry with coregulators, such as beta-catenin,
      Stat3, Myc, Klfs, Sall4, and Esrrb to control the expression of pluripotency
      related genes including themselves. The threshold expression of Oct4, Sox2, and
      Nanog for sustaining ESC properties depends on the synergistic effects among
      Stat3, beta-catenin, and Smad signaling pathway under the specific conditions of
      the ESC cytoplasmic microenvironment. Some of the salient differences in human
      ESC signaling pathways affecting their fate commitment are highlighted.

PMID- 20132010
TI  - Abnormal levels of transcript abundance of developmentally important genes in
      various stages of preimplantation bovine somatic cell nuclear transfer embryos.
AB  - Based on microarray data comparing gene expression of fibroblast donor cells and
      bovine somatic cell nuclear transfer (SCNT) and in vivo produced (AI)
      blastocysts, a group of genes including several transcription factors was
      selected for evaluation of transcript abundance. Using SYBR green-based real-time
      polymerase chain reaction (Q-PCR) the levels of POU domain class 5 transcription
      factor (Oct4), snail homolog 2 (Snai2), annexin A1 (Anxa1), thrombospondin
      (Thbs), tumor-associated calcium signal transducer 1 (Tacstd1), and transcription
      factor AP2 gamma (Tfap2c) were evaluated in bovine fibroblasts, oocytes, embryos
      30 min postfusion (SCNT), 12 h postfertilization/activation, as well as two-cell,
      four-cell, eight-cell, morula, and blastocyst-stage in vitro fertilized (IVF) and
      SCNT embryos. For every gene except Oct4, levels of transcript were
      indistinguishable between IVF and SCNT embryos at the blastocyst stage; however,
      in many cases levels of these genes during stages prior to blastocyst differed
      significantly. Altered levels of gene transcripts early in development likely
      have developmental consequences downstream. These results indicate that
      experiments evaluating gene expression differences between control and SCNT
      blastocysts may underestimate the degree of difference between clones and
      controls, and further offer insights into the dynamics of transcript regulation
      following SCNT.

PMID- 20132011
TI  - DNA methylation patterns reflect epigenetic reprogramming in bovine embryos.
AB  - To understand the epigenetic alterations associated with assisted reproduction
      technology (ART) and the reprogramming of gene expression that follows somatic
      cell nuclear transfer (SCNT), we screened a panel of 41 amplicons representing 25
      developmentally important genes on 15 different chromosomes (a total of 1079 CpG
      sites). Methylation analysis was performed on DNA from pools of 80 blastocysts
      representing three classes of embryos. This revealed a subset of amplicons that
      distinguish between embryos developing in vivo, produced in vitro, or
      reconstructed by SCNT. Following SCNT, we observed massive epigenetic
      reprogramming evidenced by reduced levels of methylation in the resultant
      embryos. Analysis of data from the 28 most informative amplicons (hotspot loci),
      representing more than 523 individual CpG sites, we discovered subsets of
      amplicons with methylation patterns that were unique to each class of embryo and
      may indicate metastable epialleles. Analysis of eight genes with respect to mRNA
      expression did not reveal a direct correlation with DNA methylation levels. In
      conclusion, this approach revealed a subset of amplicons that can be used to
      evaluate blastocyst quality and reprogramming following SCNT, and can also be
      employed for the localization of the epigenetic control regions within individual
      genes and for more general studies of stem cell differentiation.

PMID- 20132012
TI  - Rapid elimination of the histone variant MacroH2A from somatic cell
      heterochromatin after nuclear transfer.
AB  - Oocytes contain a maternal store of the histone variant MacroH2A, which is
      eliminated from zygotes shortly after fertilization. Preimplantation embryos then
      execute three cell divisions without MacroH2A before the onset of embryonic
      MacroH2A expression at the 16-cell stage. During subsequent development, MacroH2A
      is expressed in most cells, where it is assembled into facultative
      heterochromatin. Because differentiated cells contain heterochromatin rich in
      MacroH2A, we investigated the fate of MacroH2A during somatic cell nuclear
      transfer (SCNT). The results show that MacroH2A is rapidly eliminated from the
      chromosomes of transplanted somatic cell nuclei by a process in which MacroH2A is
      first stripped from chromosomes, and then degraded. Furthermore, MacroH2A is
      eliminated from transplanted nuclei by a mechanism requiring intact microtubules
      and nuclear envelope break down. Preimplantation SCNT embryos express endogenous
      MacroH2A once they reach the morula stage, similar to the timing observed in
      embryos produced by natural fertilization. We also show that the ability to
      reprogram somatic cell heterochromatin by SCNT is tied to the developmental stage
      of recipient cell cytoplasm because enucleated zygotes fail to support depletion
      of MacroH2A from transplanted somatic nuclei. Together, the results indicate that
      nuclear reprogramming by SCNT utilizes the same chromatin remodeling mechanisms
      that act upon the genome immediately after fertilization.

PMID- 20132013
TI  - Preferential loss of porcine chromosomes in reprogrammed interspecies cell
      hybrids.
AB  - Fusion of terminally differentiated somatic cells with pluripotent embryonic stem
      cells has been proposed as model for reprogramming the somatic cell genome, and
      may contribute to our understanding of the underlying mechanisms of this
      epigenetic process. We established an interspecies cell fusion model using murine
      embryonic stem cells (ESCs) and porcine fibroblasts. These inter-species fusion
      experiments yielded much lower conversion efficiency rates than murine
      intraspecies fusion. Nevertheless, two double-resistant mouse-pig hybrid clones
      could be generated. Reactivation of the porcine OCT4 gene, an essential
      pluripotent stem cell marker, and demethylation of the porcine OCT4 promoter in
      hybrid clone 1, suggested successful reprogramming of porcine chromosomes. A
      rapid loss of porcine chromosomes was observed during the selection phase.
      Spectral karyotyping (SKY) analysis showed that fusion-hybrid clone 1 carried a
      tetraploid mouse chromosome complement with only few pig chromosomes and/or
      chromosomal fragments. Hybrid clone 2 had a diploid set of murine chromosomes
      complements and also contained an interspecies chromosome fusion product.
      Interspecies cell fusion results in hybrid cells that retained the complement of
      mouse chromosomes and preferentially lose porcine chromosomes during colony
      expansion. Neither species-specific chromosomal segregation nor reprogrammed
      diploid porcine cells were observed. These findings indicate that generation of
      reprogrammed pluripotent diploid cells by cell fusion may require additional
      supporting provisions.

PMID- 20132014
TI  - Valproic acid enhances in vitro development and Oct-3/4 expression of miniature
      pig somatic cell nuclear transfer embryos.
AB  - The present study was carried out to examine the effects of valproic acid (VPA),
      a histone deacetylase inhibitor, on in vitro development of miniature pig somatic
      cell nuclear transfer (SCNT) embryos and on expression of a mouse Oct-3/4
      promoter-driven enhanced green fluorescent protein (EGFP) gene (EGFP expression
      only detected in Oct-3/4-expressing cells) introduced into donor cells for SCNT
      during their development. The addition of 4 mM VPA to embryo culture medium for
      48 h after activation significantly (p < 0.01) increased the blastocyst formation
      rate of SCNT embryos compared with the control, whereas VPA did not affect their
      cleavage rate. The rate of SCNT embryos expressing EGFP at 5 days of culture was
      not affected by the presence or absence of VPA treatment. At 7 days of culture,
      however, the addition of 4 mM VPA to embryo culture medium for 48 h after
      activation significantly (p < 0.05) increased the rate of SCNT embryos expressing
      EGFP compared with the control. The results indicate that VPA enhances the
      ability of miniature pig SCNT embryos to develop into blastocysts and maintains
      the ability of them to express Oct-3/4 gene.

PMID- 20132015
TI  - Histone deacetylase inhibitors improve in vitro and in vivo developmental
      competence of somatic cell nuclear transfer porcine embryos.
AB  - Faulty epigenetic reprogramming of somatic nuclei is likely to be a major cause
      of low success observed in all mammals produced through somatic cell nuclear
      transfer (SCNT). It has been demonstrated that the developmental competence of
      SCNT embryos in several species were significantly enhanced via treatment of
      histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA) to increase
      histone acetylation. Here we report that 50 nM TSA for 10 h after activation
      increased the developmental competence of porcine SCNT embryos constructed from
      Landrace fetal fibroblast cells (FFCs) in vitro and in vivo, but not at higher
      concentrations. Therefore, we optimized the application of another novel HDACi,
      Scriptaid, for development of porcine SCNT embryos. We found that treatment with
      500 nM Scriptaid significantly enhanced the development SCNT embryos to the
      blastocyst stage when outbred Landrace FFCs and ear fibroblast cells (EFCs) were
      used as donors compared to the untreated group. Scriptaid increased the overall
      cloning efficiency from 0.4% (untreated group) to 1.6% for Landrace FFCs and 0 to
      3.7% for Landrace EFCs. Moreover, treatment of SCNT embryos with Scriptaid
      improved the histone acetylation on Histone H4 at lysine 8 (AcH4K8) in a pattern
      similar to that of the in vitro fertilized (IVF) embryos.

PMID- 20132016
TI  - Pre- and postimplantation development of swine-cloned embryos derived from
      fibroblasts and bone marrow cells after inhibition of histone deacetylases.
AB  - The present study assessed changes in epigenetic markers and pre- and
      postimplantation development in somatic cell nuclear transfer (SCNT) porcine
      embryos after treatment with the inhibitor of histone deacetylases (HDACi),
      Trichostatin A (TSA). Embryos were generated using in vitro matured oocytes and
      nuclei from either a male fetal fibroblast (FF) cell line or bone marrow cells
      (BMC) from three adult sows. After nuclear transfer, oocytes were either exposed
      or not to 10 ng/mL TSA for 10 h starting 1 h after cell fusion. Samples of one
      cell stage and cleaved (two- to four-cell stage) embryos were fixed at 15 to 18 h
      or 46 to 48 h after cell fusion and immunocytochemically processed to detect
      histone H3 acetylation at lysine 14 (H3K14ac) or histone H3 dimethylation at
      lysine 9 (H3K9m2) using specific primary antibodies. TSA treatment increased the
      immunofluorescent signal for H3K14ac in cleaved embryos derived from both FF and
      BMC but did not affect H3K9m2. Development to the blastocyst stage was increased
      by TSA treatment (45.2 vs. 23.9%) in embryos produced from FF cells but not in
      those produced from BMC (30.6 vs. 27.4%). Cloned piglets were produced from both
      treatments when day 5 to 6 blastocyst-stage embryos derived from FF cells were
      transferred into the uterus of recipient females. Cloned piglets were also
      produced after the transfer of TSA-treated blastocysts derived from BMC of adult
      sows but not from control embryos. These findings suggest that the inhibition of
      histone deacetylases have similar effects on enhancing H3K14ac in SCNT embryos
      reconstructed from different cell types but the effect on in vitro and in vivo
      development seems to differ according to the nuclear donor cell type.

PMID- 20132017
TI  - Increasing histone acetylation of cloned embryos, but not donor cells, by sodium
      butyrate improves their in vitro development in pigs.
AB  - Previous studies have demonstrated that increased histone acetylation in donor
      cells or cloned embryos, by applying a histone deacetylase inhibitor (HDACi) such
      as trichostatin A (TSA), significantly enhances their developmental competence.
      However, its effect may vary with the type of HDACi and the target species, with
      some research showing nonsignificant or detrimental effects of TSA on in vitro
      and in vivo development of embryos. In this study, we show that sodium salt of
      butyric acid, a short-chain fatty acid produced naturally in the body by
      bacterial degradation of dietary fibers in the colon and rectum, increases
      histone acetylation in pig fibroblast and embryos at a concentration of 1.0 and
      5.0 mM, respectively. However, treatment of donor cells with NaBu did not affect
      the rate of blastocyst formation or embryo quality in terms of histone
      acetylation and total nuclei per blastocyst (p > 0.05). On the contrary,
      treatment of cloned pig embryos with NaBu for 4 h significantly enhanced (p <
      0.01) the rate of blastocyst formation (18.3 +/- 2.1 vs. 11.2 +/- 3.0%), although
      the total nuclei number per blastocyst did not differ. More importantly,
      blastocysts generated from NaBu-treated cloned embryos had increased levels of
      histone acetylation that was comparable to those of in vitro fertilized (IVF)
      embryos (36.7 +/- 3.6 vs. 45.9 +/- 2.5). In conclusion, our data suggest that
      histone hyperacetylation by NaBu treatment of cloned embryos, but not donor cell,
      enhances their in vitro development up to blastocyst stage.

PMID- 20132018
TI  - Generation of mouse embryonic stem cell lines from zona-free nuclear transfer
      embryos.
AB  - Pluripotent stem cells would have great potential in cell therapies and drug
      development when genetically matched with the patient; thus, histocompatible
      cells could be used in transplantation therapy or as a source of patient-specific
      cells for drug testing. Pluripotent embryonic stem cells (ESCs)-generated via
      somatic cell nuclear transfer (SCNT) or parthenogenesis (pESC)-are potential
      sources of histocompatible cells and tissues for transplantation. Earlier studies
      used the piezoelectric microinjection (PEM) technique for nuclear transfer (NT)
      in mouse. No specific studies examined zona-free (ZF) NT as an alternative NT
      method to generate genetically matched ESCs of a nuclear donor. In this study, we
      compared the efficiency of nuclear transfer-derived ESC (ntESC) line
      establishment from ZF-NT, ZF-parthenogenetic (PGA), and ZF-fertilized embryos
      with that of the PEM-NT method. Different nuclei donor cells [cumulus, ESC, and
      mouse embryonic fibroblast (MEF)] were used and the efficiency of ntESC
      derivation was investigated, along with their in vitro characterization. The ZF
      NT method's efficiency was higher than that of the PEM-NT using cumulus cells.
      When ESCs and cumulus cells were used as nuclear donor cells, they resulted in
      significantly higher ZF-NT-derived ntESC line establishment rates compared to MEF
      cells. In conclusion, the nuclear donor cell type significantly affected the
      efficiency of ntESC line establishment, and the ZF-NT method was efficient to
      establish pluripotent ntESC lines.

PMID- 20132020
TI  - Distribution of genes encoding four pathogenicity islands (VPaIs), T6SS, biofilm,
      and type I pilus in food and clinical strains of Vibrio parahaemolyticus in
      China.
AB  - Vibrio parahaemolyticus is a major cause of foodborne gastroenteritis in China,
      Japan, and other countries. The pandemic O3:K6 clone, which harbors thermostable
      direct hemolysin [tdh] gene and toxRS/new gene, is mainly responsible for the
      foodborne outbreaks after 1995. Previous studies showed that genes in the
      pathogenicity island-1 (VPaI-1) and VPaI-5 are harbored only by pandemic strains,
      whereas genes in VPaI-7 and type III secretion system 2 are closely associated
      with tdh-positive strains of V. parahaemolyticus. In this study, we examined the
      distribution of genes encoding VPaI-2, VPaI-3, VPaI-4, VPaI-6, type VI secretion
      systems (T6SS), biofilm, and type I pilus in 71 food and 116 clinical strains of
      V. parahaemolyticus. The results showed that most of the pandemic strains of V.
      parahaemolyticus harbored the complete genes of VPaI-2, T6SS, and type I pilus.
      In contrast, most of the pathogenic strains (harboring tdh gene or TDH-related
      hemolysin [trh] gene) and nonpathogenic strains (harboring neither tdh gene nor
      trh gene) contained partial genes of VPaI-2, T6SS, and type I pilus. Genes of
      VPaI-4 were exclusively present in the pandemic strains. Genes of VPaI-3 were
      present in most of the pandemic strains and a small percentage of nonpathogenic
      strains, mainly O3:K6 strains. VPaI-6 and biofilm-associated genes were harbored
      by almost all the strains, irrespective of their pandemic, pathogenic, or
      nonpathogenic traits.

PMID- 20132021
TI  - Existence of compensatory defense mechanisms against oxidative stress and
      hypertension in preeclampsia.
AB  - OBJECTIVE: Preeclampsia is a complex obstetrical syndrome characterized by
      hypertension and proteinuria. This syndrome is associated with oxidative stress,
      antioxidant imbalance and impaired production of vasoactive eicosanoids such as
      thromboxane A(2) (TXA(2)), a potent vasoconstrictor, and prostacyclin (PGI(2)), a
      well-known vasodilator. We hypothesized that there was a relationship between
      antioxidant vitamins, such as vitamin E and coenzyme Q(10) (CoQ(10)), and the
      production of vasoactive eicosanoids- PGI(2) and TXA(2)-potentially regulated by
      pro-oxidants and antioxidants in preeclampsia. METHODS: Therefore, the plasma
      levels of vitamin E, CoQ(10), TXA(2) and PGI(2) in normotensive (n = 30) and
      preeclamptic (n = 29) pregnancies were evaluated. Reduced and oxidized forms of
      vitamin E and CoQ(10) in blood were measured using a HPLC coupled to
      electrochemical detection. The levels of TXB(2) and 6-keto-PGF(1alpha), stable
      metabolites of TXA(2) and PGI(2) respectively, were measured by ELISA. RESULTS:
      The CoQ(10) oxidized/reduced ratio was significantly higher in preeclamptic
      compared to normotensive pregnancies (p = 0.04). A strong correlation between
      plasma levels of reduced vitamin E and CoQ(10), corrected for apolipoprotein B,
      was observed only in preeclampsia (r = 0.69, p < 0.0001). The 6-keto
      PGF(1alpha)/TXB(2) ratio was higher in preeclampsia than in controls (p = 0.02),
      and this ratio was correlated to the oxidized/reduced ratio of both, vitamin E
      and CoQ(10) in all pregnancies (p <0.023). CONCLUSION: The data indicated that
      CoQ(10) is a sensitive marker of oxidative stress in preeclampsia. The
      correlation between vitamin E and CoQ(10) suggested a coordinated defense
      mechanism against oxidation. Furthermore, the higher 6-keto-PGF(1alpha)/TXB(2)
      ratio that strongly correlated with oxidative stress markers, suggests a
      mechanism developed by the maternal cardiovascular system to counteract
      hypertension during preeclampsia.

PMID- 20132022
TI  - Erythrocyte markers of oxidative stress in higher age-group preeclamptic and
      normal pregnant mothers.
AB  - Preeclampsia can have significant impact on health of both mother and fetus. It
      had been proposed that maternal endothelial cell dysfunction is the key event
      resulting in the diverse clinical manifestations of preeclampsia and evidence has
      since accumulated. Research in recent times is indicative of the role of
      oxidative stress in the endothelial cell dysfunction. Preeclampsia is more common
      in first pregnancy and studies have further shown an increase in risk of
      preeclampsia with maternal age. The aim of this study was to explore the status
      of oxidative stress in higher age-group preeclamptic and normal pregnant mother.
      The study included 20 normal pregnant women and 60 preeclamptic women. They were
      allocated into 4 subgroups between ages 20-25, 26-30, 31-35, and 36-40.
      Erythrocytes were analyzed for the following antioxidant enzymes, i.e.,
      glutathione peroxidase, superoxide dismutase and catalase.Lipid peroxidation
      product, malondialdehyde, was analyzed to determine oxidative stress. The results
      showed an increase in oxidative stress, and high magnitude suppression/decrease
      in antioxidant enzymes activities in erythrocytes with increase in age groups in
      both preeclamptic and normal pregnant women. This indicates that an increase in
      the risk of preeclampsia with maternal age could be due to an increase in
      oxidative stress with age. This further attests to the role of oxidative stress
      in preeclampsia.

PMID- 20132023
TI  - Zuspan's scheme versus an alternative magnesium sulfate scheme: Randomized
      clinical trial of magnesium serum concentrations.
AB  - OBJECTIVE: The purpose of this study was to determine whether magnesium serum
      concentrations in patients with severe preeclampsia or eclampsia treated with two
      different magnesium sulfate schemes were different. METHODS: Fourteen patients
      were randomly assigned in the alternative scheme group and 15 in the Zuspan's
      group. The difference between the groups was that the intravenously administered
      maintenance dose was done with 1 g/h by continuous intravenous infusion in the
      Zuspan's group and 2g in bolus every two hours in the alternative scheme. Blood
      samples were collected previously to treatment and every 15 minutes during four
      hours after the beginning of treatment. The primary outcome measure was area
      under the curve and the t-test was used for statistical analysis with level of
      statistical significance of 5%. The evaluation of the punctual means at all
      moments in the alternative group was done with the repeated measures analysis of
      variance. RESULTS: There was no significant difference in the baseline
      characteristics between groups. In both schemes, magnesium serum concentration
      reaches a peak within 15 minutes and a new peak was observed after maintenance
      dose in the alternative scheme. The area under the curve was significantly lower
      in the alternative scheme than in the Zuspan's scheme (702.1 +/- 73.5 mg/dL vs
      796.1 +/- 94.6 mg/dL). CONCLUSION: The serum magnesium concentration of this
      randomized clinical trial doesn't support the use of the alternative scheme of
      magnesium sulfate to prevent or treat eclampsia.

PMID- 20132024
TI  - Lipid levels including oxidized LDL in women with history of preeclampsia.
AB  - Preeclampsia (PE), a leading cause of maternal and perinatal morbidity and
      mortality worldwide, is a hypertensive disorder of unknown aetiology
      characterized by proteinuria, coagulation abnormalities and different systemic
      manifestations. Since there are no studies regarding the evaluation of oxidized
      LDL (oxLDL) in women with a history of PE, we focused on the evaluation of lipid
      profile and oxLDL plasma concentration several years after pregnancy to see if
      these women have any modifications in these parameters that may be linked to the
      risk of cardiovascular disease (CVD) in the future. Ninety women with a history
      of PE and 60 controls in a median interval of 6 years after pregnancy were
      recruited. Plasma oxLDL levels were measured using a two-site enzyme immunoassay.
      Concentration of cholesterol, triglycerides (TG), HDL-cholesterol (HDLc) and LDL
      cholesterol (LDLc) were measured by automated enzymatic assays. To evaluate apoA
      and apoB levels automated immunoturbidimetric assays were used. In the group of
      women with a history of PE, gestational age at delivery was significantly earlier
      in comparison with the control group, whereas birth weight was significantly
      lower and there were more caesarean sections. Systolic and diastolic blood
      pressures were significantly higher in women with a history of PE than in the
      control group. Significantly higher obesity anthropometric markers (BMI and waist
      to-hip ratio) were found in women with a history of PE. As consistent with other
      authors' findings, blood pressure was higher in these women, but lipid profile
      did not seem to play a role in the increased risk of cardiovascular disease.

PMID- 20132025
TI  - Maternal serum ischemia-modified albumin: a biomarker to distinguish between
      normal pregnancy and preeclampsia?
AB  - OBJECTIVE: To determine whether a biological marker of ischemia, ischemia
      modified albumin (IMA), alone or normalized to albumin serum concentration, was
      modified during the course of pregnancy and so could be used for discrimination
      between normal pregnancy and preeclampsia. METHODS: Serum IMA concentrations and
      IMA to serum albumin ratio (IMA/alb) were compared in 22 nonpregnant healthy
      women (NP), 19 healthy pregnant women (HP) and 20 pre-eclamptic women (PE).
      Influence of age of gestation on these markers was also investigated. RESULTS:
      IMA to albumin ratio (IMA/alb) was significantly increased in HP compared with NP
      (IMA/alb. HP: 2.60 +/- 0.38 kU/g and IMA/alb. NP: 2.10 +/- 0.22 kU/g; p < 0.05).
      Both IMA and IMA/alb were significantly elevated during PE compared with HP (IMA
      HP: 98.4 +/- 9.2 kU/l and IMA PE 116.9 +/- 12.3 kU/l, p < 0.001; IMA/alb HP: 2.60
      +/- 0.38 kU/g and IMA/alb PE: 3.79 +/- 0.75 kU/g p < 0.001)). Both IMA and
      IMA/alb were increased in PE up to delivery. No correlation could be demonstrated
      between gestational age and maternal IMA both in HP (r = 0.13; p = 0.071) or PE
      (r = 0.05; p = 0.318). CONCLUSIONS: IMA and IMA normalized to albumin appear to
      be significantly increased during pathological pregnancies. These results confirm
      that IMA could be used as a biological marker of preeclampsia. These data need to
      be confirmed by determining intra-individual IMA change during normal and
      pathological pregnancy.

PMID- 20132026
TI  - Second trimester maternal serum cystatin C levels in preeclamptic and
      normotensive pregnancies: A small case-control study.
AB  - BACKGROUND/AIMS: Cystatin C (CC) is a marker of glomerular filtration rate (GFR)
      and is elevated in cases of established preeclampsia (PE). It also has widespread
      presence in extracellular space and high levels in PE might reflect placental
      ischemia. The aim of this study was to measure CC levels in the second trimester
      in women who subsequently develop PE and in those who remained normotensive.
      METHODS: Maternal serum taken at time of the anomaly scan from 15 women was
      analysed for CC and creatinine levels. Six women later developed PE and 9
      remained normotensive. RESULTS: Cystatin C levels were significantly higher in
      women who developed preeclampsia (mean value 0.76 vs. 0.53 mg/L, p = 0.008).
      However, creatinine levels showed no statistical difference (mean value 76.1 vs.
      65.5 micromol/L, p = 0.066). The range of CC was 0.41-0.55 mg/L in normotensive
      pregnancies and 0.50-1.26 mg/L in pregnancies with PE. CONCLUSION: This small
      observational study showed that serum CC is raised as early as the second
      trimester in women who subsequently develop PE in third trimester. Larger studies
      are needed to evaluate the potential role of CC as an early marker for the
      prediction of PE.

PMID- 20132027
TI  - Comment and reply on-comparison of walking versus stretching exercises to reduce
      the incidence of preeclampsia: A randomized clinical trial.

PMID- 20132028
TI  - Application of real-time polymerase chain reaction in detection of Entamoeba
      histolytica in pus aspirates of liver abscess patients.
AB  - Entamoeba histolytica is the second major cause of liver abscess disease in
      humans, particularly in developing countries. Recently, DNA molecular-based
      methods have been employed to enhance the detection of E. histolytica in either
      pus or stool specimens. In this study, the results of real-time polymerase chain
      reaction (PCR) to detect E. histolytica DNA in pus from liver abscess cases were
      compared with those of indirect hemagglutination assay on the corresponding serum
      samples. Bacterial cultures were also performed on the pus samples for the
      diagnosis of pyogenic liver abscess. The real-time PCR detected E. histolytica
      DNA in 23 of 30 (76.7%) pus samples, when compared with 14 of 30 (46.7%) serum
      samples in which anti-Entamoeba antibodies were detected by indirect
      hemagglutination assay and 4 of 30 (13.3%) pus samples that showed bacterial
      infection by culture. The use of real-time PCR is a promising detection method
      for diagnosis and epidemiology assessment of amoebic liver abscess.

PMID- 20132029
TI  - Influence of wet distiller's grains on prevalence of Escherichia coli O157:H7 and
      Salmonella in feedlot cattle and antimicrobial susceptibility of generic
      Escherichia coli isolates.
AB  - The current research examined the inclusion of 20% wet distiller's grains (WDG)
      fed with steam-flaked corn (SFC) or dry-rolled corn (DRC) in diets fed to feedlot
      cattle on fecal prevalence of Escherichia coli O157:H7 and Salmonella. Crossbred
      beef heifers (n = 272; average initial body weight (BW) = 354 kg) were blocked by
      BW and pen size and randomly assigned to treatment. Fecal samples from freshly
      voided fecal pats were collected from each pen on the day cattle shipped for
      slaughter (237 fecal samples: 72, 125, and 40 from cattle 132, 160, and 181 days
      on feed, respectively). Fecal samples were cultured quantitatively and
      qualitatively for the above pathogens. Populations of E. coli O157:H7 and
      Salmonella were generally low with very few samples containing quantifiable
      populations. Similarly, after enrichment, few samples were E. coli O157:H7
      positive in any collection with no treatment differences (p > 0.10). More samples
      were Salmonella positive during the first collection with an increased (p < 0.05)
      prevalence observed in the SFC and DRC treatments compared with DRC + WDG
      treatment. No other treatment differences were observed for Salmonella. Putative
      fecal coliform isolates (18 per treatment; first collection) were examined for
      antimicrobial susceptibility, and the majority were susceptible to all of the
      antibiotics examined. Most of the resistance was observed in the SFC (n = 3) and
      DRC (n = 4) treatments, and only one isolate in each of the two WDG treatments
      demonstrated resistance (one antibiotic each, streptomycin and tetracycline). All
      multidrug resistance (2-4 antibiotics) was observed in isolates cultured from the
      DRC and SFC treatments (n = 2 isolates in each treatment). Results of the current
      research found no significant effect of feeding WDG to feedlot cattle on fecal
      prevalence, at time of shipment for slaughter, of E. coli O157:H7, and only
      modest differences (decreases) in Salmonella prevalence with no apparent affect
      on antimicrobial susceptibility of fecal coliform isolates.

PMID- 20132030
TI  - Membrane and soluble ILT3 are critical to the generation of T suppressor cells
      and induction of immunological tolerance.
AB  - The tolerogenic phenotype of human dendritic cells is characterized by high cell
      surface expression of the inhibitory receptor ILT3. ILT3 signals both
      intracellularly inhibiting tyrosine phosphorylation, NF-kappaB and MAPK p38
      activity, transcription of certain co-stimulatory molecules, secretion of
      cytokines and chemokines, and extracellularly into the T cells with which the
      dendritic cells interact. Both ILT3(high) tolerogenic dendritic cells and soluble
      ILT3 induce CD4 Th anergy and differentiation of antigen specific CD8 T
      suppressor cells. Recombinant ILT3-Fc protein has important immunotherapeutic
      potential acting directly on activated T cells and promoting the induction of
      immunological tolerance.

PMID- 20132031
TI  - Effects of dam and/or seqA mutations on the fatty acid and phospholipid membrane
      composition of Salmonella enterica serovar Typhimurium.
AB  - We examined the phospholipids (Phls) and the membrane fatty acid (FA) composition
      in Salmonella enterica serovar Typhimurium dam and/or seqA mutants.
      Phosphatidylglycerol, phosphatidylethanolamine (PE), and cardiolipin (CL) are the
      major Phls present in all the strains and accounted for greater than 95% of the
      total lipid phosphorus. Phosphatidic acid and phosphatidylserine are the minor
      ones. The seqA mutant showed a decrease in PE and an increase in CL and
      phosphatidylglycerol proportion compared with the wild-type strain. The same
      changes were observed with the seqA dam double mutant. However, the dam mutation
      caused an unusual accumulation of CL with a significant decrease in the PE
      content, compared with the isogenic wild-type strain. FA composition of the total
      lipids and the different fractions containing Phls have been determined. The
      major saturated FAs (SFAs) and unsaturated FAs (UFAs) found were C(14:0), C(16:0)
      and C(16:1w7), C(18:1w9), respectively. Cyclic FAs, cyc(17:0) and cyc(19:0), were
      also present in appreciable amounts. Moreover, dam and/or seqA mutations caused a
      decrease in UFA/SFA ratio and there was a progressive reduction in the content of
      C(16:1w7) and C(18:1w9), going through the order seqA, dam/seqA, and dam mutants.
      This decrease in UFA content was compensated for in all strains by an increase in
      the corresponding C(17-) and C(19-) cyclic FAs. So these UFAs were converted to
      their cyclopropane derivatives, which resulted in a low UFA/SFA ratio. SeqA and
      Dam proteins might regulate FA biosynthesis and Phls composition of Salmonella
      enterica serovar Typhimurium.

PMID- 20132032
TI  - Multiplex real-time polymerase chain reaction assay for simultaneous detection
      and quantification of Salmonella species, Listeria monocytogenes, and Escherichia
      coli O157:H7 in ground pork samples.
AB  - Salmonella sp., Listeria monocytogenes, and Escherichia coli O157:H7 are
      foodborne pathogens capable of causing serious gastrointestinal illness. We
      previously described simultaneous detection of these pathogens by multiplex
      polymerase chain reaction (PCR) in 44 types of spiked food samples, including
      meat, produce, fish, and dairy products, targeting genes specific for each
      pathogen. Based on the previous work, a multiplex real-time PCR assay using
      fluorescent probes was developed to detect and accurately quantify Salmonella
      sp., L. monocytogenes, and E. coli O157:H7 in ground pork samples. The detection
      sensitivity for this method was 2.0 x 10(2) CFU/mL for each pathogen, and the
      quantification range was 10(2)-10(7) CFU/mL with a high correlation coefficient
      (R(2) > 0.99) and high PCR efficiency (84.2% to 99.2%). When this protocol was
      used for the detection of each of the pathogens in spiked pork samples, one cell
      per 25 g of inoculated sample after enrichment for 20 h could be detected within
      24 h. As a result, this multiplex real-time PCR assay will be valuable as a
      screening method for foods contaminated with these pathogens.

PMID- 20132033
TI  - Group B Streptococcus (GBS) urinary tract infection involves binding of GBS to
      bladder uroepithelium and potent but GBS-specific induction of interleukin
      1alpha.
AB  - Group B Streptococcus (GBS) causes urinary tract infections, but the pathogenic
      mechanisms underlying GBS urinary tract infections are unknown. We investigated
      whether uropathogenic GBS can bind to bladder uroepithelium to initiate urinary
      tract infection. Uropathogenic GBS isolated from a patient with acute cystitis
      bound to human T24 bladder uroepithelial cells in close association with F-actin
      in statistically significantly higher numbers compared with nonuropathogenic GBS.
      In vivo modeling using transurethrally infected mice revealed superior fitness of
      uropathogenic GBS for bladder colonization and potent uropathogenic GBS-specific
      up-regulation of interleukin 1alpha during infection. Thus, binding of
      uropathogenic GBS to uroepithelium and vigorous induction of interleukin 1alpha
      represents the initial stages of GBS urinary tract infection.

PMID- 20132034
TI  - Cesarean delivery and risk of intestinal bacterial infection.
AB  - BACKGROUND: An individual's intestinal bacterial flora is established soon after
      birth. Delivery by Cesarean section (c-section) deprives the newborn of
      colonization with maternal vaginal bacteria. We determined whether delivery by c
      section is associated with an altered risk of infection with intestinal bacterial
      pathogens. METHODS: In a cohort of 1.7 million Danes born 1973-2005 we identified
      cases of laboratory-confirmed non-typhoidal Salmonella species, Campylobacter
      species, Yersinia enterocolitica, Shigella species, and Shiga toxin-producing
      Escherichia coli from 1991-2005 in the National Registry of Enteric Pathogens.
      Using Poisson-regression we estimated confounder-adjusted incidence rate ratios
      (IRRs) for infection according to mode of delivery. RESULTS: During 14.0 million
      person-years of follow-up, 22,486 individuals were diagnosed with 1 intestinal
      bacterial infection. C-section was associated with a small increase in risk at
      age 1 to <2 years (IRR, 1.09; 95% confidence interval, 1.00-1.18) and at age 2 to
      <5 years (IRR, 1.08; 95% confidence interval, 1.00-1.17), but after age 5 years,
      there was no significant association. Assuming causality only 0.62% of intestinal
      bacterial infections were attributable to c-section. CONCLUSIONS: Mode of
      delivery appears not to be a clinically relevant determinant of risk for
      intestinal bacterial infections. The possible impact of increasing frequencies of
      c-section on the overall burden of intestinal bacterial infections appears
      negligible.

PMID- 20132035
TI  - Staphylococcal strains vary greatly in their ability to induce an inflammatory
      response in endothelial cells.
AB  - BACKGROUND: Staphylococcus aureus is an important human pathogen of endovascular
      diseases that can take an acute destructive course and/or develop into a chronic
      infection with a high rate of relapse. Despite good activity of the appropriate
      antimicrobial substances in vitro, these infections are often difficult to treat,
      perhaps because of the complex infection process of endovascular tissue. METHODS:
      We used the microarray technique to analyze the response of endothelial cells to
      different S. aureus strains, including highly virulent isolates (6850 and ST239);
      the Cowan I strain, which has a nonfunctioning accessory gene regulator (agr)
      quorum-sensing system; and various clinical isolates. RESULTS: All tested strains
      were equally invasive in endothelial cells and were found intracellularly, but
      they differed greatly in their ability to induce inflammation. Wild-type isolates
      (6850 and ST239) up-regulated a huge number of genes, including many genes
      involved in innate immunity. By contrast, Cowan I, which failed to express
      important virulence factors related to the agr system (eg, alpha-toxin and
      proteases), did not induce these dramatic changes in endothelial gene expression.
      Similar results were obtained with clinical isolates. CONCLUSION: Given that agr
      defective strains are commonly recovered during colonization and infection, agr
      deficiency might represent a strategy of S. aureus to hide intracellularly
      without provoking the host immune system and causing relapsing infections.

PMID- 20132036
TI  - Interleukin-6-174 G/C polymorphism is not associated with IL-6 expression and
      susceptibility to sporadic colon cancer.
AB  - Interleukin-6 (IL-6) has been implicated in tumorigenesis; however, its role is
      still far from being clearly defined. Regulation of IL-6 expression is highly
      complex, and additional complexity is introduced by single-nucleotide
      polymorphisms in the IL-6 gene. These single-nucleotide polymorphisms might
      influence mRNA transcription, which might in turn result in increased
      susceptibility to certain tumors. The aim of this study was to analyze IL-6 mRNA
      and protein expressions in sporadic colon cancer. Influence of IL-6-174 G/C
      polymorphism on IL-6 mRNA expression and sporadic colon cancer susceptibility was
      evaluated as well. The frequency of IL-6-174 G/C was analyzed by polymerase chain
      reaction-restriction fragment length polymorphism analysis. IL-6 mRNA and protein
      expressions were analyzed by real-time reverse transcription-polymerase chain
      reaction (RT-PCR) and immunohistochemistry. No statistically significant
      difference in IL-6 mRNA expression in tumor tissue compared with the
      corresponding normal tissue was observed (p = 0.116). No correlation was found
      between IL-6 mRNA and protein expressions and clinicopathological features of
      sporadic colon tumors. There was no association of IL-6-174 G/C genotypes with IL
      6 mRNA expression in colon tumors and corresponding normal mucous tissue (p =
      0.355; p = 0.152). Finally, there was no association of IL-6-174 G/C with
      susceptibility to sporadic colon cancer.

PMID- 20132037
TI  - Does gastrointestinal adverse drug reaction influence therapeutic effect in the
      treatment of rheumatoid arthritis?

PMID- 20132038
TI  - Bioaccumulation and bioavailability of copper and zinc on mineral-enriched
      mycelium of Grifola frondosa.
AB  - Grifola frondosa is an edible and medicinal mushroom. The bioaccumulation and
      potential biovailability of Cu and Zn were studied to obtain mycelium with
      potential properties as a food dietary supplement. Mycelia grown in the presence
      of nonmycotoxic concentrations of 100 and 200 ppm of Cu or 25 and 50 ppm of Zn
      accumulated 200-322 ppm and 267-510 ppm of Cu or Zn, respectively. When these
      enriched metal mycelia were subjected in vitro to a simulated gastrointestinal
      digestion, the solubility in these digestive fluids was 642-669 ppm and 102-530
      ppm, which represent 32-33% and 0.7-3.5% of the recommended daily intake (RDI)
      for Cu and Zn, respectively, in 1 g of mycelium. These results are discussed in
      relation to the RDI values exhibited by two commercial supplements, and arguments
      are given on the potential use of these mineral-enriched mycelia in capsules (in
      the case of Cu-enriched mycelia), in food preparations, and also as a component
      of cosmetic mixtures.

PMID- 20132039
TI  - Assessment of anti-inflammatory and antinociceptive activities of Olea europaea
      L.
AB  - Leaves and fruits of Olea europaea L. (Family Oleaceae) are used for the
      treatment of various kinds of diseases, i.e., rheumatism and hemorrhoids, and as
      a vasodilator in vascular disorders for ages in folk medicine. In order to
      evaluate this information, anti-inflammatory and antinociceptive activities of
      the ethanolic and n-hexane extracts prepared from the fruits of O. europaea were
      investigated. For the anti-inflammatory activity, the carrageenan-induced hind
      paw edema and acetic acid-induced increased capillary permeability models were
      used, whereas for the antinociceptive activity, the p-benzoquinone-induced
      writhing and hot plate tests in mice were used. The results revealed that the
      ethanolic extract did not show a significant anti-inflammatory or analgesic
      activity, whereas the n-hexane extract displayed 12.7-27.8% inhibition on the
      carrageenan-induced hind paw edema model at the 400 mg/kg dose, without inducing
      any apparent acute toxicity as well as gastric damage. Further studies are
      warranted to define and isolate the active anti-inflammatory and antinociceptive
      components from this plant, which may yield safe and effective agents to be used
      in the treatment of inflammatory disorders.

PMID- 20132040
TI  - Cytotoxic effects of bilberry extract on MCF7-GFP-tubulin breast cancer cells.
AB  - Bilberry (European blueberry) has been reported to have many biological effects,
      including anticancer activity. In this study, we investigated the
      antiproliferative effects of bilberry extract in relation to its ability to
      induce apoptosis and affect microtubule assembly and organization in MCF7 human
      breast cancer cells. We observed that bilberry extract inhibited cell
      proliferation in a concentration-dependent fashion with a 50% inhibitory
      concentration of 0.3-0.4 mg/mL, in concert with induction of apoptotic cell
      death. At these concentrations there was no selective inhibition of mitosis or
      any other cell cycle stage, nor was there any apparent effect on the microtubule
      or actin cytoskeletons. However, somewhat higher extract concentrations (0.5-0.9
      mg/mL) did cause an increase in the fraction of cells at the G(2)/M phase of the
      cell cycle, together with destruction of microtubules and formation of punctate
      tubulin aggregates in the cells. Bilberry extract at 0.3-0.4 mg/mL did not
      appreciably inhibit microtubule polymerization in vitro, but significant
      inhibition of polymerization (approximately 30%) did occur at higher extract
      concentrations (0.5-1 mg/mL). We conclude that bilberry extract as ingested by
      humans, not just the purified anthocyanins it contains, inhibits proliferation of
      and induces apoptosis in breast cancer cells at its lowest effective
      concentrations via a mechanism that does not involve action on microtubules or on
      mitosis. We further conclude that at somewhat higher concentrations the extract
      modifies microtubule organization in cells and causes accumulation of cells at
      mitosis by a direct action on microtubules.

PMID- 20132041
TI  - Antioxidant activity, inhibition of nitric oxide overproduction, and in vitro
      antiproliferative effect of maple sap and syrup from Acer saccharum.
AB  - Antioxidant activity, inhibition of nitric oxide (NO) overproduction, and
      antiproliferative effect of ethyl acetate extracts of maple sap and syrup from 30
      producers were evaluated in regard to the period of harvest in three different
      regions of Quebec, Canada. Oxygen radical absorbance capacity (ORAC) values of
      maple sap and syrup extracts are, respectively, 12 +/- 6 and 15 +/- 5 micromol of
      Trolox equivalents (TE)/mg. The antioxidant activity was also confirmed by a cell
      based assay. The period of harvest has no statistically significant incidence on
      the antioxidant activity of both extracts. The antioxidant activity of pure maple
      syrup was also determined using the ORAC assay. Results indicate that the ORAC
      value of pure maple syrup (8 +/- 2 micromol of TE/mL) is lower than the ORAC
      value of blueberry juice (24 +/- 1 micromol of TE/mL) but comparable to the ORAC
      values of strawberry (10.7 +/- 0.4 micromol of TE/mL) and orange (10.8 +/- 0.5
      micromol of TE/mL) juices. Maple sap and syrup extracts showed to significantly
      inhibit lipopolysaccharide-induced NO overproduction in RAW264.7 murine
      macrophages. Maple syrup extract was significantly more active than maple sap
      extract, suggesting that the transformation of maple sap into syrup increases NO
      inhibition activity. The highest NO inhibition induced by the maple syrup
      extracts was observed at the end of the season. Moreover, darker maple syrup was
      found to be more active than clear maple syrup, suggesting that some colored
      oxidized compounds could be responsible in part for the activity. Finally, maple
      syrup extracts (50% inhibitory concentration = 42 +/- 6 microg/mL) and pure maple
      syrup possess a selective in vitro antiproliferative activity against cancer
      cells.

PMID- 20132042
TI  - Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents.
AB  - Bean pods (Phaseolus vulgaris) are among the most widely used traditional
      remedies against diabetes mellitus. Historical knowledge is summarized and
      compared to recent study results. Reports dating from the first half of the
      20(th) century as well as recent publications show contradictory results. It
      seems that Phaseolus preparations should not be considered the first choice in
      phytopharmaceutical treatment of diabetes or lead structure research. To be
      effective, fairly high doses of aqueous extracts need to be given. Because of
      their fiber content and an alpha-amylase inhibitory effect, beans might be more
      useful as food components in preventing or ameliorating type 2 diabetes.

PMID- 20132043
TI  - Ethanolic extracts of Brassica campestris spp. rapa roots prevent high-fat diet
      induced obesity via beta(3)-adrenergic regulation of white adipocyte lipolytic
      activity.
AB  - The influence of ethanolic extracts of Brassica campestris spp. rapa roots (EBR)
      on obesity was examined in imprinting control region (ICR) mice fed a high-fat
      diet (HFD) and in 3T3-L1 adipocytes. The ICR mice used were divided into regular
      diet, HFD, EBR (50 mg/kg/day EBR administered orally), and orlistat (10 mg/kg/day
      orlistat administered orally) groups. The molecular mechanism of the anti-obesity
      effect of EBR was investigated in 3T3-L1 adipocytes as well as in HFD-fed ICR
      mice. In the obese mouse model, both weight gain and epididymal fat accumulation
      were highly suppressed by the daily oral administration of 50 mg/kg EBR for 8
      weeks, whereas the overall amount of food intake was not affected. EBR treatment
      induced the expression in white adipocytes of lipolysis-related genes, including
      beta(3)-adrenergic receptor (beta(3)-AR), hormone-sensitive lipase (HSL), adipose
      triglyceride lipase, and uncoupling protein 2. Furthermore, the activation of
      cyclic AMP-dependent protein kinase, HSL, and extracellular signal-regulated
      kinase was induced in EBR-treated 3T3-L1 cells. The lipolytic effect of EBR
      involved beta(3)-AR modulation, as inferred from the inhibition by the beta(3)-AR
      antagonist propranolol. These results suggest that EBR may have potential as a
      safe and effective anti-obesity agent via the inhibition of adipocyte lipid
      accumulation and the stimulation of beta(3)-AR-dependent lipolysis.

PMID- 20132044
TI  - Antitumor activities and immunomodulatory effects of ginseng neutral
      polysaccharides in combination with 5-fluorouracil.
AB  - A neutral polysaccharide fraction (WGPN) prepared from Panax ginseng C.A. Meyer
      by hot water extraction and DEAE-cellulose chromatography was tested for its
      anticancer activity alone and in combination with 5-fluorouracil (5-FU) in
      Sarcoma-180 (S180) tumor-bearing mice by intragastric administration. WGPN alone
      inhibited S180 tumor growth in a bell-shaped dose-response curve, and the
      combination with 5-FU showed a synergistic effect. Studies of various
      immunological activities in S180-bearing mice revealed that WGPN stimulated the
      proliferation of lymphocytes, increased natural killer cell cytotoxicity,
      enhanced the phagocytosis and nitric oxide production by macrophages, and
      increased the level of tumor necrosis factor-alpha in serum. In combination with
      5-FU, WGPN mitigated damage to the immune system caused by 5-FU in S180-bearing
      mice. These results suggest that WGPN might be a potential adjuvant for
      chemotherapeutic drugs.

PMID- 20132045
TI  - Combining fructooligosaccharide and dried plum has the greatest effect on
      restoring bone mineral density among select functional foods and bioactive
      compounds.
AB  - Functional foods and/or their bioactive compounds playing a role in improving
      skeletal health have received considerable attention. The objective of the
      present study was to determine the extent to which certain functional foods as
      (1) whole, e.g., dried plum (DP), figs, dates, raisin, and blueberry, (2)
      fractionated, e.g., DP puree, DP juice, and DP pulp/skin, or (3) isolated, e.g.,
      DP polyphenols, fructooligosaccharides (FOS), and beta-hydroxy-beta
      methylbutyrate, forms reverse bone loss in an ovariectomized (Ovx) rat model of
      osteoporosis. Additionally, some of these components were tested in reversal of
      bone loss in combination. For this purpose, 180 3-month-old female Sprague-Dawley
      rats were divided into 15 groups (n = 12) and either Ovx (14 groups) or sham
      operated (Sham, one group). Rats were maintained on a semipurified standard diet
      for 45 days after surgery to establish bone loss. Thereafter, rats were placed on
      one of the following dietary treatments for 60 days: casein-based diet (Sham and
      Ovx). The remaining 13 Ovx groups were placed on various treatment diets. Results
      showed that diets supplemented with 5% FOS + 7.5% DP was most effective in
      reversing both right femur and fourth lumbar bone mineral density and fourth
      lumbar calcium loss while significantly decreasing trabecular separation. There
      were no significant effects of treatment on serum or urine measures of bone
      turnover. Although other treatments were good at altering some bone parameters,
      none had the success in altering several bone health indicators as the diets
      supplemented with 5% FOS + 7.5% DP. The findings of this study suggest the
      combination of 5% FOS + 7.5% DP is capable of reversing Ovx-induced bone loss.

PMID- 20132046
TI  - Antiproliferative activity of Greek propolis.
AB  - The butanolic extract and the isolated chemical constituents, mainly diterpenes
      and flavonoids, from Greek propolis have been tested for their cytostatic
      activities against human malignant and normal cell strains. The extract and the
      diterpenes were found to be the most active against HT-29 human colon
      adenocarcinoma cells, without affecting normal human cells. Manool, a diterpene
      isolated for the first time from Greek propolis, was the most active compound,
      arresting the cancer cells at the G(2)/M phase of the cell cycle.

PMID- 20132047
TI  - Combination of genistin and fructooligosaccharides prevents bone loss in ovarian
      hormone deficiency.
AB  - We have reported that soy isoflavones are capable of preventing loss of bone
      mineral density (BMD) in rats due to ovariectomy. The intestinal microflora is
      important in rendering soy isoflavones bioavailability by facilitating their
      conversion to equol. Hence, substances that can modulate the intestinal
      microflora could affect the bioavailability of isoflavones. The purpose of this
      study was to examine whether combination of genistin and fructooligosaccharides
      (FOS), a prebiotic, can enhance the effects of soy isoflavones on bone in
      ovariectomized (OVX) female rats. Forty-eight 90-day-old female Sprague-Dawley
      rats were either sham-operated (Sham; one group) or Ovx (three groups) and were
      placed on dietary treatment for 50 days. The Sham and one Ovx group received a
      control diet, and the remaining Ovx groups received genistin-rich isoflavones
      diet (Ovx+G) or genistin-rich isoflavones and FOS diet (Ovx+G+FOS). After 50
      days, blood and bone specimens were collected for analysis. The genistin-rich
      isoflavones diet was able to significantly increase the whole-body, right femur,
      and fourth lumbar BMD by 1.6%, 1.48%, and 1.3%, respectively in comparison with
      the Ovx control. The combination of genistin-rich isoflavones diet and 5% FOS
      further increased whole-body, right femur, and fourth lumbar BMD more compared to
      the genistin-rich isoflavones diet. Our findings suggest that although a genistin
      rich isoflavones diet can increase the BMD in rats with Ovx-induced bone loss,
      combination of genistin-rich isoflavones and FOS had greater effect in preventing
      bone loss in this rat model.

PMID- 20132048
TI  - In remembrance: Michael J. Lysaght, 1942-2009.

PMID- 20132049
TI  - Lack of effect of moderate hypothermia on brain tissue oxygenation after acute
      intracranial hypertension in pigs.
AB  - In this study, we explored the effect of moderate hypothermia on brain tissue
      oxygenation following acute intracranial hypertension in micropigs. Twenty
      healthy juvenile micropigs weighting 4-6 kg were randomized into two groups: a
      normothermia group (n = 10) and a moderate hypothermia group (n = 10). The
      animals were intravenously anesthetized with propofol (4 mg/kg), an endotracheal
      tube was inserted, and mechanical ventilation was begun. Autologous arterial
      blood was injected into the left frontal lobe to establish acute intracerebral
      hematoma and intracranial hypertension (intracranial pressure [ICP] >40 mm Hg) in
      all animals. Cooling was initiated at 30 min after injection of the blood, and
      was achieved via the use of an ice bath and ice packs. In the hypothermia group,
      the brain temperature decreased to 33-34 degrees C. Brain temperature was
      maintained at 37 +/- 0.3 degrees C in the normothermia group. The ICP, cerebral
      perfusion pressure (CPP), brain tissue oxygen pressure (P(br)O(2)), brain tissue
      carbon dioxide pressure (P(br)CO(2)), and brain tissue pH value (pH(br)) were
      continuously monitored for 3 h in all animals. Compared to normothermia group,
      ICP values significantly decreased and CPP markedly improved in the hypothermia
      group (p < 0.05). Further, pH(br) also markedly increased and P(br)CO(2)
      decreased significantly in the hypothermia group (p < 0.05). However, P(br)O(2)
      did not statistically significantly improve in the hypothermia group (p > 0.05).
      In sum, moderate hypothermia significantly decreased ICP, reduced P(br)CO(2), and
      increased pH(br) values, but did not improve cerebral oxygenation following acute
      intracranial hypertension.

PMID- 20132050
TI  - Addition of a single E2 binding site to the human papillomavirus (HPV) type 16
      long control region enhances killing of HPV positive cells via HPV E2 protein
      regulated herpes simplex virus type 1 thymidine kinase-mediated suicide gene
      therapy.
AB  - Human papillomavirus type 16 (HPV16) is associated with the development of
      anogenital cancers and their precursor lesions, intraepithelial neoplasia.
      Treatment strategies against HPV-induced intraepithelial neoplasia are not HPV
      specific and mostly consist of physical removal or ablation of lesions. We had
      previously designed an HPV-specific approach to kill HPV-infected cells by the
      herpes simplex virus type 1 thymidine kinase (TK) gene driven by HPV E2 binding
      to E2-binding sites (E2BS) in the native HPV16 long control region. E2-induced TK
      expression renders the cells sensitive to the prodrug ganciclovir. To optimize
      this therapeutic approach, we modified the native long control region by adding
      variable numbers of E2BS adjacent to E2BS4, resulting in greatly increased cell
      death in HPV-positive cell lines with variable levels of E2 protein expression
      and no reduction in HPV specificity. Our results showed maximum increase in TK
      expression and cell killing when one additional E2BS was added adjacent to E2BS.
      As HPV-infected patients also exhibit variable E2 expression across lesions and
      within a lesion, this approach may potentiate the clinical utility of the herpes
      simplex virus type 1 TK/ganciclovir therapeutic approach.

PMID- 20132051
TI  - Toll-like receptor 2 mediates proliferation, survival, NF-kappaB translocation,
      and cytokine mRNA expression in LIF-maintained mouse embryonic stem cells.
AB  - Toll-like receptor (TLR) activation is important in immune responses and in
      differentiation of hematopoietic stem cells. We detected mRNA expression of TLRs
      1, 2, 3, 5, and 6, but not TLRs 4, 7, 8, and 9 in murine (m)ESC line E14, and
      noted high cell surface protein expression of TLR2, but not TLR4, for mESC lines
      R1, CGR8, and E14. ESC lines were cultured in the presence of leukemia inhibitory
      factor (LIF). Pam(3)Cys enhanced proliferation and survival of the 3 ESC lines.
      In contrast, lipopolysaccharide (LPS) decreased proliferation and survival.
      Pam(3)Cys and LPS effects on proliferation and survival were blocked by antibody
      to TLR2, suggesting that effects of both Pam(3)Cys and LPS on these mESC lines
      were likely mediated through TLR2. E14 ESC line expressed MyD88. Pam(3)Cys
      stimulation of E14 ESCs was associated with induced NF-kappaB translocation,
      enhanced phosphorylation of IKK-alpha/beta, and enhanced mRNA, but not protein,
      expression of tumor necrosis factor-alpha, interferon-gamma, and IL-6. TLR2
      activation by Pam(3)Cys or inhibition by LPS was not associated with changes in
      morphology or expression of alkaline phosphatase, Oct4, SSEA1, KLF4, or Sox2,
      markers of undifferentiated mESCs. Our studies identify TLR2 as present and
      functional in E14, R1, and CGR8 mESC lines.

PMID- 20132052
TI  - A multipotent neural crest-derived progenitor cell population is resident within
      the oral mucosa lamina propria.
AB  - Wounds within the oral mucosa, similarly to fetal wounds, exhibit rapid healing
      with reduced scarring. We hypothesized that a progenitor population resident
      within the oral mucosal lamina propria (OMLP) contributes to this preferential
      healing. Progenitor cells (PC) were reliably isolated from the OMLP by
      differential adhesion to fibronectin. Isolated colonies originating from a single
      cell demonstrated a rapid initial phase of proliferation, completing in excess of
      50 population doublings (PDs) before entering cellular senescence. These data
      were supported by the expression of active telomerase within both developing
      colonies and expanded clones as assessed by immunocytochemistry (ICC) and the
      quantitative telomeric repeat amplification protocol. FACS analysis confirmed
      expression of the stem cell markers CD44, CD90, CD105, and CD166, but negative
      expression of CD34 and CD45 ruling out a hematopoietic or fibrocyte origin for
      these progenitors. A neural crest origin was confirmed by increased colony
      forming efficiency (CFE) in the presence of Jagged 1 and the expression of a
      number of neural crest markers within the developing colonies by ICC and serially
      passaged clones by Western blotting. The multipotency of this novel PC population
      was demonstrated by differentiation of the cells down both mesenchymal
      (chondrogenic, osteoblastic, and adipogenic) and neuronal (neuron and Schwann
      like cells) cell lineages. This article reports for the first time, the isolation
      and characterization of a novel, clonally derived PC population resident within
      the OMLP. The attributes of this adult stem cell (ASC) population and its
      accessibility lends itself to future therapeutic applications.

PMID- 20132053
TI  - Acne in skin of color: practical approaches to treatment.
AB  - Acne vulgaris, one of the most commonly encountered conditions in dermatology,
      affects individuals in all racial and ethnic groups, yet clinical presentation
      varies among different skin types. Acne, particularly when it is severe, may
      significantly impact an individual's quality of life and psychological well
      being. Potential sequelae, such as postinflammatory hyperpigmentation and keloid
      scarring, occur more frequently in individuals with skin of color and may be long
      lasting or permanent. Acknowledging the potentially long-term physical and
      emotional scars caused by acne vulgaris, attention has focused on management
      strategies that limit the disease to an early stage. Early and efficacious
      treatment of acne in skin of color patients may minimize pigmentary abnormalities
      and keloid scarring. By recognizing racial and ethnic differences in clinical
      presentation and potential sequelae, treatment regimens may be tailored to ensure
      favorable outcomes for patients of all skin types.

PMID- 20132054
TI  - Modification of mesenchymal stem cells for cardiac regeneration.
AB  - IMPORTANCE OF THE FIELD: Mesenchymal stem cells (MSCs) have the greatest
      potential for use in cell-based therapy of human heart diseases, especially in
      myocardial infarcts. The therapeutic potential of MSCs in myocardial repair is
      based on the ability of MSCs to directly differentiate into cardiac tissue and on
      the paracrine actions of factors released from MSCs. However, the major obstacle
      in the clinical application of MSC-based therapy is the poor viability of the
      transplanted cells due to harsh microenvironments like ischemia, inflammation
      and/or anoikis in the infarcted myocardium. Recently, various approaches have
      been implemented in an effort to improve the survival of implanted MSCs through
      ex vivo manipulation of MSCs. AREAS COVERED IN THIS REVIEW: Major obstacles in
      MSC-based therapy are discussed, along with recent advances for enhancing
      therapeutic potential of engrafted MSCs from the past decade. WHAT THE READER
      WILL GAIN: This review focuses primarily on ex vivo manipulation of MSCs before
      transplantation, which includes pretreatment, preconditioning and genetic
      modification of MSCs, and future directions. TAKE HOME MESSAGE: Modification of
      MSCs before transplantation has developed into a promising option for enhancing
      the beneficial effects of MSC-based therapy for cardiac repair after myocardial
      infarction.

PMID- 20132055
TI  - Role of the SDF-1-CXCR4 axis in stem cell-based therapies for ischemic
      cardiomyopathy.
AB  - IMPORTANCE OF THE FIELD: Ischemic disorders are the leading cause of mortality
      worldwide, current therapies only delay progression of the disease. Data suggest
      a role of the SDF-1-CXCR4 axis in attenuation of ischemic disorders. AREAS
      COVERED IN THIS REVIEW: We discuss the importance of SDF-1-CXCR4 interactions
      during development and postnatal mobilization and migration of stem cells. We
      focus on the role of the SDF-1-CXCR4 axis in stem-cell-based applications for
      attenuation of ischemic cardiomyopathy. WHAT THE READER WILL GAIN: During
      development the SDF-1-CXCR4 axis plays a critical role in gradient-guided cell
      movements. In adults, the SDF-1-CXCR4 axis is involved in retention and
      mobilization of stem cells. Since SDF-1 is upregulated during hypoxic tissue
      damage, strategies to augment or stabilize SDF-1 have been utilized to target
      blood-derived stem cells to ischemic tissue. We exploited this concept by
      preventing SDF-1 degradation with dipeptidylpeptidaseIV (DPPIV) inhibition and
      mobilization of stem cells by G-CSF after acute myocardial infarction. This
      targeted CD34(+)CXCR4(+) cells to ischemic heart and attenuated ischemic
      cardiomyopathy. TAKE HOME MESSAGE: The SDF-1-CXCR4 axis plays a role in stem cell
      homing during embryogenesis and adulthood especially after ischemia. Preserving
      functional SDF-1 by DPPIV inhibition after ischemia may enhance stem cell
      therapies.

PMID- 20132057
TI  - Oncolytic (replication-competent) adenoviruses as anticancer agents.
AB  - IMPORTANCE OF THE FIELD: Whilst therapies for neoplasies have advanced
      tremendously in the last few decades, there is still a need for new anti-cancer
      treatments. One option is genetically-engineered oncolytic adenovirus (Ad)
      'vectors'. These kill cancer cells via the viral replication cycle, and amplify
      the anti-tumor effect by producing progeny virions able to infect neighboring
      tumor cells. AREAS COVERED IN THIS REVIEW: We provide a description of basic Ad
      biology and summarize the literature for oncolytic Ads from 1996 to the present.
      WHAT THE READER WILL GAIN: An overall view of oncolytic Ads, the merits and
      drawbacks of the various features of these vectors, and obstacles to further
      development and future directions for research. TAKE HOME MESSAGE: Ads are
      attractive for gene therapy because they are relatively innocuous, easy to
      produce in large quantities, genetically stable, and easy to manipulate. A
      variety of have been constructed and tested, in pre-clinical and clinical
      experiments. Oncolytic Ads proved to be remarkably safe; no dose-limiting
      toxicity was observed in any clinical trial, and the maximum tolerated dose was
      not reached. At present, the major challenge for researchers is to increase the
      efficacy of the vectors, and to incorporate oncolytic virotherapy into existing
      treatment protocols.

PMID- 20132058
TI  - The evolving role of dendritic cells in cancer therapy.
AB  - IMPORTANCE OF THE FIELD: Dendritic cells (DC) are a clear choice for use in
      cancer immunotherapy, and much research has focused on generating DC for clinical
      use. Although DC therapy has been successful in inducing specific anti-tumour
      immune responses, these have rarely translated into clinical efficacy. AREAS
      COVERED IN THIS REVIEW: We examine some of the components of generating DC for
      therapy, including their culture, antigen loading and delivery, and discuss why
      DC therapy has not yet delivered substantial clinical benefit. We also examine
      more novel approaches, such as the potential for combination DC-based
      immunomodulatory strategies. WHAT THE READER WILL GAIN: Given the highly
      immunosuppressive tumour environment, many of the approaches to DC vaccination
      are unlikely to result in effective therapy, as even successfully primed T cells
      may fail to infiltrate tumours or be anergized after entry. Broader approaches
      against multiple tumour-associated antigens in the context of overcoming tumour
      immune suppression are likely to prove more successful. The combination of
      oncolytic viral therapy with DC vaccines may promote an inflammatory tumour
      environment, inducing optimal DC activation, T cell priming and effective
      therapy. TAKE HOME MESSAGE: Evolving DC-based therapeutic strategies addressing
      multiple components of tumour-immune system interactions may yield substantial
      benefits for patients.

PMID- 20132056
TI  - Challenges of T cell therapies for virus-associated diseases after hematopoietic
      stem cell transplantation.
AB  - IMPORTANCE OF THE FIELD: Hematopoietic stem cell transplantation (HSCT) is the
      treatment of choice for many hematological malignancies and genetic disorders.
      The majority of patients do not have a human leukocyte antigen (HLA) identical
      sibling donor, and alternative stem cell sources include HLA-matched or
      mismatched unrelated donors and haploidentical related donors. However,
      alternative donor HSCT are associated with three major complications i) graft
      rejection; ii) graft-versus-host disease (GvHD); and iii) delayed immune
      reconstitution leading to viral infections and relapse. AREAS COVERED IN THIS
      REVIEW: Graft rejection and the risk of GvHD can be significantly reduced by
      using intensive conditioning regimens, including in vivo T cell depletion as well
      as ex vivo T cell depletion of the graft. However, the benefits of removing
      alloreactive T cells from the graft are offset by the concomitant removal of T
      cells with anti-viral or anti-tumor activity as well as the profound delay in
      endogenous T cell recovery post-transplant. Thus, opportunistic infections, many
      of which are not amenable to conventional small-molecule therapeutics, are
      frequent in these patients and are associated with significant morbidity and high
      mortality rates. This review discusses current cell therapies to prevent or treat
      viral infections/reactivations post-transplant. WHAT THE READER WILL GAIN: The
      reader will gain an understanding of the current state of cell therapy to prevent
      and treat viral infections post-HSCT, and will be introduced to preclinical
      studies designed to develop and validate new manufacturing procedures intended to
      improve therapeutic efficacy and reduce associated toxicities. TAKE HOME MESSAGE:
      Reconstitution of HSCT recipients with antigen-specific T cells, produced either
      by allodepletion or in vitro reactivation, can offer an effective strategy to
      provide both immediate and long-term protection without harmful alloreactivity.

PMID- 20132059
TI  - Viral vector-mediated gene transfer for CNS disease.
AB  - IMPORTANCE OF THE FIELD: Gene therapy is a promising strategy for the treatment
      of many neurological disorders that currently lack effective treatment. Recent
      improvements in vectorology and vector engineering have improved overall safety
      and delivery of viral vectors. AREAS COVERED IN THIS REVIEW: This review
      discusses the current state of viral vector development and clinical use, as well
      as routes of delivery, and clinical trials for neurological disorders. WHAT THE
      READER WILL GAIN: Viral vectors may be delivered directly or remotely to the CNS,
      largely depending on the nature of the disease and the tropism of the vector.
      Nonetheless, delivery remains one of the major limitations of successful gene
      transfer to the CNS. TAKE HOME MESSAGE: Although the majority of clinical trials
      have centered on gene replacement and neuroprotection approaches, the field is
      advancing in the direction of neuromodulation, gene silencing and other newer
      strategies.

PMID- 20132060
TI  - AAV-directed muscular dystrophy gene therapy.
AB  - IMPORTANCE OF THE FIELD: Muscle-directed gene therapy for genetic muscle diseases
      can be performed by the recombinant adeno-associated viral (rAAV) vector delivery
      system to achieve long-term therapeutic gene transfer in all affected muscles.
      AREAS COVERED IN THIS REVIEW: Recent progress in rAAV-vector-mediated muscle
      directed gene transfer and associated techniques for the treatment of muscular
      dystrophies (MD). The review covers literature from the past 2 - 3 years. WHAT
      THE READER WILL GAIN: rAAV-directed muscular dystrophy gene therapy can be
      achieved by mini-dystrophin replacement and exon-skipping strategies. The
      additional strategies of enhancing muscle regeneration and reducing inflammation
      in the muscle micro-environment should be useful to optimize therapeutic
      efficacy. This review compares the merits and shortcomings of different
      administration methods, promoters and experimental animals that will guide the
      choice of the appropriate strategy for clinical trials. TAKE HOME MESSAGE:
      Restoration of muscle histopathology and function has been performed using rAAV
      systemic gene delivery. In addition, the combination of gene replacement and
      adjuvant therapies in the future may be beneficial with regard to improving
      muscle regeneration and decreasing myofiber necrosis. The challenges faced by
      large animal model studies and in human trials arise from gene transfer
      efficiency and immune response, which may be overcome by optimizing the rAAV
      vectors utilized and the administration methods.

PMID- 20132061
TI  - Towards organ printing: engineering an intra-organ branched vascular tree.
AB  - IMPORTANCE OF THE FIELD: Effective vascularization of thick three-dimensional
      engineered tissue constructs is a problem in tissue engineering. As in native
      organs, a tissue-engineered intra-organ vascular tree must be comprised of a
      network of hierarchically branched vascular segments. Despite this requirement,
      current tissue-engineering efforts are still focused predominantly on engineering
      either large-diameter macrovessels or microvascular networks. AREAS COVERED IN
      THIS REVIEW: We present the emerging concept of organ printing or robotic
      additive biofabrication of an intra-organ branched vascular tree, based on the
      ability of vascular tissue spheroids to undergo self-assembly. WHAT THE READER
      WILL GAIN: The feasibility and challenges of this robotic biofabrication approach
      to intra-organ vascularization for tissue engineering based on organ-printing
      technology using self-assembling vascular tissue spheroids including clinically
      relevantly vascular cell sources are analyzed. TAKE HOME MESSAGE: It is not
      possible to engineer 3D thick tissue or organ constructs without effective
      vascularization. An effective intra-organ vascular system cannot be built by the
      simple connection of large-diameter vessels and microvessels. Successful
      engineering of functional human organs suitable for surgical implantation will
      require concomitant engineering of a 'built in' intra-organ branched vascular
      system. Organ printing enables biofabrication of human organ constructs with a
      'built in' intra-organ branched vascular tree.

PMID- 20132062
TI  - HPV vaccine: Cervarix.
AB  - IMPORTANCE OF THE FIELD: Cervical cancer is a major cause of morbidity and
      mortality worldwide and is common in relatively young women. Cervical screening
      programs, while successful if properly carried out, are difficult and expensive
      to implement, and offer secondary, not primary prevention. Vaccination against
      the human papillomavirus (HPV), which is the major cause of cervical cancer, is a
      significant step forward. AREAS COVERED IN THIS REVIEW: The data on Cervarix, the
      GSK HPV vaccine, are reviewed and placed in the context of HPV vaccination as a
      whole. A literature review using PubMed listed publications and official product
      websites has been carried out. WHAT THE READER WILL GAIN: The reader will gain an
      understanding of the issues involved in HPV vaccination and of the data to date.
      TAKE HOME MESSAGE: Cervarix has been shown to have high efficacy against disease
      associated with both HPV-16 and HPV-18. Its antibody response profile allows for
      optimism regarding the duration of immunity. The fact that it is a virus-like
      particle, rather than a live-virus vaccine, is reassuring regarding safety, as
      are the reasonably extensive safety data for the vaccine preparation so far
      accrued. Cross protection against oncogenic non-vaccine HPV types, in particular
      HPV-45, may be important in the prevention of cervical adenocarcinoma, which is
      currently not well served by screening.

PMID- 20132063
TI  - Enhancing adoptive immunotherapy of cancer.
AB  - IMPORTANCE OF THE FIELD: Conventional therapies, including surgery, chemotherapy
      and radiotherapy have contributed much to cancer treatment. However, these
      treatment modalities fail in a large proportion of patients, and there is a great
      need for effective alternate therapies. Adoptive immunotherapy can be effective
      against some cancers that have failed all other treatment options, even when
      disease burdens are massive. AREAS COVERED IN THIS REVIEW: This review gives a
      brief introduction of the historical origins of adoptive immunotherapy and then
      provides details of strategies for increasing the potency of cell transfer.
      Approaches for enhancing adoptive immunotherapy include: selecting the right type
      of cell; providing cytokine support; preconditioning patients and tuning the
      tumor microenvironment. The review also provides insights into the safety,
      feasibility and costs of this form of therapy. WHAT THE READER WILL GAIN: This
      article will give the reader an appreciation of the potential of adoptive
      immunotherapy, as well as an understanding of some limitations and current
      approaches for optimizing the effectiveness of this approach. TAKE HOME MESSAGE:
      With recent developments in knowledge of the interactions between the immune
      system and tumors, the field of adoptive immunotherapy is now poised to make
      dramatic contributions to cancer therapy.

PMID- 20132064
TI  - Autologous stem cell transplantation in autoimmune and rheumatic diseases: from
      the molecular background to clinical applications.
AB  - Autoimmune diseases have a multifactorial origin. Because of disturbances of the
      immune system, autoreactive T and B cells target self-antigens, leading to
      permanent organ damage. Despite novel therapeutic protocols, the disease course
      is chronic and in many instances the outcome is lethal. The efficacy of stem cell
      therapy has been observed in autoimmune animal models and in autoimmune diseases
      related to haematological abnormalities. Although the therapy is more than 30
      years old, its broad spread has been delayed by the serious side-effects due to
      the conditioning treatments based on oncological protocols. Evaluation of the
      data of patients who have undergone autologous stem cell therapy reinforced the
      view that protocols used for conditioning treatments, mostly causing
      lymphoablation, and procedures carried out in specialist centres significantly
      reduced mortality, with an almost optimal therapeutical efficacy. New,
      multicentre investigations have been launched to compare the efficacy of various
      protocols. In this review, we summarize certain aspects of the molecular
      background of autologous stem cell transplantation and also depict the response
      to therapy in various autoimmune and rheumatic diseases.

PMID- 20132065
TI  - Can disease-modifying anti-rheumatic drugs be discontinued in long-standing
      rheumatoid arthritis? A 15-year follow-up.
AB  - OBJECTIVE: To investigate the 15-year outcome of patients with early rheumatoid
      arthritis (ERA) with respect to the continuity of treatment. METHODS: We
      conducted a 15-year follow-up study of 87 patients with ERA treated since
      diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) according to the
      'sawtooth' strategy. The patients were divided into groups according to the
      continuity of treatment: (A) 'continuous DMARDs', (B) 'discontinued and restarted
      DMARDs', and (C) 'permanently discontinued DMARDs'. The main outcome measurements
      included the Health Assessment Questionnaire (HAQ), the Larsen score, and
      clinical remission according to the American Rheumatism Association (ARA)
      criteria. RESULTS: Seventy (80%) patients participated in the 15-year follow-up.
      DMARDs were discontinued in 20 (29%) patients due either to remission or to a
      symptom-free period of the disease. The disease flared up in nine (45%) of these
      patients, in some patients several years after the discontinuation. At the 15
      year follow-up, 59 (84%) patients were on DMARDs; only three (4%) were using
      biologicals. Functional capacity remained good in all groups (mean HAQ score
      0.52). The mean Larsen score was higher (54) in group A than in groups B (25) and
      C (12) (p =0.001). The remission rate was 64% in group C and considerably lower
      in groups A (6%) and B (0%) (p<0.001). CONCLUSIONS: Our results indicate that
      most of the patients with long-standing RA require continuous DMARD treatment. If
      the treatment is discontinued, patients should be followed-up closely and DMARDs
      readministered without delay if the disease flares up.

PMID- 20132066
TI  - Time to methotrexate treatment in patients with rheumatoid arthritis referred to
      hospital.
AB  - OBJECTIVE: To describe time to methotrexate (MTX) treatment among patients with a
      first-time diagnosis of rheumatoid arthritis (RA) in a hospital-based department
      of rheumatology. METHODS: Using prescription data, we conducted a large cohort
      study in the County of Aarhus, Denmark, including all patients with a first-time
      diagnosis of RA. We used Kaplan-Meier estimates to compute the cumulative
      probability of MTX treatment start with follow-up starting on the date of
      referral. We defined early treatment start as MTX initiation within 90 days after
      referral. RESULTS: Among 1516 RA patients, a total of 703 (46%) started MTX
      treatment during the study period. The overall median time to treatment start was
      120 days [interquartile range (IQR) 19-557]. Patients included in 2000-2006 had
      an earlier MTX treatment start compared with patients included in 1996-1999
      [adjusted incidence rate ratio (IRR) 1.83, 95% confidence interval (CI) 1.55
      2.16]. Patients with a C-reactive protein (CRP) level>300 nmol/L had an earlier
      MTX treatment start compared with patients with a moderate CRP level (adjusted
      IRR 1.36, 95% CI 1.16-1.73). Only 21% of the patients started MTX within 90 days
      after referral and those were mainly patients included in later years and
      patients with a high CRP. CONCLUSIONS: The data suggest that reduction in the
      time to start MTX treatment after referral to hospital could be improved,
      especially among patients with less severe symptoms. However, our results show
      that treatment practice in recent years has changed towards an earlier MTX
      treatment start.

PMID- 20132067
TI  - Expression analysis of Notch-related molecules in peripheral blood T helper cells
      of patients with rheumatoid arthritis.
AB  - OBJECTIVE: Expression of Notch homologues in local tissue inflammation in
      rheumatoid arthritis (RA) and cultured synoviocytes has been reported, but the
      expression profile of Notch-related molecules in peripheral lymphocytes in RA
      remains unclear. In this study, we measured the expression of Notch receptors and
      downstream molecules in peripheral lymphocytes from RA patients. METHODS:
      Expression of Notch receptors in peripheral lymphocytes of RA patients was
      assessed by both flow cytometry and real-time polymerase chain reaction (PCR).
      Expression of the representative Notch target gene HES-1 and the regulatory gene
      NUMB in purified T helper cells from RA patients was determined by real-time PCR,
      and expression of Notch intracellular domain (ICD) was determined by immunoblot
      analysis. RESULTS: There was an increased expression of Notch 2, Notch 3, and
      Notch 4 in T helper cells from active RA patients, among which increased
      expression of Notch 3 was mainly by activated T cells. Notably, expression of
      Notch 3 in T cells decreased in inactive RA patients and the level was similar to
      that of healthy controls (HC). Notch receptors were rarely observed on B cells
      and no difference in expression was found between RA patients and HC. T helper
      cells from RA patients exhibited increased expression of the target gene HES-1
      but decreased expression of the negative modulation gene NUMB of Notch
      signalling. There was also an increased nuclear translocation of Notch-ICD in T
      helper cells from active RA disease. CONCLUSION: The present study demonstrated
      that T helper cells from RA patients display a significantly altered expression
      profile of Notch receptors and enhanced activation of Notch signalling compared
      with HC.

PMID- 20132068
TI  - Cystatin C is a sensitive marker for detecting a reduced glomerular filtration
      rate when assessing chronic kidney disease in patients with rheumatoid arthritis
      and secondary amyloidosis.
AB  - OBJECTIVE: Chronic kidney disease is a predictor of end-stage renal disease, and
      evaluating the glomerular filtration rate (GFR) is necessary to make a definite
      diagnosis. We assessed the utility of serum cystatin C (cysC) for identifying a
      reduced GFR in patients who have rheumatoid arthritis (RA) with secondary
      amyloidosis. METHODS: Fifty patients with RA and secondary amyloidosis (mean age
      60.9+/-11.2 years; 45 women) were evaluated. The revised 24-h creatinine
      clearance (r24-hC(Cr)), which was determined by multiplying the original value by
      0.719, was used as a reference for the GFR. The screening potential of the serum
      cysC and some estimates of the GFR calculated from the serum cysC (cysC-eGFR:
      eGFR(Hoek) and eGFR(Rule)) for detecting a reduced GFR (r24-hC(Cr)<60 mL/min/1.73
      m(2)) were analysed. RESULTS: Both cysC-eGFRs were strongly correlated with the
      r24-hC(Cr) (eGFR(Hoek), r=0.846, p<0.001; eGFR(Rule), r=0.820, p<0.001). The
      difference between the average eGFR(Rule) (37.1+/-31.2 mL/min/1.73m(2)) and
      average r24-hC(Cr) (35.3+/-30.9 mL/min/1.73 m(2)) was small, whereas eGFR(Hoek)
      and sCr-eGFR were higher than eGFR(Rule) and r24-hC(Cr). In receiver operating
      characteristic (ROC) curve analyses of a reduced GFR, serum cysC gave a greater
      area under the curve (AUC=0.958) than the sCr-eGFR (0.939-0.942). The specificity
      and positive predictive value (PPV) reached 100% when serum cysC >1.365 mg/L was
      used. CONCLUSIONS: Serum cysC can identify a reduced GFR more accurately than sCr
      eGFRs. Serum cysC >1.09 mg/L (i.e. eGFR(Rule)<60 mL/min/1.73 m(2)) could be a
      marker of a reduced GFR, and serum cysC >1.365 mg/L would strongly suggest a
      reduced GFR in patients who have RA with secondary amyloidosis.

PMID- 20132069
TI  - The relationship between disease-related characteristics and conduction
      disturbances in ankylosing spondylitis.
AB  - OBJECTIVES: Ankylosing spondylitis (AS) is associated with an increased
      cardiovascular (CV) risk. Conduction disturbances (CD) may explain the CV burden,
      as they are independently associated with cardiac disease. The aim of this study
      was (i) to determine the prevalence of CD in AS, and (ii) to evaluate the
      relationship between CD and demographic and AS-related characteristics. METHODS:
      A rheumatological evaluation assessing demographic and AS-related characteristics
      and a resting standard 12-lead electrocardiogram (ECG) were performed in 131
      consecutive AS patients. RESULTS: A first-degree atrioventricular (AV) block was
      found in six (4.6%) patients. One (0.8%) patient suffered from a complete right
      bundle branch block (RBBB) and one (0.8%) patient had a left anterior hemiblock.
      A prolonged QRS (pQRS) interval was observed in 38 (29.2%) patients, including
      those with a complete or incomplete BBB. Age, disease duration, and body mass
      index (BMI) were significantly associated with the PR interval, and male gender,
      disease duration, and the Bath Ankylosing Spondylitis Metrology Index (BASMI)
      with the QRS interval. In multivariate analyses, disease duration remained
      independently associated with both the PR and the QRS intervals. CONCLUSION:
      Intraventricular CD is highly prevalent in AS, particularly in patients with long
      standing disease. Further research is needed to determine whether
      intraventricular CD contribute to the increased CV risk and long-term CV
      mortality in AS.

PMID- 20132070
TI  - Metabolic syndrome, endothelial injury, and subclinical atherosclerosis in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVES: To study the link between metabolic syndrome (MetS), endothelial
      injury, and atherosclerosis in patients with systemic lupus erythematosus (SLE).
      METHODS: Consecutive SLE patients without a history of arterial thrombosis were
      screened for atherosclerosis at the carotid and coronary arteries by B-mode
      ultrasound [intima-media thickness (IMT)] and multidetector computed tomography
      (MDCT) scan (Agatston calcium scores), respectively. Plasma levels of
      homocysteine, high-sensitivity C-reactive protein (hsCRP), soluble vascular cell
      adhesion molecule (sVCAM)-1, P-selectin, and soluble thrombomodulin (sTM) were
      assayed. Patients were stratified according to the National Cholesterol Education
      Program (NCEP) Adult Treatment Panel III (ATP III) criteria for MetS, using the
      Asian criteria for abdominal obesity. Risk factors for atherosclerosis were
      studied. RESULTS: Of the 123 SLE patients (93% women; age 47.9+/-11 years; SLE
      duration 10.9+/-7.0 years) studied, 20 (16.3%) had MetS. The prevalence of MetS
      in the SLE patients was significantly higher than in 492 age- and sex-matched
      healthy controls (9.6%; p=0.03). Coronary calcification and abnormal carotid IMT
      were detected in 38 (31%) and 72 (59%) of SLE patients, respectively. Patients
      with MetS had a significantly higher Agatston score (69.5+/-95 vs. 16.4+/-57;
      p=0.03) and a numerically higher carotid IMT (p=0.43) than those without. In a
      logistic regression model, the MetS [odds ratio (OR) 3.11, 95% confidence
      interval (CI) 1.01-9.59, p=0.049] was associated with coronary atherosclerosis
      after adjustment for age and other risk factors. In addition, patients with MetS
      had significantly higher levels of hsCRP (p=0.002), homocysteine (p=0.03), and
      sTM (p=0.01). CONCLUSIONS: The MetS is more prevalent in SLE patients than the
      general population and is associated with endothelial injury and coronary
      atherosclerosis. More aggressive control of risk factors is justified in these
      patients.

PMID- 20132071
TI  - Anti-CD43 and anti-galectin-1 autoantibodies in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) is characterized by the production
      of multiple autoantibodies and also by T-cell dysfunction. CD43 is expressed by
      most immune cells, is involved in lymphocyte adhesion and activation, and
      interacts with galectin-1 (Gal-1). The aim of this work was to evaluate the
      plasma levels of autoantibodies against CD43 and Gal-1 as well as the levels of
      soluble Gal-1 in SLE Mexican mestizo patients, with the aim of establishing a
      correlation between these parameters and the clinical profile. METHODS: Serum
      levels of immunoglobulin (Ig)G autoantibodies against CD43 and Gal-1 and levels
      of soluble Gal-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 55
      patients with SLE and 71 healthy controls. RESULTS: We found significantly
      enhanced titres of anti-CD43 and anti-Gal-1 antibodies in sera from SLE patients
      compared to controls. In addition, the serum levels of Gal-1 were significantly
      higher in SLE patients than in healthy individuals. However, we could detect no
      correlation of these parameters with disease activity [using the Mexican Systemic
      Lupus Erythematosus Disease Activity Index (MEX-SLEDAI)], age, or a variety of
      different clinical or laboratory features. Similarly, no significant correlation
      with immunosuppressive or glucocorticoid therapy was observed. By contrast, a
      significant association was found between anti-CD43 titres and time of disease
      evolution, complement levels, and the presence of anti-Gal-1 antibodies.
      CONCLUSIONS: As CD43 and Gal-1 participate in modulating the immune system, we
      suggest that the presence of autoantibodies against these molecules may
      contribute to the immune deregulation observed in SLE.

PMID- 20132072
TI  - Health-related quality of life in systemic lupus erythematosus and its
      association with disease and work disability.
AB  - OBJECTIVES: To determine the health-related quality of life (HRQOL) and its
      relationship to disease variables, vertebral fractures, and employment status in
      female patients with systemic lupus erythematosus (SLE). METHODS: HRQOL was
      assessed with the Swedish version of the Medical Outcomes Study (MOS) 36-Item
      Short Form Survey (SF-36) in female patients (n=163) and in age- and sex-matched
      controls (n=1045). Associations between the SF-36 score and demographics, disease
      variables, prevalent vertebral fractures, and employment status were analysed.
      RESULTS: The SLE patients, aged 20 to 82 years, scored significantly lower than
      the controls on all SF-36 subscales. Patients with vertebral fractures were
      older, had greater disease damage, and lower physical functioning (PF) than
      patients without fractures. Of the SLE patients of working age (n=142), 54%
      worked full or part time. These patients scored their HRQOL significantly higher
      (better) than patients not working. Being able to work was significantly
      associated with low age and high scores in PF and role physical (RP): the area
      under the receiver operating characteristic (ROC) curve for these variables was
      0.82, confidence interval 0.75-0.89. CONCLUSIONS: HRQOL is substantially lower in
      SLE than in the general population but working ability indicates better health.
      We encourage further research regarding the effects on HRQOL by preventive
      actions taken against work disability in SLE.

PMID- 20132073
TI  - Exercise in systemic sclerosis intensifies systemic inflammation and oxidative
      stress.
AB  - OBJECTIVE: Exercise testing can be used (i) to evaluate functional limitations of
      systemic sclerosis (SSc) and (ii) to study whether the inflammatory and oxidative
      systems are activated after a physical stimulus. The aim of this study was to
      determine exercise-induced inflammatory and oxidative responses in SSc compared
      with healthy subjects. METHODS: Eleven patients with SSc and pulmonary
      involvement and 10 healthy subjects underwent maximal cardiopulmonary exercise
      testing (CPET). Physiological responses were followed continuously during
      cycling. Blood samples were taken at rest, during and after maximal exercise to
      measure inflammatory and oxidative markers. RESULTS: In nine of the 11 SSc
      patients, cardiocirculatory limitation and gas exchange impairment limited
      exercise capacity. Basal inflammatory cells, interleukin (IL)-6, and oxidative
      stress were increased in SSc compared to healthy subjects and intensified after
      exercise. Basal and exercise-induced inflammation and oxidative stress were
      correlated with the modified Rodnan skin score. CONCLUSIONS: Although exercise
      capacity is impaired in patients with SSc, physical activity intensifies the
      already increased basal levels of systemic inflammation and oxidative stress.
      These data support the concept of a role for systemic inflammation and oxidative
      stress in the ongoing systemic effects of SSc.

PMID- 20132074
TI  - Survival of patients with Wegener's granulomatosis diagnosed in Finland in 1981
      2000.
AB  - OBJECTIVE: To determine the survival of and contributing factors in patients
      diagnosed with Wegener's granulomatosis (WG) between 1981 and 2000 in Finland.
      METHODS: A retrospective cohort study using hospital discharge registers with a
      review of hospital case records. Analysis of causes of death in Finland up to 30
      July 2005. RESULTS: A total of 492 patients received a verified diagnosis of WG
      between 1981 and 2000. Of these, 203 died before the end of June 2005. The
      overall 1-year survival rate was 83.3% and the 5-year survival rate was 74.2%.
      The standardized mortality ratio (SMR) for all WG patients was 3.43 [95%
      confidence interval (CI) 2.98-3.94], for women 4.38 (95% CI 3.59-5.61) and for
      men 2.80 (95% CI 2.28-3.41). The most frequent causes of death were WG or another
      connective tissue disease, cardiovascular events and neoplasms. The prognosis did
      not change markedly over the 20-year period. Older age and elevated creatinine
      level at presentation were associated with poorer prognosis, whereas primary ear,
      nose, and throat (ENT) involvement and prompt treatment with cyclophosphamide
      predicted longer survival. CONCLUSIONS: WG patients had increased mortality
      compared with the rest of the population. Older age and elevated creatinine level
      at diagnosis predicted poor prognosis, but ENT involvement initially and
      cyclophosphamide treatment resulted in a better outcome.

PMID- 20132075
TI  - Effects of anti-cardiolipin antibodies and IVIg on annexin A5 binding to
      endothelial cells: implications for cardiovascular disease.
AB  - OBJECTIVES: Anti-phospholipid antibodies (aPL), including anti-cardiolipin
      antibodies (aCL), are risk factors for cardiovascular disease (CVD) in the
      general population and in patients with the anti-phospholipid syndrome (APS;
      Hughes syndrome). APS may be primary but is also common in patients with systemic
      lupus erythematosus (SLE). The anti-coagulant protein annexin A5 (ANXA5) is
      implicated in CVD by interfering with phospholipids and aPL. METHODS: ANXA5
      binding to human umbilical venous endothelial cells (HUVECs) was determined by
      flow cytometry. RESULTS: When cells were cultured in serum from APS patients with
      a high aPL titre (aPL-S), binding of ANXA5 to HUVECs was reduced. Monoclonal
      immunoglobulin (Ig)G aPL against cardiolipin (mAb-CL) dose-dependently reduced
      ANXA5 binding to endothelium. Preincubation of intravenous (IV)Ig at
      therapeutically relevant doses with aPL-S and mAb-aCL restored ANXA5 binding to
      comparable levels when normal healthy serum (NHS) was used. By contrast, IVIg per
      se had the capacity to reduce ANXA5 binding to endothelium when added to NHS (but
      not to aPL-S). CONCLUSIONS: Decreased ANXA5 binding to endothelium, mediated by
      aPL, is a novel mechanism of atherothrombosis that can be countered by IVIg in
      vitro. IVIg per se could, to a lesser degree, cause decreased ANXA5 binding in
      NHS, which raises the possibility that some antibodies in IVIg can be involved in
      a side-effect reported in IVIg treatment, namely atherothrombosis and CVD.
      Increasing ANXA5 binding, either by addition of ANXA5 or by use of neutralizing
      antibodies in IVIg, represents a possible therapeutic strategy that deserves
      further study.

PMID- 20132076
TI  - Hand osteoarthritis and pinch grip strength among middle-aged female dentists and
      teachers.
AB  - OBJECTIVES: Among female dentists and teachers, we investigated the relationship
      of pinch grip strength with radiographic hand osteoarthritis (OA) and hand joint
      pain. MATERIALS AND METHODS: We studied 295 female dentists and 248 female
      teachers aged 45-63 years for pinch grip strength using the Martin Vigorimeter.
      Hand radiographs were examined for the presence of OA in the wrist and each joint
      of the first, second, and third fingers. Joint pain and tasks with high hand
      loading during leisure were assessed by questionnaire. Glove size was used as
      proxy for hand size. RESULTS: Symptomatic hand OA (jointwise co-occurrence of
      radiological findings and pain) increased the risk of low pinch grip strength in
      both hands, with an odds ratio (OR) of 3.3 (95% CI 1.8-6.2) for the right and 2.0
      (95% CI 1.1-3.8) for the left hand, allowing for age, occupation, body mass index
      (BMI), hand size, and hand-loading leisure-time activity. The occurrence of
      findings and pain in non-corresponding joints was also associated with pinch grip
      strength in the right hand, but not in the left. Having only radiographic
      findings or pain was not associated with pinch grip strength. CONCLUSIONS: Our
      findings support the view that hand function is related to the severity of hand
      OA.

PMID- 20132077
TI  - Successful autologous stem cell transplantation in two patients with juvenile
      dermatomyositis.
AB  - Juvenile dermatomyositis (JDM) is a chronic inflammatory disorder of unknown
      aetiology that affects muscle and skin. We report on two patients with severe
      progressive JDM who developed contractures and were wheelchair dependent despite
      therapy including methotrexate (MTX), steroids, immunoglobulins, cyclosporin A,
      and rituximab. On account of the refractory disease, autologous stem cell
      transplantation (ASCT) was performed using a CD3/CD19-depleted graft after
      immunoablative conditioning with fludarabine, cyclophosphamide, and anti
      thymocyte globulin. This induced a dramatic improvement and sustained remission
      of the disease in both patients. We demonstrate that ASCT is a therapeutic option
      with low toxicity for patients with severe, refractory JDM.

PMID- 20132078
TI  - Tophaceous gout: an unusual cause of multiple fractures.
AB  - OBJECTIVE: Fractures occurring at the site of a tophus have rarely been described
      in gout. In this paper we review the occurrence, clinical features, and outcome
      of fractures in tophaceous gout. METHOD: A PubMed search was conducted to
      identify the relevant literature, following our experience with two patients who
      developed tophaceous fractures after minor or no trauma. RESULTS: A total of 13
      patients were analysed. Eleven cases of tophaceous fracture have been reported
      since 1950. Common features are: known and long-standing gout with tophi; minor
      or absence of trauma; specific locations include seven patients with patella bone
      fractures. Other sites include the cervical spine in two patients, the first and
      fifth metatarsal, and a phalanx in one patient each, the ilium and pubic bones in
      one, the medial malleola, and the femoral neck in the latter case. CONCLUSIONS:
      Monosodium urate (MSU) crystals can contribute to bone lesions by reducing
      osteoblastic activity and are associated with enhanced osteoclast activity in the
      vicinity of tophi. Mild trauma triggers MSU crystal release from tophi, resulting
      in cell activation and production of cytokines and proteases. This could enhance
      bone erosion leading ultimately to bone fragility and fracture. Our cases
      exemplify a rare cause of spontaneous fracture. Gouty tophus should be considered
      when facing a lytic lesion with fracture.

PMID- 20132079
TI  - Trough infliximab concentration may predict long-term maintenance of infliximab
      in ankylosing spondylitis.

PMID- 20132080
TI  - Fish consumption by traditional subsistence villagers of the Rio Madeira
      (Amazon): impact on hair mercury.
AB  - BACKGROUND: Subsistence ribeirinhos of the Amazon Basin depend on fish for their
      principal source of protein, but fish availability changes with seasonal high and
      low waters. AIM: To assess taxa and quantity of fish consumed and estimate
      attendant exposure to methyl-Hg in a traditional subsistence high fish-eating
      community of the Amazon Basin. SUBJECTS AND METHODS: 120 villagers in 18
      households were followed for 6 months (August to February) for weighed portions
      of fish consumed. RESULTS: Mean daily per capita fish consumption was high (406
      g/day) with fish meals ranging from 4 to 14 times/week and an integrated yearly
      consumption of 148.2 kg/person. Median total-Hg concentrations in fish ranged
      from 0.011 to 0.409 ppm; six of the more consumed fish species comprised more
      than 50% of the fish consumed. The villagers mean hair-Hg concentration was high
      (17.4 +/- 11.5 microg/g), with both inter- and intra-household variation despite
      similar high fish consumption; only 7% showed hair-Hg concentrations < 5
      microg/g, but 75% had hair-Hg levels above 10 microg/g. Maternal hair-Hg was
      significantly correlated with respective children's hair-Hg (Spearman r = 0.5390;
      p < 0.0001). The high daily fish intake of these villagers is predominantly of
      species with much lower Hg concentrations. CONCLUSION: In Amazonian lifestyle of
      ribeirinho communities traditional fish consumption is high and depends on
      available species; fish is also the principal via of meHg exposure and attendant
      hair-Hg concentrations.

PMID- 20132081
TI  - Cerebrospinal fluid human immunodeficiency virus viral load in patients with
      neurosyphilis.
AB  - Syphilis is a frequent coinfection with human immunodeficiency virus (HIV).
      Whereas systemic syphilis infection increases plasma HIV RNA levels (viral load;
      VL), effects of syphilis on cerebrospinal fluid (CSF) VL are unknown. We
      hypothesized that intrathecal immune activation in neurosyphilis would
      selectively increase CSF VL in coinfected patients. In this study, HIV-infected
      research subjects (N = 225) were categorized into three groups based on serum
      rapid plasma reagin (RPR), microhemaglutination for Treponema pallidum (MHA-TP)
      MHA-TP, and CSF VDRL: 23 with neurosyphilis (NS+; reactive serum RPR and MHA-TP
      and positive CSF VDRL); 42 with systemic syphilis but not neurosyphilis (Syph+;
      reactive serum RPR and MHA-TP; negative CSF VDRL), and 160 without syphilis (Syph
      ; nonreactive serum RPR). Plasma and CSF HIV VL were quantified by reverse
      transcriptase-ploymerase chain reaction (RT-PCR) (Amplicor, Roche) in log(10)
      copies/ml. To adjust for covariates previously shown to influence CSF HIV VL
      (i.e., plasma VL, CD4, pleocytosis, and highly active antiretroviral therapy
      [HAART]), multivariable linear regression was used. Lumbar punctures (LP) done
      for research purposes diagnosed 23 with neurosyphilis; most (83%) of these
      reported prior syphilis treatment. Among subjects with detectable plasma VL, CSF
      VL was highest in NS+, followed by Syph+ and Syph- (P =.006). This relationship
      was independent of the level of plasma VL or CSF pleocytosis. By contrast, among
      subjects with undetectable plasma HIV VL, CSF VLs were similar in the three
      syphilis subgroups (P = .50). Neurosyphilis may amplify intrathecal HIV
      replication, possibly through immune activation that persists even after syphilis
      treatment. Because elevated CSF VL is associated with subsequent neurocognitive
      decline, future studies should evaluate the impact of neurosyphilis on the course
      of central nervous system (CNS) HIV infection.

PMID- 20132082
TI  - Comparison of magnetic resonance imaging and video capsule enteroscopy in
      diagnosing small-bowel pathology: localization-dependent diagnostic yield.
AB  - OBJECTIVE: New technology has considerably advanced the diagnosis of small-bowel
      pathology. However, its significance in clinical algorithms has not yet been
      fully assessed. The aim of the present analysis was to compare the diagnostic
      utility and yield of video-capsule enteroscopy (VCE) to that of magnetic
      resonance imaging (MRI) in patients with suspected or established Crohn's disease
      (Group I), obscure gastrointestinal blood loss (Group II), or suspected tumors
      (Group III). MATERIAL AND METHODS: Forty-six out of 182 patients who underwent
      both modalities were included: 21 in Group I, 20 in Group II, and five in Group
      III. Pathology was assessed in three predetermined sections of the small bowel
      (upper, middle, and lower). The McNemar and Wilcoxon tests were used for
      statistical analysis. RESULTS: In Group I, lesions were found by VCE in nine of
      the 21 patients and by MRI in six. In five patients, both modalities showed
      pathology. In Group II, pathological changes were detected in 11 of the 20
      patients by VCE and in eight patients by MRI. In five cases, pathology was found
      with both modalities. In Group III, neither modality showed small-bowel
      pathology. For the patient groups combined, diagnostic yield was 43% with VCE and
      30% with MRI. The diagnostic yield of VCE was superior to that of MRI in the
      upper small bowel in both Groups I and II. CONCLUSION: VCE is superior to MRI for
      the detection of lesions related to Crohn's disease or obscure gastrointestinal
      bleeding in the upper small bowel.

PMID- 20132083
TI  - Regeneration associated growth factor receptor and epithelial marker expression
      in lymphoid aggregates of ulcerative colitis.
AB  - OBJECTIVE: Mesenchymal-epithelial transition may have crucial role in mucosal
      regeneration, hence we assayed epithelial growth factor receptor (EGFR), insulin
      like growth factor receptor-1 (IGF1R), hepatocyte-derived growth factor receptor
      (HGFR), CDX2 and cytokeratin (CK) expression in lymphoid aggregates (LA) of
      ulcerative colitis (UC). MATERIAL AND METHODS: Tissue microarrays (TMAs) made of
      biopsy samples from 20 mildly, 20 moderately and 20 severely active UC, 12 non
      specific colitis (NSC) and 20 healthy colon were prepared, and immunolabelled
      with anti-EGFR, -IGF1R, -HGFR, -CDX2, -CK antibodies. After virtual microscopic
      evaluation, one-way ANOVA and correlation analysis were performed. For
      validation, TaqMan real-time RT-PCR was performed by using RNA from laser
      microdissected LA from 10 healthy colon and 10 endoscopically active UC biopsies.
      RESULTS: The number of LA was in tight positive correlation with the severity of
      inflammation (r=0.9). The number of EGFR/HGFR positive subepithelial cells was
      found to be significantly elevated in severe (21.6+/-2.1%/21.3+/-1.9%), moderate
      (14.3+/-1.7%/14.6+/-1.6%) and mild (7.2+/-1.6%/7.4+/-1.3%) inflammation compared
      to healthy colon mucosa (2.6+/-1.4%/2.4+/-1.03%) (p < 0.005). Some alterations
      were found between UC and NSC samples regarding EGFR and HGFR expression. IGF1R
      immunoreactive cells were only found in a trace number in all cases. Increasing
      trend of CDX2 and CK positive subepithelial cells was found in active UC, but it
      was not in significant correlation with the severity of inflammation. CONCLUSION:
      EGFR and HGFR positive subepithelial cells in LA may be involved in the induction
      of the regenerative mucosal processes. The presence of CDX2/CK positive
      subepithelial cells suggests that mesenchymal-to-epithelial transition may be
      located to lymphoid aggregates.

PMID- 20132084
TI  - The clinical course of progressive bulbar palsy.
AB  - Our objective was to study the clinical course of patients diagnosed with
      progressive bulbar palsy (PBP). We reviewed all 392 medical records of ALS
      patients seen between 1 January 2000 and 31 July 2007. Patients with isolated PBP
      at presentation were selected and classified into those with normal EMG of the
      limbs (PBP-N) and those with active denervation on EMG (PBP-A). We studied the
      time to progression of these patients to ALS. We compared patients with PBP-N to
      patients with PBP-A. Fifteen patients were diagnosed with PBP-N. The remaining 17
      had PBP-A. Thirteen of the 15 patients with PBP-N (87%) progressed to definite
      ALS. The two patients who did not progress to ALS died at 22 and 60 months,
      respectively. The median survival time was 35 months for the PBP-N group and 40
      months for the PBP-A group (p = 0.92). Except for the rate of depression,
      patients with PBP-N did not differ from patients with PBP-A in the basic
      demographics, time of presentation, clinical course, survival and treatment
      received. All patients with FTD died within 40 months of onset of symptoms. In
      conclusion, almost all PBP patients progress to ALS regardless of the presence of
      upper motor signs or generalized denervation on EMG of the limbs.

PMID- 20132085
TI  - A pilot study of the prevalence of psychiatric disorders in PLS and ALS.
AB  - The prevalence of psychiatric disorders in primary lateral sclerosis (PLS) is
      currently unknown. In the present study, we compared the prevalence of
      psychiatric illness in patients with PLS and amyotrophic lateral sclerosis (ALS).
      We hypothesized that if the psychosocial stress of motor neuron disease
      predisposes patients to depressive disorders, patients with ALS (with a poorer
      prognosis and more disability than patients with PLS) should have a higher
      prevalence of depressive disorders than patients with PLS. We administered the
      gold standard of psychiatric assessment, the SCID, to 19 PLS and 13 ALS patients.
      We found a prevalence of current depressive disorders in PLS patients that was,
      by a non-significant trend, lower than that of ALS patients. The prevalence of
      current depressive disorders in the ALS patients was higher than previously
      reported and similar to that observed in non-neurological medical disorders.
      Other psychiatric disorders were rare. In conclusion, depressive disorders were
      the most commonly observed psychiatric disorders in both PLS and ALS. By a non
      significant trend, the PLS patients had a lower current prevalence of depressive
      disorders than the ALS patients. These data are consistent with the hypothesis
      that the psychosocial stress of MND is a risk factor for depression.

PMID- 20132086
TI  - Sperm DNA fragmentation assessment: is it really helpful?

PMID- 20132087
TI  - Effect of pituitary growth hormone and insulin-like growth factor type-I on
      proliferation, apoptosis and hormone secretion of the placental cell line JEG-3.
AB  - OBJECTIVE: Placenta human choriocarcinoma JEG-3 cells were used to study the
      possibility that pituitary growth hormone (GH) and insulin-like growth factor
      type I (IGF-I) act on first trimester of pregnancy progesterone (P4) and human
      chorionic gonadotropin (hCG) secretion, cell proliferation and apoptosis.
      MATERIAL AND METHODS: The JEG-3 cell line was cultured in Dulbecco modified eagle
      medium without phenol red containing 10% FBS. The cells were plated in 96-well
      plates at the density of 3 x 10(3) for 24 h and treated with 10, 50, 100, or 200
      ng/ml of GH or 10, 30, 100, or 250 ng/ml of IGF-I for 24 h. At the end of the
      culture period, cell proliferation was measured using the BrdU colorimetric assay
      and caspase-3 activity, as a marker of apoptosis, was determined by the
      colorimetric method. Media were frozen for hormone analysis by enzyme
      immunoassay. Results. We found that the stimulatory activities of GH and IGF-I on
      both P4 and hCG secretion paralleled the stimulation of cell proliferation and
      inhibition of apoptosis. CONCLUSION: Our findings suggest an important role for
      pituitary GH and IGF-I in normal placental function during the first trimester of
      pregnancy.

PMID- 20132088
TI  - Upper limb neuropathy such as carpal tunnel syndrome as an initial manifestation
      of ATTR Val30Met familial amyloid polyneuropathy.
AB  - We report here two patients with amyloidogenic transthyretin (ATTR) Val30Met
      familial amyloid polyneuropathy (FAP) who developed numbness in both hands and
      were diagnosed as having bilateral carpal tunnel syndrome (CTS). In both patients
      systemic TTR amyloidosis consisting of polyneuropathy affecting both upper and
      lower limbs and/or autonomic dysfunction gradually appeared after surgery for
      CTS. Although CTS associated with TTR amyloidosis has been known as an initial
      symptom in some patients with ATTR non-Val30Met FAP and those with senile
      systemic amyloidosis, this is the first report of ATTR Val30Met FAP patients
      starting with upper limb neuropathy including CTS-like symptoms. It is also
      notable that both patients had no genealogical relationship with two Japanese
      endemic foci of this disease.

PMID- 20132089
TI  - Primary bladder amyloidosis--case report of a patient with delayed upper urinary
      tract obstruction 3 years after the diagnosis.
AB  - Primary bladder amyloidosis is a rare disease. There are approximately 100
      reported cases. The lesions can be confused with bladder neoplasm and are
      characterised histologically by the classical apple green birefringence under
      polarised light. In this article, we report a 51-year-old lady with known history
      of primary bladder amyloidosis presenting with gross hydronephrosis 3 years after
      the first diagnosis. Laparoscopic ileal replacement of bilateral ureters was
      performed. There was no recurrent ureteric obstruction 2 years after surgery.
      This case demonstrates the progressive nature of primary amyloidosis of bladder.
      The diagnosis of primary bladder amyloidosis warrants long-term surveillance of
      upper urinary tract.

PMID- 20132090
TI  - When urine is no longer beneficial: renal artery embolisation in severe nephrotic
      syndrome secondary to amyloidosis.
AB  - Renal artery embolisation (RAE) is an interventional radiology procedure which is
      used to embolise small branches of renal artery. It is mainly used for urologic
      purposes, i.e., vascular malformations, angiomyolipomas and renal tumours not
      amenable to surgical resection. Bilateral RAE can be performed via using absolute
      ethanol, polyvinyl alcohol or microparticles. After RAE, patients may experience
      post-embolisation syndrome which is usually self-limited. Use of this procedure
      for refractory nephrotic syndrome has been rarely defined in the literature to
      date. Here, we describe a patient who had nephrotic syndrome due to secondary
      systemic amyloidosis. The patient presented with severe proteinuria (33 g per
      day), hypoalbuminaemia and anasarca oedema. We applied bilateral RAE with
      microparticles. We did not observe any complications associated with the
      procedure. Protein excretion, laboratory values and clinical signs returned to
      normal.

PMID- 20132091
TI  - In vitro and in vivo investigation of glucose-mediated brain-targeting liposomes.
AB  - New glycosyl derivative of cholesterol was synthesized as a material for
      preparing novel liposome to overcome the ineffective delivery of normal drug
      formulations to brain by targeting the (glucose transporters) GLUTs on the BBB.
      Coumarin-6 was used as fluorescent probe. The results have shown that the
      cytotoxicity for the brain capillary endothelial cells (BCECs) of the glucose
      mediated brain targeting liposome containing coumarin-6 was less than that of
      conventional liposome. The BBB model in vitro was established by coculturing of
      BCECs and astrocytes (ACs) of rat to test the transendothelial ability crossing
      the BBB. The transendothelial ability was confirmed strengthen alone with the
      amount of the new glycosyl derivative of cholesterol used in liposome. After i.v.
      administration of LIP, control liposome (CLP), and GLP-4, the AUC(0-t) of
      coumarin-6 for GLP-4 was 2.85 times higher than that of LIP, and 3.33 times
      higher than that of CLP. The C(max) of CLP-4 was 1.43 times higher than that of
      LIP, and 3.10 times higher than that of CLP. Both pharmacokinetics and
      distribution in mice were also investigated to show that this novel brain
      targeting drug delivery system was promising.

PMID- 20132092
TI  - Rapid assessment of avoidable blindness and cataract surgical services in
      kilimanjaro region, Tanzania.
AB  - PURPOSE: To estimate the prevalence and causes of avoidable blindness and visual
      impairment in persons 50 years of age and older, and to assess the impact of
      cataract surgical services. METHODS: In this cross-sectional population-based
      survey, 72 clusters of 50 people 50 years and older were selected by probability
      proportionate to size sampling. Households within clusters were selected through
      compact segment sampling. Participants underwent an ophthalmic examination in
      their homes, including measurement of visual acuity (VA) with a tumbling-E chart
      and diagnosis of the principal cause of visual impairment. Patients who had been
      operated on were questioned about details of their cataract surgery. RESULTS:
      Three thousand six hundred eligible subjects were selected, of whom 3,436 (95.5%)
      were examined. The prevalence of bilateral blindness (presenting VA < 3/60) was
      2.4% (95% confidence interval [CI], 1.9%-2.9%); prevalence of severe visual
      impairment was 0.99% (95% CI, 0.98%-0.99%); and prevalence of visual impairment
      (VA of < 6/18 and > or = 6/60) was 5.4% (95% CI, 4.6%-6.2%) in the sample.
      Unoperated cataract accounted for 52.4% of blindness and 70.6% of severe visual
      impairment. Cataract surgical coverage among people at 3/60 was 68.9%. Overall,
      58.6% and 69.6% of the 191 eyes that had undergone cataract surgery had VA
      greater than or equal to 6/18 with available correction and best correction
      respectively. CONCLUSIONS: The prevalence of blindness in this population in
      Kilimanjaro Region was low, reflecting high cataract surgical coverage from an
      outreach program. Even with high cataract surgical coverage, cataract remains the
      leading cause of vision loss and an emphasis on quality is needed.

PMID- 20132093
TI  - Understanding delay in accessing specialist emergency eye care in a developing
      country: eye trauma in Tanzania.
AB  - PURPOSE: To determine the extent and reasons for delay in accessing specialist
      eye care following a significant eye injury. METHODS: Mixed methods study
      involving 93 consecutive admissions to Kilimanjaro Christian Medical Center,
      Tanzania (KCMC). Semi-structured interviews were conducted and supplemented by a
      review of medical notes. A statistical analysis of delay and predictor variables
      was conducted. Framework analysis of interviews was conducted. RESULTS: Ninety of
      93 patients took part. Significant visual loss was determined in 95.5% of
      affected eyes on arrival. The mean delay for treatment was 6.8 days. Of
      participants, 61.1% visited some health facility within 24 hours, and 82.2%
      within 48 hours. Injury on a weekend, using topical drops and visiting other
      health facilities before KCMC were independently associated with delay greater
      than 24 hours and greater than 48 hours, female gender with was associated with
      delay greater than 24 hours. Patient journeys involved key milestones and
      processes. Journeys were frequently "circular," involving delays caused by
      repeated visits to health units unable to treat the injury, often on a health
      worker's advice. Systems problems included unclear referral systems and opening
      times, frequent staff absence and unqualified staff deputizing. Individual health
      workers had an important influence on delay but their performance appeared
      variable. They influenced patient journeys positively when they made an accurate
      diagnosis, referred directly to KCMC, discussed practicalities and communicated
      the seriousness of the injury, the need for urgent treatment and the adverse
      consequences of delay. CONCLUSIONS: There is significant delay in accessing
      appropriate specialist care following eye injury in Tanzania, much of which
      occurs after first visiting a health facility. We present a new model of delay
      that may help guide interventions to reduce this delay.

PMID- 20132094
TI  - Distinctive features of "chronotherapeutic" and "pulsatile" drug delivery systems
      negating the practice of their interchangeable terminology.
AB  - The term pulsatile drug delivery has often been used as a synonym to
      chronotherapeutic drug delivery. This needs to be given a thought as both the
      drug delivery systems are entirely addressing different needs of the patients as
      well as the intentions of the formulators being different. Chronotherapeutic
      systems are based completely on circadian needs and response of the body and the
      need of the drug to be in its maximum concentrations at a particular time of the
      day, the fact being supported by endless list of ailments which elicit the
      related symptoms at a particular time of the day. Considering the formulation
      approach, one does not find major differences among site-specific
      chronotherapeutic systems and the basic and more conventional intestinal or colon
      targeted systems due to the mechanism and the site of landing of drug of both
      being almost similar even though the intention of the formulator being different.
      An ideal pulsatile system is the one delivering drug in different pulses with
      multiple troughs in release profile. The article explores the major differences
      in between the two systems and highlights the need of using appropriate
      terminology for these individual and distinct systems catering different needs.

PMID- 20132095
TI  - Oxygen transfer rate control in the production of human-like collagen by
      recombinant Escherichia coli.
AB  - The effects of different methods for elevating the OTR (oxygen transfer rate)
      during foreign gene expression and the cell growth of recombinant Escherichia
      coli BL21 were investigated. Two strategies were introduced to control DO
      (dissolved oxygen) levels in the fermentation broth: (i) increasing fermentor
      pressure and (ii) supplying oxygen-enriched air. These two methods were compared
      with the glucose feedback model, which acted as the control. By adopting a fed
      batch method of cultivation, the cell yield coefficient (YX/S), accumulation of
      acetic acid and volumetric product yield (Yp) were measured or estimated.
      Adoption of these two methods led to an improvement in the OTR. The cell density
      and volumetric product yield in the cultivation controlled by increasing the
      fermentor pressure reached 77 g x l(-1) (dry cell weight) and 14 g x l(-1)
      respectively, which were much higher than those obtained with the strategy of
      supplying oxygen-enriched air (48 and 6 g x l(-1) respectively) and in the
      control (46 and 7 g x l(-1) respectively). The results indicate that increasing
      fermentor pressure is an effective way to enhance the OTR and recombinant protein
      (human-like collagen) productivity.

PMID- 20132096
TI  - Administration of a low dose of sildenafil for 1 week decreases intrahepatic
      resistance in rats with biliary cirrhosis: the role of NO bioavailability.
AB  - Increasing NO bioavailability improves hepatic endothelial dysfunction, which
      ameliorates intrahepatic resistance and portal hypertension. Acute administration
      of sildenafil increases hepatic production of NO with a reduction in hepatic
      sinusoid resistance in cirrhotic patients and enhances the vasorelaxation
      response to NO in cirrhotic rat livers. However, the mechanisms were still
      unclear. Therefore, our present study aims to evaluate the effects and mechanisms
      of administration of sildenafil for 1 week on the hepatic microcirculation of
      cirrhotic rats. Cirrhosis was induced by bile duct ligation with sham-operated
      rats serving as normal controls. Intrahepatic resistance was evaluated by in situ
      liver perfusion. Expression of phospho-eNOS (endothelial NO synthase), iNOS
      (inducible NO synthase), phospho-Akt, PDE-5 (phosphodiesterase-5) and sGC
      (soluble guanylate cyclase) were determined by Western blot analysis.
      Biosynthesis of BH4 (tetrahydrobiopterin) and GTPCH-I (GTP cyclohydrolase I)
      activity were examined by HPLC. Intravital microscopy was used to observe the
      direct change in hepatic microcirculation. In cirrhotic rat livers, sildenafil
      treatment increased hepatic sinusoid volumetric flow, NO bioavailability, BH4,
      GTPCH-I activity, and the protein expression of phospho-Akt, phospho-eNOS and
      sGC. These events were associated with reduced protein expression of PDE-5,
      portal perfusion pressure and portal vein pressure. In contrast, sham rats did
      not produce any significant change in these measurements. In conclusion,
      sildenafil treatment improves endothelial dysfunction by augmenting NO
      bioavailability in the hepatic microcirculation.

PMID- 20132097
TI  - The role of RANTES as a crucial downstream cytokine in calcineurin-dependent VSMC
      apoptosis stimulated by INFgamma and CD40L.
AB  - Many studies have suggested that VSMC (vascular smooth muscle cell) apoptosis
      plays a key role in destabilization and rupture of atherosclerotic plaques.
      Therefore protection for VSMCs from apoptosis is a promising approach to
      stabilize 'vulnerable' lesions. However, the mechanisms as to why VSMCs in the
      fibrous cap often appear as profilerated in early stages, but turn apoptotic in
      advanced stages, are still unknown. In the present study, using RNAi (RNA
      interference) technology and a CaN (calcineurin) antagonist, the correlation
      between CaN and RANTES (regulated upon activation, normal T-cell expressed and
      secreted) in cultured rat apoptotic VSMCs stimulated by IFNgamma (interferon
      gamma; 20 ng/ml) and CD40L (CD40 ligand; 100 ng/ml) was investigated. RANTES
      released from VSMCs in each group was measured by ELISA and its mRNA in VSMCs was
      determined by RT (reverse transcription)-PCR. The total activity and expression
      of CaN in VSMCs were detected by the zymochemistry method and Western blot
      analysis respectively. From the results of the present study it can be
      hypothesized that an elevated CaN concentration in endochylema, by the CD40-CD40L
      signal pathway, induces VSMC apoptosis accomplished by the overexpression of
      RANTES. Therefore RANTES is a potential target for treating vulnerable
      atherosclerotic plaques owing to its crucial downstream regulating role in CaN
      dependent VSMC apoptosis.

PMID- 20132099
TI  - Does physical inactivity cause chronic obstructive pulmonary disease?
AB  - COPD (chronic obstructive pulmonary disease) is the most common pulmonary disease
      and is the only common cause of death in which mortality is presently rising. It
      is caused by the inhalation of smoke, which leads to oxidative stress and
      inflammation both in the lungs and systemically. Reduced physical activity is a
      well-recognized consequence of the condition, but we argue here that inactivity
      is itself an early cause of lung function decline and symptoms. This hypothesis
      is supported by data from population studies that link activity levels to decline
      in spirometric indices, both in smokers and non-smokers. In addition, smokers
      with low physical activity levels are more likely to be diagnosed subsequently
      with COPD. Physical exercise reduces oxidative stress, has an anti-inflammatory
      effect and reduces the frequency of upper respiratory tract infections, providing
      a number of mechanisms by which it could attenuate the harmful effects of
      smoking. There is sufficient evidence to justify population trials of lifestyle
      interventions aimed at improving physical activity levels and reducing lung
      function decline in people diagnosed with early COPD through spirometry
      screening.

PMID- 20132098
TI  - Cellular and molecular biology of Neisseria meningitidis colonization and
      invasive disease.
AB  - The human species is the only natural host of Neisseria meningitidis, an
      important cause of bacterial meningitis globally, and, despite its association
      with devastating diseases, N. meningitidis is a commensal organism found
      frequently in the respiratory tract of healthy individuals. To date, antibiotic
      resistance is relatively uncommon in N. meningitidis isolates but, due to the
      rapid onset of disease in susceptible hosts, the mortality rate remains approx.
      10%. Additionally, patients who survive meningococcal disease often endure
      numerous debilitating sequelae. N. meningitidis strains are classified primarily
      into serogroups based on the type of polysaccharide capsule expressed. In total,
      13 serogroups have been described; however, the majority of disease is caused by
      strains belonging to one of only five serogroups. Although vaccines have been
      developed against some of these, a universal meningococcal vaccine remains a
      challenge due to successful immune evasion strategies of the organism, including
      mimicry of host structures as well as frequent antigenic variation. N.
      meningitidis express a range of virulence factors including capsular
      polysaccharide, lipopolysaccharide and a number of surface-expressed adhesive
      proteins. Variation of these surface structures is necessary for meningococci to
      evade killing by host defence mechanisms. Nonetheless, adhesion to host cells and
      tissues needs to be maintained to enable colonization and ensure bacterial
      survival in the niche. The aims of the present review are to provide a brief
      outline of meningococcal carriage, disease and burden to society. With this
      background, we discuss several bacterial strategies that may enable its survival
      in the human respiratory tract during colonization and in the blood during
      infection. We also examine several known meningococcal adhesion mechanisms and
      conclude with a section on the potential processes that may operate in vivo as
      meningococci progress from the respiratory niche through the blood to reach the
      central nervous system.

PMID- 20132100
TI  - Changes in VEGF expression and DNA synthesis in hepatocytes from hepatectomized
      and tumour-bearing mice.
AB  - Transplanted tumours could modify the intensity and temporal distribution of the
      cellular proliferation in normal cell populations, and partial hepatectomy alters
      the serum concentrations of substances involved in cellular proliferation,
      leading to the compensatory liver hyperplasia. The following experiments were
      designed in order to study the SI (S-phase index) and VEGF (vascular endothelial
      growth factor) expression in regenerating liver (after partial hepatectomy) of
      adult male mice bearing a hepatocellular carcinoma, throughout one complete
      circadian cycle. We used adult male C3H/S-strain mice. After an appropriate
      period of synchronization, the C3H/S-histocompatible ES2a hepatocellular
      carcinoma was grafted into the subcutaneous tissue of each animal's flank. To
      determine the index of SI and VEGF expression of hepatocytes, we used
      immunohistochemistry. The animals were divided into two experimental groups:
      Group I, control, hepatectomized animals; Group II, hepatectomized tumour-bearing
      animals. The statistical analysis of SI and VEGF expression was performed using
      Anova and Tukey as a postcomparison test. The results show that in the second
      group, the curve of SI changes the time points for maximum and minimum activity,
      and the peak of VEGF expression appears before the first group. In conclusion, in
      the hepatectomized mice, the increases of hepatic proliferation, measured by the
      SI index, may produce a rise in VEGF expression with the object of generating a
      vascular network for hepatic regeneration. Lastly, as we have mentioned, in
      hepatectomized and tumour-bearing mice, the peak of VEGF expression appears
      before the one of DNA synthesis.

PMID- 20132102
TI  - Treatment costs of prostate cancer in the first year after diagnosis: a short
      term cost of illness study for France, Germany, Italy, Spain and the UK.
AB  - OBJECTIVE: To calculate the total cost per patient of prostate cancer treatment
      and the economic cost burden by stage, in the first year after diagnosis, for
      five European countries. METHODS: Data from the Information Management Systems,
      Inc. database, survival data, expert opinion, published data and unit costs from
      various published official sources were used to calculate total costs per patient
      by stage for each country, from a payer's perspective. Diagnostic costs, first
      surgery, radio-, chemo- and hormonal therapy costs were included. Costs were
      aggregated for incident cases. RESULTS: The mean direct costs per patient for
      initial treatment were euro3698 in Germany, euro3256 in Spain, euro3682 in the
      UK, euro5226 in Italy and euro5851 in France. The total costs for all diagnosed
      patients in the first year from diagnosis were (million euro) 116.7 (UK), 244
      (Germany), 385 (France), 202 (Italy) and 114.6 (Spain). CONCLUSIONS: The direct
      initial healthcare cost burden of the most common non-skin-related male cancer,
      prostate cancer, in France, Germany, Italy, Spain and the UK is considerable.
      Given the high and increasing prevalence of prostate cancer due to ageing
      populations in Europe, and the significant cost burden of the disease, national
      health policy makers should be aware of prostate cancer as a priority disease
      area.

PMID- 20132103
TI  - Comparison of fesoterodine and tolterodine extended release for the treatment of
      overactive bladder: a head-to-head placebo-controlled trial.
AB  - OBJECTIVE: To compare the efficacy and tolerability of fesoterodine 8 mg with
      tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial
      of patients with an overactive bladder (OAB). PATIENTS AND METHODS: In this 12
      week double-blind, double-dummy, placebo-controlled, randomized clinical trial,
      eligible patients reported OAB symptoms for > or = 3 months and recorded > or = 8
      voids and > or = 1 urgency urinary incontinence (UUI) episode per 24 h in 3-day
      bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to
      fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or
      placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints
      were changes from baseline to week 12 in UUI episodes (primary endpoint), total
      and nocturnal voids, urgency episodes, severe urgency episodes, and frequency
      urgency sum per 24 h; mean voided volume per void (MVV); and the OAB
      questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and
      Urgency Perception Scale (UPS). Safety and tolerability were assessed and
      summarized over the 12-week study period. RESULTS: Fesoterodine (636 patients)
      significantly improved UUI episodes at week 12 (primary endpoint) compared with
      tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001).
      Fesoterodine also produced significantly greater improvements than tolterodine ER
      in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints
      compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327).
      Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001),
      except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the
      proportion of patients reporting no UUI episodes at endpoint among those with one
      or more UUI episodes at baseline) were significantly higher with fesoterodine
      (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001).
      Improvements in PPBC, UPS and OAB-q scale and domain scores at week 12 were all
      significantly better with fesoterodine than placebo (all P < 0.001) and
      tolterodine ER (all P < 0.05) except for the OAB-q Sleep domain vs tolterodine ER
      (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine
      group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo,
      respectively. Discontinuations due to treatment-emergent adverse events were 6%,
      4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively.
      CONCLUSION: In patients with OAB, fesoterodine 8 mg showed superior efficacy over
      tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and
      in improving most patient-reported outcome measures. Both active treatments were
      well tolerated.

PMID- 20132104
TI  - Green shoots: but will the sap rise?

PMID- 20132105
TI  - Facilitating the medical management of benign prostatic hyperplasia in primary
      care.

PMID- 20132106
TI  - Screening for prostate cancer.

PMID- 20132107
TI  - Lingual mucosal grafts for anterior urethroplasty: a review.

PMID- 20132109
TI  - Glans resection and plastic repair.

PMID- 20132116
TI  - Drug interactions of clinical importance with methadone and buprenorphine.

PMID- 20132117
TI  - Drug interactions of clinical importance among the opioids, methadone and
      buprenorphine, and other frequently prescribed medications: a review.
AB  - Drug interactions are a leading cause of morbidity and mortality. Methadone and
      buprenorphine are frequently prescribed for the treatment of opioid addiction.
      Patients needing treatment with these medications often have co-occurring medical
      and mental illnesses that require medication treatment. The abuse of illicit
      substances is also common in opioid-addicted individuals. These clinical
      realities place patients being treated with methadone and buprenorphine at risk
      for potentially toxic drug interactions. A substantial literature has accumulated
      on drug interactions between either methadone or buprenorphine with other
      medications when ingested concomitantly by humans. This review summarizes current
      literature in this area.

PMID- 20132118
TI  - Interactions between buprenorphine and antiretrovirals: nucleos(t)ide reverse
      transcriptase inhibitors (NRTI) didanosine, lamivudine, and tenofovir.
AB  - To improve outcomes among injection drug users with HIV and/or chronic hepatitis
      B, it is important to identify drug interactions between antiretroviral and
      opiate therapies. We report the results of a study designed to examine the
      interaction between buprenorphine and the nucleos(t)ide reverse transcriptase
      inhibitors (NRTI) didanosine (ddI), lamivudine (3TC), and tenofovir (TDF). Opioid
      dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 27)
      participated in two 24-hour sessions to determine (1) pharmacokinetics of
      buprenorphine alone and (2) pharmacokinetics of both buprenorphine and either
      ddI, 3TC, or TDF. Among buprenorphine/naloxone-maintained study participants, no
      significant changes in buprenorphine pharmacokinetics were observed following
      ddI, 3TC, or TDF administration. Buprenorphine had no significant effect on NRTI
      concentrations. Concomitant use of buprenorphine with ddI, 3TC, or TDF results in
      neither a significant pharmacokinetic nor pharmacodynamic interaction.

PMID- 20132119
TI  - Lack of clinically significant drug interactions between nevirapine and
      buprenorphine.
AB  - This study was conducted to determine whether drug interactions of clinical
      importance occur between buprenorphine, an opioid partial agonist medication used
      in treatment of opioid dependence, and the nonnucleoside reverse transcriptase
      inhibitor (NNRTI) nevirapine. Opioid-dependent, buprenorphine/naloxone
      maintained, HIV-negative volunteers (n = 7) participated in 24-hour sessions to
      determine the pharmacokinetics of buprenorphine alone and of buprenorphine and
      nevirapine following administration of 200 mg nevirapine daily for 15 days.
      Opiate withdrawal symptoms, cognitive effects, and adverse events were determined
      prior to and following nevirapine administration. Modest decreases were observed
      for AUC for buprenorphine and its metabolites. There was a trend for more rapid
      clearance of both buprenorphine (p = .08) and buprenorphine-3-glucuronide (p =
      .08). While no single effect reached statistical significance, the joint
      probability that the consistent declines in all measures of exposure were due to
      chance was extremely low, indicating that nevirapine significantly reduces
      overall exposure to buprenorphine and buprenorphine metabolites. Clinically
      significant consequences of the interaction were not observed. Buprenorphine did
      not alter nevirapine pharmacokinetics. Dose adjustments of either buprenorphine
      or nevirapine are not likely to be necessary when these drugs are coadministered
      for the treatment of opiate dependence and HIV disease.

PMID- 20132120
TI  - Effect of cocaine use on buprenorphine pharmacokinetics in humans.
AB  - The effect of chronic cocaine use on buprenorphine pharmacokinetics was
      investigated to identify drug interactions and potential toxicities. In a
      retrospective analysis, pharmacokinetics were compared for 16 studies completed
      on subjects who were regular cocaine users and 74 studies on subjects who used
      cocaine only occasionally or not at all. All participants were stably maintained
      on buprenorphine/naloxone 16/4 mg daily. Participants who used cocaine regularly
      had lower buprenorphine exposure (AUC 34% lower; C(max) 27% lower and C(24) 37%
      lower; p <or= .001 for all comparisons). Regular cocaine users were younger (p =
      .0007), and used more heroin (p = .004) and cocaine (p < .0001). Regular cocaine
      use may result in lower buprenorphine plasma concentrations with potential for
      adverse clinical outcomes.

PMID- 20132121
TI  - Effect of cocaine use on methadone pharmacokinetics in humans.
AB  - Chronic cocaine use has been shown to significantly decrease buprenorphine
      concentrations in the blood with potential for adverse events and poor treatment
      response. In this study, we investigated whether a similar drug interaction
      occurred between cocaine and methadone. In a retrospective analysis, methadone
      pharmacokinetics were compared for those who were either regular cocaine users (N
      = 16) or with intermittent or no cocaine use (N = 23). Participants who used
      cocaine regularly showed a significant decrease in C(min) (p = .04) and a trend
      for decreased AUC (p = .09) and more rapid methadone clearance (p = .08). Regular
      cocaine use may adversely impact treatment outcomes for opioid dependence in
      those receiving methadone maintenance by decreasing methadone exposure.

PMID- 20132122
TI  - The association between cocaine use and treatment outcomes in patients receiving
      office-based buprenorphine/naloxone for the treatment of opioid dependence.
AB  - Cocaine use in patients receiving methadone is associated with worse treatment
      outcomes. The association between cocaine use and office-based
      buprenorphine/naloxone treatment outcomes is not known. We evaluated the
      association between baseline and in-treatment cocaine use, treatment retention,
      and urine toxicology results in 162 patients enrolled in a 24-week trial of
      primary care office-based buprenorphine/naloxone maintenance. Patients with
      baseline cocaine metabolite-negative urine toxicology tests compared with those
      with cocaine metabolite-positive tests had more mean weeks of treatment retention
      (18.3 vs. 15.8, p = .04), a greater percentage completed 24 weeks of treatment
      (50% vs. 33%, p = .04) and had a greater percentage of opioid-negative urines
      (47% vs. 34%, p = .02). Patients with in-treatment cocaine metabolite-negative
      urine toxicology tests compared with cocaine metabolite-positive patients had
      more mean weeks of treatment retention (19.0 vs. 16.5, p = .003), a greater
      percentage completed 24 weeks of treatment (60% vs. 30%, p < .001), and had a
      greater percentage of opioid-negative urines (51% vs. 35%, p = .001). We conclude
      that both baseline and in-treatment cocaine use is associated with worse
      treatment outcomes in patients receiving office-based buprenorphine/naloxone and
      may benefit from targeted interventions.

PMID- 20132123
TI  - Benzodiazepines, methadone and buprenorphine: interactions and clinical
      management.
AB  - Benzodiazepines (BZDs) are widely used by heroin users not in treatment, and by
      patients in methadone and buprenorphine (BPN) treatment. This review examines the
      epidemiology of BZD use by opioid users, and the range of harms that are
      associated with BZD use in this group, including the association of BZD use with
      opioid-related mortality. Preclinical and clinical data regarding pharmacokinetic
      and pharmacodynamic interactions between methadone, buprenorphine, and BZDs are
      reviewed. An overview of treatment approaches for managing BZD use in this
      population is presented, including strategies for minimizing abuse and addressing
      BZD dependence.

PMID- 20132124
TI  - Indicators of buprenorphine and methadone use and abuse: what do we know?
AB  - Abuse of prescription opioids is a growing problem. The number of methadone pain
      pills distributed now exceeds liquid methadone used in opioid treatment, and the
      increases in buprenorphine indicators provide evidence of the need to monitor and
      intervene to decrease the abuse of this drug. The need for additional and
      improved data to track trends is discussed, along with findings as to the
      characteristics of the users and combinations of drugs. Data on toxicities
      related to methadone or buprenorphine, particularly in combination with other
      prescribed drugs, are presented and clinical implications and considerations are
      offered. These findings underscore the need for physicians to be aware of
      potential toxicities and to educate their patients regarding these issues.

PMID- 20132125
TI  - Methadone and buprenorphine toxicity in children.
AB  - Recent years have seen very large increases in the prescribing of methadone and
      buprenorphine formulations for treatment of opioid addiction as well as the
      increasing utilization of methadone for the treatment of chronic pain. Coincident
      with the rise in the prescribing of these drugs has been a substantial increase
      in pediatric opioid toxicities and adverse events. This review will address the
      current state of methadone- and buprenorphine-related adverse events in children
      in the United States. We will also discuss treatment of opioid toxicity in
      pediatric populations and make recommendations aimed at reducing these
      occurrences.

PMID- 20132126
TI  - Drug interactions between antiretroviral medications and medications used in the
      treatment of drug addiction: research needs.
AB  - Today substance dependence is one of the major public health problems in the
      world with millions of people abusing legal and illegal drugs. In addition,
      almost one-third of the world's population suffers with one or more infections.
      Both drugs of abuse and infections are associated with serious medical and health
      consequences, some of which may be exacerbated by the occurrence of
      pharmacokinetic and/or pharmacodynamic interactions between medications used in
      the treatment of these conditions when they co-occur. This review briefly
      discusses issues surrounding clinical management related to drug interactions
      experienced by substance abusing patients. The emphasis of this paper is on the
      research needed to further study the extent, nature, and underlying
      molecular/genetic mechanism(s) of interactions between drugs of abuse,
      medications used in the treatment of drug addiction, and co-occurring infections.

PMID- 20132127
TI  - The effect of peripheral vascular disease on structure and function of resistance
      arteries isolated from human skeletal muscle.
AB  - Peripheral vascular disease (PVD) is associated with numerous pathophysiological
      adaptations of the microvasculature. Considering this, active and passive
      pressure-dependent and pressure-independent mechanisms of vascular control were
      studied in small resistance arteries isolated from patients with PVD. Using
      pressure myography and confocal microscopy, human skeletal muscle arteriolar
      structure and function were compared between paired arteries; one isolated from
      the healthy non-diseased proximal skeletal muscle vascular bed (PSM, internal
      control) and the other from the diseased ischaemic part of the leg [distal
      skeletal muscle (DSM)]. Structurally, arteries isolated from the diseased part of
      the leg displayed significant atrophy compared with the non-diseased arteries.
      Functionally, no differences were observed in the fundamental ability small
      resistance arteries to contract or relax. However, active pressure-dependent
      myogenic contraction was significantly reduced in DSM arteries compared with PSM
      arteries. DSM versus PSM; 3 +/- 1% versus 22 +/- 4% and 3.4% +/- 1.1% versus 25
      +/- 4% at 80 and 120 mmHg, respectively. Furthermore, structural remodelling in
      DSM arteries could also be correlated with significant changes in vascular wall
      mechanics. DSM arteries displayed significantly greater incremental
      dispensability, wall stress and wall strain compared with PSM arteries as a
      product of pressure-dependent distension. These alterations in pressure-dependent
      active myogenic tone and passive mechanical properties goes some way to explain
      uncontrolled orthostatic-dependent changes in leg fluid volume and oedema
      formation experienced by these patients.

PMID- 20132128
TI  - Late potentials and QT dispersion after high-dose chemotherapy in patients with
      non-Hodgkin lymphoma.
AB  - The most common cardiotoxic effects of high-dose cyclophosphamide (CY) are
      electrocardiographic changes and transient arrhythmias. Therefore, we
      prospectively assessed serial electrocardiogram (ECG) and signal-averaged
      electrocardiogram (SAECG) recordings in 30 adult patients with non-Hodgkin
      lymphoma (NHL) receiving high-dose CY as part of high-dose chemotherapy (HDT)
      regimen. All patients were treated with anthracyclines earlier. Heart-rate
      corrected QT interval and QT dispersion (QTc and QTc dispersion) were measured
      from ECG. QRS duration and late potentials (LPs) were analysed from SAECG. Both
      ECG and SAECG were recorded 1 day (d) prior to HDT (d-7) at baseline, and 1 day
      (d-2), 7 days (d+7), 12 days (+12) and 3 months (m+3) after HDT. Stem cells were
      infused on day 0 (d0). Cardiac systolic and diastolic function were assessed on
      (d-7), (d+12) and (m+3) by radionuclide ventriculography. At baseline, four
      patients presented with LPs. Cardiac systolic function decreased significantly
      (53 +/- 2; 49 +/- 2%, P = 0.009 versus baseline), whilst no patient developed
      acute heart failure. QRS duration prolonged and RMS(40) reduced significantly
      versus baseline (104 +/- 3; 107 +/- 3 ms, P = 0.003; 41 +/- 4; 38 +/- 3 microV, P
      = 0.03), and six patients (21%) presented with LPs after CY treatment. Both QTc
      interval and QTc dispersion increased versus baseline (402 +/- 5; 423 +/- 5 ms,
      P<0.001; 32 +/- 2; 44 +/- 3 ms, P = 0.012), and six patients (20%) developed
      abnormal QT dispersion. In conclusion, high-dose CY causes subclinical and
      transient electrical instability reflected by occurrence of LPs as well as
      increased QTc interval and QT dispersion. Thus, longer follow-up is required to
      confirm the meaning of these adverse effects on cardiac function and quality of
      life.

PMID- 20132129
TI  - Decreased leg glucose uptake during exercise contributes to the hyperglycaemic
      effect of octreotide.
AB  - AIM: During prolonged infusion of somatostatin, there is an increase in arterial
      glucose concentration, and this increase persists even during prolonged exercise.
      The aim of the study was to measure glucose uptake in the leg muscles during
      infusion of the somatostatin analogue octreotide before and during leg exercise.
      MATERIAL AND METHODS: Eight healthy male subjects were investigated twice in the
      fasting state: during 3 h infusion of octreotide [30 ng (kg min)(-1)] or sodium
      chloride with exercise at 50% of maximal VO(2) in the last hour. Glucose uptake
      and oxygen uptake in the leg were measured using Fick's principle by blood
      sampling from an artery and a femoral vein. Blood flow in the leg was measured
      using the indicator (indocyanine green) dilution technique. RESULTS: After an
      initial decrease during rest, octreotide infusion resulted in a significant
      increase in arterial glucose concentrations compared to control conditions during
      exercise (mean +/- SEM: 7.6 +/- 0.6 versus 5.6 +/- 0.1 mmol l(-1), P<0.01).
      During rest, octreotide did not change the leg glucose uptake (59 +/- 10 versus
      55 +/- 11 micromol min(-1)). In contrast, leg glucose uptake was significantly
      lower during exercise compared to control conditions (208 +/- 79 versus 423 +/-
      87 micromol min(-1), P<0.05). During exercise, leg oxygen uptake was not
      different in the two experiments (20.4 +/- 1.3 versus 19.5 +/- 1.1 micromol min(
      1)). CONCLUSION: In conclusion, infusion of octreotide reduced leg glucose uptake
      during exercise, despite the same leg oxygen consumption and blood flow compared
      to control conditions. The hyperglycaemic effect of octreotide can partly be
      explained by the reduction in leg glucose uptake. Furthermore, the results
      suggest that a certain level of circulating insulin is necessary to obtain
      sufficient stimulation of glucose uptake in the exercising muscles.

PMID- 20132130
TI  - Spindle cell lesion of thyroid: a potential pitfall in FNAC diagnosis.

PMID- 20132131
TI  - Thyroid fine needle aspiration cytology processed by ThinPrep: an additional
      slide decreased the number of inadequate results.
AB  - BACKGROUND: Fine needle aspiration cytology is the most accurate tool for
      diagnosing thyroid nodules. Its accuracy is related to the rate of inadequate
      samples, which can be minimized with the adoption of on-site assessment of the
      adequacy of the material. The introduction of liquid-based cytology (LBC) in the
      thyroid does not allow checking on the adequacy of the cellularity. The
      possibility of making a second LBC slide for decreasing the number of non
      diagnostic cases is studied. METHODS: Out of 553 cases diagnosed in a single
      institution from January to March 2005, 166 consecutive cases with an LBC slide
      reviewed by the same pathologist were evaluated. The cases were classified in a
      five-tiered category system (Thy1 to 5 according to the British Thyroid
      Association guidelines) and all but two (with cystic degeneration) were processed
      by LBC and stained with Papanicolaou stain. The above-mentioned categories are
      defined as follows: Thy1 inadequate or haemorrhagic, Thy2 non-neoplastic lesion;
      Thy3 follicular lesion/suspected follicular neoplasm; Thy4 suspicious for
      malignancy; Thy5 diagnostic of malignancy. For each case the cytological
      diagnosis was made on the LBC slide and the adequacy of the cellularity for a
      conclusive diagnosis was assessed. RESULTS: Of the 166 cases, 39 were non
      diagnostic (Thy1-inadequate), ten presented features of cystic degeneration (Thy1
      haemorrhagic), 90 were benign (Thy2), 22 were diagnosed as a follicular lesion
      (Thy3), one as suspicious of malignancy (Thy4) and four as papillary carcinoma
      (Thy5). Thirty-nine cases had a second LBC for achieving a definitive diagnosis
      with eventual re-classification. Of these cases, 23 (61.5%) led to a conclusive
      diagnosis (18 Thy2, five Thy3) with a 18.5% decrease of the inadequacy rate.
      CONCLUSIONS: The making of an additional LBC slide helps in achieving a diagnosis
      in cases classified as non-diagnostic on the first standard slide (52.1% recovery
      rate). This procedure is particularly helpful for meeting the adequacy criteria
      in benign and indeterminate lesions and could also be used for refining the
      diagnosis of suspicious for a malignant thyroid neoplasm.

PMID- 20132132
TI  - Fine needle aspiration cytology and flow cytometry immunophenotyping of non
      Hodgkin lymphoma: can we do better?
AB  - OBJECTIVE: To evaluate the diagnostic efficiency of fine needle aspiration
      cytology/flow cytometry (FNAC/FC) in the diagnosis and classification of non
      Hodgkin lymphoma (NHL) in a series of 446 cases and to compare the results with
      those of previous experiences to evaluate whether there had been an improvement
      in FNAC/FC diagnostic accuracy. METHODS: FNAC/FC was used to analyse 446 cases of
      benign reactive hyperplasia (BRH), NHL and NHL relapse (rNHL) in 362 lymph nodes
      and 84 extranodal lesions. When a diagnosis of NHL was reached, a classification
      was attempted combining FC data and cytological features. Sensitivity,
      specificity and positive and negative predictive values (PPV and NPV) of FNAC/FC
      in the diagnosis and classification of NHL were calculated and compared with
      those available in the literature. RESULTS: FNAC/FC provided a diagnosis of NHL
      and rNHL in 245 cases and of BRH in 188 cases. In nine cases, the diagnosis was
      'suggestive of NHL' (sNHL) and in four cases was inadequate. Histology and
      clinical follow-up confirmed 102 cases of NHL and detected one false positive. In
      18 cases of BRH diagnosed by FNAC/FC, histological examination revealed 14 BRH
      and four NHL (false negatives). All nine cases diagnosed as sNHL were confirmed
      by histology. Including sNHL cases as false negatives, statistical analysis
      showed 94.9% sensitivity, 99.4% specificity, 99.6% PPV and 93.4% NPV in the
      diagnosis of NHL. A specific subtype was diagnosed in 125 cases and confirmed in
      67 of 70 cases that had histological biopsies. Statistical analysis did not
      demonstrate significant improvements between the present series and previous
      studies either in diagnosis or in classification of NHL. CONCLUSIONS: FNAC/FC is
      a fundamental tool in the diagnosis and classification of NHL but the exiguity of
      diagnostic material and other technical and clinical limitations will probably
      continue to limit further improvement of the technique.

PMID- 20132133
TI  - The cannabinoid antagonist SR144528 enhances the acute effect of WIN 55,212-2 on
      gastrointestinal motility in the rat.
AB  - BACKGROUND: In the absence of pathology, cannabinoid-induced depression of
      gastrointestinal (GI) motility is thought to be mediated primarily by CB1
      receptors, whereas the role of CB2 receptors is still unclear. The aim of this
      work was to radiographically analyze the acute effect of the mixed cannabinoid
      agonist WIN 55,212-2 (WIN) on GI motor function in the rat, focusing on the
      involvement of CB1 and CB2 receptors. METHODS: Male Wistar rats received
      different doses of WIN and both psychoactivity (cannabinoid tetrad) and GI
      motility (radiographic analysis) were tested. The duration of WIN effect on GI
      motility was also radiographically analyzed. Finally, the involvement of the
      different cannabinoid receptors on WIN-induced alterations of GI motility was
      analyzed by the previous administration of selective CB1 (AM251) and CB2
      (SR144528 or AM630) antagonists. After administration of contrast medium,
      alterations in GI motility were quantitatively evaluated in serial radiographs by
      assigning a compounded value to each region of the GI tract. KEY RESULTS: Low,
      analgesic doses of WIN delayed intestinal transit, but high, psychoactive doses
      were required to delay gastric emptying. Acute WIN effects on GI motility were
      confined to the first few hours after administration. AM251 partially
      counteracted the effect of WIN on GI motility. Surprisingly, SR144528 (but not
      AM630) enhanced WIN-induced delayed gastric emptying. CONCLUSIONS & INFERENCES: X
      ray analyses confirm that cannabinoids inhibit GI motility via CB1 receptors; in
      addition, cannabinoids could influence motility through interaction with a
      SR144528-sensitive site. Further studies are needed to verify if such site of
      action is the CB2 receptor.

PMID- 20132134
TI  - Anticipatory postural adjustments in a bimanual load-lifting task in children
      with developmental coordination disorder.
AB  - AIM: Postural control is a fundamental component of action in which deficits have
      been shown to contribute to motor difficulties in children with developmental
      coordination disorder (DCD). The purpose of this study was to examine
      anticipatory postural adjustments (APAs) in children with DCD in a bimanual load
      lifting task. METHOD: Sixteen children with reported motor problems (two females,
      14 males; mean age 9 y; SD 2 y) and 16 typically developing, age-matched children
      (six females, 10 males; mean age 9 y; SD 2 y) took part in the study. The task
      required the children to maintain a stable elbow angle, despite imposed or
      voluntary unloading of the forearm. APAs were assessed using electromyography and
      kinematics analysis. RESULTS: Although children with DCD could compensate for the
      consequences of unloading, the results demonstrated that APAs were less efficient
      in children with DCD than in typically developing children. A positive and
      significant coefficient of regression between the flexor inhibition latency and
      the postural stabilization was only found in typically developing children.
      INTERPRETATION: The impaired fine-tuning of the muscle contribution and the poor
      stabilization performances demonstrate poor predictive modelling in DCD.

PMID- 20132135
TI  - Stability of motor problems in young children with or at risk of autism spectrum
      disorders, ADHD, and or developmental coordination disorder.
AB  - AIM: The aim of this study was to investigate the stability of motor problems in
      a clinically referred sample of children with, or at risk of, autism spectrum
      disorders (ASDs), attention-deficit-hyperactivity disorder (ADHD), and/or
      developmental coordination disorder (DCD). METHOD: Participants were 49 children
      (39 males, 10 females; mean age 5y 6 mo, SD 10 mo) with various developmental
      problems, a Movement Assessment Battery for Children (M-ABC) score on or below
      the 15th centile, and an IQ of 70 or more. Sixteen children were at risk of
      developing ADHD, 15 children had a diagnosis of, or were at risk of developing
      ASD, and 18 children had neither diagnosis. Children were reassessed 2 to 3 years
      later. RESULTS: At follow-up (mean age 7y 11 mo; SD 1y), the mean M-ABC score was
      significantly increased, and in 22 children was no longer below the 15th centile.
      A general linear model to compare the difference in M-ABC scores in the three
      groups of children demonstrated a significant difference between groups
      (p=0.013), with the age at the initial assessment as a significant covariate
      (p=0.052). The group of children with or at risk of ASD showed less improvement
      in motor performance. INTERPRETATION: Motor problems among preschool age children
      are not always stable, but appear to be so in most children with ASDs.

PMID- 20132136
TI  - Effectiveness of functional progressive resistance exercise strength training on
      muscle strength and mobility in children with cerebral palsy: a randomized
      controlled trial.
AB  - AIM: To evaluate the effectiveness of functional progressive resistance exercise
      (PRE) strength training on muscle strength and mobility in children with cerebral
      palsy (CP). METHOD: Fifty-one children with spastic uni- and bilateral CP; (29
      males, 22 females; mean age 10 y 5 mo, SD 1 y 10 mo, range 6 y 0 mo-13 y 10 mo;
      Gross Motor Function Classification System levels I-III) were randomized to the
      intervention group (n=26) or the control group (n=25, receiving usual care). The
      intervention group trained for 12 weeks, three times a week, on a five-exercise
      circuit, which included a leg-press and functional exercises. The training load
      progressively increased based on the child's maximum level of strength,
      determined by the eight-repetition maximum. Muscle strength (measured with hand
      held dynamometry and a six-repetition maximum leg-press test), mobility (measured
      with the Gross Motor Function Measure, two functional tests, and a mobility
      questionnaire), and spasticity (measured by the appearance of a catch) were
      evaluated before, during, directly after, and 6 weeks after the end of training
      by two blinded research assistants. RESULTS: Directly after training, there was a
      statistically significant effect (p<0.05) on muscle strength (knee extensors +12%
      [0.56 N/kg; 95% confidence interval {CI} 0.13-0.99]; hip abductors +11% [0.27
      N/kg; 95% CI 0.00-0.54]; total +8% [1.30 N/kg; 95% CI 0.56-2.54]; six-repetition
      maximum +14% [14%; 95% CI 1.99-26.35]), but not on mobility or spasticity. A
      detraining effect was seen after 6 weeks. INTERPRETATION: Twelve weeks of
      functional PRE strength training increases muscle strength up to 14%. This
      strength gain did not lead to improved mobility.

PMID- 20132137
TI  - Characterization of spasticity in cerebral palsy: dependence of catch angle on
      velocity.
AB  - AIM: To evaluate spasticity under controlled velocities and torques in children
      with cerebral palsy (CP) using a manual spasticity evaluator. METHOD: The study
      involved 10 children with spastic CP (six males, four females; mean age 10 y 1
      mo, SD 2 y 9 mo, range 7-16 y; one with quadriplegia, six with right hemiplegia,
      three with left hemiplegia; Gross Motor Function Classification System levels I
      [n=2], II [n=3], III [n=2], IV [n=2], and V [n=1]; Manual Ability Classification
      System levels II [n=5], III [n=4], and V [n=1]) and 10 typically developing
      participants (four males, six females; mean age 10 y 3 mo, SD 2 y 7 mo, range 7
      15 y). Spasticity and catch angle were evaluated using joint position, resistance
      torque, and torque rate at velocities of 90 degrees, 180 degrees, and 270 degrees
      per second, controlled using real-time audio-visual feedback. Biomechanically,
      elbow range of motion (ROM), stiffness, and energy loss were determined during
      slow movement (30 degrees/s) and under controlled terminal torque. RESULTS:
      Compared with typically developing children, children with CP showed higher
      reflex-mediated torque (p<0.001) and the torque increased more rapidly with
      increasing velocity (p<0.001). Catch angle was dependent on velocity and occurred
      later with increasing velocity (p=0.005). Children with CP showed smaller ROM
      (p<0.05), greater stiffness (p<0.001), and more energy loss (p=0.003).
      INTERPRETATION: Spasticity with velocity dependence may also be position
      dependent. The delayed catch angle at higher velocities indicates that the
      greater resistance felt by the examiner at higher velocities was also due to
      position change, because the joint was moved further to a stiffer position at
      higher velocities.

PMID- 20132138
TI  - An internet-based physical activity intervention for adolescents with cerebral
      palsy: a randomized controlled trial.
AB  - AIM: To determine the effectiveness of an 8-week internet-based, lifestyle
      physical-activity intervention for adolescents with cerebral palsy (CP). METHOD:
      A randomized controlled trial using concealed allocation with blinded assessments
      at baseline, 10, and 20 weeks. Forty-one adolescents with CP participated (26
      males, 15 females; mean age 13y 7mo, SD 1y 8mo, range 11-17y; Gross Motor
      Function Classification System levels: I, n=21; II, n=17; III, n=3; unilateral
      distribution n=16, bilateral n=25). Primary outcome was physical activity (NL
      1000 accelerometers and self-report [Multimedia Activity Recall for Children and
      Adolescents: MARCA]). Secondary outcomes were exercise knowledge (a purpose
      designed scale), attitudes, intention and self-efficacy (Lifestyle Education for
      Activity Program II scales), self-reported sedentary behaviour (MARCA), and
      functional capacity (6-min walk test). RESULTS: At 10 weeks the intervention
      group showed no increased physical activity compared with the comparison group
      (weekly steps: change of +2420 vs -12189 steps p=0.06; weekly moderate-to
      vigorous physical activity: change of +70 vs +8min, p=0.06; weekly distance
      walked: change of +3 vs -9.1km, p=0.05) and exercise knowledge (12% vs 1%
      improvement, p=0.08). There were no statistically significant differences for
      these outcomes at 20 weeks, or in self-reported physical activity at 10 or 20
      weeks. INTERPRETATION: There was a positive short-term pattern for improvement in
      physical activity and knowledge. Internet-based programs may offer an alternative
      for participants unable to attend regular face-to-face physical activity
      programs.

PMID- 20132139
TI  - Mechanical properties of the plantarflexor musculotendinous unit during passive
      dorsiflexion in children with cerebral palsy compared with typically developing
      children.
AB  - AIM: To examine the passive length-tension relations in the myotendinous
      components of the plantarflexor muscles of children with and without cerebral
      palsy (CP) under conditions excluding reflex muscle contraction. METHOD: A cross
      sectional, non-interventional study was conducted in a hospital outpatient
      clinic. Passive torque-angle characteristics of the ankle were quantified from
      full plantarflexion to full available dorsiflexion in 26 independently ambulant
      children with CP (11 females, 15 males; mean age: 6 y 11 mo, range 4 y 7 mo-9 y 7
      mo) and 26 age-matched typically developing children (18 females, 8 males; mean
      age 7 y 2 mo, range 4 y 1 mo-10 y 4 mo). In the children with CP, the affected
      (hemiplegia; n=21) or more affected (diplegia; n=5) leg was tested; in typically
      developing children, the leg tested was randomly selected. Gross Motor Function
      Classification System levels were I (n=15) and II (n=11). Care was taken to
      eliminate active or reflex muscle contribution to the movement, confirmed by the
      absence of electromyographic activity. RESULTS: There were small but significant
      differences between the two groups for maximum ankle dorsiflexion (p=0.003), but
      large and significant differences in the torques required to produce the same
      displacement (p<0.001). Further, the hysteresis of the average loading cycle in
      the children with CP was over three times that of the typically developing
      children (p<0.001). INTERPRETATION: We believe that the plantarflexor muscles of
      children with CP are stiffer and intrinsically more resistant to stretch, even
      though they retain near normal excursion. This increased stiffness is a non
      neurally-mediated feature demonstrated by these children. The extent to which it
      influences function and predisposes the children to development of soft tissue
      contracture is unknown.

PMID- 20132140
TI  - Investigation of childhood central nervous system vasculitis: magnetic resonance
      angiography versus catheter cerebral angiography.
AB  - AIM: We compared the clinical utility of magnetic resonance angiography (MRA) to
      catheter cerebral angiography (CA) in the investigation of children with
      suspected central nervous system (CNS) vasculitis. METHOD: Single-centre
      retrospective review of children with a suspected diagnosis of CNS vasculitis
      studied with both MRA and CA. MRA and CA-detected abnormalities (location,
      multiplicity, and morphology) were compared; sensitivity and specificity were
      calculated on a per lesion and per patient basis for MRA, with CA as the
      reference standard. RESULTS: Findings in fourteen patients (median age at
      presentation of 5 y 10 mo [range 1 y 5 mo-14 y 5 mo]; eight males, six females)
      relating to sixteen paired studies of MRA and CA were reviewed. CA-detected
      lesions were commonly bilateral (13/16 studies, p<0.05), and likely to be
      proximally distributed (15/16 studies, p<0.05).The sensitivity and specificity of
      MRA for CA lesion detection was 63% (95% confidence interval [CI] 48-78) and 89%
      (95% CI 81-93), respectively with moderate agreement between the two modalities
      (kappa=0.51, 95% CI 0.37-0.66). The majority of the false negative observations
      involved the posterior circulation (9/14). The overall sensitivity for MRA
      diagnosis of vasculitis per patient was 94% (95% CI 67-99). INTERPRETATION: MRA
      failed to identify all lesions detected on CA, particularly those in the
      posterior circulation. MRA is a reasonable initial modality in the investigation
      of suspected CNS vasculitis but in cases of abnormal parenchymal MRI and normal
      MRA, CA should be considered.

PMID- 20132141
TI  - Diffusion-weighted imaging of cerebral white matter and the cerebellum following
      preterm birth.
AB  - AIM: The aim of this study was to determine if apparent diffusion coefficients
      (ADCs) generated with diffusion-weighted imaging of cerebral white matter and the
      cerebellum are affected by white matter damage. METHOD: Seventy-two preterm
      infants (32 males, 40 females; mean gestational age at birth 30.3 wks, SD 3.0
      wks; mean birthweight 1458g, SD 534g) underwent magnetic resonance imaging of the
      brain around term-equivalent age and were categorized into three groups: normal,
      overt abnormality, and diffuse excessive high signal intensity (DEHSI). ADC
      values were calculated from cerebral white matter, cerebellar hemispheres, and
      cerebellar midline, and were compared between groups. Regression analysis
      identified clinical parameters correlated with ADC values. RESULTS: Imaging was
      normal in 27 infants, and revealed overt abnormalities in 14 and DEHSI in 31. ADC
      values did not differ between groups. ADC values from cerebral white matter were
      negatively correlated with the number of episodes of postnatal sepsis (p=0.002).
      ADC values from cerebellar hemispheres (p=0.007) and cerebellar midline (p=0.036)
      correlated with gestational age at birth. INTERPRETATION: ADC values from white
      matter are not altered in preterm infants with DEHSI but are negatively
      correlated with the number of episodes of postnatal sepsis. ADC values in the
      cerebellum are not altered by white matter damage, but are affected by preterm
      birth itself.

PMID- 20132142
TI  - The relationship between unimanual capacity and bimanual performance in children
      with congenital hemiplegia.
AB  - AIM: This study explores the relationship between unimanual capacity and bimanual
      performance for children with congenital hemiplegia aged 5 to 16 years. It also
      examines the relationship between impairments and unimanual capacity and bimanual
      performance. METHOD: Participants in this cross-sectional study attended a
      screening assessment before participating in a large, randomized trial. They
      comprised 70 children with congenital hemiplegia (39 males, 31 females; mean age
      10 y 6 mo, SD 3 y); 18 were classified in the Manual Ability Classification
      System level I, 51 in level II, and one in level III. Eighteen were in Gross
      Motor Function Classification System, level I and 52 in level II. Sixty-five
      participants had spasticity and five had dystonia and spasticity. Fifteen
      typically developing children (7 males, 8 females; mean age 8 y 8 mo, SD 2 y 7
      mo), matched to study participants for age and sex, were recruited as a
      comparison group for measures of sensation, grip strength, and movement
      efficiency. Outcome measures for unimanual capacity were the Melbourne Assessment
      of Unilateral Upper Limb Function (MUUL), and the Jebsen-Taylor Hand Function
      Test (JTHFT). The Assisting Hand Assessment (AHA) evaluated bimanual performance.
      Upper limb impairments were measured using assessments of stereognosis, moving
      two-point discrimination, spasticity, and grip strength. RESULTS: There was a
      strong relationship between unimanual capacity (MUUL) and bimanual performance
      (AHA; r=0.83). Linear regression indicated MUUL and stereognosis accounted for
      75% of the variance in AHA logit scores. Sensory measures were moderately
      correlated with unimanual capacity and bimanual performance. Age, sex, and grip
      strength did not significantly influence bimanual performance. There was no
      difference between children with right- and left-sided hemiplegia for motor
      performance. INTERPRETATION: Findings of our study confirm a strong relationship
      between unimanual capacity and bimanual performance in a cohort of children with
      congenital hemiplegia. However, the directionality of the relationship is unknown
      and therapists cannot assume improvements in unimanual capacity will lead to
      gains in bimanual performance.

PMID- 20132143
TI  - Rating scales for dystonia in cerebral palsy: reliability and validity.
AB  - AIM: This study investigated the reliability and validity of the Barry-Albright
      Dystonia Scale (BADS), the Burke-Fahn-Marsden Movement Scale (BFMMS), and the
      Unified Dystonia Rating Scale (UDRS) in patients with bilateral dystonic cerebral
      palsy (CP). METHOD: Three raters independently scored videotapes of 10 patients
      (five males, five females; mean age 13 y 3 mo, SD 5 y 2 mo, range 5-22 y). One
      patient each was classified at levels I-IV in the Gross Motor Function
      Classification System and six patients were classified at level V. Reliability
      was measured by (1) intraclass correlation coefficient (ICC) for interrater
      reliability, (2) standard error of measurement (SEM) and smallest detectable
      difference (SDD), and (3) Cronbach's alpha for internal consistency. Validity was
      assessed by Pearson's correlations among the three scales used and by content
      analysis. RESULTS: Moderate to good interrater reliability was found for total
      scores of the three scales (ICC: BADS=0.87; BFMMS=0.86; UDRS=0.79). However, many
      subitems showed low reliability, in particular for the UDRS. SEM and SDD were
      respectively 6.36% and 17.72% for the BADS, 9.88% and 27.39% for the BFMMS, and
      8.89% and 24.63% for the UDRS. High internal consistency was found. Pearson's
      correlations were high. Content validity showed insufficient accordance with the
      new CP definition and classification. INTERPRETATION: Our results support the
      internal consistency and concurrent validity of the scales; however, taking into
      consideration the limitations in reliability, including the large SDD values and
      the content validity, further research on methods of assessment of dystonia is
      warranted.

PMID- 20132144
TI  - White matter changes in extremely preterm infants, a population-based diffusion
      tensor imaging study.
AB  - AIM: To investigate cerebral white matter (WM) abnormalities (J Pediatr 2003;
      143: 171) and diffuse and excessive high signal intensities (DEHSI), (J Pediatr
      1999; 135: 351) in a cohort of extremely preterm infants born in Stockholm during
      a 3-year period, using magnetic resonance imaging (MRI) and diffusion tensor
      imaging (DTI). METHODS: MRI at term-equivalent age was performed in 109 infants
      and DTI data were acquired in 54 infants. Survival rate in the entire cohort was
      67%. Sixteen term-born healthy control infants were scanned for comparison.
      RESULTS: No or mild WM abnormalities were seen in 86% of infants and 14% had
      moderate or severe WM abnormalities. DEHSI were seen in infants with all grades
      of white matter abnormalities and were present in 56% of infants. In the WM at
      the level of centrum semiovale, infants with any WM abnormalities or DEHSI had
      lower Fractional Anisotropy and higher Apparent Diffusion Coefficient compared
      with control infants. No significant differences in diffusion were seen in
      infants without DEHSI compared with the controls in this region. Compared with
      controls, the preterm infants had significantly altered diffusion in the corpus
      callosum. CONCLUSION: Only 14% of the extremely preterm infants had moderate or
      severe WM abnormalities on MRI. However, the incidence of DEHSI was high. In the
      DEHSI regions, changes in diffusion parameters were detected, indicating altered
      WM organization.

PMID- 20132145
TI  - Self-assessed and objective blood phenylalanine levels in patients with early
      treated phenylketonuria.

PMID- 20132146
TI  - Cardiac basal metabolism: energetic cost of calcium withdrawal in the adult rat
      heart.
AB  - AIM: Cardiac basal metabolism upon extracellular calcium removal and its
      relationship with intracellular sodium and calcium homeostasis was evaluated.
      METHODS: A mechano-calorimetric technique was used that allowed the simultaneous
      and continuous measurement of both heat rate and resting pressure in arterially
      perfused quiescent adult rat hearts. Using pharmacological tools, the possible
      underlying mechanisms related to sodium and calcium movements were investigated.
      RESULTS: Resting heat rate (expressed in mW g(-1)(dry wt)) increased upon calcium
      withdrawal (+4.4 +/- 0.2). This response was: (1) unaffected by the presence of
      tetrodotoxin (+4.3 +/- 0.6), (2) fully blocked by both, the decrease in
      extracellular sodium concentration and the increase in extracellular magnesium
      concentration, (3) partially blocked by the presence of either nifedipine (+2.8
      +/- 0.4), KB-R7943 (KBR; +2.5 +/- 0.2), clonazepam (CLO; +3.1 +/- 0.3) or EGTA
      (+1.9 +/- 0.3). The steady heat rate under Ca(2+)-free conditions was partially
      reduced by the addition of Ru360 (-1.1 +/- 0.2) but not CLO in the presence of
      EGTA, KBR or Ru360. CONCLUSION: Energy expenditure for resting state maintenance
      upon calcium withdrawal depends on the intracellular rise in both sodium and
      calcium. Our data are consistent with a mitochondrial Ca(2+) cycling, not
      detectable under normal calcium diastolic levels. The experimental condition here
      analysed, partially simulates findings reported under certain pathological
      situations including heart failure in which mildly increased levels of both
      diastolic sodium and calcium have also been found. Therefore, under such
      pathological conditions, hearts should distract chemical energy to fuel processes
      associated with sodium and calcium handling, making more expensive the
      maintenance of their functions.

PMID- 20132147
TI  - Adenosine A(1) receptors and vascular reactivity.
AB  - AIM: Blood pressure is higher in A(1) receptor knock-out (A(1)R-/-) mice than in
      wild type litter mates (A(1)R+/+) and we have examined if this could be related
      to altered vascular functions. METHODS: Contraction of aortic rings and
      mesenteric arteries were examined. To examine if the adenosine A(1) receptor
      mediated contraction of aortic muscle was functionally important we examined
      pulse pressure (PP) and augmentation index (AIX) using a sensor that allows
      measurements of rapid pressure transients. RESULTS: Contraction of aortic rings
      to phenylephrine and relaxation to acetylcholine were similar between genotypes.
      The non-selective adenosine receptor agonist N-ethyl carboxamido adenosine (NECA)
      enhanced the contractile response, and this was eliminated in aortas from A(1)R-/
      mice. However, in mesenteric arteries no contractile response was seen and
      adenosine-mediated relaxation was identical between studied genotypes. A(2B)
      adenosine receptors, rather than A(2A) receptors, may be mainly responsible for
      the vasorelaxation induced by adenosine analogues in the examined mouse vessels.
      PP was higher in A(1)R-/- mice, but variability was unaltered. AIX was not
      different between genotypes, but the NECA-induced fall was larger in A(1)R-/-
      mice. CONCLUSIONS: The role of adenosine A(1) receptors in regulating vessel tone
      differs between blood vessels. Furthermore, contractile effects on isolated
      vessels cannot explain the blood pressure in A(1) knock-out mice. The A(1)
      receptor modulation of blood pressure is therefore mainly related to
      extravascular factors.

PMID- 20132149
TI  - Repolarization of the cardiac action potential. Does an increase in
      repolarization capacity constitute a new anti-arrhythmic principle?
AB  - The cardiac action potential can be divided into five distinct phases designated
      phases 0-4. The exact shape of the action potential comes about primarily as an
      orchestrated function of ion channels. The present review will give an overview
      of ion channels involved in generating the cardiac action potential with special
      emphasis on potassium channels involved in phase 3 repolarization. In humans,
      these channels are primarily K(v)11.1 (hERG1), K(v)7.1 (KCNQ1) and K(ir)2.1
      (KCNJ2) being the responsible alpha-subunits for conducting I(Kr), I(Ks) and
      I(K1). An account will be given about molecular components, biophysical
      properties, regulation, interaction with other proteins and involvement in
      diseases. Both loss and gain of function of these currents are associated with
      different arrhythmogenic diseases. The second part of this review will therefore
      elucidate arrhythmias and subsequently focus on newly developed chemical entities
      having the ability to increase the activity of I(Kr), I(Ks) and I(K1). An
      evaluation will be given addressing the possibility that this novel class of
      compounds have the ability to constitute a new anti-arrhythmic principle.
      Experimental evidence from in vitro, ex vivo and in vivo settings will be
      included. Furthermore, conceptual differences between the short QT syndrome and
      I(Kr) activation will be accounted for.

PMID- 20132150
TI  - Lactose intolerance in patients with chronic functional diarrhoea: the role of
      small intestinal bacterial overgrowth.
AB  - BACKGROUND: Many studies report a high prevalence of lactose intolerance in
      patients with functional, gastrointestinal disease. AIM: To evaluate the role of
      small intestinal bacterial overgrowth (SIBO) in condition of lactose intolerance
      and the mechanism by which SIBO may impact lactose tolerance in affected
      patients. METHODS: Consecutive out-patients with chronic functional diarrhoea
      (CFD) and healthy controls underwent a validated 20 g lactose hydrogen breath
      test (HBT). Patients completed also a 10 g lactulose HBT with concurrent
      assessment of small bowel transit by scintigraphy. RESULTS: Lactose malabsorption
      was present in 27/31 (87%) patients with CFD and 29/32 (91%) healthy controls (P
      = 0.708). From the patient group 14/27 (52%) had lactose intolerance and 13/27
      (48%) experienced no symptoms (lactose malabsorption controls). Only 5 (17%)
      healthy controls reported symptoms (P < 0.01). The oro-caecal transit time was
      similar between patient groups with or without symptoms (P = 0.969). SIBO was
      present in 11 (41%) subjects and was more prevalent in lactose intolerance than
      in lactose malabsorption [9/14 (64%) vs. 2/13 (15%), P = 0.018]. Symptom severity
      was similar in lactose intolerance patients with and without SIBO (P = 0.344).
      CONCLUSIONS: Small intestinal bacterial overgrowth increases the likelihood of
      lactose intolerance in patients with CFD as a direct result of lactose
      fermentation in the small intestine, independent of oro-caecal transit time and
      visceral sensitivity.

PMID- 20132151
TI  - Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia
      induced post-infectious irritable bowel syndrome and functional dyspepsia.
AB  - BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) and functional
      dyspepsia (FD) have been described after both Campylobacter jejuni
      gastroenteritis and Giardia infection. After C. jejuni, there is increased rectal
      serotonin (5-HT)-containing EC cells and postprandial plasma 5-HT, while a pilot
      study suggested increased plasma cholecystokinin (CCK) after Giardia infection.
      AIM: To determine changes in plasma and duodenal mucosal 5-HT and CCK in Giardia
      induced PI-IBS. METHODS: A total of 32 patients previously infected with Giardia
      and 19 who had recovered fully (controls) completed symptom questionnaires.
      Endoscopic duodenal biopsies were obtained from all subjects and
      immunohistochemically stained for CCK, 5-HT and CgA containing entero-endocrine
      cells and mast cells. 5-HT content was also assessed. Twenty-one of 32 patients
      and 19 controls consumed a high-carbohydrate meal, while fasting and postprandial
      plasma CCK and 5-HIAA were measured. RESULTS: Post-infectious irritable bowel
      syndrome patients had increased numbers of CCK cells (P = 0.02), but lower
      numbers of EC cells (P = 0.009). Plasma CCK did not differ significantly between
      the groups, but correlated significantly with postprandial dyspepsia scores (r =
      0.5, P = 0.05). PI-IBS patients had significantly lower plasma 5-HIAA, before and
      after meal (P = 0.05) as well as more dyspepsia (P < 0.0001) compared with
      recovered subjects. CONCLUSIONS: Post-infectious bowel dysfunction following
      Giardia infection is associated with increased duodenal mucosal CCK. Postprandial
      dyspeptic symptoms correlate better with CCK than measures of 5-HT metabolism.

PMID- 20132152
TI  - Clinical trial: irsogladine maleate, a mucosal protective drug, accelerates
      gastric ulcer healing after treatment for eradication of Helicobacter pylori
      infection--the results of a multicentre, double-blind, randomized clinical trial
      (IMPACT study).
AB  - BACKGROUND: Helicobacter pylori eradication therapy alone is not sufficient to
      heal all gastric ulcers. AIM: To verify the efficacy of treatment with
      irsogladine maleate between the termination and assessment of treatment for
      eradicating H. pylori in a double-blind study. METHODS: Three hundred and twenty
      two patients with a single H. pylori-positive gastric ulcer were given
      eradication treatment, then assigned randomly to a treatment group [given 4
      mg/day irsogladine maleate (n = 150)] or a control group [given a placebo (n =
      161)]. The gastric ulcer healing rates were compared after 7 weeks of treatment.
      RESULTS: The healing rate was significantly higher in the irsogladine maleate
      group (83.0%) than in the placebo group (72.2%; chi2 test, P = 0.0276). In the
      subgroup analysis of cases of eradication failure, the gastric ulcer healing rate
      was significantly higher in the irsogladine maleate group (57.9%) than in the
      placebo group (26.1%; chi2 test, P = 0.0366). CONCLUSIONS: Irsogladine maleate
      was effective for treating gastric ulcer after H. pylori eradication. The high
      healing rates observed in patients with or without successful eradication
      demonstrate the usefulness of irsogladine maleate treatment regardless of the
      outcome of eradication.

PMID- 20132153
TI  - Effects of a single dose of rabeprazole 20 mg and pantoprazole 40 mg on 24-h
      intragastric acidity and oesophageal acid exposure: a randomized study in gastro
      oesophageal reflux disease patients with a history of nocturnal heartburn.
AB  - BACKGROUND: Nocturnal heartburn is common in patients with gastro-oesophageal
      reflux disease (GERD). AIM: To compare the effects of single doses of rabeprazole
      20 mg and pantoprazole 40 mg on 24-h intragastric acidity and oesophageal acid
      exposure (OAE). METHODS: A total of 52 subjects with GERD and a >or=6-month
      history of heartburn were randomized into a blinded, 2 x 2 crossover trial.
      Subjects' intragastric pH was monitored in two 48-h study periods with 6- to 13
      day washout between periods. Patients received placebo on day 1, a single dose of
      rabeprazole 20 mg or pantoprazole 40 mg on day 2, and standardized meals
      throughout. RESULTS: The mean percentage time with intragastric pH >4 was
      significantly greater with rabeprazole vs. pantoprazole for the 24-h postdose
      interval (44.0% vs. 32.8%; P < 0.001). Significant differences were observed in
      the daytime (51.0% vs. 42.2%; P < 0.001) and nighttime (32.0% vs. 16.9%; P <
      0.001). Rabeprazole was also significantly superior in other intragastric pH
      parameters. There was no statistical difference for OAE between treatments.
      CONCLUSIONS: In GERD patients with nocturnal heartburn, rabeprazole 20 mg was
      significantly more effective than pantoprazole 40 mg in percentage time with
      intragastric pH >4 during the nighttime, daytime, and 24-h periods. Differences
      between treatments in OAE were not demonstrated. This trial is registered with
      http://clinicaltrials.gov, number NCT00237367.

PMID- 20132154
TI  - Clinical trial: maintenance intermittent therapy with rabeprazole 20 mg in
      patients with symptomatic gastro-oesophageal reflux disease - a double-blind,
      placebo-controlled, randomized study.
AB  - BACKGROUND: Optimal long-term management of symptomatic gastro-oesophageal reflux
      disease (sGERD) patients has not been established. AIM: To determine the clinical
      value of maintenance intermittent treatment with rabeprazole 20 mg vs. placebo in
      patients with sGERD. METHODS: This multicentre, US study enrolled patients with
      sGERD (>or=3-month history of GERD symptoms and >or=4 days/week of heartburn
      during a 2-week placebo run-in) without oesophageal erosions. Patients with
      complete heartburn control after 4 weeks of open-label rabeprazole 20 mg daily
      treatment were randomized to 6-month, double-blind, maintenance intermittent
      treatment (7- to 14-day courses when heartburn recurred) with rabeprazole 20 mg
      or placebo. RESULTS: The primary efficacy end point, mean percentage of heartburn
      free days, was significantly greater with rabeprazole vs. placebo: 82.58% and
      62.17% (ITT; P < 0.0001) [per protocol 86.74% rabeprazole vs. 74.93% placebo (P <
      0.0254)]. Compared with placebo group, the rabeprazole group also experienced a
      significantly higher percentage of heartburn-free daytime (84.06% vs. 63.39%; P <
      0.0001) and nighttime (95.41% vs. 90.25%; P = 0.0021) periods, had significantly
      fewer discontinuations because of insufficient heartburn control (6.3% vs. 36.3%;
      P < 0.0001) and took fewer antacid tablets daily (0.58 vs. 1.16; P = 0.0021).
      CONCLUSION: Intermittent use of rabeprazole may be an effective maintenance
      treatment strategy for patients with sGERD and warrants further investigation.
      This trial was registered with http://clinicaltrials.gov under the number
      NCT00165841.

PMID- 20132155
TI  - Stratum corneum lipids, skin barrier function and filaggrin mutations in patients
      with atopic eczema.
AB  - BACKGROUND: Prior to the discovery of filaggrin (FLG) mutations, evidence for an
      impaired skin barrier in atopic dermatitis (AD) has been documented, and changes
      in ceramide profile, altered skin pH and increased trans-epidermal water loss
      (TEWL) in patients with AD have been reported. Until now, no studies have
      analysed stratum corneum (SC) lipids combined with skin barrier parameters in
      subjects of known FLG genotype. METHODS: A cohort of 49 German individuals
      genotyped for the most common FLG mutations (R501X, 2282del4) had SC samples
      taken for lipid analysis by high-performance thin layer chromatography. In
      addition, TEWL, erythema, skin hydration and pH were measured. In 27 of the 49
      individuals, a 24-h irritation patch test with sodium lauryl sulphate was
      performed. For the analysis, both the AD group and the control group were
      stratified by FLG mutation status (FLGmut/FLGwt). RESULTS: In the FLGmut AD
      group, significantly lower levels of ceramide 4 and significantly higher levels
      of ceramide 7 were observed when compared to both healthy control groups.
      However, ceramide 7 levels also significantly differed between FLGwt AD and FLGwt
      controls, as did ceramide 1 levels. No significant differences were observed for
      ceramide 2, 3, 5 and 6. FLGmut individuals had significantly higher skin pH
      values than individuals not carrying FLG mutations. Patients with AD with FLG
      mutations had significantly higher erythema compared to patients with AD without
      FLG mutations. CONCLUSION: Our results confirm previous observations of altered
      ceramide levels in AD, which however appear to show no clear relationship with
      FLG mutations.

PMID- 20132156
TI  - Staphylococcus aureus enterotoxin B augments granulocyte migration and survival
      via airway epithelial cell activation.
AB  - BACKGROUND: Staphylococcus aureus enterotoxin B (SEB) has recently been
      postulated to be involved in the pathology of granulocyte-dominated disease.
      Studying the immunologic interaction between SEB and airway epithelial cells in
      immortalized cell lines or long-term epithelial cell cultures has obvious
      disadvantages. METHODS: We used a novel technique of freshly isolated and
      purified human nasal epithelial cells (HNEC) from healthy, nonallergic
      individuals, which were incubated for 24 h without/with SEB at different
      concentrations. Chemokine production was evaluated in the supernatant using
      Cytometric Bead Array. The chemotactic activity of the supernatant was studied in
      vitro using a Boyden chamber. Survival was evaluated with flow cytometry, using
      propidium iodide to identify dead cells. RESULTS: Staphylococcus aureus
      enterotoxin B showed a dose-dependent induction of interferon-inducible protein
      10, monokine induced by interferon-gamma, regulated upon activation normal T cell
      expressed and secreted, monocyte chemoattractant protein 1 (MCP-1) and
      granulocyte colony stimulating factor production by epithelial cells in vitro.
      The supernatant of epithelial cells had chemotactic activity for granulocytes in
      vitro, which was enhanced in the supernatant of SEB-stimulated epithelial cells.
      Reduced number of propidium iodide positive granulocytes was found in the
      conditions where supernatant of SEB-stimulated epithelial cells was applied.
      CONCLUSION: Staphylococcus aureus enterotoxin B exerts a direct pro-inflammatory
      effect on HNEC, with induction of chemokine and growth factor release, resulting
      in the migration and prolonged survival of granulocytes in vitro.

PMID- 20132157
TI  - Risk factors of new-onset asthma in adults: a population-based international
      cohort study.
AB  - BACKGROUND: The occurrence of new-onset asthma during adulthood is common, but
      there is insufficient understanding of its determinants including the role of
      atopy. OBJECTIVE: To assess the risk factors for the development of new-onset
      asthma in middle-aged adults and to compare them according to atopy. METHODS: A
      longitudinal analysis of 9175 young adults who participated in two surveys of the
      European Community Respiratory Health Survey (ECRHS) conducted 9 years apart.
      FINDINGS: We observed 179 cases of new-onset asthma among 4588 participants who
      were free of asthma and reported at the beginning of the follow-up that they had
      never had asthma (4.5 per 1000 person-years). In a logistic regression, the
      following risk factors were found to increase the risk of new-onset asthma:
      female gender (OR: 1.97; 95% confidence interval (CI): 1.38, 2.81), bronchial
      hyperresponsiveness (3.25; 2.19, 4.83), atopy (1.55; 1.08, 2.21), FEV(1) < 100 %
      predicted (1.87; 1.34, 2.62), nasal allergy (1.98;1.39,2.84) and maternal asthma
      (1.91; 1.13; 3.21). Obesity, respiratory infections in early life and high-risk
      occupations increased the risk of new-onset asthma although we had limited power
      to confirm their role. Among the atopics, total IgE and sensitization to cat were
      independently related to the risk of new-onset asthma. The proportion of new
      onset asthma attributable to atopy varied from 12% to 21%. CONCLUSION: Adults
      reporting that they had never had asthma were at a substantial risk of new-onset
      asthma as a result of multiple independent risk factors including lung function.
      Atopy explains a small proportion of new-onset adult asthma.

PMID- 20132158
TI  - The allergen Bet v 1 in fractions of ambient air deviates from birch pollen
      counts.
AB  - BACKGROUND: Proof is lacking that pollen count is representative for allergen
      exposure, also because allergens were found in nonpollen-bearing fractions of
      ambient air. OBJECTIVE: We monitored simultaneously birch pollen and the major
      birch pollen allergen Bet v 1 in different size fractions of ambient air from
      2004 till 2007 in Munich, Germany. METHODS: Air was sampled with a ChemVol high
      volume cascade impactor equipped with stages for particulate matter (PM)>10
      microm, 10 microm>PM>2.5 microm, and 2.5 microm>PM>0.12 microm. Allergen was
      determined with a Bet v 1-specific ELISA. Pollen count was assessed with a
      Burkard pollen trap. We also measured the development of allergen in pollen
      during ripening. RESULTS: About 93 +/- 3% of Bet v 1 was found in the PM > 10
      microm fraction, the fraction containing birch pollen. We did not measure any Bet
      v 1 in 2.5 microm > PM > 0.12 microm. Either in Munich no allergen was in this
      fraction or the allergen was absorbed to diesel soot particles that also deposit
      in this fraction. Pollen released 115% more Bet v 1 in 2007 than in 2004. Also
      within 1 year, the release of allergen from the same amount of pollen varied more
      than 10-fold between different days. This difference was explained by a rapidly
      increasing expression of Bet v 1 in pollen in the week just before pollination.
      Depending on the day the pollen is released during ripening, its potency varies.
      CONCLUSION: In general, pollen count and allergen in ambient air follow the same
      temporal trends. However, because a 10-fold difference can exist in allergen
      potency of birch pollen, symptoms might be difficult to correlate with pollen
      counts, but perhaps better with allergen exposure.

PMID- 20132159
TI  - Impact of allergic rhinitis on asthma in children: effects on bronchial
      hyperreactivity.

PMID- 20132160
TI  - Aspirin tolerance in patients with NSAID-hypersensitivity.

PMID- 20132161
TI  - IgE-mediated anaphylaxis to pristinamycin - report of a case.

PMID- 20132162
TI  - Is physician-diagnosed allergic rhinitis a risk factor for the development of
      asthma?
AB  - BACKGROUND: There is strong evidence that there is a relationship between
      allergic rhinitis (AR) and asthma, but it is unclear whether there is a causal
      relation between AR and asthma. The aim of this study was to assess prospectively
      whether AR is a risk factor for the diagnosis of asthma in a large primary care
      population. METHODS: We performed a historic cohort study of life-time morbidity
      that had been recorded prospectively since 1967 in four general practices. Two
      groups of subjects were selected: (i) patients with diagnosis of AR, (ii) a
      control group matched using propensity scores. We assessed the risk of physician
      diagnosed asthma in patients with physician-diagnosed AR compared to subjects
      without a diagnosis of AR (controls). RESULTS: The study population consisted of
      6491 subjects (n = 2081 patients with AR). Average study follow-up was 8.4 years.
      In patients with AR, the frequency of newly diagnosed asthma was 7.6% (n = 158)
      compared to 1.6% (n = 70) in controls (P < 0.001). After adjusting the effect of
      AR on asthma diagnosis for registration time, age, gender, eczema and
      socioeconomic status, having AR was a statistically significant risk factor for
      asthma (hazard ratio: 4.86, P < 0.001, 95% confidence interval: 3.50-6.73,
      controls as reference). CONCLUSION: A diagnosis of AR was an independent risk
      factor for asthma in our primary care study population. Having physician
      diagnosed AR increased the risk almost fivefold for a future asthma diagnosis.

PMID- 20132163
TI  - Temporal changes in UK birth order and the prevalence of atopy.
AB  - BACKGROUND: Many studies have reported an inverse association between birth order
      and the risk of respiratory allergic disease. In recent decades, the prevalence
      of atopy has increased alongside reductions in fertility rates. AIMS OF THE
      STUDY: To quantitate how much of the increased prevalence of atopy, measured by
      skin prick test or specific IgE, can be attributed to temporal changes in family
      size in the United Kingdom. METHODS: Through a systematic literature review
      (MEDLINE, 1965-2009), five studies of UK populations were identified and their
      data were included in the calculation of a summary odds ratio for the risk of
      atopy for each birth order. Information on changes in UK family sizes between
      1960 and 2001 was obtained from Eurostat. On this basis, expected increases in
      the prevalence of atopy were calculated by weighting the proportion in each birth
      order category for 1960 and 2001 by the summary odds ratio for that category and
      then calculating the relative risk of atopy in 2001 compared with 1960. RESULTS:
      The pooled summary odds ratios for atopy were 0.90, 0.69 and 0.69 for those born
      second, third and fourth (or higher), respectively. The expected relative
      increase in the prevalence of atopy resulting from a change in family size
      between 1960 and 2001 was 3%. CONCLUSIONS: Despite the strong associations
      between birth order and atopy, reductions in family size in the last 40 years
      account for little of the increase in atopy.

PMID- 20132164
TI  - Antiphospholipid antibodies limit trophoblast migration by reducing IL-6
      production and STAT3 activity.
AB  - PROBLEM: Women with antiphospholipid antibodies (aPL) are at risk of recurrent
      miscarriage and pre-eclampsia. aPL target the placenta by binding to beta(2)
      glycoprotein I (beta(2) GPI) expressed by the trophoblast. The objective of this
      study was to evaluate if and how aPL affect first trimester trophoblast
      migration. METHOD OF STUDY: First trimester trophoblast cells were treated with
      anti-beta(2) GPI monoclonal antibodies. Migration was determined using a two
      chamber assay. Interleukin (IL)-6 production was evaluated by RT-PCR and enzyme
      linked immunosorbent assay, and signal transducer and activator of transcription
      3 (STAT3) activation was assessed by western blot. RESULTS: Trophoblast cells
      constitutively secreted IL-6 in a time-dependent manner and this directly
      correlated with STAT3 phosphorylation. In the presence of anti-beta(2) GPI Abs,
      trophoblast IL-6 mRNA levels and secretion was downregulated in a Toll-like
      receptor 4/MyD88-independent manner and this correlated with a reduction in
      phosphorylated STAT3 levels. In addition, the anti-beta(2) GPI Abs reduced the
      migratory potential of trophoblast. Heparin was able to reverse aPL-dependent
      inhibition of trophoblast IL-6 secretion and migration. CONCLUSION: This study
      demonstrates that aPL limit trophoblast cell migration by downregulating
      trophoblast IL-6 secretion and STAT3 activity. As heparin was unable to prevent
      these effects, our findings may explain why women with antiphospholipid syndrome,
      treated with heparin, remain at risk of developing obstetrical syndromes,
      associated with impaired deep placentation, such as pre-eclampsia.

PMID- 20132165
TI  - Serum anti-endometrial antibodies in infertile women - potential risk factor for
      implantation failure.
AB  - PROBLEM: Female infertility patients with diverse etiologies show increased
      production of autoantibodies. METHOD OF STUDY: Immunoblot analysis of sera from
      patients with endometriosis and tubal factor infertility (TFI) and mass
      spectrometry identification of candidate antigens. RESULTS: The immunoblot
      results demonstrated the presence of IgA and IgG anti-endometrial antibodies
      (AEA) to various antigens at molecular weights ranging from 10 to 200 kDa.
      Differences were detected in certain AEA reactions between the patients' groups
      and particular AEA were associated with in vitro fertilization (IVF) implantation
      failure. IgA AEA to a 47-kDa protein were more prevalent in TFI patients and were
      associated with unsuccessful IVF treatment. This antigen was subsequently
      identified as alpha-enolase. CONCLUSION: Determination of the presence and
      spectra of AEA in patients with endometriosis and TFI undergoing IVF may be a
      useful marker to predict their pregnancy outcome.

PMID- 20132166
TI  - Good ethics requires good science: why transplant programs should not disclose
      misattributed parentage.
AB  - In 1996, I argued that the recommendation by the Institute of Medicine (IOM) to
      inform women when tests reveal misattributed paternity and not to disclose this
      information to the women's partners was morally wrong. I argued in favor of
      disclosure to both parties. It is a position that I still hold. But claims of
      misattributed paternity are not 'incidental findings' as it was called in the old
      genetics literature, but a rather serious indictment of biological infidelity. In
      this paper I argue that the tests used by transplant programs for living donor
      recipient compatibility are inadequate to accurately determine misattributed
      paternity. Further I argue that it is not the responsibility of the transplant
      community to undertake such serious forensic evaluations. Genetic inconsistencies
      in ABO and HLA inheritance should be reported as variations. Families who want
      further clarification should be referred to a genetic professional.

PMID- 20132167
TI  - What the medical excuse teaches us about the potential living donor as patient.
AB  - Since the inception of living donor kidney transplantation, physicians have
      expressed concern about the voluntariness of the donors and their ability to
      recuse themselves. The literature from the late 1960s and early 1970s reveals the
      practice of offering a false medical excuse, although more recent comments seem
      to focus more on a 'general statement of lack of suitability' or 'a blameless
      explanation'. Simmerling et al. argue that the provision of a medical excuse
      rests on deception, which is wrong on deontological grounds (that physicians
      should hold to a principle of veracity) and on consequential grounds (deception
      threatens to damage trust and the doctor-patient relationship and deception may
      have adverse impact on the donor's relationship with his family). In this paper I
      examine and reject these objections. I argue that a false medical excuse is
      morally unjustifiable, but the medical excuse understood as a 'general statement
      of lack of suitability' is morally permissible because it promotes donor autonomy
      (the donor's right to decide whether or not to donate), and protects and
      preserves the donor's rights to privacy and confidentiality (by affirming the
      donor as an independent patient).

PMID- 20132168
TI  - Defining the canonical form of T-cell-mediated rejection in human kidney
      transplants.
AB  - Banff defines T-cell-mediated rejection (TCMR) using nonspecific lesions and
      arbitrary cutoffs, with no external gold standard. We reexamined features of TCMR
      using exclusively molecular definition independent of histopathology. The
      definition was derived from mouse kidney transplants with fully developed TCMR,
      and is based on high expression of transcripts reflecting IFNG effects and
      alternative macrophage activation. In 234 human kidney transplant biopsies for
      cause phenotyped by microarrays, we identified 26 biopsies meeting these
      criteria. After excluding three biopsies with unrelated diseases, all 23 biopsies
      had typical Banff lesions of TCMR (inflammation, tubulitis), with v lesions in
      10/23. Banff histopathology diagnosed 18 as TCMR, 1 as mixed and 4 as borderline.
      Despite marked changes in transcriptome indicating tissue injury and
      dedifferentiation, all kidneys with molecularly defined TCMR, even with v lesions
      or late rejection, demonstrated excellent recovery of function at 6 months with
      no graft loss (mean follow-up 2.5 years). Thus TCMR defined exclusively by
      molecules manifests TCMR-related lesions and function impairment, but good
      recovery and survival, even with late rejection or arteritis. This combination of
      pathologic, clinical and molecular features constitutes the typical or canonical
      T-cell-mediated rejection.

PMID- 20132169
TI  - Cyclosporine A protects against primary biliary cirrhosis recurrence after liver
      transplantation.
AB  - Primary biliary cirrhosis (PBC) reoccurs in a proportion of patients following
      liver transplantation (LT). The aims of our study were to evaluate the risk
      factors associated with PBC recurrence and determine whether recurrent disease
      constitutes a negative predictor for survival. One hundred and eight patients
      receiving LT for end-stage PBC were studied. Recurrent disease was diagnosed in
      28 patients (26%). Probability of recurrent PBC at 5 years was 13% and 29% at 10
      years with an overall incidence of 3.97 cases per 100 patient years. By
      univariate Cox analysis use of tacrolimus (HR 6.28, 95% CI, 2.44-16.11, p <
      0.001) and mycophenolate mofetil (HR 5.21, 95% CI, 1.89-14.33, p = 0.001) were
      associated with higher risk of recurrence; whereas use of cyclosporine A (CsA)
      and azathioprine were associated with reduced risk of recurrence (HR 0.13, 95% CI
      0.05-0.35, p < 0.001 and HR 0.27, 95% CI 0.11-0.64, p = 0.003, respectively). In
      the multivariate Cox analysis, only CsA was independently associated with
      protection against recurrence (HR 0.17, 95% CI 0.06-0.71, p = 0.02). Five-year
      probability of survival was 83% and 96%, in patients without and with recurrence
      (log-rank test, p = 0.3). Although PBC transplant recipients receiving CsA have a
      lower risk of disease recurrence, the development of recurrent PBC did not impact
      on long-term patient survival.

PMID- 20132170
TI  - Making sense of desensitization.
AB  - Several questions must be addressed to determine whether desensitization plus
      paired exchange is an appropriate strategy for renal transplantation.

PMID- 20132171
TI  - AMACR is not applicable as a diagnostic tool in hepatocellular carcinoma.
AB  - Alpha-methylacyl coenzyme A racemase (AMACR or P504S) is a mitochondrial and
      peroxisomal protein present in a variety of human cells. Demonstration of
      increased expression is used diagnostically in prostatic adenocarcinoma. AMACR is
      also produced by normal hepatocytes and it has been postulated that the
      demonstration of AMACR expression or its pattern of distribution is useful in the
      diagnosis of hepatocellular carcinoma (HCC) (Jiang et al., Hum Pathol 2003;34,
      Guzman et al., Appl Immunohistochem Mol Morphol 2006;14, Li et al., J Exp Clin
      Cancer Res 2008;27). The aim of the present study was to evaluate whether
      immunohistochemical staining for AMACR can be used in a routine histopathologic
      setting. Immunohistochemical staining for AMACR was performed on paraffin
      embedded tissue from livers resected for HCC during 1980-2006 at Rigshospitalet,
      Copenhagen, Denmark (n = 44). Tumor sections as well as surrounding non
      neoplastic tissues were studied. In both tumor and non-tumor tissues,
      intracellular localization and staining pattern were assessed and the staining
      intensity of AMACR was graded. The fraction of stained tumor cells was not
      significantly different from that of stained non-tumor cells in the same patients
      (p = 0.97). A significantly lower staining intensity was observed in clear cell
      areas (p = 0.005), but the AMACR expression did not correlate with the HCC type
      and could not distinguish neoplastic from non-neoplastic liver cells. AMACR is
      not applicable as a tool in the histopathologic diagnosis of HCC.

PMID- 20132172
TI  - Variable expression of tenascin-C, osteopontin and fibronectin in inflammatory
      myofibroblastic tumour of the lung.
AB  - The aim of this study was to analyse the expression of tenascin-C, osteopontin
      and fibronectin in inflammatory myofibroblastic tumour of the lung, which is a
      rare tumour of unknown aetiology. Nine patients with an inflammatory
      myofibroblastic tumour of lung were studied by immunohistochemistry for the
      presence of tenascin-C, osteopontin, fibronectin and alpha-smooth muscle actin,
      which is a common marker for myofibroblasts. The ultrastructure of myofibroblasts
      was confirmed by transmission electron microscopy. The expression of tenascin-C,
      osteopontin, fibronectin and alpha-smooth muscle actin was also studied by
      immunoelectron microscopy. All cases displayed all of the studied extracellular
      matrix proteins and also alpha-smooth muscle actin-positive spindle-shaped
      fibroblastic cells that were undoubtedly myofibroblasts. The immunoelectron
      microscopic studies demonstrated labelling for alpha-smooth muscle actin in
      intracellular filament bundles within myofibroblasts, for fibronectin in the
      extracellular filaments of the fibronexus and for tenascin-C extracellularly
      often adjacent to myofibroblasts. Labels for osteopontin were observed within
      myofibroblasts and plasma cells. These results demonstrate that tenascin-C,
      osteopontin and fibronectin were expressed in all three kinds of subtypes of
      inflammatory myofibroblastic tumours of the lung and further, variable amounts of
      myofibroblasts could be observed by light and transmission electron microscopy as
      well as by immunoelectron microscopic techniques.

PMID- 20132173
TI  - Effect of renal and non-renal ischemia/reperfusion on cell-mediated immunity in
      organs and plasma.
AB  - Acute renal failure (ARF) is a common morbidity factor among patients in the
      intensive care unit, reaching an incidence from 3% to 30% depending on the
      definition of ARF and the population. Although the majority of the patients with
      ARF are treated with continuous renal replacement therapy, the mortality rate
      still remains above 50%. The causes of death are primarily extra-renal and
      include infection, shock, septicemia, and respiratory failure. We wanted to
      evaluate the cell-mediated inflammatory response of renal ischemia-reperfusion
      (I/R) and non-renal I/R, in blood and in distant organs. In our study, 80 mice
      were divided into four groups. The following surgeries were performed on the
      groups compared: bilateral renal I/R by clamping, unilateral renal ischemia,
      anesthesia only, and unilateral hind leg I/R. Half of the animals were killed
      after 2 h and the other half after 24 h. To assess the inflammatory response, we
      measured myeloperoxidase (MPO) in the organs, and CD 11b and major
      histocompatibility complex (MHC) II-positive cells in the blood. Non-renal I/R
      elicited the most elevated levels of MPO in extra-renal tissue such as the lungs.
      There was a trend toward higher MPO levels in the kidney following renal I/R. All
      kinds of I/R induced an upregulation of the adhesion molecule CD 11b and a
      downregulation of MHC II. Renal and non-renal I/R induced neutrophil infiltration
      in distant organs. Renal I/R does not induce a larger cell-mediated inflammatory
      response in blood and organs than non-renal I/R.

PMID- 20132174
TI  - Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of
      human dendritic cells.
AB  - Development of hypoxic areas occurs during infectious and inflammatory processes
      and dendritic cells (DCs) are involved in both innate and adaptive immunity in
      diseased tissues. Our group previously reported that macrophages exposed to
      hypoxia were infected with the intracellular parasite Leishmania amazonensis, but
      showed reduced susceptibility to the parasite. This study shows that although
      hypoxia did not alter human DC viability, it significantly altered phenotypic and
      functional characteristics. The expression of CD1a, CD80, and CD86 was
      significantly reduced in DCs exposed to hypoxia, whereas CD11c, CD14, CD123, CD49
      and HLA-DR expression remained unaltered in DCs cultured in hypoxia or normoxia.
      DC secretion of IL-12p70, the bioactive interleukin-12 (IL-12), a cytokine
      produced in response to inflammatory mediators, was enhanced under hypoxia. In
      addition, phagocytic activity (Leishmania uptake) was not impaired under hypoxia,
      although this microenviroment induced infected DCs to reduce parasite survival,
      consequently controlling the infection rate. All these data support the notion
      that a hypoxic microenvironment promotes selective pressure on DCs to assume a
      phenotype characterized by pro-inflammatory and microbial activities in injured
      or inflamed tissues and contribute to the innate immune response.

PMID- 20132175
TI  - Inducible nitric oxide synthase expression and its prognostic significance in
      colorectal cancer.
AB  - Nitric oxide synthases (NOS) are expressed in colorectal cancer. The aim of this
      study was to examine the inducible NOS (iNOS) expression in colorectal cancer and
      to investigate its prognostic relevance. Tissue sections of primary tumors from
      132 patients undergoing curative resection for colorectal cancer were
      immunohistochemically examined for iNOS expression. The expression pattern of
      iNOS was correlated with various clinicopathological characteristics and
      survival. iNOS immunoreactivity was observed in the cytoplasm of tumor epithelial
      cells in 60 patients (45.5%) and positively correlated with lymph node
      involvement (p = 0.019). No significant correlation was found between iNOS
      expression and various clinicopathological characteristics, including age,
      gender, tumor location, tumor size, tumor grade, T stage, and Union International
      Contra la Cancrum (UICC) stage. Survival analysis showed a significant
      correlation between iNOS-positive tumors and poor disease-specific survival (p <
      0.0001), with independent prognostic significance in multivariate analysis (HR =
      4.42; p < 0.0001). Patients with stage II disease and iNOS-positive tumors had
      significantly worse disease-specific survival than those with iNOS-negative
      tumors (p < 0.0001). In addition, patients with stage III disease and iNOS
      positive tumors had significantly worse disease-specific survival than those with
      iNOS-negative tumors (p = 0.001). The ability of iNOS to predict outcome in
      colorectal cancer patients may be independent of other known prognostic factors,
      providing a new molecular marker with significant potential for clinical utility.

PMID- 20132176
TI  - Bacteriocin production by Shigella sonnei isolated from faeces of children with
      acute diarrhoea.
AB  - Shigella is a common agent of diarrhoea, a worldwide major health problem. The
      bacterium produces bacteriocins; however, the role of these substances as a
      virulence factor is completely unknown. With the aim to search for colicin
      production by Shigella sonnei, to evaluate the influence of culture conditions on
      bacteriocin expression, and to characterize the substance partially, 16 S. sonnei
      strains isolated from children with diarrhoea were tested for antagonism against
      members of the intestinal microbiota or agents of diarrhoea. Nine strains
      exhibited isoantagonism and heteroantagonism against S. flexneri and
      diarrhoeagenic Escherichia coli. Autoantagonism and antagonism against the
      intestinal microbiota were not detected. Culture medium and incubation conditions
      influenced antagonism expression. Antagonism resulting from bacteriophages, low
      pH, fatty acids, hydrogen peroxide, and chloroform was excluded. The activity of
      the intracellular fraction obtained with 75% ammonium sulphate was preserved at
      pH 1.0-11.0, and was found to be reduced by organic solvents and affected by high
      temperatures and proteases. The antagonistic spectrum and the in vitro conditions
      for better antagonism expression suggest that the role of colicin in S. sonnei
      virulence, if any, would be expressed prior to infection, and may regulate
      population density of enteropathogens by helping in organism transmission.

PMID- 20132177
TI  - Salmonella or Campylobacter gastroenteritis prior to a cancer diagnosis does not
      aggravate the prognosis: a population-based follow-up study.
AB  - We hypothesized that preceding zoonotic Salmonella or Campylobacter
      gastroenteritis aggravated the prognosis in cancer patients. Exposed patients
      comprised all of those diagnosed with first-time Salmonella/Campylobacter
      gastroenteritis from 1991 and with first-time cancer diagnosis thereafter
      (through 2003) in two Danish counties. These patients were matched for main
      cancer type, gender, age and calendar period to unexposed cancer patients, i.e.
      those without Salmonella/Campylobacter gastroenteritis. We compared cancer stage
      by age- and comorbidity-adjusted logistic regression analysis, survival by
      comorbidity-adjusted Cox's regression analysis and mortality dependent on the
      time period between Salmonella/Campylobacter gastroenteritis and cancer by spline
      regression curves. The study cohort comprised 272 Salmonella/Campylobacter
      exposed cancer patients and 2681 unexposed cancer patients. Prevalence odds
      ratios [95% confidence intervals (CI)] in exposed as compared with unexposed
      patients were 0.96 (0.74-1.25) for localized tumours, 1.15 (0.87-1.54) for
      regional spread and 1.14 (0.84-1.55) for metastases. Adjusted mortality rate
      ratios (95% CI) were 0.93 (0.75-1.16) for 0-1 year, 1.08 (0.84-1.39) for 2-5
      years and 1.02 (0.60-1.73) for the remaining period. Mortality estimates did not
      change in relation to the time period between gastroenteritis and cancer.
      Salmonella/Campylobacter gastroenteritis prior to cancer was associated with
      neither the cancer stage nor a poorer prognosis.

PMID- 20132178
TI  - Toxic activity of the CdtB component of Haemophilus ducreyi cytolethal distending
      toxin expressed from an adenovirus 5 vector.
AB  - The Haemophilus ducreyi cytolethal distending toxin (HdCDT) catalytic subunit
      CdtB has DNase-like activity and mediates DNA damage after its delivery into
      target cells. We constructed a replication-deficient adenovirus type 5 (Ad5)
      vector expressing CdtB and investigated the toxic properties of this vector on
      HeLa cells. Ad5CdtB caused loss of cell viability, morphologic changes, and cell
      cycle arrest, findings similar to HdCDT intoxication. This confirmed that CdtB is
      responsible for the toxicity of the holotoxin when expressed in cells following
      transduction by an adenoviral vector, and indicated a possible potential of this
      novel strategy in studies of activity of intracellular products and in gene
      therapy of cancer.

PMID- 20132179
TI  - Cytopathologic differential diagnosis of small cell carcinoma and poorly
      differentiated non-small cell carcinoma in bronchial lavage specimens using a
      regression analysis.
AB  - The aim of this study was to determine the most significant cytologic features to
      differentiate small cell carcinoma (SCC) from poorly differentiated non-small
      cell carcinoma (NSCC) in bronchial lavage specimens. Bronchial lavage specimens
      from 35 SCC cases and 63 poorly differentiated NSCC cases were examined and the
      cytologic parameters reviewed retrospectively. Thirty-five cytologic features
      considered useful in differential diagnosis were assessed. Statistical analysis
      indicated that salt and pepper chromatin, small cell size and nuclear molding
      have more than 90% sensitivity and 70% specificity for SCC cases. Logistic
      regression analysis demonstrated that the most effective criteria to
      differentiate SCC from poorly differentiated NSCC are small cell size, salt and
      pepper chromatin, prominent nucleolus and papilla formation. When these selected
      variables were used, sensitivity for predicting SCC was 94.3% and specificity
      96.8%, and sensitivity for predicting NSCC was 96.8% and specificity 94.3%. There
      are several cytologic features, which are highly sensitive and specific for
      distinguishing SCC from NSCC. Nuclear features such as chromatin pattern, and
      size of the nucleoli and nuclei are more valuable than cytoplasmic features to
      distinguish between the two.

PMID- 20132180
TI  - An in vitro model of bacterial infections in wounds and other soft tissues.
AB  - There is growing evidence that bacteria play a crucial role in the persistence of
      chronic wounds. These bacteria are most probably present in polymer-embedded
      aggregates that represent the biofilm mode of growth. Much work has been carried
      out to study the development of biofilms in vitro, in particular in attachment to
      solid surfaces. The observations from the chronic wounds indicate that the
      bacteria are not attached to a solid surface. Consequently, a new in vitro model
      is required to investigate biofilms in more wound-like settings. This study
      describes such a novel in vitro model, with bacteria growing as biofilm
      aggregates in a collagen gel matrix with serum protein mimicking the wound bed of
      chronic wounds. The model was verified to comprise important hallmarks of
      biofilms such as the bacterial embedment in a matrix and increased antibiotic
      tolerance. Furthermore, we have verified the relevance of the model by comparing
      the organization of the bacteria in the model with the organization of the
      bacteria in a real chronic wound. We believe that we have developed an important
      new model for investigating bacterial biofilms in chronic wounds. This model may
      be used to study biofilm development in chronic wounds and to develop novel
      diagnostic tools as well as treatment strategies.

PMID- 20132181
TI  - Signet-ring cell follicular adenoma of the thyroid.

PMID- 20132182
TI  - Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from
      pharyngitis patients.
AB  - Streptococcal toxic shock syndrome (STSS) is a re-emerging infectious disease in
      Japan and many other developed countries. Epidemiological studies have revealed
      that the M1 serotype of Streptococcus pyogenes is the most dominant causative
      isolate of STSS. Recent characterization of M1 isolates revealed that the
      mutation of covS, one of the two-component regulatory systems, plays an important
      role in STSS by altering protein expression. We analyzed the M1 S. pyogenes
      clinical isolates before or after 1990 in Japan, using two-dimensional gel
      electrophoresis (2-DE) and pulsed-field gel electrophoresis (PFGE). PFGE profiles
      were different between the isolates before and after 1990. Markedly different
      profiles among isolates after 1990 from STSS and pharyngitis patients were
      detected. Sequence analysis of two-component regulatory systems showed that covS
      mutations were detected not only in STSS but also in three pharyngitis isolates,
      in which proteins from the culture supernatant displayed the invasive type. The
      mutated CovS detected in the pharyngitis isolates had impaired function on the
      production of streptococcal pyrogenic exotoxin B (SpeB) analyzed by 2-DE. These
      results suggest that several covS mutations that lead to the malfunction of the
      CovS protein occurred even in pharyngeal infection.

PMID- 20132183
TI  - Sub-lethal heat shock induces plasma membrane translocation of 70-kDa heat shock
      protein in viable, but not in apoptotic, U-937 leukaemia cells.
AB  - Heat shock protein 70 kDa, Hsp70, is an important intracellular factor that
      protects cells from stress. Unusual plasma membrane expression of Hsp70, observed
      in some cancer cells, contributes to the cell's recognition and elimination by
      the immune system. Induction of apoptosis in cancer cells was demonstrated to
      increase Hsp70 translocation to the surface membrane, enhancing immunogenic
      effects through the stimulation of dendritic cells. As hyperthermia is proposed
      as a method of choice for anti-cancer therapy, we examined whether apoptosis
      induction by heat shock enhances Hsp70 membrane translocation in U-937 leukaemia
      cells. Cells were exposed to sub-lethal heat shock, and intracellular and
      membrane-bound Hsp70 expression was evaluated in apoptotic and viable cell sub
      populations, employing flow cytometry and immunofluorescence. Heat shock induced
      Hsp70 membrane translocation in the viable cells that were able to enhance Hsp70
      production upon heating, but not in the cells undergoing apoptosis that continued
      to express low basal levels of the intracellular protein. Data suggest that the
      protein translocation was associated with the increasing Hsp70 content rather
      than the apoptotic process. Apoptosis does not contribute to externalization of
      Hsp70, at least in the cells with low levels of this protein.

PMID- 20132184
TI  - Overexpression of TrkB promotes the progression of colon cancer.
AB  - Studies have confirmed that TrkB plays important roles in facilitating metastasis
      in various types of malignant tumors. In the present study, 30 cases of colon
      cancer and matched non-tumors were examined for the expression of TrkB by Western
      blot. The expression of TrkB was also examined in 90 colon tumor sections by
      immunohistochemical methods, and D2-40 staining was used to evaluate the
      correlation between TrkB expression and lymphatic vessel density. To investigate
      the effects of TrkB on the progression of colon cancer, siRNA specific for TrkB
      was transfected into LoVo cells, and proliferation, apoptosis and invasion of
      transfected cells were examined using MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide], flow cytometry and Transwell assays, respectively.
      Our results showed that TrkB was up-regulated in colon tumors compared with the
      non-tumorous counterparts, and the overexpression of TrkB was closely correlated
      with lymphatic vessel density (LVD) and metastasis. Inhibition of TrkB by siRNA
      increased the apoptotic rates of transfected cells, while the numbers of
      proliferative and invasive cells were decreased. In summary, our data suggest
      that overexpression of TrkB in colon cancer possibly plays roles in inhibiting
      apoptosis, promoting proliferation and invasion, facilitating tumor progression
      by lymphangiogenesis-associated metastasis.

PMID- 20132185
TI  - Enhancer of zeste homolog 2 expression is associated with tumor cell
      proliferation and metastasis in gastric cancer.
AB  - The enhancer of zeste homolog 2 (EZH2), a member of the polycomb group of
      proteins, plays an important role in cell proliferation and cell cycle
      regulation. EZH2 is overexpressed in aggressive forms of prostate, breast,
      bladder, and endometrial cancers. However, the role of EZH2 expression in gastric
      cancer has not been fully determined. This study was conducted to investigate the
      correlation between EZH2 and cell cycle-related molecules, and the clinical value
      of EZH2 expression in gastric cancer. We analyzed EZH2 expression using Western
      blotting in AGS, MKN-28, SNU-16, SNU-484, SNU-601, and SNU-638 gastric cancer
      cell lines. After transfection of EZH2 siRNA into MKN-28 cells, the change in
      cell cycle-related molecules was assessed by Western blot analysis. Expression of
      EZH2, Ki-67, and p53 was determined by immunohistochemical staining of tissue
      microarrays from specimens of 137 cases of resected gastric cancer. We found high
      expressions of EZH2 in all of the tested gastric cancer cell lines. RNA
      interference of EZH2 induced upregulation of p53 and HDAC1 and downregulation of
      cyclin D1 and cyclin E. High EZH2 expression was observed in 60.6% of gastric
      cancers and in 6.7% of non-neoplastic gastric tissues (p < 0.01); 40.1% were
      positive for p53 in gastric cancers. High EZH2 expression was correlated with Ki
      67 and p53 expressions and was significantly associated with distant metastases
      and non-signet ring cells. Our results suggest that high EZH2 expression is
      associated with tumor cell proliferation and metastasis in gastric cancer.

PMID- 20132186
TI  - Assessment of RNA amplification by multiplex RT-PCR and IgM detection by indirect
      and capture ELISAs for the diagnosis of measles and rubella.
AB  - The aim of the study was to compare RNA amplification using multiplex RT-PCR and
      IgM detection by means of indirect and capture ELISAs for the diagnosis of
      measles and rubella. A total of 229 cases of maculopapular rash with serum and
      throat swab samples were included. Specific serological IgM to measles and
      rubella was determined by Enzygnost (Siemens) and Platelia (Bio-Rad). Both
      viruses were researched using multiplex RT-PCR performed on throat samples.
      Criteria for inclusion of measles or rubella cases were a positive RT-PCR result
      for one virus and negative for the other; and/or a positive IgM result for one
      virus by both ELISAs and negative RT-PCR for the other virus. A total of 74 cases
      were classified as measles and 54 as rubella. In measles, sensitivity and
      specificity were 93.2% and 100% for RT-PCR, 97.3% and 98.1% for Enzygnost, and
      90.5% and 95.5% for Platelia. For rubella, these values were 42.6% and 100% for
      RT-PCR, 100% and 97.1% for Enzygnost, and 94.4% and 98.3% for Platelia. Enzygnost
      and Platelia are useful techniques for detecting IgM against measles and rubella.
      RNA amplification by RT-PCR was both sensitive and specific for the diagnosis of
      measles; however, for rubella, the sensitivity of this technique must be
      improved.

PMID- 20132187
TI  - Evaluation of coxsackievirus and adenovirus receptor expression in human benign
      and malignant thyroid lesions.
AB  - Coxsackievirus and adenovirus receptor (CAR) expression on tumor cells is
      associated with sensitivity to adenoviral infection, being considered as a
      surrogate marker for monitoring and/or predicting adenovirus-mediated gene
      therapy. The aim of this study was to evaluate the clinical significance of CAR
      expression in human benign and malignant thyroid lesions. CAR protein expression
      was assessed immunohistochemically on paraffin-embedded thyroid tissues from 107
      patients with benign and malignant lesions and was statistically analyzed in
      relation to histopathologic type; tumor size; lymph node metastasis; capsular,
      lymphatic and vessel invasion; as well as follicular cells' proliferative
      capacity. CAR immunoreactivity was characterized as negative/weak in 53 (49.53%),
      moderate in 31 (28.97%) and strong in 23 (21.50%) of 107 thyroid cases. CAR
      immunoreactivity was significantly increased in malignant compared with that in
      benign thyroid lesions (p = 0.00002). Both malignant and benign thyroid lesions
      with enhanced follicular cells' proliferative capacity showed significantly
      increased CAR immunoreactivity (p = 0.00027). In malignant thyroid lesions,
      enhanced CAR immunoreactivity was significantly associated with larger tumor size
      (p = 0.0067). The current data revealed that CAR immunoreactivity could be
      considered of diagnostic utility in thyroid neoplasia. Further research effort is
      warranted to delineate whether CAR could be considered clinically important for
      both diagnosis and future (gene) therapeutic applications in thyroid neoplasia.

PMID- 20132188
TI  - Mitotic arrest defective protein 2 expression abnormality and its
      clinicopathologic significance in human osteosarcoma.
AB  - Osteosarcoma is the most common primary malignancy of bone. Overexpression of
      mitotic arrest defective protein 2 (MAD2) is found in many human neoplasms, but
      its role in the oncogenesis of osteosarcoma is an untouched topic. The objective
      of this research was to observe the expression of MAD2 in human osteosarcoma and
      explore its clinicopathologic significance. MAD2 expression was analyzed in 48
      primary osteosarcoma cases (19 osteoblastic osteosarcomas, 17 chondroblastic
      osteosarcomas and 12 fibroblastic osteosarcomas) using immunohistochemistry. A
      total of 20 normal bone specimens formed a control group. MAD2 was commonly
      overexpressed in human osteosarcoma. Immunopositivity was higher in tumors with
      lower differentiation and higher clinical stage. Increased expression of MAD2 was
      associated with earlier metastasis and poorer survival. Our findings provide
      evidence that MAD2 contributes to the pathogenesis and development of human
      osteosarcoma, Testing may have a clinical role in predicting prognosis, selecting
      appropriate chemotherapeutic strategies and providing novel strategies for
      osteosarcoma therapy.

PMID- 20132189
TI  - Diversity of Veillonella spp. from subgingival plaque by polyphasic approach.
AB  - In a biofilm such as the subgingival microflora, strain-specific properties or
      factors induced by the host may impart a survival advantage to some bacterial
      strains. Periodontal disease has been associated with chronic obstructive
      pulmonary disease (COPD) and we previously found high amounts of Veillonella in
      the subgingival microflora of COPD subjects. Differentiation of Veillonella is
      difficult. The aims of this study were to identify subgingival Veillonella
      isolates by phenotypic, genetic typing and molecular genetic methods, and
      further, to assess if Veillonella strain properties or identity correlated with
      periodontal disease or COPD. From 22 subjects, 26 subgingival Veillonella
      isolates and one pulmonary isolate were analysed. The majority of the subgingival
      Veillonella isolates were identified as Veillonella parvula. Genotyping showed
      heterogeneity within strains of the same species. A subgingival and pulmonary
      isolate in one COPD subject was found to be genetically identical strains of V.
      parvula. Scanning electron microscopy of the lung biopsy confirmed single small
      cocci adhering or coaggregating with larger cocci on the airway epithelium. Apart
      from a variation in cellular fatty acid composition of six subgingival isolates
      from periodontitis subjects, no correlation between the subgingival Veillonella
      strains or genotypes and the presence of either periodontitis or COPD was found.
      In conclusion, V. parvula was the predominant subgingival Veillonella species
      with high genetic variability within strains of the same species. Subgingival V.
      parvula can translocate to the lungs; however, Veillonella identity or genotype
      did not correlate with periodontal disease or COPD.

PMID- 20132191
TI  - Respect for autonomy, advance directives, and minimally conscious state.
AB  - In this article, I consider whether the advance directive of a person in
      minimally conscious state ought to be adhered to when its prescriptions conflict
      with her current wishes. I argue that an advance directive can have moral
      significance after its issuer has succumbed to minimally conscious state. I also
      defend the view that the patient can still have a significant degree of autonomy.
      Consequently, I conclude that her advance directive ought not to be applied. Then
      I briefly assess whether considerations pertaining to respecting the patient's
      autonomy could still require obedience to the desire expressed in her advance
      directive and arrive at a negative answer.

PMID- 20132192
TI  - Abortion counselling and the informed consent dilemma.
AB  - An obstacle to abortion exists in the form of abortion 'counselling' that
      discourages women from terminating their pregnancies. This counselling involves
      providing information about the procedure that tends to create feelings of guilt,
      anxiety and strong emotional reactions to the recognizable form of a human fetus.
      Instances of such counselling that involve false or misleading information are
      clearly unethical and do not prompt much philosophical reflection, but the
      prospect of truthful abortion counselling draws attention to a delicate issue for
      healthcare professionals seeking to respect patient autonomy. This is the fact
      that even accurate information about abortion procedures can have intimidating
      effects on women seeking to terminate a pregnancy. Consequently, a dilemma arises
      regarding the information that one ought to provide to patients considering an
      abortion: on the one hand, the mere offering of certain types of information can
      lead to intimidation; on the other hand, withholding information that some
      patients would consider relevant to their decision-making is objectionably
      paternalistic on any standard account of the physician-patient relationship. This
      is an unsettling conclusion for the possibility of setting fixed professional
      guidelines regarding the counselling offered to women who are considering
      abortion. Thus, abortion ought to be viewed as an illuminating example of a
      procedure for which the process of securing informed consent ought to be highly
      context-sensitive and responsive to the needs of each individual patient. This
      result underscores the need for health care professionals to cultivate trusting
      relationships with patients and to develop finely tuned powers of practical
      judgment.

PMID- 20132193
TI  - Triangular reflective equilibrium: a conscience-based method for bioethical
      deliberation.
AB  - Following a discussion of some historical roots of conscience, we offer a
      systematized version of reflective equilibrium. Aiming at a comprehensive
      methodology for bioethical deliberation, we develop an expanded variant of
      reflective equilibrium, which we call 'triangular reflective equilibrium' and
      which incorporates insights from hermeneutics, critical theory and narrative
      ethics. We focus on a few distinctions, mainly between methods of justification
      in ethics and the social practice of bioethical deliberation, between coherence
      in ethical reasoning, personal integrity and consensus formation, and between
      political and moral deliberation. The ideal of deliberation is explicated as a
      sharing of conscience within a special commitment to sincerity and openness to
      persuasion. Personal growth in wisdom is an indirect by-product of the continuous
      practice of moral deliberation. This is explicated in the light of Sternberg's
      balance theory of wisdom and in the context of medicine as a profession embodying
      altruistic responsibilities of care in democratic and pluralistic societies.

PMID- 20132194
TI  - Parental love pills: some ethical considerations.
AB  - It may soon be possible to develop pills that allow parents to induce in
      themselves more loving behaviour, attitudes and emotions towards their children.
      In this paper, I consider whether pharmacologically induced parental love can
      satisfy reasonable conditions of authenticity; why anyone would be interested in
      taking such parental love pills at all, and whether inducing parental love
      pharmacologically promotes narcissism or results in self-instrumentalization. I
      also examine how the availability of such pills may affect the duty to love a
      child.

PMID- 20132195
TI  - International validation of the prognostic value of lymphovascular invasion in
      patients treated with radical cystectomy.
AB  - OBJECTIVE: To externally validate the prognostic value of lymphovascular invasion
      (LVI) in a large international cohort of patients treated with radical cystectomy
      (RC) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: We
      collected data from 4257 patients treated with RC and pelvic lymphadenectomy for
      UCB, without neoadjuvant chemotherapy, at 12 centres. LVI was defined as presence
      of nests of tumour cells within an endothelium-lined space. RESULTS: LVI was
      detected in 1407 patients (33.1%); the proportion of LVI increased with advancing
      stage, higher grade, soft-tissue surgical margin involvement, and lymph node
      metastasis (P < 0.001 for all). In standard multivariate models, LVI was
      associated with both disease recurrence (hazard ratio 1.43, P < 0.001) and cancer
      specific mortality (1.45, P < 0.001). In the entire cohort, adding LVI to a base
      model that included standard features improved only minimally its predictive
      accuracy for both recurrence and cancer-specific mortality (by 1.1% and 1.2%,
      respectively). In 3122 patients with negative lymph nodes, LVI remained
      independently associated with and improved the predictive accuracy of the
      standard predictors for recurrence (hazard ratio 1.68, P < 0.001; +2.3%) and
      cancer-specific mortality (1.70, P < 0.001; +2.4%). By contrast, in 1071 node
      positive patients, LVI only marginally improved the prediction of cancer-specific
      recurrence (hazard ratio 1.20, P < 0.001; +0.2%) and survival (1.23, P < 0.001;
      +0.5%). CONCLUSIONS: LVI is strongly associated with clinical outcome in node
      negative patients treated with RC. The assessment of LVI might help to identify
      patients who could benefit from adjuvant therapy after RC. After confirmation in
      different populations, LVI should be included in the staging of UCB.

PMID- 20132196
TI  - Nuclear factor-kappaB activation predicts an unfavourable outcome in human upper
      urinary tract urothelial carcinoma.
AB  - OBJECTIVE: to examine the hypothesis that nuclear factor-kappaB (NF-kappaB), a
      transcription factor involved in anti-apoptosis, invasion, and angiogenesis,
      plays a role in the carcinogenesis of upper urinary tract urothelial carcinoma
      (UUT-UC) and has prognostic value for survival. PATIENTS AND METHODS: in all, 90
      patients with UUT-UC [mean (range) age, 64.5 (24-84) years] who underwent surgery
      at our institution from January 1991 to December 2005 were included.
      Clinicopathological data were collected retrospectively. We performed
      immunohistochemical staining for NF-kappaB (p65) on paraffin-embedded sections of
      the tumour and corresponding normal tissues. The association between survival and
      potential prognostic factors was examined. RESULTS: the median follow-up was 40
      months. In all, 55 patients (61.1%) with UUT-UC overexpressed cytoplasmic NF
      kappaB, and nuclear immunoreactivity for NF-kappaB was detected in 24 patients
      (26.7%). On univariate analysis, significant prognostic factors for survival were
      tumour location, stage, grade, lymph node involvement, and nuclear NF-kappaB
      expression. On multivariate analysis, nuclear NF-kappaB positivity was an
      independent predictor for disease-specific survival [Cox regression hazard ratio
      (HR) 2.87; P= 0.025] and overall survival (HR 2.24; P= 0.037). CONCLUSION: these
      results imply a role for nuclear NF-kappaB expression in the tumorigenesis of UUT
      UC. Nuclear NF-kappaB may serve as a useful independent molecular marker to
      predict outcome and may represent a promising therapeutic target for patients
      with UUT-UC.

PMID- 20132197
TI  - Laparoscopic artificial urinary sphincter implantation for female genuine stress
      urinary incontinence: technique and 4-year experience in 25 patients.
AB  - OBJECTIVE: to assess the safety, feasibility and efficacy of laparoscopic
      implantation of the artificial urinary sphincter (AUS) in women with genuine
      stress urinary incontinence (SUI). PATIENTS AND METHODS: from April 2005 to July
      2009, 25 women (mean age 66.8 years) with genuine SUI had a laparoscopic
      implantation of the AUS (AMS 800(TM) , American Medical Systems, Minnetonka, MN,
      USA). Patients had a negative Marshall test and urodynamic studies showed
      decreased closure pressure. All patients had a history of urogynaecological
      surgery. Transperitoneal laparoscopic access was created with two midline 10-mm
      and two lateral 5-mm trocars. One of the lateral port incisions was later
      extended to facilitate urethrovaginal dissection with scissors and dissector, and
      the insertion and assembly of the AUS. In six cases of concomitant genito-urinary
      prolapse, laparoscopic anterior and posterior mesh promontofixation was also
      performed. RESULTS: the AUS was successfully implanted in all cases with no
      conversion to open surgery. There were no intra- or perioperative complications,
      except one vaginal perforation which was repaired during surgery. The mean
      operative duration was 92 min (71 min without and 123 min with simultaneous
      promontofixation). Five patients developed urinary retention, which was managed
      with re-insertion of the urethral catheter for 2 days in four and with insertion
      of a suprapubic catheter for 4 weeks in a patient with spina bifida. During the
      mean follow-up of 26.1 months, two treatment failures were diagnosed due to
      vaginal erosion and were managed with removal of the AUS. All the remaining 23
      patients reported continence, either complete (in 19) or social (in four).
      However, this was not a randomized comparative study. CONCLUSION: laparoscopic
      implantation of the AUS in women with genuine SUI is safe, feasible and
      efficient.

PMID- 20132198
TI  - Chronic alcoholism associated with diabetes impairs erectile function in rats.
AB  - OBJECTIVE: To investigate the effects of chronic ethanol consumption and diabetes
      on nitric oxide (NO)-mediated relaxation of cavernosal smooth muscle (CSM).
      MATERIAL AND METHODS: Male Wistar rats were divided into four groups: control,
      isocaloric, diabetic and ethanol-diabetic. The CSMs were mounted in organ
      chambers for measurement of isometric tension. Contraction of the strips was
      induced by electrical field stimulation (EFS, 1-32 Hz) and phenylephrine. We also
      evaluated the effect of ethanol consumption on the relaxation induced by
      acetylcholine (ACh; 0.01-1000 micromol/L), sodium nitroprusside (SNP, 0.01-1000
      micromol/L) or EFS (1-32 Hz) in strips pre-contracted with phenylephrine (10
      micromol/L). Immunoexpression of endothelial NO synthase (eNOS) and inducible NOS
      (iNOS) was also accessed. RESULTS: The endothelium-dependent relaxation induced
      by ACh was decreased in CSM from ethanol-diabetic rats when compared with the
      controls, with a mean (sem) of 21 (4) vs 37 (2)%. Similarly, the potency and
      maximal responses induced by SNP were reduced in the ethanol-diabetic [3.97
      (0.38) and 85 (1)%, respectively] and diabetic groups [3.78 (0.56) and 81 (2)%,
      respectively] when compared with the controls [5.3 (0.22) and 90 (3)%,
      respectively] and isocaloric [5.3 (0.19) and 92 (1)%, respectively] groups.
      Noradrenergic nerve-mediated contractions of CSM in response to EFS were
      increased in rats from ethanol-diabetic and diabetic groups when compared with
      the control and isocaloric groups. Conversely, there were no differences in EFS
      induced relaxation among the groups. The immunostaining assays showed
      overexpression of eNOS and iNOS in the CSM from diabetic and ethanol-diabetic
      rats when compared with the control and isocaloric rats. CONCLUSION: There was an
      impairment of relaxation of CSM from ethanol-diabetic and diabetic rats that
      involved a decrease in the NO-cyclic guanosine monophosphate signalling pathway
      by endothelium-dependent mechanisms accompanied by a change in the CSM
      contractile sensitivity.

PMID- 20132199
TI  - Ischaemia-reperfusion injury in renal transplantation: the role of nitric oxide
      in an experimental rat model.
AB  - OBJECTIVE: to investigate the role of nitric oxide (NO) in ischaemia-reperfusion
      (I/R) injury in a renal transplant rat model, as I/R injury is a common
      consequence of renal transplantation and NO has many protective properties that
      might protect the kidney after I/R injury. MATERIALS AND METHODS: in all, 30 male
      Sprague-Dawley rats weighing 350-400 g and aged 4-6 months underwent renal
      transplantation and received FK506 (an immunosuppressant) to overcome early acute
      rejection episodes. The rats were divided randomly into three groups (10 rats
      each): Group I, treated with FK506 (2 mg/kg body weight [bw], once daily), served
      as the control group; Group II, treated with FK506 2 mg/kg bw and L-arginine 300
      mg/kg bw; and Group III, treated with FK506 (2 mg/kg bw) and, n-omega-nitro-l
      arginine methyl ester (L-NAME; 50 mg/kg bw). Urine and blood samples were taken
      at 0 (before operation), 2, 7, and 14 days after transplantation for estimation
      of urine sodium, creatinine, fractional excretion of sodium, serum creatinine,
      sodium, and blood urea nitrogen (BUN). Kidney specimens were taken for
      histological examination by light microscopy. RESULTS: serum creatinine and BUN
      levels significantly decreased in the L-arginine-treated group (both P < 0.001)
      while they were significantly increased in the L-NAME-treated group (P < 0.005
      and P < 0.001, respectively) compared with the control group at all time
      intervals. Light microscopic examination of the renal biopsies in the control
      group showed acute tubular necrosis, which was minimal in kidneys transplanted
      and treated with L-arginine and more markedly with L-NAME. CONCLUSION: I/R injury
      impaired graft function during the first week after transplantation. Injection of
      L-arginine before ischaemia antagonized graft deterioration and improved
      morphological appearance.

PMID- 20132200
TI  - Expression and prognostic value of platelet-derived growth factor-AA and its
      receptor alpha in nephroblastoma.
AB  - OBJECTIVE: To investigate the potential role of platelet-derived growth factor-AA
      (PDGF-AA) and the PDGF-alpha receptor as prognostic markers in Wilms' tumour.
      PATIENTS AND METHODS: The expression of PDGF-AA and PDGF-alpha were investigated
      using immunohistochemical analysis of 62 Wilms' tumours. Patients were treated
      with chemotherapeutic agents before surgery and had a mean follow-up of 6.4
      years. RESULTS: PDGF-AA and PDGF-alpha were expressed by the mesenchymal tissue
      of the normal kidney and mainly detected in the epithelial component of Wilms'
      tumour. Immunoreactive tumour epithelium cells were found in 50% and 55% for PDGF
      AA and PDGF-alpha, respectively. The epithelial expression of both PDGF-AA and
      PDGF-alpha correlated with pathological stage. Univariate analysis showed that
      epithelial PDGF-AA and PDGF-alpha receptor expression were indicative of clinical
      progression. In a multivariate analysis, PDGF-alpha protein expression by
      epithelial cells was an independent prognostic marker of a favourable prognosis.
      CONCLUSIONS: Expression of both PDGF-AA and PDGF-alpha in the epithelial part of
      Wilms' tumour correlated with tumour stage and clinical progression. Our data
      suggest that both PDGF-AA and PDGF-alpha receptor expression are related to
      prognosis.

PMID- 20132201
TI  - Long-term outcome of tension-free vaginal tape for treating stress incontinence
      in women with neuropathic bladders.
AB  - OBJECTIVE: To evaluate the long-term safety and efficacy of the tension-free
      vaginal tape (TVT) for the treatment of stress urinary incontinence (SUI) in
      women with neuropathic bladder dysfunction. PATIENTS AND METHODS: Twelve women
      (mean age 53.3 years, range 41-80) with neuropathic bladder dysfunction and SUI
      confirmed by video-cystometrography (VCMG) were treated with a TVT in one
      institution by an expert neuro-urologist between November 1997 and December 2000.
      The patient's notes, clinical annual follow-up and VCMG after the procedure, and
      the incontinence impact questionnaire (IIQ) forms (Urinary Distress Inventory,
      and IIQ-7) were assessed during the long-term clinical follow-up for SUI, in
      addition to a health-related quality of life assessment. The cure of SUI was
      defined as no loss of urine on physical exercise, confirmed VCMG after the
      procedure, and by clinical assessment. RESULTS: The mean (range) follow-up was 10
      (8.5-12) years. Nine patients were using clean intermittent self-catheterization
      before the insertion of TVT and continued to do so afterward. At 10 years of
      follow-up, one patient had died (with failed TVT initially), and two were lost to
      follow-up at 5 years after surgery, but up to 5 years they did not complain of UI
      and VCMG did not show SUI. The remaining seven of the nine patients were
      completely dry, and two improved and were satisfied with using one or two
      pads/day. Two patients showed neurogenic detrusor overactivity confirmed on VCMG,
      with no evidence of SUI. One patient needed a transient urethral catheter for
      urinary retention after surgery, one had a bladder injury that required leaving
      the catheter for 5 days, but no urethral erosions were reported during the follow
      up. CONCLUSIONS: In women with neuropathic bladder dysfunction secondary to a
      variety of spinal cord pathologies, and who have SUI necessitating a definitive
      intervention, insertion of TVT should be considered a desirable treatment, with
      very good long-term outcomes.

PMID- 20132202
TI  - Extended vs standard pelvic lymphadenectomy during laparoscopic radical
      prostatectomy for intermediate- and high-risk prostate cancer.
AB  - OBJECTIVE: To investigate the effect of extended vs standard pelvic
      lymphadenectomy (sPLND) for patients with intermediate- and high-risk prostate
      cancer undergoing laparoscopic radical prostatectomy (LRP). PATIENTS AND METHODS:
      Of a total of 1269 patients who underwent LRP during a 109 month period, 374
      (30%) had a PLND; 253 men had a sPLND (2000 to March 2008) and 121 had an
      extended PLND (ePLND; after April 2008) for intermediate- or high-risk prostate
      cancer. An extraperitoneal approach was used in all patients having sPLND and a
      transperitoneal approach in patients having ePLND. RESULTS: Patient age, body
      mass index, gland weight, prostate-specific antigen level and Gleason grade were
      similar in the two groups. The ePLND group had a greater proportion of patients
      with cT3 disease (9.9% vs 4.2%, P = 0.046) and was associated with a longer
      operating time of 206.5 vs 180.0 min (P < 0.001) and a higher node count of 17.5
      vs 6.1 (P = 0.002). Blood loss, hospital stay, transfusion and complication rates
      were similar in the two groups. Lymph node positivity was significantly greater
      (P = 0.018) in patients with pathological Gleason grade 7 tumours who had ePLND
      (9.6% vs 1.0%) but was similar for other grades of tumour. CONCLUSION: Based on
      these findings, and the results of other studies which show a reduction of
      prostate cancer-specific mortality of 23% if lymph nodes are positive and 15% if
      they are negative after ePLND, and the correlation between surgical experience,
      lymph node yield and positivity, we recommend that all patients undergo ePLND if
      they are being treated with curative intent for intermediate- and high-risk
      prostate cancer; ePLND should replace sPLND and surgeons performing <35 cases of
      RP a year should stop performing RP.

PMID- 20132203
TI  - The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate
      release, propiverine, tolterodine extended-release and tolterodine immediate
      release in the treatment of patients with overactive bladder in the UK National
      Health Service.
AB  - OBJECTIVE: To assess the cost-effectiveness of solifenacin vs other
      antimuscarinic strategies commonly used in UK clinical practice, based on the
      results of a recent published review. METHODS: Overactive bladder (OAB) syndrome
      is characterized by symptoms of urgency, frequency, incontinence and nocturia.
      Pharmacological treatment comprises oral antimuscarinic agents, which are divided
      into older-generation treatments, including oxybutynin, and new-generation
      treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine.
      The latter have reduced central nervous system penetration and have better
      selectivity for the M3 subclass of acetylcholine receptors, resulting in improved
      tolerability. A recent systematic review and meta-analysis of the efficacy and
      safety of antimuscarinics provided an opportunity for an economic evaluation of
      these agents using a rigorous assessment of efficacy. A cost-utility analysis was
      undertaken using a 1-year decision-tree model. Treatment success was defined
      separately for urgency, frequency and incontinence, with efficacy data taken from
      the recent review. Treatment persistence rates were taken from the Information
      Management System database. Utility values for the calculation of quality
      adjusted life-years (QALYs) were taken from published sources. The analysis
      included costs directly associated with treatment for OAB, i.e. antimuscarinic
      therapy, consultations with general practitioners, and outpatient contacts.
      Resource use was based on expert opinion. Costs were reported at 2007/2008
      prices. Extensive deterministic and probabilistic analyses were conducted to test
      the robustness of the base-case results. RESULTS: Solifenacin was associated with
      the highest QALY gains (per 1000 patients) for all three outcomes of interest,
      i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was
      dominant relative to fesoterodine, tolterodine extended-release (ER) and
      tolterodine immediate-release (IR), and cost-effective relative to propiverine ER
      for urgency, frequency and incontinence. Solifenacin was not found to be cost
      effective relative to oxybutynin IR for the frequency and incontinence outcomes,
      with an incremental cost-effectiveness ratio of > pound30,000/QALY threshold.
      CONCLUSIONS: Solifenacin provided the greatest clinical benefit and associated
      QALYs for all three outcomes of interest across all therapies considered, and to
      be either dominant or cost-effective relative to all other new-generation agents,
      but not cost-effective relative to oxybutynin for frequency and incontinence.

PMID- 20132204
TI  - Expression of Snail1 in the fibrotic dermis of postmenopausal frontal fibrosing
      alopecia: possible involvement of an epithelial-mesenchymal transition and a
      review of the Japanese patients.

PMID- 20132205
TI  - CD4+/CD56+ TdT+ haematodermic neoplasm (previously called blastic natural killer
      cell lymphoma) in a patient with chronic human T-cell leukaemia virus type 1
      infection: a previously unreported association.

PMID- 20132206
TI  - Comparative molecular analysis of meticillin-resistant Staphylococcus aureus
      isolates from children with atopic dermatitis and healthy subjects in Taiwan.
AB  - BACKGROUND: Children with atopic dermatitis (AD) are more frequently colonized by
      Staphylococcus aureus than healthy children. OBJECTIVES: To assess whether any
      relationship exists between nasal meticillin-resistant S. aureus (MRSA)
      colonization and subsequent skin and soft-tissue infections (SSTI). PATIENTS AND
      METHODS: From 2005 through 2006, comparative molecular analyses of 23 MRSA
      colonizing isolates from 133 children with AD, 44 MRSA-colonizing isolates from
      490 healthy controls, and 12 MRSA-infecting isolates from 20 children with AD and
      concurrent SSTI were conducted. RESULTS: Nasal MRSA colonization in children with
      AD was significantly higher compared with normal individuals (17.3% vs. 9.0%; P =
      0.01). The molecular characteristics differed significantly between the MRSA
      isolates from children with AD and the MRSA-colonizing isolates from healthy
      controls. The clone characterized as sequence type (ST)59 (338)/pulsotype
      B/staphylococcal cassette chromosome mec (SCCmec) V(T)/Panton-Valentine
      leucocidin (PVL)-positive/staphylococcal enterotoxin B (SEB)-positive accounted
      for half of the MRSA isolates from children with AD, and another clone,
      characterized as ST59/pulsotype A/SCCmec IV/PVL-negative/SEB-positive accounted
      for 61% of the MRSA-colonizing isolates from healthy controls. CONCLUSIONS: We
      found MRSA colonizing the anterior nares of a large number of Taiwanese children,
      especially among those with AD. Analysis of our data provides evidence that links
      MRSA-colonizing isolates to MRSA-infecting isolates from concurrent SSTI in
      children with AD.

PMID- 20132207
TI  - Autosomal dominant multiple syringomas linked to chromosome 16q22.
AB  - BACKGROUND: The condition of multiple syringomas is a common skin problem that
      begins in early adulthood and is characterized by the appearance of skin-coloured
      papules around the eyes. Previous reports have demonstrated that some cases of
      multiple syringomas are inherited in an autosomal dominant manner. OBJECTIVE: To
      identify the genetic factors involved in the development of multiple syringomas.
      METHODS: We recruited seven families including multiple family members with
      multiple syringomas. Our sample included 24 affected individuals and 11
      unaffected individuals. We performed genome-wide single-nucleotide polymorphism
      screening for linkage analysis. RESULTS: Whole-genome screening and subsequent
      analysis revealed that all of the seven families were linked at a locus on
      chromosome 16q22. A significant logarithm of the odds score of 4.51 with theta of
      0.00 confirmed the mapping result. The analysis of critical recombinants defined
      the locus as a 6.63 cM interval in which 143 genes could be identified.
      CONCLUSIONS: We confirmed that the condition of multiple syringomas is an
      autosomal dominant disorder, and we determined the genomic location of the
      responsible gene.

PMID- 20132208
TI  - Ligand binding assays at equilibrium: validation and interpretation.
AB  - The focus of this review paper is factors affecting data interpretation in ligand
      binding assays under equilibrium conditions. Protocols for determining K(d) (the
      equilibrium dissociation constant) and K(dA) (the equilibrium inhibitor constant)
      for receptor ligands are discussed. The basic theory describing the interaction
      of a radiotracer and an unlabelled competitor ligand with a receptor is
      developed. Inappropriate experimental design may result in ligand depletion and
      non-attainment of equilibrium, distorting the calculation of K(d) and K(dA) .
      Strategies, both theoretical and practical, will be given to avoid and correct
      such errors, thus leading to the determination of reliable values for these
      constants. In determining K(dA) from competition binding studies, two additional
      concepts are discussed. First, the necessity to measure an adequate specific
      binding signal from the bound radiotracer ligand limits the range of affinity
      constants that can be measured: a particular set of assay conditions may lead to
      an upper limit on the apparent affinity of unlabelled ligands. Second, an
      extension of the basic assay methodology can indicate whether the interaction
      between the tracer and a test ligand is mediated by a competitive or an
      allosteric mechanism. Finally, the review ends with a discussion of two factors
      that are often overlooked: buffer composition and the temperature at which the
      assay is conducted, and the impact these can have on affinity measurements and
      the understanding of drug interactions.

PMID- 20132209
TI  - Ligand-directed signalling at beta-adrenoceptors.
AB  - beta-Adrenoceptors (ARs) classically mediate responses to the endogenous ligands
      adrenaline and noradrenaline by coupling to Gsalpha and stimulating cAMP
      production; however, drugs designed as beta-AR agonists or antagonists can
      activate alternative cell signalling pathways, with the potential to influence
      clinical efficacy. Furthermore, drugs acting at beta-ARs have differential
      capacity for pathway activation, described as stimulus trafficking, biased
      agonism, functional selectivity or ligand-directed signalling. These terms refer
      to responses where drug A has higher efficacy than drug B for one signalling
      pathway, but a lower efficacy than drug B for a second pathway. The accepted
      explanation for such responses is that drugs A and B have the capacity to induce
      or stabilize distinct active conformations of the receptor that in turn display
      altered coupling efficiency to different effectors. This is consistent with
      biophysical studies showing that drugs can indeed promote distinct conformational
      states. Agonists acting at beta-ARs display ligand-directed signalling, but many
      drugs acting as cAMP antagonists are also able to activate signalling pathways
      central to cell survival and proliferation or cell death. The observed complexity
      of drug activity at beta-ARs, prototypical G protein-coupled receptors,
      necessitates rethinking of the approaches used for screening and characterization
      of novel therapeutic agents. Most studies of ligand-directed signalling employ
      recombinant cell systems with high receptor abundance. While such systems are
      valid for examining upstream signalling events, such as receptor conformational
      changes and G protein activation, they are less robust when comparing downstream
      signalling outputs as these are likely to be affected by complex pathway
      interactions.

PMID- 20132210
TI  - Mechanisms involved in the antinociception induced by systemic administration of
      guanosine in mice.
AB  - BACKGROUND AND PURPOSE: It is well known that adenine-based purines exert
      multiple effects on pain transmission. However, less attention has been given to
      the potential effects of guanine-based purines on pain transmission. The aim of
      this study was to investigate the effects of intraperitoneal (i.p.) and oral
      (p.o.) administration of guanosine on mice pain models. Additionally,
      investigation into the mechanisms of action of guanosine, its potential toxicity
      and cerebrospinal fluid (CSF) purine levels were also assessed. EXPERIMENTAL
      APPROACH: Mice received an i.p. or p.o. administration of vehicle (0.1 mM NaOH)
      or guanosine (up to 240 mg x kg(-1)) and were evaluated in several pain models.
      KEY RESULTS: Guanosine produced dose-dependent antinociceptive effects in the hot
      plate, glutamate, capsaicin, formalin and acetic acid models, but it was
      ineffective in the tail-flick test. Additionally, guanosine produced a
      significant inhibition of biting behaviour induced by i.t. injection of
      glutamate, AMPA, kainate and trans-ACPD, but not against NMDA, substance P or
      capsaicin. The antinociceptive effects of guanosine were prevented by selective
      and non-selective adenosine receptor antagonists. Systemic administration of
      guanosine (120 mg x kg(-1)) induced an approximately sevenfold increase on CSF
      guanosine levels. Guanosine prevented the increase on spinal cord glutamate
      uptake induced by intraplantar capsaicin. CONCLUSIONS AND IMPLICATIONS: This
      study provides new evidence on the mechanism of action of the antinociceptive
      effects after systemic administration of guanosine. These effects seem to be
      related to the modulation of adenosine A(1) and A(2A) receptors and non-NMDA
      glutamate receptors.

PMID- 20132211
TI  - KMUP-1 attenuates isoprenaline-induced cardiac hypertrophy in rats through
      NO/cGMP/PKG and ERK1/2/calcineurin A pathways.
AB  - BACKGROUND AND PURPOSE: To determine whether KMUP-1, a novel xanthine-based
      derivative, attenuates isoprenaline (ISO)-induced cardiac hypertrophy in rats,
      and if so, whether the anti-hypertrophic effect is mediated by the nitric oxide
      (NO) pathway. EXPERIMENTAL APPROACH: In vivo, cardiac hypertrophy was induced by
      injection of ISO (5 mg.kg(-1).day(-1), s.c.) for 10 days in Wistar rats. In the
      treatment group, KMUP-1 was administered 1 h before ISO. After 10 days, effects
      of KMUP-1 on survival, cardiac hypertrophy and fibrosis, the NO/guanosine 3'5'
      cyclic monophosphate (cGMP)/protein kinase G (PKG) and hypertrophy signalling
      pathways [calcineurin A and extracellular signal-regulated kinase (ERK)1/2] were
      examined. To investigate the role of nitric oxide synthase (NOS) in the effects
      of KMUP-1, a NOS inhibitor, N(omega)-nitro-L-arginine (L-NNA) was co-administered
      with KMUP-1. In vitro, anti-hypertrophic effects of KMUP-1 were studied in ISO
      induced hypertrophic neonatal rat cardiomyocytes. KEY RESULTS: In vivo, KMUP-1
      pretreatment attenuated the cardiac hypertrophy and fibrosis and improved the
      survival of ISO-treated rats. Plasma NOx (nitrite and nitrate) and cardiac
      endothelial NOS, cGMP and PKG were all increased by KMUP-1. The activation of
      hypertrophic signalling by calcineurin A and ERK1/2 in ISO-treated rats was also
      attenuated by KMUP-1. All these effects of KMUP-1 were inhibited by simultaneous
      administration of L-NNA. Similarly, in vitro, KMUP-1 attenuated hypertrophic
      responses and signalling induced by ISO in neonatal rat cardiomyocytes.
      CONCLUSIONS AND IMPLICATIONS: KMUP-1 attenuates the cardiac hypertrophy in rats
      induced by administration of ISO. These effects are mediated, at least in part,
      by NOS activation. This novel agent, which targets the NO/cGMP pathway, has a
      potential role in the prevention of cardiac hypertrophy.

PMID- 20132213
TI  - Principles of pharmacoeconomics and their impact on strategic imperatives of
      pharmaceutical research and development.
AB  - The importance of evidence-based health policy is widely acknowledged among
      health care professionals, patients and politicians. Health care resources
      available for medical procedures, including pharmaceuticals, are limited all over
      the world. Economic evaluations help to alleviate the burden of scarce resources
      by improving the allocative efficiency of health care financing. Reimbursement of
      new medicines is subject to their cost-effectiveness and affordability in more
      and more countries. There are three major approaches to calculate the cost
      effectiveness of new pharmaceuticals. Economic analyses alongside pivotal
      clinical trials are often inconclusive due to the suboptimal collection of
      economic data and protocol-driven costs. The major limitation of observational
      naturalistic economic evaluations is the selection bias and that they can be
      conducted only after registration and reimbursement. Economic modelling is
      routinely used to predict the cost-effectiveness of new pharmaceuticals for
      reimbursement purposes. Accuracy of cost-effectiveness estimates depends on the
      quality of input variables; validity of surrogate end points; and appropriateness
      of modelling assumptions, including model structure, time horizon and
      sophistication of the model to differentiate clinically and economically
      meaningful outcomes. These economic evaluation methods are not mutually
      exclusive; in practice, economic analyses often combine data collection alongside
      clinical trials or observational studies with modelling. The need for
      pharmacoeconomic evidence has fundamentally changed the strategic imperatives of
      research and development (R&D). Therefore, professionals in pharmaceutical R&D
      have to be familiar with the principles of pharmacoeconomics, including the
      selection of health policy-relevant comparators, analytical techniques,
      measurement of health gain by quality-adjusted life-years and strategic pricing
      of pharmaceuticals.

PMID- 20132212
TI  - Open questions in current models of antidepressant action.
AB  - Research on depression and antidepressant drugs is necessary, as many patients
      display poor response to therapy. Different symptomatic and pathophysiological
      features have been proposed as end points of the depressive phenotype and of the
      antidepressant action, including anhedonia, depressed mood, alterations in
      morphology and activity of some brain areas (amygdala, nucleus accumbens,
      hippocampus, prefrontal cortex and cingulate cortex), modifications in the
      connectivity between brain structures, changes in neurotransmitters (serotonin,
      noradrenaline, glutamate and neuropeptides), brain plasticity (neurogenesis,
      neurotrophins) and abnormal function of the hypothalamic-pituitary adrenal axis.
      However, few models have been proposed to describe how these end points could
      induce the depressive phenotype and are involved in the mechanism of action of
      antidepressants. Here we propose a connectionist-inspired network of depression
      and antidepressant action, in which the different aetiological factors
      participating in the release of a depressive episode are represented by input
      nodes, the different symptomatic as well as pathophysiological end points are
      represented by an intermediate layer, and the onset of depression or of comorbid
      disease is represented by the output node. The occurrence of depression and the
      mechanism of the antidepressant action thus depend upon the weight of the
      interactions between the different end points, none of them being per se crucial
      to the onset of a depressive phenotype or to the antidepressant action. This
      model is heuristic to draw future lines of research concerning new antidepressant
      therapies, designing new animal models of depression and for a better
      understanding of the depressive pathology and of its comorbid pathology such as
      anxiety disorders.

PMID- 20132214
TI  - High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and
      progression in gastric cancer.
AB  - Gastric cancers show high frequency of DNA aneuploidy, a phenotype of chromosomal
      instability. It is suggested that the abnormal spindle assembly checkpoint is
      involved in DNA aneuploidy, but the underlying mechanism is still unclear. We
      studied the mechanism by assessing the expression of BUBR1 in gastric cancer. The
      DNA ploidy patterns of 116 gastric cancer samples obtained from the Department of
      Surgery and Science at Kyushu University Hospital were analyzed. Of those, DNA
      aneuploidy was seen in 70 (60.3%) cases of gastric cancer. The expression of
      BUBR1 was studied by immunohistochemistry in 181 gastric cancer samples and by
      real-time RT-PCR in several gastric cancer cell lines. Ninety-one (50.3%) cases
      had high expression of BUBR1 and those cases correlated significantly with DNA
      aneuploidy (P < 0.05). Also high expression of BUBR1 cases had significant
      correlation with deep invasion, lymph node metastasis, liver metastasis, and poor
      prognosis. In gastric cancer cell lines, high expression of BUBR1 had a
      significant relationship with DNA aneuploidy (P < 0.05). Then, gastric cancer
      cell lines MKN-28 and SNU-1 were transfected with full-length BUBR1 to observe
      the significance of the change in BUBR1 expression. Enforced expression of BUBR1
      resulted in changes to the ploidy pattern and high Ki-67 expression.
      Collectively, our clinical and in vitro data indicate that high expression of
      BUBR1 may be one of causative factors for the induction of DNA aneuploidy and
      progression of gastric cancer.

PMID- 20132215
TI  - Incidence and survival trends for childhood cancer in Osaka, Japan, 1973-2001.
AB  - Mortality for childhood cancer has declined in Osaka, as well as all over Japan,
      since the 1970s, but whether this decline can be explained by trends of incidence
      or survival of childhood cancer has not been examined. A total of 5960 malignant
      tumors diagnosed between 1973 and 2001 in children <15 years of age were
      registered at the Osaka Cancer Registry in Japan. The time trends for childhood
      cancer were analyzed over 29 years for incidence and 20 years for survival.
      Leukemia was the most common among childhood cancer for both sexes and accounted
      for one-third of all cases. The age-standardized annual incidence rate of all
      tumors was highest in 1988-1992: 155.1 per million for males and 135.9 for
      females. Five-year survival for all tumors improved from 50.1% in 1978-1982 to
      73.0% in 1993-1997 for males and from 52.3% to 76.3% for females. Thus, the
      constant decline in mortality in childhood cancer was primarily due to improved
      survival between the 1970s and 1980s and reduced incidence after the 1990s.

PMID- 20132216
TI  - Dominant-negative derivative of EBNA1 represses EBNA1-mediated transforming gene
      expression during the acute phase of Epstein-Barr virus infection independent of
      rapid loss of viral genome.
AB  - The oncogenic human herpes virus, the Epstein-Barr virus (EBV), expresses EBNA1
      in almost all forms of viral latency. EBNA1 plays a major role in the maintenance
      of the viral genome and in the transactivation of viral transforming genes,
      including EBNA2 and latent membrane protein (LMP-1). However, it is unknown
      whether inhibition of EBNA1 from the onset of EBV infection disrupts the
      establishment of EBV's latency and transactivation of the viral oncogenes. To
      address this, we measured EBV infection kinetics in the B cell lines BALL-1 and
      BJAB, which stably express a dominant-negative EBNA1 (dnE1) fused to green
      fluorescent protein (GFP). The EBV genome was surprisingly unstable 1 week post
      infection: the average loss rate of EBV DNA from GFP- and GFP-dnE1-expressing
      cells was 53.4% and 41.0% per cell generation, respectively, which was
      substantially higher than that of an 'established'oriP replicon (2-4%). GFP-dnE1
      did not accelerate loss of the EBV genome, suggesting that EBNA1-dependent
      licensing of the EBV genome occurs infrequently during the acute phase of EBV
      infection. In the subacute phase, establishment of EBV latency was completely
      blocked in GFP-dnE1-expressing cells. In contrast, C/W promoter-driven
      transcription was strongly restricted in GFP-dnE1-expressing cells at 2 days post
      infection. These data suggest that inhibition of EBNA1 from the onset of EBV
      infection is effective in blocking the positive feedback loop in the
      transactivation of viral transforming genes, and in eradicating the EBV genome
      during the subacute phase. Our results suggest that gene transduction of GFP-dnE1
      could be a promising therapeutic and prophylactic approach toward EBV-associated
      malignancies.

PMID- 20132219
TI  - Girding for migratory cues: roles of the Akt substrate Girdin in cancer
      progression and angiogenesis.
AB  - Cell migration is a fundamental aspect of a multitude of physiological and
      pathological processes, including embryonic development, inflammation,
      angiogenesis, and cancer progression. A variety of proteins are essential for
      cell migration, but context-specific signaling pathways and promigratory proteins
      must now be identified for our understanding of cancer biology to continue to
      advance. In this review, we focus on the emerging roles of Girdin (also
      designated KIAA1212, APE, GIV, and HkRP1), a novel component of the
      phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway that is a core
      signaling transduction pathway in cancer progression. Girdin is expressed in some
      types of cancer cells and immature endothelial cells, and is therefore at the
      crossroads of multiple intracellular processes, including reorganization of the
      actin cytoskeleton, endocytosis, and modulation of Akt activity, which ultimately
      lead to cancer invasion and angiogenesis. It also acts as a nonreceptor guanine
      nucleotide exchange factor (GEF) for Galphai proteins. A significant observation
      is that Girdin, although vital for cancer progression and postnatal vascular
      remodelling, is dispensable for cell migratory events during embryonic
      development. These findings suggest that Girdin and its interacting proteins are
      potential pharmaceutical targets for cancer therapies and pathological
      anigiogenesis, including tumor angiogenesis.

PMID- 20132220
TI  - Biased usage of BV gene families of T-cell receptors of WT1 (Wilms' tumor gene)
      specific CD8+ T cells in patients with myeloid malignancies.
AB  - WT1 (Wilms' tumor gene 1) protein is a potent pan-tumor-associated antigen (TAA)
      and WT1-specific cytotoxic T lymphocytes (WT1 tetramer(+) CD8(+) T cells) are
      spontaneously induced in patients with acute myeloid leukemia (AML) or
      myelodysplastic syndrome (MDS). We conducted a single-cell level comparative
      analysis of T-cell receptor beta-chain variable region (TCR-BV) gene families of
      a total of 1242 spontaneously induced WT1 tetramer(+) CD8(+) T cells in HLA
      A*2402(+) patients with AML or MDS and those in healthy donors (HDs). This is the
      first report of direct usage analysis of TCR-BV gene families of individual TAA
      specific CD8(+) T cells at single-cell level. Usage analysis using single-cell RT
      PCR of TCR-BV gene families of individual FACS-sorted WT1 tetramer(+) CD8(+) T
      cells showed for the first time (i) that BVs 5, 6, 20, and 27 were commonly
      biased in both HDs and patients; (ii) that BV4 was commonly biased in HDs and MDS
      patients; (iii) that BV19 was commonly biased in the patients; and (iv) that BVs
      7 and 28, BVs 9 and 15, and BVs 12 and 29 were specifically biased in HDs, AML,
      and MDS patients, respectively. However, statistical analysis of similarity among
      HD, AML, and MDS of individual usage frequencies of 24 kinds of TCR-BV gene
      families indicated that the usage frequencies of TCR-BV gene families in AML and
      MDS patients reflect those in HDs. These findings represent a novel insight for a
      better understanding of WT1-specific immune response.

PMID- 20132221
TI  - Age dependence of radiation-induced renal cell carcinomas in an Eker rat model.
AB  - Exposure to carcinogens early in life may contribute to cancer development later
      in life. The amount of radiation exposure children experience during medical
      procedures has been increasing, so it is important to evaluate the radiation risk
      of cancer in developing organs. Toward this goal, we assessed the risk of
      developing renal cell carcinoma using Eker rats as a kidney tumor model. F1
      hybrids of male Eker (Tsc2 mutant) and female F344 rats were irradiated with 0.5
      or 2 Gy gamma radiation on gestation days 15 and 19, and on postnatal days 5, 20,
      and 49. At 27 weeks of age, kidneys were examined for proliferative lesions.
      Preneoplastic lesions such as phenotypically altered tubules increased after
      postnatal irradiation as a function of age-at-irradiation, and hyperplasia were
      greatly increased after perinatal and postnatal irradiation. In contrast,
      development of adenoma and adenocarcinoma were evident in animals irradiated at
      perinatal ages, being maximal at gestational day 19. The frequency of LOH at the
      Tsc2 locus was unexpectedly low - 0% (0 of 4) for the unirradiated control, and
      17% (6 of 35) for the irradiated group. Irrespective of LOH, the mTOR (mammalian
      target of rapamycin) pathway, which is negatively regulated by the Tsc1/2
      complex, was activated in both benign and malignant lesions, as evidenced by
      phosphorylation of S6 ribosomal protein and 4E-BP1. This suggests that the wild
      type Tsc2 allele may be functionally inactivated. In conclusion, actively growing
      kidneys in perinatal-aged (F344 x Eker) F1 rats (Tsc2(+/-)) are at risk for
      radiation-induced malignant transformation of the renal epithelium associated
      with mTOR activation.

PMID- 20132222
TI  - Recurrence and mortality dynamics for breast cancer patients undergoing
      mastectomy according to estrogen receptor status: different mortality but similar
      recurrence.
AB  - (Cancer Sci 2010; 101: 826-830) The purpose was to ascertain whether the
      recurrence risk patterns for patients with estrogen receptor (ER)-positive (P)
      and ER-negative (N) breast cancer support the ER-related clinical divergence
      suggested by the observed different mortality patterns and gene expression
      profiles. Both recurrence and death were considered in a series of 771 patients
      undergoing mastectomy. ER status was available for 539 patients. The hazard rates
      for recurrence and mortality throughout 15 years of follow-up were assessed. The
      recurrence dynamics displays a bimodal pattern for both ERP and ERN tumors with
      comparable peak timings. The two curves cross during the 3rd year. By contrast,
      the mortality dynamics are definitely different for ERP and ERN tumors: during
      the early follow-up period ERN patients have their highest mortality risk, while
      ERP patients have their lowest mortality risk. The two curves cross during the
      5th year. In spite of the different mortality dynamics, the recurrence dynamics
      do not demonstrate a major distinction in timing between ERP and ERN breast
      cancers, suggesting that the metastasis development process following mastectomy
      is apparently similar for both ER categories. The observed differences in the
      mortality risk are plausibly attributable to ER-related factors influencing the
      clinical course from recurrence to death. These clinical findings apparently
      contradict the occurrence of two different types of breast cancer,
      notwithstanding the distinct epidemiological, clinical, and molecular features
      linked to ERP and ERN tumors, although ER levels may concur to establish the
      event risk levels.

PMID- 20132223
TI  - Histone acetylation and steroid receptor coactivator expression during clofibrate
      induced rat hepatocarcinogenesis.
AB  - Peroxisome proliferators (PPs), non-genotoxic rodent carcinogens, cause the
      induction of the peroxisomal fatty acid beta-oxidation system, including
      bifunctional enzyme (BE) and 3-ketoacyl-CoA thiolase (TH), in the liver. GST M1
      gene is polymorphic in Sprague-Dawley rats, NC- and KS-type. The KS-type rats
      showed enhanced susceptibility to ethyl-alpha-chlorophenoxyisobutyrate
      (clofibrate, CF), one of the PPs. The degree of BE induction was higher in the KS
      type and preneoplastic foci developed after 6-8 weeks of treatment, whereas no
      foci developed in the NC-type. In the preset study, factors involved in different
      BE inducibility were investigated. There were no differences in hepatic
      peroxisome proliferator-activated receptor (PPAR) alpha levels between them.
      Among various coactivators for PPARalpha, only steroid receptor coactivator (SRC)
      3 level was higher in the KS-type. To investigate the association between
      PPARalpha and SRC-3 or other proteins, nuclear extracts from CF-treated livers
      were applied to a PPARalpha column. In the KS-type, 110, 72, and 42 kDa proteins
      were bound and these were identified as SRC-3, BE, and TH, respectively. EMSA
      supported the binding of these proteins to PPARalpha associated to the BE
      enhancer in CF-treated KS-type, but not in the NC-type. Histone H3 acetylation
      was increased 11-fold in the KS-type by CF treatment but not in the NC-type. As
      BE and TH are responsible for acetyl-CoA production and SRC-3 possesses a histone
      acetyltransferase activity, these results suggest that enhanced BE induction in
      the KS-type livers is due to acetylation-mediated transcriptional activation and
      epigenetic mechanisms might be involved in CF-induced rat hepatocarcinogenesis.

PMID- 20132225
TI  - The cell death machinery governed by the p53 tumor suppressor in response to DNA
      damage.
AB  - The cellular response to genotoxic stress that damages DNA includes cell cycle
      arrest, activation of DNA repair, and in the event of irreparable damage,
      induction of apoptosis. However, the signals that determine cell fate, that is,
      survival or apoptosis, are largely unclear. The tumor suppressor p53 has been
      implicated in many important cellular processes, including regulation of
      apoptotic cell death. When cells encounter genotoxic stress, certain sensors for
      DNA lesions eventually stabilize and activate p53. Subsequently, p53 exerts its
      tumor suppressor function by transactivating numerous target genes. Active p53 is
      subjected to a complex and diverse array of covalent post-translational
      modifications, which selectively influence the expression of p53 target genes. In
      this regard, the molecular basis for how p53 induces apoptosis has been
      extensively studied; however, the relative contribution of each downstream
      effector is still to be explored. Moreover, little is known about precise
      mechanisms by which modified p53 is capable of apoptosis induction. A thorough
      understanding for the whole picture of p53 modification in apoptosis will be
      extremely valuable in the development of highly effective and specific therapies
      for cancer patients. This review is focused on the current views regarding the
      regulation of cell fate by p53 in the apoptotic response to DNA damage.

PMID- 20132229
TI  - Infant CD4 C868T polymorphism is associated with increased human immunodeficiency
      virus (HIV-1) acquisition.
AB  - The C868T single nucleotide polymorphism (SNP) in the CD4 receptor encodes an
      amino acid change that could alter its structure and influence human
      immunodeficiency virus (HIV-1) infection risk. HIV-1-infected pregnant women in
      Nairobi were followed with their infants for 1 year postpartum. Among 131
      infants, those with the 868T allele were more likely than wild-type infants to
      acquire HIV-1 overall [hazard ratio (HR) = 1.92, 95% confidence interval (CI)
      1.05, 3.50, P = 0.03; adjusted HR = 2.03, 95% CI 1.03, 3.98, P = 0.04], after
      adjusting for maternal viral load. This SNP (an allele frequency of approximately
      15% in our cohort) was associated with increased susceptibility to mother-to
      child HIV-1 transmission, consistent with a previous study on this polymorphism
      among Nairobi sex workers.

PMID- 20132230
TI  - Interleukin-2 inhibits polarization to T helper type 1 cells and prevents mouse
      acute graft-versus-host disease through up-regulating suppressors of cytokine
      signalling-3 expression of naive CD4+ T cells.
AB  - T helper type 1 (Th1)-type polarization plays a critical role in the
      pathophysiology of acute graft-versus-host disease (aGVHD). The differentiation
      of T cells into this subtype is dictated by the nature of the donor naive CD4(+)
      T cell-host antigen presenting cell (APC) interaction. Suppressors of cytokine
      signalling (SOCS) are a family of molecules that act as negative regulators for
      cytokine signalling, which regulate the negative cytokine signalling pathway
      through inhibiting the cytokine-induced Janus kinase/signal transducer and
      activator of transcription (JAK/STAT) pathway. Studies have shown that SOCS
      proteins are key physiological regulators of both innate and adaptive immunity.
      These molecules are essential for T cell development and differentiation. SOCS-3
      can inhibit polarization to Th1 and contribute to polarization to Th2. In this
      study, we found that interleukin (IL)-2 pre-incubation of C57BL/6 naive CD4(+) T
      cells could up-regulate the expression of SOCS-3. Naive CD4(+) T cells
      constitutively expressed low levels of SOCS-3 mRNA. SOCS-3 mRNA began to rise
      after 4 h, and reached peak level at 6 h. At 8 h it began to decrease. High
      expression of SOCS-3 mRNA induced by IL-2 could inhibit the proliferation of
      naive CD4(+) T cells following stimulation with allogeneic antigen. IL-2-induced
      high SOCS-3 expression in naive CD4(+) T cells could inhibit polarization to Th1
      with stimulation of allogeneic antigens. We have demonstrated that IL-2-induced
      high SOCS-3 expression in naive CD4(+) T cells could reduce the incidence of
      aGVHD between major histocompatibility complex (MHC) completely mismatched donor
      and host when high SOCS3 expression of CD4(+)T cells encounter allogeneic antigen
      in time. These results show that IL-2-induced high SOCS-3 expression can inhibit
      aGVHD through inhibiting proliferation and polarization to Th1 with the
      stimulation of allogeneic antigen.

PMID- 20132231
TI  - Schistosoma mansoni antigens modulate the allergic response in a murine model of
      ovalbumin-induced airway inflammation.
AB  - Schistosoma mansoni infection has been associated with protection against
      allergies. The mechanisms underlying this association may involve regulatory
      cells and cytokines. We evaluated the immune response induced by the S. mansoni
      antigens Sm22.6, PIII and Sm29 in a murine model of ovalbumin (OVA)-induced
      airway inflammation. BALB/c mice were sensitized with subcutaneously injected OVA
      alum and challenged with aerolized OVA. Mice were given three doses of the
      different S. mansoni antigens. Lung histopathology, cellularity of
      bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in lung were
      evaluated. Immunoglobulin (Ig)E levels in serum and cytokines in BAL were also
      measured. Additionally, we evaluated the frequency of CD4+forkhead box P3
      (FoxP3)+ T cells in cultures stimulated with OVA and the expression of
      interleukin (IL)-10 by these cells. The number of total cells and eosinophils in
      BAL and the levels of OVA-specific IgE were reduced in the immunized mice. Also,
      the levels of IL-4 and IL-5 in the BAL of mice immunized with PIII and Sm22.6
      were decreased, while the levels of IL-10 were higher in mice immunized with
      Sm22.6 compared to the non-immunized mice. The frequency of CD4+FoxP3+ T cells
      was higher in the groups of mice who received Sm22.6, Sm29 and PIII, being the
      expression of IL-10 by these cells only higher in mice immunized with Sm22.6. We
      concluded that the S. mansoni antigens used in this study are able to down
      modulate allergic inflammatory mediators in a murine model of airway inflammation
      and that the CD4+FoxP3+ T cells, even in the absence of IL-10 expression, might
      play an important role in this process.

PMID- 20132232
TI  - Performance of 'energy efficient' compact fluorescent lamps.
AB  - BACKGROUND: Compact fluorescent lamps (CFLs) have been heralded as highly energy
      efficient replacements for incandescent light globes, however, there is some
      public dissatisfaction with the light output and colour of CFLs. Independent
      examination of the claims made has not been made. Compliance with the interim
      Australian/New Zealand Standard has not been established by any independent
      authority. While the total light output (luminous flux) may meet certain
      standards, luminous intensity distributions of some designs do differ
      significantly from the incandescent sources that they are intended to replace.
      METHODS: Luminous intensity distribution, luminous flux and spectral energy
      distribution of CFLs claimed to be equivalent to 75 W incandescent globes and 75
      W incandescent globes (pearl and clear) were measured. Luminous flux, luminous
      efficacy, colour rendering index, correlated colour temperature, wattage and
      power factor were then calculated and compared with claims made by manufacturers
      and requirements of the standards. RESULTS: The sources generally complied with
      the requirements for luminous flux, luminous efficacy, colour rendering index and
      correlated colour temperature. The claim of 75 W equivalence, which is not
      regulated in Australia and New Zealand, is justified less than half the time.
      Luminous intensity distributions of biaxial CFLs are distinctly different from
      the incandescent lamps they purport to replace. CONCLUSION: CFLs generally comply
      with the standards set. The basis on which equivalent wattages are claimed needs
      to be included in the Australian and New Zealand standard because this is the
      measure most likely to be relied on by the public. Due to the differences in
      luminous intensity distribution, CFLs may not necessarily be a direct replacement
      for incandescent sources without some consideration.

PMID- 20132233
TI  - Erythropoietin inhibits gamma-irradiation-induced apoptosis by upregulation of
      Bcl-2 and decreasing the activation of caspase 3 in human UT-7/erythropoietin
      cell line.
AB  - 1. Erythropoietin (EPO) can reverse radiotherapy-induced anaemia by stimulating
      bone marrow cells to produce erythrocytes. However, there are limited studies
      that address the mechanisms by which EPO exerts its beneficial effects in
      radiotherapy-induced anaemia. In the present study, we used a human bone marrow
      derived EPO-dependent leukaemia cell line UT-7/EPO that progressed further in
      erythroid development to evaluate the anti-apoptotic effects of EPO on irradiated
      human erythroid progenitor. 2. The UT-7/EPO cells exposed to gamma-irradiation
      were cultured in the presence or absence of EPO at a concentration of 7 U/mL. The
      cell viability, cell apoptosis and the expression of apoptosis-related proteins
      Bcl-2, Bax and caspase 3 were examined. 3. The results showed that EPO protected
      the viability of human UT-7/EPO cells exposed to gamma-irradiation. EPO
      significantly inhibited gamma-irradiation-induced apoptosis in human UT-7/EPO
      cells: a significant decrease in the percentage of apoptotic cells was observed
      (62, 69 and 62% at 24, 48 and 72 h, respectively). Furthermore, EPO significantly
      increased the expression of Bcl-2 protein and the relative Bcl-2/Bax ratio, and
      decreased the activation of caspase 3 and formation of the p17 and p12 cleavage
      in similar conditions. 4. In conclusion, EPO exerts anti-apoptotic effects on
      irradiated human UT-7/EPO cells through upregulation of Bcl-2 protein and the
      relative Bcl-2/Bax ratio, and by decreasing the activation of caspase 3. These
      findings may contribute to our understanding of the beneficial function of EPO in
      radiotherapy-induced anaemia.

PMID- 20132234
TI  - Effects of flecainide and quinidine on action potential and ventricular
      arrhythmogenic properties in Scn3b knockout mice.
AB  - 1. Flecainide and quinidine exert contrasting pro-arrhythmic and anti-arrhythmic
      effects in mouse hearts containing the loss-of-function, Scn5a(+/-), and the gain
      of-function, Scn5a(+/DeltaKPQ), mutations in their sodium channel alpha-subunits.
      2. The following properties were accordingly compared in wild-type and Scn3b(-/-)
      hearts modelling modifications in the beta-subunit, before and after introduction
      of either agent: (i) ventricular arrhythmogenecity and effective refractory
      periods (VERP) in response to programmed electrical stimulation (PES); (ii)
      monophasic action potential waveforms recorded from the left ventricular
      epicardium and endocardium; (iii) action potential durations (APD) obtained from
      the monophasic action potentials; and (iv) critical intervals derived from the
      APD and VERP values. 3. Ventricular tachycardia was induced by PES in 11 out of
      15 Scn3b(-/-) hearts and 0 out of 17 wild-type hearts. This incidence was reduced
      to three out of eight Scn3b(-/-) hearts but increased to three out of eight wild
      type hearts with flecainide. 4. Arrhythmogenic incidence was reduced to two out
      of eight Scn3b(-/-) hearts and remained at 0 out of eight wild-type hearts in the
      presence of quinidine. 5. Ventricular effective refractory periods were prolonged
      and endocardial and epicardial APD shortened, resulting in negative critical
      intervals in both Scn3b(-/-) and wild-type hearts treated by either flecainide or
      quinidine. Nevertheless, endocardial APD remained consistently longer than
      epicardial APD, leaving similar, positive endocardial-epicardial, differences,
      DeltaAPD, in treated and untreated Scn3b(-/-) and wild-type hearts. 6. It is
      concluded that both flecainide and quinidine exert anti-arrhythmogenic effects in
      Scn3b(-/-) hearts, doing so through modifying VERP rather than DeltaAPD, in
      contrast to their differing effects in Scn5a(+/-) and Scn5a(+/DeltaKPQ) hearts.

PMID- 20132235
TI  - Inhibitory effect of resveratrol derivative BTM-0512 on high glucose-induced cell
      senescence involves dimethylaminohydrolase/asymmetric dimethylarginine pathway.
AB  - 1. It has been reported that resveratrol exerts the inhibitory effects on aging
      through activation of sirtuin 1 (SIRT1) and dimethylarginine
      dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway involved
      in the high glucose-induced endothelial cell senescence. 2. The aims of this work
      were to explore whether BTM-0512, a novel derivative of resveratrol, was able to
      exert the beneficial effect on high glucose-induced cellular senescence through
      regulating the DDAH/ADMA pathway and to explore whether the regulatory effect of
      BTM-0512 on DDAH/ADMA pathway was related to the activation of SIRT1. 3. The
      senescence model of endothelial cells was induced by high glucose and the cells
      were collected for the determination of beta-galactosidase and DDAH activity,
      ADMA level, DDAH and SIRT1 mRNA expression. 4. The results showed that high
      glucose significantly increased the ratio of senescent cells concomitantly with
      the decreased DDAH activity, the downregulated DDAH2 and SIRT1 mRNA expressions
      and the increased ADMA levels, which were attenuated by pretreatment with BTM
      0512. 5. The beneficial effects of BTM-0512 on high glucose-induced senescence
      were blocked by splimtomicin, the specific inhibitor of SIRT1, or by silencing
      DDAH2 expression. 6. The results suggest that BTM-0512 was able to exert the
      beneficial effects on high glucose-induced cellular senescence through regulating
      the DDAH/ADMA pathway, and its regulatory effect on DDAH/ADMA pathway was related
      to the activation of SIRT1.

PMID- 20132236
TI  - Tranilast stabilizes the accumulation and degranulation of resident mast cells
      while reducing cardiomyocyte apoptosis in a swine model of coronary
      microembolisation.
AB  - 1. Coronary microembolisation (CME) is associated with progressive myocardial
      dysfunction, and mast cells (MC) might have an important role in myocardial
      apoptosis after CME. We investigated whether the MC stabilizer tranilast
      suppresses the accumulation and degranulation of MC while reducing cardiomyocyte
      apoptosis after CME. 2. We induced CME in miniswine by selective infusion of 15 x
      10(4) microspheres (diameter 45 microm) into the left anterior descending artery.
      Some CME-induced miniswine were treated with the MC stabilizer tranilast (50
      mg/kg, p.o., b.d.) beginning 2 weeks before CME, and thereafter throughout the
      experimental period; others received tranilast without CME; and sham-operated
      animals without CME served as controls. After 30 days, we assessed cardiomyocyte
      apoptosis by TUNEL assay and by the total number of MC and the number of
      degranulating MC using histology and transmission electron microscopy. The wall
      motion score index and left ventricular ejection fraction were studied by
      dobutamine stress echocardiography. 3. Coronary microembolisation was associated
      with increases in the total number of MC, the number of degranulating MC, and
      myocyte apoptosis. The number of total MC and degranulating MC and apoptotic
      cardiomyocytes over the anterior embolized myocardium after CME were
      significantly higher than those over the posterior control myocardium and
      anterior segments per animal without CME (P < 0.01). Tranilast administration to
      CME miniswine suppressed cardiomyocyte apoptosis while maintaining regional and
      global function, which was associated with reductions in the accumulation and
      degranulation of MC. 4. These findings suggest that tranilast suppresses the
      accumulation and degranulation of MC while reducing cardiomyocyte apoptosis after
      CME.

PMID- 20132237
TI  - Effects of nicorandil on sympathetic neurotransmission in rat caudal artery.
AB  - 1. We examined the effects of nicorandil, an ATP-sensitive potassium (K(ATP))
      channel opener and nitric oxide donor, on the release of noradrenaline from
      vascular sympathetic nerves. This effect was compared to the effect on vascular
      smooth muscle. 2. Caudal artery preparations from Wistar rats were electrically
      stimulated (1 Hz, 0.5-ms duration) and noradrenaline release in the artery was
      detected using an high-pressure liquid chromatography-electrochemical detection
      technique. The pharmacological properties of the prejunctional effect of
      nicorandil were determined using the nonselective K(ATP) channel blocker
      glibenclamide, the pancreatic beta-cell and brain-type K(ATP) channel blocker
      tolbutamide, and the smooth muscle-type K(ATP) channel blocker PNU-37883A. 3.
      Nicorandil inhibited the electrical stimulation-evoked noradrenaline release in a
      concentration-dependent manner. This inhibitory effect was abolished by 1
      micromol/L glibenclamide and 10 micromol/L tolbutamide, but was not affected by
      10 micromol/L PNU-37883A or 0.3 micromol/L ODQ. Nicorandil did not affect the
      noradrenaline transporter uptake 1 in the adrenergic nerve terminals. 4.
      Nicorandil produced a relaxation response in a concentration-dependent manner in
      the caudal artery pre-contracted with 0.3 micromol/L noradrenaline. This
      relaxation response was significantly diminished in the presence of 1 micromol/L
      glibenclamide, 10 micromol/L PNU-37883A and 0.3 micromol/L ODQ but not by 10
      micromol/L tolbutamide. 5. These findings suggest that nicorandil inhibits
      noradrenaline release via the K(ATP) channels of sympathetic nerves. These
      channels may be pharmacologically different from those of vascular smooth muscle.

PMID- 20132238
TI  - Tumour-selective antivascular effects of the novel anti-mitotic compound A
      318315: An in vivo rat regional haemodynamic study.
AB  - 1. It has been shown that tubulin-binding agents can destabilize cellular
      microtubules and suppress tumour growth; but it has also become apparent that
      some compounds can exert anti-vascular effects within the neovasculature of a
      solid tumour. To date, the difficulty with these targets has been the ability to
      selectivity induce vascular damage to the tumour while leaving normal vasculature
      unaffected. The data presented here characterizes the in vivo, tumour selective,
      anti-vascular effects of the novel tubulin-binding agent A-318315. 2. To that
      purpose, we have used an anaesthetized in vivo rat model designed to quantify
      acute changes in regional vascular resistance (VR) in both tumour and non-tumour
      vascular beds, simultaneously. Tissue-isolated tumours (approximately 1.25 gm)
      with blood flow supplied by a single epigastric artery were grown in the hindlimb
      of adult male rats. Blood flow to the tumour, mesenteric, renal and normal (non
      tumour epigastric) arteries was measured pre-dose and post-dose under
      anaesthesia. 3. A-318315 was tested at 3, 10 and 30 mg/kg, i.v. These doses
      produced modest, transient increases in mean arterial pressure with little to no
      effect on heart rate. At peak effect, tumour VR increased to 175 +/- 47, 337 +/-
      77 and 751 +/- 151% above the baseline, for the 3, 10 and 30 mg/kg doses,
      respectively, whereas VR was only modestly and transiently increased in normal
      epigastric (88 +/- 19%), mesenteric (33 +/- 3.3%) and renal arteries (17 +/-
      8.6%). 4. These data demonstrate that A-318315 produces marked reductions in
      tumour blood flow in the rat at doses that exert minor effects on normal vascular
      function.

PMID- 20132239
TI  - Dopamine-mediated inhibition of renal Na+/K+-ATPase in HK-2 cells is reduced by
      ouabain.
AB  - 1. Abnormal renal sodium handling is considered a major contributing factor in
      hypertension associated with chronic ouabain treatment. However, the molecular
      mechanisms involved in abnormal renal sodium handling have not been elucidated.
      Therefore, we investigated whether chronic ouabain treatment perturbs dopamine
      D(1) receptor function. 2. The expression and phosphorylation levels of the D(1)
      receptor in cells of the human proximal tubule cell line (HK-2) were determined
      using western blot analysis and reverse transcription polymerase chain reaction.
      The activity of the renal sodium/potassium pump (Na(+)/K(+)-ATPase) was measured
      using a colourimetric assay, and cyclic adenosine monophosphate accumulation was
      determined by performing a radioimmunoassay. 3. We showed that chronic ouabain
      treatment decreased the protein and mRNA expression levels of the D(1) receptor
      and increased the basal phosphorylation of the D(1) receptor in HK-2 cells. We
      also showed that in the presence of ouabain, HK-2 cells did not reveal the cyclic
      adenosine monophosphate accumulation and Na(+)/K(+)-ATPase inhibition induced by
      the D(1) receptor agonist fenoldopam. 4. We hypothesize that the ouabain-induced
      decrease in renal D(1) receptor function is responsible for the increase in renal
      sodium reabsorption, which eventually leads to ouabain-induced hypertension.

PMID- 20132240
TI  - Clinical and molecular aspects of aniridia.
AB  - Aniridia is a severe, congenital ocular malformation inherited in an autosomal
      dominant fashion with high penetrance and variable expression. Eye morphogenesis
      in humans involves a molecular genetic cascade in which a number of developmental
      genes interact in a highly organized process during the embryonic period to
      produce functional ocular structures. Among these genes, paired box gene 6 (PAX6)
      has an essential role as it encodes a phylogenetically conserved transcription
      factor almost universally employed for eye formation in animals with bilateral
      symmetry, despite widely different embryological origins. To direct eye
      development, PAX6 regulates the tissue-specific expression of diverse molecules,
      hormones, and structural proteins. In humans, PAX6 is located in chromosome
      11p13, and its mutations lead to a variety of hereditary ocular malformations of
      the anterior and posterior segment, among which aniridia and most probably foveal
      hypoplasia are the major signs. Aniridia occurs due to decreased dosage of the
      PAX6 gene and exists in both sporadic and familial forms. The mutations are
      scattered throughout the gene and the vast majority of those reported so far are
      nonsense mutations, frameshift mutations, or splicing errors that are predicted
      to cause pre-mature truncation of the PAX6 protein, causing haploinsufficiency.
      Here we review the data regarding the mechanisms and the mutations that relate to
      aniridia.

PMID- 20132241
TI  - microRNAs in diseases: from candidate to modifier genes.
AB  - Until recently, the search for genetic factors predisposing or causing Mendelian
      diseases focused almost exclusively on protein coding sequences. As essential
      components of the regulatory system of gene expression, microRNAs (miRNAs) hold
      great promises into elucidating a number of inherited diseases. The herein review
      focuses on the genetic variations, whether copy number variation (CNV) or single
      nucleotide polymorphism (SNP), alternatively at the levels of the miRNA gene
      itself and of its target genes. We consider miRNA as the candidate gene, or the
      regulator of a disease-causing gene, or the modifier gene. The best paradigms of
      the field are presented in both monogenic diseases and complex traits. The
      computational tools, which are essential into identifying miRNAs and
      characterizing miRNA targets, are overviewed.

PMID- 20132242
TI  - Variable hearing impairment in a DFNB2 family with a novel MYO7A missense
      mutation.
AB  - Myosin VIIA mutations have been associated with non-syndromic hearing loss
      (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and
      genetic analyses of a consanguineous Iranian family segregating autosomal
      recessive non-syndromic hearing loss (ARNSHL). The hearing impairment was mapped
      to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A
      gene was completed. The Iranian family (L-1419) was shown to segregate a novel
      homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid
      substitution in the motor domain of the myosin VIIA protein. As one affected
      family member had significantly less severe hearing loss, we used a candidate
      approach to search for a genetic modifier. This novel MYO7A mutation is the first
      reported to cause DFNB2 in the Iranian population and this DFNB2 family is the
      first to be associated with a potential modifier. The absence of vestibular and
      retinal defects, and less severe low frequency hearing loss, is consistent with
      the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude
      this family has non-syndromic hearing loss (DFNB2) rather than USH1B, providing
      further evidence that these two diseases represent discrete disorders.

PMID- 20132243
TI  - Novel exon nucleotide substitution at the splice junction causes a neonatal
      Marfan syndrome.
AB  - The fibrillin-1 gene (FBN1) mutations are associated with a broad spectrum of
      disorders including Marfan syndrome (MFS) and show great clinical heterogeneity.
      An underrepresentation for mutations leading to premature termination codon (PTC)
      in FBN1 exons 24-32 was found in neonatal or severe MFS but the underlying cause
      was unclear. This study thoroughly examined two FBN1 mutations on exons 24-32
      region to illustrate the molecular mechanisms underlying these FBN1 mutations on
      MFS etiology. Two nucleotide substitutions, c.3208G> C, the last nucleotide of
      exon 26, and c.3209A>G, the first nucleotide of exon 27, affecting the same amino
      acid, p.D1070H and p.D1070G, respectively, gave very different phenotypes. We
      demonstrate that c.3208G>C generates two alternatively spliced transcripts, while
      c.3209A>G does not affect the splicing. We further demonstrate that the
      aberrantly spliced transcripts do not go through nonsense-mediated decay, but
      rather produce unstable, premature protein peptides that are degraded by
      endoplasmic reticulum associated degradation. The molecular mechanism outlined
      here defines a model for the pathogenesis of PTC-containing mutation within the
      exons 24-32 of FBN1 in MFS. Furthermore, our data suggest that PTC mutation
      within this region may lead to early lethality in neonatal MFS.

PMID- 20132244
TI  - Novel and recurrent p14 mutations in Italian familial melanoma.
AB  - CDKN2A and CDK4 are the only known high-penetrant genes conferring proneness to
      cutaneous melanoma. The CDKN2A locus consists of four exons and encodes several
      alternate transcripts, two of which are p16(INK4a) and p14(ARF), and originate
      from different open reading frames. Exon 1alpha is specific for p16(INK4a), while
      exon 1beta characterizes p14(ARF). Most CDKN2A mutations are located in exons
      1alpha and 2, while exon 1beta variations have been identified in rare melanoma
      prone pedigrees. In a previous study, we investigated 155 Italian melanoma cases,
      including 94 familial melanomas (FAMs) and 61 sporadic multiple primary melanomas
      (MPMs), for p16(INK4a)/CDK4 germline alterations and identified 15 p16(INK4a) and
      1 CDK4 point mutations. In the present work, we extended our search to p14(ARF)
      mutations and CDKN2A deletions in the remaining samples. We identified the
      recurrent g.193+1G> A mutation in two FAM cases, while an additional pedigree
      displayed the previously undescribed variant g.161G> A. Multiplex ligation
      dependent probe amplification (MLPA) screening for copy variations resulted
      negative in all cases. In Italy, the overall frequency of p14(ARF) mutations is
      3.2% in FAM and 0% in sporadic MPM. Re-evaluation of our patients' cohort
      emphasizes that the chance of identifying CDKN2A/CDK4 mutations in FAM is mainly
      influenced by the number of affected family members and the presence of one or
      more MPM cases. Accordingly, mutation rate rises to 61% in selected cases.
      Further studies are expected in order to investigate CDKN2A rarer mutations,
      including atypical deletions and inherited epimutations.

PMID- 20132245
TI  - Preoperative diagnostic for palatal implants: Is CT or CBCT necessary?
AB  - OBJECTIVE: To evaluate (a) the diagnostic value of lateral radiographs and (b)
      whether computed tomography (CT) or cone beam computed tomography (CBCT) is
      necessary in preoperative diagnostics for orthodontic anchorage implants.
      PATIENTS AND METHODS: We reviewed all patients who had presented for insertion of
      a palatal implant between January 2003 and December 2007 at the University
      Hospital Mainz. On the basis of lateral radiographs, the palatal bone was
      assessed as follows: (a) sufficient (bone height > 4 mm in the implant axis), (b)
      ambiguous, or (c) insufficient (bone height < 4 mm in the implant axis). In group
      A the surgical insertion procedure was performed without further radiological
      investigation. Group C required other types of anchorage. In cases of an
      ambiguous bone situation (group B), further diagnostic procedures (CT/CBCT) were
      performed. RESULTS: During the observation period, 105 patients were screened.
      Fourteen patients opted for alternative treatment leaving 91 patients for final
      evaluation. In 89 patients (97.8%), the lateral radiographs showed sufficient
      bone in the vertical dimension. In all of these cases, the availability of
      sufficient bone was confirmed intraoperatively. Further investigations were
      performed in two patients (2.2%) of group B (one CT, one CBCT). Finally, one
      patient had insufficient bone whereas the second had sufficient bone.
      CONCLUSIONS: Nearly 98% of the patients included in this study had sufficient
      bone for palatal implant insertion. Lateral radiographs permit correct and
      reliable evaluation of the quantity of bone in preoperative diagnosis of palatal
      implants. Additional imaging (CT or CBCT) is only required in rare cases of
      borderline dimensions.

PMID- 20132246
TI  - Regenerative treatment of peri-implantitis bone defects with a combination of
      autologous bone and a demineralized xenogenic bone graft: a series of 36 defects.
AB  - AIM: As the treatment of peri-implantitis-induced bone loss is still a problem,
      we studied the regenerative treatment of these defects with a mix of autologous
      bone and a new type of bone graft substitute (demineralized xenogenic bone graft)
      including growth factors. MATERIAL AND METHODS: In a prospective manner, 36 cases
      of peri-implantitis-induced bone loss (depth >4 mm) in 22 patients were followed
      for 1 year. After resolving the acute infection by local rinsing, granulation
      tissue was removed. The implants were decontaminated with etching gel and the
      defects were filled with autologous bone mixed 1:1 with a xenogenic bone graft.
      The prosthetic reconstructions did not have to be removed. Values of probing
      depths as well as bone defects were analyzed. RESULTS: The radiologic evaluation
      of the bone defects after regenerative treatment revealed a mean reduction of 3.5
      mm comparing the values from 5.1 mm prior to surgery to 1.6 mm 1 year after
      treatment. Average reduction of the probing depth was 4 mm. The remaining bone
      defects were larger than 3 mm in 4 out of 36 implants 1 year after treatment.
      Probing depths of more than 4 mm were present in seven implants. CONCLUSION:
      Within the limits of the study, we conclude that for bone defects larger than 4
      mm in case of peri-implantitis, this single surgical intervention provided a
      reliable method to reduce bone defects.

PMID- 20132247
TI  - The effect of platelet-rich plasma on healing of palatal donor site following
      connective tissue harvesting: a pilot study in dogs.
AB  - BACKGROUND: Peri-implant plastic surgery includes soft tissue enhancement by
      connective tissue grafting. The palatal donor site provides peri-implant
      keratinized mucosa and soft tissue height. Platelet-rich plasma (PRP) contains
      growth factors that may enhance early healing. PURPOSE: The present animal study
      investigated the effect of PRP on wound healing of palatal donor site after
      connective tissue harvesting. MATERIALS AND METHODS: In 12 mongrel dogs,
      bilateral palatal connective tissues of 10 * 15 mm were harvested. At test site,
      PRP was applied into the wound, and the contralateral site served as control. The
      healing was evaluated clinically and histologically at 1 week, 2 weeks, and 4
      weeks after surgeries. Exact binomial probability and Wilcoxon signed-rank test
      were used to compare the clinical and histologic measurements. RESULTS: No
      statistically significant differences between PRP and control sites were measured
      with regard to clinical healing (p = 1.000) and histologic variables, including
      inflammatory cells (p = .750), collagen fibers (p = .375), and granulation tissue
      (p = .500) at any time interval. CONCLUSION: The addition of PRP to palatal
      mucosal wound sites did not accelerate wound healing.

PMID- 20132248
TI  - Novel H1N1-associated rhabdomyolysis leading to acute renal failure.
AB  - The WHO recently declared that the novel influenza H1N1 virus was responsible for
      the 2009 flu pandemic. As the virus continues to spread globally and affect more
      individuals, more complications of infection with this virus are being
      recognized. To our knowledge, we report the first case of H1N1-induced
      rhabdomyolysis leading to acute renal failure in an adult. This case highlights
      the importance of recognizing a significant extrapulmonary complication of H1N1
      infection.

PMID- 20132249
TI  - Curtailed short-term and long-term survival following infection with non-typhoid
      Salmonella in Israel.
AB  - Among bacterial foodborne pathogens, non-typhoid Salmonella enterica (NTS) is a
      leading cause of death worldwide. This study assessed short-term and long-term
      mortality following NTS infection in Israel, and evaluated the effects of age,
      sex, source of isolation and different serotypes on mortality. The source of data
      was a national registry of NTS isolates submitted to the Salmonella Reference
      Center, Government Central Laboratories, in Jerusalem, Israel, during 1997-2006.
      Vital status was derived from the registry of the Israeli Ministry of the
      Interior. The survival of a cohort of 15,919 patients infected with the top five
      NTS serotypes was evaluated by calculating age-standardized mortality ratios
      (SMRs) and by Cox proportional hazards multivariate regressions at three follow
      up time intervals: 30 days, 1 year and end of follow-up. The median follow-up
      time was 6.44 years (mean, 6.21 years; range, 1 day to 10.80 years). The
      cumulative crude mortality rates at the three time intervals were 0.68%, 1.86%
      and 4.40%, respectively, corresponding to increased SMRs of 16.95 (95% CI 13.9
      20.46), 4.25 (95% CI 3.78-4.76), and 1.83 (95% CI 1.70-1.97), respectively. Cox
      regressions revealed that increasing age, extraintestinal source of isolation and
      NTS serotype had significant effects on mortality within all three follow-up
      intervals. The risk of mortality was increased for serotypes Infantis and
      Typhimurium, and decreased for serotypes Virchow and Hadar, as compared with
      serotype Enteritidis. The study revealed curtailed short-term and long-term
      survival following NTS infection that persisted for many years following
      detection by culture.

PMID- 20132250
TI  - Streptococcus pneumoniae: virulence factors and variation.
AB  - Streptococcus pneumoniae is a major pathogen of humans, causing diseases such as
      pneumonia and meningitis. The organism produces several virulence factors that
      are involved in the disease process. The molecular basis of the action of some of
      these virulence factors is being elucidated. The advent of whole genome
      sequencing combined with biological studies has demonstrated that genome
      variation is important in the ability of pneumococci to interact with the host.
      This review discusses the biological activity of several pneumococcal virulence
      factors, and describes how genome variation may impact on the ability of
      pneumococci to cause disease.

PMID- 20132251
TI  - Changes in antimicrobial resistance, serotypes and genotypes in Streptococcus
      pneumoniae over a 30-year period.
AB  - Over the past three decades, antimicrobial resistance in Streptococcus pneumoniae
      has dramatically increased worldwide. Non-susceptibility to penicillin in S.
      pneumoniae was first described in Australia in 1967, and later in New Guinea
      (1974), South Africa (1977), and Spain (1979). Most of these strains showed
      resistance to multiple antibiotics and belonged to serotypes 6A, 6B, 19A, 19F,
      and 23F. By the late 1980s and 1990s, the emergence and rapid dissemination of
      antibiotic-resistant pneumococci was observed in southern and eastern Europe,
      North America, South America, Africa, and Asia. Great geographical variability,
      both in serotype distribution and in the prevalence of resistant pneumococci, has
      been reported. However, the highest rates of resistance to penicillin and
      erythromycin worldwide were found in serotypes 6B, 6A, 9V, 14, 15A, 19F, 19A, and
      23F. The introduction of the seven-valent pneumococcal conjugate vaccine (PCV7)
      in the 2000s and a reduction in antimicrobial use were associated with a
      significant decline in the incidence of invasive pneumococcal infections and in
      rates of antibiotic resistance in the USA. However, an increase in the incidence
      of infections caused by non-PCV7 serotypes, especially multiresistant serotype
      19A pneumococci, has been observed in many countries over the last 5 years. The
      dynamic character of serotypes and antibiotic resistance in S. pneumoniae should
      be controlled by a policy of prudent antibiotic use and by implementation of the
      new generation of conjugate vaccines.

PMID- 20132252
TI  - Evaluation of matrix-assisted laser desorption ionization-time-of-flight mass
      spectrometry in comparison to rpoB gene sequencing for species identification of
      bloodstream infection staphylococcal isolates.
AB  - As a result of variable expression of biochemical characters, misidentification
      by conventional phenotypic means often occurs with clinical isolates belonging to
      Staphylococcus species. Therefore, we evaluated the use of matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) for the
      identification of 450 blood isolates of the most relevant staphylococcal species,
      using sequence analysis of the rpoB gene as the reference method. A correct
      species identification by MALDI-TOF was obtained in 99.3% (447/450), with only
      three isolates being misidentified. In addition, MALDI-TOF correctly identified
      all the staphylococcal subspecies studied, including Staphylococcus capitis
      subsp. capitis and subsp. urealyticus, Staphylococcus cohnii subsp. urealyticus,
      Staphylococcus hominis subsp. novobiosepticus and subsp. hominis, Staphylococcus
      saprophyticus subsp. saprophyticus, Staphylococcus schleiferi subsp. schleiferi
      and Staphylococcus sciuri subsp. sciuri. Thus, MALDI-TOF MS-based species
      identification of staphylococci can be routinely achieved without any substantial
      costs for consumables or the time needed for labour-intensive DNA sequence
      analysis.

PMID- 20132253
TI  - Genitourinary infections caused by nontuberculous mycobacteria at a university
      hospital in Taiwan, 1996-2008.
AB  - Genitourinary infections caused by nontuberculous mycobacteria (NTM) are rarely
      reported. The medical records of all patients with genitourinary NTM infections
      treated at National Taiwan University Hospital from 1996-2008 were
      retrospectively reviewed. Fifteen patients were identified, of whom 10 (67%) were
      male. More than two-thirds of patients had underlying conditions, the most common
      of which was chronic renal disease. Only one patient had AIDS. Acid-fast smears
      of urine were negative in all patients. Eleven isolates were available for
      further confirmation by sequencing of the 16S rRNA gene. Mycobacterium avium
      complex was the most common (n = 5, 33%), followed by both Mycobacterium
      abscessus (n = 2; 13%) and Mycobacterium fortuitum (n = 2; 13%). Of the 12
      patients receiving anti-NTM treatment, only four received adequate prescribed
      regimens and none died of NTM infections. Two patients died of refractory
      urosepsis before the urinary NTM infections were diagnosed. The clinical
      characteristics of the 15 patients were also compared with 43 previously reported
      patients with genitourinary tuberculosis. Patients with genitourinary NTM
      infections were more likely to report constitutional symptoms, seek medical help
      within 1 month after the onset of symptoms and develop leukocytosis. Patients
      with genitourinary tuberculosis were more likely to have ureteral strictures and
      abnormal chest radiographs associated with active or inactive tuberculosis.
      Although rare, genitourinary NTM infections pose a significant threat to life and
      should be considered in the differential diagnosis of genitourinary infections,
      especially when patients are unresponsive to conventional antibiotic treatment.

PMID- 20132254
TI  - Junior doctors' knowledge and perceptions of antibiotic resistance and
      prescribing: a survey in France and Scotland.
AB  - Our objective was to assess junior doctors' perceptions of their antibiotic
      prescribing practice and of bacterial resistance. We surveyed 190 postgraduate
      doctors still in training at two university teaching hospitals, in Nice (France)
      and Dundee (Scotland, UK), and 139 of them (73%) responded to the survey. The
      main results presented in this abstract are combined for Nice and Dundee, because
      there was no statistical difference for these points between the two hospitals.
      Antibiotic resistance was perceived as a national problem by 95% of the junior
      doctors, but only 63% rated the problem as important in their own daily practice.
      Their perceptions of the causes of antibiotic resistance were sometimes at
      variance with available medical evidence, with excessive duration of antibiotic
      treatment and poor hand hygiene practices rarely being perceived as important
      drivers for resistance. Only 31% and 26% of the doctors knew the correct
      prevalences of antibiotic misuse and of methicillin-resistant Staphylococcus
      aureus in hospitals, respectively. They preferred educational interventions, such
      as specific teaching sessions, availability of guidelines or readily accessible
      advice from an infectious diseases specialist, to improve antibiotic prescribing,
      rather than restricted prescription of antibiotics. These data provide helpful
      information for the design of strategies to optimize adherence to good
      antimicrobial stewardship.

PMID- 20132255
TI  - Rapid field detection assays for Bacillus anthracis, Brucella spp., Francisella
      tularensis and Yersinia pestis.
AB  - Rapid detection is essential for timely initiation of medical post-exposure
      prophylactic measures in the event of intentional release of biological threat
      agents. We compared real-time PCR assay performance between the Applied
      Biosystems 7300/7500 and the RAZOR instruments for specific detection of the
      causative agents of anthrax, brucellosis, tularemia and plague. Furthermore, an
      assay detecting Bacillus thuringiensis, a Bacillus anthracis surrogate, was
      developed for field-training purposes. Assay sensitivities for B. anthracis,
      Brucella spp., Francisella tularensis and Yersinia pestis were 10-100 fg of
      target DNA per reaction, and no significant difference in assay performance was
      observed between the instrument platforms. Specificity testing of the diagnostic
      panels with both instrument platforms did not reveal any cross-reactivity with
      other closely related bacteria. The duration of thermocycling with the RAZOR
      instrument was shorter, i.e. 40 min as compared with 100 min for the Applied
      Biosystems 7300/7500 instruments. These assays provide rapid tools for the
      specific detection of four biological threat agents. The detection assays, as
      well as the training assay for B. thuringiensis powder preparation analysis, may
      be utilized under field conditions and for field training, respectively.

PMID- 20132256
TI  - Analysis of quorum sensing-dependent virulence factor production and its
      relationship with antimicrobial susceptibility in Pseudomonas aeruginosa
      respiratory isolates.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen causing severe respiratory
      infections. The pathogenesis of these infections is multifactorial and the
      production of many virulence factors is regulated by quorum sensing (QS), a cell
      to-cell communication mechanism. The two well defined QS systems in P.
      aeruginosa, the las and rhl systems, rely on N-acyl homoserine lactone signal
      molecules, also termed autoinducers. We assessed the activity of QS-dependent
      virulence factors (including elastase, alkaline protease, pyocyanin and biofilm
      production) in respiratory isolates of P. aeruginosa and their relationship with
      antimicrobial susceptibility. We identified sixteen isolates displaying impaired
      phenotypic activity; among them, eleven isolates were also defective in
      autoinducer production, and therefore considered QS-deficient. Six of the QS
      deficient isolates failed to amplify one or more of the four QS regulatory genes
      (lasI, lasR, rhlI, rhlR) with PCR: one isolate was negative for rhlR, two
      isolates were negative for rhlI and rhlR and three isolates were negative for all
      four genes. The isolates that were negative for virulence factor production were
      generally less susceptible to the antimicrobials and statistically significant
      correlations were observed between the lack of elastase production and resistance
      to piperacillin and ceftazidime; between failure in alkaline protease production
      and resistance to tobramycin, piperacillin, piperacillin-tazobactam, cefepime,
      imipenem and ciprofloxacin; and between failure in pyocyanin production and
      resistance to amikacin, tobramycin, ceftazidime, ciprofloxacin and ofloxacin. The
      results obtained indicate that, despite the pivotal role of QS in the
      pathogenesis of P. aeruginosa respiratory infections, QS-deficient strains are
      still capable of causing infections and tend to be less susceptible to
      antimicrobials.

PMID- 20132257
TI  - Cerebral function tests reveal differences in HIV-infected subjects with and
      without chronic HCV co-infection.
AB  - Neurocognitive impairment (NCI) remains prevalent in HIV-infected subjects
      despite effective combination antiretroviral therapy (CART). In subjects without
      evidence of hepatic decompensation, NCI is also a feature of chronic HCV
      infection. The present study aimed to examine cerebral function and establish
      differences between HIV-HCV co-infected (HCVco) and HIV mono-infected (HIVmo)
      individuals. Neurologically asymptomatic subjects with chronic HCVco were
      eligible and underwent computerized neurocognitive testing (CogState; CogState
      Ltd, Melbourne, Australia), a dementia assessment [International HIV Dementia
      Scale (IHDS)] and memory assessment [the Prospective and Retrospective Memory
      Questionnaire (PRMQ)]. Historic control data were available for 45 HIVmo
      individuals and differences between study groups were assessed. Twenty-seven
      HCVco subjects were recruited. Plasma HIV RNA was <50 copies/mL in 25/27 of HCVco
      subjects and all HIVmo subjects and nadir CD4+ cell count (mean +/- SD) was 214
      +/- 166 cells/MUL and 180 +/- 130 cells/MUL, in HCVco and HIVmo subjects,
      respectively. No statistically significant differences in neurocognitive
      parameters or PRMQ scores were observed between groups. However, a trend towards
      poorer executive function score was observed in HCVco subjects (p 0.106). IHDS
      score (mean +/- SD) was poorer in HCVco subjects (10.48 +/- 1.25) vs. HIVmo
      subjects (11.51 +/- 0.76), (p <0.001). In a multivariate model, increasing age
      and HCVco were the only factors significantly associated with poorer IHDS scores
      (p 0.039 and <0.001, respectively). In HIV-infected subjects stable on CART,
      statistically significantly poorer performance in the IHDS score was observed in
      subjects with HCVco, although no differences were observed after neurocognitive
      testing or memory assessment.

PMID- 20132258
TI  - Lyme borreliosis: clinical case definitions for diagnosis and management in
      Europe.
AB  - Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies
      complex, is the most commonly reported tick-borne infection in Europe and North
      America. The non-specific nature of many of its clinical manifestations presents
      a diagnostic challenge and concise case definitions are essential for its
      satisfactory management. Lyme borreliosis is very similar in Europe and North
      America but the greater variety of genospecies in Europe leads to some important
      differences in clinical presentation. These new case definitions for European
      Lyme borreliosis emphasise recognition of clinical manifestations supported by
      relevant laboratory criteria and may be used in a clinical setting and also for
      epidemiological investigations.

PMID- 20132259
TI  - Epidemiological markers of Streptococcus pyogenes strains in Tunisia.
AB  - To further understand the epidemiology of Streptococcus pyogenes or group A
      streptococcus (GAS) infections in Tunisia, phenotypic and genomic markers of GAS
      isolates, including antibiotic susceptibility, biotypes, T and emm types and
      toxin gene profiles, have been characterized. A total of 103 isolates, collected
      between 2000 and 2006, were investigated; 47 were recovered from invasive
      infections, and 56 from non-invasive infections. Rates of resistance to
      tetracycline, erythromycin, clindamycin and rifampin were 70.8%, 4.8%, 4.8% and
      0.9%, respectively. High levels of resistance to streptomycin and kanamycin were
      observed in 1.9% and 4.8% of isolates, respectively. Biotype 3 was most common.
      Twenty different T patterns were observed, with a predominance of T3/13/B3264,
      and 38 different emm types. In both invasive and non-invasive isolates, emm118
      (9.7%), emm42 (8.7%), emm1 (7.8%), st432 (6.8%), emm28 (5.8%) and emm76 (5.8%)
      were the most prevalent types; emm1, emm76 and emm18 were mainly observed among
      invasive infections, whereas emm118 (12.5%), emm42 (10.7%) and emm28 (8.9%) were
      predominant among non-invasive infections. The speB gene was detected in all
      isolates, but there were variable frequencies of speA, speC and ssa (20.3%, 32%
      and 25.2% respectively). Significant associations of emm1, emm18 and emm3 with
      speA and of emm4 and st432 with ssa were found. This first report from Tunisia
      revealed a unique emm distribution of GAS that differs from those of other
      regions. This information on the distribution of such emm types will be useful
      for the development of an appropriate vaccine in a country where the incidence of
      rheumatic fever remains high.

PMID- 20132260
TI  - Isolation of Mycobacterium bolletii from human omentum after laparoscopic gastric
      banding.
AB  - Mycobacterium bolletii infection with band erosion complicating laparoscopic
      gastric banding is reported. A 33-year-old man developed right upper quadrant
      pain and an epigastric discharging lesion 4 weeks after revision of gastric
      banding for morbid obesity. Investigation revealed band erosion with infection of
      the omentum and the abdominal wall. The band was removed and M. bolletii was
      isolated and identified after DNA sequence analysis. To the best of our
      knowledge, this is the first case in which M. bolletii was isolated from a human
      omentum after complicated gastric banding surgery.

PMID- 20132261
TI  - Commentary: Lymph node retrieval in colorectal cancer specimens: national
      standards are achievable, and low numbers are associated with reduced survival.

PMID- 20132262
TI  - Considerations about STARR and Contour Transtar.

PMID- 20132263
TI  - Imprint cytology of primary ethmoidal lipid-rich carcinoma combined with
      adipophilin immunocytochemistry.

PMID- 20132264
TI  - Humanitarian presence and urban development: new opportunities and contrasts in
      Goma, DRC.
AB  - This paper examines the impact of the presence of international humanitarian
      organisations on local urban transformation processes in the city of Goma,
      Democratic Republic of the Congo (DRC). Rather than evaluating the direct effects
      of humanitarian interventions and strategies, it focuses on the indirect but
      profound effects of the presence of this 'humanitarian sector'. It argues that
      the international humanitarian presence became a significant factor in the recent
      shaping and reshaping of the city's profile and has reinforced competition over
      the urban political and socioeconomic space. The paper evaluates the direct and
      indirect impact of the international humanitarian presence on the local urban
      economy and the larger political economy of war in eastern DRC. It analyses how
      this presence has reinforced processes of spatial reconfiguration, how it has
      influenced urban planning, and how it has affected dynamics of gentrification and
      marginalisation on the urban spatial level.

PMID- 20132265
TI  - Between protest, revenge and material interests: a phenomenological analysis of
      looting in the Somali war.
AB  - This paper examines practices of looting in the Somali war. Rather than being
      inspired primarily by economic objectives, lootings are complex and ambiguous
      social activities, which are embedded in daily practices and the political
      rhetoric of the war. In Somalia, looting activities have been driven by a broad
      range of motives, including military-strategic considerations and/or desire to
      revenge past atrocities and (perceived) injustices, as well as economic
      interests. Furthermore, the organisational structure, the performance of actions
      and the main targets of looters have differed widely. Based on an empirical
      analysis of different waves and phases of looting in the context of war and state
      decay in Somalia, the paper identifies five types of looting. Beyond a state
      centred conceptualisation of order, the study reveals that looting is not an
      expression of political chaos, but rather is patterned by and rooted in local
      moral universes, which have been fundamentally transformed during the course of
      the violent conflicts in the country since the end of the 1970s.

PMID- 20132266
TI  - The far side: the meta functions of humanitarianism in a globalised world.
AB  - This paper explores the meta functions of humanitarianism--that is, the functions
      that, as an ideology, a movement and a profession, it performs, wittingly or
      unwittingly, in the early twenty-first century. The term humanitarianism is used
      as shorthand to encompass a complex set of currents of thought, actions and
      institutions of which the boundaries are unclear. The focus is on mainstream
      humanitarianism, the dominant Northern/Western enterprise. The paper first
      discusses the relationship between humanitarianism and globalised power. It goes
      on to examine three types of functions that humanitarianism and humanitarian
      action perform: 'macro' functions--the deep undercurrents, power relations and
      values that humanitarianism articulates and transmits; 'meso' functions--those
      that relate to the political economy of humanitarian action and to the mechanics
      (rather than to the ideology) of globalisation; and 'micro' functions that relate
      to the motivations of the individuals who devote their energies to
      humanitarianism.

PMID- 20132267
TI  - Learning from recovery after Hurricane Mitch.
AB  - This paper reviews how Nicaragua has recovered from Hurricane Mitch of October
      1998. In particular, it examines how the assumptions and claims that were made
      during initial recovery planning have proven relevant in light of subsequent
      development. One must consider the response to Hurricane Mitch from the
      perspective of the broader trends that have driven recovery, including household,
      community and government initiatives and the wider economic context. Recovery
      efforts have not 'transformed' Nicaragua. In fact, market upheavals and
      livelihood changes in rural areas have had a more profound impact on poverty
      profiles than recovery programmes. Social protection programmes have been
      piloted, but patron-client ties and relations with aid providers are still more
      reliable sources of support in a time of crisis. Risk reduction has become more
      deeply integrated into the rural development discourse than was the case before
      the disaster, but risk reduction initiatives continue to place undue emphasis on
      hazard response rather than addressing vulnerability.

PMID- 20132268
TI  - The humanitarian arena in Angola, 1975-2008.
AB  - In conflict and post-conflict societies, service delivery is complex both in
      terms of actors and of the kinds of services provided. The dominant framework of
      humanitarian space, with its strong focus on international humanitarian
      assistance and on humanitarian principles, does not fully capture the dynamics
      and process of service delivery. This paper proposes an alternative analytical
      framework that depicts humanitarian space as an arena where aid is negotiated and
      its outcomes shaped by the interaction of various social actors. It reviews the
      history of service delivery in Angola and shows that during different conflict
      and post-conflict phases, a range of actors and service types that fall outside
      of those labelled as humanitarian were essential in addressing local needs.
      Stepping away from normative expectations of what happens during humanitarian
      crises reveals how service delivery gets shaped in everyday practice and provides
      an alternative understanding of crises response.

PMID- 20132269
TI  - Livelihoods and protection in situations of protracted conflict.
AB  - This paper presents the findings from research on livelihoods-protection linkages
      from the perspective of conflict-affected populations as well as agency analysis
      and action. The aim of the research is to understand how greater complementarity
      between humanitarian protection and livelihoods approaches might reduce the risks
      facing conflict-affected populations. The findings show that the causes of risks
      to livelihoods and protection are often the same, and that community responses
      are intimately connected, providing good rationale for linking operational
      approaches. There are four main ways in which this can be done. First, by
      targeting those confronting the greatest risks. Second, by addressing the causes
      of risks through advocacy and capacity-building. Third, by implementing
      livelihoods interventions that minimise the need to adopt unsafe livelihood
      strategies and that address humanitarian consequences. Fourth, by making sure
      that livelihoods programming does not pose additional risks.

PMID- 20132270
TI  - Forced displacement and women's security in Colombia.
AB  - In the protracted Colombian conflict, assistance to internally displaced persons
      has developed in the context of contradictory political processes. The Colombian
      government's launching of a transitional justice process in the midst of armed
      conflict has generated a complex situation displaying both conflict and post
      conflict characteristics. The progressive Constitutional Court rulings on
      internal displacement, in particular the gender-sensitive Auto 092, constitute an
      attempt to bring together humanitarian interventions and transitional justice
      measures in a rights-based framework. However, the national government is
      reluctant to adopt them fully and local realities still hamper their integrated
      implementation. Displaced women, therefore, remain in an especially vulnerable
      position. This paper argues that gender-sensitive humanitarian interventions must
      take into account all of these complexities of scale and political process in
      order to make legal frameworks more effective at the local level. In these
      contexts, interventions should pay particular attention to strategies that
      contribute to transforming pre-existing gender regimes.

PMID- 20132271
TI  - Ritual dynamics in humanitarian assistance.
AB  - Those who intervene in crises must take care to ensure that assistance does not
      undermine the processes through which social cohesion is generated or restored.
      From a neo-Durkheimian analytical perspective, feeding creates social loyalties
      as well as saves lives. Humanitarian agencies provide practical assistance to
      livelihoods, but they need also to create space for the ritual agency on which
      social cohesion depends. Attention to the rituals of food distribution helps
      humanitarian actors to address a potentially damaging dissociation between social
      and material facts. A post-war food security project in Sierra Leone is used to
      illustrate the point. The lessons of this intervention have implications for the
      organisation of humanitarian assistance at all levels, both international and
      local. The paper argues that establishing space for ritualisation within
      humanitarian programmes is an obligation for those who wish to do no harm.

PMID- 20132272
TI  - The humanitarians' tragedy: escapable and inescapable cruelties.
AB  - Paradoxically, elements of cruelty are intrinsic to the humanitarian
      enterprise.(1) This paper focuses on some of these. Escapable cruelties arise
      from technical failings, but the gradual professionalisation of the field and
      improvements in relief technologies mean that they have been significantly
      reduced in comparison to earlier eras. Other cruelties arise from clashes among
      rights, and the tensions inherent in trying to promote humanity amid the horrors
      of war. These are inescapable and constitute the 'humanitarians' tragedy'. Among
      them is the individual cruelty of failing to do good at the margin: a clash
      between the individual's impulses and ideals and the constraints of operating in
      constrained circumstances. This is a version of triage. In addition, there is the
      cruelty of compromising dearly-held principles when faced with other competing or
      overriding demands. There is also the cruelty whereby humanitarians feed victims'
      dreams that there is an alternative reality, which in fact cannot be attained.

PMID- 20132273
TI  - Editorial: Social dynamics of humanitarian action.

PMID- 20132274
TI  - Factors driving pathogenicity vs. prevalence of amphibian panzootic
      chytridiomycosis in Iberia.
AB  - Amphibian chytridiomycosis is a disease caused by the fungus Batrachochytrium
      dendrobatidis (Bd). Whether Bd is a new emerging pathogen (the novel pathogen
      hypothesis; NPH) or whether environmental changes are exacerbating the host
      pathogen dynamic (the endemic pathogen hypothesis; EPH) is debated. To
      disentangle these hypotheses we map the distribution of Bd and chytridiomycosis
      across the Iberian Peninsula centred on the first European outbreak site. We find
      that the infection-free state is the norm across both sample sites and
      individuals. To analyse this dataset, we use Bayesian zero-inflated binomial
      models to test whether environmental variables can account for heterogeneity in
      both the presence and prevalence of Bd, and heterogeneity in the occurrence of
      the disease, chytridiomycosis. We also search for signatures of Bd-spread within
      Iberia using genotyping. We show (1) no evidence for any relationship between the
      presence of Bd and environmental variables, (2) a weak relationship between
      environmental variables and the conditional prevalence of infection, (3) stage
      dependent heterogeneity in the infection risk, (4) a strong association between
      altitude and chytridiomycosis, (5) multiple Iberian genotypes and (6) recent
      introduction and spread of a single genotype of Bd in the Pyrenees. We conclude
      that the NPH is consistent with the emergence of Bd in Iberia. However, epizootic
      forcing of infection is tied to location and shaped by both biotic and abiotic
      variables. Therefore, the population-level consequences of disease introduction
      are explained by EPH-like processes. This study demonstrates the power of
      combining surveillance and molecular data to ascertain the drivers of new
      emerging infections diseases.

PMID- 20132275
TI  - Abstracts of 26th Annual Scientific Meeting of the Australasian College for
      Emergency Medicine. Melbourne, Victoria, Australia. November 15-19, 2009.

PMID- 20132276
TI  - Karst pools in subsurface environments: collectors of microbial diversity or
      temporary residence between habitat types.
AB  - We studied bacterial diversity and community composition in three shallow pools
      of a Swiss karst cave system with contrasting hydrological and hydrochemical
      properties. The microbial assemblages in the pools were remarkably different, and
      only one operational taxonomic unit of 16S rRNA genes (OTU, 97% similarity) was
      shared between the three of them (total OTU number in all pools: 150).
      Unexpectedly high microbial phylotype richness was found even in the two pools
      without groundwater contact and with low concentrations of organic carbon and
      total cell numbers (< 10(4) ml(-1)). One of these seepage water fed systems
      harboured 15 distinct OTUs from several deeply branching lineages of the
      candidate phylum OP3, whereas representatives of this group were not detected in
      the other two pools. A tentative phylogeographic analysis of available OP3
      related sequences in the context of our data set revealed that there was
      generally little agreement between the habitats of origin of closely related
      sequence types. Two bacterial clades affiliated with the obligate methylamine
      utilizer Methylotenera mobilis were only found in the pool that was exposed to
      repeated flooding events. These bacteria formed relatively stable populations of
      up to 6% of total cell counts over periods of several months irrespective of
      inundation by groundwater. This suggests that karst water may provide a means of
      transport for these bacteria from terrestrial to freshwater habitats.

PMID- 20132277
TI  - Transcriptional studies of the hrpM/opgH gene in Pseudomonas syringae during
      biofilm formation and in response to different environmental challenges.
AB  - Pseudomonas syringae pv. syringae strain FF5 is a phytopathogen that causes a
      rapid dieback on ornamental pear trees. In the present study, the transcriptional
      expression of hrpM/opgH, algD, hrpR and rpoD was evaluated in P. syringae FF5 and
      FF5.M2 (hrpM/opgH mutant). The temporal expression of these genes was evaluated
      during biofilm formation, the hypersensitive reaction (HR) on tobacco plants, and
      when the bacteria were subjected to different environmental stresses. The results
      indicate that mutations in hrpM negatively impair several traits including
      biofilm formation, the ability to cause disease in host plants and the HR in non
      host plants, and the expression of hrpR, a regulatory gene modulating the latter
      two traits. Furthermore, FF5.M2 was decreased in swarming motility and unable to
      respond to different environmental challenges. Interestingly, FF5.M2 showed an
      exponential increase in the expression of algD, which is the first gene to be
      transcribed during the biosynthesis of the alginate, a virulence factor in P.
      syringae. The expression of both hrpM and algD were required for biofilm
      formation, and hrpM was expressed earlier than algD during biofilm development.
      These findings indicate that hrpM expression is required for several traits in P.
      syringae and plays an important role in how this bacterium responds to
      environmental challenges.

PMID- 20132278
TI  - Human sewage identified as likely source of white pox disease of the threatened
      Caribbean elkhorn coral, Acropora palmata.
AB  - Caribbean elkhorn coral, Acropora palmata, has been decimated in recent years,
      resulting in the listing of this species as threatened under the United States
      Endangered Species Act. A major contributing factor in the decline of this iconic
      species is white pox disease. In 2002, we identified the faecal enterobacterium,
      Serratia marcescens, as an etiological agent for white pox. During outbreaks in
      2003 a unique strain of S. marcescens was identified in both human sewage and
      white pox lesions. This strain (PDR60) was also identified from corallivorious
      snails (Coralliophila abbreviata), reef water, and two non-acroporid coral
      species, Siderastrea siderea and Solenastrea bournoni. Identification of PDR60 in
      sewage, diseased Acropora palmata and other reef invertebrates within a discrete
      time frame suggests a causal link between white pox and sewage contamination on
      reefs and supports the conclusion that humans are a likely source of this
      disease.

PMID- 20132279
TI  - Homologues of nitrite reductases in ammonia-oxidizing archaea: diversity and
      genomic context.
AB  - Ammonia-oxidizing archaea are frequent and ubiquitous inhabitants of terrestrial
      and marine environments. As they have only recently been detected, most aspects
      of their metabolism are yet unknown. Here we report on the occurrence of genes
      encoding potential homologues of copper-dependent nitrite reductases (NirK) in
      ammonia-oxidizing archaea of soils and other environments using metagenomic
      approaches and PCR amplification. Two pairs of highly overlapping 40 kb genome
      fragments, each containing nirK genes of archaea, were isolated from a
      metagenomic soil library. Between 68% and 85% of the open reading frames on these
      genome fragments had homologues in the genomes of the marine archaeal ammonia
      oxidizers Nitrosopumilus maritimus and Cenarchaeum symbiosum. Extensions of NirK
      homologues with C-terminal fused amicyanin domains were deduced from two of the
      four fosmids indicating structural variation of these multicopper proteins in
      archaea. Phylogenetic analyses including all major groups of currently known NirK
      homologues revealed that the deduced protein sequences of marine and soil archaea
      were separated into two highly divergent lineages that did not contain bacterial
      homologues. In contrast, another separated lineage contained potential
      multicopper oxidases of both domains, archaea and bacteria. More nirK gene
      variants directly amplified by PCR from several environments indicated further
      diversity of the gene and a widespread occurrence in archaea. Transcription of
      the potential archaeal nirK in soil was demonstrated at different water contents,
      but no significant increase in transcript copy number was observed with increased
      denitrifying activity.

PMID- 20132280
TI  - Nitrogen fixation by a marine non-heterocystous cyanobacterium requires a
      heterotrophic bacterial consort.
AB  - Cultures of the non-heterocystous cyanobacterium, Leptolyngbya nodulosa, could be
      grown indefinitely in media devoid of combined nitrogen. Acetylene reduction
      assays showed that these cultures fixed nitrogen in the dark period of a diurnal
      cycle under micro-oxygenic or anaerobic conditions. Addition of DCMU to cultures
      induced much higher rates of nitrogenase activity, most of which occurred in the
      light. Measurements of activity in the presence of chloramphenicol indicated that
      nitrogenase is synthesized in darkness and probably destroyed in the subsequent
      light period. Neither the dark-mediated nitrogenase in the absence of DCMU nor
      light-mediated activity in the presence of DCMU could be sustained for more than
      3 days without a photoperiodic light/dark cycle. Axenic cultures could not be
      grown in the absence of combined nitrogen and did not demonstrate any acetylene
      reduction activity. An identical nifH gene sequence was found in axenic and non
      axenic cultures of L. nodulosa. RT-PCR demonstrated that this gene was expressed
      only in non-axenic cultures. Western blotting showed that the Fe-protein of
      nitrogenase is absent in cultures that are incapable of acetylene reduction,
      indicating that the lack of nitrogenase activity is likely due to the absence of
      the enzyme. These observations strongly indicate that L. nodulosa contains a
      functional nitrogenase which is not expressed in the absence of heterotrophic
      bacteria.

PMID- 20132281
TI  - Characterization of halotolerant Bicosoecida and Placididea (Stramenopila) that
      are distinct from marine forms, and the phylogenetic pattern of salinity
      preference in heterotrophic stramenopiles.
AB  - Recent culture-based studies demonstrate the distinctiveness of the microbial
      eukaryote biota of very hypersaline environments. In contrast, microscopy-based
      faunistic studies suggest that the biota of habitats of more moderate
      hypersalinity (60-150 per thousand) overlaps substantially with that of marine
      environments, but this has barely been studied with modern techniques. To
      investigate the diversity and salinity tolerance range of these organisms, eight
      cultures of heterotrophic stramenopiles were established from (or from nearby)
      moderately hypersaline locations. These isolates represent five independent
      groups; Groups A, B and C are bicosoecids; Groups D and E belong to Placididea.
      One isolate (Group A) is a strain of the widespread marine species Cafeteria
      roenbergensis, and cannot grow above 100 per thousand salinity. The other
      isolates - Groups B-E - can all grow at 150-175 per thousand salinities and are
      probably moderate halophiles. Groups B-E all represent previously unsequenced
      species or even genera, although Group B is the sister group of the borderline
      extreme halophile Halocafeteria. The high level of novelty en countered suggests
      that moderately hypersaline environments may harbour a heterotrophic stramenopile
      biota distinct from that of marine environments. Interestingly, our new isolates
      are all most closely related to marine or halophilic forms, and our phylogenies
      show large clades defined by saline/non-saline habitats within bicosoecids,
      placidomonads and related lineages. In particular, most freshwater/soil
      bicosoecids form one well-supported clade. The sole major exception is Bicosoeca,
      which is intermixed with marine environmental sequences originally referred to as
      'MAST-13', which are from brackish water, not typical seawater. It seems that the
      freshwater/marine barrier has been crossed very few times in the evolutionary
      history of these heterotrophic stramenopile flagellates.

PMID- 20132282
TI  - Tantalizing evidence for caspase-like protein expression and activity in the
      cellular stress response of Archaea.
AB  - An enigmatic feature of microbial evolution is the emergence of programmed cell
      death (PCD), a genetically controlled form of cell suicide triggered by
      environmental stimuli. Archaea, the second major prokaryotic domain of life, have
      been notably absent from the PCD inheritance discussion, due to a lack of genetic
      homologues. Using the model haloarchaeon Haloferax volcanii, we document
      extremely high caspase-specific activity and expression of immunoreactive
      proteins to human caspase 8 antisera, both of which were induced by salt stress
      and death and were abolished by in vivo addition of a broad-spectrum caspase
      inhibitor. Caspase inhibition severely impaired cell growth under low and high
      salt stress, demonstrating a critical role in the cellular stress response. In
      silico analysis of the H. volcanii proteome identified a subset of 18 potential
      target proteins containing a signature tetrapeptide caspase cleavage motif
      (IETD), some with putative roles in allosteric regulation, signal transduction,
      osmotic stress and cell communication. Detection of similarly high activity and
      expression in other haloarchaea (Halorubrum and Haloarcula) and in diverse
      members of Euryarchaeota (the methanogen Methanosarcina acetivorans and the
      hyperthermophile Pyrococcus furiosus) and Crenarchaeota (the acidophile
      Sulfolobus solfataricus) argue for a broad representation within the archaeal
      domain. By playing a role in normal cell function, caspase-like proteases in
      Archaea appear to have co-evolved with other metabolic pathways, broadening their
      biological roles beyond apoptosis and cell death.

PMID- 20132283
TI  - Molecular characterization of inorganic sulfur-compound metabolism in the deep
      sea epsilonproteobacterium Sulfurovum sp. NBC37-1.
AB  - The molecular components involved in energy metabolism of deep-sea
      Epsilonproteobacteria were characterized in the mesophilic hydrogen- and sulfur
      oxidizing chemolithoautotroph Sulfurovum sp. NBC37-1. Previous whole-genome
      analysis of strain NBC37-1 identified key genes likely to be associated with both
      sulfur reduction (psr gene families) and oxidation (two sox gene clusters).
      However, the sox gene clusters showed unique organizations and low homologies to
      those in other bacteria. Therefore, the biochemical mechanism of inorganic sulfur
      metabolism has been uncertain. Enzymatic activity measurements and partial
      protein purification indicated that the Sox enzyme system was constitutively
      expressed, whereas the expression of sulfur-reduction enzymes varied depending on
      the culture conditions. The operative Sox system in strain NBC37-1 required
      membrane components. The molecular basis of energy metabolism reported in this
      study provides important insight into how deep-sea Epsilonproteobacteria change
      their energy metabolism in response to variable physical and chemical conditions
      in mixing zones between hydrothermal fluid and ambient seawater.

PMID- 20132284
TI  - The structure of bacterial communities in the western Arctic Ocean as revealed by
      pyrosequencing of 16S rRNA genes.
AB  - Bacterial communities in the surface layer of the oceans consist of a few
      abundant phylotypes and many rare ones, most with unknown ecological functions
      and unclear roles in biogeochemical processes. To test hypotheses about
      relationships between abundant and rare phylotypes, we examined bacterial
      communities in the western Arctic Ocean using pyrosequence data of the V6 region
      of the 16S rRNA gene. Samples were collected from various locations in the
      Chukchi Sea, the Beaufort Sea and Franklin Bay in summer and winter. We found
      that bacterial communities differed between summer and winter at a few locations,
      but overall there was no significant difference between the two seasons in spite
      of large differences in biogeochemical properties. The sequence data suggested
      that abundant phylotypes remained abundant while rare phylotypes remained rare
      between the two seasons and among the Arctic regions examined here, arguing
      against the 'seed bank' hypothesis. Phylotype richness was calculated for various
      bacterial groups defined by sequence similarity or by phylogeny (phyla and
      proteobacterial classes). Abundant bacterial groups had higher within-group
      diversity than rare groups, suggesting that the ecological success of a bacterial
      lineage depends on diversity rather than on the dominance of a few phylotypes. In
      these Arctic waters, in spite of dramatic variation in several biogeochemical
      properties, bacterial community structure was remarkably stable over time and
      among regions, and any variation was due to the abundant phylotypes rather than
      rare ones.

PMID- 20132285
TI  - Lacosamide as adjunctive therapy for partial-onset seizures: a randomized
      controlled trial.
AB  - PURPOSE: To evaluate the efficacy and safety of lacosamide (400 and 600 mg/day)
      as adjunctive treatment in patients with uncontrolled partial-onset seizures
      taking one to three concomitant antiepileptic drugs (AEDs). METHODS: This
      multicenter, double-blind, placebo-controlled trial randomized patients 1:2:1 to
      placebo, lacosamide 400 mg, or lacosamide 600 mg/day. After an 8-week baseline
      period, patients began treatment with placebo or lacosamide 100 mg/day, were
      force-titrated weekly (100 mg/day increments) to the target dose, and entered a
      12-week maintenance period. RESULTS: A total of 405 patients were randomized and
      received trial medication. Most (82.1%) were taking two to three concomitant
      AEDs. Median percent reductions in seizure frequency per 28 days from baseline to
      maintenance (intention-to-treat, ITT) were 37.3% for lacosamide 400 mg/day (p =
      0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for
      placebo, with responder rates of 38.3% and 41.2%, respectively, compared to
      placebo (18.3%, p < 0.001; ITT). Patients randomized to lacosamide showed large
      reductions in secondarily generalized tonic-clonic seizures, with median percent
      reductions in seizure frequency of 59.4% for lacosamide 400 mg/day and 93.0% for
      lacosamide 600 mg/day compared to 14.3% for placebo, and responder rates of 56.0%
      and 70.2% compared to placebo (33.3%). Dose-related adverse events included
      dizziness, nausea, and vomiting. DISCUSSION: Adjunctive treatment with lacosamide
      400 and 600 mg/day reduced seizure frequency for patients with uncontrolled
      partial-onset seizures. Lacosamide 400 mg/day provided a good balance of efficacy
      and tolerability; lacosamide 600 mg/day may provide additional benefit for some
      patients as suggested by secondary efficacy analyses, including response in
      patients with secondarily generalized tonic-clonic seizures.

PMID- 20132286
TI  - Interictal cerebral blood flow abnormality in cryptogenic West syndrome.
AB  - PURPOSE: To elucidate the abnormality of interictal regional cerebral blood flow
      (rCBF) of West syndrome at the onset. METHODS: Quantitative measurement of rCBF
      with an autoradiography method using N-isopropyl-((123)I) p-iodoamphetamine
      single photon emission computed tomography (SPECT) was performed on 14 infants
      with cryptogenic West syndrome. Regions of interest (ROIs) for rCBF were placed
      automatically using an automated ROI analysis software (three-dimensional
      stereotactic ROI template), and were grouped into 12 segments: callosomarginal,
      precentral, central, parietal, angular, temporal, posterior cerebral,
      pericallosal, lenticular nucleus, thalamus, hippocampus, and cerebellum. We
      compared rCBF between the patients and seven age-matched infants with cryptogenic
      focal epilepsy as a control group. The patients were divided into two groups
      according to the duration from onset to SPECT, to compare rCBF. RESULTS:
      Quantitative analysis revealed cerebral hypoperfusion in cryptogenic West
      syndrome with normal SPECT images under visual inspection. In bilateral central,
      posterior cerebral, pericallosal, lenticular nucleus, and hippocampus, and in the
      left parietal, temporal, and cerebellum, and in the right angular and thalamus
      segments there were statistical differences (p < 0.05). Compared with the
      duration from onset to SPECT, there were no significant differences of rCBF in
      all segments. DISCUSSION: Broad cerebral hypoperfusion with posterior
      predominance involving the hippocampus and lenticular nucleus implies that even
      cryptogenic West syndrome has a widespread cerebral dysfunction at least
      transiently, which would correspond to clinical manifestations of hypsarrhythmia
      and epileptic spasms. Hippocampal hypoperfusion suggests the dysfunction of
      hippocampal circuitry in the brain adrenal axis, and may contribute to subsequent
      cognitive impairment of cryptogenic West syndrome.

PMID- 20132287
TI  - Long-term outcomes of children treated with the ketogenic diet in the past.
AB  - PURPOSE: The ketogenic diet has well-established short- and long-term outcomes
      for children with intractable epilepsy, but only for those actively receiving it.
      However, no information exists about its long-term effects years after it has
      been discontinued. METHODS: Living subjects were identified who were treated at
      the Johns Hopkins Hospital with the ketogenic diet from November 1993 to December
      2008 for >or=1 month, and had discontinued it >or=6 months prior to this study.
      Of 530 patients who were eligible, 254 were successfully contacted by phone or e
      mail with a survey and request for laboratory studies. RESULTS: Questionnaires
      were completed by 101 patients, with a median current age of 13 years (range 2-26
      years). Median time since discontinuing the ketogenic diet was 6 years (range 0.8
      14 years). Few (8%) still preferred to eat high fat foods. In comparison to the
      52% responder rate (>50% seizure reduction) at ketogenic diet discontinuation,
      79% were now similarly improved (p = 0.0001). Ninety-six percent would recommend
      the ketogenic diet to others, yet only 54% would have started it before trying
      anticonvulsants. Lipids were normal (mean total cholesterol 158 mg/dl), despite
      most being abnormal while on the ketogenic diet. The mean Z scores for those
      younger than age 18 years were -1.28 for height and -0.79 for weight. In those 18
      years of age or older, the mean body mass index (BMI) was 22.2. DISCUSSION: This
      is the first study to report on the long-term effects of the ketogenic diet after
      discontinuation. The majority of subjects are currently doing well with regard to
      health and seizure control.

PMID- 20132288
TI  - Impact of severe epilepsy on development: recovery potential after successful
      early epilepsy surgery.
AB  - PURPOSE: Epilepsy surgery in young children with focal lesions offers a unique
      opportunity to study the impact of severe seizures on cognitive development
      during a period of maximal brain plasticity, if immediate control can be
      obtained. We studied 11 children with early refractory epilepsy (median onset,
      7.5 months) due to focal lesion who were rendered seizure-free after surgery
      performed before the age of 6 years. METHODS: The children were followed
      prospectively for a median of 5 years with serial neuropsychological assessments
      correlated with electroencephalography (EEG) and surgery-related variables.
      RESULTS: Short-term follow-up revealed rapid cognitive gains corresponding to
      cessation of intense and propagated epileptic activity [two with early
      catastrophic epilepsy; two with regression and continuous spike-waves during
      sleep (CSWS) or frontal seizures]; unchanged or slowed velocity of progress in
      six children (five with complex partial seizures and frontal or temporal cortical
      malformations). Longer-term follow-up showed stabilization of cognitive levels in
      the impaired range in most children and slow progress up to borderline level in
      two with initial gains. DISCUSSION: Cessation of epileptic activity after early
      surgery can be followed by substantial cognitive gains, but not in all children.
      In the short term, lack of catch-up may be explained by loss of retained function
      in the removed epileptogenic area; in the longer term, by decreased intellectual
      potential of genetic origin, irreversible epileptic damage to neural networks
      supporting cognitive functions, or reorganization plasticity after early focal
      lesions. Cognitive recovery has to be considered as a "bonus," which can be
      predicted in some specific circumstances.

PMID- 20132289
TI  - A ketogenic diet does not impair rat behavior or long-term potentiation.
AB  - The effect of the ketogenic diet on behavior and cognition is unclear. We
      addressed this issue in rats behaviorally and electrophysiologically.We fed
      postnatal day 21 rats a standard diet (SD), ketogenic diet (KD), or calorie
      restricted diet (CR) for 2-3 weeks. CR controlled for the slower weight gain
      experienced by KD-fed rats. We assessed behavioral performance with a locomotor
      activity and a conditioned fear test. To evaluate possible parallel effects of
      diet on synaptic function, we examined paired-pulse modulation (PPM) and long
      term potentiation (LTP) in the medial perforant path in vivo. KD-fed rats
      performed similarly to SD-fed rats on the behavioral tests and electrophysiologic
      assays. These data suggest that the KD does not alter behavioral performance or
      synaptic plasticity.

PMID- 20132290
TI  - Can BIS monitoring be used to assess the depth of propofol anesthesia in the
      treatment of refractory status epilepticus?
AB  - PURPOSE: Appropriate treatment of generalized convulsive refractory status
      epilepticus (RSE) requires general anesthesia in the intensive care unit (ICU)
      with continuous electroencephalography (cEEG) monitoring. During out of office
      hours and weekends, cEEG monitoring is not always available. The Bispectral Index
      (BIS) monitor can be used to assess the hypnotic component of general anesthesia.
      We conducted a study to evaluate the feasibility of using the BIS monitoring to
      assess the burst suppression (BS) pattern during propofol anesthesia in RSE.
      METHODS: Ten adult patients with RSE admitted to the ICU were monitored
      simultaneously with cEEG and BIS monitoring. We compared the BIS and suppression
      ratio (SR) values with the EEG burst suppression pattern when the depth of
      anesthesia was titrated to the BS level monitoring by cEEG. RESULTS: We found an
      excellent correlation between the cEEG burst rate per minute and the BIS (r2 =
      0.9; p< 0.001) and SR (r2 = -0.88; p < 0.001). The sensitivity and specificity of
      BIS score of 30 to detect BS in electroencephalography were 99% and 98%,
      respectively. The BIS monitor was not able to recognize regional epileptic
      activity and epileptic bursts during the BS pattern. DISCUSSION: The cEEG can be
      considered as the primary monitoring technique in the assessment of the depth of
      anesthesia in the treatment of RSE. If cEEG is not available, the BIS monitor can
      be used to guide the level of anesthesia, targeting BS in patients with RSE.

PMID- 20132291
TI  - Ictal hypoventilation contributes to cardiac arrhythmia and SUDEP: report on two
      deaths in video-EEG-monitored patients.
AB  - Sudden unexplained death in epilepsy (SUDEP) is a common cause of death in
      patients with epilepsy, with cardiorespiratory dysfunction and a primary
      cessation of cerebral function proposed as causes. We report two cases of SUDEP
      in patients with intractable temporal lobe epilepsy undergoing video-EEG
      (electroencephalography) telemetry at two centers. Both had secondarily
      generalized convulsions. EEG, electrocardiography (ECG), and respiratory changes
      in these two patients are reported herein. Ictal/postictal hypoventilation may
      contribute to SUDEP with the resulting hypoxemia and acidosis leading to failure
      of recovery of cortical function and eventual cardiac failure.

PMID- 20132292
TI  - Characteristics of a large population of patients with refractory epilepsy
      attending tertiary referral centers in Italy.
AB  - The characteristics of 1,124 consecutive adults and children with refractory
      epilepsy attending 11 tertiary referral centers in Italy were investigated at
      enrollment into a prospective observational study. Among 933 adults (age 16-86
      years), the most common syndromes were symptomatic (43.7%) and cryptogenic
      (39.0%) focal epilepsies, followed by idiopathic (8.1%) and
      cryptogenic/symptomatic generalized (6.2%) epilepsies. The most common syndrome
      among 191 children was symptomatic focal epilepsy (35.1%), followed by
      cryptogenic focal (18.8%), cryptogenic/symptomatic generalized (18.3%),
      undetermined whether focal or generalized (16.8%), and idiopathic generalized
      (7.3%). Primarily and secondarily generalized tonic-clonic seizures were reported
      in 27.8% of adults and 16.8% of children. The most commonly reported etiologies
      were mesial temporal sclerosis (8.0%) and disorders of cortical development
      (6.2%) in adults, and disorders of cortical development (14.7%) and
      nonprogressive encephalopathies (6.8%) in children. More than three-fourths of
      subjects in both age groups were on antiepileptic drug (AED) polytherapy.

PMID- 20132293
TI  - Sociocultural and psychological features of perceived stigma reported by people
      with epilepsy in Benin.
AB  - PURPOSE: Stigma is a major burden of epilepsy. In sub-Saharan Africa the few
      studies that addressed epilepsy stigma emphasize enacted, rather than perceived,
      stigma. This inattention may compromise clinical management and delay help
      seeking, thereby contributing to the treatment gap. We assessed perceived stigma
      and identified sociocultural and psychological factors explaining greater stigma
      among people with epilepsy (PWE) in Benin. METHODS: PWE included in this study
      were ascertained using a door-to-door survey in the general population in a
      Beninese rural area. We applied both qualitative and quantitative research
      methods to assess stigma and patient's experience and beliefs. An Explanatory
      Model Interview Catalogue (EMIC) and verbally administered questionnaires
      provided data for demographic, clinical, and sociocultural features.
      Sociocultural features were evaluated in terms of illness-related experience and
      sociocultural representations of epilepsy. Depression and anxiety were also
      screened. RESULTS: Eighty PWE were included. About 68.7% reported feeling
      stigmatized. Multivariate regression revealed that factors independently
      associated with perceived stigma were experience of social isolation (p < 0.001),
      experience of marital problems (p < 0.01), and presence of anxiety disorder (p <
      0.01). DISCUSSION: Perceived stigma is an important issue in epilepsy in Benin.
      Social factors seem to be more influential than sociocultural representation of
      epilepsy. Insofar as research is needed in other African countries to determine
      the nature and relevant features of stigma to improve treatment and control.

PMID- 20132294
TI  - WAG/Rij rats show a reduced expression of CB1 receptors in thalamic nuclei and
      respond to the CB1 receptor agonist, R(+)WIN55,212-2, with a reduced incidence of
      spike-wave discharges.
AB  - PURPOSE: Genetically epileptic WAG/Rij rats develop spontaneous absence-like
      seizures after 3 months of age. We used WAG/Rij rats to examine whether absence
      seizures are associated with changes in the expression of type-1 cannabinoid
      (CB1) receptors. METHODS: Receptor expression was examined by in situ
      hybridization and western blot analysis in various brain regions of
      "presymptomatic" 2-month old and "symptomatic" 8-month-old WAG/Rij rats relative
      to age-matched nonepileptic control rats. Furthermore, we examined whether
      pharmacologic activation of CB1 receptor affects absence seizures. We recorded
      spontaneous spike-wave discharges (SWDs) in 8-month old WAG/Rij rats systemically
      injected with the potent CB1 receptor agonist, R(+)WIN55,212-2 (3-12 mg/kg,
      s.c.), given alone or combined with the CB1 receptor antagonist/inverse agonist,
      AM251 (12 mg/kg, s.c.). RESULTS: Data showed a reduction of CB1 receptor mRNA and
      protein levels in the reticular thalamic nucleus, and a reduction in CB1 receptor
      protein levels in ventral basal thalamic nuclei of 8-month-old WAG/Rij rats, as
      compared with age-matched ACI control rats. In vivo, R(+)WIN55,212-2 caused a
      dose-dependent reduction in the frequency of SWDs in the first 3 h after the
      injection. This was followed by a late increase in the mean SWD duration, which
      suggests a biphasic modulation of SWDs by CB1 receptor agonists. Both effects
      were reversed or attenuated when R(+)WIN55,212-2 was combined with AM251.
      DISCUSSION: These data indicate that the development of absence seizures is
      associated with plastic modifications of CB1 receptors within the thalamic
      cortical-thalamic network, and raise the interesting possibility that CB1
      receptors are targeted by novel antiabsence drugs.

PMID- 20132295
TI  - Impaired gist memory in patients with temporal lobe epilepsy and hippocampal
      sclerosis.
AB  - PURPOSE: Temporal lobe epilepsy (TLE) is the most common focal epilepsy and
      frequently causes memory problems. It is often associated with hippocampal
      sclerosis (HS) and is useful in exploring memory functions. We aimed to examine
      the effect of restricted hippocampal lesions on gist memory function in patients
      with TLE. METHODS: Forty-five patients with TLE and HS (16 left, 15 right, and 14
      bilateral lesions) and 22 control subjects were recruited. Patients with magnetic
      resonance imaging (MRI) or electroencephalography (EEG) evidence of extratemporal
      lesions were excluded. All participants performed a gist-based recognition task
      following the Deese-Roediger-McDermott paradigm and were tested for verbal IQ and
      memory functions. We conducted hippocampal volumetry on MRI of all the
      participants. RESULTS: Patients showed multidomain memory impairments. Gist
      memory was impaired in patients with bilateral HS and probably in patients with
      right HS. Hippocampal volumetry supported such findings that total volume of
      hippocampi and volume of right hippocampus correlated positively with gist memory
      function. DISCUSSION: HS has a dose effect and a probable right dominance effect
      on gist memory; good item memory supports gist memory performance; and a
      disproportionate deficit was noted in tasks with high relational demand but not
      in tasks with simple association. We should develop memory skills for patients
      with TLE by enhancing performance of gist memory related to simple association
      task.

PMID- 20132296
TI  - Altered white matter integrity in temporal lobe epilepsy: association with
      cognitive and clinical profiles.
AB  - PURPOSE: Diffusion tensor imaging (DTI) studies have reported substantial white
      matter abnormalities in patients with temporal lobe epilepsy (TLE). However,
      limited data exist regarding the extent of white matter tract abnormalities,
      cognitive effects of these abnormalities, and relationship to clinical factors.
      The current study examined these issues in subjects with chronic TLE. METHODS:
      DTI data were obtained in 12 TLE subjects and 10 age-matched healthy controls.
      Voxel-wise statistical analysis of fractional anisotropy (FA) was carried out
      using tract-based spatial statistics (TBSS). White matter integrity was
      correlated with cognitive performance and epilepsy-related clinical parameters.
      RESULTS: Subjects with TLE, as compared to healthy controls, demonstrated four
      clusters of reduced FA, in anterior temporal lobe, mesial temporal lobe, and
      cerebellum ipsilateral, as well as frontoparietal lobe contralateral to the side
      of seizure onset. Mean FA was positively correlated with delayed memory, in
      anterior temporal lobe; and immediate memory, in mesial temporal lobe. Lower FA
      values in the posterior region of corpus callosum were related to earlier age of
      seizure onset. CONCLUSION: TLE is associated with widespread disturbances in
      white matter tracts and these changes have important cognitive and clinical
      consequences.

PMID- 20132297
TI  - Impaired maturation of cortical GABA(A) receptor expression in pediatric
      epilepsy.
AB  - PURPOSE: Expression of the protein subunits that make up the gamma-aminobutyric
      acid (GABA)(A) receptor pentamer is known to change during postnatal brain
      development in animal models. In the present study, analysis of cortical GABA(A)
      subunit expression was performed in control human tissue obtained from infancy
      through adolescence, and was compared to that from similarly aged children with
      intractable focal epilepsy. METHODS: Twenty frozen pediatric control and 25
      epileptic neocortical specimens were collected. The membrane fractions were
      isolated and subjected to quantitative western blot analysis. Subunit expression
      was correlated with clinical factors including age, pathology, and medication
      exposure. RESULTS: In control cortical samples, alpha1 and gamma2 GABA(A)
      receptor subunits exhibited low expression in infancy, which increased over the
      first several years of life and then stabilized through adolescence. In contrast,
      alpha4 subunit expression was higher in infants than in older children. The level
      of the chloride transporter KCC2 increased markedly with age, whereas that of
      NKCC1 decreased. These patterns were absent in the children with epilepsy, both
      in those with focal cortical dysplasia and in those with cortical gliosis.
      Although there was marked variability in GABA(A) receptor subunit expression
      among the children with epilepsy, identifiable patterns of subunit expression
      were found in each individual child. DISCUSSION: Maturation of cortical GABA(A)
      receptor subunit expression continues over the first several years of postnatal
      human development. Intractable focal epilepsy in children is associated with
      disruption of this normal developmental pattern. These findings have significant
      implications for the treatment of children with medications that modulate GABA(A)
      receptor function.

PMID- 20132298
TI  - Safety profile of oxcarbazepine: results from a prescription-event monitoring
      study.
AB  - PURPOSE: To monitor safety of oxcarbazepine, prescribed in primary care in
      England, using prescription-event monitoring (PEM). METHODS: Postmarketing
      surveillance using observational cohort technique of PEM. Exposure data were
      obtained from dispensed British National Health Service prescriptions issued by
      general practitioners (GPs) March 2000-July 2003. Demographic, drug utilization,
      and clinical event data were collected from questionnaires posted to GPs at least
      6 months after first prescription date for each patient. Incidence densities
      (IDs) (number of first reports per 1,000 patient-months of treatment) were
      calculated and differences for events reported in month 1 (ID(1)) and months 2-6
      (ID(2-6)) (99% confidence intervals) were examined for changes in event rates.
      Follow-up and causality assessment of medically significant events were
      undertaken. RESULTS: The cohort comprised 2,243 patients [mean age 40.4 years;
      range 2-99 years; standard deviation (SD) 18.8; 46.3% (n = 1,038) male]. Most
      frequently reported primary indications were epilepsy, convulsion (n = 1,111;
      49.5%, n = 209; 9.3%, respectively). GPs recorded 932 reasons for stopping
      medication in 698 (31.1%) patients; most frequent clinical reason
      "drowsiness/sedation" (n = 57; 2.5% of cohort). Clinical events (excluding
      indication) associated with starting treatment (lower 99% CI > 0) included:
      "drowsiness/sedation" (ID(1)-ID(2-6) = 14.2), "nausea/vomiting" (ID(1)-ID(2-6) =
      13.0), and dizziness (ID(1)-ID(2-6) = 11.6). Events followed up and assessed as
      probably related to oxcarbazepine use included rash (7 of 11) and hyponatremia
      (15 of 38). DISCUSSION: There were no serious adverse drug reactions reported
      during this study. Results of the study should be taken in context with other
      epidemiologic studies.

PMID- 20132299
TI  - 100 years of Epilepsia: landmark papers and their influence in neuropsychology
      and neuropsychiatry.
AB  - As part of the 2009 International League Against Epilepsy (ILAE) Centenary
      Celebration, a special symposium was dedicated to Epilepsia (100 Years of
      Epilepsia: Landmark Papers and Their Influence). The Associate Editors were asked
      to identify a particularly salient and meaningful paper in their areas of
      expertise. From the content areas of neuropsychology and neuropsychiatry two very
      interesting papers were identified using quite different ascertainment
      techniques. One paper addressed the problem of psychosis in temporal lobe
      epilepsy, whereas the other represents the first paper to appear in Epilepsia
      presenting quantitative assessment of cognitive status in epilepsy. These two
      papers are reviewed in detail and placed in historical context.

PMID- 20132300
TI  - Evaluation of the genetic basis of phenotypic heterogeneity in north Indian
      patients with thalassemia major.
AB  - OBJECTIVES: To assess the molecular basis of phenotypic heterogeneity in north
      Indian patients with thalassemia major (TM). METHODS: To determine the clinical
      severity, 130 patients of TM were studied for the age of first presentation and
      frequency of blood transfusion. The type of beta mutations, Xmn-1(G)gamma
      polymorphism and G6PD Mediterranean mutation was characterized. Analysis of the
      phenotypic presentation and the genotype was performed. RESULTS: Majority (83.8%)
      presented before 1 year of age (mean 8.8 months). The caste distribution showed
      41.6% were Aroras and 32.3% were migrants from Pakistan. IVS1-5(G-->C) was
      commonest (32.7%) and the common five Indian mutations comprised of 88.4% of
      alleles. The mean age of presentation with IVS1-5(G-->C), Fr 8/9, (+G) 619-bp del
      and IVS1-1(G-->T) homozygosity was 4.3, 6, 3.4 and 9.1 months respectively. Xmn
      1(G)gamma status showed -/- in 66.9%, +/- in 26.1% and +/+ in 6.9% patients. Xmn
      1(G)gamma-/- presented before 1 year of age. The mean age of presentation with
      +/+ was 18.3 months. Six hemizygous boys and one heterozygous girl with G6PD
      Mediterranean were found (prevalence 5.3%). Eight patients could be reclassified
      as thalassemia intermedia on follow up. CONCLUSIONS: This study showed that
      majority of TM in north India present before 1 year of age and homozygous 619-bp
      deletion presents the earliest. The presence of Xmn-1(G)gamma polymorphism delays
      the presentation, is associated with the IVS 1-1 (G-->T) and shows variable
      improvement with hydroxyurea therapy. Based on the results of genotyping,
      reevaluation of patients can improve the outcome in a few patients.

PMID- 20132301
TI  - Whole brain radiation alone produces favourable outcomes for AIDS-related primary
      central nervous system lymphoma in the HAART era.
AB  - Primary central nervous system lymphoma (PCNSL) related to acquired
      immunodeficiency syndrome (AIDS) is a lethal disorder, but the recent application
      of highly active antiretroviral therapy (HAART) has significantly improved
      prognosis. This retrospective cohort study of AIDS-related PCNSL examined the
      actual clinical outcomes and prognostic variables affecting overall survival (OS)
      in the HAART era. Twenty-three newly diagnosed AIDS-related PCNSL at 12 regional
      centre hospitals for HIV/AIDS in Japan between 2002 and 2008 were consecutively
      enrolled. The estimated 3-yr OS rate of the entire cohort was 64% (95%CI, 41.0
      80.3%). Whole brain radiation therapy (WBRT) had an independent positive impact
      on survival (WBRT >or=30 Gy vs. others, P = 0.02). Nine of 10 patients with a
      good performance status (PS) (0-2) remained alive with complete response, whereas
      10 (77%) of 13 of those with a poor PS (3-4) died mostly after a short period.
      The estimated 3-yr OS rate of the groups with a good and poor PS was 100% and 38%
      (95%CI, 14-63%), respectively (P = 0.01). Leukoencephalopathy (grade >or= 2)
      developed in 21% of those that survived more than 12 months after radiation. The
      patients receiving a curative intent radiation dose (>or=30 Gy) of WBRT achieved
      prolonged survival while maintaining a good quality of life in the HAART era,
      especially among patients with a favourable PS.

PMID- 20132302
TI  - Two cases of agranulocytosis associated with cocaine use: is this phenomenon
      becoming more prevalent?

PMID- 20132303
TI  - Significant change in ZAP-70 expression during the course of chronic lymphocytic
      leukemia.
AB  - INTRODUCTION: It is widely accepted that expression of ZAP-70 in chronic
      lymphocytic leukemia (CLL) remains stable in time. However, data supporting this
      notion are surprisingly scarce. Therefore, we assessed expression of ZAP-70 in
      serial samples taken during the course of the disease. PATIENTS AND METHODS: We
      studied 44 patients with CLL diagnosed according to NCI-WG criteria (34 men, 10
      women, median age 62, range, 36-81). A total of 104 samples were examined; all
      patients had at least two measurements. Median interval between the first and the
      second sample was 13 months (range, 2-36). ZAP-70 expression was detected by flow
      cytometry using phycoerythrin-conjugated monoclonal antibody clone 1E7.2 and
      negative isotype control. Twenty percent of positive cells were considered as the
      threshold of positivity. RESULTS: Significant change in ZAP-70 expression (i.e.
      from positivity to negativity and vice versa) was detected in 15/44 patients
      (34%). Interestingly, 7/8 patients whose ZAP-70 expression converted to
      positivity had unmutated IgVH genes. In addition, the conversion was accompanied
      by clinical progression or relapse in all but one patient. On the other hand, 5/7
      patients with loss of ZAP-70 had stable clinical course. One patient became ZAP
      70-negative during treatment with prednisone for autoimmune hemolytic anemia.
      CONCLUSIONS: In contrast to commonly accepted opinion, significant change in ZAP
      70 expression in time was detected in a substantial proportion of our patients
      with CLL. While the conversion to ZAP-70 negativity was found predominantly in
      patients with stable disease, change to positivity was typical in patients with
      unmutated IgVH genes at the time of progression or relapse. Based on our pilot
      results, repeated assessment of ZAP-70 expression might be especially useful at
      the time of progression or relapse in patients who were initially ZAP-70
      negative.

PMID- 20132304
TI  - Molecular characteristics of community-acquired, methicillin-resistant
      Staphylococcus aureus isolated from Chinese children.
AB  - The aim of this study was to investigate the molecular characteristics of
      community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA)
      isolates from Chinese children. Ninety-nine isolates were collected from eight
      hospitals, and analyzed by multilocus sequence typing, staphylococcal chromosomal
      cassette mec (SCCmec) type, and spa typing. The Panton-Valentine leukocidin (PVL)
      gene was also detected. Overall, 14 sequence types (STs) were obtained, and ST59
      (58.6%) was found to be the most prevalent, followed by ST1 (8%) and ST338 (8%).
      We also first registered the new ST1409. SCCmec type IV was the most predominant
      type at 67.7%, followed by SCCmec type V at 32.3%. SCCmec subtypes IVa, IVc, and
      IVg were found among the SCCmec type IV strains. Twenty-one spa types were also
      identified. Four new spa types were found by synchronization with the Ridom
      SpaServer and referring to the website (http://www.SeqNet.org). ST59-MRSA-IVa
      with t437 accounted for 40.4% of occurrences, making it the most prevalent clone.
      The prevalence of PVL genes was 58.6%, and multidrug resistance was observed in
      95% of all isolates. This result indicates that CA-MRSA isolates in Chinese
      children are largely associated with the ST59-MRSA-IV clone, and that the
      predominant clones of CA-MRSA are spread all over the country.

PMID- 20132305
TI  - Autoactivation of the AggR regulator of enteroaggregative Escherichia coli in
      vitro and in vivo.
AB  - Enteroaggregative Escherichia coli (EAEC) causes diarrhea in diverse populations
      worldwide. The AraC-like regulator AggR is a key virulence regulator in EAEC.
      AggR-regulated genes include those encoding the Aggregative Adherence Fimbria,
      the dispersin protein, and a type VI secretion system. This study characterizes
      the regulation of the aggR promoter (P(aggR)). Using primer extension analysis,
      the transcriptional start site of the aggR promoter was located 40 nucleotides
      upstream of the translational start. P(aggR) was found to be autoregulated and
      DNA footprinting revealed the presence of two AggR-binding sites: one upstream of
      the transcriptional start site and one downstream. Additionally, P(aggR) was
      found to be positively regulated by the DNA-binding protein FIS and negatively
      regulated by the global regulator H-NS. To further understand this complex
      regulation scheme, a bacterial luciferase reporter system was used with a mouse
      model of EAEC colonization. This allowed for the in vivo measurement of P(aggR),
      P(fis), and P(hns) activity. EAEC present in the mouse intestine possessed
      relatively high levels of P(fis) and P(aggR) activity and a low level of P(hns)
      when compared with in vitro experiments. The data provide significant insights
      into the regulation cascade leading to aggR expression in the mammalian intestine
      during EAEC infection.

PMID- 20132306
TI  - Class 1 integrons in benthic bacterial communities: abundance, association with
      Tn402-like transposition modules and evidence for coselection with heavy-metal
      resistance.
AB  - The integron/gene cassette system contributes to lateral gene transfer of genetic
      information in bacterial communities, with gene cassette-encoded proteins
      potentially playing an important role in adaptation to stress. Class 1 integrons
      are a particularly important class as they themselves seem to be broadly
      disseminated among the Proteobacteria and have an established role in the spread
      of antibiotic resistance genes. The abundance and structure of class 1 integrons
      in freshwater sediment bacterial communities was assessed through sampling of 30
      spatially distinct sites encompassing different substrate and catchment types
      from the Greater Melbourne Area of Victoria, Australia. Real-time PCR was used to
      demonstrate that the abundance of intI1 was increased as a result of ecosystem
      perturbation, indicated by classification of sample locations based on the
      catchment type and a strong positive correlation with the first principal
      component factor score, comprised primarily of the heavy metals zinc, mercury,
      lead and copper. Additionally, the abundance of intI1 at sites located downstream
      from treated sewage outputs was associated with the percentage contribution of
      the discharge to the basal flow rate. Characterization of class 1 integrons in
      bacteria cultured from selected sediment samples identified an association with
      complete Tn402-like transposition modules, and the potential for coselection of
      heavy-metal and antibiotic resistance mechanisms in benthic environments.

PMID- 20132307
TI  - Esterase activity of Bordetella pertussis CyaC-acyltransferase against synthetic
      substrates: implications for catalytic mechanism in vivo.
AB  - Adenylate cyclase-hemolysin toxin (CyaA) produced from the human respiratory
      tract pathogen Bordetella pertussis requires fatty-acyl modification by CyaC
      acyltransferase to become an active toxin. Previously, the recombinant CyaA pore
      forming (CyaA-PF) fragment expressed in Escherichia coli was shown to be
      hemolytically active upon palmitoylation in vivo by cosynthesized CyaC. Here, the
      21-kDa CyaC enzyme separately expressed in E. coli as an inclusion body was
      solubilized in 8 M urea and successfully refolded into an enzymatically active
      monomer. In addition to the capability of activating CyaA-PF in vitro, CyaC
      showed esterase activity against p-nitrophenyl acetate (pNPA) and p-nitrophenyl
      palmitate (pNPP), with preferential hydrolysis toward pNPP when compared with
      chymotrypsin. A homology-based CyaC structure suggested a conceivable role of a
      catalytic triad including Ser(30), His(33) and Tyr(66) in substrate catalysis.
      Alanine substitutions of these individual residues caused a drastic decrease in
      specific activities of all three mutant enzymes (S30A, H33A and Y66A) toward
      pNPP, signifying that CyaC-acyltransferase shares a similar mechanism of
      hydrolysis with a serine esterase in which Ser(30) is part of the catalytic
      triad.

PMID- 20132309
TI  - Virulence analysis and gene expression profiling of the pigment-deficient mutant
      of Xanthomonas oryzae pathovar oryzae.
AB  - Xanthomonas oryzae pathovar oryzae (Xoo) causes bacterial blight disease in rice
      (Oryza sativa L.). For a study of function, we constructed a random insertion
      mutant library of Xoo using a Tn5 transposon and isolated the mutant strain (M11;
      aroK::Tn5) that had extremely low pigment production. In addition, M11 had
      decreased virulence against the susceptible rice cultivar IR24. Thermal
      asymmetric interlaced-PCR and sequence analysis of M11 revealed that the
      transposon was inserted into the aroK gene (which encodes a shikimate kinase). To
      investigate the expression patterns of the pigment- and virulence-deficient
      mutant, DNA microarray analysis was performed. In addition, reverse transcriptase
      PCR was performed to confirm the expression levels of several genes, including
      the aro genes of the aroK mutant. Our findings reveal that several crucial genes
      for virulence, including cellulase and hypersensitive response and pathogenicity
      (hrp) genes, were regulated by mutations in the aroK gene.

PMID- 20132311
TI  - A thioredoxin reductase-like protein from the thermophile, Thermus scotoductus SA
      01, displaying iron reductase activity.
AB  - The transition metal iron is an important element for the sustenance of life--it
      can function either as an electron acceptor or as a donor and serves as a
      cofactor in many enzymes activities. The cytoplasmic NAD(P)H-dependent ferric
      reductase in Thermus scotoductus SA-01 shares high sequence and structural
      similarity to prokaryotic thioredoxin reductases. Here we report the sequence of
      the ferric reductase (which is typically annotated as a thioredoxin reductase
      like protein) and a comparative kinetic study with the thioredoxin reductase from
      SA-01. Structurally, the most noteworthy difference, immediately apparent from
      the protein sequence, is the absence of the disulphide redox centre in the ferric
      reductase. This is the first report relating the attributes of such a redox
      protein to its ability to reduce a ferric substrate.

PMID- 20132312
TI  - Genome analysis of microorganisms living in amoebae reveals a melting pot of
      evolution.
AB  - Amoebae-resistant microorganisms exhibit a specific lifestyle. Unlike allopatric
      specialized intracellular pathogens, they have not specialized because they
      infect the amoebae via amoebal attack and present a sympatric lifestyle with
      species from different phyla. In this review, we compare the genomes from
      bacteria (Legionella pneumophila, Legionella drancourtii,
      Candidatus'Protochlamydia amoebophila,' Rickettsia bellii,
      Candidatus'Amoebophilus asiaticus') and a virus (mimivirus) that multiply
      naturally in amoebae. The objective is to highlight the genomic traits
      characterizing these microorganisms and their niche by comparison with other
      specialized pathogens. The genome of intra-amoebal microorganisms is
      significantly larger than that of their relatives, contradicting the genome
      reduction theory mostly accepted for intracellular pathogens. This is probably
      due to the fact that they are not specialized and therefore maintain their genome
      size. Moreover, the presence of many horizontally transferred genes and mobilomes
      in their genomes suggests that these microorganisms acquired genetic material
      from their neighbors and amoebal host, thus increasing their genome size.
      Important features involved in gene transfer and pathogenicity were thus
      acquired. These characteristics suggest that amoebae constitute a gene melting
      pot, allowing diverse microorganisms to evolve by the same pathway characterized
      by gene acquisition, and then either adapt to the intra-amoebal lifestyle or
      create new pathogens.

PMID- 20132313
TI  - Inhibitory effects of gallic acid ester derivatives on Saccharomyces cerevisiae
      multidrug resistance protein Pdr5p.
AB  - Overexpression of the Saccharomyces cerevisiae ABC transporter Pdr5p confers
      resistance to a range of structurally unrelated xenobiotics. This property allows
      Pdr5p to be used as a target for novel multidrug resistance reversal reagents or
      chemosensitizers. Herein, we report the effects of gallic acid derivatives with
      substitutions either on the ester moiety or in the benzene ring on the activity
      of Pdr5p. Compounds with a longer side chain (8-16 carbons) resulted in greater
      inhibition of Pdr5p ATPase. Derivatives with side chains of 8-12 carbons that
      retained hydroxyl groups on the benzene ring extensively inhibited Pdr5p ATPase
      activity. These compounds almost completely inhibited the efflux of the Pdr5p
      fluorescent substrate Rhodamine 6G and at 25 muM chemosensitized the Pdr5p
      overexpressing strain AD124567 to fluconazole (0.4 mg mL(-1)). Gallic acid
      derivatives may be a new class of Pdr5p inhibitors.

PMID- 20132314
TI  - Association of dopamine- and serotonin-related genes with canine aggression.
AB  - Human-directed canine aggression was studied using 50 aggressive and 81 non
      aggressive dogs. We examined 62 single nucleotide polymorphisms (SNPs) occurring
      in or in the close vicinity of 16 neurotransmitter-related genes. Allelic
      associations with aggression were identified for DRD1, HTR1D, HTR2C and SLC6A1.
      Risk or protective haplotypes for aggressive behaviour based on 2-5 SNPs were
      identified. The frequency of aggressive dogs varied significantly between the
      haplotypes within loci and the odds ratios of aggression in dogs with risk
      haplotypes compared with protective haplotypes varied from 4.4 (HTR2C) to 9.0
      (SLC6A1). A risk haplotype across the neurotransmitter receptor gene HTR1D
      harboured a non-synonymous SNP with a potential effect on protein function. We
      identified no haplotypes in complete association with the recorded phenotypes,
      supporting a complex inheritance of aggression.

PMID- 20132315
TI  - Association between genetic variants of the metabotropic glutamate receptor 3
      (GRM3) and cognitive set shifting in healthy individuals.
AB  - Set-shifting and maintenance are complex cognitive processes, which are often
      impaired in schizophrenia. The genetic basis of these processes is poorly
      understood. We aimed to investigate the association between genetic variants of
      the metabotropic glutamate receptor 3 (GRM3) and cognitive set-shifting in
      healthy individuals. The relationship between 14 selected single nucleotide
      polymorphisms (SNPs) of the GRM3 gene and cognitive set-shifting as measured by
      perseverative errors using the modified card sorting test (MCST) was analysed in
      a sample of N = 98 young healthy individuals (mean age in years: 22.7 +/- 0.19).
      Results show that SNP rs17676277 is related to the performance on the MCST.
      Subjects with the TT genotype showed significantly less perseverative errors as
      compared with the AA (P = 0.025) and AT (P = 0.0005) and combined AA/AT genotypes
      (P = 0.0005). Haplotype analyses suggest the involvement of various SNPs of the
      GRM3 gene in perseverative error processing in a dominant model of inheritance.
      The findings strongly suggest that the genetic variation (rs17676277 and three
      haplotypes) in the metabotropic GRM3 is related to cognitive set-shifting in
      healthy individuals independent of working memory. However, because of a
      relatively small sample size for a genetic association study, the present results
      are tentative and require replication.

PMID- 20132316
TI  - BDNF moderates early environmental risk factors for anxiety in mouse.
AB  - Anxiety is known to be influenced by both adverse childhood experiences and
      genetic susceptibility factors. A polymorphism in the brain-derived neurotrophic
      factor (BDNF) gene modulates the association between adverse early experiences
      and risk for anxiety and depression in adulthood. An animal model of this gene-by
      environment risk factor is lacking. Using two different early environmental
      manipulations, we found that a heterozygous null mutation in the mouse BDNF gene
      moderated the long-term effect of maternal care on innate anxiety behavior.
      Although changes in maternal care were associated with mild changes in anxiety in
      wild-type mice, this effect was magnified in heterozygous null BDNF mice with
      high- and low-maternal care associated with low and high levels, respectively, of
      avoidance behavior as measured in the open field and elevated plus maze tests.
      These data argue for an increased sensitivity to early environmental influences
      of mice with reduced BDNF function and support the important role of this
      neurotrophic factor in the developmental plasticity of brain circuits controlling
      anxiety.

PMID- 20132317
TI  - Association between AKT1 but not AKTIP genetic variants and increased risk for
      suicidal behavior in bipolar patients.
AB  - We tested the hypothesis that the presence of AKT1 and AKTIP polymorphisms,
      target genes that encode key proteins in the signaling of dopaminergic and
      serotonergic systems, is associated with suicidal behavior in bipolar patients.
      The subjects were 273 patients diagnosed with bipolar disorder I or II (age =
      41.4 +/- 12.9). TaqMan single-nucleotide polymorphism genotyping assays (AKT1:
      rs2494731, rs3803304, rs3730358, rs10149779, rs2494746, rs1130214 and rs249878;
      AKTIP: rs9302648 and rs7189819) were used. We found that the AKT1 marker showed
      an association with suicide attempts (rs1130214, P < 0.05) and attempted violent
      attacks (rs2494746, P < 0.05). One out of the seven tested markers of AKT1
      attained significant genotype association with violent attempt (rs2494731; P <
      0.05). A significant association was detected in the AKT1 haplotype test. We did
      not observe an association between suicidal behavior and AKTIP variants and also
      did not find an interaction between AKTIP and AKT1 polymorphisms. In addition, we
      found that demographic and clinical data are associated with lifetime history of
      suicide attempts. Our data suggest that demographic and clinical characteristics
      and AKT1 single markers and haplotypes, but not AKTIP polymorphisms or
      interactions between AKT1 and AKTIP, are associated with increased risk for
      suicidal behavior in bipolar patients.

PMID- 20132318
TI  - The structure of innate vocalizations in Foxp2-deficient mouse pups.
AB  - Heterozygous mutations of the human FOXP2 gene are implicated in a severe speech
      and language disorder. Aetiological mutations of murine Foxp2 yield abnormal
      synaptic plasticity and impaired motor-skill learning in mutant mice, while
      knockdown of the avian orthologue in songbirds interferes with auditory-guided
      vocal learning. Here, we investigate influences of two distinct Foxp2 point
      mutations on vocalizations of 4-day-old mouse pups (Mus musculus). The R552H
      missense mutation is identical to that causing speech and language deficits in a
      large well-studied human family, while the S321X nonsense mutation represents a
      null allele that does not produce Foxp2 protein. We ask whether vocalizations,
      based solely on innate mechanisms of production, are affected by these
      alternative Foxp2 mutations. Sound recordings were taken in two different
      situations: isolation and distress, eliciting a range of call types, including
      broadband vocalizations of varying noise content, ultrasonic whistles and clicks.
      Sound production rates and several acoustic parameters showed that, despite
      absence of functional Foxp2, homozygous mutants could vocalize all types of
      sounds in a normal temporal pattern, but only at comparably low intensities. We
      suggest that altered vocal output of these homozygotes may be secondary to
      developmental delays and somatic weakness. Heterozygous mutants did not differ
      from wild-types in any of the measures that we studied (R552H ) or in only a few
      (S321X ), which were in the range of differences routinely observed for different
      mouse strains. Thus, Foxp2 is not essential for the innate production of
      emotional vocalizations with largely normal acoustic properties by mouse pups.

PMID- 20132319
TI  - alpha8-integrins are required for hippocampal long-term potentiation but not for
      hippocampal-dependent learning.
AB  - Integrins are heterodimeric transmembrane cell adhesion receptors that are
      essential for a wide range of biological functions via cell-matrix and cell-cell
      interactions. Recent studies have provided evidence that some of the subunits in
      the integrin family are involved in synaptic and behavioral plasticity. To
      further understand the role of integrins in the mammalian central nervous system,
      we generated a postnatal forebrain and excitatory neuron-specific knockout of
      alpha8-integrin in the mouse. Behavioral studies showed that the mutant mice are
      normal in multiple hippocampal-dependent learning tasks, including a T-maze, non
      match-to-place working memory task for which other integrin subunits like alpha3-
      and beta1-integrin are required. In contrast, mice mutant for alpha8-integrin
      exhibited a specific impairment of long-term potentiation (LTP) at Schaffer
      collateral-CA1 synapses, whereas basal synaptic transmission, paired-pulse
      facilitation and long-term depression (LTD) remained unaffected. Because LTP is
      also impaired in the absence of alpha3-integrin, our results indicate that
      multiple integrin molecules are required for the normal expression of LTP, and
      different integrins display distinct roles in behavioral and neurophysiological
      processes like synaptic plasticity.

PMID- 20132320
TI  - Genetic evidence for Dnmt3a-dependent imprinting during oocyte growth obtained by
      conditional knockout with Zp3-Cre and complete exclusion of Dnmt3b by chimera
      formation.
AB  - In the male and female germ-lines of mice, both of the two de novo DNA
      methyltransferases Dnmt3a and Dnmt3b are expressed. By the conditional knockout
      experiments using the Tnap-Cre gene, we previously showed that deletion of Dnmt3a
      in primordial germ cells disrupts paternal and maternal imprinting, however,
      Dnmt3b mutants did not show any defect. Here, we have knocked out Dnmt3a after
      birth in growing oocytes by using the Zp3-Cre gene and obtained genetic evidence
      that de novo methylation by Dnmt3a during the oocyte growth stage is
      indispensable for maternal imprinting. We also carried out DNA methylation
      analysis in the mutant oocytes and embryos and found that hypomethylation of
      imprinted genes in Dnmt3a-deficient oocytes was directly inherited to the
      embryos, but repetitive elements were re-methylated during development.
      Furthermore, we show that Dnmt3b-deficient cells can contribute to the male and
      female germ-lines in chimeric mice and can produce normal progeny, establishing
      that Dnmt3b is dispensable for mouse gametogenesis and imprinting. Finally, Dnmt3
      related protein Dnmt3L is not only essential for methylation of imprinted genes
      but also enhances de novo methylation of repetitive elements in growing oocytes. 

PMID- 20132321
TI  - Citation and acceptance of the 2009 M. King Hubbert Award.

PMID- 20132322
TI  - Measuring the permeability of open-framework gravel.
AB  - Open-framework gravel has permeability, k, above the measurement range of most
      laboratory constant-head permeameters because the head difference across the
      length of conventional permeameters is too small to be measured. Here we
      addressed the challenge of measuring the high k by using a 3 m long permeameter.
      The head difference over this length was of the order of 10(-2) to 10(-3) m,
      which we could measure to the nearest 10(-5) m. We collected data over the range
      of linear, laminar flow to nonlinear, laminar flow to verify that k was measured
      using data collected within the Darcian regime. We measured k between 4000 and
      100,000 Darcies among experiments using different sediments.

PMID- 20132323
TI  - Linking MODFLOW with an agent-based land-use model to support decision making.
AB  - The U.S. Geological Survey numerical groundwater flow model, MODFLOW, was
      integrated with an agent-based land-use model to yield a simulator for
      environmental planning studies. Ultimately, this integrated simulator will be
      used as a means to organize information, illustrate potential system responses,
      and facilitate communication within a participatory modeling framework. Initial
      results show the potential system response to different zoning policy scenarios
      in terms of the spatial patterns of development, which is referred to as urban
      form, and consequent impacts on groundwater levels. These results illustrate how
      the integrated simulator is capable of representing the complexity of the system.
      From a groundwater modeling perspective, the most important aspect of the
      integration is that the simulator generates stresses on the groundwater system
      within the simulation in contrast to the traditional approach that requires the
      user to specify the stresses through time.

PMID- 20132324
TI  - A hybrid finite-difference and analytic element groundwater model.
AB  - Regional finite-difference models tend to have large cell sizes, often on the
      order of 1-2 km on a side. Although the regional flow patterns in deeper
      formations may be adequately represented by such a model, the intricate surface
      water and groundwater interactions in the shallower layers are not. Several
      stream reaches and nearby wells may occur in a single cell, precluding any
      meaningful modeling of the surface water and groundwater interactions between the
      individual features. We propose to replace the upper MODFLOW layer or layers, in
      which the surface water and groundwater interactions occur, by an analytic
      element model (GFLOW) that does not employ a model grid; instead, it represents
      wells and surface waters directly by the use of point-sinks and line-sinks. For
      many practical cases it suffices to provide GFLOW with the vertical leakage rates
      calculated in the original coarse MODFLOW model in order to obtain a good
      representation of surface water and groundwater interactions. However, when the
      combined transmissivities in the deeper (MODFLOW) layers dominate, the accuracy
      of the GFLOW solution diminishes. For those cases, an iterative coupling
      procedure, whereby the leakages between the GFLOW and MODFLOW model are updated,
      appreciably improves the overall solution, albeit at considerable computational
      cost. The coupled GFLOW-MODFLOW model is applicable to relatively large areas, in
      many cases to the entire model domain, thus forming an attractive alternative to
      local grid refinement or inset models.

PMID- 20132325
TI  - Evaluating MT3DMS for heat transport simulation of closed geothermal systems.
AB  - Owing to the mathematical similarities between heat and mass transport, the multi
      species transport model MT3DMS should be able to simulate heat transport if the
      effects of buoyancy and changes in viscosity are small. Although in several
      studies solute models have been successfully applied to simulate heat transport,
      these studies failed to provide any rigorous test of this approach. In the
      current study, we carefully evaluate simulations of a single borehole ground
      source heat pump (GSHP) system in three scenarios: a pure conduction situation,
      an intermediate case, and a convection-dominated case. Two evaluation approaches
      are employed: first, MT3DMS heat transport results are compared with analytical
      solutions. Second, simulations by MT3DMS, which is finite difference, are
      compared with those by the finite element code FEFLOW and the finite difference
      code SEAWAT. Both FEFLOW and SEAWAT are designed to simulate heat flow. For each
      comparison, the computed results are examined based on residual errors. MT3DMS
      and the analytical solutions compare satisfactorily. MT3DMS and SEAWAT results
      show very good agreement for all cases. MT3DMS and FEFLOW two-dimensional (2D)
      and three-dimensional (3D) results show good to very good agreement, except that
      in 3D there is somewhat deteriorated agreement close to the heat source where the
      difference in numerical methods is thought to influence the solution. The results
      suggest that MT3DMS can be successfully applied to simulate GSHP systems, and
      likely other systems with similar temperature ranges and gradients in saturated
      porous media.

PMID- 20132326
TI  - Taking account of "unknown unknowns".

PMID- 20132327
TI  - Quantifying data worth toward reducing predictive uncertainty.
AB  - The present study demonstrates a methodology for optimization of environmental
      data acquisition. Based on the premise that the worth of data increases in
      proportion to its ability to reduce the uncertainty of key model predictions, the
      methodology can be used to compare the worth of different data types, gathered at
      different locations within study areas of arbitrary complexity. The method is
      applied to a hypothetical nonlinear, variable density numerical model of salt and
      heat transport. The relative utilities of temperature and concentration
      measurements at different locations within the model domain are assessed in terms
      of their ability to reduce the uncertainty associated with predictions of
      movement of the salt water interface in response to a decrease in fresh water
      recharge. In order to test the sensitivity of the method to nonlinear model
      behavior, analyses were repeated for multiple realizations of system properties.
      Rankings of observation worth were similar for all realizations, indicating
      robust performance of the methodology when employed in conjunction with a highly
      nonlinear model. The analysis showed that while concentration and temperature
      measurements can both aid in the prediction of interface movement, concentration
      measurements, especially when taken in proximity to the interface at locations
      where the interface is expected to move, are of greater worth than temperature
      measurements. Nevertheless, it was also demonstrated that pairs of temperature
      measurements, taken in strategic locations with respect to the interface, can
      also lead to more precise predictions of interface movement.

PMID- 20132329
TI  - A potential-based inversion of unconfined steady-state hydraulic tomography.

PMID- 20132330
TI  - Estimating reaction rate coefficients within a travel-time modeling framework.
AB  - A generalized, efficient, and practical approach based on the travel-time
      modeling framework is developed to estimate in situ reaction rate coefficients
      for groundwater remediation in heterogeneous aquifers. The required information
      for this approach can be obtained by conducting tracer tests with injection of a
      mixture of conservative and reactive tracers and measurements of both
      breakthrough curves (BTCs). The conservative BTC is used to infer the travel-time
      distribution from the injection point to the observation point. For advection
      dominant reactive transport with well-mixed reactive species and a constant
      travel-time distribution, the reactive BTC is obtained by integrating the
      solutions to advective-reactive transport over the entire travel-time
      distribution, and then is used in optimization to determine the in situ reaction
      rate coefficients. By directly working on the conservative and reactive BTCs,
      this approach avoids costly aquifer characterization and improves the estimation
      for transport in heterogeneous aquifers which may not be sufficiently described
      by traditional mechanistic transport models with constant transport parameters.
      Simplified schemes are proposed for reactive transport with zero-, first-, nth
      order, and Michaelis-Menten reactions. The proposed approach is validated by a
      reactive transport case in a two-dimensional synthetic heterogeneous aquifer and
      a field-scale bioremediation experiment conducted at Oak Ridge, Tennessee. The
      field application indicates that ethanol degradation for U(VI)-bioremediation is
      better approximated by zero-order reaction kinetics than first-order reaction
      kinetics.

PMID- 20132331
TI  - Prophylaxis in patients with haemophilia: introduction.

PMID- 20132332
TI  - Devising a best practice approach to prophylaxis in boys with severe haemophilia:
      evaluation of current treatment strategies.
AB  - Data from prospective studies clearly demonstrate the efficacy of prophylactic
      treatment of haemophilia in reducing joint- or life-threatening bleeding and the
      associated consequences for quality of life. Debate remains, however, regarding
      the optimal implementation of prophylaxis. Our aim in this review was to identify
      a best practice approach to factor replacement prophylaxis in boys with
      haemophilia. We evaluate prophylactic treatment regimens currently used in
      Swedish, Canadian and French centres and highlight key issues, including the
      optimal age for starting prophylaxis, the optimal treatment dosage/schedule and
      patient compliance.

PMID- 20132333
TI  - Assessing risk factors: prevention of inhibitors in haemophilia.
AB  - The formation of antibodies against factor VIII or factor IX that inhibit
      replacement therapy is currently the most serious treatment-related complication
      faced by patients with haemophilia. This review highlights non-modifiable and
      modifiable risk factors that determine the development of these antibodies. The
      non-modifiable risk factors include patient genotype for haemophilia,
      immunogenotype, ethnicity and positive family history. Age, intensity of
      treatment and the type of clotting factor administered are identified as
      modifiable risk factors. These risk factors are likely to be identified more
      accurately in forthcoming prospective randomized controlled trials and current
      patient registries. Through a more complete picture of a patient's overall risk
      profile, individually tailored treatment schedules might be developed that could
      minimize the incidence of inhibitor formation and thus maximize therapeutic
      benefit.

PMID- 20132334
TI  - Prophylaxis in haemophilia with inhibitors: update from international experience.
AB  - An antibody response to therapeutically administered factor VIII (FVIII) can
      occur in up to 30% of patients with haemophilia, resulting in the production of
      inhibitors that neutralize FVIII coagulant activity. Immune tolerance induction
      (ITI) therapy can be used to eradicate inhibitors in these patients, allowing
      them to continue with factor replacement therapy. Patients with inhibitors (prior
      to initiation of ITI, while on ITI or those who fail ITI) experience more
      difficulty in treating bleeds than those patients who do not develop inhibitors.
      Increasingly, prophylaxis with bypassing therapy is being employed in patients
      who develop inhibitors. Two bypassing agents, a plasma-derived activated
      prothrombin complex concentrate [aPCC (FEIBA; Baxter AG, Vienna, Austria)] and
      NovoSeven [recombinant factor VIIa (rFVIIa); NovoNordisk, Denmark] are
      potentially available for prophylaxis in patients with haemophilia who have
      developed inhibitors. Results from recent retrospective studies demonstrate the
      efficacy and safety of both aPCC and rFVIIa in decreasing the frequency of
      bleeding episodes in patients with haemophilia and inhibitors. In this article,
      we highlight a number of ongoing studies that aim to identify patients who should
      be placed on prophylaxis with bypassing agents.

PMID- 20132335
TI  - Animal models of FVIIa gene expression: their role in the future development of
      haemophilia treatment.
AB  - The development of inhibitors to replacement factor therapy is a serious
      complication in the treatment of patients with haemophilia and requires use of
      bypassing agents to prevent uncontrolled bleeding. The efficacy of recombinant
      factor VIIa (rFVIIa) as a bypassing agent in patients with haemophilia has been
      demonstrated in case studies and clinical trials. However, the perception of a
      short plasma half-life and consequent need for repeated daily injections means
      that long-term prophylaxis could potentially be limiting. Canine haemophilia
      models using a gene transfer approach have been used to evaluate the continuous
      expression of FVIIa in dogs. These studies show improvement in measurable
      bleeding parameters that have important clinical ramifications for patients with
      haemophilia. The combination of gene transfer as the method of delivery and FVII
      as the transgene overcomes issues associated with the short plasma half-life of
      rFVIIa, and represents a potentially attractive novel approach to haemostasis in
      patients with haemophilia and other platelet disorders.

PMID- 20132336
TI  - Upper cervical facet joint and spinal rami blocks for the treatment of
      cervicogenic headache.
AB  - OBJECTIVE: To evaluate the efficacy of upper cervical facet joint injections and
      spinal rami blocks in the treatment of cervicogenic headache. BACKGROUND:
      Cervicogenic headache has been recognized as a common and often disabling
      disorder. The treatment of this headache type remains challenging. METHODS: We
      conducted a retrospective chart review of 31 patients with refractory
      cervicogenic headache who underwent fluoroscopically guided C(1/2), C(2/3) facet
      joint injections and C(2), C(3) spinal rami blocks using a mixture of 0.25%
      bupivacaine and 3 mg betamehtasone. The outcome measures were the change in
      headache severity, assessed using an 11-point numerical pain scale, after
      treatment, and the duration of head pain relief. RESULTS: Twenty-eight (90.3%)
      patients experienced >50% headache relief after treatment, with an average
      duration of 21.7 (1-90) days. Mean (+/-SD) head pain intensity decreased from 7.5
      +/- 1.3 before treatment to 2.7 +/- 1.9 immediately after it (P < .0001). The
      procedures were well tolerated. CONCLUSIONS: C(1/2), C(2/3) facet joint
      injections and C(2), C(3) spinal rami blocks were effective and well tolerated
      for the treatment of cervicogenic headache in this study. The procedures provided
      significant and prolonged pain relief in the majority of patients. Larger
      controlled studies are needed to further evaluate the efficacy of this treatment
      modality in cervicogenic headache.

PMID- 20132337
TI  - Outpatient home-based continuous intravenous dihydroergotamine therapy for
      intractable migraine.
AB  - BACKGROUND: Established consecutive-day inpatient intravenous dihydroergotamine
      protocols administered by bolus intravenous injection or continuous infusion
      injection in the hospital have demonstrated efficacy and safety in modifying the
      course of daily intractable headache. We conducted a study to determine efficacy,
      tolerability, and feasibility to treat patients with daily intractable headache
      with continuous intravenous dihydroergotamine in an outpatient home-based
      setting. METHODS: A total of 31 patients fulfilling ICHD-II criteria for chronic
      daily headache, 25 with chronic migraine and 6 with medication overuse headache,
      were treated with outpatient home-based continuous intravenous dihydroergotamine
      for 3 days. Patients were pretreated with 10 mg intravenous metoclopramide prior
      to the first day of infusion and administered 3 mg dihydroergotamine given
      continuously at a rate of 42 mL/hour on day 1 and 2, and administered 1.5 mg on
      day 3 at the rate of 21 mL/hour. The primary end point was a change in pain
      intensity, as measured by an 11-point numeric pain intensity scale at the end of
      3 days. The secondary end point was reduction in headache frequency at long-term
      follow-up. RESULTS: Patients reported an average of 63.4% reduction in the
      intensity of migraine pain by the end of the 3-day infusion. Side effects were
      minimal and no serious adverse effects occurred. Approximately one-third of
      patients became completely headache-free after day 3, and 1 patient had no
      improvement. Long-term follow-up data indicated an average 86% reduction in
      headache frequency and almost every patient converted from chronic daily headache
      to episodic migraine except for 1 patient. Patients with medication overuse
      headache were no longer consuming the daily offending medication. CONCLUSIONS:
      Efficacy and safety of our outpatient home-based intravenous dihydroergotamine
      program compared favorably to that of established inpatient intravenous pulse
      injection and continuous infusion protocols for the treatment of intractable
      migraine. The use of outpatient continuous intravenous dihydroergotamine is an
      effective and well-tolerated therapy for intractable migraine but without the
      added cost and inconvenience of hospitalization.

PMID- 20132338
TI  - Microembolic air load during contrast-transcranial Doppler: a trigger for
      migraine with aura?
AB  - BACKGROUND: There is a well-known association between migraine with aura (MA) and
      right-to-left shunt (RILES) because of patent foramen ovale (PFO). The occurrence
      of MA attacks after microbubble (MB) injection during contrast-enhanced
      transcranial Doppler (ce-TCD) has been recently described. OBJECTIVES: The aim of
      this study was to analyze the prevalence of RILES in a consecutive cohort of MA
      patients and to characterize the occurrence of MA attacks after diagnostic ce
      TCD. METHODS: A total of 159 consecutive MA patients underwent ce-TCD with air
      mixed saline to disclose RILES. RILES was characterized in terms of MB amount
      (small-moderate or large) and occurrence at rest and/or during Valsalva maneuver
      (permanent or latent). RESULTS: RILES was revealed in 79/159 patients (~ 50%).
      Permanent RILES were detected in 56/79 (71%) and latent RILES in 23/79 (29%) MA
      patients. The occurrence of a typical MA attack was overall observed in 12/159
      patients (7.5%; 95% CI: 4-12.8%), but arose only in RILES-positive ones,
      immediately after ce-TCD (12/79; 15.2%; P< .001). All 12 patients had permanent
      RILES (12/56; 21.4%; P= .015) and MA attack was mostly observed in large RILES
      positive patients, even without statistical significance (P= .118). CONCLUSIONS:
      Microembolic air load could act as a trigger of MA attack. According to recent
      studies and to the clinical characteristics observed in our patients,
      microembolization because of MB injection might provoke a decrease in cerebral
      oxygen saturation, thus triggering cortical spreading depression and, thereafter,
      MA attack. Larger and prospective studies will be necessary to confirm our data
      and observe a wider correlation.

PMID- 20132339
TI  - Triptan exposure during pregnancy and the risk of major congenital malformations
      and adverse pregnancy outcomes: results from the Norwegian Mother and Child
      Cohort Study.
AB  - OBJECTIVE: To evaluate the safety of triptan therapy during pregnancy.
      BACKGROUND: Information on the safety of triptan therapy during pregnancy is
      scarce and only available for sumatriptan, naratriptan, and rizatriptan. No
      associations with congenital malformations have been detected so far, but one
      study found a significant association between sumatriptan exposure during
      pregnancy and prematurity. METHODS: The study population consisted of 69,929
      pregnant women and their newborn children for whom data on drug exposure and
      pregnancy outcome were available. Information on triptan therapy and potential
      socio-demographic and medical confounding factors was obtained from the Norwegian
      Mother and Child Cohort Study. Information on congenital malformations and other
      adverse pregnancy outcomes was obtained from the Norwegian Medical Birth
      Registry. The datasets were linked via the women's personal identification
      number. Pearson's chi(2) tests and logistic regression analyses were used to
      identify associations between triptan therapy and pregnancy outcome. RESULTS: No
      significant associations between triptan therapy during the first trimester and
      major congenital malformations (unadjusted OR: 1.0; 95% CI 0.8-1.3, adjusted OR:
      1.0; 95% CI 0.7-1.2) or other adverse pregnancy outcomes were found. Triptan
      therapy during the second and/or third trimesters was significantly associated
      with atonic uterus (unadjusted OR: 1.5; 95% CI 1.1-1.9, adjusted OR: 1.4; 95% CI
      1.1-1.8), and blood loss >500 mL during labor (unadjusted OR: 1.3; 95% CI 1.1
      1.5, adjusted OR: 1.3; 95% CI 1.1-1.5). CONCLUSIONS: Triptan therapy during
      pregnancy was not associated with an overall increased risk of congenital
      malformations. It cannot, however, be excluded that a difference in the risk
      between triptan use and individual or rare congenital malformations may exist. A
      slight increase in the risk of atonic uterus and hemorrhage was associated with
      triptan use during the second and/or third trimesters. Although the present
      findings are reassuring, confirmation in independent studies is warranted.

PMID- 20132340
TI  - Distinct pharmacokinetic profile and safety of a fixed-dose tablet of sumatriptan
      and naproxen sodium for the acute treatment of migraine.
AB  - OBJECTIVE: To describe the pharmacokinetic and safety profiles of sumatriptan 85
      mg formulated with RT Technology (RT) and naproxen sodium 500 mg in a fixed-dose
      combination tablet (sumatriptan/naproxen sodium) that targets both serotonergic
      dysmodulation and inflammation in migraine. METHODS: Six open-label, crossover
      studies were conducted in healthy volunteers (Studies 1, 2, 3, 4, 5) or patients
      with migraine (Study 6). RESULTS: Consistently across studies, naproxen
      administered as a component of sumatriptan/naproxen sodium demonstrated a delayed
      release profile similar to that of an enteric-coated product. Naproxen from the
      combination tablet showed a delayed time to peak plasma concentration and lower
      peak plasma concentration while exposures (area under the plasma concentration
      time curve) were similar. The peak plasma concentration for naproxen was
      approximately 36% lower and the time to peak plasma concentration approximately 4
      hours later when naproxen was administered as sumatriptan/naproxen sodium
      compared with a single naproxen sodium 550 mg tablet. Sumatriptan peak plasma
      concentration and area under the plasma concentration-time curve after
      administration of sumatriptan/naproxen sodium (containing sumatriptan 85 mg) were
      comparable to those after administration of a commercially available sumatriptan
      100 mg (RT) tablet. Sumatriptan time to peak plasma concentration occurred, on
      average, 30 minutes earlier with sumatriptan/naproxen sodium compared with
      sumatriptan 100 mg (RT). No clinically significant differences between
      sumatriptan/naproxen sodium and sumatriptan tablets 100 mg (RT) were identified
      with respect to electrocardiograms, blood pressure, or heart rate. In addition,
      food had no significant effect on the bioavailability of naproxen or sumatriptan
      after administration of sumatriptan/naproxen sodium but slightly delayed the time
      to peak plasma concentration of sumatriptan by approximately 40 minutes. The
      pharmacokinetics of sumatriptan and naproxen did not differ according to whether
      sumatriptan/naproxen sodium was administered during a migraine attack or a
      migraine-free period. The pharmacokinetics of 2 sumatriptan/naproxen sodium
      tablets administered 2 hours apart were consistent with the pharmacokinetic
      predictions from a single dose of the combination tablet. The adverse-event
      profile of the sumatriptan/naproxen sodium combination tablet did not appear to
      differ from that of the individual components of the same or similar dosage
      strengths administered alone or in combination. In addition, the incidence of
      adverse events with 2 sumatriptan/naproxen sodium tablets administered 2 hours
      apart was lower than that with the single dose. CONCLUSION: The combination
      tablet of sumatriptan/naproxen sodium has unique pharmacokinetic properties. The
      rapid absorption of sumatriptan with the delayed-release properties of naproxen
      sodium from sumatriptan/naproxen sodium might contribute to its therapeutic
      advantage over monotherapy with either component. No clinically meaningful
      effects of food, administration during a migraine attack, or administration of a
      second tablet (2 hours after initial dose) on the pharmacokinetics or safety of
      sumatriptan/naproxen sodium were observed.

PMID- 20132341
TI  - Using information on clinical conditions to predict high-cost patients.
AB  - OBJECTIVE: To compare the ability of different models to predict prospectively
      whether someone will incur high medical expenditures. DATA SOURCE: Using
      nationally representative data from the Medical Expenditure Panel Survey (MEPS),
      prediction models were developed using cohorts initiated in 1996-1999 (N=52,918),
      and validated using cohorts initiated in 2000-2003 (N=61,155). STUDY DESIGN: We
      estimated logistic regression models to predict being in the upper expenditure
      decile in Year 2 of a cohort, based on data from Year 1. We compared a summary
      risk score based on diagnostic cost group (DCG) prospective risk scores to a
      count of chronic conditions and indicators for 10 specific high-prevalence
      chronic conditions. We examined whether self-rated health and functional
      limitations enhanced prediction, controlling for clinical conditions. Models were
      evaluated using the Bayesian information criterion and the c-statistic. PRINCIPAL
      FINDINGS: Medical condition information substantially improved prediction of high
      expenditures beyond gender and age, with the DCG risk score providing the
      greatest improvement in prediction. The count of chronic conditions, self
      reported health status, and functional limitations were significantly associated
      with future high expenditures, controlling for DCG score. A model including these
      variables had good discrimination (c=0.836). CONCLUSIONS: The number of chronic
      conditions merits consideration in future efforts to develop expenditure
      prediction models. While significant, self-rated health and indicators of
      functioning improved prediction only slightly.

PMID- 20132342
TI  - Patient navigation: development of a protocol for describing what navigators do.
AB  - OBJECTIVE: To develop a structured protocol for observing patient navigators at
      work, describing and characterizing specific activities related to their goals.
      DATA SOURCES/SETTING: Fourteen extended observations of navigators at three
      programs within a national trial of patient navigation. STUDY DESIGN: Preliminary
      observations were guided by a conceptual model derived from the literature and
      expert consensus, then coded to develop and refine observation categories. These
      findings were then used to develop the protocol. METHODS: Observation fieldnotes
      were coded, using both a priori codes and new codes based on emergent themes.
      Using these codes, the team refined the model and constructed an observation tool
      that enables consistent categorization of the observed range of navigator
      actions. FINDINGS: Navigator actions across a wide variety of settings can be
      categorized in a matrix with two dimensions. One dimension categorizes the
      individuals and organizational entities with whom the navigator interacts; the
      other characterizes the types of tasks carried out by the navigators in support
      of their patients. CONCLUSIONS: Use of this protocol will enable researchers to
      systematically characterize and compare navigator activities within and across
      programs.

PMID- 20132343
TI  - Health care reform: what the United States can learn from the experience of other
      developed nations.

PMID- 20132344
TI  - Macrophage activity in semen is significantly correlated with sperm quality in
      infertile men.
AB  - The presence of leucocytes within semen has the potential to impair sperm
      function. Neutrophils and macrophages make up 95% of seminal leucocytes, with
      both having the ability to damage sperm via the generation of reactive oxygen
      species, proteases and the induction of apoptosis. Existing cytological
      techniques for quantifying leucocyte activity within semen (peroxidase, CD45) are
      less than ideal as they merely count the number of leucocytes, rather than assess
      their activity. Seminal plasma elastase effectively determines neutrophil
      activity, yet gives no insight into macrophage activity. Neopterin, a molecule
      released from activated macrophages, may be a useful marker for macrophage
      activity in the male reproductive tract. To examine this possibility a total of
      63 asymptomatic subjects with male factor infertility and 11 fertile controls
      provided semen samples for measurement of various inflammatory markers. We were
      able to confirm for the first time that seminal plasma does indeed contain
      neopterin and that the levels of this macrophage activity marker are threefold
      higher in infertile than fertile men. Furthermore, seminal plasma neopterin
      concentration was significantly correlated with sperm oxidative stress, DNA
      fragmentation (TUNEL) and apoptosis (Annexin V), making it a useful marker of
      sperm quality. By contrast, seminal plasma elastase showed no correlation with
      any marker of sperm quality.

PMID- 20132345
TI  - Mixture effects of endocrine disrupting compounds in vitro.
AB  - Four different equi-molar mixtures were investigated for additive endocrine
      disrupting effects in vitro using the concentration addition model. It was found
      that additive effects on the same molecular target (the androgen receptor; AR)
      can be predicted for both mixtures of compounds with effect on the AR (flutamide,
      procymidone and vinclozolin) and of compounds with and without effects on the AR
      [finasteride, mono-(2-ethylhexyl) phthalate, prochloraz and vinclozolin]. For a
      paraben mixture (methyl paraben, ethyl paraben, propyl paraben, butyl paraben and
      iso-butyl paraben) antagonistic effect on AR could not be predicted under
      assumption of additivity in our model system. For a mixture containing three
      azole fungicides (epoxiconazole, propiconazole and tebuconazole), the observed AR
      antagonistic effects were close to the predicted effect assuming additivity.
      Azole fungicides are known inhibitors of androgen biosynthesis and in the steroid
      synthesis assay using H295R cells, the inhibition of testosterone production was
      close to additive, whereas the inhibition of oestradiol production was over
      estimated for the mixture of azole fungicides, when compared with the effect
      predicted when assuming additivity. Overall these and other studies show that
      weak endocrine disrupting compounds, like parabens and azole fungicides, give
      rise to combination effects when they occur in mixtures. These combination
      effects should be taken into account in regulatory risk assessment not to under
      estimate the risks for adverse effects associated with exposure to disrupting
      chemicals.

PMID- 20132346
TI  - Undervirilization in XY newborns may hide a 5alpha-reductase deficiency: report
      of three new SRD5A2 gene mutations.
AB  - The observation of ambiguous genitalia in the newborn signals a medical, surgical
      and psychological emergency. The most crucial decision will be the choice of sex
      assignment. Rapid and precise diagnosis is thus essential. In XY newborns with
      normal/high plasma testosterone (T), partial androgen insensitivity syndrome
      (PAIS) is usually the first diagnosis evoked, which implies an androgen receptor
      (AR) defect. The diagnosis of steroid-5-alpha-reductase deficiency is rarely
      considered by the paediatrician. We report three new SRD5A2 gene mutations in
      four newborns from France, Morocco and Turkey. The newborns presented with
      ambiguous genitalia and normal plasma T values and the initial diagnosis?PAIS. In
      all four cases, normal sequences of the complete AR gene excluded this diagnosis
      and raised the hypothesis of 5alpha-reductase deficiency. The entire coding
      region (5 exons) of the SRD5A2 gene was assessed by PCR and direct sequencing
      analysis. For patient 1, we identified a new homozygous 2bp deletion in exon 1
      (c.122_123delAG). Patient 2 had a known homozygous mutation, p.G115D, in exon 2.
      New compound heterozygous mutations in exon 4 (p.A215V) and exon 5 (p.X255Q) were
      found in patient 3. Patient 4 presented a new substitution in exon 1 (p.S14R)
      associated with a known polymorphism (p.V89L). Our data confirm our previous
      experience and clearly demonstrate that a 5-alpha reductase defect should be
      considered in all XY newborns with ambiguous genitalia and normal plasma T
      secretion, whatever their geographic area or ethnic group; moreover, this defect
      was not linked to specific phenotype. Early molecular diagnosis is indispensable
      for the crucial decision of the newborn's sex of rearing.

PMID- 20132347
TI  - Effect of microsurgical varicocelectomy on human sperm chromatin and DNA
      integrity: a prospective trial.
AB  - There is evidence from retrospective studies that varicocelectomy can improve
      sperm DNA damage in infertile men with a clinical varicocele. The objective of
      this prospective study was to examine further the effect of varicocelectomy on
      sperm chromatin and DNA integrity. We evaluated a consecutive series of infertile
      men (n = 25) who underwent microsurgical varicocelectomy for treatment of
      clinical varicocele. We examined conventional sperm parameters and sperm
      chromatin structure assay parameters (percentage DFI--DNA fragmentation index and
      percentage HDS--high DNA stainability, an index of chromatin compaction) before
      and 4 and 6 months after microsurgical varicocelectomy. Sperm DNA integrity
      improved significantly after surgery (percentage DFI decreased from 18 +/- 11%
      before surgery to 10 +/- 5%, and 7 +/- 3%, at 4 and 6 months after surgery
      respectively). Sperm chromatin compaction also improved significantly after
      surgery (percentage HDS decreased from 11 +/- 7% before surgery to 8 +/- 6%, and
      7 +/- 5%, at 4 and 6 months after surgery, respectively). Sperm concentration and
      progressive motility improved after surgery, although the differences were not
      statistically significant when compared with that before surgery. The data show
      that varicocelectomy is associated with an improvement in sperm DNA integrity and
      chromatin compaction. These findings support the concept that correction of a
      varicocele can improve spermatogenesis, particularly spermiogenesis (the stage in
      spermatogenesis where compaction and stability of the sperm DNA and chromatin
      occur).

PMID- 20132348
TI  - Testicular dysgenesis syndrome comprises some but not all cases of hypospadias
      and impaired spermatogenesis.
AB  - In 2001, when the testicular dysgenesis syndrome (TDS) concept was proposed, it
      suggested that impaired development of foetal testes could lead to increased
      risks of cryptorchidism, hypospadias, decreased spermatogenesis or testis cancer.
      The TDS concept links the pathogenesis of the four disorders together, but does
      not imply that all affected men develop all four symptoms. The least affected men
      may merely have a slightly reduced spermatogenic capacity, and only the most
      severely affected may present all symptoms. A majority of cases of testicular
      germ cell cancers (TGCC) and cryptorchidism are most likely caused by TDS.
      However, the frequency of the syndrome in the general population and to what
      extent poor semen quality and hypospadias are actually biologically related
      through a foetal mechanism remain unresolved. Hypospadias and impaired
      spermatogenesis can be classified as TDS if combined with cryptorchidism or TGCC.
      By contrast, recent studies demonstrated that among men with isolated
      hypospadias, only a fraction of cases are linked to TDS. There is no doubt that
      TDS contributes to impaired semen quality. This is most obvious for cases with
      visible dysgenetic features in testis histology, but in the majority of men with
      impaired semen quality as the only symptom, an association with TDS is less
      clear. Such cases have a very heterogeneous aetiology and may be caused by a host
      of other - often post-natal-factors. In conclusion, the TDS as a holistic concept
      has inspired new research activities and led to a better understanding of the
      early origin of male reproductive problems, but it clearly encompasses only a
      fraction of cases of hypospadias and impaired spermatogenesis.

PMID- 20132349
TI  - Measurement and correlates of ano-genital distance in healthy, newborn infants.
AB  - Ano-genital distance (AGD) is a sexually dimorphic trait that is a well
      established reproductive toxicity endpoint in animals. In male animals, a
      shortened AGD is associated with a variety of genital abnormalities including
      hypospadias and cryptorchidism. Consensus on the anatomical definition of AGD in
      humans remains to be established and few data exist on the determinants and
      normal variance in the general population. We implemented a standardized
      anthropometric protocol to measure AGD, ano-scrotal distance (ASD), and ano
      fourchette distance (AFD) in 169 (82 male, 87 female) infants in the University
      of Washington newborn nursery in 2008. We collected data on the following
      characteristics: weight, length, and occipital head circumference, race and
      relevant gestational complications. Using linear regression modelling, we
      examined AGD/ASD/AFD for sexual dimorphism, normal population variance and
      predictors of the measurement in infants. The mean male and female AGD
      measurements were 52.0 mm (SD +/- 5.5) and 37.2 mm (SD +/- 3.7). The mean ASD and
      AFD were 23.0 mm (SD +/- 3.8) and 15.1 mm (SD +/- 2.9). Weight, length, occipital
      head circumference and gestational age were associated with AGD (p < 0.05).
      Weight and length were the most important correlates to AGD. We confirmed
      previous findings that AGD is a sexually dimorphic measurement that is most
      strongly predicted by infant weight. The application of this measurement to
      clinically relevant outcomes remains to be explored in further depth.

PMID- 20132350
TI  - Evaluation of the CellaVision DM automated microscope in pediatrics.
AB  - The DM is an automated microscope, which performs WBC differential counts and
      monitors red cell morphology. The user either validates the cell recognition if
      the DM has correctly identified the WBCs or reclassifies the WBCs in the good
      category in case of a DM mis-assignment. Morphological anomalies of leukocytes,
      red blood cells or platelets are analyzed and registered. We studied 521 newborns
      and infants sorted by age and pathology. The results correlated well with those
      using conventional microscopy except for samples containing blasts, in which the
      percentage of malignant cells was underestimated. Newborns had the lowest rates
      of overall accuracy and postclassification agreement. For red cell analysis, 10%
      of the selected areas were considered unreadable. However, the DM diagnosed
      faithfully all studied red cell pathologies. The DM was also very useful in
      analyzing samples of storage diseases. Timesavings ranging from 1 up to 10 min
      (for vacuolated lymphocyte screening) were observed when performing analysis with
      the DM. The DM represents a useful diagnostic and training tool. However,
      conventional microscopy remains essential, in particular when the image quality
      is poor, such as in the case of lymphoblasts, and in the screening of platelet
      clusters.

PMID- 20132353
TI  - An educational strategy for teaching standardized nursing languages.
AB  - PURPOSE. The aim of this paper is to describe an educational strategy for
      teaching standardized nursing languages (SNL) used in both the classroom and
      clinical components of a psychiatric-mental health nursing course at the
      associate degree level. DATA SOURCES. Data included a review of the relevant
      literature, teaching experiences, and faculty and student experiences. DATA
      SYNTHESIS. Enhancing associate degree student nurses' competency regarding
      diagnosis and interventions is essential to influence positive health outcomes.
      Use of diagnostic, outcome, and intervention classifications for learning nursing
      care promotes critical thinking, individualization of nursing care, and students'
      fluency with SNL. One possible teaching strategy to assist students to learn and
      use SNL was implemented through the use of a faculty-developed Student Nurse
      Documentation Packet. CONCLUSIONS. The educational strategy provided students
      opportunities to enhance their experience with the SNL to plan and document care
      of individuals experiencing psychiatric-mental health problems. IMPLICATIONS FOR
      NURSING. The educational strategy used in this program was judged to be
      successful. Research is needed to provide empirical evidence of the efficacy of
      this pedagogical strategy for increasing knowledge and enhancing students'
      competency.

PMID- 20132354
TI  - Aging as a related factor of the nursing diagnosis impaired memory: content
      validation.
AB  - PURPOSE. The purpose of this study was to conduct a content validation for the
      elements of the nursing diagnosis Impaired Memory and include aging as a related
      factor. METHOD. Fehring's (1987) model of diagnosis content validation was used,
      with the participation of 18 experts. FINDING. The definition, defining
      characteristics, and related factors of NANDA-I were evaluated by experts, as was
      the proposed related factor "aging." CONCLUSIONS. Elements of the NANDA-I
      diagnosis Impaired Memory and the proposed related factor of aging were validated
      in the Brazilian context. A clinical validation of this related factor will be
      necessary to build evidence for this relationship. IMPLICATIONS FOR NURSING
      PRACTICE. NANDA-I diagnoses should be tested and validated in the elderly, in
      order to take their specific needs into account, thus contributing to quality
      nursing care for these patients.

PMID- 20132355
TI  - A comparison of the concept of patient participation and patients' descriptions
      as related to healthcare definitions.
AB  - PURPOSE. To depict what patients describe as patient participation and whether
      descriptions of patient participation are affected by gender, age, healthcare
      contact, and duration of disease. DATA SOURCES. Current patients (n= 362)
      responded to a questionnaire on participation. DATA SYNTHESIS. Patients'
      descriptions focused on having knowledge, rather than being informed, and on
      interacting with health professionals, rather than merely partaking in decision
      making. CONCLUSIONS. Patients' descriptions of participation correspond with the
      International Classification of Functioning, Disability and Health's definition,
      which includes "being involved in a life situation." Healthcare legislation and
      professionals employ a narrower concept of patient participation as defined by,
      e.g., Medical Subject Headings. PRACTICE IMPLICATIONS. Findings suggest that
      health professionals need to embrace what patients describe as participation.

PMID- 20132356
TI  - An interview with Marilynn Doenges, Mary Moorhouse, and Alice Murr. Interviewed
      by Maria Muller-Staub and Matthias Odenbreit.

PMID- 20132357
TI  - Nurse anesthetist follow-up of an adolescent female with gunshot trauma: a case
      study.
AB  - PURPOSE. This case study was written to demonstrate the usefulness of
      standardized nursing diagnoses, outcomes, and interventions in nurse anesthetist
      care of an adolescent trauma patient. DATA SOURCES. Literature reviews using
      Academic Premier, Google Scholar, and CINAHL databases were done to find current,
      relevant articles concerning evaluation and support of female African-American
      adolescents living in socially vulnerable and economically exploited
      environments. DATA SYNTHESIS. A case is presented and evidence from current
      publications is analyzed to support the diagnosis, outcomes, and interventions.
      CONCLUSION. The investment in extra time, care, and effort sometimes required for
      the full development of a treatment plan for teenagers who live where they are at
      high risk for violence and other consequences of stressful environments is a
      worthwhile one, even if results may require contact over an extended time period.
      PRACTICE IMPLICATIONS. Nurses of all specialty backgrounds need to be concerned
      with the progress of their patients. Sometimes nurses can best serve their
      patients by stepping away from the physiological event and focusing instead on
      responses in the domain of coping and stress tolerance as the root of
      difficulties.

PMID- 20132360
TI  - Editorial Comment to Development and internal validation of a nomogram predicting
      extracapsular extension in radical prostatectomy specimens.

PMID- 20132361
TI  - Development and internal validation of a nomogram predicting extracapsular
      extension in radical prostatectomy specimens.
AB  - OBJECTIVES: To present a nomogram predicting the side-specific probability of
      extracapsular extension (ECE) in radical prostatectomy (RP) specimens. METHODS:
      Three hundred and fifty-four patients with T1c-T3a prostate cancer undergoing RP
      were included in the analysis. A receiver operating characteristic (ROC) analysis
      was carried out to evaluate the predictive values of each clinical and
      pathological factor, separately and in combination. Based on logistic regression
      analysis, a nomogram predicting the side-specific probability of ECE was
      developed. RESULTS: Overall, 146 (40%) of 354 patients and 165 (23%) of 708 lobes
      had ECE pathologically. The areas under the ROC curve (AUC) of the standard
      features, such as serum PSA, clinical stage and biopsy Gleason sum on each side,
      in predicting side-specific probability of ECE were 0.624, 0.627, and 0.747,
      respectively. When these three features were combined, AUC increased to 0.773
      which was not significantly different from 0.791 of maximum percent of cancer
      alone (P = 0.613) and significantly enhanced by including maximum percent of
      cancer on each side, 0.799 (P = 0.022). The resulting nomogram was internally
      validated and had excellent calibration. CONCLUSIONS: The accuracy in predicting
      ECE is increased by combining standard clinical factors (clinical stage, serum
      PSA, highest Gleason score) and biopsy features, such as maximum percent of
      cancer in the cores. The developed nomogram is helpful when deciding whether or
      not neurovascular bundles can be preserved.

PMID- 20132362
TI  - The future of urodynamics: non-invasive ultrasound videourodynamics.
AB  - A totally non-invasive transperineal urodynamic technique using Doppler
      ultrasonography has been developed. Normal urine doesn't have blood cells so
      urine was thought not to produce Doppler effects. However, basic studies
      confirmed that the decrease of pressure at high velocity (Bernoulli effects)
      caused dissolved gas to form microbubbles, which are detected by Doppler
      ultrasonography. Subjects sat and a probe was advanced via remote control to
      achieve gentle contact with the perineal skin. The digital uroflow data signals
      and the color Doppler ultrasound video images were processed on a personal
      computer. This method was viable to diagnose the degree of bladder outlet
      obstruction. The advantage of being rapid, effective, and equipped with no
      special attachments allows it to surpass any other non-invasive urodynamic
      methods. The difference between the echocardiogram and the ultrasound urodynamic
      system is only the frequency of obtaining velocity information: more than 50
      times per minute vs once every several hours, respectively. Although the
      ultrasound urodynamic system is more difficult to develop than the
      echocardiogram, one principle is shared by both methods. The patient can void
      freely without interruptions, there is no contact between the penis and the
      equipment and it is specifically directed toward non-invasive diagnosis. The
      development of non-invasive Doppler ultrasound videourodynamics will dramatically
      expand understanding of voiding function.

PMID- 20132363
TI  - Health promotion/risk reduction and disease prevention in women's health.

PMID- 20132364
TI  - Coronary heart disease knowledge tool for women.
AB  - PURPOSE: To develop a tool that measures coronary heart disease (CHD) knowledge
      specifically for women. DATA SOURCES: The new CHD knowledge tool, based on
      previous surveys of women's CHD knowledge, has 25 multiple-choice questions. An
      expert panel evaluated content and face validity. The tool was pilot tested in
      women without CHD, who were admitted to a Chest Pain Center. The tool was
      subsequently administered to laywomen and female cardiovascular nurses to
      evaluate its validity and reliability. The sample included 49 women as the
      control group (Group 1), 23 cardiovascular nurses as a known group (Group 2), and
      22 women with an educational program as the treatment group (Group 3). Knowledge
      of women in Group 1 was compared with Groups 2 and 3 in known group and
      predictive validity tests. CONCLUSION: The new tool demonstrates good validity
      and reliability to measure CHD knowledge in women. IMPLICATIONS FOR PRACTICE:
      Women continue to have low CHD knowledge, and nurse practitioners should provide
      education to improve women's CHD knowledge as a strategy to promote healthy
      lifestyle practices and CHD risk prevention. The new tool can be utilized in
      future research to measure women's CHD knowledge.

PMID- 20132365
TI  - A triad of evidence for care of women with genital piercings.
AB  - PURPOSE: To add three further dimensions of evidence for the care of women with
      genital piercings (GPs). DATA SOURCES: Following a literature review, a cross
      sectional study replicated previous work, using a web-based survey. This triad of
      evidence provides (a) descriptive quantitative data (N = 240) about women with
      GPs, (b) qualitative data about women with GPs, as well as (c) clinical
      observations from 60 healthcare providers (HCPs) who have cared for women with
      GPs. CONCLUSIONS: Three important findings about women with GPs were validated:
      (a) GPs were deliberate actions, sought for personal and sexual expression; (b)
      women with GPs treat piercings as a normal, meaningful part of their lives which
      produce sexual enhancement and expression; and (c) they continue to seek
      information about GP care from nonhealth providers. New data indicate that they
      have experienced depression (47%), abuse (physical 18%; emotional, 27%; sexual,
      14%), and forced sexual activity (35%) in their lives. Several unsubstantiated
      assumptions about women with GPs are challenged with these data. IMPLICATIONS FOR
      PRACTICE: GPs should not delay important health care. Health-protective, as well
      as health promotion, behaviors are important to reduce risks. Nurse practitioners
      (NPs) can become effective and resourceful advocates in three specific areas of
      care: (a) responsiveness to women with GPs, (b) collaborative decision making for
      the removal of jewelry, and (c) promotion of applicable patient education.

PMID- 20132366
TI  - Considerations for the use of progestin-only contraceptives.
AB  - PURPOSE: To highlight the characteristics of progestin-only contraceptives (POCs)
      currently available in the United States, and to explore the potential of these
      agents as first-line contraceptive options for women seeking health promotion by
      prevention of an unwanted pregnancy. The progestin-only pills (Micronor and
      Ovrette), depot medroxyprogesterone acetate (DMPA) injections (Depo-Provera and
      depo-subQ provera 104), levonorgestrel intrauterine system (IUS) (Mirena), and
      etonogestrel implant (Implanon) will be reviewed. The use of levonorgestrel (Plan
      B) as an emergency contraceptive will also be considered briefly. DATA SOURCES:
      Worldwide medical literature and the prescribing information for the specified
      products. CONCLUSIONS: A number of POCs are currently available for routine birth
      control in the United States, ranging from the daily progestin-only pill to
      nondaily contraceptive options such as injectable DMPA, the levonorgestrel
      releasing IUS, and the etonogestrel-releasing contraceptive implant. Each of
      these methods has specific advantages, but also specific drawbacks that can
      result in discontinuation of treatment if users are not given adequate
      information about what to expect in terms of side effects. It is critical that
      clinicians provide adequate and accurate information along with detailed
      counseling to women who are considering using POCs, as well as providing periodic
      reinforcement of the information at regular clinic visits for those already using
      POCs. IMPLICATIONS FOR PRACTICE: Given that a large number of pregnancies are
      unplanned and create a significant impact on social, economic, and health
      outcomes, it is important for the clinician to have a vast knowledge of
      contraceptive options. POCs offer significant choices in contraception. By
      proactively addressing common concerns (such as potential effects on weight,
      mood, menstrual bleeding patterns, and bone mineral density), clinicians may
      improve the likelihood of adherence and continuation with POCs for routine birth
      control.

PMID- 20132367
TI  - The human papillomavirus in women over 40: implications for practice and
      recommendations for screening.
AB  - PURPOSE: Cervical cancer is the second leading cause of cancer deaths among women
      worldwide. Human papillomavirus (HPV) has been shown to be the precursor of
      cervical cancer in over 99% of these cases. Although preventative measures have
      greatly reduced the burden of HPV-induced cervical cancer, these measures cannot
      be utilized by women who are unaware of the existence of HPV and its relationship
      to their health. Women over the age of 40 are being newly diagnosed with HPV,
      profoundly impacting their lives and their sense of well-being. This article
      highlights the necessity for clinicians to assess knowledge, health beliefs, and
      preventative measures regarding HPV and cervical cancer in women over the age of
      40. DATA SOURCES: Review of scientific literature of knowledge, health beliefs,
      and preventative measures in women regarding HPV and cervical cancer and clinical
      practice guidelines. CONCLUSIONS: Although women aged 40 and above are not
      specifically considered high risk for HPV infection, many women are testing
      positive in this age group and are facing the impact of an HPV diagnosis that
      implicates a sexually transmitted disease and is known to be a precursor to
      cervical cancer. IMPLICATIONS FOR PRACTICE: Suggested questions to use for all
      patients are presented as it is crucial for healthcare providers to understand
      the healthcare needs of this age group in order to appropriately direct resources
      and to save the lives of women from this preventable disease.

PMID- 20132368
TI  - Evidence of African-American women's frustrations with chronic recurrent
      bacterial vaginosis.
AB  - PURPOSE: The purpose of this study was to explore the impact of recurrent
      bacterial vaginosis (BV) and its treatment on quality of life (QOL), acceptance
      of current treatment options, and psychosocial issues related to lifestyle
      practices associated with BV. DATA SOURCES: Qualitative and quantitative data
      were obtained from 23 African American women with recurrent BV. Participants
      completed a short survey, developed by the researchers based on a prior study
      which examined factors associated with recurrent BV, and a one-on-one interview
      assessing the impact of BV, current treatment modalities, and lifestyle practices
      related to recurrent BV. CONCLUSIONS: Emerging themes suggest that recurrent BV
      is associated with psychosocial issues that are currently not addressed in a
      typical office visit. Reported feelings of shame and embarrassment often cause
      women to engage in hypervigilant routines of hygiene that negatively impact their
      professional, personal, and intimate relationships, significantly affecting their
      QOL. IMPLICATIONS FOR PRACTICE: Without proper education, advice, and support, BV
      is perpetuated by lifestyle practices leading to recurrent infection and
      associated symptoms. With proper guidance, it is expected that women with
      recurrent BV will see an improvement in their QOL, with fewer complications from
      BV infection, and healthy relationships with intimate partners, family, and
      friends.

PMID- 20132369
TI  - Diagnosis and management of endometriosis: the role of the advanced practice
      nurse in primary care.
AB  - PURPOSE: To discuss the etiology, clinical presentation, diagnosis, and
      management of endometriosis for the advanced practice nurse (APN) in primary
      care. DATA SOURCES: Selected research, clinical studies, clinical practice
      guidelines, and review articles. CONCLUSIONS: Commonly encountered by the APN in
      primary care, endometriosis is a chronic, progressive inflammatory disease
      characterized by endometrial lesions, cysts, fibrosis, or adhesions in the pelvic
      cavity, causing chronic pelvic pain and infertility in women of reproductive age.
      Because of its frequently normal physical examination findings, variable clinical
      presentations, and nonspecific, overlapping symptoms with other conditions,
      endometriosis can be difficult to diagnose. As there currently are no accurate
      noninvasive diagnostic tests specific for endometriosis, it is imperative for the
      APN to become knowledgeable about the etiology, clinical presentation, diagnosis,
      and current treatment options of this disease. IMPLICATIONS FOR PRACTICE: The APN
      in primary care plays an essential role in health promotion through disease
      management and infertility prevention by providing support and much needed
      information to the patient with endometriosis. APNs can also facilitate quality
      of care and manage treatments effectively to improve quality of life, reduce
      pain, and prevent further progression of disease. Practice recommendations
      include timely diagnosis, pain management, infertility counseling, patient
      education, and support for quality of life issues.

PMID- 20132370
TI  - If pelvic inflammatory disease is suspected empiric treatment should be
      initiated.
AB  - PURPOSE: To assist the nurse practitioner (NP) to make a rapid diagnosis and
      develop a treatment plan for pelvic inflammatory disease (PID) in order to assist
      women to promote their health and reduce their risk of the unnecessary sequelae
      of infertility, tubal damage, and the possibility of a subsequent ectopic
      pregnancy. DATA SOURCES: Centers for Disease Control guidelines and recent
      clinical practice literature were searched to provide guidance on how to
      diagnose, treat, and educate the patient with PID. CONCLUSIONS: The incidence of
      PID is approximately 1 million women annually. PID is diagnosed in 1%-2% of
      sexually active women under the age of 25, with a higher incidence in African
      American women. Women with PID produce over 2 million emergency room and office
      visits and incur health care costs of over 4 billion dollars annually.
      IMPLICATIONS FOR PRACTICE: PID is associated with chronic pelvic pain,
      infertility, and ectopic pregnancy. Symptoms can range from subtle and indolent
      to acute and fulminant. Having a high index of suspicion for the diagnosis will
      assist the NP in treating patients with this disease. Empiric antibiotic therapy
      should be initiated in all women at risk who have uterine, adnexal, or cervical
      motion tenderness on a bimanual exam with no other explanation for these
      symptoms. Without response to treatment, if the diagnosis is unclear, or if a
      surgical emergency is being considered, prompt referral to a specialist is
      warranted. Secondary preventive measures are discussed.

PMID- 20132371
TI  - Consequences of 'load-lightening' for future indirect fitness gains by helpers in
      a cooperatively breeding bird.
AB  - 1. Helpers that invest energy in provisioning the offspring of related
      individuals stand to gain indirect fitness benefits from doing so. First, if the
      helper's effort is additional to that of the parents (additive) the productivity
      of the current breeding attempt can be increased. Secondly, if the parents reduce
      their workload (compensation) this can result in future indirect fitness gains to
      the helper via increased breeder survival; termed 'load-lightening'. 2. Long
      tailed tits (Aegithalos caudatus) have a cooperative breeding system in which
      helpers assist kin and parents exhibit both additive and compensatory reactions
      in the presence of helpers. Offspring from helped nests are heavier and more
      likely to recruit into the breeding population, thus helpers gain indirect
      fitness benefits from increasing the productivity of the current breeding
      attempt. Despite breeders' reduction of feeding effort in the presence of
      helpers, previous investigations found no subsequent increase in breeder
      survival. 3. The aim of this study was to test the hypothesis that load
      lightening resulted in indirect fitness benefits for helpers. We used data from a
      14-year study to investigate the provisioning rate, survival and future fecundity
      of male and female long-tailed tits that did and did not receive help at the
      nest. 4. We found an asymmetrical response to the presence of helpers at large
      brood sizes. Males reduced their feeding rate more than females, and this
      differential response was reflected in a significant increase in male survival
      when provisioning large broods assisted by helpers. We found no evidence of any
      increase in future fecundity for helped breeders. 5. The finding that males
      reduce their provisioning rate in the presence of helpers (at large brood sizes)
      to a greater degree than females, and that this is reflected in an increase in
      survival rate for males only, implies that the survival increase is caused by the
      reduction in work-rate rather than a non-specific benefit of a larger group size.
      6. The marginal benefits of help for breeder survival are likely to be more
      difficult to identify than the increased productivity at helped nests, but should
      not be overlooked when investigating the potential indirect fitness gains that
      supernumeraries can accrue by helping.

PMID- 20132372
TI  - Culturable bacteria from Zn- and Cd-accumulating Salix caprea with differential
      effects on plant growth and heavy metal availability.
AB  - AIMS: To characterize bacteria associated with Zn/Cd-accumulating Salix caprea
      regarding their potential to support heavy metal phytoextraction. METHODS AND
      RESULTS: Three different media allowed the isolation of 44 rhizosphere strains
      and 44 endophytes, resistant to Zn/Cd and mostly affiliated with Proteobacteria,
      Actinobacteria and Bacteroidetes/Chlorobi. 1-Aminocyclopropane-1-carboxylic acid
      deaminase (ACCD), indole acetic acid and siderophore production were detected in
      41, 23 and 50% of the rhizosphere isolates and in 9, 55 and 2% of the endophytes,
      respectively. Fifteen rhizosphere bacteria and five endophytes were further
      tested for the production of metal-mobilizing metabolites by extracting
      contaminated soil with filtrates from liquid cultures. Four Actinobacteria
      mobilized Zn and/or Cd. The other strains immobilized Cd or both metals. An ACCD-
      and siderophore-producing, Zn/Cd-immobilizing rhizosphere isolate (Burkholderia
      sp.) and a Zn/Cd-mobilizing Actinobacterium endophyte were inoculated onto S.
      caprea. The rhizosphere isolate reduced metal uptake in roots, whereas the
      endophyte enhanced metal accumulation in leaves. Plant growth was not promoted.
      CONCLUSIONS: Metal mobilization experiments predicted bacterial effects on S.
      caprea more reliably than standard tests for plant growth-promoting activities.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteria, particularly Actinobacteria,
      associated with heavy metal-accumulating Salix have the potential to increase
      metal uptake, which can be predicted by mobilization experiments and may be
      applicable in phytoremediation.

PMID- 20132373
TI  - Generation of a mutagenized organophosphorus hydrolase for the biodegradation of
      the organophosphate pesticides malathion and demeton-S.
AB  - AIMS: The bacterial organophosphorus hydrolase (OPH) enzyme hydrolyses and
      detoxifies a broad range of toxic organophosphate pesticides and warfare nerve
      agents by cleaving the various phosphorus-ester bonds (P-O, P-F, P-CN, P-S);
      however, OPH hydrolyses these bonds with varying efficiencies. The aim of this
      study was to generate a variant OPH enzyme with improved hydrolytic efficiency
      against the poorly hydrolysed P-S class of organophosphates. METHODS AND RESULTS:
      The gene encoding OPH was sequentially mutated at specific codons by saturation
      mutagenesis and screened for improved activity against the P-S substrates demeton
      S methyl and malathion. Escherichia coli lysates harbouring the variants
      displayed up to 177- and 1800-fold improvement in specific activity against
      demeton-S methyl and malathion, respectively, compared to the wild-type lysates.
      The specificity constants of the purified variant proteins were improved up to 25
      fold for demeton-S methyl and malathion compared to the wild-type. Activity was
      associated with organophosphate detoxification as the hydrolysed substrate lost
      the ability to inhibit acetylcholinesterase. The improved hydrolytic efficiency
      against demeton-S translated to the improved ability to hydrolyse the warfare
      agent VX. CONCLUSIONS: OPH variant enzymes were generated that displayed
      significantly improved ability to hydrolyse and detoxify organophosphates
      harbouring the P-S bond. SIGNIFICANCE AND IMPACT OF THE STUDY: The long-term goal
      is to generate an environmentally-friendly enzyme-mediated bioremediation
      approach for the removal of toxic organophosphate compounds in the environment.

PMID- 20132374
TI  - Phage-selected lipopolysaccharide mutants of Pectobacterium atrosepticum exhibit
      different impacts on virulence.
AB  - AIMS: To positively select Pectobacterium atrosepticum (Pa) mutants with cell
      surface defects and to assess the impact of these mutations on phytopathogenesis.
      METHODS AND RESULTS: Several phages were isolated from treated sewage effluent
      and were found to require bacterial lipopolysaccharide (LPS) for infection. Two
      strains with distinct mutations in LPS were obtained by transposon mutagenesis.
      Along with a third LPS mutant, these strains were characterized with respect to
      various virulence-associated phenotypes, including growth rate, motility and
      exoenzyme production, demonstrating that LPS mutations are pleiotropic. Two of
      the strains were deficient in the synthesis of the O-antigen portion of LPS, and
      both were less virulent than the wild type. A waaJ mutant, which has severe
      defects in LPS biosynthesis, was dramatically impaired in potato tuber rot
      assays. The infectivity of these novel phages on 32 additional strains of Pa was
      tested, showing that most Pa isolates were sensitive to the LPS-dependent phages.
      CONCLUSIONS: Native LPS is crucial for optimal growth, survival and virulence of
      Pa in vivo, but simultaneously renders such strains susceptible to phage
      infection. SIGNIFICANCE AND IMPACT OF THE STUDY: This work demonstrates the power
      of phages to select and identify the virulence determinants on the bacterial
      surface, and as potential biocontrol agents for Pa infections.

PMID- 20132375
TI  - Enterococcus species distribution among human and animal hosts using multiplex
      PCR.
AB  - AIMS: This study evaluated the use of Enterococcus species differentiation as a
      tool for microbial source tracking (MST) in recreational waters. METHODS AND
      RESULTS: Avian, mammalian and human faecal samples were screened for the
      occurrence of Enterococcus avium, Enterococcus casseliflavus, Enterococcus
      durans, Enterococcus gallinarum, Enterococcus faecium, Enterococcus faecalis,
      Enterococcus hirae and Enterococcus saccharolyticus using multiplex PCR. Host
      specific patterns of Enterococcus species presence were observed only when data
      for multiple Enterococcus species were considered in aggregate. CONCLUSIONS: The
      results suggest that no single Enterococcus species is a reliable indicator of
      the host faecal source. However, Enterococcus species composite 'fingerprints'
      may offer auxiliary evidence for bacterial source identification. SIGNIFICANCE
      AND IMPACT OF STUDY: This study presents novel information on the enterococci
      species assemblages present in avian and mammalian hosts proximate to the
      nearshore ocean. These data will aid the development of appropriate MST
      strategies, and the approach used in this study could potentially assist in the
      identification of faecal pollution sources.

PMID- 20132376
TI  - Effects of initial inoculation density of Paenibacillus polymyxa on colony
      formation and starch-hydrolytic activity in relation to root rot in ginseng.
AB  - AIMS: To examine the relationships between population growth and biological
      characters of the plant-growth-promoting rhizobacterium Paenibacillus polymyxa
      GBR-1. METHODS AND RESULTS: Population growth, colony formation, starch
      hydrolytic activity, and ginseng root rot caused by P. polymyxa GBR-1 isolated
      from a rotten ginseng root were examined in vitro and in vivo at high [1 x 10(8)
      colony-forming units (CFU) ml(-1)] and low (1 x 10(6) CFU ml(-1)) initial
      inoculum densities. Paenibacillus polymyxa GBR-1 showed strong starch-hydrolytic
      activity on modified starch agar with relatively low starch content, but only at
      certain incubation temperatures (18 and 23 degrees C); the high-density inoculum
      produced bacterial colonies about nine times thicker than those formed from the
      lower inoculum density. Light, scanning electron, and transmission electron
      microscopy showed that the thick colonies from the high-density inoculum were
      filled with extracellular polymeric substances (EPS), in which a relatively small
      number of ovoid-rod-shaped bacterial cells (mostly endospore-bearing cells) were
      distributed. In contrast, the thin colonies from the low-density inoculum were
      composed of massive vegetative cells with a rectangular rod shape and minimum
      EPS. Fluorescent in situ hybridization (FISH) revealed that the beta-amylase gene
      was expressed only in bacterial cells from the thick colonies formed from the
      high-density inoculum, but not in those from the low-density inoculum. The
      culture filtrate from the thick colonies produced a hydrolytic clear zone on
      modified starch agar, degraded starch granules in various manners, and produced
      rot symptoms on ginseng root tissues. CONCLUSIONS: The biological properties of
      colony formation, starch hydrolysis, and ginseng tissue rotting by P. polymyxa
      GBR-1 are interrelated; they are influenced by the initial bacterial population
      density but not by the in situ and the final population densities. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Knowledge of disease-inducing characters of P. polymyxa
      GBR-1 can be used in the development of biocontrol strategies.

PMID- 20132377
TI  - Ventricular tachycardia ablation: what have we learned from SMASH-VT.

PMID- 20132378
TI  - Implantable cardioverter-defibrillator in patients with hypertrophic
      cardiomyopathy: efficacy and complications of the therapy in long-term follow-up.
AB  - INTRODUCTION: Although implantable cardioverter-defibrillators (ICDs) are used in
      sudden cardiac death (SCD) prevention in high-risk patients with hypertrophic
      cardiomyopathy (HCM), long-term results as well as precise risk stratification
      are discussed in a limited number of reports. The aim of the study was to assess
      the incidence of ICD intervention in HCM patients with relation to clinical risk
      profile. METHODS AND RESULTS: We studied 104 consecutive patients with HCM
      implanted in a single center. The mean age of study population was 35.6 (SD,
      16.2) years with the average follow-up of 4.6 (SD, 2.6) years. ICD was implanted
      for secondary (n = 26) and primary (n = 78) prevention of SCD. In the secondary
      prevention group, 14 patients (53.8%) experienced at least 1 appropriate device
      intervention (7.9%/year). In the primary prevention (PP) group appropriate ICD
      discharges occurred in 13 patients (16.7%) and intervention rate was 4.0%/year.
      Nonsustained VT was the only predictive risk factor (RF) for an appropriate ICD
      intervention in the PP (positive predictive value 22%, negative predictive value
      96%). No significant difference was observed in the incidence of appropriate ICD
      discharges between PP patients with 1, 2, or more RF. Complications of the
      treatment included: inappropriate shocks (33.7%), lead dysfunction (12.5%), and
      infections: 4.8% of patients. Four patients died during follow-up. CONCLUSION:
      ICD therapy is effective in SCD prevention in patients with HCM, although the
      complication rate is significant. Nonsustained ventricular tachycardia seems to
      be the most predictive RF for appropriate device discharges. Number of RF did not
      impact the incidence of appropriate ICD interventions.

PMID- 20132379
TI  - Atrial tachycardia confined within the left atrial appendage.
AB  - Left atrial tachycardias are often seen following catheter ablation of persistent
      atrial fibrillation (AF). We report here an unusual case where AF was converted
      to sinus rhythm following catheter ablation, but ongoing atrial tachycardia
      confined within the left atrial appendage (LAA) was observed. Although the LAA
      tachycardia was dissociated from the atrium in sinus rhythm, bidirectional
      conduction between the left atrium and the LAA was, however, demonstrated after
      tachycardia termination.

PMID- 20132380
TI  - The surface electrocardiogram predicts risk of heart block during right heart
      catheterization in patients with preexisting left bundle branch block:
      implications for the definition of complete left bundle branch block.
AB  - BACKGROUND: Patients with left bundle branch block (LBBB) undergoing right heart
      catheterization can develop complete heart block (CHB) or right bundle branch
      block (RBBB) in response to right bundle branch (RBB) trauma. We hypothesized
      that LBBB patients with an initial r wave (>or=1 mm) in lead V1 have intact left
      to right ventricular septal (VS) activation suggesting persistent conduction over
      the left bundle branch. Trauma to the RBB should result in RBBB pattern rather
      than CHB in such patients. METHODS: Between January 2002 and February 2007, we
      prospectively evaluated 27 consecutive patients with LBBB developing either CHB
      or RBBB during right heart catheterization. The prevalence of an r wave >or=1 mm
      in lead V1 was determined using 118 serial LBBB electrocardiographs (ECGs) from
      our hospital database. RESULTS: Catheter trauma to the RBB resulted in CHB in 18
      patients and RBBB in 9 patients. All 6 patients with >or=1 mm r wave in V1
      developed RBBB. Among these 6 patients q wave in lead I, V5, or V6 were present
      in 3. Four patients (3 in CHB group and 1 in RBBB group) developed spontaneous
      CHB during a median follow-up of 61 months. V1 q wave >or=1 mm was present in 28%
      of hospitalized complete LBBB patients. CONCLUSIONS: An initial r wave of >or=1
      mm in lead V1 suggests intact left to right VS activation and identifies LBBB
      patients at low risk of CHB during right heart catheterization. These preliminary
      findings indicate that an initial r wave of >or=1 mm in lead V1, present in
      approximately 28% of ECGs with classically defined LBBB, may constitute a new
      exclusion criterion when defining complete LBBB.

PMID- 20132381
TI  - Reduction of ventricular sodium current in a mouse model of HIV.
AB  - INTRODUCTION: Cardiac arrhythmias have been reported in AIDS patients.
      Arrhythmias can arise from alterations in ventricular Na(+) channel function.
      However, it is unknown whether HIV affects cardiac Na(+) channel function.
      Therefore, the purpose of this study was to characterize the effect of HIV on
      ventricular Na(+) current (I(Na)) in a transgenic model of HIV (CD4C/HIV mice),
      which exhibit a severe AIDS-like disease. METHODS AND RESULTS: Patch-clamp
      techniques were used to examine I(Na) and action potentials (AP) in ventricular
      myocytes isolated from HIV and wild-type (WT) mice. In HIV myocytes peak I(Na)
      was reduced (at -50 mV: HIV, -55.3 +/- 4.3 pA/pF, n = 15; WT, -79.4 +/- 5.2
      pA/pF, n = 16, P < 0.05), whereas late I(Na) was similar in both groups (HIV, 
      4.3 +/- 0.4 pA/pF; WT, -4.4 +/- 0.4 pA/pF, n = 22/group). AP amplitude (HIV 91.5
      +/- 4.7 mV, n = 12; WT 104.4 +/- 3.1 mV, n = 15, P < 0.05) and the maximal
      velocity of the AP upstroke (V(max); HIV, 57.2 +/- 9.3 mV/ms, n = 12; WT, 113.5
      +/- 8 mV/ms, n = 15, P < 0.05) were decreased in HIV myocytes. ECG recordings
      revealed that the QRS complex was prolonged in HIV mice (HIV, 15.7 +/- 0.2 ms, n
      = 22; WT, 14.1 +/- 0.5 ms, n = 10, P < 0.05). The serum levels of interleukin
      1beta were elevated in HIV mice (HIV, 18.1 +/- 3.1 pg/mL, n = 3; WT, 5.1 +/- 1.1
      pg/mL, n = 4, P < 0.05) in line with previous evidence that suggests that
      elevated levels of cytokines can affect cardiac ion currents. CONCLUSION:
      Overall, our observations suggest that elevated levels of proinflammatory
      cytokines in CD4C/HIV mice could alter Na(+) channel function, thus altering
      cardiac depolarization and contribute to the generation of arrhythmias.

PMID- 20132382
TI  - Impact of pharmacological autonomic blockade on complex fractionated atrial
      electrograms.
AB  - INTRODUCTION: The influence of the autonomic nervous system on the pathogenesis
      of complex fractionated atrial electrograms (CFAE) during atrial fibrillation
      (AF) is incompletely understood. This study evaluated the impact of
      pharmacological autonomic blockade on CFAE characteristics. METHODS AND RESULTS:
      Autonomic blockade was achieved with propanolol and atropine in 29 patients
      during AF. Three-dimensional maps of the fractionation degree were made before
      and after autonomic blockade using the Ensite Navx system. In 2 patients, AF
      terminated following autonomic blockade. In the remaining 27 patients, 20,113
      electrogram samples of 5 seconds duration were collected randomly throughout the
      left atrium (10,054 at baseline and 10,059 after autonomic blockade). The impact
      of autonomic blockade on fractionation was assessed by blinded investigators and
      related to the type of AF and AF cycle length. Globally, CFAE as a proportion of
      all atrial electrogram samples were reduced after autonomic blockade: 61.6 +/-
      20.3% versus 57.9 +/- 23.7%, P = 0.027. This was true/significant for paroxysmal
      AF (47 +/- 23% vs 40 +/- 22%, P = 0.003), but not for persistent AF (65 +/- 22%
      vs 62 +/- 25%, respectively, P = 0.166). Left atrial AF cycle length prolonged
      with autonomic blockade from 170 +/- 33 ms to 180 +/- 40 ms (P = 0.001).
      Fractionation decreases only in the 14 of 27 patients with a significant (>6 ms)
      prolongation of the AF cycle length (64 +/- 20% vs 59 +/- 24%, P = 0.027),
      whereas fractionation did not reduce when autonomic blockade did not affect the
      AF cycle length (58 +/- 21% vs 56 +/- 25%, P = 0.419). CONCLUSIONS:
      Pharmacological autonomic blockade reduces CFAE in paroxysmal AF, but not
      persistent AF. This effect appears to be mediated by prolongation of the AF cycle
      length.

PMID- 20132383
TI  - Right coronary artery occlusion during RF ablation of typical atrial flutter.
AB  - Right coronary artery (RCA) occlusion and acute myocardial infarction are rare
      during radiofrequency (RF) ablation of the cavotricuspid isthmus. Ventricular
      fibrillation (VF) or cardiac arrest in the periprocedural period may be the
      initial or only clinical manifestation. Septal or lateral RF delivery may
      increase the risk. We report 2 cases of RCA occlusion during ablation of typical
      atrial flutter (AFL). Angiographic and anatomical correlations are illustrated.
      One patient was ablated with a septal approach, the other with a lateral
      approach, and in each instance the RCA occluded near the ablative lesions. If
      septal or lateral ablation lines are contemplated during ablation of isthmus
      dependent atrial flutter, fluoroscopic or electroanatomic confirmation of
      catheter position is pivotal. Smaller tipped catheters, energy titration (to
      minimally effective dose), saline irrigation, or cryoablation should also be
      considered to help avoid this serious complication.

PMID- 20132384
TI  - Macrovolt T-wave alternans in an asymptomatic woman with long-QT syndrome: a rare
      but clinically significant finding.

PMID- 20132385
TI  - Higher rate of recurrent atrial flutter and atrial fibrillation following atrial
      flutter ablation after cardiac surgery.
AB  - INTRODUCTION: Atrial flutter (AFL) is common after cardiac surgery. However, the
      types of post-cardiac surgery AFL, its response to catheter-based radiofrequency
      ablation, and its relationship to atrial fibrillation (AF) are unknown. METHODS
      AND RESULTS: We retrospectively studied all patients who underwent mapping and
      ablation for AFL after cardiac surgery from January 1990 to July 2004. One
      hundred randomly selected patients without prior cardiac surgery (PCS) who
      underwent mapping and ablation of AFL served as the control population. A total
      of 236 patients formed the study population (mean age 62 + 13 years, 22% female)
      and 100 patients formed the control population (mean age 60 + 13 years, 25%
      female). The majority of patients without PCS had cavo-tricuspid isthmus (CTI)
      dependent AFL when compared to patients with PCS (93% vs 72%, respectively, P <
      0.0001). In contrast, scar-related AFL was more common in patients with PCS as
      compared to patients without PCS (22% vs 3%, P < 0.0001). Predictors of scar
      related AFL in multivariable regression analysis included PCS and left-sided AFL.
      Acute success rates and complications were similar between the groups. When
      compared to patients with AFL ablation without PCS, those that had AFL after PCS
      had higher rates of recurrence of both AFL (1% vs 12%, P < 0.0001; mean time to
      recurrence 1.85 years) and AF (16% vs 28%, P = 0.02; mean time to recurrence 2.67
      years). CONCLUSION: Despite ablation of AFL, patients with PCS have a higher rate
      of AFL and AF when compared to patients without PCS who underwent ablation of
      atrial flutter during long-term follow-up.

PMID- 20132386
TI  - Role of the transient outward current in regulating mechanical properties of
      canine ventricular myocytes.
AB  - INTRODUCTION: The transient outward current (I(to)) is a major repolarizing
      current in the heart. Reduction of I(to) density is consistently observed in
      human heart failure (HF) and animal HF models. It has been proposed that I(to),
      via its influence on phase-1 repolarization of the action potential, facilitates
      L-type Ca(2+) current (I(Ca-L)) activation and sarcoplasmic reticulum Ca(2+)
      release, and that its down-regulation may contribute to the impaired
      contractility in failing heart. METHODS AND RESULTS: We used the dynamic clamp to
      quantitatively examine the influence of I(to) on the mechanical properties of
      canine left ventricular myocytes at 34 degrees C. In endocardial myocytes, where
      the native I(to) is small, simulation of an epicardial-level artificial I(to)
      accentuated the phase-1 repolarization and significantly suppressed cell
      shortening. The peak amplitude of Ca(2+) transient was also reduced in the
      presence of simulated I(to), although the rate of rise of the Ca(2+) transient
      was increased. Conversely, subtraction, or "blockade" of the native I(to)
      enhanced contractility in epicardial cells. These results agree with the inverse
      correlation between I(to) levels and myocyte contractility and Ca(2+) transient
      amplitude in epicardial and endocardial myocytes. Action potential clamp studies
      showed that the phase-1 repolarization/I(to) versus I(Ca-L) relationship had an
      inverted-J shape; small I(to) enhanced peak I(Ca-L) while moderate-to-large I(to)
      decreased peak I(Ca-L) and markedly reduced early Ca(2+) influx. CONCLUSION: Our
      results show that epicardial-level of I(to) acts as a negative, rather than
      positive regulator of myocyte mechanical properties in canine ventricular
      myocytes.

PMID- 20132387
TI  - Nodoventricular pathway associated with twin AV nodes: complexity of ablation in
      single ventricle physiology.
AB  - We report the case of a patient with heterotaxy syndrome including complex single
      ventricular morphology and interrupted IVC in association with twin conduction
      systems and a nodoventricular accessory pathway connection. The presence of 3
      distinct QRS morphologies was inadvertently discovered during a hemodynamic
      catheterization study and prompted formal EP testing prior to hepatic venous
      inclusion into the Fontan circuit and loss of access to the atrial chamber for
      testing and therapy. This patient underscores the importance of close
      surveillance and high index of suspicion of arrhythmia mechanisms in patients
      with heterotaxy syndrome in conjunction with single ventricle morphology.

PMID- 20132388
TI  - Optimizing survival from out-of-hospital cardiac arrest.
AB  - Cardiac arrest is an important public health problem and often occurs in the out
      of-hospital setting in patients without a prior history of heart disease. Very
      few communities or emergency medical service (EMS) systems report survival rates
      for out-of-hospital cardiac arrest. Among those who do, survival rates vary
      substantially between cities, due in large part to community differences in the
      chain of survival. To improve survival in cardiac arrest, care must be optimized
      at each point along the cardiac arrest continuum, including a rapid emergency
      response, provision of cardiopulmonary resuscitation (CPR) by bystanders,
      delivery of high-quality chest compressions with minimal interruptions by first
      responders, rapid defibrillation, and optimization of postresuscitation care,
      including therapeutic hypothermia. Important current initiatives to improve
      cardiac arrest survival include hands-only CPR delivered by laypersons prior to
      the arrival of EMS, dispatcher-assisted CPR, and implementation of hospital-based
      therapeutic hypothermia protocols to improve postresuscitation care. Optimizing
      cardiac arrest survival requires a team effort between EMS directors, emergency
      physicians, cardiologists, hospital leadership, and the public.

PMID- 20132389
TI  - Influence of clinical and procedural predictors on ventricular tachycardia
      ablation outcomes: an analysis from the substrate mapping and ablation in Sinus
      Rhythm to Halt Ventricular Tachycardia Trial (SMASH-VT).
AB  - BACKGROUND: The Substrate Mapping and Ablation in Sinus Rhythm to Halt
      Ventricular Tachycardia (SMASH-VT) trial is the largest randomized trial in
      substrate-based ablation. We performed a retrospective analysis of patients
      randomized to prophylactic ablation of ventricular tachycardia to determine the
      predictive value of clinical and procedural variables on outcomes. METHODS: In
      patients treated with catheter ablation, we examined predictors of ICD-therapy
      free survival using Cox proportional hazards models. Procedural variables tested
      included the scar location, number of VT morphologies (VTs) induced, tachycardia
      cycle length, catheter irrigation, catheter approach, procedural duration, and VT
      inducibility after ablation. Clinical variables including age, index arrhythmia,
      NYHA class, ejection fraction, prior revascularization, and baseline medication
      use were also analyzed. RESULTS: Among 64 patients randomized to ablation, 61
      received the assigned therapy and complete procedural data were available for 54
      patients. Thirteen percent (7 of 54) experienced ICD therapies during 2-year
      follow-up. Patients with subsequent ICD therapies had significantly more VTs
      induced during the ablation procedure than those without (3.9 +/- 2.1 vs 1.9 +/-
      1.8, P = 0.05). The hazard ratio for each additional VT induced was 1.51 (95% CI
      1.07-2.13, P = 0.02). Two-year Kaplan-Meier event-free survival rates were 96%
      for 0-1 VTs induced, and 78% for two or more. The use of irrigated catheters was
      not predictive of ablation success. CONCLUSION: In this small retrospective
      analysis, the number of VTs induced during the procedure was predictive of 2-year
      outcomes. This likely reflects a more complex arrhythmia substrate in patients
      who fail ablation.

PMID- 20132390
TI  - Bradycardiomyopathy: the case for a causative relationship between severe sinus
      bradycardia and heart failure.
AB  - A 28-year-old man presented with progressive fatigue. Physical examination and
      ECG revealed severe sinus bradycardia. Echocardiography showed features of
      noncompaction cardiomyopathy and moderate aortic valve regurgitation. We
      hypothesized that the chronic volume overload exaggerated by prolonged diastole
      due to the bradycardia resulted in heart failure and noncompaction cardiomyopathy
      look-alike features. After implantation of an AAI pacemaker, his symptoms and
      signs of cardiomyopathy were fully recovered.

PMID- 20132391
TI  - The permanency of pulmonary vein isolation using a balloon cryoablation catheter.
AB  - BACKGROUND: Because of its technical feasibility and presumed safety benefits,
      balloon cryoablation is being increasingly employed for pulmonary vein (PV)
      isolation. While acute isolation has been demonstrated in most patients, little
      data are available on the chronic durability of cryoballoon lesions. METHODS AND
      RESULTS: Twelve atrial fibrillation patients underwent PV isolation using either
      a 23-mm or 28-mm cryoballoon. For each vein, after electrical isolation was
      verified with the use of a circular mapping cathether, 2 bonus balloon ablation
      lesions were placed. Gaps in balloon occlusion were overcome using either a spot
      cryocatheter or a "pull-down" technique. A prespecified second procedure was
      performed at 8-12 weeks to assess for long-term PV isolation. Acute PV isolation
      was achieved in all PVs in the patient cohort (n = 48 PVs), using the cryoballoon
      alone in 47/48 PVs (98%); a "pull-down" technique was employed for 5 PVs (1 right
      superior pulmonary vein, 2 right inferior pulmonary veins, and 2 left inferior
      pulmonary veins). The gap in the remaining vein was ablated with a spot
      cryocatheter. During the second mapping procedure, 42 of 48 PVs (88%) remained
      isolated. One vein had reconnected in 2 patients, while 2 veins had reconnected
      in another 2 patients. All PVs initially isolated with the "pull-down" technique
      remained isolated at the second procedure. CONCLUSIONS: Cryoballoon ablation
      allows for durable PV isolation with the use of a single balloon. With maintained
      chronic isolation in most PVs, it may represent a significant step toward
      consistent and lasting ablation procedures.

PMID- 20132392
TI  - Disorders of the autonomic nervous system in patients with Brugada syndrome: a
      pilot study.
AB  - INTRODUCTION: The aim of this study was to examine autonomic disorders in
      patients with Brugada syndrome by performing a cardiac sympathetic innervation
      evaluation, a head-up tilt-test (HUT) and heart rate variability (HRV) analysis.
      METHODS AND RESULTS: We enrolled 20 patients with Brugada syndrome (mean age 42.5
      +/- 8.8 years), 9 with spontaneous and 11 with an induced type 1
      electrocardiogram (ECG) in the setting of symptoms and 20 age-matched controls.
      All subjects underwent a HUT with parallel measurements of plasma catecholamines
      and cortisol, a (123)I-metaiodobenzylguanidine single photon emission tomography,
      and HRV evaluation. Ten control subjects participated in the innervation portion
      of the study. The tilt-test with clomipramine challenge was positive in 15 of 20
      (75%) patients (7 spontaneous, 8 induced) and in 1 in controls (P < 0.01). A
      sympathoadrenal imbalance was shown in positive tests. The pattern of innervation
      in all groups was heterogenic and similar to controls with a trend towards lower
      measurements in patients with a spontaneous type 1 ECG and a positive HUT. HRV
      analysis did not reveal any significant differences during day and night. Four
      patients (20%) had sustained ventricular arrhythmias during a follow-up of 31.1
      +/- 8.6 months, but no correlations with innervation or response to tilting were
      found. CONCLUSION: A high susceptibility to vasovagal syncope was observed in
      patients with Brugada syndrome, which could be disease-related symptoms.
      Conversely, sympathetic innervation was observed to follow a physiological,
      heterogenic pattern; however, these factors did not have prognostic value for
      life-threatening arrhythmias.

PMID- 20132393
TI  - Ablation of paroxysmal atrial fibrillation: looking for the simple answer.

PMID- 20132394
TI  - Pseudoatrial fibrillation.

PMID- 20132395
TI  - Long-term outcome following successful catheter ablation of atrial tachycardia
      originating from the pulmonary veins: absence of late atrial fibrillation.
AB  - OBJECTIVES: This study aimed to characterize the long-term outcome and incidence
      of atrial fibrillation (AF) in patients following catheter ablation of focal
      atrial tachycardia (AT) from the pulmonary veins (PV). BACKGROUND: Although both
      AT and AF may originate from ectopic foci within PVs, it is unknown whether PV AT
      patients subsequently develop AF. METHODS: Twenty-eight patients with 29 PV ATs
      (14%) from a consecutive series of 194 patients who underwent RFA for focal AT
      were included. Patients with concomitant AF prior to the index procedure were
      excluded. RESULTS: The minimum follow-up duration was 4 years; mean age 38 +/- 18
      years with symptoms for 6.5 +/- 10 years, having tried 1.5 +/- 0.9 antiarrhythmic
      drugs. The distribution of foci was: left superior 12 (41%), right superior 10
      (34%), left inferior 5 (17%), and right inferior 2 (7%). The focus was ostial in
      93% and 2-4 cm distally within the vein in 7%. Mean tachycardia cycle length was
      364 +/- 90 ms. Focal ablation was performed in 25 of 28 patients. There were 6
      recurrences with 5 from the original site. Twenty-six patients were available for
      long-term clinical follow-up. At a mean of 7.2 +/- 2.1 years, 25 of 26 (96%) were
      free from recurrence off antiarrhythmic drugs. No patients developed AF.
      CONCLUSIONS: Focal ablation for tachycardia originating from the PVs is
      associated with long-term freedom from both AT and AF. Therefore, although PV AT
      and PV AF share a common anatomic distribution, PV AT is a distinct clinical
      entity successfully treated with focal RFA and not associated with AF in the long
      term.

PMID- 20132396
TI  - Mapping of atrial tachycardia by remote magnetic navigation in postoperative
      patients with congenital heart disease.
AB  - OBJECTIVES: The purpose of this study was to investigate if remote magnetic
      navigation (RMN) offers a reduction of fluoroscopy time when used for atrial
      tachycardia (AT) mapping in a spectrum of patients with congenital heart disease
      (CHD) after "simple" or "complex" atrial surgery. BACKGROUND: Data about AT
      mapping using RMN in larger populations of patients with CHD are scarce. METHODS:
      RMN in combination with electroanatomic mapping was used for AT mapping in 22
      patients. According to anatomic complexity, patients were classified into 3
      groups: Group 1: patients after minor atrial surgery (n = 7); Group 2: patients
      after the Fontan operation (n = 9); and group 3: patients after the
      Senning/Mustard operation (n = 6). RESULTS: Atrial mapping with a nonirrigated
      tip RMN catheter was completed successfully in all patients. In Group 1 no
      significant reduction in fluoroscopy time was noticed over time (mean fluoroscopy
      time 7.9 minutes). In the 15 patients of group 2 and group 3 with complex CHD,
      the fluoroscopy time for mapping in the last 9 patients (6.4 +/- 2.8 minutes) was
      significantly shorter than in the first 6 patients (29.7 +/- 10.5 minutes, P <
      0.0001). Acutely successful ablation was achieved in 21 of 22 patients (97%)
      using the RMN catheter (n = 3) or a conventional catheter (n = 18) without
      procedural complications. CONCLUSIONS: RMN for AT mapping in patients with
      complex atrial anatomy leads to a significant reduction of fluoroscopy time.

PMID- 20132397
TI  - Optimal timing of implantable cardioverter-defibrillator implantation after
      myocardial infarction: a decision analysis.
AB  - BACKGROUND: The optimal timing of implantable cardioverter defibrillator (ICD)
      placement for the primary prevention of sudden cardiac death after myocardial
      infarction (MI) remains unknown. METHODS AND RESULTS: We developed a Markov model
      to investigate the optimal timing of ICD implantation after MI (no ICD, ICD at 60
      days, 6 months, and 1 year) in patients who meet current guidelines. Estimates of
      arrhythmic death (baseline risk 6%, range 1-20% per year), nonarrhythmic death,
      and ICD efficacy were based upon MADIT-II and other contemporary post-MI clinical
      trials. We used both deterministic and stochastic modeling processes in our
      analysis. After 10 years follow-up, the baseline probability of survival was
      higher in those treated with ICD implantation versus not (42% vs 30%, P < 0.001).
      Survival was highest with ICD implantation at 60 days versus 6 months versus 1
      year: 42.4%, 42.3%, and 42.0% (P = 0.0028). ICD implantation at 60 days provided
      a mean incremental survival of 0.28 months and 0.84 months per patient (compared
      with implantation at 6 months and 1 year). In sensitivity analyses, patients'
      competing risk for nonarrhythmic death was the primary determinant of benefit
      from ICD implantation. Overall, ICD implantation at 60 days resulted in the
      greatest life expectancy over a wide range of plausible nonarrhythmic and
      arrhythmic death rates. CONCLUSIONS: The benefits of early ICD implantation are
      modest when compared with delayed implantation at 6 months/1 year. Our results
      suggest that making sure a patient receives an ICD, when appropriate, may be more
      important than the timing of the implantation procedure.

PMID- 20132398
TI  - Measuring the complexity of atrial fibrillation electrograms.
AB  - INTRODUCTION: Complex fractionated atrial electrograms (CFAE) have been
      identified as targets for atrial fibrillation (AF) ablation. Robust automatic
      algorithms to objectively classify these signals would be useful. The aim of this
      study was to evaluate Shannon's entropy (ShEn) and the Kolmogorov-Smirnov (K-S)
      test as a measure of signal complexity and to compare these measures with
      fractional intervals (FI) in distinguishing CFAE from non-CFAE signals. METHODS
      AND RESULTS: Electrogram recordings of 5 seconds obtained from multiple atrial
      sites in 13 patients (11 M, 58 +/- 10 years old) undergoing AF ablation were
      visually examined by 4 independent reviewers. Electrograms were classified as
      CFAE if they met Nademanee criteria. Agreement of 3 or more reviewers was
      considered consensus and the resulting classification was used as the gold
      standard. A total of 297 recordings were examined. Of these, 107 were consensus
      CFAE, 111 were non-CFAE, and 79 were equivocal or noninterpretable. FIs less than
      120 ms identified CFAEs with sensitivity of 87% and specificity of 79%. ShEn,
      with optimal parameters using receiver-operator characteristic curves, resulted
      in a sensitivity of 87% and specificity of 81% in identifying CFAE. The K-S test
      resulted in an optimal sensitivity of 100% and specificity of 95% in classifying
      uninterpretable electrogram from all other electrograms. CONCLUSIONS: ShEn showed
      comparable results to FI in distinguishing CFAE from non-CFAE without requiring
      user input for threshold levels. Thus, measuring electrogram complexity using
      ShEn may have utility in objectively and automatically identifying CFAE sites for
      AF ablation.

PMID- 20132399
TI  - Ablation of ventricular arrhythmias in arrhythmogenic right ventricular
      dysplasia.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a genetically determined
      myocardial disease characterized by fibrofatty replacement of the right
      ventricular wall. Ventricular tachyarrhythmias can be seen in the early stages of
      the disease, which is one of the most important causes of sudden death in young
      healthy individuals. Radiofrequency (RF) catheter ablation is an option for the
      treatment of medically refractory ventricular arrhythmias and it has shown to
      successfully abolish recurrent ventricular tachycardias (VT) as well as reduce
      the frequency in defibrillator therapies. However, variable acute and long-term
      success rates have been reported. The current mapping and ablation techniques
      include activation and entrainment mapping during tolerated VT and substrate
      ablation using 3-dimensional electroanatomic mapping systems. This article aims
      at providing a comprehensive review of RF catheter ablation of ventricular
      arrhythmias in the context of ARVD.

PMID- 20132400
TI  - Importance of catheter contact force during irrigated radiofrequency ablation:
      evaluation in a porcine ex vivo model using a force-sensing catheter.
AB  - INTRODUCTION: Ablation electrode-tissue contact has been shown to be an important
      determinant of lesion size and safety during nonirrigated ablation but little
      data are available during irrigated ablation. We aimed to determine the
      importance of contact force during irrigated-tip ablation. METHODS AND RESULTS:
      Freshly excised hearts from 11 male pigs were perfused and superfused using
      fresh, heparinized, oxygenated swine blood in an ex vivo model. One-minute
      ablations were placed using one of 3 different power control strategies
      (impedance control-15 Omega target impedance drop, and 20 W or 30 W fixed power)
      and 3 different contact forces (2 g, 20 g, and 60 g) to give a grid of 9 ablation
      groups. The force sensing catheter (Tacticath, Endosense SA) was irrigated at 17
      mL/min for all of the ablations. Of a total 101 ablations, no thrombus formation
      was noted but popping was seen in 17 lesions. The lesion depth and incidence of
      pops was 5.0 +/- 1.3 mm /0%, 5.0 +/- 1.6 mm /10% and 6.7 +/- 2.5 mm /45% for the
      15 Omega, 20 W, and 30 W groups (P < 0.01), respectively, and 4.4 +/- 1.8 mm /3%,
      5.8 +/- 1.6 mm /17% and 6.6 +/- 2.0 mm /37% for the 2 g, 20 g, and 60 g groups,
      respectively (P < 0.01). The impedance drop in the first 5 seconds was
      significantly correlated to catheter contact force: 9.7 +/- 9.9 Omega, 22.3 +/-
      11.0 Omega, and 41.7 +/- 22.1 Omega, respectively, for the 2 g, 20 g, and 60 g
      groups (Pearson's r = 0.65, P < 0.01). CONCLUSION: Catheter contact force has an
      important impact on both ablation lesion size and the incidence of pops.

PMID- 20132401
TI  - Creating lesions and indexing transmural ablation: pushing harder to find the
      Holy Grail.

PMID- 20132402
TI  - A regular ventricular tachycardia with variable QRS morphologies originating from
      the interventricular septum: what is the mechanism?

PMID- 20132403
TI  - A "regular irregular" tachycardia: what is the mechanism?

PMID- 20132404
TI  - Comparative expression of proteins in left and right atrial appendages from
      patients with mitral valve disease at sinus rhythm and atrial fibrillation.
AB  - INTRODUCTION: The objective was to compare by proteomics the expression of
      proteins associated with the cytoskeleton, energetic metabolism, and cardiac
      cytoprotection between left atrial appendages (LAA) and right atrial appendages
      (RAA) obtained from patients with mitral valve disease both in sinus rhythm (SR,
      n = 6) and in permanent atrial fibrillation (AF, n = 11). METHODS AND RESULTS:
      Samples from RAA and LAA were obtained from the same patient. Proteins were
      separated in 2-dimensional electrophoresis and identified by mass spectrometry.
      LAA from SR patients upexpressed alpha-actin isotype 1 and desmin isotypes 3 and
      5 with respect to RAA. In LAA from AF patients were upexpressed cardiac alpha
      actin isotypes 1 and 2, tropomyosin alpha- and beta-chains, and myosin light
      chain embryonic muscle/atrial isoform with respect to LAA from SR patients. In
      RAA from AF patients also upexpressed different cytoskeleton associated proteins
      with respect to RAA from SR patients. Different energetic metabolism-associated
      proteins were upexpressed in LAA and RAA from AF with respect those from SR
      patients. In AF patients, the expression of proteins associated with cardiac
      cytoprotection such as gluthatione-S-transferase, heat shock protein (Hsp) 27,
      and different Hsp60 isotypes, were higher in RAA but not in LAA with respect to
      the corresponding appendages in SR patients. CONCLUSIONS: For each individual
      patient RAA and LAA showed a similar level of proteins expressed associated with
      cytoskeleton, energetic metabolism, and cardiac cytoprotection. There were more
      differences in the level of proteins associated with the above-mentioned
      mechanisms between the atrial appendages from AF with respect to SR patients,
      which may open new targets for drugs.

PMID- 20132405
TI  - Brain recovery--an unified theory.

PMID- 20132408
TI  - Characterization of smooth muscle differentiation of purified human skeletal
      muscle-derived cells.
AB  - The purpose of this study is to characterize the smooth muscle differentiation of
      purified human muscle-derived cells (hMDCs). The isolation and purification of
      hMDCs were conducted by modified preplate technique and Dynal CD34 cell
      selection. Smooth muscle cell differentiation was induced by the use of smooth
      muscle induction medium (SMIM) and low-serum medium. The gene expressions at the
      mRNA and protein levels of undifferentiated and differentiated hMDCs were tested
      by RT-PCR, Western blot and immunofluorescence studies. Western blot and
      immunofluorescence studies demonstrated the purified hMDCs cultured in SMIM for 4
      weeks and expressed significant amount of smooth muscle myosin heavy chain (MHC)
      and alpha-smooth muscle actin (ASMA). The cells cultured in low-serum medium for
      4 weeks also expressed ASMA, while the control group did not. RT-PCR analysis
      showed increased gene expression of smooth muscle markers, such as ASMA,
      Calponin, SM22, Caldesmon, Smoothelin and MHC when purified hMDCs were exposed to
      SMIM for 2 and 4 weeks when compared to the controls. In conclusion, we confirmed
      the smooth muscle differentiation capability of purified hMDCs. The gene
      expression of smooth muscle differentiation of purified hMDCs was characterized.
      These cells may be potential biomaterials for human tissue regeneration.

PMID- 20132407
TI  - Perspectives for the use of structural information and chemical genetics to
      develop inhibitors of Janus kinases.
AB  - Gain-of-function mutations in the genes encoding Janus kinases have been
      discovered in various haematologic diseases. Jaks are composed of a FERM domain,
      an SH2 domain, a pseudokinase domain and a kinase domain, and a complex interplay
      of the Jak domains is involved in regulation of catalytic activity and
      association to cytokine receptors. Most activating mutations are found in the
      pseudokinase domain. Here we present recently discovered mutations in the context
      of our structural models of the respective domains. We describe two structural
      hotspots in the pseudokinase domain of Jak2 that seem to be associated either to
      myeloproliferation or to lymphoblastic leukaemia, pointing at the involvement of
      distinct signalling complexes in these disease settings. The different domains of
      Jaks are discussed as potential drug targets. We present currently available
      inhibitors targeting Jaks and indicate structural differences in the kinase
      domains of the different Jaks that may be exploited in the development of
      specific inhibitors. Moreover, we discuss recent chemical genetic approaches
      which can be applied to Jaks to better understand the role of these kinases in
      their biological settings and as drug targets.

PMID- 20132409
TI  - Mechanisms in the loss of capillaries in systemic sclerosis: angiogenesis versus
      vasculogenesis.
AB  - Systemic sclerosis (SSc, scleroderma) is a chronic, multisystem connective tissue
      disorder affecting the skin and various internal organs. Although the disease is
      characterized by a triad of widespread microangiopathy, fibrosis and
      autoimmunity, increasing evidence indicates that vascular damage is a primary
      event in the pathogenesis of SSc. The progressive vascular injury includes
      persistent endothelial cell activation/damage and apoptosis, intimal thickening,
      delamination, vessel narrowing and obliteration. These profound vascular changes
      lead to vascular tone dysfunction and reduced capillary blood flow, with
      consequent tissue ischemia and severe clinical manifestations, such as digital
      ulceration or amputation, pulmonary arterial hypertension and scleroderma renal
      crisis. The resulting tissue hypoxia induces complex cellular and molecular
      mechanisms in the attempt to recover endothelial cell function and tissue
      perfusion. Nevertheless, in SSc patients there is no evidence of significant
      angiogenesis and the disease evolves towards chronic tissue ischemia, with
      progressive and irreversible structural changes in multiple vascular beds
      culminating in the loss of capillaries. A severe imbalance between pro-angiogenic
      and angiostatic factors may also lead to impaired angiogenic response during SSc.
      Besides insufficient angiogenesis, defective vasculogenesis with altered numbers
      and functional defects of bone marrow-derived endothelial progenitor cells may
      contribute to the vascular pathogenesis of SSc. The purpose of this article is to
      review the contribution of recent studies to the understanding of the complex
      mechanisms of impaired vascular repair in SSc. Indeed, understanding the
      pathophysiology of SSc-associated vascular disease may be the key in dissecting
      the disease pathogenesis and developing novel therapies. Either angiogenic or
      vasculogenic mechanisms may potentially become in the future the target of
      therapeutic strategies to promote capillary regeneration in SSc.

PMID- 20132410
TI  - Involvement of beta-adrenergic receptor in synaptic vesicle swelling and
      implication in neurotransmitter release.
AB  - Secretory vesicle swelling is required for vesicular discharge during cell
      secretion. The G(alphao) -mediated water channel aquaporin-6 (AQP-6) involvement
      in synaptic vesicle (SV) swelling in neurons has previously been reported.
      Studies demonstrate that in the presence of guanosine triphosphate (GTP),
      mastoparan, an amphiphilic tetradecapeptide from wasp venom, activates G(o)
      protein GTPase, and stimulates SV swelling. Stimulation of G proteins is believed
      to occur via insertion of mastoparan into the phospholipid membrane to form a
      highly structured alpha-helix that resembles the intracellular loops of G protein
      coupled adrenergic receptors. Consequently, the presence of adrenoceptors and the
      presence of an endogenous beta-adrenergic agonist at the SV membrane is
      suggested. Immunoblot analysis of SV using beta-adrenergic receptor antibody, and
      vesicle swelling experiments using beta-adrenergic agonists and antagonists,
      demonstrate the presence of functional beta-adrenergic receptors at the SV
      membrane. Since a recent study shows vH(+) -ATPase to be upstream of AQP-6 in the
      pathway leading from G(alphao) -mediated swelling of SV, participation of an
      endogenous beta-adrenergic agonist, in the binding and stimulation of its
      receptor to initiate the swelling cascade is demonstrated.

PMID- 20132411
TI  - Interstitial cells of Cajal, macrophages and mast cells in the gut musculature:
      morphology, distribution, spatial and possible functional interactions.
AB  - Interstitial cells of Cajal (ICC) are recognized as pacemaker cells for
      gastrointestinal movement and are suggested to be mediators of neuromuscular
      transmission. Intestinal motility disturbances are often associated with a
      reduced number of ICC and/or ultrastructural damage, sometimes associated with
      immune cells. Macrophages and mast cells in the intestinal muscularis externa of
      rodents can be found in close spatial contact with ICC. Macrophages are a
      constant and regularly distributed cell population in the serosa and at the level
      of Auerbach's plexus (AP). In human colon, ICC are in close contact with
      macrophages at the level of AP, suggesting functional interaction. It has
      therefore been proposed that ICC and macrophages interact. Macrophages and mast
      cells are considered to play important roles in the innate immune defence by
      producing pro-inflammatory mediators during classical activation, which may in
      itself result in damage to the tissue. They also take part in alternative
      activation which is associated with anti-inflammatory mediators, tissue
      remodelling and homeostasis, cancer, helminth infections and immunophenotype
      switch. ICC become damaged under various circumstances - surgical resection,
      possibly post-operative ileus in rodents - where innate activation takes place,
      and in helminth infections - where alternative activation takes place. During
      alternative activation the muscularis macrophage can switch phenotype resulting
      in up-regulation of F4/80 and the mannose receptor. In more chronic conditions
      such as Crohn's disease and achalasia, ICC and mast cells develop close spatial
      contacts and piecemeal degranulation is possibly triggered.

PMID- 20132412
TI  - Imipramine inhibition of TRPM-like plasmalemmal Mg2+ transport in vascular smooth
      muscle cells.
AB  - Depression is associated with vascular disease, such as myocardial infarction and
      stroke. Pharmacological treatments may contribute to this association. On the
      other hand, Mg(2+) deficiency is also known to be a risk factor for the same
      category of diseases. In the present study, we examined the effect of imipramine
      on Mg(2+) homeostasis in vascular smooth muscle, especially via melastatin-type
      transient receptor potential (TRPM)-like Mg(2+) -permeable channels. The
      intracellular free Mg(2+) concentration ([Mg(2+) ](i) ) was measured using (31) P
      nuclear magnetic resonance (NMR) in porcine carotid arteries that express both
      TRPM6 and TRPM7, the latter being predominant. pH(i) and intracellular phosphorus
      compounds were simultaneously monitored. To rule out Na(+) -dependent Mg(2+)
      transport, and to facilitate the activity of Mg(2+) -permeable channels,
      experiments were carried out in the absence of Na(+) and Ca(2+) . Changing the
      extracellular Mg(2+) concentration to 0 and 6 mM significantly decreased and
      increased [Mg(2+) ](i) , respectively, in a time-dependent manner. Imipramine
      statistically significantly attenuated both of the bi-directional [Mg(2+) ](i)
      changes under the Na(+) - and Ca(2+) -free conditions. This inhibitory effect was
      comparable in influx, and much more potent in efflux to that of 2
      aminoethoxydiphenyl borate, a well-known blocker of TRPM7, a channel that plays a
      major role in cellular Mg(2+) homeostasis. Neither [ATP](i) nor pH(i) correlated
      with changes in [Mg(2+) ](i) . The results indicate that imipramine suppresses
      Mg(2+) -permeable channels presumably through a direct effect on the channel
      domain. This inhibitory effect appears to contribute, at least partially, to the
      link between antidepressants and the risk of vascular diseases.

PMID- 20132413
TI  - Gene expression signatures differentiate ovarian/peritoneal  serous carcinoma
      from breast carcinoma in effusions.
AB  - Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological
      cancers that most frequently involve the serosal cavities.With the objective of
      improving on the limited diagnostic panel currently available for the
      differential diagnosis of these two malignancies,as well as to define tumour
      specific biological targets, we compared their global gene expression patterns.
      Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast
      carcinoma effusions were analysed using the HumanRef-8 BeadChip from
      Illumina.Differentially expressed candidate genes were validated using
      quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical
      clustering using all 54,675 genes in the array separated ovarian from breast
      carcinoma samples. We identified 288 unique probes that were significantly
      differentially expressed in the two cancers by greater than 3.5-fold, of which 81
      and 207 were overexpressed in breast and ovarian/peritoneal carcinoma,
      respectively. SAM analysis identified 1078 differentially expressed probes with
      false discovery rate less than 0.05. Genes overexpressed in breast carcinoma
      included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and
      KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1,
      MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3,PAX8, APOL2 and NRCAM. The differential
      expression of 14 genes was validated by quantitative real-time PCR, and
      differences in 5 gene products were confirmed by immunohistochemistry. Expression
      profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and
      identifies genes that are differentially expressed in these two tumour types. The
      molecular signatures unique to these cancers may facilitate their differential
      diagnosis and may provide a molecular basis for therapeutic target discovery.

PMID- 20132415
TI  - The contribution of Kv7 channels to pregnant mouse and human myometrial
      contractility.
AB  - Premature birth accounts for approximately 75% of neonatal mortality and
      morbidity in the developed world. Despite this, methods for identifying and
      treating women at risk of preterm labour are limited and many women still present
      in preterm labour requiring tocolytic therapy to suppress uterine contractility.
      The aim of this study was to assess the utility of Kv7 channel activators as
      potential uterine smooth muscle (myometrium) relaxants in tissues from pregnant
      mice and women. Myometrium was obtained from early and late pregnant mice and
      from lipopolysaccharide (LPS)-injected mice (day 15 of gestation; model of
      infection in pregnancy). Human myometrium was obtained at the time of Caesarean
      section from women at term (38-41 weeks). RT-PCR/qRT-PCR detected KCNQ and KCNE
      expression in mouse and human myometrium. In mice, there was a global suppression
      of all KCNQ isoforms, except KCNQ3, in early pregnancy (n= 6, P < 0.001 versus
      late pregnant); expression subsequently increased in late pregnancy (n= 6). KCNE
      isoforms were also gestationally regulated (P < 0.05). KCNQ and KCNE isoform
      expression was slightly down-regulated in myometrium from LPS-treated-mice versus
      controls (P < 0.05, n= 3-4). XE991 (10 MUM, Kv7 inhibitor) significantly
      increased spontaneous myometrial contractions in vitro in both human and mouse
      myometrial tissues (P < 0.05) and retigabine/flupirtine (20 MUM, Kv7 channel
      activators) caused profound myometrial relaxation (P < 0.05). In summary, Kv7
      activators suppressed myometrial contraction and KCNQ gene expression was
      sustained throughout gestation, particularly at term. Consequently, activation of
      the encoded channels represents a novel mechanism for treatment of preterm
      labour.

PMID- 20132416
TI  - Combinatorial interference of toll-like receptor 2 and 4 synergistically
      stabilizes atherosclerotic plaque in apolipoprotein E-knockout mice.
AB  - To test the hypothesis that combinatorial interference of toll-like receptor 2
      (TLR2) and TLR4 is superior to isolated interference of TLR2 or TLR4 in
      stabilizing atherosclerotic plaques, lentiviruses carrying small interfering RNA
      of TLR2 or TLR4 were constructed and proved efficacious for knocking down mRNA
      and protein expression of TLR2 or TLR4 significantly in vitro. One hundred and
      fifty apolipoprotein E(-/-) mice fed a high-fat diet were divided into the
      control, mock, TLR2i, TLR4i and TLR2 + 4i subgroups and a constrictive collar was
      placed around carotid artery of these mice to induce plaque formation. TLR2i and
      TLR4i viral suspension was transfected into carotid plaques, respectively, in
      TLR2i and TLR4i subgroups, or in combination in TLR2 + 4i subgroup. Four weeks
      after lentivirus transfection, mRNA and protein expression of TLR2 or TLR4 was
      attenuated markedly in carotid plaques, leading to reduced local inflammatory
      cytokine expression and plaque content of lipid and macrophages, increased plaque
      content of collagen and lowered plaque vulnerability index. Factorial ANOVA
      analysis revealed that there was a synergistic effect between TLR4i and TLR2i in
      stabilizing plaques. In conclusion, combinatorial interference of TLR2 and TLR4
      reduces local inflammation and stabilizes plaques more effectively than
      interference of TLR2 or TLR4 alone.

PMID- 20132414
TI  - Epigenetics in atherosclerosis and inflammation.
AB  - Atherosclerosis is a multifactorial disease with a severe burden on western
      society. Recent insights into the pathogenesis of atherosclerosis underscore the
      importance of chronic inflammation in both the initiation and progression of
      vascular remodelling. Expression of immunoregulatory molecules by vascular wall
      components within the atherosclerotic lesions is accordingly thought to
      contribute to the ongoing inflammatory process. Besides gene regulatory proteins
      (transcription factors), epigenetic mechanisms also play an essential and
      fundamental role in the transcriptional control of gene expression. These
      epigenetic mechanisms change the accessibility of chromatin by DNA methylation
      and histone modifications. Epigenetic modulators are thus critically involved in
      the regulation of vascular, immune and tissue-specific gene expression within the
      atherosclerotic lesion. Importantly, epigenetic processes are reversible and may
      provide an excellent therapeutic target. The concept of epigenetic regulation is
      gradually being recognized as an important factor in the pathogenesis of
      atherosclerosis. Recent research provides an essential link between inflammation
      and reprogramming of the epigenome. In this review we therefore discuss the basis
      of epigenetic regulation - and the contribution thereof in the regulation of
      inflammatory processes in general and during atherosclerosis in particular.
      Moreover we highlight potential therapeutic interventions based on epigenetic
      mechanisms.

PMID- 20132417
TI  - Emotional lability in children and adolescents with attention
      deficit/hyperactivity disorder (ADHD): clinical correlates and familial
      prevalence.
AB  - BACKGROUND: The goal of this study was to investigate the occurrence, severity
      and clinical correlates of emotional lability (EL) in children with attention
      deficit/hyperactivity disorder (ADHD), and to examine factors contributing to EL
      and familiality of EL in youth with ADHD. METHODS: One thousand, one hundred and
      eighty-six children with ADHD combined type and 1827 siblings (aged 6-18 years)
      were assessed for symptoms of EL, ADHD, associated psychopathology and comorbid
      psychiatric disorders with a structured diagnostic interview (PACS) as well as
      parent and teacher ratings of psychopathology (SDQ; CPRS-R:L; CTRS-R:L). Analyses
      of variance, regression analyses, chi(2)-tests or loglinear models were applied.
      RESULTS: Mean age and gender-standardized ratings of EL in children with ADHD
      were >1.5 SD above the mean in normative samples. Severe EL (>75th percentile)
      was associated with more severe ADHD core symptoms, primarily hyperactive
      impulsive symptoms, and more comorbid oppositional defiant, affective and
      substance use disorders. Age, hyperactive-impulsive, oppositional, and emotional
      symptoms accounted for 30% of EL variance; hyperactive-impulsive symptoms did not
      account for EL variance when coexisting oppositional and emotional problems were
      taken into account, but oppositional symptoms explained 12% of EL variance
      specifically. Severity of EL in probands increased the severity of EL in
      siblings, but not the prevalence rates of ADHD or ODD. EL and ADHD does not co
      segregate within families. CONCLUSION: EL is a frequent clinical problem in
      children with ADHD. It is associated with increased severity of ADHD core
      symptoms, particularly hyperactivity-impulsivity, and more symptoms of comorbid
      psychopathology, primarily symptoms of oppositional defiant disorder (ODD), but
      also affective symptoms, and substance abuse. EL in ADHD seems to be more closely
      related to ODD than to ADHD core symptoms, and is only partly explainable by the
      severity of ADHD core symptoms and associated psychopathology. Although EL
      symptoms are transmitted within families, EL in children with ADHD does not
      increase the risk of ADHD and ODD in their siblings.

PMID- 20132418
TI  - Developmental transitions to psychopathology: are there prodromes of substance
      use disorders?

PMID- 20132419
TI  - Families promote emotional and behavioural resilience to bullying: evidence of an
      environmental effect.
AB  - BACKGROUND: Bullied children are at risk for later emotional and behavioural
      problems. 'Resilient' children function better than would be expected given their
      experience of bullying victimisation. This study examined the role of families in
      promoting resilience following bullying victimisation in primary school. METHOD:
      Data were from the Environmental Risk (E-Risk) Study which describes a nationally
      representative sample of 1,116 twin pairs and their families. We used mothers'
      and children's reports to examine bullying victimisation during primary school
      and mothers' and teachers' reports to measure children's emotional and
      behavioural adjustment at ages 10 and 12. We used mothers' and interviewers'
      reports to derive measures of protective factors in the home including maternal
      warmth, sibling warmth and positive atmosphere at home. RESULTS: Results from
      linear regression models showed that family factors were associated with
      children's resilience to bullying victimisation. Maternal warmth, sibling warmth
      and a positive atmosphere at home were particularly important in bullied children
      compared to non-bullied children in promoting emotional and behavioural
      adjustment. We used a twin differences design to separate out environmental
      protective factors in twins who are genetically identical. Differences in
      maternal warmth between twins from genetically identical monozygotic pairs
      concordant for bullying victimisation were correlated with twin differences in
      behavioural problems (r = -.23) such that the twin who received the most warmth
      had fewer behavioural problems. This shows that maternal warmth has an
      environmental effect in protecting children from the negative outcomes associated
      with being bullied. CONCLUSIONS: Warm family relationships and positive home
      environments help to buffer children from the negative outcomes associated with
      bullying victimisation. Warm parent-child relationships can exert an
      environmentally mediated effect on children's behavioural adjustment following
      bullying victimisation. Identifying protective factors that promote resilience to
      bullying victimisation could lead to improved intervention strategies targeting
      the home environment.

PMID- 20132420
TI  - Churg-Strauss syndrome with coexistence of eosinophilic vasculitis, granulomatous
      phlebitis and granulomatous dermatitis in bullous pemphigoid-like blisters.
AB  - The main histopathological features in the cutaneous lesions of Churg-Strauss
      syndrome (CSS) are dermal leukocytoclastic vasculitis with a variable
      eosinophilic infiltrate and non-vasculitic tissue eosinophilia with granuloma
      formation. This wide histopathological spectrum may account for the various skin
      manifestations of CSS. However, the unique histopathological combination of
      dermal eosinophilic vasculitis and subcutaneous granulomatous phlebitis
      accompanied by bulla formation has not been previously described. We report an
      unusual CSS case showing dermal necrotizing eosinophilic vasculitis and
      granulomatous phlebitis in purpuric lesions coupled with subepidermal blistering.
      The blisters showed dermal granulomatous dermatitis and eosinophilia without
      evidence of vasculitis. Dermal necrotizing eosinophilic vasculitis was
      characterized by fibrinoid alteration of the vessel wall, a prominent
      perivascular eosinophilic infiltrate, a few infiltrating histiocytes along the
      affected vessel wall, and the absence of neutrophilic infiltration. The
      underlying subcutaneous granulomatous phlebitis was characterized by an
      angiocentric histiocytic infiltrate surrounded by marked eosinophilic infiltrate.
      Deposition of cytotoxic proteins and radicals derived from eosinophils in the
      vessel walls and papillary dermis followed by a secondary granulomatous response
      may account for the unique clinical and histopathological features in this case.

PMID- 20132421
TI  - Non-mycosis fungoides cutaneous T-cell lymphoma: reclassification according to
      the WHO-EORTC classification.
AB  - BACKGROUND: Non-mycosis fungoides (non-MF) primary cutaneous T-cell lymphomas
      (PCTCL) are heterogeneous and divided into subgroups by the World Health
      Organization-European Organization for Research and Treatment of Cancer (WHO
      EORTC) classification of cutaneous lymphomas. We report the first North American
      series to examine the applicability of the classification, compare our findings
      with the predominant European literature and confirm the significance of
      separation into the indolent and aggressive groups. METHODS: Forty-four non-MF
      PCTCL cases with available tissue for phenotyping, adequate clinical staging
      information and follow-up were reclassified according to the WHO-EORTC
      classification. RESULTS: Non-MF PCTCL had a longer overall survival (OS) (13.8
      years) compared with secondary cutaneous T-cell lymphoma (SC-TCL) (2.5 years).
      Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) had the most favorable
      outcome (OS 14.1 years), whereas secondary and primary peripheral T-cell
      lymphoma, unspecified had the shortest OS (2.5 and 2.4 years, respectively).
      Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (CTLCD4)
      appeared to have a favorable course. CONCLUSIONS: Most non-MF PCTCL can be
      classified according to the WHO-EORTC classification. The relative frequencies
      are similar to European experience. Non-MF PCTCL is a heterogeneous group with a
      favorable outcome compared to SC-TCL, especially PC-ALCL and CTLCD4. Separation
      of non-MF PCTCL into indolent and aggressive groups appears clinically
      significant and may provide direction for therapeutic decisions.

PMID- 20132422
TI  - Brooke-Spiegler syndrome: report of a case with a novel mutation in the CYLD gene
      and different types of somatic mutations in benign and malignant tumors.
AB  - The authors report a case of Brooke-Spiegler syndrome (BSS) with a novel germline
      CYLD mutation and various somatic mutations identified in the lesional tissues.
      The patient was a 46-year-old man with multiple lesions on the face. The
      available histopathological material included 24 trichoepitheliomas, 2 large
      nodular basal cell carcinomas (BCCs), 2 spiradenomas, 1 spiradenocylindroma and 1
      trichoblastoma composed of large and small nodules with prominent clear cell
      differentiation. Whereas one of the two BCCs manifested a conventional
      morphology, the second neoplasm additionally showed foci with high grade
      cytological features characterized by marked pleomorphism and numerous mitotic
      figures. There were also numerous signet ring cells and cells containing
      intracytoplasmic eosinophilic inclusions. The germline mutation was a
      substitution mutation c.1684 + 1G> A. Somatic mutations were investigated in
      eight tissue blocks from which high quality genomic DNA had been successfully
      extracted. Somatic mutations included loss of heterozygosity (LOH) in four
      lesions and a single sequence mutation, namely a single base deletion c. 2322delA
      causing a frameshift mutation E774DfsX2. LOH occurred in both BCCs, one
      trichoepithelioma and one spiradenoma. In the remaining three lesions, the
      somatic event remained undetected.

PMID- 20132423
TI  - 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms.
AB  - The terms 'epidermotropism' and 'exocytosis' are commonly used to describe
      intraepithelial lymphocytes in the mycosis fungoides (MF) variant of cutaneous T
      cell lymphoma (CTCL). However, both terms have not been uniformly or consistently
      defined. In this study, definitions of both terms were requested from 34 experts.
      In definitions provided by 19 responders, 'epidermotropism' correlated with
      MF/CTCL, and 'exocytosis' correlated with benign conditions. Use of these terms
      often reflected the observer's interpretation, as they were not always used in
      purely descriptive fashion.

PMID- 20132425
TI  - Role of Helicobacter pylori infection in gastric cancer pathogenesis: a chance
      for prevention.
AB  - Gastric cancer in the absence of strategies implemented for early detection
      continues to have a dismal prognosis. There are limited options for a curative
      therapy once patients present with clinical manifestations of this malignant
      disease. Helicobacter pylori (H. pylori) infection plays a key role in gastric
      carcinogenesis, supported by epidemiological, preclinical and clinical studies.
      The recognition of H. pylori infection as a critical risk factor in the
      development of gastric cancer opens the chance for new venues in prevention
      strategies.

PMID- 20132426
TI  - Endoscopic closure of acute iatrogenic perforations during diagnostic and
      therapeutic endoscopy in the gastrointestinal tract using metallic clips: a
      literature review.
AB  - Iatrogenic perforations that occur during the endoscopic procedures are generally
      surgically managed, even if some authors prefer a non-surgical approach in
      selected cases. The endoscopic application of metallic clips has been widely used
      in the gastrointestinal (GI) tract for hemostasis and also for marking lesions.
      Since 1993 several series of endoscopic perforations treated with endoclips have
      been described in the literature. In this review we offer a descriptive analysis
      of the reported cases of the acute iatrogenic perforation, describing the closure
      of different perforations occurring in the GI tract, treated with metallic clips.

PMID- 20132427
TI  - To Bravo or not? A comparison of wireless esophageal pH monitoring and
      conventional pH catheter to evaluate non-erosive gastroesophageal reflux disease
      in a multiracial Asian cohort.
AB  - OBJECTIVE: Non-erosive reflux disease (NERD) constitutes the majority of patients
      with gastroesophageal reflux disease (GERD). Esophageal pH monitoring is useful
      in distinguishing patients with NERD from functional heartburn. The
      gastroenterologist often faces the dilemma of choosing the most appropriate
      investigative modality. The wireless Bravo capsule allows prolonged 48 hour
      monitoring with improved patient tolerance, but concerns regarding its reduced
      sensitivity compared to conventional pH catheter have been raised. We compared
      the prevalence of high esophageal acid exposure and positive symptom correlation
      profiles (using the symptom index [SI] and symptom association probability [SAP])
      in patients who underwent Bravo compared to patients who underwent conventional
      pH catheter, and evaluated the efficacy of Bravo monitoring in a multiracial
      Asian cohort. METHODS: Retrospective analysis of all pH studies performed between
      January 2004 and February 2009 for patients with persistent reflux symptoms and a
      normal gastroscopy. RESULTS: 66 (27 Male, 42.4 +/- 13.4 years) and 55 (24 Male,
      47.1 +/- 13.3 years) patients underwent wireless and pH catheter evaluation
      respectively. "True NERD" (abnormal acid exposure) was diagnosed in 26 (39.4%)
      and 20 (36.4%) patients (pNS) while "acid-sensitive esophagus" (SI > or = 50%
      and/or SAP > or = 95%) occurred in 14 (21.2%) and 12 (21.8%) patients (pNS) using
      the wireless and pH catheter respectively. Extended recording time with Bravo led
      to an incremental diagnostic yield of 30%. CONCLUSION: The wireless capsule was
      well tolerated. The diagnostic yield was similar using both modalities. With the
      increasing availability of impedance-pH technology, it is uncertain if devices
      that detect only acid-reflux events will be surpassed.

PMID- 20132428
TI  - Late presentation of esophageal cancer: observations in a multiracial South-East
      Asian population.
AB  - OBJECTIVE: Esophageal cancer (ECA) is an important cancer in Malaysia. The aim of
      the study is to review the demographic data and clinical presentation of patients
      with ECA seen at the University of Malaya Medical Centre, Kuala Lumpur. METHODS:
      Patients with histologically proven ECA were recruited for the study. Patients'
      case notes, endoscopy and operating theater records were reviewed. All cases were
      histologically confirmed. RESULTS: A total of 143 patients with ECA was diagnosed
      between 1998 and 2003. The mean age of the patients was 63.1 +/- 12.1 years with
      a male : female ratio of 1.8:1. Of these 50.3 percent were Indians, 32.9 percent,
      Chinese and 16.8 percent Malays. The overall hospital-based prevalence rates per
      100 000 admissions according to races were: Malay; 23.5, Chinese; 57.4 and
      Indian; 134.1. The location of the tumors was: upper; 16 (11.2%) middle; 52
      (36.4%) and lower; 75 (52.4%). The histological type of ECA were: squamous cell
      carcinomas; 113 (79.0%) and adenocarcinomas; 30 (21.0%). The ECA stage at
      diagnosis, was: II; 18 (12.6%), III; 23 (16.1%) and IV; 102 (71.3%). Only 24
      (16.8%) patients underwent surgery and13 (9.1%) were considered curative. Overall
      114 (79.7%) patients underwent palliative endoscopic stenting and six (4.2%) were
      given other palliative therapy including radiotherapy. CONCLUSIONS: Squamous cell
      cancer was the predominant type. ECA presents late in our patients and only a
      minority of patients underwent curative surgery.

PMID- 20132429
TI  - Rofecoxib augments anticancer effects by reversing intrinsic multidrug resistance
      gene expression in BGC-823 gastric cancer cells.
AB  - OBJECTIVE: To investigate combined chemotherapeutic effects of rofecoxib in
      combination with 5-fluorouracil (5-FU), cisplatin (DDP) and etoposide (VP-16) in
      vitro, and to explore the potential mechanisms in modulating multidrug resistance
      (MDR) expression. METHODS: The BGC-823 gastric cancer cell line was incubated for
      48 h with 0.1 micromol/L rofecoxib, 5-FU, DDP and VP-16 (1 microg/mL, 10
      microg/mL and 100 microg/mL) alone, and combined with rofecoxib, respectively.
      Methyl-thiazolyl-tetrazolium and the terminal deoxynucleotidyl transferase
      mediated 2'-deoxyuridine 5'-yriphosphate nick-end labeling assays were performed
      to calculate inhibitory rates and apoptotic index. Middle effects principles (CI
      values) were used to determine the interaction between rofecoxib and
      chemotherapeutic agents. Reverse transcription-polymerase chain reaction (RT-PCR)
      and Western blot analysis were employed to determine expression of MDR1,
      multidrug resistance-associated protein 1 (MRP1), glutathione S-tranferase-pi
      (GST-pi) mRNA and protein in gastric cancer cells administered by rofecoxib,
      respectively. RESULTS: Both anticancer drugs such as 5-FU, DDP and VP-16 and
      rofecoxib inhibited the cells' proliferation and induced apoptosis in a dose
      dependent manner, and a more significant inhibition was achieved when the cells
      were co-treated with anticancer drugs and rofecoxib. There was a synergetic role
      when different concentrations of chemotherapeutic agents were combined with
      rofecoxib (all CI < 1, P < 0.01 or 0.05). RT-PCR analyses of MDR gene families in
      BGC-823 gastric cancer cells revealed a strong expression in MRP1 and GST-pi
      mRNA, but MDR1 mRNA was undetectable. After administration with different
      concentrations of rofecoxib (0.1, 1.0, 10 micromol/L), significant downregulation
      of MRP1 and GST-pi mRNA was observed (MRP1: from 0.984 +/- 0.093-0.513 +/- 0.098;
      GST-pi: from 1.078 +/- 0.201-0.472 +/- 0.084, P < 0.01 or 0.05). In addition,
      MRP1 and GST-pi protein expression induced by rofecoxib were also reduced (P <
      0.01 or 0.05). CONCLUSION: Rofecoxib, a specific cyclooxygenase-2 inhibitor,
      plays a chemotherapeutic sensitizer role in various anticancer agents on the BGC
      823 gastric cancer cell line, which could be partly explained by its ability to
      reverse the intrinsic MRP1 and GST-piin vitro.

PMID- 20132430
TI  - Involvement of VDAC1 and Bcl-2 family of proteins in VacA-induced cytochrome c
      release and apoptosis of gastric epithelial carcinoma cells.
AB  - OBJECTIVE: It is known that the vacuolating cytotoxin (VacA) could induce
      apoptosis. However, the mechanism remained to be elucidated. The aim of this
      study is to investigate the role of Bcl family of proteins (Bcl-2 and Bax) and
      the mitochondrial voltage-dependent anion channel (VDAC) in VacA-induced
      apoptosis of AGS cells. METHODS: Plasmid pGBKT7-VacA p58 was constructed and
      transfected into the AGS cells. RT-PCR and Western blotting were used to
      determine the expressions of cytochrome c, caspase-3, Bax, Bcl-2 and VDAC1 mRNA
      and proteins. RESULTS: VacA p58 can induce cytochrome c release and activate
      caspase-3 in AGS cells. It up-regulated the expressions of Bax and VDAC1 mRNA and
      proteins, and decreased the expression of Bcl-2 in AGS cells. CONCLUSION: VacA
      p58 induces apoptosis in AGS cells. This apoptotic process is associated with the
      up-regulation of Bax/VDAC1 and downregulation of Bcl-2. These findings suggest
      that the release of cytochrome c by VacA p58 is mainly through VDAC-dependent and
      Bcl-2 family-dependent pathways.

PMID- 20132431
TI  - Initial study of microRNA expression profiles of colonic cancer without lymph
      node metastasis.
AB  - OBJECTIVE: To investigate the difference of microRNA expression profiles between
      colonic cancer without lymph node metastasis and the para-cancerous control, to
      identify the specific microRNA associated with the cancer and to predict the
      carcinogenetic mechanism of microRNA on the basis of these results. METHODS: The
      microRNA (miRNA) were extracted and isolated from six specimens, including
      colonic cancerous and para-cancerous ones, all of which were confirmed to be
      without lymph node metastasis. Agilent microRNA microarrays consisting of 723
      probes were used for screening the expression differences of microRNA. Data were
      analyzed using feature extraction software. The expression level of
      differentially expressed microRNA using quantitative real-time polymerase chain
      reaction (RT-PCR) was validated. RESULTS: A total of 14 miRNAs were found to be
      associated with colonic cancer, in which the expression of miR-106b, miR-135b,
      miR-18a, miR-18b, miR-196b, miR-19a, miR-224, miR-335, miR-424, miR-20a*, miR
      301b and miR-374a were up-regulated and the expression of miR-378 and miR-378*
      were downregulated in colonic cancer tissues, compared with the para-cancerous
      control. The expression level of miR-18a and miR-135b were validated in
      accordance with the results of RT-PCR. CONCLUSION: The miRNAs are differentially
      expressed between colonic tumor tissues and para-cancerous tissues. Many of these
      miRNAs are expected to participate in the process of multiple tumorigenesis.
      These miRNAs could play an important role in the carcinogenesis of colon. These
      results provide new insights in human colorectal cancer genesis.

PMID- 20132432
TI  - SIRT3 reduces lipid accumulation via AMPK activation in human hepatic cells.
AB  - OBJECTIVE: Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD)(+)
      dependent protein deacetylase localized on mitochondria and regulates the
      adaptive thermogenesis in brown adipocytes. This study aims to investigate the
      role of SIRT3 in hepatic lipid accumulation, and whether the activation of
      adenosine monophosphate (AMP)-activated protein kinase (AMPK) is required.
      METHODS: A retroviral system was used for overexpressing of SIRT3 in HepG2 cells,
      whereas a lentivirus-mediated vector encoding SIRT3 small interfering RNA (siRNA)
      was used to infect these cells for knocking down endogenous SIRT3 expression. The
      cells were treated with oleate to induce lipid accumulation and Nile red staining
      was used to assess the number of lipid droplets in HepG2 cells. The AMPK
      signaling pathway was facilitated with the administrating of isoproterenol and an
      immunoblot analysis was performed to assess the phosphorylation of AMPK and
      acetyl coenzyme A carboxylase (ACC). Compound C was adopted to inhibit AMPK
      activity. RESULTS: The number of lipid droplets in HepG2 cells overexpressing
      SIRT3 was significantly lower than that in the control cells (P < 0.05). SIRT3
      infected cells exhibited significantly more phosphorylation of AMPK and ACC (P <
      0.05), which was reversed by the treatment of compound C, an inhibitor of AMPK.
      Knocking down SIRT3 downregulated phosphorylation of AMPK and ACC by 60-80% (P <
      0.05) and promoted lipid accumulation. The activation of AMPK by SIRT3 was
      dependent on SIRT3 deacetylase activity. CONCLUSION: SIRT3 reduces lipid
      accumulation via AMPK activation in human hepatic cells.

PMID- 20132433
TI  - Primary clear cell carcinoma of hilar bile duct: a case report.

PMID- 20132434
TI  - Inhibition of Brochothrix thermosphacta and sensory improvement of tropical
      peeled cooked shrimp by Lactococcus piscium CNCM I-4031.
AB  - AIMS: To investigate the antimicrobial spectrum of Lactococcus piscium CNCM I
      4031 and its protective effect in cooked and peeled shrimp against Brochothrix
      thermosphacta. METHODS AND RESULTS: Sixteen pathogenic and spoiling bacteria were
      inhibited in Elliker, but not in shrimp juice agar plates. In shrimp packed under
      modified atmosphere and stored at 8 degrees C, B. thermosphacta (10(3) CFU g(-1))
      was inhibited by 4.1 log CFU g(-1) when co-inoculated with L. piscium (10(6) CFU
      g(-1)). Brochothrix thermosphacta spoiled the product after 11 days, with the
      emission of strong butter/caramel off-odours. In co-culture with L. piscium,
      sensory shelf-life was extended by at least 10 days. The inhibition was partially
      explained by a drop in pH from 6.6 to 5.6. The physicochemical composition of
      shrimp and shrimp juice was established to identify the inhibition mechanisms
      involved. CONCLUSION: Lactococcus piscium CNCM I-4031 has a wide antimicrobial
      spectrum. The strain inhibits B. thermosphacta in shrimp and significantly
      prolongs sensory shelf-life. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactococcus
      piscium CNCM I-4031 is shown to be a promising agent for improving shrimp quality
      and may be tested against pathogens and in other food matrices. Knowledge of the
      physicochemical composition of shrimp and shrimp juice will allow the development
      of a chemically defined model medium for determining the inhibition mechanisms
      involved.

PMID- 20132435
TI  - Antibacterial activity of silver nanoparticles (AgNps) synthesized by tea leaf
      extracts against pathogenic Vibrio harveyi and its protective efficacy on
      juvenile Feneropenaeus indicus.
AB  - AIMS: To determine the antibacterial potential of silver nanoparticles (AgNps)
      synthesized by tea leaf extract against Vibrio harveyi and its protective effect
      on juvenile Feneropenaeus indicus. METHODS AND RESULTS: AgNps were synthesized by
      a simple procedure using tea leaf extract as the reducing agent. Bacteriological
      tests were performed in Luria-Bertani medium on solid agar plates and in liquid
      systems supplemented with V. harveyi against different concentrations of AgNps.
      AgNps synthesized in the present study were shown to be effective against V.
      harveyi isolated from F. indicus. The combined results of long- and short-term
      treatment of AgNps synthesized by tea leaf extract showed a 71% reduction in
      accumulated mortality. CONCLUSIONS: The long-term administration of AgNps
      synthesized by tea leaf extracts at the concentration of 10 microg significantly
      reduced the mortalities in F. indicus from V. harveyi infections. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The AgNps synthesized by tea leaf extract may be an
      alternative to antibiotics in controlling V. harveyi infections.

PMID- 20132436
TI  - Flow cytometric method for quantifying viable Mycoplasma agassizii, an agent of
      upper respiratory tract disease in the desert tortoise (Gopherus agassizii).
AB  - AIMS: Mycoplasma agassizii can cause upper respiratory tract disease in the
      threatened desert tortoise of the Southwestern United States. Two technical
      challenges have impeded critical microbiological studies of this microorganism:
      (i) its small size limits the use of light microscopy for cell counting and (ii)
      its extremely slow growth in broth and agar cultures impedes colony counting. Our
      aim was to develop a rapid and sensitive flow cytometric method using a vital
      fluorescent dye to enumerate viable M. agassizii cells. METHODS AND RESULTS:
      Here, we demonstrate that the nonfluorescent molecule 5-carboxyfluorescein (5-CF)
      diacetate acetoxymethyl ester penetrates M. agassizii cell membranes and it is
      converted in the cytoplasm to the fluorescent molecule 5-CF by the action of
      intracellular esterases. Labelled mycoplasma cells can be easily detected by flow
      cytometry, and cultures with as few as 100 viable mycoplasma cells ml(-1) can be
      labelled and counted in less than 1 h. Experiments using temperature-induced cell
      death demonstrated that only viable M. agassizii cells are labelled with this
      procedure. CONCLUSIONS: A rapid and sensitive flow cytometric technique has been
      developed for enumerating viable M. agassizii cells. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This technique should facilitate basic immunological, biochemical and
      pharmacological studies of this important pathogen which may lead to new
      diagnostic and therapeutic methods.

PMID- 20132437
TI  - Functional regions of the N-terminal domain of the antiterminator RfaH.
AB  - RfaH is a bacterial elongation factor that increases expression of distal genes
      in several long, horizontally acquired operons. RfaH is recruited to the
      transcription complex during RNA chain elongation through specific interactions
      with a DNA element called ops. Following recruitment, RfaH remains bound to RNA
      polymerase (RNAP) and acts as an antiterminator by reducing RNAP pausing and
      termination at some factor-independent and Rho-dependent signals. RfaH consists
      of two domains connected by a flexible linker. The N-terminal RfaH domain
      (RfaH(N)) recognizes the ops element, binds to the RNAP and reduces pausing and
      termination in vitro. Functional analysis of single substitutions in this domain
      reported here suggests that three separate RfaH(N) regions mediate these
      functions. We propose that a polar patch on one side of RfaH(N) interacts with
      the non-template DNA strand during recruitment, whereas a hydrophobic surface on
      the opposite side of RfaH(N) remains bound to the beta' subunit clamp helices
      domain throughout transcription of the entire operon. The third region is
      apparently dispensable for RfaH binding to the transcription complex but is
      required for the antitermination modification of RNAP.

PMID- 20132438
TI  - Examination of the interaction between FtsZ and MinCN in E. coli suggests how
      MinC disrupts Z rings.
AB  - In Escherichia coli the Min system prevents Z ring assembly at cell poles by
      topologically regulating the division inhibitor MinC. The MinC protein has two
      domains of equal size and both domains can target FtsZ and block cell division in
      the proper context. Recently, we have shown that, along with MinD, the C-terminal
      domain of MinC (MinC(C)) competes with FtsA, and to a lesser extent with ZipA,
      for interaction with the C-terminal tail of FtsZ to block division. Here we
      explored the interaction between the N-terminal domain of MinC (MinC(N)) and
      FtsZ. A search for mutations in ftsZ that confer resistance to MinC(N) identified
      an alpha-helix at the interface of FtsZ subunits as being critical for the
      activity of MinC(N). Focusing on one such mutant FtsZ-N280D, we showed that it
      greatly reduced the FtsZ-MinC interaction and was resistant to MinC(N) both in
      vivo and in vitro. With these results, an updated model for the action of MinC on
      FtsZ is proposed: MinC interacts with FtsZ to disrupt two interactions, FtsZ
      FtsA/ZipA and FtsZ-FtsZ, both of which are essential for Z ring formation.

PMID- 20132439
TI  - Phosphorylation of phosducin-like protein BDM-1 by protein kinase 2 (CK2) is
      required for virulence and G beta subunit stability in the fungal plant pathogen
      Cryphonectria parasitica.
AB  - Phosducin-like proteins are conserved regulatory components of G-protein
      signalling pathways, which mediate many physiological processes. Identified
      throughout eukaryotic genomes, they are thought to serve as regulators of G
      betagamma assembly. Cryphonectria parasitica, a plant pathogen and causative
      agent of chestnut blight, contains three G alpha, one G beta, one G gamma
      subunits and phosducin-like protein BDM-1 that have important roles in
      pigmentation, sporulation and virulence. Deletion of either G beta subunit or BDM
      1 produces identical phenotypes. Additionally, we report that the G beta subunit
      is not detectable in absence of BDM-1. Given that the regulatory role of
      phosducin-like proteins may be influenced by protein kinase 2 (CK2), we confirmed
      that BDM-1 is a phosphoprotein that can be targeted by CK2 in vitro. Mutagenesis
      of the five putative CK2 sites revealed that native phosphorylation likely occurs
      at two locations. Strains bearing a single or double serine to alanine
      substitutions at those sites were significantly less virulent with only minor
      phenotypic changes from vegetative colonies. Therefore, CK2 activity appears to
      mediate key signals that are required for virulence, but not for vegetative
      growth. Expression of selected CK2 mutants resulted in reduced accumulation of
      the G beta subunit, suggesting that phosphorylation of BDM-1 influences G beta
      stability.

PMID- 20132440
TI  - Heterochromatic marks are associated with the repression of secondary metabolism
      clusters in Aspergillus nidulans.
AB  - Fungal secondary metabolites are important bioactive compounds but the conditions
      leading to expression of most of the putative secondary metabolism (SM) genes
      predicted by fungal genomics are unknown. Here we describe a novel mechanism
      involved in SM-gene regulation based on the finding that, in Aspergillus
      nidulans, mutants lacking components involved in heterochromatin formation show
      de-repression of genes involved in biosynthesis of sterigmatocystin (ST),
      penicillin and terrequinone A. During the active growth phase, the silent ST gene
      cluster is marked by histone H3 lysine 9 trimethylation and contains high levels
      of the heterochromatin protein-1 (HepA). Upon growth arrest and activation of SM,
      HepA and trimethylated H3K9 levels decrease concomitantly with increasing levels
      of acetylated histone H3. SM-specific chromatin modifications are restricted to
      genes located inside the ST cluster, and constitutive heterochromatic marks
      persist at loci immediately outside the cluster. LaeA, a global activator of SM
      clusters in fungi, counteracts the establishment of heterochromatic marks. Thus,
      one level of regulation of the A. nidulans ST cluster employs epigenetic control
      by H3K9 methylation and HepA binding to establish a repressive chromatin
      structure and LaeA is involved in reversal of this heterochromatic signature
      inside the cluster, but not in that of flanking genes.

PMID- 20132441
TI  - Mutational analysis of the S21 pinholin.
AB  - Lambdoid phage 21 has the prototype pinholin-SAR endolysin lysis system, which is
      widely distributed among phages. Its prototype pinholin, S(21)68, triggers at an
      allele-specific time to form small, heptameric lesions, or pinholes, in the
      cytoplasmic membrane, thus initiating lysis. S(21)68 has two transmembrane
      domains, TMD1 and TMD2. Only TMD2 is required for the formation of pinholes,
      whereas TMD1 acts as an inhibitor of TMD2 and must be externalized to the
      periplasm in the lytic pathway. Previously we provided evidence that S(21)68
      first accumulates as inactive dimers with both transmembrane domains embedded in
      the bilayer. Here we analyse an extensive collection of S(21) mutants to identify
      residues and domains critical to the function and regulation of the pinholin.
      Evidence is presented indicating that, within the inactive dimer, TMD1 acts in
      trans as an inhibitor of the lethal function of TMD2. A wide range of phenotypes,
      from absolute lysis defectives to accelerated lysis triggering, are observed for
      mutations mapping to each topological domain. The pattern of phenotypes allows
      the generation of a model for the structure of the inactive dimer. The model
      identifies the faces of the two transmembrane domains involved in intramolecular
      and intermolecular interactions, as well as interaction with the lipid.

PMID- 20132442
TI  - Novel essential residues of Hda for interaction with DnaA in the regulatory
      inactivation of DnaA: unique roles for Hda AAA Box VI and VII motifs.
AB  - Escherichia coli ATP-DnaA initiates chromosomal replication. For preventing extra
      initiations, a complex of ADP-Hda and the DNA-loaded replicase clamp promotes
      DnaA-ATP hydrolysis, yielding inactive ADP-DnaA. However, the Hda-DnaA
      interaction mode remains unclear except that the Hda Box VII Arg finger (Arg-153)
      and DnaA sensor II Arg-334 within each AAA(+) domain are crucial for the DnaA-ATP
      hydrolysis. Here, we demonstrate that direct and functional interaction of ADP
      Hda with DnaA requires the Hda residues Ser-152, Phe-118 and Asn-122 as well as
      Hda Arg-153 and DnaA Arg-334. Structural analyses suggest intermolecular
      interactions between Hda Ser-152 and DnaA Arg-334 and between Hda Phe-118 and the
      DnaA Walker B motif region, in addition to an intramolecular interaction between
      Hda Asn-122 and Arg-153. These interactions likely sustain a specific association
      of ADP-Hda and DnaA, promoting DnaA-ATP hydrolysis. Consistently, ATP-DnaA and
      ADP-DnaA interact with the ADP-Hda-DNA-clamp complex with similar affinities. Hda
      Phe-118 and Asn-122 are contained in the Box VI region, and their hydrophobic and
      electrostatic features are basically conserved in the corresponding residues of
      other AAA(+) proteins, suggesting a conserved role for Box VI. These findings
      indicate novel interaction mechanisms for Hda-DnaA as well as a potentially
      fundamental mechanism in AAA(+) protein interactions.

PMID- 20132443
TI  - Identification and characterization of E. coli CRISPR-cas promoters and their
      silencing by H-NS.
AB  - Inheritable bacterial defence systems against phage infection and foreign DNA,
      termed CRISPR (clustered regularly interspaced short palindromic repeats),
      consist of cas protein genes and repeat arrays interspaced with sequences
      originating from invaders. The Cas proteins together with processed small spacer
      repeat transcripts (crRNAs) cause degradation of penetrated foreign DNA by
      unknown mechanisms. Here, we have characterized previously unidentified promoters
      of the Escherichia coli CRISPR arrays and cas protein genes. Transcription of
      precursor crRNA is directed by a promoter located within the CRISPR leader. A
      second promoter, directing cas gene transcription, is located upstream of the
      genes encoding proteins of the Cascade complex. Furthermore, we demonstrate that
      the DNA-binding protein H-NS is involved in silencing the CRISPR-cas promoters,
      resulting in cryptic Cas protein expression. Our results demonstrate an active
      involvement of H-NS in the induction of the CRISPR-cas system and suggest a
      potential link between two prokaryotic defence systems against foreign DNA.

PMID- 20132444
TI  - Thymineless death is associated with loss of essential genetic information from
      the replication origin.
AB  - Thymine starvation results in a terminal cellular condition known as thymineless
      death (TLD), which is the basis of action for several common antibiotics and
      anticancer drugs. We characterized the onset and progression of TLD in
      Escherichia coli and found that DNA damage is the only salient property that
      distinguishes cells irreversibly senesced under thymine starvation from cells
      reversibly arrested by the nucleotide limitation. The damage is manifested as the
      relative loss of genetic material spreading outward from the replication origin:
      the extent of TLD correlates with the progression of damage. The reduced
      lethality in mutants deficient in the RecFOR/JQ repair pathway also correlates
      with the extent of damage, which explains most of the observed variance in cell
      killing. We propose that such spatially localized and persistent DNA damage is
      the consequence of transcription-dependent initiation of replication in the
      thymine-starved cells and may be the underlying cause of TLD.

PMID- 20132445
TI  - AcrA suppressor alterations reverse the drug hypersensitivity phenotype of a TolC
      mutant by inducing TolC aperture opening.
AB  - In Escherichia coli, the TolC-AcrAB complex forms a major antibiotic efflux
      system with broad substrate specificity. During the complex assembly, the
      periplasmic helices and bottom turns of TolC are thought to interact with a
      hairpin helix of AcrA and hairpin loops of AcrB respectively. In the present
      study we show that a four-residue substitution in TolC's turn 1, which connects
      outer helices 3 and 4 proximal to TolC's periplasmic aperture, confers antibiotic
      hypersensitivity, without affecting TolC-mediated phage or colicin infection.
      However, despite the null-like drug sensitivity phenotype, chemical cross-linking
      analysis revealed no apparent defects in the ability of the mutant TolC protein
      to physically interact with AcrA and AcrB. A role for TolC turn 1 residues in the
      functional assembly of the tripartite efflux pump complex was uncovered through
      isolating suppressor mutations of the mutant TolC protein that mapped within acrA
      and by utilizing a labile AcrA protein. The data showed that AcrA-mediated
      suppression of antibiotic sensitivity was achieved by dilating the TolC
      aperture/channel in an AcrB-dependent manner. The results underscore the
      importance of the periplasmic turn 1 of TolC in the functional assembly of the
      tripartite efflux complex and AcrA in transitioning TolC from its closed to open
      state.

PMID- 20132446
TI  - A bacterial elongation factor G homologue exclusively functions in ribosome
      recycling in the spirochaete Borrelia burgdorferi.
AB  - Translation elongation factor G (EF-G) in bacteria plays two distinct roles in
      different phases of the translation system. EF-G catalyses the translocation of
      tRNAs on the ribosome in the elongation step, as well as the dissociation of the
      post-termination state ribosome into two subunits in the recycling step. In
      contrast to this conventional view, it has very recently been demonstrated that
      the dual functions of bacterial EF-G are distributed over two different EF-G
      paralogues in human mitochondria. In the present study, we show that the same
      division of roles of EF-G is also found in bacteria. Two EF-G paralogues are
      found in the spirochaete Borrelia burgdorferi, EF-G1 and EF-G2. We demonstrate
      that EF-G1 is a translocase, while EF-G2 is an exclusive recycling factor. We
      further demonstrate that B. burgdorferi EF-G2 does not require GTP hydrolysis for
      ribosome disassembly, provided that translation initiation factor 3 (IF-3) is
      present in the reaction. These results indicate that two B. burgdorferi EF-G
      paralogues are close relatives to mitochondrial EF-G paralogues rather than the
      conventional bacterial EF-G, in both their phylogenetic and biochemical features.

PMID- 20132447
TI  - The concerted action of bZip and cMyb transcription factors FlbB and FlbD induces
      brlA expression and asexual development in Aspergillus nidulans.
AB  - Fungi are capable of generating diverse cell types through developmental
      processes that stem from hyphae, acting as pluripotent cells. The formation of
      mitospores on emergence of hyphae to the air involves the participation of
      transcription factors, which co-ordinate the genesis of new cell types,
      eventually leading to spore formation. In this investigation, we show that bZip
      transcription factor FlbB, which has been attributed to participate in
      transducing the aerial stimulus signal, activates the expression of c-Myb
      transcription factor FlbD. Both factors then jointly activate brlA, a C(2)H(2)
      zinc finger transcription factor, which plays a central role in spore formation.
      This sequence of regulatory events resembles developmental control mechanisms
      involving c-Myb and bZip counterparts in metazoans and plants.

PMID- 20132448
TI  - Epigenetic mechanisms regulate stage differentiation in the minimized protozoan
      Giardia lamblia.
AB  - Histone modification is an important mechanism regulating both gene expression
      and the establishment and maintenance of cellular phenotypes during development.
      Regulation of histone acetylation via histone acetylases and deacetylases (HDACs)
      appears to be particularly crucial in determining gene expression patterns. In
      this study we explored the effect of HDAC inhibition on the life cycle of the
      human pathogen Giardia lamblia, a highly reduced parasitic protozoan
      characterized by minimized cellular processes. We found that the HDAC inhibitor
      FR235222 increased the level of histone acetylation and induced transcriptional
      regulation of approximately 2% of genes in proliferating and encysting parasites.
      In addition, our analyses showed that the levels of histone acetylation decreased
      during differentiation into cysts, the infective stage of the parasite.
      Importantly, FR235222 treatment during encystation reversed this histone hypo
      acetylation and potently blocked the formation of cysts. These results provide
      the first direct evidence for epigenetic regulation of gene expression in this
      simple eukaryote. This suggests that regulation of histone acetylation is
      involved in the control of Giardia stage differentiation, and identifies
      epigenetic mechanisms as a promising target to prevent Giardia transmission.

PMID- 20132449
TI  - Mitochondrial DNA polymerase POLIB is essential for minicircle DNA replication in
      African trypanosomes.
AB  - The unique mitochondrial DNA of trypanosomes is a catenated network of
      minicircles and maxicircles called kinetoplast DNA (kDNA). The network is
      essential for survival, and requires an elaborate topoisomerase-mediated release
      and reattachment mechanism for minicircle theta structure replication. At least
      seven DNA polymerases (pols) are involved in kDNA transactions, including three
      essential proteins related to bacterial DNA pol I (POLIB, POLIC and POLID). How
      Trypanosoma brucei utilizes multiple DNA pols to complete the topologically
      complex task of kDNA replication is unknown. To fill this gap in knowledge we
      investigated the cellular role of POLIB using RNA interference (RNAi). POLIB
      silencing resulted in growth inhibition and progressive loss of kDNA networks.
      Additionally, unreplicated covalently closed precursors become the most abundant
      minicircle replication intermediate as minicircle copy number declines. Leading
      and lagging strand minicircle progeny similarly declined during POLIB silencing,
      indicating POLIB had no apparent strand preference. Interestingly, POLIB RNAi led
      to the accumulation of a novel population of free minicircles that is composed
      mainly of covalently closed minicircle dimers. Based on these data, we propose
      that POLIB performs an essential role at the core of the minicircle replication
      machinery.

PMID- 20132450
TI  - Life cycle studies of the hexose transporter of Plasmodium species and genetic
      validation of their essentiality.
AB  - A Plasmodium falciparum hexose transporter (PfHT) has previously been shown to be
      a facilitative glucose and fructose transporter. Its expression in Xenopus laevis
      oocytes and the use of a glucose analogue inhibitor permitted chemical validation
      of PfHT as a novel drug target. Following recent re-annotations of the P.
      falciparum genome, other putative sugar transporters have been identified. To
      investigate further if PfHT is the key supplier of hexose to P. falciparum and to
      extend studies to different stages of Plasmodium spp., we functionally analysed
      the hexose transporters of both the human parasite P. falciparum and the rodent
      parasite Plasmodium berghei using gene targeting strategies. We show here the
      essential function of pfht for the erythrocytic parasite growth as it was not
      possible to knockout pfht unless the gene was complemented by an episomal
      construct. Also, we show that parasites are rescued from the toxic effect of a
      glucose analogue inhibitor when pfht is overexpressed in these transfectants. We
      found that the rodent malaria parasite orthologue, P. berghei hexose transporter
      (PbHT) gene, was similarly refractory to knockout attempts. However, using a
      single cross-over transfection strategy, we generated transgenic P. berghei
      parasites expressing a PbHT-GFP fusion protein suggesting that locus is amenable
      for gene targeting. Analysis of pbht-gfp transgenic parasites showed that PbHT is
      constitutively expressed through all the stages in the mosquito host in addition
      to asexual stages. These results provide genetic support for prioritizing PfHT as
      a target for novel antimalarials that can inhibit glucose uptake and kill
      parasites, as well as unveiling the expression of this hexose transporter in
      mosquito stages of the parasite, where it is also likely to be critical for
      survival.

PMID- 20132451
TI  - The role of the FliK molecular ruler in hook-length control in Salmonella
      enterica.
AB  - A molecular ruler, FliK, controls the length of the flagellar hook. FliK measures
      hook length and catalyses the secretion-substrate specificity switch from rod
      hook substrate specificity to late substrate secretion, which includes the
      filament subunits. Here, we show normal hook-length control and filament assembly
      in the complete absence of the C-ring thus refuting the previous 'cup' model for
      hook-length control. Mutants of C-ring components, which are reported to produce
      short hooks, show a reduced rate of hook-basal body assembly thereby allowing for
      a premature secretion-substrate specificity switch. Unlike fliK null mutants,
      hook-length control in an autocleavage-defective mutant of flhB, the protein
      responsible for the switch to late substrate secretion, is completely abolished.
      FliK deletion variants that retain the ability to measure hook length are
      secreted thus demonstrating that FliK directly measures rod-hook length during
      the secretion process. Finally, we present a unifying model accounting for all
      published data on hook-length control in which FliK acts as a molecular ruler
      that takes measurements of rod-hook length while being intermittently secreted
      during the assembly process of the hook-basal body complex.

PMID- 20132452
TI  - Atomic force microscopy: probing the spatial organization, interactions and
      elasticity of microbial cell envelopes at molecular resolution.
AB  - Although much is known about the structure and biosynthesis of microbial cell
      envelope constituents, the three-dimensional organization, assembly and
      interactions of the individual components remain poorly understood. How do cell
      walls remodel during cell growth or incubation with drugs? What is the
      supramolecular architecture of proteins in bacterial surface layers, in outer
      membranes and in intracytoplasmic membranes? What is the spatial arrangement of
      cell surface receptors, clustered or homogeneous? What are the adhesive and
      mechanical properties of cell surface proteins and how are they related to
      function? Traditionally, these questions have been difficult - or impossible - to
      address owing to the lack of high-resolution single-cell and single-molecule
      probing techniques. With its ability to observe and force probe the cell envelope
      down to the molecular level under physiological conditions, atomic force
      microscopy (AFM) has recently offered new opportunities in molecular
      microbiology. While high-resolution AFM imaging is a powerful tool for
      visualizing the architecture of cells and membranes in buffer solution, force
      spectroscopy offers a means to analyse the localization, interactions and
      elasticity of their individual constituents. These nanoscale experiments
      complement microscopy, genetics and biochemical methods traditionally used to
      analyse the microbial envelope.

PMID- 20132453
TI  - Phosphatidylserine synthase and phosphatidylserine decarboxylase are essential
      for cell wall integrity and virulence in Candida albicans.
AB  - Phospholipid biosynthetic pathways play crucial roles in the virulence of several
      pathogens; however, little is known about how phospholipid synthesis affects
      pathogenesis in fungi such as Candida albicans. A C. albicans phosphatidylserine
      (PS) synthase mutant, cho1 Delta/Delta, lacks PS, has decreased
      phosphatidylethanolamine (PE), and is avirulent in a mouse model of systemic
      candidiasis. The cho1 Delta/Delta mutant exhibits defects in cell wall integrity,
      mitochondrial function, filamentous growth, and is auxotrophic for ethanolamine.
      PS is a precursor for de novo PE biosynthesis. A psd1 Delta/Delta psd2
      Delta/Delta double mutant, which lacks the PS decarboxylase enzymes that convert
      PS to PE in the de novo pathway, has diminished PE levels like those of the cho1
      Delta/Delta mutant. The psd1 Delta/Delta psd2 Delta/Delta mutant exhibits
      phenotypes similar to those of the cho1 Delta/Delta mutant; however, it is
      slightly more virulent and has less of a cell wall defect. The virulence losses
      exhibited by the cho1 Delta/Delta and psd1 Delta/Delta psd2 Delta/Delta mutants
      appear to be related to their cell wall defects which are due to loss of de novo
      PE biosynthesis, but are exacerbated by loss of PS itself. Cho1p is conserved in
      fungi, but not mammals, so fungal PS synthase is a potential novel antifungal
      drug target.

PMID- 20132454
TI  - Error-prone initiation factor 2 mutations reduce the fitness cost of antibiotic
      resistance.
AB  - Mutations in the fmt gene (encoding formyl methionine transferase) that eliminate
      formylation of initiator tRNA (Met-tRNA(i)) confer resistance to the novel
      antibiotic class of peptide deformylase inhibitors (PDFIs) while concomitantly
      reducing bacterial fitness. Here we show in Salmonella typhimurium that novel
      mutations in initiation factor 2 (IF2) located outside the initiator tRNA binding
      domain can partly restore fitness of fmt mutants without loss of antibiotic
      resistance. Analysis of initiation of protein synthesis in vitro showed that with
      non-formylated Met-tRNA(i) IF2 mutants initiated much faster than wild-type IF2,
      whereas with formylated fMet-tRNA(i) the initiation rates were similar. Moreover,
      the increase in initiation rates with Met-tRNA(i) conferred by IF2 mutations in
      vitro correlated well with the increase in growth rate conferred by the same
      mutations in vivo, suggesting that the mutations in IF2 compensate formylation
      deficiency by increasing the rate of in vivo initiation with Met-tRNA(i). IF2
      mutants had also a high propensity for erroneous initiation with elongator tRNAs
      in vitro, which could account for their reduced fitness in vivo in a formylation
      proficient strain. More generally, our results suggest that bacterial protein
      synthesis is mRNA-limited and that compensatory mutations in IF2 could increase
      the persistence of PDFI-resistant bacteria in clinical settings.

PMID- 20132455
TI  - Parental authority, nurturance, and two-dimensional self-esteem.
AB  - This study examined the relations of parental permissiveness, authoritativeness,
      authoritarianism, and nurturance with two dimensions of self-esteem - self-liking
      and self-competence. In a sample of 207 two-parent families, university students
      and both their parents provided independent reports on all the above variables.
      Covariance structure analysis was used to eliminate reporter-specific bias and
      unreliability in predicting student self-esteem from parenting behavior. The
      results revealed highly redundant positive associations of mothers' and fathers'
      authoritativeness and nurturance with both self-liking and self-competence. The
      pattern of these associations suggests that the significance of parental
      authoritativeness for the child's self-esteem is due mainly to the nurturance it
      provides. Contrary to expectation, mothers' and fathers' authoritarianism was
      also positively associated with self-liking. As discussed, however, this is
      likely to be an artifact of the specific measures and testing methods used.

PMID- 20132456
TI  - Anxiety disorders in 8-11-year-old children: motor skill performance and self
      perception of competence.
AB  - This study investigates motor skill performance and self-perceived competence in
      children with anxiety disorders compared with children without psychiatric
      disorders. Motor skills and self-perception were assessed in 329 children aged 8
      to 11 years, from the Bergen Child Study. The Kiddie-SADS PL diagnostic interview
      was employed to define a group of children with an anxiety disorder without
      comorbid diagnosis, and a control group (no diagnosis) matched according to
      gender, age, and full-scale IQ. Children in the anxiety disorder group displayed
      impaired motor skills and poor self-perceived peer acceptance and physical
      competence compared with the control group. Two-thirds of the anxious boys scored
      on the Motor Assessment Battery for Children (MABC) as having motor problems. The
      present study demonstrated impaired motor skills in boys with "pure" anxiety
      disorders. Anxious children also perceived themselves as being less accepted by
      peers and less competent in physical activities compared with children in the
      control group.

PMID- 20132457
TI  - Anger and hostility from the perspective of the Big Five personality model.
AB  - This study was aimed at examining the relationships of the personality dimensions
      of the five-factor model or Big Five with trait anger and with two specific
      traits of hostility (mistrust and confrontational attitude), and identifying the
      similarities and differences between trait anger and hostility in the framework
      of the Big Five. In a sample of 353 male and female adults, the Big Five
      explained a significant percentage of individual differences in trait anger and
      hostility after controlling the effects due to the relationship between both
      constructs and content overlapping across scales. In addition, trait anger was
      primarily associated with neuroticism, whereas mistrust and confrontational
      attitude were principally related to low agreeableness. These findings are
      discussed in the context of the anger-hostility-aggression syndrome and the
      capability of the Big Five for organizing and clarifying related personality
      constructs.

PMID- 20132458
TI  - Effectiveness in top management group meetings: the role of goal clarity, focused
      communication, and learning behavior.
AB  - To explore the relationship between goal clarity, focused communication, learning
      behavior, and team effectiveness (i.e., task performance, relationship quality,
      and member satisfaction), self-report and observer data from eight top management
      groups that processed 56 agenda items during meetings were analyzed. We found
      that goal clarity and focused communication was positively related to team
      effectiveness. The effect of goal clarity on team effectiveness was partially
      mediated by focused communication. Speaking up when a goal was unclear increased
      focused communication, task performance and relationship quality. Speaking up
      when the discussion was off track was not related to task performance and member
      satisfaction, and was negatively related to relationship quality. These findings
      have implications for how to conduct an effective management meeting.

PMID- 20132459
TI  - A facilitative effect of negative affective valence on working memory.
AB  - Previous studies have shown that negatively valenced information impaired working
      memory performance due to an attention-capturing effect. The present study
      examined whether negative valence could also facilitate working memory. Affective
      words (negative, neutral, positive) were used as retro-cues in a working memory
      task that required participants to remember colors at different spatial locations
      on a computer screen. Following the cue, a target detection task was used to
      either shift attention to a different location or keep attention at the same
      location as the retro-cue. Finally, participants were required to discriminate
      the cued color from a set of distractors. It was found that negative cues yielded
      shorter response times (RTs) in the attention-shift condition and longer RTs in
      the attention-stay condition, compared with neutral and positive cues. The
      results suggest that negative affective valence may enhance working memory
      performance (RTs), provided that attention can be disengaged.

PMID- 20132460
TI  - Mapping explicit social motives of achievement, power, and affiliation onto the
      five-factor model of personality.
AB  - Previous research has shown that explicit motives are meaningfully related to the
      five-factor model of personality. The present study extends this research by
      using different measures of the explicit social motives of achievement, power and
      affiliation, and by employing measures of both approach and avoidance of these
      motives. Correlational and factor analyses demonstrated that explicit motives of
      achievement, power, and affiliation, both approach and avoidance components of
      these motives, can be consistently mapped onto personality trait measures of the
      five-factor model. Implications of this general finding, along with some
      exceptions, are discussed with regard to further research.

PMID- 20132461
TI  - A mixed-method approach to sense of coherence, health behaviors, self-efficacy
      and optimism: towards the operationalization of positive health attitudes.
AB  - This study discusses the results of a cross-sectional survey of healthy college
      students in Poland. More specifically, it describes, explores, and explains the
      relationships between psychological variables/models such as health behaviors
      (HB), sense of coherence (SOC), level of optimism (LOO), and self-efficacy (SE)
      among college students. These separate constructs have also been used to
      operationalize a positive health attitude (PHA) as a novel construct. The social
      survey was carried out at three higher education institutions in Poland in
      January 2006. The random sample of 455 undergraduate students was taken from five
      different faculties: Physiotherapy, Physical Education, Tourism and Recreation,
      English Philology and Polish Philology. Four reliable and validated research
      tools were used to collect the data: Juczynsky's Health Behaviour Inventory
      (HBI); Antonovsky's Sense of Coherence Questionnaire (SOC-29); Schwarzer &
      Jerusalem's Generalized Self-Efficacy Scale (GSES); and Seligman's Scale (SS).
      The results indicate statistically significant differences (p < 0.001) between
      these four variables: for example, the healthier health behaviors the stronger
      the sense of coherence, level of optimism and self-efficacy. It was also
      demonstrated that LOO, SOC, SE, and HB correlate with one another. Finally, these
      variables create an explicit empirical-theoretical pattern. All the research
      results from REGWQ tests, Pearson's correlation coefficient and cluster analysis
      suggest the existence of conceptual similarities between these four variables
      and/or the existence of some broader scientific construct such as PHA. However,
      this needs to be examined further. These results could be a good indicator for
      future research among different faculties or age groups.

PMID- 20132462
TI  - Parenting practices and their relevance to child behaviors in Canada and China.
AB  - Recent studies have revealed that parents in different cultures endorse different
      child-rearing practices. Studies in the West suggest that there is a cluster of
      behavioral characteristics in children that are linked with each type of
      parenting styles. Mixed results, however, were found in non-Western countries.
      This study examined (1) parenting practices in Canadian and Chinese mothers, and
      (2) the relevance between parenting practices and child behaviors in Canada and
      China. Forty Canadian children (average age = 5.40) and 39 Chinese children
      (average age = 4.84) and their mothers participated in the study. Information on
      maternal authoritative and authoritarian behaviors and children's behaviors,
      including coercive request, polite request, and assertiveness, was obtained from
      observations of mother-child interactions in a laboratory situation. The results
      indicated that Chinese mothers were less authoritative and more authoritarian
      than Canadian mothers. Both cross-cultural differences and similarities were
      found on the associations between maternal parenting practices and child
      behaviors.

PMID- 20132463
TI  - Theory of mind and attentional bias to facial emotional expressions: a
      preliminary study.
AB  - Theory of mind ability has been associated with performance in interpersonal
      interactions and has been found to influence aspects such as emotion recognition,
      social competence, and social anxiety. Being able to attribute mental states to
      others requires attention to subtle communication cues such as facial emotional
      expressions. Decoding and interpreting emotions expressed by the face, especially
      those with negative valence, are essential skills to successful social
      interaction. The current study explored the association between theory of mind
      skills and attentional bias to facial emotional expressions. According to the
      study hypothesis, individuals with poor theory of mind skills showed preferential
      attention to negative faces over both non-negative faces and neutral objects.
      Tentative explanations for the findings are offered emphasizing the potential
      adaptive role of vigilance for threat as a way of allocating a limited capacity
      to interpret others' mental states to obtain as much information as possible
      about potential danger in the social environment.

PMID- 20132464
TI  - Effect of L-Dopa on metabotropic glutamate receptor 5 in the brain of
      parkinsonian monkeys.
AB  - Behavioral investigations of selective and potent metabotropic glutamate receptor
      type 5 (mGluR5) antagonists in animal models suggest involvement of mGluR5 in
      compensatory mechanisms of the basal ganglia circuitry in Parkinson's disease and
      levodopa (L-Dopa) induced motor complications. This study investigated mGluR5
      changes in MPTP lesioned monkeys. The effect of a chronic 1 month treatment with
      L-Dopa on mGluR5-specific binding and mRNA levels was investigated in MPTP
      monkeys killed 4 or 24 h after their last L-Dopa administration. [(3)H]ABP688
      specific binding in the putamen was elevated in L-Dopa-treated MPTP monkeys
      killed 24 h but not 4 h after their last L-Dopa dose compared with vehicle
      treated MPTP monkeys. Caudate nucleus [(3)H]ABP688-specific binding was elevated
      in both groups of L-Dopa treated compared with vehicle-treated MPTP monkeys. In
      contrast, caudate nucleus and putamen mGluR5 mRNA levels were elevated only in L
      Dopa-treated MPTP monkeys killed 4 h after their last L-Dopa administration. MPTP
      monkeys killed 4 h after their last L-Dopa treatment showed higher caudate
      nucleus and putamen L-Dopa concentrations compared with those killed after 24 h.
      Hence, mGluR5 in the putamen are sensitive to presence of L-Dopa leading to a
      rapid decrease of [(3)H]ABP688-specific binding possibly involving a direct
      mGluR5/dopamine receptors interaction.

PMID- 20132465
TI  - Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated
      calcium entry in motor neurones by increasing cell surface expression of the
      GluR2 subunit: relevance to neurodegeneration.
AB  - The alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)
      subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine
      tumour necrosis factor alpha (TNFalpha) have both been implicated in motor
      neurone vulnerability in amyotrophic lateral sclerosis/motor neurone disease.
      TNFalpha has been reported to increase cell surface expression of AMPAR subunits
      to increase synaptic strength and enhance excitotoxicity, but whether this
      mechanism occurs in motor neurones is unknown. We used primary cultures of mouse
      motor neurones and cortical neurones to examine the interaction between TNFalpha
      receptor activation, GluR2 availability, AMPAR-mediated calcium entry and
      susceptibility to excitotoxicity. Short exposure to a physiologically relevant
      concentration of TNFalpha (10 ng/mL, 15 min) caused a marked redistribution of
      both GluR1 and GluR2 to the cell surface as determined by cell surface
      biotinylation and immunofluorescence. Using fura-2-acetoxymethyl ester
      microfluorimetry, we showed that exposure to TNFalpha caused a rapid reduction in
      the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase
      dependent manner, consistent with increased insertion of GluR2-containing AMPAR
      into the plasma membrane. This resulted in a protection of motor neurones against
      kainate-induced cell death. Our data therefore, suggest that TNFalpha acts
      primarily as a physiological regulator of synaptic activity in motor neurones
      rather than a pathological drive in amyotrophic lateral sclerosis.

PMID- 20132466
TI  - NPY augments the proliferative effect of FGF2 and increases the expression of
      FGFR1 on nestin positive postnatal hippocampal precursor cells, via the Y1
      receptor.
AB  - We have shown that neuropeptide Y (NPY), a peptide neurotransmitter released by
      hippocampal interneurons, is proliferative for hippocampal neural stem progenitor
      cells (NSPCs) via the Y1 receptor. Fibroblast growth factor (FGF) 2, released
      predominantly by astrocytes, is also a powerful mitogen for postnatal and adult
      NSPCs, via the FGFR1 receptor. Knockout studies show that NPY and FGF2 are
      individually necessary, but not sufficient, for seizure-induced neurogenesis,
      suggesting a possible interaction. Here, we examined for interactions between NPY
      and FGF2 on NSPCs from the postnatal hippocampus and report that the combination
      of NPY and FGF2 significantly shortens the cell cycle time of nestin positive
      NSPCs, more than either factor alone. This augmentation of proliferation rate is
      NPY Y1 receptor mediated, and Y1 receptor activation increases both FGFR1 mRNA
      and protein in NSPC cultures. NSPCs immunostain for both Y1 and FGFR1 receptors
      and the interaction is specific for dentate NSPCs. This is the first report of a
      proliferative factor that augments the proliferative effect of FGF2 and is the
      first evidence of a positive proliferative interaction between a glial growth
      factor and a neuronal transmitter, identifying a novel neural activity driven
      mechanism for modulating the proliferation of hippocampal NSPCs.

PMID- 20132467
TI  - The Wld(S) mutation delays anterograde, but not retrograde, axonal degeneration
      of the dopaminergic nigro-striatal pathway in vivo.
AB  - For many neurodegenerative disorders, such as Parkinson's disease, there is
      evidence that the disease first affects axons and terminals of neurons that are
      selectively vulnerable. This would suggest that it may be possible to forestall
      progression by targeting the cellular mechanisms of axon degeneration. While it
      is now clear that these mechanisms are distinct from the pathways of programmed
      cell death, they are less well known. Compelling evidence of the distinctiveness
      of these mechanisms has derived from studies of the Wld(S) mutation, which
      confers resistance to axon degeneration. Little is known about how this mutation
      affects degeneration in dopaminergic axons, those that are affected in
      Parkinson's disease. We have characterized the Wld(S) phenotype in these axons in
      four models of injury: two that utilize the neurotoxin 6-hydroxydopamine or
      axotomy to induce anterograde degeneration, and two that use these methods to
      induce retrograde degeneration. For both 6-hydroxydopamine and axotomy, Wld(S)
      provides protection from anterograde, but not retrograde degeneration. This
      protection is observed as preserved immunostaining for tyrosine hydroxylase in
      axons and striatum, and by structural integrity visualized by GFP in tyrosine
      hydroxylase-GFP mice. Therefore, Wld(S) offers axon protection, but it reveals
      fundamentally different processes underlying antero- and retrograde degeneration
      in this system.

PMID- 20132468
TI  - Mitochondrial respiration and respiration-associated proteins in cell lines
      created through Parkinson's subject mitochondrial transfer.
AB  - Parkinson's disease (PD) is associated with perturbed mitochondrial function.
      Studies of cytoplasmic hybrid (cybrid) cell lines containing mitochondria from PD
      subjects suggest complex I dysfunction in particular is a relatively upstream
      biochemical defect. To evaluate potential downstream consequences of PD
      mitochondrial dysfunction, we used a cybrid approach to model PD mitochondrial
      dysfunction; our cybrid cell lines were generated via transfer of PD or control
      subject platelet mitochondria to mtDNA-depleted NT2 cells. To confirm our PD
      cybrid mitochondria did indeed differ from control cybrid mitochondria we
      measured complex I V(max) activities. Consistent with other PD cybrid reports,
      relative to control cybrid cell lines the PD cybrid cell line mean complex I
      V(max) activity was reduced. In this validated model, we used an oxygen electrode
      to characterize PD cybrid mitochondrial respiration. Although whole cell basal
      oxygen consumption was comparable between the PD and control cybrid groups, the
      proton leak was increased and maximum respiratory capacity was decreased in the
      PD cybrids. PD cybrids also had reduced SIRT1 phosphorylation, reduced peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha levels, and increased NF
      kB activation. We conclude mitochondrial respiration and pathways influenced by
      aerobic metabolism are altered in NT2 cybrid cell lines generated through
      transfer of PD subject platelet mitochondria.

PMID- 20132469
TI  - Curcumin attenuates cerebral edema following traumatic brain injury in mice: a
      possible role for aquaporin-4?
AB  - Traumatic brain injury is a devastating neurological injury associated with
      significant morbidity and mortality. Medical therapies to limit cerebral edema, a
      cause of increased intracranial hypertension and poor clinical outcome, are
      largely ineffective, emphasizing the need for novel therapeutic approaches. In
      the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 min post
      treatment with 300 mg/kg significantly reduced brain water content and improved
      neurological outcome following a moderate controlled cortical impact in mice. The
      protective effect of curcumin was associated with a significant attenuation in
      the acute pericontusional expression of interleukin-1beta, a pro-inflammatory
      cytokine, after injury. Curcumin also reversed the induction of aquaporin-4, an
      astrocytic water channel implicated in the development of cellular edema
      following head trauma. Notably, curcumin blocked IL-1beta-induced aquaporin-4
      expression in cultured astrocytes, an effect mediated, at least in part, by
      reduced activation of the p50 and p65 subunits of nuclear factor kappaB.
      Consistent with this notion, curcumin preferentially attenuated phosphorylated
      p65 immunoreactivity in pericontusional astrocytes and decreased the expression
      of glial fibrillary acidic protein, a reactive astrocyte marker. As a whole,
      these data suggest clinically achievable concentrations of curcumin reduce glial
      activation and cerebral edema following neurotrauma, a finding which warrants
      further investigation.

PMID- 20132470
TI  - TRP channels of intracellular membranes.
AB  - Ion channels are classically understood to regulate the flux of ions across the
      plasma membrane in response to a variety of environmental and intracellular cues.
      Ion channels serve a number of functions in intracellular membranes as well.
      These channels may be temporarily localized to intracellular membranes as a
      function of their biosynthetic or secretory pathways, i.e., en route to their
      destination location. Intracellular membrane ion channels may also be located in
      the endocytic pathways, either being recycled back to the plasma membrane or
      targeted to the lysosome for degradation. Several channels do participate in
      intracellular signal transduction; the most well known example is the inositol
      1,4,5-trisphosphate receptor (IP(3)R) in the endoplasmic reticulum. Some
      organellar intracellular membrane channels are required for the ionic homeostasis
      of their residing organelles. Several newly-discovered intracellular membrane
      Ca(2+) channels actually play active roles in membrane trafficking. Transient
      receptor potential (TRP) proteins are a superfamily (28 members in mammal) of
      Ca(2+)-permeable channels with diverse tissue distribution, subcellular
      localization, and physiological functions. Almost all mammalian TRP channels
      studied thus far, like their ancestor yeast TRP channel (TRPY1) that localizes to
      the vacuole compartment, are also (in addition to their plasma membrane
      localization) found to be localized to intracellular membranes. Accumulated
      evidence suggests that intracellularly-localized TRP channels actively
      participate in regulating membrane traffic, signal transduction, and vesicular
      ion homeostasis. This review aims to provide a summary of these recent works. The
      discussion will also be extended to the basic membrane and electrical properties
      of the TRP-residing compartments.

PMID- 20132471
TI  - Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal
      release of glutamate.
AB  - Pregabalin is an anti-convulsant that successfully treats many neuropathic pain
      syndromes, although the mechanism of its anti-hyperalgesic action remains
      elusive. This study aims to help delineate pregabalin's anti-hyperalgesic
      mechanisms. We assessed the effectiveness of pregabalin at decreasing mechanical
      and cold hypersensitivity induced in a rat model of neuropathic pain. Thus, we
      compared the effectiveness of pre- or post-treatment with systemic or intrathecal
      (i.t.) pregabalin at reducing the development and maintenance of the neuropathic
      pain symptoms. Pregabalin successfully decreased mechanical and cold
      hypersensitivity, as a pre-treatment, but was less effective at suppressing cold
      hypersensitivity when administered as a post-treatment. Furthermore, both i.t.
      and systemic administration of pregabalin were effective in reducing the
      behavioral hypersensitivity, with the exception of systemic post-treatment on
      cold hypersensitivity. We also examined pregabalin's effects at inhibiting hind
      paw formalin-induced nociception in naive rats and formalin-induced release of
      excitatory amino acids in the spinal cord dorsal horn (SCDH) both in naive rats
      and in rats with neuropathic pain. Pregabalin dose-dependently reduced
      nociceptive scores in the formalin test. We also present the first evidence that
      pregabalin reduces the formalin-induced release of glutamate in SCDH.
      Furthermore, i.t. pregabalin reduces the enhanced noxious stimulus-induced spinal
      release of glutamate seen in neuropathic rats. These data suggest that pregabalin
      reduces neuropathic pain symptoms by inhibiting the release of glutamate in the
      SCDH.

PMID- 20132472
TI  - Vital role of protein kinase C-related kinase in the formation and stability of
      neurites during hypoxia.
AB  - Exposure of pheochromocytoma cells to hypoxia (1% O(2)) favors differentiation at
      the expense of cell viability. Additional incubation with nerve growth factor
      (NGF) and guanosine, a purine nucleoside with neurotrophin characteristics,
      rescued cell viability and further enhanced the extension of neurites. In
      parallel, an increase in the activity of protein kinase C-related kinase (PRK1),
      which is known to be involved in regulation of the actin cytoskeleton, was
      observed in hypoxic cells. NGF and guanosine further enhanced PRK1 in normoxic
      and hypoxic cells. To study the role of PRK1 during cellular stress response and
      neurotrophin-mediated signaling, pheochromocytoma cells were transfected with
      small interfering RNA directed against PRK1. Loss of functional PRK1 initiated a
      significant loss of viability and inhibited neurite formation. SiRNA-mediated
      knockdown of PRK1 also completely stalled guanosine-mediated neuroprotective
      effects. Additionally, the F-actin-associated cytoskeleton and the expression of
      the plasticity protein growth associated protein-43 were disturbed upon PRK1
      knockdown. A comparable dependency of neurite formation and growth associated
      protein-43 immunoreactivity on functional PRK1 expression was observed in
      cerebellar granule neurons. Based on these data, a putative role of PRK1 as a key
      signaling element for the successive NGF- and purine nucleoside-mediated
      protection of hypoxic neuronal cells is hypothesized.

PMID- 20132473
TI  - Regulation of MCP-1 production in brain by stress and noradrenaline-modulating
      drugs.
AB  - While it is accepted that noradrenaline (NA) reduction in brain contributes to
      the progression of certain neurodegenerative diseases, the mechanisms through
      which NA exerts its protective actions are not well known. We previously reported
      that NA induced production of monocyte chemoattractant protein (MCP-1/CCL2) in
      cultured astrocytes mediated some of the neuroprotective actions of NA. We have
      now examined the regulation of MCP-1 production in vivo. Treatment of mice with
      the NA precursor l-threo-3,4-dihydroxyphenylserine induced the production of MCP
      1 in astrocytes. In contrast, exposure to stress (a process known to elevate
      brain NA levels) produced only a moderate increase of MCP-1 because of the
      inhibitory activity of glucocorticoids released during the stress response.
      Similarly, corticosterone treatment of astrocytes caused a reduction of
      constitutive as well as the NA-induced MCP-1 production. When stressed rats had
      the production of glucocorticoids blocked by the selective inhibitor metyrapone,
      a large increase of MCP-1 concentration was observed in cortex, whereas
      propranolol (a beta adrenergic receptor blocker) avoided modifications of MCP-1
      after stress. Desipramine (an inhibitor of NA reuptake) also caused an increase
      of MCP-1 in cortex. These data suggest that some phenomena caused by the
      alteration of NA or glucocorticoids could be mediated by MCP-1.

PMID- 20132475
TI  - Lactacidosis modulates glutathione metabolism and oxidative glutamate toxicity.
AB  - Lactate and acidosis increase infarct size in humans and in animal models of
      cerebral ischemia but the mechanisms by which they exert their neurotoxic effects
      are poorly understood. Oxidative glutamate toxicity is a form of nerve cell
      death, wherein glutamate inhibits cystine uptake via the cystine/glutamate
      antiporter system leading to glutathione depletion, accumulation of reactive
      oxygen species and, ultimately, programmed cell death. Using the hippocampal cell
      line, HT22, we show that lactate and acidosis exacerbate oxidative glutamate
      toxicity and further decrease glutathione levels. Acidosis but not lactate
      inhibits system , whereas both acidosis and lactate inhibit the enzymatic steps
      of glutathione synthesis downstream of cystine uptake. In contrast, when
      glutathione synthesis is completely inhibited by cystine-free medium, acidosis
      partially protects against glutathione depletion and cell death. Both effects of
      acidosis are also present in primary neuronal and astrocyte cultures.
      Furthermore, we show that some neuroprotective compounds are much less effective
      in the presence of lactacidosis. Our findings indicate that lactacidosis
      modulates glutathione metabolism and neuronal cell death. Furthermore,
      lactacidosis may interfere with the action of some neuroprotective drugs
      rendering these less likely to be therapeutically effective in cerebral ischemia.

PMID- 20132474
TI  - Noradrenaline activation of neurotrophic pathways protects against neuronal
      amyloid toxicity.
AB  - Degeneration of locus coeruleus (LC) noradrenergic forebrain projection neurons
      is an early feature of Alzheimer's disease. The physiological consequences of
      this phenomenon are unclear, but observations correlating LC neuron loss with
      increased Alzheimer's disease pathology in LC projection sites suggest that
      noradrenaline (NA) is neuroprotective. To investigate this hypothesis, we
      determined that NA protected both hNT human neuronal cultures and rat primary
      hippocampal neurons from amyloid-beta (Abeta(1-42) and Abeta(25-35)) toxicity.
      The noradrenergic co-transmitter galanin was also effective at preventing Abeta
      induced cell death. NA inhibited Abeta(25-35)-mediated increases in intracellular
      reactive oxygen species, mitochondrial membrane depolarization, and caspase
      activation in hNT neurons. NA exerted its neuroprotective effects in these cells
      by stimulating canonical beta(1) and beta(2) adrenergic receptor signaling
      pathways involving the activation of cAMP response element binding protein and
      the induction of endogenous nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF). Treatment with functional blocking antibodies for
      either NGF or BDNF blocked NA's protective actions against Abeta(1-42) and
      Abeta(25-35) toxicity in primary hippocampal and hNT neurons, respectively. Taken
      together, these data suggest that the neuroprotective effects of noradrenergic LC
      afferents result from stimulating neurotrophic NGF and BDNF autocrine or
      paracrine loops via beta adrenoceptor activation of the cAMP response element
      binding protein pathway.

PMID- 20132476
TI  - Insulin inhibits Abeta fibrillogenesis through a decrease of the GM1 ganglioside
      rich microdomain in neuronal membranes.
AB  - Type 2 diabetes is a risk factor for late-onset Alzheimer's disease. However, the
      underlying mechanisms remain unknown. To investigate whether insulin is
      associated with the assembly of amyloid beta-protein from the cell surface, we
      treated nerve growth factor (NGF)-treated rat pheochromocytoma 12 (PC12) cells
      with insulin, which is related to the development of diabetes. Insulin treatment
      induced a decrease in GM1 ganglioside (GM1) levels in detergent-resistant
      membrane microdomains of NGF-treated PC12 cells. The insulin-induced effects on
      GM1 levels were regulated by a phosphatidylinositol 3-kinase inhibitor, but not
      by an extracellular signal-regulated kinase inhibitor. Pre-treatment with a
      protein synthesis inhibitor did not inhibit the decrease in GM1 levels induced by
      insulin. In addition, insulin failed to induce formation of fibrils from soluble
      amyloid beta-protein or to accelerate GM1-induced fibril formation. Furthermore,
      assembly of amyloid beta-protein in cultures of NGF-treated PC12 cells was
      significantly decreased by insulin. These results suggest that insulin inhibits
      amyloid beta-protein assembly by decreasing GM1 expression in detergent-resistant
      membrane microdomains of neuronal membranes.

PMID- 20132478
TI  - In vitro activation of GAT1 transporters expressed in spinal cord gliosomes
      stimulates glutamate release that is abnormally elevated in the SOD1/G93A(+)
      mouse model of amyotrophic lateral sclerosis.
AB  - The effect of GABA on glutamate release from astrocytes has been studied in
      healthy mice and in a murine transgenic model of amyotrophic lateral sclerosis
      (ALS), using mouse spinal cord gliosomes labeled with [(3)H]d-aspartate ([(3)H]d
      ASP). GABA concentration-dependently evoked the release of [(3)H]d-ASP. The
      effect of GABA was not mimicked by GABA(A) or GABA(B) receptor agonists or
      counteracted by antagonists, excluding receptor involvement. However, it was
      prevented by the GABA transport inhibitor N-(4,4-phenyl-3-butenyl)-nipecotic acid
      (SKF 89976A), suggesting participation of GABA transporters type 1 (GAT1) placed
      on glutamate-releasing astrocyte-derived gliosomes. Accordingly, GAT1 co
      expressed with glutamate-aspartate transporter (GLAST) and glutamate transporter
      type 1 (GLT1) in the majority of glial particles. [(3)H]d-aspartate release was
      Ca(2+)-independent and not blocked by the glutamate uptake inhibitor dl-threo-b
      benzyloxyaspartic acid (dl-TBOA); instead, it was abrogated by the anion channel
      blockers niflumic acid and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB).
      The GAT1-mediated release of [(3)H]d-ASP was significantly enhanced in spinal
      cord gliosomes from the mouse model of ALS. This excessive [(3)H]d-ASP release
      was very precocious, largely preceding the onset of the disease symptoms. These
      data indicate that GAT1, GLAST and GLT1 coexist on the same gliosome in mouse
      spinal cord and that activation of GAT1 transporters elicits glutamate release by
      anion channel opening. This phenomenon might have pathological relevance, because
      [(3)H]d-ASP release is enhanced in experimental ALS.

PMID- 20132479
TI  - Development of a novel therapy for Lipo-oligosaccharide-induced experimental
      neuritis: use of peptide glycomimics.
AB  - Recent etiological studies have revealed that molecular mimicry between the lipo
      oligosaccharide (LOS) component of Campylobacter jejuni and gangliosides of
      peripheral nervous system plays an important role in the pathogenesis of Guillain
      Barre syndrome (GBS). Previously, we demonstrated GD3 ganglioside molecular
      mimicry in a model of GBS in Lewis rats by sensitization with GD3-like LOS
      (LOS(GD3)) from C. jejuni. Since the neuropathophysiological consequences were
      due largely to the anti-GD3-like antibodies, we subsequently focused our effort
      upon eliminating the pathogenic antibodies using several strategies to mimic GD3
      in this model. Here, we have validated this strategy by the use of peptide
      glycomimics based on epitopic mimicry between carbohydrates and peptides. We
      treated rats by i.p. administration of phage-displayed GD3-like peptides. One GD3
      like peptide (P(GD3)-4; RHAYRSMAEWGFLYS) induced in treated rats a remarkable
      restoration of motor nerve functions, as evidenced by improved histopathology,
      rotarod performance, and motor nerve conduction velocity. P(GD3)-4 effectively
      decreased the titer of anti-GD3/anti-LOS(GD3) antibodies and ameliorated
      peripheral nerve dysfunction in the sera of treated rats. The data suggest that
      peptide glycomimics of ganglioside may be potential powerful reagents for
      therapeutic intervention in GBS by neutralizing specific pathogenic anti
      ganglioside antibodies.

PMID- 20132480
TI  - Phosphoinositide 3-kinase mediated signaling in lobster olfactory receptor
      neurons.
AB  - In vertebrates and some invertebrates, odorant molecules bind to G protein
      coupled receptors on olfactory receptor neurons (ORNs) to initiate signal
      transduction. Phosphoinositide 3-kinase (PI3K) activity has been implicated
      physiologically in olfactory signal transduction, suggesting a potential role for
      a G protein-coupled receptor-activated class I PI3K. Using isoform-specific
      antibodies, we identified a protein in the olfactory signal transduction
      compartment of lobster ORNs that is antigenically similar to mammalian PI3Kgamma
      and cloned a gene for a PI3K with amino acid homology with PI3Kbeta. The lobster
      olfactory PI3K co-immunoprecipitates with the G protein alpha and beta subunits,
      and an odorant-evoked increase in phosphatidylinositol (3,4,5)-trisphosphate can
      be detected in the signal transduction compartment of the ORNs. PI3Kgamma and
      beta isoform-specific inhibitors reduce the odorant-evoked output of lobster ORNs
      in vivo. Collectively, these findings provide evidence that PI3K is indeed
      activated by odorant receptors in lobster ORNs and further support the potential
      involvement of G protein activated PI3K signaling in olfactory transduction.

PMID- 20132481
TI  - Tyrosine phosphatases Shp1 and Shp2 have unique and opposing roles in
      oligodendrocyte development.
AB  - Oligodendrocyte progenitor cells first proliferate to generate sufficient cell
      numbers and then differentiate into myelin-producing oligodendrocytes. The signal
      transduction mediators that underlie these events, however, remain poorly
      understood. The tyrosine phosphatase Shp1 has been linked to oligodendrocyte
      differentiation as Shp1-deficient mice show hypomyelination. The Shp1 homolog,
      Shp2, has recently been shown to regulate astrogliogenesis, but its role in
      oligodendrocyte development remains unknown. Here, we report that Shp2 protein
      levels were developmentally regulated in oligodendrocytes, with Shp2
      phosphorylation being promoted by oligodendroglial mitogens but suppressed by
      laminin, an extracellular matrix protein that promotes oligodendroglial
      differentiation. In contrast, oligodendrocyte progenitors were found to be
      unresponsive to mitogens following Shp2, but not Shp1, depletion. In agreement
      with previous studies, Shp1 depletion led to decreased levels of myelin basic
      protein in differentiating oligodendrocytes, as well as reduced outgrowth of
      myelin membrane sheets. Shp2 depletion in contrast did not prevent
      oligodendrocyte differentiation but promoted expanded myelin membrane outgrowth.
      Taken together these data suggest that Shp1 and Shp2 have distinct functions in
      oligodendrocyte development: Shp2 regulates oligodendrocyte progenitor
      proliferation and Shp1 regulates oligodendrocyte differentiation. Adhesion to
      laminin may additionally provide extrinsic regulation of Shp2 activity and thus
      promote the transition from progenitor to differentiating oligodendrocyte.

PMID- 20132482
TI  - Microglial C5aR (CD88) expression correlates with amyloid-beta deposition in
      murine models of Alzheimer's disease.
AB  - Alzheimer's disease (AD), a progressive neurodegenerative disease characterized
      by the accumulation of amyloid-beta protein and neuronal loss, is the leading
      cause of age-related dementia in the world today. The disease is also associated
      with neuroinflammation, robust activation of astrocytes and microglia, and
      evidence of activation of the complement system, localized with both fibrillar
      amyloid-beta (fAbeta) plaques and tangles. The observations are consistent with a
      complement-dependent component of AD progression. We have previously shown that
      inhibition of the major complement receptor for C5a (CD88) with the antagonist
      PMX205 results in a significant reduction in pathology in two mouse models of AD.
      To further characterize the role of complement in AD-related neuroinflammation,
      we examined the age- and disease-associated expression of CD88 in brain of
      transgenic mouse models of AD and the influence of PMX205 on the presence of
      various complement activation products using flow cytometry, western blot, and
      immunohistochemistry. CD88 was found to be up-regulated in microglia, in the
      immediate vicinity of amyloid plaques. While thioflavine plaque load and glial
      recruitment is significantly reduced after treatment with PMX205, C1q remains co
      localized with fAbeta plaques and C3 is still expressed by the recruited
      astrocytes. Thus, with PMX205, potentially beneficial activities of these early
      complement components may remain intact, while detrimental activities resulting
      from C5a-CD88 interaction are inhibited. This further supports the targeted
      inhibition of specific complement mediated activities as an approach for AD
      therapy.

PMID- 20132483
TI  - Mutant SOD1 knockdown in all cell types ameliorates disease in G85R SOD1 mice
      with a limited additional effect over knockdown restricted to motor neurons.
AB  - Approximately 10% of patients with amyotrophic lateral sclerosis (ALS) have
      familial ALS (FALS), and 20% of FALS is caused by mutant Cu/Zn superoxide
      dismutase type 1 (MTSOD1). Previous studies have convincingly demonstrated that
      MTSOD1 expression in other cell types besides motor neurons (MNs) contributes to
      disease in MTSOD1 FALS transgenic mice. Using Cre/LoxP methods, we knocked down
      G85R SOD1 mRNA by 66% in all cell types in 3-month-old FALS transgenic mice,
      delaying disease onset and lengthening disease duration. Surprisingly, the effect
      on onset and early disease duration was similar to that seen in FALS transgenic
      mice with approximately 25% knockdown prenatally in G85R SOD1 mRNA restricted to
      MNs and some interneurons. These results demonstrate no clear cumulative effect
      on disease onset or early disease duration from knocking down G85R SOD1 in other
      cell types in addition to MNs/interneurons; the findings bring up the possibility
      that MTSOD1 has a pathogenic effect early in life that our later knockdown did
      not affect. Despite the more limited amelioration of disease than expected, the
      effect of the knockdown on disease supports the value of this approach in FALS
      patients and asymptomatic individuals with SOD1 mutations.

PMID- 20132484
TI  - Transgene-mediated GDNF expression enhances synaptic connectivity and GABA
      transmission to improve functional outcome after spinal cord contusion.
AB  - Glial cell line-derived trophic factor (GDNF) is a peptide with pleiotropic
      survival and growth-promoting effects on neurons. We found that intraspinal
      injection of a non-replicating herpes simplex virus-based vector coding for GDNF
      2 h after blunt trauma to the thoraco-lumbar spinal cord produced sustained
      improvement in motor behavioral outcomes up to 5 weeks following injury. The
      improvement in behavior correlated with an increase in synaptophysin and glutamic
      acid decarboxylase (GAD) in the spinal cord at the level of injury. Addition of
      recombinant GDNF protein to primary spinal cord neurons in-vitro resulted in
      enhanced neurite growth and a marked increase in protein levels of GAD65 and
      GAD67, synapsin I and synaptophysin. GDNF-mediated increases in GAD and the
      synaptic markers were blocked by the MEK inhibitor UO126, but not by the
      phosphoinositide 3-kinase inhibitor LY294002. These results suggest that GDNF,
      acting through the MEK-ERK pathway enhances axonal sprouting, synaptic
      connectivity, and GABAergic neurotransmission in the spinal cord, that result in
      improved behavioral outcomes after spinal cord contusion injury.

PMID- 20132485
TI  - A novel, high-efficiency cellular model of fibrillar alpha-synuclein inclusions
      and the examination of mutations that inhibit amyloid formation.
AB  - Intracytoplasmic alpha-synuclein (alpha-syn) amyloidogenic inclusions are a major
      pathological feature of Parkinson's disease, dementia with Lewy body disease and
      multiple systems atrophy. The mechanisms involved in the formation and inhibition
      of these aggregates are areas of intense investigation. The present study
      characterizes a novel cellular model for the study of alpha-syn aggregation,
      incorporating nucleation-dependent aggregation and a new function for calcium
      phosphate precipitation. Cultured cells were readily induced to develop large,
      cytoplasmic alpha-syn filamentous aggregates that were hyperphosphorylated, often
      ubiquitinated and thioflavin positive. These cellular aggregates formed in the
      majority of transfected cells and recruited approximately half of endogenously
      expressed alpha-syn. Using this system, we examined single-point mutations that
      inhibit alpha-syn amyloid formation in vitro. Three mutations (V66P, T72P and
      T75P) significantly hindered alpha-syn aggregation in this cell model. The T75P
      mutant, which could abrogate amyloid formation of wild-type alpha-syn in vitro,
      did not prevent wild-type alpha-syn cellular aggregates. These studies suggest
      that the propensity of alpha-syn to form cellular aggregates may be more
      pronounced than in isolated in vitro studies. This novel high-efficiency cellular
      model of alpha-syn aggregation is a valuable system that may be used to further
      understand alpha-syn aggregation and allow for the generation of future
      therapeutics.

PMID- 20132486
TI  - Inhibition of histone deacetylases in rats self-administering cocaine regulates
      lissencephaly gene-1 and reelin gene expression, as revealed by microarray
      technique.
AB  - Injection of the histone deacetylase inhibitor trichostatin A (TsA) to rats has
      been shown to decrease their motivation to self-administer cocaine. In the
      present study, we investigated alterations in gene expression patterns in the
      anterior cingulate cortex and nucleus accumbens of rats self-administering
      cocaine and treated with TsA. Using oligonucleotide microarrays, we identified
      722 probe sets in the cortex and 136 probe sets in the nucleus accumbens that
      were differentially expressed between vehicle and TsA-treated rats that self
      administered cocaine. Microarray data were validated by real-time PCR for seven
      genes. Using immunohistochemistry, we further investigated the expression of Lis1
      and reelin genes, because (i) they were similarly regulated by TsA at the mRNA
      level; (ii) they belong to the same signal transduction pathway; (iii) mutations
      within both genes cause lissencephaly. Cocaine self-injection was sufficient to
      activate the two genes at both the mRNA and protein levels. TsA treatment was
      found to up-regulate both Lis1 and reelin protein expression in the cortex and to
      down-regulate it in the nucleus accumbens of rats self-administering cocaine. The
      data suggest that the two proteins contribute to establish neurobiological
      mechanisms underlying brain plasticity whereby TsA lowers the motivation for
      cocaine.

PMID- 20132487
TI  - Function of dopamine transporter is compromised in DYT1 transgenic animal model
      in vivo.
AB  - Early onset torsion dystonia (DYT1), the most common form of hereditary primary
      dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein,
      torsinA. We previously examined the effect of the human mutant torsinA on
      striatal dopaminergic function in a conventional transgenic mouse model of DYT1
      dystonia (hMT1), in which human mutant torsinA is expressed under the
      cytomegalovirus promotor. Systemic administration of amphetamine did not increase
      dopamine (DA) release as efficiently in these mice as compared with wild-type
      transgenic and non-transgenic mice. We, now, studied the contribution of the DA
      transporter (DAT) to amphetamine-induced DA release in hMT1 transgenic mice using
      in vivo no-net flux microdialysis. This method applies different concentrations
      of DA through the microdialysis probe and measures DA concentration at the output
      of the probe following an equilibrium period. The slope (extraction fraction) is
      the measure of the DAT activity in vivo. The slope for hMT1 transgenic mice was
      0.58 +/- 0.07 and for non-transgenic animals, 0.87 +/- 0.06 (p < 0.05). We
      further investigated the efficacy of nomifensine (a specific DAT inhibitor) in
      inhibiting amphetamine-induced DA release. Local application of nomifensine 80
      min before the systemic application of amphetamine inhibited DA release in both
      transgenic mice and their non-transgenic littermates. The efficiency of the
      inhibition appeared to be different, with mean values of 48% for hMT1 transgenic
      mice versus 84% for non-transgenic littermates. Moreover, we have evaluated basal
      and amphetamine-induced locomotion in hMT1 transgenic mice compared with their
      non-transgenic littermates, using an O-maze behavioral chamber. Basal levels of
      locomotion in the hMT1 transgenic mice showed that they moved much less than
      their non-transgenic littermates (0.9 +/- 0.3 m for transgenic mice vs. 2.4 +/-
      0.7 m for non-transgenic littermates, p < 0.05). This relative reduction in
      locomotion was also observed following amphetamine administration (48.5 +/- 6.7 m
      for transgenics vs. 73.7 +/- 9.8 m for non-transgenics, p < 0.05). These results
      support the finding that there are altered dynamics of DA release and reuptake in
      hMT1 transgenic mice in vivo, with DAT activity is reduced in the presence of
      mutant torsinA, which is consistent with behavioral consequences such as reduced
      locomotion and (previously described) abnormal motor phenotypes such as increased
      hind-base width and impaired performance on the raised-beam task. These data
      implies that altered DAT function may contribute to impaired DA neurotransmission
      and clinical symptoms in human DYT1 dystonia.

PMID- 20132488
TI  - Molecular genetic and epigenetic analysis of NCX2/SLC8A2 at 19q13.3 in human
      gliomas.
AB  - AIM: Loss of heterozygosity at 19q13.3 is a common genetic change in human
      gliomas, indicating yet unknown glial-specific tumour suppressor genes in this
      chromosome region. NCX2/SLC8A2 located on chromosome 19q13.32 encodes a
      Na(+)/Ca(2+) exchanger, which contributes to intracellular Ca(2+) homeostasis.
      Its expression is restricted to brain, and it is present neither in other normal
      tissues nor in gliomas at any significant level. The aim of this study was to
      investigate if NCX2 might be a tumour suppressor gene involved in glioma.
      METHODS: We performed a systematic analysis of NCX2 in 42 human gliomas using
      microsatellite analysis for evaluation of loss of heterozygosity at 19q, DNA
      sequencing and DNA methylation analysis. RESULTS: Except for three known
      intragenic single nucleotide polymorphisms, rs12459087, rs7259674 and rs8104926,
      no NCX2 sequence variations were detected in any of the tumour samples.
      Furthermore, a CpG island in the 5' promoter region of NCX2 was unmethylated.
      Interestingly, the CpG sites of three gene-body CpG islands located in exon 2,
      intron 2-3 and exon 3 and of a 5' CpG-rich area relevant to so-called CpG island
      shore of NCX2 were methylated in all eight glioma samples and in three
      established glioma cell lines tested. Surprisingly, NCX2 could be activated by
      addition of the DNA methylation inhibitor 5-aza-2'-deoxycytidine to glioma cell
      lines in which NCX2 was completely silent. CONCLUSION: Results indicate that DNA
      methylation may play a key role in the transcriptional silencing of NCX2.

PMID- 20132489
TI  - Analysis of beta-amyloid (Abeta) deposition in the temporal lobe in Alzheimer's
      disease using Fourier (spectral) analysis.
AB  - AIM: To determine the spatial pattern of beta-amyloid (Abeta) deposition
      throughout the temporal lobe in Alzheimer's disease (AD). METHODS: Sections of
      the complete temporal lobe from six cases of sporadic AD were immunolabelled with
      antibody against Abeta. Fourier (spectral) analysis was used to identify
      sinusoidal patterns in the fluctuation of Abeta deposition in a direction
      parallel to the pia mater or alveus. RESULTS: Significant sinusoidal fluctuations
      in density were evident in 81/99 (82%) analyses. In 64% of analyses, two
      frequency components were present with density peaks of Abeta deposits repeating
      every 500-1000 microm and at distances greater than 1000 microm. In 25% of
      analyses, three or more frequency components were present. The estimated period
      or wavelength (number of sample units to complete one full cycle) of the first
      and second frequency components did not vary significantly between gyri of the
      temporal lobe, but there was evidence that the fluctuations of the classic
      deposits had longer periods than the diffuse and primitive deposits. CONCLUSIONS:
      (i) Abeta deposits exhibit complex sinusoidal fluctuations in density in the
      temporal lobe in AD; (ii) fluctuations in Abeta deposition may reflect the
      formation of Abeta deposits in relation to the modular and vascular structure of
      the cortex; and (iii) Fourier analysis may be a useful statistical method for
      studying the patterns of Abeta deposition both in AD and in transgenic models of
      disease.

PMID- 20132490
TI  - Secreted protein, acidic and rich in cysteine (SPARC) expression in astrocytic
      tumour cells negatively correlates with proliferation, while vascular SPARC
      expression is associated with patient survival.
AB  - AIMS: Secreted protein, acidic and rich in cysteine (SPARC) is a regulator of
      cell-matrix interaction and has been associated with tumour stage and patient
      survival in various malignancies. As no large-scale study has yet been
      undertaken, we investigated human brain and astrocytomas for SPARC expression and
      associations with tumour grade, proliferation, vascular density and patient
      survival. METHODS: A spectrum of 188 WHO grade I-IV astrocytic tumours and 24
      autopsy cases were studied by immunohistochemistry for SPARC, MIB-1 proliferation
      index and CD31-positive vessels. SPARC protein expression was confirmed by
      quantitative real-time polymerase chain reaction and Western blot in 13 cases.
      RESULTS: In normal brain, SPARC is expressed in cortical marginal glia,
      cerebellar Bergmann glia and focally in white matter but is absent in neurones or
      vessels. High SPARC expression levels in the cytoplasm of astrocytic tumour cells
      decreased with the grade of malignancy but showed an increase with grade of
      malignancy in tumour vessels. SPARC negatively correlated with tumour
      proliferation but not with vascular density. While cytoplasmic SPARC staining was
      not associated with survival, vascular SPARC showed a significant association in
      the group of grade II-IV tumours (P = 0.02) and also in grade II astrocytomas
      alone (P = 0.01) with vascular SPARC associated with worse prognosis.
      CONCLUSIONS: SPARC is highly expressed in astrocytomas and decreases with tumour
      progression. We confirm an association of increased SPARC expression and
      decreased proliferation. While there is no association between the level of SPARC
      in the tumour cells and patient survival, increased tumour vascular SPARC
      expression is associated with decreased patient survival.

PMID- 20132491
TI  - Sensing performance of a new wireless implantable loop recorder: a 12-month
      follow up study.
AB  - BACKGROUND: The implantable loop recorder (ILR) is a cost-effective tool with a
      high diagnostic yield in the evaluation of unexplained recurrent syncope. The
      Sleuth ILR (Transoma Medical, St. Paul MN, USA) is a new-generation ILR with
      wireless transmission capability approved by the Food and Drug Administration. We
      report the feasibility of achieving appropriate sensing over 1-year follow-up at
      the traditional midclavicular and alternative inframammary implantation sites
      without preimplant electrocardiogram (ECG) mapping. METHODS AND RESULTS: We
      studied 32 patients with unexplained syncope, aged 58.4+/-18.44 years, with an
      ILR implanted at the left midclavicular location (n = 17) or the left
      inframammary site (n = 15) over 1-year post implant. No preimplant
      electrocardiogram (ECG) mapping was performed. The highest R-wave amplitudes were
      observed at the inframammary site, but over the entire follow-up period,
      amplitudes were not significantly different from those at the midclavicular site.
      At both sites, R-wave amplitudes at the 6-month follow-up were significantly
      higher than those measured at 1 week. P-waves were visible in 80-90% of the
      patients. There was no discernible difference in P-waves (amplitude) relative to
      implant location. Body mass index, left ventricular ejection fraction, and age
      did not significantly influence the R-wave amplitude or the ability to discern P
      waves. CONCLUSION: Our findings show that the Sleuth ILR implanted at both the
      midclavicular and inframammary locations without preimplant ECG mapping achieves
      acceptable "R" waves. This may simplify implantation procedures and improve
      patient satisfaction.

PMID- 20132492
TI  - The effects of temperature on cardiac pacing thresholds.
AB  - BACKGROUND: Human core body temperature can fluctuate between 36 degrees C
      (sleep) and 42 degrees C (intense exercise). Also, efforts are underway to
      develop implantable pacing systems that minimize heating during magnetic
      resonance imaging (MRI) scans (i.e., MRI safe). Concerns exist that ventricular
      pacing capture thresholds (VPCT) are modified by changing cardiac temperatures.
      This project was designed to assess the effects of temperature on VPCT of the
      mammalian heart. METHODS: Fresh ventricular specimens were obtained from healthy
      canine, healthy swine, and diseased human hearts. Isolated trabeculae were
      suspended in temperature-controlled tissue baths containing oxygenated Krebs
      buffer. Small active fixation pacing leads delivered pacing pulses to each
      specimen. Baseline strength-duration curves were determined at 37 degrees C, then
      at randomized temperatures ranging from 35 degrees C to 42 degrees C. Final
      thresholds were repeated at 37 degrees C to confirm baseline responses. All
      threshold data were normalized to a baseline average. RESULTS: Both canine and
      swine trabeculae elicited significant decreases in thresholds (10-14%) at pacing
      stimulus durations (pulsewidths) of 0.02 ms (P < 0.01) and 0.10 ms (P < 0.05)
      between the temperatures of 38 degrees C and 41 degrees C, compared to baseline.
      Thresholds at 42 degrees C trended back to baseline for both canine (NS) and
      swine trabeculae (P < 0.05 compared to 38 degrees C-41 degrees C). Human
      trabeculae thresholds increased >35% (P < 0.05) at 42 degrees C relative to
      baseline with no significant differences at other temperatures. CONCLUSIONS:
      Temperature is a significant factor on pacing thresholds for mammalian
      ventricular myocardium. Our data for the diseased human trabeculae indicate that
      cases where cardiac heating may occur (e.g., radiofrequency energy due to MRI
      scans, febrile events), patients without adequate VPCT safety margin may be at
      higher risk of loss of proper function of an implanted pacing or defibrillation
      system.

PMID- 20132493
TI  - Utility and safety of axillo-subclavian venous imaging with carbon dioxide (CO)
      prior to chronic lead system revisions.
AB  - BACKGROUND: Prior to attempting placement of one or more electrodes to revise
      existing rhythm control devices, patency of the central veins should be
      documented, in view of a high incidence of significant chronic occlusions. Since
      iodinated contrast venography may be contraindicated in select situations,
      imaging of the axillo-subclavian venous system with gaseous carbon dioxide
      (CO(2)) was evaluated prospectively in 23 consecutive individuals who were
      considered for revision of previously implanted pacemaker or automatic
      cardioverter defibrillator lead systems. METHODS: Approximately 20 mL of CO(2)
      were manually infused via CO(2) primed injection tubing into a vein at or above
      the level of the antecubital fossa ipsilateral to the side of prior lead
      placements. Digital subtraction imaging over the axillo-subclavian region, lower
      neck, and mediastinum was performed. Formal interpretation was obtained from one
      of three interventional radiologists and at least one electrophysiologist.
      RESULTS: Significant venous occlusions were identified in five (22%) patients.
      Vascular access utilized for the subsequent 18 revisions performed included the
      imaged patent ipsilateral vein in 14 patients and the contralateral, right-sided
      subclavian venous system in three patients. One patient required epicardial left
      ventricular lead placement. There were no complications from venography.
      CONCLUSIONS: Axillo-subclavian venography with gaseous CO(2) in patients
      undergoing pacemaker or implantable cardioverter defibrillator lead revisions is
      feasible and safe when use of iodinated dye is contraindicated. This technique
      should be employed in patients with azotemia, dye contrast allergies, or
      significant inflammation in the vicinity of the intravenous line insertion.

PMID- 20132494
TI  - Ablation of left ventricular tachycardia via transeptal approach and crossing of
      a mechanical mitral valve prosthesis.
AB  - This report describes the clinical course of a patient with left ventricular
      assist device (LVAD) and refractory ventricular tachycardia (VT) who underwent
      successful left ventricular (LV) mapping and ablation complicated by the presence
      of a bioprosthetic aortic and a mechanical mitral valve. LV catheterization was
      achieved by crossing the mechanical valve. The patient remained hemodynamically
      stable during the procedure most likely as a result of LVAD support. There were
      no complications. A recurrence of monomorphic VT 2 months later required a second
      VT ablation procedure using the same transseptal-transmitral approach. The
      patient has since been free of implantable cardioverter defibrillator shocks for
      2 months since the second procedure.

PMID- 20132498
TI  - The terms "chronaxie" and "rheobase" are 100 years old.

PMID- 20132499
TI  - Transthoracic sensor for noninvasive assessment of left ventricular
      contractility: validation in a minipig model of chronic heart failure.
AB  - BACKGROUND: Invasively measured left ventricular (LV) dP/dt is the accepted
      standard for measuring acute and chronic directional changes in LV contractility.
      Recently, we developed a noninvasive force sensor based on an accelerometer
      positioned on the chest, which measures the vibrations generated by isovolumic
      myocardial contraction. The aim of this paper was to compare noninvasive
      (accelerometer) versus invasive (LV dP/dt) indices of myocardial contractility in
      a chronic minipig model of pacing-induced heart failure (HF). Comparative
      assessment was performed both at rest and following dobutamine infusion. METHODS:
      In adult male minipigs (n = 6), LV contractility was simultaneously assessed both
      invasively (LV dP/dt, Millar catheter) and noninvasively (accelerometer) at rest
      and following dobutamine (up to 7.5 mcg/kg/min), both before and after
      development of HF by pacing the LV at 180 beats/min for 3 weeks. RESULTS:
      Invasive and noninvasive assessments were obtained in 24 conditions (12 at rest
      and 12 after dobutamine infusion). Sensor-based cardiac force changes were
      significantly related to positive peak LV dP/dt(max) changes following dobutamine
      infusion both in normal (r = 0.88, P < 0.001) and failing heart (r = 0.89, P <
      0.001). The force-frequency relation showed a tight correlation between invasive
      and noninvasive assessment (r = 0.68, P = 0.02). CONCLUSIONS: The force-frequency
      relation can be assessed noninvasively by a transthoracic sensor based on an
      accelerometer. The method can efficiently detect the development of resting
      dysfunction and the contractile reserve at different HF steps, with potential for
      wearable HF monitoring.

PMID- 20132500
TI  - Perioperative management of anticoagulation during device implantation-the UK
      perspective.
AB  - BACKGROUND: Increasing numbers of patients taking oral anticoagulation are
      presenting for device implantation. Cessation of anticoagulation in the
      perioperative period may expose patients to increased risk of thromboembolic
      events, while continuing anticoagulation may increase the risk of bleeding. There
      are few guidelines or randomized controlled trials to guide perioperative
      management. METHODS: We carried out a questionnaire-based study of all
      cardiologists implanting devices in the United Kingdom to establish if there was
      consensus on management of anticoagulation in patients undergoing pacemaker
      implantation. RESULTS: There is significant variation in management of these
      patients. Eighty-nine percent of doctors stop oral anticoagulation a mean 3.7
      days prior to pacemaker implantation in patients with a mechanical mitral valve,
      with 94% using heparin to provide preoperative anticoagulation: 58%
      unfractionated heparin, 40% low molecular weight heparin. The maximum accepted
      international normalized ratio for implantation ranged from 1.4 to 3 (median
      1.8). Postoperatively, 86% restart heparin after a mean 8.5 hours. Only 11%
      continue oral anticoagulation throughout the implantation period. There is a
      hierarchy of perceived embolic risk with doctors using progressively less
      anticoagulation in patients with prosthetic aortic valve, high-risk, and low-risk
      atrial fibrillation. In contrast, only 7% of implanters stop theinopyridines
      prior to device implantation in patients with a 2-month-old drug eluting stent.
      CONCLUSION: Perioperative anticoagulation management of patients undergoing
      device procedures is currently performed with little consensus. This emphasizes
      the need for careful national and international audit of periprocedural
      anticoagulation management and its associated complications with a view to
      developing international consensus guidelines. (PACE 2010; 389-393).

PMID- 20132501
TI  - Ablation of post-myocardial infarction focal ventricular tachycardia.
AB  - In the chronic phase of myocardial infarction, the presence of scar areas allows
      the development of macro-reentries which become the most frequent mechanism
      underlying ventricular tachycardia (VT). A focal mechanism has been already
      described in the presence of scar in animal models or in humans but only during
      surgery. We report a case of focal automatic VT arising from postinfarction scar
      fibrosis, successfully mapped and ablated during an electro-physiological
      procedure.

PMID- 20132502
TI  - Beta-blocker in post-myocardial infarct survivors with preserved left ventricular
      systolic function.
AB  - BACKGROUND: Long-term beta-blockade therapy is beneficial in post-myocardial
      infarct (MI) patients with left ventricular (LV) dysfunction; nevertheless, its
      benefit in post-MI patients with preserved LV function remains unclear. The
      objective of this study is to investigate the effects of long-term beta-blockade
      therapy on the clinical outcomes in post-MI patients with preserved LV function.
      HYPOTHESIS: The beneficial effects of long-term beta-blockade therapy in post-MI
      patients with impaired LV function may extend to those with preserved LV
      function. METHODS: Of 617 consecutive post-MI patients referred for cardiac
      rehabilitation program, 208 patients (age: 62.7 +/- 0.8 years; male: 76%) with
      preserved LV function (ejection fraction >or= 50%), negative exercise stress
      test, and on angiotensin-converting enzyme inhibition were studied. RESULTS:
      Baseline characteristics were comparable between patients on beta-blocker (n =
      154) and not on beta-blocker (n = 54). After a mean follow-up of 58.5 +/- 2.7
      months, 14 patients not on beta-blocker (26%) and 14 patients on beta-blocker
      (9%) died with hazard ratio (HR) of 2.5 (95% confidence interval [CI]: 1.25-6.42,
      P = 0.01). Likewise, patients not on beta-blocker had a higher incidence of
      cardiac death (HR: 3.0, 95% CI: 1.07-12.10, P = 0.04), and non-sudden cardiac
      death (HR: 10.1, 95% CI: 1.82-89.65, P = 0.01), but not sudden cardiac death
      compared with patients on beta-blocker (HR: 1.6, 95% CI: 0.34-7.61, P = 0.54). A
      Cox regression analysis revealed that only advanced age (>or=75 years; HR: 2.55,
      95% CI: 1.18-5.49, P = 0.02) and the absence of beta-blocker (HR: 2.41, 95% CI:
      1.14-5.09, P = 0.02) were independent predictors for mortality. CONCLUSION: beta
      blocker use was associated with a decrease in overall mortality and cardiac death
      in post-MI patients with preserved LV function.

PMID- 20132503
TI  - Predictive capability of left atrial size measured by CT, TEE, and TTE for
      recurrence of atrial fibrillation following radiofrequency catheter ablation.
AB  - BACKGROUND: Recurrence of atrial fibrillation (AF) after radiofrequency catheter
      ablation (RFCA) has been well established and is in part related to left atrial
      (LA) size. The purpose of this study was to assess the predictive capability of
      LA diameter (LAD) and LA volume (LAV) by echocardiography and computed tomography
      (CT) to determine success in patients undergoing RFCA of AF. METHODS: Eighty
      eight patients with paroxysmal or persistent AF who had undergone RFCA and had a
      prior transthoracic echocardiogram (TTE), transesophageal echocardiogram (TEE),
      and CT were enrolled in the study. TTE LADs and LV ejection fraction as well as
      TEE LADs and LAVs in three views were recorded. CT LAVs were also recorded.
      Clinical parameters prior to ablation as well as at 1-year follow-up were
      assessed. RESULTS: A total of 40 (45%) patients with paroxysmal AF and 48 (55%)
      patients with persistent AF were analyzed. Paroxysmal AF patients had a RFCA
      success rate of 88% at 1 year with persistent AF patients having a 52% success
      rate (P < 0.001). A CT-derived LAV >or= 117 cc was associated with an odds ratio
      (OR) for recurrence of 4.8 (95% confidence interval [CI]=[1.4-16.4], P = 0.01)
      while a LAV >or=130 cc was associated with an OR for recurrence of 22.0 (95% CI
      =[2.5-191.0], P = 0.005) after adjustment for persistent AF. CONCLUSIONS: LA
      dimensions and AF type are highly predictive of AF recurrence following RFCA. LAV
      by CT has significant predictive benefit over standard LADs in severely enlarged
      atria even after adjustment for AF type.

PMID- 20132504
TI  - A survey of the practice of lead extraction in the United States.
AB  - BACKGROUND: Endovascular lead extraction is an important component of the
      management of patients with chronically implanted arrhythmia control devices.
      Although it is associated with the potential for significant morbidity and
      mortality, there is little information about its scope and practice. METHODS: We
      surveyed 1,000 physician members of the Heart Rhythm Society via e-mail
      solicitation. RESULTS: Of the 252 respondents (25%), 221 (88%) reported either
      performing extractions themselves (63%), or having privileges at a hospital where
      extractions are performed (25%). Electrophysiologists perform extractions at most
      sites (83%) but cardiac surgeons perform endovascular lead extraction at a
      significant minority of sites (20%). Most respondents report low annual volumes
      of extractions at their site: 15% reported <10 procedures/year, 42% 10-25
      procedures/year, 23% 26-50 procedure/year, and only 19% reported >50
      procedures/year. Thirty-six percent of respondents reported that extractions were
      done in the operating room (OR) with surgeon present or immediately available,
      39% in the electrophysiology (EP) lab with surgeon and OR identified and
      available, and 25% in EP lab without a surgeon or OR identified. The overall
      risks of lead extraction were felt to be 1-5% of major complication and 0.5-1% of
      mortality, roughly in line with published data. CONCLUSIONS: While there is
      agreement as to the risk of major complication and death from lead extraction,
      the degree of surgical availability varies considerably. The new guidelines
      document recommends the ability to promptly initiate an emergent surgical
      procedure, and this should be an important goal for all extractionists.

PMID- 20132505
TI  - Management and clinical outcomes of acute cardiac tamponade complicating
      electrophysiologic procedures: a single-center case series.
AB  - BACKGROUND: Cardiac perforation with tamponade is an infrequent occurrence during
      an electrophysiologic procedure. The customary approach to management includes
      volume resuscitation followed by pericardiocentesis. Such a procedure, however,
      is not without its own risk, especially when performed emergently. We
      hypothesized that some patients experiencing this type of complication can be
      managed successfully in a conservative fashion, without the need for an
      additional invasive procedure. METHODS: We retrospectively analyzed the clinical
      outcomes and echocardiographic features of 33 consecutive patients who
      experienced this complication during cardiac electrophysiology (EP) procedures
      performed at our institution from 1988 to 2007. Nineteen patients (58%) were
      managed conservatively with intravenous fluids and vasopressors (Group A).
      Fourteen patients (42%) were managed invasively with pericardiocentesis (Group
      B). RESULTS: The mean systolic blood pressure at diagnosis did not differ between
      the two groups (64 vs 71 mmHg, P = 0.134). The mean lengths of hospitalization
      (4.7 vs 4.9 days, P = 0.75) and survival to hospital discharge (100% in both
      groups) were also similar. A large pericardial effusion (>or=2 cm) was seen
      predominantly among Group B patients. There was a statistically significant
      temporal trend toward managing this type of complication invasively (P = 0.038).
      CONCLUSION: Among patients who experience cardiac perforation as an acute
      complication of EP procedure, there appears to be a role for conservative
      management in a subset of patients who do not have echocardiographic evidence of
      a large effusion and who respond well to initial stabilizing measures consisting
      of fluids and vasopressors.

PMID- 20132506
TI  - The feasibility of fully automated pacemaker advise in treating atrial
      tachyarrhythmias.
AB  - BACKGROUND: Modern pacemakers continuously store significant cardiac-related
      events. Interpreting these data and reprogramming the pacemaker can be time
      consuming and demands expert knowledge. A software-based expert system, the
      therapy advisor (TA), was developed, which analyzes stored data and provides
      reprogramming recommendations. This study addresses whether pacemaker experts
      consider the messages that are automatically generated appropriate in the
      management of atrial tachyarrhythmias/atrial fibrillation (AT/AF). METHODS: This
      observational, international, multicenter study follows 150 patients with
      suspected or documented atrial arrhythmias who received a dual-chamber pacemaker
      (model Vitatron T-70, Medtronic Inc., Minneapolis, MN, USA) incorporating the TA.
      The TA summarizes technical and clinical data stored in the pacemaker into key
      messages and may suggest programming changes. Twenty-five cardiologists examined
      their patients per normal practice during two follow-up visits. They reported the
      therapy changes they deemed necessary without initially reviewing the TA
      messages. Next, they rated their satisfaction with and the clinical relevance of
      the TA messages and recorded the final therapy changes. RESULTS: The TA generated
      (mostly AT/AF-related) main observations in 49% and programming advice in 33% of
      the patients. The experts rated 95% of the TA messages as satisfactory and deemed
      therapy changes necessary in roughly half the patients. Pacemaker changes in
      AT/AF therapy or general settings were prompted primarily by the diagnostic
      information stored in the device. Medication changes were mostly led by the
      symptoms reported by the patient. CONCLUSION: This study demonstrates that
      experienced cardiologists agree with 95% of the observations and programming
      suggestions that the TA automatically generates.

PMID- 20132507
TI  - Changing QRS morphology during accessory pathway ablation.

PMID- 20132508
TI  - Narrow QRS complex tachycardia inducing Wide QRS complex tachycardia: what is the
      mechanism?

PMID- 20132509
TI  - All is not lost: utilizing continuous remote ILR monitoring to diagnose syncope.
AB  - A 63-year-old man with frequent unexplained syncope was implanted with a second
      generation remotely monitored implantable loop recorder for continuous
      electrocardiogram (ECG) monitoring. He had a subsequent syncopal episode and
      despite accidental destruction of his patient activator, vital ECG data from the
      event were transmitted wirelessly, enabling a cardiac arrhythmia to be excluded.
      This case highlights the benefit of remote monitoring in syncope assessment, as
      well as a transmission system that ensures prompt analysis of the ECG data and
      therefore rapid optimal patient management.

PMID- 20132511
TI  - Retraction: ANTI-HIV-1 activities of photodynamic therapy using hematoporphyrin
      monomethyl ether.

PMID- 20132510
TI  - Low-light-induced violaxanthin de-epoxidation in shortly preheated leaves:
      uncoupling from Delta pH-dependent nonphotochemical quenching.
AB  - Plants protect themselves against excessive light by the induction of Delta pH
      dependent nonphotochemical quenching (qE) that is associated with de-epoxidation
      of violaxanthin (V) to zeaxanthin (Z) in thylakoid membranes. In this work, we
      report that low light (12 micromol photons m(-2) s(-1)) is sufficient for a
      marked stimulation of the V to Z conversion in shortly preheated wheat leaves (5
      min, 40 degrees C), but without a substantial increase in qE. Re-irradiation of
      these leaves with high light led to a rapid induction of nonphotochemical
      quenching, implying a potential photoprotective role of low-light-induced Z in
      preheated leaves. On the contrary to low light conditions, preheated leaves
      exposed to high light behaved similar to nonheated leaves with respect to the V
      to Z conversion and qE induction. The obtained results indicate that low-light
      induced lumen acidification in preheated leaves is high enough to activate V de
      epoxidation, but not sufficiently high to induce the formation of quenching
      centers.

PMID- 20132512
TI  - Dependence of photochemical reactivity of the all-trans retinal protonated Schiff
      base on the solvent and the excitation wavelength.
AB  - An all-optical experimental technique aimed at measuring photoisomerization
      quantum yield (phi) of the all-trans protonated Schiff base of retinal in
      solution has been implemented. Upon the increase in the excitation wavelength
      from 400 to 540 nm a slight increase in phi from 0.16 +/- 0.03 to 0.20 +/- 0.02
      is observed in the chromophore dissolved in methanol, whereas the phi value of
      the one dissolved in acetonitrile varies only from 0.22 +/- 0.03 (400 nm) to 0.23
      +/- 0.04 (540 nm). The results suggest that dissipation of the excited-state
      vibrational energy excess, along with environment-induced modifications of the
      potential energy surfaces are necessary for an efficient retinal
      photoisomerization in both solvent and protein environment.

PMID- 20132513
TI  - Cellular uptake and photodynamic activity of protein nanocages containing
      methylene blue photosensitizing drug.
AB  - This study reports that photosensitizers encapsulated in supramolecular protein
      cages can be internalized by tumor cells and can deliver singlet oxygen
      intracellularly for photodynamic therapy (PDT). As an alternative to other
      polymeric and/or inorganic nanocarriers and nanoconjugates, which may also
      deliver photosensitizers to the inside of the target cells, protein nanocages
      provide a unique vehicle of biological origin for the intracellular delivery of
      photosensitizing molecules for PDT by protecting the photosensitizers from
      reactive biomolecules in the cell membranes, and yet providing a coherent,
      critical mass of destructive power (by way of singlet oxygen) upon specific light
      irradiation for photodynamic therapy of tumor cells. As a model, we demonstrated
      the successful encapsulation of methylene blue (MB) in apoferritin via a
      dissociation-reassembly process controlled by pH. The resulting MB-containing
      apoferritin nanocages show a positive effect on singlet oxygen production, and
      cytotoxic effects on MCF-7 human breast adenocarcinoma cells when irradiated at
      the appropriate wavelength (i.e. 633 nm).

PMID- 20132514
TI  - Effect of UVA or UVB irradiation on cutaneous lipids in films or in solution.
AB  - The barrier function of the skin is largely due to the stratum corneum which is
      essentially composed of lipids. Different external factors, such as UV
      irradiation, affect this skin layer and are responsible for a destabilization of
      the supramolecular organization of its constituted lipids. In this work, mass
      spectrometry and infrared spectroscopy are combined to study the correlation
      between the formation of oxidative compounds by UV irradiation and the lipid
      organization. Experiments were carried out on unsaturated lipids in film or
      solution form, exposed to UVA or UVB irradiation. UV exposure leads to the
      formation of oxygenated entities in the case of lipids with an unsaturated fatty
      acid moiety, resulting in a decrease in their packing which is greater when the
      lipids are in solution. The packing decrease is even greater following UVB
      irradiation.

PMID- 20132515
TI  - Production of antibodies in plants: status after twenty years.
AB  - Thanks to their potential to bind virtually all types of molecules; monoclonal
      antibodies are in increasing demand as therapeutics and diagnostics. To overcome
      the overloading of current production facilities, alternative expression systems
      have been developed, of which plants appear the most promising. In this review,
      we focus on the expression of monoclonal IgG or IgM in plant species. We analyse
      the data for 32 different antibodies expressed in various ways, differing in DNA
      construction, transformation method, signal peptide source, presence or absence
      of an endoplasmic reticulum retention sequence, host species and the organs
      tested, together resulting in 98 reported combinations. A large heterogeneity is
      found in the quantity and quality of the antibody produced. We discuss in more
      detail the strategy used to express both chains, the nature of the transcription
      promoters, subcellular localization and unintended proteolysis, when encountered.

PMID- 20132516
TI  - Modelling pollen-mediated gene flow in rice: risk assessment and management of
      transgene escape.
AB  - Fast development and commercialization of genetically modified plants have
      aroused concerns of transgene escape and its environmental consequences. A model
      that can effectively predict pollen-mediated gene flow (PMGF) is essential for
      assessing and managing risks from transgene escape. A pollen-trap method was used
      to measure the wind-borne pollen dispersal in cultivated rice and common wild
      rice, and effects of relative humidity, temperature and wind speed on pollen
      dispersal were estimated. A PMGF model was constructed based on the pollen
      dispersal pattern in rice, taking outcrossing rates of recipients and cross
      compatibility between rice and its wild relatives into consideration. Published
      rice gene flow data were used to validate the model. Pollen density decreased in
      a simple exponential pattern with distances to the rice field. High relative
      humidity reduced pollen dispersal distances. Model simulation showed an increased
      PMGF frequency with the increase of pollen source size (the area of a rice
      field), but this effect levelled off with a large pollen-source size. Cross
      compatibility is essential when modelling PMGF from rice to its wild relatives.
      The model fits the data well, including PMGF from rice to its wild relatives.
      Therefore, it can be used to predict PMGF in rice under diverse conditions (e.g.
      different outcrossing rates and cross-compatibilities), facilitating the
      determination of isolation distances to minimize transgene escape. The PMGF model
      may be extended to other wind-pollinated plant species such as wheat and barley.

PMID- 20132517
TI  - Comparison of two GM maize varieties with a near-isogenic non-GM variety using
      transcriptomics, proteomics and metabolomics.
AB  - The aim of this study was to evaluate the use of four nontargeted analytical
      methodologies in the detection of unintended effects that could be derived during
      genetic manipulation of crops. Three profiling technologies were used to compare
      the transcriptome, proteome and metabolome of two transgenic maize lines with the
      respective control line. By comparing the profiles of the two transgenic lines
      grown in the same location over three growing seasons, we could determine the
      extent of environmental variation, while the comparison with the control maize
      line allowed the investigation of effects caused by a difference in genotype. The
      effect of growing conditions as an additional environmental effect was also
      evaluated by comparing the Bt-maize line with the control line from plants grown
      in three different locations in one growing season. The environment was shown to
      play an important effect in the protein, gene expression and metabolite levels of
      the maize samples tested where 5 proteins, 65 genes and 15 metabolites were found
      to be differentially expressed. A distinct separation between the three growing
      seasons was also found for all the samples grown in one location. Together, these
      environmental factors caused more variation in the different
      transcript/protein/metabolite profiles than the different genotypes.

PMID- 20132518
TI  - Regulation by light of ammonium transport systems in Chlamydomonas reinhardtii.
AB  - The unicellular green alga Chlamydomonas reinhardtii is able to take up
      methylammonium/ammonium from the medium at different stages of its sexual life
      cycle. Vegetative cells and pre-gametes mostly used a low-affinity system (LATS)
      component, but gametes obtained after light treatment of N-deprived pre-gametes
      expressed both LATS and high-affinity system (HATS) components for the uptake of
      methylammonium/ammonium. The activity of the LATS component was stimulated by
      light in only 5 min in a process independent of protein synthesis. By using the
      lrg6 mutant that produces sexually competent gametes in the dark, light effects
      on ammonium transport and gamete differentiation have been separately analysed.
      We have found light regulation of four Amt1 genes: Amt1; 1, Amt1; 2, Amt1; 4 and
      Amt1; 5. Whereas light-dependent expression of Amt1; 1, Amt1; 2 and Amt1; 4 was
      independent of gametogenesis, and that of Amt1; 5 was activated in the lrg6
      mutant, suggesting a connection between this transporter and the subsequent
      events taking place during gametogenesis.

PMID- 20132519
TI  - Ligands of boron in Pisum sativum nodules are involved in regulation of oxygen
      concentration and rhizobial infection.
AB  - Boron (B) is an essential nutrient for N(2)-fixing legume-rhizobia symbioses, and
      the capacity of borate ions to bind and stabilize biomolecules is the basis of
      any B function. We used a borate-binding-specific resin and immunostaining
      techniques to identify B ligands important for the development of Pisum sativum
      Rhizobium leguminosarum 3841 symbiotic nodules. arabinogalactan-extensin (AGPE),
      recognized by MAC 265 antibody, appeared heavily bound to the resin in extracts
      derived from B-sufficient, but not from B-deficient nodules. MAC 265 stained the
      infection threads and the extracellular matrix of cortical cells involved in the
      oxygen diffusion barrier. In B-deprived nodules, immunolocalization of MAC 265
      antigens was significantly reduced. Leghaemoglobin (Lb) concentration largely
      decreased in B-deficient nodules. The absence of MAC 203 antigens in B-deficient
      nodules suggests a high internal oxygen concentration, as this antibody detects
      an epitope on the lipopolysaccharide (LPS) of bacteroids typically expressed in
      micro-aerobically grown R. leguminosarum 3841. However, B-deprived nodules did
      not accumulate oxidized lipids and proteins, and revealed a decrease in the
      activity of the major antioxidant enzyme ascorbate peroxidase (APX). Therefore, B
      deficiency reduced the stability of nodule macromolecules important for rhizobial
      infection, and for regulation of oxygen concentration, resulting in non
      functional nodules, but did not appear to induce oxidative damage in low-B
      nodules.

PMID- 20132520
TI  - Disruption of Nap14, a plastid-localized non-intrinsic ABC protein in Arabidopsis
      thaliana results in the over-accumulation of transition metals and in aberrant
      chloroplast structures.
AB  - Chloroplasts are the major sink for Fe in shoot tissues because of the
      requirements of the photosynthetic process and to storage in ferritins. Such
      requirements are common both to plastids and to their evolutionary progenitors,
      the cyanobacteria. Here, we examined whether iron transport mechanisms were
      conserved throughout the evolution of photosynthetic organisms. Comparison of the
      sequences of putative plastid transporters from Arabidopsis thaliana with those
      involved in cyanobacterial Fe transport identified two orthologs of the FutC
      protein, AtNAP11 and AtNAP14. To study their function, we analysed insertional
      mutants in the genes coding for these proteins. Both nap11/nap11 and nap14/nap14
      plants exhibited severe growth defects. Significant changes in transition metal
      homeostasis were detected only in nap14/nap14. This mutant was found to contain
      approximately 18 times more Fe in the shoot tissue than in wild-type plants. The
      increased shoot transition metal content was accompanied by a specific loss of
      chloroplast structures and by a reduction in transcript levels of Fe homeostasis
      related genes. Based on these results, we propose that AtNAP14 plays an important
      role in plastid transition metal homeostasis. One possibility is that AtNAP14 is
      part of a chloroplast transporter complex. Alternatively, AtNAP14 function may be
      in regulating transition metal homeostasis.

PMID- 20132521
TI  - Differential gene expression in senescing leaves of two silver birch genotypes in
      response to elevated CO2 and tropospheric ozone.
AB  - Long-term effects of elevated CO(2) and O(3) concentrations on gene expression in
      silver birch (Betula pendula Roth) leaves were studied during the end of the
      growing season. Two birch genotypes, clones 4 and 80, with different ozone growth
      responses, were exposed to 2x ambient CO(2) and/or O(3) in open-top chambers
      (OTCs). Microarray analyses were performed after 2 years of exposure, and the
      transcriptional profiles were compared to key physiological characteristics
      during leaf senescence. There were genotypic differences in the responses to
      CO(2) and O(3). Clone 80 exhibited greater transcriptional response and capacity
      to alter metabolism, resulting in better stress tolerance. The gene expression
      patterns of birch leaves indicated contrasting responses of senescence-related
      genes to elevated CO(2) and O(3). Elevated CO(2) delayed leaf senescence and
      reduced associated transcriptional changes, whereas elevated O(3) advanced leaf
      senescence because of increased oxidative stress. The combined treatment
      demonstrated that elevated CO(2) only temporarily alleviated the negative effects
      of O(3). Gene expression data alone were insufficient to explain the O(3)
      response in birch, and additional physiological and biochemical data were
      required to understand the true O(3) sensitivity of these clones.

PMID- 20132522
TI  - Micro-particle-induced X-ray emission mapping of elemental distribution in roots
      of a Mediterranean-type sclerophyll, Agathosma betulina (Berg.) Pillans,
      colonized by Cryptococcus laurentii.
AB  - The role of rhizosphere yeasts as plant nutrient-scavenging microsymbionts in
      resource-limited Mediterranean-type heathlands is unknown. This study, therefore,
      focused on quantitative elemental distribution within the roots of a medicinal
      sclerophyll, Agathosma betulina (Berg.) Pillans, grown under nutrient-poor
      conditions, and colonized by Cryptococcus laurentii. Micro-particle-induced X-ray
      emission (PIXE) was used to assess quantitative elemental distribution within the
      roots of A. betulina inoculated with viable C. laurentii, as well as within roots
      of control plants that received autoclaved yeast. To aid in the interpretation of
      heterogeneous elemental distribution patterns, apoplastic barriers (Casparian
      bands) in root tissues were located using fluorescence microscopy. In addition,
      root cross-sections were examined for endophytic C. laurentii using light and
      transmission electron microscopy (TEM). The average concentrations of P, Fe and
      Mn were significantly (P < 0.05) higher in roots of yeast-inoculated plants,
      compared to control plants. Casparian bands were observed in the exodermal cells
      of both treatments, and the presence of these bands was correlated with elemental
      enrichment in the epi/exodermal-outer cortical tissues. Light and TEM micrographs
      revealed that the yeast was not a root endophyte. This is the first report
      describing the role of a soil yeast as a plant nutrient-scavenging microsymbiont.

PMID- 20132523
TI  - Factors associated with postpartum depression and abusive behavior in mothers
      with infants.
AB  - AIMS: This study was conducted to examine factors associated with postpartum
      depression and abusive behavior in mothers with infants. METHODS: Data were
      collected from baby check-ups in Japan and 413 participants were included in an
      analysis using: (i) an Original Questionnaire; (ii) the Zung Self-rating
      Depression Scale (ZSDS); (iii) the Parental Bonding Instrument; and (iv) the
      Childcare Anxiety Scale (CAS). Covariance structural analyses were performed to
      examine interconnections among the Parental Bonding Instrument subscales, CAS
      subscales ('worry about parenting', 'burden of nursing time', 'difficulty of
      bonding'), ZSDS, 'fear of being abusive', and 'abusive behavior'. RESULTS: Of the
      413 mothers, 14.5% showed higher than moderate levels of depression (ZSDS > or =
      50). In covariance structural analyses, 'depression' was strongly influenced by
      'worry about parenting' in all variances, but was not associated with 'abusive
      behavior'. 'Worry about parenting' also had a strong influence on 'fear of being
      abusive', but did not affect 'abusive behavior'. Low 'maternal care' had most
      influence on 'difficulty of bonding', and 'difficulty of bonding' only affected
      'abusive behavior'. CONCLUSIONS: The outcome of this study suggests that
      excessive worrying related to postpartum depression, 'fear of being abusive', and
      bonding difficulty are primary predictors of child abuse. Postpartum depression
      was not a predictor for abusive behavior after exclusion of the impact of bonding
      difficulties on abusive behavior. Therefore, the correlation between postpartum
      depression and abusive behavior identified in previous reports may have been
      influenced by bonding difficulties.

PMID- 20132524
TI  - Attitudes of early-career psychiatrists in Japan toward child and adolescent
      psychiatry and their career decision.
AB  - The aim of the present study was to carry out a national survey to understand the
      attitude of early-career psychiatrists toward child and adolescent psychiatry
      (CAP). The subjects were 348 early-career psychiatrists. A questionnaire was sent
      to the subjects and returned anonymously. A total of 234 subjects (67.2%)
      responded. Ten out of 115 psychiatrists (8.9%) in their first-third year of
      experience, and 18 of 119 psychiatrists (15.1%) in their fourth-10th year
      answered that they had interest in CAP. Psychiatry rotations with adequate CAP
      cases may be necessary to attract early-career psychiatrists to CAP.

PMID- 20132525
TI  - No association between polymorphism in tyrosine hydroxylase and personality
      traits in healthy Japanese subjects.
AB  - The aim of the present study was to investigate whether there is an association
      between the (TCAT)(n) repeat polymorphism in the tyrosine hydroxylase (TH) gene
      and personality. The (TCAT)(n) repeat polymorphism in the TH gene was genotyped
      in 898 healthy Japanese subjects. Personality traits were evaluated using the
      Temperament and Character Inventory (TCI). There was no significant difference in
      the TCI scores of subjects with and without the T9 allele. Furthermore, no
      significant association was found between each genotype and the TCI scores, even
      when the TCI scores were compared with the homozygous genotype. These findings
      suggest that the (TCAT)(n) repeat polymorphism in the TH gene does not contribute
      to the personality traits evaluated on the TCI in healthy Japanese subjects.

PMID- 20132526
TI  - Clinical efficacy of individual cognitive behavior therapy for
      psychophysiological insomnia in 20 outpatients.
AB  - AIM: Twenty patients (14 of them women) suffering from psychophysiological
      insomnia (PPI) were enrolled for cognitive behavior therapy (CBT). The mean age
      of the patients was 56.9 years, and the mean duration of insomnia morbidity was
      8.9 years. Each received individual combined CBT treatments consisting of
      stimulus control, sleep reduction, cognitive therapy and sleep hygiene education
      over a period of 1 month. METHODS: Just before the CBT and after its completion,
      sleep measurements were conducted that involved (i) sleep logs, Dysfunctional
      Beliefs and Attitudes about Sleep Scale (DBAS), and the Pittsburgh Sleep Quality
      Index (PSQI); (ii) actigraphy measurement; (iii) dissociation between subjective
      and objective evaluation of sleep calculated from sleep logs and actigraphy
      results; and (iv) correlation between DBAS and the aforementioned sleep
      parameters. Because the intention was to focus on patients' incorrect cognition
      about sleep, the definition 'changes in dissociation between the sleep log and
      actigraphically measured sleep' was used as the primary outcome and 'changes in
      DBAS score' as the secondary outcome. RESULTS: After the CBT the following was
      found: (i) underestimation by PPI patients of the objective evaluation of sleep;
      (ii) a decrease in the dissociation between the subjective and objective
      evaluation of sleep; (iii) improvement of the DBAS; and (iv) improvement of sleep
      logs and actigraphy measurements. Moreover, there was a correlation between the
      improvement of PSQI, sleep logs and DBAS. CONCLUSION: CBT for insomnia is able to
      redress incorrect cognition about sleep, leading to improvement of the disorder.

PMID- 20132527
TI  - Regional cerebral blood flow changes in female to male gender identity disorder.
AB  - AIMS: Despite a range of research on gender identity disorder (GID), at present
      there is no scientific consensus on whether the etiology of GID is mental or
      physical. In particular recent advances in the technology of neuroimaging
      research have led to an increased understanding of the biological basis of
      various mental disorders. GID also should be evaluated from this perspective. The
      aim of the present study was therefore to do the first trial to examine the
      regional cerebral blood flow (rCBF) in GID. METHODS: Persons considered
      biologically male fulfilling the GID criteria are termed male to female (MTF)
      and, conversely, persons considered biological female are termed female to male
      (FTM). We compared 11 FTM subjects and nine age- and handedness-matched female
      control subjects. None of the subjects was regularly taking medication and none
      had any kind of physical or psychiatric comorbidity. To evaluate rCBF in GID
      subjects and control subjects, statistical parametric mapping analysis of (99m)Tc
      ethyl-cysteinate dimer single-photon emission computed tomography was used.
      RESULTS: GID subjects had a significant decrease in rCBF in the left anterior
      cingulate cortex (ACC) and a significant increase in the right insula compared to
      control subjects. CONCLUSIONS: The ACC and insula are regions that have been
      noted as being related to human sexual behavior and consciousness. From these
      findings, useful insights into the biological basis of GID were suggested.

PMID- 20132528
TI  - Predictors of antidepressant adherence: results of a Japanese Internet-based
      survey.
AB  - AIM: The purpose of the present study was to identify the
      psychosocial/pharmacological predictors of antidepressant (AD) adherence.
      METHODS: An Internet-based survey was conducted among 1151 Japanese individuals
      with major depressive disorder. Subjects were asked to report their degree of non
      adherence for each AD taken using a 5-point Likert scale: 0, never forget; 1,
      rarely forget; 2, occasionally forget; 3, sometimes forget; and 4, often forget.
      The highest number reported among each subject was assigned as their low
      adherence index (LAI). Individuals with an LAI > or = 3 were defined as members
      of the low adherence (LA) group. Predictors of LA was analyzed using bivariate
      and multivariate models, both among the total number of subjects and single AD
      subgroup (n = 657). RESULTS: Nearly one-third of subjects (n = 381, 33.1%)
      reported LA. On bivariate analysis, LA was associated with lower age, worker or
      student status (vs unemployed or housewife), higher daily dosing frequency (DDF),
      low drug satisfaction, and a neutral/negative doctor-patient relationship (DPR; P
      < 0.001). In a multivariate model, LA was predicted by age (< or =34 years: odds
      ratio [OR], 1.64), worker or student status (OR, 1.87), higher DDF (> or =twice
      daily: OR, 1.61), and neutral/negative DPR (OR, 1.54; P < 0.01). Among the single
      AD subgroup, adherence was similar between those on selective serotonin reuptake
      inhibitors/serotonin-noradrenaline reuptake inhibitors and tricyclics. Use of
      neither medication was associated with adherence in a multivariate model.
      CONCLUSION: LA was predicted by lower age, worker or student status, higher DDF,
      and neutral/negative DPR. Adherence was not significantly different between
      subjects on newer agents and tricyclics.

PMID- 20132529
TI  - Randomized, single-blind, trial of sertraline and buspirone for treatment of
      elderly patients with generalized anxiety disorder.
AB  - AIM: Generalized anxiety disorder (GAD) in elderly people is common, but few
      systematic studies regarding the best treatments have been performed. The aim of
      the present study was to evaluate the efficacy and safety of sertraline and
      buspirone in the treatment of elderly patients with GAD. METHODS: Based on
      selection criteria, 46 patients were recruited who met DSM-IV criteria for GAD.
      Patients were randomly assigned to sertraline (50-100 mg/day) or buspirone (10-15
      mg/day) for 8 weeks in a single-blind trial. The primary outcome measure used in
      the present study was the Hamilton Rating Scale for Anxiety (HRSA). RESULTS: Both
      sertraline and buspirone had significant anxiolytic efficacy. A steady decrease
      in the total HRSA scores for both groups was observed throughout the study
      period. After 2 and 4 weeks, buspirone was found to be significantly superior to
      sertraline (P < 0.001), but at the end of study period this difference did not
      reach statistical significance (P = 0.16). The mean HRSA score after 8 weeks
      significantly decreased in subjects treated with sertraline (P < 0.001), and
      buspirone (P < 0.001). No clinically adverse events or changes in laboratory test
      results were observed during the study period. CONCLUSION: Both sertraline and
      buspirone appear to be efficacious and well tolerated in the treatment of GAD in
      elderly patients. Further studies with larger sample size, evaluating the effect
      of medical illness, cognitive impairment, depression, and combined therapy with
      support and psychotherapy are needed.

PMID- 20132530
TI  - Clinical utility of the Chinese version of the Pediatric Daytime Sleepiness Scale
      in children with obstructive sleep apnea syndrome and narcolepsy.
AB  - AIM: The present study examined the psychometric properties of the Chinese
      version of the Pediatric Daytime Sleepiness Scale (PDSS) and the utility of the
      PDSS as a screening tool for pathological daytime sleepiness in teenagers with
      obstructive sleep apnea (OSA) and narcolepsy. METHODS: The PDSS was first
      administered to 238 middle and high school students to assess the reliability of
      the scale, and then administered to 28 teenagers with OSA, 31 teenagers with
      narcolepsy, and 34 normal controls to evaluate its clinical utility. RESULTS:
      Test-retest reliability and internal consistency were acceptable. The PDSS scores
      were significantly higher in narcoleptic subjects than in subjects with OSA, and
      higher in OSA syndrome (OSAS) subjects than normal controls. Furthermore, the
      scores decreased in narcoleptic subjects after medical treatment. Both
      reliability and validity were proven to be good. As a screening tool for
      narcolepsy, receiver operator characteristic (ROC) curve analysis showed that the
      PDSS, with a cut-off score of 16/17, had good sensitivity (87.1%) and fair
      specificity (74.3%) for identifying individuals with narcolepsy. When used for
      screening OSA, however, the differentiating power was not as good. CONCLUSION:
      The PDSS is a reliable and valid tool for the measurement of sleepiness in
      clinical youth populations. When used as a screening tool, it is useful for sleep
      disorders involving more severe pathological sleepiness, as in narcolepsy.

PMID- 20132531
TI  - Relationship of alexithymia and temperament and character dimensions with
      lifetime post-traumatic stress disorder in male alcohol-dependent inpatients.
AB  - AIMS: The purpose of the present study was to evaluate the prevalence of lifetime
      post-traumatic stress disorder (PTSD) in male alcohol-dependent inpatients and to
      investigate the relationship of PTSD with alexithymia and temperament and
      character dimensions. METHODS: Participants were 156 consecutively admitted male
      alcohol-dependent subjects. Patients were investigated using the Clinician
      Administered PTSD Scale (CAPS), the Toronto Alexithymia Scale (TAS-20) and the
      Temperament and Character Inventory (TCI). RESULTS: Among alcohol-dependent
      inpatients 32.1% were considered as having lifetime PTSD. Mean scores of
      alexithymia, novelty seeking (NS), harm avoidance (HA) and self-transcendence
      (ST) were higher in the PTSD group, whereas age and self-directedness (S) were
      lower. Among age and other factors of TAS-20, 'difficulty in identifying feelings
      (DIF)' predicted PTSD in a logistic regression model. When age and personality
      dimensions of TCI were taken as independent variables, S predicted PTSD in the
      logistic regression model. Finally, among subscales of TCI, 'impulsiveness versus
      reflection' (NS2) and 'congruent second nature versus bad habits' (S5) predicted
      PTSD. CONCLUSIONS: Alexithymia and personality traits, particularly high DIF and
      S scores are related with lifetime PTSD diagnosis, even when controlling for age
      among alcohol-dependent inpatients. Causal relationships between alexithymia,
      personality dimensions and PTSD, and their implications on treatment are not
      clear and should be evaluated in longitudinal studies.

PMID- 20132532
TI  - Highly conserved motifs in non-coding regions of Sirevirus retrotransposons: the
      key for their pattern of distribution within and across plants?
AB  - BACKGROUND: Retrotransposons are key players in the evolution of eukaryotic
      genomes. Moreover, it is now known that some retrotransposon classes, like the
      abundant and plant-specific Sireviruses, have intriguingly distinctive host
      preferences. Yet, it is largely unknown if this bias is supported by different
      genome structures. RESULTS: We performed sensitive comparative analysis of the
      genomes of a large set of Ty1/copia retrotransposons. We discovered that
      Sireviruses are unique among Pseudoviridae in that they constitute an ancient
      genus characterized by vastly divergent members, which however contain highly
      conserved motifs in key non-coding regions: multiple polypurine tract (PPT)
      copies cluster upstream of the 3' long terminal repeat (3'LTR), of which the
      terminal PPT tethers to a distinctive attachment site and is flanked by a
      precisely positioned inverted repeat. Their LTRs possess a novel type of repeated
      motif (RM) defined by its exceptionally high copy number, symmetry and core CGG
      CCG signature. These RM boxes form CpG islands and lie a short distance upstream
      of a conserved promoter region thus hinting towards regulatory functions.
      Intriguingly, in the envelope-containing Sireviruses additional boxes cluster at
      the 5' vicinity of the envelope. The 5'LTR/internal domain junction and a polyC
      rich integrase signal are also highly conserved domains of the Sirevirus genome.
      CONCLUSIONS: Our comparative analysis of retrotransposon genomes using advanced
      in silico methods highlighted the unique genome organization of Sireviruses.
      Their structure may dictate a life cycle with different regulation and
      transmission strategy compared to other Pseudoviridae, which may contribute
      towards their pattern of distribution within and across plants.

PMID- 20132533
TI  - Coevolution of activating and inhibitory receptors within mammalian
      carcinoembryonic antigen families.
AB  - BACKGROUND: Most rapidly evolving gene families are involved in immune responses
      and reproduction, two biological functions which have been assigned to the
      carcinoembryonic antigen (CEA) gene family. To gain insights into evolutionary
      forces shaping the CEA gene family we have analysed this gene family in 27
      mammalian species including monotreme and marsupial lineages. RESULTS:
      Phylogenetic analysis provided convincing evidence that the primordial CEA gene
      family in mammals consisted of five genes, including the immune inhibitory
      receptor-encoding CEACAM1 (CEA-related cell adhesion molecule) ancestor. Our
      analysis of the substitution rates within the nucleotide sequence which codes for
      the ligand binding domain of CEACAM1 indicates that the selection for
      diversification is, perhaps, a consequence of the exploitation of CEACAM1 by a
      variety of viral and bacterial pathogens as their cellular receptor. Depending on
      the extent of the amplification of an ancestral CEACAM1, the number of CEACAM1
      related genes varies considerably between mammalian species from less than five
      in lagomorphs to more than 100 in bats. In most analysed species, ITAM
      (immunoreceptor tyrosine-based activation motifs) or ITAM-like motif-containing
      proteins exist which contain Ig-V-like, ligand binding domains closely related to
      that of CEACAM1. Human CEACAM3 is one such protein which can function as a
      CEACAM1 decoy receptor in granulocytes by mediating the uptake and destruction of
      specific bacterial pathogens via its ITAM-like motif. The close relationship
      between CEACAM1 and its ITAM-encoding relatives appears to be maintained by gene
      conversion and reciprocal recombination. Surprisingly, secreted CEACAMs
      resembling immunomodulatory CEACAM1-related trophoblast-specific pregnancy
      specific glycoproteins (PSGs) found in humans and rodents evolved only in a
      limited set of mammals. The appearance of PSG-like genes correlates with invasive
      trophoblast growth in these species. CONCLUSIONS: These phylogenetic studies
      provide evidence that pathogen/host coevolution and a possible participation in
      fetal-maternal conflict processes led to a highly species-specific diversity of
      mammalian CEA gene families.

PMID- 20132534
TI  - Does GPs' self-perception of their professional role correspond to their social
      self-image?--a qualitative study from Germany.
AB  - BACKGROUND: There is a decline in the relative numbers of general practitioners
      in Germany. Earlier research showed that the professional relationship between
      general practitioners and specialists is overshadowed by conflicts which could
      influence medical students not to choose a career in general practice. The aim of
      the study is to analyse potential discrepancies between general practitioners'
      self-perception of their professional role and their social self-image in
      relation to medical specialists and to identify potential barriers that might
      prevent medical students from becoming a general practitioner. METHODS: A
      qualitative study design consisting of 16 interviews with general practitioners
      was chosen. Data analysis was carried out using the qualitative content analysis
      by Philipp Mayring. RESULTS: There is a discrepancy between general
      practitioners' professional self-perception and how they perceive they are viewed
      by specialists. General practitioners communicate a positive self-perception of
      their professional role. While general practitioners think that specialists in
      outpatient care have a positive view on general practice, it is assessed to be
      negative by specialists working in hospitals and as medical teachers. CONCLUSION:
      The negatively influenced social self-image may originate particularly from
      "badmouthing" general practitioners at universities and in hospitals.
      "Badmouthing" demonstrates the importance of the consideration of psychological
      aspects in medical teachers and hospital specialists acting as role models.
      Negative comments should be considered as an important factor in influencing
      medical students and trainees' career choices. These aspects should be more
      integrated in future medical education curricula.

PMID- 20132535
TI  - Gene ontology analysis for RNA-seq: accounting for selection bias.
AB  - We present GOseq, an application for performing Gene Ontology (GO) analysis on
      RNA-seq data. GO analysis is widely used to reduce complexity and highlight
      biological processes in genome-wide expression studies, but standard methods give
      biased results on RNA-seq data due to over-detection of differential expression
      for long and highly expressed transcripts. Application of GOseq to a prostate
      cancer data set shows that GOseq dramatically changes the results, highlighting
      categories more consistent with the known biology.

PMID- 20132537
TI  - Compliance with a three-day course of artesunate-mefloquine combination and
      baseline anti-malarial treatment in an area of Thailand with highly multidrug
      resistant falciparum malaria.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT) is presently recommended
      by the World Health Organization as first-line treatment for uncomplicated
      Plasmodium falciparum malaria in several countries, as a mean of prolonging the
      effectiveness of first-line malaria treatment regimens. A three-day course of
      artesunate-mefloquine (4 mg/kg body weight once daily for three consecutive days,
      plus 15 and 10 mg/kg body weight mefloquine on the first and second days) has
      been adopted by Malaria Control Programme of Thailand as first-line treatment for
      uncomplicated falciparum malaria all over the country since 2008. The
      gametocytocydal anti-malarial drug primaquine is administered at the dose of 30
      mg (0.6 mg/kg) on the last day. The aim of the present study was to assess
      patient compliance of this combination regimen when applied to field condition.
      METHODS: A total of 240 patients (196 males and 44 females) who were attending
      the malaria clinics in Mae-Sot, Tak Province and presenting with symptomatic
      acute uncomplicated falciparum malaria, with no reappearance of Plasmodium vivax
      parasitaemia during follow-up were included into the study. The first dose of the
      treatment was given to the patients under direct supervision. All patients were
      given the medication for self-treatment at home and were requested to come back
      for follow-up on day 3 of the initial treatment. Baseline (day 0) and day 3 whole
      blood mefloquine and plasma primaquine concentrations were determined by high
      performance liquid chromatography. RESULTS: Two patients had recrudescence on
      days 28 and 35. The Kaplan-Meier estimate of the 42-day efficacy rate of this
      combination regimen was 99.2% (238/240). Based on whole blood mefloquine and
      plasma primaquine concentrations on day 3 of the initial treatment, compliance
      with mefloquine and primaquine in this three-day artesunate-mefloquine
      combination regimen were 96.3% (207/215), and 98.5% (197/200), respectively.
      Baseline mefloquine and primaquine levels were observed in 24 and 16% of the
      patients. CONCLUSION: The current first-line treatment and a three-day
      combination regimen of artesunate-mefloquine provides excellent patient
      compliance with good efficacy and tolerability in the treatment of highly
      multidrug resistance falciparum malaria. Previous treatment with mefloquine and
      primaquine were common in this area.

PMID- 20132536
TI  - Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents.
AB  - Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes
      and activities of transcriptional factors involved in both cancer initiation and
      progression through alteration of either DNA or the structural components of
      chromatin. Recently, the role of gene repression through modulation such as
      acetylation in cancer patients has been clinically validated with several
      inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by
      FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive,
      persistent, or recurrent disease on or following two systemic therapies. Other
      inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275,
      valproic acid and LBH589 have also demonstrated therapeutic potential as
      monotherapy or combination with other anti-tumor drugs in CTCL and other
      malignancies. At least 80 clinical trials are underway, testing more than eleven
      different HDAC inhibitory agents including both hematological and solid
      malignancies. This review focuses on recent development in clinical trials
      testing HDAC inhibitors as anti-tumor agents.

PMID- 20132538
TI  - Clinimetric quality of the fire fighting simulation test as part of the Dutch
      fire fighters Workers' Health Surveillance.
AB  - BACKGROUND: Clinimetric data for the fire fighting simulation test (FFST), a new
      test proposed for the Workers' Health Surveillance (WHS) of Dutch fire fighters,
      were evaluated. METHODS: Twenty-one fire fighters took the FFST three times with
      one and three weeks between testing. Clinimetric quality was determined by means
      of reliability, agreement and validity. For reliability and agreement, the
      intraclass correlation coefficient (ICC), and standard error of measurement
      (SEM), were analysed. For construct validity, the tests from 45 fire fighters
      were correlated with their own and their supervisors' rated work ability.
      RESULTS: The ICCs were 0.56 and 0.79 at the one-week and three-week test-retest
      periods, respectively. Testing times ranged from 9 to 17 minutes; the SEMs were
      70 s at the one-week and 40 s at the three-week test-retest periods. The
      construct validity was moderate (-0.47 < or = r < or = -0.33; p < 0.05).
      CONCLUSIONS: The FFST was reliable with acceptable agreement after three weeks.
      Construct validity was moderate. We recommend using FFST as a part of the WHS for
      Dutch fire fighters. It is advised that fire fighters should perform the FFST
      once as a trial before judging their performance in testing time during the
      second performance.

PMID- 20132539
TI  - Community health insurance amidst abolition of user fees in Uganda: the view from
      policy makers and health service managers.
AB  - BACKGROUND: This paper investigates knowledge of Community Health Insurance (CHI)
      and the perception of its relevance by key policy makers and health service
      managers in Uganda. Community Health Insurance schemes currently operate in the
      private-not-for-profit sector, in settings where church-based facilities
      function. They operate in a wider policy environment where user fees in the
      public sector have been abolished. METHODS: Semi-structured interviews were
      conducted during the second half of 2007 with District Health Officers (DHOs) and
      senior staff of the Ministry of Health (MOH). The qualitative data collected were
      analyzed using the framework method, facilitated by EZ-Text software. RESULTS:
      There is poor knowledge and understanding of CHI activities by staff of the MOH
      headquarters and DHOs. However, a comparison of responses reveals a relatively
      high level of awareness of CHI principles among DHOs compared to that of MOH
      staff. All the DHOs in the districts with schemes had a good understanding of CHI
      principles compared to DHOs in districts without schemes. Out-of-pocket
      expenditure remains an important feature of health care financing in Uganda
      despite blanket abolition of user fees in government facilities. CONCLUSION: CHI
      is perceived as a relevant policy option and potential source of funds for health
      care. It is also considered a means of raising the quality of health care in both
      public and private health units. To assess whether it is also feasible to
      introduce CHI in the public sector, there is an urgent need to investigate the
      willingness and readiness of stakeholders, in particular high level political
      authorities, to follow this new path. The current ambiguity and contradictions in
      the health financing policy of the Uganda MOH need to be addressed and clarified.

PMID- 20132541
TI  - Endoplasmic reticulum protein 29 (ERp29), a protein related to sperm maturation
      is involved in sperm-oocyte fusion in mouse.
AB  - BACKGROUND: Sperm-oocyte fusion is a critical step in fertilization, which
      requires a series of proteins from both spermatozoa and oocyte to mediate
      membrane adhesion and subsequent fusion. A rat spermatozoa membrane protein is
      endoplasmic reticulum protein 29 (ERp29), which significantly increases on the
      sperm surface as well as in the cytoplasm of epididymal epithelia from caput to
      cauda as the sperm undergo epididymal maturation. Moreover, ERp29 facilitates
      viral infection via mediating membrane penetration. We determined if in addition
      to promoting sperm maturation ERp29 may also play a role in facilitating gamete
      fusion during the fertilization process. METHODS: Laser scanning confocal
      microscopy (LSCM) and Western blot analysis were employed to probe for ERp29
      protein in BALB/c mouse epididymal and acrosome-reacted spermatozoa. We prepared
      rabbit polyclonal antibodies against mouse recombinant ERp29 (rERp29) to
      characterize: 1) fertilization rate (FR); 2) fertilization index (FI); 3) sperm
      motility and 4) acrosome reaction (AR). RESULTS: Confocal microscopy indicated
      that ERp29 was partially localized at the sperm head of the epididymal caput as
      well as over the whole head and part of the principal piece of the tail region
      from the epididymal cauda. However, when the acrosome reacted, ERp29 remained in
      the equatorial and post-acrosomal regions of the sperm head, which is the initial
      site of sperm-oocyte membrane fusion. Such localization changes were confirmed
      based on the results of Western blot analysis. Furthermore, the antibodies
      against mouse rERp29 inhibited the spermatozoa from penetrating into the zona
      pellucida (ZP)-free oocytes. The functional blocking antibodies reduced both
      mouse sperm-oocyte FR and FI at concentrations of 100 and 200 micro g/ml compared
      with pre-immunized rabbit IgG or with anti-mouse recombinant
      bactericidal/permeability-increasing protein (BPI, a sperm surface protein
      unrelated to sperm-oocyte fusion) antibodies (100 micro g/ml), but they had no
      effect on sperm motility and AR. CONCLUSION: This study demonstrates that ERp29
      on mouse spermatozoa membrane changes during epididymal transit and AR.
      Accordingly, in mice this protein may be one of the important factors involved in
      sperm fertilization by facilitating sperm-oocyte membrane fusion.

PMID- 20132542
TI  - Health-related quality of life in diabetes: The associations of complications
      with EQ-5D scores.
AB  - BACKGROUND: The aim of this study was to describe how diabetes complications
      influence the health-related quality of life of individuals with diabetes using
      the individual EQ-5D dimensions and the EQ-5D index. METHODS: We mailed a
      questionnaire to 1,000 individuals with diabetes type 1 and 2 in Norway. The
      questionnaire had questions about socio-demographic characteristics, use of
      health care, diabetes complications and finally the EQ-5D descriptive system.
      Logistic regressions were used to explore determinants of responses in the EQ-5D
      dimensions, and robust linear regression was used to explore determinants of the
      EQ-5D index. RESULTS: In multivariate analyses the strongest determinants of
      reduced MOBILITY were neuropathy and ischemic heart disease. In the
      ANXIETY/DEPRESSION dimension of the EQ-5D, "fear of hypoglycaemia" was a strong
      determinant. For those without complications, the EQ-5D index was 0.90 (type 1
      diabetes) and 0.85 (type 2 diabetes). For those with complications, the EQ-5D
      index was 0.68 (type 1 diabetes) and 0.73 (type 2 diabetes). In the linear
      regression the factors with the greatest negative impact on the EQ-5D index were
      ischemic heart disease (type 1 diabetes), stroke (both diabetes types),
      neuropathy (both diabetes types), and fear of hypoglycaemia (type 2 diabetes).
      CONCLUSIONS: The EQ-5D dimensions and the EQ-5D seem capable of capturing the
      consequences of diabetes-related complications, and such complications may have
      substantial impact on several dimensions of health-related quality of life
      (HRQoL). The strongest determinants of reduced HRQoL in people with diabetes were
      ischemic heart disease, stroke and neuropathy.

PMID- 20132543
TI  - Translational medicine--doing it backwards.
AB  - In recent years the concept of "translational medicine" has been advanced in an
      attempt to catalyze the medical applications of basic biomedical research.
      However, there has been little discussion about the readiness of scientists
      themselves to respond to what we believe is a required new approach to scientific
      discovery if this new concept is to bear fruit. The present paradigm of
      hypothesis-driven research poorly suits the needs of biomedical research unless
      efforts are spent in identifying clinically relevant hypotheses. The dominant
      funding system favors hypotheses born from model systems and not humans,
      bypassing the Baconian principle of relevant observations and experimentation
      before hypotheses. Here, we argue that that this attitude has born two
      unfortunate results: lack of sufficient rigor in selecting hypotheses relevant to
      human disease and limitations of most clinical studies to certain outcome
      parameters rather than expanding knowledge of human pathophysiology; an illogical
      approach to translational medicine. If we wish to remain true to our
      responsibility and duty of performing research relevant to human disease, we must
      begin to think about fundamental new approaches.NIH is the nation's medical
      research agency--making important medical discoveries that improve health and
      save lives. NIH is the steward of medical and behavioral research for the Nation.
      Its mission is science in pursuit of fundamental knowledge about the nature and
      behavior of living systems and the application of that knowledge to extend
      healthy life and reduce the burdens of illness and disability 1.

PMID- 20132540
TI  - Cluster randomized trial in smoking cessation with intensive advice in diabetic
      patients in primary care. ITADI Study.
AB  - BACKGROUND: It is a priority to achieve smoking cessation in diabetic smokers,
      given that this is a group of patients with elevated cardiovascular risk.
      Furthermore, tobacco has a multiplying effect on micro and macro vascular
      complications. Smoking abstinence rates increase as the intensity of the
      intervention, length of the intervention and number and diversity of contacts
      with the healthcare professional during the intervention increases. However,
      there are few published studies about smoking cessation in diabetics in primary
      care, a level of healthcare that plays an essential role in these patients.
      Therefore, the aim of the present study is to evaluate the effectiveness of an
      intensive smoking cessation intervention in diabetic patients in primary care.
      METHODS/DESIGN: Cluster randomized trial, controlled and multicentric.
      Randomization unit: Primary Care Team. STUDY POPULATION: 546 diabetic smokers
      older than 14 years of age whose disease is controlled by one of the primary care
      teams in the study. OUTCOME MEASURES: Continuous tobacco abstinence (a person who
      has not smoked for at least six months and with a CO level of less than 6 ppm
      measured by a cooximeter) , evolution in the Prochaska and DiClemente's
      Transtheoretical Model of Change, number of cigarettes/day, length of the visit.
      Point of assessment: one- year post- inclusion in the study. INTERVENTION: Brief
      motivational interview for diabetic smokers at the pre-contemplation and
      contemplation stage, intensive motivational interview with pharmacotherapy for
      diabetic smokers in the preparation-action stage and reinforcing intevention in
      the maintenance stage. STATISTICAL ANALYSIS: A descriptive analysis of all
      variables will be done, as well as a multilevel logistic regression and a Poisson
      regression. All analyses will be done with an intention to treatment basis and
      will be fitted for potential confounding factors and variables of clinical
      importance. Statistical packages: SPSS15, STATA10 y HLM6. DISCUSSION: The present
      study will try to describe the profile of a diabetic smoker who receives the most
      benefit from an intensive intervention in primary care. The results will be
      useful for primary care professionals in their usual clinical practice. TRIAL
      REGISTRATION: Clinical Trials.gov Identifier: NCT00954967.

PMID- 20132545
TI  - Insulin-treated diabetes is not associated with increased mortality in critically
      ill patients.
AB  - INTRODUCTION: This was a planned substudy from the European observational Sepsis
      Occurrence in Acutely ill Patients (SOAP) study to investigate the possible
      impact of insulin-treated diabetes on morbidity and mortality in ICU patients.
      METHODS: The SOAP study was a cohort, multicenter, observational study which
      included data from all adult patients admitted to one of 198 participating ICUs
      from 24 European countries during the study period. For this substudy, patients
      were classified according to whether or not they had a known diagnosis of insulin
      treated diabetes mellitus. Outcome measures included the degree of organ
      dysfunction/failure as assessed by the sequential organ failure assessment (SOFA)
      score, the occurrence of sepsis syndromes and organ failure in the ICU, hospital
      and ICU length of stay, and all cause hospital and ICU mortality. RESULTS: Of the
      3147 patients included in the SOAP study, 226 (7.2%) had previously diagnosed
      insulin-treated diabetes mellitus. On admission, patients with insulin-treated
      diabetes were older, sicker, as reflected by higher simplified acute physiology
      system II (SAPS II) and SOFA scores, and more likely to be receiving hemodialysis
      than the other patients. During the ICU stay, more patients with insulin-treated
      diabetes required renal replacement therapy (hemodialysis or hemofiltration) than
      other patients. There were no significant differences in ICU or hospital lengths
      of stay or in ICU or hospital mortality between patients with or without insulin
      treated diabetes. Using a Cox proportional hazards regression analysis with
      hospital mortality censored at 28-days as the dependent factor, insulin-treated
      diabetes was not an independent predictor of mortality. CONCLUSIONS: Even though
      patients with a history of insulin-treated diabetes are more severely ill and
      more likely to have renal failure, insulin-treated diabetes is not associated
      with increased mortality in ICU patients.

PMID- 20132546
TI  - A diagnosis of conflict: theoretical barriers to integration in mental health
      services & their philosophical undercurrents.
AB  - This paper examines the philosophical substructure to the theoretical conflicts
      that permeate contemporary mental health care in the UK. Theoretical conflicts
      are treated here as those that arise among practitioners holding divergent
      theoretical orientations towards the phenomena being treated. Such conflicts,
      although steeped in history, have become revitalized by recent attempts at
      integrating mental health services that have forced diversely trained
      practitioners to work collaboratively together, often under one roof. Part I of
      this paper examines how the history of these conflicts can be understood as a
      tension between, on the one hand, the medical model and its use by the dominant
      profession of psychiatry, and on the other, those alternative models and
      practitioners in some way differentiated from the medical model camp. Examples
      will be given from recent policy and research to highlight the prevalence of this
      tension in contemporary practice. Part II of this paper explores the deeper
      commonalities that lay beneath the theoretical conflict outlined in Part I. These
      commonalities will be shown to be apart of a captivating framework that has
      continued to grip the conflict since its inception. By exposing this underlying
      framework--and the motivations inherent therein--the topic of integration appears
      in wholly different light, allowing a renewed philosophical basis for integration
      to emerge.

PMID- 20132544
TI  - Origin of the cell nucleus, mitosis and sex: roles of intracellular coevolution.
AB  - BACKGROUND: The transition from prokaryotes to eukaryotes was the most radical
      change in cell organisation since life began, with the largest ever burst of gene
      duplication and novelty. According to the coevolutionary theory of eukaryote
      origins, the fundamental innovations were the concerted origins of the
      endomembrane system and cytoskeleton, subsequently recruited to form the cell
      nucleus and coevolving mitotic apparatus, with numerous genetic eukaryotic
      novelties inevitable consequences of this compartmentation and novel DNA
      segregation mechanism. Physical and mutational mechanisms of origin of the
      nucleus are seldom considered beyond the long-standing assumption that it
      involved wrapping pre-existing endomembranes around chromatin. Discussions on the
      origin of sex typically overlook its association with protozoan entry into
      dormant walled cysts and the likely simultaneous coevolutionary, not sequential,
      origin of mitosis and meiosis. RESULTS: I elucidate nuclear and mitotic
      coevolution, explaining the origins of dicer and small centromeric RNAs for
      positionally controlling centromeric heterochromatin, and how 27 major features
      of the cell nucleus evolved in four logical stages, making both mechanisms and
      selective advantages explicit: two initial stages (origin of 30 nm chromatin
      fibres, enabling DNA compaction; and firmer attachment of endomembranes to
      heterochromatin) protected DNA and nascent RNA from shearing by novel molecular
      motors mediating vesicle transport, division, and cytoplasmic motility. Then
      octagonal nuclear pore complexes (NPCs) arguably evolved from COPII coated
      vesicle proteins trapped in clumps by Ran GTPase-mediated cisternal fusion that
      generated the fenestrated nuclear envelope, preventing lethal complete cisternal
      fusion, and allowing passive protein and RNA exchange. Finally, plugging NPC
      lumens by an FG-nucleoporin meshwork and adopting karyopherins for
      nucleocytoplasmic exchange conferred compartmentation advantages. These
      successive changes took place in naked growing cells, probably as indirect
      consequences of the origin of phagotrophy. The first eukaryote had 1-2 cilia and
      also walled resting cysts; I outline how encystation may have promoted the origin
      of meiotic sex. I also explain why many alternative ideas are inadequate.
      CONCLUSION: Nuclear pore complexes are evolutionary chimaeras of endomembrane-
      and mitosis-related chromatin-associated proteins. The keys to understanding
      eukaryogenesis are a proper phylogenetic context and understanding organelle
      coevolution: how innovations in one cell component caused repercussions on
      others.

PMID- 20132547
TI  - Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion,
      migration, and invasion.
AB  - BACKGROUND: Factors responsible for invasive and metastatic progression of
      prostate cancer (PCa) remain largely unknown. Previously, we reported cloning of
      prosaposin (PSAP) and its genomic amplification and/or overexpression in several
      androgen-independent metastatic PCa cell lines and lymph node metastases. PSAP is
      the lysosomal precursor of saposins, which serve as activators for lysosomal
      hydrolases involved in the degradation of ceramide (Cer) and other sphingolipids.
      RESULTS: Our current data show that, in metastatic PCa cells, stable down
      modulation of PSAP by RNA-interference via a lysosomal proteolysis-dependent
      pathway decreased beta1A-integrin expression, its cell-surface clustering, and
      adhesion to basement membrane proteins; led to disassembly of focal adhesion
      complex; and decreased phosphorylative activity of focal adhesion kinase and its
      downstream adaptor molecule, paxillin. Cathepsin D (CathD) expression and
      proteolytic activity, migration, and invasion were also significantly decreased
      in PSAP knock-down cells. Transient-transfection studies with beta1A integrin- or
      CathD-siRNA oligos confirmed the cause and effect relationship between PSAP and
      CathD or PSAP and Cer-beta1A integrin, regulating PCa cell migration and
      invasion. CONCLUSION: Our findings suggest that by a coordinated regulation of
      Cer levels, CathD and beta1A-integrin expression, and attenuation of "inside-out"
      integrin-signaling pathway, PSAP is involved in PCa invasion and therefore might
      be used as a molecular target for PCa therapy.

PMID- 20132548
TI  - Diffusion is capable of translating anisotropic apoptosis initiation into a
      homogeneous execution of cell death.
AB  - BACKGROUND: Apoptosis is an essential cell death process throughout the entire
      life span of all metazoans and its deregulation in humans has been implicated in
      many proliferative and degenerative diseases. Mitochondrial outer membrane
      permeabilisation (MOMP) and activation of effector caspases are key processes
      during apoptosis signalling. MOMP can be subject to spatial coordination in human
      cancer cells, resulting in intracellular waves of cytochrome-c release. To
      investigate the consequences of these spatial anisotropies in mitochondrial
      permeabilisation on subsequent effector caspase activation, we devised a
      mathematical reaction-diffusion model building on a set of partial differential
      equations. RESULTS: Reaction-diffusion modelling suggested that even if strong
      spatial anisotropies existed during mitochondrial cytochrome c release, these
      would be eliminated by free diffusion of the cytosolic proteins that instantiate
      the apoptosis execution network. Experimentally, rapid sampling of mitochondrial
      permeabilisation and effector caspase activity in individual HeLa cervical cancer
      cells confirmed predictions of the reaction-diffusion model and demonstrated that
      the signalling network of apoptosis execution could efficiently translate spatial
      anisotropies in mitochondrial permeabilisation into a homogeneous effector
      caspase response throughout the cytosol. Further systems modelling suggested that
      a more than 10,000-fold impaired diffusivity would be required to maintain
      spatial anisotropies as observed during mitochondrial permeabilisation until the
      time effector caspases become activated. CONCLUSIONS: Multi-protein diffusion
      efficiently contributes to eliminating spatial asynchronies which are present
      during the initiation of apoptosis execution and thereby ensures homogeneous
      apoptosis execution throughout the entire cell body. For previously reported
      biological scenarios in which effector caspase activity was shown to be targeted
      selectively to specific subcellular regions additional mechanisms must exist that
      limit or spatially coordinate caspase activation and/or protect diffusing soluble
      caspase substrates from unwanted proteolysis.

PMID- 20132549
TI  - Abdominal muscle fatigue following exercise in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: In patients with chronic obstructive pulmonary disease, a restriction
      on maximum ventilatory capacity contributes to exercise limitation. It has been
      demonstrated that the diaphragm in COPD is relatively protected from fatigue
      during exercise. Because of expiratory flow limitation the abdominal muscles are
      activated early during exercise in COPD. This adds significantly to the work of
      breathing and may therefore contribute to exercise limitation. In healthy
      subjects, prior expiratory muscle fatigue has been shown itself to contribute to
      the development of quadriceps fatigue. It is not known whether fatigue of the
      abdominal muscles occurs during exercise in COPD. METHODS: Twitch gastric
      pressure (TwT10Pga), elicited by magnetic stimulation over the 10th thoracic
      vertebra and twitch transdiaphragmatic pressure (TwPdi), elicited by bilateral
      anterolateral magnetic phrenic nerve stimulation were measured before and after
      symptom-limited, incremental cycle ergometry in patients with COPD. RESULTS:
      Twenty-three COPD patients, with a mean (SD) FEV1 40.8(23.1)% predicted, achieved
      a mean peak workload of 53.5(15.9) W. Following exercise, TwT10Pga fell from
      51.3(27.1) cmH2O to 47.4(25.2) cmH2O (p = 0.011). TwPdi did not change
      significantly; pre 17.0(6.4) cmH2O post 17.5(5.9) cmH2O (p = 0.7). Fatiguers,
      defined as having a fall TwT10Pga > or = 10% had significantly worse lung gas
      transfer, but did not differ in other exercise parameters. CONCLUSIONS: In
      patients with COPD, abdominal muscle but not diaphragm fatigue develops following
      symptom limited incremental cycle ergometry. Further work is needed to establish
      whether abdominal muscle fatigue is relevant to exercise limitation in COPD,
      perhaps indirectly through an effect on quadriceps fatigability.

PMID- 20132550
TI  - CNV Workshop: an integrated platform for high-throughput copy number variation
      discovery and clinical diagnostics.
AB  - BACKGROUND: Recent studies have shown that copy number variations (CNVs) are
      frequent in higher eukaryotes and associated with a substantial portion of
      inherited and acquired risk for various human diseases. The increasing
      availability of high-resolution genome surveillance platforms provides
      opportunity for rapidly assessing research and clinical samples for CNV content,
      as well as for determining the potential pathogenicity of identified variants.
      However, few informatics tools for accurate and efficient CNV detection and
      assessment currently exist. RESULTS: We developed a suite of software tools and
      resources (CNV Workshop) for automated, genome-wide CNV detection from a variety
      of SNP array platforms. CNV Workshop includes three major components: detection,
      annotation, and presentation of structural variants from genome array data. CNV
      detection utilizes a robust and genotype-specific extension of the Circular
      Binary Segmentation algorithm, and the use of additional detection algorithms is
      supported. Predicted CNVs are captured in a MySQL database that supports cohort
      based projects and incorporates a secure user authentication layer and user/admin
      roles. To assist with determination of pathogenicity, detected CNVs are also
      annotated automatically for gene content, known disease loci, and gene-based
      literature references. Results are easily queried, sorted, filtered, and
      visualized via a web-based presentation layer that includes a GBrowse-based
      graphical representation of CNV content and relevant public data, integration
      with the UCSC Genome Browser, and tabular displays of genomic attributes for each
      CNV. CONCLUSIONS: To our knowledge, CNV Workshop represents the first cohesive
      and convenient platform for detection, annotation, and assessment of the
      biological and clinical significance of structural variants. CNV Workshop has
      been successfully utilized for assessment of genomic variation in healthy
      individuals and disease cohorts and is an ideal platform for coordinating
      multiple associated projects. AVAILABILITY AND IMPLEMENTATION: Available on the
      web at: http://sourceforge.net/projects/cnv.

PMID- 20132551
TI  - Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E
      protein derived from a naturally infected patient.
AB  - BACKGROUND: Antibodies produced in response to infection with any of the four
      serotypes of dengue virus generally provide homotypic immunity. However, prior
      infection or circulating maternal antibodies can also mediate a non-protective
      antibody response that can enhance the course of disease in a subsequent
      heterotypic infection. Naturally occurring human monoclonal antibodies can help
      us understand the protective and pathogenic roles of the humoral immune system in
      dengue virus infection. RESULTS: Epstein-Barr Virus (EBV) transformation of B
      cells isolated from the peripheral blood of a human subject with previous dengue
      infection was performed. B cell cultures were screened by ELISA for antibodies to
      dengue (DENV) envelope (E) protein. ELISA positive cultures were cloned by
      limiting dilution. Three IgG1 human monoclonal antibodies (HMAbs) were purified
      and their binding specificity to E protein was verified by ELISA and biolayer
      interferometry. Neutralization and enhancement assays were conducted in
      epithelial and macrophage-like cell lines, respectively. All three HMAbs bound to
      E from at least two of the four DENV serotypes, one of the HMAbs was
      neutralizing, and all were able to enhance DENV infection. CONCLUSIONS: HMAbs
      against DENV can be successfully generated by EBV transformation of B cells from
      patients at least two years after naturally acquired DENV infections. These
      antibodies show different patterns of cross-reactivity, neutralizing, and
      enhancement activity.

PMID- 20132552
TI  - Mining protein loops using a structural alphabet and statistical exceptionality.
AB  - BACKGROUND: Protein loops encompass 50% of protein residues in available three
      dimensional structures. These regions are often involved in protein functions,
      e.g. binding site, catalytic pocket... However, the description of protein loops
      with conventional tools is an uneasy task. Regular secondary structures, helices
      and strands, have been widely studied whereas loops, because they are highly
      variable in terms of sequence and structure, are difficult to analyze. Due to
      data sparsity, long loops have rarely been systematically studied. RESULTS: We
      developed a simple and accurate method that allows the description and analysis
      of the structures of short and long loops using structural motifs without
      restriction on loop length. This method is based on the structural alphabet HMM
      SA. HMM-SA allows the simplification of a three-dimensional protein structure
      into a one-dimensional string of states, where each state is a four-residue
      prototype fragment, called structural letter. The difficult task of the
      structural grouping of huge data sets is thus easily accomplished by handling
      structural letter strings as in conventional protein sequence analysis. We
      systematically extracted all seven-residue fragments in a bank of 93000 protein
      loops and grouped them according to the structural-letter sequence, named
      structural word. This approach permits a systematic analysis of loops of all
      sizes since we consider the structural motifs of seven residues rather than
      complete loops. We focused the analysis on highly recurrent words of loops
      (observed more than 30 times). Our study reveals that 73% of loop-lengths are
      covered by only 3310 highly recurrent structural words out of 28274 observed
      words). These structural words have low structural variability (mean RMSd of 0.85
      A). As expected, half of these motifs display a flanking-region preference but
      interestingly, two thirds are shared by short (less than 12 residues) and long
      loops. Moreover, half of recurrent motifs exhibit a significant level of amino
      acid conservation with at least four significant positions and 87% of long loops
      contain at least one such word. We complement our analysis with the detection of
      statistically over-represented patterns of structural letters as in conventional
      DNA sequence analysis. About 30% (930) of structural words are over-represented,
      and cover about 40% of loop lengths. Interestingly, these words exhibit lower
      structural variability and higher sequential specificity, suggesting structural
      or functional constraints. CONCLUSIONS: We developed a method to systematically
      decompose and study protein loops using recurrent structural motifs. This method
      is based on the structural alphabet HMM-SA and not on structural alignment and
      geometrical parameters. We extracted meaningful structural motifs that are found
      in both short and long loops. To our knowledge, it is the first time that pattern
      mining helps to increase the signal-to-noise ratio in protein loops. This finding
      helps to better describe protein loops and might permit to decrease the
      complexity of long-loop analysis. Detailed results are available at
      http://www.mti.univ-paris-diderot.fr/publication/supplementary/2009/ACCLoop/.

PMID- 20132554
TI  - Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site
      promoter methylation.
AB  - BACKGROUND: Epigenetic changes associated with promoter DNA methylation results
      in silencing of several tumor suppressor genes that lead to increased risk for
      tumor formation and for progression of the cancer. METHODS: Methylation specific
      PCR (MSP) and bisulfite sequencing were used for determination of proapoptotic
      gene Caspase 8 (CASP8) and the tumor suppressor gene maspin promoter methylation
      in four breast cancer and two non-tumorigenic breast cell lines. Involvement of
      histone H3 methylation in those cell lines were examined by CHIP assay. RESULTS:
      The CpG sites in the promoter region of CASP8 and maspin were methylated in all
      four breast cancer cell lines but not in two non-tumorigenic breast cell lines.
      Demethylation agent 5-aza-2'-deoxycytidine (5-aza-dc) selectively inhibits DNA
      methyltransferases, DNMT3a and DNMT3b, and restored CASP8 and maspin gene
      expression in breast cancer cells. 5-aza-dc also reduced histone H3k9me2
      occupancy on CASP8 promoter in SKBR3cells, but not in MCF-7 cells. Combination of
      histone deacetylase inhibitor Trichostatin A (TSA) and 5-aza-dc significant
      decrease in nuclear expression of Di-methyl histone H3-Lys27 and slight increase
      in acetyl histone H3-Lys9 in MCF-7 cells. CASP8 mRNA and protein level in MCF-7
      cells were increased by the 5-aza-dc in combination with TSA. Data from our study
      also demonstrated that treatment with 5-FU caused a significant increase in
      unmethylated CASP8 and in CASP8 mRNA in all 3 cancer lines. CONCLUSIONS: CASP8
      and maspin expression were reduced in breast cancer cells due to promoter
      methylation. Selective application of demethylating agents could offer novel
      therapeutic opportunities in breast cancer.

PMID- 20132553
TI  - Hematopoietic stem cells and retroviral infection.
AB  - Retroviral induced malignancies serve as ideal models to help us better
      understand the molecular mechanisms associated with the initiation and
      progression of leukemogenesis. Numerous retroviruses including AEV, FLV, M-MuLV
      and HTLV-1 have the ability to infect hematopoietic stem and progenitor cells,
      resulting in the deregulation of normal hematopoiesis and the development of
      leukemia/lymphoma. Research over the last few decades has elucidated similarities
      between retroviral-induced leukemogenesis, initiated by deregulation of innate
      hematopoietic stem cell traits, and the cancer stem cell hypothesis. Ongoing
      research in some of these models may provide a better understanding of the
      processes of normal hematopoiesis and cancer stem cells. Research on retroviral
      induced leukemias and lymphomas may identify the molecular events which trigger
      the initial cellular transformation and subsequent maintenance of hematologic
      malignancies, including the generation of cancer stem cells. This review focuses
      on the role of retroviral infection in hematopoietic stem cells and the
      initiation, maintenance and progression of hematological malignancies.

PMID- 20132555
TI  - A case report of pseudoprogression followed by complete remission after proton
      beam irradiation for a low-grade glioma in a teenager: the value of dynamic
      contrast-enhanced MRI.
AB  - A fourteen years-old boy was treated post-operatively with proton therapy for a
      recurrent low-grade oligodendroglioma located in the tectal region. Six months
      after the end of irradiation (RT), a new enhancing lesion appeared within the
      radiation fields. To differentiate disease progression from radiation-induced
      changes, dynamic susceptibility contrast-enhanced (DSCE) MRI was used with a T2*
      sequence to study perfusion and permeability characteristics simultaneously.
      Typically, the lesion showed hypoperfusion and hyperpermeability compared to the
      controlateral normal brain. Without additional treatment but a short course of
      steroids, the image disappeared over a six months period allowing us to conclude
      for a pseudo-progression. The patient is alive in complete remission more than 2
      years post-RT.

PMID- 20132556
TI  - Microembolic signals and strategy to prevent gas embolism during extracorporeal
      membrane oxygenation.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) supplies systemic blood
      perfusion and gas exchange in patients with cardiopulmonary failure. The current
      literature lacks of papers reporting the possible risks of microembolism among
      the complications of this treatment.In this study we present our preliminary
      experience on brain blood flow velocity and emboli detection through the
      transcranial Doppler monitoring during ECMO. METHODS: Six patients suffering of
      heart failure, four after cardiac surgery and two after cardiopulmonary
      resuscitation were treated with ECMO and submitted to transcranial doppler
      monitoring to accomplish the neurophysiological evaluation for coma.Four patients
      had a full extracorporeal flow supply while in the remaining two patients the
      support was maintained 50% in respect to normal demand.All patients had a
      bilateral transcranial brain blood flow monitoring for 15 minutes during the
      first clinical evaluation. RESULTS: Microembolic signals were detected only in
      patients with the full extracorporeal blood flow supply due to air embolism.
      CONCLUSIONS: We established that the microembolic load depends on gas embolism
      from the central venous lines and on the level of blood flow assistance.The gas
      microemboli that enter in the blood circulation and in the extracorporeal
      circuits are not removed by the membrane oxygenator filter.Maximum care is
      required in drugs and fluid infusion of this kind of patients as a possible
      source of microemboli. This harmful phenomenon may be overcome adding an air
      filter device to the intravenous catheters.

PMID- 20132557
TI  - CyberKnife radiosurgery for inoperable stage IA non-small cell lung cancer: 18F
      fluorodeoxyglucose positron emission tomography/computed tomography serial tumor
      response assessment.
AB  - OBJECTIVE: To report serial 18F-fluorodeoxyglucose (18F-FDG) positron emission
      tomography (PET)/computed tomography (CT) tumor response following CyberKnife
      radiosurgery for stage IA non-small cell lung cancer (NSCLC). METHODS: Patients
      with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved
      study. Targeting was based on 3-5 gold fiducial markers implanted in or near
      tumors. Gross tumor volumes (GTVs) were contoured using lung windows; margins
      were expanded by 5 mm to establish the planning treatment volumes (PTVs). Doses
      ranged from 42-60 Gy in 3 equal fractions. 18F-FDG PET/CT was performed prior to
      and at 3-6-month, 9-15 months and 18-24 months following treatment. The tumor
      maximum standardized uptake value (SUV(max)) was recorded for each time point.
      RESULTS: Twenty patients with an average maximum tumor diameter of 2.2 cm were
      treated over a 3-year period. A mean dose of 51 Gy was delivered to the PTV in 3
      to 11 days (mean, 7 days). The 30-Gy isodose contour extended an average of 2 cm
      from the GTV. At a median follow-up of 43 months, the 2-year Kaplan-Meier overall
      survival estimate was 90% and the local control estimate was 95%. Mean tumor
      SUV(max) before treatment was 6.2 (range, 2.0 to 10.7). During early follow-up
      the mean tumor SUV(max) remained at 2.3 (range, 1.0 to 5.7), despite transient
      elevations in individual tumor SUV(max) levels attributed to peritumoral
      radiation-induced pneumonitis visible on CT imaging. At 18-24 months the mean
      tumor SUV(max) for controlled tumors was 2.0, with a narrow range of values
      (range, 1.5 to 2.8). A single local failure was confirmed at 24 months in a
      patient with an elevated tumor SUV(max) of 8.4. CONCLUSION: Local control and
      survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional.
      Early transient increases in tumor SUV(max) are likely related to radiation
      induced pneumonitis. Tumor SUV(max) values return to background levels at 18-24
      months, enhancing 18F-FDG PET/CT detection of local failure. The value of 18F-FDG
      PET/CT imaging for surveillance following lung SBRT deserves further study.

PMID- 20132558
TI  - Differential genome-wide gene expression profiling of bovine largest and second
      largest follicles: identification of genes associated with growth of dominant
      follicles.
AB  - BACKGROUND: Bovine follicular development is regulated by numerous molecular
      mechanisms and biological pathways. In this study, we tried to identify
      differentially expressed genes between largest (F1) and second-largest follicles
      (F2), and classify them by global gene expression profiling using a combination
      of microarray and quantitative real-time PCR (QPCR) analysis. The follicular
      status of F1 and F2 were further evaluated in terms of healthy and atretic
      conditions by investigating mRNA localization of identified genes. METHODS:
      Global gene expression profiles of F1 (10.7 +/- 0.7 mm) and F2 (7.8 +/- 0.2 mm)
      were analyzed by hierarchical cluster analysis and expression profiles of 16
      representative genes were confirmed by QPCR analysis. In addition, localization
      of six identified transcripts was investigated in healthy and atretic follicles
      using in situ hybridization. The healthy or atretic condition of examined
      follicles was classified by progesterone and estradiol concentrations in
      follicular fluid. RESULTS: Hierarchical cluster analysis of microarray data
      classified the follicles into two clusters. Cluster A was composed of only F2 and
      was characterized by high expression of 31 genes including IGFBP5, whereas
      cluster B contained only F1 and predominantly expressed 45 genes including CYP19
      and FSHR. QPCR analysis confirmed AMH, CYP19, FSHR, GPX3, PlGF, PLA2G1B, SCD and
      TRB2 were greater in F1 than F2, while CCL2, GADD45A, IGFBP5, PLAUR, SELP, SPP1,
      TIMP1 and TSP2 were greater in F2 than in F1. In situ hybridization showed that
      AMH and CYP19 were detected in granulosa cells (GC) of healthy as well as atretic
      follicles. PlGF was localized in GC and in the theca layer (TL) of healthy
      follicles. IGFBP5 was detected in both GC and TL of atretic follicles. GADD45A
      and TSP2 were localized in both GC and TL of atretic follicles, whereas healthy
      follicles expressed them only in GC. CONCLUSION: We demonstrated that global gene
      expression profiling of F1 and F2 clearly reflected a difference in their
      follicular status. Expression of stage-specific genes in follicles may be closely
      associated with their growth or atresia. Several genes identified in this study
      will provide intriguing candidates for the determination of follicular growth.

PMID- 20132559
TI  - IkappaBalpha polymorphism at promoter region (rs2233408) influences the
      susceptibility of gastric cancer in Chinese.
AB  - BACKGROUND: Nuclear factor of kappa B inhibitor alpha (I kappaB alpha) protein is
      implicated in regulating a variety of cellular process from inflammation to
      tumorigenesis. The objective of this study was to investigate the susceptibility
      of rs2233408 T/C genotype in the promoter region of I kappaB alpha to gastric
      cancer and the association of this polymorphism with clinicopathologic variables
      in gastric cancer patients. METHODS: A population-based case-control study was
      conducted between 1999 and 2006 in Guangdong Province, China. A total of 564
      gastric cancer patients and 566 healthy controls were enrolled in this study.
      rs2233408 genotypes in I kappaB alpha were analyzed by TaqMan SNP genotyping
      assay. RESULTS: Both rs2233408 T homozygote (TT) and T heterozygotes (TC and TT)
      had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069
      0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037),
      compared with rs2233408 C homozygote (CC). rs2233408 T heterozygotes were
      significantly associated with reduced risk of intestinal-type gastric cancer with
      ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014), but not with the diffuse or mix
      type of gastric cancer. The association between rs2233408 T heterozygotes and
      gastric cancer appeared more apparent in the older patients (age>40) (OR = 0.674,
      95% CI = 0.484-0.939, P = 0.02). rs2233408 T heterozygotes was associated with
      non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006), but not
      with cardiac gastric cancer. However, rs2233408 polymorphism was not associated
      with the prognosis of gastric cancer patients. CONCLUSIONS: I kappaB alpha
      rs2233408 T heterozygotes were associated with reduced risk of gastric cancer,
      especially for the development of certain subtypes of gastric cancer in Chinese
      population.

PMID- 20132560
TI  - Monkey hybrid stem cells develop cellular features of Huntington's disease.
AB  - BACKGROUND: Pluripotent stem cells that are capable of differentiating into
      different cell types and develop robust hallmark cellular features are useful
      tools for clarifying the impact of developmental events on neurodegenerative
      diseases such as Huntington's disease. Additionally, a Huntington's cell model
      that develops robust pathological features of Huntington's disease would be
      valuable for drug discovery research. RESULTS: To test this hypothesis, a
      pluripotent Huntington's disease monkey hybrid cell line (TrES1) was established
      from a tetraploid Huntington's disease monkey blastocyst generated by the fusion
      of transgenic Huntington's monkey skin fibroblast and a wild-type non-transgenic
      monkey oocyte. The TrES1 developed key Huntington's disease cellular pathological
      features that paralleled neural development. It expressed mutant huntingtin and
      stem cell markers, was capable of differentiating to neural cells, and developed
      teratoma in severely compromised immune deficient (SCID) mice. Interestingly, the
      expression of mutant htt, the accumulation of oligomeric mutant htt and the
      formation of intranuclear inclusions paralleled neural development in vitro , and
      even mutant htt was ubiquitously expressed. This suggests the development of
      Huntington's disease cellular features is influenced by neural developmental
      events. CONCLUSIONS: Huntington's disease cellular features is influenced by
      neural developmental events. These results are the first to demonstrate that a
      pluripotent stem cell line is able to mimic Huntington's disease progression that
      parallels neural development, which could be a useful cell model for
      investigating the developmental impact on Huntington's disease pathogenesis.

PMID- 20132561
TI  - Spondylodiscitis and an aortic aneurysm due to Campylobacter coli.
AB  - Campylobacter coli is a rare cause of bacteremia. We report here the first case
      of C.coli spondylodiscitis complicated by an aortic aneurysm. Outcome was
      favourable with surgery and antibiotic therapy.

PMID- 20132562
TI  - [Experimental treatment or medical research?].
AB  - If in the Netherlands a doctor offers experimental treatment to patients purely
      because it is in their patients' best interest, thus without serving any
      scientific goal, this does not fall under the scope of the Dutch Medical Research
      involving Human Subjects Act (WMO), but under specifications on the medical
      treatment agreement (WGBO) laid down in the civil code. If the doctor deviates
      from professional standards and the current protocols and guidelines, he or she
      must be able to account for that. The WMO applies as soon as doctors offer
      experimental treatments within the context of a research protocol, or perform
      research interventions such as randomization or the removal of extra tissue. Then
      specific provisions regarding medical ethical protocol review and written
      informed consent should be met.

PMID- 20132563
TI  - [Complaints about bureaucracy in health care? Time for a proactive medical
      profession].
AB  - Health care is in profound transition, its organization changing from being
      service-oriented to outcomes-oriented. Doctors are complaining of too much
      bureaucracy. However, the increasing complexity of healthcare demands
      rationalization, standardization and optimization of processes. At the same time,
      the practice of medicine is increasingly politicized. If doctors are the key to
      healthcare reform, how then are they to be motivated? It is imperative that they
      become more proactive and engage in leadership. They are the first to ensure that
      the main goals of medicine remain evidence-based prevention and cure of disease.
      Passivity will create opportunity for bureaucracy.

PMID- 20132564
TI  - [Diagnostic image. A man with tongue deviation following a motorcycle accident].
AB  - A 49-year-old man complained of headache, dysarthria and difficulty in swallowing
      following a motorcycle accident. He had a tongue deviation to the right due to a
      traumatic lesion of the right hypoglossal nerve which was caused by a right
      occipital condyle fracture.

PMID- 20132565
TI  - [Fewer breech deliveries after implementation of a modified cephalic version
      protocol].
AB  - AIM: To investigate the effect of implementation of a number of process policy
      guidelines (protocol), on the success rate of external cephalic version (ECV) for
      breech presentation. DESIGN: Prospective study. METHODS: During a 3-year period
      (2004-2006) a standardized protocol for an ECV consultation was developed,
      evaluated and adapted. After implementing this modified protocol as 'process
      policy guidelines', the effect on the rate of successful ECV was prospectively
      evaluated during the period 1 January 2007-31 July 2008. Success was defined as
      cephalic presentation (ultrasound) immediately after ECV. A secondary outcome
      measure was the elective caesarean section rate for breech presentation. RESULTS:
      The rate of successful ECV increased significantly from 47% (110/236 pregnant
      women) in the period January 2004-December 2006 to 61% (85/139, p = 0.006) in the
      period January 2007-July 2008. Patient characteristics were similar in both
      groups, with the exception of 2 subgroups of term of version. The increase was
      preferentially found in nulliparous and multiparous women with frank breech.
      Nulliparity, frank breech, anterior placenta and low birth weight were associated
      with a lower success rate of ECV. The term of pregnancy at which ECV was
      performed did not seem to affect the success rate. Implementing the process
      policy guidelines increased the number of cephalic presentations at delivery and
      decreased the rate of elective caesarean sections for breech presentation from
      39% to 27% (p = 0.03). The number needed to treat to prevent 1 elective caesarean
      section by ECV according to the process policy guidelines was 8. CONCLUSION:
      After implementation of the process policy guidelines, the success rate of ECV
      increased considerably. The rate of elective caesarean section for breech
      presentation declined. These findings are in favour of establishing specialized
      ECV centres in the Netherlands.

PMID- 20132567
TI  - [Two new treatments for haemorrhoids. Doppler-guided haemorrhoidal artery
      ligation and stapled anopexy].
AB  - Haemorrhoids occur in approximately 30% of the population. Commonly occurring
      complaints include blood loss, pruritus, hygiene problems and soiling. A high
      fibre diet, with dietary-fiber supplementation if required, often resolves the
      symptoms. When symptoms are not resolved, the next step is rubber band ligation:
      a safe and easy procedure. In the long term, the result of rubber band ligation
      is often unsatisfactory. Haemorrhoidectomy was formerly the only alternative.
      Haemorrhoidectomy can be accompanied by serious complications, such as disabling
      pain and incontinence. Haemorrhoidectomy was therefore considered obsolete by the
      Dutch Institute for Healthcare Improvement (CBO) guideline of 1994. Today new
      operative procedures are available: Doppler-guided haemorrhoidal artery ligation
      (DG-HAL) and stapled anopexy. Both techniques are safe and yield good results.
      Moreover, these techniques cause little postoperative pain. DG-HAL and stapled
      anopexy offer an alternative for patients whose symptoms are not resolved by
      dietary-fiber supplementation and rubber band ligation.

PMID- 20132568
TI  - [Severe vitamin D deficiency and hypocalcaemia after bariatric surgery].
AB  - A 60-year-old man was referred to the accident and emergency department because
      of muscle cramps and retrosternal pain. Laboratory tests revealed severe vitamin
      D deficiency and hypocalcaemia. The patient had undergone bariatric surgery
      several years previously. Disturbances in fat-soluble vitamins and in minerals
      are a frequent complication after bariatric procedures. Recognition and treatment
      of these disorders is very important.

PMID- 20132569
TI  - [Severe, subacute axonal polyneuropathy due to hypophosphatemia].
AB  - A 46-year-old man receiving tube feeding because of anorexia and weight loss
      developed progressive neurological symptoms initially resembling Guillain-Barre
      syndrome. Eventually axonal neuropathy due to severe hypophosphatemia was
      diagnosed. Hypophosphatemia can be caused by the so-called refeeding syndrome,
      which may occur in patients who start feeding after prolonged fasting. The
      neurological manifestations of hypophosphatemia are reversible if oral or
      intravenous suppletion of phosphate is started in time. Recognizing the refeeding
      syndrome is crucial in making a timely diagnosis.

PMID- 20132570
TI  - [Hallucinations attributed to djinns].
AB  - Individuals with an Islamic background who suffer from hallucinations often
      attribute these to djinns, invisible beings. The treatment of these
      hallucinations is complicated by the patients' reluctance to discuss them, and by
      their doubts concerning the usefulness of a biomedical treatment for a problem
      which they experience as metaphysical in nature. In this clinical lesson, we
      present case studies of three Moroccan patients who attributed their
      hallucinations to djinns. The first was a 30-year-old factory worker whose
      compulsive complaints had started when he saw a white figure in the basement who
      asked him 'What are you doing here?' The psychiatric diagnosis was obsessive
      compulsive disorder. The patient was prescribed cognitive behavioural therapy, an
      SSRI and a consultation by the imam, but he refused. The second patient was a 25
      year-old unemployed man, who had auditory hallucinations, delusions, behavioural
      problems, and alcohol and cannabis abuse. He heard voices which he attributed to
      maleficent djinns. He was diagnosed with schizophrenia, but his compliance with
      antipsychotics was insufficient. The imam who was consulted reassured him that
      his complaints were not caused by djinns. After prolonged treatment with
      clozapine and cutting down on cannabis use the patient recovered sufficiently to
      be discharged. The third patient was a 26-year-old unemployed woman who was
      hearing voices that her imam thought were caused by a djinn. She was examined
      because of serious self-mutilation and was diagnosed with a schizoaffective
      disorder. Treatment with an antipsychotic, lithium and valproic acid and a
      consultation by a second imam, who found no signs of evidence of djinns, was
      successful. We recommend to ask individuals with an Islamic background
      specifically whether djinns might be involved, especially in cases of mental
      problems and unexplained symptoms, and to seek the cooperation of a qualified
      imam or traditional healer for treatment purposes.

PMID- 20132571
TI  - [Airplane crash near Schiphol Airport 25 February 2009: injuries and casualty
      distribution].
AB  - OBJECTIVE: To describe the injuries and distribution of casualties resulting from
      the crash of Turkish Airlines flight TK 1951 near Schiphol Airport on 25 February
      2009. DESIGN: Retrospective, descriptive. METHOD: We reviewed the hospital case
      notes of all casualties of the airplane crash and scored triage at the scene,
      time to emergency department, Abbreviated Injury Scale (AIS) and Injury Severity
      Score (ISS), mortality, length of hospital stay and surgical procedures. RESULTS:
      Of the 135 passengers, 9 died on the scene. A total of 126 survivors were
      examined in 15 hospitals; data from 125 were available for our research. Median
      time between crash and arrival at an Emergency Department was 3.5 hours (range
      1.25-5.5 h). Six passengers were uninjured and 64 were admitted to hospital. A
      total of 297 injuries were registered. Most injuries were to the head and face
      (81), spinal injuries (31) and fractures of extremities (34). In the study group
      17% of the patients had a spinal fracture. The mean ISS was 6.5 (range 1-57). In
      12 patients the ISS was >or= 16. Surgical procedures (80) were necessary in 23
      patients. There was no in-hospital mortality. CONCLUSION: Of the 135 passengers,
      9 died and 120 were injured. Although the accident was in an urban area, there
      was a significant delay between the accident and the arrival of the casualties at
      Emergency Departments. Most of the injuries were to the head and face, and to the
      spine and extremities.

PMID- 20132572
TI  - [GHB withdrawal delirium].
AB  - A 35-year-old man had been using high doses of gamma-hydroxybutyrate (GHB) for
      many years. He had been trying to cut down on use of this drug for 2 months. He
      was admitted to the hospital suffering from a withdrawal delirium accompanied by
      hallucinations and agitation. Use of GHB is increasing in the Netherlands. Along
      with serious intoxication and dependency, the possibility of withdrawal symptoms
      should also be taken into consideration. Administration of high doses of
      benzodiazepines is an effective treatment for these withdrawal symptoms.

PMID- 20132573
TI  - [HIV infection and psychiatric symptoms: a common and important combination].
AB  - About 50% of HIV patients have one or more mental disorders such as depression,
      addiction, anxiety disorders or personality disorders. Two patients, a 58-year
      old male and a 38-year-old female, suffered from HIV infection with comorbid
      mental disorders. The mental disorders interfered with the treatment and outcome
      of their HIV infection. The first patient attempted suicide and was diagnosed
      with severe depression. He had stopped taking his antiretroviral combination
      therapy and had occasionally had unsafe sex. The woman suffered from
      posttraumatic stress disorder, alcohol abuse and depression. She took her
      antiretroviral combination therapy irregularly. Both patients received
      psychiatric treatment. Subsequently, medication adherence improved and the male
      patient no longer had unsafe sexual contacts. For optimal treatment of HIV
      infection it is important that comorbid mental disorders are recognized,
      diagnosed and treated.

PMID- 20132574
TI  - [Measuring intensification of therapy: a new indicator for quality of chronic
      care].
AB  - Research in primary care showed that providers did not routinely respond to
      abnormal values of haemoglobin A1c, blood pressure or LDL cholesterol in patients
      with type 2 diabetes mellitus as defined in clinical practice guidelines. This
      problem is characterised as 'therapeutic inertia'. Providers may be reluctant to
      achieve the goals of therapy for several reasons. Firstly, target values have
      been lowered over time, partly due to influences from the pharmaceutical
      industry. Secondly, the applicability of clinical trial results to patients seen
      in primary care settings is limited. Thirdly, some patients prefer improvement of
      life style above drug therapy. Indicators for therapy intensification could be
      valid and useful for quality improvement if common reasons for non-adherence to
      guidelines are registered in electronic health records.

PMID- 20132575
TI  - [Working together responsibly in primary care--from ideal to reality].
AB  - In January 2010, the Royal Dutch Medical Association (KNMG) will publish the
      guideline 'Sharing responsibilities when cooperating in cure and care'. However,
      in practice the situation is a long way off from the ideal outlined in the
      guideline. The ideal situation for a patient in need of complex care would be to
      have coordination and case management in the hands of one person, but in
      practice, several care providers are involved. The physician has the final
      medical responsibility and should maintain an overview. The care coordinator is
      the person who ensures the other care providers keep to the arrangements made.
      The case manager is the one who has frequent contact with the patient and
      relatives. This requires sound working agreements and adequate, timely exchange
      of information between care providers themselves and between care providers and
      the patient. Working with care plans contributes to this exchange of information
      and should become routine.

PMID- 20132576
TI  - [Guideline on responsible teamwork: don't let it become a manacle].
AB  - The recently published guideline entitled 'Division of responsibility in teamwork
      within the care sector' was developed on the request of the Dutch Health Care
      Inspectorate. Its aim is to ensure that in a teamwork situation in the care
      sector proper agreements are made concerning the responsibilities of the care
      providers who work together. The intention is good, but the execution is open to
      criticism. For instance, there is mention of 'teamwork' as soon as more than one
      caregiver is involved in caring for a patient. The document does not reflect
      everyday practice, but an abstracted theoretical situation, in which the patient,
      nurse and doctor are indicated using terms such as 'subject expert', 'client',
      'care professional' and 'contact'. The document emphasizes responsibilities
      strongly, but the quality of health care could perhaps be better served by the
      motivation of caregivers to provide the best possible care.

PMID- 20132577
TI  - [Diagnostic Image. A woman with abdominal pain].
AB  - A woman had abdominal pain due to ischaemia of the small intestine. This was
      probably caused by torsion due to pandiverticulosis.

PMID- 20132578
TI  - [Hypertrophic cardiomyopathy: DNA diagnosis, genetic counselling and the risk of
      sudden cardiac death].
AB  - Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease with a
      clinical prevalence of 1 in 500. HCM is a monogenetic disease and is inherited
      autosomal dominantly. The disease can manifest itself at any age. Clinical
      presentation varies from symptom-free to severe dyspnoea and sudden cardiac death
      from ventricular arrhythmia. Diagnosis is mainly based on echocardiography and on
      MRI if necessary. In 50-60% of patients, molecular genetic investigation reveals
      a pathogenic mutation in one of the sarcomeric protein genes. The treatment of
      HCM depends on the symptoms and the potential presence of an obstruction in the
      left ventricular outflow tract. The risk of sudden cardiac death must be
      evaluated in order to determine if a prophylactic intracardiac defibrillator is
      necessary. In view of its mendelian form of inheritance, in the Netherlands
      practice guidelines have been issued recently regarding genetic counselling of
      the patient and his or her family and to initiate and coordinate research within
      the family.

PMID- 20132579
TI  - [Quality of the treatment of type 2 diabetes: results from the GIANTT project
      2004-2007].
AB  - OBJECTIVE: To describe the quality of diabetes care at the primary care level
      using the risk factors HbA1c, blood pressure and LDL cholesterol. DESIGN:
      Descriptive cohort study. METHOD: Using data collected electronically from 124
      Dutch general practitioners from the province of Groningen (north Netherlands),
      we assessed the medication treatment level in relation to the level of control
      for HbA1c, blood pressure and LDL cholesterol (adequate, moderate or inadequate
      control). Furthermore, we assessed treatment adjustments between 2004 and 2007 in
      insufficiently controlled patients (HbA1c value, systolic blood pressure or LDL
      cholesterol concentration too high). RESULTS: Data were available for 9646
      patients in 2007. The averages for HbA1c, systolic blood pressure and LDL
      cholesterol were 6.9%, 142 mmHg and 2.3 mmol/l, respectively. Of the patients
      with an HbA1c > 8.5%, 16% were treated with one oral drug and 50% used insulin.
      In 27% of these patients, the treatment was subsequently modified. Between 2004
      and 2007, a slight decrease in average HbA1c was observed, but no changes in
      treatment level. Systolic blood pressure was >or= 140 mmHg in 56% of the
      patients, 19% of whom were not using antihypertensive drugs. Between 2004 and
      2007 the average systolic blood pressure decreased by 6 mmHg, whereas the
      treatment level scarcely increased. Of the 39% of patients whose LDL cholesterol
      level was >or= 2.5 mmol/l, 49% did not use statins. In 2004 there was an increase
      in the percentage of patients using statins. CONCLUSION: The decreasing
      population averages of HbA1c, systolic blood pressure and LDL cholesterol values
      suggest an improvement in the quality of care. However, the relatively few
      therapy modifications observed in insufficiently controlled patients indicates
      that there is still room for improvement.

PMID- 20132580
TI  - Adverse life event reporting and worst illness episodes in unipolar and bipolar
      affective disorders: measuring environmental risk for genetic research.
AB  - BACKGROUND: Studies exploring gene-environment interplay in affective disorders
      now include very large numbers of participants. Methods for evaluating the role
      of adversity in such studies need to be developed that do not rely on lengthy and
      labour-intensive interviews. In the present study, a brief questionnaire method
      for measuring 11 adverse events reported before interview and before their worst
      illness episodes by bipolar, unipolar and healthy control participants,
      participating in genetic association studies, was evaluated. METHOD: Five hundred
      and twelve bipolar disorder (BD) participants, 1447 participants with recurrent
      unipolar depression (UPD) and 1346 psychiatrically healthy control participants
      underwent the researcher-administered version of the List of Threatening
      Experiences Questionnaire (LTE-Q) for the 6 months before their worst affective
      episodes for UPD and BD participants, and for the 6 months before interview for
      the UPD participants and controls. RESULTS: UPD and BD cases were significantly
      more likely to report at least one event, as well as more events in the 6 months
      before interview and before their worst illness episodes, than healthy controls.
      Both manic and depressive episodes were significantly associated with adverse
      events in the BD cases. Depressed mood at the time of interview influenced event
      reporting in UPD and control participants but not the BD cases. Age was
      negatively correlated with the number of events reported by controls.
      CONCLUSIONS: The researcher-administered LTE-Q provides a measure of case-control
      differences for adversity that is applicable in large genetic association
      studies. Confounding factors for event reporting include present mood and age.

PMID- 20132581
TI  - Letter to the editor: Further evidence is required to confirm association between
      CACNA1C gene variants and bipolar affective disorder.

PMID- 20132582
TI  - Neurocognitive functioning before and after the first psychotic episode: does
      psychosis result in cognitive deterioration?
AB  - BACKGROUND: Cognitive impairment is considered to be a core characteristic of
      schizophrenia. The relationship between psychosis and cognitive deterioration,
      however, remains unclear. This longitudinal study investigated the
      neuropsychological functioning of patients before and after their first psychotic
      episode. Cognitive functioning of participants who later developed a psychosis
      was compared to that of people at ultra-high risk (UHR) for psychosis who did not
      develop psychosis at follow-up and healthy controls.MethodParticipants were 41
      persons at UHR for psychosis (the UHR group), of whom 17 developed psychosis
      between the first and second assessment. Seventeen healthy controls were included
      in the study. Cognitive performance was assessed at intake (T0) and again after
      18 months (T1). The areas of cognitive functioning assessed include verbal memory
      and learning, visuospatial working memory, executive function, sustained
      attention and motor speed. RESULTS: The transition group did not perform
      significantly worse at the second assessment than at the first on any of the
      outcome measures. The UHR group performed better on a verbal learning and memory
      test at T1 compared to T0. At T0, the control group scored significantly better
      than the UHR group and the transition group on the verbal learning and memory
      test and the verbal fluency test. CONCLUSIONS: The results indicate that no
      cognitive deterioration occurs during the first psychotic episode. Problems in
      verbal memory may be present before the first episode of psychosis.

PMID- 20132583
TI  - Childhood traumata, Dexamethasone Suppression Test and psychiatric symptoms: a
      trans-diagnostic approach.
AB  - BACKGROUND: Childhood traumatic events and functional abnormalities of the
      hypothalamus-pituitary-adrenal (HPA) axis have been widely reported in
      psychiatric patients, although neither is specific for any diagnosis. Among the
      limited number of studies that have evaluated these topics, none has adopted a
      trans-diagnostic approach. The aim of the present research is to explore the
      relationship between childhood stressors, HPA axis function and psychiatric
      symptoms, independent of the diagnosis. METHOD: A total of 93 moderate to
      severely ill psychiatric out-patients of Florence and Pisa University Psychiatric
      Units and 33 healthy control subjects were recruited. The assessment consisted of
      salivary cortisol pre- and post-low dose (0.5 mg) Dexamethasone, early and recent
      life events, 121 psychiatric symptoms independent of diagnosis, SCID, BPRS.
      RESULTS: In total, 33.5% of patients were Dexamethasone Suppression Test (DST)
      non-suppressors, compared with 6.1% of controls (p=0.001). Among patients, non
      suppression was associated with particular symptoms (i.e. depressive and
      psychotic), but not to any specific diagnosis. Early stressful life events were
      significantly associated with higher salivary cortisol levels, with DST non
      suppression and with approximately the same subset of symptoms. A recent
      stressful event seemed to be associated to the HPA response only in those
      subjects who were exposed to early traumata. CONCLUSIONS: Our report suggests a
      relationship between life stress, HPA axis and psychopathology. A cluster of
      specific psychiatric symptoms seems to be stress related. Moreover, it seems that
      an abnormal HPA response is possibly triggered by an excessive pressure in
      vulnerable individuals.

PMID- 20132584
TI  - Binge eating disorder: a symptom-level investigation of genetic and environmental
      influences on liability.
AB  - BACKGROUND: Recent behavioral genetic studies have emphasized the importance of
      investigating eating disorders at the level of individual symptoms, rather than
      as overall diagnoses. We examined the heritability of binge eating disorder (BED)
      using an item-factor analytic approach, which estimates contributions of additive
      genetic (A), common environmental (C), and unique environmental (E) influences on
      liability to BED as well as individual symptoms. METHOD: Participants were 614
      monozygotic and 410 dizygotic same-sex female twins from the Mid-Atlantic Twin
      Registry who completed a self-report measure of BED symptoms based upon DSM-IV
      criteria. Genetic and environmental contributions to BED liability were assessed
      at the diagnostic and symptom levels, using an item-factor approach. RESULTS:
      Liability to BED was moderately heritable; 45% of the variance was due to A, with
      smaller proportions due to C (13%), and E (42%). Additive genetic effects
      accounted for 29-43% of the variance in individual items, while only 8-14% was
      due to C. CONCLUSIONS: Results highlight the relevance of examining eating
      disorders at the symptom level, rather than focusing on aggregate diagnoses.

PMID- 20132585
TI  - Mathematical modelling of energy expenditure during tissue deposition.
AB  - Predicting the magnitude and rate of weight gain for a given increase of energy
      intake requires a model of whole-body energy expenditure that includes the energy
      cost of tissue deposition. Here, I introduce a mathematical framework for
      modelling energy expenditure that elucidates conceptual problems with the
      classical Kielanowski method for estimating the efficiencies of body fat and
      protein deposition. An alternative approach uses the theoretical biochemical
      efficiencies for protein and fat synthesis in combination with models of energy
      expenditure that include body fat and protein turnover costs. I illustrate this
      alternative approach using a simple mathematical model applied to previously
      published data from growing rats and human infants and compare the simple model
      results with the classical Kielanowski model. While both models fit the data
      reasonably well (R2>0.87 in rats and R2>0.67 in infants), the Kielanowski method
      resulted in parameter estimates that varied widely across experiments, had poor
      precision, and occasionally produced efficiency estimates greater than 1. In
      contrast, the new method provided precise parameter values and revealed
      consistencies across different experiments. The proposed mathematical framework
      has implications for interpreting studies of animal nutrition as well as
      providing a roadmap for future modelling efforts.

PMID- 20132586
TI  - Vitamin A equivalency and apparent absorption of beta-carotene in ileostomy
      subjects using a dual-isotope dilution technique.
AB  - The objective was to quantify the vitamin A equivalency of beta-carotene in two
      diets using a dual-isotope dilution technique and the apparent beta-carotene
      absorption as measured by the oral-faecal balance technique. Seventeen healthy
      adults with an ileostomy completed the 4-week diet-controlled, cross-over
      intervention study. Each subject followed both diets for 2 weeks: a diet
      containing vegetables low in beta-carotene content with supplemental beta
      carotene in salad dressing oil ('oil diet'; mean beta-carotene intake 3.1 mg/d)
      and a diet containing vegetables and fruits high in beta-carotene content ('mixed
      diet'; mean beta-carotene intake 7.6 mg/d). Daily each subject consumed a mean of
      190 microg [13C10]beta-carotene and 195 microg [13C10]retinyl palmitate in oil
      capsules. The vitamin A equivalency of beta-carotene was calculated as the dose
      corrected ratio of [13C5]retinol to [13C10]retinol in serum. Apparent absorption
      of beta-carotene was determined with oral-faecal balance. Isotopic data
      quantified a vitamin A equivalency of [13C10]beta-carotene in oil of 3.6:1 (95 %
      CI 2.8, 4.6) regardless of dietary matrices differences. The apparent absorption
      of (labelled and dietary) beta-carotene from the 'oil diet' (30 %) was 1.9-fold
      higher than from the 'mixed diet' (16 %). This extrinsic labelling technique can
      measure precisely the vitamin A equivalency of beta-carotene in oil capsules, but
      it does not represent the effect of different dietary matrices.

PMID- 20132587
TI  - Experimental infection of selected arthropods with spirurid nematodes Spirocerca
      lupi Railliet & Henry, 1911 and Gongylonema ingluvicola Molin, 1857.
AB  - Gongylonema ingluvicola and Spirocerca lupi are spirurid nematodes that require
      arthropod intermediate hosts in order to complete their life cycle. Beetles of
      the family Scarabaeidae are reported to serve as intermediate hosts for both
      these parasites. In this study selected species of beetles of the family
      Scarabaeidae as well as other groups of arthropods were screened for
      susceptibility to infection with S. lupi and G. ingluvicola. Arthropods were
      exposed to infective eggs of both parasites for a determined period of time and
      dissected/digested to determine the presence or absence of pre-infective and
      infective larvae. All the five species of dung beetles exposed to infection with
      S. lupi, namely, Pachylomerus femoralis, Scarabaeus rugosus, Gymnopleurus
      humanus, Kheper nigroaeneus and Anachalcos convexus were susceptible and, of the
      two species exposed to G. ingluvicola, only Gy. humanus was susceptible.
      Spirocerca lupi eggs developed in millipede species, Daratoagonus cristulatus,
      and remained as encysted larvae, while in Orthoporoides kyrhocephalus no
      development was observed. Spirocerca lupi larvae were not detected in the cricket
      species Gryllus assimilis, or the cockroach species Periplaneta americana, and,
      similarly, G. ingluvicola larvae were not detected in the millipede species O.
      kyrhocephalus. The difference in the susceptibility of the arthropods to the two
      parasite species may depend on their feeding biology.

PMID- 20132588
TI  - Combined apertureless near-field optical second-harmonic generation/atomic force
      microscopy imaging and nanoscale limit of detection.
AB  - A dual function atomic force/near-field scanning optical microscope (AFM/NSOM)
      with an ultrafast laser excitation source was used to investigate apertureless,
      tip enhanced second-harmonic generation (SHG) of ZnO nanowires with spatial
      resolution below the optical diffraction limit. Single-wire SHG spectra show
      little to no contribution from bandgap or other emission. Polarization data
      established values for chi(33)/chi(31) close to previous estimates and confirm
      the SHG process. Experimental results indicate that the SHG signal was reduced
      for nanowires after exposure to an atmosphere of carbon dioxide and water vapor.
      An equation was derived for estimating the minimum chi(2) detectable using
      apertureless SHG NSOM.

PMID- 20132590
TI  - Signal-to-noise contribution of principal component loads in reconstructed near
      infrared Raman tissue spectra.
AB  - The overall quality of Raman spectra in the near-infrared region, where
      biological samples are often studied, has benefited from various improvements to
      optical instrumentation over the past decade. However, obtaining ample spectral
      quality for analysis is still challenging due to device requirements and short
      integration times required for (in vivo) clinical applications of Raman
      spectroscopy. Multivariate analytical methods, such as principal component
      analysis (PCA) and linear discriminant analysis (LDA), are routinely applied to
      Raman spectral datasets to develop classification models. Data compression is
      necessary prior to discriminant analysis to prevent or decrease the degree of
      over-fitting. The logical threshold for the selection of principal components
      (PCs) to be used in discriminant analysis is likely to be at a point before the
      PCs begin to introduce equivalent signal and noise and, hence, include no
      additional value. Assessment of the signal-to-noise ratio (SNR) at a certain peak
      or over a specific spectral region will depend on the sample measured. Therefore,
      the mean SNR over the whole spectral region (SNR(msr)) is determined in the
      original spectrum as well as for spectra reconstructed from an increasing number
      of principal components. This paper introduces a method of assessing the
      influence of signal and noise from individual PC loads and indicates a method of
      selection of PCs for LDA. To evaluate this method, two data sets with different
      SNRs were used. The sets were obtained with the same Raman system and the same
      measurement parameters on bladder tissue collected during white light cystoscopy
      (set A) and fluorescence-guided cystoscopy (set B). This method shows that the
      mean SNR over the spectral range in the original Raman spectra of these two data
      sets is related to the signal and noise contribution of principal component
      loads. The difference in mean SNR over the spectral range can also be appreciated
      since fewer principal components can reliably be used in the low SNR data set
      (set B) compared to the high SNR data set (set A). Despite the fact that no
      definitive threshold could be found, this method may help to determine the cutoff
      for the number of principal components used in discriminant analysis. Future
      analysis of a selection of spectral databases using this technique will allow
      optimum thresholds to be selected for different applications and spectral data
      quality levels.

PMID- 20132593
TI  - The advantages of an attenuated total internal reflection infrared
      microspectroscopic imaging approach for kidney biopsy analysis.
AB  - The benefits of an attenuated total reflection Fourier transform infrared (ATR
      FTIR) imaging approach for kidney biopsy analysis are described. Biopsy sections
      collected from kidney-stone formers are analyzed at the initial stages of stone
      development to provide insights into stone growth and formation. The majority of
      tissue analysis currently conducted with IR microspectroscopy is performed with a
      transflection method. The research presented in this manuscript demonstrates that
      ATR overcomes many of the disadvantages of transflection or transmission
      measurements for tissue analysis including an elimination of spectral artifacts.
      When kidney biopsies with small mineral inclusions are analyzed with a
      transflection approach, specular reflection and the Christiansen effect
      (anomalous dispersion) can occur, leading to spectral artifacts. Another effect
      specific to the analysis of mineral inclusions present in kidney biopsies is
      known as the reststrahlen effect whereby the inclusions become strong reflectors
      near an absorption band. ATR eliminates these effects by immersing the sample in
      a high index medium. Additionally, the focused beam size for ATR is decreased by
      a factor of four when a germanium internal reflection element is used, allowing
      the acquisition of spectra from small mineral inclusions several micrometers in
      diameter. If quantitative analysis of small mineral inclusions is ultimately
      desired, ATR provides the photometrically accurate spectra necessary for
      quantification.

PMID- 20132594
TI  - Fourier transform infrared analysis of the thermal modification of human cornea
      tissue during conductive keratoplasty.
AB  - This paper presents a study using in vitro Fourier transform infrared
      spectroscopy (FT-IR) analysis to determine the thermal damage induced to the
      human cornea by the conductive keratoplasty (CK) procedure. Human cornea tissues
      were treated with CK at different radiofrequency power (58-64%) and pulse
      duration (0.6-1.0 s) settings. The cornea tissues were cryo-sectioned and FT-IR
      analysis was performed to detect the extent of thermal damage by the second
      derivative analysis of the infrared (IR) spectral bands corresponding to protein
      secondary structure. The protein amide I and II spectral bands measured in vitro
      mainly arose from collagen. The denatured cornea tissue showed a higher beta
      sheet content than the native tissue. The extent of the thermal damage created by
      the CK treatment depended on power and duration settings, with the latter having
      a stronger effect. With clinical settings (60%, 0.6 s), the thermal damage area
      was confined within a radius of 100 microm. CK treatment duration had a more
      significant effect on the damage zone than the power setting.

PMID- 20132595
TI  - Improved discrimination between monocotyledonous and dicotyledonous plants for
      weed control based on the blue-green region of ultraviolet-induced fluorescence
      spectra.
AB  - Precision weeding by spot spraying in real time requires sensors to discriminate
      between weeds and crop without contact. Among the optical based solutions, the
      ultraviolet (UV) induced fluorescence of the plants appears as a promising
      alternative. In a first paper, the feasibility of discriminating between corn
      hybrids, monocotyledonous, and dicotyledonous weeds was demonstrated on the basis
      of the complete spectra. Some considerations about the different sources of
      fluorescence oriented the focus to the blue-green fluorescence (BGF) part,
      ignoring the chlorophyll fluorescence that is inherently more variable in time.
      This paper investigates the potential of performing weed/crop discrimination on
      the basis of several large spectral bands in the BGF area. A partial least
      squares discriminant analysis (PLS-DA) was performed on a set of 1908 spectra of
      corn and weed plants over 3 years and various growing conditions. The
      discrimination between monocotyledonous and dicotyledonous plants based on the
      blue-green fluorescence yielded robust models (classification error between 1.3
      and 4.6% for between-year validation). On the basis of the analysis of the PLS-DA
      model, two large bands were chosen in the blue-green fluorescence zone (400-425
      nm and 425-490 nm). A linear discriminant analysis based on the signal from these
      two bands also provided very robust inter-year results (classification error from
      1.5% to 5.2%). The same selection process was applied to discriminate between
      monocotyledonous weeds and maize but yielded no robust models (up to 50% inter
      year error). Further work will be required to solve this problem and provide a
      complete UV fluorescence based sensor for weed-maize discrimination.

PMID- 20132596
TI  - Identification of single fluorescent labels using spectroscopic microscopy.
AB  - Detection of single, fluorescently labeled biomolecules is providing a powerful
      approach to measuring molecular transport, biomolecular interactions, and
      localization in biological systems. Because the biological molecules of interest
      rarely exhibit sufficient intrinsic fluorescence to allow observation of
      individual molecules, they are usually labeled with fluorescent dye molecules,
      fluorescent proteins, semiconductor nanocrystals or quantum dots, or
      fluorescently doped silica or polymer nanospheres to allow their detection.
      Differences in the photophysical and spectral properties of different labels
      allow one to identify individual molecules by distinguishing their corresponding
      labels. A simple approach to measuring fluorescence spectra of individual
      fluorescent labels can be implemented in a standard wide-field fluorescence
      microscope, where a grating or prism is incorporated into the path from the
      microscope to an imaging detector to disperse the emission spectrum. In this
      work, principal components and cluster analysis are applied to the identification
      of fluorescence spectra from single fluorescent labels, with statistical tests of
      the classification results. Spectra are determined from diffracted images of
      fluorescent nanospheres labels, where emission maxima are separated by less than
      20 nm, and of single dye-molecule labels with 30 nm separation. Clusters of
      points in an eigenvector representation of the spectra correctly classify known
      labels (both nanospheres and single molecules) and unambiguously identify unknown
      labels in mixtures.

PMID- 20132597
TI  - Wave-mixing circular dichroism detector for chiral liquid chromatography.
AB  - A circular dichroism (CD) detector based on laser four-wave mixing (FWM) is
      demonstrated using separate injections of analyte enantiomers onto a standard
      silica-based microbore high-performance liquid chromatography (HPLC) column.
      Using the chiral column, a preliminary "detected" mass detection limit of 180 pg
      is determined inside a laser probe volume of 200 pL, corresponding to a circular
      dichroism detection limit, DeltaA, of 2.2 x 10(-5) for (-) camphorquinone.
      Detection sensitivity levels are dramatically improved when our FWM-CD detector
      is interfaced to a microbore system due to the lower mobile-phase flow rates and
      the smaller sample concentrations required for the analysis. Using the microbore
      column, a preliminary circular dichroism detection limit, DeltaA, of 1.6 x 10(-6)
      and a preliminary concentration detection limit of 4.1 x 10(-4) M are determined
      for camphorquinone. This corresponds to a "detected" mass detection limit of 33
      pg for the chiral compound. Laser wave mixing offers better detection limits than
      conventional circular dichroism detection methods and, hence, offers many
      promising applications.

PMID- 20132598
TI  - Temporal and spatial resolution in transmission Raman spectroscopy.
AB  - Picosecond time-resolved transmission Raman data were acquired for 1 mm thick
      powder samples of trans-stilbene, and a Monte Carlo model was developed that can
      successfully model the laser and Raman pulse profiles. Photon migration broadened
      the incident (approximately 1 ps) probe pulse by two orders of magnitude. As
      expected from previous studies of Raman photon migration in backscattering mode,
      the transmitted Raman pulse was broader than the transmitted laser pulse and took
      longer to propagate through the sample. The late-arriving photons followed
      tortuous flight paths in excess of 50 mm on traversing the 1 mm sample. The Monte
      Carlo code was also used to study the spatial resolution (lateral and depth) of
      steady-state transmission Raman spectroscopy in the diffusion regime by examining
      the distribution of Raman generation positions as a function of incident beam
      size, sample thickness, and transport length. It was predicted that the lateral
      resolution should worsen linearly with sample thickness (typically the resolution
      was about 50% of the sample thickness), and this is an inevitable consequence of
      operating in the diffusion regime. The lateral resolution was better at the
      sample surface (essentially determined by the probe beam diameter or the
      collection aperture) than for buried objects, but transmission sampling was shown
      to be biased towards the mid-point of thick samples. Time-resolved transmission
      experiments should improve the lateral resolution by preferentially detecting
      snake photons, subject to constraints of signal-to-noise ratio.

PMID- 20132599
TI  - Determination of ideal offset for spatially offset Raman spectroscopy.
AB  - A key design parameter in spatially offset Raman spectroscopy (SORS) is the
      choice of offset distance between the illumination and collection areas. To
      investigate this choice, we performed SORS measurements on a simple two-layer
      chemical phantom. We show that while the SORS ratio, or the ratio of signal from
      the bottom layer to the top layer, monotonically increases with spatial offset,
      the signal-to-noise ratio (SNR) does not. Specifically, we show that there exists
      a specific spatial offset that yields the best SNR for signal originating in the
      bottom layer of a two-layer sample. We also show that this SNR-optimal offset
      depends upon the strength of the particular Raman band. This work presents the
      considerations that should be taken into account when designing optical probes
      for use in SORS.

PMID- 20132600
TI  - Improving the discriminatory power of a near-infrared microscopy spectral library
      with a support vector machine classifier.
AB  - A multi-group classifier based on the support vector machine (SVM) has been
      developed for use with a library of 48,456 spectra measured by near-infrared
      reflection microscopy (NIRM) on 227 samples representing 26 animal feed
      ingredients and 4 possible contaminants of animal origin. The performance of the
      classifier was assessed by a five-fold cross-validation, dividing at the sample
      level. Although the overall proportion of misclassifications was 27%, almost all
      of these involved the confusion of pairs of similar ingredients of vegetable
      origin. Such confusions are unimportant in the context of the intended use of the
      library, which is the detection of banned ingredients in animal feed. The error
      rate in discrimination between permitted and banned ingredients was just 0.17%.
      The performance of the SVM classifier was substantially better than that of the K
      nearest-neighbors method employed in previous work with the same library, for
      which the comparable error rates are 36% overall and 0.39% for permitted versus
      banned ingredients.

PMID- 20132601
TI  - A graphical method to evaluate spectral preprocessing in multivariate regression
      calibrations: example with Savitzky-Golay filters and partial least squares
      regression.
AB  - In multivariate regression analysis of spectroscopy data, spectral preprocessing
      is often performed to reduce unwanted background information (offsets, sloped
      baselines) or accentuate absorption features in intrinsically overlapping bands.
      These procedures, also known as pretreatments, are commonly smoothing operations
      or derivatives. While such operations are often useful in reducing the number of
      latent variables of the actual decomposition and lowering residual error, they
      also run the risk of misleading the practitioner into accepting calibration
      equations that are poorly adapted to samples outside of the calibration. The
      current study developed a graphical method to examine this effect on partial
      least squares (PLS) regression calibrations of near-infrared (NIR) reflection
      spectra of ground wheat meal with two analytes, protein content and sodium
      dodecyl sulfate sedimentation (SDS) volume (an indicator of the quantity of the
      gluten proteins that contribute to strong doughs). These two properties were
      chosen because of their differing abilities to be modeled by NIR spectroscopy:
      excellent for protein content, fair for SDS sedimentation volume. To further
      demonstrate the potential pitfalls of preprocessing, an artificial component, a
      randomly generated value, was included in PLS regression trials. Savitzky-Golay
      (digital filter) smoothing, first-derivative, and second-derivative preprocess
      functions (5 to 25 centrally symmetric convolution points, derived from quadratic
      polynomials) were applied to PLS calibrations of 1 to 15 factors. The results
      demonstrated the danger of an over reliance on preprocessing when (1) the number
      of samples used in a multivariate calibration is low (<50), (2) the spectral
      response of the analyte is weak, and (3) the goodness of the calibration is based
      on the coefficient of determination (R(2)) rather than a term based on residual
      error. The graphical method has application to the evaluation of other preprocess
      functions and various types of spectroscopy data.

PMID- 20132602
TI  - Multivariate near-infrared reflection spectroscopy strategies for ensuring
      correct labeling at feed bagging in the animal feed industry.
AB  - A key concern in animal feed factories is guaranteeing the correct labeling of
      compound feeds. Therefore, due to incorrect labeling, there is an urgent need for
      new control methods on the claims that can be made. In this study, this question
      has been tackled with different multivariate classification algorithms based on
      the near-infrared spectral fingerprint obtained from a given compound feed
      analyzed in its original physical market presentation form (i.e., cubes, coarse
      meals, pellets). The objective of this paper is the evaluation of different
      methods for establishing a separation among 24 feed types. Two linear methods,
      soft independent modeling of class analogy (SIMCA) and partial least squares
      (PLS) with two approaches to classification (PLSD and PLS-LDA); and one nonlinear
      method, support vector machines (SVM), were studied. The database used had the
      following structure: a first division was made between granules and meals; within
      these two groups, there was a second division according to three animal species
      to which the feed was marketed (bovine, ovine, and porcine); within each species
      there was a third division according to the age or physiological status of the
      animal (i.e., lactating dairy cattle, starters, etc.). Given the database
      structure, all the methods were evaluated following two strategies: (1)
      development of a model composed of the nine classification models corresponding
      to the structure of the data; and (2) development of a unique model that
      discriminates among the 24 classes of different feeds. With both strategies the
      lowest percentage of misclassified samples was achieved with the SVM method
      (3.96% with strategy 1 and 2.31% with strategy 2). Among the linear methods
      evaluated, SIMCA yielded the best results, with a percentage of 8.47%
      misclassified samples with strategy 1 and 4.05% misclassified samples with
      strategy 2. The results in this study show the ability of near-infrared
      spectroscopy to make acceptable classifications of feed types based only on
      spectral information, with differences in performance depending on the
      multivariate algorithm used.

PMID- 20132603
TI  - Feasibility of near-infrared spectroscopy for on-line grading of sawn lumber.
AB  - Near-infrared (NIR) spectroscopy, coupled with multivariate analysis, has been
      used to evaluate the wood properties of sawn lumber of Japanese larch (Larix
      kaempferi), whose diffuse reflection spectra were acquired under static and
      moving conditions. Prediction models of the dynamic modulus of elasticity
      (E(fr)), the modulus of elasticity in bending tests (E(b)), the bending strength
      (F(b)), the wood density (DEN), and the moisture content (MC) were developed
      using partial least squares (PLS) analysis. For all wood properties, models
      obtained from data collected under the moving condition as an analogue of on-line
      measurement were superior to those from the static condition data. The regression
      coefficients for the PLS models predicting the mechanical properties in both
      static and moving conditions showed clear peaks at the absorption bands due to
      the three major polymers of wood, i.e., cellulose, hemicellulose, and lignin. NIR
      spectroscopy has high potential for the on-line grading of sawn lumber.

PMID- 20132604
TI  - Detection of citrus Huanglongbing by Fourier transform infrared-attenuated total
      reflection spectroscopy.
AB  - Citrus Huanglongbing (HLB, also known as citrus greening disease) was discovered
      in Florida in 2005 and is spreading rapidly amongst the citrus growing regions of
      the state. Detection via visual symptoms of the disease is not a long-term viable
      option. New techniques are being developed to test for the disease in its earlier
      presymptomatic stages. Fourier transform infrared-attenuated total reflection (FT
      IR-ATR) spectroscopy is a candidate for rapid, inexpensive, early detection of
      the disease. The mid-infrared region of the spectrum reveals dramatic changes
      that take place in the infected leaves when compared to healthy non-infected
      leaves. The carbohydrates that give rise to peaks in the 900-1180 cm(-1) range
      are reliable in distinguishing leaves from infected plants versus non-infected
      plants. A model based on chemometrics was developed using the spectra from 179
      plants of known disease status. This model then correctly predicted the status of
      >95% of the plants tested.

PMID- 20132605
TI  - Spectroscopic evidence of the mechanism involved in the cationic diglycidyl ether
      of bisphenol A curing with rare earth metal triflates.
AB  - The cross-linking of diglycidyl ether of bisphenol A (DGEBA) using three rare
      earth triflates as initiators (lanthanum, ytterbium, and scandium) was studied by
      in situ Fourier transform infrared (FT-IR) spectroscopy. Cationic ring opening of
      epoxides can proceed through two different mechanisms: activated monomer (AM) and
      active chain end (ACE). Using advanced chemometric methods such as perturbation
      correlation moving-window two dimensional correlation spectroscopy (PCMW2D) and
      multivariate curve resolution-alternating least squares (MCR-ALS) it has been
      possible to obtain spectroscopic evidence of the two mechanisms. Traditionally,
      the demonstration of different mechanism pathways requires designing specific
      experiments. The novelty of the present study is to find, without a specific
      experimental design, spectroscopic evidence of the pathway of the polymerization
      process and to analyze the effect of these initiators, as well as the evolution
      of the species that takes part in the curing process by structural techniques
      such as attenuated total reflection (ATR) FT-IR.

PMID- 20132606
TI  - Infrared spectroscopy of ionic liquids: quantitative aspects and determination of
      optical constants.
AB  - The infrared (IR) spectra of ionic liquids involving 1-butyl-3-methylimidazolium
      (BMI) and the (CF(3)SO(2))(2)N(-), BF(4)(-), or PF(6)(-) anions, recorded in the
      transmission and attenuated total reflection (ATR) modes, exhibit strong
      differences in the most intense anion absorption profiles. These distortions come
      from optical effects and make difficult any quantitative analysis of, for
      example, the antisymmetric stretching vibrations of the BF(4)(-) and PF(6)(-)
      anions. A method is proposed to determine the optical constants, from which any
      type of experimental spectrum can be simulated. It is then possible to use the
      anion vibrational bands as spectroscopic probes of the local interactions
      occurring in the neat ionic liquids and in solutions. This is illustrated by a
      direct identification of ion pairs and separated ions in the IR spectra of BMI
      PF(6) solutions.

PMID- 20132607
TI  - Phonon response in the infrared region to thickness of oxide films formed by
      atomic layer deposition.
AB  - Experimental transmission infrared spectra of gamma-Al(2)O(3) and ZnO films are
      collected from heat-treated thin oxide films deposited with uniform thickness on
      Si(100) using atomic layer deposition. We show that the Berreman thickness, i.e.
      the upper limit for a linear relationship between oxide film thickness and phonon
      absorbance in the infrared region in transmission configuration, is a concept
      that applies to both transverse and longitudinal optical phonons. We find that
      for aluminum oxide films the Berreman thickness is 125 nm, and we estimate that
      it is around approximately 435 nm for zinc oxide films. Combining experiment and
      simulation, we also show that the Berreman thickness is the maximum distance
      allowed between interfaces for Snell's law and Fresnel's formulas to determine
      the optical properties in the infrared region and in transmission configuration
      for a layer system including an oxide film. Below the Berreman thickness, a
      Taylor series expansion of the absorbance coefficient determines the linear
      relationship between phonon absorbance and oxide film thickness t, so that as t -
      > 0 absorption A(p) is proportional to 4pi omega(ph)t, where omega(ph) indicates
      optical phonon frequency. Above the Berreman thickness, field boundary conditions
      at the air/oxide film interface effectively contribute with a single interface in
      explaining optical phonon absorbance. Preliminary infrared spectra in reflection
      configuration for gamma-Al(2)O(3)/Si(100) are discussed, and the obtained data
      support the conclusions reported for the transmission configuration.

PMID- 20132608
TI  - Wiener bounds for complex permittivity in terahertz spectroscopy: case study of
      two-phase pharmaceutical tablets.
AB  - The terahertz measurement technique has become popular in the field of
      pharmaceutical technology for tablet quality inspection. Spectral data obtained
      from the tablets is based on the utilization of Fresnel's formulas for an ideal
      slab. However, a tablet is a porous medium. Hence, in the THz gap one has to
      assume that a tablet constitutes at least an effective medium if the Fresnel
      theory is applied in quantitative permittivity spectra analysis. Hence, it is
      suggested that one should consider instead of the permittivity of homogeneous
      media the concept of effective permittivity in the THz terminology of porous
      tablets. Usually the fill factor of a component of a tablet is known but not the
      detailed bulk structure. Nevertheless, it is possible to estimate the complex
      effective permittivity of a tablet with the aid of so-called Wiener bounds. The
      idea of this article is to present a modification of Wiener bounds applied to the
      estimation of the real and imaginary part of the permittivity of the pure
      component of a tablet. As an example, the effective complex permittivity of a
      starch acetate tablet is considered.

PMID- 20132609
TI  - Drug supply shortages in 2010: the inexcusable failure of global tuberculosis
      control.

PMID- 20132610
TI  - Drug-resistant tuberculosis: reality and potential threat.

PMID- 20132611
TI  - Evidence-based prevention of MDR-TB: an intervention whose time has come.

PMID- 20132612
TI  - Ad fontes!

PMID- 20132613
TI  - Impact of antiretroviral therapy on tuberculosis risk in different TB-HIV
      epidemics.

PMID- 20132614
TI  - Could oral hypoglycemics be the new therapeutic answer to chronic obstructive
      pulmonary disease?

PMID- 20132615
TI  - Lessons on lung diseases in 2009.

PMID- 20132616
TI  - Global policies and practices for managing persons exposed to multidrug-resistant
      tuberculosis.
AB  - SETTING: In the 1960s, treatment for latent tuberculosis infection (LTBI) with
      isoniazid proved to be so effective, safe, and inexpensive that research into
      alternative treatments virtually ceased. Now that multidrug-resistant
      tuberculosis (MDR-TB) is widespread, no data are available to guide the
      management of persons exposed to MDR-TB (contacts). METHODS: We surveyed National
      TB Program directors and MDR-TB program managers about current practices for
      managing MDR-TB contacts in countries with an MDR-TB prevalence of >2% in new
      patients and those with programs for managing MDR-TB. RESULTS: Of 35 countries
      that met the survey criteria, 25 (71%) responded; 24 of these (96%) have a
      guideline for managing TB contacts. Of these, 19 (76%) usually or always
      evaluated contacts and treated LTBI. In contrast, 10 (40%) countries reported
      having a guideline for managing MDR-TB contacts, 11 (44%) usually or always
      evaluated MDR-TB contacts, and 9 (36%) treated LTBI. Only two (8%) used a regimen
      that has activity against MDR-TB. Lack of evidence or guidelines was the main
      reason for not treating MDR-TB contacts. CONCLUSIONS: Management of MDR-TB
      contacts is inconsistent and ineffective due to lack of evidence-based
      guidelines. There is an urgent need to generate evidence to guide policy.

PMID- 20132617
TI  - Adverse events related to multidrug-resistant tuberculosis treatment, Latvia,
      2000-2004.
AB  - SETTING: Latvia has one of the highest rates of multidrug-resistant tuberculosis
      (MDR-TB) globally. Clinical management of MDR-TB requires lengthy multidrug
      regimens that often cause adverse events. DESIGN: We retrospectively reviewed
      records of patients who began MDR-TB treatment between 2000 and 2004. Treatment
      related adverse events and factors associated with experiencing adverse events
      were evaluated. We also examined the frequency of and reasons for changing drug
      regimens. RESULTS: Among 1027 cases, 807 (79%) experienced at least one adverse
      event, with a median of three events per case. The most commonly reported events
      were nausea (58%), vomiting (39%) and abdominal pain (24%). More serious events,
      such as psychiatric episodes (13%), hepatitis (9%) and renal failure (4%), were
      relatively frequent. A change in drug dose due to an adverse event occurred in
      201 (20%) cases, while 661 (64%) had at least one drug discontinued temporarily
      or permanently. Being older, female, having bilateral lung cavities and a greater
      number of TB symptoms at baseline were associated with an increased number of
      events. CONCLUSION: Adverse events were prevalent among MDR-TB cases treated in
      Latvia, with over two thirds requiring discontinuation of at least one drug. MDR
      TB patients who are female, older or have severe TB disease should be closely
      monitored for treatment-related adverse events.

PMID- 20132618
TI  - Determination of critical concentrations of second-line anti-tuberculosis drugs
      with clinical and microbiological relevance.
AB  - BACKGROUND: Reliable DST against second-line anti-tuberculosis drugs (SLDs) is
      crucial for the management of the increasing burden of patients affected by
      multidrug- and extensively drug-resistant TB. METHODS: This study utilizes 252
      clinical isolates of Mycobacterium tuberculosis from five countries (Hong Kong
      Special Administrative Region, Korea, Latvia, Peru, Philippines) with documented
      treatment histories to establish clinically and microbiologically relevant
      critical concentrations (CCs) of six SLDs for three routine testing methods: the
      absolute concentration method using Lowenstein-Jensen (LJ) medium, the 1%
      proportion method using Middlebrook 7H10 agar medium, and the radiometric BACTEC
      460 system. FINDINGS: In LJ medium, CCs of capreomycin, ethionamide, kanamycin,
      ofloxacin, rho-aminosalicylic acid and cycloserine (CS) were respectively 40.0,
      40.0, 30.0, 3.0, 1.0 and 30.0 mg/l. In 7H10 agar medium, the respective CCs for
      the first five antibiotics (except CS) were 8.0, 2.0-3.0, 3.0-5.0, 1.0-1.5 and
      0.5-1.0 mg/l. In BACTEC 460 broth, the respective CCs were 1.5-2.0, 1.0-1.5, 2.0
      3.0, 0.5-1.0 and 0.5-1.0 mg/l. Precautions in DST interpretation was also
      discussed. INTERPRETATION: By adopting this set of CCs as a global standard to
      define second-line drug susceptibility and resistance, as well as precautions in
      result interpretation, the screening, diagnosis and management of patients with
      drug-resistant TB can be greatly improved.

PMID- 20132619
TI  - Decrease in risk of tuberculosis infection despite increase in tuberculosis among
      young adults in urban Vietnam.
AB  - OBJECTIVE: To assess whether the increase in tuberculosis (TB) notification rates
      among young adults in Vietnam reflects increased transmission in the population
      at large. METHOD: Trends of case notification rates of new smear-positive TB were
      calculated from routinely reported data of district TB units over the period 1996
      2005. Results from repeated tuberculin surveys among children aged 6-9 years were
      obtained to calculate the trend in annual risk of TB infection (ARTI). FINDINGS:
      From 1996 to 2006, notification rates in the age group 15-24 years increased by
      4.3% per year, and more so in highly urbanised (6.7%) than in rural districts
      (1.7%). The ARTI in urban districts declined from 2.4% in 1992 to 1.2% in 1998
      and 0.9% in 2005. In rural districts, the ARTI increased from 0.7% in 1991 to
      1.2% in 1997, and then declined to 0.9% in 2006. CONCLUSION: The increase in TB
      notification rates among young adults in Ho Chi Minh Province is accompanied by a
      decrease in ARTI in children. This suggests that the trend in TB notification
      among young adults reflects increased rates of progression from infection to
      disease and/or increased transmission within this age group, rather than
      increased transmission in the population at large.

PMID- 20132620
TI  - Health status of UK patients with active tuberculosis.
AB  - OBJECTIVE: To assess the impact of tuberculosis (TB) and its treatment on
      patients' health status. METHODS: Questionnaires were administered prospectively
      to patients at three clinics in London at diagnosis and 2 months into therapy. We
      assessed generic health-related quality of life (Short Form 36 [SF-36] and EQ-5D)
      and psychological burden (State-Trait Anxiety Short-Form, Center for
      Epidemiologic Studies Depression Scale, worry items). RESULTS: Of the 61
      participants (response rate 94%), 89% were non-UK born, 67% had pulmonary TB and
      38% were aged 30-45 years. At diagnosis, scores for all eight SF-36 dimensions
      were significantly worse than UK general population norm scores. At follow-up,
      scores had improved significantly (P < 0.01), except for physical functioning and
      general health perception, but remained below the UK norm, except for vitality
      and mental health. Respondents' mean anxiety and depression scores were high at
      diagnosis (48 and 22, respectively), and anxiety scores remained high at follow
      up. Worries most frequently reported concerned patients' own health (92%) and
      that of their family (82%). CONCLUSIONS: TB patients suffer from significantly
      diminished health-related quality of life at diagnosis. Although treatment
      significantly improved patients' health status within 2 months, scores for many
      domains remain below UK norm scores. This emphasises the importance of a holistic
      approach to care and should inform the evaluation of future interventions.

PMID- 20132621
TI  - Knowledge, attitudes and practices regarding tuberculosis in two districts of
      Punjab, Pakistan.
AB  - SETTING: Pakistan ranks eighth among the world's highest tuberculosis (TB) burden
      countries, and Punjab province accounts for 60% of TB cases nationally.
      OBJECTIVE: To explore knowledge, attitudes and practices regarding TB in the
      general population of two districts of Punjab province, and the effect of socio
      economic determinants. DESIGN: In a cross-sectional survey, subjects aged > or
      =20 years were randomly selected using multistage cluster sampling and
      interviewed. A knowledge score was formulated based on nine questions. Bivariate
      analysis using the chi(2) test was employed to independently correlate socio
      economic factors with understanding of disease and information sources.
      Attitudes, practices and information sources were also compared with TB
      knowledge. RESULTS: Forty-two per cent of the surveyed population had good
      knowledge about TB, which was associated with better education, high income and
      good housing (all P < 0.001). Despite the fact that the majority (82.2%) knew
      about correct treatment, less than half (48.8%) were aware that diagnosis and
      treatment were free. Intended health-seeking behaviour was determined by better
      education (P = 0.011), good housing (P = 0.004) and good knowledge about TB (P <
      0.001). Television (69.4%) and health workers (43.6%) were the main sources of
      information. CONCLUSION: Socio-economic factors should be considered when
      designing communication strategies and prioritising TB prevention and control
      interventions.

PMID- 20132622
TI  - Effect on tuberculosis outcomes of educational outreach to South African clinics
      during two randomised trials.
AB  - SETTING: Public sector primary care clinics in Free State Province, South Africa.
      OBJECTIVES: To investigate the effects of on-site in-service clinical skills
      training for nurse practitioners on tuberculosis (TB) treatment outcomes in the
      same clinics. DESIGN: Analysis of TB programme data from clinics taking part in
      two consecutive randomised trials of educational outreach aimed at improving
      respiratory and human immunodeficiency virus/acquired immune-deficiency syndrome
      care based on the Practical Approach to Lung Health. We compared treatment
      outcomes between control and intervention clinics among all patients diagnosed
      with TB during either trial. RESULTS: During the two trials, participating
      clinics treated 4187 and 2333 TB patients, respectively. Neither intervention was
      associated with better outcomes overall. However, among retreatment patients,
      cure or completion rates in intervention clinics were significantly higher during
      the second trial (OR 1.78, 95%CI 1.13-2.76). Patients in clinics that had
      received both interventions had higher cure or completion rates (OR 1.99, 95%CI
      1.53-2.58) and lower default rates (OR 0.25, 95%CI 0.097-0.63) than patients in
      clinics that had received neither intervention. CONCLUSION: Although not
      primarily focused on TB treatment, the interventions appeared to improve
      successful treatment completion rates among TB retreatment cases. Integrated care
      programmes support attainment of important TB programme goals.

PMID- 20132623
TI  - Incidence of tuberculosis after HAART initiation in a cohort of HIV-positive
      patients in Burkina Faso.
AB  - OBJECTIVE: To determine the incidence rates of tuberculosis (TB) after the
      initiation of highly active antiretroviral treatment (HAART). METHODS: We
      conducted a retrospective cohort study on four human immunodeficiency virus (HIV)
      treatment centres in Ouagadougou, Burkina Faso. TB incidence was measured at
      different intervals after HAART initiation. Cox regression models were used to
      identify factors associated with TB incidence. RESULTS: We analysed a cohort of
      2383 subjects with a mean follow-up period of 836 days (standard deviation +/-
      443.4). TB incidence rate was highest during the first trimester of HAART; after
      3 months of treatment, the total TB case incidence dropped by 60% from 5.77/100
      person-years (py) to 2.23/100 py. World Health Organization clinical Stage III or
      IV, CD4+ T-cell count < 50 cells/microl and body mass index (BMI) < 18.5 were
      associated with increased risk of TB on univariate analysis. In the Cox
      regression, BMI < 18.5 and CD4+ T-cell count < 50 cells/microl at HAART
      initiation were independently associated with a two-fold higher risk of TB.
      CONCLUSIONS: Delaying HAART initiation until the CD4+ T-cell count drops to <50
      cells/microl significantly increases TB incidence in the first 3 months after
      HAART initiation. Active case finding for TB is an essential element of standard
      clinical care in HIV-positive patients during the initial period of HAART.

PMID- 20132624
TI  - Association of chest radiographic abnormalities with tuberculosis disease in
      asymptomatic HIV-infected adults.
AB  - SETTING: Francistown and Gaborone, Botswana. OBJECTIVE: Chest radiography is used
      to screen for tuberculosis (TB) in asymptomatic persons living with the human
      immunodeficiency virus (PLWH) seeking isoniazid preventive therapy (IPT). We
      describe radiographic features in PLWH in a TB-endemic setting and identify
      features associated with TB disease. DESIGN: Asymptomatic PLWH seeking IPT under
      program conditions for a clinical trial between 2004 and 2006 received chest
      radiographs (CXRs) that were read using the standardized Chest Radiograph Reading
      and Recording System (CRRS). Clinical characteristics, including TB disease, were
      compared with the radiographic findings. RESULTS: From 2732 screening CXRs, 183
      had one or more abnormalities and were scored using CRRS, with 42% having
      infiltrates (36% upper lobes), 35% parenchymal fibrosis and 32% adenopathy. TB
      disease status was determined in 129 (70%) PLWH, of whom 22 (17%) had TB disease.
      TB disease was associated with upper lobe infiltrates (relative risk [RR] 3.0,
      95%CI 1.5-6.2) and mediastinal adenopathy (RR 3.9, 95%CI 1.8-8.4). The
      sensitivity and specificity of either upper lobe infiltrates or mediastinal
      lymphadenopathy for TB disease were respectively 64% and 82%. CONCLUSION: A
      combination of CXR features was useful for predicting TB disease in asymptomatic
      PLWH. CRRS should be used more frequently in similar studies.

PMID- 20132625
TI  - Can hepatitis B virus infection predict tuberculosis treatment liver toxicity?
      Development of a preliminary prediction rule.
AB  - BACKGROUND: Liver toxicity due to tuberculosis (TB) treatment is a frequent cause
      of treatment interruption, and may sometimes lead to a change in therapy to a
      less potent regimen. OBJECTIVE: To estimate the risk of hepatotoxicity in
      patients with or without hepatitis B virus (HBV) infection receiving TB treatment
      and to develop a clinical prediction rule. DESIGN: A prospective observational
      follow-up was conducted. Data from 154 patients who underwent TB treatment were
      analysed. Crude risk ratios were estimated and a Cox proportional hazards model
      was fit. RESULTS: The mean follow-up time was 187 days. Crude risk ratios showed
      that ethnicity, human immunodeficiency virus infection, multiple sexual partners,
      highly active antiretroviral treatment, and clinical forms of TB were possible
      predictors of liver toxicity. HBV infection and other sexually transmitted
      diseases showed considerable relative risk, although not statistically
      significant. The Cox proportional hazards model identified the following
      predictors of hepatotoxicity: White ethnicity, multiple sexual partners, high
      baseline alanine transferase and clinical forms of TB. Active HBV, indicated by
      the detection of surface antigen HBV, could predict hepatotoxicity, although with
      low precision. CONCLUSION: Using this information, we were able to apply a score
      and draw a nomogram to estimate survival probabilities and median times to event
      for each patient.

PMID- 20132626
TI  - Rapid diagnosis in early stage renal tuberculosis by real-time polymerase chain
      reaction on renal biopsy specimens.
AB  - OBJECTIVE: To determine the early rapid diagnosis of renal tuberculosis (RTB) by
      real-time polymerase chain reaction (PCR) on renal biopsy specimens. METHODS:
      Ninety patients were selected for this study. The patients were divided into the
      following three groups: RTB, non-RTB (N-RTB) and clinically suspected RTB (CS
      RTB). The renal biopsy specimens of these patients were used for Mycobacterium
      tuberculosis DNA detection by real-time PCR, using 35 and 40 as cycle threshold
      (C(T)) cut-off values. Morning urine samples were collected for M. tuberculosis
      culture. RESULTS: In the RTB group, 25 C(T)35 and 28 C(T)40 patients were PCR
      positive, seven of whom were urine M. tuberculosis culture-positive. In the N-RTB
      group, four C(T)35 and 13 C(T)40 patients were PCR-positive, none of whom were
      urine M. tuberculosis culture-positive. In the CS-RTB group, nine C(T)35 and 14
      C(T)40 patients were PCR-positive, two of whom were urine M. tuberculosis culture
      positive during 12 months of follow-up. The sensitivity and specificity of real
      time PCR (C(T)40) were respectively 93.3% and 56.7%. The sensitivity and
      specificity of real-time PCR (C(T)35) were respectively 83.3% and 86.7%. The
      sensitivity and specificity of the urine M. tuberculosis culture were
      respectively 23.3% and 100%. CONCLUSIONS: The detection of M. tuberculosis DNA in
      renal biopsy tissue by real-time PCR is highly sensitive. Real-time PCR can
      increase diagnostic accuracy and provide valuable information regarding the early
      diagnosis of RTB.

PMID- 20132627
TI  - Effector memory T-cells dominate immune responses in tuberculosis treatment:
      antigen or bacteria persistence?
AB  - OBJECTIVE: To compare ex vivo immunological responses upon stimulation of
      lymphocytes with Mycobacterium tuberculosis-specific antigens in three groups: 1)
      subjects diagnosed with tuberculosis (TB) in the early 1940s and 1950s but who
      did not receive anti-tuberculosis chemotherapy (n = 5), 2) subjects treated with
      anti-tuberculosis agents prior to the rifampicin (RMP) era (n = 26) and 3)
      subjects who received RMP as a part of modern combination therapy (n = 7).
      DESIGN: A total of 38 healthy subjects, mean age 70 +/- 13 years, with a history
      of previously treated TB were recruited. Peripheral blood mononuclear cells were
      collected and analysed as a batch by ELISpot. Representative samples with high
      reactivities were further immunophenotypically characterised. RESULTS: No
      differences between the studied groups were detected with regard to the
      frequencies of reactive lymphocytes. The dominant immunophenotypic profile of the
      representative responders, irrespective of the treatment schemes, was
      CD4+CD45RO+CD45RA-CD27-CD28-CCR7-, compatible with the fast reacting effector
      memory T-cell lineage (T(EM)). CONCLUSION: Specific T(EM) cells persist even in
      subjects treated for TB decades ago with modern anti-tuberculosis chemotherapy.
      Additional studies are needed to address the question of what drives the survival
      of T(EM) after adequate treatment: persistence of antigens or bacteria.

PMID- 20132628
TI  - Graphic tobacco health warnings: which genre to choose?
AB  - BACKGROUND: Tobacco prevention studies show that graphic health warnings are more
      effective than text warnings, but there are no data on the effectiveness of
      different types of graphic health warnings in a Pakistani population. Even
      marginal differences in the effectiveness of genres can be of potential
      significance for public health. OBJECTIVE: To study the effectiveness of
      different types of graphic tobacco warnings in a Pakistani population. STUDY
      DESIGN: We presented ten anti-smoking warnings to randomly selected volunteers (n
      = 170) and recorded their opinion on the effectiveness of each warning. The
      warnings were based on a range of images aimed at the diverse population
      interviewed. A grading scale based on appeal, application, educational potential
      and motivation towards cessation was used to produce a composite grade of
      perceived effectiveness of the warning. RESULTS: Our results indicate that
      graphic warnings reach a greater proportion of the population than text warnings.
      Those appealing to logic, and those inculcating a sense of fear by showing a
      deleterious outcome of smoking, were judged likely to be most effective in
      motivating smokers to quit and preventing experimental smokers from forming a
      habit.

PMID- 20132629
TI  - The impact of insulin sensitisers on lung function in patients with chronic
      obstructive pulmonary disease and diabetes.
AB  - SETTING: It has been reported that diabetes mellitus (DM) is associated with poor
      pulmonary function, which could be explained by insulin resistance. OBJECTIVE: To
      evaluate whether insulin sensitisers (ISs) have beneficial effects on lung
      function in patients with chronic obstructive pulmonary disease (COPD) and DM.
      DESIGN: This retrospective study included patients with both COPD and DM who
      attended Seoul National University Hospital for treatment between 1 January 2000
      and 31 August 2007. They were treated with inhalers for COPD and oral
      hypoglycaemia agents, including ISs or insulin, for DM. The primary outcome was a
      change in lung function in spirometric examinations. RESULTS: Among 61 patients
      enrolled, 32 were in the no IS group, while 29 were in the IS group. On
      multivariable regression analysis, the IS group showed a significantly greater
      change in forced vital capacity (FVC) than the no IS group (adjusted beta
      coefficient 131.9, 95%CI 8.5-255.4, P = 0.04). CONCLUSIONS: Treatment with an IS
      was independently associated with improvements in FVC in patients with both COPD
      and DM, compared with treatment without IS.

PMID- 20132630
TI  - Prevalence of pulmonary tuberculosis among the Bharia, a primitive tribe of
      Madhya Pradesh, central India.
AB  - A cross-sectional survey was undertaken to estimate the prevalence of pulmonary
      tuberculosis (TB) among the primitive Bharia tribe of Madhya Pradesh, India.
      Virtually the entire community in Patalkot valley of Chhindwara District was
      covered. Individuals aged > or =15 years were questioned about chest symptoms
      relating to TB. Sputum samples were collected and examined by smear microscopy
      and culture. The overall prevalence of pulmonary TB was found to be 432 per 100
      000 population-not dissimilar to that seen in the wider population in India.
      There is, however, an urgent need to strengthen TB services in the area to
      improve access for this group.

PMID- 20132631
TI  - Evaluation of an international training course to build programmatic capacity for
      tuberculosis control.
AB  - We evaluated the international training course of the Research Institute of
      Tuberculosis, Kiyose, Japan, by e-mailing structured questionnaires to
      participants who attended the course from 2001 to 2007. Of 62 responding
      participants, 34 developed action plan projects (APPs) and 28 developed
      operations research projects (ORPs). Among respondents drafting APPs, 27 (79%)
      started implementing projects, and 24 (88%) completed over half of their planned
      activities. Among respondents drafting ORPs, 11 (39%) started projects but no
      scientific papers were published. The main reasons for the failure to implement
      ORPs were due to lack of time, funds, and disapproval by supervisors. A
      sequential training model may better address barriers to teaching and assisting
      ORPs.

PMID- 20132632
TI  - Pharmacokinetics of isoniazid in moderately malnourished children with
      tuberculosis.
AB  - Severe malnutrition is known to affect the pharmacokinetics of isoniazid (INH) in
      children. However, the effect of moderate malnutrition, which may be more
      prevalent, is not known. INH was administered to 20 children with tuberculosis at
      a single dose of 5 mg/kg, and serial blood samples were collected. The serum INH
      concentrations were higher in the undernourished group but the pharmacokinetic
      parameters were comparable with those in the normal nutrition group. Weight gain
      was significantly more in the undernourished group after 1 month of treatment.
      The study suggests that INH pharmacokinetics may not be significantly altered in
      children with moderate malnutrition.

PMID- 20132633
TI  - Misleading conclusion.

PMID- 20132635
TI  - Online learning in primary care: the importance of e-professionalism.

PMID- 20132636
TI  - Preparing the practice for an education QA visit.

PMID- 20132637
TI  - Do visits help improve the quality of teaching within undergraduate teaching
      practices?
AB  - The Academic Unit of Primary Care (AUPC) at the University of Leeds is
      responsible for the quality assurance of 79 teaching practices, who contribute
      14% of the MBChB clinical placements. We wanted to analyse the effects of
      visiting undergraduate teaching practices as part of an approach to quality
      assurance. A survey of 79 practices in Yorkshire revealed a high level of tutor
      satisfaction with the process and 41% showed evidence of change following the
      visit. Some qualitative information was elicited from the survey and is used to
      illustrate examples of change. Our paper looks at the role of practice visits as
      part of a system of quality assurance and makes further recommendations to
      improve their focus and effectiveness. The paper is timely given the large
      increase in primary care placements and the recent discussions about the
      development of quality criteria for undergraduate medical teaching in the
      community.

PMID- 20132638
TI  - Describing the learning climate of general practice training: the learner's
      perspective.
AB  - The learning climate is an important aspect of educational environments that
      impacts on learner satisfaction, stress and attitudes to learning. Quality
      management of educational environments has traditionally focused on teacher
      development and aspects of the environment that are easily quantifiable. This
      study describes the learning climate of GP training practices from the
      perspective of the learners. The information can be used to inform a learner
      centred and evidence-based system of quality management. Further development of
      the themes could produce a quantitative tool, to provide data on the learning
      climate of GP training practices. This could assist in the quality management of
      GP training in the UK.

PMID- 20132639
TI  - Digital storytelling for reflection in undergraduate medical education: a pilot
      study.

PMID- 20132640
TI  - The formative impact of general practice appraisals: a post-appraisal
      questionnaire survey.
AB  - Since their national implementation in 2002, GP appraisals are being extensively
      applied. There is a positive link between appraisals and patient care in
      hospitals. There also appears to be no uniform model for appraisals, which has
      led to confusion between their 'stand-alone' role as a formative assessment tool
      and their contribution to summative revalidation. This is a case study into the
      formative element of appraisals as carried out at a primary care trust in Wessex.
      We offer an insight into the diversity of learning outcomes and developmental
      potential of the formative element of appraisals (excluding revalidation)
      attained through the analysis of emerging themes from responses to a purposely
      designed questionnaire aimed at appraisees (questions appear in the tables). To
      our knowledge this is one of the few research articles that deal with the
      formative educational element of GP appraisals.

PMID- 20132641
TI  - The Foundation Programme in general practice: the value added of the attachment -
      a Wessex experience.
AB  - The general practice (GP) educational arena offers a range of learning
      opportunities for junior doctors in the Foundation Programme (FP). In this study
      we explored what might be the value added of the experience in GP for current FP
      trainees in their second year of training (F2s) in Wessex. This is particularly
      important in view of the changes introduced by the new form of training which
      include a competence-based curriculum, new assessment forms, and shorter length
      of training than previously experienced by GP trainers in Wessex (four months).
      The aim of our study was therefore to explore what might be the contribution of
      the GP attachment to the formation of FP doctors in Wessex. We collected data
      from trainers and trainees on their perspectives of the GP attachment using two
      distinct qualitative questionnaires. We show that trainees in Wessex benefit from
      the experience in a variety of ways. Variations on the learning opportunities
      offered in GP may depend on the location of the practice, social environment,
      cases reviewed, teaching styles, perceptions on the new curriculum and
      assessment, and the general management of the practice.

PMID- 20132642
TI  - Structured, curriculum-based group teaching or unstructured, learner-centred
      group approaches?

PMID- 20132643
TI  - Teaching confrontation skills: a session on conflict resolution.

PMID- 20132644
TI  - How to ... Overcome barriers to effective work-based learning.

PMID- 20132645
TI  - Workplace-based assessment: a robust addition to general practice specialist
      training.

PMID- 20132646
TI  - Economic considerations: who needs them and why?

PMID- 20132648
TI  - Association between homocysteine and endothelial dysfunction markers in stroke
      disease.
AB  - BACKGROUND: Evidence shows that there is an increase in concentrations of markers
      of endothelial dysfunction immediately following acute ischaemic stroke. Several
      studies suggest that endothelial dysfunction may be partly caused by oxidation
      related to the effects of raised total plasma homocysteine. OBJECTIVE: The aim of
      this study was to measure changes in total plasma homocysteine and markers of
      endothelial dysfunction in stroke disease within a known period of time post
      infarct. SUBJECTS AND METHODS: We studied 40 acute ischaemic stroke patients
      (mean age +/- SD, 50.2 +/- 9.5 years) and 42 hospitalised non-stroke patients
      (mean age, 44.3 +/- 14.9 years). Fasting venous blood was obtained within 24 h, 3
      days and 7 days after the stroke onset and hospitalisation for non-stroke
      patients for measurements of total plasma homocysteine, markers of endothelial
      dysfunction including intracellular adhesion molecule (i-CAM), vascular cell
      adhesion molecule-1 (v-CAM) and leukocyte adhesion molecule-1 (E-selectin) and C
      reactive proteins (CRPs). RESULTS: We found no significant differences in
      baseline total plasma homocysteine, E-selectin, v-CAM, vitamin B(12), and folate
      concentrations between ischaemic stroke patients and non-stroke controls. i-CAM
      concentrations were significantly higher and CRPs non-significantly lower at
      baseline in stroke patients compared with controls. Although all endothelial
      dysfunction markers increased significantly during the study period, the rise in
      E-selectin levels was less than that seen in i-CAM, and v-CAM. Total plasma
      homocysteine concentrations showed positive correlations with creatinine (r =
      0.537; P < 0.02), and inverse correlations with both vitamin B(12) (r = -0.560; P
      < 0.001) and folate (r = -0.469; P < 0.002); however, there were no significant
      correlations between total plasma homocysteine or B-vitamins and markers of
      endothelial dysfunction in ischaemic stroke patients or controls. CONCLUSIONS: We
      found evidence of an increase in markers of endothelial dysfunction following
      acute ischaemic stroke but this had no relationship with total plasma
      homocysteine concentrations.

PMID- 20132649
TI  - Effects of chewing gum on cognitive function, mood and physiology in stressed and
      non-stressed volunteers.
AB  - RATIONALE: Recent research suggests that chewing gum may improve aspects of
      cognitive function and mood. There is also evidence suggesting that chewing gum
      reduces stress. It is important, therefore, to examine these two areas and to
      determine whether contextual factors (chewing habit, type of gum, and
      personality) modify such effects. OBJECTIVES: The aims of the present study were:
      (i) to determine whether chewing gum improved mood and mental performance; (ii)
      to determine whether chewing gum had benefits in stressed individuals; and (iii)
      to determine whether chewing habit, type of gum and level of anxiety modified the
      effects of gum. SUBJECTS AND METHODS: A cross-over study involving 133 volunteers
      was carried out. Each volunteer carried out a test session when they were chewing
      gum and without gum, with order of gum conditions counterbalanced across
      subjects. Baseline sessions were conducted prior to each test session.
      Approximately half of the volunteers were tested in 75 dBA noise (the stress
      condition) and the rest in quiet. Volunteers were stratified on chewing habit and
      anxiety level. Approximately, half of the volunteers were given mint gum and half
      fruit gum. The volunteers rated their mood at the start and end of each session
      and had their heart rate monitored over the session. Saliva samples were taken to
      allow cortisol levels (good indicator of alertness and stress) to be assayed.
      During the session, volunteers carried out tasks measuring a range of cognitive
      functions (aspects of memory, selective and sustained attention, psychomotor
      speed and accuracy). RESULTS: Chewing gum was associated with greater alertness
      and a more positive mood. Reaction times were quicker in the gum condition, and
      this effect became bigger as the task became more difficult. Chewing gum also
      improved selective and sustained attention. Heart rate and cortisol levels were
      higher when chewing which confirms the alerting effect of chewing gum.
      CONCLUSIONS: Overall, the results suggest that chewing gum produces a number of
      benefits that are generally observed and not context-dependent. In contrast to
      some previous research, chewing gum failed to improve memory. Further research is
      now required to increase our knowledge of the behavioral effects of chewing gum
      and to identify the underlying mechanisms.

PMID- 20132650
TI  - Central L-ornithine, but not polyamines, induces a hypnotic effect in neonatal
      chicks under acute stress.
AB  - To clarify whether L-ornithine and/or its metabolite involves sedative and
      hypnotic effects under social separation stress, the effects of
      intracerebroventricular (i.c.v.) injection of L-ornithine and polyamines
      (putrescine, spermidine and spermine) were compared in chicks. Birds were
      injected i.c.v. with 0.5 mumol of L-ornithine, putrescine, spermidine, spermine
      or saline (control). After injection, chicks were immediately separated from the
      flock and monitored for the number of distress vocalizations and various
      postures. L-Ornithine greatly attenuated the stress response and caused sedative
      and hypnotic effects. Among the polyamines, only putrescine attenuated distress
      vocalizations but did not induce sleep. In conclusion, the sedative and hypnotic
      effect of L-ornithine was mainly induced by L-ornithine itself, while the
      polyamines contributed to the sedative, but not hypnotic, effect under social
      separation stress.

PMID- 20132651
TI  - Glycogen stores are impaired in hypothalamic nuclei of rats malnourished during
      early life.
AB  - Perinatal nutrition has persistent influences on neural development and
      cognition. In humans and other animals, protein malnutrition during the perinatal
      period causes permanent changes, inducing to adulthood metabolic syndrome.
      Feeding is mainly modulated by neural and hormonal inputs to the hypothalamus.
      Hypothalamic glycogen stores are a source of glucose in high energetic demands,
      as during development of neural circuits. As some hypothalamic circuits are
      formed during lactation, we studied the effects of malnutrition, during the first
      10 days of lactation, on glycogen stores in hypothalamic nuclei involved in the
      control of energy metabolism. Female pregnant rats were fed ad libitum with a
      normal protein diet (22% protein). After delivery, each dam was kept with 6 male
      pups. During the first 10 days of lactation, dams from the experimental group
      received a protein-free diet and the control group a normoprotein diet. By post
      natal day 10 (P10), glycogen stores were very high in the arcuate nucleus and
      median eminence of control group. Glycogen stores decreased during development.
      In P20 control animals, glycogen stores were lower when compared to P10 control
      animals. Animals submitted to malnutrition presented a staining even lower than
      control ones. After P45, it was difficult to determine differences between
      control and diet groups because glycogen stores were reduced. We also showed that
      tanycytes were the cells presenting glycogen stores. Our data reinforce the
      concept that maternal nutritional state during lactation may be critical for
      neurodevelopment since it resulted in a low hypothalamic glycogen store, which
      may be critical for establishment of neuronal circuitry.

PMID- 20132652
TI  - Controlled-protein dietary regimens for Parkinson's disease.
AB  - Continuous levodopa replacement still is the most efficacious treatment for
      patients with Parkinson's disease. Unfortunately, the neutral aromatic amino
      acids contained in dietary proteins may compete with this drug for intestinal
      absorption and transport across the blood-brain barrier, thus limiting its
      efficacy and being responsible for the occurrence of motor fluctuations. Current
      guidelines recommend low-protein dietary regimens with protein redistribution, as
      shifting protein intake to the evening has proved to ameliorate the response to
      levodopa. However, adherence to this dietary regimen does not seem to be
      satisfactory and response is variable. Recent studies have shown that low-protein
      products designed for chronic renal failure patients are safe, tasty, well
      tolerated and useful in improving both adherence to low-protein dietary regimens
      and levodopa-related motor fluctuations. However, there still is the need to
      define the selection criteria for the patients who may benefit the most from
      adherence to this regimen.

PMID- 20132653
TI  - Undernutrition during either the pre- or immediate post-weaning period does not
      affect longevity in Quackenbush mice.
AB  - Diet restriction of rodents during a lengthy period of adult life, can lead to a
      marked increase in their life-span. However, undernutrition during gestation
      and/or the suckling period is, paradoxically, known to cause long-lasting
      'deleterious' deficits in body and brain structure. It remains uncertain whether
      or not such undernourished rodents also have an altered life-span. We have now
      investigated whether a short period of undernutrition of mice either before or
      immediately after the weaning period could modulate their life-span. Female out
      bred Quackenbush mice were undernourished for 40 days by standardised procedures
      either from conception until weaning or from weaning (day 19) till 60-days-of-age
      and compared to control mice that had been well-nourished throughout their lives.
      During the course of their life-span, some mice in each group became seriously
      ill and, because of ethical considerations, were required to be killed before
      their 'natural' death. The median age of mice at which they were required to be
      euthanized due to illness was significantly younger in the well-fed control group
      compared to the two previously undernourished groups. Of those mice that died of
      natural causes, it was found that about 90% died between about 300-700 (average,
      552-570; median, 556-595) days-of-age irrespective of group. Any differences
      between groups were not statistically significant. There were no significant
      differences between groups in the numbers of mice that survived beyond the 90th
      percentile of maximum life-span. Our results provided no evidence that a short
      period of undernutrition of Quackenbush mice either before or immediately after
      weaning has significant effects on their life-span. However, there was some
      evidence that, if it occurred, serious illness happened at a younger age in the
      well-nourished mice than those in the two diet-restricted groups.

PMID- 20132654
TI  - Immunohistochemical study of vasoactive intestinal peptide (VIP) enteric neurons
      in diabetic rats supplemented with L-glutamine.
AB  - The purpose of this work was to study the area of the varicosities of nerve
      fibers of myenteric neurons immunoreactive to vasoactive intestinal peptide (VIP
      IR) and of the cell bodies of VIP-IR submucosal neurons of the jejunum of
      diabetic rats supplemented with 2% L-glutamine. Twenty male rats were divided
      into the following groups: normoglycemic (N), normoglycemic supplemented with L
      glutamine (NG), diabetic (D) and diabetic supplemented with L-glutamine (DG).
      Whole-mounts of the muscle tunica and the submucosal layer were subjected to the
      immunohistochemical technique for neurotransmitter VIP identification.
      Morphometric analyses were carried out in 500 VIP-IR cell bodies of submucosal
      neurons and 2000 VIP-IR varicosities from each group. L-Glutamine supplementation
      to the normoglycemic animals caused an increase in the areas of the cell bodies
      (8.49%) and varicosities (21.3%) relative to the controls (P < 0.05). On the
      other hand, there was a decrease in the areas of the cell bodies (4.55%) and
      varicosities (28.9%) of group DG compared to those of group D (P < 0.05). It is
      concluded that L-glutamine supplementation was positive both to normoglycemic and
      diabetic animals.

PMID- 20132655
TI  - Whither the bone marrow transplant?
AB  - Bone marrow transplantation (BMT) has become an accepted and important medical
      intervention which has become a routine part of medical practice. Its utility
      has, however, been questioned recently in a number of diseases in which its role
      has been clearly established on the basis that there are better non-transplant
      therapeutic options. The suspicion that these moves to eradicate BMT as an option
      may not stem from purely scientific reasons has prompted the preparation of these
      personal reflections. I will focus this discussion only on two diseases in which
      BMT has been shown to be useful: chronic myelogenous leukemia (CML) and multiple
      myeloma (MM).

PMID- 20132656
TI  - Early cytomegalovirus infections following allogeneic stem cell transplantation:
      a comparison between non-malignant and malignant haematological disorders.
AB  - The haematological indications for allogeneic stem cell transplantation can be
      broadly divided into non-malignant and malignant disorders. We compared the
      incidence and risk factors for post-transplant cytomegalovirus (CMV) infections
      between these two biologically diverse subgroups of haematological conditions.
      Out of 105 allogeneic transplants, 64 and 41 were for underlying non-malignant
      and malignant indications respectively. CMV infections were significantly more
      frequent (P=0.016) in the malignant subgroup. Pre-transplant recipient CMV
      seropositivity in both subgroups (negative versus positive; non
      malignant,P=0.023; malignant, p<0.001), donor seropositivity (P=0.002) and acute
      graft-versus-host disease (GVHD) (P=0.02) in the non-malignant subgroup and > or
      =3 courses of previous cytotoxic therapy (P=0.023) in the malignant subgroup were
      found to be associated with an increased risk of CMV infections. On multivariate
      analysis, donor seropositivity in the non-malignant patients (negative versus
      positive,P=0.022; odds ratio: 0.18) and recipient seropositivity in patients with
      malignancies (negative versus positive; P=0.001, odds ratio: 0.01) were
      identified to be significant factors for risk of CMV infection.

PMID- 20132657
TI  - In vitro cell cycle dynamics of primitive hematopoietic cells from human
      umbilical cord blood.
AB  - The goal of the present study was to investigate the specific way in which
      recombinant stimulatory cytokines modulate the cell cycle dynamics of primitive
      hematopoietic cells in vitro. A human cord blood-derived cell population,
      enriched for CD34(+) Lin(-) cells, was obtained by negative selection and
      cultured in liquid cultures, in the absence or presence of recombinant
      stimulatory cytokines. The proportion of cells in each phase of the cell cycle,
      as well as the expression of cyclin D3, cyclin-dependent kinase-4 (cdk4), p16,
      p21 and p27, was determined at different time points. At the onset of culture,
      the vast majority of the cells were in the G(0)/G(1) phase of the cell cycle. In
      the absence of cytokines, most cells remained in such a phase and no cell cycle
      activity was detected throughout the culture period, which correlated with the
      absence of population doublings. In the presence of cytokines, approximately four
      cell cycles, with a proportionate population doubling, were observed within the
      first 4 days of culture. In cultures incorporating cytokines, expression levels
      of cyclin D3 and cdk4 were higher than in their absence; in contrast, the levels
      of the cell cycle inhibitors p16 and p21 were higher in cultures without
      cytokines. Levels of p27 were also higher in the presence of cytokines. Our
      results indicate that the proliferation of primitive hematopoietic cells in
      liquid culture is promoted by recombinant cytokines via the induction of specific
      positive regulators of the cell cycle and down-regulation of particular cell
      cycle inhibitors.

PMID- 20132658
TI  - Predictive value of (18)F-FDG hybrid PET/CT for the clinical outcome in patients
      with non-Hodgkin's lymphoma prior to and after autologous stem cell
      transplantation.
AB  - OBJECTIVE: Evaluation of therapeutic response in non-Hodgkin's lymphoma (NHL)
      patients with autologous stem cell transplantation (ASCT) is of great clinical
      significance. But the exact role of (18)F-fluorodeoxyglucose (FDG) imaging in NHL
      associated with ASCT is unclear. This study assessed the predictive value of
      (18)F-FDG hybrid PET/CT imaging for the clinical outcome such as progression-free
      survival (PFS) in patients with NHL prior to and after ASCT. METHODS: (18)F-FDG
      hybrid PET/CT was performed in 31 patients (24 male and 7 female) with
      pathologically confirmed NHL prior to and after ASCT. Mean age was 43.1+/-13.8
      years. No patients were lost to follow-up earlier than 1 year from ASCT.
      Sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and accuracy of (18)F-FDG hybrid PET/CT before ASCT were compared to
      the results after ASCT. The results of pre- and post-ASCT FDG hybrid PET/CT
      findings were correlated to PFS using Kaplan-Meier survival analysis. Regression
      analyses were employed to test for independence of established prognostic
      factors. RESULTS: Sixteen of 31 patients (52%) progressed/relapsed or died after
      a median follow-up of 7 months, the remaining 15 patients (48%) were disease free
      after a median follow-up of 24 months. Both pre- and post-ASCT, (18)F-FDG hybrid
      PET/CT findings showed high PPV, NPV and accuracy (85.7 versus 92.3%, 76.5 versus
      77.8% and 80.6 versus 83.9%). Both pre- and post-ASCT, (18)F-FDG hybrid PET/CT
      findings were strongly correlated with PFS (P<0.0005, significant). Of pre- ASCT
      FDG finding, the 1-year PFS rate for FDG-negative and FDG-positive patients was
      88.2 and 28.6%. Of post-ASCT FDG finding, the 1-year PFS rate for FDG-negative
      patients and FDG-positive patients was 88.9 and 23.1%. The regression model
      showed that the predictive value of FDG imaging owed its significance to the very
      high hazard ratio between patients with positive FDG imaging and negative FDG
      imaging (P<0.005) both pre- and post-ASCT. CONCLUSIONS: (18)F-FDG hybrid PET/CT
      imaging prior to and following autologous stem cell transplantation in NHL
      contains predictive information on the long-term clinical outcome.

PMID- 20132659
TI  - Factors associated with severe sepsis: prospective study of 94 neutropenic
      febrile episodes.
AB  - Severe sepsis defined as infection-induced organ dysfunction or hypoperfusion
      abnormalities predispose to septic shock and increased mortality in neutropenic
      setting. We aimed at determining predictors of severe sepsis in neutropenic
      patients. Between 1 October and 31 December 2007, 41 patients (21 with acute
      myeloid leukemia, 19 with acute lymphoid leukemia and one with autologous stem
      cell transplantation for a mantle cell lymphoma) with chemotherapy-induced
      neutropenia (<0.5 x 10(9)/l) lasting for more than 7 days were included in this
      study. The median age was 28 years (range: 3-58 years). All patients were on oral
      antibacterial (colistin and gentamicin) and anti-fungal (amphotericin B)
      prophylaxis. The first neutropenic febrile episode was treated with
      piperacillin/tazobactam and colistin IV; if the patient remains febrile at 48 h
      from the start of this first line of treatment, amphotericin B i.v. is added.
      Imipenem was introduced in the case of non-response and finally glycopeptides
      were introduced according to the IDSA criteria. Severe sepsis and septic shock
      are defined according to the criteria of the consensus conference of the
      ACCP/SCCM excluding the leukocyte count since all the patients were neutropenic.
      Ninety-four febrile episodes were observed: 27 microbiologically documented
      (28.7%), six clinically documented (6.3%) and 61 fever of unknown origin (65%).
      Microbiologically documented infections were: 13 Gram-negative organisms, 11 Gram
      positive organisms and three combined (Gram+ and -). Clinically documented
      infections were pneumonia (two), neutropenic enterocolitis (one), sinuses
      infection (one) and cutaneous infection (two). Severe sepsis accounted for 22
      febrile episodes. Factors associated with the occurrence of severe sepsis were:
      hypophosphatemia (<0.8 mmol/l; p=0.05, OR=3.9, 95% CI: 1.3-45.7), hypoproteinemia
      (<62 g/l; p=0.006, OR=4.1, 95% CI: 1.4-11.4) and non-adapted antibiotherapy at
      the onset of severe sepsis (p=0.019, OR=2.7, 95% CI: 1.02-7.39). However, heart
      rate/systolic blood pressure ratio <1.1 (p<0.001, OR=0.1, 95% CI: 0.03-0.31) and
      Creactive protein <80 mg (p=0.001, OR=0.14, 95% CI: 0.04-0.54) were not
      predictive.

PMID- 20132660
TI  - Nilotinib significantly induces apoptosis in imatinib-resistant K562 cells with
      wild-type BCR-ABL, as effectively as in parental sensitive counterparts.
AB  - Chronic myeloid leukemia (CML) is a hematological malignancy characterized by
      high levels of immature white blood cells. CML is caused by the translocation
      between chromosomes 9 and 22 (which results in the formation of the Philadelphia
      chromosome) creating BCR-ABL fusion protein. Imatinib and nilotinib are
      chemotherapeutic drugs which specifically bind to the BCR-ABL and inhibit cancer
      cells. Nilotinib is more effective in this respect than imatinib. We have shown
      that nilotinib induces apoptosis in imatinib-resistant K562 CML cells which have
      the wild-type BCR-ABL fusion gene almost to the same extent as it does in the
      parental sensitive cells by the increase in caspase-3 enzyme activity and the
      decrease in mitochondrial membrane potential. This effect of nilotinib, even in
      low concentrations, may indicate the efficacy of the usage of nilotinib in
      imatinib-resistant CML with less risk of undesired cytotoxic effects in the
      remaining cells of the body.

PMID- 20132661
TI  - Expression of WT1 gene in multiple myeloma patients at diagnosis: is WT1 gene
      expression a useful marker in multiple myeloma?
AB  - Monitoring patients with multiple myeloma during and after treatment for the
      presence of residual myeloma cells (minimal residual disease - MRD) has been
      shown to give a major insight into the effectiveness of treatment. It has been
      reported that Wilms' tumor gene (WT1) expression levels measured by real-time
      quantitative polymerase chain reaction was useful as an indicator of minimal
      residual disease in leukemia and myelodysplastic syndrome. The aim of this study
      was to measure levels of WT1 expression, in order to find a possible association
      between the expression of this gene and multiple myeloma at diagnosis. If an
      association was found, the WT1 gene could be evaluated as an MRD marker by
      comparison with other prognostic factors. We investigated peripheral blood WT1
      expression level measured by real-time light cycler quantitative polymerase chain
      reaction in 50 newly diagnosed multiple myeloma patients. The normal WT1 gene
      copy number was found to be <23/microl cDNA and all patients with myeloma were
      found to have normal WT1-mRNA levels. On this basis WT1 expression analyses is
      unlikely to be a useful genetic marker for routine clinical use in multiple
      myeloma patients at diagnosis.

PMID- 20132662
TI  - Aberrant expression of NK cell receptors in Epstein-Barr virus-positive
      gammadelta T-cell lymphoproliferative disorders.
AB  - To clarify the difference between gene expression signature of Epstein-Barr virus
      (EBV)-positive gammadelta T-cell lymphoproliferative disorders (LPD) and those in
      normal gammadelta T-cells, we set out to determine gene expression profiling
      using three gammadelta T-cell lines derived from patients with EBV-positive
      gammadelta T-cell LPD. Gene expression profiling using an Affymetrix Genechip
      revealed a unique gene expression pattern of NK cell receptors in gammadelta T
      LPD cell lines. Genes encoding killer cell lectin-like receptors (KLR), such as
      KLRG1 and KLRB1 (CD161), were generally low in gammadelta T-LPD cell lines, while
      killer cell immunoglobulin-like receptors varied among cell lines. In addition,
      expression of CD161 surface antigen was found to be remarkably decreased in
      gammadelta T-LPD cell lines by flow cytometric analysis. We conclude that
      gammadelta T-cell expansion in EBV-positive gammadelta T-LPD is in part due to
      inappropriate expression of the NK cell receptors which related to impaired
      function cytotoxic T cells.

PMID- 20132663
TI  - Characterization of conserved CDR3 sequence of TCR alpha- and beta-chain genes in
      peripheral blood T-cells from patients with diffuse large B-cell lymphoma.
AB  - T-cell immunodeficiency is a common feature in cancer patients, but clonally
      expanded T cells which were considered to have the specific anti-tumor
      cytotoxicity can be identified in most cancer patients, including those with
      hematological malignancies. We previously reported that there were skewed usages
      of T-cell receptor (TCR) Valpha and TCR Vbeta subfamily in clonally expanded T
      cells in the peripheral blood (PB) of patients with diffuse large B-cell lymphoma
      (DLBCL). In order to investigate the characteristics of the complementarity
      determining region 3 (CDR3) of TCR alpha- and beta-chain genes in clonally
      expanded T cells, the sequences of TCR-CDR3 region of clonally expanded TCR
      Valpha and TCR Vbeta subfamily T cells were analyzed. Conserved amino acid motifs
      of TCR-CDR3 region were identified in different clonally expanded T cells.
      RSxYNTDKLI, SxGG, GGS, and DSxY motifs were found in the TCR Valpha subfamily T
      cell clones, while SxGTG, SRG, and GTxD motifs existed in the TCR Vbeta subfamily
      T-cell clones. Moreover, the TCR harboring conserved motif in CDR3 region of some
      T-cell clones had high homology in the three-dimensional spatial structures.
      These findings revealed the mono/oligoclonally expanded T cells were derived from
      the stimulation of some antigens in the PB of patients with DLBCL, and may be
      recognizing an identical antigenic epitope.

PMID- 20132664
TI  - Clinical, genetic and cytogenetic study of Fanconi anemia in an Indian
      population.
AB  - Fanconi anemia (FA) is a rare autosomal recessive genetic disease, associated
      with congenital anomalies and a predisposition to cancers. FA patients exhibit
      spontaneous chromosome breakage and FA cells are sensitive to DNA interstrand
      crosslink agents and expresses high frequency of chromosome breakage. Recently 13
      genes have been shown to be involved with the FA phenotype. We have carried out a
      detailed study in clinically diagnosed FA patients in an Indian population.
      Thirty three patients were clinically diagnosed with FA and had aplastic anemia
      and bleeding abnormalities. The genetic analysis revealed a significantly
      (P<0.0001) high frequency (36.4%) of parental consanguinity in FA patients
      compared to controls (3.33%). Chromosomal analysis revealed spontaneous
      chromosome breakage in 63.64% FA patients. The mitomycin C and diepoxybutane
      induced cultures showed a significantly (P<0.001) high frequency of chromosome
      breakage and radial formation compared to controls. Among 33 patients, nine
      (27.27%) patients developed malignancies and chromosomal abnormalities were
      detected in five (55.5%) patients bone marrow cells including monosomy 5 and 7,
      trisomy 10, der(1q) and inv(7). Cytogenetic investigation is important in
      aplastic anemia to rule out FA. The clinical presentation and the associated high
      frequency of consanguinity in FA, and the molecular analysis are complementary in
      the study of an Indian population.

PMID- 20132665
TI  - Behavior of Escherichia coli O157:H7 on damaged leaves of spinach, lettuce,
      cilantro, and parsley stored at abusive temperatures.
AB  - Recent foodborne illness outbreaks associated with the consumption of leafy green
      produce indicates a need for additional information on the behavior of pathogenic
      bacteria on these products. Previous research indicates that pathogen growth and
      survival is enhanced by leaf damage. The objective of this study was to compare
      the behavior of Escherichia coli O157:H7 on damaged leaves of baby Romaine
      lettuce, spinach, cilantro, and parsley stored at three abusive temperatures (8,
      12, and 15 degrees C). The damaged portions of leaves were inoculated with
      approximately 10(5) CFU E. coli O157:H7 per leaf. The pathogen grew on damaged
      spinach leaves held for 3 days at 8 and 12 degrees C (P < 0.05), with the
      population increasing by 1.18 and 2.08 log CFU per leaf, respectively. E. coli
      O157:H7 did not grow on damaged Romaine leaves at 8 or 12 degrees C, but growth
      was observed after 8 h of storage at 15 degrees C, with an increase of less than
      1.0 log. Growth of E. coli O157:H7 on Romaine lettuce held at 8 or 12 degrees C
      was enhanced when inocula were suspended in 0.05% ascorbic acid, indicating the
      possibility of inhibition by oxidation reactions associated with tissue damage.
      Damaged cilantro and Italian parsley leaves held at 8 degrees C for 4 days did
      not support the growth of E. coli O157:H7. Behavior of the pathogen in leaf
      extracts differed from behavior on the damaged tissue. This study provides
      evidence that the damaged portion of a leafy green is a distinct growth niche
      that elicits different microbial responses in the various types of leafy greens.

PMID- 20132666
TI  - A quantitative PCR assay for rapid detection of Shigella species in fresh
      produce.
AB  - A quantitative PCR (qPCR) assay with two primers and a TaqMan probe targeting
      conserved regions of the specific ipaH gene of Shigella species and
      enteroinvasive Escherichia coli (EIEC) were developed. This qPCR assay was used
      to identify 206 Shigella strains (including four Shigella species with all
      serotypes and two provisional Shigella species), 3 EIEC strains, and 113 non
      Shigella strains with 100% accuracy. Pure cultures of six Shigella reference
      strains were used to derive standard curves to determine the detection limit and
      efficiency of the qPCR method. The ipaH qPCR assay had an equally low detection
      limit (0.12 to 0.74 CFU per PCR) for the four Shigella species tested. The
      average qPCR efficiency was 99.29% (95.36 to 103.92%). The detection limit of the
      qPCR assay tested on 15 varieties of inoculated fresh produce ranged from 0.4 to
      16 CFU/100 ml of buffer rinse. This qPCR assay took the variation of wild-type
      nucleotides into consideration and was used successfully to screen fresh produce.
      This highly sensitive qPCR assay can be completed within 24 h and has potential
      use as a screening tool for all four Shigella species and EIEC in food samples.

PMID- 20132667
TI  - Carvacrol and cinnamaldehyde inactivate antibiotic-resistant Salmonella enterica
      in buffer and on celery and oysters.
AB  - The emergence of antibiotic-resistant Salmonella is of concern to food
      processors. The objective of this research was to identify antimicrobial
      activities of cinnamaldehyde and carvacrol against antibiotic-resistant
      Salmonella enterica in phosphate-buffered saline (PBS) and on celery and oysters.
      Twenty-three isolates were screened for resistance to seven antibiotics. Two
      resistant and two susceptible strains were chosen for the study. S. enterica
      cultures (10(5) CFU/ml) were added to different concentrations of cinnamaldehyde
      and carvacrol (0.1, 0.2, 0.3, and 0.4% [vol/vol]) in PBS, mixed, and incubated at
      37 degrees C. Samples were taken at 0, 1, 5, and 24 h for enumeration. Celery and
      oysters were inoculated with S. enterica (10(6-7) CFU/ml), treated with 1%
      cinnamaldehyde or 1% carvacrol, incubated at 4 degrees C, and then sampled for
      enumeration on days 0 and 3. Both antimicrobials induced complete inactivation of
      S. enterica in PBS at 0.3 and 0.4% on exposure, and on 0.2% in 1 h. Exposure to
      cinnamaldehyde at 0.1% inactivated all pathogens at 1 h, and survivors were
      observed only for Salmonella Newport with 0.1% carvacrol at 1 h. In celery, 1%
      carvacrol reduced S. enterica populations to below detection on day 0, while 1%
      cinnamaldehyde reduced populations by 1 and 2.3 log on day 0 and day 3,
      respectively. In oysters, both antimicrobials caused about 5-log reductions on
      day 3. These results show the potential antimicrobial effects of carvacrol and
      cinnamaldehyde against antibiotic-resistant S. enterica in vitro and in foods.

PMID- 20132668
TI  - Rapid detection and differentiation of Campylobacter jejuni, Campylobacter coli,
      and Campylobacter lari in food, using multiplex real-time PCR.
AB  - A multiplex real-time PCR assay based on four differently labeled TaqMan probes
      for detection and differentiation of the thermophilic Campylobacter species C.
      jejuni, C. coli, and C. lari was established and validated in food products. This
      assay combines two previously published PCR assays for C. jejuni and C. coli with
      a newly developed detection assay for C. lari and an internal amplification
      control system. The selectivity of the method was determined by analyzing 70
      Campylobacter strains and 43 strains of other bacteria. The sensitivity was 50 fg
      of C. jejuni and C. lari DNA and 500 fg of C. coli DNA per PCR. It was possible
      to detect 1 to 10 CFU/25 g of food before preenrichment of all three species.
      More than 400 samples of various foods (poultry, seafood, and meat) were analyzed
      after 48 h of preenrichment parallel to the conventional diagnostic method of
      culture and biochemical identification. Using the established real-time PCR
      assay, 55.4% of the samples were recognized as positive for thermophilic
      Campylobacter species, whereas with the conventional method only 40.3% of the
      samples were positive. The real-time PCR assay also detected contaminations with
      two different Campylobacter species in 32.6% of the analyzed poultry samples, a
      finding of epidemiological interest. Compared with the original PCR method, which
      was established for the differentiation of bacterial isolates of C. jejuni and C.
      coli, this new method also detects and distinguishes C. lari, was validated as an
      analytical tool for food analysis, and provides reliable and extensive results
      within 2 days.

PMID- 20132669
TI  - Caprylic Acid reduces enteric campylobacter colonization in market-aged broiler
      chickens but does not appear to alter cecal microbial populations.
AB  - Campylobacter is a leading cause of foodborne illness in the United States, and
      epidemiological evidence indicates poultry products to be a significant source of
      human Campylobacter infections. Caprylic acid, an eight-carbon medium-chain fatty
      acid, reduces Campylobacter colonization in chickens. How caprylic acid reduces
      Campylobacter carriage may be related to changes in intestinal microflora. To
      evaluate this possibility, cecal microbial populations were evaluated with
      denaturing gradient gel electrophoresis from market-age broiler chickens fed
      caprylic acid. In the first trial, chicks (n = 40 per trial) were assigned to
      four treatment groups (n = 10 birds per treatment group): positive controls
      (Campylobacter, no caprylic acid), with or without a 12-h feed withdrawal before
      slaughter; and 0.7% caprylic acid supplemented in feed for the last 3 days of the
      trial, with or without a 12-h feed withdrawal before slaughter. Treatments were
      similar for trial 2, except caprylic acid was supplemented for the last 7 days of
      the trial. At age 14 days, chicks were orally challenged with Campylobacter
      jejuni, and on day 42, ceca were collected for denaturing gradient gel
      electrophoresis and Campylobacter analysis. Caprylic acid supplemented for 3 or 7
      days at 0.7% reduced Campylobacter compared with the positive controls, except
      for the 7-day treatment with a 12-h feed withdrawal period. Denaturing gradient
      gel electrophoresis profiles of the cecal content showed very limited differences
      in microbial populations. The results of this study indicate that caprylic acid's
      ability to reduce Campylobacter does not appear to be due to changes in cecal
      microflora.

PMID- 20132670
TI  - Effect of organic acids and marination ingredients on the survival of
      Campylobacter jejuni on meat.
AB  - The aim of this study was to determine whether marination of chicken meat in
      different food ingredients can be used to reduce populations of Campylobacter
      jejuni. C. jejuni strains were exposed to different organic acids (tartaric,
      acetic, lactic, malic, and citric acids) and food marinating ingredients at 4
      degrees C in broth and on chicken meat. The organic acids (0.5%) reduced
      populations of C. jejuni in broth (chicken juice and brain heart infusion broth)
      by 4 to 6 log units (after 24 h); tartaric acid was the most efficient treatment.
      Large strain variation was observed among 14 C. jejuni isolates inoculated in
      brain heart infusion broth containing 0.3% tartaric acid. On chicken meat
      medallions, reductions of C. jejuni were 0.5 to 2 log units when tartaric acid
      solutions (2, 4, 6, and 10%) were spread onto the meat. Analysis of acidic food
      ingredient (e.g., vinegar, lemon juice, pomegranate syrup, and soya sauce)
      revealed that such ingredients reduced counts of C. jejuni by at least 0.8 log
      units on meat medallions. Three low pH marinades (pH < 3) based on pomegranate
      syrup, lemon juice, and white wine vinegar were prepared. When applied to whole
      filets, these marinades resulted in a reduction of approximately 1.2 log units
      after 3 days of storage. Taste evaluations of chicken meat that had been
      marinated and then fried were graded positively for flavor and texture. Thus,
      success was achieved in creating a marinade with an acceptable taste that reduced
      the counts of C. jejuni.

PMID- 20132671
TI  - Antilisterial effects of gravinol-s grape seed extract at low levels in aqueous
      media and its potential application as a produce wash.
AB  - Grape seed extract (GSE) is a rich source of proanthocyanidins, a class of
      natural antioxidants reported to have wide-ranging bioactivity as anti
      inflammatory, anticarcinogenic, and antimicrobial agents. The ability of GSE to
      rapidly inactivate Listeria monocytogenes in vitro and the generally recognized
      as safe status of GSE make this extract an attractive candidate for control of
      Listeria in or on foods. Previously, GSE has been used at relatively high
      concentrations (1%) in complex food matrices and in combination with other
      antimicrobials. We sought to characterize the antilisterial effects of a
      commercial GSE preparation (Gravinol-S) alone at much lower concentrations
      (0.00015 to 0.125%) in aqueous solution and to test its possible use as an
      antimicrobial wash for fresh produce surfaces. Based on broth microdilution
      tests, the MICs of GSE against L. monocytogenes Scott A and Listeria innocua ATCC
      33090 were as low as 50 and 78 mug ml(-1), respectively. GSE was evaluated in
      0.85% saline against live cells of L. innocua via flow cytometry, using propidium
      iodide as a probe for membrane integrity. At sub-MICs and after only 2 min of
      exposure, treatment with GSE caused rapid permeabilization and clumping of L.
      innocua, results that we confirmed for L. monocytogenes using fluorescence
      microscopy and Live/Dead staining. At higher concentrations (0.125%), GSE reduced
      viable cell counts for L. monocytogenes by approximately 2 log units within 2 min
      on tomato surfaces. These results suggest the potential for GSE as a natural
      control of Listeria spp. on low-complexity foods such as tomatoes.

PMID- 20132672
TI  - Quantitative microbial risk assessment for Escherichia coli O157:H7, salmonella,
      and Listeria monocytogenes in leafy green vegetables consumed at salad bars.
AB  - Fresh vegetables are increasingly recognized as a source of foodborne outbreaks
      in many parts of the world. The purpose of this study was to conduct a
      quantitative microbial risk assessment for Escherichia coli O157:H7, Salmonella,
      and Listeria monocytogenes infection from consumption of leafy green vegetables
      in salad from salad bars in The Netherlands. Pathogen growth was modeled in
      Aladin (Agro Logistics Analysis and Design Instrument) using time-temperature
      profiles in the chilled supply chain and one particular restaurant with a salad
      bar. A second-order Monte Carlo risk assessment model was constructed (using
      @Risk) to estimate the public health effects. The temperature in the studied cold
      chain was well controlled below 5 degrees C. Growth of E. coli O157:H7 and
      Salmonella was minimal (17 and 15%, respectively). Growth of L. monocytogenes was
      considerably greater (194%). Based on first-order Monte Carlo simulations, the
      average number of cases per year in The Netherlands associated the consumption
      leafy greens in salads from salad bars was 166, 187, and 0.3 for E. coli O157:H7,
      Salmonella, and L. monocytogenes, respectively. The ranges of the average number
      of annual cases as estimated by second-order Monte Carlo simulation (with
      prevalence and number of visitors as uncertain variables) were 42 to 551 for E.
      coli O157:H7, 81 to 281 for Salmonella, and 0.1 to 0.9 for L. monocytogenes. This
      study included an integration of modeling pathogen growth in the supply chain of
      fresh leafy vegetables destined for restaurant salad bars using software designed
      to model and design logistics and modeling the public health effects using
      probabilistic risk assessment software.

PMID- 20132673
TI  - Colonization of a newly constructed commercial chicken further processing plant
      with Listeria monocytogenes.
AB  - This study was undertaken to determine potential sources of Listeria
      monocytogenes in a newly constructed chicken further processing plant and
      document the eventual colonization of the facility by this pathogen. To ascertain
      the colonization status of the plant, floor drains were sampled after a
      production shift and again after a cleanup shift on roughly a monthly basis for
      21 months. Potential sources of L. monocytogenes to the plant included incoming
      raw meat, incoming fresh air, and personnel. Nearby environment and community
      samples were also examined. All L. monocytogenes detected were subjected to DNA
      sequence-based subtyping. L. monocytogenes was not detected in the plant before
      the commencement of processing operations. Within 4 months, several subtypes of
      L. monocytogenes were detected in floor drains, both before and after cleaning
      and sanitizing operations. No L. monocytogenes was detected on filters for
      incoming air, samples associated with plant employees, or a nearby discount
      shopping center. One subtype of L. monocytogenes was detected in a natural stream
      near the plant; however, this subtype was never detected inside the plant. Eight
      subtypes of L. monocytogenes were detected in raw meat staged for further
      processing; one of the raw meat subtypes was indistinguishable from a persistent
      drain subtype recovered after cleaning on eight occasions in four different
      drains. Poultry further processing plants are likely to become colonized with L.
      monocytogenes; raw product is an important source of the organism to the plant.

PMID- 20132674
TI  - Applicability of bacteriocinogenic Lactobacillus pentosus 31-1 as a novel
      functional starter culture or coculture for fermented sausage manufacture.
AB  - The technological feasibility of producing fermented sausages using the
      bacteriocin-producing Lactobacillus pentosus 31-1, isolated from a traditional
      Chinese fermented meat product (Xuanwei ham), was evaluated. Strain 31-1 was used
      both as a single starter and in coculture for manufacture of fermented sausages.
      The microbiological and physicochemical properties (color, texture, and sensory
      quality) and the production of bacteriocin during ripening of these products were
      compared with those characteristics of sausages produced with a commercial meat
      starter. Challenge tests were performed using Listeria innocua or Staphylococcus
      aureus as target strains. The addition of L. pentosus 31-1 can significantly
      reduce L. innocua and S. aureus populations during all ripening phases. Free
      amino acid and free fatty acid analysis suggested that strain 31-1 might have
      proteolytic and lipolytic activity. The use of this strain resulted in a final
      product with a brighter surface and better texture and sensory profiles. A
      maximum bacteriocin (pentocin 31-1) concentration of 640 AU/g was detected in
      homogenized sausages with added L. pentosus 31-1. The bacteriocin-producing
      strain L. pentosus 31-1 could be used as a novel functional starter culture or
      coculture for sausage fermentation.

PMID- 20132675
TI  - Inactivation kinetics of Alicyclobacillus acidoterrestris spores in orange juice
      by ohmic heating: effects of voltage gradient and temperature on inactivation.
AB  - The effectiveness of ohmic and conventional heating for reducing spores of
      Alicyclobacillus acidoterrestris was investigated in commercial pasteurized
      orange juice. The kinetic parameters (D- and z-values) were determined during
      ohmic and conventional heating. The effects of temperature (70, 80, and 90
      degrees C) and heating time (0, 10, 15, 20, and 30 min) on inactivation of A.
      acidoterrestris spores during ohmic heating in orange juice were significant (P <
      0.05). For 70 degrees C, the voltage gradient also had an effect on inactivation
      kinetics. At 30 V/cm, D-values at 70, 80, and 90 degrees C were 58.48, 12.24, and
      5.97 min, respectively. D-values at corresponding temperatures for conventionally
      heated spores were 83.33, 15.11, and 7.84 min, respectively. Results showed
      significantly higher lethality for spores treated with ohmic heating than for
      spores treated with conventional heating. Conventional heating was ineffective
      for pasteurizing orange juice, whereas the maximum ohmic heating treatment
      applied at 30 V/cm was sufficient to inactivate 5 log units of A. acidoterrestris
      spores.

PMID- 20132676
TI  - Comparison between quantitative real-time reverse transcription PCR results for
      norovirus in oysters and self-reported gastroenteric illness in restaurant
      customers.
AB  - Norovirus is the principal agent of bivalve shellfish-associated gastroenteric
      illness worldwide. Numerous studies using PCR have demonstrated norovirus
      contamination in a significant proportion of both oyster and other bivalve
      shellfish production areas and ready-to-eat products. By comparison, the number
      of epidemiologically confirmed shellfish-associated outbreaks is relatively low.
      This study attempts to compare norovirus RNA detection in Pacific oysters
      (Crassostrea gigas) by quantitative real-time reverse transcription PCR (RT-PCR)
      and human health risk. Self-reported customer complaints of illness in a
      restaurant setting (screened for credible norovirus symptoms) were compared with
      presence and levels of norovirus as determined by real-time RT-PCR for the batch
      of oysters consumed. No illness was reported for batches consistently negative
      for norovirus by real-time RT-PCR. However, norovirus was detected in some
      batches for which no illness was reported. Overall presence or absence of
      norovirus showed a significant association with illness complaints. In addition,
      the batch with the highest norovirus RNA levels also resulted in the highest rate
      of reported illness, suggesting a linkage between virus RNA levels and health
      risks. This study suggests that detection of high levels of norovirus RNA in
      oysters is indicative of a significantly elevated health risk. However, illness
      may not necessarily be reported after detection of norovirus RNA at low levels.

PMID- 20132677
TI  - Estimating parametric distributions of storage time and temperature of ready-to
      eat foods for U.S. households.
AB  - Home refrigeration temperatures and product storage times are important factors
      for controlling the growth of Listeria monocytogenes in refrigerated ready-to-eat
      foods. In 2005, RTI International, in collaboration with Tennessee State
      University and Kansas State University, conducted a national survey of U.S.
      adults to characterize consumers' home storage and refrigeration practices for 10
      different categories of refrigerated ready-to-eat foods. No distributions of
      storage time or refrigeration temperature were presented in any of the resulting
      publications. This study used classical parametric survival modeling to derive
      parametric distributions from the RTI International storage practices data set.
      Depending on the food category, variability in product storage times was best
      modeled using either exponential or Weibull distributions. The shape and scale of
      the distributions varied greatly depending on the food category. Moreover, the
      results indicated that consumers tend to keep a product that is packaged by a
      manufacturer for a longer period of time than a product that is packaged at
      retail. Refrigeration temperatures were comparable to those previously reported,
      with the variability in temperatures best fit using a Laplace distribution, as an
      alternative to the empirical distribution. In contrast to previous research,
      limited support was found for a correlation between storage time and temperature.
      The distributions provided in this study can be used to better model consumer
      behavior in future risk assessments.

PMID- 20132678
TI  - Aminopeptidase activity by spoilage bacteria and its relationship to microbial
      load and sensory attributes of poultry legs during aerobic cold storage.
AB  - The shelf life of poultry legs stored aerobically and the possible role of the
      aminopeptidase activity of gram-negative bacteria (p-nitroaniline test) as a
      predictor of poultry spoilage were evaluated on the basis of microbiological and
      sensory parameters. Chicken legs (n = 30) obtained immediately after evisceration
      in a local poultry processing plant were kept under aerobic refrigeration (4 +/-
      1 degrees C) for 7 days. Microbiological (counts of aerobic bacteria and
      psychrotrophs) and sensory (odor, color, and general acceptability on a hedonic
      scale of 1 to 9) parameters and aminopeptidase activity (absorbance at 390 nm
      [A(390)]) determinations were performed after 0, 1, 3, 5, and 7 days of storage.
      Aerobic plate counts of 7 log CFU/g and a score of 6 for general acceptability
      were used as indicators of the end point of shelf life. Strong correlations (r >
      or = 0.76; P < 0.001) were obtained between bacterial counts, hedonic scores, and
      A(390) values. Samples were judged as unacceptable (shelf-life end point) after 2
      and 4 days on the basis of sensory and microbiological analyses, respectively.
      A(390) values of 0.52 and 0.89 (corresponding to p-nitroaniline concentrations of
      6.25 and 10.7 microg/ml, respectively) are proposed as the upper limits for
      acceptability on the basis of sensory and microbiological determinations,
      respectively. However, these recommendations are based on a small set of samples,
      and their general application is yet to be verified.

PMID- 20132679
TI  - Qualitative studies of the food safety knowledge and perceptions of transplant
      patients.
AB  - Organ and stem cell transplant patients are at risk for foodborne illness due to
      disease and medically induced immunosuppression. The food safety knowledge and
      informational needs of these groups have not been documented in the literature.
      The objectives of this study were to assess transplant patients' food safety
      knowledge and perceptions, to probe the likelihood of practicing safe food
      handling behavior, and to test an educational strategy for future food safety
      interventions aimed at transplant patients. Subjects were organ or stem cell
      transplant patients, or their family care providers. Research was conducted in
      inpatient or outpatient facilities at a large, Midwestern United States
      comprehensive cancer and transplant center. Differences in survey data between
      the organ and stem cell transplant groups were determined by Student's t tests.
      Ethnographic methods were used to analyze qualitative focus groups and interview
      data for themes. Organ transplant patients had less motivation to follow food
      safety recommendations than did stem cell transplant patients, and they were more
      likely to consume risky foods. Stem cell transplant patients overall had a better
      understanding of their susceptibility to foodborne illness and had better
      prepared themselves with the knowledge and behavior changes needed to protect
      their health. Educational materials aimed at communicating food safety
      information for transplant patients were evaluated by patients and judged
      acceptable. This study found that organ transplant and stem cell transplant
      patients are distinct patient populations, with differing perceptions regarding
      the seriousness of foodborne illness and willingness to adopt preventative food
      handling practices. Population differences should be accounted for in food safety
      educational strategies.

PMID- 20132680
TI  - Impact of water activity and temperature on growth and alternariol and
      alternariol monomethyl ether production of Alternaria alternata isolated from
      soybean.
AB  - The objective of this study was to determine the effect of water activity (a(w);
      0.995, 0.98, 0.96, 0.94, 0.92, and 0.90), temperature (5, 18, 25, and 30 degrees
      C), incubation time (7 to 35 days), and their interactions on mycelial growth and
      alternariol (AOH) and alternariol monomethyl ether (AME) production. Two
      Alternaria alternata strains isolated from soybeans in Argentina were grown on 2%
      soybean extract agar. Maximum growth rates were obtained at the highest a(w)
      (0.995) and 25 degrees C, with growth decreasing as the water availability of the
      medium was reduced. Maximum amount of AOH was produced at 0.98 a(w) and 25
      degrees C for both strains. Maximum AME production was obtained for both strains
      at 30 degrees C but different a(w) values, 0.92 and 0.94, for the strains RC 21
      and RC 39, respectively. The concentrations of both toxins varied considerably
      depending on the a(w) and temperature interactions assayed. The two metabolites
      were produced from 5 to 30 degrees C and at a(w) values of 0.92 to 0.995.
      Although at 5 and 18 degrees C little mycotoxin was produced at a(w) lower than
      0.94. Two-dimensional profiles of a(w) by temperature interactions were developed
      from these data to identify areas where conditions indicate a significant risk
      from AOH and AME accumulation on soybeans. All the conditions of a(w) and
      temperature that resulted in maximum production of both toxins are those found
      during soybean development in the field. Thus, field conditions are likely to be
      conducive to optimum A. alternata growth and toxin production.

PMID- 20132681
TI  - Four-year surveillance for ochratoxin a and fumonisins in retail foods in Japan.
AB  - Between 2004 and 2007 we examined foods from Japanese retail shops for
      contamination with ochratoxin A (OTA) and fumonisins B(1), B(2), and B(3). A
      total of 1,358 samples of 27 different products were examined for OTA, and 831
      samples of 16 different products were examined for fumonisins. The limits of
      quantification ranged from 0.01 to 0.5 microg/kg for OTA and 2 to 10 microg/kg
      for the fumonisins. OTA was detected in amounts higher than limits of
      quantification in wheat flour, pasta, oatmeal, rye, buckwheat flour and dried
      buckwheat noodles, raisins, wine, beer, coffee beans and coffee products,
      chocolate, cocoa, and coriander. OTA was found in more than 90% of the samples of
      instant coffee and cocoa, and the highest concentration of OTA, 12.5 microg/kg,
      was detected in raisins. The concentration of OTA in oatmeal, rye, raisins, wine,
      and roasted coffee beans varied remarkably from year to year. Fumonisins were
      detected in frozen and canned corn, popcorn grain, corn grits, cornflakes, corn
      soups, corn snacks, beer, soybeans, millet, and asparagus. The highest
      concentrations of fumonisins B(1), B(2), and B(3) were detected in corn grits
      (1,670, 597, and 281 microg/kg, respectively). All of the samples of corn grits
      were contaminated with fumonisins, and more than 80% of the samples of popcorn
      grain and corn snacks contained fumonisins. OTA and fumonisins were detected in
      several food products in Japan; however, although Japan has not set regulatory
      levels for these mycotoxins, their concentrations were relatively low.

PMID- 20132682
TI  - Use of electron beam radiation for the reduction of Salmonella enterica serovars
      typhimurium and Tennessee in peanut butter.
AB  - Peanut butter and peanut paste products were implicated as the vehicle of
      contamination in an outbreak of Salmonella Typhimurium, which began in September
      2008, and in the November 2006 outbreak of Salmonella Tennessee. Therefore, this
      study evaluated the effectiveness of electron beam (e-beam) radiation for the
      reduction of Salmonella serovars Tennessee (ATCC 10722) and Typhimurium (ATCC
      14028) in creamy peanut butter. Each strain was studied independently. Peanut
      butter samples were inoculated with approximately 8.0 log CFU/g of Salmonella,
      and exposed to e-beam doses ranging from 0 to 3.1 kGy. Doses were confirmed with
      film dosimetry. Survivors were enumerated by standard spread plating on
      nonselective tryptic soy agar (TSA) and selective xylose-lysine-desoxycholate
      agar (XLD) media. Salmonella Tennessee was more susceptible to e-beam radiation,
      with 5.00- and 6.75-log reduction of cells on TSA and XLD, respectively, at the
      approximate e-beam dose of 3.0 kGy. Salmonella Typhimurium was reduced by 4.19
      and 4.85 log on TSA and XLD, respectively, at the approximate e-beam dose of 3.0
      kGy. D(10)-values show that Salmonella Typhimurium was more resistant (0.82 +/-
      0.02 and 0.73 +/- 0.01 kGy on TSA and XLD, respectively) than was Salmonella
      Tennessee (0.72 +/- 0.02 and 0.60 +/- 0.01 kGy on TSA and XLD, respectively) to e
      beam radiation (P < 0.05). The recovery on growth and selective media were
      different (P < 0.05), indicating cell injury. The results of this study
      demonstrate that e-beam radiation may be an effective processing step for the
      nonthermal inactivation of Salmonella in peanut butter.

PMID- 20132683
TI  - Reduction of Escherichia coli O157:H7 in Fresh Spinach, using lactic acid
      bacteria and chlorine as a multihurdle intervention.
AB  - A 12-day shelf life study was conducted at 7 degrees C to determine whether
      Escherichia coli O157:H7 on spinach can be controlled effectively by selected
      strains of lactic acid bacteria (LAB) alone or in combination with chlorine as a
      multihurdle intervention. The multihurdle intervention consisted of both LAB and
      chlorine and was applied to spinach as a rinse and evaluated in comparison to LAB
      alone and chlorine and water rinses. Reductions achieved by all treatments also
      were compared with those observed for an inoculated control. The spinach was
      inoculated by submersion in a solution containing an E. coli O157:H7 cocktail at
      1.0 x 10(6) CFU/ml. LAB were applied postharvest at a concentration of 2.0 x
      10(8) CFU/ml, and 200 ppm of chlorine was used for the chlorine rinse. All
      spinach samples were packaged in commercial packaging, held in a retail display
      case, and tested for E. coli O157:H7 on days 0, 1, 3, 6, 9, and 12 using the Neo
      Grid filtration system and CHROMagar. Survival of LAB throughout the shelf life
      also was determined. Significant reductions in pathogen populations were achieved
      by water (P = 0.0008), LAB (P < 0.0001), chlorine (P < 0.0001), and multihurdle
      (P < 0.0001) treatments when compared with controls. The multihurdle treatment
      produced the greatest reduction from control populations, a reduction of 1.91 log
      CFU/ml. This reduction was significantly greater than that achieved with water (P
      < 0.0001), LAB (P = 0.0025), and chlorine (P < 0.0001) alone, indicating that the
      application of chlorine and LAB is most effective as a combination treatment. The
      results obtained from this study indicate that the industry standard chlorine
      wash may be more effective when applied in combination with LAB.

PMID- 20132684
TI  - Validation of a washing and sanitizing procedure for cantaloupes at a mexican
      packing facility.
AB  - In-plant validation of an alternative washing and sanitizing method was conducted
      at a cantaloupe packing operation in Mexico. This method consisted of a spray
      water wash followed by spraying warm (55 to 60 degrees C) 2% (L)-lactic acid
      solution and was compared with the existing method of spray washing the melons
      with tap water followed by immersion in a chlorinated water tank. Surface samples
      (100 cm(2)) were collected from 160 melons subjected to each processing method
      and tested for counts of aerobic bacteria, coliforms, and Escherichia coli. The
      aerobic plate counts from cantaloupes washed in the dump tank ranged from 3.6 to
      5.2 log CFU/cm(2) and were significantly higher (P < 0.05) than those from melons
      treated with the alternative spray method, which ranged from 1.8 to 2.6 log
      CFU/cm(2). Coliform counts for cantaloupes treated in the dump tank were 0.2 to
      2.2 log CFU/cm(2) and were below the detection level (-6.0 log CFU/cm(2)) on
      cantaloupes treated by the spray method. Growth of E. coli was observed in 2.5%
      of the samples of cantaloupes treated in the dump tank and in none of the samples
      of cantaloupes treated by lactic acid spray (P < 0.05). These results support the
      elimination of dump tanks in cantaloupe packing operations established by the
      Mexican government for certification of firms exporting cantaloupes to the United
      States. When a sanitizer is to be applied to the product, lactic acid seems to be
      a viable option, at least for products such as cantaloupes whose quality is not
      affected by an acid wash.

PMID- 20132685
TI  - Evaluation of a direct-fed microbial product effect on the prevalence and load of
      Escherichia coli O157:H7 in feedlot cattle.
AB  - Direct-fed microbials (DFM) have been identified as potential preharvest
      interventions for the reduction of foodborne bacterial pathogens such as
      Escherichia coli O157:H7. This study evaluated the efficacy of a DFM consisting
      of Bacillus subtilis strain 166 as an antimicrobial intervention strategy for the
      reduction of prevalence and load of E. coli O157:H7 in feces and on hides of
      feedlot cattle. Cattle (n = 526) were divided among 16 feedlot pens. Half of the
      pens received the DFM, and the other half did not. Hide and fecal samples were
      collected from each animal on days 28, 63, and 84 of the feeding trial. Over the
      course of the 84-day feeding period, there were no significant differences
      observed between treatments for either hide or fecal prevalence of E. coli
      O157:H7, or for the percentage of animals that were shedding E. coli O157:H7 at
      high levels (> or =200 CFU/g) in their feces or harboring E. coli O157:H7 at high
      levels (> or =40 CFU/cm(2)) on their hides. In addition, there was no significant
      difference between the average daily gains for the treated and control groups,
      with both groups averaging 1.3 kg/day. We concluded that the DFM tested would not
      be an effective preharvest intervention against E. coli O157:H7.

PMID- 20132686
TI  - Enhanced thermal resistance of Salmonella in marinated whole muscle compared with
      ground pork.
AB  - The internal muscle environment may enhance thermal resistance of bacterial
      pathogens. Based on the migration of pathogens into whole muscle products during
      marination, the validity of current thermal inactivation models for whole muscle
      versus ground products has been questioned. Consequently, the objective of this
      work was to compare thermal resistance of Salmonella in whole muscle versus
      ground pork. Irradiated samples of whole and ground pork loin (5.5 to 7.5 g) were
      exposed to a Salmonella-inoculated (10(8) CFU/ml) marinade (eight serovar
      cocktail) for 20 min, placed in sterile brass tubes (12.7 mm diameter), sealed,
      and heated isothermally at 55, 58, 60, 62, or 63 degrees C, and surviving
      salmonellae were enumerated on Petrifilm aerobic count plates. The thermal lag
      times and initial bacterial counts were similar for both whole muscle and ground
      samples (P > 0.05), with all samples having equivalent compositions, inocula, and
      thermal histories. Heating temperature and physical state of the meat (whole
      versus ground muscle) affected Salmonella inactivation, with greater thermal
      resistance observed in whole than in ground muscle (P < 0.05). Assuming log
      linear inactivation kinetics, Salmonella was 0.64 to 2.96 times more heat
      resistant in whole muscle than in ground pork. Therefore, thermal process
      validations for pork products should also account for the physical state of the
      product to ensure microbial safety.

PMID- 20132687
TI  - Antibiotic resistance in Salmonella isolates from imported chicken carcasses in
      Bhutan and from pig carcasses in Vietnam.
AB  - The antibiotic resistance in Salmonella isolates from 400 imported chicken
      carcasses in Bhutan and from 178 pig carcasses in Vietnam were analyzed on a
      random basis against 14 antimicrobial agents. Among the poultry samples tested,
      13% were positive for Salmonella. Salmonella Enteritidis dominated with a
      prevalence of 80.7%, and 40 of the 42 isolates harbored two or more resistance
      determinants. For the 178 pigs investigated, 49.4% of the swabs and 34.8% of the
      lymph nodes were Salmonella positive. The most prevalent serotypes in lymph nodes
      were Salmonella Derby (50.0%) and Salmonella Typhimurium (27.4%). From the
      Salmonella isolates from pigs, only 6% were sensitive to the antimicrobial agents
      tested. The high resistance level of Salmonella isolates from pigs and chicken
      carcasses to different classes of antimicrobials should be emphasized and
      encourage a prudent use of these agents in animal farming, especially in pig
      production.

PMID- 20132688
TI  - Prevalence of listeria, Aeromonas, and Vibrio species in fish used for human
      consumption in Turkey.
AB  - A total of 78 raw retail fish samples from 30 freshwater and 48 marine fish were
      examined for the presence of Listeria, Aeromonas, and Vibrio species. The overall
      incidence of Listeria spp. was 30% in freshwater samples and 10.4% in marine fish
      samples. Listeria monocytogenes (44.5%) was the most commonly isolated species in
      freshwater fish, and Listeria murrayi (83.5%) was the most commonly isolated
      species in marine fish samples. Motile aeromonads were more common in marine fish
      samples (93.7%) than in freshwater fish samples (10%). Vibrio alginolyticus,
      Vibrio fluvialis, and Vibrio damsela were isolated only in marine fish samples,
      representing 40.9, 38.6, and 36.3% of Vibrio isolates, respectively. In
      freshwater and marine fish, the highest incidences of Listeria and Aeromonas were
      found in skin samples; the highest incidence of Vibrio in marine fish was found
      in gill samples. The location of Listeria spp. and L. monocytogenes in a fish was
      significantly different among freshwater fish. A high incidence of these
      bacterial pathogens was found in the brown trout (Salmo trutta) and horse
      mackerel (Trachurus trachurus). Handling of contaminated fish, cross
      contamination, or eating raw fish might pose a health hazard, especially in
      immunosuppressed individuals, elderly people, and children. This study highlights
      the importance of bacterial pathogens in fish intended for human consumption, but
      more study is needed.

PMID- 20132689
TI  - Histamine, cadaverine, and putrescine produced in vitro by enterobacteriaceae and
      pseudomonadaceae isolated from spinach.
AB  - A total of 364 bacterial isolates, obtained from spinach leaves, were assayed in
      a decarboxylase broth containing histidine, lysine, and ornithine to check their
      ability to produce biogenic amines, and then quantified by high-performance
      liquid chromatography. Among these isolates, 240 formed cadaverine, 208 formed
      putrescine, and 196 formed histamine, in widely varying amounts. They frequently
      produced more than one biogenic amine. Klebsiella pneumoniae subsp. pneumoniae
      and Morganella morganii were the main histamine producers, with mean values of
      1,600 and 2,440 mg/liter, respectively, followed by Pantoea spp. 3 (1,710
      mg/liter) and Hafnia alvei (2,500 mg/liter). Enterobacter amnigenus and
      Enterobacter cloacae produced particularly high amounts of putrescine, with mean
      values of 2,340 and 2,890 mg/liter, respectively. The strongest cadaverine
      formation was shown by Serratia liquefaciens (3,300 mg/liter), Serratia
      marcescens (3,280 mg/liter), and Stenotrophomonas maltophilia (1,000 mg/liter).

PMID- 20132690
TI  - Isolation and identification of thermo-acidophilic bacteria from orchards in
      china.
AB  - Eight strains of thermo-acidophilic bacteria have been isolated from apple
      orchards in Shaanxi Province, China. The isolated strains were identified at the
      species level by comparing 16S rRNA gene sequences. It was found that all strains
      could be assigned to two genera. The strain YL-5 belonged to Alicyclobacillus,
      and other isolates belonged to Bacillus. The enzymatic patterns by the API ZYM
      system showed very significant differences between 12 strains of Alicyclobacillus
      and 8 strains of Bacillus. The ability of guaiacol production varied among
      different strains.

PMID- 20132691
TI  - Prevalence of emetic Bacillus cereus in different ice creams in Bavaria.
AB  - In this study, 809 samples of ice cream from different sources were investigated
      by using cultural methods for the presence of presumptive Bacillus cereus.
      Isolates from culture-positive samples were examined with a real-time PCR assay
      targeting a region of the cereulide synthetase gene (ces) that is highly specific
      for emetic B. cereus strains. The samples were collected from ice cream parlors
      and restaurants that produced their own ice cream and from international
      commercial ice cream companies in different regions of Bavaria during the summer
      of 2008. Presumptive B. cereus was found in 508 (62.7%) ice cream samples
      investigated, and 24 (4.7%) of the isolates had the genetic background for
      cereulide toxin production. The level of emetic B. cereus in the positive samples
      ranged from 0.1 to 20 CFU/g of ice cream.

PMID- 20132692
TI  - Attachment of noroviruses to stainless steel and their inactivation, using
      household disinfectants.
AB  - The aims of this study were (i) to evaluate the impact of pH and relative
      humidity on the attachment of norovirus (NoV) to fomites and (ii) to evaluate the
      effectiveness of different household disinfectants on NoV attached to fomites.
      Plaque assay and/or real-time reverse transcription PCR assay were used to
      determine the amount of murine and human NoV attached to stainless steel disks,
      i.e., the amount removed by sonication in elution buffer but not by surface
      rinses with water only. An enzymatic pretreatment was used for both human and
      murine NoV before the real-time reverse transcription PCR assay to avoid
      detection of RNA associated with inactivated virus. For both murine and human
      NoV, maximum attachment was obtained after a contact time of 10 min. Attachment
      of NoV to stainless steel does not appear to be affected by pH, although murine
      NoV was less attached (<2 log units) at pH 9 and at low relative humidity (25%)
      than was human NoV (3 log units). Sodium hypochlorite (3%) was the most effective
      disinfectant, producing a greater than 3-log reduction after 10 min compared with
      less than a 1-log reduction after treatment with quaternary ammonium compounds
      and ethoxylated alcohols. Murine NoV was more sensitive than human NoV to
      disinfectants by approximately 1 to 2 log units. These results will help improve
      strategies for decontaminating surfaces harboring NoV and thus reduce the
      incidence of illness caused by these pathogens in the food sector and domestic
      environments.

PMID- 20132693
TI  - Frequent attendance in primary care: comparison and implications of different
      definitions.
AB  - BACKGROUND: The diversity of definitions of frequent attendance in the literature
      hampers comparison of their precision, validity, and associated factors. AIM: To
      examine different definitions of frequent attendance in order to identify the
      sociodemographic and clinical factors associated with frequent attendance in
      primary care, according to each definition. DESIGN OF STUDY: One-phase cross
      sectional study. SETTING: Seventy-seven primary care centres in Catalonia, Spain.
      METHOD: A total of 3815 primary care patients were interviewed between October
      2005 and March 2006. Three definitions of frequent attendance were tested: (1)
      frequent attenders as the top 25% and the top 10% consulting patients; (2)
      frequent attenders as the top 25% and the top 10% consulting patients stratified
      by age and sex; and (3) frequent attenders as the top 25% and the top 10%
      consulting patients stratified by the presence of physical/mental conditions
      (patients with only mental disorders, with only chronic physical conditions, with
      comorbid conditions, and with no condition). Multilevel logistic regressions were
      used. RESULTS: The following factors were systematically related to frequent
      attender status: being on sick leave, being born outside of Spain, reporting
      mental health problems as the main reason for consulting, and having
      arthritis/rheumatism, or bronchitis. Major depression was related to frequent
      attendance in two of the three definitions. The factor 'GP' was related to
      frequent attendance when the top decile cut-off point was used. The models with a
      10% cut-off point were more discriminative than those with a 25% cut-off point:
      the area under the receiver operating characteristic curve for models with a 25%
      cut-off and a 10% cut-off ranged between 0.71 (95% confidence interval [CI] =
      0.70 to 0.73) and 0.75 (95% CI = 0.74 to 0.77) and between 0.79 (95% CI = 0.78 to
      0.81) and 0.85 (95% CI = 0.83 to 0.86), respectively. CONCLUSION: The way
      frequent attendance is defined is of crucial importance. It is recommended that a
      more discriminative definition of frequent attendance is used (the top 10%).

PMID- 20132694
TI  - Outcome of knee injuries in general practice: 1-year follow-up.
AB  - BACKGROUND: Knee injuries may lead to pain and to functional limitations in the
      activities of daily living. Patients with knee injuries are frequently seen in
      general practice; however, the outcome and management in these patients is not
      known. AIM: To assess the outcome and management of knee injuries at 12 months'
      follow-up in general practice. DESIGN OF STUDY: A prospective observational
      cohort study with a 1-year follow-up. SETTING: Primary health care. METHOD: Adult
      patients consulting their GP after knee injury (n = 134) participated in the
      cohort. A magnetic resonance imaging scan was carried out and patients were
      diagnosed as either no lesion or an isolated meniscal tear, an isolated
      collateral or cruciate ligament lesion, or a combination. Follow-up
      questionnaires were filled in up to 12 months' follow-up. RESULTS: At 12 months'
      follow-up, 34 patients reported full recovery and 67 patients reported major
      improvement. At baseline, 37 patients (28%) were referred to physical therapy and
      17 patients (13%) were referred to secondary care. During 1 year of follow-up,
      another 21 referrals to physical therapy and 11 referrals to secondary care took
      place. The pain severity decreased the most, and the Lysholm knee score increased
      in the majority of patients during the first 3 months after injury. In total, 18
      arthroscopies were performed in 15 patients. One patient underwent an anterior
      cruciate ligament reconstruction. CONCLUSION: The vast majority of patients
      report clinically relevant recovery. There is no clear difference in outcomes
      between patients with meniscal tears or ligament lesions and patients without
      these diagnoses.

PMID- 20132695
TI  - The Hip and Knee Book: developing an active management booklet for hip and knee
      osteoarthritis.
AB  - BACKGROUND: The pain and disability of hip and knee osteoarthritis can be
      improved by exercise, but the best method of encouraging this is not known. AIM:
      To develop an evidence-based booklet for patients with hip or knee
      osteoarthritis, offering information and advice on maintaining activity. DESIGN
      OF STUDY: Systematic review of reviews and guidelines, then focus groups.
      SETTING: Four general practices in North East Wales. METHOD: Evidence-based
      messages were developed from a systematic review, synthesised into patient
      centred messages, and then incorporated into a narrative. A draft booklet was
      examined by three focus groups to improve the phrasing of its messages and
      discuss its usefulness. The final draft was examined in a fourth focus group.
      RESULTS: Six evidence-based guidelines and 54 systematic reviews were identified.
      The focus groups found the draft booklet to be informative and easy to read. They
      reported a lack of clarity about the cause of osteoarthritis and were surprised
      that the pain could improve. The value of exercise and weight loss beliefs was
      accepted and reinforced, but there was a perceived contradiction about heavy
      physical work being causative, while moderate exercise was beneficial. There was
      a fear of dependency on analgesia and misinterpretation of the message on
      hyaluranon injections. The information on joint replacement empowered patients to
      discuss referral with their GP. The text was revised to accommodate these issues.
      CONCLUSION: The booklet was readable, credible, and useful to end-users. A
      randomised controlled trial is planned, to test whether the booklet influences
      beliefs about osteoarthritis and exercise.

PMID- 20132697
TI  - Strong medicine: research, education, and patient care in general practice.

PMID- 20132698
TI  - Doctors'non-verbal behaviour in consultations: look at the patient before you
      look at the computer.

PMID- 20132699
TI  - Aches and pains in primary care: stay positive but critical.

PMID- 20132700
TI  - Are UK cancer cure rates worse than in most other European countries?

PMID- 20132701
TI  - Patients' perceptions of GP non-verbal communication: a qualitative study.
AB  - BACKGROUND: During doctor-patient interactions, many messages are transmitted
      without words, through non-verbal communication. AIM: To elucidate the types of
      non-verbal behaviours perceived by patients interacting with family GPs and to
      determine which cues are perceived most frequently. DESIGN OF STUDY: In-depth
      interviews with patients of family GPs. SETTING: Nine family practices in
      different regions of Poland. METHOD: At each practice site, interviews were
      performed with four patients who were scheduled consecutively to see their family
      doctor. RESULTS: Twenty-four of 36 studied patients spontaneously perceived non
      verbal behaviours of the family GP during patient-doctor encounters. They
      reported a total of 48 non-verbal cues. The most frequent features were tone of
      voice, eye contact, and facial expressions. Less frequent were examination room
      characteristics, touch, interpersonal distance, GP clothing, gestures, and
      posture. CONCLUSION: Non-verbal communication is an important factor by which
      patients spontaneously describe and evaluate their interactions with a GP. Family
      GPs should be trained to better understand and monitor their own non-verbal
      behaviours towards patients.

PMID- 20132702
TI  - 'A heartbeat moment': qualitative study of GP views of patients bringing health
      information from the internet to a consultation.
AB  - BACKGROUND: Government policy is to encourage self-help among patients. The
      internet is increasingly being used for health information. The literature on the
      role of the internet in the doctor-patient consultation remains sparse. AIM: To
      determine the perceived responses of GPs to internet-informed patients in
      consultations and the strategies GPs use for dealing with information from the
      internet being brought into consultations. DESIGN OF STUDY: A qualitative study
      design was used, with semi-structured interviews. SETTING: GPs based in North
      Central London. METHOD: Analysis was conducted by a multidisciplinary team of
      researchers. Participants were 11 GPs: five partners, three locums, and three
      salaried doctors; seven were white, three were Asian, and one was of Chinese
      origin. The median year of General Medical Council (GMC) registration was 1989.
      There were six women and five men; five participants worked in training
      practices. RESULTS: GPs experienced considerable anxiety in response to patients
      bringing information from the internet to a consultation but were able to resolve
      this anxiety. The study participants learned to distance themselves from their
      emotional response, and used cognitive and behavioural techniques to assist them
      in responding appropriately to patients. These techniques included buying time in
      a consultation, learning from previous consultations, and using the internet as
      an ally, by directing patients to particular websites. The importance for doctors
      of feeling valued by patients was apparent, as was the effect of the prior doctor
      patient relationship. CONCLUSION: GPs interviewed used sophisticated mechanisms
      for dealing with their emotions. GPs struggling with internet-informed patients
      can use the mechanisms described to alleviate the difficulties.

PMID- 20132703
TI  - Ear discharge in children presenting with acute otitis media: observational study
      from UK general practice.
AB  - BACKGROUND: National Institute for Health and Clinical Excellence (NICE) guidance
      to treat otitis media in older children immediately with antibiotics only if they
      have ear discharge is based on limited evidence. AIM: To determine the clinical
      significance and outcome of ear discharge in children with acute otitis media, in
      routine clinical practice. DESIGN OF STUDY: Observational cohort study of
      children with acute otitis media comparing those with and without ear discharge
      at presentation. SETTING: Primary care in East Somerset. METHOD: Two hundred and
      fifty-six children aged 6 months to 10 years were recruited from primary care.
      Clinical features and other characteristics were recorded at presentation. Follow
      up was undertaken at 2 weeks and 3 months. RESULTS: Children with otitis media
      who present with ear discharge are much more likely to be treated with
      antibiotics irrespective of age (adjusted odds ratio 15, 95% confidence interval
      [CI] = 3 to 66). Most with discharge have proven bacterial infection (58%, 95% CI
      = 42 to 72%). They have a more severe systemic illness, with higher axillary
      temperature (80% increase in odds of ear discharge for each additional degree
      centigrade, P = 0.02), pulse rate (9% increase in odds for each extra beat,
      P<0.001), and Yale score (mean 10.5 versus 9.0, P = 0.003). They may also have an
      increased likelihood of adverse outcome (adjusted odds ratio of pain at 1 week
      2.9; further episodes of acute otitis media 3.3; hearing difficulty at 3 months
      4.7; all P<0.10). CONCLUSION: Ear discharge defines a group of children with
      otitis media who are sicker and may be at higher risk of adverse outcome. NICE
      guidance to treat them with antibiotics is supported.

PMID- 20132705
TI  - Commentary. Cancer diagnosis - the role of urgent referral guidelines.

PMID- 20132704
TI  - Cancer diagnosis in primary care.
AB  - Around a quarter of those in the developed world die of cancer. Most cancers
      present to primary care with symptoms, even when there is a screening test for
      the particular cancer. However, the symptoms of cancer are also symptoms of
      benign disease, and the GP has to judge whether cancer is a possible explanation.
      Very little research examined this process until relatively recently. This review
      paper examines the process of primary care diagnosis, especially the selection of
      patients for rapid investigation. It concentrates on the four commonest UK
      cancers: breast, lung, colon, and prostate as these have been the subject of most
      recent studies.

PMID- 20132706
TI  - Suicide in later life.

PMID- 20132707
TI  - Child neglect.

PMID- 20132708
TI  - Why do we practice CPR?

PMID- 20132709
TI  - STIs in general practice.

PMID- 20132710
TI  - Salaried doctors.

PMID- 20132711
TI  - Circumcision.

PMID- 20132712
TI  - Persistent vegetative state.

PMID- 20132713
TI  - Assisted suicide.

PMID- 20132714
TI  - Stevens-Johnson syndrome secondary to oseltamivir (Tamiflu).

PMID- 20132715
TI  - Circumcision.

PMID- 20132716
TI  - Circumcision.

PMID- 20132719
TI  - Systematic risks from chloramphenicol eye drops.

PMID- 20132721
TI  - Using expert patients to deliver teaching in general practice.

PMID- 20132722
TI  - The patient's journey: living with psoriasis - the patient's perspective.

PMID- 20132723
TI  - The patient's journey: living with psoriasis - the doctors' perspective.

PMID- 20132724
TI  - Primary care in Hong Kong: a lesson about competition.

PMID- 20132726
TI  - General practice: the future teaching environment - a report on undergraduate
      primary care education in London.

PMID- 20132728
TI  - Comparison of structure, function and regulation of plant cold shock domain
      proteins to bacterial and animal cold shock domain proteins.
AB  - The cold shock domain (CSD) is among the most ancient and well conserved nucleic
      acid binding domains from bacteria to higher animals and plants. The CSD
      facilitates binding to RNA, ssDNA and dsDNA and most functions attributed to cold
      shock domain proteins are mediated by this nucleic acid binding activity. In
      prokaryotes, cold shock domain proteins only contain a single CSD and are termed
      cold shock proteins (Csps). In animal model systems, various auxiliary domains
      are present in addition to the CSD and are commonly named Y-box proteins. Similar
      to animal CSPs, plant CSPs contain auxiliary C-terminal domains in addition to
      their N-terminal CSD. Cold shock domain proteins have been shown to play
      important roles in development and stress adaptation in wide variety of
      organisms. In this review, the structure, function and regulation of plant CSPs
      are compared and contrasted to the characteristics of bacterial and animal CSPs.
      [BMB reports 2010; 43(1): 1-8].

PMID- 20132729
TI  - Differential expression of rice calmodulin promoters in response to stimuli and
      developmental tissue in transgenic tobacco plants.
AB  - The promoters of OsCaM1 and OsCaM3 were characterized after sequencing and fused
      to the reporter gene, GUS. The constructs were then transformed into the tobacco
      plant. Histochemical analysis of GUS showed different expression patterns in
      pOsCaM1::GUS and pOsCaM3:: GUS transgenic plants. The expression of pOsCaM1::GUS
      in 4- to 15-day-old seedlings in particular was observed only in the root, while
      the expression of pOsCaM3::GUS was detected in both the cotyledons and root.
      Also, pRCaM1::GUS was detected in all the tissues surrounding the root system,
      while the presence of pOsCaM3::GUS was observed in the root, except in the root
      meristem. However, in mature transgenic plants, the expression of pOsCaM1::GUS
      and OsRCaM3::GUS was scarcely detected. Under wounding stress, the GUS activity
      of pOsCaM1 and pOsCaM3 was strongly induced, and the activity of pOsCaM3
      especially, was retained for long periods. In the phloem, pOsCaM3 activity
      induced by hormone treatments and abiotic stresses was also identified. [BMB
      reports 2010; 43(1): 9-16].

PMID- 20132730
TI  - KBTBD7, a novel human BTB-kelch protein, activates transcriptional activities of
      SRE and AP-1.
AB  - In this study, a novel member of BTB-kelch proteins, named KBTBD7, was cloned
      from a human embryonic heart cDNA library. The cDNA of KBTBD7 is 3,008 bp long
      and encodes a protein product of 684 amino acids (77.2 kD). This protein is
      highly conserved in evolution across different species. Western blot analysis
      indicates that a 77 kD protein specific for KBTBD7 is wildly expressed in all
      embryonic tissues examined. In COS-7 cells, KBTBD7 proteins are localized to the
      cytoplasm. KBTBD7 is a transcription activator when fused to GAL4 DNA-binding
      domain. Deletion analysis indicates that the BTB domain and kelch repeat motif
      are main regions for transcriptional activation. Overexpression of KBTBD7 in MCF
      7 cells activates the transcriptional activities of activator protein-1 (AP-1)
      and serum response element (SRE), which can be relieved by siRNA. These results
      suggest that KBTBD7 proteins may act as a new transcriptional activator in
      mitogen-activated protein kinase (MAPK) signaling. [BMB reports 2010; 43(1): 17
      22].

PMID- 20132731
TI  - Role of cysteine at positions 67, 161 and 241 of a Bacillus sphaericus binary
      toxin BinB.
AB  - Binary toxin consisting of BinA and BinB from Bacillus sphaericus is toxic to
      mosquito larvae. BinB is responsible for specific binding to the larval gut cell
      membrane while BinA is crucial for toxicity. To investigate functional role of
      cysteine in BinB, three cysteine residues at positions 67, 161, and 241 were
      replaced by alanine or serine. Mutations at these positions did not affect
      protein production and overall structure of BinB. These cysteine residues are not
      involved in disulfide bond formation between BinB molecules. Mosquito-larvicidal
      assays revealed that C67 and C161 are essential for toxicity, whereas C241 is
      not. Mutations at C67 and C161 resulted in weaker BinA-BinB interaction. The loss
      of toxicity may be due to the reduction of interactions between BinA and BinB or
      BinB and its receptor. C67 and C161 could also play a part during conformational
      changes or internalization of the binary toxin into the target cell. [BMB reports
      2010; 43(1): 23-28].

PMID- 20132732
TI  - Expression patterns of PRDM10 during mouse embryonic development.
AB  - It is well known that PR/SET family members participate in transcriptional
      regulation via chromatin remodeling. PRDM10 might play an essential role in gene
      expression, but no such evidence has been observed so far. To assess PRDM10
      expression at various stages of mouse development, we performed
      immunohistochemistry using available PRDM10 antibody. Embryos were obtained from
      three distinct developmental stages. At E8.5, PRDM10 expression was concentrated
      in the mesodermal and neural crest populations. As embryogenesis proceeded
      further to E13.5, PRMD10 expression was mainly in mesoderm-derived tissues such
      as somites and neural crest-derived populations such as the facial skeleton. This
      expression pattern was consistently maintained to the fetal growth period E16.5
      and adult mouse, suggesting that PRDM10 may function in tissue differentiation.
      Our study revealed that PRDM10 might be a transcriptional regulator for normal
      tissue differentiation during mouse embryonic development. [BMB reports 2010;
      43(1): 29-33].

PMID- 20132733
TI  - OsAREB1, an ABRE-binding protein responding to ABA and glucose, has multiple
      functions in Arabidopsis.
AB  - Expression patterns of OsAREB1 revealed that expression of OsAREB1 gene can be
      induced by ABA, PEG and heat. Yeast one-hybrid assay demonstrated it can bind to
      ABA-responsive element (ABRE), which was found in most stress-induced genes.
      Transgenic Arabidopsis over-expressing OsAREB1 had different responses to ABA and
      glucose compared to wild-type plants, which suggest OsAREB1 might have a crucial
      role in these two signaling pathways. Further analysis indicate that OsAREB1 have
      multiple functions in Arabidopsis. First, OsAREB1 transgenic plants had higher
      resistance to drought and heat, and OsAREB1 up-regulated the ABA/stress related
      gene such as RD29A and RD29B. Second, it delayed plant flowering time by down
      regulating the expression of flowering-related genes, such as FT, SOC1, LFY and
      AP1. Due to the dates, OsAREB1 may function as a positive regulator in
      drought/heat stresses response, but a negative regulator in flowering time in
      Arabidopsis. [BMB reports 2010; 43(1): 34-39].

PMID- 20132734
TI  - Transduced PEP-1-AMPK inhibits the LPS-induced expression of COX-2 and iNOS in
      Raw264.7 cells.
AB  - AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that plays a
      central role in cellular metabolic stress. Modulation of nitric oxide (NO) and
      cyclooxygenase-2 (COX-2) is considered a promising approach for the treatment of
      inflammation and neuronal diseases. In this study, the AMPK gene was fused in
      frame with PEP-1 peptide in a bacterial expression vector to produce a PEP-1-AMPK
      fusion protein. Expressed and purified PEP-1-AMPK fusion proteins were transduced
      efficiently into macrophage Raw 264.7 cells in a time- and dose-dependent manner.
      Furthermore, transduced PEP-1-AMPK fusion protein markedly inhibited LPS-induced
      iNOS and COX-2 expression. These results suggest that the PEP-1-AMPK fusion
      protein can be used for the protein therapy of COX-2 and NO-related disorders
      such as inflammation and neuronal diseases. [BMB reports 2010; 43(1): 40-45].

PMID- 20132735
TI  - Protection of burn-induced skin injuries by the flavonoid kaempferol.
AB  - Thermal burn injury induces inflammatory cell infiltrates in the dermis and
      thickening of the epidermis. Following a burn injury, various mediators,
      including reactive oxygen species (ROS), are produced in macrophages and
      neutrophils, exposing all tissues to oxidative injury. The anti-oxidant
      activities of flavonoids have been widely exploited to scavenge ROS. In this
      study, we observed that several flavonoids-kaempferol, quercetin, fisetin, and
      chrysin-inhibit LPS-induced IL-8 promoter activation in RAW 264.7 cells. In
      contrast with quercetin and fisetin, pretreatment of kaempferol and chrysin did
      not decrease cell viability. Inflammatory cell infiltrates in the dermis and
      thickening of the epidermis induced by burn injuries in mice was relieved by
      kaempferol treatment. However, the injury was worsened by fisetin, quercetin, and
      chrysin. Expression of TNF-a induced by burn injuries was decreased by
      kaempferol. These findings suggest the potential use of kaempferol as a
      therapeutic in thermal burn-induced skin injuries. [BMB reports 2010; 43(1): 46
      51].

PMID- 20132736
TI  - Low molecular weight silk fibroin increases alkaline phosphatase and type I
      collagen expression in MG63 cells.
AB  - Silk fibroin, produced by the silkworm Bombyx mori, has been widely studied as a
      scaffold in tissue engineering. Although it has been shown to be slowly
      biodegradable, cellular responses to degraded silk fibroin fragments are largely
      unknown. In this study, silk fibroin was added to MG-63 cell cultures, and
      changes in gene expression in the MG-63 cells were screened by DNA microarray
      analysis. Genes showing a significant (2-fold) change were selected and their
      expression changes confirmed by quantitative RT-PCR and western blotting. DNA
      microarray results showed that alkaline phosphatase (ALP), collagen type-I alpha
      1, fibronectin, and transforming growth factor-beta1 expressions significantly
      increased. The effect of degraded silk fibroin on osteoblastogenic gene
      expression was confirmed by observing up-regulation of ALP activity in MG-63
      cells. The finding that small fragments of silk fibroin are able to increase the
      expression of osteoblastogenic genes suggests that controlled degradation of silk
      fibroin might accelerate new bone formation. [BMB reports 2010; 43(1): 52-56].

PMID- 20132737
TI  - Over-expression of JunB inhibits mitochondrial stress and cytotoxicity in human
      lymphoma cells exposed to chronic oxidative stress.
AB  - Activator protein-1 can induce either cell survival or death, which is controlled
      by opposing effects of different Jun members. It is generally accepted that c-Jun
      is pro-apoptotic, but that JunD is anti-apoptotic in stress-exposed cells.
      Additionally, although there are reports suggesting that JunB plays a protective
      role, its role in stress-induced apoptosis remains unclear. Here, we investigated
      the role of JunB in H(2)O(2)-induced cell death using cells that over-expressed
      the protein or were transfected with si-JunB. Inhibition of JunB expression
      accelerated H(2)O(2)-mediated loss of mitochondrial membrane potential (MMP) and
      cytotoxicity. Conversely, over-expression of JunB protein led to significant
      inhibition of the MMP loss and cell death. The increase in JunB expression also
      attenuated nuclear relocation of apoptosis-inducing factor and mitochondrial Bcl
      2 reduction that occurred following H(2)O(2) exposure. These results suggest that
      JunB can signal survival against oxidant-mediated cell death by suppressing
      mitochondrial stress. [BMB reports 2010; 43(1): 57-61].

PMID- 20132738
TI  - Inhibition of the expression on MMP-2, 9 and morphological changes via human
      fibrosarcoma cell line by 6,6'-bieckol from marine alga Ecklonia cava.
AB  - Matrix Metalloproteinases (MMPs) are a family of zinc-endopeptidases which can
      degrade extracellular matrix (ECM) components and play important roles in a
      variety of biological and pathological processes. 6,6'-bieckol isolated and
      characterized from an edible marine brown alga Ecklonia cava (EC), according to
      the comprehensive spectral analysis of MS and NMR data. Here the influence of
      6,6'-bieckol on expressions of MMPs was examined by zymography and western blot
      analysis via human fibrosarcoma cell line (HT1080). It is shown that 6,6'-bieckol
      significantly down regulated the expressions of MMP-2 and -9 in dose-dependent
      manner. The influence of 6,6'-bieckol on the cell viability and cell behavior of
      HT1080 cells were also investigated, our dates shown that it suppressed the
      migration and 3D culture in HT1080 cells. Meanwhile, we explored several signal
      pathways which may contribute to this process, and found the suppressing of MMPs
      expressions in HT1080 cells might be due to the suppression of NF-kappaB signal
      pathway. [BMB reports 2010; 43(1): 62-68].

PMID- 20132739
TI  - Health sector leadership in mitigating climate change: experience from the UK and
      NSW.
AB  - The threat to human health from climate change means that all levels of
      government and private and public agencies will need to change their current
      practices to reduce carbon emissions. The health sector will also need to respond
      and change practice. The National Health Service in the United Kingdom is
      developing a systematic and strategic approach to reduce its carbon footprint, as
      described in the recently released NHS Carbon Reduction Strategy for England. The
      work is being led by the Service's new Sustainable Development Unit. While the
      Australian health care system has not yet embraced a shared vision for carbon
      reduction, there are examples emerging of how the sector is contributing to
      reduce greenhouse gas production. Examples from two NSW area health services to
      reduce energy use and promote active transport are presented. In both countries,
      these changes are supported by new legislation and policy.

PMID- 20132740
TI  - Newborn feeding practices at the time of discharge from hospital in NSW in 2007:
      a descriptive study.
AB  - OBJECTIVES: To describe the pattern of infant feeding at discharge from care
      after birth and the characteristics of mothers who are at risk of low rates of
      breastfeeding. METHODS: Data were obtained from the NSW Midwives Data Collection
      for 2007. Information on infant feeding was obtained for babies who were alive at
      discharge from care after birth. Of 96 030 births reported, 93 505 (97.4%) were
      eligible for analysis. A descriptive analysis of factors associated with
      variations in breastfeeding was carried out. RESULTS: In 2007, 80% of babies were
      fully breastfed, 7% were partially breastfed, and 13% were not breastfed. Babies
      born to mothers with the following characteristics had relatively low rates of
      full breastfeeding: teenage mothers (69%); Aboriginal mothers (64%); mothers born
      in South-East Asia (71%), North-East Asia (72%) and Melanesia, Micronesia and
      Polynesia (74%); mothers who commenced antenatal care later than 20 weeks
      gestation (74%); mothers who smoked (67%); mothers who received general
      anaesthetic during delivery (67%); mothers who gave birth by caesarean section
      (76%); mothers living in the most socially disadvantaged areas (73%); mothers
      living in remote and very remote areas (73% and 76% respectively); and mothers of
      preterm infants (70%). CONCLUSION: There is a need to improve overall rates of
      breastfeeding initiation in NSW. Particular attention and support needs to be
      given to the groups of mothers identified in this study as having relatively low
      rates of full breastfeeding.

PMID- 20132741
TI  - Evaluation of three population health capacity building projects delivered by
      videoconferencing in NSW.
AB  - Three population health projects in falls prevention, smoking cessation and
      refugee health secured funding through the NSW Telehealth Initiative. All were
      capacity building projects delivered through live videoconferencing sessions
      between April and August 2007. Videoconferencing as a mode of delivery was
      evaluated from the perspective of those who delivered the projects. METHOD:
      Qualitative semi-structured interviews with 12 key informants explored for each
      project: the organisation and delivery of the education sessions; the utility of
      videoconferencing for delivering training programs; and the perceived potential
      to apply videoconferencing to other functions. RESULTS: The projects were all
      delivered successfully through live videoconferencing. The main benefits observed
      were: the ability to deliver training to large numbers of people across multiple
      locations within a relatively short time and for reasonable costs; and the
      ability to improve access to high quality professional development for rural and
      remote workers. Technical difficulties were minor. The support required for these
      kinds of e-learning projects to succeed were identified. CONCLUSION: The
      evaluation confirmed the value of videoconferencing as a vehicle through which
      equity of access to learning opportunities for population health workers across
      NSW can be achieved.

PMID- 20132742
TI  - Estimate of the number of Campylobacter infections in the Hunter region, NSW,
      2004-2007.
AB  - OBJECTIVES: Campylobacteriosis is not notifiable in NSW and the number of cases
      of Campylobacter disease is thus not well described. METHODS: De-identified
      campylobacteriosis records for 2004-2007 were requested from laboratories in the
      Hunter region of NSW. Based on notifying laboratory, a Salmonella notification
      weighting was applied to laboratory-confirmed campylobacteriosis cases to provide
      an overall estimate of Campylobacter disease in the area. RESULTS: The estimated
      median of the annual number of laboratory-confirmed campylobacteriosis cases was
      788 (range 700-1022). The ratio of estimated Campylobacter cases to Salmonella
      notifications was 5.5 : 1. CONCLUSION: Campylobacter infection causes
      considerable disease in the Hunter, and likely in NSW. Regular review of
      Campylobacter laboratory results may be valuable.

PMID- 20132743
TI  - Feral pig hunting: a risk factor for human brucellosis in north-west NSW?
AB  - A multi-agency investigation followed the notification of four locally acquired
      human brucellosis cases in north-west NSW. Feral pig hunting within a
      geographically discrete region was identified as the likely exposure with
      Brucella suis the suspected cause. To test whether feral pigs in the region were
      infected with Brucella, serological testing was performed on trapped feral pigs
      and testicular abscesses from condemned carcasses bound for export were cultured.
      Although no Brucella species were identified in the feral pigs tested in NSW,
      Leptospira species were. Strengthening of human surveillance and ongoing
      collaboration between animal and human health agencies is required to confirm
      that Brucella suis causes brucellosis in humans and feral pigs in north-west NSW.

PMID- 20132744
TI  - Communicable Diseases Report, NSW, September and October 2009.

PMID- 20132745
TI  - Inter- and intraobserver reliability of the COFAS end-stage ankle arthritis
      classification system.
AB  - BACKGROUND: End-stage ankle arthritis should have an appropriate classification
      to assist surgeons in the management of end-stage ankle arthritis. Outcomes
      research also requires a classification system to stratify patients
      appropriately. MATERIALS AND METHODS: Six fellowship trained foot and ankle
      surgeons met on two occasions to derive a classification system for end-stage
      ankle arthritis. A four-part classification system was designed. Four surgeons
      reviewed blinded patient profiles and radiographs on two occasions to determine
      the inter- and intraobserver reliability. RESULTS: Good interobserver reliability
      (kappa = 0.62) and intraobserver reproducibility (kappa = 0.72) was demonstrated
      for the classification system. CONCLUSION: The COFAS classification system
      appears to be a valid tool for the management and research of end-stage ankle
      arthritis.

PMID- 20132746
TI  - Simultaneous bilateral total ankle replacement using the S.T.A.R.: a case series.

PMID- 20132747
TI  - Long-term results of salvage surgery in severely injured feet.
AB  - BACKGROUND: The purpose of our study was to analyze the long-term outcome of
      salvage surgery in severely injured feet. MATERIAL AND METHODS: Clinical
      functional scores and radiographic findings were used to assess the outcome of 18
      patients (19 feet) with severe trauma to the foot treated at a tertiary teaching
      hospital from January, 1985 to October, 2005. Fourteen males and four females
      with a mean age of 35 years were studied. The mean followup period was 76 months.
      RESULTS: There was a high incidence of late complications and poor functional
      results (mean AOFAS = 68/100): chronic pain, 15 of 19 (mean analogical pain score
      3.4/10); global foot stiffness, 11 of 19 (with radiographic evidence of arthritis
      of the remaining foot joints in 13 of 19); residual deformity, 13 of 19; arterial
      venous insufficiency, 12 of 19; signs of reflex sympathetic dystrophy, seven of
      19; chronic ulcers, six of 19; and chronic osteomyelitis, two of 19. Twelve
      patients had a visible limp and only 8 of 19 returned to work. CONCLUSIONS: Five
      years after severe foot injury most patients had painful stiffness and only 40%
      returned to work. Long-term clinical-functional results of the severely injured
      foot may be disappointing.

PMID- 20132748
TI  - A clinical study of chondral-separated types of osteochondral lesions of the
      talus.
AB  - BACKGROUND: The progress of diagnostic imaging technology, including CTs, MRIs,
      and ankle arthroscopy has encouraged more detailed descriptions of osteochondral
      lesions of the talus. These lesions can vary from chondral fragments separated
      from the subchondral bone with or without bone sclerosis or cysts in the
      subchondral layers. Isolated lesions of the cartilage, defined as chondral
      separated types, as opposed to the osteochondral-separated types which were
      osteochondral fragments, were retrospectively evaluated in this study. MATERIALS
      AND METHODS: Seventy-three osteochondral lesions of the talus in 69 patients were
      treated. There were 29 chondral-separated types in 29 patients confirmed by
      examining CT, MRI, and arthroscopic findings. RESULTS: The average age at onset
      of the chondral-separated type was 30.7 years. CT findings (29 ankles) showed
      sclerosis in seven ankles, micropores in nine, honeycombs in seven, and cysts in
      six. MRI T2-weighted image findings (28 ankles) showed micro to large pore high
      signals in the subchondral layers in 18 ankles, low to high mixed signals with
      poor margins in six, and high signals on the articular surfaces in four.
      Arthroscopic findings (29 ankles) showed softening of the articular cartilage in
      two ankles, fissures in 16, bulging and fissures in six, and detachment of the
      articular cartilage in five. CONCLUSION: The onset of these lesions occurred in
      adults after bone maturity with involvement of the chondral and subchondral
      layers. Each layer seemed to have experienced different degenerative and
      reparative processes.

PMID- 20132749
TI  - Curettage of aneurysmal bone cysts of the feet.
AB  - BACKGROUND: Aneurysmal bone cysts (ABC) mainly occur in the long bones but only
      rarely in the bones of the feet. This study reviews the 25-year experience of a
      tertiary orthopaedic oncology referral center treating ABC's in the bones of the
      feet, using prospectively collected data to document their incidence, treatment
      and the outcome. MATERIALS AND METHODS: Information on the diagnosis, treatment,
      complications and outcomes were collected for all eligible patients from our
      prospectively collected database. Radiologic healing was used as our primary
      outcome measure. Cases were considered to have failed treatment if there was
      progression of the lesion that needed further treatment. RESULTS: Of 273 patients
      with ABC, 16 patients (5.9%) were found to have their lesions in the foot. There
      were ten female and six male patients, aged from 4 to 52 (mean, 18.2) years. The
      metatarsals were the most commonly affected site (44%). Curettage of the lesion
      without additional adjuvant measures (14 of 16 patients) was sufficient for the
      treatment in 11 of 14 patients (79%). This gave a recurrence rate of 21% (three
      of 14 patients) in those treated by curettage alone and 19% (three of 16
      patients) if the whole cohort is considered. CONCLUSION: Although relatively
      rare, there is no reason to assume that ABCs of the feet will respond to
      treatment or recur any differently from ABCs that occur elsewhere in the body.
      Our experience has been that surgical curettage alone is sufficient to treat most
      ABCs of the feet.

PMID- 20132750
TI  - Mid-substance peroneal tendon defects augmented with an acellular dermal matrix
      allograft.
AB  - BACKGROUND: This study evaluated an acellular dermal matrix allograft
      augmentation for chronic mid-substance peroneous longus and brevis tendon tears.
      The hypothesis was that acellular dermal matrix allograft augmentation of chronic
      longitudinal mid-substance or complete tears of both peroneal tendons provides
      sufficient initial strength to allow a rapid rehabilitation program. MATERIALS
      AND METHODS: A consecutive series of mid-substance peroneal tendon tears with
      tissue loss was prospectively evaluated with demographic data, American
      Orthopaedic Foot and Ankle Society hindfoot-ankle scores, subjective
      questionnaires, and functional tests as well as physical examination, pre
      operative radiographs, and MRIs. Surgical reconstruction consisted of direct
      tendon repair, fibular sulcus deepening, and ;;gap jumping'' tubular grafting
      augmentation using an acellular dermal matrix. A rapid rehabilitation protocol
      was followed. Eleven cases were included (9 females and 2 males). Average age was
      46 (range, 29 to 62) years. Followup was 16.9 (range, 12 to 22) months. Two
      patients had prior surgery for instability, peroneal tendon debridement, and
      repair. Four patients had previous tenodesis. RESULTS: All showed extensive
      longitudinal tearing or complete peroneal tendon rupture on MRI. The mean
      postoperative AOFAS hindfoot score was 93.5 (range, 75 to 100). Four patients had
      1 cm of calf atrophy. All patients were able to perform single-heel rise, had
      painless ankle and foot range of motion bilaterally, and eversion/inversion
      strength was within one half grade of strength of the contralateral side in all
      patients. No postoperative hindfoot varus was identified. CONCLUSION: An
      acellular dermal matrix graft provided an effective ;;gap jumping'' augmentation
      for repairs of chronic degenerative peroneal tendon tears.

PMID- 20132751
TI  - Inter- and intraobserver reliability in the radiographic evaluation of adult
      flatfoot deformity.
AB  - BACKGROUND: Adult acquired flatfoot is a complex deformity with numerous
      radiographic measurements described to define it. The purpose of this study was
      to evaluate the inter- and intraobserver reliability of six radiographic
      measurements using digital and conventional radiographs. MATERIALS AND METHODS:
      Three digital weightbearing radiographs consisting of anteroposterior, lateral,
      and hindfoot alignment views were obtained at presentation for 20 consecutive
      patients. Six radiographic measurements were made for each patient: talus/second
      metatarsal angle, calcaneal pitch angle, talus/first metatarsal angle, medial
      cuneiform/fifth metatarsal distance, tibial/calcaneal displacement, and calcaneal
      angulation. Each radiograph was evaluated on multiple occasions by a senior
      orthopaedic surgery resident, a junior orthopaedic surgery resident, and a third
      year medical student. Inter- and intraobserver reliability was determined using
      measurements made on digital radiographs. RESULTS: Interobserver reliabilities
      were 0.830 for talus/second metatarsal angle, 0.948 for calcaneal pitch angle,
      0.781 for talus/first metatarsal angle, 0.991 for medial cuneiform/fifth
      metatarsal distance, 0.870 for tibial/calcaneal displacement, and 0.834 for
      calcaneal angulation. Interobserver reliability was similar for digital and
      conventional radiographs, and intraobserver reliability increased with observer
      experience. CONCLUSION: Adult acquired flatfoot deformity is a complex condition
      that is difficult to quantify radiographically. The medial cuneiform/fifth
      metatarsal distance and the calcaneal pitch angle were found to have the highest
      interobserver reliability. Intraobserver reliability increased with observer
      experience.

PMID- 20132752
TI  - Motion of the multisegmental foot in hallux valgus.
AB  - BACKGROUND: Hallux valgus is a common condition characterized by lateral
      deviation of the large toe and medial deviation of the first metatarsal. While
      some gait analyses of patients with hallux valgus have been performed using
      plantar pressures, very little is known about the kinematics of gait in this
      population. The purpose of this study was to evaluate triplanar kinematics in
      patients with hallux valgus using a multisegmental foot model. MATERIALS AND
      METHODS: A 15-camera Vicon Motion Analysis System was used to evaluate the gait
      of 38 feet in 33 patients with mild to severe hallux valgus. The Milwaukee foot
      model was used to characterize dynamic foot and ankle kinematics and temporal
      spatial parameters. Values were compared with normal subjects. Outcomes were
      evaluated using the SF-36 assessment tool. RESULTS: Patients with hallux valgus
      showed significantly decreased velocity and stride length and prolonged stance.
      Significant alterations in gait kinematics were observed in various planes in all
      segments (hallux, forefoot, hindfoot, and tibia) of the foot and ankle,
      particularly in the ranges of motion of the hallux and the forefoot. CONCLUSION:
      The results demonstrate significantly altered kinematic and temporal-spatial
      parameters reflective of reduced ambulatory function in patients with hallux
      valgus. As reports describing multisegmental foot and ankle kinematics in this
      population are limited, this study is valuable in characterizing gait in patients
      with hallux valgus. CLINICAL RELEVANCE: A better understanding of altered gait
      dynamics of the multisegmental foot in patients with hallux valgus provides
      valuable insight on how distal pathology affects proximal segments.

PMID- 20132753
TI  - Plantar pressure and foot pain in the last trimester of pregnancy.
AB  - BACKGROUND: Back and foot pain are common complaints during pregnancy.
      Progression of symptoms is seen especially in the third trimester as the center
      of gravity (COP) is altered due to weight gain. The aim of the study was to
      evaluate plantar pressure changes and postural balance differences of pregnant
      women. MATERIAL AND METHODS: Thirty-five last trimester pregnant women with
      complaints of foot pain were included. The control group consisted of 35 non
      pregnant women who were age and body mass index (BMI) matched volunteers. All
      selected cases were overweight. Foot pain in pregnancy was measured by Visual
      analogue scale (VAS). Percentages of pressure on forefoot and hindfoot were
      measured using static pedobarography and peak pressures at forefoot, midfoot and
      hindfoot were measured using dynamic pedobarography. As a measurement of balance,
      COP sway length and width were also analyzed. RESULTS: Compared to overweight
      individuals, pregnant patients had higher forefoot pressure on the right side
      with standing and walking. Also, significant increases in contact times under the
      forefoot and longer floor contact times were found. VAS scores were correlated
      with forefoot contact times during walking. Although the sway length from COP was
      higher than controls, no significant correlation was found in sway length and
      weight gain. CONCLUSION: These data suggest that forefoot pressures increase in
      the last trimester of pregnancy during standing and walking. There is prominent
      increased postural sway in anterior-posterior direction in this period. CLINICAL
      RELEVANCE: We believe that based on the observed pressure changes, foot pain in
      pregnancy due to changes in body mass and distribution may be relieved by
      exercise and shoewear modifications.

PMID- 20132754
TI  - Stability of medial locking plate and compression screw versus two crossed screws
      for lapidus arthrodesis.
AB  - BACKGROUND: Lapidus (first metatarsocuneiform joint) arthrodesis is an
      established procedure for the management of hallux valgus. This study
      investigated the utility of fixation with a medial locking plate with adjunct
      compression screw versus fixation with two crossed screws. MATERIALS AND METHODS:
      Eight pairs of fresh-frozen human specimens were used in a matched pair test.
      Bone mineral density (BMD) was measured with peripheral quantitative computed
      tomography (pQCT). Fixation with two 4-mm-diameter crossed screws was compared
      versus a medial locking plate (X-Locking Plate 2.4/2.7; Synthes, Solothurn,
      Switzerland) with adjunct 4-mm-diameter compression screw. The specimens were
      tested in a four-point bending test. Parameters obtained were initial stiffness;
      plantar joint-line gapping after one cycle, 100 and 1000 cycles; and number of
      cycles to failure. Failure was defined as more than or equal to 3 mm plantar
      gapping. RESULTS: The groups did not differ significantly with regard to BMD (p =
      0.866) and initial stiffness (p = 0.889). The plate-and-screw construct showed
      significantly less movement during testing, and significantly (p = 0.001) more
      cycles to failure than did the crossed-screw construct. There was a significant
      correlation (crossed-screw construct: p = 0.014; plate-and-screw construct: p =
      0.010) between BMD and the number of cycles to failure. CONCLUSION: Under cyclic
      loading conditions, the construct using a medial locking plate with adjunct
      compression screw was superior to the construct using two crossed screws.
      CLINICAL RELEVANCE: The medial locking-plate technique described could help
      shorten the period of nonweightbearing and reduce the risk of non-union.

PMID- 20132755
TI  - Biomechanical comparison of blade plate and intramedullary nail fixation for
      tibiocalcaneal arthrodesis.
AB  - BACKGROUND: Tibiocalcaneal arthrodesis is an uncommon salvage procedure used for
      complex problems of the ankle and hindfoot. A biomechanical evaluation of the
      fixation constructs of this procedure has not been studied previously. The
      purpose of this study was to compare intramedullary nail to blade plate fixation
      in a deformity model in fatigue endurance testing and load to failure. MATERIALS
      AND METHODS: Nine matched pairs of fresh frozen cadaveric legs underwent
      talectomy followed by fixation with a blade plate and 6.5-mm fully threaded
      cancellous screw or an ankle arthrodesis intramedullary nail. The specimens were
      loaded to 270 N at a rate of 3 Hz for a total of 250,000 cycles, followed by
      loading to failure. RESULTS: Intramedullary nail fixation demonstrated greater
      mean stiffness throughout the fatigue endurance testing, from cycles 10 through
      250,000 (blade plate versus intramedullary nail; cycle 10, 93 +/- 34 N/mm versus
      117 +/- 40 N/mm (t = 2.33, p = 0.04); cycle 100, 89 +/- 34 N/mm versus 118 +/- 42
      N/mm (t = 3.16, p = 0.01); cycle 1000, 86 +/- 32 N/mm versus 120 +/- 45 N/mm (t =
      3.52, p = 0.01); cycle 10,000, 83 +/- 36 N/mm versus 128 +/- 50 N/mm (t = 3.80, p
      = 0.01); cycle 100,000, 82 +/- 34 N/mm versus 126 +/- 52 N/mm (t = 3.70, p =
      0.01); cycle 250,000, 80 +/- 31 N/mm versus 125 +/- 49 N/mm (t = 4.2, p = 0.003).
      There was no statistically significant difference between the intramedullary nail
      and blade plate fixation in cycle one or in load to failure; cycle 10, blade
      plate 70 +/- 38 N/mm and intramedullary nail 67 +/- 20 N/mm (t = 0.60, p = 0.56);
      load to failure, blade plate 808 +/- 193 N, IMN 1074 +/- 290 N) (p = 0.15).
      CONCLUSION: Intramedullary nail fixation was biomechanically superior to blade
      plate and screw fixation in a tibiocalcaneal arthrodesis construct. CLINICAL
      RELEVANCE: The ankle arthrodesis intramedullary nail provides greater stiffness
      for fixation in tibiocalcaneal arthrodesis, which may improve healing.

PMID- 20132756
TI  - Tibialis posterior and flexor digitorum longus rupture associated with open
      fracture of the ankle.

PMID- 20132757
TI  - Clinical tip: one stage lengthening of fourth brachymetatarsia using fibular
      autograft.

PMID- 20132758
TI  - A porcine model for arthroscopy.

PMID- 20132759
TI  - Special report: Highlights of the 25th Annual Summer Meeting of the American
      Orthopaedic Foot and Ankle Society, Vancouver, Canada, July 16-18, 2009.

PMID- 20132760
TI  - [Hopes and challenges in biomedical research].

PMID- 20132761
TI  - [Pluristratified epidermis from human embryonic stem cells].

PMID- 20132762
TI  - [Drosophila as a new model system for leukaemia].

PMID- 20132763
TI  - [Is there a novel subset of Th22 lymphocytes in the skin distinct from Th17
      lymphocytes?].

PMID- 20132764
TI  - [The trick of the meningococcus].

PMID- 20132765
TI  - [Genetic structure and human evolution in the African continent].

PMID- 20132766
TI  - [Identification of novel polarity proteins revealed the temporal regulation of
      the epithelial phenotype].

PMID- 20132767
TI  - [Dermal fibroblasts exert a key influence in the development of basal-cell skin
      cancers: the model of Gorlin syndrome].

PMID- 20132768
TI  - [Netrin-1 and stem cells, attraction or repulsion?].

PMID- 20132769
TI  - [The SOS response controls antibiotic resistance by regulating the integrase of
      integrons].

PMID- 20132770
TI  - [Endothelial microparticles, an alarm signal for the immune system?].

PMID- 20132771
TI  - [The CHC22 human clathrin heavy chain isoform, intracellular traffic of the
      glucose transporter GLUT4, and type 2 diabetes].

PMID- 20132772
TI  - [Bacterial recognition of the intestinal microbial flora: an important risk
      factor for Crohn's disease].

PMID- 20132773
TI  - [Update on RNA splicing repair: applications to beta thalassemia and other
      perspectives].

PMID- 20132775
TI  - [Circadian rhythms and systems biology].
AB  - Cellular rhythms represent a field of choice for studies in system biology. The
      examples of circadian rhythms and of the cell cycle show how the experimental and
      modeling approaches contribute to clarify the conditions in which periodic
      behavior spontaneously arises in regulatory networks at the cellular level.
      Circadian rhythms originate from intertwined positive and negative feedback loops
      controlling the expression of several clock genes. Models can be used to address
      the dynamical bases of physiological disorders related to dysfunctions of the
      mammalian circadian clock. The cell cycle is driven by a network of cyclin
      dependent kinases (Cdks). Modeled in the form of four modules coupled through
      multiple regulatory interactions, the Cdk network operates in an oscillatory
      manner in the presence of sufficient amounts of growth factor. For circadian
      rhythms and the cell cycle, as for other recently observed cellular rhythms,
      periodic behavior represents an emergent property of biological systems related
      to their regulatory structure.

PMID- 20132776
TI  - [Multiscale modeling of cardiac electrical activity].
AB  - Models of cardiac electrical activity cover a wide range of spatial scales, from
      the genesis of the ionic currents in individual cardiomyocytes to the generation
      of electrocardiograms on the torso. The level of detail that is appropriate and
      practicable depends on the problem investigated and the scope of the computations
      that are required. We briefly present three examples of modelling: the dynamics
      of the entrainment of a single cell, the impact of fibrosis on electrical
      propagation in a piece of tissue and the generation of ECG in human. In each
      case, the methods, results and limitations are discussed.

PMID- 20132777
TI  - [Molecular operation of ionotropic glutamate receptors: proteins that mediate the
      excitatory synaptic neurotransmission].
AB  - In the brain of vertebrates, glutamate receptor ion channels (iGluR) mediate fast
      neurotransmission at excitatory synapses. They exist as distinct subfamilies
      (AMPA, Kainate and NMDA) differing in their functional properties. Yet, all iGluR
      are tetramers sharing a common molecular architecture, and a common scheme
      applies for the general mechanisms of their activation, which are discussed in
      this review. The dissection of the molecular mechanisms responsible for the
      operation of iGluR explain how they match their physiological requirements and
      paves the way to new strategies for pharmacological regulations of these
      receptors. This could prove useful for the discovery of drugs of therapeutic
      interest, such as cognitive enhancers, pain killers or anti-psychotics.

PMID- 20132778
TI  - [Norovirus infections: an overview].
AB  - Noroviruses belong to the Caliciviridae family. They are a major cause of
      sporadic cases and outbreaks of gastroenteritis in all age groups, and are
      responsible for a considerable disease burden in industrialized countries.
      Noroviruses are single-stranded RNA viruses, and show great genetic diversity
      making their detection difficult. Noroviruses can be divided into 5 genogroups,
      which themselves are subdivided into genotypes. Besides chance mutations that
      occur during viral replication, the great heterogeneity observed among
      noroviruses is also due to intra and inter-genotypic recombination events between
      strains. Some of these new variants or new recombinants are frequently associated
      with new epidemic waves of gastroenteritis. Finally, it is worth pointing out
      that the discovery of mechanisms involved in NoV infections through blood antigen
      related receptors and cultivation of the first norovirus, a murine norovirus, are
      milestones in research on this virus. These advances open new promising avenues
      of research that will help to the understanding of the -pathogenicity of this
      important pathogen.

PMID- 20132779
TI  - [When a season means depression].
AB  - Although becoming more and more recognized among physicians and psychiatrists the
      etiology of seasonal affective disorder (SAD) remains unclear. Indeed, the only
      incontestable fact is the close link between the decrease in sunlight occurring
      during fall and winter and the onset of depressive symptoms. But why does this
      seasonal decrease in the amount of light trigger a depression in some individuals
      while not affecting others? Why and how has sun exposure such an impact on brain
      mood regulation? This review intends to shed some light on the main neurochemical
      hypotheses that have been advanced for the past 25 years. While several
      hypotheses have been advanced to explain SAD, the present review will focus on
      three major suspects which are: (1) melatonin due to its crucial role in
      circadian rhythms (2) serotonin which has been linked with depressive disorders
      in general and atypical symptoms and (3) catecholamine because as for serotonin,
      many data reported an implication of these neurotransmitter family in depressive
      disorders. However, similarly to other reviews about SAD, we conclude that none
      of those could explain the pathophysiology of this northern disease on its own.

PMID- 20132780
TI  - [Is macrophage polarization the Gordian knot of bacterial infections?].
AB  - Converging studies show that M1 and M2 macrophages are functionally polarized in
      response to host mediators. Gene expression profiling of macrophages reveals that
      various bacteria induce the transcriptional activity of a common host response
      that includes genes belonging to the M1 program. The microbicidal machinery of M1
      macrophages allows them to participate to the clearing of acute infections.
      However, excessive or prolonged M1 polarization can lead to tissue injury and
      contribute to pathogenesis. The so-called M2 macrophages play a critical role in
      the resolution of inflammation by producing anti-inflammatory mediators. These M2
      macrophages cover a continuum of cells with different phenotypic and functional
      properties. Different bacterial pathogens escape from clearing by manipulating
      functions of M1 macrophages. It has recently been demonstrated that specific M2
      programs induced in macrophages by bacterial pathogens are associated with the
      chronic evolution of infectious diseases.

PMID- 20132781
TI  - [Thermal lasers and skin cicatrization].
AB  - Any cutaneous damage triggers a cascade of biological effects in the skin
      responsible for re-establishing skin integrity. Wound healing is a complex
      biological process inducing dermal remodelling leading at least to a visible
      scar, and sometimes to hypertrophic or keloid scars. Recent studies suggest that
      using a laser generates a precisely defined thermal effect in the skin, improving
      the wound healing process and potentially opening the door to scarless healing.

PMID- 20132782
TI  - [Executive women under the influence? Gender, social status and psychoactive drug
      use].

PMID- 20132783
TI  - [Fire-related deaths in India: a retrospective survey].

PMID- 20132784
TI  - [Pregnancy: a high risk factor in influenza infection].
AB  - During pregnancy both mother and foetus are at increased risk of being infected
      with either pandemic or seasonal influenza viruses, and it is thus legitimate to
      implement enhanced surveillance for infection particularly with the A/H1N1v and
      discuss priority vaccine administration. We will review the alterations in
      immunologic parameters which lead to some degree of cellular immunodeficiency,
      but also in anatomic changes and pulmonary restrictions which contribute to this
      suceptibility of pregnant women to severe complications of an influenza
      infection. We also provide an update on the epidemiological data available for
      the A/H1N1v infection in this population, and discuss the benefit/risk ratio of
      treatment with the antiviral medications.

PMID- 20132788
TI  - A community-directed strategy for sustainable malaria elimination on islands:
      short-term MDA integrated with ITNs and robust surveillance.
AB  - In the Asia Pacific sites with low and unstable transmission, elimination should
      be feasible with existing tools. On Aneityum island, Vanuatu, both Plasmodium
      falciparum and Plasmodium vivax malaria were eliminated in 1991 after
      implementation of a combined intervention package, including mass drug
      administration (MDA) and insecticide-treated bed nets (ITNs), with high degree of
      community involvement. Subsequently, community-based surveillance and vector
      control measures have kept. By reviewing the experiences of the Aneityum project,
      I intended to examine the roles of community in malaria elimination. To be
      successful, the program should transfer major intervention components from the
      external donor-directed initiative to the community-directed approach. Scaling up
      of community involvement from simple participation to social participation, where
      communities involve in health planning functions is necessary from malaria
      control to malaria elimination.

PMID- 20132789
TI  - Mutation of His 834 in human anion exchanger 1 affects substrate binding.
AB  - Anion exchanger 1 (AE1 or band 3) is responsible for Cl(-)-HCO3(-) exchange on
      erythrocyte membrane. Previously, we showed that band 3 is fixed in an inward
      facing conformation by specific modification of His 834 with DEPC, resulting in a
      strong inhibition of its anion transport activity. To clarify the physiological
      role of His 834, we evaluated the sulfate transport activities of various band 3
      mutants: different mutants at His 834 and alanine mutants of peripheral residues
      around 834 (Lys 829-Phe 836) in yeast cell membranes. The K(m) values of the His
      834 mutants were 4-10 times higher than that of the wild type, while their V(max)
      values were barely lower than that of wild type. Meanwhile, the K(m) values of
      the peripheral alanine mutants were only slightly increased. These data suggest
      that His 834 is critically important for the efficient binding of sulfate anion,
      but not for the conformational change induced by substrate binding.

PMID- 20132790
TI  - Interaction of the exported malaria protein Pf332 with the red blood cell
      membrane skeleton.
AB  - Intra-erythrocytic Plasmodium falciparum malaria parasites synthesize and export
      numerous proteins into the red blood cell (RBC) cytosol, where some bind to the
      RBC membrane skeleton. These interactions are responsible for the altered
      antigenic, morphological and functional properties of parasite-infected red blood
      cells (IRBCs). Plasmodium falciparum protein 332 (Pf332) is a large parasite
      protein that associates with the membrane skeleton and who's function has
      recently been elucidated. Using recombinant fragments of Pf332 in in vitro
      interaction assays, we have localised the specific domain within Pf332 that binds
      to the RBC membrane skeleton to an 86 residue sequence proximal to the C-terminus
      of Pf332. We have shown that this region partakes in a specific and saturable
      interaction with actin (K(d)=0.60 microM) but has no detectable affinity for
      spectrin. The only exported malaria protein previously known to bind to actin is
      PfEMP3 but here we demonstrate that there is no competition for actin-binding
      between PfEMP3 and Pf332, suggesting that they bind to different target sequences
      in actin.

PMID- 20132791
TI  - Membrane simulations mimicking acidic pH reveal increased thickness and negative
      curvature in a bilayer consisting of lysophosphatidylcholines and free fatty
      acids.
AB  - Phospholipids are key components of biological membranes and their lipolysis with
      phospholipase A(2) (PLA(2)) enzymes occurs in different cellular pH environments.
      Since no studies are available on the effect of pH on PLA(2)-modified
      phospholipid membranes, we performed 50-ns atomistic molecular dynamics
      simulations at three different pH conditions (pH 9.0, 7.5, and 5.5) using a fully
      PLA(2)-hydrolyzed phosphatidylcholine (PC) bilayer which consists solely of
      lysophosphatidylcholine and free fatty acid molecules. We found that a decrease
      in pH results in lateral squeezing of the membrane, i.e. in decreased surface
      area per headgroup. Thus, at the decreased pH, the lipid hydrocarbon chains had
      larger S(CD) order parameter values, and also enhanced membrane thickness, as
      seen in the electron density profiles across the membrane. From the lateral
      pressure profiles, we found that the values of spontaneous curvature of the two
      opposing monolayers became negative when the pH was decreased. At low pH,
      protonation of the free fatty acid headgroups reduces their mutual repulsion and
      accounts for the pH dependence of all the above-mentioned properties. The altered
      structural characteristics may significantly affect the overall surface
      properties of biomembranes in cellular vesicles, lipid droplets, and plasma
      lipoproteins, play an important role in membrane fission and fusion, and modify
      interactions between membrane lipids and the proteins embedded within them.

PMID- 20132792
TI  - LC3, a microtubule-associated protein1A/B light chain3, is involved in
      cytoplasmic lipid droplet formation.
AB  - The cytoplasmic lipid droplet (LD) is one of organelles that has a neutral lipid
      core with a single phospholipid layer. LDs are believed to be generated between
      the two leaflets of the endoplasmic reticulum (ER) membrane and to play various
      roles, such as high effective energy storage. However, it remains largely unknown
      how LDs are generated and grow in the cytoplasm. We have previously shown that
      the Atg conjugation system that is essential for autophagosome formation is
      involved in LD formation in hepatocytes and cardiac myocytes. We show here that
      LC3 itself is involved in LD formation by using RNA interference (RNAi). All
      cultured cell lines examined, in which the expression of LC3 was suppressed by
      RNAi, showed reduced LD formation. Triacylglycerol, a major component of LDs, was
      synthesized and degraded in LC3 mRNA-knockdown cells as well as in control cells.
      Interestingly, potential of the bulk protein degradation in the knockdown-cells
      was also evident in the control cells. These findings indicate that LC3 is
      involved in the LD formation regardless of the bulk degradation, and that LC3 has
      two pivotal roles in cellular homeostasis mediated by autophagy and lipid
      metabolism.

PMID- 20132793
TI  - Aquaporin-8-facilitated mitochondrial ammonia transport.
AB  - Aquaporin-8 (AQP8) is a membrane channel permeable to water and ammonia. As AQP8
      is expressed in the inner mitochondrial membrane of several mammalian tissues, we
      studied the effect of the AQP8 expression on the mitochondrial transport of
      ammonia. Recombinant rat AQP8 was expressed in the yeast Saccharomyces
      cerevisiae. The presence of AQP8 in the inner membrane of yeast mitochondria was
      demonstrated by subcellular fractionation and immunoblotting analysis. The
      ammonia transport was determined in isolated mitochondria by stopped flow light
      scattering using formamide as ammonia analog. We found that the presence of AQP8
      increased by threefold mitochondrial formamide transport. AQP8-facilitated
      mitochondrial formamide transport in rat native tissue was confirmed in liver (a
      mitochondrial AQP8-expressing tissue) vs. brain (a mitochondrial AQP8 non
      expressing tissue). Comparative studies indicated that the AQP8-mediated
      mitochondrial movement of formamide was markedly higher than that of water.
      Together, our data suggest that ammonia diffusional transport is a major function
      for mitochondrial AQP8.

PMID- 20132794
TI  - Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid
      cells.
AB  - Although it is well known that an excess of iodide suppresses thyroid function
      and blood flow in vivo, the underlying molecular mechanisms are not fully known.
      The functional effect of iodide occurs at multiple steps, which include
      inhibition of sodium/iodide symporter (NIS) expression, transient block of
      organification, and inhibition of hormonal release. The vascular effect likely
      involves suppression of the vascular endothelial growth factor (VEGF) gene. In
      this report, we show that excess iodide coordinately suppresses the expression of
      the NIS and VEGF genes in FRTL-5 thyroid cells. We also demonstrate that the
      mechanism of iodide suppression of NIS gene expression is transcriptional, which
      is synergized by the addition of thyroglobulin. Based on the findings of reporter
      gene assays and electrophoretic gel mobility shift analysis, we also report two
      novel DNA binding proteins that responded specifically to iodide and modulated
      NIS promoter activity. The results suggest that excess iodide affects thyroid
      vascular function in addition to iodide uptake. This study provides additional
      insights into the mechanism of action of excess iodide on thyroid function.

PMID- 20132795
TI  - Oxidative stress-enhanced SUMOylation and aggregation of ataxin-1: Implication of
      JNK pathway.
AB  - Although the polyglutamine protein ataxin-1 is modified by SUMO at multiple
      sites, the functions of such modification or how it is regulated are still
      unknown. Here we report that SUMO-1 or Ubc9 over-expression stimulated the
      aggregation of ataxin-1 and that oxidative stress, such as hydrogen peroxide
      treatment, further enhanced SUMO conjugation and aggregation of ataxin-1.
      Accordingly, co-treatment with antioxidant N-acetyl-cysteine attenuated the
      effect of oxidative stress. Ataxin-1, which can activate c-Jun N-terminal kinase
      (JNK) pathway by itself, strongly associated with apoptosis signal-regulating
      kinase 1 (ASK1) while not interacting with JNK. Finally, treatment of JNK
      specific inhibitor caused a reduction in the oxidant-enhanced SUMOylation and
      aggregation of ataxin-1. Together these results indicate that SUMO modification
      of ataxin-1 promotes the aggregation of ataxin-1 and that oxidative stress and
      JNK pathway play roles in this process.

PMID- 20132796
TI  - Protective effect of rebamipide against celecoxib-induced gastric mucosal cell
      apoptosis.
AB  - A major clinical problem encountered with the use of non-steroidal anti
      inflammatory drugs (NSAIDs) is gastrointestinal complications. We have previously
      suggested that both decreases in prostaglandin E(2) (PGE(2)) levels and mucosal
      apoptosis are involved in the development of NSAID-produced gastric lesions and
      that this apoptosis is mediated by an increase in the intracellular Ca(2+)
      concentration and the resulting endoplasmic reticulum (ER) stress response and
      mitochondrial dysfunction. Celecoxib and rebamipide are being used clinically as
      a safer NSAID and an anti-ulcer drug, respectively. In this study, we have
      examined the effect of rebamipide on celecoxib-induced production of gastric
      lesions. In mice pre-administered with a low dose of indomethacin, orally
      administered rebamipide suppressed celecoxib-induced mucosal apoptosis and lesion
      production but did not decrease in PGE(2) levels in the stomach. Rebamipide also
      suppressed celecoxib-induced increases in intracellular Ca(2+) concentration, the
      ER stress response, mitochondrial dysfunction and apoptosis in vitro. We also
      found that rebamipide suppresses the increases in intracellular Ca(2+)
      concentration induced by an activator of voltage-dependent L-type Ca(2+) channels
      and that another blocker of this channel suppresses celecoxib-induced increases
      in intracellular Ca(2+) concentration. These results suggest that celecoxib
      activates voltage-dependent L-type Ca(2+) channels and that rebamipide blocks
      this activation, resulting in suppression of celecoxib-induced apoptosis. We
      believe that this novel activity of rebamipide may play an important role in the
      protection of gastric mucosa against the formation of celecoxib-induced lesions.

PMID- 20132798
TI  - Aluminum induces neurofilament aggregation by stabilizing cross-bridging of
      phosphorylated c-terminal sidearms.
AB  - Exposure to neurotoxin aluminum neurotoxicity is accompanied by the perikaryal
      accumulation of tangles of phosphorylated neurofilaments (NFs). We examined their
      formation and reversibility under cell-free conditions. AlCl3 induced dose
      dependent formation of NF aggregates, ultimately incorporating 100% of detectable
      NFs. The same concentration of CaCl2 induced approximately 25% of NFs to form
      longitudinal dimers and did not induce aggregation. AlCl3 induced similar
      percentages of aggregates in the presence or absence of CaCl2, and CaCl2 could
      not reduce pre-formed aggregates. CaCl(2)-induced dimers and AlCl(3)-induced
      aggregates were prevented by prior NF dephosphorylation. While CaCl(2)-induced
      dimers were dissociated by phosphatase treatment, AlCl(3)-induced aggregates were
      only reduced by approximately 50%, suggesting that aggregates may sequester
      phosphorylation sites. Since phosphatases regulate NF phosphorylation within
      perikarya, inhibition of NF dephosphorylation by aluminum would promote
      perikaryal NF phosphorylation and foster precocious phospho-dependent NF-NF
      associations. These findings are consistent with the notion that prolonged
      interactions induced among phospho-NFs by the trivalent aluminum impairs axonal
      transport and promotes perikaryal aggregation.

PMID- 20132799
TI  - Visuospatial attention deficit in patients with local brain lesions.
AB  - The disability of visuospatial attention can lead to poor volitional movement and
      functional recovery in patients with brain lesions. However, the accurate
      clinical method to assess visuospatial attention is limited. The frontoparietal
      network including the posterior parietal cortex and the frontal eye fields has
      been shown to involve in visuospatial attention. The Attention Network Test
      provided measures for three different components of visuospatial attention:
      alerting, orienting and executive control. This study was to probe the deficit
      and relationship of visuospatial attention using Attention Network Test paradigm
      in patients with frontoparietal network lesions. During this task, patients
      responded significantly slower on each cue condition and target type than
      controls, and showed deficits in the alerting and orienting networks. The
      efficiency of resolving conflict was decreased in patients with frontal lesions
      whereas this was increased in patients with parietal lesions. These findings
      suggest that the frontoparietal network is involved in the alerting and orienting
      attentional function and the executive function is possibly selectively
      associated with the frontal lobe. The Attention Network Test paradigm produces
      sensitive, valid and reliable subject estimates of visuospatial attention
      function in patients with brain lesions, and may be useful for clinical
      rehabilitation strategy selection for patients with the frontoparietal network
      lesions.

PMID- 20132800
TI  - Peroxisome proliferator-activated receptor gamma agonist rosiglitazone attenuates
      oxyhemoglobin-induced Toll-like receptor 4 expression in vascular smooth muscle
      cells.
AB  - Inflammation and immune response have been implicated in the pathogenesis of
      cerebral vasospasm after subarachnoid hemorrhage (SAH). Recently, increased TLR4
      expression has been associated with the development of cerebral vasospasm in a
      rabbit model of SAH. Peroxisome proliferator-activated receptor gamma (PPARgamma)
      agonists, effective inhibitors of TLR4 activation, may modulate the vasospasm
      progression via their anti-inflammation effects. We investigate whether the blood
      component oxyhemoglobin (OxyHb) can induce the expression of Toll-like receptor
      (TLR) 4 in vascular smooth muscle cells (VSMCs), and evaluate the modulatory
      effects of PPARgamma agonist rosiglitazone on OxyHb-induced inflammation in
      VSMCs. Cultured VSMCs incubated with or without rosiglitazone were exposed to
      OxyHb at 10muM for up to 48h. Expression of TLR4 was assessed by
      immunocytochemistry and Western blot analysis. Production of tumor necrosis
      factor alpha (TNF-alpha) in conditioned medium were quantified by ELISA. A marked
      increase of TLR4 production and TNF-alpha release was observed at 48h after cells
      were treated with OxyHb. Rosiglitazone reduced TLR4 immunocytochemistry staining
      and protein production significantly in VSMCs. A specific antagonist for
      PPARgamma, GW9662, could reverse the anti-inflammatory effects of rosiglitazone.
      The results demonstrated that OxyHb exposure could induce TLR4 activation in
      cultured VSMCs. Rosiglitazone suppressed TLR4 expression and cytokine release via
      the activation of PPARgamma and may have a therapeutic potential for the
      treatment of vasospasm following SAH.

PMID- 20132801
TI  - Knowing where we're heading--when nothing moves.
AB  - Past research indicates that observers rely strongly on flow-based and object
      based motion information for determining egomotion or direction of heading. More
      recently, it has been shown that they also rely on displacement information that
      does not induce motion perception. As yet, little is known regarding the specific
      displacement cues that are used for heading estimation. In Experiment 1a, we show
      that the accuracy of heading estimates increases, as more displacement cues are
      available. In Experiments 1b and 2, we show that observers rely mostly on the
      displacement of objects and geometric cues for estimating heading. In Experiment
      3, we show that the accuracy of detecting changes in heading when displacement
      cues are used is low. The results are interpreted in terms of two systems that
      may be available for estimating heading, one relying on movement information and
      providing navigational mechanisms, the other relying on displacement information
      and providing navigational planning and orienting mechanisms.

PMID- 20132802
TI  - Altered spontaneous neuronal activity of the default-mode network in mesial
      temporal lobe epilepsy.
AB  - Increasing evidence from behavioral and neuroimaging studies suggests that mesial
      temporal lobe epilepsy (mTLE) is possibly associated with the default-mode brain
      function. However, the alteration of coherent neural activities in such a default
      mode network (DMN) in mTLE has yet to be investigated. The present study analyzed
      the resting-state functional MRI data from two groups of mTLE patients with left
      and right hippocampal sclerosis using independent component analysis. In
      comparison with healthy controls, decreased functional connectivity in the dorsal
      mesial prefrontal cortex, mesial temporal lobe and inferior temporal cortex was
      observed in these two patient groups. Moreover, the right but not left mTLE
      patients showed bilaterally decreased functional connectivity in the mesial
      temporal lobe and increased functional connectivity in the posterior cingulate
      cortex. The decreased functional connectivity of the mesial temporal lobe was
      related to the epilepsy duration, suggesting that the posterior cingulate cortex
      may play a compensatory role for the altered DMN in the right mTLE. These
      findings indicate that the DMN is widely affected even if a single network node
      is impaired. An extensive regional overlap between the DMN and the previously
      described epileptic network suggests that the widespread functional impairments
      in mTLE may attribute to an aberrant DMN. The distinct patterns of the DMN
      between the left and right mTLE support a view that there are different
      pathological mechanisms underlying these two types of epilepsies.

PMID- 20132803
TI  - Cytochrome P450 1A1 gene regulation by UVB involves crosstalk between the aryl
      hydrocarbon receptor and nuclear factor kappaB.
AB  - UVB induces the expression of genes controlled by the aryl hydrocarbon receptor
      (AhR), a transcription factor that has been implicated in the UV stress response.
      In this study, we used the human hepatoma cell line HepG2 to investigate in more
      detail the effects of UVB irradiation on AhR activation and induction of
      cytochrome P450 1A1 (CYP1A1), a highly AhR-responsive gene. The CYP1A1 enzyme
      efficiently degrades 6-formylindolo[3,2-b]carbazole (FICZ), a high affinity
      ligand and suggested endogenous activator of the AhR. We show that
      physiologically relevant doses of UVB suppress CYP1A1 gene expression immediately
      after irradiation, but induce its expression later in an AhR-dependent manner.
      The initial repression phase of CYP1A1 transcription was mediated by another UVB
      inducible transcription factor, the nuclear factor kappaB (NFkappaB). Crosstalk
      between AhR and NFkappaB signaling has earlier been implicated to control CYP1A1
      expression following stimulation by xenobiotics and cytokines. Now, our findings
      clearly indicate a role of NFkappaB also in UVB-dependent AhR signaling. We also
      observed that UVB reduced the catalytic activity of the CYP1A1 enzyme. Thereby,
      UVB attenuated the clearance of FICZ, which led to prolonged AhR activation. We
      further noted that repeated irradiation with UVB or H(2)O(2) treatment shifted
      the cells into a refractory state in which AhR signaling could not be efficiently
      activated by UVB or H(2)O(2), but by ligands. Together, our results suggest that
      the NFkappaB-mediated initial suppression of CYP1A1 as well as the
      unresponsiveness of AhR signaling to repeated irradiation may be part of a
      protective cellular UV stress response.

PMID- 20132804
TI  - Nitrosative stress induces osteoblast apoptosis through downregulating MAPK
      mediated NFkappaB/AP-1 activation and subsequent Bcl-X(L) expression.
AB  - During inflammation, a large amount of reactive oxygen species is produced and
      causes insults to osteoblasts. This study was aimed to evaluate the molecular
      mechanisms of sodium nitroprusside (SNP)-induced insults to rat osteoblasts.
      Exposure of osteoblasts, prepared from neonatal rat calvaria to SNP increased the
      levels of cellular nitric oxide and intracellular reactive oxygen species, and
      simultaneously induced apoptotic insults in concentration- or time-dependent
      manners. Exposure of rat osteoblasts to SNP time-dependently decreased
      antiapoptotic Bcl-X(L) messenger RNA and protein syntheses. Treatment of rat
      osteoblasts with SNP decreased the translocation of transcription factors nuclear
      factor-kappaB (NFkappaB) and activator protein (AP)-1 from the cytoplasm to
      nuclei. Sequentially, phosphorylations of the mitogen-activated protein kinases
      (MAPKs) of ERK1/2, JNK1/2, and p38 MAPK decreased following SNP administration.
      Application of ERK1 and JNK1 small interference (si)RNAs into rat osteoblasts
      decreased the translation of these MAPKs and synergistically enlarged SNP-caused
      alterations in Bcl-X(L) mRNA expression and cell apoptosis. Therefore, this study
      shows that the SNP-induced nitrosative stress decreased Bcl-X(L) expression, and
      then induced apoptotic insults to rat osteoblasts through downregulating
      phosphorylation of MAPKs and subsequent activation of NFkappaB and AP-1.

PMID- 20132805
TI  - Effect of cholesterol content on affinity and stability of factor VIII and
      annexin V binding to a liposomal bilayer membrane.
AB  - To investigate the effect of cholesterol composition on the binding of factor
      VIII (FVIII) and annexin V (AV) to membranes, liposomal membranes with
      phospholipid bilayers of various compositions of phosphatidylcholine (PC),
      phosphatidylserine (PS), and cholesterol were constructed. A surface plasmon
      resonance (SPR) biosensor system was employed to measure the equilibrium and rate
      constants of the bindings. As expected, PS was found to play a dominant role in
      the binding of AV; its binding level was directly proportional to the PS
      composition in a liposome. The binding levels of FVIII and AV to liposome
      increased with an increase in cholesterol composition in liposome. It seemed to
      suggest that cholesterol in liposome acts as a 'phospholipid arrangement' factor
      by inducing the formation of PS-rich microdomains. However, in the absence of PS
      (20% on a mole basis), cholesterol could not exert the binding enhancement
      effect, which again confirmed the critical role of PS in the bindings. Stability
      of the AV binding was significantly improved by the increase in cholesterol
      content; for AV, the dissociation rate constant was decreased approximately
      fivefold, from 1.7 x 10(-3)s(-1) in the absence of cholesterol to 3.3 x 10(-4)s(
      1) in the presence of only 10% cholesterol. But, for FVIII the binding stability
      was not so much influenced by the cholesterol addition (up to 50% on a mole
      basis). In summary, by using liposomes on an SPR system, we were able to
      demonstrate quantitatively the apparent effects of cholesterol on the binding
      affinity and stability of the membrane-binding proteins.

PMID- 20132806
TI  - Study of TNFalpha -308G/A and IL6 -174G/C polymorphisms in type 2 diabetes and
      obesity risk in the Tunisian population.
AB  - OBJECTIVES: We investigated two genetic markers in pro inflammatory molecules :
      TNFalpha -308G/A and IL6 -174G/C in order to assess their effect on type 2
      diabetes (T2D) and obesity in the Tunisian population. DESIGN AND METHODS: The
      study sample includes 228 patients with T2D and 300 healthy controls. Genotyping
      of IL6 -174G/C (rs1800795) was performed using Automated Dye Terminator
      Sequencing and of TNFalpha -308G/A (rs1800629) using the LightTyper technology.
      RESULTS: SNPs IL6 -174G/C and TNFalpha -308G/A are associated neither with T2D
      (p=0.89, p=0.34 respectively) nor with risk for overweight (p=0.86, p=0.12
      respectively) in Tunisian population. Bonferroni correction showed that the
      founded association of IL6 -174G/C SNP with T2D susceptibility restricted to
      overweight patients (p(nominal)=0.03, p(corrected)=0.0033) is likely to be a
      random result. CONCLUSION: SNPs IL6 -174G/C and TNFalpha -308G/A are not major
      contributors to T2D or obesity risk in our Tunisian population.

PMID- 20132807
TI  - Prognostic significance of adipocytokines and extracellular matrix activity in
      heart failure patients with high B-type natriuretic peptide.

PMID- 20132808
TI  - Proteolytic events in cryonecrotic cell death: Proteolytic activation of
      endonuclease P23.
AB  - Although cryosurgery is attaining increasing clinical acceptance, our
      understanding of the mechanisms of cryogenic cell destruction remains incomplete.
      While it is generally accepted that cryoinjured cells die by necrosis, the
      involvement of apoptosis was recently shown. Our studies of liver cell death by
      cryogenic temperature revealed the activation of endonuclease p23 and its de novo
      association with the nuclear matrix. This finding is strongly suggestive of a
      programmed-type of cell death process. The presumed order underlying cryonecrotic
      cell death is addressed here by examining the mechanism of p23 activation. To
      that end, nuclear proteins that were prepared from fresh liver, which is devoid
      of p23 activity, were incubated with protein fractions isolated from liver
      exposed to freezing/thawing that possessed a presumed p23 activation factor. We
      observed that the activation of p23 was the result of a proteolytic event in
      which cathepsin D played a major role. Different patterns of proteolytic cleavage
      of nuclear proteins after in vitro incubation of nuclei and in samples isolated
      from frozen/thawed liver were observed. Although both processes induced p23
      activation, the incubation experiments generated proteolytic hallmarks of
      apoptosis, while freezing/thawing of whole liver resulted in typical necrotic
      PARP-1 cleavage products and intact lamin B. As an explanation we offer a
      hypothesis that after freezing, cells possess the potential to die through
      necrotic as well as apoptotic mechanisms, based on our finding that the cytosol
      of cells exposed to cryogenic temperatures contains both necrotic and apoptotic
      executors of cell death.

PMID- 20132809
TI  - Dietary supplementation of resveratrol attenuates chronic colonic inflammation in
      mice.
AB  - Ulcerative colitis is a nonspecific inflammatory disorder characterized by
      oxidative and nitrosative stress, leucocyte infiltration and upregulation of
      inflammatory mediators. Resveratrol is a polyphenolic compound found in grapes
      and wine, with multiple pharmacological actions, mainly anti-inflammatory,
      antioxidant, antitumour and immunomodulatory activities. The aim of this study
      was to investigate the effect of dietary resveratrol on chronic dextran sulphate
      sodium (DSS)-induced colitis. Six-week-old mice were randomized into two dietary
      groups: one standard diet and the other enriched with resveratrol at 20mg/kg of
      diet. After 30days, mice were exposed to 3% DSS for 5days developing acute
      colitis that progressed to severe chronic inflammation after 21days of water. Our
      results demonstrated that resveratrol group significantly attenuated the clinical
      signs such as loss of body weight, diarrhea and rectal bleeding improving results
      from disease activity index and inflammatory score. Moreover, the totality of
      resveratrol-fed animals survived and finished the treatment while animals fed
      with standard diet showed a mortality of 40%. Three weeks after DSS removal, the
      polyphenol caused substantial reductions of the rise of pro-inflammatory
      cytokines, TNF-alpha and IL-1beta and an increase of the anti-inflammatory
      cytokine IL-10. Also resveratrol reduced prostaglandin E synthase-1 (PGES-1),
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins
      expression, via downregulation of p38, a mitogen-activated protein kinases (MAPK)
      signal pathway. We conclude that resveratrol diet represents a novel approach to
      the treatment of chronic intestinal inflammation.

PMID- 20132810
TI  - Phosphodiesterase 7A inhibitor ASB16165 impairs proliferation of keratinocytes in
      vitro and in vivo.
AB  - Excessive proliferation of epidermal keratinocytes is a typical aspect of chronic
      skin diseases such as psoriasis. In the present study, the effect of
      phosphodiesterase 7A (PDE7A) inhibitor ASB16165 on proliferation of keratinocytes
      was investigated to examine the role of PDE7A in keratinocyte proliferation and
      the possible therapeutic relevance of PDE7A inhibition in psoriasis. Topical
      application of ASB16165 inhibited the increase of thickness of skin as well as
      epidermis in a skin inflammation model induced by repeated painting of 12-O
      tetradecanoylphorbol-13-acetate (TPA) in a concentration-dependent manner. The
      ASB16165 treatment also suppressed the increase in the number of Ki67-positive
      keratinocytes in the model, showing the disturbance of keratinocyte proliferation
      by the treatment. In addition, both ASB16165 and dibutyryl cAMP significantly
      decreased the proliferation of human keratinocytes in vitro, suggesting that
      PDE7A participates in keratinocyte proliferation probably by controlling
      intracellular cAMP, while the contribution of other mechanism(s) is not
      completely denied. The findings in the present study indicate that the effect of
      ASB16165 on skin and epidermal hyperplasia in the TPA-induced skin inflammation
      is mediated, at least in part, by the inhibition of keratinocyte proliferation.
      The inhibitors for PDE7A including ASB16165 might be useful for the treatment of
      psoriasis.

PMID- 20132811
TI  - Corticotropin-releasing factor receptors and urocortins, links between the brain
      and the heart.
AB  - Corticotropin-releasing factor (CRF), a 41 amino acid peptide, was discovered as
      a key signal in mediating neuroendocrine, autonomic, and behavioral responses to
      stress. It was revealed later that there exist additional CRF-like peptides,
      termed urocortins. The CRF receptor subtype 1 (CRF1 receptor) is predominant in
      the brain whereas subtype 2 (CRF2 receptor) is highly expressed in the brain and
      the heart. Both centrally and peripherally administered CRF and urocortins
      produce significant hemodynamic effects via activation of CRF receptors in the
      brain and the heart. CRF and urocortins are important neural and cardioactive
      hormones, and are potentially useful therapy for heart failure.

PMID- 20132812
TI  - Intestinal alkaline phosphatase contributes to the reduction of severe intestinal
      epithelial damage.
AB  - Inflammatory bowel disease is characterized by chronic inflammation of the
      intestine and is accompanied by damage of the epithelial lining and by undesired
      immune responses towards enteric bacteria. It has been demonstrated that
      intestinal alkaline phosphatase (iAP) protects against the induction of
      inflammation, possibly due to dephosphorylation of lipopolysaccharide (LPS). The
      present study investigated the therapeutic potential of iAP in intestinal
      inflammation and epithelial damage. Intestinal epithelial damage was induced in
      C57BL/6 mice using detran sulfate sodium (DSS) and iAP was administered 4days
      after initial DSS exposure. Loss in body weight was significantly less in iAP
      treated mice and accompanied with reduced colon damage (determined by combination
      of crypt loss, loss of goblet cells, oedema and infiltrations of neutrophils).
      Treatment with iAP was more effective in case of severe inflammation compared to
      situations of mild to moderate inflammation. Rectal administration of LPS into a
      moderate inflamed colon did not aggravate inflammation. Furthermore, soluble iAP
      did not lower LPS-induced nuclear factor-kappaB activation in epithelial cells in
      vitro but induction of cellular AP expression by butyrate resulted in decreased
      LPS response. In conclusion, the present study shows that oral iAP administration
      has beneficial effects in situations of severe intestinal epithelial damage,
      whereas in moderate inflammation endogenous iAP may be sufficient to counteract
      disease-aggravating effects of LPS. An approach including iAP treatment holds a
      therapeutic promise in case of severe inflammatory bowel disease.

PMID- 20132813
TI  - KR-003048, a potent, orally active inhibitor of p38 mitogen-activated protein
      kinase.
AB  - The tumor necrosis factor-alpha (TNF-alpha) cytokine, secreted by activated
      monocytes/macrophages and T lymphocytes, is implicated in several diseases,
      including rheumatoid arthritis, chronic obstructive pulmonary disease,
      inflammatory bowel disease, and osteoporosis. Monocyte/macrophage production of
      TNF-alpha is largely driven by p38alpha mitogen-activated protein kinase (MAP
      kinase), an intracellular soluble serine-threonine kinase. p38alpha MAP kinase is
      activated by growth factors, cellular stresses, and cytokines such as TNF-alpha
      and interleukin-l (IL-I). The primary contribution of p38alpha activation to
      excess TNF-alpha in settings of both chronic and acute inflammation has
      instigated efforts to find inhibitors of this enzyme as possible therapies for
      associated disease states. Analogue design, synthesis, and structure-activity
      studies led to the identification of 5-tert-butyl-N-cyclopropyl-2-methoxy-3-{2-[4
      (2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-2-oxo-acetylamino}-benzamide (KR
      003048) as a potent inhibitor of the p38 MAP kinase signaling pathway in vitro
      and in vivo. The inhibition in vitro of human p38alpha enzyme activity and
      lipopolysaccharide (LPS)-induced p38 activation and subsequent TNF-alpha release
      is described. KR-00348 was demonstrated to be a potent inhibitor of inflammatory
      cytokine production ex vivo in rat and human whole blood, and showed good oral
      bioavailability. Additionally, efficacy in mouse and rat models of acute and
      chronic inflammation was obtained. KR-003048 possessed therapeutic activity in
      acute models, demonstrating substantial inhibition of carrageenan-induced paw
      edema and in vivo LPS-induced TNF release at 30mg/kg p.o. Collagen-induced
      arthritis in mice was significantly inhibited by 10 and 30mg/kg doses of KR
      003048. Evidence for disease-modifying activity in this model was indicated by
      histological evaluation of joints.

PMID- 20132814
TI  - Expression of Toll-like receptor 9 in bone marrow cells of myelodysplastic
      syndromes is down-regulated during transformation to overt leukemia.
AB  - Toll-like receptors (TLRs) play a crucial role in the host defense against
      invading microorganisms by recognizing pathogen-associated molecular patterns.
      Recently, a number of endogenous molecules have been reported to be ligands of
      TLRs. Some of these molecules are known to be expressed in cancer tissue and
      activate intracellular signal pathways via TLRs during cancer progression. Thus,
      in the present study, we analyzed the expression dynamics of TLRs in the bone
      marrow of myelodysplastic syndromes (MDS) during the course of transformation to
      overt leukemia (OL) using real-time RT-PCR. MDS bone marrow cells at the time of
      initial diagnosis tended to express higher levels of TLR2, TLR4 and TLR9 than
      control bone marrow cells. Among these TLRs, TLR9 exhibited a significant
      decrease of expression at the time of transformation to OL. The expression of
      TLR9 and TNF-alpha showed significant correlation in bone marrow cells from
      patients with MDS and OL. Immunohistochemically, TLR2 was mostly localized to
      neutrophils of the control and MDS bone marrow. TLR4 was observed in a subset of
      neutrophils and a few mononuclear cells in control and MDS bone marrow. In
      addition, TLR4 was weakly expressed in nearly half of immature myeloid cells of
      MDS cases. TLR9 was mainly localized to neutrophils in the control and RA bone
      marrow and strongly expressed in the immature myeloid cells of RAEB cases,
      although the blastic cells of OL cases did not express TLR9. Bone marrow cells in
      MDS exhibit frequent apoptosis, while OL cells are prone to be immortal. Thus,
      TLR9 might be associated with regulation of apoptotic/proliferative signals via
      TNF-alpha in the MDS bone marrow.

PMID- 20132815
TI  - Novel regulation and dynamics of myosin II activation during epidermal wound
      responses.
AB  - Wound healing in the skin is an important and complex process that involves 3
      dimensional tissue reorganization, including matrix and chemokine-triggered cell
      migration, paracrine signaling, and matrix remodeling. The molecular signals and
      underlying mechanisms that stimulate myosin II activity during skin wound healing
      have not been elucidated. To begin understanding the signaling pathways involved
      in the activation of myosin II in this process, we have evaluated myosin II
      activation in migrating primary human keratinocytes in response to scratch
      wounding in vitro. We report here that myosin II activation and recruitment to
      the cytoskeleton in wounded keratinocytes are biphasic. Post-wounding, a rapid
      phosphorylation of myosin II regulatory light chain (RLC) occurs with resultant
      translocation of myosin IIA to the cell cortex, far in advance of the later
      polarization and cell migration. During this acute-phase of myosin II activation,
      pharmacological approaches reveal p38-MAP kinase and cytosolic calcium as having
      critical roles in the phosphorylation driving cytoskeletal assembly. Although p38
      MAPK has known roles in keratinocyte migration, and known roles in leading-edge
      focal complex dynamics, to our knowledge this is the first report of p38-MAPK
      acting as an upstream activator of myosin II phosphorylation and assembly during
      any type of wound response.

PMID- 20132816
TI  - Effects of Aquaporin-4 on edema formation following intracerebral hemorrhage.
AB  - OBJECTIVE: Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes
      and is associated with high morbidity and mortality. To date, little is known
      about the role of AQP4 (Aquaporin-4), which is abundantly expressed in
      pericapillary astrocyte foot processes and in edema formation after intracerebral
      hemorrhage. The purpose of this study was to examine the role of AQP4 in edema
      formation after ICH by using AQP4(-/-) mice. METHODS: ICH was induced by
      microinjecting 5microl autologous whole blood into the striatum of AQP4(+/+) and
      AQP4(-/-) mice. We compared neurological deficits, brain edema contents of whole
      hemorrhagic ipsilateral hemisphere, specific gravity of brain tissue surrounding
      hematoma, Evans blue leakage and ultrastructure of brain microvessels between
      AQP4(+/+) and AQP4(-/-) mice following ICH. Histological changes were also
      detected with Nissl's staining and TUNEL staining. RESULTS: Our experiments
      showed a significant increase of AQP4 expression following ICH in AQP4(+/+) mice.
      AQP4 deletion aggravated neurological deficits and brain edema contents of whole
      hemorrhagic ipsilateral hemisphere. Besides, it also reduced the specific gravity
      of brain tissue surrounding hematoma. Moreover, it enhanced Evans blue leakage
      and ultrastructure of brain microvessel damage. Histology also showed less
      Nissl's staining and more TUNEL staining in AQP4(-/-) mice following ICH.
      CONCLUSIONS: These results suggest that AQP4 deletion increases ICH damage,
      including edema formation, blood-brain barrier damage and neuronal death/TUNEL
      positive cells. Further studies on the protective role of activated AQP4
      expression following ICH may provide useful therapeutic target for ICH-induced
      brain injury.

PMID- 20132817
TI  - Recovery of functional enzyme from amyloid fibrils.
AB  - Amyloid deposits, which accumulate in numerous diseases, are the final stage of
      multi-step protein conformational-conversion and oligomerization processes. The
      underlying molecular mechanisms are not fully understood, and particularly little
      is known about the reverse reaction. Here we show that phosphoglycerate kinase
      amyloid fibrils can be converted back into native protein. We achieved recovery
      with 60% efficiency, which is comparable to the success rate of the unfolding
      refolding studies, and the recovered enzyme was folded, stable and fully active.
      The key intermediate stages in the recovery process are fibril disassembly and
      unfolding followed by spontaneous protein folding.

PMID- 20132818
TI  - Ryanodine receptor mutations in arrhythmia: The continuing mystery of channel
      dysfunction.
AB  - Mutations in RyR2 are causative of an inherited disorder which often results in
      sudden cardiac death. Dysfunctional channel behaviour has been the subject of
      many investigations varying from single channel analysis through to complex
      animal models. This review discusses recent advances in the field, describes the
      controversy surrounding the exact consequences of RyR2 mutation and how the
      disparate data may be reconciled. This heterogeneity of function with respect to
      the effects of polymorphisms, phosphorylation, cytosolic and luminal Ca(2+) as
      well as inter-domain interactions may have important implications for the recent
      pharmaceutical therapies which have been put forward. We surmise that a
      comprehensive characterisation of mutations on a case-by-case basis may be
      beneficial for the development of specifically targeted therapies.

PMID- 20132819
TI  - Autophagy in skeletal muscle.
AB  - Muscle mass represents 40-50% of the human body and, in mammals, is one of the
      most important sites for the control of metabolism. Moreover, during catabolic
      conditions, muscle proteins are mobilized to sustain gluconeogenesis in the liver
      and to provide alternative energy substrates for organs. However, excessive
      protein degradation in the skeletal muscle is detrimental for the economy of the
      body and it can lead to death. The ubiquitin-proteasome and autophagy-lysosome
      systems are the major proteolytic pathways of the cell and are coordinately
      activated in atrophying muscles. However, the role and regulation of the
      autophagic pathway in skeletal muscle is still largely unknown. This review will
      focus on autophagy and discuss its beneficial or detrimental role for the
      maintenance of muscle mass.

PMID- 20132820
TI  - Structure of translation initiation factor 1 from Mycobacterium tuberculosis and
      inferred binding to the 30S ribosomal subunit.
AB  - The crystal structure of the free form of IF1 from Mycobacterium tuberculosis has
      been determined at 1.47 A resolution. The structure adopts the expected OB fold
      and matches the high structural conservation among IF1 orthologues. In order to
      further explore the function of Mtb-IF1, we built a model of its interaction with
      the 30S ribosomal subunit based on the crystal structure of the complex from
      Thermus thermophilus. The model suggests that several functionally important side
      chain residues undergo large movements while the rest of the protein in complex
      shows only very limited conformational change as compared to its form in
      solution.

PMID- 20132821
TI  - Insecticidal activity of recombinant avidin produced in yeast.
AB  - An expression construct encoding chicken (Gallus gallus) avidin was assembled
      from amplified fragments of genomic DNA. Recombinant, functional avidin was
      produced in Pichia pastoris, with yields of up to 80 mg/l of culture supernatant.
      The recombinant avidin had similar insecticidal activity to egg white avidin when
      assayed against larvae of a lepidopteran crop pest, cabbage moth (Mamestra
      brassicae), causing >90% reduction in growth and 100% mortality when fed in
      optimised diets at levels of 1.5 microM and 15 microM (100 ppm and 1000 ppm wet
      weight of recombinant protein). The recombinant protein was also highly toxic to
      a hemipteran pest, the pea aphid (Acyrthosiphon pisum), when fed in liquid
      artificial diet, causing 100% mortality after 4 days when present at
      concentrations > or = 3.8 microM (0.25 mg/ml, 250 ppm). Mortality was dose
      dependent, with an estimated LC(50) of 2.1 microM. Toxicity to A. pisum was
      prevented by biotin supplementation of diet. In contrast, avidin had no
      significant effects on the survival of cereal aphid (Sitobion avenae) at
      concentrations up to 30 microM in liquid diet. Analysis of genomic DNA showed
      that symbionts from both aphid species lack the ability to synthesise biotin de
      novo. Cereal aphids appear to be less sensitive to recombinant avidin in the diet
      through proteolysis of the ingested protein, which would allow recovery of bound
      biotin.

PMID- 20132822
TI  - A(3) adenosine receptor activation during reperfusion reduces infarct size
      through actions on bone marrow-derived cells.
AB  - The goal of this study was to examine whether the A(3) adenosine receptor
      (A(3)AR) agonist Cl-IB-MECA protects against myocardial ischemia/reperfusion
      injury when administered at the time of reperfusion in an in vivo mouse model of
      infarction induced by 30min of coronary occlusion and 24h of reperfusion.
      Treating B6 wild-type with Cl-IB-MECA during the reperfusion phase (100microg/kg
      i.v. bolus+0.3microg/kg/min subcutaneously via implantation of Alzet mini-osmotic
      pumps) reduced myocardial infarct size approximately 37% from 50.1+/-2.5% in
      vehicle-treated mice to 31.6+/-2.8% in Cl-IB-MECA-treated mice, and significantly
      reduced the number of leukocytes that infiltrated into the ischemic-reperfused
      myocardium. Cl-IB-MECA did not reduce infarct size or limit leukocyte
      accumulation in studies using B6 congenic A(3)AR gene "knock-out" mice or in
      chimeric mice lacking the expression of A(3)ARs in bone marrow (BM)-derived
      cells. Subsequent mechanistic studies demonstrated that Cl-IB-MECA inhibited
      migration of mouse neutrophils isolated from BM towards the chemotactic substance
      c5a in trans-well migration assays, and inhibited leukocyte migration into the
      peritoneal cavity in a mouse model of thioglycollate-induced peritonitis. We
      conclude that treating with the A(3)AR agonist Cl-IB-MECA at the time of
      reperfusion provides effective protection from ischemia/reperfusion injury in the
      heart through activation of the A(3)AR expressed in BM-derived cells, potentially
      by suppressing the robust inflammatory reaction that occurs during reperfusion
      and neutrophil-mediated tissue injury.

PMID- 20132823
TI  - Structural energetics of the adenine tract from an intrinsic transcription
      terminator.
AB  - Intrinsic transcription termination sites generally contain a tract of adenines
      in the DNA template that yields a tract of uracils at the 3' end of the nascent
      RNA. To understand how this base sequence contributes to termination of
      transcription, we have investigated two nucleic acid structures. The first is the
      RNA-DNA hybrid that contains the uracil tract 5'-rUUUUUAU-3' from the tR2
      intrinsic terminator of bacteriophage lambda. The second is the homologous DNA
      DNA duplex that contains the adenine tract 5'-dATAAAAA-3'. This duplex is present
      at the tR2 site when the DNA is not transcribed. The opening and the stability of
      each rU-dA/dT-dA base pair in the two structures are characterized by imino
      proton exchange and nuclear magnetic resonance spectroscopy. The results reveal
      concerted opening of the central rU-dA base pairs in the RNA-DNA hybrid.
      Furthermore, the stability profile of the adenine tract in the RNA-DNA hybrid is
      very different from that of the tract in the template DNA-DNA duplex. In the RNA
      DNA hybrid, the stabilities of rU-dA base pairs range from 4.3 to 6.5 kcal/mol
      (at 10 degrees C). The sites of lowest stability are identified at the central
      positions of the tract. In the template DNA-DNA duplex, the dT-dA base pairs are
      more stable than the corresponding rU-dA base pairs in the hybrid by 0.9 to 4.6
      kcal/mol and, in contrast to the RNA-DNA hybrid, the central base pairs have the
      highest stability. These results suggest that the central rU-dA/dT-dA base pairs
      in the adenine tract make the largest energetic contributions to transcription
      termination by promoting both the dissociation of the RNA transcript and the
      closing of the transcription bubble. The results also suggest that the high
      stability of dT-dA base pairs in the DNA provides a signal for the pausing of RNA
      polymerase at the termination site.

PMID- 20132824
TI  - Structure of the MADS-box/MEF2 domain of MEF2A bound to DNA and its implication
      for myocardin recruitment.
AB  - Myocyte enhancer factor 2 (MEF2) regulates specific gene expression in diverse
      developmental programs and adaptive responses. MEF2 recognizes DNA and interacts
      with transcription cofactors through a highly conserved N-terminal domain
      referred to as the MADS-box/MEF2 domain. Here we present the crystal structure of
      the MADS-box/MEF2 domain of MEF2A bound to DNA. In contrast to previous
      structural studies showing that the MEF2 domain of MEF2A is partially
      unstructured, the present study reveals that the MEF2 domain participates with
      the MADS-box in both dimerization and DNA binding as a single domain. The
      sequence divergence at and immediately following the C-terminal end of the MEF2
      domain may allow different MEF2 dimers to recognize different DNA sequences in
      the flanking regions. The current structure also suggests that the ligand-binding
      pocket previously observed in the Cabin1-MEF2B-DNA complex and the HDAC9 (histone
      deacetylase 9)-MEF2B-DNA complex is not induced by cofactor binding but rather
      preformed by intrinsic folding. However, the structure of the ligand-binding
      pocket does undergo subtle but significant conformational changes upon cofactor
      binding. On the basis of these observations, we generated a homology model of
      MEF2 bound to a myocardin family protein, MASTR, that acts as a potent
      coactivator of MEF2-dependent gene expression. The model shows excellent shape
      and chemical complementarity at the binding interface and is consistent with
      existing mutagenesis data. The apo structure presented here can also serve as a
      target for virtual screening and soaking studies of small molecules that can
      modulate the function of MEF2 as research tools and therapeutic leads.

PMID- 20132825
TI  - Mechanistic insights into ferredoxin-NADP(H) reductase catalysis involving the
      conserved glutamate in the active site.
AB  - Plant-type ferredoxin-NADP(H) reductases (FNRs) are flavoenzymes harboring one
      molecule of noncovalently bound flavin adenine dinucleotide that catalyze
      reversible reactions between obligatory one-electron carriers and obligatory two
      electron carriers. A glutamate next to the C-terminus is strictly conserved in
      FNR and has been proposed to function as proton donor/acceptor during catalysis.
      However, experimental studies of this proposed function led to contradicting
      conclusions about the role of this glutamate in the catalytic mechanism. In the
      present work, we study the titration behavior of the glutamate in the active site
      of FNR using theoretical methods. Protonation probabilities for maize FNR were
      computed for the reaction intermediates of the catalytic cycle by Poisson
      Boltzmann electrostatic calculations and Metropolis Monte Carlo titration. The
      titration behavior of the highly conserved glutamate was found to vary depending
      on the bound substrates NADP(H) and ferredoxin and also on the redox states of
      these substrates and the flavin adenine dinucleotide. Our results support the
      involvement of the glutamate in the FNR catalytic mechanism not only as a proton
      donor but also as a key residue for stabilizing and destabilizing reaction
      intermediates. On the basis of our findings, we propose a model rationalizing the
      function of the glutamate in the reaction cycle, which allows reinterpretation of
      previous experimental results.

PMID- 20132826
TI  - Structure of the human fatty acid synthase KS-MAT didomain as a framework for
      inhibitor design.
AB  - The human fatty acid synthase (FAS) is a key enzyme in the metabolism of fatty
      acids and a target for antineoplastic and antiobesity drug development. Due to
      its size and flexibility, structural studies of mammalian FAS have been limited
      to individual domains or intermediate-resolution studies of the complete porcine
      FAS. We describe the high-resolution crystal structure of a large part of human
      FAS that encompasses the tandem domain of beta-ketoacyl synthase (KS) connected
      by a linker domain to the malonyltransferase (MAT) domain. Hinge regions that
      allow for substantial flexibility of the subdomains are defined. The KS domain
      forms the canonical dimer, and its substrate-binding site geometry differs
      markedly from that of bacterial homologues but is similar to that of the porcine
      orthologue. The didomain structure reveals a possible way to generate a small and
      compact KS domain by omitting a large part of the linker and MAT domains, which
      could greatly aid in rapid screening of KS inhibitors. In the crystal, the MAT
      domain exhibits two closed conformations that differ significantly by rigid-body
      plasticity. This flexibility may be important for catalysis and extends the
      conformational space previously known for type I FAS and 6-deoxyerythronolide B
      synthase.

PMID- 20132827
TI  - A conserved protonation-induced switch can trigger "ionic-lock" formation in
      adrenergic receptors.
AB  - The mechanism of signal transduction in G-protein-coupled receptors (GPCRs) is a
      crucial step in cell signaling. However, the molecular details of this process
      are still largely undetermined. Carrying out submicrosecond molecular dynamics
      simulations of beta-adrenergic receptors, we found that cooperation between a
      number of highly conserved residues is crucial to alter the equilibrium between
      the active state and the inactive state of diffusible ligand GPCRs. In
      particular, "ionic-lock" formation in beta-adrenergic receptors is directly
      correlated with the protonation state of a highly conserved aspartic acid residue
      [Asp(2.50)] even though the two sites are located more than 20 A away from each
      other. Internal polar residues, acting as local microswitches, cooperate to
      propagate the signal from Asp(2.50) to the G-protein interaction site at the
      helix III-helix VI interface. Evolutionarily conserved differences between opsin
      and non-opsin GPCRs in the surrounding of Asp(2.50) influence the acidity of this
      residue and can thus help in rationalizing the differences in constitutive
      activity of class A GPCRs.

PMID- 20132828
TI  - Crystal structures of the solute receptor GacH of Streptomyces glaucescens in
      complex with acarbose and an acarbose homolog: comparison with the acarbose
      loaded maltose-binding protein of Salmonella typhimurium.
AB  - GacH is the solute binding protein (receptor) of the putative oligosaccharide ATP
      binding cassette transporter GacFG, encoded in the acarbose biosynthetic gene
      cluster (gac) from Streptomyces glaucescens GLA.O. In the context of the proposed
      function of acarbose (acarviosyl-1,4-maltose) as a 'carbophor,' the transporter,
      in complex with a yet to be identified ATPase subunit, is supposed to mediate the
      uptake of longer acarbose homologs and acarbose for recycling purposes. Binding
      assays using isothermal titration calorimetry identified GacH as a
      maltose/maltodextrin-binding protein with a low affinity for acarbose but with
      considerable binding activity for its homolog, component 5C (acarviosyl-1,4
      maltose-1,4-glucose-1,1-glucose). In contrast, the maltose-binding protein of
      Salmonella typhimurium (MalE) displays high-affinity acarbose binding. We
      determined the crystal structures of GacH in complex with acarbose, component 5C,
      and maltotetraose, as well as in unliganded form. As found for other solute
      receptors, the polypeptide chain of GacH is folded into two distinct domains
      (lobes) connected by a hinge, with the interface between the lobes forming the
      substrate-binding pocket. GacH does not specifically bind the acarviosyl group,
      but displays specificity for binding of the maltose moiety in the inner part of
      its binding pocket. The crystal structure of acarbose-loaded MalE showed that two
      glucose units of acarbose are bound at the same region and position as maltose. A
      comparative analysis revealed that in GacH, acarbose is buried deeper into the
      binding pocket than in MalE by exactly one glucose ring shift, resulting in a
      total of 18 hydrogen-bond interactions versus 21 hydrogen-bond interactions for
      MalE(acarbose). Since the substrate specificity of ATP-binding cassette import
      systems is determined by the cognate binding protein, our results provide the
      first biochemical and structural evidence for the proposed role of GacHFG in
      acarbose metabolism.

PMID- 20132829
TI  - Crystal structures of trypanosomal histidyl-tRNA synthetase illuminate
      differences between eukaryotic and prokaryotic homologs.
AB  - Crystal structures of histidyl-tRNA synthetase (HisRS) from the eukaryotic
      parasites Trypanosoma brucei and Trypanosoma cruzi provide a first structural
      view of a eukaryotic form of this enzyme and reveal differences from bacterial
      homologs. HisRSs in general contain an extra domain inserted between conserved
      motifs 2 and 3 of the Class II aminoacyl-tRNA synthetase catalytic core. The
      current structures show that the three-dimensional topology of this domain is
      very different in bacterial and archaeal/eukaryotic forms of the enzyme.
      Comparison of apo and histidine-bound trypanosomal structures indicates
      substantial active-site rearrangement upon histidine binding but relatively
      little subsequent rearrangement after reaction of histidine with ATP to form the
      enzyme's first reaction product, histidyladenylate. The specific residues
      involved in forming the binding pocket for the adenine moiety differ
      substantially both from the previously characterized binding site in bacterial
      structures and from the homologous residues in human HisRSs. The essentiality of
      the single HisRS gene in T. brucei is shown by a severe depression of parasite
      growth rate that results from even partial suppression of expression by RNA
      interference.

PMID- 20132830
TI  - Why do sex ratio dimorphisms exist in Quercus masting? Evolution of imperfect
      synchronous reproduction in Monoecious trees.
AB  - Masting is synchronous intermittent production of seeds in perennial plant
      populations. Some self-compatible monoecious Quercus species, such as oaks,
      exhibit sex ratio dimorphism and produce a certain proportion of male flowers,
      even in a year when no seed set occurs. To investigate sex ratio dimorphism in
      masting trees, we introduced sexual allocation as an evolutionary trait into the
      Resource Budget Model and examined the evolution of the sex ratio. Analytical and
      numerical findings show that (1) perfectly synchronous intermittent reproduction
      does not evolve; (2) if the fruiting cost of female flowers R(c) is sufficiently
      large and the pollen limitation beta is intermediate, annual reproduction does
      not evolve; (3) under conditions (2), sex ratio dimorphism can evolve across a
      wide region of parameter space; (4) after dimorphism is established, individuals
      with a female-biased sex ratio receive much more pollen supply from male-biased
      individuals and tend to show intermittent reproduction with or without synchrony;
      and (5) dimorphism is maintained with irregular and nearly discontinuous changes
      of sex ratio. These results suggest that sex ratio dimorphism contributes to
      improving pollen availability and causes resource depletion and the occurrence of
      intermittent reproduction in female-biased individuals.

PMID- 20132831
TI  - Differential engagement of brain regions within a 'core' network during scene
      construction.
AB  - Reliving past events and imagining potential future events engages a well
      established "core" network of brain areas. How the brain constructs, or
      reconstructs, these experiences or scenes has been debated extensively in the
      literature, but remains poorly understood. Here we designed a novel task to
      investigate this (re)constructive process by directly exploring how naturalistic
      scenes are built up from their individual elements. We "slowed-down" the
      construction process through the use of auditorily presented phrases describing
      single scene elements in a serial manner. Participants were required to integrate
      these elements (ranging from three to six in number) together in their
      imagination to form a naturalistic scene. We identified three distinct sub
      networks of brain areas, each with different fMRI BOLD response profiles,
      favouring specific points in the scene construction process. Areas including the
      hippocampus and retrosplenial cortex had a biphasic profile, activating when a
      single scene element was imagined and when 3 elements were combined together;
      regions including the intra-parietal sulcus and angular gyrus steadily increased
      activity from 1 to 3 elements; while activity in areas such as lateral prefrontal
      cortex was observed from the second element onwards. Activity in these sub
      networks did not increase further when integrating more than three elements.
      Participants confirmed that three elements were sufficient to construct a
      coherent and vivid scene, and once this was achieved, the addition of further
      elements only involved maintenance or small changes to that established scene.
      This task offers a potentially useful tool for breaking down scene construction,
      a process that may be key to a range of cognitive functions such as episodic
      memory, future thinking and navigation.

PMID- 20132832
TI  - Implications of animal object memory research for human amnesia.
AB  - Damage to structures in the human medial temporal lobe causes severe memory
      impairment. Animal object recognition tests gained prominence from attempts to
      model 'global' human medial temporal lobe amnesia, such as that observed in
      patient HM. These tasks, such as delayed nonmatching-to-sample and spontaneous
      object recognition, for assessing object memory in non-human primates and rodents
      have proved invaluable as animal models of specific aspects of human declarative
      memory processes. This paper reviews research in non-human primates and rats
      using object recognition memory tasks to assess the neurobiological bases of
      amnesia. A survey of this research reveals several important implications for our
      understanding of the anatomical basis of memory and the medial temporal lobe
      amnesic syndrome. First, research with monkeys and rats reveals that the
      contributions of medial temporal lobe structures such as the hippocampus and
      perirhinal cortex to memory processes are dissociable, with particular structures
      contributing to specific tasks on the basis of the specific type of information
      that a structure is optimized to process. Second, the literature suggests that
      cognitive tasks requiring integration of different types of information, such as
      in the case of complex, multimodal declarative memory, will recruit structures of
      the medial temporal lobe in an interactive manner. The heterogeneity of function
      within the medial temporal lobe, as well as the multimodal and complex nature of
      human declarative memory, implies that animal tests of object recognition memory,
      once believed to be comprehensive models for the study of human global amnesia,
      model just one important facet of human declarative memory. Finally, in light of
      the research reviewed here, it is apparent that the specific nature of amnesia
      observed in an individual with medial temporal lobe damage will depend on the
      particular medial temporal lobe regions affected and their specific
      representational capacities.

PMID- 20132833
TI  - Role of progesterone on the regulation of vascular muscle cells proliferation,
      migration and apoptosis.
AB  - The purpose of this study was to investigate the effect of progesterone (Pg) on
      cellular growth, migration, apoptosis, and the molecular mechanism of action
      displayed by the steroid. To that end, rat aortic vascular smooth muscle cell
      (VSMC) cultures were employed. Pg (10nM) significantly increased [(3)H]thymidine
      incorporation after 24h of treatment. The enhancement in DNA synthesis was
      blunted in the presence of an antagonist of Pg receptor (RU486 compound). The
      mitogenic action of the steroid was suppressed by the presence of the compounds
      PD98059 (MEK inhibitor), chelerythrine (PKC inhibitor), and indomethacin
      (cyclooxygenase antagonist) suggesting that the stimulation of DNA synthesis
      involves MAPK, PKC, and cyclooxygenase transduction pathways. The proliferative
      effect of the hormone depends on the presence of endothelial cells (EC). When
      muscle cells were incubated with conditioned media obtained of EC treated with
      Pg, the mitogenic action of the steroid declined. Wounding assays shows that 10nM
      Pg enhances VSMC migration and motility. The role of the steroid on programmed
      cell death was measured using DNA fragmentation technique. Four hours of
      treatment with 10nM Pg enhanced DNA laddering in a similarly extent to the
      apoptotic effect induced by the apoptogen hydrogen peroxide (H(2)O(2)). In
      summary the results presented provide evidence that Pg enhances cell
      proliferation, migration, and apoptosis of VSMC. The modulation of cell growth
      elicited by the steroid involves integration between genomic and signal
      transduction pathways activation.

PMID- 20132834
TI  - The effects of 3,4-methylenedioxymethamphetamine (MDMA) on nicotinic receptors:
      intracellular calcium increase, calpain/caspase 3 activation, and functional
      upregulation.
AB  - Previous work by our group demonstrated that homomeric alpha7 nicotinic
      acetylcholine receptors (nAChR) play a role in the neurotoxicity induced by 3,4
      methylenedioxymethamphetamine (MDMA), as well as the binding affinity of this
      drug to these receptors. Here we studied the effect of MDMA on the activation of
      nAChR subtypes, the consequent calcium mobilization, and calpain/caspase 3
      activation because prolonged Ca(2+) increase could contribute to cytotoxicity. As
      techniques, we used fluorimetry in Fluo-4-loaded PC12 cells and electrophysiology
      in Xenopus oocytes. MDMA produced a rapid and sustained increase in calcium
      without reaching the maximum effect induced by ACh. It also concentration
      dependently inhibited the response induced by ACh, nicotine, and the specific
      alpha7 agonist PNU 282987 with IC(50) values in the low micromolar range.
      Similarly, MDMA induced inward currents in Xenopus oocytes transfected with human
      alpha7 but not with alpha4beta2 nAChR and inhibited ACh-induced currents in both
      receptors in a concentration-dependent manner. The calcium response was inhibited
      by methyllycaconitine (MLA) and alpha-bungarotoxin but not by dihydro-beta
      erythroidine. These results therefore indicate that MDMA acts as a partial
      agonist on alpha7 nAChRs and as an antagonist on the heteromeric subtypes.
      Subsequently, calcium-induced Ca(2+) release from the endoplasmic reticulum and
      entry through voltage-operated calcium channels are also implicated as proved
      using specific antagonists. In addition, treatment with MDMA for 24 h
      significantly increased basal Ca(2+) levels and induced an increase in alpha
      spectrin breakdown products, which indicates that calpain and caspase 3 were
      activated. These effects were inhibited by pretreatment with MLA. Moreover,
      pretreatment with MDMA induced functional upregulation of calcium responses to
      specific agonists of both heteromeric and alpha7 nAChR. Sustained calcium entry
      and calpain activation could favor the activation of Ca(2+)-dependent enzymes
      such as protein kinase C and nitric oxide synthase, which are involved in the
      generation of ROS and the blockade of the dopamine transporter. This, together
      with caspase 3 activation, must play a role in MDMA-induced cytotoxicity.

PMID- 20132835
TI  - Measuring and modeling of binary mixture effects of pharmaceuticals and nickel on
      cell viability/cytotoxicity in the human hepatoma derived cell line HepG2.
AB  - The interaction of drugs and non-therapeutic xenobiotics constitutes a central
      role in human health risk assessment. Still, available data are rare. Two
      different models have been established to predict mixture toxicity from single
      dose data, namely, the concentration addition (CA) and independent action (IA)
      model. However, chemicals can also act synergistic or antagonistic or in dose
      level deviation, or in a dose ratio dependent deviation. In the present study we
      used the MIXTOX model (EU project ENV4-CT97-0507), which incorporates these
      algorithms, to assess effects of the binary mixtures in the human hepatoma cell
      line HepG2. These cells possess a liver-like enzyme pattern and a variety of
      xenobiotic-metabolizing enzymes (phases I and II). We tested binary mixtures of
      the metal nickel, the anti-inflammatory drug diclofenac, and the antibiotic agent
      irgasan and compared the experimental data to the mathematical models. Cell
      viability was determined by three different methods the MTT-, AlamarBlue(R) and
      NRU assay. The compounds were tested separately and in combinations. We could
      show that the metal nickel is the dominant component in the mixture, affecting an
      antagonism at low-dose levels and a synergism at high-dose levels in combination
      with diclofenac or irgasan, when using the NRU and the AlamarBlue assay. The dose
      response surface of irgasan and diclofenac indicated a concentration addition.
      The experimental data could be described by the algorithms with a regression of
      up to 90%, revealing the HepG2 cell line and the MIXTOX model as valuable tool
      for risk assessment of binary mixtures for cytotoxic endpoints. However the model
      failed to predict a specific mode of action, the CYP1A1 enzyme activity.

PMID- 20132836
TI  - Chronic effects of cyanobacterial toxins on Daphnia magna and their offspring.
AB  - The zooplankton grazer Daphnia magna endures living in water bodies up to
      moderate densities of cyanobacteria, such as Microcystis spp., known for
      producing toxic secondary metabolites. Although daphnids are affected via
      decreased food filtering, inhibition of digestive proteases and lethality,
      development of tolerance against cyanobacterial toxins has also been observed.
      Aim of our study was to investigate in detail chronic effects of cyanobacterial
      toxins, with emphasis on microcystin, on D. magna. The animals were exposed
      chronically for two generations to either microcystin-LR in 5 or 50 microg L(-1),
      or to cyanobacterial crude extract containing the same amount of total
      microcystin, starting at neonate stadium. Survival, growth, maturation and
      fecundity were observed for the first generation during two months. In the
      offspring survival, maturation, and growth were followed for the first week. Low
      concentration of microcystin-LR slightly affected the growth and reproduction of
      parent daphnids. Survivorship decreased during chronic exposure with increasing
      microcystin concentration. Age to maturity of the offspring increased and their
      survival decreased after parent generation was exposed to the toxin, even if the
      offspring were raised in control medium. Besides, cessation of the eggs/embryos
      was observed and malformation of neonates caused by cyanobacterial toxins was
      firstly recorded.

PMID- 20132837
TI  - Comparison of physician weight loss goals for obese male and female patients.
AB  - OBJECTIVE: The aim of this study was to compare physicians' weight loss goals for
      obese male and female patients. METHOD: This study was conducted in 2008-2009 in
      Florida, USA. Physicians (N=108; 79.6% primary care specialty) reviewed two
      hypothetical clinical scenarios that were identical with respect to health status
      and obesity (BMI=33 kg/m(2)) but differed in the gender of the patient.
      Physicians then completed a survey about the need for weight loss, intentions to
      provide weight loss counseling, and weight loss goals (i.e., ideal, successful,
      and acceptable goal weights) for each hypothetical patient. RESULTS: Physicians
      strongly agreed that both patients should lose weight and physician counseling
      and/or treatment referrals would be appropriate; however, physician weight loss
      goals for male and female patients differed. BMI values calculated from the
      suggested ideal, successful, and acceptable weight goals were significantly lower
      for female patients than male patients, 22.0 vs. 25. 2 kg/m(2); 25.4 vs. 27. 8
      kg/m(2); and 27.0 vs. 29. 2 kg/m(2), respectively, P values <.001. CONCLUSIONS:
      Physicians endorsed significantly more stringent weight loss goals for obese
      female patients than obese male patients. Regardless of patient gender, physician
      goals exceeded the 5-10% losses currently recommended. Additional research is
      needed to better understand this gender discrepancy in physician expectations for
      obese patients.

PMID- 20132838
TI  - Gateway-compatible lentiviral transfer vectors for ubiquitin promoter driven
      expression of fluorescent fusion proteins.
AB  - Lentiviral gene delivery has become widely used. Similarly, the Gateway cloning
      technology that allows restriction-independent cloning of genes into target
      vectors is becoming increasingly popular. Here, we have generated two Gateway
      compatible lentiviral transfer vectors for expression of carboxy-terminal
      fluorescence tagged fusion proteins, pLVU/GFP and pLVU/RED. We used a restriction
      enzyme-independent PCR-based approach to introduce the carboxy-terminal
      fluorescence tags, EmGFP and DsRed, respectively. Both vectors combine the
      advantages of restriction enzyme/ligation-independent cloning using the Gateway
      system with a attR1-CmR-ccdB-attR2 recombination cassette, together with
      expression of fluorescence tagged fusion proteins driven by the robust mammalian
      ubiquitin C (UbC) promoter. We tested the vectors by expressing different
      proteins together with the carboxy-terminal fluorescence tags in 293T and SH-SY5Y
      cells. Both pLVU/GFP and pLVU/RED can be utilized in different experiments,
      including protein localization studies and live-cell in vivo imaging.

PMID- 20132839
TI  - Structural simplexity of the brain.
AB  - Simplexity is an emerging concept that expresses a possible complementary
      relationship between complexity and simplicity. The brain has been known as the
      most complex structure, and tremendous effort has been spent to study how it
      works. By understanding complex function of the brain, one can hope to unravel
      the mystery of its diseases and its biological systems. We propose herein an
      entropy-based framework for analysis of complexity with a particular application
      to the study of white matter changes of the human brain. In this analysis, the
      proposed approach takes into account both morphological structure and image
      intensity values of MRI scans to construct the complexity profiles of the brain.
      It has been realized that the quantity and spatial distribution of white matter
      changes play an important role in cognitive decline (i.e. dementia) and other
      neuropsychiatric disorders (i.e. multiple sclerosis, depression) as well as in
      other dementia disorders such as Alzheimers disease. Thus, the results can be
      utilized as a tool for automated quantification and comparison of various spatial
      distributions and orientations of age-related white matter changes where manual
      analysis is difficult and leads to different sensitivities for the respective MRI
      based information of the brain.

PMID- 20132840
TI  - In vitro stability of Cucumber mosaic virus nanoparticles carrying a Hepatitis C
      virus-derived epitope under simulated gastrointestinal conditions and in vivo
      efficacy of an edible vaccine.
AB  - The Cucumber mosaic virus (CMV) is an isodiametric plant virus with an extremely
      wide host range, present worldwide. CMV chimeric particles (R9-CMV), engineered
      to express a 27-aa synthetic peptide derived from Hepatitis C virus (HCV), were
      demonstrated to be stable under simulated gastric and intestinal conditions. Then
      the possibility of inducing a humoral immune response in rabbits fed with R9-CMV
      infected lettuce plants was demonstrated, suggesting that this system could
      function as a confirming tool of a bioreactor for the production of a stable
      edible vaccine against HCV.

PMID- 20132841
TI  - The use of AlphaLISA technology to detect interaction between hepatitis C virus
      encoded NS5A and cyclophilin A.
AB  - Cyclosporine A (CsA) is an immunosuppressive molecule that also impedes
      replication of hepatitis C virus (HCV). CsA inhibits isomerase activity of
      cellular-encoded cyclophilin proteins, of which cyclophilin A (CypA) in
      particular is required for HCV replication. Evidence suggests that the HCV
      encoded NS5A and NS5B proteins may govern dependence of the virus on CypA
      mediated isomerase activity, although the molecular mechanisms involved are
      unclear. However, association of NS5A and NS5B, with CypA has been reported,
      raising the possibility that direct interaction between these proteins
      facilitates HCV replication. In the present study, mammalian two-hybrid and
      AlphaLISA technologies were utilized to detect interactions between NS5A and
      NS5B, with CypA. AlphaLISA analysis revealed associations between NS5A and CypA
      using purified proteins, and in cell lysates prepared from co-transfected cells.
      Importantly, the NS5A-CypA interactions were sensitive to CsA in a dose
      responsive manner and an isomerase mutant of CypA interacted with NS5A less
      efficiently than wild-type CypA. These findings correlate the anti-HCV properties
      of CsA with an ability of the compound to disrupt NS5A-CypA interactions in vitro
      and in vivo, whilst providing the basis for development of assay platforms
      suitable to screen compound libraries for novel inhibitors of the NS5A-CypA
      interaction.

PMID- 20132842
TI  - Structure and function of the molecular chaperone Trigger Factor.
AB  - Newly synthesized proteins often require the assistance of molecular chaperones
      to efficiently fold into functional three-dimensional structures. At first,
      ribosome-associated chaperones guide the initial folding steps and protect
      growing polypeptide chains from misfolding and aggregation. After that folding
      into the native structure may occur spontaneously or require support by
      additional chaperones which do not bind to the ribosome such as DnaK and GroEL.
      Here we review the current knowledge on the best-characterized ribosome
      associated chaperone at present, the Escherichia coli Trigger Factor. We describe
      recent progress on structural and dynamic aspects of Trigger Factor's
      interactions with the ribosome and substrates and discuss how these interactions
      affect co-translational protein folding. In addition, we discuss the newly
      proposed ribosome-independent function of Trigger Factor as assembly factor of
      multi-subunit protein complexes. Finally, we cover the functional cooperation
      between Trigger Factor, DnaK and GroEL in folding of cytosolic proteins and the
      interplay between Trigger Factor and other ribosome-associated factors acting in
      enzymatic processing and translocation of nascent polypeptide chains.

PMID- 20132843
TI  - Challenges of steroid biotransformation with human cytochrome P450 monooxygenase
      CYP21 using resting cells of recombinant Schizosaccharomyces pombe.
AB  - Since cytochrome P450 monooxygenases enable the regio- and stereo-selective
      hydroxylation of C-H bonds, they are of outstanding interest for the synthesis of
      pharmaceuticals and fine chemicals. Nevertheless, for industrial applications of
      such enzymes, e.g., steroid hydroxylation, several challenges like cofactor and
      oxygen supply, limited stability and activity, or low substrate solubility have
      to be overcome. To identify the limiting factors in a P450 catalyzed whole cell
      biotransformation, 21-hydroxylation of 17-alpha-hydroxyprogesterone in
      Schizosaccharomyces pombe expressing human CYP21 was chosen as model reaction. We
      report here that resting cells of this recombinant yeast strain can be used for
      efficient biotransformation. In the present study, we analyzed the intracellular
      redox cofactor pool of S. pombe by LC-MS/MS measurements and report the first
      quantification of the intracellular cofactor pool during P450 hydroxylation.
      Thereby a limitation caused by the redox cofactor could be excluded for resting
      cells. In contrary, low substrate solubility and its transport into the cell
      affect activity. Screening for an appropriate cosolvent identified methanol as
      the most promising candidate, since it showed the lowest inactivation effect on
      the biocatalyst. Through permeabilization of the membrane with the detergent
      tween 80 steroid hydroxylation activity increases, leading to a productivity of
      540 microM d(-1) in a final batch experiment under optimized reaction conditions.

PMID- 20132844
TI  - Identification of bottleneck enzymes with negative dynamic sensitivities: ethanol
      fermentation systems as case studies.
AB  - Dynamic logarithmic gains (normalised time-varying sensitivities) or their
      products with metabolite concentrations, called an instantaneous bottleneck
      ranking indicator (instantaneous BR indicator), can express the time courses of
      bottleneck enzyme ranking. The integrated value of the instantaneous BR
      indicator, called an overall BR indicator, provides a ranking of bottleneck
      enzymes over the entire reaction period of time. Owing to the property of the
      logarithmic gains, these BR indicators are allowed to include both positive and
      negative values and in turn raise several questions on the identification of a
      bottleneck enzyme. To eliminate these questions, the present work studies the
      identification of bottleneck enzymes in four ethanol fermentation systems using
      suspended and immobilised cells at pH 4.5 and 5.5 as case studies. These systems
      consist of both intracellular reactions without cell growth (intracellular
      reaction systems) and those with cell growth (cell growth systems). The analyses
      of the intracellular reaction systems reveal that both the suspended and
      immobilised cell systems at pH 5.5 are not robust. In the cell growth systems,
      therefore, the analyses are conducted only for the suspended and immobilised cell
      models at pH 4.5. The enzyme glyceraldehyde 3-phosphate dehydrogenase (gapd)
      initially has the largest logarithmic gains under all conditions, whereas the
      system becomes insensitive to it over time. Interestingly, the instantaneous BR
      indicator for gapd is negatively large. Also, other indicators change in positive
      and/or negative regions. To deal with these values of different signs, all the
      indicators are integrated to obtain and rank the overall BR indicators in the
      order of the magnitudes of their absolute values. The result shows that the
      ranking of enzymes are completely identical to that of the final ethanol
      concentrations obtained by finitely increasing or decreasing the relevant enzyme
      activities in accordance with the signs of overall BR indicators. This result
      indicates that the enzymes must be ranked in the order of the magnitudes of their
      absolute values to determine a bottleneck enzyme. As a result, the analyses of
      the intracellular reaction systems reveal that the bottleneck enzyme is switched
      from a membrane-bound glucose transporter enzyme to phosphofructokinase when the
      cell-retaining condition is changed from suspension to immobilisation. In the
      cell growth systems, gapd is identified as the most likely bottleneck enzyme,
      suggesting that the gapd activity must be decreased to increase the ethanol
      productivity.

PMID- 20132845
TI  - A bicistronic lentiviral vector based on the 1D/2A sequence of foot-and-mouth
      disease virus expresses proteins stoichiometrically.
AB  - Classic IRES sequences are notorious for exerting biased expression in favor of
      upstream coding regions when placed into polycistronic vectors. Here, we report
      the development of a bicistronic lentiviral system based on the 1D/2A sequence
      from the foot-and-mouth disease virus that is able to maintain tightly balanced
      control of upstream and downstream protein expression for several days at a
      stoichiometry very closely approaching 1.0. Our results suggest that the 1D/2A
      sequence can be optimized in an FUGW lentiviral setting to coordinate expression
      of multiple polypeptides, presenting a potentially valuable tool to signaling
      network researchers and to the gene therapy community.

PMID- 20132846
TI  - Monooxygenases as biocatalysts: Classification, mechanistic aspects and
      biotechnological applications.
AB  - Monooxygenases are enzymes that catalyze the insertion of a single oxygen atom
      from O(2) into an organic substrate. In order to carry out this type of reaction,
      these enzymes need to activate molecular oxygen to overcome its spin-forbidden
      reaction with the organic substrate. In most cases, monooxygenases utilize
      (in)organic cofactors to transfer electrons to molecular oxygen for its
      activation. Monooxygenases typically are highly chemo-, regio-, and/or
      enantioselective, making them attractive biocatalysts. In this review, an
      exclusive overview of known monooxygenases is presented, based on the type of
      cofactor that these enzymes require. This includes not only the cytochrome P450
      and flavin-dependent monooxygenases, but also enzymes that utilize pterin, metal
      ions (copper or iron) or no cofactor at all. As most of these monooxygenases
      require nicotinamide coenzymes as electron donors, also an overview of current
      methods for coenzyme regeneration is given. This latter overview is of relevance
      for the biotechnological applications of these oxidative enzymes.

PMID- 20132847
TI  - Development of an autofluorescent Pseudomonas nitroreducens with
      dehydrochlorinase activity for efficient mineralization of gamma
      hexachlorocyclohexane (gamma-HCH).
AB  - Biodegradation or bioremediation is a more efficient and environmental friendly
      method for detoxification of hexachlorocyclohexane (HCH) residues compared to
      physical and chemical methods. Here, we report the functional expression of
      dehydrochlorinase (LinA) and enhanced green fluorescent protein (EGFP) in
      Pseudomonas nitroreducens for efficient biodegradation of gamma-HCH. The broad
      host-range plasmid pVAG33, harboring dehydrochlorinase gene (linA) and enhanced
      green fluorescent protein gene (egfp), was constructed and transformed into the
      soil-isolated 1,2,4-trichlorobenzene (1,2,4-TCB)-degrading strain P.
      nitroreducens J5-1. Functional expression of LinA and EGFP was confirmed in the
      recombinant strain by Western-blotting analysis and by determining their
      enzymatic activities and fluorescence intensity. The recombinant strain could
      rapidly degrade 10microg ml(-1) gamma-HCH in 28h determined by GC-ECD analysis.
      It could completely mineralize gamma-HCH via gamma-HCH through 1,2,4-TCB and
      3,4,6-trichlorocatechol and eventually entered the TCA cycle as determined by GC
      MS analysis. The engineered strain can be applied in the form of a biocatalyst in
      a bioreactor for rapid degradation of HCH and chlorobenzene residues. Meanwhile,
      it can be easily monitored on-line by fluorescence of EGFP for its activity and
      fate.

PMID- 20132848
TI  - Synthetic surfaces for human embryonic stem cell culture.
AB  - Human embryonic stem cells (hESCs) have numerous potential biomedical
      applications owing to their unique abilities for self-renewal and pluripotency.
      Successful clinical application of hESCs and derivatives necessitates the culture
      of these cells in a fully defined environment. We have developed a novel peptide
      based surface that uses a high-affinity cyclic RGD peptide for culture of hESCs
      under chemically defined conditions.

PMID- 20132849
TI  - The non-essential left end region of the fowl adenovirus 9 genome is suitable for
      foreign gene insertion/replacement.
AB  - The goals of this study were to demonstrate that a non-essential region at the
      left end of the fowl adenovirus 9 (FAdV-9) genome could be used to generate
      recombinant viruses, examine their in vitro growth characteristics and determine
      their ability to transduce non-avian cells. Three FAdV-9 vectors (rFAdV-9s) were
      generated carrying the enhanced-green fluorescent protein (EGFP) gene: FAdV
      9inEGFP, FAdV-9 Delta 1-EGFP and FAdV-9 Delta 4-EGFP. FAdV-9inEGFP carried the
      EGFP cassette inserted into the non-essential region without deletion resulting
      in an increase of the genome size to 103.7% of the wild-type. FAdV-9 Delta 1-EGFP
      and FAdV-9 Delta 4-EGFP (rFAdV-9 Delta s) carried the EGFP cassette replacing the
      non-essential sequences at nucleotides 1194-2342 and 491-2782, respectively. All
      rFAdV-9s had wild-type growth kinetics and plaque morphology. The rFAdV-9 Delta s
      replicated in CH-SAH cells with the same titers as the wild-type virus. The FAdV
      9inEGFP titers were approximately 1 log lower than those of rFAdV-9 Delta s and
      wt FAdV-9 at 36 and 48 h post-infection (h.p.i.). EGFP was expressed in avian and
      mammalian cells infected with rFAdV-9s. EGFP expression, based on
      spectrofluorometry, was significantly higher in chicken hepatoma cells infected
      with FAdV-9inEGFP than in those with rFAdV-9 Delta s at 18 and 24h.p.i,
      suggesting a functional role of some or all non-essential ORFs on foreign gene
      expression. This study demonstrated the suitability of the non-essential region
      as an insertion/replacement site for foreign genes to generate FAdV-9-based
      vectors that can be applied as recombinant vaccines for poultry or gene delivery
      vehicles for mammalian systems.

PMID- 20132850
TI  - Heterogeneity in spike protein genes of porcine epidemic diarrhea viruses
      isolated in Korea.
AB  - Porcine epidemic diarrhea virus (PEDV) has plagued the domestic swine industry in
      Korea causing significant economic impacts on pig production nationwide. In the
      present study, we determined the complete nucleotide sequences of the spike (S)
      glycoprotein genes of seven Korean PEDV isolates. The entire S genes of all
      isolates were found to be nine nucleotides longer in length than other PEDV
      reference strains. This size difference was due to the combined presence of
      notable 15 bp insertion and 6 bp deletion within the N-terminal region of the S1
      domain of the Korean isolates. In addition, the largest number of amino acid
      variations was accumulated in the S1 N-terminal region, leading to the presence
      of hypervariability in the isolates. Sequence comparisons at the peptide level of
      the S proteins revealed that all seven Korean isolates shared diverse
      similarities ranging from a 93.6% to 99.6% identity with each other but exhibited
      a 92.2% to 93.7% identity with other reference strains. Collectively, the
      sequence analysis data indicate the diversity of the PEDV isolates currently
      prevalent in Korea that represents a heterogeneous group. Phylogenetic analyses
      showed two separate clusters, in which all Korean field isolates were grouped
      together in the second cluster (group 2). The results indicate that prevailing
      isolates in Korea are phylogenetically more closely related to each other rather
      than other reference strains. Interestingly, the tree topology based on the
      nucleotide sequences representing the S1 domain or the S1 N-terminal region most
      nearly resembled the full S gene-based phylogenetic tree. Therefore, our data
      implicates a potential usefulness of the partial S protein gene including the N
      terminal region in unveiling genetic relatedness of PEDV isolates.

PMID- 20132851
TI  - Antigenic domains analysis of classical swine fever virus E2 glycoprotein by
      mutagenesis and conformation-dependent monoclonal antibodies.
AB  - Glycoprotein E2 of classical swine fever virus (CSFV) is the major antigenic
      protein exposed on the outer surface of the virion that induces main neutralizing
      antibodies during infection in pigs. This study displays the differences in
      antigenicity of E2 between vaccine and field strains of CSFV by their variable
      reaction patterns between expressed proteins and monoclonal antibodies (mAbs).
      The D/A domains of various CSFVs were relatively conserved and recognized by all
      mAbs against the A domain. However, mAbs against B/C domains were able to
      differentiate field viruses TD/96/TWN (subgroup 2.1) and 94.4/IL/94/TWN (subgroup
      3.4) from the vaccine virus LPC/AHRI (subgroup 1.1). By analysis of expressed
      truncated proteins, the epitope(s) on B/C domains were mapped to the N-terminal
      90 residues of E2 between amino acids 690 and 779. Site-directed mutagenesis
      further showed that residues (693)C, (737)C, (771)L, (772)L, (773)F and (774)D
      were critical for the reactivity of E2 protein with mAbs. Thus, the B/C domains
      are responsible for antigen specificity among various CSFVs, and the disulfide
      bond and motif (771)LLFD(774) are essential for the structural integrity of its
      conformational recognition. These data significantly increase our understanding
      of the antigenic structure of E2 for antibody binding.

PMID- 20132852
TI  - Human adrenomedullin and its binding protein ameliorate sepsis-induced organ
      injury and mortality in jaundiced rats.
AB  - Sepsis is a serious complication for patients with obstructive jaundice. Although
      administration of adrenomedullin (AM) in combination with its binding protein
      (AMBP-1) is protective after injury, it remains unknown whether AM/AMBP-1
      ameliorates sepsis-induced organ injury and mortality in the setting of biliary
      obstruction. The aim of this study is, therefore, to test the efficacy of human
      AM/AMBP-1 in a rat model of obstructive jaundice and polymicrobial sepsis. To
      study this, obstructive jaundice was induced in male adult rats (275-325g) by
      common bile duct ligation (BDL). One week after BDL, the rats were subjected to
      sepsis by cecal ligation and puncture (CLP). Plasma levels of AM and AMBP-1 were
      measured at 20h after CLP. In additional groups of BDL+CLP rats, human AM/AMBP-1
      (24/80microg/kg body weight (BW)) or vehicle (i.e., human albumin) was
      administered intravenously at 5h after CLP. Blood and tissue samples were
      collected at 20h after CLP for various measurements. To determine the long-term
      effect of human AM/AMBP-1 after BDL+CLP, the gangrenous cecum was removed at 20h
      after CLP and 7-day survival was recorded. Our results showed that plasma levels
      of AM were significantly increased while AMBP-1 levels were markedly decreased
      after BDL+CLP (n=8, P<0.05). Administration of human AM/AMBP-1 attenuated tissue
      injury and inflammatory responses after BDL+CLP. Moreover, human AM/AMBP-1
      significantly increased the survival rate from 21% (n=14) to 53% (n=15). Thus,
      human AM/AMBP-1 ameliorates sepsis-induced organ injury and mortality in
      jaundiced rats. Human AM/AMBP-1 can be further developed as a novel treatment for
      sepsis in jaundiced patients.

PMID- 20132853
TI  - Kappa-opioid receptor-mediated modulation of innate immune response by dynorphin
      in teleost Channa punctatus.
AB  - The immunomodulatory role of endogenous opioid peptides released during stress
      has been extensively studied in mammals, but least explored in lower vertebrates.
      The present in vitro study for the first time reports the specific opioid
      receptor-mediated immunomodulatory role of dynorphin-A((1-17)) in ectotherms.
      Dynorphin-A((1-17)) had pleiotropic effects on phagocyte functions, stimulatory
      on phagocytosis and superoxide production while inhibitory on the nitrite
      release. However, the effect of dynorphin-A((1-17)), whether stimulatory or
      inhibitory, markedly declined at high (10(-5)M) concentration. Dynorphin-A((1
      17)) seems to mediate its action through opioid receptors since non-selective
      opioid receptor antagonist, naltrexone, completely blocked the effect of
      dynorphin-A((1-17)) on phagocytosis, superoxide production and nitrite release.
      Moreover, among specific opioid receptors antagonists, only selective kappa
      (kappa)-opioid receptor antagonist norbinaltorphimine was capable to antagonize
      the pleiotropic effects on phagocyte functions. The present study provides the
      direct evidence of immunomodulatory role of dynorphin-A((1-17)) via kappa-opioid
      receptor in freshwater teleost Channa punctatus.

PMID- 20132854
TI  - Anti-tumor effects of a novel chimeric peptide on S180 and H22 xenografts bearing
      nude mice.
AB  - In recent years, many endogenous peptides have been identified by screening
      combinatory phage display peptide library, which play important roles in the
      process of angiogenesis. A heptapeptide, ATWLPPR, binds specifically to NRP-1 and
      selectively inhibits VEGF165 binding to VEGFR-2. Another heptapeptide, NLLMAAS,
      blocks both Ang-1 and Ang-2 binding to Tie-2 in a dose-dependent manner. In the
      present study, we aimed to connect ATWLPPR (V1) with NLLMAAS (V2) via a flexible
      linker, Ala-Ala, to reconstruct a novel peptide ATWLPPRAANLLMAAS (V3). We firstly
      investigated the anti-tumor and anti-angiogenic effects of peptide V3 on sarcoma
      S180 and hepatoma H22 bearing BALB/c nude mice. Mice were continuously
      subcutaneously administrated with normal saline, V1 (320microg/kg/d), V2
      (320microg/kg/d), V1+V2 (320microg/kg/d), and V3 (160, 320 and 480microg/kg/d),
      for 7 days. Treatment with peptide V3 could significantly reduce the tumor weight
      and volume. Pathological examination showed that the tumors treated with peptide
      V3 had a larger region of necrosis than that of peptide V1, V2, and V1+V2 at the
      same dose. A significant decrease of microvessel density (MVD) in a dose
      dependent manner was observed in each group of peptide V3. The results of
      pathological examination on normal tissue, lung, heart, liver, spleen, kidney and
      white blood cells showed that peptide V3 might have no significant toxicity. In
      conclusion, our results demonstrated that peptide V3 could be more effective on
      inhibiting tumor growth and angiogenesis than that of V1, V2, and V1+V2. Peptide
      V3 could be considered as a novel chimeric peptide with potent anti-tumor
      activity.

PMID- 20132855
TI  - Adrenomedullin in sinusoidal endothelial cells play protective roles against cold
      injury of liver.
AB  - Donor organ damage caused by cold preservation is a major problem affecting liver
      transplantation. Cold preservation most easily damages liver sinusoidal
      endothelial cells (LSECs), and information about the molecules modulating LSECs
      function can provide the basis for new therapeutic strategies. Adrenomedullin
      (AM) is a peptide known to possess anti-apoptotic and anti-inflammatory
      properties. AM is abundant in vascular endothelial cells, but levels are
      comparatively low in liver, and little is known about its function there. In this
      study, we demonstrated both AM and its receptors are expressed in LSECs. AM
      treatment reduced LSECs loss and apoptosis under cold treatment. AM also
      downregulated cold-induced expression of TNFalpha, IL1beta, IL6, ICAM1 and VCAM1.
      AM reduced apoptosis and expression of ICAM1 and VCAM1 in an in vivo liver model
      subjected to cold storage. Conversely, apoptosis was exacerbated in livers from
      AM and RAMP2 (AM receptor activity-modifying protein) knockout mice. These
      results suggest that AM expressed in LSECs exerts a protective effect against
      cold-organ damage through modulation of apoptosis and inflammation.

PMID- 20132856
TI  - Chemical composition, in vitro anti-microbial, antifungal and antioxidant
      activities of the essential oil and methanolic extract of Hymenocrater
      longiflorus Benth., of Iran.
AB  - In this study we identified the chemical composition, anti-microbial and
      antioxidant effects of essential oil and methanolic extract of Hymenocrater
      longiflorus Benth. Totally 87 volatile compounds from the essential oil in H.
      longiflorus, were identified by gas chromatography-mass spectrometry (GC-MS).
      These compounds are mainly monoterpene hydrocarbons, sesquiterpene hydrocarbons,
      oxygenated monoterpenes and oxygenated sesquiterpenoids compounds. The anti
      microbial and antifungal activity of plants extracts against several pathogenic
      microorganisms was studied by disc diffusion and minimum inhibitory concentration
      procedures. The results revealed that the essential oil and polar sub-fraction
      are effective mostly against Staphylococcus aureus, Aspergillus niger and Candida
      albicans. The antioxidant activity was also determined by 1,1'-diphenyl-2-picryl
      hydrazyl (DPPH) free radical scavenging, beta-carotene linoleic acid assay and
      reducing power. In addition the total phenol of essential oil (54.6+/-1.2), polar
      sub-fraction (50.0+/-1.4) and non-polar sub-fraction (64.7+/-2.0) were
      determined.

PMID- 20132857
TI  - Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy.
AB  - Doxorubicin (Adriamycin) is a potent and broad-spectrum antineoplastic agent, the
      clinical utility of which is restricted by a cumulative and progressive
      cardiomyopathy that develops with repeated dosing. Fundamental to the cardiac
      failure is an interference with mitochondrial respiration and inhibition of
      oxidative phosphorylation. Global gene expression arrays in cardiac tissue
      indicate that inhibition of mitochondrial oxidative phosphorylation by
      doxorubicin (DOX) is accompanied by a decreased expression of genes related to
      aerobic fatty acid oxidation and a corresponding increase in expression of genes
      involved in anaerobic glycolysis, possibly as an alternate source for ATP
      production. The aim of this investigation was to determine whether this is also
      manifest at the metabonomic level as a switch in metabolic flux in cardiac
      tissue, and whether this can be averted by co-administering the cardioprotective
      drug, dexrazoxane (DZR). (13)C-isotopomer analysis of isolated perfused hearts
      from male Sprague-Dawley rats receiving 6 weekly s.c. injections of 2mg/kg DOX
      demonstrated a shift from the preferential oxidation of fatty acids to enhanced
      oxidation of glucose and lactate plus pyruvate, indicative of a compensatory
      shift towards increased pyruvate dehydrogenase activity. Substrate-selective
      isotopomer analysis combined with western blots indicate an inhibition of long
      chain fatty acid oxidation and not MCAD activity or fatty acyl-carnitine
      transport. Co-administering DZR averted many treatment-related changes in cardiac
      substrate metabolism, consistent with DZR being an effective cardioprotective
      agent against DOX-induced cardiomyopathy. This switch in substrate metabolism
      resembles that described for other models of cardiac failure; accordingly, this
      change in metabolic flux may represent a general compensatory response of cardiac
      tissue to imbalances in bioenergetic demand and supply, and not a characteristic
      unique to DOX-induced cardiac failure itself.

PMID- 20132858
TI  - Mitochondrial energy metabolism impairment and liver dysfunction following
      chronic exposure to dichlorvos.
AB  - Although the effects of acute pesticide poisoning are well known but, hardly any
      data exists regarding the health effects after long-term low-level exposure.
      Major unresolved issues include the effect of moderate exposure in the absence of
      poisoning. The present study elucidates a possible mechanism by which chronic
      organophosphate exposure (dichlorvos 6 mg/kg b.wt., s.c. for 12 weeks) causes
      liver dysfunction. Mitochondria, a primary site of cellular energy generation and
      oxygen consumption represent a likely target for organophosphate poisoning.
      Therefore, the objective of the current study was planned with an aim to
      investigate the effect of chronic dichlorvos exposure on liver mitochondrial
      electron transport chain (ETC), mitochondrial calcium uptake and its implications
      on the induction of liver enzymes and liver dysfunction in rodent model. Our
      results indicated decreased mitochondrial electron transfer activities of
      cytochrome oxidase along with altered mitochondrial complexes I and II activity.
      This decrease in the activities of electron transport complexes in turn affected
      the ATP synthesis and ATP levels adversely in the mitochondria isolated from
      dichlorvos (DDVP) treated rat liver. Mitochondrial preparation from DDVP treated
      rat liver demonstrated significant increase in mitochondrial Ca(2+) uptake and
      increase ROS levels. The alterations in the mitochondrial calcium uptake,
      mitochondrial electron transfer enzyme activities and increase ROS levels in turn
      might have caused an increase in liver enzymes (ALT, AST and ALP). The electron
      micrographs of liver cells depicted morphological changes in mitochondria as well
      as nucleus following 12 weeks of exposure to DDVP. These studies provide an
      evidence of impaired mitochondrial bioenergetics which may lead to liver
      dysfunction after chronic exposure to dichlorvos.

PMID- 20132859
TI  - Dentine desensitization induced by prophylactic and air-polishing procedures: an
      in vitro dentine permeability and confocal microscopy study.
AB  - OBJECTIVES: The exposure of dentinal tubules causes fluid movement and dentinal
      hypersensitivity. This study aimed at evaluating the dentine permeability after
      prophylactic measures performed on exposed dentine after immersion in artificial
      saliva and citric acid challenge. Confocal microscopy was performed to evaluate
      the percentage of occluded tubules (OCT%) and the changes in dentine morphology.
      METHODS: Prophy-powders and pastes were tested in this study. An oxalic acid
      liner was used as a positive control. Dentine discs from human third molars were
      treated with each material and the dentine permeability was evaluated using a
      fluid filtration system working at 20cm H(2)O. Artificial saliva and citric acid
      were used for the determination of changes in dentine permeability. The
      percentage of tubule occlusion capability (OCT%) was evaluated using confocal
      microscopy. RESULTS: All the products used in this study were able to
      significantly reduce the dentine permeability of acid-etched specimens. The use
      of the bioactive glass and sodium bicarbonate showed the highest values in
      dentine permeability reduction. However, the air-polishing procedures performed
      with Sylc bioactive glass powder created a dentine surface resistant to citric
      acid attack. CONCLUSION: Bioactive glass is suitable for treatment of dentinal
      hypersensitivity by creating a dentine surface resistant to citric acid attack.

PMID- 20132860
TI  - Overview: Japanese encephalitis.
AB  - Japanese encephalitis (JE) is one of the most important endemic encephalitis in
      the world especially in Eastern and Southeastern Asia. JE affects over 50,000
      patients and results in 15,000 deaths annually. JE virus is a single stranded
      positive sense RNA virus belonging to family flaviviridae. JE virus is
      transmitted through a zoonotic cycle between mosquitoes, pigs and water birds.
      Humans are accidentally infected and are a dead end host because of low level and
      transient viremia. In the northern region, large epidemics occur during summers
      whereas in the southern region JE tends to be endemic: cases occur throughout the
      year with a peak in the rainy season. Occurrence of JE is more closely related to
      temperature than to humidity. JE is regarded as a disease of children in the
      endemic areas but in the newly invaded areas, it affects both the adults and
      children because of the absence of protective antibodies. For every patient of
      JE, there are large numbers of subclinical cases (25-1000). Symptomatic JEV
      infection manifests with nonspecific febrile illness, aseptic meningitis or
      encephalitis. Encephalitis manifests with altered sensorium, seizures and focal
      neurological deficit. Acute flaccid paralysis may occur due to anterior horn cell
      involvement. A wide variety of movement disorders especially transient
      Parkinsonian features and dystonia (limb, axial, orofacial) are reported in 20
      60% patients. JE mainly affects thalamus, corpus striatum, brainstem and spinal
      cord as revealed by MRI and on autopsy studies. Coinfection of JE and
      cysticercosis occurs because of the important role of pigs in the life cycle of
      both JEV and cysticercosis. Laboratory diagnosis of JE is by IgM capture ELISA,
      which has high sensitivity and specificity. In the absence of specific antiviral
      therapy, JE is managed by symptomatic and supportive therapies and preventive
      measures. Purified formalin inactivated mouse brain derived vaccine and live
      attenuated vaccine (SA 14-14-2) are available; the latter is reported to be safe,
      effective and cheap. The role of Chimeric recombinant attenuated JE vaccine is
      under investigation. Control of JE is related to the wider issues of hygiene,
      environment, education and economy.

PMID- 20132861
TI  - Emotions beyond the laboratory: theoretical fundaments, study design, and
      analytic strategies for advanced ambulatory assessment.
AB  - Questionnaire and interview assessment can provide reliable data on attitudes and
      self-perceptions on emotion, and experimental laboratory assessment can examine
      functional relations between stimuli and reactions under controlled conditions.
      On the other hand, ambulatory assessment is less constrained and provides
      naturalistic data on emotion in daily life, with the potential to (1) assure
      external validity of laboratory findings, (2) provide normative data on
      prevalence, quality and intensity of real-life emotion and associated processes,
      (3) characterize previously unidentified emotional phenomena, and (4) model real
      life stimuli for representative laboratory research design. Technological
      innovations now allow for detailed ambulatory study of emotion across domains of
      subjective experience, overt behavior and physiology. However, methodological
      challenges abound that may compromise attempts to characterize biobehavioral
      aspects of emotion in the real world. For example, emotional effects can be
      masked by social engagement, mental and physical workloads, as well as by food
      intake and circadian and quasi-random variation in metabolic activity. The
      complexity of data streams and multitude of factors that influence them require a
      high degree of context specification for meaningful data interpretation. We
      consider possible solutions to typical and often overlooked issues related to
      ambulatory emotion research, including aspects of study design decisions,
      recording devices and channels, electronic diary implementation, and data
      analysis.

PMID- 20132862
TI  - Picture representation during REM dreams: a redox molecular hypothesis.
AB  - A novel molecular hypothesis about visual perception and imagery has recently
      been proposed (Bokkon, 2009; BioSystems). Namely, external electromagnetic
      visible photons are converted into electrical signals in the retina and are then
      conveyed to V1. Next, these retinotopic electrical signals (spike-related
      electrical signals along classical axonal-dendritic pathways) can be converted
      into synchronized bioluminescent biophoton signals (inside the neurons) by
      neurocellular radical reactions (redox processes) in retinotopically organized V1
      mitochondrial cytochrome oxidase-rich visual areas. The bioluminescent photonic
      signals (inside the neurons) generated by neurocellular redox/radical reactions
      in synchronized V1 neurons make it possible to produce computational biophysical
      pictures during visual perception and imagery. Our hypothesis is in line with the
      functional roles of reactive oxygen and nitrogen species in living cells and
      states that this is not a random process, but rather a strict mechanism used in
      signaling pathways. Here, we suggest that intrinsic biophysical pictures can also
      emerge during REM dreams.

PMID- 20132863
TI  - 17 beta-estradiol activates rapid signaling pathways involved in rat pachytene
      spermatocytes apoptosis through GPR30 and ER alpha.
AB  - Aim of the present study was to investigate whether estrogens were able to
      directly activate rapid signaling pathways controlling spermatogenesis in rat
      pachytene spermatocytes (PS). Classically, estrogens act by binding to estrogen
      receptors (ERs) alpha and beta. Recently, it has been demonstrated that rapid
      estrogen action can also be activated through the G-protein-coupled receptor
      (GPR)-30. Herein, we demonstrated that rat PS express ER alpha, ER beta and
      GPR30. Treatment of PS with estradiol (E2), the selective GPR30 agonist G1 and
      the selective ER alpha agonist PPT determined activation of ERK1/2 which are part
      of GPR30 signaling cascade. ERK1/2 activation in response to E2 and G1 was
      correlated to an increased phosphorylation of c-Jun. All treatments failed to
      induce these responses in the presence of EGFR inhibitor AG1478, ERK inhibitor
      PD98059 and ER inhibitor ICI182780. mRNA expression of cell cycle regulators
      cyclin A1 and B1 was downregulated by E2 and G1 while an up-regulation of
      proapoptotic factor Bax was observed in the same conditions. These data
      demonstrate that E2, working through both ER alpha and/or GPR30, activates in PS
      the rapid EGFR/ERK/c-Jun pathway, modulating the expression of genes involved in
      the balance between cellular proliferation and apoptosis.

PMID- 20132864
TI  - Peripheral inhibition of glutaminase reduces carrageenan-induced Fos expression
      in the superficial dorsal horn of the rat.
AB  - In inflamed tissue, the levels of the excitatory amino acid glutamate are
      increased. Glutamate sensitizes peripheral axons of primary afferent neurons
      during inflammation leading to decreased firing threshold and hyperexcitability.
      One proposed source of glutamate is the primary afferent. Antagonizing glutamate
      receptors on peripheral axons of primary afferents during inflammation provides
      analgesia in animals and humans. The enzyme glutaminase is used by primary
      sensory neurons to convert glutamine to glutamate, and peripheral inhibition of
      glutaminase with 6-diazo-5-oxo-l-norleucine (DON) provides long-lasting analgesia
      during inflammation. In this study, we measured the effects of glutaminase
      inhibition on carrageenan-induced spinal Fos expression. Rats were given
      intraplantar injections of carrageenan and treated locally with either vehicle or
      DON. After 3h of inflammation, hind paw swelling and spinal expression of Fos
      were examined. CellProfiler was used to automate Fos nuclei counting in five
      laminar groupings in the spinal cord (I-II, III-IV, V-VI, VII-IX, X). Carrageenan
      increased hind paw thickness by approximately 70% and spinal Fos expression in
      superficial (I-II) and deep (V-VI) laminae by 10-fold and 5-fold, respectively.
      Treatment with DON reduced hind paw swelling by approximately 13% and suppressed
      Fos expression in the laminae I-II by approximately 54%, but not the deep
      laminae. Our results further support the notion of glutamate as a peripheral
      inflammatory mediator and indicate that glutaminase should be considered as a
      novel therapeutic target for treatment of inflammatory pain.

PMID- 20132865
TI  - Modulation of histamine H(3) receptor function by monovalent ions.
AB  - Monovalent ions differently affect ligand binding to G protein-coupled receptors
      (GPCRs) by as yet poorly defined mechanisms. In particular, NaCl often decreases
      the affinity of agonists but increases it for antagonists. We examined the effect
      of various monovalent ions on human histamine H(3) receptor (hH(3)R), co
      expressed with mammalian G proteins (Galpha(i1), Galpha(i2), Galpha(i3) or
      Galpha(o1), and beta(1)gamma(2) dimers, respectively) in Sf9 insect cell
      membranes, with respect to agonist binding and G protein activation. NaCl (100mM)
      had no effect on affinity of the agonist [(3)H]N(alpha)-methylhistamine
      ([(3)H]NAMH). In steady-state GTPase assays, the endogenous agonist histamine had
      a lower potency and the inverse agonist thioperamide had a higher potency, when
      NaCl (100mM) was present. Monovalent ions reduced H(3)R-regulated signalling in
      the order of efficacy Li(+) approximately Na(+) approximately K(+)<Cl(-)<Br(-)<I(
      ). NaCl had a stronger effect on basal hH3R-signalling when Galpha(i3) was co
      expressed. Asp80(2.50), a putative interaction site for Na(+), was mutated to
      Asn80(2.50) (D2.50N-hH(3)R). Strikingly, the mutation was unable to activate
      Galpha(i3) at all. The effects can be explained by a model, where (i) monovalent
      ions as well as a charge-neutralizing mutation of Asp80(2.50) generally reduce
      the interaction of hH(3)R with G proteins, (ii) monovalent anions increase the
      affinity of G proteins for GDP and thus, indirectly affect their interaction with
      hH(3)R and, (iii) Asp80(2.50) is a key residue for hH(3)R/Galpha(i3)-protein
      activation. The latter result suggests that hH(3)R/G protein-coupling interfaces
      may differ even between closely related subunits.

PMID- 20132866
TI  - Dorsal root ganglion neurons respond with prolonged extracellular signal
      regulated protein kinase phosphorylation following noxious heat and cold
      stimulation.
AB  - In the present study the time course of extracellular signal-regulated protein
      kinase phosphorylation (pERK1/2 appearance) in lumbar sensory dorsal root ganglia
      (DRG) was determined following a 5-min noxious heat or a noxious cold stimulus to
      the hind paw of the rat. The thermal stimuli were chosen to activate transient
      receptor potential (TRP) channels, but not to induce tissue damage. A
      quantitative analysis of phospho-ERK1/2 was performed by protein extraction and
      Western blot analysis. Western blot analysis showed that following the heat
      stimulus, phosphorylation of ERK1/2 increased 2-3-fold between 10 and 30min in
      the DRG on the ipsilateral side. High levels were maintained from 30min up to
      16h. Following the cold stimulus to the paw, pERK1/2 immediately increased 2-fold
      within 2min in the DRG on the ipsilateral side, it declined within 2h and reached
      a second peak at 4h. In the DRGs on the contralateral side of the paw's heat or
      cold immersion the pERK1/2 remained low at all time points investigated.
      Fluorescence immunohistochemistry of the DRG following the thermal stimuli
      revealed an increased cytoplasmic staining for pERK1/2 in neurons. The present
      results show that following a 5-min nociceptive thermal stimulus sensory neurons
      respond with a characteristic long-lasting phosphorylation of ERK1/2.

PMID- 20132867
TI  - Alterations in protein expression and membrane properties during Muller cell
      gliosis in a murine model of transient retinal ischemia.
AB  - Retinal Muller glial cells are involved in K+ ion homeostasis of the tissue.
      Inwardly rectifying K(+) (Kir) channels play a decisive role in the process of
      spatial K+ buffering. It has been demonstrated that Kir-mediated currents of
      Muller cells are downregulated in various cases of retinal neurodegeneration.
      However, this has not yet been verified for any murine animal model. The aim of
      the present study was to investigate Muller cells after transient retinal
      ischemia in mice. High intraocular pressure was applied for 1h; the retina was
      analysed 1 week later. We studied protein expression in the tissue by
      immunohistochemistry, and membrane currents of isolated cells by patch-clamp
      experiments. We found the typical indicators of reactive gliosis such as
      upregulation of glial fibrillary acidic protein. Moreover, the membrane
      capacitance of isolated Muller cells was increased and the amplitudes of Kir
      mediated currents were slightly, but significantly decreased. This murine high
      intraocular pressure model of transient retinal ischemia is proposed as a
      versatile tool for further studies on Muller cell functions in retinal
      degeneration.

PMID- 20132868
TI  - Type III intermediate filament peripherin inhibits neuritogenesis in type II
      spiral ganglion neurons in vitro.
AB  - Peripherin, a type III intermediate filament protein, forms part of the
      cytoskeleton in a subset of neurons, most of which have peripheral fibre
      projections. Studies suggest a role for peripherin in axon outgrowth and
      regeneration, but evidence for this in sensory and brain tissues is limited. The
      exclusive expression of peripherin in a sub-population of primary auditory
      neurons, the type II spiral ganglion neurons (SGN) prompted our investigation of
      the effect of peripherin gene deletion (pphKO) on these neurons. We used confocal
      immunofluorescence to examine the establishment of the innervation of the
      cochlear outer hair cells by the type II SGN neurites in vivo and in vitro, in
      wildtype (WT) and pphKO mice, in the first postnatal week. The distribution of
      the type II SGN nerve fibres was normal in pphKO cochleae. However, using P1
      spiral ganglion explants under culture conditions where the majority of neurites
      were derived from type II SGN, pphKO resulted in increased numbers of
      neurites/explant compared to WT controls. Type II SGN neurites from pphKO
      explants extended approximately double the distance of WT neurites, and had
      reduced complexity based on greater distance between turning points. Addition of
      brain-derived neurotrophic factor (BDNF) to the culture media increased neurite
      number in WT and KO explants approximately 30-fold, but did not affect neurite
      length or distance between turning. These results indicate that peripherin may
      interact with other cytoskeletal elements to regulate outgrowth of the peripheral
      neurites of type II SGN, distinguishing these neurons from the type I SGN
      innervating the inner hair cells.

PMID- 20132869
TI  - Mice overexpressing corticotropin-releasing factor show brain atrophy and motor
      dysfunctions.
AB  - Chronic stress and persistently high glucocorticoid levels can induce brain
      atrophy. Corticotropin-releasing factor (CRF)-overexpressing (OE) mice are a
      genetic model of chronic stress with elevated brain CRF and plasma corticosterone
      levels and Cushing's syndrome. The brain structural alterations in the CRF-OE
      mice, however, are not well known. We found that adult male and female CRF-OE
      mice had significantly lower whole brain and cerebellum weights than their wild
      type (WT) littermates (347.7+/-3.6mg vs. 460.1+/-4.3mg and 36.3+/-0.8mg vs.
      50.0+/-1.3mg, respectively) without sex-related difference. The
      epididymal/parametrial fat mass was significantly higher in CRF-OE mice. The
      brain weight was inversely correlated to epididymal/parametrial fat weight, but
      not to body weight. Computerized image analysis system in Nissl-stained brain
      sections of female mice showed that the anterior cingulate and sensorimotor
      cortexes of CRF-OE mice were significantly thinner, and the volumes of the
      hippocampus, hypothalamic paraventricular nucleus and amygdala were significantly
      reduced compared to WT, while the locus coeruleus showed a non-significant
      increase. Motor functions determined by beam crossing and gait analysis showed
      that CRF-OE mice took longer time and more steps to traverse a beam with more
      errors, and displayed reduced stride length compared to their WT littermates.
      These data show that CRF-OE mice display brain size reduction associated with
      alterations of motor coordination and an increase in visceral fat mass providing
      a novel animal model to study mechanisms involved in brain atrophy under
      conditions of sustained elevation of brain CRF and circulating glucocorticoid
      levels.

PMID- 20132870
TI  - Developmental and genetic influences on prefrontal function in adolescents: a
      longitudinal twin study of WCST performance.
AB  - Adolescence is characterized by a relative immaturity of the prefrontal cortex
      and associated cognitive control functions, which is hypothesized to be a major
      contributing factor to high-risk behaviors. However, little is known about the
      role of genetic and environmental factors in frontal brain development during
      adolescence. Here we examined heritability of performance on the Wisconsin Card
      Sorting Test (WCST), an established neuropsychological measure of prefrontally
      mediated executive functioning, in a longitudinal sample of adolescent twins
      (n=747) tested at ages 12 and 14. WSCT performance significant improved with age
      as indicated by a decrease in the number of perseverative errors (p<0.001), which
      was paralleled by an increase in heritability in females (19% at age 12 and 49%
      at age 14) and shared environmental influences in males (non-significant at age
      12 and 34% at age 14). The results suggest increasing influence of familial
      factors on frontal executive functioning during adolescence, as well as gender
      differences in the relative role of genetic and environmental factors.

PMID- 20132871
TI  - The timing of impulse activity shapes the process of synaptic competition at the
      neuromuscular junction.
AB  - The development of neuromuscular junctions exhibits profound remodeling that
      brings from an immature state characterized by multiple motoneuronal inputs per
      muscle fiber, to a mature mononeuronal innervation. This striking elimination
      process occurs both perinatally and during adult reinnervation, and is also
      widely present in the developing CNS. The accelerating influence of the amount of
      impulse activity on this process, has been shown by various studies, but a more
      subtle role of the time correlation of action potential firing in the competing
      inputs, has also been suggested. Here we explore the latter influence using a rat
      adult model of neuromuscular junction formation, that is reinnervation following
      a motor nerve crush. This shares all important features with perinatal
      development, especially the strict juxtaposition of the competing inputs. In fact
      the regenerating axons converge on a single cluster of postsynaptic receptors,
      that is the original endplate of each muscle fiber. This focus on the spatial
      aspect of competition between nerve endings was missing in our previous
      experiments employing a similar paradigm. We impose a chronic synchronous firing
      to the competing terminals, by in vivo electrical stimulation of their axons
      distal to a sciatic nerve conduction block. Control preparations, with similar
      post-crush reinnervation, are left with their natural impulse activity
      unperturbed. We find that the experimental muscles display a prolonged duration
      of polyneuronal innervation with respect to controls, indicating that hebbian
      mechanisms participate in the synapse elimination process. Another aspect dealt
      with in our study is the genuine nature of the polyneuronal innervation occurring
      during adult muscle reinnervation, because it is supported by both confocal
      microscopy and by appropriate electrophysiological tests that exclude electrical
      coupling of myofibers by gap junctions.

PMID- 20132872
TI  - Differential role of GABAA and GABAB receptors in two distinct output stations of
      the rat striatum: studies on the substantia nigra pars reticulata and the globus
      pallidus.
AB  - The role of GABA(A) and GABA(B) receptors in the substantia nigra pars reticulata
      and the globus pallidus in turning behaviour of rats was studied. Unilateral
      injection of the GABA(A) receptor agonist muscimol (25 and 50 ng) into the
      substantia nigra pars reticulata elicited contralateral pivoting, namely tight
      head-to-tail turning marked by abnormal hindlimb backward stepping. This effect
      was GABA(A) receptor specific, since it was dose-dependent and prevented by co
      administration of the GABA(A) receptor antagonist bicuculline (100 and 200 ng)
      which alone did not elicit turning behaviour. Unilateral injection of the GABA(B)
      receptor agonist baclofen (100 and 200 ng) into the substantia nigra pars
      reticulata also produced contralateral pivoting. This effect was GABA(B) receptor
      specific, since it was dose-dependent and inhibited by the GABA(B) receptor
      antagonist CGP 55845 (200 ng) which alone did not elicit turning behaviour. In
      contrast, unilateral injection of bicuculline (100 and 200 ng) into the globus
      pallidus produced contralateral circling, namely turning marked by normal
      stepping. This effect was GABA(A) receptor specific, since it was dose-dependent
      and prevented by muscimol (50 ng), which alone did not elicit turning behaviour.
      Unilateral injection of baclofen (100 and 200 ng) into the globus pallidus dose
      dependently produced ipsilateral pivoting; this effect was inhibited by CGP 55845
      (200 ng), which alone did not elicit turning behaviour. The present study
      demonstrates that GABA(A) and GABA(B) receptors in the globus pallidus and the
      substantina nigra pars reticulata play differential roles in the production of
      turning behaviour. This study underlines the notion that the two types of
      turning, namely pivoting and circling, are valid tools to map out the information
      flow across the basal ganglia.

PMID- 20132873
TI  - Increased brain edema in aqp4-null mice in an experimental model of subarachnoid
      hemorrhage.
AB  - We investigated the role of the glial water channel protein aquaporin-4 in brain
      edema in a mouse model of subarachnoid hemorrhage in which 30 microl of blood was
      injected into the basal cisterns. Brain water content, intracranial pressure and
      neurological score were compared in wildtype and aquaporin-4 null mice. We also
      measured blood-brain barrier permeability, and the osmotic permeability of the
      glia limitans, one of the routes of edema elimination. Wildtype and aquaporin-4
      null mice had comparable baseline brain water content, intracranial pressure and
      neurological score. At 6 h after blood injection, aquaporin-4 null mice developed
      more brain swelling than wildtype mice. Brain water content increased by 1.5+/
      0.1% vs. 0.5+/-0.2% (Mean+/-Standard Error, P<0.0005) and intracranial pressure
      by 36+/-5 vs. 21+/-3 mm Hg (P<0.05) above pre-injection baseline, and
      neurological score was worse at 18.0 vs. 24.5 (median, P<0.05), respectively.
      Although subarachnoid hemorrhage produced comparable increases in blood-brain
      barrier permeability in wildtype and aquaporin-4 null mice, aquaporin-4 null mice
      had a twofold reduction in glia limitans osmotic permeability. We conclude that
      aquaporin-4 null mice manifest increased brain edema following subarachnoid
      hemorrhage as a consequence of reduced elimination of excess brain water.

PMID- 20132874
TI  - Proton pump inhibitor administration via nasogastric tube in pediatric practice:
      comparative analysis with protocol optimization.
AB  - Proton pump inhibitors (PPIs) are largely prescribed to children because their
      efficacy and tolerance are now well-established. One disadvantage resides in the
      absence of liquid form which causes problems for their administration in
      nasogastric tubes. Indeed, the absence of use recommendations involves many
      misuses responsible for inefficiency and/or tube obstruction. We tried to
      evaluate if PPIs can be administered through pediatric nasogastric tubes. We
      administered four PPIs (Omeprazole, esomeprazole, lansoprazole and lansoprazole
      orally disintegrating tablet) through nasogastric tubes. For each PPI a study
      plan was drawn up to assess the influence of different variables: the volume of
      water to dissolve or put in suspension the PPIs (2ml or 5ml), the volume of tube
      flush-through water post-PPI administration (2ml, 5ml or 10ml), the length (50cm
      or 125cm) and the diameter (6 or 8 French) of the polyurethane tubes. For each
      assay an analysis of each active ingredient at the tube outlet by UV spectrometry
      was carried out. All 6 F tubes were obstructed by PPIs. Through 8 F tubes, we
      observed a mean recovery of active ingredient of 86.2% for lansoprazole orally
      disintegrating tablet, 36.9% for esomeprazole but only 7.1% for lansoprazole and
      3.9% for omeprazole. It is disadvised using omeprazole and lansoprazole through 8
      F nasogastric tubes because no condition ensures the transit of an efficient
      concentration of active ingredient. For esomeprazole, the best conditions of
      administration were a water volume of 5ml and a rinse volume of 5ml but only a
      half of the microgranules administered were recovered. The most satisfactory
      results were obtained with lansoprazole orally disintegrating tablet. A 5ml
      volume of water diluent for suspension and a 10ml volume of flush-through water
      made it possible to deliver the full lansoprazole dose administered.

PMID- 20132875
TI  - Characterization and stability of solid dispersions based on PEG/polymer blends.
AB  - Solid dispersions were prepared by a melting method from the water-insoluble
      model drugs carbamazepine and nifedipine and polyethylene glycol 1500 (PEG 1500)
      or 1:1 mixtures of PEG 1500 and the polymers polyvinylpyrrolidone (PVP 30, PVP
      12), polyvinylpyrrolidone-co-vinylacetate (PVPVA) and Eudragit EPO (Eudragit) in
      order to combine advantages of the different carrier polymers (recrystallization
      inhibition, processability and stability). The solid dispersions were
      characterized by dissolution, powder X-ray diffractometry and microscopy directly
      after preparation and after storage for 3 and 6 months at 25 degrees C/0%
      relative humidity (RH) or 3 months at 40 degrees C/75% RH. More than 80% drugs
      were released from all solid dispersions within 20min. The dissolution rate of
      carbamazepine decreased in the order of PEG 1500>PEG 1500/Eudragit>PEG 1500/PVP
      30>PEG 1500/PVPVA>PEG 1500/PVP 12. The dissolution rank order was not directly
      correlated to the amorphous/crystalline state of the drugs, but rather to the
      properties of the PEG 1500/polymer compositions. Nifedipine was released in the
      order of PEG 1500>PEG 1500/PVPVA>PEG 1500/PVP 30>PEG 1500/PVP 12>PEG
      1500/Eudragit. Amorphous nifedipine was present in all PEG 1500/polymer
      dispersions except in pure PEG 1500 solid dispersion. The significant increase in
      dissolution rate of PEG 1500 solid dispersions was due to the reduced
      crystallinity of the drug and the excellent solubilisation properties of PEG
      1500. After 6 months storage at 25 degrees C/0% RH, the solid dispersions
      released both drugs in the order PEG 1500/PVPVA>PEG 1500/PVP 30>PEG 1500/PVP
      12>PEG 1500/Eudragit>PEG 1500. The stabilized amorphous state of the drug
      resulted in stable dissolution profiles of PEG 1500/PVPVA, PEG 1500/PVP 30 and
      PEG 1500/PVP 12 when compared to the PEG 1500 solid dispersions, which contained
      a higher amount of crystalline drug. The solid dispersions with PEG 1500/PVPVA or
      PEG 1500/PVP stored for 3 months at 40 degrees C/75% RH showed phase separation
      due to the hygroscopic properties of the polymers. The influence of 10% (w/w) of
      the solubilisers polyoxyl 40 hydrogenated castor oil (Cremophor), macrogol-15
      hydroxystearate (Solutol) and fatty alcohol alkoxylate (Pluronic) on the
      dissolution rate and the physical state of the drug was significant.

PMID- 20132876
TI  - Wound healing potential of Sambucus ebulus L. leaves and isolation of an active
      component, quercetin 3-O-glucoside.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Sambucus ebulus L. are used in
      Turkish folk medicine for treatment of high fever, rheumatic pains, snake bites
      and wounds. AIM OF THE STUDY: Four different solvent extracts by using n-hexane,
      diethyl ether, ethyl acetate and methanol were prepared from the leaves of
      Sambucus ebulus in order to investigate the claimed wound healing activity in
      vivo and isolation of active component(s) from the active extract through the
      bioassay-guided fractionation procedures. MATERIALS AND METHODS: Linear incision
      and circular excision wound models on rats and mice were employed. The methanol
      extract was fractionated by successive chromatographic techniques. Wound healing
      activity of each fraction was investigated following the bioassay-guided
      fractionation procedures. Moreover, the tissue samples were examined
      histopathologically. RESULTS: Significant wound healing activity was observed for
      the ointment prepared with methanol extract at 1% concentration. The methanol
      extract treated groups of animals showed 84.3% contraction in circular excision
      model, which was close to contraction value of the reference drug Madecassol
      (100%). On the other hand, a significant increase (43.7%) in the wound tensile
      strength was determined with the same extract on incision wound model.
      Subfractions showed significant but reduced wound healing activity on both in
      vivo wound models. A flavonoid derivative "quercetin 3-O-glucoside" was isolated
      and determined as one of the active component of active final subfraction. The
      results of histopathological examination supported the outcome of linear incision
      and circular excision wound models. CONCLUSION: The experimental data revealed
      that the methanolic extract of Sambucus ebulus leaves displayed remarkable wound
      healing activity.

PMID- 20132877
TI  - Metabolic activation capacity by primary hepatocytes expands the applicability of
      the embryonic stem cell test as alternative to experimental animal testing.
AB  - The murine embryonic stem cell test (EST) represents a validated alternative
      method for in vivo embryotoxicity testing. In the present study, primary
      hepatocytes were combined with the EST by a preincubation approach to improve its
      predictivity on bioactivation caused teratogenicity. As substances the well-known
      proteratogens cyclophosphamide (CPA) and valpromide (VPD) were used. The
      embryotoxic potential of CPA was detected by a strong decrease of the resulting
      ID(50)-concentration (50% inhibition of ES cell differentiation) after incubation
      with murine hepatocytes. Interspecies variation in metabolism was detected by
      testing VPD. After incubation of VPD with murine hepatocytes no inhibition of ES
      cell differentiation was observed, since hardly any teratogenic VPD metabolites
      were formed. In contrast, with human hepatocytes a significant conversion of VPD
      into the teratogen valproic acid (VPA) was observed. In summary we developed a co
      culture approach for embryotoxicity testing, whereby the test compounds were
      incubated with hepatocytes and the supernatant was added to the ES cell culture
      to obtain a dose dependency of the preincubated test substances.

PMID- 20132878
TI  - Health outcomes of children born to cosmetologists compared to children of women
      in other occupations.
AB  - The purpose of the study was to examine the health of children born to
      cosmetologists compared to the health of children of women working in other
      occupations. Cross-sectional data were analyzed from 319 cosmetologists and 366
      women in other occupations aged 21 to 55 years who reported at least one live
      birth. Repeated-measures modeling was used to account for lack of independence
      among multiple pregnancies per participant. The results showed that cosmetologist
      occupation was associated with having a child with a learning disorder; however,
      the strength of this association was attenuated and the odds ratio was not
      statistically significant after confounder adjustment. Cosmetologist occupation
      was not associated with other adverse health outcomes among the children born to
      women in such an occupation, including urinary/kidney health problems. The
      findings indicate that cosmetologists are not at increased risk of having a child
      with medical problems compared to women in other occupations.

PMID- 20132879
TI  - Reversible fetal renal failure after maternal treatment with Candesartan: a case
      report.
AB  - Despite data suggesting that angiotensin-receptor blockers (ARBs) are associated
      with increased risk to the fetus, there has been an increasing exposure of ARBs
      in pregnancy. We report a case report regarding a woman, who accidentally was
      treated with Candesartan during the first 22 weeks of pregnancy. At 22 weeks of
      gestation the fetal kidneys were oedematous with very little amniotic fluid. The
      prognosis for the fetus was considered poor. Five weeks after discontinuation of
      Candesartan normal quantities of amnionic fluid and a visible fetal bladder was
      registered. After delivery at week 31, creatinine clearance, diuresis and urine
      examination of the neonate were within normal limits. Ultrasound examinations of
      the kidneys showed bilaterally marked calices, small cysts and parenchymal
      increased echogenety at 1 week with complete sonographic normalization at 6
      weeks. However, experimental studies raise the question of potential long-term
      adverse effects, including renal dysfunction and arterial hypertension in
      adulthood.

PMID- 20132880
TI  - Potential estrogenic effect(s) of parabens at the prepubertal stage of a
      postnatal female rat model.
AB  - In this study, a female pubertal assay on the effects of parabens, including
      methyl-, ethyl-, propyl-, isopropyl-, butyl-, and isobutylparaben, was performed
      in a female Sprague-Dawley rat model during the juvenile-peripubertal period. The
      rats were orally treated with these parabens from postnatal day 21-40 in a dose
      dependent manner (62.5, 250 and 1000 mg/kg body weight [BW]/day). 17alpha
      Ethinylestradiol (1mg/kg BW/day) was used as a positive control and corn oil as a
      vehicle. A high dose of methyl- and isopropylparaben (1000 mg/kg BW/day) resulted
      in a significant delay in the date of vaginal opening and a decrease in length of
      the estrous cycle. In measurements of organ weight and body weight, we observed
      significant weight changes in ovaries, adrenal glands, thyroid glands, liver, and
      kidneys; conversely, body weight was not altered following paraben treatment. The
      potential effects of parabens on estrogenicity were shown in histopathological
      abnormities in the reproductive organs. Histological analysis of the ovaries from
      the peripubertal rats revealed a decrease of corpora lutea, increase in the
      number of cystic follicles, and thinning of the follicular epithelium. In
      addition, morphological studies of the uterus revealed the myometrial hypertrophy
      by a high dose of propyl- and isopropylparaben (1000 mg/kg-day), and in all dose
      groups of butyl- and isobutylparabens. However, no significant histopathological
      changes were observed in the other organs (i.e. adrenal and thyroid glands). We
      also observed a significant decrease in serum estradiol and thyroxine
      concentrations in methyl-, ethyl-, propyl-, isopropyl-, and isobutylparaben
      treated groups. A receptor-binding assay indicated that the relative binding
      affinities of parabens to estrogen receptors occurred in the order:
      isobutylparaben>butylparaben>isopropylparaben=propylparaben>ethylparaben. These
      values were much lower than the binding affinity for 17beta-estradiol. Taken
      together, long-term exposure to parabens, which show less estrogenic activity
      than estradiol, can produce suppressive effects on hormonal responsiveness and
      can disrupt the morphology of reproductive target tissues. In addition, the
      relation between thyroid weight and thyroid hormone may influence circulating
      levels of parabens, suggesting the effects of parabens as thyrotoxic during this
      critical stage of development in female rats.

PMID- 20132881
TI  - Prenatal developmental toxicity of gavage or feeding doses of 2-sec-butyl-4,6
      dinitrophenol in rats.
AB  - This study evaluated the prenatal developmental toxicity of the pesticide 2-sec
      butyl-4,6-dinitrophenol (dinoseb). Pregnant rats were given dinoseb by gavage at
      0, 8.0 or 10 mg/kg bw/day on days 6-15 of gestation, or in the diet at 0, 120 or
      200 ppm (0, 6.52 or 8.50 mg/kg bw/day) on days 6-16 of gestation, and litters
      were evaluated on day 20 of gestation. Maternal toxicity was observed as
      evidenced by significantly decreased body weight gain and reduced food
      consumption during the administration period in all the dinoseb-treated groups,
      and two dams died at 10 mg/kg bw/day. Significantly lower fetal weights and
      delayed skeletal ossification was observed in the dinoseb-treated groups except
      for the group fed dinoseb at 120 ppm. The teratogenic potential of the gavage
      dose of dinoseb was confirmed as evidenced by increased incidences of fetuses
      with external and skeletal malformations at 10 mg/kg bw/day. The incidence of
      fetuses with microphthalmia was significantly increased at this dose. On the
      other hand, feeding doses of dinoseb up to 200 ppm did not induce teratogenicity
      in this study. These data indicate that dinoseb is teratogenic at maternally
      toxic doses, but the exposure range of dinoseb at which malformations occur seems
      to be narrow.

PMID- 20132882
TI  - Redox-mediated reciprocal regulation of SERCA and Na+-Ca2+ exchanger contributes
      to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes.
AB  - Myocardial failure is associated with increased oxidative stress and abnormal
      excitation-contraction coupling characterized by depletion of sarcoplasmic
      reticulum (SR) Ca(2+) stores and a reduction in Ca(2+)-transient amplitude.
      Little is known about the mechanisms whereby oxidative stress affects Ca(2+)
      handling and contractile function; however, reactive thiols may be involved. We
      used an in vitro cardiomyocyte system to test the hypothesis that short-term
      oxidative stress induces SR Ca(2+) depletion via redox-mediated regulation of
      sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA) and the sodium-Ca(2+) exchanger
      (NCX) and that this is associated with thiol oxidation. Adult rat ventricular
      myocytes paced at 5 Hz were superfused with H(2)O(2) (100 microM, 15 min).
      H(2)O(2) caused a progressive decrease in cell shortening followed by diastolic
      arrest, which was associated with decreases in SR Ca(2+) content, systolic
      [Ca(2+)](i), and Ca(2+)-transient amplitude, but no change in diastolic
      [Ca(2+)](i). H(2)O(2) caused reciprocal effects on the activities of SERCA
      (decreased) and NCX (increased). Pretreatment with the NCX inhibitor KB-R7943
      before H(2)O(2) increased diastolic [Ca(2+)](i) and mimicked the effect of SERCA
      inhibition with thapsigargin. These functional effects were associated with
      oxidative modification of thiols on both SERCA and NCX. In conclusion, redox
      mediated SR Ca(2+) depletion involves reciprocal regulation of SERCA and NCX,
      possibly via direct oxidative modification of both proteins.

PMID- 20132883
TI  - Influence of serum albumin and the flavonol quercetin on the peroxidase activity
      of metmyoglobin.
AB  - Metmyoglobin (MbFe(III)), a major form of dietary iron, is an efficient inducer
      of lipid and protein oxidation. Indeed, MbFe(III) is able to cleave hydrogen
      peroxide and lipid hydroperoxides with subsequent formation of ferrylmyoglobin
      (MbFe(IV)=O) and lipid oxyl and peroxyl radicals. In the first part of this work,
      the mechanism of the reaction between MbFe(III) and H(2)O(2) is revisited with an
      emphasis on the influence of bovine serum albumin (BSA). BSA does not affect the
      rate of MbFe(IV)=O formation but inhibits the formation of a redox-inactive green
      pigment (heme-protein cross-link species). Although tightly bound to BSA, the
      flavonol quercetin is still able to reduce MbFe(IV)=O as a likely result of long
      range electron transfers within a protein-protein complex. In the second part,
      BSA is shown to strongly slow down the metmyoglobin-catalyzed consumption of
      linoleic acid hydroperoxides with formation of ketones as the main products. In
      the process, only low concentrations of ferrylmyoglobin are slowly accumulated. A
      catalytic mechanism is proposed that involves a one-electron-oxidized
      metmyoglobin species distinct from ferrylmyoglobin.

PMID- 20132884
TI  - A novel mifepristone-loaded implant for long-term treatment of endometriosis: in
      vitro and in vivo studies.
AB  - The objective of this study was to prepare a novel mifepristone-loaded
      PCL/Pluronic F68 implant to achieve long-term treatment of endometriosis.
      PCL/Pluronic F68 compound (90/10, w/w) with viscosity average molecular weight of
      65,000 was successfully synthesized. The end-capped Pluronic F68 was incorporated
      in PCL matrixes as molecular dispersion without forming a copolymer. The
      mifepristone-loaded implant made of PCL/Pluronic F68 compound was a cylindrical
      capsule with an outer diameter of 2.5mm and an inner diameter of 2.2mm. The
      surface of PCL/Pluronic F68 compound appears porous because Pluronic F68 which is
      water soluble could leach out due to the water phase. Drug loading of 0.75-, 1.5-
      and 3.0-cm length implants was 3.05+/-0.18, 6.06+/-0.41 and 11.87+/-0.39mg,
      respectively. A sustained mifepristone release rate without obvious initial burst
      and later decline over a period of 180d was observed. The cumulative drug release
      showed a linear relationship with time, indicating that mifepristone release from
      the implants followed zero-order kinetics (R(2)>0.99). The data showed that the
      C(max) and AUC(0-inf) were proportional to imlant length and dose, and all groups
      reached plasma C(max) at about the same time (approximately 7d) and had similar
      T(1/2) (approximately 150d) and MRT (approximately 220d). There were obvious
      inhibitory effects on the growth of endometrial explants in Wister rats in a dose
      dependent manner after administration of mifepristone-loaded implants with
      implant length from 1.5 to 9.0cm for 1-3 months. However, mifepristone-loaded
      implants with implant length of 12.0cm had no better inhibitory effects on the
      growth of endometrium when compared with the implants with implant length of
      9.0cm (P>0.05). In conclusion, subcutaneous implantation of mifepristone-loaded
      PCL/Pluronic F68 capsules was proven an effective means for long-term treatment
      of chronic endometriosis.

PMID- 20132885
TI  - Estranediols profiling in calves' urine after 17beta-nandrolone laureate ester
      administration.
AB  - 17beta-Nandrolone (17beta-NT) is one of the most recurrent forbidden anabolic
      steroid used in meat producing animals breeding. Because efficient control must
      both take into account metabolic patterns and associated kinetics of elimination,
      the metabolism of 17beta-NT in bovines has already been investigated and is well
      documented, but only focussing on its main metabolites (i.e. 17alpha-nandrolone,
      19-noretiocholanolone and 19-norandrostenedione). The goal of the present study
      was to enlarge this panel of 17beta-NT metabolites, especially through the
      urinary estranediols fraction in order to perform a more global steroid profiling
      upon 17beta-nortestosterone laureate ester administration in calves. A GC-MS/MS
      method has been developed to monitor and quantify 5 estranediols isomers
      including 5alpha-estrane-3beta,17beta-diol (abb), 5beta-estrane-3alpha,17beta
      diol (bab), 5alpha-estrane-3beta,17alpha-diol (aba), 5alpha-estrane-3alpha,17beta
      diol (aab) and 5beta-estrane-3alpha,17alpha-diol (baa). Their urinary elimination
      kinetics have been established allowing detection of 4 estranediols up to several
      days after administration. All animals demonstrated homogeneous patterns of
      elimination both from a qualitative (metabolite profile) and quantitative point
      of view (elimination kinetics in urine). 5alpha-Estrane-3beta,17alpha-diol (aba)
      was found as the major metabolite with concentrations up to 100microgL(-1).

PMID- 20132886
TI  - CD-ring modified vitamin D3 analogs and their superagonistic action.
AB  - Non-steroidal analogs of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] represent a most
      particular class of analogs because they are either not directly derived from the
      core 1,25(OH)2D3-structure or they have modifications in the core structure that
      are so drastic that the steroidal structure is lost. Non-steroidal CD-ring
      analogs of 1,25(OH)2D3 have been developed to study the role of the central rigid
      CD-ring system in the biological activity of 1,25(OH)2D3. Here we review the
      different classes of CD-ring analogs and highlight some representative analogs
      such as the fluorinated D-ring analogs CD578, WU515 and WY1113 which show
      markedly increased differentiating activity on human SW480-ADH colon cancer
      cells, characterized by a stronger induction of the invasion suppressor E
      cadherin and a stronger repression of the beta-catenin/TCF target oncogene c-Myc.
      Correspondingly, CD578, WU515 and WY1113 are more potent inhibitors of beta
      catenin/TCF signaling than 1,25(OH)2D3 and induce stronger VDR-coactivator
      interactions. Underlying the increased biological potency of analog CD578 are
      additional contacts between the side chain fluorine atoms of the analog with
      specific residues of helix 12 (H12) of the Vitamin D Receptor (VDR) and
      subsequent stronger VDR-coactivator interactions.

PMID- 20132887
TI  - NF-kappaB inhibition after neonatal cerebral hypoxia-ischemia improves long-term
      motor and cognitive outcome in rats.
AB  - We recently demonstrated that inhibition of the NF-kappaB-pathway by the specific
      peptide inhibitor TAT-NBD markedly reduced cerebral injury in a rat model of
      perinatal hypoxic-ischemic (HI) brain damage. The aim of the current study was to
      assess whether neuroprotection by TAT-NBD is associated with long-term functional
      improvements after neonatal HI. Postnatal-day 7 rats subjected to HI showed motor
      deficits in the cylinder rearing test and adhesive removal task. HI-treated
      animals also showed cognitive impairments in a visuo-spatial learning task
      (modified hole board) as defined by an increased latency to complete this task
      and increased numbers of short- and long-term memory errors. HI animals treated
      with TAT-NBD [20mg/kg i.p.] at 0 and 3h post-HI did not show impairments in the
      cylinder rearing test, adhesive removal task and modified hole board. In
      conclusion, the almost complete reduction in lesion size observed after TAT-NBD
      treatment was associated with long-lasting normalization of sensorimotor and
      cognitive functions.

PMID- 20132889
TI  - A matrix approach to tomographic reconstruction and its implementation on GPUs.
AB  - Electron tomography allows elucidation of the molecular architecture of complex
      biological specimens. Weighted backprojection (WBP) is the standard
      reconstruction method in the field. In this work, three-dimensional
      reconstruction with WBP is addressed from a matrix perspective by formulating the
      problem as a set of sparse matrix-vector products, with the matrix being constant
      and shared by all the products. This matrix approach allows efficient
      implementations of reconstruction algorithms. Although WBP is computationally
      simple, the resolution requirements may turn the tomographic reconstruction into
      a computationally intensive problem. Parallel systems have traditionally been
      used to cope with such demands. Recently, graphics processor units (GPUs) have
      emerged as powerful platforms for scientific computing and they are getting
      increasing interest. In combination with GPU computing, the matrix approach for
      WBP exhibits a significant acceleration factor compared to the standard
      implementation.

PMID- 20132888
TI  - Taurine deficiency damages photoreceptors and retinal ganglion cells in
      vigabatrin-treated neonatal rats.
AB  - The anti-epileptic drug vigabatrin induces an irreversible constriction of the
      visual field, but is still widely used to treat infantile spasms and some forms
      of epilepsy. We recently reported that vigabatrin-induced cone damage is due to a
      taurine deficiency. However, optic atrophy and thus retinal ganglion cell
      degeneration was also reported in children treated for infantile spasms. We here
      show in neonatal rats treated from postnatal days 4 to 29 that the vigabatrin
      treatment triggers not only cone photoreceptor damage, disorganisation of the
      photoreceptor layer and gliosis but also retinal ganglion cell loss. Furthermore,
      we demonstrate in these neonatal rats that taurine supplementation partially
      prevents these retinal lesions and in particular the retinal ganglion cell loss.
      These results provide the first evidence of retinal ganglion cell neuroprotection
      by taurine. They further confirm that taurine supplementation should be
      administered with the vigabatrin treatment for infantile spasms or epilepsy.

PMID- 20132890
TI  - Three-dimensional reconstruction of collagen-proteoglycan interactions in the
      mouse corneal stroma by electron tomography.
AB  - Corneal transparency is fundamental to the visual system, and is directly related
      to the ordered collagen fibril architecture that the cornea maintains.
      Proteoglycans, through their protein core and highly anionic glycosaminoglycan
      side chains, are thought to regulate the collagen organisation in the corneal
      stroma. To understand the inter-relationships between proteoglycans and collagen
      fibrils in the cornea, adult mouse corneas were treated with cuprolinic blue and
      three-dimensional reconstructions of the anterior, mid and posterior corneal
      stroma were obtained. The reconstructions show regular diameters of collagen
      fibrils throughout the cornea and uniform interfibrillar spacing within each
      region. Both longitudinal and transverse reconstructions were obtained to
      establish a clear picture of proteoglycan organisation, yet no distinct regular
      pattern or symmetry of proteoglycan orientation was observed. Large, electron
      dense proteoglycans (possibly chondroitin sulphate/dermatan sulphate
      proteoglycans) interconnecting two or often three adjacent collagen fibrils are
      seen, whilst another sub-population of smaller proteoglycans (of the keratan
      sulphate variety) interconnect only neighbouring fibrils. The reconstructions
      suggest a complex interaction between proteoglycans and collagen, which allows
      for the dynamic control of collagen fibril architecture in the cornea.

PMID- 20132891
TI  - The shape of motor resonance: right- or left-handed?
AB  - The human mirror neuron system is a fronto-parietal neural pathway which, when
      activated by action observation, gives rise to an internal simulation of the
      observed action (motor resonance). Here we demonstrate how handedness shapes the
      resonant response, by engaging right-handed (RH) and left-handed (LH) subjects in
      observation and execution of actions preferentially performed by the dominant
      hand. We hypothesize that since motor resonance reproduces subliminally the
      specific motor program for the observed action, it should be subject to motor
      constraints, such as handedness. A conjunction analysis for observed and executed
      actions revealed that handedness determines a lateralized activation of the areas
      engaged in motor resonance. Premotor-BA6 and parietal-BA40 are strongly left
      lateralized in RH subjects observing or moving their right hand, and to a lesser
      degree their left hand. Extremely LH subjects show a similar pattern of
      lateralization on the right, while more ambidextrous LH subjects show a more
      bilateral activation. The activation of a cortical network outside the mirror
      neuron system is also discussed.

PMID- 20132892
TI  - A dynamic causal model study of neuronal population dynamics.
AB  - In this paper, we compare mean-field and neural-mass models of
      electrophysiological responses using Bayesian model comparison. In previous work,
      we presented a mean-field model of neuronal dynamics as observed with
      magnetoencephalography and electroencephalography. Unlike neural-mass models,
      which consider only the mean activity of neuronal populations, mean-field models
      track the distribution (e.g., mean and dispersion) of population activity. This
      can be important if the mean affects the dispersion or vice versa. Here, we
      introduce a dynamical causal model based on mean-field (i.e., population density)
      models of neuronal activity, and use it to assess the evidence for a coupling
      between the mean and dispersion of hidden neuronal states using observed
      electromagnetic responses. We used Bayesian model comparison to compare
      homologous mean-field and neural-mass models, asking whether empirical responses
      support a role for population variance in shaping neuronal dynamics. We used the
      mismatch negativity (MMN) and somatosensory evoked potentials (SEP) as
      representative neuronal responses in physiological and non-physiological
      paradigms respectively. Our main conclusion was that although neural-mass models
      may be sufficient for cognitive paradigms, there is clear evidence for an effect
      of dispersion at the high levels of depolarization evoked in SEP paradigms. This
      suggests that (i) the dispersion of neuronal states within populations generating
      evoked brain signals can be manifest in observed brain signals and that (ii) the
      evidence for their effects can be accessed with dynamic causal model comparison.

PMID- 20132893
TI  - Complexity analysis of source activity underlying the neuromagnetic somatosensory
      steady-state response.
AB  - Using the notion of complexity and synchrony, this study presents a data-driven
      pipeline of nonlinear analysis of neuromagnetic sources reconstructed from human
      magnetoencephalographic (MEG) data collected in reaction to vibrostimulation of
      the right index finger. The dynamics of MEG source activity was reconstructed
      with synthetic aperture magnetometry (SAM) beam-forming technique. Considering
      brain as a complex system, we applied complexity-based tools to identify brain
      areas with dynamic patterns that remain regular across repeated stimulus
      presentations, and to characterize their synchronized behavior. Volumetric maps
      of brain activation were calculated using sample entropy as a measure of signal
      complexity. The complexity analysis identified activity in the primary
      somatosensory (SI) area contralateral to stimuli and bilaterally in the posterior
      parietal cortex (PPC) as regions with decreased complexity, consistently
      expressed in a group of subjects. Seeding an activated source with low complexity
      in the SI area, cross-sample entropy was used to generate synchrony maps. Cross
      sample entropy analysis confirmed the synchronized dynamics of neuromagnetic
      activity between areas SI and PPC, robustly expressed across subjects. Our
      results extend the understanding of synchronization between co-activated brain
      regions, focusing on temporal coordination between events in terms of
      synchronized multidimensional signal patterns.

PMID- 20132894
TI  - Microstructural connectivity of the arcuate fasciculus in adolescents with high
      functioning autism.
AB  - The arcuate fasciculus is a white matter fiber bundle of great importance in
      language. In this study, diffusion tensor imaging (DTI) was used to infer white
      matter integrity in the arcuate fasciculi of a group of subjects with high
      functioning autism and a control group matched for age, handedness, IQ, and head
      size. The arcuate fasciculus for each subject was automatically extracted from
      the imaging data using a new volumetric DTI segmentation algorithm. The results
      showed a significant increase in mean diffusivity (MD) in the autism group, due
      mostly to an increase in the radial diffusivity (RD). A test of the
      lateralization of DTI measurements showed that both MD and fractional anisotropy
      (FA) were less lateralized in the autism group. These results suggest that white
      matter microstructure in the arcuate fasciculus is affected in autism and that
      the language specialization apparent in the left arcuate of healthy subjects is
      not as evident in autism, which may be related to poorer language functioning.

PMID- 20132895
TI  - Nonlinear connectivity by Granger causality.
AB  - The communication among neuronal populations, reflected by transient synchronous
      activity, is the mechanism underlying the information processing in the brain.
      Although it is widely assumed that the interactions among those populations (i.e.
      functional connectivity) are highly nonlinear, the amount of nonlinear
      information transmission and its functional roles are not clear. The state of the
      art to understand the communication between brain systems are dynamic causal
      modeling (DCM) and Granger causality. While DCM models nonlinear couplings,
      Granger causality, which constitutes a major tool to reveal effective
      connectivity, and is widely used to analyze EEG/MEG data as well as fMRI signals,
      is usually applied in its linear version. In order to capture nonlinear
      interactions between even short and noisy time series, a few approaches have been
      proposed. We review them and focus on a recently proposed flexible approach has
      been recently proposed, consisting in the kernel version of Granger causality. We
      show the application of the proposed approach on EEG signals and fMRI data.

PMID- 20132896
TI  - Linking brain-wide multivoxel activation patterns to behaviour: Examples from
      language and math.
AB  - A key goal of cognitive neuroscience is to find simple and direct connections
      between brain and behaviour. However, fMRI analysis typically involves choices
      between many possible options, with each choice potentially biasing any brain
      behaviour correlations that emerge. Standard methods of fMRI analysis assess each
      voxel individually, but then face the problem of selection bias when combining
      those voxels into a region-of-interest, or ROI. Multivariate pattern-based fMRI
      analysis methods use classifiers to analyse multiple voxels together, but can
      also introduce selection bias via data-reduction steps as feature selection of
      voxels, pre-selecting activated regions, or principal components analysis. We
      show here that strong brain-behaviour links can be revealed without any voxel
      selection or data reduction, using just plain linear regression as a classifier
      applied to the whole brain at once, i.e. treating each entire brain volume as a
      single multi-voxel pattern. The brain-behaviour correlations emerged despite the
      fact that the classifier was not provided with any information at all about
      subjects' behaviour, but instead was given only the neural data and its condition
      labels. Surprisingly, more powerful classifiers such as a linear SVM and
      regularised logistic regression produce very similar results. We discuss some
      possible reasons why the very simple brain-wide linear regression model is able
      to find correlations with behaviour that are as strong as those obtained on the
      one hand from a specific ROI and on the other hand from more complex classifiers.
      In a manner which is unencumbered by arbitrary choices, our approach offers a
      method for investigating connections between brain and behaviour which is simple,
      rigorous and direct.

PMID- 20132897
TI  - The neural implementation of task rule activation in the task-cuing paradigm: an
      event-related fMRI study.
AB  - To isolate the neural correlates for task rule activation from those related to
      general task preparation, the effect of a cue explicitly specifying the S-R
      correspondences (rule-cue) was contrasted with the effects of a cue specifying
      only the task to performed (task-cue). While the task-cue provides merely
      information about the type of task, the rule-cue is explicit about both the task
      type and the task rule (i.e., the set of S-R correspondences). The rule-cue was
      expected to activate the task rule more efficiently in the preparation period
      (prior to target presentation); by contrast, in the task-cue condition, part of
      the task rule activation was expected to be postponed into the task execution
      period (following the presentation of the target). In an event-related fMRI
      experiment, we found the right anterior and middle parts of the middle frontal
      and superior frontal gyri, the right inferior frontal junction, the pre-SMA, as
      well as the right superior and inferior parietal lobes to show larger activation
      elicited by the rule-cue than by the task-cue prior to target presentation.
      Conversely, the results revealed larger activations in these regions in the task
      cue than in the rule-cue condition during the task execution period. In summary,
      this study identified some of the neural correlates of task rule activation and
      showed that these are a subset of the general task preparation network.

PMID- 20132898
TI  - Phylogeny and biogeography of Philippine bent-toed geckos (Gekkonidae:
      Cyrtodactylus) contradict a prevailing model of Pleistocene diversification.
AB  - In the Philippines, Pleistocene sea level oscillations repeatedly connected and
      isolated neighboring islands. Hence, an understanding of the island platforms
      adjoined during periods of low sea level has led biologists to a suite of
      expectations that, taken together, represent a paradigm for the process of recent
      diversification in southeast Asia. We employ statistical tests of phylogenetic
      topology and population genetic analyses of widespread species of bent-toed
      geckos (Cyrtodactylus) to ascertain whether patterns of inter- and intra-specific
      diversity can be explained by a Pleistocene aggregate island model of
      diversification. Contrary to many classic studies of Philippine vertebrates, we
      find complex patterns that are only partially explained by past island
      connectivity. In particular, we determine that some populations inhabiting
      previously united island groups show substantial genetic divergence and are
      inferred to be polyphyletic. Additionally, greater genetic diversity is found
      within islands, than between them. Among the topological patterns inconsistent
      with the Pleistocene model, we note some similarities with other lineages, but no
      obviously shared causal mechanisms are apparent. Finally, we infer well-supported
      discordance between the gene trees inferred from mitochondrial and nuclear DNA
      sequences of two species, which we suspect is the result of incomplete lineage
      sorting. This study contributes to a nascent body of literature suggesting that
      the current paradigm for Philippine biogeography is an oversimplification
      requiring revision.

PMID- 20132899
TI  - Molecular phylogeny of slug-parasitic nematodes inferred from 18S rRNA gene
      sequences.
AB  - Terrestrial molluscs are diverse and are infected by many nematodes. We propose a
      phylogeny of slug-parasitic nematodes using 18S rRNA gene sequences from
      nematodes isolated from slugs collected from six countries. Eight species,
      representing six families of nematodes were identified and trees inferred placed
      them within four (I, III, IV and V) out of the five clades of Nematoda,
      indicating multiple origins of slug parasitism. Five species representing three
      families formed a monophyletic group in clade V. Although these species are
      closely related, their morphology has changed greatly, suggesting adaptive
      radiation to fill different niches within the host.

PMID- 20132900
TI  - Phylogeography of Chinese bamboo partridge, Bambusicola thoracica thoracica
      (Aves: Galliformes) in south China: inference from mitochondrial DNA control
      region sequences.
AB  - Chinese bamboo partridge (Bambusicola thoracica thoracica), an endemic subspecies
      of south China, distributes in mountainous areas that were affected by climate
      changes throughout the Pleistocene. We investigated the potential impact of
      cyclical Pleistocene climate changes on phylogeographic patterns using 1140
      nucleotides of mitochondrial DNA (mtDNA) control-region from 180 individuals
      sampled from 13 populations of the partridge. We found 50 haplotypes defined by
      39 polymorphic positions. Phylogenetic analyses revealed two robustly supported
      clades. There was a significant genetic differentiation among the populations
      with little gene flow. Refugia were identified in the southwestern mountains and
      Luoxiao Mountains in China, implying that topographic complexity played a
      substantial role in providing suitable habitats for the partridge during cold
      periods. Results from the mismatch distribution and neutrality test analysis
      suggested a range expansion of the two clades. The mtDNA marker suggested the
      existence of a geographical structure among Chinese bamboo partridge populations,
      resulting from the synergistic affect of Pleistocene climatic variations.

PMID- 20132901
TI  - PISA, a novel pharmacodynamic assay for assessing poly(ADP-ribose) polymerase
      (PARP) activity in situ.
AB  - INTRODUCTION: Poly ADP-ribose polymerase (PARP) maintains genomic integrity by
      repairing DNA strand breaks, however over-activation of PARP following neural
      tissue injury is hypothesized to cause neuronal death. Therefore, PARP inhibitors
      have potential for limiting neural injury under certain conditions. A reliable
      method for assessing PARP activity in brain is critical for development of novel
      inhibitors with CNS activity. We developed the PARP In Situ Activity (PISA) assay
      to provide a direct, quantitative assessment of CNS PARP activity in vitro or in
      vivo. METHODS: The assay utilized brain sections from rats with striatal kainic
      acid (KA) lesions and 3H- or biotinylated NAD+ as the substrate to assess PARP
      activity. Following optimization of the assay, it was used to assess in vitro and
      in vivo efficacy of known and novel PARP inhibitors. The assay also was used to
      assess PARP activity in male and female gonad-intact and ovariectomized rats.
      RESULTS: Using 3H-NAD+ as the substrate, PARP activity was greater (p<0.01) in
      tissue from KA-lesioned vs. non-lesioned rats. Using biotinylated NAD+ it was
      revealed that PARP activity was present ipsilateral to the KA injection site, and
      labeling was blocked by incubation with excess unlabeled NAD+ or PARP inhibitors.
      The PARP inhibitor, 3-aminobenzamide and several novel inhibitors reduced
      (p<0.01) polymerase activity in vitro. Furthermore, the inhibitor MRLSD303
      reduced (p<0.001) PARP activity in vivo in both male and female rats. Finally,
      administration of the novel PARP inhibitor MRLIT115 dose-dependently reduced
      (p<0.001) polymerase activity in vivo. DISCUSSION: The PISA assay provides a
      direct, quantitative method for assessing PARP activity in vitro and provides
      critical information on factors underlying in vivo efficacy of chemical
      inhibitors including brain penetration and target engagement. These findings
      support use of the PISA assay as a screening tool for testing efficacy of PARP
      inhibitors in brain.

PMID- 20132902
TI  - Role of the primary somatosensory cortex in motor learning: An rTMS study.
AB  - Somatosensation is thought to play an important role in skilled motor learning.
      The present study investigated how healthy adults learn a continuous implicit
      motor task when somatosensation is altered by 1 Hz repetitive transcranial
      magnetic stimulation (rTMS) delivered over the primary somatosensory cortex (S1).
      Twenty-seven right-handed participants enrolled in a two-part experiment. In
      Experiment 1, we verified that 20 min of 1 Hz rTMS over S1 disrupted cutaneous
      somatosensation (indexed by two-point discrimination) in the wrist/hand; the
      impact of 1 Hz rTMS on wrist proprioception (tested by limb-position matching)
      was variable. Sham rTMS had no effect on either measure. We exploited these
      effects in Experiment 2 by pairing either 1 Hz or sham rTMS with practice of a
      continuous tracking task over two separate sessions on different days. Implicit
      motor learning was indexed on a third, separate retention test day when no rTMS
      was delivered. Across practice in Experiment 2, both the 1 Hz and sham rTMS
      groups showed improved tracking performance; however, 1 Hz rTMS was associated
      with less accurate tracking and smaller improvements in performance. Importantly,
      at the no rTMS retention test the effects of altering sensation with stimulation
      over S1 were still evident in the persistently less accurate tracking behavior of
      the 1 Hz rTMS group. The current study shows that disruption of somatosensation
      during task practice impairs the magnitude of change associated with motor
      learning, perhaps through the development of an inaccurate internal model.

PMID- 20132903
TI  - SLV330, a cannabinoid CB1 receptor antagonist, ameliorates deficits in the T
      maze, object recognition and Social Recognition Tasks in rodents.
AB  - Cannabinoid CB(1) receptor (CB(1)R) signaling has been suggested to play an
      important role in the regulation of memory and cognition. In the present study,
      our aim was to investigate whether the CB(1)R antagonist SLV330 (doses ranging
      from 0.3 to 10mg/kg, given orally, p.o.) could ameliorate impairments in distinct
      aspects of cognition using different disruption models in both mice and rats.
      Effects of SLV330 were tested on working memory deficits in the T-maze Continuous
      Alternation Task (T-CAT) in mice; episodic memory deficits in the Object
      Recognition Task (ORT) and Social Recognition Task (SRT) in rats. The
      acetylcholinesterase inhibitor (AChEI) donepezil (Aricept, approved for
      symptomatic treatment of Alzheimer's disease) and nicotine were used as reference
      compounds. SLV330 markedly improved aging and scopolamine-induced memory deficits
      in the T-CAT in mice with a lowest effective dose (LED) of 1mg/kg p.o., while
      reversing the cognitive dysfunction induced by the N-methyl-D-aspartate (NMDA)
      antagonist dizocilpine (MK-801) only at the middle dose of 3mg/kg. In the ORT, we
      have found that combined administration of subthreshold doses of SLV330 (1mg/kg,
      p.o.) and the AChEI donepezil (0.1mg/kg, p.o.), that had no discernable effects
      on performance when given alone, enhanced memory performance in Wistar rats with
      deficits induced by the muscarinic antagonist scopolamine, suggestive of additive
      synergistic effects of SLV330 and donepezil on cognitive impairment. Finally,
      SLV330 was found to have cognition enhancing properties in a time delay paradigm
      in the SRT at a LED dose of 3mg/kg (p.o.). In conclusion, the CB(1)R antagonist
      SLV330 was found to clearly improve memory in several preclinical models for
      cognitive impairment.

PMID- 20132904
TI  - Analysis of structure and gene expression of bovine CCDC3 gene indicates a
      function in fat metabolism.
AB  - Our study reports the molecular analysis of the bovine gene encoding the coiled
      coil domain-containing protein 3 (CCDC3). Based on comparative sequence analysis
      and in silico sequence merging of predicted gene models, a new full-length gene
      model for the bovine CCDC3 gene was predicted and confirmed experimentally. The
      CCDC3 gene was assigned to bovine chromosome 13. It consists of three exons
      comprising 2599bp encoding for a respective protein of 274 amino acids. The
      strong CCDC3 sequence homology on amino acid level between species suggests a
      conserved universal function of this protein. In mice, the CCDC3 gene had been
      found to be highly expressed in adipocytes and regulated by hormonal-nutritional
      alternations and in obesity. The tissue expression pattern of bovine CCDC3 mRNA
      indicates a ubiquitous physiological function of the gene. Significant
      differences in CCDC3 mRNA expression in skeletal muscle between individuals
      characterized by divergent intramuscular fat deposition support the potential
      function of the gene in fat or energy metabolism, which possibly could also be
      inferred for other mammalian species. This first report of structural analysis
      and molecular characterization of the CCDC3 gene in cattle will contribute to a
      better understanding of the yet unknown physiological role of the respective
      protein in mammals.

PMID- 20132905
TI  - Momordicatin purified from fruits of Momordica charantia is effective to act as a
      potent antileishmania agent.
AB  - Aqueous extract of the green fruits of the Indian plant Momordica charantia and
      purified Momordicatin structurally established as 4-(o-carboethoxyphenyl) butanol
      were evaluated in vitro and in vivo against kala-azar caused by Leishmania
      donovani. 50% inhibitory concentration (IC(50)) against Leishmania promastigotes
      in vitro for the crude extract and momordicatin were 0.6mg/L and 0.02mg/L,
      respectively. When administered in the hamster model of visceral leishmaniasis,
      100% parasite clearance was achieved at a dose of 300mg/kg body weight of crude
      extract and 10mg/kg body weight of Momordicatin. Fe containing parasite
      superoxide dismutase (SOD) was totally inhibited when treated with 0.72mg/L crude
      extract and 0.20mg/L Momordicatin, respectively, whereas Cu-Zn containing SOD
      present in host remained unaffected. Results reveal that the mode of action of
      these newly found antileishmanial agents is mediated through inhibiting parasite
      SOD which is one of the key enzymes of the oxidative burst. It may be proposed
      from the present study that both crude extract of Momordica charantia and
      Momordicatin obtained from the fruits of the said plant may be considered as
      potential candidates towards developing new chemotherapeutics against
      leishmaniasis.

PMID- 20132906
TI  - Evidence for proteolytic processing and stimulated organelle redistribution of
      iPLA(2)beta.
AB  - Over the past decade, important roles for the 84-88kDa Group VIA Ca(2+)
      independent phospholipase A(2) (iPLA(2)beta) in various organs have been
      described. We demonstrated that iPLA(2)beta participates in insulin secretion,
      insulinoma cells and native pancreatic islets express full-length and truncated
      isoforms of iPLA(2)beta, and certain stimuli promote perinuclear localization of
      iPLA(2)beta. To gain a better understanding of its mobilization, iPLA(2)beta was
      expressed in INS-1 cells as a fusion protein with EGFP, enabling detection of
      subcellular localization of iPLA(2)beta by monitoring EGFP fluorescence. Cells
      stably-transfected with fusion protein expressed nearly 5-fold higher catalytic
      iPLA(2)beta activity than control cells transfected with EGFP cDNA alone,
      indicating that co-expression of EGFP does not interfere with manifestation of
      iPLA(2)beta activity. Dual fluorescence monitoring of EGFP and organelle Trackers
      combined with immunoblotting analyses revealed expression of truncated
      iPLA(2)beta isoforms in separate subcellular organelles. Exposure to
      secretagogues and induction of ER stress are known to activate iPLA(2)beta in
      beta-cells and we find here that these stimuli promote differential localization
      of iPLA(2)beta in subcellular organelles. Further, mass spectrometric analyses
      identified iPLA(2)beta variants from which N-terminal residues were removed.
      Collectively, these findings provide evidence for endogenous proteolytic
      processing of iPLA(2)beta and redistribution of iPLA(2)beta variants in
      subcellular compartments. It might be proposed that in vivo processing of
      iPLA(2)beta facilitates its participation in multiple biological processes.

PMID- 20132907
TI  - State-of-the-art Echinococcus and Taenia: phylogenetic taxonomy of human
      pathogenic tapeworms and its application to molecular diagnosis.
AB  - The taxonomy of tapeworms belonging to the family Taeniidae has been
      controversial because of the paucity of adult phenotypic characters and the great
      plasticity of larvae in intermediate hosts. The family consists of the medically
      important two genera Echinococcus and Taenia, which are closely related to each
      other. Cladistic approaches using the molecular data of DNA and the numerical
      data of morphologic characters are clarifying phylogenetic relationships among
      the members of these genera. The nucleotide data of worldwide taeniid parasites
      accumulated in public DNA databases may provide a basis for the development of
      molecular diagnostic tools, and make it possible to identify the parasites, at
      least the human Taenia spp. by non-morphologists. Furthermore, the detection of
      intraspecific genetic variations prompts evolutionary and ecological studies to
      address fundamental questions of parasite distributional patterns. Here, we
      introduce the recent advances of taeniid phylogeny and its application to
      molecular diagnosis.

PMID- 20132908
TI  - Lymphatic filarial species differentiation using evolutionarily modified tandem
      repeats: generation of new genetic markers.
AB  - Polymerase chain reaction based methods are promising tools for the monitoring
      and evaluation of the Global Program for the Elimination of Lymphatic Filariasis.
      The currently available PCR methods do not differentiate the DNA of Wuchereria
      bancrofti or Brugia malayi by a single PCR and hence are cumbersome. Therefore,
      we designed a single step PCR strategy for differentiating Bancroftian infection
      from Brugian infection based on a newly identified gene from the W. bancrofti
      genome, abundant larval transcript-2 (alt-2), which is abundantly expressed. The
      difference in PCR product sizes generated from the presence or absence of
      evolutionarily altered tandem repeats in alt-2 intron-3 differentiated W.
      bancrofti from B. malayi. The analysis was performed on the genomic DNA of
      microfilariae from a number of patient blood samples or microfilariae positive
      slides from different Indian geographical regions. The assay gave consistent
      results, differentiating the two filarial parasite species accurately. This alt-2
      intron-3 based PCR assay can be a potential tool for the diagnosis and
      differentiation of co-infections by lymphatic filarial parasites.

PMID- 20132909
TI  - Sirtuin chemical mechanisms.
AB  - Sirtuins are ancient proteins widely distributed in all lifeforms of earth. These
      proteins are universally able to bind NAD(+), and activate it to effect ADP
      ribosylation of cellular nucleophiles. The most commonly observed sirtuin
      reaction is the ADP-ribosylation of acetyllysine, which leads to NAD(+)-dependent
      deacetylation. Other types of ADP-ribosylation have also been observed, including
      protein ADP-ribosylation, NAD(+) solvolysis and ADP-ribosyltransfer to 5,6
      dimethylbenzimidazole, a reaction involved in eubacterial cobalamin biosynthesis.
      This review broadly surveys the chemistries and chemical mechanisms of these
      enzymes.

PMID- 20132910
TI  - A non-steroidal anti-inflammatory drug (ketoprofen) does not delay beta-TCP bone
      graft healing.
AB  - Beta-tricalcium phosphate (beta-TCP) is a suitable biomaterial in oral and
      maxillofacial surgery since it can induce a rapid proliferation of woven bone.
      Granules, prepared by the polyurethane foam method, were implanted in critical
      size defects performed in the femoral condyles of New Zealand rabbits. Animals
      were studied after 8 and 28 days. Ketoprofen (a non-steroidal anti-inflammatory
      drug (NSAID)) was given for 8 and 28 days to evaluate its effects on the healing
      of the graft. Before euthanasia, the rabbits received an intravenous injection of
      fluorescent microbeads. Bones were analyzed by microcomputed tomography. beta-TCP
      granules induced metaplastic bone trabeculae as early as 8 days post-surgery. At
      28 days, the amount of bone was increased and the biomaterial volume decreased
      due to simultaneous macrophagic resorption. The amount of macrophages labeled
      with microbeads was less in the grafted area than in the vicinal intact marrow
      spaces. Ketoprofen had no effect on the amount of bone formed and on the number
      of labeled macrophages. The influence of small doses of NSAID, given in a short
      duration period, did not present deleterious effects on bone graft healing.

PMID- 20132911
TI  - Fluoride-containing bioactive glasses: effect of glass design and structure on
      degradation, pH and apatite formation in simulated body fluid.
AB  - Bioactive glasses are able to bond to bone through formation of carbonated
      hydroxyapatite in body fluids, and fluoride-releasing bioactive glasses are of
      interest for both orthopaedic and, in particular, dental applications for caries
      inhibition. Melt-derived glasses in the system SiO(2)-P(2)O(5)-CaO-Na(2)O with
      increasing amounts of CaF(2) were prepared by keeping network connectivity and
      the ratio of all other components constant. pH change, ion release and apatite
      formation during immersion of glass powder in simulated body fluid at 37 degrees
      C over up to 2 weeks were investigated. Crystal phases formed in SBF were
      characterized using infrared spectroscopy, X-ray diffraction with Rietveld
      analysis and solid-state nuclear magnetic resonance spectroscopy ((19)F and (31)P
      MAS-NMR). Results show that incorporation of fluoride resulted in a reduced pH
      rise in aqueous solutions compared to fluoride-free glasses and in formation of
      fluorapatite (FAp), which is more chemically stable than hydroxyapatite or
      carbonated hydroxyapatite and therefore is of interest for dental applications.
      However, for increasing fluoride content in the glass, fluorite (CaF(2)) was
      formed at the expense of FAp. Apatite formation could be favoured by increasing
      the phosphate content in the glass, as the release of additional phosphate into
      the SBF would affect supersaturation in the solution and possibly favour
      formation of apatite.

PMID- 20132912
TI  - Porous tantalum structures for bone implants: fabrication, mechanical and in
      vitro biological properties.
AB  - The relatively high cost of manufacturing and the inability to produce modular
      implants have limited the acceptance of tantalum, in spite of its excellent in
      vitro and in vivo biocompatibility. In this article, we report how to process Ta
      to create net-shape porous structures with varying porosity using Laser
      Engineered Net Shaping (LENS) for the first time. Porous Ta samples with relative
      densities between 45% and 73% have been successfully fabricated and characterized
      for their mechanical properties. In vitro cell materials interactions, using a
      human fetal osteoblast cell line, have been assessed on these porous Ta
      structures and compared with porous Ti control samples. The results show that the
      Young's modulus of porous Ta can be tailored between 1.5 and 20 GPa by changing
      the pore volume fraction between 27% and 55%. In vitro biocompatibility in terms
      of MTT assay and immunochemistry study showed excellent cellular adherence,
      growth and differentiation with abundant extracellular matrix formation on porous
      Ta structures compared to porous Ti control. These results indicate that porous
      Ta structures can promote enhanced/early biological fixation. The enhanced in
      vitro cell-material interactions on the porous Ta surface are attributed to its
      chemistry, its high wettability and its greater surface energy relative to porous
      Ti. Our results show that these laser-processed porous Ta structures can find
      numerous applications, particularly among older patients, for metallic implants
      because of their excellent bioactivity.

PMID- 20132913
TI  - Sucrose esters with various hydrophilic-lipophilic properties: novel controlled
      release agents for oral drug delivery matrix tablets prepared by direct
      compaction.
AB  - Sucrose esters (SE) are esters of sucrose and fatty acids with various
      hydrophilic-lipophilic properties which have attracted interest from being used
      in pharmaceutical applications. This study aimed to gain insight into the use of
      SE as controlled release agents for direct compacted matrix tablets. The study
      focused on the effect of hydrophilic-lipophilic properties on tableting
      properties and drug release. Sucrose stearate with hydrophilic-lipophilic balance
      (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations
      contained SE, metoprolol tartrate as a highly soluble model drug and dibasic
      calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2.
      The compaction behaviour of matrix tablets was compared with the compacts of
      individual starting materials as reference. SE incorporation improved the
      plasticity, compressibility and lubricating property of powder mixtures. The
      hydrophilic-lipophilic properties of SE affected tableting properties, drug
      release rate and release mechanism. Increasing hydrophilicity corresponding to
      the increased monoesters in SE composition increased the relative porosity,
      elastic recovery and tensile strength of the tablets due to the increased
      hydrogen bonding between the monoesters. This also facilitated the swelling
      behaviour of SE, which sustained the drug release rate. A sustained release
      effect prevailed in tablets containing SE with HLB values of 3-16. The ability to
      improve the tableting properties as well as sustain the drug release rate of the
      highly soluble model drug via gelation of SE highlights SE as promising
      controlled release regulators for direct compacted matrix tablets comprising
      drugs with various solubilities according to the Biopharmaceutics Classification
      System.

PMID- 20132914
TI  - Role of routine oesophago-gastroduodenoscopy before cholecystectomy.
AB  - INTRODUCTION: A proportion of patients do not get symptomatic relief after
      cholecystectomy because there is an overlap in the symptomology of biliary and
      gasroduodenal pathologies. In our unit all the patients are offered gastroscopy
      prior to Cholecystectomy. Aim of this study was to evaluate the efficacy of
      gastroscopy in all patients with upper abdominal pain irrespective of ultrasound
      findings. MATERIAL AND METHODS: This retrospective study was carried out, between
      Jan 2001-Oct 2003. All the patients undergoing laparoscopic cholecystectomy by a
      single surgeon were studied. Group 1 (n = 61) were not endoscoped before the
      operation (Jan 2001-May 2002). Group 2 (n = 60) had routine endoscopy carried out
      before surgery (June 2002-October 2003). The results were entered in a database
      and analyzed. RESULTS: Total of 240 laparoscopic cholecystectomies were carried
      out. Female to male ratio was 4:1. In Group 1, the recurrence or persistence of
      symptoms was 20/61 (32.78%) patients who were not scoped. In Group 2, all
      patients were scoped with positive findings in 35% of the patients. All were
      treated for the pathology and only 2(3.3%) had recurrence or persistence of
      symptoms. CONCLUSION: The routine use of gastroscopy before laparoscopic
      cholecystectomy helps to reduce persistence of symptoms and is recommended.

PMID- 20132915
TI  - A 5-year prospective review of posterior partial fundoplication in the management
      of gastroesophageal reflux disease.
AB  - INTRODUCTION: Laparoscopic Nissen fundoplication is the most common surgical
      procedure performed for gastroesophageal reflux disease (GORD). It is however
      associated with a number of mechanical complications with as many as one in three
      patients experiencing troublesome dysphagia or gas bloat. Partial fundoplication,
      either posterior or anterior, has been advocated in an attempt to reduce these
      problems. Our aim was to prospectively evaluate laparoscopic posterior partial
      (Toupet) fundoplication as the primary surgical treatment for GORD. METHOD:
      Outcomes following Toupet fundoplication performed between October 2002 and
      October 2007 were recorded prospectively. All patients underwent a 270 degrees
      posterior partial fundoplication with routine crural repair. All procedures were
      performed by a single surgeon. Pre-operative investigations included endoscopy,
      pH studies/manometry and contrast studies. DeMeester acidity scores, percentage
      reflux time and oesophageal motility were recorded. Pre- and post-operative
      DeMeester symptom scores (0-9, DSS) and Visick grading were used to assess the
      outcomes of surgery. RESULTS: 101 Patients were studied. Ages ranged from 17 to
      69 years. The median pre-operative DSS of 5 fell to a median of 0 post
      operatively. Scores decreased following surgery in all cases. 91 (91%) patients
      were discharged on the 2nd post-operative day or sooner. 5 (4.9%) patients had
      prolonged dysphagia (>3 months), and 8 (7.9%) had mild prolonged gas bloat. A
      single patient had a recurrence of reflux at 2 years and required re-do
      laparoscopic surgery. There were no conversions to open surgery. CONCLUSIONS:
      Laparoscopic Toupet fundoplication provides excellent relief of GORD symptoms
      with a low incidence of post-operative mechanical complications. We would
      recommend it as the operation of choice for GORD.

PMID- 20132916
TI  - Harmonic Scalpel compared with bipolar electro-cautery hemorrhoidectomy: a
      randomized controlled trial.
AB  - INTRODUCTION: Surgical excision using Harmonic Scalpel is a modern technique used
      for ablation of symptomatic third degree and all fourth-degree hemorrhoids.
      Compared with electrocautery, Harmonic Scalpel causes minimal lateral thermal
      injury during tissue dissection. The resulting mucosal defect is then either left
      open or sutured (closed) depending on surgeon preference. The aim of this work
      was to evaluate the value of using Harmonic Scalpel in reducing incidence of
      postoperative complications following Hemorrhoidectomy. PATIENTS & METHODS: This
      is a single-blind randomized controlled trial done at Zagazig University hospital
      during the period from July 2007 to December 2008. Patients underwent surgical
      excision of complex grade III or grade IV hemorrhoids. They were divided into two
      groups: (A) Harmonic Scalpel Hemorrhoidectomy group and (B) Bipolar Electro
      cautery Hemorrhoidectomy group. Pain levels scoring and postoperative
      complications were analyzed. RESULTS: Postoperative pain in Group (A) was
      significantly less with less analgesic requirement. There was no significant
      difference between both groups regarding other postoperative complications.
      CONCLUSION: This study demonstrates significantly reduced postoperative pain
      after Harmonic Scalpel Hemorrhoidectomy compared with bipolar electro-cautery
      Hemorrhoidectomy. Most likely, this result came from the avoidance of excessive
      lateral thermal injury caused by bipolar electrocautery.

PMID- 20132917
TI  - Characterization of a de novo balanced translocation t(9;18)(p23;q12.2) in a
      patient with oculoauriculovertebral spectrum.
AB  - We report a patient presenting with oculoauriculovertebral spectrum and a de novo
      balanced reciprocal translocation t(9;18)(p23;q12.2). Physical mapping of the
      translocation breakpoints by fluorescent in situ hybridization showed that the
      breakpoints are located in two regions encompassing gene deserts. An additional
      paternally inherited duplication in 18p11.23p11.31 was identified by array-CGH.
      We discuss the possible involvement of these chromosomal abnormalities in OAVS.

PMID- 20132918
TI  - Interstitial microduplication of Xp22.31: Causative of intellectual disability or
      benign copy number variant?
AB  - The use of comparative genomic hybridization (CGH) and single nucleotide
      polymorphism (SNP) arrays has dramatically altered the approach to identification
      of genetic alterations that can explain intellectual disability and /or
      congenital anomalies. However, the discovery of numerous copy number changes with
      benign or unknown clinical significance has made interpretation problematic.
      Submicroscopic duplication of Xp22.31 has been reported as either a possible
      cause of intellectual disability and/or developmental delay or a benign variant.
      Here we report 29 individuals with the microduplication found as part of
      microarray analysis of 7793 samples submitted to an international group of 13
      clinical laboratories. The referral reasons varied and included developmental
      delay, intellectual disability, autism, dysmorphic features and/or multiple
      congenital anomalies. The size of the Xp22.31 duplication varied between 149 kb
      and 1.74 Mb and included the steroid sulfatase (STS) gene with the male to female
      ratio of 0.7. Duplication within this segment is seen at a frequency of 0.15% in
      a healthy control population, whereas a frequency of 0.37% was observed in our
      cohort of individuals with abnormal phenotypes. We present a detailed comparison
      of the breakpoints, inheritance, X-inactivation and clinical phenotype in our
      cohort and a review of the literature for a total of 41 patients. To date, this
      report is the largest compilation of clinical and array data regarding the
      microduplication of Xp22.31 and will serve to broaden the knowledge of regions
      involving copy number variation (CNV).

PMID- 20132919
TI  - Efficacy of inactivated swine influenza virus vaccines against the 2009 A/H1N1
      influenza virus in pigs.
AB  - The gene constellation of the 2009 pandemic A/H1N1 virus is a unique combination
      from swine influenza A viruses (SIV) of North American and Eurasian lineages, but
      prior to April 2009 had never before been identified in swine or other species.
      Although its hemagglutinin gene is related to North American H1 SIV, it is
      unknown if vaccines currently used in U.S. swine would cross-protect against
      infection with the pandemic A/H1N1. The objective of this study was to evaluate
      the efficacy of inactivated vaccines prepared with North American swine influenza
      viruses as well as an experimental homologous A/H1N1 vaccine to prevent infection
      and disease from 2009 pandemic A/H1N1. All vaccines tested provided partial
      protection ranging from reduction of pneumonia lesions to significant reduction
      in virus replication in the lung and nose. The multivalent vaccines demonstrated
      partial protection; however, none was able to prevent all nasal shedding or
      clinical disease. An experimental homologous 2009 A/H1N1 monovalent vaccine
      provided optimal protection with no virus detected from nose or lung at any time
      point in addition to amelioration of clinical disease. Based on cross-protection
      demonstrated with the vaccines evaluated in this study, the U.S. swine herd
      likely has significant immunity to the 2009 A/H1N1 from prior vaccination or
      natural exposure. However, consideration should be given for development of
      monovalent homologous vaccines to best protect the swine population thus limiting
      shedding and the potential transmission of 2009 A/H1N1 from pigs to people.

PMID- 20132920
TI  - Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus
      HA by a polyanionic carbomer.
AB  - Carbopol is a polyanionic carbomer gel used in man for a variety of topical
      applications and drug delivery purposes. Here we show that subcutaneous
      administration of carbopol with glycoprotein antigens elicits unusually strong
      specific adaptive immune responses in mice. Recombinant soluble HIV-1 envelope
      glycoprotein (Env)-based antigen formulated in carbopol was at least as potent at
      stimulating Env-specific B and T cell responses as Freund's Complete Adjuvant,
      and significantly more potent than aluminium salts. The antigen-specific T cell
      immune response elicited both Th1 and Th2 cytokines including high titers of IFN
      gamma, IL-2 and IL-4, and drove a Th1 isotype-switched antibody response. Mice
      immunized with a low dose of purified influenza HA in carbopol generated high
      titers of anti-HA antibodies and were protected from lethal challenge and disease
      with live virus. Similarly, immunization of mice with the melanoma cell line
      B16F10 formulated in carbopol significantly delayed tumor growth. We propose that
      carbopol, or related cross-linked polyacrylic acid analogues, may have promise
      for use as systemic vaccine adjuvants in man.

PMID- 20132921
TI  - Inpatient hospitalization for gynecologic disorders in the United States.
AB  - OBJECTIVE: The purpose of this study was to examine trends in hospitalizations
      for gynecologic disorders in the United States. STUDY DESIGN: Data on
      hospitalizations from 1998-2005 among women 15-54 years old were from the
      Nationwide Inpatient Sample, a nationally representative survey of inpatient
      hospitalizations. Hospitalizations with a principal diagnosis of a gynecologic
      disorder were used to estimate rates per 10,000 women. RESULTS: Gynecologic
      disorders accounted for 7% and 14% of all hospitalizations among women 15-44 and
      45-54 years old, respectively. The most common diagnoses were uterine leiomyomas
      (rate = 27.5), menstrual disorders (rate = 12.3), endometriosis (rate = 9.5),
      genital prolapse (rate = 7.0), benign ovarian cysts (rate = 6.5), and pelvic
      inflammatory disease (rate = 6.1). The hospitalization rate for menstrual
      disorders increased from 9.8 in 1998 to 13.3 in 2005 (P trend < .001). In
      contrast, rates declined for pelvic inflammatory disease, genital prolapse,
      benign ovarian cysts, and endometriosis (P trend < .05) and were unchanged for
      uterine leiomyoma. CONCLUSION: Gynecologic disorders are an important contributor
      to inpatient hospitalization among women in the United States.

PMID- 20132922
TI  - Recurrence of preterm premature rupture of membranes in relation to interval
      between pregnancies.
AB  - OBJECTIVE: The purpose of this study was to examine whether the recurrence risk
      of preterm premature rupture of membranes (PPROM) is modified by the
      interpregnancy interval (IPI). STUDY DESIGN: We used the Missouri 1989-1997
      longitudinally linked data to examine the recurrence risk of PPROM in women with
      first 2 (n = 150,929) and first 3 (n = 30,011) successive pregnancies. Race
      specific recurrence risks were examined. Adjusted odds ratios (ORs) were used to
      estimate risks. RESULTS: Risks of PPROM in the second pregnancy among women with
      and without previous PPROM were 5.7% and 2.3%, respectively, among white women
      (OR, 8.7; 95% confidence interval, 6.7-11.4) and 10.3% and 4.3%, respectively,
      among African American women (OR, 7.2; 95% confidence interval, 5.1-10.1). Short
      IPI was associated with increased risk for PPROM recurrence, with substantially
      higher risk for African American women than white women. However, long IPI was
      associated with increased recurrence among African American women. CONCLUSION:
      Women with previous PPROM are at increased risk for recurrence, and a short IPI
      is associated with increased risk.

PMID- 20132923
TI  - Association of maternal gestational weight gain with short- and long-term
      maternal and child health outcomes.
AB  - OBJECTIVE: The purpose of this study was to investigate the associations between
      gestational weight gain (GWG) and small- and large-for-gestational-age (SGA,
      LGA), cesarean delivery, child overweight, and maternal postpartum weight
      retention in a diverse sample of women in the Unites States. STUDY DESIGN: We
      estimated associations between GWG (continuous and within categories defined by
      the Institute of Medicine), maternal prepregnancy body mass index, and each
      outcome in 4496 births in the National Longitudinal Survey of Youth 1979, which
      was a prospective cohort. RESULTS: GWG (kilograms) was associated with decreased
      risk of SGA and increased risk of LGA, cesarean delivery, postpartum weight
      retention, and child overweight independent of maternal demographic and pregnancy
      characteristics. Gain above the Institute of Medicine guidelines was associated
      with decreased risk of SGA and increased risk of all other outcomes. CONCLUSION:
      Excessive gain may have long-term consequences for maternal and child body size,
      but the benefits of lower gain must be balanced against risk of SGA.

PMID- 20132924
TI  - Association between mannose-binding lectin levels and gene polymorphisms in
      chronic periodontitis and response to treatment.
AB  - BACKGROUND: The aims of the present study were: (1) to investigate mannose
      binding lectin (MBL) gene exon-1 polymorphisms in Turkish subjects with chronic
      periodontitis (CP), (2) to assess the association between these polymorphisms and
      plasma MBL levels, (3) to determine the effects of MBL genotypes on the outcomes
      of non-surgical periodontal therapy. METHODS: A total of 172 subjects were
      included in the present study. Genomic DNA was obtained from the peripheral blood
      of 83 CP patients and 89 periodontally healthy subjects. The MBL levels were
      measured by enzyme-linked immunosorbent assay (ELISA). The MBL gene exon-1
      polymorphisms were genotyped by the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. RESULTS: Subjects homozygous for
      the frequent allele A had higher MBL plasma levels compared with rare allele B
      carriers. This difference in MBL plasma levels was statistically significant both
      in CP patients and healthy subjects. The distribution of MBL gene codon 54
      genotypes and allele frequencies did not differ significantly between study
      groups. All study subjects were the MBL gene codon 52 and 57 frequent allele A
      carriers. Codon 54 B allele carriers had similar clinical periodontal parameters
      compared with AA genotypes after non-surgical periodontal therapy. CONCLUSIONS:
      The present study failed to find any significant association between the MBL gene
      codon 54 polymorphisms and severe CP in a Turkish population. MBL gene rare
      allele carriers had lower MBL plasma levels in both study groups. It seems that
      MBL gene codon 54 B allele carriage may not influence the outcome of periodontal
      therapy.

PMID- 20132925
TI  - Implicit self-esteem in recurrently depressed patients.
AB  - Negative self-esteem is suggested to play an important role in the recurrence of
      depressive episodes. This study investigated whether repeated experiences of a
      negative view of the self within a recurrent course of depression might cause
      implicit self-esteem to be impaired and negative self-attributes to even be
      chronically activated beyond remission. We measured implicit self-esteem using an
      Implicit Association Test. The sample consisted of N = 24 currently depressed
      patients with first-onset depressive episode, N = 28 currently depressed patients
      with recurrent depressive episodes, N = 33 currently remitted patients with
      recurrent depressive episodes, and N = 34 controls with no history of depression.
      In line with cognitive theories, results revealed significantly lower implicit
      self-esteem in current depressive patients than in healthy controls but no
      significant differences in implicit self-esteem between remitted recurrent
      depressive patients and healthy controls. However, remitted depressive patients
      with three or more depressive episodes showed a significantly lower implicit self
      esteem than those with less than three depressive episodes. The current findings
      underline the necessity of relapse prevention treatments which not only enhance
      self-esteem at an explicit but also at an implicit level as well as emphasizing
      the need for evaluations of treatment efficacy to focus upon both implicit and
      explicit levels of self-esteem.

PMID- 20132926
TI  - Alcohol-induced neurodegeneration, suppression of transforming growth factor
      beta, and cognitive impairment in rats: prevention by group II metabotropic
      glutamate receptor activation.
AB  - BACKGROUND: Glutamatergic neurotransmission has been implicated in mechanisms of
      alcohol-induced neurodegeneration and cognitive impairment, but the underlying
      mechanism remains unknown. Here, we examined whether the group II metabotropic
      glutamate receptor agonist LY379268 prevents neuronal death and learning deficits
      in a rat model of binge-like exposure to alcohol. METHODS: Following 4-day binge
      alcohol exposure concurrent with LY379268 or vehicle treatment, Fluoro-Jade B and
      transforming growth factor-beta (TGF-beta) staining were carried out, and
      reversal learning in the Morris water maze was assessed. RESULTS: Fluoro-Jade B
      staining indicating neurodegeneration was most extensive in the ventral
      hippocampus and the entorhinal cortex (EC). LY379268 was potently neuroprotective
      in the EC but not in the dentate gyrus of the hippocampus. In parallel, binge
      alcohol exposure suppressed TGF-beta expression in both the EC and dentate gyrus,
      whereas LY379268 increased TGF-beta in the EC only. Finally, neuroprotective
      effects of LY379268 were accompanied by prevention of deficits in spatial
      reversal learning. CONCLUSIONS: Our data support a neuroprotective role for group
      II metabotropic glutamate receptor agonists and TGF-beta in alcohol-induced
      neurodegeneration.

PMID- 20132927
TI  - Acute negative affect relief from smoking depends on the affect situation and
      measure but not on nicotine.
AB  - BACKGROUND: Smoking acutely relieves negative affect (NA) due to smoking
      abstinence but may not relieve NA from other sources, such as stressors. METHODS:
      Dependent smokers (n = 104) randomly assigned to one of three smoking conditions
      (nicotine or denicotinized cigarettes, or no smoking) completed four negative
      mood induction procedures (one per session): 1) overnight smoking abstinence, 2)
      challenging computer task, 3) public speech preparation, and 4) watching negative
      mood slides. A fifth session involved a neutral mood control. The two smoking
      groups took four puffs on their assigned cigarette and then smoked those same
      cigarettes ad libitum during continued mood induction. All subjects rated their
      level of NA and positive affect on several measures (Mood Form, Positive and
      Negative Affect Scale, Stress-Arousal Checklist, and State-Trait Anxiety
      Inventory-state). They also rated craving and withdrawal. RESULTS: Negative
      affect relief from smoking depended on the NA source (i.e., mood induction
      procedure) and the affect measure. Smoking robustly relieved NA due to abstinence
      on all four measures but only modestly relieved NA due to the other sources and
      typically on only some measures. Smoking's effects on positive affect and
      withdrawal were similar to effects on NA, but relief of craving depended less on
      NA source. Smoking reinforcement only partly matched the pattern of NA relief.
      Few responses differed between the nicotine and denicotinized smoking groups.
      CONCLUSIONS: Acute NA relief from smoking depends on the situation and the affect
      measure used but may not depend on nicotine intake. These results challenge the
      common assumption that smoking, and nicotine in particular, broadly alleviates
      NA.

PMID- 20132928
TI  - Primate early life stress leads to long-term mild hippocampal decreases in
      corticosteroid receptor expression.
AB  - BACKGROUND: Expression of mineralocorticoid receptor (MR) and glucocorticoid
      receptor (GR) genes are moderately reduced in several brain regions in
      depression. These reductions could be partly due to early life stress (ELS),
      which predicts emotional disorders. Controlled primate studies are important to
      test whether ELS sufficient to induce long-term emotional changes also induces
      long-term altered MR and/or GR brain expression. METHODS: In the common marmoset,
      ELS of daily 30-120-min social isolation across month-1 resulted in some long
      term changes in homeostasis and emotional behavior. In some of these same
      subjects, the aim of this study was to use marmoset-specific riboprobes to
      determine whether ELS produced long-term effects on brain MR and GR gene
      expression. RESULTS: At adolescence, relative to control subjects, ELS marmosets
      exhibited mildly reduced messenger RNA signal for both MR (-15%, p = .05) and GR
      (-13%, p = .02) in hippocampus-primarily CA1-2-but not in prefrontal cortex,
      other cortical regions, or hypothalamus. CONCLUSIONS: In adolescent marmoset
      monkey brains, reduced hippocampal expression of MR and GR are consistent chronic
      indicators of ELS. It is unlikely that these chronic, mild, specific reductions
      were acute-mediators of the observed long-term emotional effects of ELS. However,
      they do suggest involvement of hippocampal MR/GR in the neurodevelopmental
      effects of ELS.

PMID- 20132929
TI  - Action of modafinil--increased motivation via the dopamine transporter inhibition
      and D1 receptors?
AB  - BACKGROUND: Modafinil is prescribed for the treatment of narcolepsy. It has been
      postulated that modafinil might treat cognitive disruption in neuropsychiatric
      disorders. The mechanisms underlying such modafinil-induced improvements in
      performance have yet to be delineated however. Recent evidence suggests that
      modafinil might block the dopamine transporter (DAT) and that the dopamine D1
      receptor (D1R) might contribute to modafinil effects. METHODS: Dopamine D1R
      wildtype (WT), heterozygous (HT), and knockout (KO) mice received vehicle,
      modafinil, or the selective DAT blocker GBR12909 in a progressive ratio
      breakpoint study. RESULTS: Both modafinil and GBR12909 increased motivation in
      the task as measured by an increase in breakpoint in WT and HT mice. These drug
      induced increases in motivation were reduced in dopamine D1R HT mice relative to
      their WT littermates. The D1R KO mice did not respond in the task. CONCLUSIONS:
      These data support the hypothesis that modafinil increases motivation. Moreover,
      given the similarity of effects with GBR12909, the data corroborate evidence that
      the behavioral effects of modafinil might be due to DAT inhibition. Furthermore,
      the dopamine D1R might play a downstream role in mediating modafinil-induced
      increases in motivation. Thus, studies reporting cognition-enhancing effects of
      modafinil might have been influenced by its ability to increase motivation.

PMID- 20132930
TI  - Automatic recognition of midline shift on brain CT images.
AB  - Midline shift is one of the most important quantitative features clinicians use
      to evaluate the severity of brain compression by various pathologies. It can be
      recognized by modeling brain deformation according to the estimated biomechanical
      properties of the brain and the cerebrospinal fluid spaces. This paper proposes a
      novel method to identify the deformed midline according to the above hypothesis.
      In this model, the deformed midline is decomposed into three segments: the upper
      and the lower straight segments representing parts of the tough dura mater
      separating two brain hemispheres, and the central curved segment formed by a
      quadratic Bezier curve, representing the intervening soft brain tissue. The
      deformed midline is obtained by minimizing the summed square of the differences
      across all midline pixels, to simulate maximal bilateral symmetry. A genetic
      algorithm is applied to derive the optimal values of the control points of the
      Bezier curve. Our algorithm was evaluated on pathological images from 81
      consecutive patients treated in a single institute over a period of one year. Our
      algorithm is able to recognize the deformed midlines in 65 (80%) of the patients
      with an accuracy of 95%, making it a useful tool for clinical decision-making.

PMID- 20132931
TI  - The cognitive neuroscience of aging: New findings on compensation and
      connectivity.

PMID- 20132932
TI  - Improved quality of life is partly explained by fewer symptoms after treatment of
      fibroids with mifepristone.
AB  - OBJECTIVE: To examine mediators of mifepristone treatment on improvements in
      health-related quality of life (HRQOL) among women with symptomatic fibroids.
      METHODS: The study sample included women with symptomatic uterine fibroids who
      were treated with 5mg or 2.5mg of mifepristone or placebo. Assessments of uterine
      size (ultrasound), pain (McGill pain questionnaire), bleeding (diary), anemia
      (gm/dL), and HRQOL measured using the uterine fibroid symptom quality of life
      scale were done at baseline, 3 months, and 6 months. The improvements in HRQOL
      that could be explained by changes in these clinical factors were assessed.
      RESULTS: The final sample included 62 women. Treatment with mifepristone was
      associated with significant improvement in HRQOL, which was explained in part by
      reduction in pain (28%, P<0.001) and bleeding (18%, P<0.001). Reduction in
      uterine volume was of marginal significance (P=0.05) and was associated with a
      decrease in HRQOL (7%). Much of the impact of treatment on HRQOL (61%) remained
      unexplained in this model. CONCLUSIONS: Improvements in HRQOL after treatment
      with mifepristone are partly explained by improvements in pain and bleeding, but
      not uterine size. However, most of the improvement in HRQOL is not explained by
      improvements in these clinical parameters.

PMID- 20132933
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on bone material
      properties.
AB  - Dioxins are known to decrease bone strength, architecture and density. However,
      their detailed effects on bone material properties are unknown. Here we used
      nanoindentation methods to characterize the effects of 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) on nanomechanical behaviour of bone matrix. Pregnant rats were
      treated with a single intragastric dose of TCDD (1 microg/kg) or vehicle on
      gestational day 11. Tibias of female offspring were sampled on postnatal day
      (PND) 35 or 70, scanned at mid-diaphysis with pQCT, and evaluated by three-point
      bending and nanoindentation. TCDD treatment decreased bone mineralization
      (p<0.05), tibial length (p<0.01), cross-sectional geometry (p<0.05) and bending
      strength (p<0.05). Controls showed normal maturation pattern between PND 35 and
      70 with decreased plasticity by 5.3% and increased dynamic hardness, storage and
      complex moduli by 26%, 13% and 12% respectively (p<0.05), while similar
      maturation was not observed in TCDD-exposed pups. In conclusion, for the first
      time, we demonstrate retardation of bone matrix maturation process in TCDD
      exposed animals. In addition, the study confirms that developmental TCDD exposure
      has adverse effects on bone size, strength and mineralization. The current
      results in conjunction with macromechanical behaviour suggest that reduced bone
      strength caused by TCDD is more associated with the mineralization and altered
      geometry of bones than with changes at the bone matrix level.

PMID- 20132934
TI  - Application of copper sulfate pentahydrate as an ammonia removal reagent for the
      determination of trace impurities in ammonia by gas chromatography.
AB  - Rapid analysis of trace permanent gas impurities in high purity ammonia gas for
      the microelectronics industry is described, using a gas chromatograph equipped
      with a phtoionization detector. Our system incorporates a reactive precolumn in
      combination with the analytical column to remove the ammonia matrix peak that
      otherwise would complicate the measurements due to baseline fluctuations and loss
      of analytes. The performance of 21 precolumn candidate materials was evaluated.
      Copper sulfate pentahydrate (CuSO(4).5H(2)O) was shown to selectively react with
      ammonia at room temperature and atmospheric column pressures, without affecting
      the hydrogen, oxygen, nitrogen, methane or carbon monoxide peak areas. To prevent
      loss of trace carbon dioxide, an additional boron trioxide reactant layer was
      inserted above the copper sulfate pentahydrate bed in the reactive precolumn.
      Using the combined materials, calibration curves for carbon dioxide proved to be
      equivalent in both ammonia and helium matrix gases. These curves were equivalent
      in both matrix gases. The quantitative performance of the system was also
      evaluated. Peak repeatabilities, based on eight injections, were in the range of
      4.1-8.2% relative standard deviation; and detection limits were 6.9 ppb for H(2),
      1.8 ppb for O(2), 1.6 ppb for N(2), 6.4 ppb for CH(4), 13 ppb for CO, and 5.4 ppb
      for CO(2).

PMID- 20132935
TI  - Design and implementation of an array of micro-electrochemical detectors for two
      dimensional liquid chromatography--proof of principle.
AB  - Simultaneous two-dimensional liquid chromatography (2D-LC) is an implementation
      of two-dimensional liquid chromatography which has the potential to provide very
      fast, yet highly efficient separations. It is based on the use of time x space
      and space x space separation systems. The basic principle of this instrument has
      been validated long ago by the success of two-dimensional thin layer
      chromatography. The construction of a pressurized wide and flat column (100 mm x
      100 mm x 1 mm) operated under an inlet pressure of up to 50 bar was described
      previously. However, to become a modern analytical method, simultaneous 2D-LC
      requires the development of detectors suitable for the monitoring of the
      composition of the eluent of this pressurized planar, wide column. An array of
      five equidistant micro-electrochemical sensors was built for this purpose and
      tested. Each sensor is a three-electrode system, with the working electrode being
      a 25 microm polished platinum micro-electrode. The auxiliary electrode is a thin
      platinum wire and the reference electrode an Ag/AgCl (3M sat. KCl) electrode. In
      this first implementation, proof of principle is demonstrated, but the final
      instrument will require a much larger array.

PMID- 20132936
TI  - Synthesis and application of hypercrosslinked polymers with weak cation-exchange
      character for the selective extraction of basic pharmaceuticals from complex
      environmental water samples.
AB  - The synthesis of high specific surface area sorbents (HXLPP-WCX) in the form of
      hypercrosslinked polymer microspheres with narrow particle size distributions,
      average particle diameters around 6 microm, and weak cation-exchange (WCX)
      character, is described. The WCX character arises from carboxylic acid moieties
      in the polymers, derived from the comonomer methacrylic acid. A novel HXLPP-WCX
      sorbent with an attractive set of chemical and physical properties was then used
      in an off-line solid-phase extraction (SPE) protocol for the selective extraction
      of a group of basic compounds from complex environmental samples, a priority
      being the clean separation of the basic compounds of interest from acidic
      compounds and interferences. The separation power of the new sorbent for basic
      pharmaceuticals was compared to two commercially available, mixed-mode sorbents,
      namely Oasis WCX and Strata-X-CW. Under identical experimental conditions, HXLPP
      WCX was found to deliver both higher capacity and better selectivity in SPE than
      either of the two commercially available materials. In an optimised SPE protocol,
      the HXLPP-WCX sorbent gave rise to quantitative and selective extractions of low
      microg l(-1) levels of basic pharmaceuticals present in 500 ml of river water and
      250 ml of effluent waste water.

PMID- 20132937
TI  - Analysis of amphetamine and methamphetamine as emerging pollutants in wastewater
      and wastewater-impacted streams.
AB  - The identification and quantitation of the non-ecstasy amphetamine-type
      stimulants (ATSs) amphetamine and methamphetamine in lakes, rivers, wastewater
      treatment plant influents, effluents, and biosolids are reviewed. Neither
      monitoring nor reporting is required of these ATSs, which are considered emerging
      pollutants, but they have been identified in the environment. Amphetamine and
      methamphetamine enter our water supply by human excretion after legal or illegal
      consumption and via manufacturing in clandestine laboratories. Analytical
      methodology for sampling, sample preparation, separation, and detection of ATSs
      is discussed. Reported occurrences of ATSs in the environment and their use in
      municipal sewage epidemiology are noted. Future research needs that challenge
      applications of analytical techniques are discussed. The review focuses on
      research reported from 2004 to 2009.

PMID- 20132938
TI  - Evaluation of the enantioseparation capability of the novel chiral selector
      clindamycin phosphate towards basic drugs by micellar electrokinetic
      chromatography.
AB  - To date, a series of chiral selectors have been utilized successfully in
      capillary electrophoresis (CE). Among these various chiral selectors, macrocyclic
      antibiotics have been demonstrated to represent powerful enantioselectivity
      towards many chiral compounds. Differing from macrocyclic antibiotics, the use of
      lincosamide antibiotics as chiral selectors has not been reported previously. In
      our recent work, clindamycin phosphate belonging to the group of lincosamides has
      been first used as a chiral selector in capillary zone electrophoresis (CZE). In
      this paper, a micellar electrokinetic chromatography (MEKC) method has been
      developed for the evaluation of enantioseparation capability of this novel chiral
      selector towards several racemic basic drugs. As observed during the course of
      this work, clindamycin phosphate allowed excellent separation of the enantiomers
      of nefopam, citalopram, tryptophan, chlorphenamine, propranolol and metoprolol,
      as well as partial enantioresolution of tryptophan methyl ester and cetirizine.
      In this MEKC chiral separation system, different types of anionic surfactants,
      organic additives and background electrolytes were tested, and satisfactory
      enantioseparations of basic drugs above-mentioned were achieved using sodium
      dodecyl sulfate (SDS) as the surfactant, isopropanol as the organic additive, and
      phosphate as the background electrolyte. Furthermore, both migration times and
      enantioseparation of the analytes were influenced by several experimental
      parameters such as pH of the BGE, clindamycin phosphate and SDS concentrations,
      phosphate and isopropanol concentrations, and applied voltage. Consequently, the
      effects of these factors on enantioseparations of the studied basic drugs were
      systematically investigated in order to evaluate the stereoselectivity of
      clindamycin phosphate in MEKC.

PMID- 20132939
TI  - Peak half-width plots to study the effect of organic solvents on the peak
      performance of basic drugs in micellar liquid chromatography.
AB  - The addition of the anionic surfactant sodium dodecyl sulphate (SDS) to hydro
      organic mixtures of methanol, ethanol, propanol or acetonitrile with water
      yielded enhanced peak shape (i.e. increased efficiencies and symmetrical peaks)
      for a group of basic drugs (beta-blockers) chromatographed with a Kromasil C18
      column. The effect can be explained by the thin layer of surfactant associated to
      the hydrocarbon chain on the stationary phase in the presence of the organic
      solvents, which covers the free silanols on the siliceous support avoiding their
      interaction with the cationic basic drugs. These instead interact with the
      anionic head of the surfactant increasing their retention and allowing a more
      facile mass transfer. The peak shape behaviour with the four organic solvents
      (methanol, ethanol, propanol and acetonitrile) was checked in the presence and
      absence of SDS. The changes in peak broadening rate and symmetry inside the
      chromatographic column were assessed through the construction of peak half-width
      plots (linear relationships between the left and right half-widths at 10% peak
      height versus the retention time). The examination of the behaviour for a wide
      range of compositions indicated that the effect of acetonitrile in the presence
      of SDS is different from ethanol and propanol, which behave similarly.
      Acetonitrile seems to be superior to the alcohols in terms of peak shape, which
      can be interpreted by the larger reduction in the adsorbed surfactant layer on
      the C18 column. However, the decreased efficiencies observed at increasing
      surfactant concentration in the mobile phase should be explained by the reduction
      in retention times, more than by a change in the stationary phase nature.

PMID- 20132940
TI  - A high throughput metabolic stability screening workflow with automated
      assessment of data quality in pharmaceutical industry.
AB  - One of the most commonly performed in vitro ADME assays during the lead
      generation and lead optimization stage of drug discovery is metabolic stability
      evaluation. Metabolic stability is typically assessed in liver microsomes, which
      contain Phase I metabolizing enzymes, mainly cytochrome P450 enzymes (CYPs). The
      amount of parent drug metabolized by these CYPs is determined by LC/MS/MS. The
      metabolic stability data are typically used to rank order compounds for in vivo
      evaluation. We describe a streamlined and intelligent workflow for the metabolic
      stability assay that permits high throughput analyses to be carried out while
      maintaining the standard of high quality. This is accomplished in the following
      ways: a novel post-incubation pooling strategy based on cLogD(3.0) values,
      coupled with ultra-performance liquid chromatography/tandem mass spectrometry
      (UPLC/MS/MS), enables sample analysis times to be reduced significantly while
      ensuring adequate chromatographic separation of compounds within a group, so as
      to reduce the likelihood of compound interference. Assay quality and fast
      turnaround of data reports is ensured by performing automated real-time
      intelligent re-analysis of discrete samples for compounds that do not pass user
      definable criteria during the pooling analysis. Intelligent, user-independent
      data acquisition and data evaluation are accomplished via a custom visual basic
      program that ties together every step in the workflow, including cassette
      compound selection, compound incubation, compound optimization, sample analysis
      and re-analysis (when appropriate), data processing, data quality evaluation, and
      database upload. The workflow greatly reduces labor and improves data turnaround
      time while maintaining high data quality.

PMID- 20132941
TI  - Poly(ethylenimine)-stabilized silver nanoparticles assembled into 2-dimensional
      arrays at water-toluene interface.
AB  - A one-pot, size-controlled preparation of amine-functionalized silver
      nanoparticles is possible using poly(ethylenimine) (PEI) as a reducing and a
      stabilizing agent simultaneously. The PEI-stabilized Ag nanoparticles thus
      prepared in aqueous phase can further be assembled into 2-dimensional (2-D)
      arrays at the water-toluene interface by heating. By the addition of benzenethiol
      (BT) into the toluene, a more robust 2-D film is formed, not only at the
      interface but also on the inner surface of the sampling bottle. The latter Ag
      film can also be formed, through brief contact with the mixture, on glass slides
      and even on dielectric beads and cotton fabrics. These Ag-coated films are highly
      surface-enhanced Raman scattering (SERS) active and also exhibit a very intense
      SERS spectrum of 4-aminobenzenethiol (4-ABT) or 4-nitrobenzenethiol (4-NBT) via a
      place-exchange reaction that takes place between BT and 4-ABT or 4-NBT. In
      addition, the Ag-coated fabrics would be used as antibacterial gauzes for the
      treatment of burned skin and also as antistatic mats for the ready dissipation of
      electrical energy buildup. The present electroless deposition method of Ag is
      thus expected to serve as a technique in high demand in various fields.

PMID- 20132942
TI  - Three-dimensional off-lattice Monte Carlo simulations on a direct relation
      between experimental process parameters and fractal dimension of colloidal
      aggregates.
AB  - It has been a big challenge to explore a direct relation of experimental
      parameters such as pH, electrolyte concentration, particle size, and temperature
      with the final structures of aggregates, because Monte Carlo simulations have
      been performed on the basis of arbitrarily chosen sticking probability. We
      attempted to incorporate colloidal theory to Monte Carlo simulations for two
      model systems of CuO- and SiO(2)-water systems, so as to resolve this difficulty.
      Conducting three-dimensional off-lattice MC simulations at various pHs for both
      systems, we investigated effects of pH on fractal structures of aggregates,
      encompassing the whole aggregation regime from diffusion-limited cluster-cluster
      aggregation to reaction-limited cluster-cluster aggregation. Moreover, developing
      a functional analysis, we found an explicit correlation between experimental
      parameters, sticking probability, and the fractal dimension of aggregates for
      both systems.

PMID- 20132943
TI  - A comparison between physically and chemically driven etching in the oxidation of
      graphite surfaces.
AB  - The etching of graphite surfaces by two different types of oxidative treatments,
      namely dielectric barrier discharge (DBD) air plasma and ultraviolet-generated
      ozone (UVO), has been investigated and compared by means of scanning tunneling
      microscopy (STM), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS).
      Although the attack is initiated in both cases with the formation of individual,
      isolated atomic-scale defects (in particular, atomic vacancies), its subsequent
      evolution indicated that different mechanisms drive the surface modification in
      the two types of treatment, which greatly differ in etching selectivity. Thus,
      physical processes (i.e., ion bombardment) dominate the attack by DBD air plasma,
      which are not present in the case of UVO oxidation. The effects of the different
      etching mechanisms on the graphite surface structure, as visualized by STM down
      to the atomic scale, are discussed and found to be consistent with the Raman
      spectroscopy and XPS data. This type of information can be relevant when
      selecting the most appropriate type of surface modification of carbon materials
      for specific purposes.

PMID- 20132944
TI  - Investigations on the photoinduced interaction of water soluble thioglycolic acid
      (TGA) capped CdTe quantum dots with certain porphyrins.
AB  - The photoinduced interaction of TGA capped CdTe quantum dots (QDs) with
      porphyrins such as meso-tetrakis(4-sulfonatophenyl)porphyrin [TSPP], meso
      tetrakis(4-carboxyphenyl)porphyrin [TCPP], meso-tetrakis (4-N
      methylpyridyl)porphyrin [TMPyP] and meso-tetraphenylporphyrin [TPP] has been
      studied by using absorption, steady state and time resolved fluorescence
      spectroscopy. The QD surface was negatively charged due to thiol capping agent
      containing carboxylic group. Positively charged TMPyP interacts with QDs through
      charge transfer mechanism, negatively charged porphyrins (TCPP and TSPP)
      interacted through energy transfer mechanism and the neutral one (TPP) does not
      have any interaction. The Stern-Volmer constant, quenching rate constant,
      association constants, rate of electron transfer and energy transfer parameters
      were calculated from the fluorescence data. Effect of molecular structure has
      also been studied.

PMID- 20132945
TI  - Self-assembling systems: mining a rich vein.
AB  - This paper summarizes a few of the self-assembling systems investigated in the
      authors' laboratory over the years. These include systems that mimic an enzyme,
      solubilize drugs, release encapsulated guests, assemble via hydrophobic surfaces,
      exhibit hysteresis in films, link cancer cells to vesicles, and destroy toxic
      compounds. Although the amphiphilic molecules are all rather different, one
      overriding theme predominates: just as the properties of molecules are not simple
      extrapolations from atoms, properties of self-assemblies are not simple
      extrapolations from molecules. Groups of molecules, properly assembled, can
      accomplish much more than an equal number of molecules functioning separately.

PMID- 20132946
TI  - Removal and recovery of Chrysoidine Y from aqueous solutions by waste materials.
AB  - This article describes the use of bottom ash [a power plant waste] and de-oiled
      soya [an agricultural waste] as effective adsorbents for the removal of a
      hazardous azo dye [Chrysoidine Y] from its aqueous solutions. This paper presents
      an experimental study and discussion of the adsorption characteristics of this
      dye on the two adsorbents. The adsorbents have been characterized, and also the
      effects of time, temperature, concentration, pH, and sieve size on the extent of
      adsorption have been evaluated. Batch adsorption measurements, kinetic studies,
      and column operations have been performed to elucidate the dye uptake capacity of
      the adsorbents. The monolayer adsorption capacities at 30 degrees C have been
      found from Langmuir analysis to be 7.27x10(-5) mol g(-1) and 3.35x10(-5) mol g(
      1) for bottom ash and de-oiled soya, respectively. Adsorption kinetics
      experimental data are indicative of pseudo-second order kinetics during these
      processes. Column experiments indicate practical utility of the adsorbents for
      eradicating hazardous dyes from effluents. The recovery of the adsorbed dye from
      bottom ash and de-oiled soya, have been found to be 85% and 99%, respectively.

PMID- 20132947
TI  - Restricted meniscus convective self-assembly.
AB  - Convective (or evaporation-induced) self-assembly is a standard technique for
      depositing uniform, poly-crystalline coatings of nanospheres across multiple
      square centimeters on the timescale of minutes. In this paper, we present a
      variation of this technique, where the drying meniscus is restricted by a
      straight-edge located approximately 100 microm above the substrate adjacent to
      the drying zone. Surprisingly, we find this technique to yield films at roughly
      twice the growth rate compared to the standard technique. We attribute this to
      differing rates of diffusion of vapor from the drying crystal in the two cases.
      We also investigate the crystal growth rate dependence on ambient relative
      humidity and find, contrary to some previous reports, that the growth rate
      depends strongly on the humidity. We introduce a model which indicates that while
      the length of the drying zone may increase with humidity, this alone cannot
      compensate for the simultaneous reduction in evaporation rate, so a lower
      humidity must always lead to a higher growth speed. Comparing the model to our
      experimental results, we find that the length of the drying zone is constant and
      mostly independent of parameters such as humidity and surface tension.

PMID- 20132948
TI  - Thermodynamic analysis of the wetting behavior of dual scale patterned
      hydrophobic surfaces.
AB  - Nature-made superhydrophobic surfaces, such as lotus leaves, have a dual scale
      roughness (in micro and nanoscales) which is the main reason for their unique
      wettability. While there are a lot of experimental studies on wettability of
      hierarchical roughness, there is a lack of a thorough analysis of the
      contribution of micro and nanoscale roughness on wettability behavior despite
      interesting features these surfaces have. In this paper, a thermodynamic approach
      has been used to predict the wetting behavior of water droplet on a dual scale
      roughness. The predictions made by the model are compared with experimental
      results reported in the literature. The thermodynamic analysis has also been used
      to provide an insight into the origin of the special hydrophobicity of surfaces
      with dual scale roughness. It was found that there is an interaction between
      micro and nanoscale roughness on wettability of each other which results in a
      synergy among the components of roughness in enhancing hydrophobicity. All
      possible wetting states of a surface with dual scale roughness were presented in
      a wetting map. The contact angle for each state was also calculated to determine
      the maximum water repellency condition.

PMID- 20132949
TI  - Risk factor analysis for postoperative acute respiratory distress syndrome and
      early mortality after pneumonectomy: the predictive value of preoperative lung
      perfusion distribution.
AB  - OBJECTIVES: This study aims to establish the preoperative risk factors in the
      development of acute respiratory distress syndrome (ARDS) and early mortality
      after pneumonectomy for lung cancer and to examine the influence of reduced
      pulmonary perfusion on outcomes. METHODS: Between 1994 and 2009, of 425 patients
      who underwent simple pneumonectomy for primary lung cancer, 164 who were
      preoperatively evaluated with lung perfusion scanning formed the population of
      this study. RESULTS: Of 30 (18.3%) patients who had major pulmonary
      complications, 17 (10.4%) progressed to ARDS, 15 of whom subsequently died. On
      multivariable logistic regression analyses, lower predicted postoperative forced
      expiratory volume in 1 second (ppo-FEV(1); relative risk of 0.93 [P = .020] for
      ARDS and 0.94 [P = .027] for mortality) and greater perfusion fraction of
      resected lung (relative risk of 1.10 [P = .003] for ARDS and 1.09 [P = .002] for
      mortality) were found to be independent factors associated with ARDS and early
      mortality. With a cut-off value of 35% for perfusion fraction of resected lung,
      patients with a perfusion fraction of greater than 35% had a greater incidence of
      ARDS (17.3% vs 3.3%, P = .005) and early mortality (19.8% vs 6.0%, P = .010) than
      those with a perfusion fraction of 35% or less. CONCLUSIONS: Patients with a low
      ppo-FEV(1), a high perfusion fraction of resected lung, or both had a higher
      incidence of ARDS and early mortality after pneumonectomy. Therefore, although
      the ppo-FEV(1) appears to be within an acceptable limit for pneumonectomy, much
      attention should be given to patients with a high perfusion fraction of resected
      lung.

PMID- 20132950
TI  - Right ventricular failure in patients with the HeartMate II continuous-flow left
      ventricular assist device: incidence, risk factors, and effect on outcomes.
AB  - OBJECTIVE: The aim of this study was to evaluate the incidence, risk factors, and
      effect on outcomes of right ventricular failure in a large population of patients
      implanted with continuous-flow left ventricular assist devices. METHODS: Patients
      (n = 484) enrolled in the HeartMate II left ventricular assist device (Thoratec,
      Pleasanton, Calif) bridge-to-transplantation clinical trial were examined for the
      occurrence of right ventricular failure. Right ventricular failure was defined as
      requiring a right ventricular assist device, 14 or more days of inotropic support
      after implantation, and/or inotropic support starting more than 14 days after
      implantation. Demographics, along with clinical, laboratory, and hemodynamic
      data, were compared between patients with and without right ventricular failure,
      and risk factors were identified. RESULTS: Overall, 30 (6%) patients receiving
      left ventricular assist devices required a right ventricular assist device, 35
      (7%) required extended inotropes, and 33 (7%) required late inotropes. A
      significantly greater percentage of patients without right ventricular failure
      survived to transplantation, recovery, or ongoing device support at 180 days
      compared with patients with right ventricular failure (89% vs 71%, P < .001).
      Multivariate analysis revealed that a central venous pressure/pulmonary capillary
      wedge pressure ratio of greater than 0.63 (odds ratio, 2.3; 95% confidence
      interval, 1.2-4.3; P = .009), need for preoperative ventilator support (odds
      ratio, 5.5; 95% confidence interval, 2.3-13.2; P < .001), and blood urea nitrogen
      level of greater than 39 mg/dL (odds ratio, 2.1; 95% confidence interval, 1.1
      4.1; P = .02) were independent predictors of right ventricular failure after left
      ventricular assist device implantation. CONCLUSIONS: The incidence of right
      ventricular failure in patients with a HeartMate II ventricular assist device is
      comparable or less than that of patients with pulsatile-flow devices. Its
      occurrence is associated with worse outcomes than seen in patients without right
      ventricular failure. Patients at risk for right ventricular failure might benefit
      from preoperative optimization of right heart function or planned biventricular
      support.

PMID- 20132951
TI  - Normokalemic adenosine-lidocaine cardioplegia: importance of maintaining a
      polarized myocardium for optimal arrest and reanimation.
AB  - OBJECTIVE: Depolarizing potassium cardioplegia does not afford optimal
      cardioprotection in pediatric or adult patients requiring complicated operative
      procedures. Polarizing adenosine-lidocaine cardioplegia has been shown to be
      cardioprotective without hyperkalemia. Our aim was to examine the effects of
      changing extracellular potassium levels in adenosine-lidocaine cardioplegia on
      arrest and reanimation properties. METHODS: Isolated-perfused rat hearts (n = 96)
      were arrested at 32 degrees C to 33 degrees C for 1 or 2 hours with intermittent
      200 mumol/L adenosine and 500 mumol/L lidocaine in modified Krebs-Henseleit
      buffer with 0.1, 3.0, 5.9, 10, and 16 mmol/L potassium or with 16 or 25 mmol/L
      potassium in Krebs-Henseleit buffer (n = 8 for each group). Membrane potentials
      were estimated in the arrested ventricular myocardium (n = 42), and recovery
      function was measured in working mode during 60 minutes' reperfusion. RESULTS:
      Arrest was interrupted by breakout beats in the adenosine-lidocaine hypokalemic
      (0.1 and 3 mmol/L potassium) and non-adenosine-lidocaine hyperkalemic (16 and 25
      mmol/L potassium) groups. The membrane potentials for the non-adenosine-lidocaine
      16 and 25 mmol/L potassium groups were -51 and -39 mV, and those for the
      adenosine-lidocaine groups (0.1, 3.0, 5.9, 10, and 16 mmol/L potassium) were 
      183, -94, -75, -65, and -49 mV, respectively. After 1 hour of arrest, coronary
      vascular resistance increased linearly in adenosine-lidocaine cardioplegia with
      increasing potassium levels (5.9, 10, and 16 mmol/L), and the slope increased
      more than 2-fold after 2 hours. Nearly 40% of hearts in the adenosine-lidocaine
      (0.1 mmol/L potassium) and non-adenosine-lidocaine 25 mmol/L potassium groups
      failed to recover after 1 hour arrest. After 2 hours, hearts in the polarizing
      (5.9 mmol/L potassium) adenosine-lidocaine group increased coronary vascular
      resistance by only 30% and spontaneously recovered 107% heart rate, 92% systolic
      pressure, 81% aortic flow, and 113% coronary flow (all metrics returned 85% to
      100% at 15 minutes) with no reperfusion arrhythmias. In contrast, hearts in the
      adenosine-lidocaine (3, 10, and 16 mmol/L potassium) groups were all slow to
      recover (15% to 40% return at 15 minutes) and experienced arrhythmias. Increasing
      potassium levels in adenosine-lidocaine cardioplegia from 5.9 to 16 mmol/L
      resulted in a 67% loss of left ventricular contractility. CONCLUSIONS: Polarizing
      adenosine-lidocaine cardioplegia (5.9 mmol/L potassium) administered
      intermittently at 33 degrees C provides superior arrest and reanimation profiles
      under normokalemic conditions when the myocardial cell membrane potential is
      close to its resting state.

PMID- 20132952
TI  - PCB exposure in sea otters and harlequin ducks in relation to history of
      contamination by the Exxon Valdez oil spill.
AB  - Exposure to contaminants other than petroleum hydrocarbons could confound
      interpretation of Exxon Valdez oil spill effects on biota at Prince William
      Sound, Alaska. Hence, we investigated polychlorinated biphenyls (PCBs) in blood
      of sea otters and harlequin ducks sampled during 1998. PCB concentrations
      characterized by lower chlorinated congeners were highest in sea otters from the
      unoiled area, whereas concentrations were similar among harlequin ducks from the
      oiled and unoiled area. Blood enzymes often elevated by xenobiotics were not
      related to PCB concentrations in sea otters. Only sea otters from the unoiled
      area had estimated risk from PCBs, and PCB composition or concentrations did not
      correspond to reported lower measures of population performance in sea otters or
      harlequin ducks from the oiled area. PCBs probably did not influence limited sea
      otter or harlequin duck recovery in the oiled area a decade after the spill.

PMID- 20132953
TI  - Flavone synthase II (CYP93B16) from soybean (Glycine max L.).
AB  - Flavonoids are a very diverse group of plant secondary metabolites with a wide
      array of activities in plants, as well as in nutrition and health. All flavonoids
      are derived from a limited number of flavanone intermediates, which serve as
      substrates for a variety of enzyme activities, enabling the generation of
      diversity in flavonoid structures. Flavonoids can be characteristic metabolites,
      like isoflavonoids for legumes. Others, like flavones, occur in nearly all
      plants. Interestingly, there exist two fundamentally different enzymatic systems
      able to directly generate flavones from flavanones, flavone synthase (FNS) I and
      II. We describe an inducible flavone synthase activity from soybean (Glycine max)
      cell cultures, generating 7,4'-dihydroxyflavone (DHF), which we classified as FNS
      II. The corresponding full-length cDNA (CYP93B16) was isolated using known FNS II
      sequences from other plants. Functional expression in yeast allowed the detailed
      biochemical characterization of the catalytic activity of FNS II. A direct
      conversion of flavanones such as liquiritigenin, naringenin, and eriodictyol into
      the corresponding flavones DHF, apigenin and luteolin, respectively, was
      demonstrated. The enzymatic reaction of FNSII was stereoselective, favouring the
      (S)- over the (R)-enantiomer. Phylogenetic analyses of the subfamily of plant
      CYP93B enzymes indicate the evolution of a gene encoding a flavone synthase which
      originally catalyzed the direct conversion of flavanones into flavones, via early
      gene duplication into a less efficient enzyme with an altered catalytic
      mechanism. Ultimately, this allowed the evolution of the legume-specific
      isoflavonoid synthase activity.

PMID- 20132954
TI  - The protective effect of a Toxoplasma gondii SAG1 plasmid DNA vaccine in mice is
      enhanced with IL-18.
AB  - More effective vaccines against Toxoplasma gondii may contribute to the control
      of this pathogen that has major veterinary and public health significance. In
      this study, two recombinant plasmids pcDNA/TgSAG1 and pVAX/mIL-18 containing T.
      gondii SAG1 (TgSAG1) and murine cytokine interleukin-18 (IL-18) were evaluated
      for their ability to protect mice against T. gondii challenge. Mice were given
      two intramuscular immunizations 3 weeks apart, and challenged with T. gondii 3
      weeks later. All animals vaccinated with pcDNA/TgSAG1 alone or with pVAX/mIL-18
      developed specific anti-TLA (T. gondii lysate antigen) antibodies and specific
      lymphocyte proliferative responses. Co-injection of pVAX/mIL-18 significantly
      increased the production of IFN-gamma and IL-2. Further, challenge experiments
      showed that co-immunization with pVAX/mIL-18 significantly (P<0.05) increased the
      survival rate (60%), compared with pcDNA/TgSAG1 alone (40%). Therefore,
      codelivery of the IL-18-secreting plasmid potentiates the induction and
      maintenance of the type 1 helper T-cell immune response and may be a potent
      strategy for enhancing the protective efficacy of vaccines against T. gondii.

PMID- 20132955
TI  - Hyperglycaemia but not hyperlipidaemia decreases serum amylase and increases
      neutrophils in the exocrine pancreas of cats.
AB  - The goal of the study was to determine whether hyperglycaemia or hyperlipidaemia
      causes pancreatitis in cats and to assess the effect of excess serum glucose and
      lipids on amylase and lipase activity. Ten-day hyperglycaemic and hyperlipidaemic
      clamps were carried out in five and six healthy cats, respectively. Ten healthy
      cats received saline and served as controls. The activity of amylase was below
      the normal range in 4 of 5 hyperglycaemic cats by day 10. The activity of lipase
      did not vary in any of the cats. Samples of exocrine pancreas were normal on
      histological examination, but the number of tissue neutrophils was increased in
      hyperglycaemic cats (P<0.05). In a retrospective study 14 of 40 (35%) cats with
      naturally occurring diabetes mellitus had amylase activities below the reference
      range at the time of admission. Amylase activities normalised within 1 week of
      insulin therapy and subsequent glycaemic control. Lipase activity was increased
      in 26 of 40 (65%) diabetic cats and remained elevated despite glycaemic control.
      In conclusion, hyperglycaemia, but not hyperlipidaemia, increases pancreatic
      neutrophils in cats. However, because the histological morphology of the exocrine
      pancreas was normal, hyperglycaemia may play only a minor role in the
      pathogenesis of pancreatitis. Low amylase activities in diabetic cats may reflect
      an imbalance in glucose metabolism rather than pancreatitis.

PMID- 20132956
TI  - Subclinical mastitis causes alterations in nitric oxide, total oxidant and
      antioxidant capacity in cow milk.
AB  - The aim of this study was to investigate total antioxidant (TAC), and oxidant
      capacity (TOC) and nitric oxide (NO) levels in milk of cows with subclinical
      mastitis. Brown Swiss and Holstein breed cows were screened with California
      Mastitis Test (CMT) to determine mammary glands with subclinical mastitis.
      Moreover, somatic cell counts (SCC) were determined electronically in all milk
      samples. Mammary quarters were classified as healthy (n=25) or subclinical
      mastitis (n=35) based on CMT scores and somatic cell count (SCC: < or =200,000/ml
      or >200,000/ml) in milk. Nitric oxide, TOC and SCC levels were significantly
      higher (p<0.001, p<0.005 and p<0.001, respectively) in milk from mammary quarters
      with subclinical mastitis compared to those from healthy mammary quarters. In
      conclusion, subclinical mastitis results in higher NO concentrations, TOC and
      SCC, and NO and TOC were positively correlated with SCC. Moreover, alterations in
      NO levels and TOC in milk could be used as an alternative diagnostic tool to
      screen for subclinical mastitis.

PMID- 20132957
TI  - Postischemic poly (ADP-ribose) polymerase (PARP) inhibition reduces ischemia
      reperfusion injury in a hind-limb ischemia model.
AB  - BACKGROUND: Several experiments were designed to determine whether the systemic,
      postischemic administration of PJ34,which is a poly-adenosine diphosphate (ADP)
      ribose polymerase inhibitor, decreased tissue injury and inflammation after hind
      limb ischemia reperfusion (I/R). METHODS: C57BL6 mouse limbs were subjected to
      1.5 h ischemia followed by 24-h reperfusion. The treatment group (PJ) received
      intraperitoneal PJ34 (30 mg/kg) immediately before reperfusion, as well as 15 min
      and 2 h into reperfusion. The control group (CG) received lactated Ringer's alone
      at the same time intervals as PJ34 administration. The skeletal muscle levels of
      adenosine triphosphate (ATP), macrophage inflammatory protein-2 (MIP-2),
      keratinocyte derived chemokine (KC), and myeloperoxidase (MPO) were measured.
      Quantitative measurement of skeletal muscle tissue injury was assessed by
      microscopic analysis of fiber injury. RESULTS: ATP levels were higher in limbs of
      PJ versus CG mice (absolute ATP: 4.7 +/- 0.35 vs 2.3 +/- 0.15-ng/mg tissue, P =
      .002). The levels of MIP-2, KC, and MPO were lower in PJ versus CG mice (MIP-2:
      1.4 +/- 0.34 vs 3.67 +/- 0.67-pg/mg protein, P = .014; KC: 4.97 +/- 0.97 vs 12.65
      +/- 3.05-pg/mg protein, P = .037; MPO: 46.27 +/- 10.53 vs 107.34 +/- 13.58-ng/mg
      protein, P = .008). Muscle fiber injury was markedly reduced in PJ versus CG mice
      (4.25 +/- 1.9% vs 22.68 +/- 3.0% total fibers, P = .0004). CONCLUSION: Systemic
      postischemic administration of PJ34 preserved skeletal muscle energy levels,
      decreased inflammatory markers, and preserved tissue viability post-I/R. These
      results support PARP inhibition as a viable treatment for skeletal muscle I/R in
      a clinically relevant post hoc scenario.

PMID- 20132958
TI  - Investigation into dyeing acceleration efficiency of ultrasound energy.
AB  - The acceleration efficiency of ultrasound was investigated by different
      application of ultrasound during dyeing process in an ultrasound cleaner. Actual
      energy dissipated into the dyeing bath was measured to ensure the formation of
      ultrasound cavatiation. The experimental findings showed ultrasound pretreatment
      could improve slightly the dye exhaustion and fixation, but failed to improve
      fastness of dyed fabrics. Obvious enhancement effects on dye exhaustion and
      fixation were achieved in continuous and intermittent ultrasound dyeing
      processes, and slight improvement effects on some fastness properties of fabrics
      dyed in ultrasound fields were observed. A comparison of the efficiencies in two
      ultrasound dyeing processes revealed the dyeing process in intermittent
      ultrasound field would benefit to making full use of ultrasound energy.

PMID- 20132959
TI  - Direct observations of colloid retention in granular media in the presence of
      energy barriers, and implications for inferred mechanisms from indirect
      observations.
AB  - In this paper we present direct observations of retention of colloids in granular
      porous media over a large size range (0.21-9.0 microm) and generalize the
      significance of attachment in grain to grain contacts and attachment on the open
      surface as a function of colloid:collector ratio. We examine reversibility of
      attachment via these mechanisms with respect to ionic strength reduction and
      fluid velocity increase. We relate these direct observations to existing
      literature, and in some cases offer alternative interpretations of mechanisms of
      retention drawn from indirect observations (e.g. via column effluent and retained
      concentrations).

PMID- 20132960
TI  - Invertebrates control metals and arsenic sequestration as ecosystem engineers.
AB  - Organic sediments are known to be a significant sink of inorganic elements in
      polluted freshwater ecosystems. Hence, we investigated the role of invertebrate
      shredders (the freshwater shrimp Gammarus pulex L.) in metal and arsenic
      enrichment into organic partitions of sediments in a wetland stream at former
      uranium mining site. Metal and metalloid content in leaf litter increased
      significantly during decomposition, while at the same time the carbon content
      decreased. During decomposition, G. pulex as a ecosystem engineer facilitated
      significantly the enrichment of magnesium (250%), manganese (560%), cobalt
      (310%), copper (200%), zinc (43%), arsenic (670%), cadmium (100%) and lead
      (1340%) into small particle sizes. The enrichments occur under very high
      concentrations of dissolved organic carbon. Small particles have high surface
      area that results in high biofilm development. Further, the highest amounts of
      elements were observed in biofilms. Therefore, invertebrate shredder like G.
      pulex can enhance retention of large amounts of metal and arsenic in wetlands.

PMID- 20132961
TI  - Development and application of dynamic air chambers for measurement of
      volatilization fluxes of benzene and MTBE from constructed wetlands planted with
      common reed.
AB  - Phytoremediation of industrially contaminated groundwater has been a proven
      technique for several decades. However, mass balances of contaminants are often
      focused in laboratory investigations. The evaluation of the transfer of volatile
      organic compounds (VOCs) under field conditions from the saturated and vadose
      soil zone into the atmosphere, directly or via plants, is rarely part of the
      research scope. This can provoke problems--particularly with regard to legal
      issues--if large-scale phytoremediation sites are situated near residential
      areas. In this study volatilization of VOCs was quantified in a horizontal-flow
      constructed wetland planted with reed grass. For this purpose, a specially
      designed air chamber was constructed, validated, and routine sampling campaigns
      were performed over the course of one year. Results indicate that the overall
      volatilization of the observed contaminants benzene and methyl tert-butyl ether
      (MTBE) depended on seasonal variations with the highest volatilization fluxes
      measured in summer, when the detected volatilization fluxes of 846+/-116 and
      252+/-11 microg m(-2) h(-1) for MTBE and benzene, respectively, accounted for
      2.4% and 5.6% of the respective overall contaminant mass loss in the planted
      wetland. Furthermore, chamber data give strong evidence for the increased
      volatilization of VOCs through vegetation by direct comparison of planted and
      unplanted wetlands.

PMID- 20132962
TI  - Can avoidance in Enchytraeus albidus be used as a screening parameter for
      pesticides testing?
AB  - Enchytraeids are important inhabitants of a wide variety of soil types and
      suitable test organisms for environmental risk assessment through the
      determination of effects on survival and reproduction. In this study, the effect
      of pesticides with different modes of action is assessed in the standard test
      species Enchytraeus albidus. Main goals were: (a) to test the toxicity of a range
      of pesticides to E. albidus in a natural soil (LUFA 2.2), (b) to assess whether
      avoidance gave a prediction of effects on the survival and reproduction, and (c)
      to investigate if the organisms' response to different toxics can be grouped into
      the respective chemical classes. Pesticides selected were the: (1) herbicides:
      phenmedipham and atrazine; (2) fungicides: carbendazim and pentachlorophenol; and
      (3) insecticides: dimethoate and lindane. All tested pesticides caused effects in
      the survival and reproduction of E. albidus and the compounds that showed a
      higher toxicity were carbendazim, dimethoate and atrazine. The effect
      concentrations were not chemical class dependent. In general, survival and
      reproduction showed similar response patterns. Avoidance behaviour showed trends
      of response similar to these other measured endpoints, but was less sensitive and
      more variable (data from a previous study). It was not possible to establish a
      clear correlation between survival, reproduction and avoidance endpoints. From an
      ecological point of view, avoidance tests are relevant but due to lower
      sensitivity and higher variability it is recommended that the enchytraeid
      avoidance test should not be used for risk assessment purposes.

PMID- 20132963
TI  - Expression of nestin in lymph node metastasis and lymphangiogenesis in non-small
      cell lung cancer patients.
AB  - Stem cell marker nestin has been reported to be activated in various neoplasms,
      and its expression is correlated with poor prognosis. However, nestin expression
      in non-small cell lung cancer still remains unclear. The present study aimed to
      investigate nestin expression in 52 tissue samples of non-small cell lung cancer
      by immunohistochemical staining and explore its correlation with some
      clinicopathologic characteristics. The associations of nestin with lymphatic
      vessel density, microvessel density, vascular endothelial growth factor, vascular
      endothelial growth factor-C, and cyclooxygenase-2 (COX-2) were further observed
      to determine the linkage between nestin and lymphangiogenesis. The results showed
      that nestin expressed in tumor cells of 45 samples. High nestin expression
      correlated significantly with poor differentiation (P = .007), adenocarcinoma (P
      = .000), N2 lymph node metastasis (P = .006), high microvessel density (P =
      .033), and lymphatic vessel density (P = .020). Multivariate analysis of N1 and
      N2 lymph node metastasis revealed a 1.086-fold increase in hazard ratio of N2
      lymph node involvement (P = .011) in patients with high nestin expression in
      primary tumor. More important, multivariate analysis showed a significant
      correlation of lymphatic vessel density with nestin and vascular endothelial
      growth factor-C expression (P = .039 and P = .045), independent of vascular
      endothelial growth factor, COX-2, and other clinicopathologic characteristics.
      The results demonstrated that nestin expressed in most tumor cells of non-small
      cell lung cancer tissue and had a direct linkage to lymph node metastasis and
      tumor-induced lymphangiogenesis, independent of COX-2 signal pathway.

PMID- 20132964
TI  - Comparison between two methods of defining heat waves: a retrospective study in
      Castile-La Mancha (Spain).
AB  - INTRODUCTION: Following the 2003 heat wave, many European countries implemented
      heat-wave prevention plans. A number of aspects can prove fundamental in
      determining the effectiveness of such plans, and of these we sought to analyse
      the criteria used to define threshold temperatures and trigger a higher level of
      intervention. METHOD: Retrospective study of the days on which heat-wave
      thresholds were exceeded during the period 1974-2003 was conducted. We compared
      when and at what level the heat-wave prevention plan would have been activated
      using a statistical-meteorological criterion (as applied by the Spanish Ministry
      of Health & Consumer Affairs) versus a temperature-mortality criterion. RESULTS:
      The number of days on which the threshold was exceeded was far higher when the
      temperature-mortality criterion was applied. The temperature percentile at which
      a heat wave occurred was different for each province analysed and was inversely
      proportional to its respective ageing index. Using both criteria, there was an
      increase in heat-wave days per decade. CONCLUSION: The establishment of a heat
      wave threshold temperature must be based on knowledge of the cause-effect
      relationship between temperature and the health of a given population. Mortality
      is an appropriate indicator of population health. The future effects of climate
      change render it essential for this relationship to be studied on a local scale,
      so as to enable truly efficient prevention plans to be drawn up.

PMID- 20132965
TI  - Serum procalcitonin in systemic autoimmune diseases--where are we now?
AB  - OBJECTIVES: To review the current evidence regarding the value of measuring
      procalcitonin (PCT) levels in patients with systemic autoimmune diseases, with a
      focus on the evidence for diagnostic and analytical performance of this
      biomarker. A brief description of the pathophysiological basis of this biomarker
      is also included. METHODS: Using PubMed from the National Library of Medicine,
      relevant English literature on PCT in patients with different systemic autoimmune
      diseases, from 1990 to 2009, was reviewed. The search used keywords referring to
      procalcitonin and systemic lupus erythematosus, antineutrophil cytoplasmic
      antibody-associated systemic vasculitis, Goodpasture syndrome, rheumatoid
      arthritis, and giant cell arteritis. RESULTS: When used in the appropriate
      clinical setting, the measurement of serum PCT levels is valuable as a marker of
      severe systemic bacterial and fungal infections and sepsis. Information regarding
      plasma PCT levels in patients with active underlying systemic autoimmune diseases
      is limited, primarily from observational studies and case series, with
      considerable variability of patient characteristics and clinical settings. In the
      detection of systemic infection concomitant with autoimmune diseases, PCT had a
      diagnostic sensitivity of 53 to 100% and a specificity of 84 to 97% (depending on
      the selection criteria) and was superior to other inflammatory markers tested.
      Most of the studies used a semiquantitative test for PCT measurement (functional
      assay sensitivity <0.5 ng/mL), which can explain the low sensitivity of the test.
      PCT levels were not significantly affected by renal function abnormalities or
      immunosuppressive agents. Although high PCT levels commonly occurred with
      infection, elevated levels of PCT could be found in patients with vasculitis
      without evidence of infection, often correlated with high disease activity
      scores. CONCLUSIONS: Significantly elevated PCT levels offer good specificity and
      sensitivity for systemic infection in patients with systemic autoimmune diseases,
      regardless of the use of corticosteroids or immunosuppressive agents. PCT
      measurement may add to diagnostic accuracy in patients with systemic autoimmune
      diseases who present with a febrile illness, especially when highly sensitive PCT
      assays and specific PCT cutoff ranges are used in a predefined clinical setting
      (reflecting the likelihood of infection versus an autoimmune disease flare).
      However, there are limitations when using this biomarker in patients with
      systemic autoimmune diseases. PCT levels should not replace the necessary
      extensive diagnostic workup, which should include a thorough history and physical
      examination, combined with appropriate immunological, microbiological,
      radiological, and histological data.

PMID- 20132966
TI  - An open-label pilot study evaluating by magnetic resonance imaging the potential
      for a disease-modifying effect of celecoxib compared to a modelized historical
      control cohort in the treatment of knee osteoarthritis.
AB  - OBJECTIVES: The aim of the study was to evaluate by quantitative magnetic
      resonance imaging the effect of celecoxib 200 mg daily on cartilage volume loss
      over 12 months in knee osteoarthritis. METHODS: The primary outcome of this study
      was to evaluate cartilage volume loss in the medial compartment of the knee
      (femoral condyle and tibial plateau) assessed by quantitative magnetic resonance
      imaging on subjects receiving continuous treatment with celecoxib 200 mg daily
      for 12 months compared with a modelized historical control cohort, as expressed
      by the percentage loss from baseline. Safety of the medication was also assessed.
      Comparison of the observed volume loss to the expected loss was evaluated by a
      multivariate linear regression model based on a historical cohort. RESULTS: For
      the primary outcome, the 95% confidence intervals for the mean observed celecoxib
      cohort joint medial compartment cartilage volume loss (6.81% [6.01; 7.60]) and
      mean predicted loss (modelized historical cohort) (5.65% [5.10; 6.19]) overlap,
      indicating no significant difference and hence no effect of celecoxib on the
      medial compartment cartilage volume loss. Similar findings were demonstrated for
      the lateral compartment cartilage loss. The safety data reported several minor
      adverse events similar to those typically seen in a 1-year clinical trial.
      CONCLUSIONS: Although celecoxib was demonstrated to be safe for knee
      osteoarthritis at a 200 mg daily dose, it did not provide a protective effect on
      knee cartilage loss. Cohort modelization is an efficient and unbiased way to
      provide a comparator group for the assessment of novel treatments when classic
      head-to-head randomized controlled trials are not feasible.

PMID- 20132967
TI  - Proliferative glomerulonephritis in lupus patients with human immunodeficiency
      virus infection: a difficult clinical challenge.
AB  - OBJECTIVES: To describe the unusual occurrence of systemic lupus erythematosus
      (SLE) with nephritis in human immunodeficiency virus (HIV)-infected individuals.
      METHODS: Chart review-based report of a case of SLE with diffuse proliferative
      glomerulonephritis (DPGN) in an HIV-infected man, together with a literature
      review of previously published cases. We searched the English language medical
      literature from 1987 to 2009 using the following PubMed and Medline terms: "SLE,"
      "HIV," "DPGN." In addition, we researched the role of mycophenolate mofetil (MMF)
      in the treatment of patients with HIV by using the keywords "MMF" and "HIV".
      RESULTS: An 18-year-old male patient with vertically transmitted HIV-1 infection
      presented with malaise, weight loss, malar rash, arthritis, proteinuria, and
      hematuria. Kidney biopsy confirmed the diagnosis of lupus nephritis (Class IV).
      He was treated successfully with high-dose corticosteroids and MMF, which were
      added to his baseline treatment of highly active antiretroviral therapy. The
      review of the literature identified a total of 18 cases of SLE appearing in HIV+
      individuals, of which 11 patients had lupus nephritis. Among the latter, there
      were only 5 cases of proliferative (focal or diffuse) glomerulonephritis, and
      their treatment consisted mainly of high-dose corticosteroids. The short-term
      outcome was favorable in 4 cases and 1 patient died. CONCLUSIONS: Proliferative
      lupus nephritis is rare in HIV-infected patients. A detailed analysis of the
      cases may lead to important insights into the pathogenic mechanisms of both
      diseases. Considering its complex interaction with antiviral medications, MMF may
      be considered for the treatment of lupus with severe proliferative
      glomerulonephritis in HIV-infected individuals.

PMID- 20132968
TI  - Pathway analysis of gene lists associated with platinum-based chemotherapy
      resistance in ovarian cancer: the big picture.
AB  - OBJECTIVE: Ovarian cancer is the leading cause of death from gynecological
      cancers in the Western world (Parkin et al., 2005). The overall 5-year survival
      is only 30% (Moss and Kaye, 2002), which is for a significant part due to
      platinum-based chemotherapy resistance. In this study, we performed a pathway
      analysis on nine published gene sets associated with platinum resistance in
      ovarian cancer, including a study by us. With this exploratory study, we aim to
      identify overlapping pathways associated with platinum-based chemotherapy
      resistance mechanisms in ovarian cancer. METHODS: Gene Ontology (GO) analysis and
      Ingenuity Pathway Analysis (IPA) were performed to determine which functional
      processes were differentially represented in the combined gene lists of nine
      studies (457 genes) compared to all Unigene identifiers or the Ingenuity
      knowledge base. RESULTS: The GO and IPA analysis resulted in the generation of 23
      gene networks, and showed that 13 GO processes (>or=2 times enriched), 71
      canonical pathways (p<0.05,), eight toxicity pathways (p<0.05) and 74 biological
      functions (p<0.005) are significantly associated with the 9-study gene set.
      CONCLUSION AND RECOMMENDATIONS: Several pathways identified have previously been
      shown to be associated with therapy resistance: these include 'oxidative stress
      response mediated by Nrf2,' 'TP53 signaling' and 'TGFbeta signaling.' The role of
      TGFbeta signaling and related miRNAs identified in the network analysis in
      epithelial-to-mesenchymal transition (EMT) and stemness as well as the possible
      relation with platin-based chemotherapy resistance are further discussed in
      detail. We propose that future international cooperation should aim at a uniform
      pooled analysis of the wealth of ovarian cancer array data already available.
      This will enhance the power of each separate ovarian cancer study and can lead to
      promising results.

PMID- 20132969
TI  - Decreases in human dendritic cell-dependent T(H)2-like responses after acute in
      vivo IgE neutralization.
AB  - BACKGROUND: Dendritic cells (DCs) and other professional antigen-presenting cells
      express a variant of the high-affinity IgE receptor known as alphagamma(2),
      which, on the basis of in vitro findings, has long been implicated to function in
      facilitating allergen uptake and presentation to T(H) cells. OBJECTIVES: To use
      omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic
      cells and to assess whether this results in altered DC-dependent T-cell
      responsiveness to allergen ex vivo. METHODS: Subjects with cat allergy were
      enrolled in a 3.5-month, double blind, randomized (3.5:1), placebo-controlled
      trial of omalizumab using standard dosing for allergic asthma. Blood plasmacytoid
      and myeloid DCs were assessed at baseline and posttreatment for expression of
      surface IgE, FcepsilonRIalpha, and induction of CD4(+)T-cell proliferation and
      cytokine responses to cat allergen. RESULTS: IgE expression on plasmacytoid and
      myeloid DCs from omalizumab-treated subjects (n = 12) decreased by > or =95%
      posttreatment (P = .0005), whereas FcepsilonRIalpha expression decreased by 66%
      and 48%, respectively (P = .0005). Cat allergen-induced proliferation in DC/T
      cell cocultures observed at baseline was suppressed approximately 20% to 40%
      postomalizumab treatment (P = .001). Multiplexing for cytokines in plasmacytoid
      DC/T-cell cocultures also showed decreases in IL-5, IL-13, and IL-10 (P < .05),
      whereas IL-2 and IFN-gamma were unaltered or slightly increased. These changes
      were not evident in placebo-control subjects (n = 4). CONCLUSION: IgE likely
      facilitates allergen presentation by dendritic cells in vivo and is also
      important in regulating DC-dependent T-cell cytokines during effector phases of
      allergic disease.

PMID- 20132970
TI  - Serum ferritin and transferrin levels are not serologic markers of toluene
      diisocyanate-induced occupational asthma.

PMID- 20132972
TI  - Evidence for neuronal expression of functional Fc (epsilon and gamma) receptors.

PMID- 20132971
TI  - Differential effects of outdoor versus indoor fungal spores on asthma morbidity
      in inner-city children.
AB  - BACKGROUND: Although sensitization to fungal allergens is prevalent in inner-city
      children with asthma, the relationship between fungal exposure and morbidity is
      poorly understood. OBJECTIVE: We examined relationships between fungal
      sensitization, exposure, and asthma morbidity in inner-city children. METHODS:
      Participants were 5 to 11 years old and enrolled in the Inner-City Asthma Study.
      This report includes the subset of children with at least 1 positive skin test
      (PST) response to a fungal allergen extract; for these children, indoor and
      outdoor airborne culturable fungi levels were measured at baseline and throughout
      the 2-year study. Asthma morbidity measures were collected prospectively. The
      primary outcome was symptom days per 2 weeks. RESULTS: At baseline, children with
      a PST response to a fungal allergen extract had significantly more symptom days
      compared with those without a PST response to any fungal allergen extract (6.3 vs
      5.7 days per 2 weeks, P = .04). During the study, increases in total fungal
      exposure and indoor Penicillium species exposure were associated with increases
      in symptom days and asthma-related unscheduled visits. Indoor exposures to total
      fungi and to Penicillium species were associated with significant increases in
      unscheduled visits, even after controlling for outdoor fungal levels. Adverse
      effects associated with exposure to a specific fungus were stronger among
      children with PST responses to that fungal allergen extract compared with those
      seen in children with negative skin test responses. CONCLUSION: Outdoor fungal
      exposure is primarily associated with increased asthma symptoms and increased
      risk of exacerbations in this population.

PMID- 20132974
TI  - Ethnic differences in asthma-panic disorder comorbidity.

PMID- 20132973
TI  - CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson
      syndrome and toxic epidermal necrolysis.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS)
      are severe, bullous cutaneous diseases with uncertain pathogenesis, although
      cytotoxic T cells seem to be involved. Natural killer (NK)-like activity has been
      found in blister infiltrates. Cytotoxic T lymphocytes (CTLs) with NK-like
      activity (NK-CTLs) have been shown to express T-cell receptors restricted by the
      HLA-Ib molecule HLA-E. Alternatively, the HLA-E-specific activating receptor
      CD94/NKG2C can trigger T-cell receptor-independent cytotoxicity in CTLs.
      OBJECTIVE: Our aim was to test whether HLA-E expression sensitizes keratinocytes
      to killing by CTLs with NK-like activity and to explore the expression of
      activating receptors specific for HLA-E in blister cytotoxic lymphocytes.
      METHODS: We used flow cytometry and immunohistochemistry to analyze HLA-E
      expression in keratinocytes from affected skin in patients with SJS, TEN, and
      other less severe drug-induced exanthemas. The expression of CD94/NKG2C was
      analyzed by means of flow cytometry in PBMCs and blister cells from patients.
      PBMCs and blister cells were analyzed for their ability to kill HLA-E-expressing
      cells. Involvement of CD94/NKG2C in triggering degranulation of cytolytic cells
      was explored by means of CD107a mobilization assays and standard cytotoxicity
      chromium release assays. RESULTS: We found that keratinocytes from affected skin
      expressed HLA-E and that cell-surface HLA-E sensitizes keratinocytes to killing
      by CD94/NKG2C(+) CTLs. Frequencies of CD94/NKG2C(+) peripheral blood T and NK
      cells were increased in patients with SJS and TEN during the acute phase.
      Moreover, activated blister T and NK lymphocytes expressed CD94/NKG2C and were
      able to degranulate in response to HLA-E(+) cells in an NKG2C-dependent manner.
      CONCLUSION: CD94/NKG2C might be involved in triggering cytotoxic lymphocytes in
      patients with SJS and TEN.

PMID- 20132975
TI  - Inflammation and airway function in the lung periphery of patients with stable
      asthma.
AB  - BACKGROUND: An important role for exhaled nitric oxide (NO) measurement could be
      in the distinction between proximal and peripheral lung contributions to
      inflammation, with a particular interest for the alveolar lung zone and its
      implication on airway function. OBJECTIVE: We aimed to isolate the acinar lung
      zone contribution to both inflammation and airway function to seek a relationship
      between them. METHODS: In 30 patients with asthma with an asthma control test
      score exceeding 20, indices of conductive and acinar ventilation heterogeneity
      (Scond, Sacin) were obtained from a multiple breath washout. NO production in the
      conductive airways (J'aw(NO)), alveolar NO concentration (CA(NO)), and the
      standard exhaled NO at 50 mL/s (FENO(50)) were obtained from exhaled NO. RESULTS:
      Scond was consistently abnormal in all patients with stable asthma, but without
      any correlation to inflammation abnormality in that compartment (J'aw(NO)). Sacin
      was particularly abnormal in the asthma subgroup receiving >500 microg budesonide
      equivalent, and a correlation was found between Sacin and CA(NO) (r = 0.61; P =
      .015); in this subgroup, a weak association was found between Scond and J'aw(NO)
      or FENO(50) (r = 0.50; P = .059 for both). CONCLUSION: The persistent functional
      abnormality of small conductive airways in patients with stable asthma is largely
      independent of inflammation as measured by exhaled NO. In the alveolar
      compartment, a functional correlate of alveolar NO was found in a subgroup of
      patients with stable asthma on moderate-to-high maintenance doses of inhaled
      steroids. These patients in particular could benefit from novel therapies
      specifically aimed at improving airway functionality at the level of the acinar
      entrance and beyond.

PMID- 20132976
TI  - Naturally processed T cell-activating peptides of the major birch pollen
      allergen.
AB  - BACKGROUND: Although antigen processing and presentation of allergens to CD4(+)T
      lymphocytes are key events in the pathophysiology of allergic disorders, they
      still remain poorly understood. OBJECTIVE: To investigate allergen processing and
      presentation by dendritic cells using the major birch pollen allergen Bet v 1 as
      a model. METHODS: Endolysosomal extracts of dendritic cells derived from patients
      with birch pollen allergy were used to digest Bet v 1. Dendritic cells were
      pulsed with Bet v 1, and peptides were eluted from MHC class II molecules.
      Peptides obtained by either approach were sequenced by tandem mass spectrometry.
      Bet v 1-specific T-cell cultures were stimulated with HLA-DR-eluted Bet v 1
      derived peptides. Bet v 1-specific T-cell lines were generated from each patient
      and analyzed for epitope recognition. RESULTS: A high proportion of Bet v 1
      remained intact for a long period of endolysosomal degradation. The peptides that
      appeared early in the degradation process contained frequently recognized T-cell
      epitopes. Bet v 1-derived peptides eluted from MHC class II molecules
      corresponded to those generated by endolysosomal degradation, matched known T
      cell epitopes, and showed T cell-activating capacity. The Bet v 1-specific T-cell
      line of each individual harbored T cells reactive with peptides located within
      the MHC class II-eluted Bet v 1-derived sequences demonstrating their occurrence
      in vivo. CONCLUSION: We report for the first time how epitopes of allergens are
      generated and selected for presentation to T lymphocytes. The limited
      susceptibility of Bet v 1 to endolysosomal processing might contribute to its
      high allergenic potential.

PMID- 20132977
TI  - Brain embodiment of syntax and grammar: discrete combinatorial mechanisms spelt
      out in neuronal circuits.
AB  - Neuroscience has greatly improved our understanding of the brain basis of
      abstract lexical and semantic processes. The neuronal devices underlying words
      and concepts are distributed neuronal assemblies reaching into sensory and motor
      systems of the cortex and, at the cognitive level, information binding in such
      widely dispersed circuits is mirrored by the sensorimotor grounding of form and
      meaning of symbols. Recent years have seen the emergence of evidence for similar
      brain embodiment of syntax. Neurophysiological studies have accumulated support
      for the linguistic notion of abstract combinatorial rules manifest as
      functionally discrete neuronal assemblies. Concepts immanent to the theory of
      abstract automata could be grounded in observations from modern neuroscience, so
      that it became possible to model abstract pushdown storage - which is critical
      for building linguistic tree structure representations - as ordered dynamics of
      memory circuits in the brain. At the same time, neurocomputational research
      showed how sequence detectors already known from animal brains can be neuronally
      linked so that they merge into larger functionally discrete units, thereby
      underpinning abstract rule representations that syntactically bind lexicosemantic
      classes of morphemes and words into larger meaningful constituents. Specific
      predictions of brain-based grammar models could be confirmed by
      neurophysiological and brain imaging experiments using MEG, EEG and fMRI.
      Neuroscience and neurocomputational research offering perspectives on
      understanding abstract linguistic mechanisms in terms of neuronal circuits and
      their interactions therefore point programmatic new ways to future theory-guided
      experimental investigation of the brain basis of grammar.

PMID- 20132978
TI  - Identifying sick children in primary care.

PMID- 20132979
TI  - Diagnostic value of clinical features at presentation to identify serious
      infection in children in developed countries: a systematic review.
AB  - BACKGROUND: Our aim was to identify which clinical features have value in
      confirming or excluding the possibility of serious infection in children
      presenting to ambulatory care settings in developed countries. METHODS: In this
      systematic review, we searched electronic databases (Medline, Embase, DARE,
      CINAHL), reference lists of relevant studies, and contacted experts to identify
      articles assessing clinical features of serious infection in children. 1939
      potentially relevant studies were identified. Studies were selected on the basis
      of six criteria: design (studies of diagnostic accuracy or prediction rules),
      participants (otherwise healthy children aged 1 month to 18 years), setting
      (ambulatory care), outcome (serious infection), features assessed (assessable in
      ambulatory care setting), and sufficient data reported. Quality assessment was
      based on the Quality Assessment of Diagnostic Accuracy Studies criteria. We
      calculated likelihood ratios for the presence (positive likelihood ratio) or
      absence (negative likelihood ratio) of each clinical feature and pre-test and
      post-test probabilities of the outcome. Clinical features with a positive
      likelihood ratio of more than 5.0 were deemed red flags (ie, warning signs for
      serious infection); features with a negative likelihood ratio of less than 0.2
      were deemed rule-out signs. FINDINGS: 30 studies were included in the analysis.
      Cyanosis (positive likelihood ratio range 2.66-52.20), rapid breathing (1.26
      9.78), poor peripheral perfusion (2.39-38.80), and petechial rash (6.18-83.70)
      were identified as red flags in several studies. Parental concern (positive
      likelihood ratio 14.40, 95% CI 9.30-22.10) and clinician instinct (positive
      likelihood ratio 23.50, 95 % CI 16.80-32.70) were identified as strong red flags
      in one primary care study. Temperature of 40 degrees C or more has value as a red
      flag in settings with a low prevalence of serious infection. No single clinical
      feature has rule-out value but some combinations can be used to exclude the
      possibility of serious infection-for example, pneumonia is very unlikely
      (negative likelihood ratio 0.07, 95% CI 0.01-0.46) if the child is not short of
      breath and there is no parental concern. The Yale Observation Scale had little
      value in confirming (positive likelihood ratio range 1.10-6.70) or excluding
      (negative likelihood ratio range 0.16-0.97) the possibility of serious infection.
      INTERPRETATION: The red flags for serious infection that we identified should be
      used routinely, but serious illness will still be missed without effective use of
      precautionary measures. We now need to identify the level of risk at which
      clinical action should be taken. FUNDING: Health Technology Assessment and
      National Institute for Health Research National School for Primary Care Research.

PMID- 20132980
TI  - PLGA nanoparticles surface decorated with the sialic acid, N-acetylneuraminic
      acid.
AB  - There is a broad interest in the development of nanoparticles (NPs) carrying on
      their surface carbohydrates such as sialic acids. It is known that these
      carbohydrates influence the biological and physical properties of
      biopharmaceutical proteins and living cells. Macromolecular compounds containing
      these carbohydrates showed an anti-recognition effect, exert an antiviral effect
      and also are able to be recognized by the cell surface of some kind of cancer
      cells. Thus, in the present research we performed two different approaches in
      order to obtain polymeric (poly(D,L-lactide-co-glycolide), PLGA) NPs surface
      decorated with the sialic acid N-acetylneuraminic acid (Neu5Ac). The first
      strategy that has been followed is based on the derivatization of the polyester
      PLGA with the thioderivative of Neu5Ac, starting material for the preparation of
      the NPs; the second is based on the synthesis of compounds potentially able to
      insert their lipophilic moiety into the underivatized PLGA NPs during their
      preparation, and to display their hydrophilic moiety (Neu5Ac) on their surface.
      The first approach allowed the obtainment of NPs surface decorated with Neu5Ac,
      as evidenced by ESCA spectroscopy and interaction with the lectin Wheat Germ
      Agglutinin. Moreover, a formulation of these NPs suitable for in vitro assays
      showed that they are phagocytosed by human monocytes with an apparently different
      mechanism with respect of those made of underivatized PLGA. The second strategy
      led to NPs in which their surface appears to be very different with respect to
      the NPs obtained following the first strategy, with the carboxylic groups of
      Neu5Ac markedly shielded. Thus, the new Neu5Ac-modified PLGA polyester represent
      a useful starting material for the preparation of NPs surface decorated with this
      sialic acid.

PMID- 20132981
TI  - The performance of bone marrow mesenchymal stem cell--implant complexes prepared
      by cell sheet engineering techniques.
AB  - This study investigated the hypothesis that cell sheets composed of multilayered
      rabbit bone marrow derived mesenchymal stem cells (MSC) could be assembled with
      two kinds of implants (surface-modified titanium and zirconia) for the
      construction of a MSC-implant. The MSC sheets were harvested from culture flasks,
      wrapped around implants to construct the complexes, and then cultured in
      osteogenic medium. The layered cell sheets integrated well with implants and
      remained viable, with small mineralized nodules visible on the implant surfaces
      for up to four weeks after culture. Cells on the implants underwent classical in
      vitro osteogenic differentiation with an associated elevation of alkaline
      phosphatase activity and bone- and vascular-related protein expression. In vivo,
      two kinds of cell sheet-implant complexes were transplanted under the skin of
      SCID mice and cultured for eight weeks. For the MSC sheet titanium implant
      complex, histological examination revealed that new bone tissue that formed
      around implants followed a predominantly endochondral pathway, exhibiting
      histological markers of native bone; for the MSC sheet zirconia implant complex,
      however, intramembranous ossification appeared to occur on the surface of the
      zirconia implant, as observed with typical osteocytes embedded in dense matrix
      and accompanied by both microvessels and marrow cavities. These findings
      demonstrate that MSC-implants possessing osteogenic and vascularization abilities
      can be produced using cell sheet engineering techniques in conjunction with
      routine implant materials, which provide a novel technology to modify the implant
      surface.

PMID- 20132982
TI  - Dual-modality in vivo imaging using rare-earth nanocrystals with near-infrared to
      near-infrared (NIR-to-NIR) upconversion luminescence and magnetic resonance
      properties.
AB  - Upconversion luminescence (UCL) imaging is expected to play a significant role in
      future photoluminescence imaging since it shows advantages of sharp emission
      lines, long lifetimes, superior photostability and no blinking. To further
      improve penetration depth, herein, near-infrared to near-infrared (NIR-to-NIR)
      UCL and magnetic properties were combined into a nanoparticle, and NIR-to-NIR UCL
      and MRI dual-modal bioimaging in vivo of whole-body animal were developed.
      Hydrophilic and carboxylic acid-functionalized Tm(3+)/Er(3+)/Yb(3+) co-doped
      NaGdF(4) upconversion nanophosphors (AA-NPs) were synthesized and showed both NIR
      to-visible and NIR-to-NIR luminescence under excitation of 980 nm. Collecting the
      signal of the upconversion emission from AA-NPs in the visible and NIR range, all
      UCL imaging of cells, tissues and whole-body animals with different penetration
      depth showed high contrast. Moreover, AA-NPs showed a high relaxivity of 5.60 s(
      1) (mM)(-1) and were successfully applied as contrast agents for magnetic
      resonance imaging (MRI) in vivo. By means of the combination of UCL imaging and
      MRI, the distribution of AA-NPs in living animals was studied, and the results
      indicated that these particles mainly accumulate in the liver and spleen without
      undesirable stay in the lungs. Therefore, the concept of UCL and MR dual-modality
      imaging in vivo of whole-body animals using Tm(3+)/Er(3+)/Yb(3+) co-doped
      NaGdF(4) with NIR-to-NIR upconversion luminescent and magnetic resonance
      properties can serve as a platform technology for the next-generation of probes
      for bioimaging in vivo.

PMID- 20132983
TI  - The effect of hydrofluoric acid treatment on titanium implant osseointegration in
      ovariectomized rats.
AB  - This study aimed to investigate the effects of hydrofluoric acid (HF) treatment
      of grit-blasted Ti implants on osseointegration in ovariectomized (OVX) rats.
      After blasting with aluminium oxide particles, half implants were treated with
      0.2 vol.% HF, and the other half were kept non-modified as control. The
      topographical and chemical changes of implant surface were determined by Scanning
      Electron Microscope, Atomic Force Microscope, and X-ray Photoemission
      Spectroscopy. 12 Weeks after bilateral ovariectomy, each rat accepted two
      implants in distal femora, with the control implant on the left and the fluoride
      modified on the right. As a result, fluoride modification induced markedly
      changed surface topography and chemical composition. 12 Weeks after implant
      insertion, the fluoride-modified implants showed improved osseointegration
      compared to control, with the bone area ratio and bone-to-implant contact
      increased by 0.9- and 1.4-fold in histomorphometry, the bone volume ratio and
      percent osseointegration by 0.8- and 1.3-fold in micro-CT evaluation, and the
      maximal push-out force and ultimate shear strength by 1.2- and 2.0-fold in
      biomechanical test. These promising results indicated that HF treatment of Ti
      surface improved implant osseointegration in OVX rats, and suggested the
      feasibility of using fluoride modification to improve Ti implant osseointegration
      in osteoporotic bone.

PMID- 20132984
TI  - Lack of association between unexplained elevated maternal serum alpha fetoprotein
      and/or human chorionic gonadotropin and the occurrence of placental thrombotic
      lesions.
AB  - OBJECTIVE: To investigate the significance of unexplained elevated maternal serum
      alpha fetoprotein (MSAFP) and/or human chorionic gonadotropin (HCG) on the
      occurrence of placental thrombotic changes. STUDY DESIGN: Between January 2007 to
      April 2009, placentas of all women who delivered and had unexplained elevated
      MSAFP and/or HCG (above 2 MOM) were sent to histological examination. Women were
      divided into 2 groups. Group A included women who had uneventful pregnancies and
      delivered at term. Group B included women with antepartum complications
      attributed to thrombosis. Women in both groups (A and B) had elevated MSAFP
      and/or HCG. Group C was a frequency matched group of women who had normal MSAFP
      and HCG levels with uneventful pregnancies and delivered at term. MAIN OUTCOME
      MEASURE: Incidence of placental thrombotic lesions in each group. RESULTS: Of
      9695 women who delivered during the study period there were 76 women with
      elevated MSAFP and or HCG, 48 in group A and 28 in Group B. Group C, included 30
      women. The number of placentas in which any thrombotic lesion was identified was
      22 (45.8%), 19 (67.9%) and 10 (33%) respectively. Changes differed significantly
      only between group B and C (p = 0.03). Although the rate of changes in group A
      was higher than in group C it did not reach statistical significance even when
      considering only women with two abnormal results (MSAFP and HCG) or when a cutoff
      of 2.5 MOM or more was set. CONCLUSION: Placental histopathological changes are
      associated with pregnancy complications and can only marginally be attributed to
      unexplained elevated MSAFP and/or HCG.

PMID- 20132985
TI  - A multibiomarker approach in Coris julis living in a natural environment.
AB  - To monitor the health of aquatic organisms, biomarkers have been used as
      effective tools in assessing environmental risk. In this study was examined the
      teleost Coris julis, sampled in two marine sites in Messina (Italy) at different
      pollution degree, Milazzo, characterized by a strong anthropogenic impact, and
      Marinello, the natural reserve. C. julis is a species particularly suitable to
      biomonitoring because its feeding habits favor bio-accumulation of xenobiotics.
      The following biomarkers were used to estimate the impact of highly persistent
      pollutants: cellular localization of cytochrome P4501A (CYP1A) and glutathione-S
      transferase (GST) in the liver, their hepatic expression at the mRNA level, the
      enzymatic activity (EROD and BPMO), the micronucleus and comet assays in the
      blood, esterases (AChE in the brain and BChE in the blood) activity and
      evaluation of PAH metabolites in the bile. The present findings provide evidence
      of statistically significant differences in parameters between individuals
      collected in two sites.

PMID- 20132986
TI  - Molecular characterization of Pleurodeles waltl activation-induced cytidine
      deaminase.
AB  - Activation-induced cytidine deaminase (AID) is involved in immunoglobulin
      affinity maturation, gene conversion and class switch recombination. This protein
      is therefore a major actor in the creation of the antibody repertoire. We have
      isolated, for the first time, the AID mRNA from a urodele amphibian, Pleurodeles
      waltl. This mRNA encodes 198 amino acids and shares 70% and 76% of similarity
      with Xenopus laevis and human AID sequences, respectively. All consensus motifs
      necessary for AID functions are present, suggesting that AID is functional in P.
      waltl. P. waltl AID is encoded by five exons as in other species. However, in
      contrast to mammalian AID, no splice variant could be detected in that species.
      We also noted that AID is predominantly expressed in the spleen, the major
      secondary lymphoid organ of P. waltl, and that the transcriptional regulation of
      P. waltl AID is partially different from that found in higher vertebrates.
      Furthermore, we showed that AID is expressed early during P. waltl embryonic
      development.

PMID- 20132987
TI  - Foveal anatomic changes in a progressing stage 1 macular hole documented by
      spectral-domain optical coherence tomography.
AB  - OBJECTIVE: To report the case of a stage 1 macular hole and the sequential
      intrafoveal changes with spectral-domain optical coherence tomography (SD-OCT).
      DESIGN: Single, observational case report. PARTICIPANT: A 51-year-old woman with
      a stage 1A macular hole that progressed to a stage 2 macular hole. METHODS:
      Clinical ophthalmologic examinations were repeated, including SD-OCT, during
      follow-up at intervals of several weeks. MAIN OUTCOME MEASURES: Sequential
      intrafoveal tomographic alterations in a patient with a stage 1 macular hole.
      Foveal splits in the inner retina progressed to an enlarged pseudocyst that
      disrupted the outer retinal layer (ORL) resulting from the vitreous traction
      associated with a perifoveal posterior vitreous detachment (PPVD). RESULTS: The
      patient was referred for decreased vision in the left eye. Her best-corrected
      visual acuity was 20/32 in the left eye. The SD-OCT showed intrafoveal splits of
      a typical stage 1A macular hole with a PPVD. Two weeks later, a small,
      triangularly shaped foveal detachment was detected beneath the central fovea.
      Four weeks after the initial visit, the splits expanded and the foveal surface
      was elevated anteriorly; a columnar structure between the splits beneath the
      central fovea was seen. Eight weeks after the initial visit, the columnar
      structure was pulled from the outer retina with formation of the PPVD; the
      structure had shortened anteriorly and formed a cone-shaped structure under the
      roof. Eleven weeks after the initial visit, the cone-shaped structure shortened
      and became smaller under the inner roof, and the ORL was separated completely.
      The anatomic features of the foveal pseudocyst were comparable with that of a
      typical stage 1B macular hole. Eighteen weeks after the initial visit, the cone
      shaped structure disappeared under the inner roof. Thirty weeks after the initial
      visit, the roof opened with formation of the PPVD. The foveal anatomic features
      of the full-thickness macular hole became comparable with that of a typical stage
      2 macular hole. CONCLUSIONS: These OCT findings suggested that the cone-shaped
      structure was pulled from the outer retina by anteroposterior vitreous traction.
      This may cause a progressively enlarging pseudocyst that disrupts the ORL in some
      cases of stage 1 macular holes. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 20132988
TI  - Beta-Zone parapapillary atrophy and the velocity of glaucoma progression.
AB  - PURPOSE: Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with
      glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and
      without beta-zone PPA at the time of baseline assessment were compared. DESIGN:
      Retrospective, comparative study. PARTICIPANTS: Two hundred forty-five patients
      from the New York Glaucoma Progression Study. METHODS: Subjects with glaucomatous
      optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with
      a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests
      after the HRT in either eye, optic disc photographs, and <6 diopters of myopia
      were enrolled. beta-Zone PPA was defined as a region of chorioretinal atrophy
      with visible sclera and choroidal vessels adjacent to the optic disc. Global
      rates of VF progression were determined by automated pointwise linear regression
      analysis. Univariate analysis included age, gender, ethnicity, central corneal
      thickness (CCT), refractive error, baseline mean deviation, baseline intraocular
      pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc
      area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and
      presence or absence of beta-zone PPA. MAIN OUTCOME MEASURES: The relationship
      between beta-zone PPA and the rate and risk of glaucoma progression. RESULTS: Two
      hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were
      enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after
      HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta
      zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (
      0.51+/-0.6 dB/year; P<0.01). Multivariate regression showed significant influence
      of mean IOP (hazard ratio [HR], 1.11; P<0.01), IOP fluctuation (HR, 1.17; P =
      0.02), and presence of beta-zone PPA (HR, 2.59; P<0.01) on VF progression.
      Moderate (0.5-1.5 dB/year; P = 0.01) and fast (>1.5 dB/year; P = 0.08) global
      rates of progression occurred more commonly in eyes with beta-zone PPA than in
      eyes without it. Thinner CCT (<525 microm) had a weak but significant correlation
      with presence of beta-zone PPA (kappa = 0.13). CONCLUSIONS: Eyes with beta-zone
      PPA are at increased risk for glaucoma progression and warrant close clinical
      surveillance.

PMID- 20132989
TI  - Phenotype and genotype characteristics of age-related macular degeneration in a
      Japanese population.
AB  - PURPOSE: To describe phenotype and genotype characteristics of age-related
      macular degeneration (AMD) in Japanese patients. DESIGN: A case-control study.
      PARTICIPANTS: A total of 550 case-control samples composed of 408 consecutive AMD
      cases and 142 controls. METHODS: Clinical information assessing age, gender,
      affected eyes, fundus features, and fluorescein/indocyanine green angiograms were
      systematically evaluated. Four single nucleotide polymorphisms (SNPs; rs800292,
      rs1061170, rs1410996, rs2274700) in the complement factor H (CFH) gene, 1 SNP
      (rs11200638) in the high-temperature requirement factor A1 (HTRA1) gene, 3 SNPs
      (rs699947, rs1570360, rs2010963) in the vascular endothelial growth factor (VEGF)
      gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the pigment
      epithelium-derived factor (PEDF) gene were assessed using TaqMan technology. MAIN
      OUTCOME MEASURES: The clinical phenotype information and genotypes of CFH, HTRA1,
      VEGF, and PEDF polymorphisms. RESULTS: Of Japanese patients with neovascular AMD
      (nAMD), 219 (58.7%) had typical nAMD and 154 (41.3%) had polypoidal choroidal
      vasculopathy (PCV). The frequency of bilateral exudative involvement was similar
      between typical nAMD (15.5%) and PCV (13.6%) (P = 0.613). Significant soft drusen
      were observed in the fellow eyes of 88 (47.6%) of 185 patients with unilateral
      typical nAMD and in 25 (18.8%) of 133 patients with unilateral PCV (P = 1.24x10(
      7)). A serous pigment epithelium detachment was seen in 55 (25.1%) of 219
      patients with typical nAMD and in 64 (41.6%) of 154 patients with PCV. A
      significant association was noted in CFH-rs800292, CFH-rs1410996, CFH-rs2274700,
      and HTRA1-rs11200638 with AMD development (P = 2.36x10(-5), 7.18x10(-5), 7.18x10(
      5), 2.70x10(-7), respectively; population attributable risk = 57.3%, 57.8%,
      57.8%, and 58.9%, respectively). We estimated the highest-risk group to have an
      approximately 70-fold greater risk of nAMD compared with the lowest-risk group
      when analyzing a combination of 4 SNPs in the CFH and HTRA1 genes. CONCLUSIONS:
      The Japanese AMD phenotype is characterized by a higher frequency of PCV, male
      predominance, and lower frequency of bilateral presentation compared with
      Caucasian AMD. Genotype analyses demonstrate a significant population
      attributable risk for SNPs in the CFH and HTRA1 genes and demonstrate joint
      effects for both genes. Gene variants in both CFH and HTRA1 contribute
      significantly to the AMD phenotype in a Japanese population.

PMID- 20132990
TI  - Statins for the treatment of obstetric complications in antiphospholipid
      syndrome?

PMID- 20132991
TI  - Is there a CSF biomarker profile related to depression in elderly women?
AB  - In light of our previous observation of higher levels of cerebrospinal fluid
      (CSF) amyloid beta-42 (Abeta42) and CSF/serum albumin ratio in major depressive
      disorder (MDD), we analyzed two additional CSF biomarkers reflecting
      neurodegeneration-neurofilament protein light (NFL) and glial fibrillary acidic
      protein (GFAp)-in relationship to prevalent geriatric depression.
      Neuropsychiatric, physical, and lumbar puncture examinations, with DSM-III-R
      based depression diagnoses and measurement of CSF levels of NFL and GFAp, were
      evaluated among a population-based sample of 78 elderly women (mean age, 73.9+/
      3.2 years) without dementia for at least 10 years after CSF collection. Eleven
      (13.1%) women had MDD, and higher levels of NFL compared with women without
      depression. A multivariate model including age, NFL, Abeta42 and the CSF/serum
      albumin ratio showed that each biomarker was independently and positively
      associated with MDD, and that this biomarker profile explained more variation in
      the model compared with single or combined biomarkers. A CSF profile with higher
      levels of NFL, Abeta42, and CSF/serum albumin ratio may indicate
      neuropathological and vascular events in depression etiology. This contrasts with
      the well-characterized pattern of low Abeta42, higher CSF/serum albumin ratio,
      and higher NFL in Alzheimer's disease.

PMID- 20132992
TI  - Morningness-eveningness and depression: preliminary evidence for the role of the
      behavioral activation system and positive affect.
AB  - There is considerable evidence of circadian rhythm abnormalities in mood
      disorders. Morningness-eveningness, the degree to which people prefer organizing
      their activity and sleep patterns toward the morning or evening, is related to
      circadian phase and is associated with mood, with relatively greater
      psychological distress among evening types. Given that circadian rhythms may also
      relate to the Behavioral Activation System (BAS) and positive affect (PA), but
      not to the Behavioral Inhibition System (BIS) or negative affect (NA), it was
      hypothesized that individual differences in BAS sensitivity and levels of PA, but
      not BIS and NA, would explain the association between morningness-eveningness and
      depression in a sample of 208 individuals with a range of depressive
      symptomatology. As predicted, increasing eveningness was associated with greater
      depression, lower BAS, and lower PA, but not directly associated with NA. Path
      analyses supported a model wherein morningness-eveningness is associated with
      depression via multi-step indirect paths including BAS-Reward Responsiveness, PA,
      and NA. A path between BIS and depression was distinct from the one involving
      morningness-eveningness. A variety of alternative path models all provided a
      weaker fit to the data. Thus, results were consistent with the BAS and PA
      mediating the effects of morningness-eveningness on depression.

PMID- 20132993
TI  - Analysis of peripheral immune activation in schizophrenia using quantitative
      reverse-transcription polymerase chain reaction (RT-PCR).
AB  - Immune system abnormalities in schizophrenia include a shift from a Type 1
      (cellular) to a Type 2 (humoral) immune response. To characterize the activation
      status of the immune system in schizophrenia, we examined the pattern of gene
      expression in peripheral blood cells for three Th1 cytokines (interferon-gamma
      (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2)), and
      one Th2 cytokine (interleukin-10 (IL-10)). In a cross-sectional study, we used
      quantitative reverse-transcription polymerase chain reaction (RT-PCR) to compare
      the mRNA levels of IFN-gamma, TNF-alpha, IL-2, and IL-10 in peripheral blood
      mononuclear cells (PBMCs) between 15 schizophrenia patients and 15 matched
      healthy controls. Expression of IFN-gamma and TNF-alpha was significantly reduced
      in patients with schizophrenia compared with normal controls. No differences in
      IL-2 and IL-10 gene expression were observed. These results are consistent with
      impaired Type 1 cellular immunity in schizophrenia. While the data illustrate the
      potential utility of mRNA-based approaches for the identification and analysis of
      immune biomarkers for neuropsychiatric disorders, correlation of gene expression
      with direct measures of cytokine concentrations is required.

PMID- 20132994
TI  - Diminished CD4+/CD25+ T cell and increased IFN-gamma levels occur in dogs
      vaccinated with Leishmune in an endemic area for visceral leishmaniasis.
AB  - The Leishmune vaccine has been used in endemic areas to prevent canine visceral
      leishmaniasis in Brazil, but cytokine production induced by vaccination has
      rarely been investigated in dogs. This study aimed to evaluate the immune
      response of dogs vaccinated with Leishmune FML vaccine (Fort Dodge) against total
      antigen of Leishmania (Leishmania) chagasi (TAg) and FML. Twenty healthy dogs
      from Aracatuba, Sao Paulo, Brazil, an endemic leishmaniasis area, received three
      consecutive subcutaneous injection of Leishmune vaccine at 21-day intervals. PBMC
      were isolated before and 10 days after completing vaccination and
      lymphoproliferative response and antibody production against FML or total
      promastigote antigen were tested. Cytokines IFN-gamma, IL-4 and TNF-alpha were
      measured in culture supernatant and CD4+/CD25+ and CD8+/CD25+ T cell presence was
      determined. Analysis of the data indicated that the vaccine conferred humoral
      responses (100%) against both antigens and cellular immunity to FML (85%) and
      total antigen (80%), the supernatant of cultured cells stimulated with TAg and
      FML showed an increase in IFN-gamma (P<0.05), and the vaccine reduced CD4+/CD25+
      T cell presence compared to that observed before vaccination. These responses may
      constitute part of the immune mechanism induced by Leishmune.

PMID- 20132995
TI  - Evaluation of sensitivity and specificity of routine meat inspection of Danish
      slaughter pigs using Latent Class Analysis.
AB  - Two groups of observers, regular meat inspectors and two veterinary researchers,
      respectively, conducted independent veterinary meat inspection of organs of
      slaughter pigs from organic or conventional production systems slaughtered at one
      abattoir in April 2005. A total of 3054 pigs (899 organic and 2155 conventional)
      were examined. The observed pathological disorders were grouped in four
      categories; respiratory disorders (RESP), parasitic disorders (PAR), intestinal
      disorders (INT) and heart disorders (HEART). Using a latent class model, the
      sensitivity (Se) and specificity (Sp) of meat inspectors and researchers were
      estimated without the assumption of an available gold standard. The Se for the
      regular meat inspection was found to be 0.92, 0.16, 0.24 and 0.49 for RESP, PAR,
      INT and HEART, respectively. The Se for the researchers was found to be 0.81,
      0.96, 0.91 and 0.68 for RESP, PAR, INT and HEART, respectively. The Sp for the
      regular meat inspection was found to be between 0.98 and 1.00 for the four
      categories. The Sp for the researchers was found to be 0.83, 0.94, 0.76 and 0.99
      for RESP, PAR, INT and HEART, respectively. The low Se of ordinary meat
      inspection for parasitic, intestinal and heart disorders will cause a significant
      underestimation of the prevalence of diseases reported to the pig producers.
      Based on our results the true prevalence of diseases (conventional vs. organic
      slaughter pigs) was (in %): 42 vs. 16, 5 vs. 51, 5 vs. 12 and 9 vs. 5 for RESP,
      PAR, INT and HEART, respectively.

PMID- 20132996
TI  - Staphylococcal strains adapted to epigallocathechin gallate (EGCG) show reduced
      susceptibility to vancomycin, oxacillin and ampicillin, increased heat tolerance,
      and altered cell morphology.
AB  - Epigallocathechin gallate (EGCG) possesses many beneficial properties, such as
      anticarcinogenicity, antiatherogenicity, as well as antioxidant and antibacterial
      activities. However, the bacterial response to sublethal concentrations of EGCG
      has not been studied. Here we investigated whether short exposure of
      staphylococci strains to sublethal doses of EGCG can lead to adaptation and cross
      resistance. Two-hour exposure of five strains to 20 microg/ml of EGCG did not
      affect the growth rate but significantly elevated the resistance towards
      antibiotics targeting the bacterial cell wall. The magnitude of cross-resistance
      towards such antibiotics varied with the staphylococci strain, with
      Staphylococcus aureus Newman exhibiting the highest magnitude of cross
      resistance, showing a 2, 4 and 8-fold increase in resistance towards vancomycin,
      oxacillin and ampicillin respectively. All EGCG-adapted strains were also more
      heat tolerant than their control counterparts as derived from the Weibull model.
      Adaptation to EGCG led to a moderate increase in heat resistance of the adapted
      strains S. epidermis ATCC 12228, S. aureus Newman, and S. aureus ATCC 29213, and
      an extremely pronounced increase for S. aureus ATCC 6538 and S. aureus RN4220.
      The shape of the survival curve also varied with the staphylococci strain.
      Transmission electron microscopy (TEM) analysis revealed suppressed separation of
      daughter cells in cultures exposed to EGCG, as evidenced by the
      pseudomulticellular appearance and by more than 2-fold increase in cell wall
      thickness. These observations raise concerns over the potential of EGCG
      utilization in therapy in that it may contribute to the development and
      enhancement of microbial resistance mechanisms.

PMID- 20132997
TI  - Three novel mutations in MODY and its phenotype in three different Czech
      families.
AB  - AIMS/HYPOTHESIS: MODY (Maturity Onset Diabetes of the Young) is an autosomal
      dominant inherited type of diabetes with significant genetic heterogeneity. New
      mutations causing MODY are still being found. A genetically confirmed diagnosis
      of MODY allows application of individualized treatment based on the underlying
      concrete genetic dysfunction. Detection of novel MODY mutations helps provide a
      more complete picture of the possible MODY genotypes. MATERIALS AND METHODS: We
      tested 43 adult Czech patients with clinical characteristics of MODY, using
      direct sequencing of HNF1A (hepatocyte nuclear factor 1-alpha), HNF4A (hepatocyte
      nuclear factor 4-alpha) and GCK (glucokinase) genes. RESULTS: In three Czech
      families we identified three novel mutations we believe causing MODY-two missense
      mutations in HNF1A [F268L (c.802T>C) and P291S (c.871C>T)] and one frame shift
      mutation in GCK V244fsdelG (c.729delG). Some of the novel HNF1A mutation carriers
      were successfully transferred from insulin to gliclazide, while some of the novel
      GCK mutation carriers had a good clinical response when switched from insulin or
      oral antidiabetic drugs to diet. CONCLUSION: We describe three novel MODY
      mutations in three Czech families. The identification of MODY mutations had a
      meaningful impact on therapy on the mutation carriers.

PMID- 20132999
TI  - Normal to increased thrombin generation in patients undergoing liver
      transplantation despite prolonged conventional coagulation tests.
AB  - BACKGROUND & AIMS: Patients with liver disease often show substantial changes in
      their hemostatic system, which may aggravate further during liver
      transplantation. Recently, thrombin generation in patients with stable disease
      was shown to be indistinguishable from controls provided thrombomodulin, the
      natural activator of the anticoagulant protein C system, was added to the plasma.
      These results indicated that the hemostatic balance is preserved in patients with
      liver disease, despite conventional coagulation tests suggest otherwise. METHODS:
      Here we examined thrombin generation profiles in serial plasma samples taken from
      ten consecutive patients undergoing liver transplantation. RESULTS: At all time
      points, the endogenous thrombin potential (ETP) was slightly lower compared to
      healthy volunteers, despite substantially prolonged PT and APTT values. However,
      when thrombin generation was tested in the presence of thrombomodulin, the ETP
      was equal to or even higher than that in healthy subjects. In fact, thrombin
      generation was hardly affected by thrombomodulin, while thrombin generation in
      healthy subjects decreased profoundly upon the addition of thrombomodulin. In
      patients undergoing liver transplantation, efficient thrombin generation in the
      presence of thrombomodulin may be explained by decreased levels of protein C, S,
      and antithrombin, and by elevated levels of FVIII. CONCLUSIONS: Thrombin
      generation in patients undergoing liver transplantation is equal or even superior
      to thrombin generation in healthy volunteers when tested in the presence of
      exogenous thrombomodulin. These results support the recently advocated
      restrictive use of plasma during liver transplantation and warrants further study
      of the prophylactic use of anticoagulants to reduce thromboembolic complications
      after transplantation.

PMID- 20133000
TI  - The new therapeutic frontier--nuclear receptors and the liver.
AB  - A joint EASL/AASLD Monothematic Conference on 'Nuclear Receptors and Liver
      Disease' was held from February 27th to March 1st, 2009, in Vienna, Austria, to
      discuss the latest advances at the forefront of basic and clinical nuclear
      receptor research and its potential implications for liver diseases. This article
      reports the highlights of the conference and summarizes the main conclusions
      emphasizing the relevance for clinical and experimental hepatology. The
      confluence of nuclear receptors as central transcriptional regulators, acting as
      sensors and adaptors to many of the small molecules present in the intracellular
      milieu of all the cells of the liver, provides a current framework to address a
      broader physiological understanding of the liver. The next stage will be the
      design and testing of safe and effective therapeutics.

PMID- 20133001
TI  - Advanced glycation end products induce production of reactive oxygen species via
      the activation of NADPH oxidase in murine hepatic stellate cells.
AB  - BACKGROUND & AIMS: Advanced glycation end products are known to play an important
      role in the metabolic syndrome and were recently suggested to contribute to liver
      fibrosis development. However, little is known about the effect of advanced
      glycation end products on hepatic stellate cells, the major contributors to liver
      fibrosis development. We therefore studied the effect of advanced glycation end
      products on reactive oxygen species generation, a main feature for the activation
      hepatic stellate cells. METHODS: Three different types of advanced glycation end
      products were generated by BSA incubation with different substrates. The presence
      of advanced glycation end product receptors was examined by RTq-PCR,
      immunofluorescence and western blotting. Reactive oxygen species production was
      measured using DCFH-DA. RESULTS: Hepatic stellate cells express five advanced
      glycation end product receptors: Galectin-3, CD36, SR-AI, SR-BI and RAGE. All
      receptors, except SR-BI, showed up-regulation during HSC activation. All three
      advanced glycation end product types induced reactive oxygen species generation.
      DPI and NSC, a NADPH oxidase and a Rac1 inhibitor respectively, inhibited
      reactive oxygen species production. Rottlerin, a molecule often used as a
      PKCdelta inhibitor, also abrogated reactive oxygen species production. SiRNA
      mediated knockdown of p47(phox), Rac1 and PKCdelta decreased reactive oxygen
      species production induced by advanced glycation end products, establishing a
      role for these proteins in reactive oxygen species induction. CONCLUSIONS: The
      demonstration of advanced glycation end product-induced reactive oxygen species
      generation in hepatic stellate cells unveils a potential new route through which
      advanced glycation end products induce liver fibrosis in the metabolic syndrome.

PMID- 20133003
TI  - Genetic polymorphism and response to treatment in chronic hepatitis C: the future
      of personalized medicine.

PMID- 20133002
TI  - Iron uptake from plasma transferrin by a transferrin receptor 2 mutant mouse
      model of haemochromatosis.
AB  - BACKGROUND & AIMS: Hereditary haemochromatosis type 3 is caused by mutations in
      transferrin receptor (TFR) 2. TFR2 has been shown to mediate iron transport in
      vitro and regulate iron homeostasis. The aim of this study was to determine the
      role of Tfr2 in iron transport in vivo using a Tfr2 mutant mouse. METHODS: Tfr2
      mutant and wild-type mice were injected intravenously with (59)Fe-transferrin and
      tissue (59)Fe uptake was measured. Tfr1, Tfr2 and ferroportin expression was
      measured by real-time PCR and Western blot. Cellular localisation of ferroportin
      was determined by immunohistochemistry. RESULTS: Transferrin-bound iron uptake by
      the liver and spleen in Tfr2 mutant mice was reduced by 20% and 65%,
      respectively, whilst duodenal and renal uptake was unchanged compared with iron
      loaded wild-type mice. In Tfr2 mutant mice, liver Tfr2 protein was absent, whilst
      ferroportin protein was increased in non-parenchymal cells and there was a low
      level of expression in hepatocytes. Tfr1 expression was unchanged compared with
      iron-loaded wild-type mice. Splenic Tfr2 protein expression was absent whilst
      Tfr1 and ferroportin protein expression was increased in Tfr2 mutant mice
      compared with iron-loaded wild-type mice. CONCLUSIONS: A small reduction in
      hepatic transferrin-bound iron uptake in Tfr2 mutant mice suggests that Tfr2
      plays a minor role in liver iron transport and its primary role is to regulate
      iron metabolism. Increased ferroportin expression due to decreased hepcidin mRNA
      levels is likely to be responsible for impaired splenic iron uptake in Tfr2
      mutant mice.

PMID- 20133004
TI  - Harmony in liver fibrosis...

PMID- 20133005
TI  - Ablation for hepatocellular carcinoma: Is there need to have a winning technique?

PMID- 20133006
TI  - T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates
      natural killer cell suppression in chronic hepatitis B.
AB  - BACKGROUND & AIMS: T cell immunoglobulin- and mucin-domain-containing molecule-3
      (Tim-3) has been shown to influence autoimmune diseases; however, its function in
      viral infection has not been well-defined. We therefore investigated the
      expression and regulatory function of Tim-3 in natural killer (NK) cells in
      chronic Hepatitis B (CHB) infection. METHODS: Seventy-six CHB patients, 38
      healthy controls, and 18 patients with fatty liver disease (FLD) were tested for
      Tim-3 expression on peripheral blood mononuclear cells (PBMCs) and in the liver
      tissue by flow cytometry and immunohistochemical stainning. The effects of HBV
      infection on Tim-3 expression in NK cells and the roles of Tim-3 in regulation of
      NK-cell function were also studied. RESULTS: There was a significant increase of
      Tim-3 expression in PBMCs, circulating NK cells and liver infiltrating
      lymphocytes (LILs) from CHB patients compared to that of healthy controls and FLD
      patients. Increased Tim-3 expression was also detected in NK92 cells that had
      been transfected with a HBV expression vector and NK cells isolated from the
      liver of HBV transgenic mice. Importantly, blockage of Tim-3 signaling with anti
      Tim-3 antibodies or Tim-3-Fc fusion proteins resulted in an increased
      cytotoxicity for NK92 cells compared to HepG2 and HepG2.2.15 cells, as well as an
      elevated interferon-gamma (IFN-gamma) production. Similarly, enhanced
      cytotoxicity was also observed in PBMCs or NK cells from CHB patients treated
      with the Tim-3 blockade ex vivo. CONCLUSION: HBV infection can up-regulate Tim-3
      expression in NK cells, which may in turn suppress NK-cell functions in CHB
      patients.

PMID- 20133007
TI  - Analytical radiography for planar radiographic images implemented with a multi
      modal system.
AB  - A radiographic system is optimized for the contrast inherent to small animals and
      is developed for a multi-modal imaging system devised for in-vivo studies. The
      range of X-ray energies utilized (generally considered "soft X-rays") enables
      enhanced spatial resolution and superior contrast for detailed study of the mouse
      anatomy and smaller specimens. Despite the difficulties presented by the
      complicated energy spectrum of soft X-rays, relevant system calibrations for bone
      measures are described in detail and applied to the mouse. Further, long-bone
      symmetry modeling using a cylindrical projection is applied to the planar density
      image, providing convenient bone density estimates that are consistent with other
      methodologies.

PMID- 20133008
TI  - Large cell/neuroendocrine carcinoma.
AB  - Large cell neuroendocrine tumors of the lung represent a recently reclassified
      subtype of lung cancer with features of both small cell and non-small cell lung
      cancer. We review diagnostic difficulties, typical presentations, and the natural
      history of this tumor. We review treatment data, and suggest that as in more
      common types of lung cancer, multi-modality therapy may be the most promising
      course of treatment.

PMID- 20133009
TI  - Modulation of actin filament dynamics by actin-binding proteins residing in
      lamellipodia.
AB  - Lamellipodial extension depends essentially on the polymerisation cycle of actin.
      In this cellular compartment the rate and extent of actin polymerisation is
      tightly regulated by a large number of actin-binding proteins. The main
      regulators comprise proteins of the actin-depolymerising factor (ADF)/cofilin
      family, which stimulate actin cycling, but there are also minor constituents like
      gelsolin and certain variants of tropomyosin that have so far not been considered
      to be lamellipodial constituents. A number of cell lines express ADF and cofilin
      simultaneously as shown here for the fibroblastic normal rat kidney (NRK) cell
      line. Both proteins co-localise in the lamellipodial region. We furthermore
      demonstrate the presence of gelsolin in lamellipodia by immunostaining with anti
      gelsolin antibodies and transfection with EGFP-tagged gelsolin constructs. The
      presence of tropomyosins in lamellipodia has recently been reported (Hillberg et
      al., 2006. Tropomyosins are present in lamellipodia of motile cells. Eur. J. Cell
      Biol. 85, 399-409). In order to evaluate the effect of the simultaneous presence
      of ADF and cofilin together with tropomyosin and/or gelsolin on the
      polymerisation cycle of actin, we analysed their effect or combinations of these
      actin-binding proteins on the steady-state F-actin-ATPase activity in biochemical
      assays. Our results demonstrate stimulatory effects of ADF/cofilin on actin
      cycling and a further modulation of ADF/cofilin-stimulated F-actin-ATPase
      activity by gelsolin and tropomyosin in a complex manner.

PMID- 20133010
TI  - Arabidopsis cryptochrome-1 restrains lateral roots growth by inhibiting auxin
      transport.
AB  - Cryptochromes are blue-light photoreceptors that control many aspects of plant
      development. In this study, cryptochrome mutants of Arabidopsis were examined to
      assess the role of cryptchrome-1 (CRY1) in lateral roots growth. When grown in
      blue light for 12d, mutant seedlings (cry1) showed increased growth of lateral
      roots, while CRY1-overexpressing transgenic seedlings (CRY1ox) exhibited a marked
      decrease. Lateral roots growth of CRY1ox could be stimulated by auxin, but
      expression of PIN1 (efflux carrier of polar auxin transport) was strongly
      reduced. Contrary, the cry1 mutation showed the opposite effect, indicating that
      blue light and the auxin-signaling pathway interact in lateral roots growth of
      Arabidopsis. The free IAA content in CRY1ox roots was half of that in wild type
      and cry1 mutant roots. Moreover, the content of flavonoids (quercetin,
      kaempferol, isorhamnetin), which act as endogenous negative regulators of auxin
      transport, increased in CRY1ox seedlings. Taken together, these results suggest
      that Arabidopsis CRY1 restrains lateral roots growth by inhibiting auxin
      transport.

PMID- 20133011
TI  - [Limbal-conjunctival autograft in pterygium surgery].
AB  - INTRODUCTION: The aim of this study was to estimate the efficacy of limbal
      conjunctival autograft in the treatment of pterygium. MATERIAL AND METHODS: We
      conducted a retrospective study including 15 patients (16 eyes) operated on for
      pterygium by limbal-conjunctival autograft. The examination included the search
      for risk factors and visual acuity, as well as corneal astigmatism and pterygium
      measurement. The follow-up included an examination at day 8, 1 month, and 3
      months and assessed the integration of the transplant on the eye's surface, the
      aesthetic aspect, and recurrence. We describe the patients' characteristics,
      visual acuity, and astigmatism before and after surgery. RESULTS: The mean age of
      the patients was 56 years (range, 31-81 years). Before surgery, irritative signs
      and astigmatism, were found in 37% and impaired visual acuity in 81%. The mean
      duration of the follow-up after surgery was 19 months. Visual acuity and
      astigmatism improved in 56% of our patients. All transplants and harvest sites
      had a satisfactory macroscopic aspect. However, one patient suffered from a
      corneal invasion by fibrovascular tissue, 7 months postoperatively, which
      remained stable at the end of follow-up. DISCUSSION/CONCLUSION: In our study, the
      limbal-conjunctival autograft was a safe and effective surgical treatment with a
      very low recurrence rate at long-term follow-up.

PMID- 20133012
TI  - Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two
      placebo-controlled studies of daily application to the face and balding scalp for
      two 3-week cycles.
AB  - BACKGROUND: Imiquimod 5% cream is approved as a 16-week regimen for the treatment
      of actinic keratoses involving a 25-cm(2) area of skin. OBJECTIVE: We sought to
      evaluate imiquimod 2.5% and 3.75% creams for short-course treatment of the entire
      face and scalp. METHODS: In two identical studies, adults with 5 to 20 lesions
      were randomized to placebo, or imiquimod 2.5% or 3.75% cream (1:1:1). Up to two
      packets (250 mg each) were applied per dose once daily for two 3-week treatment
      cycles, with a 3-week, no-treatment interval. Efficacy was assessed at 8 weeks
      posttreatment. RESULTS: In all, 490 subjects were randomized to placebo, or
      imiquimod 2.5% or 3.75% cream. Median baseline lesion counts for the treatment
      groups were 9 to 10. Complete and partial clearance rates were 5.5% and 12.8% for
      placebo, 25.0% and 42.7% for imiquimod 2.5%, and 34.0% and 53.7% for imiquimod
      3.75% (P < .001, each imiquimod vs placebo; P = .034, 3.75% vs 2.5% for partial
      clearance). Median reductions from baseline in lesion count were 23.6%, 66.7%,
      and 80.0% for the placebo, imiquimod 2.5%, and imiquimod 3.75% groups,
      respectively (P < .001 each imiquimod vs placebo). There were few treatment
      related discontinuations. Temporary treatment interruption (rest) rates were 0%,
      17.1%, and 27.2% for the placebo, imiquimod 2.5%, and imiquimod 3.75%,
      respectively. LIMITATIONS: Local effects of imiquimod, including erythema, may
      have led to investigator and subject bias. CONCLUSIONS: Both imiquimod 2.5% and
      3.75% creams were more effective than placebo and had an acceptable safety
      profile when administered daily as a 3-week on/off/on regimen.

PMID- 20133013
TI  - Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two
      placebo-controlled studies of daily application to the face and balding scalp for
      two 2-week cycles.
AB  - BACKGROUND: The approved imiquimod 5% cream regimen for treating actinic
      keratoses requires a long treatment time and is limited to a small area of skin.
      OBJECTIVE: We sought to evaluate imiquimod 2.5% and 3.75% for short-course
      treatment of the full face or balding scalp. METHODS: In two identical studies,
      adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or
      imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose
      once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval
      between cycles. Efficacy was assessed at 8 weeks posttreatment. RESULTS: A total
      of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete
      and partial clearance (> or =75% lesion reduction) rates were 6.3% and 22.6% for
      placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod
      3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for
      partial clearance). Median reductions from baseline in lesion counts were 25.0%
      for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001,
      each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related
      discontinuations. Patient rest period rates were 0% for placebo, 6.9% for
      imiquimod 2.5%, and 10.6% for imiquimod 3.75%. LIMITATIONS: Local pharmacologic
      effects of imiquimod, including erythema, may have limited concealment of
      treatment assignment in some patients. CONCLUSIONS: Both imiquimod 2.5% and 3.75%
      creams were more effective than placebo and were well tolerated when administered
      daily as a 2-week on/off/on regimen to treat actinic keratoses.

PMID- 20133014
TI  - Believing is seeing.

PMID- 20133015
TI  - Early neuronal dysfunction by amyloid beta oligomers depends on activation of
      NR2B-containing NMDA receptors.
AB  - Several studies indicate that NMDA receptor signaling is involved in Abeta
      oligomer-mediated impairment of neuronal function and morphology. Utilizing
      primary neuronal cell culture and hippocampal slices from rat and mouse, we found
      that Abeta oligomer administration readily impairs long-term potentiation,
      reduces baseline synaptic transmission, decreases neuronal spontaneous network
      activity and induces retraction of synaptic contacts long before major cytotoxic
      effects are visible. Interestingly, all these effects can be blocked with the
      NR2B-containing NMDA-receptor antagonist ifenprodil or Ro 25-6981 suggesting that
      activation of downstream effectors of these receptors is involved in early
      detrimental actions of Abeta oligomers. In line we found that Jacob, a messenger
      that can couple extrasynaptic NMDA-receptor activity to CREB dephosphorylation,
      accumulates in the nucleus after Abeta oligomer administration and that the
      nuclear accumulation of Jacob can be blocked by a simultaneous application of
      ifenprodil. We conclude that Abeta oligomers induce early neuronal dysfunction
      mainly by activation of NR2B-containing NMDA-receptors.

PMID- 20133016
TI  - Association of AICD and Fe65 with Hirano bodies reduces transcriptional
      activation and initiation of apoptosis.
AB  - Hirano bodies are cytoplasmic inclusions predominantly found in the central
      nervous system associated with various conditions including aging and Alzheimer's
      disease (AD). Since most studies of Hirano bodies have been performed in post
      mortem samples, the physiological roles of Hirano bodies have not been
      investigated. Astrocytoma H4 cells were employed to test the hypothesis that
      Hirano bodies interact with and modulate signaling by the C-terminal fragment of
      amyloid-beta precursor protein (AICD). We demonstrated by immunofluorescence and
      immunoprecipitation that model Hirano bodies accumulate AICD. Since stimulation
      of transcription by AICD is dependent on its interaction with the nuclear adaptor
      protein Fe65, we examined localization of Fe65, and employed a dual luciferase
      reporter assay to test the effects of Hirano bodies on AICD- and Fe65-dependent
      modulation of gene expression. We find that both AICD and Fe65 are co-localized
      in model Hirano bodies. Model Hirano bodies also down-regulate both AICD
      dependent apoptosis and AICD- and Fe65-dependent transcriptional activity. Thus,
      association of AICD and Fe65 with Hirano bodies impedes their function in
      promoting apoptosis and modulating transcription.

PMID- 20133018
TI  - [Symptom profile in gastroesophageal reflux disease in untreated patients and
      those with persistent symptoms despite treatment].
AB  - AIM: 1. To analyze the symptom profile of gastroesophageal reflux disease (GERD)
      with typical clinical manifestations (heartburn and/or regurgitation); 2. to
      compare untreated patients with those with persistent symptoms despite treatment;
      3. to evaluate severity according to physicians' and patients' opinions; and 4.
      to determine the diagnostic and therapeutic approaches used. METHODS: We
      performed a prospective, observational, cross-sectional study under conditions of
      standard clinical practice. RESULTS: A total of 2356 patients were included.
      Dyspeptic symptoms were highly frequent (close to 90% in both groups) and
      supraesophageal symptoms were also common (50-60%). Patients with persistent
      symptoms despite treatment were older, and had more supraesophageal symptoms; in
      addition, the typical supraesophageal and dyspeptic symptoms of GERD were more
      severe in these patients. Severity evaluations by patients and doctors were
      concordant but patients considered severity to be greater. Older age was a risk
      factor for supraesophageal symptoms, female gender for dyspeptic symptoms and
      body mass index for greater severity of GERD symptoms. Endoscopy was requested in
      about 60% of the patients. Diet counseling was advised in most patients and
      postural recommendations were made in more than half. Proton pump inhibitors were
      prescribed in almost all patients, and were associated with prokinetics and/or
      antacids in many patients. CONCLUSIONS: Dyspeptic symptoms should not be
      considered as independent of GERD, and typical and atypical symptoms are
      associated in 50% of patients. Gastroenterologists follow clinical practice
      guidelines fairly closely but diagnostic procedures seem to be overindicated.

PMID- 20133017
TI  - Phosphorylated tau 231, memory decline and medial temporal atrophy in normal
      elders.
AB  - Little is known whether cerebrospinal fluid (CSF) biomarkers of Alzheimer's
      disease (AD) can predict both memory decline and associated longitudinal medial
      temporal lobe (MTL) gray matter (GM) reductions in cognitively healthy
      individuals. Fifty-seven normal elderly subjects received comprehensive
      evaluation at baseline and 2 years later. The baseline phosphorylated tau(231) (p
      tau(231)), total tau, the amyloid beta (Abeta) Abeta42/Abeta40, t-tau/Abeta42 and
      p-tau(231)/Abeta42 ratios were examined as predictors of memory change and
      reductions in the global and MTL GM, determined from T1-weighted MRI. Twenty out
      of 57 participants experienced reduced memory performance at follow-up. The group
      with decreased memory performance showed higher baseline p-tau(231) (Z=-2.2,
      p=0.03), lower Abeta42/Abeta40 (t=-2.2 [55], p=0.04) and greater longitudinal MTL
      GM reductions (t([52])=-2.70, p=0.01). Higher baseline p-tau(231) was also
      associated with the absolute decrease in memory scores (rho=-0.30, p=0.02) and
      with longitudinal MTL GM reduction (F([2,52])=4.4, p=0.04, age corrected). Our
      results indicate that in normal individuals, elevated p-tau(231), a marker of
      neurofibrillary pathology is related to both a decrease in declarative memory and
      progressive atrophy of the MTL, suggesting its diagnostic potential in
      preclinical stage.

PMID- 20133019
TI  - [What do general practitioners think about evidenced-based medicine? A study with
      focus groups].
AB  - OBJECTIVE: To examine the attitudes of a sample of General Practitioners (GPs)
      towards Evidenced-Based Medicine (EBM) and its use and the obstacles to put into
      practice in Primary Care (PC). DESIGN: Qualitative study using Focus Groups (FG).
      SETTING: Primary Care in the Autonomous Community of Murcia, Spain, January-June
      2007. PARTICIPANTS: GPs with a clinical practice in PC in the Murcian Health
      Service. METHOD: Two FG (with/without previous training in EBM). Using
      intentional sampling, 19 GPs were selected from PC professionals. The discussions
      were recorded on video and transcribed literally. The discussions were then,
      segmented, categorised and interpreted. RESULTS: Attitudes: EBM is useful, it
      helps to reduce variation in clinical practice and decreases uncertainty. Great
      importance is given to clinical experience and the role of the Pharmaceutical
      Industry and the Health Administration may have in its promotion is viewed with
      suspicion. Use: Its use is still limited. To consult with colleagues continues to
      be the main source of information. Obstacles: The major difficulties identified
      were the limited time it has been available, lack of experience and the language.
      CONCLUSIONS: Although GPs show a positive attitude towards EBM, there are still a
      few who recognise the use of consultation. The main limitation identified was
      lack of time in the clinic due to excessive pressure of care work. To increase
      its use, they proposed, more training activities, motivation by an appropriate
      process and reorganisation of their care work.

PMID- 20133020
TI  - [Experience with 123I-Iodobenzamide in the differential diagnosis of Parkinson's
      disease and Parkinson-plus disease].
AB  - OBJECTIVE: To perform a descriptive analysis of the clinical and diagnostic
      implications of (123)I-IBZM SPECT in the patients studied in our center for
      movement disorders suggestive of Parkinson-Plus Disease (PP). SUBJECTS AND
      METHODS: (123)I-IBZM SPECT was performed in 46 patients referred from the
      movement disorders consultation due to suspicion of PP. According to their
      symptoms, they were distributed into 3 groups: 35 patients had atypical symptoms
      (AS) for Parkinson's Disease, 2 showed no response to standard therapy (NR) and 9
      presented both factors (AS, NR). The results of SPECT were only assessed
      qualitatively. RESULTS: The (123)I-IBZM supported the diagnosis of PP in
      15(42.9%) out of the 35 patients with AS. The (123)I-IBZM was pathological in one
      of the two NR patients. Regarding the third group of patients (AS+NR), the (123)I
      IBZM was pathological in 6 cases (66.7%). In 95.7% of our sample (44 patients),
      AS with or without NR was the main factor leading to suspicion of PP and the
      (123)I-IBZM was altered in only 47.7% (22 patients). Of these 22 cases, the final
      diagnosis was PP (with high positive predictive value) in 20(91%). CONCLUSION:
      The study with (123)I-IBZM is useful in the clinical practice because it provides
      objective diagnostic information with implications for the treatment and
      prognosis of patients with suspicion of PP.

PMID- 20133021
TI  - Modulation of doxorubicin activity in cancer cells by conjugation with fatty acyl
      and terpenyl hydrazones.
AB  - Doxorubicin N-acylhydrazones derived from saturated, unsaturated and terpene
      terminated fatty acids were tested for anticancer activity in cells of human HL
      60 leukaemia, 518A2 melanoma, MCF-7/Topo breast and KB-V1/Vbl cervix carcinomas.
      In the latter, the N-heptadecanoyl hydrazone was more cytotoxic than its
      unsaturated C18-fatty acyl analogues and even three times more than doxorubicin.
      The (menthoxycarbonyl)undecanoyl hydrazone was twice as active as doxorubicin in
      these multidrug resistant KB-V1/Vbl and in the 518A2 cells and also more
      efficacious in KB-V1 and MCF-7 cells that had been desensitised for doxorubicin.
      All hydrazones induced apoptosis albeit by slightly different mechanisms. While
      apoptosis induction by the menthoxymalonyl hydrazone was characterized by an
      upfront increase in caspase-8 activity, all other hydrazones elicited a hike in
      caspase-9 activity. Treatment of HL-60 and 518A2 cells with doxorubicin or its
      heptadecanoyl, linolenoyl, (menthoxycarbonyl)undecanoyl or menthoxymalonyl
      hydrazones also led to diverging increases of the ratio of bax to bcl-2 mRNA
      expression, of reactive oxygen species and of mitochondrial membrane damage.

PMID- 20133022
TI  - Synthesis, pharmacological activity and comparative QSAR modeling of 1,5-N,N'
      substituted-2-(substituted naphthalenesulphonyl) glutamamides as possible
      anticancer agents.
AB  - Based on our earlier QSAR study, a series of 1, 5-N,N'-substituted-2-(substituted
      naphthalenesulphonyl) glutamamides were synthesized as possible anticancer
      agents. Anticancer activities of these synthesized compounds were evaluated in
      vivo on Swiss Albino mice against Ehrlich Ascites Carcinoma (EAC) cells where
      inhibitions of tumor cell and tumor weight were considered as biological activity
      parameters. A comparative QSAR study was done with a set of descriptors and
      logarithm of tumor cell inhibition. The result shows the importance of
      topological parameters like ETSA and RTSA indices as well as electronic parameter
      like Wang-Ford charges of different atoms. Electrophilic attack at atom number 5
      and increased number of chlorine atom may be favorable whereas presence of
      methoxy group at the atom number 8 in naphthalene ring may be detrimental to the
      activity.

PMID- 20133023
TI  - New Cu(II), Co(II), Ni(II) complexes with aroyl-hydrazone based ligand.
      Synthesis, spectroscopic characterization and in vitro antibacterial evaluation.
AB  - A new aroyl-hydrazone, N-(2-pyridinecarbaldehyde)-N'-[4-(4-chloro-phenylsulfonyl)
      benzoyl]-hydrazone (L) and its Cu(II), Co(II) and Ni(II) complexes have been
      prepared. The structure of these compounds has been investigated by using
      elemental analysis, magnetic susceptibility, molar conductance, thermal and
      spectral (IR, UV, NMR, LC-MS, EPR) measurements. The semi-empirical method MM2,
      LC-ESI-MS, NMR and IR spectra indicate that the ligand behaves as mononegative
      bidentate/tridentate with NO/NON donor sequence in E isomeric form towards the
      metal ions. The magnetic and spectral data indicate a square-planar geometry for
      Ni2+ complex and an octahedral or pseudo-tetrahedral geometry for Co2+ and Cu2+
      complexes. Bacterial activity of acyl-hydrazone (L) and its complexes were
      studied against gram-positive bacteria: Staphylococcus aureus, Bacillus subtilis
      and gram-negative bacteria: Pseudomonas aeruginosa, Escherichia coli by using
      minimum inhibitory concentrations (MICs) method.

PMID- 20133024
TI  - In-vivo analgesic and anti-inflammatory activities of newly synthesized
      benzimidazole derivatives.
AB  - A series of 2-methylaminobenzimidazole derivatives (1-11) were synthesized by the
      reaction of 2-(chloromethyl)-1H-benzimidazole derivatives with primary aromatic
      amines. All these compounds were characterized by IR, 1H NMR, 13C NMR, GC-MS and
      elemental analysis. The newly synthesized compounds were screened for analgesic
      and anti-inflammatory activities on acetic acid induced writhing in mice and
      carrageenan induced paw oedema in rats. Compounds (7) and (2) showed a potent
      analgesic (89% at 100 mg/kg b.w) and anti-inflammatory (100% at 100 mg/kg b.w)
      activities compared with standard drug Nimesulide (100% at 50 mg/kg b.w)
      respectively. The other compounds showed good analgesic and anti-inflammatory
      activities.

PMID- 20133025
TI  - Synthesis and biological activity of n-butylphthalide derivatives.
AB  - A series of n-butylphthalide derivatives were designed and synthesized. The in
      vitro activities of these compounds were evaluated by a resting tension of
      isolated rat thoracic aorta ring assay. Compounds 4g and 4i were found to be more
      active than n-butylphthalide.

PMID- 20133026
TI  - Reaction mechanisms of allicin and allyl-mixed disulfides with proteins and small
      thiol molecules.
AB  - Allylsulfides from garlic are chemopreventive agents. Entering cells they are
      expected to initially interact with glutathione. Accordingly, reaction mechanisms
      of the product, S-allylthio-glutathione, with model proteins and thiols were
      analyzed in cell free systems. With glutathionyl, cysteinyl or captopril
      representing S-allyl aliphatic adducts, the reaction with sulfhydryl groups
      resulted in mixed disulfide mixtures, formed by both, S-allyl and aliphatic
      moieties. To improve conventional prodrug treatment of blood pressure, cancer and
      intestinal inflammation S-allylthio prodrugs, such as S-allylthio-6
      mercaptopurine and S-allylthio-captopril were synthesized. Synergistic activities
      of the 2 constituents, as well as increased cell permeability allow for efficient
      in vivo activity. Upon reaction of these derivatives with glutathione, S
      allylthio-glutathione is formed, while 6-mercaptopurine is the leaving group.
      Excess cellular glutathione enables several cycles of sulfhydryl-disulfide
      exchange reactions to occur, extending the hybrid drug's pharmacodynamics.

PMID- 20133027
TI  - The bioisosteric similarity of the tetrazole and carboxylate anions: clues from
      the topologies of the electrostatic potential and of the electron density.
AB  - There is a need for an a priori method with which to demonstrate the physical
      similarities between non-classical bioisosteres. In this study we explore the
      utility of the electron density and the electrostatic potential as the basis for
      a systematic investigation of the physical and chemical similarities between
      bioisosteres. The tetrazole and carboxylate bioisosteric pair is used as an
      illustrative example. It is shown that tetrazole and carboxylate anions give rise
      to electrostatic potentials (ESP) that exhibit a remarkable local similarity in
      the disposition of four coplanar local minima at positions consistent with lone
      pairs. The similarity of the disposition of these ESP minima generated by the two
      bioisosteres is in sharp contrast with their differences in the number and types
      of atoms, their nuclear geometrical arrangements, their total volumes, their
      partial charges, and their electron populations. The topology and geometrical
      disposition of these minima are shown to be independent of the capping group used
      in the model, and thus an inherent property of this bioisosteric pair. A model of
      the receptor region responsible for binding to either of these bioisosteres is
      proposed on the basis of an electrostatic "lock-and-key".

PMID- 20133028
TI  - Pharmacophore-based 3D QSAR studies on a series of high affinity 5-HT1A receptor
      ligands.
AB  - 5-HT(1A) receptor antagonists have been employed to treat depression, but the
      lack of structural information on this receptor hampers the design of specific
      and selective ligands. In this study, we have performed CoMFA studies on a
      training set of arylpiperazines (high affinity 5-HT(1A) receptor ligands) and to
      produce an effective alignment of the data set, a pharmacophore model was
      produced using Galahad. A statistically significant model was obtained,
      indicating a good internal consistency and predictive ability for untested
      compounds. The information gathered from our receptor-independent pharmacophore
      hypothesis is in good agreement with results from independent studies using
      different approaches. Therefore, this work provides important insights on the
      chemical and structural basis involved in the molecular recognition of these
      compounds.

PMID- 20133029
TI  - The relationship between nursing students' mathematics ability and their
      performance in a drug calculation test.
AB  - Nurses and nursing students need good mathematics skills to do drug calculations
      correctly. As part of their undergraduate education, Norwegian nursing students
      must take a drug calculation test, obtaining no errors in the results. In spite
      of drug calculation tests, many adverse events occur, leading to a focus on drug
      administration skills both during students' courses and afterwards. Adverse
      events in drug administration can be related to poor mathematics skills
      education. The purpose of this study was to investigate the relationship between
      students' mathematics experiences in school (primary, secondary and high school)
      and their beliefs about being able to master the drug calculation test. A
      questionnaire was given to 116 first-year Bachelor of Nursing students. Those
      students who assessed their mathematics knowledge as poor found the requirement
      to obtain no errors in the drug calculation test more stressful than students who
      judged their mathematics knowledge as good. The youngest students were most
      likely to find the test requirement stressful. Teachers in high school had the
      most positive influence on mathematics interest, followed by teachers in
      secondary and primary school.

PMID- 20133030
TI  - Patellar tendon repair with hamstring autograft: a cadaveric analysis.
AB  - BACKGROUND: Rupture of the patellar tendon requires surgical repair to restore
      function of the knee. The most accepted repair technique utilizes running locking
      non-absorbable sutures secured to the patella through three drill holes.
      Complications with this repair technique include rerupture, knee stiffness, and
      extensor lag caused by gap formation at the site of repair. Some surgeons have
      suggested augmenting the standard repair with local autograft tendon to avoid
      these complications. It was hypothesized that using a repair technique that
      included augmentation of the repair with autograft tendons would decrease the gap
      formation at the repair site under cyclic loading conditions. METHODS: In this
      experiment, eight specimens were used to analyze two methods of patellar tendon
      repair: hamstrings autograft augmentation and a standard repair using three
      vertical bone tunnels in the patella. Each specimen was then extended with a 2.2
      kg weight on the tibia at 0.25 Hz to simulate early motion after surgery. The gap
      formed at the repair site was then measured at 1, 10, 100, and 250 cycles and
      both techniques confidence interval compared using a Wilcoxon signed rank test.
      FINDINGS: The mean gap formation for the standard repair after one cycle was 8.9
      mm (SD 2.4) and for the augmented repair was 3.6mm (SD 0.9). At 250 cycles the
      mean gap formed for the standard repair was 13.2mm (SD 1.9) and the mean gap for
      the augmented repair was 7.2mm (SD 0.9). All gaps for all cycles analyzed had an
      88% confidence interval for significance using a Wilcoxon signed rank test.
      INTERPRETATION: The biomechanical results of this study show statistical trend
      toward decrease gap formation with an augmented tendon at the repair site under a
      simulated dynamic knee motion.

PMID- 20133031
TI  - Advances in understanding ozone impact on forest trees: messages from novel
      phytotron and free-air fumigation studies.
AB  - Recent evidence from novel phytotron and free-air ozone (O3) fumigation
      experiments in Europe and America on forest tree species is highlighted in
      relation to previous chamber studies. Differences in O3 sensitivity between
      pioneer and climax species are examined and viewed for trees growing at the harsh
      alpine timberline ecotone. As O3 apparently counteracts positive effects of
      elevated CO2 and mitigates productivity increases, response is governed by
      genotype, competitors, and ontogeny rather than species per se. Complexity in O3
      responsiveness increased under the influence of pathogens and herbivores. The new
      evidence does not conflict in principle with previous findings that, however,
      pointed to a low ecological significance. This new knowledge on trees' O3
      responsiveness beyond the juvenile stage in plantations and forests nevertheless
      implies limited predictability due to complexity in biotic and abiotic
      interactions. Unravelling underlying mechanisms is mandatory for assessing O3
      risks as an important component of climate change scenarios.

PMID- 20133032
TI  - Prevention of chloridazon and metribuzin pollution using lignin-based
      formulations.
AB  - The herbicides chloridazon and metribuzin, identified as groundwater pollutants,
      were incorporated in lignin-based granules with different sizes to obtain
      controlled release formulations (CRFs) and reduce water pollution risk. Kinetics
      release tests in water and soil showed that the release rate of both from CRFs
      diminished in comparison to technical products. A linear correlation was obtained
      between the time taken for 50% of the active ingredient to be released (T(50))
      into water and granule size of the CRFs. Besides, a linear correlation was
      reached between T(50) values in water and soil. Mobility experiments carried out
      in calcareous soil show that the use of lignin-based CRFs reduces the presence of
      both herbicides in the leachate compared to the technical grade products. The set
      of experiments developed in this research can be useful to design, prepare and
      evaluate formulations with CR properties which can reduce the pollution derived
      from the use of herbicides.

PMID- 20133033
TI  - Systematic review and meta-analysis of exercise tolerance and physical
      functioning in dialysis patients treated with erythropoiesis-stimulating agents.
AB  - BACKGROUND: The role of erythropoiesis-stimulating agents (ESAs) in treating the
      anemia of chronic kidney disease has been reevaluated in view of recent studies
      suggesting that the use of these agents may be associated with increased
      morbidity and mortality. This potential increased risk needs to be weighed
      against the potential benefit of ESAs in improving various aspects of health
      related quality of life, in particular, exercise tolerance and physical
      functioning. STUDY DESIGN: A systematic review and meta-analysis of exercise
      tolerance and physical functioning. SETTING & PARTICIPANTS: Adults on maintenance
      dialysis therapy. SELECTION CRITERIA FOR STUDIES: Outcomes measured before and
      after ESA treatment were required. Studies of physical function were required to
      include at least 25 participants. INTERVENTION: Treatment with any ESA. OUTCOMES:
      Exercise tolerance measured using VO(2peak) (oxygen consumption per minute at the
      peak workload during the test), duration of exercise, or 6-minute walk distance
      or physical functioning assessed using > or = 1 patient- or clinician-reported
      outcome measure that included a physical function domain. RESULTS: 28 articles
      met criteria for inclusion for evaluation of exercise tolerance, and 14 articles,
      for physical function. Meta-analysis showed a 23.8% increase in VO(2peak) from
      before to after erythropoietin therapy initiation (15 studies) and a
      nonsignificant 8.2% increase comparing a higher with a lower hemoglobin target (3
      studies). For physical functioning, 4 studies met criteria for inclusion in the
      meta-analysis: there was a 10.5% increase in Karnofsky score from before to after
      erythropoietin therapy initiation. LIMITATIONS: Many studies of exercise
      tolerance did not include control groups. A wide variety of instruments was used
      to assess physical function. CONCLUSIONS: Partial correction of anemia through
      ESA treatment has a consistent and positive impact on VO(2peak). ESA treatment
      improves patient- and clinician-assessed physical functioning.

PMID- 20133034
TI  - Groundwater vulnerability assessment for the Banyas Catchment of the Syrian
      coastal area using GIS and the RISKE method.
AB  - Vulnerability assessment to delineate areas that are more susceptible to
      contamination from anthropogenic sources has become an important element for
      sensible resource management and landuse planning. This contribution aims at
      estimating aquifer vulnerability by applying the RISKE model in Banyas Catchment
      Area (BCA), Tartous Prefecture, west Syria. An additional objective is to
      demonstrate the combined use of the RISKE model and a geographical information
      system (GIS) as an effective method for groundwater pollution risk assessment.
      The RISKE model uses five environmental parameters (Rock of aquifer media,
      Infiltration, Soil media, Karst, and Epikarst) to characterize the hydro
      geological setting and evaluate aquifer vulnerability. The elevated eastern and
      low western part of the study area was dominated by high vulnerability classes,
      while the middle part was characterized by moderate vulnerability classes. Based
      on the vulnerability analysis, it was found that 2% and 39% of BCA is under low
      and high vulnerability to groundwater contamination, respectively, while more
      than 52% and 5% of the area of BCA can be designated as an area of moderate and
      very high vulnerability to groundwater contamination, respectively. The GIS
      technique has provided an efficient environment for analyses and high
      capabilities of handling a large amount of spatial data.

PMID- 20133035
TI  - Effects of nonlinear propagation in ultrasound contrast agent imaging.
AB  - This paper investigates two types of nonlinear propagation and their effects on
      image intensity and contrast-to-tissue ratio (CTR) in contrast ultrasound images.
      Previous studies have shown that nonlinear propagation can occur when ultrasound
      travels through tissue and microbubble clouds, making tissue farther down the
      acoustic path appear brighter in pulse inversion (PI) images, thus reducing CTR.
      In this study, the effect of nonlinear propagation through tissue or microbubbles
      on PI image intensity and CTR are compared at low mechanical index. A combination
      of simulation and experiment with SonoVue microbubbles were performed using a
      microbubble dynamics model, a laboratory ultrasound system and a clinical
      prototype scanner. The results show that, close to the bubble resonance
      frequency, nonlinear propagation through a bubble cloud of a few centimeter
      thickness with a modest concentration (1:10000 dilution of SonoVue microbubbles)
      is much more significant than through tissue-mimicking material. Consequently,
      CTR in regions distal to the imaging probe is greatly reduced for nonlinear
      propagation through the bubble cloud, with as much as a 12-dB reduction compared
      with nonlinear propagation through tissue-mimicking material. Both types of
      nonlinear propagation cause only a small change in bubble PI signals at the
      bubble resonance frequency. When the driving frequency increases beyond bubble
      resonance, nonlinear propagation through bubbles is greatly reduced in absolute
      values. However because of a greater reduction in nonlinear scattering from
      bubbles at higher frequencies, the corresponding CTR is much lower than that at
      bubble resonance frequency.

PMID- 20133036
TI  - An automatic angle tracking procedure for feasible vector Doppler blood velocity
      measurements.
AB  - Two-dimensional angle-independent blood velocity estimates typically combine the
      Doppler frequencies independently measured by two ultrasound beams with known
      interbeam angle. A different dual-beam approach was recently introduced in which
      one (reference) beam is used to identify the flow direction, and the second
      (measuring) beam directly estimates the true flow velocity at known beam-flow
      angle. In this paper, we present a procedure to automatically steer the two beams
      along optimal orientations so that the velocity magnitude can be measured. The
      operator only takes care of locating the Doppler sample volume in the region of
      interest and, through the extraction of appropriate parameters from the Doppler
      spectrum, the reference beam is automatically steered toward right orientation to
      the flow. The velocity magnitude is thus estimated by the measuring beam, which
      is automatically oriented with respect to the (known) flow direction at a
      suitable Doppler angle. The implementation of the new angle tracking method in
      the ULtrasound Advanced Open Platform (ULA-OP), connected to a linear array
      transducer, is reported. A series of experiments shows that the proposed method
      rapidly locks the flow direction and measures the velocity magnitude with low
      variability for a large range of initial probe orientations. In vitro tests
      conducted in both steady and pulsatile flow conditions produced coefficients of
      variability (CV) below 2.3% and 8.3%, respectively. The peak systolic velocities
      have also been measured in the common carotid arteries of 13 volunteers, with
      mean CV of 7%.

PMID- 20133037
TI  - A new visually evoked cerebral blood flow response analysis using a low-frequency
      estimation.
AB  - Transcranial Doppler (TCD) has been widely used to monitor cerebral blood flow
      velocity (BFV) during the performance of cognitive tasks compared with repose
      periods. Although one of its main advantages is its high temporal resolution,
      only some of the previous functional TCD studies have focused on the analysis of
      the temporal evolution of the BFV signal and none of them has performed a
      spectral analysis of the signal. In this study, maximum BFV data in both
      posterior cerebral arteries was monitored during a visual perception task (10
      cycles of alternating darkness and illumination) for 23 subjects. A peak was
      located in the low-frequency band of the spectrum of the maximum BFV of each
      subject both during visual stimulation and repose periods. The frequency of this
      peak was in the range between 0.037 and 0.098Hz, depending on the subject, the
      vessel and the experimental condition. The component of the signal at this
      frequency, which is associated with the slow variations caused by the visual
      stimuli, was estimated. That way, the variations in BFV caused by the
      experimental stimuli were isolated from the variations caused by other factors.
      This low-frequency estimation signal was used to obtain parameters about the
      temporal evolution and the magnitude variations of the BFV in a reliable way,
      thus, characterizing the neurovascular coupling of the participants.

PMID- 20133038
TI  - Ultrasonic microbubble-mediated gene delivery causes phenotypic changes of human
      aortic endothelial cells.
AB  - Ultrasound, in combination with microbubbles, serves as a feasible nonviral
      method in vascular gene delivery. However, the effects of ultrasonic microbubble
      transfection (UMT) on vascular endothelial cells remained unclear. We therefore
      investigated whether UMT itself causes phenotypic changes of the human aortic
      endothelial cells (HAEC) in vitro. HAEC were cultured with solution containing
      luciferase reporter gene and microbubbles followed by exposure to ultrasound of
      selected parameters. Thereafter, the proliferation and migration activities of
      HAEC were investigated. Real-time RT-PCR and/or western blotting were performed
      to assess expression profile of HAEC, including growth-related factors (vascular
      endothelial growth factor, fins-like tyrosine kinase-1 [Flt-1] and kinase insert
      domain-containing receptor [KDR]), coagulatory factor (von Willebrand factor),
      vasodilatory enzyme (endothelial nitric oxide synthase), gap junctional protein
      connexin43 and adhesion molecules (P-selectin, intercellular adhesion molecule 1
      and vascular cell adhesion molecule 1). The results showed that in conditions
      where UMT lead to expression of luciferase, proliferation capacity is enhanced
      (p<0.001), partly attributable to the effect of ultrasound (p<0.05), after
      excluding the effect of contact inhibition. In addition, the expression of KDR
      and Flt-1 were found increased at either the mRNA level, protein level, or both
      (p<0.05). Other markers did not have significant changes (all p>0.2). Similarly,
      the migration capacity was minimally changed (p>0.3). In conclusion, UMT causes
      phenotypic changes of HAEC by enhancing proliferation and upregulating KDR and
      Flt-1, while possesses no obvious adverse effect on viable transfected cells.
      Further investigation is required to clarify the impact of these changes by UMT
      in vivo.

PMID- 20133039
TI  - Sonoporation mediated immunogene therapy of solid tumors.
AB  - Development of gene-based therapies for the treatment of inherited and acquired
      diseases, including cancer, has seen renewed interest in the use of nonviral
      vectors coupled to physical delivery modalities. Low-frequency ultrasound (US),
      with a well-established record in a clinical setting, has the potential to
      deliver DNA efficiently, accurately and safely. Optimal in vivo parameters for US
      mediated delivery of naked plasmid DNA were established using the firefly
      luciferase reporter gene construct. Optimized parameters were used to administer
      a therapeutic gene construct, coding for granulocyte-macrophage colony
      stimulating factor (GM-CSF) and B7-1 costimulatory molecule, to growing murine
      fibrosarcoma tumors. Tumor progression and animal survival was monitored
      throughout the study and the efficacy of the US-mediated gene therapy determined
      and compared with an electroporation-based approach. Optimal parameters for US
      mediated delivery of plasmid DNA to tumors were deduced to be 1.0 W/cm(2) at 20%
      duty cycle for 5 min (60 J/cm(2)). In vivo US-mediated gene therapy resulted in a
      55% cure rate in tumor-bearing animals. The immunological response invoked was
      cell mediated, conferring resistance against re-challenge and resistance to tumor
      challenge after transfer of splenocytes to naive animals. US treatment was
      noninjurious to treated tissue, whereas therapeutic efficacy was comparable to an
      electroporation-based approach. US-mediated delivery of an immune-gene construct
      to growing tumors was therapeutically effective. Sonoporation has the potential
      to be a major factor in the development of nonviral gene delivery approaches.

PMID- 20133040
TI  - Cavitation properties of block copolymer stabilized phase-shift nanoemulsions
      used as drug carriers.
AB  - Cavitation properties of block copolymer stabilized perfluoropentane
      nanoemulsions have been investigated. The nanoemulsions were stabilized by two
      biodegradable amphiphilic block copolymers differing in the structure of the
      hydrophobic block, poly(ethylene oxide)-co-poly(L-lactide) (PEG-PLLA) and
      poly(ethylene oxide)-co-polycaprolactone (PEG-PCL). Cavitation parameters were
      measured in liquid emulsions and gels as a function of ultrasound pressure for
      unfocused or focused 1-MHz ultrasound. Acoustic droplet vaporization preceded
      generation of acoustic cavitation in liquid matrices and gels. Both stable and
      inertial cavitation was observed for focused ultrasound while only stable
      cavitation was observed for unfocused ultrasound.

PMID- 20133041
TI  - An analysis of the origin of differences between measured and simulated fields
      produced by a 15-element ultrasound phased array.
AB  - Modeling provides an attractive approach for the design of phased array
      ultrasound transducers for hyperthermia. However, measurements on physical
      transducers reveal differences from the idealized field profiles predicted by
      simulation. In this paper we report a method of analyzing the origins of these
      differences. The measured performance of a 15-element sparse phased array is
      described and compared with simulated fields calculated using the point source
      method. It highlighted two notable differences: First, that the focal region was
      located closer to the surface of the physical transducer than in the simulated
      fields; and second, that numerous intensity maxima were present between the
      surface of the transducer and the focal zone in the experimental data, but not in
      the simulated fields. We identified six factors that could potentially affect the
      field but were not taken into account by the default simulations, and we
      performed a sensitivity analysis on these: (i) Variation in the amplitude of the
      output from each element, (ii) the presence of square-wave harmonics in the drive
      signals, (iii) nonpistonlike vibration of elements, (iv) quantization of the
      applied phases, (v) errors in the spatial positioning of each element; and (vi)
      interelement cross-coupling. Both the independent impact of each factor and the
      interactions between multiple factors were analyzed by using a full-factorial
      experimental design composed of 64 (2(6)) simulations. The results indicated that
      nonpistonlike motion of elements is likely to be the primary cause of differences
      between the measured and modelled fields. Determination of the precise
      vibrational modes of elements in an array is complex and would require full
      finite element analysis. However, the simple vibrational mode considered within
      the present work, corresponding to the addition of a surface Rayleigh wave
      originating at the element center and propagating radially, produced simulation
      results that were in good agreement with the measured data.

PMID- 20133042
TI  - The validity of ultrasonographic assessment in cubital tunnel syndrome: the value
      of a cubital-to-humeral nerve area ratio (CHR) combined with morphologic
      features.
AB  - Diagnosis of a typical idiopathic cubital tunnel syndrome (CuTS) is straight
      forward but the work-up of mild forms is clinically challenging. The diagnostic
      value of high-resolution ultrasound (HRUS) relying solely on nerve measurements
      is doubtful. Additional textural analysis of the nerve may possibly overcome this
      drawback. Thirty-eight prospectively enrolled patients with idiopathic CuTS and
      23 healthy volunteers underwent standardized HRUS. A cubital-to-humeral nerve
      area ratio (CHR) was calculated and the texture of the most swollen nerve segment
      assessed. CHR was significantly different among patients and volunteers (p<0.001)
      but with a marked overlap. Combination of at least partial inner fascicular
      masking plus a CHR>1.4 showed a positive linear coherence with idiopathic CuTS at
      a specificity>95% and a PPV>90%. Thus, the combined textural analysis and CHR
      calculation seems a powerful tool for the sonographic diagnosis of idiopathic
      CuTS.

PMID- 20133043
TI  - Shock waves in the treatment of post-traumatic myositis ossificans.
AB  - Myositis ossificans (MO) is a fairly common evolution in sports activity and can
      be due to direct trauma or to repeated micro-injuries. The traditional
      therapeutic approach relies on a variety of treatments, such as physical therapy
      but evidence of their proven clinical efficacy is lacking. The latest therapeutic
      option is surgical removal but this is a demolitive procedure and is frequently
      associated with a significant loss of functional integrity. There are few
      articles in literature about the treatment of post-traumatic MO, and none on
      extracorporeal shock wave therapy (ESWT). We illustrate a case series of 24
      sportsmen treated with three sessions of electro-hydraulic shockwave therapy and
      an associated rehabilitation program. Only a partial reduction of the
      ossification was observed in the X-ray images but all the patients showed signs
      of functional improvement immediately after therapy. Two months after the
      therapy, a normal range of motion and no signs of weakness were observed. Three
      months after treatment, 87.5% of patients resumed regular sports activities.

PMID- 20133044
TI  - Longitudinal reference values for ductus venosus Doppler in low-risk pregnancies.
AB  - The aim of this study was to establish normal ranges of blood flow velocities and
      indices in the fetal ductus venosus (DV) during the second half of normal
      pregnancy. A Doppler study of 60 healthy pregnant women without fetal pathologies
      was performed during the second half of pregnancy. The peak systolic velocity
      (PSV), peak diastolic velocity (PDV), maximum velocity during atrial contraction
      (VAC), peak systolic velocity/maximum velocity during atrial contraction (S/A
      ratio), pulsatility index for the vein (PIV), preload index (PLI) and velocity
      index for the vein (VIV) were calculated from the DV at 4-week intervals. A
      significant increase in PSV, PDV and VAC was observed from the 20-23(6/7) to the
      28-31(6/7) weeks, with stabilization of values until the end of the pregnancy. On
      the other hand, the study showed a significant decrease for the S/A ratio, PIV,
      PLI and VIV from the 20-23(6/7) to the 28-31(6/7) weeks and remaining stable from
      then until term.

PMID- 20133045
TI  - New adaptive clutter rejection for ultrasound color Doppler imaging: in vivo
      study.
AB  - Clutter rejection is essential for accurate flow estimation in ultrasound color
      Doppler imaging. In this article, we present a new adaptive clutter rejection
      (ACR) technique where an optimum filter is dynamically selected depending upon
      the underlying clutter characteristics (e.g., tissue acceleration and power). We
      compared the performance of the ACR method with other adaptive methods, i.e.,
      down-mixing (DM) and adaptive clutter filtering (ACF), using in vivo data
      acquired from the kidney, liver and common carotid artery. With the kidney data,
      the ACR method provided an average improvement of 3.05 dB and 1.7 dB in flow
      signal-to-clutter ratio (SCR) compared with DM and ACF, respectively. With the
      liver data, SCR was improved by 2.75 dB and 1.8 dB over DM and ACF while no
      significant improvement with ACR was found in the common carotid artery data.
      Thus, the proposed adaptive method could provide more accurate flow estimation by
      improving clutter rejection in abdominal ultrasound color Doppler imaging pending
      validation.

PMID- 20133046
TI  - Three-dimensional high-frequency characterization of cancerous lymph nodes.
AB  - High-frequency ultrasound (HFU) offers a means of investigating biologic tissue
      at the microscopic level. High-frequency, three-dimensional (3-D) quantitative
      ultrasound (QUS) methods were developed to characterize freshly-dissected lymph
      nodes of cancer patients. Three-dimensional ultrasound data were acquired from
      lymph nodes using a 25.6-MHz center-frequency transducer. Each node was inked
      prior to tissue fixation to recover orientation after sectioning for 3-D
      histologic evaluation. Backscattered echo signals were processed using 3-D
      cylindrical regions-of-interest to yield four QUS estimates associated with
      tissue microstructure (i.e., effective scatterer size, acoustic concentration,
      intercept and slope). QUS estimates were computed following established methods
      using two scattering models. In this study, 46 lymph nodes acquired from 27
      patients diagnosed with colon cancer were processed. Results revealed that fully
      metastatic nodes could be perfectly differentiated from cancer-free nodes using
      slope or scatterer-size estimates. Specifically, results indicated that
      metastatic nodes had an average effective scatterer size (i.e., 37.1 +/- 1.7
      microm) significantly larger (p < 0.05) than that in cancer-free nodes (i.e., 26
      +/- 3.3 microm). Therefore, the 3-D QUS methods could provide a useful means of
      identifying small metastatic foci in dissected lymph nodes that might not be
      detectable using current standard pathology procedures.

PMID- 20133047
TI  - Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle: Case report
      and review of literature.
AB  - Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle has been
      identified as a novel and distinctive type of primary central nervous system
      neoplasm. In this report, we present a case with RGNT arising from the right
      cerebellar hemisphere. A 30-year-old female patient complained of headache for a
      five-year duration. Preoperative MRI revealed a well-circumscribed, cystic-solid
      lesion with hypo-intensity on T1-weighted image, hyper-intensity on T2-weighted
      image, and significant dot-like enhancement after IV contrast. Gross total
      resection was achieved in this case via suboccipital retro-sigmoidal approach,
      and RGNT was confirmed in the final histopathological diagnosis. RGNT of the
      fourth ventricle is a rare, benign tumor with an excellent prognosis. Operation
      is recommended as the prior protocol of treatment, and the follow-up MRI is
      necessary to evaluate the long-term prognostic effects. Currently, only one case
      of progression or recurrence has been reported in the postoperative course.

PMID- 20133048
TI  - Acute ischemic stroke treatment and the occurrence of seizures.
AB  - BACKGROUND AND OBJECTIVES: Early intravenous treatment with recombinant tissue
      plasminogen activator (rt-PA) improves the outcome of patients with an acute
      ischemic stroke. This retrospective observational study analyses whether rt-PA
      treatment also prevents the occurrence of early- and late-onset seizures.
      PATIENTS AND METHODS: Thirty-eight patients treated with rt-PA were compared to
      269 receiving anticoagulants (ACs) and 769 on antithrombotics (ATs) for an acute
      cardiac- or thrombo-embolic stroke. The epidemiological and clinical data, and
      the vascular risk factors were determined in the three groups. The incidence,
      onset and types of seizures were compared. RESULTS: The patients treated with rt
      PA had more severe stroke signs on admission and remained more dependent than
      those treated with ACs and ATs. The appearance of early-onset seizures was
      related to the severity of the stroke. The incidence of the late-onset ones
      tended to be low in the rt-PA group. None of the patients developed status
      epilepticus or epilepsy. CONCLUSION: The occurrence of early-onset seizures in
      the rt-PA treated group is related to the severity of the stroke and not to the
      treatment modality. Thrombolysis prevents partly the occurrence of late-onset
      seizures, probably, by a better reperfusion of the ischemic brain regions.

PMID- 20133049
TI  - Proteasome inhibition: a new therapeutic strategy to cancer treatment.
AB  - The ubiquitin-proteasome system is a major pathway for protein degradation.
      Targeting this pathway using proteasome inhibitors represents a novel approach
      for the treatment of cancer. Proteasome inhibitors lower cell proliferation and
      induce apoptosis in solid and hematologic malignancies through multiple
      mechanisms, including stabilization of cell cycle regulators and pro-apoptotic
      factors, stimulation of bone morphogenetic protein signaling, inhibition of
      protein translation, and sensitization to ligand-induced apoptosis. In this
      connection, proteasome inhibition activates macroautophagy, a compensatory
      protein degradation system, as well as other pro-survival signaling pathways.
      Inhibition of these auto-protective responses sensitizes cancer cells to the anti
      proliferative effects of proteasome inhibitors.

PMID- 20133050
TI  - Expression profiling identifies epoxy anthraquinone derivative as a DNA
      topoisomerase inhibitor.
AB  - To discover novel drugs for neuroblastoma treatment, we have previously screened
      a panel of drugs and identified 30 active agents against neuroblastoma cells.
      Here we performed microarray gene expression analysis to monitor the impact of
      these agents on a neuroblastoma cell line and used the connectivity map (cMAP) to
      explore putative mechanism of action of unknown drugs. We first compared the
      expression profiles of 10 compounds shared in both our dataset and cMAP database
      and observed the high connectivity scores for 7 of 10 matched drugs regardless of
      the differences of cell lines utilized. The screen of cMAP for uncharacterized
      drugs indicated the signature of Epoxy anthraquinone derivative (EAD) matched the
      profiles of multiple known DNA targeted agents (topoisomerase I/II inhibitors,
      DNA intercalators, and DNA alkylation agents) as predicted by its structure.
      Similar result was obtained by querying against our internal NB-cMAP
      (http://pob.abcc.ncifcrf.gov/cgi-bin/cMAP), a database containing the profiles of
      30 active drugs. These results suggest that Epoxy anthraquinone derivative may
      inhibit neuroblastoma cells by targeting DNA replication inhibition. Experimental
      data also demonstrate that Epoxy anthraquinone derivative indeed induces DNA
      double-strand breaks through DNA alkylation and inhibition of topoisomerase
      activity. Our study indicates that Epoxy anthraquinone derivative may be a novel
      DNA topoisomerase inhibitor that can be potentially used for treatment of
      neuroblastoma or other cancer patients.

PMID- 20133051
TI  - Chrysin sensitizes tumor necrosis factor-alpha-induced apoptosis in human tumor
      cells via suppression of nuclear factor-kappaB.
AB  - Chrysin (5,7-dihydroxyflavone) is a natural flavonoid commonly found in many
      plants. The anti-cancer property of chrysin has been demonstrated although the
      molecular mechanisms remain to be further elucidated. In the present study, we
      found that, pretreatment with chrysin greatly sensitized various human cancer
      cells to tumor necrosis factor-alpha (TNFalpha)-induced apoptosis. In the search
      of the molecular mechanisms responsible for the sensitization effect of chrysin,
      we discovered that such sensitization is closely associated with the inhibitory
      effect of chrysin on TNFalpha-mediated nuclear transcription factor-kappaB (NF
      kappaB) activation. Pretreatment with chrysin inhibited TNFalpha-induced
      degradation of Inhibitor of kappaB (IkappaB) protein and subsequent nuclear
      translocation of p65. As a result, chrysin suppressed the expression of NF-kappaB
      targeted anti-apoptotic gene, c-FLIP-L. The role of c-FLIP-L was further
      confirmed by its ectopic expression, which significantly protected cell death
      induced by combined treatment with chrysin and TNFalpha. Data from this study
      thus reveal a novel function of chrysin and enhance the value of chrysin as an
      anti-cancer agent.

PMID- 20133052
TI  - Apoptosis and lysosome membrane permeabilization induction on breast cancer cells
      by an anticarcinogenic Bowman-Birk protease inhibitor from Vigna unguiculata
      seeds.
AB  - In this work, we report the effects of a Bowman-Birk protease inhibitor, the
      Black-Eyed Pea Trypsin/Chymotrypsin Inhibitor - BTCI, purified from Vigna
      unguiculata seeds, on the MCF-7 breast cancer cells. The treatment of MCF-7 with
      200microM BTCI for 72h induced significant reduction of the cell viability and
      proliferation (arrest in S and G2/M phase). These cytostatic effects were
      accompanied by acute morphological modifications including the alteration of the
      nuclear morphology, plasma membrane fragmentation, cytoplasm disorganization,
      presence of double-membrane vesicles, mitochondrial swelling, and an increase in
      the size of lysosomes. Significative DNA fragmentation, annexin-V(+) cell number
      increase, mitochondrial membrane potential reduction, and cytoplasm acidification
      were also detected. All together, these cytostatic and cytotoxic results point
      out to BTCI-induced apoptosis cell death associated with severe cell
      morphological alterations and lysosome membrane permeabilization. Our study
      confirms the anticarcinogenic potential of Bowman-Birk protease inhibitors and
      identifies BTCI as a promising tool for drug developments aimed at the treatment
      of breast cancer.

PMID- 20133053
TI  - Combined treatment of domestic wastewater with landfill leachate by using A2/O
      process.
AB  - A set of anaerobic-anoxic-aerobic (A(2)/O) bioreactor system was designed and
      used to treat domestic wastewater mixed with landfill leachate in Datansha Sewage
      Treatment Plant in Guangzhou, south China. The optimal mixing proportion of
      combined treatment of domestic wastewater with landfill leachate and the optimal
      operating conditions for the removal efficiencies of nitrogen by using Taguchi
      orthogonal array test was conducted to evaluate the influence of parameters. The
      results showed that: the optimal volume ratio of landfill leachate and domestic
      wastewater in the A(2)/O process was 1:500. The average removal efficiencies of
      NH(4)(+)-N, TN and COD was achieved to be 96.5%, 61.0% and 81.7%, respectively in
      the case of the hydraulic retention time (HRT) of 11h, dissolved oxygen (DO) of 3
      mg L(-1), the mixed-liquid return ratio (r) of 200% and sludge return ratio (R)
      of 80% in the case of the confirmatory experiment. The pilot scale (3.8m(3))
      investigation results were applied in the large-scale (220,000 m(3)/d) combined
      treatment of sewage wastewater with landfill leachate in Guangzhou Datansha
      Domestic Sewage Wastewater Treatment Plant. The removal efficiencies of COD,
      NH(4)(+)-N, T-N and T-P were 82.65%, 92.69%, 57.10% and 76.55%, respectively.

PMID- 20133054
TI  - Determination of fast ozone oxidation rate for textile dyes by using a continuous
      quench-flow system.
AB  - To study the fast kinetic decolourisation of textile dyes by ozone a continuous
      quench-flow system was used. This system has not been used before for these
      purposes. Reaction times in the range of 7-3000 ms were explored. The reaction
      was quenched with potassium iodide, which proved to be very effective, and the
      indigo method was used to follow the ozone concentration. Dyes from the most
      representative chemical classes currently used in the textile industry, i.e. azo
      and anthraquinone, were selected. Using the initial slope method, the effect of
      dye and ozone concentrations was researched and the kinetic equations thus
      established. Using tert-butyl alcohol, as radical scavenger, and pH close to 2.5,
      the second-order rate constant of the reactant dyes at 280 K varies in the range
      of 1.20x10(4)-7.09x10(5)M(-1)s(-1); the Acid Orange 7 exhibiting thus its lowest
      value, the Acid Blue 45 its highest value and the Acid Green 25 and 27 and Direct
      Yellow 4 intermediate values (approximately 1.6x10(5)M(-1)s(-1)). Without radical
      scavenger and the pH close to 4, the reaction rate increases one order of
      magnitude, but, on the reverse, the efficiency of ozone to decolourisation
      decreases.

PMID- 20133055
TI  - On the use of carbon blacks as potential low-cost adsorbents for the removal of
      non-steroidal anti-inflammatory drugs from river water.
AB  - The adsorption of two non-steroidal anti-inflammatory drugs (NSAIDs), namely
      naproxen and ketoprofen, has been studied. Low-cost carbonaceous materials such
      as carbon blacks have been used as the adsorbents. The influence of temperature
      (20-60 degrees C), pH (3-11), ionic strength (0.01-0.1M), textural properties of
      the adsorbents (S(BET) and pore volumes) and aqueous matrix on the adsorption
      process has been analyzed. The adsorption isotherms have been determined both in
      milli-Q aqueous solution and water from the Guadiana river. Ionic strength and pH
      exert a noticeable influence on the process. In general, the removal is favored
      at low values of temperature and pH. On the contrary, an increase of the ionic
      strength seems to favor the adsorption process. The use of more porous adsorbents
      results in a more effective removal of the pollutants. Finally, the use of
      natural river water results in a noticeable increase of the removal capacity of
      naproxen and, particularly, ketoprofen. The experimental results proved that,
      under the optimal operation conditions, up to 517mg/g of naproxen and 400mg/g of
      ketoprofen may be adsorbed, which demonstrates the promising potential of these
      adsorbents for the removal of the pharmaceuticals under study.

PMID- 20133056
TI  - Synthesis and evaluation of chromate and arsenate anions extraction ability of a
      N-methylglucamine derivative of calix[4]arene immobilized onto magnetic
      nanoparticles.
AB  - In this study, 5,17-bis-[(N-methylglucamine)methyl]-25,26,27,28-tetrahydroxy
      calix[4]arene (3) was synthesized by the treatment of calix[4]arene with a
      secondary amine N-methylglucamine and formaldehyde. The calixarene derivative (3)
      was characterized by a combination of FTIR, (1)H NMR and elemental analyses.
      Followingly, using the macrocyclic building block, the compound 3 was immobilized
      by [3-(2,3-epoxypropoxy)propyl]trimethoxysilane-modified Fe(3)O(4) magnetite
      nanoparticles (EPPTMS-MN). The prepared calix[4]arene immobilized material was
      characterized by a combination of Fourier transform infrared spectroscopy (FTIR),
      transmission electron microscopy (TEM) and thermogravimetric analyses (TGA).
      Moreover, the studies regarding the removal of arsenate and dichromate ions from
      the aqueous solutions were also carried out by using the compound in solid-liquid
      extraction experiments. It was found that the calix[4]arene-based magnetic
      material has high extraction ability towards dichromate and arsenate anions in
      66% (at pH 1.5) and in 86% (at pH 3.5), respectively.

PMID- 20133057
TI  - BTEX and MTBE adsorption onto raw and thermally modified diatomite.
AB  - The removal of BTEX (benzene, toluene, ethyl-benzene and xylenes) and MTBE
      (methyl tertiary butyl ether) from aqueous solution by raw (D(R)) and thermally
      modified diatomite at 550, 750 and 950 degrees C (D(550), D(750) and D(950)
      respectively) was studied. Physical characteristics of both raw and modified
      diatomite such as specific surface, pore volume distribution, porosity and
      pH(solution) were determined, indicating important structural changes in the
      modified diatomite, due to exposure to high temperatures. Both adsorption kinetic
      and isotherm experiments were carried out. The kinetics data proved a closer fit
      to the pseudo-second order model. Maximum values for the rate constant, k(2),
      were obtained for MTBE and benzene (48.9326 and 18.0996 g mg(-1)h(-1),
      respectively) in sample D(550). The isotherm data proved to fit the Freundlich
      model more closely, which produced values of the isotherm constant 1/n higher
      than one, indicating unfavorable adsorption. The highest adsorption capacity,
      calculated through the values of the isotherm constant k(F), was obtained for
      MTBE (48.42 mg kg(-1) (mg/L)(n)) in sample D(950).

PMID- 20133058
TI  - The toxicity of naphthalene to marine Chlorella vulgaris under different nutrient
      conditions.
AB  - The toxicity of naphthalene to Chlorella vulgaris was studied under nitrogen (N)
      , phosphorus (P)-enriched and N,P-starved condition. Results showed that
      naphthalene was less toxic under N,P-starved condition. The inhibitory rates were
      less than 15.3% to C. vulgaris during 7 days exposure with the initial
      concentrations of naphthalene at 5, 10, 50, 100mg/L, respectively under N,P
      starved condition, while they were 7.5-72.3% under N,P-enriched condition. The
      malondialdehyde (MDA) content indicated that there was no oxidative damage to
      algae when the initial concentration of naphthalene was less than 10mg/L, and
      oxidative damage exhibited to algae at 50-100mg/L of naphthalene under N,P
      starved condition. Naphthalene induced oxidative damage to the algae at all
      tested concentrations (5-100mg/L) under N,P-enriched condition. The results
      indicated that there was a negative relationship between the special growth rate
      (SGR) and naphthalene concentration in the medium. Under N,P-enriched condition
      SGR of the control decreased slowly from 0.669 to 0.186. However, SGR of the
      naphthalene treated group decreased sharply during the first 2-3 days when the
      dissolved concentration of naphthalene was above 0.1mg/L, and then increased
      gradually with the evaporation of naphthalene.

PMID- 20133059
TI  - Comparison of different physico-chemical methods for the removal of toxicants
      from landfill leachate.
AB  - Our work was focused on investigation of different treatment procedures for the
      removal of toxic fractions from a landfill leachate, because sometimes the
      existing treatment in biological sequencing batch reactor (SBR) is not efficient
      enough, leading to a hazardous environmental impact of the present persistent and
      toxic compounds. The efficiency of the procedures used was monitored by chemical
      analyses and two toxicity tests (activated sludge and Vibrio fischeri). The
      existing SBR (HRT=1.9 days) removed 46-78% of COD and 96-73% of NH(4)(+)-N.
      Experiments were conducted with three landfill leachate samples expressing
      significant difference in concentrations of pollutants and with low BOD(5)/COD
      ratio (0.06/0.01/0.03). The applied methods were air stripping, adsorption to
      activated carbon and zeolite clinoptilolite and Fenton oxidation. Air stripping
      at pH 11 was a viable treatment option for the removal of ammonia nitrogen (up to
      94%) and reduction of toxicity to microorganisms. In the adsorption experiments
      in batch system with different concentration of PAC the most effective was the
      highest addition (50.0gL(-1)) where 63-92% of COD was removed followed by
      significant reduction in toxicity to V. fischeri. In the column experiments with
      clinoptilolite 45/93/100% of NH(4)(+)-N as well as 25/32/39% of COD removal was
      attained. The removal efficiency for metals followed the sequence Cr>Zn>Cd>Ni.
      The procedure with zeolite was the second most efficient one regarding reduction
      of toxicity to both organisms. Fenton oxidation at molar ratio
      Fe(2+):H(2)O(2)=1.0:10.0 assured 70-85% removal of COD but it only slightly
      reduced the toxicity.

PMID- 20133060
TI  - Immobilization of methylene blue onto bentonite and its application in the
      extraction of mercury (II).
AB  - Methylene blue was immobilized onto bentonite (BNT). The modified clay (MB-BNT)
      was used to extract Hg(2+) at pH 6.0 yielding Hg-MB-BNT. BNT, MB-BNT and Hg-MB
      BNT were characterized by X-ray diffractometry, infrared spectra, and elemental
      and thermogravimetric analyses. MB is suggested to be intercalated into the major
      phase of BNT; montmorillonite mineral (MMT), lying parallel to the
      aluminosilicate layers, with a capacity of 36 mequiv./100g. MB-BNT shows good
      stability in 0.1-1M hydrochloric or nitric acids, ammonium hydroxide, and
      concentrated Na(+), K(+) or NH(4)(+) chlorides or iodides. It shows good
      selectivity towards Hg(2+) with an extraction capacity of 37 mequiv./100g in the
      presence of I(-) giving rise to a ratio of MB/Hg(2+)/I(-) 1:1:3 in the clay
      phase. Extracted Hg(2+) could be quantitatively recovered by ammonia buffer at pH
      8.5. MB-BNT was successfully applied to recover Hg(2+) from spiked natural water
      and cinnabar mineral samples using the optimum conditions; pH 6.0, time of
      stirring 10 min and 10 mL of 0.05 M NH(4)Cl/NH(4)OH at pH 8.5 as eluent.

PMID- 20133061
TI  - Removal of sulfonamide antibiotics from water: Evidence of adsorption into an
      organophilic zeolite Y by its structural modifications.
AB  - Sulfonamide antibiotics are persistent pollutants of aquatic bodies, known to
      induce high levels of bacterial resistance. We investigated the adsorption of
      sulfadiazine, sulfamethazine, and sulfachloropyridazine sulfonamides into a
      highly dealuminated faujasite zeolite (Y) with cage window sizes comparable to
      sulfonamide dimensions. At maximal solubility the antibiotics were almost
      completely (>90%) and quickly (t<1min) removed from the water by zeolite. The
      maximal amount of sulfonamides adsorbed was 18-26% DW of dry zeolite weight, as
      evidenced by thermogravimetric analyses and accounted for about one antibiotic
      molecule per zeolitic cage. The presence of this organic inside the cage was
      revealed by unit cell parameter variations and structural deformations obtained
      by X-ray structure analyses carried out using the Rietveld method on exhausted
      zeolite. The most evident deformation effects were the lowering of the Fd-3m real
      symmetry in the parent zeolite to Fd-3 and the remarkable deformations which
      occurred in the 12-membered ring cage window after sulfadiazine or
      sulfachloropyridazine adsorption. After sulfamethazine adsorption, zeolite
      deformation caused a lowering in symmetry up to the monoclinic P2/m space group.
      The effective and irreversible adsorption of sulfonamides into organophylic Y
      zeolite makes this cheap and environmentally friendly material a suitable
      candidate for removing sulfonamides from water.

PMID- 20133062
TI  - Competitive and non-competitive adsorption/desorption of paraquat, diquat and
      difenzoquat in vineyard-devoted soils.
AB  - Mobility of agrochemicals in soils plays an important role in the fate and
      transport of contaminants in the environment. Competitive and non-competitive
      sorption experiments of three ammonium quaternary herbicides (paraquat, diquat
      and difenzoquat) onto eight vineyard soils was measured in batch experiments. Non
      competitive experiments show that paraquat (PQ) is the most strongly adsorbed (70
      97% of added PQ) followed by diquat (DQ) and difenzoquat (DFQ). The best fits
      were obtained with the Freundlich equation. In competitive experiments with
      variable mole ratios, it was found a large influence between the divalent
      cationic herbicides PQ and DQ, and between them and the monovalent herbicide DFQ,
      but DFQ did only show a scarce influence on PQ and DQ sorption. Desorption of
      herbicides into CaCl(2) showed very low values: around 11, 19 and 31% for,
      respectively, PQ, DQ and DFQ. In order to assess the ability of herbicides to
      displace others, desorption experiments were carried out by replacing Cl(2)Ca by
      any of the other two herbicides. In this case, the highest percentage of
      desorption was obtained when DFQ was desorbed with PQ (>72%) and DQ (>73%), but
      also when PQ was used to desorb DQ (100%) and vice versa (100%).

PMID- 20133063
TI  - On-line separation/preconcentration of V(IV)/V(V) in environmental water samples
      with CTAB-modified alkyl silica microcolumn and their determination by
      inductively coupled plasma-optical emission spectrometry.
AB  - A simple and selective method of flow injection microcolumn
      separation/preconcentration on-line coupled with inductively coupled plasma
      optical emission spectrometry (ICP-OES) was developed for the speciation of
      V(V)/(IV). Various factors affecting the separation/preconcentration of V(IV) and
      V(V) by conical microcolumn packed with cetyltrimethylammonium bromide (CTAB)
      modified alkyl silica have been systematically investigated. It is found that
      V(V) was quantitatively retained by the microcolumn at pH 2.0-7.0, while V(IV)
      was not retained by the microcolumn at pH 2.0-3.5 but quantitatively retained at
      pH 5.0-7.0. The two vanadium species adsorbed by the modified adsorbent were
      quantitatively desorbed by 0.10 mL of 1.0 mol L(-1) HNO(3). Therefore, V(V) and
      total vanadium could be determined by CTAB-modified alkyl silica packed
      microcolumn separation/preconcentration and on-line ICP-OES detection after
      adjusting sample solution to pH 2.5 and 6.0, respectively, and the assay of V(IV)
      was realized by subtracting V(V) from total V. The detection of limit (LOD) for
      V(V) was 0.03 microg L(-1) with an enrichment factor of 27.9 for a 3.0 mL sample
      consumption. The relative standard deviations (RSDs) (C(V(V))=C(V(IV))=5.0 microg
      L(-1), n=9) were 4.3% and 4.0% for V(V) and total V, respectively. The developed
      method was validated by the determination of V(IV) and V(V) in environmental
      water samples.

PMID- 20133064
TI  - Probing material properties of polymeric surface layers with tapping mode AFM:
      which cantilever spring constant, tapping amplitude and amplitude set point gives
      good image contrast and minimal surface damage?
AB  - A phase shift between the oscillatory motion and drive motion of an AFM
      cantilever used for tapping mode AFM imaging can be related to adhesive and
      elastic properties of surface layers. In this study it was studied how optimal
      contrast between hard and soft surface layers can be achieved while minimizing
      the surface damage. This was investigated by performing classical force-distance
      measurements while driving the cantilever as in tapping mode imaging. The
      amplitude and phase response as a function of the average tip-surface separation
      was recorded. Five different cantilevers with a wide range of spring constants
      and four different tapping amplitudes were investigated and compared. Based on
      these experiments it is concluded that too stiff cantilever, high free tapping
      amplitude and low amplitude set point value often lead to surface damage, while
      too low spring constant and low free tapping amplitude result in poor phase image
      contrast. Intermediate values where little surface damage and significant image
      contrast are obtained were identified. In all cases it was observed that the best
      image contrast was obtained when the amplitude set point was chosen such that the
      amplitude during imaging was reduced to approximately 50% of the free amplitude.

PMID- 20133065
TI  - Adjuvant aromatase inhibitor therapy: outcomes and safety.
AB  - Adjuvant therapy with the third-generation aromatase inhibitors (AIs)
      anastrozole, letrozole, and exemestane has largely replaced the use of tamoxifen
      (TAM) as standard adjuvant endocrine treatment for postmenopausal women with
      hormone-sensitive early breast cancer. Treatment strategies investigated in
      large, randomized, well-controlled clinical studies include the use of an AI as
      an upfront replacement for TAM, as an alternative to continued treatment with
      TAM, and in the extended adjuvant setting after at least 5 years of TAM. The
      efficacy of AIs over TAM has been demonstrated, particularly in terms of
      improving disease-free survival (DFS), and reductions in early distant metastasis
      with AIs may ultimately translate into improved overall survival. As AI therapy
      offers prolonged DFS, safety is an important concern over the long term. The AIs
      are better tolerated than TAM in terms of troublesome gynecologic adverse events
      such as vaginal bleeding and discharge, as well as life-threatening complications
      such as venous thromboembolic events and endometrial cancer. On the other hand,
      AI therapy has been associated with losses in bone density and a potential effect
      on lipids and cardiovascular risk. In trials comparing AIs with TAM, only limited
      conclusions can be made because of the putative cardioprotective, lipid-lowering,
      and bone-sparing effects of TAM. Studies comparing AIs with placebo, and/or in
      healthy women, may be more useful in understanding the long-term safety of
      adjuvant AI therapy. Results of ongoing safety analyses within some of the large
      AI trials should provide further insight into the long-term tolerability of AI
      therapy in the adjuvant setting.

PMID- 20133066
TI  - Dynamic multileaf collimator tracking of respiratory target motion based on a
      single kilovoltage imager during arc radiotherapy.
AB  - PURPOSE: To demonstrate and characterize dynamic multileaf collimator (DMLC)
      tracking of respiratory moving targets that are spatially localized with a single
      kV X-ray imager during arc radiotherapy. METHODS AND MATERIALS: During delivery
      of an arc field (358 degrees gantry rotation, 72-sec duration, circular field
      shape), the three-dimensional (3D) position of a fiducial marker in a phantom was
      estimated in real time from fluoroscopic kV X-ray images acquired orthogonally to
      the treatment beam axis. A prediction algorithm was applied to account for system
      latency (570 ms) before the estimated marker position was used for DMLC aperture
      adaptation. Experiments were performed with 12 patient-measured tumor
      trajectories that were selected from 160 trajectories (46 patients) and
      reproduced by a programmable phantom. Offline, the 3D deviation of the estimated
      phantom position from the actual position was quantified. The two-dimensional
      (2D) beam-target deviation was quantified as the positional difference between
      the MLC aperture center and the marker in portal images acquired continuously
      during experiments. Simulations of imaging and treatment delivery extended the
      study to all 160 tumor trajectories and to arc treatments of 3-min and 5-min
      duration. RESULTS: In the experiments, the mean root-mean-square deviation was
      1.8 mm for the 3D target position and 1.5 mm for the 2D aperture position.
      Simulations agreed with this to within 0.1 mm and resulted in mean 2D root-mean
      square beam-target deviations of 1.1 mm for all 160 trajectories for all
      treatment durations. The deviations were mainly caused by system latency (570
      ms). CONCLUSIONS: Single-imager DMLC tracking of respiratory target motion during
      arc radiotherapy was implemented, providing less than 2-mm geometric uncertainty
      for most trajectories.

PMID- 20133067
TI  - Predicting post-external beam radiation therapy PSA relapse of prostate cancer
      using pretreatment MRI.
AB  - PURPOSE: To investigate whether pretreatment endorectal magnetic resonance
      imaging (MRI) findings can predict biochemical relapse in patients with
      clinically localized prostate cancer treated with external beam radiation therapy
      (EBRT). METHODS AND MATERIALS: Between January 2000 and January 2002, 224
      patients (median age, 69 years; age range, 45-82 years) with biopsy-proven
      prostate cancer underwent endorectal MRI before high-dose (>=81Gy) EBRT. The
      value of multiple clinical and MRI variables in predicting prostate-specific
      antigen (PSA) relapse at 5 years was determined by use of univariate and
      multivariate stepwise Cox regression. Clinical variables included pretreatment
      PSA, clinical T stage, Gleason score, use of neoadjuvant hormonal therapy, and
      radiation dose. Magnetic resonance imaging variables, derived from retrospective
      consensus readings by two radiologists, were used to measure intraprostatic and
      extraprostatic tumor burden. RESULTS: After a median follow-up of 67 months, PSA
      relapse developed in 37 patients (16.5%). The significant predictors of PSA
      relapse on univariate analysis were pretreatment PSA, clinical T stage, and
      multiple MRI variables, including MRI TN stage score; extracapsular extension
      (ECE) status; number of sextants involved by ECE, all lesions, or index
      (dominant) lesion; apical involvement; and diameter and volume of index lesion.
      Pretreatment PSA and ECE status were the only significant independent predictors
      on multivariate analysis (p < 0.05 for both). Extracapsular extension status was
      associated with the highest hazard ratio, 3.04; 5-year PSA relapse rates were 7%
      for no ECE, 20% for unilateral ECE, and 48% for bilateral ECE. CONCLUSIONS:
      Magnetic resonance imaging findings can be used to predict post-EBRT PSA relapse,
      with ECE status on MRI and pretreatment PSA being significant independent
      predictors of this endpoint.

PMID- 20133068
TI  - Multicenter, phase 3 trial comparing selenium supplementation with observation in
      gynecologic radiation oncology.
AB  - PURPOSE: We assessed whether adjuvant supplementation with selenium improves the
      selenium status and reduces side effects of patients treated by radiotherapy (RT)
      for cervical and uterine cancer. METHODS AND MATERIALS: Whole-blood selenium
      concentrations were measured in patients with cervical cancer (n = 11) and
      uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT,
      and 6 weeks after RT. Patients with initial selenium concentrations of less than
      84MUg/L were randomized before RT either to receive 500 MUg of selenium (in the
      form of sodium selenite [selenase, biosyn Arzneimittel GmbH, Fellbach, Germany])
      by mouth on the days of RT and 300 MUg of selenium on the days without RT or to
      receive no supplement during RT. The primary endpoint of this multicenter Phase 3
      study was to assess the efficiency of selenium supplementation during RT; the
      secondary endpoint was to decrease radiation-induced diarrhea and other RT
      dependent side effects. RESULTS: A total of 81 patients were randomized. We
      enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium
      levels did not differ between the SG and CG upon study initiation but were
      significantly higher in the SG at the end of RT. The actuarial incidence of
      diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2)
      in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood
      parameters, Eastern Cooperative Oncology Group performance status, and self
      reported quality of life were not different between the groups. CONCLUSIONS:
      Selenium supplementation during RT is effective in improving blood selenium
      status in selenium-deficient cervical and uterine cancer patients and reduces the
      number of episodes and severity of RT-induced diarrhea.

PMID- 20133069
TI  - Gated treatment delivery verification with on-line megavoltage fluoroscopy.
AB  - PURPOSE: To develop and clinically demonstrate the use of on-line real-time
      megavoltage (MV) fluoroscopy for gated treatment delivery verification. METHODS
      AND MATERIALS: Megavoltage fluoroscopy (MVF) image sequences were acquired using
      a flat panel equipped for MV cone-beam CT in synchrony with the respiratory
      signal obtained from the Anzai gating device. The MVF images can be obtained
      immediately before or during gated treatment delivery. A prototype software tool
      (named RTReg4D) was developed to register MVF images with phase-sequenced
      digitally reconstructed radiograph images generated from the treatment planning
      system based on four-dimensional CT. The image registration can be used to
      reposition the patient before or during treatment delivery. To demonstrate the
      reliability and clinical usefulness, the system was first tested using a thoracic
      phantom and then prospectively in actual patient treatments under an
      institutional review board-approved protocol. RESULTS: The quality of the MVF
      images for lung tumors is adequate for image registration with phase-sequenced
      digitally reconstructed radiographs. The MVF was found to be useful for
      monitoring inter- and intrafractional variations of tumor positions. With the
      planning target volume contour displayed on the MVF images, the system can verify
      whether the moving target stays within the planning target volume margin during
      gated delivery. CONCLUSIONS: The use of MVF images was found to be clinically
      effective in detecting discrepancies in tumor location before and during
      respiration-gated treatment delivery. The tools and process developed can be
      useful for gated treatment delivery verification.

PMID- 20133070
TI  - Predictive and prognostic significance of glutathione levels and DNA damage in
      cervix cancer patients undergoing radiotherapy.
AB  - PURPOSE: To assess the predictive significance of serum glutathione (GSH) and
      tumor tissue DNA damage in the treatment of cervical cancer patients undergoing
      chemoradiotherapy. METHODS AND MATERIALS: This study included subjects undergoing
      hysterectomy (for normal cervix tissue) and cervical cancer patients who
      underwent conventional concurrent chemoradiotherapy (cisplatin once per week for
      5 weeks with concurrent external radiotherapy of 2 Gy per fraction for 5 weeks,
      followed by two applications of intracavitary brachytherapy once per week after 2
      weeks' rest). Blood was collected after two fractions, whereas both blood and
      tissues were collected after five fractions of radiotherapy in separate groups of
      subjects. Serum for total GSH content and tissues were processed for single-cell
      gel electrophoresis (SCGE) assay for DNA damage analysis. Clinical tumor
      radioresponse was assessed 2 months after the completion of treatment as complete
      responders (CR) (100% shrinkage), partial responders (PR) (>50%), and
      nonresponders (NR) (<50%). RESULTS: Serum GSH content depleted significantly
      after a total dose of 4 Gy and 10 Gy of radiotherapy with a single dose of
      cisplatin, which was significantly lesser in NR than of CR patients. Similarly,
      Olive Tail Moment, the index of DNA damage, indicated significantly higher values
      in the fifth fraction of radiotherapy (5-RT) than in pretreatment. The DNA damage
      after 5-RT in the NR subgroup was significantly lower than that of CR.
      CONCLUSIONS: Serum GSH analysis and tumor tissue SCGE assay found to be useful
      parameters for predicting chemoradioresponse prior to and also at an early stage
      of treatment of cervical cancers.

PMID- 20133071
TI  - 18F-FDG PET definition of gross tumor volume for radiotherapy of lung cancer: is
      the tumor uptake value-based approach appropriate for lymph node delineation?
AB  - PURPOSE: Positron emission tomography (PET) with the glucose analogue [18F]
      fluoro-2-deoxy-D-glucose ((18)F-FDG-PET) has been used in radiation treatment
      planning for non-small-cell carcinoma. To date, lymph nodes have been contoured
      according to the uptake of the tumor. This prospective study was performed to
      evaluate if nodal volume delineates according to FDG uptake within the primary
      tumor (PET-GTVnt) is suitable for nodal target volume delineation or if
      individualized nodal FDG uptake measure (PET-GTVnn) is necessary to better nodal
      target definition. METHODS AND MATERIALS: Forty cases, who underwent a diagnostic
      (18)F-FDG PET/computed tomography (CT) scan, were included. Two PET-based GTVs
      for each lymph node were contoured and compared. First, we used an isocontour of
      40% of the maximum tumor uptake (PET-GTVnt). Second, an isocontour of 40% of the
      maximum uptake of each node (PET-GTVnn) was employed. To avoid interobserver
      variability, this was carried out by the same radiation oncologist. Afterwards,
      the difference between both lymph node volumes was plotted against the ratio of
      the maximum uptakes (I(n)/I(t)) in a linear regression analysis. RESULTS:
      Compared with CT-based lymph node volume (CT-GTVn), the intraclass correlation
      coefficient of PET-GTVnn was higher than the coefficient of PET-GTVnt (p <
      0.001). All cases could be divided into four groups: undetected (17.5%), detected
      but overestimated (10%), detected but underestimated (35%), and correctly
      detected (37.5%). CONCLUSIONS: If a method of automatic delineation shall be
      applied, this method must be applied to every lesion separately. However, to
      facilitate the delineation in daily practice, when I(n)/I(t) is <=25%, lymph
      nodes could be delineated in accordance with tumor uptake, keeping an absolute
      difference in radii <5 mm.

PMID- 20133072
TI  - Stereotactic radiosurgery for single brainstem metastases: the cleveland clinic
      experience.
AB  - PURPOSE: To assess the imaging and clinical outcomes of patients with single
      brainstem metastases treated with stereotactic radiosurgery (SRS). MATERIALS AND
      METHODS: We retrospectively reviewed the data from patients with single brainstem
      metastases treated with SRS. Locoregional control and survival were calculated
      using the Kaplan-Meier method. Prognostic factors were assessed using a Cox
      proportional hazards model. RESULTS: Between 1997 and 2007, 43 patients with
      single brainstem metastases were treated with SRS. The median age at treatment
      was 59 years, the median Karnofsky performance status was 80, and the median
      follow-up was 5.3 months. The median dose was 15 Gy (range, 9.6-24), and the
      median conformality and heterogeneity index was 1.7 and 1.9, respectively. The
      median survival was 5.8 months from the procedure date. Of the 33 patient with
      post-treatment imaging available, a complete radiographic response was achieved
      in 2 (4.7%), a partial response in 8 (18.6%), and stable disease in 23 (53.5%).
      The 1-year actuarial rate of local control, distant brain control, and overall
      survival was 85%, 38.3%, and 31.5%, respectively. Of the 43 patients, 8 (19%)
      died within 2 months of undergoing SRS, and 15 (36%) died within 3 months. On
      multivariate analysis, greater performance status (hazard ratio [HR], 0.95, p =
      .004), score index for radiosurgery (HR, 0.7; p = .004), graded prognostic
      assessment score (HR, 0.48; p = .003), and smaller tumor volume (HR, 1.23, p =
      .002) were associated with improved survival. No Grade 3 or 4 toxicities were
      observed. CONCLUSION: The results of our study have shown that SRS is a safe and
      effective local therapy for patients with brainstem metastases.

PMID- 20133073
TI  - Dose gradient near target-normal structure interface for nonisocentric CyberKnife
      and isocentric intensity-modulated body radiotherapy for prostate cancer.
AB  - PURPOSE: The treatment planning quality between nonisocentric CyberKnife (CK) and
      isocentric intensity modulation treatment was studied for hypofractionated
      prostate body radiotherapy. In particular, the dose gradient across the target
      and the critical structures such as the rectum and bladder was characterized.
      METHODS AND MATERIALS: In the present study, patients treated with CK underwent
      repeat planning for nine fixed-field intensity-modulated radiotherapy (IMRT)
      using identical contour sets and dose-volume constraints. To calculate the dose
      falloff, the clinical target volume contours were expanded 30 mm anteriorly and
      posteriorly and 50 mm uniformly in other directions for all patients in the CK
      and IMRT plans. RESULTS: We found that all the plans satisfied the dose-volume
      constraints, with the CK plans showing significantly better conformity than the
      IMRT plans at a relative greater dose inhomogeneity. The rectal and bladder
      volumes receiving a low dose were also lower for CK than for IMRT. The average
      conformity index, the ratio of the prescription isodose volume and clinical
      target volume, was 1.18 +/- 0.08 for the CK plans vs. 1.44 +/- 0.11 for the IMRT
      plans. The average homogeneity index, the ratio of the maximal dose and the
      prescribed dose to the clinical target volume, was 1.45 +/- 0.12 for the CK plans
      vs. 1.28 +/- 0.06 for the IMRT plans. The average percentage of dose falloff was
      2.9% +/- 0.8%/mm for CK and 3.1% +/- 1.0%/mm for IMRT in the anterior direction,
      3.8% +/- 1.6%/mm for CK and 3.2% +/- 1.9%/mm for IMRT in the posterior direction,
      and 3.6% +/- 0.4% for CK and 3.6% +/- 0.4% for IMRT in all directions.
      CONCLUSION: Nonisocentric CK was as capable of producing equivalent fast dose
      falloff as high-number fixed-field IMRT delivery.

PMID- 20133074
TI  - Lack of correlation between external fiducial positions and internal tumor
      positions during breath-hold CT.
AB  - PURPOSE: For thoracic tumors, if four-dimensional computed tomography (4DCT) is
      unavailable, the internal margin can be estimated by use of breath-hold (BH) CT
      scans acquired at end inspiration (EI) and end expiration (EE). By use of
      external surrogates for tumor position, BH accuracy is estimated by minimizing
      the difference between respiratory extrema BH and mean equivalent-phase free
      breathing (FB) positions. We tested the assumption that an external surrogate for
      BH accuracy correlates with internal tumor positional accuracy during BH CT.
      METHODS AND MATERIALS: In 16 lung cancer patients, 4DCT images, as well as BH CT
      images at EI and EE, were acquired. Absolute differences between BH and mean
      equivalent-phase (FB) positions were calculated for both external fiducials and
      gross tumor volume (GTV) centroids as metrics of external and internal BH
      accuracy, respectively, and the results were correlated. RESULTS: At EI, the
      absolute difference between mean FB and BH fiducial displacement correlated
      poorly with the absolute difference between FB and BH GTV centroid positions on
      CT images (R(2) = 0.11). Similarly, at EE, the absolute difference between mean
      FB and BH fiducial displacements correlated poorly with the absolute difference
      between FB and BH GTV centroid positions on CT images (R(2) = 0.18). CONCLUSIONS:
      External surrogates for tumor position are not an accurate metric of BH accuracy
      for lung cancer patients. This implies that care should be taken when using such
      an approach because an incorrect internal margin could be generated.

PMID- 20133075
TI  - Renal atrophy secondary to chemoradiotherapy of abdominal malignancies.
AB  - PURPOSE: To identify factors predictive of renal atrophy after chemoradiotherapy
      of gastrointestinal malignancies. METHODS AND MATERIALS: Patients who received
      chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were
      identified for this study evaluating change in kidney size and function after RT.
      Imaging and biochemical data were obtained before and after RT in 6-month
      intervals. Kidney size was defined by craniocaudal measurement on CT images. The
      primarily irradiated kidney (PK) was defined as the kidney that received the
      greater mean kidney dose. Receiver operating characteristic (ROC) curves were
      generated to predict risk for renal atrophy. RESULTS: Of 130 patients, median age
      was 64 years, and 51.5% were male. Most primary disease sites were pancreas and
      periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine
      clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after
      completion of chemoradiation. Compensatory hypertrophy of the non-PK was not
      seen. Percentage volumes of the PK receiving >=10 Gy (V(10)), 15 Gy (V(15)), and
      20 Gy (V(20)) were significantly associated with renal atrophy 1 year after RT (p
      = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for
      V(10), V(15), and V(20) to predict >5% decrease in PK size were 0.760, 0.760, and
      0.762, respectively. CONCLUSIONS: Significant detriments in PK size and renal
      function were seen after abdominal RT. The V(10), V(15), and V(20) were
      predictive of risk for PK atrophy 1 year after RT. Analyses suggest the
      association of lower-dose renal irradiation with subsequent development of renal
      atrophy.

PMID- 20133076
TI  - Fractionated conformal radiotherapy in the management of cavernous sinus
      meningiomas: long-term functional outcome and tumor control at a single
      institution.
AB  - PURPOSE: To evaluate long-term outcome of cavernous sinus meningioma (CSM)
      treated with fractionated conformal radiotherapy (FCR). PATIENTS AND METHODS:
      Fifty-three patients with CSMs (16 men [30.2%], 37 women [69.8%], aged 53 +/-
      13.0 years [mean +/- SD]) were treated by FCR. In 28 patients (52.8%) FCR was
      performed as first-line treatment and in 25 patients (47.2%) as adjuvant
      treatment. All patients received FCR with a dose of 52.9 +/- 1.8 Gy in 29.4 +/-
      1.0 fractions over 6 weeks. Dose per fraction was 1.9 +/- 0.1 Gy. Radiotherapy
      was delivered stereotactically in 47 cases (88.7%) and conformally in 6 (11.3%)
      RESULTS: The median follow-up was 6.9 years (range, 3-19 years). According to
      Sekhar's classification, 19 patients (35.8%) were Grade 1-2, 30 patients (56.6%)
      were Grade 3-4, and 4 patients (7.6%) were Grade 5. Pretreatment tumor volume was
      determined in 46 patients, and tumor volume was 12.6 +/- 8.2 cm(3). In these
      patients, the distance between tumor and optic apparatus was 1.62 +/- 1.2 mm.
      Actuarial 5- and 10-year progression-free survival rates were 98.1% and 95.8%,
      respectively. Clinical improvement was observed in 31 patients (58.5%), and 20
      patients (37.7%) remained unchanged. Radiologic response was observed in 18
      patients (30.2%), and 35 patients (66.0%) showed stable lesions. Two patients
      (3.8%) showed tumor progression during follow-up. Transient morbidity was
      observed in 3 patients (5.7%) and permanent morbidity in 1 (1.9%). CONCLUSION:
      Fractionated conformal radiotherapy affords satisfactory long-term tumor control
      and low treatment morbidity.

PMID- 20133077
TI  - Angiogenic blockade and radiotherapy in hepatocellular carcinoma.
AB  - PURPOSE: We report our preliminary experience of combining sunitinib and helical
      tomotherapy in patients with advanced HCC. METHODS AND MATERIALS: Records of
      patients with advanced hepatocellular carcinoma (HCC) treated with helical
      tomotherapy and sunitinib after radiation therapy (RT) from March 2007 to August
      2008 were retrospectively reviewed. We report acute toxicities, radiologic
      response, serial alpha-fetoprotein (AFP) kinetics, and survival. RESULTS: Of 23
      evaluable patients, 60% had >or=2 hepatic lesions, extrahepatic disease was
      present in 5 (21.7%), and all received 2 tablets (25 mg) of sunitinib at least 1
      week before, during, and 2 weeks after RT. Thirteen patients continued
      maintenance sunitinib after RT until disease progression. Hypofractionated RT
      with a median target dose of 52.5 Gy/15 fractions was delivered. An objective
      response was achieved in 74% of patients. The 1-year survival rate was 70%, with
      median survival of 16 months. Multivariate analysis showed that maintenance
      sunitinib was the most significant factor for survival. The time to progression
      was 10 months in the maintenance group compared with 4 months in the control
      group. Eighteen out of 21 patients with elevated AFP (85.7%) had >or=50% decline
      of AFP within 2 months after RT. There were three episodes of upper
      gastrointestinal bleeding and one episode of pancreatitis; 10 patients had
      >or=Grade 2 elevation of liver enzymes, and 15 had >or=Grade 2 thrombocytopenia.
      CONCLUSIONS: These preliminary results suggest that sunitinib and helical
      tomotherapy yield high Response Evaluation Criteria in Solid Tumors (RECIST) and
      AFP response rates in advanced HCC with an acceptable safety profile. Maintenance
      sunitinib after RT potentially prolongs survival. A randomized trial is
      warranted.

PMID- 20133078
TI  - Increased detection of lymphatic vessel invasion by D2-40 (podoplanin) in early
      breast cancer: possible influence on patient selection for accelerated partial
      breast irradiation.
AB  - PURPOSE: Several international trials are currently investigating accelerated
      partial breast irradiation (APBI) for patients with early-stage breast cancer.
      According to existing guidelines, patients with lymphatic vessel invasion (LVI)
      do not qualify for APBI. D2-40 (podoplanin) significantly increases the frequency
      of LVI detection compared with conventional hematoxylin and eosin (HE) staining
      in early-stage breast cancer. Our purpose was to retrospectively assess the
      hypothetical change in management from APBI to whole breast radiotherapy with the
      application of D2-40. PATIENTS AND METHODS: Immunostaining with D2-40 was
      performed on 254 invasive breast tumors of 247 patients. The following criteria
      were used to determine the eligibility for APBI: invasive ductal adenocarcinoma
      of < or =3 cm, negative axillary node status (N0), and unifocal disease. Of the
      247 patients, 74 with available information concerning LVI, as detected by D2-40
      immunostaining and routine HE staining, formed our study population. RESULTS:
      Using D2-40, our results demonstrated a significantly greater detection rate (p =
      .031) of LVI compared with routine HE staining. LVI was correctly identified by
      D2-40 (D2-40-positive LVI) in 10 (13.5%) of 74 tumors. On routine HE staining, 4
      tumors (5.4%) were classified as HE-positive LVI. Doublestaining of these
      specimens with D2-40 unmasked false-positive LVI status in 2 (50%) of the 4
      tumors. According to the current recommendations for APBI, immunostaining with D2
      40 would have changed the clinical management from APBI to whole breast
      radiotherapy in 8 (10.8%) of 74 patients and from whole breast radiotherapy to
      APBI in 2 patients (2.7%). CONCLUSION: These data support the implementation of
      D2-40 immunostaining in the routine workup to determine a patient's eligibility
      for APBI.

PMID- 20133079
TI  - Stereotactic radiosurgery for treatment of spinal metastases recurring in close
      proximity to previously irradiated spinal cord.
AB  - PURPOSE: As the spinal cord tolerance often precludes reirradiation with
      conventional techniques, local recurrence within a previously irradiated field
      presents a treatment challenge. METHODS AND MATERIALS: We retrospectively
      reviewed 51 lesions in 42 patients treated from 2002 to 2008 whose spinal
      metastases recurred in a previous radiation field (median previous spinal cord
      dose of 40 Gy) and were subsequently treated with stereotactic radiosurgery
      (SRS). RESULTS: SRS was delivered to a median marginal dose of 20 Gy (range, 10
      30 Gy) in 1-5 fractions (median, 2), targeting a median tumor volume of 10.3
      cm(3) (range, 0.2-128.6 cm(3)). Converting the SRS regimens with the linear
      quadratic model (alpha/beta = 3), the median spinal cord maximum single-session
      equivalent dose (SSED) was 12.1 Gy(3) (range, 4.7-19.3 Gy(3)). With a median
      follow-up of 7 months (range, 2-47 months), the Kaplan-Meier local control and
      overall survival rates at 6/12 months were 87%/73% and 81%/68%, respectively. A
      time to retreatment of <=12 months and the combination of time to retreatment of
      <=12 months with an SSED of <15 Gy(10) were significant predictors of local
      failure on univariate and multivariate analyses. In patients with a retreatment
      interval of <12 months, 6/12 month local control rates were 88%/58%, with a SSED
      of >15 Gy(10), compared to 45%/0% with <15 Gy(10), respectively. One patient (2%)
      experienced Grade 4 neurotoxicity. CONCLUSION: SRS is safe and effective in the
      treatment of spinal metastases recurring in previously irradiated fields. Tumor
      recurrence within 12 months may correlate with biologic aggressiveness and
      require higher SRS doses (SSED >15 Gy(10)). Further research is needed to define
      the partial volume retreatment tolerance of the spinal cord and the optimal
      target dose.

PMID- 20133080
TI  - Prognostic factors after extraneural metastasis of medulloblastoma.
AB  - PURPOSE: To review the existing literature regarding the characteristics,
      prognostic factors, treatment, and survival of patients with medulloblastoma, who
      develop extraneural metastasis (ENM). METHODS AND MATERIALS: A PubMed search of
      English language articles from 1961 to 2007 was performed, yielding 47 articles
      reporting on 119 patients. Factors analyzed included age, time interval to
      development of ENM, ENM location, central nervous system (CNS) involvement,
      treatment, and outcome. RESULTS: Sites of ENM included bone in 84% of patients,
      bone marrow in 27% of patients, lymph nodes in 15% of patients, lung in 6% of
      patients, and liver in 6% of patients. Median survival was 8 months after
      diagnosis of ENM. The 1-, 2-, and 5-year overall survival (OS) rates after
      diagnosis of ENM were 41.9%, 31.0%, and 26.0%, respectively. The 1-, 2-, and 5
      year progression-free survival (PFS) rates after diagnosis of ENM were 34.5%,
      23.2%, and 13.4%, respectively. For patients without CNS involvement at the time
      of ENM diagnosis, the 1-, 2-, and 5-year OS rates for those treated with and
      without radiotherapy (RT) were 82.4%, 64.8%, and 64.8% vs. 51.0%, 36.6%, and
      30.5%, respectively (p = 0.03, log-rank test). RT did not significantly improve
      OS or PFS rates for those with CNS involvement. Concurrent CNS involvement, ENM
      in the lung or liver, a time interval of <18 months to development of ENM, and a
      patient age of <16 years at ENM diagnosis were found to be negative prognostic
      factors for both OS and PFS. CONCLUSIONS: Several prognostic factors were
      identified for patients with ENM from medulloblastoma. Patients without
      concurrent CNS involvement, who received RT after ENM diagnosis had an OS and PFS
      benefit compared to those who did not receive RT.

PMID- 20133081
TI  - Preoperative radiotherapy of advanced rectal cancer with capecitabine and
      oxaliplatin with or without cetuximab: A pooled analysis of three prospective
      phase I-II trials.
AB  - PURPOSE: A pooled analysis of three prospective trials of preoperative
      radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine
      with or without cetuximab was performed to evaluate the impact of additional
      cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG)
      grades. METHODS AND MATERIALS: Of 202 patients, 172 patients met the inclusion
      criteria (primary tumor stage II/III, M0). All patients received concurrent RCT,
      and 46 patients received additional cetuximab therapy. A correlation of
      pretreatment clinicopathologic factors and cetuximab treatment with early pCR
      rates (TRG > 50%) was performed with univariate and multivariate analyses.
      Toxicity data were recorded for all patients. RESULTS: Of 172 patients, 24 (14%)
      patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the
      surgical specimen assessment after preoperative treatment. Age, gender, and T/N
      stages, as well as localization of the tumor, were not associated with pCR or
      good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with
      concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was
      found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was
      validated by a multivariate analysis with all available clinical factors (p =
      0.0037). Acute toxicity and surgical complications were not increased with
      additional cetuximab. CONCLUSIONS: Triple therapy with RCT and cetuximab seems to
      be feasible, with no unexpected toxicity. Early response assessment (TRG),
      however, suggests subadditive interaction. A longer follow-up (and finally
      randomized trials) is needed to draw any firm conclusions with respect to local
      and distant failure rates.

PMID- 20133082
TI  - Phase I trial of bortezomib and concurrent external beam radiation in patients
      with advanced solid malignancies.
AB  - PURPOSE: To determine the maximal tolerated dose of bortezomib with concurrent
      external beam radiation therapy in patients with incurable solid malignant tumors
      requiring palliative therapy. METHODS AND MATERIALS: An open label, dose
      escalation, phase I clinical trial evaluated the safety of three dose levels of
      bortezomib administered intravenously (1.0 mg/m(2), 1.3 mg/m(2), and 1.6 mg/m(2)/
      dose) once weekly with concurrent radiation in patients with histologically
      confirmed solid tumors and a radiographically appreciable lesion suitable for
      palliative radiation therapy. All patients received 40 Gy in 16 fractions to the
      target lesion. Dose-limiting toxicity was the primary endpoint, defined as any
      grade 4 hematologic toxicity, any grade >=3 nonhematologic toxicity, or any
      toxicity requiring treatment to be delayed for >=2 weeks. RESULTS: A total of 12
      patients were enrolled. Primary sites included prostate (3 patients), head and
      neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient),
      kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum
      tolerated dose was not realized with a maximum dose of 1.6 mg/m(2). One case of
      dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be
      unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10
      patients). Common grade 1 to 2 events included nausea (7 patients), infection
      without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5
      patients). CONCLUSIONS: The combination of palliative external beam radiation
      with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m(2) is well
      tolerated in patients with metastatic solid tumors. The maximum tolerated dose of
      once weekly bortezomib delivered concurrently with radiation therapy is greater
      than 1.6 mg/m(2).

PMID- 20133083
TI  - Evaluating the Phoenix definition of biochemical failure after (125)I prostate
      brachytherapy: Can PSA kinetics distinguish PSA failures from PSA bounces?
AB  - PURPOSE: To evaluate the prostate-specific antigen (PSA) kinetics of PSA failure
      (PSAf) and PSA bounce (PSAb) after permanent (125)I prostate brachytherapy (PB).
      METHODS AND MATERIALS: The study included 1,006 consecutive low and "low tier"
      intermediate-risk patients treated with (125)I PB, with a potential minimum
      follow-up of 4 years. Patients who met the Phoenix definition of biochemical
      failure (nadir + 2 ng/mL(-1)) were identified. If the PSA subsequently fell to
      <=0.5 ng/mL(-1)without intervention, this was considered a PSAb. All others were
      scored as true PSAf. Patient, tumor and dosimetric characteristics were compared
      between groups using the chi-square test and analysis of variance to evaluate
      factors associated with PSAf or PSAb. RESULTS: Median follow-up was 54 months. Of
      the 1,006 men, 57 patients triggered the Phoenix definition of PSA failure, 32
      (56%) were true PSAf, and 25 PSAb (44%). The median time to trigger nadir + 2 was
      20.6 months (range, 6-36) vs. 49 mo (range, 12-83) for PSAb vs. PSAf groups (p <
      0.001). The PSAb patients were significantly younger (p < 0.0001), had shorter
      time to reach the nadir (median 6 vs. 11.5 months, p = 0.001) and had a shorter
      PSA doubling time (p = 0.05). Men younger than age 70 who trigger nadir +2 PSA
      failure within 38 months of implant have an 80% likelihood of having PSAb and 20%
      chance of PSAf. CONCLUSIONS: With adequate follow-up, 44% of PSA failures by the
      Phoenix definition in our cohort were found to be benign PSA bounces. Our study
      reinforces the need for adequate follow-up when reporting PB PSA outcomes, to
      ensure accurate estimates of treatment efficacy and to avoid unnecessary
      secondary interventions.

PMID- 20133084
TI  - Effect of radiotherapy interruptions on survival in medicare enrollees with local
      and regional head-and-neck cancer.
AB  - PURPOSE: To investigate whether interruptions in radiotherapy are associated with
      decreased survival in a population-based sample of head-and-neck cancer patients.
      METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results
      Medicare linked database we identified Medicare beneficiaries aged 66 years and
      older diagnosed with local-regional head-and-neck cancer during the period 1997
      2003. We examined claims records of 3864 patients completing radiotherapy for the
      presence of one or more 5-30-day interruption(s) in therapy. We then performed
      Cox regression analyses to estimate the association between therapy interruptions
      and survival. RESULTS: Patients with laryngeal tumors who experienced an
      interruption in radiotherapy had a 68% (95% confidence interval, 41-200%)
      increased risk of death, compared with patients with no interruptions. Patients
      with nasal cavity, nasopharynx, oral, salivary gland, and sinus tumors had
      similar associations between interruptions and increased risk of death, but these
      did not reach statistical significance because of small sample sizes.
      CONCLUSIONS: Treatment interruptions seem to influence survival time among
      patients with laryngeal tumors completing a full course of radiotherapy. At all
      head-and-neck sites, the association between interruptions and survival is
      sensitive to confounding by stage and other treatments. Further research is
      needed to develop methods to identify patients most susceptible to interruption
      induced mortality.

PMID- 20133085
TI  - Correlation between acute and late toxicity in 973 prostate cancer patients
      treated with three-dimensional conformal external beam radiotherapy.
AB  - PURPOSE: To analyze the correlation between acute and late injury in 973 prostate
      cancer patients treated with radiotherapy and to evaluate the effect of patient-,
      tumor-, and treatment-related variables on toxicity. METHODS AND MATERIALS: Of
      the 973 patients, 542 and 431 received definitive or postprostatectomy
      radiotherapy, respectively. Three-dimensional conformal radiotherapy included a
      six-field technique and two-dynamic arc therapy. Toxicity was classified
      according to the Radiation Therapy Oncology Group/European Organization for
      Research and Treatment of Cancer criteria. The correlation between acute and late
      toxicity (incidence and severity) was assessed. RESULTS: Multivariate analysis
      showed that age </=65 years (p = .06) and use of the three-dimensional, six-field
      technique (p <.0001) correlated significantly with greater acute rectal toxicity.
      The three-dimensional, six-field technique (p = .0002), dose >70 Gy (p = .014),
      and radiotherapy duration (p = .05) correlated with greater acute urinary
      toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated
      with late rectal injury on multivariate analysis. Late urinary toxicity
      correlated with acute urinary events (p <.0001) and was inversely related to the
      use of salvage radiotherapy (p = .018). A highly significant correlation was
      found between the incidence of acute and late events for both rectal (p <.001)
      and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or
      greater) was predictive for the severity of late toxicity for both rectal and
      urinary events (p <.001). CONCLUSION: The results of our study have shown that
      the risk of acute reactions depends on both patient-related (age) and treatment
      related (dose, technique) factors. Acute toxicity was an independent significant
      predictor of late toxicity. These findings might help to predict and prevent late
      radiotherapy-induced complications.

PMID- 20133086
TI  - Influence of continuous table motion on patient breathing patterns.
AB  - PURPOSE: To investigate the influence of continuous table motion on patient
      breathing patterns for compensation of moving targets by a robotic treatment
      couch. METHODS AND MATERIALS: Fifteen volunteers were placed on a robotic
      treatment couch, and the couch was moved on different breathing-correlated and 
      uncorrelated trajectories. External abdominal breathing motion of the patients
      was measured using an infrared camera system. The influence of table motion on
      breathing range and pattern was analyzed. RESULTS: Continuous table motion was
      tolerated well by all test persons. Volunteers reacted differently to table
      motion. Four test persons showed no change of breathing range and pattern.
      Increased irregular breathing was observed in 4 patients; however, irregularity
      was not correlated with table motion. Only 4 test persons showed an increase in
      mean breathing amplitude of more than 2mm during motion of the couch. The mean
      cycle period decreased by more than 1 s for 2 test persons only. No abrupt
      changes in amplitude or cycle period could be observed. CONCLUSIONS: The observed
      small changes in breathing patterns support the application of motion
      compensation by a robotic treatment couch.

PMID- 20133087
TI  - Quantitative measurements of the volume and surface area of the radial head.
AB  - PURPOSE: We investigated the hypothesis that a quantitative 3-dimensional
      computed tomography (Q3DCT) modeling technique based on anatomical and
      demographic data that can measure size, shape, and proximal articular surface
      area can be used to develop formulas that could predict the volume and proximal
      surface area of the intact radial head in patients with fractures of the radial
      head. METHODS: We used a consecutive series of 50 computed tomography scans with
      a slice thickness of 1.25 mm or less obtained in patients with fracture of the
      distal humerus, but no injury to the radial head, to create 3-dimensional models.
      The volume and proximal articular surface area of the radial head were measured,
      and predictive formulas based on anatomical measurements and gender were
      calculated using multiple linear regression. RESULTS: There were significant
      correlations between total radial head volume and proximal radial head articular
      surface area for height, weight, radial head diameter, radial neck diameter,
      coronoid diameter, and gender. Multiple linear regression modeling resulted in
      formulas that could account for 89% of the variation in radial head volume and
      75% of the variation in proximal articular surface area. CONCLUSIONS: The volume
      and proximal articular surface area of the radial head can be estimated based on
      anatomical measurements and gender. This may lead to better estimates of lost
      fragments when it is not possible to directly model the fractured radial head and
      computed tomography scan of the opposite limb is not available.

PMID- 20133088
TI  - Congenital pseudarthrosis of the radius treated with gradual distraction and free
      vascularized fibular graft: case report.
AB  - Only 18 cases of congenital radial pseudarthrosis have been reported in the
      English literature; of these, 4 have been treated with free vascularized fibular
      graft. We present a case of a 9-year-old female patient with neurofibromatosis
      type 1 who underwent gradual distraction through the pseudarthrosis site and
      subsequent vascularized fibular grafting for isolated congenital pseudarthrosis
      of her left radius and concomitant longitudinal and angular deformity of the
      wrist joint. At the last follow-up, 10 years postoperatively, the patient has
      maintained bony union, with full wrist flexion-extension and forearm pronation
      supination.

PMID- 20133089
TI  - The cation-uptake regulators AdcR and Fur are necessary for full virulence of
      Streptococcus suis.
AB  - In streptococci, the pleiotropic regulators AdcR and Fur control the transport
      of, zinc and iron, respectively, which are essential components of many proteins.
      In this work, DeltaadcR, Deltafur, and DeltaadcR Deltafur mutants of
      Streptococcus suis, a serious pathogen in pigs and humans, were assayed in a
      mouse model to determine their involvement in the virulence of this bacterium.
      The results showed, for the first time, that the virulence of S. suis mutants
      carrying an inactivation of adcR, fur, or both genes is significantly attenuated
      compared to the wild-type parent strain. Furthermore, all mutants were found to
      be more sensitive to oxidative stress. Our data provide evidence that the adcR
      and fur genes play important roles in the oxidative stress response of S. suis as
      well as in the full virulence of this bacterium.

PMID- 20133090
TI  - Avian influenza virus and Newcastle disease virus (NDV) surveillance in
      commercial breeding farm in China and the characterization of Class I NDV
      isolates.
AB  - In order to determine the actual prevalence of avian influenza virus (AIV) and
      Newcastle disease virus (NDV) in ducks in Shandong province of China, extensive
      surveillance studies were carried out in the breeding ducks of an intensive farm
      from July 2007 to September 2008. Each month cloacal and tracheal swabs were
      taken from 30 randomly selected birds that appeared healthy. All of the swabs
      were negative for influenza A virus recovery, whereas 87.5% of tracheal swabs and
      100% cloacal swabs collected in September 2007, were positive for Newcastle
      disease virus isolation. Several NDV isolates were recovered from tracheal and
      cloacal swabs of apparently healthy ducks. All of the isolates were apathogenic
      as determined by the MDT and ICPI. The HN gene and the variable region of F gene
      (nt 47-420) of four isolates selected at random were sequenced. A 374 bp region
      of F gene and the full length of HN gene were used for phylogenetic analysis.
      Four isolates were identified as the same isolate based on nucleotide sequences
      identities of 99.2-100%, displaying a closer phylogenetic relationship to
      lentogenic Class I viruses. There were 1.9-9.9% nucleotide differences between
      the isolates and other Class I virus in the variable region of F gene (nt 47
      420), whereas there were 38.5-41.2% nucleotide difference between the isolates
      and Class II viruses. The amino acid sequences of the F protein cleavage sites in
      these isolates were 112-ERQERL-117. The full length of HN gene of these isolates
      was 1851 bp, coding 585 amino acids. The homology analysis of the nucleotide
      sequence of HN gene indicated that there were 2.0-4.2% nucleotide differences
      between the isolates and other Class I viruses, whereas there were 29.5-40.9%
      differences between the isolates and Class II viruses. The results shows that
      these isolates are not phylogenetically related to the vaccine strain (LaSota).
      This study adds to the understanding of the ecology of influenza viruses and
      Newcastle disease viruses in ducks and emphasizes the need for constant
      surveillance in times of an ongoing and expanding epidemic of AIV and NDV.

PMID- 20133091
TI  - Mode of delivery affects the bacterial community in the newborn gut.
AB  - The first colonisation of the intestine is one of the most profound immunological
      exposures faced by the newborn and it is influenced by external and internal
      factors. The early composition of human microbiota could have long-lasting
      metabolic effects and the initial composition of human intestinal bacteria is
      also known to affect postnatal immune system development, as we are already aware
      that reduced microbial stimulation during infancy would result in slower
      postnatal maturation of the immune system and development of an optimal balance
      between TH1 and TH2-like immunity. Mode of delivery has a major role on the
      composition of intestinal microbiota in early infancy, as it has been shown that
      infants born by Caesarean section (CS) have lower numbers of Bifidobacteria and
      Bacteroides compared with vaginally born infants. We designed a study to
      investigate the influence of mode of delivery (CS vs. vaginal delivery) on
      intestinal microbial composition on day 3 of life using PCR-denaturing gradient
      gel electrophoresis (DGGE) and PCR-temperature gradient gel electrophoresis
      (TGGE). Both DGGE and TGGE analyses have been used, together with the specific
      amplifications for 10 Bifidobacterium sp., 3 Ruminococcus sp., and Bacteroides
      that all have a highly relevant physiological role in the intestinal ecosystem of
      the newborn. A total of 46 term infants were enrolled in the study, consecutively
      recruiting all the CS-delivered babies (n=23; 8 males and 15 females) and the
      immediately following spontaneously delivered babies (n=23; 11 males and 12
      females). DGGE analysis carried out with Bifidobacterium-specific primers
      revealed the presence of this genus in 13 of 23 (56.5%) samples derived from
      vaginally delivered newborns but in none of the samples obtained from newborns
      delivered by CS. PCR analysis with Bifidobacterium-species-specific primers
      showed that naturally delivered infants had a large number of bifidobacterial
      species, whereas in CS-delivered babies only two samples (8.7%) gave positive
      results, one for B. longum and another for B. gallicum. In all babies enrolled,
      micro-organisms belonging to Ruminococcus species were absent and Bacteroides was
      found in 8.7% of spontaneously delivered babies only. Based on our findings, it
      seems that newborn's intestinal bacteria during the first 3days of life are
      strongly influenced by mode of delivery. The intestinal flora of CS and vaginally
      delivered infants appears to be very different; the former being altered and
      characterised by a substantial absence of Bifidobacteria sp., the latter
      characterised by subject-specific microbial profiles, although predominant groups
      such as B. longum and B. catenulatum could be identified. In summary, mode of
      delivery does affect the early stage of intestinal bacterial colonisation, which
      is altered in CS-delivered infants compared with vaginally delivered infants,
      with only a minor influence of the type of feeding. In addition, the importance
      of methodological aspects for determining intestinal microbiota in clinical
      trials requires emphasis if intestinal microbiota composition is to be considered
      a measure of postnatal adaptation.

PMID- 20133092
TI  - Docosahexaenoic acid (DHA): from the maternal-foetal dyad to the complementary
      feeding period.
AB  - The docosahexaenoic acid (DHA, C22:6n-3) status of infants at birth and maternal
      DHA intake during pregnancy are interconnected and associated with infants'
      developmental performance. High-dosage supplementation of long-chain
      polyunsaturated fatty acids (LCPUFAs; particularly DHA) in mothers, started at
      mid-pregnancy, has been associated with long-term positive effects on
      intelligence quotient scores of neurodevelopment. Poor maternal and infant DHA
      status could partly contribute to the observed association between certain
      conditions and impaired developmental outcome. The dietary DHA enrichment of
      human milk seems to be functionally effective in breastfed infants only when
      lactating mothers start supplementation during pregnancy. Results from trials in
      artificially fed infants are dissimilar and could be related in part to
      uninvestigated covariates such as infant DHA status at birth and the individual
      genetic background. Nevertheless, DHA supplementation during the complementary
      feeding period seems to be effective in improving neurofunctional and visual
      performance.

PMID- 20133093
TI  - [Hyperplastic polyp arising in Barrett's esophagus].

PMID- 20133094
TI  - [Primary pancreatic sarcoma with liver metastases: is there a place for radical
      surgery?].
AB  - Pancreatic leiomyosarcomas are a rare neoplasm that accounts for 1/1000 of
      pancreatic cancers. In the literature, 23 cases of pancreatic leiomyosarcoma have
      been reported and the majority being diagnosed on autopsy. It has never been
      reported any radical curative surgery in presence of synchronous hepatic
      metastasis. We reported a case of a patient affected by a primitive pancreatic
      leiomyosarcoma with bilobar hepatic metastasis, who underwent distal
      splenopancreatectomy associated with the resection of multiple liver metastases.

PMID- 20133095
TI  - Can mammographic assessments lead to consider density as a risk factor for breast
      cancer?
AB  - Admitting that mammographic breast density is an important independent risk
      factor for breast cancer in the general population, has a crucial economical
      health care impact, since it might lead to increasing screening frequency or
      reinforcing additional modalities. Thus, the impact of density as a risk factor
      has to be carefully investigated and might be debated. Some authors suggested
      that high density would be either a weak factor or confused with a masking
      effect. Others concluded that most of the studies have methodological biases in
      basic physics to quantify percentage of breast density, as well as in
      mammographic acquisition parameters. The purpose of this review is to evaluate
      mammographic procedures and density assessments in published studies regarding
      density as a breast cancer risk. No standardization was found in breast density
      assessments and compared density categories. High density definitions varied
      widely from 25 to 75% of dense tissues on mammograms. Some studies showed an
      insufficient follow-up to reveal masking effect related to mammographic false
      negatives. Evaluating breast density impact needs thorough studies with
      consensual mammographic procedures, methods of density measurement, breast
      density classification as well as a standardized definition of high breast
      density. Digital mammography, more effective in dense breasts, should help to re
      evaluate the issue of density as a risk factor for breast cancer.

PMID- 20133096
TI  - Model-based PRFS thermometry using fat as the internal reference and the extended
      Prony algorithm for model fitting.
AB  - A model-based proton resonance frequency shift (PRFS) thermometry method was
      developed to significantly reduce the temperature quantification errors
      encountered in the conventional phase mapping method and the spatiotemporal
      limitations of the spectroscopic thermometry method. Spectral data acquired using
      multi-echo gradient echo (GRE) is fit into a two-component signal model
      containing temperature information and fat is used as the internal reference. The
      noniterative extended Prony algorithm is used for the signal fitting and
      frequency estimate. Monte Carlo simulations demonstrate the advantages of the
      method for optimal water-fat separation and temperature estimation accuracy.
      Phantom experiments demonstrate that the model-based method effectively reduces
      the interscan motion effects and frequency disturbances due to the main field
      drift. The thermometry result of ex vivo goose liver experiment with high
      intensity focused ultrasound (HIFU) heating was also presented in the paper to
      indicate the feasibility of the model-based method in real tissue.

PMID- 20133097
TI  - Improved B(0) field map estimation for high field EPI.
AB  - Echo planar imaging (EPI) is an ultrafast magnetic resonance imaging (MRI)
      technique that allows one to acquire a 2D image in about 100 ms. Unfortunately,
      the standard EPI images suffer from substantial geometric distortions, mainly
      originating from susceptibility differences in adjacent tissues. To reduce EPI
      distortions, correction methods based on a field map, which is a map of the off
      resonance frequencies, have been developed. In this work, a nonlinear least
      squares estimator is used to optimize the estimation of the field map of the B(0)
      field. The model of the EPI and reference data includes parameters for the phase
      evolution, the complex magnitude, the relaxation of the MRI signal and the EPI
      specific phase difference between odd and even echoes, and from these parameters,
      additional corrections might be computed. The reference data required to estimate
      the field map can be acquired with a modified EPI-sequence. The proposed method
      is tested on simulated as well as experimental data and proves to be
      significantly more robust against noise, compared to the previously suggested
      method.

PMID- 20133098
TI  - Application of a bridging ELISA for detection of anti-erythropoietin binding
      antibodies and a cell-based bioassay for neutralizing antibodies in human sera.
AB  - Although erythropoietin (EPO)-related pure red-cell aplasia (PRCA) is a rare
      disorder, attention still needs to be paid because underline mechanism of EPO
      immunogenicity is various and controversial. Among several assay systems for
      screening of anti-EPO binding antibodies (Abs), we adopted and setup the bridging
      ELISA using streptavidin-coated plate. To test their neutralizing activities,
      cell-based neutralizing (NT) bioassay was setup. When we analyzed serum samples
      by using these two assays, we found two positive results in the two samples. In
      the sample 1, 411.9 ng/ml of anti-EPO Abs were found and neutralizing activity of
      36.2% at 1:5 serum dilution was detected. In the sample 2, 40.5 ng/ml of anti-EPO
      Abs were found and neutralizing activity of 96.7% was detected. Our results
      indicate that the higher anti-EPO antibody (Ab) level in a serum does not always
      lead to the stronger neutralizing activity. This report gives crucial
      consideration to the needs of establishing clear criteria to link various assay
      parameters with the onset of PRCA and its progression.

PMID- 20133099
TI  - Photohuperzine A-A new photoisomer of huperzine A: structure elucidation,
      formation kinetics and activity assessment.
AB  - A new photoisomer of the promising "anti-Alzheimer" drug candidate (+/-)
      huperzine A is described. The new substance was formed via a photoisomerization
      reaction and was found to be 1-amino-13-ethylidene-11-methyl-6-aza-tetracyclo
      [7.3.1.0(2.7).0(4.7)]-trideca-2,10-diene-5-one using NMR analysis. The kinetics
      of its formation was studied and proven to be of first-order. The described
      photoisomer showed a significant loss in activity, being more than 100 times less
      active than (-) huperzine A itself. The new substance was named photohuperzine A,
      referring to its photopyridone substructure.

PMID- 20133100
TI  - Acid and base degraded products of ketorolac.
AB  - The stability of ketorolac tromethamine was investigated in acid (0.5M HCl) and
      alkaline conditions (0.5M NaOH), using the same procedure reported by Devarajan
      et al. [2]. The acid and base degradation products were identified by liquid
      chromatography-mass spectrometry (LC-MS).

PMID- 20133101
TI  - Simultaneous measurement of S-warfarin, R-warfarin, S-7-hydroxywarfarin and R-7
      hydroxywarfarin in human plasma by liquid chromatography-tandem mass
      spectrometry.
AB  - Clinically used anticoagulant warfarin is usually available as a racemic mixture
      of S- and R-warfarin that are both metabolized mainly by cytochrome P450
      isoenzymes. Determination of warfarin enantiomers and their enantiomeric 7
      hydroxywarfarin (7-OH-warfarin) metabolites in the human plasma sample allows
      probing of cytochrome P450 isoenzyme activities and detection of ingestion of
      warfarin-containing products for the investigation of unexplained bleeding. The
      present study aims to develop a sensitive and specific liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method for simultaneous detection of S
      warfarin, R-warfarin, S-7-OH-warfarin and R-7-OH-warfarin in human plasma. Plasma
      samples were extracted with mixed-mode cation-exchange (MCX) cartridge with
      recoveries of greater than 87.0% for all four analytes. The selectivity of 7-OH
      warfarin from other monohydroxylated warfarin metabolites such as 4'-, 6-, 8- and
      10-hydroxywarfarins using a Chirobiotic V chiral column and multiple reaction
      monitoring (MRM) was addressed. The developed LC-MS/MS method is simple, specific
      and has been fully validated with satisfactory accuracy and adequate
      reproducibility with limit of quantification (LOQ) of 5 ng/ml for all four
      analytes. The method was successfully applied to analyze the steady state plasma
      concentrations of the four analytes in 30 patients.

PMID- 20133102
TI  - Prevention and sporadic carbon monoxide poisoning related to shisha (hookah,
      narghile) tobacco smoking.

PMID- 20133103
TI  - Violence in the emergency department: a national survey of emergency medicine
      residents and attending physicians.
AB  - BACKGROUND: Violence in the Emergency Department (ED) is a well-known phenomenon.
      Few studies have been done to assess the incidence and nature of violence in the
      ED. STUDY OBJECTIVES: The purpose of this study was to assess the incidence of
      violence in the ED nationwide. METHODS: This study was a prospective, cross
      sectional online survey of Emergency Medicine (EM) residents and attending
      physicians. Of the 134 accredited United States (US) EM residency programs, 65
      programs were randomly selected and invited to participate. RESULTS: Overall, 272
      surveys were returned, of which 263 (97%) were completed and further analyzed. At
      least one workplace violence act in the previous 12 months was reported by 78%
      (95% confidence interval 73-83%) of respondents, with 21% reporting more than one
      type of violent act. Workplace violence was experienced similarly between males
      and females (79% vs. 75%, respectively; p = 0.65), and was more common in EDs
      with annual volumes over 60,000 patients (82% vs. 67%; p = 0.01). The most common
      type of workplace violence was verbal threats (75%) followed by physical assaults
      (21%), confrontations outside the workplace (5%), and stalking (2%). Security was
      available full time in most settings (98%), but was least likely to be physically
      present in patient care areas. The majority of respondent EDs did not screen for
      weapons (40% screened) or have metal detectors (38% had metal detectors). Only
      16% of programs provided violence workshops, and less than 10% offered self
      defense training. CONCLUSION: Despite the high incidence of workplace violence
      experienced by the emergency physicians who responded to our survey, less than
      half of these respondents worked in EDs that screened for weapons or had metal
      detectors. An even smaller number of physicians worked in settings that provided
      violence workshops or self-defense training.

PMID- 20133104
TI  - Anti-Cytokeratin (CAM5.2) reagent directed against cytokeratin 8, not cytokeratin
      18. Comment on "Improving staging accuracy in colon and rectal cancer by sentinel
      lymph node mapping: a comparative study. Eur J Surg Oncol. 2009; 35: 1065-1070.".

PMID- 20133105
TI  - An unusual case of pigmented villonodular synovitis 14 years after total hip
      arthroplasty.
AB  - Pigmented villonodular synovitis (PVNS) is a rare benign proliferation lesion of
      the synovium of the joint, bursa, and the tendon sheath. We report here a case of
      PVNS in a 78-year-old woman 14 years after she underwent total arthroplasty of
      her right hip. Diffuse PVNS was detected in her right hip during surgery to
      replace her prosthesis, which had loosened. Macroscopically, the surface of the
      resected tissue was black and composed of papillae and nodules. Histologically,
      the tissue consisted of proliferative synoviocytes with black pigment in the
      cytoplasm. Beneath the synoviocytes were foamy cells. Pathologic analysis
      confirmed the diagnosis of PVNS with black pigment and the presence of
      hemosiderin. This indicates that implantation of the prosthesis might have caused
      the lesion or might have caused its proliferation.

PMID- 20133106
TI  - Epileptic negative myoclonus: a combined study of EEG and [123I]iomazenil (123I
      IMZ) single photon emission computed tomography indicating involvement of medial
      frontal area.
AB  - Negative myoclonus (NM) is a sudden brief atonia in muscle that causes jerky
      lapses of posture. This study employed an electrophysiological technique (silent
      period-locked-averaging (SPLA) electroencephalography (EEG)) and a
      pharmacodynamic imaging technique (123I-IMZ-SPECT) to examine epileptic NM (ENM).
      Delayed-phase 123I-IMZ-SPECT images, which reflect the specific binding of the
      tracers to GABA-A receptors, exhibited significant decrease in the left medial
      frontal area. The deficit in GABA-A receptors indicated that abnormal
      synchronization was mediated by the lack of inhibitory postsynaptic mechanism.
      The SPLA-EEG recorded spike-like notches superimposed on the slope of negative
      slow activity in the contralateral fronto-central region. The slow activity
      started around 100 ms before and the peak of the spike-like component was 30 ms
      before the onset of ENM. Since the 123I-IMZ-SPECT shows the actual distribution
      of the tracers, the abnormal area associated with ENM in this particular patient
      was supposed to be on the left medial frontal lobe. Scalp EEG, though it cannot
      always accurately locate the abnormal area, was highly sensitive to be able to
      detect electrical activities transmitted through neuronal network or volume
      conductor. Combined use of the two methods provided high resolution both in
      spatial and temporal domain.

PMID- 20133107
TI  - Processing of facial configuration in individuals at ultra-high risk for
      schizophrenia.
AB  - BACKGROUND: Discrepancies in the ability to recognize faces constitute an
      important aspect of the impaired social cognitive abilities of patients with
      schizophrenia. Previous studies have suggested that specific problems with the
      processing of facial configuration affect the face-recognition deficit in
      patients with schizophrenia. However, little is known about whether these
      deficits in face recognition are present before the onset of schizophrenia.
      METHOD: This study compared performances on a face processing task among three
      groups: individuals at ultra-high risk for schizophrenia (n=20), patients with
      schizophrenia (n=18), and normal controls (n=20) using a face-discrimination task
      involving pairs of photographs depicting upright and inverted images with
      changing features and configurations. Chair stimuli were used as the control
      task. RESULTS: The individuals at ultra-high risk for schizophrenia performed
      more poorly than did normal controls with regard to the processing of facial
      configuration but not the facial feature and did not differ significantly from
      the patients with schizophrenia with regard to the processing of facial
      configuration and upright facial features. CONCLUSION: This study suggests that a
      specific dysfunction in the processing of facial configuration, which has an
      impact on face recognition, might be present before and deteriorate in patients
      with schizophrenia. Deficits in face recognition among individuals at risk for
      psychosis might contribute significantly to the social dysfunction associated
      with schizophrenia.

PMID- 20133108
TI  - How much more effective do depot antipsychotics have to be compared to oral
      antipsychotics before they are prescribed?
AB  - Antipsychotic depots are less frequently prescribed than oral compounds. In an
      experimental study involving N=106 psychiatrists we studied how much more
      effective with respect to relapse prevention depot antipsychotics have to be
      compared to oral antipsychotics before they are chosen for prescription. Most
      psychiatrists have to judge depot as clearly superior with respect to relapse
      prevention before they recommend it to patients. If psychiatrists judge depot as
      unpleasant for the patients and do not see much need for checking their patients'
      compliance they are less likely to prescribe depot. Other psychiatrist-related
      factors (e.g. age, gender, and work experience) did not influence attitudes
      toward depot.

PMID- 20133109
TI  - 1H, 13C and 31P MAS NMR studies of lyophilized brain tumors.
AB  - (1)H, (13)C and (31)P magic angle spinning magnetic resonance spectra (MAS NMR)
      of lyophilized brain tissue specimens were recorded. Among the 35 cases of brain
      tumors there were 24 glioblastomas, seven meningiomas and a few other types. (1)H
      NMR measurements were performed with a MAS speed of 33 kHz. The intense CH(3),
      CH(2) and CH peaks in the (1)H spectrum result from fatty acid residues of
      phospholipids, which are "mobile enough" besides the anhydrous environment. (13)C
      CPMAS spectra revealed the resonances of creatine and guanidine carbons; the high
      intensity signals arise from carbonyl groups and methylene carbons of lipids. In
      particular we found a fraction of mobile lipids, characterized by narrow
      resonances and long T(1rho)(H) Overlapped resonances of phospholipids head groups
      contributed to the peak at 4-7 ppm in the (31)P MAS NMR spectra. Our results
      indicate that (1)H and (13)C MAS NMR are able to characterize tumor types:
      differentiate glioblastomas from meningiomas and shed light on tumor biochemical
      characteristics. However, water soluble metabolites are not observed and
      macromolecules yield broad overlapped resonances. Generally, lyophilization
      significantly decreases discriminative potential of NMR analysis.

PMID- 20133110
TI  - Do food microemulsions and dietary mixed micelles interact?
AB  - Using microemulsions (ME) as delivery vehicles requires understanding whether
      water-insoluble molecules are delivered by an interaction of the ME system with
      the dietary mixed micelles (DMM) in the small intestine to give new mixed
      micelles, or by alternate paths. Diluted DMM and ME systems were mixed at various
      weight ratios to address this question. The individual and mixed systems were
      characterized by physical techniques that address this interaction from different
      aspects. This research showed that increased DMM concentration in ME/DMM mixed
      systems caused: (1) increased conformational order of the acyl chains and
      perturbed hydrogen bonds between the ethoxylate headgroups (based on ATR-FTIR
      results); (2) significant increase in microviscosity (from 1.7 to 3.3ns) (based
      on EPR results); (3) increased diffusivity of the surfactant molecules compared
      to their diffusivity in pure ME droplets, and decreased diffusivity of the
      taurochenodeoxycholate molecules compared to their diffusivities in pure DMM
      micelles (based on PGSE-NMR results); (4) formation or modification of
      intramolecular interactions (based on NOESY-NMR results); (5) decreased average
      droplet diameter and increased droplet density per unit area compared to pure ME
      systems (based on DLS and cryo-TEM results); and (6) fluorescence resonance
      energy transfer between two dyes (diphenylhexatriene and Nile Red), which were
      solubilized in each system separately (based on fluorescence resonance energy
      transfer results). These results show that DMM and ME interact to create ME-DMM
      mixed micelles, providing a potential pathway for delivering solubilized
      molecules.

PMID- 20133111
TI  - Influence of ionic strength changes on the structure of pre-adsorbed salivary
      films. A response of a natural multi-component layer.
AB  - Salivary films coating oral surfaces are critically important for oral health.
      This study focuses on determining the underlying nature of this adsorbed film and
      how it responds to departures from physiological conditions due to changes in
      ionic strength. Under physiological conditions, it is found that pre-adsorbed in
      vitro salivary film on hydrophobic surfaces is present as a highly hydrated
      viscoelastic layer. We follow the evolution of this film in terms of its
      effective thickness, hydration and viscoelastic properties, as well as adsorbed
      mass of proteins, using complementary surface characterisation methods: a Surface
      Plasmon Resonance (SPR) and a Quartz Crystal Microbalance with Dissipation
      Monitoring (QCM-D). Our results support a heterogeneous model for the structure
      of the salivary film with an inner dense anchoring layer and an outer highly
      extended hydrated layer. Further swelling of the film was observed upon
      decreasing the salt concentration down to 1mM NaCl. However, upon exposure to
      deionised water, a collapse of the film occurs that was associated with the loss
      of water contained within the adsorbed layer. We suggest that the collapse in
      deionised water is driven by an onset of electrostatic attraction between
      different parts of the multi-component salivary film. It is anticipated that such
      changes could also occur when the oral cavity is exposed to food, beverage, oral
      care and pharmaceutical formulations where drastic changes to the structural
      integrity of the film is likely to have implications on oral health, sensory
      perception and product performance.

PMID- 20133112
TI  - Optimizing Au-nanoprobes for specific sequence discrimination.
AB  - Gold nanoparticles functionalized with thiol-oligonucleotides are ideal platforms
      for detection of specific DNA sequences. Here we evaluate the effect of single
      base mismatches in hybridization efficiency according to the position of the
      mismatch, base pairing combination and thiol-oligonucleotide density in terms of
      specificity and efficiency of target recognition. Hybridization efficiency and
      single-nucleotide polymorphism discrimination at room temperature is maximized at
      a density of 83+/-4 thiol-oligonucleotides per 13.5 nm gold nanoparticle (24
      pmol/cm(2)), and when the mismatch is localized at the 3'-end of the Au
      nanoprobe, i.e. away from the gold nanoparticle surface.

PMID- 20133113
TI  - Structure and viscoelastic behavior of pharmaceutical biocompatible anionic
      microemulsions containing the antitumoral drug compound doxorubicin.
AB  - Structure and viscoelastic properties of negatively charged oil-in-water (o/w)
      microemulsions have been investigated. Microemulsions (ME) containing soya
      phosphatidylcholine (SPC), eumulgin HRE 40 (EU) and sodium oleate (SO) as
      surfactant, cholesterol (CHO) as oil phase, and aqueous buffer with and without
      the antitumoral doxorubicin (DOX) have been studied. The effect of the oil
      phase/surfactant ratio (O/S) and the DOX incorporation on the structural and
      rheological properties have been studied in several compositions of ME systems.
      The rheological analyses were performed through the oscillation stress sweep,
      creep recovery test, and viscosity test. The combination of the DOX incorporation
      with the high O/S ratio provided a further viscoelastic structure with linear
      behavior. Independently of the O/S ratio the oil phase diameter increases
      according to a sigmoid profile, stabilizing up to 340 min. The apparent viscosity
      decreases a minimum value with the shear rate, but increases with both the O/S
      ratio and the DOX incorporation in the system. The structural and rheological
      properties of the studied MEs were directly dependent on the O/S ratio and can be
      used to improve the application of the system in the pharmaceutical field.

PMID- 20133114
TI  - [Incidence of Cryptosporidium sp in infantile acute gastroenteritis].

PMID- 20133115
TI  - [Early language assessment and therapy].
AB  - A child's functional language develops during his first three years as a part of
      its general development (motor, senses, affection and cognition) based upon
      components of non-verbal communication and progressive learning of phonological,
      lexical and syntactic capabilities, first from a receptive then from an
      expressive side. When difficulties in the development of a child are observed,
      the assessment of its capacity of non-verbal communication and understanding
      allows defining the necessary conditions to install an oral language. Secondly,
      the speech therapist evaluates the level of the language of the child compared to
      other parts of its development (are the deviations compared to standards,
      observed using development scales, homogeneous between applications?). The
      interdisciplinary assessment is necessary. The installation of communication,
      being the exchange with a person using an object, a situation or a need and the
      development of the verbal understanding, related to the experience of the child,
      are precursory to oral productions. Precocious requests of language functions
      (using questions, comments, stories, dialogue...), using plays adapted for every
      individual child, giving support to parents, allows to prevent difficult behavior
      caused by the frustration due to the impossibility to express himself. Waiting
      for a child with difficulties to talk before a speech therapist's intervention
      means taking the risk to react too late to correct verbal communication troubles,
      with possible repercussions on the person's autonomy.

PMID- 20133116
TI  - [Complications of bacterial rhino-sinusitis in children: a case report and a
      review of the literature].
AB  - Acute sinusitis in children is a controversial issue in terms of its diagnostic
      criteria, classification and therapeutic management. A therapeutic delay can lead
      to complications if the cause is bacterial. Guidelines have been set, but they
      are not consensual in pediatrics. Complications of acute bacterial sinusitis are
      uncommon in children, but they can be extremely severe and cause high morbidity
      and mortality. Because of their rarity, they often are not identified early,
      exposing the patient to an unfavorable outcome. We report on a case of acute
      bacterial pan-sinusitis complicated with thrombophlebitis of the cavernous
      sinuses and meningitis in a 9-year-old child, in spite of early and adapted
      antibiotic therapy. The bacterial agent was Staphylococcus aureus, which had no
      resistance or toxin profile. The progression was favorable under intravenous
      antibiotic therapy and after bilateral sphenoidectomy. This case raises the
      question of the best therapy for acute bacterial sinusitis in pediatrics and the
      management of complications.

PMID- 20133117
TI  - Downregulation of cyclin D1 is associated with decreased levels of p38 MAP
      kinases, Akt/PKB and Pak1 during chemopreventive effects of resveratrol in liver
      cancer cells.
AB  - Resveratrol is a naturally occurring phytoalexin with antioxidant activity. The
      chemopreventive effects of resveratrol against various types of cancer are well
      known, though the underlying molecular mechanisms of its action are still not
      identified. Hepatocellular carcinoma (HCC) is a one of the most lethal
      malignancies and there is no effective treatment till date. It is known that
      cyclin D1 is overexpressed in liver cancers. Accordingly we have studied the
      chemopreventive effects of resveratrol on cyclin D1 expression and the signaling
      pathways that regulate cyclin D1 in HepG2 cells. Flow cytometry and PCNA western
      blot data showed that resveratrol inhibits proliferation of HepG2 cells. Also,
      resveratrol treatment downregulated cyclin D1 as well as p38 MAP kinase, Akt and
      Pak1 expression and activity in HepG2 cells, suggesting that growth inhibitory
      activity of resveratrol is associated with the downregulation of cell
      proliferation and survival pathways. Furthermore, resveratrol treated cells
      showed increase in ERK activity suggesting possible sensitization to apoptosis.
      Thus in the present study, we report a three-dimensional relationship between the
      growth inhibitory effects of resveratrol - decrease in the levels of cyclin D1 -
      and downregulation of cell proliferation and survival pathways in HepG2 cells
      leading to cellular degenerative changes. These observations suggest that
      resveratrol has good potential as effective chemopreventive agent against liver
      cancer and warrant further studies.

PMID- 20133118
TI  - Briquetting of charcoal from sugar-cane bagasse fly ash (scbfa) as an alternative
      fuel.
AB  - Brazil is the largest worldwide producer of alcohol and sugar from sugar-cane and
      has an extensive alternative program for car fuel which is unique. The objective
      of this work is to offer one management option of a solid residue produced by
      this industrial segment. The pressed sugar-cane bagasse is burned to produce
      steam and electricity by cogeneration. The combustion yields both bottom and fly
      ashes which contain high amounts of silicon oxide as a major component. Fly ash
      which contains a high volume (>30% by weight) of charcoal was used in this work.
      The ash was sieved to separate the thick charcoal from inorganic materials which
      are concentrated in the thinner fraction. The briquettes were hand pressed using
      charcoal mixed with a binder (starch) obtained from cassava flour (a tropical
      root). The results (density, mechanical resistance) obtained with 8% by weight of
      starch binder are presented here. Thermogravimetric analysis (TGA) and
      differential scanning calorimetry (DSC) were used to characterize the ashes and
      the briquettes. The results show that sugar-cane bagasse fly ash (SCBFA) can be
      used to produce briquettes with an average density of 1.12gcm(-3) and an average
      calorific value of 25,551kJ/kg.

PMID- 20133119
TI  - Compensation effect during the pyrolysis of tyres and bamboo.
AB  - Pyrolysis parameters (e.g. pre-exponential factor A, and activation energy E) of
      two waste materials, namely, tyre rubber and bamboo scaffolding, based on the
      Arrhenius equation were obtained from weight loss data via thermogravimetry at
      different heating rates. The compensation effect, which suggests that the linear
      variation in the pre-exponential factor and the activation energy, was observed
      for these materials. This can be attributed to the variety of active sites over
      the reactant surface in the course of decomposition. The calculated data from
      several revised, first-order models were compared with similar models in the
      literature. It has been shown that both literature and our calculated data
      exhibit high linearity in terms of lnA and E, revealing that the latter agree
      well with other researchers' work.

PMID- 20133120
TI  - A case report on the effect of fan beam thickness in helical tomotherapy of
      nasopharyngeal carcinoma.
AB  - The fan beam thickness (FBT) in helical tomotherapy is defined by a pair of
      collimators parallel to the rotational orbit of the radiation beam and is fixed
      for a specific patient treatment. The aim of this case study is to evaluate the
      dosimetric influence of changing the FBT in the treatment of a nasopharyngeal
      carcinoma (NPC) patient. The subject was a T2N1M0 stage NPC patient. The planning
      target volumes (PTVs) of the primary nasopharyngeal tumor and the left and right
      cervical lymphatics were delineated along with the organs at risk (OARs) in the
      corresponding computed tomography slices. Three treatment plans with FBT of 1.0
      cm, 2.5 cm, and 5.0 cm (FBT-10, FBT-25, and FBT-50) were generated separately
      based on similar dose constraints and planning parameters. The dosimetric results
      of the PTV and OARs were collected and compared among the 3 treatment plans. The
      differences in the dose parameters of the PTVs were small among the 3 plans. The
      FBT-10 plan demonstrated the most homogeneous PTV doses with the smallest
      homogeneity indices (HIs). The FBT-50 plan delivered the highest dose to the OARs
      and the FBT-10 plan delivered the lowest. The differences between the 2 plans
      were more significant in the spinal cord, optic chiasm, optic nerves, and lens.
      This case study demonstrated that the variation of FBT in tomotherapy affected
      the quality of the treatment plan mainly in the OAR doses, but not so much in the
      PTV. Increasing the FBT reduced the effectiveness in the sparing of OARs.

PMID- 20133121
TI  - Rise of the molecular machines.

PMID- 20133122
TI  - Structure-based design of kinetic stabilizers that ameliorate the transthyretin
      amyloidoses.
AB  - Small molecules that bind to normally unoccupied thyroxine (T(4)) binding sites
      within transthyretin (TTR) in the blood stabilize the tetrameric ground state of
      TTR relative to the dissociative transition state and dramatically slow tetramer
      dissociation, the rate-limiting step for the process of amyloid fibril formation
      linked to neurodegeneration and cell death. These so-called TTR kinetic
      stabilizers have been designed using structure-based principles and one of these
      has recently been shown to halt the progression of a human TTR amyloid disease in
      a clinical trial, providing the first pharmacologic evidence that the process of
      amyloid fibril formation is causative. Structure-based design has now progressed
      to the point where highly selective, high affinity TTR kinetic stabilizers that
      lack undesirable off-target activities can be produced with high frequency.

PMID- 20133123
TI  - Cytotoxic, apoptotic and antioxidant activity of the essential oil of Amomum tsao
      ko.
AB  - The antioxidant activity, cytotoxicity and mechanism of induction of HepG2 cell
      death of essential oil from Amomum tsao-ko were determined. The essential oil was
      cytotoxic to HepG2, Hela, Bel-7402, SGC-7901 and PC-3 cell lines. The lowest
      IC(50) of 31.80+/-1.18microg/ml was measured for HepG2 carcinoma cell lines. The
      IC(50) for normal human cell lines (HUVEC and HL-7702) was 163.91+/-5.11-272.41+/
      0.97microg/ml. Analyses by flow cytometry, Hoechst 33258 staining and agarose gel
      electrophoresis indicated that the essential oil induced apoptosis. The essential
      oil has weak antioxidant activity as measured by 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radical assay, thiobarbituric acid (TBA) test and ferric reducing
      antioxidant power (FRAP) assay. The data suggest that the essential oil of A.
      tsao-ko could be a potential medicinal resource.

PMID- 20133124
TI  - Presence of zoonotic pathogens in physico-chemically characterized manures from
      hog finishing houses using different production systems.
AB  - Hog production has been intensified in Eastern Canada, by 50% over the last
      20years. Wastes are now managed with conventional production systems (slatted
      floor), litter systems or source separation systems. We studied the presence of
      total and fecal coliforms, Campylobacter, Clostridium perfringens, Enterococcus,
      Escherichia coli, Salmonella, Yersinia enterocolitica, Giardia and
      Cryptosporidium in the manure of all of these production systems. The
      concentrations of the studied zoonotic pathogens did not differ between the
      conventional and the litter systems investigated. The source separation system
      yielded separated solid and liquid fractions. Total and fecal coliforms, C.
      perfringens, Enterococcus, E. coli, and Y. enterocolitica were found in the
      solids and the liquid fractions of a source separation system.Campylobacter
      species were not detected in the liquid fractions. Zoonotic pathogens are
      therefore, found in the manure of Eastern Canadian hog finishing houses equipped
      either with conventional, sawdust litter or source separation systems. Pathogens
      inactivation will require changes in manure management practices or the use of
      manure disinfection methods.

PMID- 20133125
TI  - Characteristics and humidity control capacity of activated carbon from bamboo.
AB  - Activated carbons were prepared from bamboo by chemical activation with K2CO3 or
      physical activation with CO2. The structural and surface chemical characteristics
      of the activated carbons were determined by N2 adsorption-desorption and Boehm
      titration, respectively. The water vapor adsorption properties of the activated
      carbons with various pore structures (preparation conditions) were examined. The
      relationship between water vapor adsorption capacity and pore properties, and the
      humidity control capacity of the prepared activated carbons are also discussed.
      The water adsorption isotherms show a region of rapidly increasing uptake of
      water vapor, and the relative humidity corresponding to those regions was
      different according to the preparation conditions, especially activation
      temperature. Water vapor adsorption capacity was improved with larger pore volume
      and surface area, but the humidity control capacity in a certain specific
      humidity region differed greatly according to the relative humidity corresponding
      to the steeply rising regions of the isotherms. In the typical operating
      conditions of an adsorption heat pump, RH 10-35%, the bamboo-sourced activated
      carbon that was prepared at 873K by potassium carbonate activation with
      impregnation ratio 1.0 had the highest humidity control capacity.

PMID- 20133126
TI  - High-rate anaerobic degradation of 5 and 6 carbon sugars under thermophilic and
      mesophilic conditions.
AB  - In this research paper, a comparison between thermophilic and mesophilic
      anaerobic degradation of a variety of the simple sugar components of carbohydrate
      rich biomass is presented. In order to investigate the degradability of these
      basic sugars, three synthetic sugar based influents were supplied to two high
      rate upflow anaerobic hybrid reactors (UAHR) operated at 37 degrees C (R1) and 55
      degrees C (R2). These influent streams were: d-glucose/sucrose; l-arabinose/d
      xylose and l-rhamnose/d-galacturonic acid. The reactors were challenged in terms
      of influent composition rather than loading rate and were therefore operated at a
      maximum volumetric loading rate (VLR) of 4.5 gCODl(-1)d(-1) during stable reactor
      performance. It was found that a switch from a d-glucose/sucrose synthetic
      influent to an influent composed of l-arabinose/d-xylose resulted in failure of
      the mesophilic reactor while the thermophilic UAHR was able to tolerate the
      change of sugar influent at an unchanged VLR of 4.5 gCODl(-1)d(-1). A subsequent
      phasing-in approach was used to introduce new sugar influent streams and proved
      highly successful. The physiology of the biomass was assessed and it was noted
      that thermophilic anaerobic digestion (AD) involved the formation of acetate and
      H(2), implying the involvement of homoacetogenic bacteria, while mesophilic AD
      proceeded via the formation of other intermediates.

PMID- 20133127
TI  - Identification and characterization of genes conferring salt tolerance to
      Escherichia coli from pond water metagenome.
AB  - Metagenomics provides culture-independent access to gene pool of the whole
      microbial communities. To identify genes responsible for salt tolerance in
      unculturable bacteria, Escherichia coli clones were enriched with an ability to
      grow at inhibitory NaCl concentrations (750mM) from a pond water metagenomic
      library. From two unique clones, genes encoding for proteins with similarity to a
      putative general stress protein (GspM) harbouring GsiB domain and a putative
      enoyl-CoA hydratase (EchM) were identified to be responsible for salt tolerance.
      The gspM was expressed by its native promoter whereas the echM was expressed from
      the lacZ promoter of the plasmid. EchM was overexpressed with a hexahistidyl tag.
      Purified EchM showed crotonyl-CoA hydratase activity. These genes have potential
      application in generating salt tolerant recombinant bacteria or transgenic
      plants.

PMID- 20133128
TI  - Removal of cyanobacterial bloom from a biopond-wetland system and the associated
      response of zoobenthic diversity.
AB  - Harmful cyanobacterial bloom in water bodies frequently occurs due to
      eutrophication, leading to the excessive growth of cyanobacteria which in turn
      may lead to a decrease in biodiversity. A biopond-wetland system to control
      cyanobacterial bloom and stabilize or even increase biodiversity is proposed and
      applied in a pond, Kunming, western China where cyanobacterial blooms frequently
      break out. The biopond-wetland system examined includes three main parts: filter
      feeding fish, replanted pond macrophytes, and a terminal artificial wetland. When
      the hydraulic load of the biopond-wetland system was 500m(3)/d on non-rainy days,
      the system successfully decreased the level of chlorophyll-a (Chl-a). The
      declining levels of total nitrogen (TN), total phosphorus (TP) and ammonia in the
      water after establishing the biopond-wetland system also coincided with the
      disappearance of the cyanobacterial bloom. In the second summer, when the biopond
      wetland system was in a relatively steady-state condition, the overall average
      nutrient removal efficiencies were as follows, Chl-a (83%), TN (57%), TP (70%)
      and ammonia (66%), while in the second winter, the overall average removal
      efficiencies were Chl-a (66%), TN (40%), TP (53%) and ammonia (49%). Simpson's
      diversity index of zoobenthos indicated that the system increased the zoobenthic
      diversity and improved the growth conditions of the zoobenthos habitat. The
      results demonstrated that the biopond-wetland system could control cyanobacterial
      blooms.

PMID- 20133129
TI  - Expression and characterization of Bacillus licheniformis chitinase (ChiA),
      suitable for bioconversion of chitin waste.
AB  - Chitinase (EC 3.2.1.14) is an enzyme with multiple industrial applications. These
      include bioconversion of chitin waste, a highly resistant and abundant biopolymer
      from crustacean food industry, into glucosamine and chito-oligosaccharide value
      added products. This paper reports on the expression of endochitinase (ChiA) from
      Bacillus licheniformis strain DSM8785 in E. coli and characterization of the
      recombinant enzyme. Recombinant ChiA could efficiently convert colloidal chitin
      to N-acetyl glucosamine and chitobiose at pH 4.0, 6.0 and 9.0 at 50 degrees C and
      retained its activity up to 3days under these conditions, suggesting that this
      enzyme is suitable for bioconversion of chitin waste.

PMID- 20133130
TI  - Determination of Eucalyptus spp lignin S/G ratio: a comparison between methods.
AB  - The syringyl/guaiacyl ratio was determined for six different Eucalyptus spp. wood
      clones cultivated in four regions in Brazil. The determinants were made by
      pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) and the results were
      compared with those obtained by alkaline nitrobenzene oxidation method. The S/G
      ratios were obtained considering all the identified lignin derivatives in the
      pyrograms and also using two groups of markers. The first group of markers
      consisted of guaiacol, 4-methylguaiacol, 4-vinylguaiacol, trans-isoeugenol,
      syringol, 4-methylsyringol, 4-vinylsyringol and trans-4-propenylsyringol
      compounds as markers. The second group included guaiacol, 4-methylguaiacol, 4
      vinylguaiacol, vanillin, 4-ethylsyringol, 4-vinylsyringol, syringaldehyde,
      syringylacetone and trans-4-propenylsyringol. It was observed from the
      statistical analysis that the values of S/G obtained by Py-GC-MS using the two
      groups of markers did not differ significantly from those obtained by
      nitrobenzene oxidation method.

PMID- 20133131
TI  - Utilization of protein extract from dairy manure as a nitrogen source by Rhizopus
      oryzae NRRL-395 for l-lactic acid production.
AB  - Six levels of crude protein (0.21, 0.42, 0.84, 1.68, 2.52, and 3.36g/L) and six
      levels of protein hydrolysates from dairy manure, defined by degree of hydrolysis
      (DH, 6.9%, 17.2%, 25.9%, 33.8%, 36.1%, and 36.7%), were investigated as the
      nitrogen source for production of l-lactic acid by Rhizopus oryzae NRRL-395 with
      respect to the influence of nitrogen source on l-lactic acid yield and the
      correlation with biomass yield and mycelia morphology. Increases in crude protein
      from 0.21 to 1.68g/L led to an increase in l-lactic acid concentration in the
      culture media from 6.48 to 57.7g/L. However, further increases beyond 1.68g/L did
      not present continuing increases in l-lactic acid yields. The highest biomass
      yield was obtained at a crude protein nitrogen concentration of 2.52g/L.
      Hydrolysates with high DH resulted in high yields of l-lactic acid and biomass.
      At a nitrogen level of 0.42g/L (hydrolysates) with DH ranging from 33.8% to
      36.7%, the l-lactic acid yield of 0.53-0.56g/g of glucose was achieved, coupled
      with a 13-14% yield of fungal biomass.

PMID- 20133132
TI  - Properties of sugarcane waste-derived bio-oils obtained by fixed-bed fire-tube
      heating pyrolysis.
AB  - Agricultural waste in the form of sugarcane bagasse was pyrolyzed in a fixed-bed
      fire-tube heating reactor under different pyrolysis conditions to determine the
      role of final temperature, sweeping gas flow rate and feed size on the product
      yields. Final temperature range studied was between 375 and 575 degrees C and the
      highest liquid product yield was obtained at 475 degrees C. Liquid products
      obtained under the most suitable conditions were characterized by physical
      properties, elemental analysis, GCV, FT-IR, (1)H NMR analysis and distillation.
      The empirical formula of the bio-oil with heating value of 23.5MJ/kg was
      established as CH(1.68)O(0.557)N(0.012). Comparison with other approaches showed
      that the liquid product yield by this simpler reactor system was higher with
      better physico-chemical properties as fuel. These findings show that fixed-bed
      fire-tube heating pyrolysis is a good option for production of bio-oils from
      biomass solid wastes.

PMID- 20133133
TI  - Desmin myopathy with severe cardiomyopathy in a Uruguayan family due to a codon
      deletion in a new location within the desmin 1A rod domain.
AB  - Desmin myopathy is a heterogeneous neuromuscular disorder characterized by
      skeletal myopathy and cardiomyopathy, inherited mostly in an autosomal dominant
      pattern. We report a five generation Uruguayan family with severe cardiomyopathy
      and skeletal myopathy. Its most striking features are: atrial dilation,
      arrhythmia, conduction block and sudden death due to conduction impairment.
      Affected skeletal muscle shows alteration of mitochondria with paracrystallin
      inclusions and granulofilamentous material scattered in the muscle fibres. This
      family carries an unusual deletion p.E114del within the 1A rod domain of desmin.
      Transfected cells expressing the mutated desmin show punctuated and speckled
      cytoplasmic aggregates. The mutation causes a local conformational change in
      heptads a/d residues and charge positions. These findings lead to the hypothesis
      that coiled-coil interactions may be impaired, resulting in severe alterations in
      the desmin network. This is the first time that a mutation affecting this domain
      in the desmin molecule is described in a desminopathy.

PMID- 20133134
TI  - ADF/cofilin: a functional node in cell biology.
AB  - Recent findings have significantly expanded our understanding of the regulation
      of actin-depolymerizing factor (ADF)/cofilin proteins and the profound
      multifaceted impact that these well-established regulators of actin dynamics have
      on cell biology. In this review we discuss new aspects of previously documented
      regulation, such as phosphorylation, but also cover novel recently established
      modes of regulation and functions of ADF (also known as destrin)/cofilin. We now
      understand that their activity responds to a vast array of inputs far greater
      than previously appreciated and that these proteins not only feed back to the
      crucially important dynamics of actin, but also to apoptosis cascades,
      phospholipid metabolism, and gene expression. We argue that this ability to
      respond to physiological changes by modulating those same changes makes the
      ADF/cofilin protein family a homeostatic regulator or 'functional node' in cell
      biology.

PMID- 20133135
TI  - Anthropometric measurements of knee joints in Thai population: correlation to the
      sizing of current knee prostheses.
AB  - Anthropometric data on the distal femoral condyle and the proximal tibia of 200
      knees in 200 Thai subjects were measured using magnetic resonance imaging (MRI).
      The data including the resected femoral anterior-posterior (AP) length, the
      resected femoral medial-lateral (ML) width, the resected tibial AP length and the
      resected tibial ML width were measured. A characterization of the aspect ratio
      (the ML to AP dimensions) was made for the distal part of the femur and the
      aspect ratio (the AP to ML dimensions) was made for the proximal part of the
      tibia. All parameters were compared to the size of the total knee prosthesis with
      four prosthetic systems which currently used in Thailand: NexGen (Zimmer), P.F.C.
      Sigma (Depuy-Johnson & Johnson), Genesis II (Smith & nephew), and Scorpio
      (Stryker). The results of this study could provide fundamental data for the
      design of knee prostheses suitable for the Thai population.

PMID- 20133136
TI  - Are pain and function better measures of outcome than revision rates after TKR in
      the younger patient?
AB  - Revision is the gold standard outcome measurement for survival analyses of
      orthopaedic implants but reliance on revision as an endpoint has been recently
      questioned. This study, that assesses long-term outcome in a specific group of
      patients who had undergone total knee replacement (TKR) for osteoarthritis,
      highlights the main problems facing modern survival analyses. Minimum 12-year
      survival and outcome data were reviewed for a series of sixty patients under the
      age of 60 years (mean age 55.4 years) who underwent total knee replacement (TKR)
      for osteoarthritis. The patients are a subgroup from a larger consecutive series
      of 1429 patients who underwent TKR between 1987 and 1993 at a single institution.
      Whilst the main study aim was to compare outcome of TKR using different
      endpoints, the outcome of TKR in this younger subpopulation could also be
      investigated. With revision as the primary endpoint the survival for TKR was
      82.2% (95% CI 17.3). The mean OKS at follow-up (mean 15.7 years) was 30.9.
      However, many of the 82% of patients who did not undergo revision had a less than
      satisfactory outcome. 41% of these patients reported modest or severe pain (using
      the OKS) at final follow-up. A combined endpoint including revision, poor
      function and significant pain drastically reduced the survival rate for the
      operation. Survival based on revision alone provides an acceptable but inaccurate
      impression of outcome in younger TKR patients (under 60 years). A true
      representation of the success of TKR should include pain and function as
      endpoints.

PMID- 20133137
TI  - Interaction between ghrelin and the ghrelin receptor (GHS-R1a), a NMR study using
      living cells.
AB  - The study of the interaction of ghrelin (1), the endogenous ligand for the GH
      secretagogues receptor (GHS-R1a), and des-acyl ghrelin (2) with the GHS-R1a by
      NMR using living cells is presented, using GHS-R1a stably transfected cell lines
      (CHO and HEK 293) and wild type cells. Therefore, the interaction of 1 and 2 with
      the GHS-R1a receptor has been performed using quasi-physiological conditions.
      Ghrelin (1), showed a higher number of residues affected by chemical shift
      perturbation (CSP) or chemical shift exchange (CSE) effects: Ser3, Phe4, Leu5,
      Val12, Gln13/Gln14, Lys16/Lys19, Glu17 and Lys24 were much more affected in 1
      than in des-acyl ghrelin (2). The chemical shift index CSI values indicated the
      presence of a possible alpha-helical region between Glu8 and Lys20 for ghrelin
      (1). After analysing the NMR data, two possible structures have arisen, which
      present different proline rotamers: the EEZE and the EZEZ conformers, at
      positions Pro7, Pro21, Pro22 and Pro27, respectively, keeping a left-handed alpha
      helix from Glu8 to Lys20. These experimental evidences might imply that the GHS
      R1a receptor is acting as a prolyl-cis/trans isomerase.

PMID- 20133138
TI  - Antimalarial and antitubercular nostocarboline and eudistomin derivatives:
      synthesis, in vitro and in vivo biological evaluation.
AB  - The synthesis of nine nostocarboline derivatives with substitutions of the 2
      methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis
      cationic dimers linking 6-Cl-norharmane through the 2-position and fifteen
      derivatives of the marine alkaloids eudistomin N and O is reported. These
      compounds were evaluated in vitro against four parasites (Trypanosoma brucei
      rhodesiense STIB 900, Trypanosoma cruzi Tulahuen C2C4, Leishmania donovani MHOM
      ET-67/L82 axenic amastigotes, and Plasmodium falciparum K1 strain), against
      Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc(2)155 and
      Corynebacterium glutamicum ATCC13032, and cytotoxicity was determined against L6
      rat myoblast cells. Nostocarboline and derivatives displayed potent and selective
      in vitro inhibition of P. falciparum with weak cytotoxicity. The dimers displayed
      submicromolar inhibition of L. donovani and T. brucei, and nanomolar activity
      against P. falciparum, albeit with pronounced cytotoxicity. One dimer showed a
      MIC(99) value against M. tuberculosis of 2.5 microg/ml. The alkylated eudistomin
      N and O derivatives displayed activities down to 18 nM against P. falciparum for
      N-Me Eudistomin N. Four dimers, nostocarboline and three eudostomin derivatives
      were evaluated in an in vivo Plasmodium berghei mouse model. No significant
      activity was observed for the dimers, but a 50% reduction in parasitaemia was
      observed at 4 x 50 mg/kg ip for nostocarboline.

PMID- 20133139
TI  - Synthesis of novel aminoglycosides via allylic azide rearrangement for
      investigating the significance of 2'-amino group.
AB  - Using allylic azide rearrangement, a convenient method has been developed for the
      synthesis of 2',3'-dideoxyaminoglycosides that are, otherwise, difficult to be
      prepared. The antibacterial activity of these novel aminoglycosides also confirms
      the indispensable role of 2'-NH(2) group for both neomycin and kanamycin classes
      of aminoglycosides. A novel structural motif containing the hexylaminocarbonyl
      groups at O-5 and/or O-6 of 2',3'-dideoxyneamine could lead to the production of
      new aminoglycosides against resistant bacteria.

PMID- 20133140
TI  - Thermoluminescent chip detector for in vivo dosimetry in pelvis and head & neck
      cancer treatment.
AB  - Our aim is to show the TL dosimetry as a confident QA method for radiotherapy
      treatments. Before in vivo entrance dose measurements using TLD-100 chips,
      ECLIPSE TPS-simulated treatments for a Rando anthropomorphic phantom, two for
      pelvis and one head & neck. In Vivo measurements results with (60)Co beam
      remained within +/-5% limits. Results for 6 and 15 MV are in conclusion. This is
      a National Cancer Institute/RJ/Brazil study under the 13.111-IAEA Coordinated
      Research Project.

PMID- 20133141
TI  - Monte Carlo determination of water concentration effect on gamma-ray detection
      efficiency in soil samples.
AB  - Water concentration effect on full energy peak efficiency in a soil sample taken
      from a soil profile in Erzurum (39 degrees 55' N; 41 degrees 16' E; 200 m above
      sea level), Turkey was determined using Monte Carlo simulation technique. The
      dependence of the full energy peak efficiency on the water concentration in the
      soil was obtained for some particular photon energies ranging from 60 keV to 2
      MeV and, as a result, the corresponding correction factors were obtained. It was
      observed that the correction factor approaches unity with increasing energy and
      decreases with increasing water concentration.

PMID- 20133142
TI  - Activity standardization and decay data of 64Cu.
AB  - The activity of a solution of (64)Cu was measured by 4pibeta(PC)-gamma
      coincidence counting and liquid scintillation counting using the CIEMAT/NIST
      method. In addition, 4pi ionization chambers were used to establish and preserve
      calibration factors for secondary standardizations and for a determination of the
      half-life, for which a value of 12.704(5)h was measured. The photon emission
      probabilities were determined using gamma-ray spectrometry, finding values of
      p(511 keV)=0.3512(22) and p(1346 keV)=0.00474(5). The results were checked for
      consistency, and an ampoule was submitted to the BIPM to have the activity result
      entered into the database of the International Reference System (SIR), yielding
      the first entry for this radionuclide.

PMID- 20133143
TI  - Comparative study of Curiementor ionization chambers using Monte Carlo
      simulations.
AB  - Ionization chambers (ICs) are the most commonly used instrument for measuring
      activities of solutions containing radiopharmaceuticals used in nuclear medicine,
      due to their simplicity of operation and accurate measurement results. As the
      dose delivered to the patient is determined by these measurements, for optimal
      results, the activity of these radiopharmaceuticals must be determined as
      accurately as possible, so that the radioprotection requirements are accomplished
      and at the same time good therapy or imaging results are achieved. In this work,
      the response of the ionization chamber Curiementor 2, from PTW-Freiburg, was
      studied by simulation with Monte Carlo (MC) code MCNPX and compared with
      experimental results for several radionuclides. The good agreement between
      experimental and simulation results validates the used methodology. The energy
      dependent sensitivity function, S (E), was established. Several ionization
      chambers were studied for (18)F and (99m)Tc, through Monte Carlo simulation
      method. In particular, some alterations to the original design of the Curiementor
      2 were analysed, as well as the geometry of more recent chambers developed by
      PTW, namely Curiementor 3 and PET Curiementor 4. Calibration coefficients were
      compared for sources at different positions. Importance volumes were defined and
      determined for the Curiementors 2 and 3 and its ratio related with the
      corresponding ratio of sensitivity functions.

PMID- 20133144
TI  - On line high dose static position monitoring by ionization chamber detector for
      industrial gamma irradiators.
AB  - A 1 cm(3) cylindrical ionization chamber was developed to measure high doses on
      line during the sample irradiation in static position, in a (60)Co industrial
      plant. The developed ionization chamber showed to be suitable for use as a
      dosimeter on line. A good linearity of the detector was found between the dose
      and the accumulated charge, independently of the different dose rates caused by
      absorbing materials.

PMID- 20133145
TI  - Preparation of radioactive core-shell type 198Au@SiO2 nanoparticles as a
      radiotracer for industrial process applications.
AB  - Silica-coated gold nanoparticles produced by gamma-ray irradiation were bombarded
      with neutrons in a nuclear reactor in order to activate gold nuclides into Au-198
      emitting gamma radiation of 0.412-1.088 MeV. The particle size ranges from 20 to
      200 nm. The physical integrity of the particles was examined by TEM before and
      after the neutron irradiation and the silica-gold particles were not affected in
      terms of structural appearance under gamma radiation environment. The gamma
      emitting NPs can be utilized as a tracer in petrochemical and refinery industrial
      processes where the internal temperature is extremely high and the conventional
      organic radioactive labeled compound would be decomposed.

PMID- 20133147
TI  - Proceedings of the 17th International Conference on Radionuclide Metrology and
      its Applications (ICRM 2009). Preface.

PMID- 20133146
TI  - Applicability study of using in-situ gamma-ray spectrometry technique for 137Cs
      and 210Pb(ex) inventories measurement in grassland environments.
AB  - In-situ measurement of fallout radionuclides (137)Cs and (210)Pb(ex) has the
      potential to assess soil erosion and sedimentation rapidly. In this study,
      inventories of (137)Cs and (210)Pb(ex) in the soil of Inner Mongolia grassland
      were measured using an In-situ Object Counting System (ISOCS). The results from
      the field study indicate that in-situ gamma-ray spectrometry has the following
      advantages over traditional laboratory measurements: no extra time is required
      for sample collection, no reference inventories are required, more economic,
      prompt availability of the results, the ability to average radionuclide inventory
      over a large area, and high precision.

PMID- 20133148
TI  - The potential role of sunitinib in gastrointestinal cancers other than GIST.
AB  - Gastrointestinal tumors are the most frequent and lethal malignancies worldwide.
      The deeper knowledge in molecular biology mechanisms involved in carcinogenesis
      has allowed the design of new targeted drugs mainly directed against the
      epidermal growth factor receptor (EGFR), the vascular endothelial growth factor
      (VEGF) and its receptors (VEGFRs). Sunitinib is an oral multitargeted inhibitor
      of the VEGF, platelet-derived growth factor (PDGF), and c-KIT, among others,
      tyrosine kinase receptors. Therefore, sunitinib acts in a dual mode as
      antiangiogenic agent and as antitumoral drug. The aim of this review is to gather
      the preclinical rationale behind the clinical use of sunitinib in
      gastrointestinal malignancies other than gastrointestinal stromal tumors (GIST)
      and to summarize the clinical data from phase I to III trials currently
      available.

PMID- 20133149
TI  - Adjuvant endocrine therapy in postmenopausal breast cancer patients: does hormone
      receptor status influence decision-making?
AB  - Hormonal therapy, such as tamoxifen (TAM), is the cornerstone of adjuvant
      treatment for women with surgically resected early breast cancer that is hormone
      receptor-positive (HR+), typically defined by breast tumors that express the
      estrogen receptor (ER), the progesterone receptor (PgR), or both. TAM can have
      both estrogen-antagonistic and estrogen-agonistic effects, and expression of
      growth factor receptors such as human epidermal growth factor receptor (HER)2 in
      breast cancer is associated with the development of TAM resistance. Studies also
      suggest that a lack of PgR expression in tumors with positive ER status may be
      associated with increased growth factor expression, a more aggressive tumor
      phenotype, and TAM resistance. The aromatase inhibitors (AIs) anastrozole,
      letrozole, and exemestane have proven more effective than TAM as adjuvant
      hormonal therapy in postmenopausal women with HR+ disease. Some translational
      studies have also begun to investigate the efficacy of hormonal therapy according
      to PgR or HER2 status of the tumor. The AIs have proven to be an attractive
      option for patients across a broad spectrum of receptor expression profiles, and
      the potential for combination therapy using AIs and specific growth factor
      inhibitors is also under investigation.

PMID- 20133150
TI  - Mechanisms facilitating weight loss and resolution of type 2 diabetes following
      bariatric surgery.
AB  - Bariatric surgery is the most effective treatment modality for obesity, resulting
      in durable weight loss and amelioration of obesity-associated comorbidities,
      particularly type 2 diabetes mellitus (T2DM). Moreover, the metabolic benefits of
      bariatric surgery occur independently of weight loss. There is increasing
      evidence that surgically induced alterations in circulating gut hormones mediate
      these beneficial effects of bariatric surgery. Here, we summarise current
      knowledge on the effects of different bariatric procedures on circulating gut
      hormone levels. We also discuss the theories that have been put forward to
      explain the weight loss and T2DM resolution following bariatric surgery.
      Understanding the mechanisms mediating these beneficial outcomes of bariatric
      surgery could result in new non-surgical treatment strategies for obesity and
      T2DM.

PMID- 20133151
TI  - Hemovigilance in developing countries.
AB  - Hemovigilance like quality systems and audits has become an integral part of the
      Blood Transfusion Service (BTS) in the developed world and has contributed
      greatly to the development of the blood service. However developing countries are
      still grappling with donor recruitment and efforts towards sufficiency and safety
      of the blood supply. In these countries the BTS is generally fragmented and a
      national hemovigilance program would be difficult to implement. However a few
      developing countries have an effective and sustainable blood program that can
      deliver equitable, safe and sufficient blood supply to the nation. Different
      models of hemovigilance program have been introduced with variable success. There
      are deficiencies but the data collected provided important information that can
      be presented to the health authorities for effective interventions. Hemovigilance
      program modeled from developed countries require expertise and resources that are
      not available in many developing countries. Whatever resources that are available
      should be utilized to correct deficiencies that are already apparent and obvious.
      Besides there are other tools that can be used to monitor the blood program in
      the developing countries depending on the need and the resources available. More
      importantly the data collected should be accurate and are used and taken into
      consideration in formulating guidelines, standards and policies and to affect
      appropriate interventions. Any surveillance program should be introduced in a
      stepwise manner as the blood transfusion service develops.

PMID- 20133152
TI  - Preconception predictors of weight gain during pregnancy: prospective findings
      from the Central Pennsylvania Women's Health Study.
AB  - OBJECTIVES: We examined preconception (prepregnancy) predictors of pregnancy
      weight gain and weight gain that exceeds the 2009 Institute of Medicine (IOM)
      recommendations based on pre-pregnancy body mass index (BMI), in a prospective
      study. METHODS: Data are from a population-based cohort study of 1,420 women who
      were interviewed at baseline and 2 years later. The analytic sample includes 103
      women who were not pregnant at baseline and gave birth to full-term singletons
      during the follow-up period. Preconception maternal weight category as well as
      health behaviors, psychosocial stress, parity, and age were examined as
      predictors of pregnancy weight gain and of weight gain in excess of the IOM
      recommendations using multiple linear and logistic regression analysis. RESULTS:
      Pregnancy weight gain averaged 33.01 pounds, with 51% of women gaining weight in
      excess of the 2009 IOM recommendations for their preconception weight category.
      Preconception overweight (BMI = 25-29.9) increased the odds of excessive
      pregnancy weight gain nearly threefold, whereas preconception physical activity
      levels meeting activity guidelines reduced the odds of excessive weight gain but
      was marginally statistically significant. CONCLUSION: Although future research
      examining the role of physical activity in relation to pregnancy weight gain is
      needed, preconception overweight and physical activity levels are prime targets
      for interventions to avoid excessive pregnancy weight gain.

PMID- 20133154
TI  - Neuromuscular activation of vastus intermedius muscle during fatiguing exercise.
AB  - The purpose of this study was to investigate neuromuscular activation of the
      vastus intermedius (VI) muscle during fatiguing contraction. Seven healthy men
      performed sustained isometric knee extension exercise at 50% of maximal voluntary
      contraction until exhaustion. During the fatiguing task, surface electromyograms
      (EMGs) were recorded from four muscle components of the quadriceps femoris muscle
      group: VI; vastus lateralis (VL); vastus medialis (VM); and rectus femoris (RF)
      muscles. For the VI muscle, our recently developed technique was used. Root mean
      square (RMS) and median frequency (MF) of the surface EMG signal were calculated
      and these variables were then normalized by the value at the beginning of the
      task. Normalized RMS of the VI muscle resembled those of the other three muscles
      at all given times. At 95% of exhaustion time, normalized MF of the VI muscle was
      significantly higher than that of the VL muscle (p<0.05). These results suggested
      that neuromuscular activation is not consistent between the VI and VL muscles at
      the exhaustion for isometric submaximal contraction and this could reflect the
      dissimilar intramuscular metabolism between these muscles.

PMID- 20133153
TI  - How much does low socioeconomic status increase the risk of prenatal and
      postpartum depressive symptoms in first-time mothers?
AB  - OBJECTIVE: To examine socioeconomic status (SES) as a risk factor for depressive
      symptoms in late pregnancy and the early postpartum period. A secondary objective
      was to determine whether SES was a specific risk factor for elevated postpartum
      depressive symptoms beyond its contribution to prenatal depressive symptoms.
      DESIGN: Quantitative, secondary analysis, repeated measures, descriptive design.
      SETTING: Participants were recruited from paid childbirth classes serving upper
      middle class women and Medicaid-funded hospitals serving low-income clients in
      Northern California. PARTICIPANTS: A sample of 198 first-time mothers was
      assessed for depressive symptoms in their third trimester of pregnancy and at 1,
      2, and 3 months postpartum. MAIN OUTCOME MEASURE: Depressive symptoms were
      measured with the Center for Epidemiological Studies-Depression (CES-D) Scale.
      RESULTS: Low SES was associated with increased depressive symptoms in late
      pregnancy and at 2 and 3 months, but not at 1 month postpartum. Women with four
      SES risk factors (low monthly income, less than a college education, unmarried,
      unemployed) were 11 times more likely than women with no SES risk factors to have
      clinically elevated depression scores at 3 months postpartum, even after
      controlling for the level of prenatal depressive symptoms. CONCLUSION: Although
      new mothers from all SES strata are at risk for postpartum depression, SES
      factors including low education, low income, being unmarried, and being
      unemployed increased the risk of developing postpartum depressive symptoms in
      this sample.

PMID- 20133155
TI  - Percutaneous US-guided renal biopsy: a retrospective study comparing the 16-gauge
      end-cut and 14-gauge side-notch needles.
AB  - PURPOSE: Assess glomerular yield and safety profile of two different types of
      needles for percutaneous ultrasound-guided kidney biopsy. MATERIALS AND METHODS:
      Over 24 months, 121 ultrasonographic ultrasound-guided renal biopsies were
      performed on native kidneys of 121 adults: 66 with 16-gauge, 29-mm end-cut
      (BioPince) needles and 55 with 14-gauge, 1.9-mm side-notch (Tru-Cut) needles.
      RESULTS: The mean number of complete glomeruli harvested per biopsy was 21.0 and
      19.3, respectively, and the mean number of core samples required to obtain a
      satisfactory biopsy was 1.8 and 2.6, respectively. The ratio of glomeruli
      harvested to core samples needed with the end-cut needle was 58% greater than
      that with the side-notch needles (11.7 vs 7.4, respectively; difference of 4.3;
      95% confidence interval: 2.0, 6.8). Procedures performed with end-cut needles
      were associated with fewer major complications (1.5% vs 7.3% with side-notch
      needles). CONCLUSIONS: Compared to the 14-g Tru-cut needle, the 16-g end-cut
      needle provided better glomerular yield per core sample, required fewer cores for
      satisfactory tissue specimen, and resulted in fewer major complications.

PMID- 20133156
TI  - Utility of C-arm CT in patients with hepatocellular carcinoma undergoing
      transhepatic arterial chemoembolization.
AB  - PURPOSE: To evaluate the utility of C-arm computed tomography (CT) on treatment
      algorithms in patients undergoing transhepatic arterial chemoembolization for
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From March 2008 to July
      2008, 84 consecutive patients with HCC underwent 100 consecutive transhepatic
      arterial chemoembolizations with iodized oil. Unenhanced and iodinated contrast
      medium-enhanced C-arm CT with planar and three-dimensional imaging were performed
      in addition to conventional digital subtraction angiography (DSA) in all
      patients. The effect on diagnosis and treatment was determined by testing the
      hypotheses that C-arm CT, in comparison to DSA, provides (a) improved lesion
      detection, (b) expedient identification and mapping of arterial supply to a
      tumor, (c) improved characterization of a lesion to allow confident
      differentiation of HCC from pseudolesions such as arterioportal shunts, and (d)
      an improved evaluation of treatment completeness. The effect of C-arm CT was
      analyzed on the basis of information provided with C-arm CT that was not provided
      or readily apparent at DSA. RESULTS: C-arm CT was technically successful in 93 of
      the 100 procedures (93%). C-arm CT provided information not apparent or
      discernible at DSA in 30 of the 84 patients (36%) and resulted in a change in
      diagnosis, treatment planning, or treatment delivery in 24 (28%). The additional
      information included, amongst others, visualization of additional or
      angiographically occult tumors in 13 of the 84 patients (15%) and identification
      of incomplete treatment in six (7.1%). CONCLUSIONS: C-arm CT is a useful
      collaborative tool in patients undergoing transhepatic arterial chemoembolization
      and can affect patient care in more than one-fourth of patients.

PMID- 20133157
TI  - Pro and con ultrasound: are we missing the larger picture?

PMID- 20133158
TI  - Severe pulmonary artery hypertension caused by hypoglycemia after cardiac
      surgery.

PMID- 20133159
TI  - A category I indication for transesophageal echocardiography.

PMID- 20133160
TI  - Exercise training after lung transplantation: a systematic review.
AB  - BACKGROUND: Lung transplant recipients experience persistent impairments in
      exercise capacity and skeletal muscle function despite a vast improvement in lung
      function after transplantation. Exercise training may be beneficial in improving
      exercise capacity in lung transplant recipients. A systematic review was
      undertaken to examine the evidence for exercise training on functional outcomes
      in lung transplant recipients. METHODS: Studies were identified by searching
      electronic databases and scanning reference lists. Only randomized controlled
      trials, controlled trials, and prospective cohorts were included in the review.
      Seven studies met the inclusion criteria. Study quality was assessed using the
      Physiotherapy Evidence Database, Jadad, and Downs scales. RESULTS: The overall
      quality of studies was fair to moderate in assessing the effect of exercise
      training on maximal and functional exercise capacity, skeletal muscle function,
      and lumbar bone mineral density. Every study reported significant improvements in
      these outcomes. Some studies lacked randomization and/or a control group, so it
      was not possible to separate the effects of training with the natural recovery
      process after lung transplantation. CONCLUSION: Some evidence was found to
      support that a period of structured exercise training could improve maximal and
      functional exercise capacity, skeletal muscle strength, and lumbar bone mineral
      density in lung transplant recipients. Further studies are needed to determine
      the potential for exercise training to optimize these functional outcomes and to
      develop optimal guidelines for exercise prescription in the lung transplant
      population.

PMID- 20133161
TI  - A retrospective study of silicone stent placement for management of anastomotic
      airway complications in lung transplant recipients: short- and long-term
      outcomes.
AB  - BACKGROUND: Airway anastomotic complications remain a major cause of morbidity
      and mortality after lung transplantation (LT). Few data are available with regard
      to the use of silicone stents for these airway disorders. The aim of this
      retrospective study was to evaluate the clinical efficacy and safety of silicone
      stents for such an indication. METHODS: Data of adult lung transplant recipients
      who had procedures performed between January 1997 and December 2007 at our
      institution were reviewed retrospectively. We included patients with post
      transplant airway complications who required bronchoscopic intervention with a
      silicone stent. RESULTS: In 17 of 117 (14.5%) LT recipients, silicone stents were
      inserted at a mean time of 165 (range 5 to 360) days after surgery in order to
      palliate 23 anastomotic airway stenoses. Symptomatic improvement was noted in all
      patients, and mean forced expiratory volume in 1 second (FEV(1)) increased by 672
      +/- 496 ml (p < 0.001) after stent insertion. The stent-related complication rate
      was 0.13/patient per month. The latter consisted of obstructive granulomas (n =
      10), mucus plugging (n = 7) and migration (n = 7), which were of mild to moderate
      severity and were successfully managed endoscopically. Mean stent duration was
      266 days (range 24 to 1,407 days). Successful stent removal was achieved in 16 of
      23 cases (69.5%) without recurrence of stenosis. Overall survival was similar in
      patients with and without airway complications (p = 0.36). CONCLUSIONS: Silicone
      stents allow clinical and lung function improvement in patients with LT-related
      airway complications. Stent-related complications were of mild to moderate
      severity, and were appropriately managed endoscopically. Permanent resolution of
      airway stenosis was obtained in most patients, allowing definitive stent removal
      without recurrence.

PMID- 20133163
TI  - Azithromycin is associated with increased survival in lung transplant recipients
      with bronchiolitis obliterans syndrome.
AB  - BACKGROUND: Previous studies have suggested that azithromycin improves lung
      function in lung transplant recipients with bronchiolitis obliterans syndrome
      (BOS). However, these studies did not include a non-treated BOS control cohort or
      perform survival analysis. This study was undertaken to estimate the effect of
      azithromycin treatment on survival in lung transplant recipients with BOS.
      METHODS: We conducted a retrospective cohort study of consecutive lung transplant
      recipients who developed BOS between 1999 and 2007. An association between
      azithromycin treatment and death was assessed using univariate and multivariate
      time-dependent Cox regression analysis. RESULTS: Of the 178 recipients who
      developed BOS in our study, 78 did so after 2003 and were treated with
      azithromycin. The azithromycin-treated and untreated cohorts had similar baseline
      characteristics. Univariate analysis demonstrated that azithromycin treatment was
      associated with a survival advantage and this beneficial treatment effect was
      more pronounced when treatment was initiated during BOS Stage 1. Multivariate
      analysis demonstrated azithromycin treatment during BOS Stage 1 (adjusted hazard
      ratio = 0.23, p = 0.01) and absolute forced expiratory volume in 1 second
      (FEV(1)) at the time of BOS Stage 1 (adjusted hazard ratio = 0.52, p = 0.003)
      were both associated with a decreased risk of death. CONCLUSIONS: In lung
      transplant recipients with BOS Stage 1, azithromycin treatment initiated before
      BOS Stage 2 was independently associated with a significant reduction in the risk
      of death. This finding supports the need for a randomized, controlled trial to
      confirm the impact of azithromycin on survival in lung transplant recipients.

PMID- 20133164
TI  - Optimization of axial-pump pressure sensitivity for a continuous-flow total
      artificial heart.
AB  - BACKGROUND: In this study, we describe the potential advantages of a continuous
      flow total artificial heart (CFTAH) comprising two small, non-pulsatile pumps
      with optimized responsiveness to the pressure gradient. METHODS: We modified a
      MicroMed DeBakey axial-flow pump by increasing its inducer-impeller inlet angle,
      thereby increasing its pressure responsivity. We obtained the in vitro pressure
      gradient response and compared it with those of the clinically used, unmodified
      MicroMed DeBakey pump, Jarvik 2000 FlowMaker and HeartMate II. RESULTS: The
      modified pump showed an increased response to changes in the pressure gradient at
      pump flow rates of between 2 and 4 liters/min. The maximum pressure responsivity
      of the modified pump was 2.5 liters/min/mm Hg; the corresponding maximum
      responsivities of the Jarvik 2000, HeartMate II and MicroMed DeBakey ventricular
      assist devices (VADs) were 0.12, 0.09 and 0.38 liters/min/mm Hg, respectively.
      CONCLUSIONS: Because of the inherent properties of non-pulsatile pumps, the CFTAH
      may potentially respond to changes in inflow and outflow pressures while
      maintaining physiologic flow rates sufficient for normal daily activity. In
      addition, the hemodynamic interplay between the two optimized pumps should allow
      a physiologic response to normal flow imbalances between the pulmonary and
      systemic circulations. Improved responsiveness to inflow pressure may further
      simplify and improve the CFTAH and affect its potential clinical use as a
      meaningful therapy for terminal heart failure.

PMID- 20133165
TI  - Paracorporeal biventricular mechanical circulatory support for more than 4 years.
AB  - We present a patient who was evaluated for heart transplantation, but because of
      acute cardiac decompensation with cardiopulmonary resuscitation and multiorgan
      failure, had the indication for biventricular mechanical circulatory support. The
      patient was maintained on mechanical circulatory support for more than 4 years
      until he became eligible to receive a heart allograft.

PMID- 20133166
TI  - Benefit of immune monitoring in heart transplant patients using ATP production in
      activated lymphocytes.
AB  - BACKGROUND: Balancing immunosuppression to prevent rejection while minimizing
      infection or drug toxicity risk is a major challenge in heart transplantation.
      Therapeutic drug monitoring alone is inadequate to measure the immune response.
      An immune monitoring (IM) assay (ImmuKnow; Cylex, Columbia, MD) performed on
      peripheral blood measures adenosine triphosphatase (ATP) release from activated
      lymphocytes and may predict the immune state. Therefore, we sought to determine
      the utility of IM in heart transplant recipients. METHODS: Between November 2005
      and July 2008, 296 heart transplant recipients had a total of 864 IM assays
      performed at 2 weeks to 10 years post-transplant and were correlated with
      infection and rejection events that occurred within 1 month after IM testing. All
      patients received standard triple-drug immunosuppressive therapy with tacrolimus,
      mycophenolate mofetil and corticosteroids, without induction therapy. RESULTS:
      There were 38 infectious episodes and 8 rejection episodes. The average IM score
      was significantly lower during infection than steady state (187 vs 280 ng ATP/ml,
      p < 0.001). The average IM score was not significantly different during rejection
      when compared with steady state (327 vs 280 ng ATP/ml, p = 0.35). Interestingly,
      3 of 8 rejection episodes were antibody-mediated rejections and had hemodynamic
      compromise and, for these, the mean IM score was significantly higher than for
      steady-state patients (491 vs 280 ng ATP/ml, p < 0.001). CONCLUSIONS: The non
      invasive IM test appears to predict infectious risk in heart transplant patients.
      The association between high IM scores and rejection risk is inconclusive due to
      the small number of rejection episodes. Further studies with larger sample sizes
      for rejection episodes are required.

PMID- 20133167
TI  - Measuring consciousness: is one measure better than the other?
AB  - What is the best way of assessing the extent to which people are aware of a
      stimulus? Here, using a masked visual identification task, we compared three
      measures of subjective awareness: The Perceptual Awareness Scale (PAS), through
      which participants are asked to rate the clarity of their visual experience;
      confidence ratings (CR), through which participants express their confidence in
      their identification decisions, and Post-decision wagering (PDW), in which
      participants place a monetary wager on their decisions. We conducted detailed
      explorations of the relationships between awareness and identification
      performance, looking to determine (1) which scale best correlates with
      performance, and (2) whether we can detect performance in the absence of
      awareness and how the scales differ from each other in terms of revealing such
      unconscious processing. Based on these findings we discuss whether perceptual
      awareness should be considered graded or dichotomous. Results showed that PAS
      showed a much stronger performance-awareness correlation than either CR or PDW,
      particularly for low stimulus intensities. In general, all scales indicated above
      chance performance when participants claimed not to have seen anything. However,
      such above-chance performance only showed when we also observed a correlation
      between awareness and performance. Thus (1) PAS seems to be the most exhaustive
      measure of awareness, and (2) we find support for above-chance performance in the
      absence of subjective awareness, but such unconscious knowledge only contributes
      to performance when we observe conscious knowledge as well. Similarities and
      differences between scales are discussed in the light of consciousness theories
      and response strategies.

PMID- 20133168
TI  - Animal models of abdominal aortic aneurysm and their role in furthering
      management of human disease.
AB  - Abdominal aortic aneurysm is a common degenerative disorder associated with
      sudden death due to aortic rupture. Current therapy is limited to open surgical
      repair of the aorta or endovascular placement of covered stents to exclude the
      abdominal aortic aneurysm from the circulation. A number of different animal
      models have been developed in order to study abdominal aortic aneurysm in an
      effort to advance current management deficiencies. Large animal models have been
      mostly used to assist in developing novel methods to surgically treat abdominal
      aortic aneurysms. Small animal models, particularly those developed in rodents,
      have been employed to further the understanding of the mechanisms involved in
      abdominal aortic aneurysm in order to identify potential new medical treatments.
      It is expected that findings from these animal models will contribute importantly
      to new treatments for human abdominal aortic aneurysm. This review explores the
      animal models which are used in abdominal aortic aneurysm research and highlights
      their advantages and disadvantages.

PMID- 20133169
TI  - Aortic aneurysms in systemic lupus erythematosus: a meta-analysis of 35 cases in
      the literature and two different pathogeneses.
AB  - BACKGROUND: Aortic aneurysms including dissection are uncommon complications of
      systemic lupus erythematosus, but the incidence has been increasing with an
      improved prognosis for this disease. However, the mechanisms contributing to
      aneurysm formation in systemic lupus erythematosus have not been fully clarified.
      METHODS: A meta-analysis of published cases was conducted to clarify the patient
      characteristics that may contribute to aneurysm formation in systemic lupus
      erythematosus. A search of relevant studies published over the past 40 years
      (1969-2008) was carried out in the publications on aortic aneurysms with systemic
      lupus erythematosus, and 35 cases were identified. The contributing factors to
      aneurysm formation as well as the patient prognosis were searched for sex, age,
      duration of corticosteroid treatment, aneurysm site (thoracic and/or abdominal),
      mortality, evidence of atherosclerotic involvement, and presence or absence of an
      operation, rupture, dissection, cystic medial degeneration, vasculitis, and
      hypertension. Each of these factors was assigned to each point score. Based on
      the point scores, a statistical analysis of rank correlation was thereafter
      performed. RESULTS: The factors correlating with the presence of thoracic or
      abdominal lesions differed significantly. The presence of thoracic aneurysms
      correlated with dissection and cystic medial degeneration, whereas abdominal
      lesions correlated with the finding of atherosclerosis. Thoracic lesions showed a
      high rate of death, while abdominal lesions were associated with a relatively
      favorable prognosis. Abdominal lesions were related to the duration of steroid
      therapy. The other correlations among the various factors were also evaluated,
      with the finding of cystic medial degeneration associated with vasculitis.
      CONCLUSION: Two principal patterns emerged from this analysis. One was the fatal
      nonatherosclerotic thoracic aneurysm which was associated with cystic medial
      degeneration and probably due to vasculitis. The other was atherosclerotic
      abdominal aneurysm which was complicated by long-term steroid treatment and it
      showed a relatively favorable prognosis.

PMID- 20133170
TI  - The Society for Cardiovascular Pathology celebrating 25 disruptively exciting
      years.
AB  - It was 25 years ago when the Society for Cardiovascular Pathology was first
      organized. The Society has since devoted itself to the advancement of
      understanding about heart and blood vessel disorders, especially their diagnosis,
      and for the improvement of prevention, management, and treatment. In this 25 year
      span, the Society has accomplished many goals and met its initial commitments as
      an organization, dedication to education and learning, and to collegiality. With
      the many exciting steps the Society has taken in the first 25 years, it is sure
      to move to new and significantly transformative endeavours in the coming decades.

PMID- 20133171
TI  - A forgotten population: addressing comprehensive HIV prevention needs among
      American Asians and Pacific islanders.

PMID- 20133172
TI  - Difference in psychosocial well-being between paternal and maternal AIDS orphans
      in rural China.
AB  - This study compares psychosocial well-being between paternal and maternal orphans
      in rural China in a sample (n = 459) of children who had lost one parent to HIV
      and who were in family-based care. Measures included academic marks, education
      expectation, trusting relationships with current caregivers, self-reported health
      status, depression, loneliness, posttraumatic stress, and social support. No
      significant differences were reported between maternal and paternal orphans,
      except that paternal orphans reported better trusting relationships with
      caregivers than maternal orphans. Children with a healthy surviving parent
      reported significantly better scores for depression, loneliness, posttraumatic
      stress, and social support than children with a sick parent. Analyses showed
      significance with regard to orphan status on academic marks and trusting
      relationships with caregivers while controlling for age, gender, surviving
      parent's health status, and family socioeconomic status. Results underscore the
      importance of psychosocial support for children whose surviving parent is living
      with HIV or another illness.

PMID- 20133173
TI  - Levetiracetam in the treatment of neonatal seizures: a pilot study.
AB  - PURPOSE: At present, neonatal seizures are usually treated with Phenobarbital
      (PB) despite the limited efficacy and the potential risk this treatment holds for
      the developing brain. We report here a prospective pilot feasibility study on the
      use of Levetiracetam as monotherapy in the treatment of neonatal seizures.
      METHODS: Six newborns (body weight>2000 g, gestational age>30 weeks) presenting
      with neonatal seizures were enrolled. Patients whose seizures were caused by
      electrolyte disturbances or hypoglycemia, or whose seizures did respond to
      pyridoxine were excluded. Patients previously treated with other antiepileptic
      drugs (AEDs), with the exception of single PB doses before and during titration,
      were excluded. LEV was administered orally, increasing the dose by 10mg/(kg day)
      over 3 days. Endpoint was the need of any additional AEDs (or PB) after day 3, or
      3 months of LEV treatment. A decision regarding further treatment was made on an
      individual basis and follow-up was documented up to 8 months of age. RESULTS: No
      severe adverse effects were observed. Mild sedation was reported in one infant.
      All six patients treated with oral LEV became seizure free within 6 days. Five
      patients remained seizure free after 3 months with ongoing LEV monotherapy. One
      infant developed pharmacoresistant epilepsy. Seizures relapsed later in the
      clinical course of two more patients, one of whom was no longer under LEV
      therapy. DISCUSSION: Results from our small patient group indicate that LEV may
      be an alternative therapeutic option in neonatal seizures.

PMID- 20133174
TI  - Evaluation of a novel haematology analyser for use with feline blood.
AB  - A novel haematology analyser was evaluated for its use with feline samples.
      Complete blood cell counts, a five-part differential count, and reticulocyte
      numbers were determined, and the results compared with reference data.
      Coefficients of correlation, Passing-Bablok regression analysis and Bland-Altmann
      difference plots with biases and 95% limits of agreement are reported. Precision
      and linearity were also studied. The instrument demonstrated very low
      imprecision, and the tested range of linearity exceeded the reference ranges
      provided by the manufacturer. For all parameters except monocytes (r = 0.65), the
      analyser results correlated well with reference methods. Compared with the manual
      count of aggregated reticulocytes, the instrument showed good agreement with a
      positive bias. The optical platelet count correlated well with the manual chamber
      count. In conclusion the analyser was found to be highly reliable for the
      analysis of feline blood samples in a large veterinary laboratory.

PMID- 20133175
TI  - Reduction of patient dose in medical radiography by utilizing scattered X-rays:
      relation between permissible limit of scatter fraction, viewer brightness, and
      perceptibility of vision.
AB  - This paper proposes a new technique for reducing the patient dose when employing
      medical radiographs prepared by using screen-film systems. In this technique the
      patient dose can be reduced by employing scattered X-rays in order to obtain the
      same film density as that realized without the use of scattered X-rays. The
      minimum perceptible thickness difference DeltaX(min), which can be recognized by
      liminal vision, was psychophysically calculated by considering the energy
      spectrum of incident X-ray, sensitivity spectrum of the screen layer, and the
      perception capability of human vision. From the calculated DeltaX(mins) in
      various conditions, the permissible upper limit of scatter fraction for obtaining
      the same DeltaX(min) for three kinds of luminances, and the fraction of reduction
      in the primary X-rays were determined. As an example of the results, when the
      object size required for perception is 1.3 mm, a scatter fraction up to 42% can
      be permitted at a density D of 1.0 for a luminance of 2548 cd m(-2). When we
      increase the luminance of the viewer from 478 cd m(-2) to 2548 cd m(-2), the
      upper limit of the permitted scatter fraction varies from 30% to 42% at a D of
      1.0, i.e., the patient dose can be reduced by 17% under the same perceptibility
      of DeltaX(min) by utilizing scattered X-rays. This reduction can be successfully
      achieved by changing the lead content of the grid from 0.45 to 0.38 g cm(-2).

PMID- 20133176
TI  - [Wounds with different aetiology treated using larval debridement therapy:
      presentation of two cases].
AB  - This paper describes two cases of wounds with different aetiology and dissimilar
      size which were treated with Larval Debridement Therapy. Two different techniques
      of Larval Debridement were used for each case: Free Range and BioFoam larvae.
      Observations and treatment were carried out in a Primary Health Centre in
      Barcelona, Spain. The application and observations were performed by two nurses
      with the collaboration of two family physicians. The Larval Therapy efficacy
      outcome was checked with an Ulcer Reverse Stage Scale (PUSH v2), by taking
      photographs and a Visual Analogue Pain Scale (VAPS) was completed by both
      subjects before and after the treatment. It was observed in both cases that the
      larval therapy caused debridement of all fibrin and collagen tissue, and the
      slough dropped to a normal level. As a consequence of this change the PUSH scale
      punctuations were improved. On the negative side, the therapy was associated with
      an increase in pain. The beneficial effect of applying Larval Therapy enables
      following a basic wound healing care plan. The larval debridement therapy did not
      pose any threat for the patients; they could go about their Activities of the
      Daily Life (ADL) without any change. These wound cases treated with larval
      debridement therapy are the first ones reported in the Primary Health Care field
      in Spain.

PMID- 20133177
TI  - Effect of melt-processing and ultrasonic treatment on physical properties of high
      amylose maize starch.
AB  - High-amylose maize starch (Hylon VII) was submitted to melt-processing in an
      internal mixer at 100 degrees C and 40 rpm for 8 min. Glycerol was used as a
      plasticiser at different polymer/glycerol ratios. Torque and temperature curves
      were obtained. After glycerol extraction with ethyl alcohol, the samples were
      dispersed at 5 g/L, and treated by ultrasound radiation at the same conditions
      for 30 min. Samples were characterised by (1)H NMR spectrometry, viscosity
      measurements, and X-ray diffractometry. The results revealed that both glycerol
      and water had an important role on the crystallinity properties of the resulting
      products. Melt-processed and sonicated samples showed similar (1)H NMR spectra.
      Ultrasound treatment caused a significant reduction in intrinsic viscosity for
      the sample previously processed with the highest glycerol content, probably
      because of its higher solubility in water.

PMID- 20133178
TI  - Abiotic stresses and induced BVOCs.
AB  - Plants produce a wide spectrum of biogenic volatile organic compounds (BVOCs) in
      various tissues above and below ground to communicate with other plants and
      organisms. However, BVOCs also have various functions in biotic and abiotic
      stresses. For example abiotic stresses enhance BVOCs emission rates and patterns,
      altering the communication with other organisms and the photochemical cycles.
      Recent new insights on biosynthesis and eco-physiological control of constitutive
      or induced BVOCs have led to formulation of hypotheses on their functions which
      are presented in this review. Specifically, oxidative and thermal stresses are
      relieved in the presence of volatile terpenes. Terpenes, C6 compounds, and methyl
      salicylate are thought to promote direct and indirect defence by modulating the
      signalling that biochemically activate defence pathways.

PMID- 20133179
TI  - Evolution and phyletic distribution of two-component signal transduction systems.
AB  - Two-component signal transduction systems are abundant in prokaryotes. They
      enable cells to adjust multiple cellular functions in response to changing
      environmental conditions. These systems are also found, although in much smaller
      numbers, in lower eukaryotes and plants, where they appear to control a few very
      specific functions. Two-component systems have evolved in Bacteria from much
      simpler one-component systems bringing about the benefit of extracellular versus
      intracellular sensing. We review reports establishing the origins of two
      component systems and documenting their occurrence in major lineages of Life.

PMID- 20133180
TI  - Auxiliary phosphatases in two-component signal transduction.
AB  - Signal termination in two-component systems occurs by loss of the phosphoryl
      group from the response regulator protein. This review explores our current
      understanding of the structures, catalytic mechanisms and means of regulation of
      the known families of phosphatases that catalyze response regulator
      dephosphorylation. The CheZ and CheC/CheX/FliY families, despite different
      overall structures, employ identical catalytic strategies using an amide side
      chain to orient a water molecule for in-line attack of the aspartyl phosphate.
      Spo0E phosphatases contain sequence and structural features that suggest a
      strategy similar to the chemotaxis phosphatases but the mechanism used by the Rap
      phosphatases is not yet elucidated. Identification of features shared by
      phosphatase families may aid in the identification of currently unrecognized
      classes of response regulator phosphatases.

PMID- 20133182
TI  - FTIR and FTRaman spectra, assignments, ab initio HF and DFT analysis of 4
      nitrotoluene.
AB  - In this work, the experimental and theoretical study on molecular structure and
      vibrational spectra of 4-nitrotoluene are studied. The FTIR and FTRaman
      experimental spectra of the molecule have been recorded in the range of 4000-100
      cm(-1). Making use of the recorded data, the complete vibrational assignments are
      made and analysis of the observed fundamental bands of molecule is carried out.
      The experimental determinations of vibrational frequencies are compared with
      those obtained theoretically from ab initio HF and DFT quantum mechanical
      calculations using HF/6-31G (d, p), B3LYP/6-31++G* (d, p) and B3LYP/6-311++G* (d,
      p) methods. The differences between the observed and scaled wave number values of
      most of the fundamentals are very small in B3LYP than HF. The geometries and
      normal modes of vibrations obtained from ab initio HF and B3LYP calculations are
      in good agreement with the experimentally observed data. Comparison of the
      simulated spectra provides important information about the ability of the
      computational method (B3LYP) to describe the vibrational modes. The vibrations of
      NO(2) and CH(3) groups coupled with skeletal vibrations are also investigated.

PMID- 20133181
TI  - Interaction fidelity in two-component signaling.
AB  - Two component signal transduction systems and phosphorelays have been adapted and
      amplified by bacteria to respond to a multitude of environmental, metabolic and
      cell cycle signals while maintaining essentially identical structures for the
      domains responsible for recognition and phosphotransfer between the sensor
      histidine kinase and the response regulator. Co-crystal structures of these
      domains have revealed the variable residues at the interaction surface of the two
      components responsible for interaction specificity in signal transfer. This
      information has formed the basis for the development and validation of
      statistical methods to identify interaction residues and surfaces from compiled
      databases of interacting proteins and holds forth the promise of determining
      structures of multi-protein complexes and signaling networks.

PMID- 20133183
TI  - Novel Fe (III) heterochelates: synthesis, structural features and fluorescence
      studies.
AB  - Fluorescence properties of five 4-acyl pyrazolone based hydrazides (H(2)SB(n))
      and their Fe (III) heterochelates of the type [Fe(SB(n))(L)(H(2)O)].mH(2)O
      [H(2)SB(n)=nicotinic acid [1-(3-methyl-5-oxo-1-phenyl-4,5-di hydro-1H-pyrazol
      4yl)-acylidene]-hydrazide; where acyl=-CH(3), m=4 (H(2)SB(1)); -C(6)H(5), m=2
      (H(2)SB(2)); -CH(2)-CH(3), m=3 (H(2)SB(3)); -CH(2)-CH(2)-CH(3), m=1.5
      (H(2)SB(4)); -CH(2)-C(6)H(5), m=1.5 (H(2)SB(5)) and HL=1-cyclopropyl-6-fluoro-4
      oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid] were studied at
      room temperature. The fluorescence spectra of heterochelates show red shift,
      which may be due to the chelation by the ligands to the metal ion. It enhances
      ligand ability to accept electrons and decreases the electron transition energy.
      The kinetic parameters such as order of reaction (n), energy of activation
      (E(a)), entropy (S*), pre-exponential factor (A), enthalpy (H*) and Gibbs free
      energy (G*) have been reported.

PMID- 20133184
TI  - Adsorption of isoniazid onto sepiolite-palygorskite group of clays: An IR study.
AB  - The adsorption of isoniazid (INH) on sepiolite, loughlinite (natural Na
      sepiolite) and palygorskite from Anatolia was investigated by FT-IR spectroscopy.
      Experimental results indicated that INH molecules, adsorbed on sepiolite
      palygorskite group of clays, are coordinated to surface hydroxyls by H-bonding
      interaction through the pyridine ring nitrogen lone pairs. Moreover, some of the
      adsorbed INH molecules may enter the interior channels of the sepiolite
      palygorskite structure and involve H-bonding interaction with zeolitic water.
      Some intensity and frequency changes in the OH stretching band of surface
      hydroxyls (Si-OH) of the INH-treated sepiolite and loughlinite were observed.
      However, this band is found to be less affected by the adsorption of isoniazid in
      the case of palygorskite, probably because the surface Si-OH groups in
      palygorskite appear to be less abundant than in sepiolite or loughlinite.

PMID- 20133185
TI  - Phylogenetic analysis of human P[8]G9 rotavirus strains circulating in Brazil
      reveals the presence of a novel genetic variant.
AB  - BACKGROUND: Group A rotavirus (RV-A) genotype P[8]G9 has emerged as one of the
      leading causes of gastroenteritis in children worldwide and currently is
      recognized as one of the five most common genotypes detected in humans. High
      intragenotype diversity in G9 RV-A has been observed, and nowadays, based on the
      genetic variability of the VP7 gene, six different phylogenetic lineages and
      eleven sublineages were described. OBJECTIVES: To study the degree of genetic
      variation and evolution of Brazilian P[8]G9 RV-A strains. STUDY DESIGN:
      Phylogenetic analysis of 19 P[8]G9 RV-A strains isolated from 2004 to 2007 in
      five different Brazilian states was conducted using the NSP1, NSP3, NSP5, VP4 and
      VP7 genes. For the VP4 and VP7 genes, 3D protein structure predictions were
      generated to analyze the spatial distribution of amino acid substitutions
      observed in Brazilian strains. RESULTS: Based on the phylogenetic analyses, all
      Brazilian strains clustered within lineage G9-III and P[8]-3 for VP7 and VP4,
      respectively, and were classified as genotype A1, T1 and H1 for the NSP1, NSP3
      and NSP5 genes, respectively. Interestingly, all the strains isolated in Acre
      State (Northern Brazil) formed a closely related cluster clearly separated from
      the other Brazilian and prototype strains with regard to the five genes studied.
      Unique amino acid substitutions were observed in Acre strains in comparison with
      the prototype and Brazilian strains. CONCLUSION: Inclusion of Acre strains in the
      phylogenetic analysis revealed the presence of a novel genetic variant and
      demonstrated a diversification of P[8]G9 rotaviruses in Brazil.

PMID- 20133186
TI  - Relative lymphopenia and monocytosis may be considered as a surrogate marker of
      pandemic influenza a (H1N1).

PMID- 20133187
TI  - Relationship between insomnia and pain in major depressive disorder: A sleep
      diary and actigraphy study.
AB  - OBJECTIVES: Insomnia and pain are frequent complaints during the course of a
      major depressive episode. We analyzed the association between insomnia and pain
      symptoms using subjective and objective sleep measures. METHODS: This is a
      prospective, naturalistic follow-up study in a university-based psychiatric unit.
      Ninety-one Chinese patients were enrolled during an acute episode of major
      depressive disorder (mean age=48years, 73 women); 82 of them were reassessed
      3months later using the same assessment on sleep, pain, depressive, and anxiety
      symptoms. Clinician-rated insomnia symptoms were obtained using the insomnia
      items of the Hamilton Rating Scale for Depression. Subjective sleep disturbances
      were assessed using the Insomnia Severity Index (ISI). Detailed sleep pattern was
      acquired using sleep diary and actigraphy. Pain intensity was evaluated using a
      verbal rating scale, a visual analog scale, and a multidimensional pain scale.
      RESULTS: Cross-sectional analyses found that insomnia symptoms and quantitative
      sleep parameters were related to pain symptoms. The correlations between sleep
      and pain scores were more significant after 3months of pharmacotherapy as
      compared to baseline. After controlling for the severity of anxiety and
      depression, the ISI total score and actigraphy-derived wake after sleep onset and
      total sleep time remained significant in predicting pain. CONCLUSION: This study
      supports specific role of subjective sleep disturbances and actigraphic measures
      in predicting pain symptoms in major depressive disorder. Further studies using a
      micro-longitudinal design are necessary to find out the causal relationship
      between sleep and pain in depressed patients.

PMID- 20133188
TI  - The efficacy of cognitive-behavioral therapy for insomnia in patients with
      chronic pain.
AB  - STUDY OBJECTIVES: To assess the efficacy of cognitive-behavioral therapy for
      insomnia (CBT-I) in patients with non-malignant chronic pain. METHODS: Twenty
      eight subjects with chronic neck and back pain were stratified according to
      gender, age, and ethnicity, then assigned to one of the two treatment groups: CBT
      I or a contact control condition. INTERVENTION: Eight weeks of CBT-I including
      sleep restriction, stimulus control, sleep hygiene, and one session of cognitive
      therapy devoted to catastrophic thoughts about the consequences of insomnia.
      MEASUREMENTS AND RESULTS: Outcomes included sleep diary assessments of sleep
      continuity, pre-post measures of insomnia severity (ISI), pain (Multidimensional
      Pain Inventory), and mood (BDI and POMS). Subjects receiving CBT-I (n=19), as
      compared to control subjects (n=9), exhibited significant decreases in sleep
      latency, wake after sleep onset, number of awakenings, and significant increase
      in sleep efficiency. The diary findings were paralleled by significant changes in
      the ISI (p=0.05). Significant improvement (p=0.03) was found on the Interference
      Scale of the Multidimensional Pain Inventory. The groups did not significantly
      differ on mood measures or measures of pain severity. CONCLUSIONS: CBT-I was
      successfully applied to patients experiencing chronic pain. Significant
      improvements were found in sleep as well as in the extent to which pain
      interfered with daily functioning. The observed effect sizes for the sleep
      outcomes appear comparable to or better than meta-analytic norms for subjects
      with Primary Insomnia.

PMID- 20133189
TI  - Initial use of portable monitoring versus polysomnography to confirm obstructive
      sleep apnea in symptomatic patients: an economic decision model.
AB  - BACKGROUND: When using portable (level III and level IV) studies to "rule in"
      obstructive sleep apnea (OSA) in symptomatic patients, the pre-test probability
      (P) needs to be sufficiently high to minimize patients with negative tests who
      require full polysomnography. METHODS: We used a theoretical decision analysis
      model to assess the pre-test probability above which it would be appropriate to
      use portable studies to rule in disease in symptomatic patients with suspected
      OSA. For the base case, we considered a symptomatically sleepy patient referred
      with a probability of OSA of P. We determined the lower threshold of P
      appropriate for a clinical algorithm based upon an initial ambulatory study
      compared to initial diagnosis with PSG by comparing costs using the PSG algorithm
      with a diagnostic algorithm involving initial assessment with a portable study.
      RESULTS: In our base case, the pre-test probability above which portable testing
      would be less costly than initial diagnostic PSG would be 0.47. When an initial
      split night study was compared to portable testing, the pre-test probability
      above which portable testing was more economically attractive was greater (0.68).
      Values of P, however, varied considerably depending on values of many variables,
      including costs of diagnostic testing and CPAP compliance. CONCLUSIONS: Using a
      decision model, we have developed a theoretical framework to ascertain the pre
      test disease probability above which portable studies would be economically
      attractive as an initial test in the assessment of patients with suspected OSA.

PMID- 20133190
TI  - Sleep apnea in Parkinson's disease: when is it significant?

PMID- 20133191
TI  - Rapid occurrence of depression following addition of sodium oxybate to modafinil.

PMID- 20133192
TI  - Fatal familial insomnia: a middle-age-onset Chinese family kindred.

PMID- 20133193
TI  - Association between sleep patterns and daytime functioning in children with
      insomnia: the contribution of parent-reported frequency of night waking and wake
      time after sleep onset.
AB  - OBJECTIVE: The aim of this study was to investigate the association between sleep
      patterns and daytime functioning in children with insomnia. Furthermore, the role
      of frequency of night waking and wake time after sleep onset for daytime
      functioning was analyzed in the context of total sleep time and sleep onset
      latency. METHODS: Families with children with parent-perceived sleep problems
      were recruited for diagnostic clarification and subsequent treatment (if
      indicated) at an outpatient clinic. Out of 49 families seeking help, 34 children
      (age 5.2-10.9 years, mean 7.1 years) and their parents were included in the
      present study. Sleep and sleep problems were assessed by a structured clinical
      interview according to the diagnostic criteria of the International
      Classification of Sleep Disorders (ICSD-II). Parents kept a sleep diary over two
      weeks. In addition, they answered the Child Behavior Checklist, questions
      concerning the daytime sleepiness of their children, as well as a structured
      clinical interview assessing comorbid mental disorders. RESULTS: Reduced parent
      reported total sleep time predicted more delinquent behavior and more
      concentration problems. Independent of total sleep time and frequency of night
      waking, longer parent-reported wake time after sleep onset was associated with
      greater daytime sleepiness, which in turn predicted more social problems.
      CONCLUSIONS: Besides total sleep time, wake time after sleep onset could be
      another important determinant for specific aspects of daytime functioning in
      children with insomnia.

PMID- 20133194
TI  - Insomnia cycling with a 42-day infradian period: evidence for two uncoupled
      circadian oscillators?
AB  - OBJECTIVE: To describe the unique case of a middle-aged woman with severe
      insomnia recurring with a regular infradian period without any other significant
      clinical condition. To infer the existence of a circadian dysfunction modeled
      according to the physical phenomenon of the "beats." PATIENT/METHODS: A two-year
      prospective observation by means of a sleep log was performed during the
      patient's normal life. She underwent one month of motor activity recording and
      also polysomnography, circadian rhythm of body core temperature and psychiatric
      evaluation during periods with and without insomnia. RESULTS: Visual inspection
      of the 293-day plot of the sleep log disclosed a regular 42-day rhythm of
      insomnia recurrence confirmed by a Discrete Fourier Transform. During the periods
      of insomnia, lasting 5-7days, only moderate mood symptoms (depressive overlapping
      hypomaniac symptoms) were present. Treatment with sodium valproate was effective
      in curtailing insomnia. CONCLUSION: The wax and wane infradian modulation of the
      sleep length suggested the presence of a basic mechanism similar to the physical
      phenomenon of the "beats," i.e., a long period modulation of the amplitude of an
      oscillating system due to the interference of two uncoupled oscillators with a
      slightly different oscillation frequency. Hypothesizing a dysfunction of the
      circadian component of sleep, namely two uncoupled circadian cycles, a simple
      mathematical model estimated the difference of their periods of oscillation |34+/
      2min| and reproduced the sleep-log data of the drug-free period of observation.

PMID- 20133195
TI  - Insomnia: how tricky can it get?

PMID- 20133196
TI  - A proteomic investigation of Streptococcus agalactiae grown under conditions
      associated with neonatal exposure reveals the upregulation of the putative
      virulence factor C protein beta antigen.
AB  - Streptococcus agalactiae is a major neonatal pathogen that is able to adapt to a
      variety of host environments, including both rectal and vaginal maternal
      carriage, growth in amniotic fluid and at various neonatal body sites. As such it
      is important to elucidate the patterns of protein expression that are associated
      with S. agalactiae growth under these different in vivo conditions. To this end,
      we have grown S. agalactiae strain A909 under in vitro conditions reflecting
      those associated with maternal vaginal carriage (low pH, low oxygen, nutrient
      stress) and those associated with exposure to body fluids during invasive disease
      (neutral pH, aeration, nutrient sufficient). The protein profiles of bacterial
      cells grown under each of these conditions were compared using a proteome
      approach. A total of 76 proteins were reproducibly identified 16 of which were
      shown to be differentially expressed. The putative virulence factor C protein
      beta and several proteins linked to resistance to oxidative stress were found to
      be upregulated under the conditions hypothesised to reflect those associated with
      foetal exposure to S. agalactiae. Thus, these data add to the currently limited
      understanding of the molecular basis of S. agalactiae GBS adaptation to different
      environmental conditions.

PMID- 20133197
TI  - Association of polymorphisms in proinflammatory cytokine genes with the
      development of oral cancer in Southern Thailand.
AB  - Oral squamous cell carcinoma (OSCC) is highly prevalent in southeastern Asia
      suggesting that region-specific environmental and biological factors contribute
      to the development of this cancer. Exposure to oral carcinogens (i.e. betel quid)
      and pathogenic agents (i.e. papilloma virus) is common among individuals that
      develop OSCC in countries such as Thailand, India etc. However, not all
      individuals with such exposures develop the disease suggesting that other factors
      further increase susceptibility to OSCC. It is therefore plausible that
      functional variants in DNA repair genes and/or genes controlling inflammation and
      immunological response play a role in determining susceptibility to OSCC.
      Previous studies (including ours) have found an association between variants in
      DNA repair genes and increased susceptibility to OSCC. By extension, the current
      study examined the association between SNPs in genes encoding proteins involved
      in inflammation and immunomodulation (IL1alpha, IL1beta, IL8, TNFalpha) and OSCC.
      A total of 107 cases and 157 controls were analyzed. OSCC cases were more likely
      to carry the "T" allele at the IL1alpha(+4845) SNP than controls (OR=2.0, 1.0
      4.4). OSCC cases that smoke and drink were more likely to carry either the "T"
      allele at the IL1beta(+3953) SNP (OR=10.4, 1.1-93.2) or the "C" allele at the
      TNFalpha(-1031) SNP (OR=3.4, 1.0-11.4) than controls. These results support the
      hypothesis that variants in inflammatory or immunomodulatory genes influence
      susceptibility to OSCC in Thailand. Larger studies are needed to confirm these
      results and more importantly to properly investigate the complex interactions
      among genetic variants in DNA repair and inflammation and other non-genetic
      susceptibility factors. In addition, laboratory experiments designed to determine
      the functional properties of the genetic variants are needed.

PMID- 20133198
TI  - Targeting the hypnozoite reservoir of Plasmodium vivax: the hidden obstacle to
      malaria elimination.
AB  - Plasmodium vivax is the major species of malaria parasite outside Africa. It is
      especially problematic in that the infection can relapse in the absence of
      mosquitoes by activation of dormant hypnozoites in the liver. Medicines that
      target the erythrocytic stages of Plasmodium falciparum are also active against
      P. vivax, except where these have been compromised by resistance. However, the
      only clinical therapy against relapse of vivax malaria is the 8-aminoquinoline,
      primaquine. This molecule has the drawback of causing haemolysis in genetically
      sensitive patients and requires 14 days of treatment. New, safer and more-easily
      administered drugs are urgently needed, and this is a crucial gap in the broader
      malaria-elimination agenda. New developments in cell biology are starting to open
      ways to the next generation of drugs against hypnozoites. This search is urgent,
      given the time needed to develop a new medication.

PMID- 20133199
TI  - Altered first-trimester screening markers after IVF/ICSI: no relationship with
      small-for-gestational-age and number of embryos transferred.
AB  - First-trimester serum markers in 110 in-vitro fertilization (IVF) and 331
      intracytoplasmatic sperm injection (ICSI) pregnancies were compared with 1431
      pregnancies with spontaneous conception. Alterations of serum markers were
      evaluated with respect to small-for-gestational-age (SGA) growth and number of
      embryos transferred. For pregnancy-associated plasma protein A (PAPP-A),
      significantly lower concentrations were observed in IVF and ICSI pregnancies
      compared with controls (0.86 and 0.9 versus 1.06; P<0.001). Free beta-human
      chorionic gonadotrophin (betaHCG) values were significantly higher in the
      IVF/ICSI groups than in controls (1.1 and 1.1 versus 0.94; P<0.005). IVF and ICSI
      pregnancies showed higher rates of SGA (10.0% and 8.2%) compared with natural
      conception (4.6%), but differences in PAPP-A concentrations remained significant
      (P<0.005) after the exclusion of SGA pregnancies. No relationship between serum
      values and the transfer of one, two or three embryos was observed. Centre
      specific corrections may be needed to adjust screening parameters for assisted
      reproductive technology.

PMID- 20133200
TI  - LH concentrations do not correlate with pregnancy in rFSH/GnRH antagonist cycles.
AB  - The possible relationship between endogenous LH concentrations and clinical
      outcome was evaluated in 750 patients treated with a standardized gonadotrophin
      releasing hormone (GnRH) antagonist and recombinant FSH (rFSH)-only protocol.
      Serum LH concentrations were measured during stimulation by a central laboratory
      and patients were stratified into quantiles of <P25, P25-P75, and >P75. The P25
      values were 3.38 IU/l, 0.93 IU/l, and 0.91 IU/l on stimulation days 1, 5, and 8,
      respectively. The ongoing pregnancy rates per started cycle of patients within
      the <P25 subset on stimulation day 1, 5, or 8 were highly similar to those in the
      P25-P75, and >P75 subsets and ranged in the various subsets between 35.0% and
      39.5%. In keeping with previous, smaller studies, these findings demonstrate that
      in good prognosis, non-obese patients endogenous LH in a GnRH antagonist protocol
      is able to support treatment with rFSH only.

PMID- 20133202
TI  - Transfusion and Apheresis Science. Editorial.

PMID- 20133201
TI  - Complete globozoospermia associated with PLCzeta deficiency treated with calcium
      ionophore and ICSI results in pregnancy.
AB  - Globozoospermia is an infrequent pathology in which spermatozoa lack acrosomes.
      Patients are considered sterile without IVF augmented with intracytoplasmic sperm
      injection (ICSI), as fertilization is impaired due to absence of oocyte
      activation. As far as is known, this is the first study to report results of a
      comprehensive approach to the treatment of the semen parameters, sperm DNA
      fragmentation, aneuploidy, transmission electron microscopy, Western blotting and
      immunofluorescence for detection of phospholipase C zeta (PLCzeta), as well as
      ICSI outcome, of an affected patient. Morphological evaluation and transmission
      electron microscopy revealed complete globozoospermia with significant duplicate
      heads and tails. Analysis for DNA damage revealed fragmentation rates of
      approximately 80% in semen and 15-23% in swim-up fractions. PLCzeta was not
      detected by immunofluorescence or Western blotting. Aneuploidy rates were within
      normal ranges. ICSI followed by oocyte activation with calcium ionophore resulted
      in high rates of fertilization, and an ongoing pregnancy was established after
      transfer of cryopreserved-thawed embryos.

PMID- 20133203
TI  - A new trick for an old dog: pulsed dexamethasone treatment for chronic
      inflammatory demyelinating polyneuropathy.

PMID- 20133204
TI  - Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic
      inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double
      blind, randomised, controlled trial.
AB  - BACKGROUND: Pulsed high-dose dexamethasone induced long-lasting remission in
      patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in
      a pilot study. The PREDICT study aimed to compare remission rates in patients
      with CIDP treated with high-dose dexamethasone with rates in patients treated
      with standard oral prednisolone. METHODS: In eight neuromuscular centres in the
      Netherlands and one in the UK, patients aged 18 years or older who had newly
      diagnosed definite or probable CIDP were randomly assigned to a treatment regimen
      of either pulsed high-dose dexamethasone or standard oral prednisolone.
      Randomisation was done with a random number generator. The primary outcome
      measure was remission at 12 months, defined as improvement of at least three
      points on the Rivermead mobility index and improvement of at least one point on
      the inflammatory neuropathy cause and treatment disability scale. Analysis was by
      intention to treat. This trial is registered with Current Controlled Trials,
      number ISRCTN07779236. FINDINGS: Between December, 2003, and December, 2008, 40
      patients were treated: 24 received dexamethasone and 16 received prednisolone. At
      12 months, 16 patients were in remission: ten in the dexamethasone group and six
      in the prednisolone group (odds ratio [OR] 1.2, 95% CI 0.3-4.4). Most adverse
      events were minor and did not differ substantially between treatment groups;
      however, sleeplessness and Cushing's face occurred more often in the prednisolone
      group. INTERPRETATION: Pulsed high-dose dexamethasone treatment did not induce
      remission more often than prednisolone treatment. A substantial proportion of
      patients were in remission at 12 months in both treatment groups. High-dose
      dexamethasone could be considered as induction therapy in CIDP, but comparison
      with intravenous immunoglobulin treatment is needed. FUNDING: The Prinses Beatrix
      Fonds (MAR01-0213) and the Department of Neurology, Academic Medical Center.

PMID- 20133205
TI  - Psychometric properties of the Norwegian MacNew Heart Disease health-related
      quality of life inventory.
AB  - BACKGROUND: MacNew is a health-related quality of life (HQOL) inventory for
      patients with ischaemic heart disease and includes three domains; emotional,
      physical and social. The MacNew gives new opportunities to compare directly
      patients with the three major ischaemic heart diagnoses, angina, myocardial
      infarction and heart failure. However, this inventory has not earlier been
      evaluated in Norwegian. OBJECTIVE: The purpose of this study was to validate the
      Norwegian version of the disease-specific HQOL inventory MacNew by assessing the
      measurement model, internal consistent reliability and test-retest and convergent
      validity. METHOD: Patients with ischaemic heart disease (n=124; angina pectoris,
      n=53; myocardial infarction, n=35; and heart failure; n=36) participated in this
      cross-sectional study. Patients completed the self-administered MacNew and the
      generic HQOL-instrument SF-36. The MacNew and the SF-36 were repeated 2-3 weeks
      later (test-retest) by 17 patients. RESULTS: The psychometric properties were
      satisfactory to good. The construct validity assessed by factor analysis
      explained 61.5% of the variance. The internal consistent reliability was high
      (exceeded 0.90 in all domains). The test-retest analysis showed equivalent
      results demonstrating good reproducible properties. The convergent validity
      within each domain was evaluated with correlation analysis, demonstrating
      correlations of 0.74, 0.69 and 0.71 on the emotional, physical and social
      domains, respectively. CONCLUSION: The Norwegian version of the MacNew inventory
      demonstrated satisfactory to good psychometric properties and can be recommended
      for evaluating HQOL for patients with heart diseases in clinical studies.

PMID- 20133206
TI  - Potentiation of TLR9 responses for human naive B-cell growth through RP105
      signaling.
AB  - Toll-like receptor 9 (TLR9) signals induce important pathways in the early
      defense against microbial pathogens. Although TLR9 signaling can activate memory
      B cells directly, efficient naive B cell responses seem to require additional,
      but as yet unidentified, signals. We explored the effects of RP105 (CD180) on CpG
      DNA-activated naive and memory B cells from normal controls and patients with
      common variable immunodeficiency (CVID). RP105 dramatically enhanced CpG DNA
      induced proliferation/survival by naive B cells but not by memory B cells. This
      enhancement was mediated by TLR9 upregulation induced by RP105, leading to Akt
      activation and sustained NF-kappaB activation. CpG DNA-activated CVID B cells
      showed enhancement of proliferation/survival by RP105 and produced specific IgM
      antibody to Streptococcus pneumoniae polysaccharides in response to interleukin
      21 stimulation. Thus, RP105 strongly affects expansion of the naive B-cell pool,
      and suggests that the putative RP105 ligand (s) upon cytokine stimulation
      facilitates antibody-mediated acute pathogen clearance.

PMID- 20133207
TI  - Preface. Human Reproduction.

PMID- 20133208
TI  - The sleep-wake cycle in adult rats following pilocarpine-induced temporal lobe
      epilepsy.
AB  - The relationship between sleep and epilepsy is both complex and clinically
      significant. Temporal lobe epilepsy (TLE) influences sleep architecture, while
      sleep plays an important role in facilitating and/or inhibiting possible
      epileptic seizures. The pilocarpine experimental model reproduces several
      features of human temporal lobe epilepsy and is one of the most widely used
      models in basic research. The aim of the present study was to characterize,
      behaviorally and electrophysiologically, the phases of sleep-wake cycles (SWC) in
      male rats with pilocarpine-induced epilepsy. Epileptic rats presented spikes in
      all phases of the SWC as well as atypical cortical synchronization during
      attentive wakefulness and paradoxical sleep. The architecture of the sleep-wake
      phases was altered in epileptic rats, as was the integrity of the SWC. Because
      our findings reproduce many relevant features observed in patients with epilepsy,
      this model is suitable to study sleep dysfunction in epilepsy.

PMID- 20133209
TI  - P wave and the development of atrial fibrillation.
AB  - BACKGROUND: Terminal P-wave inversion in lead V(1) representing left atrial
      overload has been considered a precursor of atrial fibrillation (AF). OBJECTIVE:
      The purpose of this study was to determine whether this P-wave morphologic
      characteristic can predict the development of AF. METHODS: Digital analysis of 12
      lead ECGs was performed to enroll patients with P terminal force > or =0.06 s x 2
      mm in lead V(1) from among a database of 308,391 ECG recordings. The prognostic
      value of ECG characteristics for developing AF was determined. RESULTS: A total
      of 78 patients (mean age 52 +/- 19 years) with left atrial overload were chosen
      from among 102,065 patients in the database. During mean follow-up of 43 months,
      15 (19%) patients developed AF (AF group) versus 63 (81%) patients who did not
      (non-AF group). No significant difference was noted between the AF and non-AF
      groups with regard to the area, duration, and amplitude of the P-wave terminal
      portion in lead V(1). In contrast, the area, duration, and amplitude of the P
      wave initial portion in the same lead were significantly greater in the AF group
      than in the non-AF group (114.6 +/- 73.0 microV x ms vs 73.1 +/- 59.3 microV x
      ms, 42.2 +/- 12.4 ms vs 35.7 +/- 10.1 ms, and 94.0 +/- 39.9 microV vs 68.8 +/-
      49.4 microV, respectively; P <.05 for each). Multivariate analysis confirmed that
      the area of the P-wave initial portion was independently associated with the
      development of AF (hazard ratio 4.02, 95% confidence interval 1.25-17.8; P =
      .018). CONCLUSION: P-wave initial portion in lead V(1) was an independent risk
      stratifier of AF development in patients with marked left atrial overload.

PMID- 20133210
TI  - RAD51D protects against MLH1-dependent cytotoxic responses to O(6)-methylguanine.
AB  - S(N)1-type methylating agents generate O(6)-methyl guanine (O(6)-meG), which is a
      potently mutagenic, toxic, and recombinogenic DNA adduct. Recognition of O(6)
      meG:T mismatches by mismatch repair (MMR) causes sister chromatid exchanges,
      which are representative of homologous recombination (HR) events. Although the
      MMR-dependent mutagenicity and toxicity caused by O(6)-meG has been studied, the
      mechanisms of recombination induced by O(6)-meG are poorly understood. To explore
      the HR and MMR genetic interactions in mammals, we used the Rad51d and Mlh1 mouse
      models. Ablation of Mlh1 did not appreciably influence the developmental
      phenotypes conferred by the absence of Rad51d. Mouse embryonic fibroblasts (MEFs)
      deficient in Rad51d can only proliferate in p53-deficient background. Therefore,
      Rad51d(-/-)Mlh1(-/-)Trp53(-/-) MEFs with a combined deficiency of HR and MMR were
      generated and comparisons between MLH1 and RAD51D status were made. To our
      knowledge, these MEFs are the first mammalian model system for combined HR and
      MMR defects. Rad51d-deficient MEFs were 5.3-fold sensitive to N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) compared to the Rad51d-proficient MEFs. A pronounced G2/M
      arrest in Rad51d-deficient cells was accompanied by an accumulation of gamma-H2AX
      and apoptosis. Mlh1-deficient MEFs were resistant to MNNG and showed no G2/M
      arrest or apoptosis at the doses used. Importantly, loss of Mlh1 alleviated
      sensitivity of Rad51d-deficient cells to MNNG, in addition to reducing gamma
      H2AX, G2/M arrest and apoptosis. Collectively, the data support the hypothesis
      that MMR-dependent sensitization of HR-deficient cells is specific for O(6)-meG
      and suggest that HR resolves DNA intermediates created by MMR recognition of O(6)
      meG:T. This study provides insight into recombinogenic mechanisms of
      carcinogenesis and chemotherapy resulting from O(6)-meG adducts.

PMID- 20133211
TI  - What is the best method for measuring renal function in adults and children with
      cystic fibrosis?
AB  - AIMS: To measure the glomerular filtration rate (GFR) in adults and children with
      cystic fibrosis (CF) using a radio-isotope technique as the gold standard and to
      compare this to serum creatinine based equations, serum cystatin C levels and
      tobramycin clearance, and to determine which method correlates most closely with
      measured GFR in this population.

PMID- 20133212
TI  - Simultaneous quantification of venlafaxine and O-desmethylvenlafaxine in human
      plasma by ultra performance liquid chromatography-tandem mass spectrometry and
      its application in a pharmacokinetic study.
AB  - A rapid, selective and sensitive ultra performance liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS) method was developed to simultaneously determine
      venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) in human plasma. Sample
      pretreatment involved a one-step extraction with diethyl ether of 0.5 mL plasma.
      The separation was carried out on an ACQUITY UPLC BEH C(18) column with 10 mmol/L
      ammonium acetate and methanol as the mobile phase at a flow rate of 0.30 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 linear calibration curves for VEN and ODV were both obtained in the
      concentration range of 0.200-200 ng/mL (r(2)> or =0.99) with the lower limit of
      quantification (LLOQ) of 0.200 ng/mL. The intra- and inter-day precision
      (relative standard deviation, R.S.D.) values were less than 13% and the accuracy
      (relative error, R.E.) was within +/-5.3% and +/-3.6% for VEN and ODV. The method
      herein described was superior to previous methods in sensitivity and sample
      throughput and successfully applied to clinical pharmacokinetic study of
      venlafaxine sustained-release capsule in healthy male volunteers after oral
      administration.

PMID- 20133213
TI  - Simultaneous determination of paracetamol, pseudoephedrine, dextrophan and
      chlorpheniramine in human plasma by liquid chromatography-tandem mass
      spectrometry.
AB  - For the first time, a highly sensitive and simple LC-MS/MS method after one-step
      precipitation was developed and validated for the simultaneous determination of
      paracetamol (PA), pseudoephedrine (PE), dextrophan (DT) and chlorpheniramine (CP)
      in human plasma using diphenhydramine as internal standard (IS). The analytes and
      IS were separated on a YMC-ODS-AQ C(18) Column (100 mm x 2.0 mm, 3 microm) by a
      gradient program with mobile phase consisting of 0.3% (v/v) acetic acid and
      methanol at a flow rate of 0.30 mL/min. Detection was performed on a triple
      quadrupole tandem mass spectrometer via electrospray ionization in the positive
      ion mode. The method was validated and linear over the concentration range of 10
      5000 ng/mL for PA, 2-1000 ng/mL for PE, 0.05-25 ng/mL for DT and 0.1-50 ng/mL for
      CP. The accuracies as determined from quality control samples were in range of 
      8.37% to 3.13% for all analytes. Intra-day and inter-day precision for all
      analytes were less than 11.54% and 14.35%, respectively. This validated method
      was successfully applied to a randomized, two-period cross-over bioequivalence
      study in 20 healthy Chinese volunteers receiving multicomponent formulations
      containing 325 mg of paracetamol, 30 mg of pseudoephedrine hydrochloride, 15 mg
      of dextromethorphan hydrobromide and 2 mg of chlorphenamine maleate.

PMID- 20133214
TI  - [Recommendations for the management of influenza in pediatrics (2009-2010).]
AB  - Specific action plans from various institutions, governments and scientific
      societies have been identified and implemented to combat the A H1N1 2009
      influenza virus pandemic. This document sets out the recommendations of the
      Spanish Association of Pediatrics for the management of influenza in children for
      influenza season 2009-2010. The risk factors for influenza A H1N1 2009 in
      pediatric patients, the clinical course, severity and complications are similar
      to seasonal influenza. In most cases, the diagnosis of influenza will be based on
      clinical suspicion, without viral subtype differentiation. In a patient with
      influenza virus infection, the criteria for referral and hospital admission will
      be based broadly on the signs of clinical severity or complications, regardless
      of the causative virus. Children with influenza but with no signs of clinical
      severity or complications do not require antiviral treatment. Physical measures
      of hygiene and isolation are essential to reduce the transmissibility of the
      disease. The influenza vaccines in infancy, for both seasonal influenza and for
      influenza A H1N1 2009, should be directed primarily at patients with risk
      factors.

PMID- 20133215
TI  - Contribution of lip proportions to facial aesthetics in different ethnicities: a
      three-dimensional analysis.
AB  - BACKGROUND: Lip augmentations are commonly performed procedures in the United
      States, with annual numbers surpassing 100 000. While lips contribute to facial
      beauty, the relative influence of this feature to whole facial appeal has not yet
      been established. What is also of increasing interest is the consideration of
      ethnic differences in the evaluation of beauty. However, most current
      anthropometric measurements refer to Caucasians, and their use in the treatment
      of Asian American patients would be inappropriate. METHODS: Three-dimensional
      models of 197 male and female Caucasian, Chinese and Korean subjects were created
      using surface-imaging technology. The lips and corresponding faces from these
      models were ranked according to subjective aesthetic appeal by 20 male and female
      raters of various ages, occupations and ethnicities. The raters' results were
      subsequently compared with individually measured lip parameters. RESULTS:
      Rankings between lips and their corresponding whole faces differed greatly. Lips
      that were rated as the most attractive were smaller than average in midline upper
      lip surface heights, bilateral paramedian lip surface heights, upper lip angles
      and volume in the lower lip. Both Asian groups exhibited significantly different
      lip parameters and lip-projection volumes from that of Caucasians. CONCLUSIONS:
      The results from this study suggest that there are indeed measurable differences
      in the baseline Asian lip morphology as compared with Caucasians. Tailoring lip
      enhancement treatment to each individual's anatomy, ethnic background and
      personal goals can optimise outcomes. What is also of interest is that lips did
      not contribute as much to facial attractiveness as previously thought.

PMID- 20133216
TI  - Low dose of Hyaluronidase to treat over correction by HA filler--a case report.

PMID- 20133217
TI  - Necrolytic migratory erythema with cholangiocarcinoma: Pseudoglucagonoma
      syndrome.

PMID- 20133218
TI  - Disseminated Penicillium Marneffei infection with verrucoid lesions in an AIDS
      patient in Beijing, a non-endemic region.
AB  - Penicillium marneffei (PM) infection is prevalent in South-East Asia and Southern
      China and has been considered an acquired immunodeficiency syndrome (AIDS)
      defining disease. This report focused on the verrucoid proliferative lesions of
      P. marneffei infection in a 34-year-old Chinese female AIDS patient from a non
      endemic region. She recovered after receiving intravenous amphotericin B followed
      by oral itraconazole therapy. At the same time, highly active antiretroviral
      therapy (HAART) was also started. She responded very well to the treatment.

PMID- 20133219
TI  - Chronic mucocutaneous candidiasis, from bench to bedside.
AB  - Chronic mucocutaneous candidiasis (CMC) defines a heterogeneous group of orphan
      and inherited syndromes characterised by chronic and recurrent infections of the
      skin and mucosa with the yeast Candida. Increasing evidence suggests that this
      inefficient defence against Candida species is reflected by a DC/T cell defect
      which results in an impaired Th17 and Th1 immune response and, consecutively, a
      failed immune instruction of tissue cells. Little is known about the incidence
      and prognosis of CMC. Clinically, the main complications are debilitating hands
      (Candida granuloma) and oesophageal stricture with potential mal-digestion/
      absorption. Furthermore, the chronic infections are likely a risk factor for the
      development of squamous cell carcinoma. Since resistance to anti-mycotic drugs
      evolves rapidly, efficient and flexible therapeutic management is essential for
      CMC patients.

PMID- 20133220
TI  - An unusual presentation of xeroderma pigmentosum in a Caucasian child.

PMID- 20133221
TI  - A novel COL1A1 exon 14/PDGFB fusion gene in dermatofibrosarcoma protuberans.

PMID- 20133222
TI  - Simplifying living donor liver transplantation.
AB  - BACKGROUND: Living donor liver transplantation is a complex surgical operation.
      Treatment policies and operative techniques evolved in the last two decades. DATA
      SOURCES: Our center's experience in living donor liver transplantation was
      reviewed in conjunction with relevant publications in the literature. RESULTS:
      The surgical techniques and perioperative surgical therapeutics could be modified
      towards simplicity. Examples include regular inclusion of the middle hepatic vein
      without compromising the venous outflow of the donor's remnant left liver. This
      provides excellent venous outflow, which is crucial for a small-for-size graft.
      Immunosuppression and hepatitis B suppression are steroid free and hepatitis B
      immunoglobulin free respectively. CONCLUSION: The most practical way to achieve
      high graft and recipient survival rates with an acceptably low donor risk is
      through design of a protocol that simplifies the surgery and postoperative
      management.

PMID- 20133223
TI  - Clinical management of hepatitis B virus infection correlated with liver
      transplantation.
AB  - BACKGROUND: As a radical cure for post-hepatitis B virus (HBV)-related liver
      cirrhosis and hepatocellular carcinoma, liver transplantation has been applied in
      many medical centers. Before the use of effective measures, hepatitis B
      recurrence and the existence of HBsAg(+) donors, patients with hepatitis B
      related diseases are contraindicated for liver transplantation. Application of
      interferon, hepatitis B immunoglobulin (HBIG), and nucleotide analogues (e.g.,
      lamivudine) has made great progress in the clinical care of HBV. However, there
      are still many shortcomings such as low viral suppression rate, rising expense,
      and the induction of HBV tyrosine-methionine-aspartate-aspartate (YMDD) mutation.
      This article systematically reviews the current evidence that immunotherapy,
      conventional drug combinations, and some special fields of HBV infection
      correlate with liver transplantation. DATA SOURCES: Studies were identified by
      searching MEDLINE and PubMed for articles using the keywords "hepatitis B virus",
      "hepatitis B vaccination", "lamivudine", "adefovir", "entecavir", "tenofovir",
      "HBV genotype", and "liver transplantation" up to October 2009. Additional papers
      were identified by a manual search of the references from the key articles.
      RESULTS: Hepatitis B vaccine and human monoclonal antibody have very good
      clinical prospects. Compared with traditional therapies, the new medical regimens
      have many benefits such as boosting viral suppression rate and decreasing medical
      expenses. The triple therapy for YMDD mutation also has an excellent therapeutic
      effect and a low barrier to resistance. New nucleos(t)ide analogues (entecavir
      and tenofovir) eliminate virus more effectively with few adverse reactions, and
      may replace lamivudine or HBIG in future. CONCLUSIONS: Hepatitis B vaccine needs
      further large-scale and rigorous randomized controlled trials to confirm its
      effective dose and injection frequency. Monoclonal antibody is still
      experimental, and the next step is to carry out the relevant animal and human
      studies. A consensus standard regimen for the treatment of hepatitis B should be
      developed.

PMID- 20133224
TI  - Potential etiopathogenesis of seventh day syndrome following living donor liver
      transplantation: ischemia of the graft?
AB  - BACKGROUND: Seventh-day syndrome (7DS) is an early serious complication following
      liver transplantation with a high mortality because of its unknown
      etiopathogenesis. This study aimed to analyze the potential etiopathogenesis of
      7DS. METHODS: A retrospective analysis of 98 consecutive living donor liver
      transplants performed from 2001 to 2007 at our center revealed that 5 patients
      had suffered from 7DS; their age, MELD score, portal vein inflow and other
      parameters were compared with those of the other recipients. RESULTS: The 5
      patients showed common features: (a) initial uneventful recovery, and a dramatic
      rise of serum liver enzyme levels 1 to 2 weeks later; (b) decreased inflow in the
      portal vein accompanied by augmentation of serum creatinine and urea nitrogen
      level; and (c) serial liver biopsy findings of apoptosis and ischemic necrosis of
      hepatocytes. Four of the 5 patients died. Age, waiting time to transplantation,
      MELD score, operation time, cold ischemic time, portal interceptive time and
      diameter of the portal vein were not significantly different between the 2
      groups, but a difference was found in the flow rate of the portal vein (t=3.234,
      P<0.001). CONCLUSIONS: The 5 patients suffered from a decreased portal vein
      inflow, ischemic liver necrosis, and renal failure. Hence, hypoperfusion of the
      liver graft was considered to be the etiopathogenesis of 7DS, for which, however
      sufficient evidence is lacking. More studies of 7DS are needed.

PMID- 20133225
TI  - Critical flicker frequency for diagnosis and assessment of recovery from minimal
      hepatic encephalopathy in patients with cirrhosis.
AB  - BACKGROUND: Minimal hepatic encephalopathy (MHE) impairs quality of life and
      predicts overt hepatic encephalopathy (HE) in cirrhotic patients. Diagnosis of
      MHE requires cumbersome tests. Lactulose is effective in the treatment of MHE.
      This study aimed to evaluate the use of critical flicker frequency (CFF) for the
      diagnosis of MHE in cirrhotic patients after treatment. METHODS: One hundred and
      ten patients were evaluated by psychometry (number connection tests A, B or
      figure connection tests A, B), P300 auditory event related potential (P300ERP),
      venous ammonia, and CFF for MHE. MHE was diagnosed by abnormal psychometry (>2SD
      age matched controls) and P300ERP. MHE patients were treated with lactulose for
      one month. Response was defined by normalization (<2SD of matched controls) of
      both psychometry and P300ERP. RESULTS: Of the 110 patients [Child Turcott Pugh
      score A:B:C 39:42:29 (age 41.6+/-11.6 years, M:F 82:28)], 75 (68%) had abnormal
      results of psychometric tests, and 74 (67%) had prolonged P300ERP. Fifteen (20%)
      patients with abnormal results of psychometric tests had normal P300ERP. Thus
      sixty (54.5%) patients were diagnosed as having MHE. After treatment for one
      month, 34 (57%) recovered while 26 (43%) continued to have abnormal resents of
      psychometric or P300ERP tests. CFF was <39 Hz in 72 (65.4%) patients before
      treatment and in 20 (33.3%) after treatment. CFF sensitivity, specificity,
      positive predictive value, negative predictive value, and diagnostic accuracy for
      the assessment of recovery of MHE were 65%, 91%, 85%, 77% and 80%, respectively.
      CONCLUSION: CFF is a simple, relatively reliable, and accurate test without any
      dependence on age or literacy in the diagnosis and assessment of recovery of
      patients with MHE.

PMID- 20133226
TI  - Risk factors for early recurrence of small hepatocellular carcinoma after
      curative resection.
AB  - BACKGROUND: Poorer prognosis is seen in patients with hepatocellular carcinoma
      (HCC) after curative hepatic resection with early recurrence (<or=1 year) than in
      those with late recurrence (>1 year). This study aimed to identify risk factors
      for postoperative early recurrence of small HCC (<or=3 cm in diameter). METHODS:
      The study population consisted of 158 patients who underwent curative resection
      for small HCC between January 2002 and July 2004. Risk factors for early
      recurrence were analyzed. RESULTS: Thirty-three (20.8%) patients developed early
      recurrence after surgery. Univariate analysis showed the following significant
      risk factors for early recurrence in small HCC: serum alpha-fetoprotein (AFP)
      level >100 ng/ml, lack of tumor capsule formation, microscopic vascular invasion,
      high Edmonson-Steiner grades, and cytokeratin-19 (CK-19) expression (P<0.05).
      Multivariate stepwise logistic regression analysis showed that serum AFP level
      >100 ng/ml (odds ratio 2.561, 95% confidence interval 1.057 to 6.206, P=0.037)
      and microscopic vascular invasion (odds ratio 4.549, 95% confidence interval
      1.865 to 11.097, P=0.001) were independent factors. CONCLUSIONS: Postoperative
      early recurrence is related to serum AFP level >100 ng/ml and microscopic
      vascular invasion in patients with small HCC. Adjuvant therapy and careful follow
      up are required for patients with these risk factors.

PMID- 20133227
TI  - Comparatively lower postoperative hepatolithiasis risk with
      hepaticocholedochostomy versus hepaticojejunostomy.
AB  - BACKGROUND: Optimal surgical technique plays a key role in preventing the
      postoperative recurrence of hepatolithiasis. Tian et al developed the
      subcutaneous tunnel and hepatocholangioplasty using the gallbladder (STHG)
      technique and applied it in hepatolithiasis patients who had an approximately
      normal gallbladder and sphincter of Oddi. However, the technique is
      controversial. In the present study, a canine model was established for
      hepatocholangioplasty (HC) and hepaticojejunostomy (HJ) to simulate STHG and Roux
      en-Y cholangiojejunostomy in the clinic, respectively. Then, the alterations of
      bile components in the vicinity of the anastomosis were compared. This may
      provide an experimental guide for choosing an optimal technique for the treatment
      of hepatolithiasis in the clinic. METHODS: The animals were randomly separated
      into a control group (5 dogs) and a model group (stenosis of the common bile
      duct; 24 dogs). The 24 dogs in the model group were randomly divided into an HC
      group and an HJ group (12/group). Bile was collected from the bile duct at 1 and
      5 months after the operation, and the bile components were determined. RESULTS:
      The levels of total bile acid, cholesterol, total bilirubin, and phospholipid in
      the HC group were higher than those in the HJ group (P<0.05). However, no
      statistical difference was seen in unconjugated bilirubin and calcium ions. The
      mucin level in bile in the HC group was lower than that in the HJ group at 5
      months after the operation (P<0.05). The postoperative lipid peroxidation level
      was remarkably lower than that in the HJ group (P<0.05). However, the superoxide
      dismutase level was remarkably higher than that in the HJ group (P<0.05).
      Finally, a significant difference was found in the positive bacterial culture
      rate in bile between the groups. CONCLUSION: Changes of bile components near the
      anastomosis after HC might be more preferable for preventing hepatolithiasis
      formation than HJ.

PMID- 20133228
TI  - Primary hepatic neuroendocrine carcinoma: clinical analysis of 11 cases.
AB  - BACKGROUND: Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare,
      and fewer than 300 cases have been reported in the English/Chinese-language
      literature, therefore it is difficult to make a proper diagnosis and determine a
      therapeutic approach. METHODS: Eleven PHNEC patients were admitted to our
      hospital between January 1996 and May 2008. Laboratory examination, digestive
      endoscopy, B-ultrasonography, CT, MRI, or PET-CT were performed on the patients
      for preoperative diagnosis. All patients received liver resection. Some patients
      received transcatheter arterial chemoembolization (TACE), percutaneous ethanol
      injection treatment (PEIT), or octreotide injection when a recurrence was found.
      The patients' clinical data were recorded and all patients were followed up.
      RESULTS: The patients were confirmed pathologically as having PHNEC . Their
      median follow-up time was 33 months (12-107 months). All patients survived, and
      the longest post-operative survival time was 107 months, the longest disease-free
      survival time was 98 months, the 1-year survival rate was 100%, and the 1-year
      recurrence rate was 45.5% (5/11). CONCLUSIONS: Since PHNEC is easy to confuse
      with hepatocellular carcinoma, careful screening of symptoms is needed to avoid
      misdiagnosis. Resection is the first choice of treatment for PHNEC and provides
      the most favorable outcomes including long-term survival. Other treatment such as
      TACE and PEIT can be considered as well, especially when a tumor recurs.

PMID- 20133229
TI  - Effect of sodium salicylate on oxidative stress and insulin resistance induced by
      free fatty acids.
AB  - BACKGROUND: It has been reported that high-dose salicylates improve free fatty
      acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but
      the mechanism remains uncertain. In insulin-resistant rats, we found that the
      supplementation of sodium salicylate is associated with a reduction of plasma
      malondialdehyde (MDA), a marker of oxidative stress. Few studies have
      investigated the effects of salicylates on oxidative stress levels in insulin
      resistant animal models. This study aimed to assess the effect of sodium
      salicylate on insulin sensitivity and to explore the potential mechanism by which
      it improves hepatic and peripheral insulin resistance. METHODS:
      Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate
      (IHS) were separately infused for 7 hours in normal Wistar rats. During the last
      2 hours of the infusion, hyperinsulinemic-euglycemic clamping was performed with
      [6-3H] glucose tracer. Plasma glucose was measured using the glucose oxygenase
      method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA
      levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal
      muscle were measured with colorimetric kits. RESULTS: Compared with infusion of
      SAL, IH infusion increased hepatic glucose production (HGP), and decreased
      glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids
      increased the MDA levels and decreased the GSH-PX activity in the liver and
      muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05),
      reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35%
      (P<0.05). CONCLUSIONS: Short-term elevation of fatty acids induces insulin
      resistance by enhancing oxidative stress levels in the liver and muscle. The
      administration of the anti-inflammatory drug sodium salicylate reduces the degree
      of oxidative stress, therefore improving hepatic and peripheral insulin
      resistance. IKK-beta and NF-kappaB provide potential pathogenic links to
      oxidative stress.

PMID- 20133230
TI  - Endoscopic nasojejunal feeding tube placement in patients with severe
      hepatopancreatobiliary diseases: a retrospective study of 184 patients.
AB  - BACKGROUND: Total parenteral nutrition (TPN) has been recognized as the mainstay
      of nutritional support in patients with severe hepatopancreatobiliary (HPB)
      diseases for decades. However, recent studies advocate the utilization of
      endoscopic nasojejunal feeding tube placement (ENFTP), rather than the
      conventional approach. This study was designed to compare the clinical value of
      ENFTP and TPN in patients with severe HPB diseases. METHODS: Two groups of
      patients with severe HPB diseases were analyzed retrospectively. One group of 88
      patients received ENFTP, and the other 96 received TPN. Routine blood levels,
      serum glucose and prealbumin, hepatic and renal function, serum lipid, and
      calcium were measured at baseline and after 1, 2, and 4 weeks of nutritional
      support. Also, complication rate, mortality, nutritional support time, mechanical
      ventilation time, mean length of time in intensive care unit, and duration of
      hospital stay were analyzed. RESULTS: After 4 weeks of nutritional support, the
      degree of recovery of red blood cells, prealbumin, and blood glucose was greater
      in the ENFTP than in the TPN group (P<0.05). Furthermore, the ENFTP group showed
      a lower incidence of septicemia, multiple organ dysfunction syndrome, peri
      pancreatic infection, biliary infection, and nosocomial infection, in addition to
      shorter nutritional support time and hospital stay (P<0.05). CONCLUSIONS: ENFTP
      is much more effective than TPN in assisting patients with severe HPB diseases to
      recover from anemia, low prealbumin level, and high serum glucose, as well as in
      decreasing the rates of various infections (pulmonary infection excluded),
      multiple organ dysfunction syndrome rate, nutrition support time, and length of
      hospital stay. Therefore, ENFTP is safer and more economical for clinical
      application.

PMID- 20133231
TI  - Outpatient versus inpatient laparoscopic cholecystectomy: a single center
      clinical analysis.
AB  - BACKGROUND: Outpatient laparoscopic cholecystectomy (OPLC) developed in the
      United States and other developed countries as one of the fast-track surgeries
      performed in ambulatory centers. However, this practice has not been installed as
      a routine practice in the major general hospitals and medical centers in China.
      We designed this case-control study to evaluate the feasibility, benefits, and
      safety of OPLC. METHODS: Two hundred patients who had received laparoscopic
      cholecystectomy for various benign gallbladder pathologies from April 2007 to
      December 2008 at Jinling Hospital of Nanjing University School of Medicine were
      classified into two groups: OPLC group (100 patients), and control group (100),
      who were designated for inpatient laparoscopic cholecystectomy (IPLC). Data were
      collected for age, gender, indications for surgery, American Society of
      Anesthesiology (ASA) class, operative time, blood loss during surgery, length of
      hospitalization, and intra- and post-operative complications. The expenses of
      surgery and in-hospital care were calculated and analyzed. The operative
      procedures and instrumentation were standardized for laparoscopic
      cholecystectomy, and the procedures were performed by two attending surgeons
      specialized in laparoscopic surgery. OPLC was selected according to the standard
      criteria developed by surgeons in our hospital after review. Reasons for
      conversion from laparoscopic to open cholecystectomy were recorded and
      documented. RESULTS: One hundred patients underwent IPLC following the selection
      criteria for the procedure, and 99% completed the procedure. The median operative
      time for IPLC was 24.0 minutes, blood loss was 16.2 ml, and the time for resuming
      liquid then soft diet was 10.7 hours and 22.0 hours, respectively. Only one
      patient had postoperative urinary infection. The mean hospital stay for IPLC was
      58.2 hours, and the cost for surgery and hospitalization was 8770.5 RMB yuan on
      average. Follow-up showed that 90% of the patients were satisfied with the
      procedure. In the OPLC group, 99% of the patients underwent the procedure with a
      median operative time of 21.6 minutes and bleeding of 14.7 ml. The patients took
      liquid 11.3 hours then soft diet 20.1 hours after surgery. The mean postoperative
      hospital stay was 28.5 hours. In this group, 89% of the patients were discharged
      within the first 24 hours, and the remaining 11% were released within 48 hours
      after surgery. Two patients developed local complications. The cost for surgery
      and hospitalization was 7235.7 RMB yuan, which was 17.5% less than that in the
      IPLC group. At follow-up, 94% of the patients were satisfied with the surgery and
      short hospital stay. CONCLUSIONS: OPLC can effectively treat a variety of benign,
      non-acute gallbladder diseases with shortened waiting time and postoperative
      hospital stay. OPLC benefits the hospital with a rapid bed turnover rate, and
      reduces cost for surgery and hospitalization.

PMID- 20133232
TI  - Is bactibilia a predictor of poor outcome of pancreaticoduodenectomy?
AB  - BACKGROUND: Although bile infection has been proposed to increase infective
      complications following pancreaticoduodenectomy, its association with infective
      complications and non-infective complications like pancreatic fistula is still
      controversial. METHODS: Seventy-six patients who had undergone
      pancreaticoduodenectomy between July 2007 and December 2008 were included in a
      prospective database and their data analyzed. In all patients intraoperative bile
      from the bile duct was cultured. Preoperative, intra-operative, and post
      operative variables were recorded and analyzed. RESULTS: Bile culture showed
      positive growth in 35 patients and negative growth in 41. Twenty patients in the
      positive group underwent ERCP and stenting. The patients with a positive bile
      culture had a higher incidence of infective complications including intra
      abdominal abscess (n=8), wound infection (n=27), bacteremia (n=10), and renal
      insufficiency (n=9). There was no increase in the rate of non-infective
      complications of pancreaticoduodenectomy including pancreatic fistula (n=7),
      delayed gastric emptying (n=9), and post-operative hemorrhage (n=3). The hospital
      stay was significantly prolonged in the patients with a positive bile culture
      (P=0.0002). CONCLUSIONS: Pre-operative biliary drainage is significantly
      associated with bile infection, and bile infection increases the overall rates of
      infective complications and renal insufficiency. Because of the high incidence of
      complications is associated with infected bile, routine intra-operative bile
      culture is recommended in patients undergoing pancreaticoduodenectomy. Pre
      operative prophylaxis is dependent on sensitivity of cases to perioperative
      antibiotics and intra-operative bile culture report. Because of its significant
      association with infected bile, biliary stenting should be used in strictly
      selected cases.

PMID- 20133233
TI  - Growth inhibition induced by short hairpin RNA to silence survivin gene in human
      pancreatic cancer cells.
AB  - BACKGROUND: Survivin is known to be overexpressed in various human malignancies,
      including pancreatic cancer, and mediates cancer cell proliferation and tumor
      growth, so the regulation of this molecule could be a new strategy for treating
      pancreatic cancer. In this study, short hairpin RNAs (shRNAs) specific to
      survivin were introduced into human pancreatic cancer Patu8988 cells to
      investigate the inhibitory effects on survivin expression and cell proliferation
      in vitro and in vivo. METHODS: Three kinds of shRNA specific to the survivin gene
      were designed and cloned into eukaryotic expression plasmid pGenesil-1 vector.
      Subsequently the recombinant plasmids were transfected into human pancreatic
      cancer Patu8988 cells with lipfectamineTM 2000 reagent. The mRNA and protein
      expressions of survivin in the transiently transfected Patu8988 cells were
      determined by RT-PCR, flow cytometry, and Western blotting analysis. The
      proliferation inhibition rates of stably transfected Patu8988 cells were
      determined by MTT assay. The antitumor activities of the three kinds of survivin
      shRNA plasmids were evaluated in BALB/c nude mice inoculated with Patu8988 cells
      and bearing human pancreatic cancer. RESULTS: The three survivin-shRNA plasmids
      named pGenesil-1-survivin-1, pGenesil-1-survivin-2 and pGenesil-1-survivin-1+2
      (with double interfering RNA sites) were successfully constructed, and were
      confirmed by restriction enzyme cutting and sequencing. At 48 hours after
      transfection, the expression of survivin mRNA and protein was inhibited in
      Patu8988 cells transfected with pGenesil-1-survivin-1, pGenesil-1-survivin-2, and
      pGenesil-1-survivin-1+2 when compared with that of either pGenesil-1-NC (with
      scrambled small interfering RNA) transfected cells or control cells (P<0.05). The
      MTT results showed that the proliferation rates of Patu8988 cells stably
      transfected with survivin-shRNA plasmids were reduced when compared with that of
      either pGenesil-1-NC transfected cells or control cells (P<0.01). Furthermore,
      when Patu8988 cells stably transfected with survivin-shRNA were injected into
      BALB/c nude mice, tumor growth was dramatically lower and the tumor was smaller
      than that of either pGenesil-1-NC transfected cells or control cells (P<0.01).
      The inhibitory effect of pGenesil-1-survivin-1 was the best among the three kinds
      of survivin-shRNA plasmids, but no combination of inhibitory effects was found in
      pGenesil-1-survivin-1+2. CONCLUSIONS: shRNAs specific to survivin have gene
      silencing effects and inhibit pancreatic cancer cell proliferation. shRNA
      activity against survivin could be of potential value in gene therapy for
      pancreatic cancer. However, shRNAs with double combining sites did not
      significantly enhance the interference compared with single site shRNAs,
      therefore further studies on this are needed.

PMID- 20133234
TI  - Oxidative stress and lipid peroxidation products: effect of pinealectomy or
      exogenous melatonin injections on biomarkers of tissue damage during acute
      pancreatitis.
AB  - BACKGROUND: Melatonin (N-acetyl-5-methoxytripta-mine) is a free radical scavenger
      and a strong antioxidant, secreted by the pineal gland. In this study, we
      evaluated the effects of decreasing and increasing serum melatonin levels on
      malonyldialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione
      (GSH) levels in pancreatic tissue from rats with experimental acute pancreatitis.
      METHODS: Experimental acute pancreatitis was induced in three groups of Wistar
      albino rats (10 animals per group) by pancreatic ductal ligation. The first group
      had only acute pancreatitis and served as the control. Surgical pinealectomy was
      added to acute pancreatitis in the second group, removing the source of
      endogenous melatonin (low melatonin levels group). The third group was given 0.1
      ml daily intraperitoneal injections of 20 mg/ml melatonin solution for one week
      (high melatonin levels group). The effects of melatonin levels were evaluated by
      comparison of the levels of MDA, SOD, and GS in pancreatic tissue. RESULT: We
      found that intraperitoneal melatonin injections decreased the levels of MDA and
      increased the levels of SOD and GSH in pancreatic tissue. CONCLUSION: Exogenous
      melatonin has a preventive effect on lipid peroxidation and oxidative damage in
      acute pancreatitis.

PMID- 20133235
TI  - Pathological changes at early stage of multiple organ injury in a rat model of
      severe acute pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis (SAP) is a commonly seen acute abdominal
      syndrome characterized by sudden onset, rapid progression and high mortality
      rate. The damage in peripheral organs may be more severe than that in the
      pancreas, and can even lead to multiple organ dysfunction. It is critical to
      recognize early pathological changes in multiple organs. This study aimed to
      assess the early pathological features of damaged organs in a rat model of SAP.
      METHODS: Thirty clean grade healthy male Sprague-Dawley rats weighing 250-300 g
      were randomly divided into a model control group (n=15) and a sham-operated group
      (n=15). The SAP rat model was induced by sodium taurocholate. Samples of blood
      and from multiple organs were collected 3 hours after operation. We assessed the
      levels of IL-6, TNF-alpha, PLA2, NO, ET-1, MDA, amylases and endotoxin in blood
      and observed the early pathological changes in multiple damaged organs. RESULTS:
      Levels of IL-6, TNF-alpha, PLA2, NO, ET-1 and MDA in serum and of amylase and
      endotoxin in plasma of the model control group rats were significantly higher
      than those of the sham-operated group (P<0.01). Different degrees of pathological
      change were observed in multiple damaged organs. CONCLUSION: Multiple organ
      injury may occur at the early stage of SAP in rats.

PMID- 20133236
TI  - Contrast-free air cholangiography-assisted unilateral plastic stenting in
      malignant hilar biliary obstruction.
AB  - BACKGROUND: Endoscopic palliation in malignant hilar biliary obstruction requires
      endoscopic retrograde cholangiopancreatography (ERCP), whereas contrast injection
      leads to cholangitis. Contrast-free metal stenting with or without magnetic
      resonance cholangiopancreatography (MRCP) has shown encouraging results, but MRCP
      and metal stents are costly. There have been no reports on the use of air
      cholangiography. METHODS: We prospectively evaluated the role of air
      cholangiography-assisted unilateral plastic stenting in 10 patients with type II
      malignant hilar biliary obstruction. A retrospectively analysed group of 10
      patients treated with contrast-free unilateral metal stenting served as
      historical controls. RESULTS: Ten patients with unresectable type II malignant
      hilar biliary obstruction were studied. Air cholangiography detected type II
      obstruction in all patients, similar to MRCP. The patients underwent unilateral
      stenting. Successful endoscopic drainage was achieved in all patients. The mean
      patency of the stent was 95.8+/-17.5 days in the study group and 143.9+/-115.1
      days in the control group (P=0.20). The mean survival was 121.8+/-41.6 days in
      the study group and 154.9+/-122.5 days in the control group (P=0.42). Kaplan
      Meier analysis showed an estimated median survival of 100:95% CI (65.9, 134.1)
      days in the study group and 98:95% CI (84.1, 111.9) days in the control group
      (P=0.62). Cholangitis occurred in none of the patients and there were no 30-day
      deaths nor major complications. Air cholangiography-assisted unilateral plastic
      stenting was cheaper than contrast-free unilateral metal stenting. CONCLUSION:
      Air cholangiography-assisted unilateral plastic stenting is as safe and effective
      as contrast-free unilateral metal stenting in type II malignant hilar biliary
      obstruction for palliating patients, but it is cheaper.

PMID- 20133237
TI  - Liver transplantation for acute intermittent porphyria: a viable treatment?
AB  - BACKGROUND: Acute intermittent porphyria (AIP) is the most common hepatic
      porphyria. Its clinical presentation includes severe disabling and life
      threatening neurovisceral symptoms and acute psychiatric symptoms. These symptoms
      result from the overproduction and accumulation of porphyrin precursors, 5
      aminoleuvulinic acid (ALA) and porphobilinogen (PBG). The effect of medical
      treatment is transient and is not effective once irreversible neurological damage
      has occurred. Liver transplantation (LT) replaces hepatic enzymes and can restore
      normal excretion of ALA and PBG and prevent acute attacks. METHOD: Two cases of
      LT for AIP were identified retrospectively from a prospectively maintained LT
      database. RESULT: LT was successful with resolution of AIP in two patients who
      suffered from repeated acute attacks. CONCLUSION: LT can correct the underlying
      metabolic abnormality in AIP and improves quality of life significantly.

PMID- 20133238
TI  - Synchronous gastric adenocarcinoma and pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: The association between gastric and pancreatic carcinoma is a
      relatively rare condition. In gastric carcinoma patients, the prevalence of
      second tumors varies 2.8% to 6.8% according to the reported statistics. Gastric
      cancer associated with pancreatic cancer is uncommon. METHODS: We report a case
      of a 73-year-old patient hospitalized for vomiting and weight loss.
      Esophagogastroduodenoscopy demonstrated an ulcerative lesion of the gastric
      antrum. Computed tomography and magnetic resonance showed a gastric thickening in
      the antral and pyloric portion and a nodular mass (3 X 1.7 cm) in the uncinate
      portion of the pancreas. RESULTS: The patient underwent pancreaticoduodenectomy
      according to Whipple regional type I Fortner. Histological examination of the
      specimen demonstrated a moderately differentiated adenocarcinoma of the stomach
      and a poorly differentiated ductal adenocarcinoma of the pancreas. CONCLUSIONS:
      Long survival is rare in patients with associated gastric and pancreatic cancer.
      Surgical resection remains the only potentially curative treatment.

PMID- 20133239
TI  - Thrombosis of gallbladder vein presenting as acute peritonitis.
AB  - BACKGROUND: Thrombosis of the gallbladder vein occurs rarely, and few clinical
      features have been reported. We report here with a case of gallbladder vein
      thrombosis presenting as acute peritonitis in a 75-year-old man. METHODS: The old
      man with sudden continuous abdominal pain resorted to the emergency room and
      treated for peritonitis associated with acute cholecystitis. The treatment failed
      to slow the progress of the disease, and massive ascites appeared with thickening
      of the gallbladder wall. Laparotomic investigation was conducted later. RESULT:
      Pathologically, thrombosis of the gallbladder vein was diagnosed. CONCLUSIONS:
      The thrombosis of the gallbladder vein is characterized by thickening of the
      gallbladder wall, ascites, and sudden continuous abdominal pain. The causes of
      deep vein thrombosis at this unusual site vary.

PMID- 20133240
TI  - Acinar cell carcinoma of the pancreas in a young patient with chronic
      pancreatitis.
AB  - BACKGROUND: Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas
      arising from acinar cells. Unlike ductal adenocarcinoma, this tumor rarely
      presents with pancreatitis. METHODS: We present a case of ACC associated with
      chronic calcifying pancreatitis, and a review of the literature focusing on
      diagnosis and management. RESULTS: A 43-year-old man was proposed for
      Wirsungojejunal derivation for chronic pancreatitis. Histopathological
      examination of the tissue extracted revealed an ACC. Duodenopancreatectomy was
      performed. Six months post-operatively, the patient developed hepatic metastasis
      and was treated with gemcitabine as palliative chemotherapy. CONCLUSIONS: The
      clinical presentation of ACC of the pancreas is not specific and the tumor can be
      under-diagnosed when associated with chronic pancreatitis. Data regarding course,
      treatment, and prognosis of this tumor are generally lacking.

PMID- 20133241
TI  - Gallbladder and cystic duct agenesis diagnosed laparoscopically.

PMID- 20133242
TI  - Melanoma of the gallbladder misdiagnosed as gallbladder cancer.

PMID- 20133243
TI  - [Fabry disease--diagnostic guideline].
AB  - Fabry disease is a rare, X-linked lysosomal storage disorder that leads to
      accumulation of globotriaosylceramide in different tissues of the body. The
      disease is progressive, first symptoms usually present in childhood.
      Consequencies of the diseases are disability and premature death. The disease in
      females could be as severe as in males although women may also be asymptomatic.
      The possibility of enzyme replacement therapy has made it necessary to elaborate
      a comprehensive guideline for the diagnosis and treatment follow-up. The
      guideline was established by a Hungarian multi-disciplinary working group,
      consisting of physicians who are involved in health care of Fabry patients.
      Previous clinical studies, published materials, and recently established
      international treatment guidelines were reviewed by the group.

PMID- 20133244
TI  - [Treatment adherence and use of complementary and alternative medicine in
      patients with inflammatory bowel disease].
AB  - Previous studies have suggested an increasing use of complementary and
      alternative medicine (CAM) in patients with inflammatory bowel disease (IBD).
      Furthermore, a significant number of IBD patients fail to comply with treatment.
      The aim of our study was to evaluate the prevalence of non-adherence the use of
      CAM in Hungarian patients with IBD. METHODS: A total of 655 consecutive IBD
      patients (Crohn's disease [CD]: 344, age: 38.2 + or - 12.9 years; ulcerative
      colitis [UC]: 311, age: 44.9 + or - 15.3 years) were interviewed during the visit
      at specialists by self-administered questionnaire including demographic and
      disease-related data, as well as items analyzing the extent of non-adherence and
      CAM use. Patients taking more then 80% of each prescribed medicine were
      classified as adherent. RESULTS: The overall rate of self reported non-adherence
      (CD: 20.9%, UC: 20.6%) and CAM (CD: 31.7%, UC: 30.9%) use was not different
      between CD and UC. The most common causes of non-adherence were: forgetfulness
      (47.8%), too many/unnecessary pills (39.7%), being afraid of side effects (27.9%)
      and too frequent dosing. Most common forms of CAM were herbal tee (47.3%),
      homeopathy (14.6%), special diet (12.2%), and acupuncture (5.8%). In CD, disease
      duration, date of last follow-up visit, educational level and previous surgeries
      were predicting factors for non-adherence. Alternative medicine use was
      associated in both diseases with younger age, higher educational level and
      immunosuppressant use. In addition, CAM use in UC was more common in females and
      in patients with supportive psychiatric/psychological therapy. CONCLUSIONS: Non
      adherence and CAM use is common in patients with IBD. Special attention should be
      paid to explore the identified predictive factors during follow-up visits to
      improve adherence to therapy and improving patient-doctor relationship.

PMID- 20133245
TI  - [Screening and treatment for retinopathy of prematurity at the Markusovszky
      County Hospital, (experience of 20 years: 1989-2009].
AB  - The aims of this study was to obtain the frequency and therapy of retinopathy of
      prematurity (ROP) in Markusovszky Teaching Hospital, Szombathely, Hungary. A
      population based study on ophthalmological status of preterm infants was
      performed, between 01.01.1989 and 01.01.2009. During the study period,
      ophthalmological status was detected in 543 premature infants. Among them, 34
      children (6.3%) suffered from retinopathy of prematurity, and all of them were
      bilateral. ROP occurred in the highest rate (23/78 cases, 29.5%) at the birth
      weight of lower than 1000 grams, but frequency was only l.2% (2/169 cases)
      between weight 1250-1500 grams. Spontaneous recovery was observed in 19 eyes of
      10 cases. The frequency of spontaneous resolution was 40% and 50% in the group of
      larger birth weight: between 1251-1500 grams and weight > or = 1500 grams, but on
      the other hand, complete recovery was only 26% (6/23 cases) below 1000 grams of
      birth weight. "Threshold retinopathy" (stage 3 plus), that needed therapy was
      detected in 25 children's 49 eyes. Cryotherapy was performed in both eyes of 16
      children (32 eyes), laser photocoagulation was performed in 9 patients (16 eyes).
      ROP regressed after cryotherapy in 26 eyes, but in 6 eyes symptoms progressed to
      stage 5. After laser photocoagulation, recovery was observed in 16 eyes; this
      therapy was not successful in only one case. According to our experiences, stage
      5 ROP developed only in two patients' both eyes, and in 1-1 eye of three
      children, during the 20 years of study. Our ophthalmological screening program
      proved that providing cryopexia or laser photocoagulation in time, severe visual
      impairment of retinopathy can be prevented. In spite of the few number of
      patients, this population based investigation with a long duration (20 years)
      offers new data in Hungarian ROP epidemiology.

PMID- 20133246
TI  - [Analysis of clinical course of severe acute biliary and non biliary
      pancreatitis: a comparative study].
AB  - The acute pancreatitis is a relative common disease with incidence of 5-80 per
      100000 people of the population. The number of new cases has steadily increased
      in recent years. The two main etiological factors are alcohol and cholelithiasis.
      The incidence of alcoholic pancreatitis is higher in male, and the incidence of
      gallstone pancreatitis is higher in female. AIM: To summarize the difference
      between the clinical course of biliary and not biliary type of severe acute
      pancreatitis by analyzing the data of these patients. METHODS: 139 patients
      treated with severe acute pancreatitis were divided in two groups: biliary (A
      group) and non biliary (B group) of origin. The two groups were compared on the
      basis of sex and age, mortality, morbidity, number of surgery and hospital stay.
      chi 2 probe was used for the statistical analysis. RESULTS: The complications in
      biliary group were more serious. The average mortality rate was 15.1%, 17.8% in
      group A and 13.8% in group B. The mortality rate of female patients in group A
      was significantly higher. CONCLUSION: Female patients suffering from severe
      biliary acute pancreatitis have higher morbidity and mortality rate. Therefore an
      elective cholecystectomy is suggested in old female patients with serious co
      morbidity and gallstones, before any complications.

PMID- 20133247
TI  - [Peginterferon-alfa-2b or -alfa-2a and ribavirin combined treatment in hepatitis
      C infection].

PMID- 20133249
TI  - Nipple-sparing skin-sparing mastectomy and vertical latissimus dorsi flap
      reconstruction for bilateral fibromatosis of the breast.
AB  - Fibromatosis of the breast results in aggressive, infiltrative lesions with a
      tendency for local recurrence. A case of bilateral fibromatosis of the breast
      treated with nipple-sparing skin-sparing mastectomy and vertical latissimus dorsi
      flap reconstruction occurring in 22-year-old woman is described herein.

PMID- 20133250
TI  - Metastatic prostatic adenocarcinoma mimicking inflammatory breast carcinoma: a
      case report.
AB  - Prostate adenocarcinoma can manifest as a fairly indolent tumor or as a very
      aggressive cancer with significant invasive and metastatic potential. Common
      metastatic sites include bone, liver, lymph nodes, and adrenal glands.
      Dermatologic manifestations are rare. We present a case of a man who presented
      with breast skin changes that mimicked inflammatory breast carcinoma with
      specialized testing ultimately giving a diagnosis of metastatic prostatic
      adenocarcinoma. A 78-year-old man presented with left breast redness and
      swelling. Examination revealed an erythematous rash with subcutaneous edema over
      the left hemithoracic area. A breast ultrasound showed no focal mass, and a
      breast core biopsy had no evidence of tumor. A skin biopsy showed metastatic
      carcinoma in dermal lymphatics, and the tumor was found to have no estrogen or
      progesterone receptors or HER2 expression. Computed tomography scans, positron
      emission tomography, and a nuclear bone scan revealed widespread skeletal
      metastases. The patient received a 3-month course of capecitabine and
      cyclophosphamide with no improvement in his skin lesions. Subsequent
      immunohistochemical staining on the tumor specimen was positive for prostate
      specific antigen (PSA) and alpha-methyl-CoA-racemase, confirming a diagnosis of
      metastatic prostatic adenocarcinoma. He received leuprolide and bicalutamide and
      demonstrated significant improvement with near-complete resolution of his skin
      lesions and a decrease in his PSA level. Prostatic adenocarcinoma presenting
      initially as a breast malignancy is a rarely recognizable clinical event.
      Undoubtedly, increased awareness and recognition of the rare entity described
      herein will allow for the prompt initiation of specific therapies, which might be
      of benefit to many patients.

PMID- 20133251
TI  - Understanding resistance to endocrine agents: molecular mechanisms and potential
      for intervention.
AB  - BACKGROUND: We developed a mouse model system that mimics hormone-dependent
      postmenopausal breast cancer. In this model, human estrogen receptor-positive
      (ER+) breast cancer cells (MCF-7) stably transfected with aromatase (MCF-7Ca) are
      grown as tumors in ovariectomized female nude mice. Using this model, we have
      established that aromatase inhibitors (AIs) such as letrozole and anastrozole
      that reduce estrogen production are more effective than the antiestrogen agent
      tamoxifen. This intratumoral aromatase xenograft model has proved accurate in
      predicting the outcome of several clinical trials. Nevertheless, resistance to
      treatment might eventually occur. MATERIALS AND METHODS: To investigate the
      mechanisms involved in the loss of sensitivity of the tumors to AIs, we developed
      a cell line isolated from the tumors of long-term letrozole-treated MCF-7Ca
      xenografts. This cell line was designated LTLT-Ca. RESULTS: These cells exhibited
      lower expression of ERalpha and apparent "estradiol-independent" growth along
      with hyperactivation of growth factor receptor- mediated signaling pathways such
      as HER2/mitogen-activated protein kinase. The inhibition of HER2 with trastuzumab
      results in restoration of ERalpha and response to letrozole. CONCLUSION: Our data
      suggest that inhibition of both the HER2 and estrogen signaling pathways is
      required to prolong the responsiveness of the tumors to endocrine therapies. In
      addition, we have shown that HER2 upregulation is an adaptive process that the
      tumors undergo during continued letrozole treatment, which is reversed upon
      removal of the treatment. The tumors regain responsiveness to letrozole after a
      short period "off" treatment. These studies suggest that by reversing the
      resistance to hormone therapy, patients could have a second response and could
      delay the need for chemotherapy.

PMID- 20133253
TI  - Where to with HER2?

PMID- 20133255
TI  - Inflammatory breast cancer: novel preoperative therapies.
AB  - The treatment of inflammatory breast cancer (IBC) has been hampered by the
      diagnostic rarity of the disease and its consequent inclusion in clinical trials
      of preoperative treatment for the more indolent locally advanced breast cancer
      (LABC). Patients with IBC have a 2-fold greater probability of dying of their
      disease compared with patients diagnosed with LABC. The aggressive clinical
      portrait of IBC supports the recent investigative focus on determining molecular
      changes specific to IBC and developing novel systemic therapies that will
      favorably affect its poor disease prognosis. A significant amount of laboratory
      research has been involved in defining a specific "inflammatory signature" for
      IBC, denoting molecular changes consistently found in IBC. This work has involved
      human IBC tissue and cell lines and has demonstrated overexpression of several
      molecules governing metastatic dissemination, such as overexpression of E
      cadherin concurrent with a dysfunctional mucin 1. An increased prevalence of
      mutant TP53, overexpression of RhoC, and vascular endothelial growth factor-A has
      been found to contribute to the dominant influence of angiogenesis in this
      disease. A greater understanding of the molecular mechanisms governing the
      pathophysiology of IBC has led to the development and clinical application of
      novel targeting agents for preoperative therapy. This study reviews the advances
      in molecular understanding of IBC and focuses on the efficacy of therapies that
      target the epidermal growth factor pathway and angiogenesis as well as early
      investigational therapies involving RhoC and TP53.

PMID- 20133256
TI  - Intravenous bisphosphonate therapy does not acutely alter nuclear bone scan
      results.
AB  - INTRODUCTION: Theoretically, the bisphosphonates used to treat metastatic bone
      disease could influence the results of nuclear bone scans which use the
      structurally similar technetium 99m methylene diphosphonate (99mTc MDP). A
      prospective clinical study was designed to explore this hypothesis. PATIENTS AND
      METHODS: Patients with metastatic breast cancer receiving intravenous
      bisphosphonate (IVBP) therapy who had > or =3 osseous lesions on nuclear bone
      scan were eligible. A baseline bone scan (number 1) was performed as clinically
      indicated and IVBP with zoledronic acid was administered within 72 hours. A
      second bone scan (number 2) was performed within 72 hours of zoledronic acid
      dosing. Both bone scans were reviewed in a blinded fashion and assessed for
      changes in the number and intensity of osseous lesions. Ten patients were planned
      to yield at least 30 lesions. RESULTS: Ten patients were enrolled. One patient
      withdrew consent and 1 was excluded due to protocol deviation. Among the 8
      patients were 163 assessable osseous lesions. The median time from bone scan
      number 1 to IVBP was 1 day (range, 1-2 days). The median time from IVBP to bone
      scan number 2 was 2 days (range, 1-3 days). The paired imaging showed no changes
      in the total number of bone metastases. One hundred sixty-one lesions were
      identical in both scans; in 1 patient there were 2 lesions that were discordant,
      one more intense, the other less intense. CONCLUSION: These data do not support
      the hypothesis that IVBP therapy interferes with bone scan results.

PMID- 20133257
TI  - Pathologic complete response to preoperative sequential
      doxorubicin/cyclophosphamide and single-agent taxane with or without trastuzumab
      in stage II/III HER2-positive breast cancer.
AB  - BACKGROUND: Four major clinical trials have established that trastuzumab added to
      adjuvant systemic chemotherapy for women with HER2+ breast cancer significantly
      improves disease-free and overall survival compared with chemotherapy alone. We
      evaluated pathologic complete response (pCR) rate and cardiac safety of
      preoperative doxorubicin and cyclophosphamide followed by a taxane with or
      without trastuzumab. PATIENTS AND METHODS: We reviewed pCR rate and change in
      left ventricular ejection fraction in women with operable HER2+ breast cancer
      (defined as immunohistochemical 3+ or fluorescence in situ hybridization ratio >
      or = 2.2) who were treated between 2002 and 2008 with doxorubicin and
      cyclophosphamide followed by a taxane with or without trastuzumab before
      definitive breast surgery. RESULTS: We identified 33 patients, of whom 42.4%
      received preoperative chemotherapy without trastuzumab and 57.6% of whom received
      trastuzumab with chemotherapy. The pCR rates were 28.6% and 52.6% in the group
      that received chemotherapy alone or with trastuzumab, respectively (odds ratio,
      2.78; 95% CI, 0.64-12.1; P = .173). Severe cardiac events or treatment delays as
      a result of cardiac toxicity were not observed. With a median follow-up time of
      14 months, 21.4% of patients in the non-trastuzumab group and 10.5% in the
      trastuzumab group had disease recurrence. CONCLUSION: Sequential administration
      of preoperative doxorubicin and cyclophosphamide followed by a taxane and
      trastuzumab combination is safe in women with primary operable HER2+ breast
      cancer and is associated with a high pCR rate. Large randomized phase III
      clinical trials are evaluating the role of preoperative trastuzumab when added to
      anthracycline- and/or taxane-based regimens.

PMID- 20133258
TI  - Clinical outcomes of patients with breast cancer in a phase I clinic: the M. D.
      Anderson cancer center experience.
AB  - PURPOSE: Patients with metastatic breast cancer (MBC) refractory to standard
      therapy have a poor prognosis. We assessed prognostic factors and clinical
      outcomes for patients with MBC referred to a phase I clinic focused primarily on
      targeted agents. PATIENTS AND METHODS: We reviewed the medical records of
      sequential patients with MBC who presented to our phase I clinic between
      September 2004 and May 2008 to assess baseline patient characteristics, overall
      survival (OS), and clinical benefit. RESULTS: A total of 92 patients were
      identified, with a median age of 53 years (range, 28-83 years). The median number
      of previous therapies was 5 (range, 1-16 therapies). Of 92 patients, 78 were
      eligible for and offered > or = 1 phase I clinical trial. With a median follow-up
      of 7.4 months, the median OS was 6.7 months (95% CI, 5.2-9.7). In multivariate
      analysis, independent factors predicting shorter survival were > or = 10 previous
      treatments (vs. < 10 previous treatments; hazard ratio [HR], 3.27; 95% CI, 1.37
      7.81; P = .008), Eastern Cooperative Oncology Group (ECOG) performance status
      (PS) 2/3 (vs. 0/1; HR, 2.92; 95% CI, 1.28-6.66; P = .01), and albumin level < 3.5
      g/dL (vs. > 3.5 g/dL; HR, 2.88; 95% CI, 1.41-5.89; P = .004). CONCLUSION:
      Patients with locally advanced or metastatic breast cancer referred for our phase
      I studies had a median survival of 6.7 months. Heavily pretreated disease, poor
      ECOG PS, and/or low albumin levels were associated with significantly shorter
      survival in a multivariate analysis.

PMID- 20133259
TI  - Clinicopathologic factors associated with involved margins after breast
      conserving surgery for invasive lobular carcinoma.
AB  - INTRODUCTION: Obtaining negative margins for patients undergoing breast
      conserving surgery (BCS) for invasive lobular carcinoma (ILC) can be difficult
      because of the unique histologic pattern of ILC. Our goal was to determine
      whether any specific patient- or disease-related factors influenced margin
      status. PATIENTS AND METHODS: We retrospectively reviewed 211 patients with ILC
      treated from 1994 through 2004 to determine if specific clinical and pathologic
      factors influenced the ability to obtain negative margins. RESULTS: We identified
      110 patients (52%) who underwent total mastectomy and 101 (48%) who underwent
      BCS. Among patients who underwent BCS, 50 (50%) had close or positive margins.
      Patients with close or positive margins were more likely to have architectural
      distortion on ultrasonography (vs. mass or calcifications; P = .049), to have
      undergone excisional biopsy (vs. core or fine-needle aspiration; P = .008), and
      to have associated ductal carcinoma in situ (P = .021). On multivariate analysis,
      only biopsy method retained significance (P = .006). CONCLUSION: Core needle
      biopsy is the preferred method of diagnostic biopsy before surgical intervention.
      With appropriate patient selection, most patients with early-stage ILC can
      undergo successful BCS.

PMID- 20133260
TI  - Race as an independent risk factor for breast cancer survival: breast cancer
      outcomes from the medical college of georgia tumor registry.
AB  - BACKGROUND: Causes of racial disparities in breast cancer survival remain
      unclear. This study assesses overall survival (OS) after diagnosis between black
      and white women and examines factors that might correlate with this disparity.
      PATIENTS AND METHODS: Data were obtained from the Medical College of Georgia
      Tumor Registry. Cases included those diagnosed between 1990 and 2005. We analyzed
      race, stage, age of diagnosis, and treatment received: chemotherapy, radiation,
      surgery, and hormonal therapy. A Cox proportional hazards model was used to
      determine differences in OS. RESULTS: Compared with 670 white women, 489 black
      women were more likely to be younger, have later-stage disease at diagnosis, and
      were less likely to have received hormonal therapy. Both groups received similar
      rates of radiation, surgery, and chemotherapy. Black women had significantly
      poorer OS (adjusted hazard ratio, 1.35; 95% CI, 1.12-1.63). White women had a 5
      year OS of 54% compared with 45% in black women (P = .0031). Having received
      radiation, surgery, or chemotherapy was not associated with OS. White women were
      more likely to have received hormonal therapy, which had a significant protective
      effect. However, a stratified analysis (between those who received hormonal
      therapy and those who did not) showed similar results, whereas black women
      experienced poorer OS in both strata. CONCLUSION: Black women with breast cancer
      had a significantly poorer OS compared with white women. White women received
      more hormonal therapy, which had a protective effect. There were no differences
      in treatment received regarding radiation, surgery, or chemotherapy, and these
      treatments were not associated with OS. The reasons for racial disparities in
      breast cancer OS remain complex.

PMID- 20133261
TI  - Visceral disease in patients with metastatic breast cancer: efficacy and safety
      of treatment with ixabepilone and other chemotherapeutic agents.
AB  - Patients with metastatic breast cancer (MBC) have poor prognoses and 5-year
      survival rates of approximately 20%. The site(s) and degree of metastatic
      dissemination are among the principal prognostic factors for patients with MBC.
      Patients with visceral metastases to the liver and/or lung have a very poor
      prognosis. Although good performance status, restricted disease dissemination,
      and limited extent of metastatic infiltration are associated with higher
      responses to chemotherapy, responses are generally short lived, with rapid
      disease progression after treatment failure. Thus, novel strategies for the
      management of patients with MBC with visceral disease are urgently needed. We
      have analyzed outcomes of trials that evaluated various chemotherapeutic agents
      as monotherapy or in combination with capecitabine in patients with MBC with
      primary visceral disease involvement. Treatment with microtubule inhibitors such
      as paclitaxel, docetaxel, and albumin-bound paclitaxel, generally administered in
      earlier lines of treatment, resulted in comparable responses. Lower response
      rates (RRs) were reported with other agents such as capecitabine, vinorelbine,
      and gemcitabine. Adverse events consistent with known toxicities of each agent
      were observed in the selected trials and related to dose and administration
      schedule. The epothilone B analogue ixabepilone has demonstrated clinical
      efficacy and manageable safety in populations of heavily pretreated patients with
      MBC with high visceral disease burdens to liver and/or lung (61%-86% of
      patients). Objective RRs ranging from 12% to 57% have been reported for
      ixabepilone, as monotherapy and in combination with capecitabine, depending on
      degree of pretreatment. Responses to ixabepilone in patients with visceral
      metastases were comparable to those observed in overall study patient
      populations.

PMID- 20133262
TI  - Role of anemia prior to radiation treatment in local recurrence and survival
      after breast conservation treatment for early-stage breast cancer.
AB  - BACKGROUND: Anemia is common among patients with newly diagnosed cancer, may be
      exacerbated by cancer therapies, and leads to radioresistance by lowering oxygen
      levels in the tumor microenvironment. Herein, the effect of breast irradiation on
      hemoglobin levels and outcomes in breast conservation therapy is reported.
      PATIENTS AND METHODS: Medical records of 1368 women with stage 0, I, and II
      breast cancer treated with breast conservation therapy from 1977-2002 were
      reviewed. Hemoglobin levels at baseline as well as during and after radiation
      were recorded. Patterns of hemoglobin changes and the effect of anemia on local
      control and survival outcomes were assessed. Median follow-up time was 8 years
      for the normal group and 6 years for the anemic group. RESULTS: Baseline anemia
      was seen in 18% of the patients, 90% of whom had mild anemia (hemoglobin, 11.9
      10.0 g/dL). Anemia was recorded in 21% during radiation. Among patients with
      normal baseline hemoglobin levels, 6.5% of the patients became anemic during
      radiation. Of those with baseline anemia, 72% had stable to improved hemoglobin
      levels during radiation, and 22% declined by a median of 0.3 g/dL. There were no
      significant differences in local or regional recurrence, overall, disease-free,
      cause-specific, or distant disease-free survival between patients with baseline
      anemia or with normal hemoglobin. CONCLUSION: Radiation does not contribute
      significantly to anemia during breast conservation treatment, and mild anemia
      does not affect outcomes. It is unnecessary to obtain routine hemoglobin levels
      during radiation therapy. There is no difference in outcomes based on hemoglobin
      levels; thus, there is no reason to transfuse or provide erythropoiesis
      stimulating agents for hemoglobin levels > 10 g/dL during radiation treatment of
      the breast.

PMID- 20133263
TI  - A phase II neoadjuvant trial of sequential nanoparticle albumin-bound paclitaxel
      followed by 5-fluorouracil/epirubicin/cyclophosphamide in locally advanced breast
      cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy has become standard treatment for women with
      locally advanced breast cancer (LABC). Various regimens have explored the
      addition of newer agents to determine safety and efficacy. The aim of this phase
      II study was to incorporate albumin-bound paclitaxel with sequential
      anthracycline-based therapy. PATIENTS AND METHODS: Sixty-six women with LABC but
      without prior treatment and regardless of hormone receptor or HER2 status were
      enrolled. All patients were to receive albumin-bound paclitaxel weekly for 12
      weeks followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) every 3 weeks
      for 4 cycles. Trastuzumab was allowed in HER2-positive (HER2+) patients. Primary
      endpoint was pathologic complete response (pCR; CR) in breast. Secondary
      endpoints included pCR in breast and nodes, clinical CR, 2-year progression-free
      survival, and overall survival. RESULTS: Sixty-five patients received at least 1
      dose of chemotherapy and were included in this analysis. Sixty-three patients
      completed 4 cycles of albumin-bound paclitaxel. Sixty-two patients received at
      least 1 dose of FEC, and 58 completed 4 cycles. Seventeen of 19 HER2+ women
      received trastuzumab. The pCR in breast was 29% (19 of 65). For the HER2+ subset,
      the pCR was 58% (11 of 19). Both albumin-bound paclitaxel and FEC were well
      tolerated. The most significant toxicities were grade 2/3 neuropathy (16%) with
      albumin-bound paclitaxel and grade 3/4 febrile neutropenia (7%) with FEC.
      CONCLUSION: Albumin-bound paclitaxel given over 12 weeks is well tolerated.
      Albumin-bound paclitaxel should be further evaluated in a randomized setting in
      both adjuvant and neoadjuvant trials.

PMID- 20133265
TI  - Long-term impact of efavirenz on neuropsychological performance and symptoms in
      HIV-infected individuals (ACTG 5097s).
AB  - BACKGROUND: Efavirenz (EFV) is an antiretroviral (ARV) drug associated with
      neuropsychological effects. Limited data describing the long-term impact of EFV
      based regimens on neuropsychological performance over more than 3 years are
      available. METHODS: We enrolled a subset of participants from a large initially
      EFV placebo-controlled trial of therapies for HIV subjects naive to ARV treatment
      (A5095). Clinical follow-up continued for 184 weeks of study. Subjects were
      assessed with brief neuropsychological testing, a symptom questionnaire of EFV
      associated symptoms, the Pittsburgh Sleep Index, Center for Epidemiologic Studies
      Depression Scale, and an anxiety rating interview. RESULTS: Over 184 weeks on
      EFV, the median NPZ3 score in 86 evaluable patients improved from baseline by
      +0.5 (p < .01); all components improved, although higher EFV levels were
      associated with slightly lower responses. Overall symptom scores did not change,
      while EFV-associated CNS symptoms increased (p = .01). Median change of bad dream
      sleep scores and anxiety increased from the baseline while global depression
      score decreased. CONCLUSIONS: In participants who continued EFV-based regimens,
      neuropsychological performance improvement from baseline was maintained over 3
      years. EFV-based treatment was generally well tolerated, but small increases from
      baseline in EFV-associated symptoms, bad dreams, and anxiety were detected.

PMID- 20133266
TI  - Study of once-daily versus twice-daily fosamprenavir plus ritonavir administered
      with abacavir/lamivudine once daily in antiretroviral-naive HIV-1-infected adult
      subjects.
AB  - PURPOSE: Fosamprenavir/ritonavir 1400 mg/100 mg once-daily regimen may have a
      more favourable tolerability and lipid profile than the fosamprenavir/ritonavir
      twice-daily regimen, while maintaining comparable antiviral efficacy. METHODS:
      This open-label study had a group-sequential design with a stage 1 Week 24
      futility analysis, with both efficacy and safety go-criteria for progression to
      stage 2. There were 214 antiretroviral-naive, HIV-1-infected subjects who were
      randomised to receive either fosamprenavir/ritonavir 1400 mg/100 mg once daily or
      fosamprenavir/ ritonavir 700 mg/100 mg twice daily, both with abacavir/lamivudine
      fixed-dose combination tablet. Primary endpoints were the proportion of subjects
      achieving HIV-1 RNA <400 copies/mL at Week 48 and the mean change from baseline
      in fasting non-HDL cholesterol. RESULTS: Though stage 1 futility analysis did not
      meet criteria for progression to stage 2, subjects enrolled in stage 1 were
      followed to Week 48 per protocol. At Week 48, noninferior efficacy of once daily
      to twice daily (95% CI around the treatment difference, -11.4 to 9.5) was
      achieved, with 86/106 (81%) subjects in the once-daily and 87/106 (82%) in the
      twice-daily arm achieving HIV-1 RNA <400 copies/mL. Mean change from baseline at
      Week 48 in non-HDL cholesterol was 1.10 mmol/L and 1.26 mmol/L (p = .478) for the
      once-daily and twice-daily arms, respectively. CONCLUSION: Though the study did
      not continue to stage 2, fosamprenavir/ritonavir once daily demonstrated
      noninferior antiviral efficacy to fosamprenavir/ritonavir twice daily.

PMID- 20133267
TI  - Monotherapy with Lopinavir/Ritonavir as maintenance after HIV-1 viral
      suppression: results of a 96-week randomized, controlled, open-label, pilot trial
      (KalMo study).
AB  - BACKGROUND: Long-term adverse events and expenses associated with HAART have led
      to an interest in simplified therapy. Lopinavir/ritonavir monotherapy is
      attractive due to its potency and high genetic barrier. METHODS: This is a 96
      week, open-label, randomized study to assess the feasibility of using LPV/r
      monotherapy in patients with undetectable viral load after being on successful
      HAART for at least 6 months. Subjects were randomized (1:1) to either switch from
      HAART to LPV/r monotherapy or to maintain their previous regimen. RESULTS: 60
      patients were enrolled. Baseline characteristics were similar in both groups. At
      Week 96, by intention-to-treat analysis, 24/30 (80.0%) subjects in monotherapy
      group and 26/30(86.6%) in the control group had a plasma viral load of <80
      copies/mL. There was one virologic failure (defined as VL not greater-than 500
      copies/mL) in each arm. Genotyping testing identified no resistance-associated
      mutations. The patient on the monotherapy arm was successfully resuppressed to
      <80 copies/mL after intensification with tenofovir and lamivudine. No
      statistically significant differences were found with regard to changes in CD4
      counts. One subject in the monotherapy group discontinued due to diarrhea. Five
      subjects in the control group underwent regimen changes due to drug-related
      toxicities. Viral load from semen samples collected at the end of follow-up was
      undetectable on 14/15 patients randomized to monotherapy. CONCLUSIONS: Switching
      from various HAART regimens to LPV/r monotherapy in patients who were
      virologically suppressed and without a history of previous virologic failure was
      effective, safe, and well tolerated through 96 weeks.

PMID- 20133268
TI  - Virologic suppression, treatment adherence, and improved quality of life on a
      once-daily efavirenz-based regimen in treatment-Naive HIV-1-infected patients
      over 96 weeks.
AB  - PURPOSE: This study evaluated the long-term efficacy, safety, adherence, and
      quality of life (QoL) of a once-daily efavirenz-based antiretroviral regimen in
      two 96-week prospective open-label single-arm studies of treatment-naive HIV-1
      infected patients. METHODS: Patients received once-daily efavirenz 600 mg and
      lamivudine 300 mg with either enteric-coated didanosine 400 mg (Daily
      Antiretroviral Therapy trial [DART] I) or extended-release stavudine 100 mg (DART
      II). The primary efficacy outcome measure was HIV RNA <400 copies/mL at Week 48.
      RESULTS: In an intent-to-treat (ITT) analysis, HIV RNA level <400 (<50) copies/mL
      was reached by 82%(80%) and 74% (72%) of patients at Week 48 in DART I and II. At
      Week 96, the corresponding values were 74% (68%) and 55% (54%), respectively.
      Both regimens were well tolerated. There were no discontinuations for virologic
      failure. Medication adherence assessed by pill counts was above 80% in 90% of the
      patients in DART I and more than 80% of patients in DART II. Treatment produced a
      significant improvement in overall QoL. CONCLUSION: Once-daily efavirenz-based
      antiretroviral therapy was effective, durable, and well tolerated. In this study,
      a high level of adherence was achieved with improvement in overall QoL.

PMID- 20133270
TI  - Prevalence of CCR5-tropic HIV-1 among treatment-experienced individuals in Spain.
AB  - OBJECTIVE: To determine the prevalence of CCR5-tropic HIV-1 among treatment
      experienced patients in Spain. DESIGN: Epidemiologic, cross-sectional, and non
      interventional study between January and June 2008 in HIV-1-infected patients in
      Spain. METHODS: A total of 485 treatment-experienced patients from across
      Spainand with a plasma viral load of not greater-than1000 copies/mL were studied.
      Viral tropism, CD4+ cell count, plasma viral load, stage of disease, and current
      treatment strategies were determined. Univariate and multivariate logistic
      regression analyses were used to determine association of coreceptor use with
      patients' characteristics. RESULTS: Coreceptor usage was determined by viral
      tropism assays: 290 (68.9%) patients had CCR5-tropic HIV-1 virus, and 131 (31.1%)
      had dual-tropic/mixed or CXCR4 virus variants. Mean CD4+ cell counts in the R5
      group (319.4 cells/mm3) were higher than in the non-R5 group (237.9 cells/mm3) (p
      = .0005). There was an inverse relationship between CD4+ cell counts and plasma
      viral load, but regression analyses on covariates associated with CCR5 tropism
      showed that only a higher CD4+ cell number was significantly associated with CCR5
      coreceptor usage. CONCLUSIONS: The prevalence of CCR5-tropic HIV-1 among
      treatment-experienced patients in Spain is higher than previously found in other
      geographical settings. We did not find independent markers predictive of
      coreceptor usage other than a relationship with CD4+ levels.

PMID- 20133269
TI  - Resistance and virological response analyses in a three initial treatment
      strategy trial: a substudy of the INITIO trial.
AB  - PURPOSE: To study the impact of baseline resistance mutations and HIV-1 subtypes
      on virological response to first-line antiretroviral therapy and to analyse the
      concordance of the results of two antiretroviral resistance interpretation tools
      in the INITIO trial. METHOD: Genotype and virco TYPE resistance analyses were
      studied at baseline, Year 2, Year 3, and at first therapeutic failure on plasma
      specimens stored at -80 degrees C. Relations between resistance mutations at
      baseline, subtype, initial virological response, and virological outcome after
      Week 24 were studied. RESULTS: 781 participants had genotypic results available
      at baseline. Therapeutic failure occurred for 112 participants. Initial
      virological response as well as virological outcome after Week 24 were not
      associated with HIV subtype. Before Week 24, the proportion of participants
      remaining under strict initial regimen was lower in patients with resistance
      mutations at baseline than in those without any resistance mutations. Presenceof
      resistance mutations at baseline also impacted negatively long-term virological
      outcome. Few discrepancies were observed between genotypic and virco TYPE for
      resistance interpretation. CONCLUSION: These data showed that presence of
      resistance mutations at baseline was associated with a poorer long-term
      virological outcome in the INITIO trial.

PMID- 20133271
TI  - Effect of HCV infection on glucose metabolism in pregnant women with HIV
      receiving HAART.
AB  - OBJECTIVE: A prospective study was designed to evaluate the prevalence and
      determinants of glucose metabolism abnormalities (GMAs) among HIV-1-infected
      pregnant women receiving highly active antiretroviral therapy (HAART). METHODS:
      Blood samples were collected in fasting conditions and following a 100 g oral
      glucose tolerance test among HIV-infected pregnant women consecutively followed
      at asingle HIV reference centre in 2001-2008. GMAs were defined by glucose
      intolerance(IGT) or gestational diabetes (GDM), according to the National
      Diabetes Data Group criteria. Predictors of GMAs were assessed in univariate and
      multivariate analyses. RESULTS: Overall, 78 women with no history of diabetes or
      GMAs were eligible for analysis. All were on stable HAART with either nevirapine
      or protease inhibitors (PIs) from at least 4 weeks at the time of sampling. GMAs
      during pregnancy were observed in 20 women (25.6%; GDM: 6, 7.7%; IGT: 14, 17.9%).
      In a multivariate analysis, after adjusting for age and ongoing antiretroviral
      treatment (PI or nevirapine), GMAs in pregnancy were significantly associated
      with HCV coinfection(adjusted odds ratio 4.16; 95% CI, 1.22-14.1;p = .022). No
      maternal or neonatalcomplications were observed. CONCLUSION: GMAs represent a
      relevant issue in the management of HIV-1-infected pregnant women. Our data
      suggest that these abnormalities are relatively common in this particular group.
      Women with HCV coinfection have an increased risk of developing GMAs during
      pregnancy and should be monitored for potential complications.

PMID- 20133272
TI  - A systematic review of the quality of trials evaluating biomedical HIV prevention
      interventions shows that many lack power.
AB  - PURPOSE: Several randomized, controlled trials (RCTs) have tested strategies to
      prevent sexual acquisition of HIV infection, but their quality has been variable.
      We aimed to identify, describe, and evaluate the quality of RCTs studying
      biomedical interventions to prevent HIV acquisition by sexual transmission.
      METHOD: We conducted a systematic review to identify all RCTs evaluating the
      efficacy of biomedical HIV prevention interventions. We assessed seven generic
      and content-specific quality components important in HIV prevention trials,
      factors influencing study power, co-interventions provided, and trial ethics.
      RESULTS: We identified 26 eligible RCTs. The median number of quality components
      judged to be in adequate or unclear was 3 (range 1-4) in 1992-1998, 3 (range 1-4)
      in 1999-2003, and 0 (range0-2) in 2004-2008 (p < .001). Common problems that may
      have biased results included low retention (median 84%), poor adherence to
      interventions requiring on going use (median < or =78%), and lower HIV incidence
      than expected a priori (in 8 of 11 trials where evaluable). CONCLUSION: Reporting
      of trials of biomedical HIV prevention interventions has improved over time.
      However, quality improvement is needed in several key areas that influence study
      power, including participant retention, adherence to interventions, and
      estimation of expected HIV incidence.

PMID- 20133273
TI  - Efficacy and safety of switching from enfuvirtide to raltegravir in patients with
      virological suppression.
AB  - OBJECTIVE: To assess the Efficacy and safety of switching from HAART containing
      enfuvirtide to raltegravir as a simplification strategy in patients with viral
      suppression and intolerance to enfuvirtide. METHODS: Thirty-six patients with
      sustained plasma HIV RNA levels <50 copies/mL for at least 3 months with
      injection site reactions and/or injection fatigue while receiving an enfuvirtide
      containing optimized background regimen switched from enfuvirtide to raltegravir
      (400 mg bid). RESULTS: Patientshad received enfuvirtide for a median of 96 weeks
      and had sustained HIV RNA <50 copies/ mL for a median of 95 weeks. One patient
      discontinued raltegravir due to the appearance of cutaneous rash (grade 2)
      unresponsive to antihistamines after 19 days of starting raltegravir. The
      remaining 35 patients were followed for 24 weeks and 18 of them for 48 weeks. All
      patients maintained virological suppression <50 copies/mL at Weeks 24 and 48. No
      patient had blips in their viral load after switching to raltegravir. There were
      no grade 3 or 4 adverse events related to raltegravir. CONCLUSIONS: A switch from
      enfuvirtide to raltegravir in virologically suppressed patients who are highly
      treatment-experienced maintained both virologic and immunologic efficacy up to 48
      weeks.

PMID- 20133274
TI  - Paraoxonase 1 R/Q alleles are associated with differential accumulation of
      saturated versus 20:5n3 fatty acid in human adipose tissue.
AB  - Serum paraoxonase 1 (PON1) function has been associated with human cardiovascular
      disease. The projected mechanism postulates interaction of PON1 with lipoproteins
      and insulin signaling resulting in alterations in lipid homeostasis. Recently,
      PON2 was shown to directly regulate triglyceride accumulation in macrophages and
      PON1 was detected in the interstitial space of adipocytes. The aims of the
      present study were a) to examine the relationship of the PON1 function with serum
      parameters related to lipid homeostasis, and b) to examine a possible role of
      PON1 in the regulation of lipid composition in the human adipose tissue. Two
      important genetic variations with functional impact on PON1 activity in humans
      are the Q192R and the L55M. The present study evaluated the impact of the Q192R
      and the L55M polymorphisms in a cross-section of the population on the island of
      Crete, as regards to PON1 activity, plasma lipids/lipoproteins, parameters of the
      metabolic syndrome, and the fatty acid composition of the adipose tissue. We
      detected a significant association of the polymorphisms with blood pressure,
      fasting blood glucose, triglycerides, apolipoprotein B, serum iron, and
      homocysteine. Furthermore, a novel function is suggested for PON1 on the fatty
      acid composition in the adipose tissue through the positive association of the R
      allele with saturated fatty acid and of the Q allele with 20:5n3 fatty acid
      deposition.

PMID- 20133279
TI  - Fragmentation and embolization of pacemaker leads as a complication of lead
      extraction.
AB  - Fragmentation and embolization of permanent pacemaker (PPM) leads into the
      pulmonary circulation is a rare complication of lead extraction procedures. We
      present two cases of lead tip embolization in patients undergoing lead
      extraction. The literature pertaining to the incidence and management of lead
      fragmentation and embolization is discussed.

PMID- 20133280
TI  - Alkylating agents in membranous nephropathy: efficacy proven beyond doubt.

PMID- 20133281
TI  - Biopsy-proven resolution of renal light-chain deposition disease after autologous
      stem cell transplantation.
AB  - Light-chain deposition disease (LCDD) is caused by an underlying clonal plasma
      cell dyscrasia in which monoclonal immunoglobulin light chains (LCs) are
      deposited in tissues, resulting in varying degrees of organ dysfunction.
      Autologous stem cell transplantation (ASCT) has been reported to stabilize renal
      function in patients with LCDD, but currently, no evidence of histopathologic
      resolution of LC deposition after ASCT exists. We present a patient, with severe
      renal dysfunction due to LCDD, who was treated with high-dose melphalan and ASCT
      that resulted in a significant and extended period of improved renal function.
      Four years after the initial improvement, the patient developed nephrotic range
      proteinuria, without any evidence of relapse of the plasma cell dyscrasia. At
      that time, a repeat renal biopsy showed complete resolution of LC depositions and
      development of extensive glomerulosclerosis, thus explaining proteinuria. To the
      best of our knowledge, this is the first report of a biopsy-proven resolution of
      renal LCDD following ASCT. A timely application of ASCT should be considered in
      LCDD to prevent deterioration of renal function in the long run.

PMID- 20133282
TI  - Systems biology to battle vascular disease.

PMID- 20133283
TI  - Half the dosage, similar efficacy, less bleeding: the new tissue plasminogen
      activator regimen for pulmonary embolism?

PMID- 20133284
TI  - Pulmonary rehabilitation for restrictive lung diseases.

PMID- 20133285
TI  - Life and death decisions in the middle of the night: teaching the assessment of
      decision-making capacity.

PMID- 20133286
TI  - Changing culture: a new view of human error and patient safety.

PMID- 20133288
TI  - CURVES: a mnemonic for determining medical decision-making capacity and providing
      emergency treatment in the acute setting.
AB  - The evaluation of medical decision-making capacity and provision of emergency
      treatment in the acute care setting may present a significant challenge for both
      physicians-in-training and attending physicians. Although absolutely essential to
      the proper care of patients, recalling criteria for decision-making capacity may
      prove cumbersome during a medical emergency. Likewise, the requirements for
      providing emergency treatment must be fulfilled. This article presents a mnemonic
      (CURVES: Choose and Communicate, Understand, Reason, Value, Emergency, Surrogate)
      that addresses the abilities a patient must possess in order to have decision
      making capacity, as well as the essentials of emergency treatment. It may be used
      in conjunction with, or in place of, lengthier capacity-assessment tools,
      particularly when time is of the essence. In addition, the proposed tool assists
      the practitioner in deciding whether emergency treatment may be administered, and
      in documenting medical decisions made during an acute event.

PMID- 20133289
TI  - Smoking cessation.
AB  - Cigarette smoking is arguably the major cause of preventable morbidity and
      mortality in the developed world. The Department of Health and Human Services in
      the United States classifies cigarette smoking as a chronic, often relapsing
      disease. Like most complex diseases, genetic and environmental factors play
      important roles and contribute to both smoking initiation and persistence. This
      review summarizes pharmacologic and nonpharmacologic interventions for smoking
      cessation and provides references to evidence-based guidelines and support
      material. As smoking is an etiologic and exacerbating factor for lung diseases,
      the pulmonary physician should be particularly expert in smoking cessation
      interventions.

PMID- 20133290
TI  - Classification of the thoroughness of mediastinal staging of lung cancer.
AB  - There are many complementary techniques for mediastinal staging of lung cancer.
      It is increasingly apparent that the accuracy of mediastinal staging depends not
      only on which test is used but also on technical factors of how the procedure is
      performed. This article reviews data regarding such technical factors and
      proposes a classification schema of the thoroughness of execution of mediastinal
      staging tests. Such a schema is needed for a thoughtful discussion of how
      mediastinal staging tests should be integrated and for the development of
      standards of good quality care for patients with non-small cell lung cancer.

PMID- 20133291
TI  - Preoperative briefing in the operating room: shared cognition, teamwork, and
      patient safety.
AB  - Contemporary preoperative team briefings conducted to improve patient safety
      focus mainly on supplying identification details regarding the patient and the
      surgical procedure. Drawing on cognitive theory principles, in this study a
      briefing protocol was developed that presents a broader perspective model of the
      patient and the planned procedure. In addition to customary identification
      details and drug sensitivities, the new briefing also includes review of
      significant background information, needed equipment, planned surgery stages, and
      so forth. The briefing content was developed following 130 continuous,
      nonstructured observations conducted in gynecologic and orthopedic operating
      rooms. The briefing form was designed as a large poster hung in a visible
      position on the operating room wall. The poster guides the team members (ie,
      nurses, surgeons, and anesthesiologists) in their conduct. Briefing is conducted
      orally, and no written records are required. The number of nonroutine events (ie,
      situations that, if not corrected, might lead to patient harm) observed in the
      130 surgeries conducted without briefing was compared with the number of events
      in 102 surgeries in which briefing was conducted. There was a 25% reduction in
      the number of nonroutine events when briefing was conducted and a significant
      increase in the number of surgeries in which no nonroutine event was observed.
      Team members evaluated the briefing as most valuable for their own work, the
      teamwork, and patient safety. Following the study, the new briefing format was
      accepted and adopted for routine use. Team briefings designed to supply a broader
      perspective surgery model may be an easy-to-apply tool to reduce the number of
      nonroutine events during surgery and increase patient safety.

PMID- 20133292
TI  - Vaginal involvement in a patient with sarcoidosis.
AB  - We report the case of a woman who presented with vaginal symptoms and was proven
      to have biopsy-confirmed sarcoidosis of the vaginal wall. To our knowledge, this
      is the first reported case of this entity. An additional unusual finding was that
      her symptoms of gynecologic sarcoidosis occurred at the time of initial
      presentation of her pulmonary sarcoidosis.

PMID- 20133293
TI  - Diffuse alveolar hemorrhage induced by everolimus.
AB  - Pulmonary toxicity is a known complication of the proliferation signal inhibitor
      (PSI) sirolimus and consists of diverse entities such as interstitial
      pneumonitis, lymphocytic alveolitis, bronchiolitis obliterans with organizing
      pneumonia, and diffuse alveolar hemorrhage. Several cases of interstitial
      pneumonitis have also been reported with the more recently developed PSI
      everolimus. In this report, a case of diffuse alveolar hemorrhage attributed to
      everolimus is described. The patient presented with respiratory symptoms of
      insidious onset, ultimately resulting in severe respiratory failure characterized
      by high lactate dehydrogenase levels, patchy ground-glass infiltrates, and bloody
      BAL fluid with predominance of iron-loaded macrophages and monocytes. Withdrawal
      of the offending drug and temporary association of high-dose steroids resulted in
      a rapid recovery. Given that prompt drug discontinuation is potentially life
      saving, PSI-induced pulmonary toxicity should be considered in the differential
      diagnosis of patients treated with PSIs and presenting with respiratory symptoms
      or pulmonary lesions.

PMID- 20133294
TI  - An elderly woman with chronic dyspnea and endobronchial lesion.

PMID- 20133295
TI  - Diagnostic utility and clinical application of imaging for pleural space
      infections.
AB  - Timely diagnosis of pleural space infections and rapid initiation of effective
      pleural drainage for those patients with complicated parapneumonic effusions or
      empyema represent keystone principles for managing patients with pneumonia.
      Advances in chest imaging provide opportunities to detect parapneumonic effusions
      with high sensitivity in patients hospitalized for pneumonia and to guide
      interventional therapy. Standard radiographs retain their primary role for
      screening patients with pneumonia for the presence of an effusion to determine
      the need for thoracentesis. Ultrasonography and CT scanning, however, have
      greater sensitivity for fluid detection and provide additional information for
      determining the extent and nature of pleural infection. MRI and PET scan can
      image pleural disease, but their role in managing parapneumonic effusions is not
      yet clearly defined. Effective application of chest images for patients at risk
      for pleural infection, however, requires a comprehensive understanding of the
      unique features of each modality and relative value. This review presents the
      diagnostic usefulness and clinical application of chest imaging studies for
      evaluating and managing pleural space infections in patients hospitalized for
      pneumonia.

PMID- 20133296
TI  - Spontaneous hemothorax and recurrent hemoptysis in a 26-year-old man with skin
      lesions.

PMID- 20133297
TI  - A young woman with pulmonary hemorrhage and hypoxic respiratory failure.

PMID- 20133298
TI  - Translating patient education materials.

PMID- 20133303
TI  - Metabolic syndrome and impaired lung function.

PMID- 20133304
TI  - Vitamin D and mortality from pulmonary fibrosis.

PMID- 20133305
TI  - Postobstructive pulmonary edema after chronic airway obstruction relief: a
      positive end-expiratory pressure effect.

PMID- 20133306
TI  - The effect of continuous positive airway pressure on C-reactive protein levels in
      patients with obstructive sleep apnea syndrome.

PMID- 20133307
TI  - The effect of specific allergen inhalation on adipokine level: can adiponectin
      oligomers and hormones be a factor?

PMID- 20133308
TI  - Assess dental plaque and suction-extricated bacteria adequately.

PMID- 20133309
TI  - Echocardiography in hemodynamic monitoring.

PMID- 20133310
TI  - A comparative study of two different metered-dose inhaler-valved holding chambers
      in the administration of salbutamol.

PMID- 20133311
TI  - The role of aldosterone in pulmonary venous hypertension.

PMID- 20133312
TI  - New disease--new terminology.

PMID- 20133320
TI  - At-home palliative sedation for end-of-life cancer patients.
AB  - Using a decision-making and treatment checklist developed to facilitate the at
      home palliative sedation process, we assessed the incidence and efficacy of
      palliative sedation for end-of-life cancer patients with intractable symptoms who
      died at home. We retrospectively reviewed the medical records of 370 patients who
      were followed by a palliative home care team. Twenty-nine of 245 patients (12%)
      who died at home had received palliative sedation. The mean age of the patients
      who received palliative sedation was 58 +/- 17 years, and the mean age of the
      patients who did not receive palliative sedation was 69 +/- 15 years (p = 0.002).
      No other differences were detected between patients who did or did not receive
      palliative sedation. The most common indications for palliative sedation were
      delirium (62%) and dyspnea (14%). Twenty-seven patients (93%) received midazolam
      for palliative sedation (final mean dose of 74 mg), and two (7%) received
      levomepromazine (final mean dose of 125 mg). The mean time between palliative
      sedation initiation and time of death was 2.6 days. In 13 of the cases (45%), the
      palliative sedation decision was made with the patient and his or her family
      members, and in another 13 patients (45%), the palliative sedation decision was
      made only with the patient's family members. We concluded that palliative
      sedation may be used safely and efficaciously to treat dying cancer patients with
      refractory symptoms at home.

PMID- 20133321
TI  - Medicalisation: the role of e-pharmacies in iatrogenic harm.

PMID- 20133322
TI  - Parental occupation and risk of small-for-gestational-age births: a nationwide
      epidemiological study in Sweden.
AB  - BACKGROUND: Although evidence suggests that some occupations may be a risk factor
      for small-for-gestational age (SGA) birth, associations between a wide range of
      maternal and paternal occupations and risk of SGA births remain unclear. Our
      objective was to analyze the risk of SGA births by parental occupation, including
      the entire Swedish population of mothers (> or =20 years) and fathers. METHODS:
      We linked nationwide data (1990-2004) on singletons born to employed mothers to
      nationwide data on maternal and paternal occupation and other individual-level
      variables. Information on parental occupations was obtained from the 1990 census.
      Approximately 95% of SGA births (calculated using normative data) were defined on
      the basis of ultrasound. Odds ratios of SGA birth were calculated with 95%
      confidence intervals. Women and men were analyzed separately. RESULTS: There were
      816,310 first singleton live births during the study period, of which 29,603 were
      SGA events. Families with low incomes had an increased risk of SGA births. After
      accounting for maternal age at the infant's birth, period of birth, family
      income, region of residence, marital status and smoking habits, several maternal
      occupational groups (including 'mechanics and iron and metalware workers' and
      'packers, loaders and warehouse workers') had a significantly higher risk of SGA
      birth than the reference group (all women in the study population). Among
      paternal occupational groups, only waiters had an increased risk of SGA birth.
      CONCLUSIONS: This large-scale follow-up study shows that maternal occupation
      affects risk of SGA birth, whereas paternal occupation does not seem to have an
      impact on SGA birth. Further studies are required to examine the specific agents
      in those maternal occupations that are associated with an increased risk of SGA
      birth.

PMID- 20133323
TI  - The effects of metformin and letrozole on endometriosis and comparison of the two
      treatment agents in a rat model.
AB  - BACKGROUND: Our aim was to investigate the effects of metformin and letrozole on
      experimentally induced endometriosis in a rat model. METHODS: Endometriotic
      implants were surgically formed, and 38 rats were randomly divided into four
      groups. Group 1 (control group, 8 rats) was given no medication. Group 2
      (metformin group, 10 rats) was given 100 mg/kg/day of oral metformin. Group 3
      (metformin group, 10 rats) was given 200 mg/kg/day of oral metformin. Group 4
      (letrozole group, 10 rats) was given 0.1 mg/kg/day of oral letrozole. All rats
      continued to receive the treatment for 4 weeks and then were sacrificed to assess
      the size of implants and scores of adhesions. The histopathologic scores of
      implants in excised endometriotic foci were examined by a pathologist. RESULTS:
      The mean surface area of endometriotic implants was similar in all groups before
      the treatment. Although the area was not reduced in controls, it was found to be
      significantly reduced in all treatment groups (44.50 +/- 23.37, 5.90 +/- 2.37,
      4.30 +/- 1.33, 6.90 +/- 3.72 mm(2), respectively; P < 0.05). The effect was
      comparable between the treatment groups. The histopathologic assessment revealed
      that the histopathologic score of implants was lowest after 100 mg/kg/day
      metformin. Additionally, metformin reduced the severity of adhesions.
      CONCLUSIONS: Metformin and letrozole caused a statistically significant
      regression of endometriotic implants. The effects of metformin on endometriotic
      tissue were at least comparable to letrozole.

PMID- 20133324
TI  - Platelet-rich plasma: any substance into it?

PMID- 20133325
TI  - Are we facing a new paradigm of inactivity physiology?

PMID- 20133326
TI  - Breastfeeding, the use of docosahexaenoic acid-fortified formulas in infancy and
      neuropsychological function in childhood.
AB  - OBJECTIVE: To investigate the relation between breastfeeding, use of
      docosahexaenoic acid (DHA)-fortified formula and neuropsychological function in
      children. DESIGN: Prospective cohort study. SETTING: Southampton, UK. SUBJECTS:
      241 children aged 4 years followed up from birth. MAIN OUTCOME MEASURES: IQ
      measured by the Wechsler Pre-School and Primary Scale of Intelligence (3rd edn),
      visual attention, visuomotor precision, sentence repetition and verbal fluency
      measured by the NEPSY, and visual form-constancy measured by the Test of Visual
      Perceptual Skills (Non-Motor). RESULTS: In unadjusted analyses, children for whom
      breast milk or DHA-fortified formula was the main method of feeding throughout
      the first 6 months of life had higher mean full-scale and verbal IQ scores at age
      4 years than those fed mainly unfortified formula. After adjustment for potential
      confounding factors, particularly maternal IQ and educational attainment, the
      differences in IQ between children in the breast milk and unfortified formula
      groups were severely attenuated, but children who were fed DHA-fortified formula
      had full-scale and verbal IQ scores that were respectively 5.62 (0.98 to 10.2)
      and 7.02 (1.56 to 12.4) points higher than children fed unfortified formula.
      However, estimated total intake of DHA in milk up to age 6 months was not
      associated with subsequent IQ or with score on any other test. CONCLUSIONS:
      Differences in children's intelligence according to type of milk fed in infancy
      may be due more to confounding by maternal or family characteristics than to the
      amount of long-chain polyunsaturated fatty acids they receive in milk.

PMID- 20133327
TI  - The incidence and nature of prescribing and medication administration errors in
      paediatric inpatients.
AB  - OBJECTIVES: To determine the incidence and nature of prescribing and medication
      administration errors in paediatric inpatients. DESIGN: Prospective review of
      drug charts to identify prescribing errors and prospective observation of nurses
      preparing and administering drugs to identify medication administration errors.
      In addition, incident reports were collected for each ward studied. PARTICIPANTS:
      Paediatric patients admitted to hospitals and nurses administering medications to
      these patients. SETTING: 11 wards (prescribing errors) and 10 wards (medication
      administration errors) across five hospitals (one specialist children's teaching
      hospital, one nonteaching hospital and three teaching hospitals) in the London
      area (UK). MAIN OUTCOME MEASURES: Number, types and incidence of prescribing and
      medication administration errors, using practitioner-based definitions. RESULTS:
      391 prescribing errors were identified, giving an overall prescribing error rate
      of 13.2% of medication orders (95% CI 12.0 to 14.5). There was great variation in
      prescribing error rates between wards. Incomplete prescriptions were the most
      common type of prescribing error, and dosing errors the third most common. 429
      medication administration errors were identified; giving an overall incidence of
      19.1% (95% CI 17.5% to 20.7%) erroneous administrations. Errors in drug
      preparation were the most common, followed by incorrect rates of intravenous
      administration. CONCLUSIONS: Prescribing and medication administration errors are
      not uncommon in paediatrics, partly as a result of the extra challenges in
      prescribing and administering medication to this patient group. The causes and
      extent of these errors need to be explored locally and improvement strategies
      pursued.

PMID- 20133328
TI  - Stress and psychosomatic symptoms in Chinese school children: cross-sectional
      survey.
AB  - OBJECTIVE: The Chinese educational system is highly competitive from the start of
      primary school with great emphasis on academic performance and intolerance of
      failure. This study aimed to explore the pressures on primary schoolchildren, and
      to determine the relationship between these pressures and psychosomatic symptoms:
      abdominal pain and headache. DESIGN: Cross-sectional survey using self-completion
      questionnaires. SETTING/PARTICIPANTS: 9- to 12-year-olds in primary schools in
      urban and rural areas of Zhejiang Province, eastern China. OUTCOME MEASURES:
      Proportion of children with defined school-related stressors and frequency of
      psychosomatic illness. RESULTS: Completed questionnaires were obtained from 2191
      children. All stressors were common in boys and girls and in urban and rural
      schools. Eighty-one per cent worry 'a lot' about exams, 63% are afraid of the
      punishment of teachers, 44% had been physically bullied at least sometimes, with
      boys more often victims of bullying, and 73% of children are physically punished
      by parents. Over one-third of children reported psychosomatic symptoms at least
      once per week, 37% headache and 36% abdominal pain. All individual stressors were
      highly significantly associated with psychosomatic symptoms. Children identified
      as highly stressed (in the highest quartile of the stress score) were four times
      as likely to have psychosomatic symptoms. CONCLUSIONS: The competitive and
      punitive educational environment leads to high levels of stress and psychosomatic
      symptoms in Chinese primary schoolchildren. Measures to reduce unnecessary stress
      on children in schools should be introduced urgently.

PMID- 20133329
TI  - A phantom study of nodule size evaluation with chest tomosynthesis and computed
      tomography.
AB  - The aim of the present study was to investigate nodule size measurements with
      chest tomosynthesis (TS) and computed tomography (CT). A 26-mm thick phantom,
      composed of a Polylite block with embedded spheres of different materials and
      sizes (4-20 mm), was scanned by both CT and TS. Six observers without prior
      knowledge of the true diameters of the spheres independently measured the
      diameter of the spheres on the CT and TS images. Four observers were allowed to
      change the window settings and two of the observers used predetermined fixed
      viewing conditions. The mean relative errors for all observers and all measured
      spheres compared with the known diameter of the spheres were 1.4 % (standard
      deviation, SD: 5.4 %) on CT images and -1.1 % (SD: 5.0 %) on TS images. With
      regard to the four observers where the window settings were at the discretion of
      the observer, the mean relative errors were 1.4 % (SD: 6.4 %) on CT images and 
      1.7 % (SD: 5.7 %) on TS images. Regarding the two observers using identical
      viewing conditions the mean relative error was 1.5 % (SD: 2.8 %) on CT images and
      0.2 % (SD: 2.6 %) on TS images. In conclusion, the study suggests that nodule
      size measurements on chest TS might be an alternative to measurements on CT.

PMID- 20133330
TI  - Shielding design of a brachytherapy unit at the Korle Bu teaching hospital in
      Ghana: comparison of theoretical calculations and experimental study.
AB  - A theoretical study was carried out to re-evaluate the integrity of the
      biological shielding of (137)Cs brachytherapy unit at the Korle Bu Teaching
      Hospital, Ghana, and the results were verified by measurement of the dose rates
      at selected locations. The primary objective was to determine the current state
      of protection and safety of staff and the general public. Shielding design of the
      brachytherapy unit at the hospital was based on postulated workload and occupancy
      factors of the facility. The facility has been in existence for 12 y and has
      accumulated operational workload data that differs from the postulated one. The
      results show that despite the variation in actual and postulated workloads, the
      dose rates were below the reference values 0.5 microSv h(-1) for public areas and
      7.5 microSv h(-1) for controlled areas. These values were in the range of 0.10
      0.12 microSv h(-1) for public areas and of 0.50-2.10 microSv h(-1) for controlled
      areas.

PMID- 20133331
TI  - Positioned and G/C-capped poly(dA:dT) tracts associate with the centers of
      nucleosome-free regions in yeast promoters.
AB  - Eukaryotic transcriptional regulation is mediated by the organization of
      nucleosomes in promoter regions. Most Saccharomyces cerevisiae promoters have a
      highly stereotyped chromatin organization, where nucleosome-free regions (NFR)
      are flanked by well-ordered nucleosomes. We have found that yeast promoters fall
      into two classes differing in NFR sharpness, and that this distinction follows a
      known transcriptional dichotomy in yeast genes. A class of yeast promoters having
      well-defined NFRs are characterized by positioned patterns of poly(dA:dT) tracts
      with several novel features. First, poly(dA:dT) tracts are localized in a strand
      dependent manner, with poly(dA) tracts lying proximal to transcriptional start
      sites and poly(dT) tracts lying distal, and collectively define a symmetry axis
      that is coincident with NFR centers. Second, poly(dA:dT) tracts are
      preferentially "capped" by G:C residues on the terminus proximal to the symmetry
      axis. Both signature features co-vary with fine positional variations between
      NFRs, establishing a closely knit relationship between poly(dA:dT) tracts, their
      capping patterns, and the central coordinates of NFRs. We found that these
      features are unique to promoters with well-defined NFRs, and that these promoters
      display significant difference between in vitro and in vivo nucleosome occupancy
      patterns. These observations are consistent with a model in which localized and
      G:C-capped poly(dA:dT) tracts initiate or facilitate the formation of NFRs at
      their center, possibly with chromatin remodeling and transcriptional machines
      involved.

PMID- 20133332
TI  - Digital transcriptome profiling from attomole-level RNA samples.
AB  - Accurate profiling of minute quantities of RNA in a global manner can enable key
      advances in many scientific and clinical disciplines. Here, we present low
      quantity RNA sequencing (LQ-RNAseq), a high-throughput sequencing-based technique
      allowing whole transcriptome surveys from subnanogram RNA quantities in an
      amplification/ligation-free manner. LQ-RNAseq involves first-strand cDNA
      synthesis from RNA templates, followed by 3' polyA tailing of the single-stranded
      cDNA products and direct single molecule sequencing. We applied LQ-RNAseq to
      profile S. cerevisiae polyA+ transcripts, demonstrate the reproducibility of the
      approach across different sample preparations and independent instrument runs,
      and establish the absolute quantitative power of this method through comparisons
      with other reported transcript profiling techniques and through utilization of
      RNA spike-in experiments. We demonstrate the practical application of this
      approach to define the transcriptional landscape of mouse embryonic and induced
      pluripotent stem cells, observing transcriptional differences, including over 100
      genes exhibiting differential expression between these otherwise very similar
      stem cell populations. This amplification-independent technology, which utilizes
      small quantities of nucleic acid and provides quantitative measurements of
      cellular transcripts, enables global gene expression measurements from minute
      amounts of materials and offers broad utility in both basic research and
      translational biology for characterization of rare cells.

PMID- 20133333
TI  - Dynamic changes in the human methylome during differentiation.
AB  - DNA methylation is a critical epigenetic regulator in mammalian development.
      Here, we present a whole-genome comparative view of DNA methylation using
      bisulfite sequencing of three cultured cell types representing progressive stages
      of differentiation: human embryonic stem cells (hESCs), a fibroblastic
      differentiated derivative of the hESCs, and neonatal fibroblasts. As a reference,
      we compared our maps with a methylome map of a fully differentiated adult cell
      type, mature peripheral blood mononuclear cells (monocytes). We observed many
      notable common and cell-type-specific features among all cell types. Promoter
      hypomethylation (both CG and CA) and higher levels of gene body methylation were
      positively correlated with transcription in all cell types. Exons were more
      highly methylated than introns, and sharp transitions of methylation occurred at
      exon-intron boundaries, suggesting a role for differential methylation in
      transcript splicing. Developmental stage was reflected in both the level of
      global methylation and extent of non-CpG methylation, with hESC highest,
      fibroblasts intermediate, and monocytes lowest. Differentiation-associated
      differential methylation profiles were observed for developmentally regulated
      genes, including the HOX clusters, other homeobox transcription factors, and
      pluripotence-associated genes such as POU5F1, TCF3, and KLF4. Our results
      highlight the value of high-resolution methylation maps, in conjunction with
      other systems-level analyses, for investigation of previously undetectable
      developmental regulatory mechanisms.

PMID- 20133334
TI  - A consensus-based guideline defining the clinical target volume for pelvic lymph
      nodes in external beam radiotherapy for uterine cervical cancer.
AB  - OBJECTIVE: To develop a consensus-based guideline as well as an atlas defining
      pelvic nodal clinical target volumes in external beam radiotherapy for uterine
      cervical cancer. METHODS: A working subgroup to establish the consensus-based
      guideline on clinical target volumes for uterine cervical cancer was formulated
      by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July
      2008. The working subgroup consisted of seven radiation oncologists. The process
      resulting in the consensus included a comparison of contouring on CT images among
      the members, reviewing of published textbooks and the relevant literature and a
      distribution analysis of metastatic nodes on computed tomography/magnetic
      resonance imaging of actual patients. RESULTS: The working subgroup defined the
      pelvic nodal clinical target volumes for cervical cancer and developed an
      associated atlas. As a basic criterion, the lymph node clinical target volume was
      defined as the area encompassed by a 7 mm margin around the applicable pelvic
      vessels. Modifications were made in each nodal area to cover adjacent adipose
      tissues at risk of microscopic nodal metastases. Although the bones and muscles
      were excluded, the bowel was not routinely excluded in the definition. Each of
      the following pelvic node regions was defined: common iliac, external iliac,
      internal iliac, obturator and presacral. Anatomical structures bordering each
      lymph node region were defined for six directions; anterior, posterior, lateral,
      medial, cranial and caudal. Drafts of the definition and the atlas were reviewed
      by members of the JCOG Gynecologic Cancer Study Group (GCSG). CONCLUSIONS: We
      developed a consensus-based guideline defining the pelvic node clinical target
      volumes that included an atlas. The guideline will be continuously updated to
      reflect the ongoing changes in the field.

PMID- 20133335
TI  - Phase I and pharmacokinetic study of ABI-007, albumin-bound paclitaxel,
      administered every 3 weeks in Japanese patients with solid tumors.
AB  - OBJECTIVE: ABI-007 is a novel Cremophor EL-free nanoparticle albumin-bound
      paclitaxel. This Phase I study was designed to evaluate tolerability and
      determine recommended dose for Japanese patients when ABI-007 was administered in
      every-3-week schedule. Pharmacokinetics of paclitaxel was also assessed. METHODS:
      Patients with advanced solid tumors refractory to standard therapy received a 30
      min intravenous infusion of ABI-007 every 3 weeks without pre-medications at 200,
      260 or 300 mg/m(2), respectively. Tolerability and recommended dose were
      determined by the standard '3 + 3' rule. RESULTS: No dose-limiting toxicity was
      observed, despite the dose escalation. In another cohort, 260 mg/m(2) was re
      evaluated and resulted in no dose-limiting toxicity. Grade 3 or 4 neutropenia was
      reported for the majority of patients (n = 8) but no incidence of febrile
      neutropenia. Non-hematological toxicities were generally mild except for Grade 3
      sensory neuropathy (n = 3). Pharmacokinetic study demonstrated the area under the
      curve of paclitaxel increased with increasing the dosage, and comparable
      pharmacokinetic parameters to the western population. Partial response was
      observed in three non-small cell lung cancer patients. Two of whom had received
      docetaxel-containing chemotherapy prior to the study. CONCLUSIONS: ABI-007
      administered in every-3-week schedule was well tolerated up to 300 mg/m(2), and
      recommended dose was determined at 260 mg/m(2) in consideration of efficacy,
      toxicities and similarity of pharmacokinetic profile in western studies.
      Additional studies of single-agent ABI-007 as well as platinum-based
      combinations, particularly in patients with non-small cell lung cancer, are
      warranted.

PMID- 20133336
TI  - Usefulness of narrow-band imaging for detecting the primary tumor site in
      patients with primary unknown cervical lymph node metastasis.
AB  - OBJECTIVE: We sometimes experienced patients with primary unknown cervical lymph
      node metastasis. In such cases, if computed tomography, magnetic resonance
      imaging, laryngoscopy and gastrointestinal endoscopy cannot detect a primary
      site, there is no other effective method to identify a possible primary tumor. We
      investigated whether narrow-band imaging can detect a possible primary tumor in
      such. METHODS: Forty-six patients with primary unknown cervical lymph node
      metastasis were surveyed about primary tumors, from January 2003 to December
      2006. All cervical lymph nodes were histologically proved to be squamous cell
      carcinoma by fine-needle aspiration cytology. Narrow-band imaging combined with
      magnifying endoscopy was used to identify the primary site in the head and neck
      region and cervical esophagus. Histological analysis was performed for all
      suspicious lesions by a biopsy specimen. RESULTS: Twenty-six lesions were
      suspected to be cancerous lesions by narrow-band imaging in the head and neck
      region. Sixteen lesions in 16 (35%, 16/46) patients were squamous cell carcinoma.
      Ten lesions were located in the hypopharynx and the remaining six lesions were
      located in the oropharynx. White light endoscopy could not point out any lesion.
      CONCLUSIONS: Narrow-band imaging endoscopy can detect possible primary cancer in
      patients with primary unknown cervical lymph node metastasis.

PMID- 20133337
TI  - Human papillomavirus DNA in plasma of patients with HPV16 DNA-positive uterine
      cervical cancer.
AB  - OBJECTIVES: The squamous cell carcinoma antigen is considered the most accurate
      serologic tumor marker for uterine cervical carcinoma. However, serum squamous
      cell carcinoma antigen levels were found to correlate significantly with clinical
      severity of atopic dermatitis and chronic renal failure. The present study was
      conducted in patients with human papillomavirus 16 DNA-positive uterine cervical
      cancer to determine the plasma level of human papillomavirus 16 DNA and the
      diagnostic values of plasma human papillomavirus DNA in these patients. METHODS:
      Forty-three human papillomavirus 16-positive patients with cervical
      intraepithelial neoplasia or uterine cervical squamous cell carcinoma were
      recruited in this study. The diagnosis was cervical cancer in 20 patients, high
      grade squamous intraepithelial lesions in 21, low-grade squamous intraepithelial
      lesions in 1 and negative for intraepithelial lesion or malignancy in 3 patients.
      Before any treatment, blood samples were collected from all patients. For
      analysis of human papillomavirus DNA in plasma of patients with cervical cancer,
      quantitative polymerase chain reaction fluorescent assay for human papillomavirus
      16 was performed using human papillomavirus 16 primers and SYBR Green dye using
      the LightCycler 480 SW1.5 apparatus. RESULTS: Plasma human papillomavirus 16 DNA
      was detected in only 30.0% of the patients with human papillomavirus 16-positive
      cervical cancer and in none of normal controls. The copy number of plasma human
      papillomavirus 16 DNA was higher in patients with invasive cancer than in those
      with cervical intraepithelial neoplasia (CIN3), micro-invasive cancer and in
      normal individuals. CONCLUSIONS: These results indicated that the plasma human
      papillomavirus DNA level could be potentially used as a marker of low-invasive
      cervical cancer tumors in patients with normal squamous cell carcinoma antigen
      levels before treatment.

PMID- 20133338
TI  - Detection of DNA strand breaks by comet assay in sputum leucocytes of bitumen
      exposed workers: a pilot study.
AB  - DNA strand breaks were determined in leucocytes of induced sputum (IS) and
      compared with DNA strand breaks in blood lymphocytes from 42 bitumen-exposed
      workers pre and post shift. Comet assay results were expressed in arbitrary units
      based on visual scoring (sputum leucocytes) and Olive tail moment (OTM, blood
      lymphocytes). DNA damage in IS leucocytes was overall high but did not change
      during shift. Level of DNA strand breaks in IS samples correlated with total cell
      count and neutrophil content (Spearman rank correlation coefficient r(s) = 0.47,
      p = 0.001, r(s)= 0.48, p = 0.001, respectively) and with IL-8 concentration
      before and after shift (r(s) = 0.31, P = 0.048, and r(s) = 0.43, P = 0.005). DNA
      damage in IS was not associated with DNA strand breaks in blood lymphocytes (r(s)
      = -0.04, p = 0.802 before shift, r(s) = 0.27, p = 0.088 after shift). A higher
      level of DNA strand breaks was measured in blood lymphocytes before shift (median
      OTM 1.7 before and 1.3 after shift, p = 0.023). A strong correlation was found
      between the number of neutrophils and IL-8 concentration in IS before and after
      shift (r(s) = 0.77 and r(s)= 0.75, p < 0.001). This study showed an association
      between genotoxic and inflammatory effects in the lower airways and compared
      simultaneously DNA strand breaks in IS and blood of bitumen-exposed workers.

PMID- 20133339
TI  - Case report: hip septic arthritis and abcess after diagnostic coronary
      angiography.
AB  - Coronary angiography is an invasive procedure which can have some complications.
      Septic arthritis and abscess after coronary angiography are extremely rare. In
      this case, a 49-year-old-man presented to our hospital with non-ST-segment
      elevation myocardial infarction. After coronary angiography, he had right leg
      weakness, femoral palsy, inguinal pain, but there was no bleeding or hematoma.
      The cause was right hip septic arthritis and abscess.

PMID- 20133340
TI  - Data on education: from population statistics to epidemiological research.
AB  - BACKGROUND: Level of education is in many fields of research used as an indicator
      of social status. METHODS: Using Statistics Denmark's register for education and
      employment of the population, we examined highest completed education with a
      birth-cohort perspective focusing on people born between 1930 and 1974. RESULTS:
      Irregularities in the educational data were found for both men and women born
      from 1951 to 1957. For the birth cohorts born from 1951 to 1954, a sudden
      increase in the proportion of persons with basic school education only was seen,
      and a following decrease in this proportion was seen for the birth cohorts born
      from 1955 to 1957. For the same birth cohorts, a reverse curve was found for the
      proportion with vocational training as highest completed education. Using
      proportion of women with at least one child at the age of 30, our analysis
      illustrated that spurious patterns may emerge when other social phenomena are
      analysed by partly misclassified educational groups. CONCLUSIONS: Our findings
      showed that register data are not always to be taken at face value and that
      thorough analysis may unravel unexpected irregularities. Although such data
      errors may be remedied in analyses of population trends by use of extrapolated
      values, solutions are less obvious in epidemiological research using individual
      level data.

PMID- 20133341
TI  - Peripheral arterial disease, chronic kidney disease, and mortality: the Chinese
      Ankle Brachial Index Cohort Study.
AB  - The purpose of this study was to investigate the association between chronic
      kidney disease (CKD) and peripheral arterial disease (PAD) and examine the
      combined effect of CKD and PAD on all-cause and cardiovascular disease (CVD)
      mortality. The Chinese Ankle Brachial Index Cohort consisted of 3732 adults aged
      35 years or older enrolled in 2004 and followed-up in 2007. Complete baseline
      data were compiled on 3610 people which were examined in the final analysis.
      Mortality surveillance was completed from December 2007 to February 2008.
      Survival analysis was used to compare the survival rate in different CKD/PAD
      groups. The relative risks (RR) of death from all-cause and CVD were compared
      using a Cox regression model. It was found that the prevalence of PAD in patients
      with and without CKD was 41.9% and 22.3%, respectively (p < 0.001). The survival
      rate for the CKD and PAD group was significantly lower than that for any single
      disease, for both all-cause and CVD mortality (log-rank: p < 0.001). In
      conclusion, CKD is a risk factor for PAD. The combined CKD and PAD patients had
      the highest risk for all-cause and CVD mortality. Early recognition of risk can
      be made by taking an ankle-brachial index measurement of PAD; a corresponding
      laboratory assessment should be used as a measurement of renal function for PAD
      patients.

PMID- 20133342
TI  - Common polymorphisms of Fibulin-5 and the risk of abdominal aortic aneurysm
      development.
AB  - Fibulin-5 is a crucial protein in the connective tissue structure of the aortic
      wall. The purpose of this study was to determine if genetic variation within the
      Fibulin-5 gene was associated with abdominal aortic aneurysms (AAA). AAA
      patients, with disease-free controls, were recruited and a past medical history
      questionnaire completed. Three single nucleotide polymorphisms (SNPs) in the
      FBLN5 gene (rs2498834, rs2430366 and rs2254320) were genotyped. The two cohorts
      were compared and haplotype analysis performed. A total of 230 AAA cases and 278
      controls were successfully genotyped. The mean age was 71.9 years (+/- 6.8). No
      difference between cases and controls was found in the distribution of alleles of
      FBLN5 SNPs rs2498834 (p = 0.47), rs2430366 (p = 0.45) or rs2254320 (p = 0.46).
      Haplotype analysis did not reveal any significant difference. In conclusion,
      genetic variation within FBLN5 is unlikely to play any role in the development of
      AAA.

PMID- 20133343
TI  - Ankle-brachial index performance among internal medicine residents.
AB  - The ankle-brachial index (ABI) is the standard test used in clinical practice to
      detect peripheral artery disease (PAD) and is a powerful predictor of adverse
      cardiovascular outcomes. This study sought to measure the baseline knowledge of
      the ABI test among a sample of internal medicine residents and to examine the
      impact of an educational intervention on performance of the test. A total of 29
      residents were asked to perform three tasks, with the performance of each task
      being assessed using a point-based scoring system: measure an ABI on a normal
      volunteer (15 points), calculate the ABI based on data from a hypothetical
      patient (3 points), and interpret a range of ABI values (6 points). A
      standardized educational intervention was then provided and post-education
      performance was assessed for each task using the same scoring system. At
      baseline, 4% of residents correctly measured the ABI, 10% correctly calculated
      the ABI, and 45% correctly interpreted the ABI. Baseline performance was
      unaffected by year of residency training. Following the educational intervention,
      50% of residents correctly measured the ABI, 75% correctly calculated the ABI,
      and 88% correctly interpreted the ABI. The mean score for the tasks of ABI
      measurement, calculation and interpretation between baseline and post-education
      were 4.6 +/- 3 and 13.9 +/- 1.6 (p < 0.0001), 1 +/- 0.9 and 2.3 +/- 1.2 (p =
      0.002), and 4.9 +/- 1.6 and 5.9 +/- 0.3 (p = 0.008), respectively. In conclusion,
      baseline knowledge of the ABI test was poor among a sample of internal medicine
      residents. These results suggest that instruction regarding the ABI test is
      deficient in medical school and residency programs and requires action by those
      responsible for the education of medical students and residents.

PMID- 20133344
TI  - High resolution electron transfer dissociation studies of unfractionated intact
      histones from murine embryonic stem cells using on-line capillary LC separation:
      determination of abundant histone isoforms and post-translational modifications.
AB  - Epigenetic regulation of chromatin is dependent on both the histone protein
      isoforms and state of their post-translational modifications. The assignment of
      all post-translational modification sites for each individual intact protein
      isoform remains an experimental challenge. We present an on-line reversed phase
      LC tandem mass spectrometry approach for the separation of intact, unfractionated
      histones and a high resolution mass analyzer, the Orbitrap, with electron
      transfer dissociation capabilities to detect and record accurate mass values for
      the molecular and fragment ions observed. From a single LC-electron transfer
      dissociation run, this strategy permits the identification of the most abundant
      intact proteins, determination of the isoforms present, and the localization of
      post-translational modifications.

PMID- 20133345
TI  - IgA nephropathy in a patient with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is generally recognized to be a multisystem
      autoimmune disease with kidney involvement. However, the occurrence of other non
      lupus glomerulopathies has been rarely reported in patients with systemic lupus
      erythematosus. It is well known that lupus nephritis may switch over time to
      another class according to the World Health Organization classification. It seems
      likely that IgA nephropathy is a clinical characteristic of a particular subset
      of patients with systemic lupus erythematosus. We report a 22-year-old Japanese
      man with recurrence of proteinuria. The renal flare occurred when he was without
      lupus clinical and serological activity, and renal remission was only obtained
      with angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker
      therapy. Although the incidence of IgA nephropathy is high in Japan, we believe
      that this is the first report of a Japanese patient in which lupus nephritis
      switched over time to IgA nephropathy.

PMID- 20133346
TI  - Periodic lateralized epileptiform discharges in neuropsychiatric lupus:
      association with cerebritis in magnetic resonance imaging and resolution after
      intravenous immunoglobulin.
AB  - A 13-year-old girl with a known diagnosis of systemic lupus erythematosus
      presented with seizures and psychosis. An electroencephalogram (EEG) revealed
      continuous, non-evolving periodic lateralized epileptiform discharges (PLEDs) in
      the left temporal region, which did not resolve with benzodiazepine. A magnetic
      resonance imaging (MRI) brain scan demonstrated a focal hyperintensity in the
      left medial temporal and left occipital lobes, left thalamus and bilateral
      cerebellar white matter, with evidence of vasculitis in the magnetic resonance
      angiography. Intravenous immunoglobulin was given because of failed steroid
      therapy, which resulted in a full resolution of clinical, EEG and MRI
      abnormalities. Lupus cerebritis should be considered as a possible aetiology in
      PLEDs, and immunoglobulin can be effective in neuropsychiatric lupus.

PMID- 20133347
TI  - Neonatal lupus erythematosus: a possible role for anti-Sm antibodies.

PMID- 20133348
TI  - Late onset of pANCA renal and pulmonary vasculitis in a girl affected by
      undifferentiated connective tissue disease.
AB  - Vasculitides are clinicopathologic entities characterized by inflammation and
      damage of blood vessels. They are heterogeneous diseases related to
      immunopathogenetic mechanisms. For example, anti-neutrophil cytoplasmic
      autoantibodies directed against perinuclear or cytoplasmic proteins of
      neutrophils are present in a high percentage of patients with systemic
      vasculitis, and they can be suggestive of Wegener's Granulomatosis and
      Microscopic Polyangiitis. This case report underlines the necessity of more
      specific laboratory and instrumental testing if clinical signs and/or other
      parameters (p-ANCA and/or c-ANCA staining and/or urinalysis) are suggestive of
      systemic vasculitis.

PMID- 20133349
TI  - Arterial and venous thrombosis is associated with different angiogenic cytokine
      patterns in patients with antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is defined as a combination of antiphospholipid
      antibodies, arterial and/or venous thrombosis, and, in women, recurrent fetal
      loss. The mechanisms underlying this prothrombotic tendency are unclear. Here we
      determined plasma levels of the angiogenic growth factors vascular endothelial
      growth factor (VEGF), placental growth factor (PlGF) and stromal cell-derived
      factor-1 (SDF-1) in 34 patients with APS (median age 40 years) compared with 180
      healthy controls and with 80 age-matched deep-venous thrombosis patients in whom
      the diagnosis of APS had been excluded. All of the patients met updated APS
      criteria and two-thirds of them were triply positive for antiphospholipid
      antibodies (lupus anticoagulant, anti-beta2-glycoprotein I and anti-cardiolipin
      antibodies). Angiogenic cytokines were quantified at least 6 months after an
      acute thrombotic event. VEGF levels were similar in the patients and controls,
      but were significantly higher in the patients with arterial thrombosis than in
      the patients with venous thrombosis. Plasma levels of SDF-1 and PlGF were
      significantly elevated in the patients, regardless of the arterial/venous nature
      of the thrombosis. Together, these results suggest that APS is associated with an
      angiogenic process, but that the angiogenic signal differs between patients with
      arterial and venous thrombosis. Lupus (2010) 19, 837-843.

PMID- 20133350
TI  - The single nucleotide polymorphisms gene but not the copy number variation of
      Fcgr3B is associated with lupus nephritis in Chinese people.

PMID- 20133351
TI  - Characterization of periplastidal compartment-targeting signals in
      chlorarachniophytes.
AB  - Secondary plastids are acquired by the engulfment and retention of eukaryotic
      algae, which results in an additional surrounding membrane or pair of membranes
      relative to the more familiar primary plastids of land plants. In most cases, the
      endocytosed alga loses its eukaryotic genome as it becomes integrated, but in two
      algal groups, the cryptophytes and chlorarachniophytes, the secondary plastids
      retain a vestigial nucleus in the periplastidal compartment (PPC), the remnant
      eukaryotic cytoplasm between the inner and the outer membrane pairs. Many
      essential housekeeping genes are missing from these reduced genomes, suggesting
      that they are now encoded in the host nucleus and their products are targeted to
      the PPC. One such nucleus-encoded, PPC-targeted protein, the translation
      elongation factor like (EFL) was recently identified in chlorarachniophytes. It
      bears an N-terminal-targeting sequence comprising a signal peptide and a transit
      peptide-like sequence (TPL) similar to the plastid-targeted proteins of
      chlorarachniophytes as well as a hydrophilic C-terminal extension rich in lysine
      and aspartic acid. Here, we characterize the function of the N- and C-terminal
      extensions of PPC-targeted EFL in transformed chlorarachniophyte cells. Using
      green fluorescent protein as a reporter molecule, we demonstrate that several
      negatively charged amino acids within the TPL are essential for accurate
      targeting to the PPC. Our findings further reveal that the C-terminal extension
      functions as a PPC retention signal in combination with an N-terminal plastid
      targeting peptide, which suggests that plastid and PPC proteins may be sorted in
      the PPC.

PMID- 20133352
TI  - Gene conversion and DNA sequence polymorphism in the sex-determination gene fog-2
      and its paralog ftr-1 in Caenorhabditis elegans.
AB  - Gene conversion, a form of concerted evolution, bears enormous potential to shape
      the trajectory of sequence and functional divergence of gene paralogs subsequent
      to duplication events. fog-2, a sex-determination gene unique to Caenorhabditis
      elegans and implicated in the origin of hermaphroditism in this species, resulted
      from the duplication of ftr-1, an upstream gene of unknown function. Synonymous
      sequence divergence in regions of fog-2 and ftr-1 (excluding recent gene
      conversion tracts) suggests that the duplication occurred 46 million generations
      ago. Gene conversion between fog-2 and ftr-1 was previously discovered in
      experimental fog-2 knockout lines of C. elegans, whereby hermaphroditism was
      restored in mutant obligately outcrossing male-female populations. We analyzed
      DNA-sequence variation in fog-2 and ftr-1 within 40 isolates of C. elegans from
      diverse geographic locations in order to evaluate the contribution of gene
      conversion to genetic variation in the two gene paralogs. The analysis shows that
      gene conversion contributes significantly to DNA-sequence diversity in fog-2 and
      ftr-1 (22% and 34%, respectively) and may have the potential to alter sexual
      phenotypes in natural populations. A radical amino acid change in a conserved
      region of the F-box domain of fog-2 was found in natural isolates of C. elegans
      with significantly lower fecundity. We hypothesize that the lowered fecundity is
      due to reduced masculinization and less sperm production and that amino acid
      replacement substitutions and gene conversion in fog-2 may contribute
      significantly to variation in the degree of inbreeding and outcrossing in natural
      populations.

PMID- 20133353
TI  - Role of introduction history and landscape in the range expansion of brown trout
      (Salmo trutta L.) in the Kerguelen Islands.
AB  - Human-mediated biological invasions constitute interesting case studies to
      understand evolutionary processes, including the role of founder effects.
      Population expansion of newly introduced species can be highly dependant on
      barriers caused by landscape features, but identifying these barriers and their
      impact on genetic structure is a relatively recent concern in population genetics
      and ecology. Salmonid populations of the Kerguelen Islands archipelago are a
      favorable model system to address these questions as these populations are
      characterized by a simple history of introduction, little or no anthropogenic
      influence, and demographic monitoring since the first introductions. We analyzed
      genetic variation at 10 microsatellite loci in 19 populations of brown trout
      (Salmo trutta L.) in the Courbet Peninsula (Kerguelen Islands), where the
      species, introduced in 3 rivers only, has colonized the whole water system in 40
      years. Despite a limited numbers of introductions, trout populations have
      maintained a genetic diversity comparable with what is found in hatchery or wild
      populations in Europe, but they are genetically structured. The main factor
      explaining the observed patterns of genetic diversity is the history of
      introductions, with each introduced population acting as a source for
      colonization of nearby rivers. Correlations between environmental and genetic
      parameters show that within each "source population" group, landscape
      characteristics (type of coast, accessibility of river mouth, distances between
      rivers, river length ...) play a role in shaping directions and rates of
      migration, and thus the genetic structure of the colonizing populations.

PMID- 20133354
TI  - Ocean currents help explain population genetic structure.
AB  - Management and conservation can be greatly informed by considering explicitly how
      environmental factors influence population genetic structure. Using simulated
      larval dispersal estimates based on ocean current observations, we demonstrate
      how explicit consideration of frequency of exchange of larvae among sites via
      ocean advection can fundamentally change the interpretation of empirical
      population genetic structuring as compared with conventional spatial genetic
      analyses. Both frequency of larval exchange and empirical genetic difference were
      uncorrelated with Euclidean distance between sites. When transformed into
      relative oceanographic distances and integrated into a genetic isolation-by
      distance framework, however, the frequency of larval exchange explained nearly 50
      per cent of the variance in empirical genetic differences among sites over scales
      of tens of kilometres. Explanatory power was strongest when we considered effects
      of multiple generations of larval dispersal via intermediary locations on the
      long-term probability of exchange between sites. Our results uncover meaningful
      spatial patterning to population genetic structuring that corresponds with ocean
      circulation. This study advances our ability to interpret population structure
      from complex genetic data characteristic of high gene flow species, validates
      recent advances in oceanographic approaches for assessing larval dispersal and
      represents a novel approach to characterize population connectivity at small
      spatial scales germane to conservation and fisheries management.

PMID- 20133355
TI  - Periodic versus scale-free patterns in dryland vegetation.
AB  - Two major forms of vegetation patterns have been observed in drylands: nearly
      periodic patterns with characteristic length scales, and amorphous, scale-free
      patterns with wide patch-size distributions. The emergence of scale-free patterns
      has been attributed to global competition over a limiting resource, but the
      physical and ecological origin of this phenomenon is not understood. Using a
      spatially explicit mathematical model for vegetation dynamics in water-limited
      systems, we unravel a general mechanism for global competition: fast spatial
      distribution of the water resource relative to processes that exploit or absorb
      it. We study two possible realizations of this mechanism and identify physical
      and ecological conditions for scale-free patterns. We conclude by discussing the
      implications of this study for interpreting signals of imminent desertification.

PMID- 20133356
TI  - Explosive morphological diversification of spiny-finned teleost fishes in the
      aftermath of the end-Cretaceous extinction.
AB  - The spiny-finned teleost fishes (Acanthomorpha) include nearly one-third of all
      living vertebrate species and assume a bewildering array of bodyplans, but the
      macroevolutionary assembly of modern acanthomorph biodiversity remains largely
      unexplored. Here, I reconstruct the trajectory of morphological diversification
      in this major radiation from its first appearance in the Late Cretaceous to the
      Miocene using a geometric morphometric database comprising more than 600 extinct
      species known from complete body fossils. The anatomical diversity (disparity) of
      acanthomorphs is low throughout the Cretaceous, increases sharply and
      significantly in the wake of the Cretaceous-Palaeogene (K-P) extinction, and
      shows little change throughout subsequent Cenozoic intervals. This pattern of
      morphological diversification appears robust to two potential biasing factors:
      the 'Lagerstatten effect', and the non-random segregation of rare and common taxa
      along phenotypic axes. Dissecting the trajectory of acanthomorph radiation along
      phylogenetic lines reveals that the abrupt post-extinction increase in disparity
      is driven largely by the proliferation of trophically diverse modern groups
      within Percomorpha, a spiny-fin subclade containing more than 15 000 living
      species and identified as showing a substantially elevated diversification rate
      relative to background vertebrate levels. A major component of the Palaeogene
      acanthomorph radiation reflects colonization of morphospace previously occupied
      by non-acanthomorph victims of the K-P. However, other aspects of morphological
      diversification cannot be explained by this simple ecological release model,
      suggesting that multiple factors contributed to the prolific anatomical radiation
      of acanthomorphs.

PMID- 20133357
TI  - Health spending projections through 2019: the recession's impact continues.
AB  - The economic recession and rising unemployment-plus changing demographics and
      baby boomers aging into Medicare-are among the factors expected to influence
      health spending during 2009-2019. In 2009 the health share of gross domestic
      product (GDP) is expected to have increased 1.1 percentage points to 17.3 percent
      the largest single-year increase since 1960. Average public spending growth rates
      for hospital, physician and clinical services, and prescription drugs are
      expected to exceed private spending growth in the first four years of the
      projections. As a result, public spending is projected to account for more than
      half of all U.S. health care spending by 2012.

PMID- 20133358
TI  - Top-down engagement modulates the neural expressions of visual expertise.
AB  - Perceptual expertise is traditionally associated with enhanced brain activity in
      response to objects of expertise in category-selective visual cortex, primarily
      face-selective regions. We reevaluated this view by investigating whether the
      brain activity associated with expertise in object recognition is limited to
      category-selective cortex and specifically whether the extent of expertise
      related activity manifests automatically or whether it can be top-down modulated.
      We conducted 2 functional magnetic resonance imaging studies comparing changes in
      hemodynamic activity associated with car expertise in a conventional 1-back task
      (Experiment 1) and when the task relevance of cars was explicitly manipulated
      (Experiment 2). Whole-brain analysis unveiled extensive expertise-related
      activity throughout the visual cortex, starting as early as V1 and extending into
      nonvisual areas. However, when the cars were task irrelevant, the expertise
      related activity drastically diminished, indeed, becoming similar to the activity
      elicited by cars in novices. We suggest that expertise entails voluntary top-down
      engagement of multiple neural networks in addition to stimulus-driven activation
      associated with perceptual mechanisms.

PMID- 20133359
TI  - Ursolic acid attenuates D-galactose-induced inflammatory response in mouse
      prefrontal cortex through inhibiting AGEs/RAGE/NF-kappaB pathway activation.
AB  - Evidence shows that administration of D-galactose (D-gal) induces reactive oxygen
      species (ROS) production and inflammatory response resulting in neurodegenerative
      changes. Ursolic acid (UA), a triterpenoid compound, has been reported to possess
      antioxidant and anti-inflammatory properties. Our previous studies have
      demonstrated that UA could protect mouse brain against D-gal-induced oxidative
      damage. In the present study, we examined the protective effect of UA against D
      gal-induced inflammatory response in the prefrontal cortex and explored the
      potential mechanism of its action. Our results showed that UA administration
      significantly improved behavioral performance of D-gal-treated mice in step
      through test and Morris water maze task. One of the potential mechanisms of this
      action was decreased advanced glycation end products (AGEs), ROS, and protein
      carbonyl levels in the prefrontal cortex of D-gal-treated mice. Furthermore, the
      results also showed that UA significantly reduced the number of activated
      microglia cells and astrocytes, decreased the expression of CD11b and glial
      fibrillary acidic protein, downregulated the expression of iNOS and COX-2, and
      decreased interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha levels in
      the prefrontal cortex of D-gal-treated mice. Moreover, UA significantly decreased
      AGEs induced the expression of receptor for advanced glycation end products and
      inhibited NF-kappaB p65 nuclear translocation in the prefrontal cortex of D-gal
      treated mice. The aforementioned effects of UA could attenuate brain inflammatory
      response.

PMID- 20133360
TI  - Identification of two scyllo-inositol dehydrogenases in Bacillus subtilis.
AB  - scyllo-Inositol (SI) is a stereoisomer of inositol whose catabolism has not been
      characterized in bacteria. We found that Bacillus subtilis 168 was able to grow
      using SI as its sole carbon source and that this growth was dependent on a
      functional iol operon for catabolism of myo-inositol (MI; another inositol
      isomer, which is abundant in nature). Previous studies elucidated the MI
      catabolic pathway in B. subtilis as comprising multiple stepwise reactions
      catalysed by a series of Iol enzymes. The first step of the pathway converts MI
      to scyllo-inosose (SIS) and involves the MI dehydrogenase IolG. Since IolG does
      not act on SI, we suspected that there could be another enzyme converting SI into
      SIS, namely an SI dehydrogenase. Within the whole genome, seven genes paralogous
      to iolG have been identified and two of these, iolX and iolW (formerly known as
      yisS and yvaA, respectively), were selected as candidate genes for the putative
      SI dehydrogenase since they were both prominently expressed when B. subtilis was
      grown on medium containing SI. iolX and iolW were cloned in Escherichia coli and
      both were shown to encode a functional enzyme, revealing the two distinct SI
      dehydrogenases in B. subtilis. Since inactivation of iolX impaired growth with SI
      as the carbon source, IolX was identified as a catabolic enzyme required for SI
      catabolism and it was shown to be NAD(+) dependent. The physiological role of
      IolW remains unclear, but it may be capable of producing SI from SIS with NADPH
      oxidation.

PMID- 20133361
TI  - Diversity of CRISPR loci in Escherichia coli.
AB  - CRISPR (clustered regularly interspaced short palindromic repeats) and CAS
      (CRISPR-associated sequence) proteins are constituents of a novel genetic barrier
      that limits horizontal gene transfer in prokaryotes by means of an
      uncharacterized mechanism. The fundamental discovery of small RNAs as the guides
      of the defence apparatus arose as a result of Escherichia coli studies. However,
      a survey of the system diversity in this species in order to further contribute
      to the understanding of the CRISPR mode of action has not yet been performed.
      Here we describe two CRISPR/CAS systems found in E. coli, following the analysis
      of 100 strains representative of the species' diversity. Our results substantiate
      different levels of activity between loci of both CRISPR types, as well as
      different target preferences and CRISPR relevances for particular groups of
      strains. Interestingly, the data suggest that the degeneration of one CRISPR/CAS
      system in E. coli ancestors could have been brought about by self-interference.

PMID- 20133362
TI  - An archaeal order with multiple minichromosome maintenance genes.
AB  - In eukaryotes, a complex of six highly related minichromosome maintenance (MCM)
      proteins is believed to function as the replicative helicase. Until recently,
      systems for exploring the molecular mechanisms underlying eukaryotic MCM function
      have been biochemically intractable. To overcome this, molecular studies of MCM
      function have been carried out using MCM homologues from the archaea. Archaeal
      MCM systems studied to date possess a single functional MCM, which forms a
      homohexameric complex that displays DNA binding, ATPase and helicase activities.
      We have identified an archaeal order that possesses multiple MCM homologues.
      blast searches of available Methanococcales genomes reveal that members of this
      order possess between two and eight MCM homologues. Phylogenetic analysis
      suggests that an ancient duplication in the Methanococcales gave rise to two
      major groups of MCMs. One group contains Methanococcus maripaludis S2 McmD and
      possesses a conserved C-terminal insert similar to one observed in eukaryotic
      MCM3, while the other group contains McmA, -B and -C. Analysis of the genome
      context of MCMs in the latter group indicates that these genes could have arisen
      from phage-mediated events. When co-expressed in Escherichia coli, the four MCMs
      from M. maripaludis co-purify, indicating the formation of heteromeric complexes
      in vitro. The presence of homologues from both groups in all Methanococcales
      indicates that there could be functionally important differences between these
      proteins and that Methanococcales MCMs may therefore provide an interesting
      additional model for eukaryotic MCM function.

PMID- 20133363
TI  - Isethionate formation from taurine in Chromohalobacter salexigens: purification
      of sulfoacetaldehyde reductase.
AB  - Bacterial generation of isethionate (2-hydroxyethanesulfonate) from taurine (2
      aminoethanesulfonate) by anaerobic gut bacteria was established in 1980. That
      phenomenon in pure culture was recognized as a pathway of assimilation of taurine
      nitrogen. Based on the latter work, we predicted from genome-sequence data that
      the marine gammaproteobacterium Chromohalobacter salexigens DSM 3043 would
      exhibit this trait. Quantitative conversion of taurine to isethionate, identified
      by mass spectrometry, was confirmed, and the taurine-nitrogen was recovered as
      cell material. An eight-gene cluster was predicted to encode the inducible
      vectorial, scalar and regulatory enzymes involved, some of which were known from
      other taurine pathways. The genes (Csal_0153-Csal_0156) encoding a putative ATP
      binding-cassette (ABC) transporter for taurine (TauAB(1)B(2)C) were shown to be
      inducibly transcribed by reverse transcription (RT-) PCR. An inducible taurine :
      2-oxoglutarate aminotransferase [EC 2.6.1.55] was found (Csal_0158); the reaction
      yielded glutamate and sulfoacetaldehyde. The sulfoacetaldehyde was reduced to
      isethionate by NADPH-dependent sulfoacetaldehyde reductase (IsfD), a member of
      the short-chain alcohol dehydrogenase superfamily. The 27 kDa protein (SDS-PAGE)
      was identified by peptide-mass fingerprinting as the gene product of Csal_0161.
      The putative exporter of isethionate (IsfE) is encoded by Csal_0160; isfE was
      inducibly transcribed (RT-PCR). The presumed transcriptional regulator, TauR
      (Csal_0157), may autoregulate its own expression, typical of GntR-type
      regulators. Similar gene clusters were found in several marine and terrestrial
      gammaproteobacteria, which, in the gut canal, could be the source of not only
      mammalian, but also arachnid and cephalopod isethionate.

PMID- 20133364
TI  - Interleukin-8 (CXCL8) stimulates trophoblast cell migration and invasion by
      increasing levels of matrix metalloproteinase (MMP)2 and MMP9 and integrins
      alpha5 and beta1.
AB  - Interleukin-8 (IL8/CXCL8) is present in decidua and trophoblast, which also
      expresses the IL8 receptors, CXCR1 and CXCR2. IL8 was shown to stimulate
      trophoblast migration. Matrix metalloproteinase (MMP)2, MMP9, and integrins
      alpha(5)beta(1) and alpha(1)beta(1) were found to play important roles in
      trophoblast invasion. We hypothesized that IL8 would increase this cell migration
      and invasion by HTR-8/SVneo cells through the activity of MMPs and integrins.
      Isolated first trimester of pregnancy cytotrophoblast (CT) and HTR-8/SVneo cell
      line were used. Migration was studied by monolayer wounding test, and invasion by
      Matrigel invasion test. The effects of IL8 on MMPs and integrin subunit
      expression were determined in HTR-8/SVneo cells by gelatin zymography and western
      blot respectively. The results that were obtained showed that exogenous IL8
      stimulated HTR-8/SVneo cell migration and invasion. MMP2 and MMP9 levels were
      stimulated to 182% (P<0.01) and 134% (P<0.01) respectively. Integrin alpha(5)
      expression was increased to 119% (P<0.05) and integrin beta(1) expression to 173%
      (P<0.001) of the control values. The data that were obtained show for the first
      time the sensitivity of the HTR-8/SVneo cells, in addition to isolated first
      trimester CT, to IL8. Exogenous IL8/CXCL8 increased trophoblast cell migration
      and invasion, which may be partly attributable to stimulation of MMP2 and MMP9
      levels and an increase in integrins. HTR-8/SVneo cell viability and proliferation
      were also increased.

PMID- 20133365
TI  - Sustaining reductions in catheter related bloodstream infections in Michigan
      intensive care units: observational study.
AB  - OBJECTIVES: To evaluate the extent to which intensive care units participating in
      the initial Keystone ICU project sustained reductions in rates of catheter
      related bloodstream infections. Design Collaborative cohort study to implement
      and evaluate interventions to improve patients' safety. SETTING: Intensive care
      units predominantly in Michigan, USA. INTERVENTION: Conceptual model aimed at
      improving clinicians' use of five evidence based recommendations to reduce rates
      of catheter related bloodstream infections rates, with measurement and feedback
      of infection rates. During the sustainability period, intensive care unit teams
      were instructed to integrate this intervention into staff orientation, collect
      monthly data from hospital infection control staff, and report infection rates to
      appropriate stakeholders. MAIN OUTCOME MEASURES: Quarterly rate of catheter
      related bloodstream infections per 1000 catheter days during the sustainability
      period (19-36 months after implementation of the intervention). RESULTS: Ninety
      (87%) of the original 103 intensive care units participated, reporting 1532
      intensive care unit months of data and 300 310 catheter days during the
      sustainability period. The mean and median rates of catheter related bloodstream
      infection decreased from 7.7 and 2.7 (interquartile range 0.6-4.8) at baseline to
      1.3 and 0 (0-2.4) at 16-18 months and to 1.1 and 0 (0.0-1.2) at 34-36 months post
      implementation. Multilevel regression analysis showed that incidence rate ratios
      decreased from 0.68 (95% confidence interval 0.53 to 0.88) at 0-3 months to 0.38
      (0.26 to 0.56) at 16-18 months and 0.34 (0.24-0.48) at 34-36 months post
      implementation. During the sustainability period, the mean bloodstream infection
      rate did not significantly change from the initial 18 month post-implementation
      period (-1%, 95% confidence interval -9% to 7%). CONCLUSIONS: The reduced rates
      of catheter related bloodstream infection achieved in the initial 18 month post
      implementation period were sustained for an additional 18 months as participating
      intensive care units integrated the intervention into practice. Broad use of this
      intervention with achievement of similar results could substantially reduce the
      morbidity and costs associated with catheter related bloodstream infections.

PMID- 20133367
TI  - Management of polymyalgia rheumatica.

PMID- 20133370
TI  - Stem cell researchers claim some reviewers hamper publication of high quality
      research.

PMID- 20133372
TI  - The transcriptome of Nrf2-/- mice provides evidence for impaired cell cycle
      progression in the development of cigarette smoke-induced emphysematous changes.
AB  - Cigarette smoke (CS) imposes a strong oxidative burden on exposed tissues
      resulting in a severely disturbed oxidant/antioxidant balance, which in the
      context of chronic exposure is assumed to be a key contributor to CS-related
      diseases. Because of its emerging central role in orchestrating the general
      cellular antioxidant response, the pathway leading to the activation of the
      transcription factor Nrf2 has received mounting attention over the past decade in
      investigations aimed at elucidating CS-induced pathophysiological mechanisms. To
      comprehensively characterize the impact of Nrf2 in acute and subchronic smoking
      scenarios, Nrf2(-/-) mice and their wild-type (wt) ICR littermates were exposed
      to either ambient air (sham exposure) or one of three doses of CS for up to 5
      months, with two postexposure endpoints of 1 and 13 days. The lungs of the mice
      were monitored for transcriptomic changes on a genome-wide level, which confirmed
      an impaired expression of antioxidant and phase 2-related genes in CS-exposed
      Nrf2(-/-) mice. Importantly, in comparison to wt mice, an attenuated cell
      cycle/mitotic response and intensified stress gene expression pattern were
      observed in exposed Nrf2(-/-) mice, which was paralleled by clear dose-dependent
      effects on alveolar destruction and impaired lung function. In contrast, the
      inflammation-related transcriptional response and scores for various
      bronchioalveolar inflammation parameters were qualitatively and quantitatively
      similar in CS-exposed mice of both genotypes. Taken together, these results
      confirm the protective nature of Nrf2 in oxidative stress scenarios and suggest
      that the enhanced emphysematous phenotype exhibited by CS-exposed Nrf2(-/-) mice
      is more likely caused by an imbalance in cell loss and regeneration than by
      increased inflammation.

PMID- 20133373
TI  - Gene expression analysis reveals a gene set discriminatory to different metals in
      soil.
AB  - Environmental pollution is a worldwide problem, and metals are the largest group
      of contaminants in soil. Microarray toxicogenomic studies with ecologically
      relevant organisms, such as springtails, supplement traditional ecotoxicological
      research but are presently rather descriptive. Classifier analysis, a more
      analytical application of the microarray technique, is able to predict biological
      classes of unknown samples. We used the uncorrelated shrunken centroid method to
      classify gene expression profiles of the springtail Folsomia candida exposed to
      soil spiked with six different metals (barium, cadmium, cobalt, chromium, lead,
      and zinc). We identified a gene set (classifier) of 188 genes that can
      discriminate between six different metals present in soil, which allowed us to
      predict the correct classes for samples of an independent test set with an
      accuracy of 83% (error rate = 0.17). This study shows further that in order to
      apply classifier analysis to actual contaminated field soil samples, more insight
      and information is needed on the transcriptional responses of soil organisms to
      different soil types (properties) and mixtures of contaminants.

PMID- 20133374
TI  - Endocytosis in cultured neurons is altered by chronic alcohol exposure.
AB  - Endocytosis is required for many cellular pivotal processes, including membrane
      recycling, nutrient uptake, and signal transduction. This complex process is
      particularly relevant in polarized cells, such as neurons. Previous studies have
      demonstrated that alcohol alters intracellular traffic, including endocytosis, in
      several cell types. However, information on the effect of chronic alcohol
      exposure on this process in neurons is scarce. As an approach, we investigated
      the effect of alcohol exposure on the internalization of two widely used
      endocytic markers, albumin and transferrin, in developing hippocampal neurons in
      primary culture. The effect of this treatment on the levels of several
      representative proteins involved in the endocytic process was also analyzed. Some
      of these proteins are also involved in the organization of the actin
      cytoskeleton. Pretreatment of cells with inhibitors chlorpromazine or nystatin
      indicates that albumin is internalized mainly by caveolin-dependent endocytosis.
      On the other hand, alcohol decreases the endocytosis of both markers, although no
      qualitative changes in the distribution of either of these molecules were
      observed. Finally, the effect of ethanol on the proteins analyzed was
      heterogeneous. Alcohol decreases the levels of clathrin, AP-2, SNX9, Rab5, Rab11,
      EEA1, Cdc42, or RhoA but increases the amount of Arf6. Moreover, alcohol does not
      affect the levels of caveolin1, dynamin1, Rab7, and LAMP2. This toxic effect of
      alcohol on endocytosis could affect some of the important neuronal activities,
      which depend on this process, including cell signaling. Our results in neurons
      also stress the notion that one of the main targets of ethanol is intracellular
      transport.

PMID- 20133375
TI  - Protective and damaging effects of platelets in acute cholestatic liver injury
      revealed by depletion and inhibition strategies.
AB  - Alpha-naphthylisothiocyanate (ANIT) causes cholestatic hepatitis characterized by
      intrahepatic bile duct epithelial cell injury and periportal hepatocellular
      necrosis. The progression of ANIT-induced hepatocyte injury is reported to
      involve extrahepatic cells including platelets. We showed recently that the
      procoagulant protein tissue factor (TF) is essential for ANIT-induced coagulation
      and contributes to ANIT-induced liver necrosis. Platelets have been shown to
      express TF and can contribute to coagulation cascade activation. To this end, we
      tested the hypothesis that platelet-dependent coagulation contributes to ANIT
      induced liver injury. In ANIT (60 mg/kg)-treated mice, activation of the
      coagulation cascade occurred prior to a decrease of platelets in the blood.
      Immunostaining for glycoprotein IIb (CD41) revealed platelet accumulation along
      the borders of necrotic foci in livers of ANIT-treated mice. Antibody-mediated
      platelet depletion did not affect coagulation but markedly affected liver
      histopathology in ANIT-treated mice. Platelet depletion induced marked pooling of
      blood within necrotic lesions consistent with parenchymal-type peliosis as early
      as 24 h after ANIT treatment. In contrast, treatment with the P2Y(12) inhibitor
      clopidogrel significantly reduced ANIT-induced hepatocyte necrosis and serum
      alanine aminotransferase activity but did not exaggerate bleeding into necrotic
      foci. Clopidogrel also reduced hepatic neutrophil accumulation but did not affect
      induction of Intercellular adhesion molecule-1 or chemokine CxC motif ligand-1
      messenger RNA expression in liver. The data indicate that ANIT-induced
      coagulation is platelet independent and that platelets contribute to ANIT-induced
      hepatocyte necrosis by promoting neutrophil accumulation. In contrast, severe
      thrombocytopenia induces parenchymal-type peliosis in the livers of ANIT-treated
      mice, a rare hepatic lesion associated with pooling of blood in the liver.

PMID- 20133376
TI  - A possible neuroprotective action of a vinylic telluride against Mn-induced
      neurotoxicity.
AB  - Manganese (Mn) is a metal required by biological systems. However, environmental
      or occupational exposure to high levels of Mn can produce a neurological disorder
      called manganism, which has similarities to Parkinson's disease. Diethyl-2-phenyl
      2-tellurophenyl vinylphosphonate (DPTVP) is an organotellurium compound with a
      high antioxidant activity, especially in the brain. The present study was
      designed to investigate the effects of long-term low-dose exposure to Mn in
      drinking water on behavioral and biochemical parameters in rats and to determine
      the effectiveness of vinylic telluride in attenuating the effects of Mn. After 4
      months of treatment with MnCl(2) (13.7 mg/kg), rats exhibited clear signs of
      neurobehavioral toxicity, including a decrease in the number of rearings in the
      open field and altered motor performance in rotarod. The administration of DPTVP
      (0.150 micromol/kg, ip, 2 weeks) improved the motor performance of Mn-treated
      rats, indicating that the compound could be reverting Mn neurotoxicity. Ex vivo,
      we observed that Mn concentrations in the Mn-treated group were highest in the
      striatum, consistent with a statistically significant decrease in mitochondrial
      viability and [(3)H]glutamate uptake, and increased lipid peroxidation. Mn levels
      in the hippocampus and cortex were indistinguishable from controls, and no
      significant differences were noted in the ex vivo assays in these areas.
      Treatment with DPTVP fully reversed the biochemical parameters altered by Mn.
      Furthermore, DPTVP treatment was also associated with a reduction in striatal Mn
      levels. Our results demonstrate that DPTVP has neuroprotective activity against
      Mn-induced neurotoxicity, which may be attributed to its antioxidant activity
      and/or its effect on striatal Mn transport.

PMID- 20133379
TI  - Do smokers crave cigarettes in some smoking situations more than others?
      Situational correlates of craving when smoking.
AB  - INTRODUCTION: Smokers tend to smoke when experiencing craving, but even within
      smoking occasions, craving may vary. We examine variations in craving when people
      were smoking in various real-world situations. METHODS: Using Ecological
      Momentary Assessment, 394 smokers recorded smoking, craving, and smoking context
      in real time on electronic diaries over 2 weeks of ad libitum smoking.
      Assessments occurred immediately prior to smoking. Mixed modeling was used to
      analyze associations between craving and situational variables. RESULTS: Craving
      varied across smoking situations, but the differences were small (<1 on a 0-10
      scale). Specifically, craving was higher in smoking situations where smoking was
      restricted, likely because high craving leads smokers to violate restrictions.
      Controlling for restrictions, craving was higher when cigarettes were smoked
      while eating or drinking, were with other people (vs. alone), were in a group of
      people (vs. other people simply in view), during work (vs. leisure), and during
      activity (vs. inactivity). In addition, craving was higher for cigarettes smoked
      early in the day. No differences in craving were observed in relation to drinking
      alcohol or caffeine (vs. doing anything else), being at work (vs. home), being at
      a bar or restaurant (vs. all other locations), interacting with others (vs. not
      interacting), or other people smoking (vs. no others smoking). DISCUSSION: Even
      though most craving reports prior to smoking were high, and situations were thus
      expected to have little influence on craving, results suggest that some
      cigarettes are craved more than others across different smoking situations, but
      differences are small.

PMID- 20133380
TI  - Sleep disorders and secondhand smoke exposure in the U.S. population.
AB  - INTRODUCTION: Sleep disorders in the United States are pervasive and have been
      linked to increased risk of injury, morbidity, and mortality. Smoking is a known
      risk factor for sleep disorders; the association between secondhand smoke (SHS)
      exposure and sleep disorders is less clear. We sought to examine the relationship
      between SHS exposure and sleep disorders among a representative sample of U.S.
      adults (n = 4,123). METHODS: Data were from the 2005-2006 National Health and
      Nutrition Examination Survey. Multivariable logistic regression models examined
      the association between both smoking and SHS exposure with two measures of sleep
      disorder (i.e., self-reported health care provider diagnosis and self-report of
      two or more sleep symptoms). SHS exposure status was based on a combination of
      self-report and serum cotinine levels. RESULTS: Relative to nonsmokers without
      SHS exposure, smokers were significantly more likely to have been diagnosed with
      a sleep disorder (odds ratio [OR] = 1.73 [95% CI = 1.16-2.60]) and more likely to
      report at least two sleep disorder symptoms (OR = 1.42 [95% CI = 1.09-1.84]). SHS
      exposed nonsmokers were not significantly more likely to report a sleep disorder
      or sleep symptoms (OR = 1.43 [95% CI = 0.79-2.57] and OR = 1.03 [95% CI = 0.83
      1.27]), respectively. DISCUSSION: Although smoking appears to play an important
      role in the prevalence of sleep disorders in the U.S. adult population, the role
      of SHS exposure is inconclusive and warrants further investigation.

PMID- 20133381
TI  - Sex differences in TTC12/ANKK1 haplotype associations with daily tobacco smoking
      in Black and White Americans.
AB  - INTRODUCTION: The 11q23.1 genomic region has been associated with nicotine
      dependence in Black and White Americans. METHODS: By conducting linkage
      disequilibrium analyses of 7 informative single nucleotide polymorphisms (SNPs)
      within the tetratricopeptide repeat domain 12 (TTC12)/ankyrin repeat and kinase
      containing 1 (ANKK1)/dopamine (D2) receptor gene cluster, we identified haplotype
      block structures in 270 Black and 368 White (n = 638) participants, from the
      Baltimore Epidemiologic Catchment Area cohort study, spanning the TTC12 and ANKK1
      genes consisting of three SNPs (rs2303380-rs4938015-rs11604671). Informative
      haplotypes were examined for sex-specific associations with daily tobacco smoking
      initiation and cessation using longitudinal data from 1993-1994 and 2004-2005
      interviews. RESULTS: There was a Haplotype x Sex interaction such that Black men
      possessing the GTG haplotype who were smokers in 1993-2004 were more likely to
      have stopped smoking by 2004-2005 (55.6% GTG vs. 22.0% other haplotypes), while
      Black women were less likely to have quit smoking if they possessed the GTG
      (20.8%) versus other haplotypes (24.0%; p = .028). In Whites, the GTG haplotype
      (vs. other haplotypes) was associated with lifetime history of daily smoking
      (smoking initiation; odds ratio = 1.6; 95% CI = 1.1-2.4; p = .013). Moreover,
      there was a Haplotype x Sex interaction such that there was higher prevalence of
      smoking initiation with GTG (77.6%) versus other haplotypes (57.0%; p = .043).
      DISCUSSION: In 2 different ethnic American populations, we observed man-woman
      variation in the influence of the rs2303380-rs4938015-rs11604671 GTG haplotype on
      smoking initiation and cessation. These results should be replicated in larger
      cohorts to establish the relationship among the rs2303380-rs4938015-rs11604671
      haplotype block, sex, and smoking behavior.

PMID- 20133382
TI  - Enhancing activity and overcoming chemoresistance in hematologic malignancies
      with bortezomib: preclinical mechanistic studies.
AB  - BACKGROUND: Proteasome inhibition results in antitumor activity through various
      mechanisms, including disruption of cell cycle progression and control, induction
      of apoptosis, and inhibition of proliferation. DESIGN: This review assesses
      preclinical data on the ability of bortezomib, the first proteasome inhibitor
      approved for clinical use, to enhance antitumor activity of other agents and to
      overcome chemoresistance in hematologic malignancies and discusses mechanisms by
      which such activity arises. RESULTS: Bortezomib has been shown to affect multiple
      cellular pathways and levels of numerous intracellular proteins, including
      targets of importance in hematologic malignancies. These mechanisms have shown
      additive or synergistic effects in vitro and in vivo with those of conventional
      therapeutic and novel targeted agents. Additionally, targets of proteasome
      inhibition are implicated in resistance or lack of sensitivity to different
      therapies. Bortezomib in combination with other agents has been shown to overcome
      resistance to those agents and to resensitize cells to agents to which they were
      previously unresponsive. CONCLUSIONS: This review indicates the potential utility
      of proteasome inhibition for substantially enhancing activity of other
      therapeutic approaches. It explains the mechanisms responsible for the observed
      clinical activity of bortezomib-based regimens and elucidates novel therapeutic
      approaches through identification of combinations of agents with complimentary
      mechanisms of action.

PMID- 20133383
TI  - Investigator-initiated trials of targeted oncology agents: why independent
      research is at risk?
AB  - BACKGROUND: Drug development traditionally has relied upon the complementary
      contributions of clinicians and scientists at academic institutions and at
      pharmaceutical companies. Greater regulatory burdens, increased bureaucratic
      requirements, restricted reimbursement, and spiralling research and development
      costs are exerting pressure on the drug development pipeline. The result is a de
      emphasis of exploratory research, particularly independent academic research,
      despite its proven value in identifying new drug targets and developing
      innovative cancer therapies. DESIGN: An expert panel assembled by the Biotherapy
      Development Association-a nonprofit international forum for academic and industry
      researchers, patients, and government regulatory and postregulatory agencies
      examined the growing schism between academia and industry and identified several
      causes of declining academic research. RESULTS: The authors propose solutions to
      sustain investigator-initiated research and provide a new model whereby expert
      organisations provide a forum for academia and industry to plan studies within a
      regulatory framework to support licensure/authorisation and reimbursement for new
      molecularly targeted agents and biomarkers. CONCLUSIONS: Investigator-initiated
      trials have led to the discovery and development of innovative, safe, and
      effective cancer treatments. To ensure that such research continues, action will
      be required on the parts of legislative and regulatory bodies, industry,
      universities, patient advocacy organisations, and preclinical and clinical
      academic scientists.

PMID- 20133384
TI  - Role of bone morphogenetic proteins in adrenal physiology and disease.
AB  - Bone morphogenetic proteins (BMPs) are members of the transforming growth factor
      beta superfamily of ligands that impact on a multitude of biological processes
      including cell type specification, differentiation and organogenesis.
      Furthermore, a large body of evidence points towards important BMP-dependent
      mechanisms in tumorigenesis. In accordance with their diverse actions, BMPs have
      been demonstrated to serve as auto-, para- and endocrine modulators also in a
      number of hormonal systems. In this review, we highlight novel aspects of BMP
      dependent regulatory networks that pertain to adrenal physiology and disease,
      which have been uncovered during recent years. These aspects include the role of
      BMP-dependent mechanism during adrenal development, modulating effects on
      catecholamine synthesis and steroidogenesis and dysregulation of BMP signalling
      in adrenal tumorigenesis. Furthermore, we summarize potential therapeutic
      approaches that are based on reconstitution of BMP signalling in adrenocortical
      tumour cells.

PMID- 20133385
TI  - Targeting mediators of Wnt signalling pathways by GnRH in gonadotropes.
AB  - The binding of GnRH to its receptor on pituitary gonadotropes leads to the
      targeting of a diverse array of signalling mediators. These mediators drive
      multiple signal transduction pathways, which in turn regulate a variety of
      cellular processes, including the biosynthesis and secretion of the gonadotropins
      LH and FSH. Advances in our understanding of the mechanisms and signalling
      pathways that are recruited to regulate gonadotrope function are continually
      being made. This review will focus on the recent demonstration that key mediators
      of the canonical Wnt signalling pathway are targeted by GnRH in gonadotropes, and
      that these may play essential roles in regulating the expression of many of the
      key players in gonadotrope biology, including the GnRH receptor and the
      gonadotropins.

PMID- 20133386
TI  - Psychiatric genocide: reflections and responsibilities.

PMID- 20133387
TI  - Intravascular ultrasound: principles and cerebrovascular applications.
AB  - Intravascular sonography is a valuable tool for the morphologic assessment of
      coronary atherosclerosis and the effect of pharmacologic and nonpharmacologic
      interventions on the progression or stabilization of atherosclerosis. An analysis
      of the different modes, applications, and limitations is provided on the basis of
      review of existing data from multiple clinical case studies, trials, and
      mechanistic studies. Intravascular sonography has been used to assess the
      outcomes of different percutaneous interventions, including angioplasty and stent
      implantation, and to provide detailed characterization of atherosclerotic
      lesions, aneurysms, and dissections within the cerebrovascular circulation.
      Evolution of intravascular sonographic technology has led to the development of
      more sophisticated diagnostic tools such as color-flow, virtual histology, and
      integrated backscatter intravascular sonography. The technologic advancement in
      intravascular sonography has the potential of providing more accurate information
      prior, during, and after a medical or endovascular intervention. Continued
      assessment of this diagnostic technique in both the intracranial and extracranial
      circulation will lead to increased use in clinical practice with the intent to
      improve outcomes.

PMID- 20133388
TI  - MR neurography of neuromas related to nerve injury and entrapment with surgical
      correlation.
AB  - MR imaging of peripheral nerves has been described in relation to abnormalities
      such as nerve injury, entrapment, and neoplasm. Neuroma formation is a known
      response to peripheral nerve injury, and here we correlate the MRN appearance of
      postinjury neuroma formation with intraoperative findings. We also present the MR
      imaging features of surgical treatment with a synthetic nerve tube and nerve wrap
      on postoperative follow-up imaging.

PMID- 20133389
TI  - The emerging echogenic tract sign of pyriform sinus fistula: an early indicator
      in the recovery stage of acute suppurative thyroiditis.
AB  - AST is commonly associated with pyriform sinus-thyroid fistula in children.
      Radiologic findings of AST are documented in a few reports. We report a new sign
      we term the "emerging echogenic tract sign," which reflects a patent air
      containing pyriform sinus-thyroid fistula on follow-up US. Recognition of this
      sign is an important finding suggesting an associated pyriform sinus-thyroid
      fistula in a patient with AST and also suggesting the adequate timing of barium
      esophagography to confirm the fistula.

PMID- 20133391
TI  - Acetylcholinesterase antagonist potentiated insulin action in fed but not fasted
      state.
AB  - The glucose disposal effect of insulin is doubled in response to a meal. This
      meal-induced insulin sensitization results from insulin acting on the liver, in
      the presence of a permissive hepatic parasympathetic feeding signal and elevated
      hepatic glutathione (GSH), to release hepatic insulin-sensitizing substance
      (HISS), a hormone that acts selectively on skeletal muscle to stimulate insulin
      mediated glucose uptake. Blockade of the parasympathetic feeding signal to the
      liver, either through surgical denervation or atropine-mediated antagonism of
      hepatic muscarinic receptors, eliminates the HISS response, resulting in HISS
      dependent insulin resistance (HDIR) and decreasing the response to insulin by
      approximately 55% in the fed state. Insulin action in Sprague-Dawley rats, as
      determined with a rapidly sampled, transient euglycemic clamp in response to
      insulin (50 mU/kg), is decreased in a dose-dependent manner by atropine. In this
      study, we have used the ED75 atropine-induced model of HDIR. After a submaximal
      dose of atropine, potentiation of the remaining parasympathetic effect with the
      acetylcholinesterase antagonist neostigmine significantly restored postprandial
      insulin sensitization in a dose-dependent manner with peak effect at 0.1
      microg/kg/min. Neostigmine reversed the insulin resistance induced by partial
      fasting and partial muscarinic inhibition (hepatic GSH levels are at fed levels),
      but not that induced by surgical hepatic denervation (GSH normal, no nerve
      signal) or 24-h fasting (low GSH). No potentiation of the response to insulin by
      neostigmine occurred in normal, fed rats. The data suggest the use of either
      direct or indirectly acting cholinergic agonists for the treatment of impaired
      postprandial insulin sensitization.

PMID- 20133392
TI  - Molecular basis for a high-potency open-channel block of Kv1.5 channel by the
      endocannabinoid anandamide.
AB  - The endocannabinoid, N-arachidonoylethanolamine (anandamide; AEA) is known to
      interact with voltage-gated K(+) (Kv) channels in a cannabinoid receptor
      independent manner. AEA modulates the functional properties of Kv channels,
      converting channels with slowly inactivating current into apparent fast
      inactivation. In this study, we characterize the mechanism of action and binding
      site for AEA on Kv1.5 channels expressed on HEK-293 cells using the patch-clamp
      techniques. AEA exhibited high-potency block (IC(50) approximately 200 nM) from
      the cytoplasmic membrane surface, consistent with open-channel block. Alanine
      scanning mutagenesis revealed that AEA interacts with two crucial beta-branching
      amino acids, Val505 and Ile508 within the S6 domain. Both residues face toward
      the central cavity and constitute a motif that forms a hydrophobic ring around
      the ion conduction pathway. This hydrophobic ring motif may be a critical
      determinant of cannabinoid receptor-independent AEA modulation in other K(+)
      channel families.

PMID- 20133393
TI  - Extracellular water may mask actual muscle atrophy during aging.
AB  - BACKGROUND: Skeletal muscle tissue holds a large volume of water partitioned into
      extracellular water (ECW) and intracellular water (ICW) fractions. As the ECW may
      not be related to muscle strength directly, we hypothesized that excluding ECW
      from muscle volume would strengthen the correlation with muscle strength.
      METHODS: A total of 119 healthy men aged 20-88 years old participated in this
      study. Knee isometric extension strength, vertical jump, and standing from a
      chair were measured as indices of muscle strength and power in the lower
      extremities. The regional lean volume (LV), total water (TW), ICW, and ECW in the
      lower leg were estimated by anthropometry (skinfold and circumference
      measurements) and segmental multifrequency bioelectrical impedance spectroscopy
      (S-BIS). Then, we calculated the ECW/TW and ICW/TW ratios. RESULTS: Although ICW
      and the LV index decreased significantly with age (p < .001), no significant
      changes in ECW were observed (p = .134). Consequently, the ECW/TW ratio increased
      significantly (p < .001) with age (young adult, 27.0 +/- 2.9%; elderly, 34.3 +/-
      4.9%; advanced elderly, 37.2 +/- 7.0%). Adjusting for this by including the
      ICW/TW ratio in our models significantly improved the correlation between the LV
      index and strength-related measurements and correlated with strength-related
      measurements independently of the LV index (p < .001). CONCLUSIONS: The ECW/TW
      ratio increases in the lower leg with age. The results suggest that the expansion
      of ECW relative to ICW and the LV masked actual muscle cell atrophy with aging.

PMID- 20133390
TI  - Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the
      cytochrome P450 monooxygenases: physiological and pharmacological implications.
AB  - Arachidonoyl ethanolamide (anandamide) is an endogenous amide of arachidonic acid
      and an important signaling mediator of the endocannabinoid system. Given its
      numerous roles in maintaining normal physiological function and modulating
      pathophysiological responses throughout the body, the endocannabinoid system is
      an important pharmacological target amenable to manipulation directly by
      cannabinoid receptor ligands or indirectly by drugs that alter endocannabinoid
      synthesis and inactivation. The latter approach has the possible advantage of
      more selectivity, thus there is the potential for fewer untoward effects like
      those that are traditionally associated with cannabinoid receptor ligands. In
      that regard, inhibitors of the principal inactivating enzyme for anandamide,
      fatty acid amide hydrolase (FAAH), are currently in development for the treatment
      of pain and inflammation. However, several pathways involved in anandamide
      synthesis, metabolism, and inactivation all need to be taken into account when
      evaluating the effects of FAAH inhibitors and similar agents in preclinical
      models and assessing their clinical potential. Anandamide undergoes oxidation by
      several human cytochrome P450 (P450) enzymes, including CYP3A4, CYP4F2, CYP4X1,
      and the highly polymorphic CYP2D6, forming numerous structurally diverse lipids,
      which are likely to have important physiological roles, as evidenced by the
      demonstration that a P450-derived epoxide of anandamide is a potent agonist for
      the cannabinoid receptor 2. The focus of this review is to emphasize the need for
      a better understanding of the P450-mediated pathways of the metabolism of
      anandamide, because these are likely to be important in mediating endocannabinoid
      signaling as well as the pharmacological responses to endocannabinoid-targeting
      drugs.

PMID- 20133394
TI  - Aligning a new reference genetic map of Lupinus angustifolius with the genome
      sequence of the model legume, Lotus japonicus.
AB  - We have developed a dense reference genetic map of Lupinus angustifolius (2n =
      40) based on a set of 106 publicly available recombinant inbred lines derived
      from a cross between domesticated and wild parental lines. The map comprised 1090
      loci in 20 linkage groups and three small clusters, drawing together data from
      several previous mapping publications plus almost 200 new markers, of which 63
      were gene-based markers. A total of 171 mainly gene-based, sequence-tagged site
      loci served as bridging points for comparing the Lu. angustifolius genome with
      the genome sequence of the model legume, Lotus japonicus via BLASTn homology
      searching. Comparative analysis indicated that the genomes of Lu. angustifolius
      and Lo. japonicus are highly diverged structurally but with significant regions
      of conserved synteny including the region of the Lu. angustifolius genome
      containing the pod-shatter resistance gene, lentus. We discuss the potential of
      synteny analysis for identifying candidate genes for domestication traits in Lu.
      angustifolius and in improving our understanding of Fabaceae genome evolution.

PMID- 20133397
TI  - Are physicians obligated always to act in the patient's best interests?
AB  - The principle that physicians should always act in the best interests of the
      present patient is widely endorsed. At the same time, and often within the same
      document, it is recognised that there are appropriate exceptions to this
      principle. Unfortunately, little, if any, guidance is provided regarding which
      exceptions are appropriate and how they should be handled. These circumstances
      might be tenable if the appropriate exceptions were rare. Yet, evaluation of the
      literature reveals that there are numerous exceptions, several of which pervade
      clinical medicine. This situation leaves physicians without adequate guidance on
      when to allow exceptions and how to address them, increasing the chances for
      unfairness in practice. The present article considers the range of exceptions,
      illustrates how the lack of guidance poses ethical concern and describes an
      alternative account of physician obligations to address this concern.

PMID- 20133395
TI  - Cerebral white matter recovery in abstinent alcoholics--a multimodality magnetic
      resonance study.
AB  - Most previous neuroimaging studies of alcohol-induced brain injury and recovery
      thereof during abstinence from alcohol used a single imaging modality. They have
      demonstrated widespread microstructural, macrostructural or metabolite
      abnormalities that were partially reversible with abstinence, with the cigarette
      smoking potentially modulating these processes. The goals of this study were to
      evaluate white matter injury and recovery thereof, simultaneously with diffusion
      tensor imaging, magnetic resonance imaging and spectroscopy in the same cohort;
      and to evaluate the relationships between outcome measures of similar regions. We
      scanned 16 non-smoking and 20 smoking alcohol-dependent individuals at 1 week of
      abstinence from alcohol and 22 non-smoking light drinkers using a 1.5 T magnetic
      resonance scanner. Ten non-smoking alcohol-dependent individuals and 11 smoking
      alcohol-dependent individuals were re-scanned at 1 month of abstinence. All
      regional diffusion tensor imaging, magnetic resonance imaging and spectroscopic
      outcome measures were calculated over comparable volumes of frontal, temporal,
      parietal and occipital white matter. At 1 week of abstinence and relative to non
      smoking light drinkers, non-smoking alcohol-dependent individuals had higher mean
      diffusivity in frontal, temporal and parietal white matter (all P<0.008), whereas
      smoking alcohol-dependent individuals had elevated mean diffusivity only in
      frontal white matter (P=0.03). Smoking alcohol-dependent individuals demonstrated
      lower concentrations of N-acetyl-aspartate (a marker of neuronal viability) in
      frontal white matter (P=0.03), whereas non-smoking alcohol-dependent individuals
      had lower N-acetyl-aspartate in parietal white matter (P=0.05). These
      abnormalities were not accompanied by detectable white matter atrophy. However,
      the patterns of white matter recovery were different between non-smoking alcohol
      dependent individuals and smoking alcohol-dependent individuals. In non-smoking
      alcohol-dependent individuals, the increase in fractional anisotropy of temporal
      white matter (P=0.003) was accompanied by a pattern of decreases mean diffusivity
      in all regions over 1 month of abstinence; no corresponding changes were observed
      in smoking alcohol-dependent individuals. In contrast, a pattern of white matter
      volume increase in frontal and temporal lobes was apparent in smoking alcohol
      dependent individuals but not in non-smoking alcohol-dependent individuals. These
      results were not accompanied by significant changes in metabolite concentrations.
      Finally, there were no consistent patterns of association between measures
      obtained with different imaging modalities, either cross-sectionally or
      longitudinally. These data demonstrate significant white matter improvements with
      abstinence from alcohol, reflected either as microstructural recovery or
      volumetric increases that depend on the smoking status of the participants. We
      believe our results to be important, as they demonstrate that use of a single
      imaging modality provides an incomplete picture of neurobiological processes
      associated with alcohol-induced brain injury and recovery thereof that may even
      lead to improper interpretation of results.

PMID- 20133398
TI  - Skeletal age determination in adolescents involved in judicial procedures: from
      evidence-based principles to medical practice.
AB  - BACKGROUND: The ideal basis of age estimation is considered to be a combination
      of clinical, skeletal and dental examinations. It is not easy to determine how
      forensic physicians take account of evidence-based data obtained from medical
      journals in their medical decision-making. The question of what is an ethically
      acceptable probability that adolescents are incorrectly considered to be over 18
      has not been answered. METHODS: In a retrospective study over 1 year (2007), 498
      files (for 141 female subjects and 357 male subjects) regarding age assessment
      requested by the public prosecutor's office for purposes of criminal or asylum
      proceedings were reviewed. Chronological age was estimated from a combination of
      physical examination, radiographic examination of the left hand and determination
      of dental status. RESULTS: Estimates of chronological age in 498 subjects
      claiming to be 9-14 years old were incompatible with the alleged age in 356 (71%)
      when made by the forensic physician but in only 17 (3%) when based on data from
      published studies on age estimation in adolescents. CONCLUSIONS: The present
      study suggests that in most cases the forensic physician ignores the adolescent's
      word. Medical mission and ethics imply a need to listen to the claims of persons
      in custody, whatever the risk of false claims. This situation should prompt
      forensic physicians to keep up with published data on estimating the age of
      adolescents.

PMID- 20133399
TI  - Apotemnophilia: ethical considerations of amputating a healthy limb.
AB  - Apotemnophilia is a condition that causes those who have it to not feel "correct"
      in their own bodies. As a result, an intense obsession develops with removing the
      limb; this obsession hinders tremendously the patients' social behaviour and
      societal integration. These patients, in some respects resembling transgendered
      individuals, feel that the body part (limb) in question is simply "not a part of
      themselves", causing them to feel uncomfortable in their own bodies. Whether
      amputations should be performed on apotemnophiles or not is a question that poses
      a significant medical ethical dilemma. It is argued that observing an
      apotemnophile's request for amputation is the ethical action. The major arguments
      opposing such amputations and supporting such amputations are examined and
      critically analysed with regard to ethical principles-namely, patient autonomy,
      beneficence, non-maleficence and justice with regard to every person's "right to
      happiness". Finally, a discourse on how the accepted notion of harm does not
      apply to apotemnophilia is developed to justify the position that amputation is
      indeed medically the ethical choice.

PMID- 20133400
TI  - Tailor-made finance versus tailor-made care. Can the state strengthen consumer
      choice in healthcare by reforming the financial structure of long-term care?
AB  - BACKGROUND: Policy instruments based on the working of markets have been
      introduced to empower consumers of healthcare. However, it is still not easy to
      become a critical consumer of healthcare. OBJECTIVES: The aim of this study is to
      analyse the possibilities of the state to strengthen the position of patients
      with the aid of a new financial regime, such as personal health budgets. METHODS:
      Data were collected through in-depth interviews with executives, managers,
      professionals and client representatives of six long-term care institutions.
      RESULTS: With the introduction of individual budgets the responsibility for
      budgetary control has shifted from the organisational level to the individual
      level in the caregiver-client relationship. Having more luxurious care on offer
      necessitates a stronger demarcation of regular care because organisations cannot
      simultaneously offer extra care as part of the standard care package. New
      financial instruments have an impact on the culture of receiving and giving care.
      Distributive justice takes on new meaning with the introduction of financial
      market mechanisms in healthcare; the distributing principle of 'need' is
      transformed into the principle of 'economic demand'. CONCLUSION: Financial
      instruments not only act as a countervailing power against providers
      insufficiently client-oriented, but are also used by providers to reinforce their
      own positions vis-a-vis demanding clients. Tailor-made finance is not the same as
      tailor-made care.

PMID- 20133401
TI  - Normative consent and opt-out organ donation.
AB  - One way of increasing the supply of organs available for transplant would be to
      switch to an opt-out system of donor registration. This is typically assumed to
      operate on the basis of presumed consent, but this faces the objection that not
      all of those who fail to opt out would actually consent to the use of their
      cadaveric organs. This paper defuses this objection, arguing that people's
      actual, explicit or implicit, consent to use their organs is not needed. It
      borrows David Estlund's notion of 'normative consent' from the justification of
      political authority and applies it to the case of organ donation. According to
      this idea, when it is wrong to withhold consent to something, the moral force of
      that lack of consent may be null and void. If it is wrong of a person to refuse
      to donate their cadaveric organs to others, then it may be that their actual
      consent is not needed. This supports an opt-out system, which provides protection
      for those who have genuine reasons to refuse donation, and spares the worries as
      to what the deceased would actually have wanted.

PMID- 20133402
TI  - Are patients receiving enough information about healthcare rationing? A
      qualitative study.
AB  - BACKGROUND: There is broad international agreement from clinicians and academics
      that healthcare rationing should be undertaken as explicitly as possible, and the
      BMA have publicly supported the call for more accountable priority setting for
      some time. However, studies in the UK and elsewhere suggest that clinicians
      experience a number of barriers to rationing openly, and the information needs of
      patients at the point of provision are largely unknown. METHODOLOGY: In-depth
      interviews were undertaken with NHS professionals working at the community level
      of provision, and with patients and professionals receiving or providing
      treatment for morbid obesity and breast cancer (n=52). RESULTS: Nearly all
      patients wanted to know about healthcare rationing and had high expectations of
      their clinical professionals to provide all relevant information about treatment
      options. However, professionals did not always understand these information
      requirements, and cases of implicit rationing were common. The existence of
      relevant national guidance was not always known about, meaning that patients were
      often reliant on other sources of information about treatment options, which
      included the popular media, the internet, patient advocacy groups and informal
      networks of support. DISCUSSION: Clinical professionals need to understand
      patients' need for detailed information when it comes to rationing, and to
      understand that they are the main gateway for this to be provided. However,
      disclosure could be distressing for both patients and professionals, and thus the
      most sensitive and acceptable ways to make this information available requires
      further investigation.

PMID- 20133403
TI  - Examining the public refusal to consent to DNA biobanking: empirical data from a
      Swedish population-based study.
AB  - OBJECTIVES: To investigate empirically the motivations for not consenting to DNA
      biobanking in a Swedish population-based study and to discuss the implications.
      DESIGN: Structured questionnaires and semistructured interviews. SETTING: A
      longitudinal epidemiological project (PART) ongoing since 1998 in Stockholm,
      Sweden. The DNA-collection wave took place during 2006-7. PARTICIPANTS: 903
      individuals completed the questionnaire (participation rate 36%) and 23 were
      interviewed. All individuals had participated in both non-genetic waves of the
      project, but refused to contribute saliva samples during the DNA-collection wave.
      MAIN OUTCOME MEASURES: Motivations behind refusing to consent to DNA biobanking,
      with subsequent focus on participants' explanations regarding this unwillingness.
      RESULTS: Public refusal to consent to DNA biobanking, as revealed by the
      questionnaire, was mainly explained by a lack of personal relevance of DNA
      contribution and feelings of discomfort related to the DNA being used for
      purposes other than the respective study. Interviews of individuals representing
      the second motivation, revealed a significant mistrust of DNA biobank studies.
      The underlying beliefs and attitudes were associated with concerns about
      integrity, privacy, suspiciousness and insecurity. However, most interviewees
      were supportive of genetic research per se and interpreted their mistrust in the
      light of distressing environmental influences. CONCLUSION: The results suggest a
      need for guidelines on benefit sharing, as well as trustworthy and stable
      measures to maintain privacy, as a means for increasing personal relevance and
      trust among potential participants in genetic research. Measures taken from
      biobanks seem insufficient in maintaining and increasing trust, suggesting that
      broader societal measures should be taken.

PMID- 20133404
TI  - National Bioethics Council: a Brazilian proposal.
AB  - The number of national bioethics commissions has burgeoned since the
      establishment of the first one in 1983. They provide an arena in which
      stakeholders with widely differing moral views can discuss, interact and
      negotiate about controversial matters. The establishment of the Brazilian
      committee is used as an example of how such bodies can be introduced. If such
      councils are to be implemented effectively and regarded as legitimate, the
      society as a whole should be included in the construction of the proposal and
      represented on the council, the council should have the benefit of specialist
      advice when that is needed, and the council should be linked to the elected
      government in an official advisory capacity. The article describes long process
      of planning and consultation to establish Brazil's National Bioethics Council and
      of eventually defining its task as advising the president on matters relating to
      bioethics.

PMID- 20133405
TI  - Importance of explanation before and after forensic autopsy to the bereaved
      family: lessons from a questionnaire study.
AB  - To investigate how bereaved families felt about the explanation received before
      and after forensic autopsies, the authors conducted a cross-sectional survey of
      the bereaved families whose next of kin underwent a forensic autopsy at the two
      Departments of Forensic Medicine and a few bereaved families of crime victims. Of
      403 questionnaires sent, 126 families responded. Among 81.5% of the respondents
      who received an explanation from policemen before the autopsy, 78.8% felt that
      the quality of the explanation was poor or improper. In Japan, the law has
      restricted disclosure of information from a forensic autopsy. Despite legal
      restrictions, 82% wanted to hear from the person who conducted the autopsy.
      However, police explained the results of autopsy to 65.2% of respondents. Among
      the families whose frustration and anger increased after autopsy, 86.4% had not
      been satisfied with the explanation before the autopsy. Additionally, 57.7% had
      not been informed on the autopsy findings at the time of the questionnaire when
      more than 2 years had passed after the autopsy. These results reminded us of the
      importance of an explanation before and shortly after a forensic autopsy for a
      better understanding and acceptance by bereaved families.

PMID- 20133406
TI  - Assessment of parental decision-making in neonatal cardiac research: a pilot
      study.
AB  - OBJECTIVE: To assess parental permission for a neonate's research participation
      using the MacArthur competence assessment tool for clinical research (MacCAT-CR),
      specifically testing the components of understanding, appreciation, reasoning and
      choice. STUDY DESIGN: Quantitative interviews using study-specific MacCAT-CR
      tools. HYPOTHESIS: Parents of critically ill newborns would produce comparable
      MacCAT-CR scores to healthy adult controls despite the emotional stress of an
      infant with critical heart disease or the urgency of surgery. Parents of infants
      diagnosed prenatally would have higher MacCAT-CR scores than parents of infants
      diagnosed postnatally. There would be no difference in MacCAT-CR scores between
      parents with respect to gender or whether they did or did not permit research
      participation. PARTICIPANTS: Parents of neonates undergoing cardiac surgery who
      had made decisions about research participation before their neonate's surgery.
      METHODS: The MacCAT-CR. RESULTS: 35 parents (18 mothers; 17 fathers) of 24
      neonates completed 55 interviews for one or more of three studies. Total scores:
      magnetic resonance imaging (mean 36.6, SD 7.71), genetics (mean 38.8, SD 3.44),
      heart rate variability (mean 37.7, SD 3.30). Parents generally scored higher than
      published subject populations and were comparable to published control
      populations with some exceptions. CONCLUSIONS: The MacCAT-CR can be used to
      assess parental permission for neonatal research participation. Despite the
      stress of a critically ill neonate requiring surgery, parents were able to
      understand study-specific information and make informed decisions to permit their
      neonate's participation.

PMID- 20133407
TI  - Hidden risks associated with clinical trials in developing countries.
AB  - The academic literature in research ethics has been marked in the past decade by
      a much broader focus on the need for the protection of developing communities
      subjected to international clinical trials. Because of the proximity of the
      revision of the Declaration of Helsinki, completed in October 2008, most papers
      have addressed the issue of a double standard of care following the use of
      placebo. However, other no less important issues, such as interactions between
      the lifestyles structures of low-income communities and the efficiency of risk
      minimising procedures also deserve attention. The purpose of this paper is to
      discuss forms of uncertainty involved in clinical trials in poor and low-income
      countries that are not addressed by conventional methods of risk assessment.
      Furthermore, the increase in size of risks that are identified by conventional
      assessment methods will be addressed. Besides, the difficulty in properly
      applying risk-minimising procedures will be discussed. Finally, this paper
      proposes the involvement of research ethics committees in the risk evaluation
      process and the establishment of national ethics evaluation systems.

PMID- 20133408
TI  - The use of placebo in a trial of rectal artesunate as initial treatment for
      severe malaria patients en route to referral clinics: ethical issues.
AB  - Placebo-controlled trials are controversial when individuals might be denied
      existing beneficial medical interventions. In the case of malaria, most patients
      die in rural villages without healthcare facilities. An artesunate suppository
      that can be given by minimally skilled persons might be of value when patients
      suddenly become too ill for oral treatment but are several hours from a facility
      that can give injectable treatment for severe disease. In such situations, by
      default, no treatment is (or can be) given until the patient reaches a facility,
      making the placebo control design clinically relevant; alternative bioequivalence
      designs at the facility would misrepresent reality and risk incorrect
      conclusions. We describe the ethical issues underpinning a placebo-controlled
      trial in severe malaria. To protect patients and minimise risk, all patients were
      referred immediately to hospital so that each had a higher chance of prompt
      treatment through participation. There was no difference between artesunate and
      placebo in patients who reached clinic rapidly; among those who could not, a
      single artesunate suppository significantly reduced death or permanent
      disability, a finding of direct and indirect benefit to patients in participating
      villages and elsewhere.

PMID- 20133409
TI  - Attributes of a good physician: what are the opinions of first-year medical
      students?
AB  - BACKGROUND: Undergraduate medical education is beginning to concern itself with
      educating students about professional attributes as well as about clinical
      knowledge and skills. Defining these characteristics, and in particular seeking
      the help of the students themselves to define them, can be a useful starting
      point when considering how to incorporate aspects of professional behaviour into
      the medical curricula. METHOD: This study explores the views of first-year
      medical students at Kocaeli University Faculty of Medicine in the 2007-8 academic
      year. The students were asked the open-ended question: 'What, in your opinion,
      are the attributes a good physician should have?' Four topics were defined by
      researchers based on the undergraduate and graduate education projects. The
      attributes expressed by the students were evaluated by the researchers according
      to these topics and compared with the topics covered in the undergraduate and
      graduate education projects. RESULTS: A total of 127 students responded, and
      between them suggested 756 attributes. The majority of these attributes (54.6%)
      were concerned with interpersonal relations and communication, whereas the
      category representing the fewest attributes (12.3%) was that involving scientific
      knowledge and medical practice. In general, students' perception corresponded to
      the concept of the 'competent physician' as described in the professionalism
      projects, but attributes reflecting their world-view were also expressed.
      CONCLUSION: Experience suggests that the active participation of students in
      determining which attributes are necessary for a good physician is a positive way
      of ensuring they embrace the importance of such qualities and attributes in
      themselves.

PMID- 20133410
TI  - Post-recruitment confirmation of informed consent by SMS.
AB  - BACKGROUND: To allow patients to reflect about a decision to participate in a
      clinical trial, guidelines suggest a 24-h delay from when they are informed about
      the trial to when they give consent. In certain clinical settings, this is likely
      to hamper recruitment. METHOD: After oral and written information about the trial
      has been given in person, the patient signs the declaration of consent knowing
      that they will be asked again after 24 h whether they confirm or regret the
      decision. This procedure can be done by SMS. The investigators must document the
      response. The procedure was tried in a study in which the doctors were randomly
      assigned to receive a clinical communication skills course, and encounters with
      patients were videotaped before and after the course. RESULTS: 553 patients were
      approached, 530 (95.8%) gave initial consent, eight of these later regretted
      their consent. DISCUSSION: The low level of regrets suggests this is an
      acceptable procedure for patients. TRIAL REGISTRATION: The RCT was registered
      before initiation - registration # ISRCTN22153332.

PMID- 20133411
TI  - Mycobacterium marinum infection complicated by anti-tumour necrosis factor
      therapy.
AB  - Mycobacteria other than tuberculosis infections in patients taking various tumour
      necrosis factor (TNF)-alpha inhibitors have been reported in the literature. We
      describe sporotrichoid spread of Mycobacterium marinum in a man with Crohn's
      disease treated with infliximab. After starting ethambutol and rifampicin and
      discontinuing infliximab, a worsening appeared. M. marinum infection may have a
      potential local spread and systemic dissemination in patients treated with TNF
      alpha inhibitors.

PMID- 20133412
TI  - Protein-losing enteropathy and hypogammaglobulinaemia as first manifestations of
      disseminated histoplasmosis coincident with Nocardia infection.
AB  - Disseminated histoplasmosis and nocardiosis typically affect immunocompromised
      hosts. We report a case of gastrointestinal and adrenal histoplasmosis,
      presenting as protein-losing enteropathy and hypogammaglobulinaemia, coincident
      with Nocardia infection, in a HIV-negative patient in whom a specific
      immunological defect could not be identified. Clinicians in areas of non
      endemicity should be vigilant for rare manifestations of histoplasmosis.

PMID- 20133413
TI  - Typing of Clostridium difficile isolates endemic in Japan by sequencing of slpA
      and its application to direct typing.
AB  - A typing system for Clostridium difficile using sequencing of the surface-layer
      protein A encoding gene (slpA) was evaluated and used to analyse clinical
      isolates in Japan. A total of 160 stool specimens from symptomatic patients in
      Japan was examined and 87 C. difficile isolates were recovered. slpA sequence
      typing was found to have reliable typability and discriminatory power in
      comparison with PCR ribotyping, and the typing results were highly reproducible
      and comparable. slpA sequence typing was used to type C. difficile in DNA
      extracted directly from stool specimens. Among the 90 stool specimens in which
      direct typing results were obtained, 77 specimens were positive for C. difficile
      culture, and typing results from isolated strains agreed with those from direct
      typing in all 77 specimens. The slpA sequence type smz was dominant at all four
      hospitals examined, and this endemic type was detected by culture and/or direct
      typing in 61 (62 %) of 99 stool specimens positive for toxic culture and/or
      direct slpA sequence typing. Comparison of epidemic strains reported throughout
      the world revealed one isolate identified as slpA sequence type gc8, which was
      found to correspond to PCR ribotype 027 (BI/NAP1/027), whereas no isolates were
      found with the slpA gene identical to that of PCR ribotype 078 strain. slpA
      sequence typing is valuable for comparison of C. difficile strains epidemic in
      diverse areas because the typing results are reproducible and can easily be
      shared. In addition, slpA sequence typing could be applied to direct typing
      without culture.

PMID- 20133414
TI  - Detection of Mycobacterium tuberculosis from paraffin-embedded tissues by INNO
      LiPA Rif.TB assay: retrospective analyses of Health Protection Agency National
      Mycobacterium Reference Laboratory data.
AB  - Molecular diagnostic methods are of potential value in identifying tuberculosis
      (TB) and drug resistance where tissue specimens have been submitted for histology
      but not for microbiological culture. All paraffin-embedded tissue (PET) specimens
      (n=60) referred to a single national centre over a 42 month study period were
      analysed using the INNO-LiPA Rif.TB assay; 29/60 patients had been reported to
      the UK Enhanced Tuberculosis Surveillance database with a diagnosis of TB based
      on clinical, radiological and histological evidence. Mycobacterium tuberculosis
      (MTB) DNA was detectable in 5 out of 29 reported TB cases (17.2 %); 12 out of 29
      of the reported TB cases had a positive MTB culture from a secondary clinical
      specimen and MTB DNA was detectable in 2 of the 12 (16.7 %) laboratory-confirmed
      TB cases. Referring clinicians should be aware of the limitations of this assay
      on PETs, and should request molecular testing only in patients with a high
      clinical probability of TB and when acid-fast bacilli are seen in tissue
      specimens.

PMID- 20133415
TI  - Empyema due to a highly transmissible Pseudomonas aeruginosa strain in an adult
      cystic fibrosis patient.
AB  - Chronic pulmonary infection with Pseudomonas aeruginosa occurs in up to 85 % of
      individuals with cystic fibrosis (CF) by the time they reach adulthood, and is
      the major cause of morbidity and mortality: nearly all patients die from
      progressive respiratory failure due to repeated pulmonary exacerbations. However,
      despite the predilection of this organism for the lungs of CF people, infection
      of the pleura is much less common and is not well described in the CF population.
      We describe what is believed to be the first case of pleural empyema due to a
      particularly pathogenic transmissible strain of P. aeruginosa (the Liverpool
      epidemic strain) in an adult CF patient.

PMID- 20133416
TI  - Endocarditis caused by Lactobacillus jensenii in an immunocompetent patient.
AB  - Lactobacilli are Gram-positive rod-shaped bacteria that inhabit the oral cavity,
      gastrointestinal tract, vagina and nasal cavity. In this report, a rare case of
      Lactobacillus jensenii endocarditis in a 47-year-old immunocompetent patient is
      described. Blood cultures and a replaced mitral valve were positive for L.
      jensenii as assessed by 16S rRNA gene sequencing. Based on susceptibility tests
      the patient was successfully treated with a mixture of teicoplanin and meropenem
      antimicrobial therapy.

PMID- 20133418
TI  - Aetiology of sudden cardiac death in athletes in the UK.

PMID- 20133420
TI  - A case of sudden cardiac arrest: is it truly idiopathic?

PMID- 20133421
TI  - The additive value of biomarkers to clinical risk scores in acute coronary
      syndrome. Are biomarkers really ready for real world usage?

PMID- 20133423
TI  - Hypoplastic left heart syndrome.

PMID- 20133424
TI  - Cardiovascular magnetic resonance imaging in patients with acute myocardial
      infarction.

PMID- 20133425
TI  - Membranous interventricular septal aneurysm resulted in complete atrioventricular
      block.

PMID- 20133426
TI  - Appearance of a double aortic arch in DiGeorge syndrome on ECG-gated 64 detector
      row computed tomography.

PMID- 20133427
TI  - Not just alternating ectopics.

PMID- 20133428
TI  - Heavy metals zinc, cadmium, and copper stimulate pulmonary sensory neurons via
      direct activation of TRPA1.
AB  - Airway exposure to zinc dust and zinc-containing ambient particulates can cause
      symptoms of airway irritation and inflammation, but the underlying molecular and
      cellular mechanisms are largely unknown. Transient receptor potential A1 (TRPA1)
      is selectively expressed in a subpopulation of pulmonary C-fiber afferents and
      has been considered as a major irritant sensor in the lung and airways. Using
      whole cell patch-clamp recording and Ca(2+) imaging, we have demonstrated that
      application of ZnCl(2) concentration dependently evoked inward current and Ca(2+)
      transient in isolated vagal pulmonary sensory neurons; both responses were almost
      completely inhibited after pretreatment with AP18, a specific TRPA1 antagonist.
      In anesthetized spontaneously breathing animals, intratracheal instillation of
      ZnCl(2) (2 mM, 25 microl) induced pronounced respiratory depression in wild-type
      mice, and the effect was essentially absent in TRPA1-deficient mice. In addition,
      our study showed that two other heavy metals, cadmium and copper, also stimulated
      pulmonary sensory neurons via a direct activation of TRPA1. In summary, our
      results suggest that activation of TRPA1 in pulmonary C-fiber sensory nerves may
      contribute to the respiratory toxicity induced by airway exposure to these three
      heavy metals.

PMID- 20133429
TI  - The insulin-like growth factor (IGF)-I E-peptides are required for isoform
      specific gene expression and muscle hypertrophy after local IGF-I production.
AB  - Insulin-like growth factor I (IGF-I) coordinates proliferation and
      differentiation in a wide variety of cell types. The igf1 gene not only produces
      IGF-I, but also generates multiple carboxy-terminal extensions, the E-peptides,
      through alternative splicing leading to different isoforms. It is not known if
      the IGF-I isoforms share a common pathway for their actions, or if there are
      specific actions of each protein. Viral administration of murine IGF-IA, IGF-IB,
      and mature IGF, which lacked an E-peptide extension, was utilized to identify IGF
      I isoform-specific responsive genes in muscles of young growing mice. Microarray
      analysis revealed responses that were driven by increased IGF-I regardless of the
      presence of E-peptide, such as Bcl-XL. In contrast, distinct expression patterns
      were observed after viral delivery of IGF-IA or IGF-IB, which included matrix
      metalloproteinase 13 (MMP13). Expression of Bcl-XL was prevented when viral
      administration of the IGF-I isoforms was performed into muscles of MKR mice,
      which lack functional IGF-I receptors on the muscle fibers. However, MMP13
      expression persisted under the same conditions after viral injection of IGF-IB.
      At 4 mo after viral delivery, expression of IGF-IA or IGF-IB promoted muscle
      hypertrophy, but viral delivery of mature IGF-I failed to increase muscle mass.
      These studies provide evidence that local production of IGF-I requires the E
      peptides to drive hypertrophy in growing muscle and that both common and unique
      pathways exist for the IGF-I isoforms to promote biological effects.

PMID- 20133430
TI  - Using molecular classification to predict gains in maximal aerobic capacity
      following endurance exercise training in humans.
AB  - A low maximal oxygen consumption (VO2max) is a strong risk factor for premature
      mortality. Supervised endurance exercise training increases VO2max with a very
      wide range of effectiveness in humans. Discovering the DNA variants that
      contribute to this heterogeneity typically requires substantial sample sizes. In
      the present study, we first use RNA expression profiling to produce a molecular
      classifier that predicts VO2max training response. We then hypothesized that the
      classifier genes would harbor DNA variants that contributed to the heterogeneous
      VO2max response. Two independent preintervention RNA expression data sets were
      generated (n=41 gene chips) from subjects that underwent supervised endurance
      training: one identified and the second blindly validated an RNA expression
      signature that predicted change in VO2max ("predictor" genes). The HERITAGE
      Family Study (n=473) was used for genotyping. We discovered a 29-RNA signature
      that predicted VO2max training response on a continuous scale; these genes
      contained approximately 6 new single-nucleotide polymorphisms associated with
      gains in VO2max in the HERITAGE Family Study. Three of four novel candidate genes
      from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e.,
      "reciprocal" RNA validation of a quantitative trait locus genotype), enhancing
      the performance of the 29-RNA-based predictor. Notably, RNA abundance for the
      predictor genes was unchanged by exercise training, supporting the idea that
      expression was preset by genetic variation. Regression analysis yielded a model
      where 11 single-nucleotide polymorphisms explained 23% of the variance in gains
      in VO2max, corresponding to approximately 50% of the estimated genetic variance
      for VO2max. In conclusion, combining RNA profiling with single-gene DNA marker
      association analysis yields a strongly validated molecular predictor with
      meaningful explanatory power. VO2max responses to endurance training can be
      predicted by measuring a approximately 30-gene RNA expression signature in muscle
      prior to training. The general approach taken could accelerate the discovery of
      genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of
      physiological and pharmacological phenotypes in humans.

PMID- 20133431
TI  - A high-fat diet increases risk of ventricular arrhythmia in female rats: enhanced
      arrhythmic risk in the absence of obesity or hyperlipidemia.
AB  - Obesity increases the incidence of cardiac arrhythmias and impairs wound healing.
      However, it is presently unknown whether a high-fat diet affects arrhythmic risk
      or wound healing before the onset of overt obesity or hyperlipidemia. After 8 wk
      of feeding a high-fat diet to adult female rats, a nonsignificant increase in
      body weight was observed and associated with a normal plasma lipid profile.
      Following ischemia/reperfusion injury, scar length (standard diet 0.29 +/- 0.09
      vs. high-fat 0.32 +/- 0.13 cm), thickness (standard diet 0.047 +/- 0.02 vs. high
      fat 0.059 +/- 0.01 cm), and collagen alpha(1) type 1 content (standard diet 0.21
      +/- 0.04 vs. high-fat 0.20 +/- 0.04 arbitrary units/mm(2)) of infarcted hearts
      were not altered by the high-fat diet. However, the mortality rate was greatly
      increased 24 h postinfarction (from 5% to 46%, P < 0.01 for ischemia/reperfusion
      rats; from 20% to 89%, P < 0.0001, in complete-occlusion rats) in high-fat fed
      rats, in association with a higher prevalence of ventricular arrhythmias.
      Ventricular arrhythmia inducibility was also significantly increased in
      noninfarcted rats fed a high-fat diet. In the hearts of rats fed a high-fat diet,
      connexin-40 expression was absent, connexin-43 was hypophosphorylated and
      lateralized, and neurofilament-M immunoreactive fiber density (standard diet
      2,020 +/- 260 vs. high-fat diet 2,830 +/- 250 microm(2)/mm(2)) and tyrosine
      hydroxylase protein expression were increased (P < 0.05). Thus, in the absence of
      overt obesity and hyperlipidemia, sympathetic hyperinnervation and an aberrant
      pattern of gap junctional protein expression and regulation in the heart of
      female rats fed a high-fat diet may have contributed in part to the higher
      incidence of inducible cardiac arrhythmias.

PMID- 20133432
TI  - The role of medullary serotonin (5-HT) neurons in respiratory control:
      contributions to eupneic ventilation, CO2 chemoreception, and thermoregulation.
AB  - The functional roles of the medullary raphe, and specifically 5-HT neurons, are
      not well understood. It has previously been stated that the role of 5-HT has been
      so difficult to understand, because "it is implicated in virtually everything,
      but responsible for nothing"(Cowen PJ. Foreword. In: Serotonin and Sleep:
      Molecular, Functional and Clinical Aspects, edited by Monti JM, Prandi-Perumal
      SR, Jacobs BL, Nutt DJ. Switzerland: Birkhauser, 2008). Are 5-HT neurons
      important, and can we assign a general, or even specific, function to them given
      their diffuse projections? Recent data obtained from transgenic animals and other
      model systems indicate that the 5-HT system is not expendable, particularly
      during postnatal development, and likely plays specific roles in vital functions
      such as respiratory and thermoregulatory control. We recently provided a detailed
      and updated review of one specific function of 5-HT neurons, as central
      respiratory chemoreceptors contributing to the brain's ability to detect changes
      in pH/CO2 and stimulate adjustments to ventilation accordingly (9). Here, we turn
      our focus to recent data demonstrating that 5-HT neurons provide an essential
      excitatory drive to the respiratory network. We then further discuss their role
      in the CO2 chemoreflex, as well as other homeostatic functions that are closely
      related to ventilatory control. Last, we provide additional hypotheses/concepts
      that are worthy of further study, and how 5-HT neurons may be involved in human
      disease.

PMID- 20133433
TI  - Central chemoreception in wakefulness and sleep: evidence for a distributed
      network and a role for orexin.
AB  - This minireview examines data showing the locations of central chemoreceptor
      sites as identified by the presence of ventilatory responses to focal, mild
      acidification produced in unanesthetized animals in vivo, how the site-specific
      responses vary by arousal state, and what the emerging role of orexin might be in
      this state-dependent central chemoreceptor system. We comment on the organization
      of this distributed central chemoreceptor system and suggest that interactions
      among sites are synergistic and not additive, which is an important aspect of its
      normal function.

PMID- 20133434
TI  - Disruption of BCAA metabolism in mice impairs exercise metabolism and endurance.
AB  - Exercise enhances branched-chain amino acid (BCAA) catabolism, and BCAA
      supplementation influences exercise metabolism. However, it remains controversial
      whether BCAA supplementation improves exercise endurance, and unknown whether the
      exercise endurance effect of BCAA supplementation requires catabolism of these
      amino acids. Therefore, we examined exercise capacity and intermediary metabolism
      in skeletal muscle of knockout (KO) mice of mitochondrial branched-chain
      aminotransferase (BCATm), which catalyzes the first step of BCAA catabolism. We
      found that BCATm KO mice were exercise intolerant with markedly decreased
      endurance to exhaustion. Their plasma lactate and lactate-to-pyruvate ratio in
      skeletal muscle during exercise and lactate release from hindlimb perfused with
      high concentrations of insulin and glucose were significantly higher in KO than
      wild-type (WT) mice. Plasma and muscle ammonia concentrations were also markedly
      higher in KO than WT mice during a brief bout of exercise. BCATm KO mice
      exhibited 43-79% declines in the muscle concentration of alanine, glutamine,
      aspartate, and glutamate at rest and during exercise. In response to exercise,
      the increments in muscle malate and alpha-ketoglutarate were greater in KO than
      WT mice. While muscle ATP concentration tended to be lower, muscle IMP
      concentration was sevenfold higher in KO compared with WT mice after a brief bout
      of exercise, suggesting elevated ammonia in KO is derived from the purine
      nucleotide cycle. These data suggest that disruption of BCAA transamination
      causes impaired malate/aspartate shuttle, thereby resulting in decreased alanine
      and glutamine formation, as well as increases in lactate-to-pyruvate ratio and
      ammonia in skeletal muscle. Thus BCAA metabolism may regulate exercise capacity
      in mice.

PMID- 20133435
TI  - Mechanism of platelet functional changes and effects of anti-platelet agents on
      in vivo hemostasis under different gravity conditions.
AB  - Serious thrombotic and hemorrhagic problems or even fatalities evoked by either
      microgravity or hypergravity occur commonly in the world. We recently reported
      that platelet functions are inhibited in microgravity environments and activated
      under high-G conditions, which reveals the pathogenesis for gravity change
      related hemorrhagic and thrombotic diseases. However, the mechanisms of platelet
      functional variations under different gravity conditions remain unclear. In this
      study we show that the amount of filamin A coimmunoprecipitated with GPIbalpha
      was enhanced in platelets exposed to modeled microgravity and, in contrast, was
      reduced in 8 G-exposed platelets. Hypergravity induced actin filament formation
      and redistribution, whereas actin filaments were reduced in platelets treated
      with modeled microgravity. Furthermore, intracellular Ca2+ levels were elevated
      by hypergravity. Pretreatment of platelets with the cell-permeable Ca2+ chelator
      BAPTA-AM had no effect on cytoskeleton reorganization induced by hypergravity but
      significantly reduced platelet aggregation induced by ristocetin/hypergravity.
      Two anti-platelet agents, aspirin and tirofiban, effectively reversed the
      shortened tail bleeding time and reduced the death rate of mice exposed to
      hypergravity. Furthermore, the increased P-selectin surface expression was
      obviously reduced in platelets from mice treated with aspirin/hypergravity
      compared with those from mice treated with hypergravity alone. These data suggest
      that the actin cytoskeleton reorganization and intracellular Ca2+ level play key
      roles in the regulation of platelet functions in different gravitational
      environments. The results with anti-platelet agents not only further confirm the
      activation of platelets in vivo but also suggest a therapeutic potential for
      hypergravity-induced thrombotic diseases.

PMID- 20133436
TI  - Why has reversal of the actin-myosin cross-bridge cycle not been observed
      experimentally?
AB  - We trace the history of attempts to determine whether the experimentally observed
      diminution of metabolic energy expenditure when muscles lengthen during active
      contraction is consistent with reversibility of biochemical reactions and, in
      particular, with the regeneration of ATP. We note that this scientific endeavor
      has something of a parallel flavor to it, with both early and more recent
      experiments exploiting both isolated muscle preparations and exercising human
      subjects. In tracing this history from the late 19th century to the present, it
      becomes clear that energy can be (at least transiently) stored in a muscle
      undergoing an eccentric contraction but that this is unlikely to be due to the
      regeneration of ATP. A recently developed, thermodynamically constrained model of
      the cross-bridge cycle provides additional insight into this conclusion.

PMID- 20133437
TI  - Lactic acidosis in vivo: testing the link between lactate generation and H+
      accumulation in ischemic mouse muscle.
AB  - The link between lactate generation and cellular acidosis has been questioned
      based on the possibility of H+ generation, independent of lactate production
      during glycolysis under physiological conditions. Here we test whether glycolytic
      H+ generation matches lactate production over a physiological pH and lactate
      range using ischemia applied to the hindlimb of a mouse. We measured the H+
      generation and ATP level in vivo using 31P-magnetic resonance spectroscopy and
      chemically determined intracellular lactate level in the hindlimb muscles. No
      significant change was found in ATP content by chemical analysis (P>0.1), in
      agreement with the stoichiometric decline in phosphocreatine (20.2+/-1.2 mM) vs.
      rise in Pi (18.7+/-2.0 mM), as measured by 31P-magnetic resonance spectroscopy. A
      substantial drop in pH from 7.0 to 6.7 and lactate accumulation to 25 mM were
      found during 25 min of ischemia. The rise in H+ generation closely agreed with
      the accumulation of lactate, as shown by a close correlation with a slope near
      identity (0.98; r2=0.86). This agreement between glycolytic H+ production and
      elevation of lactate is confirmed by an analysis of the underlying reactions
      involved in glycolysis in vivo and supports the concept of lactic acidosis under
      conditions that substantially elevate lactate and drop pH. However, this link is
      expected to fail with conditions that deplete phosphocreatine, leading to net ATP
      hydrolysis and nonglycolytic H+ generation. Thus both direct measurements and an
      analysis of the stoichiometry of glycolysis in vivo support lactate acidosis as a
      robust concept for physiological conditions of the muscle cell.

PMID- 20133438
TI  - Modulation of intracellular calcium transient in response to beta-adrenoceptor
      stimulation in the hearts of 4-wk-old rats during simulated weightlessness.
AB  - Modulation of intracellular calcium ([Ca(2+)](i)) transient in response to beta
      adrenoceptor stimulation in the hearts of hindlimb unweighted (HLU) rats during
      simulated weightlessness has not been reported. In the present study, we adopted
      the rat tail suspension for 4 wk to simulate weightlessness. Effects of simulated
      microgravity on beta-adrenoceptor responsiveness were then studied. Mean arterial
      blood pressure, left ventricular pressure (LVP), systolic function [maximum
      positive change in pressure over time (+dP/dt(max))], and diastolic function
      [maximum negative change in pressure over time (-dP/dt(max))] were monitored
      during the in vivo experiment. beta-Adrenoceptor density was quantitated by
      radioactive ligand binding. Single rat ventricular myocyte was obtained by
      enzymatic dissociation method. +/-dP/dt(max), myocyte contraction, intracellular
      [Ca(2+)](i) transient, and L-type calcium current in response to beta
      adrenoceptor stimulation with isoproterenol were measured. Compared with the
      control group, no significant changes were found in heart weight, body weight,
      and mean arterial blood pressure, whereas LVP and +/-dP/dt(max) were
      significantly reduced. LVP and +/-dP/dt(max) were significantly attenuated in the
      HLU group in response to isoproterenol administration. In the in vitro study, the
      beta-adrenoceptor density was unchanged. Effects of isoproterenol on electrically
      induced single-cell contraction and [Ca(2+)](i) transient in myocytes of
      ventricles in HLU rats were significantly attenuated. The enhanced L-type Ca(2+)
      current elicited by isoproterenol in cardiomyocytes was significantly decreased
      in the HLU group. The above results indicate that impaired function of L-type
      Ca(2+) current and decreased [Ca(2+)](i) transient cause the depressed
      responsiveness of the beta-adrenoceptor stimulation, which may be partially
      responsible for the depression of cardiac function.

PMID- 20133439
TI  - Effect of 2-wk intensified training and inactivity on muscle Na+-K+ pump
      expression, phospholemman (FXYD1) phosphorylation, and performance in soccer
      players.
AB  - The present study examined muscle adaptations and alterations in performance of
      highly trained soccer players with intensified training or training cessation.
      Eighteen elite soccer players were, for a 2-wk period, assigned to either a group
      that performed high-intensity training with a reduction in the amount of training
      (HI, n = 7), or an inactivity group without training (IN, n = 11). HI improved (P
      < 0.05) performance of the 4th, 6th, and 10th sprint in a repeated 20-m sprint
      test, and IN reduced (P < 0.05) performance in the 5th to the 10th sprints after
      the 2-wk intervention period. In addition, the Yo-Yo intermittent recovery level
      2 test performance of IN was lowered from 845 +/- 48 to 654 +/- 30 m. In HI, the
      protein expression of the Na(+)-K(+) pump alpha(2)-isoform was 15% higher (P <
      0.05) after the intervention period, whereas no changes were observed in alpha(1)
      and beta(1)-isoform expression. In IN, Na(+)-K(+) pump expression was not
      changed. In HI, the FXYD1ser68-to-FXYD1 ratio was 27% higher (P < 0.01) after the
      intervention period, and, in IN, the AB_FXYD1ser68 signal was 18% lower (P <
      0.05) after inactivity. The change in FXYD1ser68-to-FXYD1 ratio was correlated
      (r(2) = 0.35; P < 0.05) with change in performance in repeated sprint test. The
      present data suggest that short-term intensified training, even for trained
      soccer players, can increase muscle Na(+)-K(+) pump alpha(2)-isoform expression,
      and that cessation of training for 2 wk does not affect the expression of Na(+)
      K(+) pump isoforms. Resting phosphorylation status of the Na(+)-K(+) pump is
      changed by training and inactivity and may play a role in performance during
      repeated, intense exercise.

PMID- 20133440
TI  - Proximal tibia volumetric bone mineral density is correlated to the magnitude of
      local acceleration in male long-distance runners.
AB  - The beneficial effect of physical exercise on bone mineral density (BMD) is at
      least partly explained by the forces exerted directly on the bones. Male runners
      present generally higher BMD than sedentary individuals. We postulated that the
      proximal tibia BMD is related to the running distance, as well as to the
      magnitude of the shocks (while running) in male runners. A prospective study
      (three yearly measurements) included 81 healthy male subjects: 16 sedentary lean
      subjects, and 3 groups of runners (5-30 km/wk, n = 19; 30-50 km/wk, n = 29; 50
      100 km/wk, n = 17). Several measurements were performed at the proximal tibia
      level: volumetric BMD (vBMD) and cortical index (CI), i.e., an index of cortical
      bone thickness and peak accelerations (an index of shocks during heel strike)
      while running (measured by a three-dimensional accelerometer). A general linear
      model assessed the prediction of vBMD or CI by 1) simple effects (running
      distance, peak accelerations, time); and 2) interactions (for instance, if vBMD
      prediction by peak acceleration depends on running distance). CI and vBMD 1)
      increase with running distance to reach a plateau over 30 km/wk; and 2) are
      positively associated with peak accelerations over 30 km/wk. Running may be
      associated with high peak accelerations to have beneficial effects on BMD. More
      important strains are needed to be associated with the same increase in BMD
      during running sessions of short duration than those of long duration. CI and
      vBMD are associated with the magnitude of the shocks during heel strike in
      runners.

PMID- 20133441
TI  - Serotonergic projection from nucleus raphe pallidus to rostral ventrolateral
      medulla modulates cardiovascular reflex responses during acupuncture.
AB  - We have demonstrated that stimulation of somatic afferents during
      electroacupuncture (EA) inhibits sympathoexcitatory cardiovascular rostral
      ventrolateral medulla (rVLM) neurons and reflex responses. Furthermore, EA at P5
      P6 acupoints over the median nerve on the forelimb activate serotonin (5-HT)
      containing neurons in the nucleus raphe pallidus (NRP). The present study,
      therefore, examined the role of the NRP and its synaptic input to neurons in the
      rVLM during the modulatory influence of EA. Since serotonergic neurons in the NRP
      project to the rVLM, we hypothesized that the NRP facilitates EA inhibition of
      the cardiovascular sympathoexcitatory reflex response through activation of 5
      HT1A receptors in the rVLM. Animals were anesthetized and ventilated, and heart
      rate and blood pressure were monitored. We then inserted microinjection and
      recording electrodes in the rVLM and NRP. Application of bradykinin (10
      microg/ml) on the gallbladder every 10 min induced consistent excitatory
      cardiovascular reflex responses. Stimulation with EA at P5-P6 acupoints reduced
      the increase in blood pressure from 41+/-4 to 22+/-4 mmHg for more than 70 min.
      Inactivation of NRP with 50 nl of kainic acid (1 mM) reversed the EA-related
      inhibition of the cardiovascular reflex response. Similarly, blockade of 5-HT1A
      receptors with the antagonist WAY-100635 (1 mM, 75 nl) microinjected into the
      rVLM reversed the EA-evoked inhibition. In the absence of EA, NRP microinjection
      of dl-homocysteic acid (4 nM, 50 nl), to mimic EA, reduced the cardiovascular and
      rVLM neuronal excitatory reflex response during stimulation of the gallbladder
      and splanchnic nerve, respectively. Blockade of 5-HT1A receptors in the rVLM
      reversed the NRP dl-homocysteic acid inhibition of the cardiovascular and
      neuronal reflex responses. Thus activation of the NRP, through a mechanism
      involving serotonergic neurons and 5-HT1A receptors in the rVLM during somatic
      stimulation with EA, attenuates sympathoexcitatory cardiovascular reflexes.

PMID- 20133442
TI  - Airways hyperresponsiveness: a perspective from 15,000 ft.

PMID- 20133443
TI  - Construct validity of muscle force tests of the rotator cuff muscles: an
      electromyographic investigation.
AB  - BACKGROUND: Manual muscle tests (MMTs) are used in clinical settings to evaluate
      the function and strength (force-generating capacity) of a specific muscle in a
      position at which the muscle is believed to be most isolated from other
      synergists and antagonists. Despite frequent use of MMTs, few electromyographic
      evaluations exist to confirm the ability of MMTs to isolate rotator cuff muscles.
      OBJECTIVE: This study examined rotator cuff isolation during 29 shoulder muscle
      force tests (9 clinical and 20 generic tests). DESIGN: An experimental design was
      used in this study. PARTICIPANTS AND MEASUREMENTS: Electromyographic data were
      recorded from 4 rotator cuff muscles and 10 additional shoulder muscles of 12
      male participants. Maximal isolation ratios (mean specific rotator cuff muscle
      activation to mean activation of the other 13 recorded muscles) defined which of
      these tests most isolated the rotator cuff muscles. RESULTS: Three rotator cuff
      muscles were maximally isolated (obtained highest isolation ratios) within their
      respective clinical test groups (lateral rotator test group for the infraspinatus
      and teres minor muscles and abduction test group for the supraspinatus muscle).
      The subscapularis muscle was maximally isolated equally as effectively within the
      generic ulnar force and clinical medial rotation groups. Similarly, the
      supraspinatus and teres minor muscles were isolated equally as effectively in
      some generic test groups as they were in their respective clinical test groups.
      LIMITATIONS: Postural artifact in the wire electrodes caused exclusion of some
      channels from calculations. The grouping of muscle force tests based on test
      criteria (clinical or generic tests and muscle action) may have influenced which
      groups most isolated the muscle of interest. CONCLUSIONS: The results confirmed
      the appropriateness of 9 commonly used clinical tests for isolating rotator cuff
      muscles, but suggested that several other muscle force tests were equally
      appropriate for isolating these muscles.

PMID- 20133444
TI  - Muscle activation and perceived loading during rehabilitation exercises:
      comparison of dumbbells and elastic resistance.
AB  - BACKGROUND: High-intensity resistance training plays an essential role in the
      prevention and rehabilitation of musculoskeletal injuries and disorders. Although
      resistance exercises with heavy weights yield high levels of muscle activation,
      the efficacy of more user-friendly forms of exercise needs to be examined.
      OBJECTIVE: The aim of this study was to investigate muscle activation and
      perceived loading during upper-extremity resistance exercises with dumbbells
      compared with elastic tubing. DESIGN: A single-group, repeated-measures study
      design was used. SETTING: Exercise evaluation was conducted in a laboratory
      setting. PARTICIPANTS: Sixteen female workers (aged 26-55 years) without serious
      musculoskeletal diseases and with a mean neck and shoulder pain intensity of 7.8
      on a 100-mm visual analog scale participated in the study. MEASUREMENTS:
      Electromyographic (EMG) activity was measured in 5 selected muscles during the
      exercises of lateral raise, wrist extension, and shoulder external rotation
      during graded loadings with dumbbells (2-7.5 kg) and elastic tubing (Thera-Band,
      red to silver resistance). The order of exercises and loadings was randomized for
      each individual. Electromyographic amplitude was normalized to the absolute
      maximum EMG amplitude obtained during maximal voluntary isometric contraction and
      exercise testing. Immediately after each set of exercise, the Borg CR10 scale was
      used to rate perceived loading during the exercise. RESULTS: Resistance exercise
      with dumbbells as well as elastic tubing showed increasing EMG amplitude and
      perceived loading with increasing resistance. At the individually maximal level
      of resistance for each exercise-defined as the 3 repetitions maximum-normalized
      EMG activity of the prime muscles was not significantly different between
      dumbbells (59%-87%) and elastic tubing (64%-86%). Perceived loading was
      moderately to very strongly related to normalized EMG activity (r=.59-.92).
      Limitations The results of this study apply only for exercises performed in a
      controlled manner (ie, without sudden jerks or high acceleration). CONCLUSIONS:
      Comparably high levels of muscle activation were obtained during resistance
      exercises with dumbbells and elastic tubing, indicating that therapists can
      choose either type in clinical practice. The Borg CR10 can be a useful aid in
      estimating intensity of individual rehabilitation protocols.

PMID- 20133445
TI  - Fractionated stereotactic radiotherapy in patients with acromegaly: an interim
      single-centre audit.
AB  - AIM: To evaluate the effect of fractionated stereotactic radiotherapy (FSRT) in
      acromegaly in a retrospective analysis. PATIENTS AND METHODS: Thirty-four
      patients (17 females, median 43 years (range 30-74)) with acromegaly were treated
      with FSRT (conformal dynamic arcing, dose 54 Gy, 27-30 fractions) between January
      1998 and April 2007. Of the 34 patients, 32 had undergone transsphenoidal
      adenotomy, and 28 were on medical therapy before FSRT. Patients on medical
      therapy continued this during and after the irradiation. The treatment was
      gradually decreased/withdrawn after careful assessment. RESULTS: Magnetic
      resonance scanning of the pituitary gland 34 months (median, range 11-95) after
      irradiation showed stable or reduced volume of the remaining tumour tissue in 31
      of 34 patients (91%). Seventeen patients (50%) were biochemically controlled
      (normalised nadir GH during oral glucose tolerance test and IGF1 <+2 S.D.) 30
      months after FSRT (median, range 6-60), and ten of them had true biochemical
      remission (off medical therapy) 30 months after FSRT (median, range 12-69). Of 28
      patients with one or more functioning pituitary axes before irradiation, 8 (29%)
      developed further deficit of one or two pituitary axes 48 months (median, range 6
      102) after FSRT. Of 34 patients, 20 still required medical treatment for
      acromegaly at the end of this study, mainly those with a short follow-up period
      after irradiation. CONCLUSION: The FSRT seems promising in terms of treatment of
      acromegaly. Longer follow-up is, however, needed to assess the overall efficacy
      and safety of FSRT for acromegaly.

PMID- 20133446
TI  - The impact of the CAG repeat polymorphism of the androgen receptor gene on muscle
      and adipose tissues in 20-29-year-old Danish men: Odense Androgen Study.
AB  - BACKGROUND: The number of CAG repeats (CAG(n)) within the CAG repeat polymorphism
      of the androgen receptor gene correlates inversely with the transactivation of
      the receptor. OBJECTIVE: To examine the impact of CAG(n) on muscle, fat
      distribution, and circulating androgen levels. Design, settings and participants
      Population-based, cross-sectional study of 783 Danish men aged 20-29 years.
      METHODS: Genotyping was performed in 767 men. Areas of thigh and lower trunk
      muscle (muscle(thigh) and muscle(lower trunk)), subcutaneous adipose tissues
      (SAT(thigh) and SAT(lower trunk)), and deep adipose tissues (i.m. and visceral)
      were measured in 393 men by magnetic resonance imaging (MRI). Lean body mass
      (LBM) and fat mass (FM) were measured in all men by whole body dual-energy X-ray
      absorptiometry (DEXA). The absolute areas acquired by MRI were the main outcomes.
      The absolute DEXA measurements and relative assessments of both modalities were
      considered as the secondary outcomes. Results CAG(n) (range: 10-32) correlated
      inversely with absolute muscle(thigh) (r=-0.108), absolute muscle(lower trunk)
      (r=-0.132), relative muscle(thigh) (r=-0.128), relative muscle(lower trunk) (r=
      0.126), relative LBM(lower extremity) (r=-0.108), and relative LBM(total) (r=
      0.082), and positively with relative SAT(thigh) (r=0.137), relative SAT(lower
      trunk) (r=0.188), relative FM(lower extremity) (r=0.107), and relative FM(total)
      (r=0.082). These relationships remained significant, controlling for physical
      activity, smoking, chronic disease, and age. CAG(n) did not correlate with any
      circulating androgen. CONCLUSIONS: The CAG repeat polymorphism affects body
      composition in young men: absolute muscle(thigh) and absolute muscle(lower trunk)
      increase as CAG(n) decreases. Expressed relatively, muscle areas and LBM
      increase, while SAT and FM decrease as CAG(n) decreases. The polymorphism does
      not affect deep adipose tissues or circulating androgen levels in young men.

PMID- 20133447
TI  - First report of ectopic ACTH syndrome and PTHrP-induced hypercalcemia due to a
      hepatoblastoma in a child.
AB  - CONTEXT: Only occasionally, endocrine-active tumors develop directly from hepatic
      tissue, and may lead to paraneoplastic syndromes (PNS). PNS mostly accompany
      malignancy of adulthood and are exceedingly rare in children. PATIENT: A girl
      aged 6 years and 9 months presented with a 2-month history of rapidly progressive
      weight gain, abdominal distension, and polyuria/pollakiuria accompanied by short
      episodes of abdominal pain. She showed the typical clinical features of Cushing's
      syndrome and a huge hepatic mass. An abdominal computed tomography (CT) scan
      revealed a large liver tumor. Blood glucose and serum calcium were greatly
      elevated. DESIGN AND OBJECTIVE: Case report describing the causative relationship
      of the clinical findings. METHODS: Physical examination; ultrasound of the
      abdomen; CT scan of the abdomen and the chest; conventional X-rays; routine
      hematology; blood chemistry and multiple parameters of calcium and phosphorus
      metabolism; multisteroid analysis in serum and urine; adrenocortical stimulation
      and suppression tests; histopathological assessment of the resected tumor;
      immunohistochemistry for ACTH, beta-endorphin, corticotrophin-releasing hormone
      (CRH), and PTH-related peptide (PTHrP); electron microscopy of tumor cells; ACTH
      and CRH extraction from the tumor tissue; and clinical follow-up for more than 20
      years. RESULTS: Giant hepatoblastoma (HB; approximately 1000 ml volume) of the
      right lobe of the liver with combined ectopic ACTH syndrome and PTHrP-induced
      tumor-associated hypercalcemia. Wide local excision and polychemotherapy led to
      complete reversal of the paraneoplastic phenotype. CONCLUSIONS: This is the first
      report of an endocrine-active HB causing both Cushing's syndrome and PTHrP
      related 'humoral hypercalcemia of malignancy'. This information should be added
      to the well-known beta-human chorionic gonadotropin-related paraneoplastic
      effects of HB in children.

PMID- 20133448
TI  - Deletion of IGF-I receptor (IGF-IR) in primary osteoblasts reduces GH-induced
      STAT5 signaling.
AB  - GH promotes longitudinal growth and regulates multiple cellular functions in
      humans and animals. GH signals by binding to GH receptor (GHR) to activate the
      tyrosine kinase, Janus kinase 2 (JAK2), and downstream pathways including signal
      transducer and activator of transcription 5 (STAT5), thereby regulating
      expression of genes including IGF-I. GH exerts effects both directly and via IGF
      I, which signals by activating the IGF-I receptor (IGF-IR). IGF-IR is a cell
      surface receptor that contains intrinsic tyrosine kinase activity within its
      intracellular domain. In this study, we examined the potential role of IGF-IR in
      facilitating GH-induced signal transduction, using mouse primary calvarial
      osteoblasts with Lox-P sites flanking both IGF-IR alleles. These cells respond to
      both GH and IGF-I and in vitro infection with an adenovirus that drives
      expression of Cre recombinase (Ad-Cre) dramatically reduces IGF-IR abundance
      without affecting the abundance of GHR, JAK2, STAT5, or ERK. Notably, infection
      with Ad-Cre, but not a control adenovirus, markedly inhibited acute GH-induced
      STAT5 activity (more than doubling the ED(50) and reducing the maximum activity
      by nearly 50%), while sparing GH-induced ERK activity, and markedly inhibited GH
      induced transactivation of a STAT5-dependent luciferase reporter. The effect of
      Ad-Cre on GH signaling was specific, as platelet-derived growth factor-induced
      signaling was unaffected by Ad-Cre-mediated reduction of IGF-IR. Ad-Cre-mediated
      inhibition of GH signaling was reversed by adenoviral reexpression of IGF-IR, but
      not by infection with an adenovirus that drives expression of a hemagglutination
      tagged somatostatin receptor, which drives expression of the unrelated
      somatostatin receptor, and Ad-Cre infection of nonfloxed osteoblasts did not
      affect GH signaling. Notably, infection with an adenovirus encoding a C
      terminally truncated IGF-IR that lacks the tyrosine kinase domain partially
      rescued both acute GH-induced STAT5 activity and GH-induced IGF-I gene expression
      in cells in which endogenous IGF-IR was reduced. These data, in concert with our
      earlier findings that GH induces a GHR-JAK2-IGF-IR complex, suggest a novel
      function for IGF-IR. In addition to its role as a key IGF-I signal transducer,
      this receptor may directly facilitate acute GH signaling. The implications of
      these findings are discussed.

PMID- 20133450
TI  - Haemodilution-induced profibrinolytic state is mitigated by fresh-frozen plasma:
      implications for early haemostatic intervention in massive haemorrhage.
AB  - BACKGROUND: Fibrinolysis contributes to coagulopathy after major trauma and
      surgery. We hypothesized that progressive haemodilution is responsible, at least
      in part, for increased fibrinolytic tendency of blood clot. METHODS: The study
      was performed in two parts. First, whole blood (WB) samples collected from six
      healthy, consented volunteers were diluted in vitro with either saline or fresh
      frozen plasma (FFP) to 40% and 15% of baseline. We quantified factor levels
      related to coagulation and fibrinolysis, and measured endogenous thrombin
      generation in undiluted control plasma samples and in samples diluted with saline
      or FFP. Additionally, thromboelastometry was used to assess susceptibility to
      fibrinolysis after adding tissue plasminogen activator in undiluted WB samples
      and in samples diluted with saline before and after substitution of fibrinogen or
      FFP. Secondly, as a model of in vivo haemodilution, we evaluated the same
      parameters before and after operation in nine consented patients undergoing off
      pump coronary artery bypass surgery. RESULTS: The dilution with saline caused
      dose-dependent decreases in plasma levels of coagulation and antifibrinolytic
      factors, and in thrombin generation. In FFP-supplemented samples, factor levels
      and thrombin generation were maintained within normal ranges. Fibrinolytic
      tendency was significantly higher after haemodilution with saline independent of
      fibrinogen substitution compared with FFP. Similarly, increased tendency for
      fibrinolysis was also observed in the in vivo haemodilution. CONCLUSIONS: We
      demonstrated in vitro and in vivo that progressive haemodilution decreases
      endogenous antifibrinolytic proteins including alpha(2)-antiplasmin and thrombin
      activatable fibrinolysis inhibitor, resulting in increased fibrinolytic tendency.
      Therefore, early fluid replacement therapy with FFP might be advantageous after
      massive haemorrhage.

PMID- 20133449
TI  - PPAR-gamma coactivator-1alpha regulates progesterone production in ovarian
      granulosa cells with SF-1 and LRH-1.
AB  - Previously, we demonstrated that bone marrow-derived mesenchymal stem cells
      (MSCs) differentiate into steroidogenic cells such as Leydig and adrenocortical
      cells by the introduction of steroidogenic factor-1 (SF-1) and treatment with
      cAMP. In this study, we employed the same approach to differentiate umbilical
      cord blood (UCB)-derived MSCs. Despite UCB-MSCs differentiating into
      steroidogenic cells, they exhibited characteristics of granulosa-luteal-like
      cells. We found that peroxisome proliferator-activated receptor-gamma coactivator
      1alpha (PGC-1alpha) was expressed and further induced by cAMP stimulation in UCB
      MSCs. Consistent with these results, tissue-specific expression of Pgc-1alpha was
      observed in rat ovarian granulosa cells. PGC-1alpha binds to the NR5A family [SF
      1 and liver receptor homolog-1 (LRH-1)] of proteins and markedly enhances their
      transcriptional activities. Reporter assays revealed that PGC-1alpha activated
      the promoter activities of SF-1 and LRH-1 target genes. Infection of KGN cells (a
      human cell line derived from granulosa cells) with adenoviruses expressing PGC
      1alpha resulted in the induction of steroidogenesis-related genes and stimulation
      of progesterone production. PGC-1alpha also induced SF-1 and LRH-1, with the
      latter induced to a greater extent. Knockdown of Pgc-1alpha in cultured rat
      granulosa cells resulted in attenuation of gene expression as well as
      progesterone production. Transactivation of the NR5A family by PGC-1alpha was
      repressed by Dax-1. PGC-1alpha binds to the activation function 2 domain of NR5A
      proteins via its consensus LXXLL motif. These results indicate that PGC-1alpha is
      involved in progesterone production in ovarian granulosa cells by potentiating
      transcriptional activities of the NR5A family proteins.

PMID- 20133451
TI  - 15-Deoxy-delta 12-14-prostaglandin-J2 induces hypertrophy and loss of
      contractility in human testicular peritubular cells: implications for human male
      fertility.
AB  - The wall of the seminiferous tubules contains contractile smooth-muscle-like
      peritubular cells, thought to be important for sperm transport. Impaired
      spermatogenesis in men typically involves remodeling of this wall, and we now
      found that smooth muscle cell (SMC) markers, namely myosin heavy chain (MYH11)
      and smooth muscle actin (SMA) are often lost or diminished in peritubular cells
      of testes of men with impaired spermatogenesis. This suggests reduced
      contractility of the peritubular wall, which may contribute to sub- or
      infertility. In these cases, testicular expression of cyclooxygenase-2 (COX-2)
      implies formation of prostaglandins (PGs). When screening different PGs for their
      ability to target human testicular peritubular cells (HTPCs), only a PG
      metabolite, 15-deoxy-Delta(12-14)-prostaglandin-J2 (15dPGJ2), was effective. In
      primary cultures of HTPCs, 15dPGJ2 increased cell size in a reversible manner.
      Importantly, 15dPGJ2 treatment resulted in a loss of typical differentiation
      markers for SMCs, namely MYH11, calponin, and SMA, whereas fibroblast markers
      were unchanged. Collagen gel contraction assays revealed that this loss
      correlates with a reduced ability to contract. Experiments with an antagonist
      (bisphenol A diglycidyl ether) and agonist (troglitazone) for a cognate 15dPGJ2
      receptor (i.e. peroxisome proliferator-activated receptor-gamma) indicated that
      peroxisome proliferator-activated receptor-gamma is not directly involved.
      Rather, the mode of action of 15dPGJ2 involves reactive oxygen species. The
      antioxidant N-acetylcysteine not only blocked ROS formation but also prevented
      the increase in cell size and the loss of contractility in HTPCs challenged with
      15dPGJ2. We conclude that 15dPGJ2, via reactive oxygen species, influences SMC
      phenotype and contractility of human peritubular cells and possibly is involved
      in the development of human male sub-/infertility.

PMID- 20133452
TI  - Prenatal dexamethasone programs expression of genes in liver and adipose tissue
      and increased hepatic lipid accumulation but not obesity on a high-fat diet.
AB  - The association between low birth weight and cardiovascular disease is amplified
      by the development of obesity. We explored the effects of postnatal high-fat (HF)
      feeding in dexamethasone (Dex)-programmed rats, in which prenatal glucocorticoid
      overexposure is associated with reduced birth weight and adult glucose
      intolerance. Male Wistar rats exposed to Dex or vehicle (Veh) during the last
      week of gestation were weaned onto HF or control diets for 6 months. Dex-exposed
      animals were of lower birth weight and showed catch-up growth by 7 wk. There were
      no differences in obesity or hyperinsulinaemia between Dex-HF and Veh-HF animals.
      However, Dex-HF animals had increased hepatic triglyceride content compared with
      Veh-HF animals. mRNA transcript profiles in adipose tissue revealed depot
      specific changes in the expression of genes involved in fatty acid esterification
      and triglyceride synthesis and storage with prenatal Dex exposure. Thus,
      antenatal glucocorticoid overexposure in rats does not confer increased
      sensitivity to HF diet-induced obesity, but increases susceptibility to fatty
      liver. This may be due to depot-specific-programmed alterations in fat metabolism
      in adipose tissue.

PMID- 20133453
TI  - Growth activation alone is not sufficient to cause metastatic thyroid cancer in a
      mouse model of follicular thyroid carcinoma.
AB  - TSH is the major stimulator of thyrocyte proliferation, but its role in thyroid
      carcinogenesis remains unclear. To address this question, we used a mouse model
      of follicular thyroid carcinoma (FTC) (TRbeta(PV/PV) mice). These mice, harboring
      a dominantly negative mutation (PV) of the thyroid hormone-beta receptor
      (TRbeta), exhibit increased serum thyroid hormone and elevated TSH. To eliminate
      TSH growth-stimulating effect, TRbeta(PV/PV) mice were crossed with TSH receptor
      gene knockout (TSHR(-/-)) mice. Wild-type siblings of TRbeta(PV/PV) mice were
      treated with an antithyroid agent, propylthiouracil, to elevate serum TSH for
      evaluating long-term TSH effect (WT-PTU mice). Thyroids from TRbeta(PV/PV)TSHR(-/
      ) showed impaired growth with no occurrence of FTC. Both WT-PTU and TRbeta(PV/PV)
      mice displayed enlarged thyroids, but only TRbeta(PV/PV) mice developed
      metastatic FTC. Molecular analyses indicate that PV acted, via multiple
      mechanisms, to activate the integrins-Src-focal adhesion kinase-p38 MAPK pathway
      and affect cytoskeletal restructuring to increase tumor cell migration and
      invasion. Thus, growth stimulated by TSH is a prerequisite but not sufficient for
      metastatic cancer to occur. Additional genetic alterations (such as PV), destined
      to alter focal adhesion and migration capacities, are required to empower
      hyperplastic follicular cells to invade and metastasize. These in vivo findings
      provide new insights in understanding carcinogenesis of the human thyroid.

PMID- 20133454
TI  - The levels of the endocannabinoid receptor CB2 and its ligand 2
      arachidonoylglycerol are elevated in endometrial carcinoma.
AB  - The endocannabinoid system plays protective roles against the growth and the
      spreading of several types of carcinomas. Because estrogens regulate this system
      both in physiological states and cancer, in this paper we evaluated its
      involvement in endometrial carcinoma, a well-known estrogen-dependent tumor. To
      test whether the endocannabinoid system is expressed in endometrial cancer,
      tissue samples were collected both from 18 patients undergoing surgical treatment
      for endometrial adenocarcinoma and 16 healthy age-matched controls, and treated
      for Western blot and immunohistochemical analysis. Moreover, tissues were dounce
      homogenized and submitted to endocannabinoid measurement by liquid chromatography
      mass spectrometry. To evaluate the physiological role of the endocannabinoid
      system, a human endometrial cancer cell-line (AN3CA) was used and transiently
      transfected with a plasmid containing the cDNA for the endocannabinoid receptor
      CB(2). Cells were incubated for 48 h with an agonist (JWH133) (10 mum) or
      antagonist (SR144528) (1 mum) of CB(2) 24 h after transfection, and cell
      proliferation was measured by the 3-[4,5-dimethyltiazol-2yl]-2,5
      diphenyltetrazolium bromide formazan assay. In human endometrial carcinoma
      biopsies the expression of CB(2) receptor and the levels of its ligand, 2
      arachidonoylglycerol increased, whereas monoacylglycerol lipase, an enzyme
      responsible for 2-arachidonoylglycerol degradation, was down-regulated.
      Immunohistochemical analysis revealed that CB(2) was overexpressed only in
      malignant endometrial cells. CB(2)-overexpressing AN3CA cells showed a
      significant reduction in cell vitality compared with parental AN3CA cells:
      incubation with the selective CB(2) antagonist SR144128 restored the viability of
      CB(2)-overexpressing cells to that of untransfected cells. In conclusion, the
      endocannabinoid system seems to play an important role in human endometrial
      carcinoma, and modulation of CB(2) activity/expression may account for a tumor
      suppressive effect.

PMID- 20133455
TI  - Role of estradiol in the dynamic control of tanycyte plasticity mediated by
      vascular endothelial cells in the median eminence.
AB  - In the ever-changing physiological context of the neuroendocrine brain, the
      mechanisms by which cellular events involving neurons, astroglia, and vascular
      cells are coordinated to bring forth the appropriate neuronal signaling is not
      yet known but is amenable to examination. In the median eminence of the
      hypothalamus, endothelial cells are key players in the plasticity of tanycytes
      (specialized astroglia) and neuroendocrine synapse efficacy. Here we report that
      estradiol acts on both purified endothelial cells and isolated tanycytes to
      trigger endothelial-to-glial communication that leads to a sudden and massive
      retraction of tanycyte processes. The blockade of endothelial nitric oxide
      synthase by in vitro adenoviral-mediated gene transfer of a dominant-negative
      form of endothelial nitric oxide synthase abrogates the estradiol-induced
      tanycyte plasticity mediated by endothelial cells. In parallel, increases in
      prostaglandin-E(2) (PGE(2)) due to changes in cyclooxygenase (COX)-1 and COX-2
      expression induced by the exposure of tanycytes to estradiol promote acute
      tanycyte plasticity. We also demonstrate by electron microscopy that the
      administration of PGE(2) to median eminence explants induces rapid neuroglial
      plasticity at the neurovascular junction of neurons that release GnRH (the
      neuropeptide controlling reproduction). Conversely, preventing local PGE(2)
      synthesis in the median eminence of adult female rats with the COX inhibitor
      indomethacin impairs the ovarian cycle, a process that requires a pulsatile,
      coordinated delivery of GnRH into the hypothalamo-hypophyseal portal system.
      Taken together, our findings show that estradiol controls the dialog between
      endothelial cells and astroglia to regulate neuroglial plasticity in the
      neuroendocrine brain.

PMID- 20133456
TI  - Adenosine 5'-monophosphate-activated protein kinase-mammalian target of rapamycin
      cross talk regulates brown adipocyte differentiation.
AB  - Brown adipose tissue (BAT) is considered of metabolic significance in mammalian
      physiology, because it plays an important role in regulating energy balance.
      Alterations in this tissue have been associated with obesity and type 2 diabetes.
      The molecular mechanisms modulating brown adipocyte differentiation are not fully
      understood. Using a murine brown preadipocyte cell line, primary cultures, and
      3T3-L1 cells, we analyzed the contribution of various intracellular signaling
      pathways to adipogenic and thermogenic programs. Sequential activation of p38MAPK
      and LKB1-AMPK-tuberous sclerosis complex 2 (TSC2) as well as significant
      attenuation of ERK1/2 and mammalian target of rapamycin (mTOR)-p70 S6 kinase 1
      (p70S6K1) activation was observed through the brown differentiation process. This
      study demonstrates a critical role for AMPK in controlling the mTOR-p70S6K1
      signaling cascade in brown but not in 3T3-L1 adipocytes. We observed that mTOR
      activity is essential in the first stages of differentiation. Nevertheless,
      subsequent inhibition of this cascade by AMPK activation is also necessary at
      later stages. An in vivo study showed that prolonged 5-aminoimidazole-4
      carboxamide ribonucleoside (AICAR)-induced AMPK activation increases uncoupling
      protein 1 expression and induces an accumulation of brown adipocytes in white
      adipose tissue (WAT), as revealed by immunohistology. Moreover, the induction of
      brown adipogenesis in areas of white fat partially correlates with the body
      weight reduction detected in response to treatment with AICAR. Taken together,
      our study reveals that differentiation of brown adipocytes employs different
      signaling pathways from white adipocytes, with AMPK-mTOR cross talk a central
      mediator of this process. Promotion of BAT development in WAT by pharmacological
      activation of AMPK may have potential in treating obesity by acting on energy
      dissipation.

PMID- 20133459
TI  - Work-related Helicobacter pylori infection among sewage workers in municipal
      wastewater treatment plants in Belgium.
AB  - INTRODUCTION: Most studies among sewage workers of wastewater treatment plants
      (WWTPs) have found a higher prevalence of gastrointestinal symptoms than among
      non-sewage exposed workers. Waterborne transmission of Helicobacter pylori (H
      pylori) has been hypothesised, as the bacteria can survive into an aqueous
      environment and has been detected in sewage. A health and hygiene questionnaire
      has demonstrated a higher prevalence of peptic ulcers among Belgian WWTP
      operators and maintenance workers than among non-sewage exposed colleagues.
      OBJECTIVES: To assess the seroprevalence of H pylori infection in Belgian sewage
      workers at municipal WWTPs, and to determine whether sewage exposure is an
      important risk factor for acquisition of H pylori and the possible association
      with gastrointestinal symptoms. METHODS: A seroprevalence study of H pylori
      antibodies was conducted among 317 WWTP employees (operators, maintenance
      workers, laboratory personnel, other job). Information about demographic
      variables, possible H pylori risk factors, working history, and history of
      current gastrointestinal symptoms during last 3 months was obtained by a
      questionnaire. The presence of H pylori IgG was investigated with an ELISA. The
      results were compared with those of 250 employees of a pharmaceutical company
      (operators, maintenance workers, laboratory personnel). RESULTS: The prevalence
      of H pylori IgG antibodies among sewage workers was 16.7% (95% CI 12.6 to 20.8%)
      compared to 13.6% (95% CI 9.4 to 17.8%) among the control group. In a logistic
      regression model with controlling for age and educational levels, OR
      study/control group was 1.02 (95% CI 0.58 to 1.80 with p=0.93). No significant
      associations were found between the H pylori status and gastrointestinal
      symptoms, occupational exposures in different tasks, nor with hygienic practices.
      CONCLUSIONS: Our results do not suggest that H pylori infection is a probable
      cause of part of gastrointestinal symptoms among Flemish municipal sewage workers
      of WWTPs.

PMID- 20133460
TI  - Betel quid seller syndrome.

PMID- 20133461
TI  - Tetraiodothyroacetic acid (tetrac) and nanoparticulate tetrac arrest growth of
      medullary carcinoma of the thyroid.
AB  - CONTEXT: Tetraiodothyroacetic acid (tetrac) blocks angiogenic and tumor cell
      proliferation actions of thyroid hormone initiated at the cell surface hormone
      receptor on integrin alphavbeta3. Tetrac also inhibits angiogenesis initiated by
      vascular endothelial growth factor and basic fibroblast growth factor. OBJECTIVE:
      We tested antiangiogenic and antiproliferative efficacy of tetrac and tetrac
      nanoparticles (tetrac NP) against human medullary thyroid carcinoma (h-MTC)
      implants in the chick chorioallantoic membrane (CAM) and h-MTC xenografts in the
      nude mouse. DESIGN: h-MTC cells were implanted in the CAM model (n = 8 per
      group); effects of tetrac and tetrac NP at 1 microg/CAM were determined on tumor
      angiogenesis and tumor growth after 8 d. h-MTC cells were also implanted sc in
      nude mice (n = 6 animals per group), and actions on established tumor growth of
      unmodified tetrac and tetrac NP ip were determined. RESULTS: In the CAM, tetrac
      and tetrac NP inhibited tumor growth and tumor-associated angiogenesis. In the
      nude mouse xenograft model, established 450-500 mm(3) h-MTC tumors were reduced
      in size over 21 d by both tetrac formulations to less than the initial cell mass
      (100 mm(3)). Tumor tissue hemoglobin content of xenografts decreased by 66% over
      the course of administration of each drug. RNA microarray and quantitative real
      time PCR of tumor cell mRNAs revealed that both tetrac formulations significantly
      induced antiangiogenic thrombospondin 1 and apoptosis activator gene expression.
      CONCLUSIONS: Acting via a cell surface receptor, tetrac and tetrac NP inhibit
      growth of h-MTC cells and associated angiogenesis in CAM and mouse xenograft
      models.

PMID- 20133462
TI  - Reversible hyperinsulinemic hypoglycemia after gastric bypass: a consequence of
      altered nutrient delivery.
AB  - CONTEXT: Severe hypoglycemia after Roux-en-Y gastric bypass surgery (RYGB) is an
      increasingly recognized condition, characterized by neuroglycopenia and
      inappropriately elevated insulin concentrations that occur primarily in the
      postprandial state. Both pathophysiology and treatment of this disorder remain
      elusive, but it has been postulated that hyperplasia and/or hypertrophy of beta
      cells due to morbid obesity and/or postsurgical nesidioblastosis may contribute.
      OBJECTIVE: The objective of this study was to elucidate the pathophysiology of
      this condition; specifically, we hypothesized that metabolic abnormalities were a
      function of altered nutrient transit through the gastrointestinal tract rather
      than anatomical changes to pancreatic beta-cells that would lead to consistently
      high insulin secretion irrespective of nutrient transit route.
      DESIGN/SETTING/SUBJECT/OUTCOME MEASURES: We describe a unique case wherein
      gastrostomy tube (GT) insertion into the remnant stomach reversed neuroglycopenic
      symptoms. This subject was admitted to a university hospital research center for
      standardized measurement of glucose, insulin, and incretin hormones including
      glucagon-like peptide-1, gastric-inhibitory peptide, and glucagon. RESULTS:
      Standardized liquid meal administration via GT vs. oral route demonstrated
      complete reversal of severe metabolic abnormalities that included hypersecretion
      of insulin and GLP-1. CONCLUSION: Post-RYGB hyperinsulinemia and hypoglycemia
      result entirely from altered nutrient delivery rather than generalized
      hyperfunction of beta-cells due to presurgical hypertrophy/hyperfunction or
      postsurgical nesidioblastosis. These findings support the use of GT for treatment
      of severe cases and have implications for surgical manipulations that may
      reverse/prevent this condition.

PMID- 20133463
TI  - Sex hormone-binding globulin as an independent determinant of cortical bone
      status in men at the age of peak bone mass.
AB  - CONTEXT: Sex steroids are important determinants of the skeletal development,
      growth, and maintenance after achievement of peak bone mass. A large fraction of
      these hormones are bound by SHBG, and previous studies have shown that SHBG could
      be a determinant of bone characteristics. OBJECTIVE: We investigated associations
      of serum SHBG levels with cortical and trabecular bone characteristics in young
      healthy men. DESIGN AND SETTINGS: A total of 677 healthy male siblings aged 25-45
      yr were recruited in a cross-sectional, population-based study. MAIN OUTCOMES:
      Areal bone parameters were assessed using dual-energy x-ray absorptiometry.
      Cortical bone parameters at the tibia and radius and trabecular vBMD at the
      radius were assessed using peripheral quantitative computed tomography. Serum
      testosterone, estradiol, and SHBG levels were measured using immunoassays.
      RESULTS: Regression models including age, height, and weight showed that SHBG
      levels were positively associated with bone area at the hip and the whole body,
      but not with areal bone mineral density (BMD). Higher SHBG levels were associated
      with a larger cortical bone area and periosteal and endosteal circumferences at
      both the tibia and the radius, whereas trabecular volumetric BMD at the radius
      was negatively associated with SHBG levels. Associations persisted after
      adjustment for (free) sex steroid levels. No associations were found with
      cortical volumetric BMD or cortical thickness. CONCLUSION: In this population of
      healthy adult men at the age of peak bone mass, SHBG levels were positively
      associated with cortical bone size, independently from sex-steroid levels. This
      suggests a possible independent role of SHBG in the determination of adult bone
      size.

PMID- 20133464
TI  - Identification of a second kindred with familial hypocalciuric hypercalcemia type
      3 (FHH3) narrows localization to a <3.5 megabase pair region on chromosome
      19q13.3.
AB  - CONTEXT: Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogenous
      disorder that consists of three defined types, FHH1, FHH2, and FHH3 whose
      chromosomal locations are 3q21.1, 19p, and 19q13, respectively. FHH1, caused by
      mutations of the calcium-sensing receptor (CASR), occurs in more than 65% of
      patients, whereas the abnormalities underlying FHH2 and FHH3, which have each
      been described in single North American kindreds, are unknown. OBJECTIVE: The aim
      of this study was to determine the basis of FHH in a proband, who did not have
      CASR mutations, and her kindred. PATIENTS AND METHODS: The proband was a 43-yr
      old woman who presented with a corrected serum calcium of 2.74 mmol/liter (normal
      = 2.15-2.55 mmol/liter), a serum PTH of 47 pg/ml (normal = 10-65 pg/ml), and a
      urinary calcium clearance:creatinine clearance of 0.006. She did not have a CASR
      mutation within the coding region and splice sites, and 24 members from three
      generations of her kindred were ascertained and investigated for serum
      abnormalities and cosegregation with polymorphic loci from chromosomes 3q21.1 and
      19q13 using leukocyte DNA. RESULTS: Sixteen members were hypercalcemic with
      normal or elevated serum PTH concentrations and mild hypophosphatemia, features
      consistent with FHH3. Use of microsatellite and single nucleotide polymorphic
      loci from chromosome 19q13.3 demonstrated cosegregation with FHH in the kindred,
      with a peak LOD score = 5.98 at 0% recombination with D19S412. Analysis of
      recombinants mapped FHH to a 3.46-Mbp interval flanked centromerically by single
      nucleotide polymorphism rs1990932 and telomerically by D19S604. CONCLUSIONS: FHH3
      may explain the calcium homeostasis disorder in those FHH patients who do not
      have CASR mutations.

PMID- 20133465
TI  - Estrogen negative feedback on gonadotropin secretion: evidence for a direct
      pituitary effect in women.
AB  - CONTEXT: Studies in humans and animals indicate that estrogen negative feedback
      occurs at the level of the hypothalamus, but it is unclear whether estrogen also
      exerts an inhibitory effect directly at the pituitary. OBJECTIVES: The aim of the
      study was to determine whether estrogen has a direct negative feedback effect at
      the pituitary and whether this varies with aging. DESIGN AND SETTING: A GnRH
      antagonist and graded doses of GnRH were used to isolate pituitary responsiveness
      before and after estrogen administration in Clinical Research Center studies at
      an academic medical center. SUBJECTS: Subjects were healthy postmenopausal women
      aged 48-56 yr (n = 8) or 70-75 yr (n= 8). INTERVENTIONS: A suppressive dose of
      the NAL-GLU GnRH antagonist was administered, followed by graded doses of GnRH
      before and after 1 month of estrogen administration. RESULTS: LH and FSH
      responses to GnRH decreased after estrogen administration (P = 0.01 and P =
      0.0001, respectively). The ratio of FSH to LH amplitudes decreased in response to
      estrogen (P = 0.04) indicating a greater sensitivity of FSH than LH to inhibition
      by estrogen. The inhibitory effect of estrogen on FSH was attenuated with aging
      (P = 0.02), but was maintained for LH (P = 0.4). CONCLUSIONS: Studies that
      control for endogenous GnRH and estradiol demonstrate a direct pituitary site of
      estrogen negative feedback on LH and FSH responsiveness to GnRH in women. The
      effect of estrogen on FSH responsiveness is greater than on LH and is attenuated
      with aging. These studies indicate that estrogen negative feedback occurs
      directly at the pituitary and contributes to the differential regulation of FSH
      and LH secretion.

PMID- 20133466
TI  - Update in vitamin D.
AB  - The past decade, particularly the last 18 months, witnessed a vigorous increase
      in interest in vitamin D from both the lay and biomedical worlds. Much of the
      growing interest in vitamin D is powered by new data being extracted from the
      National Health and Nutrition Examination Survey (NHANES). The newest statistics
      demonstrate that more than 90% of the pigmented populace of the United States
      (Blacks, Hispanics, and Asians) now suffer from vitamin D insufficiency (25
      hydroxyvitamin D <30 ng/ml), with nearly three fourths of the white population in
      this country also being vitamin D insufficient. This represents a near doubling
      of the prevalence of vitamin D insufficiency seen just 10 yr ago in the same
      population. This review attempts to provide some explanation for: 1) the rapid
      decline in vitamin D status in the United States; 2) the adverse impact of
      vitamin D insufficiency on skeletal, infectious/inflammatory, and metabolic
      health in humans; and 3) the therapeutic rationale and reliable means for
      vigorous supplementation of our diets with vitamin D.

PMID- 20133467
TI  - Hypophosphatemic osteomalacia after low-dose adefovir dipivoxil therapy for
      hepatitis B.

PMID- 20133468
TI  - The use of functional imaging in a patient with head and neck paragangliomas.

PMID- 20133469
TI  - Luminal influences to orchestrate gastroenterological hormone secretion: the fat,
      long-chain Fatty Acid, cholecystokinin, glucagon-like Peptide 1 axis.

PMID- 20133470
TI  - Off-label use of recombinant igf-I to promote growth: is it appropriate?

PMID- 20133471
TI  - The brave new world of function-promoting anabolic therapies: testosterone and
      frailty.

PMID- 20133472
TI  - Molecular signatures in T-cell lymphoma.

PMID- 20133473
TI  - EBV meets its match.

PMID- 20133474
TI  - The tale of two COXs.

PMID- 20133475
TI  - Getting personal with B19 parvovirus.

PMID- 20133476
TI  - Impact of the host genetic background on prognosis of chronic lymphocytic
      leukemia.

PMID- 20133477
TI  - Patient characteristics and quality dimensions related to patient satisfaction.
AB  - OBJECTIVE: To examine the relation of respondents' characteristics, and perceived
      quality dimensions of health care to overall patient satisfaction in out-patient
      hospital care. DESIGN: A questionnaire concerning the perceived quality of health
      care sent to patients in out-patient medical care. SETTING: All medical centres
      in Ostergotland County, Sweden, during a period in 2007. PARTICIPANTS: Seven
      thousand two hundred and forty-five patients aged 20 or older responded to the
      survey and provided their own ratings of the care. Main outcome measure Global
      patient satisfaction as the overall rating of the encounter at the medical
      centre. The relation between respondent characteristics, quality dimensions and
      global satisfaction was examined using linear regression. RESULTS: Younger
      patients in emergency care were the least satisfied group (54%) and older
      patients with excellent health status were the most satisfied group (90%).
      Patients with perceived better health status and those with less education were
      more satisfied than those with more education or poorer health status. The two
      dimensions most strongly positively associated with global satisfaction were
      receiving the expected medical help and being treated well by the doctor. To wait
      at the reception without getting information correlated negatively to patient
      satisfaction, and participation in the medical decision-making correlated
      positively. CONCLUSIONS: By using a complete patient population, including all
      types of medical specialities, we have identified a set of common respondent
      characteristics and quality dimensions that are related to global satisfaction in
      out-patient hospital care.

PMID- 20133478
TI  - HSP72 inhibits Smad3 activation and nuclear translocation in renal epithelial-to
      mesenchymal transition.
AB  - Although heat shock protein 72 (HSP72) ameliorates renal tubulointerstitial
      fibrosis by inhibiting epithelial-to-mesenchymal transition (EMT), the underlying
      mechanism is unknown. Because Smad proteins transduce TGF-beta signaling from the
      cytosol to the nucleus and HSP72 assists in protein folding and facilitates
      nuclear translocation, we investigated whether HSP72 inhibits TGF-beta-induced
      EMT by modulating Smad expression, activation, and nuclear translocation. To
      evaluate the roles of distinct HSP72 structural domains in these processes, we
      constructed vectors that expressed wild-type HSP72 or mutants lacking either the
      peptide-binding domain (HSP72-DeltaPBD), which is responsible for substrate
      binding and refolding, or the nuclear localization signal (HSP72-DeltaNLS).
      Overexpression of wild-type HSP72 or HSP72-DeltaNLS inhibited TGF-beta1-induced
      EMT, but HSP72-DeltaPBD did not, suggesting a critical role for the PBD in this
      inhibition. HSP72 overexpression inhibited TGF-beta1-induced phosphorylation and
      nuclear translocation of Smad3 and p-Smad3, but not Smad2; these inhibitory
      effects required the PBD but not the NLS. Coimmunoprecipitation assays suggested
      a physical interaction between Smad3 and the PBD. siRNA knockdown of endogenous
      HSP72 enhanced both TGF-beta1-induced Smad3 phosphorylation and EMT and confirmed
      the interaction of HSP72 with both Smad3 and p-Smad3. In vivo, induction of HSP72
      by geranylgeranylacetone suppressed Smad3 phosphorylation in renal tubular cells
      after unilateral ureteral obstruction. In conclusion, HSP72 inhibits EMT in renal
      epithelial cells primarily by exerting domain-specific effects on Smad3
      activation and nuclear translocation.

PMID- 20133479
TI  - Targeted inactivation of EGF receptor inhibits renal collecting duct development
      and function.
AB  - The ureteric bud (UB) expresses high levels of the EGF receptor (EGFR) during
      kidney development, but its function in this setting is unclear. Here, Egfr mRNA
      was abundant in medullary portions of the UB trunk but absent from the branching
      UB tips during embryogenesis. Homozygous Egfr knockout did not affect the pattern
      of UB arborization, but renal papillae were hypoplastic and exhibited widespread
      apoptosis of tubular cells. Because these EGFR-deficient mice die within 1 week
      of life, we targeted Egfr inactivation to the renal collecting ducts using Cre
      lox technology with a Hoxb7-Cre transgene. This targeted inactivation of Egfr led
      to a thin renal medulla, and at 7 weeks of age, the mice had moderate polyuria
      and reduced urine-concentrating ability. At 30 to 33 weeks, water deprivation
      demonstrated a continued urine-concentrating defect despite similar levels of
      vasopressin between knockout mice and littermate controls. Taken together, these
      results suggest that unlike other tyrosine kinases expressed at the UB tip, EGFR
      functions primarily to drive elongation of the emerging collecting ducts and to
      optimize urine-concentrating ability.

PMID- 20133480
TI  - ZONAB promotes proliferation and represses differentiation of proximal tubule
      epithelial cells.
AB  - Epithelial polarization modulates gene expression. The transcription factor
      zonula occludens 1 (ZO-1)-associated nucleic acid binding protein (ZONAB) can
      shuttle between tight junctions and nuclei, promoting cell proliferation and
      expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), but
      whether it also represses epithelial differentiation is unknown. Here, during
      mouse kidney ontogeny and polarization of proximal tubular cells (OK cells),
      ZONAB and PCNA levels decreased in parallel and inversely correlated with
      increasing apical differentiation, reflected by expression of megalin/cubilin,
      maturation of the brush border, and extension of the primary cilium. Conversely,
      ZONAB reexpression and loss of apical differentiation markers provided a
      signature for renal clear cell carcinoma. In confluent OK cells, ZONAB
      overexpression increased proliferation and PCNA while repressing megalin/cubilin
      expression and impairing differentiation of the brush border and primary cilium.
      Reporter and chromatin immunoprecipitation assays demonstrated that megalin and
      cubilin are ZONAB target genes. Sparsely plated OK cells formed small islands
      composed of distinct populations: Cells on the periphery, which lacked external
      tight junctions, strongly expressed nuclear ZONAB, proliferated, and failed to
      differentiate; central cells, surrounded by continuous junctions, lost nuclear
      ZONAB, stopped proliferating, and engaged in apical differentiation. Taken
      together, these data suggest that ZONAB is an important component of the
      mechanisms that sense epithelial density and participates in the complex
      transcriptional networks that regulate the switch between proliferation and
      differentiation.

PMID- 20133481
TI  - Of mice and men: therapeutic mTOR inhibition in polycystic kidney disease.

PMID- 20133482
TI  - Diagnostic application of the A(1c) assay in renal disease.

PMID- 20133483
TI  - Propensity-matched mortality comparison of incident hemodialysis and peritoneal
      dialysis patients.
AB  - Contemporary comparisons of mortality in matched hemodialysis and peritoneal
      dialysis patients are lacking. We aimed to compare survival of incident
      hemodialysis and peritoneal dialysis patients by intention-to-treat analysis in a
      matched-pair cohort and in subsets defined by age, cardiovascular disease, and
      diabetes. We matched 6337 patient pairs from a retrospective cohort of 98,875
      adults who initiated dialysis in 2003 in the United States. In the primary
      intention-to-treat analysis of survival from day 0, cumulative survival was
      higher for peritoneal dialysis patients than for hemodialysis patients (hazard
      ratio 0.92; 95% CI 0.86 to 1.00, P = 0.04). Cumulative survival probabilities for
      peritoneal dialysis versus hemodialysis were 85.8% versus 80.7% (P < 0.01), 71.1%
      versus 68.0% (P < 0.01), 58.1% versus 56.7% (P = 0.25), and 48.4% versus 47.3% (P
      = 0.50) at 12, 24, 36, and 48 months, respectively. Peritoneal dialysis was
      associated with improved survival compared with hemodialysis among subgroups with
      age <65 years, no cardiovascular disease, and no diabetes. In a sensitivity
      analysis of survival from 90 days after initiation, we did not detect a
      difference in survival between modalities overall (hazard ratio 1.05; 95% CI 0.96
      to 1.16), but hemodialysis was associated with improved survival among subgroups
      with cardiovascular disease and diabetes. In conclusion, despite hazard ratio
      heterogeneity across patient subgroups and nonconstant hazard ratios during the
      follow-up period, the overall intention-to-treat mortality risk after dialysis
      initiation was 8% lower for peritoneal dialysis than for matched hemodialysis
      patients. These data suggest that increased use of peritoneal dialysis may
      benefit incident ESRD patients.

PMID- 20133484
TI  - Integrating human and rodent data to identify the genetic factors involved in
      chronic kidney disease.
AB  - The increasing numbers of patients with chronic kidney disease combined with no
      satisfying interventions for preventing or curing the disease emphasize the need
      to better understand the genes involved in the initiation and progression of
      complex renal diseases, their interactions with other host genes, and the
      environment. Linkage and association studies in human, rat, and mouse have been
      successful in identifying genetic loci for various disease-related phenotypes but
      have thus far not been very successful identifying underlying genes. The purpose
      of this review is to summarize the progress in human, rat, and mouse genetic
      studies to show the concordance between the loci among the different species. The
      collective utilization of human and nonhuman mammalian datasets and resources can
      lead to a more rapid narrowing of disease loci and the subsequent identification
      of candidate genes. In addition, genes identified through these methods can be
      further characterized and investigated for interactions using animal models,
      which is not possible in humans.

PMID- 20133485
TI  - Time to recognize an overlooked trait.

PMID- 20133486
TI  - ZO-1 and ZONAB interact to regulate proximal tubular cell differentiation.

PMID- 20133487
TI  - Endothelin receptor antagonists in proteinuric renal disease: every rose has its
      thorn.

PMID- 20133488
TI  - Cardiovascular effects of angiotensin converting enzyme inhibition or angiotensin
      receptor blockade in hemodialysis: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular (CV) disease causes significant
      morbidity and mortality among the hemodialysis (HD) population. This meta
      analysis was performed to determine whether angiotensin converting enzyme
      inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) reduce fatal and
      nonfatal CV events and left ventricular (LV) mass in patients receiving HD.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Studies were identified by
      searching electronic databases, bibliographies, and conference proceedings. Two
      reviewers independently selected randomized controlled trials using ACEIs or ARBs
      compared with control among patients receiving HD. Studies were independently
      assessed for inclusion, quality, and data extraction. Random-effects models were
      used to estimate the pooled relative risk (RR) for CV outcomes and the weighted
      mean difference (WMD) for pooled change-from-baseline comparisons for LV mass for
      ACEI or ARB treated patients compared with control. RESULTS: Compared with
      control, the RR of CV events associated with ACEI or ARB use was 0.66 [95%
      confidence interval (CI) 0.35 to 1.25; P = 0.20]. ACEI or ARB use resulted in a
      statistically significant reduction in LV mass, with a WMD of 15.4 g/m(2) (95% CI
      7.4 to 23.3; P < 0.001). CONCLUSIONS: Treatment with an ACEI or ARB reduced LV
      mass in patients receiving HD. However, their use was not associated with a
      statistically significant reduction in the risk of fatal and nonfatal CV events.
      Larger, high-quality trials in the HD population are required to determine if the
      effects of ACEI or ARB therapy on LV mass translate into decreased CV morbidity
      and mortality.

PMID- 20133489
TI  - The circulating inactive form of matrix gla protein is a surrogate marker for
      vascular calcification in chronic kidney disease: a preliminary report.
AB  - BACKGROUND AND OBJECTIVES: Vitamin K-dependent matrix Gla protein (MGP) acts as a
      calcification inhibitor in vitro and in vivo. The present study was performed to
      (1) determine plasma levels of the inactive, dephosphorylated, uncarboxylated MGP
      (dp-ucMGP) in a cohort of patients at different stages of chronic kidney disease
      (CKD) and (2) evaluate the association between dp-ucMGP levels on one hand and
      aortic calcification and mortality on the other. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: 107 patients (67 +/- 13 years; 60% male; 32% at CKD stages 2 to 3,
      31% at stages 4 to 5, 37% at stage 5D) were assayed for dp-ucMGP and underwent
      multislice spiral computed tomography scans to quantify aortic calcification at
      baseline. They were prospectively monitored for mortality. RESULTS: Plasma dp
      ucMGP levels augmented progressively with CKD stage, with a significant
      difference from CKD stage 4. CKD stage, hemoglobin, age, and coumarin use were
      independently associated with plasma dp-ucMGP levels. Furthermore, plasma dp
      ucMGP and age were positively and independently associated with the aortic
      calcification score. During follow-up (802 +/- 311 days), 34 patients died (20
      from cardiovascular events). In a crude analysis, [plasma dp-ucMGP] > 921 pM was
      associated with overall mortality; this association was lost after adjusting for
      both age and the calculated propensity score. CONCLUSIONS: Plasma dp-ucMGP
      increased progressively in a CKD setting and was associated with the severity of
      aortic calcification. Plasma dp-ucMGP could thus be a surrogate marker for
      vascular calcification in CKD.

PMID- 20133490
TI  - Undiagnosed diabetes in kidney transplant candidates: a case-finding strategy.
AB  - BACKGROUND AND OBJECTIVES: Guidelines recommend that candidates for kidney
      transplantation (KTx) who do not have diabetes perform a pretransplantation oral
      glucose tolerance test (OGTT) when fasting plasma glucose (FPG) is <110 mg/dl
      (<6.1 mmol/L); however, the OGTT is potentially costly and cumbersome. We studied
      the role of the OGTT for diagnosing diabetes and the accuracy of FPG and glycated
      hemoglobin (HbA(1c)) for predicting a diabetic OGTT before KTx. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: In this cross-sectional study, 889 first single
      kidney transplant candidates without diabetes, mainly white, performed an OGTT
      during the transplantation workup. Results were studied using receiver operating
      characteristic analysis. RESULTS: Of 72 (8.1%) patients with undiagnosed
      diabetes, only 16 (22%) had a diabetic FPG (> or =126 mg/dl [> or =7.0 mmol/L]).
      In patients with a nondiabetic FPG, diabetes (2-hour plasma glucose [2h-PG] > or
      =200 mg/dl [> or =11.1 mmol/L]) was predicted by FPG but not by HbA(1c).
      Performing the OGTT in patients with FPG 92 to 125 mg/dl (5.1 to 6.9 mmol/L)
      identified 65 (90%) patients with diabetes (16 by FPG, 49 by 2h-PG) and required
      seven OGTTs per patient identified. Subjecting all patients with FPG <110 mg/dl
      (<6.1 mmol/L) to the OGTT identified 60 (83%) patients with diabetes (16 by FPG,
      44 by 2h-PG) but required 14 OGTTs per patient. CONCLUSIONS: The OGTT was
      paramount in finding most cases of undiagnosed diabetes before KTx. FPG but not
      HbA(1c) predicted a diabetic OGTT. We suggest that white KTx candidates without
      diabetes perform a pretransplantation OGTT when FPG is 92 to 125 mg/dl (5.1 to
      6.9 mmol/L).

PMID- 20133491
TI  - A phase III, randomized, double-blind, placebo-controlled study of tenecteplase
      for improvement of hemodialysis catheter function: TROPICS 3.
AB  - BACKGROUND AND OBJECTIVES: Despite widespread use of tunneled hemodialysis (HD)
      catheters, their utility is limited by the development of thrombotic
      complications. To address this problem, this study investigated whether the
      thrombolytic agent tenecteplase can restore blood flow rates (BFRs) in
      dysfunctional HD catheters. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In
      this randomized, double-blind study, patients with dysfunctional tunneled HD
      catheters, defined as a BFR <300 ml/min at -250 mmHg pressure in the arterial
      line, received 1-hour intracatheter dwell with tenecteplase (2 mg) or placebo.
      The primary endpoint was the percentage of patients with BFR > or =300 ml/min and
      an increase of > or =25 ml/min above baseline 30 minutes before and at the end of
      HD. Safety endpoints included the incidence of hemorrhagic, thrombotic, and
      infectious complications. RESULTS: Eligible patients (n = 149) were treated with
      tenecteplase (n = 74) or placebo (n = 75). Mean baseline BFR was similar for the
      tenecteplase and placebo groups at 151 and 137 ml/min, respectively. After a 1
      hour dwell, 22% of patients in the tenecteplase group had functional catheters
      compared with 5% among placebo controls (P = 0.004). At the end of dialysis, mean
      change in BFR was 47 ml/min in the tenecteplase group versus 12 ml/min in the
      placebo group (P = 0.008). Four catheter-related bloodstream infections (one
      tenecteplase, three placebo) and one thrombosis (tenecteplase) were observed.
      There were no reports of intracranial hemorrhage, major bleeding, embolic events,
      or catheter-related complications. CONCLUSIONS: Tenecteplase improved HD catheter
      function and had a favorable safety profile compared with placebo.

PMID- 20133492
TI  - Control of secondary hyperparathyroidism by vitamin D receptor agonists in
      chronic kidney disease.
AB  - Effective treatment options for managing secondary hyperparathyroidism (SHPT) in
      patients with chronic kidney disease (CKD) have advanced steadily since the early
      1980s, from surgical removal of the parathyroid gland to pharmacologic
      intervention focused on reestablishing hormonal and mineral balances. In
      addition, earlier recognition of CKD via estimated GFR and educational efforts
      have led to advancements in diagnosis and treatment of elevated parathyroid
      hormone (PTH) and vitamin D deficiency. Clinical studies support the efficacy and
      safety of vitamin D receptor (VDR) agonists as effective treatments for SHPT. A
      number of considerations to ensure optimal SHPT control in CKD patients are
      apparent. VDR agonists effectively treat SHPT and vitamin D deficiency, but
      dosing needs to be optimized for each patient because the patient responds in an
      individualized manner to treatment to suppress and stabilize PTH levels. VDR
      agonist therapy should be continuous to ensure continued PTH suppression, coupled
      with strict monitoring of calcium and phosphorus to ensure compliance within
      target ranges. Awareness of the complex and beneficial effects of VDR agonists
      contributes to improved benefits in bone mineral disease and lower mortality
      risks.

PMID- 20133493
TI  - Lipopolysaccharide-binding protein-mediated Toll-like receptor 4 dimerization
      enables rapid signal transduction against lipopolysaccharide stimulation on
      membrane-associated CD14-expressing cells.
AB  - Toll-like receptor (TLR) 4/MD-2 dimerization is thought to be required for the
      initiation of signaling during innate immune responses. In this study, we
      examined the molecular mechanisms underlying receptor dimerization in the context
      of accessory molecules, i.e. CD14 and lipopolysaccharide-binding protein (LBP),
      to determine whether dimerization is required for the initiation of signaling in
      response to LPS stimulation. We found that LPS-induced TLR4/MD-2 dimerization
      occurred only in membrane-associated CD14 (mCD14)-expressing cells. Furthermore,
      dimerization required LBP, but not soluble CD14 (sCD14), as an essential serum
      component. LPS-induced signaling as assessed by IkappaB-alpha degradation,
      however, occurred in mCD14-negative cells in the presence of serum and sCD14.
      Signaling also occurred in mCD14-positive cells in the absence of serum. Time
      course studies on mCD14-positive cells have demonstrated that LPS stimulation
      induces rapid activation of nuclear factor-kappaB and p38 in the presence of LBP
      (TLR4/MD-2 receptor dimerization) as compared with stimulation without LBP
      (receptor non-dimerization). This early activation was blocked by inhibitory anti
      CD14 mAb. These studies suggest that LPS-induced TLR4/MD-2 receptor dimerization
      is not essential for signaling but prompts rapid signaling during innate immune
      responses.

PMID- 20133494
TI  - Targeting apoptosis in the heart of streptozotocin-induced diabetic rats.
AB  - OBJECTIVES: The aim of the current study was to address the issue of
      cardiomyocyte apoptosis as a possible contributor in the development of diabetic
      cardiomyopathy and whether it would be possible to suppress this apoptosis by the
      use of a peroxisome proliferator-activated receptor (PPAR)-alpha agonist
      (fenofibrate) or a PPAR-gamma agonist (rosiglitazone). METHODS: Ten normal male
      albino rats (group I) were injected intraperitoneally (IP) by a single dose of
      saline and served as a control for group II. Thirty male albino rats were made
      diabetic by IP streptozotocin (STZ) injection and were divided into 3 groups:
      group II (nontreated diabetic rats), groups III and IV (diabetic rats treated
      with PPAR-gamma agonist (rosiglitazone), and PPAR-alpha agonist (fenofibrate)
      respectively, for 12 weeks starting 1 week following STZ injection. RESULTS: The
      studied drugs decreased left ventricular to body weight ratio and cardiac:
      caspase-3, tumor necrosis factor-alpha, hydroxyproline, free fatty acids (FFAs)
      as well as triglycerides (TGs) and improved oxidative stress parameters as well
      as left ventricular papillary muscle developed tension (DT). CONCLUSIONS: The
      results of the current study support the hypothesis that apoptosis plays a key
      role in the pathophysiology of diabetic cardiomyopathy and demonstrate that the
      use of PPAR-alpha and -gamma agonists might have a protective role against
      diabetic cardiomyopathy.

PMID- 20133495
TI  - Effects of labetalol on hemodynamic parameters and soluble biomarkers of
      inflammation in acute coronary syndrome in patients with active cocaine use.
AB  - Cocaine use is associated with increased cardiovascular mortality and can promote
      acute coronary syndrome (ACS). Use of beta-blockers is controversial in patients
      who use cocaine, and the safety and efficacy of these medications in ACS in
      patients actively using cocaine is unknown. We enrolled 90 patients with ACS and
      positive urine drug screen for cocaine. Patients received standard ACS therapy
      plus either labetalol (n = 60) or diltiazem (n = 30). Blood pressure and heart
      rate were measured at baseline and 48 hours. Levels of serum CD40 ligand,
      interleukin (IL)-6, and choline at baseline and 48 hours were determined. There
      were no baseline differences in hemodynamics or serum levels of inflammatory
      markers between the labetalol and diltiazem groups. Both groups experienced a
      significant and equivalent decrease in BP and HR at 48 hours compared with
      baseline. At 48 hours of treatment, there were significant decreases of 17% in
      CD40 ligand (P < .005) and 16% in IL-6 (P < .005) but no change in choline in the
      diltiazem group. Furthermore, in the labetalol group, there were significant
      differences of 30% in CD40 ligand (P < .005 time and group comparison), 22% in IL
      6 (P < .005 time and group comparison), and 18% in choline (P < .005 time and
      group comparison). There were no adverse events during hospitalization in any
      patients who received labetalol. In conclusion, labetalol appears to be safe in
      cocaine-associated ACS. Furthermore, labetalol provides a beneficial hemodynamic
      response and, in comparison to diltiazem, potentiates an anti-inflammatory
      vascular response in this setting.

PMID- 20133496
TI  - L-cysteine stimulates hydrogen sulfide synthesis in myocardium associated with
      attenuation of ischemia-reperfusion injury.
AB  - Hydrogen sulfide (H( 2)S) is a biological mediator produced by enzyme-regulated
      pathways from L-cysteine, which is a substrate for cystathionine-gamma-lyase
      (CSE). In myocardium, endogenously and exogenously administered H(2)S has been
      shown to protect against ischemia-reperfusion injury. We hypothesized that L
      cysteine exerts its protective action through stimulation of H(2)S production.
      Rat isolated hearts were Langendorff-perfused and underwent 35-minute regional
      ischemia and 120-minute reperfusion. L-cysteine perfusion from 10 minutes before
      ischemia until 10 minutes after reperfusion limited infarct size in a
      concentration-dependent manner, maximal at 1 mmol/L (control 36.4% +/- 2.4% vs L
      cysteine 24.3% +/- 3.4%, P < .05). This protective action was attenuated by the
      CSE inhibitor, DL-propargylglycine (PAG) 1 mmol/L (31.4 +/- 5.9%, not significant
      vs control) but administration of the CSE cofactor pyridoxal-5'-phosphate (PLP)
      50 mumol/L did not enhance the effect of L-cysteine. Ten minutes normoxic
      perfusion with L-cysteine 1 mmol/L caused a 3-fold increase in myocardial H(2)S
      concentration (0.64 +/- 0.16 vs 2.01 +/- 0.07 mumol/g protein, P < .01), an
      effect that was significantly attenuated by PAG (1.17 +/- 0.15 mumol/g protein).
      These data provide evidence that exogenous L-cysteine administration limits
      ischemia-reperfusion injury through a mechanism that appears to be at least
      partially dependent on H(2)S synthesis.

PMID- 20133497
TI  - Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow,
      infarct size, and blood flow following ischemia/ reperfusion in the rabbit.
AB  - GP531, a potent, second-generation adenosine-regulating agent, is
      pharmacologically silent under basal conditions but increases localized
      endogenous adenosine during ischemia. GP531 improves functional recovery after
      myocardial ischemia, but its effects on infarct size and no-reflow have not been
      reported. The objective was to determine whether GP531 reduces necrosis and the
      anatomic no-reflow defect and to evaluate its effects on regional myocardial
      blood flow (RMBF). GP531 was given as a loading dose plus infusion at 2 doses
      (700 microg/kg and 10 microg/kg per minute or 2100 microg/kg and 30 microg/kg per
      minute) or vehicle, starting 12 minutes before a 30-minute coronary occlusion and
      throughout 3 hours reperfusion in rabbits. Risk zone was delineated by blue dye,
      necrosis by tetrazolium staining, RMBF by radioactive microspheres, and no-reflow
      defect by thioflavin S. The extent of the ischemic risk zone was similar in all
      groups. Low-dose GP531 reduced infarct size by 34% (0.33 +/- 0.4 of the risk
      zone) compared with vehicle (0.50 +/- 0.4, P < .01) and reduced the extent of the
      anatomic no-reflow zone by 31% compared with vehicle (0.25 +/- 0.3 of the risk
      zone vs 0.36 +/- 0.4 in the vehicle group, P < .05). Infarct size and zone of no
      reflow in the high dose were reduced by 22% and 16%, respectively (P = NS vs the
      other 2 groups). GP531 did not affect hemodynamics or blood flow. Thus, GP531 was
      effective at the lower dose evaluated in this study, reducing the severity of
      ischemic/reperfusion injury, without inducing the adverse hemodynamic effects
      associated with adenosine administration such as bradycardia and hypotension.

PMID- 20133498
TI  - Youth living with HIV and problem substance use: elevated distress is associated
      with nonadherence and sexual risk.
AB  - PURPOSE: To examine health risk behaviors in distressed youth living with HIV
      (YLH) with problem substance use. METHODS: Assessed distress, antiretroviral
      (ARV) adherence, and unprotected sex in a racially and geographically diverse
      sample of 122 YLH. RESULTS: A total of 87% of distressed YLH reported
      significantly more past-month ARV nonadherence (odds ratio [OR] = 7.15) and were
      more likely to have unprotected sex under the influence (OR = 5.14) than
      nondistressed youth. CONCLUSIONS: Distressed YLH with problem substance use may
      benefit from interventions to improve adherence and to decrease sexual risk,
      especially while under the influence of drugs.

PMID- 20133499
TI  - Predicting response to EGFR inhibitors in metastatic colorectal cancer: current
      practice and future directions.
AB  - The identification of KRAS mutational status as a predictive marker of response
      to antibodies against the epidermal growth factor receptor (EGFR) has been one of
      the most significant and practice-changing recent advances in colorectal cancer
      research. Recently, data suggesting a potential role for other markers (including
      BRAF mutations, loss of phosphatase and tension homologue deleted on chromosome
      ten expression, and phosphatidylinositol-3-kinase-AKT pathway mutations) in
      predicting response to anti-EGFR therapy have emerged. Ongoing clinical trials
      and correlative analyses are essential to definitively identify predictive
      markers and develop therapeutic strategies for patients who may not derive
      benefit from anti-EGFR therapy. This article reviews recent clinical trials
      supporting the predictive role of KRAS, recent changes to clinical guidelines and
      pharmaceutical labeling, investigational predictive molecular markers, and newer
      clinical trials targeting patients with mutated KRAS.

PMID- 20133500
TI  - IDH1 gene mutations: a new paradigm in glioma prognosis and therapy?

PMID- 20133501
TI  - More is better: a multimodality approach to cancer cachexia.

PMID- 20133502
TI  - Economic evaluation of the DiAMOND randomized trial: cost and outcomes of 2
      decision aids for mode of delivery among women with a previous cesarean section.
AB  - BACKGROUND: Maternal preferences should be considered in decisions about mode of
      delivery following a previous cesarean, but risks and benefits are unclear.
      Decision aids can help decision making, although few studies have assessed costs
      in conjunction with effectiveness. OBJECTIVE: Economic evaluation of 2 decision
      aids for women with 1 previous cesarean. DESIGN: Cost-consequences analysis.
      MATERIALS AND METHODS: Data sources were self-reported resource use and outcome
      and published national unit costs. The target population was women with 1
      previous cesarean. The time horizon was 37 weeks' gestation and 6 weeks
      postnatal. The perspective was health care delivery system. The interventions
      were usual care, usual care plus an information program, and usual care plus a
      decision analysis program. The outcome measures were costs to the National Health
      Service (NHS) in the United Kingdom (UK), score on the Decisional Conflict Scale,
      and mode of delivery. RESULTS OF MAIN ANALYSIS: Cost of delivery represented 84%
      of the total cost; mode of delivery was the most important determinant of cost
      differences across the groups. Mean (SD) total cost per mother and baby: 2033
      (677) for usual care, 2069 (738) for information program, and 2019 (741) for
      decision analysis program. Decision aids reduced decisional conflict. Women using
      the decision analysis program had fewest cesarean deliveries. RESULTS OF
      SENSITIVITY ANALYSIS: Applying a cost premium to emergency cesareans over
      electives had little effect on group comparisons. Conclusions were unaffected.
      LIMITATIONS: Disparity in timing of outcomes and costs, data completeness, and
      quality. CONCLUSIONS: Decision aids can reduce decisional conflict in women with
      a previous cesarean section when deciding on mode of delivery. The information
      program could be implemented at no extra cost to the NHS. The decision analysis
      program might reduce the rate of cesarean sections without any increase in costs.

PMID- 20133503
TI  - Securinine induces p73-dependent apoptosis preferentially in p53-deficient colon
      cancer cells.
AB  - The identification of agents that preferentially kill cancer cells while
      protecting normal cells offers the potential to overcome toxicities found in many
      existing chemotherapeutic agents. Because p53 is frequently inactivated in
      cancer, agents that preferentially kill p53-null cells and protect wild-type p53
      expressing cells are highly desirable chemotherapeutic agents. By using pairs of
      isogenic colon cancer cell lines that differ only in p53 expression (RKO and
      HCT116), securinine was found to exhibit these properties. Securinine (30 microM)
      induces apoptosis in 73% of p53-null HCT116 cells (LD(50) 17.5 microM) as opposed
      to 17.6% of HCT116 parental cells (LD(50) 50 microM) at 72 h after treatment. The
      mechanism of securinine-mediated death in p53-deficient cells involves the
      induction of the p53 family member, p73. Interestingly, the proapoptotic protein
      p73 is down-regulated in colon cancer cells expressing p53. This differential
      regulation of p73 in a p53-dependent fashion reveals a novel pathway for
      preferentially targeting cancer cells. In contrast to p53-deficient cells, cells
      expressing p53 are protected from cell death through the p53-mediated up
      regulation of p21. These studies reveal a novel approach to specifically target
      colon cancer cells lacking p53 as well as identify a novel clinically relevant
      pathway to selectively induce p73 in p53-null cells.

PMID- 20133504
TI  - Two decades of qualitative health research.

PMID- 20133505
TI  - Understanding the role of the promotora in a Latino diabetes education program.
AB  - We explore the role of the promotora de salud (health promoter) who provided
      diabetes self-management education to Puerto Rican diabetics in her community.
      The education program was developed as a hospital and community-based
      organization partnership. Information from both Spanish-language focus groups
      with 35 class participants and an in-depth interview with the promotora indicated
      patients appreciated having the classes taught in Spanish by a Latina promotora
      from their community. Respondents reported satisfaction with the program,
      increased ability to self-manage diabetes, and strengthened connections with
      other Latino diabetics. Terms patients used for the promotora included comadre,
      hijita, and buena profesora. Some of these words denote almost kinship-level
      connections, suggesting that patients were forming strong connections with the
      promotora. Specific promotora roles were identified but varied among patients,
      promotora, and the literature. This hospital and community-based organization
      partnership promotora model appears to be effective for providing chronic disease
      self-management education in an urban community setting.

PMID- 20133506
TI  - Families' and professional caregivers' views of using advanced technology to
      track people with dementia.
AB  - in this study we examined the ethical aspects of the use of the Global
      Positioning Systems (GPS) to track people with dementia. The findings are based
      on qualitative data gathered from focus groups of family and professional
      caregivers. The most important theme was the need to balance patients' need for
      safety with the need to preserve their autonomy and privacy. The main potential
      benefit of the use of GPS was related to the peace of mind of the caregivers
      themselves. The findings also suggest that caregivers' views change according to
      the locus of responsibility of the caregivers for the safety of people with
      dementia. The caregivers give preference to patients' safety more than autonomy
      when they are responsible for the patients. When the patients are under the
      responsibility of other caregivers, they give preference to patients' autonomy
      more than their safety. Overall, the variety and the depth of the views of
      different stakeholders toward the use of electronic tracking for people with
      dementia presented in this article provide a meaningful contribution to the
      ethical debate on this topic.

PMID- 20133507
TI  - Population pharmacokinetics of liraglutide, a once-daily human glucagon-like
      peptide-1 analog, in healthy volunteers and subjects with type 2 diabetes, and
      comparison to twice-daily exenatide.
AB  - The once-daily human glucagon-like peptide-1 (GLP-1) analog, liraglutide, was
      recently shown to provide improved glycemic control in subjects with type 2
      diabetes (T2D) compared with exenatide. The aim of this work is to estimate the
      population pharmacokinetics of liraglutide and make a comparison to the
      pharmacokinetic profile of exenatide. Pharmacokinetic data from 5 published
      studies of subcutaneous and intravenous administration of liraglutide to healthy
      volunteers (HV) and subjects with T2D were used to develop a population
      pharmacokinetic model in NONMEM. Exenatide data came from a published study in
      T2D. Liraglutide pharmacokinetics were adequately described using a 1-compartment
      model with sequential zero- and first-order absorption. The pharmacokinetic
      profile of once-daily liraglutide showed considerably smaller peak-to-trough
      fluctuations compared with twice-daily exenatide. A small difference in the
      estimates of absorption parameters was found between HV and subjects with T2D but
      was not clinically relevant. It was concluded that pharmacokinetic profiles
      estimated by modeling showed that liraglutide has pharmacokinetic properties
      consistent with once-daily dosing in humans and provides better pharmacokinetic
      coverage in comparison with twice-daily exenatide. Furthermore, no clinically
      relevant differences were found in liraglutide pharmacokinetics between HV and
      subjects with T2D.

PMID- 20133508
TI  - Lack of racial differences in the pharmacokinetics of subcutaneous golimumab in
      healthy Japanese and Caucasian male subjects.
AB  - This phase 1 study evaluated the single-dose pharmacokinetics and safety of
      subcutaneous golimumab, a human anti-tumor necrosis factor-alpha monoclonal
      antibody, in healthy Japanese and Caucasian subjects. Eligible subjects were
      males, aged 20 to 45 years, weighing 50 to 90 kg with a body mass index of 19 to
      30 kg/m(2). Japanese and Caucasian subjects were matched by body weight and dose
      group. Blood samples were collected through day 50 following a single
      subcutaneous injection of golimumab 50 or 100 mg. The pharmacokinetic parameters
      were determined using a noncompartmental method. All 51 subjects (24 Japanese, 27
      Caucasian) were included in the safety analysis; 47 completed the study and were
      included in the pharmacokinetic analysis. The pharmacokinetics of golimumab were
      comparable in both race groups. Peak concentrations were observed approximately 4
      to 6 days after administration. No significant differences in exposure or mean
      half-life (range, 11-13 days) were observed between Japanese and Caucasian
      subjects at the same dose level. Regardless of race, serum golimumab exposure
      increased with increasing dose. Mean apparent clearance ranged from 12 to 19
      mL/kg/d. Mean apparent volume of distribution (224-262 mL/kg) remained constant
      with an increase in dose. No antibodies to golimumab were detected. Single
      subcutaneous injections of golimumab 50 mg or 100 mg were generally well
      tolerated in these healthy male Japanese and Caucasian subjects.

PMID- 20133509
TI  - CYP3A5 but not CYP2D6 polymorphism contributes significantly to the variability
      in dextropropoxyphene disposition.
AB  - This study evaluated the effect of CYP2D6, CYP3A4, and CYP3A5 polymorphisms on
      dextropropoxyphene disposition in healthy subjects. A total of 14 healthy male
      Chinese subjects received a single oral dose of a combination tablet of 325 mg of
      paracetamol and 32.5 mg of dextropropoxyphene. Serial blood samples were
      collected for up to 24 hours to determine plasma concentrations of paracetamol,
      dextropropoxyphene, and nordextropropoxyphene by liquid chromatography-tandem
      mass spectroscopy. CYP2D6, CYP3A4, and CYP3A5 genotyping were performed using
      polymerase chain reaction-based methods. No CYP3A4 mutant alleles were detected
      in the study subjects. There were no significant differences (P > .05) in
      dextropropoxyphene and nordextropropoxyphene pharmacokinetics among CYP2D6
      genotypes. In contrast, plasma concentrations of dextropropoxyphene were
      significantly higher (peak plasma concentration, 54.4 +/- 25.5 vs 31.0 +/- 10.9
      ng/mL; area under the plasma concentration-time curve, 260.8 +/- 88.1 vs 142.3 +/
      42.4 ng x h/mL, both P < .05) and apparent oral clearance value was
      significantly lower (2.2 +/- 0.9 vs 3.6 +/- 1.4 L/h/kg, P < .05) in CYP3A5*3/*3
      (n = 8) than CYP3A5*1/*3 (n = 5) subjects. Nordextropropoxyphene exposure also
      tended to be higher in CYP3A5*3/*3 subjects, but the difference was not
      statistically significant between the 2 groups. One subject who was identified as
      a CYP3A5*1/*1 carrier exhibited a very high apparent oral clearance value of 12.5
      L/h/kg. No significant difference in paracetamol pharmacokinetics was observed
      among CYP2D6 or CYP3A5 genotypes. These results suggest that CYP3A5 but not
      CYP2D6 polymorphisms appear to exert a significant influence on
      dextropropoxyphene disposition.

PMID- 20133510
TI  - Efficacy and safety of ketoprofen patch in patients with rheumatoid arthritis: a
      randomized, double-blind, placebo-controlled study.
AB  - This study assessed the efficacy and safety of ketoprofen patch compared with
      placebo in patients who had rheumatoid arthritis and persistent wrist pain.
      Patients (N = 676)who had achieved systemic disease control with a disease
      modifying antirheumatic drug and/or systemic corticosteroid, but still had
      persistent wrist pain, were randomized to a 2-week course of once-daily treatment
      with application of a 20-mg ketoprofen patch or a placebo patch to the wrist. The
      primary efficacy end point was the percent change from baseline to the end of
      treatment in the intensity of wrist pain scored by each patient on a 100-mm
      visual analog scale. The mean +/- SD percent change on the pain intensity scale
      was significantly larger in patients treated with ketoprofen than in those
      receiving placebo (31.2% +/- 30.3% [95% confidence interval: 28.0-34.4] vs 25.5%
      +/- 31.2% [95% confidence interval: 22.1-28.8]; P = .020). However, the actual
      difference of the mean pain intensity scale between the 2 groups was small at the
      end of treatment. The frequency of adverse events was similar in both groups. The
      ketoprofen patch was more effective than placebo for relieving persistent local
      joint pain in patients with rheumatoid arthritis. The patch was also safe and
      well tolerated during the 2-week treatment period.

PMID- 20133511
TI  - Lack of a pharmacokinetic interaction between oral treprostinil and bosentan in
      healthy adult volunteers.
AB  - Treprostinil diethanolamine is an oral prostacyclin analog currently being
      evaluated for the treatment of pulmonary arterial hypertension (PAH).
      Treprostinil is metabolized primarily by cytochrome P450 (CYP) 2C8 with minor
      contribution from CYP2C9. It is expected that oral treprostinil will be
      administered with bosentan, approved for the treatment of PAH and known to induce
      CYP2C9 and 3A4. This study evaluated whether a drug interaction exists between
      oral treprostinil, bosentan, and its active metabolite Ro 48-5033 during co
      administration. Twenty-four participants were randomized in a 3-way crossover
      study to oral treprostinil 1 mg twice daily, bosentan 125 mg twice daily, and
      oral treprostinil 1 mg twice daily and bosentan 125 mg twice daily. Treprostinil
      geometric mean ratios (GMRs) (90% confidence interval [CIs]) for steady-state
      AUC(0-12) and C(max) (combination/treprostinil) were 0.92 (0.83, 1.03) and 0.96
      (0.83, 1.11), respectively, whereas bosentan GMRs (combination/bosentan) were
      1.02 (0.95, 1.10) and 1.04 (0.94, 1.15), respectively, and Ro 48-5033 GMRs were
      0.99 (0.93, 1.06) and 1.03 (0.94, 1.13). In conclusion, because the GMR and 90%
      CI are within the equivalence interval of 0.8 to 1.25, co-administration of oral
      treprostinil and bosentan did not result in a pharmacokinetic interaction for
      either agent.

PMID- 20133512
TI  - Left atrial strain and strain rate in patients with paroxysmal and persistent
      atrial fibrillation: relationship to left atrial structural remodeling detected
      by delayed-enhancement MRI.
AB  - BACKGROUND: Atrial fibrillation (AF) is a progressive condition that begins with
      hemodynamic and/or structural changes in the left atrium (LA) and evolves through
      paroxysmal and persistent stages. Because of limitations with current noninvasive
      imaging techniques, the relationship between LA structure and function is not
      well understood. METHODS AND RESULTS: Sixty-five patients (age, 61.2+/-14.2
      years; 67% men) with paroxysmal (44%) or persistent (56%) AF underwent 3D delayed
      enhancement MRI. Segmentation of the LA wall was performed and degree of
      enhancement (fibrosis) was determined using a semiautomated quantification
      algorithm. Two-dimensional echocardiography and longitudinal LA strain and strain
      rate during ventricular systole with velocity vector imaging were obtained. Mean
      fibrosis was 17.8+/-14.5%. Log-transformed fibrosis values correlated inversely
      with LA midlateral strain (r=-0.5, P=0.003) and strain rate (r=-0.4, P<0.005).
      Patients with persistent AF as compared with paroxysmal AF had more fibrosis
      (22+/-17% versus 14+/-9%, P=0.04) and lower midseptal (27+/-14% versus 38+/-16%,
      P=0.01) and midlateral (35+/-16% versus 45+/-14% P=0.03) strains. Multivariable
      stepwise regression showed that midlateral strain (r=-0.5, P=0.006) and strain
      rate (r=-0.4, P=0.01) inversely predicted the extent of fibrosis independent of
      other echocardiographic parameters and the rhythm during imaging. CONCLUSIONS: LA
      wall fibrosis by delayed-enhancement MRI is inversely related to LA strain and
      strain rate, and these are related to the AF burden. Echocardiographic assessment
      of LA structural and functional remodeling is quick and feasible and may be
      helpful in predicting outcomes in AF.

PMID- 20133513
TI  - Mesiodistal angulations of the mandibular canines, premolars and molars with or
      without the presence of third molars.
AB  - SUMMARY: The purpose of the present research was to compare the normal average
      values of mesiodistal axial angulation, with the mesiodistal axial angulation of
      canines, premolars and mandibular molars in individuals with and without the
      presence of the mandibular third molars. Panoramic radiographs of 19 male and 21
      female Caucasians, with a mean age of 22.35 years, who had not undergone
      orthodontic treatment were studied. The subjects were divided into two groups:
      group I, 20 radiographs of subjects without, and group II, 20 radiographs of
      subjects with mandibular third molars. The mean values of the groups were
      compared using a Student's t-test. The results show that, in both groups, the
      mandibular premolars and molars had enhanced angulation in the mesial direction,
      when compared with a control group of 42 Caucasians ranging in age from 12 to 17
      years with a 'normal' occlusion (P < 0.05), while the mesiodistal axial
      angulation of the mandibular canines was similar to the control group (P < 0.05).
      The two groups, when compared, exhibited similar angular values for the canines,
      premolars and mandibular molars (P < 0.05), indicating no influence of the third
      molars.

PMID- 20133514
TI  - Assessed facial normality after Twin Block therapy.
AB  - SUMMARY: The first aim of this study was to identify any difference in the
      perception of facial normality between orthodontists and lay people of patients
      with the initial presentation of a Class II division 1 malocclusion, the second
      is to investigate whether there was an identifiable facial change following Twin
      Block (TB) therapy, and lastly, the relationship between identifiable facial
      change and clinical measurements was explored. Animated laser scans of 16
      randomly selected adolescent patients, nine males aged 12-14 years and seven
      females aged 11-13 years with Class II division 1 malocclusions before and after
      TB therapy, were assessed on a visual analogue scale (VAS) by 34 orthodontists
      and 35 lay people. The 'Mark and Measure' and 'Orientated' techniques were used
      to determine soft tissue dimensions. Overjet was also recorded. Non-parametric
      statistical analyses were employed, including Mann-Whitney, Wilcoxon signed
      value, and Spearman's rank-order correlation tests. There was no statistically
      significant difference in facial normality scores of adolescents before TB
      therapy when assessed by orthodontists (46.2 mm) and lay people (50.9 mm; P =
      0.120). However, TB therapy significantly improved the assessment score of the
      orthodontists (54.8 mm) and lay people (57.8 mm; P = 0.000). Using a 5 per cent
      threshold in categorization of change in VAS scores, the majority of assessors
      perceived an overall 'improvement' (87.0 per cent). An increase in soft tissue
      lower face height (ST LFH) and overjet reduction was strongly correlated with the
      higher assessments of lay people (r = 0.515) and orthodontists (r = -0.505),
      respectively. Although orthodontists and lay people assess facial normality of
      patients with Class II division 1 malocclusions similarly, following TB therapy
      an increase in ST LFH with lay people and overjet reduction with orthodontists
      were most closely related to improved facial normality.

PMID- 20133515
TI  - Physical activity and albuminuria.
AB  - Higher urinary albumin excretion predicts future cardiovascular disease,
      hypertension, and chronic kidney disease. Physical activity improves endothelial
      function so activity may reduce albuminuria. Among diabetics, physical activity
      decreases albuminuria. In nondiabetics, prior studies have shown no association.
      The authors explored the cross-sectional association between physical activity
      and albuminuria in 3,587 nondiabetic women in 2 US cohorts, the Nurses' Health
      Study I in 2000 and the Nurses' Health Study II in 1997. Physical activity was
      expressed as metabolic equivalents per week. The outcome was the top
      albumin/creatinine ratio (ACR) decile. Multivariate logistic regression was used.
      Secondary analyses explored the ACR association with strenuous activity and
      walking. The mean age was 58.6 years. Compared with women in the lowest physical
      activity quintile, those in the highest quintile had a multivariate-adjusted odds
      ratio for the top ACR decile of 0.65 (95% confidence interval (CI): 0.46, 0.93).
      The multivariate-adjusted odds ratio for the top ACR decile for those with
      greater than 210 minutes per week of strenuous activity compared with no
      strenuous activity was 0.61 (95% CI: 0.37, 0.99), and for those in the highest
      quintile of walking compared with the lowest quintile, it was 0.69 (95% CI: 0.47,
      1.02). Greater physical activity is associated with a lower ACR in nondiabetic
      women.

PMID- 20133516
TI  - Estimating model-adjusted risks, risk differences, and risk ratios from complex
      survey data.
AB  - There is increasing interest in estimating and drawing inferences about risk or
      prevalence ratios and differences instead of odds ratios in the regression
      setting. Recent publications have shown how the GENMOD procedure in SAS (SAS
      Institute Inc., Cary, North Carolina) can be used to estimate these parameters in
      non-population-based studies. In this paper, the authors show how model-adjusted
      risks, risk differences, and risk ratio estimates can be obtained directly from
      logistic regression models in the complex sample survey setting to yield
      population-based inferences. Complex sample survey designs typically involve some
      combination of weighting, stratification, multistage sampling, clustering, and
      perhaps finite population adjustments. Point estimates of model-adjusted risks,
      risk differences, and risk ratios are obtained from average marginal predictions
      in the fitted logistic regression model. The model can contain both continuous
      and categorical covariates, as well as interaction terms. The authors use the
      SUDAAN software package (Research Triangle Institute, Research Triangle Park,
      North Carolina) to obtain point estimates, standard errors (via linearization or
      a replication method), confidence intervals, and P values for the parameters and
      contrasts of interest. Data from the 2006 National Health Interview Survey are
      used to illustrate these concepts.

PMID- 20133517
TI  - Birth weight and the risk of cardiovascular disease in the maternal grandparents.
AB  - Pregnancy complications and cardiovascular disease share some common
      determinants. It has previously been hypothesized that family history of
      cardiovascular disease would be associated with low birth weight. Records from
      120,317 Scottish births, 1992-2006, were linked to hospital admission and death
      certificate data for 71,681 pairs of maternal grandparents. There was a negative
      relation between the birth weight of the baby and the risk of either
      grandparent's experiencing ischemic heart disease (for a 1-kg increase in birth
      weight, hazard ratio = 0.86, 95% confidence interval: 0.83, 0.89) or
      cerebrovascular disease (hazard ratio = 0.82, 95% confidence interval: 0.77,
      0.87). Further analysis demonstrated that the associations were explained by
      increased risks of both delivering a small-for-gestational-age infant and
      delivering preterm among women whose parents had experienced cardiovascular
      disease. Adjustment for the mother's characteristics at the time of the birth
      attenuated the relation, but significant associations persisted: With a 1-kg
      increase in birth weight, the adjusted hazard ratio for ischemic heart disease =
      0.93 (95% confidence interval: 0.89, 0.96) and for cerebrovascular disease = 0.93
      (95% confidence interval: 0.89, 0.96). Familial aggregation of common
      determinants of pregnancy complications and cardiovascular disease is the likely
      explanation for the relation between an infant's birth weight and the risk of
      cardiovascular disease in other family members.

PMID- 20133518
TI  - Socioeconomic status and incidence of type 2 diabetes: results from the Black
      Women's Health Study.
AB  - The authors examined the relation between individual and neighborhood
      socioeconomic status (SES) and type 2 diabetes incidence among African-American
      women in the prospective Black Women's Health Study. Participants have completed
      mailed biennial follow-up questionnaires since 1995. US Census block group
      characteristics were used to measure neighborhood SES. Incidence rate ratios were
      estimated in clustered survival regression models. During 12 years of follow-up
      of 46,382 participants aged 30-69 years, 3,833 new cases of type 2 diabetes
      occurred. In models that included both individual and neighborhood SES factors,
      incidence rate ratios were 1.28 (95% confidence interval: 1.15, 1.43) for < or =
      12 years of education relative to > or = 17 years, 1.57 (95% confidence interval:
      1.30, 1.90) for household income <$15,000 relative to >$100,000, and 1.65 (95%
      confidence interval: 1.46, 1.85) for lowest quintile of neighborhood SES relative
      to highest. The associations were attenuated after adjustment for body mass
      index, suggesting it is the key intermediate factor in the pathway between SES
      and diabetes. The association of neighborhood SES with diabetes incidence was
      present even among women who were more educated and had a higher family income.
      Efforts to reduce the alarming rate of diabetes in African-American women must
      focus on both individual lifestyle changes and structural changes in
      disadvantaged neighborhoods.

PMID- 20133519
TI  - The emergency medical services safety attitudes questionnaire.
AB  - To characterize safety culture in emergency medical services (EMS), the authors
      modified a validated safety culture instrument, the Safety Attitudes
      Questionnaire (SAQ). The pilot instrument was administered to 3 EMS agencies in a
      large metropolitan area. The authors characterized safety culture across 6
      domains: safety climate, teamwork climate, perceptions of management, job
      satisfaction, working conditions, and stress recognition. The feasibility of
      characterizing safety culture in EMS was evaluated by examining response rate,
      item missingness, EMS chief administrators' perceptions of the EMS-SAQ, as well
      as psychometric properties.The results confirm feasibility with a high response
      rate, acceptable internal consistency, and model fit validity. However, some
      agencies voiced concerns about respondent burden and the wording and face
      validity of several EMS-SAQ items. Variation in safety culture scores across EMS
      agencies within a single geographic area, as well as variation across respondent
      characteristics, warrants further investigation.

PMID- 20133520
TI  - NMR structure determination for larger proteins using backbone-only data.
AB  - Conventional protein structure determination from nuclear magnetic resonance data
      relies heavily on side-chain proton-to-proton distances. The necessary side-chain
      resonance assignment, however, is labor intensive and prone to error. Here we
      show that structures can be accurately determined without nuclear magnetic
      resonance (NMR) information on the side chains for proteins up to 25 kilodaltons
      by incorporating backbone chemical shifts, residual dipolar couplings, and amide
      proton distances into the Rosetta protein structure modeling methodology. These
      data, which are too sparse for conventional methods, serve only to guide
      conformational search toward the lowest-energy conformations in the folding
      landscape; the details of the computed models are determined by the physical
      chemistry implicit in the Rosetta all-atom energy function. The new method is not
      hindered by the deuteration required to suppress nuclear relaxation processes for
      proteins greater than 15 kilodaltons and should enable routine NMR structure
      determination for larger proteins.

PMID- 20133521
TI  - Plumage color patterns of an extinct dinosaur.
AB  - For as long as dinosaurs have been known to exist, there has been speculation
      about their appearance. Fossil feathers can preserve the morphology of color
      imparting melanosomes, which allow color patterns in feathered dinosaurs to be
      reconstructed. Here, we have mapped feather color patterns in a Late Jurassic
      basal paravian theropod dinosaur. Quantitative comparisons with melanosome shape
      and density in extant feathers indicate that the body was gray and dark and the
      face had rufous speckles. The crown was rufous, and the long limb feathers were
      white with distal black spangles. The evolution of melanin-based within-feather
      pigmentation patterns may coincide with that of elongate pennaceous feathers in
      the common ancestor of Maniraptora, before active powered flight. Feathers may
      thus have played a role in sexual selection or other communication.

PMID- 20133522
TI  - Reconstructing past seawater Mg/Ca and Sr/Ca from mid-ocean ridge flank calcium
      carbonate veins.
AB  - Proxies for past seawater chemistry, such as Mg/Ca and Sr/Ca ratios, provide a
      record of the dynamic exchanges of elements between the solid Earth, the
      atmosphere, and the hydrosphere and the evolving influence of life. We estimated
      past oceanic Mg/Ca and Sr/Ca ratios from suites of 1.6- to 170-million-year-old
      calcium carbonate veins that had precipitated from seawater-derived fluids in
      ocean ridge flank basalts. Our data indicate that before the Neogene, oceanic
      Mg/Ca and Sr/Ca ratios were lower than in the modern ocean. Decreased ocean
      spreading since the Cretaceous and the resulting slow reduction in ocean crustal
      hydrothermal exchange throughout the early Tertiary may explain the recent rise
      in these ratios.

PMID- 20133523
TI  - Regulation of alternative splicing by histone modifications.
AB  - Alternative splicing of pre-mRNA is a prominent mechanism to generate protein
      diversity, yet its regulation is poorly understood. We demonstrated a direct role
      for histone modifications in alternative splicing. We found distinctive histone
      modification signatures that correlate with the splicing outcome in a set of
      human genes, and modulation of histone modifications causes splice site
      switching. Histone marks affect splicing outcome by influencing the recruitment
      of splicing regulators via a chromatin-binding protein. These results outline an
      adaptor system for the reading of histone marks by the pre-mRNA splicing
      machinery.

PMID- 20133524
TI  - Retromer is required for apoptotic cell clearance by phagocytic receptor
      recycling.
AB  - The cell surface receptor CED-1 mediates apoptotic cell recognition by phagocytic
      cells, enabling cell corpse clearance in Caenorhabditis elegans. Here, we found
      that the C. elegans intracellular protein sorting complex, retromer, was required
      for cell corpse clearance by mediating the recycling of CED-1. Retromer was
      recruited to the surfaces of phagosomes containing cell corpses, and its loss of
      function caused defective cell corpse removal. The retromer probably acted
      through direct interaction with CED-1 in the cell corpse recognition pathway. In
      the absence of retromer function, CED-1 associated with lysosomes and failed to
      recycle from phagosomes and cytosol to the plasma membrane. Thus, retromer is an
      essential mediator of apoptotic cell clearance by regulating phagocytic
      receptor(s) during cell corpse engulfment.

PMID- 20133525
TI  - New drug and biological product approvals, 2009.

PMID- 20133526
TI  - FDA approves tocilizumab to treat rheumatoid arthritis.

PMID- 20133528
TI  - EPA eyes unused pharmaceuticals.

PMID- 20133529
TI  - Improving processes for blood factor products: from blood bank to hospital
      pharmacy.

PMID- 20133530
TI  - Intrapericardial triamcinolone for acute pericarditis after electrophysiologic
      procedures.
AB  - PURPOSE: The use of intrapericardial triamcinolone for acute pericarditis after
      electrophysiologic procedures in three patients is described. SUMMARY: Treatment
      for idiopathic pericarditis and viral pericarditis, which account for about 85%
      of cases, focuses on pain management and decreasing pericardial inflammation.
      This is oftentimes achieved with nonsteroidal antiinflammatory drugs (NSAIDs).
      Colchicine may be used in combination with NSAIDs, specifically in postmyocardial
      infarction pericarditis and recurrent pericarditis. Because oral corticosteroid
      use has been shown to be an independent risk factor in pericarditis recurrence,
      their use in patients with refractory pericarditis is reserved as a last-resort
      option. Intrapericardial triamcinolone is an uncommon treatment approach,
      although it is recommended in select situations of pericarditis according to
      guidelines developed by the European Society of Cardiology. In this retrospective
      case series, three patients with pericarditis, tamponade, or both as a
      complication of radiofrequency ablation or implantable cardioverter defibrillator
      implantation received triamcinolone. The drug was instilled intrapericardially,
      with doses ranging from 50 to 200 mg. In two patients, the need for pain
      medication and the perceived pain score decreased dramatically after
      triamcinolone administration. In the third patient, triamcinolone administration
      decreased the need for supportive therapy but was not deemed a complete clinical
      success. Additional study is necessary to better define the use of
      intrapericardial triamcinolone and determine long-term outcomes associated with
      this therapy. Other factors, including past medical history and renal function,
      also need to be taken into account when choosing the proper dosing regimen.
      CONCLUSION: Intrapericardial administration of triamcinolone acetonide may be an
      effective treatment for patients with acute pericarditis after electrophysiologic
      procedures.

PMID- 20133531
TI  - Estimating aminoglycoside clearance and creatinine clearance in underweight
      patients.
AB  - PURPOSE: An adjustment factor (AF) was developed and evaluated to determine the
      best method for estimating aminoglycoside clearance (CL(amino)) and creatinine
      clearance (CL(cr)) in underweight patients. METHODS: This study was a
      retrospective, multicenter, chart analysis of aminoglycoside pharmacokinetic data
      obtained between January 2000 and August 2006 at the University of Southern
      California University Hospital and Cedars-Sinai Medical Center. Adult patients
      were included in this study if they had received inpatient aminoglycoside
      therapy, were at least 60 inches tall, and were at least 10% below their ideal
      body weight (IBW). CL(cr) and CL(amino) were estimated and compared to actual
      CL(amino) using the Cockcroft-Gault equation with actual serum creatinine (SCr)
      (CG(SCr)), Cockcroft-Gault equation with SCr rounded to 1 mg/dL (CG(rnd)), and
      Cockcroft-Gault equation multiplied by an AF (CG(AF)). Results An AF of 0.69 was
      determined from 52 patients and tested in 53 separate patients. The CG(AF) method
      was more precise and less biased than the CG(SCr) equation; the CG(rnd) equation
      was less biased than the CG(SCr) equation; the CG(AF) method was more precise and
      less biased than the CG(rnd) equation, but this difference was not statistically
      significant. In underweight patients with an SCr concentration of > or = 1 mg/dL,
      the CG(AF) method had less bias compared with the CG(SCr) equation. CONCLUSION:
      Both the CG(rnd) and CG(AF) methods of predicting CL(amino) in underweight
      patients were superior to the CG(SCr) equation. The CG(AF) method was more
      accurate in patients exhibiting greater differences between IBW and actual body
      weight.

PMID- 20133532
TI  - Automated endotoxin testing program for high-risk-level compounded sterile
      preparations at an institutional compounding pharmacy.
AB  - PURPOSE: An endotoxin testing program for high-risk-level compounded sterile
      preparations (CSPs) was verified for compliance with finished-preparation release
      test requirements of United States Pharmacopeia chapter 797 and implemented at an
      institutional compounding pharmacy. SUMMARY: An efficient bacterial endotoxins
      test (BET) was sought for finished-preparation testing of high-risk-level CSPs
      prepared in batches of > or =25 units. An automated photometric BET was selected
      that utilized dried, pre-calibrated Limulus amebocyte lysate cartridges rather
      than liquid reagents and standards. Endotoxin testing began after verifying test
      conditions for each CSP and approving a standard procedure for training BET
      analysts and maintaining uniform methodology. A pharmacopeial endotoxin limit and
      limit dilution were determined for each CSP. The majority of CSPs included
      patient-controlled analgesia solutions, epidural analgesia solutions, and
      cardioplegia solutions. BET conditions were verified by measuring the recovery of
      endotoxin positive controls in sterile water dilutions for each CSP. Cardioplegia
      solutions met an endotoxin limit of 0.5 EU/mL, and epidural bags had an
      intrathecal endotoxin limit of 0.05 EU/mL. All other CSPs had detection limits
      well within compendial requirements. All test results collected during the first
      year of implementation were pyrogen free, which provided compelling evidence of
      appropriate application of aseptic technique, appropriate selection of equipment
      and methods, and the nonpyrogenic quality of powders used in compounding at the
      pharmacy. CONCLUSION: A photometric endotoxins test that met all requirements of
      the BET was verified and implemented for high-risk-level CSPs prepared in an
      institutional pharmacy.

PMID- 20133533
TI  - Stability of extemporaneously prepared rifaximin oral suspensions.
AB  - PURPOSE: The stability of extemporaneously prepared rifaximin oral suspensions
      was studied. METHODS: An oral suspension of rifaximin 20 mg/mL was prepared by
      thoroughly grinding six 200-mg tablets of rifaximin in a glass mortar. Thirty
      milliliters of Ora-Plus and 30 mL of either Ora-Sweet or Ora-Sweet SF were mixed
      and added to the powder to make a final volume of 60 mL. Three identical samples
      of each formulation were prepared and placed in 2-oz amber plastic bottles with
      child-resistant caps and were stored at room temperature (23-25 degrees C). A 1
      mL sample was withdrawn from each of the six bottles with a micropipette
      immediately after preparation and at 7, 15, 30, and 60 days. After further
      dilution to an expected concentration of 20 microg/mL with mobile phase, the
      samples were assayed in duplicate using stability-indicating high-performance
      liquid chromatography. The samples were visually examined for any color change
      and pH was tested on each day of analysis. Stability was determined by evaluating
      the percentage of the initial concentration remaining at each time point and
      defined as retention of at least 90% of the initial concentration of rifaximin.
      RESULTS: At least 99% of the initial rifaximin remained throughout the 60-day
      study period in both preparations. There were no detectable changes in color,
      odor, taste, or pH and no visible microbial growth in any sample. CONCLUSION:
      Extemporaneously prepared suspensions of rifaximin 20 mg/mL in 1:1 mixtures of
      Ora-Plus with either Ora-Sweet or Ora-Sweet SF were stable for at least 60 days
      when stored in 2-oz amber plastic bottles at room temperature.

PMID- 20133534
TI  - Influence of pharmacist intervention on prescribing of angiotensin-converting
      enzyme inhibitors, angiotensin II-receptor blockers, and aspirin for diabetic
      patients.
AB  - PURPOSE: The influence of pharmacist intervention on the prescribing of
      angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II-receptor blockers
      (ARBs), and aspirin for patients with diabetes was evaluated. METHODS: A
      retrospective chart review was performed for diabetic patients seen in a family
      medicine clinic. Patients were included in the analyses if they were 18-88 years
      old, had a diagnosis of type 1 or type 2 diabetes, had been seen in the family
      medicine clinic between July 2006 and October 2008, and had received a
      consultation by pharmacy services. All selected charts were reviewed to assess
      appropriate use of ACE inhibitor, ARB, and aspirin therapy, as recommended by
      American Diabetes Association (ADA) guidelines, before and after pharmacist
      intervention. Typical pharmacist interventions consisted of direct consultation
      with the prescriber and therapeutic education sessions conducted by pharmacy
      personnel. All patients were seen and evaluated by pharmacy personnel before
      meeting with the prescriber. RESULTS: Before pharmacist intervention, 41 (59%) of
      70 patients were receiving appropriate ACE inhibitor or ARB therapy and 24 (34%)
      of 71 patients were receiving appropriate aspirin therapy as recommended by ADA.
      After pharmacist intervention, 63 (90%) of 70 patients were receiving appropriate
      ACE inhibitor or ARB therapy and 48 (68%) of 71 patients were receiving
      appropriate aspirin therapy as recommended by ADA (p < 0.0001 for both
      differences). CONCLUSION: A pharmacy intervention program in a primary care
      setting was associated with a significant increase in prescriber adherence to ADA
      guidelines for ACE inhibitor or ARB therapy and for aspirin therapy in diabetic
      patients.

PMID- 20133535
TI  - Drug costs and utilization after implementation of a posaconazole prophylaxis
      protocol in adults with acute myelogenous leukemia.
AB  - PURPOSE: Drug costs and utilization after implementation of a posaconazole
      prophylaxis protocol in adults with acute myelogenous leukemia (AML) were
      studied. METHODS: Adult patients who initiated induction or reinduction
      chemotherapy for the treatment of AML between December 1, 2006, and March 31,
      2008, at a tertiary care hospital were included in this retrospective cohort
      study. Patients were divided into two groups: preprotocol (treated before June 1,
      2007) and postprotocol (treated on or after June 1, 2007). Medical charts,
      including pharmacy and laboratory data, were reviewed for all patients. Outcomes
      measured included antifungal and antibacterial drug costs and utilization and
      total pharmacy costs. RESULTS: A total of 66 patients were evaluated (33 in each
      group). Baseline characteristics, except patient age, were similar between
      groups. Each group incurred similar costs and utilized resources for similar
      periods of time as evidenced by similar lengths of stay, duration of neutropenia,
      and mortality. Antibacterial costs, total pharmacy costs, and other utilization
      outcomes were also similar between the two groups. Alterations to antifungal
      management strategy occurred more often in the postprotocol group (33% versus
      58%, p = 0.048). CONCLUSION: Implementation of a posaconazole protocol did not
      significantly alter antifungal or antibacterial drug costs or utilization or
      total pharmacy costs. Prophylactic posaconazole was frequently changed to
      alternative antifungal therapy due to an adverse drug event, perceived lack of
      efficacy, avoidance of a drug interaction, or inability to tolerate oral intake.

PMID- 20133536
TI  - Effective use of workload and productivity monitoring tools in health-system
      pharmacy, part 1.
AB  - PURPOSE: The current status of external and internal workload and productivity
      measurement systems and strategies to improve their use to maximize overall
      pharmacy department operational performance and staffing effectiveness are
      described. SUMMARY: The use of operational benchmarking is increasing within
      health systems as a tool for continuously measuring and improving departmental
      performance and evaluating departmental success. Unfortunately, software used for
      benchmarking purposes is available through a limited number of commercial vendors
      and consultants, and these systems are unable to effectively measure department
      operations and overall performance. The theoretical value of benchmarking and
      productivity measurement systems, including a description of the various
      definitions, tools, and data sources for comparing pharmacy productivity data, is
      summarized. The limitations of commercially available vendor productivity
      monitoring systems and desired strategies for improving their use are also
      reviewed. Preferred productivity and cost metrics for measuring pharmacy
      department effectiveness are suggested, and strategies for obtaining value from
      external and internal productivity monitoring systems are explored. CONCLUSION:
      Challenges with external operational benchmarking and internal productivity
      monitoring systems are numerous. These systems rarely measure the quality of
      pharmacy services provided and their effect on patient care outcomes and the
      total cost of care. Benchmarking vendors must modernize their software and
      develop internal checks to confirm data integrity in order to make their products
      more useful and reliable. In addition, data supporting the patient care role of
      the pharmacist should be integrated into all productivity monitoring systems and
      be used to demonstrate the positive impact of pharmacy services on the total cost
      and quality of patient care.

PMID- 20133537
TI  - An employer-based, pharmacist intervention model for patients with type 2
      diabetes.
AB  - PURPOSE: Changes in glycosylated hemoglobin (HbA(1c)) levels, blood pressure
      measurements, and utilization metrics among diabetic patients managed by a
      clinical pharmacist were studied. SUMMARY: This pharmacist intervention model was
      developed by Polk County, Florida, to engage patients with diabetes in managing
      their health based on the Asheville Project's framework. The diabetes program was
      implemented in February 2005, with an on-site clinical pharmacist to counsel
      participants with diabetes. The on-site pharmacist individualized each patient's
      care. After the initial assessment, educational deficiencies were noted and
      addressed as needed. Outcomes measured included changes in HbA(1c), blood
      glucose, and blood pressure values and utilization metrics, such as
      hospitalization and emergency room visit rates, from baseline to one year after
      pharmacist intervention. Of the 564 participants who enrolled in the program, 477
      were enrolled at the end of one year and were included in the analysis. Results
      showed that HbA(1c) values steadily decreased over the one-year study period. At
      baseline, there were 55% of participants with an average HbA(1c) value of < or
      =7%. After one year, 72% of participants had HbA(1c) values of < or =7%.
      Participants' mean systolic and diastolic blood pressure values were lower at the
      end of one year compared with the baseline. Participants also had a 30% reduction
      in hospital admissions, and the number of emergency room visits during the one
      year period decreased by 24%. CONCLUSION: An employer-based pharmacist
      intervention model for patients with diabetes improved HbA(1c) levels, reduced
      systolic and diastolic blood pressure values, and decreased hospitalizations and
      emergency room visits after one year.

PMID- 20133538
TI  - Detecting adverse drug events through data mining.

PMID- 20133539
TI  - Ensuring integrity in science.

PMID- 20133540
TI  - U.S. budget. Science spared from domestic spending freeze--for now.

PMID- 20133541
TI  - U.S. budget. Obama shakes up satellite programs for clearer picture of Earth.

PMID- 20133542
TI  - Research facilities. New Korean science city caught in political crossfire.

PMID- 20133544
TI  - Scientific publishing. Publications and expats warn of Russia's dangerous
      decline.

PMID- 20133545
TI  - Conservation. Big battle brewing over elephants at upcoming CITES meeting.

PMID- 20133547
TI  - Evolution. 'Toadness' a key feature for global spread of these amphibians.

PMID- 20133548
TI  - Relief among the rubble.

PMID- 20133549
TI  - The long battle against a horrific disease.

PMID- 20133550
TI  - Rebuilding. From the bottom up.

PMID- 20133551
TI  - Agroforestry. Greening Haiti, tree by tree.

PMID- 20133552
TI  - Savannas need protection.

PMID- 20133553
TI  - Religiosity tied to socioeconomic status.

PMID- 20133554
TI  - Predators could help save pollock.

PMID- 20133555
TI  - Taking our lumps.

PMID- 20133556
TI  - Comment on "Unexpected epoxide formation in the gas-phase photooxidation of
      isoprene".
AB  - Paulot et al. (Reports, 7 August 2009, p. 730) reported that the photooxidation
      of isoprene under low-nitrogen oxides (NOx) conditions produces epoxides that can
      facilitate the formation of secondary organic aerosol (SOA). However, another
      pathway involving the formation of methyl-butenediol intermediates can also lead
      to isoprene-derived SOA formation. Further research is needed to clarify the fate
      of isoprene in the atmosphere.

PMID- 20133558
TI  - Ethics. Gene doping and sport.

PMID- 20133559
TI  - Evolution. Tinkering inside the organelle.

PMID- 20133560
TI  - Physics. Splitting spin states on a chip.

PMID- 20133561
TI  - Physics. Seeing quantum fractals.

PMID- 20133562
TI  - Biochemistry. An ensemble view of allostery.

PMID- 20133563
TI  - Oceans. Iron and the carbon pump.

PMID- 20133565
TI  - 100-GHz transistors from wafer-scale epitaxial graphene.
AB  - The high carrier mobility of graphene has been exploited in field-effect
      transistors that operate at high frequencies. Transistors were fabricated on
      epitaxial graphene synthesized on the silicon face of a silicon carbide wafer,
      achieving a cutoff frequency of 100 gigahertz for a gate length of 240
      nanometers. The high-frequency performance of these epitaxial graphene
      transistors exceeds that of state-of-the-art silicon transistors of the same gate
      length.

PMID- 20133564
TI  - Development of monocytes, macrophages, and dendritic cells.
AB  - Monocytes and macrophages are critical effectors and regulators of inflammation
      and the innate immune response, the immediate arm of the immune system. Dendritic
      cells initiate and regulate the highly pathogen-specific adaptive immune
      responses and are central to the development of immunologic memory and tolerance.
      Recent in vivo experimental approaches in the mouse have unveiled new aspects of
      the developmental and lineage relationships among these cell populations. Despite
      this, the origin and differentiation cues for many tissue macrophages, monocytes,
      and dendritic cell subsets in mice, and the corresponding cell populations in
      humans, remain to be elucidated.

PMID- 20133566
TI  - Visualizing critical correlations near the metal-insulator transition in Ga(1
      x)Mn(x)As.
AB  - Electronic states in disordered conductors on the verge of localization are
      predicted to exhibit critical spatial characteristics indicative of the proximity
      to a metal-insulator phase transition. We used scanning tunneling microscopy to
      visualize electronic states in Ga(1-x)Mn(x)As samples close to this transition.
      Our measurements show that doping-induced disorder produces strong spatial
      variations in the local tunneling conductance across a wide range of energies.
      Near the Fermi energy, where spectroscopic signatures of electron-electron
      interaction are the most prominent, the electronic states exhibit a diverging
      spatial correlation length. Power-law decay of the spatial correlations is
      accompanied by log-normal distributions of the local density of states and
      multifractal spatial characteristics.

PMID- 20133567
TI  - A coherent beam splitter for electronic spin states.
AB  - Rapid coherent control of electron spin states is required for implementation of
      a spin-based quantum processor. We demonstrated coherent control of electronic
      spin states in a double quantum dot by sweeping an initially prepared spin
      singlet state through a singlet-triplet anticrossing in the energy-level
      spectrum. The anticrossing serves as a beam splitter for the incoming spin
      singlet state. When performed within the spin-dephasing time, consecutive
      crossings through the beam splitter result in coherent quantum oscillations
      between the singlet state and a triplet state. The all-electrical method for
      quantum control relies on electron-nuclear spin coupling and drives single
      electron spin rotations on nanosecond time scales.

PMID- 20133568
TI  - Water freezes differently on positively and negatively charged surfaces of
      pyroelectric materials.
AB  - Although ice melts and water freezes under equilibrium conditions at 0 degrees C,
      water can be supercooled under homogeneous conditions in a clean environment down
      to -40 degrees C without freezing. The influence of the electric field on the
      freezing temperature of supercooled water (electrofreezing) is of topical
      importance in the living and inanimate worlds. We report that positively charged
      surfaces of pyroelectric LiTaO3 crystals and SrTiO3 thin films promote ice
      nucleation, whereas the same surfaces when negatively charged reduce the freezing
      temperature. Accordingly, droplets of water cooled down on a negatively charged
      LiTaO3 surface and remaining liquid at -11 degrees C freeze immediately when this
      surface is heated to -8 degrees C, as a result of the replacement of the negative
      surface charge by a positive one. Furthermore, powder x-ray diffraction studies
      demonstrated that the freezing on the positively charged surface starts at the
      solid/water interface, whereas on a negatively charged surface, ice nucleation
      starts at the air/water interface.

PMID- 20133569
TI  - Gradual adaptation toward a range-expansion phenotype initiated the global
      radiation of toads.
AB  - Recent studies have identified range expansion as a potential driver of
      speciation. Yet it remains poorly understood how, under identical extrinsic
      settings, differential tendencies for geographic movement of taxa originate and
      subsequently affect diversification. We identified multiple traits that predict
      large distributional ranges in extant species of toads (Bufonidae) and used
      statistical methods to define and phylogenetically reconstruct an optimal range
      expansion phenotype. Our results indicate that lineage-specific range-shifting
      abilities increased through an accumulation of adaptive traits that culminated in
      such a phenotype. This initiated the episode of global colonization and triggered
      the major radiation of toads. Evolution toward a range-expansion phenotype might
      be crucial to understanding both ancient widespread radiations and the
      evolutionary background of contemporary invasive species such as the cane toad.

PMID- 20133570
TI  - Flight orientation behaviors promote optimal migration trajectories in high
      flying insects.
AB  - Many insects undertake long-range seasonal migrations to exploit temporary
      breeding sites hundreds or thousands of kilometers apart, but the behavioral
      adaptations that facilitate these movements remain largely unknown. Using
      entomological radar, we showed that the ability to select seasonally favorable,
      high-altitude winds is widespread in large day- and night-flying migrants and
      that insects adopt optimal flight headings that partially correct for crosswind
      drift, thus maximizing distances traveled. Trajectory analyses show that these
      behaviors increase migration distances by 40% and decrease the degree of drift
      from seasonally optimal directions. These flight behaviors match the
      sophistication of those seen in migrant birds and help explain how high-flying
      insects migrate successfully between seasonal habitats.

PMID- 20133571
TI  - Conformational spread as a mechanism for cooperativity in the bacterial flagellar
      switch.
AB  - The bacterial flagellar switch that controls the direction of flagellar rotation
      during chemotaxis has a highly cooperative response. This has previously been
      understood in terms of the classic two-state, concerted model of allosteric
      regulation. Here, we used high-resolution optical microscopy to observe switching
      of single motors and uncover the stochastic multistate nature of the switch. Our
      observations are in detailed quantitative agreement with a recent general model
      of allosteric cooperativity that exhibits conformational spread--the stochastic
      growth and shrinkage of domains of adjacent subunits sharing a particular
      conformational state. We expect that conformational spread will be important in
      explaining cooperativity in other large signaling complexes.

PMID- 20133572
TI  - Cryo-EM model of the bullet-shaped vesicular stomatitis virus.
AB  - Vesicular stomatitis virus (VSV) is a bullet-shaped rhabdovirus and a model
      system of negative-strand RNA viruses. Through direct visualization by means of
      cryo-electron microscopy, we show that each virion contains two nested, left
      handed helices: an outer helix of matrix protein M and an inner helix of
      nucleoprotein N and RNA. M has a hub domain with four contact sites that link to
      neighboring M and N subunits, providing rigidity by clamping adjacent turns of
      the nucleocapsid. Side-by-side interactions between neighboring N subunits are
      critical for the nucleocapsid to form a bullet shape, and structure-based
      mutagenesis results support this description. Together, our data suggest a
      mechanism of VSV assembly in which the nucleocapsid spirals from the tip to
      become the helical trunk, both subsequently framed and rigidified by the M layer.

PMID- 20133573
TI  - Abundance of ribosomal RNA gene copies maintains genome integrity.
AB  - The ribosomal RNA (rDNA) gene repeats are essential housekeeping genes found in
      all organisms. A gene amplification system maintains large cluster(s) of tandemly
      repeated copies in the chromosome, with each species having a specific number of
      copies. Yeast has many untranscribed rDNA copies (extra copies), and we found
      that when they are lost, the cells become sensitive to DNA damage induced by
      mutagens. We show that this sensitivity is dependent on rDNA transcriptional
      activity, which interferes with cohesion between rDNA loci of sister chromatids.
      The extra rDNA copies facilitate condensin association and sister-chromatid
      cohesion, thereby facilitating recombinational repair. These results suggest that
      high concentrations of heavily transcribed genes are toxic to the cells, and
      therefore amplified genes, such as rDNA, have evolved.

PMID- 20133574
TI  - Optimal localization by pointing off axis.
AB  - Is centering a stimulus in the field of view an optimal strategy to localize and
      track it? We demonstrated, through experimental and computational studies, that
      the answer is no. We trained echolocating Egyptian fruit bats to localize a
      target in complete darkness, and we measured the directional aim of their sonar
      clicks. The bats did not center the sonar beam on the target, but instead pointed
      it off axis, accurately directing the maximum slope ("edge") of the beam onto the
      target. Information-theoretic calculations showed that using the maximum slope is
      optimal for localizing the target, at the cost of detection. We propose that the
      tradeoff between detection (optimized at stimulus peak) and localization
      (optimized at maximum slope) is fundamental to spatial localization and tracking
      accomplished through hearing, olfaction, and vision.

PMID- 20133576
TI  - Astrocytic endfoot Ca2+ and BK channels determine both arteriolar dilation and
      constriction.
AB  - Neuronal activity is thought to communicate to arterioles in the brain through
      astrocytic calcium (Ca(2+)) signaling to cause local vasodilation. Paradoxically,
      this communication may cause vasoconstriction in some cases. Here, we show that,
      regardless of the mechanism by which astrocytic endfoot Ca(2+) was elevated,
      modest increases in Ca(2+) induced dilation, whereas larger increases switched
      dilation to constriction. Large-conductance, Ca(2+)-sensitive potassium channels
      in astrocytic endfeet mediated a majority of the dilation and the entire
      vasoconstriction, implicating local extracellular K(+) as a vasoactive signal for
      both dilation and constriction. These results provide evidence for a unifying
      mechanism that explains the nature and apparent duality of the vascular response,
      showing that the degree and polarity of neurovascular coupling depends on
      astrocytic endfoot Ca(2+) and perivascular K(+).

PMID- 20133577
TI  - Agrobacterium type IV secretion system and its substrates form helical arrays
      around the circumference of virulence-induced cells.
AB  - The genetic transformation of plant cells by Agrobacterium tumefaciens results
      from the transfer of DNA and proteins via a specific virulence (vir) -induced
      type IV secretion system (T4SS). To better understand T4SS function, we analyzed
      the localization of its structural components and substrates by deconvolution
      fluorescence microscopy. GFP fusions to T4SS proteins with cytoplasmic tails,
      VirB8 and VirD4, or cytoplasmic T4SS substrate proteins, VirD2, VirE2, and VirF,
      localize in a helical pattern of fluorescent foci around the perimeter of the
      bacterial cell. All fusion proteins were expressed at native levels of vir
      induction. Importantly, most fusion proteins are functional and do not exhibit
      dominant-negative effects on DNA transfer to plant cells. Further, GFP-VirB8
      complements a virB8 deletion strain. We also detect native VirB8 localization as
      a helical array of foci by immunofluorescence microscopy. T4SS foci likely use an
      existing helical scaffold during their assembly. Indeed, the bacterial
      cytoskeletal component MinD colocalizes with GFP-VirB8. Helical arrays of foci
      are found at all times investigated between 12 and 48 h post vir induction at 19
      degrees C. These data lead to a model with multiple T4SSs around the bacterial
      cell that likely facilitate host cell attachment and DNA transfer. In support, we
      find multiple T pili around vir-induced bacterial cells.

PMID- 20133578
TI  - X chromosome-wide analyses of genomic DNA methylation states and gene expression
      in male and female neutrophils.
AB  - The DNA methylation status of human X chromosomes from male and female
      neutrophils was identified by high-throughput sequencing of HpaII and MspI
      digested fragments. In the intergenic and intragenic regions on the X chromosome,
      the sites outside CpG islands were heavily hypermethylated to the same degree in
      both genders. Nearly half of X chromosome promoters were either hypomethylated or
      hypermethylated in both females and males. Nearly one third of X chromosome
      promoters were a mixture of hypomethylated and heterogeneously methylated sites
      in females and were hypomethylated in males. Thus, a large fraction of genes that
      are silenced on the inactive X chromosome are hypomethylated in their promoter
      regions. These genes frequently belong to the evolutionarily younger strata of
      the X chromosome. The promoters that were hypomethylated at more than two sites
      contained most of the genes that escaped silencing on the inactive X chromosome.
      The overall levels of expression of X-linked genes were indistinguishable in
      females and males, regardless of the methylation state of the inactive X
      chromosome. Thus, in addition to DNA methylation, other factors are involved in
      the fine tuning of gene dosage compensation in neutrophils.

PMID- 20133579
TI  - Spontaneous assembly and active disassembly balance adherens junction
      homeostasis.
AB  - The homeostasis of adherens junctions was studied using E-cadherin and its two
      mutants tagged by the photoconvertible protein Dendra2 in epithelial A-431 cells
      and in CHO cells lacking endogenous cadherin. The first mutant contained point
      mutations of two elements, Lys738 and the dileucine motif that suppressed
      cadherin endocytosis. The second mutant contained, in addition, an extensive
      truncation that uncoupled the mutant from beta-catenin and p120. Surprisingly,
      the intact cadherin and its truncated mutant were recruited into the junctions
      with identical kinetics. The full-size cadherin was actively removed from the
      junctions by a process that was unaffected by the inactivation of its endocytic
      elements. The cadherin's apparent half-residence time in the junction was about 2
      min. Cadherin clusters made of the truncated mutant exhibited much slower but ATP
      independent junctional turnover. Taken together, our experiments showed that
      adherens junction homeostasis consists of three distinctive steps: cadherin
      spontaneous recruitment, its lateral catenin-dependent association, and its
      active release from the resulting clusters. The latter process, whose mechanism
      is not clear, may play an important role in various kinds of normal and abnormal
      morphogenesis.

PMID- 20133580
TI  - Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent
      regulators of human papillomavirus oncogene expression.
AB  - An essential step in the pathogenesis of human papillomavirus (HPV)-associated
      cancers is the dysregulated expression of the viral oncogenes. The papillomavirus
      E2 protein can silence the long control region (LCR) promoter that controls viral
      E6 and E7 oncogene expression. The mechanisms by which E2 represses oncogene
      expression and the cellular factors through which E2 mediates this silencing are
      largely unknown. We conducted an unbiased, genome-wide siRNA screen and series of
      secondary screens that identified 96 cellular genes that contribute to the
      repression of the HPV LCR. In addition to confirming a role for the E2-binding
      bromodomain protein Brd4 in E2-mediated silencing, we identified a number of
      genes that have not previously been implicated in E2 repression, including the
      demethylase JARID1C/SMCX as well as EP400, a component of the NuA4/TIP60 histone
      acetyltransferase complex. Each of these genes contributes independently and
      additively to E2-mediated silencing, indicating that E2 functions through several
      distinct cellular complexes to repress E6 and E7 expression.

PMID- 20133581
TI  - Translation efficiency is determined by both codon bias and folding energy.
AB  - Synonymous mutations do not alter the protein produced yet can have a significant
      effect on protein levels. The mechanisms by which this effect is achieved are
      controversial; although some previous studies have suggested that codon bias is
      the most important determinant of translation efficiency, a recent study
      suggested that mRNA folding at the beginning of genes is the dominant factor via
      its effect on translation initiation. Using the Escherichia coli and
      Saccharomyces cerevisiae transcriptomes, we conducted a genome-scale study aiming
      at dissecting the determinants of translation efficiency. There is a significant
      association between codon bias and translation efficiency across all endogenous
      genes in E. coli and S. cerevisiae but no association between folding energy and
      translation efficiency, demonstrating the role of codon bias as an important
      determinant of translation efficiency. However, folding energy does modulate the
      strength of association between codon bias and translation efficiency, which is
      maximized at very weak mRNA folding (i.e., high folding energy) levels. We find a
      strong correlation between the genomic profiles of ribosomal density and genomic
      profiles of folding energy across mRNA, suggesting that lower folding energies
      slow down the ribosomes and decrease translation efficiency. Accordingly, we find
      that selection forces act near uniformly to decrease the folding energy at the
      beginning of genes. In summary, these findings testify that in endogenous genes,
      folding energy affects translation efficiency in a global manner that is not
      related to the expression levels of individual genes, and thus cannot be detected
      by correlation with their expression levels.

PMID- 20133582
TI  - Energetic basis of colonial living in social insects.
AB  - Understanding the ecology and evolution of insect societies requires greater
      knowledge of how sociality affects the performance of whole colonies. Metabolic
      scaling theory, based largely on the body mass scaling of metabolic rate, has
      successfully predicted many aspects of the physiology and life history of
      individual (or unitary) organisms. Here we show, using a diverse set of social
      insect species, that this same theory predicts the size dependence of basic
      features of the physiology (i.e., metabolic rate, reproductive allocation) and
      life history (i.e., survival, growth, and reproduction) of whole colonies. The
      similarity in the size dependence of these features in unitary organisms and
      whole colonies points to commonalities in functional organization. Thus, it
      raises an important question of how such evolutionary convergence could arise
      through the process of natural selection.

PMID- 20133583
TI  - Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA
      biogenesis in the ERGO-1/Argonaute pathway.
AB  - Argonaute (AGO) proteins interact with distinct classes of small RNAs to direct
      multiple regulatory outcomes. In many organisms, including plants, fungi, and
      nematodes, cellular RNA-dependent RNA polymerases (RdRPs) use AGO targets as
      templates for amplification of silencing signals. Here, we show that distinct
      RdRPs function sequentially to produce small RNAs that target endogenous loci in
      Caenorhabditis elegans. We show that DCR-1, the RdRP RRF-3, and the dsRNA-binding
      protein RDE-4 are required for the biogenesis of 26-nt small RNAs with a 5'
      guanine (26G-RNAs) and that 26G-RNAs engage the Piwi-clade AGO, ERGO-1. Our
      findings support a model in which targeting by ERGO-1 recruits a second RdRP (RRF
      1 or EGO-1), which in turn transcribes 22G-RNAs that interact with worm-specific
      AGOs (WAGOs) to direct gene silencing. ERGO-1 targets exhibit a nonrandom
      distribution in the genome and appear to include many gene duplications,
      suggesting that this pathway may control overexpression resulting from gene
      expansion.

PMID- 20133584
TI  - A membrane-associated thioredoxin required for plant growth moves from cell to
      cell, suggestive of a role in intercellular communication.
AB  - Thioredoxins (Trxs) are small ubiquitous regulatory disulfide proteins. Plants
      have an unusually complex complement of Trxs composed of six well-defined types
      (Trxs f, m, x, y, h, and o) that reside in different cell compartments and
      function in an array of processes. The extraplastidic h type consists of multiple
      members that in general have resisted isolation of a specific phenotype. In
      analyzing mutant lines in Arabidopsis thaliana, we identified a phenotype of
      dwarf plants with short roots and small yellowish leaves for AtTrx h9
      (henceforth, Trx h9), a member of the Arabidopsis Trx h family. Trx h9 was found
      to be associated with the plasma membrane and to move from cell to cell. Controls
      conducted in conjunction with the localization of Trx h9 uncovered another h-type
      Trx in mitochondria (Trx h2) and a Trx in plastids earlier described as a
      cytosolic form in tomato. Analysis of Trx h9 revealed a 17-amino acid N-terminal
      extension in which the second Gly (Gly(2)) and fourth cysteine (Cys(4)) were
      highly conserved. Mutagenesis experiments demonstrated that Gly(2) was required
      for membrane binding, possibly via myristoylation. Both Gly(2) and Cys(4) were
      needed for movement, the latter seemingly for protein structure and
      palmitoylation. A three-dimensional model was consistent with these predictions
      as well as with earlier evidence showing that a poplar ortholog is reduced by a
      glutaredoxin rather than NADP-thioredoxin reductase. In demonstrating the
      membrane location and intercellular mobility of Trx h9, the present results
      extend the known boundaries of Trx and suggest a role in cell-to-cell
      communication.

PMID- 20133585
TI  - Induction of ectopic Myc target gene JAG2 augments hypoxic growth and
      tumorigenesis in a human B-cell model.
AB  - Ectopic Myc expression plays a key role in human tumorigenesis, and Myc dose
      dependent tumorigenesis has been well established in transgenic mice, but the Myc
      target genes that are dependent on Myc levels have not been well characterized.
      In this regard, we used the human P493-6 B cells, which have a preneoplastic
      state dependent on the Epstein-Barr viral EBNA2 protein and a neoplastic state
      with ectopic inducible Myc, to identify putative ectopic Myc target genes. Among
      the ectopic targets, JAG2 that encodes a Notch receptor ligand Jagged2, was
      directly induced by Myc. Inhibition of Notch signaling through RNAi targeting
      JAG2 or the gamma-secretase Notch inhibitor N-[N-(3,5-difluorophenacetyl)-L
      alanyl]-(S)-phenylglycine t-butyl ester (DAPT) preferentially inhibited the
      neoplastic state in vitro. Furthermore, P493-6 tumorigenesis was inhibited by
      DAPT in vivo. Ectopic expression of JAG2 did not enhance aerobic cell
      proliferation, but increased proliferation of hypoxic cells in vitro and
      significantly increased in vivo tumorigenesis. Furthermore, the expression of
      Jagged2 in P493-6 tumors often overlapped with regions of hypoxia. These
      observations suggest that Notch signaling downstream of Myc enables cells to
      adapt in the tumor hypoxic microenvironment.

PMID- 20133586
TI  - Dynamics of intracellular bacterial replication at the single cell level.
AB  - Several important pathogens cause disease by surviving and replicating within
      host cells. Bacterial proliferation is the product of both replication and
      killing undergone by the population. However, these processes are difficult to
      distinguish, and are usually assessed together by determination of net bacterial
      load. In addition, measurement of net load does not reveal heterogeneity within
      pathogen populations. This is particularly important in persistent infections in
      which slow or nongrowing bacteria are thought to have a major impact. Here we
      report the development of a reporter system based on fluorescence dilution that
      enables direct quantification of the replication dynamics of Salmonella enterica
      serovar Typhimurium (S. Typhimurium) in murine macrophages at both the population
      and single-cell level. We used this technique to demonstrate that a major S.
      Typhimurium virulence determinant, the Salmonella pathogenicity island 2 type III
      secretion system, is required for bacterial replication but does not have a major
      influence on resistance to killing. Furthermore, we found that, upon entry into
      macrophages, many bacteria do not replicate, but appear to enter a dormant-like
      state. These could represent an important reservoir of persistent bacteria. The
      approach could be extended to other pathogens to study the contribution of
      virulence and host resistance factors to replication and killing, and to identify
      and characterize nonreplicating bacteria associated with chronic or latent
      infections.

PMID- 20133587
TI  - Aberrant overexpression and function of the miR-17-92 cluster in MLL-rearranged
      acute leukemia.
AB  - MicroRNA (miRNA)-17-92 cluster (miR-17-92), containing seven individual miRNAs,
      is frequently amplified and overexpressed in lymphomas and various solid tumors.
      We have found that it is also frequently amplified and the miRNAs are aberrantly
      overexpressed in mixed lineage leukemia (MLL)-rearranged acute leukemias.
      Furthermore, we show that MLL fusions exhibit a much stronger direct binding to
      the locus of this miRNA cluster than does wild-type MLL; these changes are
      associated with elevated levels of histone H3 acetylation and H3K4 trimethylation
      and an up-regulation of these miRNAs. We further observe that forced expression
      of this miRNA cluster increases proliferation and inhibits apoptosis of human
      cells. More importantly, we show that this miRNA cluster can significantly
      increase colony-forming capacity of normal mouse bone marrow progenitor cells
      alone and, particularly, in cooperation with MLL fusions. Finally, through
      combinatorial analysis of miRNA and mRNA arrays of mouse bone marrow progenitor
      cells transfected with this miRNA cluster and/or MLL fusion gene, we identified
      363 potential miR-17-92 target genes that exhibited a significant inverse
      correlation of expression with the miRNAs. Remarkably, these potential target
      genes are significantly enriched (P < 0.01; >2-fold) in cell differentiation,
      hematopoiesis, cell cycle, and apoptosis. Taken together, our studies suggest
      that overexpression of miR-17-92 cluster in MLL-rearranged leukemias is likely
      attributed to both DNA copy number amplification and direct up-regulation by MLL
      fusions, and that the miRNAs in this cluster may play an essential role in the
      development of MLL-associated leukemias through inhibiting cell differentiation
      and apoptosis, while promoting cell proliferation, by regulating relevant target
      genes.

PMID- 20133588
TI  - Area-specific temporal control of corticospinal motor neuron differentiation by
      COUP-TFI.
AB  - Transcription factors with gradients of expression in neocortical progenitors
      give rise to distinct motor and sensory cortical areas by controlling the area
      specific differentiation of distinct neuronal subtypes. However, the molecular
      mechanisms underlying this area-restricted control are still unclear. Here, we
      show that COUP-TFI controls the timing of birth and specification of
      corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a
      CSMN differentiation program. Loss of COUP-TFI function causes an area-specific
      premature generation of neurons with cardinal features of CSMN, which project to
      subcerebral structures, including the spinal cord. Concurrently, genuine CSMN
      differentiate imprecisely and do not project beyond the pons, together resulting
      in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of
      function. Our findings indicate that COUP-TFI exerts critical areal and temporal
      control over the precise differentiation of CSMN during corticogenesis, thereby
      enabling the area-specific functional features of motor and sensory areas to
      arise.

PMID- 20133589
TI  - Language acquisition in premature and full-term infants.
AB  - We tested healthy preterm (born near 28 +/- 2 weeks of gestational age) and full
      term infants at various different ages. We compared the two populations on the
      development of a language acquisition landmark, namely, the ability to
      distinguish the native language from a rhythmically similar one. This ability is
      attained 4 months after birth in healthy full-term infants. We measured the
      induced gamma-band power associated with passive listening to (i) the infants'
      native language (Spanish), (ii) a rhythmically close language (Italian), and
      (iii) a rhythmically distant language (Japanese) as a marker of gains in language
      discrimination. Preterm and full-term infants were matched for neural maturation
      and duration of exposure to broadcast speech. We found that both full-term and
      preterm infants only display a response to native speech near 6 months after
      their term age. Neural maturation seems to constrain advances in speech
      discrimination at early stages of language acquisition.

PMID- 20133590
TI  - Cell density and mobility protect swarming bacteria against antibiotics.
AB  - Swarming bacteria move in multicellular groups and exhibit adaptive resistance to
      multiple antibiotics. Analysis of this phenomenon has revealed the protective
      power of high cell densities to withstand exposure to otherwise lethal antibiotic
      concentrations. We find that high densities promote bacterial survival, even in a
      nonswarming state, but that the ability to move, as well as the speed of
      movement, confers an added advantage, making swarming an effective strategy for
      prevailing against antimicrobials. We find no evidence of induced resistance
      pathways or quorum-sensing mechanisms controlling this group resistance, which
      occurs at a cost to cells directly exposed to the antibiotic. This work has
      relevance to the adaptive antibiotic resistance of bacterial biofilms.

PMID- 20133591
TI  - Cancer stem cells from colorectal cancer-derived cell lines.
AB  - Cancer stem cells (CSCs) are the subpopulation of cells within a tumor that can
      self-renew, differentiate into multiple lineages, and drive tumor growth. Here we
      describe a two-pronged approach for the identification and characterization of
      CSCs from colorectal cancer cell lines, using a Matrigel-based differentiation
      assay, and cell surface markers CD44 and CD24. About 20 to 30% of cells from the
      SW1222 cell line form megacolonies in Matrigel that have complex 3D structures
      resembling colonic crypts. The megacolonies' capacity to self-renew in vitro is
      direct evidence that they contain the CSCs. Furthermore, just 200 cells from
      SW1222 megacolonies initiate tumors in NOD/SCID mice. We also showed that
      CD44(+)CD24(+) cells enriched for colorectal CSCs in the HT29 and SW1222 cell
      lines, which can self-renew and reform all four CD44/CD24 subpopulations, are the
      most clonogenic in vitro and can initiate tumors in vivo. A single SW1222
      CD44(+)CD24(+) CSC, when grown in Matrigel, can form large megacolonies that
      differentiate into enterocyte, enteroendocrine, and goblet cell lineages. The
      HCT116 line does not differentiate or express CDX1, nor does it contain
      subpopulations of cells with greater tumor-forming capacity, suggesting that
      HCT116 contains mainly CSCs. However, forced expression of CDX1 in HCT116 leads
      to reduced clonogenicity and production of differentiating crypt-containing
      colonies, which can explain the selection for reduced CDX1 expression in many
      colorectal cancers. In summary, colorectal cancer cell lines contain
      subpopulations of CSCs, characterized by their cell surface markers and colony
      morphology, which can self-renew and differentiate into multiple lineages.

PMID- 20133592
TI  - A fast, single-vesicle fusion assay mimics physiological SNARE requirements.
AB  - Almost all known intracellular fusion reactions are driven by formation of trans
      SNARE complexes through pairing of vesicle-associated v-SNAREs with complementary
      t-SNAREs on target membranes. However, the number of SNARE complexes required for
      fusion is unknown, and there is controversy about whether additional proteins are
      required to explain the fast fusion which can occur in cells. Here we show that
      single vesicles containing the synaptic/exocytic v-SNAREs VAMP/synaptobrevin fuse
      rapidly with planar, supported bilayers containing the synaptic/exocytic t-SNAREs
      syntaxin-SNAP25. Fusion rates decreased dramatically when the number of
      externally oriented v-SNAREs per vesicle was reduced below 5-10, directly
      establishing this as the minimum number required for rapid fusion. Docking-to
      fusion delay time distributions were consistent with a requirement that 5-11 t
      SNAREs be recruited to achieve fusion, closely matching the v-SNARE requirement.

PMID- 20133593
TI  - Proteogenomic basis for ecological divergence of closely related bacteria in
      natural acidophilic microbial communities.
AB  - Bacterial species concepts are controversial. More widely accepted is the need to
      understand how differences in gene content and sequence lead to ecological
      divergence. To address this relationship in ecosystem context, we investigated
      links between genotype and ecology of two genotypic groups of Leptospirillum
      group II bacteria in comprehensively characterized, natural acidophilic biofilm
      communities. These groups share 99.7% 16S rRNA gene sequence identity and 95%
      average amino acid identity between their orthologs. One genotypic group
      predominates during early colonization, and the other group typically
      proliferates in later successional stages, forming distinct patches tens to
      hundreds of micrometers in diameter. Among early colonizing populations, we
      observed dominance of five genotypes that differed from each other by the extent
      of recombination with the late colonizing type. Our analyses suggest that the
      specific recombinant variant within the early colonizing group is selected for by
      environmental parameters such as temperature, consistent with recombination as a
      mechanism for ecological fine tuning. Evolutionary signatures, and strain
      resolved expression patterns measured via mass spectrometry-based proteomics,
      indicate increased cobalamin biosynthesis, (de)methylation, and glycine cleavage
      in the late colonizer. This may suggest environmental changes within the biofilm
      during development, accompanied by redirection of compatible solutes from
      osmoprotectants toward metabolism. Across 27 communities, comparative
      proteogenomic analyses show that differential regulation of shared genes and
      expression of a small subset of the approximately 15% of genes unique to each
      genotype are involved in niche partitioning. In summary, the results show how
      subtle genetic variations can lead to distinct ecological strategies.

PMID- 20133594
TI  - Development of the circadian oscillator during differentiation of mouse embryonic
      stem cells in vitro.
AB  - The molecular oscillations underlying the generation of circadian rhythmicity in
      mammals develop gradually during ontogenesis. However, the developmental process
      of mammalian cellular circadian oscillator formation remains unknown. In
      differentiated somatic cells, the transcriptional-translational feedback loops
      (TTFL) consisting of clock genes elicit the molecular circadian oscillation.
      Using a bioluminescence imaging system to monitor clock gene expression, we show
      here that the circadian bioluminescence rhythm is not detected in the mouse
      embryonic stem (ES) cells, and that the ES cells likely lack TTFL regulation for
      clock gene expression. The circadian clock oscillation was induced during the
      differentiation culture of mouse ES cells without maternal factors. In addition,
      reprogramming of the differentiated cells by expression of Sox2, Klf4, Oct3/4,
      and c-Myc genes, which were factors to generate induced pluripotent stem (iPS)
      cells, resulted in the re-disappearance of circadian oscillation. These results
      demonstrate that an intrinsic program controls the formation of the circadian
      oscillator during the differentiation process of ES cells in vitro. The cellular
      differentiation and reprogramming system using cultured ES cells allows us to
      observe the circadian clock formation process and may help design new strategies
      to understand the key mechanisms responsible for the organization of the
      molecular oscillator in mammals.

PMID- 20133595
TI  - Screening the mammalian extracellular proteome for regulators of embryonic human
      stem cell pluripotency.
AB  - Approximately 3,500 mammalian genes are predicted to be secreted or single-pass
      transmembrane proteins. The function of the majority of these genes is still
      unknown, and a number of the encoded proteins might find use as new therapeutic
      agents themselves or as targets for small molecule or antibody drug development.
      To analyze the physiological activities of the extracellular proteome, we
      developed a large-scale, high-throughput protein expression, purification, and
      screening platform. For this study, the complete human extracellular proteome was
      analyzed and prioritized based on genome-wide disease association studies to
      select 529 initial target genes. These genes were cloned into three expression
      vectors as native sequences and as N-terminal and C-terminal Fc fusions to create
      an initial collection of 806 purified secreted proteins. To determine its
      utility, this library was screened in an OCT4-based cellular assay to identify
      regulators of human embryonic stem-cell self-renewal. We found that the pigment
      epithelium-derived factor can promote long-term pluripotent growth of human
      embryonic stem cells without bFGF or TGFbeta/Activin/Nodal ligand
      supplementation. Our results further indicate that activation of the pigment
      epithelium-derived factor receptor-Erk1/2 signaling pathway by the pigment
      epithelium-derived factor is sufficient to maintain the self-renewal of
      pluripotent human embryonic stem cells. These experiments illustrate the
      potential for discovering novel biological functions by directly screening
      protein diversity in cell-based phenotypic or reporter assays.

PMID- 20133596
TI  - Rapid spread of invasive genes into a threatened native species.
AB  - When introduced or cultivated plants or animals hybridize with their native
      relatives, the spread of invasive genes into native populations might have
      biological, aesthetic, and legal implications. Models suggest that the rate of
      displacement of native by invasive alleles can be rapid and inevitable if they
      are favored by natural selection. We document the spread of a few introduced
      genes 90 km into a threatened native species (the California Tiger Salamander) in
      60 years. Meanwhile, a majority of genetic markers (65 of 68) show little
      evidence of spread beyond the region where introductions occurred. Using computer
      simulations, we found that such a pattern is unlikely to emerge by chance among
      selectively neutral markers. Therefore, our results imply that natural selection
      has favored both the movement and fixation of these exceptional invasive alleles.
      The legal status of introgressed populations (native populations that are
      slightly genetically modified) is unresolved by the US Endangered Species Act.
      Our results illustrate that genetic and ecological factors need to be carefully
      weighed when considering different criteria for protection, because different
      rules could result in dramatically different geographic areas and numbers of
      individuals being protected.

PMID- 20133597
TI  - Brain estrogens rapidly strengthen auditory encoding and guide song preference in
      a songbird.
AB  - Higher cognitive function depends on accurate detection and processing of subtle
      features of sensory stimuli. Such precise computations require neural circuits to
      be modulated over rapid timescales, yet this modulation is poorly understood.
      Brain-derived steroids (neurosteroids) can act as fast signaling molecules in the
      vertebrate central nervous system and could therefore modulate sensory processing
      and guide behavior, but there is no empirical evidence for this possibility. Here
      we report that acute inhibition of estrogen production within a cortical-like
      region involved in complex auditory processing disrupts a songbird's ability to
      behaviorally respond to song stimuli. Identical manipulation of local estrogen
      levels rapidly changes burst firing of single auditory neurons. This acute
      estrogen-mediated modulation targets song and not other auditory stimuli,
      possibly enabling discrimination among species-specific signals. Our results
      demonstrate a crucial role for neuroestrogen synthesis among vertebrates for
      enhanced sensory encoding. Cognitive impairments associated with estrogen
      depletion, including verbal memory loss in humans, may therefore stem from
      compromised moment-by-moment estrogen actions in higher-order cortical circuits.

PMID- 20133598
TI  - NANOS2 interacts with the CCR4-NOT deadenylation complex and leads to suppression
      of specific RNAs.
AB  - Nanos is one of the evolutionarily conserved proteins implicated in germ cell
      development. We have previously shown that NANOS2 plays an important role in both
      the maintenance and sexual development of germ cells. However, the molecular
      mechanisms underlying these events have remained elusive. In our present study,
      we found that NANOS2 localizes to the P-bodies, known centers of RNA degradation
      that are abundantly accumulated in male gonocytes. We further identified by
      immunoprecipitation that the components of the CCR4-NOT deadenylation complex are
      NANOS2-interacting proteins and found that NANOS2 promotes the localization of
      CNOT proteins to P-bodies in vivo. We also elucidated that the NANOS2/CCR4-NOT
      complex has deadenylase activity in vitro, and that some of the RNAs implicated
      in meiosis interact with NANOS2 and are accumulated in its absence. Our current
      data thus indicate that the expression of these RNA molecules is normally
      suppressed via a NANOS2-mediated mechanism. We propose from our current findings
      that NANOS2-interacting RNAs may be recruited to P-bodies and degraded by the
      enzymes contained therein through NANOS2-mediated deadenylation.

PMID- 20133599
TI  - Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission
      and epilepsy.
AB  - Epilepsy is a devastating and poorly understood disease. Mutations in a secreted
      neuronal protein, leucine-rich glioma inactivated 1 (LGI1), were reported in
      patients with an inherited form of human epilepsy, autosomal dominant partial
      epilepsy with auditory features (ADPEAF). Here, we report an essential role of
      LGI1 as an antiepileptogenic ligand. We find that loss of LGI1 in mice (LGI1(-/
      )) causes lethal epilepsy, which is specifically rescued by the neuronal
      expression of LGI1 transgene, but not LGI3. Moreover, heterozygous mice for the
      LGI1 mutation (LGI1(+/-)) show lowered seizure thresholds. Extracellularly
      secreted LGI1 links two epilepsy-related receptors, ADAM22 and ADAM23, in the
      brain and organizes a transsynaptic protein complex that includes presynaptic
      potassium channels and postsynaptic AMPA receptor scaffolds. A lack of LGI1
      disrupts this synaptic protein connection and selectively reduces AMPA receptor
      mediated synaptic transmission in the hippocampus. Thus, LGI1 may serve as a
      major determinant of brain excitation, and the LGI1 gene-targeted mouse provides
      a good model for human epilepsy.

PMID- 20133600
TI  - Cell type specificity of chromatin organization mediated by CTCF and cohesin.
AB  - CTCF sites are abundant in the genomes of diverse species but their function is
      enigmatic. We used chromosome conformation capture to determine long-range
      interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11
      encompassing the beta-globin locus and flanking olfactory receptor genes.
      Although CTCF occupies these sites in both erythroid K562 cells and fibroblast
      293T cells, the long-range interaction frequencies among the sites are highly
      cell type specific, revealing a more densely clustered organization in the
      absence of globin gene activity. Both CTCF and cohesins are required for the cell
      type-specific chromatin conformation. Furthermore, loss of the organizational
      loops in K562 cells through reduction of CTCF with shRNA results in acquisition
      of repressive histone marks in the globin locus and reduces globin gene
      expression whereas silent flanking olfactory receptor genes are unaffected. These
      results support a genome-wide role for CTCF/cohesin sites through loop formation
      that both influences transcription and contributes to cell-type-specific
      chromatin organization and function.

PMID- 20133601
TI  - Positive selection of a duplicated UV-sensitive visual pigment coincides with
      wing pigment evolution in Heliconius butterflies.
AB  - The butterfly Heliconius erato can see from the UV to the red part of the light
      spectrum with color vision proven from 440 to 640 nm. Its eye is known to contain
      three visual pigments, rhodopsins, produced by an 11-cis-3-hydroxyretinal
      chromophore together with long wavelength (LWRh), blue (BRh) and UV (UVRh1)
      opsins. We now find that H. erato has a second UV opsin mRNA (UVRh2)-a previously
      undescribed duplication of this gene among Lepidoptera. To investigate its
      evolutionary origin, we screened eye cDNAs from 14 butterfly species in the
      subfamily Heliconiinae and found both copies only among Heliconius. Phylogeny
      based tests of selection indicate positive selection of UVRh2 following
      duplication, and some of the positively selected sites correspond to vertebrate
      visual pigment spectral tuning residues. Epi-microspectrophotometry reveals two
      UV-absorbing rhodopsins in the H. erato eye with lambda(max) = 355 nm and 398 nm.
      Along with the additional UV opsin, Heliconius have also evolved 3-hydroxy-DL
      kynurenine (3-OHK)-based yellow wing pigments not found in close relatives.
      Visual models of how butterflies perceive wing color variation indicate this has
      resulted in an expansion of the number of distinguishable yellow colors on
      Heliconius wings. Functional diversification of the UV-sensitive visual pigments
      may help explain why the yellow wing pigments of Heliconius are so colorful in
      the UV range compared to the yellow pigments of close relatives lacking the UV
      opsin duplicate.

PMID- 20133602
TI  - Two closely related endocytic proteins that share a common OCRL-binding motif
      with APPL1.
AB  - Mutations of the inositol 5' phosphatase oculocerebrorenal syndrome of Lowe
      (OCRL) give rise to the congenital X-linked disorders oculocerebrorenal syndrome
      of Lowe and Dent disease, two conditions giving rise to abnormal kidney proximal
      tubule reabsorption, and additional nervous system and ocular defects in the case
      of Lowe syndrome. Here, we identify two closely related endocytic proteins, Ses1
      and Ses2, which interact with the ASH-RhoGAP-like (ASPM-SPD-2-Hydin homology and
      Rho-GTPase Activating Domain-like) domain of OCRL. The interaction is mediated by
      a short amino acid motif similar to that used by the rab-5 effector APPL1
      (Adaptor Protein containing pleckstrin homology [PH] domain, PTB domain and
      Leucine zipper motif 1) APPL1 for OCRL binding. Ses binding is mutually exclusive
      with APPL1 binding, and is disrupted by the same missense mutations in the ASH
      RhoGAP-like domain that also disrupt APPL1 binding. Like APPL1, Ses1 and -2 are
      localized on endosomes but reside on different endosomal subpopulations. These
      findings define a consensus motif (which we have called a phenylalanine and
      histidine [F&H] motif) for OCRL binding and are consistent with a scenario in
      which Lowe syndrome and Dent disease result from perturbations at multiple sites
      within the endocytic pathway.

PMID- 20133603
TI  - Evidence for the role of organics in aerosol particle formation under atmospheric
      conditions.
AB  - New particle formation in the atmosphere is an important parameter in governing
      the radiative forcing of atmospheric aerosols. However, detailed nucleation
      mechanisms remain ambiguous, as laboratory data have so far not been successful
      in explaining atmospheric nucleation. We investigated the formation of new
      particles in a smog chamber simulating the photochemical formation of H(2)SO(4)
      and organic condensable species. Nucleation occurs at H(2)SO(4) concentrations
      similar to those found in the ambient atmosphere during nucleation events. The
      measured particle formation rates are proportional to the product of the
      concentrations of H(2)SO(4) and an organic molecule. This suggests that only one
      H(2)SO(4) molecule and one organic molecule are involved in the rate-limiting
      step of the observed nucleation process. Parameterizing this process in a global
      aerosol model results in substantially better agreement with ambient observations
      compared to control runs.

PMID- 20133604
TI  - Engineered vascularized bone grafts.
AB  - Clinical protocols utilize bone marrow to seed synthetic and decellularized
      allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow
      derived cytokines induce host neovascularization at the graft surface, but
      hypoxic conditions cause cell death at the core. Addition of cellular components
      that generate an extensive primitive plexus-like vascular network that would
      perfuse the entire scaffold upon anastomosis could potentially yield
      significantly higher-quality grafts. We used a mouse model to develop a two-stage
      protocol for generating vascularized bone grafts using mesenchymal stem cells
      (hMSCs) from human bone marrow and umbilical cord-derived endothelial cells. The
      endothelial cells formed tube-like structures and subsequently networks
      throughout the bone scaffold 4-7 days after implantation. hMSCs were essential
      for stable vasculature both in vitro and in vivo; however, contrary to
      expectations, vasculature derived from hMSCs briefly cultured in medium designed
      to maintain a proliferative, nondifferentiated state was more extensive and
      stable than that with hMSCs with a TGF-beta-induced smooth muscle cell phenotype.
      Anastomosis occurred by day 11, with most hMSCs associating closely with the
      network. Although initially immature and highly permeable, at 4 weeks the network
      was mature. Initiation of scaffold mineralization had also occurred by this
      period. Some human-derived vessels were still present at 5 months, but the
      majority of the graft vasculature had been functionally remodeled with host
      cells. In conclusion, clinically relevant progenitor sources for pericytes and
      endothelial cells can serve to generate highly functional microvascular networks
      for tissue engineered bone grafts.

PMID- 20133605
TI  - Lipid signaling in cytosolic phospholipase A2alpha-cyclooxygenase-2 cascade
      mediates cerebellar long-term depression and motor learning.
AB  - In this study, we show the crucial roles of lipid signaling in long-term
      depression (LTD), that is, synaptic plasticity prevailing in cerebellar Purkinje
      cells. In mouse brain slices, we found that cPLA(2)alpha knockout blocked LTD
      induction, which was rescued by replenishing arachidonic acid (AA) or
      prostaglandin (PG) D(2) or E(2). Moreover, cyclooxygenase (COX)-2 inhibitors
      block LTD, which is rescued by supplementing PGD(2)/E(2). The blockade or rescue
      occurs when these reagents are applied within a time window of 5-15 min following
      the onset of LTD-inducing stimulation. Furthermore, PGD(2)/E(2) facilitates the
      chemical induction of LTD by a PKC activator but is unable to rescue the LTD
      blocked by a PKC inhibitor. We conclude that PGD(2)/E(2) mediates LTD jointly
      with PKC, and suggest possible pathways for their interaction. Finally, we
      demonstrate in awake mice that cPLA(2)alpha deficiency or COX-2 inhibition
      attenuates short-term adaptation of optokinetic eye movements, supporting the
      view that LTD underlies motor learning.

PMID- 20133606
TI  - A broad-spectrum antiviral targeting entry of enveloped viruses.
AB  - We describe an antiviral small molecule, LJ001, effective against numerous
      enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses,
      bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the
      compound had no effect on the infection of nonenveloped viruses. In vitro and in
      vivo assays showed no overt toxicity. LJ001 specifically intercalated into viral
      membranes, irreversibly inactivated virions while leaving functionally intact
      envelope proteins, and inhibited viral entry at a step after virus binding but
      before virus-cell fusion. LJ001 pretreatment also prevented virus-induced
      mortality from Ebola and Rift Valley fever viruses. Structure-activity
      relationship analyses of LJ001, a rhodanine derivative, implicated both the polar
      and nonpolar ends of LJ001 in its antiviral activity. LJ001 specifically
      inhibited virus-cell but not cell-cell fusion, and further studies with lipid
      biosynthesis inhibitors indicated that LJ001 exploits the therapeutic window that
      exists between static viral membranes and biogenic cellular membranes with
      reparative capacity. In sum, our data reveal a class of broad-spectrum antivirals
      effective against enveloped viruses that target the viral lipid membrane and
      compromises its ability to mediate virus-cell fusion.

PMID- 20133607
TI  - Analysis of CD161 expression on human CD8+ T cells defines a distinct functional
      subset with tissue-homing properties.
AB  - CD8(+) T lymphocytes play a key role in host defense, in particular against
      important persistent viruses, although the critical functional properties of such
      cells in tissue are not fully defined. We have previously observed that CD8(+) T
      cells specific for tissue-localized viruses such as hepatitis C virus express
      high levels of the C-type lectin CD161. To explore the significance of this, we
      examined CD8(+)CD161(+) T cells in healthy donors and those with hepatitis C
      virus and defined a population of CD8(+) T cells with distinct homing and
      functional properties. These cells express high levels of CD161 and a pattern of
      molecules consistent with type 17 differentiation, including cytokines (e.g., IL
      17, IL-22), transcription factors (e.g., retinoic acid-related orphan receptor
      gamma-t, P = 6 x 10(-9); RUNX2, P = 0.004), cytokine receptors (e.g., IL-23R, P =
      2 x 10(-7); IL-18 receptor, P = 4 x 10(-6)), and chemokine receptors (e.g., CCR6,
      P = 3 x 10(-8); CXCR6, P = 3 x 10(-7); CCR2, P = 4 x 10(-7)). CD161(+)CD8(+) T
      cells were markedly enriched in tissue samples and coexpressed IL-17 with high
      levels of IFN-gamma and/or IL-22. The levels of polyfunctional cells in tissue
      was most marked in those with mild disease (P = 0.0006). These data define a T
      cell lineage that is present already in cord blood and represents as many as one
      in six circulating CD8(+) T cells in normal humans and a substantial fraction of
      tissue-infiltrating CD8(+) T cells in chronic inflammation. Such cells play a
      role in the pathogenesis of chronic hepatitis and arthritis and potentially in
      other infectious and inflammatory diseases of man.

PMID- 20133608
TI  - Bacterial translation elongation factor EF-Tu interacts and colocalizes with
      actin-like MreB protein.
AB  - We show that translation initiation factor EF-Tu plays a second important role in
      cell shape maintenance in the bacterium Bacillus subtilis. EF-Tu localizes in a
      helical pattern underneath the cell membrane and colocalizes with MreB, an actin
      like cytoskeletal element setting up rod cell shape. The localization of MreB and
      of EF-Tu is interdependent, but in contrast to the dynamic MreB filaments, EF-Tu
      structures are more static and may serve as tracks for MreB filaments. In
      agreement with this idea, EF-Tu and MreB interact in vivo and in vitro. Lowering
      of the EF-Tu levels had a minor effect on translation but a strong effect on cell
      shape and on the localization of MreB, and blocking of the function of EF-Tu in
      translation did not interfere with the localization of MreB, showing that,
      directly or indirectly, EF-Tu affects the cytoskeletal MreB structure and thus
      serves two important functions in a bacterium.

PMID- 20133609
TI  - Premature replacement of mu with alpha immunoglobulin chains impairs
      lymphopoiesis and mucosal homing but promotes plasma cell maturation.
AB  - Sequentially along B cell differentiation, the different classes of membrane Ig
      heavy chains associate with the Ig alpha/Ig beta heterodimer within the B cell
      receptor (BCR). Whether each Ig class conveys specific signals adapted to the
      corresponding differentiation stage remains debated. We investigated the impact
      of the forced expression of an IgA-class receptor throughout murine B cell
      differentiation by knocking in the human C alpha Ig gene in place of the S mu
      region. Despite expression of a functional BCR, homozygous mutant mice showed a
      partial developmental blockade at the pro-B/pre-BI and large pre-BII cell stages,
      with decreased numbers of small pre-BII cells. Beyond this stage, peripheral B
      cell compartments of reduced size developed and allowed specific antibody
      responses, whereas mature cells showed constitutive activation and a strong
      commitment to plasma cell differentiation. Secreted IgA correctly assembled into
      polymers, associated with the murine J chain, and was transported into
      secretions. In heterozygous mutants, cells expressing the IgA allele competed
      poorly with those expressing IgM from the wild-type allele and were almost
      undetectable among peripheral B lymphocytes, notably in gut-associated lymphoid
      tissues. Our data indicate that the IgM BCR is more efficient in driving early B
      cell education and in mucosal site targeting, whereas the IgA BCR appears
      particularly suited to promoting activation and differentiation of effector
      plasma cells.

PMID- 20133610
TI  - Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function.
AB  - In Drosophila, Pumilio (Pum) is important for neuronal homeostasis as well as
      learning and memory. We have recently characterized a mammalian homolog of Pum,
      Pum2, which is found in discrete RNA-containing particles in the somatodendritic
      compartment of polarized neurons. In this study, we investigated the role of Pum2
      in developing and mature neurons by RNA interference. In immature neurons, loss
      of Pum2 led to enhanced dendritic outgrowth and arborization. In mature neurons,
      Pum2 down-regulation resulted in a significant reduction in dendritic spines and
      an increase in elongated dendritic filopodia. Furthermore, we observed an
      increase in excitatory synapse markers along dendritic shafts.
      Electrophysiological analysis of synaptic function of neurons lacking Pum2
      revealed an increased miniature excitatory postsynaptic current frequency. We
      then identified two specific mRNAs coding for a known translational regulator,
      eIF4E, and for a voltage-gated sodium channel, Scn1a, which interacts with Pum2
      in immunoprecipitations from brain lysates. Finally, we show that Pum2 regulates
      translation of the eIF4E mRNA. Taken together, our data reveal a previously
      undescribed role for Pum2 in dendrite morphogenesis, synapse function, and
      translational control.

PMID- 20133611
TI  - STAT5-glucocorticoid receptor interaction and MTF-1 regulate the expression of
      ZnT2 (Slc30a2) in pancreatic acinar cells.
AB  - The exocrine pancreas plays an important role in endogenous zinc loss by
      regulating excretion into the intestinal tract and hence influences the dietary
      zinc requirement. The present experiments show that the zinc transporter ZnT2
      (Slc30a2) is localized to the zymogen granules and that dietary zinc restriction
      in mice decreased the zinc concentration of zymogen granules and ZnT2 expression.
      Excess zinc given orally increased ZnT2 expression and was associated with
      increased pancreatic zinc accumulation. Rat AR42J acinar cells when induced into
      a secretory phenotype, using the glucocorticoid analog dexamethasone (DEX),
      exhibited increased ZnT2 expression and labile zinc as measured with a
      fluorophore. DEX administrated to mice also induced ZnT2 expression that
      accompanied a reduction of the pancreatic zinc content. ZnT2 promoter analyses
      identified elements required for responsiveness to zinc and DEX. Zinc regulation
      was traced to a MRE located downstream from the ZnT2 transcription start site.
      Responsiveness to DEX is produced by two upstream STAT5 binding sites that
      require the glucocorticoid receptor for activation. ZnT2 knockdown in the AR42J
      cells using siRNA resulted in increased cytoplasmic zinc and decreased zymogen
      granule zinc that further demonstrated that ZnT2 may mediate the sequestration of
      zinc into zymogen granules. We conclude, based upon experiments with intact mice
      and pancreatic acinar cells in culture, that ZnT2 participates in zinc transport
      into pancreatic zymogen granules through a glucocorticoid pathway requiring
      glucocorticoid receptor and STAT5, and zinc-regulated signaling pathways
      requiring MTF-1. The ZnT2 transporter appears to function in a physiologically
      responsive manner involving entero-pancreatic zinc trafficking.

PMID- 20133612
TI  - Induced allostery in the directed evolution of an enantioselective Baeyer
      Villiger monooxygenase.
AB  - The molecular basis of allosteric effects, known to be caused by an effector
      docking to an enzyme at a site distal from the binding pocket, has been studied
      recently by applying directed evolution. Here, we utilize laboratory evolution in
      a different way, namely to induce allostery by introducing appropriate distal
      mutations that cause domain movements with concomitant reshaping of the binding
      pocket in the absence of an effector. To test this concept, the thermostable
      Baeyer-Villiger monooxygenase, phenylacetone monooxygenase (PAMO), was chosen as
      the enzyme to be employed in asymmetric Baeyer-Villiger reactions of substrates
      that are not accepted by the wild type. By using the known X-ray structure of
      PAMO, a decision was made regarding an appropriate site at which saturation
      mutagenesis is most likely to generate mutants capable of inducing allostery
      without any effector compound being present. After screening only 400
      transformants, a double mutant was discovered that catalyzes the asymmetric
      oxidative kinetic resolution of a set of structurally different 2-substituted
      cyclohexanone derivatives as well as the desymmetrization of three different 4
      substituted cyclohexanones, all with high enantioselectivity. Molecular dynamics
      (MD) simulations and covariance maps unveiled the origin of increased substrate
      scope as being due to allostery. Large domain movements occur that expose and
      reshape the binding pocket. This type of focused library production, aimed at
      inducing significant allosteric effects, is a viable alternative to traditional
      approaches to "designed" directed evolution that address the binding site
      directly.

PMID- 20133613
TI  - An efficient, multiply promiscuous hydrolase in the alkaline phosphatase
      superfamily.
AB  - We report a catalytically promiscuous enzyme able to efficiently promote the
      hydrolysis of six different substrate classes. Originally assigned as a
      phosphonate monoester hydrolase (PMH) this enzyme exhibits substantial second
      order rate accelerations ((k(cat)/K(M))/k(w)), ranging from 10(7) to as high as
      10(19), for the hydrolyses of phosphate mono-, di-, and triesters, phosphonate
      monoesters, sulfate monoesters, and sulfonate monoesters. This substrate
      collection encompasses a range of substrate charges between 0 and -2, transition
      states of a different nature, and involves attack at two different reaction
      centers (P and S). Intrinsic reactivities (half-lives) range from 200 days to
      10(5) years under near neutrality. The substantial rate accelerations for a set
      of relatively difficult reactions suggest that efficient catalysis is not
      necessarily limited to efficient stabilization of just one transition state. The
      crystal structure of PMH identifies it as a member of the alkaline phosphatase
      superfamily. PMH encompasses four of the native activities previously observed in
      this superfamily and extends its repertoire by two further activities, one of
      which, sulfonate monoesterase, has not been observed previously for a natural
      enzyme. PMH is thus one of the most promiscuous hydrolases described to date. The
      functional links between superfamily activities can be presumed to have played a
      role in functional evolution by gene duplication.

PMID- 20133614
TI  - Ancient mitochondrial DNA analysis reveals complexity of indigenous North
      American turkey domestication.
AB  - Although the cultural and nutritive importance of the turkey (Meleagris
      gallopavo) to precontact Native Americans and contemporary people worldwide is
      clear, little is known about the domestication of this bird compared to other
      domesticates. Mitochondrial DNA analysis of 149 turkey bones and 29 coprolites
      from 38 archaeological sites (200 BC-AD 1800) reveals a unique domesticated breed
      in the precontact Southwestern United States. Phylogeographic analyses indicate
      that this domestic breed originated from outside the region, but rules out the
      South Mexican domestic turkey (Meleagris gallopavo gallopavo) as a progenitor. A
      strong genetic bottleneck within the Southwest turkeys also reflects intensive
      human selection and breeding. This study points to at least two occurrences of
      turkey domestication in precontact North America and illuminates the intensity
      and sophistication of New World animal breeding practices.

PMID- 20133615
TI  - Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and
      represents a model for human LIG4 syndrome.
AB  - DNA ligase IV (LIG4) is an essential component of the nonhomologous end-joining
      (NHEJ) repair pathway and plays a key role in V(D)J recombination. Hypomorphic
      LIG4 mutations in humans are associated with increased cellular radiosensitivity,
      microcephaly, facial dysmorphisms, growth retardation, developmental delay, and a
      variable degree of immunodeficiency. We have generated a knock-in mouse model
      with a homozygous Lig4 R278H mutation that corresponds to the first LIG4 mutation
      reported in humans. The phenotype of homozygous mutant mice Lig4(R278H/R278H)
      (Lig4(R/R)) includes growth retardation, a decreased life span, a severe cellular
      sensitivity to ionizing radiation, and a very severe, but incomplete block in T
      and B cell development. Peripheral T lymphocytes show an activated and anergic
      phenotype, reduced viability, and a restricted repertoire, reminiscent of human
      leaky SCID. Genomic instability is associated with a high rate of thymic tumor
      development. Finally, Lig4(R/R) mice spontaneously produce low-affinity
      antibodies that include autoreactive specificities, but are unable to mount high
      affinity antibody responses. These findings highlight the importance of LIG4 in
      lymphocyte development and function, and in genomic stability maintenance, and
      provide a model for the complex phenotype of LIG4 syndrome in humans.

PMID- 20133616
TI  - Determining the distribution of probes between different subcellular locations
      through automated unmixing of subcellular patterns.
AB  - Many proteins or other biological macromolecules are localized to more than one
      subcellular structure. The fraction of a protein in different cellular
      compartments is often measured by colocalization with organelle-specific
      fluorescent markers, requiring availability of fluorescent probes for each
      compartment and acquisition of images for each in conjunction with the
      macromolecule of interest. Alternatively, tailored algorithms allow finding
      particular regions in images and quantifying the amount of fluorescence they
      contain. Unfortunately, this approach requires extensive hand-tuning of
      algorithms and is often cell type-dependent. Here we describe a machine-learning
      approach for estimating the amount of fluorescent signal in different subcellular
      compartments without hand tuning, requiring only the acquisition of separate
      training images of markers for each compartment. In testing on images of cells
      stained with mixtures of probes for different organelles, we achieved a 93%
      correlation between estimated and expected amounts of probes in each compartment.
      We also demonstrated that the method can be used to quantify drug-dependent
      protein translocations. The method enables automated and unbiased determination
      of the distributions of protein across cellular compartments, and will
      significantly improve imaging-based high-throughput assays and facilitate
      proteome-scale localization efforts.

PMID- 20133617
TI  - Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and
      lymphomagenesis.
AB  - The mechanisms by which microRNA dysfunction contributes to the pathogenesis of
      diffuse large B cell lymphoma (DLBCL) are not well established. The
      identification of the genes and pathways directly targeted by these small
      regulatory RNAs is a critical step to advance this field. Using unbiased genome
      wide approaches in DLBCL, we discovered that the oncogenic microRNA-155 (miR-155)
      directly targets the bone morphogenetic protein (BMP)-responsive transcriptional
      factor SMAD5. Surprisingly, we found that in DLBCL a noncanonical signaling
      module linking TGF-beta1 signals to SMAD5 is also active. In agreement with these
      data, miR-155 overexpression rendered DLBCLs resistant to the growth-inhibitory
      effects of both TGF-beta1 and BMPs, via defective induction of p21 and impaired
      cell cycle arrest. In confirmatory experiments, RNAi-based SMAD5 knockdown
      recapitulated in vitro and in vivo the effects miR-155 overexpression.
      Furthermore, in primary DLBCLs, miR-155 overexpression inhibited SMAD5 expression
      and disrupted its activity, as defined by individual and global analyses of its
      transcriptional targets. Together, our data helped explain miR-155 function,
      highlighted a hitherto unappreciated role of SMAD5 in lymphoma biology, and
      defined a unique mechanism used by cancer cells to escape TGF-beta's growth
      inhibitory effects.

PMID- 20133618
TI  - Three major output pathways from the KaiABC-based oscillator cooperate to
      generate robust circadian kaiBC expression in cyanobacteria.
AB  - Circadian kaiBC expression in the cyanobacterium Synechococcus elongatus PCC 7942
      is generated by temporal information transmission from the KaiABC-based circadian
      oscillator to RpaA, a putative transcriptional factor, via the SasA-dependent
      positive pathway and the LabA-dependent negative pathway which is responsible for
      feedback regulation of KaiC. However, the labA/sasA double mutant has a circadian
      kaiBC expression rhythm, suggesting that there is an additional circadian output
      pathway. Here we describe a third circadian output pathway, which is CikA
      dependent. The cikA mutation attenuates KaiC overexpression-induced kaiBC
      repression and exacerbates the low-amplitude phenotype of the labA mutant,
      suggesting that cikA acts as a negative regulator of kaiBC expression independent
      of the LabA-dependent pathway. In the labA/sasA/cikA triple mutant, kaiBC
      promoter activity becomes almost arrhythmic, despite preservation of the
      circadian KaiC phosphorylation rhythm, suggesting that CikA largely accounts for
      the residual kaiBC expression rhythm observed in the labA/sasA double mutant.
      These results also strongly suggest that transcriptional regulation in the
      labA/sasA/cikA triple mutant is insulated from the circadian signals of the
      KaiABC-based oscillator. Based on these observations, we propose a model in which
      temporal information from the KaiABC-based circadian oscillator is transmitted to
      gene expression through three separate output pathways.

PMID- 20133619
TI  - Ambient temperature response establishes ELF3 as a required component of the core
      Arabidopsis circadian clock.
AB  - Circadian clocks synchronize internal processes with environmental cycles to
      ensure optimal timing of biological events on daily and seasonal time scales.
      External light and temperature cues set the core molecular oscillator to local
      conditions. In Arabidopsis, EARLY FLOWERING 3 (ELF3) is thought to act as an
      evening-specific repressor of light signals to the clock, thus serving a
      zeitnehmer function. Circadian rhythms were examined in completely dark-grown, or
      etiolated, null elf3-1 seedlings, with the clock entrained by thermocycles, to
      evaluate whether the elf3 mutant phenotype was light-dependent. Circadian rhythms
      were absent from etiolated elf3-1 seedlings after exposure to temperature cycles,
      and this mutant failed to exhibit classic indicators of entrainment by
      temperature cues, consistent with global clock dysfunction or strong perturbation
      of temperature signaling in this background. Warm temperature pulses failed to
      elicit acute induction of temperature-responsive genes in elf3-1. In fact, warm
      temperature-responsive genes remained in a constitutively "ON" state because of
      clock dysfunction and, therefore, were insensitive to temperature signals in the
      normal time of day-specific manner. These results show ELF3 is broadly required
      for circadian clock function regardless of light conditions, where ELF3 activity
      is needed by the core oscillator to allow progression from day to night during
      either light or temperature entrainment. Furthermore, robust circadian rhythms
      appear to be a prerequisite for etiolated seedlings to respond correctly to
      temperature signals.

PMID- 20133620
TI  - Blimp1-mediated repression of negative regulators is required for osteoclast
      differentiation.
AB  - Regulation of irreversible cell lineage commitment depends on a delicate balance
      between positive and negative regulators, which comprise a sophisticated network
      of transcription factors. Receptor activator of NF-kappaB ligand (RANKL)
      stimulates the differentiation of bone-resorbing osteoclasts through the
      induction of nuclear factor of activated T cells c1 (NFATc1), the essential
      transcription factor for osteoclastogenesis. Osteoclast-specific robust induction
      of NFATc1 is achieved through an autoamplification mechanism, in which NFATc1 is
      constantly activated by calcium signaling while the negative regulators of NFATc1
      are suppressed. However, it has been unclear how such negative regulators are
      repressed during osteoclastogenesis. Here we show that B lymphocyte-induced
      maturation protein-1 (Blimp1; encoded by Prdm1), which is induced by RANKL
      through NFATc1 during osteoclastogenesis, functions as a transcriptional
      repressor of anti-osteoclastogenic genes such as Irf8 and Mafb. Overexpression of
      Blimp1 leads to an increase in osteoclast formation, and Prdm1-deficient
      osteoclast precursor cells do not undergo osteoclast differentiation efficiently.
      The importance of Blimp1 in bone homeostasis is underscored by the observation
      that mice with an osteoclast-specific deficiency in the Prdm1 gene exhibit a high
      bone mass phenotype caused by a decreased number of osteoclasts. Thus, NFATc1
      choreographs the determination of cell fate in the osteoclast lineage by inducing
      the repression of negative regulators as well as through its effect on positive
      regulators.

PMID- 20133621
TI  - Two distinct mechanisms underlie progesterone-induced proliferation in the
      mammary gland.
AB  - The mouse mammary gland develops postnatally under the control of female
      reproductive hormones. Estrogens and progesterone trigger morphogenesis by poorly
      understood mechanisms acting on a subset of mammary epithelial cells (MECs) that
      express their cognate receptors, estrogen receptor alpha (ERalpha) and
      progesterone receptor (PR). Here, we show that in the adult female, progesterone
      drives proliferation of MECs in two waves. The first, small wave, encompasses
      PR(+) cells and requires cyclin D1, the second, large wave, comprises mostly PR(
      ) cells and relies on the tumor necrosis factor (TNF) family member, receptor
      activator of NF-kappaB-ligand (RANKL). RANKL elicits proliferation by a paracrine
      mechanism. Ablation of RANKL in the mammary epithelium blocks progesterone
      induced morphogenesis, and ectopic expression of RANKL in MECs completely rescues
      the PR(-/-) phenotype. Systemic administration of RANKL triggers proliferation in
      the absence of PR signaling, and injection of a RANK signaling inhibitor
      interferes with progesterone-induced proliferation. Thus, progesterone elicits
      proliferation by a cell-intrinsic and a, more important, paracrine mechanism.

PMID- 20133622
TI  - Recessive mutations in the INS gene result in neonatal diabetes through reduced
      insulin biosynthesis.
AB  - Heterozygous coding mutations in the INS gene that encodes preproinsulin were
      recently shown to be an important cause of permanent neonatal diabetes. These
      dominantly acting mutations prevent normal folding of proinsulin, which leads to
      beta-cell death through endoplasmic reticulum stress and apoptosis. We now report
      10 different recessive INS mutations in 15 probands with neonatal diabetes.
      Functional studies showed that recessive mutations resulted in diabetes because
      of decreased insulin biosynthesis through distinct mechanisms, including gene
      deletion, lack of the translation initiation signal, and altered mRNA stability
      because of the disruption of a polyadenylation signal. A subset of recessive
      mutations caused abnormal INS transcription, including the deletion of the C1 and
      E1 cis regulatory elements, or three different single base-pair substitutions in
      a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an
      earlier and more severe beta-cell defect, patients with recessive INS mutations
      had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed
      earlier (median 1 week vs. 10 weeks) compared to those with dominant INS
      mutations. Mutations in the insulin gene can therefore result in neonatal
      diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the
      recessively inherited mutations provide a genetic demonstration of the essential
      role of multiple sequence elements that regulate the biosynthesis of insulin in
      man.

PMID- 20133623
TI  - An organellar maturase associates with multiple group II introns.
AB  - Bacterial group II introns encode maturase proteins required for splicing. In
      organelles of photosynthetic land plants, most of the group II introns have lost
      the reading frames for maturases. Here, we show that the plastidial maturase MatK
      not only interacts with its encoding intron within trnK-UUU, but also with six
      additional group II introns, all belonging to intron subclass IIA. Mapping
      analyses of RNA binding sites revealed MatK to recognize multiple regions within
      the trnK intron. Organellar group II introns are considered to be the ancestors
      of nuclear spliceosomal introns. That MatK associates with multiple intron
      ligands makes it an attractive model for an early trans-acting nuclear splicing
      activity.

PMID- 20133624
TI  - Activation state and intracellular trafficking contribute to the repertoire of
      endogenous glycosphingolipids presented by CD1d [corrected].
AB  - Myeloid antigen-presenting cells (APC) express CD1d molecules that present
      exogenous and endogenous lipid antigens that activate CD1d-restricted T cells,
      natural killer T (NKT) cells. NKT cell activation has been shown to mediate the
      potent downstream activation of other immune cells through cell-cell interactions
      and rapid, prolific cytokine production. Foreign antigens are not required for
      NKT cell activation. The endogenous lipids bound to CD1d are sufficient for
      activation of NKT cells in the setting of Toll-like receptor-induced cytokines.
      The most potent NKT cell antigens identified are glycosphingolipids (GSL). The
      GSL repertoire of endogenous ligands bound to CD1d molecules that are expressed
      in myeloid APC at steady state and in the setting of activation has not been
      delineated. This report identifies the range of GSL bound to soluble murine CD1d
      (mCD1d) molecules that sample the endoplasmic reticulum/secretory routes and cell
      surface-cleaved mCD1d that also samples the endocytic system. Specific GSL
      species are preferentially bound by mCD1d and do not solely reflect cellular GSL.
      GM1a and GD1a are prominent CD1d ligands for molecules following both the
      ER/secretory and lysosomal trafficking routes, whereas GM2 was eluted from
      soluble CD1d but not lysosomal trafficking CD1d. Further, after LPS activation,
      the quantities of soluble CD1d-bound GM3 and GM1a markedly increased. A unique
      alpha-galactose-terminating GSL was also found to be preferentially bound to
      mCD1d at steady state, and it increased with APC activation. Together, these
      studies identify the range of GSL presented by CD1d and how presentation varies
      based on CD1d intracellular trafficking and microbial activation.

PMID- 20133625
TI  - Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic
      vascular remodeling.
AB  - HYPB is a human histone H3 lysine 36 (H3K36)-specific methyltransferase and acts
      as the ortholog of yeast Set2. This study explored the physiological function of
      mammalian HYPB using knockout mice. Homozygous disruption of Hypb impaired H3K36
      trimethylation but not mono- or dimethylation, and resulted in embryonic
      lethality at E10.5-E11.5. Severe vascular defects were observed in the Hypb(-/-)
      embryo, yolk sac, and placenta. The abnormally dilated capillaries in mutant
      embryos and yolk sacs could not be remodeled into large blood vessels or
      intricate networks, and the aberrantly rounded mesodermal cells exhibited
      weakened interaction with endothelial cells. The embryonic vessels failed to
      invade the labyrinthine layer of placenta, which impaired the embryonic-maternal
      vascular connection. These defects could not be rescued by wild-type tetraploid
      blastocysts, excluding the possibility that they were caused by the
      extraembryonic tissues. Consistent with these phenotypes, gene expression
      profiling in wild-type and Hypb(-/-) yolk sacs revealed that the Hypb disruption
      altered the expression of some genes involved in vascular remodeling. At the
      cellular level, Hypb(-/-) embryonic stem cell-derived embryonic bodies, as well
      as in vitro-cultured human endothelial cells with siRNA-mediated suppression of
      HYPB, showed obvious defects in cell migration and invasion during vessel
      formation, suggesting an intrinsic role of Hypb in vascular development. Taken
      together, these results indicate that Hypb is required for embryonic vascular
      remodeling and provide a tool to study the function of H3K36 methylation in
      vasculogenesis/angiogenesis.

PMID- 20133626
TI  - A mutation of Ikbkg causes immune deficiency without impairing degradation of
      IkappaB alpha.
AB  - Null alleles of the gene encoding NEMO (NF-kappaB essential modulator) are lethal
      in hemizygous mice and men, whereas hypomorphic alleles typically cause a
      syndrome of immune deficiency and ectodermal dysplasia. Here we describe an
      allele of Ikbkg in mice that impaired Toll-like receptor signaling, lymph node
      formation, development of memory and regulatory T cells, and Ig production, but
      did not cause ectodermal dysplasia. Degradation of IkappaB alpha, which is
      considered a primary requirement for NEMO-mediated immune signaling, occurred
      normally in response to Toll-like receptor stimulation, yet ERK phosphorylation
      and NF-kappaB p65 nuclear translocation were severely impaired. This selective
      loss of function highlights the immunological importance of NEMO-regulated
      pathways beyond IkappaB alpha degradation, and offers a biochemical explanation
      for rare immune deficiencies in man.

PMID- 20133627
TI  - Importance of antibody and complement for oxidative burst and killing of invasive
      nontyphoidal Salmonella by blood cells in Africans.
AB  - Bacteremia caused by nontyphoidal strains of Salmonella is endemic among African
      children. Case-fatality rates are high and antibiotic resistance increasing, but
      no vaccine is currently available. T cells are important for clearance of
      Salmonella infection within macrophages, but in Africa, invasive Salmonella
      disease usually manifests in the blood and affects children between 4 months and
      2 y of age, when anti-Salmonella antibody is absent. We have previously found a
      role for complement-fixing bactericidal antibody in protecting these children.
      Here we show that opsonic activity of antibody and complement is required for
      oxidative burst and killing of Salmonella by blood cells in Africans. Induction
      of neutrophil oxidative burst correlated with anti-Salmonella IgG and IgM titers
      and C3 deposition on bacteria and was significantly lower in African children
      younger than 2 y compared with older children. Preopsonizing Salmonella with
      immune serum overcame this deficit, indicating a requirement for antibody and/or
      complement. Using different opsonization procedures, both antibody and complement
      were found to be necessary for optimal oxidative burst, phagocytosis and killing
      of nontyphoidal Salmonella by peripheral blood cells in Africans. Although most
      strains of African nontyphoidal Salmonella can be killed with antibody and
      complement alone, phagocytes in the presence of specific antibody and complement
      can kill strains resistant to killing by immune serum. These findings increase
      the likelihood that an antibody-inducing vaccine will protect against invasive
      nontyphoidal Salmonella disease in African children.

PMID- 20133628
TI  - Evidence for widespread adaptive evolution of gene expression in budding yeast.
AB  - Changes in gene expression have been proposed to underlie many, or even most,
      adaptive differences between species. Despite the increasing acceptance of this
      view, only a handful of cases of adaptive gene expression evolution have been
      demonstrated. To address this discrepancy, we introduce a simple test for lineage
      specific selection on gene expression. Applying the test to genome-wide gene
      expression data from the budding yeast Saccharomyces cerevisiae, we find that
      hundreds of gene expression levels have been subject to lineage-specific
      selection. Comparing these findings with independent population genetic evidence
      of selective sweeps suggests that this lineage-specific selection has resulted in
      recent sweeps at over a hundred genes, most of which led to increased transcript
      levels. Examination of the implicated genes revealed a specific biochemical
      pathway--ergosterol biosynthesis--where the expression of multiple genes has been
      subject to selection for reduced levels. In sum, these results suggest that
      adaptive evolution of gene expression is common in yeast, that regulatory
      adaptation can occur at the level of entire pathways, and that similar genome
      wide scans may be possible in other species, including humans.

PMID- 20133629
TI  - Catching a protein in the act.

PMID- 20133630
TI  - Disruption of the Lcn2 gene in mice suppresses primary mammary tumor formation
      but does not decrease lung metastasis.
AB  - Based largely on studies in xenograft models, lipocalin-2 (Lcn2) has been
      implicated in the progression of multiple types of human tumors, including breast
      cancer. Here we examine the role of Lcn2 in mammary tumorigenesis and lung
      metastasis using an in vivo molecular genetics approach. We crossed a well
      characterized transgenic mouse model of breast cancer, the MMTV-PyMT (mouse
      mammary tumor virus-polyoma middle T antigen) mouse, with two independent gene
      targeted Lcn2(-/-) mouse strains of the 129/Ola or C57BL/6 genetic background.
      The onset and progression of mammary tumor development and lung metastasis in the
      female progeny of these crosses were monitored over a 20-week period. Female
      Lcn2(-/-)MMTV-PyMT mice of the 129/Ola background (Lcn2(-/-)PyMT(129)) showed
      delayed onset of mammary tumors, and both Lcn2(-/-)PyMT(129) mice and Lcn2(-/
      )MMTV-PyMT mice of the C57BL/6 background (Lcn2(-/-)PyMT(B6)) exhibited
      significant decreases in multiplicity and tumor burden (approximately 2- to 3
      fold), as measured by total tumor weight and volume. At the molecular level,
      mammary tumors derived from Lcn2(-/-)PyMT(B6) females showed reduced matrix
      metalloproteinase-9 (MMP-9) activity and a lack of high molecular weight MMP
      activity. However, although increased MMP-9 activity has been linked to tumor
      progression, neither Lcn2(-/-)PyMT(B6) nor Lcn2(-/-)PyMT(129) female mice showed
      a reduction in lung metastases compared to Lcn2(+/+)PyMT controls. Our results
      demonstrate, using an in vivo animal model approach, that Lcn2 is a potent
      inducer of mammary tumor growth but not a significant promoter of lung
      metastasis.

PMID- 20133631
TI  - Finding enzymes that are actively involved in cancer.

PMID- 20133632
TI  - Persistent hepatitis C virus infection in microscale primary human hepatocyte
      cultures.
AB  - Hepatitis C virus (HCV) remains a major public health problem, affecting
      approximately 130 million people worldwide. HCV infection can lead to cirrhosis,
      hepatocellular carcinoma, and end-stage liver disease, as well as extrahepatic
      complications such as cryoglobulinemia and lymphoma. Preventative and therapeutic
      options are severely limited; there is no HCV vaccine available, and nonspecific,
      IFN-based treatments are frequently ineffective. Development of targeted
      antivirals has been hampered by the lack of robust HCV cell culture systems that
      reliably predict human responses. Here, we show the entire HCV life cycle
      recapitulated in micropatterned cocultures (MPCCs) of primary human hepatocytes
      and supportive stroma in a multiwell format. MPCCs form polarized cell layers
      expressing all known HCV entry factors and sustain viral replication for several
      weeks. When coupled with highly sensitive fluorescence- and luminescence-based
      reporter systems, MPCCs have potential as a high-throughput platform for
      simultaneous assessment of in vitro efficacy and toxicity profiles of anti-HCV
      therapeutics.

PMID- 20133633
TI  - Neutrophil spontaneous death is mediated by down-regulation of autocrine
      signaling through GPCR, PI3Kgamma, ROS, and actin.
AB  - Neutrophil spontaneous apoptosis plays a crucial role in neutrophil homeostasis
      and the resolution of inflammation. We previously established Akt deactivation as
      a key mediator of this tightly regulated cellular death program. Nevertheless,
      the molecular mechanisms governing the diminished Akt activation were not
      characterized. Here, we report that Akt deactivation during the course of
      neutrophil spontaneous death was a result of reduced PtdIns(3,4,5)P3 level. The
      phosphatidylinositol lipid kinase activity of PI3Kgamma, but not class IA PI3Ks,
      was significantly reduced during neutrophil death. The production of
      PtdIns(3,4,5)P3 in apoptotic neutrophils was mainly maintained by autocrinely
      released chemokines that elicited PI3Kgamma activation via G protein-coupled
      receptors. Unlike in other cell types, serum-derived growth factors did not
      provide any survival advantage in neutrophils. PI3Kgamma, but not class IA PI3Ks,
      was negatively regulated by gradually accumulated ROS in apoptotic neutrophils,
      which suppressed PI3Kgamma activity by inhibiting an actin-mediated positive
      feedback loop. Taken together, these results provide insight into the mechanism
      of neutrophil spontaneous death and reveal a cellular pathway that regulates
      PtdIns(3,4,5)P3/Akt in neutrophils.

PMID- 20133634
TI  - Apurinic/apyrimidinic endonuclease APE1 is required for PACAP-induced
      neuroprotection against global cerebral ischemia.
AB  - Inducible DNA repair via the base-excision repair pathway is an important
      prosurvival mechanism activated in response to oxidative DNA damage. Elevated
      levels of the essential base-excision repair enzyme apurinic/apyrimidinic
      endonuclease 1 (APE1)/redox effector factor-1 correlate closely with neuronal
      survival against ischemic insults, depending on the CNS region, protective
      treatments, and degree of insult. However, the precise mechanisms by which this
      multifunctional protein affords protection and is activated by upstream signaling
      pathways in postischemic neurons are not well delineated. Here we show that
      intracerebral administration of pituitary adenylate cyclase-activating
      polypeptide (PACAP), an endogenously occurring small neuropeptide, induces
      expression of APE1 in hippocampal neurons. Induction of APE1 expression requires
      PKA- and p38-dependent phosphorylation of cAMP response-element binding and
      activating transcription factor 2, which leads to transactivation of the APE1
      promoter. We further show that PACAP markedly reduces oxidative DNA stress and
      hippocampal CA1 neuronal death following transient global ischemia. These effects
      occurred, at least in part, via enhanced APE1 expression. Furthermore, the DNA
      repair function of APE1 was required for PACAP-mediated neuroprotection. Thus,
      induction of DNA repair enzymes may be a unique strategy for neuroprotection
      against hippocampal injury.

PMID- 20133635
TI  - Innate immune detection of the type III secretion apparatus through the NLRC4
      inflammasome.
AB  - The mammalian innate immune system uses Toll-like receptors (TLRs) and Nod-LRRs
      (NLRs) to detect microbial components during infection. Often these molecules
      work in concert; for example, the TLRs can stimulate the production of the
      proforms of the cytokines IL-1beta and IL-18, whereas certain NLRs trigger their
      subsequent proteolytic processing via caspase 1. Gram-negative bacteria use type
      III secretion systems (T3SS) to deliver virulence factors to the cytosol of host
      cells, where they modulate cell physiology to favor the pathogen. We show here
      that NLRC4/Ipaf detects the basal body rod component of the T3SS apparatus (rod
      protein) from S. typhimurium (PrgJ), Burkholderia pseudomallei (BsaK),
      Escherichia coli (EprJ and EscI), Shigella flexneri (MxiI), and Pseudomonas
      aeruginosa (PscI). These rod proteins share a sequence motif that is essential
      for detection by NLRC4; a similar motif is found in flagellin that is also
      detected by NLRC4. S. typhimurium has two T3SS: Salmonella pathogenicity island-1
      (SPI1), which encodes the rod protein PrgJ, and SPI2, which encodes the rod
      protein SsaI. Although PrgJ is detected by NLRC4, SsaI is not, and this evasion
      is required for virulence in mice. The detection of a conserved component of the
      T3SS apparatus enables innate immune responses to virulent bacteria through a
      single pathway, a strategy that is divergent from that used by plants in which
      multiple NB-LRR proteins are used to detect T3SS effectors or their effects on
      cells. Furthermore, the specific detection of the virulence machinery permits the
      discrimination between pathogenic and nonpathogenic bacteria.

PMID- 20133636
TI  - Development and the evolvability of human limbs.
AB  - The long legs and short arms of humans are distinctive for a primate, the result
      of selection acting in opposite directions on each limb at different points in
      our evolutionary history. This mosaic pattern challenges our understanding of the
      relationship of development and evolvability because limbs are serially
      homologous and genetic correlations should act as a significant constraint on
      their independent evolution. Here we test a developmental model of limb
      covariation in anthropoid primates and demonstrate that both humans and apes
      exhibit significantly reduced integration between limbs when compared to
      quadrupedal monkeys. This result indicates that fossil hominins likely escaped
      constraints on independent limb variation via reductions to genetic pleiotropy in
      an ape-like last common ancestor (LCA). This critical change in integration among
      hominoids, which is reflected in macroevolutionary differences in the disparity
      between limb lengths, facilitated selection for modern human limb proportions and
      demonstrates how development helps shape evolutionary change.

PMID- 20133637
TI  - Downstream class switching leads to IgE antibody production by B lymphocytes
      lacking IgM switch regions.
AB  - Ig heavy chain (IgH) class-switch recombination (CSR) replaces the IgH C mu
      constant region exons with one of several sets of downstream IgH constant region
      exons (e.g., C gamma, C epsilon, or C alpha), which affects switching from IgM to
      another IgH class (e.g., IgG, IgE, or IgA). Activation-induced cytidine deaminase
      (AID) initiates CSR by promoting DNA double-strand breaks (DSBs) within switch
      (S) regions flanking the donor C mu (S mu) and a downstream acceptor C(H) (e.g.,
      S gamma, S epsilon, S alpha) that are then joined to complete CSR. DSBs generated
      in S mu frequently are joined within S mu to form internal switch region
      deletions (ISD). AID-induced ISD and mutations have been considered rare in
      downstream S regions, suggesting that AID targeting to these S regions requires
      its prior recruitment to S mu. We have now assayed for CSR and ISD in B cells
      lacking S mu (S mu(-/-) B cells). In S mu(-/-) B cells activated for CSR to IgG1
      and IgE, CSR to IgG1 was greatly reduced; but, surprisingly, CSR to IgE occurred
      at nearly normal levels. Moreover, normal B cells had substantial S gamma1 ISD
      and increased mutations in and near S gamma1, and levels of both were greatly
      increased in S mu(-/-) B cells. Finally, S mu(-/-) B cells underwent downstream
      CSR between S gamma1 and S epsilon on alleles that lacked S mu CSR to these
      sequences. Our findings show that AID targets downstream S regions independently
      of CSR with Smu and implicate an alternative pathway for IgE class switching that
      involves generation and joining of DSBs within two different downstream S regions
      before S mu joining.

PMID- 20133638
TI  - Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA
      integration.
AB  - Lens epithelium-derived growth factor (LEDGF) fusion proteins can direct HIV-1
      DNA integration to novel sites in the host genome. The C terminus of LEDGF
      contains an integrase binding domain (IBD), and the N terminus binds chromatin.
      LEDGF normally directs integrations to the bodies of expressed genes. Replacing
      the N terminus of LEDGF with chromatin binding domains (CBDs) from other proteins
      changes the specificity of HIV-1 DNA integration. We chose two well-characterized
      CBDs: the plant homeodomain (PHD) finger from ING2 and the chromodomain from
      heterochromatin binding protein 1alpha (HP1alpha). The ING2 PHD finger binds
      H3K4me3, a histone mark that is associated with the transcriptional start sites
      of expressed genes. The HP1alpha chromodomain binds H3K9me2,3, histone marks that
      are widely distributed throughout the genome. A fusion protein in which the ING2
      PHD finger was linked to the LEDGF IBD directed integrations near the start sites
      of expressed genes. A similar fusion protein in which the HP1alpha chromodomain
      was linked to the LEDGF IBD directed integrations to sites that differed from
      both the PHD finger fusion-directed and LEDGF-directed integration sites. The
      ability to redirect HIV-1 DNA integration may help solve the problems associated
      with the activation of oncogenes when retroviruses are used in gene therapy.

PMID- 20133639
TI  - Histone modification levels are predictive for gene expression.
AB  - Histones are frequently decorated with covalent modifications. These histone
      modifications are thought to be involved in various chromatin-dependent processes
      including transcription. To elucidate the relationship between histone
      modifications and transcription, we derived quantitative models to predict the
      expression level of genes from histone modification levels. We found that histone
      modification levels and gene expression are very well correlated. Moreover, we
      show that only a small number of histone modifications are necessary to
      accurately predict gene expression. We show that different sets of histone
      modifications are necessary to predict gene expression driven by high CpG content
      promoters (HCPs) or low CpG content promoters (LCPs). Quantitative models
      involving H3K4me3 and H3K79me1 are the most predictive of the expression levels
      in LCPs, whereas HCPs require H3K27ac and H4K20me1. Finally, we show that the
      connections between histone modifications and gene expression seem to be general,
      as we were able to predict gene expression levels of one cell type using a model
      trained on another one.

PMID- 20133640
TI  - Identification of an unconventional E3 binding surface on the UbcH5 ~ Ub
      conjugate recognized by a pathogenic bacterial E3 ligase.
AB  - Gram-negative bacteria deliver a cadre of virulence factors directly into the
      cytoplasm of eukaryotic host cells to promote pathogenesis and/or commensalism.
      Recently, families of virulence proteins have been recognized that function as E3
      Ubiquitin-ligases. How these bacterial ligases integrate into the ubiquitin (Ub)
      signaling pathways of the host and how they differ functionally from endogenous
      eukaryotic E3s is not known. Here we show that the bacterial E3 SspH2 from S.
      typhimurium selectively binds the human UbcH5 ~ Ub conjugate recognizing regions
      of both UbcH5 and Ub subunits. The surface of the E2 UbcH5 involved in this
      interaction differs substantially from that defined for other E2/E3 complexes
      involving eukaryotic E3-ligases. In vitro, SspH2 directs the synthesis of K48
      linked poly-Ub chains, suggesting that cellular protein targets of SspH2
      catalyzed Ub transfer are destined for proteasomal destruction. Unexpectedly, we
      found that intermediates in SspH2-directed reactions are activated poly-Ub chains
      directly tethered to the UbcH5 active site (UbcH5 ~ Ub(n)). Rapid generation of
      UbcH5 ~ Ub(n) may allow for bacterially directed modification of eukaryotic
      target proteins with a completed poly-Ub chain, efficiently tagging host targets
      for destruction.

PMID- 20133641
TI  - Mass spectrometry imaging of mating Tetrahymena show that changes in cell
      morphology regulate lipid domain formation.
AB  - Mass spectrometry imaging has been used here to suggest that changes in membrane
      structure drive lipid domain formation in mating single-cell organisms. Chemical
      studies of lipid bilayers in both living and model systems have revealed that
      chemical composition is coupled to localized membrane structure. However, it is
      not clear if the lipids that compose the membrane actively modify membrane
      structure or if structural changes cause heterogeneity in the surface chemistry
      of the lipid bilayer. We report that time-of-flight secondary ion mass
      spectrometry images of mating Tetrahymena thermophila acquired at various stages
      during mating demonstrate that lipid domain formation, identified as a decrease
      in the lamellar lipid phosphatidylcholine, follows rather than precedes
      structural changes in the membrane. Domains are formed in response to structural
      changes that occur during cell-to-cell conjugation. This observation has wide
      implications in all membrane processes.

PMID- 20133642
TI  - Structure and structural transition of chiral domains in oligo(p
      phenylenevinylene) assembly investigated by scanning tunneling microscopy.
AB  - OPV3-CHO molecules are employed to prepare assembly on highly oriented pyrolytic
      graphite, and the so-prepared assembly is investigated by scanning tunneling
      microscopy. In the assembly chiral domains are observed with various structures
      such as linear and windmill. The chiral structural formation, stability,
      transition, and possible unification are intensively studied. After thermal
      annealing, linear structure was the only structure. To achieve a unified assembly
      with a single structure, an efficient method is proposed by coadsorption of OPV3
      CHO with selected molecules. For example, an assembly with side-by-side helix
      structure is formed by a simple coadsorption of OPV3-CHO with alkyl bromide
      (C(n)H(2n+1)Br, n = 15-18). The experiments by cocrystallization of OPV3
      CHO/C(n)H(2n+1)X (X = Cl, Br, and I) show the important role of halogen bonding
      in formation of the uniform structure. The results are significant in
      understanding the intermolecular noncovalent interactions that dominate the
      surface structure and chirality.

PMID- 20133643
TI  - Ordered ferrimagnetic form of ferrihydrite reveals links among structure,
      composition, and magnetism.
AB  - The natural nanomineral ferrihydrite is an important component of many
      environmental and soil systems and has been implicated as the inorganic core of
      ferritin in biological systems. Knowledge of its basic structure, composition,
      and extent of structural disorder is essential for understanding its reactivity,
      stability, and magnetic behavior, as well as changes in these properties during
      aging. Here we investigate compositional, structural, and magnetic changes that
      occur upon aging of "2-line" ferrihydrite in the presence of adsorbed citrate at
      elevated temperature. Whereas aging under these conditions ultimately results in
      the formation of hematite, analysis of the atomic pair distribution function and
      complementary physicochemical and magnetic data indicate formation of an
      intermediate ferrihydrite phase of larger particle size with few defects, more
      structural relaxation and electron spin ordering, and pronounced ferrimagnetism
      relative to its disordered ferrihydrite precursor. Our results represent an
      important conceptual advance in understanding the nature of structural disorder
      in ferrihydrite and its relation to the magnetic structure and also serve to
      validate a controversial, recently proposed structural model for this phase. In
      addition, the pathway we identify for forming ferrimagnetic ferrihydrite
      potentially explains the magnetic enhancement that typically precedes formation
      of hematite in aerobic soil and weathering environments. Such magnetic
      enhancement has been attributed to the formation of poorly understood, nano-sized
      ferrimagnets from a ferrihydrite precursor. Whereas elevated temperatures drive
      the transformation on timescales feasible for laboratory studies, our results
      also suggest that ferrimagnetic ferrihydrite could form naturally at ambient
      temperature given sufficient time.

PMID- 20133644
TI  - Monoclonal antibody produced in plants efficiently treats West Nile virus
      infection in mice.
AB  - Over the past decade, West Nile virus (WNV) has spread to all 48 of the lower
      United States as well as to parts of Canada, Mexico, the Caribbean, and South
      America, with outbreaks of neuroinvasive disease occurring annually. At present,
      no therapeutic or vaccine is available for human use. Epidemics of WNV and other
      emerging infectious disease threats demand cost-efficient and scalable production
      technologies that can rapidly transfer effective therapeutics into the clinical
      setting. We have previously reported that Hu-E16, a humanized anti-WNV mAb, binds
      to a highly conserved epitope on the envelope protein, blocks viral fusion, and
      shows promising postexposure therapeutic activity. Herein, we generated a plant
      derived Hu-E16 mAb that can be rapidly scaled up for commercial production. Plant
      Hu-E16 was expressed at high levels within 8 days of infiltration in Nicotiana
      benthamiana plants and retained high-affinity binding and potent neutralizing
      activity in vitro against WNV. A single dose of plant Hu-E16 protected mice
      against WNV-induced mortality even 4 days after infection at rates that were
      indistinguishable from mammalian-cell-produced Hu-E16. This study demonstrates
      the efficacy of a plant-produced mAb against a potentially lethal infection
      several days after exposure in an animal challenge model and provides a proof of
      principle for the development of plant-derived mAbs as therapy against emerging
      infectious diseases.

PMID- 20133645
TI  - Fundamental signatures of short- and long-range electron transfer for the blue
      copper protein azurin at Au/SAM junctions.
AB  - The blue copper protein from Pseudomonas aeruginosa, azurin, immobilized at gold
      electrodes through hydrophobic interaction with alkanethiol self-assembled
      monolayers (SAMs) of the general type [-S-(CH(2))(n)-CH(3)] (n = 4, 10, and 15)
      was employed to gain detailed insight into the physical mechanisms of short- and
      long-range biomolecular electron transfer (ET). Fast scan cyclic voltammetry and
      a Marcus equation analysis were used to determine unimolecular standard rate
      constants and reorganization free energies for variable n, temperature (2-55
      degrees C), and pressure (5-150 MPa) conditions. A novel global fitting procedure
      was found to account for the reduced ET rate constant over almost five orders of
      magnitude (covering different n, temperature, and pressure) and revealed that
      electron exchange is a direct ET process and not conformationally gated. All the
      ET data, addressing SAMs with thickness variable over ca. 12 A, could be
      described by using a single reorganization energy (0.3 eV), however, the values
      for the enthalpies and volumes of activation were found to vary with n. These
      data and their comparison with theory show how to discriminate between the
      fundamental signatures of short- and long-range biomolecular ET that are
      theoretically anticipated for the adiabatic and nonadiabatic ET mechanisms,
      respectively.

PMID- 20133646
TI  - Plasmonic nanorod absorbers as orientation sensors.
AB  - Nanoparticles are actively exploited as biological imaging probes. Of particular
      interest are gold nanoparticles because of their nonblinking and nonbleaching
      absorption and scattering properties that arise from the excitation of surface
      plasmons. Nanoparticles with anisotropic shapes furthermore provide information
      about the probe orientation and its environment. Here we show how the orientation
      of single gold nanorods (25 x 73 nm) can be determined from both the transverse
      and longitudinal surface plasmon resonance by using polarization-sensitive
      photothermal imaging. By measuring the orientation of the same nanorods
      separately using scanning electron microscopy, we verified the high accuracy of
      this plasmon-absorption-based technique. However, care had to be taken when
      exciting the transverse plasmon absorption using a large numerical aperture
      objective as out-of-plane plasmon oscillations were also excited then. For the
      size regime studied here, being able to establish the nanorod orientation from
      the transverse mode is unique to photothermal imaging and almost impossible with
      conventional dark-field scattering spectroscopy. This is important because the
      transverse surface plasmon resonance is mostly insensitive to the medium
      refractive index and nanorod aspect ratio allowing nanorods of any length to be
      used as orientation sensors without changing the laser frequency.

PMID- 20133647
TI  - Electric field enhanced hydrogen storage on polarizable materials substrates.
AB  - Using density functional theory, we show that an applied electric field can
      substantially improve the hydrogen storage properties of polarizable substrates.
      This new concept is demonstrated by adsorbing a layer of hydrogen molecules on a
      number of nanomaterials. When one layer of H(2) molecules is adsorbed on a BN
      sheet, the binding energy per H(2) molecule increases from 0.03 eV/H(2) in the
      field-free case to 0.14 eV/H(2) in the presence of an electric field of 0.045
      a.u. The corresponding gravimetric density of 7.5 wt% is consistent with the 6
      wt% system target set by Department of Energy for 2010. The strength of the
      electric field can be reduced if the substrate is more polarizable. For example,
      a hydrogen adsorption energy of 0.14 eV/H(2) can be achieved by applying an
      electric field of 0.03 a.u. on an AlN substrate, 0.006 a.u. on a silsesquioxane
      molecule, and 0.007 a.u. on a silsesquioxane sheet. Thus, application of an
      electric field to a polarizable substrate provides a novel way to store hydrogen;
      once the applied electric field is removed, the stored H(2) molecules can be
      easily released, thus making storage reversible with fast kinetics. In addition,
      we show that materials with rich low-coordinated nonmetal anions are highly
      polarizable and can serve as a guide in the design of new hydrogen storage
      materials.

PMID- 20133648
TI  - Reactive collisions of sulfur dioxide with molten carbonates.
AB  - Molecular beam scattering experiments are used to investigate reactions of SO(2)
      at the surface of a molten alkali carbonate eutectic at 683 K. We find that two
      thirds of the SO(2) molecules that thermalize at the surface of the melt are
      converted to gaseous CO(2) via the reaction SO(2)(g) + CO(3)(2-) --> CO(2)(g) +
      SO(3)(-2). The CO(2) product is formed from SO(2) in less than 10(-6) s, implying
      that the reaction takes place in a shallow liquid region less than 100 A deep.
      The reaction probability does not vary between 683 and 883 K, further implying a
      compensation between decreasing SO(2) residence time in the near-interfacial
      region and increasing reactivity at higher temperatures. These results
      demonstrate the remarkable efficiency of SO(2) --> CO(2) conversion by molten
      carbonates, which appear to be much more reactive than dry calcium carbonate or
      wet slurries commonly used for flue gas desulfurization in coal-burning power
      plants.

PMID- 20133649
TI  - Molecular defects of the glycine 41 variants of alanine glyoxylate
      aminotransferase associated with primary hyperoxaluria type I.
AB  - G41 is an interfacial residue located within the alpha-helix 34-42 of
      alanine:glyoxylate aminotransferase (AGT). Its mutations on the major (AGT-Ma) or
      the minor (AGT-Mi) allele give rise to the variants G41R-Ma, G41R-Mi, and G41V-Ma
      causing hyperoxaluria type 1. Impairment of dimerization in these variants has
      been suggested to be responsible for immunoreactivity deficiency,
      intraperoxisomal aggregation, and sensitivity to proteasomal degradation.
      However, no experimental evidence supports this view. Here we report that G41
      mutations, besides increasing the dimer-monomer equilibrium dissociation
      constant, affect the protein conformation and stability, and perturb its active
      site. As compared to AGT-Ma or AGT-Mi, G41 variants display different near-UV CD
      and intrinsic emission fluorescence spectra, larger exposure of hydrophobic
      surfaces, sensitivity to Met53-Tyr54 peptide bond cleavage by proteinase K,
      decreased thermostability, reduced coenzyme binding affinity, and catalytic
      efficiency. Additionally, unlike AGT-Ma and AGT-Mi, G41 variants under
      physiological conditions form insoluble inactive high-order aggregates
      (approximately 5,000 nm) through intermolecular electrostatic interactions. A
      comparative molecular dynamics study of the putative structures of AGT-Mi and
      G41R-Mi predicts that G41 --> R mutation causes a partial unwinding of the 34-42
      alpha-helix and a displacement of the first 44 N-terminal residues including the
      active site loop 24-32. These simulations help us to envisage the possible
      structural basis of AGT dysfunction associated with G41 mutations. The detailed
      insight into how G41 mutations act on the structure-function of AGT may
      contribute to achieve the ultimate goal of correcting the effects of these
      mutations.

PMID- 20133650
TI  - Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for
      stimulation of lipogenesis, but not inhibition of gluconeogenesis.
AB  - The livers of insulin-resistant, diabetic mice manifest selective insulin
      resistance, suggesting a bifurcation in the insulin signaling pathway: Insulin
      loses its ability to block glucose production (i.e., it fails to suppress PEPCK
      and other genes of gluconeogenesis), yet it retains its ability to stimulate
      fatty acid synthesis (i.e., continued enhancement of genes of lipogenesis).
      Enhanced lipogenesis is accompanied by an insulin-stimulated increase in the mRNA
      encoding SREBP-1c, a transcription factor that activates the entire lipogenic
      program. Here, we report a branch point in the insulin signaling pathway that may
      account for selective insulin resistance. Exposure of rat hepatocytes to insulin
      produced a 25-fold increase in SREBP-1c mRNA and a 95% decrease in PEPCK mRNA.
      Insulin-mediated changes in both mRNAs were blocked by inhibitors of PI3K and
      Akt, indicating that these kinases are required for both pathways. In contrast,
      subnanomolar concentrations of rapamycin, an inhibitor of the mTORC1 kinase,
      blocked insulin induction of SREBP-1c, but had no effect on insulin suppression
      of PEPCK. We observed a similar selective effect of rapamycin in livers of rats
      and mice that experienced an insulin surge in response to a fasting-refeeding
      protocol. A specific inhibitor of S6 kinase, a downstream target of mTORC1, did
      not block insulin induction of SREBP-1c, suggesting a downstream pathway distinct
      from S6 kinase. These results establish mTORC1 as an essential component in the
      insulin-regulated pathway for hepatic lipogenesis but not gluconeogenesis, and
      may help to resolve the paradox of selective insulin resistance in livers of
      diabetic rodents.

PMID- 20133651
TI  - Crystal structure of the bifunctional proline utilization A flavoenzyme from
      Bradyrhizobium japonicum.
AB  - The bifunctional proline catabolic flavoenzyme, proline utilization A (PutA),
      catalyzes the oxidation of proline to glutamate via the sequential activities of
      FAD-dependent proline dehydrogenase (PRODH) and NAD(+)-dependent Delta(1)
      pyrroline-5-carboxylate dehydrogenase (P5CDH) domains. Although structures for
      some of the domains of PutA are known, a structure for the full-length protein
      has not previously been solved. Here we report the 2.1 A resolution crystal
      structure of PutA from Bradyrhizobium japonicum, along with data from small-angle
      x-ray scattering, analytical ultracentrifugation, and steady-state and rapid
      reaction kinetics. PutA forms a ring-shaped tetramer in solution having a
      diameter of 150 A. Within each protomer, the PRODH and P5CDH active sites face
      each other at a distance of 41 A and are connected by a large, irregularly shaped
      cavity. Kinetics measurements show that glutamate production occurs without a lag
      phase, suggesting that the intermediate, Delta(1)-pyrroline-5-carboxylate, is
      preferably transferred to the P5CDH domain rather than released into the bulk
      medium. The structural and kinetic data imply that the cavity serves both as a
      microscopic vessel for the hydrolysis of Delta(1)-pyrroline-5-carboxylate to
      glutamate semialdehyde and a protected conduit for the transport of glutamate
      semialdehyde to the P5CDH active site.

PMID- 20133652
TI  - Transport and signaling through the phosphate-binding site of the yeast Pho84
      phosphate transceptor.
AB  - A novel concept in eukaryotic signal transduction is the use of nutrient
      transporters and closely related proteins as nutrient sensors. The action
      mechanism of these "transceptors" is unclear. The Pho84 phosphate transceptor in
      yeast transports phosphate and mediates rapid phosphate activation of the protein
      kinase A (PKA) pathway during growth induction. We have now identified several
      phosphate-containing compounds that act as nontransported signaling agonists of
      Pho84. This indicates that signaling does not require complete transport of the
      substrate. For the nontransported agonist glycerol-3-phosphate (Gly3P), we show
      that it is transported by two other carriers, Git1 and Pho91, without triggering
      signaling. Gly3P is a competitive inhibitor of transport through Pho84,
      indicating direct interaction with its phosphate-binding site. We also identified
      phosphonoacetic acid as a competitive inhibitor of transport without agonist
      function for signaling. This indicates that binding of a compound into the
      phosphate-binding site of Pho84 is not enough to trigger signaling. Apparently,
      signaling requires a specific conformational change that may be part of, but does
      not require, the complete transport cycle. Using Substituted Cysteine
      Accessibility Method (SCAM) we identified Phe(160) in TMD IV and Val(392) in TMD
      VIII as residues exposed with their side chain into the phosphate-binding site of
      Pho84. Inhibition of both transport and signaling by covalent modification of
      Pho84(F160C) or Pho84(V392C) showed that the same binding site is used for
      transport of phosphate and for signaling with both phosphate and Gly3P. Our
      results provide to the best of our knowledge the first insight into the molecular
      mechanism of a phosphate transceptor.

PMID- 20133653
TI  - No difference in kinetics of tau or histone phosphorylation by CDK5/p25 versus
      CDK5/p35 in vitro.
AB  - CDK5/p35 is a cyclin-dependent kinase essential for normal neuron function.
      Proteolysis of the p35 subunit in vivo results in CDK5/p25 that causes
      neurotoxicity associated with a number of neurodegenerative diseases. Whereas the
      mechanism by which conversion of p35 to p25 leads to toxicity is unknown, there
      is common belief that CDK5/p25 is catalytically hyperactive compared to CDK5/p35.
      Here, we have compared the steady-state kinetic parameters of CDK5/p35 and
      CDK5/p25 towards both histone H1, the best known substrate for both enzymes, and
      the microtubule-associated protein, tau, a physiological substrate whose in vivo
      phosphorylation is relevant to Alzheimer's disease. We show that the kinetics of
      both enzymes are the same towards either substrate in vitro. Furthermore, both
      enzymes display virtually identical kinetics towards individual phosphorylation
      sites in tau monitored by NMR. We conclude that conversion of p35 to p25 does not
      alter the catalytic efficiency of the CDK5 catalytic subunit by using histone H1
      or tau as substrates, and that neurotoxicity associated with CDK5/p25 is unlikely
      attributable to CDK5 hyperactivation, as measured in vitro.

PMID- 20133654
TI  - Structural insight into M-band assembly and mechanics from the titin-obscurin
      like-1 complex.
AB  - In the sarcomeric M-band, the giant ruler proteins titin and obscurin, its small
      homologue obscurin-like-1 (obsl1), and the myosin cross-linking protein myomesin
      form a ternary complex that is crucial for the function of the M-band as a
      mechanical link. Mutations in the last titin immunoglobulin (Ig) domain M10,
      which interacts with the N-terminal Ig-domains of obscurin and obsl1, lead to
      hereditary muscle diseases. The M10 domain is unusual not only in that it is a
      frequent target of disease-linked mutations, but also in that it is the only
      currently known muscle Ig-domain that interacts with two ligands--obscurin and
      obsl1--in different sarcomeric subregions. Using x-ray crystallography, we show
      the structural basis for titin M10 interaction with obsl1 in a novel antiparallel
      Ig-Ig architecture and unravel the molecular basis of titin-M10 linked
      myopathies. The severity of these pathologies correlates with the disruption of
      the titin-obsl1/obscurin complex. Conserved signature residues at the interface
      account for differences in affinity that direct the cellular sorting in
      cardiomyocytes. By engineering the interface signature residues of obsl1 to
      obscurin, and vice versa, their affinity for titin can be modulated similar to
      the native proteins. In single-molecule force-spectroscopy experiments, both
      complexes yield at forces of around 30 pN, much lower than those observed for the
      mechanically stable Z-disk complex of titin and telethonin, suggesting why even
      moderate weakening of the obsl1/obscurin-titin links has severe consequences for
      normal muscle functions.

PMID- 20133655
TI  - Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation
      of virulence genes.
AB  - Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae.
      In order for V. cholerae to cause disease, it must produce two virulence factors,
      the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is
      controlled by a transcriptional cascade culminating with the expression of the
      AraC-family regulator, ToxT. We have solved the 1.9 A resolution crystal
      structure of ToxT, which reveals folds in the N- and C-terminal domains that
      share a number of features in common with AraC, MarA, and Rob as well as the
      unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The
      finding that cis-palmitoleic acid reduces TCP and CT expression in V. cholerae
      and prevents ToxT from binding to DNA in vitro provides a direct link between the
      host environment of V. cholerae and regulation of virulence gene expression.

PMID- 20133656
TI  - Inhibitory role for GABA in autoimmune inflammation.
AB  - GABA, the principal inhibitory neurotransmitter in the adult brain, has a
      parallel inhibitory role in the immune system. We demonstrate that immune cells
      synthesize GABA and have the machinery for GABA catabolism. Antigen-presenting
      cells (APCs) express functional GABA receptors and respond electrophysiologically
      to GABA. Thus, the immune system harbors all of the necessary constituents for
      GABA signaling, and GABA itself may function as a paracrine or autocrine factor.
      These observations led us to ask further whether manipulation of the GABA pathway
      influences an animal model of multiple sclerosis, experimental autoimmune
      encephalomyelitis (EAE). Increasing GABAergic activity ameliorates ongoing
      paralysis in EAE via inhibition of inflammation. GABAergic agents act directly on
      APCs, decreasing MAPK signals and diminishing subsequent adaptive inflammatory
      responses to myelin proteins.

PMID- 20133657
TI  - Estrogen receptor-beta activated apoptosis in benign hyperplasia and cancer of
      the prostate is androgen independent and TNFalpha mediated.
AB  - Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen
      dependent diseases commonly treated by inhibiting androgen action. However,
      androgen ablation or castration fail to target androgen-independent cells
      implicated in disease etiology and recurrence. Mechanistically different to
      castration, this study shows beneficial proapoptotic actions of estrogen receptor
      beta (ERbeta) in BPH and PCa. ERbeta agonist induces apoptosis in prostatic
      stromal, luminal and castrate-resistant basal epithelial cells of estrogen
      deficient aromatase knock-out mice. This occurs via extrinsic (caspase-8)
      pathways, without reducing serum hormones, and perturbs the regenerative capacity
      of the epithelium. TNFalpha knock-out mice fail to respond to ERbeta agonist,
      demonstrating the requirement for TNFalpha signaling. In human tissues, ERbeta
      agonist induces apoptosis in stroma and epithelium of xenografted BPH specimens,
      including in the CD133(+) enriched putative stem/progenitor cells isolated from
      BPH-1 cells in vitro. In PCa, ERbeta causes apoptosis in Gleason Grade 7
      xenografted tissues and androgen-independent cells lines (PC3 and DU145) via
      caspase-8. These data provide evidence of the beneficial effects of ERbeta
      agonist on epithelium and stroma of BPH, as well as androgen-independent tumor
      cells implicated in recurrent disease. Our data are indicative of the therapeutic
      potential of ERbeta agonist for treatment of PCa and/or BPH with or without
      androgen withdrawal.

PMID- 20133658
TI  - Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates
      rhabdomyolysis-induced renal failure.
AB  - Hemoproteins, hemoglobin and myoglobin, once released from cells can cause severe
      oxidative damage as a consequence of heme redox cycling between ferric and ferryl
      states that generates radical species that induce lipid peroxidation. We
      demonstrate in vitro that acetaminophen inhibits hemoprotein-induced lipid
      peroxidation by reducing ferryl heme to its ferric state and quenching globin
      radicals. Severe muscle injury (rhabdomyolysis) is accompanied by the release of
      myoglobin that becomes deposited in the kidney, causing renal injury. We
      previously showed in a rat model of rhabdomyolysis that redox cycling between
      ferric and ferryl myoglobin yields radical species that cause severe oxidative
      damage to the kidney. In this model, acetaminophen at therapeutic plasma
      concentrations significantly decreased oxidant injury in the kidney, improved
      renal function, and reduced renal damage. These findings also provide a
      hypothesis for potential therapeutic applications for acetaminophen in diseases
      involving hemoprotein-mediated oxidative injury.

PMID- 20133659
TI  - Analysis of a gain-of-function FGFR2 Crouzon mutation provides evidence of loss
      of function activity in the etiology of cleft palate.
AB  - Cleft palate is a common birth defect in humans and is a common phenotype
      associated with syndromic mutations in fibroblast growth factor receptor 2
      (Fgfr2). Cleft palate occurred in nearly all mice homozygous for the Crouzon
      syndrome mutation C342Y in the mesenchymal splice form of Fgfr2. Mutant embryos
      showed delayed palate elevation, stage-specific biphasic changes in palate
      mesenchymal proliferation, and reduced levels of mesenchymal glycosaminoglycans
      (GAGs). Reduced levels of feedback regulators of FGF signaling suggest that this
      gain-of-function mutation in FGFR2 ultimately resembles loss of FGF function in
      palate mesenchyme. Knowledge of how mesenchymal FGF signaling regulates palatal
      shelf development may ultimately lead to pharmacological approaches to reduce
      cleft palate incidence in genetically predisposed humans.

PMID- 20133660
TI  - Logistical feasibility and potential benefits of a population-wide passive
      immunotherapy program during an influenza pandemic.
AB  - Treatment strategies for severe cases of pandemic influenza have focused on
      antiviral therapies. In contrast, passive immunotherapy with convalescent blood
      products has received limited attention. We consider the hypothesis that a
      passive-immunotherapy program that collects plasma from a small percentage of
      recovered adults can harvest sufficient convalescent plasma to treat a
      substantial percentage of severe cases during a pandemic. We use a mathematical
      model to estimate the demand and supply of passive immunotherapy during an
      influenza pandemic in Hong Kong. If >5% of 20- to 55-year-old individuals
      recovered from symptomatic infection donate their plasma (donor percentage > 5%),
      >67% of severe cases can be offered convalescent plasma transfusion (treatment
      coverage > 67%) in a moderately severe epidemic (R (0) < 1.4 with 0.5% of
      symptomatic cases becoming severe). A donor percentage of 5% is comparable to the
      average blood donation rate of 38.1 donations per 1,000 people in developed
      countries. Increasing the donor percentage above 15% does not significantly boost
      the convalescent plasma supply because supply is constrained by plasmapheresis
      capacity during most stages of the epidemic. The demand-supply balance depends on
      the natural history and transmission dynamics of the disease via the epidemic
      growth rate only. Compared to other major cities, Hong Kong has a low
      plasmapheresis capacity. Therefore, the proposed passive-immunotherapy program is
      a logistically feasible mitigation option for many developed countries. As such,
      passive immunotherapy deserves more consideration by clinical researchers
      regarding its safety and efficacy as a treatment for severe cases of pandemic
      influenza.

PMID- 20133661
TI  - Enhancement of fruit shelf life by suppressing N-glycan processing enzymes.
AB  - In a globalized economy, the control of fruit ripening is of strategic importance
      because excessive softening limits shelf life. Efforts have been made to reduce
      fruit softening in transgenic tomato through the suppression of genes encoding
      cell wall-degrading proteins. However, these have met with very limited success.
      N-glycans are reported to play an important role during fruit ripening, although
      the role of any particular enzyme is yet unknown. We have identified and targeted
      two ripening-specific N-glycoprotein modifying enzymes, alpha-mannosidase (alpha
      Man) and beta-D-N-acetylhexosaminidase (beta-Hex). We show that their suppression
      enhances fruit shelf life, owing to the reduced rate of softening. Analysis of
      transgenic tomatoes revealed approximately 2.5- and approximately 2-fold firmer
      fruits in the alpha-Man and beta-Hex RNAi lines, respectively, and approximately
      30 days of enhanced shelf life. Overexpression of alpha-Man or beta-Hex resulted
      in excessive fruit softening. Expression of alpha-Man and beta-Hex is induced by
      the ripening hormone ethylene and is modulated by a regulator of ripening, rin
      (ripening inhibitor). Furthermore, transcriptomic comparative studies demonstrate
      the down-regulation of cell wall degradation- and ripening-related genes in RNAi
      fruits. It is evident from these results that N-glycan processing is involved in
      ripening-associated fruit softening. Genetic manipulation of N-glycan processing
      can be of strategic importance to enhance fruit shelf life, without any negative
      effect on phenotype, including yield.

PMID- 20133662
TI  - Energized outer membrane and spatial separation of metabolic processes in the
      hyperthermophilic Archaeon Ignicoccus hospitalis.
AB  - ATP synthase catalyzes ATP synthesis at the expense of an electrochemical ion
      gradient across a membrane that can be generated by different exergonic
      reactions. Sulfur reduction is the main energy-yielding reaction in the
      hyperthermophilic strictly anaerobic Crenarchaeon Ignicoccus hospitalis. This
      organism is unusual in having an inner and an outer membrane that are separated
      by a huge intermembrane compartment. Here we show, on the basis of immuno-EM
      analyses of ultrathin sections and immunofluorescence experiments with whole I.
      hospitalis cells, that the ATP synthase and H(2):sulfur oxidoreductase complexes
      of this organism are located in the outer membrane. These two enzyme complexes
      are mandatory for the generation of an electrochemical gradient and for ATP
      synthesis. Thus, among all prokaryotes possessing two membranes in their cell
      envelope (including Planctomycetes, gram-negative bacteria), I. hospitalis is a
      unique organism, with an energized outer membrane and ATP synthesis within the
      periplasmic space. In addition, DAPI staining and EM analyses showed that DNA and
      ribosomes are localized in the cytoplasm, leading to the conclusion that in I.
      hospitalis energy conservation is separated from information processing and
      protein biosynthesis. This raises questions regarding the function of the two
      membranes, the interaction between these compartments, and the general definition
      of a cytoplasmic membrane.

PMID- 20133663
TI  - Compartmentalization by directional gene expression.
AB  - The coalescence of basic biochemical reactions into compartments is a major
      hallmark of a living cell. Using surface-bound DNA and a transcription reaction,
      we investigate the conditions for boundary-free compartmentalization. The DNA
      self-organizes into a dense and ordered phase with coding sequences aligned at
      well-defined distances and orientation relative to the surface, imposing
      directionality on transcription. Unique to the surface in comparison to dilute
      homogeneous DNA solution, the reaction slows down early, is inhibited with
      increased DNA density, is favorable for surface-oriented promoters, and is robust
      against DNA condensation. We interpret these results to suggest that
      macromolecules (RNA polymerase and RNA), but not solutes (ions and nucleotides),
      are partitioned between immobilized DNA and the reservoir. Without any physical
      barrier, a nonequilibrium directional DNA transaction forms macromolecular
      gradients that define a compartment, thus offering a boundary-free approach to
      the assembly of a synthetic cell.

PMID- 20133664
TI  - The transition state for folding of an outer membrane protein.
AB  - Inspired by the seminal work of Anfinsen, investigations of the folding of small
      water-soluble proteins have culminated in detailed insights into how these
      molecules attain and stabilize their native folds. In contrast, despite their
      overwhelming importance in biology, progress in understanding the folding and
      stability of membrane proteins remains relatively limited. Here we use mutational
      analysis to describe the transition state involved in the reversible folding of
      the beta-barrel membrane protein PhoPQ-activated gene P (PagP) from a highly
      disordered state in 10 M urea to a native protein embedded in a lipid bilayer.
      Analysis of the equilibrium stability and unfolding kinetics of 19 variants that
      span all eight beta-strands of this 163-residue protein revealed that the
      transition-state structure is a highly polarized, partly formed beta-barrel. The
      results provide unique and detailed insights into the transition-state structure
      for beta-barrel membrane protein folding into a lipid bilayer and are consistent
      with a model for outer membrane protein folding via a tilted insertion mechanism.

PMID- 20133665
TI  - Predicting strength and function for promoters of the Escherichia coli
      alternative sigma factor, sigmaE.
AB  - Sequenced bacterial genomes provide a wealth of information but little
      understanding of transcriptional regulatory circuits largely because accurate
      prediction of promoters is difficult. We examined two important issues for
      accurate promoter prediction: (1) the ability to predict promoter strength and
      (2) the sequence properties that distinguish between active and weak/inactive
      promoters. We addressed promoter prediction using natural core promoters
      recognized by the well-studied alternative sigma factor, Escherichia coli
      sigma(E), as a representative of group 4 sigmas, the largest sigma group. To
      evaluate the contribution of sequence to promoter strength and function, we used
      modular position weight matrix models comprised of each promoter motif and a
      penalty score for suboptimal motif location. We find that a combination of select
      modules is moderately predictive of promoter strength and that imposing minimal
      motif scores distinguished active from weak/inactive promoters. The combined -35/
      10 score is the most important predictor of activity. Our models also identified
      key sequence features associated with active promoters. A conserved "AAC" motif
      in the -35 region is likely to be a general predictor of function for promoters
      recognized by group 4 sigmas. These results provide valuable insights into
      sequences that govern promoter strength, distinguish active and inactive
      promoters for the first time, and are applicable to both in vivo and in vitro
      measures of promoter strength.

PMID- 20133666
TI  - Supramolecular design of self-assembling nanofibers for cartilage regeneration.
AB  - Molecular and supramolecular design of bioactive biomaterials could have a
      significant impact on regenerative medicine. Ideal regenerative therapies should
      be minimally invasive, and thus the notion of self-assembling biomaterials
      programmed to transform from injectable liquids to solid bioactive structures in
      tissue is highly attractive for clinical translation. We report here on a
      coassembly system of peptide amphiphile (PA) molecules designed to form
      nanofibers for cartilage regeneration by displaying a high density of binding
      epitopes to transforming growth factor beta-1 (TGFbeta-1). Growth factor release
      studies showed that passive release of TGFbeta-1 was slower from PA gels
      containing the growth factor binding sites. In vitro experiments indicate these
      materials support the survival and promote the chondrogenic differentiation of
      human mesenchymal stem cells. We also show that these materials can promote
      regeneration of articular cartilage in a full thickness chondral defect treated
      with microfracture in a rabbit model with or even without the addition of
      exogenous growth factor. These results demonstrate the potential of a completely
      synthetic bioactive biomaterial as a therapy to promote cartilage regeneration.

PMID- 20133667
TI  - Competing feedback loops shape IL-2 signaling between helper and regulatory T
      lymphocytes in cellular microenvironments.
AB  - Cytokines are pleiotropic and readily diffusible messenger molecules, raising the
      question of how their action can be confined to specific target cells. The T cell
      cytokine interleukin-2 (IL-2) is essential for the homeostasis of regulatory T
      (Treg) cells that suppress (auto)immunity and stimulates immune responses
      mediated by conventional T cells. We combined mathematical modeling and
      experiments to dissect the dynamics of the IL-2 signaling network that links the
      prototypical IL-2 producers, conventional T helper (Th) cells, and Treg cells. We
      show how the IL-2-induced upregulation of high-affinity IL-2 receptors (IL-2R)
      establishes a positive feedback loop of IL-2 signaling. This feedback mediates a
      digital switch for the proliferation of Th cells and functions as an analog
      amplifier for the IL-2 uptake capacity of Treg cells. Unlike other positive
      feedbacks in cell signaling that augment signal propagation, the IL-2/IL-2R loop
      enhances the capture of the signal molecule and its degradation. Thus Treg and Th
      cells can compete for IL-2 and restrict its range of action through efficient
      cellular uptake. Depending on activation status and spatial localization of the
      cells, IL-2 may be consumed exclusively by Treg or Th cells, or be shared between
      them. In particular, a Treg cell can deprive a stimulated Th cell of its IL-2,
      but only when the cells are located in close proximity, within a few tens of
      micrometers. The present findings explain how IL-2 can play two distinct roles in
      immune regulation and point to a hitherto largely unexplored spatiotemporal
      complexity of cytokine signaling.

PMID- 20133668
TI  - Making short-term climate forecasts useful: Linking science and action.
AB  - This paper discusses the evolution of scientific and social understanding that
      has led to the development of knowledge systems supporting the application of El
      Nino-Southern Oscillation (ENSO) forecasts, including the development of
      successful efforts to connect climate predictions with sectoral applications and
      actions "on the ground". The evolution of "boundary-spanning" activities to
      connect science and decisionmaking is then discussed, setting the stage for a
      report of outcomes from an international workshop comprised of producers,
      translators, and users of climate predictions. The workshop, which focused on
      identifying critical boundary-spanning features of successful boundary
      organizations, included participants from Australia, Hawaii, and the Pacific
      Islands, the US Pacific Northwest, and the state of Ceara in northwestern Brazil.
      Workshop participants agreed that boundary organizations have multiple roles
      including those of information broker, convenor of forums for engagement,
      translator of scientific information, arbiter of access to knowledge, and
      exemplar of adaptive behavior. Through these roles, boundary organizations will
      ensure the stability of the knowledge system in a changing political, economic,
      and climatic context. The international examples reviewed in this workshop
      demonstrated an interesting case of convergent evolution, where organizations
      that were very different in origin evolved toward similar structures and
      individuals engaged in them had similar experiences to share. These examples
      provide evidence that boundary organizations and boundary-spanners fill some
      social/institutional roles that are independent of culture. 

PMID- 20133669
TI  - Prolonged sensory-selective nerve blockade.
AB  - Sensory-selective local anesthesia has long been a key goal in local anesthetic
      development. For example, it allows women to be pain-free during labor without
      compromising their ability to push. Here we show that prolonged sensory-selective
      nerve block can be produced by specific concentrations of surfactants-such as are
      used to enhance drug flux across skin-in combination with QX-314, a lidocaine
      derivative that has relative difficulty penetrating nerves. For example,
      injection of 25 mM QX-314 in 30 mM octyltrimethylammonium bromide (OTAB) lasted
      up to 7 h. Sensory selectivity was imparted to varying degrees by cationic,
      neutral, and anionic surfactants, and also was achieved with another lidocaine
      derivative, QX-222. Simultaneous injection of OTAB at a s.c. injection site
      remote from the sciatic nerve did not result in prolonged sensory-specific nerve
      blockade from QX-314, suggesting that the observed effect is due to a local
      interaction between the surfactant and the lidocaine derivative, not a systemic
      effect.

PMID- 20133670
TI  - Local adaptation in Trinidadian guppies alters ecosystem processes.
AB  - Theory suggests evolutionary change can significantly influence and act in tandem
      with ecological forces via ecological-evolutionary feedbacks. This theory assumes
      that significant evolutionary change occurs over ecologically relevant timescales
      and that phenotypes have differential effects on the environment. Here we test
      the hypothesis that local adaptation causes ecosystem structure and function to
      diverge. We demonstrate that populations of Trinidadian guppies (Poecilia
      reticulata), characterized by differences in phenotypic and population-level
      traits, differ in their impact on ecosystem properties. We report results from a
      replicated, common garden mesocosm experiment and show that differences between
      guppy phenotypes result in the divergence of ecosystem structure (algal,
      invertebrate, and detrital standing stocks) and function (gross primary
      productivity, leaf decomposition rates, and nutrient flux). These phenotypic
      effects are further modified by effects of guppy density. We evaluated the
      generality of these effects by replicating the experiment using guppies derived
      from two independent origins of the phenotype. Finally, we tested the ability of
      multiple guppy traits to explain observed differences in the mesocosms. Our
      findings demonstrate that evolution can significantly affect both ecosystem
      structure and function. The ecosystem differences reported here are consistent
      with patterns observed across natural streams and argue that guppies play a
      significant role in shaping these ecosystems.

PMID- 20133671
TI  - MYC regulation of a "poor-prognosis" metastatic cancer cell state.
AB  - Gene expression signatures are used in the clinic as prognostic tools to
      determine the risk of individual patients with localized breast tumors developing
      distant metastasis. We lack a clear understanding, however, of whether these
      correlative biomarkers link to a common biological network that regulates
      metastasis. We find that the c-MYC oncoprotein coordinately regulates the
      expression of 13 different "poor-outcome" cancer signatures. In addition,
      functional inactivation of MYC in human breast cancer cells specifically inhibits
      distant metastasis in vivo and invasive behavior in vitro of these cells. These
      results suggest that MYC oncogene activity (as marked by "poor-prognosis"
      signature expression) may be necessary for the translocation of poor-outcome
      human breast tumors to distant sites.

PMID- 20133672
TI  - Placental-specific Igf2 knockout mice exhibit hypocalcemia and adaptive changes
      in placental calcium transport.
AB  - Evidence is emerging that the ability of the placenta to supply nutrients to the
      developing fetus adapts according to fetal demand. To examine this adaptation
      further, we tested the hypothesis that placental maternofetal transport of
      calcium adapts according to fetal calcium requirements. We used a mouse model of
      fetal growth restriction, the placental-specific Igf2 knockout (P0) mouse, shown
      previously to transiently adapt placental System-A amino acid transporter
      activity relative to fetal growth. Fetal and placental weights in P0 mice were
      reduced when compared with WT at both embryonic day 17 (E17) and E19. Ionized
      calcium concentration [Ca(2+)] was significantly lower in P0 fetal blood compared
      with both WT and maternal blood at E17 and E19, reflecting a reversal of the
      fetomaternal [Ca(2+)] gradient. Fetal calcium content was reduced in P0 mice at
      E17 but not at E19. Unidirectional maternofetal calcium clearance ((Ca) K (mf))
      was not different between WT and P0 at E17 but increased in P0 at E19. Expression
      of the intracellular calcium-binding protein calbindin-D(9K), previously shown to
      be rate-limiting for calcium transport, was increased in P0 relative to WT
      placentas between E17 and E19. These data show an increased placental transport
      of calcium from E17 to E19 in P0 compared to WT. We suggest that this is an
      adaptation in response to the reduced fetal calcium accumulation earlier in
      gestation and speculate that the ability of the placenta to adapt its supply
      capacity according to fetal demand may stretch across other essential nutrients.

PMID- 20133673
TI  - Impaired geometric reorientation caused by genetic defect.
AB  - The capacity to reorient in one's environment is a fundamental part of the
      spatial cognitive systems of both humans and nonhuman species. Abundant
      literature has shown that human adults and toddlers, rats, chicks, and fish
      accomplish reorientation through the construction and use of geometric
      representations of surrounding layouts, including the lengths of surfaces and
      their intersection. Does the development of this reorientation system rely on
      specific genes and their action in brain development? We tested reorientation in
      individuals who have Williams syndrome (WS), a genetic disorder that results in
      abnormalities of hippocampal and parietal areas of the brain known to be involved
      in reorientation. We found that in a rectangular chamber devoid of surface
      feature information, WS individuals do not use the geometry of the chamber to
      reorient, failing to find a hidden object. The failure among people with WS
      cannot be explained by more general deficits in visual-spatial working memory, as
      the same individuals performed at ceiling in a similar task in which they were
      not disoriented. We also found that performance among people with WS improves in
      a rectangular chamber with one blue wall, suggesting that some individuals with
      WS can use the blue wall feature to locate the hidden object. These results show
      that the geometric system used for reorientation in humans can be selectively
      damaged by specific genetic and neural abnormalities in humans.

PMID- 20133674
TI  - Binding and uptake of H-ferritin are mediated by human transferrin receptor-1.
AB  - Ferritin is a spherical molecule composed of 24 subunits of two types, ferritin H
      chain (FHC) and ferritin L chain (FLC). Ferritin stores iron within cells, but it
      also circulates and binds specifically and saturably to a variety of cell types.
      For most cell types, this binding can be mediated by ferritin composed only of
      FHC (HFt) but not by ferritin composed only of FLC (LFt), indicating that binding
      of ferritin to cells is mediated by FHC but not FLC. By using expression cloning,
      we identified human transferrin receptor-1 (TfR1) as an important receptor for
      HFt with little or no binding to LFt. In vitro, HFt can be precipitated by
      soluble TfR1, showing that this interaction is not dependent on other proteins.
      Binding of HFt to TfR1 is partially inhibited by diferric transferrin, but it is
      hindered little, if at all, by HFE. After binding of HFt to TfR1 on the cell
      surface, HFt enters both endosomes and lysosomes. TfR1 accounts for most, if not
      all, of the binding of HFt to mitogen-activated T and B cells, circulating
      reticulocytes, and all cell lines that we have studied. The demonstration that
      TfR1 can bind HFt as well as Tf raises the possibility that this dual receptor
      function may coordinate the processing and use of iron by these iron-binding
      molecules.

PMID- 20133675
TI  - Inverted-U-shaped correlation between dopamine receptor availability in striatum
      and sensation seeking.
AB  - Sensation seeking is a core personality trait that declines with age in both men
      and women, as do also both density and availability of the dopamine D(2/3)
      receptors in striatum and cortical regions. In contrast, novelty seeking at a
      given age relates inversely to dopamine receptor availability. The simplest
      explanation of these findings is an inverted-U-shaped correlation between ratings
      of sensation seeking on the Zuckerman scale and dopamine D(2/3) receptor
      availability. To test the claim of an inverted-U-shaped relation between ratings
      of the sensation-seeking personality and measures of dopamine receptor
      availability, we used PET to record [(11)C]raclopride binding in striatum of 18
      healthy men. Here we report that an inverted-U shape significantly matched the
      receptor availability as a function of the Zuckerman score, with maximum binding
      potentials observed in the midrange of the scale. The inverted-U shape is
      consistent with a negative correlation between sensation seeking and the
      reactivity ("gain") of dopaminergic neurotransmission to dopamine. The
      correlation reflects Zuckerman scores that are linearly linked to dopamine
      receptor densities in the striatum but nonlinearly linked to dopamine
      concentrations. Higher dopamine occupancy and dopamine concentrations explain the
      motivation that drives afflicted individuals to seek sensations, in agreement
      with reduced protection against addictive behavior that is characteristic of
      individuals with low binding potentials.

PMID- 20133676
TI  - Subcellular dynamics of T cell immunological synapses and kinapses in lymph
      nodes.
AB  - In vitro studies have revealed that T cell activation occurs during the formation
      of either dynamic or stable interactions with antigen-presenting cells (APC), and
      the respective cell junctions have been referred to as immunological kinapses and
      synapses. However, the relevance and molecular dynamics of kinapses and synapses
      remain to be established in vivo. Using two-photon imaging, we tracked the
      distribution of LAT-EGFP molecules during antigen recognition by activated CD4(+)
      T cells in lymph nodes. At steady state, LAT-EGFP molecules were preferentially
      found at the uropod of rapidly migrating T cells. In contrast to naive T cells
      that fully stopped upon systemic antigen delivery, recently activated T cells
      decelerated and formed kinapses, characterized by continuous extension of
      membrane protrusions and by the absence of persistent LAT-EGFP clustering. On the
      other hand, activated CD4(+) T cells formed stable immunological synapses with
      antigen-loaded B cells and displayed sustained accumulation of LAT-EGFP
      fluorescence at the contact zone. Our results show that the state of T cell
      activation and the type of APC largely influence T cell-APC contact dynamics in
      lymph nodes. Furthermore, we provide a dynamic look at immunological kinapses and
      synapses in lymph nodes and suggest the existence of distinct patterns of LAT
      redistribution during antigen recognition.

PMID- 20133677
TI  - N-acetylserotonin activates TrkB receptor in a circadian rhythm.
AB  - Brain-derived neurotrophic factor (BDNF) is a cognate ligand for the TrkB
      receptor. BDNF and serotonin often function in a cooperative manner to regulate
      neuronal plasticity, neurogenesis, and neuronal survival. Here we show that NAS
      (N-acetylserotonin) swiftly activates TrkB in a circadian manner and exhibits
      antidepressant effect in a TrkB-dependent manner. NAS, a precursor of melatonin,
      is acetylated from serotonin by AANAT (arylalkylamine N-acetyltransferase). NAS
      rapidly activates TrkB, but not TrkA or TrkC, in a neurotrophin- and MT3 receptor
      independent manner. Administration of NAS activates TrkB in BDNF knockout mice.
      Furthermore, NAS, but not melatonin, displays a robust antidepressant-like
      behavioral effect in a TrkB-dependent way. Endogenous TrkB is activated in wild
      type C3H/f(+/+) mice but not in AANAT-mutated C57BL/6J mice, in a circadian
      rhythm; TrkB activation is high at night in the dark and low during the day.
      Hence, our findings support that NAS is more than a melatonin precursor, and that
      it can potently activate TrkB receptor.

PMID- 20133678
TI  - Nature's molecular sponges: small heat shock proteins grow into their chaperone
      roles.

PMID- 20133679
TI  - Representational gain in cortical area underlies increase of memory strength.
AB  - Neuronal plasticity that develops in the cortex during learning is assumed to
      represent memory content, but the functions of such plasticity are actually
      unknown. The shift in spectral tuning in primary auditory cortex (A1) to the
      frequency of a tone signal is a compelling candidate for a substrate of memory
      because it has all of the cardinal attributes of associative memory:
      associativity, specificity, rapid induction, consolidation, and long-term
      retention. Tuning shifts increase the representational area of the signal in A1,
      as an increasing function of performance level, suggesting that area encodes the
      magnitude of acquired stimulus significance. The present study addresses the
      question of the specific function of learning-induced associative
      representational plasticity. We tested the hypothesis that specific increases in
      A1 representational area for an auditory signal serve the mnemonic function of
      enhancing memory strength for that signal. Rats were trained to bar-press for
      reward contingent on the presence of a signal tone (5.0 kHz), and assessed for
      memory strength during extinction. The amount of representational area gain for
      the signal frequency band was significantly positively correlated with resistance
      to extinction to the signal frequency in two studies that spanned the range of
      task difficulty. These findings indicate that specific gain in cortical
      representational area underlies the strength of the behaviorally-relevant
      contents of memory. Thus, mnemonic functions of cortical plasticity are
      determinable.

PMID- 20133680
TI  - Dynamic regulation of functionally distinct virus-specific T cells.
AB  - The functional capacities of CD8(+) T cells important for virus clearance are
      influenced by interactions with antigen presenting cells (APCs) and CD4(+) T
      cells during initial selection, subsequent expansion, and development of memory.
      Recently, investigators have shown that polyfunctional T cells correlate best
      with long-term protection, however, it is still unknown how to stimulate T cells
      to achieve these responses. To study this, we examined the phenotypes and
      functions of CD8(+) T cells specific for two different virus antigens stimulated
      ex vivo using either autologous monocyte-derived dendritic cells (moDCs) or HLA
      A2-Ig-based artificial APCs (aAPCs). Although similar numbers of influenza virus
      and measles virus tetramer-positive cells were generated by stimulation with
      peptide-loaded moDCs and aAPCs, T cell function, assessed by expression of IL-2,
      IFN-gamma, TNF-alpha, MIP1beta, and CD107a, showed that aAPC-generated CD8(+) T
      cells were multifunctional, whereas moDC-generated cells were mostly
      monofunctional. aAPC-generated cells also produced more of each cytokine per cell
      than CD8(+) T cells generated with moDCs. These phenotypes were not fixed, as
      changing the culture conditions of expanding T cells from aAPCs to moDCs, and
      moDCs to aAPCs, reversed the phenotypes. We conclude that CD8(+) T cells are
      heterogeneous in their functionality and that this is dependent, in a dynamic
      way, on the stimulating APC. These studies will lead to understanding the factors
      that influence induction of optimal CD8(+) T cell function.

PMID- 20133681
TI  - Development and application of in vivo molecular traps reveals that dynein light
      chain occupancy differentially affects dynein-mediated processes.
AB  - The ability to rapidly and specifically regulate protein activity combined with
      in vivo functional assays and/or imaging can provide unique insight into
      underlying molecular processes. Here we describe the application of chemically
      induced dimerization of FKBP to create nearly instantaneous high-affinity
      bivalent ligands capable of sequestering cellular targets from their endogenous
      partners. We demonstrate the specificity and efficacy of these inducible, dimeric
      "traps" for the dynein light chains LC8 (Dynll1) and TcTex1 (Dynlt1). Both light
      chains can simultaneously bind at adjacent sites of dynein intermediate chain at
      the base of the dynein motor complex, yet their specific function with respect to
      the dynein motor or other interacting proteins has been difficult to dissect.
      Using these traps in cultured mammalian cells, we observed that induction of
      dimerization of either the LC8 or TcTex1 trap rapidly disrupted early endosomal
      and lysosomal organization. Dimerization of either trap also disrupted Golgi
      organization, but at a substantially slower rate. Using either trap, the time
      course for disruption of each organelle was similar, suggesting a common
      regulatory mechanism. However, despite the essential role of dynein in cell
      division, neither trap had a discernable effect on mitotic progression. Taken
      together, these studies suggest that LC occupancy of the dynein motor complex
      directly affects some, but not all, dynein-mediated processes. Although the
      described traps offer a method for rapid inhibition of dynein function, the
      design principle can be extended to other molecular complexes for in vivo
      studies.

PMID- 20133682
TI  - Mechanical amplification by hair cells in the semicircular canals.
AB  - Sensory hair cells are the essential mechanotransducers of the inner ear,
      responsible not only for the transduction of sound and motion stimuli but also,
      remarkably, for nanomechanical amplification of sensory stimuli. Here we show
      that semicircular canal hair cells generate a mechanical nonlinearity in vivo
      that increases sensitivity to angular motion by amplification at low stimulus
      strengths. Sensitivity at high stimulus strengths is linear and shows no evidence
      of amplification. Results suggest that the mechanical work done by hair cells
      contributes approximately 97 zJ/cell of amplification per stimulus cycle,
      improving sensitivity to angular velocity stimuli below approximately 5 degrees
      /s (0.3-Hz sinusoidal motion). We further show that mechanical amplification can
      be inhibited by the brain via activation of efferent synaptic contacts on hair
      cells. The experimental model was the oyster toadfish, Opsanus tau. Physiological
      manifestation of mechanical amplification and efferent control in a teleost
      vestibular organ suggests the active motor process in sensory hair cells is
      ancestral. The biophysical basis of the motor(s) remains hypothetical, but a key
      discriminating question may involve how changes in somatic electrical impedance
      evoked by efferent synaptic action alter function of the motor(s).

PMID- 20133683
TI  - Capillarity theory for the fly-casting mechanism.
AB  - Biomolecular folding and function are often coupled. During molecular recognition
      events, one of the binding partners may transiently or partially unfold, allowing
      more rapid access to a binding site. We describe a simple model for this fly
      casting mechanism based on the capillarity approximation and polymer chain
      statistics. The model shows that fly casting is most effective when the protein
      unfolding barrier is small and the part of the chain which extends toward the
      target is relatively rigid. These features are often seen in known examples of
      fly casting in protein-DNA binding. Simulations of protein-DNA binding based on
      well-funneled native-topology models with electrostatic forces confirm the trends
      of the analytical theory.

PMID- 20133684
TI  - Sex determines the expression level of one third of the actively expressed genes
      in bovine blastocysts.
AB  - Although genetically identical for autosomal Chrs (Chr), male and female
      preimplantation embryos could display sex-specific transcriptional regulation. To
      illustrate sex-specific differences at the mRNA level, we compared gene
      expression patterns between male and female blastocysts by DNA microarray
      comparison of nine groups of 60 bovine in vitro-produced blastocysts of each sex.
      Almost one-third of the transcripts detected showed sexual dimorphism (2,921
      transcripts; false-discovery rate, P < 0.05), suggesting that in the absence of
      hormonal influences, the sex Chrs impose an extensive transcriptional regulation
      upon autosomal genes. Six genes were analyzed by qPCR in in vivo-derived embryos,
      which displayed similar sexual dimorphism. Ontology analysis suggested a higher
      global transcriptional level in females and a more active protein metabolism in
      males. A gene homolog to an X-linked gene involved in network interactions during
      spliceosome assembly was found in the Y-Chr. Most of the X-linked-expressed
      transcripts (88.5%) were up-regulated in females, but most of them (70%)
      exhibited fold-changes lower than 1.6, suggesting that X-Chr inactivation is
      partially achieved at the blastocyst stage. Almost half of the transcripts up
      regulated in female embryos exhibiting more than 1.6-fold change were present in
      the X-Chr and eight of them were selected to determine a putative paternal
      imprinting by gene expression comparison with parthenogenetic embryos. Five (BEX,
      CAPN6, BEX2, SRPX2, and UBE2A) exhibited a higher expression in females than in
      parthenotes, suggesting that they are predominantly expressed by the paternal
      inherited X-Chr and that imprinting may increase the transcriptional skew caused
      by double X-Chr dosage.

PMID- 20133685
TI  - Structural basis for inhibition of complement C5 by the SSL7 protein from
      Staphylococcus aureus.
AB  - Staphylococcus aureus secretes the SSL7 protein as part of its immune evasion
      strategy. The protein binds both complement C5 and IgA, yet it is unclear whether
      SSL7 cross-links these two proteins and, if so, what purpose this serves the
      pathogen. We have isolated a stable IgA-SSL7-C5 complex, and our crystal
      structure of the C5-SSL7 complex confirms that binding to C5 occurs exclusively
      through the C-terminal beta-grasp domain of SSL7 leaving the OB domain free to
      interact with IgA. SSL7 interacts with C5 >70 A from the C5a cleavage site
      without inducing significant conformational changes in C5, and efficient
      inhibition of convertase cleavage of C5 is shown to be IgA dependent. Inhibition
      of C5a production and bacteriolysis are all shown to require C5 and IgA binding
      while inhibition of hemolysis is achieved by the C5 binding SSL7 beta-grasp
      domain alone. These results provide a conceptual and structural basis for the
      development of a highly specific complement inhibitor preventing only the
      formation of the lytic membrane attack complex without affecting the important
      signaling functions of C5a.

PMID- 20133686
TI  - Argonautes ALG-3 and ALG-4 are required for spermatogenesis-specific 26G-RNAs and
      thermotolerant sperm in Caenorhabditis elegans.
AB  - Gametogenesis is a thermosensitive process in numerous metazoans, ranging from
      worms to man. In Caenorhabditis elegans, a variety of RNA-binding proteins that
      associate with germ-line nuage (P granules), including the Piwi-clade argonaute
      PRG-1, have been implicated in maintaining fertility at elevated temperature.
      Here we describe the role of two AGO-class paralogs, alg-3 (T22B3.2) and alg-4
      (ZK757.3), in promoting thermotolerant male fertility. A rescuing GFP::alg-3
      transgene is localized to P granules beginning at the late pachytene stage of
      male gametogenesis. alg-3/4 double mutants lack a subgroup of small RNAs, the 26G
      RNAs which target and appear to down-regulate numerous spermatogenesis-expressed
      mRNAs. These findings add to a growing number of AGO pathways required for
      thermotolerant fertility in C. elegans and support a model in which AGOs and
      their small RNA cofactors function to promote robustness in gene-expression
      networks.

PMID- 20133687
TI  - Synergistic roles of the proteasome and autophagy for mitochondrial maintenance
      and chronological lifespan in fission yeast.
AB  - Regulations of proliferation and quiescence in response to nutritional cues are
      important for medicine and basic biology. The fission yeast Schizosaccharomyces
      pombe serves as a model, owing to the shift of proliferating cells to the
      metabolically active quiescence (designate G0 phase hereafter) by responding to
      low nitrogen source. S. pombe G0 phase cells keep alive for months without growth
      and division. Nitrogen replenishment reinstates vegetative proliferation phase
      (designate VEG). Some 40 genes required for G0 maintenance were identified, but
      many more remain to be identified. We here show, using mutants, that the
      proteasome is required for maintaining G0 quiescence. Functional outcomes of
      proteasome in G0 and VEG phases appear to be distinct. Upon proteasome
      dysfunction, a number of antioxidant proteins and compounds responsive to ROS
      (reactive oxygen species) are produced. In addition, autophagy-mediated
      destruction of mitochondria occurs, which suppresses the loss of viability by
      eliminating ROS-generating mitochondria. These defensive responses are found in
      G0 but not in VEG, suggesting that the main function of proteasome in G0 phase
      homeostasis is to minimize ROS. Proteasome and autophagy are thus collaborative
      to support the lifespan of S. pombe G0 phase.

PMID- 20133688
TI  - NIP45 controls the magnitude of the type 2 T helper cell response.
AB  - Nuclear factor of activated T cell (NFAT) transcription factors are key
      regulators of gene transcription within immune cells. The NFAT-interacting
      protein, (NIP45), augments NFAT-driven IL-4 expression by a mechanism that relies
      on arginine methylation. To establish the function of NIP45 in vivo, we generated
      mice with a targeted deletion of the gene encoding this cofactor. NIP45-deficient
      T helper cells displayed profound defects in the expression of NFAT-regulated
      cytokine genes, including IL-4. Whereas NIP45 deficiency does not interfere with
      T helper cell NFAT activation or lineage-specific transcription-factor
      expression, NIP45 acts as an enhancer for the assembly of protein arginine
      methyltransferase 1 and the protein arginine methyltransferase 1-linked histone 4
      arginine 3 methylation with the IL-4 promoter. Our study reveals an essential
      role for NIP45 in promoting robust cytokine expression in vivo, which is required
      for the efficient handling of parasites. We propose that NIP45 acts as a
      molecular rheostat serving to amplify the type-2 immune response.

PMID- 20133689
TI  - Minimalist design of water-soluble cross-beta architecture.
AB  - Demonstrated successes of protein design and engineering suggest significant
      potential to produce diverse protein architectures and assemblies beyond those
      found in nature. Here, we describe a new class of synthetic protein architecture
      through the successful design and atomic structures of water-soluble cross-beta
      proteins. The cross-beta motif is formed from the lamination of successive beta
      sheet layers, and it is abundantly observed in the core of insoluble amyloid
      fibrils associated with protein-misfolding diseases. Despite its prominence,
      cross-beta has been designed only in the context of insoluble aggregates of
      peptides or proteins. Cross-beta's recalcitrance to protein engineering and
      conspicuous absence among the known atomic structures of natural proteins thus
      makes it a challenging target for design in a water-soluble form. Through
      comparative analysis of the cross-beta structures of fibril-forming peptides, we
      identified rows of hydrophobic residues ("ladders") running across beta-strands
      of each beta-sheet layer as a minimal component of the cross-beta motif. Grafting
      a single ladder of hydrophobic residues designed from the Alzheimer's amyloid
      beta peptide onto a large beta-sheet protein formed a dimeric protein with a
      cross-beta architecture that remained water-soluble, as revealed by solution
      analysis and x-ray crystal structures. These results demonstrate that the cross
      beta motif is a stable architecture in water-soluble polypeptides and can be
      readily designed. Our results provide a new route for accessing the cross-beta
      structure and expanding the scope of protein design.

PMID- 20133690
TI  - Autologous engineering of cartilage.
AB  - Treatment of full-thickness damage to hyaline cartilage is hampered by the
      limited availability of autologous healthy cartilage and the lengthy, cost
      prohibitive cell isolation and expansion steps associated with autologous
      cartilage implantation (ACI). Here we report a strategy for de novo engineering
      of ectopic autologous cartilage (EAC) within the subperiosteal space (in vivo
      bioreactor), through the mere introduction of a biocompatible gel that might
      promote hypoxia-mediated chondrogenesis, thereby effectively overcoming the
      aforementioned limitations. The EAC is obtained within 3 wk post injection of the
      gel, and can be press-fit into an osteochondral defect where it undergoes
      remodeling with good lateral and subchondral integration. The implanted EAC
      showed no calcification even after 9 mo and attained an average O'Driscoll score
      of 11 (versus 4 for controls). An "on demand" autologous source of autologous
      cartilage with remodeling capacity is expected to significantly impact the
      clinical options in repair of trauma to articular cartilage.

PMID- 20133691
TI  - Computation of symmetric, time-periodic solutions of the vortex sheet with
      surface tension.
AB  - A numerical method is introduced for the computation of time-periodic vortex
      sheets with surface tension separating two immiscible, irrotational, two
      dimensional ideal fluids of equal density. The approach is based on minimizing a
      nonlinear functional of the initial conditions and supposed period that is
      positive unless the solution is periodic, in which case it is zero. An adjoint
      based optimal control technique is used to efficiently compute the gradient of
      this functional. Special care is required to handle singular integrals in the
      adjoint formulation. Starting with a solution of the linearized problem about the
      flat rest state, a family of smooth, symmetric breathers is found that, at
      quarter-period time intervals, alternately pass through a flat state of maximal
      kinetic energy, and a rest state in which all the energy is stored as potential
      energy in the interface. In some cases, the interface overturns before returning
      to the initial, flat configuration. It is found that the bifurcation diagram
      describing these solutions contains several disjoint curves separated by near
      bifurcation events.

PMID- 20133692
TI  - Role of the histone domain in the autoinhibition and activation of the Ras
      activator Son of Sevenless.
AB  - Membrane-bound Ras is activated by translocation of the Son of Sevenless (SOS)
      protein to the plasma membrane. SOS is inactive unless Ras is bound to an
      allosteric site on SOS, and the Dbl homology (DH) and Pleckstrin homology (PH)
      domains of SOS (the DH-PH unit) block allosteric Ras binding. We showed
      previously that the activity of SOS at the membrane increases with the density of
      PIP(2) and the local concentration of Ras-GTP, which synergize to release the DH
      PH unit. Here we present a new crystal structure of SOS that contains the N
      terminal histone domain in addition to the DH-PH unit and the catalytic unit
      (SOS(HDFC), residues 1-1049). The structure reveals that the histone domain plays
      a dual role in occluding the allosteric site and in stabilizing the
      autoinhibitory conformation of the DH-PH unit. Additional insight is provided by
      kinetic analysis of the activation of membrane-bound Ras by mutant forms of SOS
      that contain mutations in the histone and the PH domains (E108K, C441Y, and
      E433K) that are associated with Noonan syndrome, a disease caused by hyperactive
      Ras signaling. Our results indicate that the histone domain and the DH-PH unit
      are conformationally coupled, and that the simultaneous engagement of the
      membrane by a PH domain PIP(2)-binding interaction and electrostatic interactions
      between a conserved positively charged patch on the histone domain and the
      negatively charged membrane coincides with a productive reorientation of SOS at
      the membrane and increased accessibility of both Ras binding sites on SOS.

PMID- 20133693
TI  - Reactive and nonreactive quenching of O(1D) by the potent greenhouse gases SO2F2,
      NF3, and SF5CF3.
AB  - A laser flash photolysis-resonance fluorescence technique has been employed to
      measure rate coefficients and physical vs. reactive quenching branching ratios
      for O((1)D) deactivation by three potent greenhouse gases, SO(2)F(2)(k(1)),
      NF(3)(k(2)), and SF(5)CF(3)(k(3)). In excellent agreement with one published
      study, we find that k(1)(T) = 9.0 x 10(-11) exp(+98/T) cm(3) molecule(-1) s(-1)
      and that the reactive quenching rate coefficient is k(1b) = (5.8 +/- 2.3) x 10(
      11) cm(3) molecule(-1) s(-1) independent of temperature. We find that k(2)(T) =
      2.0 x 10(-11) exp(+52/T) cm(3) molecule(-1) s(-1) with reaction proceeding almost
      entirely (approximately 99%) by reactive quenching. Reactive quenching of O((1)D)
      by NF(3) is more than a factor of two faster than reported in one published
      study, a result that will significantly lower the model-derived atmospheric
      lifetime and global warming potential of NF(3). Deactivation of O((1)D) by
      SF(5)CF(3) is slow enough (k(3) < 2.0 x 10(-13) cm(3) molecule(-1) s(-1) at 298
      K) that reaction with O((1)D) is unimportant as an atmospheric removal mechanism
      for SF(5)CF(3). The kinetics of O((1)D) reactions with SO(2) (k(4)) and CS(2)
      (k(5)) have also been investigated at 298 K. We find that k(4) = (2.2 +/- 0.3) x
      10(-10) and k(5) = (4.6 +/- 0.6) x 10(-10) cm(3) molecule(-1) s(-1); branching
      ratios for reactive quenching are 0.76 +/- 0.12 and 0.94 +/- 0.06 for the SO(2)
      and CS(2) reactions, respectively. All uncertainties reported above are estimates
      of accuracy (2sigma) and rate coefficients k(i)(T) (i = 1,2) calculated from the
      above Arrhenius expressions have estimated accuracies of +/- 15% (2sigma).

PMID- 20133694
TI  - Allosteric gating of Son of sevenless activity by the histone domain.
AB  - Regulated activation of Ras by receptor tyrosine kinases (RTK) constitutes a key
      transduction step in signaling processes that control an array of fundamental
      cellular functions including proliferation, differentiation, and survival. The
      principle mechanism by which Ras is activated down stream of RTKs involves the
      stimulation of guanine nucleotide exchange by the ubiquitous guanine nucleotide
      exchange factor Son of sevenless (Sos). In resting conditions, Sos activity is
      constrained by intramolecular interactions that maintain the protein in an
      autoinhibited conformation. Structural, biochemical, and genetic studies have
      implicated the histone domain (Sos-H), which comprises the most N-terminal region
      of Sos, in the regulation of Sos autoinhibition. However, the molecular
      underpinnings of this regulatory function are not well understood. In the present
      study we demonstrate that Sos-H possesses in vitro and in vivo membrane binding
      activity that is mediated, in part, by the interactions between a cluster of
      basic residues and phosphatidic acid. This interaction is required for Sos
      dependent activation of Ras following EGF stimulation. The inducible association
      of Sos-H with membranes contributes to the catalytic activity of Sos by forcing
      the domain to adopt a conformation that destabilizes the autoinhibitory state.
      Thus, Sos-H plays a critical role in governing the catalytic output of Sos
      through the coupling of membrane recruitment to the release of autoinhibition.

PMID- 20133695
TI  - DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of
      the AKT pathway.
AB  - Loss-of-function DJ-1 (PARK7) mutations have been linked with a familial form of
      early onset Parkinson disease. Numerous studies have supported the role of DJ-1
      in neuronal survival and function. Our initial studies using DJ-1-deficient
      neurons indicated that DJ-1 specifically protects the neurons against the damage
      induced by oxidative injury in multiple neuronal types and degenerative
      experimental paradigms, both in vitro and in vivo. However, the manner by which
      oxidative stress-induced death is ameliorated by DJ-1 is not completely clear. We
      now present data that show the involvement of DJ-1 in modulation of AKT, a major
      neuronal prosurvival pathway induced upon oxidative stress. We provide evidence
      that DJ-1 promotes AKT phosphorylation in response to oxidative stress induced by
      H(2)O(2) in vitro and in vivo following 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) treatment. Moreover, we show that DJ-1 is necessary for
      normal AKT-mediated protective effects, which can be bypassed by expression of a
      constitutively active form of AKT. Taken together, these data suggest that DJ-1
      is crucial for full activation of AKT upon oxidative injury, which serves as one
      explanation for the protective effects of DJ-1.

PMID- 20133696
TI  - Reactive oxygen species-independent activation of the IL-1beta inflammasome in
      cells from patients with chronic granulomatous disease.
AB  - Humans with chronic granulomatous diseases (CGDs) due to mutations in p47-phox
      have defective NADPH activity and thus cannot generate NADPH-dependent reactive
      oxygen species (ROS). The role of ROS in inflammation is controversial; some in
      vitro studies suggest that ROS are crucial for secretion of IL-1beta via
      inflammasome activation, whereas mice defective for ROS and patients with CGD
      have a proinflammatory phenotype. In this study, we evaluated activation of the
      IL-1beta inflammasome in cells from CGD patients. In contrast to previous studies
      using the small molecule diphenylene iodonium (DPI) as a ROS inhibitor, we found
      no decrease in either caspase-1 activation or secretion of IL-1beta and IL-18 in
      primary CGD monocytes. Moreover, activation of CGD monocytes by uric acid
      crystals induced a 4-fold higher level of IL-1beta secretion compared with that
      seen in monocytes from unaffected subjects, and this increase was not due to
      increased synthesis of the IL-1beta precursor. In addition, Western blot analysis
      of CGD cells revealed that caspase-1 activation was not decreased, but rather was
      increased compared with control cells. Examination of the effects exerted by the
      inhibition of ROS activity by DPI revealed that the decrease in IL-1beta
      secretion by DPI was actually due to inhibition of IL-1beta gene expression.
      Thus, inconsistent with the proinflammatory role of ROS, the present findings
      support the concept that ROS likely dampen inflammasome activation. The absence
      of ROS in CGD monocytes may explain the presence of an inflammatory phenotype
      characterized by granulomas and inflammatory bowel disease occurring in CGD
      patients.

PMID- 20133697
TI  - Expression of cancer testis antigen CT45 in classical Hodgkin lymphoma and other
      B-cell lymphomas.
AB  - We have shown previously that cancer/testis (CT) antigen, CT45, is expressed in
      various epithelial cancers at a frequency of <5% to approximately 35%. In this
      study, the protein expression of CT45 was examined in non-Hodgkin B-cell
      lymphomas and classical Hodgkin lymphoma by immunohistochemical analysis.
      Serological response to CT45 was also evaluated by ELISA using CT45 recombinant
      protein and sera from patients with Hodgkin lymphoma. None of the 80 low-grade B
      cell lymphomas, including chronic lymphocytic leukemia/small lymphocytic
      lymphoma, follicular lymphoma, and mantle cell lymphoma, expressed CT45. In
      comparison, CT45 was expressed in 28 of 126 (22%) diffuse large B-cell lymphomas
      (DLBCL). A remarkably high percentage (42/72, 58%) of classical Hodgkin lymphoma
      contained CT45-positive Reed-Sternberg cells. Nodular sclerosis and mixed
      cellularity subtypes had similar frequency of CT45 expression, but most EBV
      positive cases were CT45 negative. Gray-zone lymphoma (cases with features of
      both DLBCL and classical Hodgkin lymphoma) also showed frequent (64%) CT45
      expression. Evaluation of reactive lymphoid tissues showed scattered CT45
      positive lymphocytes in a single case of florid follicular hyperplasia, raising
      the possibility that this case was an evolving malignancy. Despite frequent CT45
      expression, only 1 of 67 Hodgkin lymphoma patients had detectable anti-CT45
      antibodies in the serum, suggesting that the immune response to CT45 may be
      suppressed. In conclusion, classical Hodgkin lymphoma has the highest frequency
      of CT45 expression among all malignancies tested to date, the frequency of CT45
      expression in DLBCL is similar to that seen in epithelial cancers, and low-grade
      non-Hodgkin B-cell lymphomas do not express CT45.

PMID- 20133698
TI  - Arabidopsis V-ATPase activity at the tonoplast is required for efficient nutrient
      storage but not for sodium accumulation.
AB  - The productivity of higher plants as a major source of food and energy is linked
      to their ability to buffer changes in the concentrations of essential and toxic
      ions. Transport across the tonoplast is energized by two proton pumps, the
      vacuolar H(+)-ATPase (V-ATPase) and the vacuolar H(+)-pyrophosphatase (V-PPase);
      however, their functional relation and relative contributions to ion storage and
      detoxification are unclear. We have identified an Arabidopsis mutant in which
      energization of vacuolar transport solely relies on the activity of the V-PPase.
      The vha-a2 vha-a3 double mutant, which lacks the two tonoplast-localized isoforms
      of the membrane-integral V-ATPase subunit VHA-a, is viable but shows day-length
      dependent growth retardation. Nitrate content is reduced whereas nitrate
      assimilation is increased in the vha-a2 vha-a3 mutant, indicating that vacuolar
      nitrate storage represents a major growth-limiting factor. Zinc is an essential
      micronutrient that is toxic at excess concentrations and is detoxified via a
      vacuolar Zn(2+)/H(+)-antiport system. Accordingly, the double mutant shows
      reduced zinc tolerance. In the same way the vacuolar Na(+)/H(+)-antiport system
      is assumed to be an important component of the system that removes sodium from
      the cytosol. Unexpectedly, salt tolerance and accumulation are not affected in
      the vha-a2 vha-a3 double mutant. In contrast, reduction of V-ATPase activity in
      the trans-Golgi network/early endosome (TGN/EE) leads to increased salt
      sensitivity. Taken together, our results show that during gametophyte and embryo
      development V-PPase activity at the tonoplast is sufficient whereas tonoplast V
      ATPase activity is limiting for nutrient storage but not for sodium tolerance
      during vegetative and reproductive growth.

PMID- 20133699
TI  - Long-range enhancers on 8q24 regulate c-Myc.
AB  - Recent genomewide association studies have found multiple genetic variants on
      chromosome 8q24 that are significantly associated with an increased
      susceptibility to prostate, colorectal, and breast cancer. These risk loci are
      located in a "gene desert," a few hundred kilobases telomeric to the Myc gene. To
      date, the biological mechanism(s) underlying these associations remain unclear.
      It has been speculated that these 8q24 genetic variant(s) might affect Myc
      expression by altering its regulation or amplification status. Here, we show that
      multiple enhancer elements are present within this region and that they can
      regulate transcription of Myc. We also demonstrate that one such enhancer element
      physically interacts with the Myc promoter via transcription factor Tcf-4 binding
      and acts in an allele specific manner to regulate Myc expression.

PMID- 20133700
TI  - IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses
      following acute viral infection.
AB  - Mounting effective T cell responses is critical for eliciting long-lasting
      immunity following viral infection and vaccination. A multitude of inhibitory and
      stimulatory factors are induced following infection, and it is the compilation of
      these signals that quantitatively and qualitatively program the ensuing effector
      and memory T cell response. In response to lymphocytic choriomeningitis virus
      (LCMV) infection, the immunosuppressive cytokine IL-10 is rapidly up-regulated;
      however, how IL-10 is regulating what is often considered an "optimal" immune
      response is unclear. We demonstrate that IL-10 directly inhibits effector and
      memory CD4 T cell responses following an acutely resolved viral infection.
      Blockade of IL-10 enhanced the magnitude and the functional capacity of effector
      CD4 T cells that translated into increased and more effective memory responses.
      On the other hand, lack of IL-10 signaling did not impact memory CD8 T cell
      development. We propose that blockade of IL-10 may be an effective adjuvant to
      specifically enhance CD4 T cell immunity and protection following vaccination.

PMID- 20133701
TI  - LIM protein Ajuba functions as a nuclear receptor corepressor and negatively
      regulates retinoic acid signaling.
AB  - Corepressors play an essential role in nuclear receptor-mediated transcriptional
      repression. In general, corepressors directly bind to nuclear receptors via CoRNR
      boxes (L/I-X-X-I/V-I) in the absence of ligand and appear to act as scaffolds to
      further recruit chromatin remodeling complexes to specific target genes. Here, we
      describe the identification of the multiple LIM domain protein Ajuba as a unique
      corepressor for a subset of nuclear hormone receptors. Ajuba contains functional
      nuclear-receptor interacting motifs and selectively interacts with retinoic acid
      receptors (RARs) and rexinoid receptor (RXRs) subtypes in a ligand-dependent
      manner. Simultaneous mutation of these motifs abolishes RAR binding and
      concomitantly leads to loss of repression on RARE reporter genes. P19 cells
      depleted of Ajuba are highly sensitized to all-trans retinoic acid (atRA)-induced
      transcription and differentiation. In the absence of atRA, Ajuba can be readily
      found at the RARE control elements of RAR endogenous target genes. Stimulation of
      cells with atRA results in the dissociation of Ajuba from these regions.
      Moreover, we observed that coexpression of the known Ajuba binding partner Prmt5
      (protein arginine methyltransferase-5) inhibited the Ajuba/RAR interaction. The
      high-affinity Ajuba-RAR/RXR interaction site overlaps the region responsible for
      Ajuba/Prmt5 binding, and thus binding appears to be mutually exclusive, providing
      a potential mechanism for these observations. Identification of Ajuba as a unique
      corepressor for nuclear receptors sheds new light on mechanisms for nuclear
      receptor-mediated repression and provides a unique target for developing more
      effective therapeutics to modulate this important pathway.

PMID- 20133702
TI  - Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity.
AB  - Under fasting conditions, increases in circulating concentrations of pancreatic
      glucagon maintain glucose homeostasis through induction of gluconeogenic genes by
      the CREB coactivator CRTC2. Hepatic CRTC2 activity is elevated in obesity,
      although the extent to which this cofactor contributes to attendant increases in
      insulin resistance is unclear. Here we show that mice with a knockout of the
      CRTC2 gene have decreased circulating glucose concentrations during fasting, due
      to attenuation of the gluconeogenic program. CRTC2 was found to stimulate hepatic
      gene expression in part through an N-terminal CREB binding domain that enhanced
      CREB occupancy over relevant promoters in response to glucagon. Deletion of
      sequences encoding the CREB binding domain in CRTC2 (-/-) mice lowered
      circulating blood glucose concentrations and improved insulin sensitivity in the
      context of diet-induced obesity. Our results suggest that small molecules that
      attenuate the CREB-CRTC2 pathway may provide therapeutic benefit to individuals
      with type 2 diabetes.

PMID- 20133703
TI  - Proliferative lesions and metalloproteinase activity in murine lupus nephritis
      mediated by type I interferons and macrophages.
AB  - Glomerulonephritis is a major cause of morbidity in patients with systemic lupus
      erythematosus. Although substantial progress has been made in the identification
      of pathogenic triggers that result in autoantibody production, little is known
      about the pathogenesis of aggressive proliferative processes that lead directly
      to irreversible glomerular damage and compromise of renal function. In this
      study, we describe a model of polyinosinic: polycytidylic acid-accelerated lupus
      nephritis in NZB/W mice that is characterized by severe glomerular proliferative
      lesions with de novo crescent formation, findings that are linked with decreased
      survival and adverse outcomes in lupus. Proliferative glomerulonephritis was
      associated with infiltrating kidney macrophages and renal expression of IFN
      inducible genes, matrix metalloproteinases (MMPs), and growth factors. Crescent
      formation and renal MMP and growth factor expression were dependent on renal
      macrophages that expressed Il10, MMPs, osteopontin, and growth factors, including
      Pdgfc and Hbegf. Infiltrating macrophages and renal MMP expression were induced
      by type I IFN. These findings reveal a role for type I IFNs and alternatively
      activated macrophages in aggressive proliferative lesions of lupus nephritis.

PMID- 20133704
TI  - Enhancement of GABA(A)-current run-down in the hippocampus occurs at the first
      spontaneous seizure in a model of temporal lobe epilepsy.
AB  - Refractory temporal lobe epilepsy (TLE) is associated with a dysfunction of
      inhibitory signaling mediated by GABA(A) receptors. In particular, the use
      dependent decrease (run-down) of the currents (I(GABA)) evoked by the repetitive
      activation of GABA(A) receptors is markedly enhanced in hippocampal and cortical
      neurons of TLE patients. Understanding the role of I(GABA) run-down in the
      disease, and its mechanisms, may allow development of medical alternatives to
      surgical resection, but such mechanistic insights are difficult to pursue in
      surgical human tissue. Therefore, we have used an animal model (pilocarpine
      treated rats) to identify when and where the increase in I(GABA) run-down occurs
      in the natural history of epilepsy. We found: (i) that the increased run-down
      occurs in the hippocampus at the time of the first spontaneous seizure (i.e.,
      when the diagnosis of epilepsy is made), and then extends to the neocortex and
      remains constant in the course of the disease; (ii) that the phenomenon is
      strictly correlated with the occurrence of spontaneous seizures, because it is
      not observed in animals that do not become epileptic. Furthermore, initial
      exploration of the molecular mechanism disclosed a relative increase in alpha4-,
      relative to alpha1-containing GABA(A) receptors, occurring at the same time when
      the increased run-down appears, suggesting that alterations in the molecular
      composition of the GABA receptors may be responsible for the occurrence of the
      increased run-down. These observations disclose research opportunities in the
      field of epileptogenesis that may lead to a better understanding of the mechanism
      whereby a previously normal tissue becomes epileptic.

PMID- 20133705
TI  - PML/RARalpha fusion protein transactivates the tissue factor promoter through a
      GAGC-containing element without direct DNA association.
AB  - A severe coagulopathy is a life-threatening complication of acute promyelocytic
      leukemia (APL) and is ascribable mainly to the excessive levels of tissue factor
      (TF) in APL cells regulated in response to the promyelocytic leukemia/retinoic
      acid receptor alpha (PML/RARalpha) fusion protein. The underlying molecular
      mechanisms for this regulation remain ill-defined. With U937-PR9 cell lines
      stably expressing luciferase reporter gene under the control of different mutants
      of the TF promoter, both luciferase and ChIP data allowed the localization of the
      PML/RARalpha-responsive sequence in a previously undefined region of the TF
      promoter at position -230 to -242 devoid of known mammalian transcription factor
      binding sites. Within this sequence a GAGC motif (-235 to -238) was shown to be
      crucial because deletion or mutation of these nucleotides impaired both
      PML/RARalpha interaction and promoter transactivation. However, EMSA results
      showed that PML/RARalpha did not bind to DNA probes encompassing the -230 to -242
      sequences, precluding a direct DNA association. Mutational experiments further
      suggest that the activator protein 1 (AP-1) sites of the TF promoter are
      dispensable for PML/RARalpha regulation. This study shows that PML/RARalpha
      transactivates the TF promoter through an indirect interaction with an element
      composed of a GAGC motif and the flanking nucleotides, independent of AP-1
      binding.

PMID- 20133706
TI  - COUP-TFII regulates tumor growth and metastasis by modulating tumor angiogenesis.
AB  - Tumor growth depends on nutrients and oxygen supplied by the vasculature through
      angiogenesis. Here, we show that the chicken ovalbumin upstream promoter
      transcription factor II (COUP-TFII), a member of the nuclear receptor family, is
      a major angiogenesis regulator within the tumor microenvironment. Conditional
      ablation of COUP-TFII in adults severely compromised neoangiogenesis and
      suppressed tumor growth in xenograft mouse models. In addition, tumor growth and
      tumor metastasis were also impaired in a spontaneous mammary-gland tumor model in
      the absence of COUP-TFII. We showed that COUP-TFII directly regulates the
      transcription of Angiopoietin-1 in pericytes to enhance neoangiogenesis.
      Importantly, provision of Angiopoietin-1 partially restores the angiogenic
      defects exhibited by the COUP-TFII-deficient mice, which supports the notion that
      COUP-TFII controls Angiopoietin-1/Tie2 signaling to regulate tumor angiogenesis.
      Because COUP-TFII has little impact on normal adult physiological function, our
      results raise an interesting possibility that inhibition of COUP-TFII may offer a
      therapeutic approach for anticancer intervention.

PMID- 20133707
TI  - Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells
      following ErbB2 activation.
AB  - p53, apoptosis, and senescence are frequently activated in preneoplastic lesions
      and are barriers to progression to malignancy. These barriers have been suggested
      to result from an ATM-mediated DNA damage response (DDR), which may follow
      oncogene-induced hyperproliferation and ensuing DNA replication stress. To
      elucidate the currently untested role of DDR in breast cancer initiation, we
      examined the effect of oncogene expression in several murine models of breast
      cancer. We did not observe a detectable DDR in early hyperplastic lesions arising
      in transgenic mice expressing several different oncogenes. However, DDR signaling
      was strongly induced in preneoplastic lesions arising from individual mammary
      cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus,
      activation of an oncogene after normal tissue development causes a DDR.
      Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required
      for p53 stabilization, apoptosis, and senescence. In palpable tumors in this
      model, p53 stabilization and apoptosis are lost, but unexpectedly senescence
      remains in many tumor cells. Thus, this murine model fully recapitulates early
      DDR signaling; the eventual suppression of its endpoints in tumorigenesis
      provides compelling evidence that ErbB2-induced aberrant mammary cell
      proliferation leads to an ATM-mediated DDR that activates apoptosis and
      senescence, and at least the former must be overcome to progress to malignancy.
      This in vivo study also uncovers an unexpected effect of ErbB2 activation
      previously known for its prosurvival roles, and suggests that protection of the
      ATM-mediated DDR-p53 signaling pathway may be important in breast cancer
      prevention.

PMID- 20133708
TI  - The role of SAP97 in synaptic glutamate receptor dynamics.
AB  - Proteins of the PSD-95-like membrane-associated guanylate kinase (PSD-MAGUK)
      family are vital for trafficking AMPA receptors (AMPARs) to synapses, a process
      necessary for both basal synaptic transmission and forms of synaptic plasticity.
      Synapse-associated protein 97 (SAP97) exhibits protein interactions, such as
      direct interaction with the GluA1 AMPAR subunit, and subcellular localization
      (synaptic, perisynaptic, and dendritic) unique within this protein family. Due in
      part to the lethality of the germline knockout of SAP97, this protein's role in
      synaptic transmission and plasticity is poorly understood. We found that
      overexpression of SAP97 during early development traffics AMPARs and NMDA
      receptors (NMDARs) to synapses, and that SAP97 rescues the deficits in AMPAR
      currents normally seen in PSD-93/-95 double-knockout neurons. Mature neurons that
      have experienced the overexpression of SAP97 throughout development exhibit
      enhanced AMPAR and NMDAR currents, as well as faster NMDAR current decay
      kinetics. In loss-of-function experiments using conditional SAP97 gene deletion,
      we recorded no deficits in glutamatergic transmission or long-term potentiation.
      These results support the hypothesis that SAP97 is part of the machinery that
      traffics glutamate receptors and compensates for other PSD-MAGUKs in knockout
      mouse models. However, due to functional redundancy, other PSD-MAGUKs can
      presumably compensate when SAP97 is conditionally deleted during development.

PMID- 20133709
TI  - LXR modulation blocks prostaglandin E2 production and matrix degradation in
      cartilage and alleviates pain in a rat osteoarthritis model.
AB  - Osteoarthritis (OA), the most common arthritic condition in humans, is
      characterized by the progressive degeneration of articular cartilage accompanied
      by chronic joint pain. Inflammatory mediators, such as cytokines and
      prostaglandin E(2) (PGE(2)) that are elevated in OA joints, play important roles
      in the progression of cartilage degradation and pain-associated nociceptor
      sensitivity. We have found that the nuclear receptor family transcription factors
      Liver X Receptors (LXRalpha and -beta) are expressed in cartilage, with LXRbeta
      being the predominant isoform. Here we show that genetic disruption of Lxrbeta
      gene expression in mice results in significantly increased proteoglycan
      (aggrecan) degradation and PGE(2) production in articular cartilage treated with
      IL-1beta, indicating a protective role of LXRbeta in cartilage. Using human
      cartilage explants, we found that activation of LXRs by the synthetic ligand
      GW3965 significantly reduced cytokine-induced degradation and loss of aggrecan
      from the tissue. Furthermore, LXR activation dramatically inhibited cytokine
      induced PGE(2) production by human osteoarthritic cartilage as well as by a
      synovial sarcoma cell line. These effects were achieved at least partly by
      repression of the expression of ADAMTS4, a physiological cartilage aggrecanase,
      and of cyclooxygenase-2 and microsomal prostaglandin E synthase-1, key enzymes in
      the PGE(2) synthesis pathway. Consistent with our in vitro observations, oral
      administration of GW3965 potently alleviated joint pain in a rat meniscal tear
      model of osteoarthritis.

PMID- 20133710
TI  - Evidence for a recent increase in forest growth.
AB  - Forests and their soils contain the majority of the earth's terrestrial carbon
      stocks. Changes in patterns of tree growth can have a huge impact on atmospheric
      cycles, biogeochemical cycles, climate change, and biodiversity. Recent studies
      have shown increases in biomass across many forest types. This increase has been
      attributed to climate change. However, without knowing the disturbance history of
      a forest, growth could also be caused by normal recovery from unknown
      disturbances. Using a unique dataset of tree biomass collected over the past 22
      years from 55 temperate forest plots with known land-use histories and stand ages
      ranging from 5 to 250 years, we found that recent biomass accumulation greatly
      exceeded the expected growth caused by natural recovery. We have also collected
      over 100 years of local weather measurements and 17 years of on-site atmospheric
      CO(2) measurements that show consistent increases in line with globally observed
      climate-change patterns. Combined, these observations show that changes in
      temperature and CO(2) that have been observed worldwide can fundamentally alter
      the rate of critical natural processes, which is predicted by biogeochemical
      models. Identifying this rate change is important to research on the current
      state of carbon stocks and the fluxes that influence how carbon moves between
      storage and the atmosphere. These results signal a pressing need to better
      understand the changes in growth rates in forest systems, which influence current
      and future states of the atmosphere and biosphere.

PMID- 20133711
TI  - TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions
      characteristic of ALS and frontotemporal lobar degeneration.
AB  - Neuronal cytoplasmic and intranuclear aggregates of RNA-binding protein TDP-43
      are a hallmark feature of neurodegenerative diseases such as amyotrophic lateral
      sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). ALS and FTLD show a
      considerable clinical and pathological overlap and occur as both familial and
      sporadic forms. Though missense mutations in TDP-43 cause rare forms of familial
      ALS, it is not yet known whether this is due to loss of TDP-43 function or gain
      of aberrant function. Moreover, the role of wild-type (WT) TDP-43, associated
      with the majority of familial and sporadic ALS/FTLD patients, is also currently
      unknown. Generating homozygous and hemizygous WT human TDP-43 transgenic mouse
      lines, we show here a dose-dependent degeneration of cortical and spinal motor
      neurons and development of spastic quadriplegia reminiscent of ALS. A dose
      dependent degeneration of nonmotor cortical and subcortical neurons
      characteristic of FTLD was also observed. Neurons in the affected spinal cord and
      brain regions showed accumulation of TDP-43 nuclear and cytoplasmic aggregates
      that were both ubiquitinated and phosphorylated as observed in ALS/FTLD patients.
      Moreover, the characteristic approximately 25-kDa C-terminal fragments (CTFs)
      were also recovered from nuclear fractions and correlated with disease
      development and progression in WT TDP-43 mice. These findings suggest that
      approximately 25-kDa TDP-43 CTFs are noxious to neurons by a gain of aberrant
      nuclear function.

PMID- 20133712
TI  - Noninvasive diagnosis of seed viability using infrared thermography.
AB  - Recent advances in the noninvasive analyses of plant metabolism include stress
      imaging techniques, mainly developed for vegetative tissues. We explored if
      infrared thermography can be used to predict whether a quiescent seed will
      germinate or die upon water uptake. Thermal profiles of viable, aged, and dead
      Pisum sativum seeds were recorded, and image analysis of 22,000 images per
      individual seed showed that infrared thermography can detect imbibition- and
      germination-associated biophysical and biochemical changes. These "thermal
      fingerprints" vary with viability in this species and in Triticum aestivum and
      Brassica napus seeds. Thermogenesis of the small individual B. napus seeds was at
      the limit of the technology. We developed a computer model of "virtual pea
      seeds," that uses Monte Carlo simulation, based on the heat production of major
      seed storage compounds to unravel physico-chemical processes of thermogenesis.
      The simulation suggests that the cooling that dominates the early thermal
      profiles results from the dissolution of low molecular-weight carbohydrates.
      Moreover, the kinetics of the production of such "cooling" compounds over the
      following 100 h is dependent on seed viability. We also developed a deterministic
      tool that predicts in the first 3 hours of water uptake, when seeds can be
      redried and stored again, whether or not a pea seed will germinate. We believe
      that the early separation of individual, ungerminated seeds (live, aged, or dead)
      before destructive germination assessment creates unique opportunities for
      integrative studies on cell death, differentiation, and development.

PMID- 20133713
TI  - Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective
      immunity in humans.
AB  - GNA2132 is a Neisseria meningitidis antigen of unknown function, discovered by
      reverse vaccinology, which has been shown to induce bactericidal antibodies in
      animal models. Here we show that this antigen induces protective immunity in
      humans and it is recognized by sera of patients after meningococcal disease. The
      protein binds heparin in vitro through an Arg-rich region and this property
      correlates with increased survival of the unencapsulated bacterium in human
      serum. Furthermore, two proteases, the meningococcal NalP and human lactoferrin,
      cleave the protein upstream and downstream from the Arg-rich region,
      respectively. We conclude that GNA2132 is an important protective antigen of N.
      meningitidis and we propose to rename it, Neisserial Heparin Binding Antigen
      (NHBA).

PMID- 20133714
TI  - Human and mouse adipose-derived cells support feeder-independent induction of
      pluripotent stem cells.
AB  - Although adipose tissue is an expandable and readily attainable source of
      proliferating, multipotent stem cells, its potential for use in regenerative
      medicine has not been extensively explored. Here we report that adult human and
      mouse adipose-derived stem cells can be reprogrammed to induced pluripotent stem
      (iPS) cells with substantially higher efficiencies than those reported for human
      and mouse fibroblasts. Unexpectedly, both human and mouse iPS cells can be
      obtained in feeder-free conditions. We discovered that adipose-derived stem cells
      intrinsically express high levels of pluripotency factors such as basic FGF,
      TGFbeta, fibronectin, and vitronectin and can serve as feeders for both
      autologous and heterologous pluripotent cells. These results demonstrate a great
      potential for adipose-derived cells in regenerative therapeutics and as a model
      for studying the molecular mechanisms of feeder-free iPS generation and
      maintenance.

PMID- 20133715
TI  - NudC-like protein 2 regulates the LIS1/dynein pathway by stabilizing LIS1 with
      Hsp90.
AB  - The type I lissencephaly gene product LIS1, a key regulator of cytoplasmic
      dynein, is critical for cell proliferation, survival, and neuronal migration.
      However, little is known about the regulation of LIS1. Here, we identify a
      previously uncharacterized mammalian homolog of Aspergillus NudC, NudCL2 (NudC
      like protein 2), as a regulator of LIS1. NudCL2 is localized to the centrosome in
      interphase, and spindle poles and kinetochores during mitosis, a pattern similar
      to the localization of LIS1 and cytoplasmic dynein. Depletion of NudCL2
      destabilized LIS1 and led to phenotypes resembling those of either dynein or LIS1
      deficiency. NudCL2 complexed with and enhanced the interaction between LIS1 and
      Hsp90. Either disruption of the LIS1-Hsp90 interaction with the C terminus of
      NudCL2 or inhibition of Hsp90 chaperone function by geldanamycin decreased LIS1
      stability. Thus, our results suggest that NudCL2 regulates the LIS1/dynein
      pathway by stabilizing LIS1 with Hsp90 chaperone. This represents a hitherto
      undescribed mechanism of the LIS1/dynein regulation in mammalian cells.

PMID- 20133716
TI  - ATP-independent CFTR channel gating and allosteric modulation by phosphorylation.
AB  - Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) channel, an ATP binding cassette (ABC) transporter.
      CFTR gating is linked to ATP binding and dimerization of its two nucleotide
      binding domains (NBDs). Channel activation also requires phosphorylation of the R
      domain by poorly understood mechanisms. Unlike conventional ligand-gated
      channels, CFTR is an ATPase for which ligand (ATP) release typically involves
      nucleotide hydrolysis. The extent to which CFTR gating conforms to classic
      allosteric schemes of ligand activation is unclear. Here, we describe point
      mutations in the CFTR cytosolic loops that markedly increase ATP-independent
      (constitutive) channel activity. This finding is consistent with an allosteric
      gating mechanism in which ligand shifts the equilibrium between inactive and
      active states but is not essential for channel opening. Constitutive mutations
      mapped to the putative symmetry axis of CFTR based on the crystal structures of
      related ABC transporters, a common theme for activating mutations in ligand-gated
      channels. Furthermore, the ATP sensitivity of channel activation was strongly
      enhanced by these constitutive mutations, as predicted for an allosteric
      mechanism (reciprocity between protein activation and ligand occupancy).
      Introducing constitutive mutations into CFTR channels that cannot open in
      response to ATP (i.e., the G551D CF mutant and an NBD2-deletion mutant)
      substantially rescued their activities. Importantly, constitutive mutants that
      opened without ATP or NBD2 still required R domain phosphorylation for optimal
      activity. Our results confirm that (i) CFTR gating exhibits features of protein
      allostery that are shared with conventional ligand-gated channels and (ii) the R
      domain modulates CFTR activity independent of ATP-induced NBD dimerization.

PMID- 20133717
TI  - Selective targeting of radiation-resistant tumor-initiating cells.
AB  - Tumor-initiating cells (TICs) have been shown both experimentally and clinically
      to be resistant to radiation and chemotherapy, potentially resulting in residual
      disease that can lead to recurrence. In this study, we demonstrate that TICs
      isolated from p53 null mouse mammary tumors repair DNA damage following in vivo
      ionizing radiation more efficiently than the bulk of the tumor cells. Down
      regulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was
      observed both in fluorescence activated cell sorting (FACS)-isolated TICs as
      compared to non-TICs and in TIC-enriched mammospheres as compared to primary
      tumor cells depleted of TICs. This effect was accompanied by increased Akt
      signaling, as well as by the direct activation of the canonical Wnt/beta-catenin
      signaling pathway specifically within the TIC subpopulation by phosphorylation of
      beta-catenin on serine 552. Using limiting dilution transplantation performed on
      p53 null tumor cells transduced with Wnt reporter lentivirus, we demonstrated
      that FACS sorting of cells expressing TOP-eGFP resulted in a marked enrichment
      for TICs. Furthermore, FACS analysis demonstrated that cells with active Wnt
      signaling overlapped with the TIC subpopulation characterized previously using
      cell surface markers. Finally, pharmacological inhibition of the Akt pathway in
      both mammospheres and syngeneic mice bearing tumors was shown to inhibit
      canonical Wnt signaling as well as the repair of DNA damage selectively in TICs,
      sensitizing them to ionizing radiation treatment. Thus, these results suggest
      that pretreatment with Akt inhibitors before ionizing radiation treatment may be
      of potential therapeutic benefit to patients.

PMID- 20133718
TI  - ProNGF induces TNFalpha-dependent death of retinal ganglion cells through a
      p75NTR non-cell-autonomous signaling pathway.
AB  - Neurotrophin binding to the p75 neurotrophin receptor (p75(NTR)) activates
      neuronal apoptosis following adult central nervous system injury, but the
      underlying cellular mechanisms remain poorly defined. In this study, we show that
      the proform of nerve growth factor (proNGF) induces death of retinal ganglion
      cells in adult rodents via a p75(NTR)-dependent signaling mechanism. Expression
      of p75(NTR) in the adult retina is confined to Muller glial cells; therefore we
      tested the hypothesis that proNGF activates a non-cell-autonomous signaling
      pathway to induce retinal ganglion cell (RGC) death. Consistent with this, we
      show that proNGF induced robust expression of tumor necrosis factor alpha
      (TNFalpha) in Muller cells and that genetic or biochemical ablation of TNFalpha
      blocked proNGF-induced death of retinal neurons. Mice rendered null for p75(NTR),
      its coreceptor sortilin, or the adaptor protein NRAGE were defective in proNGF
      induced glial TNFalpha production and did not undergo proNGF-induced retinal
      ganglion cell death. We conclude that proNGF activates a non-cell-autonomous
      signaling pathway that causes TNFalpha-dependent death of retinal neurons in
      vivo.

PMID- 20133719
TI  - Deceptive chemical signals induced by a plant virus attract insect vectors to
      inferior hosts.
AB  - Previous studies have shown that vector-borne pathogens can alter the phenotypes
      of their hosts and vectors in ways that influence the frequency and nature of
      interactions between them, with significant implications for the transmission and
      spread of disease. For insect-borne pathogens, host odors are particularly likely
      targets for manipulation, because both plant- and animal-feeding insects use
      volatile compounds derived from their hosts as key foraging cues. Here, we
      document the effects of a widespread plant pathogen, Cucumber mosaic virus (CMV),
      on the quality and attractiveness of one of its host plants (Cucurbita pepo cv.
      Dixie) for two aphid vectors, Myzus persicae and Aphis gossypii. Our results
      indicate that CMV greatly reduces host-plant quality-aphids performed poorly on
      infected plants and rapidly emigrated from them-but increases the attractiveness
      of infected plants to aphids by inducing elevated emissions of a plant volatile
      blend otherwise similar to that emitted by healthy plants. Thus, CMV appears to
      attract vectors deceptively to infected plants from which they then disperse
      rapidly, a pattern highly conducive to the nonpersistent transmission mechanism
      employed by CMV and very different from the pattern previously reported for
      persistently transmitted viruses that require sustained aphid feeding for
      transmission. In addition to providing a documented example of a pathogen
      inducing a deceptive signal of host-plant quality to vectors, our results suggest
      that the transmission mechanism is a major factor shaping pathogen-induced
      changes in host-plant phenotypes. Furthermore, our findings yield a general
      hypothesis that, when vector-borne plant or animal pathogens reduce host quality
      for vectors, pathogen-induced changes in host phenotypes that enhance vector
      attraction frequently will involve the exaggeration of existing host-location
      cues.

PMID- 20133720
TI  - Layer-specific variation of iron content in cerebral cortex as a source of MRI
      contrast.
AB  - Recent advances in high-field MRI have dramatically improved the visualization of
      human brain anatomy in vivo. Most notably, in cortical gray matter, strong
      contrast variations have been observed that appear to reflect the local laminar
      architecture. This contrast has been attributed to subtle variations in the
      magnetic properties of brain tissue, possibly reflecting varying iron and myelin
      content. To establish the origin of this contrast, MRI data from postmortem brain
      samples were compared with electron microscopy and histological staining for iron
      and myelin. The results show that iron is distributed over laminae in a pattern
      that is suggestive of each region's myeloarchitecture and forms the dominant
      source of the observed MRI contrast.

PMID- 20133721
TI  - Encoding properties of haltere neurons enable motion feature detection in a
      biological gyroscope.
AB  - The halteres of dipteran insects are essential sensory organs for flight control.
      They are believed to detect Coriolis and other inertial forces associated with
      body rotation during flight. Flies use this information for rapid flight control.
      We show that the primary afferent neurons of the haltere's mechanoreceptors
      respond selectively with high temporal precision to multiple stimulus features.
      Although we are able to identify many stimulus features contributing to the
      response using principal component analysis, predictive models using only two
      features, common across the cell population, capture most of the cells' encoding
      activity. However, different sensitivity to these two features permits each cell
      to respond to sinusoidal stimuli with a different preferred phase. This feature
      similarity, combined with diverse phase encoding, allows the haltere to transmit
      information at a high rate about numerous inertial forces, including Coriolis
      forces.

PMID- 20133722
TI  - Surface organization of aqueous MgCl2 and application to atmospheric marine
      aerosol chemistry.
AB  - Inorganic salts in marine aerosols play an active role in atmospheric chemistry,
      particularly in coastal urban regions. The study of the interactions of these
      ions with water molecules at the aqueous surface helps to elucidate the role of
      inorganic cations and anions in atmospheric processes. We present surface
      vibrational sum frequency generation (SFG) spectroscopic and molecular dynamics
      (MD) studies of aqueous MgCl(2) surfaces as models of marine aerosol.
      Spectroscopy results reveal that the disturbance of the hydrogen bonding
      environment of the air/aqueous interface is dependent on the MgCl(2)
      concentration. At low concentrations (< 1 M) minor changes are observed. At
      concentrations above 1 M the hydrogen bonding environment is highly perturbed.
      The 2.1 M intermediate concentration solution shows the largest SFG response
      relative to the other solutions including concentrations as high as 4.7 M. The
      enhancement of SFG signal observed for the 2.1 M solution is attributed to a
      larger SFG-active interfacial region and more strongly oriented water molecules
      relative to other concentrations. MD simulations reveal concentration dependent
      compression of stratified layers of ions and water orientation differences at
      higher concentrations. SFG and MD studies of the dangling OH of the surface water
      reveal that the topmost water layer is affected structurally at high
      concentrations (> 3.1 M). Finally, the MgCl(2) concentration effect on a fatty
      acid coated aqueous surface was investigated and SFG spectra reveal that
      deprotonation of the carboxylic acid of atmospherically relevant palmitic acid
      (PA) is accompanied by binding of the Mg(2+) to the PA headgroup.

PMID- 20133723
TI  - Visualizing dynamic interaction between calmodulin and calmodulin-related kinases
      via a monitoring method in live mammalian cells.
AB  - A new visualizing method was developed for monitoring protein-protein (P-P)
      interactions in live mammalian cells. P-P interactions are visualized by
      directing localization of a bait protein to endosomes. This method is
      sufficiently robust to analyze signal-dependent P-P interactions such as calcium
      dependent protein interactions. We visualized interactions between activated
      calmodulin and calmodulin-binding proteins, and observed oscillatory interactions
      via time-lapse imaging. In addition, this new method can simultaneously monitor
      multiple P-P interactions in a single live cell, which allows comparison of
      interactions between several prey proteins and a single bait protein. We observed
      that CaMKK1 and CaMKIIalpha bind calmodulin with distinct binding affinities in
      live cell, which indicates that calcium signaling is fine-tuned by distinct
      activation patterns of CaM kinases. This method will enable investigation of
      cellular processes based on dynamic P-P interactions.

PMID- 20133724
TI  - Attribution of climate forcing to economic sectors.
AB  - A much-cited bar chart provided by the Intergovernmental Panel on Climate Change
      displays the climate impact, as expressed by radiative forcing in watts per meter
      squared, of individual chemical species. The organization of the chart reflects
      the history of atmospheric chemistry, in which investigators typically focused on
      a single species of interest. However, changes in pollutant emissions and
      concentrations are a symptom, not a cause, of the primary driver of anthropogenic
      climate change: human activity. In this paper, we suggest organizing the bar
      chart according to drivers of change-that is, by economic sector. Climate impacts
      of tropospheric ozone, fine aerosols, aerosol-cloud interactions, methane, and
      long-lived greenhouse gases are considered. We quantify the future evolution of
      the total radiative forcing due to perpetual constant year 2000 emissions by
      sector, most relevant for the development of climate policy now, and focus on two
      specific time points, near-term at 2020 and long-term at 2100. Because sector
      profiles differ greatly, this approach fosters the development of smart climate
      policy and is useful to identify effective opportunities for rapid mitigation of
      anthropogenic radiative forcing.

PMID- 20133725
TI  - Capillarity-based switchable adhesion.
AB  - Drawing inspiration from the adhesion abilities of a leaf beetle found in nature,
      we have engineered a switchable adhesion device. The device combines two
      concepts: The surface tension force from a large number of small liquid bridges
      can be significant (capillarity-based adhesion) and these contacts can be quickly
      made or broken with electronic control (switchable). The device grabs or releases
      a substrate in a fraction of a second via a low-voltage pulse that drives
      electroosmotic flow. Energy consumption is minimal because both the grabbed and
      released states are stable equilibria that persist with no energy added to the
      system. Notably, the device maintains the integrity of an array of hundreds to
      thousands of distinct interfaces during active reconfiguration from droplets to
      bridges and back, despite the natural tendency of the liquid toward coalescence.
      We demonstrate the scaling of adhesion strength with the inverse of liquid
      contact size. This suggests that strengths approaching those of permanent bonding
      adhesives are possible as feature size is scaled down. In addition,
      controllability is fast and efficient because the attachment time and required
      voltage also scale down favorably. The device features compact size, no solid
      moving parts, and is made of common materials.

PMID- 20133726
TI  - Identifying the amylome, proteins capable of forming amyloid-like fibrils.
AB  - The amylome is the universe of proteins that are capable of forming amyloid-like
      fibrils. Here we investigate the factors that enable a protein to belong to the
      amylome. A major factor is the presence in the protein of a segment that can form
      a tightly complementary interface with an identical segment, which permits the
      formation of a steric zipper-two self-complementary beta sheets that form the
      spine of an amyloid fibril. Another factor is sufficient conformational freedom
      of the self-complementary segment to interact with other molecules. Using RNase A
      as a model system, we validate our fibrillogenic predictions by the 3D profile
      method based on the crystal structure of NNQQNY and demonstrate that a specific
      residue order is required for fiber formation. Our genome-wide analysis revealed
      that self-complementary segments are found in almost all proteins, yet not all
      proteins form amyloids. The implication is that chaperoning effects have evolved
      to constrain self-complementary segments from interaction with each other.

PMID- 20133727
TI  - FragBag, an accurate representation of protein structure, retrieves structural
      neighbors from the entire PDB quickly and accurately.
AB  - Fast identification of protein structures that are similar to a specified query
      structure in the entire Protein Data Bank (PDB) is fundamental in structure and
      function prediction. We present FragBag: An ultrafast and accurate method for
      comparing protein structures. We describe a protein structure by the collection
      of its overlapping short contiguous backbone segments, and discretize this set
      using a library of fragments. Then, we succinctly represent the protein as a
      "bags-of-fragments"-a vector that counts the number of occurrences of each
      fragment-and measure the similarity between two structures by the similarity
      between their vectors. Our representation has two additional benefits: (i) it can
      be used to construct an inverted index, for implementing a fast structural search
      engine of the entire PDB, and (ii) one can specify a structure as a collection of
      substructures, without combining them into a single structure; this is valuable
      for structure prediction, when there are reliable predictions only of parts of
      the protein. We use receiver operating characteristic curve analysis to quantify
      the success of FragBag in identifying neighbor candidate sets in a dataset of
      over 2,900 structures. The gold standard is the set of neighbors found by six
      state of the art structural aligners. Our best FragBag library finds more
      accurate candidate sets than the three other filter methods: The SGM, PRIDE, and
      a method by Zotenko et al. More interestingly, FragBag performs on a par with the
      computationally expensive, yet highly trusted structural aligners STRUCTAL and
      CE.

PMID- 20133728
TI  - Switchable hardening of a ferromagnet at fixed temperature.
AB  - The intended use of a magnetic material, from information storage to power
      conversion, depends crucially on its domain structure, traditionally crafted
      during materials synthesis. By contrast, we show that an external magnetic field,
      applied transverse to the preferred magnetization of a model disordered uniaxial
      ferromagnet, is an isothermal regulator of domain pinning. At elevated
      temperatures, near the transition into the paramagnet, modest transverse fields
      increase the pinning, stabilize the domain structure, and harden the magnet,
      until a point where the field induces quantum tunneling of the domain walls and
      softens the magnet. At low temperatures, tunneling completely dominates the
      domain dynamics and provides an interpretation of the quantum phase transition in
      highly disordered magnets as a localization/delocalization transition for domain
      walls. While the energy scales of the rare earth ferromagnet studied here
      restrict the effects to cryogenic temperatures, the principles discovered are
      general and should be applicable to existing classes of highly anisotropic
      ferromagnets with ordering at room temperature or above.

PMID- 20133729
TI  - STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells
      exposed to oxidative stress.
AB  - We provide unprecedented genetic and biochemical evidence that the antiapoptotic
      transcription factor STAT3 serves as a substrate for SYK tyrosine kinase both in
      vitro and in vivo. Induction of SYK in an ecdysone-inducible mammalian expression
      system results in STAT3 activation, as documented by tyrosine phosphorylation and
      nuclear translocation of STAT3, as well as amplified expression of several STAT3
      target genes. STAT3 activation after oxidative stress (OS) is strongly diminished
      in DT40 chicken B-lineage lymphoma cells rendered SYK-deficient by targeted
      disruption of the syk gene. Introduction of a wild-type, C-terminal or N-terminal
      SH2 domain-mutated, but not a kinase domain-mutated, syk gene into SYK-deficient
      DT40 cells restores OS-induced enhancement of STAT-3 activity. Thus, SYK plays an
      important and indispensable role in OS-induced STAT3 activation and its catalytic
      SH1 domain is critical for this previously unknown regulatory function. These
      results provide evidence for the existence of a novel mode of cytokine
      independent cross-talk that operates between SYK and STAT3 pathways and regulates
      apoptosis during OS. We further provide experimental evidence that SYK is capable
      of associating with and phosphorylating STAT3 in human B-lineage
      leukemia/lymphoma cells challenged with OS. In agreement with a prerequisite role
      of SYK in OS-induced STAT3 activation, OS does not induce tyrosine
      phosphorylation of STAT3 in SYK-deficient human proB leukemia cells. Notably,
      inhibition of SYK with a small molecule drug candidate prevents OS-induced
      activation of STAT3 and overcomes the resistance of human B-lineage
      leukemia/lymphoma cells to OS-induced apoptosis.

PMID- 20133730
TI  - Competition between native topology and nonnative interactions in simple and
      complex folding kinetics of natural and designed proteins.
AB  - We compared folding properties of designed protein Top7 and natural protein S6 by
      using coarse-grained chain models with a mainly native-centric construct that
      accounted also for nonnative hydrophobic interactions and desolvation barriers.
      Top7 and S6 have similar secondary structure elements and are approximately equal
      in length and hydrophobic composition. Yet their experimental folding kinetics
      were drastically different. Consistent with experiment, our simulated folding
      chevron arm for Top7 exhibited a severe rollover, whereas that for S6 was
      essentially linear, and Top7 model kinetic relaxation was multiphasic under
      strongly folding conditions. The peculiar behavior of Top7 was associated with
      several classes of kinetic traps in our model. Significantly, the amino acid
      residues participating in nonnative interactions in trapped conformations in our
      Top7 model overlapped with those deduced experimentally. These affirmations
      suggest that the simple ingredients of native topology plus sequence-dependent
      nonnative interactions are sufficient to account for some key features of protein
      folding kinetics. Notably, when nonnative interactions were absent in the model,
      Top7 chevron rollover was not correctly predicted. In contrast, nonnative
      interactions had little effect on the quasi linearity of the model folding
      chevron arm for S6. This intriguing distinction indicates that folding
      cooperativity is governed by a subtle interplay between the sequence-dependent
      driving forces for native topology and the locations of favorable nonnative
      interactions entailed by the same sequence. Constructed with a capability to
      mimic this interplay, our simple modeling approach should be useful in general
      for assessing a designed sequence's potential to fold cooperatively.

PMID- 20133731
TI  - Human stem cell delivery for treatment of large segmental bone defects.
AB  - Local or systemic stem cell delivery has the potential to promote repair of a
      variety of damaged or degenerated tissues. Although various stem cell sources
      have been investigated for bone repair, few comparative reports exist, and
      cellular distribution and viability postimplantation remain key issues. In this
      study, we quantified the ability of tissue-engineered constructs containing
      either human fetal or adult stem cells to enhance functional repair of nude rat
      critically sized femoral defects. After 12 weeks, defects treated with cell
      seeded polymer scaffolds had significantly higher bone ingrowth and torsional
      strength compared to those receiving acellular scaffolds, although there were no
      significant differences between the cell sources. Next, stem cells were labeled
      with fluorescent quantum dots (QDs) in an attempt to noninvasively track their
      distribution after delivery on scaffolds. Clear fluorescence was observed at
      implantation sites throughout the study; however, beginning 7-10 days after
      surgery, signals were also observed at contralateral sites treated with acellular
      QD-free scaffolds. Although immunostaining for human nuclei revealed retention of
      some cells at the implantation site, no human cells were detected in the control
      limb defects. Additional histological analysis of implantation and control defect
      tissues revealed macrophages containing endocytosed QDs. Furthermore, QD-labeling
      appeared to diminish transplanted cell function resulting in reduced healing
      responses. In summary, augmentation of polymeric scaffolds with stem cells
      derived from fetal and adult tissues significantly enhanced healing of large
      segmental bone defects; however, QD labeling of stem cells eliminated the
      observed therapeutic effect and failed to conclusively track stem cell location
      long-term in vivo.

PMID- 20133732
TI  - Political economy of marine reserves: understanding the role of opportunity
      costs.
AB  - The creation of marine reserves is often controversial. For decisionmakers,
      trying to find compromises, an understanding of the timing, magnitude, and
      incidence of the costs of a reserve is critical. Understanding the costs, in
      turn, requires consideration of not just the direct financial costs but also the
      opportunity costs associated with reserves. We use a discrete choice model of
      commercial fishermen's behavior to examine both the short-run and long-run
      opportunity costs of marine reserves. Our results can help policymakers recognize
      the factors influencing commercial fishermen's responses to reserve proposals.
      More generally, we highlight the potential drivers behind the political economy
      of marine reserves.

PMID- 20133733
TI  - Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate.
AB  - Boundaries between euchromatic and heterochromatic regions until now have been
      associated with chromatin-opening activities. Here, we identified an unexpected
      role for histone deacetylation in this process. Significantly, the histone
      deacetylase (HDAC) Rpd3 was necessary for boundary formation in Saccharomyces
      cerevisiae. rpd3Delta led to silent information regulator (SIR) spreading and
      repression of subtelomeric genes. In the absence of a known boundary factor, the
      histone acetyltransferase complex SAS-I, rpd3Delta caused inappropriate SIR
      spreading that was lethal to yeast cells. Notably, Rpd3 was capable of creating a
      boundary when targeted to heterochromatin. Our data suggest a mechanism for
      boundary formation whereby histone deacetylation by Rpd3 removes the substrate
      for the HDAC Sir2, so that Sir2 no longer can produce O-acetyl-ADP ribose
      (OAADPR) by consumption of NAD(+) in the deacetylation reaction. In essence,
      OAADPR therefore is unavailable for binding to Sir3, preventing SIR propagation.

PMID- 20133734
TI  - Kupfer-type immunological synapse characteristics do not predict anti-brain tumor
      cytolytic T-cell function in vivo.
AB  - To analyze the in vivo structure of antigen-specific immunological synapses
      during an effective immune response, we established brain tumors expressing the
      surrogate tumor antigen ovalbumin and labeled antigen-specific anti-glioma T
      cells using specific tetramers. Using these techniques, we determined that a
      significant number of antigen-specific T cells were localized to the brain tumor
      and surrounding brain tissue and a large percentage could be induced to express
      IFNgamma when exposed to the specific ovalbumin-derived peptide epitope SIINFEKL.
      Detailed morphological analysis of T cells immunoreactive for tetramers in direct
      physical contact with tumor cells expressing ovalbumin indicated that the
      interface between T cells and target tumor cells displayed various morphologies,
      including Kupfer-type immunological synapses. Quantitative analysis of adjacent
      confocal optical sections was performed to determine if the higher frequency of
      antigen-specific antiglioma T cells present in animals that developed an
      effective antitumor immune response could be correlated with a specific
      immunological synaptic morphology. Detailed in vivo quantitative analysis failed
      to detect an increased proportion of immunological synapses displaying the
      characteristic Kupfer-type morphology in animals mounting a strong and effective
      antitumor immune response as compared with those experiencing a clinically
      ineffective response. We conclude that an effective cytolytic immune response is
      not dependent on an increased frequency of Kupfer-type immunological synapses
      between T cells and tumor cells.

PMID- 20133735
TI  - Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and
      virulence genes in Mycobacterium tuberculosis.
AB  - Bacterial nucleoid-associated proteins play important roles in chromosome
      organization and global gene regulation. We find that Lsr2 of Mycobacterium
      tuberculosis is a unique nucleoid-associated protein that binds AT-rich regions
      of the genome, including genomic islands acquired by horizontal gene transfer and
      regions encoding major virulence factors, such as the ESX secretion systems, the
      lipid virulence factors PDIM and PGL, and the PE/PPE families of antigenic
      proteins. Comparison of genome-wide binding data with expression data indicates
      that Lsr2 binding results in transcriptional repression. Domain-swapping
      experiments demonstrate that Lsr2 has an N-terminal dimerization domain and a C
      terminal DNA-binding domain. Nuclear magnetic resonance analysis of the DNA
      binding domain of Lsr2 and its interaction with DNA reveals a unique structure
      and a unique mechanism that enables Lsr2 to discriminately target AT-rich
      sequences through interactions with the minor groove of DNA. Taken together, we
      provide evidence that mycobacteria have employed a structurally distinct molecule
      with an apparently different DNA recognition mechanism to achieve a function
      similar to the Enterobacteriaceae H-NS, likely coordinating global gene
      regulation and virulence in this group of medically important bacteria.

PMID- 20133736
TI  - Formation and dissociation of M1 muscarinic receptor dimers seen by total
      internal reflection fluorescence imaging of single molecules.
AB  - G-protein-coupled receptors (GPCRs) are the largest family of transmembrane
      signaling proteins in the human genome. Events in the GPCR signaling cascade have
      been well characterized, but the receptor composition and its membrane
      distribution are still generally unknown. Although there is evidence that some
      members of the GPCR superfamily exist as constitutive dimers or higher oligomers,
      interpretation of the results has been disputed, and recent studies indicate that
      monomeric GPCRs may also be functional. Because there is controversy within the
      field, to address the issue we have used total internal reflection fluorescence
      microscopy (TIRFM) in living cells to visualize thousands of individual molecules
      of a model GPCR, the M(1) muscarinic acetylcholine receptor. By tracking the
      position of individual receptors over time, their mobility, clustering, and
      dimerization kinetics could be directly determined with a resolution of
      approximately 30 ms and approximately 20 nm. In isolated CHO cells, receptors are
      randomly distributed over the plasma membrane. At any given time, approximately
      30% of the receptor molecules exist as dimers, and we found no evidence for
      higher oligomers. Two-color TIRFM established the dynamic nature of dimer
      formation with M(1) receptors undergoing interconversion between monomers and
      dimers on the timescale of seconds.

PMID- 20133737
TI  - Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells
      clarifies their roles in tumor growth regulation.
AB  - Phosphotidylinositol-3-kinase (PI3K) signaling is altered in the majority of
      human cancers. To gain insight into the roles of members of this pathway in
      growth regulation, we inactivated AKT1, AKT2, or PDPK1 genes by targeted
      homologous recombination in human colon cancer cell lines. Knockout of either
      AKT1 or AKT2 had minimum effects on cell growth or downstream signaling. In
      contrast, knockout of both AKT1 and AKT2 resulted in markedly reduced
      proliferation in vitro when growth factors were limiting and severely affected
      experimental metastasis in mice. Unexpectedly, AKT1 and AKT2 appeared to regulate
      growth through FOXO proteins, but not through either GSK3beta or mTOR. In
      contrast, inactivation of PDPK1 affected GSK3beta and mTOR activation. These
      findings show that the PI3K signaling pathway is wired differently in human
      cancer cells than in other cell types or organisms, which has important
      implications for the design and testing of drugs that target this pathway.

PMID- 20133738
TI  - Functional organization of motor cortex of adult macaque monkeys is altered by
      sensory loss in infancy.
AB  - When somatosensory cortex (S1) is deprived of some of its inputs after section of
      ascending afferents in the dorsal columns of the spinal cord, it reorganizes to
      overrepresent the surviving inputs. As somatosensory cortex provides guiding
      sensory information to motor cortex, such sensory loss and representational
      reorganization could affect the development of the motor map in primary motor
      cortex (M1), especially if the sensory loss occurs early in development. To
      address this possibility, the dorsal columns of the spinal cord were sectioned
      between cervical levels (C3-5) 3-12 days after birth in five macaque monkeys.
      After 3-5 years of maturation (young adults), we determined how movements were
      represented in M1 contralateral to the lesion by using microelectrodes to
      electrically stimulate sites in M1 to evoke movements. Although the details of
      the motor maps in these five monkeys varied, the forelimb motor maps were
      abnormal. The representations of digit movements were reduced and abnormally
      arranged. Current levels for evoking movements from the forelimb region of M1
      were in the normal range, but the lowest mean stimulation thresholds were for
      wrist or elbow instead of digit movements. Incomplete lesions and bilateral
      lesions produced fewer abnormalities. The results suggest that the development of
      normal motor cortex maps in M1 depends on sensory feedback from somatosensory
      maps.

PMID- 20133739
TI  - MicroRNA-19a mediates the suppressive effect of laminar flow on cyclin D1
      expression in human umbilical vein endothelial cells.
AB  - Endothelial cells (ECs) respond to changes in mechanical forces, leading to the
      modulation of signaling networks and cell function; an example is the inhibition
      of EC proliferation by steady laminar flow. MicroRNAs (miRs) are short noncoding
      20-22 nucleotide RNAs that negatively regulate the expression of target genes at
      the posttranscriptional level. This study demonstrates that miRs are involved in
      the flow regulation of gene expression in ECs. With the use of microRNA chip
      array, we found that laminar shear stress (12 dyn/cm(2), 12 h) regulated the EC
      expression of many miRs, including miR-19a. We further showed that stable
      transfection of miR-19a significantly decreased the expression of a reporter gene
      controlled by a conserved 3'-untranslated region of the cyclinD1 gene and also
      the protein level of cyclin D1, leading to an arrest of cell cycle at G1/S
      transition. Laminar flow suppressed cyclin D1 protein level, and this suppressive
      effect was diminished when the endogenous miR-19a was inhibited. In conclusion,
      we demonstrated that miR-19a plays an important role in the flow regulation of
      cyclin D1 expression. These results revealed a mechanism by which mechanical
      forces modulate endothelial gene expression.

PMID- 20133740
TI  - Delivery of foreign antigens by engineered outer membrane vesicle vaccines.
AB  - As new disease threats arise and existing pathogens grow resistant to
      conventional interventions, attention increasingly focuses on the development of
      vaccines to induce protective immune responses. Given their admirable safety
      records, protein subunit vaccines are attractive for widespread immunization, but
      their disadvantages include poor immunogenicity and expensive manufacture. We
      show here that engineered Escherichia coli outer membrane vesicles (OMVs) are an
      easily purified vaccine-delivery system capable of greatly enhancing the
      immunogenicity of a low-immunogenicity protein antigen without added adjuvants.
      Using green-fluorescent protein (GFP) as the model subunit antigen, genetic
      fusion of GFP with the bacterial hemolysin ClyA resulted in a chimeric protein
      that elicited strong anti-GFP antibody titers in immunized mice, whereas
      immunization with GFP alone did not elicit such titers. Harnessing the specific
      secretion of ClyA to OMVs, the ClyA-GFP fusion was found localized in OMVs,
      resulting in engineered recombinant OMVs. The anti-GFP humoral response in mice
      immunized with the engineered OMV formulations was indistinguishable from the
      response to the purified ClyA-GFP fusion protein alone and equal to purified
      proteins absorbed to aluminum hydroxide, a standard adjuvant. In a major
      improvement over current practice, engineered OMVs containing ClyA-GFP were
      easily isolated by ultracentrifugation, effectively eliminating the need for
      laborious antigen purification from cell-culture expression systems. With the
      diverse collection of heterologous proteins that can be functionally localized
      with OMVs when fused with ClyA, this work signals the possibility of OMVs as a
      robust and tunable technology platform for a new generation of prophylactic and
      therapeutic vaccines.

PMID- 20133741
TI  - Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial
      cell growth.
AB  - MicroRNAs (miRs) can regulate many cellular functions, but their roles in
      regulating responses of vascular endothelial cells (ECs) to mechanical stimuli
      remain unexplored. We hypothesize that the physiological responses of ECs are
      regulated by not only mRNA and protein signaling networks, but also expression of
      the corresponding miRs. EC growth arrest induced by pulsatile shear (PS) flow is
      an important feature for flow regulation of ECs. miR profiling showed that 21
      miRs are differentially expressed (8 up- and 13 downregulated) in response to 24
      h PS as compared to static condition (ST). The mRNA expression profile indicates
      EC growth arrest under 24-h PS. Analysis of differentially expressed miRs yielded
      68 predicted mRNA targets that overlapped with results of microarray mRNA
      profiling. Functional analysis of miR profile indicates that the cell cycle
      network is highly regulated. The upregulation of miR-23b and miR-27b was found to
      correlate with the PS-induced EC growth arrest. Inhibition of miR-23b using
      antagomir-23b oligonucleotide (AM23b) reversed the PS-induced E2F1 reduction and
      retinoblastoma (Rb) hypophosphorylation and attenuated the PS-induced G1/G0
      arrest. Antagomir AM27b regulated E2F1 expression, but did not affect Rb and
      growth arrest. Our findings indicate that PS suppresses EC proliferation through
      the regulation of miR-23b and provide insights into the role of miRs in
      mechanotransduction.

PMID- 20133742
TI  - Molecular mimics can induce a nonautoaggressive repertoire that preempts
      induction of autoimmunity.
AB  - To determine the role that competition plays in a molecular mimic's capacity to
      induce autoimmunity, we studied the ability of naive encephalitogenic T cells to
      expand in response to agonist altered peptide ligands (APLs), some capable of
      stimulating both self-directed and exclusively APL-specific T cells. Our results
      show that although the APLs capable of stimulating exclusively APL-specific T
      cells are able to expand encephalitogenic T cells in vitro, the encephalitogenic
      repertoire is effectively outcompeted in vivo when the APL is used as the priming
      immunogen. Competition as a mechanism was supported by: (i) the demonstration of
      a population of exclusively APL-specific T cells, (ii) an experiment in which an
      encephalitogenic T cell population was successfully outcompeted by adoptively
      transferred naive T cells, and (iii) demonstrating that the elimination of
      competing T cells bestowed an APL with the ability to expand naive
      encephalitogenic T cells in vivo. In total, these experiments support the
      existence of a reasonably broad T cell repertoire responsive to a molecular mimic
      (e.g., a microbial agent), of which the exclusively mimic-specific component
      tends to focus the immune response on the invading pathogen, whereas the rare
      cross-reactive, potentially autoreactive T cells are often preempted from
      becoming involved.

PMID- 20133743
TI  - Keap1 is a forked-stem dimer structure with two large spheres enclosing the
      intervening, double glycine repeat, and C-terminal domains.
AB  - Keap1 is a substrate adaptor of a Cullin 3-based E3 ubiquitin ligase complex that
      recognizes Nrf2, and also acts as a cellular sensor for xenobiotics and oxidative
      stresses. Nrf2 is a transcriptional factor regulating the expression of
      cytoprotective enzyme genes in response to such stresses. Under unstressed
      conditions Keap1 binds Nrf2 and results in rapid degradation of Nrf2 through the
      proteasome pathway. In contrast, upon exposure to oxidative and electrophilic
      stress, reactive cysteine residues in intervening region (IVR) and Broad complex,
      Tramtrack, and Bric-a-Brac domains of Keap1 are modified by electrophiles. This
      modification prevents Nrf2 from rapid degradation and induces Nrf2 activity by
      repression of Keap1. Here we report the structure of mouse Keap1 homodimer by
      single particle electron microscopy. Three-dimensional reconstruction at 24-A
      resolution revealed two large spheres attached by short linker arms to the sides
      of a small forked-stem structure, resembling a cherry-bob. Each sphere has a
      tunnel corresponding to the central hole of the beta-propeller domain, as
      determined by x-ray crystallography. The IVR domain appears to surround the core
      of the beta-propeller domain. The unexpected proximity of IVR to the beta
      propeller domain suggests that any distortions generated during modification of
      reactive cysteine residues in the IVR domain may send a derepression signal to
      the beta-propeller domain and thereby stabilize Nrf2. This study thus provides a
      structural basis for the two-site binding and hinge-latch model of stress sensing
      by the Nrf2-Keap1 system.

PMID- 20133744
TI  - Modeling the emergence of universality in color naming patterns.
AB  - The empirical evidence that human color categorization exhibits some universal
      patterns beyond superficial discrepancies across different cultures is a major
      breakthrough in cognitive science. As observed in the World Color Survey (WCS),
      indeed, any two groups of individuals develop quite different categorization
      patterns, but some universal properties can be identified by a statistical
      analysis over a large number of populations. Here, we reproduce the WCS in a
      numerical model in which different populations develop independently their own
      categorization systems by playing elementary language games. We find that a
      simple perceptual constraint shared by all humans, namely the human Just
      Noticeable Difference (JND), is sufficient to trigger the emergence of universal
      patterns that unconstrained cultural interaction fails to produce. We test the
      results of our experiment against real data by performing the same statistical
      analysis proposed to quantify the universal tendencies shown in the WCS [Kay P &
      Regier T. (2003) Proc. Natl. Acad. Sci. USA 100: 9085-9089], and obtain an
      excellent quantitative agreement. This work confirms that synthetic modeling has
      nowadays reached the maturity to contribute significantly to the ongoing debate
      in cognitive science.

PMID- 20133745
TI  - PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that
      links force and catalysis.
AB  - PR65 is the two-layered (alpha-alpha solenoid) HEAT-repeat (Huntingtin,
      elongation factor 3, a subunit of protein phosphatase 2A, PI3 kinase target of
      rapamycin 1) scaffold of protein phosphatase PP2A. Molecular dynamics simulations
      predict that, at forces expected in living systems, PR65 undergoes (visco
      )elastic deformations in response to pulling/pushing on its ends. At lower
      forces, smooth global flexural and torsional changes occur via even
      redistribution of stress along the hydrophobic core of the molecule. At
      intermediate forces, helix-helix separation along one layer ("fracturing") leads
      to global relaxation plus loss of contact in the other layer to unstack the
      affected units. Fracture sites are determined by unusual sequences in contiguous
      interhelix turns. Normal mode analysis of the heterotrimeric PP2A enzyme reveals
      that its ambient conformational fluctuations are dominated by elastic
      deformations of PR65, which introduce a mechanical linkage between the separately
      bound regulatory and catalytic subunits. PR65-dominated fluctuations of PP2A have
      the effect of opening and closing the enzyme's substrate binding/catalysis
      interface, as well as altering the positions of certain catalytic residues. These
      results suggest that substrate binding/catalysis are sensitive to mechanical
      force. Force could be imposed from the outside (e.g., in PP2A's response to
      spindle tension) or arise spontaneously (e.g., in PP2A's interaction with
      unstructured proteins such as Tau, a microtubule-associated Alzheimer's
      implicated protein). The presented example supports the view that conformation
      and function of protein complexes can be modulated by mechanical energy inputs,
      as well as by chemical energy inputs from ligand binding. Given that helical
      repeat proteins are involved in many cellular processes, the findings also
      encourage the view that mechanical forces may be of widespread importance.

PMID- 20133746
TI  - The AAA+ ClpX machine unfolds a keystone subunit to remodel the Mu transpososome.
AB  - A hyperstable complex of the tetrameric MuA transposase with recombined DNA must
      be remodeled to allow subsequent DNA replication. ClpX, a AAA+ enzyme, fulfills
      this function by unfolding one transpososome subunit. Which MuA subunit is
      extracted, and how complex destabilization relates to establishment of the
      correct directionality (left to right) of Mu replication, is not known. Here,
      using altered-specificity MuA proteins/DNA sites, we demonstrate that
      transpososome destabilization requires preferential ClpX unfolding of either the
      catalytic-left or catalytic-right subunits, which make extensive intersubunit
      contacts in the tetramer. In contrast, ClpX recognizes the other two subunits in
      the tetramer much less efficiently, and their extraction does not substantially
      destabilize the complex. Thus, ClpX targets the most stable structural components
      of the complex. Left-end biased Mu replication is not, however, determined by
      ClpX's intrinsic subunit preference. The specific targeting of a stabilizing
      "keystone subunit" within a complex for unfolding is an attractive general
      mechanism for remodeling by AAA+ enzymes.

PMID- 20133747
TI  - NMR and XAS reveal an inner-sphere metal binding site in the P4 helix of the
      metallo-ribozyme ribonuclease P.
AB  - Functionally critical metals interact with RNA through complex coordination
      schemes that are currently difficult to visualize at the atomic level under
      solution conditions. Here, we report a new approach that combines NMR and XAS to
      resolve and characterize metal binding in the most highly conserved P4 helix of
      ribonuclease P (RNase P), the ribonucleoprotein that catalyzes the divalent metal
      ion-dependent maturation of the 5' end of precursor tRNA. Extended X-ray
      absorption fine structure (EXAFS) spectroscopy reveals that the Zn(2+) bound to a
      P4 helix mimic is six-coordinate, with an average Zn-O/N bond distance of 2.08 A.
      The EXAFS data also show intense outer-shell scattering indicating that the zinc
      ion has inner-shell interactions with one or more RNA ligands. NMR Mn(2+)
      paramagnetic line broadening experiments reveal strong metal localization at
      residues corresponding to G378 and G379 in B. subtilis RNase P. A new "metal
      cocktail" chemical shift perturbation strategy involving titrations with ,
      Zn(2+), and confirm an inner-sphere metal interaction with residues G378 and
      G379. These studies present a unique picture of how metals coordinate to the
      putative RNase P active site in solution, and shed light on the environment of an
      essential metal ion in RNase P. Our experimental approach presents a general
      method for identifying and characterizing inner-sphere metal ion binding sites in
      RNA in solution.

PMID- 20133748
TI  - Spatio-temporal correlations can drastically change the response of a MAPK
      pathway.
AB  - Multisite covalent modification of proteins is omnipresent in eukaryotic cells. A
      well-known example is the mitogen-activated protein kinase (MAPK) cascade where,
      in each layer of the cascade, a protein is phosphorylated at two sites. It has
      long been known that the response of a MAPK pathway strongly depends on whether
      the enzymes that modify the protein act processively or distributively. A
      distributive mechanism, in which the enzyme molecules have to release the
      substrate molecules in between the modification of the two sites, can generate an
      ultrasensitive response and lead to hysteresis and bistability. We study by
      Green's Function Reaction Dynamics (GFRD), a stochastic scheme that makes it
      possible to simulate biochemical networks at the particle level in time and
      space, a dual phosphorylation cycle in which the enzymes act according to a
      distributive mechanism. We find that the response of this network can differ
      dramatically from that predicted by a mean-field analysis based on the chemical
      rate equations. In particular, rapid rebindings of the enzyme molecules to the
      substrate molecules after modification of the first site can markedly speed up
      the response and lead to loss of ultrasensitivity and bistability. In essence,
      rapid enzyme-substrate rebindings can turn a distributive mechanism into a
      processive mechanism. We argue that slow ADP release by the enzymes can protect
      the system against these rapid rebindings, thus enabling ultrasensitivity and
      bistability.

PMID- 20133749
TI  - Structural basis of the oxidative activation of the carboxysomal gamma-carbonic
      anhydrase, CcmM.
AB  - Cyanobacterial RuBisCO is sequestered in large, icosahedral, protein-bounded
      microcompartments called carboxysomes. Bicarbonate is pumped into the cytosol,
      diffuses into the carboxysome through small pores in its shell, and is then
      converted to CO(2) by carbonic anhydrase (CA) prior to fixation. Paradoxically,
      many beta-cyanobacteria, including Thermosynechococcus elongatus BP-1, lack the
      conventional carboxysomal beta-CA, ccaA. The N-terminal domain of the
      carboxysomal protein CcmM is homologous to gamma-CA from Methanosarcina
      thermophila (Cam) but recombinant CcmM derived from ccaA-containing cyanobacteria
      show no CA activity. We demonstrate here that either full length CcmM from T.
      elongatus, or a construct truncated after 209 residues (CcmM209), is active as a
      CA-the first catalytically active bacterial gamma-CA reported. The 2.0 A
      structure of CcmM209 reveals a trimeric, left-handed beta-helix structure that
      closely resembles Cam, except that residues 198-207 form a third alpha-helix
      stabilized by an essential Cys194-Cys200 disulfide bond. Deleting residues 194
      209 (CcmM193) results in an inactive protein whose 1.1 A structure shows
      disordering of the N- and C-termini, and reorganization of the trimeric interface
      and active site. Under reducing conditions, CcmM209 is similarly partially
      disordered and inactive as a CA. CcmM protein in fresh E. coli cell extracts is
      inactive, implying that the cellular reducing machinery can reduce and inactivate
      CcmM, while diamide, a thiol oxidizing agent, activates the enzyme. Thus, like
      membrane-bound eukaryotic cellular compartments, the beta-carboxysome appears to
      be able to maintain an oxidizing interior by precluding the entry of thioredoxin
      and other endogenous reducing agents.

PMID- 20133750
TI  - Chemoresponsive assemblies of microparticles at liquid crystalline interfaces.
AB  - Assemblies formed by solid particles at interfaces have been widely studied
      because they serve as models of molecular phenomena, including molecular self
      assembly. Solid particles adsorbed at interfaces also provide a means of
      stabilizing liquid-liquid emulsions and synthesizing materials with tunable
      mechanical, optical, or electronic properties. Whereas many past studies have
      investigated colloids at interfaces of isotropic liquids, recently, new types of
      intercolloidal interactions have been unmasked at interfaces of liquid crystals
      (LCs): The long-range ordering of the LCs, as well as defects within the LCs,
      mediates intercolloidal interactions with symmetries that differ from those
      observed with isotropic liquids. Herein, we report the decoration of interfaces
      formed between aqueous phases and nematic LCs with prescribed densities of solid,
      micrometer-sized particles. The microparticles assemble into chains with
      controlled interparticle spacing, consistent with the dipolar symmetry of the
      defects observed to form about each microparticle. Addition of a molecular
      surfactant to the aqueous phase results in a continuous ordering transition in
      the LC, which triggers reorganization of the microparticles, first by increasing
      the spacing between microparticles within chains and ultimately by forming two
      dimensional arrays with local hexagonal symmetry. The ordering transition of the
      microparticles is reversible and is driven by surfactant-induced changes in the
      symmetry of the topological defects induced by the microparticles. These results
      demonstrate that the orderings of solid microparticles and molecular adsorbates
      are strongly coupled at the interfaces of LCs and that LCs offer the basis of
      methods for reversible, chemosensitive control of the interfacial organization of
      solid microparticles.

PMID- 20133751
TI  - Ultrafast solvation dynamics at binding and active sites of photolyases.
AB  - Dynamic solvation at binding and active sites is critical to protein recognition
      and enzyme catalysis. We report here the complete characterization of ultrafast
      solvation dynamics at the recognition site of photoantenna molecule and at the
      active site of cofactor/substrate in enzyme photolyase by examining femtosecond
      resolved fluorescence dynamics and the entire emission spectra. With direct use
      of intrinsic antenna and cofactor chromophores, we observed the local environment
      relaxation on the time scales from a few picoseconds to nearly a nanosecond.
      Unlike conventional solvation where the Stokes shift is apparent, we observed
      obvious spectral shape changes with the minor, small, and large spectral shifts
      in three function sites. These emission profile changes directly reflect the
      modulation of chromophore's excited states by locally constrained protein and
      trapped-water collective motions. Such heterogeneous dynamics continuously tune
      local configurations to optimize photolyase's function through resonance energy
      transfer from the antenna to the cofactor for energy efficiency and then electron
      transfer between the cofactor and the substrate for repair of damaged DNA. Such
      unusual solvation and synergetic dynamics should be general in function sites of
      proteins.

PMID- 20133752
TI  - Agmatidine, a modified cytidine in the anticodon of archaeal tRNA(Ile), base
      pairs with adenosine but not with guanosine.
AB  - Modification of the cytidine in the first anticodon position of the AUA decoding
      tRNA(Ile) (tRNA2(Ile)) of bacteria and archaea is essential for this tRNA to read
      the isoleucine codon AUA and to differentiate between AUA and the methionine
      codon AUG. To identify the modified cytidine in archaea, we have purified this
      tRNA species from Haloarcula marismortui, established its codon reading
      properties, used liquid chromatography-mass spectrometry (LC-MS) to map RNase A
      and T1 digestion products onto the tRNA, and used LC-MS/MS to sequence the
      oligonucleotides in RNase A digests. These analyses revealed that the
      modification of cytidine in the anticodon of tRNA2(Ile) adds 112 mass units to
      its molecular mass and makes the glycosidic bond unusually labile during mass
      spectral analyses. Accurate mass LC-MS and LC-MS/MS analysis of total nucleoside
      digests of the tRNA2(Ile) demonstrated the absence in the modified cytidine of
      the C2-oxo group and its replacement by agmatine (decarboxy-arginine) through a
      secondary amine linkage. We propose the name agmatidine, abbreviation C(+), for
      this modified cytidine. Agmatidine is also present in Methanococcus maripaludis
      tRNA2(Ile) and in Sulfolobus solfataricus total tRNA, indicating its probable
      occurrence in the AUA decoding tRNA(Ile) of euryarchaea and crenarchaea. The
      identification of agmatidine shows that bacteria and archaea have developed very
      similar strategies for reading the isoleucine codon AUA while discriminating
      against the methionine codon AUG.

PMID- 20133753
TI  - Asymmetric receptor contact is required for tyrosine autophosphorylation of
      fibroblast growth factor receptor in living cells.
AB  - Tyrosine autophosphorylation of receptor tyrosine kinases plays a critical role
      in regulation of kinase activity and in recruitment and activation of
      intracellular signaling pathways. Autophosphorylation is mediated by a sequential
      and precisely ordered intermolecular (trans) reaction. In this report we present
      structural and biochemical experiments demonstrating that formation of an
      asymmetric dimer between activated FGFR1 kinase domains is required for
      transphosphorylation of FGFR1 in FGF-stimulated cells. Transphosphorylation is
      mediated by specific asymmetric contacts between the N-lobe of one kinase
      molecule, which serves as an active enzyme, and specific docking sites on the C
      lobe of a second kinase molecule, which serves a substrate. Pathological loss-of
      function mutations or oncogenic activating mutations in this interface may hinder
      or facilitate asymmetric dimer formation and transphosphorylation, respectively.
      The experiments presented in this report provide the molecular basis underlying
      the control of transphosphorylation of FGF receptors and other receptor tyrosine
      kinases.

PMID- 20133754
TI  - Predicting the reaction coordinates of millisecond light-induced conformational
      changes in photoactive yellow protein.
AB  - Understanding the dynamics of large-scale conformational changes in proteins
      still poses a challenge for molecular simulations. We employ transition path
      sampling of explicit solvent molecular dynamics trajectories to obtain atomistic
      insight in the reaction network of the millisecond timescale partial unfolding
      transition in the photocycle of the bacterial sensor photoactive yellow protein.
      Likelihood maximization analysis predicts the best model for the reaction
      coordinates of each substep as well as tentative transition states, without
      further simulation. We find that the unfolding of the alpha-helical region 43-51
      is followed by sequential solvent exposure of both Glu46 and the chromophore.
      Which of these two residues is exposed first is correlated with the presence of a
      salt bridge that is part of the N-terminal domain. Additional molecular dynamics
      simulations indicate that the exposure of the chromophore does not result in a
      productive pathway. We discuss several possibilities for experimental validation
      of these predictions. Our results open the way for studying millisecond
      conformational changes in other medium-sized (signaling) proteins.

PMID- 20133755
TI  - General trend for pressurized superconducting hydrogen-dense materials.
AB  - The long-standing prediction that hydrogen can assume a metallic state under high
      pressure, combined with arguments put forward more recently that this state might
      even be superconducting up to high temperatures, continues to spur tremendous
      research activities toward the experimental realization of metallic hydrogen.
      These efforts have however so far been impeded by the enormous challenges
      associated with the exceedingly large required pressure. Hydrogen-dense
      materials, of the MH(4) form (where M can be, e.g., Si, Ge, or Sn) or of the
      MH(3) form (with M being, e.g., Al, Sc, Y, or La), allow for the rather exciting
      opportunity to carry out a proxy study of metallic hydrogen and associated high
      temperature superconductivity at pressures within the reach of current
      techniques. At least one experimental report indicates that a superconducting
      state might have been observed already in SiH(4), and several theoretical studies
      have predicted superconductivity in pressurized hydrogen-rich materials; however,
      no systematic dependence on the applied pressure has yet been identified so far.
      In the present work, we have used first-principles methods in an attempt to
      predict the superconducting critical temperature (T(c)) as a function of pressure
      (P) for three metal-hydride systems of the MH(3) form, namely ScH(3), YH(3), and
      LaH(3). By comparing the obtained results, we are able to point out a general
      trend in the T(c)-dependence on P. These gained insights presented here are
      likely to stimulate further theoretical studies of metallic phases of hydrogen
      dense materials and should lead to new experimental investigations of their
      superconducting properties.

PMID- 20133756
TI  - Reengineering orthogonally selective riboswitches.
AB  - The ability to independently control the expression of multiple genes by addition
      of distinct small-molecule modulators has many applications from synthetic
      biology, functional genomics, pharmaceutical target validation, through to gene
      therapy. Riboswitches are relatively simple, small-molecule-dependent, protein
      free, mRNA genetic switches that are attractive targets for reengineering in this
      context. Using a combination of chemical genetics and genetic selection, we have
      developed riboswitches that are selective for synthetic "nonnatural" small
      molecules and no longer respond to the natural intracellular ligands. The
      orthogonal selectivity of the riboswitches is also demonstrated in vitro using
      isothermal titration calorimetry and x-ray crystallography. The riboswitches
      allow highly responsive, dose-dependent, orthogonally selective, and dynamic
      control of gene expression in vivo. It is possible that this approach may be
      further developed to reengineer other natural riboswitches for application as
      small-molecule responsive genetic switches in both prokaryotes and eukaryotes.

PMID- 20133757
TI  - Engineering an artificial zymogen by alternate frame protein folding.
AB  - Alternate frame folding (AFF) is a novel mechanism by which allostery can be
      introduced into a protein where none may have existed previously. We employ this
      technology to convert the cytotoxic ribonuclease barnase into an artificial
      zymogen that is activated by HIV-1 protease. The AFF modification entails partial
      duplication of the polypeptide chain and mutation of a key catalytic residue in
      one of the duplicated segments. The resulting molecule can fold in one of two
      "frames" to yield the wild-type structure or a circularly permuted form in which
      the positions of the N- and C-termini are exchanged with a surface loop. It
      cannot take on both structures simultaneously because each competes for a shared
      amino acid sequence. An HIV-1 protease recognition sequence is inserted into one
      of the surface loops in the nonpermuted frame, and cleavage induces a shift from
      the nonpermuted fold to the permuted fold. Using the AFF mechanism, we were able
      to suppress k(cat)/K(M) by 250-fold in the proenzyme relative to wild-type
      barnase. HIV-1 protease cleavage subsequently increases k(cat)/K(M) by 130-fold.
      AFF is significant because it is general and can in principle be used to control
      activity of many enzymes, including those whose functions are not regulated by
      any existing mechanism.

PMID- 20133758
TI  - Human cytomegalovirus UL69 protein facilitates translation by associating with
      the mRNA cap-binding complex and excluding 4EBP1.
AB  - 4EBP1 is phosphorylated by the mTORC1 kinase. When mTORC1 activity is inhibited,
      hypophosphorylated 4EBP1 binds and sequesters eIF4E, a component of the mRNA cap
      binding complex, and blocks translation. As a consequence, mTORC1 activity is
      needed to maintain active translation. The human cytomegalovirus pUL38 protein
      preserves mTORC1 activity, keeping most of the E4BP1 in the infected cell in a
      hyperphosphorylated, inactive state. Here we report that a second viral protein,
      pUL69, also antagonizes the activity of 4EBP1, but by a separate mechanism. pUL69
      interacts directly with eIF4A1, an element of the cap-binding complex, and the
      poly(A)-binding protein, which binds to the complex. When pUL69 accumulates
      during infection with wild-type virus, 4EBP1 is excluded from the complex.
      However, 4EBP1 is present in the cap-binding complex after infection with a pUL69
      deficient virus, coincident with reduced accumulation of several late virus-coded
      proteins. We propose that pUL69 supports translation in human cytomegalovirus
      infected cells by excluding hypophosphorylated 4EBP1 from the cap-binding
      complex.

PMID- 20133759
TI  - HUNK suppresses metastasis of basal type breast cancers by disrupting the
      interaction between PP2A and cofilin-1.
AB  - Metastasis leads to the death of most cancer patients, and basal breast cancer is
      the most aggressive breast tumor type. Metastasis involves a complex cell
      migration process dependent on cytoskeletal remodeling such that targeting such
      remodeling in tumor cells could be clinically beneficial. Here we show that
      Hormonally Up-regulated Neu-associated Kinase (HUNK) is dramatically down
      regulated in tumor samples and cell lines derived from basal breast cancers.
      Reconstitution of HUNK expression in basal breast cancer cell lines blocked actin
      polymerization and reduced cell motility, resulting in decreased metastases in
      two in vivo murine cancer models. Mechanistically, HUNK overexpression sustained
      the constitutive phosphorylation and inactivation of cofilin-1 (CFL-1), thereby
      blocking the incorporation of new actin monomers into actin filaments. HUNK
      reconstitution in basal breast cancer cell lines prevented protein phosphatase 2
      A (PP2A), a phosphatase putatively acting on CFL-1, from binding to CFL-1. Our
      investigation of HUNK suggests that the interaction between PP2A and CFL-1 may be
      a target for antimetastasis therapy, particularly for basal breast cancers.

PMID- 20133760
TI  - Streamlined analysis schema for high-throughput identification of endogenous
      protein complexes.
AB  - Immunoprecipitation followed by mass spectrometry (IP/MS) has recently emerged as
      a preferred method in the analysis of protein complex components and cellular
      protein networks. Targeting endogenous protein complexes of higher eukaryotes,
      particularly in large-scale efforts, has been challenging due to cellular
      heterogeneity, high proteome complexity, and, compared to lower organisms, lack
      of efficient in-locus epitope-tagging techniques. It is further complicated by
      variability in nonspecific identifications and cross-reactivity of primary
      antibodies. Still, the study of endogenous human protein networks is highly
      desired despite its challenges. Here we describe a streamlined IP/MS protocol for
      the purification and identification of extended endogenous protein complexes. We
      investigate the sources of nonspecific protein binding and develop
      semiquantitative specificity filters that are based on peptide spectral count
      measurements. We also outline logical constraints for the derivation of accurate
      complex composition from IP/MS data and demonstrate the effectiveness of this
      approach by presenting our analyses of different transcriptional coregulator
      complexes. We show consistent purification of novel components for the Integrator
      complex, analyze the composition of the Mediator complex solely from our data to
      demonstrate the wide usability of spectral counts, and deconvolute heterogeneous
      HDAC1/2 networks into core complex modules and several novel subcomplex
      interactions.

PMID- 20133761
TI  - Discovery of a distinct domain in cyclin A sufficient for centrosomal
      localization independently of Cdk binding.
AB  - Centrosomes have recently emerged as key regulators of the cell cycle. The G1/S
      transition requires a functional centrosome, and centrosomal localization of
      numerous proteins, including cyclin/Cdk complexes, is important for the G2/M
      transition. Here we identify a modular centrosomal localization signal (CLS)
      localizing cyclin A to centrosomes independently of Cdk binding. The cyclin A CLS
      is located in a distinct part of the molecule compared with the cyclin E CLS and
      includes the MRAIL hydrophobic patch involved in substrate recognition. The
      cyclin A CLS interacts with p27(KIP1), and expression of p27(KIP1) removes cyclin
      A but not cyclin E from centrosomes. Expression of the cyclin A CLS displaces
      both endogenous cyclin A and E from centrosomes and inhibits DNA replication,
      supporting an emerging concept that DNA replication is linked to centrosomal
      events. Structural analysis indicates that differences in surface charge and
      length of the C-terminal helix explain why the MRAIL region in cyclin E is not a
      functional CLS. These results indicate that the cyclin A CLS may contribute to
      targeting and recognition of centrosomal Cdk substrates and is required for
      specific effects of p27(KIP1) on cyclin A-Cdk2.

PMID- 20133762
TI  - Cross-frequency coupling supports multi-item working memory in the human
      hippocampus.
AB  - Recent findings indicate that the hippocampus supports not only long-term memory
      encoding but also plays a role in working memory (WM) maintenance of multiple
      items; however, the neural mechanism underlying multi-item maintenance is still
      unclear. Theoretical work suggests that multiple items are being maintained by
      neural assemblies synchronized in the gamma frequency range (25-100 Hz) that are
      locked to consecutive phase ranges of oscillatory activity in the theta frequency
      range (4-8 Hz). Indeed, cross-frequency coupling of the amplitude of high
      frequency activity to the phase of slower oscillations has been described both in
      animals and in humans, but has never been linked to a theoretical model of a
      cognitive process. Here we used intracranial EEG recordings in human epilepsy
      patients to test pivotal predictions from theoretical work. First, we show that
      simultaneous maintenance of multiple items in WM is accompanied by cross
      frequency coupling of oscillatory activity in the hippocampus, which is recruited
      during multi-item WM. Second, maintenance of an increasing number of items is
      associated with modulation of beta/gamma amplitude with theta band activity of
      lower frequency, consistent with the idea that longer cycles are required for an
      increased number of representations by gamma cycles. This effect cannot be
      explained by a difference in theta or beta/gamma power. Third, we describe how
      the precision of cross-frequency coupling predicts individual WM performance.
      These data support the idea that working memory in humans depends on a neural
      code using phase information.

PMID- 20133763
TI  - NleH effectors interact with Bax inhibitor-1 to block apoptosis during
      enteropathogenic Escherichia coli infection.
AB  - The human pathogens enteropathogenic (EPEC) and enterohemorrhagic Escherichia
      coli and the related mouse pathogen Citrobacter rodentium subvert a variety of
      host cell signaling pathways via their plethora of type III secreted effectors,
      including triggering of an early apoptotic response. EPEC-infected cells do not
      develop late apoptotic symptoms, however. In this study we demonstrate that the
      NleH family effectors, homologs of the Shigella effector kinase OspG, blocks
      apoptosis. During EPEC infection, NleH effectors inhibit elevation of cytosolic
      Ca(2+) concentrations, nuclear condensation, caspase-3 activation, and membrane
      blebbing and promote cell survival. NleH1 alone is sufficient to prevent
      procaspase-3 cleavage induced by the proapoptotic compounds staurosporine,
      brefeldin A, and tunicamycin. Using C. rodentium, we found that NleH inhibits
      procaspase-3 cleavage at the bacterial attachment sites in vivo. A yeast two
      hybrid screen identified the endoplasmic reticulum six-transmembrane protein Bax
      inhibitor-1 (BI-1) as an NleH-interacting partner. We mapped the NleH-binding
      site to the N-terminal 40 amino acids of BI-1. Knockdown of BI-1 resulted in the
      loss of NleH's antiapoptotic activity. These results indicate that NleH effectors
      are inhibitors of apoptosis that may act through BI-1 to carry out their
      cytoprotective function.

PMID- 20133764
TI  - Nasal chemosensory cells use bitter taste signaling to detect irritants and
      bacterial signals.
AB  - The upper respiratory tract is continually assaulted with harmful dusts and
      xenobiotics carried on the incoming airstream. Detection of such irritants by the
      trigeminal nerve evokes protective reflexes, including sneezing, apnea, and local
      neurogenic inflammation of the mucosa. Although free intra-epithelial nerve
      endings can detect certain lipophilic irritants (e.g., mints, ammonia), the
      epithelium also houses a population of trigeminally innervated solitary
      chemosensory cells (SCCs) that express T2R bitter taste receptors along with
      their downstream signaling components. These SCCs have been postulated to enhance
      the chemoresponsive capabilities of the trigeminal irritant-detection system.
      Here we show that transduction by the intranasal solitary chemosensory cells is
      necessary to evoke trigeminally mediated reflex reactions to some irritants
      including acyl-homoserine lactone bacterial quorum-sensing molecules, which
      activate the downstream signaling effectors associated with bitter taste
      transduction. Isolated nasal chemosensory cells respond to the classic bitter
      ligand denatonium as well as to the bacterial signals by increasing intracellular
      Ca(2+). Furthermore, these same substances evoke changes in respiration
      indicative of trigeminal activation. Genetic ablation of either G alpha-gustducin
      or TrpM5, essential elements of the T2R transduction cascade, eliminates the
      trigeminal response. Because acyl-homoserine lactones serve as quorum-sensing
      molecules for gram-negative pathogenic bacteria, detection of these substances by
      airway chemoreceptors offers a means by which the airway epithelium may trigger
      an epithelial inflammatory response before the bacteria reach population
      densities capable of forming destructive biofilms.

PMID- 20133765
TI  - ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and
      ameliorates amyloid pathology in mice with AD.
AB  - Cholesterol metabolism has been implicated in the pathogenesis of several
      neurodegenerative diseases, including the abnormal accumulation of amyloid-beta,
      one of the pathological hallmarks of Alzheimer disease (AD). Acyl-CoA:cholesterol
      acyltransferases (ACAT1 and ACAT2) are two enzymes that convert free cholesterol
      to cholesteryl esters. ACAT inhibitors have recently emerged as promising drug
      candidates for AD therapy. However, how ACAT inhibitors act in the brain has so
      far remained unclear. Here we show that ACAT1 is the major functional isoenzyme
      in the mouse brain. ACAT1 gene ablation (A1-) in triple transgenic (i.e., 3XTg
      AD) mice leads to more than 60% reduction in full-length human APPswe as well as
      its proteolytic fragments, and ameliorates cognitive deficits. At 4 months of
      age, A1- causes a 32% content increase in 24-hydroxycholesterol (24SOH), the
      major oxysterol in the brain. It also causes a 65% protein content decrease in
      HMG-CoA reductase (HMGR) and a 28% decrease in sterol synthesis rate in AD mouse
      brains. In hippocampal neurons, A1- causes an increase in the 24SOH synthesis
      rate; treating hippocampal neuronal cells with 24SOH causes rapid declines in
      hAPP and in HMGR protein levels. A model is provided to explain our findings: in
      neurons, A1- causes increases in cholesterol and 24SOH contents in the
      endoplasmic reticulum, which cause reductions in hAPP and HMGR protein contents
      and lead to amelioration of amyloid pathology. Our study supports the potential
      of ACAT1 as a therapeutic target for treating certain forms of AD.

PMID- 20133766
TI  - Aspartate racemase, generating neuronal D-aspartate, regulates adult
      neurogenesis.
AB  - D-aspartic acid is abundant in the developing brain. We have identified and
      cloned mammalian aspartate racemase (DR), which converts L-aspartate to D
      aspartate and colocalizes with D-aspartate in the brain and neuroendocrine
      tissues. Depletion of DR by retrovirus-mediated expression of short-hairpin RNA
      in newborn neurons of the adult hippocampus elicits profound defects in the
      dendritic development and survival of newborn neurons and survival. Because D
      aspartate is a potential endogenous ligand for NMDA receptors, the loss of which
      elicits a phenotype resembling DR depletion, D-aspartate may function as a
      modulator of adult neurogenesis.

PMID- 20133767
TI  - A Drosophila model for TDP-43 proteinopathy.
AB  - Neuropathology involving TAR DNA binding protein-43 (TDP-43) has been identified
      in a wide spectrum of neurodegenerative diseases collectively named as TDP-43
      proteinopathy, including amyotrophic lateral sclerosis (ALS) and frontotemporal
      lobar dementia (FTLD). To test whether increased expression of wide-type human
      TDP-43 (hTDP-43) may cause neurotoxicity in vivo, we generated transgenic flies
      expressing hTDP-43 in various neuronal subpopulations. Expression in the fly eyes
      of the full-length hTDP-43, but not a mutant lacking its amino-terminal domain,
      led to progressive loss of ommatidia with remarkable signs of neurodegeneration.
      Expressing hTDP-43 in mushroom bodies (MBs) resulted in dramatic axon losses and
      neuronal death. Furthermore, hTDP-43 expression in motor neurons led to axon
      swelling, reduction in axon branches and bouton numbers, and motor neuron loss
      together with functional deficits. Thus, our transgenic flies expressing hTDP-43
      recapitulate important neuropathological and clinical features of human TDP-43
      proteinopathy, providing a powerful animal model for this group of devastating
      diseases. Our study indicates that simply increasing hTDP-43 expression is
      sufficient to cause neurotoxicity in vivo, suggesting that aberrant regulation of
      TDP-43 expression or decreased clearance of hTDP-43 may contribute to the
      pathogenesis of TDP-43 proteinopathy.

PMID- 20133768
TI  - Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and
      depressive behavior.
AB  - Proinflammatory cytokines, such as IL-1beta, have been implicated in the cellular
      and behavioral effects of stress and in mood disorders, although the downstream
      signaling pathways underlying these effects have not been determined. In the
      present study, we demonstrate a critical role for NF-kappaB signaling in the
      actions of IL-1beta and stress. Stress inhibition of neurogenesis in the adult
      hippocampus, which has been implicated in the prodepressive effects of stress, is
      blocked by administration of an inhibitor of NF-kappaB. Further analysis reveals
      that stress activates NF-kappaB signaling and decreases proliferation of neural
      stem-like cells but not early neural progenitor cells in the adult hippocampus.
      We also find that depressive-like behaviors caused by exposure to chronic stress
      are mediated by NF-kappaB signaling. Together, these data identify NF-kappaB
      signaling as a critical mediator of the antineurogenic and behavioral actions of
      stress and suggest previously undescribed therapeutical targets for depression.

PMID- 20133769
TI  - Universal distribution of protein evolution rates as a consequence of protein
      folding physics.
AB  - The hypothesis that folding robustness is the primary determinant of the
      evolution rate of proteins is explored using a coarse-grained off-lattice model.
      The simplicity of the model allows rapid computation of the folding probability
      of a sequence to any folded conformation. For each robust folder, the network of
      sequences that share its native structure is identified. The fitness of a
      sequence is postulated to be a simple function of the number of misfolded
      molecules that have to be produced to reach a characteristic protein abundance.
      After fixation probabilities of mutants are computed under a simple population
      dynamics model, a Markov chain on the fold network is constructed, and the fold
      averaged evolution rate is computed. The distribution of the logarithm of the
      evolution rates across distinct networks exhibits a peak with a long tail on the
      low rate side and resembles the universal empirical distribution of the
      evolutionary rates more closely than either distribution resembles the log-normal
      distribution. The results suggest that the universal distribution of the
      evolutionary rates of protein-coding genes is a direct consequence of the basic
      physics of protein folding.

PMID- 20133770
TI  - Kappa opioid receptor contributes to EGF-stimulated neurite extension in
      development.
AB  - Epidermal growth factor (EGF), a mitogen, also stimulates neurite extension
      during development, but the underlying mechanism is elusive. This study reveals a
      functional role for kappa opioid receptor (KOR) in EGF-stimulated neurite
      extension, and the underlying mechanism. EGF and activated EGF receptor (EGFR)
      levels are elevated in embryonic spinal cords during late gestation stages, with
      concurrent rise in protein levels of KOR and axon extension markers, growth
      associated protein 43 (GAP43), and transient axonal glycoprotein-1 (TAG-1). Both
      GAP43 and TAG-1 levels are significantly lower in KOR-null (KOR(-/-)) spinal
      cords, and EGFR inhibitors effectively reduce the levels of KOR, GAP43, and TAG-1
      in wild-type embryonic spinal cords. For KOR(-/-) or KOR-knockdown dorsal root
      ganglion (DRG) neurons, EGF can no longer effectively stimulate axon extension,
      which can be rescued by introducing a constitutive KOR expressing vector but not
      by a regulated KOR vector carrying its 5' untranslated region, which can be bound
      and repressed by growth factor receptor-bound protein 7 (Grb7). Furthermore,
      blocking KOR activation by application of anti-dynorphin, KOR antagonist, or EGFR
      inhibitor effectively reduces axon extension of DRG neurons. Thus, EGF-stimulated
      axon extension during development is mediated, at least partially, by specific
      elevation of KOR protein production at posttranscriptional level, as well as
      activation of KOR signaling. The result also reveals an action of EGF to augment
      posttranscriptional regulation of certain mRNAs during developmental stages.

PMID- 20133771
TI  - Hsp90 inhibitors block outgrowth of EBV-infected malignant cells in vitro and in
      vivo through an EBNA1-dependent mechanism.
AB  - EBV causes infectious mononucleosis and is associated with certain malignancies.
      EBV nuclear antigen 1 (EBNA1) mediates EBV genome replication, partition, and
      transcription, and is essential for persistence of the viral genome in host
      cells. Here we demonstrate that Hsp90 inhibitors decrease EBNA1 expression and
      translation, and that this effect requires the Gly-Ala repeat domain of EBNA1.
      Hsp90 inhibitors induce the death of established, EBV-transformed lymphoblastoid
      cell lines at doses nontoxic to normal cells, and this effect is substantially
      reversed when lymphoblastoid cell lines are stably infected with a retrovirus
      expressing a functional EBNA1 mutant lacking the Gly-Ala repeats. Hsp90
      inhibitors prevent EBV transformation of primary B cells, and strongly inhibit
      the growth of EBV-induced lymphoproliferative disease in SCID mice. These results
      suggest that Hsp90 inhibitors may be particularly effective for treating EBV
      induced diseases requiring the continued presence of the viral genome.

PMID- 20133772
TI  - Peptide vaccines prevent tumor growth by activating T cells that respond to
      native tumor antigens.
AB  - Peptide vaccines enhance the response of T cells toward tumor antigens and
      represent a strategy to augment antigen-independent immunotherapies of cancer.
      However, peptide vaccines that include native tumor antigens rarely prevent tumor
      growth. We have assembled a set of peptide variants for a mouse-colon tumor model
      to determine how to improve T-cell responses. These peptides have similar
      affinity for MHC molecules, but differ in the affinity of the peptide-MHC/T-cell
      receptor interaction with a tumor-specific T-cell clone. We systematically
      demonstrated that effective antitumor responses are generated after vaccination
      with variant peptides that stimulate the largest proportion of endogenous T cells
      specific for the native tumor antigen. Importantly, we found some variant
      peptides that strongly stimulated a specific T-cell clone in vitro, but elicited
      fewer tumor-specific T cells in vivo, and were not protective. The T cells
      expanded by the effective vaccines responded to the wild-type antigen by making
      cytokines and killing target cells, whereas most of the T cells expanded by the
      ineffective vaccines only responded to the peptide variants. We conclude that
      peptide-variant vaccines are most effective when the peptides react with a large
      responsive part of the tumor-specific T-cell repertoire.

PMID- 20133773
TI  - Electron traps and their effect on the surface chemistry of TiO2(110).
AB  - Oxygen vacancies on metal oxide surfaces have long been thought to play a key
      role in the surface chemistry. Such processes have been directly visualized in
      the case of the model photocatalyst surface TiO(2)(110) in reactions with water
      and molecular oxygen. These vacancies have been assumed to be neutral in
      calculations of the surface properties. However, by comparing experimental and
      simulated scanning tunneling microscopy images and spectra, we show that oxygen
      vacancies act as trapping centers and are negatively charged. We demonstrate that
      charging the defect significantly affects the reactivity by following the
      reaction of molecular oxygen with surface hydroxyl formed by water dissociation
      at the vacancies. Calculations with electronically charged hydroxyl favor a
      condensation reaction forming water and surface oxygen adatoms, in line with
      experimental observations. This contrasts with simulations using neutral hydroxyl
      where hydrogen peroxide is found to be the most stable product.

PMID- 20133774
TI  - The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the
      contactin family of neural recognition molecules.
AB  - The receptor protein tyrosine phosphatases gamma (PTPRG) and zeta (PTPRZ) are
      expressed primarily in the nervous system and mediate cell adhesion and signaling
      events during development. We report here the crystal structures of the carbonic
      anhydrase-like domains of PTPRZ and PTPRG and show that these domains interact
      directly with the second and third immunoglobulin repeats of the members of the
      contactin (CNTN) family of neural recognition molecules. Interestingly, these
      receptors exhibit distinct specificities: PTPRZ binds only to CNTN1, whereas
      PTPRG interacts with CNTN3, 4, 5, and 6. Furthermore, we present crystal
      structures of the four N-terminal immunoglobulin repeats of mouse CNTN4 both
      alone and in complex with the carbonic anhydrase-like domain of mouse PTPRG. In
      these structures, the N-terminal region of CNTN4 adopts a horseshoe-like
      conformation found also in CNTN2 and most likely in all CNTNs. This restrained
      conformation of the second and third immunoglobulin domains creates a binding
      site that is conserved among CNTN3, 4, 5, and 6. This site contacts a discrete
      region of PTPRG composed primarily of an extended beta-hairpin loop found in both
      PTPRG and PTPRZ. Overall, these findings implicate PTPRG, PTPRZ and CNTNs as a
      group of receptors and ligands involved in the manifold recognition events that
      underlie the construction of neural networks.

PMID- 20133776
TI  - Synthetic design of strong promoters.
AB  - We have taken a synthetic biology approach to the generation and screening of
      transcription factor binding sites for activity in human cells. All possible 10
      mer DNA sequences were printed on microarrays as 100-mers containing 10 repeats
      of the same sequence in tandem, yielding an oligonucleotide library of 52,429
      unique sequences. This library of potential enhancers was introduced into a
      retroviral vector and screened in multiple cell lines for the ability to activate
      GFP transcription from a minimal CMV promoter. With this method, we isolated 100
      bp synthetic enhancer elements that were as potent at activating transcription as
      the WT CMV immediate early enhancer. The activity of the recovered elements was
      strongly dependent on the cell line in which they were recovered. None of the
      elements were capable of achieving the same levels of transcriptional enhancement
      across all tested cell lines as the CMV enhancer. A second screen, for enhancers
      capable of synergizing with the elements from the original screen, yielded
      compound enhancers that were capable of twofold greater enhancement activity than
      the CMV enhancer, with higher levels of activity than the original synthetic
      enhancer across multiple cell lines. These findings suggest that the 10-mer
      synthetic enhancer space is sufficiently rich to allow the creation of synthetic
      promoters of all strengths in most, if not all, cell types.

PMID- 20133777
TI  - Identification and functional characterization of paxillin as a target of protein
      tyrosine phosphatase receptor T.
AB  - Protein tyrosine phosphatase receptor-type T (PTPRT) is the most frequently
      mutated tyrosine phosphatase in human cancers. However, the cell signaling
      pathways regulated by PTPRT largely remain to be elucidated. Here, we show that
      paxillin is a direct substrate of PTPRT and that PTPRT specifically regulates
      paxillin phosphorylation at tyrosine residue 88 (Y88) in colorectal cancer (CRC)
      cells. We engineered CRC cells homozygous for a paxillin Y88F knock-in mutant and
      found that these cells exhibit significantly reduced cell migration and impaired
      anchorage-independent growth, fail to form xenograft tumors in nude mice, and
      have decreased phosphorylation of p130CAS, SHP2, and AKT. PTPRT knockout mice
      that we generated exhibit increased levels of colonic paxillin phosphorylation at
      residue Y88 and are highly susceptible to carcinogen azoxymethane-induced colon
      tumor, providing critical in vivo evidence that PTPRT normally functions as a
      tumor suppressor. Moreover, similarly increased paxillin pY88 is also found as a
      common feature of human colon cancers. These studies reveal an important
      signaling pathway that plays a critical role in colorectal tumorigenesis.

PMID- 20133778
TI  - Molecular keys of the tropism of integration of the cholera toxin phage.
AB  - Cholera toxin is encoded in the genome of CTXvarphi, a lysogenic filamentous
      phage of Vibrio cholerae. CTXvarphi variants contribute to the genetic diversity
      of cholera epidemic strains. It has been shown that the El Tor variant of
      CTXvarphi hijacks XerC and XerD, two host-encoded tyrosine recombinases that
      normally function to resolve chromosome dimers, to integrate at dif1, the dimer
      resolution site of the larger of the two V. cholerae chromosomes. However, the
      exact mechanism of integration of CTXvarphi and the rules governing its
      integration remained puzzling, with phage variants integrated at either or both
      dimer resolution sites of the two V. cholerae chromosomes. We designed a genetic
      system to determine experimentally the tropism of integration of CTXvarphi and
      thus define rules of compatibility between phage variants and dimer resolution
      sites. We then showed in vitro how these rules are explained by the direct
      integration of the single-stranded phage genome into the double-stranded
      bacterial genome. Finally, we showed how the evolution of phage attachment and
      chromosome dimer resolution sites contributes to the generation of genetic
      diversity among cholera epidemic strains.

PMID- 20133779
TI  - Genetic contribution to individual variation in binocular rivalry rate.
AB  - Binocular rivalry occurs when conflicting images are presented in corresponding
      locations of the two eyes. Perception alternates between the images at a rate
      that is relatively stable within individuals but that varies widely between
      individuals. The determinants of this variation are unknown. In addition, slow
      binocular rivalry has been demonstrated in bipolar disorder, a psychiatric
      condition with high heritability. The present study therefore examined whether
      there is a genetic contribution to individual variation in binocular rivalry
      rate. We employed the twin method and studied both monozygotic (MZ) twins (n =
      128 pairs) who are genetically identical, and dizygotic (DZ) twins (n = 220
      pairs) who share roughly half their genes. MZ and DZ twin correlations for
      binocular rivalry rate were 0.51 and 0.19, respectively. The best-fitting genetic
      model showed 52% of the variance in binocular rivalry rate was accounted for by
      additive genetic factors. In contrast, nonshared environmental influences
      accounted for 18% of the variance, with the remainder attributed to measurement
      error. This study therefore demonstrates a substantial genetic contribution to
      individual variation in binocular rivalry rate. The results support the vigorous
      pursuit of genetic and molecular studies of binocular rivalry and further
      characterization of slow binocular rivalry as an endophenotype for bipolar
      disorder.

PMID- 20133780
TI  - Coherent concepts are computed in the anterior temporal lobes.
AB  - In his Philosophical Investigations, Wittgenstein famously noted that the
      formation of semantic representations requires more than a simple combination of
      verbal and nonverbal features to generate conceptually based similarities and
      differences. Classical and contemporary neuroscience has tended to focus upon how
      different neocortical regions contribute to conceptualization through the
      summation of modality-specific information. The additional yet critical step of
      computing coherent concepts has received little attention. Some computational
      models of semantic memory are able to generate such concepts by the addition of
      modality-invariant information coded in a multidimensional semantic space. By
      studying patients with semantic dementia, we demonstrate that this aspect of
      semantic memory becomes compromised following atrophy of the anterior temporal
      lobes and, as a result, the patients become increasingly influenced by
      superficial rather than conceptual similarities.

PMID- 20133781
TI  - Synergistic antitumor effects of combined cathepsin B and cathepsin Z
      deficiencies on breast cancer progression and metastasis in mice.
AB  - The lysosomal cysteine proteases cathepsin B (Ctsb) and cathepsin Z (Ctsz, also
      called cathepsin X/P) have been implicated in cancer pathogenesis. Compensation
      of Ctsb by Ctsz in Ctsb (-/-) mice has been suggested. To further define the
      functional interplay of these proteases in the context of cancer, we generated
      Ctsz null mice, crossed them with Ctsb-deficient mice harboring a transgene for
      the mammary duct-specific expression of polyoma middle T oncogene (PymT), and
      analyzed the effects of single and combined Ctsb and Ctsz deficiencies on breast
      cancer progression. Single Ctsb deficiency resulted in delayed detection of first
      tumors and reduced tumor burden, whereas Ctsz-deficient mice had only a prolonged
      tumor-free period. However, only a trend toward reduced metastatic burden without
      statistical significance was detected in both single mutants. Strikingly,
      combined loss of Ctsb and Ctsz led to additive effects, resulting in significant
      and prominent delay of early and advanced tumor development, improved
      histopathologic tumor grading, as well as a 70% reduction in the number of lung
      metastases and an 80% reduction in the size of these metastases. We conclude that
      the double deficiency of Ctsb and Ctsz exerts significant synergistic anticancer
      effects, whereas the single deficiencies demonstrate at least partial reciprocal
      compensation.

PMID- 20133782
TI  - Mutant EGFR is required for maintenance of glioma growth in vivo, and its
      ablation leads to escape from receptor dependence.
AB  - Epidermal growth factor receptor (EGFR) gene amplification is the most common
      genetic alteration in high-grade glioma, and approximately 50% of EGFR-amplified
      tumors also harbor a constitutively active mutant form of the receptor,
      DeltaEGFR. Although DeltaEGFR greatly enhances tumor growth and is thus an
      attractive target for anti-glioma therapies, recent clinical experiences with
      EGFR kinase inhibitors have been disappointing, because resistance is common and
      tumors eventually recur. Interestingly, it has not been established whether
      DeltaEGFR is required for maintenance of glioma growth in vivo, and, by
      extension, if it truly represents a rational therapeutic target. Here, we
      demonstrate that in vivo silencing of regulatable DeltaEGFR with doxycycline
      attenuates glioma growth and, therefore, that it is crucial for maintenance of
      enhanced tumorigenicity. Similar to the clinical experience, tumors eventually
      regained aggressive growth after a period of stasis, but interestingly, without
      re-expression of DeltaEGFR. To determine how tumors acquired this ability, we
      found that a unique gene, KLHDC8, herein referred to as SDeltaE (Substitute for
      DeltaEGFR Expression)-1, is highly expressed in these tumors, which have escaped
      dependence on DeltaEGFR. SDeltaE-1 is also expressed in human gliomas and
      knockdown of its expression in DeltaEGFR-independent "escaper" tumors suppressed
      tumor growth. Taken together, we conclude that DeltaEGFR is required for both
      glioma establishment and maintenance, and that gliomas undergo selective pressure
      in vivo to employ alternative compensatory pathways to maintain aggressiveness in
      the event of EGFR silencing. Such alternative pathways function as substitutes
      for DeltaEGFR signaling and should therefore be considered as potential targets
      for additional therapy.

PMID- 20133783
TI  - Setdb2 restricts dorsal organizer territory and regulates left-right asymmetry
      through suppressing fgf8 activity.
AB  - Dorsal organizer formation is one of the most critical steps in early embryonic
      development. Several genes and signaling pathways that positively regulate the
      dorsal organizer development have been identified; however, little is known about
      the factor(s) that negatively regulates the organizer formation. Here, we show
      that Setdb2, a SET domain-containing protein possessing potential histone H3K9
      methyltransferase activity, restricts dorsal organizer development and regulates
      left-right asymmetry by suppressing fibroblast growth factor 8 (fgf8) expression.
      Knockdown of Setdb2 results in a massive expansion of dorsal organizer markers
      floating head (flh), goosecoid (gsc), and chordin (chd), as well as a significant
      increase of fgf8, but not fgf4 mRNAs. Consequently, disrupted midline patterning
      and resultant randomization of left-right asymmetry are observed in Setdb2
      deficient embryos. These characteristic changes induced by Setdb2 deficiency can
      be nearly corrected by either overexpression of a dominant-negative fgf receptor
      or knockdown of fgf8, suggesting an essential role for Setdb2-Fgf8 signaling in
      restricting dorsal organizer territory and regulating left-right asymmetry. These
      results provide unique evidence that a SET domain-containing protein potentially
      involved in the epigenetic control negatively regulates dorsal organizer
      formation during early embryonic development.

PMID- 20133784
TI  - Cardioprotective effects of growth hormone-releasing hormone agonist after
      myocardial infarction.
AB  - Whether the growth hormone (GH)/insulin-like growth factor 1(IGF-1) axis exerts
      cardioprotective effects remains controversial; and the underlying mechanism(s)
      for such actions are unclear. Here we tested the hypothesis that growth hormone
      releasing hormone (GHRH) directly activates cellular reparative mechanisms within
      the injured heart, in a GH/IGF-1 independent fashion. After experimental
      myocardial infarction (MI), rats were randomly assigned to receive, during a 4
      week period, either placebo (n = 14), rat recombinant GH (n = 8) or JI-38 (n = 8;
      50 microg/kg per day), a potent GHRH agonist. JI-38 did not elevate serum levels
      of GH or IGF-1, but it markedly attenuated the degree of cardiac functional
      decline and remodeling after injury. In contrast, GH administration markedly
      elevated body weight, heart weight, and circulating GH and IGF-1, but it did not
      offset the decline in cardiac structure and function. Whereas both JI-38 and GH
      augmented levels of cardiac precursor cell proliferation, only JI-38 increased
      antiapoptotic gene expression. The receptor for GHRH was detectable on myocytes,
      supporting direct activation of cardiac signal transduction. Collectively, these
      findings demonstrate that within the heart, GHRH agonists can activate cardiac
      repair after MI, suggesting the existence of a potential signaling pathway based
      on GHRH in the heart. The phenotypic profile of the response to a potent GHRH
      agonist has therapeutic implications.

PMID- 20133785
TI  - Arabidopsis synaptotagmin SYTA regulates endocytosis and virus movement protein
      cell-to-cell transport.
AB  - Synaptotagmins are calcium sensors that regulate synaptic vesicle
      exo/endocytosis. Thought to be exclusive to animals, they have recently been
      characterized in plants. We show that Arabidopsis synaptotagmin SYTA regulates
      endosome recycling and movement protein (MP)-mediated trafficking of plant virus
      genomes through plasmodesmata. SYTA localizes to endosomes in plant cells and
      directly binds the distinct Cabbage leaf curl virus (CaLCuV) and Tobacco mosaic
      virus (TMV) cell-to-cell movement proteins. In a SYTA knockdown line, CaLCuV
      systemic infection is delayed, and cell-to-cell spread of TMV and CaLCuV movement
      proteins is inhibited. A dominant-negative SYTA mutant causes depletion of plasma
      membrane-derived endosomes, produces large intracellular vesicles attached to
      plasma membrane, and inhibits cell-to-cell trafficking of TMV and CaLCuV movement
      proteins, when tested in an Agrobacterium-based leaf expression assay. Our
      studies show that SYTA regulates endocytosis, and suggest that distinct virus
      movement proteins transport their cargos to plasmodesmata for cell-to-cell spread
      via an endocytic recycling pathway.

PMID- 20133786
TI  - The circadian output gene takeout is regulated by Pdp1epsilon.
AB  - The circadian clock controls many circadian outputs. Although a large number of
      transcripts are affected by the circadian oscillator, very little is known about
      their regulation and function. We show here that the Drosophila takeout gene, one
      of the output genes of the circadian oscillator, is regulated similarly to the
      circadian clock genes Clock (Clk) and cry. takeout RNA levels are at constant
      high levels in Clk(JRK) mutants. The circadian transcription factor PAR domain
      protein 1 (Pdp1epsilon) is a transcription factor that had previously been
      postulated to control clock output genes, particularly genes regulated similarly
      to Clk. In agreement with this, we show here that Pdp1epsilon is a regulator of
      takeout. Takeout levels are low in flies with reduced Pdp1epsilon and high in
      flies with increased amounts of Pdp1epsilon. Furthermore, flies with reduced or
      elevated Pdp1epsilon levels in the fat body display courtship defects,
      identifying Pdp1epsilon as an important transcriptional regulator in that tissue.

PMID- 20133787
TI  - Analysis of the cellular mechanism underlying inhibition of EAE after treatment
      with anti-NKG2A F(ab')2.
AB  - Autoimmune encephalomyelitis may be ameliorated experimentally by enhancing NK
      cell-mediated elimination of activated autoreactive T cells through a mutation
      that interrupts the interaction between Qa-1(b) and CD94/NKG2A. Here we evaluate
      the ability of an anti-NKG2A F(ab')(2) Ab to enhance elimination of autoreactive
      T cells and reduce experimental autoimmune encephalomyelitis (EAE). Anti-NKG2A
      F(ab')(2) treatment diminishes progression of both myelin oligodendrocyte
      glycoprotein (MOG)-induced EAE in intact C57BL/6 mice and after adoptive transfer
      of disease-causing T cells. Analyses of the underlying mechanism revealed that
      administration of anti-NKG2A F(ab')(2) Ab reduces CD4(+) T recall responses to
      MOG and skews the proportion of IL-17- and IFNgamma-producing CD4(+) T cells
      toward the protective IL-4- and IL-10-secreting CD4(+) T cell subpopulations.
      CD94/NKG2A-dependent inhibition of inflammatory damage to spinal cord is
      associated with decreased infiltration of T cells and reduced microglia
      activation in the central nervous system. Because anti-NKG2A F(ab')(2) treatment
      had no detectable effect on the numbers or activity of T and B lymphocytes and NK
      cells in peripheral lymphoid tissues, this anti-NKG2A-based approach may
      represent a safe and effective therapy for this CNS disorder.

PMID- 20133788
TI  - Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1
      DNA replication components.
AB  - The cellular transcriptional coactivator HCF-1 interacts with numerous
      transcription factors as well as other coactivators and is a component of
      multiple chromatin modulation complexes. The protein is essential for the
      expression of the immediate early genes of both herpes simplex virus (HSV) and
      varicella zoster virus and functions, in part, by coupling chromatin modification
      components including the Set1 or MLL1 histone methyltransferases and the histone
      demethylase LSD1 to promote the installation of positive chromatin marks and the
      activation of viral immediately early gene transcription. Although studies have
      investigated the role of HCF-1 in both cellular and viral transcription, little
      is known about other processes that the protein may be involved in. Here we
      demonstrate that HCF-1 localizes to sites of HSV replication late in infection.
      HCF-1 interacts directly and simultaneously with both HSV DNA replication
      proteins and the cellular histone chaperone Asf1b, a protein that regulates the
      progression of cellular DNA replication forks via chromatin reorganization. Asf1b
      localizes with HCF-1 in viral replication foci and depletion of Asf1b results in
      significantly reduced viral DNA accumulation. The results support a model in
      which the transcriptional coactivator HCF-1 is a component of the HSV DNA
      replication assembly and promotes viral DNA replication by coupling Asf1b to DNA
      replication components. This coupling provides a novel function for HCF-1 and
      insights into the mechanisms of modulating chromatin during DNA replication.

PMID- 20133789
TI  - Structure of the Plasmodium falciparum M17 aminopeptidase and significance for
      the design of drugs targeting the neutral exopeptidases.
AB  - Current therapeutics and prophylactics for malaria are under severe challenge as
      a result of the rapid emergence of drug-resistant parasites. The human malaria
      parasite Plasmodium falciparum expresses two neutral aminopeptidases, PfA-M1 and
      PfA-M17, which function in regulating the intracellular pool of amino acids
      required for growth and development inside the red blood cell. These enzymes are
      essential for parasite viability and are validated therapeutic targets. We
      previously reported the X-ray crystal structure of the monomeric PfA-M1 and
      proposed a mechanism for substrate entry and free amino acid release from the
      active site. Here, we present the X-ray crystal structure of the hexameric
      leucine aminopeptidase, PfA-M17, alone and in complex with two inhibitors with
      antimalarial activity. The six active sites of the PfA-M17 hexamer are arranged
      in a disc-like fashion so that they are orientated inwards to form a central
      catalytic cavity; flexible loops that sit at each of the six entrances to the
      catalytic cavern function to regulate substrate access. In stark contrast to PfA
      M1, PfA-M17 has a narrow and hydrophobic primary specificity pocket which
      accounts for its highly restricted substrate specificity. We also explicate the
      essential roles for the metal-binding centers in these enzymes (two in PfA-M17
      and one in PfA-M1) in both substrate and drug binding. Our detailed understanding
      of the PfA-M1 and PfA-M17 active sites now permits a rational approach in the
      development of a unique class of two-target and/or combination antimalarial
      therapy.

PMID- 20133790
TI  - Cross-cultural recognition of basic emotions through nonverbal emotional
      vocalizations.
AB  - Emotional signals are crucial for sharing important information, with
      conspecifics, for example, to warn humans of danger. Humans use a range of
      different cues to communicate to others how they feel, including facial, vocal,
      and gestural signals. We examined the recognition of nonverbal emotional
      vocalizations, such as screams and laughs, across two dramatically different
      cultural groups. Western participants were compared to individuals from remote,
      culturally isolated Namibian villages. Vocalizations communicating the so-called
      "basic emotions" (anger, disgust, fear, joy, sadness, and surprise) were
      bidirectionally recognized. In contrast, a set of additional emotions was only
      recognized within, but not across, cultural boundaries. Our findings indicate
      that a number of primarily negative emotions have vocalizations that can be
      recognized across cultures, while most positive emotions are communicated with
      culture-specific signals.

PMID- 20133791
TI  - Evidence for a functional role of IgE anticitrullinated protein antibodies in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease involving inflammation
      of the joints. Among the autoantibodies described in RA, anticitrullinated
      protein antibodies (ACPAs) are highly specific and predictive for RA. In
      addition, ACPAs have been implicated in the pathogenesis of RA. However, a direct
      functional response of immune cells from ACPA(+) RA patients toward citrullinated
      proteins has not been demonstrated. In this study, we show that exposure to
      citrullinated antigens leads to activation of basophils from ACPA(+) RA patients
      within 20 minutes. This was not observed after exposure of basophils to
      noncitrullinated control antigens or after stimulation of basophils from ACPA(-)
      RA patients and healthy controls. Basophil activation was correlated with the
      binding of citrullinated proteins to basophils. Furthermore, serum from ACPA(+)
      RA patients in contrast to that from ACPA(-) RA patients could specifically
      sensitize human FcepsilonRI expressing rat basophil cells (RBL), enabling
      activation by citrullinated proteins. Mast cell degranulation products such as
      histamine levels were enhanced in synovial fluid of ACPA(+) RA patients as
      compared with ACPA(-) RA and osteoarthritis patients. In addition, histamine
      levels in synovial fluid from ACPA(+) RA patients correlated with IgE levels,
      suggesting degranulation of mast cells by cross-linking IgE. Immunohistochemistry
      on synovial biopsies demonstrated an increased number of degranulated CD117(+)
      mast cells in ACPA(+) RA patients; IgE and FcepsilonRI expression in synovial
      mast cells from ACPA(+) RA patients was increased. In conclusion, our results
      show an immunological response of immune cells from ACPA(+) RA patients in a
      citrulline-specific manner. Moreover, these data indicate a role for IgE-ACPAs
      and FcepsilonRI-positive cells in the pathogenesis of RA.

PMID- 20133792
TI  - Model tests of gliding with different hindwing configurations in the four-winged
      dromaeosaurid Microraptor gui.
AB  - Fossils of the remarkable dromaeosaurid Microraptor gui and relatives clearly
      show well-developed flight feathers on the hind limbs as well as the front limbs.
      No modern vertebrate has hind limbs functioning as independent, fully developed
      wings; so, lacking a living example, little agreement exists on the functional
      morphology or likely flight configuration of the hindwing. Using a detailed
      reconstruction based on the actual skeleton of one individual, cast in the round,
      we developed light-weight, three-dimensional physical models and performed glide
      tests with anatomically reasonable hindwing configurations. Models were tested
      with hindwings abducted and extended laterally, as well as with a previously
      described biplane configuration. Although the hip joint requires the hindwing to
      have at least 20 degrees of negative dihedral (anhedral), all configurations were
      quite stable gliders. Glide angles ranged from 3 degrees to 21 degrees with a
      mean estimated equilibrium angle of 13.7 degrees, giving a lift to drag ratio of
      4.1:1 and a lift coefficient of 0.64. The abducted hindwing model's equilibrium
      glide speed corresponds to a glide speed in the living animal of 10.6 m x s(-1).
      Although the biplane model glided almost as well as the other models, it was
      structurally deficient and required an unlikely weight distribution (very heavy
      head) for stable gliding. Our model with laterally abducted hindwings represents
      a biologically and aerodynamically reasonable configuration for this four-winged
      gliding animal. M. gui's feathered hindwings, although effective for gliding,
      would have seriously hampered terrestrial locomotion.

PMID- 20133793
TI  - Two physically, functionally, and developmentally distinct peritoneal macrophage
      subsets.
AB  - The peritoneal cavity (PerC) is a unique compartment within which a variety of
      immune cells reside, and from which macrophages (MO) are commonly drawn for
      functional studies. Here we define two MO subsets that coexist in PerC in adult
      mice. One, provisionally called the large peritoneal MO (LPM), contains
      approximately 90% of the PerC MO in unstimulated animals but disappears rapidly
      from PerC following lipopolysaccharide (LPS) or thioglycolate stimulation. These
      cells express high levels of the canonical MO surface markers, CD11b and F4/80.
      The second subset, referred to as small peritoneal MO (SPM), expresses
      substantially lower levels of CD11b and F4/80 but expresses high levels of MHC
      II, which is not expressed on LPM. SPM, which predominates in PerC after LPS or
      thioglycolate stimulation, does not derive from LPM. Instead, it derives from
      blood monocytes that rapidly enter the PerC after stimulation and differentiate
      to mature SPM within 2 to 4 d. Both subsets show clear phagocytic activity and
      both produce nitric oxide (NO) in response to LPS stimulation in vivo. However,
      their responses to LPS show key differences: in vitro, LPS stimulates LPM, but
      not SPM, to produce NO; in vivo, LPS stimulates both subsets to produce NO,
      albeit with different response patterns. These findings extend current models of
      MO heterogeneity and shed new light on PerC MO diversity, development, and
      function. Thus, they introduce a new context for interpreting (and
      reinterpreting) data from ex vivo studies with PerC MO.

PMID- 20133794
TI  - Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T
      cells.
AB  - Trafficking of transmembrane receptors to a specific intracellular compartment is
      conducted by adaptor molecules that bind to target motifs within the cytoplasmic
      domains of cargo proteins. We generated mice containing a lymphoid-specific
      deficiency of AP-1 using RNAi knockdown technology. Inhibition of AP-1 expression
      in thymocytes blocks progression from double-positive immature thymocytes,
      resulting in complete absence of CD4(+) single-positive thymocytes and severe
      reduction of CD3(+)CD8(+) single-positive thymocytes. Analysis of the
      contribution of AP-1 deficiency on the interaction between mature CD4(+) T cells
      and antigen-presenting cells revealed that AP-1 is essential to efficient immune
      synapse formation and associated T cell activation, suggesting a possible
      mechanism of AP-1 function in thymocyte development.

PMID- 20133795
TI  - Genome-minimized Streptomyces host for the heterologous expression of secondary
      metabolism.
AB  - To construct a versatile model host for heterologous expression of genes encoding
      secondary metabolite biosynthesis, the genome of the industrial microorganism
      Streptomyces avermitilis was systematically deleted to remove nonessential genes.
      A region of more than 1.4 Mb was deleted stepwise from the 9.02-Mb S. avermitilis
      linear chromosome to generate a series of defined deletion mutants, corresponding
      to 83.12-81.46% of the wild-type chromosome, that did not produce any of the
      major endogenous secondary metabolites found in the parent strain. The
      suitability of the mutants as hosts for efficient production of foreign
      metabolites was shown by heterologous expression of three different exogenous
      biosynthetic gene clusters encoding the biosynthesis of streptomycin (from S.
      griseus Institute for Fermentation, Osaka [IFO] 13350), cephamycin C (from S.
      clavuligerus American type culture collection (ATCC) 27064), and pladienolide
      (from S. platensis Mer-11107). Both streptomycin and cephamycin C were
      efficiently produced by individual transformants at levels higher than those of
      the native-producing species. Although pladienolide was not produced by a
      deletion mutant transformed with the corresponding intact biosynthetic gene
      cluster, production of the macrolide was enabled by introduction of an extra copy
      of the regulatory gene pldR expressed under control of an alternative promoter.
      Another mutant optimized for terpenoid production efficiently produced the plant
      terpenoid intermediate, amorpha-4,11-diene, by introduction of a synthetic gene
      optimized for Streptomyces codon usage. These findings highlight the strength and
      flexibility of engineered S. avermitilis as a model host for heterologous gene
      expression, resulting in the production of exogenous natural and unnatural
      metabolites.

PMID- 20133796
TI  - Bimodular auxin response controls organogenesis in Arabidopsis.
AB  - Like animals, the mature plant body develops via successive sets of instructions
      that determine cell fate, patterning, and organogenesis. In the coordination of
      various developmental programs, several plant hormones play decisive roles, among
      which auxin is the best-documented hormonal signal. Despite the broad range of
      processes influenced by auxin, how such a single signaling molecule can be
      translated into a multitude of distinct responses remains unclear. In Arabidopsis
      thaliana, lateral root development is a classic example of a developmental
      process that is controlled by auxin at multiple stages. Therefore, we used
      lateral root formation as a model system to gain insight into the
      multifunctionality of auxin. We were able to demonstrate the complementary and
      sequential action of two discrete auxin response modules, the previously
      described Solitary Root/indole-3-Acetic Acid (IAA)14-Auxin Response Factor (ARF)7
      ARF19-dependent lateral root initiation module and the successive Bodenlos/IAA12
      Monopteros/ARF5-dependent module, both of which are required for proper
      organogenesis. The genetic framework in which two successive auxin response
      modules control early steps of a developmental process adds an extra dimension to
      the complexity of auxin's action.

PMID- 20133797
TI  - Differential release of chromatin-bound IL-1alpha discriminates between necrotic
      and apoptotic cell death by the ability to induce sterile inflammation.
AB  - IL-1alpha, like IL-1beta, possesses multiple inflammatory and immune properties.
      However, unlike IL-1beta, the cytokine is present intracellularly in healthy
      tissues and is not actively secreted. Rather, IL-1alpha translocates to the
      nucleus and participates in transcription. Here we show that intracellular IL
      1alpha is a chromatin-associated cytokine and highly dynamic in the nucleus of
      living cells. During apoptosis, IL-1alpha concentrates in dense nuclear foci,
      which markedly reduces its mobile nature. In apoptotic cells, IL-1alpha is
      retained within the chromatin fraction and is not released along with the
      cytoplasmic contents. To simulate the in vivo inflammatory response to cells
      undergoing different mechanisms of death, lysates of cells were embedded in
      Matrigel plugs and implanted into mice. Lysates from cells undergoing necrosis
      recruited cells of the myeloid lineage into the Matrigel, whereas lysates of
      necrotic cells lacking IL-1alpha failed to recruit an infiltrate. In contrast,
      lysates of cells undergoing apoptotic death were inactive. Cells infiltrating the
      Matrigel were due to low concentrations (20-50 pg) of the IL-1alpha precursor
      containing the receptor interacting C-terminal, whereas the N-terminal propiece
      containing the nuclear localization site failed to do so. When normal
      keratinocytes were subjected to hypoxia, the constitutive IL-1alpha precursor was
      released into the supernatant. Thus, after an ischemic event, the IL-1alpha
      precursor is released by hypoxic cells and incites an inflammatory response by
      recruiting myeloid cells into the area. Tissues surrounding the necrotic site
      also sustain damage from the myeloid cells. Nuclear trafficking and differential
      release during necrosis vs. apoptosis demonstrate that inflammation by IL-1alpha
      is tightly controlled.

PMID- 20133798
TI  - Plastic modifications induced by object recognition memory processing.
AB  - Long-term potentiation (LTP) phenomenon is widely accepted as a cellular model of
      memory consolidation. Object recognition (OR) is a particularly useful way of
      studying declarative memory in rodents because it makes use of their innate
      preference for novel over familiar objects. In this study, mice had electrodes
      implanted in the hippocampal Schaffer collaterals-pyramidal CA1 pathway and were
      trained for OR. Field EPSPs evoked at the CA3-CA1 synapse were recorded at the
      moment of training and at different times thereafter. LTP-like synaptic
      enhancement was found 6 h posttraining. A testing session was conducted 24 h
      after training, in the presence of one familiar and one novel object. Hippocampal
      synaptic facilitation was observed during exploration of familiar and novel
      objects. A short depotentiation period was observed early after the test and was
      followed by a later phase of synaptic efficacy enhancement. Here, we show that OR
      memory consolidation is accompanied by transient potentiation in the hippocampal
      CA3-CA1 synapses, while reconsolidation of this memory requires a short-lasting
      phase of depotentiation that could account for its well described vulnerability.
      The late synaptic enhancement phase, on the other hand, would be a consequence of
      memory restabilization.

PMID- 20133799
TI  - Flow enhances photosynthesis in marine benthic autotrophs by increasing the
      efflux of oxygen from the organism to the water.
AB  - Worldwide, many marine coastal habitats are facing rapid deterioration due in
      part to human-driven changes in habitat characteristics, including changes in
      flow patterns, a factor known to greatly affect primary production in corals,
      algae, and seagrasses. The effect of flow traditionally is attributed to enhanced
      influx of nutrients and dissolved inorganic carbon (DIC) across the benthic
      boundary layer from the water to the organism however, here we report that the
      organism's photosynthetic response to changes in the flow is nearly
      instantaneous, and that neither nutrients nor DIC limits this rapid response.
      Using microelectrodes, dual-pulse amplitude-modulated fluorometry, particle image
      velocimetry, and real time mass-spectrometry with the common scleractinian coral
      Favia veroni, the alga Gracilaria cornea, and the seagrass Halophila stipulacea,
      we show that this augmented photosynthesis is due to flow-driven enhancement of
      oxygen efflux from the organism to the water, which increases the affinity of the
      RuBisCO to CO(2). No augmentation of photosynthesis was found in the absence of
      flow or when flow occurred, but the ambient concentration of oxygen was
      artificially elevated. We suggest that water motion should be considered a
      fundamental factor, equivalent to light and nutrients, in determining
      photosynthesis rates in marine benthic autotrophs.

PMID- 20133800
TI  - Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant
      cancer cells.
AB  - Paclitaxel has emerged as a front line treatment for aggressive malignancies of
      the breast, lung, and ovary. Successful therapy of cancer is frequently
      undermined by the development of paclitaxel resistance. There is a growing need
      to find other therapeutic targets to facilitate treatment of drug-resistant
      cancers. Using a proteomics approach, elevated levels of Prohibitin1 (PHB1) and
      GSTpi were found associated with paclitaxel resistance in discrete subcellular
      fractions of two drug-resistant sublines relative to their sensitive sublines.
      Immunofluorescence staining and fractionation studies revealed increased levels
      of PHB1 on the surface of resistant cell lines. Transiently silencing either PHB1
      or GSTpi gene expression using siRNA in the paclitaxel-resistant cancer cell
      sublines partially sensitized these cells toward paclitaxel. Intriguingly,
      silencing PHB1 but not GSTpi resulted in activation of the intrinsic apoptosis
      pathway in response to paclitaxel. Similarly, stably silencing either PHB1 or
      GSTpi significantly improved paclitaxel sensitivity in A549TR cells both in vitro
      and in vivo. Our results indicate that PHB1 is a mediator of paclitaxel
      resistance and that this resistance may depend on the cellular localization of
      the protein. We suggest PHB1 as a potential target for therapeutic strategies for
      the treatment of drug-resistant tumors.

PMID- 20133801
TI  - Prelimbic cortical BDNF is required for memory of learned fear but not extinction
      or innate fear.
AB  - In the medial prefrontal cortex, the prelimbic area is emerging as a major
      modulator of fear behavior, but the mechanisms remain unclear. Using a selective
      neocortical knockout mouse, virally mediated prelimbic cortical-specific gene
      deletion, and pharmacological rescue with a TrkB agonist, we examined the role of
      a primary candidate mechanism, BDNF, in conditioned fear. We found consistently
      robust deficits in consolidation of cued fear but no effects on acquisition,
      expression of unlearned fear, sensorimotor function, and spatial learning. This
      deficit in learned fear in the BDNF knockout mice was rescued with systemic
      administration of a TrkB receptor agonist, 7,8-dihydroxyflavone. These data
      indicate that prelimbic BDNF is critical for consolidation of learned fear
      memories, but it is not required for innate fear or extinction of fear. Moreover,
      use of site-specific, inducible BDNF deletions shows a powerful mechanism that
      may further our understanding of the pathophysiology of fear-related disorders.

PMID- 20133802
TI  - Breakdown in cortical effective connectivity during midazolam-induced loss of
      consciousness.
AB  - By employing transcranial magnetic stimulation (TMS) in combination with high
      density electroencephalography (EEG), we recently reported that cortical
      effective connectivity is disrupted during early non-rapid eye movement (NREM)
      sleep. This is a time when subjects, if awakened, may report little or no
      conscious content. We hypothesized that a similar breakdown of cortical effective
      connectivity may underlie loss of consciousness (LOC) induced by pharmacologic
      agents. Here, we tested this hypothesis by comparing EEG responses to TMS during
      wakefulness and LOC induced by the benzodiazepine midazolam. Unlike spontaneous
      sleep states, a subject's level of vigilance can be monitored repeatedly during
      pharmacological LOC. We found that, unlike during wakefulness, wherein TMS
      triggered responses in multiple cortical areas lasting for >300 ms, during
      midazolam-induced LOC, TMS-evoked activity was local and of shorter duration.
      Furthermore, a measure of the propagation of evoked cortical currents
      (significant current scattering, SCS) could reliably discriminate between
      consciousness and LOC. These results resemble those observed in early NREM sleep
      and suggest that a breakdown of cortical effective connectivity may be a common
      feature of conditions characterized by LOC. Moreover, these results suggest that
      it might be possible to use TMS-EEG to assess consciousness during anesthesia and
      in pathological conditions, such as coma, vegetative state, and minimally
      conscious state.

PMID- 20133803
TI  - Alternative end-joining catalyzes robust IgH locus deletions and translocations
      in the combined absence of ligase 4 and Ku70.
AB  - Class switch recombination (CSR) in B lymphocytes is initiated by introduction of
      multiple DNA double-strand breaks (DSBs) into switch (S) regions that flank
      immunoglobulin heavy chain (IgH) constant region exons. CSR is completed by
      joining a DSB in the donor S mu to a DSB in a downstream acceptor S region (e.g.,
      S gamma1) by end-joining. In normal cells, many CSR junctions are mediated by
      classical nonhomologous end-joining (C-NHEJ), which employs the Ku70/80 complex
      for DSB recognition and XRCC4/DNA ligase 4 for ligation. Alternative end-joining
      (A-EJ) mediates CSR, at reduced levels, in the absence of C-NHEJ, even in
      combined absence of Ku70 and ligase 4, demonstrating an A-EJ pathway totally
      distinct from C-NHEJ. Multiple DSBs are introduced into S mu during CSR, with
      some being rejoined or joined to each other to generate internal switch deletions
      (ISDs). In addition, S-region DSBs can be joined to other chromosomes to generate
      translocations, the level of which is increased by absence of a single C-NHEJ
      component (e.g., XRCC4). We asked whether ISD and S-region translocations occur
      in the complete absence of C-NHEJ (e.g., in Ku70/ligase 4 double-deficient B
      cells). We found, unexpectedly, that B-cell activation for CSR generates
      substantial ISD in both S mu and S gamma1 and that ISD in both is greatly
      increased by the absence of C-NHEJ. IgH chromosomal translocations to the c-myc
      oncogene also are augmented in the combined absence of Ku70 and ligase 4. We
      discuss the implications of these findings for A-EJ in normal and abnormal DSB
      repair.

PMID- 20133804
TI  - A role for FKBP52 in Tau protein function.
AB  - Tau is a microtubule-associated protein, which is widely expressed in the central
      nervous system, predominantly in neurons, where it regulates microtubule
      dynamics, axonal transport, and neurite outgrowth. The aberrant assembly of Tau
      is the hallmark of several human neurodegenerative diseases, collectively known
      as tauopathies. They include Alzheimer's disease, Pick's disease, progressive
      supranuclear palsy, and frontotemporal dementia and parkinsonism linked to
      chromosome 17. Several abnormalities in Tau, such as hyperphosphorylation and
      aggregation, alter its function and are central to the pathogenic process. Here,
      we describe biochemical and functional interactions between FKBP52 and Tau.
      FKBP52 is a member of the FKBP (FK506-binding protein) family that comprises
      intracellular protein effectors of immunosuppressive drugs (such as FK506 and
      rapamycin). We found that FKBP52, which is abundant in brain, binds directly and
      specifically to Tau, especially in its hyperphosphorylated form. The relevance of
      this observation was confirmed by the colocalization of both proteins in the
      distal part of the axons of cortical neurons and by the antagonistic effect of
      FKBP52 on the ability of Tau to promote microtubule assembly. Overexpression of
      FKBP52 in differentiated PC12 cells prevented the accumulation of Tau and
      resulted in reduced neurite length. Taken together, these findings indicate a
      role for FKBP52 in Tau function and may help to decipher and modulate the events
      involved in Tau-induced neurodegeneration.

PMID- 20133805
TI  - Symplekin promotes tumorigenicity by up-regulating claudin-2 expression.
AB  - Symplekin is a ubiquitously expressed protein involved in cytoplasmic RNA
      polyadenylation and transcriptional regulation and is localized at tight
      junctions (TJs) in epithelial cells. Nuclear symplekin cooperates with the Y-box
      transcription factor zonula occludens 1-associated nucleic acid-binding protein
      (ZONAB) to increase the transcription of cell cycle-related genes and also
      inhibits differentiation of intestinal cells. We detected high levels of nuclear
      symplekin in 8 of 12 human colorectal cancer (CRC) samples. shRNA-mediated
      reduction of symplekin expression was sufficient to decrease significantly the
      anchorage-independent growth and proliferation of HT-29 CRC cells as well as
      their tumorigenicity when injected into immunodeficient animals. Symplekin down
      regulation also was found to alter ion transport through TJs, to promote the
      localization of ZONAB in the membrane rather than the nucleus, and strongly to
      enhance cell polarization in a 3D matrix, leading to the formation of spheroids
      organized around a central lumen. Claudin-2 expression was reduced following
      symplekin down-regulation, an effect mimicked when ZONAB expression was down
      regulated using selective siRNA. Virus-mediated restoration of claudin-2
      expression was found to restore nuclear expression of ZONAB in HT29DeltaSym cells
      and to rescue the phenotypic alterations induced by symplekin down-regulation of
      cell polarity, paracellular transport, ZONAB localization, cyclin D1 expression,
      proliferation, and anchorage-independent growth. Finally, siRNA-mediated claudin
      2 down-regulation increased the transepithelial resistance and decreased cyclin
      D1 expression and ZONAB nuclear localization, similar to observations in
      symplekin-depleted cells. Our results suggest that nuclear overexpression of
      symplekin promotes tumorigenesis in the human colon and that the regulation of
      claudin-2 expression is instrumental in this effect.

PMID- 20133806
TI  - Basal epithelial stem cells are efficient targets for prostate cancer initiation.
AB  - Prevailing theories suggest that luminal cells are the origin of prostate cancer
      because it is histologically defined by basal cell loss and malignant luminal
      cell expansion. We introduced a series of genetic alterations into prospectively
      identified populations of murine basal/stem and luminal cells in an in vivo
      prostate regeneration assay. Stromal induction of FGF signaling, increased
      expression of the ETS family transcription factor ERG1, and constitutive
      activation of PI3K signaling were evaluated. Combination of activated PI3K
      signaling and heightened androgen receptor signaling, which is associated with
      disease progression to androgen independence, was also performed. Even though
      luminal cells fail to respond, basal/stem cells demonstrate efficient capacity
      for cancer initiation and can produce luminal-like disease characteristic of
      human prostate cancer in multiple models. This finding provides evidence in
      support of basal epithelial stem cells as one target cell for prostate cancer
      initiation and demonstrates the propensity of primitive cells for tumorigenesis.

PMID- 20133807
TI  - A truncated lipoglycan from mycobacteria with altered immunological properties.
AB  - Maintenance of cell-wall integrity in Mycobacterium tuberculosis is essential and
      is the target of several antitubercular drugs. For example, ethambutol targets
      arabinogalactan and lipoarabinomannan (LAM) biosynthesis through the inhibition
      of several arabinofuranosyltransferases. Apart from their role in cell-wall
      integrity, mycobacterial LAMs also exhibit important immunomodulatory activities.
      Here we report the isolation and detailed structural characterization of a unique
      LAM molecule derived from Mycobacterium smegmatis deficient in the
      arabinofuranosyltransferase AftC (AftC-LAM). This mutant LAM expresses a severely
      truncated arabinan domain completely devoid of 3,5-Araf-branching residues,
      revealing an intrinsic involvement of AftC in the biosynthesis of LAM.
      Furthermore, we found that ethambutol efficiently inhibits biosynthesis of the
      AftC-LAM arabinan core, unambiguously demonstrating the involvement of the
      arabinofuranosyltransferase EmbC in early stages of LAM-arabinan biosynthesis.
      Finally, we demonstrate that AftC-LAM exhibits an enhanced proinflammatory
      activity, which is due to its ability to activate Toll-like receptor 2 (TLR2).
      Overall, our efforts further describe the mechanism of action of an important
      antitubercular drug, ethambutol, and demonstrate a role for specific
      arabinofuranosyltransferases in LAM biosynthesis. In addition, the availability
      of sufficient amounts of chemically defined wild-type and isogenic truncated LAMs
      paves the way for further investigations of the structure-function relationship
      of TLR2 activation by mycobacterial lipoglycans.

PMID- 20133808
TI  - Coordination of plant cell division and expansion in a simple morphogenetic
      system.
AB  - Morphogenesis in plants arises from the interplay of genetic and physical
      interactions within a growing network of cells. The physical aspects of cell
      proliferation and differentiation are genetically regulated, but constrained by
      mechanical interactions between the cells. Higher plant tissues consist of an
      elaborate three-dimensional matrix of active cytoplasm and extracellular matrix,
      where it is difficult to obtain direct measurements of geometry or cell
      interactions. To properly understand the workings of plant morphogenesis, it is
      necessary to have biological systems that allow simple and direct observation of
      these processes. We have adopted a highly simplified plant system to investigate
      how cell proliferation and expansion is coordinated during morphogenesis.
      Coleocheate scutata is a microscopic fresh-water green alga with simple
      anatomical features that allow for accurate quantification of morphogenetic
      processes. Image analysis techniques were used to extract precise models for cell
      geometry and physical parameters for growth. This allowed construction of a
      deformable finite element model for growth of the whole organism, which
      incorporated cell biophysical properties, viscous expansion of cell walls, and
      rules for regulation of cell behavior. The study showed that a simple set of
      autonomous, cell-based rules are sufficient to account for the morphological and
      dynamic properties of Coleochaete growth. A variety of morphogenetic behavior
      emerged from the application of these local rules. Cell shape sensing is
      sufficient to explain the patterns of cell division during growth. This
      simplifying principle is likely to have application in modeling and design for
      engineering of higher plant tissues.

PMID- 20133809
TI  - Influence of lever structure on myosin 5a walking.
AB  - Using electron microscopy and image processing, we have observed myosin 5a
      modified with lever arms of different lengths (four, six, and eight calmodulin
      binding IQ domains) and orientations walking along actin filaments. Step lengths
      were dependent on lever length: 8IQ > 6IQ > 4IQ, which is consistent with myosin
      5a having evolved to walk straight along actin. Lead heads were mostly in the
      prepowerstroke state, tethered there by the trail head. However, improved image
      processing showed that in 5-10% of molecules the lead motor was in the
      postpowerstroke state. This is a unique attached state of myosin, where the motor
      domain has completed its powerstroke at the expense of severe lever distortion,
      but with little cargo movement. Postpowerstroke lead heads were seen in both wild
      type and modified lever molecules, mostly where there was least strain. These
      data allow the strain dependence of the equilibrium between pre- and
      postpowerstroke conformations to be measured. Slow rates of ADP dissociation
      observed from lead heads of these molecules can be explained by the unfavorable
      equilibrium between the pre- and postpowerstroke conformations preceding ADP
      loss.

PMID- 20133810
TI  - A selective TrkB agonist with potent neurotrophic activities by 7,8
      dihydroxyflavone.
AB  - Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine
      kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation,
      synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic
      profile that limits its therapeutic potential. Here we report the identification
      of 7,8-dihydroxyflavone as a bioactive high-affinity TrkB agonist that provokes
      receptor dimerization and autophosphorylation and activation of downstream
      signaling. 7,8-Dihydroxyflavone protected wild-type, but not TrkB-deficient,
      neurons from apoptosis. Administration of 7,8-dihydroxyflavone to mice activated
      TrkB in the brain, inhibited kainic acid-induced toxicity, decreased infarct
      volumes in stroke in a TrkB-dependent manner, and was neuroprotective in an
      animal model of Parkinson disease. Thus, 7,8-dihydroxyflavone imitates BDNF and
      acts as a robust TrkB agonist, providing a powerful therapeutic tool for the
      treatment of various neurological diseases.

PMID- 20133811
TI  - Generation of a novel transgenic mouse model for bioluminescent monitoring of
      survivin gene activity in vivo at various pathophysiological processes: survivin
      expression overlaps with stem cell markers.
AB  - Survival has been implicated to play an important role in various
      pathophysiological processes. However, because of a lack of appropriate animal
      models, the role and dynamic expression of survivin during pathophysiology are
      not well defined. We generated a human survivin gene promoter-driven luciferase
      transgenic mouse model (SPlucTg) so that dynamic survivin gene activity can be
      monitored during various pathophysiological conditions using in vivo imaging. Our
      results show that, consistent with survivin positivity in testis, luciferase
      activity in normal SPlucTg mice was detected in the testis of male mice.
      Furthermore, similar to the known requirement of transient expression of survivin
      for pathophysiological responses, we observed a transient luciferase expression
      in castrated SPlucTg male mice after supplement of androgen. Significantly, it
      was reported that survivin expression turns on during mouse liver injury and
      regeneration; a transient and dose-dependent luciferase expression in the mouse
      liver was observed after administration of carbon tetrachloride into SPlucTg
      mice. We further demonstrated that luciferase activity closely correlates with
      endogenous survivin expression. We also demonstrated that only a subset of cells
      expresses survivin, and its expression overlaps with the expression of several
      stem cell markers tested. Thus, we have generated a unique animal model for
      analysis of diverse pathophysiological processes and possible stem cell
      distribution/activity in vivo.

PMID- 20133812
TI  - Epithelial-stromal interaction 1 (EPSTI1) substitutes for peritumoral fibroblasts
      in the tumor microenvironment.
AB  - Tumor cells can activate stroma, yet the implication of this activation in terms
      of reciprocal induction of gene expression in tumor cells is poorly understood.
      Epithelial Stromal Interaction 1 (EPSTI1) is an interferon response gene
      originally isolated from heterotypic recombinant cultures of human breast cancer
      cells and activated breast myofibroblasts. Here we describe the first
      immunolocalization of EPSTI1 in normal and cancerous breast tissue, and we
      provide evidence for a role of this molecule in the regulation of tumor cell
      properties and epithelial-mesenchymal transition. In general, no EPSTI1 staining
      was observed in normal breast epithelial cells from reduction mammoplasties
      (n=25). However, in carcinomas, staining was positive in 22 of 40 biopsies and
      inversely correlated with the level of differentiation. To address the function
      of EPSTI1, we expressed EPSTI1 ectopically in one cell line and silenced
      endogenous EPSTI1 by RNA interference in another. Irrespective of the
      experimental approach, EPSTI1 expression led to an increase in tumorsphere
      formation-a property associated with breast stem/progenitor cells. Most
      remarkably, we show that EPSTI1, by conveying spread of tumor cells, can replace
      peritumoral activated fibroblasts in a tumor environment assay. These
      observations implicate EPSTI1 as a hitherto unappreciated regulator of tumor cell
      properties.

PMID- 20133813
TI  - The CD40-CD40L pathway contributes to the proinflammatory function of intestinal
      epithelial cells in inflammatory bowel disease.
AB  - In inflammatory bowel diseases (IBD), intestinal epithelial cells (IECs) are
      involved in the outbalanced immune responses toward luminal antigens. However,
      the signals responsible for this proinflammatory capacity of IECs in IBD remain
      unclear. The CD40/CD40L interaction activates various pathways in immune and
      nonimmune cells related to inflammation and was shown to be critical for the
      development of IBD. Here we demonstrate CD40 expression within IECs during active
      IBD. Endoscopically obtained biopsies taken from Crohn's disease (n = 112) and
      ulcerative colitis patients (n = 67) consistently showed immunofluorescence
      staining for CD40 in IECs of inflamed ileal or colonic mucosa. In noninvolved
      mucosa during active disease, tissue obtained during Crohn's disease or
      ulcerative colitis in remission and biopsies from healthy controls (n = 38) IECs
      almost entirely lacked CD40 staining. Flow cytometry and RT-PCR analysis using
      different intestinal epithelial cell lines (HT29, SW480, and T84) showed IFN
      gamma to effectively induce CD40 in IECs. Cells were virtually unresponsive to
      LPS or whole E. coli regarding CD40 expression. In addition, a moderate induction
      of CD40 was found in response to TNF-alpha, which exerted synergistical effects
      with IFN-gamma. CD40 ligation by CD40L-transfected murine fibroblasts or soluble
      CD40L increased the secretion of IL-8 in IFN-gamma pretreated HT29 cells. Our
      findings provide evidence for the epithelial expression and modulation of CD40 in
      IBD-affected mucosa and indicate its involvement in the proinflammatory function
      of IECs.

PMID- 20133814
TI  - Novel EphB4 monoclonal antibodies modulate angiogenesis and inhibit tumor growth.
AB  - EphB4 receptor tyrosine kinase and its cognate ligand EphrinB2 regulate induction
      and maturation of newly forming vessels. Inhibition of their interaction arrests
      angiogenesis, vessel maturation, and pericyte recruitment. In addition, EphB4 is
      expressed in the vast majority of epithelial cancers and provides a survival
      advantage to most. Here, we describe two anti-EphB4 monoclonal antibodies that
      inhibit tumor angiogenesis and tumor growth by two distinct pathways. MAb131
      binds to fibronectin-like domain 1 and induces degradation of human EphB4, but
      not murine EphB4. MAb131 inhibits human endothelial tube formation in vitro and
      growth of human tumors expressing EphB4 in vivo. In contrast, MAb47 targets
      fibronectin-like domain 2 of both human and murine EphB4 and does not alter EphB4
      receptor levels, but inhibits angiogenesis and growth of both EphB4-positive and
      EphB4-negative tumors in a mouse s.c. xenograft model. Combination of MAb47 and
      bevacizumab enhances the antitumor activity and induces tumor regression. Indeed,
      humanized antibodies hAb47 and hAb131 showed similar affinity for EphB4 and
      retained efficacy in the inhibition of primary tumor development and experimental
      metastasis.

PMID- 20133815
TI  - Hypoxic regulation of nucleus pulposus cell survival: from niche to notch.
AB  - This minireview examines the role of hypoxia, and hypoxia inducible factors (HIF
      1 and HIF-2), in regulating the metabolism, function, and fate of cells of the
      nucleus pulposus in the intervertebral disk. We focus on the mechanisms by which
      both these hypoxia-sensitive transcription factors influence energy metabolism,
      radical dismutation, and expression of survival proteins. In addition, we discuss
      how cells of the nucleus respond to a number of hypoxia-sensitive proteins,
      including galectin-3, Akt, and VEGF. Where applicable, these discussions are
      extended to include the impact of these molecules and hypoxia on degenerating
      resident cells in the intervertebral niche. Finally, because the notch signaling
      pathway is responsive to hypoxia, we speculate that in the intervertebral niche,
      notch proteins participate in the regulation of disk precursor cell proliferation
      and differentiation. We predict that knowledge of each of these interactive
      proteins within the disk niche could be used to enhance renewal and promote
      differentiation and function of cells of the nucleus pulposus.

PMID- 20133816
TI  - Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage: evidence from
      patients with delta-storage pool deficiencies.
AB  - We previously showed that the MRP4 (ABCC4) transporter is expressed in human
      platelet delta-granules and may be involved in ADP transport. We now demonstrate
      by immunoblotting and immunofluorescence microscopy that platelet MRP4 is absent
      in two patients with a platelet delta-storage pool deficiency (delta-SPD)-like
      phenotype with reduced platelet adenine nucleotide (AN) but normal serotonin
      levels, whereas their other membrane marker proteins of platelet granules were
      normally expressed and localized. In these patients, MRP4 was present in
      lymphocytes, and the coding region of their MRP4/ABCC4 gene did not show any
      mutation that explained the lack of expression. In platelets with "classic" delta
      SPD (low AN and serotonin levels), MRP4 was quantitatively (immunoblot) normal,
      but, like other delta-granules membrane marker proteins (eg, LAMP2), was mostly
      displaced from delta-granules to patches at the plasma membrane, suggesting that
      platelets with classic delta-SPD have an abnormality that impairs the assembly of
      normal delta-granules. Thus, defective expression of platelet MRP4 is associated
      with selective defect in AN storage. The genetic basis of the new delta-SPD
      phenotype remains to be elucidated.

PMID- 20133817
TI  - Effects of CXCR4 gene transfer on cardiac function after ischemia-reperfusion
      injury.
AB  - Acute coronary occlusion is the leading cause of death in the Western world.
      There is an unmet need for the development of treatments to limit the extent of
      myocardial infarction (MI) during the acute phase of occlusion. Recently,
      investigators have focused on the use of a chemokine, CXCL12, the only identified
      ligand for CXCR4, as a new therapeutic modality to recruit stem cells to
      individuals suffering from MI. Here, we examined the effects of overexpression of
      CXCR4 by gene transfer on MI. Adenoviruses carrying the CXCR4 gene were injected
      into the rat heart one week before ligation of the left anterior descending
      coronary artery followed by 24 hours reperfusion. Cardiac function was assessed
      by echocardiography couple with 2,3,5-Triphenyltetrazolium chloride staining to
      measure MI size. In comparison with control groups, rats receiving Ad-CXCR4
      displayed an increase in infarct area (13.5% +/- 4.1%) and decreased fractional
      shortening (38% +/- 5%). Histological analysis revealed a significant increase in
      CXCL12 and tumor necrosis factor-alpha expression in ischemic area of CXCR4
      overexpressed hearts. CXCR4 overexpression was associated with increased influx
      of inflammatory cells and enhanced cardiomyocyte apoptosis in the infarcted
      heart. These data suggest that in our model overexpressing CXCR4 appears to
      enhance ischemia/reperfusion injury possibly due to enhanced recruitment of
      inflammatory cells, increased tumor necrosis factor-alpha production, and
      activation of cell death/apoptotic pathways.

PMID- 20133818
TI  - Angiopoietin/Tie2 signaling transforms capillaries into venules primed for
      leukocyte trafficking in airway inflammation.
AB  - Vascular endothelial growth factor (VEGF) is a key angiogenic factor in tumors,
      but less is known about what drives vascular remodeling in inflammation, where
      plasma leakage and leukocyte influx are prominent features. In chronic airway
      inflammation in mice infected by the bacterium Mycoplasma pulmonis (M. pulmonis),
      the segment of the microvasculature that supports leukocyte adhesion and
      migration expands through remodeling of capillaries into vessels with features of
      venules. Here, we report that the angiopoietin/Tie2 pathway is an essential
      driving force for capillary remodeling into venules in M. pulmonis-infected mouse
      airways. Similar to M. pulmonis infection, systemic overexpression of
      angiopoietin-1 (Ang1) resulted in remodeling of airway capillaries into venular
      like vessels that expressed venous markers like P-selectin, ICAM-1, and EphB4 and
      were sites of leukocyte adhesion during lipopolysaccharide-induced acute
      inflammation. Ang1 and Ang2 protein increased in M. pulmonis-infected mouse
      airways but came from different cellular sources: Ang1 was expressed in
      infiltrating neutrophils and Ang2 in endothelial cells. Indeed, systemic
      administration of soluble Tie2 inhibited capillary remodeling, induction of
      venous markers, and leukocyte influx in M. pulmonis-infected mouse airways.
      Together, these findings suggest that blockade of the Ang/Tie2 pathway may
      represent a therapeutic approach in airway inflammation.

PMID- 20133819
TI  - Endogenous angiogenesis inhibitor vasohibin1 exhibits broad-spectrum
      antilymphangiogenic activity and suppresses lymph node metastasis.
AB  - During cancer progression, the angiogenesis that occurs is involved in tumor
      growth and hematogenous-distant metastasis, whereas lymphangiogenesis is involved
      in regional lymph node metastasis. Angiogenesis is counterregulated by various
      endogenous inhibitors; however, little is known about endogenous inhibitors of
      lymphangiogenesis. We recently isolated vasohibin1 as an angiogenesis inhibitor
      intrinsic to the endothelium and further demonstrated its anticancer activity
      through angiogenesis inhibition. Here, we examined the effect of vasohibin1 on
      lymphangiogenesis. Vasohibin1 exhibited broad-spectrum antilymphangiogenic
      activity in the mouse cornea induced by factors including VEGF-A, VEGF-C, FGF2,
      and PDGF-BB. We then inoculated highly lymph node-metastatic cancer cells into
      mice and examined the effect of vasohibin1 on lymph node metastasis. Tail-vein
      injection of adenovirus containing the human vasohibin1 gene inhibited tumor
      lymphangiogenesis and regional lymph node metastasis. Moreover, local injection
      of recombinant vasohibin1 inhibited lymph node metastasis. These results suggest
      vasohibin1 to be the first known intrinsic factor having broad-spectrum
      antilymphangiogenic activity and indicate that it suppresses lymph node
      metastasis.

PMID- 20133820
TI  - Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of
      patients with tuberous sclerosis complex and new therapeutic implications.
AB  - Subependymal giant cell astrocytomas (SEGAs) are rare brain tumors associated
      with tuberous sclerosis complex (TSC), a disease caused by mutations in TSC1 or
      TSC2, resulting in enhancement of mammalian target of rapamycin (mTOR) activity,
      dysregulation of cell growth, and tumorigenesis. Signaling via mTOR plays a role
      in multifaceted genomic responses, but its effectors in the brain are largely
      unknown. Therefore, gene expression profiling on four SEGAs was performed with
      Affymetrix Human Genome arrays. Of the genes differentially expressed in TSC, 11
      were validated by real-time PCR on independent tumor samples and 3 SEGA-derived
      cultures. Expression of several proteins was confirmed by immunohistochemistry.
      The differentially-regulated proteins were mainly involved in tumorigenesis and
      nervous system development. ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4, and NPTX1
      genes were likely to be mTOR effector genes in SEGA, as their expression was
      modulated by an mTOR inhibitor, rapamycin, in SEGA-derived cells. Inhibition of
      mTOR signaling affected size of cultured SEGA cells but had no influence on their
      proliferation, morphology, or migration, whereas inhibition of both mTOR and
      extracellular signal-regulated kinase signaling pathways led to significant
      alterations of these processes. For the first time, we identified genes related
      to the occurrence of SEGA and regulated by mTOR and demonstrated an effective
      modulation of SEGA growth by pharmacological inhibition of both mTOR and
      extracellular signal-regulated kinase signaling pathways, which could represent a
      novel therapeutic approach.

PMID- 20133821
TI  - Evolution in health and medicine Sackler colloquium: Evolutionary perspectives on
      health and medicine.

PMID- 20133822
TI  - Evolution in health and medicine Sackler colloquium: Genetic architecture of a
      complex trait and its implications for fitness and genome-wide association
      studies.
AB  - A model is investigated in which mutations that affect a complex trait (e.g.,
      heart disease) also affect fitness because the trait is a component of fitness or
      because the mutations have pleiotropic effects on fitness. The model predicts
      that the genetic variance, and hence the heritability, in the trait is
      contributed by mutations at low frequency in the population, unless the mean
      strength of selection of mutations that affect the trait is very small or weakly
      selected mutations tend to contribute disproportionately to the trait compared
      with strongly selected mutations. Furthermore, it is shown that each rare
      mutation tends to contribute more to the variance than each common mutation.
      These results may explain why most genome-wide association studies have failed to
      find associations that explain much of the variance. It is also shown that most
      of the variance in fitness contributed by new nonsynonymous mutations is caused
      by mutations at very low frequency in the population. This implies that most low
      frequency SNPs, which are observed in current resequencing studies of, for
      example, 100 chromosomes, probably have little impact on the variance in fitness
      or traits. Finally, it is shown that the variance contributed by a category of
      mutations (e.g., coding or regulatory) depends largely upon the mean strength of
      selection; this has implications for understanding which types of mutations are
      likely to be responsible for the variance in fitness and inherited disease.

PMID- 20133823
TI  - Protection mechanisms of the iron-plated armor of a deep-sea hydrothermal vent
      gastropod.
AB  - Biological exoskeletons, in particular those with unusually robust and
      multifunctional properties, hold enormous potential for the development of
      improved load-bearing and protective engineering materials. Here, we report new
      materials and mechanical design principles of the iron-plated multilayered
      structure of the natural armor of Crysomallon squamiferum, a recently discovered
      gastropod mollusc from the Kairei Indian hydrothermal vent field, which is unlike
      any other known natural or synthetic engineered armor. We have determined through
      nanoscale experiments and computational simulations of a predatory attack that
      the specific combination of different materials, microstructures, interfacial
      geometries, gradation, and layering are advantageous for penetration resistance,
      energy dissipation, mitigation of fracture and crack arrest, reduction of back
      deflections, and resistance to bending and tensile loads. The structure-property
      performance relationships described are expected to be of technological interest
      for a variety of civilian and defense applications.

PMID- 20133824
TI  - Genetic control over the resting brain.
AB  - The default-mode network, a coherent resting-state brain network, is thought to
      characterize basal neural activity. Aberrant default-mode connectivity has been
      reported in a host of neurological and psychiatric illnesses and in persons at
      genetic risk for such illnesses. Whereas the neurophysiologic mechanisms that
      regulate default-mode connectivity are unclear, there is growing evidence that
      genetic factors play a role. In this report, we estimate the importance of
      genetic effects on the default-mode network by examining covariation patterns in
      functional connectivity among 333 individuals from 29 randomly selected extended
      pedigrees. Heritability for default-mode functional connectivity was 0.424 +/-
      0.17 (P = 0.0046). Although neuroanatomic variation in this network was also
      heritable, the genetic factors that influence default-mode functional
      connectivity and gray-matter density seem to be distinct, suggesting that unique
      genes influence the structure and function of the network. In contrast,
      significant genetic correlations between regions within the network provide
      evidence that the same genetic factors contribute to variation in functional
      connectivity throughout the default mode. Specifically, the left parahippocampal
      region was genetically correlated with all other network regions. In addition,
      the posterior cingulate/precuneus region, medial prefrontal cortex, and right
      cerebellum seem to form a subnetwork. Default-mode functional connectivity is
      influenced by genetic factors that cannot be attributed to anatomic variation or
      a single region within the network. By establishing the heritability of default
      mode functional connectivity, this experiment provides the obligatory evidence
      required before these measures can be considered as endophenotypes for
      psychiatric or neurological illnesses or to identify genes influencing intrinsic
      brain function.

PMID- 20133825
TI  - Sources, sinks, and drains in double breeding bird species?

PMID- 20133826
TI  - The long-awaited demonstration of protein pyrophosphorylation by IP7 in vivo?

PMID- 20133827
TI  - The risk of a wrong conclusion: on testosterone and gender differences in risk
      aversion and career choices.

PMID- 20133828
TI  - Metal ions as matchmakers for proteins.

PMID- 20133829
TI  - EXTra hit for mouse osteochondroma.

PMID- 20133830
TI  - More than one way to blanch a lizard.

PMID- 20133831
TI  - Permeation mechanism in voltage-activated proton channels: a new glimpse.

PMID- 20133832
TI  - An in vivo demonstration of functional G protein-coupled receptor dimers.

PMID- 20133833
TI  - An impossibility theorem for price-adjustment mechanisms.
AB  - We show that there is no discrete-time price-adjustment mechanism (any process
      that at each period looks at the history of prices and excess demands and updates
      the prices) such that for any market (a set of goods and consumers with
      endowments and strictly concave utilities) the price-adjustment mechanism will
      achieve excess demands that are at most an epsilon fraction of the total supply
      within a number of periods that is polynomial in the number of goods and
      1/epsilon. This holds even if one restricts markets so that excess demand
      functions are differentiable with derivatives bounded by a small constant. For
      the convergence time to the actual price equilibrium, we show by a different
      method a stronger result: Even in the case of three goods with a unique price
      equilibrium, there is no function of epsilon that bounds the number of periods
      needed by a price-adjustment mechanism to arrive at a set of prices that is
      epsilon-close to the equilibrium.

PMID- 20133834
TI  - Female teachers' math anxiety affects girls' math achievement.
AB  - People's fear and anxiety about doing math--over and above actual math ability-
      can be an impediment to their math achievement. We show that when the math
      anxious individuals are female elementary school teachers, their math anxiety
      carries negative consequences for the math achievement of their female students.
      Early elementary school teachers in the United States are almost exclusively
      female (>90%), and we provide evidence that these female teachers' anxieties
      relate to girls' math achievement via girls' beliefs about who is good at math.
      First- and second-grade female teachers completed measures of math anxiety. The
      math achievement of the students in these teachers' classrooms was also assessed.
      There was no relation between a teacher's math anxiety and her students' math
      achievement at the beginning of the school year. By the school year's end,
      however, the more anxious teachers were about math, the more likely girls (but
      not boys) were to endorse the commonly held stereotype that "boys are good at
      math, and girls are good at reading" and the lower these girls' math achievement.
      Indeed, by the end of the school year, girls who endorsed this stereotype had
      significantly worse math achievement than girls who did not and than boys
      overall. In early elementary school, where the teachers are almost all female,
      teachers' math anxiety carries consequences for girls' math achievement by
      influencing girls' beliefs about who is good at math.

PMID- 20133835
TI  - MicroRNA let-7b regulates neural stem cell proliferation and differentiation by
      targeting nuclear receptor TLX signaling.
AB  - Neural stem cell self-renewal and differentiation is orchestrated by precise
      control of gene expression involving nuclear receptor TLX. Let-7b, a member of
      the let-7 microRNA family, is expressed in mammalian brains and exhibits
      increased expression during neural differentiation. However, the role of let-7b
      in neural stem cell proliferation and differentiation remains unknown. Here we
      show that let-7b regulates neural stem cell proliferation and differentiation by
      targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1.
      Overexpression of let-7b led to reduced neural stem cell proliferation and
      increased neural differentiation, whereas antisense knockdown of let-7b resulted
      in enhanced proliferation of neural stem cells. Moreover, in utero
      electroporation of let-7b to embryonic mouse brains led to reduced cell cycle
      progression in neural stem cells. Introducing an expression vector of Tlx or
      cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced
      proliferation deficiency, suggesting that both TLX and cyclin D1 are important
      targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b,
      by targeting TLX and cyclin D1, establishes an efficient strategy to control
      neural stem cell proliferation and differentiation.

PMID- 20133836
TI  - Nanowire transistor arrays for mapping neural circuits in acute brain slices.
AB  - Revealing the functional connectivity in natural neuronal networks is central to
      understanding circuits in the brain. Here, we show that silicon nanowire field
      effect transistor (Si NWFET) arrays fabricated on transparent substrates can be
      reliably interfaced to acute brain slices. NWFET arrays were readily designed to
      record across a wide range of length scales, while the transparent device chips
      enabled imaging of individual cell bodies and identification of areas of healthy
      neurons at both upper and lower tissue surfaces. Simultaneous NWFET and patch
      clamp studies enabled unambiguous identification of action potential signals,
      with additional features detected at earlier times by the nanodevices. NWFET
      recording at different positions in the absence and presence of synaptic and ion
      channel blockers enabled assignment of these features to presynaptic firing and
      postsynaptic depolarization from regions either close to somata or abundant in
      dendritic projections. In all cases, the NWFET signal amplitudes were from 0.3-3
      mV. In contrast to conventional multielectrode array measurements, the small
      active surface of the NWFET devices, approximately 0.06 microm(2), provides
      highly localized multiplexed measurements of neuronal activities with
      demonstrated sub-millisecond temporal resolution and, significantly, better than
      30 microm spatial resolution. In addition, multiplexed mapping with 2D NWFET
      arrays revealed spatially heterogeneous functional connectivity in the olfactory
      cortex with a resolution surpassing substantially previous electrical recording
      techniques. Our demonstration of simultaneous high temporal and spatial
      resolution recording, as well as mapping of functional connectivity, suggest that
      NWFETs can become a powerful platform for studying neural circuits in the brain.

PMID- 20133837
TI  - The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase
      isoform expression and cell metabolism.
AB  - Cancer cells preferentially metabolize glucose by aerobic glycolysis,
      characterized by increased lactate production. This distinctive metabolism
      involves expression of the embryonic M2 isozyme of pyruvate kinase, in contrast
      to the M1 isozyme normally expressed in differentiated cells, and it confers a
      proliferative advantage to tumor cells. The M1 and M2 pyruvate-kinase isozymes
      are expressed from a single gene through alternative splicing of a pair of
      mutually exclusive exons. We measured the expression of M1 and M2 mRNA and
      protein isoforms in mouse tissues, tumor cell lines, and during terminal
      differentiation of muscle cells, and show that alternative splicing regulation is
      sufficient to account for the levels of expressed protein isoforms. We further
      show that the M1-specific exon is actively repressed in cancer-cell lines-
      although some M1 mRNA is expressed in cell lines derived from brain tumors--and
      demonstrate that the related splicing repressors hnRNP A1 and A2, as well as the
      polypyrimidine-tract-binding protein PTB, contribute to this control.
      Downregulation of these splicing repressors in cancer-cell lines using shRNAs
      rescues M1 isoform expression and decreases the extent of lactate production.
      These findings extend the links between alternative splicing and cancer, and
      begin to define some of the factors responsible for the switch to aerobic
      glycolysis.

PMID- 20133838
TI  - Direct assignment of EPR spectra to structurally defined iron-sulfur clusters in
      complex I by double electron-electron resonance.
AB  - In oxidative phosphorylation, complex I (NADH:quinone oxidoreductase) couples
      electron transfer to proton translocation across an energy-transducing membrane.
      Complex I contains a flavin mononucleotide to oxidize NADH, and an unusually long
      series of iron-sulfur (FeS) clusters, in several subunits, to transfer the
      electrons to quinone. Understanding coupled electron transfer in complex I
      requires a detailed knowledge of the properties of individual clusters and of the
      cluster ensemble, and so it requires the correlation of spectroscopic and
      structural data: This has proved a challenging task. EPR studies on complex I
      from Bos taurus have established that EPR signals N1b, N2 and N3 arise,
      respectively, from the 2Fe cluster in the 75 kDa subunit, and from 4Fe clusters
      in the PSST and 51 kDa subunits (positions 2, 7, and 1 along the seven-cluster
      chain extending from the flavin). The other clusters have either evaded detection
      or definitive signal assignments have not been established. Here, we combine
      double electron-electron resonance (DEER) spectroscopy on B. taurus complex I
      with the structure of the hydrophilic domain of Thermus thermophilus complex I.
      By considering the magnetic moments of the clusters and the orientation
      selectivity of the DEER experiment explicitly, signal N4 is assigned to the first
      4Fe cluster in the TYKY subunit (position 5), and N5 to the all-cysteine ligated
      4Fe cluster in the 75 kDa subunit (position 3). The implications of our
      assignment for the mechanisms of electron transfer and energy transduction by
      complex I are discussed.

PMID- 20133839
TI  - Mechanism of amyloid plaque formation suggests an intracellular basis of Abeta
      pathogenicity.
AB  - The formation of extracellular amyloid plaques is a common patho-biochemical
      event underlying several debilitating human conditions, including Alzheimer's
      disease (AD). Considerable evidence implies that AD damage arises primarily from
      small oligomeric amyloid forms of Abeta peptide, but the precise mechanism of
      pathogenicity remains to be established. Using a cell culture system that
      reproducibly leads to the formation of Alzheimer's Abeta amyloid plaques, we show
      here that the formation of a single amyloid plaque represents a template
      dependent process that critically involves the presence of endocytosis- or
      phagocytosis-competent cells. Internalized Abeta peptide becomes sorted to
      multivesicular bodies where fibrils grow out, thus penetrating the vesicular
      membrane. Upon plaque formation, cells undergo cell death and intracellular
      amyloid structures become released into the extracellular space. These data imply
      a mechanism where the pathogenic activity of Abeta is attributed, at least in
      part, to intracellular aggregates.

PMID- 20133840
TI  - Structural insights into phosphoinositide 3-kinase activation by the influenza A
      virus NS1 protein.
AB  - Seasonal epidemics and periodic worldwide pandemics caused by influenza A viruses
      are of continuous concern. The viral nonstructural (NS1) protein is a
      multifunctional virulence factor that antagonizes several host innate immune
      defenses during infection. NS1 also directly stimulates class IA phosphoinositide
      3-kinase (PI3K) signaling, an essential cell survival pathway commonly mutated in
      human cancers. Here, we present a 2.3-A resolution crystal structure of the NS1
      effector domain in complex with the inter-SH2 (coiled-coil) domain of p85beta, a
      regulatory subunit of PI3K. Our data emphasize the remarkable isoform specificity
      of this interaction, and provide insights into the mechanism by which NS1
      activates the PI3K (p85beta:p110) holoenzyme. A model of the NS1:PI3K
      heterotrimeric complex reveals that NS1 uses the coiled-coil as a structural
      tether to sterically prevent normal inhibitory contacts between the N-terminal
      SH2 domain of p85beta and the p110 catalytic subunit. Furthermore, in this model,
      NS1 makes extensive contacts with the C2/kinase domains of p110, and a small
      acidic alpha-helix of NS1 sits adjacent to the highly basic activation loop of
      the enzyme. During infection, a recombinant influenza A virus expressing NS1 with
      charge-disruption mutations in this acidic alpha-helix is unable to stimulate the
      production of phosphatidylinositol 3,4,5-trisphosphate or the phosphorylation of
      Akt. Despite this, the charge-disruption mutations in NS1 do not affect its
      ability to interact with the p85beta inter-SH2 domain in vitro. Overall, these
      data suggest that both direct binding of NS1 to p85beta (resulting in
      repositioning of the N-terminal SH2 domain) and possible NS1:p110 contacts
      contribute to PI3K activation.

PMID- 20133841
TI  - Implications for the active form of human insulin based on the structural
      convergence of highly active hormone analogues.
AB  - Insulin is a key protein hormone that regulates blood glucose levels and, thus,
      has widespread impact on lipid and protein metabolism. Insulin action is
      manifested through binding of its monomeric form to the Insulin Receptor (IR). At
      present, however, our knowledge about the structural behavior of insulin is based
      upon inactive, multimeric, and storage-like states. The active monomeric
      structure, when in complex with the receptor, must be different as the residues
      crucial for the interactions are buried within the multimeric forms. Although the
      exact nature of the insulin's induced-fit is unknown, there is strong evidence
      that the C-terminal part of the B-chain is a dynamic element in insulin
      activation and receptor binding. Here, we present the design and analysis of
      highly active (200-500%) insulin analogues that are truncated at residue 26 of
      the B-chain (B(26)). They show a structural convergence in the form of a new beta
      turn at B(24)-B(26). We propose that the key element in insulin's transition,
      from an inactive to an active state, may be the formation of the beta-turn at
      B(24)-B(26) associated with a trans to cis isomerisation at the B(25)-B(26)
      peptide bond. Here, this turn is achieved with N-methylated L-amino acids
      adjacent to the trans to cis switch at the B(25)-B(26) peptide bond or by the
      insertion of certain D-amino acids at B(26). The resultant conformational changes
      unmask previously buried amino acids that are implicated in IR binding and
      provide structural details for new approaches in rational design of ligands
      effective in combating diabetes.

PMID- 20133842
TI  - Crystal structure of the DNA-recognition component of the bacterial virus Sf6
      genome-packaging machine.
AB  - In herpesviruses and many bacterial viruses, genome-packaging is a precisely
      mediated process fulfilled by a virally encoded molecular machine called
      terminase that consists of two protein components: A DNA-recognition component
      that defines the specificity for packaged DNA, and a catalytic component that
      provides energy for the packaging reaction by hydrolyzing ATP. The terminase
      docks onto the portal protein complex embedded in a single vertex of a preformed
      viral protein shell called procapsid, and pumps the viral DNA into the procapsid
      through a conduit formed by the portal. Here we report the 1.65 A resolution
      structure of the DNA-recognition component gp1 of the Shigella bacteriophage Sf6
      genome-packaging machine. The structure reveals a ring-like octamer formed by
      interweaved protein monomers with a highly extended fold, embracing a tunnel
      through which DNA may be translocated. The N-terminal DNA-binding domains form
      the peripheral appendages surrounding the octamer. The central domain contributes
      to oligomerization through interactions of bundled helices. The C-terminal domain
      forms a barrel with parallel beta-strands. The structure reveals a common scheme
      for oligomerization of terminase DNA-recognition components, and provides
      insights into the role of gp1 in formation of the packaging-competent terminase
      complex and assembly of the terminase with the portal, in which ring-like protein
      oligomers stack together to form a continuous channel for viral DNA
      translocation.

PMID- 20133843
TI  - Methionine oxidation induces amyloid fibril formation by full-length
      apolipoprotein A-I.
AB  - Apolipoprotein A-I (apoA-I) is the major protein component of HDL, where it plays
      an important role in cholesterol transport. The deposition of apoA-I derived
      amyloid is associated with various hereditary systemic amyloidoses and
      atherosclerosis; however, very little is known about the mechanism of apoA-I
      amyloid formation. Methionine residues in apoA-I are oxidized via several
      mechanisms in vivo to form methionine sulfoxide (MetO), and significant levels of
      methionine oxidized apoA-I (MetO-apoA-I) are present in normal human serum. We
      investigated the effect of methionine oxidation on the structure, stability, and
      aggregation of full-length, lipid-free apoA-I. Circular dichrosim spectroscopy
      showed that oxidation of all three methionine residues in apoA-I caused partial
      unfolding of the protein and decreased its thermal stability, reducing the
      melting temperature (T(m)) from 58.7 degrees C for native apoA-I to 48.2 degrees
      C for MetO-apoA-I. Analytical ultracentrifugation revealed that methionine
      oxidation inhibited the native self association of apoA-I to form dimers and
      tetramers. Incubation of MetO-apoA-I for extended periods resulted in aggregation
      of the protein, and these aggregates bound Thioflavin T and Congo Red. Inspection
      of the aggregates by electron microscopy revealed fibrillar structures with a
      ribbon-like morphology, widths of approximately 11 nm, and lengths of up to
      several microns. X-ray fibre diffraction studies of the fibrils revealed a
      diffraction pattern with orthogonal peaks at spacings of 4.64 A and 9.92 A,
      indicating a cross-beta amyloid structure. This systematic study of fibril
      formation by full-length apoA-I represents the first demonstration that
      methionine oxidation can induce amyloid fibril formation.

PMID- 20133844
TI  - Protein interactions and ligand binding: from protein subfamilies to functional
      specificity.
AB  - The divergence accumulated during the evolution of protein families translates
      into their internal organization as subfamilies, and it is directly reflected in
      the characteristic patterns of differentially conserved residues. These
      specifically conserved positions in protein subfamilies are known as "specificity
      determining positions" (SDPs). Previous studies have limited their analysis to
      the study of the relationship between these positions and ligand-binding
      specificity, demonstrating significant yet limited predictive capacity. We have
      systematically extended this observation to include the role of differential
      protein interactions in the segregation of protein subfamilies and explored in
      detail the structural distribution of SDPs at protein interfaces. Our results
      show the extensive influence of protein interactions in the evolution of protein
      families and the widespread association of SDPs with protein interfaces. The
      combined analysis of SDPs in interfaces and ligand-binding sites provides a more
      complete picture of the organization of protein families, constituting the
      necessary framework for a large scale analysis of the evolution of protein
      function.

PMID- 20133845
TI  - Quaternary dynamics and plasticity underlie small heat shock protein chaperone
      function.
AB  - Small Heat Shock Proteins (sHSPs) are a diverse family of molecular chaperones
      that prevent protein aggregation by binding clients destabilized during cellular
      stress. Here we probe the architecture and dynamics of complexes formed between
      an oligomeric sHSP and client by employing unique mass spectrometry strategies.
      We observe over 300 different stoichiometries of interaction, demonstrating that
      an ensemble of structures underlies the protection these chaperones confer to
      unfolding clients. This astonishing heterogeneity not only makes the system quite
      distinct in behavior to ATP-dependent chaperones, but also renders it intractable
      by conventional structural biology approaches. We find that thermally regulated
      quaternary dynamics of the sHSP establish and maintain the plasticity of the
      system. This extends the paradigm that intrinsic dynamics are crucial to protein
      function to include equilibrium fluctuations in quaternary structure, and
      suggests they are integral to the sHSPs' role in the cellular protein homeostasis
      network.

PMID- 20133846
TI  - Full distance-resolved folding energy landscape of one single protein molecule.
AB  - Kinetic bulk and single molecule folding experiments characterize barrier
      properties but the shape of folding landscapes between barrier top and native
      state is difficult to access. Here, we directly extract the full free energy
      landscape of a single molecule of the GCN4 leucine zipper using dual beam optical
      tweezers. To this end, we use deconvolution force spectroscopy to follow an
      individual molecule's trajectory with high temporal and spatial resolution. We
      find a heterogeneous energy landscape of the GCN4 leucine zipper domain. The
      energy profile is divided into two stable C-terminal heptad repeats and two less
      stable repeats at the N-terminus. Energies and transition barrier positions were
      confirmed by single molecule kinetic analysis. We anticipate that deconvolution
      sampling is a powerful tool for the model-free investigation of protein energy
      landscapes.

PMID- 20133847
TI  - Myosin Va cooperates with PKA RIalpha to mediate maintenance of the endplate in
      vivo.
AB  - Myosin V motor proteins facilitate recycling of synaptic receptors, including
      AMPA and acetylcholine receptors, in central and peripheral synapses,
      respectively. To shed light on the regulation of receptor recycling, we employed
      in vivo imaging of mouse neuromuscular synapses. We found that myosin Va
      cooperates with PKA on the postsynapse to maintain size and integrity of the
      synapse; this cooperation also regulated the lifetime of acetylcholine receptors.
      Myosin Va and PKA colocalized in subsynaptic enrichments. These accumulations
      were crucial for synaptic integrity and proper cAMP signaling, and were dependent
      on AKAP function, myosin Va, and an intact actin cytoskeleton. The neuropeptide
      and cAMP agonist, calcitonin-gene related peptide, rescued fragmentation of
      synapses upon denervation. We hypothesize that neuronal ligands trigger local
      activation of PKA, which in turn controls synaptic integrity and turnover of
      receptors. To this end, myosin Va mediates correct positioning of PKA in a
      postsynaptic microdomain, presumably by tethering PKA to the actin cytoskeleton.

PMID- 20133848
TI  - Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor
      progression.
AB  - As the result of genetic alterations and tumor hypoxia, many cancer cells avidly
      take up glucose and generate lactate through lactate dehydrogenase A (LDHA),
      which is encoded by a target gene of c-Myc and hypoxia-inducible factor (HIF-1).
      Previous studies with reduction of LDHA expression indicate that LDHA is involved
      in tumor initiation, but its role in tumor maintenance and progression has not
      been established. Furthermore, how reduction of LDHA expression by interference
      or antisense RNA inhibits tumorigenesis is not well understood. Here, we report
      that reduction of LDHA by siRNA or its inhibition by a small-molecule inhibitor
      (FX11 [3-dihydroxy-6-methyl-7-(phenylmethyl)-4-propylnaphthalene-1-carboxylic
      acid]) reduced ATP levels and induced significant oxidative stress and cell death
      that could be partially reversed by the antioxidant N-acetylcysteine.
      Furthermore, we document that FX11 inhibited the progression of sizable human
      lymphoma and pancreatic cancer xenografts. When used in combination with the
      NAD(+) synthesis inhibitor FK866, FX11 induced lymphoma regression. Hence,
      inhibition of LDHA with FX11 is an achievable and tolerable treatment for LDHA
      dependent tumors. Our studies document a therapeutical approach to the Warburg
      effect and demonstrate that oxidative stress and metabolic phenotyping of cancers
      are critical aspects of cancer biology to consider for the therapeutical
      targeting of cancer energy metabolism.

PMID- 20133849
TI  - A circadian clock in Saccharomyces cerevisiae.
AB  - Circadian timing is a fundamental biological process, underlying cellular
      physiology in animals, plants, fungi, and cyanobacteria. Circadian clocks
      organize gene expression, metabolism, and behavior such that they occur at
      specific times of day. The biological clocks that orchestrate these daily changes
      confer a survival advantage and dominate daily behavior, for example, waking us
      in the morning and helping us to sleep at night. The molecular mechanism of
      circadian clocks has been sketched out in genetic model systems from prokaryotes
      to humans, revealing a combination of transcriptional and posttranscriptional
      pathways, but the clock mechanism is far from solved. Although Saccharomyces
      cerevisiae is among the most powerful genetic experimental systems and, as such,
      could greatly contribute to our understanding of cellular timing, it still
      remains absent from the repertoire of circadian model organisms. Here, we use
      continuous cultures of yeast, establishing conditions that reveal characteristic
      clock properties similar to those described in other species. Our results show
      that metabolism in yeast shows systematic circadian entrainment, responding to
      cycle length and zeitgeber (stimulus) strength, and a (heavily damped) free
      running rhythm. Furthermore, the clock is obvious in a standard, haploid,
      auxotrophic strain, opening the door for rapid progress into cellular clock
      mechanisms.

PMID- 20133850
TI  - Bombyx prothoracicostatic peptides activate the sex peptide receptor to regulate
      ecdysteroid biosynthesis.
AB  - Insect molting and metamorphosis are induced by steroid hormones named
      ecdysteroids, whose production is regulated by various neuropeptides. We cloned
      the gene and analyzed the expression of the prothoracicostatic peptide, a unique
      neuropeptide shown to suppress the production of ecdysteroids in the prothoracic
      gland of the silkworm, Bombyx mori. We also characterized a Bombyx G protein
      coupled receptor, which has previously been identified as an ortholog of the
      Drosophila sex peptide receptor, as a functional prothoracicostatic peptide
      receptor. This receptor responded specifically to the prothoracicostatic peptides
      when examined using a heterologous expression system. The receptor was highly
      expressed in the prothoracic gland on the day before each larval and pupal
      ecdysis, when prothoracicostatic peptides are synthesized at a high level in the
      epiproctodeal glands. These results suggest that the sex peptide receptor
      functions as a prothoracicostatic peptide receptor in Bombyx and that the
      peripheral neurosecretory cells as well as the central neuroendocrine system play
      stage-specific roles in regulating ecdysteroidogenesis.

PMID- 20133851
TI  - Epibranchial ganglia orchestrate the development of the cranial neurogenic crest.
AB  - The wiring of the nervous system arises from extensive directional migration of
      neuronal cell bodies and growth of processes that, somehow, end up forming
      functional circuits. Thus far, this feat of biological engineering appears to
      rely on sequences of pathfinding decisions upon local cues, each with little
      relationship to the anatomical and physiological outcome. Here, we uncover a
      straightforward cellular mechanism for circuit building whereby a neuronal type
      directs the development of its future partners. We show that visceral afferents
      of the head (that innervate taste buds) provide a scaffold for the establishment
      of visceral efferents (that innervate salivatory glands and blood vessels). In
      embryological terms, sensory neurons derived from an epibranchial placode--that
      we show to develop largely independently from the neural crest--guide the
      directional outgrowth of hindbrain visceral motoneurons and control the formation
      of neural crest-derived parasympathetic ganglia.

PMID- 20133852
TI  - Plants cause ecosystem nutrient depletion via the interruption of bird-derived
      spatial subsidies.
AB  - Plant introductions and subsequent community shifts are known to affect nutrient
      cycling, but most such studies have focused on nutrient enrichment effects. The
      nature of plant-driven nutrient depletions and the mechanisms by which these
      might occur are relatively poorly understood. In this study we demonstrate that
      the proliferation of the commonly introduced coconut palm, Cocos nucifera,
      interrupts the flow of allochthonous marine subsidies to terrestrial ecosystems
      via an indirect effect: impact on birds. Birds avoid nesting or roosting in C.
      nucifera, thus reducing the critical nutrient inputs they bring from the marine
      environment. These decreases in marine subsidies then lead to reductions in
      available soil nutrients, decreases in leaf nutrient quality, diminished leaf
      palatability, and reduced herbivory. This nutrient depletion pathway contrasts
      the more typical patterns of nutrient enrichment that follow plant species
      introductions. Research on the effects of spatial subsidy disruptions on
      ecosystems has not yet examined interruptions driven by changes within the
      recipient community, such as plant community shifts. The ubiquity of coconut palm
      introductions across the tropics and subtropics makes these observations
      particularly noteworthy. Equally important, the case of C. nucifera provides a
      strong demonstration of how plant community changes can dramatically impact the
      supply of allochthonous nutrients and thereby reshape energy flow in ecosystems.

PMID- 20133853
TI  - A dinoflagellate exploits toxins to immobilize prey prior to ingestion.
AB  - Toxins produced by the harmful algal bloom (HAB) forming, mixotrophic
      dinoflagellate Karlodinium veneficum have long been associated with fish kills.
      To date, the perceived ecological role for toxins has been relief from grazing
      pressures. Here, we demonstrate that karlotoxins also serve as a predation
      instrument. Using high-speed holographic microscopy, we measure the swimming
      behavior of several toxic and nontoxic strains of K. veneficum and their prey,
      Storeatula major, within dense suspensions. The selected strains produce toxins
      with varying potency and dosages, including a nontoxic one. Results clearly show
      that mixing the prey with the predatory, toxic strains causes prey immobilization
      at rates that are consistent with the karlotoxins' potency and dosage. Even prey
      cells that continue swimming slow down after exposure to toxic predators. The
      swimming characteristics of predators vary substantially in pure suspensions, as
      quantified by their velocity, radii of helical trajectories, and direction of
      helical rotation. When mixed with prey, all toxic strains that are involved in
      predation slow down. Furthermore, they substantially reduced their predominantly
      vertical migration, presumably to remain in the vicinity of their prey.
      Conversely, the nontoxic control strain does not alter its swimming and does not
      affect prey behavior. In separate experiments, we show that exposing prey to
      exogenous toxins also causes prey immobilization at rates consistent with
      potency. Clearly, the toxic predatory strains use karlotoxins as a means of
      stunning their prey, before ingesting it. These findings add a substantiated
      critical understanding for why some HAB species produce such complex toxin
      molecules.

PMID- 20133854
TI  - Compounded effects of climate change and habitat alteration shift patterns of
      butterfly diversity.
AB  - Climate change and habitat destruction have been linked to global declines in
      vertebrate biodiversity, including mammals, amphibians, birds, and fishes.
      However, invertebrates make up the vast majority of global species richness, and
      the combined effects of climate change and land use on invertebrates remain
      poorly understood. Here we present 35 years of data on 159 species of butterflies
      from 10 sites along an elevational gradient spanning 0-2,775 m in a biodiversity
      hotspot, the Sierra Nevada Mountains of Northern California. Species richness has
      declined at half of the sites, with the most severe reductions at the lowest
      elevations, where habitat destruction is greatest. At higher elevations, we
      observed clear upward shifts in the elevational ranges of species, consistent
      with the influence of global warming. Taken together, these long-term data reveal
      the interacting negative effects of human-induced changes on both the climate and
      habitat available to butterfly species in California. Furthermore, the decline of
      ruderal, disturbance-associated species indicates that the traditional focus of
      conservation efforts on more specialized and less dispersive species should be
      broadened to include entire faunas when estimating and predicting the effects of
      pervasive stressors.

PMID- 20133855
TI  - Resource limitation is a driver of local adaptation in mycorrhizal symbioses.
AB  - Symbioses may be important mechanisms of plant adaptation to their environment.
      We conducted a reciprocal inoculation experiment to test the hypothesis that soil
      fertility is a key driver of local adaptation in arbuscular mycorrhizal (AM)
      symbioses. Ecotypes of Andropogon gerardii from phosphorus-limited and nitrogen
      limited grasslands were grown with all possible "home and away" combinations of
      soils and AM fungal communities. Our results indicate that Andropogon ecotypes
      adapt to their local soil and indigenous AM fungal communities such that
      mycorrhizal exchange of the most limiting resource is maximized. Grasses grown in
      home soil and inoculated with home AM fungi produced more arbuscules (symbiotic
      exchange structures) in their roots than those grown in away combinations. Also,
      regardless of the host ecotype, AM fungi produced more extraradical hyphae in
      their home soil, and locally adapted AM fungi were, therefore, able to sequester
      more carbon compared with nonlocal fungi. Locally adapted mycorrhizal
      associations were more mutualistic in the two phosphorus-limited sites and less
      parasitic at the nitrogen-limited site compared with novel combinations of
      plants, fungi, and soils. To our knowledge, these findings provide the strongest
      evidence to date that resource availability generates evolved geographic
      structure in symbioses among plants and soil organisms. Thus, edaphic origin of
      AM fungi should be considered when managing for their benefits in agriculture,
      ecosystem restoration, and soil-carbon sequestration.

PMID- 20133856
TI  - Corn content of French fry oil from national chain vs. small business
      restaurants.
AB  - Several issues, ranging from sustainability to health, may interest the consumers
      in the corn content of their food. However, because restaurants are excluded from
      the Nutrition Labeling and Education Act of 1990, national chain restaurants
      provide nonspecific ingredient information and small businesses supply none. We
      measured the carbon isotope composition of fry oil in French fries purchased from
      68 (67%) of the 101 national chain fast food restaurants on Oahu (i.e.,
      McDonald's, Burger King, Wendy's, Arby's, and Jack in the Box), and paired this
      with a similar number of small businesses (n = 66) to calculate minimum percent
      contribution of corn to total fry oil. We found that the majority (69%) of the
      national chain restaurants served fries containing corn oil, whereas this was
      true for only a minority (20%) of the small businesses. Corn oil is more
      expensive than soybean oil (for example) when purchased from a small business
      supplier, suggesting that large-scale corporate agreements are necessary to make
      corn oil frying cost-effective. When considering French fry oil along with corn
      fed beef and chicken, as well as high-fructose corn syrup-sweetened soda, we see
      the pervasive influence of corn as an ingredient in national chain fast food.

PMID- 20133857
TI  - Rapid evolution of stability and productivity at the origin of a microbial
      mutualism.
AB  - Mutualistic interactions are taxonomically and functionally diverse. Despite
      their ubiquity, however, the basic ecological and evolutionary processes
      underlying their origin and maintenance are poorly understood. A major reason for
      this is the lack of an experimentally tractable model system. We examine the
      evolution of an experimentally imposed obligate mutualism between sulfate
      reducing and methanogenic microorganisms that have no known history of previous
      interaction. Twenty-four independent pairings (cocultures) of the bacterium
      Desulfovibrio vulgaris and the archaeon Methanococcus maripaludis were
      established and followed for 300 community doublings in two environments, one
      allowing for the development of a heterogeneous distribution of resources and the
      other not. Evolved cocultures grew up to 80% faster and were up to 30% more
      productive (biomass yield per mole of substrate) than the ancestors. The
      evolutionary process was marked by periods of significant instability leading to
      extinction of two of the cocultures, but it resulted in more stable, efficient,
      and productive mutualisms for most replicated pairings. Comparisons of evolved
      cocultures with those assembled from one evolved mutualist and one ancestral
      mutualist showed that evolution of both species contributed to improved
      productivity. Surprisingly, however, overall improvements in growth rate and
      yield were less than the sum of the individual contributions, suggesting
      antagonistic interactions between mutations from the coevolved populations.
      Physical constraints on the transfer of metabolites in the evolution environment
      affected the evolution of M. maripaludis, but not of D. vulgaris. Together, these
      results demonstrate that challenges can imperil nascent obligate mutualisms and
      demonstrate the evolutionary responses that enable their persistence and future
      evolution.

PMID- 20133858
TI  - An end-joining repair mechanism in Escherichia coli.
AB  - Bridging broken DNA ends via nonhomologous end-joining (NHEJ) contributes to the
      evolution and stability of eukaryote genomes. Although some bacteria possess a
      simplified NHEJ mechanism, the human commensal Escherichia coli is thought to
      rely exclusively on homology-directed mechanisms to repair DNA double-strand
      breaks (DSBs). We show here that laboratory and pathogenic E. coli strains
      possess a distinct end-joining activity that repairs DSBs and generates genome
      rearrangements. This mechanism, named alternative end-joining (A-EJ), does not
      rely on the key NHEJ proteins Ku and Ligase-D which are absent in E. coli.
      Differently from classical NHEJ, A-EJ is characterized by extensive end-resection
      largely due to RecBCD, by overwhelming usage of microhomology and extremely rare
      DNA synthesis. We also show that A-EJ is dependent on the essential Ligase-A and
      independent on Ligase-B. Importantly, mutagenic repair requires a functional
      Ligase-A. Although generally mutagenic, accurate A-EJ also occurs and is frequent
      in some pathogenic bacteria. Furthermore, we show the acquisition of an
      antibiotic-resistance gene via A-EJ, refuting the notion that bacteria gain
      exogenous sequences only by recombination-dependent mechanisms. This finding
      demonstrates that E. coli can integrate unrelated, nonhomologous exogenous
      sequences by end-joining and it provides an alternative strategy for horizontal
      gene transfer in the bacterial genome. Thus, A-EJ contributes to bacterial genome
      evolution and adaptation to environmental challenges. Interestingly, the key
      features of A-EJ also appear in A-NHEJ, an alternative end-joining mechanism
      implicated in chromosomal translocations associated with human malignancies, and
      we propose that this mutagenic repair might have originated in bacteria.

PMID- 20133859
TI  - Mobile elements reveal small population size in the ancient ancestors of Homo
      sapiens.
AB  - The genealogies of different genetic loci vary in depth. The deeper the
      genealogy, the greater the chance that it will include a rare event, such as the
      insertion of a mobile element. Therefore, the genealogy of a region that contains
      a mobile element is on average older than that of the rest of the genome. In a
      simple demographic model, the expected time to most recent common ancestor
      (TMRCA) is doubled if a rare insertion is present. We test this expectation by
      examining single nucleotide polymorphisms around polymorphic Alu insertions from
      two completely sequenced human genomes. The estimated TMRCA for regions
      containing a polymorphic insertion is two times larger than the genomic average
      (P < <10(-30)), as predicted. Because genealogies that contain polymorphic mobile
      elements are old, they are shaped largely by the forces of ancient population
      history and are insensitive to recent demographic events, such as bottlenecks and
      expansions. Remarkably, the information in just two human DNA sequences provides
      substantial information about ancient human population size. By comparing the
      likelihood of various demographic models, we estimate that the effective
      population size of human ancestors living before 1.2 million years ago was
      18,500, and we can reject all models where the ancient effective population size
      was larger than 26,000. This result implies an unusually small population for a
      species spread across the entire Old World, particularly in light of the
      effective population sizes of chimpanzees (21,000) and gorillas (25,000), which
      each inhabit only one part of a single continent.

PMID- 20133860
TI  - bZIP transcription factor zip-2 mediates an early response to Pseudomonas
      aeruginosa infection in Caenorhabditis elegans.
AB  - Very little is known about how animals discriminate pathogens from innocuous
      microbes. To address this question, we examined infection-response gene induction
      in the nematode Caenorhabditis elegans. We focused on genes that are induced in
      C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but
      are not induced by an isogenic attenuated gacA mutant. Most of these genes are
      induced independently of known immunity pathways. We generated a GFP reporter for
      one of these genes, infection response gene 1 (irg-1), which is induced strongly
      by wild-type P. aeruginosa strain PA14, but not by other C. elegans pathogens or
      by other wild-type P. aeruginosa strains that are weakly pathogenic to C.
      elegans. To identify components of the pathway that induces irg-1 in response to
      infection, we performed an RNA interference screen of C. elegans transcription
      factors. This screen identified zip-2, a bZIP transcription factor that is
      required for inducing irg-1, as well as several other genes, and is important for
      defense against infection by P. aeruginosa. These data indicate that zip-2 is
      part of a specialized pathogen response pathway that is induced by virulent
      strains of P. aeruginosa and provides defense against this pathogen.

PMID- 20133861
TI  - Nuclear location of an endogenously expressed antigen, EBNA1, restricts access to
      macroautophagy and the range of CD4 epitope display.
AB  - Whereas exogenously acquired proteins are the major source of antigens feeding
      the MHC class II pathway in antigen-presenting cells, some endogenously expressed
      antigens also access that pathway but the rules governing such access are poorly
      understood. Here we address this using Epstein-Barr virus (EBV)-coded nuclear
      antigen EBNA1, a protein naturally expressed in EBV-infected B lymphoblastoid
      cell lines (LCLs) and a source of multiple CD4(+) T cell epitopes. Using CD4(+) T
      cell clones against three indicator epitopes, we find that two epitopes are
      weakly displayed on the LCL surface whereas the third is undetectable, a pattern
      of limited epitope presentation that is maintained even when nuclear expression
      of EBNA1 is induced to high supraphysiological levels. Inhibitor and siRNA
      studies show that, of the two epitopes weakly presented under these conditions,
      one involves macroautophagy, and the second involves antigen delivery to the MHC
      II pathway by another endogenous route. In contrast, when EBNA1 is expressed as a
      cytoplasmic protein, all three CD4 epitopes are processed and presented much more
      efficiently, and all involve macroautophagy. We conclude that EBNA1's nuclear
      location limits its accessibility to the macroautophagy pathway and, in
      consequence, limits the level and range of EBNA1 CD4 epitopes naturally displayed
      on the infected cell surface.

PMID- 20133862
TI  - IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding
      interaction with IL-2 receptor alpha subunit CD25.
AB  - IL-2 is crucial to T cell homeostasis, especially of CD4(+) T regulatory cells
      and memory CD8(+) cells, as evidenced by vigorous proliferation of these cells in
      vivo following injections of superagonist IL-2/anti-IL-2 antibody complexes. The
      mechanism of IL-2/anti-IL-2 antibody complexes is unknown owing to a lack of
      understanding of IL-2 homeostasis. We show that IL-2 receptor alpha (CD25) plays
      a crucial role in IL-2 homeostasis. Thus, prolongation of IL-2 half-life and
      blocking of CD25 using antibodies or CD25-deficient mice led in combination, but
      not alone, to vigorous IL-2-mediated T cell proliferation, similar to IL-2/anti
      IL-2 antibody complexes. These data suggest an unpredicted role for CD25 in IL-2
      homeostasis.

PMID- 20133863
TI  - Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a
      pathway mediated by E2F4 and p130.
AB  - Inhibitors of poly(ADP-ribose) polymerase (PARP) are in clinical trials for
      cancer therapy, on the basis of the role of PARP in recruitment of base excision
      repair (BER) factors to sites of DNA damage. Here we show that PARP inhibition to
      block BER is toxic to hypoxic cancer cells, in which homology-dependent repair
      (HDR) is known to be down-regulated. However, we also report the unexpected
      finding that disruption of PARP, itself, either via chemical PARP inhibitors or
      siRNAs targeted to PARP-1, can inhibit HDR by suppressing expression of BRCA1 and
      RAD51, key factors in HDR of DNA breaks. Mechanistically, PARP inhibition was
      found to cause increased occupancy of the BRCA1 and RAD51 promoters by repressive
      E2F4/p130 complexes, a pathway prevented by expression of HPV E7, which disrupts
      p130 activity, or by siRNAs to knock down p130 expression. Functionally,
      disruption of p130 by E7 expression or by siRNA knockdown also reverses the
      cytotoxicity and radiosensitivity associated with PARP inhibition, suggesting
      that the down-regulation of BRCA1 and RAD51 is central to these effects. Direct
      measurement of HDR using a GFP-based assay demonstrates reduced HDR in cells
      treated with PARP inhibitors. This work identifies a mechanism by which PARP
      regulates DNA repair and suggests new strategies for combination cancer
      therapies.

PMID- 20133864
TI  - Accelerated carcinogenesis following liver regeneration is associated with
      chronic inflammation-induced double-strand DNA breaks.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality
      worldwide and is considered to be the outcome of chronic liver inflammation.
      Currently, the main treatment for HCC is surgical resection. However, survival
      rates are suboptimal partially because of tumor recurrence in the remaining
      liver. Our aim was to understand the molecular mechanisms linking liver
      regeneration under chronic inflammation to hepatic tumorigenesis. Mdr2-KO mice, a
      model of inflammation-associated cancer, underwent partial hepatectomy (PHx),
      which led to enhanced hepatocarcinogenesis. Moreover, liver regeneration in these
      mice was severely attenuated. We demonstrate the activation of the DNA damage
      response machinery and increased genomic instability during early liver
      inflammatory stages resulting in hepatocyte apoptosis, cell-cycle arrest, and
      senescence and suggest their involvement in tumor growth acceleration subsequent
      to PHx. We propose that under the regenerative proliferative stress induced by
      liver resection, the genomic unstable hepatocytes generated during chronic
      inflammation escape senescence and apoptosis and reenter the cell cycle,
      triggering the enhanced tumorigenesis. Thus, we clarify the immediate and long
      term contributions of the DNA damage response to HCC development and recurrence.

PMID- 20133865
TI  - Spatiotemporal controlled delivery of nanoparticles to injured vasculature.
AB  - There are a number of challenges associated with designing nanoparticles for
      medical applications. We define two challenges here: (i) conventional targeting
      against up-regulated cell surface antigens is limited by heterogeneity in
      expression, and (ii) previous studies suggest that the optimal size of
      nanoparticles designed for systemic delivery is approximately 50-150 nm, yet this
      size range confers a high surface area-to-volume ratio, which results in fast
      diffusive drug release. Here, we achieve spatial control by biopanning a phage
      library to discover materials that target abundant vascular antigens exposed in
      disease. Next, we achieve temporal control by designing 60-nm hybrid
      nanoparticles with a lipid shell interface surrounding a polymer core, which is
      loaded with slow-eluting conjugates of paclitaxel for controlled ester hydrolysis
      and drug release over approximately 12 days. The nanoparticles inhibited human
      aortic smooth muscle cell proliferation in vitro and showed greater in vivo
      vascular retention during percutaneous angioplasty over nontargeted controls.
      This nanoparticle technology may potentially be used toward the treatment of
      injured vasculature, a clinical problem of primary importance.

PMID- 20133866
TI  - PAS domain containing chemoreceptor couples dynamic changes in metabolism with
      chemotaxis.
AB  - Chemoreceptors provide sensory specificity and sensitivity that enable motile
      bacteria to seek optimal positions for growth and metabolism in gradients of
      various physicochemical cues. Despite the abundance of chemoreceptors, little is
      known regarding the sensory specificity and the exact contribution of individual
      chemoreceptors to the lifestyle of bacteria. Azospirillum brasilense are motile
      bacteria that can fix atmospheric nitrogen under microaerophilic conditions.
      Here, we characterized a chemoreceptor in this organism, named AerC, which
      functions as a redox sensor that enables the cells to seek microaerophilic
      conditions that support optimum nitrogen fixation. AerC is a representative of a
      widespread class of soluble chemoreceptors that monitor changes in the redox
      status of the electron transport system via the FAD cofactor associated with its
      PAS domains. In A. brasilense, AerC clusters at the cell poles. Its cellular
      localization and contribution to the behavioral response correlate with its
      expression pattern and with changes in the overall cellular FAD content under
      nitrogen-fixing conditions. AerC-mediated energy taxis in A. brasilense prevails
      under conditions of nitrogen fixation, illustrating a strategy by which cells
      optimize chemosensing to signaling cues that directly affect current metabolic
      activities and thus revealing a mechanism by which chemotaxis is coordinated with
      dynamic changes in cell physiology.

PMID- 20133867
TI  - Antibody-mediated enhancement of community-acquired methicillin-resistant
      Staphylococcus aureus infection.
AB  - Community-acquired infections caused by methicillin-resistant Staphylococcus
      aureus (MRSA) expressing the Panton-Valentine leukocidin (PVL) are rampant, but
      the contribution of PVL to bacterial virulence remains controversial. While PVL
      is usually viewed as a cytotoxin, at sublytic amounts it activates protective
      innate immune responses. A leukotoxic effect might predominate in high inoculum
      studies, whereas protective proinflammatory properties might predominate in
      settings with lower bacterial inocula that more closely mimic what initially
      occurs in humans. However, these protective effects might possibly be neutralized
      by antibodies to PVL, which are found in normal human sera and at increased
      levels following PVL(+) S. aureus infections. In a low-inoculum murine skin
      abscess model including a foreign body at the infection site, strains deleted for
      the pvl genes replicated more efficiently within abscesses than isogenic PVL(+)
      strains. Coinfection of mice at separate sites with isogenic PVL(+) and PVL(-)
      MRSA abrogated the differences in bacterial burdens, indicating a systemic effect
      on host innate immunity from production of PVL. Mice given antibody to PVL and
      then infected with seven different PVL(+) strains also had significantly higher
      bacterial counts in abscesses compared with mice given nonimmune serum. Antibody
      to PVL had no effect on MRSA strains that did not produce PVL. In vitro, antibody
      to PVL incapacitated PVL-mediated activation of PMNs, indicating that virulence
      of PVL(+) MRSA is enhanced by the interference of PVL-activated innate immune
      responses. Given the high rates of primary and recurring MRSA infections in
      humans, it appears that antibodies to PVL might contribute to host susceptibility
      to infection.

PMID- 20133868
TI  - T7 phage protein Gp2 inhibits the Escherichia coli RNA polymerase by antagonizing
      stable DNA strand separation near the transcription start site.
AB  - Infection of Escherichia coli by the T7 phage leads to rapid and selective
      inhibition of the host RNA polymerase (RNAP)--a multi-subunit enzyme responsible
      for gene transcription--by a small ( approximately 7 kDa) phage-encoded protein
      called Gp2. Gp2 is also a potent inhibitor of E. coli RNAP in vitro. Here we
      describe the first atomic resolution structure of Gp2, which reveals a distinct
      run of surface-exposed negatively charged amino acid residues on one side of the
      molecule. Our comprehensive mutagenesis data reveal that two conserved arginine
      residues located on the opposite side of Gp2 are important for binding to and
      inhibition of RNAP. Based on a structural model of the Gp2-RNAP complex, we
      propose that inhibition of transcription by Gp2 involves prevention of RNAP
      promoter DNA interactions required for stable DNA strand separation and
      maintenance of the "transcription bubble" near the transcription start site, an
      obligatory step in the formation of a transcriptionally competent promoter
      complex.

PMID- 20133869
TI  - ISG15 conjugation system targets the viral NS1 protein in influenza A virus
      infected cells.
AB  - ISG15 is an IFN-alpha/beta-induced, ubiquitin-like protein that is conjugated to
      a wide array of cellular proteins through the sequential action of three
      conjugation enzymes that are also induced by IFN-alpha/beta. Recent studies
      showed that ISG15 and/or its conjugates play an important role in protecting
      cells from infection by several viruses, including influenza A virus. However,
      the mechanism by which ISG15 modification exerts antiviral activity has not been
      established. Here we extend the repertoire of ISG15 targets to a viral protein by
      demonstrating that the NS1 protein of influenza A virus (NS1A protein), an
      essential, multifunctional protein, is ISG15 modified in virus-infected cells. We
      demonstrate that the major ISG15 acceptor site in the NS1A protein in infected
      cells is a critical lysine residue (K41) in the N-terminal RNA-binding domain
      (RBD). ISG15 modification of K41 disrupts the association of the NS1A RBD domain
      with importin-alpha, the protein that mediates nuclear import of the NS1A
      protein, whereas the RBD retains its double-stranded RNA-binding activity. Most
      significantly, we show that ISG15 modification of K41 inhibits influenza A virus
      replication and thus contributes to the antiviral action of IFN-beta. We also
      show that the NS1A protein directly and specifically binds to Herc5, the major E3
      ligase for ISG15 conjugation in human cells. These results establish a "loss of
      function" mechanism for the antiviral activity of the IFN-induced ISG15
      conjugation system, namely, that it inhibits viral replication by conjugating
      ISG15 to a specific viral protein, thereby inhibiting its function.

PMID- 20133871
TI  - Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in
      the BNST are differentially affected by stress.
AB  - Long-term depression (LTD) is an important synaptic mechanism for limiting
      excitatory influence over circuits subserving cognitive and emotional behavior. A
      major means of LTD induction is through the recruitment of signaling via G(q)
      linked receptors activated by norepinephrine (NE), acetylcholine, and glutamate.
      Receptors from these transmitter families have been proposed to converge on a
      common postsynaptic LTD maintenance mechanism, such that hetero- and homosynaptic
      induction produce similar alterations in glutamate synapse efficacy. We report
      that in the dorsolateral and ventrolateral bed nucleus of the stria terminalis
      (BNST), recruitment of G(q)-linked receptors by glutamate or NE initiates
      mechanistically distinct forms of postsynaptically maintained LTD and these LTDs
      are differentially regulated by stress exposure. In particular, we show that
      although both mGluR5- and alpha(1)-adrenergic receptor (AR)-dependent LTDs
      involve postsynaptic endocytosis, the alpha(1)-AR-initiated LTD exclusively
      involves modulation of signaling through calcium-permeable AMPA receptors.
      Further, alpha(1)-AR- but not mGluR5- dependent LTD is disrupted by restraint
      stress. alpha(1)-AR LTD is also impaired in mice chronically exposed to ethanol.
      These data thus suggest that in the BNST, NE- and glutamate-activated G(q)-linked
      signaling pathways differentially tune glutamate synapse efficacy in response to
      stress.

PMID- 20133872
TI  - Basic mathematical rules are encoded by primate prefrontal cortex neurons.
AB  - Mathematics is based on highly abstract principles, or rules, of how to
      structure, process, and evaluate numerical information. If and how mathematical
      rules can be represented by single neurons, however, has remained elusive. We
      therefore recorded the activity of individual prefrontal cortex (PFC) neurons in
      rhesus monkeys required to switch flexibly between "greater than" and "less than"
      rules. The monkeys performed this task with different numerical quantities and
      generalized to set sizes that had not been presented previously, indicating that
      they had learned an abstract mathematical principle. The most prevalent activity
      recorded from randomly selected PFC neurons reflected the mathematical rules;
      purely sensory- and memory-related activity was almost absent. These data show
      that single PFC neurons have the capacity to represent flexible operations on
      most abstract numerical quantities. Our findings support PFC network models
      implementing specific "rule-coding" units that control the flow of information
      between segregated input, memory, and output layers. We speculate that these
      neuronal circuits in the monkey lateral PFC could readily have been adopted in
      the course of primate evolution for syntactic processing of numbers in formalized
      mathematical systems.

PMID- 20133870
TI  - Transcriptional patterns in both host and bacterium underlie a daily rhythm of
      anatomical and metabolic change in a beneficial symbiosis.
AB  - Mechanisms for controlling symbiont populations are critical for maintaining the
      associations that exist between a host and its microbial partners. We describe
      here the transcriptional, metabolic, and ultrastructural characteristics of a
      diel rhythm that occurs in the symbiosis between the squid Euprymna scolopes and
      the luminous bacterium Vibrio fischeri. The rhythm is driven by the host's
      expulsion from its light-emitting organ of most of the symbiont population each
      day at dawn. The transcriptomes of both the host epithelium that supports the
      symbionts and the symbiont population itself were characterized and compared at
      four times over this daily cycle. The greatest fluctuation in gene expression of
      both partners occurred as the day began. Most notable was an up-regulation in the
      host of >50 cytoskeleton-related genes just before dawn and their subsequent down
      regulation within 6 h. Examination of the epithelium by TEM revealed a
      corresponding restructuring, characterized by effacement and blebbing of its
      apical surface. After the dawn expulsion, the epithelium reestablished its
      polarity, and the residual symbionts began growing, repopulating the light organ.
      Analysis of the symbiont transcriptome suggested that the bacteria respond to the
      effacement by up-regulating genes associated with anaerobic respiration of
      glycerol; supporting this finding, lipid analysis of the symbionts' membranes
      indicated a direct incorporation of host-derived fatty acids. After 12 h, the
      metabolic signature of the symbiont population shifted to one characteristic of
      chitin fermentation, which continued until the following dawn. Thus, the
      persistent maintenance of the squid-vibrio symbiosis is tied to a dynamic diel
      rhythm that involves both partners.

PMID- 20133873
TI  - Functional reciprocity between Na+ channel Nav1.6 and beta1 subunits in the
      coordinated regulation of excitability and neurite outgrowth.
AB  - Voltage-gated Na(+) channel (VGSC) beta1 subunits regulate cell-cell adhesion and
      channel activity in vitro. We previously showed that beta1 promotes neurite
      outgrowth in cerebellar granule neurons (CGNs) via homophilic cell adhesion, fyn
      kinase, and contactin. Here we demonstrate that beta1-mediated neurite outgrowth
      requires Na(+) current (I(Na)) mediated by Na(v)1.6. In addition, beta1 is
      required for high-frequency action potential firing. Transient I(Na) is unchanged
      in Scn1b (beta1) null CGNs; however, the resurgent I(Na), thought to underlie
      high-frequency firing in Na(v)1.6-expressing cerebellar neurons, is reduced. The
      proportion of axon initial segments (AIS) expressing Na(v)1.6 is reduced in Scn1b
      null cerebellar neurons. In place of Na(v)1.6 at the AIS, we observed an increase
      in Na(v)1.1, whereas Na(v)1.2 was unchanged. This indicates that beta1 is
      required for normal localization of Na(v)1.6 at the AIS during the postnatal
      developmental switch to Na(v)1.6-mediated high-frequency firing. In agreement
      with this, beta1 is normally expressed with alpha subunits at the AIS of P14
      CGNs. We propose reciprocity of function between beta1 and Na(v)1.6 such that
      beta1-mediated neurite outgrowth requires Na(v)1.6-mediated I(Na), and Na(v)1.6
      localization and consequent high-frequency firing require beta1. We conclude that
      VGSC subunits function in macromolecular signaling complexes regulating both
      neuronal excitability and migration during cerebellar development.

PMID- 20133874
TI  - Cocaine effects on mouse incentive-learning and human addiction are linked to
      alpha2 subunit-containing GABAA receptors.
AB  - Because GABA(A) receptors containing alpha2 subunits are highly represented in
      areas of the brain, such as nucleus accumbens (NAcc), frontal cortex, and
      amygdala, regions intimately involved in signaling motivation and reward, we
      hypothesized that manipulations of this receptor subtype would influence
      processing of rewards. Voltage-clamp recordings from NAcc medium spiny neurons of
      mice with alpha2 gene deletion showed reduced synaptic GABA(A) receptor-mediated
      responses. Behaviorally, the deletion abolished cocaine's ability to potentiate
      behaviors conditioned to rewards (conditioned reinforcement), and to support
      behavioral sensitization. In mice with a point mutation in the benzodiazepine
      binding pocket of alpha2-GABA(A) receptors (alpha2H101R), GABAergic
      neurotransmission in medium spiny neurons was identical to that of WT (i.e., the
      mutation was silent), but importantly, receptor function was now facilitated by
      the atypical benzodiazepine Ro 15-4513 (ethyl 8-amido-5,6-dihydro-5-methyl-6-oxo
      4H-imidazo [1,5-a] [1,4] benzodiazepine-3-carboxylate). In alpha2H101R, but not
      WT mice, Ro 15-4513 administered directly into the NAcc-stimulated locomotor
      activity, and when given systemically and repeatedly, induced behavioral
      sensitization. These data indicate that activation of alpha2-GABA(A) receptors
      (most likely in NAcc) is both necessary and sufficient for behavioral
      sensitization. Consistent with a role of these receptors in addiction, we found
      specific markers and haplotypes of the GABRA2 gene to be associated with human
      cocaine addiction.

PMID- 20133875
TI  - Synthetic amyloid-beta oligomers impair long-term memory independently of
      cellular prion protein.
AB  - Inability to form new memories is an early clinical sign of Alzheimer's disease
      (AD). There is ample evidence that the amyloid-beta (Abeta) peptide plays a key
      role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of
      Abeta are proposed as the key mediators of synaptic and cognitive dysfunction,
      but more tractable models of Abeta-mediated cognitive impairment are needed. Here
      we report that, in mice, acute intracerebroventricular injections of synthetic
      Abeta(1-42) oligomers impaired consolidation of the long-term recognition memory,
      whereas mature Abeta(1-42) fibrils and freshly dissolved peptide did not. The
      deficit induced by oligomers was reversible and was prevented by an anti-Abeta
      antibody. It has been suggested that the cellular prion protein (PrP(C)) mediates
      the impairment of synaptic plasticity induced by Abeta. We confirmed that Abeta(1
      42) oligomers interact with PrP(C), with nanomolar affinity. However, PrP
      expressing and PrP knock-out mice were equally susceptible to this impairment.
      These data suggest that Abeta(1-42) oligomers are responsible for cognitive
      impairment in AD and that PrP(C) is not required.

PMID- 20133876
TI  - Hemispheric differences in processing of vocalizations depend on early
      experience.
AB  - An intriguing phenomenon in the neurobiology of language is lateralization: the
      dominant role of one hemisphere in a particular function. Lateralization is not
      exclusive to language because lateral differences are observed in other sensory
      modalities, behaviors, and animal species. Despite much scientific attention, the
      function of lateralization, its possible dependence on experience, and the
      functional implications of such dependence have yet to be clearly determined. We
      have explored the role of early experience in the development of lateralized
      sensory processing in the brain, using the songbird model of vocal learning. By
      controlling exposure to natural vocalizations (through isolation, song tutoring,
      and muting), we manipulated the postnatal auditory environment of developing
      zebra finches, and then assessed effects on hemispheric specialization for
      communication sounds in adulthood. Using bilateral multielectrode recordings from
      a forebrain auditory area known to selectively process species-specific
      vocalizations, we found that auditory responses to species-typical songs and long
      calls, in both male and female birds, were stronger in the right hemisphere than
      in the left, and that right-side responses adapted more rapidly to stimulus
      repetition. We describe specific instances, particularly in males, where these
      lateral differences show an influence of auditory experience with song and/or the
      bird's own voice during development.

PMID- 20133877
TI  - Task2 potassium channels set central respiratory CO2 and O2 sensitivity.
AB  - Task2 K(+) channel expression in the central nervous system is surprisingly
      restricted to a few brainstem nuclei, including the retrotrapezoid (RTN) region.
      All Task2-positive RTN neurons were lost in mice bearing a Phox2b mutation that
      causes the human congenital central hypoventilation syndrome. In plethysmography,
      Task2(-/-) mice showed disturbed chemosensory function with hypersensitivity to
      low CO(2) concentrations, leading to hyperventilation. Task2 probably is needed
      to stabilize the membrane potential of chemoreceptive cells. In addition, Task2(
      /-) mice lost the long-term hypoxia-induced respiratory decrease whereas the
      acute carotid-body-mediated increase was maintained. The lack of anoxia-induced
      respiratory depression in the isolated brainstem-spinal cord preparation
      suggested a central origin of the phenotype. Task2 activation by reactive oxygen
      species generated during hypoxia could silence RTN neurons, thus contributing to
      respiratory depression. These data identify Task2 as a determinant of central
      O(2) chemoreception and demonstrate that this phenomenon is due to the activity
      of a small number of neurons located at the ventral medullary surface.

PMID- 20133878
TI  - A remorin protein interacts with symbiotic receptors and regulates bacterial
      infection.
AB  - Remorin proteins have been hypothesized to play important roles during cellular
      signal transduction processes. Induction of some members of this multigene family
      has been reported during biotic interactions. However, no roles during host
      bacteria interactions have been assigned to remorin proteins until now. We used
      root nodule symbiosis between Medicago truncatula and Sinorhizobium meliloti to
      study the roles of a remorin that is specifically induced during nodulation. Here
      we show that this oligomeric remorin protein attaches to the host plasma membrane
      surrounding the bacteria and controls infection and release of rhizobia into the
      host cytoplasm. It interacts with the core set of symbiotic receptors that are
      essential for perception of bacterial signaling molecules, and thus might
      represent a plant-specific scaffolding protein.

PMID- 20133879
TI  - The type III effector HopF2Pto targets Arabidopsis RIN4 protein to promote
      Pseudomonas syringae virulence.
AB  - Plant immunity can be induced by two major classes of pathogen-associated
      molecules. Pathogen- or microbe-associated molecular patterns (PAMPs or MAMPs)
      are conserved molecular components of microbes that serve as "non-self" features
      to induce PAMP-triggered immunity (PTI). Pathogen effector proteins used to
      promote virulence can also be recognized as "non-self" features or induce a
      "modified-self" state that can induce effector-triggered immunity (ETI). The
      Arabidopsis protein RIN4 plays an important role in both branches of plant
      immunity. Three unrelated type III secretion effector (TTSE) proteins from the
      phytopathogen Pseudomonas syringae, AvrRpm1, AvrRpt2, and AvrB, target RIN4,
      resulting in ETI that effectively restricts pathogen growth. However, no
      pathogenic advantage has been demonstrated for RIN4 manipulation by these TTSEs.
      Here, we show that the TTSE HopF2(Pto) also targets Arabidopsis RIN4. Transgenic
      plants conditionally expressing HopF2(Pto) were compromised for AvrRpt2-induced
      RIN4 modification and associated ETI. HopF2(Pto) interfered with AvrRpt2-induced
      RIN4 modification in vitro but not with AvrRpt2 activation, suggestive of RIN4
      targeting by HopF2(Pto). In support of this hypothesis, HopF2 (Pto) interacted
      with RIN4 in vitro and in vivo. Unlike AvrRpm1, AvrRpt2, and AvrB, HopF2(Pto) did
      not induce ETI and instead promoted P. syringae growth in Arabidopsis. This
      virulence activity was not observed in plants genetically lacking RIN4. These
      data provide evidence that RIN4 is a major virulence target of HopF2(Pto) and
      that a pathogenic advantage can be conveyed by TTSEs that target RIN4.

PMID- 20133880
TI  - PDR-type ABC transporter mediates cellular uptake of the phytohormone abscisic
      acid.
AB  - Abscisic acid (ABA) is a ubiquitous phytohormone involved in many developmental
      processes and stress responses of plants. ABA moves within the plant, and
      intracellular receptors for ABA have been recently identified; however, no ABA
      transporter has been described to date. Here, we report the identification of the
      ATP-binding cassette (ABC) transporter Arabidopsis thaliana Pleiotropic drug
      resistance transporter PDR12 (AtPDR12)/ABCG40 as a plasma membrane ABA uptake
      transporter. Uptake of ABA into yeast and BY2 cells expressing AtABCG40 was
      increased, whereas ABA uptake into protoplasts of atabcg40 plants was decreased
      compared with control cells. In response to exogenous ABA, the up-regulation of
      ABA responsive genes was strongly delayed in atabcg40 plants, indicating that
      ABCG40 is necessary for timely responses to ABA. Stomata of loss-of-function
      atabcg40 mutants closed more slowly in response to ABA, resulting in reduced
      drought tolerance. Our results integrate ABA-dependent signaling and transport
      processes and open another avenue for the engineering of drought-tolerant plants.

PMID- 20133881
TI  - ABC transporter AtABCG25 is involved in abscisic acid transport and responses.
AB  - Abscisic acid (ABA) is one of the most important phytohormones involved in
      abiotic stress responses, seed maturation, germination, and senescence. ABA is
      predominantly produced in vascular tissues and exerts hormonal responses in
      various cells, including guard cells. Although ABA responses require extrusion of
      ABA from ABA-producing cells in an intercellular ABA signaling pathway, the
      transport mechanisms of ABA through the plasma membrane remain unknown. Here we
      isolated an ATP-binding cassette (ABC) transporter gene, AtABCG25, from
      Arabidopsis by genetically screening for ABA sensitivity. AtABCG25 was expressed
      mainly in vascular tissues. The fluorescent protein-fused AtABCG25 was localized
      at the plasma membrane in plant cells. In membrane vesicles derived from AtABCG25
      expressing insect cells, AtABCG25 exhibited ATP-dependent ABA transport. The
      AtABCG25-overexpressing plants showed higher leaf temperatures, implying an
      influence on stomatal regulation. These results strongly suggest that AtABCG25 is
      an exporter of ABA and is involved in the intercellular ABA signaling pathway.
      The presence of the ABA transport mechanism sheds light on the active control of
      multicellular ABA responses to environmental stresses among plant cells.

PMID- 20133883
TI  - Were early Tertiary monotremes really all aquatic? Inferring paleobiology and
      phylogeny from a depauperate fossil record.

PMID- 20133882
TI  - Running enhances spatial pattern separation in mice.
AB  - Increasing evidence suggests that regular exercise improves brain health and
      promotes synaptic plasticity and hippocampal neurogenesis. Exercise improves
      learning, but specific mechanisms of information processing influenced by
      physical activity are unknown. Here, we report that voluntary running enhanced
      the ability of adult (3 months old) male C57BL/6 mice to discriminate between the
      locations of two adjacent identical stimuli. Improved spatial pattern separation
      in adult runners was tightly correlated with increased neurogenesis. In contrast,
      very aged (22 months old) mice had impaired spatial discrimination and low basal
      cell genesis that was refractory to running. These findings suggest that the
      addition of newly born neurons may bolster dentate gyrus-mediated encoding of
      fine spatial distinctions.

PMID- 20133884
TI  - Proposed link between paralytic syndrome and thiamine deficiency in Swedish gulls
      not substantiated.

PMID- 20133885
TI  - First principles-based theory of collective creep.

PMID- 20133886
TI  - Molecular scissors under light control.

PMID- 20133887
TI  - LGP2: positive about viral sensing.

PMID- 20133888
TI  - Excess betaCTF, not Abeta: the culprit in Alzheimer-related endocytic
      dysfunction.

PMID- 20133889
TI  - African great apes are natural hosts of multiple related malaria species,
      including Plasmodium falciparum.
AB  - Plasmodium reichenowi, a chimpanzee parasite, was until very recently the only
      known close relative of Plasmodium falciparum, the most virulent agent of human
      malaria. Recently, Plasmodium gaboni, another closely related chimpanzee
      parasite, was discovered, suggesting that the diversity of Plasmodium circulating
      in great apes in Africa might have been underestimated. It was also recently
      shown that P. reichenowi is a geographically widespread and genetically diverse
      chimpanzee parasite and that the world diversity of P. falciparum is fully
      included within the much broader genetic diversity of P. reichenowi. The evidence
      indicates that all extant populations of P. falciparum originated from P.
      reichenowi, likely by a single transfer from chimpanzees. In this work, we have
      studied the diversity of Plasmodium species infecting chimpanzees and gorillas in
      Central Africa (Cameroon and Gabon) from both wild-living and captive animals.
      The studies in wild apes used noninvasive sampling methods. We confirm the
      presence of P. reichenowi and P. gaboni in wild chimpanzees. Moreover, our
      results reveal the existence of an unexpected genetic diversity of Plasmodium
      lineages circulating in gorillas. We show that gorillas are naturally infected by
      two related lineages of parasites that have not been described previously, herein
      referred to as Plasmodium GorA and P. GorB, but also by P. falciparum, a species
      previously considered as strictly human specific. The continuously increasing
      contacts between humans and primate populations raise concerns about further
      reciprocal host transfers of these pathogens.

PMID- 20133890
TI  - Criteria for scientific evaluation of novel markers: a perspective.

PMID- 20133891
TI  - Perioperative gene expression analysis for prediction of postoperative sepsis.
AB  - BACKGROUND: Postoperative sepsis is one of the main causes of death after major
      abdominal surgery; however, the immunologic factors contributing to the
      development of sepsis are not completely understood. In this study, we evaluated
      gene expression in patients who developed postoperative sepsis and in patients
      with an uncomplicated postoperative course. METHODS: We enrolled 220 patients in
      a retrospective matched-pair, case-control pilot study to investigate the
      perioperative expression of 23 inflammation-related genes regarding their
      properties for predicting postoperative sepsis. Twenty patients exhibiting
      symptoms of sepsis in the first 14 days after surgery (case group) were matched
      with 20 control patients with an uncomplicated postoperative course. Matching
      criteria were sex, age, main diagnosis, type of surgery, and concomitant
      diseases. Blood samples were drawn before surgery and on the first and second
      postoperative days. Relative gene expression was analyzed with real-time reverse
      transcription PCR. RESULTS: Significant differences (P < 0.005) in gene
      expression between the 2 groups were observed for IL1B (interleukin 1, beta), TNF
      [tumor necrosis factor (TNF superfamily, member 2)], CD3D [CD3d molecule, delta
      (CD3-TCR complex)], and PRF1 [perforin 1 (pore forming protein)]. Logistic
      regression analysis and a subsequent ROC curve analysis revealed that the
      combination of TNF, IL1B, and CD3D expression had a specificity and specificity
      of 90% and 85%, respectively, and predicted exclusion of postoperative sepsis
      with an estimated negative predictive value of 98.1%. CONCLUSIONS: These data
      suggest that gene expression analysis may be an effective tool for
      differentiating patients at high and low risk for sepsis after abdominal surgery.

PMID- 20133892
TI  - Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants,
      amitriptyline, imipramine, clomipramine, and trimipramine.
AB  - The role of human UDP glucuronosyltransferase (UGT) 2B10 in the N-glucuronidation
      of a number of tricyclic antidepressants was investigated and compared with that
      of UGT1A4 in both the Sf9 expressed system and human liver microsomes. The
      apparent K(m) (S(50)) values for the formation of quaternary N-glucuronides of
      amitriptyline, imipramine, clomipramine, and trimipramine were 2.60, 16.8, 14.4,
      and 11.2 microM in UGT2B10 and 448, 262, 112, and 258 microM in UGT1A4,
      respectively. The kinetics of amitriptyline and imipramine glucuronidation in
      human liver microsomes exhibited a biphasic character, where the high- and low
      affinity components were in good agreement with our results in expressed UGT2B10
      and UGT1A4, respectively. The kinetics of clomipramine and trimipramine
      glucuronidation in human liver microsomes were sigmoidal in nature, and the S(50)
      values were similar to those found for expressed UGT1A4. The in vitro clearances
      (CL(int) or CL(max)) were comparable between UGT2B10 and UGT1A4 for
      glucuronidation of imipramine, clomipramine, and trimipramine, whereas CL(int) of
      amitriptyline glucuronidation by UGT2B10 was more than 10-fold higher than that
      by UGT1A4. Nicotine was found to selectively inhibit UGT2B10 but not UGT1A4
      activity. At a low tricyclic antidepressant concentration, nicotine inhibited
      their glucuronidation by 33 to 50% in human liver microsomes. Our results suggest
      that human UGT2B10 is a high-affinity enzyme for tricyclic antidepressant
      glucuronidation and is likely to be a major UGT isoform responsible for the
      glucuronidation of these drugs at therapeutic concentrations in vivo.

PMID- 20133893
TI  - Long FLT3 internal tandem duplications and reduced PML-RARalpha expression at
      diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia
      patients.
AB  - BACKGROUND: Internal tandem duplications of the FLT3 gene (FLT3-ITDs) are
      frequent in patients with acute promyelocytic leukemia (APL), however its
      clinical impact remains controversial. DESIGN AND METHODS: We analyzed the
      prognostic significance of FLT3-ITD mutant level and size, as well as FLT3-D835
      point mutations, PML-RARalpha expression and other predictive factors in 129 APL
      patients at diagnosis enrolled on the Spanish LPA96 (n=43) or LPA99 (n=86)
      PETHEMA trials. RESULTS: FLT3-ITDs and D835 mutations were detected in 21% and 9%
      of patients, respectively. Patients with increased ITD mutant/wild-type ratio or
      longer ITD size displayed shorter 5-year relapse-free survival (RFS) (P=0.048 and
      P<0.0001, respectively). However, patients with D835 mutations did not show
      differences in RFS or overall survival (OS). Moreover, patients with initial
      normalized copy number (NCN) of PML-RARalpha transcripts less than the 25(th)
      percentile had adverse clinical features and shorter 5-year RFS (P<0.0001) and OS
      (P=0.004) compared to patients with higher NCN. Patients with low NCN showed
      increased incidence of ITDs (P=0.001), with higher ratios (P<0.0001) and/or
      longer sizes (P=0.007). Multivariate analysis showed that long FLT3-ITD
      (P=0.001), low PML-RARalpha levels (P=0.004) and elevated WBC counts
      (>10x10(9)/L) (P=0.018) were independent predictors for shorter RFS. We
      identified a subgroup of patients with high WBC, long FLT3-ITD and low NCN of
      transcripts that showed an extremely bad prognosis (5-year RFS 23.4%, P<0.0001).
      CONCLUSIONS: In conclusion, FLT3-ITD size and PML-RARalpha transcript levels at
      diagnosis could contribute to improve the risk stratification in APL.

PMID- 20133894
TI  - Long-term immune deficiency after allogeneic stem cell transplantation: B-cell
      deficiency is associated with late infections.
AB  - Immune reconstitution was analyzed in 140 consecutive patients who were 2-year
      disease-free and who underwent myeloablative allogeneic transplantation. A CD4
      and CD8 defect was observed involving naive, terminally differentiated, memory
      and competent cells and above limits values for activated subsets. Natural killer
      cells normalize at six months while we observed expansion of CD19(+)/CD5(+) B
      cells after three months and a persisting defect of memory B cells. Chronic graft
      versus-host disease did not influence significantly those parameters for CD8
      subsets while the naive and competent CD4 subsets were strongly affected. But the
      most profound impact of chronic graft-versus-host disease was on B-cell subsets,
      especially on the memory B population. The cumulative incidence of late severe
      infections was low (14% at four years). Using Cox's models, only low B-cell
      counts at 12 (P=0.02) and 24 (P=0.001) months were associated with the hazard of
      developing late infection, in particular if patients did not develop chronic
      graft-versus-host disease.

PMID- 20133895
TI  - A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal
      antibody) in patients with multiple myeloma.
AB  - This first-in-human, phase I study evaluated the safety, maximum-tolerated dose,
      pharmacokinetics, and antitumor activity of dacetuzumab in 44 patients with
      advanced multiple myeloma. Patients received intravenous dacetuzumab, either in 4
      uniform weekly doses (first 4 cohorts) or using a 5-week intrapatient dose
      escalation schedule (7 subsequent cohorts; the last 3 cohorts received steroid
      pre-medication). An initial dose of 4 mg/kg dacetuzumab exceeded the maximum
      tolerated dose for uniform weekly dosing. Intrapatient dose escalation with
      steroid pre-medication appeared effective in reducing symptoms of cytokine
      release syndrome and the maximum-tolerated dose with this dosing schema was 12
      mg/kg/week. Adverse events potentially related to dacetuzumab included cytokine
      release syndrome symptoms, non-infectious ocular inflammation, and elevated
      hepatic enzymes. Peak dacetuzumab blood levels increased with dose. Nine patients
      (20%) had a best clinical response of stable disease. The observed safety profile
      suggested that dacetuzumab may be combined with other multiple myeloma therapies.
      Two combination trials are ongoing. Clinical trials gov identifier: NCT00079716.

PMID- 20133896
TI  - Increased serum hepcidin and alterations in blood iron parameters associated with
      asymptomatic P. falciparum and P. vivax malaria.
AB  - BACKGROUND: Asymptomatic Plasmodium spp. infections and anemia are highly
      prevalent conditions in tropical regions. We studied whether asymptomatic
      parasitemia induces hepcidin- and/or cytokine-mediated iron maldistribution and
      anemia. DESIGN AND METHODS: A group of 1197 Indonesian schoolchildren, aged 5-15
      years, were screened by microscopy for the presence of parasitemia.
      Concentrations of hemoglobin, serum hepcidin and parameters of iron status and
      inflammation were determined at baseline and 4 weeks after antimalarial
      treatment. RESULTS: Asymptomatic P. falciparum and P. vivax parasitemia were
      detected in 73 (6.1%) and 18 (1.5%) children, respectively, of whom 84% and 83%
      had a C-reactive protein concentration below 5 mg/L. Children with P. falciparum
      or P. vivax parasitemia had significantly lower hemoglobin concentrations than 17
      aparasitemic controls (12.6 and 12.2 g/dL versus 14.4 g/dL; P<0.01), together
      with significantly higher serum hepcidin concentrations (5.2 and 5.6 nM versus
      3.1 nM; P<0.05). The latter was associated with signs of iron maldistribution
      with higher ferritin concentrations and lower values of serum iron concentration,
      transferrin saturation and erythrocyte mean cell volume. Concentrations of growth
      differentiation factor 15 were similar across groups. Antimalarial treatment
      partly reversed these abnormalities and led to a significant increase in
      hemoglobin concentration. CONCLUSIONS: Asymptomatic malarial parasitemia is
      associated with increased hepcidin concentrations and anemia, in the absence of a
      manifest acute phase response. Prolonged iron maldistribution may be an
      underestimated cause of anemia. Screening for parasitemia should be performed
      before starting iron supplementation, as iron therapy may be less effective and
      even hazardous in these circumstances.

PMID- 20133897
TI  - Vorinostat interferes with the signaling transduction pathway of T-cell receptor
      and synergizes with phosphoinositide-3 kinase inhibitors in cutaneous T-cell
      lymphoma.
AB  - BACKGROUND: Vorinostat (suberoylanilide hydroxamic acid, SAHA), an inhibitor of
      class I and II histone deacetylases, has been approved for the treatment of
      cutaneous T-cell lymphoma. In spite of emerging information on the effect of
      vorinostat in many types of cancer, little is yet known about this drug's
      mechanism of action, which is essential for its proper use in combination
      therapy. We investigated alterations in gene expression profile over time in
      cutaneous T-cell lymphoma cells treated with vorinostat. Subsequently, we
      evaluated inhibitors of PI3K, PIM and HSP90 as potential combination agents in
      the treatment of cutaneous T-cell lymphoma. DESIGN AND METHODS: The genes
      significantly up- or down-regulated by vorinostat over different time periods (2
      fold change, false discovery rate corrected P value<0.05) were selected using the
      short-time series expression miner. Cell viability was assessed in vitro in
      cutaneous T-cell lymphoma cells through measuring intracellular ATP content. Drug
      interactions were analyzed by the combination index method with CalcuSyn
      software. RESULTS: The functional analysis suggests that vorinostat modifies
      signaling of T-cell receptor, MAPK, and JAK-STAT pathways. The phosphorylation
      studies of ZAP70 (Tyr319, Tyr493) and its downstream target AKT (Ser473) revealed
      that vorinostat inhibits phosphorylation of these kinases. With regards to
      effects on cutaneous T-cell lymphoma cells, combining vorinostat with PI3K
      inhibitors resulted in synergy while cytotoxic antagonism was observed when
      vorinostat was combined with HSP90 inhibitor. CONCLUSIONS: These results
      demonstrate the potential targets of vorinostat, underlining the importance of T
      cell receptor signaling inhibition following vorinostat treatment. Additionally,
      we showed that combination therapies involving histone deacetylase inhibitors and
      inhibitors of PI3K are potentially efficacious for the treatment of cutaneous T
      cell lymphoma.

PMID- 20133898
TI  - Sex differences in the JAK2 V617F allele burden in chronic myeloproliferative
      disorders.
AB  - BACKGROUND: The JAK2(V617F) allele burden is a variable measure, determined by
      the frequency of mitotic recombination events and the expansion of JAK2(V617F)
      clones. Since variability in the JAK2(V617F) allele burden is partly responsible
      for the distinct phenotypes seen in the myeloproliferative disorders, the
      objective of this study was to identify modifiers of the allele burden. DESIGN
      AND METHODS: Blood samples were obtained between May 2005 and January 2009 from
      272 patients with essential thrombocytosis, polycythemia vera, and myelofibrosis.
      The JAK2(V617F) allele burden was measured by an allele-specific quantitative
      polymerase chain reaction using DNA from purified neutrophils. Repeated measures,
      on average 2 years apart, were available for 104 patients. RESULTS: Sex, age at
      diagnosis, and disease duration all independently influenced the JAK2(V617F)
      allele burden. When considering all patients with myeloproliferative disorders,
      women had significantly lower allele burdens than men (P=0.04). In those patients
      with repeated measures, the increase in allele burden per year between the first
      and second evaluations was significantly less in females than in males. Among
      those who experienced disease evolution, females were 4.5 times more likely to
      have evolution from essential thrombocytosis to polycythemia vera, but 0.23 times
      as likely to have evolution from essential thrombocytosis to myelofibrosis.
      CONCLUSIONS: Sex is an independent factor accounting for variability in the
      JAK2(V617F) allele burden. We speculate that lower allele burdens in females
      reflect a lower frequency of mitotic recombination events in females than in
      males, and should be considered when evaluating the relationship of allele burden
      to disease phenotype and also in evaluating responses to JAK2(V617F)-inhibitors.
      Because sex may influence genotype and/or clonal expansion, underpinning the
      variability in JAK2(V617F) allele burden, it will be important to explore factors
      that determine susceptibility to mitotic recombination events.

PMID- 20133899
TI  - Extracellular K+ is a prerequisite for the function and plasma membrane stability
      of HERG channels.
AB  - RATIONALE: The human ether-a-go-go-related gene (HERG) encodes the pore-forming
      subunits of the rapidly activating delayed rectifier potassium channel (I(Kr))
      that is important for cardiac repolarization. Dysfunction of HERG causes long QT
      syndrome (LQTS) which can lead to sudden cardiac death. We previously showed that
      a reduction in extracellular K(+) concentration ([K(+)](o)) prolongs QT intervals
      in intact rabbits, and decreases the cell surface density of I(Kr) in rabbit
      ventricular myocytes and of the HERG channel expressed in human embryonic kidney
      (HEK) cells. OBJECTIVE: The goal of the present study was to gain insights into
      the mechanisms for low [K(+)](o) induced reduction in HERG expression levels.
      METHODS AND RESULTS: Using patch clamp, Western blot and confocal imaging
      methods, we demonstrated that at low [K(+)](o), the HERG channel entered a novel
      nonconducting state. Furthermore, this novel functional state triggered rapid
      internalization and degradation of the cell surface HERG channels. Thus, our data
      demonstrated for the first time a direct link between a gating state and the
      plasma membrane stability of an ion channel, HERG. Using HERG-permeant cations
      and site-directed mutagenesis, we identified the sites in the channel which are
      involved in the K(+)(o) dependence of HERG channels. CONCLUSIONS: Extracellular
      K(+) is a prerequisite for HERG function and membrane stability.

PMID- 20133900
TI  - Plasminogen activator inhibitor-1 regulates myoendothelial junction formation.
AB  - RATIONALE: Plasminogen activator inhibitor-1 (PAI-1) is a biomarker for several
      vascular disease states; however, its target of action within the vessel wall is
      undefined. OBJECTIVE: Determine the ability of PAI-1 to regulate myoendothelial
      junction (MEJ) formation. METHODS AND RESULTS: MEJs are found throughout the
      vasculature linking endothelial cells (ECs) and vascular smooth muscle cells.
      Using a vascular cell coculture we isolated MEJ fractions and performed two
      dimensional differential gel electrophoresis. Mass spectrometry identified PAI-1
      as being enriched within MEJ fractions, which we confirmed in vivo. In the
      vascular cell coculture, recombinant PAI-1 added to the EC monolayer
      significantly increased MEJs. Conversely, addition of a PAI-1 monoclonal antibody
      to the EC monolayer reduced the number of MEJs. This was also observed in vivo
      where mice fed a high fat diet had increased PAI-1 and MEJs and the number of
      MEJs in coronary arterioles of PAI-1(-/-) mice was significantly reduced when
      compared to C57Bl/6 mice. The presence of MEJs in PAI-1(-/-) coronary arterioles
      was restored when their hearts were transplanted into and exposed to the
      circulation of C57Bl/6 mice. Application of biotin-conjugated PAI-1 to the EC
      monolayer in vitro confirmed the ability of luminal PAI-1 to translocate to the
      MEJ. Functionally, phenylephrine-induced heterocellular calcium communication in
      the vascular cell coculture was temporally enhanced when recombinant PAI-1 was
      present, and prolonged when PAI-1 was absent. CONCLUSION: Our data implicate
      circulating PAI-1 as a key regulator of MEJ formation and a potential target for
      pharmacological intervention in diseases with vascular abnormalities (eg,
      diabetes mellitus).

PMID- 20133901
TI  - Transmural flow modulates cell and fluid transport functions of lymphatic
      endothelium.
AB  - RATIONALE: Lymphatic transport of peripheral interstitial fluid and dendritic
      cells (DCs) is important for both adaptive immunity and maintenance of tolerance
      to self-antigens. Lymphatic drainage can change rapidly and dramatically on
      tissue injury or inflammation, and therefore increased fluid flow may serve as an
      important early cue for inflammation; however, the effects of transmural flow on
      lymphatic function are unknown. OBJECTIVE: Here we tested the hypothesis that
      lymph drainage regulates the fluid and cell transport functions of lymphatic
      endothelium. METHODS AND RESULTS: Using in vitro and in vivo models, we
      demonstrated that lymphatic endothelium is sensitive to low levels of transmural
      flow. Basal-to-luminal flow (0.1 and 1 mum/sec) increased lymphatic permeability,
      dextran transport, and aquaporin-2 expression, as well as DC transmigration into
      lymphatics. The latter was associated with increased lymphatic expression of the
      DC homing chemokine CCL21 and the adhesion molecules intercellular adhesion
      molecule-1 and E-selectin. In addition, transmural flow induced delocalization
      and downregulation of vascular endothelial cadherin and PECAM-1
      (platelet/endothelial cell adhesion molecule-1). Flow-enhanced DC transmigration
      could be reversed by blocking CCR7, intercellular adhesion molecule-1, or E
      selectin. In an experimental model of lymphedema, where lymphatic drainage is
      greatly reduced or absent, lymphatic endothelial expression of CCL21 was nearly
      absent. CONCLUSIONS: These findings introduce transmural flow as an important
      regulator of lymphatic endothelial function and suggest that flow might serve as
      an early inflammatory signal for lymphatics, causing them to regulate transport
      functions to facilitate the delivery of soluble antigens and DCs to lymph nodes.

PMID- 20133902
TI  - Aortic arch curvature and atherosclerosis have overlapping quantitative trait
      loci in a cross between 129S6/SvEvTac and C57BL/6J apolipoprotein E-null mice.
AB  - RATIONALE: Apolipoprotein E-null mice with a 129S6/SvEvTac strain background (129
      apoE) develop atherosclerotic plaques faster in the aortic arch but slower in the
      aortic root than those with a C57BL/6J background (B6-apoE). The shape of the
      aortic arch also differs in the 2 strains. OBJECTIVE: Because circulating plasma
      factors are the same at both locations, we tested the hypothesis that genetic
      factors affecting vascular geometry also affect the location and extent of
      atherosclerotic plaque development. METHODS AND RESULTS: Tests on the F2 progeny
      from a cross between 129-apoE-null and B6-apoE-null mice showed that the extent
      of atherosclerosis in the aortic arch is significantly correlated in males, but
      not in females, with the shape of arch curvature (r=0.34, P<0.0001) and weakly
      with the arch diameter (r=0.20, P=0.02). Quantitative trait locus (QTL) analysis
      identified 2 significant peaks for aortic arch lesion size on chromosome 1 (105
      Mb, LOD=5.0, and 163 Mb, LOD=6.8), and a suggestive QTL on chromosome 15 (96 Mb,
      LOD=4.7). A significant QTL for aortic root lesion size was on chromosome 9 (61
      Mb, LOD=6.9), but it was distinct from the QTLs for arch lesion size. Remarkably,
      the QTLs for susceptibility to atherosclerosis in the arch overlapped with a
      significant QTL that affects curvature of the arch on chromosome 1 (121 Mb,
      LOD=5.6) and a suggestive QTL on chromosome 15 (76 Mb, LOD=3.5). CONCLUSIONS: The
      overlapping QTLs for curvature of the aortic arch and atherosclerosis support
      that the ontogeny of the aortic arch formation is a potential risk factor for
      atherosclerosis.

PMID- 20133904
TI  - The year's successes in failure: Circulation Research takes a look at the key
      research developments of 2009 that are providing hope in the field of heart
      failure.

PMID- 20133903
TI  - Activation of the ROCK1 branch of the transforming growth factor-beta pathway
      contributes to RAGE-dependent acceleration of atherosclerosis in diabetic ApoE
      null mice.
AB  - RATIONALE: The multiligand RAGE (receptor for advanced glycation end products)
      contributes to atherosclerosis in apolipoprotein (Apo)E-null mice. OBJECTIVE: To
      delineate the specific mechanisms by which RAGE accelerated atherosclerosis, we
      performed Affymetrix gene expression arrays on aortas of nondiabetic and diabetic
      ApoE-null mice expressing RAGE or devoid of RAGE at nine weeks of age, as this
      reflected a time point at which frank atherosclerotic lesions were not yet
      present, but that we would be able to identify the genes likely involved in
      diabetes- and RAGE-dependent atherogenesis. METHODS AND RESULTS: We report that
      there is very little overlap of the genes that are differentially expressed both
      in the onset of diabetes in ApoE-null mice, and in the effect of RAGE deletion in
      diabetic ApoE-null mice. Pathway-Express analysis revealed that the transforming
      growth factor-beta pathway and focal adhesion pathways might be expected to play
      a significant role in both the mechanism by which diabetes facilitates the
      formation of atherosclerotic plaques in ApoE-null mice, and the mechanism by
      which deletion of RAGE ameliorates this effect. Quantitative polymerase chain
      reaction studies, Western blotting, and confocal microscopy in aortic tissue and
      in primary cultures of murine aortic smooth muscle cells supported these
      findings. CONCLUSIONS: Taken together, our work suggests that RAGE-dependent
      acceleration of atherosclerosis in ApoE-null mice is dependent, at least in part,
      on the action of the ROCK1 (rho-associated protein kinase 1) branch of the
      transforming growth factor-beta pathway.

PMID- 20133905
TI  - The new circulation research: a manifesto.

PMID- 20133906
TI  - Vascular dendritic cells as gatekeepers of lipid accumulation within nascent
      atherosclerotic plaques.

PMID- 20133907
TI  - Targeting sarcoplasmic reticulum Ca2+ uptake to improve heart failure: hit or
      miss.

PMID- 20133908
TI  - Another broken heart: loss of lamina-associated polypeptide 2alpha causes
      systolic dysfunction.

PMID- 20133909
TI  - Be still, my beating heart: never!

PMID- 20133910
TI  - Development of the pacemaker tissues of the heart.
AB  - Pacemaker and conduction system myocytes play crucial roles in initiating and
      regulating the contraction of the cardiac chambers. Genetic defects, acquired
      diseases, and aging cause dysfunction of the pacemaker and conduction tissues,
      emphasizing the clinical necessity to understand the molecular and cellular
      mechanisms of their development and homeostasis. Although all cardiac myocytes of
      the developing heart initially possess pacemaker properties, the majority
      differentiates into working myocardium. Only small populations of embryonic
      myocytes will form the sinus node and the atrioventricular node and bundle.
      Recent efforts have revealed that the development of these nodal regions is
      achieved by highly localized suppression of working muscle differentiation, and
      have identified transcriptional repressors that mediate this process. This review
      will summarize and reflect new experimental findings on the cellular origin and
      the molecular control of differentiation and morphogenesis of the pacemaker
      tissues of the heart. It will also shed light on the etiology of inborn and
      acquired errors of nodal tissues.

PMID- 20133911
TI  - Mapping cardiac pacemaker circuits: methodological puzzles of the sinoatrial node
      optical mapping.
AB  - Historically, milestones in science are usually associated with methodological
      breakthroughs. Likewise, the advent of electrocardiography, microelectrode
      recordings and more recently optical mapping have ushered in new periods of
      significance of advancement in elucidating basic mechanisms in cardiac
      electrophysiology. As with any novel technique, however, data interpretation is
      challenging and should be approached with caution, as it cannot be simply
      extrapolated from previously used methodologies and with experience and time
      eventually becomes validated. A good example of this is the use of optical
      mapping in the sinoatrial node (SAN): when microelectrode and optical recordings
      are obtained from the same site in myocardium, significantly different results
      may be noted with respect to signal morphology and as a result have to be
      interpreted by a different set of principles. Given the rapid spread of the use
      of optical mapping, careful evaluation must be made in terms of methodology with
      respect to interpretation of data gathered by optical sensors from fluorescent
      potential-sensitive dyes. Different interpretations of experimental data may lead
      to different mechanistic conclusions. This review attempts to address the origin
      and interpretation of the "double component" morphology in the optical action
      potentials obtained from the SAN region. One view is that these 2 components
      represent distinctive signals from the SAN and atrial cells and can be fully
      separated with signal processing. A second view is that the first component
      preceding the phase 0 activation represents the membrane currents and
      intracellular calcium transients induced diastolic depolarization from the SAN.
      Although the consensus from both groups is that ionic mechanisms, namely the
      joint action of the membrane and calcium automaticity, are important in the SAN
      function, it is unresolved whether the double-component originates from the
      recording methodology or represents the underlying physiology. This overview aims
      to advance a common understanding of the basic principles of optical mapping in
      complex 3D anatomic structures.

PMID- 20133912
TI  - Protein acetylation in the cardiorenal axis: the promise of histone deacetylase
      inhibitors.
AB  - Acetylation of histone and nonhistone proteins provides a key mechanism for
      controlling signaling and gene expression in heart and kidney. Pharmacological
      inhibition of protein deacetylation with histone deacetylase (HDAC) inhibitors
      has shown promise in preclinical models of cardiovascular and renal disease.
      Efficacy of HDAC inhibitors appears to be governed by pleiotropic salutary
      actions on a variety of cell types and pathophysiological processes, including
      myocyte hypertrophy, fibrosis, inflammation and epithelial-to-mesenchymal
      transition, and occurs at compound concentrations below the threshold required to
      elicit toxic side effects. We review the roles of acetylation/deacetylation in
      the heart and kidney and provide rationale for extending HDAC inhibitors into
      clinical testing for indications involving these organs.

PMID- 20133914
TI  - Back to the ground.

PMID- 20133913
TI  - Protein S-nitrosylation and cardioprotection.
AB  - Nitric oxide (NO) plays an important role in the regulation of cardiovascular
      function. In addition to the classic NO activation of the cGMP-dependent pathway,
      NO can also regulate cell function through protein S-nitrosylation, a redox
      dependent, thiol-based, reversible posttranslational protein modification that
      involves attachment of an NO moiety to a nucleophilic protein sulfhydryl group.
      There are emerging data suggesting that S-nitrosylation of proteins plays an
      important role in cardioprotection. Protein S-nitrosylation not only leads to
      changes in protein structure and function but also prevents these thiol(s) from
      further irreversible oxidative/nitrosative modification. A better understanding
      of the mechanism regulating protein S-nitrosylation and its role in
      cardioprotection will provide us new therapeutic opportunities and targets for
      interventions in cardiovascular diseases.

PMID- 20133915
TI  - A risk score to predict future atrial fibrillation derived from patients with
      stroke initially presenting with atrial fibrillation?

PMID- 20133916
TI  - High doses of statins and stroke outcome.

PMID- 20133917
TI  - Years of disability-adjusted life gained as a result of thrombolytic therapy for
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Disability-adjusted life year (DALY) metric reflects
      years of healthy life lost because of living with disability and years of life
      lost because of premature mortality. Widely used in epidemiological analyses,
      DALY has not been applied to acute stroke trials. METHODS: From previous studies,
      we derived, for each modified Rankin Scale level, disability weights, disability
      linked mortality hazard ratios, and age-specific life expectancies. We then
      analyzed patient level data from the 2 publicly available National Institute of
      Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen
      activator trials. For each subject, we abstracted age, treatment assignment, and
      3-month modified Rankin Scale outcome and calculated the DALYs lost resulting
      from the qualifying stroke. RESULTS: The disability-linked hazard ratios for
      premature annual mortality for a modified Rankin Scale score of 0 to 5 were 1.53,
      1.52, 2.17, 3.18, 4.55, and 6.55, respectively. In the NINDS recombinant tissue
      plasminogen activator trials, DALYs (mean+/-SE) lost as a result of the
      qualifying stroke were substantially less with recombinant tissue plasminogen
      activator than with placebo (4.64+/-0.17 versus 5.91+/-0.21; P<0.0001), a finding
      that remained robust after adjustment for baseline prognostic factors. When DALYs
      gained were apportioned to the 29% of patients experiencing any benefit from
      lytic therapy, each patient gained an average of 4.4 DALYs. DALY analysis showed
      greater power than dichotomized modified Rankin Scale analysis in discriminating
      treatment effects overall and in patients >or=70 years of age. CONCLUSIONS: For
      patients who benefit from treatment, <3-hour thrombolytic therapy adds the
      equivalent of 4.4 years of healthy life, free of disability. The DALY metric
      provides a continuous scale that increases statistical power, is intuitively
      understandable, and is applicable to a wide range of conditions and treatments.

PMID- 20133918
TI  - Pattern of response of National Institutes of Health Stroke Scale components to
      early recanalization in the CLOTBUST trial.
AB  - BACKGROUND AND PURPOSE: Early recanalization is the likely mechanism by which
      intravenous thrombolysis improves stroke outcomes. Limited data exist on the
      patterns of early recovery of various brain functions. METHODS: Data from the
      Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and
      Systemic t-PA (CLOTBUST) trial was used to determine time-related trends in
      neurological function recovery, as measured by National Institutes of Health
      Stroke Scale (NIHSS) components at baseline, 30, 60, 90, 120 minutes, and 24
      hours. Repeated-measures ANOVA was used to compare patients with complete
      recanalization versus no or partial recanalization of the middle cerebral artery
      (MCA) at 120 minutes from tissue plasminogen activator bolus. The correlation
      structure of the NIHSS was analyzed with multivariable factor analysis. The
      ability of individual components to diagnose recanalization was assessed with
      area under the receiver operating characteristic curves. RESULTS: Altogether, 113
      patients from the CLOTBUST trial had complete follow-up NIHSS scores available.
      All received 0.9 mg/kg IV tissue plasminogen activator within 3 hours of symptom
      onset (mean age 69+/-12 years; 58% men; median NIHSS 16; complete MCA
      recanalization 27%). All NIHSS components attributable to MCA occlusion
      contributed with varying degrees to the decrease of the total NIHSS score after
      MCA recanalization. NIHSS components responded in 2 major and mutually
      independent clusters representing left and right brain functions. The best
      performing component in diagnosing recanalization was gaze deviation (area under
      the receiver operating characteristic curve=0.80), but its results were similar
      to the total NIHSS score (area under the receiver operating characteristic
      curve=0.75). CONCLUSIONS: All neurological functions, impaired because of MCA
      occlusion, recovered after recanalization, although not to the same extent. The
      total NIHSS score is more useful than the individual components in detecting MCA
      recanalization.

PMID- 20133919
TI  - Hyperlipidemia and reduced white matter hyperintensity volume in patients with
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensity (WMH), or leukoaraiosis, is a
      radiologic finding generally assumed to reflect diseased small cerebral
      vasculature. WMH has significant functional impact through its relation to
      cognitive decline and risk of ischemic and hemorrhagic stroke. Accumulating
      evidence suggests that some manifestations of small-vessel disease such as
      intracerebral hemorrhage are associated with low levels of cholesterol. We sought
      to determine the relation between hyperlipidemia and WMH severity in patients
      with acute ischemic stroke (AIS). METHODS: We analyzed 2 independent, hospital
      based AIS cohorts. Demographic and clinical data were collected prospectively.
      WMH was measured using semiautomated volumetric image analysis and a
      semiquantitative visual grading scale. Univariate and multivariable regression
      analyses were used to assess the relation between WMH severity and study
      variables. RESULTS: A total of 631 and 504 subjects in the first and second
      cohorts, respectively, were included. In univariate analyses, advancing age and
      hypertension were associated with severity of WMH (P<0.001) in both cohorts. In
      the multivariable analysis, after controlling for age, sex, and significant risk
      factors in the univariate and age-adjusted analyses, patients with a history of
      hyperlipidemia had less severe WMH in both cohorts (P<0.01). CONCLUSIONS: Results
      from 2 independent cohorts demonstrate that AIS patients with a history of
      hyperlipidemia have less severe WMH at the time of stroke. These data support the
      hypothesis that hyperlipidemia may play a relatively protective role in cerebral
      small-vessel disease.

PMID- 20133920
TI  - Women's reporting of sexual and physical assaults to police in the National
      Violence Against Women Survey.
AB  - Previous research has assumed that rape reporting is unique, but no study has
      systematically tested this assumption. The present study used a probability
      sample of female victims from the National Violence Against Women Survey to
      compare factors affecting rape and physical assault reporting using multinomial
      logit regression. Overall, results suggested that there was similarity in
      reporting decisions between rapes and physical assaults in terms of main effects.
      However, interactions suggested that age, marital status, and physical force each
      influenced reporting differently by assault type. Implications of these results
      are discussed and directions for future research are offered.

PMID- 20133921
TI  - "Fathers' rights" and the defense of paternal authority in Australia.
AB  - Feminism's achievements regarding violence against women are a key target for the
      fathers' rights movement. This article provides an overview of the impact of the
      fathers' rights movement on men's violence against women. It documents the ways
      in which fathers' rights groups in Australia have influenced changes in family
      law, which privilege parental contact over safety, particularly through moves
      toward a presumption of children's joint residence. They have attempted to
      discredit female victims of violence, to wind back the legal protections
      available to victims and the sanctions imposed on perpetrators, and to undermine
      services for the victims of men's violence.

PMID- 20133922
TI  - Losing the "gender" in gender-based violence: the missteps of research on dating
      and intimate partner violence.

PMID- 20133923
TI  - What genes tell us about the pathogenesis of asthma and chronic obstructive
      pulmonary disease.
AB  - Recently a series of genome-wide association study manuscripts in asthma and
      chronic obstructive pulmonary disease have been published. These papers suggest
      that, in part, asthma and chronic obstructive pulmonary disease have a common
      genetic origin, and that this common origin is due to polymorphism in genes that
      are involved with the development of the lung. This Pulmonary Perspective
      discusses what we are learning from genome-wide association studies, where the
      field of genetics and genomics is headed, and how this knowledge will ultimately
      be put to use in clinical medicine.

PMID- 20133924
TI  - Surfactant protein-d inhibits lung inflammation caused by ventilation in
      premature newborn lambs.
AB  - RATIONALE: Premature newborns frequently require manual ventilation for
      resuscitation during which lung injury occurs. Although surfactant protein (SP)-D
      regulates pulmonary inflammation, SP-D levels are low in the preterm lung.
      Commercial surfactants for treatment of respiratory distress syndrome do not
      contain SP-D. OBJECTIVES: To determine whether addition of recombinant human SP-D
      (rhSP-D) to commercial surfactant influences lung inflammation in ventilated
      premature newborn lambs. METHODS: Prematurely delivered lambs (130 d gestation
      age) were resuscitated with 100% O(2) and peak inspiratory pressure 40 cm H(2)O
      for 20 minutes and then treated with Survanta or Survanta containing rhSP-D.
      Ventilation was then changed to regulate tidal volume at 8 to 9 ml/kg. At 5 hours
      of age lambs were killed for sample collection. MEASUREMENTS AND MAIN RESULTS:
      Sequential blood gas and tidal volume were similar in lambs treated with or
      without rhSP-D, indicating that lung immaturity and ventilatory stress used to
      support premature lambs were comparable between the two groups. Ventilation
      caused pulmonary inflammation in lambs treated with surfactant alone. In
      contrast, surfactant containing rhSP-D decreased neutrophil numbers in
      bronchoalveolar lavage fluid and decreased neutrophil elastase activity in lung
      tissue. IL-8 mRNA and IL-8 protein were significantly decreased in the +rhSP-D
      group lamb lungs, to 20% of those in controls. The addition of rhSP-D also
      rendered Survanta more resistant to plasma protein inhibition of surfactant
      function. CONCLUSIONS: Treatment with rhSP-D-containing surfactant inhibited lung
      inflammation and enhanced the resistance of surfactant to inhibition, supporting
      its potential usefulness for prevention of lung injury in the preterm newborn.

PMID- 20133925
TI  - Critical comparisons of the clinical performance of oxygen-conserving devices.
AB  - RATIONALE: Clinical testing of oxygen-conserving devices is not mandated before
      marketing. Consequently, little is known about individual or comparative
      therapeutic effectiveness. OBJECTIVES: To relate oxygen delivery from
      prototypical instruments to physiological performance. METHODS: Thirteen subjects
      with obstructive lung disease performed progressive treadmill exercise while
      inhaling either room air, 2 L O(2)/min, or bolus oxygen from four commercially
      available conserving devices at regulator settings of 2, 5, and continuous. The
      devices were studied blindly in random order after first being tested to
      determine performance characteristics. Pulse oximetry, oxygen delivery, and nasal
      and oral ventilations were monitored at rest and with exertion. MEASUREMENTS AND
      MAIN RESULTS: At a setting of 2 at rest, all conservers maintained saturation
      greater than 90%, but there were significant differences in oxygenation between
      systems. Only one equaled 2 L O(2)/min. With exertion, saturation decreased with
      all conservers but not with 2 L O(2)/min. One device did not perform any better
      than room air. Two systems provided less oxygen than predicted, one more, and in
      one the expected and actual amounts were equal only at rest. Breath-by-breath
      performance was highly variable, with irregular activation and inconsistent
      oxygen bolus size delivery. Increasing oxygen pulse volume to the point of
      eradicating conservation with the continuous setting did not eliminate all
      disparities. CONCLUSIONS: The mechanical and clinical performances of current
      oxygen conservers are highly variable and in some instances actually contribute
      to limitations in exercise ability. Seemingly equivalent technical features do
      not guarantee equivalent therapeutic functionality.

PMID- 20133926
TI  - Chronic cigarette smoke exposure generates pathogenic T cells capable of driving
      COPD-like disease in Rag2-/- mice.
AB  - RATIONALE: Pathogenic T cells drive, or sustain, a number of inflammatory
      diseases. Chronic obstructive pulmonary disease (COPD) is an inflammatory lung
      disease associated with the accumulation of activated T cells. We previously
      demonstrated that chronic cigarette smoke (CS) exposure causes oligoclonal
      expansion of lung CD4(+) T cells and CD8(+) T cells in a mouse model of COPD,
      thus implicating these cells in disease pathogenesis. OBJECTIVES: To determine
      whether T cells are pathogenic in a CS-induced mouse model of COPD. METHODS: We
      transferred lung CD3(+) T cells from filtered air (FA)- and CS-exposed mice into
      Rag2(-/-) recipients. Endpoints associated with the COPD phenotype were then
      measured. MEASUREMENTS AND MAIN RESULTS: Here, we demonstrate that chronic CS
      exposure generates pathogenic T cells. Transfer of CD3(+) T cells from the lungs
      of CS-exposed mice into Rag2(-/-) recipients led to substantial pulmonary changes
      pathognomonic of COPD. These changes included monocyte/macrophage and neutrophil
      accumulation, increased expression of cytokines and chemokines, activation of
      proteases, apoptosis of alveolar epithelial cells, matrix degradation, and
      airspace enlargement reminiscent of emphysema. CONCLUSIONS: These data formally
      demonstrate, for the first time, that chronic CS exposure leads to the generation
      of pathogenic T cells capable of inducing COPD-like disease in Rag2(-/-) mice.
      This report provides novel insights into COPD pathogenesis.

PMID- 20133927
TI  - Resistance training prevents deterioration in quadriceps muscle function during
      acute exacerbations of chronic obstructive pulmonary disease.
AB  - RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) acutely
      reduce skeletal muscle strength and result in long-term loss of functional
      capacity. OBJECTIVES: To investigate whether resistance training is feasible and
      safe and can prevent deteriorating muscle function during exacerbations of COPD.
      METHODS: Forty patients (FEV(1) 49 +/- 17% predicted) hospitalized with a severe
      COPD exacerbation were randomized to receive usual care or an additional
      resistance training program during the hospital admission. Patients were followed
      up for 1 month after discharge. Primary outcomes were quadriceps force and
      systemic inflammation. A muscle biopsy was taken in a subgroup of patients to
      assess anabolic and catabolic pathways. MEASUREMENTS AND MAIN RESULTS: Resistance
      training did not yield higher systemic inflammation as indicated by C-reactive
      protein levels and could be completed uneventfully. Enhanced quadriceps force was
      seen at discharge (+9.7 +/- 16% in the training group; -1 +/- 13% in control
      subjects; P = 0.05) and at 1 month follow-up in the patients who trained. The 6
      minute walking distance improved after discharge only in the group who received
      resistance training (median 34; interquartile range, 14-61 m; P = 0.002). In a
      subgroup of patients a muscle biopsy showed a more anabolic status of skeletal
      muscle in patients who followed training. Myostatin was lower (P = 0.03) and the
      myogenin/MyoD ratio tended to be higher (P = 0.08) in the training group compared
      with control subjects. CONCLUSIONS: Resistance training is safe, successfully
      counteracts skeletal muscle dysfunction during acute exacerbations of COPD, and
      may up-regulate the anabolic milieu in the skeletal muscle. Clinical trial
      registered with www.clinicaltrials.gov (NCT00877084).

PMID- 20133928
TI  - Growth of lung parenchyma in infants and toddlers with chronic lung disease of
      infancy.
AB  - RATIONALE: The clinical pathology describing infants with chronic lung disease of
      infancy (CLDI) has been limited and obtained primarily from infants with severe
      lung disease, who either died or required lung biopsy. As lung tissue from
      clinically stable outpatients is not available, physiological measurements offer
      the potential to increase our understanding of the pulmonary pathophysiology of
      this disease. OBJECTIVES: We hypothesized that if premature birth and the
      development of CLDI result in disruption of alveolar development, then infants
      and toddlers with CLDI would have a lower pulmonary diffusing capacity relative
      to their alveolar volume compared with full-term control subjects. METHODS: We
      measured pulmonary diffusing capacity and alveolar volume, using a single breath
      hold maneuver at elevated lung volume. Subjects with chronic lung disease of
      infancy (23-29 wk of gestation; n = 39) were compared with full-term control
      subjects (n = 61) at corrected ages of 11.6 (4.8-17.0) and 13.6 (3.2-33) months,
      respectively. MEASUREMENTS AND MAIN RESULTS: Alveolar volume and pulmonary
      diffusing capacity increased with increasing body length for both groups. After
      adjusting for body length, subjects with CLDI had significantly lower pulmonary
      diffusing capacity (2.88 vs. 3.23 ml/min/mm Hg; P = 0.0004), but no difference in
      volume (545 vs. 555 ml; P = 0.58). CONCLUSIONS: Infants and toddlers with CLDI
      have decreased pulmonary diffusing capacity, but normal alveolar volume. These
      physiological findings are consistent with the morphometric data obtained from
      subjects with severe lung disease, which suggests an impairment of alveolar
      development after very premature birth.

PMID- 20133929
TI  - Efficacy of corticosteroids in community-acquired pneumonia: a randomized double
      blinded clinical trial.
AB  - RATIONALE: Some studies have shown a beneficial effect of corticosteroids in
      patients with community-acquired pneumonia (CAP), possibly by diminishing local
      and systemic antiinflammatory host response. OBJECTIVES: To assess the efficacy
      of adjunctive prednisolone treatment in patients hospitalized with CAP. METHODS:
      Hospitalized patients, clinically and radiologically diagnosed with CAP using
      standard clinical and radiological criteria, were randomized to receive 40 mg
      prednisolone for 7 days or placebo, along with antibiotics. Primary outcome was
      clinical cure at Day 7. Secondary outcomes were clinical cure at Day 30, length
      of stay, time to clinical stability, defervescence, and C-reactive protein.
      Disease severity was scored using CURB-65 (a severity index for community
      acquired pneumonia evaluating Confusion, blood Urea nitrogen, Respiratory rate,
      Blood pressure, and age 65 or older) and Pneumonia Severity Index. MEASUREMENTS
      AND MAIN RESULTS: We enrolled 213 patients. Fifty-four (25.4%) patients had a
      CURB-65 score greater than 2, and 93 (43.7%) patients were in Pneumonia Severity
      Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 (80.8%) and 69/104
      (66.3%) in the prednisolone group and 93/109 (85.3%) and 84/109 (77.1%) in the
      placebo group (P = 0.38 and P = 0.08). Patients on prednisolone had faster
      defervescence and faster decline in serum C-reactive protein levels compared with
      placebo. Subanalysis of patients with severe pneumonia did not show differences
      in clinical outcome. Late failure (>72 h after admittance) was more common in the
      prednisolone group (20 patients, 19.2%) than in the placebo group (10 patients,
      6.4%; P = 0.04). Adverse events were few and not different between the two
      groups. CONCLUSIONS: Prednisolone (at 40 mg) once daily for a week does not
      improve outcome in hospitalized patients with CAP. A benefit in more severely ill
      patients cannot be excluded. Because of its association with increased late
      failure and lack of efficacy prednisolone should not be recommended as routine
      adjunctive treatment in CAP.

PMID- 20133931
TI  - Expression of high-mobility group box 1 and of receptor for advanced glycation
      end products in chronic obstructive pulmonary disease.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by
      airway inflammation and remodeling. High-mobility group box 1 (HMGB1), a nuclear
      protein that is released during inflammation and repair, interacts with
      proinflammatory cytokines and with the receptor for advanced glycation end
      products (RAGE), which is highly expressed in the lung. OBJECTIVES: To determine
      whether HMGB1 is augmented in COPD and is associated with IL-1beta and RAGE.
      METHODS: HMGB1 was assessed in the bronchoalveolar lavage (BAL) of 20 never
      smokers, 20 smokers, and 30 smokers with COPD and it was correlated with
      inflammatory and clinical parameters. In parallel, HMGB1 and RAGE
      immunolocalization was determined in bronchial and lung tissues. Last, binding of
      HMGB1 to IL-1beta in human macrophages and in BAL fluid was examined.
      MEASUREMENTS AND MAIN RESULTS: BAL levels of HMGB1 were higher in smokers with
      COPD than in smokers and never-smokers (P < 0.0001 for both comparisons), and
      similar differences were observed in epithelial cells and alveolar macrophages.
      BAL HMGB1 correlated positively with IL-1beta (r(s) = 0.438; P = 0.0006) and
      negatively with FEV(1) (r(s) = -0.570; P < 0.0001) and transfer factor of the
      lung for carbon monoxide (r(s) = -0.382; P = 0.0026). HMGB1-IL-1beta complexes
      were found in BAL supernatant and alveolar macrophages from smokers and patients
      with COPD, as well as in the human macrophage cell line, THP-1, where they
      enhanced the synthesis of tumor-necrosis factor-alpha. RAGE was overexpressed in
      the airway epithelium and smooth muscle of patients with COPD and it colocalized
      with HMGB1. CONCLUSIONS: Elevated HMGB1 expression in COPD airways may sustain
      inflammation and remodeling through its interaction with IL-1beta and RAGE.

PMID- 20133930
TI  - Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype
      among patients with asthma.
AB  - RATIONALE: Exhaled nitric oxide (Fe(NO)) is a biomarker of airway inflammation in
      mild to moderate asthma. However, whether Fe(NO) levels are informative regarding
      airway inflammation in patients with severe asthma, who are refractory to
      conventional treatment, is unknown. Here, we hypothesized that classification of
      severe asthma based on airway inflammation as defined by Fe(NO) levels would
      identify a more reactive, at-risk asthma phenotype. METHODS: Fe(NO) and major
      features of asthma, including airway inflammation, airflow limitation,
      hyperinflation, hyperresponsiveness, and atopy, were determined in 446
      individuals with various degrees of asthma severity (175 severe, 271 non-severe)
      and 49 healthy subjects enrolled in the Severe Asthma Research Program.
      MEASUREMENTS AND MAIN RESULTS: Fe(NO) levels were similar among patients with
      severe and non-severe asthma. The proportion of individuals with high Fe(NO)
      levels (>35 ppb) was the same (40%) among groups despite greater corticosteroid
      therapy in severe asthma. All patients with asthma and high Fe(NO) had more
      airway reactivity (maximal reversal in response to bronchodilator administration
      and by methacholine challenge), more evidence of allergic airway inflammation
      (sputum eosinophils), more evidence of atopy (positive skin tests, higher serum
      IgE and blood eosinophils), and more hyperinflation, but decreased awareness of
      their symptoms. High Fe(NO) identified those patients with severe asthma
      characterized by the greatest airflow obstruction and hyperinflation and most
      frequent use of emergency care. CONCLUSIONS: Grouping of asthma by Fe(NO)
      provides an independent classification of asthma severity, and among patients
      with severe asthma identifies the most reactive and worrisome asthma phenotype.

PMID- 20133932
TI  - Direct transthoracic access to the left ventricle for catheter ablation of
      ventricular tachycardia.
AB  - BACKGROUND: Percutaneous approaches for radiofrequency ablation of ventricular
      tachycardia (VT) in the left ventricle are typically transarterial retro-aortic,
      antegrade transmitral via an interatrial septal puncture, or epicardial. However,
      all 3 approaches may be contraindicated in certain cases. We describe 2 cases of
      VT ablation in which aortic and mitral valve replacements did not permit
      utilization of any of these techniques. METHODS AND RESULTS: Direct access to the
      left ventricular cavity was achieved with a percutaneous puncture through the
      intercostal space overlying the apex in the first case and through a left
      minithoracotomy in the second. A sheath was then inserted via the Seldinger
      technique, allowing catheter access for mapping and ablation of the VT. After
      successful ablation, the sheaths were withdrawn and hemostasis was achieved. A
      large left hemothorax occurred from the left ventricular apical puncture in the
      first case. Direct closure with a purse-string suture in the second case achieved
      hemostasis. CONCLUSIONS: Direct percutaneous left ventricular puncture is a
      viable option for mapping and ablation of left ventricular VT. A minithoracotomy
      allows better hemostatic control. This technique has a role when other
      percutaneous approaches are contraindicated.

PMID- 20133933
TI  - Characterization, mapping, and catheter ablation of recurrent atrial tachycardias
      after stepwise ablation of long-lasting persistent atrial fibrillation.
AB  - BACKGROUND: Atrial tachycardias (AT) often occur after ablation of long-lasting
      persistent AF (CAF) and are difficult to treat conservatively. This study
      evaluated mechanisms and success rates of conventional mapping and catheter
      ablation of recurrent ATs occurring late after stepwise ablation of CAF. METHODS
      AND RESULTS: A total of 320 patients underwent de novo ablation of CAF using a
      stepwise ablation approach in 2006 to 2007 at our institution. This study
      comprised patients who presented with recurrent ATs at their first redo procedure
      after initial de novo CAF ablation. All procedures were guided by conventional
      mapping techniques exclusively. Sixty-one patients (63+/-10 years, 14 women)
      presented with their clinical AT at their redo procedure 7.7+/-4.4 months after
      initial de novo CAF ablation. A total of 133 ATs (2.2+/-0.9 per patient) were
      mapped. Forty-four (72%) were due to reentry; 17 (28%) were focal ATs. Reentry
      ATs were mainly characterized as roof and perimitral flutter (43% and 34%,
      respectively). Focal ATs mainly originated from the great thoracic veins
      (pulmonary veins: 41%, coronary sinus: 23%). Forty-five (74%) patients had
      conduction recovery of at least 1 pulmonary vein (mean, 1.2+/-0.8). Overall, 124
      (93%) ATs could be ablated successfully. The mean procedure duration was 181+/-59
      minutes, with a mean fluoroscopy time of 45+/-21 minutes. After a mean follow-up
      of 21+/-4 months, 50 (82%) patients were free of any arrhythmia recurrences after
      a single redo procedure. CONCLUSIONS: Although late recurrent ATs may have
      complex mechanisms, catheter ablation guided exclusively by conventional
      techniques is highly effective with excellent acute and long-term success rates.

PMID- 20133934
TI  - Structural heterogeneity alone is a sufficient substrate for dynamic instability
      and altered restitution.
AB  - BACKGROUND: Marked changes in ventricular APD restitution and associated
      alternans rhythm have been demonstrated in structural heart disease (SHD).
      However, whether this is due to structural heterogeneity or regional variation in
      cellular properties remains uncertain. In this study, we address the hypothesis
      that the structural heterogeneity associated with SHD is sufficient to alter
      dynamic restitution and increase the probability of electric instability. METHODS
      AND RESULTS: Activation was simulated in a 14x14 mm(2) domain in the presence and
      absence (control) of a central region containing nonuniform discontinuities
      resembling patchy fibrosis. A modified LR1 cardiac activation model was used in a
      bidomain formulation with isotropic conductivities. Bipolar stimulation was
      imposed above the central region with coupling intervals decreasing progressively
      from 500 ms and then maintained at 105 ms. Structural discontinuities had little
      effect on electric activation at low stimulus rates, but activation time and APD
      distributions became highly nonuniform within and adjacent to the discontinuous
      region at high rates. Discordant APD alternans occurred in both "fibrosis" and
      control, but at lower stimulus rates and with markedly greater extent in the
      former. Tortuous conduction through the discontinuous region resulted in large
      fluctuations of diastolic intervals giving rise to regional electric instability,
      which modulates dynamic conduction velocity and APD restitution. This led to
      heterogeneous conduction block and reentry not observed in control. CONCLUSIONS:
      We show that structural discontinuities can amplify discordant alternans and
      provide a rate-dependent substrate for reentry. This work provides new insights
      into the mechanisms by which fibrosis may contribute to arrhythmogenesis.

PMID- 20133935
TI  - Developmental silencing of human zeta-globin gene expression is mediated by the
      transcriptional repressor RREB1.
AB  - The mammalian embryonic zeta-globin genes, including that of humans, are
      expressed at the early embryonic stage and then switched off during erythroid
      development. This autonomous silencing of the zeta-globin gene transcription is
      probably regulated by the cooperative work of various protein-DNA and protein
      protein complexes formed at the zeta-globin promoter and its upstream enhancer
      (HS-40). We present data here indicating that a protein-binding motif, ZF2,
      contributes to the repression of the HS-40-regulated human zeta-promoter activity
      in erythroid cell lines and in transgenic mice. Combined site-directed
      mutagenesis and EMSA suggest that repression of the human zeta-globin promoter is
      mediated through binding of the zinc finger factor RREB1 to ZF2. This model is
      further supported by the observation that human zeta-globin gene transcription is
      elevated in the human erythroid K562 cell line or the primary erythroid culture
      upon RNA interference (RNAi)(2) knockdown of RREB1 expression. These data
      together suggest that RREB1 is a putative repressor for the silencing of the
      mammalian zeta-globin genes during erythroid development. Because zeta-globin is
      a powerful inhibitor of HbS polymerization, our experiments have provided a
      foundation for therapeutic up-regulation of zeta-globin gene expression in
      patients with severe hemoglobinopathies.

PMID- 20133936
TI  - The microtubule-associated histone deacetylase 6 (HDAC6) regulates epidermal
      growth factor receptor (EGFR) endocytic trafficking and degradation.
AB  - Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase with
      tubulin deacetylase activity, and it binds dynein motors. Recent studies revealed
      that microtubule acetylation affects the affinity and processivity of microtubule
      motors. These unique properties implicate a role for HDAC6 in intracellular
      organelle transport. Here, we show that HDAC6 associates with the endosomal
      compartments and controls epidermal growth factor receptor (EGFR) trafficking and
      degradation. We found that loss of HDAC6 promoted EGFR degradation.
      Mechanistically, HDAC6 deficiency did not cause aberrant EGFR internalization and
      recycling. Rather, it resulted in accelerated segregation of EGFR from early
      endosomes and premature delivery of EGFR to the late endosomal and lysosomal
      compartments. The deregulated EGFR endocytic trafficking was accompanied by an
      increase in microtubule-dependent movement of EGFR-bearing vesicles, revealing a
      novel regulation of EGFR vesicular trafficking and degradation by the microtubule
      deacetylase HDAC6.

PMID- 20133937
TI  - Inhibiting TRAF2-mediated activation of NF-kappaB facilitates induction of AP-1.
AB  - The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4
      thiadiazolidine (P(3)-25) is known to possess anti-bacterial, anti-fungal, and
      anti-tubercular activities. In this report, we provide evidence that P(3)-25
      inhibits NF-kappaB, known to induce inflammatory and tumorigenic responses. It
      activates AP-1, another transcription factor. It inhibits TRAF2-mediated NF
      kappaB activation but not TRAF6-mediated NF-kappaB DNA binding by preventing its
      association with TANK (TRAF for NF-kappaB). It facilitates binding of MEKK1 with
      TRAF2 and thereby activates JNK and AP-1. We provide evidence, for the first
      time, that suggests that the interaction of P(3)-25 with TRAF2 leads to
      inhibition of the NF-kappaB pathway and activation of AP-1 pathway. These results
      suggest novel approaches to design of P(3)-25 as an anti-cancer/inflammatory drug
      for therapy through regulation of the TRAF2 pathway.

PMID- 20133938
TI  - Neuropilin 1 directly interacts with Fer kinase to mediate semaphorin 3A-induced
      death of cortical neurons.
AB  - Neuropilins (NRPs) are receptors for the major chemorepulsive axonal guidance cue
      semaphorins (Sema). The interaction of Sema3A/NRP1 during development leads to
      the collapse of growth cones. Here we show that Sema3A also induces death of
      cultured cortical neurons through NRP1. A specific NRP1 inhibitory peptide
      ameliorated Sema3A-evoked cortical axonal retraction and neuronal death.
      Moreover, Sema3A was also involved in cerebral ischemia-induced neuronal death.
      Expression levels of Sema3A and NRP1, but not NRP2, were significantly increased
      early during brain reperfusion following transient focal cerebral ischemia. NRP1
      inhibitory peptide delivered to the ischemic brain was potently neuroprotective
      and prevented the loss of motor functions in mice. The integrity of the injected
      NRP1 inhibitory peptide into the brain remained unchanged, and the intact peptide
      permeated the ischemic hemisphere of the brain as determined using MALDI-MS-based
      imaging. Mechanistically, NRP1-mediated axonal collapse and neuronal death is
      through direct and selective interaction with the cytoplasmic tyrosine kinase
      Fer. Fer RNA interference effectively attenuated Sema3A-induced neurite
      retraction and neuronal death in cortical neurons. More importantly, down
      regulation of Fer expression using Fer-specific RNA interference attenuated
      cerebral ischemia-induced brain damage. Together, these studies revealed a
      previously unknown function of NRP1 in signaling Sema3A-evoked neuronal death
      through Fer in cortical neurons.

PMID- 20133939
TI  - Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its
      ubiquitination.
AB  - The alpha subunit of stimulatory G protein (G alpha(s)) activates adenylyl
      cyclase, which catalyzes cAMP production, and regulates many physiological
      aspects, such as cardiac regulation and endocrine systems. Ric-8B (resistance to
      inhibitors of cholinesterase 8B) has been identified as the G alpha(s)-binding
      protein; however, its role in G(s) signaling remains obscure. In this study, we
      present evidence that Ric-8B specifically and positively regulates G(s) signaling
      by stabilizing the G alpha(s) protein. An in vitro biochemical study suggested
      that Ric-8B does not possess guanine nucleotide exchange factor activity.
      However, knockdown of Ric-8B attenuated beta-adrenergic agonist-induced cAMP
      accumulation, indicating that Ric-8B positively regulates G(s) signaling.
      Interestingly, overexpression and knockdown of Ric-8B resulted in an increase and
      a decrease in the G alpha(s) protein, respectively, without affecting the G
      alpha(s) mRNA level. We found that the G alpha(s) protein is ubiquitinated and
      that this ubiquitination is inhibited by Ric-8B. This Ric-8B-mediated inhibition
      of G alpha(s) ubiquitination requires interaction between Ric-8B and G alpha(s)
      because Ric-8B splicing variants, which are defective for G alpha(s) binding,
      failed to inhibit the ubiquitination. Taken together, these results suggest that
      Ric-8B plays a critical and specific role in the control of G alpha(s) protein
      levels by modulating G alpha(s) ubiquitination and positively regulates G(s)
      signaling.

PMID- 20133940
TI  - Nucleoporin translocated promoter region (Tpr) associates with dynein complex,
      preventing chromosome lagging formation during mitosis.
AB  - Gain or loss of whole chromosomes is often observed in cancer cells and is
      thought to be due to aberrant chromosome segregation during mitosis. Proper
      chromosome segregation depends on a faithful interaction between spindle
      microtubules and kinetochores. Several components of the nuclear pore
      complex/nucleoporins play critical roles in orchestrating the rapid remodeling
      events that occur during mitosis. Our recent studies revealed that the
      nucleoporin, Rae1, plays critical roles in maintaining spindle bipolarity. Here,
      we show association of another nucleoporin, termed Tpr (translocated promoter
      region), with the molecular motors dynein and dynactin, which both orchestrate
      with the spindle checkpoints Mad1 and Mad2 during cell division. Overexpression
      of Tpr enhanced multinucleated cell formation. RNA interference-mediated
      knockdown of Tpr caused a severe lagging chromosome phenotype and disrupted
      spindle checkpoint proteins expression and localization. Next, we performed a
      series of rescue and dominant negative experiments to confirm that Tpr
      orchestrates proper chromosome segregation through interaction with dynein light
      chain. Our data indicate that Tpr functions as a spatial and temporal regulator
      of spindle checkpoints, ensuring the efficient recruitment of checkpoint proteins
      to the molecular motor dynein to promote proper anaphase formation.

PMID- 20133941
TI  - The inorganic pyrophosphate transporter ANK preserves the differentiated
      phenotype of articular chondrocyte.
AB  - The differentiated phenotype of chondrocyte is lost in pathological situations
      and after interleukin (IL)-1beta challenge. Wnt proteins and the inorganic
      pyrophosphate (PP(i)) transporter Ank regulate the differentiation process in
      many cell types. We investigated the possible contribution of Ank and/or PP(i) to
      the maintenance of the differentiated chondrocyte phenotype with special care to
      Wnt signaling. Primary articular chondrocytes lost their phenotype upon IL-1beta
      challenge, with cessation of type II collagen and Sox-9 expression. Ank
      expression and PP(i) transport were strongly reduced by IL-1beta, whereas Wnt-5a
      was the only Wnt protein increased. Transient overexpression of Ank counteracted
      most of IL-1beta effects on Type II collagen, Sox-9, and Wnt-5a expression. When
      resting chondrocytes were transfected with a siRNA against Ank, this reproduced
      the phenotype induced by IL-1beta. In both cases, no markers for hypertrophic
      chondrocytes were detected. The conditioned supernatant from chondrocytes knocked
      down for Ank contained Wnt-5a, which activated Tcf/Lef reporter plasmids and
      promoted translocation of beta-catenin into the nucleus without activating the c
      Jun N-terminal kinase (JNK) pathway. Supplementation with PP(i) compensated for
      most effects of Ank deficiency on Type II collagen, Sox-9, and Wnt-5 expression,
      both in IL-1beta and Ank knock-down conditions. Phenotype changes induced by IL
      1beta were also supported by activation of the JNK pathway, but this latter was
      not sensitive to PP(i) supplementation. Altogether our data demonstrate that the
      transport of PP(i) by ANK contributed to the maintenance of the differentiated
      phenotype of chondrocyte by controlling the canonical Wnt pathway in a Wnt-5a
      dependent manner.

PMID- 20133942
TI  - Structure-based engineering of species selectivity in the interaction between
      urokinase and its receptor: implication for preclinical cancer therapy.
AB  - The high affinity interaction between the urokinase-type plasminogen activator
      (uPA) and its glycolipid-anchored receptor (uPAR) is decisive for cell surface
      associated plasminogen activation. Because plasmin activity controls fibrinolysis
      in a variety of pathological conditions, including cancer and wound healing,
      several intervention studies have focused on targeting the uPA.uPAR interaction
      in vivo. Evaluations of such studies in xenotransplanted tumor models are,
      however, complicated by the pronounced species selectivity in this interaction.
      We now report the molecular basis underlying this difference by solving the
      crystal structure for the murine uPA.uPAR complex and demonstrate by extensive
      surface plasmon resonance studies that the kinetic rate constants for this
      interaction can be swapped completely between these orthologs by exchanging only
      two residues. This study not only discloses the structural basis required for a
      successful rational design of the species selectivity in the uPA.uPAR
      interaction, which is highly relevant for functional studies in mouse models, but
      it also suggests the possible development of general inhibitors that will target
      the uPA.uPAR interaction across species barriers.

PMID- 20133943
TI  - Regulation of CD1 antigen-presenting complex stability.
AB  - For major histocompatibility complex class I and II molecules, the binding of
      specific peptide antigens is essential for assembly and trafficking and is at the
      center of their quality control mechanism. However, the role of lipid antigen
      binding in stabilization and quality control of CD1 heavy chain (HC).beta(2)
      microglobulin (beta(2)m) complexes is unclear. Furthermore, the distinct
      trafficking and loading routes of CD1 proteins take them from mildly acidic pH in
      early endososmal compartments (pH 6.0) to markedly acidic pH in lysosomes (pH
      5.0) and back to neutral pH of the cell surface (pH 7.4). Here, we present
      evidence that the stability of each CD1 HC.beta(2)m complex is determined by the
      distinct pH optima identical to that of the intracellular compartments in which
      each CD1 isoform resides. Although stable at acidic endosomal pH, complexes are
      only stable at cell surface pH 7.4 when bound to specific lipid antigens. The
      proposed model outlines a quality control program that allows lipid exchange at
      low endosomal pH without dissociation of the CD1 HC.beta(2)m complex and then
      stabilizes the antigen-loaded complex at neutral pH at the cell surface.

PMID- 20133944
TI  - c-Cbl promotes T cell receptor-induced thymocyte apoptosis by activating the
      phosphatidylinositol 3-kinase/Akt pathway.
AB  - The ability of thymocytes to assess T cell receptor (TCR) signaling strength and
      initiate the appropriate downstream response is crucial for determining their
      fate. We have previously shown that a c-Cbl RING finger mutant knock-in mouse, in
      which the E3 ubiquitin ligase activity of c-Cbl is inactivated, is highly
      sensitive to TCR-induced death signals that cause thymic deletion. This high
      intensity signal involves the enhanced tyrosine phosphorylation of the mutant c
      Cbl protein promoting a marked increase in the activation of Akt. Here we show
      that this high intensity signal in c-Cbl RING finger mutant thymocytes also
      promotes the enhanced induction of two mediators of TCR-directed thymocyte
      apoptosis, Nur77 and the pro-apoptotic Bcl-2 family member, Bim. In contrast, a
      knock-in mouse harboring a mutation at Tyr-737, the site in c-Cbl that activates
      phosphatidylinositol 3-kinase, shows reduced TCR-mediated responses including
      suppression of Akt activation, a reduced induction of Nur77 and Bim, and greater
      resistance to thymocyte death. These findings identify tyrosine-phosphorylated c
      Cbl as a critical sensor of TCR signal strength that regulates the engagement of
      death-promoting signals.

PMID- 20133945
TI  - A conserved PMK-1/p38 MAPK is required in caenorhabditis elegans tissue-specific
      immune response to Yersinia pestis infection.
AB  - Yersinia pestis has acquired a variety of complex strategies that enable the
      bacterium to overcome defenses in different hosts and ensure its survival and
      successful transmission. A full-genome microarray analysis on Caenorhabditis
      elegans infected with Y. pestis shows enrichment in genes that are markers of
      innate immune responses and regulated by a conserved PMK-1/p38 MAPK. Consistent
      with a role in regulating expression of immune effectors, inhibition of PMK-1/p38
      by mutation or RNA interference enhances susceptibility to Y. pestis. Further
      studies of mosaic animals where PMK-1/p38 is exclusively inhibited or
      overexpressed in a tissue-specific manner indicate that PMK-1/p38 controls
      expression of a CUB-like family of immune genes at the cell-autonomous level.
      Given the conserved nature of PMK-1/p38 MAPK-mediated signaling and innate immune
      responses, PMK-1/p38 MAPK may play a role in the immune response against Y.
      pestis in natural hosts.

PMID- 20133946
TI  - Ethanol alters endosomal recycling of human dopamine transporters.
AB  - Dynamic membrane trafficking of the monoamine dopamine transporter (DAT)
      regulates dopaminergic signaling. Various intrinsic and pharmacological
      modulators can alter this trafficking. Previously we have shown ethanol
      potentiates in vitro DAT function and increases surface expression. However, the
      mechanism underlying these changes is unclear. In the present study, we found
      ethanol directly regulates DAT function by altering endosomal recycling of the
      transporter. We defined ethanol action on transporter regulation by [(3)H]DA
      uptake functional analysis combined with biochemical and immunological assays in
      stably expressing DAT HEK-293 cells. Short-term ethanol exposure potentiated DAT
      function in a concentration-, but not time-dependent manner. This potentiation
      was accompanied by a parallel increase in DAT surface expression. Ethanol had no
      effect on function or surface localization of the ethanol-insensitive mutant
      (G130T DAT), suggesting a trafficking-dependent mechanism in mediating the
      ethanol sensitivity of the transporter. The ethanol-induced increase in DAT
      surface expression occurred without altering the overall size of DAT endosomal
      recycling pools. We found ethanol increased the DAT membrane insertion rate while
      having no effect on internalization of the transporter. Ethanol had no effect on
      the surface expression or trafficking of the endogenously expressing transferrin
      receptor, suggesting ethanol does not have a nonspecific effect on endosomal
      recycling. These results define a novel trafficking mechanism by which ethanol
      regulates DAT function.

PMID- 20133947
TI  - Phospholipase C activity affinity purifies with the Torpedo nicotinic
      acetylcholine receptor.
AB  - Nicotinic acetylcholine receptors mediate fast synaptic transmission by fluxing
      ions across the membrane in response to neurotransmitter binding. We show here
      that during affinity purification of the nicotinic acetylcholine receptor from
      Torpedo, phosphatidic acid, but not other anionic or zwitterionic phospholipids,
      is hydrolyzed to diacylglycerol. The phospholipase C activity elutes with the
      acetylcholine receptor and is inhibited by a lipid phosphate phosphohydrolase
      inhibitor, sodium vanadate, but not a phosphatidate phosphohydrolase inhibitor, N
      ethylmaleimide. Further, the hydrolysis product of phosphatidic acid,
      diacylglycerol, enhances the functional capabilities of the acetylcholine
      receptor in the presence of anionic lipids. We conclude that a phospholipase C
      activity, which appears to be specific for phosphatidic acid, is associated with
      the nicotinic acetylcholine receptor. The acetylcholine receptor may directly or
      indirectly influence lipid metabolism in a manner that enhances its own function.

PMID- 20133948
TI  - Three different and tissue-specific NAD-malic enzymes generated by alternative
      subunit association in Arabidopsis thaliana.
AB  - The Arabidopsis thaliana genome contains two genes encoding the mitochondrial NAD
      malic enzyme (NAD-ME), NAD-ME1 (At2g13560) and NAD-ME2 (At4g00570). The
      characterization of recombinant NAD-ME1 and -2 indicated that both enzymes
      assemble as active homodimers; however, a heterodimeric enzyme (NAD-MEH) can also
      be detected by electrophoretic studies. To analyze the metabolic contribution of
      each enzymatic entity, NAD-MEH was obtained by a co-expression-based recombinant
      approach, and its kinetic and regulatory properties were analyzed. The three NAD
      MEs show similar kinetic properties, although they differ in the regulation by
      several metabolic effectors. In this regard, whereas fumarate activates NAD-ME1
      and CoA activates NAD-ME2, both compounds act synergistically on NAD-MEH
      activity. The characterization of two chimeric enzymes between NAD-ME1 and -2
      allowed specific domains of the primary structure, which are involved in the
      differential allosteric regulation, to be identified. NAD-ME1 and -2 subunits
      showed a distinct pattern of accumulation in the separate components of the
      floral organ. In sepals, the NAD-ME1 subunit is present at a slightly higher
      proportion than the NAD-ME2 subunit, and thus, NAD-MEH and NAD-ME1 act in concert
      in this tissue. On the other hand, NAD-ME2 is the only isoform present in
      anthers. In view of the different properties of NAD-ME1, -2, and -H, we suggest
      that mitochondrial NAD-ME activity may be regulated by varying native association
      in vivo, rendering enzymatic entities with distinct allosteric regulation to
      fulfill specific roles. The presence of three different NAD-ME entities, which
      originate by alternative associations of two subunits, is suggested to be a novel
      phenomenon unique to plant mitochondria.

PMID- 20133949
TI  - Impaired cardiovascular function in primary biliary cirrhosis.
AB  - Cardiovascular system dysregulation in the form of autonomic dysfunction is
      common at all stages of the disease process in the autoimmune liver disease
      primary biliary cirrhosis (PBC) and associates with the symptom of fatigue. The
      mechanisms underpinning autonomic dysfunction in PBC are, however, at present
      unclear. In this study we set out to explore, for the first time, cardiac
      structure and function in PBC using impedance cardiography (ICG) and magnetic
      resonance methodologies. ICG was assessed beat to beat in response to orthostasis
      (by head-up tilt) in age and sex case-matched high-fatigue and low-fatigue PBC
      groups (assessed by Fatigue Impact Scale), normal control subjects (n = 15 each
      group) and a liver disease control cohort (primary sclerosing cholangitis).
      Cardiac structure and bioenergetics were examined in 15 of the PBC subjects and 8
      of the normal control subjects by magnetic resonance spectroscopy and cine
      imaging. Capacity of the left ventricle to respond to orthostasis [left
      ventricular ejection time (LVET)] was impaired in PBC compared with matched
      normal control subjects (P = 0.05). This was a PBC-specific phenomenon unrelated
      to fatigue status. PBC patients exhibited significantly lower cardiac muscle
      phosphocreatine-to-ATP ratio (PCr/ATP ratio; measure of cardiac bioenergetic
      integrity) compared with control subjects (P < 0.01). PCr/ATP <1.6 (indicative of
      increased risk of death in cardiomyopathy) was present in 6/15 (40%) PBC patients
      (0/8 control subjects; P < 0.05). Cardiac structure and function were similar in
      all measures of left ventricular morphology between control subjects and PBC. The
      close relationship between PCr/ATP and LVET seen in normal subjects (r(2) = 0.6;
      P < 0.05) was lost in PBC patients, a finding compatible with myocardial
      dysfunction. Significant correlation was seen between fatigue severity in PBC and
      fall in cardiac output on orthostasis (r(2) = 0.25; P = 0.005). Our findings
      suggest the presence of altered myocardial function in PBC. Autonomic
      "dysfunction" may, rather than being an abnormal process, represent a
      compensatory mechanism to increase cardiac return to mitigate these effects.

PMID- 20133950
TI  - Comparison of human and porcine gastric clasp and sling fiber contraction by M2
      and M3 muscarinic receptors.
AB  - To compare the gastroesophageal junction of the human with the pig, M(2) and M(3)
      receptor densities and the potencies of M(2) and M(3) muscarinic receptor subtype
      selective antagonists were determined in gastric clasp and sling smooth muscle
      fibers. Total muscarinic and M(2) receptors are higher in pig than human clasp
      and sling fibers. M(3) receptors are higher in human compared with pig sling
      fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer
      M(3) receptors than sling fibers in both humans and pigs. Similar to human clasp
      fibers, pig clasp fibers contract significantly less than pig sling fibers.
      Analysis of the methoctramine Schild plot suggests that M(2) receptors are
      involved in mediating contraction in pig clasp and sling fibers. Darifenacin
      potency suggests that M(3) receptors mediate contraction in pig sling fibers and
      that M(2) and M(3) receptors mediate contraction in pig clasp fibers. Taken
      together, the data suggest that both M(2) and M(3) muscarinic receptors mediate
      the contraction in both pig clasp and sling fibers similar to human clasp and
      sling fibers.

PMID- 20133951
TI  - Insulin-like growth factors are more effective than progastrin in reversing
      proapoptotic effects of curcumin: critical role of p38MAPK.
AB  - Progastrin and insulin-like growth factors (IGFs) stimulate hyperproliferation of
      intestinal epithelial cells (IECs) via endocrine/paracrine routes;
      hyperproliferation is a known risk factor for colon carcinogenesis. In the
      present study, inhibitory potency of curcumin in the presence or absence of
      progastrin and/or IGF-II was examined. Progastrin and IGF-II significantly
      increased proliferation of an immortalized IEC cell line, IEC-18, whereas
      curcumin decreased the proliferation in a dose-dependent manner. IGF-II was
      significantly more effective than progastrin in reversing antiproliferative
      effects of curcumin and reversed proapoptotic effects of curcumin by >80%;
      progastrin was relatively ineffective toward reversing proapoptotic effects of
      curcumin. IEC-18 clones were generated to overexpress either progastrin (IEC-PG)
      or hIGF-II (IEC-IGF). Proliferation of IEC-PG and IEC-IGF clones was increased,
      compared with that of control clones. Curcumin significantly reduced
      proliferation of IEC-PG, but not IEC-IGF, clones. Similarly, a human colon cancer
      cell line, Caco-2 (which expresses autocrine IGF-II), was relatively resistant to
      inhibitory effects of curcumin. However, Caco-2 cells treated with anti-IGF-II
      antibodies were rendered sensitive to inhibitory effects of curcumin. Significant
      differences in inhibitory potency of curcumin against PG- vs. IGF-II-stimulated
      growth of IEC-18 cells were not reflected by differences in curcumin-mediated
      inhibition of activated (phosphorylated) ERKs/IKK(alpha/beta)/p65NF-kappaB and c
      Src in wild-type (wt)IEC-18 cells, in response to the two growth factors.
      Surprisingly, curcumin was almost ineffective in reducing IGF-II-stimulated
      activation of p38MAPK but significantly reduced progastrin-stimulated
      phosphorylation of p38. Treatment with a p38MAPK inhibitor resulted in loss of
      protective effects of IGF-II against inhibitory effects of curcumin. These novel
      findings suggest that growth factor profile of patients and tumors may dictate
      inhibitory potency of curcumin and that combination of curcumin + p38MAPK
      inhibitor may be required for reducing hyperproliferative or tumorigenic response
      of IECs to endocrine and autocrine IGFs.

PMID- 20133952
TI  - Cooperation between HNF-1alpha, Cdx2, and GATA-4 in initiating an enterocytic
      differentiation program in a normal human intestinal epithelial progenitor cell
      line.
AB  - In the intestinal epithelium, the Cdx, GATA, and HNF transcription factor
      families are responsible for the expression of differentiation markers such as
      sucrase-isomaltase. Although previous studies have shown that Cdx2 can induce
      differentiation in rat intestinal IEC-6 cells, no data are available concerning
      the direct implication of transcription factors on differentiation in human
      normal intestinal epithelial cell types. We investigated the role of Cdx2, GATA
      4, and HNF-1alpha using the undifferentiated human intestinal epithelial crypt
      cell line HIEC. These transcription factors were tested on proliferation and
      expression of polarization and differentiation markers. Ectopic expression of
      Cdx2 or HNF-1alpha, alone or in combination, altered cell proliferation abilities
      through the regulation of cyclin D1 and p27 expression. HNF-1alpha and GATA-4
      together induced morphological modifications of the cells toward polarization,
      resulting in the appearance of functional features such as microvilli. HNF-1alpha
      was also sufficient to induce the expression of cadherins and
      dipeptidylpeptidase, whereas in combination with Cdx2 it allowed the expression
      of the late differentiation marker sucrase-isomaltase. Large-scale analysis of
      gene expression confirmed the cooperative effect of these factors. Finally,
      although DcamKL1 and Musashi-1 expression were downregulated in differentiated
      HIEC, other intestinal stem cell markers, such as Bmi1, were unaffected. These
      observations show that, in cooperation with Cdx2, HNF-1alpha acts as a key factor
      on human intestinal cells to trigger the onset of their functional
      differentiation program whereas GATA-4 appears to promote morphological changes.

PMID- 20133953
TI  - Distribution of Borna disease virus antigen and RNA in tissues of naturally
      infected bicolored white-toothed shrews, Crocidura leucodon, supporting their
      role as reservoir host species.
AB  - Borna disease is a severe viral-induced disorder of the central nervous system of
      horses, sheep, and a few other animal species, occurring in certain areas of
      central Europe. Pathogenesis and epidemiology of natural Borna disease virus
      (BDV) infections are still not fully understood; several unique epidemiologic
      features, however, point toward the existence of BDV reservoir populations other
      than the final hosts. In this study, 69 mice and 12 shrews were trapped and
      examined. The virus distribution was investigated in detail in 2 BDV-positive
      bicolored white-toothed shrews, Crocidura leucodon, by immunohistochemistry and
      TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR). RT-PCR
      amplification products were sequenced, and the sequences were compared. These
      shrews had been collected in a BDV-endemic geographical region using live traps
      and did not show obvious clinical or pathological disease signs. BDV antigen and
      nucleic acid were identified in several organs, including the brain, mainly in
      nerve tissue and neurons, respectively, but also in parenchymal cells (eg,
      hepatocytes, Leydig cells) and epithelial cells, particularly of the respiratory
      and urogenital tract.

PMID- 20133954
TI  - Hemophagocytic histiocytic sarcoma in a Japanese black cow.
AB  - At necropsy, an 11-year-old Japanese Black cow with anemia, leukocytopenia, and
      progressive hind limb ataxia had marked diffuse splenomegaly and multiple masses
      in the thoracic vertebrae. Histologically, neoplastic erythrophagocytic
      histiocytes were in the splenic red pulp, vertebral masses, and blood vessels of
      the liver and lungs. The spinal cord was compressed by the vertebral masses.
      Clinicopathological, macroscopic, and histologic findings were consistent with
      hemophagocytic histiocytic sarcoma. Vertebral involvement with spinal cord
      compression and resultant hind limb ataxia is an unusual presentation for this
      tumor, which has been described mainly in dogs and cats.

PMID- 20133956
TI  - Prevalence and neurodegenerative or other associations with olfactory impairment
      in an older community.
AB  - OBJECTIVE: To determine the prevalence of olfactory impairment and its
      associations with neurodegenerative and other conditions in older adults. METHOD:
      1,636 participants (>/=60 years) enrolled in the Blue Mountains Eye Study (2002
      2004) were analyzed. Olfaction was assessed by the San Diego Odor Identification
      Test and used to classify mild impairment (4 or 5), moderate impairment (</=3),
      or any impairment (<6). RESULTS: Prevalent olfactory impairment was 27.0%. After
      multivariate adjustment, the likelihood increased twofold with each decade of
      life after 60 years and was higher in men than women. Olfactory impairment and
      body mass index (BMI) were inversely associated. Persons with Parkinson's disease
      and cognitive impairment had an increased likelihood of mild and moderate
      olfactory impairment. DISCUSSION: Over one in four older persons had olfactory
      impairment. The prevalence was higher in men, increased with age and decreasing
      BMI, and was higher among persons with Parkinson's disease and cognitive
      impairment.

PMID- 20133957
TI  - Preventable hospitalization among nursing home residents: varying views between
      medical directors and directors of nursing regarding determinants.
AB  - OBJECTIVE: To compare the perception of the determinants of preventable
      hospitalization among nursing home residents by surveying medical directors (MDs)
      and directors of nursing (DONs). METHODS: A survey (N = 52) was completed in
      January 2008. Data included resource availability, determinants of
      hospitalization, and nursing home practice. Multivariate linear regression
      examined the associations between potential determinants and preventable
      hospitalization. RESULTS: Four significant determinants perceived by MDs to
      influence preventable hospitalization: MD/nurse practitioner (NP) access by
      pager, family preferences, access to medical history and lab/ electrocardiograph
      (EKG) reports, and physicians better paid to manage acutely ill residents (R(2) =
      .58). None of these factors were echoed by DONs (R(2) = .15). Whereas DONs
      perceived stat lab results on weekends were associated with increased
      hospitalization (p = .03), MDs did not (p = .28). CONCLUSIONS: Our analysis
      showed that communication and consensus are important factors in the hospital
      transfer decision and that the discord in perceptions among MDs and DONs may
      complicate interventions to reduce preventable hospitalization.

PMID- 20133958
TI  - Basic anthropometry and health status of elderly: findings of the Maracaibo Aging
      Study.
AB  - OBJECTIVE: Determine basic anthropometry for elderly participants in a Venezuelan
      community and compare results for subgroups with different health status. METHOD:
      Standardized anthropometric, nutritional, neurological, neuropsychiatric, and
      cardiovascular assessments generated data on weight, height, and body mass index
      (BMI) by sex and age for the total sample, for normative groups without health
      problems that might impact anthropometry, and for reference groups with no major
      health problems. Centile curves of anthropometric measurements versus age are
      determined for women and men in the normative group. RESULTS: Mean weight and
      height are significantly different between sexes, but not BMI. All three
      parameters show gradual declines with age. The mean 90% central interval for BMI
      in the normative and reference groups is 20-29 kg/m(2). CONCLUSION: The
      anthropometric data for healthy elderly Venezuelans can be used in monitoring
      anthropometric changes and disease risk analysis for this population and possibly
      for other Latin American populations.

PMID- 20133959
TI  - Considering the pedophile subculture online.
AB  - The development of the Internet and computer-mediated communications has fostered
      the growth of a wide range of deviant sexual behaviors along with deviant
      subcultures that support and approve of these behaviors. Some of these practices
      pose little risk to public safety, though acts such as pedophilia and the
      creation and distribution of child pornography have significant negative
      ramifications for victims. A growing literature has examined the function of the
      Internet for child pornography distribution, social networks of pedophiles, and
      tactics of child solicitation. Few, however, have explored the utility of the
      Internet to develop a subculture of pedophiles and its role in fostering
      attitudes and justifications for relationships with children. This study will
      explore the subcultural norms and enculturation of the pedophile community using
      a qualitative analysis of five Web forums run by and for pedophiles. The findings
      suggest that the values of the pedophile culture support and encourage emotional
      and, in some cases, sexual relationships with boys and girls in virtual and real
      settings. Implications for the study of pedophiles and the role of the Internet
      are explored.

PMID- 20133960
TI  - An exploratory study of victim resistance in child sexual abuse: offender modus
      operandi and victim characteristics.
AB  - The use of self-protection strategies and related situation in rape has been
      studied by several scholars. The circumstances in which children are more likely
      to resist sexual victimization have, however, not been studied. This study
      examines the association between offence-related factors-specifically, the
      preoffence situation, the modus operandi strategies adopted by offenders, and
      victim characteristics-and victim resistance in sexual offences against
      children.The sample consisted of 94 adult offenders convicted of having committed
      a sexual offence against a child (or adolescent) of 16 years of age or younger
      and who agreed to provide confidential self-report data concerning their
      offending behavior and victim resistance actions. Victim resistance strategies
      were regrouped into three categories, namely, physical resistance, forceful
      verbal resistance, and nonforceful verbal resistance. The total number of
      resistance strategies was also used in the analyses. Overall, the age of the
      victim was found to be related to nonforceful verbal resistance, and violence was
      related to all forms of resistance.Younger girls were found to be more likely to
      employ nonforceful verbal resistance than older girls and to use a greater number
      of strategies as well. To provide reliable knowledge to build on for reducing the
      risk of child sexual abuse, this study suggests the need for prevention programs
      to include empirical findings regarding the circumstances in which children are
      more likely to resist sexual victimization.

PMID- 20133961
TI  - Examining the influence of denial, motivation, and risk on sexual recidivism.
AB  - This study examined the relationship between denial, motivation, static risk
      (Risk Matrix 2000), and sexual recidivism. Denial was measured in three ways: A
      Denial Index (resulting from the combination of several measures of different
      aspects of denial), Absolute Denial, and Denial of Risk. Motivation for treatment
      was also examined. Logistic regression analyses in a sample of 180 sex offenders
      using a fixed 10-year follow-up found that risk moderated the relationships
      between the Denial Index, Absolute Denial, and sexual recidivism. In particular,
      among high-risk offenders, denial predicted decreased sexual recidivism. An
      opposite pattern was observed for the low-risk offenders who were in denial,
      although these differences were not significant. In terms of Denial of Risk,
      those who were denying they presented a future risk for offending (i.e., higher
      on Denial of Risk) were less likely to reoffend than those who reported seeing
      themselves as presenting a high risk. Motivation for treatment was positively
      correlated with recidivism, but the effect disappeared once static risk was
      controlled.

PMID- 20133962
TI  - A controlled evaluation of a prison-based sexual offender intervention program.
AB  - The effectiveness of a prison-based cognitive behavioral program designed to
      modify psychological risk factors associated with sexual offending was evaluated.
      The Irish Prison Service Sexual Offender Intervention Programme, is a manualized
      10-month Cognitive Behaviour Therapy [CBT] program involving three 2-hour group
      sessions per week, which are facilitated by a team of clinical psychologists and
      probation officers. Improvements in 38 consecutive referrals to the program were
      compared with the status of 38 untreated offenders who were similar in marital
      status, age when they left school, occupational status prior to imprisonment,
      offence type, presence of previous convictions, and current sentence length. All
      research participants completed the same assessment protocol, which evaluated
      psychological factors associated with sexual offending at times equivalent to pre
      and postintervention. Compared with the untreated control group, program
      participants showed statistically significant improvement on some but not all
      self-report measures of cognitive distortions, empathy, interpersonal skills,
      self-regulation, and relapse prevention. Motivation to change among the untreated
      control group was not associated with change in psychological functioning in the
      absence of the assistance of the treatment program. Implications for sexual
      offender intervention delivery are considered.

PMID- 20133963
TI  - Theory of mind in men who have sexually offended against children: a U.K.
      comparison study between child sex offenders and nonoffender controls.
AB  - Child sex offenders are typically characterized by empathy problems, cognitive
      distortions, and social skills deficits. It has been proposed that these
      characteristics may be attributable to an underlying impairment in the ability to
      attribute mental states to others (i.e., theory of mind).This study compared a
      group of nonincarcerated child sex offenders (n = 46) with a group of community
      controls ( n = 46) matched for age, socioeconomic status, ethnicity, and status
      as a parent. Both groups completed two measures of theory of mind: one that
      measures the ability to infer the mental states of adults and another that
      measures the ability to infer the mental states of children. Offenders were
      significantly worse than controls at inferring the mental states of adults. In
      contrast, there were no differences between offenders and controls in their
      ability to infer the mental states of children. The results are discussed with
      regard to psychological theory, clinical work, and future research.

PMID- 20133964
TI  - Pharmacokinetics and safety of long-acting testosterone undecanoate injections in
      hypogonadal men: an 84-week phase III clinical trial.
AB  - Currently available testosterone (T) injections in the United States are
      administered at 2-3 weekly intervals. Less frequent injections with favorable
      serum T pharmacokinetics would benefit hypogonadal men. The objective of this
      study is to assess the pharmacokinetics of long-acting testosterone undecanoate
      (TU) intramuscular (IM) injection in hypogonadal men. An unblinded, multicenter
      phase 3 clinical trial was conducted in 31 academic centers and contract research
      organizations. Males (130) more than 18 years of age with serum total T < 300
      ng/dL were enrolled and received 750-mg injections of TU at weeks 0 and 4 and
      every 10 weeks thereafter for 9 injections over 84 weeks. The main outcome
      variables were serum total T, free T, dihydrotestosterone (DHT), estradiol (E(2))
      levels, and safety parameters. After the first injection, patients maintained
      average trough T concentrations in the adult male range (300-1000 ng/dL or 10.4
      34.7 nmol/L) before each injection and at multiple time points measured after the
      third and fourth injections. Serum free T, DHT, and E(2) levels and their ratios
      to serum T remained relatively consistent once steady state was attained. TU
      injections were generally well tolerated, with safety profiles similar to other T
      replacement. We conclude that hypogonadal patients treated for 84 weeks with a
      750-mg IM injection of TU every 10 weeks demonstrated average concentrations of
      T, its metabolites (DHT and E(2)), and ratios--DHT:T and E(2):T--within the adult
      male reference range at all time points measured. TU injections would be an
      acceptable alternative to the currently available 2-3 weekly injectables.

PMID- 20133965
TI  - A rare case of serous papillary cystadenocarcinoma of the testis.
AB  - The serous papillary cystadenocarcinoma is a rare testicular neoplasm, which
      depending on the histological features can behave more or less aggressive, thus
      leading to a not always predictable prognosis. We present diagnosis and treatment
      of a case of serous papillary cystadenocarcinoma of the testis with associated
      adherent mass to the tunica albuginea, which compressed the parenchyma without
      infiltrating it.

PMID- 20133966
TI  - Replication needed to distinguish alterations in cell ratios, the frequency of
      individual stages of the cycle of the seminiferous epithelium, or the appearance
      of abnormalities in the testes of rodents, rabbits, or humans.
AB  - The typical levels of inherent variability among untreated sexually mature
      rodents, rabbits, or men were determined for several endpoints used to
      characterize spermatogenesis. The latter included germ cell:germ cell and germ
      cell:Sertoli cell ratios, the frequency of specific stages of the cycle of the
      seminiferous epithelium, and the appearance of a variety of testicular
      abnormalities. Based on this variability, the number of replicates needed to
      provide future experiments of a predictable power and sensitivity was estimated.
      Replication requirements differed greatly as a function of species and/or among
      specific endpoints within a single species. In addition, the replication needed
      to provide robust experiments was substantially greater than that employed in
      most investigations. The application of these findings during the design and
      interpretation of future experiments was discussed.

PMID- 20133967
TI  - Spermatozoa bound to solid state hyaluronic acid show chromatin structure with
      high DNA chain integrity: an acridine orange fluorescence study.
AB  - During human spermiogenesis, the elongated spermatids undergo a plasma membrane
      remodeling step that facilitates formation of the zona pellucida and hyaluronic
      acid (HA) binding sites. Various biochemical sperm markers indicated that human
      sperm bound to HA exhibit attributes similar to that of zona pellucida-bound
      sperm, including minimal DNA fragmentation, normal shape, and low frequency of
      chromosomal aneuploidies. In this work, we tested the hypothesis that HA-bound
      sperm would be enhanced in sperm of high DNA chain integrity and green acridine
      orange fluorescence (AOF) compared with the original sperm in semen. Sperm DNA
      integrity in semen and in their respective HA-bound sperm fractions was studied
      in 50 men tested for fertility. In the semen samples, the proportions of sperm
      with green AOF (high DNA integrity) and red AOF (DNA breaks) were 54.9% +/- 2.0%
      and 45.0% +/- 1.9%, whereas in the HA-bound sperm fraction, the respective
      proportions were 99% and 1.0%, respectively. The data indeed demonstrated that HA
      shows a high degree of selectivity for sperm with high DNA integrity. These
      findings are important from the points of view of human sperm DNA integrity,
      sperm function, and the potential efficacy of HA-mediated sperm selection for
      intracytoplasmic sperm injection.

PMID- 20133968
TI  - Investigation of human testis protein heterogeneity using 2-dimensional
      electrophoresis.
AB  - The testis is the male gonad responsible for spermatogenesis and male hormone
      secretion. The complicated processes of spermatogenesis and steroidogenesis
      determine the complexity of protein expression control in the testis. In this
      study, the heterogeneity of human testis proteins was investigated using 2
      dimensional gel electrophoresis. A total of 847 protein spots corresponding to
      462 unique proteins were identified successfully by mass spectrometry. Notable
      heterogeneity was evidenced by the presence of more than 1 spot with different
      molecular weight and/or Isoelectric point values for each of 180 different
      proteins. Analysis of the detected peptides of these proteins indicated that this
      heterogeneity was partly the result of alternative splicing and/or proteolysis.
      SP_PIR_Keywords analysis suggested that alternative initiation sites and various
      forms of posttranslational modification may also contribute toward this
      heterogeneity. Using Pro-Q Diamond phosphostain, 68 spots representing 52
      proteins were stained, confirming the presence of phosphorylated forms of these
      proteins in the human testis. These data were used to establish a proteome
      reference database, which can be accessed over the Internet
      (http://reprod.njmu.edu.cn/2d). This database provides an initial reference map
      of the human testis and serves as a useful resource for comparative proteomics
      studies of the human testis under normal and pathological states. The abundant
      protein heterogeneity observed in this study and further investigation of its
      biological significance will contribute toward understanding protein expression
      regulation in the human testis and will generate insight into the molecular
      mechanism of spermatogenesis.

PMID- 20133969
TI  - Effectiveness of combined modality radiotherapy of orthotopic human squamous cell
      carcinomas in Nu/Nu mice using cetuximab, tirapazamine and MnSOD-plasmid liposome
      gene therapy.
AB  - Hypoxic regions limit the radiocontrollability of head and neck carcinomas.
      Whether or not combinations of plasmid/liposome mediated overexpression of normal
      tissue protective manganese superoxide dismutase (MnSOD), cetuximab (C225), and
      the hypoxic cytotoxin tirapazamine (TPZ) enhanced radiotherapeutic effects was
      tested in a CAL-33 orthotopic mouse cheek tumor model. The tumor volume continued
      to increase in the control (untreated) mice, with a ninefold increase by 10 days
      when the tumors exceeded 2 cm(3). The mice receiving 14 Gy only showed reduced
      tumor growth to 3.1+/-0.1 fold at day 10. The mice receiving MnSOD-PL, C225, TPZ
      plus 14 Gy had the best outcome with 0.7+/-0.1 fold increase in tumor volume by
      10 days (p=0.015) compared to irradiation only. The addition of MnSOD-PL, TPZ,
      and C225 to irradiation optimized the therapeutic ratio for the local control of
      hypoxic region-containing CAL-33 orthotopic tumors.

PMID- 20133970
TI  - Screening of antimicrobial agents for in vitro radiation protection and
      mitigation capacity, including those used in supportive care regimens for bone
      marrow transplant recipients.
AB  - Antibiotic and antifungal agents used in supportive care regimens for bone marrow
      transplantation recipients contribute to a significant dose-modifying effect of
      otherwise lethal total body irradiation. To determine whether drugs used in
      supportive care and other commonly used antibiotics such as tetracycline function
      as radiation protectors or damage mitigators in vitro, 13 drugs were tested for
      radiation protection and radiation damage mitigation of 32D cl 3 hematopoietic
      progenitor cells in clonagenic survival curves in vitro. Antibiotic/Antifungal
      agents including cilastatin, amikacin, ceftazidine, vancomycin, tetracycline,
      doxycycline, ciprofloxacin, metronidazole, methacycline, minocycline,
      meclocycline, oxytetracycline and rolitetracycline were added in 1, 10, or 100
      micromolar concentrations to murine interleukin-3-dependent hematopoietic
      progenitor cell line 32D cl 3 cells either before or after irradiation of 0 to 8
      Gy. Control irradiated 32D cl 3 cells showed radiosensitivity comparable to
      freshly explanted mouse marrow hematopoietic progenitor cells (D(0) 1.1+/-0.1 Gy,
      N 1.5+/-0.4). Positive control GS-nitroxide JP4-039 (known radiation mitigator)
      treated 32D cl 3 cells were radioresistant (D(0) 1.2+/-0.1, N 5.8+/-2.4
      (p=0.009)). Of the 13 drugs tested, tetracycline was found to be a significant
      radiation mitigator (D(0) 0.9+/-0.1, N 13.9+/-0.4 (p=0.0027)). Thus, the
      radiation dose-modifying effect of some antibiotics, but not those currently used
      in the supportive care (antibiotic/antifungal regimens) for marrow transplant
      patients, may act as radiation damage mitigators for hematopoietic cells as well
      as decreasing the growth and inflammatory response to microbial pathogens.

PMID- 20133971
TI  - Rational targeting in acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (ARL) is characterized by the nearly homogeneous
      expression of the fusion oncogenic protein PML-RARalpha and the testis-specific
      cyclin A1 protein, which are implicated in its pathogenesis. PML-RARalpha binds
      all-trans retinoic acid with high affinity inducing granulocytic differentiation
      and remission. Current approaches with high doses of single or combined all-trans
      retinoic acid and chemotherapeutic agents, though relatively efficacious in the
      beginning, are highly toxic with severe side-effects (retinoic acid syndrome) and
      are followed by relapse in a high proportion of patients. Here it is proposed
      that targeting APL with low levels of all-trans retinoic acid combined with small
      molecule inhibitors of cyclin-dependent kinases may have the potential to be
      equally or more efficacious as any of the current single or combined agent
      approaches, affording reduced toxicity and relapse rates.

PMID- 20133972
TI  - Effect of contact with titanium alloys on the proliferation of mouse osteoblastic
      cells in culture.
AB  - This study was aimed at studying the effect of contact with titanium alloy plates
      of different surface textures on the proliferative capability of mouse
      osteoblastic MC3T3-E1 cells. First, the proliferation characteristics of MC3T3-E1
      cells were investigated. MC3T3-E1 cells showed a high capacity for proliferation
      and survived for a long period even under nutritionally starved conditions.
      During logarithmic cell growth, the consumption of Ser, Gln, Val, Ile and Leu
      increased time-dependently. Contact with an hydoxyapatite (HA)-coated titanium
      alloy plate resulted in the increase in the recovery of cells from the plate by
      trypsin, and an increase in the consumption of these amino acids, suggesting
      enhanced cell proliferation. On the contrary, contact with the sandblasted and
      anodized titanium alloy plates resulted in the reduction of the recovery of the
      cells from the plate, but a slight increase in the amino acid consumption,
      suggesting the tight adhesion of the cells to the plates. This study demonstrates
      that the present method, based on the amino acid consumption of the cells, is
      useful for monitoring the cell proliferative capability, without detachment of
      the cells from the plate. This method may be applicable to the study of the
      interaction between cells and metal plates.

PMID- 20133973
TI  - Hormetic response of cultured normal and tumor cells to 2-aminotropone
      derivatives.
AB  - We have recently reported that out of twenty benzo[b]cyclohept[e][1,4]oxazines
      and their S-analogs, and 2-aminotropone derivatives, 7-bromo-2-(4-hydroxyanilino)
      tropone and 4-isopropyl-2-(2-hydroxyanilino)tropone showed the highest tumor
      specificity in human oral squamous cell carcinoma cell lines. To gain more
      insight into the anti-tumor actions of these compounds, whether they induce the
      growth stimulation effect observed at low concentrations, known as hormesis, was
      investigated using a total of ten human normal and tumor cultured cells. The
      tumor-specificity of both compounds became apparent 48 hours after the start of
      treatment of the cells with these compounds and reached a maximum level at 72 and
      96 hours. On the other hand, their growth stimulatory effects were most prominent
      at 24 hours, especially in normal skin and lung fibroblasts, but rapidly
      disappeared with prolonged incubation time (48-96 hours). These data suggest the
      occurrence of a hormetic response only at restricted times and concentrations as
      has been previously reported, although the biological significance is yet to be
      elucidated.

PMID- 20133974
TI  - CD40L-transfected myeloma cells transfer prolonged immunity in vivo.
AB  - BACKGROUND: In a large number of patients with multiple myeloma, chemotherapy is
      the only therapeutic option. During recent years, major effort has been put into
      immunotherapeutic approaches for this malignancy. MATERIALS AND METHODS: In this
      study, wild-type (wt) myeloma cells (5x10(5)) were injected subcutaneously into
      Balb/c mice. CD40L-transfected myeloma cells (5x10(5)) were subsequently injected
      intratumorally into the established (>100 mm(3)) wt tumor nodules. Overall
      survival and tumor growth were measured. RESULTS: Out of eight animals receiving
      wt tumor cells, one died prior to the formation of a solid tumor nodule.
      Following the CD40L-transfected myeloma cell injection, stable complete remission
      at day 60 with all the animals surviving resulted. On day 60, a re-challenge was
      performed with wt myeloma cells. No tumor growth was observed after 120 days out
      of seven remaining animals, one died. CONCLUSION: Intratumoral injection of CD40L
      transfected myeloma cells induces complete tumor remission and long lasting
      immunity against tumor recurrence.

PMID- 20133975
TI  - Resveratrol activation of nitric oxide synthase in rabbit brain synaptosomes:
      singlet oxygen (1O2) formation as a causative factor of neurotoxicity.
AB  - In the present study it was shown that resveratrol (3,4,5-trihydroxystilbene), an
      efficient light-absorbing molecule, during its transition from trans to cis
      configuration under UV light, transfers its energy of excitation to triplet
      oxygen to produce singlet oxygen ((1)O(2)). This transition is prevented by
      Trolox, a quencher of singlet oxygen. In the presence of a stable amount of
      nitrosoglutathione, UV-irradiated resveratrol reacts with nitric oxide (NO)
      originating from the nitrosoglutathione to produce peroxynitrite (ONOO(-)). Beta
      carotene, acting as a quencher of (1)O(2), prevents the transition of resveratrol
      from trans to cis. Beta-carotene also prevents DNA damage induced by the (1)O(2).
      NO synthase (NOS) activity in synaptosomes isolated from rabbit brain increased
      approximately three-fold by resveratrol and the NO released was converted to
      ONOO(-). Resveratrol increased the lipid fluidity of synaptosomal plasma
      membranes. These changes suggest that the incorporation of resveratrol into
      synaptosomal plasma membranes causes an up-regulation of NO synthase. On the
      other hand, the simultaneous ONOO(-) and (1)O(2) formation may cause disturbances
      in transmembrane signal transduction leading to neurotoxicity. The present study
      concerning the behavior of resveratrol with respect to its structure and
      potential prooxidant-antioxidant function provides important new clues as to the
      role of this fascinating molecule in pathophysiology.

PMID- 20133976
TI  - Inhibition of prostaglandin E2 production by flavone and its related compounds.
AB  - We have previously reported that among 12 major ingredients of Sairei-to,
      Scutellariae radix inhibited prostaglandin E(2) (PGE(2)) production by
      lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells more
      efficiently than other ingredients, and wogonin, a major flavonoid from
      Scutellariae radix, showed greater inhibitory activity and membrane permeability
      than baicalein and baicalin. Here the effects of six other flavonoids, with
      similar structures, on membrane permeability and PGE(2) production were
      investigated. 7-Methoxyflavone inhibited the LPS-stimulated PGE(2) production to
      the greatest extent, followed by flavone>wogonin (5,7-dihydroxy-8
      methoxyflavone)>> 7,8-dimethoxyflavone>chrysin (5,7-dihydroxyflavone)> baicalein
      (5,6,7-trihydroxyflavone)>>chromone. 7-Methoxyflavone also showed the highest
      membrane permeability, followed by flavone>chrysin>7,8-dimethoxy
      flavone>wogonin>baicalein. When PGE(2) inhibitory activity was expressed per
      molecule incorporated into the cells, wogonin produced the greatest inhibition,
      further substantiating its anti-inflammatory potency.

PMID- 20133977
TI  - Comparison of the effect of orally administered soluble beta-(1-3),(1-6)-D-glucan
      and of G-CSF on the recovery of murine hematopoiesis.
AB  - Beta-glucans are branched fungal polysaccharide compounds with pleiotropic
      activating effects on cells of the immune and the hematopoietic system. In this
      study, the hematopoiesis-promoting effect of an orally administered soluble beta
      (1-3),(1-6)-D-glucan and of intravenously (i.v.) injected recombinant human
      granulocyte colony-stimulating factor (G-CSF/filgrastim) was tested in
      cyclophosphamide (CY)-conditioned mice. Both agents were administered for 5
      consecutive days following treatment with CY. When G-CSF and the carbohydrate
      compound were co-administered, a small but non-significant increase of
      granulopoiesis compared to G-CSF alone was detected. beta-Glucan alone failed to
      augment granulopoiesis in the peripheral blood of CY-treated mice. However, both
      G-CSF and beta-glucan significantly enhanced the recovery of monocytes in the
      peripheral blood of leukopenic mice when orally administered as single agents. In
      conclusion, the present study provides further evidence of a stimulatory function
      of orally administered beta-glucans on monocyte production and shows a weak
      additive effect on granulopoiesis when co-administered with G-CSF into leukopenic
      mice.

PMID- 20133978
TI  - Comparison of lipid profiles in relation to APOB EcoRI polymorphism in obese
      children with hyperlipidemia.
AB  - BACKGROUND: We aimed to evaluate apolipoprotein B-100 (APOB) EcoRI polymorphism
      and plasma lipid parameters together in children and adolescents. This is the
      first such study in Turkey to determine possible relationships of these
      parameters. MATERIALS AND METHODS: Three separate groups were studied: a group of
      obese children with hyperlipidemia, a group of obese children without
      hyperlipidemia, and a group of healthy children neither with hyperlipidemia nor
      obesity. Polymerase chain reaction (PCR), denaturating gradient gel
      electrophoresis (DGGE) and automatic sequence analysis techniques were used.
      Sequencing results were examined by Proseq and BioEdit computer programmes.
      RESULTS: Mutant A allele was not observed in the healthy control group, whereas
      it was more frequent in the hyperlipidemic obese children; the GA genotype was
      correlated with total and low density lipoprotein-cholesterol levels. CONCLUSION:
      In this study, we suggest that obese child patients having the A allele could
      have a higher risk for developing hyperlipidemia.

PMID- 20133979
TI  - CYP17 (T-34C) and CYP19 (Trp39Arg) polymorphisms and their cooperative effects on
      breast cancer susceptibility.
AB  - BACKGROUND: Breast cancer is the commonest cancer among women in industrialized
      countries. Most sporadic breast carcinomas are likely to be caused by low
      penetrance genes. Genes encoding enzymes involved in estrogen and carcinogen
      metabolism are among these low-penetrance genes. In this study, for the first
      time the T/C (A1/A2) polymorphism at the 5' untranslated region (UTR) of CYP17
      and the Arg/Trp (T/C) polymorphism at codon 39 of CYP19 among genes regulating
      endogenous estrogen levels was studied. PATIENTS AND METHODS: Fifty-five female
      breast cancer patients and ninety-one controls took part in the study. DNA was
      extracted from paraffin-embedded tissues for the patients and from blood cells
      for the controls. The distribution of genotypes was determined using polymerase
      chain reaction (PCR) and restriction fragment length polymorphism (RFLP)
      techniques. RESULTS: The frequency of the TC genotype of CYP19 was significantly
      higher in the patient group (p<0.001, kappa(2): 12.31, OR: 7.30, 95% CI: 2.29
      25.64). CYP17 frequencies were similar to those in Caucasian populations. In
      combined analysis, when the high risk alleles were evaluated together, the
      results reached significance (p=0.006, kappa(2)=7.01, OR: 2.53, %95 CI: 1.26
      5.07) for the A2 allele of CYP17 and the C allele of CYP19, being more frequent
      in the patient group compared to the control. The risk possesed by the TC varient
      of CYP19 was reduced when evaluated with A1, the protective allele of CYP17
      (p=0.082). The cumulative protective effects of both A1 allele and the TT
      genotype were ascertained to occur significantly less frequently in the patient
      group (p=0.001, kappa(2): 10.53, OR: 8.47, %95 CI: 1.9-37.04). CONCLUSION: The
      results were consistent with the individual studies of CYP17 and CYP19 in the
      literature, however, in combined analysis of the alleles of the two genes, the
      frequency of high risk alleles was higher and the frequencies of low risk alleles
      were lower in the patient group. The CYP17 A1 + CYP19 TT haplotype may be
      protective for breast cancer.

PMID- 20133980
TI  - Relationship between psychoncology and psychoneuroendocrinoimmunology (PNEI):
      enhanced T-regulatory lymphocyte activity in cancer patients with self
      punishement, evaluated by Rorschach test.
AB  - BACKGROUND: Psychological studies have documented the presence of a self
      punishment profile in cancer patients. Recent immuno-oncological studies have
      shown that within the group of CD4(+) cells, which play a fundamental role in the
      generation of anticancer immunity, there is a subtype of cells that in contrast
      mediates the suppression of the anticancer immunity, the so-called T-regulatory
      cells (T-reg), which may be identified as CD4(+)CD25(+) cells. PATIENTS AND
      METHODS: On this basis, we performed a psychoncological study to evaluate
      CD4(+)CD25(+) cell numbers in relation to the response to Rorschach's test in a
      group of 30 cancer patients suffering from the most frequent tumor histotypes.
      RESULTS: Normal values obtained in our laboratory (95% confidence limits) of T
      reg lymphocytes and CD4(+)/CD4(+)CD25(+) were <240/mm(3) and >4mm(3),
      respectively. The psychological profile of self-punishment was found in 18/30
      patients (60%). The percentage of patients with abnormally high CD4(+)CD25(+)
      values observed in the group with self-punishment was significantly higher than
      that found in patients without self punishment (11/18 vs. 3/12 (25%), p<0.05). In
      the same way, the percentage of patients with abnormally low CD4(+)/CD4(+)CD25(+)
      ratios was significantly higher in the group with self-punishment (16/18 vs.
      4/12, p<0.01). The mean numbers of T-reg lymphocytes observed in the group with
      self-punishment was significantly higher than that found in patients who had no
      self-punishment (314+/-39 vs. 173+/-27, p<0.05). In addition, the mean CD4(+)/
      CD4(+)CD25(+) ratio was significantly lower in patients with self-punishment than
      in the other group (2.6+/-0.2 vs. 5.2+/-0.8, p<0.025). On the contrary, no
      significant difference was seen in the mean number of CD4(+) lymphocytes.
      CONCLUSION: The study suggests that self-punishment may inhibit the generation of
      an effective anticancer immune response by stimulating the activation and
      proliferation of T-reg lymphocytes, which in turn stimulate tumor dissemination
      by suppressing anticancer immunity. The abnormally high number of T-reg
      lymphocytes in patients with self-punishment would suggest a specific immune
      alteration, as suggested by the evidence of a normal profile for other immune
      parameters, such as total CD4(+) lymphocytes.

PMID- 20133981
TI  - Treatment of peritoneal carcinomatosis from colonic cancer by cytoreduction,
      peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). Experience
      of ten years.
AB  - INTRODUCTION: Peritoneal carcinomatosis (PC) is one of the routes of
      dissemination of abdominal neoplasms and is generally considered a lethal
      disease, with a poor prognosis by conventional chemotherapeutic treatments. While
      systemic chemotherapy has little impact on the treatment of peritoneal disease,
      some centers have reported encouraging results with cytoreduction and
      hyperthermic intraperitoneal chemotherapy (HIPEC). This approach is based on
      surgical cytoreduction of the primary tumour, peritonectomy (stripping of
      implants on the peritoneal surface) and HIPEC. The rationale of this treatment,
      after macroscopic disease removal, is to obtain an elevated and persistent drug
      concentration in the peritoneal cavity, with limited systemic effects. Many
      studies have reported encouraging results on overall survival (OS) and the
      disease-free interval in patients affected by PC. PATIENTS AND METHODS: From
      October 1997 to November 2008, 411 operations for PC were performed in our
      institution; in 232 cases, cytoreduction plus HIPEC was carried out. Out of 72
      operations for colonic cancer: 40 cytoreductions plus HIPEC, 12 cytoreductions+
      EPIC (early postoperative intraperitoneal chemotherapy) and 16 debulking or
      explorative laparoscopies/laparotomies were performed. For the present study, the
      40 patients who had undergone cytoreduction plus HIPEC for PC of colorectal
      cancer (CRC) were considered. RESULTS: The complication rate was 55% (22/40) and
      mortality rate 2.5% (1/40). The specific features of both groups were considered
      for the survival curves and complication rates, with special reference to the
      peritoneal carcinomatosis index (PCI; range 0, absence of disease to 39) and
      completeness of cytoreduction score (CCR; 0, no residual tumor, to CCR 3,
      residual nodules greater than 25 mm). In Group A, patients operated on prior to
      2002, the median survival time was 16.7 months compared to 24.6 months for Group
      B, those operated on after 2002. The poor survival of Group A seemed to be
      related to higher PCI and CCR scores. CONCLUSION: Correct patient selection based
      on a maximum PCI of 16, associated with complete cytoreduction (CCR-0), produced
      encouraging results in our experience. To improve this encouraging survival
      outcome, it is very important to unify the surgical experience of expertise
      centres. Our results also suggest the need for an integrated approach to this
      condition to identify the correct aspect of the surgical domain and results that
      may be influencing the prognosis and the evolution of this patients.

PMID- 20133982
TI  - Familial chronic lymphocytic leukemia in Norway and Denmark. Comments on
      pleiotropy and birth order.
AB  - AIM: To investigate the genetics of chronic lymphocytic leukemia (CLL). MATERIALS
      AND METHODS: In 56 (7%) out of 800 CLL patients with concomitant malignant
      hematological disease, 51 families and 141 cases were ascertained. RESULT: 106
      cases (75%) of CLL, 27 cases (19%) of nonCLL and 8 cases (6%) of
      myeloproliferative disorders. Paternal disease was transmitted primarily to the
      youngest sons in the sibship while maternal disease was transmitted equally to
      all sibs, demonstrated by means of matrix conjugation and confirmed with Cox
      regression on parity and birth order (maternal-offspring combination: relative
      risk (RR), 95% confidence interval (CI)=1.47 (0.89 - 2.43), p=0.12, compared with
      paternal-offspring combination: RR=3.25, 95% CI=(1.57-6.72), p<0.001). The B-cell
      expression in familial and sporadic CLL was indistinguishable. CONCLUSION:
      Parental genomic imprinting is pointed out as one possible mechanism behind this
      non-Mendelian genomic output.

PMID- 20133983
TI  - Radioguided surgery and systemic radionuclide therapy of neuroendocrine tumours.
AB  - Neuroendocrine tumours (NETs) may be fatal, though at a significantly slower pace
      than their exocrine counterparts. Nuclear medicine procedures for diagnosis and
      treatment of NETs are based on expression of somatostatin receptors. Radioguided
      surgery is a new method for diagnosing and treating many tumours and uses
      introperative gamma probes. The use and development of intraoperative gamma
      probes in the last 10 years has enabled the development of minimally invasive
      procedures in oncological surgery, with an improvement in both the survival rate
      and the quality of life. Systemic therapy with radiolabeled somatostatin
      analogues is a promising new tool in the management of patients with inoperable
      or metastatic NETs. In terms of tumour regression, the results obtained are
      encouraging.

PMID- 20133984
TI  - Gradual loss of functional gap junction within progression of colorectal cancer -
      a shift from membranous CX32 and CX43 expression to cytoplasmic pattern during
      colorectal carcinogenesis.
AB  - The aim of this study was the assessment of expression and location of CX32 and
      CX43 in colorectal adenomas and carcinomas as well as analysis of expression of
      these proteins in association with clinical and pathological features of tumors
      and evaluation of mutual relationships between CX32 and CX43. PATIENTS AND
      METHODS: The study included 151 primary colorectal carcinoma and 71 colorectal
      adenomas. The control group comprised 30 colon samples. Connexins were detected
      with immunohistochemistry. RESULTS: There was a lack of membranous distribution
      of connexins or a shift from moderately membranous immunoreactivity to
      predominantly cytoplasmic accumulation of CX32 and CX43 in studied colon tumors.
      Mentioned alterations were found in adenomas and augmented in cancer. Expression
      of Cx32 was significantly associated with grading of colorectal cancer,
      implicating a role of intracellular CX32 in regulation of tumor growth and
      differentiation. A strong correlation was present between CX32 and CX43 in node
      positive cases and absent from node-negative ones. CONCLUSION: To our knowledge,
      our study is the first illustration for a gradual loss of functional gap
      junctions within progression of colorectal neoplasia. An intracellular location
      of connexins, the site of their common and the most frequent detection within
      cancer cells in our study may be of significance. Independently of its role in
      functional gap-junctions, cytoplasmic CX32 could be involved in cancer
      differentiation, resulting in a higher rate of CX32 positive moderately
      differentiated tumors (G3) than poorly differentiated CX32-positive ones (G3).

PMID- 20133985
TI  - Synchronous presentation of GISTs and other primary neoplasms: a single center
      experience.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are common mesenchymal
      neoplasms of the digestive tract and may occasionally arise within the abdomen
      without gastrointestinal tract connection. GISTs have recently attracted
      widespread interest because of the development of effective targeted molecular
      agents against it. While synchronous occurrence of a GIST with a tumor of
      different histogenesis was thought to be very rare, it is now apparent that they
      are more common than previously believed. PATIENTS AND METHODS: We report our
      experience with GISTs and also six cases of GIST coexisting with other primary
      neoplasms. Using immunohistochemistry and mutational analysis, a possible
      correlation was investigated. A review of the literature was also conducted.
      RESULTS: There were no significant differences in the immumohistochemical and
      molecular profile between single GISTs and GISTs coexisting with other tumors,
      nor was there any mutational correlation between GISTs and the coexistent tumors
      of different histogenesis regarding KIT and PDGFRA genes. CONCLUSION: Further
      molecular biology studies are required in order to investigate thoroughly the
      simultaneous development of tumors with different histotypes.

PMID- 20133986
TI  - Immune response parameters during labor and early neonatal life.
AB  - AIM: Selected cytokines, associated with Th1 and Th2 immune response and
      inflammation, were studied in order to evaluate the relation between their
      release into maternal and neonatal circulation, during labour, and after birth,
      in comparison with those in adults. MATERIALS AND METHODS: Cytokine
      concentrations were determined by very sensitive immunoassays, in maternal serum
      (MS), umbilical cord (UC), neonatal serum, the 1st (1N) and 5th (5N) day
      postpartum and in adult controls. RESULTS: Both IL-2 and IL-4 cytokine
      concentrations in UC were markedly elevated, compared to adult and MS ones. IL-2
      decreased significantly in 5N, while IL-4 remained unchanged. IFN-gamma UC values
      were significantly lower than those in adults and MS, increasing significantly in
      5N. Neonatal serum sIL-2R and sIL-4R were markedly higher than those in adults
      and MS. IL-1beta, IL-6, sIL-6R, sTNFRI and sTNFRII concentrations in MS and all
      with TNF-alpha in neonatal serum were significantly higher than in adults. IFN
      gamma, IL-1beta, IL-6, TNF-alpha, IL-2R, IL-4R concentrations in MS, 1N and 5N
      were dependent on the mode of delivery. CONCLUSION: The results of this
      comparative study are indicative for a meaningful role for the studied cytokines
      and their receptors in: i) the development of neonatal immune system, ii) the
      regulation of immune response during labour and early life, and iii) the
      initiation of the processes of labour.

PMID- 20133987
TI  - Cardiac echinococcosis, an unusual echocardiographic finding.

PMID- 20133988
TI  - Malaria elimination: when the tools are great but implementation falters.

PMID- 20133989
TI  - Is mosquito larval source management appropriate for reducing malaria in areas of
      extensive flooding in The Gambia? A cross-over intervention trial.
AB  - Larviciding to control malaria was assessed in rural areas with extensive
      seasonal flooding. Larval and adult mosquitoes and malaria incidence were
      surveyed routinely in four 100-km(2) areas either side of the Gambia River.
      Baseline data were collected in 2005. Microbial larvicide was applied to all
      water bodies by hand application with water-dispersible granular formulations and
      corn granules weekly from May to November in two areas in 2006 and in the other
      two areas in 2007 in a cross-over design. The intervention was associated with a
      reduction in habitats with late stage anopheline larvae and an 88% reduction in
      larval densities (P < 0.001). The effect of the intervention on mosquito
      densities was not pronounced and was confounded by the distance of villages to
      the major breeding sites and year (P = 0.002). There was no reduction in clinical
      malaria or anemia. Ground applications of non-residual larvicides with simple
      equipment are not effective in riverine areas with extensive flooding, where many
      habitats are poorly demarcated, highly mobile, and inaccessible on foot.

PMID- 20133990
TI  - Naturally acquired antibodies to Plasmodium vivax Duffy binding protein (DBP) in
      Brazilian Amazon.
AB  - Duffy binding protein (DBP), a leading malaria vaccine candidate, plays a
      critical role in Plasmodium vivax erythrocyte invasion. Sixty-eight of 366
      (18.6%) subjects had IgG anti-DBP antibodies by enzyme-linked immunosorbent assay
      (ELISA) in a community-based cross-sectional survey in the Brazilian Amazon
      Basin. Despite continuous exposure to low-level malaria transmission, the overall
      seroprevalence decreased to 9.0% when the population was reexamined 12 months
      later. Antibodies from 16 of 50 (36.0%) subjects who were ELISA-positive at the
      baseline were able to inhibit erythrocyte binding to at least one of two DBP
      variants tested. Most (13 of 16) of these subjects still had inhibitory
      antibodies when reevaluated 12 months later. Cumulative exposure to malaria was
      the strongest predictor of DBP seropositivity identified by multiple logistic
      regression models in this population. The poor antibody recognition of DBP
      elicited by natural exposure to P. vivax in Amazonian populations represents a
      challenge to be addressed by vaccine development strategies.

PMID- 20133991
TI  - Disentangling the effect of local and global spatial variation on a mosquito
      borne infection in a neotropical heterogeneous environment.
AB  - Mosquito-borne pathogen transmission exhibits spatial-temporal variability caused
      by ecological interactions acting at different scales. We used local spatial
      statistics and geographically weighted regression (GWR) to determine the spatial
      pattern of malaria incidence and persistence in northeastern Venezuela. Seven to
      11 hot spots of malaria transmission were detected by using local spatial
      statistics, although disease persistence was explained only for four of those hot
      spots. The GWR models greatly improved predictions of malaria risk compared with
      ordinary least squares (OLS) regression models. Malaria incidence was largely
      explained by the proximity to and number of Anopheles aquasalis habitats nearby
      (1-3 km), and low-elevation terrains. Disease persistence was associated with
      greater human population density, lower elevations, and proximity to aquatic
      habitats. However, there was significant local spatial variation in the
      relationship between malaria and environmental variables. Spatial modeling
      improves the understanding of the causal factors operating at several scales in
      the transmission of malaria.

PMID- 20133992
TI  - Burden of malaria during pregnancy at the time of IPTp/SP implementation in
      Gabon.
AB  - The new recommendations to prevent malaria in pregnant women have recently been
      implemented in Gabon. There is little information on the pregnancy indicators
      that are useful for their evaluation. A cross-sectional study for the assessment
      of the prevalence of peripheral, placental, and cord malaria and anemia among
      delivering women was performed at the largest public hospital of Gabon. Malaria
      prevalence was 34.4%, 53.6%, and 18.2% for maternal peripheral, placental, and
      cord blood respectively, with no difference between primigravidae and
      multigravidae. Submicroscopic infections were frequent and concerned all the
      positive cord samples. Maternal peripheral, late placental, and cord infections
      were all associated with a reduced mean birth weight in primigravidae (P = 0.02).
      Anemia prevalence was 53%, low birth rate was 13%, and prematurity was 25%. The
      use of intermittent preventive treatment with sulfadoxine-pyrimethamine (greater
      than or equal to one dose) combined with bed net was associated with a reduction
      in infection only in multigravidae and with a reduced risk of maternal anemia.

PMID- 20133993
TI  - Evaluation of a rapid qualitative enzyme chromatographic test for glucose-6
      phosphate dehydrogenase deficiency.
AB  - Rapid determination of glucose-6-phosphate dehydrogenase (G6PD) status is
      desirable when it is necessary to use a drug contraindicated in G6PD-deficient
      persons, such as use of primaquine for malaria prevention or treatment. The
      purpose of this study was to compare a new, rapid, qualitative enzyme
      chromatographic test for deficiency of G6PD to a standard reference method.
      Samples from 196 G6PD-normal persons and 50 G6PD-deficient persons were
      evaluated. The sensitivity of the experimental rapid test was 0.98 and the
      specificity was 0.98 using specimens preserved in heparin, and 0.98 and 0.97,
      respectively, for specimens preserved in EDTA. Positive and negative predictive
      values were 0.72 and 1.00, respectively, for the test for heparinized specimens
      and 0.65 and 1.00, respectively, for the EDTA-preserved samples. This rapid test
      for G6PD deficiency is a sensitive method for screening of G6PD deficiency that
      requires minimal training and equipment and enables rapid identification of G6PD
      deficient persons.

PMID- 20133994
TI  - Assessment of fever in African children: implication for malaria trials.
AB  - We evaluated methods for assessing body temperature by comparing subjective
      assessment of fever by parents and doctors with objective axillary, tympanic, and
      rectal measurements of body temperature in 1000 children < or = 10-years-old who
      presented at outpatient clinics with recent history of fever. Sensitivity of
      subjective assessment of fever were higher at thresholds of > or = 38.3 degrees C
      with specificity as low as 60%. Axillary methods showed better specificity at
      fever thresholds of > 38.0 degrees C with maximum sensitivity of 63% at
      thresholds of > or = 37.5 degrees C. Bland-Altman analysis showed wide limits of
      agreement between objective methods of measurements: -1 degrees C to 3 degrees C
      for comparison of rectal and axillary, -1 degrees C to 2 degrees C for rectal and
      tympanic, and -1 degrees C to 2 degrees C for tympanic and axillary measurements.
      A choice of method to measure body temperature for diagnosis of fever in African
      children should be informed by a trade-off between its specificity and
      sensitivity that considers thresholds > 38.0 degrees C.

PMID- 20133995
TI  - Retinal hemorrhage in Plasmodium vivax malaria.
AB  - Retinal hemorrhage is a frequently observed sign in Plasmodium falciparum
      infection. In Plasmodium vivax infection, however, retinal hemorrhage is very
      rare; only five cases have been reported in the literature. In this case report,
      we review the literature and the case of 52-year-old man who had retinal
      hemorrhages in P. vivax infection. We analyzed the structural characteristics of
      the lesions using fluorescein angiography and spectral-domain optical coherence
      tomography. Physicians should be aware of the possibility of retinal hemorrhage
      in malaria patients, even those with P. vivax infection, and should consider a
      diagnosis of malaria in a patient with unexplained retinal hemorrhage and fever.

PMID- 20133996
TI  - High complexity of Plasmodium vivax infections in symptomatic patients from a
      rural community in central Vietnam detected by microsatellite genotyping.
AB  - Fourteen published and three newly identified polymorphic microsatellites were
      used to genotype 69 Plasmodium vivax samples obtained from 39 patients detected
      over a period of two years who lived in a rural community of central Vietnam. All
      samples were polyclonal with an average expected heterozygosity of 0.86. Among
      the 39 patients, 16 experienced 1-5 recurrent episodes of P. vivax malaria, most
      of them (83%) with a different genotype profile compared with previous
      infections. The minimal set of microsatellites required for differentiating the
      genotype profiles of the recurrent infections compared with the full set of 17
      microsatellites was explored. A combination of five markers was sufficient to
      identify all recurrent infections with an unrelated or different genotype profile
      compared with all previous episodes.

PMID- 20133997
TI  - A non-radioactive DAPI-based high-throughput in vitro assay to assess Plasmodium
      falciparum responsiveness to antimalarials--increased sensitivity of P.
      falciparum to chloroquine in Senegal.
AB  - The spread of Plasmodium falciparum drug resistance is outpacing new antimalarial
      development and compromising effective malaria treatment. Combination therapy is
      widely implemented to prolong the effectiveness of currently approved
      antimalarials. To maximize utility of available drugs, periodic monitoring of
      drug efficacy and gathering of accurate information regarding parasite
      sensitivity changes are essential. We describe a high-throughput, non
      radioactive, field-based assay to evaluate in vitro antimalarial drug sensitivity
      of P. falciparum isolates from 40 Senegalese patients. Compared with earlier
      years, we found a significant decrease in chloroquine in vitro and in genotypic
      resistances (> 50% and > 65%, respectively, in previous studies) with only 23% of
      isolates showing resistance. This is possibly caused by a withdrawal of
      chloroquine from Senegal in 2002. We also found a range of artemisinin responses.
      Prevalence of drug resistance is dynamic and varies by region. Therefore, the
      implementation of non-radioactive, robust, high-throughput antimalarial
      sensitivity assays is critical for defining region-specific prophylaxis and
      treatment guidelines.

PMID- 20133998
TI  - Identification of malaria retinopathy improves the specificity of the clinical
      diagnosis of cerebral malaria: findings from a prospective cohort study.
AB  - The diagnosis of cerebral malaria (CM) is difficult to confirm in endemic regions
      with limited neurodiagnostics. Accurate diagnoses are critical for trials and
      outcomes studies. Findings from an autopsy-based study suggest that identifying
      malaria retinopathy in children satisfying the standard clinical case definition
      of CM improves our ability to accurately diagnose CM in vivo. In a post hoc
      analysis of a prospective exposure-control study to evaluate CM as a risk factor
      for epilepsy, we stratified children meeting the standard case definition by
      their retinopathy status (presence versus absence) and compared these groups for
      pre-existing risk factors for epilepsy. We also compared them to the concurrently
      enrolled, non-comatose controls. Children meeting the standard case definition of
      CM who lacked malaria retinopathy had a higher prevalence of pre-existing
      developmental problems and family history of epilepsy. This subset of patients
      may represent children with a pre-existing propensity to adverse neurologic
      symptoms and outcomes.

PMID- 20133999
TI  - Geographic structure of Plasmodium vivax: microsatellite analysis of parasite
      populations from Sri Lanka, Myanmar, and Ethiopia.
AB  - Genetic diversity and population structure of Plasmodium vivax parasites can
      predict the origin and spread of novel variants within a population enabling
      population specific malaria control measures. We analyzed the genetic diversity
      and population structure of 425 P. vivax isolates from Sri Lanka, Myanmar, and
      Ethiopia using 12 trinucleotide and tetranucleotide microsatellite markers. All
      three parasite populations were highly polymorphic with 3-44 alleles per locus.
      Approximately 65% were multiple-clone infections. Mean genetic diversity (H(E))
      was 0.7517 in Ethiopia, 0.8450 in Myanmar, and 0.8610 in Sri Lanka. Significant
      linkage disequilibrium was maintained. Population structure showed two clusters
      (Asian and African) according to geography and ancestry. Strong clustering of
      outbreak isolates from Sri Lanka and Ethiopia was observed. Predictive power of
      ancestry using two-thirds of the isolates as a model identified 78.2% of isolates
      accurately as being African or Asian. Microsatellite analysis is a useful tool
      for mapping short-term outbreaks of malaria and for predicting ancestry.

PMID- 20134000
TI  - Environmental risk factors for the incidence of American cutaneous leishmaniasis
      in a sub-Andean zone of Colombia (Chaparral, Tolima).
AB  - Environmental risk factors for cutaneous leishmaniasis were investigated for the
      largest outbreak recorded in Colombia. The outbreak began in 2003 in Chaparral,
      and in the following five years produced 2,313 cases in a population of 56,228.
      Candidate predictor variables were land use, elevation, and climatic variables
      such as mean temperature and precipitation. Spatial analysis showed that
      incidence of cutaneous leishmaniasis was higher in townships with mean
      temperatures in the middle of the county's range. Incidence was independently
      associated with higher coverage with forest or shrubs (2.6% greater for each
      additional percent coverage, 95% credible interval [CI] = 0.5-4.9%), and lower
      population density (22% lower for each additional 100 persons/km(2), 95% CI = 7
      41%). The extent of forest or shrub coverage did not show major changes over
      time. These findings confirmed the roles of climate and land use in leishmaniasis
      transmission. However, environmental variables were not sufficient to explain the
      spatial variation in incidence.

PMID- 20134001
TI  - Leishmania infection: laboratory diagnosing in the absence of a "gold standard".
AB  - There is no gold standard for diagnosing leishmaniases. Our aim was to assess the
      operative validity of tests used in detecting Leishmania infection using samples
      from experimental infections, a reliable equivalent to the classic definition of
      gold standard. Without statistical differences, the highest sensitivity was
      achieved by protein A (ProtA), immunoglobulin (Ig)G2, indirect fluorescenece
      antibody test (IFAT), lymphocyte proliferation assay, quantitative real-time
      polymerase chain reaction of bone marrow (qPCR-BM), qPCR-Blood, and IgG; and the
      highest specificity by IgG1, IgM, IgA, qPCR-Blood, IgG, IgG2, and qPCR-BM.
      Maximum positive predictive value was obtained simultaneously by IgG2, qPCR
      Blood, and IgG; and maximum negative predictive value by qPCR-BM. Best positive
      and negative likelihood ratios were obtained by IgG2. The test having the
      greatest, statistically significant, area under the receiver operating
      characteristics curve was IgG2 enzyme-linked immunosorbent assay (ELISA). Thus,
      according to the gold standard used, IFAT and qPCR are far from fulfilling the
      requirements to be considered gold standards, and the test showing the highest
      potential to detect Leishmania infection is Leishmania-specific ELISA IgG2.

PMID- 20134002
TI  - Development of Cryptosporidium parvum-induced gastrointestinal neoplasia in
      severe combined immunodeficiency (SCID) mice: severity of lesions is correlated
      with infection intensity.
AB  - We reported previously that Cryptosporidium parvum was able to induce intestinal
      tumors in severe combined immunodeficiency (SCID) mice treated with corticoids.
      To further characterize this Cryptosporidium-induced cell transformation, SCID
      mice treated with dexamethasone were challenged with C. parvum oocysts, and
      euthanatized sequentially after infection for histologic examination. Ki-67 was
      used as a marker of cellular proliferation. Our previous results were confirmed,
      and it was also found that mice receiving higher inocula (10(6)-10(7))
      experienced more severe neoplastic development. Additionally, neoplastic changes
      were observed not only in the caecum but also in the stomach and duodenum of some
      animals. Interestingly, SCID mice (6/6) inoculated with 10(5)-10(7) oocysts
      showed high grade intraepithelial neoplasia or adenomas with high grade dysplasia
      in the caecum after Day 46 post-infection (PI). Immunohistochemistry for Ki-67
      staining indicated the neoplastic process associated to cryptosporidiosis, and
      evidenced the first immunohistochemical alterations at early stages of the
      process, even at 3 weeks PI.

PMID- 20134004
TI  - Histopathological, serological, and molecular confirmation of indigenous alveolar
      echinococcosis cases in Mongolia.
AB  - Alveolar echinococcosis cases diagnosed histopathologically in 2002, 2006, 2007,
      and 2009 in Ulaanbaatar, Mongolia were reconfirmed by evaluating the cytochrome c
      oxidase subunit I gene of mitochondrial DNA. The most recent three cases using
      paraffin-embedded and ethanol-fixed specimens revealed that one was of the
      "Asian" haplotype, whereas two others were of the "Inner Mongolian" type. All
      patients were born in the western provinces of Mongolia, they never resided
      outside of Mongolia, and they were given a preliminary diagnosis of malignant
      hepatic tumor or abscess. The most recent two cases were also confirmed
      serologically to be active alveolar echinococcosis.

PMID- 20134005
TI  - Efficacy of waterless hand hygiene compared with handwashing with soap: a field
      study in Dar es Salaam, Tanzania.
AB  - Effective handwashing with soap requires reliable access to water supplies.
      However, more than three billion persons do not have household-level access to
      piped water. This research addresses the challenge of improving hand hygiene
      within water-constrained environments. The antimicrobial efficacy of alcohol
      based hand sanitizer, a waterless hand hygiene product, was evaluated and
      compared with handwashing with soap and water in field conditions in Dar es
      Salaam, Tanzania. Hand sanitizer use by mothers resulted in 0.66 and 0.64 log
      reductions per hand of Escherichia coli and fecal streptococci, respectively. In
      comparison, handwashing with soap resulted in 0.50 and 0.25 log reductions per
      hand of E. coli and fecal streptococci, respectively. Hand sanitizer was
      significantly better than handwashing with respect to reduction in levels of
      fecal streptococci (P = 0.01). The feasibility and health impacts of promoting
      hand sanitizer as an alternative hand hygiene option for water-constrained
      environments should be assessed.

PMID- 20134006
TI  - Evaluation of a new disinfection approach: efficacy of chlorine and bromine
      halogenated contact disinfection for reduction of viruses and microcystin toxin.
AB  - Contaminated drinking water is responsible for causing diarrheal diseases that
      kill millions of people a year. Additionally, toxin-producing blue-green algae
      associated with diarrhea and neurologic effects continues to be an issue for many
      drinking water supplies. Disinfection has been used to reduce these risks. A
      novel gravity-fed household drinking water system with canisters containing N
      halamine bromine or chlorine media was challenged with MS2 bacteriophage and
      microcystin. Chlorine and bromine systems were effective against this virus, with
      an mean +/- SE reduction of 2.98 +/- 0.26 log(10) and 5.02 +/- 0.19 log(10),
      respectively. Microcystin toxin was reduced by 27.5% and 88.5% to overall mean +/
      SE concentrations of 1,600 +/- 98 ng/L and 259 +/- 50 ng/L for the chlorine and
      bromine canisters, respectively. Only the bromine units consistently produced
      microcystin effluent < 1,000 ng/L (the World Health Organization recommended
      level) when challenged with 2,500 ng/L and consistently surpassed the U.S.
      Environmental Protection Agency virus reduction goal of 99.99%.

PMID- 20134007
TI  - Estimating the scope of household water treatment in low- and medium-income
      countries.
AB  - For populations without reliable access to safe drinking water, household water
      treatment (HWT) provides a means of improving water quality and preventing
      disease. We extracted data on reported HWT practices from 67 national surveys and
      reports on the scope of HWT. An estimated 33.0% of the households (1.1 billion
      people) in these countries report treating their drinking water at home. The
      practice is widespread in the Western Pacific (66.8%) and Southeast Asia (45.4%)
      regions, and it is less common in the Eastern Mediterranean (13.6%) and Africa
      (18.2%). Boiling is the most dominant method with 21.0% of the study households
      (598 million people) using the method. Despite being at higher risk of waterborne
      disease because of lower coverage of improved water sources, African and rural
      households are less likely to practice HWT or use microbiologically adequate
      methods. Validation of the household surveys and further analysis of these data
      could help optimize HWT practices.

PMID- 20134008
TI  - Travel and travelers' diarrhea in patients with irritable bowel syndrome.
AB  - This study evaluated occurrence of travel and travelers' diarrhea in patients
      with irritable bowel syndrome (IBS). A survey was mailed to 591 patients of a
      clinical practice who had IBS. Based on survey responses, patients were
      categorized as having IBS, post-infectious IBS (PI-IBS), unclassified functional
      bowel disorder (UFBD), or post-infectious UFBD (PI-UFBD). Of 201 persons who
      returned questionnaires meeting inclusion criteria, 57.7%, 11.4%, 24.9%, and 6.0%
      had IBS, UFBD, PI-IBS, and PI-UFBD, respectively. Travel during six months before
      illness onset was more common in patients with PI-IBS or PI-UFBD than in persons
      with idiopathic IBS or UFBD (P = 0.006). Survey results demonstrated that 16.1%
      of post-infectious bowel disorder cases and 7.5% of overall IBS cases in a
      general medical population developed chronic disease within six months of an
      international trip. Symptoms of established functional bowel disorder in each
      clinical category were shown to worsen after travel-related acute diarrhea.

PMID- 20134009
TI  - Geographic information systems and applied spatial statistics are efficient tools
      to study Hansen's disease (leprosy) and to determine areas of greater risk of
      disease.
AB  - Applied Spatial Statistics used in conjunction with geographic information
      systems (GIS) provide an efficient tool for the surveillance of diseases. Here,
      using these tools we analyzed the spatial distribution of Hansen's disease in an
      endemic area in Brazil. A sample of 808 selected from a universe of 1,293 cases
      was geocoded in Mossoro, Rio Grande do Norte, Brazil. Hansen's disease cases were
      not distributed randomly within the neighborhoods, with higher detection rates
      found in more populated districts. Cluster analysis identified two areas of high
      risk, one with a relative risk of 5.9 (P = 0.001) and the other 6.5 (P = 0.001).
      A significant relationship between the geographic distribution of disease and the
      social economic variables indicative of poverty was observed. Our study shows
      that the combination of GIS and spatial analysis can identify clustering of
      transmissible disease, such as Hansen's disease, pointing to areas where
      intervention efforts can be targeted to control disease.

PMID- 20134010
TI  - The contribution of bats to leptospirosis transmission in Sao Paulo City, Brazil.
AB  - The biodiversity of potential leptospiral reservoir hosts is lower in urban than
      in rural environments. Previous data indicate the potential for bats to act as
      carriers of Leptospira in regions such as the Amazon of South America and in
      Australia. Yet, little is known about the contribution of bats to leptospirosis
      in urban environments in South America. This study aimed to test the hypothesis
      that bats infected with Leptospira are sources of leptospirosis transmission to
      humans in Sao Paulo City, Brazil. Six of 343 bats caught in different districts
      within the city of Sao Paulo (182 insectivorous, 161 frugivorous or
      nectarivorous) were polymerase chain reaction (PCR) positive for pathogenic
      Leptospira; no seropositive bats were found. That few renal carriers of
      Leptospira were found in the city of Sao Paulo suggests that bats are not
      important in the transmission of leptospirosis to humans in this, and possibly
      other urban settings.

PMID- 20134011
TI  - Application of the Ibis-T5000 pan-Orthopoxvirus assay to quantitatively detect
      monkeypox viral loads in clinical specimens from macaques experimentally infected
      with aerosolized monkeypox virus.
AB  - Monkeypox virus (MPXV), a member of the family Poxviridae and genus
      Orthopoxvirus, causes a smallpox-like disease in humans. A previously described
      pan-Orthopoxvirus assay, based on a broad-range polymerase chain reaction (PCR)
      coupled with electrospray ionization mass spectrometry (PCR/ESI-MS), was
      evaluated for its ability to detect MPXV from spiked human and aerosol-infected
      cynomolgous macaque (Macaca fascicularis) samples. Detection of MPXV DNA from
      macaque tissue, blood, and spiked human blood by the PCR/ESI-MS pan-Orthopoxvirus
      assay was comparable, albeit at slightly higher levels, to the current gold
      standard method of real-time PCR with the pan-Orthopoxvirus assay and had a limit
      of detection of 200 plaque-forming units. Furthermore, the platform was able to
      distinguish MPXV and vaccinia viruses that were spiked into macaque blood samples
      at various concentrations. This platform provides a new tool for the diagnosis
      and monitoring of orthopoxviral loads during vaccine or antiviral studies, but
      also could provide rapid identification during natural outbreaks or bioterrorism
      attacks.

PMID- 20134012
TI  - Association between nutritional status and severity of dengue infection in
      children in El Salvador.
AB  - Clinical observations and some studies suggest that dengue virus infection is
      more severe among children with better nutritional status. We examined the
      nutritional status of children in El Salvador and its relationship between this
      and the severity of dengue infection. Z-scores for weight-for-age, height-for
      age, and body mass index (BMI)-for-age of children with dengue fever (66), dengue
      hemorrhagic fever (62), and healthy controls (74) were compared. There were no
      differences in weight-for-age or BMI-for-age Z-scores between the three groups.
      Children with dengue fever had a greater height-for-age than healthy controls but
      no significant differences in rates of stunting. There was no difference in
      height between children with dengue fever and dengue hemorrhagic fever. Excess
      nutrition does not appear to be a risk factor for severe forms of dengue
      infection in El Salvador, nor does malnutrition appear to be predictive of good
      outcomes.

PMID- 20134013
TI  - The incidence, characteristics, and presentation of dengue virus infections
      during infancy.
AB  - Infants are a vulnerable and unique population at risk for dengue in endemic
      areas. This report describes the incidence and presenting clinical features of
      infant dengue virus (DENV) infections from a prospective community-based study
      performed between January 2007 and May 2009 in the Philippines. DENV3 was the
      predominant infecting serotype over a wide spectrum of disease severity, ranging
      from inapparent infection to dengue hemorrhagic fever (DHF). In 2007, the
      incidence of inapparent DENV infections during infancy was 103 per 1,000 persons
      person-years and 6-fold higher than symptomatic dengue. The age-specific
      incidence of infant DHF was 0.5 per 1,000 persons over the age of 3-8 months, and
      it disappeared by age 9 months. A febrile seizure, macular rash, petechiae, and
      lower platelet count were presenting clinical features associated with DENV
      infection among infants with acute undifferentiated febrile illnesses. Community
      based studies can help to delineate the incidence rates, disease spectrum, and
      clinical features of DENV infections during infancy.

PMID- 20134014
TI  - Avian communal roosts as amplification foci for West Nile virus in urban areas in
      northeastern United States.
AB  - West Nile virus (WNV) perpetuates in an enzootic transmission cycle involving
      Culex mosquitoes and virus-competent avian hosts. In the northeastern United
      States, the enzootic vectors, Cx. pipiens and Cx. restuans, feed preferentially
      on American robins (Turdus migratorius), suggesting a key role for this bird
      species in the WNV transmission cycle. We examined the role of American robin
      communal roosts as virus amplification foci in greater New Haven, Connecticut.
      Robin communal roosts were located by radio tracking. After mid-August, when most
      robins were using the roosts, Cx. pipiens and Cx. restuans fed often on robins
      and were significantly more infected with WNV at communal roosts than at non
      roosting sites. We also identified 6.4% human-derived blood meals in Aedes vexans
      in communal roosts. Our results indicate that communal roosts act as late-season
      amplification foci facilitating transmission to humans because of high infection
      rates, high abundance, and feeding patterns of enzootic and bridge vectors.

PMID- 20134015
TI  - Hospital-based surveillance for Japanese encephalitis at four sites in
      Bangladesh, 2003-2005.
AB  - We investigated the epidemiology and etiology of encephalitis at four tertiary
      hospitals in Bangladesh during 2003-2005. Patients who met a clinical case
      definition for acute encephalitis and had cerebrospinal fluid (CSF) pleocytosis
      were eligible for enrollment; a standardized sampling pattern was used to enroll
      eligible patients. Recent Japanese encephalitis virus (JEV) infection was defined
      by presence of IgM antibodies against JEV in CSF or serum. Twenty (4%) of 492
      cases had laboratory evidence of recent JEV infection; two died. All JE cases
      occurred during May-December, and cases were identified among all age groups. All
      cases resided in rural areas. Fifteen patients were re-assessed 4-6 weeks after
      hospitalization; 5 (33%) patients had physical disabilities and 7 (47%) reported
      cognitive difficulties. Infection with JEV is clearly an etiology of encephalitis
      in Bangladesh. Population-based studies to quantify burden of disease could
      assess options for targeted immunization programs.

PMID- 20134016
TI  - Experimental infections of Oryzomys couesi with sympatric arboviruses from
      Mexico.
AB  - Coues rice rat (Oryzomys couesi), a species abundant throughout Central America,
      was evaluated experimentally for the ability to serve as an amplifying host for
      three arboviruses: Patois (Bunyaviridae, Orthobunyavirus), Nepuyo
      (Orthobunyavirus), and Venezuelan equine encephalitis virus subtype ID
      (Togaviridae, Alphavirus). These three viruses have similar ecologies and are
      known to co-circulate in nature. Animals from all three cohorts survived
      infection and developed viremia with no apparent signs of illness and long
      lasting antibodies. Thus, O. couesi may play a role in the general maintenance of
      these viruses in nature.

PMID- 20134017
TI  - Transmission potential of two chimeric western equine encephalitis vaccine
      candidates in Culex tarsalis.
AB  - Western equine encephalitis virus (WEEV) is a zoonotic alphavirus that circulates
      in western North America between passerine birds and mosquitoes, primarily Culex
      tarsalis. Since it was isolated in 1930, WEEV has caused tens of thousands of
      equine deaths in addition to thousands of human cases. In addition because WEEV
      is a virus of agricultural importance in addition to a public health threat, we
      developed two live-attenuated chimeric vaccine candidates that have been shown to
      be immunogenic and efficacious in mouse models. Vaccine candidate strains were
      developed by inserting the structural protein genes of WEEV strain McMillan (McM)
      or CO92-1356 into a Sindbis virus (SINV) strain AR339 backbone. The SIN/McM
      chimera also derived the N-terminal half of its capsid gene from a North American
      eastern equine encephalitis virus (EEEV) strain FL39-939 (henceforth referred to
      as SIN/EEE/McM). Although these vaccines do not generate viremia in mice, we
      further assessed their safety by exposing Cx. tarsalis to artificial blood meals
      containing high viral titers of each vaccine candidate. Both viruses exhibited a
      decreased rate of infection, dissemination, and transmission potential compared
      with the parental alphaviruses. Specifically, SIN/CO92 infected 37% of mosquitoes
      and disseminated in 8%, but failed to reach the saliva of the mosquitoes. In
      contrast, the SIN/EEE/McM virus was unable to infect, disseminate, or be
      transmitted in the saliva of any mosquitoes. These findings suggest that both
      vaccine candidates are less competent than the parental strains to be transmitted
      by the primary mosquito vector, Cx. tarsalis, and are unlikely to be reintroduced
      into a natural WEEV transmission cycle.

PMID- 20134018
TI  - Continuous surveys and quality management in low-income countries: a good idea.

PMID- 20134023
TI  - Physiology . . . IUPS . . . wearing multiple hats.

PMID- 20134024
TI  - Phagocytosis of retinal rod and cone photoreceptors.
AB  - Photoreceptor cells maintain a roughly constant length by continuously generating
      new outer segments from their base while simultaneously releasing mature outer
      segments engulfed by the retinal pigment epithelium (RPE). Thus postmitotic RPE
      cells phagocytose an immense amount of material over a lifetime, disposing of
      photoreceptor cell waste while retaining useful content. This review focuses on
      current knowledge of outer segment phagocytosis, discussing the steps involved
      along with their critical participants as well as how various perturbations in
      outer segment (OS) disposal can lead to retinopathies.

PMID- 20134025
TI  - Rho signaling and tight junction functions.
AB  - Tight junctions are heteromeric protein complexes that act as signaling centers
      by mediating the bidirectional transmission of information between the
      environment and the cell interior to control paracellular permeability and
      differentiation. Insight into tight junction-associated signaling mechanisms is
      of fundamental importance for our understanding of the physiology of epithelia
      and endothelia in health and disease.

PMID- 20134026
TI  - Voltage-gated proton channels find their dream job managing the respiratory burst
      in phagocytes.
AB  - The voltage-gated proton channel bears surprising resemblance to the voltage
      sensing domain (S1-S4) of other voltage-gated ion channels but is a dimer with
      two conduction pathways. The proton channel seems designed for efficient proton
      extrusion from cells. In phagocytes, it facilitates the production of reactive
      oxygen species by NADPH oxidase.

PMID- 20134027
TI  - Regulation of ionotropic glutamate receptors by their auxiliary subunits.
AB  - Glutamate receptors are major excitatory receptors in the brain. Recent findings
      have established auxiliary subunits of glutamate receptors as critical modulators
      of synaptic transmission, synaptic plasticity, and neurological disorder. The
      elucidation of the molecular rules governing glutamate receptors and subunits
      will improve our understanding of synapses and of neural-circuit regulation in
      the brain.

PMID- 20134028
TI  - Stretch-activated ion channels: what are they?
AB  - Mechanosensitive ion channels (MSCs) exist in all cells, but mechanosensitivity
      is a phenotype not a genotype. Specialized mechanoreceptors such as the hair
      cells of the cochlea require elaborate mechanical impedance matching to couple
      the channels to the external stress. In contrast, MSCs in nonspecialized cells
      appear activated by stress in the bilayer local to the channel--within about
      three lipids. Local mechanical stress can be produced by far-field tension,
      amphipaths, phase separations, the cytoskeleton, the extracellular matrix, and
      the adhesion energy between the membrane and a patch pipette. Understanding MSC
      function requires under standing the stimulus.

PMID- 20134029
TI  - Prediction of human functional genetic networks from heterogeneous data using RVM
      based ensemble learning.
AB  - MOTIVATION: Three major problems confront the construction of a human genetic
      network from heterogeneous genomics data using kernel-based approaches:
      definition of a robust gold-standard negative set, large-scale learning and
      massive missing data values. RESULTS: The proposed graph-based approach generates
      a robust GSN for the training process of genetic network construction. The RVM
      based ensemble model that combines AdaBoost and reduced-feature yields improved
      performance on large-scale learning problems with massive missing values in
      comparison to Naive Bayes. CONTACT: dargenio@bmsr.usc.edu SUPPLEMENTARY
      INFORMATION: Supplementary material is available at Bioinformatics online.

PMID- 20134030
TI  - Non-linear classification for on-the-fly fractional mass filtering and targeted
      precursor fragmentation in mass spectrometry experiments.
AB  - MOTIVATION: Mass spectrometry (MS) has become the method of choice for
      protein/peptide sequence and modification analysis. The technology employs a two
      step approach: ionized peptide precursor masses are detected, selected for
      fragmentation, and the fragment mass spectra are collected for computational
      analysis. Current precursor selection schemes are based on data- or information
      dependent acquisition (DDA/IDA), where fragmentation mass candidates are selected
      by intensity and are subsequently included in a dynamic exclusion list to avoid
      constant refragmentation of highly abundant species. DDA/IDA methods do not
      exploit valuable information that is contained in the fractional mass of high
      accuracy precursor mass measurements delivered by current instrumentation.
      RESULTS: We extend previous contributions that suggest that fractional mass
      information allows targeted fragmentation of analytes of interest. We introduce a
      non-linear Random Forest classification and a discrete mapping approach, which
      can be trained to discriminate among arbitrary fractional mass patterns for an
      arbitrary number of classes of analytes. These methods can be used to increase
      fragmentation efficiency for specific subsets of analytes or to select suitable
      fragmentation technologies on-the-fly. We show that theoretical generalization
      error estimates transfer into practical application, and that their quality
      depends on the accuracy of prior distribution estimate of the analyte classes.
      The methods are applied to two real-world proteomics datasets. AVAILABILITY: All
      software used in this study is available from http://software.steenlab.org/fmf
      CONTACT: hanno.steen@childrens.harvard.edu SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 20134031
TI  - Statistical analysis of chronic obstructive pulmonary disease exacerbations in
      clinical studies: expectations and limitations.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (COPD) occur more
      frequently with increasing COPD severity and are associated with increased
      morbidity, reduced quality of life, and increased risk of mortality. The
      prevention and assessment of exacerbations, as a clinically and therapeutically
      relevant parameter, is a central aspect of clinical COPD studies. The aim of this
      review is to identify pitfalls in the analysis of the parameter of exacerbation
      and to describe the criteria that need to be considered in the statistical
      analysis of exacerbation studies.

PMID- 20134032
TI  - Sleep and breathing in idiopathic pulmonary fibrosis.
AB  - The outcome of patients with idiopathic pulmonary fibrosis (IPF), which
      represents the most common type of idiopathic pulmonary pneumonias, is poor.
      Breathlessness and coughing are usually progressive and about 50% of he patients
      die within 3 years after diagnosis. The effect of medical treatment in terms of
      survival is disappointing. Most of the currently available studies only focus on
      daytime diagnostics and therapy. The role of sleep quality and sleep disordered
      breathing in IPF is only investigated in a small number of papers, which can be
      summarized as follows: sleep fragmentation in IPF is very common. The reasons
      might be coughing, nocturnal oxygen desaturations, and increased respiratory
      drive. Sleep disorders in IPF have a profound impact on the quality of life.
      Oxygen desaturations often appear during sleep and can be predicted by the PaO(2)
      during wakefulness. There are no evidence-based recommendations concerning the
      indication for oxygen therapy and non-invasive ventilation during sleep in IPF.
      Obstructive sleep apnea (OSA) has no increased incidence with the exception of
      the IPF patients with an increased body mass index. If, however, OSA is present
      in IPF oxygen desaturations are more profound. The therapy of sleep disorders and
      sleep disordered breathing in IPF is individual. But in the absence of an
      effective treatment of IPF, optimization of sleep and life quality by the
      treatment of sleep disorders seems to be a primary goal. Further studies are
      needed to determine special sleep-related treatment effects.

PMID- 20134033
TI  - Treatment of systemic diseases by inhalation of biomolecule aerosols.
AB  - Clinical experience since many years has shown that aerosol inhalation is an
      established route for the treatment of pulmonary diseases. In contrast, treatment
      of systemic diseases by means of aerosol inhalation is a novel therapeutic
      approach. This was caused for a long time by a lack of accuracy, efficiency, and
      reproducibility of the administered drug doses due to a poor knowledge of the
      physiological background of aerosol inhalation, an insufficient inhaler
      technology as well as a suboptimal breathing procedure. However, these problems
      have been solved in the last years and nowadays modern aerosol delivery systems
      allow the production of an aerosol with a defined and optimised particle size
      combined with an optimized breathing maneuver and optimization of the efficacy of
      the technology. Clinical studies demonstrated that only a small number of
      morphological factors (e.g., exogen allergic alveolitis, active sarcoidosis,
      active smoking) influence alveolar drug deposition and the inhaled systematically
      active compounds caused no relevant allergic reactions even after inhalation for
      longer time periods. Up to now, most data are available for the inhalation of
      insulin which has been introduced in clinical treatment for a short time.
      However, a lot of other molecules have been tested in aerosol inhalation studies.
      This review describes some examples other than insulin in the field of inhalant
      treatment of systemic diseases.

PMID- 20134034
TI  - Association of oxidative stress and GST-T1 gene with childhood bronchial asthma.
AB  - There is increasing evidence that bronchial asthma is associated with increased
      oxidative stress. Reactive oxygen species are produced in each organism as by
      products of several essential reactions and can damage biomolecules. Asthma is a
      complex chronic inflammatory disorder of the airways, with many candidate genes
      suspected as being important in its development. Glutathione S-transferase (GST)
      is such a gene due to its role in protection against oxidative stress. In the
      present study, we examined the hypothesis that increased oxidative stress and
      polymorphism in the GST-T1 gene are associated with childhood asthma. We found
      that the amount of sulfhydryl groups significantly decreased and the content of
      thiobarbituric acid-reactive substances increased in the group of asthmatic
      children, compared with healthy controls. The GST-T1 null genotype was more
      frequent among the asthma patients. These results suggest that the GST-T1 null
      genotype and increased oxidative stress may play a role in the asthma
      pathogenesis in children.

PMID- 20134035
TI  - Expression of superoxide dismutase and matrix metalloproteinase type 2 in
      diaphragm muscles of young rats.
AB  - Moderate physical activity increases antioxidant defenses, whereas intensive
      activity is associated with oxidative stress. In this study we investigated the
      expression of superoxide dismutase (Cu,Zn-SOD), a major antioxidant defense
      enzyme, and that of the proteolytic enzyme matrix metalloproteinase-2 (MMP-2) in
      exercising muscle tissue. Treadmill running was used as a model to investigate
      the mechanism involved in muscle use and over use. Sprague-Dawley female rats (4
      months old) were randomly assigned to 3 groups: running group I, trained at a
      slow speed (18 m/min; approximately 50% VO(2)), running group II, trained at a
      very fast speed (32 m/min; approximately 75% VO(2)), for 3 weeks, and group III -
      control, non-running group. Cu,Zn-SOD was measured spectrophotometrically at 320
      nm by assessing the inhibition of cytochrome c reduction by xanthine oxidase. MMP
      2 levels of protein and mRNA were assessed in the diaphragm by Western blotting
      and by reverse transcriptase-polymerase chain reaction, respectively. We found
      that Cu,Zn-SOD level significantly decreased in the crural diaphragm muscle of
      rats three weeks after fast speed running, whereas it remained unchanged in the
      sternal diaphragm muscle three weeks after slow speed running. The expression of
      MMP-2 increased in both fast and slow running groups; however, it was
      particularly prominent in the fast twitch muscle fibers type IIb. We conclude
      that the crural diaphragm muscle, which contains significantly more type IIb
      fibers, was more affected following fast speed running than the sternal/costal
      diaphragm muscles, which have an equal distribution of slow twitch (type I) and
      fast twitch (type IIb) muscle fibers.

PMID- 20134036
TI  - Kinetics of calcium ion concentration accompanying transduction of signals into
      neutrophils from diabetic patients and its modification by insulin.
AB  - The goal of the study was to evaluate the process of Ca(2+)-mediated transduction
      of signals into neutrophils from patients with type I diabetes and its
      modification by insulin. The study was performed with the use of isolated
      peripheral blood neutrophils from 20 diabetic patients and 30 healthy volunteers.
      Isolated granulocytes were stimulated separately by fMLP or insulin, or by both
      substances added to the medium in combinations: fMLP + insulin (after 20 min) or
      insulin + fMLP (after 20 min). fMLP evoked fast intracellular increase of free
      Ca(2+) concentration in neutrophils compared with the resting state (P<0.001).
      Similarly, the peak of fluorescence, as measured by Fluo 3 to Fura Red ratio, was
      significantly higher in neutrophils stimulated by insulin. Insulin did not cause
      any changes in intracellular Ca(2+) level when it was added to the previously
      fMLP-stimulated cells. Prestimulation with insulin significantly decreased fMLP
      induced intracellular free Ca(2+) concentration, expressed as Fluo3/Fura Red
      ratio compared with fMLP alone (1.77 +/- 0.6 vs. 2.63 +/- 0.8, P<0.001). No
      relation between initial intracellular Ca(2+) in the resting state and the
      response to insulin was found. Nor was the response to fMLP alone related to
      intracellular Ca(2+) before stimulation. A strong correlation was observed
      between initial intracellular Ca(2+) after incubation with insulin and the
      response to fMLP (r=0.90, P<0.0001). In diabetic granulocytes, the intracellular
      Ca(2+) was significantly lower than in those from healthy donors in unstimulated
      cells (P<0.001), after fMLP stimulation (P<0.0001), in medium enriched by insulin
      (P<0.05), and after fMLP stimulation in insulin rich medium (P<0.001). Only in
      fMLP prestimulated samples, the emission of light did not differ after
      stimulation with insulin in granulocytes from both diabetic and healthy subjects.
      In conclusion, patients with type I diabetes have decreased levels of cytosolic
      Ca(2+) after insulin and fMLP stimulation in polymorphonuclear granulocytes. This
      abnormality is probably primarily responsible for the impaired neutrophilic
      function seen in these patients.

PMID- 20134037
TI  - Aging and expression of heme oxygenase-1 and endothelin-1 in the rat carotid body
      after chronic hypoxia.
AB  - Hypoxia transiently increases transcription of the gene encoding heme oxygenase-1
      (HO-1) and potently activates production of endothelin-1 (ET-1), the latter of
      which plays a central role in cellular adaptation to hypoxia. The ventilatory
      response to hypoxia attenuates with aging, and decreased responsiveness to
      hypoxia is seen in the aged vs. young rats, suggesting that the functionality of
      the oxygen-sensitive mechanism is age-dependent. In the present study, we
      examined the effects of aging on the expression of HO-1 and ET-1 in the carotid
      body, which is a small cluster of chemoreceptors and supporting cells that
      measure changes in the composition of arterial blood flowing through it. Our
      results revealed that HO-1 and ET-1 were expressed in carotid bodies of both
      young and old rats, although less so in the old ones. Exposure to chronic
      intermittent hypoxia significantly increased both HO-1 and ET-1 immunoreactivity
      in both young and old carotid body tissues, with the persisting age-dependent
      inequality to the disadvantage of old age. Considering that ET-1 is capable of
      enhancing intermittent hypoxia-induced chemosensory responses by the carotid
      body, our results suggest that decreased induction of ET-1 and HO-1 during aging
      could form the basis for age-related reductions in chemosensory discharge.

PMID- 20134038
TI  - Feasibility of the Epworth Sleepiness Scale in a sample of geriatric in-hospital
      patients.
AB  - Excessive daytime sleepiness (EDS) is a major health concern in geriatric
      patients. EDS affects quality of life, daytime function, and mortality. The
      Epworth Sleepiness Scale (ESS) is a standard tool for the assessment daytime
      sleepiness, but the feasibility of the ESS has never been investigated in elderly
      subjects. We applied the ESS to a random sample of geriatric in-hospital
      patients. The aim of the study was to reveal the frequency and the risk factors
      for processing failure of the ESS in geriatric patients. 458 patients with a mean
      age of 82+/-8 years were included. One hundred sixty six (36%) completed the ESS,
      118 (28%) patients had omissions of items, and 174 (38%) patients were unable to
      respond to any item. Completion of the ESS correlated significantly with age,
      disability, dementia, impairment of vision, and hearing. Omitted items were
      related to mobility and activities outside the house. Logistic regression
      analysis with completed ESS as a dependent variable revealed that dementia,
      disability, heart failure, and COPD were independent and significant risk factors
      for processing failure. The majority of patients of a geriatric unit are unable
      to complete the ESS. Since EDS is a frequent finding with a negative impact on
      health, the development of a reliable and valid tool for the assessment of EDS in
      elderly subjects is needed.

PMID- 20134039
TI  - Influence of type of treatment for sleep apnea on activities of daily living in a
      sample of elderly patients with severe sleep apnea.
AB  - Sleep disordered breathing (SDB) is a frequent finding in the elderly. SDB is
      related to morbidity, mortality, quality of life, disability, and cognitive
      impairment. Treatment of choice for SDB is nasal positive airway pressure
      breathing (nCPAP). The impact of treatment for SDB on activities of daily living
      (ADLs) is unclear. We therefore investigated the relationship between SDB and
      ADLs in a sample of elderly in-hospital patients with severe SDB defined as a
      oxygen desaturation index of 30 events per hour. All patients eligible were
      assigned to nCPAP therapy. Patients with refusal of nCPAP were offered nocturnal
      oxygen supply via nasal prongs. The Barthel-index (BI) at admission and discharge
      was used to measure ADLs. Two hundred patients with a mean age of 81+/-7 years
      were included. 22 (11%) patients accepted nCPAP therapy, 42 (21%) patients
      accepted oxygen therapy and 136 (68%) patients refused both treatment options.
      The subgroups did not differ significantly in BI at admission and length of stay
      in hospital. BI increased from 42+/-28 to 49+/-30 in patients with refusal of any
      treatment, from 39+/-23 to 61+/-20 in patients with oxygen therapy and from 48+/
      35 to 72+/-28 in patients with nCPAP therapy. The BI at discharge differed
      significantly between all three patients groups (p< 0.03). Logistic regression
      analysis revealed that Barthel Index at admission and treatment with nCPAP or
      treatment with oxygen were independently associated with a gain in BI of at least
      30 points. Age, dementia or length of in-hospital stay showed no association with
      gain in BI. This is the first study that shows an impact of treatment for severe
      SDB on ADLs in elderly patients. Furthermore, treatment with nCPAP and oxygen
      supply nearly had the same impact on ADLs. Since the higher rate of acceptance of
      oxygen therapy and the important impact of oxygen supply on BI, administration of
      oxygen seems to be a rational alternative in elderly subjects with severe sleep
      apnea and refusal of nCPAP.

PMID- 20134040
TI  - Leukotriene B4, 8-iso-prostaglandin F2 alpha, and pH in exhaled breath condensate
      from asymptomatic smokers.
AB  - Long-term cigarette smoking is the major etiological factor for the development
      of chronic obstructive pulmonary disease (COPD). Airway inflammation and
      oxidative stress are implicated in the pathogenesis. Biomarkers reflecting these
      responses could be analyzed in exhaled breath condensate (EBC). Recently, it
      became obvious that mediator concentrations in EBC could be influenced by age of
      the subjects, equipment, sampling properties, and the analytical assays applied.
      In the present study we evaluated 8 smokers (20-56 yr) and 16 non-smoking adults
      (18-60 yr) with normal spirometry and no episode of airway infection during 6
      weeks prior to the study. EBC samples were obtained with the commercial device
      ECoScreen2 at a controlled temperature of -20 degrees C. Leukotriene B(4)
      (LTB(4), marker of inflammation), 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2
      alpha)/8-isoprostane, oxidative stress) concentrations, and pH were measured.
      With 10 min of tidal breathing, a lower EBC volume was collected in smokers
      (median 1.22 ml; interquantil range 1.06-1.74 ml) than in non-smokers (1.6 ml;
      1.16-2.21 ml; P=0.06). Significant differences were found in pH in smokers
      compared with non-smokers (7.14 (5.70-7.43) vs. 7.59 (7.28-7.73); P<0.01). No
      significant differences were observed in EBC concentrations of LTB(4) or 8-iso
      PGF(2 alpha). The study demonstrates that acidopnea is detectable in otherwise
      asymptomatic smokers and might precede changes in the level of arachidonic acid
      metabolites. For pH is considered to be the most validated marker determined in
      EBC samples, it may be useful for screening asymptomatic individuals for smoking
      induced early airway damage.

PMID- 20134041
TI  - Cough reflex sensitivity in various phenotypes of childhood asthma.
AB  - Cough is a major symptom in some children with asthma, but the relationship
      between cough and the severity of asthma is defined insufficiently. As cough
      represents common problem of pediatrics, several objective methods for its
      assessment were developed. Cough reflex sensitivity (CRS) test with capsaicin is
      one of the most important tools for studying cough. In the present study, we
      aimed to study the CRS in various phenotypes of childhood asthma. We found that,
      in general, CRS was increased in asthmatic children compared with controls. The
      most evident increase of CRS was observed during acute asthma exacerbation, in
      children suffering from asthma with concomitant allergic rhinitis, and in atopic
      asthmatics. Interestingly, we noted a significant decline in lung function after
      capsaicin CRS. Various laboratory and clinical characteristics of asthmatic
      children influence cough sensitivity to a different extent. Cough reflex
      sensitivity measurement can add valuable information beside the commonly used
      spirometric and inflammometric methods in the management of asthmatic children.

PMID- 20134042
TI  - Spirometry in preschool children: time has come for new reference values.
AB  - Lung function measurements play an essential role in early diagnosis and
      monitoring of bronchial asthma in children. For clinical evaluation, measurements
      are commonly compared to reference values. However, these reference values are
      calculated based on measurements performed in groups of mostly older children and
      young adults two or three decades ago. In the present, cross-sectional study,
      lung function measurements were performed in 518 children (241 boys and 277
      girls; mean age 6.0+/-0.3 years) at a regular medical check prior to school
      enrollment. Spirometry was done using the MasterScreen IOS (Cardinal Health,
      Wurzburg). We recorded forced vital capacity (FVC), forced expiratory volume in
      one second (FEV(1)), maximal expiratory flow (PEF), and maximal expiratory flow
      at 75, 50, and 25% of vital capacity (MEF(75), MEF(50), MEF(25)). We found that
      FEV(1) and FVC corresponded to reference values (101.0+/-14.9% and 95.4+/-13.6%,
      in boys and girls, respectively). In maneuvers satisfying ATS/ERS criteria (T(E)
      >1 sec), forced expiratory (parameters (PEF, MEF(50)) reached only 68.9+/-13.6
      and 75.9+/-26.6% of reference values, in boys and girls, respectively). There was
      no significant correlation of lung function parameters to BMI. In conclusion, the
      hitherto reference values largely overestimate the maximal flow rates of
      preschool children performing a forced spirometry with T(E) >1 sec. At the age of
      6, forced expiratory flow values are not (yet) impaired by an increased BMI.
      Standardized spirometry starting in preschool children allows closely evaluating
      the individual development of lung function during follow-up measurements.

PMID- 20134043
TI  - Relationship between airway wall thickness assessed by high-resolution computed
      tomography and lung function in patients with asthma and chronic obstructive
      pulmonary disease.
AB  - Airway remodeling in asthma and chronic obstructive pulmonary disease (COPD)
      results in thickening of bronchial walls and may affect lung function. In the
      present study we set out to evaluate the relationship between small airway wall
      thickness and the lung function parameters in patients with asthma and COPD. The
      study was performed in 10 patients with asthma (4M/6F, the mean age 37+/-13 yr)
      and 12 patients with COPD (7M/5F, the mean age 57+/-9 yr) with stable, mild to
      moderate disease. The study group characteristics were based on clinical
      assessment and lung function testing (spirometry, body plethysmography,
      methacholine challenge test). All patients underwent chest high resolution
      computerized tomography with small bronchi (external diameter 1-5 mm) cross
      section measurements at five selected lung levels. The following parameters were
      measured in end-inspiratory scans: external (D) and internal (L) diameters, wall
      area (WA), percentage of the wall area (WA%), wall thickness (WT), and WT/D ratio
      (BWT). We found no significant correlations between airway wall thickness and
      spirometric parameters in either group. In the asthma group, the relationships
      between WA% and BWT, on the one side, and postbronchodilator residual volume, on
      the other, were noted (r=0.72; P<0.05 and r=0.72; P<0.05, respectively). In the
      COPD group, WA% related with airway resistance (r=0.72; P<0.05). The correlations
      between WA% and PC(20) (r=-0.61; P<0.05) and BWT and PC(20) (r=-0.72; P<0.05)
      were found in the COPD group. There was also a relationship between WA% and
      airway resistance (Raw) (r=0.72; P<0.05) and BWT and Raw (r=0.45; P=0.1). The
      number of pack-years correlated with WA and WT in COPD patients. In conclusion,
      the study shows that the thickening of airway wall in asthma is reflected by an
      increase in the indices of air trapping and in COPD this thickening results in a
      higher airway resistance and responsiveness. In COPD, the thickening of airway
      wall also is related to exposure to tobacco smoke.

PMID- 20134044
TI  - Expression of CD152 (CTLA-4) in children with autoimmune thyroiditis and +49 A/G
      polymorphism of exon 1 of the CTLA-4 gene.
AB  - CTLA-4 gene is one of the strongest locus of genetic susceptibility to autoimmune
      thyroid diseases. The aim of the present study was to investigate surface
      expression of CTLA-4 on peripheral T cells in homozygotes AA and GG at position
      +49 of CTLA-4 gene in children with Hashimoto's thyroiditis and in healthy
      controls. Blood samples were obtained from 100 children: 45 with Hashimoto's
      thyroiditis and 55 controls. CTLA-4 exon 1 polymorphism was defined by SSCP and
      RFLP with BbvI enzyme. T cells were analyzed with three color flow cytometry by
      Coulter EPICS XL. We found that CTLA-4 expression was significantly lower in the
      thyroiditis patients than in controls, but CTLA-4 expression in homozygotes GG
      and AA was comparable. We therefore conclude that decreased expression of CTLA-4
      on T cells in children with Hashimoto's thyroiditis is not dependent on
      polymorphic changes at position +49 of CTLA-4 gene.

PMID- 20134045
TI  - Increased pro-inflammatory activity and impairment of human monocyte
      differentiation induced by in vitro exposure to cigarette smoke.
AB  - Cigarette smoking (CS) is associated with a variety of human pathologies
      including cardiovascular disease and cancer. Human monocytes are prevalent in
      oral and respiratory mucosa and may be affected by exposure to CS, which induces
      oxidative stress. As a result, up-regulation of nuclear factor-kappaB (NF-kappaB)
      may occur. Our aims were to analyze a possible regulatory effect of CS on NF
      kappaB activity in human monocytes. Human monocyte cell lines were exposed to CS
      in vitro. Our findings show that in vitro exposure to CS did not affect viability
      of human monocytes and was associated with increased production and secretion of
      IL-8 and up-regulation of certain C-C chemokines. Inhibition of NF-kappaB with
      curcumin or parthenolide resulted in a decrease of IL-8 secretion. CS also
      impaired the differentiation of monocytes. However, induced secretion of IL-8
      from differentiated monocytes was not impaired. Our results indicate that
      exposure to CS stimulates pro-inflammatory activity of human monocytes through
      the activation of NF-kappaB pathway and also interferes with monocyte
      differentiation, which could play a role in the carcinogenic effects of cigarette
      smoking.

PMID- 20134046
TI  - Influence of xanthine derivatives on cough and airway reactivity in guinea pigs.
AB  - Xanthine derivatives may inhibit phosphodiesterases without selective action on
      their single isoforms. In this study, effects of theophylline and theobromine on
      cough and airway reactivity were evaluated in awake guinea pigs using double
      chamber whole body plethysmograph. Pre-treatment with theophylline and
      theobromine (10 mg/kg, i.p.) decreased the number of cough efforts evoked by
      inhalation of citric acid aerosol (0.6 mol/l) in both healthy and ovalbumin
      sensitized animals. Theophylline and theobromine decreased in vivo airway
      reactivity, i.e., specific airway resistance measured after nebulization of
      citric acid and histamine aerosol (10(-6) mol/l), only in ovalbumin-sensitized
      animals, whereas in vitro reactivity to cumulative doses of histamine and
      acetylcholine (10(8)-10(-3) mol/l) measured in organ chambers significantly
      decreased in both healthy and ovalbumin-sensitized animals, with more pronounced
      effect in the latter group. In conclusion, administration of theophylline and
      theobromine influenced the cough and airway reactivity in ovalbumin-sensitized
      guinea pigs, indicating the anti-inflammatory potential of xanthine derivatives.

PMID- 20134047
TI  - Influence of stimulation of nasal afferents on expiration reflex evoked from
      vocal folds.
AB  - Cough and sneezing are upregulated during the upper airway diseases, most likely
      to enhance airway defense. The aim of this study was to assess the expiration
      reflex (ER), another expulsive defensive airway reflex, during allergic rhinitis
      (AR) and intranasal (i.n.) capsaicin challenge. Thirty male guinea pigs,
      sensitized to ovalbumin were used in the study. They were divided into 3 groups
      of 10 animals each: AR group (i.n. ovalbumin), capsaicin group (i.n. capsaicin 50
      microM, 15 microl), and controls without any challenge. The animals were
      anesthetized with urethane (1.1 mg/kg) and allowed to breath spontaneously via
      tracheostomy. Metal canula was introduced into the right hemithorax to assess
      intrapleural pressure. ER was elicited by mechanical stimulation of the vocal
      folds using a thin nylon loop introduced upwards via tracheostomy. Maximal
      expiratory effort of ER (MEE) and the count of post-ER laryngeal coughs were
      evaluated. Mechanical stimulation of the vocal folds in controls produced
      isolated ER. They were followed by post-ER cough only in 11% of provocations. AR
      and capsaicin challenge increased MEE compared with that in controls (P<0.05). In
      these two groups of animals, the ER was followed by post ER-cough in 75% of
      provocations. The count of post-ER coughs in the group order control/AR/capsaicin
      was 0-2/2-4/1-3, respectively; P<0.05). The ER from the vocal folds is
      upregulated in a similar manner as is cough and sneeze. The central neuronal
      mechanisms are proposed to mediate this effect, but the spread of inflammation
      from upper airways to the larynx, verified histologically in the present study,
      may contribute as well.

PMID- 20134048
TI  - Provocation of aspiration reflexes and their effects on the pattern of cough and
      reflex apnea in cats.
AB  - Aspiration reflexes (AspRs) manifesting as reflex spasmodic inspirations and
      their effects on motor pattern of tracheobronchial cough and reflex apnea were
      studied on 22 spontaneously breathing pentobarbitone-anesthetized cats. AspRs
      induced during cough inspiration enhanced peak inspiratory (P<0.01) and
      expiratory (P<0.02) esophageal pressures, amplitudes of diaphragm (P<0.01) and
      abdominal muscles (P<0.05) EMG activity, and prolonged the entire expiratory
      period (P<0.01) and total cycle duration (P<0.05) of cough. Transient inhibitions
      and splits of cough expiration frequently occurred with AspR within active cough
      expiratory period; however, cough spatiotemporal characteristics were not altered
      significantly. Sub-threshold nasopharyngeal stimulation failing to provoke AspR
      had no significant effects on coughing. Hering-Breuer inflation apnea was
      moderately prolonged by AspRs (20%; P<0.05), unlike the apnea produced by
      continual mechanical laryngeal stimulation. AspRs are inducible during tested
      behaviors interacting with their motor pattern. Central mechanisms involving
      pulmonary stretch receptor stimulation is suggested for modulation of cough and
      inflation apnea by AspR.

PMID- 20134049
TI  - Excitability and rhythmicity of tracheobronchial cough is altered by aspiration
      reflex in cats.
AB  - Effects of nasopharyngeal stimulation on excitability and rhythmicity of
      mechanically induced tracheobronchial cough were examined on 18 pentobarbitone
      anesthetized cats. After the 17.2+/-2.4 aspiration reflexes (AspRs),
      tracheobronchial stimulation evoked lower number of coughs (P<0.05) with longer
      latency to the diaphragm activation (P<0.02), compared to control. AspRs induced
      within "inter-cough" periods (motor quiescence between individual coughs; 3.3
      AspRs per period) reduced cough number by 50% (P<0.01), shortened cough-related
      abdominal activity (P<0.02), prolonged inter-cough period (P<0.02), and the total
      cough cycle duration (P<0.05). Cough efforts occurred irregularly with very
      variable "inter-cough" distances and total cough cycle durations. The
      subthreshold nasopharyngeal stimulation (failing to evoke AspR) did not affect
      rhythmic coughing. AspRs induced during persisting post-stimulation coughs did
      not significantly reduce their number. Excitability and rhythmicity of
      mechanically induced tracheobronchial cough can be reduced by AspRs, but not by
      subthreshold nasopharyngeal stimulation. The suppressive effect of spasmodic
      inspirations on chronic cough is suggested.

PMID- 20134050
TI  - Effects of oxygen breathing on inspiratory muscle fatigue during resistive load
      in cycling men.
AB  - The aim of the present study was to determine the development of the inspiratory
      muscle fatigue in healthy human during incremental cycling to exhaustion under
      mild and heavy resistive loaded breathing in air and oxygen. Minute ventilation,
      tidal volume, respiratory rate, inspiratory mouth pressure, and parasternal EMG
      activities were recorded during an incremental cycling test under mild (12
      cmH(2)O x l(-1) x s(-1)) and heavy (40 cmH(2)O x l(-1) x s(-1)) resistive loading
      in air and oxygen in 8 men. The degree of inspiratory muscle fatigue was
      evaluated by analysis of the dynamics of inspiratory mouth pressure, 'tension
      time' index, and the fall of the high-to-low (H/L) ratio of the parasternal EMG.
      It was found that oxygen breathing slowed the development of inspiratory muscles
      fatigue evoked by incremental cycling only during mild resistive loading, whereas
      hyperoxia had not influence on inspiratory muscle endurance during heavy
      resistive loading.

PMID- 20134051
TI  - Evaluation of matrix metalloproteinases in serum of patients with amyotrophic
      lateral sclerosis with pattern recognition methods.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, which are
      present in central and peripheral nervous system. They are considered to be
      involved in the pathogenesis of several neurological diseases, as multiple
      sclerosis, Alzheimer disease, and amyotrophic lateral sclerosis (ALS). The aim of
      the present study was to evaluate the application of the pattern recognition
      methods for the assessment of MMPs in serum of patients with ALS. Thirty patients
      with amyotrophic lateral sclerosis (ALS), in two subgroups: (i) with mild and
      (ii) severe progressing ALS, and 15 control healthy subjects were studied. The
      metalloproteinases MT-MMP-1, MMP-2, MMP-9 were examined. Additional variables
      (age of subjects and disease duration) were also analyzed by using a standard,
      parallel and hierarchical classifiers. Our results indicate that: (i) MMP-2 in
      serum may be an important marker for the evaluation of ALS progress; (ii) the set
      of two features {MT-MMP-1, MMP-9} may be helpful in differentiation between ALS
      and healthy subjects; (iii) the error rates obtained for the pair-wise linear
      classifier were similar to those received for the classifiers (standard,
      parallel, and hierarchical) based on k-NN rule. We conclude that the pattern
      recognition methods may be useful for the evaluation of significance MMPs as
      markers in neurodegenerative diseases, such as ALS.

PMID- 20134052
TI  - Pulmonary surfactant: ultrastructural features and putative mechanisms of aging.
AB  - Pulmonary surfactant is essential for maintaining lung function. In the present
      study we attempted to gain insight into the mechanisms underlying changes in
      surfactant in old age. We examined the ultrastructure of surfactant-producing
      lamellar bodies of the alveolar epithelial cells and of extracellular tubular
      myelin unfolding from the lamellar bodies in the lungs of two contrasting age
      groups of rats: young, 2-3 months old and senescent, 26 months old. The study
      also focused on the plausible role of surfactant protein insufficiency in the
      process of surfactant aging. To this end, puromycin, a protein synthesis
      inhibitor, was used in vivo in young rats (12 mg/100 g body weight, i.p.) and its
      effects on surfactant ultrastructure were compared with the surfactant status in
      senescent rats. Lungs were rapidly dissected after being perfused with a mixture
      of aldehyde fixative and the tissue was subjected to the routine transmission
      electron microscopic procedures. Electronograms of the senescent lungs show that
      the alveolar epithelial lining layer and the lamellar bodies of type II cells,
      producing surfactant, displayed profound degenerative alterations. No regularly
      shaped myelin-tubular mesh, so characteristic of young lungs, could be recognized
      in the old ones. The aqueous, protein-containing hypophase of the alveolar
      epithelial lining, consisting of myelin tubules, no longer formed a solid layer
      integrated with the plasma membrane of type II cells. The effects of puromycin
      induced inhibition of protein synthesis on the alveolar lining layers in the
      young lungs were reminiscent of the picture seen in the untreated aged lungs. The
      similarity of surfactant changes after puromycin to those present in senescent
      lungs is suggestive of the possible role of decaying surfactant proteins in the
      natural process of surfactant aging. We conclude that protein deficiency possibly
      developing in old age may underlie surfactant degradation which may impact lung
      function in old age.

PMID- 20134053
TI  - Effects of cigarette smoke borne reactive nitrogen species on salivary alpha
      amylase activity and protein modifications.
AB  - Cigarette smoke (CS) is associated with a variety of human pathologies including
      cardiovascular disease and cancer. Oral squamous cell carcinoma (OSCC) is the
      most common malignancy of the head and neck. The major inducer of OSCC is
      exposure to tobacco. Recent studies demonstrated that oxidative and nitrosative
      stress contributes to the development of oral carcinogenesis through DNA damage.
      All salivary reactive nitrogen species (RNS) analyzed from OSCC patients are
      significantly higher in comparison with healthy subjects. Our findings show that
      CS and external RNS addition induced reduction in alpha-amylase activity and
      produced some excited carbonyl formation, but to a much less extant than CS. The
      addition of epigallocatechine-3-gallate (EGCG) to saliva produced no protective
      effect against damage to alpha-amylase activity. Our proposed mechanism for the
      decrease in alpha-amylase activity is the formation of adducts at SH groups of
      the alpha-amylase active site. In this case, EGCG was unable to counteract this
      phenomenon, as it does not reduce the concentration of disulfides, and does not
      alter the amount of protein-SH moieties. However, EGCG did reduce the levels of
      excited carbonyl formation. Our results indicate that although RNS are abundant
      in CS, a significant decrease in amylase activity is due to other components in
      CS, probably aldehydes, reacting with the thiol group of proteins by the Michael
      addition reaction.

PMID- 20134054
TI  - Towards the integration of computational systems biology and high-throughput
      data: supporting differential analysis of microarray gene expression data.
AB  - The paradigmatic shift occurred in biology that led first to high-throughput
      experimental techniques and later to computational systems biology must be
      applied also to the analysis paradigm of the relation between local models and
      data to obtain an effective prediction tool. In this work we introduce a unifying
      notational framework for systems biology models and high-throughput data in order
      to allow new integrations on the systemic scale like the use of in silico
      predictions to support the mining of gene expression datasets. Using the
      framework, we propose two applications concerning the use of system level models
      to support the differential analysis of microarray expression data. We tested the
      potentialities of the approach with a specific microarray experiment on the
      phosphate system in Saccharomyces cerevisiae and a computational model of the PHO
      pathway that supports the systems biology concepts.

PMID- 20134055
TI  - WebStruct and VisualStruct: Web interfaces and visualization for Structure
      software implemented in a cluster environment.
AB  - Structure, is a widely used software tool to investigate population genetic
      structure with multi-locus genotyping data. The software uses an iterative
      algorithm to group individuals into "K" clusters, representing possibly K
      genetically distinct subpopulations. The serial implementation of this programme
      is processor-intensive even with small datasets. We describe an implementation of
      the program within a parallel framework. Speedup was achieved by running
      different replicates and values of K on each node of the cluster. A web-based
      user-oriented GUI has been implemented in PHP, through which the user can specify
      input parameters for the programme. The number of processors to be used can be
      specified in the background command. A web-based visualization tool
      "Visualstruct", written in PHP (HTML and Java script embedded), allows for the
      graphical display of population clusters output from Structure, where each
      individual may be visualized as a line segment with K colors defining its
      possible genomic composition with respect to the K genetic sub-populations. The
      advantage over available programs is in the increased number of individuals that
      can be visualized. The analyses of real datasets indicate a speedup of up to
      four, when comparing the speed of execution on clusters of eight processors with
      the speed of execution on one desktop. The software package is freely available
      to interested users upon request.

PMID- 20134056
TI  - Conservation of the LexA repressor binding site in Deinococcus radiodurans.
AB  - The LexA protein is a transcriptional repressor of the bacterial SOS DNA repair
      system, which comprises a set of DNA repair and cellular survival genes that are
      induced in response to DNA damage. Its varied DNA binding motifs have been
      characterized and reported in the Escherichia coli, Bacillus subtilis, rhizobia
      family members, marine magnetotactic bacterium, Salmonella typhimurium and
      recently in Mycobacterium tuberculosis and this motifs information has been used
      in our theoretical analysis to detect its novel regulated genes in radio
      resistant Deinococcus radiodurans genome. This bacterium showed presence of SOS
      box like consensus sequence in the upstream sequences of 3166 genes with >60%
      motif score similarity percentage (MSSP) on both strands. Attempts to identify
      LexA-binding sites and the composition of the putative SOS regulon in D.
      radiodurans have been unsuccessful so far. To resolve the problem we performed
      theoretical analysis with modifications on reported data set of genes related to
      DNA repair (61 genes), stress response (145 genes) and some unusual predicted
      operons (21 clusters). Expression of some of the predicted SOS-box regulated
      operon members then was examined through the previously reported microarray data
      which confirm the expression of only single predicted operon i.e. DRB0143 (AAA
      superfamily NTPase related to 5-methylcytosine specific restriction enzyme
      subunit McrB) and DRB0144 (homolog of the McrC subunit of the McrBC restriction
      modification system). The methodology involved weight matrix construction through
      CONSENSUS algorithm using information of conserved upstream sequences of eight
      known genes including dinB, tagC, lexA, recA, uvrB, yneA of B. subtilis while
      lexA and recA of D. radiodurans through phylogenetic footprinting method and
      later detection of similar conserved SOS-box like LexA binding motifs through
      both RSAT & PoSSuMsearch programs. The resultant DNA consensus sequence had
      highly conserved 14 bp SOS-box like binding site.

PMID- 20134057
TI  - 2.5D visualisation of overlapping biological networks.
AB  - Biological data is often structured in the form of complex interconnected
      networks such as protein interaction and metabolic networks. In this paper, we
      investigate a new problem of visualising such overlapping biological networks.
      Two networks overlap if they share some nodes and edges. We present an approach
      for constructing visualisations of two overlapping networks, based on a
      restricted three dimensional representation. More specifically, we use three
      parallel two dimensional planes placed in three dimensions to represent
      overlapping networks: one for each network (the top and the bottom planes) and
      one for the overlapping part (in the middle plane). Our method aims to achieve
      both drawing aesthetics (or conventions) for each individual network, and
      highlighting the intersection part by them. Using three biological datasets, we
      evaluate our visualisation design with the aim to test whether overlapping
      networks can support the visual analysis of heterogeneous and yet interconnected
      networks.

PMID- 20134058
TI  - ReMatch: a web-based tool to construct, store and share stoichiometric metabolic
      models with carbon maps for metabolic flux analysis.
AB  - ReMatch is a web-based, user-friendly tool that constructs stoichiometric network
      models for metabolic flux analysis, integrating user-developed models into a
      database collected from several comprehensive metabolic data resources, including
      KEGG, MetaCyc and CheBI. Particularly, ReMatch augments the metabolic reactions
      of the model with carbon mappings to facilitate (13)C metabolic flux analysis.
      The construction of a network model consisting of biochemical reactions is the
      first step in most metabolic modelling tasks. This model construction can be a
      tedious task as the required information is usually scattered to many separate
      databases whose interoperability is suboptimal, due to the heterogeneous naming
      conventions of metabolites in different databases. Another, particularly severe
      data integration problem is faced in (13)C metabolic flux analysis, where the
      mappings of carbon atoms from substrates into products in the model are required.
      ReMatch has been developed to solve the above data integration problems. First,
      ReMatch matches the imported user-developed model against the internal ReMatch
      database while considering a comprehensive metabolite name thesaurus. This,
      together with wild card support, allows the user to specify the model quickly
      without having to look the names up manually. Second, ReMatch is able to augment
      reactions of the model with carbon mappings, obtained either from the internal
      database or given by the user with an easy-touse tool. The constructed models can
      be exported into 13C-FLUX and SBML file formats. Further, a stoichiometric matrix
      and visualizations of the network model can be generated. The constructed models
      of metabolic networks can be optionally made available to the other users of
      ReMatch. Thus, ReMatch provides a common repository for metabolic network models
      with carbon mappings for the needs of metabolic flux analysis community. ReMatch
      is freely available for academic use at
      http://www.cs.helsinki.fi/group/sysfys/software/rematch/.

PMID- 20134059
TI  - Widespread existence of uncorrelated probe intensities from within the same
      probeset on Affymetrix GeneChips.
AB  - We have developed a computational pipeline to analyse large surveys of Affymetrix
      GeneChips, for example NCBI's Gene Expression Omnibus. GEO samples data for many
      organisms, tissues and phenotypes. Because of this experimental diversity, any
      observed correlations between probe intensities can be associated either with
      biology that is robust, such as common co-expression, or with systematic biases
      associated with the GeneChip technology. Our bioinformatics pipeline integrates
      the mapping of probes to exons, quality control checks on each GeneChip which
      identifies flaws in hybridization quality, and the mining of correlations in
      intensities between groups of probes. The output from our pipeline has enabled us
      to identify systematic biases in GeneChip data. We are also able to use the
      pipeline as a discovery tool for biology. We have discovered that in the majority
      of cases, Affymetrix probesets on Human GeneChips do not measure one unique block
      of transcription. Instead we see numerous examples of outlier probes. Our study
      has also identified that in a number of probesets the mismatch probes are an
      informative diagnostic of expression, rather than providing a measure of
      background contamination. We report evidence for systematic biases in GeneChip
      technology associated with probe-probe interactions. We also see signatures
      associated with post-transcriptional processing of RNA, such as alternative
      polyadenylation.

PMID- 20134060
TI  - Data integration for spatio-temporal patterns of gene expression of zebrafish
      development: the GEMS database.
AB  - The Gene Expression Management System (GEMS) is a database system for patterns of
      gene expression. These patterns result from systematic whole-mount fluorescent in
      situ hybridization studies on zebrafish embryos. GEMS is an integrative platform
      that addresses one of the important challenges of developmental biology: how to
      integrate genetic data that underpin morphological changes during embryogenesis.
      Our motivation to build this system was by the need to be able to organize and
      compare multiple patterns of gene expression at tissue level. Integration with
      other developmental and biomolecular databases will further support our
      understanding of development. The GEMS operates in concert with a database
      containing a digital atlas of zebrafish embryo; this digital atlas of zebrafish
      development has been conceived prior to the expansion of the GEMS. The atlas
      contains 3D volume models of canonical stages of zebrafish development in which
      in each volume model element is annotated with an anatomical term. These terms
      are extracted from a formal anatomical ontology, i.e. the Developmental Anatomy
      Ontology of Zebrafish (DAOZ). In the GEMS, anatomical terms from this ontology
      together with terms from the Gene Ontology (GO) are also used to annotate
      patterns of gene expression and in this manner providing mechanisms for
      integration and retrieval. The annotations are the glue for integration of
      patterns of gene expression in GEMS as well as in other biomolecular databases.
      At the one hand, zebrafish anatomy terminology allows gene expression data within
      GEMS to be integrated with phenotypical data in the 3D atlas of zebrafish
      development. At the other hand, GO terms extend GEMS expression patterns
      integration to a wide range of bioinformatics resources.

PMID- 20134061
TI  - Integrative visual analysis of the effects of alternative splicing on protein
      domain interaction networks.
AB  - Proteins and their interactions are essential for the functioning of all
      organisms and for understanding biological processes. Alternative splicing is an
      important molecular mechanism for increasing the protein diversity in eukaryotic
      cells. Splicing events that alter the protein structure and the domain
      composition can be responsible for the regulation of protein interactions and the
      functional diversity of different tissues. Discovering the occurrence of splicing
      events and studying protein isoforms have become feasible using Affymetrix Exon
      Arrays. Therefore, we have developed the versatile Cytoscape plugin DomainGraph
      that allows for the visual analysis of protein domain interaction networks and
      their integration with exon expression data. Protein domains affected by
      alternative splicing are highlighted and splicing patterns can be compared.

PMID- 20134062
TI  - MoRAine--a web server for fast computational transcription factor binding motif
      re-annotation.
AB  - BACKGROUND: A precise experimental identification of transcription factor binding
      motifs (TFBMs), accurate to a single base pair, is time-consuming and diffcult.
      For several databases, TFBM annotations are extracted from the literature and
      stored 5' --> 3' relative to the target gene. Mixing the two possible
      orientations of a motif results in poor information content of subsequently
      computed position frequency matrices (PFMs) and sequence logos. Since these PFMs
      are used to predict further TFBMs, we address the question if the TFBMs
      underlying a PFM can be re-annotated automatically to improve both the
      information content of the PFM and subsequent classification performance.
      RESULTS: We present MoRAine, an algorithm that re-annotates transcription factor
      binding motifs. Each motif with experimental evidence underlying a PFM is
      compared against each other such motif. The goal is to re-annotate TFBMs by
      possibly switching their strands and shifting them a few positions in order to
      maximize the information content of the resulting adjusted PFM. We present two
      heuristic strategies to perform this optimization and subsequently show that
      MoRAine significantly improves the corresponding sequence logos. Furthermore, we
      justify the method by evaluating specificity, sensitivity, true positive, and
      false positive rates of PFM-based TFBM predictions for E. coli using the original
      database motifs and the MoRAine-adjusted motifs. The classification performance
      is considerably increased if MoRAine is used as a preprocessing step.
      CONCLUSIONS: MoRAine is integrated into a publicly available web server and can
      be used online or downloaded as a stand-alone version from
      http://moraine.cebitec. uni-bielefeld.de.

PMID- 20134063
TI  - A Bayes random field approach for integrative large-scale regulatory network
      analysis.
AB  - We present a Bayes-Random Fields framework which is capable of integrating
      unlimited data sources for discovering relevant network architecture of large
      scale networks. The random field potential function is designed to impose a
      cluster constraint, teamed with a full Bayesian approach for incorporating
      heterogenous data sets. The probabilistic nature of our framework facilitates
      robust analysis in order to minimize the influence of noise inherent in the data
      on the inferred structure in a seamless and coherent manner. This is later proved
      in its applications to both large-scale synthetic data sets and Saccharomyces
      Cerevisiae data sets. The analytical and experimental results reveal the varied
      characteristic of different types of data and refelct their discriminative
      ability in terms of identifying direct gene interactions.

PMID- 20134064
TI  - GOblet: annotation of anonymous sequence data with gene ontology and pathway
      terms.
AB  - The functional annotation of genomic data has become a major task for the ever
      growing number of sequencing projects. In order to address this challenge, we
      recently developed GOblet, a free web service for the annotation of anonymous
      sequences with Gene Ontology (GO) terms. However, to overcome limitations of the
      GO terminology, and to aid in understanding not only single components but as
      well systemic interactions between the individual components, we have now
      extended the GOblet web service to integrate also pathway annotations.
      Furthermore, we extended and upgraded the data analysis pipeline with improved
      summaries, and added term enrichment and clustering algorithms. Finally, we are
      now making GOblet available as a stand-alone application for high-throughput
      processing on local machines. The advantages of this frequently requested feature
      is that a) the user can avoid restrictions of our web service for uploading and
      processing large amounts of data, and that b) confidential data can be analysed
      without insecure transfer to a public web server. The stand-alone version of the
      web service has been implemented using platform independent Tcl-scripts, which
      can be run with just a single runtime file utilizing the Starkit technology. The
      GOblet web service and the stand-alone application are freely available at
      http://goblet.molgen.mpg.de.

PMID- 20134065
TI  - Effectiveness of closure of public places with time delay in disease control.
AB  - A theoretical basis for the evaluation of the effciency of quarantine measure is
      developed in a SIR model with time delay. In this model, the effectiveness of the
      closure of public places such as schools in disease control, modeled as a high
      degree node in a social network, is evaluated by considering the effect of the
      time delay in the identification of the infected. In the context of the SIR
      model, the relation between the number of infectious individuals who are
      identified with time delay and then quarantined and those who are not identified
      and continue spreading the virus are investigated numerically. The social network
      for the simulation is modeled by a scale free network. Closure measures are
      applied to those infected nodes with high degrees. The effectiveness of the
      measure can be controlled by the present value of the critical degree K(C): only
      those nodes with degree higher than K(C) will be quarantined. The cost C(Q)
      incurred for the closure measure is assumed to be proportional to the total links
      rendered inactive as a result of the measure, and generally decreases with K(C),
      while the medical cost C(Q) incurred for virus spreading increases with K(C). The
      total social cost (C(M) + C(Q)) will have a minimum at a critical K(*), which
      depends on the ratio of medical cost coeffcient alpha(M) and closure cost
      coeffcient alpha(Q). Our simulation results demonstrate a mathematical procedure
      to evaluate the effciency of quarantine measure. Although the numerical work is
      based on a scale free network, the procedure can be readily generalized and
      applied to a more realistic social network to determine the proper closure
      measure in future epidemics.

PMID- 20134066
TI  - Visual comparison of multiple gene expression datasets in a genomic context.
AB  - The need for novel methods of visualizing microarray data is growing. New
      perspectives are beneficial to finding patterns in expression data. The Bluejay
      genome browser provides an integrative way of visualizing gene expression
      datasets in a genomic context. We have now developed the functionality to display
      multiple microarray datasets simultaneously in Bluejay, in order to provide
      researchers with a comprehensive view of their datasets linked to a graphical
      representation of gene function. This will enable biologists to obtain valuable
      insights on expression patterns, by allowing them to analyze the expression
      values in relation to the gene locations as well as to compare expression
      profiles of related genomes or of different experiments for the same genome.

PMID- 20134067
TI  - An unusal distribution of 6-nt sequences near the transcription start site.
AB  - A new look at the transcription start is presented in which we can see
      transcription factors binding to both sides of the TSS as an essential
      requirement. Naturally the factor binding to the downstream region must be
      removed so that transcription process can continue. The presence of a number of
      distinct transcription factors also can be used to explain selective activation
      of various genes. The transcription start site by itself plays only a minor role
      in the whole process. We also suggest that mutations close to the TSS on the
      coding side can be fatal even if preserves the codon table.

PMID- 20134068
TI  - Converting biomolecular modelling data based on an XML representation.
AB  - Biomolecular modelling has provided computational simulation based methods for
      investigating biological processes from quantum chemical to cellular levels.
      Modelling such microscopic processes requires atomic description of a biological
      system and conducts in fine timesteps. Consequently the simulations are extremely
      computationally demanding. To tackle this limitation, different biomolecular
      models have to be integrated in order to achieve high-performance simulations.
      The integration of diverse biomolecular models needs to convert molecular data
      between different data representations of different models. This data conversion
      is often non-trivial, requires extensive human input and is inevitably error
      prone. In this paper we present an automated data conversion method for
      biomolecular simulations between molecular dynamics and quantum
      mechanics/molecular mechanics models. Our approach is developed around an XML
      data representation called BioSimML (Biomolecular Simulation Markup Language).
      BioSimML provides a domain specific data representation for biomolecular
      modelling which can effciently support data interoperability between different
      biomolecular simulation models and data formats.

PMID- 20134069
TI  - Graph-based sequence annotation using a data integration approach.
AB  - The automated annotation of data from high throughput sequencing and genomics
      experiments is a significant challenge for bioinformatics. Most current
      approaches rely on sequential pipelines of gene finding and gene function
      prediction methods that annotate a gene with information from different reference
      data sources. Each function prediction method contributes evidence supporting a
      functional assignment. Such approaches generally ignore the links between the
      information in the reference datasets. These links, however, are valuable for
      assessing the plausibility of a function assignment and can be used to evaluate
      the confidence in a prediction. We are working towards a novel annotation system
      that uses the network of information supporting the function assignment to enrich
      the annotation process for use by expert curators and predicting the function of
      previously unannotated genes. In this paper we describe our success in the first
      stages of this development. We present the data integration steps that are needed
      to create the core database of integrated reference databases (UniProt, PFAM,
      PDB, GO and the pathway database Ara-Cyc) which has been established in the ONDEX
      data integration system. We also present a comparison between different methods
      for integration of GO terms as part of the function assignment pipeline and
      discuss the consequences of this analysis for improving the accuracy of gene
      function annotation. The methods and algorithms presented in this publication are
      an integral part of the ONDEX system which is freely available from
      http://ondex.sf.net/.

PMID- 20134070
TI  - BioDWH: a data warehouse kit for life science data integration.
AB  - This paper presents a novel bioinformatics data warehouse software kit that
      integrates biological information from multiple public life science data sources
      into a local database management system. It stands out from other approaches by
      providing up-to-date integrated knowledge, platform and database independence as
      well as high usability and customization. This open source software can be used
      as a general infrastructure for integrative bioinformatics research and
      development. The advantages of the approach are realized by using a Java-based
      system architecture and object-relational mapping (ORM) technology. Finally, a
      practical application of the system is presented within the emerging area of
      medical bioinformatics to show the usefulness of the approach. The BioDWH data
      warehouse software is available for the scientific community at
      http://sourceforge.net/projects/biodwh/.

PMID- 20134071
TI  - Mining protein database using machine learning techniques.
AB  - With a large amount of information relating to proteins accumulating in databases
      widely available online, it is of interest to apply machine learning techniques
      that, by extracting underlying statistical regularities in the data, make
      predictions about the functional and evolutionary characteristics of unseen
      proteins. Such predictions can help in achieving a reduction in the space over
      which experiment designers need to search in order to improve our understanding
      of the biochemical properties. Previously it has been suggested that an
      integration of features computable by comparing a pair of proteins can be
      achieved by an artificial neural network, hence predicting the degree to which
      they may be evolutionary related and homologous. <br> We compiled two datasets of
      pairs of proteins, each pair being characterised by seven distinct features. We
      performed an exhaustive search through all possible combinations of features, for
      the problem of separating remote homologous from analogous pairs, we note that
      significant performance gain was obtained by the inclusion of sequence and
      structure information. We find that the use of a linear classifier was enough to
      discriminate a protein pair at the family level. However, at the superfamily
      level, to detect remote homologous pairs was a relatively harder problem. We find
      that the use of nonlinear classifiers achieve significantly higher accuracies.
      <br> In this paper, we compare three different pattern classification methods on
      two problems formulated as detecting evolutionary and functional relationships
      between pairs of proteins, and from extensive cross validation and feature
      selection based studies quantify the average limits and uncertainties with which
      such predictions may be made. Feature selection points to a ?"knowledge gap?" in
      currently available functional annotations. We demonstrate how the scheme may be
      employed in a framework to associate an individual protein with an existing
      family of evolutionarily related proteins.

PMID- 20134072
TI  - Discovering distinct patterns in gene expression profiles.
AB  - Traditional analysis of gene expression profiles use clustering to find groups of
      coexpressed genes which have similar expression patterns. However clustering is
      time consuming and could be diffcult for very large scale dataset. We proposed
      the idea of Discovering Distinct Patterns (DDP) in gene expression profiles.
      Since patterns showing by the gene expressions reveal their regulate mechanisms.
      It is significant to find all different patterns existing in the dataset when
      there is little prior knowledge. It is also a helpful start before taking on
      further analysis. We propose an algorithm for DDP by iteratively picking out
      pairs of gene expression patterns which have the largest dissimilarities. This
      method can also be used as preprocessing to initialize centers for clustering
      methods, like K-means. Experiments on both synthetic dataset and real gene
      expression datasets show our method is very effective in finding distinct
      patterns which have gene functional significance and is also effcient.

PMID- 20134073
TI  - Subgraph queries by context-free grammars.
AB  - We describe a method for querying vertex- and edge-labeled graphs using context
      free grammars to specify the class of interesting paths. We introduce a novel
      problem, finding the connection subgraph induced by the set of matching paths
      between given two vertices or two sets of vertices. Such a subgraph provides a
      concise summary of the relationship between the vertices. We also present novel
      algorithms for parsing subgraphs directly without enumerating all the individual
      paths. We evaluate experimentally the presented parsing algorithms on a set of
      real graphs derived from publicly available biomedical databases and on randomly
      generated graphs. The results indicate that parsing the connection subgraph
      directly is much more effective than parsing individual paths separately.
      Furthermore, we show that using a bidirectional parsing algorithm, in most cases,
      allows for searching twice as long paths as using a unidirectional search
      strategy.

PMID- 20134074
TI  - Goober: a fully integrated and user-friendly microarray data management and
      analysis solution for core labs and bench biologists.
AB  - Despite the large number of software tools developed to address different areas
      of microarray data analysis, very few offer an all-in-one solution with little
      learning curve. For microarray core labs, there are even fewer software packages
      available to help with their routine but critical tasks, such as data quality
      control (QC) and inventory management. We have developed a simple-to-use web
      portal to allow bench biologists to analyze and query complicated microarray data
      and related biological pathways without prior training. Both experiment-based and
      gene-based analysis can be easily performed, even for the first-time user,
      through the intuitive multi-layer design and interactive graphic links. While
      being friendly to inexperienced users, most parameters in Goober can be easily
      adjusted via drop-down menus to allow advanced users to tailor their needs and
      perform more complicated analysis. Moreover, we have integrated graphic pathway
      analysis into the website to help users examine microarray data within the
      relevant biological content. Goober also contains features that cover most of the
      common tasks in microarray core labs, such as real time array QC, data loading,
      array usage and inventory tracking. Overall, Goober is a complete microarray
      solution to help biologists instantly discover valuable information from a
      microarray experiment and enhance the quality and productivity of microarray core
      labs. The whole package is freely available at
      http://sourceforge.net/projects/goober. A demo web server is available at
      http://www.goober-array.org.

PMID- 20134075
TI  - An approach to pathway reconstruction using whole genome metabolic models and
      sensitive sequence searching.
AB  - Metabolic models have the potential to impact on genome annotation and on the
      interpretation of gene expression and other high throughput genome data. The
      genome of Streptomyces coelicolor genome has been sequenced and some 30% of the
      open reading frames (ORFs) lack any functional annotation. A recently constructed
      metabolic network model for S. coelicolor highlights biochemical functions which
      should exist to make the metabolic model complete and consistent. These include
      205 reactions for which no ORF is associated. Here we combine protein functional
      predictions for the unannotated open reading frames in the genome with ?'missing
      but expected?' functions inferred from the metabolic model. The approach allows
      function predictions to be evaluated in the context of the biochemical pathway
      reconstruction, and feed back iteratively into the metabolic model. We describe
      the approach and discuss a few illustrative examples.

PMID- 20134076
TI  - Global sequence properties for superfamily prediction: a machine learning
      approach.
AB  - Functional annotation of a protein sequence in the absence of experimental data
      or clear similarity to a sequence of known function is difficult. In this study,
      a simple set of sequence attributes based on physicochemical and predicted
      structural characteristics were used as input to machine learning methods. In
      order to improve performance through increasing the data available for training,
      a technique of sequence enrichment was explored. These methods were used to
      predict membership to 24 and 49 large and diverse protein superfamiles from the
      SCOP database. We found the best performance was obtained using an enriched
      training dataset. Accuracies of 66.3% and 55.6% were achieved on datasets
      comprising 24 and 49 superfamilies with LibSVM and AdaBoostM1 respectively. The
      methods used here confirm that domains within superfamilies share global sequence
      properties. We show machine learning models used to predict categories within the
      SCOP database can be significantly improved via a simple sequence enrichment
      step. These approaches can be used to complement profile methods for detecting
      distant relationships where function is difficult to infer.

PMID- 20134077
TI  - A new approach for modelling gene regulatory networks using fuzzy petri nets.
AB  - Gene Regulatory Networks are models of genes and gene interactions at the
      expression level. The advent of microarray technology has challenged computer
      scientists to develop better algorithms for modeling the underlying regulatory
      relationship in between the genes. Fuzzy system has an ability to search
      microarray datasets for activator/repressor regulatory relationship. In this
      paper, we present a fuzzy reasoning model based on the Fuzzy Petri Net. The model
      considers the regulatory triplets by means of predicting changes in expression
      level of the target based on input expression level. This method eliminates
      possible false predictions from the classical fuzzy model thereby allowing a
      wider search space for inferring regulatory relationship. Through formalization
      of fuzzy reasoning, we propose an approach to construct a rulebased reasoning
      system. The experimental results show the proposed approach is feasible and
      acceptable to predict changes in expression level of the target gene.

PMID- 20134078
TI  - Identifying the impact of G-quadruplexes on Affymetrix 3' arrays using cloud
      computing.
AB  - A tetramer quadruplex structure is formed by four parallel strands of DNA/ RNA
      containing runs of guanine. These quadruplexes are able to form because guanine
      can Hoogsteen hydrogen bond to other guanines, and a tetrad of guanines can form
      a stable arrangement. Recently we have discovered that probes on Affymetrix
      GeneChips that contain runs of guanine do not measure gene expression reliably.
      We associate this finding with the likelihood that quadruplexes are forming on
      the surface of GeneChips. In order to cope with the rapidly expanding size of
      GeneChip array datasets in the public domain, we are exploring the use of cloud
      computing to replicate our experiments on 3' arrays to look at the effect of the
      location of G-spots (runs of guanines). Cloud computing is a recently introduced
      high-performance solution that takes advantage of the computational
      infrastructure of large organisations such as Amazon and Google. We expect that
      cloud computing will become widely adopted because it enables bioinformaticians
      to avoid capital expenditure on expensive computing resources and to only pay a
      cloud computing provider for what is used. Moreover, as well as financial
      efficiency, cloud computing is an ecologically-friendly technology, it enables
      efficient data-sharing and we expect it to be faster for development purposes.
      Here we propose the advantageous use of cloud computing to perform a large data
      mining analysis of public domain 3' arrays.

PMID- 20134079
TI  - Integration of -omics data and networks for biomedical research with VANTED.
AB  - More and more often research focus in the fields of biology and medicine moves
      from the investigation of single phenomena to the analysis of complex cause and
      effect relations. The clarification of complicated relations requires the
      consideration of different domains, for instance, gene expression, protein, and
      metabolite data. Furthermore, it is often sensible not to analyze measured data
      in isolation, but to consider the context of relevant biological networks. In
      this paper newly developed functionalities of the VANTED system are presented.
      They allow users from medicine and biology to interactively structure extensive
      experiment data, to filter, to evaluate, and to visualize the data and the
      analysis results in context of biological networks and classification
      hierarchies.

PMID- 20134080
TI  - The LAILAPS search engine: relevance ranking in life science databases.
AB  - Search engines and retrieval systems are popular tools at a life science desktop.
      The manual inspection of hundreds of database entries, that reflect a life
      science concept or fact, is a time intensive daily work. Hereby, not the number
      of query results matters, but the relevance does. In this paper, we present the
      LAILAPS search engine for life science databases. The concept is to combine a
      novel feature model for relevance ranking, a machine learning approach to model
      user relevance profiles, ranking improvement by user feedback tracking and an
      intuitive and slim web user interface, that estimates relevance rank by tracking
      user interactions. Queries are formulated as simple keyword lists and will be
      expanded by synonyms. Supporting a flexible text index and a simple data import
      format, LAILAPS can easily be used both as search engine for comprehensive
      integrated life science databases and for small in-house project databases. With
      a set of features, extracted from each database hit in combination with user
      relevance preferences, a neural network predicts user specific relevance scores.
      Using expert knowledge as training data for a predefined neural network or using
      users own relevance training sets, a reliable relevance ranking of database hits
      has been implemented. In this paper, we present the LAILAPS system, the concepts,
      benchmarks and use cases. LAILAPS is public available for SWISSPROT data at
      http://lailaps.ipk-gatersleben.de.

PMID- 20134081
TI  - Scatter correction in digital mammography based on image deconvolution.
AB  - X-ray scatter is a major cause of nonlinearity in densitometry measurements using
      digital mammography. Previous scatter correction techniques have primarily used a
      single scatter point spread function to estimate x-ray scatter. In this study, a
      new algorithm to correct x-ray scatter based on image convolution was implemented
      using a spatially variant scatter point spread function which is energy and
      thickness dependent. The scatter kernel was characterized in terms of its
      scattering fraction (SF) and scatter radial extent (k) on uniform Lucite phantoms
      with thickness of 0.8-8.0 cm. The algorithm operates on a pixel-by-pixel basis by
      grouping pixels of similar thicknesses into a series of mask images that are
      individually deconvolved using Fourier image analysis with a distinct kernel for
      each image. The algorithm was evaluated with three Lucite step phantoms and one
      anthropomorphic breast phantom using a full-field digital mammography system at
      energies of 24, 28, 31 and 49 kVp. The true primary signal was measured with a
      multi-hole collimator. The effect on image quality was also evaluated. For all 16
      studies, the average mean percentage error in estimating the true primary signal
      was found to be -2.13% and the average rms percentage error was 2.60%. The image
      quality was seen to improve at every energy up to 25% at 49 kVp. The results
      indicate that a technique based on a spatially variant scatter point spread
      function can accurately estimate x-ray scatter.

PMID- 20134082
TI  - Toward acquiring comprehensive radiosurgery field commissioning data using the
      PRESAGE/optical-CT 3D dosimetry system.
AB  - Achieving accurate small field dosimetry is challenging. This study investigates
      the utility of a radiochromic plastic PRESAGE read with optical-CT for the
      acquisition of radiosurgery field commissioning data from a Novalis Tx system
      with a high-definition multileaf collimator (HDMLC). Total scatter factors (Sc,
      p), beam profiles, and penumbrae were measured for five different radiosurgery
      fields (5, 10, 20, 30 and 40 mm) using a commercially available optical-CT
      scanner (OCTOPUS, MGS Research). The percent depth dose (PDD), beam profile and
      penumbra of the 10 mm field were also measured using a higher resolution in-house
      prototype CCD-based scanner. Gafchromic EBT film was used for independent
      verification. Measurements of Sc, p made with PRESAGE and film agreed with mini
      ion chamber commissioning data to within 4% for every field (range 0.2-3.6% for
      PRESAGE, and 1.6-3.6% for EBT). PDD, beam profile and penumbra measurements made
      with the two PRESAGE/optical-CT systems and film showed good agreement with the
      high-resolution diode commissioning measurements with a competitive resolution
      (0.5 mm pixels). The in-house prototype optical-CT scanner allowed much finer
      resolution compared with previous applications of PRESAGE. The advantages of the
      PRESAGE system for small field dosimetry include 3D measurements, negligible
      volume averaging, directional insensitivity, an absence of beam perturbations,
      energy and dose rate independence.

PMID- 20134083
TI  - Real-time imaging for dose evaluation during antiproton irradiation.
AB  - Online monitoring of the stopping distribution of particle beams used for
      radiotherapy provides the possibility of detecting possible errors in dose
      deposition early during a given treatment session, and may therefore help to
      improve the quality of the therapy. Antiproton annihilation events produce
      several long-range secondary particles which can be detected in real time by
      standard high energy particle physics detector systems. In this note, Monte Carlo
      calculations are performed in order to study the feasibility of real-time imaging
      by detecting charged pions produced during antiproton irradiation of typical
      biological targets. A simple treatment plan in a water phantom is simulated and
      the results show that by detecting pi+/- the position and the size of the planned
      target volume can be located with precision in the order of 1 mm.

PMID- 20134084
TI  - Kernel density estimation-based real-time prediction for respiratory motion.
AB  - Effective delivery of adaptive radiotherapy requires locating the target with
      high precision in real time. System latency caused by data acquisition,
      streaming, processing and delivery control necessitates prediction. Prediction is
      particularly challenging for highly mobile targets such as thoracic and abdominal
      tumors undergoing respiration-induced motion. The complexity of the respiratory
      motion makes it difficult to build and justify explicit models. In this study, we
      honor the intrinsic uncertainties in respiratory motion and propose a statistical
      treatment of the prediction problem. Instead of asking for a deterministic
      covariate-response map and a unique estimate value for future target position, we
      aim to obtain a distribution of the future target position (response variable)
      conditioned on the observed historical sample values (covariate variable). The
      key idea is to estimate the joint probability distribution (pdf) of the covariate
      and response variables using an efficient kernel density estimation method. Then,
      the problem of identifying the distribution of the future target position reduces
      to identifying the section in the joint pdf based on the observed covariate.
      Subsequently, estimators are derived based on this estimated conditional
      distribution. This probabilistic perspective has some distinctive advantages over
      existing deterministic schemes: (1) it is compatible with potentially
      inconsistent training samples, i.e., when close covariate variables correspond to
      dramatically different response values; (2) it is not restricted by any prior
      structural assumption on the map between the covariate and the response; (3) the
      two-stage setup allows much freedom in choosing statistical estimates and
      provides a full nonparametric description of the uncertainty for the resulting
      estimate. We evaluated the prediction performance on ten patient RPM traces,
      using the root mean squared difference between the prediction and the observed
      value normalized by the standard deviation of the observed data as the error
      metric. Furthermore, we compared the proposed method with two benchmark methods:
      most recent sample and an adaptive linear filter. The kernel density estimation
      based prediction results demonstrate universally significant improvement over the
      alternatives and are especially valuable for long lookahead time, when the
      alternative methods fail to produce useful predictions.

PMID- 20134085
TI  - Single crystal targets may improve soft-tissue contrast in megavoltage imaging by
      means of coherent bremsstrahlung.
AB  - Coherent bremsstrahlung denotes the process of bremsstrahlung emission by
      electrons traversing a single crystal, causing prominent peaks in the resulting
      photon spectra at low energies. While this phenomenon has been known for decades,
      little attempt has been made to exploit its potential for megavoltage imaging,
      where the quality of images is affected by low contrast due to the lack of
      sufficient photons at the energy range suited for diagnostic purposes. We provide
      a theoretical foundation of coherent bremsstrahlung in the first-order Born
      approximation without confinement to high energies. Based on this theory, first
      evidence is given that diamond crystals are capable of boosting the amount of
      diagnostic photons by about 10-20%. It is shown that this behaviour is largely
      conserved for polychromatic electrons hitting thick targets, where multiple
      scattering dominates the energy distribution of the emitted photons.

PMID- 20134086
TI  - High-resolution tomography of positron emitters with clustered pinhole SPECT.
AB  - State-of-the-art small-animal single photon emission computed tomography (SPECT)
      enables sub-half-mm resolution imaging of radio-labelled molecules. Due to severe
      photon penetration through pinhole edges, current multi-pinhole SPECT is not
      suitable for high-resolution imaging of photons with high energies, such as the
      annihilation photons emitted by positron emitting tracers (511 keV). To deal with
      this edge penetration, we introduce here clustered multi-pinhole SPECT (CMP):
      each pinhole in a cluster has a narrow opening angle to reduce photon
      penetration. Using simulations, CMP is compared with (i) a collimator with
      traditional pinholes that is currently used for sub-half-mm imaging of SPECT
      isotopes (U-SPECT-II), and (ii), like (i) but with collimator thickness adapted
      to image high-energy photons (traditional multi-pinhole SPECT, TMP). At 511 keV,
      U-SPECT-II is able to resolve the 0.9 mm rods of an iteratively reconstructed
      Jaszczak-like capillary hot rod phantom, and while TMP only leads to small
      improvements, CMP can resolve rods as small as 0.7 mm. Using a digital tumour
      phantom, we show that CMP resolves many details not assessable with standard
      USPECT-II and TMP collimators. Furthermore, CMP makes it possible to visualize
      uptake of positron emitting tracers in sub-compartments of a digital mouse
      striatal brain phantom. This may open up unique possibilities for analysing
      processes such as those underlying the function of neurotransmitter systems.
      Additional potential of CMP may include (i) the imaging of other high-energy
      single-photon emitters (e.g. I-131) and (ii) localized imaging of positron
      emitting tracers simultaneously with single photon emitters, with an even better
      resolution than coincidence PET.

PMID- 20134087
TI  - Ethical guidelines for publication in Clinical Hemorheology and Microcirculation.

PMID- 20134088
TI  - Arsenic intoxication, a hemorheologic view.
AB  - Arsenic (As) is a toxic semi-metal of wide distribution in nature. People living
      in regions where drinking water contains large quantities of arsenic, have an
      unusually high likelihood of developing blood-vessel diseases, but little is
      known about the mechanisms involved, i.e. the blood rheologic alterations that
      would contribute to the circulatory obstruction. Erythrocytes are the main target
      cells for arsenic compounds systemically absorbed and their cell membrane is the
      first place against the toxic. In this paper we have examined the in vitro effect
      of arsenic (As(V)) on the rheologic properties of human erythrocytes in relation
      with membrane fluidity and internal microviscosity. According to our present
      results, As(V) treatment produces oxidative degradation of membrane lipids and
      alteration of internal microviscosity. These red blood cells (RBCs) membrane and
      cytoplasmic structural damage consequently alters RBCs rheologic properties: an
      alteration of the RBCs discoid shape to stomatocytes, a diminution of erythrocyte
      deformability and an enhancement of osmotic fragility and cell aggregability.
      These effects impaired blood fluid behaviour that contribute to obstruct
      peripheral circulation and provides anemia, both clinic evidences typical of
      arsenic cronic intoxication.

PMID- 20134089
TI  - B-flow and color Doppler sonography findings in iatrogenic carotid-jugular
      arteriovenous fistula.
AB  - We describe the case of a 66-year-old woman with an aortic valve reconstruction.
      Subsequently she presented with an arteriovenous fistula (AVF) between the left
      common carotid artery and internal jugular vein following several attempts of
      jugular catheter insertion. Due to aliasing, correct visualization of the fistula
      track was hindered by conventional color Doppler. However, by using the B-flow
      imaging technique, the fistula track could be detected without aliasing or
      overwriting. Duplex examination revealed an AVF between both vessels with an
      arterialized waveform in the left jugular vein and a high-velocity turbulent flow
      inside the fistula. Due to these findings we will change our routine scanning
      protocol for extracranial vessels and will use B-flow in indistinctive or
      difficult conditions to obtain additional informations.

PMID- 20134090
TI  - Inter-species hemorheologic differences in arterial and venous blood.
AB  - BACKGROUND: Hemorheologic factors such as red blood cell (RBC) aggregation and
      deformability differ according to species. In many comparative hemorheologic
      studies, only venous blood samples have been used for measurements. There is
      little published information comparing arterial and venous blood differences
      between species. We compared hemorheologic factors in arterial and venous blood
      in rats, dogs and humans. METHODS: Nineteen dogs and 12 rats were used. Human
      blood was obtained from 12 healthy volunteers. Blood gas analysis, hematocrit and
      elongation index which represents RBC deformability were measured in arterial and
      venous blood samples. The critical shear stress and aggregation index, both of
      which represent RBC aggregation, were also measured in arterial and venous blood.
      RESULTS: There were no arterial or venous differences in hematocrit, critical
      shear stress, or elongation index in dogs. In rats, RBC aggregation was not
      measurable. The hematocrit and elongation index of arterial blood were
      significantly lower than those of venous blood in rats. There were no arterial or
      venous differences in hematocrit, aggregation index, or elongation index in
      humans. CONCLUSION: Arterial and venous hemorheologic factors differed depending
      on the species. Further standardization is necessary for the measurement of
      hemorheologic variables.

PMID- 20134091
TI  - Plasma viscosity and mean platelet volume in patients undergoing coronary
      angiography.
AB  - BACKGROUND: Markers of platelet activation and haemorrheological indices have
      been demonstrated to play a role in the pathophysiology of atherosclerosis and
      cardiovascular events. In this study, we aimed at investigate the association
      between plasma viscosity and platelet indices in patients undergoing coronary
      angiography. MATERIALS AND METHODS: Three hundred and eighty four consecutive
      patients scheduled to undergo coronary angiography were included in the study.
      Prior to coronary angiography, blood samples were withdrawn to determine routine
      biochemical markers, blood cell analyses and viscosity measurements. According to
      the results of coronary angiography, patients were classified either in a
      subgroup with coronary artery disease (CAD; 1 or more stenoses >50%) or normal
      coronary arteries (NCA; no stenoses or <50%). RESULTS: There was a statistically
      significant correlation between plasma viscosity and mean platelet volume levels
      in all patients undergoing coronary angiography (r=0.199, p<0.001). Additionally,
      when correlation analysis was performed within each group, plasma viscosity
      significantly correlated with MPV both in patients with CAD (r=0.18, p=0.004) and
      in patients with NCAs (r=0.272, p=0.002). Linear regression analysis revealed
      that plasma viscosity was positively associated with MPV while platelet number
      was inversely but significantly associated with MPV. CONCLUSION: We have shown
      for the first time that MPV correlates with plasma viscosity in patients
      undergoing coronary angiography, suggesting a relation with plasma proteins and
      activation of circulating platelets or peripheral consumption of platelets. To
      evaluate this relation further controlled studies also in patients with acute
      coronary syndromes are warranted.

PMID- 20134092
TI  - Erythrocyte aggregation at non-steady flow conditions: a comparison of
      characteristics measured with electrorheology and image analysis.
AB  - In the present study electro-rheology (Contraves LS30 viscometer-based system)
      and optical shearing microscopy (Lincam CSS450 system and image analysis)
      techniques have been utilized in order to provide quantitative data on the
      behaviour of the microstructural properties of whole normal human blood at non
      steady flow conditions. The objective of this work is to contribute towards a
      better understanding of red blood cell aggregation at flow conditions similar to
      that occurring in a circulatory system and to aid the interpretation and
      validation of electro-rheological data through a quantitative comparison with
      data acquired with optical shearing microscopy. Electro-rheology is a promising
      technique that has been used to provide bulk fluid properties, showing potential
      for basic research and diagnostic purposes, whereas optical shearing techniques
      offer a direct assessment of blood microstructure at a cellular level. However,
      little information exists in the literature regarding the relationships between
      electro-rheological measurements and blood microstructural characteristics. The
      results showed that the different non-steady flow conditions affect differently
      the dynamics of aggregation varying from a parabolic-decrease to an inverted S
      shape curve with time. For a wide range of the non-steady flows results obtained
      with the two different techniques agree to a difference between 1.2 and 12%.

PMID- 20134093
TI  - Blood pressure directly correlates with blood viscosity in diabetes type 1
      children but not in normals.
AB  - OBJECTIVE: To determine the relationship between mean arterial blood pressure
      (MAP) and blood viscosity in diabetic type 1 children and healthy controls to
      investigate whether MAP is independent of blood viscosity in healthy children,
      and vice versa. RESEARCH DESIGN AND METHODS: Children with diabetes type 1
      treated by insulin injection were studied. Controls were healthy children of both
      sexes. MAP was calculated from systolic and diastolic pressure measurements.
      Blood viscosity was determined indirectly by measuring blood hemoglobin (Hb)
      content. The relationship between Hb, hematocrit (Hct) and blood viscosity was
      determined in a subgroup of controls and diabetics selected at random. RESULTS:
      21 (10.6+/-2.5 years) type 1 diabetic children treated with insulin and 25
      healthy controls age 9.6+/-1.7 years were studied. Hb was 13.8+/-0.8 g/dl in
      normal children vs. 14.3+/-0.9 g/dl in the diabetic group (p<0.05). MAP was
      71.4+/-8.2 in the normal vs. 82.9+/-7.2 mmHg in the diabetic group (p<0.001).
      Glucose was 89.3+/-10.6 vs. 202.4+/-87.4 mg/dl respectively. Diabetics had a
      positive MAP/Hb correlation (p=0.007), while normals showed a non significant
      (p=0.2) negative correlation. The blood viscosity/Hb relationship was studied in
      a subgroup of 8 healthy controls and 8 diabetic type 1 children. There was no
      significant difference in Hb and Hct between groups. Diabetics showed a trend of
      increasing blood viscosity (+7%, p=0.15). CONCLUSIONS: Normal children compensate
      for the increase in vascular resistance due to increased blood viscosity
      (increased Hb and Hct) while diabetic children do not, probably due to
      endothelial dysfunction.

PMID- 20134094
TI  - An overview about erythrocyte membrane.
AB  - In the sixties and seventies, erythrocytes or red blood cells (RBCs) were
      extensively studied. Much has been learnt particularly concerning their
      metabolism and gas transporter function.In the past decade, the use of new
      approaches and methodologies, such as proteomic analysis, has contributed for a
      renewed interest on the erythrocyte. Recent studies have provided us with a more
      detailed and comprehensive picture on the composition and organization of its
      cellular membrane that will be the main subject of this minireview. Unexpectedly,
      it has been recognized that this cell expresses several adhesion molecules on its
      surface, like other cellular types such blood circulating cells or endothelial
      cells. Taking into consideration the cellular functions of the erythrocyte, the
      clarification of the role of those adhesion molecules may in the future open new
      horizons for the biological significance of this cellular player.

PMID- 20134095
TI  - Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis.
AB  - Angiotensin-converting enzyme 2 (ACE2), a first homolog of ACE, regulates the
      renin-angiotensin system by counterbalancing ACE activity. Accumulating evidence
      in recent years has demonstrated a physiological and pathological role of ACE2 in
      the cardiovascular, renal and respiratory systems. For instance, in the acute
      respiratory distress syndrome (ARDS), ACE, AngII, and AT1R promote the disease
      pathogenesis, whereas ACE2 and the AT2R protect from ARDS. Importantly, ACE2 has
      been identified as a key SARS-coronavirus receptor and plays a protective role in
      SARS pathogenesis. Furthermore, the recent explosion of research into the ACE2
      homolog, collectrin, has revealed a new physiological function of ACE2 as an
      amino acid transporter, which explains the pathogenic role of gene mutations in
      Hartnup disorder. This review summarizes and discusses the recently unveiled
      roles for ACE2 in disease pathogenesis.

PMID- 20134096
TI  - Double-blind and placebo-controlled study of the effectiveness and safety of
      extracorporeal cardiac shock wave therapy for severe angina pectoris.
AB  - BACKGROUND: Low-energy shock wave (SW) therapy has improved myocardial ischemia
      in both a porcine model and in patients with severe angina pectoris. METHODS AND
      RESULTS: To further confirm the effectiveness and safety of SW therapy, 8
      patients with severe angina pectoris were treated with SW therapy in a double
      blind, placebo-controlled and cross-over manner. SW therapy, but not placebo,
      significantly improved chest pain symptoms and cardiac function without any
      complications or adverse effects. CONCLUSIONS: Extracorporeal cardiac SW therapy
      is an effective, safe and non-invasive therapeutic option for severe angina
      pectoris.

PMID- 20134097
TI  - Significance of maximal and regional left ventricular wall thickness in
      association with arrhythmic events in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Increased maximal left ventricular wall thickness (LVWT; >30 mm) is a
      marker of risk for sudden cardiac death in hypertrophic cardiomyopathy (HCM).
      Patients with mild left ventricular hypertrophy (LVH) are not free of events.
      Regional heterogeneity of LVH may contribute to arrhythmic vulnerability. METHODS
      AND RESULTS: 157 HCM patients underwent assessment of maximal and regional LVWT
      by 2-dimensional echocardiography, and arrhythmic burden in a follow-up of a
      median 3.7 years. 45 patients with ventricular arrhythmic events (VAEs+ group)
      had larger maximal LVWT and regional LVWTs (basal anterior-B12 and equatorial
      inferior-EQ6 segments, P=0.05). Maximal LVWT and B12 above a cut-off value of 15
      mm were associated with a significant 4.5-fold (95% confidence interval (CI) 1.1
      18.8, P=0.04), 3.2-fold (95%CI 1.5-6.7, P<0.002), and EQ6 above 19 mm with 5.9
      fold (95%CI 2.0-16.9, P<0.001) increased the relative risk of VAEs. Multivariate
      analysis identified the 2 regional measures as the only predictors, independently
      associated with arrhythmic risk. CONCLUSIONS: Non-invasive imaging measures, such
      as LVWT, do have a role in identifying the patients at risk of VAEs. In addition
      to maximal LVWT, the key regional LVWTs provide complementary information of
      incremental value to the conventional risk stratification model.

PMID- 20134098
TI  - Green tea catechins improve human forearm endothelial dysfunction and have
      antiatherosclerotic effects in smokers.
AB  - BACKGROUND: Because green tea reduces cardiovascular and cerebrovascular risk,
      the purpose of this study aimed to elucidate the effect of green tea catechins
      (GTC) on endothelial dysfunction in smokers. METHODS AND RESULTS: The 30 healthy
      male smokers were divided into 3 groups and given green tea beverages containing
      0 mg (control group), 80 mg (medium-dose group) or 580 mg (high-dose group) of
      GTC daily for 2 weeks. Endothelial-dependent and- independent vasodilatation was
      investigated by measuring the forearm blood flow (FBF) responses to acetylcholine
      and sodium nitroprusside using venous occlusion strain-gauge plethysmography. The
      FBF response to acetylcholine significantly increased at 2 h and 1 and 2 weeks
      after GTC intake in the high-dose group, but no increase was observed in the
      other groups. FBF responses to sodium nitroprusside did not alter in any group at
      any time point. A significant increase in plasma nitric oxide and a decrease in
      asymmetrical dimethylarginine, malondealdehyde and 4-hydroxynonenal, C-reactive
      protein, monocyte chemotactic protein-1, and soluble CD40 ligand levels were
      detected after chronic consumption of high-dose GTC. CONCLUSIONS: GTC have
      antiatherosclerotic effects on dysfunctional vessels in smokers through
      increasing the level of nitric oxide and reducing oxidative stress.

PMID- 20134099
TI  - Atorvastatin downregulates monocyte CD36 expression, nuclear NFkappaB and
      TNFalpha levels in type 2 diabetes.
AB  - AIM: Type 2 diabetes increases the risk for cardiovascular disease, and 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce
      cardiovascular events in these patients. The benefits of statin therapy cannot be
      explained only by the lipid-lowering effect. The aim of this study was to test
      the effect of atorvastatin therapy on CD36 scavenger receptor expression, nuclear
      factor-kappaB (NFkappaB) levels and markers of inflammation (C-reactive protein,
      CRP, Tumor Necrosis Factor-alpha, TNF-alpha) in circulating monocytes from
      diabetic patients. METHODS: Twenty-two type 2 diabetic patients were treated for
      8 weeks with atorvastatin (20 mg/day). At baseline and after treatment a blood
      sample was collected for measurement of glucose, lipid profile (total
      cholesterol, HDL, LDL cholesterol, triglycerides), glycated hemoglobin (HbA1c),
      CRP and for isolation of monocytes. RESULTS: Atorvastatin decreased total
      (p<0.0001) and LDL (p<0.01), and incresased HDL choles-terol (p<0.02). CD36
      surface protein expression (anti-CD36 fluorescein isothiocyanate-FITC) was
      reduced in circulating monocytes after atorvastatin therapy (p<0.02) while
      immunoblot analysis showed reduced nuclear and increased cytoplasm NFkappaB
      levels (p<0.05). Finally, TNFalpha production in lipopolysaccharide-activated
      monocytes from patients treated with atorvastatin was reduced (p<0.05).
      CONCLUSION: These results suggest that atorvastatin therapy, beside lowering
      serum cholesterol levels, could exert anti-atherogenic and anti-inflammatory
      effects in type 2 diabetic patients.

PMID- 20134100
TI  - Associations between plasma C-reactive protein levels and the severities of
      coronary and aortic atherosclerosis.
AB  - AIM: Limited correlations between C-reactive protein (CRP) and coronary artery
      disease (CAD) have been reported. Recently, MRI became a useful tool for non
      invasively evaluating atherosclerotic plaques in thoracic and abdominal aortas.
      METHODS: To elucidate the associations between plasma CRP levels and the
      severities of coronary and aortic atherosclerosis, we performed aortic black
      blood MRI in 136 patients undergoing coronary angiography. For each patient, 9
      slices of thoracic aorta and 9 slices of abdominal aorta were obtained at 12-mm
      intervals, and the plaque extent in each slice was scored. The degree of aortic
      atherosclerosis is represented as the sum of scores. The degree of coronary
      atherosclerosis is represented as the number of >50% stenotic vessels and >25%
      stenotic segments. RESULTS: CAD (>50% stenosis) was present in 96 patients.
      Patients with CAD had higher CRP levels than those without CAD (median 0.78 vs.
      0.48 mg/L, p<0.02). CRP levels tended to increase depending on the number of
      stenotic vessels: 0.48, 0.70, 0.74, and 0.88 mg/L (p=NS). CRP correlated weakly
      with the number of stenotic segments (r=0.21). Regarding aortic atherosclerosis,
      136 patients were divided into quartiles by plaque score. CRP levels increased
      stepwise in quartiles: 0.40, 0.56, 1.08, and 1.10 mg/L (p<0.001). CRP levels also
      correlated with the plaque score (r=0.38). In multivariate analysis, aortic
      atherosclerosis was an independent factor for CRP levels, but coronary
      atherosclerosis was not. CONCLUSION: Plasma CRP levels correlated with the
      severities of both coronary and aortic atherosclerosis, but CRP levels are more
      likely to reflect the severity of aortic atherosclerosis than coronary
      atherosclerosis.

PMID- 20134101
TI  - Is pentraxin 3 involved in obesity-induced decrease in arterial distensibility?
AB  - AIM: Obesity is a strong risk factor for cardiovascular morbidity and mortality.
      In addition, decreased central arterial distensibility is recognized as an
      independent risk factor for cardiovascular disease (CVD). Obese subjects exhibit
      low arterial distensibillity; however, the mechanism responsible for the decrease
      in arterial distensibility in obese subjects has not yet been elucidated.
      Pentraxin 3 (PTX3), a recently identified member of the pentraxin family of
      proteins, is produced in areas of atherosclerosis. A recent study has revealed
      that the PTX3 level may indicate the vascular inflammatory status. The aim of
      this study was to investigate plasma PTX3 concentrations and arterial
      distensibility in obese subjects. METHODS: Eleven obese men (age: 44+/-2 years,
      body mass index [BMI]: 32+/-1 kg/m(2)) and 14 nonobese men (age: 42+/-2 years,
      BMI: 26+/-1 kg/m(2)) participated in this study. We measured arterial compliance
      (using simultaneous B-mode ultrasound and arterial applanation tonometry of the
      common carotid artery); beta-stiffness index, an index of arterial compliance
      adjusted for distending pressure; and plasma PTX3 concentrations. RESULTS:
      Arterial compliance was significantly lower and the beta-stiffness index was
      significantly higher in obese men than in non-obese men. Plasma PTX3
      concentration was markedly higher in obese than non-obese men. CONCLUSIONS: Obese
      men have lower arterial distensibility and higher circulating PTX3 levels than
      non-obese men; therefore, higher PTX3 levels and decreased arterial
      distensibility coexist in obese men. The high PTX3 concentrations in obese men
      may be involved in the mechanism underlying the obesity-induced decrease in
      arterial distensibility.

PMID- 20134102
TI  - Genetic risk factors and the anti-atherosclerotic effect of pioglitazone on
      carotid atherosclerosis of subjects with type 2 diabetes--a retrospective study.
AB  - AIM: Pioglitazone, an agonist of peroxisome proliferator-activated receptor
      gamma, showed various anti-atherosclerotic effects on type 2 diabetic patients.
      This retrospective study was done to ascertain which risk factor(s) associate
      with anti-atherosclerotic effects of pioglitazone. METHODS: We enrolled 160
      diabetic patients treated through diet only and 62 treated with pioglitazone and
      annually evaluated carotid maximum (MaxIMT) and averaged intima-media thickness
      (AveIMT) for 2 years. We analyzed the relation of 99 single-nucleotide
      polymorphisms (SNP) as well as conventional risk factors with the progression or
      regression of carotid atherosclerosis. RESULTS: The D allele of the angiotensin
      converting enzyme (ACE) gene and 677 allele of the methylene-tetrahydrofolate
      reductase (MTHFR) gene showed a significant association with increases in MaxIMT
      among the diabetic subjects treated through diet only. The pioglitazone-treated
      carriers of the D allele showed an attenuation of MaxIMT as compared with the
      diet-treated carriers. The pioglitazone-treated carriers of the 677T allele
      carriers showed a significant attenuation of MaxIMT compared with the diet
      treated carriers. CONCLUSIONS: Pioglitazone may exert anti-atherosclerotic
      effects on type 2 diabetics carrying the ACE gene's D allele and/or MTHFR gene's
      677T allele, who showed a progression of carotid atherosclerosis without the
      drug.

PMID- 20134103
TI  - [Globally harmonized system of classification and labelling of chemicals (GHS)
      and its implementation in Japan].
AB  - The Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
      is a set of recommendations by the United Nations, first issued in 2003 as a
      communication tool for the sound management of chemicals, comprising harmonized
      classification criteria for physical, health and environmental hazards, a unified
      format for material safety data sheets (MSDS), and labeling elements including
      pictograms and hazard statements preassigned to each classification category. The
      GHS has been introduced into Japan and implemented in the regulatory framework
      for chemical safety. The Japanese Industrial Standards (JIS) adopted the GHS, and
      the GHS-based JIS rules have become the Japanese standards for labels and MSDS.
      The use of the JIS format for labels and MSDS is recommended by several competent
      authorities in Japan although mostly on a voluntary basis. In the workplace,
      however, GHS-based JIS labels and MSDS have become legal requirements by the
      Industrial Safety and Health Law since 2006; namely, issuing MSDS in such a
      format is mandatory for the 640 specified chemicals and also labeling for the 99
      targeted chemicals*. Although the GHS provides definitions and classification
      criteria for 10 classes of health hazards (acute toxicity, skin and eye
      corrosion/irritation, sensitization, germ cell mutagenicity, carcinogenicity,
      reproductive toxicity, specific target organ toxicity single/repeated exposures,
      and aspiration hazard), it does not provide actual classification of chemicals,
      so that competent authorities and industries need to classify a number of
      chemicals and/or mixtures. Weight-of-evidence judgment and/or expert judgment
      would be necessary in many cases. In this paper, the outline of the GHS
      classification is described and problems of the GHS and its implementation are
      discussed.

PMID- 20134104
TI  - [Recent development in animal testing to predict the skin and respiratory
      sensitizing potential of chemicals].
AB  - The identification of chemicals with skin and/or respiratory sensitizing
      potential is important for the prevention of allergic diseases in both living and
      work environments. Although a number of animal models for respiratory allergic
      diseases have been reported, none of these models meets the goals of broad
      assessments of chemical sensitizing potential. We are attempting to develop a
      test for predicting the respiratory sensitization of chemicals. In the evaluation
      of skin sensitization of chemicals, the mostly used predictive tests are the
      guinea pig maximization test, Buehler test, and mouse local lymph node assay
      (LLNA). However, only LLNA has been validated formally and independently. Recent
      studies have revealed that EC3 estimated by LLNA correlates well with human skin
      sensitizing potency and the threshold for the induction of skin sensitization in
      the human repeat patch test. Thus, LLNA can predict the potency of skin
      sensitizing potential of a chemical and its risk in humans.

PMID- 20134105
TI  - [Skin sensitizers in cosmetics and skin care products].
AB  - Cosmetics are defined as "articles with mild action on the human body, which are
      intended to be applied to the human body through rubbing, sprinkling or other
      methods, aiming to clean, beautify and increase the attractiveness, alter the
      appearance or to keep the skin or hair in good condition (The Pharmaceutical
      Affairs Law: Article 2)." Consequently, they include personal hygiene products
      such as shampoos, soaps and toothpaste. In Europe, 1% of the population is
      estimated to be allergic to fragrances and 2-3% to ingredients of cosmetics; 10%
      of outpatients patch-tested for cosmetics allergy were found to be positive.
      Allergenic ingredients of cosmetics can be fragrances, hair dye, preservatives,
      antioxidants, emollients, surfactants, UV absorbers, pigments or resins used in
      nail cosmetics. Among standard allergen series, eight substances are related to
      cosmetics; in Japan in 2003, p-phenylenediamine (hair dyes) induced allergic
      reactions with the highest rate of 7.9% in outpatients patch-tested (n=805),
      followed by fragrance mix No. 1 (4.0%, mixture of eight fragrances frequently
      used), colophony (3.2%, main contents of pine resin), lanolin alcohol
      (2.7%,emollients), and formaldehyde, parabens, Kathon CG (2.7% ,1.9% and 1.0%,
      respectively; preservatives). Cosmetic allergy symptoms tend to be mild except
      those caused by hair dye. However, the population exposed to cosmetics is huge
      and the number of ingredients used in cosmetics increased up to more than 6000.
      Here, major cosmetic ingredient allergens, mainly reported in Japan, are reviewed
      and discussed.

PMID- 20134106
TI  - [Preventive measures against health damage due to chemicals in household
      products].
AB  - Chemicals in household products have been paid much attention as the main cause
      of health damage in consumers, such as allergic contact dermatitis. Preventive
      measures against health damage due to chemicals in fabrics, plastics and rubber
      products for household use, are reviewed, focusing on 1) the incidence of health
      damage due to household products, 2) causative product-chemical investigation,
      and 3) case studies on skin damage.

PMID- 20134107
TI  - [Toward a more rational field-genetic epidemiology].
AB  - Genetic dissection of diseases is one of the epoch-making achievements in modern
      medicine. Positional cloning is a key method to isolate disease-related genes.
      For positional cloning, there are two conventional methods: family-based studies
      and case-control studies. In this review, I would like to describe several family
      based studies on single gene diseases which I had conducted including those of
      Akita diabetic mice, systemic carnitine deficiency and Hartnup disease. The study
      of systemic carnitine deficiency underscored a potential power of the "Carrier
      state." Furthermore, cultural and public health practices in Japan such as
      preservation of umbilical cords and mother and child passbooks enabled us to
      conduct linkage analysis even 20 years after the deaths of affected patients in
      Hartnup disease. For multifactorial diseases, I present three family-based
      studies: intracranial aneurysm, moyamoya and arteriovenous malformation. Finally,
      I discuss on theoretical issues concerning the relationship among odds ratio,
      phenocopy rate and penetrance by formulating a single-locus dominant association
      model. Analysis of the model predicted a notion that a large odds ratio
      facilitates familial clustering of multifactorial diseases and vice versa is the
      case. Furthermore, the analysis predicted that genetic markers for screening
      should have odds ratio >/= eight to maintain similar qualities commonly required
      for clinical tests. Collectively, the analysis predicted a two-stage study design
      composed of linkage analysis based on a family study and subsequent replication
      by a case-control association study is more rational than the currently used two
      independent case-control design. This newly proposed method is expected to
      provide polymorphisms, which have large odds ratios, requiring only minimum
      research budgets.

PMID- 20134108
TI  - [Predicting spread of new pandemic swine-origin influenza A (H1N1) in local mid
      size city: evaluation of hospital bed shortage and effectiveness of vaccination].
AB  - OBJECTIVES: On April 24th, 2009, a new swine-origin influenza A (H1N1) was first
      reported in Mexico. Japan confirmed cases of the flu on May 9th, and the pandemic
      in Japan has become full-scale. The Ministry of Health, Labor and Welfare of
      Japan announced that the first peak of this pandemic was predicted to occur in
      October, 2009. Therefore, it is most important to predict the progress of this
      pandemic to be able to use medical resources effectively in Japan. METHODS: We
      used a modified susceptible-exposed-infected-recovered (SEIR) model to calculate
      the number of infected people and hospital bed shortage during this pandemic. In
      this model, available medical resources were investigated on the basis of four
      vaccination scenarios. RESULTS: Our model showed that it would take a further six
      months for the pandemic to peak than was predicted by the Ministry of Health,
      Labor and Welfare of Japan. Without vaccination, at the peak of the pandemic
      23,689 out of 400,000 people would be infected and the hospital bed shortage
      would reach 7,349 in total. CONCLUSIONS: We suggest that mathematical models are
      strong tools to predict the spread of infectious diseases. According to our
      model, it is possible to prevent hospital bed shortage by vaccination.

PMID- 20134109
TI  - [Estimates of reduction in prevalence of diabetes mellitus and health care costs
      reduced through the intervention program for obese people in Japan].
AB  - OBJECTIVES: In the structural reform bill of health care, which passed the Diet
      in fiscal year 2006, the number of patients with lifestyle-related diseases and
      the number of those who will potentially develop such diseases in 2015 should be
      reduced by 25% from the number in 2008 through the national intervention program
      against obesity. We estimated the reduction in prevalence of diabetes mellitus,
      as a representative lifestyle-related disease, and the health care costs reduced
      by controlling obesity. METHODS: Firstly, we estimated the prevalence (95%
      confidence interval) of obese people by conducting the National Health and
      Nutrition Examination Survey in 2005. Secondly, we estimated the proportion of
      obese people that should be reduced in order to reduce diabetes prevalence by 25%
      using the data from the National Diabetic Patients Survey in 2002. Thirdly, we
      estimated changes in prevalence of diabetes mellitus when the proportion of obese
      people was reduced by 20%, 40%, 60%, 80%, and 100%. Finally, we estimated how
      much health care costs would be reduced if the number of obese people was reduced
      by 20%. RESULTS: It is extremely difficult to reduce the prevalence of diabetes
      mellitus by 25% by only reducing the proportion of obese people. From our
      estimation of changes in the prevalence of diabetes mellitus when the proportion
      of obese people was reduced, the intervention for people aged from 40 years to 59
      years was more effective than that for people in other age groups for both male
      and female. The health care costs of diabetes mellitus can be reduced by yen
      841,210,000,000 for male and by yen 75,930,000,000 for female. CONCLUSION: It is
      almost impossible to reduce the prevalence of diabetes mellitus by 25% although
      it is cost-effective to target on people aged from 40 to 59 years against obesity
      to reduce the prevalence of diabetes mellitus.

PMID- 20134110
TI  - [Attitudes towards the code of conduct for scientists among council members of
      the Japanese Society for Hygiene].
AB  - OBJECTIVES: The aim of this study was to clarify the attitudes towards the code
      of conduct for scientists among council members of the Japanese Society for
      Hygiene (JSH). We also aimed to collect information to be used as baseline data
      for future studies. METHODS: From November to December 2007, 439 Council members
      of the Japanese Society for Hygiene completed a self-administered questionnaire.
      RESULTS: The valid response rate was 43.7% (n=192/439). The mean ages of the
      subjects were 56.2 years for males (n=171), and 53.0 years for females (n=19).
      Many council members were unfamiliar with the "Code of Conduct for Scientists"
      established by the Science Council of Japan, suggesting that most of the regular
      members were also unfamiliar with these guidelines. However, the high level of
      interest in the "Code of Conduct for Scientists" established by the Science
      Council of Japan indicated a positive attitude towards learning about research
      ethics. Moreover, one-half of the subjects responded that JSH should establish a
      code of conduct for scientists. Below are some of the reasons for requiring JSH
      to establish a code of conduct: 1. Private information is prevalent in the field
      of hygiene. 2. The overall stance as an academic society would be established and
      would encourage individuality in academic societies. 3. Members have various
      backgrounds within the field of hygiene, and they should have a code of conduct
      different from that of their institution of affiliation. CONCLUSION: We clarified
      attitudes towards the Code of Conduct for Scientists among council members of the
      Japanese Society for Hygiene.

PMID- 20134111
TI  - The forefront for novel therapeutic agents based on the pathophysiology of lower
      urinary tract dysfunction: pathophysiology of voiding dysfunction and
      pharmacological therapy.
AB  - Normal lower urinary tract function consists of voiding and storage. During
      voiding, the pontine micturition reflex center orders the sacral parasympathetic
      nucleus to increase parasympathetic activity, resulting in urinary bladder
      detrusor contraction via activation of post-synaptic muscarinic receptors (M2/3)
      and in the relaxation of both urethral and prostatic smooth muscle by nitric
      oxide (NO). In addition, the rhabdosphincter relaxes by inhibition of the
      pudendal nucleus at the sacral portion. During the storage phase, increase in
      sympathetic activity relaxes the urinary bladder via activation of post-synaptic
      beta(3)-receptors and in the contraction of both urethral and prostatic smooth
      muscles via alpha(1)-adrenoceptor. Many factors influence voiding function,
      including lower urinary tract disorders (benign prostatic hyperplasia in males,
      urethral stricture) and neurological disorders (central and peripheral). Theories
      of pharmacotherapy for voiding dysfunction are 1) increase detrusor contractility
      and 2) decrease urethral resistance. The former includes agonists for muscarinic
      receptors and cholinesterase inhibitor; and the latter includes alpha(1)
      adrenoceptor antagonists, NO donors, benzodiazepines, baclofen, dantrolene, and
      boturinum toxin.

PMID- 20134112
TI  - The forefront for novel therapeutic agents based on the pathophysiology of lower
      urinary tract dysfunction: alpha-blockers in the treatment of male voiding
      dysfunction - how do they work and why do they differ in tolerability?
AB  - alpha(1)-Adrenoceptor antagonists are the mainstay of medical treatment of male
      voiding dysfunction which typically is attributed to benign prostatic
      hyperplasia. While original concepts have assumed that they relieve voiding
      dysfunction by relaxing prostatic smooth muscle, newer data indicate that their
      therapeutic effects at least partly occur independent of prostatic relaxation,
      perhaps involving direct effects on blood vessels, urothelium, afferent nerves,
      and/or smooth muscle of the urinary bladder. The adverse event profiles differ
      among alpha(1)-adrenoceptor antagonists, with tamsulosin having a particularly
      good cardiovascular tolerability. While this was originally attributed to its
      selectivity for alpha(1A)-adrenoceptors, it appears that alfuzosin which lacks
      subtype-selectivity, has a very similar tolerability. In contrast, doxazosin and
      terazosin, which are chemically and pharmacologically more closely related to
      alfuzosin than to tamsulosin, appear to have more side effects attributable to
      the cardiovascular system. More recent data indicate that tolerability
      differences between alpha(1)-adrenoceptor antagonists may at least partly relate
      to pharmacokinetic rather than to pharmacodynamic differences. Taken together,
      these data emphasize the idea that concepts about drug efficacy and tolerability
      despite being highly plausible may not necessarily be true and always require
      thorough experimental testing.

PMID- 20134113
TI  - The forefront for novel therapeutic agents based on the pathophysiology of lower
      urinary tract dysfunction: bladder selectivity based on in vivo drug-receptor
      binding characteristics of antimuscarinic agents for treatment of overactive
      bladder.
AB  - We have reviewed the binding of antimuscarinic agents, used to treat urinary
      dysfunction in patients with overactive bladder, to muscarinic receptors in
      target and non-target tissues in vivo. Transdermal administration of oxybutynin
      in rats led to significant binding in the bladder without long-term binding in
      the submaxillary gland and the abolishment of salivation evoked by oral
      oxybutynin. Oral solifenacin showed significant and long-lasting binding to
      muscarinic receptors in mouse tissues expressing the M(3) subtype. Oral
      tolterodine bound more selectively to muscarinic receptors in the bladder than in
      the submaxillary gland in mice. The muscarinic receptor binding activity of oral
      darifenacin in mice was shown to be pronounced and long-lasting in the bladder,
      submaxillary gland, and lung. In vivo quantitative autoradiography using (+)N
      [(11)C]methyl-3-piperidyl benzilate in rats showed significant occupancy of brain
      muscarinic receptors on intravenous injection of oxybutynin, propiverine,
      solifenacin, and tolterodine. The estimated in vivo bladder selectivity compared
      to brain was significantly greater for solifenacin and tolterodine than
      oxybutynin. Darifenacin occupied few brain muscarinic receptors. Similar findings
      were also observed with positron emission tomography in conscious rhesus monkeys.
      The newer generation of antimuscarinic agents may be advantageous in the bladder
      selectivity after systemic administration.

PMID- 20134114
TI  - The forefront for novel therapeutic agents based on the pathophysiology of lower
      urinary tract dysfunction: ameliorative effect of solifenacin succinate
      (Vesicare), a bladder-selective antimuscarinic agent, on overactive bladder
      symptoms, especially urgency episodes.
AB  - Overactive bladder (OAB) syndrome is a common condition that is most often
      observed in the elderly. Pharmacological treatment with muscarinic receptor
      antagonists has been most widely used for OAB. An antimuscarinic agent,
      solifenacin, showed the highest affinity for the muscarinic M(3) receptor, which
      mediates urinary bladder contraction. In preclinical studies, solifenacin
      exhibited a highly bladder-selective profile compared with other antimuscarinic
      agents. Solifenacin was also shown to increase bladder capacity without affecting
      residual urine in an OAB model of rats. Urgency is now considered to result from
      overactivation of afferent nerves from the urinary bladder. It has been reported
      that afferent nerves are located adjacent to the urothelium, and stimulation of
      muscarinic receptors expressed on the urothelium may contribute to the activation
      of afferent nerves via non-neuronal ATP release. Solifenacin produces its
      inhibitory effect on bladder afferent activity partly via the suppression of non
      neuronal ATP release. Clinically, solifenacin ameliorates all symptoms in OAB
      patients; and in particular, it produces a significant decrease in urgency
      episodes, which is the principal symptom of OAB. The pharmacological profile of
      solifenacin is therefore considered to contribute to its beneficial effects of
      high efficacy against OAB symptoms with good tolerability.

PMID- 20134115
TI  - The forefront for novel therapeutic agents based on the pathophysiology of lower
      urinary tract dysfunction: pathophysiology and pharmacotherapy of overactive
      bladder.
AB  - Overactive bladder (OAB) syndrome, which is characterized by a complex of storage
      symptoms (urinary urgency, frequency, nocturia, and urgency incontinence) is
      highly prevalent within the general population, causing major distress to
      patients in terms of their psychosocial and physical functioning. Muscarinic
      receptors of bladder smooth muscles are involved in both normal and disturbed
      bladder contraction. The muscarinic receptor functions may change in bladder
      disorders associated with OAB, implying that mechanisms, which normally have
      little clinical importance, may be up-regulated and contribute to the
      pathophysiology of OAB. In addition, several reports have suggested that various
      stimulations release many substances, including adenosine triphosphate,
      prostaglandins, nitric oxide, and acetylcholine, from bladder urothelium, which
      contribute to pathophysiology of the increased bladder sensation, OAB symptoms,
      and detrusor overactivity. Bladder urothelium possesses a non-neuronal
      cholinergic system and high density of muscarinic receptors. The roles and
      functions of the non-neuronal cholinergic system in OAB are now being evaluated.
      In the pharmacotherapy of OAB, antimuscarinic agents are the first choice drugs.
      Furthermore, new therapeutic targets at the levels of the urothelium, detrusor
      muscles, autonomic and afferent pathways, spinal cord, and brain are proposed. In
      this review, the pathophysiology of OAB, especially the role of non-neuronal
      acetylcholine, is discussed. In addition, new drugs with new action mechanisms
      will be introduced.

PMID- 20134116
TI  - A novel CC-chemokine receptor 3 antagonist, Ki19003, inhibits airway eosinophilia
      and subepithelial/peribronchial fibrosis induced by repeated antigen challenge in
      mice.
AB  - CC-chemokine receptor 3 (CCR3) is a chemokine receptor for which major ligands,
      CC-chemokine ligand (CCL) 11, CCL24, and CCL26, are known to be involved in
      chemotaxis for eosinophils. In the present study, we evaluated the effect of a
      low molecular weight CCR3-receptor antagonist, Ki19003 (4-[[5-(2,4
      dichlorobenzylureido)pentyl][1-(4-chlorophenyl)ethyl]amino]butanoic acid), on
      airway remodeling in a mouse model of allergic asthma. BALB/c mice were
      sensitized twice by intraperitoneal injection of ovalbumin (OA) and exposed daily
      to 1% OA for 3 weeks. Twenty-four hours after the final antigen challenge,
      bronchoalveolar lavage and histological examinations were carried out. Ki19003
      clearly inhibited antigen-induced increase in the number of eosinophils in
      bronchoalveolar lavage fluid (BALF), but did not affect the number of other cell
      types examined in this study. Ki19003 also inhibited the increased production of
      transforming growth factor-beta1 in BALF and the amount of hydroxyproline in the
      lungs in a dose-dependent manner. Furthermore, Ki19003 significantly attenuated
      allergen-induced subepithelial and peribronchial fibrosis. These findings
      indicate that CCR3 antagonism prevents not only the infiltration of eosinophils
      into the airways but also the development of allergen-induced subepithelial and
      peribronchial fibrosis. Therefore, a CCR3 antagonist may be useful in the
      treatment of airway remodeling, especially subepithelial and peribronchial
      fibrosis, in allergic asthma.

PMID- 20134117
TI  - Effect of erythropoietin on angiogenesis with the increased adhesion of platelets
      to the microvessels in the hind-limb ischemia model in mice.
AB  - Erythropoietin (EPO) has been shown to enhance angiogenesis, but its precise
      mechanisms of enhancement during ischemia are not fully elucidated. We examined
      the effect of EPO on blood flow recovery from acute hind-limb ischemia induced by
      ligation of the femoral artery in male C57Bl/6 mice. The density of microvessels
      with platelet adhesion in ischemic tissues was assessed by intravital microscopy.
      Treatment with EPO (100 and 1000 IU/kg, i.p.) restored blood flow in a dose
      dependent manner and increased plasma levels of soluble-P-selectin, vascular
      endothelial growth factor (VEGF), and stromal cell-derived factor (SDF-1). Flow
      cytometric analysis revealed increased P-selectin expression on platelets in EPO
      treated mice compared to PBS-treated mice. Intravital microscopic studies showed
      that EPO increased density of microvessels with platelet adhesion selectively in
      the ischemic tissues. Neutralizing antibody against P-selectin reduced the
      density of microvessels with platelet adhesion enhanced with EPO and impaired
      blood flow recovery with reductions in VEGF and SDF-1 levels. These results
      suggest that EPO administration enhances recovery from hind-limb ischemia, and
      platelet adhesion to the microvessels is a key event to enhance the angiogenesis
      in the ischemic tissues.

PMID- 20134118
TI  - MMHD [(S,E)-2-methyl-1-(2-methylthiazol-4-yl) hexa-1,5-dien-ol], a novel
      synthetic compound derived from epothilone, suppresses nuclear factor-kappaB
      mediated cytokine expression in lipopolysaccharide-stimulated BV-2 microglia.
AB  - The effects of MMHD [(S,E)-2-methyl-1-(2-methylthiazol-4-yl) hexa-1,5-dien-ol], a
      novel synthetic compound derived from epothilone, was investigated for its
      effects on the expression of proinflammatory mediators in lipopolysaccharide
      stimulated BV-2 microglia. MMHD attenuated the expressions of inducible nitric
      oxide synthase and cyclooxygenase-2 mRNA and protein without affecting cell
      viability. Moreover, MMHD suppressed nuclear factor-kappaB (NF-kappaB) activation
      via the translocation of p65 into the nucleus. These results indicate that MMHD
      exerts anti-inflammatory properties by suppressing the transcription of
      proinflammatory cytokine genes through the NF-kappaB signaling pathway.

PMID- 20134119
TI  - Effects of scrotal insulation and pathological lesions on alpha-Smooth Muscle
      Actin (SMA) and vimentin in the bull testes.
AB  - The expression patterns of alpha-smooth muscle actin (SMA) and vimentin in the
      bovine testis indicate the maturation status of seminiferous tubules. The present
      study demonstrates the effects of impaired spermatogenesis resulting from
      increased testicular temperature after scrotal insulation and pathological
      lesions in subfertile bull testes on the changes in immunohistochemical
      expression of alpha-SMA and vimentin. Scrotal insulation induced degenerative
      changes of seminiferous tubules, and subfertile bull testes demonstrated
      characteristic mixed atrophied lesions; dysplastic lesions were seen in one bull.
      The increased intensity of peritubular alpha-SMA in the dysplastic area was
      distinct and indicated shrinkage of the seminiferous tubules. The mixed atrophied
      lesions revealed unaltered expression of peritubular alpha-SMA. However,
      considerable distortion was observed in the expression of alpha-SMA in severely
      degenerated tubules after insulation, which may indicate the heat sensitivity of
      peritubular alpha-SMA or its relation with spermatogenic activity under sudden
      heat stress. The vimentin expression pattern in the degenerated tubules of post
      insulated testes was unaltered. However, the Sertoli cell-only tubules of mixed
      atrophied subfertile bull testes were characterized by an increase in vimentin of
      strong intensity resembling that in the transforming pattern, which may indicate
      the reversion of Sertoli cell maturity in such cases.

PMID- 20134120
TI  - Variation of genes encoding GGPLs syntheses among Mycoplasma fermentans strains.
AB  - The information of the biosynthesis pathways of Mycoplasma fermentans specific
      major lipid-antigen, named glycoglycerophospholipids (GGPLs), is expected to be
      some of help to understand the virulence of M. fermentans. We examined primary
      structure of cholinephosphotransferase (mf1) and glucosyltransferase (mf3) genes,
      which engage GGPL-I and GGPL-III synthesis, in 20 strains, and found four types
      of variations in the mf1 gene but the mf3 gene in two strains was not detected by
      PCR. These results may have important implications in virulence factor of M.
      fermentans.

PMID- 20134121
TI  - [How do gastroenterologists contribute to primary care?].

PMID- 20134122
TI  - [Community health and medicine for gastrointestinal disease].

PMID- 20134123
TI  - [Cooperation between hospitals and clinics for appropriate therapy of chronic
      liver disease].

PMID- 20134124
TI  - [Specialist's role of bilio-pancreatic diseases in regional medicine--early
      cancer diagnosis of bilio-pancreatic duct by means of regional communication
      pass].

PMID- 20134125
TI  - [A case of adenoid cystic carcinoma of the thoracic esophagus after neoadjuvant
      chemotherapy].
AB  - A 60-year-old man was admitted to our hospital with a tumor in the thoracic
      esophagus, and squamous cell carcinoma was detected by endoscopic biopsy. On
      computed tomography, the tumor was suspected of having invaded adjacent organs by
      so the patient was given neoadjuvant chemotherapy consisting of low-dose CDDP and
      5-FU. After 2 courses of chemotherapy, a subtotal esophagectomy was performed.
      The resected specimen showed no residual squamous cell carcinoma but another
      tumor was found in the submucosal layer which had a cribiform pattern in a solid
      nest. The tumor cells were positive for S-100 protein and an Alcian-blue-positive
      substance in the gland, so the tumor was diagnosed as an adenoid-cystic
      carcinoma.

PMID- 20134126
TI  - [A case of multiple metachronous metastases of colon cancer to the small
      intestine preoperatively diagnosed by double balloon enteroscopy and radically
      resected].
AB  - The patient was a 75-year-old woman who had undergone resection of a transverse
      colon cancer two years before. She had anemia and intestinal obstruction, and a
      diagnosis of multiple metastases to the small intestine was made by double
      balloon enteroscopy. Eleven metastatic foci were resected by partial resection of
      the jejunum and ileum. Adjuvant FOLFOX chemotherapy was given, achieving a 26
      month disease-free survival. The double balloon enteroscopy was useful in the
      definitive diagnosis of this case, and aggressive resection with adjuvant
      chemotherapy contributed to the good outcome.

PMID- 20134127
TI  - [A long-term survival case of colon cancer with multiple liver metastases treated
      with multidisciplinary therapy].
AB  - A 52-year-old man underwent abdominoperineal resection of the rectum, a partial
      hepatectomy, and intrahepatic arterial infusion chemotherapy for rectal cancer
      and liver metastases in 2001. Due to recurrent liver metastases, additional
      hepatectomies were performed in 2003 and 2005. He then underwent radiofrequency
      ablation therapy and systemic chemotherapies with mFOLFOX6 and FOLFORI. In July
      2007, positron emission tomography (PET) and computed tomography (CT) revealed a
      high level of (18)F-fluorodeoxyglucose (FDG) accumulation in the liver. After 6
      cycles of chemotherapy with bevacizumab plus mFOLFOX6, the FDG accumulation
      disappeared. The multidisciplinary therapy was effective, yielding long term
      survival of over 8 years.

PMID- 20134128
TI  - [A case of tubercular papillitis of Vater].
AB  - A 47-year-old man presented with an abnormality of the duodenum detected on a
      health check endoscopy. Further endoscopy revealed swelling of the papilla of
      Vater with a whitish exudate and surrounding small nodules, which biopsy revealed
      to be non-caseating granulomas. Colonoscopy showed typical tubercular lesions in
      the colon on the right side, so we speculated that the lesions of the papilla of
      Vater were tubercular. After the administration of anti-tubercular drugs, both
      the duodenal lesion and the colonic lesions improved. Therefore, the papilla of
      Vater lesion was diagnosed as tubercular, although such cases are extremely rare.

PMID- 20134129
TI  - [Paroxetine treatment of 3 cases of cholestatic pruritus due to gastrointestinal
      malignancy].
AB  - Recently, the antipruritic activity of the selective serotonin reuptake inhibitor
      paroxetine has been reported. We report 3 patients with severe cholestatic
      pruritus due to gastrointestinal malignancy. All of them were successfully
      treated with 10 mg oral paroxetine. The onset of the antipruritic action of
      paroxetine was observed at from several hours-two days. Paroxetine seems to be an
      effective, well-tolerated treatment for cholestatic pruritus due to
      gastrointestinal malignancy.

PMID- 20134130
TI  - [A case of primary hepatic actinomycosis].
AB  - Primary hepatic actinomycosis is relatively rare, but it should be remembered in
      the differential diagnosis of liver masses. A 66-year-old woman with right
      hypochondralgia was admitted and for detailed examination and treatment of a
      liver tumor. Abdominal ultrasonography revealed a hypoechoic lesion 55 mm in
      diameter in the anterior segment. Enhanced CT showed a deep-stained tumor in the
      early phase and a low density area in the late phase. The feeding arteries were
      the right hepatic artery and right inferior phrenic artery on abdominal
      angiography. The patient was given a diagnosis of hepatocellular carcinoma with
      invasion of the inferior lobe of the right lung. We performed a central
      bisegmentectomy of the liver and partial resection of the inferior lobe of the
      right lung. Microscopic findings of the resected specimen revealed sulfur
      granules and the tumor was diagnosed as primary hepatic actinomycosis.

PMID- 20134131
TI  - [A case of rapid-onset antimitochondrial antibody-positive autoimmune hepatitis
      possibly triggered by a urinary tract infection].
AB  - A 54-year-old woman suffered acute hepatitis after she acquired cystitis.
      Laboratory results on admission showed: AST 925, ALT 1171, ALP 623, gamma-GTP127
      IU/l, T-Bil 5.0 mg/dl, antinuclear antibodies negative, smooth muscle antibodies
      80, antimitochondrial antibodies (AMA) 80, antimitochondrial M2 antibody (AMA-M2)
      117 index, IgG 2210 mg/dl. She also had HLA-DR4 and HLA-DR8. Histological study
      of a liver biopsy specimen suggested that she had autoimmune hepatitis rather
      than primary biliary cirrhosis. When prednisolone was administered, her liver
      function immediately improved and AMA and AMA-M2 levels fell to 20 and 52
      respectively. However when cystitis recurred 4 months later, her liver function
      worsened. Laboratory findings showed AST 174, ALT 183 IU/l. Upon increasing the
      dosage of prednisolone, her liver function improved again. After the recurrence
      of hepatitis, AMA and AMA-M2 levels increased to 320 and 149 respectively. We
      speculate that the urinary tract infection triggered an autoimmune response and
      her genetic predisposition also played a crucial role in the process.

PMID- 20134132
TI  - [A case of acute pancreatitis with systemic lupus erythematosus].
AB  - A 16-year-old girl had been given a diagnosis of systemic lupus erythematosus
      (SLE) at age 4, and a diagnosis of nephrotic syndrome caused by lupus nephritis
      at age 9. Medical treatment began with steroids from age 4. She developed acute
      pancreatitis in May 2007. Abdominal computed tomography showed cystic lesions in
      the abdominal cavity, and surgical drainage was performed for intracystic
      bleeding, infection and alimentary canal perforation.

PMID- 20134133
TI  - [Overview of recent progress in clinical study of DIC].

PMID- 20134134
TI  - [Definition, concept and diagnosis of disseminated intravascular coagulation].

PMID- 20134135
TI  - [Variety of pathogenesis, clinical manifestation and classification of
      disseminated intravascular coagulation].

PMID- 20134136
TI  - [Dynamics of blood coagulation and fibrinolysis and laboratory findings in
      disseminated intravascular coagulation].

PMID- 20134137
TI  - [Messages from necrotic cells mediate linkage between inflammation and
      coagulation].

PMID- 20134138
TI  - [Disseminated intravascular coagulation in malignant neoplasms].

PMID- 20134139
TI  - [Clinical application of diagnostic criteria for acute disseminated intravascular
      coagulation to patients with critical illness, sepsis, trauma and obstetric
      disorders].

PMID- 20134140
TI  - [Treatment of disseminated intravascular coagulation].

PMID- 20134141
TI  - [Clinical study of sequential high-dose chemotherapy with in vivo rituximab
      purged stem cell autografting for mantle cell lymphoma].
AB  - Sequential high-dose chemotherapy with in vivo rituximab-purged stem cell
      autografting was designed for previously untreated mantle cell lymphoma (MCL).
      The response rate, disease-free survival (DFS), overall survival (OS) and
      toxicity were investigated in this trial. Between November 2001 and August 2008,
      five patients younger than 65 years of age with MCL at diagnosis were enrolled in
      this study. Initial chemotherapy consisted of 3 cycles of CHOP regimen followed
      by four courses of high-dose chemotherapy. During the in vivo purging phase, the
      patient was administered high-dose cyclophosphamide and cytarabine, and then each
      administration was followed by two infusions of rituximab. Molecular monitoring
      of minimal residual disease was performed by assessing DNA samples from bone
      marrow and autografted cells using PCR amplification of the bcl-1/IgH
      rearrangement. The complete response rate was 100%, and the 3-year OS and DFS
      were 100% and 100%, respectively. PCR analysis of autografted cells from four
      evaluable patients, 75% lymphoma-negative harvests were achieved following in
      vivo purging. One patient relapsed 3.2 years after treatment. The principal
      toxicity in the study was hematologic but there were no treatment-related deaths.
      Intensive high-dose sequential chemotherapy with in vivo purged stem cell support
      can achieve long-term disease-free survival for MCL.

PMID- 20134142
TI  - [Cost benefit analysis for prophylactic use of itraconazole versus fluconazole
      after hematopoietic stem cell transplantation].
AB  - Systemic fungal infection (SFI) is now one of the main causes of death from
      infective complications after hematopoietic stem cell transplantation (HSCT) and
      the role of prophylaxis of fungal infection has been established. However, there
      is no evidence evaluating the cost-benefit ratio of SFI management in Japan. To
      estimate the medical costs on prophylaxis and treatment of SFI in HSCT, we
      embarked on a randomized control prospective study of the medical cost-benefit
      ratio comparing fluconazole with itraconazole for antifungal prophylaxis in 40
      patients who received HSCT in our hospital. Despite the similarity of efficacy
      for prophylaxis, the median cost of itraconazole prophylaxis between Day-10 and
      Day+28 was significantly less than that of fluconazole. There are many patients
      who require an i.v. formulation because of non-compliance with oral
      administration after HSCT and these cases cause increased medical costs.
      Therefore, further investigation is needed not only regarding differences among
      prophylactic agents but also regarding differences in administration routes
      focusing on the cost-effectiveness of treatment.

PMID- 20134143
TI  - [Usefulness of serum plasminogen activator inhibitor-1 for diagnosis and
      monitoring of late-onset sinusoidal obstruction syndrome after allogeneic stem
      cell transplantation].
AB  - Sinusoidal obstruction syndrome (SOS) was originally defined as a clinical
      syndrome occurring by three weeks after transplantation; however, it occurs even
      after three or more weeks, and such cases are called late-onset SOS. We report
      here a case of late-onset SOS. The patient was a 17-year-old male with acute
      myeloid leukemia in second complete remission. He received a preparative regimen
      including busulfan followed by allo-peripheral blood stem cell transplantation
      from an HLA-matched sibling donor. On day 28 after transplantation, he developed
      hepatomegaly with pain. On day 33 PAI-1 level was increased. Two days later
      ascites developed, leading to a diagnosis of late-onset SOS. The symptoms
      improved with conservative therapy and the level of PAI-1 was normalized. When
      hepatic impairment appears three or more weeks after transplantation, late-onset
      SOS should be considered. PAI-1 is a useful marker for the diagnosis and follow
      up of late-onset SOS.

PMID- 20134144
TI  - [Five adult cases of Epstein-Barr virus-associated hemophagocytic
      lymphohistiocytosis].
AB  - Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is
      more common in children, and is characterized by pancytopenia, liver dysfunction
      and coagulopathy caused by interactions between EBV-infected T cells and
      activated macrophages. We describe here five adults with EBV-HLH. The median age
      was 17 years (range 16 approximately 40). HLH developed in 4 patients within 2
      months after the primary infection, and in the other one during the reactivation.
      All patients had a high EBV viral load in peripheral blood (2 x 10(2)-3 x 10(6)
      copies/ml) and monoclonal proliferation of EBV-infected T cells. All patients
      received immunosuppressive therapy with or without etoposide, and two patients
      required plasmapheresis due to the severity. Three patients are alive in complete
      remission (follow up periods; 13, 19, 30 months), while two patients became
      refractory to chemo-immunotherapy and died despite multidrug chemotherapy. EBV
      HLH should be more widely recognized in adults in order to achieve early
      diagnosis and appropriate treatment.

PMID- 20134145
TI  - [CD5-positive B-cell prolymphocytic leukemia].
AB  - CD5 is a T-cell marker that is expressed in mature B cell malignancies and other
      B cell chronic lymphoproliferative disorders, but the biologic function of CD5 is
      unknown. We report a 68-year-old woman with B-cell prolymphocytic leukemia (B
      PLL) expressing CD5 antigen. On admission, jaundice and hepatosplenomegaly were
      noted. Hematological examination demonstrated a platelet count of 2.8 x
      10(4)/microl and a white blood cell count of 19,900/microl with 69% PLL cells.
      Surface marker analysis of the PLL cells was positive for CD5, CD19, CD20, sIgM,
      and was negative for CD23, and cyclin D1 was negative in immunostaining.

PMID- 20134146
TI  - HES1 and HES5 are dispensable for cartilage and endochondral bone formation.
AB  - Notch signalling, via its downstream mediators HES1 and HES5, regulates
      development of several different tissues. In vitro studies suggest that these
      genes are also involved in chondrogenesis and endochondral bone formation. In
      order to investigate the importance of HES1 and HES5 for these developmental
      processes, mice lacking chondrogenic expression of HES1 and HES5 were constructed
      by interbreeding HES5(-/-) mice homozygous for the floxed HES1 allele
      (HES1(flox/flox)) with COL2A1-Cre transgenic mice, creating conditional HES1;HES5
      double mutant mice. The formation of cartilage and endochondral bone was studied
      in these mice using histological and immunohistochemical stainings, including
      Alcian Blue van Gieson, Safranin-O, modified Mallory Aniline Blue, tartrate
      resistant acid phosphatase and collagen type II stainings. The mice were also
      studied using several different morphometrical analyses and the differentiation
      potential of the chondrocytes was evaluated in vitro. Unexpectedly, the
      conditional HES1;HES5 double mutant mice did not display impaired development of
      cartilage or endochondral bone. Lack of altered phenotype in the conditional
      HES1;HES5 double mutant mice can be explained either by the HES1 and HES5 genes
      not being involved in cartilage and endochondral bone development or by
      functional redundancy between the genes belonging to the family of HES genes:
      that is, disruption of one gene could be compensated for by the activity of
      another. Our results further shed light on the compensatory reserves available
      during the developing cartilage and bone.

PMID- 20134147
TI  - Comparison of arterial and venous blood gases and the effects of analysis delay
      and air contamination on arterial samples in patients with chronic obstructive
      pulmonary disease and healthy controls.
AB  - BACKGROUND: Arterial blood gases (ABGs) are often sampled incorrectly, leading to
      a 'mixed' or venous sample. Delays in analysis and air contamination are common.
      OBJECTIVES: We measured the effects of these errors in patients with chronic
      obstructive pulmonary disease (COPD) exacerbations and controls. METHODS:
      Arterial and venous samples were analyzed from 30 patients with COPD exacerbation
      and 30 controls. Venous samples were analysed immediately and arterial samples
      separated into non-air-contaminated and air-contaminated specimens and analysed
      at 0, 30, 60, 90 and 180 min. RESULTS: Mean venous pH was 7.371 and arterial pH
      was 7.407 (p < 0.0001). There was a correlation between venous and arterial pH (r
      = 0.5347, p < 0.0001). The regression equation to predict arterial pH was:
      arterial pH = 4.2289 + 0.43113 . venous pH. There were no clinically significant
      differences in arterial PO2 associated with analysis delay. A statistically
      significant decline in pH was detected at 30 min in patients with COPD
      exacerbation (p = 0.0042) and 90 min in controls (p < 0.0001). A clinically
      significant decline in pH emerged at 73 min in patients with COPD exacerbation
      and 87 min in controls. Air contamination was associated with a clinically
      significant increase in PO2 in all samples, including those that were immediately
      analyzed. CONCLUSIONS: Arterial and venous pH differ significantly. Venous pH
      cannot accurately replace arterial pH. Temporal delays in ABG analysis result in
      a significant decline in measured pH. ABGs should be analysed within 30 min. Air
      contamination leads to an immediate increase in measured PO2, indicating that air
      contaminated ABGs should be discarded.

PMID- 20134148
TI  - Prevalence of comorbidities in patients with chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with many
      comorbidities, but the percentage of COPD patients who develop comorbidities has
      not been clearly defined. OBJECTIVES: We aimed to examine the relationship
      between COPD and comorbidities using information obtained from the Health Search
      Database (HSD) owned by the Italian College of General Practitioners (SIMG),
      which stores information on about 1.5% of the total Italian population served by
      general practitioners. METHODS: We conducted a population-based retrospective
      study using information obtained from the HSD. The software system used codes all
      the diagnostic records using the 9th Revision of the International Classification
      of Diseases. RESULTS: Compared to the non-COPD people, COPD patients were at
      increased risk for cardiovascular events [ischemic heart disease (6.9% in the
      general population vs. 13.6% in COPD patients), cardiac arrhythmia (6.6% in the
      general population vs. 15.9% in COPD patients), heart failure (2.0% in the
      general population vs. 7.9% in COPD patients), and other forms of heart disease
      (10.7% in the general population vs. 23.1% in COPD patients); with a higher
      impact of COPD in the elderly]; non-psychotic mental disorders, including
      depressive disorders (29.1% in the general population vs. 41.6% in COPD patients;
      with a higher impact of COPD on women aged <75 years); diabetes mellitus (10.5%
      in the general population vs. 18.7% in COPD patients); osteoporosis (10.8% in the
      general population vs. 14.8% in COPD patients), with a higher impact of COPD on
      women aged <75 years, and malignant pulmonary neoplasms (0.4% in the general
      population vs. 1.9% in COPD patients). CONCLUSIONS: Our results indicate that
      COPD is a risk factor for these comorbid conditions.

PMID- 20134149
TI  - Nuclear and chromatin reorganization during cell senescence and aging - a mini
      review.
AB  - Genetic material in the nucleus governs mechanisms related to cell proliferation,
      differentiation, and function. Thus, senescence and aging are directly tied to
      the change of nuclear function and structure. The most important mechanisms that
      affect cell senescence are: (i) telomere shortening; (ii) environmental stress
      mediated accumulation of DNA mutations, and (iii) the intrinsically encoded
      biological clock that dictates lifespan events of any particular cell type.
      Overall, these changes lead to modification of the expression of genes that are
      responsible for: (i) organization of the nuclear structure; (ii) integrity of
      transcriptionally inactive heterochromatin, and (iii) epigenetic modification of
      chromosomes due to DNA methylation and/or histone modifications. These aging
      related nuclear alterations do not only affect somatic cells. More importantly,
      they affect stem cells, which are responsible for proper tissue rejuvenation. In
      this review, we focus on epigenetic changes in the chromatin structure and their
      impact on the biology and function of adult cells as they age. We will also
      address aging-related changes in a compartment of the most primitive pluripotent
      stem cells that were recently identified by our team and named 'very small
      embryonic/epiblast-like stem cells'.

PMID- 20134150
TI  - PGC-1alpha and myokines in the aging muscle - a mini-review.
AB  - Aging is associated with far-reaching changes in physiological functions
      resulting in morbidity and ultimately death. Age-related frailty, insecurity and
      reduced physical activity contribute to a progressive loss of muscle mass and
      function, commonly referred to as sarcopenia. Due to the increase in life
      expectancy in many countries, loss of muscle mass and its consequences gain in
      relevance for public health. At the same time, the molecular mechanisms that
      underlie sarcopenia are poorly understood and therefore, therapeutic approaches
      are limited. Interestingly though, endurance, strength and stretching exercise is
      significantly superior to all known pharmacological, nutritional and hormonal
      interventions for stabilizing, alleviating and reversing sarcopenia. Thus,
      increased knowledge about the plastic changes of skeletal muscle after physical
      activity and the signaling factors that mediate the beneficial effects of
      exercise on other organs might yield a better understanding of the disease and
      open new avenues for treatment. Here, we discuss how current discoveries about
      the peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC
      1alpha), a key exercise factor in muscle, and myokines, factors produced and
      secreted by active muscle fibers, expand our view of the pathological changes and
      the therapeutic options for sarcopenia.

PMID- 20134151
TI  - Diffuse alveolar infiltrates and macroscopic hematuria: a run-and-gun affair.

PMID- 20134152
TI  - Impact of different definitions of airflow limitation on the prevalence of
      chronic obstructive pulmonary disease in the general population.
AB  - BACKGROUND: Recent surveys report a surprisingly high prevalence of chronic
      obstructive pulmonary disease (COPD) worldwide. However, there is evidence that
      the application of a fixed ratio of forced expiratory volume in 1 s (FEV(1)) to
      forced vital capacity (FVC) may result in a relevant misclassification of airflow
      limitation. OBJECTIVES: The definition of airflow limitation does have a
      significant impact on its prevalence. METHODS: Individual values of lung volumes
      were assessed in comparison to a reference population by applying either a fixed
      ratio below 0.7 or the fifth percentile of FEV(1) in relation to FVC. Based on a
      large-scale population-based survey, reference equations for lung volumes were
      derived by quantile regression analysis based on 1,809 subjects aged 25-85 years.
      Both functional definitions were applied to calculate the prevalence of airflow
      limitation. RESULTS: The prevalence of airflow limitation was significantly
      higher when applying the fifth percentile compared to the fixed ratio of 0.7 for
      all age groups and both sexes (all 6.7 vs. 1.9%; women 6.7 vs. 1.3%; men 6.6 vs.
      2.6%). Almost 26% of the subjects with airflow limitation complained of dyspnea,
      whereas COPD had not been previously diagnosed by a physician in 87%. CONCLUSION:
      The definition of airflow limitation has a major impact on the observed
      prevalence rates.

PMID- 20134153
TI  - The substructure of the suprachiasmatic nucleus: Similarities between nocturnal
      and diurnal spiny mice.
AB  - Evolutionary transitions between nocturnal and diurnal patterns of adaptation to
      the day-night cycle must have involved fundamental changes in the neural
      mechanisms that coordinate the daily patterning of activity, but little is known
      about how these mechanisms differ. One reason is that information on these
      systems in very closely related diurnal and nocturnal species is lacking. In this
      study, we characterize the suprachiasmatic nucleus (SCN), the primary brain
      structure involved in the generation and coordination of circadian rhythms, in
      two members of the genus Acomys with very different activity patterns, Acomys
      russatus (the golden spiny mouse, diurnal) and Acomys cahirinus (the common spiny
      mouse, nocturnal). Immunohistochemical techniques were used to label cell bodies
      containing vasoactive intestinal polypeptide (VIP), vasopressin (VP), gastrin
      releasing peptide (GRP) and calbindin (CalB) in the SCN, as well as two sets of
      inputs to it, those containing serotonin (5-HT) and neuropeptide Y (NPY),
      respectively. All were present in the SCN of both species and no differences
      between them were seen. On the basis of neuronal phenotype, the SCN was organized
      into three basic regions that contained VIP-immunoreactive (-ir), CalB-ir and VP
      ir cells, in the ventral, middle and dorsal SCN, respectively. In the rostral
      SCN, GRP-ir cells were in both the VIP and the CalB cell regions, and in the
      caudal area they were distributed across a portion of each of the other three
      regions. Fibers containing NPY-ir and serotonin (5-HT)-ir were most concentrated
      in the areas containing VIP-ir and CalB-ir cells, respectively. The details of
      the spatial relationships among the labeled cells and fibers seen here are
      discussed in relation to different approaches investigators have taken to
      characterize the SCN more generally.

PMID- 20134154
TI  - Distribution of the neuronal gap junction protein Connexin36 in the spinal cord
      enlargements of developing and adult opossums, Monodelphis domestica.
AB  - We use opossums Monodelphis domestica to study the development of mammalian motor
      systems. The immature forelimbs of the newborn perform rhythmic and alternating
      movements that are likely under spinal control. The hindlimbs start moving in the
      second week. Chemical synapses are scant in the spinal enlargements of neonatal
      opossums and the presence of electrochemical synapses has not been evaluated in
      this species or in other marsupials. As a first step aiming at evaluating the
      existence of such synapses in the neonatal spinal cord, we have investigated the
      presence of the exclusively neuronal gap junction protein connexin36 (Cx36) by
      immunohistochemistry in light microscopy. At birth, Cx36 immunoreactivity is
      moderate in the presumptive gray matter in both enlargements. Thereafter, it
      decreases gradually, except in the superficial dorsal horn where it increases to
      a plateau between P10 and P20. Cx36 labeling is detected in the presumptive white
      matter at birth, but then decreases except in the dorsal part of the lateral
      funiculus, where it is dense between P10 and P20. Cx36 has become virtually
      undetectable by P52. The presence of Cx36 in the spinal enlargements of postnatal
      opossums suggests that neurons might be linked by gap junctions at a time when
      chemical synapses are only beginning to form. The greater abundance of Cx36
      observed transiently in the superficial dorsal horn suggests a stronger
      involvement of this protein in spinal sensory systems than in direct motor
      control of the limbs.

PMID- 20134155
TI  - Heparin-induced thrombocytopenia in patients with Philadelphia-negative
      myeloproliferative disorders and unusual splanchnic or cerebral vein thrombosis.
AB  - BACKGROUND: Philadelphia-negative myeloproliferative disorders (Ph-MPD) are
      common causes of unusual splanchnic or cerebral vein thrombosis, which is treated
      with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Heparin
      induced thrombocytopenia (HIT) is a dangerous potential complication of this
      therapy, but it has rarely been reported in Ph-MPD. PATIENTS AND METHODS: We
      retrospectively reviewed clinical records of 29 patients with Ph-MPD who have
      been treated with UFH or LMWH for unusual splanchnic or cerebral vein thrombosis
      (3 cerebral sinus, 6 portal and 20 hepatic vein). The goal of the study was to
      determine the occurrence of new thrombotic events during heparin therapy
      secondary to HIT (HITT). RESULTS: During heparin therapy, 5 out of the 29
      patients (17%) developed a new thrombotic episode (pulmonary embolism) with a
      high clinical probability of HIT based on the 4 T's score even though not all the
      patients developed 'true' thrombocytopenia. A diagnosis of HIT was established in
      2 patients (6.8%) through the presence of heparin-related antibodies.
      CONCLUSIONS: Ph-MPD patients on heparin warrant careful monitoring and HIT has to
      be suspected whenever platelet counts drop or a new thrombosis is detectable.

PMID- 20134156
TI  - Non-lethal bone marrow necrosis under first-line arsenic trioxide therapy in
      acute promyelocytic leukaemia.

PMID- 20134157
TI  - Higher fish consumption in pregnancy may confer protection against the harmful
      effect of prenatal exposure to fine particulate matter.
AB  - BACKGROUND/AIM: The objective of this study was to assess a hypothesized
      beneficial effect of fish consumption during the last trimester of pregnancy on
      adverse birth outcomes resulting from prenatal exposure to fine air particulate
      matter. METHODS: The cohort consisted of 481 nonsmoking women with singleton
      pregnancies, of 18-35 years of age, who gave birth at term. All recruited women
      were asked about their usual diet over the period of pregnancy. Measurements of
      particulate matter less than 2.5 mum in size (PM(2.5)) were carried out by
      personal air monitoring over 48 h during the second trimester of pregnancy. The
      effect of PM(2.5) and fish intake during gestation on the birth weight of the
      babies was estimated from multivariable linear regression models, which beside
      the main independent variables considered a set of potential confounding factors
      such as the size of the mother (height, prepregnancy weight), maternal education,
      parity, the gender of the child, gestational age and the season of birth.
      RESULTS: The study showed that the adjusted birth weight was significantly lower
      in newborns whose mothers were exposed to particulate matter greater than 46.3
      microg/m3 (beta coefficient = -97.02, p = 0.032). Regression analysis stratified
      by the level of maternal fish consumption (in tertiles) showed that the deficit
      in birth weight amounted to 133.26 g (p = 0.052) in newborns whose mothers
      reported low fish intake (<91 g/week). The birth weight deficit in newborns whose
      mothers reported medium (91-205 g/week) or higher fish intake (>205 g/week) was
      insignificant. The interaction term between PM(2.5) and fish intake levels was
      also insignificant (beta = -107,35, p = 0.215). Neither gestational age nor birth
      weight correlated with maternal fish consumption. CONCLUSIONS: The results
      suggest that a higher consumption of fish by women during pregnancy may reduce
      the risk of adverse effects of prenatal exposure to toxicants and highlight the
      fact that a full assessment of adverse birth outcomes resulting from prenatal
      exposure to ambient hazards should consider maternal nutrition during pregnancy.

PMID- 20134158
TI  - Overfeeding-induced obesity in spontaneously hypertensive rats: an animal model
      of the human metabolic syndrome.
AB  - BACKGROUND/AIMS: The metabolic syndrome (MS) has become an epidemiological
      problem in Western countries. We developed a diet-induced obese rat model that
      mimics all the symptoms of MS in humans, but whose insulin resistance,
      hyperphagia and hyperleptinemia are caused by nutrition rather than genetic
      modifications. METHODS: Spontaneously hypertensive rats (SHR) were allowed for 12
      weeks to choose between a cafeteria diet (CD, 20.3 kJ/g) and standard rat chow
      (11.7 kJ/g). Controls received rat chow. RESULTS: Body weight (BW) exceeded
      control levels when SHR were fed with CD. The increase in BW was attributed to
      enhanced energy intake. The abundance of abdominal fat as well as the plasma
      levels of leptin and triglycerides increased concomitant with glucose, insulin
      and C-peptide. This prediabetic condition was further confirmed by a markedly
      increased insulin response following glucose challenge and by impaired glucose
      utilization after insulin tolerance tests. CONCLUSION: Increases in food intake
      and BW despite hyperleptinemia indicate leptin resistance following CD feeding.
      CD-fed SHR feature leptin and insulin resistance, hypertension and obesity, thus
      mimicking the situation of MS patients. As such, our model is more suitable than
      the genetically modified rat models used to study human MS.

PMID- 20134159
TI  - Moderate or supranormal folic acid supplementation does not exert a protective
      effect for homocysteinemia and methylation markers in growing rats.
AB  - BACKGROUND/AIMS: Folic acid (FA) deficiency/supplementation effects seem to be
      dependent on age group and/or physiological status. The aim was to evaluate
      changes associated with rapid growth in relation to methionine metabolism in
      rats. METHODS: Four groups (n = 10 each) of male Sprague Dawley rats (5 weeks
      old) were on diets that varied in their FA content: 0 mg FA/kg diet (deficient),
      2 mg FA/kg diet (control), 8 mg FA/kg diet (moderate supplementation), 40 mg
      FA/kg diet (supranormal supplementation). Animals were fed ad libitum for 30
      days. Biomarkers of methionine metabolism and antioxidant status were evaluated.
      RESULTS: Serum total homocysteine concentration increased (p < 0.01) in FA
      deficient animals, with no differences between the supplemented groups. The
      hepatic 'methylation ratio' (S-adenosylmethionine/S-adenosylhomocysteine) of the
      FA content groups reached similar values, which were significantly higher
      compared to the deficient group. The brain 'methylation ratio', however, remained
      unmodified independently of FA content in the diet. FA deficiency induced hepatic
      DNA hypomethylation, and supranormal FA supplementation exerted the most
      protective effect (p < 0.01). Serum folate levels increased according to FA
      dietary level, whereas no differences were seen for vitamin B(12) and vitamin
      B(6). CONCLUSIONS: FA deficiency compromises methionine metabolism whereas
      supplementation does not show an additional positive effect compared to the
      control diet in growing animals.

PMID- 20134162
TI  - Malnutrition-inflammation score independently determined cardiovascular and
      infection risk in peritoneal dialysis patients.
AB  - BACKGROUND: The malnutrition-inflammation score (MIS) is an indicator of
      malnutrition-inflammation complex syndrome and an outcome predictor in
      maintenance hemodialysis patients. However, its utility in peritoneal dialysis
      (PD) patients and its association with the Charlson comorbidity index (CCI) have
      not yet been examined. METHODS: All chronic stable PD outpatients in the PD
      center of the National Taiwan University Hospital in January 2006 were studied
      and followed for up to 18 months. The baseline MIS and CCI at the beginning of
      the study and the dates and causes of mortality or hospitalization during the
      study period were obtained. RESULTS: A total of 141 PD patients were enrolled.
      During the study period, 8 patients died and 40 patients had at least one fatal
      or nonfatal major cardiovascular or infection event. The CCI correlated
      positively and significantly with the MIS (r = +0.344, p < 0.001). The MIS and
      CCI were both independent predictors of cardiovascular and infection events in
      the multivariate Cox proportional hazard model. For every unit increase in the
      MIS, the adjusted hazard ratio for mortality was 1.177 (95% confidence interval,
      CI, 1.050-1.320, p = 0.005). For every unit increase in the CCI, the adjusted
      hazard ratio for mortality was 1.180 (95% CI, 1.046-1.330, p = 0.007).
      CONCLUSIONS: MIS can predict fatal and nonfatal cardiovascular and infection
      events in chronic stable PD patients. The CCI, which is closely associated with
      the MIS, is an independent determinant of cardiovascular and infection events as
      well. Interventional studies are indicated to confirm the utility of the MIS in
      PD populations who undergo nutritional or anti-inflammatory treatments.

PMID- 20134163
TI  - Are electrocardiographic changes in patients with acute subarachnoid hemorrhage
      associated with takotsubo cardiomyopathy?

PMID- 20134164
TI  - Hot potatoes, million dollar coat hangers and advanced coronary surgery.

PMID- 20134165
TI  - Takotsubo cardiomyopathy as an underlying mediator of myocardial infarction with
      normal coronary arteries.
AB  - OBJECTIVE: The purpose of the present study was to describe our experience with
      myocardial infarction with normal coronary arteries (MINCA) with regards to the
      prevalence, clinical characteristics, possible underlying etiologies (including
      Takotsubo cardiomyopathy, TCM) and the short- and long-term outcomes associated
      with this condition. METHODS: We retrospectively analyzed the records of 596
      consecutive patients presenting with acute myocardial infarction over a 4-year
      period and identified 24 patients (14 female, 10 male) with angiographically
      normal coronary arteries. Demographic and clinical variables and outcomes were
      reviewed. RESULTS: Mean patient age was 59 +/- 20 years. The presumed MINCA
      mechanism was TCM in 10 patients (41.7%), probable myocarditis in 5 (20.8%),
      coronary spasm in 4 (16.7%), coronary thrombus in 3 (12.5%) and aortic dissection
      in 2 patients (8.3%). After a mean follow-up of 19 +/- 14 months, 2 patients with
      probable myocarditis had died of cardiovascular causes, 1 patient with aortic
      dissection had died due to sepsis after surgery and 1 patient with TCM had died
      of noncardiovascular causes 2 years after discharge. CONCLUSION: In this study,
      we found that MINCA occurred in 4% of patients with acute myocardial infarction
      undergoing emergent coronary angiography, with the most frequent underlying
      mechanism being TCM.

PMID- 20134166
TI  - Malignancy in Crohn's disease: incidence and clinical characteristics in Japan.
AB  - BACKGROUND/AIMS: This study investigated the occurrence of malignancies in
      Japanese patients with Crohn's disease (CD) and compared the incidence with that
      in the general population. METHODS: The medical records of 294 CD patients,
      treated between 1989 and 2009, were reviewed and the prevalence of malignancies
      was assessed. Registration of person-years at risk was calculated individually,
      from the year of CD diagnosis until the year of cancer diagnosis, death or end of
      follow-up. The observed number of cancer cases was compared with the expected
      number, calculated on the basis of the individually computed person-years at risk
      and the corresponding age- and sex-specific incidence rates in the background
      population. RESULTS: Thirteen cancers developed in 12 patients among a total of
      4,248 person-years available for analysis. There were six CRCs, two gastric
      cancers, two uterine cancers, one small bowel cancer, one biliary cancer, and one
      cancer of unknown primary site. The risk of cancer (all sites) was significantly
      increased from that of the background population; SIR 2.24 (95% CI 1.19-3.83). In
      particular, the risk of CRC significantly increased in comparison to that of the
      background population; SIR 5.80 (95% CI 2.13-12.68). CONCLUSIONS: Japanese
      patients with CD are at increased risk of cancer, particularly CRC.

PMID- 20134167
TI  - Muscle MRI in myotonic dystrophy type 1 with foot drop.
AB  - The purpose of this study was to investigate the relationship of muscle MRI
      findings and gait disturbance in myotonic dystrophy type 1 (DM1) patients.
      Thirteen patients with DM1 were evaluated by manual muscle strength test and
      muscle MRI of the lower limb. All DM1 patients presenting with foot drop showed
      high intensity signals in the tibialis anterior muscles on T1-weighted imaging (p
      < 0.001). The patients presenting with gait disturbance showed high intensity
      signals in the semimembranosus, vastus intermedius and gastrocnemius medialis
      muscles, too. Disturbance of the gastrocnemius lateralis muscles was mild in all
      DM1 patients. The patients without gait disturbance showed no abnormalities,
      especially in tibialis anterior muscles on muscle MRI. Muscle MRI is useful for
      the detection of pathological muscles in DM1 patients with gait disturbance.

PMID- 20134168
TI  - Corticospinal tract change in the unaffected hemisphere at the early stage of
      intracerebral hemorrhage: a diffusion tensor tractography study.
AB  - OBJECTIVES: Contribution by the unaffected hemisphere is one of the motor
      recovery mechanisms following stroke. We attempted to investigate changes in the
      corticospinal tract (CST) in the unaffected hemisphere at the early stage in
      patients with intracerebral hemorrhage (ICH), using diffusion tensor tractography
      (DTT). SUBJECTS AND METHODS: Fifty-three consecutive hemiparetic patients and 40
      age- and sex-matched control subjects were enrolled. DTT was performed using a
      1.5-tesla system at the early stage of ICH (7-28 days after onset). We measured
      the fiber number, fractional anisotropy and apparent diffusion coefficient of CST
      tractography in the unaffected hemisphere, and assessed the motor function of the
      affected extremities. RESULTS: The fiber number of the CST in the unaffected
      hemisphere of the patient group was higher than that of the control group (p =
      0.000). In contrast, the fractional anisotropy value was lower than that of the
      control group (p = 0.018). However, there were no significant differences in the
      apparent diffusion coefficient values between the 2 groups (p = 0.654).
      CONCLUSIONS: We demonstrated that the CST in the unaffected hemisphere was
      changed at the early stage in patients with ICH, using DTT.

PMID- 20134169
TI  - Altitudinal ranging of black-crested gibbons at Mt. Wuliang, Yunnan: effects of
      food distribution, temperature and human disturbance.
AB  - We studied the altitudinal ranging of one habituated group of black-crested
      gibbons (Nomascus concolor) at Dazhaizi, Mt. Wuliang, Yunnan, China, between
      March 2005 and April 2006. The group ranged from 1,900 to 2,680 m above sea
      level. Food distribution was the driving force behind the altitudinal ranging
      patterns of the study group. They spent 83.2% of their time ranging between 2,100
      and 2,400 m, where 75.8% of important food patches occurred. They avoided using
      the area above 2,500 m despite a lack of human disturbance there, apparently
      because there were few food resources. Temperature had a limited effect on
      seasonal altitudinal ranging but probably explained the diel altitudinal ranging
      of the group, which tended to use the lower zone in the cold morning and the
      higher zone in the warm afternoon. Grazing goats, the main disturbance, were
      limited to below 2,100 m, which was defined as the high-disturbance area (HDA).
      Gibbons spent less time in the HDA and, when ranging there, spent more time
      feeding and travelling and less time resting and singing. Human activities
      directly influenced gibbon behaviour, might cause forest degradation and create
      dispersal barriers between populations.

PMID- 20134170
TI  - Developmental origins of adult disease.
AB  - Variation in the quality or quantity of nutrients consumed during pregnancy can
      exert permanent and powerful effects upon the developing fetus. This programming
      of fetal development is emerging as a new risk factor for non-communicable
      diseases of adulthood, including coronary heart disease and the metabolic
      syndrome. Epidemiological studies show that indicators of nutritional deficit in
      pregnancy are associated with greater risk of diabetes and cardiovascular
      mortality. The study of programming in relation to disease processes has been
      advanced by the development of animal models, which have utilized both under- and
      overfeeding of specific nutrients in pregnancy. Studies of this nature support
      the nutritional programming hypothesis and provide tools with which to examine
      the mechanisms through which programming may occur. Studies of animals subject to
      undernutrition in utero generally exhibit changes in the structure of key organs,
      such as the kidney and pancreas. These effects are consistent with the concept
      that programming influences remodel the development of organs. The causal
      pathways which extend from tissue remodelling to disease processes are relatively
      well characterised. In contrast, the processes which drive disordered organ
      development are poorly understood. It is noteworthy that minor perturbation of
      maternal nutritional status can programme fetal development. It is suggested
      therefore that programming is a product of altered expression of key genes. This
      drives the tissue remodelling response and future disease risk.

PMID- 20134171
TI  - Polymorphisms in NOS3, ACE and PAI-1 genes and risk of spontaneous recurrent
      miscarriage in the Gaza Strip.
AB  - OBJECTIVE: This study was conducted to investigate the correlation between
      spontaneous recurrent miscarriage (RM) and common polymorphisms in angiotensin
      converting enzyme (ACE), plasminogen activator inhibitor 1 (PAI-1) and
      endothelium-derived nitric oxide synthase 3 (NOS3) genes among women experiencing
      RM in the Gaza Strip. METHODS: The presence of these genetic profiles was
      determined for 100 women who had had at least 3 constitutive abortions and 100
      controls without any history of abortion using molecular biological techniques.
      RESULTS: The ACE D/D polymorphism was present in 49% of the study population and
      in 54% of the controls (p = 0.479). Similarly, there was no significant
      difference detected in the distribution of polymorphisms for PAI-1, with the
      4G/4G genotype present in the study group and in controls (p = 1.00). NOS3 4a/4a
      was present in 4% of the study group and in none of the 100 controls (p = 0.123).
      In this study, we also discovered a new variant in the NOS3 gene which was named
      4c allele and was encountered in 1 patient and in 1 control subject. CONCLUSION:
      There was no significant association between ACE I/D, PAI-1 4G/5G and NOS3 4a/4b
      and the occurrence of first-trimester RM. In-depth investigation of the
      association of NOS3 4a/4a with RM is strongly recommended.

PMID- 20134172
TI  - Prevalence and correlates of major chronic illnesses among older Kuwaiti
      nationals in two governorates.
AB  - OBJECTIVE: To provide community-based information on the prevalence of diabetes,
      hypertension and heart disease and to highlight their significant correlates.
      MATERIALS AND METHODS: Data were collected in a cross-sectional household survey
      of 2,487 Kuwaiti nationals aged 50 and over in 2005/2006. A proportionately
      representative sample of 1,451 respondents from a relatively more urban area
      (Capital) and 1,036 respondents from a relatively less urban area (Ahmadi) were
      interviewed. A proxy respondent was used in 5.4% of cases. Among the 2,605
      potentially eligible persons approached, 2,487 (95.5%) participated. RESULTS:
      Doctor-diagnosed prevalences of hypertension, diabetes and heart disease in the
      two governorates were reported to be 53.4, 50.6 and 17.5%, respectively. If the
      prevalence in the two governorates is reflective of the nation, a remarkable
      increase seems to have occurred since 1996. The prevalence of each of the three
      diseases increased linearly by age among both sexes. Comorbidity of the three
      diseases increased from 3.6 to 9.4 and to 20.9% among those aged 50-59, 60-69 and
      > or =70 years, respectively. Logistic regression showed the prevalence of
      chronic illnesses to be significantly higher among persons who were older,
      retired, non-Bedouin, less educated, had higher income, were less socially
      active, were obese and had poorer exercise behavior. The prevalence of diabetes
      and heart disease was significantly lower among women than men. CONCLUSION:
      Judging from data on two governorates, the prevalence of diabetes, hypertension
      and heart disease is likely to have increased to alarmingly high levels among
      older Kuwaitis, highlighting the need for focused intervention programs in order
      to reduce morbidity and increase healthy life years.

PMID- 20134173
TI  - Influence of diabetes on the outcome of acute coronary syndrome in Kuwait.
AB  - OBJECTIVES: To describe the baseline characteristics and management of patients
      with and without diabetes mellitus (DM) hospitalized with acute myocardial
      infarction (AMI) and to assess the influence of DM on hospital outcomes and
      hospital mortality. SUBJECTS AND METHODS: We analyzed data from a 6-month
      observational study (Kuwait Acute Coronary Syndrome Registry) of unselected
      patients admitted with a diagnosis of AMI over a period of 6 months, from
      December 2003 through May 2004. RESULTS: Of 1,295 patients enrolled, 609 (47%)
      were diabetics and 686 (53%) were non-diabetics. Diabetics were more likely to
      have a past history of coronary artery disease, hypertension and left ventricular
      systolic dysfunction than non-diabetics. There was less use of beta-blockers and
      aspirin in diabetics as compared to non-diabetics (62 vs. 71% and 95.5 vs. 97.9%,
      p < 0.03, for beta-blockers and aspirin, respectively). Left ventricular failure
      and cardiogenic shock occurred more often in diabetics compared to non-diabetics
      (16 vs. 7% and 5 vs. 3%, p < 0.001, for left ventricular failure and shock,
      respectively). The mortality rate was 6% for diabetics and 2% for non-diabetics
      (p < 0.001). CONCLUSION: DM is a major health problem among the adult population
      in Kuwait, and almost half the AMI population suffer from diabetes. Diabetic
      patients had higher rates of complications, especially left ventricular failure
      and cardiogenic shock, as compared to non-diabetic patients. The in-hospital
      mortality among diabetics with AMI was almost triple that of non-diabetics. The
      results of this study highlight the need to improve adherence to evidence-based
      treatment in diabetic patients with AMI.

PMID- 20134174
TI  - Comparative analysis and interobserver variation of unenhanced computed
      tomography and intravenous urography in the diagnosis of acute flank pain.
AB  - OBJECTIVES: The purpose of this study was to compare unenhanced computed
      tomography (UECT) to intravenous urography (IVU) for detecting urinary tract
      calculi, signs of obstruction and non-renal causes in the assessment of acute
      flank pain, and in their interobserver agreement. PATIENTS AND METHODS: In this
      prospective study, carried out at a university hospital over a period of 1 year,
      36 patients (27 males and 9 females) participated. Mean age was 44 +/- 15 years
      (range: 14-73 years). The patients presented with acute flank pain and underwent
      UECT and IVU. The images were blindly evaluated by 2 experienced radiologists and
      the two techniques compared using the two-tailed McNemar's test for matched
      pairs; p values <0.05 were considered significant. RESULTS: UECT detected stones
      in 11 (30.6%) patients, while IVU found them in only 8 (22.2%). The increased
      detection by UECT was due to its ability to detect smaller stones (<6 mm). UECT
      was also found to be better than IVU in determining calculus position, in
      detecting primary or secondary signs of obstruction and in identifying non
      urinary causes of flank pain. The overall average of agreement, as indicated by
      kappa values, was 0.88 for UECT and 0.61 for IVU. CONCLUSION: UECT showed better
      detectability and interobserver agreement tan IVU, suggesting that UECT could
      replace IVU as the first imaging modality in the evaluation of acute renal colic.

PMID- 20134175
TI  - Mapping of Th1-cell epitope regions of Mycobacterium tuberculosis protein MPT64
      (Rv1980c) using synthetic peptides and T-cell lines from M. tuberculosis-infected
      healthy humans.
AB  - OBJECTIVE: To identify T helper 1 (Th1)-cell stimulating and HLA-promiscuous
      peptides of MPT64 (Rv1980c), a major secreted antigen of Mycobacterium
      tuberculosis. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs)
      were obtained from 35 healthy subjects and typed for HLA-DR molecules using
      genomic methods. To identify subjects infected with M. tuberculosis, PBMCs were
      tested in antigen-induced proliferation assays with whole cells and culture
      filtrate antigens of M. tuberculosis, M. tuberculosis-specific antigens ESAT-6
      and CFP10, and MPT64. Culture filtrate-induced T-cell lines were established in
      vitro from 12 M. tuberculosis-infected and HLA-heterogeneous healthy subjects,
      and tested with 20 overlapping synthetic peptides covering the sequence of MPT64
      in Th1-cell assays, i.e. antigen-induced proliferation and/or IFN-gamma
      secretion. In addition, T-cell lines from three HLA-heterogeneous subjects were
      tested for cytotoxic activity against peptide-pulsed antigen-presenting cells.
      RESULTS: PBMCs from 12 of 35 subjects responded to M. tuberculosis-specific
      antigens ESAT-6 and CFP10 as well as to MPT64, which suggested that they were
      infected with M. tuberculosis. Ten of twelve T-cell lines established from these
      donors responded to MPT64, and nine T-cell lines responded to 1 or more of the
      peptides of MPT64 in anti- gen-induced proliferation assays. Furthermore, 18 of
      the 20 peptides of MPT64 were recognized by the T-cell lines in 1 or more assay
      systems, and at least 5 peptides were recognized by T-cell lines from HLA-DR
      heterogeneous subjects. CONCLUSION: Th1-cell-reactive epitopes are scattered
      throughout the sequence of MPT64, and at least 5 of its peptides are presented to
      Th1-cells in a HLA-promiscuous manner.

PMID- 20134176
TI  - Is repair of incisional hernias by polypropylene mesh a safe procedure?
AB  - OBJECTIVE: The aim of our study was to evaluate the safety of the intraperitoneal
      mesh repair procedure and to assess the complications that develop after the
      procedure. SUBJECTS AND METHODS: We reviewed the records of 25 patients who
      underwent intraperitoneal mesh repair procedures. Data on age, sex, size and
      cause of the hernia, postoperative mortality, and morbidity with special
      attention to complications were obtained from the medical records. RESULTS: Of
      the 25 patients (7 males, 18 females), the original operation was cholecystectomy
      in 15 cases (60%), gynaecological surgery in 2, gastric surgery in 2, and
      umbilical hernia in 2. Incisions were midline in 20 cases (80%), transverse in 2
      and laparoscopic port sites in 3 patients. The average size of the hernia was 150
      cm(2). Local complications occurred in 4 (16%) patients. Postoperative
      complications included wound infection in 3 patients and haematoma in 1 patient.
      Postoperative hospital stay ranged from 3 to 25 days with a mean of 6 days. No
      recurrence developed during 28-month follow-up. CONCLUSION: The tension-free
      repair of incisional hernia with polypropylene mesh in intraperitoneal position
      is a safe and easy procedure with acceptable morbidity and no recurrence.

PMID- 20134177
TI  - The effect of training type on oxidative DNA damage and antioxidant capacity
      during three-dimensional space exercise.
AB  - OBJECTIVE: Orbotron training is a popular training method for fighter pilots
      because it replicates a high-acceleration environment with excessive G-force. The
      purpose of this study was to investigate the effects of 9 weeks of orbotron
      training on oxidative DNA damage and antioxidant capacity in humans during 3
      dimensional space exercise. SUBJECTS AND METHODS: The subjects comprised 15
      senior cadets from the Korea Air Force Academy who had no record of medical
      disorders and who participated in a regular exercise program (3 times per week).
      They were randomly divided into three groups consisting of 5 subjects each: a
      weight training group (21.97 +/- 1.12 years), a running training group (21.53 +/-
      0.18 years) and an orbotron training group (21.48 +/- 0.29 years). Three
      dimensional exercise tests were performed before and after training, and blood
      samples were taken to measure the concentration of plasma lactate,
      malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD) activity, and
      leukocyte DNA damage. RESULTS: Plasma lactate concentrations decreased in all
      three groups when measured after training and after 30 min of recovery compared
      to before training (p < 0.05). The concentration of plasma MDA also decreased
      after training in all blood samples compared to the values obtained before
      training although there was no significant difference in the weight training and
      orbotron training groups. In contrast, the activity of erythrocyte SOD increased
      for all three groups compared to before training (p < 0.05). In the comet assay
      results, the greatest lymphocyte DNA damage was demonstrated at the end of
      exercise compared to the other three samples under all conditions, and these
      aspects were commonly observed in all three parameters of lymphocyte DNA damage
      (tail DNA, tail length and tail moment) (p < 0.05). CONCLUSION: It can be
      concluded that the three types of exercise training reduced plasma lactate
      concentration, improved antioxidant enzyme activity, and further protected the
      body against oxidative stress (lipid peroxidation and DNA damage). Although we
      have identified an effect of exercise training on the levels of antioxidants and
      oxidants, our cohort was small, so further studies are needed to evaluate the
      different types of exercise training.

PMID- 20134178
TI  - Clinical comparison of 12 mg ropivacaine and 8 mg bupivacaine, both with 20
      microg fentanyl, in spinal anaesthesia for major orthopaedic surgery in geriatric
      patients.
AB  - OBJECTIVE: The aim of this study was to compare the haemodynamic and anaesthetic
      effects of 12 mg ropivacaine and 8 mg bupivacaine, both with 20 microg fentanyl,
      in spinal anaesthesia for major orthopaedic surgery in geriatric patients.
      SUBJECTS AND METHODS: Sixty American Society of Anesthesiologists (ASA) II-III
      patients scheduled for hip arthroplasty were randomly assigned to receive an
      intrathecal injection of either 12 mg ropivacaine with 20 microg fentanyl (group
      R, aged 70 +/- 7 years, range 67-89) or 8 mg hyperbaric bupivacaine with 20
      microg fentanyl (group B, aged 69 +/- 6 years, range 66-92). Motor and sensory
      block, haemodynamics and side effects were recorded. RESULTS: Mean levels of
      sensory block were similar, but the onset time of sensory block in group B (2.52
      +/- 0.69 min) was shorter than that in group R (3.17-0.72 min); the difference
      was statistically significant (p < 0.01), and the number of patients who had
      motor Bromage scale 3 in group B (24) was greater than in group R (16). The
      difference was also statistically significant (p < 0.05). Systolic and diastolic
      arterial pressures (SAP, DAP) and heart rate (HR) decreased after the block in
      both groups. SAP (after the 60th and 120th min of block), DAP (all measurement
      times), and HR (after the 20th, 25th and 30th min of block) were lower in group B
      than in group R. CONCLUSIONS: The data showed that 12 mg of ropivacaine and 8 mg
      of bupivacaine with 20 microg fentanyl in spinal anaesthesia can provide
      sufficient motor and sensory block for major orthopaedic surgery in geriatric
      patients. However, ropivacaine caused less motor block and haemodynamic side
      effects than bupivacaine during the procedure.

PMID- 20134179
TI  - Comparison of conventional versus colored compomers for class II restorations in
      primary molars: a 12-month clinical study.
AB  - OBJECTIVE: To evaluate the 12-month clinical performance of conventional
      (Compoglass F) and colored (Twinky Star) compomer restorative materials in class
      II restorations of primary molars. MATERIALS AND METHODS: A total of 196
      restorations were placed in 98 children aged between 5 and 10 years (mean age:
      7.43 +/- 1.31 years) who had bilateral matched pairs of carious posterior class
      II primary molars. A split-mouth design was used in which 2 materials (Compoglass
      F, Twinky Star) were randomly placed on contralateral sides by 3 dentists. At
      baseline, after 6 and after 12 months, the restorations were evaluated using
      modified US Public Health Service criteria for: secondary caries, marginal
      integrity, marginal discoloration, anatomic form and surface texture. The Alpha
      and Bravo scores were considered as clinical success. The data were subjected to
      statistical analysis by the Wilcoxon and McNemar tests (p < 0.05). The Kaplan
      Meier survival method was applied to estimate survival percentages. RESULTS: No
      significant difference was found among the groups at all recalls regarding
      marginal integrity, marginal discoloration, anatomic form, secondary caries and
      surface texture. The 12-month mean cumulative survival rate of Compoglass F was
      95.7%, while in the Twinky Star group, the survival rate was 93% in class II
      restorations with no significant difference between the groups for either
      material. CONCLUSION: Both conventional and colored compomer materials are
      suitable restorative materials for primary teeth for at least 12 months. Colored
      compomers could also be a good alternative to tooth-colored compomers in the
      restoration of primary molars.

PMID- 20134180
TI  - Cryptogenic gelastic epilepsy originating from the right temporal lobe.
AB  - OBJECTIVE: To present a case of intractable cryptogenic gelastic epilepsy with
      ictal video-EEG to localize the seizure focus. CLINICAL PRESENTATION AND
      INTERVENTION: A 39-year-old female presented with a 2-year history of intractable
      gelastic epilepsy characterized by recurrent episodes of stereotyped pathological
      laughter, transient unresponsiveness, automatisms and brief postictal confusion.
      The patient failed to respond to multiple antiepileptic drugs. Several interictal
      EEGs did not show any abnormalities. Magnetic resonance imaging of the head with
      seizure protocol and diffusion tensor imaging were normal. Ictal video-EEG
      monitoring showed rhythmic, sharp activity emanating from the right temporal
      lobe. CONCLUSION: This case suggests that the right temporal lobe may be actively
      involved in the epileptogenic network generating gelastic epilepsy. Video-EEG
      monitoring should be considered for patients with gelastic epilepsies to better
      clarify the nature of events, localize the seizure focus and correlate EEG
      changes with the clinical manifestations.

PMID- 20134181
TI  - Peripheral giant cell granuloma and peripheral ossifying fibroma in children: two
      case reports.
AB  - OBJECTIVES: The aim of this study was to present the clinical and
      histopathological evaluation of reactive gingival lesions, such as peripheral
      giant cell granuloma (PGCG) and peripheral ossifying fibroma (POF), as
      exemplified in two cases. CLINICAL PRESENTATION AND INTERVENTION: A 12- and a 13
      year-old girl were referred to the Department of Pedodontics, both complaining of
      a painless swelling mass. After histopathological evaluation, the lesions were
      diagnosed as PGCG and POF. These gingival enlargements were totally resected
      after adequate clinical and radiological examinations. No recurrence has occurred
      in the 1-year follow-up period. CONCLUSION: These cases show that without
      histopathological evaluation, these two lesions could have been misdiagnosed due
      to their similarity in appearance. Early detection and treatment of these lesions
      are important to reduce bone loss or displacement of dental germs or teeth.

PMID- 20134182
TI  - Idiopathic postpartum intussusception: a rare cause of acute abdominal pain.
AB  - OBJECTIVES: To present a case with acute abdominal pain due to idiopathic
      intestinal intussusception diagnosed by ultrasound and computed tomography (CT)
      during the early postpartum period. CLINICAL PRESENTATION AND INTERVENTION: A 21
      year-old female patient was admitted to our hospital with abdominal pain, nausea
      and emesis after a normal vaginal delivery. Laboratory tests done at admission
      were within normal limits except for leukocytosis. Physical examination revealed
      abdominal distention, guarding and rebound tenderness. Abdominal ultrasound and
      oral contrast-enhanced CT showed a complex mass in the hypogastrium, with a
      typical configuration of intussusception. Emergent laparotomy revealed ileoileal
      invagination approximately 70 cm to the ileocecal valve but no lead point. A
      partial ileal resection was performed. CONCLUSION: This case shows that when
      intussusception is suspected, an abdominal ultrasound should be performed even in
      patients with atypical symptoms. CT may be used to confirm the diagnosis.

PMID- 20134183
TI  - Is atrial fibrillation a prognosticator in acute pulmonary thromboembolism?

PMID- 20134184
TI  - Differences between newborn and adult mice in their response to immune
      thrombocytopenia.
AB  - BACKGROUND: Sick neonates frequently develop severe thrombocytopenia. OBJECTIVE
      AND METHODS: In order to test the ability of fetal mice to increase their
      megakaryocyte size and ploidy in response to thrombocytopenia, we injected an
      antiplatelet antibody (MWReg30) into pregnant mice daily for 7 days, and into
      nonpregnant adult mice to serve as controls. After that time, platelet counts
      were obtained and megakaryocytes in the bone marrow, liver, and spleen were
      stained with anti-von Willebrand factor antibody, individually measured, and
      quantified. RESULTS: Our study demonstrated that megakaryocytopoiesis in newborn
      mice shares many features of human fetal/neonatal megakaryocytopoiesis, including
      the small size of megakaryocytes. In response to thrombocytopenia, adult mice
      increased megakaryocyte volume and concentration, primarily in the spleen.
      Newborn mice, in contrast, increased the megakaryocyte concentration in the
      spleen, but exhibited no increase in megakaryocyte volume in any of the organs
      studied. In fact, the megakaryocyte mass was significantly lower in the bone
      marrow of thrombocytopenic neonates than in age-matched controls. CONCLUSIONS: We
      concluded that fetuses have a limited ability to increase their megakaryocyte
      mass in response to consumptive thrombocytopenia, compared to adult mice. These
      observations provide further evidence for the existence of biological differences
      between fetal/neonatal and adult megakaryocytopoiesis.

PMID- 20134185
TI  - Iberoamerican Congress on Neuroimmunomodulation. Preface.

PMID- 20134186
TI  - Interleukin-1 resets glucose homeostasis at central and peripheral levels:
      relevance for immunoregulation.
AB  - We briefly discuss here evidence showing that the capacity of IL-1beta to mediate
      adjustments of glucose homeostasis can be added to the already well-known
      pleiotropic effects of this cytokine. Such adjustments, which are necessary for
      satisfying the high energetic demands of immune/inflammatory responses, can be
      mediated by effects of endogenous IL-1 exerted at peripheral and brain levels in
      a concerted action with other cytokines and neuroendocrine mechanisms.

PMID- 20134187
TI  - Intrathymic T cell migration is a multivectorial process under a complex
      neuroendocrine control.
AB  - The thymus is responsible for normal T cell development, a process that includes
      cell proliferation, death, migration, and T cell receptor gene rearrangements.
      Moreover, it depends on interactions between developing thymocytes and thymic
      microenvironmental cells. Along with differentiation, thymocytes migrate and such
      oriented movement is regulated by several molecular interactions, comprising
      extracellular matrix (ECM) elements and chemokines. We postulated that
      intrathymic T cell migration is a multivectorial process; each individual vector
      being represented by a given molecular interaction. In vivo and in vitro
      experiments revealed that migration of developing thymocytes, including the
      export of mature T cells, is upregulated by hormones, such as growth hormone and
      triiodothyronine, through the modulation of ECM-mediated interactions, associated
      or not with the chemokine CXCL12. Recent data revealed that molecular
      interactions typically found in the nervous system also affect intrathymic T cell
      migration. Semaphorin-3A, a soluble member of the semaphorin family, is involved
      in the control of human thymocyte migration, bearing a chemorepulsive role. Such
      an effect is partially due to its downregulatory effect upon the interactions
      mediated by fibronectin and laminin, as well as CXCL12. These data unravel a
      complex neuroendocrine control intrathymic T cell migration, involving both
      endocrine and paracrine molecular interactions.

PMID- 20134188
TI  - Progesterone and the spinal cord: good friends in bad times.
AB  - In recent years, a growing list of publications point to the value of steroid
      hormones as an interesting option for the treatment of several type of lesions
      and diseases of the nervous system. Progesterone, well known for its role in
      pregnancy, has recently been shown to exert neuroprotective and promyelinating
      effects in both, the peripheral and central nervous system, including the injured
      spinal cord. Previous work from our laboratory has shown that progesterone
      actions in experimental models of spinal neurodegeneration or injury may involve
      the modulation of brain-derived neurotrophic factor, a neurotrophin with
      important implications in neuronal survival and axonal regeneration. The spinal
      cord is target for progesterone since neurons and glial cells express the
      intracellular receptors for this neuroactive steroid. However, the presence in
      the spinal cord of new membrane receptors and the enzymes involved in
      progesterone metabolism to its reduced derivatives, which modulate the activity
      of neurotransmitter receptors, suggest that progesterone actions involve
      pleiotropic mechanisms. Our recent data uncovering several molecular events may
      help to understand the protective and promyelinating actions of progesterone and
      further support the role of this steroid as a promising therapeutic agent for
      neurotrauma and/or neurodegenerative diseases.

PMID- 20134189
TI  - Inflammatory agents involved in septic miscarriage.
AB  - Even though the understanding of the cause of early pregnancy loss due to
      chromosomal abnormalities has improved, there is a dearth of knowledge of the
      causes of loss in euploid conceptuses. Maternal infections are a cause of abort
      in humans, but the mechanisms are not clear, so we have developed a murine model
      to study the mechanism of septic abortion by inducing embryonic resorption (ER)
      with lipopolysaccharide (LPS). We demonstrated that augmented production of
      nitric oxide (NO) and prostaglandins (PG) is involved in ER, and that inhibitors
      of their synthesis could prevent ER. Also, we observed an increase in the
      oxidative damage, evidenced by nitration of tyrosine proteins, due to the
      peroxynitrite anion. Since an association between chronic marijuana smoking and
      early miscarriage has been shown in women, we studied the participation of
      anandamide (AEA), the principal endocannabinoid, on the mechanism of action of
      LPS. We showed that LPS-induced NO synthesis and tissue damage were mediated by
      AEA, and that this endotoxin inhibited AEA degradation and increased its
      synthesis. These results suggest that several inflammatory molecules participate
      in the mechanism of early pregnancy loss and that their modulation could be
      useful tools to prevent it.

PMID- 20134190
TI  - Endocannabinoid system participates in neuroendocrine control of homeostasis.
AB  - The hypothalamo-neurohypophyseal system plays a role in homeostasis under a
      variety of stress conditions, including endotoxemia. Oxytocin (OXT) and
      vasopressin (VP) are important hormones synthesized by neurons in the
      hypothalamic paraventricular and supraoptic nuclei and released into different
      brain regions and from the neurohypophyseal terminals into the blood in response
      to many patho-physiological stimuli. However, the mechanism that controls OXT and
      VP secretion has not been fully elucidated. Nitric oxide (NO) is a known mediator
      that regulates the release of these hormones. The endocannabinoid system is a new
      intercellular system that modulates several neuroendocrine actions.
      Endocannabinoids (eCB) are released as retrograde messengers by many neurons,
      including hypothalamic magnocellular neurons and cannabinoid receptors are
      localized within these neurons, as well as in the anterior and posterior
      pituitary lobes, suggesting an eCB role in the production and release of OXT and
      VP. Lipopolysaccharide (LPS) injection is a model used as immune challenge. LPS
      causes a neuroendocrine response that is mediated by cytokines, tumor necrosis
      factor-alpha being one of them. We focused on NO and endocannabinoid system
      participation on OXT and VP production and secretion during basal and stress
      conditions and found that eCB affect basal OXT and VP secretion by acting
      differently at each level of the hypothalamo-neurohypophyseal system. After LPS,
      there is an increase in eCB synthesis that enhances OXT secretion.

PMID- 20134191
TI  - Tolerogenic dendritic cells in the control of autoimmune neuroinflammation: an
      emerging role of protein-glycan interactions.
AB  - During the past decade, a great deal of information has contributed to our
      understanding of the immunosuppressive pathways that operate during the
      resolution of autoimmune pathology, including central nervous system (CNS)
      inflammation. Activation of these pathways is accomplished through the
      integration of an intricate network of inhibitory signals and immune suppressive
      cells, including regulatory T cells, myeloid-derived suppressor cells,
      'alternatively activated' macrophages and tolerogenic dendritic cells (DCs).
      During the course of inflammatory diseases, immature or mature DCs may be
      licensed by different stimuli (e.g. cytokines, neuropeptides and growth factors)
      to become tolerogenic and suppress pathogenic T cell responses, thus emphasizing
      the outstanding plasticity of these cells. Recent findings have shed light to an
      immunoregulatory circuit by which galectin-1, an endogenous glycan-binding
      protein, favors the differentiation of regulatory DCs which promote T cell
      tolerance and contribute to resolution of autoimmune pathology through mechanisms
      involving IL-27 and IL-10. Together with the ability of galectin-1-glycan
      interactions to selectively blunt T helper (Th)1 and Th17 responses, this effect
      provides a rational explanation for the broad immunosuppressive effects of this
      glycan-binding protein in several experimental models of chronic inflammation and
      cancer. In this mini review, we will summarize the regulatory signals leading to
      the differentiation of tolerogenic DCs and their participation in CNS
      inflammation. In addition, we will underscore recent findings on the emerging
      role of galectin-glycan interactions in the establishment of immunosuppressive
      networks during the resolution of chronic inflammation.

PMID- 20134192
TI  - Keeping the balance between immune tolerance and pathogen immunity with
      endogenous neuropeptides.
AB  - Identification of the factors that regulate the immune tolerance and control the
      appearance of exacerbated inflammatory conditions is crucial for the development
      of new therapies of inflammatory and autoimmune diseases. Although much is known
      about the molecular basis of initiating signals and pro-inflammatory chemical
      mediators in inflammation, it has only recently become apparent that endogenous
      stop signals are critical at early checkpoints within the temporal events of
      inflammation. Some neuropeptides and hormones that are produced during the
      ongoing inflammatory response have emerged as endogenous anti-inflammatory agents
      that participate in the regulation of the processes that ensure self-tolerance
      and/or inflammation resolution. We will examine the latest research findings,
      which indicate that neuropeptides participate in maintaining immune tolerance in
      two distinct ways: by regulating the balance between pro-inflammatory and anti
      inflammatory factors, and by inducing the emergence of regulatory T cells with
      suppressive activity against autoreactive T cell effectors. We will also examine
      the role of some of these neuropeptides as mediators of innate defense acting as
      natural antimicrobial peptides. Both anti-inflammatory and pro-resolving
      neuropeptides have shown therapeutic potential for a variety of inflammatory and
      autoimmune disorders and could be used as biotemplates for the development of
      novel pharmacologic agents. From a physiological point of view, neuropeptides
      play a critical role in the innate-adaptive immune cross talk that allows
      survival.

PMID- 20134193
TI  - When immune-neuro-endocrine interactions are disrupted: experimentally induced
      arthritis as an example.
AB  - We studied whether, in parallel to the activity of the hypothalamus-pituitary
      adrenal axis and the sympathetic nervous system, hypothalamic cytokine expression
      and monoaminergic neurotransmitter concentrations are affected during the
      development and chronification of arthritis induced by immunization of rats with
      type II collagen. Corticosterone levels were increased only transiently, and were
      even below the normal range as the disease progressed. Increased adrenaline blood
      levels and hypothalamic IL-1beta and IL-6 overexpression were observed only
      during the induction phase of the disease. The increase in hypothalamic
      noradrenaline content during the symptomatic phase was paralleled by a gradual
      loss of sympathetic fibers in the joints. Depletion of hypothalamic noradrenergic
      neurons at this time did not affect the symptomatology. Contrary to observations
      in healthy animals, no correlation between hypothalamic IL-1beta expression and
      noradrenaline content was observed in rats with arthritis. The dissociation
      between hypothalamic cytokine gene expression and noradrenergic neuronal
      activity, the lack of sustained stimulation of the stress axes, and the loss of
      sympathetic signals in the joints indicate that the communication between
      afferent immune messages to the central nervous system and two main efferent anti
      inflammatory pathways under control of the brain are disrupted during
      experimental arthritis.

PMID- 20134194
TI  - Effects of stress on the immune response to Theiler's virus--implications for
      virus-induced autoimmunity.
AB  - Psychological stress is an important factor in susceptibility to many diseases.
      Our laboratory has been investigating the impact of stress on the susceptibility
      to Theiler's virus-induced demyelination (TVID), a mouse model of multiple
      sclerosis. Using immunodominant viral peptides specific for identification of
      either CD4(+) or CD8(+) T cells, stress reduced IFN-gamma-producing virus
      specific CD4(+) and CD8(+) T cells in the spleen and CD8(+) T cells in the CNS.
      Expression of mRNA for the Th1 transcription factor T-bet and the Th2
      transcription factor GATA-3 were decreased in spleen cells isolated from stressed
      mice. Cytokine production by cells isolated from the CNS or spleens following
      stimulation with virus indicated that stress decreased both type 1 and type 2
      responses. The adverse effects of stress were partially reversed by concurrent
      RU486 administration but mimicked by dexamethasone, indicating a major role for
      glucocorticoids. Global stress-induced immunosuppression resulted in higher
      levels of virus replication and dissemination. The higher viral load subsequently
      led to an earlier disease onset and more severe clinical and histological signs
      of demyelinating disease. Our results have important implications for
      understanding the pathogenesis of MS, and suggest that stressful events during
      early infection with an agent capable of inducing demyelination may result in
      immunosuppression and failure to eliminate the pathogen, which in turn may lead
      to the development of MS.

PMID- 20134195
TI  - Disease-modifying immunotherapy for the management of autoimmune diabetes.
AB  - Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that destroys the
      insulin-secreting beta-cells of the pancreas. It is now possible to predict those
      candidates that will progress to T1D before the full onset of the disease.
      Prevention of uncontrollable autoimmunity against beta-cells in therapies for T1D
      is mandatory to preserve the beta-cell mass. Therefore, immunomodulatory
      strategies directed to inhibiting the activity of self-reactive T cell clones as
      well as induction of regulatory T cells would be beneficial for prevention of T1D
      or recurrence of beta-cell autoimmunity against islet cell allografts.

PMID- 20134196
TI  - Differential regulation of IgG-NMO autoantibodies on S100Beta protein and
      disability in relapsing neuromyelitis optica.
AB  - Neuromyelitis optica (NMO), an uncommon central nervous system (CNS)
      demyelinating disease, produces transverse myelitis and severe optic neuritis.
      IgG-NMO autoantibody, a specific immunoglobulin binding aquaporin-4 water channel
      protein, confirms that NMO is a different entity to multiple sclerosis. Parallel
      to cytokine down-regulations found in serum of relapsing-NMO (rNMO) patients, it
      has been reported that IgG-NMO may also confer a worse course of the disease in r
      NMO Caribbean patients. In this study, we were interested in exploring the
      influence of IgG-NMO autoantibody on S100beta levels and clinical parameters from
      serum of r-NMO patients. Serum samples from 24 rNMO patients and 10 controls were
      evaluated. The reduction of S100beta observed in r-NMO patients was not
      significant compared to controls; and no differences were present regarding IgG
      NMO immunoreactivity. At the same time, a significant correlation was also
      observed between IgG-NMO autoantibody serum detection and EDSS (Expanded
      Disability Status Scale) in rNMO. These results corroborate a differential
      regulation of IgG-NMO autoantibodies on the S100beta glial marker and on the
      disability present in rNMO patients.

PMID- 20134197
TI  - Role of toll-like receptors and inflammation in adrenal gland insufficiency.
AB  - Adrenal gland insufficiency - the clinical manifestation of deficient production
      or action of adrenal steroids - is a life-threatening disorder. Among many
      factors which can predispose to primary adrenal failure, an autoimmune
      adrenalitis and infectious agents play a major role. The initial host defense
      against bacterial infections is executed primarily by the pattern recognition
      receptors, e.g. Toll-like receptors (TLRs), expressed in cells from the innate
      immune system. Upon activation, TLRs have been found to regulate various levels
      of innate and adaptive immunity as well as control tissue inflammation. TLRs are
      implicated in adrenal cell turnover and steroidogenesis during inflammation.
      Therefore, TLRs play a crucial role in the activation of adrenal inflammation
      mediating adrenal gland dysfunction during septicemia.

PMID- 20134198
TI  - A clinical correlate of the dysregulated immunoendocrine response in human
      tuberculosis.
AB  - Wasting is a prominent feature in tuberculosis (TB), but its underlying
      mechanisms are incompletely understood. Immunoendocrine disturbances may be
      linked to the consumption state of TB patients, since hormones and cytokines can
      affect energy expenditure and metabolism. To approach this possibility, we have
      determined leptin, IL-18, and adrenal steroid plasma levels and body mass index
      (BMI) in newly diagnosed patients with mild, moderate and severe pulmonary TB,
      household contacts (HHC), and healthy controls (HCO). HHC displayed higher levels
      of leptin than HCO and TB patients. TB patients showed a gradual decrease in BMI
      and leptin concentrations with increasing disease severity, whereas a positive
      correlation between this hormone and BMI was found in the HCO group. Cortisol
      concentrations tended to be higher in TB patients. DHEA levels were decreased in
      TB patients and to a lesser extent in HHC, whereas IL-18 concentration was
      significantly increased in patients with severe disease. Since HHC are known to
      cause a latent subclinical infection, it seems clear that controlled tuberculous
      infection and manifested TB disease are accompanied by a dissimilar profile of
      immunoendocrine markers.

PMID- 20134199
TI  - Immune neuroendocrine interactions during a fungal infection in immunocompetent
      or immunosuppressed hosts.
AB  - The yeast Candida albicans belongs to the microflora of healthy individuals,
      although it can infect a variety of tissues ensuing changes in the host's immune
      status. To evaluate the effect of neuroendocrine input on the early immune
      response during the fungal infection, we use a 3-day paradigm of chronic varied
      stress in Wistar rats infected with C. albicans. We find that stress mediators
      contribute to the spread of the fungus and downregulate critical functions of
      phagocytic cells at the infection site. Phenotypic and functional alterations of
      effector cells account for the decreased resistance to candidiasis and condition
      the development of the adaptive response. Stressed hosts exhibit a higher fungal
      burden in kidneys and livers associated with hyphal forms. The hepatic
      inflammatory reaction is compromised with severe steatosis, increment of
      functional enzymes, marked lipid peroxidation and hepatocyte apoptosis. Moreover,
      infection-related sickness symptoms are significantly increased by exposure to
      stress with anorexia, weight loss, lack of leptin and depletion of glycogen
      depots. Food deprivation exacerbates the liver injury. Stress mediators perturb
      the complex immune and metabolic program that operates early during fungal spread
      and promotes severe tissue damage.

PMID- 20134200
TI  - Interplay between neuroimmunoendocrine systems during post-traumatic stress
      disorder: a minireview.
AB  - Early life stress has been suggested to mediate vulnerability to affective
      disorders. Traumatic events experienced in childhood such as sexual abuse and/or
      physical neglect may lead to psychiatric diseases in adult life, including post
      traumatic stress disorder (PTSD). Previous studies have focused on adult
      traumatic events and very little is known regarding the long-term physiological
      effects of early life stress. Here, we review the complex interplay between most
      important cognitive, neuroendocrine and immunological changes reported in PTSD,
      focusing on long-term implications of childhood maltreatment. PTSD has been
      associated with significant biological changes related to impaired cognitive
      functions, attenuated hypothalamic-pituitary-adrenal (HPA) axis function
      (hypocortisolism) and activation of innate immune responses (low-grade
      inflammation).

PMID- 20134201
TI  - Neuroimmune interactions in stress.
AB  - Stress has long been recognized as a putative modulator of immunity. Several
      clinical and experimental reports point to a role of physical and psychological
      stressors on progression or resistance to disease. Nonetheless, literature in
      this field is sometimes controversial due to the wide variety of stressors
      employed and parameters of immunity analyzed. This variation should not be
      considered a consequence of methodological inaccuracy. The stress response,
      although theoretically stereotyped in nature, may lead to slightly different
      outcomes according to several modifiers. Our group has compared the effects of
      several stressors over different parameters of brain activity, behavior, immunity
      and glucocorticoid levels. These data show altogether that while increased
      turnover of noradrenaline in the hypothalamus, along with anxiety-like behaviors
      and increase in serum corticosterone are present very often, the magnitude of
      changes in immunity may vary considerably. Thus, we review data from our group
      generated over the past decade to support that effects of stressors on immunity
      and behavior highly depend on their specifics, animal model, frequency, duration,
      intensity, perception, and coping by the stressed animal.

PMID- 20134202
TI  - Chronic expression of transforming growth factor-beta enhances adult
      neurogenesis.
AB  - Neural stem cells reside in two neurogenic regions of the adult brain: the
      dentate gyrus of the hippocampus (DG) and the subventricular zone (SVZ). Their
      proliferation, differentiation, migration and survival are modulated by intrinsic
      and extrinsic signals, forming a neurogenic niche. Brain cytokines have only been
      recently regarded as possible components of this neurogenic niche. In particular,
      we have demonstrated that transforming growth factor-beta (TGF-beta) has a pro
      neurogenic effect in the DG in a model of increased neurogenesis by
      adrenalectomy. We wanted to test whether TGF-beta has a similar effect in another
      neurogenic region, namely the SVZ. To test this possibility, adult rats were
      injected with adenoviral vectors expressing TGF-beta (Ad-TGF) or beta
      galactosidase (Ad-bgal) in the SVZ and neurogenesis was evaluated 3 weeks later.
      We have observed that chronic TGF-beta expression increased neurogenesis in the
      ipsilateral hemisphere of Ad-TGF but not in Ad-bgal-treated rats compared to
      their contralateral side. In addition, an unspecific effect of the adenoviral
      vector per se could not be totally discarded. We conclude, under our experimental
      conditions, that TGF-beta could enhance adult neurogenesis in the SVZ. This data
      increase the growing evidence supporting a pro-neurogenic role of anti
      inflammatory cytokines in the adult brain.

PMID- 20134203
TI  - Neuroimmunomodulation in the pathogenesis of Alzheimer's disease.
AB  - Evidence has been cumulated on the role of microglia cells deregulation and
      alterations in their interaction patterns with brain neurons, in the pathway
      towards neurodegeneration in Alzheimer's disease (AD). After the failure of the
      amyloid hypothesis to explain AD pathogenesis, current hypotheses focus on tau
      self-polymerization into pathological oligomers and filaments as a major culprit
      for neurofibrillary degeneration. It is worth pointing out that formation of tau
      polymers is consistent with the clinical and neuropathological observations, and
      that tangles are pathognomonic of AD and related tau disorders. In this context,
      inflammatory processes play a major role in neuronal degeneration. On the basis
      of studies on microglia and neuronal cultures, together with experiments in
      animal models, and the clinical evidence, we postulated that a series of
      endogenous damage signals activate microglia cells, inducing NFkappa-beta with
      the consequent release of cytokine mediators such as TNF-alpha, IL-6 and IL
      1beta. An overexpression of these mediators may trigger signaling cascades in
      neurons leading to activation of protein kinases gsk3beta, cdk5, abl kinases,
      along with inactivation of phosphatases such as PP1, with the resulting
      hyperphosphorylation and self-aggregation of tau protein into neurotoxic
      oligomeric species.

PMID- 20134204
TI  - Evaluation of stress systems by applying noninvasive methodologies: measurements
      of neuroimmune biomarkers in the sweat, heart rate variability and salivary
      cortisol.
AB  - The two main arms of the stress system include the autonomic nervous system (ANS)
      and the hypothalamic-pituitary-adrenal (HPA) axis. These two neural stress
      systems coordinate the response of many other physiological systems to a
      stressor, including the immune and cardiovascular systems, bringing the body back
      to homeostasis. The nervous and immune systems communicate with each other in a
      bidirectional manner. In this review, we will discuss the use of noninvasive
      methods to evaluate the immune system, ANS and HPA axis. Collection of sweat and
      saliva, and measurement of heart rate variability are noninvasive methods that
      can be applied to evaluate neuroimmune interactions. Recently, we validated a new
      methodology to simultaneously evaluate a large array of neural and immune
      biomarkers in sweat, collected through cutaneous sweat patches and measured by
      recycling immunoaffinity chromatography. Noninvasive and ambulatory methodologies
      of biomarker collection can overcome several limitations intrinsic to invasive
      methods, such as reducing the stress triggered by collection itself and allowing
      a wider application to field and community-based settings. Ultimately,
      simultaneous evaluation of neural and immune systems with noninvasive techniques
      will help elucidate the underlying interactions of these systems and their role
      in disease susceptibility and progression of stress-related disorders.

PMID- 20134205
TI  - Stress in wildlife species: noninvasive monitoring of glucocorticoids.
AB  - Depression and stress are related pathologies extensively studied in humans.
      However, this relationship is not well known in animals kept in zoos and even
      less known in wild animals. In zoo animals, acute and chronic stress caused by
      difficulties in coping with stressors such as public presence and noise, among
      others, can induce the appearance of repetitive pathological behaviors such as
      stereotypies, many times associated with organic pathologies that deeply affect
      their health and welfare. In the wild, factors such as deforestation, habitat
      fragmentation, lack of food and water, and human disturbances are potential
      causes of acute and chronic stress for the resident fauna. Glucocorticoids (GC)
      have been extensively used as stress indicators in many species including humans.
      Since chase and handling of wild animals immediately raise their GC serum levels,
      noninvasive methods have been developed to assess stress without interference
      caused by sample collection. The hormones and their metabolites can be measured
      in various body fluids and excreta and detect basal feedback free hormone
      concentrations as well as the response to ACTH and handling. In order to study
      the influence of disturbing factors we have measured GC as stress indicators by
      noninvasive techniques in dolphins and felids (ocelots, jaguarundis and margays)
      and cortisol and testosterone in spider monkeys.

PMID- 20134206
TI  - Models of aging of neuroimmunomodulation: strategies for its improvement.
AB  - Communication between the nervous and the immune systems suffers impairment with
      aging, which explains the altered homeostasis and the resulting increase of
      morbidity and mortality in aged subjects. In humans, rats and specially in mice,
      we have proposed several models to study this fact. The established models of
      premature aging have been mice and humans with poor response to stress and
      anxiety versus subjects of the same chronological age without that
      characteristic, isolation, males versus females, menopausal models (in rodents
      after ovariectomy) and obesity. In all cases, the prematurely aged animals suffer
      an alteration of the nervous system (shown by behavioral tests) and
      immunosenescence as well as oxidative and inflammatory stress, which is followed
      by early mortality. In addition, in the above-mentioned models and in normal
      chronological aging, we have observed the effect of several lifestyle strategies,
      such as ingestion of adequate amounts of antioxidants, performance of moderate
      physical exercise, and different kinds of environmental enrichment, which improve
      the function of the immune cells and their redox state as well as animal
      behavior. Therefore, they retard the aging process and seem to increase the
      longevity of the individuals.

PMID- 20134207
TI  - The CXCL12/CXCR4 pair in aged human thymus.
AB  - CXCL12 is an important CXC chemokine involved in numerous biological processes.
      We had previously demonstrated the synergistic participation of CXCL12 and IL-7
      in the control of both survival and proliferation of CD34(+) human thymic
      lymphoid progenitors. On this basis, we hypothesize a presumptive role for CXCL12
      and its receptor, CXCR4, in the thymus involution. In this respect, in the
      current report we describe the expression of both molecules in the human thymus
      during aging. Our results demonstrate that, despite the profound alterations
      observed in the thymic epithelial microenvironment of aged thymuses, the
      proportions of different CD4/CD8 thymocyte subsets do not undergo significant
      variations. Remarkably, a strong CXCL12 expression was found in older thymuses,
      which appeared in the same locations as in younger thymuses: the subcapsulary and
      medullary areas. The proportions of CXCR4(+) cells, most of them belonging to the
      CD3(-) compartment, showed no important variations in the older thymuses.
      However, within the CD34(+) cell population, a significant reduction in the
      expression of CXCR4 molecules was observed.

PMID- 20134208
TI  - Asymptomatic deep venous thrombosis after deep brain stimulation for Parkinson
      disease.
AB  - BACKGROUND/AIMS: Patients with advanced Parkinson disease (PD) are at increased
      risk for asymptomatic leg deep venous thrombosis (DVT) because of severe motor
      fluctuations. Protracted immobility in the absence of antiparkinsonian therapy
      during stereotactic surgery may further increase the risk for venous thrombosis.
      Our aim was to determine the incidence of asymptomatic DVT of leg veins in PD
      patients undergoing subthalamic nucleus deep brain stimulation (STN-DBS).
      METHODS: 41 consecutive PD patients undergoing stereotactic surgery for STN-DBS
      were investigated by ultrasound compression sonography of leg veins and D-dimer
      measurement in the week preceding surgery. After surgery, D-dimer measurements
      were repeated and when the value exceeded the normal range, ultrasound
      compression sonography was repeated to confirm or exclude DVT. RESULTS: Doppler
      ultrasonographic examinations demonstrated that 2 patients (4.9%) developed
      asymptomatic DVT shortly after surgery (8.5 days) despite the fact that none of
      the 41 patients submitted to STN-DBS had DVT before surgery and that a specific
      prophylaxis was applied during surgery. CONCLUSIONS: Our data show that advanced
      PD patients are at risk for developing asymptomatic leg DVT following
      stereotactic surgery performed for STN-DBS. A strict clinical monitoring in the
      perioperative period is advisable in order to ensure early detection of DVT and
      prevent further thrombo-embolic complications.

PMID- 20134209
TI  - Pallidotomy for severe tardive jaw-opening dystonia.
AB  - Bilateral pallidotomy was performed in a schizophrenic patient with severe jaw
      opening dystonia developed after chronic neuroleptic treatment. The dystonia led
      to sustained mandibular joint dislocation, and tracheotomy was performed after
      suffocation. The jaw-opening dystonia disappeared immediately following
      pallidotomy; the tracheotomy was closed, and he regained eating and speech
      ability. Analysis of the neuronal firing of the globus pallidus revealed low
      neuronal firing rates in the internal pallidum (GPi) and an irregular burst
      pattern of the GPi cells compared to those in Parkinson's disease. These results
      suggest that pallidotomy is a treatment option for tardive jaw-opening dystonia
      and that dystonia of this type is driven by abnormal neural activities in the
      GPi.

PMID- 20134210
TI  - Intraoperative use of the Medtronic O-arm for deep brain stimulation procedures.
AB  - The purpose of this study was to analyze the feasibility and utility of 3D
      imaging to help lead positioning during a deep brain stimulation (DBS) procedure.
      A bilateral subthalamic DBS procedure was conducted in 2 patients for idiopathic
      Parkinson's disease. Subthalamic nucleus targeting was based on preoperative
      stereotactic MRI. We used the Medtronic O-arm to perform 2D-imaging control
      (frontal and lateral) as well as quick (<30 s) 3D acquisition. This allowed us to
      check the positioning of micro-macro electrodes and definite electrodes. 3D
      images were fused with postoperative CT to assess their accuracy, and with
      preoperative MRI to visualize the anatomical location of the electrodes. 3D
      imaging is a quick and safe method to ensure perioperative control of lead
      placement during DBS procedures.

PMID- 20134211
TI  - [Long-term radiographic complications following treatment of unstable
      intertrochanteric femoral fractures with the proximal femoral nail and effects on
      functional results].
AB  - OBJECTIVES: We aimed to evaluate radiographic complications occurring after
      treatment of unstable intertrochanteric hip fractures with the Proximal Femoral
      Nail (PFN) and their effect on functional results. METHODS: The study included 35
      patients (23 women, 12 men; mean age 71 years; range 62 to 111 years) who were
      treated with the PFN for unstable intertrochanteric hip fractures. According to
      the AO classification, there were 12 type AII-1, 12 AII-2, 3 AII-3, 3 AIII-1, 5
      AIII-3 fractures. The mean time to surgery was 13 days (range 5 to 32 days).
      Closed reduction was achieved in 31 patients. The patients were evaluated
      clinically (Harris hip score) and radiographically after a mean follow-up of 32.4
      months (range 26 to 52 months) and complications were recorded. RESULTS:
      Reduction was assessed as good or acceptable in all the patients. The mean tip
      apex distance was measured as 24.2 mm (range 16 to 40 mm). Complete union was
      achieved in all but two patients. The mean Harris hip score was 82.1. The results
      were excellent in 11 patients (31.4%), good in 15 patients (42.9%), fair in seven
      patients (20%), and poor in two patients (5.7%). Radiographic complications
      mainly included secondary varus displacement in nine patients (25.7%), and
      calcification at the tip of the greater trochanter in two patients (5.7%).
      Secondary varus displacement was due to cut-out of the proximal screws (n=2),
      screw loosening due to collapse of the fracture site (n=2), and reverse Z-effect
      (n=5). Clinical results were good in two patients with calcification at the tip
      of the greater trochanter. Of nine patients with secondary varus displacement,
      the results were excellent or good in six patients, fair in two patients, and
      poor in one patient. Five patients (14.3%) required a subsequent operation.
      CONCLUSION: The correct position of the osteosynthesis material and use of an
      intramedullary nail providing a stronger fixation of the proximal part may reduce
      mechanical complications following the treatment of unstable intertrochanteric
      hip fractures.

PMID- 20134212
TI  - [Total hip arthroplasty using the anterolateral minimally invasive approach].
AB  - OBJECTIVES: We evaluated the clinical and radiographic results of total hip
      arthroplasties (THA) performed with the minimally invasive anterolateral (MIA)
      and standard anterolateral (SA) approaches. METHODS: We retrospectively reviewed
      25 patients (17 women, 8 men; mean age 57.7+/-12.5 years) and 15 patients (11
      women, 4 men; mean age 68.9+/-5.5 years) who underwent THA with the SA and MIA
      approaches, respectively. The mean body mass index was 32.5+/-5.8 kg/m2 in the SA
      group and 28.7+/-2.7 kg/m2 in the MIA group. The two groups were compared with
      respect to blood loss, operation time, blood transfusions, and length of hospital
      stay. Pain was assessed with a visual analog scale (VAS), and functional results
      were assessed with the Harris hip score (HHS). The SF-36 questionnaire was
      administered pre- and postoperatively. Radiographic evaluations included femoral
      and acetabular components and signs of loosening. The mean follow-up was 25.2+/
      8.7 months in the SA group and 26.1+/-7.2 months in the MIA group. RESULTS: The
      amount of blood loss and blood transfusions were significantly reduced and length
      of hospital stay was significantly shorter in the MIA group (p<0.001). The mean
      operation time did not differ between the two groups (p>0.05). Improvements in
      the VAS and HHS scores were significantly better in the MIA group (p<0.001).
      Similarly, improvements in all the SF-36 subscales other than general health,
      mental health, and role-physical subscales were significantly greater in the MIA
      group. Radiographically, no signs of loosening and osteolysis were seen.
      Superficial or deep wound infections did not occur. CONCLUSION: Compared to the
      SA approach, the MIA approach in THA operations is associated with shorter
      hospital stay, reduced blood loss and blood transfusions, better postoperative
      pain control, and higher levels of improvements in HHS and SF-36 scores.

PMID- 20134213
TI  - [Evaluation of interlocking intramedullary nailing in distal tibial fractures and
      nonunions].
AB  - OBJECTIVES: The aim of this study was to evaluate the results of interlocking
      intramedullary nailing in the treatment of extra-articular distal tibial
      fractures and nonunions. METHODS: The study included 45 patients (mean age 42
      years; range 27 to 52 years) who were treated with interlocking intramedullary
      nailing for distal tibial fractures (n=35) and nonunions (n=10). Of 35 fractures,
      31 were closed and four were open. The fractures were AO A1 (n=27), A2 (n=6), and
      A3 (n=2). In addition, two patients had medial, and 14 patients had lateral
      malleolus fractures. A Gross-Kempf (Howmedica) nail was used in 38 patients and
      an Expert nail (Synthes) was used in seven patients. Dynamic nailing was
      performed in 22 patients and static nailing was performed in 23 patients. No
      grafting was used. The patients were assessed clinically and radiographically
      within a mean follow-up period of 37 months (range 24 to 60 months). RESULTS:
      Union was achieved in all the patients within a mean of 4.6 months (range 3 to 7
      months). Dynamization was required in three patients. The mean time to union was
      4.4 months (range 3 to 6 months) with dynamic nailing and 4.8 months (range 3 to
      7 months) with static nailing. Complications were not serious. Transient peroneal
      nerve palsy developed in one patient (2.2%). Knee pain was seen in four patients
      (8.9%) due to the protrusion of the nail and it disappeared after removal of the
      nail. Five patients (11.1%) had limitation of ankle movements in a range of 5 to
      10 degrees. None of the patients had restriction in knee motion. CONCLUSION:
      Intramedullary interlocking nailing is a reliable method of treatment for distal
      tibial fractures and nonunions, with a high rate of union and low complication
      rate.

PMID- 20134214
TI  - [Comparison of early postoperative functional activity levels of patients
      undergoing unilateral and bilateral total knee arthroplasty].
AB  - OBJECTIVES: We compared early postoperative functional activities of patients
      undergoing unilateral and bilateral total knee arthroplasty (TKA). METHODS: A
      total of 241 patients underwent bilateral (n=130; 12 men, 118 women; mean age
      67.5+/-7.6 years) or unilateral (n=111; 7 men, 104 women; mean age 66.3+/-9.0
      years) primary TKA for gonarthrosis. All the patients had indications for
      bilateral TKA and received the same rehabilitation program postoperatively.
      Functional activities and walking speed of the patients were assessed with the
      Iowa Level of Assistance Scale and Ambulation Velocity Scale, respectively,
      before surgery and on the second and sixth postoperative days and during
      discharge. In addition, knee range of motion and HSS (Hospital for Special
      Surgery) knee scores were measured. RESULTS: There were no significant
      differences between the two groups preoperatively (p>0.05). Compared to baseline,
      functional activity levels during discharge showed significant improvement in
      both groups (p<0.05), whereas improvement in walking speed was significant only
      in the unilateral TKA group (p<0.05). Comparison of postoperative functional
      activity levels favored unilateral over bilateral TKA in all instances (p<0.05).
      The two groups did not differ significantly with respect to postoperative walking
      speed, HSS knee scores, range of motion of the knee, and mean hospital stay
      (p>0.05). Complications included knee hematoma (n=2) and deep vein thrombosis
      (n=1) in the unilateral TKA group, and knee hematoma (n=1) in the bilateral TKA
      group. CONCLUSION: Postoperative physiotherapy programs should consider decreases
      in functional activities of patients undergoing bilateral TKA.

PMID- 20134215
TI  - [Evaluation of knee peak torque in athletic and sedentary children].
AB  - OBJECTIVES: We examined the influence of sex, level of activity, and pubertal
      status on knee extension (Ext) and flexion (Fl) peak torque (PT) in children
      using an allometric modeling approach. METHODS: A total of 140 students (67
      males, 73 females) aged 12/13 years were enrolled from a Hong Kong junior high
      school, whose curricula were based on physical education (n=69) or arts (n=71).
      Isokinetic concentric Ext and Fl PT of the dominant leg was assessed at 1.04
      rad/sec using a Cybex II+ dynamometer and body mass, stature, and pubertal stage
      were measured. A repeated-measures ANOVA test was performed on absolute PT data
      with muscle action (Ext and Fl) as a within-subject factor and between-subject
      factors including sex, group, and pubertal stage. To assess the effects on body
      size-adjusted PT, linear ANCOVA and log-linear ANCOVA techniques were used with
      body mass and stature taken as covariates. RESULTS: Peak torque was significantly
      greater in boys compared to girls, and in the physical education group compared
      to the arts group. When PT was adjusted for differences in body size, there was a
      greater difference in PT between girls in the two groups compared to boys, and
      there was a significant effect of pubertal stage. Allometric analysis showed that
      PT was influenced more by stature than body mass, and PT increased at a greater
      rate than body size (both p<0.01). CONCLUSION: There may be a need for a physical
      activity intervention in sedentary 12/13 year old girls. Peak torque appears to
      increase disproportionately to body size. This may result from a greater increase
      in leg muscle mass relative to body mass.

PMID- 20134216
TI  - [The effect of abductor hallucis tendon release on residual adductus deformity in
      the surgical treatment of congenital clubfoot].
AB  - OBJECTIVES: We evaluated the effect of abductor hallucis (AH) tendon release on
      residual adductus deformity in the surgical treatment of congenital clubfoot.
      METHODS: The study included 35 patients with congenital clubfoot. Thirteen
      patients (group 1, 21 feet) underwent classical complete subtalar release, while
      22 patients (group 2, 31 feet) underwent the same treatment combined with AH
      muscle release by stripping it plantarward and transecting it distally. The mean
      age was 19.4 months (range 13 to 39 months) in group 1, and 13.5 months (range 11
      to 25 months) in group 2. The mean follow-up period was 55.5 months (range 36 to
      77 months) in group 1, and 24.7 months (range 10 to 37 months) in group 2.
      Radiographic assessments were made on preoperative, early postoperative, and
      final radiographs for the anteroposterior talo-first metatarsal angle and
      calcaneocuboid relationship, and for the anteroposterior naviculometatarsal angle
      and talonavicular relationship on final radiographs. RESULTS: Both groups showed
      significant improvement in the anteroposterior talo-first metatarsal angle in the
      early postoperative period (p<0.001); however, early and late postoperative talo
      first metatarsal angle did not differ significantly both within groups and
      between groups (p>0.05). The anteroposterior naviculometatarsal angle was 95.3
      degrees in group 1, and 96.7 degrees in group 2. The anteroposterior
      naviculometatarsal angle and talonavicular subluxation were similar in the two
      groups (p>0.05). The early and late postoperative calcaneocuboid relationship
      showed significant improvement in both groups, without a significant difference
      between the groups (p>0.05). CONCLUSION: It seems that release of the AH muscle
      does not affect the incidence of postsurgical residual adduction deformity in the
      surgical treatment of congenital clubfoot.

PMID- 20134217
TI  - [Crescentic distal metatarsal osteotomy for the treatment of hallux valgus: a
      prospective, randomized, controlled study of two different fixation methods].
AB  - OBJECTIVES: This study was designed to draw attention to a distal metatarsal
      osteotomy technique, which has been somewhat overlooked for the treatment of
      hallux valgus, and to compare the clinical and radiographic results of two
      different fixation methods. METHODS: The study included 16 feet of 13 patients
      (11 women, 2 men) who were treated with crescentic distal metatarsal osteotomy
      for mild-to-moderate hallux valgus (<35 degrees ). The patients were randomized
      to two fixation methods with two cross K-wires (group 1; 7 patients, 8 feet) and
      a compressive screw (group 2; 6 patients, 8 feet). The results were evaluated
      using the AOFAS (American Orthopaedic Foot and Ankle Society) clinical rating
      scale for hallux, and a visual analog scale for pain. Radiographic measurements
      included the hallux valgus angle (HVA), first/second intermetatarsal angle (IMA),
      and distal metatarsal articular angle (DMAA), before and 12 months after surgery.
      RESULTS: There were no significant differences between the two groups with regard
      to pre- and postoperative AOFAS scores and pain scores, which showed significant
      improvements in both groups at the end of one-year follow-up (p<0.001). The HVA
      and IMA significantly decreased from 32 degrees to 19 degrees and from 12 degrees
      to 6 degrees in group 1, and from 30 degrees to 17 degrees and from 12 degrees to
      8 degrees in group 2, respectively (p<0.001). A similar improvement was also seen
      in the DMAA (p<0.001). Postoperative radiographic improvements were similar in
      both groups. One patient in group 1 underwent revision surgery with the same
      technique due to recurrence, and one patient in group 2 had delayed union.
      CONCLUSION: Crescentic distal metatarsal osteotomy may be an appropriate
      technique in the treatment of mild-to-moderate hallux valgus.

PMID- 20134218
TI  - [Comparison of the effects of two different exercise programs on pain in
      subacromial impingement syndrome].
AB  - OBJECTIVES: We compared the effects of two different exercise programs below or
      above 90 degrees on pain in subacromial impingement syndrome (SIS). METHODS:
      Thirty patients (23 females, 7 males; mean age 52 years; range 34-70) with acute
      or subacute SIS were randomly assigned to two groups, equal in number, to receive
      an exercise program below (group 1) or above (group 2) 90 degrees , respectively.
      In addition to the standard exercise program, transcutaneous electrical nerve
      stimulation, intermittent ultrasound, and cold pack were applied, and a
      nonsteroidal anti-inflammatory drug was given. Treatment lasted two weeks (10
      sessions). Pain was assessed using the Constant score, a visual analog scale
      (VAS), and face score, and psychologic state was assessed with the Beck
      Depression Inventory. Satisfaction levels of the patients and the therapist were
      measured. Assessments were made before, and 2 and 16 weeks after treatment.
      RESULTS: Both groups had significant improvements in the Constant score, VAS
      score, and face score at 2 and 16 weeks. Change in the face score between 2 and
      16 weeks was not significant in group 2. Improvements in the Beck Depression
      Inventory were significant in both groups. While patient satisfaction
      significantly increased in both groups, increase in the therapist's satisfaction
      between 2 and 16 weeks was significant only in group 1. The two groups did not
      differ with respect to changes in the Constant score, whereas VAS score at 2
      weeks and face score at 16 weeks were significantly better in group 1. The two
      groups were similar with respect to improvements in the Beck Depression Inventory
      and patient/therapist satisfaction. CONCLUSION: The exercise program below 90
      degrees (pain-free range of motion) resulted in additional improvements in VAS
      and face scores in SIS.

PMID- 20134219
TI  - [Long-term results of treatment including creation of a gutter and muscle
      transposition for chronic sclerosing osteomyelitis].
AB  - OBJECTIVES: We evaluated long-term results of treatment including creation of a
      gutter and muscle transposition in patients with chronic sclerosing osteomyelitis
      (CSO). METHODS: Between 1980 and 1996, 11 patients (5 women, 6 men; mean age 36
      years; range 17 to 69 years) with CSO were treated with creation of a gutter and
      muscle transposition. Seven patients had femoral, and four patients had tibial
      involvement. The main complaint was pain. The patients were evaluated with
      respect to complaints and radiologically (X-ray, computed tomography, and
      magnetic resonance imaging) after a mean follow-up of 12.4 years (range 6 to 24
      years). RESULTS: During the follow up period, all the patients remained symptom
      free without the need for antibiotic treatment except for one patient with tibial
      involvement, whose pain recurred after five years. The patient's complaint
      disappeared following reoperation with the same technique. Histologic examination
      of surgical biopsies showed nonspecific changes consistent with low-grade chronic
      osteomyelitis. Cultures were negative in all cases. Control radiographies showed
      no progression of sclerosis. Computed tomography showed cortical bone formation
      surrounding the transposed muscle, and magnetic resonance imaging showed fatty
      degeneration in the transposed muscle, without any signs of active osteomyelitis.
      CONCLUSION: The aim of gutter creation and muscle transposition is to increase
      blood supply to the diseased bone segment, without the need for microsurgical
      interventions and secondary reconstructive procedures. Our long-term results show
      that this technique is efficacious in patients with femoral and tibial
      involvement.

PMID- 20134220
TI  - [The effects of two different fixation methods on femoral bone tunnel enlargement
      and clinical results in anterior cruciate ligament reconstruction with hamstring
      tendon graft].
AB  - OBJECTIVES: We investigated the effects of anatomic and non-anatomic tunnel
      fixations on femoral tunnel widening and clinical results in anterior cruciate
      ligament (ACL) reconstructions. METHODS: We retrospectively evaluated 35 patients
      who underwent arthroscopic ACL reconstruction with quadrupled hamstring tendon
      graft. Fixation was performed in the tunnel using the transcondylar RigidFix pin
      (group 1) in 18 patients (mean age 32 years), and from outside the tunnel using
      the EndoButton-CL device (group 2) in 17 patients (mean age 30 years). The
      patients were assessed using the IKDC (International Knee Documentation
      Committee) and Lysholm knee scores and tunnel widening was assessed by computed
      tomography. Ligament laxity was measured bilaterally using the Rolimeter knee
      tester. The mean follow-up was 24 months (range 21 to 38 months) in group 1, and
      24.6 months (range 12 to 36 months) in group 2. RESULTS: The two groups were
      similar with respect to age and sex distribution, operated side, the size of the
      tunnel created, and follow-up period (p>0.05). Postoperative knee scores did not
      show a significant difference (p>0.05). There was marked and excessive tunnel
      enlargement in 14 patients (77.8%) in group 1, and in 15 patients (88.2%) in
      group 2, with no significant difference between the two groups (p>0.05). Ligament
      laxity exceeded 3 mm in eight patients (44.4%) in group 1, and in three patients
      (17.7%) in group 2 (p<0.001). There was no relationship between tunnel widening
      and ligament laxity (p>0.05; r=0.175 and r=-0.01 for group 1 and group 2,
      respectively). CONCLUSION: Our results suggest that differences in the
      localization of the tunnel fixation have no effect on tunnel enlargement and that
      joint laxity may be affected by biomechanical properties of fixation materials.

PMID- 20134221
TI  - [The safety of pedicle screw fixation in the thoracic spine].
AB  - OBJECTIVES: Thoracic pedicle screw fixation has many advantages over other
      methods of spinal fixation in treating various conditions. We evaluated the
      safety and efficacy of pedicle screw fixation in the thoracic spine. METHODS: We
      retrospectively reviewed 144 patients (65 males, 79 females; mean age 38 years;
      range 9 to 82 years) who underwent posterior thoracic pedicle screw
      instrumentation. A total of 827 thoracic pedicle screws were inserted to the
      thoracic spine (T1-12) by the same senior spine surgeon using the free-hand
      technique. Indications for thoracic spine surgery were deformities (n=47, 32.6%),
      metastatic or primary tumors (n=15, 10.4%), spinal infections (n=7, 4.9%),
      degenerative diseases (n=13, 9%), and spinal trauma (n=62, 43.1%). Screw
      containment was assessed by three independent reviewers on postoperative plain
      radiographs. In addition, thin-slice computed tomography scans were obtained in
      21 suspected cases (29 screws). RESULTS: Screw containment was found in 94.3%
      (780 screws). Incorrect screw placement was found in 47 screws (5.7%), including
      31 screws (3.8%) demonstrated by plain radiographs, and 16 screws (1.9%)
      demonstrated by thin-slice computed tomography scans. More than half of the
      faulty screws (n=24, 51.1%) were detected in scoliosis patients, especially on
      the concave side of the curvature (83.3%). The most frequent site of faulty screw
      placement was the T8 level (21.3%). No symptoms or complications occurred related
      to faulty screw placement. CONCLUSION: The high accuracy of thoracic pedicle
      screw placement (94.3%) using the free-hand technique suggests that pedicle screw
      fixation of the thoracic spine is safe, reliable, and useful in the treatment of
      all types of spinal diseases.

PMID- 20134222
TI  - [Bucket-handle tear of a discoid lateral meniscus in a 6-year-old girl].
AB  - A six-year-old girl was examined upon development of pain, swelling, and locking
      in her right knee after a considerable period of discomfort and popping
      sensation. She had no history of trauma. Magnetic resonance imaging showed a
      discoid lateral meniscus, filling the entire lateral plateau and exhibiting signs
      of degeneration. On arthroscopic examination, a bucket-handle tear of the discoid
      lateral meniscus was noted and the patient was treated with arthroscopic subtotal
      meniscectomy. During the first month of follow-up, the patient had a full range
      of motion and normal gait. At three years, she maintained full range of motion
      without pain, locking, or popping. Due to the likelihood of joint degeneration,
      long-term follow-up was recommended.

PMID- 20134223
TI  - [Posterior dislocation of the hip and posterior cruciate ligament avulsion in an
      8-year-old boy].
AB  - Traumatic hip dislocation is a relatively rare entity in children. Posterior
      cruciate ligament (PCL) avulsion is also very rare in children and only a few
      cases have been reported. Because of the mechanism of injury, coexistent PCL
      avulsion with posterior dislocation of the hip is frequently seen in adults. This
      coexistence, however, has not hitherto been reported in children. We present an
      eight-year-old boy with traumatic posterior dislocation of hip and PCL avulsion.
      He was brought to hospital after a car accident in which his knee hit to the
      front part of the car when he was driving a bicycle. He had limitation of motion
      in the left hip with adduction and flexion deformity and a mild swelling and
      ecchymosis on the popliteal fossa of the left knee. Pelvic X-ray showed posterior
      dislocation of the left hip. Closed reduction was performed under general
      anesthesia. Six weeks later, he presented again with a complaint of limitation of
      motion in the left knee. On a knee radiograph, an avulsed bony fragment was noted
      near the medial femoral condyle. Three-dimensional computed tomography with
      reconstruction showed avulsion of a 0.5-cm fragment from the medial femoral
      condyle. Because of delay, no surgical intervention was attempted and he received
      physical therapy for quadriceps strengthening and improvement in the range of
      motion of the knee. One month after physical therapy, he had 120 degrees of knee
      flexion with no flexion contracture. Twelve months after injury, the patient had
      a normal hip and near-full knee flexion. He had no rotary instability and was
      active in sport.

PMID- 20134224
TI  - [Modified posterior unilateral laminectomy for a complex dumbbell schwannoma of
      the thoracolumbar junction].
AB  - We report on an uncommon type of complex dumbbell schwannoma involving the
      thoracolumbar region, which was successfully managed with unilateral
      hemilaminectomy using a modified posterior approach. A 19-year-old male patient
      presented with one-year history of low back pain radiating to the lower limbs,
      limping of two month-history, and hesitancy of micturition of 15-day duration.
      Clinically, a diagnosis of conus-cauda lesion was suspected. Findings of the X
      ray and magnetic resonance imaging of the dorsolumbar spine were suggestive of a
      complex dumbbell schwannoma, extending from the lower part of the T11 level to
      the upper part of the L1 vertebrae left to the spinal cord, with extension
      through the intervertebral foramina to the paraspinal region on the left side. A
      modified posterior approach with unilateral laminectomy was used for complete
      removal of the tumor. The histological diagnosis was schwannoma. The patient had
      minimal pain postoperatively, he was mobilized on the third day without the need
      for any external support. At one year follow-up, he had normal motor and sensory
      functions in the lower limbs.

PMID- 20134225
TI  - [Comment on: Long-term results of major upper extremity replantations].

PMID- 20134226
TI  - [Letter to the editor: Comment on: Long-term results of major upper extremity
      replantations].

PMID- 20134227
TI  - A brief overview of Escherichia coli O157:H7 and its plasmid O157.
AB  - Enterohemorrhagic Escherichia coli O157:H7 is a major food-borne pathogen causing
      severe disease in humans worldwide. Healthy cattle are a reservoir of E. coli
      O157:H7 and bovine food products and fresh produce contaminated with bovine waste
      are the most common sources for disease outbreaks in the United States. E. coli
      O157:H7 also survives well in the environment. The ability to cause human
      disease, colonize the bovine gastrointestinal tract, and survive in the
      environment, requires that E. coli O157:H7 adapt to a wide variety of conditions.
      Three major virulence factors of E. coli O157:H7 have been identified including
      Shiga toxins, a pathogenicity island called the locus of enterocyte effacement,
      and an F-like plasmid, pO157. Among these virulence factors, the role of the
      pO157 is least understood. This review provides a board overview of E. coli
      O157:H7 with an emphasis on the pO157.

PMID- 20134228
TI  - Caulobacter ginsengisoli sp. nov., a novel stalked bacterium isolated from
      ginseng cultivating soil.
AB  - A Gram negative, aerobic, nonspore-forming, straight or curved rod-shaped
      bacterium, designated Gsoil 317T, was isolated from soil of a ginseng field in
      Pocheon Province (South Korea) and was characterized using a polyphasic approach.
      Cells were dimorphic, with stalk (or prostheca) and nonmotile or nonstalked and
      motile, by means of a single polar flagellum. Comparative analysis of 16S rRNA
      gene sequences revealed that strain Gsoil 317T was most closely related to
      Caulobacter mirabilis LMG 24261T (97.2%), Caulobacter fusiformis ATCC 15257T
      (97.1%), Caulobacter segnis LMG 17158T (97.0%), Caulobacter vibrioides DSM 9893T
      (96.8%), and Caulobacter henricii ATCC 15253T (96.7%). The sequence similarities
      to any other recognized species within Alphaproteobacteria were less than 96.0%.
      The detection of Q-10 as the major respiratory quinone and a fatty acid profile
      with summed feature 7 (C18:1 omega7c and/or C18:1 omega9t and/or C18:1 omega12t;
      56.6%) and C16:0 (15.9%) as the major fatty acids supported the affiliation of
      strain Gsoil 317T to the genus Caulobacter. The G+C content of the genomic DNA
      was 65.5 mol%. DNA-DNA hybridization experiments showed that the DNA-DNA
      relatedness values between strain Gsoil 317T and its closest phylogenetic
      neighbors were below 11%. On the basis of its phenotypic properties and
      phylogenetic distinctiveness, strain Gsoil 317T should be classified as
      representing a novel species in the genus Caulobacter, for which the name
      Caulobacter ginsengisoli sp. nov. is proposed. The type strain is Gsoil 317T
      (=KCTC 12788T= DSM 18695T).

PMID- 20134229
TI  - Monitoring the bacterial community dynamics in a petroleum refinery wastewater
      membrane bioreactor fed with a high phenolic load.
AB  - The phenolic compounds are a major contaminant class often found in industrial
      wastewaters and the biological treatment is an alternative tool commonly employed
      for their removal. In this sense, monitoring microbial community dynamics is
      crucial for a successful wastewater treatment. This work aimed to monitor the
      structure and activity of the bacterial community during the operation of a
      laboratory-scale continuous submerged membrane bioreactor (SMBR), using PCR and
      RT-PCR followed by Denaturing Gradient Gel Electrophoresis (DGGE) and 16S rRNA
      libraries. Multivariate analyses carried out using DGGE profiles showed
      significant changes in the total and metabolically active dominant community
      members during the 4-week treatment period, explained mainly by phenol and
      ammonium input. Gene libraries were assembled using 16S rDNA and 16S rRNA PCR
      products from the fourth week of treatment. Sequencing and phylogenetic analyses
      of clones from 16S rDNA library revealed a high diversity of taxa for the total
      bacterial community, with predominance of Thauera genus (ca. 50%). On the other
      hand, a lower diversity was found for metabolically active bacteria, which were
      mostly represented by members of Betaproteobacteria (Thauera and Comamonas),
      suggesting that these groups have a relevant role in the phenol degradation
      during the final phase of the SMBR operation.

PMID- 20134230
TI  - Unbalanced restriction impairs SOS-induced DNA repair effects.
AB  - The contribution of a type II restriction-modification system (R-M system) to
      genome integrity and cell viability was investigated. We established experimental
      conditions which enabled the achievement of hemimethylated and unmethylated
      states for the specific bases of the recognition sequences of the host's DNA. To
      achieve this, we constructed the MboII R-M system containing only one (i.e.
      M2.MboII) out of two functional MboII methyltransferases found in Moraxella
      bovis. Using the incomplete R-M system we were able to perturb the balance
      between methylation and restriction in an inducible manner. We demonstrate that
      upon the SOS-induced DNA repair in the mitomycin C treated cells, restriction
      significantly reduces cell viability. Similar results for the well-studied wild
      type EcoRI R-M system, expressed constitutively in Escherichia coli, were
      obtained. Our data provide further insights into the benefits and disadvantages
      of maintaining of a type II R-M system, highlighting its impact on host cell
      fitness.

PMID- 20134231
TI  - Method development for electrotransformation of Acidithiobacillus caldus.
AB  - Acidithiobacillus caldus is an acidophilic, chemoautotrophic bacterium, plays
      important role in bioleaching. Gene transformation into A. caldus is difficult
      and only the conjugation method was reported successful, which method was
      relatively sophisticated. In this research, electrotransformation of A. caldus
      species was achieved for the first time using A. caldus Y-3 and plasmid pJRD215.
      Transformants were confirmed by colony PCR specific to the str gene on pJRD215,
      and the recovery of the plasmid from the presumptive transformants. Optimizations
      were made and the transformation efficiency was increased from 0.8 to 3.6 x 104
      transfomants/microng plasmid DNA. The developed electrotransformation method was
      convenient in introducing foreign genes into A. caldus.

PMID- 20134232
TI  - Efficient and precise construction of markerless manipulations in the Bacillus
      subtilis genome.
AB  - We have developed an efficient and precise method for genome manipulations in
      Bacillus subtilis that allows rapid alteration of gene sequence or multiple gene
      sequences without altering the chromosome in any other way. In our approach, the
      Escherichia coli toxin gene mazF, which was used as a counter-selectable marker,
      was placed under the control of a xylose-inducible expression system and
      associated with an antibiotic-resistance gene to create a mazF-cassette'. A
      polymerase chain reaction (PCR)-generated fragment, consisting of two homology
      regions joined to the mazF-cassette, was integrated into the chromosome at the
      target locus by homologous recombination, using positive selection for antibiotic
      resistance. Then, the excision of the mazF-cassette from the chromosome by a
      single-crossover event between two short directly-repeated (DR) sequences,
      included in the design of the PCR products, was achieved by counter-selection of
      mazF. We used this method efficiently and precisely to deliver a point mutation,
      to inactivate a specific gene, to delete a large genomic region, and to generate
      the in-frame deletion with minimal polar effects in the same background.

PMID- 20134233
TI  - HpaXm from Xanthomonas citri subsp. malvacearum is a novel harpin with two
      heptads for hypersensitive response.
AB  - A novel harpin-like protein, HpaXm, was described from cotton leaf blight
      bacteria, Xanthomonas. citri subsp. malvacearum. The hpaXm was found to be
      localized between hrp2 and hrcC. A phylogenetic analysis of the complete amino
      acid sequence or solely the 13 highly conserved residues H2N-SEKQLDQLLTQLI-COOH
      in the N-terminal alpha-helix indicates that HpaXm is evolutionarily closer to
      HpaGXag and HpaXac than to Hpa1Xoo and Hpa1Xoc. A synthesized peptide containing
      two heptads, 39-LDQLLTQ-LIMALLQ-52, from the N-terminal alpha-helical region of
      HpaXm displayed a comparable activity in inducing HR, but other two synthesized
      derivatives, HpaXmDeltaT44C and HpaXmDeltaM48Q showed a reduced activity of HR.
      The data from a GST trap test revealed that HpaXm was released into the
      extracellular medium, hpaXm mutant deficient for the leader peptide (1
      MNSLNTQIGANSSFL-15) was unable to be secreted outside cells but still induced HR
      in tobacco leaves.

PMID- 20134234
TI  - Comparative study of the nucleotide bias between the novel H1N1 and H5N1 subtypes
      of influenza A viruses using bioinformatics techniques.
AB  - Novel influenza A (H1N1) is a newly emerged flu virus which was first detected in
      April, 2009. Unlike the avian influenza (H5N1), this virus has been known to be
      able to spread from human to human directly. Although it is uncertain that how
      severe this novel H1N1 virus will be in terms of human illness, illness may be
      more widespread because most people will not have immunity to it. In this study,
      we compared the codon usage bias between the novel H1N1 influenza A viruses and
      other viruses such as H1N1 and H5N1 subtypes to investigate the genomic patterns
      of novel influenza A (H1N1). Totally 1,675 nucleotide sequences of the
      hemagglutinin (HA) and neuraminidase (NA) genes of influenza A virus including
      H1N1 and H5N1 subtypes occurred from 2004 to 2009 were used. As a result, we
      found that the novel H1N1 influenza A viruses showed the most close correlations
      with the swine-origin H1N1 subtypes than other H1N1 viruses in the result from
      not only the analysis of nucleotide compositions, but also the phylogenetic
      analysis. Although the genetic sequences of novel H1N1 subtypes were not exactly
      same as the other H1N1 subtypes, the HA and NA genes of novel H1N1s showed very
      similar codon usage patterns with other H1N1 subtypes, especially with the swine
      origin H1N1 influenza A viruses. Our findings strongly suggested that those novel
      H1N1 viruses seemed to be originated from the swine-host H1N1 viruses in terms of
      the codon usage patterns.

PMID- 20134235
TI  - Real-time PCR analysis of metabolic pathway of PHB in Acidiphilium cryptum DX1-1.
AB  - The time, yield and related genes expression of PHB accumulation of Acidiphilium
      cryptum DX1-1 were investigated under four different initial C/N ratios 1.2, 2.4,
      7.5, and 24. The results of time and yield of PHB accumulation show that the
      initial C/N ratio 2.4 was optimum for strain DX1-1 to accumulate PHB, both higher
      and lower initial C/N ratios did not favor that process. Based on the genome of
      Acidiphilium cryptum JF-5, 13 PHB accumulation related genes in strain JF-5 were
      chosen and successfully cloned from strain DX1-1. The differential expression of
      the 13 functional genes, in different C/N ratios as cited above, was then studied
      by Real-time PCR. The results show that all the 13 genes were most upregulated
      when initial C/N ratio was 2.4, and among which the gene Acry_3030 encoding poly
      beta-hydroxybutyrate polymerase and Acry_0626 encoding acetyl-CoA synthetase were
      much more upregulated than the other genes, which prove that they play the most
      important role for PHB accumulation and acetate is the main initial substance for
      PHB accumulation for strain DX1-1. Potential regulatory motifs analysis shows
      that the genes related to PHB accumulation are regulated by different promoters
      and that the motif had weak similarity to the model promoters, suggesting that
      PHB- metabolism in Acidiphilium cryptum may be mediated by a different mechanism.

PMID- 20134236
TI  - Secondary metabolites of Volvariella bombycina and their inhibitory effects on
      melanogenesis.
AB  - Four compounds were isolated from the broth culture of Volvariella bombycina and
      they were identified as ergosta-4,6,8(14),22-tetraene-3-one (1), ergosterol
      peroxide (2), indole-3-carboxaldehyde (3) and indazole (4) by interpretation of
      spectroscopic data. Among them, compound 2 exhibited melanogenesis inhibitory
      effect in cultured B16 mouse melanoma cells.

PMID- 20134237
TI  - Evaluation of the antibacterial activity of rhapontigenin produced from rhapontin
      by biotransformation against Propionibacterium acnes.
AB  - Biotransformation is often used to improve chemical activity. We evaluated the
      antimicrobial activity of rhapontigenin, converted from rhapontin after treatment
      with Pectinex. Rhapontigenin showed 4-16 times higher antimicrobial activity than
      rhapontin. Activity was higher against Gram positive strains than Gram negative
      strains. Minimum inhibitory concentrations (MICs) of rhapontigenin, retinol, and
      five antibiotics were determined by microbroth dilution method for antibiotic
      sensitive and -resistant Propionibacterium acnes. We also investigated the in
      vitro antibacterial activity of rhapontigenin in combination with antibiotic
      against antibiotic-resistant P. acnes. The antibiotic combination effect against
      resistant P. acnes was studied by checkerboard method. The combination
      formulations (rhapontigenin and clindamycin, retinol and clindamycin) showed
      synergic effects on the inhibition of the growth of clindamycin-resistant P.
      acnes. It is predictable that the combination of antibiotics with rhapontigenin
      is helpful to treat acne caused by antibiotic resistant P. acnes. The
      antibacterial activity of rhapontigenin was enhanced by biotransformation.

PMID- 20134238
TI  - A novel selenium and copper-containing peptide with both superoxide dismutase and
      glutathione peroxidase activities.
AB  - Superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) play
      crucial roles in balancing the production and decomposition of reactive oxygen
      species (ROS) in living organisms. These enzymes act cooperatively and
      synergistically to scavenge ROS. In order to imitate the synergism of these
      enzymes, we designed and synthesized a novel 32-mer peptide (32P) on the basis of
      the previous 15-mer peptide with GPX activity and a 17-mer peptide with SOD
      activity. Upon the selenation and chelation of copper, the 32-mer peptide is
      converted to a new Se- and Cu-containing 32-mer peptide (Se-Cu-32P) and displays
      both SOD and GPX activities and its kinetics was studied. Moreover, the novel
      peptide was demonstrated to be able to better protect vero cells from the injury
      induced by xanthine oxidase (XOD)/xanthine/Fe2+ damage system than its parents.
      Thus, this bifunctional enzyme imitated the synergism of SOD and GPX and could be
      a better candidate of therapeutic medicine.

PMID- 20134239
TI  - Improvement of ethanol production by electrochemical redox coupling of Zymomonas
      mobilis and Saccharomyces cerevisiae.
AB  - Zymomonas mobilis was immobilized in a modified graphite felt cathode with
      neutral red (NR-graphite cathode) and Saccharomyces cerevisiae was cultivated on
      a platinum plate anode to electrochemically activate ethanol fermentation.
      Electrochemical redox reaction was induced by 3 approximately 4 volt of electric
      potential charged to a cathode and an anode. Z. mobilis produced 1.3
      approximately 1.5 M of ethanol in the cathode compartment and S. cerevisiae did
      1.7 approximately 1.9 M in the anode compartment for 96 hr. The ethanol
      production by Z. mobilis immobilized in the NR-graphite cathode and S. cerevisiae
      cultivated on the platinum plate was 1.5 approximately 1.6 times higher than
      those cultivated in the conventional condition. The electrochemical oxidation
      potential greatly inhibited ethanol fermentation of Z. mobilis but did not S.
      cerevisiae. Total soluble protein pattern of Z. mobilis cultivated in the
      electrochemical oxidation condition was getting simplified in proportion to
      potential intensity based on SDS-PAGE pattern; however the SDS-PAGE pattern of
      protein extracted from S. cerevisiae cultivated in both oxidation and reduction
      condition was not changed. When Z. mobilis culture incubated in the cathode
      compartment for 24 hr was transferred to S. cerevisiae culture in the anode
      compartment, 0.8 approximately 0.9 M of ethanol was additionally produced by S.
      cerevisiae for another 24 hr. Conclusively, total 2.0 approximately 2.1 M of
      ethanol was produced by the electrochemical redox coupling of Z. mobilis and S.
      cerevisiae for 48 hr.

PMID- 20134240
TI  - Enhancement of L-lactic acid production in Lactobacillus casei from Jerusalem
      artichoke tubers by kinetic optimization and citrate metabolism.
AB  - Efficient L-lactic acid production from Jerusalem artichoke tubers by
      Lactobacillus casei G-02 using simultaneous saccharification and fermentation
      (SSF) in fed-batch culture is demonstrated. The kinetic analysis in the SSF
      signified that the inulinase activity was subjected to product inhibition, while
      the fermentation activity of G-02 was subjected to substrate inhibition. It was
      also found that the intracellularly NOX activity was enhanced by the citrate
      metabolism, which increased the carbon flux of Embden-Meyerhof-Parnas (EMP)
      pathway dramatically, and resulted more ATP production. As a result, when the SSF
      was carried out at 40 degrees after the initial hydrolysis of 1 h with
      supplemented sodium citrate of 10g/L, L-lactic acid concentration of 141.5 g/L
      was obtained in 30 h with a volumetric productivity of 4.7 g/L/h. The conversion
      efficiency and product yield were 93.6% of the theoretical lactic acid yield and
      52.4 g lactic acid/100 g Jerusalem artichoke flour, respectively. Such a high
      concentration of lactic acid with high productivity from Jerusalem artichoke has
      not been reported previously, and hence G-02 could be a potential candidate for
      economical production of L-lactic acid from Jerusalem artichoke at a commercial
      scale.

PMID- 20134241
TI  - Immobilization of Lactobacillus salivarius ATCC 11741 on loofa sponge coated with
      chitosan for lactic acid fermentation.
AB  - Lactic acid (LA) fermentation by Lactobacillus salivarius ATCC 11741 immobilized
      on loofa sponge (LS) was evaluated. To increase the surface area of LS for cell
      immobilization, H2O2 and chitosan were introduced as surface modifying reagents.
      Four chitosan of different molecular weight were separately coated on LS. All
      experiments were conducted in shaking flask mode at 100 rpm rotating speed and 37
      degrees with 5% CaCO3 as a pH regulating agent. The effects of initial glucose
      concentration were investigated in the range of 20-100 g L-1 on LA fermentation
      by free cells. The results indicate that the maximum concentration of LA was
      produced with 50 g L-1 glucose concentration. The immobilized cell system
      produced 1.5 times higher concentration than free cells for 24 h of fermentation.
      Moreover, immobilized cells can shorten the fermentation time by 2 fold compared
      with free cells at the same level of LA concentration. At 1% w/v chitosan in 2%
      v/v acetic acid, Yp/s and productivities of various molecular weight of chitosan
      were insignificantly different. Repeated batch fermentations showed 5 effective
      recycles with Yp/s and productivity in the range of 0.55-0.85 and 0.90-1.20 g L-1
      h-1, respectively. It is evident that immobilization of L. salivarius onto LS
      permits reuse of the system under these fermentation conditions. Scanning
      electron micrographs indicated that there were more intact cells on the chitosan
      treated LS than on the untreated LS, thus confirming the effectiveness of the LS
      chitosan combination when being utilized as a promising immobilization carrier
      for LA fermentation.

PMID- 20134242
TI  - Conversion of shrimp shell by using Serratia sp. TKU017 fermentation for the
      production of enzymes and antioxidants.
AB  - A chitinase (CHT), and a protease (PRO) were purified from the culture
      supernatant of Serratia sp. TKU017 with shrimp shell as the sole carbon/nitrogen
      source. The molecular masses of CHT and PRO determined by SDS-PAGE were
      approximately 65 kDa and 53 kDa, respectively. CHT was inhibited by Mn2+, Cu2+
      and PRO was inhibited by most tested divalent metals, EDTA. The optimum pH,
      optimum temperature, pH stability, and thermal stability of CHT and PRO were (pH
      5, 50 degrees , pH 5 degrees ) and (pH 9, 40 degrees , pH 5 degrees ),
      respectively. PRO retained 95% of its protease activity in the presence of 0.5 mM
      SDS. The result demonstrates that PRO is SDS-resistant protease and probably has
      a rigid structure. The 4th day supernatant showed the strongest antioxidant
      activity (70%, DPPH scavenging ability) and the highest total phenolic content
      (196+/-6.2 microng of gallic acid equival/mL). Significant associations between
      the antioxidant potency and the total phenolic content, as well as between the
      antioxidant potency and free amino groups, were found for the supernatant. With
      this method, we have shown that shrimp shell wastes can be utilized and it's
      effective in the production of enzymes and antioxidants, facilitating its
      potential use in industrial applications and functional foods.

PMID- 20134243
TI  - Enhancement of ornithine production in proline-supplemented Corynebacterium
      glutamicum by ornithine cyclodeaminase.
AB  - In this study, Corynebacterium glutamicum and its derived mutants were used to
      demonstrate the relationship between proline, glutamate and ornithine. The
      maximum ornithine production was shown in the culture medium (3295.0 mg/l) when
      the cells were cultured with 20 mM proline and was 15.5 times higher than in the
      presence of 1 mM proline. However, glutamate, which known as an intermediate in
      the process of converting proline to ornithine, did not have any positive effect
      on ornithine production. This suggests that the conversion of proline to
      ornithine through glutamate, is not possible in C. glutamicum. Comparative
      analysis between the wild-type strain, SJC8043 (argF-, argR-) and SJC8064 (argF-,
      argR- and ocd-), showed that C. glutamicum could regulate ornithine production by
      ornithine cyclodeaminase (Ocd) under proline-supplemented conditions. Therefore,
      proline directly caused an increase in the endogenous level of ornithine by Ocd,
      which would be a primary metabolite in the ornithine biosynthesis pathway.

PMID- 20134244
TI  - Heterologous production of streptokinase as a secretory form in Streptomyces
      lividans and nonsecretory form in Escherichia coli.
AB  - The skc gene encoding streptokinase (SK), with a molecular weight of
      approximately 47.4 kDa, was cloned from Streptococcus eouisimilis ATCC9542 and
      heterologously overexpressed in Streptomyces lividans TK24 and E. coli using
      various strong promoters. When the sprT promoter was used in the S. lividans TK24
      host, the SK protein corresponding to 47.4 kDa was detected with a smaller
      hydrolyzed protein (44 kDa), implying posttranslational hydrolysis occurred as
      reported in other expression systems. Casein/plasminogen plate assay revealed
      that plasmid construct with the signal peptide of SK was superior to that with
      the signal peptide of sprT in SK production. The maximum productivity of SK was
      calculated as less than 0.25 unit/ml of the culture broth, which was similar
      level to those from other expression systems hiring ermE and tipA promoters in
      the same host. When the skc gene was expressed in E. coli BL21(DE3)pLys under
      control of T7 promoter, relatively large amount of SK was expressed in soluble
      form without hydrolyzed protein. The SK activity produced by E. coli/pET28a
      T7pSKm was more than 2 units/ml of culture even though about half of the
      expressed protein formed inactive inclusion body.

PMID- 20134245
TI  - Production of biosurfactant lipopeptides Iturin A, fengycin and surfactin A from
      Bacillus subtilis CMB32 for control of Colletotrichum gloeosporioides.
AB  - A bacterial strain isolated from soil for its potential to control the
      anthracnose disease caused by Colletotrichum gloeosporioides was identified as a
      Bacillus subtilis. Bacillus subtilis CMB32 produced antifungal agents on M9 broth
      at 30degreesC. Biosurfactant lipopeptides produced by Bacillus subtilis CMB32
      were precipitated by adjusting to pH 2 and extracting using chloroform/methanol,
      and then were purified using column chromatography and reverse-phase HPLC.
      Molecular masses of the lipopeptides were estimated by MALDI-TOF mass
      spectrometry as (a) 1080, (b) 1486, and (c) 1044 Da, respectively. They had
      cyclic structures and amino acid compositions of (a) Pro, Asx, Ser, Tyr, Glx, (b)
      Glx, Tyr, Thr, Ala, Pro, Ile, and (c) Glx, Leu, Val, Asx, respectively. Further
      analysis revealed that Bacillus subtilis CMB32 produced three antifungal
      lipopeptides: (a) iturin A, (b) fengycin, and (c) surfactin A.

PMID- 20134246
TI  - Enhancement of clavulanic acid production by expressing regulatory genes in gap
      gene deletion mutant of Streptomyces clavuligerus NRRL3585.
AB  - Streptomyces clavuligerus NRRL3585 produces a clinically important ss-lactamase
      inhibitor, clavulanic acid (CA). In order to increase the production of CA, the
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was deleted in S.
      clavuligerus NRRL3585 to overcome the limited glyceraldehyde-3-phosphate pool;
      the replicative and integrative expressions of ccaR (specific regulator of the CA
      biosynthetic operon) and claR (Lys-type transcriptional activator) genes were
      transformed together into deleted mutant to improve clavulanic acid production.
      We constructed two recombinant plasmids to enhance the production of CA in the
      gap1 deletion mutant of S. clavuligerus NRRL3585: pHN11 was constructed for
      overexpression of ccaR-claR, whereas pHN12 was constructed for their chromosomal
      integration. Both pHN11 and pHN12 transformants enhanced the production of CA by
      2.59-fold and 5.85-fold, respectively, compared to the gap1 deletion mutant. For
      further enhancement of CA, we fed the pHN11 and pHN12 transformants ornithine and
      glycerol. Compared to the gap1 deletion mutant, ornithine increased CA production
      by 3.24- and 6.51-fold in the pHN11 and pHN12 transformants, respectively,
      glycerol increased CA by 2.96- and 6.21-fold, respectively, and ornithine and
      glycerol together increased CA by 3.72- and 7.02-fold, respectively.

PMID- 20134247
TI  - Bacteriocinogenic potential of newly isolated strains of Enterococcus faecium and
      Enterococcus faecalis from dairy products of Pakistan.
AB  - Present study was carried for the isolation of bacteriocin producing Enterococci
      from indigenous sources. Gram positive enterococci are known for having the
      ability to produce enterocins with good antimicrobial potential. A total of 34
      strains were isolated from processed dairy products of Pakistan and seven out of
      them were found to be member of genus enterococci on selective enumeration.
      Biochemical and molecular characterization revealed that four of these isolates
      (IJ-03, IJ-07, IJ-11 and IJ-12) were Enterococcus faecalis while three (IJ-06, IJ
      21 and IJ-31) were Enterococcus faecium. Local processed cheese was the source of
      all enterococcal isolates, except E. faecium IJ-21 and IJ-31 which were isolated
      from indigenous yoghurt and butter samples respectively. Bacterial isolates were
      sensitive to commonly used antibiotics except methicillin and kanamycin. They
      also lack critical virulence determinants mainly cytolysin (cyl), gelatinase
      (gel), enterococcal surface protein (esp) and vancomycin resistance (vanA and
      vanB). Polymerase chain reaction amplification identified that enterocin A and P
      genes were present in the genome of E. faecium IJ-06 and IJ-21 while E. faecium
      IJ-31 genome showed only enterocin P genes. No amplification was observed for
      genes that corresponded with the enterocins 31, AS-48, L50A, L50B and ent 1071A
      and 1071 B. Also there were no signals of amplification found for E. faecalis IJ
      11 indicating that the antimicrobial activity was because of an enterocin
      different from those checked by PCR. So the indigenous bacterial isolates have
      great potential for bacteriocin production and they had antibacterial activity
      against a variety of closely related species.

PMID- 20134248
TI  - Assessment of potential probiotic- and starter properties of Pediococcus spp.
      isolated from Turkish-type fermented sausages (sucuk).
AB  - In this study, the metabolic activities of five strains of amount of Pediococcus
      spp. in terms of the quantities they produced of lactic acid, hydrogen peroxide,
      exopolysaccharides and proteolytic activity were determined. Lactic acid levels
      produced by these strains were found to be in the range of 2.5-5.6 mg/ml. All
      strains produced hydrogen peroxide. The P. pentosaceus Z13P strain produced the
      maximum amount (0.25 mg/ml) of proteolytic activity. Exopolysaccharide (EPS)
      production by the Pediococcus strains during growth in MRS medium was in the
      range 25-64 mg/l. The susceptibility of 10 different antibiotics against these
      strains was also tested. All strains were found to be resistant to amoxicillin,
      gentamicin, and vancomicin. Antimicrobial effects of the Pediococcus on pathogens
      were also determined by an agar diffusion method. All of the strains were able to
      inhibit L. monocytogenes. The tolerance of the strains to low pH, their
      resistance to bile salts of strains, and their abilities to autoaggregate and
      coaggregate with L. monocytogenes were also evaluated.

PMID- 20134249
TI  - Structure and diversity of arsenic resistant bacteria in an old tin mine area of
      Thailand.
AB  - The microbial community structure in Thailand soils contaminated with low and
      high levels of arsenic was determined by denaturing gradient gel electrophoresis
      (DGGE). Band pattern analysis indicated that the bacterial community was not
      significantly different in the two soils. Phylogenetic analysis obtained by
      excising and sequencing six bands indicated that the soils were dominated by
      Arthobacter koreensis and proteobacteria. Two hundred and sixty-two bacterial
      isolates were obtained from arsenic contaminated soils. The majority of the As
      resistant isolates were gram-negative bacteria. MIC studies indicated that all of
      the tested bacteria had greater resistance to arsenate than arsenite. Some
      strains were capable of growing in medium containing up to 1,500 mg/l arsenite
      and arsenate. Correlations analysis of resistance patterns of arsenite resistance
      indicated that the isolated bacteria could be categorized into 13 groups, with a
      maximum similarity value of 100%. All strains were also evaluated for resistance
      to eight antibiotics. The antibiotic resistance patterns divided the strains into
      100 unique groups, indicating that the strains were very diverse. Isolates from
      each antibiotic resistance group were characterized in more detail by using the
      repetitive extragenic palindromic-PCR (rep-PCR) DNA fingerprinting technique with
      ERIC primers. PCR products were analyzed by agarose gel electrophoresis. The
      genetic relatedness of 100 bacterial fingerprints, determined by using Pearson
      product moment similarity coefficient, showed that the isolates could be divided
      into four clusters, with similarity values ranging from 5-99%. While many
      isolates were genetically diverse, others were clonal in nature Additionally, the
      arsenic-resistant isolates were examined for the presence of arsenic resistance
      (ars) genes by using PCR, and 30% of the isolates were found to carry an arsenate
      reductase encoded by the arsC gene.

PMID- 20134250
TI  - Anaerobic lipid degradation through acidification and methanization.
AB  - In biological wastewater treatment high lipid concentration is known to inhibit
      microorganisms and cause active biomass flotation. To reduce lipid inhibition, a
      two-phase anaerobic system, consisting of an anaerobic sequencing batch reactor
      (ASBR) and an upflow anaerobic sludge blanket (UASB) reactor, was applied to
      synthetic dairy wastewater. During 153 days of operation, the two-phase system
      showed stable performance in lipid degradation. In the ASBR, a 13% lipid removal
      efficiency and 10% double bond removal efficiency were maintained. In the UASB,
      the chemical oxygen demand (COD), lipid and volatile fatty acid (VFA) removal
      efficiencies were more than 80%, 70% and 95%, respectively, up to organic loading
      rate 6.5 g COD/L/day. There were no operational problems such as serious scum
      formation or sludge washout. Protein degradation occurred prior to degradation
      during acidogenesis.

PMID- 20134251
TI  - Investigation of possible horizontal gene transfer from transgenic rice to soil
      microorganisms in paddy rice field.
AB  - In order to monitor the possibility of horizontal gene transfer between
      transgenic rice and microorganisms in paddy rice field, the gene flow from
      bifunctional fusion (TPSP) rice containing trehalose-6-phosphate synthase and
      phosphatase to microorganisms in soils was investigated. The soil samples
      collected every month from the paddy rice field during June, 2004 to March, 2006
      were investigated by multiplex PCR, Southern hybridization, and amplified
      fragment length polymorphism (AFLP). The TPSP gene from soil genomics DNAs was
      not detected by PCR. Soil genomic DNAs were not shown its homologies on the
      Southern blotting data, indicating that gene-transfer did not occur during the
      last two years in paddy rice field. In addition, the AFLP band patterns produced
      by both soil genomic DNAs extracted from transgenic and non-transgenic rice field
      appeared similar to each other when analyzed by NTSYSpc program. Thus, these data
      suggest that transgenic rice does not give a significant impact on the
      communities of soil microorganisms although long-term observation may be needed.

PMID- 20134252
TI  - A real-time PCR assay for the quantitative detection of Ralstonia solanacearum in
      the horticultural soil and plant tissues.
AB  - A specific and rapid real-time PCR assay for detecting Ralstonia solanacearum in
      the horticultural soil and plant tissues was developed in this study. The
      specific primers RSF/RSR were designed based on the upstream region of UDP-3-O
      acyl-GlcNAc deacetylase gene from R. solanacearum, and a PCR product of 159 bp
      was amplified specifically from 28 strains of R. solanacearum, which represent
      all genetically diverse AluI types and all 6 biovars, but not from any other
      nontarget species. The detection limit of 102 CFU/g tomato stem and horticultural
      soil was achieved in this real-time PCR assay. The high sensitivity and
      specificity observed with filed samples as well as with artificially infected
      samples suggested that this method might be a useful tool for detection and
      quantification of R. solanacearum in precise forecast and diagnosis.

PMID- 20134253
TI  - Isolation of a gibberellin-producing fungus (Penicillium sp. MH7) and growth
      promotion of Crown daisy (Chrysanthemum coronarium).
AB  - Plant growth promoting fungi (PGPF) are well known for the production of useful
      secondary metabolites. However, limited information's are available on
      gibberellin (GA) production capacity of PGPF of endophytic origin. In current
      study, 15 fungal endophytes were isolated from the roots of Crown daisy, and then
      screened on Waito-c rice, in order to identify plant growth promoting fungi. The
      fungal isolate MH7 significantly increased shoot length (12.1 cm) of Waito-c in
      comparison to control treatment (7.9 cm). In a separate experiment, culture
      filtrate (CF) of MH7 significantly promoted growth attributes of Crown daisy. The
      MH7 CF was analyzed for gibberellins and it contained all physiologically active
      gibberellins (GA1, 1.37 ng/ml; GA3, 5.88 ng/ml; GA4, 8.62 ng/ml and GA7, 2.05
      ng/ml) in conjunction with physiologically inactive GA9 (0.83 ng/ml), GA12 (0.44
      ng/ml), GA15 (0.74 ng/ml), GA19 (1.16 ng/ml) and GA20 (0.98 ng/ml). The CF of MH7
      produced higher amounts of GA3, GA4, GA7, GA9 and GA12 than wild type Fusarium
      fujikuroi, which was used as control for GA production. The fungal isolate MH7
      was later identified as a new strain of Penicillium on the basis of morphological
      characteristics and phylogenetic analysis of 18S rDNA sequence.

PMID- 20134254
TI  - The gene fpk1, encoding a cAMP-dependent protein kinase catalytic subunit
      homolog, is required for hyphal growth, spore germination, and plant infection in
      Fusarium verticillioides.
AB  - Fusarium verticillioides is an important pathogen of maize responsible for ear
      rots, stalk rots and seeding blight worldwide. During the past decade F.
      verticillioides has caused several severe epidemics of maize seeding blight in
      many areas of china, which lead to significant losses. In order to understand
      molecular mechanisms regulating fungal development and pathogenicity in the
      pathogen, we isolated and characterized the gene fpk1 (GenBank accession NO.
      EF405959) encoding catalytic subunit of cAMP-dependent protein kinase, which
      include 1854 bp DNA sequence from ATG to TAA, with 1680 bp coding region, three
      intron (their length: 66bp, 54bp and 54bp), and the predicated protein had 559
      aa. The mutantdeltafpk1, which was disrupted of fpk1 gene, showed reduced
      vegetative growth, fewer and shorter aerial mycelia, strongly impaired
      conidiation and reduced spore germination rate. After germinating, the fresh
      hypha was stubby and lack of branch. When inoculated in susceptible maize
      varieties, the infection of the mutantdeltafpk1 was delayed and the infection
      efficiency was reduced than that of the wild-type. All this indicated that the
      gene fpk1 participated in hyphal growth, conidiophore producing, spore
      germination and virulence in F. verticillioides.

PMID- 20134255
TI  - Anti-allergic effects of fermented Ixeris sonchifolia and its constituent in
      mice.
AB  - To evaluate the antiallergic effect of fermented Ixeris sonchifolia (IS, family
      Compositae), we prepared IS Kimchi, isolated Lactic acid bacteria (LAB) from it,
      fermented IS with these LAB, and investigated their antiallergic effects. IS
      Kimchi more potently inhibited the passive cutaneous anaphylaxis (PCA) reaction
      induced by an IgE-antigen complex as well as the scratching behavior induced by
      compound 48/80 or histamine than IS. When IS was fermented with LAB isolated from
      IS Kimchi, its antiallergic effects was also increased. Of LAB used for
      fermentation, Lactobacillus brevis more potently increased the antiallergic
      effects. Its main constituents, chlorogenic acid and luteolin potently inhibited
      PCA reaction induced by IgE-antigen complex as well as pruritus induced by
      compound 48/80 or histamine. These constituents inhibited the expression of
      proinflammatory and allergic cytokines, TNF-alpha and IL-4, and transcription
      factor, NF-kappaB, activation induced by IgE-antigen complex in RBL-2H3 cells, as
      well as the degranulation of RBL-2H3 cells induced by an IgE-antigen complex.
      Luteolin more potently inhibited these allergic reactions than chlorogenic acid.
      These findings suggest that antiallergic effect of IS can be increased by LAB
      fermentation and fermented IS might improve allergic reactions, such as pruritus,
      anaphylaxis, and inflammation.

PMID- 20134256
TI  - Induced death of Escherichia coli encapsulated in a hollow fiber membrane as
      observed in vitro or after subcutaneous implantation.
AB  - The encapsulation of bacteria may be used to harness them for longer period of
      time in order to make them viable, while antibiotic treatment would result in
      controlled release of therapeutic molecules. Encapsulated bacteria Escherichia
      coli GFP (green fluorescent protein) (E. coli GFP) were used here as a model for
      therapeutic substance - GFP fragments release (model of bioactive substances).
      Our aim was to evaluate the performance of bacteria encapsulated in hollow fibers
      (HF) treated with antibiotic for induction of cell death. The polypropylene
      surface modified HF was applied for E. coli encapsulation. The encapsulated
      bacteria were treated with tetracycline in vitro or in vivo during subcutaneous
      implantation into mice. The HF content was evaluated in flow cytometer, to assess
      the bacteria cell membrane permeability changes induced by tetracycline
      treatment. It was observed that applied membranes prevent release of bacteria
      through the HF wall. The encapsulated in HF E. coli GFP culture in vitro proves
      the tetracycline impact on bacteria viability and allows recognition sequence of
      events within process of bacteria death. Treatment with tetracycline of the SCID
      mice for 8 hours proves the tetracycline impact on bacteria viability in vivo,
      rising the necrotic bacteria releasing GFP fragments. It was concluded, that the
      bacteria may be safely enclosed within the HF at site of implantation, and when
      the animal is treated with antibiotic bacteria may act as a local source of
      bioactive factor.

PMID- 20134257
TI  - Intensive insulin therapy reduces the urinary intercellular adhesion molecule-1
      excretion in patients with Type 2 diabetes mellitus.
AB  - OBJECTIVE: To observe the change of urinary intercellular adhesion molecule-1
      (ICAM-1) excretion in the patients with Type 2 diabetes mellitus (T2DM) compared
      to normal control group, and to investigate the effect and significance of
      insulin intensive therapy on the urinary ICAM-1 excretion. METHOD: We examined
      the urinary ICAM-1 and creatinine (Cr) of random urine in 20 patients with T2DM
      and 20 normal subjects using enzyme-linked immunosorbent assay. All diabetics
      were given intensive insulin therapy for 2 weeks, urinary ICAM- 1 and Cr was
      examined once again at the end of observation. RESULTS: Compared with the normal
      control group, not only the fasting blood glucose (FBG), post-prandial 2-h blood
      glucose (P2hBG), and glycosylated hemoglobin (HbA1c), but also the urinary ICAM-1
      to urinary Cr ratio in patients with T2DM increased significantly (p<0.01). The
      urinary ICAM-1/urinary Cr ratio of diabetics had a positive correlation with FBG
      (r=0.51, p<0.01), P2hBG (r=0.496, p<0.01), and HbA1c (r=0.478, p<0.05),
      respectively. After 2 weeks of intensive insulin therapy in Type 2 diabetics,
      both the level of blood glucose and the level of urinary ICAM-1/urinary Cr ratio
      had a remarkable decrease compared with the basal values (p<0.01). CONCLUSION:
      Intensive insulin therapy is capable of alleviating the enhanced local
      inflammation reaction of renal tissue under hyperglycemia state with the
      reduction of urinary ICAM-1 excretion.

PMID- 20134258
TI  - Endocrinology and art. The nativity--predella of "The majesty". Duccio di
      Buoninsegna (1255-1318) Siena, Italy.

PMID- 20134259
TI  - Ascites and peritonitis due to leptospirosis.

PMID- 20134260
TI  - Rifaximin and nonabsorbable disaccharides for hepatic encephalopathy.

PMID- 20134261
TI  - The diagnostic value of colonoscopic biopsies in patients with chronic diarrhea.

PMID- 20134262
TI  - Transfusion-related acute hepatic enzyme elevation: a new disease entity?

PMID- 20134265
TI  - Transcription factor POU6F1 is important for proliferation of clear cell
      adenocarcinoma of the ovary and is a potential new molecular target.
AB  - OBJECTIVE: Clear cell adenocarcinoma of the ovary often shows resistance to
      anticancer agents. It accounts for 20% of epithelial ovarian cancer in Japan
      versus around 5% in other countries. We investigated new molecules to use when
      developing molecular-targeting therapy for clear cell adenocarcinoma. METHODS:
      Reverse transcriptase polymerase chain reaction and Western blot analysis were
      performed to confirm the expression of POU6F1 in several kinds of cell lines
      derived from epithelial ovarian carcinoma. Microarray analyses were performed
      using 2 ovarian cancer microarray data sets available on the Internet.
      Immunohistochemical staining was also done to confirm both the expression and the
      localization of POU6F1 using human ovarian epithelial ovarian carcinoma tissue
      specimens. In addition, the gene cluster located downstream of transcription
      factor POU6F1 was investigated to analyze its role in the proliferation of clear
      cell adenocarcinoma of the ovary via the lysophosphatidic acid receptor, a G
      protein-coupled receptor. Furthermore, RNA interference studies with small
      interfering RNA (siRNA) were performed to assess the effect of POU6F1 on
      proliferation of xenograft tumors after injection of clear cell adenocarcinoma
      cells into nude mice. RESULTS: Expression of POU6F1 at messenger RNA and protein
      was confirmed in cell lines derived from epithelial ovarian carcinoma. The
      microarray analyses performed using the 2 ovarian cancer microarray data sets
      available on the Internet indicated that POU6F1 expression was significantly
      greater in clear cell adenocarcinoma. Immunostaining confirmed the nuclear
      localization of POU6F1 in clear cell adenocarcinoma (100%). Exposure to the siRNA
      for POU6F1 reduced the expression of lysophosphatidic acid receptors, which are G
      protein-coupled receptors involved in tumor cell proliferation. POU6F1 siRNA dose
      dependently suppressed the proliferation of clear cell adenocarcinoma cell lines,
      and a similar effect was confirmed for tumors transplanted into nude mice.
      CONCLUSIONS: Clear cell adenocarcinoma shows little response to standard therapy.
      The results of this study suggested that the transcription factor POU6F1 could be
      a new molecular target for treatment of this cancer.

PMID- 20134266
TI  - Differential expression of hypoxia-inducible protein 2 among different
      histological types of epithelial ovarian cancer and in clear cell
      adenocarcinomas.
AB  - OBJECTIVES: Epithelial ovarian cancer (EOC) can be classified into 5 major
      histological types. Among them, clear cell adenocarcinoma (CCC) has a poor
      response to chemotherapy and poor prognosis compared with other histological
      types. Previously, we reported that the hypoxia-inducible protein 2 (HIG2) gene
      might be a new biomarker for CCCs, based on its expression profile. In this
      study, we generated a polyclonal antiserum to HIG2 to explore the use of HIG2 as
      a predictive biomarker in EOC. In addition, HIG2 expression was evaluated in
      uterine endometrial and renal CCCs. METHODS: Hypoxia-inducible protein 2
      expression was analyzed by immunohistochemistry in formalin-fixed surgical
      samples from 254 EOC, 17 endometrial, and 29 renal CCC patients. RESULTS: Hypoxia
      inducible protein 2 is expressed in 175 of 254 ovarian cancer cases. Cytoplasmic
      HIG2 expression is significantly more frequent in ovarian CCC (83.1%) than in
      serous (54.9%, P = 0.0001), mucinous (40%, P = 0.00002), or endometrioid (58.1%,
      P = 0.003) adenocarcinoma. The chemoresponse rate was higher in 24 ovarian CCC
      patients with cytoplasmic HIG2 expression than in 6 CCC patients without HIG2
      expression (62.5% [15/24] vs 0% [0/6], P = 0.02). In contrast, there was no
      relationship between nuclear HIG2 expression and chemoresponse. Cytoplasmic and
      nuclear HIG2 expressions are significantly more frequent in ovarian and uterine
      than renal CCC (P = 0.04). CONCLUSIONS: Hypoxia-inducible protein 2 may be used
      as a marker for early detection of ovarian CCCs or for prediction of response to
      chemotherapy, but HIG2 expression does not predict survival of patients with CCC.

PMID- 20134267
TI  - Down-regulation of HLA class I antigen in human papillomavirus type 16 E7
      expressing HaCaT cells: correlate with TAP-1 expression.
AB  - OBJECTIVES: High-risk human papillomaviruses (HPVs) are the major causative
      agents of cervical cancer, and the E6 and E7 genes encode the major HPV
      oncoproteins. The E7 protein of high-risk HPV types disturbs cell cycle control
      and down-regulates components of the antigen presentation pathway, suggesting a
      role for E7 in tumor immune evasion. We previously reported that HPV-16 E7
      expression and down-regulation of HLA class I was highly correlated in cervical
      lesions. This study was aimed to determine whether HPV-16 E7 oncoprotein could
      down-regulate surface HLA class I antigen in HPV-16 E7-transfected cells, and
      whether it had correlation with the expression of the transporter associated with
      antigen processing (TAP). METHODS: The HPV-16 E7 open reading frame was
      transfected into HaCaT cells. After G418 selection, resistant colonies were
      individually picked and expanded into clonal cell lines. Using the fluoresence
      activated cell sorting analysis, the levels of cell surface HLA class I antigen
      and intracellular TAP-1 and TAP-2 expressions were detected. RESULTS: Compared
      with the empty vector control, a statistical significant decrease of
      approximately 50% in cell surface HLA class I expression was observed in HPV-16
      E7 expressing HaCaT cells (P < 0.001). Moreover, the expression of HPV-16 E7 in
      HaCaT cells resulted in decreased expression of TAP-1 that was essential for HLA
      class I expression at the cell surface, a statistical significant decrease of
      approximately 40% compared with that with the empty vector control (P < 0.001).
      CONCLUSIONS: Our finding demonstrates that HPV-16 E7 down-regulates surface HLA
      class I antigen, which in part correlates with the decrease of TAP-1.

PMID- 20134268
TI  - Prechemotherapy serum levels of CD105, transforming growth factor beta2, and
      vascular endothelial growth factor are associated with prognosis in patients with
      advanced epithelial ovarian cancer treated with cytoreductive surgery and
      platinum-based chemotherapy.
AB  - BACKGROUND: Serum CD105 has been associated with angiogenic activity in cancer,
      and low CD105 expression has been associated with improved prognosis. The present
      study evaluated the prognostic significance of serum levels of CD105 and related
      factors in patients with epithelial ovarian cancer (EOC) after cytoreductive
      surgery and chemotherapy. PATIENTS AND METHODS: Eighty-six patients with stages
      IIC to IV EOC treated postoperatively with platinum-based chemotherapy were
      included. The enzyme-linked immunosorbent assay was used to measure
      prechemotherapy serum levels of CD105, transforming growth factor beta1/2 (TGF
      beta1/2), angiopoietin 2, vascular endothelial growth factor, and tumor necrosis
      factor-alpha. RESULTS: High levels of TGF-beta2 (>8908.86 pg/mL) and CD105 (>4.25
      ng/mL) were independently associated with improved overall survival (not reached
      vs 39 months, P = 0.009 and 75 vs 39 months, P = 0.029, respectively), whereas a
      high level of TGF-beta2 and a low level of vascular endothelial growth factor
      (<219.04 pg/mL) were independently associated with improved progression-free
      survival (49 vs 17 months, P = 0.022 and 57 vs 16 months, P = 0.023,
      respectively). Among patients with favorable (>4.25 ng/mL) CD105 levels, only
      patients with low TGF-beta1 levels (<177.1 ng/mL) had superior survival than
      patients with low CD105 levels. CONCLUSIONS: Our study confirms the prognostic
      significance of angiogenesis in EOC and supports a biological interaction between
      CD105 and TGF-beta1. High angiogenic activity may be associated by increased
      efficacy of postoperative chemotherapy.

PMID- 20134269
TI  - Metastatic uterine leiomyosarcomas: a single-institution experience.
AB  - BACKGROUND: Uterine leiomyosarcoma (LMS) is a rare disease and, when it recurs or
      metastasizes, can rarely be cured. In a retrospective study, we summarized our
      experience in treating a large cohort of patients with metastatic uterine LMS.
      MATERIALS AND METHODS: Cases of recurrent or metastatic uterine LMS diagnosed
      between 2000 and 2008 were analyzed. Survival was determined from the time of
      initial diagnosis to last follow-up. RESULTS: Thirty-three patients (median age,
      55 years) were identified. Eighteen patients were initially diagnosed with
      localized disease. Median disease-free interval was 5.25 months, and overall
      survival (OS) is 43.7 months. Median OS of 15 patients with initially discovered
      metastatic disease is 31.4 months. Different chemotherapy regimens produced
      approximately 30% response rates. Twelve patients underwent at least 1 surgical
      resection of pulmonary or extrapulmonary metastases. In this group, median
      progression-free survival was 7.9 months (range, 0-33.9 months), median OS was
      45.2 months (range, >8.1-78.8 months), 2-year survival rate was 83%, and 4-year
      survival rate was 25%. CONCLUSIONS: Very few patients with recurrent or
      metastatic uterine LMS can be curatively treated. Our experience suggests that
      modern multimodal therapy or combining chemotherapy with aggressive surgery in
      selected patients may be significant in prolonging survival of women with this
      fatal disease.

PMID- 20134270
TI  - Effect of type-specific human papillomavirus incidence on screening performance
      and cost.
AB  - BACKGROUND: Implementation of human papillomavirus (HPV) vaccination is expected
      to change the epidemiology of HPV infection. METHODS: Using age-dependent
      (inhomogeneous) Markov chains, we tested the effect of type-specific (ie, HPV
      16/HPV-18 and other high-risk HPV types) HPV incidence on 3 screening strategies
      in a cohort of 100,000 women, starting screening at the age of 25 years and
      continuing until the age of 34 years. All the strategies started with an HPV
      test; if the result was positive, the next step was triage with cytology
      (strategy 1), cytology and colposcopy together (strategy 2), or colposcopy only
      (strategy 3). Published background data were used for the models. RESULTS:
      Strategy 2 had the highest sensitivity; the absolute number of missed cervical
      intraepithelial neoplasia (CIN)3+ cases was associated with HPV incidence in all
      the strategies, but their relative sensitivity remained unaffected. Strategy 2
      was cheaper per diagnosed CIN3+ for very low HPV incidence rates, but this
      changed for higher incidence rates. For any given pair of HPV-16/HPV-18 and other
      high-risk-type incidence, the cost of the triage and the total cost of screening
      was highest in screening 2 and lowest in screening 1. For each screening
      strategy, the cost per diagnosed CIN3+ was mainly determined by the incidence of
      HPV-16/HPV-18, and the cost of the triage and the total screening cost by the
      incidence of other high-risk types. CONCLUSIONS: Type-specific HPV incidence
      affects the absolute number of missed CIN3+ cases and the cost of screening in a
      mathematically describable way and can be used for prediction of changes in these
      outcomes with changing HPV epidemiology.

PMID- 20134271
TI  - Diagnostic efficacy of real-time optical coherence tomography in the management
      of preinvasive and invasive neoplasia of the uterine cervix.
AB  - OBJECTIVE: Determine the sensitivity and specificity of optical coherence
      tomography (OCT) as an adjunct to colposcopy in the detection of cervical
      intraepithelial neoplasia (CIN) grade 2 or higher in a real-time clinical
      evaluation. BACKGROUND: Optical coherence tomography (OCT) uses infrared light
      similar to ultrasound pulse-echo imaging. Image resolution is optimal in the 1-to
      3-mm range. This study is the third in our series of OCT investigations and our
      first real-time clinical trial. The study was conducted at the Peking University
      Shenzhen Hospital, Shenzhen, China. METHODS: Nonpregnant women 18 years or older
      with abnormal cervical cytologic findings or a positive high-risk human
      papillomavirus test result were recruited. Women were assessed; and diagnoses,
      recorded by cervical quadrant first with colposcopy, followed by colposcopic
      directed OCT. A biopsy of the abnormal areas was performed. In normal quadrants,
      biopsy specimens were obtained at the 2-, 4-, 8-, and 10-o'clock positions at the
      squamocolumnar junction depending on the quadrant. An endocervical curettage was
      also done. Individual OCT diagnoses were paired with colposcopic impressions and
      biopsy specimens to assess its role as a paired secondary screen. Data were
      analyzed using generalized estimating equations to control for correlation within
      a woman. RESULTS: One thousand two hundred thirty-seven paired diagnoses from 299
      women were analyzed. Median age was 36 years. Ninety-six women (8%) had a
      diagnosis of CIN 2 or higher. Evaluation by quadrant showed that the sensitivity
      for CIN 2 or higher decreased by adding OCT to colposcopy, but the specificity
      increased from 83% to 93%. CONCLUSIONS: We continue to try to improve sensitivity
      by improving the near-infrared light source, decreasing the scan time to 8 frames
      per second, and using a larger diameter (5 mm) fiberoptic probe with a newly
      designed application specific probe sheath.

PMID- 20134272
TI  - Human papillomavirus L1 capsid protein and human papillomavirus type 16 as
      prognostic markers in cervical intraepithelial neoplasia 1.
AB  - INTRODUCTION: The aim of the study was to determine whether human papillomavirus
      (HPV) L1 capsid protein and the HPV genotype can predict the disease course as
      prognostic markers for cervical intraepithelial neoplasia 1 (CIN1). METHODS:
      Immunohistochemical staining was performed for HPV L1 capsid protein in 101 women
      who had been confirmed to have CIN1 by histologic examination and HPV high-risk
      infection by HPV genotyping. The disease course was analyzed by follow-up
      histologic examination according to the HPV L1 capsid protein and HPV genotype
      over a minimum of 12 months. RESULTS: The CIN1 regressed spontaneously in 60.4%
      of the women; most cases of regression occurred within 1 year (90.9% of
      regression cases). The HPV L1 capsid protein-positive patients had a spontaneous
      regression rate of 72.7% (48/66) and a rate of persistent disease or progression
      to higher grade disease of 27.3% (18/66). The HPV L1 capsid protein-negative
      women had a regression rate of 37.1% (13/35) and a rate of persistent disease or
      progression of 62.9% (22/35; P < 0.001). The HPV-16-infected patients had a
      regression rate of 38.6% (17/44) and a rate of persistent disease or progression
      of 61.4% (27/44), whereas the non-HPV-16-infected patients had a regression rate
      of 77.2% (44/57) and a rate of persistent disease or progression of 22.8% (13/57;
      P < 0.001). CONCLUSIONS: The HPV L1 protein expression is closely related to
      spontaneous disease regression, but HPV-16 infection is related to persistent
      disease or progression to high-grade lesions in patients with CIN1.

PMID- 20134273
TI  - Clinical analysis of 21 cases of nongestational ovarian choriocarcinoma.
AB  - INTRODUCTION: The objective of the study was to investigate the clinical
      characters, diagnosis, treatment, and prognosis of nongestational ovarian
      choriocarcinoma. METHODS: A retrospective analysis was done on 21 patients with
      nongestational ovarian choriocarcinoma treated in Peking Union Medical College
      Hospital from January 1985 to October 2008. All patients' conditions were
      diagnosed by histopathologic examination; in 3 of them, the diagnosis was
      confirmed by DNA polymorphism analysis at 12 short tandem repeat loci. RESULTS:
      Correct diagnosis was achieved in only 3 patients before initial treatment. All
      patients received standard multiple-drug combined chemotherapy and underwent an
      operation. The mean number of chemotherapy courses for each patient was 10. Of
      the 21 patients, 16 achieved complete remission, and 4 obtained partial
      remission; 1 died. In a median follow-up of 71.4 months, the 5-year overall
      survival rate was 79.4%. CONCLUSIONS: The early diagnosis of nongestational
      ovarian choriocarcinoma is expected to be improved. DNA polymorphism analysis is
      a useful tool in determining the origin of ovarian choriocarcinoma. The prognosis
      is optimistic if managed with standard multiple-drug chemotherapy combined with
      surgical treatment.

PMID- 20134274
TI  - Clinical experiences on aggressive angiomyxoma in China (report of 93 cases).
AB  - OBJECTIVE: To discuss the clinical experiences of aggressive angiomyxoma (AAM) by
      summarizing clinical information of patients with this disease in China. METHODS:
      Chinese articles concerning AAM were retrospectively reviewed and analyzed.
      RESULTS: A total of 93 cases in 44 well-documented articles had been reported,
      among which 11 were male and 82 were female, with a male to female ratio of
      1:7.45. The age of the females varied from 14 to 55 years (mean [SD], 37.17
      [10.39] years; median, 38.5 years), whereas that of the males ranged from 15 to
      65 years (mean [SD], 44.75 [17.61] years; median, 55 years), which was
      significantly higher than that of the females (t = 2.082, P = 0.041). The most
      common sites were the perineum in females and the scrotum in males. None of the
      cases could be accurately diagnosed as AAM preoperatively. The mean minimum
      diameter of the tumors was 4.62 (3.51) cm, and the maximum was 9.12 (8.23) cm.
      All the specimens showed typical pathological features of AAM as reported
      previously. Immunohistochemistry indicated that AAM tended to be strongly
      positive for vimentin, smooth-muscle actin, and CD34 but mostly negative for S
      100 and CD68. The duration of the postoperative follow-up was 3 to 96 months
      (mean [SD], 28.5 [18.86] months; median, 9.5 months) in 44 cases, with a
      recurrence rate of 31.82%. CONCLUSIONS: Aggressive angiomyxoma must be considered
      in the differential diagnosis of any female with an asymptomatic perineal mass. A
      complete margin-free excision should be achieved to avoid recurrence. Long-term
      follow-up is quite necessary because of the high rate of local recurrence.

PMID- 20134275
TI  - Subcutaneous methylnaltrexone to restore postoperative bowel function in a long
      term opiate user.
AB  - INTRODUCTION: One of the most common undesired effects of analgesic opioid use
      and addiction is constipation. Numerous pharmacologic agents have been used to
      treat opioid-induced bowel hypomotility with limited success. Methylnaltrexone
      bromide (MNTX) selectively targets the peripheral adverse effects of opioids
      while preserving the central analgesic effects of opioid agonist treatment. CASE:
      While it is indicated for use in nonsurgical patients in the palliative care
      setting, here we report the use of MNTX for the alleviation of postoperative
      ileus in a heroin user with recurrent cervical cancer undergoing diverting
      colostomy and urinary conduit placement. CONCLUSIONS: Results suggest that MNTX
      may accelerate postoperative gastrointestinal recovery in opioid-dependent
      patients. Further studies are warranted to evaluate its role in the pharmacologic
      management of postoperative ileus.

PMID- 20134276
TI  - Therapeutic intent and misconception in early-phase clinical trials in the
      gynecologic malignancies.

PMID- 20134278
TI  - Alarming trends in prevalence of low cardiovascular risk factor burden.

PMID- 20134279
TI  - Improving heart failure symptom recognition: a diary analysis.
AB  - BACKGROUND: Heart failure (HF) is a costly and highly disabling syndrome
      affecting nearly 5 million individuals yearly. Lifestyle changes are crucial to
      the successful management of HF, and daily weight monitoring is an essential
      component of self-care. Daily weights provide an objective indicator of fluid
      volume status in patients with HF. However, the practice of performing daily
      weights is underappreciated and infrequently implemented by patients. This may
      contribute to an inability to recognize worsening HF and, ultimately, delay in
      seeking medical care. OBJECTIVE: The aim of this study was to evaluate weight
      monitoring diaries for adherence to daily weight monitoring, reasons for
      nonadherence, prevalence of weight gain of 3 lb or more in 1 day, and medical
      advice-seeking behavior after weight gain in a sample of patients with documented
      HF. METHODS: A cohort study design was used to analyze data from 20 HF patients
      who participated in a tailored, one-on-one educational intervention. The analysis
      is part of a parent pilot study designed to improve symptom recognition and
      response to symptoms of fluid overload. Diary data were collected for 3 months
      after the intervention. The diaries provided information regarding symptoms that
      participants experienced, daily weights, and a record of unplanned hospital
      visits or contacts with their physician. RESULTS: Of 20 participants in the
      study, 16 returned diaries for analysis. Two participants withdrew participation
      before the conclusion of the study and 2 participants who claimed to have
      completed their diary never returned the diary despite repeated reminders and
      telephone calls. Sixteen participant diaries were therefore available for
      analysis. The mean adherence score for these 16 participants was 79.4%. Seventy
      five percent had weight gains of 3 lb or more in 1 day and only 1 person
      contacted his/her physician for weight gain. Vacation time was the most common
      reason for weighing nonadherence. CONCLUSION: This study revealed high adherence
      to daily weights in patients receiving an education session focused on fluid
      weight management. However, behavior related to daily weights did not lead to
      more appropriate use of physician or provider consultation. Diaries offer promise
      for symptom management and an opportunity for patients to engage in self-care;
      however, clinicians need to encourage patients to use the diary data to seek
      prompt medical care.

PMID- 20134280
TI  - Shared medical appointments: improving access, outcomes, and satisfaction for
      patients with chronic cardiac diseases.
AB  - Improving access to care, health outcomes, and patient satisfaction are primary
      objectives for healthcare practices. This article outlines benefits, concerns,
      and possible challenges of shared medical appointments (SMAs) for patients and
      providers. The SMA model was designed to support providers' demanding schedules
      by allowing patients with the same chronic condition to be seen in a group
      setting. By concentrating on patient education and disease management,
      interactive meetings provide an opportunity for patients to share both successes
      and struggles with others experiencing similar challenges. Studies demonstrated
      that SMAs improved patient access, enhanced outcomes, and promoted patient
      satisfaction. This article describes the potential benefits of SMAs for patients
      with chronic heart disease, which consumes a large number of healthcare dollars
      related to hospital admissions, acute exacerbations, and symptom management.
      Education for self-management of chronic disease can become repetitive and time
      consuming. The SMA model introduces a fresh and unique style of healthcare
      visits, allowing providers to devote more time and attention to patients and
      improve productivity. The SMA model provides an outstanding method for nurse
      practitioners to demonstrate their role as a primary care provider, by leading
      patients in group discussions and evaluating their current health status. Patient
      selection, preparation, and facilitation of an SMA are discussed to demonstrate
      the complementary nature of an SMA approach in a healthcare practice.

PMID- 20134281
TI  - Ankle brachial index as a prognostic tool for women with coronary artery disease.
AB  - BACKGROUND AND OBJECTIVES: Coronary artery disease (CAD) is the leading cause of
      death among women both nationally and internationally. Despite increased
      knowledge regarding CAD in women, early diagnosis remains a difficult clinical
      task. A correlation between peripheral arterial disease (PAD) and CAD has been
      noted in previous research; however, these studies were either retrospective or
      did not focus on women. This research investigates the correlation of ankle
      brachial index (ABI), measurements used to diagnose PAD, and presence of CAD in
      women, in an effort to determine the predictive value of ABI specifically in
      women. SUBJECTS AND METHODS: A prospective correlation design was used to study
      women (n = 30) who were undergoing a diagnostic cardiac catheterization. Ankle
      brachial index readings were obtained prior to the catheterization procedure.
      Catheterization findings were grouped according to absence of CAD or presence of
      1-vessel or multivessel CAD and coupled with each woman's ABI and recorded
      cardiovascular risk factors. RESULTS: Peripheral arterial disease (based on ABI
      of <0.90 mm Hg) was found in 13.3% of the women. A significant correlation was
      found between ABI of less than 0.90 mm Hg and increasing age (t = -2.30, P
      =.029). Coronary artery disease was found in 82.1% of the women; more than half
      (57.1%) had multivessel disease. Absence of CAD was noted in 17.9%. Women with
      CAD were older than women without CAD (F = 3.86, P =.035). No significant
      differences were found between presence or absence of PAD based on ABI and
      diagnosis of no coronary disease or 1-vessel or multivessel coronary disease.
      CONCLUSIONS: This study failed to show the expected correlation between ABI of
      less than 0.90 mm Hg and CAD, but did show a significant correlation of age with
      presence of both PAD and CAD. Further research that focuses specifically on women
      is needed and should include a larger sample, additional unique cardiovascular
      risk factors, and innovative diagnostic tests to determine presence of CAD in
      women early in the disease process.

PMID- 20134282
TI  - Critical review of health-related quality of life studies of patients with aortic
      stenosis.
AB  - BACKGROUND: While studies of health-related quality of life (HRQOL) are
      increasing among cardiovascular patients, very few have examined HRQOL in persons
      with aortic stenosis (AS). PURPOSE: A critical review of studies (1997-2008) of
      HRQOL in persons with AS was conducted to summarize findings and identify
      clinical and research implications. RESULTS: Twenty-eight studies were
      identified, all of which were quantitative and evaluated HRQOL after aortic valve
      replacement (AVR). No studies conducted by nurses or studies measuring HRQOL in
      persons who did not undergo AVR were found. The literature focused on age and
      type of valve as variables influencing HRQOL postoperatively. Although results
      varied, elderly patients often scored similar or better than comparison groups.
      Health-related quality of life was found to be affected by valve noise and
      anticoagulation rather than the specific valve type when comparing patients
      receiving biological versus mechanical valves. CONCLUSIONS: Selection for surgery
      should not be based on age alone. Early consideration should be given to symptoms
      prior to surgery because of evidence that patients with fewer symptoms
      preoperatively have better HRQOL after AVR. Anticoagulation status should be
      evaluated as an independent variable of HRQOL in future studies. IMPLICATIONS FOR
      RESEARCH AND PRACTICE: Researchers need to augment generic HRQOL measures with
      disease-specific items that may pertain to life areas affected by AS, such as
      audible valve click, wound healing, and dyspnea. Future research should be
      inclusive of AS patients who do not undergo surgery. Nurses in a variety of roles
      can work independently or within a multidisciplinary team to provide
      interventions for the promotion of HRQOL for patients across all stages of the AS
      disease process.

PMID- 20134283
TI  - Prevalence of the metabolic syndrome among overweight and obese college students
      in Korea.
AB  - OBJECTIVES: This study examined the prevalence of metabolic risk factors among
      overweight and obese college students aged 18 to 29 years in Korea. METHODS:
      Baseline data from a healthy lifestyle intervention study for overweight and
      obese college students in Korea were used. We recruited the sample (N = 73) (84%
      male; mean [SD] age, 23.77 [2.45] years) from 2 universities in Seoul, Korea, and
      measured body mass index, waist-hip circumstance, blood pressure, and fasting
      blood chemistry. Descriptive statistics, Spearman rank order correlations, and
      analysis of variance were conducted using SPSS 16.0 (SPSS Inc, Chicago, Illinois)
      for windows. RESULTS: Three-fourths of the participants were identified as being
      viscerally obese based on the Asia Pacific criteria. Of the total sample, about
      12% and 20% were defined as having metabolic syndrome according to the National
      Cholesterol Education Program--the Adult Treatment Panel III and International
      Diabetes Federation, respectively. Concordance between the National Cholesterol
      Education Program--the Adult Treatment Panel III and International Diabetes
      Federation definitions was very good in the current study (Cohen kappa
      coefficient = 0.74, P <.001). Body mass index was significantly correlated with
      greater triglyceride and systolic and diastolic blood pressure and waist
      circumference but with lower high-density lipoprotein cholesterol. CONCLUSIONS:
      Early screening and targeted interventions to prevent obesity and the metabolic
      syndrome are urgently needed to promote health for adolescents and young adults
      in South Korea.

PMID- 20134284
TI  - Motivating people to learn cardiopulmonary resuscitation and use of automated
      external defibrillators.
AB  - The purpose of this study was to test the effect of a motivational message on the
      intention of laypersons to learn cardiopulmonary resuscitation (CPR) and
      automated external defibrillator (AED) use. A pretest-posttest, double-blind,
      randomized design was used with 220 community-dwelling adults. Participants were
      randomly assigned to the treatment group reading the CPR and AED pamphlet
      emphasizing learning CPR and AED use to save someone they love and the 3-minute
      window for response time; or to the comparison group reading the identical
      pamphlet without the 2 motivational statements. Intention to learn CPR and AED
      use and to look for AEDs in public areas was measured before and after reading
      the respective pamphlet. No significant difference emerged between the groups for
      the number of participants planning to learn CPR and AED use. A significant
      number of participants in both groups increased intention to learn CPR and AED
      use. Significantly more treatment participants than comparison participants
      planned to routinely look for AEDs in public areas after reading the pamphlet,
      however. Teaching critical facts such as the low survival rate for out-of
      hospital cardiac arrest might encourage laypersons to learn CPR and AED use.
      Routinely teaching family members of people at risk for a cardiac arrest about
      the short window of time in which CPR and AED use must begin and encouraging them
      to learn about CPR and AEDs to save someone they love may encourage family
      members to identify the location of AEDs in public places.

PMID- 20134285
TI  - Nursing care practices following a percutaneous coronary intervention: results of
      a survey of Australian and New Zealand cardiovascular nurses.
AB  - BACKGROUND: Although there is high-level evidence to guide optimal medical care
      for percutaneous coronary interventions, there are less explicit guidelines to
      support nurses in providing care. AIM: This study describes the practice
      standards and priorities of care of cardiovascular nurses in Australia and New
      Zealand. METHOD: Item generation for the survey was informed by an integrative
      literature review and existing clinical guidelines. A 116-item Web-based survey
      was administered to cardiovascular nurses, via electronic mail lists of
      professional cardiovascular nursing organizations, using a secure online data
      collection system. RESULTS: Data were collected from March 2008 to March 2009. A
      total of 148 respondents attempted the survey, with 110 (74.3%) completing all
      items. All respondents were registered nurses with an average of 12.3 (SD, 7.61)
      years of clinical experience in the cardiovascular setting. A range of practice
      patterns was evident in ambulation time after percutaneous coronary intervention,
      methods of sheath removal, pain relief, and patient positioning. Respondents
      consistently rated psychosocial care a lower priority than other tasks and also
      identified a knowledge deficit in this area. CONCLUSION: This survey identified
      diversity of practice patterns and a range of educational needs. Increasing
      evidence to support evidence-based practice and guideline development is
      necessary to promote high-quality care and improved patient outcomes.

PMID- 20134287
TI  - A short report comparing outcomes between L4/L5 and L5/S1 single-level discectomy
      surgery.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To assess whether there is a
      difference in outcome between single-level discectomy at L4/L5 and L5/S1. SUMMARY
      OF BACKGROUND DATA: There is sound biomechanical reasoning to suspect a
      difference between spinal levels. The L4/L5 disc is more susceptible to axial
      torsion and is the most common site of lumbar instability. The L5/S1 motion
      segment is protected from torsional strain by extensive iliolumbar ligaments but
      is more exposed to axial compressive forces. The available literature does not
      include studies with preoperative standard outcome measures. METHODS:
      Prospectively gathered data from a single center. The outcome measures were the
      Oswestry disability index, subjective walking distance, modified somatic
      perception, modified Zung depression index, low back outcome score, and visual
      analog score. Comparisons between L4/L5 and L5/S1 levels were made with these
      outcome measures using the Student t test. RESULTS: Seventy-seven L5/S1 and 53
      L4/L5 discectomies were performed. There were no clinically significant
      differences. Preoperative walking distance for L5/S1 patients was longer than at
      L4/L5 (455 m vs. 278 m; P=0.027). At 6 months a difference also exists with the
      low back outcome score [47.11 (L4/L5) vs. 39.47 (L5/S1); P=0.0229]. After 12
      months at L5/S1, men had a better Oswestry disability index score than women (17%
      vs. 32%; P=0.038). Across all other parameters, no significant difference was
      found to exist between the 2 groups. There was no difference in the recurrence
      rate or reoperation rate. CONCLUSIONS: This is the first study comparing a
      discectomy outcome at L4/L5 and L5/S1 with complete preoperative data. No
      significant difference exists between the 2 levels in terms of postoperative
      outcome. Surgical procedures such as fusion or arthroplasty should not be carried
      out synchronous with primary discectomy for radiculopathy. The lack of a
      difference between L4/L5 and L5/S1 reinforces the fact that the mechanical
      environment does not affect outcome and should not influence treatment.

PMID- 20134288
TI  - Safety of posterior interbody fusions of the lumbar spine using rhBMP-2.

PMID- 20134296
TI  - ACOG Practice Bulletin no. 109: Cervical cytology screening.

PMID- 20134298
TI  - ACOG Committee Opinion No. 447: Patient safety in obstetrics and gynecology.

PMID- 20134299
TI  - ACOG Committee Opinion No. 448: Menstrual manipulation for adolescents with
      disabilities.
AB  - Defining the reasons for intervention and the precise goal of treatment are the
      most critical issues regarding use of interventions to alter menstrual flow in
      adolescents with disabilities. Reasons for intervention may relate to abnormal
      uterine bleeding, hygiene, mood issues, fear of pregnancy, and acute onset of
      other medical conditions. Goals of treatment may include a decrease in the amount
      of bleeding, periodic amenorrhea, or treatment of symptoms, such as mood issues
      or dysmenorrhea. First-line treatment options should be safe, minimally invasive,
      and nonpermanent. Endometrial ablation has not been studied in adolescents, has
      not been studied longterm, is considered irreversible and, therefore, is not
      recommended in teenagers.

PMID- 20134300
TI  - ACOG Committee Opinion No. 449: Maternal phenylketonuria.
AB  - Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe)
      metabolism characterized by a deficiency of the hepatic enzyme, phenylalanine
      hydroxylase, an enzyme responsible for the conversion of phenylalanine to
      tyrosine, and elevated levels of Phe and Phe metabolite. All women with PKU or
      hyperphenylalaninemia should be strongly encouraged to receive family planning
      and preconception counseling. Women with PKU or hyperphenylalaninemia should
      begin appropriate, medically directed dietary phenylalanine restriction before
      conception.

PMID- 20134301
TI  - ACOG Committee Opinion no. 450: Increasing use of contraceptive implants and
      intrauterine devices to reduce unintended pregnancy.
AB  - High unintended pregnancy rates in the United States may in part be the result of
      relatively low use of long-acting reversible contraceptive (LARC) methods,
      specifically the contraceptive implant and intrauterine devices. Top-tier
      reversible methods share the characteristic of requiring a single act of
      motivation for long-term use, eliminating adherence and user-dependence from the
      effectiveness equation. According to the World Health Organization's evidence
      based Medical Eligibility Criteria for contraceptive use, LARC methods have few
      contraindications, and almost all women are eligible for implants and
      intrauterine devices. Because of these advantages and the potential to reduce
      unintended pregnancy rates, LARC methods should be offered as first-line
      contraceptive methods and encouraged as options for most women. To increase use
      of LARC methods, barriers such as lack of health care provider knowledge or
      skills, low patient awareness, and high upfront costs must be addressed.

PMID- 20134302
TI  - ACOG Committee Opinion No. 451: Von Willebrand disease in women.
AB  - Approximately 3 million women in the United States have inherited bleeding
      disorders. The prevalence of bleeding disorders is particularly high among women
      with menorrhagia. Von Willebrand disease is the most common inherited bleeding
      disorder. Once a diagnosis is made, collaboration with a hematologist is helpful
      for long-term management. Women with von Willebrand disease may be at increased
      risk for gynecologic and obstetric complications. Many treatments are available
      for the control of menorrhagia in women with von Willebrand disease, but the
      first-line therapy remains combined hormonal contraception.

PMID- 20134303
TI  - ACOG Committee Opinion No. 452: Primary and preventive care: periodic
      assessments.
AB  - Periodic assessments offer an excellent opportunity for obstetricians and
      gynecologists to provide preventive screening, evaluation, and counseling. The
      American College of Obstetricians and Gynecologists' Committee on Gynecologic
      Practice recommends routine assessments in primary and preventive care for women
      based on age and risk factors.

PMID- 20134305
TI  - The role of assistive robotics in the lives of persons with disability.
AB  - Robotic assistive devices are used increasingly to improve the independence and
      quality of life of persons with disabilities. Devices as varied as robotic
      feeders, smart-powered wheelchairs, independent mobile robots, and socially
      assistive robots are becoming more clinically relevant. There is a growing
      importance for the rehabilitation professional to be aware of available systems
      and ongoing research efforts. The aim of this article is to describe the advances
      in assistive robotics that are relevant to professionals serving persons with
      disabilities. This review breaks down relevant advances into categories of
      Assistive Robotic Systems, User Interfaces and Control Systems, Sensory and
      Feedback Systems, and User Perspectives. An understanding of the direction that
      assistive robotics is taking is important for the clinician and researcher alike;
      this review is intended to address this need.

PMID- 20134306
TI  - Comparison between botulinum toxin and corticosteroid injection in the treatment
      of acute and subacute tennis elbow: a prospective, randomized, double-blind,
      active drug-controlled pilot study.
AB  - OBJECTIVE: To compare botulinum toxin type A injection with corticosteroid
      injection in the treatment of tennis elbow. DESIGN: In this prospective,
      randomized, double-blind, drug-controlled trial,19 affected elbows of 16 patients
      were randomly assigned to receive injection with botulinum toxin type A (Botox
      group) or triamcinolone acetonide (steroid group). We used the Visual Analog
      Scale, pain-free grip strength, and World Health Organization Quality of Life
      Brief Questionnaire to assess the perception of pain, grip strength, and quality
      of life, respectively. Measures were performed before and at 4, 8, and 12 wks
      after the treatment. RESULTS: Four weeks after the treatment, the Botox group had
      smaller decrease in pain (P = 0.02) but greater decrease in grip strength (P =
      0.01). The difference in grip strength remained significant at 8 wks (P = 0.03).
      No significant differences in quality of life were observed throughout the study
      period. CONCLUSIONS: Corticosteroid is superior to botulinum toxin type A in
      relieving pain in tennis elbow at 4 wks after injection. Because botulinum toxin
      injection did not relieve pain significantly but is associated with weakness, the
      muscle weakness caused by botulinum toxin is unlikely to be the sole mechanism of
      the pain relief observed in previous studies.

PMID- 20134307
TI  - Early postoperative maximal strength training improves work efficiency 6-12
      months after osteoarthritis-induced total hip arthroplasty in patients younger
      than 60 years.
AB  - OBJECTIVE: To assess physical outcome of early maximal strength training after
      total hip arthroplasty. DESIGN: Six- and 12-mo follow-up of 24 (22) total hip
      arthroplasty patients randomly assigned to 4 wks of maximal strength training and
      conventional rehabilitation and to conventional rehabilitation only was
      conducted. After the intervention period, all patients attended conventional
      rehabilitation. Outcome measures were hip abduction and leg press strength, gait
      patterns, work efficiency, maximal oxygen consumption, and health-related quality
      of life. RESULTS: Work efficiency was significantly higher in the strength
      training and conventional rehabilitation group compared with the conventional
      rehabilitation-only group after 6 and 12 mos by 29% and 30%, respectively. Leg
      press for the healthy leg and rate of force development for the operated leg were
      significantly higher in the strength training and conventional rehabilitation
      group compared with the conventional rehabilitation-only group 12 mos
      postoperatively by 36% and 74%, respectively. CONCLUSIONS: This study
      demonstrates higher work efficiency after 6 and 12 mos and improved rate of force
      development after 12 mos in total hip arthroplasty patients who performed early
      maximal strength training combined with conventional rehabilitation after total
      hip arthroplasty surgery compared with total hip arthroplasty patients receiving
      conventional rehabilitation only. However, the study indicates that a prolonged
      maximal strength training program and aerobic endurance training are required to
      fully recover total hip arthroplasty patients.

PMID- 20134308
TI  - Outcomes of a standardized surgical and rehabilitation program in transtibial
      amputation for peripheral vascular disease: a prospective cohort study.
AB  - OBJECTIVE: To study the outcomes of a new surgical and rehabilitation program for
      initial unilateral transtibial amputation in patients with peripheral vascular
      disease. The program consists of sagittal incision, rigid dressing, compression
      therapy using silicone liner, and direct manufacturing prosthetic technique.
      DESIGN: A prospective cohort study with 1-yr follow-up. RESULTS: Of the 217
      consecutive patients with peripheral vascular disease who underwent transtibial
      amputation (mean age, 77 yrs; 51% diabetic; 116 could walk before amputation),
      119 (55%) were fitted with a prosthesis at a median time of 41 (range, 12-147)
      days after amputation. Of the prosthetic recipients, 76 (64%) obtained good
      function with the prosthesis within 6 mos. Within 1 yr, reamputation was
      performed on 8.2%, and contralateral amputation was performed on 5.5%. The 90-day
      mortality was 24% (53 patients). The total 1-yr mortality was 40% (86 patients):
      17% among patients who received a prosthesis and 67% among those who did not
      receive a prosthesis or had undergone reamputation. CONCLUSIONS: Following this
      standardized surgical and rehabilitation program, prosthetic fitting was achieved
      in more than half of transtibial amputees, almost two-thirds of prosthetic
      recipients obtained good function, and the reamputation rate was low. Comparison
      with outcomes of alternative strategies is needed.

PMID- 20134309
TI  - Pellegrini-stieda disease in a patient with cauda equina syndrome.

PMID- 20134311
TI  - Edward D. Churchill as a combat consultant: lessons for the senior visiting
      surgeons and today's military medical corps.
AB  - In World War II, Edward D. Churchill volunteered as a combat consultant. In this
      role, he mentored many junior surgeons and challenged the Army leadership to
      treat hemorrhagic shock with blood rather than plasma. These lessons have
      continued relevance for today's Senior Visiting Surgeons and our military medical
      corps.

PMID- 20134312
TI  - Factors associated with septic complications after restorative proctocolectomy.
AB  - OBJECTIVE: Few studies have evaluated factors that may be associated with the
      development of septic complications after restorative proctocolectomy. Therefore,
      the aim of this study is to evaluate preoperative and operative factors that
      might be associated with septic complications after restorative proctocolectomy.
      METHODS: Patients developing abdominal and pelvic septic complications after
      restorative proctocolectomy were identified from a prospective database. Patients
      with subclinical leaks and ileostomy closure leak were not included in the septic
      complication group. A multivariable logistic regression model for sepsis was
      constructed using a forward stepwise selection with entry criterion of P < 0.05.
      RESULTS: From 1983 to 2007, 3233 patients (56% male) were included in the
      database. Eight-four percent (2597) of patients underwent proximal diversion. Two
      hundred patients (6.2%) developed septic complications within 3 months of
      restorative proctocolectomy or within 3 months of ileostomy closure. On
      multivariate analysis, body mass index > 30 (P = 0.02, OR = 1.77), final
      pathologic diagnosis of ulcerative/indeterminate colitis (P = 0.02, OR = 2) or
      Crohn's disease (P = 0.02, OR = 3.6), intraoperative (P = 0.02, OR = 1.6), and
      postoperative transfusions (P = 0.01, OR = 1.9) were all independently associated
      with septic complications. We also demonstrated an independent association among
      individual surgeons (P = 0.04) with decreased septic complications. CONCLUSIONS:
      Body mass index greater than 30, final pathologic diagnosis of
      ulcerative/indeterminate colitis or Crohn's disease, intraoperative and
      postoperative transfusions, and surgeon were all independent factors associated
      with septic complications after restorative proctocolectomy.

PMID- 20134313
TI  - Submaximal cardiopulmonary exercise testing predicts complications and hospital
      length of stay in patients undergoing major elective surgery.
AB  - OBJECTIVE: To investigate the null hypothesis that an objective, noninvasive
      technique of measuring cardiorespiratory reserve, does not improve the
      preoperative assessment of patient risk of postoperative complications, when
      compared with a standard questionnaire-based assessment of functional capacity.
      SUMMARY BACKGROUND DATA: Postoperative complications may be increased in patients
      with reduced cardiorespiratory function. Activity questionnaires are subjective,
      whereas cardiopulmonary exercise testing (CPET) provides an objective definition
      of cardiorespiratory reserve. The use of preoperative CPET to predict
      postoperative complications is not fully defined. METHOD: CPET and an algorithm
      based activity assessment (Veterans Activity Questionnaire Index [VASI]) were
      performed on consecutive patients (n = 171) with low subjective functional
      capacity (metabolic equivalent score [METS] < 7), being assessed for major
      surgery. A morbidity survey determined postoperative day 7 complications.
      Logistic regression defined independent predictors of complication group.
      Receiver-operating curve (ROC) analysis defined the predictive value of CPET to
      outcome. P < 0.05 value demonstrated significance. RESULTS: Objective
      cardiorespiratory reserve did not differ between operated (n = 116) and
      nonoperated patients (n = 55). Median complication rate on postoperative day 7
      was 1. Patients with >1 complication had an increase in hospital LOS compared to
      the group with < or =1 complication (26 vs. 10 days; P < 0.001). Anaerobic
      threshold (AT) was higher in the group with < or =1 complication (11.9 vs. 9.1
      mL/kg/min; P = 0.001) and demonstrated high accuracy (AUC = 0.85), sensitivity
      (88%), and specificity (79%), at an optimum AT of 10.1 mL/kg/min (defined by the
      furthest left point on the ROC curve). AT, VASI, and surgical reintervention were
      independent predictors of complication group. Preoperative AT significantly
      improved outcome prediction when compared with the use of VASI alone. CONCLUSION:
      An objective measure of cardiorespiratory reserve was an independent predictor of
      a major surgical group with increased postoperative complications and hospital
      LOS. AT measurement significantly improved outcome prediction compared with an
      algorithm-based activity assessment.

PMID- 20134314
TI  - Circulating microRNAs as novel minimally invasive biomarkers for breast cancer.
AB  - OBJECTIVE: The development of clinically validated biomarkers for cancer has
      remained an insurmountable task despite other advances in the field of cancer
      molecular biology. Mi(cro)RNAs have many characteristics of an ideal biomarker
      most notably their inherent stability and resilience. Recent blood-based miRNA
      profiling studies, reporting their presence in serum and plasma, have generated
      the concept that circulating miRNAs hold much potential as novel noninvasive
      biomarkers for cancer and other disease processes. The objective of this study
      was to investigate the potential of circulating microRNAs as novel breast cancer
      biomarkers. METHODS: Using a novel approach to extract miRNAs from the
      circulation followed by real-time quantitative polymerase chain reaction
      analysis, levels of a panel of 7 candidate miRNAs were quantified in tissue and
      blood specimens of 148 patients with breast cancer and 44 age-matched and disease
      free control individuals. RESULTS: We report that cancer-specific miRNAs were
      detected and significantly altered in the circulation of breast cancer patients,
      and that increased systemic miR-195 levels in breast cancer patients were
      reflected in breast tumors. Furthermore, we identified that circulating levels of
      miR-195 and let-7a decreased in cancer patients postoperatively, to levels
      comparable with control subjects, following curative tumor resection. Finally, we
      found that specific circulating miRNAs correlated with certain
      clinicopathological variables, namely nodal status and estrogen receptor status.
      CONCLUSION: These findings suggest that systemic miRNAs have potential use as
      novel breast cancer biomarkers and may prove useful in clinical management during
      the perioperative period.

PMID- 20134315
TI  - Serum CA19-9 alterations during preoperative gemcitabine-based chemoradiation
      therapy for resectable invasive ductal carcinoma of the pancreas as an indicator
      for therapeutic selection and survival.
AB  - OBJECTIVE: To evaluate serum CA19-9 alterations during preoperative gemcitabine
      based chemoradiation therapy (CRT) for resectable pancreatic cancer (PC) in the
      earlier identification of patients who are likely to benefit from subsequent
      resection. SUMMARY BACKGROUND DATA: One of the advantages of the preoperative CRT
      strategy for patients with advanced PC is that undetectable systemic disease may
      be revealed during preoperative CRT, thus avoiding unnecessary surgery. Serum
      CA19-9 has been evaluated as a predictive indicator of the treatment efficacy and
      outcome in various clinical settings. METHODS: We retrospectively reviewed 64
      consecutive patients with resectable PC (at diagnosis) who received preoperative
      CRT at our hospital between 2002 and 2008. Patients were divided into 2 groups
      (efficacy grouping) to evaluate the efficacy of preoperative CRT according to the
      clinical course. Group A included patients who were unable to receive the
      subsequent resection due to the development of unresectable factors during
      preoperative CRT and those who received the subsequent resection but developed
      recurrent disease within 6 months after surgery; group B included patients who
      received the subsequent resection and survived without recurrences for more than
      6 months after surgery. We developed a new classification utilizing pretreatment
      CA19-9 and proportional alteration of CA19-9 2 months after the initiation of
      treatment. The categories were defined as: I (increased), MD (modestly
      decreased), and SD (substantially decreased). Clinicopathological variables and
      CA19-9 alteration status were correlated with the efficacy grouping and overall
      survival. RESULTS: All of the category I patients were included in group A, 93.5%
      of the category SD patients in group B, and approximately half of the category MD
      patients in group A. CA19-9 alteration status was a single independent variable
      associated with efficacy grouping and overall patient survival, with the 1-year
      survival rate of category I patients, and the 4-year survival rate of category MD
      and SD patients being 22.2%, 34.1%, and 58.9%, respectively. CONCLUSIONS: CA19-9
      alteration status is useful in identifying those who will benefit from the
      preoperative CRT and subsequent resection and those who will not; it was a
      significant predictor for patient prognosis in the setting of the preoperative
      CRT strategy for resectable PC.

PMID- 20134316
TI  - Expression of toll-like receptors 2 and 4 is upregulated during hospital
      admission in traumatic patients: lack of correlation with blunted innate immune
      responses.
AB  - BACKGROUND: There are reports with conflicting results on the expression of toll
      like receptors (TLRs) in trauma patients. In addition, these studies analyzed TLR
      expression only at patients' hospital admission but not later when complications
      usually arise. OBJECTIVES: To analyze the surface expression of TLR2 and TLR4 on
      circulating monocytes from trauma patients during the hospitalization period and
      to correlate this with cytokine production after stimulation with TLR2 and TLR4
      agonists. The phagocytic capacity of monocytes was analyzed at the same time
      points of TLR expression analysis; to correlate these molecular findings with the
      presence or absence of infections. METHODS: Prospective and observational study
      from June 2005 to June 2007. In all analysis, a control group composed of healthy
      subjects was included. RESULTS: We studied 70 trauma patients admitted to the
      intensive care unit (ICU) of a tertiary hospital, and 30 healthy volunteers.
      Blood samples were collected at hospital admission, on day 7 and 14. Forty-four
      patients (63%) developed at least one episode of infection. Monocytes from trauma
      patients expressed higher levels of TLR2 and TLR4 than monocytes from control
      subjects at all time points. Expression of TLR2 and TLR4 in monocytes from those
      patients who developed any infection was significantly lower than in those
      patients without infection but still significantly higher than in control
      subjects. Cellular responses to TLR4 agonist were impaired. Monocytes from
      traumatic patients phagocytosized less efficiently than monocytes from control
      subjects. CONCLUSIONS: These results indicate that trauma patients present a
      dysregulation of the innate immune system that persists during the first 14 days
      after hospital admission.

PMID- 20134317
TI  - Nipple areola skin-sparing mastectomy with immediate transverse rectus abdominis
      musculocutaneous flap reconstruction is an oncologically safe procedure: a single
      center study.
AB  - OBJECTIVE: The present study evaluated the oncological safety and technical
      outcomes following nipple areola skin-sparing mastectomy (NASSM), skin-sparing
      mastectomy (SSM), and mastectomy. SUMMARY BACKGROUND DATA: Cosmetic issues
      associated with breast cancer surgery are important. The original SSM technique
      included removal of the gland and the nipple areola complex (NAC). However, the
      risk of tumor involvement of the NAC has been overestimated. PATIENTS AND
      METHODS: This retrospective study included 520 patients who underwent SSM (368
      patients) or NASSM (152 patients) with immediate breast reconstruction using a
      pedicled transverse rectus abdominis musculocutaneous (TRAM) flap, and 1990
      patients who underwent a mastectomy between July 2001 and December 2006. The
      indications for NASSM were any stage, any tumor size, and any tumor areola
      distance. Briefly, the NAC was preserved when the shape, color, and palpation of
      the nipple were normal. RESULTS: The median follow-up durations for NASSM and SSM
      were 60 and 67 months, respectively. Complete nipple areola necrosis developed in
      11 (9.6%) NASSM patients. The 5-year disease-free survival rates were 89% and
      87.2% for NASSM and SSM, respectively (P = 0.695). The 5-year overall survival
      rates were similar for NASSM and SSM (97.1% and 95.8%, respectively; P = 0.669).
      Local failure occurred in 3 (2%) NASSM and 3 (0.8%) SSM patients (P = 0.27).
      There were 2 (1.3%) nipple areola recurrences in NASSM patients. The LRRs were
      similar for NASSM and mastectomy patients. CONCLUSION: NASSM with immediate
      transverse rectus abdominis musculocutaneous reconstruction is a viable surgical
      treatment in breast cancer patients in any stage. Recurrence and complication
      rates for NASSM were similar to those for standard surgical breast cancer
      treatments.

PMID- 20134318
TI  - Prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers: very low risk for
      subsequent breast cancer.
AB  - AIM: To examine the outcome of prophylactic mastectomy in a hospital-based series
      of BRCA1/2 gene mutation carriers with and without a history of breast cancer.
      PATIENTS AND METHODS: A center-based consecutive series of 254 BRCA1/2 gene
      mutation carriers that had prophylactic mastectomy after a normal surveillance
      round including breast-magnetic resonance imaging were identified. One hundred
      forty-seven asymptomatic carriers underwent bilateral mastectomy and 107
      symptomatic women had contralateral mastectomy after a mean cancer free interval
      of 3.6 years. All removed breasts were histopathologically examined. RESULTS: In
      one asymptomatic BRCA2 carrier (0.7%) an occult small invasive breast cancer was
      diagnosed, while in 6 asymptomatic carriers (4.0% BRCA1 and 4.3% BRCA2) and in 5
      symptomatic carriers (2.5% BRCA1 and 10.7% BRCA2) DCIS was detected at
      prophylactic mastectomy. No breast cancer occurred in the asymptomatic group
      after a postprophylactic follow-up period of 778 women-years. In the symptomatic
      carriers 1 invasive breast cancer was detected after 580 follow-up years. From
      age-, cohort-, and gene-specific reference data we calculated that 15 invasive
      first cancers in the asymptomatic carriers were prevented during follow-up.
      CONCLUSION: One invasive breast cancer in 147 bilateral prophylactic mastectomies
      (0.7%) was detected, this makes a sentinel node procedure redundant and
      preoperative imaging vital. The prophylactic procedure is highly effective in
      preventing invasive breast cancer in BRCA1/2 mutation carriers. Since the
      remaining risk is less than 0.2%/woman-year, continued surveillance of the
      asymptomatic carriers is not warranted.

PMID- 20134319
TI  - Effect of percutaneous thrombectomy on echocardiographic measures of myocardial
      microcirculation in elderly patients with acute myocardial infarction.
AB  - OBJECTIVES: To study the efficacy of percutaneous thrombectomy (PT) in improving
      myocardial microcirculation in elderly acute myocardial infarction (AMI)
      patients. METHODS: A total of 104 patients (> or = 65 years) with AMI and
      coronary thrombus shown by angiography were randomly divided into a group of
      percutaneous coronary intervention (PCI) (n=52) and a group of PCI plus PT
      (n=52). At 24 h and 1 week after PCI, real-time myocardial contrast
      echocardiography was performed by contrast pulse sequencing technology. Contrast
      score index, contrast defect length/left ventricle length [CDL/LVL (%)], wall
      motion score index and wall motion abnormal length/LVL (%) were calculated.
      RESULTS: At each time point, in patients treated with PCI plus PT, contrast score
      index, CDL/LVL (%), wall motion score index and wall motion abnormal length/LVL
      (%) were significantly lower than that in the PCI group. CONCLUSION: Thrombectomy
      reduces the noreflow and the extent of microvascular obstruction, thus it was a
      feasible therapy in elderly patients with AMI.

PMID- 20134320
TI  - The effects of mechanical ventilation on hepato-splanchnic perfusion.
AB  - PURPOSE OF REVIEW: Mechanical ventilation is a cornerstone of ICU treatment.
      Because of its interaction with blood flow and intra-abdominal pressure,
      mechanical ventilation has the potential to alter hepato-splanchnic perfusion,
      abdominal organ function and thereby outcome of the most critically ill patients.
      RECENT FINDINGS: Mechanical ventilation can alter hepato-splanchnic perfusion,
      but the effects are minimal (with moderate inspiratory pressures, tidal volumes,
      and positive end-expiratory pressure levels) or variable (with high ones).
      Routine nursing procedures may cause repeated episodes of inadequate hepato
      splanchnic perfusion in critically ill patients, but an association between
      perfusion and multiple organ dysfunction cannot yet be determined. Clinical
      research continues to be challenging as a result of difficulties in measuring
      hepato-splanchnic blood flow at the bedside. SUMMARY: Mechanical ventilation and
      attempts to improve oxygenation such as intratracheal suctioning and recruitment
      maneuvers, may have harmful consequences in patients with already limited
      cardiovascular reserves or deteriorated intestinal perfusion. Due to difficulties
      in assessing hepato-splanchnic perfusion, such effects are often not detected.

PMID- 20134321
TI  - Perioperative liver protection.
AB  - PURPOSE OF REVIEW: This review presents important pathophysiological alterations
      associated with impaired liver function and discusses protective perioperative
      strategies and the various anaesthetic agents recommended. RECENT FINDINGS:
      Perioperative liver impairment is a serious complication of anaesthesia and
      surgery. Unfortunately, clinicians are provided with only crude macrohaemodynamic
      monitoring devices to optimize their therapy. Technical improvements have
      revealed some complex mysteries of perioperative microcirculatory alterations and
      have disclosed a large heterogeneity between different vascular beds. The present
      review will critically discuss current clinical concepts of optimizing global
      haemodynamic variables and the often contrasting effects of vasoactive agents on
      the microcirculatory nutritional blood flow. Finally, promising protective
      experimental interventions of pharmacological or ischaemic preconditioning are
      presented and their often disillusioning transition into recent clinical trials
      is highlighted. SUMMARY: Targeted perioperative liver protection still lacks
      adequate monitoring tools and is currently based on optimization of global
      haemodynamic variables. While there is currently no evidence suggesting a
      positive effect of ischaemic preconditioning, promising experimental results of
      pharmacological preconditioning and therapeutic hypothermia require further
      evaluation in larger randomized clinical trials.

PMID- 20134322
TI  - Do guidelines change outcomes in ventilator-associated pneumonia?
AB  - PURPOSE OF REVIEW: The purpose of the study is to summarize effects of
      implementation of current and past guidelines for management and treatment of
      ventilator-associated pneumonia (VAP) on outcome of intensive care patients, with
      particular focus on etiology of VAP, pathogens prediction, appropriate empiric
      antibiotic therapy and mortality. RECENT FINDINGS: Several studies have shown
      that in patients with clinical suspicion of VAP, appropriate antibiotic therapy
      administered in a timely manner can improve survival. Guidelines for management
      and treatment of VAP have been developed to help physicians to achieve those
      goals. Implementation of guidelines into clinical practice is difficult to
      achieve and requires extensive education for healthcare personnel and translation
      of recommendations into local protocols. Studies have shown that guidelines
      implementation is associated with better outcome. However, extensive research
      needs to be undertaken in order to validate efficacy of guidelines in predicting
      etiology of pneumonia, in particular, to promptly identify multidrug-resistant
      pathogens. Only one recent report has validated the latest guidelines and called
      attention for further research to improve microbial prediction. SUMMARY:
      Guidelines implementation can improve outcomes. To achieve this goal, guidelines
      should be adapted to local microbiology, accurately predict VAP pathogens and
      help physicians to administer the most appropriate empirical antimicrobial
      therapy.

PMID- 20134323
TI  - Scope and mechanisms of obesity-related renal disease.
AB  - PURPOSE OF REVIEW: Obesity is established as an important contributor of
      increased diabetes mellitus, hypertension, and cardiovascular disease, all of
      which can promote chronic kidney disease (CKD). Recently, there is a growing
      appreciation that, even in the absence of these risks, obesity itself
      significantly increases CKD and accelerates its progression. RECENT FINDINGS:
      Experimental and clinical studies reveal that adipose tissue, especially visceral
      fat, elaborates bioactive substances that contribute to the pathophysiologic
      renal hemodynamic and structural changes leading to obesity-related nephropathy.
      Adipocytes contain all the components of the renin-angiotensin-aldosterone
      system, plasminogen activator inhibitor, as well as adipocyte-specific
      metabolites such as free fatty acids, leptin, and adiponectin, which affect renal
      function and structure. In addition, fat is infiltrated by macrophages that can
      alter their phenotype and foster a proinflammatory milieu, which advances
      pathophysiologic changes in the kidney associated with obesity. SUMMARY: Obesity
      is an independent risk factor for development and progression of renal damage.
      Although the current therapies aimed at slowing progressive renal damage include
      reduction in weight and rely on inhibition of the renin-angiotensin system, the
      approach will likely be supplemented by interventions aimed at obesity-specific
      targets including adipocyte-driven cytokines and inflammatory factors.

PMID- 20134324
TI  - Emerging epidemic of drug-resistant tuberculosis in Europe, Russia, China, South
      America and Asia: current status and global perspectives.
AB  - PURPOSE OF REVIEW: Drug resistance, particularly through multidrug-resistant
      tuberculosis (TB) and extensively drug-resistant TB strains, poses a real threat
      to TB control worldwide. Recent reports from the WHO and the International Union
      Against Tuberculosis and Lung Disease demonstrate that the emerging epidemic of
      drug-resistant TB is a global problem, although emphasis has been placed on
      several 'hot spots' because of lack of good global data. RECENT FINDINGS: The
      present article is aimed at reviewing the available information on drug-resistant
      TB with special focus on the features of the epidemic in Europe, Russia, Latin
      America, Asia and specifically China, and to discuss the global perspectives
      related to drug-resistant TB control and care. SUMMARY: Drug-resistant TB
      originates from different human errors, including misuse of anti-TB drugs and
      other reasons related to prescribers, patients and drug producers. Although there
      is an urgent need for new drugs, a sound public health approach is necessary for
      their introduction in clinical treatment settings to prevent/avoid creating
      additional resistance, as has already been observed for first and second-line
      anti-TB drugs in many settings.

PMID- 20134325
TI  - A practical rule for optimal flows for xenon anaesthesia in a semi-closed
      anaesthesia circuit.
AB  - BACKGROUND AND OBJECTIVE: Stable haemodynamics and its cardioprotective and
      neuroprotective properties favour xenon as an ideal but expensive anaesthetic
      agent. The aim of this study was to optimize a semi-closed anaesthesia circuit
      for xenon anaesthesia with respect to economics and patient safety. METHODS: A
      semi-closed nonrebreathing circuit was compared with a closed anaesthesia
      circuit. In 12 landrace pigs, we compared eight different wash-in procedures
      affecting xenon consumption. Additionally, the maintenance of anaesthesia was
      analysed with regard to minimizing xenon consumption. RESULTS: The current study
      showed that, by optimization of the electronic regulation of the wash-in
      procedure for xenon anaesthesia, the consumption of the valuable gas can be
      reduced by up to 75% in a semi-closed circuit. The additional maintenance of
      anaesthesia under low flow conditions by coupling the xenon flow to the oxygen
      consumption is the most effective way to technically reduce the amount of xenon
      needed for anaesthesia.

PMID- 20134326
TI  - Misinterpretation of a movable mass attached to the aortic valve imaged by
      transoesophageal echocardiography.

PMID- 20134327
TI  - Measures of overweight and obesity and risk of cardiovascular disease: a
      population-based study.
AB  - BACKGROUND: Although overweight and obesity are associated with cardiovascular
      disease (CVD), it is unclear which clinical measure of overweight and obesity is
      the strongest predictor of CVD, and it is unclear whether the various measures of
      overweight and obesity are indeed independent predictors of CVD. METHODS: This
      study was a prospective population-based study of 2493 Danish men and women, age
      41-72 years, without major CVD at baseline. At baseline, body mass index, waist
      circumference, hip circumference, waist-to-hip ratio (WHR), and traditional and
      new risk factors were recorded. RESULTS: Over a median follow-up of 12.6 years,
      the incidence of a combined CV event (CV death, nonfatal ischemic heart disease,
      and nonfatal stroke) amounted to 328 cases. Of the various measures of overweight
      and obesity, in Cox-proportional hazard models, adjusted for age, only WHR was
      significantly associated with incident CVD with a hazard ratio (95% confidence
      interval) in women of 2.22 (1.31-3.77; P=0.0032) in the highest compared with the
      lowest quartile, and a hazard ratio in men of 1.73 (1.12-2.66; P=0.014) in the
      highest compared with the lowest quartile. However, when adjustments were made
      for the presence of diabetes, dyslipidemia, hypertension, hyperinsulinemia, and
      inflammation, WHR was no longer significantly (P>0.41) associated with incident
      CVD. CONCLUSION: In this study, of the various measures of overweight and
      obesity, WHR was the only significant predictor of incident CVD, and the
      relationship between WHR and risk of CVD was mediated by well-known risk factors
      of CVD.

PMID- 20134328
TI  - Homozygosity mapping: one more tool in the clinical geneticist's toolbox.
AB  - Consanguinity increases the coefficient of inbreeding, which increases the
      likelihood of presence of pathogenic mutations in a homoallelic state. Although
      this is known to have an adverse outcome by increasing the risk of autosomal
      recessive disorders, this very phenomenon has also made homozygosity mapping the
      most robust gene discovery strategy in the recent history of human genetics.
      However, homozygosity mapping can also serve as an extremely powerful tool in the
      clinical genetics setting as well. In particular, this method is highly suited in
      the setting of genetically heterogeneous conditions and inborn errors of
      metabolism that require sophisticated biochemical testing that may not be readily
      available. This article is meant to highlight the clinical utility of this
      strategy using illustrative clinical examples from the author's own clinical
      genetics practice.

PMID- 20134329
TI  - Efficacy, safety, and tolerability of etravirine with and without
      darunavir/ritonavir or raltegravir in treatment-experienced patients: analysis of
      the etravirine early access program in the United States.
AB  - BACKGROUND: Etravirine, a nonnucleoside reverse transcriptase inhibitor, was
      provided through an international early access program (EAP) prior to regulatory
      approval. METHODS: The Phase III, nonrandomized, open-label EAP investigated
      etravirine 200 mg twice daily plus a background regimen (BR) in patients who had
      failed multiple antiretroviral regimens. Efficacy and safety are reported for HIV
      infected adults from the United States through week 48, including subgroups
      receiving etravirine +/- darunavir/ritonavir and/or raltegravir. RESULTS: The
      intent-to-treat population included 2578 patients; 62.4% and 56.7% of patients
      received darunavir/ritonavir and raltegravir, respectively, in their BR. At week
      48, 62.3% of patients achieved viral loads <75 copies per milliliter; responses
      across subgroups were similar. Median CD4 count increase from baseline was >100
      cells per cubic millimeter. No unexpected safety concerns emerged; serious AEs
      and deaths due to AEs, considered possibly related to etravirine, occurred in
      2.0% and 0.3% of patients, respectively. Discontinuations due to AEs were low
      overall (4.4%) and comparable across subgroups. CONCLUSIONS: Etravirine combined
      with a BR, often including other new antiretrovirals, such as darunavir/ritonavir
      and/or raltegravir, provided an effective treatment option in treatment
      experienced patients with HIV-1.

PMID- 20134330
TI  - Similar safety and efficacy of once- and twice-daily lopinavir/ritonavir tablets
      in treatment-experienced HIV-1-infected subjects at 48 weeks.
AB  - OBJECTIVES: To compare the safety and antiviral activity of once (QD) or twice
      (BID) daily lopinavir/ritonavir (LPV/r) in combination with investigator-selected
      nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in treatment
      experienced subjects. METHODS: Subjects failing treatment with HIV-1 RNA > 1000
      copies per milliliter received LPV/r tablets 800/200 mg QD (n = 300) or 400/100
      mg BID (n = 299) with investigator-chosen nucleoside/nucleotide reverse
      transcriptase inhibitors. Efficacy was determined by the intent-to-treat time to
      loss of virologic response (ITT-TLOVR) algorithm. Safety, tolerability,
      adherence, impact of baseline protease mutations on virologic response, and
      emergence of resistance on therapy were assessed. RESULTS: Demographics were
      comparable across groups. By intent-to-treat time to loss of virologic response,
      166 QD subjects (55.3%) and 155 BID subjects (51.8%) were responders at week 48
      (P = 0.413), with similar mean increases in CD4 T-cell count. QD subjects
      demonstrated better adherence than BID subjects. The occurrence of treatment
      related moderate/severe adverse events was comparable for all events except
      nausea, which was reported more frequently among BID-treated subjects. Emergence
      of new protease resistance mutations on treatment was similarly infrequent in
      both groups. CONCLUSION: LPV/r dosed QD resulted in increased treatment adherence
      and was as efficacious as BID LPV/r while providing similar safety, tolerability,
      and limited resistance evolution.

PMID- 20134331
TI  - Practical approaches to effective family intervention after brain injury.
AB  - Rehabilitation professionals have become increasingly aware that traumatic brain
      injury has a long-term adverse impact on family members as well as on survivors.
      Family members often have a critical supporting role in the recovery process, and
      researchers have identified a relationship between caregiver well-being and
      survivor outcome. Drawing from the fields of family therapy, cognitive-behavioral
      therapy, and individual psychotherapy, this article provides information to help
      clinicians effectively serve families. First, historically important and widely
      cited publications are reviewed and their implications for practice are
      discussed. Recommendations for developing successful therapeutic alliances are
      provided along with a rationale for their importance. Descriptions of common
      challenges and issues faced by families are presented along with corresponding
      therapeutic goals. Intervention principles and strategies, selectively chosen to
      help family members achieve therapeutic goals, are discussed. The article
      concludes with a presentation of ideas to help practitioners and systems of care
      more effectively help family members adjust and live fulfilling lives.

PMID- 20134332
TI  - Clinical considerations for the diagnosis of major depression after moderate to
      severe TBI.
AB  - Major depression (MD) is the most common psychiatric disorder after traumatic
      brain injury (TBI). Yet, diagnosing MD is often challenging because of cognitive,
      emotional, and somatic symptoms that overlap with TBI and other psychiatric
      disorders. Best current evidence suggests that depressed mood is characterized
      more by irritability, anger, and aggression than by sadness and tearfulness in
      persons with TBI. Rumination, self-criticism, and guilt may best differentiate
      depressed persons from nondepressed persons. Anxiety, aggression, sleep problems,
      alcohol use, lower-income levels, and poor social functioning appear to be
      primary associated factors to MD. Objective levels of injury severity,
      impairment, and functioning do not appear to be related to developing MD. The
      presence of "organic" TBI sequelae that overlap with the Diagnostic and
      Statistical Manual of Mental Disorders-Version IV MD criteria does not appear to
      lead to false-positive MD diagnoses, and anosognosia does not appear to lead to
      false-negative MD diagnoses. Only the Patient Health Questionnaire-9 and
      Neurobehavioral Functioning Inventory-Depression demonstrated evidence of
      acceptably ruling out MD in persons with TBI; the Patient Health Questionnaire-9
      had the best ability to rule in the presence of MD following TBI. Apathy,
      anxiety, dysregulation, and emotional lability require careful clinical
      consideration when making a differential diagnosis of MD in persons with TBI.
      Lastly, recommendations are provided on how clinicians can improve diagnostic
      accuracy and what future research is required to improve our understanding of MD
      in persons with TBI.

PMID- 20134333
TI  - What is community integration anyway?: defining meaning following traumatic brain
      injury.
AB  - Full community integration, or participation in society, is the ultimate goal of
      rehabilitation and of research conducted in the field of rehabilitation for
      persons with traumatic brain injury (TBI). Community integration has been
      traditionally defined by 3 main areas: employment or other productive activity,
      independent living, and social activity. However, these have not always received
      equal weighting and attention in clinical or research efforts. Significant gaps
      remain in our understanding of factors that impact community integration and in
      our ability to intervene to improve participation for persons with TBI. This
      article describes 3 main challenges for researchers and rehabilitation
      professionals. First, a comprehensive meaning of community integration is needed,
      which includes the viewpoints and preferences of persons with TBI. Second,
      cultural competence in measurement and intervention is needed. Third, a thorough
      assessment of environmental factors impacting participation is needed and should
      be incorporated into research and treatment planning.

PMID- 20134334
TI  - The traumatic brain injury model systems: history and contributions to clinical
      service and research.
AB  - The model systems (MSs) of care for traumatic brain injury (TBI) is a
      demonstration program started by the National Institute on Disability and
      Rehabilitation Research in 1987 to improve care and outcomes for individuals with
      TBI, from emergency services through life-long follow-up. Over the next 20 years,
      the program increased in size, and the emphasis shifted from demonstration to
      research. The focal point of that research is the National Data Base, a
      longitudinal database including nearly 9000 individuals who were admitted for
      inpatient acute TBI rehabilitation. In addition to preinjury, injury, acute care,
      and rehabilitation information, the database includes reports of outcomes at 1,
      2, 5, 10, 15, etc, years postinjury. The National Data Base criteria, main
      contents, and mechanisms used to improve data quantity and quality are described.
      The MSs' other research is described: local (site-specific), module, and
      collaborative, with illustrative glimpses of the content. The impact of the TBI
      MSs program, through dissemination, knowledge translation, training of clinicians
      and researchers, as well as consulting with policy makers, administrators,
      clinicians, and researchers is discussed.

PMID- 20134335
TI  - Outcome in tracheostomized patients with severe traumatic brain injury following
      implementation of a specialized multidisciplinary tracheostomy team.
AB  - OBJECTIVE: To evaluate the effect of a specialized multidisciplinary tracheostomy
      team on outcome of patients with severe traumatic brain injury (sTBI). DESIGN:
      Retrospective study with historical controls. PARTICIPANTS: Twenty-seven patients
      with sTBI tracheostomized before implementation of the tracheostomy team approach
      and 34 patients followed by the team. SETTING: A regional level 1 tertiary care
      trauma center, McGill University Health Centre-Montreal General Hospital. MAIN
      OUTCOME MEASURES: Time to decannulation, length of stay (LOS), Passy-Muir
      speaking valve use, and extended Glasgow Outcome Scale (GOS-E) scores given at
      acute care discharge. RESULTS: The groups were similar for injury severity, age,
      and premorbid health conditions. Postteam patients had a significantly shorter
      LOS (P = .025) and more of them used Passy-Muir speaking valves (P = .004).
      Furthermore, there was a trend toward decreased time to decannulation in the
      postteam group. GOS-E scores did not differ significantly between groups (P >
      .05). CONCLUSION: Implementation of the tracheostomy team appears to have had
      positive clinical benefits for this population.

PMID- 20134336
TI  - Fall risk in patients with acute psychosis.
AB  - Patients receiving acute care for the treatment of psychotic disorders are at
      risk for falling. Complex medication regimens initiated to manage psychomotor
      agitation, lability, and aggression can contribute to physiological instability
      that may not be identified easily by clinicians. This quality improvement
      initiative identified prescribing practices associated with risk for falling and
      established a simple mechanism to monitor pharmacological treatment, which
      resulted in a reduction of the fall rate from 6.0 to 0.46.

PMID- 20134337
TI  - Assessing the relationship between compliance with antidepressant therapy and
      employer costs among employees in the United States.
AB  - OBJECTIVE: To assess effects of antidepressant treatment compliance on health
      care and workplace costs. METHODS: By using workplace survey data linked to two
      employers' health care claims, employees with depression/antidepressant claims
      were categorized into noncompliant/compliant groups. Annualized costs were
      compared between compliance groups, for the employees with antidepressant use and
      a subset diagnosed with depression. RESULTS: Among antidepressant users (N =
      1224), medical costs were not statistically different for compliant versus
      noncompliant patients; drug costs were higher for compliant patients, primarily
      because of antidepressants' costs. Similar associations were observed among
      depressed patients (N = 488). Absenteeism costs were lower for compliant patients
      with antidepressant use ($3857 vs $4,907, P = 0.041) and among depressed patients
      ($3976 vs $5899, P = 0.047). Presenteeism costs were higher for depressed
      compliant patients ($19,170 vs $15,829, P = 0.011). CONCLUSIONS: Increased
      compliance with antidepressants is significantly associated with reduced
      absenteeism costs.

PMID- 20134338
TI  - How clean is "clean"? Regulations and standards for workplace clothing and
      personal protective equipment.
AB  - OBJECTIVE: To compile current regulations and advisory recommendations on
      cleanliness of worker clothing and personal protective equipment and to evaluate
      the adequacy of criteria for determining whether cleanliness has been achieved.
      METHODS: Systematic review of information provided by federal agencies (eg, OSHA,
      MSHA, and NIOSH), nongovernmental advisory bodies (eg, ACGIH, AIHA, and ANSI),
      and manufacturers of protective clothing and equipment. RESULTS: We identified an
      array of terms describing "cleanliness" and the processes for achieving
      "cleanliness" that were almost never defined in regulations and recommendations.
      We also found a general lack of criteria for determining whether cleanliness
      and/or sterility have been achieved. CONCLUSIONS: There is need to harmonize
      cleanliness-related terminology, establish best practices for equipment cleaning
      and sterilization, implement a signage systems to provide equipment-specific
      cleaning instructions, and adopt objective criteria for determining what is
      "clean."

PMID- 20134339
TI  - Subjective response to respirator type: effect of disease status and gender.
AB  - OBJECTIVE: To assess the effect of respirator type and user characteristics (eg,
      health status) on the subjective response to respirator use. METHODS: The
      subjective responses for multiple domains were evaluated in 104 volunteers
      performing work tasks in a simulated work environment. Each used a dual cartridge
      half face mask and a filtering facepiece (N95) respirator. The study population
      was recruited to include four groups (normal respiratory status, mild asthma,
      chronic obstructive pulmonary disease, or chronic rhinitis). Mixed model
      regression analyses determined the effects of respirator type, disease, gender,
      and age. RESULTS: Half face mask produced more adverse subjective response than
      the N95 for most scales. There were significant interactions such that disease
      status modified the effect of respirator type. In general, women reported greater
      adverse ratings than did men. CONCLUSIONS: The effect of respirator type depends
      on disease status. Respirator design evaluation panels should include persons
      with mild respiratory disease.

PMID- 20134340
TI  - Measures of cognitive function and work in occupationally active breast cancer
      survivors.
AB  - OBJECTIVE: This study investigated performance-based and patient-reported
      cognitive limitations on work output. METHODS: Working breast cancer survivors
      (BCS) (n = 122) and a non-cancer comparison group (NCCG; n = 113) completed
      measures of cognitive function, fatigue, distress, job stress, and work output.
      RESULTS: Distress, fatigue, and job stress were higher in the BCS group who were
      on average 3-years post-treatment. Patient-reported cognitive limitations at work
      were related to work output in BCS (memory beta = 0.29; executive function beta =
      0.26) only. Changes in work output were more responsive to changes in job stress
      and fatigue in the BCS group. CONCLUSIONS: Reports of cognitive problems at work
      should be carefully followed up.

PMID- 20134341
TI  - Increased serum levels of soluble ST2 in birch pollen atopics and individuals
      working in laboratory animal facilities.
AB  - OBJECTIVE: To investigate toll-like receptors and CD14 expression on blood cells,
      cytokine profile of blood T-helper cells and serum levels of soluble suppression
      of tumorigenicity 2 (sST2) and sCD14 in 27 symptomatic laboratory animal (LA)
      workers with positive (n = 19) or negative (n = 8) skin-prick test to LA, 12
      birch pollen atopics and 11 non-atopic controls not exposed to LA. METHODS:
      Surface markers and intracellular cytokines were measured with flow cytometry and
      sST2 and sCD14 with ELISA. RESULTS: The group who experienced symptoms when
      working with LA, with positive and negative skin-prick test to LA, had higher
      CD14 expression on monocytes compared with those allergic to birch and controls.
      Further, serum sST2 were elevated in birch atopics and in symptomatics non
      allergic to LA compared with controls. CONCLUSION: Increased CD14 expression
      found in LA workers is most likely a response to non-allergic agent exposure
      whereas ST2 seems to react to acute allergen exposure and to non-allergic stimuli
      as pathogen-associated molecular patterns.

PMID- 20134342
TI  - Reproductive outcomes among male and female workers at an aluminum smelter.
AB  - OBJECTIVES: Several adverse pregnancy outcomes were reported among female
      laboratory workers in a North American aluminum smelter. To determine whether
      these outcomes were associated with any occupational exposure at the plant, a
      cross-sectional survey was undertaken. METHODS: Rates of miscarriage, premature
      singleton birth, and major congenital anomaly occurring during employment were
      compared with a reference group comprised of all pregnancies that occurred before
      employment. RESULTS: Among female workers, the excess of congenital anomalies
      among female laboratory workers that defined the initial cluster was observed,
      but no specific pattern was found. CONCLUSIONS: On the basis of these analyses,
      the increase in congenital anomalies could not be attributed to occupational
      exposures at the smelter nor could potential exposure likely explain the diverse
      anomalies described.

PMID- 20134343
TI  - Genetic polymorphisms in metabolizing enzymes and susceptibility of chromosomal
      damage induced by vinyl chloride monomer in a Chinese worker population.
AB  - OBJECTIVE: To evaluate whether polymorphisms in metabolizing enzymes contributed
      to susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM).
      METHODS: Cytokinesis block micronucleus test was performed on 185 VCM-exposed
      workers and 41 control subjects to detect chromosomal damage in peripheral
      lymphocytes. The polymerase chain reaction and restriction fragment length
      polymorphism technique was applied to detect polymorphisms of GSTT1, GSTM1,
      GSTP1G/A, CYP2E1G/C, and CYP2D6G/C. Poisson regression analysis was performed.
      RESULTS: Sex, age, VCM exposure, GSTP1, and CYP2E1 genotype can influence
      chromosomal damage. There was a 1.51-fold increased micronucleus frequency for
      GSTP1GG genotypes individuals compared with those GSTP1AA/GA genotype individuals
      (P < 0.05), the effect of polymorphism in CYP2E1 gene was more pronounced for
      allele C compared with allele G (P < 0.05). CONCLUSIONS: Polymorphisms of
      GSTP1G/A and CYP2E1G/C, which are potential susceptibility biomarkers of
      chromosomal damage in VCM-exposed worker.

PMID- 20134344
TI  - Ocular and respiratory symptoms among lifeguards at a hotel indoor waterpark
      resort.
AB  - OBJECTIVES: To determine the cause of eye and respiratory irritation symptoms
      among lifeguards at an indoor waterpark. METHODS: Investigators 1) performed
      environmental sampling for chloramine, endotoxin, and microbials; 2) administered
      symptom questionnaires; 3) reviewed ventilation system designs; and 4) reviewed
      water chemistry. RESULTS: Airborne trichloramine concentrations were found at
      levels reported to cause irritation symptoms in other studies. Some endotoxin
      concentrations were found at levels associated with cough and fever in previous
      studies. Exposed lifeguards were significantly more likely to report work-related
      irritation symptoms than unexposed individuals. The ventilation system may not
      have provided sufficient air movement and distribution to adequately capture and
      remove air contaminants at deck level. No water microbes were detected, and water
      chemistry met state standards. CONCLUSIONS: Indoor waterparks need to control
      water chemistry and ensure adequate air movement and distribution to control air
      contaminants and reduce health symptoms.

PMID- 20134345
TI  - Perceptions of training in occupational and environmental medicine among family
      medicine residents.
AB  - OBJECTIVE: Although knowledge of occupational and environmental medicine (OEM) is
      important for effective primary health care practice, few studies have examined
      physicians' appraisals of training in OEM. We evaluated family medicine
      residents' perceptions of a 4-week rotation in OEM that combined lectures,
      worksite visits, and clinical placements. METHODS: Qualitative analysis of
      residents' rotation evaluations (n = 208) collected between 2002 and 2008.
      Subjective appraisals were compared with quantitative changes in resident
      knowledge of OEM measured by pre- and posttests. RESULTS: Residents' perceptions
      of the usefulness of the OEM rotation were grouped into three main categories:
      knowledge, experience, and skill development. Posttest scores demonstrated
      significantly improved knowledge in key OEM subject areas. CONCLUSIONS: Residents
      gained knowledge and insight regarding the possible impact of work on patients'
      health and considered the rotation highly relevant to their family medicine
      practice.

PMID- 20134346
TI  - Productivity losses among treated depressed patients relative to healthy
      controls.
AB  - OBJECTIVES: Estimate the productivity-related cost of depression in an employed
      population. METHODS: By using administrative data, annual short-term disability
      (STD) and absenteeism costs ($2005) were compared for patients with depression
      and treated with antidepressants and for a matched control group without
      depression. RESULTS: Mean annual STD costs were $1038 among treated depressed
      patients versus $325 among controls and $1685 among a subgroup of severely
      depressed treated patients versus $340 among their controls. After controlling
      for demographic and employment characteristics, treated patients with depression
      had STD costs that were $356 higher per patient and those with severe depression
      had costs that were $861 higher. The marginal impact of treated depression on
      absenteeism was $377. CONCLUSIONS: Even when depressed patients are treated with
      antidepressants, there are substantial productivity losses. Therapies that can
      better manage depression may provide opportunities for savings to employers.

PMID- 20134347
TI  - Evaluation of coumaphos exposure among tick eradication workers.
AB  - OBJECTIVE: To evaluate both the cholinesterase monitoring program and newer field
      methods of determining coumaphos exposure among tick eradication workers.
      METHODS: Measured blood cholinesterase by the Ellman and field testing methods
      and tested urine for chlorferon pre- and postshift; conducted personal air
      sampling, patch sampling of clothing, and wipe sampling of hands for coumaphos.
      RESULTS: Fifteen workers had normal plasma cholinesterase and
      acetylcholinesterase levels. No significant changes occurred pre- to postshift.
      High correlation was found between plasma cholinesterase and acetylcholinesterase
      levels by field testing and Ellman methods (r = 0.91, P < 0.01 and r = 0.63, P <
      0.01, respectively). Chlorferon levels rose 4 to 6 hours after use (P < 0.01).
      Airborne coumaphos was detected in only one sample, in a trace amount. The
      majority of patch and hand wipe samples detected coumaphos. CONCLUSIONS: Dermal
      exposure to coumaphos resulted in significant increases in urinary metabolites of
      coumaphos.

PMID- 20134348
TI  - Benzene exposure and non-Hodgkin lymphoma: a meta-analysis of epidemiologic
      studies.
AB  - OBJECTIVE: To conduct a meta-analysis of studies of benzene exposure and non
      Hodgkin lymphoma (NHL). METHODS: A total of 8 cohort and 14 case-control studies
      were analyzed. RESULTS: Meta-analysis of any benzene exposure resulted in a
      summary relative risk estimate (SRRE) of 1.02 (95% CI: 0.94 to 1.12). The SRRE
      changed minimally when only data representing the highest level of benzene
      exposure were analyzed after an a priori data extraction protocol, using
      cumulative exposure as the optimum metric (SRRE = 1.08, 95% CI: 0.93 to 1.24).
      Meta-analysis of five studies that reported results for 60 or more ppm-years of
      cumulative exposure yielded an SRRE of 1.08 (95% CI: 0.36 to 3.24). Similarly, an
      SRRE of 1.04 (95% CI: 0.96 to 1.12) for each 25 ppm-year increment of benzene
      exposure was observed. CONCLUSIONS: The results from this meta-analysis are not
      supportive of an independent association between benzene exposure and NHL.

PMID- 20134349
TI  - Cardiovascular evaluation of electronic control device exposure in law
      enforcement trainees: a multisite study.
AB  - OBJECTIVE: Occupational health risk with regard to training exercises is a
      relatively under studied domain for law enforcement officers. One potential
      health risk is exposure to electronic control devices (ECDs). METHODS: Seven
      different training facilities in six states participated. Law enforcement
      trainees (N = 118) were exposed to Taser International's (Scottsdale, AZ) X26 for
      up to 5 seconds. RESULTS: There was no evidence of cardiac or skeletal muscle
      breakdown. Exposure did not adversely affect electrocardiogram (ECG) morphology
      obtained 24 hours after exposure in 99 trainees. For two trainees with
      preexisting ECG abnormalities, ECG morphology differed in the post-ECD samples.
      CONCLUSIONS: The results from this large, multisite study suggest that, for most
      trainees, ECD exposure does not represent a significant health risk. Further
      investigation is warranted for cardiac vulnerability and potential interactions
      with ECD exposure.

PMID- 20134350
TI  - Respirator physiologic impact in persons with mild respiratory disease.
AB  - OBJECTIVE: To assess whether mild respiratory disease affects physiologic
      adaptation to respirator use. METHODS: The study compared the respiratory effects
      of dual cartridge half face mask and filtering facepeice (N95) respirators while
      performing simulated-work tasks. Subjects with mild chronic obstructive pulmonary
      disease (n = 14), asthma (n = 42), chronic rhinitis (n = 17), and normal
      respiratory status (n = 24) were studied. Mixed model regression analyses
      determined the effects of respirator type, disease status, and the respirator
      disease interactions. RESULTS: Respirator type significantly affected several
      physiologic measures. Respirator type effects differed among disease categories
      as shown by statistically significant interaction terms. Respiratory timing
      parameters were more affected than ventilatory volumes. In general, persons with
      asthma showed greater respirator-disease interactions than chronic obstructive
      pulmonary disease, rhinitis, or healthy subjects. CONCLUSIONS: The effects of
      respirator type differ according to the category of respiratory disease.

PMID- 20134351
TI  - Impaired health status, daily functioning, and work productivity in adults with
      excessive sleepiness.
AB  - OBJECTIVE: This study evaluated the effects of excessive sleepiness (ES) on
      health status, daily functioning, and work productivity. METHODS: From a survey
      performed in June to July 2006, people with or without ES in two groups (1758
      with obstructive sleep apnea, depression, narcolepsy, multiple sclerosis, or
      shift work; 1977 without these conditions) were assessed on the Work Productivity
      and the Activity Impairment Scale, Short Form-12, Medical Outcomes study 6-item
      Cognitive Function Scale, and the Toronto Hospital Alertness Test. RESULTS: ES in
      both groups was associated with highly significant impairments in health status,
      daily activities, and work productivity for all measures (P < 0.0001), except for
      absenteeism (P = 0.0400 for group A, P = 0.8360 for group B). CONCLUSIONS: ES may
      have an incremental negative impact measurable above that of obstructive sleep
      apnea, multiple sclerosis, narcolepsy, depression, or shift work.

PMID- 20134352
TI  - Compliance with a sepsis bundle and its effect on intensive care unit mortality
      in surgical septic shock patients.
AB  - BACKGROUND: The Surviving Sepsis Campaign was launched in 2002, aiming at a 25%
      reduction in mortality in sepsis during a 5-year period. We hypothesized that the
      compliance with an adapted sepsis bundle would improve intensive care unit (ICU)
      survival in a cohort of surgical septic shock patients. METHODS: A retrospective,
      observational study was performed in surgical ICUs from two University hospitals.
      Seven quality indicators were considered to study the compliance with the sepsis
      bundle in 182 patients: (1) administration of antibiotics within 6 hours from
      diagnosis of septic shock, (2) initial effective antibiotic treatment, (3)
      adequate resuscitation within 6 hours after the diagnosis of septic shock, (4)
      administration of steroids, (5) use of activated protein C, (6) glucose control,
      and (7) protective ventilation. Univariate and multivariate logistic regression
      analyses were performed to make a predictive model to study the probability of
      survival according to the number of therapeutic guidelines fulfilled and to
      adjust for other predictive factors. RESULTS: Compliance with individual
      guidelines was considered adequate in more than 60% of the cases, except in the
      case of glucose control. For all quality indicators, ICU survival was higher in
      the bundle-compliant patients. Survival (61%) was associated with the fulfilment
      of increasing number of therapeutic guidelines (odds ratio, 1.64; 95% confidence
      interval, 1.28-2.1; p < 0.001). CONCLUSIONS: In surgical septic shock patients,
      the outcome was significantly related to the number of fulfilled therapeutic
      guidelines included in a sepsis bundle.

PMID- 20134353
TI  - Concentrated pitch discrimination modulates auditory brainstem responses during
      contralateral noise exposure.
AB  - This study examined a notion that auditory discrimination is a requisite for
      attention-related modulation of the auditory brainstem response (ABR) during
      contralateral noise exposure. Given that the right ear was exposed continuously
      with white noise at an intensity of 60-80 dB sound pressure level, tone pips at
      80 dB sound pressure level were delivered to the left ear through either single
      stimulus or oddball procedures. Participants conducted reading (ignoring task)
      and counting target tones (attentive task) during stimulation. The oddball but
      not the single-stimulus procedures elicited task-related modulations in both
      early (ABR) and late (processing negativity) event-related potentials
      simultaneously. The elicitation of the attention-related ABR modulation during
      contralateral noise exposure is thus considered to require auditory
      discrimination and have the corticofugal nature evidently.

PMID- 20134354
TI  - Role of spinal p38alpha and beta MAPK in inflammatory hyperalgesia and spinal COX
      2 expression.
AB  - Pharmacological studies indicate that spinal p38 mitogen-activated protein kinase
      plays a role in the development of hyperalgesia. We investigated whether either
      the spinal isoform p38alpha or p38beta is involved in peripheral inflammation
      evoked pain state and increased expression of spinal COX-2. Using intrathecal
      antisense oligonucleotides, we show that hyperalgesia is prevented by
      downregulation of p38beta but not p38alpha, whereas increases in spinal COX-2
      protein expression at 8 hours are mediated by both p38alpha and beta isoforms.
      These data suggest that early activation of spinal p38beta isoform may affect
      acute facilitatory processing, and both p38beta and alpha isoforms mediate
      temporally delayed upregulation of spinal COX-2.

PMID- 20134355
TI  - Estradiol or fluoxetine alters depressive behavior and tryptophan hydroxylase in
      rat raphe.
AB  - The effects of 17beta-estradiol and fluoxetine on behavior of ovariectomized rats
      subjected to the forced swimming test and the expression of tryptophan
      hydroxylase (TPH) in dorsal and median raphe were investigated, respectively
      through time sampling technique of behavior scoring and immunohistochemistry.
      Both estradiol and fluoxetine increased swimming and decreased immobility in the
      forced swimming test. The forced swimming stress decreased integrated optical
      density of TPH-positive regions in dorsal and median raphe. Both estradiol and
      fluoxetine administration prevented integrated optical density of TPH-positive
      regions from being decreased by forced swimming stress. These observations
      suggest that both estradiol and fluoxetine have protective bearing on
      ovariectomized rats enduring forced swimming stress.

PMID- 20134356
TI  - Stimulus-preceding negativity is modulated by action-outcome contingency.
AB  - We investigated the relationship between action-outcome contingency and stimulus
      preceding negativity (SPN), a motivationally sensitive event-related potential.
      Neuroimaging studies have shown that insular cortex (a known source of the SPN)
      is more activated prior to rewards that are contingent on prior correct action
      than rewards that are given gratuitously. We compared two gambling tasks, one in
      which the participant attempted to guess the profitable key-press option (choice)
      and one in which rewards were simply given at random (no-choice). The SPN that
      developed in anticipation of feedback was larger in the choice condition,
      especially at right anterolateral sites. These findings suggest that the SPN
      specifically reflects the expectation of response reinforcement, rather than
      anticipatory attention toward emotionally salient stimuli.

PMID- 20134357
TI  - Hippocampal sst(1) receptors are autoreceptors and do not affect seizures in
      rats.
AB  - Somatostatin-14 (SRIF-14) exerts anticonvulsive effects in several rat seizure
      models, generally attributed to sst(2) receptor activation. Whereas sst(1)
      immunoreactivity has been localized to both polymorphic interneurons and
      principal cells in the rat hippocampus, its potential role as an inhibitory
      autoreceptor or as a receptor involved in mediating anticonvulsive actions
      remains unknown. We showed that intrahippocampal administration of the sst(1)
      antagonist SRA880 (1 microM) induced a robust increase in hippocampal SST-14
      levels without affecting gamma-aminobutyric acid levels in conscious rats,
      indicating that the sst(1) receptor acts as an inhibitory autoreceptor. SRA880
      did not affect seizure severity and did not reverse the anticonvulsive action of
      SRIF-14 (1 microM) against pilocarpine-induced seizures, suggesting that
      hippocampal sst(1) receptors are not involved in the anticonvulsive effects of
      SRIF-14.

PMID- 20134358
TI  - 99mTc-WBC scintigraphy with SPECT/CT in the evaluation of arterial graft
      infection.
AB  - OBJECTIVE: The goals of our study were to retrospectively review our experience
      in using Tc-white blood cell (WBC) single-photon emission computed
      tomography/computed tomography (SPECT/CT) imaging in the evaluation of possible
      arterial graft infection and to attempt to establish objective criteria for
      assessment. METHODS: Eleven Tc-WBC SPECT/CT studies performed for the evaluation
      of clinically suspected arterial graft infection were retrospectively reviewed
      and compared with reference outcomes. In an attempt to define objective criteria
      for interpretation, comparison was also made with background liver and bone
      marrow activity. RESULTS: When compared with reference outcomes, the subjective
      scan interpretations showed 6 of 11 true positives (TP), 4 of 11 true negatives
      (TN), and 1 of 11 false positive (FP). Using the liver as a comparator resulted
      in 4 of 10 TP, 5 of 10 TN, and 1 of 10 FN. Using the bone marrow as a comparator
      resulted in 3 of 10 TP, 5 of 10 TN, and 2 of 10 FN. In one patient neither the
      liver nor the bone marrow was in the field of view. CONCLUSION: These findings
      suggest a high accuracy for Tc-WBC SPECT/CT in assessing clinically suspected
      arterial graft infection. Furthermore, the liver may be the best objective
      comparator for standardized interpretation.

PMID- 20134359
TI  - The interaction between respiratory viruses and pathogenic bacteria in the upper
      respiratory tract of asymptomatic Aboriginal and non-Aboriginal children.
AB  - BACKGROUND: Associations between respiratory viruses and the bacterial pathogens
      Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis may
      be important in the pathogenesis of otitis media (OM). However, data on
      asymptomatic identification rates of respiratory viruses are limited,
      particularly in Indigenous populations, who suffer a high burden of OM. METHODS:
      We describe the identification of respiratory viruses alone and in combination
      with pathogenic OM bacteria in 1006 nasopharyngeal aspirates collected from
      asymptomatic Aboriginal and non-Aboriginal children in a longitudinal community
      based cohort study in rural Western Australia. RESULTS: Viruses were identified
      in 42% of samples from Aboriginal and 32% from non-Aboriginal children.
      Rhinoviruses were the most frequently identified virus with higher identification
      rates in Aboriginal (23.6%) than non-Aboriginal children (16.5%; P = 0.003).
      Rhinoviruses were associated with H. influenzae (odds ratio [OR], 2.24; 95% CI,
      1.24-4.07 for Aboriginal children) and M. catarrhalis (OR, 1.94; 95% CI, 1.05
      3.57 for Aboriginal children). Adenoviruses were positively associated with H.
      influenzae in Aboriginal children (OR, 3.30; 95% CI, 1.19-9.09) and M.
      catarrhalis in non-Aboriginal children (OR, 5.75; 95% CI, 1.74-19.23), but
      negatively associated with S. pneumoniae in Aboriginal children (OR, 0.39; 95%
      CI, 0.18-0.84). CONCLUSIONS: We found a high identification rate of rhinoviruses
      and adenoviruses in asymptomatic children. The associations between these viruses
      and OM bacteria have implications for preventive strategies targeted at specific
      pathogens.

PMID- 20134360
TI  - A prospective analysis of bony versus soft-tissue reconstruction for posterior
      mandibular defects.
AB  - BACKGROUND: Although reconstruction of anterior mandibular oncologic defects with
      bony free flaps is considered the standard method of treatment, the optimal
      reconstruction of posterior defects is controversial. The authors' goal was to
      compare outcomes using either a vascularized bone flap or a soft-tissue free flap
      for posterior mandibular reconstruction. METHODS: Data were collected
      prospectively on 74 patients undergoing posterior mandibular resection including
      the condyle. RESULTS: Twenty-four patients underwent vascularized bone flap
      reconstruction and 50 patients underwent soft-tissue free flap reconstruction.
      Patients undergoing vascularized bone flap reconstruction were significantly
      younger than those undergoing soft-tissue free flap reconstruction (47 versus 62
      years, respectively; p = 0.0001) and had a lower American Society of
      Anesthesiologists class (2.6 versus 3.1, respectively; p = 0.001). There were no
      significant differences in total operative time, intensive care unit stay, or
      hospital stay. The complication rate was 33 percent for patients receiving
      vascularized bone flap reconstructions and 38 percent for patients receiving soft
      tissue free flap reconstruction (p = 0.70). Mouth opening averaged 39.8 mm for
      patients with vascularized bone flap reconstructions and 46.4 mm for patients
      with soft-tissue free flap reconstructions (p = 0.09). Jaw deviation toward the
      resection side averaged 1.2 mm for vascularized bone flap reconstructions and 5.3
      mm for soft-tissue free flap reconstructions (p = 0.02). There was no significant
      difference in the type of mechanical diet tolerated by either group (p = 0.83).
      CONCLUSIONS: With careful selection, good reconstructive results after posterior
      mandibular resection can be achieved with vascularized bone flap or soft-tissue
      free flaps. In appropriate candidates, vascularized bone flap reconstruction may
      result in better postoperative occlusion.

PMID- 20134362
TI  - Immediate soft-tissue reconstruction for complex defects of the spine following
      surgery for spinal neoplasms.
AB  - BACKGROUND: Innovations in surgical approaches and instrumentation for spinal
      stabilization have allowed radical resections of advanced spinal neoplasms.
      Wounds that expose instrumentation and vital neural structures can have
      devastating consequences. In this study, the authors present a paradigm shift in
      the way complex wounds of the spine are managed, where immediate, prophylactic
      muscle-flap reconstruction is provided, particularly for those patients
      identified to be at high risk for wound-healing complications. The purpose of
      this study was to determine the outcomes of this new prophylactic approach to
      managing complex spine wounds. METHODS: The authors retrospectively reviewed
      spine tumor patients who underwent immediate reconstruction for complex wounds of
      the spine from 2004 to 2008. From the prospectively maintained database and
      medical records, the authors collected information regarding reconstructive
      methods, defect location, patient conditions, complications, and revision
      operations. RESULTS: Of the 52 patients, 34 (65 percent) had undergone prior
      irradiation, 17 (33 percent) had undergone prior surgery to the spine, and 44 (85
      percent) had undergone spine instrumentation. Overall, six patients (12 percent)
      had major complications that required surgical intervention. The instrumentation
      did not need to be removed in any of the patients. All patients had a closed
      wound at their last clinic visit. CONCLUSIONS: Complex wounds of the spine
      benefit from immediate prophylactic reconstruction with muscle flaps. This
      approach has a high rate of success in achieving a stable, closed wound while
      minimizing major wound complications, even in the presence of adverse conditions
      such as prior irradiation, prior operations, and the presence of hardware.

PMID- 20134361
TI  - Retinoic acid enhances osteogenesis in cranial suture-derived mesenchymal cells:
      potential mechanisms of retinoid-induced craniosynostosis.
AB  - BACKGROUND: In utero retinoid exposure results in numerous craniofacial
      malformations, including craniosynostosis. Although many malformations associated
      with retinoic acid syndrome are associated with neural crest defects, the
      specific mechanisms of retinoid-induced craniosynostosis remain unclear. The
      authors used the culture of mouse cranial suture-derived mesenchymal cells to
      probe the potential cellular mechanisms of this teratogen to better elucidate
      mechanisms of retinoid-induced suture fusion. METHODS: Genes associated with
      retinoid signaling were assayed in fusing (posterofrontal) and patent (sagittal,
      coronal) sutures by quantitative real-time polymerase chain reaction. Cultures of
      mouse suture-derived mesenchymal cells from the posterofrontal suture were
      established from 4-day-old mice. Cells were cultured with all-trans retinoic acid
      (1 and 5 muM). Proliferation, osteogenic differentiation, and specific gene
      expression were assessed. RESULTS: Mouse sutures were found to express genes
      necessary for retinoic acid synthesis, binding, and signal transduction,
      demonstrated by quantitative real-time polymerase chain reaction (Raldh1, Raldh2,
      Raldh3, and Rbp4). These genes were not found to be differentially expressed in
      fusing as compared with patent cranial sutures in vivo. Addition of retinoic acid
      enhanced the osteogenic differentiation of suture-derived mesenchymal cells in
      vitro, including up-regulation of alkaline phosphatase activity and Runx2
      expression. Contemporaneously, cellular proliferation was repressed, as shown by
      proliferative cell nuclear antigen expression. The pro-osteogenic effect of
      retinoic acid was accompanied by increased gene expression of several hedgehog
      and bone morphogenetic protein ligands. CONCLUSIONS: Retinoic acid represses
      proliferation and enhances osteogenic differentiation of suture-derived
      mesenchymal cells. These in vitro data suggest that retinoid exposure may lead to
      premature cranial suture fusion by means of enhanced osteogenesis and hedgehog
      and bone morphogenetic protein signaling.

PMID- 20134363
TI  - Evaluation of subciliary incision used in blowout fracture treatment: pretarsal
      flattening after lower eyelid surgery.
AB  - BACKGROUND: The skin-muscle flap has been widely used for many years in eyelid
      surgery. However, lid retraction and pretarsal flattening are considerable
      cosmetic complications. Furthermore, it has also been reported that damage of the
      zygomatic branch reduces muscle tone and contributes to the development of
      various complications. The authors investigated whether denervation of the
      zygomatic branch affects lid retraction and pretarsal flattening in pure blowout
      fractures. METHODS: The authors studied 286 unilateral pure blowout fracture
      patients from January of 2005 to December of 2006. Mean patient age was 35.6
      years (range, 9 to 72 years), the male-to-female ratio was 1.7:1, and the mean
      follow-up period was 28 months (range, 19 to 40 months). No patients had
      undergone eyelid surgery previously. Eyelid tone was evaluated using the snap
      test and the lid distraction test. Pretarsal shape was evaluated using
      photographs, which were presented to three plastic surgeons and six medical
      students unaware of surgical information. RESULTS: Increased laxity was found in
      only 13 patients (4.5 percent). When viewing photographic comparisons, medical
      students noticed visible scars in 10 patients (3.5 percent), pretarsal flattening
      in eight patients (2.8 percent), and eyelid malposition in eight patients (2.8
      percent), whereas the plastic surgeons noticed visible scars in 10 cases (3.5
      percent), pretarsal flattening in 10 cases (3.5 percent), and eyelid malposition
      in nine cases (3.1 percent). CONCLUSIONS: In this study, it can be inferred that
      pretarsal flattening may not be a problem associated with the skin-muscle flap
      itself accompanying denervation of the zygomatic branch. Instead, technical
      expertise, conservation of the buccal branch, and meticulous hemostasis are
      essential for the prevention of complications.

PMID- 20134364
TI  - The Radial Artery Pedicle Perforator Flap:  Vascular Analysis and Clinical
      Implications.
AB  - BACKGROUND: The purpose of this study was to determine the location, size, and
      vascular territory of the radial artery cutaneous perforators. METHODS: Twenty
      six human cadaveric forearms were dissected. All cutaneous radial artery
      perforators were analyzed for total number, orientation, location, and external
      diameter. A cluster analysis was performed to determine the overall distribution
      of perforators. The cutaneous territory of a distally based pedicled perforator
      flap was determined using methylene blue injection and three-dimensional computed
      tomographic angiography in five flaps. RESULTS: Six hundred thirty-nine
      perforators (399 perforators smaller than 0.5 mm compared with 240 perforators
      0.5 mm or larger) were dissected in 26 forearms. Of the 639 radial artery
      perforators dissected, 328 (51 percent) were radially distributed and 311 (49
      percent) were ulnarly distributed. There are two main clusters of clinically
      relevant perforators at a relative distance of 17.6 percent and 61.7 percent
      along the radial styloid-to-lateral epicondyle interval. In all cases, two or
      more perforators were found within 2 cm proximal to the styloid. Dye injection of
      the most dominant distally based perforators revealed a cutaneous territory
      ranging from 104 cm2 to 333 cm2. The case presented is of a patient with a dorsal
      hand defect, which was resurfaced with a pedicled perforator flap based on a
      distal perforator proximal to the radial styloid. CONCLUSIONS: There are two main
      clusters of clinically significant radial artery perforators. Increased knowledge
      of size, location, and cutaneous territory of the radial artery perforators can
      lead to expanded use of the radial artery forearmflap based on cutaneous
      perforators alone, without sacrificing the radial artery.

PMID- 20134367
TI  - Familial isolated primary hyperparathyroidism with double adenoma.
AB  - Familial hyperparathyroidism includes the diagnoses of multiple endocrine
      neoplasia type 1, type 2A, and familial isolated primary hyperparathyroidism.
      Familial isolated primary hyperparathyroidism is a rare, distinct form of
      familial primary hyperparathyroidism, mainly due to four-gland hyperplasia or
      single-gland adenoma. We describe our success in treating a 24-year-old woman
      with familial isolated primary hyperparathyroidism with resection of double
      adenoma, using the guide of intraoperative parathyroid hormone (PTH) monitoring.
      Familial isolated primary hyperparathyroidism usually presents with four-gland
      hyperplasia or single-gland adenoma. However, double adenoma should be considered
      in the differential diagnosis. Using intraoperative parathyroid hormone levels
      and minimal-access surgery in familial isolated primary hyperparathyroidism may
      be promising.

PMID- 20134368
TI  - Considering global vaccination against Helicobacter pylori.

PMID- 20134369
TI  - Fantasy-land, reality-land, and guns.

PMID- 20134370
TI  - Diagnosing of Clostridium difficile colitis.

PMID- 20134371
TI  - The activity of carotidynia syndrome is correlated with the soluble intracellular
      adhesion molecule-1 (sICAM-1) level.

PMID- 20134372
TI  - Effect of Helicobacter pylori eradication on insulin resistance, serum lipids and
      low-grade inflammation.
AB  - BACKGROUND/AIM: Many studies have revealed a close relationship between
      Helicobacter pylori (HP) infection and insulin resistance. The aim of this study
      was to investigate the effects of HP eradication on insulin resistance, serum
      lipids and low-grade inflammation. MATERIALS AND METHODS: This was a prospective,
      open-label, single-center study which consisted of 159 patients. The patients
      with HP infection received a 14-day sequential regimen. A HOMA-IR (homeostasis
      model assessment of insulin resistance) level was used to assess insulin
      resistance. RESULTS: Eighty-eight patients with HP infection and seventy-one
      patients without HP infection were studied. HOMA-IR, total cholesterol (TC),
      triglyceride (TG), LDL cholesterol (LDL-C) and C reactive protein (CRP) levels
      were significantly higher and HDL-cholesterol (HDL-C) levels were significantly
      lower in patients with HP infection compared to the patients without HP infection
      (P<0.05). The HP eradication rates with a sequential regimen in dyspeptic
      patients were 53.4%. Six weeks after the end of eradication therapy, the mean
      fasting insulin, HOMA-IR, TC, TG, LDL-C, and CRP levels in patients with
      successful eradication were significantly decreased from the pretreatment levels
      (P<0.05) and HDL-C level was significantly increased from the pretreatment levels
      (P<0.05). The mean fasting insulin, HOMA-IR, TC, TG, LDL-C, CRP levels and HDL-C
      levels in patients with unsuccessful eradication were not significantly changed
      from pretreatment levels (P<0.05). CONCLUSION: This study showed beneficial
      effects of HP eradication on insulin resistance, atherogenic lipid abnormalities
      and low-grade inflammation. The results suggest that HP eradication may prevent
      coronary artery disease and metabolic syndrome.

PMID- 20134373
TI  - The value of neopterin and procalcitonin in patients with sepsis.
AB  - OBJECTIVE: Neopterin (NT) is a compound of low molecule-based pteridine. It is
      secreted by macrophages as a response to the stimulation of cytokines such as
      interferon-gamma, interferon-1beta, tumor necrosis factor alpha or bacteria
      compounds such as lipopolysaccharides. Procalcitonin (PCT) levels may increase in
      the course of bacterial, parasitic, and fungal infections. Therefore, it can be
      used for the differential diagnosis of the infection, especially in cases of
      serious inflammation. In this study, the role of NT, and PCT in sepsis as a
      prognostic factor, and the relationship between the two parameters are examined.
      METHODS: From November 1, 2005 through December 31, 2005, fifty patients with
      sepsis admitted to the Department of the Infectious Diseases and Clinical
      Microbiology and/or Department of Anaesthesiology and Reanimation were enrolled
      in the study. Patients were divided in two subgroups according to their survival:
      group I (n=23) nonsurviving patients and group II (n=27) surviving patients.
      RESULTS: Serum NT levels have been found to be increased in group I (median: 15
      ng/mL, range: 2-69) when compared to group II (median: 5 ng/mL, range: 2-130).
      The difference was statistically significant (P=0.03). Other laboratory
      parameters and PCT levels (group I median: 0.13; group II median: 0.08; P<0.05)
      were not different between the two groups. CONCLUSIONS: NT was found to be a
      prognostic factor in patients with sepsis.

PMID- 20134374
TI  - Intrathecal sufentanil for intraoperative and postesophagectomy pain relief.
AB  - OBJECTIVES: The present study compares the analgesic properties of intrathecal
      (IT group) and intravenous (IV group) sufentanil in postoperative pain relief.
      METHODS: This randomized, single blinded study was performed on patients awaiting
      transhiatal esophagectomy. The patients were randomly allocated to receive
      sufentanil intrathecally or intravenously. Sufentanil consumption during the
      operation, pain score following the operation based on visual analog scale (VAS)
      and the morphine requirement for postoperative analgesia were assessed during the
      first 24 hours. RESULTS: Fifty patients were divided in two groups. During the
      operation, the opioid requirement was higher in the IV group, whereas the
      morphine requirement during the first 24 hours after the operation was the same
      in both groups. The duration of effective postoperative analgesia was longer in
      patients in the IT group. VAS pain scores were significantly lower during the
      first 2 hours postoperatively in the IT group. The incidence of side effects such
      as nausea, vomiting, headache and respiratory depression was infrequent in both
      groups. CONCLUSIONS: Preoperative IT sufentanil can be used as a booster to
      achieve rapid and effective analgesia not only during the operation but also
      during the immediate postoperative period.

PMID- 20134375
TI  - Management of chronic kidney disease: what is the evidence?
AB  - Chronic kidney disease (CKD) is a strong risk factor for cardiovascular events
      and death. Hypertension, dyslipidemia, anemia, vascular calcification, and
      secondary hyperparathyroidism have all been implicated in the pathogenesis of
      cardiovascular disease associated with CKD. Numerous trials have been performed
      assessing the effects of modifying these risk factors on cardiovascular events
      and on the progression to end-stage renal disease. Many guidelines have been
      issued. In this article we review the guidelines and the strength of evidence
      supporting them. Specifically, we discuss blood pressure goals for patients with
      CKD, the role of renin-angiotensin system blocking agents for blood pressure
      control and proteinuria reduction, and the evidence for treatment recommendations
      of dyslipidemia. We review the trials addressing risks and benefits of different
      hemoglobin targets for treatment of anemia with erythropoietin. The use of
      phosphate-binding drugs to prevent and treat secondary hyperparathyroidism is
      likely beneficial, but few data support the use of vitamin D compounds.
      Supplementation with sodium bicarbonate may be an inexpensive treatment to retard
      progression to end-stage renal disease. The article concludes with a discussion
      of the case vignette presented in the previous article.

PMID- 20134376
TI  - Cinacalcet in the treatment of intractable hypercalcemia following two neck
      exploration surgeries for primary hyperparathyroidism.
AB  - Primary hyperparathyroidism is commonly due to a single, sporadic parathyroid
      adenoma, and surgery is considered the treatment of choice based on guidelines
      established by the National Institutes of Health consensus panel. While there is
      no established medical therapy for this condition, pharmacotherapy with agents
      such as cinacalcet could be a preferred alternative in a subset of patients with
      persistent hypercalcemia after one or more surgical interventions.

PMID- 20134377
TI  - Radius fracture from an electrical injury involving an electric guitar.
AB  - Electrical injury ranges widely from simple shock and mild burns to more
      extensive superficial injury, internal injury, and mortality. Bony fracture from
      electrically-induced tetanic muscle contraction is a rare but recognized injury.
      We report the case of a 14-year-old boy who suffered a minor burn and radius
      fracture related to an electrical injury involving his electric guitar. An
      interesting pattern is emerging from available case reports of similar injuries.

PMID- 20134378
TI  - Overuse of acid suppression therapy in hospitalized patients.
AB  - BACKGROUND: Acid suppression therapy (AST) is one of the most commonly prescribed
      classes of medications in hospitalized patients. Multiple studies have shown that
      AST is overused during inpatient admissions. However, minimal data is available
      regarding the frequency and patient characteristics of those discharged on
      unnecessary AST. The aims of the study were to examine administration of AST on
      admission, to characterize the patient population discharged on unnecessary AST
      and to determine predictive factors for inappropriate administration of AST in
      hospitalized patients. METHODS: A retrospective chart review of randomly selected
      patients admitted to the general medicine service at University of Florida Health
      Science Center/Jacksonville from August to October 2006 for appropriateness of
      AST was done. The admitting diagnosis, indications for starting AST, type of AST
      used, and discharge on these medications was recorded on a case by case basis.
      RESULTS: Seventy percent of patients were started on AST on admission. Of these,
      73% were unnecessary. Stress ulcers prophylaxis in low risk patients or the
      concomitant use of ulcerogenic drugs motivated initiation of therapy most
      frequently. Sixty nine percent of patients started on inappropriate AST were
      discharged on the same regimen. Admitting diagnosis, age of patient, length of
      stay, or concomitant use of ulcerogenic drugs did not predict continuation of
      unnecessary AST at discharge. CONCLUSION: AST is overused in hospitalized
      patients. This primarily occurred in low risk patients and was compounded by
      continuation at discharge. This significantly increases cost to the health care
      system and the risk of drug interactions.

PMID- 20134379
TI  - Reparative change with extensive squamous metaplasia: a potential diagnostic
      pitfall on thyroid aspiration.
AB  - Squamous metaplasia and cystic change can appear in the thyroid and mimic a
      variety of lesions. In this report, a patient with two dominant left thyroid
      nodules underwent fine needle aspiration (FNA) biopsy for each nodule. One of the
      nodules was diagnosed as consistent with papillary carcinoma and the other as
      suspicious for papillary carcinoma. Subsequent near total thyroidectomy revealed
      both lesions to be part of a goiter with extensive squamous metaplasia. This
      article discusses a potential pitfall in the interpretation of fine needle
      aspirates of squamous metaplastic cells in the thyroid.

PMID- 20134380
TI  - Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy.
AB  - Chronic metformin use results in vitamin B12 deficiency in 30% of patients.
      Exhaustion of vitamin B12 stores usually occurs after twelve to fifteen years of
      absolute vitamin B12 deficiency. Metformin has been available in the United
      States for approximately fifteen years. Vitamin B12 deficiency, which may present
      without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic
      neuropathy, although the clinical findings are usually different. Failure to
      diagnose the cause of the neuropathy will result in progression of central and/or
      peripheral neuronal damage which can be arrested but not reversed with vitamin
      B12 replacement. To my knowledge, this is the first report of metformin-induced
      vitamin B12 deficiency causing neuropathy.

PMID- 20134381
TI  - Macrodactylia fibrolipomatosis presenting as a small bowel obstruction.
AB  - A patient presented with progressive abdominal distention, discomfort, nausea,
      vomiting, and constipation. The patient also had congenital macrodactyly of the
      third, fourth, and fifth digits of the left hand. He [corrected] was diagnosed
      with macrodactylia fibrolipomatosis with multiple small bowel lipomas and
      complete small bowel obstruction. Macrodactylia fibrolipomatosis is a rare
      condition characterized by benign fibrofatty infiltration involving the soft
      tissues of the distal arm or leg with associated dactylomegaly of the associated
      digits. This patient had a rare presentation that included extensive small bowel
      lipomatosis.

PMID- 20134382
TI  - The amount of comorbidities as a single parameter has no effect in predicting the
      outcome in appendicitis patients older than 60 years.
AB  - BACKGROUND: Retrospective analysis of acute appendicitis patients older than 60
      and statistical evaluation of the association between the accompanying illnesses,
      severity of peritonitis, morbidity, and mortality rates. INTRODUCTION: Although
      acute appendicitis is not frequent among aged populations, accompanying
      comorbidities of the geriatric patients are always fear factors before an
      emergency abdominal surgery even for acute appendicitis. METHODS: The data of the
      27 patients older than 60 years who underwent appendectomy were retrospectively
      analyzed. The patients were grouped according to the total number of their
      comorbidities, Mannheim peritonitis index scores, and the period between the
      onset of abdominal pain and the admission to the hospital. RESULTS: The mean age
      of the patients was 73 years. The morbidity and mortality rates were
      statistically significantly higher in perforated cases. The comparison of
      patients with <or=1 comorbidity with patients with >or=2 comorbidities did not
      show any statistical difference in morbidity and mortality. The sensitivity,
      specificity, positive predictive value, and negative predictive values for
      mortality in geriatric acute appendicitis patients with Mannheim peritonitis
      index scores greater than 26 were found to be 75%, 86%, 50%, and 95%,
      respectively. DISCUSSION: Retrospective evaluation of geriatric patients with
      acute appendicitis, according to the total number of their comorbidities,
      surprisingly revealed no statistical difference between groups. We thought that a
      high Mannheim peritonitis index score is a more reliable criteria than the total
      number of comorbidities in predicting the prognosis of patients with acute
      appendicitis in the geriatric population.

PMID- 20134383
TI  - Intraoperative fetal heart rate monitoring during nonobstetric surgery in
      pregnancy: a practice survey.
AB  - OBJECTIVE: To assess practice patterns concerning intraoperative fetal heart rate
      monitoring during nonobstetric surgery in pregnancy among members of the
      Association of Professors of Gynecology and Obstetrics (APGO). STUDY DESIGN: A 16
      question survey regarding intraoperative fetal heart rate monitoring during
      nonobstetric surgery was delivered to the 1300 APGO members via email.
      Descriptive statistics were used to determine the reasons for fetal monitoring
      during nonobstetric surgery in pregnancy. RESULTS: Concerning intraoperative
      monitoring during nonobstetric surgery, 98% of respondents recorded the fetal
      heart rate pre-and post-surgery, and 43% of respondents reported they usually
      monitor intraoperatively. Of the 1151 physicians surveyed, 16% completed the
      survey. CONCLUSION: The majority of APGO members surveyed do not employ
      intraoperative fetal heart rate monitoring during nonobstetric surgery in
      pregnancy.

PMID- 20134384
TI  - Divinum est opus sedare dolorem: pretending the divine in postoperative pain
      management.

PMID- 20134385
TI  - Antineoplastic agent-associated serpentine supravenous hyperpigmentation:
      superficial venous system hyperpigmentation following intravenous chemotherapy.
AB  - PURPOSE: To review the clinical characteristics and associated antineoplastic
      agents in patients who developed hyperpigmentation of the superficial venous
      system after chemotherapy. BACKGROUND: Serpentine supravenous hyperpigmentation
      was the term coined by Hrushesky to describe increased pigmentation of the skin
      immediately overlying the venous network used for intravenous infusion of 5
      fluorouracil. Subsequently this phenomenon has been observed in individuals
      treated with other chemotherapeutic agents. METHODS: A 45-year-old woman with
      breast cancer who developed serpentine supravenous hyperpigmentation after
      intravenous 5-fluorouracil is described. Published reports of other individuals
      who developed antineoplastic agent-associated serpentine supravenous
      hyperpigmentation are reviewed. RESULTS: Serpentine supravenous hyperpigmentation
      has most commonly been associated with 5-fluorouracil. Other chemotherapy drugs
      including alkylating agents, antibiotics, anti-microtubules, and proteasome
      inhibitors have also caused this distinctive pattern of pigmentation. Serpentine
      supravenous hyperpigmentation occurs predominately in men who are receiving
      treatment for solid tumors. CONCLUSIONS: Serpentine supravenous hyperpigmentation
      is an uncommon sequelae of antineoplastic therapy. Treatment with the associated
      drug may be continued since this adverse reaction to the chemotherapeutic agent
      is benign and self-limiting. The hyperpigmented streaks gradually resolve
      spontaneously after the medication has been stopped.

PMID- 20134386
TI  - Acute in-stent coronary thrombosis without ST change on electrocardiography: a
      case report and literature review.
AB  - Coronary stent thrombosis is a major complication which occurs in 0.5-1.9% of
      patients undergoing stent implantation. The case of a 65-year-old male who was
      admitted to the hospital due to chest pain is presented. A 12-lead
      electrocardiography showed complete AV block, acute inferior wall, and right
      ventricle myocardial infarction. Coronary angiography showed total occlusion of
      the right coronary artery. Successful stent implantation was performed with
      optimal angiographic result. However, the patient developed chest discomfort and
      12-lead electrocardiography showed no ST change. Coronary angiography revealed
      acute in-stent thrombosis. Another stent implantation was done with optimal
      angiographic result. Although rarely reported, acute in-stent thrombosis can be
      life-threatening, especially in cases where there is no ST change. For this
      reason, careful history taking and prompt coronary angiography may be life
      saving.

PMID- 20134387
TI  - Large pedunculated eccrine hidrocystoma: a case report.
AB  - Eccrine hidrocystomas are benign, small, cystic growths that characteristically
      occur on the eyelids, but away from the lid margin. The size of these growths are
      generally reported as being between 1 and 5 mm. The case of a patient with a very
      large hidrocystoma of the eyelid with a previously undescribed pedunculated
      morphology is presented. The pathologic features of this entity and the different
      diagnosis of cystic lesions are also discussed.

PMID- 20134388
TI  - Bilateral carotid stenting after a motor vehicle crash.
AB  - Extracranial carotid artery dissection after blunt trauma may manifest as
      arterial stenosis or occlusion or as dissecting aneurysm formation.
      Anticoagulation and/or antiplatelet therapy is the first-line treatment, but,
      because it is effective and less invasive than other procedures, endovascular
      treatment of carotid artery dissection has recently attracted interest. A small
      subset of patients with blunt carotid dissection, or pseudoaneurysms, have
      bilateral injuries which may be high risk for occlusion and ischemic stroke.
      Early carotid stenting and subsequent antiplatelet therapy may be an option in
      this patient group.

PMID- 20134389
TI  - Squamous cell carcinoma in an African American with discoid lupus erythematosus:
      a case report and review of the literature.
AB  - Discoid lupus is an autoimmune disorder with primarily cutaneous manifestations.
      Carcinomatous changes in discoid lupus can lead to the development of squamous
      cell carcinoma. While this most often occurs in Caucasians, the presented patient
      is an African American. She developed numerous squamous cell carcinomas in areas
      of scarring from discoid lupus. This case illustrates the need for careful
      observation of discoid lupus for the development of squamous cell carcinoma in
      the African American patient.

PMID- 20134390
TI  - Candida glabrata liver abscess and fungemia complicating severe calculus
      cholecystitis in an immunocompetent nondiabetic host.
AB  - We report a rare case of Candida glabrata liver abscess and fungemia complicating
      severe calculus cholecystitis in a 64-year-old female patient who had no history
      of immunosuppression or diabetes mellitus. The patient underwent cholecystectomy,
      resection of liver abscess, and systemic antifungal therapy using micafungin.

PMID- 20134391
TI  - Multiple myeloma presenting as recurrent sinopulmonary infections.
AB  - Multiple myeloma is a plasma cell malignancy that classically presents with bone
      pain secondary to osteolytic lesions, anemia, and renal insufficiency. A 49-year
      old man presented for workup of possible primary immunodeficiency due to a
      history of recurrent sinopulmonary infection and abnormal immunoglobulin levels.
      He was subsequently diagnosed with multiple myeloma, despite a lack of typical
      symptoms. The correct diagnosis of multiple myeloma can be easily overlooked,
      especially in a patient with recurrent infections but no other signs or symptoms
      typical of myeloma.

PMID- 20134392
TI  - Acute stent thrombosis: rare but still there.

PMID- 20134393
TI  - Endoscopic removal of a brunneroma with EUS guidance.
AB  - Brunner glands are compound tubular submucosal glands typically found in the
      duodenal bulb. The most common benign tumors of the small intestine are adenoma,
      and 25% of these occur in the duodenum. Among the benign tumors of the duodenum,
      30-50% arise from the Brunner glands. Most of the literature describes their
      presentations as ranging from benign, nonspecific, epigastric discomfort to
      obstruction and intestinal bleeding. A good percentage of them are surgically
      resected; however, there has been an advancement to remove them endoscopically.
      We present one of the first cases of an endoscopic ultrasound (EUS) approach to
      the diagnosis and therapeutic removal of a brunneroma.

PMID- 20134394
TI  - Interleukin-15 receptor blockade in non-human primate kidney transplantation.
AB  - BACKGROUND: Interleukin (IL)-15 is a chemotactic factor to T cells. It induces
      proliferation and promotes survival of activated T cells. IL-15 receptor blockade
      in mouse cardiac and islet allotransplant models has led to long-term engraftment
      and a regulatory T-cell environment. This study investigated the efficacy of IL
      15 receptor blockade using Mut-IL-15/Fc in an outbred non-human primate model of
      renal allotransplantation. METHODS: Male cynomolgus macaque donor-recipient pairs
      were selected based on ABO typing, major histocompatibility complex class I
      typing, and carboxy-fluorescein diacetate succinimidyl ester-based mixed
      lymphocyte responses. Once animals were assigned to one of six treatment groups,
      they underwent renal transplantation and bilateral native nephrectomy. Serum
      creatinine level was monitored twice weekly and as indicated, and protocol
      biopsies were performed. Rejection was defined as a increase in serum creatinine
      to 1.5 mg/dL or higher and was confirmed histologically. Complete blood counts
      and flow cytometric analyses were performed periodically posttransplant;
      pharmacokinetic parameters of Mut-IL-15/Fc were assessed. RESULTS: Compared with
      control animals, Mut-IL-15/Fc-treated animals did not demonstrate increased graft
      survival despite adequate serum levels of Mut-IL-15/Fc. Flow cytometric analysis
      of white blood cell subgroups demonstrated a decrease in CD8 T-cell and natural
      killer cell numbers, although this did not reach statistical significance.
      Interestingly, two animals receiving Mut-IL-15/Fc developed infectious
      complications, but no infection was seen in control animals. Renal pathology
      varied widely. CONCLUSIONS: Peritransplant IL-15 receptor blockade does not
      prolong allograft survival in non-human primate renal transplantation; however,
      it reduces the number of CD8 T cells and natural killer cells in the peripheral
      blood.

PMID- 20134395
TI  - Two-dimensional difference gel electrophoresis urinary proteomic profile in the
      search of nonimmune chronic allograft dysfunction biomarkers.
AB  - INTRODUCTION: Despite advances in therapeutics, graft loss associated with
      chronic allograft dysfunction (CAD) remains high. Urinary proteomic analysis is a
      noninvasive method that could be used to detect and evaluate CAD in renal
      transplant recipients. This study was aimed to establish the normal proteome map
      of stable transplant patients and to validate the utility of two-dimensional
      difference gel electrophoresis (2DE-DIGE) in identifying new candidates as
      urinary biomarkers of CAD. METHODS: Morning spot urine samples that were
      collected from kidney transplant recipients with biopsy-proven interstitial
      fibrosis and tubular atrophy (IFTA) stages 0-I-II/III (n=8/group) under
      immunosuppressive treatment with tacrolimus plus mycophenolate with or without
      prednisone. 2DE silver staining and mass spectrometry analyses were used to
      establish the normal proteome map, and 2DE-DIGE and mass spectrometry were used
      to identify proteins exhibiting differential abundance. RESULTS AND CONCLUSIONS:
      This study defines the normal proteome of stable renal transplant patients, which
      is composed of several plasma proteins, as well as of immunologic proteins that
      are probably specific to transplant recipients. The 2DE-DIGE study showed 19
      proteins with differential concentrations, depending on the IFTA histologic
      score. These 19 proteins could be used as urinary biomarkers of the severity of
      IFTA in renal transplant recipients.

PMID- 20134396
TI  - Heterogeneous inflammatory changes in liver graft recipients with normal
      biochemistry.
AB  - BACKGROUND: Patients with established liver grafts may receive excessive immune
      suppression. Liver biopsies were analyzed in those with normal liver biochemistry
      to identify parameters that might identify such cases. METHODS: Patients with
      established grafts (>3 years from engraftment) and normal liver biochemistry
      (normal alanine transaminase, alkaline phosphatase, and bilirubin) were invited
      to undergo liver biopsy. Liver tissue was assessed by routine histopathology, a
      modified Ishak score, and immunohistochemistry for lymphocyte and cell-cycle
      markers. Circulating and intrahepatic lymphocytes were subjected to flow
      cytometry. Data were subjected to principal component analysis. RESULTS: Two
      hundred twenty-five (40%) patients under regular review had an established graft
      with normal liver biochemistry; liver tissue was obtained in 55. Liver histology
      was normal in eight cases (14.5%). The most common abnormalities were mild
      nonspecific hepatitis in 25 (45.4%) and disease recurrence in 14 (25.4%).
      Principal component analysis identified a cluster of variables that accounted for
      a significant degree of variation within the dataset. These were lobular
      inflammation, portal inflammation, interface hepatitis, and fibrosis.
      CONCLUSIONS: Inflammation persisted in established grafted livers in most
      patients with normal liver biochemistry. Systematic histological and lymphocyte
      phenotype analysis generated an index that distinguished patient groups. Those
      with least inflammation and the lowest alanine transaminase may have a reduced
      requirement for immune suppression.

PMID- 20134397
TI  - NOD-scid IL2rgamma(null) mouse model of human skin transplantation and allograft
      rejection.
AB  - BACKGROUND: Transplantation of human skin on immunodeficient mice that support
      engraftment with functional human immune systems would be an invaluable tool for
      investigating mechanisms involved in wound healing and transplantation. Nonobese
      diabetic (NOD)-scid interleukin-2 gamma chain receptor (NSG) readily engraft with
      human immune systems, but human skin graft integrity is poor. In contrast, human
      skin graft integrity is excellent on CB17-scid bg (SCID.bg) mice, but they
      engraft poorly with human immune systems. METHODS: Human skin grafts transplanted
      onto immunodeficient NSG, SCID.bg, and other immunodeficient strains were
      evaluated for graft integrity, preservation of graft endothelium, and their
      ability to be rejected after engraftment of allogeneic peripheral blood
      mononuclear cells. RESULTS: Human skin transplanted onto NSG mice develops an
      inflammatory infiltrate, consisting predominately of host Gr1(+) cells, that is
      detrimental to the survival of human endothelium in the graft. Treatment of graft
      recipients with anti-Gr1 antibody reduces this cellular infiltrate, preserves
      graft endothelium, and promotes wound healing, tissue development, and graft
      remodeling. Excellent graft integrity of the transplanted skin includes
      multilayered stratified human epidermis, well-developed human vasculature, human
      fibroblasts, and passenger leukocytes. Injection of unfractionated, CD4 or CD8
      allogeneic human peripheral blood mononuclear cell induces a rapid destruction of
      the transplanted skin graft. CONCLUSIONS: NSG mice treated with anti-Gr1 antibody
      provide a model optimized for both human skin graft integrity and engraftment of
      a functional human immune system. This model provides the opportunity to
      investigate mechanisms orchestrating inflammation, wound healing,
      revascularization, tissue remodeling, and allograft rejection and can provide
      guidance for improving outcomes after clinical transplantation.

PMID- 20134398
TI  - Racial/ethnic disparities among children with diagnoses of perinatal HIV
      infection - 34 states, 2004-2007.
AB  - Early in the epidemic of human immunodeficiency virus/acquired immunodeficiency
      syndrome (HIV/AIDS) in the United States, racial/ethnic disparities were observed
      in the diagnoses of AIDS among adults and children. Since the early 1990s, the
      annual number of diagnoses of perinatally acquired AIDS and HIV infection has
      declined by approximately 90% in the United States as a result of routine HIV
      screening of pregnant women and the availability of effective interventions to
      prevent transmission. To characterize the most recent trends in diagnoses of
      perinatal HIV infection by race/ethnicity, CDC analyzed national HIV surveillance
      data for the period 2004-2007 from 34 states. This report summarizes the results
      of those analyses, which indicated that, during 2004-2007, 85% of diagnoses of
      perinatal HIV infection were in blacks or African Americans (69%) or Hispanics or
      Latinos (16%). The average annual rate of diagnoses of perinatal HIV infection
      during 2004-2007 was 12.3 per 100,000 among blacks, 2.1 per 100,000 among
      Hispanics, and 0.5 per 100,000 among whites. However, from 2004 to 2007, the
      racial/ethnic disparity narrowed, as the annual rate of diagnoses of perinatal
      HIV infection for black children decreased from 14.8 to 10.2 per 100,000, and the
      rate for Hispanic children decreased from 2.9 to 1.7 per 100,000. To further
      reduce perinatal HIV transmission and racial/ethnic disparities, HIV-infected
      pregnant women, and particularly black and Hispanic women, should receive timely
      prenatal care, early antiretroviral treatment, and other recommended
      interventions.

PMID- 20134399
TI  - Jimsonweed poisoning associated with a homemade stew - Maryland, 2008.
AB  - In the early morning hours of July 9, 2008, six adult family members were
      admitted to a hospital emergency department in Maryland with hallucinations,
      confusion, mydriasis, and tachycardia of approximately 3-4 hours duration.
      Approximately 4-5 hours earlier, all six family members had shared a meal of
      homemade stew and bread. Subsequent investigation by the Montgomery County
      Department of Health and Human Services (MCDHHS) and the Maryland Department of
      Health and Mental Hygiene (MDHMH) determined that the stew contained jimsonweed
      (Datura stramonium), a plant in the nightshade family that contains atropine and
      scopolamine and has been associated with anticholinergic-type poisoning. This
      report describes the poisoning incident, which resulted in six hospitalizations,
      and the subsequent multidisciplinary investigation. Health-care providers and
      public health officials should be aware that jimsonweed poisoning can occur among
      many age groups, including younger persons, who typically consume the plant
      material for recreational purposes, or persons of any age group who might
      unknowingly ingest the plant. A prompt diagnosis of jimsonweed poisoning is
      complicated by the difficulties in eliciting exposure histories in persons with
      altered mental status and the variable presentations of affected persons.
      Consultation with horticulturalists, poison control centers, and specialized
      laboratories might be necessary to investigate cases and outbreaks.

PMID- 20134400
TI  - State preemption of local smoke-free laws in government work sites, private work
      sites, and restaurants - United States, 2005-2009.
AB  - Smoke-free policies (i.e., policies that completely eliminate smoking in indoor
      workplaces and public places) result in health benefits, including preventing
      heart attacks. Preemptive legislation at the state level prohibits localities
      from enacting laws that vary from state law or are more stringent. A Healthy
      People 2010 objective (27-19) is to eliminate state laws that preempt stronger
      local tobacco control laws. A 2005 CDC review found that little progress was
      being made toward reducing the number of state laws preempting local smoking
      restrictions in three indoor settings: government work sites, private-sector work
      sites, and restaurants. These three settings were selected for analysis because
      they are settings that often are addressed by state and local smoking
      restrictions and because they are major settings where nonsmoking workers and
      patrons are exposed to secondhand smoke. This report updates the previous
      analysis and summarizes changes that occurred from December 31, 2004, to December
      31, 2009, in state laws that preempt local smoke-free laws for the same three
      settings. During that period, the number of states preempting local smoking
      restrictions in at least one of these three settings decreased from 19 to 12. In
      contrast with the 2005 findings, this decrease indicates progress toward
      achieving the goal of eliminating state laws preempting local smoking
      restrictions. Further progress could result in additional reductions in
      secondhand smoke exposure.

PMID- 20134401
TI  - Surveillance of certain health behaviors and conditions among states and selected
      local areas - Behavioral Risk Factor Surveillance System, United States, 2007.
AB  - PROBLEM: Chronic diseases (e.g., heart disease, cancer, stroke, and diabetes) are
      the leading causes of death in the United States. Controlling health risk
      behaviors (e.g., smoking, physical inactivity, poor diet, and excessive drinking)
      and using preventive health-care services (e.g., cancer, hypertension, and
      cholesterol screenings) can reduce morbidity and mortality from chronic diseases.
      Monitoring health-risk behaviors, chronic health conditions, and preventive care
      practices is essential to develop health promotion activities, intervention
      programs, and health policies at the state, city, and county levels. REPORTING
      PERIOD COVERED: January 2007-December 2007. DESCRIPTION OF THE SYSTEM: The
      Behavioral Risk Factor Surveillance System (BRFSS) is a state-based, on-going,
      random--digit-dialed household telephone survey of noninstitutionalized adults
      aged >or=18 years residing in the United States. BRFSS collects data on health
      risk behaviors and use of preventative health services related to the leading
      causes of death and disability in the United States. This report presents results
      for 2007 for all 50 states, the District of Columbia, the Commonwealth of Puerto
      Rico, Guam, the Virgin Islands, 184 metropolitan and micropolitan statistical
      areas (MMSAs), and 298 counties. RESULTS: In 2007, prevalence estimates of risk
      behaviors, chronic conditions, and the use of preventive services varied
      substantially by state and territory, MMSA, and county. The following is a
      summary of results listed by BRFSS question topic. Each set of proportions refers
      to the range of estimated prevalence for the disease, condition, or behavior, as
      reported by the survey subject. Adults who reported fair or poor health: 11% to
      32% for states and territories and 6% to 31% for MMSAs and counties. Adults with
      health-care coverage: 71% to 94% for states and territories and 51% to 97% for
      MMSAs and counties. Annual influenza vaccination among adults aged >or=65 years:
      32% to 80% for states and territories, 48% to 83% for MMSAs, and 44% to 88% for
      counties. Pneumococcal vaccination among adults aged >/=65 years: 26% to 74% for
      states and territories, 44% to 83% for MMSAs, and 39% to 87% for counties. Adults
      who had their cholesterol checked within the preceding 5 years: 66% to 85% for
      states and territories and 58% to 90% for MMSAs and counties. Adults who consumed
      at least 5 servings of fruits and vegetables per day: 14% to 33% for states and
      territories, 16% to 34% for MMSAs and 14% to 37% for counties. Adults who
      reported no leisure-time physical activity: 17% to 44% for states and territories
      and 9% to 38% for MMSAs and counties. Adults who engaged in moderate or vigorous
      physical activity: 31% to 61% for states and territories and 36% to 67% for MMSAs
      and counties. Adults who engaged in only vigorous physical activity: 19% to 40%
      for states and territories and 15% to 45% for MMSAs and counties. Cigarette
      smoking among adults: 9% to 31% for states and territories, 7% to 34% for MMSAs,
      and 7% to 30% for counties. Binge drinking among adults: 3% to 8% for states and
      territories. Adults classified as overweight: 33% to 40% for states and
      territories and 26% to 47% for MMSAs and counties. Adults aged >or=20 years who
      were obese: 20% to 34% for states and territories and 14% to 38% for MMSAs and
      counties. Adults who were told of a diabetes diagnosis: 5% to 13% for states and
      territories and 2% to 17% for MMSAs and counties. Adults with high blood pressure
      diagnosis: 21% to 35% for states and territories and 16% to 38% for MMSAs and
      counties. Adults who had high blood cholesterol: 28% to 43% for states and
      territories, 29% to 49% for MMSAs, and 26% to 51% for counties. Adults with a
      history of coronary heart disease: 2% to 14% for states and territories, MMSAs,
      and counties. Adults who were told of a stroke diagnosis: 1% to 7% for states and
      territories, MMSAs, and counties. Adults who were diagnosed with arthritis: 14%
      to 36% for states and territories and 16% to 40% for MMSAs and counties. Adults
      who had asthma: 5% to 10% for states and territories and 3% to 13% for MMSAs and
      counties. Adults with activity limitation associated with physical, mental, or
      emotional problems: 10% to 26% for states and territories. Adults who required
      special equipment because of health problems: 3% to 10% for states and
      territories and 3% to 14% for MMSAs and counties. INTERPRETATION: The findings in
      this report indicate substantial variation in self-reported health status, health
      care coverage, use of preventive health-care services, health behaviors leading
      to chronic health conditions, and disability among U.S. adults at the state and
      territory, MMSA, and county levels. The findings underscore the continued need
      for surveillance of health-risk behaviors, chronic diseases and conditions, and
      the use of preventive services. PUBLIC HEALTH ACTIONS: Healthy People 2010 (HP
      2010) objectives have been established to monitor health behaviors and the use of
      preventive health services. Local and state health departments and federal
      agencies use BRFSS data to identify populations at high risk for certain health
      behaviors, chronic diseases and conditions and to evaluate the use of preventive
      services. In addition, BRFSS data are used to direct, implement, monitor, and
      evaluate public health programs and policies that can lead to a reduction in
      morbidity and mortality.

PMID- 20134402
TI  - Primary culture and plasmid electroporation of the murine organ of Corti.
AB  - In all mammals, the sensory epithelium for audition is located along the
      spiraling organ of Corti that resides within the conch shaped cochlea of the
      inner ear (fig 1). Hair cells in the developing cochlea, which are the
      mechanosensory cells of the auditory system, are aligned in one row of inner hair
      cells and three (in the base and mid-turns) to four (in the apical turn) rows of
      outer hair cells that span the length of the organ of Corti. Hair cells transduce
      sound-induced mechanical vibrations of the basilar membrane into neural impulses
      that the brain can interpret. Most cases of sensorineural hearing loss are caused
      by death or dysfunction of cochlear hair cells. An increasingly essential tool in
      auditory research is the isolation and in vitro culture of the organ explant.
      Once isolated, the explants may be utilized in several ways to provide
      information regarding normative, anomalous, or therapeutic physiology. Gene
      expression, stereocilia motility, cell and molecular biology, as well as
      biological approaches for hair cell regeneration are examples of experimental
      applications of organ of Corti explants. This protocol describes a method for the
      isolation and culture of the organ of Corti from neonatal mice. The accompanying
      video includes stepwise directions for the isolation of the temporal bone from
      mouse pups, and subsequent isolation of the cochlea, spiral ligament, and organ
      of Corti. Once isolated, the sensory epithelium can be plated and cultured in
      vitro in its entirety, or as a further dissected micro-isolate that lacks the
      spiral limbus and spiral ganglion neurons. Using this method, primary explants
      can be maintained for 7-10 days. As an example of the utility of this procedure,
      organ of Corti explants will be electroporated with an exogenous DsRed reporter
      gene. This method provides an improvement over other published methods because it
      provides reproducible, unambiguous, and stepwise directions for the isolation,
      microdissection, and primary culture of the organ of Corti.

PMID- 20134403
TI  - ESCRT-II coordinates the assembly of ESCRT-III filaments for cargo sorting and
      multivesicular body vesicle formation.
AB  - The sequential action of five distinct endosomal-sorting complex required for
      transport (ESCRT) complexes is required for the lysosomal downregulation of cell
      surface receptors through the multivesicular body (MVB) pathway. On endosomes,
      the assembly of ESCRT-III is a highly ordered process. We show that the length of
      ESCRT-III (Snf7) oligomers controls the size of MVB vesicles and addresses how
      ESCRT-II regulates ESCRT-III assembly. The first step of ESCRT-III assembly is
      mediated by Vps20, which nucleates Snf7/Vps32 oligomerization, and serves as the
      link to ESCRT-II. The ESCRT-II subunit Vps25 induces an essential conformational
      switch that converts inactive monomeric Vps20 into the active nucleator for Snf7
      oligomerization. Each ESCRT-II complex contains two Vps25 molecules (arms) that
      generate a characteristic Y-shaped structure. Mutant 'one-armed' ESCRT-II
      complexes with a single Vps25 arm are sufficient to nucleate Snf7
      oligomerization. However, these oligomers cannot execute ESCRT-III function. Both
      Vps25 arms provide essential geometry for the assembly of a functional ESCRT-III
      complex. We propose that ESCRT-II serves as a scaffold that nucleates the
      assembly of two Snf7 oligomers, which together are required for cargo
      sequestration and vesicle formation during MVB sorting.

PMID- 20134404
TI  - Differences in emotion processing in patients with essential and secondary
      hypertension.
AB  - BACKGROUND: An impaired ability to experience and express emotions, known as
      alexithymia, has previously been associated with hypertension. Alexithymia and
      related emotion-processing variables, however, have never been examined as a
      function of the type of hypertension, essential (EH) or secondary (SH). METHODS:
      Our working hypothesis was that if dysregulated emotional processes play a key
      neurobiological role in EH, they would be less present in hypertension due to
      specific medical causes or SH. A total of 98 consecutive hypertensive patients
      (73 EH, 25 SH) with similar blood pressure levels completed two complementary
      measures of emotion processing: the 20-item Toronto Alexithymia Scale (TAS-20)
      and the Levels of Emotional Awareness Scale (LEAS). RESULTS: After controlling
      for confounding variables, LEAS score was lower in EH than SH (estimated means:
      46.4 vs. 52.0; P = 0.028; effect size 0.52). TAS-20 scores did not differentiate
      EH from SH, but the differences were in the expected direction, with an effect
      size of 0.34 for TAS-20 total score. Neither psychometric measure was associated
      with the duration of hypertension or the presence of cardiovascular (CV)
      complications. CONCLUSIONS: These results are consistent with a contribution of
      an emotional or psychosomatic component in EH and may have practical implications
      for the nonpharmacological management of hypertension. They also demonstrate the
      utility of complementary measures of emotion processing in medically ill
      patients.

PMID- 20134405
TI  - Effects of Korean red ginseng (Panax ginseng C.A. Mayer) and its isolated
      ginsenosides and polysaccharides on arterial stiffness in healthy individuals.
AB  - BACKGROUND: Preclinical studies indicate a role of Korean red ginseng (KRG) in
      the modulation of vascular function; however, clinical evidence is scarce.
      Therefore, the objective of this study was to investigate the effect of KRG root
      on peripheral blood pressure (BP) and augmentation index (AI), an emerging method
      to assess cardiovascular risk beyond conventional BP measurements. Furthermore,
      in an attempt to elucidate which of the major components of KRG is responsible
      for these effects, the ginsenoside and polysaccharide fractions isolated from the
      same KRG root were also investigated. METHODS: The study was designed as an acute
      randomized, controlled, double blind, crossover trial. A total of 17 healthy
      fasted individuals (gender: 9 males:8 females, age: 30 +/- 9 years, body mass
      index: 25 +/- 3 kg/m(2), systolic BP (SBP): 110 +/- 10.1, diastolic BP (DBP): 65
      +/- 7 mm Hg) received, on separate occasions, four treatments consisting of: 3 g
      of either placebo, KRG root, or a KRG root bioequivalent dose of ginsenoside or
      polysaccharide fractions. BP and AI were measured by applanation tonometry at
      baseline, 1, 2, and 3 h post-treatment. RESULTS: Compared to placebo, 3 g of KRG
      significantly lowered radial AI by 4.6% (P = 0.045), whereas the ginsenoside
      fraction comparably decreased AI by 4.8% (P = 0.057), and no effect was observed
      with the polysaccharides. There were no differences in BP between treatments.
      CONCLUSION: Although preliminary, this study is the first to demonstrate that KRG
      may improve arterial stiffness as measured by AI. In addition, it appears that
      ginsenosides may be the principal pharmacologically active component of the root,
      rather than the polysaccharide fraction. This study supports the results seen
      with KRG in the preclinical studies and warrants further investigation on acute
      and long-term endothelial parameters.

PMID- 20134406
TI  - Associations between collagen synthesis and degradation and aortic function in
      arterial hypertension.
AB  - BACKGROUND: Studies have suggested that collagen accumulation in the aortic wall
      may contribute to the stiff aorta in arterial hypertension. However, data in
      human hypertension are limited. In this investigation, relations between markers
      of collagen metabolism and aortic function in patients with arterial hypertension
      were evaluated. METHODS: We studied 72 hypertensive patients (age 53 +/- 5 years)
      and 27 age- and gender-matched normotensive individuals. Elastic properties of
      the aorta were assessed by aortic pulse wave velocity (carotid-to-femoral pulse
      wave velocity (PWVc-f)). Free amino-terminal propeptides of precollagen type I
      (PINP, reflecting collagen I synthesis), serum telopeptides of collagen type I
      (CITP, an index of collagen I degradation), free amino-terminal propeptides on
      precollagen type III (PIIINP, reflecting collagen III metabolism),
      prometalloproteinase-1 (proMMP-1), and tissue inhibitor of metalloproteinase-1
      (TIMP-1) levels were determined by commercially available immunoassays. RESULTS:
      Patients with arterial hypertension had greater PWVc-f (P = 0.01); and higher
      levels of PINP/CITP compared to control (P = 0.04). PWVc-f was significantly
      associated with PINP/CITP ratio (analysis of variance (ANOVA), P = 0.03).
      Hypertensive patients had significantly higher levels of proMMP-1/TIMP-1 (P =
      0.04); PWVc-f was significantly associated with proMMP-1 (ANOVA, P = 0.03) and
      proMMP-1/TIMP-1 (ANOVA, P = 0.04). Associations between PWVc-f and proMMP-1 and
      between PWVc-f and PINP/CITP ratio remained significant after adjustment for PWVc
      f confounders and antihypertensive treatment. CONCLUSIONS: Alterations in
      collagen turnover that favor collagen type I synthesis; as well as proMMP-1
      expression are related to increased aortic stiffness in treated hypertensive
      individuals without left ventricular (LV) hypertrophy.

PMID- 20134407
TI  - A triglyceride-raising APOA5 genetic variant is negatively associated with
      obesity and BMI in the Chinese population.
AB  - Apolipoprotein A-V (apo A-V) exerts a potent triglyceride (TG)-lowering effect
      through enhanced intravascular TG-hydrolysis with increased uptake of TG-derived
      free fatty acids into muscle and adipose tissue. Genetic variants in the APOA5
      gene were strongly associated with plasma TG concentrations. The aim of this
      study was to examine whether APOA5 genetic variation was associated with obesity.
      We genotyped the missense c.553 G>T polymorphism (p.G185C) in the APOA5 gene in
      1,085 Chinese (333 obese subjects and 752 nonobese controls). We analyzed the
      association between the c.553 G>T polymorphism and obesity and related metabolic
      phenotypes. The T allele at the c.553 G>T polymorphism was associated with higher
      plasma TG concentrations. Each additional T allele was associated with an
      increased TG concentration of 53.5 mg/dl (95% confidence interval (CI) 29.6-76.0,
      P < 0.0001). However, the T allele was associated lower risk of obesity (odds
      ratio (OR), 0.48; 95% CI 0.32-0.73, P = 0.0004). Each additional copy of the T
      allele was associated with a BMI decrease of 0.73 kg/m(2) (95% CI 0.26-1.16, P =
      0.002), equivalent to 2.11 kg in a person 1.7 m tall. We may then conclude that
      the TG-raising APOA5 genetic variant was associated with a decrease in BMI and
      reduced risk of obesity in the Chinese population.

PMID- 20134408
TI  - Increased food intake and energy expenditure following administration of
      olanzapine to healthy men.
AB  - Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and
      increase the risk of diabetes in patients with schizophrenia. The goal of this
      study was to assess potential mechanisms of OLZ-induced weight gain and
      accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and
      placebo (PBO) in a randomized, double-blind, crossover study. In periods 1 and 2,
      subjects received OLZ (5 mg for 3 days then OLZ 10 mg for 12 days) or matching
      PBO separated by a minimum 12-day washout. Twenty-four hour food intake (FI),
      resting energy expenditure (REE), activity level, metabolic markers, and insulin
      sensitivity (IS) were assessed. In total, 30 subjects were enrolled and 21
      completed both periods. Mean age and BMI were 27 years (range: 18-49 years) and
      22.6 +/- 2.2 kg/m(2), respectively. Relative to PBO, OLZ resulted in a 2.62 vs.
      0.08 kg increase in body weight (P < 0.001) and 18% (P = 0.052 or 345 kcal)
      increase in FI. Excluding one subject with nausea and dizziness on the day of OLZ
      FI measurement, the increase in FI was 547 kcal, (P < 0.05). OLZ increased REE
      relative to PBO (113 kcal/day, P = 0.003). Significant increases in
      triglycerides, plasminogen activator inhibitor-I (PAI-I), leptin, and tumor
      necrosis factor-alpha (TNF-alpha) were observed. No significant differences in
      activity level or IS were observed. This study provides evidence that OLZ
      pharmacology drives the early increase in weight through increased FI, without
      evidence of decreased energy expenditure (EE), activity level, or short-term
      perturbations in IS.

PMID- 20134409
TI  - Independent associations between cardiorespiratory fitness and abdominal obesity
      with metabolic risk in adolescents and adults.
AB  - Our objective was to examine the independent association between abdominal
      obesity (waist circumference (WC)) and cardiorespiratory fitness (CRF) with
      metabolic syndrome (MetS) in 2,197 adults (ages 20-49 years) and 3,223
      adolescents (ages 12-19 years). Individuals were stratified by CRF and WC using
      sex- and age-specific MetS criteria for adolescents and adults. Adolescents had a
      lower prevalence rate of MetS (5.4% vs. 12.8%) and high WC (15.5% vs. 35.7%), but
      a higher prevalence rate of low CRF (37.6% vs. 15.9%) than adults. As compared to
      adolescents and adults with low WC, those with a high WC (odds ratio (OR) = 5.5
      16.5, P < 0.001) were more likely to have a clustering of MetS factors than those
      with low WC (OR = 1.2-3.8, P = 0.3 to <0.001), regardless of fitness level.
      Conversely, the beneficial effects of having moderate/high CRF on MetS were only
      observed in individuals with low WC, and not high WC. Thus, in conclusion, both
      high WC and low CRF are associated with increased odds of MetS in adolescents and
      adults. However, increased abdominal obesity is more strongly associated with
      MetS in adolescents and adults.

PMID- 20134410
TI  - Nutrient specific feeding and endocrine effects of jejunal infusions.
AB  - Intestinal nutrient infusions result in variable decreases in food intake and
      body weight based on the nutrient type and the specific intestinal infusion site.
      Only intrajejunal infusions of fatty acids decrease food intake beyond the
      calories infused. To test whether this extra-compensatory decrease in food intake
      is specific to fatty acids, small volume intrajejunal infusions of glucose (Glu)
      and casein hydrolysate (Cas), as well as linoleic acid (LA) were administered to
      male Sprague-Dawley rats. Equal kilocalorie (kcal) loads of these nutrients
      (11.4) or vehicle were infused into the jejunum over 7 h/day for five consecutive
      days. Food intake was continuously monitored and body weight was measured daily.
      After the infusion on the final day, rats were killed and plasma collected.
      Intrajejunal infusions of LA and Glu, but not Cas, suppressed food intake beyond
      the caloric load of the infusate with no compensatory increase in food intake
      after the infusion period. Rats receiving LA and Glu infusions also lost
      significant body weight across the infusion days. Plasma glucagon-like peptide-1
      (GLP-1) was increased in both the LA and Glu rats compared with control animals,
      with no significant change in the Cas-infused animals. Peptide YY (PYY) levels
      increased in response to LA and Cas infusions. These results suggest that
      intrajejunal infusions of LA and Glu may decrease food intake and body weight via
      alterations in GLP-1 signaling. Thus, particular nutrients are more effective at
      producing decreases in food intake, body weight, and inducing changes in peptide
      levels and could lead to a novel therapy for obesity.

PMID- 20134411
TI  - Lack of association between PCK1 polymorphisms and obesity, physical activity,
      and fitness in European Youth Heart Study (EYHS).
AB  - Phosphoenolpyruvate carboxykinase-1 (PCK1) is the rate-limiting enzyme in the
      hepatic gluconeogenic pathway. Studies have shown that overexpression of Pck1 in
      mice results in obesity-related traits and higher levels of physical activity
      (PA). Therefore, our aims were to investigate whether common genetic variation in
      the PCK1 gene influences obesity-related traits, PA, and fitness, and to examine
      whether PA and fitness attenuate the influence of the PCK1 polymorphisms on
      obesity in children. Analyses were undertaken on data from Danish and Estonian
      children (958 boys and 1,104 girls) from the European Youth Heart Study (EYHS), a
      school-based, cross-sectional study of children (mean +/- s.d. age: 9.6 +/- 0.4
      years) and adolescents (15.5 +/- 0.5 years). We genotyped eight polymorphisms
      that captured the common genetic variations in the PCK1 gene. The association
      between the PCK1 polymorphisms and BMI, waist circumference (WC), sum of four
      skinfolds, PA, and fitness was tested using an additive model adjusted for age,
      age-group, gender, maturity, and country. Interactions were tested by including
      interaction terms in the model. None of the polymorphisms were significantly
      associated with BMI, WC, sum of four skinfolds, PA, and fitness, and also with
      the risk of being overweight or obese (P > 0.05). The interactions between the
      polymorphisms and age-group, gender, PA, and fitness were not statistically
      significant. This is the first study to comprehensively examine the association
      of PCK1 polymorphisms with obesity, PA, and fitness. Despite strong evidence from
      animal studies, our study in the EYHS cohort failed to identify an association of
      PCK1 polymorphisms with obesity, PA, and fitness.

PMID- 20134412
TI  - Physical activity energy expenditure of adolescents in India.
AB  - Physical activity (PA) has rarely been quantified in adolescent populations
      undergoing economic transition; therefore relationships with disease still remain
      uncertain. This study assessed whether absolute PA energy expenditure (PAEE),
      PAEE/kg, and PAEE/kg(FFM) could be accurately estimated using accelerometry and a
      questionnaire in Indian adolescents and how these values compared to those of
      other populations. PAEE was assessed using doubly labeled water (DLW) in 30
      adolescents from Chennai, India, over seven consecutive days, simultaneous with
      the measurement of PA using accelerometry and a previous-week recall
      questionnaire. Accelerometry counts (regression analysis) and questionnaire data
      were used to estimate PAEE; estimates were cross-validated using the Bland-Altman
      method. Accelerometry data and DLW-derived PAEE were visually compared to values
      from four North American and European populations. For boys, 49% of the variance
      in DLW-derived PAEE was explained with an equation including accelerometry counts
      and fat-free mass (FFM). Questionnaire-derived estimates did not contribute to
      the explained variance in DLW derived PAEE. The group-level PA of these Indian
      adolescents was successfully assessed using accelerometry, but not questionnaire.
      DLW-derived PAEE/kg(FFM) (mean (s.d.): 53.0 (27.5) kJ/kg(FFM)/day) was lower in
      this group than other adolescent populations in Europe and similar to those in
      North America. Additionally, four boys and none of the girls accumulated >=60
      min/day of accelerometry-derived moderate intensity activity, indicating low
      levels of PAEE and PA in these adolescents. Further research is necessary to
      investigate the association between PA and health outcomes in Indian adolescents.

PMID- 20134413
TI  - Clinical profile and management of patients with hypertension and chronic
      ischemic heart disease according to BMI.
AB  - Obesity is associated with numerous risk factors and comorbidities such as
      hypertension, metabolic syndrome, type 2 diabetes, and cardiovascular diseases.
      However, numerous studies have reported an obesity paradox; the overweight and
      obese patients with established cardiovascular disease have better prognosis than
      those with a BMI <25 kg/m(2). This study was designed to assess potential
      differences in the clinical profile and management of hypertensive outpatients
      with chronic ischemic heart disease in obese and lean patients that could explain
      these two apparently contradictory points. Overweight and obesity were defined as
      a BMI 25-29.9 kg/m(2) and >=30 kg/m(2), respectively. Cardiovascular risk factors
      goals were considered according to European Society of Hypertension-European
      Society of Cardiology 2003, National Cholesterol Education Program Adult
      Treatment Panel III and American Diabetes Association 2005 guidelines. A sample
      of 2,024 patients (66.8 +/- 10.1 years; 31.7% women) was included. Of these, 0.1%
      had a BMI <20 kg/m(2); 17.1% BMI 20-24.9 kg/m(2); 53.7% BMI 25-29.9 kg/m(2);
      23.7% BMI 30-34.9 kg/m(2); 4.3% BMI 35-39.9 kg/m(2); and 1.1% BMI >=40 kg/m(2).
      The subgroup of patients with BMI >=30 kg/m(2) had a higher proportion of women,
      diastolic dysfunction, diabetes, dyslipidemia, left ventricular hypertrophy, and
      heart failure. There was an inverse relationship between risk factors control
      rates and BMI (all comparisons BMI 20-24.9 kg/m(2) vs. 25-29.9 kg/m(2) vs. >=30
      kg/m(2)): blood pressure (BP) control (51.7% vs. 42.4% vs. 29.2%, P < 0.001); low
      density lipoprotein cholesterol (LDL-C) control (35.2% vs. 30.5% vs. 27.9%, P =
      0.03) and diabetes control (38.6% vs. 27.6% vs. 22.2%, P = 0.023). In conclusion,
      in patients with hypertension and chronic ischemic heart disease, as BMI
      increases, the clinical profile worsens as well as risk factors control rates.

PMID- 20134414
TI  - High plasma phospholipase A2 activity, inflammation markers, and LDL alterations
      in obesity with or without type 2 diabetes.
AB  - Plasma phospholipases A(2) (PLA(2)) hydrolyze phospholipids of circulating
      lipoproteins or deposited in arteries producing bioactive lipids believed to
      contribute to the atherosclerotic inflammatory response. PLA(2)(s) are elevated
      in obesity and type 2 diabetes (T2D) but it is not clear which of these
      conditions is the cause since they frequently coexist. This study attempts to
      evaluate if high plasma PLA(2)(s) activities and markers of their effects in
      lipoproteins are associated with obesity or T2D diabetes, or with both. Total
      PLA(2) and Ca(2+)-dependent and -independent activities, lipids, lipoproteins,
      apoAI, and apoB apolipoproteins and affinity of apoB-lipoproteins for arterial
      proteoglycans were measured, as well as Inflammation markers. These parameters
      were evaluated in plasma samples of four groups: (i) apparently healthy controls
      with normal BMI (nBMI), (ii) obese subjects with no T2D, (iii) patients with T2D
      but with nBMI, and (iv) obese patients with T2D. PLA(2) activities were measured
      in the presence and absence of Ca(2+) and in the presence of specific inhibitors.
      Obese subjects, with or without T2D, had high activities of total PLA(2) and of
      Ca(2+)-dependent and Ca(2+)-independent enzymes. The activities were correlated
      with inflammation markers in obese subjects with and without diabetes and with
      alterations of low-density lipoproteins (LDLs) that increased their affinity for
      arterial proteoglycans. Ca(2+)-dependent secretory (sPLA(2)) enzymes were the
      main responsible of the obesity-associated high activity. We speculate that
      augmented PLA(2)(s) activity that increases affinity of circulating LDL for
      arterial intima proteoglycans could be another atherogenic component of obesity.

PMID- 20134415
TI  - Adipocytes IGFBP-2 expression in prepubertal obese children.
AB  - Aims of the study were to measure insulin-like growth factor-binding protein-2
      (IGFBP-2) expression by abdominal subcutaneous adipocytes and to assess the
      relationship between IGFBP-2 expression, circulating IGFBP-2, obesity, and
      insulin sensitivity in obese children. Thirty-eight obese children were
      recruited. Insulin sensitivity was assessed by intravenous glucose tolerance test
      and body composition by total-body dual-energy X-ray absorptiometry. Serum free
      and total IGF-I, IGFBP-2, adiponectin, and leptin were measured. Relative
      quantification of IGFBP-2 mRNA by subcutaneous adipose tissue biopsies was
      obtained using real-time PCR. Circulating IGFBP-2 was positively associated with
      insulin sensitivity, in agreement with previous studies. IGFBP-2 expression was
      associated with fat mass percentage (r = 0.656; P < 0.02), insulin sensitivity (r
      = -0.604; P < 0.05), free IGF-I (r = 0.646; P < 0.05), and leptin (r = 0.603; P <
      0.05), but not with circulating IGFBP-2 (r = 0.003, P = ns). The association
      between IGFBP-2 expression and adiposity (r = 0.648; P < 0.05) was independent of
      insulin sensitivity (covariate). In conclusion, circulating IGFBP-2 was
      positively associated with insulin sensitivity. IGFBP-2 was expressed by
      subcutaneous abdominal adipocytes of obese children and increased with adiposity,
      independently from the level of insulin sensitivity. IGFBP-2 expression may
      potentially be one of the local mechanisms used by adipocytes to limit further
      fat gain.

PMID- 20134416
TI  - Effects of adiposity and 30 days of caloric restriction upon protein metabolism
      in moderately vs. severely obese women.
AB  - Protein metabolism adapts during caloric restriction (CR) to minimize protein
      loss, and it is unclear whether greater fat stores favorably affect this
      response. We sought to determine whether protein metabolism is related to degree
      of obesity and whether the response to CR is impacted by pre-CR adiposity level.
      Whole body protein metabolism was studied in 12 obese women over a wide range of
      BMI (30-53 kg/m(2)) as inpatients using [1-(13)C]leucine as a tracer following 5
      days of a weight-maintaining diet and then after 30 days of CR (1,400 kcal
      deficit with maintained protein intake). When expressed as total rates, per body
      weight (BW) or per fat-free mass (FFM), leucine rate of appearance (Ra), and
      nonoxidative leucine disposal (NOLD) were significantly higher in the individuals
      with a greater degree of obesity (P < 0.05). Leucine oxidation (Rox) was also
      higher in more highly obese women when expressed as a total rate (P < 0.05) but
      not if expressed per BW or FFM. CR reduced BW, FFM, and fat mass (P < 0.001), and
      declines were relatively similar between individuals. CR reduced Ra (P < 0.001),
      NOLD (P < 0.01), and Rox (P < 0.05), and the relative decline was not affected by
      differences in fat mass. CR-induced declines were significant even when Ra and
      NOLD were normalized to BW or FFM. We conclude that fat mass, like FFM, is a key
      determinant of protein turnover. However, during CR, higher fat mass does not
      favorably alter the response of protein metabolism and does not mitigate the loss
      of FFM.

PMID- 20134417
TI  - Hypobaric hypoxia causes body weight reduction in obese subjects.
AB  - The reason for weight loss at high altitudes is largely unknown. To date, studies
      have been unable to differentiate between weight loss due to hypobaric hypoxia
      and that related to increased physical exercise. The aim of our study was to
      examine the effect of hypobaric hypoxia on body weight at high altitude in obese
      subjects. We investigated 20 male obese subjects (age 55.7 +/- 4.1 years, BMI
      33.7 +/- 1.0 kg/m(2)). Body weight, waist circumference, basal metabolic rate
      (BMR), nutrition protocols, and objective activity parameters as well as
      metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin
      were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at
      the end of a 1-week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after
      returning to LA (D42). Although daily pace counting remained stable at high
      altitude, at D14 and D42, participants weighed significantly less and had higher
      BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased
      significantly at high altitude despite the reduction in body weight. Diastolic
      blood pressure was significantly lower at D7, D14, and D42 compared to D1. This
      study shows that obese subjects lose weight at high altitudes. This may be due to
      a higher metabolic rate and reduced food intake. Interestingly, leptin levels
      rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to
      play a major role, although the physiological mechanisms remain unclear. Weight
      loss at high altitudes was associated with clinically relevant improvements in
      diastolic blood pressure.

PMID- 20134418
TI  - Bilateral multielectrode neurophysiological recordings coupled to local
      pharmacology in awake songbirds.
AB  - Here we describe a protocol for bilateral multielectrode neurophysiological
      recordings during intracerebral pharmacological manipulations in awake songbirds.
      This protocol encompasses fitting adult animals with head-posts and recording
      chambers, and acclimating them to periods of restraint. The adaptation period is
      followed by bilateral penetrations of multiple electrodes to obtain acute,
      sensory-driven neurophysiological responses before versus during the application
      of pharmacological agents of interest. These local manipulations are achieved by
      simultaneous and restricted drug infusions carried out independently for each
      hemisphere. We have used this protocol to elucidate how neurotransmitter and
      neuroendocrine systems shape the auditory and perceptual processing of natural,
      learned communication signals. However, this protocol can be used to explore the
      neurochemical basis of sensory processing in other small vertebrates.
      Representative results and troubleshooting of key steps of this protocol are
      presented. Following the animal's recovery from head-post and recording chamber
      implantation surgery, the length of the procedure is 2 d.

PMID- 20134419
TI  - Thinned-skull cranial window technique for long-term imaging of the cortex in
      live mice.
AB  - Imaging neurons, glia and vasculature in the living brain has become an important
      experimental tool for understanding how the brain works. Here we describe in
      detail a protocol for imaging cortical structures at high optical resolution
      through a thinned-skull cranial window in live mice using two-photon laser
      scanning microscopy (TPLSM). Surgery can be performed within 30-45 min and images
      can be acquired immediately thereafter. The procedure can be repeated multiple
      times allowing longitudinal imaging of the cortex over intervals ranging from
      days to years. Imaging through a thinned-skull cranial window avoids exposure of
      the meninges and the cortex, thus providing a minimally invasive approach for
      studying structural and functional changes of cells under normal and pathological
      conditions in the living brain.

PMID- 20134420
TI  - Scototaxis as anxiety-like behavior in fish.
AB  - The scototaxis (dark/light preference) protocol is a behavioral model for fish
      that is being validated to assess the antianxiety effects of pharmacological
      agents and the behavioral effects of toxic substances, and to investigate the
      (epi)genetic bases of anxiety-related behavior. Briefly, a fish is placed in a
      central compartment of a half-black, half-white tank; following habituation, the
      fish is allowed to explore the tank for 15 min; the number and duration of
      entries in each compartment (white or black) are recorded by the observer for the
      whole session. Zebrafish, goldfish, guppies and tilapias (all species that are
      important in behavioral neurosciences and neuroethology) have been shown to
      demonstrate a marked preference for the dark compartment. An increase in white
      compartment activity (duration and/or entries) should reflect antianxiety
      behavior, whereas an increase in dark compartment activity should reflect anxiety
      promoting behavior. When individual animals are exposed to the apparatus on only
      one occasion, results can be obtained in 20 min per fish.

PMID- 20134421
TI  - Practical cell-free protein synthesis system using purified wheat embryos.
AB  - Biochemical characterization of each gene product encoded in the genome is
      essential to understand how cells are regulated. The bottleneck has been and
      still is in how the gene products can be obtained. The wheat cell-free protein
      synthesis system we have developed is a powerful method for preparation of many
      different proteins at a time and also for preparation of large amounts of
      specific proteins for biochemical and structural analyses. Here, we show a method
      for preparation of the wheat embryo extract useful for the cell-free reactions,
      by which 5 ml of a high-activity extract is obtained in 4-5 d. We also describe
      the methods for small- and large-scale protein synthesis by hands-down operations
      with the use of mRNAs prepared by transcription of PCR products and pEU plasmids
      harboring the target cDNAs, which need 2-4 d excepting the time required for
      plasmid preparation.

PMID- 20134422
TI  - Isolation and cultivation of human keratinocytes from skin or plucked hair for
      the generation of induced pluripotent stem cells.
AB  - The ease of generating induced pluripotent stem (iPS) cells, and possibly their
      properties after reprogramming, depends on the origin of the somatic cell
      starting population. Reprogramming of keratinocytes is both faster and more
      efficient compared with fibroblasts, although more care is required when
      isolating, culturing and infecting these cells. In this study, we describe
      detailed protocols using both feeder-dependent and defined serum- and feeder-free
      conditions for culturing human keratinocytes from foreskin samples and punch
      biopsies, as well as how to isolate keratinocytes from plucked hair. We further
      describe culture techniques and approaches to efficiently infect and reprogram
      these cells for the purpose of generating iPS cells. The procedure of deriving
      keratinocytes takes 10-14 d, whereas reprogramming and the appearance of iPS cell
      colonies that can be isolated and established requires another 3-4 weeks.

PMID- 20134423
TI  - Regenerating cortical connections in a dish: the entorhino-hippocampal
      organotypic slice co-culture as tool for pharmacological screening of molecules
      promoting axon regeneration.
AB  - We present a method for using long-term organotypic slice co-cultures of the
      entorhino-hippocampal formation to analyze the axon-regenerative properties of a
      determined compound. The culture method is based on the membrane interphase
      method, which is easy to perform and is generally reproducible. The degree of
      axonal regeneration after treatment in lesioned cultures can be seen directly
      using green fluorescent protein (GFP) transgenic mice or by axon tracing and
      histological methods. Possible changes in cell morphology after pharmacological
      treatment can be determined easily by focal in vitro electroporation. The well
      preserved cytoarchitectonics in the co-culture facilitate the analysis of
      identified cells or regenerating axons. The protocol takes up to a month.

PMID- 20134424
TI  - Synchronous infection of SIV and HIV in vitro for virology, immunology and
      vaccine-related studies.
AB  - The development of an HIV vaccine will require a more precise understanding of
      the immunological and virological underpinnings of HIV infection. Magnetofection,
      the process of magnetizing HIV by coupling it to ferrous nanoparticles and
      coordinating infection using a magnetic field, synchronizes the viral replication
      cycle at attachment while recapitulating the events of natural infection.
      Although spinoculation also concentrates virus onto target cells to increase
      infection, it does not synchronize infection. The synchronization of HIV
      infection in vitro facilitates the study of events in the viral replication cycle
      and the antiviral immune response on timelines previously impossible.
      Furthermore, by infecting a high percentage of cells in a short time frame,
      magnetofection increases the throughput of in vitro assays. Once a virus stock is
      generated, magnetofection of target cells is rapid, requiring only 1-2 h. Here we
      present a detailed protocol for this assay and review its applications for
      studying the immune response to HIV.

PMID- 20134425
TI  - Targeted optogenetic stimulation and recording of neurons in vivo using cell-type
      specific expression of Channelrhodopsin-2.
AB  - A major long-term goal of systems neuroscience is to identify the different roles
      of neural subtypes in brain circuit function. The ability to causally manipulate
      selective cell types is critical to meeting this goal. This protocol describes
      techniques for optically stimulating specific populations of excitatory neurons
      and inhibitory interneurons in vivo in combination with electrophysiology. Cell
      type selectivity is obtained using Cre-dependent expression of the light
      activated channel Channelrhodopsin-2. We also describe approaches for minimizing
      optical interference with simultaneous extracellular and intracellular recording.
      These optogenetic techniques provide a spatially and temporally precise means of
      studying neural activity in the intact brain and allow a detailed examination of
      the effect of evoked activity on the surrounding local neural network. Injection
      of viral vectors requires 30-45 min, and in vivo electrophysiology with
      optogenetic stimulation requires 1-4 h.

PMID- 20134426
TI  - Defining transcribed regions using RNA-seq.
AB  - Next-generation sequencing technologies are revolutionizing genomics research. It
      is now possible to generate gigabase pairs of DNA sequence within a week without
      time-consuming cloning or massive infrastructure. This technology has recently
      been applied to the development of 'RNA-seq' techniques for sequencing cDNA from
      various organisms, with the goal of characterizing entire transcriptomes. These
      methods provide unprecedented resolution and depth of data, enabling simultaneous
      quantification of gene expression, discovery of novel transcripts and exons, and
      measurement of splicing efficiency. We present here a validated protocol for
      nonstrand-specific transcriptome sequencing via RNA-seq, describing the library
      preparation process and outlining the bioinformatic analysis procedure. While
      sample preparation and sequencing take a fairly short period of time (1-2 weeks),
      the downstream analysis is by far the most challenging and time-consuming aspect
      and can take weeks to months, depending on the experimental objectives.

PMID- 20134427
TI  - Nonlinear least-squares data fitting in Excel spreadsheets.
AB  - We describe an intuitive and rapid procedure for analyzing experimental data by
      nonlinear least-squares fitting (NLSF) in the most widely used spreadsheet
      program. Experimental data in x/y form and data calculated from a regression
      equation are inputted and plotted in a Microsoft Excel worksheet, and the sum of
      squared residuals is computed and minimized using the Solver add-in to obtain the
      set of parameter values that best describes the experimental data. The confidence
      of best-fit values is then visualized and assessed in a generally applicable and
      easily comprehensible way. Every user familiar with the most basic functions of
      Excel will be able to implement this protocol, without previous experience in
      data fitting or programming and without additional costs for specialist software.
      The application of this tool is exemplified using the well-known Michaelis-Menten
      equation characterizing simple enzyme kinetics. Only slight modifications are
      required to adapt the protocol to virtually any other kind of dataset or
      regression equation. The entire protocol takes approximately 1 h.

PMID- 20134428
TI  - In vitro screens for quorum sensing inhibitors and in vivo confirmation of their
      effect.
AB  - This article will introduce the reader to protocols intended for (i)
      identification of quorum sensing (QS) inhibitors (QSIs), (ii) characterization of
      these compounds in vitro and (iii) evaluation of these compounds in animal
      models. Traditional antimicrobial drugs are designed against planktonic bacteria
      and not against bacterial biofilms. In biofilms, bacteria are highly resistant to
      otherwise lethal treatments and they communicate with each other, thus enabling
      coordinated group behavior. For many years, we have focused on interference with
      cell to cell communication, also known as QS, with the aim of disabling the
      expression of virulence and reduction of antibiotic tolerance. Here we present
      protocols for screening and testing for acyl-homoserine lactone (AHL)-dependent
      QS inhibition. We also present protocols for the in vivo validation of QSIs as
      possible drug candidates. The presented methods allow the evaluation of QS
      inhibition by a potential drug candidate within 2-3 weeks.

PMID- 20134429
TI  - Preparation of the caspase-3/7 substrate Ac-DEVD-pNA by solution-phase peptide
      synthesis.
AB  - This protocol describes the gram-scale solution-phase synthesis of the
      colorimetric caspase-3/7 substrate Ac-DEVD-pNA. The caspase enzymes are integral
      to cellular inflammation and apoptotic cascades, and are commonly studied by cell
      biologists, medicinal chemists and chemical biologists. In particular, the
      assessment of caspase enzymatic activity is a standard method to evaluate cell
      death pathways and new apoptosis-modulating agents. Caspase enzymatic activity
      can be conveniently monitored with peptidic chromogenic or fluorogenic
      substrates, with certain peptide sequences imparting selectivity for certain
      caspases. The synthesis of these peptide substrates is typically carried out by
      solid-phase synthesis, a method that is not ideal for production of the gram
      quantities needed for high-throughput screening. Described herein is a facile
      method for the synthesis of the Ac-DEVD-pNA caspase-3/7 substrate using solution
      phase peptide synthesis. This protocol, involving iterative PyBOP-mediated
      couplings and Fmoc deprotections, is rapid (about 5 d), operationally simple and
      can be used to generate over 1 g of product at a fraction of the cost of the
      commercial substrate.

PMID- 20134430
TI  - Expander: from expression microarrays to networks and functions.
AB  - A major challenge in the analysis of gene expression microarray data is to
      extract meaningful biological knowledge out of the huge volume of raw data.
      Expander (EXPression ANalyzer and DisplayER) is an integrated software platform
      for the analysis of gene expression data, which is freely available for academic
      use. It is designed to support all the stages of microarray data analysis, from
      raw data normalization to inference of transcriptional regulatory networks. The
      microarray analysis described in this protocol starts with importing the data
      into Expander 5.0 and is followed by normalization and filtering. Then,
      clustering and network-based analyses are performed. The gene groups identified
      are tested for enrichment in function (based on Gene Ontology), co-regulation
      (using transcription factor and microRNA target predictions) or co-location. The
      results of each analysis step can be visualized in a number of ways. The complete
      protocol can be executed in approximately 1 h.

PMID- 20134431
TI  - Using Trawler_standalone to discover overrepresented motifs in DNA and RNA
      sequences derived from various experiments including chromatin
      immunoprecipitation.
AB  - Genome-wide location analysis has become a standard technology to unravel gene
      regulation networks. The accurate characterization of nucleotide signatures in
      sequences is key to uncovering the regulatory logic but remains a computational
      challenge. This protocol describes how to best characterize these signatures
      (motifs) using the new standalone version of Trawler, which was designed and
      optimized to analyze chromatin immunoprecipitation (ChIP) data sets. In
      particular, we describe the three main steps of Trawler_standalone (motif
      discovery, clustering and visualization) and discuss the appropriate parameters
      to be used in each step depending on the data set and the biological questions
      addressed. Compared to five other motif discovery programs, Trawler_standalone is
      in most cases the fastest algorithm to accurately predict the correct motifs
      especially for large data sets. Its running time ranges within few seconds to
      several minutes, depending on the size of the data set and the parameters used.
      This protocol is best suited for bioinformaticians seeking to use
      Trawler_standalone in a high-throughput manner.

PMID- 20134432
TI  - Experimental acute biliary pancreatitis induced by retrograde infusion of bile
      acids into the mouse pancreatic duct.
AB  - Mechanistic studies of acute pancreatitis require animal models because clinical
      material is generally not available during the early phases of the disease. Here
      we describe a protocol to induce biliary pancreatitis by retrogradely infusing
      bile acids into the pancreatic duct of anesthetized mice. The resulting model
      replicates events believed to be responsible for the onset of clinical biliary
      (i.e., gallstone) pancreatitis and creates highly reproducible pancreatitis with
      a severity that depends on the concentration of infused bile acid. Pancreatitis
      reaches its maximal level of severity within 24 h of induction, and it resolves
      over the subsequent week. This protocol enables the investigator to use
      genetically modified strains of mice, and it requires only relatively simple and
      easily learned techniques of small animal surgery. With practice and gentle
      technique, the surgery (from induction of anesthesia to completion of the
      infusion) can be completed within 25 min per animal.

PMID- 20134433
TI  - Construction and testing of engineered zinc-finger proteins for sequence-specific
      modification of mtDNA.
AB  - Engineered zinc-finger proteins (ZFPs) are hybrid proteins developed to direct
      various effector domains (EDs) of choice to predetermined DNA sequences. They are
      used to alter gene expression and to modify DNA in a sequence-specific manner in
      vivo and in vitro. Until now, ZFPs have mostly been used to target DNA sites in
      nuclear genomes. This protocol describes how to adapt engineered ZFP technology
      to specifically modify the mammalian mitochondrial genome. The first step
      describes how to construct mitochondrially targeted ZFPs (mtZFPs) so that they
      are efficiently imported into mammalian mitochondria. In the second step, methods
      to test the basic properties of mtZFPs in vitro are described. Finally, we
      outline how the mtZFPs can be transiently transfected into mammalian cells and
      their mitochondrial import tested by both immunofluorescence and biochemical
      methods. The protocol can be completed within a week, although time-consuming DNA
      cloning steps may extend this.

PMID- 20134434
TI  - Multiplexed immunophenotyping of human antigen-presenting cells in whole blood by
      polychromatic flow cytometry.
AB  - We describe two modular protocols for immunostaining and multiparameter flow
      cytometric analysis of major human antigen-presenting cells (APCs; e.g.,
      dendritic cells, monocytes and B lymphocytes) in minimally manipulated whole
      blood samples. Simultaneous detection of up to eight colors is enabled by careful
      selection and testing of cell-subset-defining monoclonal antibodies (anchor
      markers) in the appropriate fluorochrome combinations, in order to show the
      quantification of surface expression levels of molecules involved in chemotaxis
      (e.g., CX(3)CR1 and CCR2), adhesion (e.g., CD11b and CD62L), antigen presentation
      (e.g., CD83, CD86 and CD209) and immune regulation (e.g., CD101) on circulating
      APCs. Each immunostaining reaction requires as little as 50-100 microl of
      peripheral whole blood and no density-gradient separation, and the entire
      procedure from preparation of reagents to flow cytometry can be completed in <5
      h.

PMID- 20134435
TI  - Supporting data.

PMID- 20134436
TI  - WHO report on drug development marred by big pharma leak.

PMID- 20134437
TI  - Hazardous microbe rules raise biosecurity debate to a new level.

PMID- 20134439
TI  - 'Cure acceleration' funds woven into health reform legislation.

PMID- 20134442
TI  - Companies throw their weight behind new antiobesity drugs.

PMID- 20134443
TI  - Mandatory registration required for Korean stem cell lines.

PMID- 20134444
TI  - New vaccine tailored to the weakened elderly immune system.

PMID- 20134448
TI  - Outsourcing challenges FDA to strengthen oversight abroad.

PMID- 20134449
TI  - New retrospective analysis of drugs gives pregnant pause.

PMID- 20134452
TI  - Elusive claims data hold promise for healthcare research.

PMID- 20134450
TI  - Destroying newborn blood samples threatens birth defect research.

PMID- 20134454
TI  - Doping at the winter games.

PMID- 20134455
TI  - Sacked drugs advisor launches private panel.

PMID- 20134456
TI  - NIH goes back to college for peer review.

PMID- 20134458
TI  - From pond scum to pharmacy shelf.

PMID- 20134459
TI  - The search beyond statins.

PMID- 20134460
TI  - Straight talk with...Ken Getz. [Interviewed by Cassandra Willyard].
AB  - How should clinical trials be improved? Ken Getz, a senior fellow at the Tufts
      Center for the Study of Drug Development, has been thinking up answers to this
      question for two decades. In 2003, Getz took on a new challenge when he launched
      the Center for Information & Study on Clinical Research, a nonprofit focused on
      providing education and outreach on clinical research to the public. Cassandra
      Willyard asked Getz for his thoughts on trial recruitment, financial conflicts of
      interest and keeping trial participants safe.

PMID- 20134461
TI  - Calcium-modulating cyclophilin ligand does not restrict retrovirus release.

PMID- 20134462
TI  - On the origin of glioneural neoplasms after neural cell transplantation.

PMID- 20134466
TI  - Gut microbes extend reach to systemic innate immunity.

PMID- 20134467
TI  - Inflammatory proteinase slips into tumor cells.

PMID- 20134468
TI  - Gene therapy activates EVI1, destabilizes chromosomes.

PMID- 20134469
TI  - Angiotensin II and JAK2 put on the pressure.

PMID- 20134470
TI  - Empowering T helper 17 cells in autoimmunity.

PMID- 20134471
TI  - Burning fat not so sweet.

PMID- 20134472
TI  - Muscling in: Gene therapies for muscular dystrophy target RNA.
AB  - Muscle diseases can take many forms, from the progressive muscle degeneration of
      dystrophies to the childhood cancer rhabdomyosarcoma. In 'Bench to Bedside', Joel
      R. Chamberlain and Jeffrey S. Chamberlain discuss studies using antisense
      oligonucleotides to treat Duchenne muscular dystrophy and myotonic dystrophy. In
      'Bedside to Bench', Simone Hettmer and Amy J. Wagers examine the implications of
      clinical studies describing a type of rhabdomyosarcoma that resembles acute
      leukemia. The findings dovetail with other studies suggesting that some of these
      cancers might originate outside of muscle tissue and highlight the need for a
      better understanding of the cells that give rise to this condition.

PMID- 20134473
TI  - Muscling in: Uncovering the origins of rhabdomyosarcoma.

PMID- 20134478
TI  - Retraction: Identification of calcium-modulating cyclophilin ligand as a human
      host restriction to HIV-1 release overcome by Vpu.

PMID- 20134479
TI  - Antibiotic prophylaxis in oral healthcare - the agreement between Swedish
      recommendations and evidence.
AB  - BACKGROUND: Almost all (17/20) Swedish counties have pharmaceutical committees
      that establish recommendations for the use of antibiotic prophylaxis in oral
      healthcare.Objective To evaluate the evidence for the use of antibiotic
      prophylaxis in oral healthcare and the agreement between Swedish recommendations
      and evidence. MATERIAL AND METHODS: We conducted a systematic literature search
      in PubMed and the Cochrane Controlled Trials Register. The MeSH terms 'antibiotic
      prophylaxis' and 'dentistry' were used in the database search. Abstracts were
      reviewed according to specific inclusion and exclusion criteria. A total of 186
      articles were read in full text by the four authors independently. Data
      extraction and interpretation of data was carried out using a pre-defined
      protocol. In the end, one case-control study was included for evaluation of
      evidence. RESULTS: The case-control study included patients with specific cardiac
      conditions. The study reported a 49% protective efficacy (odds ratio: 0.51) of
      antibiotic prophylaxis for first-time episodes of endocarditis within 30 days of
      procedure. This result was not statistically significant. The quality of the
      evidence was low. No studies were evaluated on patients with other medical
      conditions. The recommendations included several cardiac and other medical
      conditions for which there is a lack of evidence or no evidence to support the
      use of antibiotic prophylaxis. CONCLUSIONS: There is a lack of evidence to
      support the use of antibiotic prophylaxis. To avoid the risk of adverse events
      from antibiotics and the risk of developing resistant bacterial strains, the use
      of antibiotic prophylaxis should be minimised and recommendations in Sweden
      should be revised to be more evidence-based.

PMID- 20134480
TI  - Modelling workforce skill-mix: how can dental professionals meet the needs and
      demands of older people in England?
AB  - BACKGROUND: There is an urgent need to consider the skill-mix of the dental team
      to meet the oral health needs and demands of the population in general, and older
      people in particular. As people live longer and retain their teeth there will be
      a progressive change in both the volume and type of dental care required, and the
      demand for care. Operational research modelling provides the opportunity to
      examine and test future scenarios for National Health Service (NHS) care. AIM:
      The aim of this research was to explore the required skill-mix of the dental team
      to meet future need and demand of older people in England to 2028 utilising
      operational research methods and to examine a range of future scenarios. METHOD:
      A three-stage computer model was developed to consider demand for dental care,
      workforce supply and skill-mix. First, the demand model combined population
      demography and a marker of oral health with attendance and treatment rates based
      on NHS activity data. Monte Carlo simulation was used to give an indication of
      the uncertainty surrounding this projected demand. Second, projections on
      workforce supply and other assumptions relating to clinical hours, NHS commitment
      and workforce whole time equivalents (WTEs) were analysed to produce a range of
      estimates for the current and future workforce. Third, staff skill-mix
      competencies were examined and the data fed into an optimisation model. Linear
      programming was used to give the optimal workforce makeup and predictions for
      workforce requirements. Five future scenarios were run from 'no skill-mix'
      through to 'maximum skill-mix' in the dental team, and the outputs compared.
      RESULTS: The results indicate that by 2028 there will be an increase in demand
      for care among older people of over 80% to almost 8.8 million hours; however,
      Monte Carlo simulation suggests considerable uncertainty surrounding the demand
      model outputs with demand deviating from the average in terms of treatment hours
      by as much as 22%. Modelling a healthcare system with 'no skill-mix' resulted in
      the lowest volume of clinical staff equivalents (dentists: 8,668) providing care
      for older people, whereas maximum skill-mix involved more staff (clinical staff =
      10,337, of whom 2,623 were dentists, 4,180 hygienist/therapists and 3,534
      clinical dental technicians) if all care is provided at the relevant level of
      competence. CONCLUSION: The model suggests that with widening skill-mix, dental
      care professionals can play a major role in building dental care capacity for
      older people in future. The implications for health policy, professional bodies
      and dental teamworking are discussed.

PMID- 20134481
TI  - A domesticated transposon mediates the effects of a single-nucleotide
      polymorphism responsible for enhanced muscle growth.
AB  - Single-nucleotide polymorphisms (SNPs) in the regulatory regions of the genome
      can have a profound impact on phenotype. The G3072A polymorphism in intron 3 of
      insulin-like growth factor 2 (IGF2) is implicated in higher muscle content and
      reduced fat in European pigs and is bound by a putative repressor. Here, we
      identify this repressor--which we call muscle growth regulator (MGR)--by using a
      DNA protein interaction screen based on quantitative mass spectrometry. MGR has a
      bipartite nuclear localization signal, two BED-type zinc fingers and is highly
      conserved between placental mammals. Surprisingly, the gene is located in an
      intron and belongs to the hobo-Ac-Tam3 transposase superfamily, suggesting
      regulatory use of a formerly parasitic element. In transactivation assays, MGR
      differentially represses the expression of the two SNP variants. Knockdown of MGR
      in C2C12 myoblast cells upregulates Igf2 expression and mild overexpression
      retards growth. Thus, MGR is the repressor responsible for enhanced muscle growth
      in the IGF2 G3072A polymorphism in commercially bred pigs.

PMID- 20134482
TI  - Skp2B attenuates p53 function by inhibiting prohibitin.
AB  - The F-box protein Skp2 and its isoform Skp2B are both overexpressed in breast
      cancers. Skp2 alters the activity of p53 by inhibiting its interaction with p300
      and by promoting p300 degradation. Here, we report that Skp2B also attenuates the
      activity of p53; however, this effect is independent of p300, suggesting that
      another mechanism might be involved. Prohibitin, a protein reported to activate
      p53, was isolated in a two-hybrid screen with the carboxy-terminal domain unique
      to Skp2B. We observed that prohibitin is a new substrate of Skp2B and that the
      degradation of prohibitin is responsible for the attenuated activity of p53 in
      cells overexpressing Skp2B. Furthermore, we show that the activity of p53 is
      reduced in the mammary glands of Skp2B transgenic mice. This study indicates that
      both Skp2 and Skp2B attenuate p53 activity through different pathways, suggesting
      that amplification of the Skp2 locus represents a powerful mechanism to attenuate
      p53 function in cancer.

PMID- 20134483
TI  - The expanding role of biologic therapy for IBD.

PMID- 20134484
TI  - GERD: are functional heartburn and functional dyspepsia one disorder?

PMID- 20134485
TI  - Pancreas: Is there still a role for total pancreatectomy?

PMID- 20134486
TI  - Primary sclerosing cholangitis: what is the role of ursodeoxycholic acid in
      therapy for PSC?

PMID- 20134487
TI  - Liver: Management of non-acetaminophen-induced ALF.

PMID- 20134488
TI  - Diverticular disease: what is the best long-term treatment?

PMID- 20134489
TI  - The potential for disease modification in Crohn's disease.
AB  - The natural history of Crohn's disease is characterized by progression to
      complicated and disabling disease, often necessitating surgical interventions.
      There is either circumstantial or direct evidence to support the disease
      modifying potential of several therapeutic agents. Healing of endoscopic lesions
      is an emerging surrogate marker of disease modification, as mucosal lesions are
      considered to reflect ongoing inflammation and tissue damage that lead to the
      formation of fistulas and fibrotic strictures, which are the main indications for
      surgery. In contrast to systemic steroids, both azathioprine and anti-tumor
      necrosis factor (TNF) agents have demonstrated the potential of mucosal healing.
      Prevention of hospitalization and surgery in the short and medium term has been
      demonstrated for the anti-TNF agents infliximab and adalimumab. The evidence
      supporting a role for medical therapy in the prevention of fibrotic wall
      thickening and in the obliteration of fistula tracks is limited and should be the
      focus of further prospective studies. These studies should validate predictors of
      complicated disease and randomized studies should be performed in high-risk
      groups to investigate whether early introduction of immunosuppressive agents or
      biologic therapies slows down disease progression and alters the natural history
      of the disease.

PMID- 20134490
TI  - Top-down therapy for IBD: rationale and requisite evidence.
AB  - Several trials have shown that early treatment of Crohn's disease with
      immunomodulators and anti-TNF agents leads to a superior clinical outcome,
      including healing of the mucosa, compared with standard therapy alone. Mounting
      evidence indicates that mucosal healing is associated with a reduced risk of
      complications, and a reduced need for surgeries and hospitalizations. In the
      SONIC trial, a combination of the standard azathioprine immunomodulator therapy
      and infliximab, an anti-TNF agent, had more potent anti-inflammatory effects than
      either drug alone in patients with Crohn's disease who had evidence of active
      inflammation. These findings and those from rheumatoid arthritis trials have
      prompted the investigation of early initiation of immunomodulator (standard or
      anti-TNF) therapy for Crohn's disease, in suitable patients, which has led to
      substantial improvements in disease management. Careful selection of patients is,
      however, essential given the potential risk of toxic effects from these therapies
      and the fact that some patients with IBD will have a favorable disease course
      without them. Identification of suitable patients, however, remains a challenge,
      as genetic, phenotypic and environmental factors have not yet been identified
      that can be used for routine assessment and selection is mainly based on clinical
      criteria.

PMID- 20134491
TI  - Optimizing the safety of biologic therapy for IBD.
AB  - The introduction of biologic therapy for the treatment of IBD has substantially
      changed its management. The safety concerns associated with biologic therapies
      include the increased risk of infection, autoimmunity, development of lymphoma
      and demyelinating disease, and the risk of worsening heart failure. There are
      several strategies for minimizing the risks associated with biologic therapies.
      Pretreatment strategies include taking a proper history from the patient,
      physical examination of the patient, screening for latent tuberculosis and ruling
      out sepsis. Vaccination of patients against vaccine preventable diseases is also
      recommended. During treatment, patients should be closely monitored and any
      symptoms that develop should be dealt with early. Education of physicians and
      patients is also important to allow the early detection of any adverse events.

PMID- 20134492
TI  - The pharmacoeconomics of biologic therapy for IBD.
AB  - The past decade has been marked by the introduction and expanding use of biologic
      therapies for the induction and maintenance of response in patients with IBD.
      Although widely heralded for their efficacy, these agents have also stirred
      controversy over the potential economic impact that they will have upon the
      world's health-care systems. Traditional cost analyses had shown that IBD
      medication costs contributed minimally towards the overall costs associated with
      the disease; however, these studies were all conducted before the introduction of
      biologic therapies. At that time, a small minority of patients accounted for a
      disproportionately large percentage of the overall costs, suggesting that cost
      savings could be realized if interventions decreased the utilization of health
      care resources and associated costs. More recent studies have been heterogeneous
      in their design and findings-some have suggested that cost-savings realized due
      to a decrease in the utilization of health-care services may offset the higher
      costs of biologic agents. Incorporation of data on indirect cost-savings and
      quality of life improvements into ongoing and future analyses is required to
      allow for more accurate analyses of overall costs and cost-savings.

PMID- 20134494
TI  - Erratum to: Polychrometer with Extreme Rejection of Stray Light.

PMID- 20134493
TI  - Future biologic targets for IBD: potentials and pitfalls.
AB  - The treatment of patients with IBD has evolved towards biologic therapy, which
      seeks to target specific immune and biochemical abnormalities at the molecular
      and cellular level. Multiple genes have been associated with susceptibility to
      IBD, and many of these can be linked to alterations in immune pathways. These
      immune pathways provide avenues for understanding the pathogenesis of IBD and
      suggest future drug targets, such as the IL-12-IL-23 pathway. In addition, failed
      therapeutic drug trials can provide valuable information about pitfalls in study
      design, drug delivery and disease activity assessment. Future biologic drug
      development will benefit from the early identification of subsets of patients who
      are most likely to respond to therapy by use of biological markers of genetic
      susceptibility or immunologic susceptibility.

PMID- 20134495
TI  - Laser mode locking with a glass filter.

PMID- 20134496
TI  - Moire-holography method for measuring inhomogeneous distributions of refractive
      index.

PMID- 20134497
TI  - Laser scattering induced holograms in lithium niobate.

PMID- 20134498
TI  - Applied optics of optics and opticists.

PMID- 20134499
TI  - Patents.
AB  - 3,704,937; 3,709,610; 3,712,813; 3,713,032; 3,715,164; 3,717,412; 3,717,415;
      3,725,812; 3,725,814; 3,725,817; 3,729,690; 3,729,704; 3,736,040; 3,737,212;
      3,737,231; 3,737,629; 3,743,422; 3,748,753; 3,751,132; 3,764,978; 3,786,367.

PMID- 20134501
TI  - Meeting reports.

PMID- 20134500
TI  - Symbols unit nomenclature.

PMID- 20134502
TI  - Optical activities in industry.

PMID- 20134503
TI  - Optical activities in the universities.

PMID- 20134504
TI  - Comment on: Computation of Angular Functions pi(n) and T(n) Occurring in Mie
      Theory.

PMID- 20134505
TI  - Interferometric method of measuring plotter distortion.

PMID- 20134506
TI  - Comments on: Real-Time Holographic Motion Picture Camera Capable of Recording
      Front Surface Detail from a Random Velocity Vector.

PMID- 20134508
TI  - Simple device for photomultiplier cooling.

PMID- 20134507
TI  - Performance of a michelson interferometer with asymmetric surface defects
      distribution.

PMID- 20134509
TI  - Faraday Rotator Using ED4 Glass.

PMID- 20134510
TI  - Remote temperature sounding in the presence of cloud by zenith scanning.
AB  - The principles of remote sounding of vertical temperature profiles in planetary
      atmospheres containing cloud layers are presented for an approach that uses
      measurements at different angles to the local vertical to eliminate the unknown
      cloud effects. A numerical example for a model of the earth's atmosphere shows
      that soundings separated by 40 degrees in zenith angle permit the recovery of the
      temperature profile with an error that is not significantly greater than that
      obtained in the clear atmosphere case, and without serious horizontal smear. It
      is proposed that the method will be valuable for the interpretation of
      measurements made by instruments on spin-stabilized spacecraft on planetary
      missions, since in these cases the required angular coverage is obtained
      automatically for most trajectories.

PMID- 20134511
TI  - Multiple scattering calculation of the middle ultraviolet reaching the ground.
AB  - We use a multiple channel solution to the radiative transfer equation, a
      computationally fast method which achieves reasonable accuracy. The method is
      applied to the problem of light scattering in a turbid atmosphere in the 280-340
      nm wavelength region to calculate the direct, downward diffuse and global flux
      reaching the ground. This spectral region is of particular interest in studies of
      the biological effects of possible depletion of the ozone layer by a future fleet
      of supersonic transport planes. We input atmospheric conditions in terms of
      analytic models chosen to encompass standard ozone and aerosol distributions.We
      examine the changes in the results with respect to the variations of the solar
      zenith angle, wavelength ozone thickness, aerosol thickness, ground albedo, and
      ground height level. The results are fairly well represented by a semiempirical
      analytic formula which may be used for the purposes of interpolation and
      communication.

PMID- 20134512
TI  - Atmospheric turbulence effects on the phase of laser beams.
AB  - Measurements of the phase structure function of a laser beam propagated through
      the turbulent atmosphere along two different paths are reported. The first path
      was chosen in an urban zone, the second one was along a flat and quiet region. A
      comparison of the results with the theoretical predictions of Tatarsky and
      Lutomirsky and Yura is made. A discussion of the range of validity of the
      theoretical treatments is presented.

PMID- 20134513
TI  - Infrared absorption by small amorphous quartz spheres.
AB  - Optical constants for fused quartz were determined from 1400 cm(-1) to 400 cm(
      1). Three absorption bands were observed in the infrared for amorphous quartz
      powder dispersed in KBr. These same bands, somewhat altered in shape and in peak
      position, were seen in amorphous SiO(2) smoke particles in air. Two of these
      bands were determined to be due to surface modes. Measurements agreed well with
      calculated peak positions and relative peak heights, but were broader and lower
      than those predicted by theory. The observed broadening could not be attributed
      to the size or shape of the individual particles.

PMID- 20134514
TI  - Sensitivity of the Ellipsometric Parameters to Angle-of-Incidence Variations.
AB  - Formulas by which the partial derivatives of the ellipsometric parameters psi and
      Delta with respect to the angle of incidence can be calculated are presented.
      These derivatives are plotted as a function of the angle of incidence, the
      refractive indices of the film, the substrate, and the immersion medium, and also
      as a function of film thickness on three-dimensional graphs. These graphs
      illustrate the angular regions in which angle-of-incidence errors are significant
      for typical materials. At the angles of incidence at which these derivatives are
      large, errors due to beam deviation and errors due to the use of noncollimated
      light or due to the use of specimens with rough or irregular surfaces can be
      significant. The results illustrate that the errors due to beam deviation are
      often significant in zone-averaged measurements when standard optical components
      with wedge angle tolerances of 0 degrees 3' of arc are used.

PMID- 20134515
TI  - Refractive Index Determination of Layered Compound ZnIn(2)S(4).
AB  - Refractive index measurements of layer structure crystals of ZnIn(2)S(4) were
      performed over the 0.45-1.25 microm wavelength range. An improved interferometric
      method that allowed a precision of 0.2% in the n(lambda) values was used.

PMID- 20134516
TI  - Effects of changing canopy directional reflectance on feature selection.
AB  - A Monte Carlo model was used to predict the mean apparent directional reflectance
      of a simulated plant canopy and the covariance for seven wavelength channels in
      the visible portion of the spectrum. The non-Lambertian spectral response from
      Bouteloua gracilis canopies possessing two plant cover densities was simulated
      for two solar positions. The calculated spectral signatures as a function of look
      angle were then analyzed using the divergence criteria to select the best two
      wavelength channels for discrimination. These calculations indicate that
      different combinations of wavelength channels are appropriate for various sensor
      look angles, that target signatures have greater statistical separation for some
      scan angles than others, and that these effects are time varying.

PMID- 20134517
TI  - Pieges a lumiere interferentiels a larges bandes azimuthale et spectrale.
AB  - Optical interference coatings are designed that provide a very low reflectance
      and thus can be used to reduce parasitic flux in optical systems. They consist of
      alternate layers of magnesium fluoride and thin aluminum and reduce the radiant
      reflectance to less than 1% over a 80-nm spectral bandwidth.

PMID- 20134518
TI  - Pulsed dye laser system for Raman and luminescence spectroscopy.
AB  - A spectroscopic system using a pulsed dye laser to measure Raman scattering and
      luminescence spectra in solids is described. The dye laser, which is pumped by a
      pulsed nitrogen laser, is capable of being continuously tuned throughout the
      visible and near ultraviolet regions of the spectrum. The detection system uses
      gated photon counting, synchronized to the laser pulses. The apparatus combines a
      greater tuning range than that obtained using cw dye lasers with enhanced
      sensitivity over pulsed systems using analogue detection.

PMID- 20134519
TI  - Collector Size or Range Independence of SNR in Fixed-Focus Remote Raman
      Spectrometry.
AB  - When sensitivity allows, remote Raman spectrometers can be operated at a fixed
      focus with purely electronic (easily multiplexable) range gating. To keep the
      background small, the system etendue must be minimized. For a maximum range
      larger than the hyperfocal one, this is done by focusing the system at roughly
      twice the minimum range at which etendue matching is still required. Under these
      conditions the etendue varies as the fourth power of the collector diameter,
      causing the background shot noise to vary as its square. As the signal also
      varies with the same power, and background noise is usually limiting in this type
      instrument, the SNR becomes independent of the collector size. Below this minimum
      etendue-matched range, the transmission at the limiting aperture grows with the
      square of the range, canceling the inverse square loss of signal with range. The
      SNR is thus range independent below the minimum etendue matched range and
      collector size independent above it, with the location of transition being
      determined by the system etendue and collector diameter. The range of validity of
      these outrageousstatements is discussed.

PMID- 20134520
TI  - High Resolution Infrared Spectrometer in the 8-10-microm Range.
AB  - A double pass SISAM interferometer is presented. Its resolving power is close to
      0.011 cm(-1) Accurate q(u) constants of 11(1)0 and 03(1)0 levels of N(2)O are
      calculated using the first spectra recorded.

PMID- 20134521
TI  - Variable magnification spectrometer.
AB  - A new high-speed spectrometer has been designed for the measurement of line
      profiles emitted by pulsed plasmas. This spectrometer, with a Fabry-Perot as
      disperser, presents the essential advantage of possessing an electronic radial
      scanning, without any mechanical elements. Moreover, the simplicity of the
      device, the direct visualization of the storage are other advantages.

PMID- 20134522
TI  - Linear pressure tuning of a multielement dye laser spectrometer.
AB  - Construction details and operating characteristics are given for a narrowband
      pulsed dye laser system, pumped by a nitrogen laser, that offers very linear
      reproducible frequency tuning over continuous ranges of 150 GHz and more, at a
      bandwidth down to 25 MHz. A diffraction grating in Littrow configuration, a
      tilted Fabry-Perot interferometer inside the cavity, and an optical external
      confocal filter interferometer are the wavelength-selective elements.
      Simultaneous scanning of these elements is accomplished without mechanically
      moving parts by changing the gas pressure in an enclosing chamber.

PMID- 20134523
TI  - Optical beam shaping devices using polarization effects.
AB  - Devices with radially varying transmission characteristics, based upon control of
      the polarization of monochromatic light passing through them, have been designed,
      constructed, and experimentally evaluated. The significance of such devices to
      beam shaping in large beam diameter, high-energy laser systems is mentioned.

PMID- 20134524
TI  - Methods for optimizing the beam shape in a focused coherent optical system.
AB  - A laser beam can be altered in a number of ways to achieve a desired intensity
      distribution in the focal plane of an optical system. Both active and passive
      means are discussed. Optimization of the SNR in an optical memory application has
      been analyzed, and experimental results are presented illustrating the
      effectiveness of the methods.

PMID- 20134525
TI  - Coaxial alignment of laser beams for perturbation experiments.
AB  - An instrument is described for the coaxial alignment of two laser beams, one of
      which is a continuous wave helium-neon laser, the other one a pulsed neodynium
      glass laser. The helium-neon laser beam is aligned such that it propagates in the
      axis of the pulsed laser beam and thus permits observation of changes before,
      during, and after the occurrence of the pulsed laser event. Although the design
      emphasized the 1.35-mu sidebands of the neodymium laser, most tests were
      conducted at 1.06 mu, where neodymium in glass ordinarily operates. A residual
      nonlinearly polarized component of the pulsed laser light caused considerable
      disturbance in the detection circuit and prevented low level detection of
      perturbation effects.

PMID- 20134526
TI  - Interferometric angular measurement.
AB  - An interferometer designed to measure and/or generate angles with high precision
      and accuracy is described. Design criteria and equations are developed and the
      experimental performance of a prototype interferometer is discussed.

PMID- 20134527
TI  - Spectrophotometers for the measurement of light in polar ice and snow.
AB  - Two portable spectrophotometers have been designed to record light scattering and
      absorption in polar ice and snow. In the first instrument optical fibers are used
      to transmit light from the interior of the ice to the spectrophotometer. Such an
      arrangement allows light measurements up to 2 m away from the instrumentation
      with minimal disturbance of the natural environment. A miniaturized, submersible
      spectrophotometer was also built for in situ measurements under floating sea ice.
      This version, except for the recording apparatus, is entirely self-contained and
      is housed in a cylindrical tube 9 cm in diameter and 60 cm in length. The unit
      can be lowered into the ocean through a small borehole in the ice; position and
      orientation are controlled from the surface. Both spectrophotometers are designed
      to measure light intensities in the visible spectrum (400-1000 nm). Wavelength
      resolution is adjustable down to 8 nm at a wavelength of 400 nm, with a field of
      view of less than 3 degrees . Sensitivities in the pr sent versions are
      sufficient for measurements through several meters of sea ice with a relative
      accuracy of 1%. Instrument operation has been tested in the Arctic down to
      temperatures of -25 degrees C.

PMID- 20134528
TI  - Interferometric Null Method for Measuring Stress-induced Birefringence.
AB  - A sensitive apparatus utilizing a scanning Fabry-Perot interferometer excited by
      circularly polarized laser radiation is developed for measuring birefringence. A
      birefringent sample within the interferometer produces a difference in the
      resonance length for radiation polarized in two orthogonal directions. A Kerr
      cell properly oriented within the interferometer is used to cancel sample
      birefringence by adjusting the cell voltage. This adjustment is made by using the
      scanning interferometer as a spectrum analyzer and observing the displacement
      between the resonance curves associated with each polarization. The Kerr cell is
      calibrated in terms of the voltage required to produce a relative path
      retardation of lambda/2. The stress-induced birefringence in YAG, sapphire, and
      fused silica in the 26-75 degrees C temperature range is measured, and the
      accuracy and sensitivity of the instrument are assessed.

PMID- 20134529
TI  - Matrix multiplication using incoherent optical techniques.
AB  - The use of incoherent electrooptical analog methods for performing matrix-vector
      multiplication has been investigated mathematically. A technique for encoding the
      matrix information on a two-dimensional binary optical transparency by means of
      an area modulation scheme is described. The one-dimensional discrete finite
      Fourier transform, viewed from the standpoint of matrix-vector multiplication,
      has been performed experimentally to demonstrate feasibility. Matrix and vector
      array sizes employed were 33 x 33 and 33 x 1, respectively. The average value of
      the correlation coefficients between theoretically derived andexperimental data
      was found to be 0.95.

PMID- 20134530
TI  - Binary synthetic holograms.
AB  - The positions and width of the fringes in a binary synthetic hologram are
      determined by the points at (x,y) that satisfy -q/2 </= x/T + Phi (x,y)/2pi + n
      </= q/2, where Phi(x,y) is the phase variation of the wavefront, T is the grating
      period, n is an integer, and q is a constant determining the fringe width. A
      method for finding an exact solution to this inequality is presented. The
      feasibility of the procedure has been tested by making binary synthetic
      holograms. Experimental results are presented, and extensions of the method are
      discussed.

PMID- 20134531
TI  - Fabrication of aspherics using a mathematical model for material removal.
AB  - A mathematica model has been developed that predicts the aspheric surface that a
      typical optical surfacing machine will produce. The model, which combines two
      basic assumptions concerning material wear with the kinematics of the machine,
      has been verified experimentally for the grinding process. In regions of the
      surface where the tool extends beyond the edge of the workpiece, pressure becomes
      nonuniform, and the model must be altered. The established model has been used to
      synthesize those machine strokes required to produce a desired aspheric surface.

PMID- 20134532
TI  - The mangin mirror and its primary aberrations.
AB  - Analytical expressions have been developed for the primary aberrations of the
      thin Mangin mirror. The surface contributions for spherical aberration, coma,
      astigmatism, and field curvature are stated, including the first-order transverse
      axial chromatic aberration. Even though the Mangin mirror is used mostly with a
      large relative aperture, where higher order aberrations and residual spherical
      zonal aberration may have to be considered, the third-order expressions will
      still provide a good approximation of the image quality. This is especially true
      when the angular field coverage is modest, and the spectral bandpass of interest
      is narrow. It has been demonstrated that the Mangin mirror rates very favorably
      when compared against other single optical elements.

PMID- 20134533
TI  - Gratings for integrated optics by electron lithography.
AB  - The electron lithographic fabrication of high quality diffraction gratings with
      periods in the 0.25-microm < a(o) < 1.5-microm range is reported. The negative
      electron resist employed is a copolymer of glycidyl methacrylate and ethyl
      acrylate with a sensitivity about 15 times better than that of poly(methyl
      methacrylate), a positive resist. A new scan generator with linearity accurate to
      1 part in 10(4) and locked onto the 60-Hz power supplies is described. Gratings
      with up to 3000 lines were fabricated with long range order deltaa(o)/a(o) </= 5
      </= 10(-4). The use of the negative resist gratings as couplers for thin-slab
      dielectric waveguides is demonstrated. It was found that efficiencies up to 20%
      could be obtained in the range 0.5 < lambda(o)/a(o) < 1.1.

PMID- 20134534
TI  - Screen patterns used in reproduction of continuous-tone graphics.
AB  - There are many ways of displaying a video signal derived from graphical material.
      People in the graphic arts business have been wrestling with the same sorts of
      problems for more than 100 years; this article surveys what they have done, in
      the hope that some useful technology transfer may occur.

PMID- 20134535
TI  - Limits to the detection of small internal voids in solids with holographic
      techniques.
AB  - The ability to find small voids in acoustically excited solid specimens using
      coherent optical detection methods is limited by three factors: available
      ultrasonic power levels; noise elements; and nonlinear properties of the working
      materials. Detection sensitivity constraints due to power limitations are
      established here. A void embedded in an elastic half-space is used as a physical
      model. Free surface deformations due to internal void-scattered ultrasonic waves
      are computed for select cases. Deformations are too small for direct optical
      measurement. Deflections of a liquid layer free surface above the elastic
      halfspace represent an amplified copy of the elastic boundary deformation and
      improved detection sensitivity. Holographic techniques with noise reduction
      features to observe the liquid surface profile are discussed.

PMID- 20134536
TI  - The Reflaxicon, a New Reflective Optical Element, and Some Applications: Author's
      Reply to Comment.

PMID- 20134537
TI  - Fourier Transform vs Hadamard Transform Spectroscopy: Authors' Reply to Comments.

PMID- 20134538
TI  - Methode d'echantillonage des fonctions deterministes en spectroscopie:
      application a un spectrometre multicanal par comptage photonique. Erratum.

PMID- 20134539
TI  - Focused multiple-pass cells for Raman scattering: authors' reply to comment.

PMID- 20134540
TI  - How about radiance response?

PMID- 20134541
TI  - Applied OpticsOf Optics and Opticists.

PMID- 20134542
TI  - Parents.
AB  - 3,587,301; 3,592,549; 3,597,091; 3,628,038; 3,628,848; 3,628,866; 3,628,869;
      3,630,625; 3,631,526; 3,635,563; 3,636,360; 3,734,624; 3,746,873; 3,749,497;
      3,757,123; 3,757,127; 3,762,819; 3,784,283; 3,784,284; 3,784,285; 3,784,286;
      3,784,831; 3,786,262; 3,788,727; 3,790,254; 3,790,255; 3,790,795; 3,790,799;
      3,792,275;

PMID- 20134543
TI  - Simple technique to suppress spurious luminescence in Raman spectroscopy.

PMID- 20134544
TI  - Economical Multispectral Sun Photometer for Measurements of Aerosol Extinction
      from 0.44 mum to 1.6 mum and Precipitable Water.

PMID- 20134545
TI  - Why the sinc Function Should be Defined as (sinx) /x and not (sinpix) /pix
      Comments.

PMID- 20134546
TI  - Optical activities in industry.

PMID- 20134547
TI  - Focused multiple-pass cell for Raman scattering: comment.

PMID- 20134549
TI  - Small absorption coefficient measurement by calorimetric and spectral emittance
      techniques.

PMID- 20134548
TI  - Spectral interval, photoelectric effect, and variance.

PMID- 20134550
TI  - Mass absorption coefficients for polypropylene and parylene C between 8.34 a and
      452 a.

PMID- 20134551
TI  - Atmospheric corrections for airborne measurements of water surface temperature.

PMID- 20134553
TI  - Application of a simple differential interferometer to high current arc
      discharges.

PMID- 20134552
TI  - Fabry-perot interferometer applied to optical derivative spectroscopy at low
      light levels.

PMID- 20134554
TI  - Photoactivated twisted nematic device.

PMID- 20134555
TI  - Optical waveguiding polarizer.

PMID- 20134556
TI  - Multimode waveguide: a low-pass filter; supplementary comments.

PMID- 20134558
TI  - Drawn pitch threads as masks for microfabrication.

PMID- 20134557
TI  - Electronically scanned waveguide laser arrays.

PMID- 20134559
TI  - Low threshold coaxial n(2) laser with a resonator.

PMID- 20134560
TI  - Production of stress waves with nanosecond laser pulses.

PMID- 20134561
TI  - Imaging properties of a conic axicon.

PMID- 20134562
TI  - The reflaxicon, a new reflective optical element, and some applications: comment.

PMID- 20134563
TI  - Family of compact schmidt-cassegrain telescope designs.

PMID- 20134564
TI  - Two well-corrected four-mirror telescopes.

PMID- 20134565
TI  - Diffraction images of truncated triangular wave objects formed by a polarizing
      microscope with crossed polarizers.

PMID- 20134566
TI  - Energy Distribution in the PSF for an Arbitrary, Passband.

PMID- 20134567
TI  - Real-time holographic motion picture camera capable of recording front surface
      detail from a random velocity vector: erratum.

PMID- 20134568
TI  - Screen test for large mirrors.
AB  - A shop method for testing large mirrors using a square-array sampling screen has
      been developed. The main features of this method are simple test setup
      independent of random air turbulence, high surface sampling rate, reliability and
      repeatability of results, detection of surface departures +/-0.1lambda (at 5000
      A) or greater from the ideal surface, and self-calibration. Only large-area
      departures can be accurately detected by this method.

PMID- 20134569
TI  - Null ronchi test for aspherical surfaces.
AB  - A new kind of null Ronchi test for aspherical surfaces is devised using a special
      ruling with curved lines. This test is found to be more advantageous for
      aspherical surfaces that the normal Ronchi test, which depends solely on
      computation to determine the shape of the fringes on the surface. The only
      restriction on this test is that a point source must be used.

PMID- 20134570
TI  - Mathematical interpretation of radial shearing interferometers.
AB  - The procedure for computing a radial shearing interferometric pattern is given.
      The interferometric pattern is analyzed to obtain the wavefront shape.
      Restricting the discussion to wavefronts having rotational symmetry, we give two
      different methods of finding the wavefront. One approach is to scan along a
      diameter of the interferometric pattern and the other is to examine the shape of
      the fringes. The relative sensitivity of a radial shearing interferometer with
      respect to that of a Twyman-Green interferometer is also analyzed.

PMID- 20134571
TI  - Stellar interferometer for figure sensing of orbiting astronomical telescopes.
AB  - An interferometric device designed to be located in the focal plane of a large
      astronomical telescope is presented. The prime application is for the forthcoming
      large space telescope. The device is to perform interferometry on the optical
      wavefront arising from a single star after it has propagated through the
      telescope. The concept of a focal plane figure sensor has been experimentally
      verified by fabricating and testing an operating laboratory breadboard figure
      sensor. A set of linear independent control equations are derived that define the
      operations for utilizing a focal plane figure sensor in the control loops for the
      positioning of the secondary mirror and for the active control of the primary
      mirror optical figure. A number of scientific experiments that could be preformed
      with the interferometer are also briefly discussed.

PMID- 20134572
TI  - Nonlinear resonance scanning.
AB  - A new scanning concept is suggested for causing a flat mirror (or telescope) to
      execute a symmetric sawtooth scan pattern. The concept is based on the use of a
      pair of control moment gyros whose spin axes are synchronously counterrotated. If
      these gyros are mounted on the back of the mirror, then through the nonlinear
      interactions associated with the counterrotation of the spin axes of the pair of
      gyros, the mirror will be caused to scan back and forth through a symmetric
      sawtooth pattern without external drive being required. By careful choice of the
      parameters of the control moment gyros, scan efficiencies of the order of 90% can
      be achieved. This scanner concept has the virtues not only of high scan
      efficiency but also of requiring very little power and not reaching back on the
      scanner mount. It therefore seems particularly well suited for use in space
      applications. In this paper, the concept is described in detail and an
      explanation of the principles of operation is presented. An approximate analysis
      is worked out to provide an insight into the significance of the various design
      parameters. Finally, an exact analysis is presented and detailed computer
      calculations of the expected scan performance for a particular case are carried
      out.

PMID- 20134573
TI  - Nematic liquid crystal digital light deflector.
AB  - We report the principle of a new type of digital light deflector utilizing the
      electrooptic effect of index modulation in nematic liquid crystals and the
      results of the optical tests that were performed on this device. Optical
      efficiencies and contrasts, electrical operating conditions, and subsequent
      turnon times are given. A further experiment concerning the deflection of a
      colored image in incoherent white light is described, which shows that this
      device seems to be the more interesting for a lot of applications, especially
      portable ones.

PMID- 20134574
TI  - Instrumentation optimization in fourier spectroscopy. 1: far infrared beam
      splitters.
AB  - Computations of the reflectivity, transmissivity, and efficiency properties for
      TE, TM, and T45 degrees waves of far ir beam splitters (BS) and of the
      polarizations induced at both reflection and transmission are described. Effects
      of variations in the state of polarization, orientation, pointing accuracy, and
      wavelength of the incident light, as well as variations in refractive index and
      thickness of the BS, are discussed. These results apply directly to Fourier
      interferometer-spectrometers. They can be used for optimizingthe performance of
      these instruments. They indicate, in particular, that some advantages may
      begained by the use of incident polarized light (angle of polarization smaller
      than about 45 degrees or negative elliptical polarization) or light of large
      incidence angle (larger than approximately 60 degrees ) or both. A novel method
      of inversion of experimental results to the end of determining the BS physical
      parameters is proposed. It makes use of the variations with incident light
      direction of the BS reflectivity, transmissivity, or efficiency curves.

PMID- 20134575
TI  - Diffraction effects in long path interferometers.
AB  - Diffraction caused by finite apertures in long baseline interferometers leads to
      a significant loss of signal, decreased fringe visibility, and a phase shift in
      the interference pattern. Formulas are developed for the general case of an
      interferometer with unequal path lengths for monochromatic plane wave
      illumination. Numerical results are given for a range of path lengths. The
      consequences of diffraction on the performance of long path instruments,
      particularly with reference to a long baseline Michelson stellar interferometer,
      are discussed.

PMID- 20134576
TI  - Imaging performance of annular apertures.
AB  - Images formed by aberration free optical systems with annular apertures are
      investigated in the whole range of central obstruction ratios. Annular apertures
      form images with central and surrounding ring groups, and the number of rings in
      each group is given by the outer diameter of the annular aperture divided by the
      width of the annulus. The theoretical energy fraction of 0.838 in the Airy disk
      of the unobstructed aperture increases to 0.903 in the central ring groups.
      Furthermore it is shown that the energy fractions for the central and surrounding
      ring groups are constant for all obstruction ratios and in each fractional energy
      level. The central image spot in the central ring group contains only a small
      energy fraction and therefore the central ring group as a whole is the effective
      image element.

PMID- 20134577
TI  - Estimation of the location of an optical object with photodetectors limited by
      quantum noise.
AB  - We study the maximum likelihood estimation of the location of an incoherent
      object, the light from which is distorted by an optical system and detected by
      photoelectric detectors with quantum noise. The noise is treated as a set of
      uncorrelated Gaussian variables with variances proportional to the signal plus
      background at their corresponding detectors. By the simulation of the noise, a
      large number of cases are tested and curves for the probability distribution of
      the error distance are obtained.

PMID- 20134578
TI  - Image analysis using enhanced spatial correlation functions.
AB  - By enhancing the high frequencies of the irradiance spectrum of a scene, it is
      possible to reconstruct an enhanced self-correlation function that clearly
      delineates its nondifferentiable regions. The technique has application in image
      analysis and pattern recognition. By way of example, the enhanced self
      correlation function of a certain random process is furnished. Easily discernible
      are certain periodicities not apparent in the sample functions of the original
      process.

PMID- 20134579
TI  - Trade off between resolution and noise in restoration by superposition of images.
AB  - The inversion technique of Backus and Gilbert is applied to the problem of
      restoration of optical objects by superposition of images. The problem is
      formulated in the general case of space-variant systems. Curves for the trade off
      between resolution and noise in restoring objects degraded by simple diffraction
      and susceptible to uncorrelated noise are obtained. The technique is used to
      restore a test object whose image is sampled at the Nyquist rate and to which
      noise (simulated on a computer) is added. Restorations corresponding to several
      points on the trade-off curve are obtained.

PMID- 20134580
TI  - Dependence of incoherent system response on object contrast.
AB  - A relationship between the image contrast and the object contrast for a general
      periodic or a truncated periodic object is derived. The result is illustrated for
      a periodic object of rectangular wave profile. It has been shown that for a
      truncated sine wave object the image contrast bears a nonlinear relationship to
      the object contrast. The contrast dependence of the measured or the apparent
      transfer function defined as the ratio of the image contrast to object contrast
      has been investigated.

PMID- 20134581
TI  - Combination moisture resistant and antireflection plasma polymerized thin films
      for optical coatings.
AB  - The technique of plasma polymerization under vacuum conditions at ~0.1 Torr has
      been employed to produce highly moisture resistant, thin polymer films on
      hygroscopic alkali metal halide crystal materials. The polymer film is
      fluorocarbon in nature. In addition to the moisture resistance, the films also
      exhibit antireflection properties and have only one absorption band over the
      range 25,000-250 cm(-1) centered at 1200 cm(-1).

PMID- 20134582
TI  - Offset prism for optical waveguide coupling.
AB  - High refractive index prisms have been used to couple optical beams into the thin
      film waveguides. To scan through various propagating modes normally requires
      rotating and repositioning of the prism-waveguide assembly. We have found that
      the required adjustment of the prism-position can be eliminated during the
      scanning of the various modes if the prism is properly offset with respect to the
      rotational axis. An analysis and a computer program are given for the calculation
      of this prism offset position on the basis of minimum deviation within the
      specified limits of the prism rotational angle.

PMID- 20134583
TI  - Aperiodic distributed-parameter waveguides for integrated optics.
AB  - Aperiodic distributed-parameter waveguides are considered for use as reflectors
      and filters in integrated optics. Coupled-mode theory is used to predict the
      effects on modal propagation of aperiodic perturbations induced in a slab
      waveguide. In particular, it is shown that aperiodic perturbations can couple
      forward-traveling bound modes to backward-traveling bound modes; and that the
      frequency dependence of such a coupling process can be controlled through the
      aperiodicity. It is suggested that aperiodic coupling may be used to realize
      optical-waveguide reflectors and filters having predetermined spectral-response
      characteristics. As examples, the spectral-response characteristics of a narrow
      band-stop filter, a broadband-stop filter, and a narrow band-pass filter are
      calculated and presented.

PMID- 20134584
TI  - Scaling rules for thin-film optical waveguides.
AB  - An asymmetry measure is introduced to characterize thin-film optical waveguides
      that are asymmetric in refractive index. Together with the usual normalized
      frequency this allows the plotting of universal charts from which the guide
      cutoff, the effective guide index, and the effective guide thickness can be
      determined by the use of simple scaling rules. The minimum value of the effective
      guide thickness is found to be a simple function of wavelength and the film and
      substrate indices.

PMID- 20134585
TI  - Method for optimized design of dielectric multilayer filters.
AB  - A method that can be easily programmed on a digital computer is presented for
      optimizing the design of dielectric multilayer filters. Certain rules have been
      formulated to allow one to construct the electric field transmittance explicitly
      for any thin film filter system. From the spectral distribution of transmittance
      functions, one can numerically choose the layer thickness to match the prescribed
      filter frequency spectrum, assuming that the refractive index of each layer is
      given. A synthesis procedure has been proposed in this paper for the filters that
      are composed of nondispersive and nonabsorptive stacks.

PMID- 20134586
TI  - Tolerance to the phase-matching condition for the integrated acoustooptic filter.
AB  - An analysis on the tolerance to the phase-matching condition for the integrated
      acoustooptic filter using coupling of TE(0) and TE(1) modes is presented. It is
      found that at a film thickness near cutoff, the tolerance in the film surface
      variation is relatively large; however, the tolerance in the film index variation
      may cause serious problems. It is also shown that at this thickness, the
      transverse spatial coupling constant for the mode conversion is at its maximum.

PMID- 20134587
TI  - Laser-Doppler velocimeter measurements in nonuniform flow: error estimates.
AB  - An approximate technique is described for estimating errors in velocity
      measurements obtained by laser- Doppler velocimeter (LDV) techniques due to flow
      variation within the finite dimensions of the scattering volume. The analysis is
      applicable to steady laminar or turbulent velocity profiles of arbitrary form. By
      suitable adjustments in the evaluation of the equations, the technique is also
      applicable to both cw and individual realization LDV applications. In the LDV
      technique, the velocities of many particles are observed, either simultaneously
      or sequentially depending on the particle concentration. The velocity measured at
      a point is thus some type of mean velocity that is not necessarily equal to the
      velocity at the center of the scattering volume. The analysis presents a
      mathematical model for approximating the above averaging process from which
      estimates of errors in LDV measurements are obtained due to a nonuniform velocity
      distribution within the scattering volume. In addition, the analysis is extended
      to allow estimation of errors obtained when velocity measurements are made at
      locations sufficiently near the wall that part of the scattering volume is
      truncated by the wall. Example calculations are presented for an arbitrary second
      order velocity profile, for laminar parabolic flow, and for turbulent flow in a
      pipe for both cw and individual realization signals.

PMID- 20134588
TI  - Spatial and temporal power transfer measurements on a low-loss optical waveguide.
AB  - Experimental measurements of the spatial and temporal transfer of power of a 225
      m length of low-loss optical waveguide have been made. In particular, measurement
      of the angular attenuation showed substantial loss of the high order modes, which
      reflected itself in an ~8.2 nsec/km decrease in measured dispersion. Additionally
      there was a reduction of the effective numerical aperture from 0.15 to 0.12.
      Negligible mode coupling was observed in this particular waveguide, which allowed
      a phenomenological calculation of temporal output for an assumed uniform
      excitation of all modes. This agreed well with experimental measurements.
      Calculation of this output from knowledge of the index profile is presently not
      in agreement, and some possible reasons are indicated.

PMID- 20134589
TI  - Light acceptance property of an optical fiber.
AB  - A set of curves is presented and discussed for the power in dielectric rod
      trapped modes launched by a coherent or highly collimated beam incident obliquely
      on the end of the rod. The parameters used include those of importance for
      modeling visual photoreceptors.

PMID- 20134590
TI  - Excitation of fundamental and low-order modes of optical fiber waveguides by
      gaussian beams. 1: tilted beams.
AB  - The optimum condition for coupling energy into an optical fiber waveguide is
      theoretically computed for an incident beam with a Gaussian intensity
      distribution and a curved wavefront. The dependence of the modal excitation
      efficiencies on the tilt angle of the incident beam and on the refractive index
      difference of core and cladding is discussed. Numerical results show that maximum
      efficiency for the HE(11) mode can be achieved when the beam radius is chosen to
      be approximately 0.65 times the core radius. Excitation efficiencies of low-order
      modes, HE(1m) (m >/= 2) approach 80% at their cutoff when the beam size is
      suitably larger than the core diameter.

PMID- 20134592
TI  - Light scattering from elliptical fibers.
AB  - The ellipticity of the cross section of an unclad fiber can be obtained by
      observing the pattern of backscattered laser light that is incident at right
      angles to the fiber axis. The backscattered band of light has a definite width
      that depends on the ellipticity and relative orientation of the fiber. By
      observing the width and the shift of the band of backscattered light as a
      function of fiber orientation the ellipticity of the fiber cross section can be
      determined with the help of plots given in this paper.

PMID- 20134591
TI  - Integrating sphere for measuring scattering loss in optical fiber waveguides.
AB  - An integrating sphere for light scattered from fused silica optical fiber
      waveguides that is relatively simple to construct and easy to use is described.
      The novel feature is the use of a solid sphere of fused silica to facilitate
      coupling the scattered light out of the fiber cladding into the detector. The
      fiber is inserted into a slot in the sphere, and glycerine is used to index match
      between the fiber and sphere. The sphere is coated with high reflectivity barium
      sulfate, and a silicon photodiode detects the radiation in the sphere. The
      construction, operation, and performance tests on the sphere are described.

PMID- 20134593
TI  - Focused Beam and Atmospheric Coherence Measurements at 10.6 microm and 0.63
      microm.
AB  - Measurements of focused spot characteristics and the atmospheric modulation
      transfer function (MTF) over a 5.4-km horizontal path with laser light at 10.6
      microm and 0.63 microm are reported. The atmospheric coherence diameter has been
      shown to be proportional to lambda(6/5) in verification of theory. The
      atmospherically degraded long-exposure 10.6-microm spot shape was Gaussian, and
      the spot wander exhibited a stronger dependence on turbulence strength relative
      to spot blur than was theoretically predicted. The diurnal cycle of the 10.6
      microm spot characteristics and of the 10.6- and 0.63-microm atmospheric MTF's
      under clear-sky conditions were also observed.

PMID- 20134594
TI  - Detection of airborne particles using optical extinction measurements.
AB  - A method for obtaining real-time size distributions of airborne particles is
      discussed, and experimental sensitivity measurements are presented. By detecting
      the transmitted power of a low noise He-Ne laser, the optical extinction cross
      sections of individual particles are measured as they flow through the focused
      beam. Calculations for various absorbing materials show the extinction cross
      sections are from one to more than two orders of magnitude larger than their
      scattering cross sections for particle diameters in the 0.02-0.2-microm range.
      Sensitivity calculations and measurements indicate extinction cross sections down
      to 2 x 10(-12) cm (2) can be detected. This suggests absorbing particles as small
      as 0.04-microm diam can be measured using this technique.

PMID- 20134595
TI  - Measurements of Small Signal Absorption at High Temperature for the 001-100 Band
      of CO(2).
AB  - Measurements have been made of the small signal absorption of CO(2) laser
      radiation by pure heated carbon dioxide at temperatures up to 615 K. Measurements
      were made of the P12 through P26 lines in the 001-100 absorption band. The
      absorption was higher on all lines measured than is predicted assuming no
      contribution from other lines. The absorption is predicted, however, when account
      is taken of contributions due to the 01(1)1-11(1)0 band.

PMID- 20134596
TI  - Measurement of the absorption coefficient of atmospheric dust.
AB  - A method developed by previous workers for measuring the absorption coefficient
      of strongly absorbing powdered materials has been applied to samples of
      atmospheric dust in the 0.3-1.1-microm wavelength interval. This work, which is
      based on the Kubelka-Munk theory of diffuse reflectance, provides an estimate of
      the optical absorption coefficient. The corresponding imaginary refractive index
      is calculated from this value. Results are given for several samples of dry
      atmospheric dust collected in the desert of southern New Mexico. A typical value
      for the imaginary refractive index was found to be 0.007 at 0.6 microm, with
      little dependence on wavelength in the spectral range investigated. These results
      are found to be in good agreement with those of other workers obtained by
      different methods.

PMID- 20134597
TI  - Backscattered short pulse response of surface waves from dielectric spheres.
AB  - A short pulse response for surface waves involved in the backscattering by
      dielectric spheres is considered in the time domain. Since the surface-wave
      contributions for the cw backscattering are known, pulse returns for the surface
      waves are obtained from the cw solutions by Fourier synthesis. Large savings in
      computation time for a Fourier series were realized with the use of the fast
      Fourier transform algorithm. The return positions in the short pulse response can
      be approximately estimated from a scattering model for surface waves depicted by
      Van de Hulst. With the propagation constant in the dielectric sphere rather than
      in free space for a wave traveling along the sphere surface, a better agreement
      between the predicted and calculated positions for the short pulse returns was
      obtained. Significant returns of surface waves for the backscattering come from
      the surface waves that have made the maximum number of shortcuts possible through
      the sphere.

PMID- 20134598
TI  - Low-angle laser light scattering - rayleigh factors and depolarization ratios.
AB  - The Rayleigh factors and depolarization ratios at 6328 A have been measured for
      carbon disulfide, toluene, benzene, chloroform, carbon tetrachloride,
      cyclohexane, butanone, acetone, methanol, and water using an improved model of
      the low-angle laser light-scattering (LALLS) photometer. Small errors in some of
      the Rayleigh factors published using an earlier model of this instrument have
      been revealed. Depolarization ratios are measured by a new method involving
      detection of the full cone of forward scattered light.

PMID- 20134599
TI  - Beam deviation errors in ellipsometric measurements; an analysis.
AB  - The types of error produced by beam deviation in the optical elements of an
      ellipsometer are examined. It is shown that there are two types of error that may
      be significant-systematic errors due to a variation in the plane of incidence and
      in the angle of incidence at the specimen and errors due to the combined effects
      of beam displacement and nonuniformities in either the detector response or the
      optical properties of the specimen, the compensator, the polarizer, the analyzer,
      or the specimen cell. Analytic expressions for the variation in the plane of
      incidence and in the angle of incidence are given in terms of parameters that can
      be determined experimentally. A method by which these parameters can be measured
      is described. It is shown that the azimuthal variation in the angle of incidence
      produces fundamental errors in conventional zone averaging techniques because the
      values of psi and Delta are averaged at different angles of incidence in
      different zones. Methods of experimentally predetermining when such errors are
      likely to be significant are discussed, and a procedure that cancels most
      systematic errors due to beam deviation in each zone is described. The combined
      effects of beam deviation in the polarizer, the compensator, the cell windows,
      and the analyzer are considered in several commonly used configurations, and the
      configurations that minimize beam deviation errors are described.

PMID- 20134600
TI  - Application of a model for the inherent contrast conditions in full-form objects.
AB  - The concept has been developed of a simple model that is representative of the
      luminance and contrast conditions on full-form objects. A reasonably realistic
      approach is a sphere that is exposed to the irradiation from the entire sky, the
      sun, and the ground, taking into account the considerable variation of the
      luminance in the sky. Based, primarily, on measurements of the sky luminance in
      the Pikes Peak region of Colorado, calculations were made of the inherent surface
      contrast in such a model when it is viewed from any direction with fields of view
      of various sizes. Other calculations were concerned with the model object's
      contour contrast against its background and with its color. Representative
      results of these calculations are shown and discussed.

PMID- 20134601
TI  - Sensitive technique for measuring differences in reflectivity.
AB  - A new technique for measuring reflectivity differences between two samples is
      reported. An electrically driven tuning fork is used to place the two samples
      alternately in the beam of a reflectometer, and a lock-in amplifier is used for
      detection of the difference signal. Advantages of this system include short
      deadtime, vacuum operation, and extremely high Q. The sensitivity is such that
      changes in reflectivity of the order of 0.001% can be observed.

PMID- 20134602
TI  - Performance Characteristics of a 10-kW Industrial CO(2) Laser System.
AB  - Performance characteristics of an industrial high powered laser system are
      presented. These include laser gain and laser medium quality measurements that
      show that the laser system is capable of delivering a 15 kW, near diffraction
      limited beam to a focal point. A description of this laser system is also given.

PMID- 20134603
TI  - Quantum efficiency and instrumental polarization of an optical monochromator.
AB  - Experiences from a determination of the over-all quantum efficiency and
      instrumental polarization of an optical monochromator and detection system (near
      ultraviolet, visible, and near infrared), including application of imperfect
      polarizers, are discussed and related to atomic and electronic collision studies.

PMID- 20134605
TI  - Applied Optics Of optics and opticists.

PMID- 20134604
TI  - Performing optical measurements in solids under variable uniaxial stress and
      temperature: a system.
AB  - A modified version of a well-known apparatus is described, which is capable of
      delivering a compressive uniaxial stress beyond the range of stresses previously
      attained. With a simple rearrangement the same system may also be used to apply a
      tensile uniaxial stress. The apparatus can be readily used for optical
      measurements in solids under conditions of fixed or variable temperature in the
      range from 77 K to at least room temperature.

PMID- 20134606
TI  - Patents.
AB  - 3,784,791; 3,785,262; 3,785,265; 3,786,180; 3,786,238; 3,790,284; 3,792,915;
      3,794,406; 3,796,476; 3,796,494; 3,796,887; 3,797,907; 3,797,910; 3,797,922;
      3,799,653; 3,799,654; 3,800,149; 3,801,181; 3,801,188.

PMID- 20134607
TI  - Distributed Feedback GaAs Homojunction Injection Laser.

PMID- 20134608
TI  - Optical activities in industry.

PMID- 20134609
TI  - Light path steering with memory in as-s films.

PMID- 20134610
TI  - Unstable Optical Resonators: comment.

PMID- 20134611
TI  - Dye removal from holographic films.

PMID- 20134613
TI  - Laser Doppler interferometer: analysis.

PMID- 20134612
TI  - Optical Homogeneity of a Ultraviolet-Preionized CO(2) Laser Discharge.

PMID- 20134614
TI  - Rotary spark gap switching for high power dye lasers.

PMID- 20134615
TI  - Temperature Change of the Refractive Index of CVD ZnSe at 10.6 microm.

PMID- 20134617
TI  - Cold-Electron Temperature Measurements in ELMO by Excitation Rate Ratios of
      Vacuum Ultraviolet Transitions.

PMID- 20134616
TI  - Rapidly gated crossed-field photomultiplier.

PMID- 20134618
TI  - Reflective schmidt corrector.

PMID- 20134619
TI  - Influence of the quadratic magnetooptical effect on light propagation in garnet
      films.

PMID- 20134620
TI  - Holographic methods for painting diagnostics.
AB  - A holographic method for detecting detached regions between the priming layers
      and the underlying wood support in panel paintings is described. Experimental
      results obtained by the application of the method both on laboratory models and
      on an ancient Italian panel painting are presented. The great advantages that
      this technique can offer to the conservation and restoration of works of art are
      emphasized.

PMID- 20134621
TI  - Elimination of wavefront aberration of optical elements used in phase difference
      amplification.
AB  - Two holograms are used. A first hologram is recorded by the light that passes
      through the phase object with an ordinary off-axis holographic system. A second
      hologram is recorded by the light that passes through the deformed object and is
      diffracted by the first hologram and processed nonlinearly. Phase difference
      amplification is performed by the superposition of two higher harmonic waves from
      the second hologram. In a resultant interferogram of eight-fold phase difference
      amplification, phase change, due to only the deformation of the object, is
      amplified; and wavefront aberration, caused by poor quality of an optical system
      and by inhomogeneity of the object, is completely eliminated.

PMID- 20134622
TI  - Sandwich hologram interferometry: a new dimension in holographic comparison.
AB  - New methods are introduced that utilize interferometric comparison of images of
      diffusely reflecting objects from different hologram plates that are sandwiched
      together. To make the plate positions optically and mechanically identical during
      reconstruction and exposure, they are also exposed in sandwiches. If the two
      sandwiched hologram plates are separated by a small distance a new method of
      fringe evaluation can be used. Fringes caused by object tilt between two
      exposures can be eliminated by an analogous, but much larger, tilt of the
      sandwich hologram during reconstruction. Even the direction of tilt, forward or
      backward, is found this way.

PMID- 20134623
TI  - Camera testing by use of speckle patterns.
AB  - A beam of laser light enters the camera. The light diffusely reflected by the
      film re-emerges, and the speckle pattern formed at the plane of the lens
      diaphragm is observed. A traversing lens produces slight movements of the light
      spot at the film plane. If the camera is out of focus these cause bodily
      movements of the speckle pattern. As the focal position is approached the speckle
      size and rate of movement increase and finally give way to a random change of
      structure. The focal position can be estimated to within 0.1 or less of the
      Rayleigh limit. Using this it is possible to measure all the primary and
      secondary aberrations (other than distortion) of the camera, including any errors
      of film position.

PMID- 20134624
TI  - Holographic radial shear interferometer.
AB  - A new type of radial shear interferometer based on the imaging properties of
      Gabor zone plates is described. This interferometer is stable, easily
      constructed, and is a useful instrument in optical testing.

PMID- 20134625
TI  - Linear recording condition in multirecording telecine system.
AB  - Since the multirecording telecine system includes the negative photographic film
      as a component, it is a nonlinear system. In this paper, the distortions of the
      three electrical primary color signals generated by the film nonlinearity are
      analyzed and represented as the function of the film gamma gamma and recording
      level. The chromaticity errors of the reproduced image are calculated for various
      values of gamma and recording level k The condition where the color differences
      of all colors are less than 7.5 is defined as the linear recording condition. The
      regions of gamma and k to satisfy this linear recording condition are calculated.

PMID- 20134626
TI  - High density image-storage holograms by a random phase sampling method.
AB  - The random phase sampling method that has been proposed to make high quality and
      high storage density holograms capable of storing image information is described
      and discussed from the aspect of the quantitative characteristics of its
      reconstructed image. The method enables the uniform distribution of light energy
      over the hologram area made on the exact Fourier transformed plane. The details
      of the characteristics of the method are investigated, especially with respect to
      the luminance tone linearity, the signal-to-noise ratio, and the resolution to
      give good agreement with the results of a calculation. In the experiment,
      reconstructed images with high quality were obtained from holograms of 2-mm diam,
      which were made by 10(6) sampling and random phase shifting. By using the random
      phase sampling medthod, an image retrievel model system storing twenty kinds
      information was developed. This system holds promise of being used in various
      practical applications such as holographic ultramicrofilm system or a holographic
      videopackage system.

PMID- 20134627
TI  - Imaging Characteristics of the Itek PROM.
AB  - This paper discusses advances in the fabrication, operation, and performance of
      the Itek PROM (Pockels readout optical modulator). Devices of high optical
      quality have been made and evaluated. Measurements of MTF and sensitivity under
      various conditions are presented. Stored images can be enhanced in contrast by a
      change in device voltage and the same method used to suppress the zero order in
      Fraunhofer diffraction patterns of such images. The results of this technique are
      demonstrated.

PMID- 20134628
TI  - Image reproduction with interactive graphics.
AB  - Software application or development in optical image digital data processing
      requires a fast, good quality, yet inexpensive hard copy of processed images. To
      achieve this, a Cambo camera with an f 2.8/150-mm Xenotar lens in a Copal shutter
      having a Graflok back for 4 x 5 Polaroid type 57 pack-film has been interfaced to
      an existing Adage, AGT-30/Electro-Mechanical, EMR 6050 graphic computer system.
      Time-lapse photography in conjunction with a log to linear voltage transformation
      has resulted in an interactive system capable of producing a hard copy in 54 sec
      (Fig. 1). The interactive aspect of the system lies in a Tektronix 4002 graphic
      computer terminal and its associated hard copy unit (Fig. 2).

PMID- 20134629
TI  - Aplanatic two-mirror telescopes: a systematic study. 1: cassegrainian
      configuration.
AB  - A systematic performance analysis of aplanatic Cassegrainian telescopes has been
      accomplished by means of a ray trace program. The results indicate that the
      available field angle for a given geometric spot size is, to a very close
      approximation, a function of the relative back focal distance only. Image
      curvatures, as computed by third-order theory and by the ray trace program, were
      found to be in very close agreement. Image curvature is plotted as a function of
      the ray height ratio for a wide range of secondary magnification.

PMID- 20134630
TI  - Copying lens for microfilm photography.
AB  - A new lens design for precise copying exemplifies the success of the rms error
      function as a suitable criterion for the design of high resolution lenses. The
      design, a 145-mm f/4.0, gives 400-line/mm, high contrast,white-light visual
      resolution throughout a 30-mm flat image when used at 20:1 conjugates. On high
      resolution plates, a resolution of 320 lines/mm is obtained. The five-glass
      design has no vignetting of the marginal beams, presents no manufacturing
      problems, and gave full resolution when first assembled. The prescriptionwas
      found by the LASL 1972 Lens Design Program.

PMID- 20134631
TI  - Thermal blooming of rapidly slued laser beams.
AB  - Thermal blooming of laser beams propagating through the atmosphere has generally
      been treated for cases of small wind speed transverse to the beam. The present
      calculation examines the associated density changes for air moving through a beam
      at near sonic speeds. The problem is treated for the one-dimensional case only;
      an exact solution to the nonlinear hydrodynamic equations for the steady state is
      derived. The solution shows that, at near sonic speeds, the density changes grow
      drastically with Mach value, while agreeing with the previous results at low wind
      speeds. In the vicinity of Mach I, the solution becomes invalid, probably due to
      the nonexistence of a steady state. The effect of the density changes on the beam
      are not calculated here.

PMID- 20134632
TI  - Optical Coatings for High Energy ZnSe Laser Windows.
AB  - The development of surface finishing and coating technology at 10.6 microm for
      polycrystalline ZnSe laser windows is presented. Optical evaluation of the coated
      windows shows that the 10.6-microm absorption and reflection can be held to less
      than 0.1% per surface. Surface finishing procedures, theoretical coating designs,
      and recent experimental results for antireflection coatings for ZnSe are
      presented.

PMID- 20134633
TI  - High power nd:glass laser for fusion applications.
AB  - Experiments on laser-induced thermonuclear fusion require high brightness lasers
      capable of producing subnanosecond pulses with total energy content of several
      kilojoules. Of existing laser media, Nd:glass appears to be the best choice for
      meeting these criteria. In this paper we discuss the problems of designing a high
      power Nd:glass laser system. A detailed description of an operating two-beam
      system producing subnanosecond pulses with a maximum energy of 350 J per beam is
      presented, along with an extensive description of beam diagnostic techniques. A
      four beam version of this system became operational on 3 April 1974 and is now
      producing energies in excess of a kilojoule in subnanosecond pulses.

PMID- 20134634
TI  - Application of pressure scanning to the tuning of a high resolution dye laser.
AB  - Advantages of pressure scanning over other methods of tuning the wavelength of
      dye lasers are discussed. The construction of a pressure scanned high resolution
      dye laser is described. The laser has a scan range of more than 40 cm(-1) in its
      intermediate resolution mode, an improvement on the order of a hundredfold over
      previous methods of tuning. Preliminary tests have indicated a scan range of 4
      cm(-1) in the high resolution mode. As a demonstration of its applicability and
      versatility, the laser was used to xesolve the ground state splitting of the
      chromium isotopes in ruby.

PMID- 20134636
TI  - High resolution lenses for optical waveguides.
AB  - A mode index lens and a lens formed by a spherical depression in the substrate of
      the waveguide have opposite aberrations and can be combined in an element with
      considerably reduced aberrations. Only small differences in the mode index are
      required for the optimum combination.

PMID- 20134635
TI  - Prepulse enhancement of flashlamp pumped dye laser.
AB  - A simple technique has been developed that increases the power output of a
      conventional flashlamp pumped dye laser by typically one order of magnitude and,
      for some dyes, much more. This is achieved by igniting a low-energy prepulse
      discharge through the flashlamp just prior to firing the main flashlamp
      discharge.

PMID- 20134637
TI  - Passive cryogenic cooling of electrooptics with a heat pipe/radiator.
AB  - The current status of the heat pipe is discussed with particular emphasis on
      applications to cryogenic thermal control. The competitive nature of the passive
      heat pipe/radiator system is demonstrated through a comparative study with other
      candidate systems for a 1-yr mission. The mission involves cooling a spaceborne
      experiment to 100 K while it dissipates 10 W.

PMID- 20134638
TI  - Refractive index profile measurements of diffused optical waveguides.
AB  - Refractive index profiles resulting from the fabrication of optical waveguides by
      diffusion techniques are measured using a reflection interferometric technique.
      In Cd-diffused ZnSe waveguides, the index variations are found to be
      complementary error functions that closely follow the composition changes for
      deep (>5 microm) diffusions. Shallow (<5 microm) diffusions produce waveguides in
      which the index profile is a complementary error function that differs
      significantly from the composition profile. The relationship between composition
      and refractive index is determined for Cd compositions less than 10%. Refractive
      index profiles in commercially available diffused glass waveguides (SELFOC rod
      and fibers) are also described.

PMID- 20134639
TI  - Resonator theory for hollow waveguide lasers.
AB  - A numerical technique has been developed for analyzing the transverse modes of
      waveguide lasers with external mirrors. Propagation outside the guide is computed
      with the Fresnel-Kirchhoff diffraction integral and within the guide by
      decomposing the fields into the characteristic modes of the guide structure. The
      transverse modes of the entire waveguide-mirror system fall into a number of
      distinct classes: TE(0m), TM(0m), EH(1m), EH(2m), etc. For each class of modes,
      the, corresponding guide modes form a complete and orthogonal set and may be used
      as basis vectors to describe those modes. This reduces the mode analysis of the
      waveguide resonator to the diagonalization of a small (5 x 5 or 10 x 10) complex
      matrix. Guide losses, coupling losses, and mode shapes will be discussed for a
      number of interesting cases, with the Fresnel number of the waveguide ranging
      from 0.1 to 1.0 and with various values of mirror curvature and position. It will
      be shown that some vales of resonator parameters are particularly advantageous
      for achieving single mode operation.

PMID- 20134640
TI  - Marechal intensity criteria modified for gaussian beams.
AB  - The Marechal evaluation of the Strehl definition is reexamined for a Gaussian
      aperture where we have included the primary aberrations and all orders of
      spherical aberration. The result is particularly useful for evaluating the far
      field peak intensity degradation, due to aberrations, for a well-corrected
      optical system when the wavefront distortion at the exit pupil is known. Further,
      the resulting equations have the same form as Marechal's equations for a uniform
      beam with the exception of additional factors that are the consequence of the
      Gaussian beam. These factors approach unity as the Gaussian beam approaches a
      uniform beam. As a consequence, the effects of the Gaussian illumination are
      readily identified. It is also shown how various aberrations may be balanced
      against one another in order to obtain the best peak intensity in the presence of
      a truncated Gaussian beam.

PMID- 20134641
TI  - Optical antenna gain. 1: transmitting antennas.
AB  - The gain of centrally obscured optical transmitting antennas is analyzed in
      detail. The calculations, resulting in near- and far-field antenna gain patterns,
      assume a circular antenna illuminated by a laser operating in the TEM(00) mode. A
      simple polynomial equation is derived for matching the incident source
      distribution to a general antenna configuration for maximum on-axis gain. An
      interpretation of the resultant gain curves allows a number of auxiliary design
      curves to be drawn that display the losses in antenna gain due to pointing errors
      and the cone angle of the beam in the far field as a function of antenna aperture
      size and its central obscuration. The results are presented in a series of graphs
      that allow the rapid and accurate evaluation of the antenna gain which may then
      be substituted into the conventional range equation.

PMID- 20134642
TI  - Radiometric properties of isothermal, diffuse wall cavity sources.
AB  - Total radiant power emission from various diffuse wall cavity sources is
      calculated without approximation. In addition, a useful radiometric quantity, (o
      d), the fraction of blackbody power received by a distant viewer, is precisely
      defined and calculated. Extensive tabulation of numerical results and tutorial
      background are included. A new method, faster and more accurate than traditional
      quadrature methods, for the numerical solution of integral-equations is described
      in an appendix. Results are applied to the practical problems of cavity design
      and analysis.

PMID- 20134643
TI  - Influence of bottom depth and albedo on the diffuse reflectance of a flat
      homogeneous ocean.
AB  - The influence of the bottom albedo on the diffuse reflectance of a flat,
      homogeneous ocean is computed as a function of bottom depth and albedo for three
      oceanic scattering phase functions and several values of omega(0). The results
      show that the bottom can have a large effect on the reflectivity, especially for
      small optical depths. When combined with the observed optical properties of clear
      natural water, the calculations are shown to be in good agreement with the
      observed dependence of in-water nadir radiance spectra, with depth. The apparent
      independence of the reflectance on the mode of illumination observed earlier for
      the infinitely deep ocean is found to be invalid for a shallow ocean. The effect
      of departures of the bottom law of diffuse reflectance from Lambertian is
      investigated and shown to be considerable in some cases.

PMID- 20134644
TI  - Rayleigh, the unit for light radiance.
AB  - A 0.7% accurate formula is derived for the easy conversion of power spectral
      radiance L(lambda) in W cm(-2) sr(-1) microm(-1)to rayleigh spectral radiance
      R(lambda) in rayleigh/microm, R(lambda) = 2pilambdaL(lambda) x 10(13), where the
      wavelength lambda is in microm. The rationale for the rayleigh unit is discussed
      in terms of a photon rate factor and a solid angle factor. The latter is
      developed in terms of an equivalence theorem about optical receivers and extended
      sources, and the concept is extended to the computation of photon volume emission
      rates from altitude profiles of zenith radiance.

PMID- 20134645
TI  - Effect of Electron Deexcitation and Self-Absorption on the Intensity of the Hg
      2537-A Radiation from Hg + Ar Discharges (ac Fluorescent Lamps).
AB  - The intensity of the Hg 2573-A radiation from Hg + Ar discharges was measured as
      an independent function of mercury pressure (0.2-50 mTorr), ac current (50-2100
      mA) and tube radius (0.79 cm and 1.27 cm) at a constant Ar pressure of ~4 Torr.
      For various constant mercury pressures, the Hg 2537-A intensity initially rises
      linearly with increasing current, but then tends to bend over and approach an
      asymptotic limit. The nonlinear, asymptotic behavior is due to electron
      deexcitation of the Hg 6(3)P(1) state at the higher currents in the presence of
      Hg 2537-A self-absorption. The Hg 2537-A intensity was also measured as a
      function of mercury pressure at various constant currents. The intensity rises to
      a peak (which defines an optimum Hg pressure) and then decreases with further
      increase in mercury pressure due to the combination of self-absorption and
      electron deexcitation. For high ac currents, the optimum Hg pressure is
      independent of current but varies inversely with the tube diameter. All this
      behavior is relevant to the problem of obtaining high efficiency from fluorescent
      lamps at high powers.

PMID- 20134647
TI  - Bemporad's Airmass Function: Comment.

PMID- 20134646
TI  - Estimation of optical field mean intensities from photocount correlations.
AB  - An extremely simple procedure is given for estimating the mean intensity of each
      component of a twocomponent optical field from measurements of the number of
      photocounts recorded over counting intervals of T sec duration spaced tau sec
      apart. The only a priori knowledge required about each component is the
      functional form of the first- and second-order coherence functions and an order
      of magnitude estimate of their coherence times.

PMID- 20134648
TI  - Confocal paraboloids: some comments.

PMID- 20134649
TI  - Noise in fiber optics communications systems induced by ionizing radiation.

PMID- 20134651
TI  - Applied optics of optics and opticists.

PMID- 20134650
TI  - Field-widened michelson spectrometer with no moving parts: comments.

PMID- 20134652
TI  - Patents.
AB  - 3,619,021; 3,628,849; 3,644,014; 3,647,278; 3,663,089; 3,659,927; 3,661,441;
      3,661,442; 3,682,532; 3,675,986; 3,675,989; 3,713,721; 3,718,078; 3,718,751;
      3,719,415; 3,728,545; 3,729,253; 3,734,619; 3,783,295; 3,792,916; 3,793,518;
      3,795,803; 3,796,479; 3,797,911; 3,797,913; 3,798,366; 3,798,452; 3,800,156;
      3,801,185.

PMID- 20134653
TI  - Double pass laser amplifiers.

PMID- 20134654
TI  - Comparison Between Two Methods of SNR Measurement of Image Tubes.

PMID- 20134655
TI  - Analysis and experimental study of ruled half-tone screens: addendum.

PMID- 20134656
TI  - Characteristics of a photoresist hologram and its replica: errata.

PMID- 20134657
TI  - More on afocal parabolic reflectors.

PMID- 20134658
TI  - Still more on afocal parabolic reflectors.

PMID- 20134659
TI  - Limitations in using atmospheric models for laser transmission estimates.

PMID- 20134660
TI  - Pseudo Color Densitometer Analysis-the Apollo 17/Saturn V Exhaust Plume.
AB  - Spectra of the Apollo 17/Saturn V exhaust plume have been obtained in the uv
      (300ndash;400 nm), visible (400-650 nm), and ir (750-790 nm) regions. Analysis of
      these data with a pseudo color densitometer reveals (1) a standing wave pattern
      in the exhaust plume characterized by a wavelength of 9 m, (2) a region of
      intense continuum within 40 m of the exit plane which supports previous reports
      of a continuum blackbody source with a peak temperature near 2600 K, (3) a region
      of continuum emission beyond 40 m that is not blackbody, and (4) line emissions
      beyond 40 m attributed to the sodium D lines and potassium. It is suggested that
      an interference filter centered on the sodium D lines could be used on a high
      speed framing camera to study the turbulent structure of the plume in the
      nonblackbody region.

PMID- 20134661
TI  - Selective material x-ray imaging using spatial frequency multiplexing.
AB  - A method is presented of encoding the transmission at specific regions of the x
      ray energy spectrum onto a radiograph. A grating structure is placed in the x-ray
      beam that consists of alternate strips of material having different x-ray
      transmission spectra. The average spectral transmission of the two strips
      produces an image comparable to a conventional radiograph. The difference between
      the two transmission spectra produces an amplitude modulation of the grating
      pattern on the radiograph. When this grating pattern is decoded, through optical
      or scanning methods, it represents the transmission at the specific x-ray
      difference spectrum.

PMID- 20134662
TI  - Measurement of low level photodiode noise currents.
AB  - Graphs giving the unilluminated noise current of four different photodiodes under
      various bias conditions are presented. To make these measurements a system was
      developed with a noise sensitivity of less than 10(-5)A/Hz((1/2)). The
      preamplifier used is briefly described.

PMID- 20134663
TI  - Infrared reflectometry with a cavity-shaped pyroelectric detector.
AB  - A new type of reflectometer has been developed for measuring directional
      hemispherical spectral reflectances in the infrared region. The instrument is
      based upon a cavity-shaped pyroelectric detector that itself collects the
      radiation reflected by the test sample, thereby obviating the need for an
      intermediate collector such as an integrating sphere or concave mirror. This
      detector is made from an electrically polarized plastic film of polyvinyl
      fluoride, coated with gold-black on its inner surface and backed with brass him
      on its outer surface in order to provide mechanical strength. The reflectometer
      has been used with Fourier spectrometer to measure spectral reflectances over the
      wavelength range 5-30 microm.

PMID- 20134664
TI  - Highly reflecting stable white paint for the detection of ultraviolet and visible
      radiations.
AB  - The use of polyvinyl alcohol polymer as a binder for barium sulfate does not
      allow the intrinsically high reflectance of barium sulfate in the 200-300-nm
      range to be optimally employed. In an effort to better utilize this property,
      totally inorganic coating systems are described. Potassium sulfate turns out to
      be the preferred binder for reflectance enhancement. Compositions, formulating
      procedures, and application techniques are included. For completeness, absolute
      and relative reflectance data are included for intrasystem and intersystem
      comparisons.

PMID- 20134665
TI  - Performance tests for automatic ellipsometers.
AB  - Methods to determine quantitatively the dynamic response of automatic
      ellipsometers to variations in the optical properties of a specimen have been
      developed and are illustrated by data from a newly built ellipsometer. The
      quantities determined include slew rate, frequency response, accuracy, and
      resolution. The methods are based on the use of rotating mirrors for the
      generation of well-defined, fast optical changes in the reflecting surface.

PMID- 20134666
TI  - Determination of polarization in optical instruments and its metrological
      implications.
AB  - One of the working programs of the CIE Technical Committee on Photometric and
      Radiometric Characteristics of Materials (CIE, TC-2.3) deals with polarization
      problems. The subcommittee working on this program is concerned with those topics
      of polarization that deal with the photometric and radiometric characteristics,
      particularly with instrumental polarization, which causes unpredictable variation
      in light transmitted, reflected, absorbed, or emitted-quantities all dependent on
      the sample type and measurement configurations. We present in this paper in
      summary form the results of some of the work that was reported at the Committee
      Meeting in London, England, in July 1973.

PMID- 20134667
TI  - Hadamard-transform spectrometry of the atmospheres of Earth and jupiter.
AB  - A Hadamard-transform spectrometer has been used to obtain a spectrum of Jupiter
      from 880 cm(-1) to 770cm(-1) Three ammonia absorption features stand out at 870
      cm(-1), 851 cm(-1), and 833 cm(-1). The general shape of the spectrum implies an
      atmosphere with a monotonically decreasing temperature profile up to the 125 K
      level. In addition, transmission profiles of the earth's atmosphere were taken
      between 16 microm and 25 microm for five consecutive nights under varying amounts
      of atmospheric water and air mass. There are many saturated lines, but nightly
      variations are constant and agree well with a theoretical profile. These results
      show that the Hadamard-transform technique is a useful method for obtaining
      astronomical spectra.

PMID- 20134668
TI  - Improving the accuracy of jarrell-ash microphotometers.
AB  - A modification to a Jarrell-Ash model 23-100 recording microphotometer used to
      read spectroscopic plates is described. The modification allows the motion of the
      plate to drive incrementally a stepper motor chart recorder. The modification
      uses inexpensive off-the-shelf components and was installed in the field. The
      plate reading accuracy of the instrument was improved by a factor of 2-5, and
      problems associated with occasional plate drive slippage were eliminated.

PMID- 20134669
TI  - Ratio Method of Fourier Spectrometry: an mprovement.
AB  - If the two detectors of a ratioing dual-beam interferometer do not have identical
      spectral responses, the sum of the two signals will have undesirable residual
      fringes; a spectrum derived from the ratio of the difference of the two signals
      to the sum will be distorted. Our technique allows removal of these fringes with
      only a small effect on any other modulation (such as source intensity modulation)
      in the sum signal. We find the average ratio of the sum fringe spectrum to the
      difference spectrum. Multiplying this average ratio by the spectrum from an
      arbitrary difference interferogram predicts the expected fringes in the sum
      signal, which can then be removed.

PMID- 20134670
TI  - Coherent optical noise suppression device.
AB  - In optical data processing the quality of the output image is usually degraded by
      diffraction noise generated by the optical components of the system. The
      suitability of previously suggested techniques to a dc spatial filtering
      processor is discussed. A new system is proposed that overcomes the problems of
      the previous noise suppression techniques. Experimental results of the new system
      are presented along with a determination of the resolution of the system. The
      errors and limits of the new coherent noise suppression system are discussed.

PMID- 20134671
TI  - Contrast enhancement of light emitting diode displays.
AB  - This paper describes a technique for calculating the resultant contrast of
      displays incorporating various filters or filter combinations. In particular,
      contrast of such displays employing red or green light emitting diodes (LED's) as
      the active elements is tabulated. The results indicate that adequate contrast
      enhancement of red LED's in high light level environments is usually achieved
      using neutral density or bandpass filters with antireflective coatings. Green
      LED'S must be designed to have a high degree of specular reflectance so that a
      circular polarizer may be employed in order to achieve similar results. A
      discussion of required filter bandwidth to accommodate shifts in peak spectral
      output of LED'S due to manufacturer's tolerances and temperature effects is also
      included.

PMID- 20134672
TI  - Precision electronically controlled optical printer for 3-d stereoorthophoto
      mapping.
AB  - A precision optical printer is described for producing stereoorthophoto maps from
      aerial stereo photos, complete with the rectified image of the terrain, contours,
      symbols, and annotation. The printer forms part of the stereoorthophoto system
      that was conceived and is currently under development at the National Research
      Council of Canada. Stereoorthophotos bring to potential users for the first time
      a complete, precise, accurately scaled, stable stereo terrain image that can be
      viewed with simple equipment. The digital electronic techniques used to realize
      the precision control and versatility required in such an optical device are
      described generally.

PMID- 20134673
TI  - Holographic interferometric microscopy of polymer crystallization.
AB  - The application of holographic interference microscopy to the study of polymer
      crystallization from the melt is described. The two holographic interferometric
      techniques that have been found to be most suitable in the study of polymer
      systems utilize (1) the double exposure hologram and (2) the simultaneous
      wavefront reconstruction from two separate holograms. Results indicate that both
      methods are essential. The initial evaluation of the origin and magnitude of
      optical path changes requires the application of both interferometric approaches.
      This study establishes the feasibility of holographic interferometric methods for
      the study of secondary crystallization in polymer systems and for the
      characterization of morphological boundaries in polymer melts.

PMID- 20134674
TI  - Television based fourier holographic system.
AB  - A system for recording Fourier transform holograms on a television camera for use
      with an existing realtime reconstruction device is described. Measurements of the
      system's visibility, associated efficiency measurements, and a general procedure
      for determining the system's optimum operating point are presented. Initial off
      line reconstructions and a comparison of various optical synthesis systems for
      television based Fourier transform holograms are included.

PMID- 20134675
TI  - Magnitude-coupled phase quantization.
AB  - A method is described for minimizing Fourier-domain phase-quantization noise in
      the image reconstructed from a computer-generated hologram. This method uses
      manipulation of the hologram magnitude to counteract the deleterious effects of
      phase quantization.

PMID- 20134676
TI  - Multiple-Sine-Slit Microdensitometer and MTF Evaluation for High Resolution
      Emulsions. 1: Theory and Mode of Operation.
AB  - The Multiple-Sine-Slit Microdensitometer (MSSM) measures transmittance modulation
      by scanning the sample with a sinusoidal irradiance distribution generated by
      laser two-beam interference. The theory of the instrument is derived both from
      conventional microdensitometry and from treating the sample as a complex valued
      grating that diffracts two impinging coherent fields. The instrument has a
      constant MTF of 0.5; its principle disregards any phase modulations in the
      sample; and its large measuring area improves signal-to-noise ratio by 1-2 orders
      of magnitude. These are necessary qualifications for determining the MTF of
      recording materials of very high resolution. With a He-Ne laser, the range of the
      MSSM spans from 4 c/mm to 1500 c/mm. The practical implementations of the
      evaluation of film MTF's with this system are described.

PMID- 20134677
TI  - Multiple-Sine-Slit Microdensitometer and MTF Evaluation for High Resolution
      Emulsions. 2: MTF Data and Other Recording Parameters of High Resolution
      Emulsions for Holography.
AB  - By means of the Multiple-Sine-Slit Microdensitometer (MSSM), MTF's up to 1500
      c/mm have been evaluated for five photographic plates for holography, Agfa
      Gevaert Scientia 10E75, 8E75, 8E75B, and Kodak 649-F and Type 120-02. For
      comparison, an as-if-MTF has also been derived from diffraction efficiency
      measurements. In addition sensitivity at lambda = 633 nm, the macroscopic
      characteristic tau(A) vs logE and alpha(2)(E), and scattered-flux data are
      reported for these five plates.

PMID- 20134678
TI  - The laser lightning rod system: thunderstorm domestication.
AB  - An unusual application of the laser, namely protection of life and property from
      lightning, is described. The device relies on multiphoton ionization in mode
      locked beams, rather than on collisional (avalanche) electron production.
      Feasibility is demonstrated numerically, and relevant principles explained. A
      method of mobile deployment is mentioned, by which economic (as opposed to
      scientific) feasibility might be achieved.

PMID- 20134679
TI  - Ultrasensitive detection of cs vapor by intracavity laser quenching.
AB  - Intracavity laser quenching has been used to detect 9 x 10(7) atoms of Cs vapor.
      An enhancement factor of about 2000 over the sensitivity for single-pass
      detection is observed. Known techniques should make it possible to increase the
      sensitivity level to near 10(6) atoms.

PMID- 20134680
TI  - Flashlamp discharge and laser efficiency.
AB  - This paper presents an improvement in the method of calculating flashlamp
      performance and indicates how this can be used to evaluate the effect of
      flashlamp related system parameter changes on the efficiency of a solid state
      laser using such a flashlamp as a pump. It is shown that, in addition to being
      functions of the alpha and beta constants in the well-known theory of Markiewicz,
      Emmett, and Holzrichter, the normalized peak current and pulse width are also
      functions of the input energy. Furthermore, the product of peak current and pulse
      width is indicated to be the most significant factor relating lamp input and
      output. Finally, a curve is given for the fluorescence pumping efficiency and
      scaling of laser input-output levels is discussed.

PMID- 20134681
TI  - Faraday Rotation Optical Isolator for 10.6-microm Radiation.
AB  - Measurements that have been performed indicate that hot-pressed ferromagnetic
      CdCr(2)S(4) would be a useful Faraday optical isolator material for laser systems
      at 10.6 microm. A large-aperture, liquid-nitrogen-cooled isolator, requiring
      modest magnetic fields with material of optimum thickness, would provide
      isolation in excess of 30 dB with insertion loss due to optical absorption in the
      active element of less than 3 dB. Consideration of its figure of merit indicates
      that hot-pressed CdCr(2)S(4) could be used as an isolator at 1.06 microm,
      introducing less than 2 dB insertion loss due to optical absorption at that
      wavelength.

PMID- 20134682
TI  - Lasing characteristics of seventeen visible-wavelength dyes using a coaxial
      flashlamp-pumped laser.
AB  - The performance and tuning characteristic of organic dye lasers were measured
      using commercially available coaxial flashlamps as the pumping source. Tuning by
      a diffraction grating permitted continuous coverage of the 4200-7500-A region at
      up to 0.6% tuned output energy efficiency. Preliminary results with a 600-J Marx
      Bank coaxial laser at 4500 A show 1% efficiency and single-pass unsaturated gain
      greater than 20 at 4500 A.

PMID- 20134683
TI  - Multiple-selected-line unstable resonator.
AB  - A new type of unstable resonator has been developed that permits multiple
      selected-line operation. Selected-line operation is obtained with a diffraction
      grating that is oriented at an angle that is different from the Littrow angle.
      Secondary feedback mirrors at the appropriate angles provide an independent
      threeelement cavity for each wavelength selected. The off-Littrow configuration
      is less efficient than a singleline cavity at the Littrow angle because there are
      secondary zero-order beams at each wavelength as well as a primary zero-order
      beam at all selected wavelengths. In the limit of a high gain this loss in
      efficiency is shown to be significantly reduced. Two types of multiple-selected
      line unstable resonators are considered: an edge-coupled design, which produces
      an annular beam with a 45 degrees output coupling mirror, and a continuously
      coupled design, which uses the primary zero-order beam as output. Experiments
      have been carried out with a multiple-selected-line unstable resonator on a cw HF
      laser. Selected-line operation was obtained on the P(2) (5) and P(1) (6) HF
      transitions in a continuously coupled design.

PMID- 20134684
TI  - Direct application of the fast fourier transform to open resonator calculations.
AB  - It is shown how fast Fourier transform techniques can be used to efficiently,
      numerically evaluate (convolution) integrals of the form often encountered in
      open resonator eigenmode calculations.

PMID- 20134685
TI  - Nonoxide chalcogenide glass films for integrated optics.
AB  - We report the waveguiding properties of sputtered films of three chalcogenide
      glasses: As(2)S(3), Ge(28)Sb(l2)Se(60), and Ge(33)As(l2)Se(55), at 1.064microm.
      Propagation losses of less than 1 dB/cm have been measured for As(2)S(3) films.
      Delineated guides, as well as films, have been made and studied.

PMID- 20134686
TI  - Diffusion kinetics and optical waveguiding properties of outdiffused layers in
      lithium niobate and lithium tantalate.
AB  - Increases in the extraordinary refractive index sufficient to produce single and
      multimode optical waveguides have been produced by the outdiffusion of lithium
      oxide from the surfaces of lithium niobate and lithium tantalate crystals. The
      outdiffusion kinetics have been studied in detail by optical interferometry. The
      data fit a diffusion model for which the vaporizing surface flux is constant with
      time. For lithium niobate, the activation energy for diffusion is 68 +/- 1.2
      kcal/mol and does not vary with orientation. However the gradient of refractive
      index change at the surface is larger for diffusion normal to the c-axis than
      parallel to the c-axis. Activation energies for vaporization of 71 kcal/mol and
      59 kcal/mol were calculated from the model for diffusion perpendicular and
      parallel to the c-axis, respectively. The evaporation coefficient, alpha, was
      estimated to be less than 10(-4) with alpha perpendicular/alpha || approximately
      3 so vaporization is surface reaction limited. For lithium tantalate, the
      activation energy for diffusion is 51 +/- 6 kcal/mol and also does not vary with
      orientation. The activation energy for vaporization, Q(upsilon), is approximately
      63 kcal/mol and, within experimental error, is quite similar to that for lithium
      niobate. These values of Q(upsilon) indicate that the major vaporization species
      are probably lithium ions and oxygen ions. The characteristics of graded index
      waveguides are discussed and compared with those of slab guides. It is shown that
      in many respects the behavior of the two types is equivalent. We have produced a
      single-mode guide in lithium niobate with an effective thickness of 12 microm.
      Effective thicknesses as small as 6 microm are possible in lithium tantalate.

PMID- 20134687
TI  - Guidance of surface waves by multilayer coatings.
AB  - A periodic sequence of layers with alternately high and low refractive indices
      can guide loosely bound surface waves parallel to the layers. Most of the power
      flows in free space, and, thus, the losses may be considerably smaller than the
      bulk losses of the dielectric materials used. Possible applications are briefly
      discussed.

PMID- 20134688
TI  - Small particle signal characteristics of a dual-scatter laser velocimeter.
AB  - An analysis of the light intensity distribution at the crossover of two laser
      beams and its significance on the laser velocimeter is presented. The analysis is
      used to predict signal amplitude vs position of a single particle and to define
      the probe volume of the system.

PMID- 20134689
TI  - Integrated laser/radar satellite ranging and tracking system.
AB  - A laser satellite ranging system that is mounted upon and integrated with a
      microwave tracking radar is reported. The 1-pulse sec/ruby laser transmitter is
      attached directly to the radar's elevation axis and radiates through a new
      opening in the radar's parabolic dish. The laser photomultiplier tube receiver
      utilizes the radar's existing 20-cm diam f11 boresight telescope and observes
      through a similar symmetrically located opening in the dish. The laser system
      possesses separate ranging system electronics but shares the radar's timing,
      computer, and data handling[equation]recording systems. The basic concept of the
      laser[equation]radar is outlined together with a listing of the numerous
      advantages over present singular laser rangefinding systems. The developmental
      laser hardware is described along with preliminary rangefinding results and
      expectations. The prototype system was assembled to investigate the feasibility
      of such systems and aid in the development of detailed specifications for an
      operational system. Both the feasibility and desirability of such systems
      integrations have been adequately demonstrated.

PMID- 20134690
TI  - Transmission characteristics of three corning multimode optical fibers.
AB  - The loss spectra, refractive-index profiles, numerical apertures, and pulse
      dispersion characteristics of three multimode optical fibers made by Corning
      Glass Works have been measured at Bell Laboratories. The lowest transmission
      loss, 4.3-6.8 dB/km, was observed at 1.06-microm wavelength; in the 0.8-0.9
      microm spectral region the losses ranged from 6.6 dB/km to 11.6 dB/km. The
      numerical apertures of the fibers, designated as Nos. 1, 2, and 3, were
      calculated from the measured refractive-index differences to be 0.133, 0.157, and
      0.121, respectively. Pulse dispersion due to multimode effects in fiber No. 1 (1
      km long) was 8.4 nsec at 0.9-microm wavelength; the values were 6.0 nsec for
      fiber No. 2 (0.363 km long) and 2.6 nsec for fiber No. 3 (0.290Km).

PMID- 20134691
TI  - Viewing refractive-index profiles and small-scale inhomogeneities in glass
      optical fibers: some techniques.
AB  - Methods which have proved to be useful for measuring core-cladding refractive
      index differences, for approximating refractive-index profiles, and for viewing
      various inhomogeneities in solid multimode optical fibers are described. Optical,
      transmission-interference, and scanning-electron-beam microscopy have been used,
      and the illustrations include examples of photomicrographs made by each of these
      techniques.

PMID- 20134692
TI  - Analysis of scattering from fiber waveguides with irregular core surfaces.
AB  - The scattering from clad fiber optical waveguides that have cores whose surfaces
      are perturbed in various ways is calculated with the induced dipole method. Such
      scattering is of interest because it can couple the guided modes of a multimode
      waveguide, thereby reducing the temporal dispersion. The five surface deviations
      considered are a rectangular radial step, a sinusoidal perturbation of the
      radius, a sinusoidal meander of the core, a deviation where the core alternates
      periodically along the core axis between a y-extended elipse and a z-extended
      elipse (x is the core axis), and a helical meander of the core axis.

PMID- 20134693
TI  - Surface electromagnetic waves on metals and polar insulators: some comments.
AB  - The important parameters governing the propagation of surface electromagnetic
      waves (SEW) on metals or polar insulators have been theoretically investigated.
      General approximations for the propagation distance, decay distance, and
      penetration depth are presented in summary tables. It is found that the
      propagation distance of SEW can be used to study overlayer materials on metals,
      that the penetration depth of SEW fields into a metal is governed by the
      classical skin depth at low frequencies and by the plasma frequency in the
      visible wavelength region, that surface phonons can propagate over a centimeter
      on PbS, PbTe, and ferroelectrics, and that the propagation distances of SEW
      increase with decreasing temperature.

PMID- 20134694
TI  - Pressure and stress dependence of the refractive index of transparent crystals.
AB  - The pressure derivative of the refractive index (dn/dP) and the elastooptic
      constants (P(ij)) in the transparent frequency regime of semiconducting and ionic
      crystals are investigated theoretically. The electronic contribution to dn/dP of
      semiconductors is obtained by carrying out pseudopotential calculations of the
      band structure as a function of hydrostatic pressure, and the results compared
      with experiment. The lattice contribution to dn/dP is obtained by relating dn/dP
      to changes in the effective ionic charge and the phonon spectrum as functions of
      pressure. As for the P(ij), we perform a detailed application of the theory of
      Humphreys and Maradudin to calculate these for a variety of cubic crystals as
      functions of frequency in the transparent regime. The parameters required in the
      calculation are determined from improved prescriptions, which relate various
      microscopic functions to experimental data on the pressure dependence of phonon
      frequencies. The theoretical results are checked employing a relatio between
      dn/dP and the P(ij). Overall, one finds that frequency dispersion is most
      important for the ionic materials and is generally negligible for the more highly
      covalent materials.

PMID- 20134695
TI  - Optical antenna gain. 2: receiving antennas.
AB  - Expressions are derived for the gain of a centrally obscured, circular optical
      antenna when used as the collecting and focusing optics in a laser receiver which
      include losses due to (1) blockage of the incoming light by the central
      obscuration, (2) the spillover of energy at the detector, and (3) the effect of
      local oscillator distribution in the case of heterodyne or homodyne detection.
      Numerical results are presented for direct detection and for three types of local
      oscillator distributions (uniform, Gaussian, and matched) in the case of
      heterodyne or homodyne detection. The results are presented in several graphs
      that allow the rapid evaluation of receiver gain for an arbitrary set of
      telescope and detector parameters. It is found that, for uniform illumination by
      the LO, the optimum SNR is obtained when the detector radius is approximately
      0.74 times the Airy disk radius. The use of an optimized Gaussian (spot size =
      0.46 times the Airy disk radius) improves the receiver gain by less than 1 dB.
      Theuse results are insensitive to the size of the central obscuration.

PMID- 20134696
TI  - Systematic study of aplanatic two-mirror telescopes. 2: the gregorian
      configuration.
AB  - A systematic performance analysis of aplanatic Gregorian type telescopes has been
      carried out by means of a ray trace program. A comparison of the results with
      those of the first part of this article [C. L. Wyman and D. Korsch, Appl. Opt.
      13, 2064 (1974)] for aplanatic Cassegrains shows that the dependence of the
      performance on the system parameters is more complex for the Gregorian. Plots of
      the image curvatures as a function of the ray height ratio are shown for several
      secondary magnifications and a system focal length of 1000 cm.

PMID- 20134697
TI  - Influence of clouds, haze, and smog on the middle ultraviolet reaching the
      ground.
AB  - We extend the multiple scattering formalism of Shettle and Green using a turbid
      atmosphere of uniform horizontal layers with vertical nonhomogeneities by
      introducing uniform cloud, haze, and smog layers. Our solution follows the
      rigorous equations of Chandrasekhar. The fact that it is capable of handling a
      cloud layer of large optical thickness with minimal subdivision of that layer
      permits a fast computer solution. A formalism for treating a fractional cloud
      layer is presented, and this allows the interesting possibility of an increase in
      the global flux over the clear-sky case that was not allowed by the uniform
      layers. The uv spectral and dose results are then compared with existing
      experimental data, and averaged effects are presented and parameterized.

PMID- 20134698
TI  - Dustsonde and lidar measurements of stratospheric aerosols: a comparison.
AB  - On two nights in mid-September 1972, comparative measurements of stratospheric
      aerosol profiles, utilizing backscattered ruby laser light and direct in situ
      sampling were conducted over Laramie, Wyoming. The lidar backscattering and the
      particle number density profiles correlated well when the measured atmospheric
      molecular density profile was used to calculate the Rayleigh profile used in the
      lidar data reduction. The backscattered signal at 20 km was approximately 18%
      above Rayleigh and corresponded to a measured concentration of about one particle
      per cm(3) with diameters greater than 0.30 microm. Based on these initial
      comparative experiments, the ground-based lidar coupled with temperature
      soundings appears to be a possible method for determining the relative aerosol
      profile under present stratospheric loading conditions.

PMID- 20134699
TI  - Ocean color spectrum calculations.
AB  - There is obvious value in developing the means for measuring a number of
      subsurface oceanographic parameters using remotely sensed ocean color data. The
      first step in this effort should be the development of adequate theoretical
      models relating the desired oceanographic parameters to the upwelling radiances
      to be observed. A portion of a contributory theoretical model can be described by
      a modified single scattering approach based on a simple treatment of multiple
      scattering. The resulting quasisingle scattering model can be used to predict the
      upwelling distribution of spectral radiance emerging from the sea. The shape of
      the radiance spectrum predicted by this model for clear ocean water shows
      encouraging agreement with measurements made at the edge of the Sargasso Sea off
      Cape Hatteras.

PMID- 20134700
TI  - Absorber for solar power.
AB  - A simple, economical absorber utilizing a new principle of operation to achieve
      very low reradiation losses while generating temperatures limited by material
      properties of quartz is described. Its performance is analyzed and indicates
      approximately 90% thermal efficiency and 73% conversion efficiency for an earth
      based unit with moderately concentrated (~tenfold) sunlight incident. It is
      consequently compatible with the most economic of concentrator mirrors (stamped)
      or mirrors deployable in space. Space applications are particularly attractive,
      as temperatures significantly below 300 K are possible and permit even higher
      conversion efficiency.

PMID- 20134701
TI  - Alignment technique for unstable resonators.

PMID- 20134702
TI  - International communication: fifth holography school, novosibirsk, 29 january-3
      february 1973.

PMID- 20134703
TI  - Space Spangs-an Error.

PMID- 20134704
TI  - Patents.
AB  - 3,653,738; 3,661,065; 3,685,883; 3,694,055; 3,700,308; 3,702,214; 3,704,934;
      3,704,997; 3,783,403; 3,783,404; 3,783,406; 3,783,407; 3,792,918; 3,793,595;
      3,794,431; 3,800,243; 3,801,928; 3,794,835; 3,798,568; 3,798,569; 3,798,570.

PMID- 20134705
TI  - Optical activities in industry.

PMID- 20134706
TI  - GaAs Laser Diode Pumped Nd:YAG Laser.

PMID- 20134708
TI  - Modified ray tracing in a dielectric rod.

PMID- 20134707
TI  - Parylene C films for optical waveguides.

PMID- 20134709
TI  - Dispersion minimization in dielectric waveguides: comment.

PMID- 20134710
TI  - Signal processing for a signal with poisson noise: comments.

PMID- 20134711
TI  - Signal Processing for a Signal with Poisson Noise: Author's Reply to Comments.

PMID- 20134712
TI  - Light modulation with multilayer thin films.

PMID- 20134713
TI  - Thin film infrared channel spectra.

PMID- 20134715
TI  - Quadruple-exposure technique in stroboscopic holographic interferometry.

PMID- 20134714
TI  - Information content in remote sensing: comments.

PMID- 20134716
TI  - Convergence of a spectrum shaping algorithm.

PMID- 20134717
TI  - Submillisecond development of thermoplastic recordings.

PMID- 20134718
TI  - Real-time holographic motion picture camera capable of recording front surface
      detail from a random velocity vector: comments.

PMID- 20134719
TI  - Unit Color-Difference Figures Derived from the Proposed CIE 1976 L a b Space.

PMID- 20134720
TI  - Multistep hindle test.

PMID- 20134721
TI  - Sea Echo Measurements Made with 1.06-microm Laser Radiation.

PMID- 20134722
TI  - Simple Variable-Angle ATR Spectrophotometer Accessory.

PMID- 20134723
TI  - Dynamics of human teeth in function by means of double pulsed holography; an
      experimental investigation.
AB  - Investigation in vivo of small deformation and mobility processes in the
      masticatory system of man has been until now a very intricate problem. Mechanical
      as well as noncontact methods have been utilized earlier in order to record the
      mobility pattern of teeth and prosthodontic appliances. In this paper holographic
      interferometry will be presented as a solution of some odontological measurement
      problems. The method was first tested in a simulator arrangement and then used in
      a number of clinical experiments. A special, totally reflecting paint was used
      for surface preparation prior to holography. A Q-switched double-pulsed ruby
      laser was combined with an electronic subminiature force sensor for pulse
      triggering, which was actuated by the masticatory force of the patient. Force
      increases and pulse positions were registered synchronously on the screen of an
      oscilloscope. The applied force exerted by the patient's masticatory muscles
      could thus be defined according to its point of application, direction,
      amplitude, and duration. The corresponding surface deformation was evaluated by
      means of a synchronized, double-exposed hologram. Conclusions could be drawn
      regarding the relative and absolute mobility of the teeth and related structures
      of the holographed jaw section.

PMID- 20134724
TI  - Holographic ruby laser with long coherence and precise timing.
AB  - In this paper we report the development of a holographic ruby laser with a fringe
      free coherence length of over 1 m. The laser is electrooptically Q-switched for
      precise timing or for double-pulse operation. Oscillation is rigorously limited
      to a single axial mode with both a three-surface resonant reflector and a flowing
      dye solution. Incorporation of the dye into the cavity decreases the energy
      output by ~50%, but forces the laser to produce reliable, fringe-free holograms
      while relaxing the requirements on the oscillator. The oscillator's output of 12
      15 mJ was increased to about 0.8 J with two 15-cm (6-in.) amplifier stages.

PMID- 20134725
TI  - Minimization of the prime power consumption of a coupling-modulated gas laser
      transmitter.
AB  - The present article addresses itself to the prime power requirements of a
      coupling-modulated gas laser transmitter. The latter consists of a gas discharge
      tube and electrooptic modulator inside a laser resonator. In performing the
      calculations, the laser discharge length and the modulator voltage are
      simultaneously varied so that the transmitted power remains constant. In this
      way, tradeoffs can be made between the prime power supplied individually to the
      discharge tube and to the modulator driver to obtain a transmitter configuration
      that minimizes the total prime power consumption. An analytical expression is
      derived that describes the effects of information bandwidth and transmitter
      output power on the prime power requirements. Specific numerical results are
      obtained for a CO(2) laser transmitter based on presently available experimental
      data.

PMID- 20134726
TI  - Instrumental methods for air and water measurements and monitoring program,
      National Bureau of Standards, 14 Dec 1974.

PMID- 20134727
TI  - Stimulated emission from nuclei.
AB  - The feasibility of obtaining stimulated emission of both zero and finite mass
      particles from nuclei is considered, and the limitations imposed on the relevant
      nuclear parameters determined.

PMID- 20134728
TI  - Laser isotope separation using two-photon selective excitation; its quantum
      efficiency and separation factor.
AB  - Application of two-photon selective excitation to isotope separation with high
      power, high resolution tunable lasers is discussed. A simple kinetic model is
      given to determine quantum efficiency and separation factor in terms of laser
      powers and relaxation constants. A numerical example is used to demonstrate the
      feasibility of the scheme. Results indicate that a high quantum yield is
      obtainable with the optical technique.

PMID- 20134729
TI  - Optical quality of pulsed electron-beam sustained lasers.
AB  - The optical quality of a pulsed atmospheric CO(2) electric laser is investigated.
      The density disturbances in the optical cavity are caused by edge waves
      originating at the anode and cathode. Volumetric heating effects associated with
      a nonuniform electric discharge are shown to be negligible. The disturbance
      propagating from the cathode results from a discontinuity in the spatial heating
      and the cathode fall. The wave emanating from the anode is associated with the
      presence of a solid surface that prevents the gas from expanding. As a result,
      lasers have to be designed with pulse durations much less than the acoustic
      transit time across the cavity.

PMID- 20134730
TI  - Loss measurements in optical fibers. 1: sensitivity limit of bolometric
      techniques.
AB  - A new technique for measuring the attenuation of light in clad fibers is
      discussed. The basic approach is to measure the temperature rise produced in the
      fiber by the absorption of the light. Calculations indicate that the theoretical
      limit of sensitivity, which should be approachable with a relatively simple
      experimental configuration, is a loss of about 2.5 x 10(-7)/cm with 1 mW of light
      power and a 1-cm long sample. The theoretical sensitivity limit should improve
      with the square root of the sample length. A variation of the basic approach,
      which may make it possible to monitor attenuation in fibers as they are being
      drawn, is also discussed.

PMID- 20134731
TI  - Loss measurements in optical fibers. 2: bolometric measuring instrumentation.
AB  - This paper describes two approaches to measuring transmission losses in optical
      fibers by the thermal-rise technique. Rapid and convenient loss determinations
      can be made on short (~10-cm) lengths of fibers. Values of loss as low as ~10(-7)
      cm(-1) (0.043 dB/km) can be measured with transmitted light power of ~100mW.

PMID- 20134732
TI  - Lineshape measurement for coupling to waveguide modes in the prism-film coupler.
AB  - Coupling to optical waveguide modes was investigated by depositing two thin film
      layers on the hypotenuse of a rutile prism. Coupling efficiency was determined as
      a function of input beam angle for the three lowest order TE and TM modes. The
      coupling lineshape was found to agree with the predictions of a lossless, ray
      optics analysis for all but the lowest order TM modes. This result is explained
      in terms of the relative effects of loss on the coupling efficiencies of the
      various modes.

PMID- 20134733
TI  - Single-crystal electrooptic thin-film waveguide modulators for infrared laser
      systems.
AB  - Wideband, low power electrooptic modulators of optical waveguide structure have
      been developed for infrared laser applications. They allow a reduction in driver
      power of two orders of magnitude below that of conventional devices. The
      modulators are composed of very thin layers of single-crystal GaAs, bounded on
      both sides by evaporated films of lower refractive index material: CdTe or
      As(2)S(3). Minimum propagation loss, measured at 10.6 microm, was less than 1
      dB/cm for TE modes and less than 5 dB/cm for TM modes. A 20-pF modulator
      exhibited a pulse response rise time of 3 nsec and showed useful frequency
      response to beyond 200 MHz. The basic capability for advanced design modulators
      of this type to operate at 10 microm with driver powers of less than 25 mW/MHz
      for 50% modulation depth is shown.

PMID- 20134734
TI  - The star coupler: a unique interconnection component for multimode optical
      waveguide communications systems.
AB  - The use of optical waveguides in communications systems may require the
      interconnection of many interactive terminals. The preferred configuration for
      passive interconnection in optical waveguide systems is shown to be a
      configuration termed the Star system. The central interconnecting component, the
      Star coupler, is described, and the performance of a system incorporating it is
      compared to that of an equivalent system using a common optical bus and Tee
      couplers. The Star system is shown to have lower terminal-to-terminal loss,
      easier upgradability, enhanced reliability and survivability, inherent
      bidirectionality, and inherent equivalence of all terminals. Construction of two
      Star couplers is described, and measurements of their performance characteristics
      are reported.

PMID- 20134735
TI  - Three-dimensional unstable resonator calculations with laser medium.
AB  - A numerical procedure that uses an explicit finite difference method to solve the
      wave equation is described. This technique results in a propagation algorithm
      that can accurately propagate an arbitrary electric field through a uniform
      medium or a medium that is nonuniform, transversely flowing, saturable, and
      contains index inhomogeneities. By using the propagation algorithm to propagate
      an arbitrary field back and forth between two resonator mirrors, the three
      dimensional transverse mode and the output beam characteristics for a laser
      resonator can be determined. The advantage of the finite difference method is
      that unlike integral techniques the computational accuracy and efficiency improve
      as the resonator Fresnel number increases. The computational techniques are
      explained, and results for several specific empty cavity confocal unstable
      resonators are presented and compared to results obtained using an established
      calculation technique. The application of the finite difference method to
      inhomogeneous laser media is described, and computational results for an existing
      CO(2) gas dynamic laser are presented and compared to measured data. The medium
      kinetics and shock wave models used in the calculations are described.

PMID- 20134736
TI  - Removal of pedestals and directional ambiguity of optical anemometer signals.
AB  - Laser Doppler anemometry permits, in principle, the measurement of both magnitude
      and direction of components of a particle's velocity vector. Most exiting
      anemometers, however, permit measurements only with a directional ambiguity of
      180 degrees , resulting in errors in certain flow fields. Available methods of
      eliminating the directional ambiguity of Laser Doppler anemometers are reviewed,
      covering frequency shifting of the incident and scattered light beams, the use of
      beams with different polarization properties, and employment of multicolor laser
      beams. The advantages and disadvantages of existing methods are summarized, and
      suggestions for alterations are made. Different techniques used to remove the
      pedestal of laser Doppler anemometer signals are also reviewed. Optical
      techniques should be employed in any advanced optical anemometer system to avoid
      dynamic range limitations by electronic bandpass filters. Suggestions are made
      for advanced optical anemometers employing multielement avalanche photodiodes
      that can be used for simultaneous measurements of two velocity components. These
      anemometers incorporate devices to sense the direction of the velocity components
      and to eliminate optically the pedestal of laser Doppler signals.

PMID- 20134737
TI  - Spherically corrected reflecting objective for unit magnification.
AB  - Cassegrainian-type reflecting objectives are useful as in-line imaging devices
      for fast spectrometer systems. They are inherently free from chromatic
      aberrations and may be corrected for spherical aberration. A particularly simple
      design, consisting of two mirrors with oppositely equal curvatures, is possible
      when unit magnification is desired. This system has zero third-order spherical
      aberration, and all other aberrations are small also. Its main disadvantage is
      the loss due to the central obstruction of the beam, amounting to about 28%
      exclusive of reflection losses. The author is with the Analytical Chemistry
      Division, National Bureau of Standards, Washington, D.C. 20234.

PMID- 20134738
TI  - Computation of RMS Spot Radii by Ray Tracing.
AB  - In a ray trace calculation of the rms radius of the spot formed in the image
      plane of an optical system by a point source object, a decision must be made as
      to how many rays will be traced to obtain the result. As the number of rays is
      increased, the rms spot radius is generally found to decrease, apparently
      approaching a definite lower limit as the number of rays becomes very large. This
      paper examines the question of how many rays must be traced and what their
      geometrical distribution within the aperture should be to approach the limiting
      value of the rms spot radius for an infinite number of rays within an accuracy of
      approximately 1%.

PMID- 20134739
TI  - Gamma-ray imaging with stochastic apertures.
AB  - The spatial distribution of a radioactive fluid can be measured indirectly by
      observing the emerging gamma rays. A method is proposed and analyzed for gamma
      ray imaging by stochastic time modulation and cross-correlation. Theoretical
      comparison is made to collimation and coded aperture techniques in gamma-ray
      image formation. Computed results are presented that illustrate the mean response
      and statistical error characteristics of this technique. Monte Carlo simulations
      are performed as a further verification. Because it relies upon a point-by-point
      reconstruction, rather than upon the integral properties of any particular
      aperture, the time modulation approach is seen to provide a theoretical basis for
      obtaining a smooth three-dimensional point response.

PMID- 20134740
TI  - Wind and refractive-turbulence sensing using crossed laser beams.
AB  - The theory of optical propagation through atmospheric turbulence demonstrates the
      sensitivity of such quantities as log-amplitude variance and covariance to
      strength of refractive turbulence and transverse wind. We exploit this
      sensitivity by using a crossed-path technique to derive path profiles of these
      quantities. The results are insensitive to changes in the spatial spectrum of the
      refractive-index variations. The path resolution is easily varied by changing the
      receiver and transmitter separations and is ultimately limited by signal-to-noise
      considerations. The experimental results for horizontal paths, described here,
      will ultimately be used to indicate the feasibility of profiling on vertical
      paths with passive sources.

PMID- 20134741
TI  - Optimum adaptive imaging imaging through atmospheric turbulence.
AB  - Recent results for the atmospheric mode decomposition are applied to an idealized
      imaging problem in which the receiver has a priori knowledge of the channel
      impulse response and mode decomposition. It is shown that a channel-matched
      filter receiver is essentially optimum and, on the average, achieves diffraction
      limited performance. Furthermore, when the transmitting aperture lies within a
      single isoplanatic patch, this system may be realized without a priori channel
      knowledge by transmitted reference techniques.

PMID- 20134742
TI  - Normal-mode approach to wave propagation in the turbulent atmosphere.
AB  - Recent studies have used the superposition principle (extended Huygens-Fresnel
      principle) to characterize completely the statistics of a field that has
      propagated through a thick slab of turbulent air in terms of the statistics for
      spherical-wave sources. In this paper, we consider the normal-mode decomposition
      associated with this linear system propagation model. In particular, we use the
      statistics of the atmospheric impulse response (Green's function) to show that
      the atmospheric mode decomposition exhibits far-field and near-field regimes very
      similar to those of free-space propagation. The significance of these results for
      optical communication through the atmosphere is briefly discussed.

PMID- 20134743
TI  - Evaluation of r(o) for Propagation Down Through the Atmosphere.
AB  - The concept of the quantity r(o) as a length that measures the effect of
      atmospheric turbulence on optical systems that are wavefront distortion sensitive
      is briefly reviewed. It is pointed out that no precise set of data on r(o) for
      propagation down through the atmosphere has been published. Using astronomical
      seeing data obtained by Hoag and by Meinel it is shown how statistics for r(o)
      can be derived, at least for observatory quality sites. We find that the two sets
      of data are in very good agreement and conclude that r(o) is variable from night
      to night and distributed according to a log-normal distribution. For 0.55-microm
      light and zenith propagation, the median value of r(o), is 0.114 m and changes by
      a factor of 1.36 for occurrences one standard deviation from the median.

PMID- 20134744
TI  - Infrared radiometer for the pioneer 10 and 11 missions to jupiter.
AB  - Pioneer 10 has successfully encountered Jupiter and several of its satellites.
      The two-channel infrared radiometer used to obtain data relating to thermal
      properties of the planet and its atmosphere is described. The instrument features
      a body-fixed, 7.62-cm diam aperture Cassegrainian telescope with reststrahlen
      filters defining the 14-microm to 25-microm and 30-microm to 56-microm bands.
      Detectors are 88-junction evaporated thin-film thermopiles. Stringent weight
      constraints of 2 kg dictated all-beryllium construction. Power Consumption was
      1.2 W.

PMID- 20134745
TI  - Multiple docking adapter window for the s-190 experiment.
AB  - Martin Marietta/NASA subcontracted the design, fabrication, testing, and
      installation of the multiple docking adapter S-190 experiment window assembly to
      Actron. In this paper we primarily treat the thermal-optical analysis aspect of
      the design phase. The window is a pane of BK 7 glass 59.18 cm x 44.91 cm x 4.06
      cm. Though it must meet many mechanical specifications, the optical requirements,
      dictated by the high acuity, distortion-free S-190 multiband camera system, are
      the most severe. Under operating conditions over any 7.6-cm circular area, the
      maximum rms deviation from the best-fitting plane must be less than 12.0 nm, and
      from the reference plane through the entire window, 60.0 nm.

PMID- 20134746
TI  - Far field diffraction patterns of circular gratings.
AB  - The fine structure of the annular images of circular gratings is analyzed in
      terms of diffraction patterns of axicon pairs. Each image arises substantially
      from only one converging and one diverging axicon of equal deflection angle.
      Single main lobe, symmetric double main lobe, and various intermediate asymmetric
      double lobe structures are obtained depending on the phase relationship and
      strengths of the two axicon beams, which in turn depend on the design of the
      circular grating. Approximate expressions are derived for the intensity
      distribution and energy content of the symmetric single and double lobe images.

PMID- 20134747
TI  - High Temperature Absorption in CO(2) at 10.6 microm.
AB  - Measurements of the temperature variation of the resonant absorption coefficient
      in shock heated CO(2) gas (350-1600 K) using a laser source operating on the
      P(20) or P(18) transition are reported. Values obtained are compared with theory
      allowing for mixed mode contributions to absorption as well as dependence of the
      optical broadening cross section on temperature.

PMID- 20134748
TI  - Performance characteristics of single point diamond machined metal mirrors for
      infrared laser applications.
AB  - Single point diamond knives have been used to machine to microinch tolerances.
      This micromachining can also produce optics of high quality. Optical
      micromachining capabilities in terms of materials, shapes, and optical figure are
      discussed. Comparisons are made between micromachined mirrors and superpolished
      surfaces including reflectivity, absorption, scatter, roughness, autocorrelation
      length, and Nomarski microscopy. 10.6-microm pulsed damage data and preliminary
      10.6-microm cw damage investigations are also reported. Micromachined well with
      superpolished samples.

PMID- 20134749
TI  - Multiplexed dispersive spectrometers using reduced background infrared detectors.
AB  - The application of multiplex spectrometry to cryogenically cooled LWIR extrinsic
      photodetectors is limited by system noise. This noise limitation results in a
      detector NEP that is directly proportional to bandwidth. Therefore, multiplex
      schemes that require increased bandwidth are not productive of real advantage.
      However, doubly encoded systems that are based on 2n - 1 or n + N - 1
      measurements have the potential to provide a real throughput gain proportional to
      the number of elements used on the throughput matrix.

PMID- 20134750
TI  - Analytical description of a fabry-perot spectrometer. 3: off-axis behavior and
      interference filters.
AB  - A general expression is derived for a Fabry-Perot spectrometer when one or more
      of the functions entering into its description lack the inherent radial symmetry
      of the fringe pattern about the etalon optical axis. Calculations of the effects
      of these asymmetric functions applicable to densitometry of photographic fringe
      records and vidicon scanning of fringe patterns are given. The theory is also
      applied to interference filters in order to quantitatively explain their behavior
      as they are tilted in order to scan a spectrum. Rather simple approximations to
      the theory are also derived for interference filters that show that both the
      inverse of the peak transmission and the square of the width (normalized to the
      unbroadened filter) are proportional to the square of the product of the tilt and
      field of view angles over the width, in excellent agreement with experimental
      measurements.

PMID- 20134751
TI  - Theoretical comparison of singly multiplexed hadamard transform spectrometers and
      scanning spectrometers.
AB  - We present a general mathematical framework within which the relative performance
      of singly multiplexed Hadamard transform spectrometers (HTS) and conventional
      scanning spectrometers (SS) may be compared. The theoretical multiplex advantage
      (Fellgett advantage) is calculated for spectrometers operating in two spectral
      regions. For the low energy region, i.e., infrared, the determined multiplex
      advantage F is (N/2)((1/2)) (N is tle number of slots), in accordance with
      predictions given by Fellgett. For the high spectral energy region, i.e., uv-vis,
      F = (x/2x )((1/2)), where x is the intensity of the spectal element sought and x
      is the average intensity produced across the whole spectrum. Our predictions are
      verified by computer simulation of various characteristic spectra. Based on these
      results, we arrive at some conclusions concerning the practical application of
      HTS systems.

PMID- 20134752
TI  - Two asymmetric hadamard transform spectrometers.
AB  - We develop the theory of operation for dispersive spectrometers that modulate
      radiation at both the entrance and exit apertures by means of Hadamard codes.
      Specifically, we examine the operation of instruments illuminated by a beam of
      radiation known to be homogeneous. In this case, all spatial information obtained
      in the operation of the instrument can be effectively suppressed at no loss of
      spectral performance and at a considerable reduction in the number of
      measurements that need to be made. A particularly interesting instrument which
      mocks a monochromator is described. The spectrum is directly obtained from the
      data by simply subtracting a constant intensity value from all readings. This
      instrument bears a resemblance to the Girard grill spectrometer. We describe the
      construction and operation of an instrument that has been tested in both modes of
      operation and show some of the spectra obtained.

PMID- 20134753
TI  - Drift in interference filters. Part 1.
AB  - Studies of narrow-band interference filters have shown that two mechanisms exist
      that cause drift to shorter wavelengths. One is dependent on the thermal history
      of the filter, and the other depends on the radiation history. The present paper
      presents experimental results on thermal effects; and it is shown that by a
      proper bake cycle, ZnS-cryolite filters are stable for years if stored at less
      than 38 degrees C.

PMID- 20134754
TI  - Drift in interference filters. 2: radiation effects.
AB  - Studies of peak transmission drift in narrow-band interference filters have shown
      that there exist two mechanisms that cause drift toward shorter wavelengths. One
      is dependent on the thermal history of the filter and is discussed in Part 1 of
      this paper. The other is dependent on the exposure of the filter to radiation.
      For ZnS-cryolite filters of the design [(HL)(4)H(8)(LH)(4)L](3)L(-1), it is
      experimentally demonstrated that the filters are most sensitive to radiation in a
      100-A band centered at approximately 3900 A. The drift rate in the focal plane of
      an f/20 solar image is approximately 3 A/100 h of exposure. Further, it is also
      shown by model calculations that the observed radiation-induced drift is
      consistent with the hypothesis that the optical thickness of ZnS decreases in
      proportion to the radiant energy absorbed.

PMID- 20134755
TI  - Correction of parabolic errors in fabry-perot interferometers.
AB  - Methods are described for correcting parabolic errors in Fabry-Perot
      interferometers using evaporated films and an appropriate shutter. Errors of
      lambda/50 can be readily reduced to less than lambda/400 over 54-mm apertures
      (lambda approximately 550 nm).

PMID- 20134756
TI  - Envelope interferometry for large-scale processing.
AB  - An interferometry system is presented that is useful in large-scale measurements
      such as those of topographic maps. The envelope of a propagating wave is used to
      create the desired fringe patterns, representing range contours, through the
      interference of a light modulation function and an image modulation function. A
      number of variations are shown that either provide altitude contours or place the
      contour information on a spatial frequency carrier. This latter system offers the
      flexibility of electronic processing when the image is scanned. The comparison of
      contour patterns taken at different times provides an accurate indication of
      subtle surface deformations.

PMID- 20134757
TI  - Digital wavefront measuring interferometer for testing optical surfaces and
      lenses.
AB  - A self-scanned 1024 element photodiode array and minicomputer are used to measure
      the phase (wavefront) in the interference pattern of an interferometer to
      lambda/100. The photodiode array samples intensities over a 32 x 32 matrix in the
      interference pattern as the length of the reference arm is varied
      piezoelectrically. Using these data the minicomputer synchronously detects the
      phase at each of the 1024 points by a Fourier series method and displays the
      wavefront in contour and perspective plot on a storage oscilloscope in less than
      1 min (Bruning et al. Paper WE16, OSA Annual Meeting, Oct. 1972). The array of
      intensities is sampled and averaged many times in a random fashion so that the
      effects of air turbulence, vibrations, and thermal drifts are minimized. Very
      significant is the fact that wavefront errors in the interferometer are easily
      determined and may be automatically subtracted from current or subsequent
      wavefrots. Various programs supporting the measurement system include software
      for determining the aperture boundary, sum and difference of wavefronts, removal
      or insertion of tilt and focus errors, and routines for spatial manipulation of
      wavefronts. FFT programs transform wavefront data into point spread function and
      modulus and phase of the optical transfer function of lenses. Display programs
      plot these functions in contour and perspective. The system has been designed to
      optimize the collection of data to give higher than usual accuracy in measuring
      the individual elements and final performance of assembled diffraction limited
      optical systems, and furthermore, the short loop time of a few minutes makes the
      system an attractive alternative to constraints imposed by test glasses in the
      optical shop.

PMID- 20134758
TI  - Double-beam two-channel wavelength-modulated reflectometer.
AB  - A double-beam wavelength-modulated reflectometer utilizing a single detector and
      without a reflectivity reference has been described. Separate electronic channels
      are used for the two wavelengths at which the reflectometer alternatively
      operates. The gain of one of the channels is controlled by feedback to eliminate
      the instrumental background. The derivative and conventional reflectivity are
      measured simultaneously. The influence of the photomultiplier dark current and
      scattered light on the accuracy and of some design parameters on the SNR have
      been evaluated. The system has been checked by measuring the derivative and
      conventional reflectivity spectrum of GaAs.

PMID- 20134759
TI  - Wavelength Standards for Use with a BRV Source.
AB  - The BRV source, which emits continuum light in far uv wavelengths, is suitable
      for use as the background continuum in studies of absorption spectra. Methods of
      generating wavelength standards for these spectra are discussed, and a list is
      given of wavelengths of emission lines that can be generated in the source and
      are useful as secondary standards.

PMID- 20134760
TI  - Far Infrared Transmission and Reflection of Irtran 1 through Irtran 6 at Low
      Temperatures.
AB  - Transmission and reflection measurements in the infrared region between 340 and
      40 cm(-1) are presented for Irtrans 1-6. Measurements have been performed at room
      temperature and at liquid nitrogen and liquid helium temperatures.

PMID- 20134761
TI  - Physical model for predicting grinding rates.
AB  - When grinding an optical surface, the material removal rate depends linearly upon
      pressure and velocity and upon a proportionality constant which accounts for
      differences in material properties. A physical description of the grinding
      process has been postulated which results in the linear pressure and velocity
      relationships and which also allows the value of the proportionality constant to
      be determined from a knowledge of material properties alone. Previous attempts at
      predicting material removal rely strictly upon experimental data to determine the
      proportionality constant. The postulated description incorporates the combined
      effects of many individual abrasive particles to statistically determine the
      proportionality constant in terms of abrasive size and the breaking stress of the
      glass. A simple example indicates that the result is consistent with experiment.

PMID- 20134762
TI  - Prediction of nighttime driving visibility from laboratory data.
AB  - The application of laboratory threshold visibility data to the subject of driving
      visibility with heat absorbing glass has been reviewed in an attempt to resolve
      excessive differences between calculated predictions and road test observations.
      New calculations are described that yield predicted losses of visibility distance
      due to the use of heat absorbing glass rather than regular glass in automobile
      windshields. The predicted losses agree satisfactorily with the observed losses
      for road tests, which average proximately 3%. The new calculations have made use
      of a revised visual exposure interval of ? sec corresponding with five visual
      fixational pauses per second and a new simulation model that assumes that the
      target-to-background contrast increases with reduced headlamp-to-target distance.

PMID- 20134763
TI  - Annular Apertures with High Obstruction: Autho's Reply to Comment.

PMID- 20134764
TI  - Annular apertures with high obstruction: comment.

PMID- 20134765
TI  - Optical antenna gain. 2:receiving antennas. Errata.

PMID- 20134767
TI  - Applied optics of optics and opticists.

PMID- 20134766
TI  - Fourier transform lens: a misnomer.

PMID- 20134768
TI  - Patents.
AB  - 3,711,199; 3,716,286; 3,716,287; 3,718,074; 3,720,779; 3,723,010; 3,724,943;
      3,729,634; 3,731,265; 3,731,993; 3,739,093; 3,740,111; 3,752,556; 3,754,814;
      3,756,683; 3,158,186; 3,764,979; 3,784,310; 3,784,377; 3,785,724; 3,786,366;
      3,787,112; 3,788,745; 3,791,719; 3,791,720; 3,802,765; 3,803,510; 3,804,494;
      3,804,496; 3,804,528; 3,804,531; 3,804,619; 3,805,186; 3,806,231; 3,806,237;
      3,806,725; 3,806,871; 3,807,835; 3,807,836; 3,809,457; 3,810,042; 3,810,693;
      3,811,095; 3,811,748; 3,811,749; 3,811,754; 3,813,158; 3,813,552; 3,813,611.

PMID- 20134769
TI  - Design of simple rotating stigmatic concave grating monochromators.

PMID- 20134770
TI  - Ground-Based Determination of Atmospheric Radiance for Correction of ERTS-1 Data.

PMID- 20134771
TI  - Distributed-Feedback Double-Heterostructure GaAs Injection Laser with Fundamental
      Grating.

PMID- 20134772
TI  - The abbe or the duffieux.

PMID- 20134773
TI  - Optical activities in industry.

PMID- 20134774
TI  - PbS-Al Selective Solar Absorbers.

PMID- 20134775
TI  - How lorenz might have viewed the computation of the angular functions occurring
      in his theory.

PMID- 20134776
TI  - Expansion of the mie phase function in legendre polynomials.

PMID- 20134777
TI  - Simplified analytical formulas for thermal blooming.

PMID- 20134778
TI  - Propagation constants in diffused planar optical waveguides.

PMID- 20134779
TI  - Mode selective filtering by a coupling mechanism between glass fiber and thin
      film slab waveguide.

PMID- 20134780
TI  - Real Time Display of Velocity Distribution on a Surface by Using Ultrasonic Laser
      Light Frequency Shifter and TV System.

PMID- 20134781
TI  - Two-dimensional white light coherence interferometer.

PMID- 20134782
TI  - Computer generated hologram; null lens test of aspheric wavefronts.

PMID- 20134783
TI  - Analysis of a computer-generated binary-phase hologram.

PMID- 20134784
TI  - Modulated holographic grating.

PMID- 20134785
TI  - Bleached phase hologram containing nonsilver metal compound.

PMID- 20134786
TI  - Metal dithizonates: a new material for recording transient absorption holograms.

PMID- 20134787
TI  - Light Intensity of the Fundamental TEM(oo) Mode of a He-Ne Gas Laser Without
      Brewster Windows: Achievement of a Polarized Rectilinear Laser Beam of Stable
      Intensity.

PMID- 20134788
TI  - Low-Temperature Far-infrared Windows.

PMID- 20134789
TI  - Marechal intensity criteria modified for gaussian beams: errata.

PMID- 20134790
TI  - Mode calculations in unstable resonators with flowing saturable gain. 1:hermite
      gaussian expansion.
AB  - We present a procedure for calculating the three-dimensional mode pattern, the
      output beam characteristics, and the power output of an oscillating high-power
      laser taking into account a nonuniform, transversely flowing, saturable gain
      medium; index inhomogeneities inside the laser resonator; and arbitrary mirror
      distortion and misalignment. The laser is divided into a number of axial
      segments. The saturated gain-and-index variation. across each short segment is
      lumped into a complex gain profile across the midplane of that segment. The
      circulating optical wave within the resonator is propagated from midplane to
      midplane in free-space fashion and is multiplied by the lumped complex gain
      profile upon passing through each midplane. After each complete round trip of the
      optical wave inside the resonator, the saturated gain profiles are recalculated
      based upon the circulating fields in the cavity. The procedure when applied to
      typical unstable-resonator flowing-gain lasers shows convergence to a single
      distorted steady-state mode of oscillation. Typical near-field and far-field
      results are presented. Several empirical rules of thumb for finite truncated
      Hermite-Gaussian expansions, including an approximate sampling theorem, have been
      developed as part of the calculations.

PMID- 20134791
TI  - Laser resonators with polarizing elements-eigenstates and eigenvalues of
      polarization.
AB  - A matrix method is used to calculate losses and eigenpolarizations of laser
      resonators containing linear elements (e.g., mirrors, laser rods, Pockels cells,
      and stack-plate polarizers). Experiments confirm the prediction that for the
      combination of a Pockels cell and a stack-plate polarizer, a critical voltage
      exists, above which the induced loss is no longer voltage dependent, and the in
      cavity extinction ratio of the Pockels shutter is determined by the degree of
      polarization achieved in the stacked plates. The steep rise of the losses near
      the critical voltage pointsation at moderate voltages points out the possibility
      of modulating the loss with a fair degree of modulation at moderate voltages.

PMID- 20134792
TI  - Analysis of Optically Pumped CO(2)Laser.
AB  - The operating characteristics of an optically pumped CO(2) laser are analyzed by
      a mathematical procedure that treats the transport of the pumping radiation
      according to the method of Milne. Simple expressions are obtained for laser power
      output and efficiency vs such operating parameters as initial pressure, species
      concentrations, output mirror transmittance, linewidth of the pumping radiation,
      and cavity dimensions. Optimum power output efficiencies appear to be comparable
      with those of electrical discharge and chemically pumped CO(2) lasers.

PMID- 20134793
TI  - Parasitic suppression in large aperture nd:glass disk laser amplifiers.
AB  - Threshold conditions for bulk and surface parasitic oscillations, which may limit
      energy storage in large aperture Nd:glass disk lasers, have been developed as a
      function of material parameters. An expression describing the energy storage
      distribution within a disk was used to determine the mode that will be most
      limiting for a particular disk design. Additional modes that may be limiting in
      special cases were identified and their effects evaluated. These results are
      useful in developing disk laser designs that minimize parasitic effects.

PMID- 20134794
TI  - Spectral line selection of carbon monoxide lasers.
AB  - An intracavity water vapor cell was used to perform spectral line selection of
      carbon monoxide lasers. The technique was demonstrated with a low pressure
      longitudinal discharge laser operating in the cw and repetitive Q- switched modes
      and with an electron beam stabilized pulsed laser. The cell containing an
      appropriate amount of water vapor limited laser action in a vibrational band to
      those rotational lines having predicted high atmospheric transmittance.

PMID- 20134795
TI  - Small dye laser in a semiunstable resonator pumped by an argon-jet guided spark.
AB  - An argon-jet guided spark of 1-cm length has been constructed, and a small dye
      laser was pumped by that spark at 150 Hz with 60-nsec pulses. The use of high dye
      concentrations provided enough gain over a short pathlength. As a consequence of
      the high concentration and side pumping the cross section of the pumped volume
      measures only 1.5 x 0.1 mm(2) . This laser of rectangular, cross section lases in
      one transversal mode due to the application of a novel resonator configuration
      that is unstable in the vertical plane and stable in the horizontal. An analysis
      of the factors determining the threshold and of the spatial configuration of this
      astigmatic mode is given.

PMID- 20134796
TI  - Kinetic Model and Computer Simulation of Continuous Wave DF-CO(2) Chemical
      Transfer Lasers.
AB  - A nonequilibrium model has been used to simulate successfully experimental data
      obtained on two different DF-CO(2) chemical transfer lasers. The sensitivity of
      the model to changes in the reaction rate constants, to mixing, and to F atom
      surface recombination has been investigated. The model was found to provide
      reasonable agreement with the known experimental facts relating to cw DF-CO(2)
      chain reaction laser flow fields. It was found that considerable simplification
      of the chemical model is possible at the sacrifice of some analytical precision.

PMID- 20134797
TI  - Transverse-Flow Quasi-cw HF Chemical Laser: Design and Preliminary Performance.
AB  - A small transverse-flow HF chemical laser has been constructed using a large
      volume microwave plasma generator for the production of F atoms. The F atoms
      react with hydrogen to form the lasing HF molecules. The active medium is about 5
      cm long, and the maximum average laser power was found to be 560mW for all lines.
      Three laser lines with wavelengths 2.61 microm, 2.64 microm, and 2.73 microm were
      observed. The time-varying laser transition profile closely resembles the density
      profile of the excited fluorine atoms in the plasma. Both profiles are greatly
      affected by changes in flow conditions.

PMID- 20134798
TI  - Remote atmospheric sensing with an airborne laser absorption spectrometer.
AB  - A laser absorption spectrometer, using an ir laser transmitter and a heterodyne
      radiometer, can be used from an aircraft or spacecraft to measure altitude
      profiles of air pollutants and other atmospheric constituents. The technique
      involves measurement of differential absorption at several wavelengths, using the
      diffusely reflecting earth's surface to provide a return signal. The pressure
      broadening of absorption lines allows one to discriminate between high and low
      altitude absorbers. Application of the technique to measurements of ozone, nitric
      oxide, and water vapor are presented. CO(2) and CO lasers are considered as
      transmitters. The discussion includes altitude resolution limitations,
      atmospheric temperature dependence, and frequency stability requirements of the
      instrument.

PMID- 20134799
TI  - CO(2) Laser Absorption Coefficients for Determining Ambient Levels of O(3),
      NH(3), and C(2)H(4).
AB  - A carbon dioxide laser source was used to determine absorption coefficients for
      dilute absorber-air mixtures at wavelengths corresponding to several vibration
      rotation lines in each branch of the 00 degrees 1-02 degrees 0 band at 9.4 microm
      and the 00 degrees 1-10 degrees 0 band at 10.4 microm. For all samples the total
      pressure was 1 atm and the temperature was 300 K; the concentrations ranged from
      10 ppm (parts per million by volume) to 357 ppm for NH(3) and C(2)H(4), and from
      10 ppm to 80 ppm for O(3). The absorption coefficients are tabulated, and the use
      of selected laser lines in monitoring ambient concentrations is discussed.

PMID- 20134800
TI  - Atmospheric Gas Absorption at DF Laser Wavelengths.
AB  - The absorption of twenty-four DF laser wavelengths ranging from 3.6128 microm
      P(1)(6) to 4.0464 microm P(3)(11) was measured for CH(4) , N(2)O, CO(2), and HDO
      vapor. Total absorption was calculated for the lines for each of these absorbing
      gases and for the N(2) and H(2)O continua independently and collectively for two
      representative transmission paths (midlatitude summer model); i.e., a vertical
      path from sea level to the edge of the atmosphere containing 2.93 cm precipitable
      water and a horizontal 8.0-km path at sea level at 14.2-Torr water vapor partial
      pressure (11.2 cm precipitable water). Transmission was >90% for twelve lines in
      the vertical path and >65% for thirteen lines in the horizontal path. A
      comparison of the measured absorption coefficients was made with calculated
      values of McClatchey and Selby for seventeen lines. Good agreement was obtained
      with most lines, the worst within a factor ~2 of predicted values.

PMID- 20134801
TI  - Phase Difference and Angle-of-Arrival Fluctuations in Tracking a Moving Point
      Source.
AB  - The correlation function and power spectrum of phase difference fluctuations and
      angle-of-arrival fluctuations are calculated for tracking a moving spherical wave
      optical source through atmospheric turbulence. For Kolmogorov turbulence, it is
      shown that, in order to freeze effectively the received wavefront, the scanning
      frequency must be essentially equal to the highest frequency contained in the
      power spectrum.

PMID- 20134802
TI  - Size-refractive index distribution of clear coastal water particulates from light
      scattering.
AB  - Simultaneous measurements of the size distribution and volume scattering function
      of particles in clear coastal water are used to estimate a particle size
      refractive index distribution. Various possibilities of the refractive index
      distribution and the observed particle distribution are studied systematically
      using Mie theory. The resulting model has minerals in mid-sizes and organic
      material in large and small sizes, but does not yield the correct dependence of
      scattering on wavelength. By assuming the existence of minerals or organics in
      sizes too small to be measured by the particle counter, two other models are
      developed, both of which yield acceptable wavelength dependence of scattering.
      The results of the three models are combined to provide limits on the size
      refractive index distribution of the particles. Within these limits, volume
      scattering functions computed for the particles show good agreement with the
      measurements.

PMID- 20134803
TI  - Refractive index and diameter determinations of step index optical fibers and
      preforms.
AB  - A new method to determine the index of refraction in combination with the
      diameter of the cores of stepindex optical fibers and preforms is presented. The
      technique is based on an analysis of the backscattered light when a beam from a
      cw laser impinges transversely upon the fiber or preform. A geometrical-optics
      analysis shows that, under appropriate assumptions, a combination of the
      refractive indexes and the radii of the core and cladding can be determined from
      unique characteristics of the backscattered radiation pattern. The theory is
      compared to experimental observations with excellent agreement.

PMID- 20134804
TI  - Optical-waveguide band-rejection filters: design.
AB  - A method for designing optical-waveguide band-rejection filters is presented that
      allows side-lobe levels to be reduced by several orders of magnitude while the
      rolloff rate of the response characteristics is not appreciably degraded. The
      method is based upon the control of the shape of the perturbation-amplitude
      envelope. We discuss in detail the particular case where the coupling coefficient
      of the waveguide filter takes the form of a modified raised cosine function along
      the length of the waveguide. Side-lobe level and rolloff can be traded off by
      appropriately choosing the index p of the function. Design curves are included
      that allow the optimization of filter responses for side-lobe levels or rolloff
      characteristics.

PMID- 20134805
TI  - Airborne laser Doppler velocimeter.
AB  - A CO(2) laser Doppler detection system has been developed to measure remotely the
      true airspeed of an aircraft. The system uses a 50-W sealed-off CO(2) laser in a
      homodyne detection system employing a collinear optical telescope, a HgCdTe
      detector, and a frequency tracking loop. The system was successfully flight
      tested on a NASA Convair 990 research aircraft during December 1971 and June
      1972. The results indicate that an airspeed measurement under clear weather
      conditions is feasible up to an altitude of 3000 m with an error of less than
      0.5%.

PMID- 20134806
TI  - High resolution luminescence spectrometer. 2:data treatment and corrected
      spectra.
AB  - In Part 1 [Appl. Opt. 12, 1286 (1973)] we described the design of a high
      resolution luminescence spectrometer for research purposes. In this paper the
      computer processing of its digital output is discussed. The data treatment is
      based upon statistical concepts. Subroutines for wavelength calibration, dark
      count correction, data smoothing, and curve presentation have been developed.
      Corrected emission and excitation spectra may be obtained with additional
      calibration data, and relative quantum yields may be determined. The final
      luminescence spectra are plotted with their corresponding standard deviations.

PMID- 20134807
TI  - Chirped fourier spectroscopy. 1:dynamic range improvement and phase correction.
AB  - Chirping is the deliberate dispersion of the frequencies in a signal to remove a
      strong central peak. In a Fourier spectrometer, chirping improves dynamic range.
      For typical applications, the improvement is equivalent to about 16 dB in SNR. A
      very large nonlinear phase correction is required, but this is shown to be
      surprisingly simple to achieve in practice.

PMID- 20134808
TI  - Adjustable aperture stop to control the divergence and orientation of the beam
      emerging from a vacuum ultraviolet monochromator.
AB  - An adjustable aperture stop for use in controlling the direction and angular
      divergence of the beam of radiant flux emerging from a MacPherson 225 VUV
      monochromator is described. Such a stop facilitates measurements of specular
      reflectance vs angle of incidence and measurements of diffraction grating
      efficiency. A discussion of the degree of control exercised by the aperture over
      the beam cross section is given that is applicable to any monochromator fitted
      with an aperture stop. For this application, the distance from the grating to the
      aperture stop is larger than the grating focal length. The result is an imaging
      effect that provides sharper definition of the beam cross section when the
      aperture stop is between the entrance slit and grating than if the stop is
      between the grating and exit slit. This sharp definition persists up to distances
      of several meters beyond the exit slit and is useful when measuring the
      efficiency of concave diffraction gratings. A fixed direction of the beam from
      the MacPherson i strument can only be obtained with the aperture between the
      grating and exit slit which results in some loss of definition of the beam cross
      section. However, as long as the pathlength beyond the exit slit is restricted to
      a few tens of cm, the definition is sufficiently good for measurements of
      reflectance vs angle of incidence.

PMID- 20134809
TI  - Optimal filter design for annular imaging.
AB  - Filters of the type exp(in theta)sgn J(n)(z(o)r) with theta the azimuthal angle
      and r the radial coordinate in the filter plane, are shown to maximize the energy
      content in a narrow annular image of radius z(o) with respect to incident energy.
      The simplest optimal filter, sgnJ(o)(z(o)r), is well approximated by the binary
      circular phase grating sgn cos(z(o)r - pi/4). The single lobe of the first order
      image of this filter contains 46% of the incident energy within the half-width
      0.4lambdaf/a, centered around the image radins Nlambdaf/(2a), where N
      approximately z(o)/pi is the number of filter sections.

PMID- 20134810
TI  - Holographically generated lens.
AB  - A holographic lens has been made that utilizes some of our earlier work on
      holographic aberration correction [J. E. Ward, D. C. Auth, and F. P. Carlson,
      Appl. Opt. 10, 896 (1971)]. The lens properties are obtained by
      interferometrically recording a plane wave and a pinhole generated spherical
      wave. The theoretical analysis is followed by the results of the Ronchi lens
      test, Fourier transformation of a grating, and imaging of a test picture.

PMID- 20134811
TI  - Aberrations of ellipsoidal reflectors for unit magnification.
AB  - Ellipsoidal reflectors are useful for the 1:1 imaging of small objects without
      spherical and chromatic aberration. The magnitude of the off-axis aberrations of
      such reflectors is computed by application of Fermat's principle to the
      Hamiltonian point characteristic. The limiting form of the mirror aperture for
      which these aberrations do not exceed a set tolerance is an ellipse whose
      semiaxes depend on object size and angle of incidence.

PMID- 20134812
TI  - Improved thermoplastic-photoconductor devices for holographic recording.
AB  - Thermoplastic-photoconductor devices are attractive for holographic recording
      because of their relatively high sensitivities, efficient holograms, and record
      erase capabilities. Recent improvements in charging techniques and in the
      thermoplastic materials should increase the utility of these devices. Charge was
      applied from a transparent electrode located parallel to and at a small distance
      from the thermoplastic surface; charging was rapid and uniform without moving
      parts. Thermoplastics synthesized by polymerizing mixtures of styrene and
      methacrylates were capable of over 5000 record-erase cycles. Measurements of
      holographic recording and reconstruction parameters are presented to lend insight
      to the operation of these devices.

PMID- 20134813
TI  - Advances in bleaching methods for photographically recorded holograms.
AB  - A new, dry method for converting photographically recorded amplitude holograms to
      high diffraction efficiency phase holograms is described. The dry method involves
      the application of elemental bromine or chlorine. The bromine vapor bleaching of
      transmission holograms produced efficiencies of 70.8% in dry film and 75.5% in
      water swelled layers. Index modulations of 0.033 have been observed. Reflection
      hologram efficiencies of 73% were obtained. The stability of the bromine vapor
      bleached holograms to printout is superior to all previous methods.

PMID- 20134815
TI  - Applied optics of optics and opticists.

PMID- 20134814
TI  - Removal of seeing and instrumental blur effects from astronomical scanner
      observations.
AB  - The Phillips-Twomey method for solving simultaneous integral equations is applied
      to the problem of removing blur effects arising from atmospheric and instrumental
      sources from astronomical observations made with photoelectric area-scanning
      instruments. Details of the method and the effects of observational errors on the
      quality of the results are discussed in the context of applications to actual
      observations of stars and the planet Saturn.

PMID- 20134816
TI  - Patents.
AB  - 3,810,040; 3,810,041; 3,806,226; 3,815,036; 3,820,898; 3,822,409;

PMID- 20134817
TI  - Diffraction grating ruling engine with piezoelectric drive.

PMID- 20134818
TI  - Optical activities in industry.

PMID- 20134819
TI  - Proposed distributed feedback crystal cavities for x-ray lasers.

PMID- 20134820
TI  - Methods for Compensating the Nonlinearity in the Diffraction Angle in TeO(2)
      Abnormal Bragg Deflectors.

PMID- 20134822
TI  - Laser anemometer for large high velocity particles.

PMID- 20134821
TI  - Holmium 2.06-microm Laser Spectral Characteristics and Absorption by CO(2) Gas.

PMID- 20134823
TI  - Distortion losses in cabled optical fibers.

PMID- 20134824
TI  - Lucite as a Recording Material in SEM Holography.

PMID- 20134825
TI  - Four-exposure hologram moire interferometry and speckle-pattern interferometry: a
      comparison.

PMID- 20134826
TI  - Dual Index Holographic Contour Mapping over a Large Range of Contour Spacings.

PMID- 20134827
TI  - Determination of refractive index in inhomogeneous axisymmetric media from
      refraction angle measurements.

PMID- 20134828
TI  - Modified technique for determining the wavelength-sensitivity curve of a
      spectrofluorimeter.

PMID- 20134829
TI  - Light scattering by a spheroidal particle.
AB  - The solution of electromagnetic scattering by a homogeneous prolate (or oblate)
      spheroidal particle with an arbitrary size and refractive index is obtained for
      any angle of incidence by solving Maxwell's equations under given boundary
      conditions. The method used is that of separating the vector wave equations in
      the spheroidal coordinates and expanding them in terms of the spheroidal
      wavefunctions. The unknown coefficients for the expansion are determined by a
      system of equations derived from the boundary conditions regarding the continuity
      of tangential components of the electric and magnetic vectors across the surface
      of the spheroid. The solutions both in the prolate and oblate spheroidal
      coordinate systems result in a same form, and the equations for the oblate
      spheroidal system can be obtained from those for the prolate one by replacing the
      prolate spheroidal wavefunctions with the oblate ones and vice versa. For an
      oblique incidence, the polarized incident wave is resolved into two components,
      the TM mode for which the magnetic vector vibrates perpendicularly to the
      incident plane and the TE mode for which the electric vector vibrates
      perpendicularly to this plane. For the incidence along the rotation axis the
      resultant equations are given in the form similar to the one for a sphere given
      by the Mie theory. The physical parameters involved are the following five
      quantities: the size parameter defined by the product of the semifocal distance
      of the spheroid and the propagation constant of the incident wave, the
      eccentricity, the refractive index of the spheroid relative to the surrounding
      medium, the incident angle between the direction of the incident wave and the
      rotation axis, and the angles that specify the direction of the scattered wave.

PMID- 20134830
TI  - Transient thermal blooming of long laser pulses.
AB  - Existing theory for stationary laser pulse propagation in absorbing media for
      times greater than the acoustic transit time is compared with experiments.
      Collimated and focused Gaussian beams as well as unstable resonator type beams
      are investigated. Good agreement is reached for all experimental conditions for
      collimated beams, and at higher energy deposition significant deviations are
      observed for focused beams.

PMID- 20134831
TI  - Effect of collision narrowing on atmospheric transmittance.
AB  - The effect of collision narrowing on inhomogeneous, long-path atmospheric
      transmittance is discussed. The different temperature and pressure dependence of
      the collision narrowing and the collision broadening contributions to the
      absorption line shape can result in a significant change in calculated values of
      both the absolute and relative transmitted intensity. Illustrative calculations
      are presented for a narrow-band source that is resonant with selected absorption
      lines of CO(2) and is transmitted along a variety of atmospheric paths.

PMID- 20134832
TI  - Detection probabilities for fluctuating infrared targets.
AB  - Probability density functions for the projected area of a tumbling or precessing
      target are employed as prior distributions in the derivations of signal plus
      noise distributions for an ir scanner. The analysis treats several cases for
      known and unknown pulse arrival times using a matched filter and also an
      unspecified filter, where the sensor noise is stationary and Gaussian. The signal
      pulse shape is variously Gaussian or unspecified. The paper also provides the
      characteristic functions and detection probabilities corresponding to the signal
      plus noise densities.

PMID- 20134833
TI  - Ground illumination from a turbid cloudless sky.
AB  - An attempt is made to develop a set of empirical equations for the relationship
      between skylight illuminance, turbidity, and solar altitude under the condition
      of a cloud free sky. The maximum possible illuminance from a cloud-free sky is
      estimated using these equations. The illuminances are stated in relation to the
      illuminance produced by a Rayleigh sky. An improved approximation for Bemporad's
      airmass function is used in the computations.

PMID- 20134834
TI  - Lidar measurement of temperature: a new approach.
AB  - It is shown that the thermal distribution of rotational states within a molecular
      absorption band of a gas can be probed by means of lidar differential absorption
      to obtain measurements of the gas temperature. A technique for exploiting this is
      described; and preliminary calculations indicate that, although relatively weak
      absorptions are involved, sensitivities should be sufficient for profile
      measurements of temperature in the atmosphere.

PMID- 20134835
TI  - Self-guiding flashlamp-pumped dye lasers.
AB  - A simple analysis of light amplification in media with inhomogeneous profile of
      the complex refractive index is carried out. The results are used to account for
      the waveguide effects observed in superradiant dye lasers with flashlamp
      excitation and to discuss the basic operations of some new dye laser
      configurations recently developed.

PMID- 20134836
TI  - Flashlight-size external cavity semiconductor laser with narrow-linewidth tunable
      output.
AB  - We describe the construction of a compact and relatively inexpensive external
      cavity to be used with III-V compound semiconductor injection lasers. The
      operation of a typical GaAs diode in the cavity and some of the limiting
      performance factors are discussed.

PMID- 20134837
TI  - Extension of 3p ? 3s ion lasers into the vacuum ultraviolet region.
AB  - The feasibility of extending existing near-ultraviolet ion lasers into the vacuum
      ultraviolet spectral region is analyzed with a simplified three-state model.
      Single-pass amplification in a laser-produced plasma of reasonable length, pump
      power, and rise-time requirements is predicted, especially for high electron
      temperatures. The results are intended to serve as a basis and incentive for
      detailed numerical modeling and for experiments.

PMID- 20134838
TI  - Characteristics of deterministic phase codes for holography.
AB  - Phase coding techniques are useful for lowering the dynamic range of the
      amplitude distribution at the hologram plane. In this paper the characteristics
      of the deterministic phase codes such as Frank codes and Schroeder codes are
      considered and a hologram is made with the phase shifter whose phase distribution
      is given by Frank codes. From these results the optical properties of the
      deterministic phase codes are made clear. Moreover Frank codes are applied to
      make the kinoform, and their effects are made clear when compared with random
      phase codes.

PMID- 20134839
TI  - Removal of instrument signature from mariner 9 television images of Mars.
AB  - The Mariner 9 spacecraft was inserted into orbit around Mars in November 1971.
      The two vidicon camera systems returned over 7300 digital images during orbital
      operations. The high volume of returned data and the scientific objectives of the
      Television Experiment made development of automated digital techniques for the
      removal of camera system-induced distortions from each returned image necessary.
      This paper describes the algorithms used to remove geometric and photometric
      distortions from the returned imagery. Enhancement processing of the final
      photographic products is also described.

PMID- 20134840
TI  - Measurement of strain distribution in plane metal plate by optical spatial
      filtering.
AB  - A new quantitative measurement of strain distributions is performed by optical
      spatial filtering in an optical differentiation system. In this method, the
      strain distribution can be converted to the light intensity distributions in the
      image plane, and three strain components can be obtained by a microphotometric
      method from only a single specimen without time-consuming numerical calculations,
      such as in Moire or photoelastic photoelastic methods. An experimental example is
      performed in order to show the practical usefulness of the present method, and
      some considerations on deterioration in the fidelity of the system performance
      are also given.

PMID- 20134841
TI  - Transfer requirements for target radiance simulation in optical projection
      simulators.
AB  - Valid simulation of target scenes requires spatial, dynamic, and radiance
      simulation fidelity. In this paper, only the target radiance (radiant sterance)
      and -radiance contrast simulation are analyzed, the spatial and dynamic aspects
      considered as being separate image transfer problems. Furthermore, only
      projection simulation techniques are investigated. The functional relationship
      between real-target radiant sterance (radiance) and required simulator source
      sterance is derived from the knowledge of the radiant sterance of the real
      target, the transfer function and throughput factors of the optics, and the
      spectral responsivity of the transfer medium recording the target image.
      Logarithmic and linear exposure-density mechanisms are considered. It turns out
      that the required simulator source sterance is essentially a function of the
      target sterance, and the gamma and exposure in the target image recording
      mechanism. It is independent of target sterance for the logarithmic exposure
      density mechanism if the product of the two gamma values assumed is equal to
      unity.

PMID- 20134842
TI  - Characteristic fringe function for time-average holography of periodic
      nonsinusoidal vibrations.
AB  - In this paper the characteristic fringe function of hologram interferometry has
      been evaluated for the case of periodic, nonsinusoidal vibrations represented by
      a Jacobian elliptic function. To consider the reconstructed holographic image of
      an object, use has been made of an equation derived from considerations of the
      effect of motion on coherence. Graphical representation of the fringe irradiance
      distribution in the reconstructed image is given. It is shown that, as the motion
      departs from pure sinusoidal form, the intensity of the fringes increases
      considerably as compared with that for a pure sinusoidal case.

PMID- 20134843
TI  - Holographic Doppler imaging of rotating objects.
AB  - The Doppler frequency shift of coherent light reflected from rotating objects is
      used to obtain one-dimensional resolution much greater than the classical limit
      for aperture limited imaging systems. The Doppler information is processed by
      using the temporal and spatial filtering properties of modulated-referencewave
      holograms. The holographic reconstruction is a superresolved image. Resolution
      improvements greater than 200 times the classical limit were obtained at good
      signal-to-noise ratios.

PMID- 20134844
TI  - Evaluation of large aberrations using a lateral-shear interferometer having
      variable shear.
AB  - A variable shear lateral shearing interferometer consisting of two
      holographically produced crossed diffraction gratings is used to test
      nonrotationally symmetric wavefronts having aberrations greater than 100
      wavelengths and slope variations of more than 400 wavelengths/diameter.
      Comparisons are made with results of Twyman-Green interferometric tests for
      wavefront aberrations of up to thirty wavelengths. The results indicate that
      small wavefront aberrations can be measured as accurately with the lateral-shear
      interferometer as with the Twyman-Green interferometer and that aberrations that
      cannot be measured at all with a Twyman-Green interferometer can be measured to
      about 1% accuracy or better.

PMID- 20134845
TI  - Focusing Effects in Interferometric Analysis of Graded-index Optical Fibers.
AB  - The effects of ray bending due to graded refractive-index profiles have been
      studied in relation to the measurement of optical-fiber refractive-index profiles
      by microscopic interferometric techniques. In particular, the wavefront curvature
      produced by a simple parabolic profile has been calculated analytically. It is
      concluded that profile measurements by currently used methods require samples for
      which the fiber thickness (length) is much less than the effective focal length
      of the fiber. For parabolic profile fibers with diameter d greater, similar 100
      microm, this poses no problem; however, for small-core versions of this fiber,
      sample thicknesses of 10-15 microm may be required and an alternate measurement
      technique is described. Interferograms made on a Leitz transmitted-light
      interference microscope are included in illustrations.

PMID- 20134846
TI  - Low-Loss FEP-Clad Silica Fibers.
AB  - Easy-to-fabricate, low-loss optical fibers are described that consist of a pure
      fused silica core surrounded with a loosely fitting, extruded, FEP cladding tube.
      Because of their large numerical aperture (NA), these fibers are particularly
      well suited for the transmission of the incoherent light emitted by light
      emitting diodes. Whereas the losses approached those of the core material for
      small angle excitation (i.e., 7.6 dB/km at 0.8 microm for a Suprasil 2 fiber of
      230-m length), they increased to 14 dB/km for a steady-state NA of 0.3. The
      measured pulse dispersion of up to 30 nsec agrees well with the expected 24 nsec
      for a stepindex fiber with an NA of 0.3.

PMID- 20134847
TI  - Dispersion-optimized optical single-mode glass fiber waveguides.
AB  - The optical dispersion in singly clad dielectric monomode waveguides is
      calculated by taking into account the frequency dependence of the refractive
      indices of the core and the cladding materials. The total dispersion is composed
      of the material dispersion and the dispersion of the waveguide structure. Fibers
      can be optimized in such a way that these two portions have opposite signs. The
      portion due to material dispersion, however, is about 2 orders of magnitude
      greater than that due to waveguide structure dispersion (considering typical
      glasses at wavelengths of 0.9 microm and 1.06 microm). Thus, complete
      compensation of these portions is impossible, and the fibers cannot be made
      dispersion-free at these wavelengths. The total dispersion at 1.06 microm,
      however, is smaller than at 0.9 microm by a factor of ?

PMID- 20134848
TI  - Excitation of the fundamental and low-order modes of optical fiber waveguides
      with gaussian beams. 2: offset beams.
AB  - The excitation efficiencies of the dominant and low-order modes in an optical
      fiber are theoretically determined for an incident Gaussian beam that is offset
      with respect to the fiber axis. The excitation efficiencies are shown to be
      strongly influenced by both the numerical aperture of the fiber and the wavefront
      curvature of the incident beam.

PMID- 20134850
TI  - Moire topography.
AB  - Using geometrical optics, an oblique-shadow method is shown to generate moire
      patterns, which under specific conditions can be interpreted as contour lines of
      the surface. The oblique-shadow method consists of illuminating a viewing grid
      with equal spaced parallel lines. The light can be either a point source or
      parallel light, the observation point can be either at finite distance or at
      infinity. Conditions for which moire patterns become contour lines of the surface
      are given.

PMID- 20134849
TI  - Refractive Index of Nd:CaF(2) and Some Nd Doped Glasses as a Function of
      Wavelength, % Neodymium, and Temperature.
AB  - Though the index of refraction of synthetic calcium fluoride has been determined,
      little data exist on neodymium doped calcium fluoride. Measurements of the index
      of refraction of synthetic calcium fluoride doped with 0.001, 0.01, 0.1, 5, 1,
      and 10 mol % neodymium at 16 wavelengths from 4358.35 A to and including 6678.15
      A at 25 degrees C have been made. Most values are believed accurate to +/-3 x 10(
      5). The index of refraction at three wavelengths has been measured at 15 degrees
      C, 25 degrees C, 35 degrees C, and 55 degrees C, and at one wavelength at about
      these same temperatures. Data are also included on a series of five neodymium
      doped glasses.

PMID- 20134851
TI  - Laser Doppler velocimeter as an optoelectronic data processing system.
AB  - Using Fourier optics, the conditions of the laser Doppler velocimeter (LDV)
      optimization in relation to the scattering center size, laser parameters, and
      photoreceiver aperture are found. The measurement errors are estimated for
      average and instantaneous velocities with regard to the statistics of the
      scatterers. The compensating scheme, which eliminates a low-frequency component
      of the signal and laser noise, is described. The results of its experimental
      applications are given.

PMID- 20134852
TI  - Estimating the refractive error in optical measurements of transport phenomena.
AB  - Approximate methods for calculating the error introduced by the deflection of the
      light beam or refractive error in schlieren, shadowgraph, interferometric, and
      holographic measurements of transport phenomena are investigated. Relative error
      is reported for the well-known correction parabola and paraxial approximations as
      well as for a new first-order approximation in both a linear and nonlinear
      refractive index field. The first-order approximation is exact in a linear field
      but is in about the same error as the other approximations in the nonlinear field
      of a boundary layer. In many cases, actual optical data can be corrected for
      refractive errors by using the results presented.

PMID- 20134853
TI  - Measurement of the Velocity of Blood Flow (in vivo) Using a Fiber Optic Catheter
      and Optical Mixing Spectroscopy.
AB  - We have measured the velocity of blood flow in the femoral vein of a rabbit by
      detecting the Doppler shift of laser light introduced into the vein by means of a
      fiber optic catheter. A 0.5-mm diam optical monofiber inserted in the vein
      transmits both the incident light and collects the light scattered from the
      moving erythrocytes. The spectrum of heterodyne beat notes between the local
      oscillator, which originates at the end of the fiber, and the scattered light are
      measured using optical mixing spectroscopy.

PMID- 20134854
TI  - Diffraction losses associated with tungsten lamps in in absolute radiometry.
AB  - The diffraction losses associated with absolute radiometers were calculated for
      the case where the source is a tungsten lamp used with a long wavelength
      suppressing filter. The calculations were done using Blevin's treatment, which
      assumes a point source and a single diffracting aperture. We have shown that this
      treatment is sufficiently accurate for a typical absolute radiometer
      configuration. The calculations were done for color temperatures in the 1600-3200
      K range for three typical glass filters.

PMID- 20134855
TI  - Broadband acoustooptic deflectors: new results.
AB  - A new broadband acoustooptic (AO) Bragg deflector using acoustic beam steering to
      track the Bragg angle is described. It features, instead of the conventional
      stepped array acoustic grating to produce the steering sound column, a flat
      transducer grating made from a single piezoelectric platelet bonded to the AO
      medium, with the spatially periodic phase variations created by interdigitating
      the electrode configuration. The advantage over the conventional stepped array,
      for deflectors operating at frequencies above 100 MHz, is the ease of fabrication
      of the device, an advantage that far outweighs its somewhat reduced acoustic
      power available for light diffraction. An analysis is presented to show that the
      achievable half-power bandwidth from beam steering deflectors under optimum
      design considerations is over four times the bandwidth of fixed beam deflectors
      having the same transducer dimensions. Experimental results on lead molybdate
      deflectors confirm the predicted fourfold improvement.

PMID- 20134856
TI  - Optical constants of sulfuric Acid; application to the clouds of venus?
AB  - With the purpose of obtaining the real and imaginary parts of the complex
      refractive index N; = n + ik, we have made quantitative measurements of spectral
      transmission and reflection of sulfuric acid solutions in the visible and near
      infrared. On the basis of the results, we have obtained values for n throughout
      the entire region and values of k in the near infrared together with upper limits
      for k in the visible region. These optical constants can be used to interpret the
      results of polarization studies of solar radiation that has been scattered by the
      clouds of Venus. We have Kramers-Kronig phase-shift analysis to obtain values of
      n and k from reflection measurements in the intermediate infrared region (400
      4000 cm(-1)). Our measurements were made at 300 K on sulfuric acid solutions
      having concentrations by weight of 95.6, 84.5, 75, 50, 38, and 25%. If the
      particles in the Venus clouds consist of liquid droplets of sulfuric acid at a
      temperature of 250 K, comparison of existing Venus data with our data suggests
      that the acid concentration is probably higher than 70%. Various possibilities
      are discussed.

PMID- 20134857
TI  - High precision scanning ellipsometer.
AB  - We describe the design, construction, alignment, and calibration of a photometric
      ellipsometer of the rotating-analyzer type. Data are obtained by digital sampling
      of the transmitted flux with an analog-to-digital converter, followed by Fourier
      transforming of the accumulated data with a dedicated minicomputer. With an
      operating mechanical rotation frequency of 74 Hz, a data acquisition cycle
      requires less than 7 msec. The intrinsic precision attainable is high because
      precision is limited only by shot noise or intrinsic source instabilities, even
      when relatively weak continuum lamps are used as light sources. Precision may be
      improved by accumulating the data for consecutive cycles at a fixed wavelength.
      The system allows complex reflectance ratios to be determined as continuous
      functions of wavelength from the near infrared to the near ultraviolet spectral
      range. Data reduction programs can be modified to calculate complex refractive
      index or dielectric function spectra, or film thicknesses and refractive indices,
      as well as the usual ellipsometric parameters tanpsi, cosDelta.

PMID- 20134858
TI  - Improvement of birefringent filters. 2:achromatic waveplates.
AB  - By use of Jones' matrix techniques, nine-element achromatic waveplates are
      developed. These combination plates are achromatic to within 1 degrees throughout
      the visible (3,500-10,000 A). In addition, a two-section general retarder rotator
      is demonstrated. The retardation of the combination is twice the complement of
      the angle between the halves, while the rotation is equal to the angle between
      the halves. For a 90 degrees retardation, the dual five-element combination is
      also achromatic to within 1 degrees throughout the visible.

PMID- 20134859
TI  - Narrowband ultraviolet vapor filter.
AB  - A narrowband optical vapor filter based on the principle of selective specular
      reflection from vapors is described. The device consists of a mercury vapor cell
      with Brewster angle windows that selectively reflects the 2537-A line and
      transmits other radiation. The bandwidth of the device varies from 0.1 A to 1.0 A
      as a function of the mercury vapor pressure. Its signal-to-skirt rejection ratio
      at an acceptance angle of 7 degrees is 28 dB, and its acceptance area is 1 cm(2).
      It is used to perform a spectrochemical analysis of mercury in water and also to
      take a monochromatic photograph of the spatial distribution of excited mercury
      atoms in a flame.

PMID- 20134860
TI  - Null ronchi test for aspherical surfaces: authors' reply to comment.

PMID- 20134861
TI  - Asymptotic behavior of an infinite-strip tilted-mirror resonator.

PMID- 20134862
TI  - Comparative performance of color-measuring instruments: second report; authors'
      reply to comments.

PMID- 20134863
TI  - Applied optics of optics and opticists.

PMID- 20134864
TI  - Patents.
AB  - 3,826,557; 3,826,560; 3,826,562; 3,827,798; 3,827,807; 3,834,817; 3,835,315;

PMID- 20134865
TI  - Nonlinear optical microscope using second harmonic generation.

PMID- 20134866
TI  - Luminosity, throughput, or etendue? Further comments.

PMID- 20134867
TI  - Optical activities in industry.

PMID- 20134868
TI  - Comparative performance of color-measuring instruments: second report, comments.

PMID- 20134869
TI  - 10.6-microm Absorption Dependence on Roughness of UHV-Coated Supersmooth Mirrors.

PMID- 20134870
TI  - Multiple scattering measurements as a function of wavelength by use of a dye
      laser.

PMID- 20134871
TI  - Optical scattering per unit mass of single particles.

PMID- 20134872
TI  - Normalization of elastic lidar returns by use of Raman rotational backscatter.

PMID- 20134874
TI  - Fringe vectors and observed-fringe vectors in hologram interferometry.

PMID- 20134873
TI  - New analytic expressions of photographic characteristic curves.

PMID- 20134875
TI  - Relative phase shift of images reconstructed by phase and amplitude holograms.

PMID- 20134876
TI  - Application of a simple differential interferometer to high current arc
      discharges: erratum.

PMID- 20134877
TI  - Modified laser communications subcarrier technique.

PMID- 20134878
TI  - Potential of composites and coatings for reducing thermal distortion from laser
      windows.

PMID- 20134879
TI  - Null ronchi test for aspherical surfaces: comment.

PMID- 20134880
TI  - Woven fiber optics.
AB  - In this paper we describe how the art of weaving can be applied to fiber optics
      in order to produce precisely controlled reproducible image guides and image
      dissectors. As examples of the types of device for which woven fiber optics are
      applicable, we describe a 3:1 interleaver for use with a cathode-ray tube to
      produce color images, and a high speed alpha numeric output device. The
      techniques of weaving fiber optics are discussed in sufficient detail in order to
      allow for further work. Although, in principle, one might be able to weave glass
      optical fibers, all the work described here made use of plastic optical fibers
      0.25 mm in diameter.

PMID- 20134881
TI  - Calculation of coupling losses between light emitting diodes and low-loss optical
      fibers.
AB  - We have investigated the problem of coupling light emitting diodes to
      contemporary low-loss multimode optical fibers (NA ~ 0.14) for optical
      communications. We have calculated the maximum coupled light power and the
      coupling efficiencies for a disk geometry and a strip geometry with and without a
      lens. In our calculations, we assumed that the homostructure LED has a radiance
      of 30 W/sr cm(2) and requires an electrical power input JV or 2 x 10(4) W/cm(2).
      In the disk geometry without a lens, the maximum coupled light power of 36 microW
      can be achieved. With a lens the LED junction area can be reduced so that the
      coupled light power of 31 microW, which is 0.1% of the input electric power, is
      possible. In the strip geometry with a lens a coupled light power of 260 microW
      is achievable.

PMID- 20134882
TI  - Formation of a Spherical Lens at Optical Fiber Ends with a CO(2) Laser.
AB  - A study was made of the use of a CO(2) laser for producing a hemispherical lens
      at the end of a fiber. When the fiber end is heated to the softening points of
      the material, it tends to become spherical in shape due to surface tension. A one
      dimensional heat conduction model for the fiber can reasonably predict the
      required laser power for a given pulse length to produce lenses on fibers made of
      various kinds of materials. A He-Ne laser beam was coupled into a fiber to
      investigate the properties of the spherical lens. We also observed that such lens
      can couple light from a source into the fiber, can be used for imaging, and can
      focus enough laser intensity for machining various materials.

PMID- 20134883
TI  - Output properties of short-pulse gain-switched lasers.
AB  - A formalism is derived for analyzing the spectral and temporal properties of gain
      switched lasers. The development of the longitudinal mode structure from
      spontaneous emission, limiting linewidths, and over-all spectral characteristics
      are considered in detail; and applications are discussed.

PMID- 20134884
TI  - Stability of optical resonators with an active medium.
AB  - The problem of the stability of the Gaussian modes of an optical resonator of
      large mirror apertures filled with a medium having a gain and index profile is
      considered. Recent results by other investigators are carefully examined in an
      attempt to clarify a discrepancy between them. It is found that the modes of the
      resonator are stable if the gain is highest on the resonator axis. When the gain
      increases with distance from the resonator axis, one can calculate a Gaussian
      eigenmode,:but this mode is unstable in the sense that any deviation from the
      exact physical parameters defining the mode will cause its divergence to an
      infinite spot size.

PMID- 20134885
TI  - Fluorescence determination of low formaldehyde concentrations in air by dye laser
      excitation.
AB  - This paper describes a fluorescence technique for the detection of sub-ppm
      concentrations of formaldehyde in air at atmospheric pressure. The aldehyde is
      excited by a frequency doubled tunable dye laser covering the 320-345-nm
      wavelength range. The fluorescence intensity, measured at right angles through a
      400-nm cutoff filter, is proportional to the formaldehyde concentration in air.
      Interferences by NO(2) and SO(2) are negligible. The detection limit of the
      system is 5 pphm at present, in good agreement with an estimate of the
      fluorescence yield in 1 atm of air. A considerable increase of the sensitivity is
      possible, and the use of this technique for measuring formaldehyde in ambient air
      in the ppb concentration range is projected.

PMID- 20134886
TI  - Heat flow analysis of laser absorption calorimetry.
AB  - The time dependent temperature distribution produced in absorption calorimetry of
      very transparent ir materials with a laser is calculated using finite Fourier
      transforms. he solutions are then applied to obtain a function that yields
      numerical corrections for the constant-temperature assumption used in laser
      calorimetry. The results show that the corrections become significant for large
      diameter samples and when measuring the absorption loss of coatings deposited on
      the surfaces of the bulk material.

PMID- 20134887
TI  - Propagation characteristics of a partially metal-clad optical guide: metal-clad
      optical strip line.
AB  - Experimental investigations of the partially metal-clad optical guide were
      performed. The optical guide consisted of a silicon substrate, an SiO(2) low
      index dielectric layer, an Al(2)O(3) high index dielectric layer, and a partial
      cladding layer of Al. The far-field patterns of the output beam from the second
      prism coupler were consistent with the calculated transverse field distributions
      using the effective index-of-refraction method. The experimental results on the
      coupling angles, confinement at the curved section, and attenuation constants are
      also reported.

PMID- 20134888
TI  - Explicit general eigenvalue solutions for dielectric slab waveguides.
AB  - A formula is developed for dielectric slab waveguides that yields general
      solutions of the TE eigenmode propagation constants as explicit functions of a
      composite independent variable involving the guide layer thickness, operating
      wavelength, and refractive indexes of guide and cladding media. This provides a
      convenient means for circumventing the transcendental eigenvalue equations. The
      maximum error is less than 0.6%. A method for deriving the corresponding TM
      eigenvalues with an accuracy of about 99% or better is shown.

PMID- 20134889
TI  - Electric-field induced harmonic generation as a probe of the focal region of a
      laser beam.
AB  - The amount of optical second harmonic generated in a centrosymmetric medium in
      the presence of a dc electric field depends on a convolution of the optical and
      dc field distributions in space. Thus, measurements of the harmonic generation
      associated with a known dc field distribution gives information on the optical
      field distribution. This method has been used to investigate the focal region of
      a laser beam. It avoids difficulties with resolution and probe damage that arise
      when conventional methods are used near the focus. The detailed data are in
      excellent agreement with results predicted for a pure TEM(oo) laser beam with the
      notable exception that the effective confocal parameter is about a factor of 2
      smaller than that indicated by conventional measurements. We believe this effect
      is associated with the truncation of the laser beam by the intracavity mode
      selecting aperture, and indicates that dc induced second-harmonic .generation
      constitutes a sensitive probe of experimentally interesting mode distortios.

PMID- 20134890
TI  - Nonlinear Longitudinal KTN Modulator.
AB  - The longitudinal quadratic electrooptic effect in the solid solution material
      KTa(x)Nb(1-x)O(3) (KTN) has been investigated. It is shown that the effect is
      optimum for the [110] direction. For this direction the effective longitudinal
      electrooptic coefficient for a stress-free crystal is given by g' = |g(12) -
      g(11) + g(44)|. With this effect half-wave voltages as low as 100 V can be
      achieved in thin plates (<200 microm). It is shown that the paraelectric and
      ferroelectric electrooptic effects in these plates can be described by using the
      Devonshire thermodynamic formalism. In particular the temperature variation of
      the half-wave voltage is derived and comparison with the experimentally observed
      variation shows this to be anomalously large. Expressions are also derived for
      the transfer function of a quadratic modulator in both the biased and unbiased
      states. These expressions are in good agreement with the experimental results.
      Finally, the limitations and applications of the longitudinal KTN modulator are
      described. It is concluded that power dissipation problems limit the operation of
      longitudinal KTN devices to frequencies less than 100 kHz.

PMID- 20134891
TI  - Scan line filters for optical spectral analysis.
AB  - A class of filters is studied for applications in optical spectrum analyzers. The
      output device of the analyzer is a masked vidicon. Consequently the design
      criteria differ from those for filters commonly used in digital data processing,
      radar antenna shading, and conventional apodization. It is shown that crosstalk
      or interlocus interference can be reduced for practical geometries to a level
      about 20-30 dB lower than that of an unshaded aperture.

PMID- 20134892
TI  - Optical interpolation with application to array processing.
AB  - The use of spatial filtering for optical interpolation between sample values of a
      function is studied. Onedimensional interpolation between channels of density or
      area modulated spatial signals is analyzed and the effect of nonzero sample width
      presented. A new bound is given for the error due to the number of samples being
      finite. It is shown how exact optical interpolation of periodic functions may be
      obtained from the samples of only one period by the use of a diffraction grating
      in the frequency plane. An experiment demonstrates the application of
      interpolation to processing signals from a simulated sensor array.

PMID- 20134893
TI  - Novel hybrid optical correlator: theory and optical simulation.
AB  - The inverse transform of the product of two Fourier transform holograms is
      analyzed and shown to contain the correlation of the two images from which the
      holograms were formed. The theory, analysis, and initial experimental
      demonstration of the feasibility of a novel correlation scheme using this
      multiplied Fourier transform hologram system are presented.

PMID- 20134894
TI  - Holographic recording by dye-sensitized photopolymerization of acrylamide.
AB  - The dye-sensitized photopolymerization of acrylamide was investigated in order to
      obtain new holographic recording media that have high diffraction efficiency and
      a long photosensitive life. The characteristics of the photosensitive system,
      containing methylene blue as a photosensitizer and acetylacetone or
      triethanolamine as an initiator, were estimated. In the system containing the
      former initiator, the existence of bases was found to be essential and a 20%
      diffraction efficiency was obtained. In the system containing the latter
      initiator, a diffraction efficiency of up to 65% was obtained and the
      photosensitivity was maintained more than 80 days.

PMID- 20134895
TI  - Rotational Raman interferometric technique to measure gas temperatures.
AB  - The rotational Raman interferogram profile of a gas is shown to provide the basis
      for a sensitive, remote measurement of the gas temperature. The technique is
      illustrated by means of a feasibility study of a laser radar atmospheric
      temperature probe. Errors in the measurement are discussed and suggestions given
      for an improved temperature probe.

PMID- 20134896
TI  - Sky brightness and polarization during the 1973 african eclipse.
AB  - The absolute intensity, color, and polarization of the sky were measured during
      the eclipse of 30 June 1973 in Northern Kenya. Zenith sky radiance during
      totality decreased by a factor of 10(4) from the normal day sky value. The
      distribution of sky intensity with angle on the celestial hemisphere was
      approximately symmetrical about the local zenith, with this point having the
      minimum intensity value. The spectral distribution of zenithal diffuse skylight
      shifted toward the blue during totality, but the horizon reddened. The
      polarization ratio P decreased from a normal day value of 0.45 to 0.04. There is
      evidence that the distribution of polarization ratio is strongly affected by
      variations in surface albedo. The major results are compatible with predictions
      based on a radiative transfer model that considers double-scattering processes
      only.

PMID- 20134897
TI  - Der Einfluss der Szintillation auf den Faktor k der Sonnenfleckenrelativzahl.
AB  - The authors combine their own observations and the results of other-authors in
      order to find the relationship between the factor k of the Wolf numbers and the
      seeing. To a first approximation this relationship has a linear slope.
      Furthermore the factor k depends on the Wolf number. At lower activity the
      factors k are greater and the slope is no longer linear.

PMID- 20134898
TI  - Visibility of distant mountains as a measure of background aerosol pollution.
AB  - A relationship is developed between the visibility of distant mountains seen from
      an aircraft and a level of background aerosol pollution for a model atmosphere.
      It is found that the distance at which Mt. Rainier can be seen on clean-air days,
      which are typical of background aerosol levels, is consistent with the level of
      aerosol light-scattering measurements in other background situations.

PMID- 20134899
TI  - Atmospheric Vision 0.35 microm less, similarlambda less, similar 14 microm.
AB  - A unique analytical description of atmospheric vision in the wavelength range
      from 0.35 microm to 14 microm is presented. The signal-to-noise ratio
      corresponding to the apparent radiance difference at the observation site is used
      as the basic physically limiting magnitude. It establishes a general vision
      formula, Eq. (18). This shows that the contrast, C = (L(1) - L(2))/(L(1) + L(2)),
      contrast degradation, and a contrast threshold C(min) = 1/tau DeltaQ(T) can be
      used for the description of photon-noise limited imaging devices, including the
      influence of path radiance. Koschmieder's theory of atmospheric vision follows as
      a special case, using a constant contrast threshold for the human eye. Thermal
      vision in the atmosphere is discussed, together with the relevant magnitudes for
      the description of photon-noise limited and detector-noise limited imaging
      devices that are to be described by the apparent radiance difference only.
      Finally the problem of defining a characteristic length comparable to the
      meteorological range V(N) is considered, and a wavelengthdependent meteorological
      range Vlambda together with a standard maximum range for a special device V(s) is
      proposed.

PMID- 20134900
TI  - Estimation of the depth of sunlight penetration in the sea for remote sensing.
AB  - The penetration depth of light in the sea is defined for remote sensing purposes
      as the depth above which 90% of the diffusely reflected irradiance (excluding
      specular reflectance) originates. It is demonstrated that for a homogeneous
      ocean, this is the depth at which the downwelling in-water irradiance falls to
      1/e of its value at the surface. Penetration depths as a function of wavelength
      are presented for a variety of water types, and a mean penetration depth z (90)
      for a broadband sensor is defined and applied to the MSS on ERTS-1. The maximum z
      (90) expected for ERTS-l is found to be somewhat less than 20 m.

PMID- 20134901
TI  - Computed relationships between the inherent and apparent optical properties of a
      flat homogeneous ocean.
AB  - Monte Carlo simulations of the transfer of radiation in the ocean are used to
      compute the apparent optical properties of a flat homogeneous ocean as a function
      of the inherent optical properties. The data are used to find general
      relationships between the inherent and apparent optical properties for optical
      depths tau </= 4. The results indicate that the apparent optical properties
      depend on the phase function only through the back scattering probability. It is
      shown that these relations can be used with measurements of the upwelling and
      downwelling irradiance, the beam attenuation coefficient, and the incident
      radiance distribution to determine the absorption coefficient, the scattering
      coefficient, and the backward and forward scattering probabilities.

PMID- 20134902
TI  - Spectral remote sensing of temperature distribution in semitransparent solids
      heated by an external radiation source.
AB  - A spectral remote sensing method for recovering the temperature distribution in
      semitransparent solids from remotely sensed spectral emission data is studied. An
      analytical model that relates the emerging spectral intensity from a plane layer
      of solid heated by an external radiation source to the temperature distribution,
      spectral radiation properties, radiation characteristics of the interfaces of the
      solid, and the source is formulated. The temperature profile is expressed in the
      form of a finite series of Legendre polynomials; and the coefficients are
      obtained using an optimization scheme that, by iteratively solving the
      expressions for emerging intensity, reconstructs the distribution that best fits
      the spectral emission data. The validity and accuracy of the remote sensing
      method is evaluated by comparing the recovered temperature with independent
      measurements in two different experiments; one using surface thermocouples only
      and the other a Mach-Zehnder interferometer. Experimental results are reported
      for PPG clear float glass and Corning Code 7940 fused silica using a Perkin-Elmer
      spectrometer and Barnes Spectralmaster radiometer to measure the emerging
      spectral radiant energy. For clear float glass, the recovered temperatures were a
      maximum of 1.5% higher than those measured with surface thermocouples. For fused
      silica, the linear recovered and interferometrically measured temperature
      profiles agreed well, with the maximum deviation never exceeding approximately 2%
      up to about 1000 K.

PMID- 20134903
TI  - Multicolor imagery from holograms by spatial filtering.
AB  - The recording and reconstruction of a multicolor image from a plane hologram by
      spatial filtering in the Fourier plane are discussed. Conditions under which the
      reconstructed images are free from color crosstalk are described and analyzed.
      Experimental results for confirming the analysis by a two-color reconstruction is
      presented. The spatial filter size and the information recording capability are
      determined from hologram recording parameters. It is found that the resolution
      capability of this method is adequate for many practical applications. Methods
      for recording and reconstruction of multicolor images without an imaging lens are
      also discussed. Many possible applications are suggested.

PMID- 20134904
TI  - Improvement of birefringent filters. 3: effect of errors on wide field elements.
AB  - The properties of nontunable and tunable Lyot wide field elements are examined
      when the components of the elements deviate from their proper values. Special
      emphasis is put on determining what variations cause light to be transmitted at
      the transmission minima. The analysis shows that the nine- and ten-element
      plastic waveplates described in Paper 2 of this series can be used to make a Lyot
      filter that is tunable from 3500 A to 10,000 A.

PMID- 20134905
TI  - Johnson Noise Limited Operation of Photovoltaic InSb Detectors.
AB  - Photovoltaic indium antimonide detectors have been operated at temperatures </=77
      K with sufficiently low background radiation levels that Johnson noise limited
      performance is realized. Under such conditions the noise equivalent power (NEP)
      is completely determined by the detector operating temperature, resistance, and
      quantum efficiency. Optimization of these parameters in the manufacture of
      commercially available detectors has led to 5-mum NEP's as low as 10(-15) W. The
      particular preamplifier is critical to the achievement of Johnson noise limited
      operation and is described in detail.

PMID- 20134906
TI  - Infrared circular dichroism and linear dichroism spectrophotometer.
AB  - An instrument for the measurement of circular dichroism (CD) between 5000 cm(-1)
      and 750 cm(-1) is described. This instrument also can perform high precision
      linear dichroism measurements in the same wavelength range. A germanium
      photoelastic modulator having a large linear and angular aperture is used to vary
      the polarization of monochromatic ir light between left- and right-circularly
      polarized at 8 kHz. This polarization-modulated light traverses the sample and
      falls onto a cooled InSb or HgCdTe detector. Phase-sensitive demodulation yields
      the CD of the sample to a precision of 4 x 10(-6) o.d. units near 3000 cm(-1).
      The instrument has been used to study ir circular dichroism arising from
      molecular vibrations in cholesteric liquid crystals, crystals, and fluids. CD
      arising from low-lying electronic transitions of metal complexes and linear
      dichroism of polymer films have also been studied.

PMID- 20134907
TI  - Fast-Scanning Far-infrared Fabry-Perot Interferometer.
AB  - A scanning Fabry-Perot interferometer for use in the far ir (100 microm < < 2 mm)
      has been developed capable of scanning a free spectral range in a few
      milliseconds. A commercial loudspeaker was used as a drive, and mirrors were
      fabricated from electroformed copper mesh. Primary limitations of the instrument
      were due to vibrations of the interferometer frame.

PMID- 20134908
TI  - Versatile nebular insect-eye fabry-perot spectrograph.
AB  - The design and performance of an insect-eye F.P. spectrograph used on the 249-cm
      Isaac Newton telescope, which can also be converted into a nebular filter camera,
      is presented. This device has several novel features, including a pressure
      controlled optically contacted etalon and an image tube as a detector.

PMID- 20134909
TI  - Submillimeter-wave atmospheric and astrophysical spectroscopy.
AB  - The paper describes the results and methods of work which has been in progress
      during the past five years at the U.K. National Physical Laboratory and Queen
      Mary College, London on the submillimeter spectrum and its application to
      atmospheric and astrophysical problems. The paper begins with descriptions of the
      spectroscopic techniques evolved and used, which provide spectral resolution more
      than half an order of magnitude finer than previously available, particularly at
      the lower frequency end of the range, from 15 cm(-1) to 25 cm(-1). Excellent
      signal-to-noise ratios and reproducibility have been obtained and applied as
      shown in the second part of the paper to both atmospheric studies (chiefly at
      NPL) and astrophysical problems (chiefly at QMC). The former are illustrated with
      aircraft-borne measurements of minor species, such as H(2)O, O(3), HNO(3), and
      other gases, the latter with a consideration of the cosmic background at
      submillimeter wavelengths. A common thread is provided by developments in
      observational and interpretational spectroscopic techniques needed to overcome
      problems peculiar to this region of the spectrum. Our current progress in
      understanding the region and also prospects for future submillimeter spectroscopy
      are each brought into review in this work.

PMID- 20134910
TI  - Two-film reflection polarizers: theory and application.
AB  - An analysis is made of reflection polarizers consisting of two transparent films
      on an absorbing substrate. A method is described for determining the angles of
      incidence at which the reflectance of either component of polarization is
      extinguished. It is demonstrated that polarized light can be obtained over a
      finite range of incidence angles. This is in contrast to a polarizer having a
      single transparent film, where polarization occurs only at a specific angle of
      incidence. At each angle of incidence in the polarizing range, any one of a
      number of discrete thicknesses of the films can be used to obtain polarized
      light; and the procedures for finding these thicknesses are described. Numerical
      application of the theory was made for metallic substrates that range from good
      to intermediate reflectors. The results serve to illustrate most of the
      significant characteristics of two-film polarizers. It was shown that two-film
      systems can yield reasonably high values of the unextinguished component, with
      minimal sensitivity of the extinguished component to off-design conditions.

PMID- 20134911
TI  - Requirements for reflection standards and the measurement of their reflection
      values.
AB  - The standards necessary for transferring the reflection scale must meet certain
      requirements. First, the present paper discusses the question of how far these
      requirements are met by the materials now used for realizing the reflection
      standards. Then the instrumentation is described that was developed in the
      Physikalisch-Technische Bundesanstalt for measuring the spectral radiance factor
      beta(lambda) for the d/O and 45/0 geometries and in principle also for the
      inverse geometries. How these measurements are made so that the values obtained
      for a material standard are related to the perfect reflecting diffuser as the
      primary standard is discussed.

PMID- 20134912
TI  - Influence of longitudinal vibrations on the diffraction images of bright
      incoherent disks.
AB  - The intensity distribution in the images of uniform bright incoherent disks is
      obtained in the presence of longitudinal vibrations by using the Fourier Hankel
      transform method. Results are given in graphical form for disks with various
      diameter values. It is observed that in certain cases the presence of
      longitudinal vibrations completely distorts the object. Hence a detailed analysis
      of image intensity distribution should prove useful to those engaged in
      interpretation of photographs in aerial reconnaissance work.

PMID- 20134913
TI  - Irradiance distribution, resolution, and size estimates in diffraction limited
      imagery of extended circular targets.
AB  - Various aspects of diffraction effects on imagery from distributed sources are
      studied. First the irradiance distribution in the focal plane from distributed,
      uniform, circular sources (disks) for optical systems with various obscuration
      ratios, was computed and presented in tables. A resolution criterion, applicable
      both to point sources and distributed sources, is presented and discussed. The
      criterion is based on an assumption that detection requires a minimum contrast.
      The level of this contrast was selected to be 20%. The criterion is applied to
      the case of two neighboring disks, and the numerical results for resolution are
      tabulated. The problem of size estimate, i.e., apparent diameter of a single disk
      on a uniform background, is treated as a question of locating points the
      irradiance at which is a specified level higher than the background. The real
      (geometric optics) diameter of a source is given in graphs in terms of its
      apparent size.

PMID- 20134914
TI  - MTF of Proximity-Focused Image Tube in Polychromatic Light.
AB  - The effect of different conditions of illumination and the spectral sensitivity
      of the detector on the performance of proximity-focused image tube has been
      evaluated in terms of the polychromatic modulation transfer function. The
      physical efficiencies of sources commonly used in the infrared image conversion
      system have been compared for a Corning glass 2540 glass filter and a GaAs filter
      having antireflection coatings on both sides.

PMID- 20134915
TI  - Noise and Other Artifacts in OTF Derived from Image Scanning.
AB  - Image scanning here means measuring intensity distribution in the image of a
      pinhole or slit target with a moving knife edge or slit, with data recorded
      digitally. With the aid of some established methods for empirically estimating
      noise power spectra, combined with prior knowledge of the spectrum of a dominant
      noise process (usually shot noise of the PM tube), quantitative statistical
      formulae are developed that relate the magnitude of the fluctuating part of the
      answers to the several instrumental parameters that must be chosen in planning a
      measurement: the scan length, scanning speed, choice of target and choice of
      scanner, sampling rate, etc. Another noise mechanism, essentially peculiar to the
      computational method, is also examined briefly. The predictive formulae are
      compared statistically with a mass of experimental data, and it is concluded that
      they do predict, to within better than a factor of 2, the outcome of an actual
      measurement. Some sources of systematic error are also briefly discussed.

PMID- 20134916
TI  - Construction of photolithographic phase gratings using the fourier image effect.
AB  - The blurring effect in printing fine grating patterns on photoresist films can be
      minimized by using the Fourier image effect, which involves the image-forming
      nature of periodic patterns in the Fresnel region. Experiments using gratings
      having lattice constants of 3.8 mum and 10 mum are reported. The effectiveness of
      the Fourier image was confirmed by the evaluation of constructed phase gratings
      using diffraction efficiency measurements and SEM observations of sectional
      views. Effects of partial spatial coherence on the quality of gratings are
      discussed.

PMID- 20134917
TI  - Space reflectors for radar and astronomy.
AB  - A new concept to utilize large flat optical reflecting surfaces in space to
      increase by several orders of magnitude the sensitivity and resolution of earth
      laser radar and astronomy measurements is described. The physical principles on
      which simple structures can maintain the optical reflectance gratings in space
      are derived, and the data processing requirements of the measurements are
      discussed. Space and ground system designs are given for a high resolution earth
      resources laser radar sensor, a synchronous earth and planetary science laser
      radar system, and an astronomy observation system including a variable very long
      compound grating interferometer system.

PMID- 20134918
TI  - Scanning kirkpatrick-baez x-ray telescope to maximize effective area and
      eliminate spurious images; design.
AB  - We consider the design of a Kirkpatrick-Baez grazing-incidence X-ray telescope to
      be used in a scan of the sky and analyze the distribution of both properly
      reflected rays and spurious images over the field of view. To obtain maximum
      effective area over the field of view, it is necessary to increase the spacing
      between plates for a scanning telescope as compared to a pointing telescope.
      Spurious images are necessarily present in this type of lens, but they can be
      eliminated from the field of view by adding properly located baffles or
      collimators. Results of a computer design are presented.

PMID- 20134919
TI  - Effects of object and detector sizes on the spatial frequencies of a one
      dimensionally- scanned optical system.

PMID- 20134920
TI  - Applied optics of optics and opticists.

PMID- 20134921
TI  - Patents.
AB  - 3,815,043; 3,815,044; 3,815,046; 3,815,047; 3,818,372; 3,823,061; 3,824,018;
      3,825,764; 3,825,856; 3,828,126; 3,829,218; 3,829,219.

PMID- 20134922
TI  - Possibility of atmospheric temperature sounding by the solar occultation
      technique.

PMID- 20134923
TI  - Optical activities in industry.

PMID- 20134924
TI  - Meeting reports.

PMID- 20134925
TI  - Rayleigh, the unit for light radiance: comment.

PMID- 20134926
TI  - Determination of refractive index changes in photosensitive polymer films by an
      optical waveguide technique.

PMID- 20134927
TI  - Filtres a reflexion interne totale.

PMID- 20134928
TI  - Binary synthetic holograms: comments.

PMID- 20134929
TI  - Holographic simulation of parabolic mirrors.

PMID- 20134930
TI  - Orthoscopic color holography of 3-d objects.

PMID- 20134931
TI  - Practical Limitation on M-ary Optical Communications Data Rates.

PMID- 20134932
TI  - Integrated Optics: a Report on the 2nd OSA Topical Meeting.
AB  - This report surveys the papers presented at the 2nd OSA Topical Meeting on
      Integrated Optics, which was held 21-24 January 1974 in New Orleans, La.

PMID- 20134933
TI  - Lightguiding in photochromic glasses.
AB  - Lightguiding in ion-exchanged photochromic glass layers is reported. The guides
      were formed by ion exchange of Ag(+) for Na(+) or by outdiffusion of F. Guide
      attenuation was less than 0.2 dB/cm in many cases. The attenuation in the guide
      was varied over a range of Deltaalpha = 30 dB/cm by illuminating the guide with
      (1) uv radiation to darken the guide or order of seconds. (2) visible radiation
      to bleach the guide. Switching times were in the order of seconds.

PMID- 20134934
TI  - Fiber optic sheets of ridged polymer films.
AB  - Fiber optic sheets (10 lines/mm) have been made by a new technique in which a
      monomer is diffused into a ridged polymer film with a higher refractive index and
      then polymerized by gamma-ray irradiation. The diffusion profile was controllable
      from the clad type to the self-focusing type by adjusting the diffusion
      conditions. The attenuation in the polycarbonate light path (n = 1.59), enclosed
      with the chemically fixed methyl acrylate polymer (n = 1.49), was 0.5-0.7 dB/cm
      lambda = 633 nm.

PMID- 20134935
TI  - Modes of a diffraction grating optical resonator.
AB  - An open resonator that consists of a spherical mirror and a reflection grating is
      described. The eigenmodes and eigenvalues are calculated numerically, utilizing
      the Fox and Li iterative method. By proper design of the grating, one may control
      the amount of energy coupled out through the grating's orders while the
      eigenmodes are almost unaffected.

PMID- 20134936
TI  - Photopolymer material for holography.
AB  - An experimental Du Pont holographic photopolymer material produces an index
      modulation in excess of 10(-2) utilizing a diffusion mechanism. Optimum exposure
      in air is typically 30 mJ/cm(2) , in nitrogen 3 mJ/cm(2). Composition, beam
      ratio, and exposure power all affect the index modulation. This, combined with
      thickness variations, permits diffraction efficiency to be preadjusted for a
      variety of desired angular responses and spatial frequencies. The material can be
      easily overmodulated according to Kogelnik's phase grating theory. No wet
      processing is required. After total polymerization, storage at 100 degrees C, -60
      degrees C, and under water does not significantly affect the diffraction
      efficiency. Image-object superposition is exact for real-time holography.
      Excellent copies of silver halide holograms with four times the original
      efficiency have been made. Grating devices with tailored peak or flat wavelength
      response can be constructed.

PMID- 20134937
TI  - Pulse holography of uniformly moving objects.
AB  - Holography of a uniformly moving object with a pulse laser is analyzed
      theoretically, and the irradiance in the reconstructed image is calculated. The
      image irradiance is attenuated due to object motion and due to finite path
      difference between the reference and the object beams. The attenuating factor due
      to object motion, which is the more serious one, can be calculated either in
      terms of a varying path difference between the reference and the object beams or
      in terms of a shift in object frequency due to Doppler effect. If the reference
      frequency is shifted so as to make it equal to the Doppler-shifted object
      frequency, the effect of object motion on the reconstructed irradiance can be
      canceled.

PMID- 20134938
TI  - Edge diffraction of a convergent wave.
AB  - Closed-form solutions have been derived for the diffraction patterns at the focal
      plane of (1) a convergent wave of unit amplitude illuminating a segment of a
      circular aperture and (2) a convergent wave of Gaussian amplitude diffracted by
      an infinite edge. Photographs showing the main features of these edge transform
      patterns are presented together with computer-generated graphs.

PMID- 20134939
TI  - Tilted-reference-beam lateral shearing interferometer utilizing carrier-frequency
      photography.
AB  - Double-exposure carrier-frequency photography where the grating is rotated
      between exposures is used for observing phase objects. The resulting
      interferogram is similar to those obtained from interferometers using a tilted
      reference beam. Positive and negative gradients of the phase variation can be
      distinguished. Furthermore, it is shown that the image of a grating in carrier
      frequency photography can be achieved by using an image-forming lens or by using
      the self-imaging property of the grating.

PMID- 20134940
TI  - Speckle-shearing interferometric technique: a full-field strain gauge.
AB  - An improved speckle-shearing interferometric method is presented that allows
      simultaneous determination of derivatives of surface displacements of a structure
      with respect to four different directions. The technique relaxes several
      limitations associated with conventional interferometry and thus is adaptable to
      nonlaboratory environments. The relevant theory is presented, and the method
      demonstrated by determining spatial derivatives of in-plane and out-of-plane
      displacements of statically loaded and vibrated structures.

PMID- 20134941
TI  - Spherical aberration measurement with shearing interferometer using fourier
      imaging and moire method.
AB  - The experimental and quantitative study of the measurement of the lateral
      spherical aberration with the shearing interferometer using Fourier imaging and
      the moire method is given. When the aberration of a camera lens with small
      f/number(1.7) is measured with an optical arrangement employing the spherical
      wavefront as a reference at the observation plane, the distortion correction of
      the obtained fringes is necessary. However, the fringe pattern directly
      illustrating the lateral spherical aberration can be obtained by the proposed
      optical arrangement using the plane reference wavefront, without correcting the
      fringe distortion.

PMID- 20134942
TI  - Pulsed HF Laser Holographic Interferometry.
AB  - Two-dimensional holographic interferometry has been accomplished at wavelengths
      near 3 microm. The source is a pulsed hydrogen fluoride oscillator-amplifier
      system. Transverse excitation is achieved with a fast bank discharging into a
      simple electrode configuration. The spatial detector is a thin film of bismuth,
      exposed by local evaporation by a single line of the HF laser emission spectrum.
      Double exposure interferograms covering areas up to ~10 cm(2) in the object plane
      have been obtained with single-line laser energies of less than a joule.

PMID- 20134943
TI  - Mach-zehnder interferometer data reduction method for refractively inhomogeneous
      test objects.
AB  - Refractively inhomogeneous, cylindrically symmetric test objects, when placed in
      a Mach-Zehnder interferometer, cause fringe shifts that cannot be reduced with an
      inverted Abel integral equation to accurately determine the internal index of
      refraction distribution. Optical principles have been used to formulate an
      appropriate method of data reduction that is amenable to reasonably simple
      numerical procedures. Two analytic examples are presented that demonstrate that
      under the above conditions the deduced refractivity distribution can be
      dramatically incorrect, both qualitatively and quantitatively, if an inverted
      Abel equation is used to reduce the fringe-shift data.

PMID- 20134944
TI  - Effect of dispersion on the reflection and transmission extrema from a monolayer.
AB  - The use of the quarter-wave optical thickness concept in the design of certain
      types of multilayer optical filters, or in the thickness determination of optical
      thickness of monolayers from transmission or reflection data, can present
      appreciable errors if dispersion is present in the layer optical constants.
      Moderate amounts of dispersion can cause significant shifts in the location of
      the global reflection or transmission extrema from what would be predicted using
      simple optical thickness considerations. Examples, including the use of measured
      index of refraction values for CeO(2), are presented.

PMID- 20134945
TI  - Selection of cw Mode-Locked Laser Pulses.
AB  - A compact device capable of selecting pulses from a cw mode-locked pulse train is
      described. A single pulse, a repetitive train of pulses, or a random pulse may be
      selected. Tests results are given.

PMID- 20134946
TI  - Precision Beam Splitters for CO(2) Lasers.
AB  - Beam splitters for 10-mum lasers are discussed and then applied to the precision
      measurement of high average powers. In particular, beam splitter stability has
      been investigated in various materials over the 20-600-W power range with power
      densities up to 1 kW/cm(2). The absolute beam splitter ratios are given along
      with the achieved measurement precisions. The semiconductors investigated were
      GaAs, CdTe, and ZnSe in addition to one alkali-halide KCl. Standard deviations
      for the beam splitter ratios of 1% over the power range were typical. Absolute
      ratios agree with the predictions from Fresnel's equations to 1% or better. The
      best measurement was made on ZnSe when a standard deviation of 0.4% was obtained
      for the measurement of a ratio that agreed with a calculation from Fresnel's
      equations to better than 0.5%.

PMID- 20134947
TI  - Narrow-Bandwidth Tunable Infrared Difference-Frequency Generation at High
      Repetition Rates in LilO(3).
AB  - Difference-frequency generation was studied in LiIO(3) with a narrow-bandwidth
      tunable dye laser pumped at high pulse-repetition rates by a frequency-doubled
      Nd:YAG laser. Tunable infrared radiation of 0.1, cm(-1) bandwidth was generated
      from 1.25 mum to 1.60 mum and from 3.40 mum to 5.65 mum by mixing rhodamine B dye
      laser cavity radiation with the 1.064-mum or 532-nm output of the Nd:YAG laser.

PMID- 20134948
TI  - Laser detection of photoinjected images.
AB  - An image detection technique using remote ir laser readout of optically injected
      carriers is described. The image target consists of homogeneous, contact-free
      semiconductor surfaces. The equations governing sensitivity, response time, and
      resolution are presented. Experimental results and practical configurations are
      described.

PMID- 20134949
TI  - Speckle noise reduction by random phase shifters.
AB  - Experimental results are given that show that a random phase shifter (RPS) is
      effective in reducing speckle noise caused by optical defects in coherent imaging
      systems, including holographic imaging systems. Here the RPS is composed of many
      tiny transparent blocks, each of which gives a definite phase shift such as O or
      pi to the transmitting light; and the distribution of the phase shift is two
      dimensionally random. The optical defects are scattering centers such as
      scratches or dust on lenses or on the hologram medium in the case of holographic
      imaging systems.

PMID- 20134950
TI  - Three-Frequency Nonlinear Heterodyne Detection. 1: cw Radar and Analog
      Communications.
AB  - Though heterodyne detection provides a valuable technique for detecting small
      signals, the conventional system has several inherent disadvantages. In
      applications such as communications and radar, obtaining a reasonably high signal
      to-noise ratio (SNR) requires (1) a good knowledge of the velocity of the
      transmitter or target, (2) a stable yet tunable local oscillator, and (3) a
      target or source that presents a minimum of frequency broadening. These
      conditions are frequently not adhered to by real systems, particularly in the ir
      and optical, giving rise to detection capabilities far below optimum.
      Calculations are presented for the use and operation of a three-frequency
      nonlinear heterodyne system that eliminates many of the stringent conditions
      required for conventional heterodyne detection, while maintaining its near-ideal
      SNR. The technique, which is similar in principle to heterodyne radiometry, makes
      use of a two-frequency transmitter and a nonlinear second detector and is
      particularly useful for signal acquisition; for signals of unknown Doppler shift,
      in fact, performance is generally superior to that of the conventional system.
      Although primary emphasis is on the ir and optical because of the large Doppler
      shifts encountered there, application of the principle in the microwave and
      radiowave is also discussed. For cw radar and analog communications, the SNR,
      power spectral density (PSD), and minimum detectable power (MDP) are obtained and
      compared with the standard configuration. Both sinewave and Gaussian input
      signals are treated. A variety of specific cases are discussed including the
      optimum performance case, the typical radar case, and the AM and FM
      communications case. Evaluation of the technique for pulsed radar and digital
      communications applications (both in the absence and in the presence of the
      lognormal atmospheric channel) is reserved for Part 2 of this paper [Appl. Opt.
      14, 680 (1975)].

PMID- 20134951
TI  - Three-frequency nonlinear heterodyne detection. 2: digital communications and
      pulsed radar.
AB  - Part 1 of this paper [Appl. Opt. 14, 666 (1975)] dealt with the cw radar and
      analog communications uses of three-frequency nonlinear heterodyne detection. In
      this paper, we evaluate the technique for a number of specific pulsed radar and
      digital communications applications. Both the vacuum channel and the lognormal
      turbulent atmospheric channel are considered. It is found that the advantages of
      the technique in the pulsed/digital system are similar to those obtained in the
      cw/analog system. Computer generated error probability curves as a function of
      the input signal-to-noise ratio are presented for a variety of binary receiver
      parameters and configurations and for various levels of atmospheric turbulence.
      Orthogonal and nonorthogonal signaling schemes, as well as dependent and
      independent fading, are considered. When Doppler information is poor, performance
      is generally superior to that of the conventional heterodyne system.

PMID- 20134952
TI  - Coherent Detection Signal-to-Noise.
AB  - General equations are derived for the signal-to-noise ratio of a coherent
      (heterodyne) receiver in terms of the distribution functions of the signal and
      local oscillator fields and the size and shape of the detector. The optimum local
      oscillator field distribution is identical to the signal field distribution over
      the detector surface. The special case of an Airy function signal distribution
      and a uniform local oscillator distribution on a circular detector has an optimum
      detector radius 72% of the radius of the Airy disk, which gives a signal- to
      noise ratio of 0.72 etaP(s)/hnuB(i.f.).

PMID- 20134953
TI  - Single electron recording by self-scanned diode arrays.
AB  - A unique multichannel photoelectron counting system can be made by using self
      scanning semiconductor arrays in the electron bombardment induced mode provided
      the SNR in the self-scanning arrays permits the detection of single electrons. To
      investigate this in an experimental program, self-scanning light sensitive diode
      arrays were subjected to electron bombardment. In one experiment, a radioactive
      source Ni(63) was used to show that the 128 element (Reticon RL128L) self-scanned
      linear diode arrays were responsive to electrons, and good agreement could be
      derived between the high energy portion of the incident and -measured fluxes. In
      another experiment using an electron accelerator and 42-keV electrons, clear
      resolution of the pulse distribution peaks was obtained due to single, double,
      and triple incidences of electrons. The relative heights of the observed peaks
      obeyed a Poisson distribution as expected for random electron incidence. The
      incorporation of this device into a photoelectronic tube will result in a self
      scanned photoelectronic detector closely approaching the theoretical performance
      limit.

PMID- 20134954
TI  - Laser Induced Damage in Optical Materials: 6th ASTM Symposium.
AB  - The Sixth ASTM-ONR-NBS Symposium on Laser Induced Damage in Optical Materials was
      held at the National Bureau of Standards in Boulder, Colorado on 22-23 May 1974.
      Over 150 attendees at the Symposium heard thirty-one papers on topics relating to
      laser induced damage in crystalline and nonlinear optical materials, at
      dielectric surfaces, and in thin film coatings as well as discussions of damage
      problems in the ir region due both to cw and pulsed irradiation. In addition,
      several reports on the theoretical analysis of laser-materials interaction
      relative to the damage progress were given, along with tabulations of fundamental
      materials properties of importance in evaluation of optical material response to
      high-power laser radiation. Attention was given to high-power laser system design
      considerations that relate to improved system performance and reliability when
      various damage mechanisms are operable in such systems. A workshop on the
      machining of optics was held, and nine papers on various facets of the topic were
      presented dealing with machining procedures, surface characterization of machined
      elements, coating of machined components, and the polishing and damage resistance
      of polished, coated, and bare metal reflectors.

PMID- 20134955
TI  - Effect of temperature gradients on the wave aberration in athermal optical
      glasses.
AB  - Temperature gradients that are caused by partial heating in optical elements may
      result in wave aberrations. The athermal glasses developed within the past two
      years exhibit considerably reduced thermal wave aberrations compared to the
      classical optical glasses. Evidence is given that the total wave aberration is
      due not only to the change of optical path DeltaW(Gamma) computed from a, n, and
      dn/dT, but also that, upon the occurrence of thermal stresses, an additional wave
      aberration DeltaW(s) must be taken into consideration.

PMID- 20134956
TI  - Calorimeter to Measure the 10.6-microm Absorption of Metal Substrate Mirrors.
AB  - We have designed, constructed, and tested an instrument to calorimetrically
      measure the 10.6-microm absorption a of high reflectivity metal-substrate
      mirrors. Optical, electrical, and thermal design considerations will be
      discussed. The technique of absorption measurement, including the in situ heat
      capacities, the reflected laser light to an accuracy of +/-4%, and the simplified
      data reduction technique will be discussed. From our error analysis we conclude
      that our accuracy is +/-0.1alpha and has a precision of 0.0005. Comparative
      measurements on the same mirrors by different reflectivity and absorption devices
      and extensive absorption data on state-of-the-art 10.6-microm metal-substrate
      mirrors will be presented. The best absorption that we have measured is 0.0010
      for a gold-coated multidielectric enhanced mirror.

PMID- 20134957
TI  - Assessment of the ultraviolet range of artificial light sources for the best fit
      to standard illuminant d65.
AB  - For color matching and color measurement of fluorescent samples, artificial light
      sources are required that, have an irradiance distribution of maximum possible
      fit to that of the standard illuminant D65, even in the ultraviolet-wavelength
      range. Expanding an earlier study, calculations are made as to how much more
      information is obtained when the assessment of the uv range is carried out with
      not just one, but a larger number of fluorescent samples. Thirty-seven irradiance
      distributions are tested with thirty-one hypothetical samples. It seems most
      practical to use three samples for the assessment.

PMID- 20134958
TI  - Response calculations for light-scattering aerosol particle counters.
AB  - Response calculations for five commercial light-scattering aerosol particle
      counters have been carried out that take into account the emissive power of the
      light source, the spectral sensitivity of the phototube, and the specific
      geometrical factors for each instrument. Earlier calculations had been published
      for two of these instruments, but these had not considered each of these factors
      appropriately. The results indicate a strong dependence of response upon both the
      real and imaginary part of the refractive index and, for a given refractive index
      a multivalued response in the submicrometer range for three of the five
      instruments.

PMID- 20134959
TI  - Homodyne electrophoretic light scattering of polystyrene spheres by laser cross
      beam intensity correlation.
AB  - Homodyne light fluctuation spectroscopy is combined with an electrophoresis
      apparatus to provide a technique that rapidly measures electrophoretic mobilities
      of charged particles suspended in a liquid medium. Two parallel laser beams,
      polarized in the same direction, are focused into a scattering cell by a
      cylindrical lens. The laser beams interfere at the focal point of the lens to
      produce a fringe intensity profile. As scattering particles are driven through
      the fringes, the scattered light intensity is modulated. This modulation is
      detected by digital autocorrelation of photoelectron pulses from a
      photomultiplier. With this technique the electrophoretic mobility of 1-micro diam
      monodisperse polystyrene spheres was determined to be 4.6 +/- 0.2
      (micro/sec)/(V/cm) in water.

PMID- 20134960
TI  - White Light Coronagraph in OSO-7.
AB  - A small, externally occulted Lyot-type coronagraph, designed for use in the
      seventh unmanned Orbiting Solar Observatory (OSO-7), is described. Optical
      configuration, suppression of stray light, SEC vidicon detector, and data system
      are discussed, as well as integration of the instrument into the spacecraft and
      operation in orbit. Orbital operation produced daily images of the white light
      corona, from 2.8 to 10 solar radii, at least once per day for 2(3/4) yr. The
      first records of white light coronal transient events were obtained, and the
      corona was shown to be constantly changing.

PMID- 20134961
TI  - Correction for errors in optical pulsed range measurements.
AB  - Corrections for the errors that occur in pulsed optical ranging such as satellite
      ranging are generally analyzed. It is shown that corrections for range errors can
      be described as a linear combination of the atmospheric correction, the spatial
      correction, and the corrections for the errors in electrical circuits. A method
      for the calibration and the correction of observed distances by using a standard
      target is presented. Particularly in local ranging, corrected distances are
      easily calculated by two standard targets, even if the atmospheric refractive
      index and the accuracy of the time base of the counter are unknown. Ranging
      experiments on earth from 100 m to 10 km were made with the laser system. The
      corrected distances, using two standard targets, agree well with distances
      measured accurately by a Geodimeter within the pulse width of the laser, 50 nsec
      (7.5 m), and the resolution of the time interval counter, 10 nsec (1.5 m).

PMID- 20134962
TI  - High frequency polarization modulation method for measuring birefringence.
AB  - A high frequency modulation method utilizing a photoelastic polarization
      modulator for the measurement of optical birefringence is described and
      discussed. Although the apparatus has the high sensitivity required to measure
      very small retardations, the accurate measurement of larger retardations is
      emphasized and a particularly simple null detection technique for such
      measurements is described. Results obtained for some common uniaxial crystals are
      presented and compared with previously obtained results.

PMID- 20134963
TI  - High frequency polarization modulation method for measuring optical rotation.
AB  - A high frequency photoelastic modulator is used to measure optical rotation. Its
      application for rotations of different orders of magnitude is described and
      assessed. The method has high sensitivity and permits rapid, accurate, and
      continuous measurements. Illustrative results are given for crystals having
      either natural or magnetically induced optical activity.

PMID- 20134964
TI  - Tilt tunable ultra narrow-band filters for high resolution infrared photometry.
AB  - The design and operating characteristics of several recently fabricated solid
      spaced Fabry-Perot interference filters having bandwidths from 0.3 A to 8 A in
      the 1-5-microm ir wavelength range are discussed. The 10(4) achievable resolving
      power of these devices, particularly at the higher wavelengths, represents
      several orders of magnitude improvement over conventional ir filters, and the
      implications of this very high resolution along with the tilt-tuning properties
      of narrow-band filters are discussed in relation to atmospheric remote sensing.

PMID- 20134965
TI  - Simplified recording microspectrophotometer.
AB  - Most of the recording microspectrophotometers described to date are laboratory
      built instruments utilizing a carefully designed optical train and dynode
      feedback to the photomultiplier tube. We describe in this report a simplified
      recording microspectrophotometer designed to eliminate the above two
      requirements. In addition, improvements in electronic circuitry due to the use of
      solid-state operational amplifiers are described. A capability for use in visual
      pigment studies is demonstrated.

PMID- 20134966
TI  - Spectral analysis and cross-correlation techniques for photon counting
      measurements on fluid flows.
AB  - Photon counting techniques for the measurement of turbulent fluid flows are
      analyzed, and it is shown that considerable errors can result if conventional
      Fourier methods are used to transform count correlation records from LDV systems
      onto the frequency domain. Two alternative schemes are presented that overcome
      this difficulty. The first involves the use of high resolution spectral
      techniques to transform count autocorrelation records, and the second makes use
      of the count cross-correlation between signals from two detectors. A theoretical
      analysis is presented for the count cross-correlation process, and experiments in
      air flow show turbulence levels predicted by the two methods to be in close
      agreement.

PMID- 20134967
TI  - Multiplexed dispersive spectrometers using reduced background infrared detectors.
      Comment 2.

PMID- 20134969
TI  - Theological optics.

PMID- 20134968
TI  - Patents.
AB  - 3,704,932; 3,706,495; 3,708,222; 3,796,493; 3,796,498; 3,814,505; 3,814,510;
      3,817,599; 3,816,735; 3,817,600; 3,817,602; 3,818,125; 3,819,253; 3,819,256;
      3,820,876; 3,820,897; 3,821,466; 3,821,551; 3,822,087; 3,822,931; 3,825,346;
      3,826,992; 3,827,062; 3,827,781; 3,827,786; 3,827,793; 3,828,187; 3,829,198;
      3,830,558; 3,830,559; 3,830,571; 3,832,028; 3,832,029; 3,832,030; 3,833,284;
      3,833,286; 3,833,290; 3,833,810.

PMID- 20134970
TI  - Space Spangs-an Error. 2.

PMID- 20134971
TI  - Each: a system of units.

PMID- 20134972
TI  - Meeting reports.

PMID- 20134973
TI  - Optical activities in industry.

PMID- 20134974
TI  - Long-term uplink irradiance statistics from reciprocity.

PMID- 20134975
TI  - Improved method for azimuthal alignment in ellipsometry.

PMID- 20134976
TI  - Kubelka-munk optical coefficients for a barium sulfate white reflectance
      standard.

PMID- 20134977
TI  - Orientation of crystals by extinction between crossed linear polarizers.

PMID- 20134978
TI  - Multiplexed dispersive spectrometers using reduced background infrared detectors:
      comment 1.

PMID- 20134979
TI  - Diffraction grating use to reject fluorescence from a tunable dye laser.

PMID- 20134980
TI  - Polarization Considerations in the Operation of a Two-Dimensional TeO(2) Abnormal
      Bragg Deflector.

PMID- 20134981
TI  - Refractive index profile of a graded index fiber: measurement by a reflection
      method.

PMID- 20134983
TI  - Optical fiber vacuum chuck.

PMID- 20134982
TI  - Eccentric coupler for optical fibers: a simplified version.

PMID- 20134984
TI  - Spectral Sensitivity and Linearity of Shipley AZ-1350J Photoresist.

PMID- 20134985
TI  - Spatial frequency response of thermoplastic films.

PMID- 20134986
TI  - Optical information channels: page-accessed and bit-accessed.

PMID- 20134987
TI  - Vertical Distribution of NO, NO(2), and HNO(3) as Derived from Stratospheric
      Absorption Infrared Spectra.
AB  - This paper is devoted to the results concerning NO, NO(2), and HNO(3) obtained
      during airborne experiments performed in June-July 1973 on Concorde 001. The
      altitude of flight was about 16 km. Results concerning NO are, within the
      accuracy of measurement, in agreement with results of a previousspectrometric
      balloonborne experiment conducted jointly by IASB and ONERA (14 May 1973). Nitric
      oxide is concentrated in stratospheric layers clearly above the flight altitude.
      Integrated amount of NO along the optical path is (4 +/- 1.5) x 10(16) mol cm(-2)
      for a solar elevation varying from +2 degrees above the horizontal plane to -1
      degrees . A value of 6 x 10(8) mol cm(-3) may be given as an upper limit for the
      local concentration at the flight altitude. Thereis no significant difference in
      the integrated amount observed at sunset and sunrise. Measured value of NO(2)
      local concentration at 15.5 km is (1.1 +/- 0.2) x 10(9) mol cm(-3), in sunset
      conditions. This value is not greatly modified between 15 km and 30 km. Measured
      value of HNO(3). This value increases with altitude between 15 km and 20 km. The
      local concentration is maximum at 20 km. The measured value is (2 +/- 1) x 10(10)
      mol cm(-3) at 20 km. It seems that local concentration decreases rapidly above 20
      km.

PMID- 20134988
TI  - Atmospheric distortions in a retroreflected laser signal.
AB  - This paper presents and analyzes a model for the instantaneous received field
      that has been transmitted from a laser and then retroreflected from a corner
      cube, all in the presence of atmospheric turbulence and attenuation. The
      characteristics of this field are examined as a function of distance from the
      axis of the transmitted laser beam, and the merits of using shared optics
      (coaxial transmitter/receiver) from geometric and atmospheric considerations are
      examined. in particular, it is shown that angle-of-arrival (AOA) fluctuations
      induced by turbulence would be self-corrected in a retrosystem for a shared
      optics configuration only if the transceiver and retroreflector are in each
      other's effective near fields or are separated by less than a self-correction
      range as defined in the text. The results are shown to be in agreement with
      recent experimental observations.

PMID- 20134989
TI  - Atmospheric turbulence parameters from visual resolution.
AB  - Direct visual observations of image blurring by atmospheric turbulence are used
      to obtain line averages of the refractive index structure function coefficient
      C(n)(2) along lines of sight in the lower atmosphere. Good agreement with
      meteorological point measurements is obtained both above a dry land surface,
      where temperature fluctuations cause most of the image degradation, and above a
      pond, where humidity fluctuations are also important. No optical saturation
      effects are found, and a simplified formula for determining longexposure,
      limiting-resolution angles is verified.

PMID- 20134990
TI  - Long-path monitoring of atmospheric carbon monoxide with a tunable diode laser
      system.
AB  - Long-path measurements of carbon monoxide in the atmosphere are described. The
      technique of resonance absorption was used in which the wavelength of radiation
      from a PbS(0.82)MbSe(0.18) semiconductor diode laser was tuned into coincidence
      with an absorption line of CO in its fundamental band around 4.7 microm. By
      employing rapid frequency modulation of the laser emission to overcome
      atmospheric turbulence effects, it was possible to achieve a minimum detectable
      concentration of 5 parts per billion over a 0.61-km path. Continuous around-the
      clock monitoring was also performed and permitted increases in the ambient CO
      level due to commuter traffic to be observed.

PMID- 20134991
TI  - Numerical solutions in remote sensing.
AB  - Several aspects of the behavior of Fredholm integral equations are examined in
      this paper. It is shown that collocation methods are better in general than least
      squares methods in linear approaches. The amplification of random noise inherent
      to the numerical inversion of the equation puts an upper limit to the information
      content of an ill-conditioned system. An estimation based on the magnitude of SNR
      is proposed for a system that lacks statistical information to determine the
      information content and to reconstruct the solution profile. To reduce the
      numerical instability of matrix inversion, some specific kernel transformations
      are discussed. Illustrative examples are given and compared to results of other
      approaches. An alternative linear approach that orthonormalizes the kernels-is
      also proposed. The linear approach was then employed in solving the radiative
      transfer equation with temperature-independent kernels. The necessary variable
      separation in linear inversions was examined. Iteration refinement was found
      necessary to accommodate the strong nonlinearity of high temperature sensing.

PMID- 20134992
TI  - Optical surface roughness determination using speckle correlation technique.
AB  - Two speckle patterns produced from the same rough surface by two different
      illuminations are correlated. The correlation depends on the surface roughness.
      The two illuminations were obtained here by varying the angle of incidence of a
      coherent plane wave on the surface. The speckle patterns are recorded on the same
      film by double exposure. By placing this film in a convergent laser beam, Young
      fringes are observed in the Fourier plane. The correlation of the speckle
      patterns is obtained by measuring the visibility of the fringes. The theoretical
      calculations have been performed for a normally distributed surface. The
      experimental results are in good agreement with theory.

PMID- 20134993
TI  - Practical speckle interferometry for measuring in-plane deformation.
AB  - Speckle interferometry involves making a high resolution double-exposure
      photograph of an object that is illuminated with coherent light. When observed in
      a Fourier optical data processor, fringes are observed that are indicative of the
      changes, such as displacements, occurring in the body between exposures.
      Sensitivity of the measurement is variable and may be chosen after the data are
      recorded. A simple calibration procedure is described and its use in measuring in
      plane displacements in deformable solids is demonstrated. Also given are some
      limitations on the range of sensitivity that can be effectively utilized with
      holographic films, simple procedures, and a small laser.

PMID- 20134994
TI  - Interferometric recording of the deflections of towers and telescopes.
AB  - Wind generates vibrations in towers and in telescopes placed in the open air.
      Interferometers for measuring these vibrations were developed. Applications to
      scale models of a telescope led to improvements of the telescope design. An
      optoelectronic system using three photocells for scanning the interferometer
      fringes allows the application of an inexpensive laser with several longitudinal
      modes as a light source for the interferometers.

PMID- 20134995
TI  - New 10-microm Infrared Interferometer and Its Applications.
AB  - A new interferometer has been developed which can be used both for analyzing the
      homogeneity of ir materials and for inspecting the waveform emerging from an
      optical system. This new type of interferometer utilizes a diffraction grating as
      a beam divider and further permits an important variation in the fringe contrast
      to be obtained for a given blaze angle by the variation of the efficacity of the
      grating with the orientation of the plane of polarization. This improvement
      permits the compensation of photometric losses due to either an absorbing
      material or a highly reflecting material that may be under test. By this way it
      is possible to evaluate all materials within a 10-100% transmission range. This
      interferometer functions at 10.6 mu ;m. Results obtained are detailed herein.

PMID- 20134996
TI  - Flow tracing fidelity of scattering aerosol in laser Doppler velocimetry.
AB  - An experimental method for the determination of the flow-tracing fidelity of a
      scattering aerosol used in laser Doppler velocimeters was developed with
      particular reference to the subsonic turbulence measurements. The method employs
      the measurement of the dynamic response of a flow-seeding aerosol excited by
      acoustic waves. The amplitude and frequency of excitation were controlled in
      order to simulate the corresponding values of fluid turbulence components.
      Experimental results are presented on the dynamic response of aerosols over the
      size range from 0.1 microm to 2.0 microm in diam and over the frequency range 100
      Hz to 100 kHz. It was observed that unit-density spherical scatterers with
      diameters of 0.2 mmicrom followed subsonic air turbulence frequency components up
      to 100 kHz with 98% fidelity.

PMID- 20134997
TI  - Laser Doppler velocimetry using a superheterodyne spectrum analyzer.
AB  - We present a superheterodyne optical spectrum analyzer where the frequency of the
      local oscillator changes linearly in time via an acoustooptic modulator. With
      this device we analyze the power spectrum of the light scattered by a rotating
      cylinder; a theoretical expression of the power spectrum shows that the spectrum
      width depends essentially on three different parameters: the angular velocity of
      the cylinder, the scattering angles, and the apparent linear dimensions of the
      illuminated area.

PMID- 20134998
TI  - Physical constraints associated with the development of a laser based on
      electrochemiluminescence.
AB  - A theoretical study of the possibility of attaining laser action from an
      electrochemiluminescence system has been undertaken. A simple model has been
      found that is capable of predicting the width of the excited state creation zone
      in terms of the peak excited state concentration. This relation reveals that
      diffraction losses are likely to be catastrophic if the concentration of the
      excited molecules is made sufficient to ensure that the optical gain of the
      medium exceeds the losses due to the laser cavity. This imposes an extremely
      severe physical constraint on the development of a laser based on radical-ion
      annihilation.

PMID- 20134999
TI  - Tuning of a dye laser by a birefringent fabry-perot etalon.
AB  - It is shown that a birefringent Fabry-Perot etalon, which has a simple
      configuration similar to Lyot's filter except for mirror coatings on the end
      faces of birefringent crystal, is useful for tuning of dye lasers because of the
      high finesse realized by two stages of commonly used Fabry-Perot etalons.
      Experimental tuning characteristics of PbMoO(4) and LiNbO(3) birefringent Fabry
      Perot etalons in a pulsed dye laser, pumped by the second harmonic of a
      repetitively Q-switched Nd:YAG laser, are in agreement with the theory.

PMID- 20135000
TI  - Scattering in ZnO-Sapphire Optical Waveguides.
AB  - Optical waveguide loss due to scattering in epitaxial ZnO-sapphire films was
      studied by measuring the dependence of attenuation on mode number and on optical
      wavelength. Analysis of the results in terms of wave-optical scattering theory
      enabled the bulk and surface scattering contributions to be determined. The bulk
      scattering showed the lambda(-4) dependence characteristic of Rayleigh
      scattering. A white noise spectrum of surface roughness was found to be in good
      agreement with surface scattering observed in most of the waveguides studied. The
      attenuation coefficients derived from the data were related to specific aspects
      of the waveguide fabrication process and allowed rational improvements resulting
      in a decrease in loss from 20 dB/cm to 1 dB/cm.

PMID- 20135001
TI  - Quantitative Evaluation of Photoresist Patterns in the 1 - microm Range.
AB  - During exposure of photoresist layers the light distribution inside the resist is
      essentially determined by three factors: the incident light pattern generated by
      the exposure system at the resist surface; the absorption of light by the
      photoresist; and the reflected waves at the interfaces between layers. Due to
      standing wave effects, regions of different light intensity are created inside
      the resist, leading to steplike edge contours of the photoresist after
      development. The shape of photoresist patterns can be calculated.

PMID- 20135002
TI  - Mode Coupling Effects in Graded-index Optical Fibers.
AB  - Mode coupling theory is applied to the study of multimode optical fibers with
      graded-index cores. For coupling caused by random bends in the waveguide axis,
      the results predict the dependence of the induced losses on the fiber's
      characteristics. The impulse response is determined for fibers with random bends
      having several different power spectra. The results are used to predict the
      transmitted power, the delay time, and the rms pulse width in fibers with graded
      index cores.

PMID- 20135003
TI  - Two wavelength measurements of optical waveguide parameters.
AB  - Optical waveguide parameters, guide index of refraction and thickness, can be
      measured from the knowledge of mode propagation constants at two different
      wavelengths. This method is as accurate as the twomode method and can be used for
      both single-mode guides and multimode guides. The index of refraction of various
      optical components must be known at both the wavelengths; in cases where these
      indices are not directly available it is possible to interpolate this information
      from the known properties of other glasses. This paper describes the experimental
      nique. and analytical aspects of the two-wavelength measurement technique.

PMID- 20135004
TI  - Envelope gain saturation in distributed-feedback lasers.
AB  - Gain saturation is treated by formulating a model that accounts for the
      dependence of gain on irradiance level in distributed-feedback lasers. Solutions
      of the coupled-mode equations of the model are obtained numerically and are
      presented for both overcoupled and undercoupled laser structures (KL in the 10(
      13)-10 range). Parasitic losses that are distributed uniformly within the
      structure are found to influence the output power characteristics of distributed
      feedback lasers. Also the optimum coupling strength that results in the most
      efficient conversion of pump power to useful laser output is determined. The
      optimum coupling strength for any distributed-feedback laser is dependent on the
      magnitude of the parasitic losses and on the required output-power level.

PMID- 20135005
TI  - Optical thickness monitor for thin film deposition.
AB  - A monitoring technique is presented for controlling the deposition of dielectric
      films, based on periodic comparison of the reflectances of the coated and
      uncoated regions of a substrate. The device described is very simple in
      construction and operating principles; with some refinements it gives extremely
      high sensitivity for very thin (<lambda/100) films and becomes a null-detection
      monitor for lambda/4 or lambda/2 thicknesses. The monitor is suitable for
      multilayer deposition. A theoretical analysis is given, and results are presented
      to substantiate the theory for different modes of operation of the device.

PMID- 20135006
TI  - Measurement of surface strain distribution by means of color display using
      optical spatial filtering.
AB  - A method for displaying surface strain distribution in a plane plate is
      presented. The optical spatialfiltering technique is applied, where the strain
      distribution is converted to the spectrum color bands in the image plane of the
      system. The principle and experiments to show its validity are described. The
      results confirmed that the method is useful for grasping the strain state
      semiquantitatively over the whole field. With this technique a practical
      experiment for measuring strain distributions in a plane metal plate is also
      performed.

PMID- 20135007
TI  - Holographic laser beam deflector.
AB  - A mechanically rotating laser beam deflector is described that consists of
      several transmission type volume holograms recorded on a cylindrical surface. Its
      performance characteristics are compared with those of a multifacetted rotating
      mirror.

PMID- 20135008
TI  - Sandwich hologram interferometry. 2: some practical calculations.
AB  - Two hologram plates representing different object situations are bonded together
      with their emulsions separated. Fringes are formed that can be manipulated during
      reconstruction by moving the sandwich hologram in relation to the reconstruction
      beam. We have studied practical mathematical relations between sandwich motions,
      fringe changes, and object motion between the two exposures. Four dimensionless
      equations have been found that can be used for fringe evaluation by measuring
      sandwich motions. The wavelength of light is not involved in this new analogous
      compensating method. In contrast to ordinary double-exposed holograms, the
      sandwich hologram can directly reveal signs of displacements and maximal object
      strain.

PMID- 20135009
TI  - Reflective optics system for uniform spherical illumination.
AB  - A reflective optical system is described that permits nearly uniform illumination
      of a small sphere with one or two laser beams. The primary application of this
      device is to studies of laser-driven implosion of small targets. Other
      applications include the production of plasma by optical breakdown of gases for
      spectroscopic studies and for optimum light collection in intensity-limited
      plasma diagnostics. Simple calculations show that the intensity mapping
      properties of this system are not excessively sensitive to variations in the
      radial intensity distribution nor to departures from diffraction-limited
      propagation in the input beams. Optical damage and the illuminated solid angle
      required at the focus determine the size of the device.

PMID- 20135010
TI  - Aplanatic two-mirror telescopes; a systematic study. 3: the schwarzschild-couder
      configuration.
AB  - A systematic performance analysis of aplanatic Schwarzschild-Couder type
      telescopes has been carried out by means of a ray trace program. The classic
      Schwarzschild and Couder designs were studied in detail. It was found that those
      types of telescopes, in contrast to the Gregorian [Appl. Opt. 13, 2402 (1974)]
      and the Cassegrainian [Appl. Opt. 13, 2064 (1974)] configuration, suffered
      severely from higher order aberration.

PMID- 20135011
TI  - Continuum source and a focusing technique for the 80-500-a spectral range:
      improvements.
AB  - The performance of a triggered vacuum spark source, emitting continuum radiation
      in the vacuum uv down to 80 A, has been improved by adding a capillary made of
      insulating material and increasing the capacity of the condenser. A focusing
      system consisting of a toroidal mirror has been used in conjunction with the
      source and a grazing incidence spectrograph in the 500-80-A spectral range. The
      results obtained indicate considerable gains (of the order of a factor of 200)
      with respect to previously used sources, allowing photographic recording of
      spectra with only one flash while maintaining good spectral resolution.

PMID- 20135012
TI  - Automatic ellipsometer with high sensitivity and special advantages for infrared
      spectroscopy of adsorbed species.
AB  - An automated ir ellipsometer for measurements of the optical properties of thin
      adsorbed films is described. The instrument makes use of two stationary
      polarizers that bracket a rotating polarizer and the reflecting surface. This
      combination introduces modulation in the transmitted light intensity at twice and
      four times the frequency of rotation of the polarizer. The phases of these two
      frequency components are then measured in digital form relative to signals
      derived from the rotating device, the entire instrument being under automatic
      data acquisition control. A result for an ir ellipsometric study of formic acid
      chemisorbed on silver is presented.

PMID- 20135013
TI  - Chirped fourier spectroscopy. 2: theory of resolution and contrast.
AB  - When applied to a Fourier spectrometer, chirping raises questions about the
      resolution and contrast of the device. A theory is presented to show how the
      nonlinear phase affects the instrument profile and resolution; the penalty for
      chirping a high resolution interferometer is much smaller than had been believed.
      An algorithm is presented for recovering contrast; it is shown that the fast
      Fourier transform is still usable, allowing realization of full contrast. Systems
      bearing a residual nonlinear phase dispersion (accidental chirping) can take
      advantage of this theory.

PMID- 20135014
TI  - Zur rnathematischen Analyse von Oszillogrammen der kinetischen
      Absorptionsspektrophotometrie.
AB  - Measurements in kinetic absorption spectrophotometry are analyzed on the basis of
      the theory of linear systems of equations. An estimation can be made of how many
      species at least take part in the reaction. If the reactants and their absorption
      spectra are known and if the latter are linearly independent, the concentrations
      as functions of time can be calculated, too. There is no restriction to certain
      orders of reactions.

PMID- 20135015
TI  - Filter glasses for photometric application.
AB  - A program has been undertaken to investigate the preparation of new filter
      glasses for photometric use. By changing the composition of different base
      glasses containing small amounts of glass coloring metal oxides, it was possible
      to obtain new glasses with interesting transmittance properties. Gaussian-type
      spectral transmittance curves were obtained showing characteristics similar to
      some CIE standard photometric functions such as V(lambda), V'(lambda), and x
      (lambda). By slight alterations to the constituents and preparation procedure, it
      was possible to obtain shifts in the spectral transmittances enabling close
      approximation to some standard distributions. Tellurite and phosphate glasses
      with small quantities of metal oxides proved the most successful for this
      purpose.

PMID- 20135016
TI  - Controlled generation and absolute calibration of radiant incidance in low
      background test facilities for infrared space sensors.
AB  - Meaningful prelaunch calibrations of ir sensors designed to be operated from
      space platforms require lowbackground test facilities that permit both the
      controlled generation and the absolute calibration of radiant incidance over wide
      dynamic ranges. Such a test facility is presently under development. It comprises
      a source assembly, a collimator, and a spectroradiometer. The source can emit
      either broadband or monochromatic radiation. In conjunction with a reference
      blackbody, the spectroradiometer monitors both the radiant incidance and the
      spectral distribution of the flux that enters the sensor under test.

PMID- 20135017
TI  - Absolute Radiometric Calibration of Detectors Between 200-600A.
AB  - Radiometric transfer standards consisting of windowless diodes with cathodes made
      of anodized aluminum oxide on aluminum are now available from the National Bureau
      of Standards with calibrations in the 200-600-A wavelength range. This extends
      the previously existing range of calibration for these diodes (600-1200 A). For
      wavelengths shorter than 600 A, synchrotron radiation at NBS-SURF is used as the
      source of radiant energy. A noble gas double ionization chamber is used to
      calibrate a secondary standard diode that is then intercompared with the transfer
      standards. Monitors take into account variations in the intensity of synchrotron
      radiation and in beam position. Methods of accounting for the effects of second
      order radiation in the incident flux and secondary ionization in the double
      ionization chamber are discussed. Calibration uncertainties are about 10%.

PMID- 20135018
TI  - Measurement of geometrically total spectral radiant power.
AB  - In this paper, the measurement of geometrically total spectral radiant power,
      i.e., the spectral radiant power emanating in all directions from a light source,
      is discussed. A gonioradiometer employing a silicon photodiode and a set of
      narrow band interference filters was used for these measurements. The experiment
      is described, some exploratory measurements are presented, and the uncertainties
      which this method introduces are estimated.

PMID- 20135019
TI  - Prucalopride for chronic constipation.
AB  - Chronic constipation is a frequently reported medical disorder that reduces
      patients' quality of life and imposes a significant economic burden on the health
      care system. Symptoms of constipation are diverse and include infrequent bowel
      movements, hard stool, straining at stool, sensations of anorectal obstruction
      and feelings of incomplete evacuation. Patients with chronic constipation can be
      categorized into one of three main groups based on their underlying
      pathophysiology: normal transit constipation; colonic inertia; and pelvic floor
      dyssynergia. Specialized tests (i.e., anorectal manometry, radio-opaque marker
      study) may be required in some patients to help distinguish the different
      subtypes of constipation and to guide appropriate therapy. Although the
      underlying mechanism of constipation differs among patients, serotonin (5
      hydroxytryptamine (5-HT)) appears to have an important role in colonic motility
      in some patients. Previous research has demonstrated that stimulation of 5-HT4
      receptors improves symptoms of chronic constipation in some patients.
      Prucalopride, a selective 5-HT4 agonist, relieved symptoms of constipation in
      phase II and phase III clinical trials. In this monograph, we review the
      pharmacology, mechanism of action, efficacy and safety of the selective 5-HT4
      agonist prucalopride in patients with chronic constipation.

PMID- 20135020
TI  - Icatibant for hereditary angioedema.
AB  - Hereditary angioedema (HAE) is an autosomal dominant, potentially life
      threatening disease, characterized by recurrent self-limiting bouts of edema
      mainly involving the extremities, genitalia, face, intestines and airways. The
      prevalence of HAE in the general population has been estimated to be in the range
      of 1:10,000 to 1:150,000. Currently, acute attacks of HAE are treated mainly
      symptomatically, with poor outcomes. Recently, it has been demonstrated that
      bradykinin (BK) is responsible for most of the symptoms of HAE. Icatibant
      (Firazyr, HOE 140, JE049) is a potent, specific and selective B2 BK receptor
      antagonist that has recently been approved by the EMEA for the treatment of HAE.
      In phase III clinical trials, 30 mg of subcutaneous icatibant demonstrated rapid
      and stable relief from symptoms in cutaneous, abdominal or laryngeal HAE attacks.
      Local site reactions after subcutaneous injection of icatibant were observed,
      however, these reactions were mild to moderate in severity and resolved
      spontaneously and quickly. Icatibant is a new, safe and effective treatment for
      acute attacks of HAE.

PMID- 20135021
TI  - Asenapine maleate: a new drug for the treatment of schizophrenia and bipolar
      mania.
AB  - Schizophrenia and bipolar disorder are serious neuropsychiatric disorders with
      substantial health risks for patients that result in major socioeconomic burdens
      on society. Current therapeutic agents fail to adequately address patient needs
      in terms of efficacy, tolerability and treatment-related adverse events.
      Consequently there is an urgent need to develop more effective and better
      tolerated pharmacotherapies for improved treatment of these illnesses. Asenapine
      maleate is a novel drug recently approved by the Food and Drug Administration for
      treatment of acute schizophrenia and for manic or mixed episodes of bipolar I
      disorder with or without psychotic features in adults. It has a unique
      pharmacologic profile as it targets multiple dopamine, serotonin and adrenergic
      receptor subtypes with variable affinities. Such drug/receptor interactions
      contribute to the antipsychotic and antimanic efficacy of asenapine. Asenapine
      was effective in animal models predictive of antipsychotic activity and clinical
      trials indicate that it improves the symptoms of acute schizophrenia and bipolar
      mania, is well tolerated and has a favorable safety profile. This monograph
      provides an up to date review of the preclinical and clinical profiles of
      asenapine, including new clinical data in patients with schizophrenia and bipolar
      mania.

PMID- 20135022
TI  - Association of phosphatidylcholine and NSAIDs as a novel strategy to reduce
      gastrointestinal toxicity.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective drugs that
      inhibit pain and inflammation, and perhaps due to the role of inflammation in the
      underlying etiology, NSAIDs have also demonstrated efficacy in reducing a
      patient's risk of developing a number of cancers and neurological diseases (e.g.
      Alzheimer's disease). The utility of these powerful drugs is limited due to their
      gastrointestinal (GI) side-effects, notably peptic ulceration and GI bleeding
      which is briefly reviewed here. We also describe the barrier property of the GI
      mucosa and how it is affected by NSAIDs, as it is our position that disruption of
      the surface barrier is an important component in the drugs' pathogenesis, in
      addition to selective inhibition of COX-2, which has proven to be problematic. We
      also discuss current alternative approaches being taken to mitigate the GI side
      effects of NSAIDs, including developing combination drugs where NSAIDs are
      packaged with inhibitors of HCl secretion such as proton pump inhibitors or H2
      receptor antagonists. We then present the rationale for the development of the PC
      associated NSAID technology which came out of our observation that the mammalian
      gastric mucosa has hydrophobic, nonwettable properties that provides a barrier to
      luminal acid, and the role of phospholipids and specifically phosphatidylcholine
      (PC) in this barrier property. In the last section we review the development of
      our current lipid-based PC-NSAID formulations and our encouraging preclinical and
      clinical observations validating their GI safety and therapeutic efficacy.

PMID- 20135026
TI  - Getting a chemical handle on protein post-translational modification.
AB  - This article highlights the emerging field of chemical proteomics, a powerful
      technology for the study of post- and co-translational modification of proteins.
      Genome mapping and the study of protein post-translational modifications have
      revealed the astounding chemical complexity present in the proteome of even the
      simplest organisms. The identification and characterisation of the modifications
      present on specific proteins in such complex mixtures has become a central
      challenge for post-genomic functional studies in cell and systems biology. In the
      chemical proteomic approach to this problem, protein-modifying enzymes and
      bioorthogonal chemoselective elaboration are exploited to deliver chemical tags
      to specific modified residues, enabling new advances in our understanding of
      protein modification.

PMID- 20135027
TI  - Steroid hormones controlling the life cycle of the nematode Caenorhabditis
      elegans: stereoselective synthesis and biology.
AB  - Cholesterol-derived hormones, the dafachronic acids, play a major role in
      controlling the life cycle and initiating dauer larva formation of the nematode
      Caenorhabditis elegans. This Perspective describes recent progress in the
      synthesis of these steroid hormones and their biological function.

PMID- 20135028
TI  - Chemoenzymatic and enantiodivergent routes to 1,2-ring-fused bicyclo[2.2.2]octane
      and related tricyclic frameworks.
AB  - New and simple protocols are described for the conversion of the enzymatically
      derived and enantiomerically pure cis-1,2-dihydrocatechol (X = I) and its 6
      methylated derivative into either antipodal form of compounds embodying the
      tricyclic frameworks of terpenoids . Key steps include intramolecular Diels-Alder
      (IMDA) and (in some cases) singlet or triplet-based photochemical processes.

PMID- 20135029
TI  - Enantioselective construction of lactone[2,3-b]piperidine skeletons via
      organocatalytic tandem reactions.
AB  - A highly enantioselective construction of delta- and gamma-lactone[2,3
      b]piperidine skeletons was accomplished by tandem aza-Diels-Alder reaction
      hemiacetal formation-oxidation from N-Tos-1-aza-1,3-butadienes and aliphatic
      dialdehydes.

PMID- 20135030
TI  - Enantioselective desymmetrizing palladium catalyzed carbonylation reactions: the
      catalytic asymmetric synthesis of quaternary carbon center containing 1,3-dienes.
AB  - A desymmetrization protocol has been used to develop a palladium catalyzed
      enantioselective carbonylation process. Achiral cyclic bis-alkenyltriflates are
      converted to their corresponding monoester derivatives with selectivities of up
      to 96% ee.

PMID- 20135031
TI  - A novel pseudo four component reaction involving homoenolate for the synthesis of
      gamma-aminobutyric acid (GABA) derivatives.
AB  - Homoenolate generated from alpha,beta-unsaturated aldehydes by NHC catalysis
      underwent facile addition to conjugated sulfonimines, generated in situ, and
      subsequent methanolysis to afford protected GABA derivatives stereoselectively
      and in high yields, thus constituting a novel pseudo four component reaction.

PMID- 20135032
TI  - Solid state stabilisation of the orally delivered drugs atenolol, glibenclamide,
      memantine and paracetamol through their complexation with cucurbit[7]uril.
AB  - The inclusion of the cardiovascular beta-blocker drug atenolol, the antidiabetic
      drug glibenclamide, the Alzheimer's NMDA glutamate receptor drug memantine and
      the analgesic/antipyretic drug paracetamol by cucurbit[7]uril (CB[7]) has been
      studied by (1)H nuclear magnetic resonance spectroscopy, electrospray ionisation
      mass spectrometry, molecular modelling, fluorescence displacement assays and
      differential scanning calorimetry. All four drugs form 1 : 1 host-guest complexes
      with CB[7], but the exchange kinetics and location of the binding is different
      for each drug. Atenolol is bound over the central phenyl ring with a binding
      constant of 4.2 x 10(4) M(-1), whereas glibenclamide is bound over the terminal
      cyclohexyl group with a binding constant of 1.7 x 10(5) M(-1), and memantine is
      totally bound within the CB[7] cavity. Paracetamol is bound in two locations,
      over the central phenyl ring and over the methyl group, with the CB[7] molecule
      shuttling quickly between the two sites. Inclusion by CB[7] was shown by
      differential scanning calorimetry to physically stabilise all four drugs, which
      has applications preventing drug degradation and improving drug processing and
      formulation.

PMID- 20135033
TI  - Solvent-induced switching between two supramolecular assemblies of a guanosine
      terthiophene conjugate.
AB  - We report here our findings on a lipophilic guanosine derivative armed with a
      terthiophene unit that undergoes a pronounced variation of its supramolecular
      organisation by changing the polarity of the solvent. In chloroform the guanosine
      derivative, templated by alkali metal ions, assembles via H-bonding in G-quartet
      based D(4)-symmetric octamers; the polar guanine bases are located into the inner
      part of the assembly and act as a scaffold for the terthienyl pendants. On the
      other hand, in the more polar (and H-bond competing) acetonitrile, different
      aggregates are observed in which the terthiophene chains are pi-pi stacked in a
      helicoidal (left-handed) arrangement in the central core, and the guanine bases
      (free from hydrogen bonding) are located at the periphery and exposed to the
      solvent. The system can be switched back and forth by subsequent addition of
      chloroform and acetonitrile. The solvent-induced switching can be easily followed
      by circular dichroism spectroscopy: the CD exciton-couplet in the guanine
      chromophore absorption region observed in chloroform disappears after addition of
      acetonitrile, indicating the disassembly of the G-quartet based octameric
      structure, while an intense quasi-conservative exciton splitting in the 300-450
      nm spectral region becomes predominant in the CD spectrum. This latter strong
      bisignate optical activity can be ascribed to the helical packing of conjugated
      terthiophene moieties stabilised by pi-pi interactions. NMR spectra and
      photophysical investigations confirm the structures of the guanine-directed and
      thiophene-directed assemblies in chloroform and acetonitrile, respectively.

PMID- 20135034
TI  - Site-selective immobilisation of functional enzymes on to polystyrene
      nanoparticles.
AB  - The immobilisation of proteins on to nanoparticles has a number of applications
      ranging from biocatalysis through to cellular delivery of biopharmaceuticals.
      Here we describe a phosphopantetheinyl transferase (Sfp)-catalysed method for
      immobilising proteins bearing a small 12-mer "ybbR" tag on to nanoparticles
      functionalised with coenzyme A. The Sfp-catalysed immobilisation of proteins on
      to nanoparticles is a highly efficient, single step reaction that proceeds under
      mild conditions and results in a homogeneous population of proteins that are
      covalently and site-specifically attached to the surface of the nanoparticles.
      Several enzymes of interest for biocatalysis, including an arylmalonate
      decarboxylase (AMDase) and a glutamate racemase (GluR), were immobilised on to
      nanoparticles using this approach. These enzymes retained their activity and
      showed high operational stability upon immobilisation.

PMID- 20135035
TI  - Helix propensities of conformationally restricted amino acids. Non-natural
      substitutes for helix breaking proline and helix forming alanine.
AB  - Alpha helices are useful scaffolds to build biologically active peptides. The
      intrinsic stability of an alpha-helix is a key feature that can be successfully
      designed, and it is governed by the constituting amino acid residues. Their
      individual contributions to helix stability are given, according to Lifson-Roig
      theory, by their w parameters, which are known for all proteinogenic amino acids,
      but not for non-natural ones. On the other hand, non-natural, conformationally
      restricted amino acids can be used to impart biochemical stability to peptides
      intended for in vivo administration. Efficient design of peptides based on these
      amino acids requires the previous determination of their w parameters. We begin
      here this task by determining the w parameters of two restricted analogs of
      alanine: (alpha-methyl)alanine and 1-aminocyclopropanecarboxylic acid. According
      to their w values (alpha-methyl)alanine is almost as good a helix forming residue
      as alanine, while 1-aminocyclopropanecarboxylic acid is, similarly to proline, a
      helix breaker.

PMID- 20135036
TI  - Improved enzymatic syntheses of valuable beta-arylalkyl-beta-amino acid
      enantiomers.
AB  - The enantioselective (E approximately 200) Burkholderia cepacia-catalysed
      hydrolyses of beta-amino esters with H(2)O (0.5 equiv.) in t-BuOMe or in i-Pr(2)O
      at 45 degrees C are described. The enantiomers of biologically relevant beta
      arylalkyl-substituted beta-amino acids, and especially (R)-3-amino-3-(2,4,5
      trifluorophenyl)butanoic acid, the intermediate of the new antidiabetic drug
      sitagliptine, were prepared with high enantiomeric excesses (ee>or=96%) and in
      good yields (>or=42%).

PMID- 20135037
TI  - Photochemistry of dihydrobiopterin in aqueous solution.
AB  - Dihydrobiopterin (H(2)Bip) and its oxidized analogue, biopterin (Bip), accumulate
      in the skin of patients suffering from vitiligo, a chronic depigmentation
      disorder in which the protection against UV radiation fails. The photochemistry
      of H(2)Bip was studied in neutral aqueous solutions upon UV-A irradiation (320
      400 nm) at room temperature. The photochemical reactions were followed by UV/vis
      spectrophotometry, HPLC and enzymatic methods for hydrogen peroxide (H(2)O(2))
      determination. Photoproducts were analyzed by means of electrospray ionization
      mass spectrometry. Under anaerobic conditions, excitation of H(2)Bip leads to the
      formation of at least two isomeric dimers with molecular masses equal to exactly
      twice the molecular mass of the reactant. This reaction takes place from the
      singlet excited state of the reactant. To the best of our knowledge, this is the
      first time that the photodimerization of a dihydropterin is reported. In the
      presence of air, the dimers are again the main photoproducts at the beginning of
      the reaction, but a small proportion of the reactant is converted into Bip. As
      the reaction proceeds and enough Bip accumulates in the solution, a
      photosensitized process starts, where Bip photoinduces the oxidation of H(2)Bip
      to Bip, and H(2)O(2) is formed. As a consequence, the rates of H(2)Bip
      consumption and Bip formation increase as a function of irradiation time,
      resulting in an autocatalytic photochemical process. In this process, Bip in its
      triplet excited state reacts with the ground state of H(2)Bip. The mechanisms
      involved are analyzed and the biological implications of the results are
      discussed.

PMID- 20135038
TI  - The enantioselective total synthesis of nemotin.
AB  - The allene-diyne natural product nemotin was synthesized for the first time
      through an enantioselective route with the stereogenic center at the lactone
      moiety derived from l-glutamic acid and the allene axis constructed from the
      corresponding propargylic tosylate, and the absolute configuration was thus
      established as (4S,5aS).

PMID- 20135039
TI  - On the question of stepwise vs. concerted cleavage of RNA models promoted by a
      synthetic dinuclear Zn(II) complex in methanol: implementation of a noncleavable
      phosphonate probe.
AB  - To address the question of concerted versus a stepwise reaction mechanisms for
      the cyclization of the 2-hydroxypropyl aryl and alkyl RNA models (1a-k) promoted
      by dinuclear Zn(II) complex (4) at (s)spH 9.8 and 25 degrees C, the non-cleavable
      O-hydroxypropyl phenylphosphonate analogues 6a and 6b were subjected to the
      catalytic reaction in methanol. These phosphonates did not undergo isomerization
      in the study, the only observable methanolysis reaction being release of 1,2
      propanediol and the formation of O-methyl phenylphosphonate. The observed first
      order rate constants for methanolysis promoted by 4 are k(obs)(6a) = (1.47 +/-
      0.09) x 10(-4) s(-1) and k(obs)(6b) = (2.08 +/- 0.09) x 10(-6) s(-1),
      respectively. The rates of methanolysis of a series of O-aryl phenylphosphonates
      (8a-f) in the presence of increasing [4] were analyzed to provide binding
      constants, Kb, and the catalytic rate constant, kcat(max), for the unimolecular
      decomposition of the 8:4 Michaelis complex. A Bronsted plot of the log
      (k(cat)(max)) vs. sspKa(phenol) (acidity constant of the conjugate acid of the
      leaving group in methanol) was fitted to a linear regression of log kcat(max) = (
      0.80 +/- 0.07)(s)spKa + (10.2 +/- 1.0) which includes the datum for 6a. The datum
      for 6b, which reacts approximately 70-fold slower, falls significantly below the
      linear correlation. The data provide additional evidence consistent with a
      concerted cyclization of RNA models 1a-k promoted by 4.

PMID- 20135040
TI  - 5-Selenization of salicylic acid derivatives yielded isoform-specific 5
      lipoxygenase inhibitors.
AB  - Low molecular weight seleno-organic compounds exhibit glutathione peroxidase
      (GPx)-like activity; the well-known compound ebselen is being used in clinical
      trials as a stroke medication. Here, we describe the facile one-step synthesis of
      novel 5-selenized salicylic acid derivatives using selenium tetrachloride. The
      products were analyzed by spectroscopic studies including (77)Se-NMR and some
      were subjected to X-ray structure determination. Several products were identified
      as selective inhibitors of the pro-inflammatory 5-lipoxygenase (LOX) but had
      little effect on the catalytic activity of 12/15-LOX, which has been implicated
      in the synthesis of anti-inflammatory mediators. Such isoform-specificity
      (specificity coefficient >120) has not been reported before for any seleno
      organic compound. In addition, synthesis products exhibited GPx-like activity,
      which was higher than that of ebselen for some derivatives.

PMID- 20135041
TI  - New and simple synthesis of acid azides, ureas and carbamates from carboxylic
      acids: application of peptide coupling agents EDC and HBTU.
AB  - Conversion of carboxylic acids into acid azides using peptide coupling agents,
      EDC and HBTU is described. The procedure is efficient, practical and applicable
      to a diverse range of carboxylic acids including N-protected amino acids. Using
      the same reagents, one-pot synthesis of ureas, dipeptidyl urea esters and
      carbamates from acids has also been achieved.

PMID- 20135042
TI  - Ligand-free copper(I)-catalysed intramolecular direct C-H functionalization of
      azoles.
AB  - The first examples of copper-catalysed intramolecular direct C-arylation of
      azaheterocycles for the synthesis of complex heterofused compounds is presented,
      featuring an unprecedented arylation via C-H activation of 9H-purine and 4
      azabenzimidazole.

PMID- 20135043
TI  - Insight into the mechanism of action of plakortins, simple 1,2-dioxane
      antimalarials.
AB  - A multidisciplinary approach, based on molecular dynamics/mechanics, ab initio
      calculations, dynamic docking studies, and chemical reactions, has been employed
      to gain insight into the mechanism of the antimalarial action of plakortin and
      dihydroplakortin, simple 1,2-dioxanes isolated from the sponge Plakortis simplex.
      Our results show that these molecules, after interaction of the endoperoxide bond
      with Fe(ii), likely coming from the heme molecule, give rise to the formation of
      an oxygen radical, followed by rearrangement to give a carbon radical centered on
      the "western" alkyl side-chain. The carbon radicals generated on the side-chain,
      amenable for intermolecular reactions, should represent the toxic intermediates
      responsible for subsequent reactions leading to plasmodium death. The minimal
      structural requirements necessary for the activity of this class of antimalarial
      agents have been identified and discussed throughout the paper.

PMID- 20135044
TI  - A new model for mapping the peptide backbone: predicting proton chemical shifts
      in proteins.
AB  - This paper describes a methodology that correlates experimental chemical shifts
      (at the alpha proton) of proteins with their geometrical data (both dihedral
      angles and distances) obtained from 13 representative proteins, which are taken
      from the Protein Data Bank (PDB) and the BioMagRes Data Bank (BMRB). To this end,
      the experimentally measured proton chemical shifts of simple amides have been
      correlated with DFT-based calculated structures, at the B3PW91/6-31G* level. This
      results in a series of mathematical relationships, which are extrapolated to the
      above-mentioned proteins giving rise to a modified equation for such skeleta. It
      is relevant to note that the equation is also supported by a clear comparison
      with NMR data of a protein beyond the chosen set, such as insulin, even with
      lower errors. The model also relates the dependence of chemical shifts on
      hydrophobic and anisotropic effects at the amino acid residues.

PMID- 20135045
TI  - MiPNO, a new chiral cyclic nitrone for enantioselective amino acid synthesis: the
      cycloaddition approach.
AB  - The resolution of chiral nitrones via derivatization of hydroxylamines was
      applied to MiPNO, a new, stable, easily prepared chiral cyclic nitrone. The
      application of MiPNO in totally regio- and diastereo-selective 1,3-dipolar
      cycloaddition reactions provides an expeditious enantioselective access to
      unusual gamma-hydroxy alpha-amino acids.

PMID- 20135046
TI  - Mechanism of general acid-base catalysis in transesterification of an RNA model
      phosphodiester studied with strongly basic catalysts.
AB  - Using 80% vol aqueous DMSO as the reaction medium for transesterification of an
      RNA model substrate 2-hydroxypropyl 4-nitrophenyl phosphate allows one to observe
      catalysis in buffer mixtures composed of highly basic components such as
      guanidines, amidines or alkylamines, which provide up to 10(3)-fold accelerations
      over the background reaction in the 0.01-0.1 M concentration range. The rate law
      k(obs) = k(1)[B] + k(2)[B][BH(+)] was established indicating contributions from
      both simple general base catalysis and the reaction involving concerted action of
      neutral (B) and protonated (BH(+)) forms of the buffer. The catalytic efficiency
      of guanidinium and amidinium cations is 10 times larger than that of more acidic
      ammonium cations. Rate constants k(1) and k(2) obey the Bronsted equations with
      the slopes 0.77 and 0.69 respectively. Proton inventory for k(2) (B = guanidine)
      in D(2)O/H(2)O mixtures gives two fractionation factors phi(1) = 0.48 and phi(2)
      = 1.26 for normal and inverse isotope effects respectively. The former results
      from the proton transfer to B and the latter from the binding of guanidinium
      cation to the phosphate group as follows from observation of an inverse solvent
      isotope effect for the binding of guanidinium and amidinium cations to a
      phosphodiester anion. The results of kinetic studies together with analysis of
      transition state stabilization free energies for guanidinium and amidinium
      cations show that the protonated buffer component acts via electrostatic
      transition state stabilization rather than proton transfer, which may be possible
      for a guanidinium assisted hydroxide catalyzed reaction.

PMID- 20135047
TI  - Synthesis of 3-hydroxy-5-alkoxyhomophthalates by domino '2 : 1
      coupling/intramolecular aldol condensation' reactions of 1,3
      bis(trimethylsilyloxy)-1,3-butadienes with tetraalkoxymethanes.
AB  - The first domino '2 : 1 condensation/intramolecular aldol' reactions of 1,3
      bis(trimethylsilyloxy)-1,3-butadiene with tetraalkoxymethanes provide a
      convenient approach to 3-hydroxy-5-alkoxyhomophthalates. These products, which
      contain one free and one protected hydroxyl group, can be functionalized by
      palladium(0)-catalyzed cross-coupling reactions.

PMID- 20135048
TI  - Formation and hydrolysis of amide bonds by lipase A from Candida antarctica;
      exceptional features.
AB  - Various commercial lyophilized and immobilized preparations of lipase A from
      Candida antarctica (CAL-A) were studied for their ability to catalyze the
      hydrolysis of amide bonds in N-acylated alpha-amino acids, 3-butanamidobutanoic
      acid (beta-amino acid) and its ethyl ester. The activity toward amide bonds is
      highly untypical of lipases, despite the close mechanistic analogy to amidases
      which normally catalyze the corresponding reactions. Most CAL-A preparations
      cleaved amide bonds of various substrates with high enantioselectivity, although
      high variations in substrate selectivity and catalytic rates were detected. The
      possible role of contaminant protein species on the hydrolytic activity toward
      these bonds was studied by fractionation and analysis of the commercial
      lyophilized preparation of CAL-A (Cat#ICR-112, Codexis). In addition to minor
      impurities, two equally abundant proteins were detected, migrating on SDS-PAGE a
      few kDa apart around the calculated size of CAL-A. Based on peptide fragment
      analysis and sequence comparison both bands shared substantial sequence coverage
      with CAL-A. However, peptides at the C-terminal end constituting a motile domain
      described as an active-site flap were not identified in the smaller fragment.
      Separated gel filtration fractions of the two forms of CAL-A both catalyzed the
      amide bond hydrolysis of ethyl 3-butanamidobutanoate as well as the N-acylation
      of methyl pipecolinate. Hydrolytic activity towards N-acetylmethionine was,
      however, solely confined to the fractions containing the truncated form of CAL-A.
      These fractions were also found to contain a trace enzyme impurity identified in
      sequence analysis as a serine carboxypeptidase. The possible role of catalytic
      impurities versus the function of CAL-A in amide bond hydrolysis is further
      discussed in the paper.

PMID- 20135049
TI  - Cross-coupling reaction of alcohols for carbon-carbon bond formation using pincer
      type NHC/palladium catalysts.
AB  - A cross-coupling reaction of different alcohols was achieved using a pincer-type
      NHC/PdBr complex as the catalyst precursor, and the reaction, under either Ar or
      H(2) gas, displayed a broad substrate scope with respect to both primary and
      secondary alcohol components, with high alcohol product selectivity.

PMID- 20135050
TI  - Nucleophilic heterocyclic carbene as a novel catalyst for cyclopropanation of
      cyano acrylates.
AB  - Nucleophilic heterocyclic carbenes (NHCs) have been used for the first time as
      catalysts in the cyclopropanation of ethyl cyanocinnamates with phenacyl bromide
      by Michael-initiated ring-closure (MIRC).

PMID- 20135051
TI  - Glucosylthioureidocalix[4]arenes: Synthesis, conformations and gas phase
      recognition of amino acids.
AB  - The gas-phase recognition of native amino acids and the conformational properties
      of three glucosylthioureidocalix[4]arenes () were studied theoretically and
      experimentally using ab initio calculations, ESI-FTICR,(1)H and (13)C NMR MS. The
      conformational and complexation properties of the glucocalixarenes were dependent
      on the number of glucose units at the upper rim and the length of the alkyl
      chains at the lower rim of the calixarene skeleton. ESI-MS experiments showed the
      compounds to form 1 : 1 complexes with the amino acids, with a marked preference
      for amino acids containing an aromatic nucleus and an additional H-bonding group
      in their side chain (Trp, Tyr, Phe >> Ser, Leu and Asp). The experimental data
      were rationalized by the results of ab initio calculations. ESI-MS competitions
      carried out with enantiomeric-labelled (EL) amino acids showed enantiomeric
      selectivities ranging from 0.61 (Phe(D)/Phe(L) with ligand ) to 2.58
      (Tyr(D)/Tyr(L) with ligand ). In gas-phase hydrogen-deuterium (H/D) exchange
      reactions, diglucosylcalix[4]arene exhibited extremely slow exchange rates, which
      were attributed to the close proximity and strong hydrogen bonding between the
      facing glucosylthioureido groups. H/D exchange rates were much higher for the
      tetraglucosylcalix[4]arenes and and their amino acid complexes, and the more
      rigid tetrapropoxy derivative showed more selective H/D exchange reactions than
      the calixarene . Bi- or trimodal H/D exchange distribution was observed for the
      tetraglucosyl derivatives indicating that these ligands exist in multiple
      isomeric forms in gas phase.

PMID- 20135052
TI  - Evaluation of stereochemically dense morpholine-based scaffolds as proline
      surrogates in beta-turn peptides.
AB  - Four peptides differing for the structure of the new morpholine-based
      heterocyclic compound acting as a turn inducer were synthesized in solution
      phase, and the conformational preferences were assessed by means of NMR analysis.
      All spectroscopic data revealed an adaptive behaviour of the turn peptides in
      generating turn conformations stabilized by intramolecular hydrogen-bonds,
      despite the conformational changes of the turn inducer. Thus, this study suggests
      the possibility of functionalizing morpholine-containing beta-turn peptides with
      no significant loss of the secondary framework. The 3,4-dihydro-2H-[1,4]oxazine
      containing peptide showed a more compact structure stabilized by an additional
      gamma-turn-forming hydrogen-bond experienced by the Gly amide proton.

PMID- 20135055
TI  - Understanding the complexity of abciximab-related thrombocytopenia.

PMID- 20135056
TI  - Anticoagulation therapy and the risk of stroke in patients with atrial
      fibrillation at 'moderate risk' [CHADS2 score=1]: simplifying stroke risk
      assessment and thromboprophylaxis in real-life clinical practice.

PMID- 20135057
TI  - Changing the scope of preventative and therapeutic approaches in
      atherothrombosis.

PMID- 20135058
TI  - Low-molecular-weight heparin from Cu2+ and Fe2+ Fenton type depolymerisation
      processes.
AB  - Hydrogen peroxide (H2O2) and Cu(OAc)2 or FeSO4 (Fenton type reagents) perform
      heparin (Hep) depolymerisation to low-molecular-weight heparin (LMWH) following a
      radical chain mechanism. Hydroxyl (OH) radicals which are initially generated
      from H2O2 reduction by transition metal ions abstract hydrogen atoms on the
      heparin chain providing carbon centred radicals whose decay leads to the
      depolymerisation process. The main depolymerisation mechanism involves Hep
      radical intermediates that cleave the glycosidic linkage at unsulphated uronic
      acids followed by a 6-O-nonsulphated glucosamine, thus largely preserving the
      pentasaccharide sequence responsible for the binding to antithrombin III (AT).
      Both the transition metal ions influence the overall efficiency of the radical
      chain processes: Fe2+ acting as a catalyst, while Cu2+ acts as a reagent. LMWHs,
      especially those afforded by Cu2+, are somewhat unstable to the usual basic
      workup. However, this lack of stability can be eliminated by a previous NaBH4
      reduction. Furthermore, with Cu2+, the process is much more reproducible than
      with Fe2+. Therefore, for the process of Fenton type depolymerisation of heparin,
      the use of Cu(OAc)2 is clearly preferable to the more "classical" FeSO4. The
      resulting activities and characteristics of these LMWHs are peculiar to these
      oxidative radical processes. In addition, LMWH provided by H2O2/Cu(OAc)2 in
      optimised conditions was found to posses anti-Xa and anti-IIa activities
      comparable to those of LMWHs currently in clinical use.

PMID- 20135059
TI  - Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa
      inhibitor.
AB  - Although there is no need for routine coagulation monitoring with rivaroxaban--an
      oral, direct factor Xa inhibitor--a haemostasis assay might be valuable to
      measure its pharmacodynamic effects. This study aimed to find assays, among those
      commercially available, to measure rivaroxaban pharmacodynamics. Several global
      conventional clotting tests, as well as clotting or chromogenic assays to measure
      anti-factor Xa activity, were studied. A thrombin generation test using
      calibrated automated thrombogram was also done. Tests were performed with the
      indirect factor Xa inhibitor fondaparinux for comparison. A concentration
      dependent prolongation of prothrombin time (PT), dilute PT, and activated partial
      thromboplastin time was observed with rivaroxaban. The results varied depending
      on the reagents. This variability cannot be standardised with the international
      normalised ratio system commonly used for vitamin K antagonists. Using a standard
      calibration curve, PT test results can be expressed in plasma concentrations of
      rivaroxaban rather than PT seconds or ratio. Standard methods for HepTest and two
      step prothrombinase-induced clotting time (PiCT) resulted in a paradoxical
      response, with low concentrations of rivaroxaban reducing clotting times. This
      was not observed with shorter incubation times, or when antithrombin-deficient
      (immunodepleted) plasma was used. The chromogenic tests found a dose-dependent
      relationship between anti-factor Xa activity and rivaroxaban concentration.
      Modified specific factor Xa chromogenic assays are being further investigated.
      One-step PiCT and HepTest with shortened incubation times, as well as the widely
      available PT assay (using a rivaroxaban calibrator) could be useful to monitor
      the pharmacodynamic effects of rivaroxaban accurately. Finally, all clotting and
      chromogenic assays showed a concentration-dependent effect induced by
      rivaroxaban.

PMID- 20135060
TI  - 8-pCPT-conjugated cyclic AMP analogs exert thromboxane receptor antagonistic
      properties.
AB  - Membrane-permeable 8-(4-chlorophenylthio)-2'-O-methyl cyclic AMP (8-pCPT-2'-O-Me
      cAMP) has been shown to specifically activate cAMP-regulated Epac proteins,
      without direct effects on protein kinase A and protein kinase G. During isometric
      tension measurements in thoracic aortic rings from Wistar rats, we observed that
      8-pCPT-2'-O-Me-cAMP selectively induced a rightward shift of the concentration
      response curve for the thromboxane mimetic U46619, without altering the
      contractile response to noradrenaline. We hypothesised that 8-pCPT-2'-O-Me-cAMP
      and similar compounds may function as direct thromboxane receptor antagonists.
      Indeed, in addition to 8-pCPT-2'-O- Me-cAMP, also 8-pCPT-cAMP, 8-(4
      chlorophenylthio)-adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8
      CPT-cAMPS) and 8-CPT-adenosine, but not 8-Bromo-2'-O-Me-cAMP, induced rightward
      shifts of the contractile response to U46619. Likewise, 8-pCPT-2'-O- Me-cAMP and
      Rp-8-CPT-cAMPS, but not 8-Bromo-2'-O-Me-cAMP, specifically reduced U46619-induced
      aggregation of human platelets. In addition, 8-pCPT-2'-O-Me-cAMP and Rp-8-CPT
      cAMPS completely reversed U46619-induced reduction of intercellular adhesion
      molecule-1 expression and migration of human coronary artery endothelial cells.
      Most important, the cAMP analogs that reduced the contractile response to U46619
      also concentration-dependently inhibited binding of the thromboxane receptor
      radioligand [5,6-3H]SQ29548 to human platelets. We conclude that 8-pCPT
      conjugated cAMP analogs exert competitive thromboxane receptor antagonistic
      properties.

PMID- 20135061
TI  - Adrenergic receptor polymorphisms and platelet reactivity after treatment with
      dual antiplatelet therapy with aspirin and clopidogrel in acute coronary
      syndrome.
AB  - Platelet response to clopidogrel shows inter-individual variability that is
      partially explained by genetic polymorphisms. This variability affects clinical
      outcome when clopidogrel is administered in patients with acute coronary syndrome
      (ACS). Catecholamines, released during ACS, contribute to platelet aggregation
      through platelet alpha2A-(alpha2A-AR) and beta2-adrenergic receptor (beta2-AR)
      stimulation. It was the objective of this study to assess the potential influence
      of alpha2A-AR and beta2-AR gene polymorphisms on platelet reactivity after dual
      antiplatelet therapy with aspirin and clopidogrel in ACS. We screened 641 ACS
      patients for 6.3/6.7 kb alpha2A-AR polymorphism, and for Arg16Gly and Gln27Glu
      beta2-AR polymorphism. After 600 mg clopidogrel, we assessed ADP 10 micromol
      induced platelet aggregation (ADP-Ag) and vasoactive stimulated phosphoprotein
      (VASP). All single nucleotide polymorphisms were in Hardy-Weinberg equilibrium. A
      slight though negligible association was found between 6.3 kb allele of alpha2A
      AR with platelet reactivity ADP-Ag induced (beta: -2.91 [-5.68;-0.14], p=0.04). A
      borderline not significant reduction in PRI VASP was observed in 6.3 kb alpha2A
      AR carriers (beta: -3.81 [-0.09;7.72], p=0.06). No significant effect on platelet
      parameters was observed for the other tested polymorphisms. Common alpha2A- and
      beta2-adrenergic receptor polymorphisms do not show any major impact on residual
      platelet reactivity in non-ST-elevation ACS when a dual antiplatelet therapy with
      250 mg aspirin and 600 mg clopidogrel is administered.

PMID- 20135062
TI  - Characterisation of a novel nonsense mutation in FGG (Fibrinogen Poznan) causing
      hypofibrinogenaemia with a mild bleeding tendency.

PMID- 20135063
TI  - Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated
      meta-analysis.
AB  - We performed this meta-analysis to update the clinical evidences on the relation
      between clopidogrel non-responsiveness and clinical outcomes in patients with
      coronary artery disease (CAD) who underwent percutaneous coronary intervention.
      An electronic literature search through MEDLINE, EMBASE, Web of Science, and the
      Cochrane Library and bibliographies of retrieved articles up to January, 2009 was
      conducted. Studies were included if they had a cohort prospective design, if they
      analysed clopidogrel responsiveness in CAD patients in relation to death and/or
      occurrence of adverse coronary events during follow-up, and if they reported an
      adequate statistical analysis. Fourteen studies, totalling 4,564 CAD patients
      followed for a time ranging from 14 days to one year, were included. The
      cumulative analysis reported that residual platelet reactivity despite
      clopidogrel treatment was significantly associated with an increased risk of
      death and/or thrombotic recurrences (odds ratio [OR] 5.67, 95% confidence
      interval [CI] 2.97 to 10.84; p<0.00001). However, four studies contributed to a
      consistent heterogeneity of the model and evidenced a significant risk of
      publication bias, so were excluded from the analysis. This exclusion, however,
      did not influence the overall result, by confirming the increased risk of
      cardiovascular recurrences for patients with a poor response to clopidogrel
      treatment (OR 3.58, 95%CI 2.54 to 5.05; p<0.00001). The present updated meta
      analysis documents a significant association between residual platelet reactivity
      under clopidogrel treatment and recurrent cardiovascular events, so suggesting
      the relevance of ongoing interventional studies aimed at tailoring the
      antithrombotic therapy in CAD patients.

PMID- 20135064
TI  - Estrogen therapy for hereditary haemorrhagic telangiectasia (HHT): Effects of
      raloxifene, on Endoglin and ALK1 expression in endothelial cells.
AB  - Hereditary haemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is
      an autosomal dominant vascular disease. The clinical manifestations are
      epistaxis, mucocutaneous and gastrointestinal telangiectases, and arteriovenous
      malformations. There are two predominant types of HHT caused by mutations in
      Endoglin (ENG) and activin receptor-like kinase 1 (ALK1) (ACVRL1) genes, HHT1 and
      HHT2, respectively. No cure for HHT has been found and there is a current need to
      find new effective drug treatments for the disease. Some patients show severe
      epistaxis which interferes with their quality of life. We report preliminary
      results obtained with Raloxifene to treat epistaxis in postmenopausal HHT women
      diagnosed with osteoporosis. We tried to unravel the molecular mechanisms
      involved in the therapeutic effects of raloxifene. ENG and ACVRL1 genes code for
      proteins involved in the transforming growth factor beta pathway and it is widely
      accepted that haploinsufficiency is the origin for the pathogenicity of HHT.
      Therefore, identification of drugs able to increase the expression of those genes
      is essential to propose new therapies for HHT. In vitro results show that
      raloxifene increases the protein and mRNA expression of ENG and ALK1 in cultured
      endothelial cells. Raloxifene also stimulates the promoter activity of these
      genes, suggesting a transcriptional regulation of ENG and ALK1. Furthermore,
      Raloxifene improved endothelial cell functions like tubulogenesis and migration
      in agreement with the reported functional roles of Endoglin and ALK1. Our pilot
      study provides a further hint that oral administration of raloxifene may be
      beneficial for epistaxis treatment in HHT menopausal women. The molecular
      mechanisms of raloxifene involve counteracting the haploinsufficiency of ENG and
      ALK1.

PMID- 20135065
TI  - Neuroserpin, a thrombolytic serine protease inhibitor (serpin), blocks transplant
      vasculopathy with associated modification of T-helper cell subsets.
AB  - Thrombolytic serine proteases not only initiate fibrinolysis, but also are up
      regulated in vascular disease and acute inflammatory responses. Although the
      serine protease inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1) is
      considered a main regulator of thrombolysis, PAI-1 is also associated with
      vascular inflammation. The role of other serpins that target thrombolytic
      proteases, PAI-2, PAI-3, and neuroserpin (NSP), in vascular inflammation is,
      however, less well defined. NSP is a mammalian serpin that, similar to PAI-1,
      inhibits urokinase- and tissue-type plasminogen activators (uPA and tPA,
      respectively) and has been most closely associated with the nervous system, with
      a demonstrated protective role after cerebral infarction in mouse models.
      However, the role of NSP in systemic arterial inflammation and plaque growth is
      not known. Serp-1 is a myxoma viral serpin that also inhibits tPA and uPA, as
      well as additionally inhibiting plasmin and factor Xa (fXa). Serp-1 has proven
      highly potent anti-inflammatory and anti-atherogenic activity. Here we assess the
      effects of NSP treatment on plaque growth and T-helper (Th) lymphocyte activity
      in a mouse aortic allograft transplant model, with comparison to Serp-1. NSP and
      Serp-1 both significantly reduced plaque growth and T-cell invasion. T-bet (a Th1
      differentiation marker) was significantly reduced in transplanted aorta with
      associated reductions in Th1 and Th17, but not Th2, in splenocytes. NSP had
      additional Th modifying activity in non-transplanted mice. In summary, this is
      the first report that NSP possesses anti-inflammatory activity in systemic
      arteries, modifying Th cell responses and significantly reducing plaque growth in
      mouse aortic allografts.

PMID- 20135066
TI  - Platelet P2Y12 receptor antagonist pharmacokinetics and pharmacodynamics: A
      foundation for distinguishing mechanisms of bleeding and anticipated risk for
      platelet-directed therapies.
AB  - The platelet P2Y12 receptor is involved in all aspects of arterial thrombosis,
      including adhesion, activation, aggregation, secretion and development of a
      stable aggregate on which coagulation proteins can assemble and fibrin strands
      can mesh. Inhibition of the P2Y12 receptor has been shown convincingly to reduce
      cardiovascular events among patients with acute coronary syndromes (ACS) and in
      patients undergoing percutaneous intervention (PCI). Current studies are
      exploring whether there is a threshold of platelet aggregation below which only
      more bleeding occurs, without a concomitant reduction in clinical events. The
      following review considers the potential relevance of reversible and irreversible
      mechanisms of P2Y12 inhibition to bleeding risk, posing the question, "Is it not
      only how much but how a platelet P2Y12 receptor is inhibited that determines the
      attributable safety profile?"

PMID- 20135067
TI  - Prognostic value of plasma von Willebrand factor-cleaving protease (ADAMTS13)
      antigen levels in patients with coronary artery disease.
AB  - High plasma level of von Willebrand factor (VWF) is a marker of future
      cardiovascular events in patients at high risk of coronary artery disease (CAD).
      The purpose of this study was to examine the changes and the prognostic value of
      plasma VWF-cleaving protease (ADAMTS13) levels in patients with CAD. Plasma VWF
      and ADAMTS13 levels were measured in 225 patients with CAD (152 men and 73 women,
      age, 70.3 +/- 8.9 years, mean +/- SD) and 100 patients without CAD who were age-
      and gender-matched to the CAD patients (60 men and 40 women, age, 68.6 +/- 8.9
      years). The CAD patients had higher VWF and lower ADAMTS13 antigen levels
      compared to patients without CAD. During 22.3 +/- 10.4 months follow-up period,
      20 major adverse cardiac and cerebrovascular events (MACCE) occurred in 222
      patients with CAD who could be followed up. Kaplan-Meier analysis demonstrated
      that CAD patients with high plasma VWF antigen levels were significantly more
      likely to develop MACCE. Furthermore, eight cardiac and cerebrovascular
      thrombotic events [acute coronary syndrome (n=4) and cerebral infarction (n=4)]
      occurred in CAD patients with both high plasma VWF and low ADAMTS13 antigen
      levels. Multivariate Cox hazards regression analysis identified high plasma VWF
      and low ADAMTS13 antigen levels as significant and independent predictors of
      future MACCE and thrombotic events during the follow-up period in CAD patients.
      Our findings suggest that low plasma ADAMTS13 as well as high VWF level is a
      useful predictor of cardiac and cerebrovascular events in CAD patients.

PMID- 20135068
TI  - Constitutive and functionally relevant expression of JAM-C on platelets.

PMID- 20135069
TI  - Cellular and intracellular distribution of recombinant activated factor VII in
      the rat liver.

PMID- 20135070
TI  - In vitro effects of recombinant activated factor VIIa (NovoSeven) on clopidogrel
      induced platelet inhibition.

PMID- 20135071
TI  - Comparative efficacy and safety of the novel oral anticoagulants dabigatran,
      rivaroxaban and apixaban in preclinical and clinical development.
AB  - Therapeutic oral anticoagulation is still commonly achieved by administration of
      warfarin or other vitamin K antagonists that are associated with an untoward
      pharmacokinetic / pharmacodynamic (PK/PD) profile leading to a high incidence of
      bleeding complications or therapeutic failure. Hence, there is an unmet medical
      need of novel easy-to-use oral anticoagulants with improved efficacy and safety.
      Recent developments include the identification of non-peptidic small-molecules
      that selectively inhibit certain serine proteases within the coagulation cascade.
      Of these, the thrombin inhibitor dabigatran and factor Xa inhibitor rivaroxaban
      have recently been licensed for thromboprophylaxis after orthopaedic surgery
      mainly in Europe. In addition, the factor Xa inhibitor apixaban is in late-stage
      clinical development. Each drug is prescribed at fixed doses without the need of
      anticoagulant monitoring. Phase III trials in orthopaedic patients essentially
      resulted in non-inferior efficacy of dabigatran and superior efficacy of
      rivaroxaban over enoxaparin without any marked differences of drug safety, while
      apixaban data is still controversial. However, alterations of rivaroxaban and
      apixaban pharmacokinetics upon interactions with inhibitors and inducers of
      CYP3A4 or P-glycoprotein may complicate the use of these compounds in daily
      practice, whereas dabigatran elimination largely depends on renal function.
      Hence, this review reports PK/PD, efficacy and safety data of dabigatran,
      rivaroxaban and apixaban throughout preclinical and clinical development.

PMID- 20135073
TI  - Management of prekallikrein deficiency during cardiac surgery.

PMID- 20135074
TI  - A genetic variant in the gene encoding fibrinogen beta chain predicted
      development of hypertension in Chinese men.
AB  - Fibrinogen, a major determinant of blood viscosity, is an acute phase protein
      associated with cardiovascular disease. We studied the association of
      hypertension with single nucleotide polymorphisms (SNPs) in the gene encoding the
      fibrinogen beta chain (FGB). Three tagging SNPs (rs1025154, rs4220 and rs1044291)
      were selected from the HapMap database on Han Chinese. Genotypes were determined
      in 1,294 unrelated subjects from the Hong Kong Cardiovascular Risk Factor
      Prevalence Study cohort. There were 199 hypertensive subjects at baseline. Among
      1,095 subjects normotensive at baseline, 178 developed hypertension during a
      median follow-up period of 6.4 years. Among the three tagging SNPs, rs4220 showed
      significant association with hypertension at both baseline (odds ratio [OR]=1.49,
      p=0.004) and at follow-up (OR=1.32, p=0.013). The minor A allele of this SNP was
      associated with higher plasma fibrinogen level (beta=0.144, p<0.001 at baseline
      and beta=0.130, p<0.001 at follow-up). Among subjects normotensive at baseline,
      this SNP was also associated with the development of hypertension in men
      (OR=1.52, p=0.022), but not in women. The SNP rs4220 in FGB , which leads to the
      substitution of arginine by lysine at position 448, is independently associated
      with plasma fibrinogen level and hypertension in Hong Kong Chinese. This suggests
      a possible causal role of fibrinogen in hypertension development, especially in
      men.

PMID- 20135075
TI  - Long-term secondary prophylaxis with recombinant activated factor VII (rFVIIa) in
      haemophilia A with inhibitors: a case report.

PMID- 20135076
TI  - Nucleic acid aptamers as antithrombotic agents: Opportunities in extracellular
      therapeutics.
AB  - Antithrombotic therapy for the acute management of thrombotic disorders has been
      stimulated and guided actively by our current understanding of platelet biology,
      coagulation proteases, and vascular science. A translatable platform for
      coagulation, based soundly on biochemistry, enzymology and cellular events on
      platelets and tissue factor-baring cells, introduces fundamental constructs,
      mechanistic clarity, and an unparalleled opportunity for accelerating the
      development and clinical investigation of both disease- and patient-specific
      therapies. In the current review, we build upon and expand substantially our
      observations surrounding nucleic acids as antithrombotic agents.

PMID- 20135072
TI  - Venous thromboembolism risk and prophylaxis in hospitalised medically ill
      patients. The ENDORSE Global Survey.
AB  - Limited data are available regarding the risk for venous thromboembolism (VTE)
      and VTE prophylaxis use in hospitalised medically ill patients. We analysed data
      from the global ENDORSE survey to evaluate VTE risk and prophylaxis use in this
      population according to diagnosis, baseline characteristics, and country. Data on
      patient characteristics, VTE risk, and prophylaxis use were abstracted from
      hospital charts. VTE risk and prophylaxis use were evaluated according to the
      2004 American College of Chest Physicians (ACCP) guidelines. Multivariable
      analysis was performed to identify factors associated with use of ACCP
      recommended prophylaxis. Data were evaluated for 37,356 hospitalised medical
      patients across 32 countries. VTE risk varied according to medical diagnosis,
      from 31.2% of patients with gastrointestinal/hepatobiliary diseases to 100% of
      patients with acute heart failure, active non-infectious respiratory disease, or
      pulmonary infection (global rate, 41.5%). Among those at risk for VTE, ACCP
      recommended prophylaxis was used in 24.4% haemorrhagic stroke patients and 40-45%
      of cardiopulmonary disease patients (global rate, 39.5%). Large differences in
      prophylaxis use were observed among countries. Markers of disease severity,
      including central venous catheters, mechanical ventilation, and admission to
      intensive care units, were strongly associated with use of ACCP-recommended
      prophylaxis. In conclusion, VTE risk varies according to medical diagnosis. Less
      than 40% of at-risk hospitalised medical patients receive ACCP-recommended
      prophylaxis. Prophylaxis use appears to be associated with disease severity
      rather than medical diagnosis. These data support the necessity to improve
      implementation of available guidelines for evaluating VTE risk and providing
      prophylaxis to hospitalised medical patients.

PMID- 20135077
TI  - Antithrombotic treatment and the risk of death and stroke in patients with atrial
      fibrillation and a CHADS2 score=1.
AB  - In patients with atrial fibrillation (AF) and an intermediate risk of stroke
      (CHADS2 score =1), available evidence from clinical trials is inconclusive and
      the present guidelines for the management of AF indicate that the choice between
      oral anticoagulant and aspirin in these patients is open. Our goal was to
      evaluate whether, in patients with AF and only one moderate risk factor for
      thromboembolism, treatment with an oral anticoagulant is appreciably more
      beneficial than treatment with an antiplatelet agent. Among 6,517 unselected
      patients with AF, 1,012 of them (15.5%) had a CHADS2 score of 1 and were liable
      to treatment with an antiplatelet agent or an anticoagulant. An oral
      anticoagulant was prescribed for 606 patients (59.9%) and an antiplatelet agent
      or no antithrombotic treatment for 406 (40.1%). During follow-up (median=793
      days, interquartile range=1,332 days), 105 deaths (10.4%) and 19 strokes (1.9%)
      were recorded. The administration of an anticoagulant was associated with a lower
      rate of events (relative risk=0.42, 95% confidence interval 0.29-0.60, p<0.0001)
      than when no anticoagulant was prescribed. Results remained similar after
      adjustment for age and other confounding factors. In contrast, prescription of an
      antiplatelet agent was not associated with a lower risk of events. Factors
      independently associated with an increased risk of events were older age
      (p<0.0001), concomitant heart failure (p=0.0002), diabetes (p=0.0025), lack of
      prescription of an anticoagulant (p<0.0001) and permanent AF (p=0.04). Thus,
      prescription of an anticoagulant is independently associated with a decreased
      risk of death or stroke among patients with AF and a CHADS2 score =1.

PMID- 20135078
TI  - An experimental evaluation of boosting methods for classification.
AB  - OBJECTIVES: In clinical medicine, the accuracy achieved by classification rules
      is often not sufficient to justify their use in daily practice. In order to
      improve classifiers it has become popular to combine single classification rules
      into a classification ensemble. Two popular boosting methods will be compared
      with classical statistical approaches. METHODS: Using data from a clinical study
      on the diagnosis of breast tumors and by simulation we will compare AdaBoost with
      gradient boosting ensembles of regression trees. We will also consider a tree
      approach and logistic regression as traditional competitors. In logistic
      regression we allow to select non- linear effects by the fractional polynomial
      approach. Performance of the classifiers will be assessed by estimated
      misclassification rates and the Brier score. RESULTS: We will show that boosting
      of simple base classifiers gives classification rules with improved predictive
      ability. However, the performance of boosting classifiers was not generally
      superior to the performance of logistic regression. In contrast to the computer
      intensive methods the latter are based on classifiers which are much easier to
      interpret and to use. CONCLUSIONS: In medical applications, the logistic
      regression model remains a method of choice or, at least, a serious competitor of
      more sophisticated techniques. Refinement of boosting methods by using optimized
      number of boosting steps may lead to further improvement.

PMID- 20135079
TI  - Correlation-based gene selection and classification using Taguchi-BPSO.
AB  - BACKGROUND: Microarray data with reference to gene expression profiles have
      provided some valuable results related to a variety of problems, and contributed
      to advances in clinical medicine. Microarray data characteristically have a high
      dimension and small sample size, which makes it difficult for a general
      classification method to obtain correct data for classification. However, not
      every gene is potentially relevant for distinguishing the sample class. Thus, in
      order to analyze gene expression profiles correctly, feature (gene) selection is
      crucial for the classification process, and an effective gene extraction method
      is necessary for eliminating irrelevant genes and decreasing the classification
      error rate. OBJECTIVE: The purpose of gene expression analysis is to discriminate
      between classes of samples, and to predict the relative importance of each gene
      for sample classification. METHOD: In this paper, correlation-based feature
      selection (CFS) and Taguchi-binary particle swarm optimization (TBPSO) were
      combined into a hybrid method, and the K-nearest neighbor (K-NN) with leave-one
      out cross-validation (LOOCV) method served as a classifier for ten gene
      expression profiles. RESULTS: Experimental results show that this hybrid method
      effectively simplifies feature selection by reducing the number of features
      needed. The classification error rate obtained by the proposed method had the
      lowest classification error rate for all of the ten gene expression data set
      problems tested. For six of the gene expression profile data sets a
      classification error rate of zero could be reached. CONCLUSION: The introduced
      method outperformed five other methods from the literature in terms of
      classification error rate. It could thus constitute a valuable tool for gene
      expression analysis in future studies.

PMID- 20135080
TI  - Putting biomedical ontologies to work.
AB  - OBJECTIVES: Biomedical ontologies exist to serve integration of clinical and
      experimental data, and it is critical to their success that they be put to
      widespread use in the annotation of data. How, then, can ontologies achieve the
      sort of user-friendliness, reliability, cost-effectiveness, and breadth of
      coverage that is necessary to ensure extensive usage? METHODS: Our focus here is
      on two different sets of answers to these questions that have been proposed, on
      the one hand in medicine, by the SNOMED CT community, and on the other hand in
      biology, by the OBO Foundry. We address more specifically the issue as to how
      adherence to certain development principles can advance the usability and
      effectiveness of an ontology or terminology resource, for example by allowing
      more accurate maintenance, more reliable application, and more efficient
      interoperation with other ontologies and information resources. RESULTS: SNOMED
      CT and the OBO Foundry differ considerably in their general approach.
      Nevertheless, a general trend towards more formal rigor and cross-domain
      interoperability can be seen in both and we argue that this trend should be
      accepted by all similar initiatives in the future. CONCLUSIONS: Future efforts in
      ontology development have to address the need for harmonization and integration
      of ontologies across disciplinary borders, and for this, coherent formalization
      of ontologies is a pre-requisite.

PMID- 20135081
TI  - Semantic interoperability adheres to proper models and code systems. A detailed
      examination of different approaches for score systems.
AB  - OBJECTIVES: Achieving semantic interoperability requires not only the use of
      communication standards like HL7 with its underlying models and specifications,
      but also to constrain those models to instances including permitted attributes,
      data types, values and code systems. Even the application of both strategies may
      lead to different modeling approaches and therefore incompatible results,
      however. METHODS: This paper analyzes the different ways to create a model
      exemplified at score and assessment systems. RESULTS: The different approaches
      have advantages and disadvantages. The presented results allow for transmitting
      the same basic information facilitating HL7 v2.x and V3 in a way reducing
      implementation efforts. CONCLUSIONS: Establishing a generic approach to
      communicate the details of score systems driven by an appropriate set of codes is
      the best solution for implementers.

PMID- 20135082
TI  - Ensuring the continuity of care of cardiorespiratory diseases at home. Monitoring
      equipment and medical data exchange over semantically annotated web services.
AB  - OBJECTIVES: A significant portion of care related to cardiorespiratory diseases
      is provided at home, usually but not exclusively, after the discharge of a
      patient from hospital. It is the purpose of the present study to present the
      technical means which we have developed, in order to support the adaptation of
      the continuity of care of cardiorespiratory diseases at home. METHODS: We have
      developed an integrated system that includes: first, a prototype laptop-based
      portable monitoring system that comprises low-cost commercially available
      components, which enable the periodical or continuous monitoring of vital signs
      at home; second, software supporting medical decision-making related to
      tachycardia and ventricular fibrillation, as well as fuzzy-rules-based software
      supporting home-ventilation optimization; third, a typical continuity of care
      record (CCR) adapted to support also the creation of a homecare plan; and
      finally, a prototype ontology, based upon the HL7 clinical document architecture
      (CDA), serving as basis for the development of semantically annotated web
      services that allow for the exchange and retrieval of homecare information.
      RESULTS: The flexible design and the adaptable data-exchange mechanism of the
      developed system result in a useful and standard-compliant tool, for
      cardiorespiratory disease-related homecare. CONCLUSIONS: The ongoing laboratory
      testing of the system shows that it is able to contribute to an effective and low
      cost package solution, supporting patient supervision and treatment. Furthermore,
      semantic web technologies prove to be the perfect solution for both the
      conceptualization of a continuity of care data exchange procedure and for the
      integration of the structured medical data.

PMID- 20135083
TI  - Architectural approach to eHealth for enabling paradigm changes in health.
AB  - OBJECTIVES: For improving safety and quality of care as well as efficiency of
      health delivery under the well-known burdens, health services become specialized,
      distributed, and therefore collaborative, thereby changing the health service
      paradigm from organization-centered over process-controlled to personal health
      (pHealth). METHODS: Personalized eHealth services provided independent of time
      and location have to be based on advanced technical paradigms of mobile,
      pervasive and autonomous computing, enabling ubiquitous health services.
      Personalized eHealth systems require a multidisciplinary approach including
      medicine, informatics, biomedical engineering, bioinformatics and the omics
      disciplines but also legal and regulatory affairs, administration, security,
      privacy and ethics, etc. Interoperability between different components of the
      intended system must be provided through an architecture-centric, model-driven,
      formalized process. RESULTS: In order to analyze, design, specify, implement and
      maintain such an interactive environment impacted by so many different domains, a
      formal and unified methodology for system analysis and design has been developed
      and deployed, based on an overall architectural framework. The paper introduces
      the underlying paradigms, requirements, architectural reference models, modeling
      and formalization principles as well as development processes for comprehensive
      service-oriented personalized eHealth interoperability chains, thereby exploiting
      all interoperability levels up to service interoperability. A special focus is
      put on ontologies and knowledge representation in the context of eHealth and
      pHealth solutions. Furthermore, EHR solutions, security requirements, existing
      and emerging standards, and educational challenges for realizing personalized
      pHealth are briefly discussed. CONCLUSION: For personal health, bridging between
      disciplines including ontology coordination is the crucial demand. All aspects of
      the design and development process have to be considered from an architectural
      viewpoint.

PMID- 20135084
TI  - [Anesthesia in patients with anorexia nervosa and bulimia nervosa].
AB  - Eating disorders are typical diseases of adolescence and early adulthood. About 1
      3% of female juveniles suffer from anorexia nervosa (AN) or bulimia nervosa (BN).
      Today AN is still the psychiatric disease with the highest mortality rate. The
      peri-operative mortality rate of patients suffering from AN is in the range up to
      15%. The beginning of AN is a lingering process and the majority of patients show
      increasingly restrictive eating habits ending in cachexia. Patients are obsessed
      by the predominant idea of being obese in spite of having a significant
      underweight. Patients suffering from bulimia break the strict regimen by eating
      enormous amounts of high calorie food. Such eating attacks are followed by weight
      reducing measures, mostly vomiting. Most of the physical changes caused by AN are
      due to starvation and loss of weight. The most significant medical complications
      are alterations of the cardiovascular system accompanied by decreasing
      contractility of the heart, bradycardia, electrocardiographic changes as well as
      disequilibrium of electrolytic and water balance. Most of these symptoms can be
      reversed by putting on weight.

PMID- 20135085
TI  - [Alpha1-antitrypsin deficiency].
AB  - Alpha(1)-antitrypsin deficiency is characterized by a pathologic reduction of the
      serum concentration of alpha(1)-antitrypsin, the most important antiprotease in
      man. It is one of the most common hereditary diseases in Caucasians.
      Approximately 2% of obstructive airway diseases are caused by alpha(1)
      antitrypsin deficiency. Patients above 35 years may develop lung emphysema,
      especially in the lower lobes. Symptoms are those of chronic obstructive
      pulmonary disease such as cough, sputum expectoration, and progressive dyspnoea.
      Patients with homozygous defect often develop cholestatic hepatitis in the
      neonatal period. However, only few adult patients develop chronic liver disease
      up to liver cirrhosis with an elevated risk for malignant liver tumors. The
      diagnostic hallmark is the reduced serum concentration of alpha(1)-antitrypsin
      while genetic testing proves the defect. An early recognition of the disease is
      decisive for prophylactic and therapeutic measures. Smoking should be stopped
      immediately. Treatment of lung disease includes physiotherapy, antiobstructive
      and antiinflammatory medication, augmentation with human alpha(1)-antitrypsin and
      lung surgery including lung transplantation. Liver toxins should be avoided.
      Besides experimental therapeutic approaches, liver disease can only be treated by
      liver transplantation.

PMID- 20135086
TI  - [Endoscopic palliation of esophageal and bronchial carcinomas].
AB  - Luminal obstruction from tumor growth can in relation to bronchial carcinoma lead
      to airway and/or esophageal obstruction in breathlessness or swallowing
      difficulties respectively. Self-expanding stents have become an established
      method of restoring luminal patency in both the esophagus and central airways,
      leading to significant symptomatic improvement. Due to anatomical constraints
      particularly in processes around the tracheal carina, stent implantation within
      the bronchial system often poses greater difficulty than within the esophagus.
      Technical difficulties do however arise in the esophagus, specifically in
      relation to stenotic high-cervical tumors, as well as distal stenosis. In this
      regard, advances in stent development have resulted in significantly improved
      outcomes with modern stents. In high-cervical esophageal tumors as well as
      locally invasive tumors with evidence of tracheobronchial fistulae a shared
      interdisciplinary care between the gastroenterology and pulmonary teams is
      necessary for a satisfactory outcome.

PMID- 20135087
TI  - Where do the leukaemia relapses come from?

PMID- 20135088
TI  - Assessing the cost-effectiveness of drug and lifestyle intervention following
      opportunistic screening for pre-diabetes in primary care.
AB  - AIMS/HYPOTHESIS: This study aims to evaluate the cost-effectiveness of a
      screening programme for pre-diabetes, which was followed up by treatment with
      pharmaceutical interventions (acarbose, metformin, orlistat) or lifestyle
      interventions (diet, exercise, diet and exercise) in order to prevent or slow the
      onset of diabetes in those at high risk. METHODS: To approximate the experience
      of individuals with pre-diabetes in the Australian population, we used a
      microsimulation approach, following patient progression through diabetes,
      cardiovascular disease and renal failure. The model compares costs and disability
      adjusted life years lived in people identified through an opportunistic screening
      programme for each intervention compared with a 'do nothing' scenario, which is
      representative of current practice. It is assumed that the effect of a lifestyle
      change will decay by 10% per year, while the effect of a pharmaceutical
      intervention remains constant throughout use. RESULTS: The most cost-effective
      intervention options are diet and exercise combined, with a cost-effectiveness
      ratio of AUD 22,500 per disability-adjusted life year (DALY) averted, and
      metformin with a cost-effectiveness ratio of AUD 21,500 per DALY averted. The
      incremental addition of one intervention to the other is not cost-effective.
      CONCLUSIONS/INTERPRETATION: Screening for pre-diabetes followed by diet and
      exercise, or metformin treatment is cost-effective and should be considered for
      incorporation into current practice. The number of dietitians and exercise
      physiologists needed to deliver such lifestyle change interventions will need to
      be increased to appropriately support the intervention.

PMID- 20135089
TI  - The relationship of comorbidity of mental and substance use disorders with
      suicidal behaviors in the Nigerian Survey of Mental Health and Wellbeing.
AB  - BACKGROUND: Mental and substance use disorders are often associated with an
      elevated risk for suicidal behaviors. The role of the co-occurrence of multiple
      disorders in this association is still unclear. METHOD: The Nigerian Survey of
      Mental Health and Wellbeing is a community survey of mental and substance use
      disorders as well as of suicidal outcomes. Face-to-face assessment was conducted
      using the World Health Organization's Composite International Diagnostic
      Interview, version 3. A total of 6,752 adults, aged 18 years and over, were
      interviewed. RESULTS: Persons with lifetime suicide attempt were more likely than
      those without attempt to have experienced lifetime DSM-IV disorders. Lifetime
      attempters were also more likely to have comorbid conditions. Compared with only
      0.4% of persons with no history of lifetime attempts, over 11% of persons with
      lifetime attempt had three or more co-occurring disorders. Multivariate analysis
      controlling for the effects of comorbid conditions suggests that while mood
      disorder is independently associated with suicidal outcomes, comorbidity partly
      explains the association of anxiety disorders and almost fully accounts for the
      association of substance use disorders with suicidal outcomes. CONCLUSION:
      Comorbidity is an important factor in the association of mental and substance use
      disorders with suicidal behavior.

PMID- 20135090
TI  - Recommendations for intensive care unit and hospital preparations for an
      influenza epidemic or mass disaster: summary report of the European Society of
      Intensive Care Medicine's Task Force for intensive care unit triage during an
      influenza epidemic or mass disaster.
AB  - PURPOSE: To provide recommendations and standard operating procedures for
      intensive care units and hospital preparedness for an influenza pandemic.
      METHODS: Based on a literature review and expert opinion, a Delphi process was
      used to define the essential topics. RESULTS: Key recommendations include:
      Hospitals should increase their ICU beds to the maximal extent by expanding ICU
      capacity and expanding ICUs into other areas. Hospitals should have appropriate
      beds and monitors for these expansion areas. Establish a management system with
      control groups at facility, local, regional and/or national levels to exercise
      authority over resources. Establish a system of communication, coordination and
      collaboration between the ICU and key interface departments. A plan to access,
      coordinate and increase labor resources is required with a central inventory of
      all clinical and non-clinical staff. Delegate duties not within the usual scope
      of workers' practice. Ensure that adequate essential medical equipment,
      pharmaceuticals and supplies are available. Protect patients and staff with
      infection control practices and supporting occupational health policies. Maintain
      staff confidence with reassurance plans for legal protection and assistance. Have
      objective, ethical, transparent triage criteria that are applied equitably and
      publically disclosed. ICU triage of patients should be based on the likelihood
      for patients to benefit most or a 'first come, first served' basis. Develop
      protocols for safe performance of high-risk procedures. Train and educate staff.
      CONCLUSIONS: Mortality, although inevitable during a severe influenza outbreak or
      disaster, can be reduced by adequate preparation.

PMID- 20135092
TI  - Reduced cortical bone density with normal trabecular bone density in girls with
      Turner syndrome.
AB  - SUMMARY: This study of 22 girls with Turner syndrome (TS) demonstrates a
      reduction in bone mineral apparent density (BMAD) at the femoral neck along with
      a reduction in cortical bone density at the radius (with sparing of trabecular
      bone). These findings may account for the increased fracture risk noted in this
      population. INTRODUCTION: Increased fracture risk is a feature of TS; however,
      the reasons for this are unclear. Little is known regarding cortical and
      trabecular bone mineral density (BMD) in TS. We have addressed this by
      measurement of volumetric bone mineral density (vBMD) using peripheral
      quantitative computed tomography (pQCT). METHODS: We studied 22 females with TS
      and 21 females without TS; mean ages 12.7 and 12.9 years, respectively. Bone mass
      measurements were made by dual-energy X-ray absorptiometry (DXA) of the lumbar
      spine and femur and pQCT of the radius. BMAD was calculated from DXA values. We
      utilized published reference data to generate Z-scores for both populations.
      RESULTS: The mean BMAD Z-score at the lumbar spine was not significantly
      different in individuals with TS compared to the controls. At the femoral neck,
      individuals with TS had a significantly lower BMAD Z-score compared to the
      controls (-1.32 vs. -0.14, p = 0.001). At the distal radius, total vBMD Z-score
      and trabecular vBMD Z-score were not significantly different between the TS group
      and controls. A significant reduction in cortical vBMD at the proximal radius was
      noted in the TS group however (-2.58 vs. -1.38, p = 0.02). There was also a trend
      towards reduced cortical thickness at this site in the TS group (Z-score -2.89
      vs. -1.73, p = 0.08). DISCUSSION: TS is associated with reduced BMAD at the
      femoral neck; pQCT data suggests that cortical density is reduced with sparing of
      trabecular bone. This differential of cortical and trabecular BMD may predispose
      to fracture.

PMID- 20135093
TI  - Detection of vertebral fractures in DXA VFA images using statistical models of
      appearance and a semi-automatic segmentation.
AB  - SUMMARY: Morphometric methods of vertebral fracture diagnosis lack specificity.
      We used detailed shape and image texture model parameters to improve the
      specificity of quantitative fracture identification. Two radiologists visually
      classified all vertebrae for system training and evaluation. The vertebral
      endplates were located by a semi-automatic segmentation method to obtain
      classifier inputs. INTRODUCTION: Vertebral fractures are common osteoporotic
      fractures, but current quantitative detection methods (morphometry) lack
      specificity. We used detailed shape and texture information to develop more
      specific quantitative classifiers of vertebral fracture to improve the
      objectivity of vertebral fracture diagnosis. These classifiers require a detailed
      segmentation of the vertebral endplate, and so we investigated the use of semi
      automated segmentation methods as part of the diagnosis. METHODS: The vertebrae
      in a training set of 360 dual energy X-ray absorptiometry images were manually
      segmented. The shape and image texture of vertebrae were statistically modelled
      using Appearance Models. The vertebrae were given a gold standard classification
      by two radiologists. Linear discriminant classifiers to detect fractures were
      trained on the vertebral appearance model parameters. Classifier performance was
      evaluated by cross-validation for manual and semi-automatic segmentations, the
      latter derived using Active Appearance Models (AAM). Results were compared with a
      morphometric algorithm using the signs test. RESULTS: With manual segmentation,
      the false positive rates (FPR) at 95% sensitivity were: 5% (appearance) and 18%
      (morphometry). With semi-automatic segmentations the sensitivities at 5% FPR
      were: 88% (appearance) and 79% (morphometry). CONCLUSION: Specificity and
      sensitivity are improved by using an appearance-based classifier compared to
      standard height ratio morphometry. An overall sensitivity loss of 7% occurs (at
      95% specificity) when using a semi-automatic (AAM) segmentation compared to
      expert annotation, due to segmentation error. However, the classifier sensitivity
      is still adequate for a computer-assisted diagnosis system for vertebral
      fracture, especially if used in a triage approach.

PMID- 20135094
TI  - Histomorphometric changes by teriparatide in alendronate-pretreated women with
      osteoporosis.
AB  - SUMMARY: The level of increased bone formation after 24 months of treatment with
      teriparatide (rhPTH (1-34), TPTD) is similar in patients who were either
      treatment-naive (TN) or had lower bone turnover initially due to previous
      alendronate (ALN) therapy. INTRODUCTION: Bone anabolic effects of TPTD in
      postmenopausal women with osteoporosis may be blunted during the initial phase
      after switching from ALN to TPTD. To explore the long-term implications, we
      examined histomorphometric and biochemical markers of bone turnover of patients
      on TPTD therapy after long-term ALN treatment. METHODS: Paired biopsies were
      obtained after tetracycline double labeling at baseline and after 24 months of
      TPTD treatment from 29 ALN-pretreated (64.5 +/- 16.4 months) and 16 TN patients.
      Biochemical markers were measured at baseline, during the treatment, or at study
      end. RESULTS: Compared with the baseline, after 24-month TPTD, activation
      frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11-0.34
      cycles per year, 3.96-9.8% in the ALN-pretreated group and 0.19-0.33 cycles per
      year, 6.2-11.3% (p < 0.05) in the TN group, respectively. Biochemical and
      histomorphometric markers correlated positively both at baseline and endpoint.
      Serum amino terminal propeptide of type I procollagen (PINP) correlated with
      Ac.F. (r = 0.57, p < 0.001 and r = 0.48, p < 0.01) and OS (r = 0.51, p < 0.01 and
      r = 0.56, p < 0.01) at baseline and endpoint, respectively. Following 3 months of
      treatment, increases in biochemical markers like PINP predicted the increase in
      Ac.F. (r = 0.52, p < 0.01) and OS (r = 0.54, p < 0.01) after 24 months.
      CONCLUSIONS: The increased level of formation is similar in patients who were
      either TN or had lower bone turnover initially due to previous ALN therapy.
      Elevated bone formation in postmenopausal women with osteoporosis was sustained
      over a 24-month period by TPTD. Biochemical markers of bone formation are a good
      surrogate for the assessment of TPTD effects.

PMID- 20135095
TI  - Does using lower limit of normal values enhance the ability of a single bone
      mineral density measure to predict fractures?
AB  - Using a single bone mineral density (BMD) measure, we demonstrated that the lower
      limit of normal (LLN) method is more consistent in predicting osteoporosis
      fractures than the T-score in white menopausal women from the Study of
      Osteoporosis Fracture (SOF). INTRODUCTION: In order to circumvent the
      inconsistencies and limitations with using the T-score when defining
      osteoporosis, we propose using 95% LLN values derived from centered polynomial
      models using the NHANES III BMD measures. The main aim of this study was to
      compare the two methods in prediction of fracture and agreement in osteoporosis
      classification using cohort data. METHODS: We compared the fracture prediction
      ability of the two methods using a single BMD measurement in 4,948 white women
      aged 67-74 years in the SOF employing kappa statistics, sensitivity, and
      specificity. RESULTS: The T-score provided inconsistent osteoporosis
      classification (46.6%) across the five hip regions of interest (ROIs) and this
      was significantly (p<0.0001) reduced when using the LLN method (36.5%). Kappa
      statistics of incident fracture during 12 years of follow-up related to the
      prevalence of osteoporosis at baseline was significantly improved using the LLN
      method compared to using T-score. Sensitivity and specificity for fracture based
      on a single BMD measurement of different hip ROIs were more consistent using the
      LLN method. CONCLUSION: The LLN method provides a more consistent and efficient
      method for osteoporosis fracture prediction than the T-score in 67- to 74-year
      old white women.

PMID- 20135096
TI  - Reduced tibial speed of sound in Chinese infants at birth compared with Caucasian
      peers: the effects of race, gender, and vitamin D on fetal bone development.
AB  - SUMMARY: This study compared bone status between Chinese and Caucasian infants at
      birth, showing that Chinese neonates have lower tibial speed of sound, which is
      influenced by gender, gestational age, season of birth, and maternal vitamin D
      status. The effects of these factors on fetal bone development were discussed.
      INTRODUCTION: We compared the differences of speed of sound (SOS) accessed by
      quantitative ultrasound between Chinese and Caucasian infants at birth and
      explored the relationship between the concentrations of serum 25-hydroxyvitamin D
      [25(OH)D] and bone SOS in maternal-infant pairs. METHODS: SOS for the tibial bone
      was measured at birth in 267 Chinese infants. We used the Z-scores for the direct
      comparisons which were available from the instrument based data of gender and age
      matched Caucasian peers. The concentrations of serum 25(OH)D and bone SOS in 32
      maternal-infant pairs were measured at birth in winters. RESULTS: the Chinese
      infants had lower SOS demonstrated by the Z-scores. Significant differences of
      SOS and Z-scores were found between genders, gestational ages, birth weight, and
      seasons of birth. The differences of Z-scores negatively decreased with
      gestational age, suggesting that the bone status of Chinese infants lags behind
      that of the Caucasian infants during the last trimester of pregnancy in utero.
      The tibial SOS of infants born in winters was 2.0% higher than those born in
      summers after adjustment. The infant SOS correlated with maternal serum 25(OH)D
      (r = 0.399, P = 0.024) and infant serum 25(OH)D (r = 0.394, P = 0.026).
      CONCLUSIONS: Chinese neonates have lower SOS which is influenced by gender,
      gestational age, season of birth, and maternal vitamin D status. It is inferred
      that, in pace with gestational age, race and gender effects on fetal bone
      development are modified by materno-fetal vitamin D status.

PMID- 20135097
TI  - Effects of bone mineral density of the lumbar spine and prevalent vertebral
      fractures on the risk of immobility.
AB  - SUMMARY: To clarify the contribution of osteoporosis to future immobilization, a
      prospective observational study was carried out on Japanese postmenopausal women.
      The prevalence of low bone mineral density (BMD) and vertebral fracture were
      independent risks for future immobilization. INTRODUCTION: Immobilization by hip
      fracture requires more medical care and higher costs. Osteoporosis increases the
      risk of hip fracture, but there is little data linking osteoporosis and
      immobilization in postmenopausal Japanese women. METHODS: The study participants
      consisted of postmenopausal ambulatory volunteers. Baseline information such as
      BMD, prevalent fractures, comorbidities, pain in the body, and variables were
      obtained from 1993, and time course of occurrence of immobilization was observed
      until 2008. RESULTS: A total of 1,312 participants were enrolled and were
      observed for a total of 6.7 +/- 4.1 years. A total of 75 subjects suffered
      immobilization. In multivariate analysis to calculate the Cox's hazard ratio of
      baseline parameters for immobilization, four independent variables were observed:
      age (hazard ratio, 1.52 [95% CI, 1.29 to 1.80], p = 0.000), pain in the body
      (2.54 [1.42 to 4.89, p = 0.001]), low BMD (1.83 [1.10 to 3.13, p = 0.020]), and
      dementia (3.58 [91.80 to 6.76, p = 0.001]). The hazard ratio of prevalent
      vertebral fracture was 1.98 (1.20 to 3.30, p = 0.007) instead of low BMD of above
      model. CONCLUSION: These results indicate that low BMD and prevalent vertebral
      fracture pose an independent risk for future immobilization in postmenopausal
      Japanese women.

PMID- 20135098
TI  - MRP transporters as membrane machinery in the bradykinin-inducible export of ATP.
AB  - Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal
      molecule in a variety of cells. So far, however, the membrane machinery in the
      export of intracellular ATP remains poorly understood. Activation of B2-receptor
      with bradykinin-induced massive release of ATP from cultured taenia coli smooth
      muscle cells. The evoked release of ATP was unaffected by gap junction
      hemichannel blockers, such as 18alpha-glycyrrhetinic acid and Gap 26.
      Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl(-)
      channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid,
      Gd3(+) and glibenclamide, failed to suppress the export of ATP by bradykinin. On
      the other, the evoked release of ATP was greatly reduced by multidrug resistance
      protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone.
      From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and
      MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not
      enhanced after loading with 1 muM bradykinin for 5 min. Likewise, niflumic acid
      and fulfenamic acid, Ca2(+)-activated Cl(-) channel blockers, largely abated the
      evoked release of ATP. The possibility that the MRP transporter system couples
      with Ca2(+)-activated Cl(-) channel activities is discussed here. These findings
      suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl(-) channels and gap
      junction hemichannels, may contribute as membrane machinery to the export of ATP
      induced by G-protein-coupled receptor stimulation.

PMID- 20135099
TI  - Timing of anticipatory muscle tensing control: responses before and after
      expected impact.
AB  - It is widely accepted that human motor control is anticipatory in nature.
      Previous studies have used electromyography (EMG) to examine muscle responses to
      falling objects and identified anticipatory muscle tensing (AMT) as a spike in
      activation that occurs prior to object impact. Some studies have suggested that
      humans use an internal model of gravity to mediate precisely timed AMT responses.
      The present study further examines predictive motor control through the analysis
      of AMT during an object catching task. For some trials, participants watched an
      object falling toward the hand; for other trials, their eyes were closed. For
      some trials, the object fell downward and impacted the hand; for other randomly
      selected trials, the object abruptly stopped 12 cm above the hand, enabling an
      assessment of the effect of impact anticipation independent of the reflexive
      tactile response associated with an actual impact. In Experiment 1, AMT did not
      shift for approximately 113 ms after the abrupt stop of the ball. In Experiment
      2, we randomly varied the start height of the object and found well-timed AMT
      with a 129-ms lag time. A control system based on simple memory for fall time
      duration cannot explain these findings. We argue that an AMT control system with
      a lag time of approximately 121 ms could not perform with human levels of
      accuracy without accounting for the acceleration of downward moving objects.

PMID- 20135100
TI  - Locomotor function after long-duration space flight: effects and motor learning
      during recovery.
AB  - Astronauts returning from space flight and performing Earth-bound activities must
      rapidly transition from the microgravity-adapted sensorimotor state to that of
      Earth's gravity. The goal of the current study was to assess locomotor
      dysfunction and recovery of function after long-duration space flight using a
      test of functional mobility. Eighteen International Space Station crewmembers
      experiencing an average flight duration of 185 days performed the functional
      mobility test (FMT) pre-flight and post-flight. To perform the FMT, subjects
      walked at a self selected pace through an obstacle course consisting of several
      pylons and obstacles set up on a base of 10-cm-thick, medium-density foam for a
      total of six trials per test session. The primary outcome measure was the time to
      complete the course (TCC, in seconds). To assess the long-term recovery trend of
      locomotor function after return from space flight, a multilevel exponential
      recovery model was fitted to the log-transformed TCC data. All crewmembers
      exhibited altered locomotor function after space flight, with a median 48%
      increase in the TCC. From the fitted model we calculated that a typical subject
      would recover to 95% of his/her pre-flight level at approximately 15 days post
      flight. In addition, to assess the early motor learning responses after returning
      from space flight, we modeled performance over the six trials during the first
      post-flight session by a similar multilevel exponential relation. We found a
      significant positive correlation between measures of long-term recovery and early
      motor learning (P < 0.001) obtained from the respective models. We concluded that
      two types of recovery processes influence an astronaut's ability to re-adapt to
      Earth's gravity environment. Early motor learning helps astronauts make rapid
      modifications in their motor control strategies during the first hours after
      landing. Further, this early motor learning appears to reinforce the adaptive
      realignment, facilitating re-adaptation to Earth's 1-g environment on return from
      space flight.

PMID- 20135101
TI  - Sex-related differences in the hemispheric laterality of slow cortical potentials
      during the preparation of visually guided movements.
AB  - Previous work suggests the presence of sex differences in the laterality of brain
      activity in the premotor-parietal network during the preparation of visually
      guided reaching movements. In the current study, electroencephalography was used
      to test the hypothesis that women would have higher amplitude potentials over
      frontal and parietal regions ipsilateral to arm movements, relative to men. Event
      related slow cortical potentials (SCPs) were collected from 30 participants (15
      men and 15 women) during the performance of two visually guided reaching
      conditions (eyes and arm moved to the same spatial location or moved in opposite
      directions). The results of the study demonstrate that the amplitudes of SCPs
      were significantly higher overlying frontal regions of the right hemisphere of
      women relative to men. These differences were present both during an instructed
      delay period prior to receiving a go-signal to initiate movement and during the
      period just prior to movement initiation. The study also revealed an interaction
      of Sex and Condition in the parietal region during the pre-movement period. These
      results suggest that motor preparatory activity in men mainly occurs in the
      hemisphere contralateral to reaching but that preparatory activity in women is
      distributed relatively more bilaterally. However, the nature of these differences
      changes over the time course of the preparatory period and is partially dependent
      on the type of visuomotor mapping being performed.

PMID- 20135102
TI  - Can intention override the "automatic pilot"?
AB  - Previous research has suggested that the visuomotor system possesses an
      "automatic pilot" which allows people to make rapid online movement corrections
      in response to sudden changes in target position. Importantly, the automatic
      pilot has been shown to operate in the absence of visual awareness, and even
      under circumstances in which people are explicitly asked not to correct their
      ongoing movement. In the current study, we investigated the extent to which the
      automatic pilot could be "disengaged" by explicitly instructing participants to
      ignore the target jump (i.e., "NO-GO"), by manipulating the order in which the
      two tasks were completed (i.e., either "GO" or NO-GO first), and by manipulating
      the proportion of trials in which the target jumped. The results indicated that
      participants made fewer corrections in response to the target jump when they were
      asked not to correct their movement (i.e., NO-GO), and when they completed the NO
      GO task prior to the task in which they were asked to correct their movement when
      the target jumped (i.e., the GO task). However, increasing the proportion of
      jumping targets had only a minimal influence on performance. Critically,
      participants still made a significant number of unintended corrections (i.e.,
      errors) in the NO-GO tasks, even under explicit instructions not to correct their
      movement if the target jumped. Overall these data suggest that, while the
      automatic pilot can be influenced to some degree by top-down strategies and
      previous experience, the pre-potent response to correct an ongoing movement
      cannot be completely disengaged.

PMID- 20135103
TI  - A simple method for the reconstitution of membrane proteins into giant
      unilamellar vesicles.
AB  - A simple method for the reconstitution of membrane protein from submicron
      proteoliposomes into giant unilamellar vesicles (GUVs) is presented here: This
      method does not require detergents, fusion peptides or a dehydration step of the
      membrane protein solution. In a first step, GUVs of lipids were formed by
      electroformation, purified and concentrated; and in a second step, the
      concentrated GUV solution was added to a small volume of vesicles or
      proteoliposomes. Material transfer from submicron vesicles and proteoliposomes to
      GUVs occurred spontaneously and was characterized with fluorescent microscopy and
      patch-clamp recordings. As a functional test, the voltage-dependent, anion
      selective channel protein was reconstituted into GUVs, and its
      electrophysiological activity was monitored with the patch clamp. This method is
      versatile since it is independent of the presence of the protein, as demonstrated
      by the fusion of fluorescently labeled submicron vesicles and proteoliposomes
      with GUVs.

PMID- 20135104
TI  - Long-term adaptation of Bacillus subtilis 168 to extreme pH affects chemical and
      physical properties of the cellular membrane.
AB  - We characterized physical and chemical properties of cell-membrane fragments from
      Bacillus subtilis 168 (trpC2) grown at pH 5.0, 7.0 and 8.5. Effects of long-term
      bacterial adaptation reflected in growth rates and in changes of the membrane
      lipid composition were correlated with lipid order and dynamics using time
      resolved fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene. We demonstrate
      that the pH adaptation results in a modification of a fatty acid content of
      cellular membranes that significantly influences both the lipid-chain order and
      dynamics. For cultivation at acidic conditions, the lipid order increases and
      membrane dynamics decreases compared to pH 7.0. This results in rigid and ordered
      membranes. Cultivation at pH 8.5 causes slight membrane disordering. Instant pH
      changes induce qualitatively similar but smaller effects. Proton flux
      measurements performed on intact cells adapted to both pH 5.0 and 8.5 revealed
      lower cell-membrane permeability compared to bacteria cultivated at pH optimum.
      Our results indicate that both acidic and alkalic pH stress represent a permanent
      challenge for B. subtilis to keep a functional membrane state. The documented
      adaptation-induced adjustments of membrane properties could be an important part
      of mechanisms maintaining an optimal intracellular pH at a wide range of
      extracellular proton concentrations.

PMID- 20135105
TI  - A deviant genetic code in the reduced mitochondrial genome of the picoplanktonic
      green alga Pycnococcus provasolii.
AB  - Reduction in size of flagellated chlorophytes occurred multiple times during
      evolution, providing the opportunity to study the consequences of cell reduction
      on genome architecture. Recent investigations on the chloroplast genomes of the
      tiny prasinophyceans Ostreococcus tauri (Mamiellales), Micromonas sp. RCC299
      (Mamiellales), and Pycnococcus provasolii (Pseudocourfieldiales) highlighted
      their extreme compaction and reduced gene repertoires. Genome compaction is also
      exemplified by the Ostreococcus and Micromonas mitochondrial DNAs (mtDNAs)
      although they have retained almost all of the about 65 genes presumably present
      in the mitochondria of ancestral prasinophyceans. In this study, the
      mitochondrial genome of Pycnococcus was sequenced and compared to those of
      previously examined chlorophytes. Our results document the first case where
      cellular reduction of a free-living alga was accompanied by marked reduction in
      gene content of both the mitochondrial and chloroplast genomes. At 24,321 bp, the
      intronless Pycnococcus mitochondrial genome falls within the lower size range
      displayed by green algal mtDNAs. The 36 conserved genes, specifying two rRNAs
      with conventional structures, 16 tRNAs and 18 proteins, are all encoded on the
      same DNA strand and represent 88% of the genome. Besides a pronounced codon bias,
      the protein-coding genes feature a variant genetic code characterized by the use
      of TGA (normally a stop codon) to code for tryptophan, and the unprecedented use
      of TTA and TTG (normally leucine codons) as stop codons. We conclude that
      substantial reduction of the mitochondrial genome occurred in at least three
      independent chlorophyte lineages and that this process entailed a number of
      convergent changes in these lineages.

PMID- 20135106
TI  - Development of the endocardium.
AB  - The endocardium, the endothelial lining of the heart, plays complex and critical
      roles in heart development, particularly in the formation of the cardiac valves
      and septa, the division of the truncus arteriosus into the aortic and pulmonary
      trunks, the development of Purkinje fibers that form the cardiac conduction
      system, and the formation of trabecular myocardium. Current data suggest that the
      endocardium is a regionally specialized endothelium that arises through a process
      of de novo vasculogenesis from a distinct population of mesodermal cardiogenic
      precursors in the cardiac crescent. In this article, we review recent
      developments in the understanding of the embryonic origins of the endocardium.
      Specifically, we summarize vasculogenesis and specification of endothelial cells
      from mesodermal precursors, and we review the transcriptional pathways involved
      in these processes. We discuss the lineage relationships between the endocardium
      and other endothelial populations and between the endocardium and the myocardium.
      Finally, we explore unresolved questions about the lineage relationships between
      the endocardium and the myocardium. One of the central questions involves the
      timing with which mesodermal cells, which arise in the primitive streak and
      migrate to the cardiac crescent, become committed to an endocardial fate. Two
      competing conceptual models of endocardial specification have been proposed. In
      the first, mesodermal precursor cells in the cardiac crescent are prespecified to
      become either endocardial or myocardial cells, while in the second, fate
      plasticity is retained by bipotential cardiogenic cells in the cardiac crescent.
      We propose a third model that reconciles these two views and suggest future
      experiments that might resolve this question.

PMID- 20135107
TI  - MicroRNAs in cardiac development and remodeling.
AB  - MicroRNAs (miRNAs) are a class of highly conserved, small, noncoding RNAs that
      play roles in a wide range of biologic processes. Dysregulated miRNA expression
      has been associated with human cardiovascular disease, and studies using animal
      models have shown that miRNAs are essential for cardiac development and
      remodeling. These previously unrecognized small molecules shed new light on the
      regulatory mechanisms underlying cardiac development and pathology, suggesting
      the potential importance of miRNAs as diagnostic markers and therapeutic targets
      for cardiovascular disease.

PMID- 20135108
TI  - Riley Heart Center Symposium on Cardiac Development 2009: Transcriptional
      Unification of Heart Morphogenesis.

PMID- 20135109
TI  - Infected thyroglossal duct cyst.

PMID- 20135110
TI  - Transient elastography in patients with cystic fibrosis.
AB  - BACKGROUND: Hepatic involvement is frequent in patients with cystic fibrosis
      (CF), with focal biliary cirrhosis being the pathognomonic hepatic manifestation.
      In around one-quarter of CF patients, it results in CF-associated liver disease
      (CFLD). This occurs as a relatively early complication with the majority of
      patients presenting in childhood or their early teens. However, a normal US does
      not preclude significant liver fibrosis and liver biopsy is an invasive procedure
      that is hampered by potential sampling errors. Transient elastography (TE)
      (Fibroscan) is a non-invasive, user-friendly and quick technique that provides an
      objective and reproducible measure of liver stiffness. This is accomplished with
      a device using an US probe mounted in the axis of a vibrator. Vibrations are
      transmitted by the transducer, inducing an electronic shear wave that propagates
      through the underlying tissue. OBJECTIVES: We aimed to prospectively compare TE
      and transabdominal US scanning in children and adults attending a CF clinic.
      MATERIALS AND METHODS: A total of 134 consecutive patients with documented CF
      were prospectively studied. In each case, transient elastography measurement was
      performed immediately after the routine annual US evaluation of the liver.
      Sonographic appearance of the liver was classified from 1 to 5. Ten validated TE
      measurements were performed in each patient with the result expressed in
      kilopascals (kPa). The median value was considered representative of the elastic
      modulus of the liver. RESULTS: Measurements were performed in 59 CF adults, 75 CF
      children and 31 control children. There was no relationship between age and liver
      stiffness in either the control group or CF patients. Elasticity values of
      controls, CF pancreatic sufficient (PS) patients and pancreatic insufficient (PI)
      CF patients with a US score <3 were comparable and significantly lower than in CF
      patients with a US score > or = 3 (all PI) (P < 0.002). Median elasticity in CF
      patients was significantly higher in males (4.7 kPa) than in females (3.9 kPa) (P
      = 0.0013). CONCLUSION: Considering the limitations of US and the low risk-benefit
      rate of liver biopsy in most CF patients, this preliminary study suggests that TE
      is an attractive non-invasive way to assess and follow-up liver disease in these
      patients.

PMID- 20135111
TI  - Rudhe syndrome: reversible right middle lobe emphysema in infants with left-to
      right shunts--an historical review.
AB  - In 1971, the Swedish radiologist Ulf Rudhe wrote a provocative paper on right
      middle lobe emphysema in infants with left-to-right shunts in which he suggested
      cardiac surgery rather than lung resection. At the time, this was counter to
      accepted medical practice. Earlier diagnosis and better medical management of
      ventricular septal defect in infants has proved Rudhe correct. However, two
      current cases of large left-to-right shunts in infants with emphysema of the
      right middle lobe prompt this historical review of what seemed a closed-episode
      in pediatric cardiac surgery.

PMID- 20135112
TI  - Gliomatosis peritonei of the scrotal sac associated with an immature gastric
      teratoma.
AB  - A male infant presented with bilateral scrotal masses 7 months after removal of
      an immature gastric teratoma. After surgical excision, histology showed
      gliomatosis peritonei. We report an unusual presentation of gliomatosis peritonei
      arising from a rare lesion of immature gastric teratoma.

PMID- 20135113
TI  - Chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a rare congenital immunodeficiency
      characterized by recurrent bacterial and fungal infections as well as granuloma
      formation. The manifestations of this disease can involve single or multiple
      organ systems. The lungs are the most commonly affected organ; however,
      lymphatic, hepatic, skeletal, gastrointestinal, genitourinary, head and neck, and
      central nervous system involvement have also been described. Most patients
      present with symptoms in their first few years of life. Due to the nonspecific
      manner in which patients present, the pediatric radiologist may be among the
      first to recognize the pattern of infection, inflammation, and granuloma
      formation leading to a diagnosis of CGD. The purpose of this paper is to review
      the imaging findings of CGD that can manifest throughout the body.

PMID- 20135114
TI  - Isolated congenital pseudarthrosis of the fibula.

PMID- 20135115
TI  - Isolated extramedullary relapse of acute lymphoblastic leukemia in the breast of
      an adolescent girl: radiologic findings and discussion.
AB  - We report a case of isolated extramedullary leukemia relapse in the breast of an
      adolescent girl. A 13-year-old girl with acute lymphoblastic leukemia in
      remission, post-chemotherapy and unrelated cord blood transplant, presented with
      a breast lump. US and mammography demonstrated a large hypervascular
      heterogeneous mass. Examination of tissue provided by US-guided core biopsy
      confirmed focal leukemic relapse. US is a commonly used diagnostic tool in
      children and adolescents with a breast mass, for both characterization and guided
      biopsy.

PMID- 20135116
TI  - Pediatric Burkitt lymphoma presenting as acute pancreatitis: MRI characteristics.
AB  - Acute pancreatitis is a rare initial presentation of non-Hodgkin lymphoma with
      few reported cases described in older adults and even fewer in children. MRI
      features of Burkitt lymphoma of the pancreas are sparse in the radiologic
      literature. We present a 6-year-old boy who presented with pancreatitis and
      obstructive jaundice, which was the result of Burkitt lymphoma of the pancreas.
      The imaging findings of pancreatic involvement of Burkitt lymphoma on MRI are
      discussed and the contributory role of the radiologist in guiding the appropriate
      clinical work-up of this disease is highlighted.

PMID- 20135117
TI  - Sensor combination and chemometric variable selection for online monitoring of
      Streptomyces coelicolor fed-batch cultivations.
AB  - Fed-batch cultivations of Streptomyces coelicolor, producing the antibiotic
      actinorhodin, were monitored online by multiwavelength fluorescence spectroscopy
      and off-gas analysis. Partial least squares (PLS), locally weighted regression,
      and multilinear PLS (N-PLS) models were built for prediction of biomass and
      substrate (casamino acids) concentrations, respectively. The effect of
      combination of fluorescence and gas analyzer data as well as of different
      variable selection methods was investigated. Improved prediction models were
      obtained by combination of data from the two sensors and by variable selection
      using a genetic algorithm, interval PLS, and the principal variables method,
      respectively. A stepwise variable elimination method was applied to the three-way
      fluorescence data, resulting in simpler and more accurate N-PLS models. The
      prediction models were validated using leave-one-batch-out cross-validation, and
      the best models had root mean square error of cross-validation values of 1.02 g
      l(-1) biomass and 0.8 g l(-1) total amino acids, respectively. The fluorescence
      data were also explored by parallel factor analysis. The analysis revealed four
      spectral profiles present in the fluorescence data, three of which were
      identified as pyridoxine, NAD(P)H, and flavin nucleotides, respectively.

PMID- 20135118
TI  - Peptide nucleic acids (PNAs) antisense effect to bacterial growth and their
      application potentiality in biotechnology.
AB  - Peptide nucleic acids (PNAs) are nucleic acid analogs having attractive
      properties such as quiet stability against nucleases and proteases, and they form
      strong complexes with complementary strands of DNA or RNA. Because of this
      attractive nature, PNA is often used in antisense technology to inhibit gene
      expression and microbial cell growth with high specificity. Many bacterial
      antisense or antiribosomal studies using PNA oligomers have been reported so far,
      and parameters to design effective antisense PNAs and to improve PNA cell entry
      for efficient inhibition of bacterial growth have been presented. However, there
      are still several obstacles such as low cellular uptake of PNA while applying
      antisense PNAs to a complex microbial community. On overcoming these problems,
      the PNA antisense technique might become a very attractive tool not only for
      controlling the microbial growth but also for further elucidating microbial
      ecology in complex microbial consortia. Here, we summarize and present recent
      studies on the development of antimicrobial PNAs targeting mRNAs and rRNAs. In
      addition, the application potentiality of antisense techniques in nonclinical
      biotechnology fields is discussed.

PMID- 20135119
TI  - Increasing unsaturated fatty acid contents in Escherichia coli by coexpression of
      three different genes.
AB  - Biodiesel is an interesting alternative energy source and is used as substitute
      for petroleum-based diesel. Microorganisms have been used for biodiesel
      production due to their significant environmental and economic benefits. However,
      few researches have investigated the regulation of fatty acid composition of
      these microbial diesels. Fatty acid biosynthesis in Escherichia coli has provided
      a paradigm for other bacteria and plants. By overexpressing two genes (fabA and
      fabB) associated with unsaturated fatty acid (UFA) synthesis in E. coli, we have
      engineered an efficient producer of UFAs. Saturated fatty acid (SFA) contents
      decreased from 50.2% (the control strain) to 34.6% (the recombinant strain
      overexpressing fabA and fabB simultaneously) and the ratio of cis-vaccenate
      (18:1Delta11), a major UFA in E. coli, reached 51.1% in this recombinant strain.
      When an Arabidopsis thaliana thioesterase (AtFatA) was coexpressed with these two
      genes, 0.19 mmol l(-1) fatty acids was produced by this E. coli strain after 18-h
      culture under shake-flask conditions. Free fatty acids made up about 37.5% of
      total fatty acid concentration in this final engineered strain carrying fabA,
      fabB, and AtFatA, and the ratio of UFA/SFA reached 2.3:1. This approach offers a
      means to improve the fatty acid composition of microdiesel and might pave the way
      for production of biodiesel equivalents using engineered microorganisms in the
      near future.

PMID- 20135120
TI  - Acceptance testing for nuclear medicine instrumentation.

PMID- 20135121
TI  - Immunohistological evaluation of proprioceptive potential of the residual stump
      of injured anterior cruciate ligaments (ACL).
AB  - To evaluate proprioceptive potential in residual remnants, tissue harvested from
      ruptured ACLs in 63 consecutive patients was examined for evidence of residual
      proprioceptive fibres using H&E, and monoclonal antibodies to S-100 and NFP
      (neurofilament protein). Histological examination showed good subsynovial and
      intra-fascicular vascularity with free nerve endings in the majority.
      Morphologically normal mechanoreceptors (H&E) and proprioceptive fibres
      (positivity with monoclonal antibody for NFP) were found in 46% and 52.4% of
      stumps, respectively. A statistically significant correlation between injury
      duration and persistence of mechanoreceptors and proprioceptive fibres was noted.
      More fibres were seen where ACL remnant was adherent to PCL. Our study has shown
      that persistent residual proprioceptive fibres in injured ACLs (especially early
      cases with PCL adherence) are significant; not shaving ACL remnants may be of
      potential benefit during ACL reconstruction, as some re-innervation and recovery
      of proprioceptive potential may be possible, thus improving clinical outcomes.

PMID- 20135122
TI  - Comments on Yang H-L et al.: Fluoroscopically-guided indirect posterior reduction
      and fixation of thoracolumbar burst fractures without fusion.

PMID- 20135123
TI  - Fractures of the distal humerus in elderly patients treated with a ring fixator.
AB  - The aim of distal humerus fracture treatment is articular surface reduction and
      stable fixation for early mobilisation and rehabilitation. This is usually
      performed by open reduction and internal fixation with plates. In the elderly
      osteoporotic patient this treatment is difficult to achieve due to fixation
      failure in fragile bone. We present our experience with treatment by closed
      reduction and external fixation with a non-bridging ring fixator in distal
      humerus fractures in elderly patients. There were ten females, aged 70-89
      (average 78.4). Fracture types (AO/ASIF) included three supracondylar fractures
      (type A) and seven intercondylar fractures (type C). All patients were treated by
      closed reduction and external fixation with a non-bridging ring fixator of the
      distal humerus and immediate postoperative mobilisation of the elbow. External
      fixation was removed on an average of 72 days (range 62-90). All fractures
      united. Average time to union was 56 days. Average range of movement at six
      months was 22 degrees  extension lag (range 15 degrees -30 degrees ) and 115
      degrees  flexion (range 110 degrees -120 degrees ). Complications included one
      patient with transient radial palsy and one patient with a superficial decubitus
      ulcer on the chest wall from the hardware. Minimally invasive treatment by closed
      reduction and external fixation with a ring fixator is effective for treatment of
      fractures of the distal humerus in elderly patients with osteoporotic bone. This
      treatment enables immediate mobilisation of the elbow, and allows return to
      function. It should be considered an alternative to open reduction and internal
      fixation or total elbow replacement.

PMID- 20135125
TI  - Superior vena cava stent migration into the pulmonary artery causing fatal
      pulmonary infarction.
AB  - Migration of superior vena cava (SVC) stents is a well-recognised complication of
      their deployment, and numerous strategies exist for their retrieval. To our
      knowledge, only three cases of migration of an SVC stent to the pulmonary
      vasculature have previously been reported. None of these patients developed
      complications that resulted in death. We report a case of SVC stent migration to
      the pulmonary vasculature with delayed pulmonary artery thrombosis and death from
      pulmonary infarction. We conclude that early retrieval of migrated stents should
      be performed to decrease the risk of serious complications.

PMID- 20135126
TI  - Percutaneous transosseous embolization of internal iliac artery aneurysm type II
      endoleak: report of two cases.
AB  - This report describes two cases of successful treatment of an internal iliac
      artery aneurysm (IIAA) type II endoleak utilizing a percutaneous transosseous
      access that could not be treated using an endovascular or standard percutaneous
      approach. A direct percutaneous approach through bone was chosen to avoid vital
      structures and the surrounding bowel. The procedure was successful and required
      minimal fluoroscopy time compared with other treatment options. We believe this
      procedure is an alternative to some of the more complex and technically
      challenging means of treating this lesion.

PMID- 20135127
TI  - ZAP70: a master regulator of adaptive immunity.
AB  - The protein tyrosine kinase ZAP70 became the subject of intense scrutiny in the
      early nineties, when ZAP70 mutations were characterized in several young patients
      presenting with severe T cell immunodeficiencies. The association of a lack of
      expression of ZAP70 with an immunodeficiency consisting in a markedly reduced T
      lymphocyte-mediated immunity highlighted the crucial role of this tyrosine kinase
      in T cell development and function. This discovery was soon accompanied by the
      characterization of the substrates of ZAP70 and the signalling cascades that
      depend on ZAP70 activity. These studies demonstrated that ZAP70 was indeed at the
      crossroad of several signalling pathways that control T lymphocyte development
      and function. Recently, a revival of interest for this protein came again from
      studies associating abnormal ZAP70 expression with pathological conditions. Some
      chronic lymphocytic leukemia B cells were shown to express ZAP70, and this
      expression was correlated with bad prognosis. Mouse models also revealed that
      partial defects in ZAP70 activity can be associated with autoimmunity. These last
      results suggested that ZAP70 is involved in the fine balance between immunity and
      tolerance. In this review, we will discuss the role of ZAP70 in T cell activation
      and focus on what we learnt from pathological conditions associated with
      defective expression or activity of the ZAP70 kinase.

PMID- 20135128
TI  - Species-specific behavioral patterns correlate with differences in synaptic
      connections between homologous mechanosensory neurons.
AB  - We characterized the behavioral responses of two leech species, Hirudo verbana
      and Erpobdella obscura, to mechanical skin stimulation and examined the
      interactions between the pressure mechanosensory neurons (P cells) that innervate
      the skin. To quantify behavioral responses, we stimulated both intact leeches and
      isolated body wall preparations from the two species. In response to mechanical
      stimulation, Hirudo showed local bending behavior, in which the body wall
      shortened only on the side of the stimulation. Erpobdella, in contrast,
      contracted both sides of the body in response to touch. To investigate the
      neuronal basis for this behavioral difference, we studied the interactions
      between P cells. Each midbody ganglion has four P cells; each cell innervates a
      different quadrant of the body wall. Consistent with local bending, activating
      any one P cell in Hirudo elicited polysynaptic inhibitory potentials in the other
      P cells. In contrast, the P cells in Erpobdella had excitatory polysynaptic
      connections, consistent with the segment-wide contraction observed in this
      species. In addition, activating individual P cells caused asymmetrical body wall
      contractions in Hirudo and symmetrical body wall contractions in Erpobdella.
      These results suggest that the different behavioral responses in Erpobdella and
      Hirudo are partly mediated by interactions among mechanosensory cells.

PMID- 20135129
TI  - Effects of training on lipid metabolism in swimming muscles of sea trout (Salmo
      trutta).
AB  - We examined the effect of exercise intensity and endurance training on plasma
      free fatty acid (FFA) kinetics and lipid metabolism in swimming muscles of reared
      sea trout. In both training groups [water current velocities 1 and 2 body lengths
      per second (bl s(-1))] the plasma level of FFAs decreased significantly (P <
      0.001) compared to the control group. Similar significant (P < 0.01) post
      exercise decrease was observed also in the lipase-esterase activity in the red
      muscle, but not in white. Moreover, in the group swimming with higher intensity a
      significantly higher (P < 0.05) lipase-esterase activity in the red muscle was
      found compared with the group on moderate exercise. As with cytochrome c oxidase
      activity, a significant elevation in the enzyme activity was also observed after
      training in the 1 bl s(-1) group in red and white muscle (P < 0.05 and P < 0.01,
      respectively). No changes were observed in beta hydroxyacyl CoA dehydrogenase
      activity. The lipid content was on average nine times higher in red compared to
      white muscle being 16.7, 21.1, and 24.9% in the red muscle of the control, 1 and
      2 bl s(-1) groups, respectively, with a significant (P < 0.05) increase after
      training. We conclude that (1) unlike in mammals, plasma FFA kinetics and
      oxidation are not linearly related to exercise intensity in reared sea trout, (2)
      training enhances the capacity to uptake FFA from plasma, and (3) high intensity
      training shifts the proportion of energy derived from fat oxidation to
      carbohydrate-derived energy.

PMID- 20135130
TI  - The corrected QT interval in 24 h ECGs in neonates.
AB  - BACKGROUND: A prolongation of the corrected QT interval (QTc) in the routine ECG
      of otherwise healthy neonates has been suspected to be a risk factor for sudden
      infant death. None of the studies published so far differentiated between awake
      and sleeping neonates. OBJECTIVE: This study was designed to find possible
      differences of the QTc when neonates were asleep or awake, and to provide guide
      values for neonatal QTc in 24-h ECGs. METHODS: Hundred neonates (51 male, 49
      female, age 2-11 days) underwent ambulatory ECG with defined lead positions. The
      QT interval was measured constantly in three different leads, and the corrected
      QT interval was calculated using Bazett's formula. We compared the QTc obtained
      during sleep with the QTc obtained from wake periods. RESULTS: The heart rate was
      significantly higher when the neonates were awake, and when awake higher in girls
      than in boys. While there was no statistically significant difference between the
      QTc when the babies were awake or asleep in leads 1 and 3, this reached the level
      of mathematical significance in the most cranio-caudal lead 2. CONCLUSION:
      Changes of the corrected QT interval in neonates seems to be dependent on the
      lead position of ambulatory ECGs, and could be found only in one lead. Guide
      values for the sleeping and awake neonate are provided.

PMID- 20135131
TI  - Low intrinsic aerobic exercise capacity and systemic insulin resistance are not
      associated with changes in myocardial substrate oxidation or insulin sensitivity.
AB  - In patients, inactivity, obesity and insulin resistance are associated with
      increased incidence of heart failure. Rats selectively bred for low (LCR)
      intrinsic aerobic exercise capacity show signs of the metabolic syndrome
      including insulin resistance, compared to their counterparts bred for high
      intrinsic aerobic capacity (HCR). We reasoned that systemic insulin resistance in
      LCR should translate to impaired substrate oxidation and reduced insulin
      sensitivity in the heart. Isolated hearts were perfused in the working mode to
      analyze cardiac function, substrate oxidation patterns, insulin response, and
      oxygen consumption. After 22 generations of selective breeding, LCR displayed
      reduction of exercise capacity (LCR vs. HCR: distance 280 +/- 12 vs. 1,968 +/- 63
      m, time 19.5 +/- 0.6 vs. 71.7 +/- 1.4 min, speed 19.2 +/- 0.3 vs. 45.3 +/- 0.7
      m/min; all p < 0.05). At 21 weeks, body weight (+34%), tibia length (+6%), heart
      weight (+31%), and heart weight to tibia length ratio (+24%; all p < 0.05) were
      increased. LCR display higher random glucose, higher fasting glucose, and higher
      insulin levels in serum than HCR indicating the presence of insulin resistance in
      LCR. Here, in contrast, isolated hearts showed no differences in glucose (0.22 +/
      0.02 micromol/min/g dry) or fatty acid oxidation (0.79 +/- 0.10 micromol/min/g
      dry), oxygen consumption (28.3 +/- 4.1 nmol O(2)/min/g dry) or cardiac power
      (18.6 +/- 1.6 mW/g dry). Furthermore, sensitivity to insulin (Deltaglucose
      oxidation: +0.57 +/- 0.095 mumol/min/g dry) was not different between the two
      populations. Low intrinsic exercise capacity and systemic insulin resistance in
      rats are not associated with changes in cardiac substrate oxidation, insulin
      sensitivity, oxygen consumption, or cardiac function. The lack of cardiac insulin
      resistance in the face of systemic insulin resistance supports a concept of
      different pathomechanisms for these two conditions.

PMID- 20135132
TI  - The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets
      in the treatment of atrophic vaginitis: a randomized controlled trial.
AB  - OBJECTIVE: To compare the effectiveness of the vaginal tablets of hyaluronic acid
      and estrodiol for the treatment of atrophic vaginitis. MATERIALS AND METHODS:
      Forty-two postmenopausal women with symptoms of atrophic vaginitis were
      randomized to take vaginal tablets of 25 MUg estradiol (n = 21) (group I) or 5 mg
      hyaluronic acid sodium salt (n = 21) (group II) for 8 weeks. The symptoms of
      atrophic vaginitis were evaluated by a self-assessed 4-point scale of composite
      score and the degree of epithelial atrophy was determined as, none, mild,
      moderate and severe. Vaginal pH and maturation index were measured and compared
      in both the groups. RESULTS: The symptoms were relieved significantly in both the
      groups (P < 0.001). The relief of symptoms was significantly superior in group I
      compared with group II (P < 0.05). A significant decrease in epithelial atrophy
      and vaginal pH were detected in both the groups (P < 0.01) after treatment. The
      vaginal maturation values were also significantly improved at both study groups
      (P < 0.001). The mean maturation value was significantly higher in group I when
      compared with group II (P < 0.001). CONCLUSION: Both treatments provided relief
      of vaginal symptoms, improved epithelial atrophy, decreased vaginal pH, and
      increased maturation of the vaginal epithelium. Those improvements were greater
      in group I. Hyaluronic acid vaginal tablets can be used in patients with atrophic
      vaginitis who do not want to or can not take local estrogen treatment.

PMID- 20135133
TI  - Paraneoplastic consumptive coagulopathy related to intramyometrial low-grade
      endometrial stromal sarcoma coexistent with adenomyosis diagnosed 7 years after
      laparoscopic-assisted myomectomy.
AB  - INTRODUCTION: Paraneoplastic coagulation disorders associated with benign and
      malignant gynecological tumors have been reported. However, reports on cutaneous
      purpural manifestation of paraneoplastic coagulopathy in cases of gynecological
      tumors are extremely limited. CASE REPORT: A 40-year-old woman was referred due
      to generalized ecchymosis 7 years after laparoscopic-assisted myomectomy.
      Coagulogram was markedly deranged with severe thrombocytopenia. After
      hematological disorders were excluded, image diagnostic modalities showed
      multiple intramyometrial heterogeneous mass lesions with extensive intratumoral
      hemorrhage. Laparoscopic-assisted vaginal hysterectomy was performed with
      supplementation of coagulation factors and platelets. Histological examination
      showed intramyometrial low-grade endometrial stromal sarcoma (ESS) coexistent
      with adenomyosis. Coagulation disorder immediately disappeared after hysterectomy
      and the postoperative course was uneventful. Recurrence of either ESS or
      coagulopathy has not been noted 15 months postoperatively, to date. CONCLUSIONS:
      This case illustrates a rare but potentially life-threatening consumptive
      coagulopathy caused by intramyometrial low-grade ESS that was assumed to
      secondarily arise from stromal cells of adenomyosis developed in postmyomectomy
      scar.

PMID- 20135134
TI  - Reference range of fetal splenic circumference from 14 to 40 weeks of gestation.
AB  - OBJECTIVE: To create a nomogram for fetal splenic circumference of normal
      fetuses. MATERIALS AND METHODS: A prospective, cross-sectional study was
      undertaken on normal pregnancies with certain date from 14 to 40 weeks of
      gestation. All fetuses were measured for fetal splenic circumference by tracing
      technique on transverse view of the fetal abdomen, using high-resolution real
      time ultrasound with a 2-4 MHz convex transducer. RESULTS: A total of 684 normal
      pregnant women between 14 and 40 weeks of gestation were recruited. Fifty-eight
      were excluded because of poor image quality and fetal abnormality. The remaining
      626 were available for analysis. Quadratic equation model was best fitted to
      estimate the 5th, 50th and 95th percentile range of splenic circumference at each
      gestational week. Fetal splenic circumference was gradually increased with
      gestational age with fitted equation as follows: splenic circumference (cm) = 
      4.181 + 0.456 (GA) -0.001 (GA)(2) (r = 0.942, p < 0.001). The table of nomogram
      for various percentile ranges was constructed. CONCLUSION: A normal reference
      range of fetal splenic circumference for each week of gestational age during 14
      40 weeks is established.

PMID- 20135135
TI  - Clinicopathological and immunohistochemical analysis of sclerosing stromal
      tumours of the ovary.
AB  - INTRODUCTION: Sclerosing stromal tumours (SST) of the ovary are rare, benign
      tumours. SSTs are usually hormone inactive and tend to occur in the second and
      third decades of life. The most common clinical symptom is menstrual
      irregularity. MATERIALS AND METHODS: Fourteen women diagnosed with SST of the
      ovary were included in this study. Tumour samples were collected, embedded in
      paraffin and stained with haematoxylin and eosin, periodic acid-Schiff (PAS), and
      PAS with digestion, as well as immunohistochemically for vimentin, smooth muscle
      actin, desmin, CD 99, inhibin-alpha and the oestrogen and progesterone receptor.
      RESULTS: The age of the patients ranged from 16 to 54 years (mean age 25.2
      years). The tumours ranged in size from 6 to 21 cm (mean 10.5 cm).
      Macroscopically, eight tumours were solid and six were solid and cystic. All SSTs
      were well circumscribed with pseudolobule formation. Spindle-shaped fibroblast
      like cells and vacuolated theca-like cells were prominent. Blood vessels
      exhibited a hemangiopericytomatous pattern and boomerang-like features.
      Immunohistochemical results were as follows: vimentin, 14/14 cases positive;
      smooth muscle actin, 14/14 cases positive; desmin, 14/14 cases positive; CD 99,
      4/14 cases positive; inhibin-alpha, 14/14 cases positive; oestrogen receptor,
      0/14 cases positive; progesterone receptor, 2/14 cases positive. CONCLUSIONS: The
      characteristic histopathological features we observed in our study are usually
      adequate for the diagnosis of SSTs. Although inhibin-alpha, CD 99 and desmin
      staining may be a useful and reliable tool for SST diagnosis in problematic
      cases, an immunohistochemical panel will not discriminate from other tumours in
      the sex cord-stromal group.

PMID- 20135136
TI  - Urinary calcium and magnesium excretion relates to increase in blood pressure
      during pregnancy.
AB  - OBJECTIVE: Pregnancy-induced hypertension and preeclampsia are serious clinical
      manifestations during late pregnancy and the cause for increased maternal and
      foetal morbidity and mortality. The pathogenesis is unknown but experience from
      treatment schemes suggests that minerals may be of importance. Mineral
      homeostasis is influenced by acid-base conditions. The aim of the study was to
      elucidate the relation between acid-base balance, urinary mineral excretion and
      blood pressure during pregnancy. DESIGN: A prospective observational study of a
      general population. MATERIALS AND METHODS: The study was performed at the Midwife
      Health Center in Boras, Sweden, where practically all pregnant subjects in the
      catchment area are registered. First time pregnant subjects (n = 123) were
      voluntarily recruited without exclusion criteria. A 24 h urine sample was
      collected at pregnancy week 12 and analyzed for creatinine, calcium, magnesium,
      and urea as a proxy for acid conditions. Blood pressure was recorded every 2-3
      weeks until delivery. RESULTS: There was a relation between the excretion of urea
      and calcium and magnesium at week 12. A blood pressure increase was found after
      pregnancy week 30 but only among subjects who had a high excretion of calcium and
      magnesium at week 12. CONCLUSIONS: If an increase in blood pressure during the
      later part of pregnancy a risk indicator for preeclampsia, the results suggest
      that an excessive secretion of calcium leading to a functional deficit might be a
      risk indicator for gestational hypertension and preeclampsia. Intervention
      experiments are required to assess this hypothesis.

PMID- 20135137
TI  - Sexual experience and risky sexual behaviours of Turkish university students.
AB  - OBJECTIVES: To determine the sexual experience and risky sexual behaviours of
      Turkish university students. MATERIALS AND METHODS: This cross-sectional
      questionnaire survey was carried out in a state university in central Turkey. The
      data were collected in the 2006-2007 academic year in this university.
      Participants were 949 convenience students from this university. The study group
      was determined by a stratified sampling method, with faculty and sex representing
      the strata. Data were collected with the questionnaire designed by researchers to
      determine the personal features, sexual experience and risky sexual behaviours of
      students. A chi-square test was applied in the statistical analysis of data.
      RESULTS: Of all the students in the research; 42.9% were female and 57.1% male.
      The percentage of students having had sexual experience was 33.8%. Of the
      students having had sexual experience, 17.1% were sexually active. The average
      age for first sexual experience was 17.47 +/- 1.79. Among sexually active
      students, 51.9% indicated that they had unprotected sexual intercourse, 64.2% had
      sexual intercourse when they were intoxicated and 59.3% had more than one sexual
      partner. CONCLUSIONS: According to the results obtained from this research, it
      can be said that a considerable number of the university students had sexual
      experience and those who are sexually active are under the risk of important
      health problems, such as sexually transmitted diseases and unintended pregnancy.

PMID- 20135138
TI  - The effect of physical effort on retinal activity in the human eye: rod and cone
      flicker electroretinogram studies.
AB  - BACKGROUND: The aim of our study was to assess the effect of physical exercise
      with increasing intensity on neuroretinal activity in healthy subjects (n = 30).
      METHOD: We analysed the amplitude and implicit time of b-wave electroretinogram
      (ERG) responses in two experiments: (1) for a scotopic blue 10 Hz flicker
      stimulus (rod-mediated responses), and (2) for a photopic white 30 Hz flicker
      stimulus (cone-mediated responses). Using a cycloergometer, three 10-minute
      effort-tests with increasing intensity were performed. Each participant was
      assigned individual workload values (W) below the lactate threshold (40%
      VO(2)max), at the lactate threshold (60-65% VO(2)max) and above the lactate
      threshold (80% VO(2)max). Five ERG recordings were taken: (1) before, (2-4)
      immediately after the three subsequent efforts and (5) 1 hour after the
      completion of the last effort. The right eye was selected for monocular
      stimulation in both experiments. RESULTS: After the first effort (40% VO(2)max),
      we observed an increased amplitude (p < 0.001) and decreased implicit time of the
      b-wave (p < 0.01) in cone-mediated responses, and no significant effects in rod
      mediated responses. Despite the increase in effort intensity, the cone b-wave
      amplitude remained unchanged, whereas the rod b-wave amplitude significantly
      decreased after the subsequent efforts (p < 0.001). CONCLUSIONS: Rod-mediated
      responses were more susceptible to effort-induced homeostasis disruptions than
      the cone-mediated responses. The application of ERGs may be used as
      neurophysiological criteria in defining the cardiovascular status of the physical
      performance.

PMID- 20135139
TI  - Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic
      retinopathy.
AB  - BACKGROUND: The purpose of this study is to evaluate the role, the safety and the
      effectiveness of intravitreal bevacizumab (IVB) injections as an adjunct to
      vitrectomy in the management of severe proliferative diabetic retinopathy (PDR).
      DESIGN: Case-Control Study METHODS: Randomized controlled trial performed on 72
      eyes of 68 patients affected by vitreous haemorrhage (VH) and tractional retinal
      detachment (TRD), which occurred as a consequence of active proliferative
      diabetic retinopathy (PDR). We randomly assigned eligible patients in a 1: 1: 1
      ratio to receive a sham injection or an intravitreal injection of 1.25 mg of
      bevacizumab, either 7 or 20 days before the vitrectomy. In order to obtain three
      homogeneous groups of surgical complexity, we assigned to the following
      preoperative parameters a score from 0 to 3: a) vitreous haemorrhage, b) prior
      retinal laser-photocoagulation, c) morphological types of retinal detachment such
      as focal, hammock, central diffuse, table-top. Complete ophthalmic examinations
      and color fundus photography were performed at baseline and 1, 6, 12, and 24
      weeks after the surgery. MAIN OUTCOME MEASURES: Intraoperative management,
      safety, efficacy of IVB at different time injection as an adjunct to vitrectomy
      in the management of severe PDR RESULTS: Group A (sham injection): intraoperative
      bleeding occurred in 19 cases (79.1%), the use of endodiathermy was necessary in
      13 patients (54.1%), relaxing retinotomy was performed on one patient (4.1%), and
      in four cases (16.6%) iatrogenic retinal breaks occurred. The surgical mean time
      was 84 minutes (SD 12 minutes). Group B (bevacizumab administered 7 days before
      vitrectomy): intraoperative bleeding occurred in two cases (8.3%) and the use of
      endodiathermy was necessary in two patients (8.3%). No iatrogenic breaks occurred
      during the surgery. The surgical mean time was 65 minutes (SD 18 minutes). Group
      C (bevacizumab administered 20 days before vitrectomy): intraoperative bleeding
      occurred in three cases (12.5%), the use of endodiathermy was necessary in three
      patients (1.5%), and an iatrogenic break occurred in one patient (4.1%) while the
      delamination of fibrovascular tissue was being performed. The surgical mean time
      was 69 minutes (SD 21 minutes). The average difference in the surgical time was
      statistically significant between group A and group B (p = 0.025), and between
      group A and group C (p = 0.031). At the end of the surgery, the retina was
      completely attached in all eyes. At the 6-month follow-up, we observed the
      development of tractional retinal detachment (TRD) in one out of 24 patients from
      group C (4%). CONCLUSIONS: A preoperative intravitreal injection of bevacizumab
      may represent a new strategy for the surgical treatment of severe PDR by reducing
      retinal and iris neovascularization: this would make surgery much easier and
      safer, thus improving the anatomical and functional prognosis. According to our
      study, the best surgical results are achieved performing the IVB 7 days
      preoperatively.

PMID- 20135140
TI  - Reduced concentrations of angiogenesis-related factors in vitreous after
      vitrectomy in patients with proliferative diabetic retinopathy.
AB  - BACKGROUND: The purpose of this study was to determine whether vitrectomy alters
      the angiogenic profile in the vitreous of eyes with proliferative diabetic
      retinopathy (PDR). METHODS: We measured the levels of angiopoietin-2, HGF, bFGF,
      PDGF, TIMP-1, and TIMP-2 by sandwich enzyme linked immunosorbent assay (ELISA) in
      vitreous samples from 27 eyes of 26 patients with PDR before pars plana
      vitrectomy (without IOL implantation) and in 12 fluid samples from 12 patients
      with PDR obtained during an IOL implantation 3.5 to 9 (mean 4.9) months after an
      earlier vitrectomy. The levels of these factors were also measured in 12 vitreous
      samples obtained from 12 eyes that had undergone epiretinal membrane (ERM) or
      macular hole (MH) surgeries. RESULTS: The mean vitreous levels of both
      angiopietin-2 (103 pg/ml) and HGF (1091 pg/ml) in the sample from eyes with PDR
      collected at the time of the IOL implantation were significantly lower than in
      those collected before the vitrectomy (P < 0.01). On the other hand, the changes
      in the levels of TIMP-1 and TIMP-2 were both not significant after vitrectomy.
      CONCLUSION: The significant decrease of angiopietin-2 and HGF in the vitreous
      fluid after vitrectomy suggests that vitrectomy shifts the eye towards an anti
      angiogenic environment.

PMID- 20135141
TI  - The correlation between the regulation of recombinant human IGF-2 on eye growth
      and form-deprivation in guinea pig.
AB  - OBJECTIVE: By investigating the effects of recombinant human IGF-2 (rhIGF-2) on
      the diopter, axial eye length and the expression of IGF-2 in non-form-deprivation
      (FD) and FD eyes of guinea pig, we tried to elucidate the relationship between
      the effects of rhIGF-2 on eye growth and FD in guinea pig. METHODS: Eighty 3-week
      old guinea pigs were included in the study, which were divided into two groups
      randomly. Group A (n = 40) was the non-FD group, Thirty-two guinea pigs received
      intravitreal injections of either 1 ng, 10 ng, 100 ng rhIGF-2 or bovine serum
      albumin (BSA) to the right eye; eight guinea pigs who received no intravitreal
      injections served as control. Group B (n = 40) was the FD group; the right eyes
      were form-deprived, and received the same disposals as group A. The diopter and
      the axial eye length of all guinea pigs were measured at day 14. The expression
      of IGF-2 in the retina was measured by Western blot. RESULTS: After 14 days, FD
      eyes were high myopia. The axial length of FD eyes was significant for longer
      than that of non-FD eyes. The expression of IGF-2 in the retina of FD eyes was up
      regulated. In non-FD group, there was no significant difference in the diopter
      and axial eye length among rhIGF-2 injection eyes, BSA injection eyes and control
      eyes, but the expression of IGF-2 in the retina of 10 ng and 100 ng rhIGF-2
      injection eyes was obviously down-regulated. In the FDM (form-deprivation myopia)
      group, the myopic diopter and axial eye length increased in 10 ng and 100 ng
      rhIGF-2 injection eyes compared with those in BSA injection eyes and control
      eyes. The level of IGF-2 expression in the retina of 10 ng and 100 ng rhIGF-2
      injection eyes was obviously down-regulated. The diopter and expression of IGF-2
      in the retina of rhIGF-2 injection eyes was negatively correlated with the dose
      of each injection, which was positively correlated with the axial length.
      CONCLUSION: RhIGF-2 intravitreous injection does not affect the diopter and axial
      length in non-FD eyes of guinea pig, while it can induce a significant increase
      in myopic diopter and axial length of FD eyes. RhIGF-2 can promote the
      development of FDM on the condition of FD.

PMID- 20135142
TI  - Enhancement of the finger cold-induced vasodilation response with exercise
      training.
AB  - Cold-induced vasodilatation (CIVD) is a cyclical increase in finger temperature
      that has been suggested to provide cryoprotective function during cold exposures.
      Physical fitness has been suggested as a potential factor that could affect CIVD
      response, possibly via central (increased cardiac output, decreased sympathetic
      nerve activity) and/or peripheral (increased microcirculation) cardiovascular and
      neural adaptations to exercise training. Therefore, the purpose of this study was
      to investigate the effect of endurance exercise training on the CIVD response.
      Eighteen healthy males trained 1 h d(-1) on a cycle ergometer at 50% of peak
      power output, 5 days week(-1) for 4-weeks. Pre, Mid, Post, and 10 days after the
      cessation of training and on separate days, subjects performed an incremental
      exercise test to exhaustion (.VO(2peak)) and a 30-min hand immersion in 8 degrees
      C water to examine their CIVD response. The exercise-training regimen
      significantly increased .VO(2peak) (Pre: 46.0 +/- 5.9, Mid: 52.5 +/- 5.7, Post:
      52.1 +/- 6.2, After: 52.6 +/- 7.6 ml kg(-1) min(-1); P < 0.001). There was a
      significant increase in average finger skin temperature (Pre: 11.9 +/- 2.4,
      After: 13.5 +/- 2.5 degrees C; P < 0.05), the number of waves (Pre: 1.1 +/- 1.0,
      After: 1.7 +/- 1.1; P < 0.001) and the thermal sensation (Pre: 1.7 +/- 0.9,
      After: 2.5 +/- 1.4; P < 0.001), after training. In conclusion, the aforementioned
      endurance exercise training significantly improved the finger CIVD response
      during cold-water hand immersion.

PMID- 20135143
TI  - Are 200 students really affecting heart rate variability and alpha-amylase
      activity?

PMID- 20135144
TI  - Evaluation of artificial sweat in athletes with spinal cord injuries.
AB  - Athletes with spinal cord injury often experience high heat storage due to
      reduced sweating capacity below the spinal injury. Spray bottle (SB) may be used
      to apply mist for evaporative cooling during breaks in competitions. This study
      examined the efficacy of SB during rest breaks. Seven participants, four female
      and three males, (mean +/- SD age 24 +/- 4.1 year, weight 56.2 +/- 7.0 kg, upper
      body VO(2) peak 2.4 +/- 0.6 l/min) volunteered for the study. Participants were
      paraplegic athletes (T3-T12/L1) with both complete and incomplete lesions.
      Participants arm-cranked using a ramp protocol in an environment of 21 +/- 1.5
      degrees C and 55 +/- 3% rh once using a SB during 1-min rest between 7-min stages
      of increasing intensity and once without the SB (CON). Mean total work was
      similar (p = 0.86) for the SB and CON (2495.7 +/- 914.6 vs. 2407.1 +/- 982.3 kJ,
      respectively). Likewise, the mean work times were similar between trials (27 +/-
      6 and 26 +/- 7 min for SB and CON, respectively). Furthermore, there were no
      significant differences detected between trials for skin temperature, rectal
      temperature, esophageal temperature (p > 0.05). There were no statistically
      significant differences detected between trials for RPE (p > 0.05). In
      conclusion, the application of artificial sweat via SB was ineffective in
      attenuating the onset of uncompensable heat strain during high-intensity arm
      exercise in a comfortable environment.

PMID- 20135145
TI  - Effects of wind and rain on thermal responses of humans in a mildly cold
      environment.
AB  - The purpose of the present study was to clarify the effects of wind and rain on
      peripheral heat loss by non-exercising minimally clothed humans in a mildly cold
      environment. Seven healthy young male subjects wearing only shorts rested in a
      standing position for 20 min at an ambient temperature of 15 degrees C under
      three conditions: without exposure to wind or rain (CON), with exposure to wind
      (3 m/s) (WIND) and with exposure to wind (3 m/s) and rain (40 mm/h) (WIND +
      RAIN). Mean heat loss measured using a heat flux transducer was significantly
      greater in the subjects exposed to WIND + RAIN compared to those exposed to CON
      and WIND conditions (p < 0.01). Metabolic heat production was significantly
      greater under WIND + RAIN than under CON and WIND (p < 0.01). Decrease in heat
      storage was significantly larger at WIND + RAIN compared with CON and WIND (p <
      0.01). Mean skin temperature was significantly lower under WIND + RAIN than under
      CON and WIND conditions (p < 0.01). These results indicate that peripheral heat
      loss significantly increases when humans are exposed to wind and rain for a short
      period (20 min) under a mildly cold condition.

PMID- 20135146
TI  - Clinical practice: Breastfeeding and the prevention of allergy.
AB  - The increase in allergic disease prevalence has led to heightened interest in the
      factors determining allergy risk, fueled by the hope that by influencing these
      factors one could reduce the prevalence of allergic conditions. The most
      important modifiable risk factors for allergy are maternal smoking behaviour and
      the type of feeding. A smoke-free environment for the child (to be), exclusive
      breastfeeding for 4-6 months and the postponement of supplementary feeding
      (solids) until 4 months of age are the main measures considered effective. There
      is no place for restricted diets during pregnancy or lactation. Although meta
      analyses suggest that hypoallergenic formula after weaning from breastfeeding
      grants protection against the development of allergic disease, the evidence is
      limited and weak. Moreover, all current feeding measures aiming at allergy
      prevention fail to show effects on allergic manifestations later in life, such as
      asthma. In conclusion, the allergy preventive effect of dietary interventions in
      infancy is limited. Counselling of future parents on allergy prevention should
      pay attention to these limitations.

PMID- 20135147
TI  - Molecular biological comparison of different Besnoitia species and stages from
      different countries.
AB  - Besnoitia besnoiti tissue cysts from a recent outbreak in cattle in Germany were
      characterized with respect to their internal transcribed spacer regions 1, 2, and
      18S rDNA gene sequences. These results were compared with own sequences of an
      Israelian isolate of B. besnoiti and of Besnoitia jellisoni cystozoites stored
      for years in liquid nitrogen. Furthermore, material was studied that was obtained
      from white mice (Balb/C) that had been successfully infected by intraperitoneal
      infection of fresh cystozoites from the German outbreak. All results were then
      compared and discussed with respect to databank sequences of other Besnoitia
      species. Comprehensive phylogenetic studies of B. besnoiti isolates from Germany
      revealed almost identical sequence alignments when compared to previously
      sequenced B. besnoiti isolates from Israel and Spain. More importantly,
      phylogenetic analysis revealed two distant clusters of Besnoitia species: the
      first one includes Besnoitia akodoni, Besnoitia darlingi, and Besnoitia
      oryctofelisi, while the second cluster includes B. besnoiti, Besnoitia bennetti,
      Besnoitia tarandi, and the Besnoitia species of rodents (B. jellisoni). The also
      B. jellisoni named species of the GenBank (AF 076860) must be another one, since
      our strain derives directly from Frenkel. These findings give strong hints that
      B. besnoiti has a cycle between rodents and a predator and that cattle and other
      are only accidental hosts.

PMID- 20135148
TI  - Serum enzyme and hematological profile of Fasciola gigantica immunized and
      experimentally infected riverine buffaloes.
AB  - Sixteen male, yearling Murrah buffaloes were randomly assigned to four groups of
      four buffaloes each. Each animal in Gr-I and II were immunized, respectively,
      with 4.8 mg of excretory secretory antigen and 1,300 microg Infection Specific
      Antigen, in three divided doses. Subsequently, each animal in Gr-I, II, and III
      was per os infected with 800 viable Fasciola gigantica metacercariae (bubaline
      origin) on week-6 after the start of the experiment, while animals in Gr-IV
      served as healthy controls. The aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) concentrations progressively increased during the
      prepatency and respectively attained the highest levels during week-6 and 8 post
      infection (PI). The alkaline phosphatase (AP) exhibited elevated trends from
      eighth week PI onward and continued to be higher until the end (p < 0.05-0.01).
      With the cessation of traumatic activities of the diastomes, the AST and ALT
      levels declined yet were throughout significantly higher than the healthy
      controls (p < 0.05-0.01). In the immunized animals (Gr-I and II), the fluctuation
      patterns were similar but the values were significantly lower than the non
      immunized (Gr-III) animals (p < 0.05-0.01). The elevated levels of the enzymes
      had positive correlation with depressed erythrocytic indices, leucocytosis,
      eosinophilia, necropsy worm recovery, and hepatic lesion score in the respective
      groups. The increased concentrations of the enzymes revealed two clearly
      demarcated stages: (a) remarkably elevated AST (40.8%) and ALT (140.0%) levels
      during the prepatency, signifying traumatic lesions inflicted by the F. gigantica
      adolescercariae and (b) the significant increase in AP (107.9%), suggestive of
      bile duct hyperplasia, cholangitis, periportal fibrosis, and biliary obstruction
      etc. from sixth week PI onward. None of healthy controls developed clinical signs
      and had normal hematological and serum enzyme profiles. Diagnostic significance
      of these marker enzymes in the disease forecasting and in time application of
      control strategies to combat tropical fasciolosis in buffaloes in the endemic
      areas has been discussed.

PMID- 20135149
TI  - Novel human pathological mutations. Gene symbol: SCN1A. Disease: Myoclonic
      epilepsy of infancy.

PMID- 20135150
TI  - Are there sex differences in the work ability of cancer survivors? Norwegian
      experiences from the NOCWO study.
AB  - BACKGROUND: This study investigated gender differences concerning work ability in
      working cancer survivors (CSs) and compared them to those of matched population
      based controls. METHODS: A mailed questionnaire was completed by 446 Norwegian
      CSs (226 breast cancer, 166 testicular and 54 prostate cancer) with good
      prognosis 2-6 years after primary treatment and 588 controls (319 females and 269
      males). Overall current work ability (OCWA) was the primary outcome measure, and
      ten indices of the physical, mental and social skill aspects of work ability (WA)
      were also studied. RESULTS: The mean OCWA score was higher amongst male CSs
      compared to females (p = 0.04). The mean OCWA score was similar in male CSs and
      controls (p  = 0.17), whilst female CSs had significantly lower mean OCWA score
      than controls (p <  0.001). Mental WA neuroticism was higher amongst women in
      both CSs (p = 0.009) and controls (p  =  0.001), and the same pattern was found
      for physical WA concerning the symptom score (p  =  0.003 and <0.001,
      respectively). Sex had no significant association with OCWA in multivariate
      analyses. Significant associations were observed for physical and mental WA, but
      not for social skills. CONCLUSIONS: OCWA was significantly better in male CSs
      than in female CSs. Male CSs did not differ from their controls, whilst female
      CSs scored significantly poorer than their controls. CSs with reduced overall
      work ability should be identified, and their mental and physical work ability
      should be examined independent of sex.

PMID- 20135151
TI  - Psychological distress and needs of cancer patients: a prospective comparison
      between the diagnostic and the therapeutic phase.
AB  - BACKGROUND AND PURPOSE: The diagnosis of cancer marks an immediate passage from a
      condition of health to one characterized by uncertainty, threat of death, and
      changes. The psychological distress is recognized as a peculiar component in the
      process of disease adjustment and it seems to change over time together with
      needs. In the present study, both psychological distress and needs were assessed
      twice (i.e., after the diagnosis and later during treatments) in a sample of
      hospitalized cancer patients. METHOD: Eighty-five consecutive adult patients from
      the same Cancer Institute in North-east Italy were involved in the research.
      Participants were requested to fill out both a distress (i.e., the Hospital
      Anxiety and Depression Scale) and needs (i.e., Needs Evaluation Questionnaire)
      self-reported measure within a month of diagnosis (diagnostic phase) and 3-6
      months from diagnosis (therapeutic phase). RESULTS: In the diagnostic phase, the
      prevalence of probable psychological morbidity due to anxiety was 23.5% and 14.1%
      due to depression. When the inpatients identified as possible cases were
      included, the respective proportions were 56.5% and 36.5%. Progressing from
      diagnostic to therapeutic phase, anxiety seems to decrease, while no
      statistically significant difference has been found in depression levels. In both
      phases, the most frequently mentioned needs were the informative ones; although
      the decrement in time is significant only for this type of needs. CONCLUSION: The
      implications both for the quality of care and the disease adjustment by cancer
      patients are discussed together with study limitations.

PMID- 20135152
TI  - Light-induced cleavage of model phenylalanine conjugates based on coumarins and
      quinolones.
AB  - In order to evaluate the application of quinolone as a new photocleavable
      protecting group, in comparison with coumarin, a series of model phenylalanine
      conjugates were prepared by reaction with chloromethylated O and N heterocycles.
      The photophysical properties of the resulting ester conjugates were evaluated as
      well as the photosensitivity under irradiation at 250, 300, 350, and 419 nm. The
      results obtained showed that the quinolone conjugates were readily photolysed,
      with complete release of the amino acid in short irradiation times and could be
      considered a new addition to the family of photocleavable protecting groups for
      the carboxylic acid function of amino acids.

PMID- 20135153
TI  - Latest news about the sulfurtransferase protein family of higher plants.
AB  - Sulfurtransferases/rhodaneses (Str) comprise a group of enzymes widely
      distributed in all phyla which catalyze in vitro the transfer of a sulfur atom
      from suitable sulfur donors to nucleophilic sulfur acceptors. The best
      characterized Str is bovine rhodanese (EC 2.8.1.1) which catalyses in vitro the
      transfer of a sulfane sulfur atom from thiosulfate to cyanide, leading to the
      formation of sulfite and thiocyanate. Plants as well as other organisms contain
      many proteins carrying a typical rhodanese pattern or domain forming multi
      protein families (MPF). Despite the presence of Str activities in many living
      organisms, the physiological role of the members of this MPF has not been
      established unambiguously. While in mammals these proteins are involved in the
      elimination of toxic cyanogenic compounds, their ubiquity suggests additional
      physiological functions. In plants, Str are localized in the cytoplasm,
      mitochondria, plastids, and nucleus. Str probably also transfer reduced sulfur
      onto substrates as large as peptides or proteins. Several studies in different
      organisms demonstrate a protein-protein interaction with members of the
      thioredoxin MPF indicating a role of Str in maintenance of the cellular redox
      homeostasis. The increased expression of several members of the Str MPF in
      various stress conditions could be a response to oxidative stress. In summary,
      data indicate that Str are involved in various essential metabolic reactions.

PMID- 20135154
TI  - Survival tactics of Ranunculus species in river floodplains.
AB  - The flooding resistance of four Ranunculus species was studied under controlled
      conditions and related to the tactics used by these species to survive in their
      natural habitat in river floodplains. R. bulbosus, a species from seldom-flooded
      river levees, was relatively intolerant of both waterlogging and complete
      submergence, due to a constitutively low level of aerenchyma in the root system.
      This lack of gas spaces resulted in high mortality rates during flooding
      treatments and an inability to use photosynthetically derived oxygen for root
      respiration during complete submergence. The pioneer R. sceleratus, predominantly
      abundant in low lying mudflats, was very resistant to waterlogging and shallow
      floods. Due to its constitutively high root porosity and its ability to greatly
      increase the elongation rate of petioles under water this species can ameliorate
      flooding stress. However, when leaf blades of R. sceleratus were unable to reach
      the water surface, this species died as quickly as the flooding-intolerant R.
      bulbosus. This indicates that fast elongation of petioles under water competes
      for energy and respirable reserves with maintenance processes. R. repens, a
      species from lower, frequently inundated floodplains, was very tolerant of
      prolonged waterlogging and submergence. Its high resistance to complete
      submergence under continuous darkness indicates that this species tolerates
      hypoxic and/or anoxic tissue conditions via metabolic adjustments. Lysigenous
      aerenchyma was also induced in the primary root system and in newly developed
      laterals, and it was able to use oxygen generated by underwater photosynthesis,
      for root respiration. R. acris, a species from less frequently flooded areas, was
      as resistant to waterlogging and submergence in the light as R. repens. However,
      it has a lower resistance than R. repens to complete submergence in the dark. A
      submergence pre-treatment increased the maximum net underwater photosynthetic
      rate in R. bulbosus, whereas a significant decrease of light compensation points
      was observed in R. repens when it had previously been submerged. This study shows
      that Ranunculus species exhibit various strategies to cope with different
      flooding conditions. R. repens responds to flooding by its tolerance mechanism
      and R. sceleratus by avoidance. R. acris ameliorates submergence and R. bulbosus
      was not able to adapt high water tables.

PMID- 20135155
TI  - Carbon and nitrogen stable isotope ratios in body tissue and mucus of feeding and
      fasting earthworms (Lumbricus festivus).
AB  - We used natural abundance stable isotope techniques to estimate carbon and
      nitrogen turnover rates in body tissue and mucus of earthworms. Isotope ratios of
      carbon (delta(13)C) and nitrogen (delta(15)N) were monitored simultaneously in
      body tissue and mucus for up to 101 days in feeding or fasting Lumbricus festivus
      kept in an artificial substrate. When the diet of the earthworms was switched
      from clover (C(3) plant, legume) to maize (C(4), non-legume), the new dietary
      delta(13)C signature manifested itself much more rapidly in the mucus than in the
      body tissue of the animals, causing a delta(13)C shift of about 4 per thousand in
      mucus and 1 per thousand in tissue after 13.5 days. Turnover of earthworm body
      tissue carbon, unlike that of mucus carbon, was described adequately by an
      exponential, single-pool model. Nitrogen turnover could not be assessed because
      the delta(15)N difference between sources was too small. Fasting for 56 days did
      not result in the expected whole-body (15)N or (13)C enrichment, but it caused a
      significant decrease in mucus and tissue C:N ratios and in the ratio (mucus C:N
      ratio):(tissue C:N ratio). We conclude that the separate analysis of body tissue
      and mucus has great potential for studying the ecophysiology, feeding ecology and
      role in elemental cycling of earthworms and other invertebrates.

PMID- 20135156
TI  - Variably male-biased sex ratio in a marine bird with females larger than males.
AB  - When the costs of rearing males and females differ progeny sex ratios are
      expected to be biased toward the less expensive sex. Blue-footed booby (Sula
      nebouxii) females are larger and roughly 32% heavier than males, thus presumably
      more costly to rear. We recorded hatching and fledging sex ratios in 1989, and
      fledging sex ratios during the next 5 years. In 1989, the sample of 751 chicks
      showed male bias at hatching (56%) and at fledging (57% at 90 days). Fledging sex
      ratios during the five subsequent reproductive seasons were at unity (1 year) or
      male-biased, varying from 56% to 70%. Male bias was greater during years when
      mean sea surface temperature was warmer and food was presumably in short supply.
      During two warm-water years (only) fledging sex ratio varied with hatching date.
      Proportions of male fledglings increased with date from 0.48 to 0.73 in 1994, and
      from 0.33 to 0.79 in 1995. Similar results were obtained when the analysis was
      repeated using only broods with no nestling mortality, suggesting that the
      overall increase in the proportion of males over the season was the result of sex
      ratio adjustments at hatching. The male-biased sex ratio, and the increased male
      bias during poor breeding conditions supports the idea that daughters may be more
      costly than sons, and that their relative cost increases in poor conditions.

PMID- 20135157
TI  - Can extreme morphology in Bosmina reduce predation risk from Leptodora? An
      experimental test.
AB  - Bosmina (Cladocera) populations, especially within the subgenus Eubosmina, show a
      variety of phenotypes that exhibit large differences in body size and shape and
      antennule length. In some populations, the morphological traits also vary during
      the season, with the most extreme forms occurring in periods with high densities
      of certain invertebrate predators. However, while temporal phenotypic variation
      in other cladocerans, as in the family Daphnidae, has been shown to be an
      adaptation to reduce the risk of predation by invertebrate predators, the reason
      for such changes in Bosmina is much less clear. We examined whether certain
      morphological traits in Bosmina species could act as a defence against
      invertebrate predators. We tested three Bosmina forms (subgenus Eubosmina),
      differing in morphology from each other, which are found in lakes together with
      the predator Leptodora kindtii (Cladocera). Bosmina (E.) longispina has a
      relatively low and elongated carapace with a caudal mucro, and short antennule,
      B. (E.) coregoni gibbera has a higher and more protruding carapace without caudal
      mucro, and a much longer antennule. Finally, B. (E.) coregoni retro extensa has a
      carapace like that of B. longispina but with no caudal mucro and a much longer
      antennule. In one experiment, B. longispina and B. gibbera were exposed for 12 h
      to Leptodora in Petri dishes. In a second experiment, we observed directly the
      escape efficiency of B. longispina, B. gibbera and B. retro extensa, and the
      handling time of Leptodora. The two Bosmina forms with more extreme morphological
      features had a lower death rate and higher escape efficiency than B. longispina.
      Prey that escaped did so, in most cases, within 5 min. Predator handling time was
      correlated to predator body length and antennule length of the prey. The results
      suggests that Bosmina species with extreme morphological traits may be less
      vulnerable to invertebrate predators.

PMID- 20135158
TI  - Foraging in a pathogen reservoir can lead to local host population extinction: a
      case study of a Lepidoptera-virus interaction.
AB  - In 1990, natural infestations of the polyphagous vapourer moth, Orgyia antiqua
      (Lepidoptera: Lymantriidae) in lodgepole pine plantations in northern Scotland,
      were studied to ascertain the role of host foraging behaviour on the prevalence
      of nucleopolyhedrovirus (NPV; Baculoviridae) infection in the population. Aerial
      dispersal of early instar larvae (L1-L3) from the tree canopy onto heather
      foliage at the forest understorey, with subsequent relocation back onto the tree
      as late-instar larvae (L4-L6) appeared to play a significant role in the
      development of a widespread virus epizootic in which approximately 80% of L4-L6
      individuals succumbed to disease. Bioassays of foliage 1 year later showed that
      the distribution of NPV followed a pronounced vertical gradient through the
      forest canopy culminating in high concentrations of virus in the forest
      understorey. Experimental systems comprising potted pine trees positioned above
      heather bases showed that NPV infections could be acquired by early stage larvae
      following dispersal from the tree and feeding on the undercanopy vegetation, then
      translocated to the tree component for secondary transmission to susceptible tree
      feeding individuals. Behavioural studies indicated that the tendency for first-,
      second- and third-instar larvae to disperse to the understorey was probably not
      influenced by larval density on the tree but was strongly dependent on larval
      instar. In contrast, the tendency for larvae to relocate from the understorey
      heather to the tree was affected by both larval density and larval instar,
      suggesting that both these factors may significantly affect virus acquisition,
      translocation and transmission in the host population. In the present study, the
      heather understorey appeared to act as a pathogen reservoir in which virus could
      persist between host generations. Spatial heterogeneity in virus distribution
      combined with host foraging behaviour (dispersal and feeding) resulted in the
      pathogen playing a major role in host population dynamics over an extended time
      period (3 years). The reservoir theory is supported by the observation that
      similar dynamics were not observed in O. antiqua populations at neighbouring
      sites which lacked understorey food plants.

PMID- 20135159
TI  - A field study of the effects of elevated CO(2) on plant biomass and community
      structure in a calcareous grassland.
AB  - The effects of elevated CO(2) on plant biomass and community structure have been
      studied for four seasons in a calcareous grassland in northwest Switzerland. This
      highly diverse, semi-natural plant community is dominated by the perennial grass
      Bromus erectus and is mown twice a year to maintain species composition. Plots of
      1.3 m(2) were exposed to ambient or elevated CO(2) concentrations (n = 8) using a
      novel CO(2) exposure technique, screen-aided CO(2) control (SACC) starting in
      March 1994. In the 1st year of treatment, the annual harvested biomass (sum of
      aboveground biomass from mowings in June and October) was not significantly
      affected by elevated CO(2). However, biomass increased significantly at elevated
      CO(2) in the 2nd (+20%, P = 0.05), 3rd (+21%, P = 0.02) and 4th years (+29%, P =
      0.02). There were no detectable differences in root biomass in the top 8 cm of
      soil between CO(2) treatments on eight out of nine sampling dates. There were
      significant differences in CO(2) responsiveness between functional groups
      (legumes, non-leguminous forbs, graminoids) in the 2nd (P = 0.07) and 3rd (P <
      0.001) years of the study. The order of CO(2) responsiveness among functional
      groups changed substantially from the 2nd to the 3rd year; for example, non
      leguminous forbs had the smallest relative response in the 2nd year and the
      largest in the 3rd year. By the 3rd year of CO(2) exposure, large species
      specific differences in CO(2) response had developed. For five important species
      or genera the order of responsiveness was Lotus corniculatus (+271%), Carex
      flacca (+249%), Bromus erectus (+33%), Sanguisorba minor (no significant CO(2)
      effect), and six Trifolium species (a negative response that was not
      significant). The positive CO(2) responses in Bromus and Carex were most closely
      related to increases in tiller number. Species richness was not affected by CO(2)
      treatment, but species evenness increased under elevated CO(2) (modified Hill
      ratio; P = 0.03) in June of the 3rd year, resulting in a marginally significant
      increase in species diversity (Simpson's index; P = 0.09). This and other
      experiments with calcareous grassland plants show that elevated atmospheric CO(2)
      concentrations can substantially alter the structure of calcareous grassland
      communities and may increase plant community biomass.

PMID- 20135160
TI  - Nutrient efficiency along nutrient availability gradients.
AB  - The validity of nutrient use efficiency as a central concept in ecosystem ecology
      has recently been subject to challenge based upon arguments over autocorrelation
      of data, interpretation of graphical approaches, and appropriate statistical
      analyses. Much of the confusion on the measurement and interpretation of nutrient
      use efficiency results from the lack of a sound theoretical basis with which to
      examine experimental results. In this paper, we develop a theory of nutrient use
      efficiency based upon fundamental mass balance, present a graphical approach to
      appropriate testing of alternative hypotheses to avoid problems of
      autocorrelation in data, and suggest critical areas where experiments must be
      performed to distinguish among hypotheses. We show that nutrient use efficiency
      (production per unit nutrient uptake) must be distinguished from nutrient
      response efficiency (production per unit nutrient available). In contrast to the
      monotonic increase of nutrient use efficiency with decreasing nutrient
      availability originally proposed in the 1982 model of P.M. Vitousek, nutrient
      response efficiency is unimodal with maximum efficiency at intermediate levels of
      nutrient availability. However, nutrient use efficiency dynamics at low nutrient
      availability cannot yet be theoretically defined. We also show theoretically
      which plant traits control responses of ecosystem nutrient use or nutrient
      response efficiency along gradients of nutrient availability. Finally, we show
      how our model naturally leads to species replacement along nutrient availability
      gradients.

PMID- 20135161
TI  - Intra- and interspecific host discrimination by host-seeking larvae of
      coleopteran parasitoids.
AB  - Intraspecific host discrimination is widespread in solitary parasitoids whose
      adult females forage for and evaluate host suitability, whereas interspecific
      discrimination is less common. In some parasitoid species, mostly Diptera and
      Coleoptera, the larva performs the last step of host searching. It has been
      suggested that host discrimination will rarely occur in such host-seeking larvae
      because their low mobility results in a low host encounter rate. We determined
      the extent to which the larvae of Aleochara bilineata Gyllenhal (Coleoptera:
      Staphylinidae), a solitary parasitoid of aggregated Diptera pupae: (1)
      discriminated between unparasitized hosts and hosts parasitized by conspecifics;
      (2) used semiochemical cues to discriminate; (3) were influenced by life
      expectancy, presence of conspecifics and host availability in their host
      acceptance decision; and the extent to which (4) A. bilineata and A. bipustulata
      L., a species exploiting the same hosts and occurring sympatrically, showed
      interspecific host discrimination. A. bilineata larvae were able to discriminate
      between unparasitized hosts and hosts parasitized by conspecifics in a choice
      experiment. Such behavior has never previously been described for a coleopteran
      parasitoid or for a parasitoid species whose larvae perform host searching. Host
      discrimination in this species was not based on the presence of visual or tactile
      cues (e.g., entrance holes) but rather on chemical cues. The life expectancy of
      A. bilineata larvae was significantly shorter in the presence than in absence of
      hosts, and older larvae had lower parasitism success than young larvae in a 24-h
      experiment. However, the host acceptance decision of A. bilineata larvae was not
      influenced by larval age or the presence of conspecifics when the ratio of hosts
      per larva was greater than or equal to 1. When hosts were scarce, the degree of
      superparasitism increased significantly with the number of foraging conspecifics
      and the age of the larvae. Both species of Aleochara showed intra- and
      interspecific host discrimination in a choice experiment. In contrast to A.
      bipustulata, A. bilineata larvae more frequently parasitized hosts parasitized by
      A. bipustulata than those parasitized by conspecifics. We suggest that host
      discrimination will be frequent in solitary parasitoids with host-seeking larvae
      when hosts are aggregated.

PMID- 20135162
TI  - Resource competition and suppression of plants colonizing early successional old
      fields.
AB  - Early colonizing annual plants are rapidly suppressed in secondary succession on
      fertile midwestern old fields, while later colonizing perennials persist.
      Differences in competitive ability for above- and belowground resources may be
      partly responsible for differences in species persistence during succession, as
      both light and nutrient availability may change rapidly. We found that, although
      both above- and belowground competition suppress growth of colonizing plants,
      belowground competition was the dominant factor in the suppression of the annual
      Ambrosia artemisiifolia in 2nd-year-old fields near the W.K. Kellogg Biological
      Station in southwestern Michigan. Despite an ability to persist in later
      successional fields, seedling transplants of the perennial Achillea millefolium
      were also suppressed by above- and belowground competition, with belowground
      competition having the strongest effect. As in many old fields, nitrogen
      availability is the primary factor limiting plant productivity. There was no
      clear difference between the species in ability to compete for (15)N from an
      enriched patch, although there was an indication of greater precision of foraging
      by Achillea. Life history differences between these species and consequent
      differences in the phenology of root growth relative to other old-field plants
      are likely to play a large role in the persistence of Achillea in successional
      fields where Ambrosia is suppressed.

PMID- 20135163
TI  - Settlement and recruitment of three damselfish species: larval delivery and
      competition for shelter space.
AB  - Spatial patterns of settlement and abundance of older life stages were examined
      for three species of damselfish in the genus Dascyllus by monitoring natural
      colonization of standard amounts of initially empty juvenile microhabitat
      (anemones for D. trimaculatus; branching coral for D. flavicaudus and D. aruanus)
      transplanted to a series of sites within lagoons of Moorea, French Polynesia.
      Large spatial differences in larval colonization were observed, which were
      temporally consistent but different among the species. At the whole-island scale,
      D. trimaculatus settled primarily on the northern shore, while settlement of the
      other two species was greatest at the southern end. The three species also showed
      different patterns of settlement within lagoons: D. aruanus settled mainly nearer
      to shore, D. flavicaudus primarily on offshore lagoon portions and D.
      trimaculatus colonized equally across the lagoons. Among sites around the island,
      the relative abundance of older juveniles after 10 months was a curvilinear
      function of the relative abundance of settlers for two species (D. trimaculatus
      and D. flavicaudus). There was no relationship between patterns of settlement and
      abundance of older juveniles for D. aruanus, although juvenile abundance was
      inversely related to that of juvenile D. flavicaudus. At the within-lagoon scale,
      settlement mirrored almost exactly the relative abundance of older lifestages of
      D. trimaculatus and D. flavicaudus, whereas there was just a qualitative match
      for D. aruanus. A competition experiment revealed that juvenile D. flavicaudus
      had a greater effect on population growth of D. aruanus than vice versa, and this
      mechanism helped explain why the modification of settlement patterns was greatest
      in D. aruanus. Interspecific variation in abundance of older stages was shaped to
      differing extents by both patterns of larval delivery and subsequent density
      dependent processes involving competition for shelter space.

PMID- 20135164
TI  - Effects of patch size on colonisation in estuaries: revisiting the species-area
      relationship.
AB  - The effects of patch size on the colonisation and succession of intertidal
      invertebrates and algae were investigated in an estuary near Sydney, New South
      Wales, Australia. The specific aim was to test explicitly for the presence of a
      species-area relationship, and examine whether this could be explained by the
      random placement hypothesis (i.e. that the number of species per unit area was
      the same on patches of different sizes). In addition, I tested the extent to
      which differences in numbers of species reflected differences in the composition
      of assemblages. Wooden panels of three different sizes (10 x 10 cm, 20 x 20 cm
      and 40 x 40 cm) were placed in the field on intertidal oyster leases in each of
      two different experimental trials: spring (October 1994) and summer (January
      1995). Independent replicate measures of the number of colonising species on
      panels were obtained after different periods of time, up to 25 months. I also
      obtained measures of abundance of individual species and composition of
      assemblages on panels of different sizes. This allowed specific tests of the
      hypothesis that the size of the patch being colonised is important in structuring
      these assemblages. The strength of the species-area relationship increased
      through time on panels submersed in October, but the trend was reversed for
      panels submersed in January. There was a significant interaction between factors
      of patch size and time of submersion for multivariate measures of differences in
      composition among replicates. The random placement hypothesis was supported in
      certain situations, but not in others. When rejected, it was for different
      reasons on panels submersed in the two different trials. Panels initiated in
      October tended to have proportionally greater numbers of species per unit area on
      larger panels, while the panels initiated in January tended to have more species
      per unit area on smaller panels. There was an identifiable relationship between
      differences in numbers of species and differences in species composition for
      panels submersed in October. This was not true, however, for panels submersed in
      January, where the species-area relationship did not hold after longer periods.
      The succession of organisms through time was, overall, more important in
      structuring the assemblages than was the size of the patch being colonised. The
      species-area relationship should not necessarily be regarded as a truism - it did
      not always hold in this system. The initial timing of experiments with respect to
      recruitment and succession influenced the results.

PMID- 20135165
TI  - Effects of drift- and benthic-foraging fish on the drift dispersal of three
      species of mayfly nymphs in a Japanese stream.
AB  - Differences in the effects of two common predatory fishes, rainbow trout
      (Oncorhynchus mykiss) and freshwater sculpin (Cottus nozawae), on drift dispersal
      of the nymphs of three mayfly species, Baetis thermicus, Cinygmula sp., and
      Paraleptophlebia chocorata, were examined by manipulative field experiments using
      stream enclosures in a northern Japanese stream. The diel periodicity of prey
      consumption rate differed considerably between the two fishes; the prey
      consumption of the drift-foraging trout was greater at both dawn and dusk,
      whereas the benthic-foraging sculpin showed a higher consumption rate at night.
      The drift propensity at night was much greater than during the day for all the
      mayfly species in each of the trout, sculpin and fishless treatments, as well as
      under natural conditions with both fishes present. The nighttime drift
      propensities of the epibenthic grazers, B. thermicus and Cinygmula sp., were
      greater in the sculpin treatment than in trout and fishless treatments, and they
      did not differ between the trout and fishless treatments. By contrast, the
      nighttime drift propensity of P. chocorata, an infaunal collector-gatherer, did
      not differ among the treatments. The daytime drift propensity did not differ
      among the treatments for any of the mayfly species. Thus differences in drift
      response to the predatory fishes could be related to the characteristic
      microhabitats of the mayfly species. Moreover, the experiments demonstrated that
      benthic-foraging sculpin had greater overall effects on prey drift than drift
      foraging trout.

PMID- 20135168
TI  - The effect of mechanical ventilation tidal volume during pneumoperitoneum on
      shoulder pain after a laparoscopic appendectomy.
AB  - BACKGROUND: Postlaparoscopic shoulder pain (PLSP) frequently occurs after various
      laparoscopic surgical procedures. Its mechanism is commonly assumed to be
      overstretching of the diaphragmatic muscle fibers due to the pressure of a
      pneumoperitoneum, which causes phrenic nerve-mediated referred pain to the
      shoulder. Based on this hypothesis, we speculated that during inspiration, the
      lung could squeeze out the phrenic nerve with carbon dioxide gas against the
      constantly pressurized abdominal cavity with increasing tidal volume (V(T)).
      Thus, we examined whether mechanical ventilation with a low V(T) (LTV, V(T) 7
      ml/kg) during a pneumoperitoneum might reduce PLSP in patients undergoing
      laparoscopic appendectomy compared with ventilation with the traditional V(T)
      (TTV, V(T) 10 ml/kg). METHODS: In a prospective trial, 64 adult patients
      undergoing laparoscopic appendectomy were randomly assigned to two groups of 32
      each (LTV and TTV groups). Intravenous ketorolac was used as a postoperative
      rescue analgesic. The 2-, 4-, 24-, and 48-h postoperative incidence and severity
      of PLSP, severity of surgical pain, and need for rescue analgesia was assessed.
      RESULTS: The overall incidence of PLSP was similar in both groups (57.1% in the
      LTV group vs. 65.5% in the TTV group). Compared with the TTV group, the incidence
      and PLSP verbal rating scale (VRS) did not decrease in the LTV group throughout
      the study period. No statistically significant differences were observed in the
      VRS surgical pain score, the cumulative ketorolac consumption at each time point,
      or the time to first rescue analgesia. CONCLUSIONS: Mechanical ventilation with a
      reduced 7 ml/kg V(T) during a pneumoperitoneum does not reduce the frequency and
      severity of PLSP after laparoscopic appendectomy compared with ventilation with
      the traditional V(T) (10 ml/kg).

PMID- 20135169
TI  - Re: Single incision multiport laparoendoscopic (SIMPLE) surgery.

PMID- 20135170
TI  - Effort, safety, and findings of routine preoperative endoscopic evaluation of
      morbidly obese patients undergoing bariatric surgery.
AB  - BACKGROUND: Obesity is becoming an epidemic health problem and is associated with
      concomitant diseases, such as sleep apnea syndrome and gastroesophageal reflux
      disease (GERD). There is no standardized diagnostic workup for the upper
      gastrointestinal tract in obese patients; many patients have no upper
      gastrointestinal symptoms, and few data are available on safety of endoscopy in
      morbidly obese patients. METHODS: Sixty-nine consecutive diagnostic upper
      gastrointestinal endoscopies in morbidly obese patients (26 men, 43 women; mean
      age 43.4 +/- 10.9 years) were prospectively evaluated from January to December
      2008 in an outpatient setting before bariatric procedures. Sedation was
      administered with propofol. Data on sedation, critical events, and examination
      times were recorded, as well as pathological findings. RESULTS: The patients'
      mean body mass index was 47.6 +/- 7.9 (range, 35.1-73.3) kg/m(2); 17.4% reported
      GERD symptoms. The mean duration of the endoscopy procedure (including sedation)
      was 20.3 +/- 9.3 (range, 5-50) min, and the whole procedure (including
      preparation and postprocessing) took 58.2 +/- 19 (range, 20-120) min. The mean
      propofol dosage was 380 +/- 150 (range, 80-900) mg. Two patients had critical
      events that required bronchoscopic intratracheal O(2) insufflation due to severe
      hypoxemia (<60% SaO: (2)). Nearly 80% of patients had pathological findings in
      the upper gastrointestinal tract. Only 20% reported upper gastrointestinal
      symptoms. Pathologic conditions were found in the esophagus in 23.2% of the
      patients, in the stomach in 78.2%, and in the duodenum in 11.6%. The prevalence
      of Helicobacter pylori infection was 8.7%. CONCLUSIONS: Upper gastrointestinal
      endoscopy can be performed safely. However, careful monitoring and
      anesthesiological support are required for patients with concomitant diseases and
      those receiving sedation. Because 80% of the patients with pathological findings
      were asymptomatic, every morbidly obese patient should undergo endoscopy before
      bariatric surgery because there may be findings that might change the surgical
      strategy.

PMID- 20135171
TI  - Risk-sensitive events during laparoscopic cholecystectomy: the influence of the
      integrated operating room and a preoperative checklist tool.
AB  - BACKGROUND: Awareness of the relative high rate of adverse events in laparoscopic
      surgery created a need to safeguard quality and safety of performance better.
      Technological innovations, such as integrated operating room (OR) systems and
      checklists, have the potential to improve patient safety, OR efficiency, and
      surgical outcomes. This study was designed to investigate the influence of the
      integrated OR system and Pro/cheQ, a digital checklist tool, on the number and
      type of equipment- and instrument-related risk-sensitive events (RSE) during
      laparoscopic cholecystectomies. METHODS: Forty-five laparoscopic
      cholecystectomies were analyzed on the number and type of RSE; 15 procedures were
      observed in the cart-based OR setting, 15 in an integrated OR setting, and 15 in
      the integrated OR setting while using Pro/cheQ. RESULTS: In the cart-based OR
      setting and the integrated OR setting, at least one event occurred in 87% of the
      procedures, which was reduced to 47% in the integrated OR setting when using
      Pro/cheQ. During 45 procedures a total of 57 RSE was observed-most were caused by
      equipment that was not switched on or with the wrong settings. In the integrated
      OR while using Pro/cheQ the number of RSE was reduced by 65%. CONCLUSIONS: Using
      both an integrated OR and Pro/cheQ has a stronger reducing effect on the number
      of RSE than using an integrated OR alone. The Pro/cheQ tool supported the optimal
      workflow in a natural way and raised the general safety awareness amongst all
      members of the surgical team. For tools such as integrated OR systems and
      checklists to succeed it is pivotal not to underestimate the value of the
      implementation process. To further improve safety and quality of surgery, a
      multifaceted approach should be followed, focusing on the performance and
      competence of the surgical team as a whole.

PMID- 20135172
TI  - A prospective randomized trial comparing two-stage versus single-stage management
      of patients with gallstone disease and common bile duct stones.
AB  - BACKGROUND: The optimal management of patients with concomitant common bile duct
      stones and gallstones is still evolving. With the introduction of laparoscopic
      common bile duct exploration, many centers prefer single-stage laparoscopic
      cholecystectomy and common bile duct exploration over preoperative endoscopic
      bile duct clearance followed by laparoscopic cholecystectomy. The present study
      was done to compare these two management options. PATIENTS AND METHODS: 30
      patients with symptomatic gallstones and common bile duct stones were randomized
      to either treatment option. Preoperative endoscopic ultrasound (EUS) and/or
      magnetic resonance pancreaticography (MRCP) was done in all patients to confirm
      the diagnosis. In group I, laparoscopic cholecystectomy and common bile duct
      exploration was done at the same sitting; in group II, endoscopic stone clearance
      was followed by laparoscopic cholecystectomy 4-6 weeks later. Success was defined
      as successful treatment by the intended modality. RESULTS: 15 patients were
      randomized to each group and the two groups had comparable demographic and
      clinical profile. In group I there was a success rate of 93.5% in comparison with
      86.7% in group II (p = 0.32, Fisher's exact test). The complications were similar
      in the two groups. CONCLUSIONS: The results showed equivalent success rate in
      terms of morbidity and hospital stay. Laparoscopic approach seems to be favorable
      because of the smaller number of procedures and hospital visits.

PMID- 20135173
TI  - Stapled transanal rectal resection for symptomatic intussusception: morphological
      and functional outcome.
AB  - INTRODUCTION: Stapled transanal rectal resection (STARR) was developed to correct
      intussusception causing obstructed defecation. Some patients, however, do not
      profit from this operation as anticipated. We aimed to study the relationship
      between functional outcome and rectal morphology after STARR. METHODS: Fifteen
      consecutive female patients with median age of 64 years [interquartile range
      (IQR) 58-71 years] were studied before and after STARR. All patients had symptoms
      of obstructed defecation preoperatively. Pre- and postoperative workup consisted
      of standardized interview (including Wexner score) with physical examination
      including procto- and rectoscopy, anorectal manometry, and magnetic resonance
      (MR) defecography. Median follow up was 18 months (IQR 16-22 months). RESULTS:
      STARR was technically successful in all 15 patients without intra- or
      postoperative complications. Median (IQR) Wexner score of fecal incontinence was
      0 (0-0) before and 3 (0-4.5) after surgery (p < 0.05). While all patients had
      repetitive incomplete defecation preoperatively, this symptom was present in
      seven patients postoperatively (p < 0.01). Third-degree intussusception was
      diagnosed during MR defecography in all patients preoperatively. After surgery,
      no patient had third-degree intussusception but one patient had first-degree and
      one patient had second-degree intussusception (p < 0.05). Size of rectocele was
      reduced from 2.9 cm (2.0-3.8 cm) to 0.8 cm (0.6-1.9 cm) (p < 0.05). Sphincter
      pressures were unchanged during anorectal manometry; however, first sensation
      during balloon distension in the rectum decreased from 50 ml (40-83 ml) before
      surgery to 30 ml (25-40 ml) after surgery (p < 0.05). CONCLUSION: Stapled
      transanal rectal resection (STARR) achieved a high rate of morphological
      correction of intussusception; however, symptoms of obstructed defecation were
      not improved to the same extent, which warrants exploration in future studies.

PMID- 20135174
TI  - Extraluminal laparoscopic wedge resection of gastric submucosal tumors: a
      retrospective review of 84 cases.
AB  - BACKGROUND: Laparoscopic resection of gastric stromal tumors is being performed
      with increased frequency. This study aims to evaluate the feasibility and safety
      of the extraluminal laparoscopic gastric wedge resection (ELWR) technique.
      METHODS: Clinical data of 84 patients who underwent ELWR for gastric submucosal
      tumors between September 2000 and December 2007 were reviewed and analyzed
      retrospectively. The operation includes: localization of the tumor, dissection of
      the omentum, mobilization of the upper stomach and the upper pole of the spleen,
      exposure of esophago-cardiac junction (ECJ), and wedge resection of the upper
      part of gastric body and/or the gastric fundus with endoscopic gastrointestinal
      anastomosis (Endo GIA) stapler. RESULTS: All of the procedures were performed
      successfully, with mean operation time of 62.6 +/- 8.9 min and mean
      intraoperative blood loss of 86.2 +/- 8.1 ml. Through extraluminal laparoscopic
      wedge resection, complete R0 resection was achieved for all tumors. All surgical
      margins were negative microscopically. No lesions were missed, nor were there any
      significant postoperative complications or intraoperative conversions to open
      surgery. A total of 78.6% of the patients recovered their gastrointestinal
      functions and began to eat and ambulate within 36 h of the operation. The
      smallest surgical margins were 0.7-2.5 cm, with a mean distance of 1.4 +/- 0.5
      cm. Of the 84 cases of gastric submucosal tumors, 29 cases were leiomyomas, 51
      cases were various types of stromal tumors, and 4 other cases were neurofibromas.
      Mean follow-up duration was 51 +/- 4.3 months (overall follow-up rate 73.8%,
      62/84 cases), during which no recurrences or metastases were found. CONCLUSION:
      ELWR is a safe, simple, and effective procedure for treating submucosal tumors in
      the upper part of the stomach. It can avoid intraperitoneal contamination,
      possible tumor spillage, and postoperative esophageal stenosis, and provides
      unlimited scope for gastric resection.

PMID- 20135175
TI  - Detection of gastric conduit ischemia or anastomotic breakdown after cervical
      esophagogastrostomy: the use of computed tomography scan versus early endoscopy.
AB  - BACKGROUND: Concern over potential injury to the anastomosis has limited the use
      of early postoperative endoscopy to diagnose conduit ischemia or anastomotic
      breakdown. Alternatively, a computed tomography (CT) scan has been suggested as a
      noninvasive means for identifying these complications. This study aimed to
      compare CT scan with early endoscopy for diagnosing gastric conduit ischemia or
      anastomotic breakdown after esophagectomy with cervical esophagogastrostomy.
      METHODS: Between 2000 and 2007, 554 patients underwent an esophagectomy and
      gastric pull-up with cervical esophagogastrostomy at the University of Southern
      California. Records were reviewed to identify patients who had undergone
      endoscopy and CT scan within 24 h of each other during the first three
      postoperative weeks for suspicion of an ischemic conduit or anastomotic
      breakdown. The accuracies of CT scan and endoscopy in diagnosing an ischemic
      conduit were compared. RESULTS: A total of 76 patients had endoscopy and CT scan
      for clinical suspicion of conduit ischemia or anastomotic breakdown. Endoscopy
      was performed without complications in all 76 patients. The postoperative
      endoscopic findings were normal in 24 of the patients, and none subsequently
      experienced an ischemic conduit or anastomotic breakdown. Evidence of ischemia
      was present in 28 patients, 7 of whom had black mucosa throughout the gastric
      conduit with the anastomosis still intact and required removal of their conduit.
      The remaining 24 patients had partial or complete anastomotic breakdown. On the
      CT scan, 23 of the 76 patients showed evidence of conduit ischemia (n = 9) or
      anastomotic breakdown (n = 14). There was no evidence of ischemia or anastomotic
      breakdown on CT scan for the 24 patients with normal endoscopy or for 3 of the 7
      patients who had their conduit removed for graft necrosis. CONCLUSION: A normal
      CT scan does not rule out the possibility of an ischemic gastric conduit after
      esophagectomy. Early endoscopy is a safe and accurate method for assessing
      conduit ischemia.

PMID- 20135176
TI  - Suprapapillary needleknife fistulotomy: a safe and effective method for accessing
      the biliary system.
AB  - BACKGROUND: Suprapapillary needleknife fistulotomy is performed when standard
      biliary cannulation methods have failed. However, its role is controversial, with
      conflicting reports on its use. This study aimed to determine the efficacy and
      safety of needleknife fistulotomy after failure of conventional cannulation
      techniques. METHODS: All patients who underwent needleknife fistulotomy were
      identified from a single tertiary referral center database prospectively
      maintained from 1997 to 2007. RESULTS: A total of 2,603 patients underwent
      endoscopic retrograde cholangiopancreatography (ERCP) over the 10-year period.
      Fistulotomy was performed for 352 patients (13.5%), with 317 of these patients
      (90.1%) experiencing successful biliary cannulation. With the use of fistulotomy,
      the total cannulation success rate increased from 79.0 to 91.2% (P < 0.0001).
      Endoscopic management of choledocholithiasis and hepatobiliary malignancy
      increased from 48.9 to 55.1% (P < 0.001), and from 12.0 to 16.0% (P < 0.001) for
      all cases. The complication rate was significantly higher for the patients who
      underwent fistulotomy than for those who did not (4.8% vs. 2.1%; P < 0.001),
      which can be explained by a higher rate of mild bleeding in the fistulotomy
      group. However, no significant difference in pancreatitis or perforation between
      the two groups was observed. In addition, no fatalities occurred after
      fistulotomy. CONCLUSION: Suprapapillary needleknife fistulotomy is an effective
      method for accessing the biliary system after failed standard cannulation.
      Despite a higher rate of mild bleeding, fistulotomy was not associated with an
      increased risk of serious complications.

PMID- 20135177
TI  - Laparoscopic surgery for rectal cancer: the standard of care?

PMID- 20135178
TI  - Technique of open laparoscopy for supramesocolic surgery in obese patients.
AB  - BACKGROUND: Incidence of obesity and related diseases are increasing in the
      world. Visceral surgeons are more often confronted with laparoscopic surgery in
      obese patients. Besides validated surgery procedures, such as cholecystectomy and
      gastroesophageal reflux surgery, bariatric procedures are increasingly performed.
      In obese patients, the thickness of adipose panicle makes open laparoscopy
      hazardous. METHODS: In our department, we use systematically a technique of open
      laparoscopy in obese patients for supramesocolic surgery, which is safe,
      reproducible, and permits good closure of the abdominal wall. RESULTS: The
      surgical technique consists of opening the abdominal wall through the rectus
      abdominis. Helped by specific retractors called Descottes (Medtronic Laboratory),
      both fascias are charged by sutures separately. Incision in the fascias is made
      safely by pooling on sutures. Introduction of port-site is made under view
      control. At the end of laparoscopy, closure of both fascias is easily done.
      CONCLUSIONS: We present a technique of open laparoscopy in obese patients,
      systematically used, for supramesocolic surgery. This technique is safe,
      reproducible, and permits an efficient closure of the abdominal wall.

PMID- 20135179
TI  - Safety of the laparoscopic adjustable gastric band: 7-year data from a U.S.
      center of excellence.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has become one of the
      most common weight-loss procedures performed in the United States. The authors'
      high-volume academic medical center has gathered a database of almost 3,000
      patients who have undergone LAGB since January 2001. The goal of this series, the
      largest to date on LAGB outcomes at a single institution, was to assess
      complications associated with LAGB. METHODS: A retrospective analysis was
      performed using longitudinal data from adult patients who underwent LAGB between
      1 January 2001, and 29 February 2008. General and band-related complications were
      reported for all patients. Death and reoperation for weight gain (LAGB followed
      by either a second band insertion or a gastric bypass) also were reported.
      RESULTS: Of the 2,965 patients who received LAGB during the study period, 2,909
      met the criteria for inclusion in this analysis, and 363 (12.2%) experienced one
      or more complications. The most common complications were band slip (4.5%) and
      port-related problems (3.3%). Other complications were rare. Only seven patients
      (0.2%) had band erosion. Eleven patients (0.4%) underwent reoperation for weight
      gain. A total of 10 deaths (0.34%) occurred during the study period. Three
      patients died within 30 days of surgery. Two of these deaths (0.06%) were related
      to surgery, and one resulted from a motor vehicle accident. Seven patients died
      of causes unrelated to surgery during the course of the study. CONCLUSIONS: The
      LAGB technique is a relatively safe procedure with few early or late
      complications. Few LAGB patients undergo reoperation for weight gain, and
      mortality is very rare.

PMID- 20135180
TI  - Single-port-access (SPA) cholecystectomy: a multi-institutional report of the
      first 297 cases.
AB  - BACKGROUND: An important aspect of a new surgical technique is whether it can be
      performed by other surgeons in other institutions. The authors report the first
      297 cases in a multi-institutional and multinational review of laparoscopic
      cholecystectomy performed via a single portal of entry. METHODS: Data were
      collected retrospectively for the initial patients undergoing single-port
      cholecystectomy by 13 surgeons who performed these procedures in their
      institutions after training by the authors. The review included operative time,
      blood loss, incision length, length of hospital stay (LOS), necessary additional
      trocars, and other parameters important to cholecystectomy. A database of all the
      single-port-access (SPA) surgeries performed by the surgeons included demographic
      and procedural details, LOS, complications, and initial follow-up data. RESULTS:
      To date, 297 single-port cholecystectomies have been performed for a variety of
      diagnoses, primarily cholelithiasis. The average operative time was 71 min, and
      the average LOS was 1-2 days. The average blood loss was minimal. The use of
      additional port sites outside the umbilicus occurred in 34 of the cases. Of the
      35 intraoperative cholangiograms performed, 34 were successful. No significant
      complications occurred except for seromas and minor postoperative wound
      infections. These results are comparable with those for standard multiport
      cholecystectomy. In addition, no access site hernias (ASH) occurred. CONCLUSIONS:
      The findings demonstrate that SPA surgery is an alternative to multiport
      laparoscopy with fewer scars and better cosmesis. One factor affecting the rate
      for adoption of SPA surgery among other surgeons is the reproducibility of this
      new procedure. Although this study had insufficient data to determine fully the
      benefits of SPA surgery, the feasibility of this procedure with safe, acceptable
      results was demonstrated in this initial large series across multinational
      institutions.

PMID- 20135181
TI  - Is unilateral laparoscopic TEP inguinal hernia repair a job half done? The case
      for bilateral repair.
AB  - INTRODUCTION: Bilateral laparoscopic totally extraperitoneal (TEP) repair of
      unilateral hernia is conspicuous in published literature by its absence. There
      are no studies or data on the feasibility, advantages or disadvantages of
      bilateral repair in all cases or in any subset of patients with unilateral
      primary inguinal hernia. The objective of this study is to investigate the
      feasibility of bilateral laparoscopic exploration for all unilateral cases
      followed by laparoscopic TEP in all cases and to compare complications,
      recurrence rates, postoperative pain, patient satisfaction, and return to work
      retrospectively with a similar number of age-matched retrospective controls.
      METHOD: One hundred fifty TEP operations were performed in 75 patients (group A)
      prospectively and were compared with 75 unilateral TEP operations (group B) in
      age-matched controls done previously by the same surgeon. All cases were
      performed under general anesthesia, and TEP repair was performed using three
      midline ports. All uncomplicated patients were discharged at 24 h, in keeping
      with departmental policy. RESULTS: Of 75 patients (group A), 25 (33.3%) were
      clinically diagnosed with bilateral hernia and the rest (50, 66.66%) with
      unilateral hernia. The distribution of the 25 bilateral cases was 11 bilateral
      direct and 14 bilateral indirect inguinal hernias. The distribution of the 75 age
      matched controls (group B) was all unilateral hernia, of which 47 were right
      sided and 28 were left-sided. There were 23 direct hernias and 52 indirect
      hernias among the control group. The mean operative time for all 150 cases was
      76.66 +/- 15.92 min. The operative time in the control group (unilateral hernias)
      was 66.16 +/- 12.44 min, whereas the operative time in the test group (bilateral
      repair) was 87.2 +/- 11.32 min. The operative time in the bilateral group was
      significantly higher, by 21.04 min or 31.88% (p = 0.000). The operative time in
      the true unilateral group was 82.45 +/- 9.38 min, whereas the operative time in
      the former group [occult contralateral hernias (OCHs) + bilateral hernias] was
      91.35 +/- 11.95 min, which is a statistically significant difference (p =
      0.0015). Occult hernia was seen in a total of 15 cases, of which 13 were OCHs
      (26%) and 2 were occult ipsilateral hernias (OIH). The mean operative time in the
      OCH cases was 81.46 +/- 7.9 min, whereas in those without OCH it was 82.45 +/-
      9.38 min, which is not a statistically significant difference (p = 0.46).
      Regarding complications, there were no cases of seroma, hematoma, wound
      infection, visceral injury or postoperative neuralgia in either group A or B. On
      statistical analysis, visual analog score (VAS)-measured pain score, at 12 h
      only, was significantly higher in the unilateral repair group as compared with
      the bilateral TEP group; VAS scores at all other times were not statistically
      significantly different between the two groups. The average time of return to
      light routine or activities of daily living was 1 day in group A, whereas in
      group B it was 1.91 days (range 1-3 days), which is a statistically significant
      difference (p = 0.000). There was one case of recurrence in this study, in a left
      sided hernia in group A, over a follow-up period of 60-72 (mean 66) months; all
      patients reported for follow-up by office visit or correspondence until 2 years,
      and two patients were lost to follow-up after 2 years. In group B, there was no
      recurrence over a follow-up period of 72-84 months, with three patients lost to
      follow-up after 3 years. CONCLUSION: In the present study bilateral TEP was
      performed in three types of patients: those with clinically bilateral hernias,
      those with clinically unilateral hernia but with an OCH, and in truly unilateral
      hernias. All of these were compared with unilateral TEPs in clinically unilateral
      hernias, and we found no significant increase in morbidity, pain, recurrence or
      complications in bilateral repairs. Convalescence from surgery, as determined by
      return to activities of daily living and return to work parameters, was also
      comparable. Surgeons experienced in laparoscopic TEP, in high-volume centers, can
      provide bilateral repairs in patients with inguinal hernia, bearing in mind its
      advantages and comparable morbidity. We also feel that, in elective repair of
      inguinal hernia, the patient should be given the option of bilateral repair.
      Bilateral repair does not add to the risk of surgery in experienced hands and we
      strongly feel that unilateral TEP is actually a job half done.

PMID- 20135182
TI  - Thoracoscopic robot-assisted extended thymectomy in the human cadaver.
AB  - METHODS: Thoracoscopic robot-assisted extended thymectomy was performed in a
      human cadaver. The technique utilized the da Vinci surgical system inserted
      through the subxiphoid approach with the sternum lifted upward (anteriorly). A
      small subxiphoid incision and two additional thoracoports were made in the chest
      wall, and the sternum was lifted by a new lifting retractor system. RESULTS: This
      method provided sufficient view and working space in the anterior mediastinum. A
      complete thymectomy was performed with facility. The robotic system provides
      superior optics and allows for enhanced dexterity. CONCLUSIONS: Minimally
      invasive robotic-assisted thymectomy is an effective procedure and may add
      benefits for both surgeon and patients.

PMID- 20135183
TI  - Commentary on: T. Sinnett, N. Karanjia (2009) Decompression of a pneumoperitoneum
      during a total extraperitoneal (TEP) inguinal hernia repair by incision of the
      umbilical sac under direct vision.

PMID- 20135184
TI  - Psychogenic axial myoclonus: report on two cases.
AB  - Axial myoclonus (AM) is characterized by sudden muscle jerks involving axial and
      proximal muscles. It includes propriospinal myoclonus (PSM) which consists of
      trunk flexion or extension jerking with activity arising in axial muscles and
      spreading to caudal and rostral muscles at low velocity along propriospinal
      pathways. We report on two patients displaying flexion AM jerks in the absence of
      structural lesion of the central nervous system or electrophysiological evidence
      of organic origin. A conversion disorder was diagnosed. The jerks disappeared
      after psychoeducation with the patients remaining symptom free in 6-year long
      follow-up. The diagnoses of psychogenic axial (propriospinal-like) myoclonus were
      established. The literature on psychogenic axial (propriospinal-like myoclonus)
      is limited to a case report. Our cases demonstrate a good response to
      psychotropic medication and psychoeducation and fulfill the psychogenic movement
      disorder criteria. The phenomenology of psychogenic abnormal movements is diverse
      and PSM-like clinical picture may be a novel presentation.

PMID- 20135185
TI  - Intraoperative microrecordings in the posterior hypothalamus of anaesthetized
      humans with aggressive behaviour.
AB  - Two patients with uncontrollable aggressive behaviour underwent the placement of
      stimulating leads in the posterior hypothalamus (pHyp). One patient had also
      multifocal refractory epilepsy. Microrecordings were obtained in both patients
      during surgery under general anaesthesia. Firing rate, interspike intervals and
      oscillatory discharge patterns were analysed in 14 neurons. A mean discharge rate
      of 19 Hz, and oscillatory activity at 7-8 Hz were recorded in the first patient
      with aggressiveness and epilepsy. In the second patient the mean firing rate was
      10 Hz, with evidence of both tonic and random firing patterns. Previous studies
      in patients with cluster headache showed that a discharge rate around 20 Hz and
      lack of a specific rhythmic pattern were the most consistent characteristics of
      neuronal discharge in this area. Our present findings therefore would suggest
      that the pattern of discharge of neurons in the pHyp should be evaluated with
      reference to the presence of concurrent pathology.

PMID- 20135186
TI  - Lemierre syndrome: report of five new cases and literature review.
AB  - Lemierre Syndrome (LS) is relatively rare, and its clinical features are
      potentially confusing. Without proper therapy, LS is associated with significant
      morbidity and is potentially fatal. Recognition of the imaging features of LS in
      the chest and the neck may permit a timely diagnosis and lead to prompt
      institution of appropriate therapy. The emergency imaging features of LS in five
      cases are reviewed with emphasis on computed tomography of the chest and neck.

PMID- 20135187
TI  - Association of stem cell marker CD133 expression with dissemination of
      glioblastomas.
AB  - Dissemination of glioblastoma was once considered rare but is now increasingly
      encountered with longer survival of glioblastoma patients. Despite the potential
      negative impact of dissemination on clinical outcome, however, molecular markers
      useful for prediction of dissemination risk still remains ill defined. We tested
      in this study for an association between the expression of stem cell marker CD133
      and the risk of dissemination in 26 cases of glioblastoma (16 with dissemination
      and 10 without dissemination). The protein expression of CD133 was examined by
      western blot analysis of tumor specimens, and the CD133 expression levels were
      quantified by densitometry and normalized to beta-actin. The results indicated
      that CD133 expression levels are significantly higher in glioblastomas with
      dissemination (mean 10.3, range 0.20-27.8) than in those without (mean 1.18,
      range 0.07-3.58). The results suggest that CD133 could be a molecular predictor
      of glioblastoma dissemination, and also give rise to an intriguing idea that
      CD133-positive cancer stem cells may be implicated in the initiation of
      disseminated lesions.

PMID- 20135188
TI  - Transvaginal specimen extraction in a laparoscopic anterior resection of a
      sigmoid colon neoplasia with en bloc right salpingo-oophorectomy.
AB  - Laparoscopic colorectal surgery has well-known benefits. However, an abdominal
      incision, albeit much smaller than conventional surgery, is still needed. A
      transvaginal extraction of a sigmoid colon neoplasia with en bloc salpingo
      oophorectomy and colorectal mechanical anastomosis is described. The technique is
      feasible and safe. The excellent recovery of the 86-year-old patient shows the
      potential future of the natural orifices endoscopic surgery.

PMID- 20135189
TI  - Inequalities in the use of health services between immigrants and the native
      population in Spain: what is driving the differences?
AB  - In Spain, a growing body of literature has drawn attention to analysing the
      differences in health and health resource utilisation of immigrants relative to
      the autochthonous population. The results of these studies generally find
      substantial variations in health-related patterns between both population groups.
      In this study, we use the Oaxaca-Blinder decomposition technique to explore to
      what extent disparities in the probability of using medical care use can be
      attributed to differences in the determinants of use due to, e.g. a different
      demographic structure of the immigrant collective, rather than to a different
      effect of health care use determinants by nationality, holding all other factors
      equal. Our findings show that unexplained factors associated to immigrant status
      determine to a great extent disparities in the probability of using hospital,
      specialist and emergency services of immigrants relative to Spaniards, while
      individual characteristics, in particular self-reported health and chronic
      conditions, are much more important in explaining the differences in the
      probability of using general practitioner services between immigrants and
      Spaniards.

PMID- 20135190
TI  - Sensitivity analysis and parametric study of elastic properties of an
      unidirectional mineralized bone fibril-array using mean field methods.
AB  - The key parameters determining the elastic properties of an unidirectional
      mineralized bone fibril-array decomposed in two further hierarchical levels are
      investigated using mean field methods. Modeling of the elastic properties of
      mineralized micro- and nanostructures requires accurate information about the
      underlying topology and the constituents' material properties. These input data
      are still afflicted by great uncertainties and their influence on computed
      elastic constants of a bone fibril-array remains unclear. In this work, mean
      field methods are applied to model mineralized fibrils, the extra-fibrillar
      matrix and the resulting fibril-array. The isotropic or transverse isotropic
      elastic constants of these constituents are computed as a function of degree of
      mineralization, mineral distribution between fibrils and extra-fibrillar matrix,
      collagen stiffness and fibril volume fraction. The linear sensitivity of the
      elastic constants was assessed at a default set of the above parameters. The
      strain ratios between the constituents as well as the axial and transverse
      indentation moduli of the fibril-array were calculated for comparison with
      experiments. Results indicate that the degree of mineralization and the collagen
      stiffness dominate fibril-array elasticity. Interestingly, the stiffness of the
      extra-fibrillar matrix has a strong influence on transverse and shear moduli of
      the fibril-array. The axial strain of the intra-fibrillar mineral platelets is 30
      90% of the applied fibril strain, depending on mineralization and collagen
      stiffness. The fibril-to-fibril-array strain ratio is essentially ~1. This study
      provides an improved insight in the parameters, which govern the fibril-array
      stiffness of mineralized tissues such as bone.

PMID- 20135191
TI  - 100 years since the discovery of non-Mendelian plastid phenotypes.

PMID- 20135192
TI  - Impacts of Batrachochytrium dendrobatidis infection on tadpole foraging
      performance.
AB  - Pathogen-induced modifications in host behavior, including alterations in
      foraging behavior or foraging efficiency, can compromise host fitness by reducing
      growth and development. Chytridiomycosis is an infectious disease of amphibians
      caused by the fungus Batrachochytrium dendrobatidis (Bd), and it has played an
      important role in the worldwide decline of amphibians. In larval anurans, Bd
      infections commonly result in reduced developmental rates, however, the
      mechanism(s) responsible are untested. We conducted laboratory experiments to
      test whether Bd infections reduced foraging performance of Grey Treefrog (Hyla
      chrysoscelis) and Fowler's Toad (Anaxyrus [= Bufo] fowleri) tadpoles. In the
      first experiment, we observed foraging behavior of Bd-infected and uninfected
      tadpoles to test for differences in foraging activity. In a second experiment, we
      tested for differences in the ingestion rates of tadpoles by examining the amount
      of food in their alimentary track after a 3-hour foraging period. We hypothesized
      that Bd-infected tadpoles would forage less often and less efficiently than
      uninfected tadpoles. As predicted, Bd-infected larvae forage less often and were
      less efficient at obtaining food than uninfected larvae. Our results show that Bd
      infections reduce foraging efficiency in Anaxyrus and Hyla tadpoles, and that Bd
      differentially affects foraging behavior in these species. Thus, our results
      provide a potential mechanism of decreased developmental rates of Bd-infected
      tadpoles.

PMID- 20135193
TI  - Chytrid blinders: what other disease risks to amphibians are we missing?
AB  - Amphibian declines are occurring on a global scale, and infectious disease has
      been implicated as a factor in some species. Batrachochytrium dendrobatidis (Bd)
      has been associated with amphibian declines and/or extinctions in many locations,
      however, few of the studies have actually performed detailed pathological
      investigations to link the emergence of the disease with mortality rates large
      enough to cause the declines. Many studies are based solely on the presence of
      infection, not disease, because of the reliance on molecular tests for Bd. The
      emphasis of the importance of Bd combined with easy molecular tests has resulted
      in poor investigations into amphibian mortality and declines in many areas. The
      line between infection and disease has been blurred, and a step back to basic
      pathological and biological investigations is needed as other disease risks to
      amphibians, such as ranaviruses, are likely being missed. In this article,
      starting points for proper investigative techniques for amphibian mortalities and
      declines are identified and areas that need to be improved, especially
      communication between biologist and veterinarians involved in amphibian disease
      research, are suggested. It is hoped that this will start a much needed
      discussion in the area and lead to some consensus building about methodologies
      used in amphibian disease research.

PMID- 20135194
TI  - Vorinostat enhances the cytotoxic effects of the topoisomerase I inhibitor SN38
      in glioblastoma cell lines.
AB  - Histone deacetylase (HDAC) inhibitors represent a promising class of anti-cancer
      agents that are actively being evaluated in the context of clinical trials in
      solid tumors, including glioblastoma. What makes these agents particularly
      attractive is their capacity to enhance the activity of commonly used cytotoxics
      in cancer therapy, including both chemotherapy and ionizing radiation. As recent
      investigations suggest HDAC inhibitors may potentiate the cytotoxicity of
      topoisomerase inhibitors, which continue to be a commonly used class of agents in
      the treatment of glioblastoma, we performed preclinical studies to determine if
      this combination may be a promising strategy in glioblastoma. The effects of the
      HDAC inhibitor vorinostat and SN38, which is the active metabolite of the
      topoisomerase I inhibitor CPT-11, was evaluated using the clonogenic assay.
      Various treatment schedules were tested to determine optimum drug sequencing.
      Induction of DNA double strand breaks (DSBs) with the combination of vorinostat
      and SN38 was evaluated using the neutral comet assay, and their subsequent repair
      was evaluated by gammaH2AX foci kinetics using immunofluorescent cytochemistry.
      Vorinostat enhanced the cytotoxicity of SN38 in glioblastoma cell lines. Optimal
      treatment schedules involved maximal concurrent administration of agents.
      Pretreatment with either agent did not enhance cytotoxicity. Vorinostat
      potentiated SN38-induced DNA DSBs and attenuated their subsequent repair. These
      results indicate vorinostat enhances the cytotoxicity of SN38 in glioblastoma
      cell lines, suggesting this combination may be a worthwhile strategy to test in
      the context of a clinical trial.

PMID- 20135195
TI  - Patterns of enrollment of infants with central nervous system tumours on
      cooperative group studies: a report from the Canadian Pediatric Brain Tumour
      Consortium.
AB  - In children under the age of 3, the most common solid tumours are brain tumors.
      Treatment for many of these patients includes surgery, chemotherapy and rarely
      radiation therapy. Many clinical trials have been performed in an attempt to
      establish the best treatment for these patients. Patients enrolled on clinical
      trials contribute to the establishment of the best therapy. We performed a
      national survey of all children less than the age of three with brain tumours and
      examined the contribution these patients made to clinical trials. A data bank was
      established using data collected from Canadian pediatric oncology centers on
      children less than age 3 diagnosed with brain tumours between 1990 and 2005. Data
      were collected on the use of adjunctive treatment after surgery, treatment on a
      protocol, reasons patients were not registered on a protocol, and reasons for
      discontinuation of therapy. From the 579 cases in the data bank, 302 (52%)
      patients were treated with further therapy after surgery. The use of further
      therapy after surgery was significantly higher in patients with cerebellar and
      brain stem tumors, patients who were over 1 year of age, patients with ependymal
      and embryonal tumors, and patients with high grade malignant tumors. Only 62
      (21%) patients were enrolled on a protocol for therapy. No factor was significant
      for being enrolled on a protocol. Reasons for not being registered on a protocol
      were mainly that there was no open COG/POG/CCG study or the study was not open at
      the institution. The therapy was stopped because of completion of the protocol in
      50% and because of disease progression in 34%. In Canada, about half of children
      under the age of 36 months with brain tumors are undergoing therapy following
      surgery for their malignancy but only a small fraction of them are enrolled on a
      clinical trial. There needs to be improved availability of clinical trials for
      these patients so that novel therapies can be evaluated and survival improved.

PMID- 20135196
TI  - Enhanced tolerance to freezing in tobacco and tomato overexpressing transcription
      factor TERF2/LeERF2 is modulated by ethylene biosynthesis.
AB  - Increasing numbers of investigations indicate that ethylene response factor (ERF)
      proteins play important roles in plant stress responses via interacting with GCC
      box and/dehydration-responsive element/C-repeat to modulate expression of
      downstream genes, but the detailed regulatory mechanism is not well elucidated.
      Revealing the modulation pathway of ERF proteins in response to stresses is
      vital. Previously, we showed that tomato ERF protein TERF2/LeERF2 is ethylene
      inducible, and ethylene production is suppressed in antisense TERF2/LeERF2
      tomatoes, suggesting that TERF2/LeERF2 functions as a positive regulator in
      ethylene biosynthesis. In this paper, we report that regulation of TERF2/LeERF2
      in ethylene biosynthesis is associated with enhanced freezing tolerance of
      tobacco and tomato. Analysis of gene expression showed that cold slowly induces
      expression of TERF2/LeERF2 in tomato, implying that TERF2/LeERF2 may be involved
      in cold response through ethylene modulation. To test the hypothesis, we first
      observed that overexpressing TERF2/LeERF2 tobaccos not only enhances freezing
      tolerance via activating expression of cold-related genes, but also significantly
      reduces electrolyte leakage. In addition, with treatment of ethylene biosynthesis
      inhibitor or ethylene receptor antagonist, we then showed that blockage of
      ethylene biosynthesis or the ethylene signaling pathway decreases freezing
      tolerance of overexpressing TERF2/LeERF2 tobaccos. Moreover, the results from
      tomatoes showed that overexpressing TERF2/LeERF2 tomatoes enhances while
      antisense TERF2/LeERF2 transgenic lines decreases freezing tolerance, and
      application of ethylene precursor 1-aminocyclopropane-1-carboxylic acid restored
      freezing tolerance of antisense lines. Therefore our results establish that
      TERF2/LeERF2 enhances freezing tolerance of plants through ethylene biosynthesis
      and the ethylene signaling pathway.

PMID- 20135197
TI  - The sprout inhibitors chlorpropham and 1,4-dimethylnaphthalene elicit different
      transcriptional profiles and do not suppress growth through a prolongation of the
      dormant state.
AB  - Chlorpropham (CIPC) and 1,4-dimethylnapthalene (DMN) are used to control
      postharvest sprouting of potato tubers. CIPC alters microtubule structure and
      function resulting in inhibition of cell division. The mechanism of action of DMN
      is unknown but, because it is a natural product found in potato tubers, there is
      speculation that it inhibits sprout growth by prolonging the dormant state. To
      address this issue, the effects of CIPC and DMN on abscisic acid (ABA) content
      and gene expression in potato tuber meristems were determined and compared to
      those found in dormant and non-dormant meristems. Dormancy progression was
      accompanied by a dramatic decline in ABA content and the ABA levels in meristems
      isolated from CIPC- and DMN- treated tubers were identical to the levels found in
      nondormant meristems demonstrating that sprout repression is not a function of
      elevated ABA. Evaluation of transcriptional profiles using cDNA microarrays
      demonstrated that there were similarities between CIPC- and DMN- treated tuber
      tissues particularly in transcripts that encode phosphatases and proteins
      associated with oxygen-related metabolism. Despite these similarities, there were
      significant differences in transcript profiles derived from treatment with either
      CIPC or DMN and the dormant state. These results suggested the mechanisms-of 
      action of DMN and CIPC are distinct and not due to a prolongation of the normal
      dormant condition.

PMID- 20135198
TI  - DNA methylation markers in colorectal cancer.
AB  - Colorectal cancer (CRC) arises as a consequence of the accumulation of genetic
      and epigenetic alterations in colonic epithelial cells during neoplastic
      transformation. Epigenetic modifications, particularly DNA methylation in
      selected gene promoters, are recognized as common molecular alterations in human
      tumors. Substantial efforts have been made to determine the cause and role of
      aberrant DNA methylation ("epigenomic instability") in colon carcinogenesis. In
      the colon, aberrant DNA methylation arises in tumor-adjacent, normal-appearing
      mucosa. Aberrant methylation also contributes to later stages of colon
      carcinogenesis through simultaneous methylation in key specific genes that alter
      specific oncogenic pathways. Hypermethylation of several gene clusters has been
      termed CpG island methylator phenotype and appears to define a subgroup of colon
      cancer distinctly characterized by pathological, clinical, and molecular
      features. DNA methylation of multiple promoters may serve as a biomarker for
      early detection in stool and blood DNA and as a tool for monitoring patients with
      CRC. DNA methylation patterns may also be predictors of metastatic or aggressive
      CRC. Therefore, the aim of this review is to understand DNA methylation as a
      driving force in colorectal neoplasia and its emerging value as a molecular
      marker in the clinic.

PMID- 20135199
TI  - EGFR mutations and the terminal respiratory unit.
AB  - Considerable knowledge has accumulated about mutations of the epidermal growth
      factor receptor (EGFR)-tyrosine kinase domain since these were first identified
      in 2004. Patients with nonsmall cell lung cancer with this mutation show dramatic
      clinical responses to treatment with EGFR-tyrosine kinase inhibitors, whose
      effectiveness has been established recently in large clinical trials. Most of the
      mechanisms responsible for resistance to treatment, which most responders
      experience eventually, have been elucidated, and methods to overcome resistance
      have been developed. In addition to the clinical benefit, understanding EGFR
      mutations sheds new light on the molecular and pathological aspects of this
      adenocarcinoma subset, which include frequent development in nonsmokers or
      females, and particular clusters within the molecular classification in lung
      cancer. In contrast to the involvement of EGFR mutations in the early stage of
      lung adenocarcinoma development, EGFR amplification is superimposed on the
      progression to invasive cancer. In this review, I summarize the
      clinicopathological characteristics of EGFR mutations in lung cancer. I also
      provide an overview of the current understanding of the lung adenocarcinoma
      subset harboring EGFR mutations with special reference to the molecular
      classification of lung cancer and the novel concept of the "terminal respiratory
      unit."

PMID- 20135200
TI  - GST profile expression study in some selected plants: in silico approach.
AB  - Glutathione acts as a protein disulphide reductant, which detoxifies herbicides
      by conjugation, either spontaneously or by the activity of one of a number of
      glutathione-S-transferases (GSTs), and regulates gene expression in response to
      environmental stress and pathogen attack. GSTs play roles in both normal cellular
      metabolisms as well as in the detoxification of a wide variety of xenobiotic
      compounds, and they have been intensively studied with regard to herbicide
      detoxification in plants. A newly discovered plant GST subclass has been
      implicated in numerous stress responses, including those arising from pathogen
      attack, oxidative stress and heavy-metal toxicity. In addition, plants GSTs play
      a role in the cellular response to auxins and during the normal metabolism of
      plant secondary products like anthocyanins and cinnamic acid. The present work
      involves two in silico analytical approaches-general secondary structure
      prediction studies of the proteins and detailed signature pattern studies of some
      selected GST classes in Arabdiopsis thaliana, mustard, maize and bread wheat by
      standard Bioinformatics tools; structure prediction tools; signature pattern
      tools; and the evolutionary trends were analyzed by ClustalW. For this purpose,
      sequences were obtained from standard databases. The work reveals that these
      proteins are mainly alpha helical in nature with specific signature pattern
      similar to phosphokinase C, tyrosine kinase and casein kinase II proteins, which
      are closely related to plant oxidative stress. This study aims to comprehend the
      relationship of GST gene family and plant oxidative stress with respect to
      certain specific conserved motifs, which may help in future studies for screening
      of biomodulators involved in plant stress metabolism.

PMID- 20135201
TI  - Tissue engineering approach to repair abdominal wall defects using cell-seeded
      bovine tunica vaginalis in a rabbit model.
AB  - The aim of this study was to engineer skeletal muscle tissue for repair abdominal
      wall defects. Myoblast were seeded onto the scaffolds and cultivated in vitro for
      5 days. Full thickness abdominal wall defects (3 x 4 cm) were created in 18 male
      New Zealand white rabbits and randomly divided into two equal groups. The defects
      of the first group were repaired with myoblast-seeded-bovine tunica vaginalis
      whereas the second group repaired with non-seeded-bovine tunica vaginalis and
      function as a control. Three animals were sacrificed at 7th, 14th, and 30th days
      of post-implantation from each group and the explanted specimens were subjected
      to macroscopic and microscopic analysis. In every case, seeded scaffolds have
      better deposition of newly formed collagen with neo-vascularisation than control
      group. Interestingly, multinucleated myotubes and myofibers were only detected in
      cell-seeded group. This study demonstrated that myoblast-seeded-bovine tunica
      vaginalis can be used as an effective scaffold to repair severe and large
      abdominal wall defects with regeneration of skeletal muscle tissue.

PMID- 20135202
TI  - Novel electrospun polyurethane/gelatin composite meshes for vascular grafts.
AB  - Novel polymeric micro-nanostructure meshes as blood vessels substitute have been
      developed and investigated as a potential solution to the lack of functional
      synthetic small diameter vascular prosthesis. A commercial elastomeric
      polyurethane (Tecoflex EG-80A) and a natural biopolymer (gelatin) were
      successfully co-electrospun from different spinnerets on a rotating mandrel to
      obtain composite meshes benefiting from the mechanical characteristics of the
      polyurethane and the natural biopolymer cytocompatibility. Morphological analysis
      showed a uniform integration of micrometric (Tecoflex) and nanometric (gelatin)
      fibers. Exposure of the composite meshes to vapors of aqueous glutaraldehyde
      solution was carried out, to stabilize the gelatin fibers in an aqueous
      environment. Uniaxial tensile testing in wet conditions demonstrated that the
      analyzed Tecoflex-Gelatin specimens possessed higher extensibility and lower
      elastic modulus than conventional synthetic grafts, providing a closer matching
      to native vessels. Biological evaluation highlighted that, as compared with
      meshes spun from Tecoflex alone, the electrospun composite constructs enhanced
      endothelial cells adhesion and proliferation, both in terms of cell number and
      morphology. Results suggest that composite Tecoflex-Gelatin meshes could be
      promising alternatives to conventional vascular grafts, deserving of further
      studies on both their mechanical behaviour and smooth muscle cell compatibility.

PMID- 20135203
TI  - The characteristics and transfection efficiency of PEI modified by biodegradable
      poly(beta-amino ester).
AB  - To improve the cytotoxicity of PEI25k and the transfection efficiency of
      poly(beta-amino ester) with DNA, we synthesized a poly(beta-amino ester), PEDP,
      bearing ester linkages in the backbone and tertiary amines in the backbone and
      side chain and prepared a binary mixture, PEDP-PEI25k, using physical blending
      meyhod. Both poly(beta-amino ester) PEDP and binary mixture PEDP-PEI25k, readily
      self-assembled with plasmid DNA (pCMV-beta gal) in a HEPES buffer, were
      characterized by dynamic light scattering. The results reveal that PEDP-PEI25k
      was able to self-assemble plasmid DNA into PEDP-PEI25k/DNA nano-complexes small
      enough to enter a cell through endocytosis. Titration studies were performed to
      determine the buffering capacities of PEDP and PEDP-PEI25k. The COS-7 cell
      viabilities in the presence of PEDP and PEDP-PEI25k were studied. At low mass
      ratio of PEDP/PEI25k (1/1), it is found that the transfection curve of PEDP
      PEI25k/DNA bearing a maximum peak is similar to that of PEI25k/DNA. In addition,
      the PEDP-PEI25k/DNA complexes were able to transfect COS-7 cells in vitro with a
      high efficiency comparable to a well-known gene carrier PEI25k/DNA. The results
      indicate that binary mixture PEDP-PEI25k is an attractive cationic carrier for
      gene delivery and an interesting candidate for further study.

PMID- 20135204
TI  - Effect of povidone-iodine addition on the corrosion behavior of cp-Ti in normal
      saline.
AB  - The effect of various concentrations of povidone-iodine (PI) on the corrosion
      behavior of a commercially pure titanium alloy (Ti-1) has been investigated in
      normal saline solution to simulate the povidone-iodine addition in an oral
      environment. The open circuit potential, electrochemical impedance spectroscopy
      and potentiodynamic polarization measurements have been used to characterize the
      electrochemical phenomena occurring on the alloy surface. The open circuit
      potential values for Ti-1 in various concentrations of PI shift considerably
      towards noble direction as compared to pure normal saline. In the potentiodynamic
      polarization curve for Ti-1 in various solutions, the cathodic current density
      has increased for all concentrations of PI and the anodic current density has
      decreased. Only the 0.1% PI concentration is able to inhibit corrosion of Ti-1 in
      normal saline and the other higher concentrations studied, accelerate corrosion.
      The EIS data for Ti-1 in normal saline and in various concentrations of PI
      follows a one time constant circuit, suggesting the formation of a single passive
      film on Ti-1 which is not altered by the addition of PI to normal saline.

PMID- 20135205
TI  - Investigation on magnetically controlled delivery of doxorubicin from
      superparamagnetic nanocarriers of gelatin crosslinked with genipin.
AB  - Gelatin (Type B) nanoparticles were prepared by a single W/O emulsion technique
      and characterized by infrared (IR) spectra, transmission electron micrographs
      (TEM), surface potential measurements and magnetization studies. Whereas the IR
      spectra clearly confirmed the presence of gelatin, genipin and doxorubicin in the
      loaded nanoparticles, the transmission electron micrographs (TEM) image depicts
      smooth surface, spherical shape and non-uniform size of nanoparticles (up to 100
      nm). The prepared nanoparticles were loaded with doxorubicin, a well known
      anticancer drug, and in vitro release dynamics of entrapped drug was investigated
      as a function of various experimental factors such as percent loading of the
      drug, chemical architecture of the nanocarriers, and pH, temperature, ionic
      strength and nature of the release medium in presence and absence of magnetic
      field. The nanoparticles were also studied for their water sorption capacity. The
      drug release process was analyzed kinetically using Ficks power law and a
      correlation was established between the quantity of released drug and swelling of
      the nanoparticles.

PMID- 20135206
TI  - Silk fibroin/chitosan-hyaluronic acid versus silk fibroin scaffolds for tissue
      engineering: promoting cell proliferations in vitro.
AB  - The feasibility of silk fibroin protein (SF) scaffolds for tissue engineering
      applications to promote cell proliferation has been demonstrated, as well as the
      ability to mimic natural extra-cellular matrix (ECM), SF/chitosan (CS), a
      polysaccharide, scaffolds for tissue engineering. However, the response of cells
      to SF/CS-hyaluronic acid (SF/CS-HA) scaffolds has not been examined, which this
      study attempts to do and then compares those results with those of SF scaffolds.
      SF/CS-HA microparticles were fabricated to produce scaffolds in order to examine
      the proliferations of human dermal fibroblasts (HDF) in the scaffolds. Positive
      zeta potentials and ATR-FTIR spectra confirmed the co-existence of SF and CS-HA
      in SF/CS-HA microparticles. HDF proliferated well and migrated into SF/CS-HA
      scaffolds for around 160 mum in depth, as well as those in SF scaffolds after 7
      days of cultivation, as observed using confocal microscopy. Interestingly, HDF
      grown in SF/CS-HA scaffolds had a markedly higher cell density than that in SF
      ones. Additionally, MTT assay revealed that the growth rates of HDF in SF/CS-HA
      scaffolds significantly exceeded (P < 0.01, n = 5) those in scaffolds of SF and
      SF/CS. The daily glucose consumptions and lactate formations, metabolic
      parameters, of HDF grown in SF/CS-HA and SF/CS scaffolds were significantly
      higher (P < 0.01, n = 3) than those in SF ones in most culturing days. Results of
      this study suggest that SF/CS-HA scaffolds have better cell responses for tissue
      engineering applications than SF ones.

PMID- 20135207
TI  - Model analysis of the concentration-dependent permeability of P-gp substrates.
AB  - PURPOSE: Recently, it was reported that the apparent Michaelis-Menten constant
      (Km(app)) of a P-glycoprotein (P-gp) substrate, defined for the extracellular
      substrate concentration, increases as the P-gp expression level in the cell
      increases. By its nature, the Km value should not depend on the level of P-gp
      expression. The purpose of this study is to establish a model which can estimate
      the Km value independent of the P-gp expression level in cells. METHODS: The
      previously reported concentration-dependent permeability of verapamil, quinidine,
      and vinblastine in MDR1-MDCKII, P-gp-highly induced Caco-2, P-gp-induced Caco-2,
      normal Caco-2, and MDR1-knockdown Caco-2 cells data were analyzed using a model
      in which the Km value was defined for the intracellular substrate concentration.
      RESULTS: The estimated Km values defined for the substrate concentration inside
      the cells were almost the same among various cells with different levels of P-gp
      expression. The estimated Vmax values were approximately proportional to the P-gp
      expression level. CONCLUSION: The established kinetic model was found to be
      rational based on the results that the Km values of P-gp substrates were about
      the same for cells expressing various levels of P-gp, while the Vmax values were
      proportional to the expression levels of P-gp.

PMID- 20135208
TI  - What made a successful hepatitis B program for reducing liver cancer disparities:
      an examination of baseline characteristics and educational intervention,
      infection status, and missing responses of at-risk Asian Americans.
AB  - Asian Americans, compared with other racial/ethnic groups, are disproportionately
      affected by Hepatitis B disease. The literature suggests that knowledge and
      awareness of prevention strategies such as receiving hepatitis B screening and
      vaccination are potential factors associated with occurrence of hepatitis B and
      liver cancer, while it is unclear how baseline characteristics relate to these
      effective hepatitis B prevention strategies. In the study, five Asian-American
      groups in the state of Maryland completed self-administered pre- and post-test
      after receiving lectures on hepatitis B prevention, and participated in blood
      screening for Hepatitis B. T-test and one-way ANOVA were used to explore the
      differences of baseline characteristics among these participants. Logistic
      regression was employed to study the baseline factors and association with
      completion of tests. All groups were significantly different in socioeconomic
      characteristics except for gender and immunization status, and only marginally
      different in infection status (P = 0.089). The mean pre- and post-test scores
      were different by group (P < 0.01). All groups had significantly improved
      knowledge of prevention (F = 7.65, P < 0.01). Age and race were positively
      related to immunization status, with older participants are more likely to get
      vaccinated (OR = 1.02, CI = 1.00-1.03). Chinese, Korean and Vietnamese were more
      likely to receive vaccination. For infection, only gender was correlated with
      infection status, with odds of being HBV carriers for females being 74% less than
      that for males (OR = 0.26, CI = 0.07-0.90). Participants who had only high school
      or lower education, retired, self-employed, higher income level, and married were
      less likely to complete surveys. The study found correlations of gender,
      infection status, age and race with immunization status. Males are more likely to
      be HBV carriers. It reveals new findings on the relationship between baseline
      characteristics and the completion of pre- and post-tests and missing responses.
      The information may provide potential directions for improve preventive program
      for at-risk communities.

PMID- 20135209
TI  - Women's knowledge of HPV and their perceptions of physician educational efforts
      regarding HPV and cervical cancer.
AB  - Human papillomavirus (HPV) was one of the most common sexually transmitted
      infections in women of child-bearing age in the US. It was estimated that nearly
      three out of every four American women between the ages of 15 and 49 would be
      infected with genital HPV over the course of their lifetime. Human papillomavirus
      was present in almost 100% of cervical cancers. Despite this growing epidemic,
      there was little knowledge and awareness of HPV among the general public. HPV was
      most often detected in abnormal Pap test results. However, women undergoing Pap
      tests lacked basic knowledge about HPV testing, abnormal results, and follow-up
      procedures. The purpose of this study was to determine women's knowledge of HPV
      and their perceptions of the education they received from their physician
      regarding the reason for a Pap test, explanation of Pap test results, and how
      effectively the physician explained associations between HPV and cell
      abnormalities, cervical cancer, risk factors, and preventive measures. A survey
      containing 33 questions was completed by 109 primarily professional women. Based
      on the data collected in this study it seems that physicians were not routinely
      providing HPV information to their female patients. Women reported their
      physicians were not educating them on testing for HPV and cervical cancer, risk
      factors associated with contracting HPV, and preventive measures associated with
      HPV. Younger physicians were more likely to discuss these topics with women than
      older physicians. Single women also reported more discussion with their physician
      on these topics than married women.

PMID- 20135210
TI  - Community norms, enforcement of minimum legal drinking age laws, personal beliefs
      and underage drinking: an explanatory model.
AB  - Strategies to enforce underage drinking laws are aimed at reducing youth access
      to alcohol from commercial and social sources and deterring its possession and
      use. However, little is known about the processes through which enforcement
      strategies may affect underage drinking. The purpose of the current study is to
      present and test a conceptual model that specifies possible direct and indirect
      relationships among adolescents' perception of community alcohol norms,
      enforcement of underage drinking laws, personal beliefs (perceived parental
      disapproval of alcohol use, perceived alcohol availability, perceived drinking by
      peers, perceived harm and personal disapproval of alcohol use), and their past-30
      day alcohol use. This study used data from 17,830 middle and high school students
      who participated in the 2007 Oregon Health Teens Survey. Structural equations
      modeling indicated that perceived community disapproval of adolescents' alcohol
      use was directly and positively related to perceived local police enforcement of
      underage drinking laws. In addition, adolescents' personal beliefs appeared to
      mediate the relationship between perceived enforcement of underage drinking laws
      and past-30-day alcohol use. Enforcement of underage drinking laws appeared to
      partially mediate the relationship between perceived community disapproval and
      personal beliefs related to alcohol use. Results of this study suggests that
      environmental prevention efforts to reduce underage drinking should target
      adults' attitudes and community norms about underage drinking as well as the
      beliefs of youth themselves.

PMID- 20135211
TI  - Genetic counseling for fetal abnormalities in a South African community.
AB  - Fetal abnormalities are congenital abnormalities identified prenatally. Women who
      have a fetal abnormality detected often have to make difficult decisions
      regarding continuation or termination of the pregnancy. The aims of this research
      project were: to investigate some of the factors that influenced the decision to
      terminate a pregnancy in which fetal abnormalities were diagnosed; and to
      determine the implications for genetic counseling practice in South Africa. The
      study was retrospective and file-based. A total of 171 women counseled for fetal
      abnormalities, between 2002 and 2006, were identified and relevant data were
      collected from their records. Altogether 116/170 (68.2%) women were offered
      termination of pregnancy, and 73/113 (65%) requested the procedure. Early
      gestation, gestation at the time termination was offered, and ethnicity of the
      patient, were significantly associated with a termination request. Black patients
      were less likely to request termination, but more likely to receive a late
      diagnosis than other patients. Genetic counselors need to adopt an advocacy and
      educational role to improve this situation. Furthermore, a better understanding
      of the cultural and ethnicity-related issues is required.

PMID- 20135212
TI  - A model of feedback control for the charge-balanced suppression of epileptic
      seizures.
AB  - Here we present several refinements to a model of feedback control for the
      suppression of epileptic seizures. We utilize a stochastic partial differential
      equation (SPDE) model of the human cortex. First, we verify the strong
      convergence of numerical solutions to this model, paying special attention to the
      sharp spatial changes that occur at electrode edges. This allows us to choose
      appropriate step sizes for our simulations; because the spatial step size must be
      small relative to the size of an electrode in order to resolve its electrical
      behavior, we are able to include a more detailed electrode profile in the
      simulation. Then, based on evidence that the mean soma potential is not the
      variable most closely related to the measurement of a cortical surface electrode,
      we develop a new model for this. The model is based on the currents flowing in
      the cortex and is used for a simulation of feedback control. The simulation
      utilizes a new control algorithm incorporating the total integral of the applied
      electrical potential. Not only does this succeed in suppressing the seizure-like
      oscillations, but it guarantees that the applied signal will be charge-balanced
      and therefore unlikely to cause cortical damage.

PMID- 20135213
TI  - Synchrony with shunting inhibition in a feedforward inhibitory network.
AB  - Recent experiments have shown that GABA(A) receptor mediated inhibition in adult
      hippocampus is shunting rather than hyperpolarizing. Simulation studies of
      realistic interneuron networks with strong shunting inhibition have been
      demonstrated to exhibit robust gamma band (20-80 Hz) synchrony in the presence of
      heterogeneity in the intrinsic firing rates of individual neurons in the network.
      In order to begin to understand how shunting can contribute to network synchrony
      in the presence of heterogeneity, we develop a general theoretical framework
      using spike time response curves (STRC's) to study patterns of synchrony in a
      simple network of two unidirectionally coupled interneurons (UCI network)
      interacting through a shunting synapse in the presence of heterogeneity. We
      derive an approximate discrete map to analyze the dynamics of synchronous states
      in the UCI network by taking into account the nonlinear contributions of the
      higher order STRC terms. We show how the approximate discrete map can be used to
      successfully predict the domain of synchronous 1:1 phase locked state in the UCI
      network. The discrete map also allows us to determine the conditions under which
      the two interneurons can exhibit in-phase synchrony. We conclude by demonstrating
      how the information from the study of the discrete map for the dynamics of the
      UCI network can give us valuable insight into the degree of synchrony in a larger
      feed-forward network of heterogeneous interneurons.

PMID- 20135214
TI  - Efficacy of a single-session HIV prevention intervention for black women: a group
      randomized controlled trial.
AB  - SisterLove Inc., a community-based organization (CBO) in Atlanta, Georgia,
      evaluated the efficacy of its highly interactive, single-session HIV prevention
      intervention for black women, the Healthy Love Workshop (HLW). HLW is delivered
      to pre-existing groups of women (e.g., friends, sororities) in settings of their
      choosing. Eligible groups of women were randomly assigned to receive the
      intervention (15 groups; 161 women) or a comparison workshop (15 groups; 152
      women). Behavioral assessments were conducted at baseline and at 3- and 6-month
      follow-ups. Among sexually active women at the 3-month follow-up, HLW
      participants were more likely than comparison participants to report having used
      condoms during vaginal sex with any male partner or with a primary male partner,
      and to have used condoms at last vaginal, anal or oral sex with any male partner.
      At the 6-month follow-up, HLW participants were more likely to report condom use
      at last vaginal, anal or oral sex with any male partner, and having an HIV test
      and receiving their test results. The study findings suggest that a single
      session intervention delivered to pre-existing groups of black women is an
      efficacious approach to HIV prevention. This study also demonstrates that a CBO
      can develop and deliver a culturally appropriate, effective HIV prevention
      intervention for the population it serves and, with adequate resources and
      technical assistance, rigorously evaluate its intervention.

PMID- 20135215
TI  - Intra-individual variation in serum C-reactive protein over 4 years: an
      implication for epidemiologic studies.
AB  - BACKGROUND: Data on long-term intra-individual variability in high-sensitivity C
      reactive protein (hsCRP) are needed to determine whether one measurement
      adequately reflects usual levels in prospective studies of on the etiology of
      cancer and other chronic diseases; when not reflective, the ability to
      statistically detect modest to moderate associations is reduced. The authors
      estimated the size of this source of variability and consequent attenuation of
      the relative risk (RR). METHODS: High-sensitivity C-reactive protein (hsCRP)
      concentration was measured using a high-sensitivity immunoturbidometric assay in
      sera collected at years 2, 4, and 6 from 50 men in the placebo arm of the
      Prostate Cancer Prevention Trial (PCPT). After natural logarithm-transformation
      of hsCRP, analysis of variance was used to estimate the within- and between
      individual variances from which the intra-class correlation coefficient (ICC) was
      calculated. RESULTS: The observed RR due to an ICC < 1 was calculated by e((ln
      true RR*ICC)) for a range of true RRs. The 4-year ICC was 0.66. Measuring hsCRP
      once and assuming no other error, if the true RRs were 1.50, 2.00, and 3.00 when
      comparing high with low concentration, then the observed RRs would be 1.31, 1.58,
      and 2.06, respectively. CONCLUSION: Investigators planning to measure hsCRP only
      once should design adequately sized studies to preserve inferences for
      hypothesized modest to moderate RRs.

PMID- 20135216
TI  - Characterization of soil heavy metal contamination and potential health risk in
      metropolitan region of northern China.
AB  - Soil in metropolitan region suffers great contamination risk due to the rapid
      urbanization especially in developing countries. Beijing and Tianjin, together
      with their surrounding regions, form a mega-metropolitan region in northern
      China. To assess the soil environmental quality, a total of 458 surface soil
      samples were collected from this area. Concentrations of Cr, Cu, Pb, Zn, As, Cd,
      and Hg were analyzed and compared to the Chinese environmental quality standards
      for soil. Multivariate analysis was carried out to identify the possible sources
      and Geographic Information Systems techniques were applied to visualize the
      spatial data. It was found that the primary inputs of As were due to pedogenic
      sources, whereas Hg was mainly of anthropogenic source. Other elements including
      Cr, Cu, Pb, Zn, and Cd were from both lithogenic and anthropogenic origins.
      Health risk assessment based on the maximum heavy metal concentration indicated
      that As derived from sewage irrigation area can result in carcinogenic lifetime
      risk due to ingestion and/or dermal contact of soil. The potential non
      carcinogenic risk for children is significant for Pb and the cumulative effect of
      multiple metals is of concern for children in the vicinity of mining site. The
      results increased our knowledge for understanding natural and anthropogenic
      sources as well as health risk for metals in metropolitan soil.

PMID- 20135217
TI  - Application of cooperative and non-cooperative games in large-scale water
      quantity and quality management: a case study.
AB  - In this paper, two cooperative and non-cooperative methodologies are developed
      for a large-scale water allocation problem in Southern Iran. The water shares of
      the water users and their net benefits are determined using optimization models
      having economic objectives with respect to the physical and environmental
      constraints of the system. The results of the two methodologies are compared
      based on the total obtained economic benefit, and the role of cooperation in
      utilizing a shared water resource is demonstrated. In both cases, the water
      quality in rivers satisfies the standards. Comparing the results of the two
      mentioned approaches shows the importance of acting cooperatively to achieve
      maximum revenue in utilizing a surface water resource while the river water
      quantity and quality issues are addressed.

PMID- 20135218
TI  - Mercury concentrations in tidal marsh sparrows and their use as bioindicators in
      Delaware Bay, USA.
AB  - Mercury (Hg) contamination from industrial sources is pervasive throughout North
      America and is recognized by the US Environmental Protection Agency as a health
      hazard for wildlife and humans. Avian species are commonly used as bioindicators
      of Hg because they are sensitive to contaminants in the environment and are
      relatively easy to sample. However, it is important to select the appropriate
      avian species to use as a bioindicator, which should be directly related to the
      project objectives. In this study, we tested the utility of two tidal marsh
      sparrows, Seaside (Ammodramus maritimus) and Saltmarsh (Ammodramus caudacutus)
      sparrows, as bioindicator species of the extent of Hg contamination in tidal
      marshes along the Delaware Bay. To determine the possibility of using one or both
      of these species, we estimated sparrow blood Hg burden in five Delaware
      watersheds. We found no difference in Hg concentrations between species (F
      (1,133) < 0.01, P=0.99), but Saltmarsh Sparrows had limited sample size from each
      site and were, therefore, not appropriate for a Delaware Bay-wide Hg indicator.
      Seaside Sparrows, however, were abundant and relatively easy to sample in the
      five watersheds. Seaside Sparrow blood Hg levels ranged from 0.15 to 2.12 ppm,
      differed among drainages, and were greatest in two drainages distant from the
      Delaware Bay shoreline (F (4,95) =2.51, P=0.05). Based on a power analysis for
      Seaside Sparrow blood Hg, we estimated that 16 samples would be necessary to
      detect differences among sites. Based on these data, we propose that Seaside
      Sparrows may be used as a tidal marsh Hg bioindicator species given their habitat
      specificity, relative abundance, widespread distribution in marsh habitats, ease
      of sampling, and limited variation in blood Hg estimates within a sampling area.
      In Delaware Bay, Saltmarsh Sparrows may be too rare (making them difficult to
      sample) to be a viable tidal marsh Hg bioindicator.

PMID- 20135219
TI  - Heavy metal content in the femora of yellow-necked mouse (Apodemus flavicollis)
      and wood mouse (Apodemus sylvaticus) from different types of polluted environment
      in Slovakia.
AB  - Heavy metal content in the femora of yellow-necked mouse (Apodemus flavicollis)
      and wood mouse (Apodemus sylvaticus) caught in different polluted biotopes of a
      low hill level in Slovakia (Novaky and Kolinany) was investigated in the present
      study. Length, weight and histological structure of mouse bones have also been
      analysed. According to our results, higher concentrations of Cd, Ni, Fe, Cu and
      Zn were detected in the femora of A. flavicollis from Kolinany area. Similarly,
      we observed higher concentrations of Ni, Fe, Cu and Zn in the bones of A.
      sylvaticus trapped at the same biotope. Significant differences were observed for
      concentrations of Ni and Zn in both species (P<0.05). The measured values for
      bone length and bone weight were higher in yellow-necked mice and wood mice from
      Novaky locality (P<0.01). Histological observation of thin sections from femora
      of A. flavicollis and A. sylvaticus revealed an outer and inner non-vascular
      lamellar layer around a poorly developed reticular layer. We did not identify
      demonstrable changes in qualitative histological characteristics of the femora
      between the mice (A. flavicollis and A. sylvaticus separately) from different
      types of polluted environment. Also, no statistically significant differences for
      all the measured variables of primary osteons' vascular canals were observed.
      Correlation analysis in yellow-necked mouse showed high positive relation between
      bone weight and bone length (r=0.66), area and perimeter (r=0.87) and perimeter
      and maximum diameter (r=0.87). In wood mouse, high positive correlation between
      bone weight and bone length (r=0.80), area and perimeter (r=0.72), area and
      maximum diameter (r=0.66) and perimeter and maximum diameter (r=0.74) was found.
      Our results demonstrate slightly elevated accumulation of some heavy metals in
      the femora of yellow-necked mouse and wood mouse from Kolinany biotope and thus
      give an evidence of a contamination of the environment.

PMID- 20135220
TI  - Developing brain as an endocrine organ: a paradoxical reality.
AB  - The maintaining of homeostasis in the organism in response to a variable
      environment is provided by the highly hierarchic neuroendocrine-immune system.
      The crucial component of this system is the hypothalamus providing the endocrine
      regulation of key peripheral organs, and the adenohypophysis. In this case,
      neuron-derived signaling molecules (SM) are delivered to the blood vessels in
      hypothalamic "neurohaemal organs" lacking the blood-brain barrier (BBB), the
      posterior lobe of the pituitary and the median eminence. The release of SM to the
      blood vessels in most other brain regions is prohibited by BBB. According to the
      conventional concept, the development of the neuroendocrine system in ontogenesis
      begins with the "maturation" of peripheral endocrine glands which first are self
      governed and then operate under the adenohypophysial control. Meantime, the brain
      maturation is under the control of SM secreted by endocrine glands of the
      developing organism and coming from the placenta and maternal organism. The
      hypothalamus is involved in the neuroendocrine regulation only after its full
      maturation that is followed by the conversion of the opened-looped neuroendocrine
      system to the closed-looped system as in adulthood. Neurons of the developing
      brain begin to secrete SM shortly after their origin and long before the
      establishment of specific interneuronal relations providing initially autocrine
      and paracrine morphogenetic influence on differentiating target neurons. Taking
      into account that the brain lacks BBB over this ontogenetic period, we
      hypothesized that it operates as the multipotent endocrine gland secreting SM to
      the general circulation and thereby providing the endocrine regulation of
      peripheral organs and the brain. The term "multipotent" means that the spectrum
      of the brain-derived circulating SM and their occupancy at the periphery in the
      developing organism should greatly exceed those in adulthood. In order to test
      this hypothesis, gonadotropin-releasing hormone (GnRH), dopamine (DA), and
      serotonin (5-hydroxytryptamine, 5-HT) were chosen as the markers of the
      presumptive endocrine function of the brain in ontogenesis. According to our
      data, the concentrations of GnRH, DA, and 5-HT in the rat general circulation
      during the perinatal period, i.e. before the establishment of BBB, was as high as
      those in the portal circulation in adulthood. The concentrations of circulating
      GnRH and DA dropped to almost undetectable level after the development of BBB
      suggesting their brain origin. This suggestion has been proven by showing an
      essential decrease of GnRH, DA, and 5-HT concentrations in general circulation of
      perinatal rats after microsurgical elimination of synthesizing neurons or the
      inhibition of specific syntheses in the brain before the establishment of BBB.
      GnRH, DA, and 5-HT apparently as dozens of other brain-derived SM appear to be
      capable of providing the endocrine influence on their peripheral targets like the
      adenohypophysis, gonads, kidney, heart, blood vessels, and the brain (endocrine
      autoregulation). Although the ontogenetic period of the brain operation as the
      multipotent endocrine gland is relatively short, the brain-derived SM are thought
      to be capable of providing long-lasting morphogenetic effects on peripheral
      targets and the brain. Thus, the developing brain operates as the multipotent
      endocrine gland from the onset of neurogenesis to the establishment of BBB
      providing the endocrine regulation of the developing organism.

PMID- 20135221
TI  - Computer-aided design and synthesis of tetra-aryl-substituted alkenes and their
      bioevaluation as a selective modulator of estrogen-related receptor gamma.
AB  - This study reports on a translational exercise in computer-aided rational drug
      design, chemical synthesis, and bioevaluation using a cell-based reporter gene
      assay, pursued exclusively for the development of specific estrogen-related
      receptor gamma (ERR gamma) inverse agonists with selectivity over estrogen
      receptor alpha (ER alpha). We designed and synthesized a 9-membered small
      molecule collection, which has, as the key molecular framework, tetra-aryl
      substituted alkene derived from 4-hydroxytamoxifen (4-OHT), a known ERR gamma
      inverse agonist and antagonist of ER alpha. Although we could not achieve a more
      potent inverse agonist than GSK5182 from our compound collection, we demonstrated
      a reasonable correlation between the in silico docking simulation and biological
      data of transcriptional regulation on nuclear receptors. Therefore, we suggest
      that structural information regarding proteins-of-interest provides a novel
      insight into the rational design of new therapeutic agents and that the
      utilization of docking simulation as a preliminary filtering tool might be a
      useful option for medicinal chemists or chemical biologists.

PMID- 20135222
TI  - Evaluating the fitness of human lysozyme transgenic dairy goats: growth and
      reproductive traits.
AB  - While there are many reports in the literature describing the attributes of
      specific applications of transgenic animals for agriculture, there are relatively
      few studies focusing on the fitness of the transgenic animals themselves. This
      work was designed to gather information on genetically modified food animals to
      determine if the presence of a transgene can impact general animal production
      traits. More specifically, we used a line of transgenic dairy goats expressing
      human lysozyme in their mammary gland to evaluate the reproductive fitness and
      growth and development of these animals compared to their non-transgenic
      counterparts and the impact of consuming a transgenic food product, lysozyme
      containing milk. In males, none of the parameters of semen quality, including
      semen volume and concentration, total sperm per ejaculate, sperm morphology,
      viability and motility, were significantly different between transgenic bucks and
      non-transgenic full-sib controls. Likewise, transgenic females of this line did
      not significantly differ in the reproductive traits of gestation length and
      litter size compared to their non-transgenic counterparts. To evaluate growth,
      transgenic and non-transgenic kid goats received colostrum and milk from either
      transgenic or non-transgenic does from birth until weaning. Neither the presence
      of the transgene nor the consumption of milk from transgenic animals
      significantly affected birth weight, weaning weight, overall gain and post-wean
      gain. These results indicate that the analyzed reproductive and growth traits
      were not regularly or substantially impacted by the presence or expression of the
      transgene. The evaluation of these general parameters is an important aspect of
      defining the safety of applying transgenic technology to animal agriculture.

PMID- 20135223
TI  - Effects of transgenic rootstocks on growth and development of non-transgenic
      scion cultivars in apple.
AB  - Although cultivation of genetic modified (GM) annual crops has been steadily
      increasing in the recent 10 years, the commercial cultivation of GM fruit tree is
      still very limited and reports of field trials on GM fruit trees are rare. This
      is probably because development and evaluation of GM fruit trees require a long
      period of time due to long life cycles of trees. In this study, we report results
      from a field trial on three rolB transgenic dwarfing apple rootstocks of M26 and
      M9 together with non-transgenic controls grafted with five non-transgenic scion
      cultivars. We intended to investigate the effects of transgenic rootstock on non
      transgenic scion cultivars under natural conditions as well as to evaluate the
      potential value of using the rolB gene to modify difficult-to-root rootstocks of
      fruit trees. The results showed that all rolB transgenic rootstocks significantly
      reduced vegetative growth including tree height regardless of scion cultivar,
      compared with the non-transgenic rootstocks. Flowering and fruiting were also
      decreased for cultivars grown on the transgenic rootstocks in most cases, but the
      fruit quality was not clearly affected by the transgenic rootstocks. Cutting
      experiment and RT-PCR analysis showed that the rolB gene was stably expressed
      under field conditions. PCR and RT-PCR analyses displayed that the rolB gene or
      its mRNA were not detectable in the scion cultivars, indicating no translocation
      of the transgene or its mRNA from rootstock to scion. Our results suggest that
      rolB modified rootstocks should be used in combination with vigorous scion
      cultivars in order to obtain sufficient vegetative growth and good yield.
      Alternatively, the rolB gene could be used to dwarf vigorous rootstocks of fruit
      trees or produce bonzai plants as it can significantly reduce the vegetative
      growth of plants.

PMID- 20135224
TI  - Human growth hormone expressed in tobacco cells as an arabinogalactan-protein
      fusion glycoprotein has a prolonged serum life.
AB  - Therapeutic proteins with molecular weights lower than 40 kDa often have short
      serum half-lives due to their susceptibility to serum proteases and rapid renal
      clearance. Chemical derivatization, such as PEGylation, or expression as serum
      albumin fusions increases molecular mass and overcome these problems but at the
      expense of decreased bioactivity. Here we applied a new method that yields
      biologically potent recombinant human growth hormone (rhGH) with increased serum
      half-life when expressed as an arabinogalactan-protein (AGP) in tobacco BY-2
      cells. Thus, rhGH was expressed with 10 repeats of the AGP glycomodule Ser-Hyp
      (SO) at the C-terminus (rhGH-(SO)(10)). We also expressed rhGH as an AGP-enhanced
      green fluorescent protein (EGFP) fusion, designated rhGH-(SO)(10)-EGFP, to assess
      the cellular distribution of the glycoprotein, which was mainly extracellular.
      Recombinant hGH-(SO)(10) bound the hGH receptor with an affinity similar to that
      of a rhGH standard, stimulated the same intracellular signaling pathway as hGH,
      but possessed an in vivo serum half-life more than sixfold that of the hGH
      control. Furthermore, rhGH-(SO)(10) gave a 500 fold greater secreted yield than
      the non-glycosylated control rhGH that was also targeted for secretion. Detailed
      analysis of the rhGH-(SO)(10) glycans indicated a conserved structure with
      relatively little microheterogeneity and an average size of 25 monosaccharide
      residues. These results were consistent with earlier work expressing interferon
      alpha 2b as an AGP chimera and further demonstrate the feasibility of this
      approach to the production of long-acting, biologically potent therapeutic
      proteins by plant cells.

PMID- 20135225
TI  - Strains nodulating Lupinus albus on different continents belong to several new
      chromosomal and symbiotic lineages within Bradyrhizobium.
AB  - In this work we analysed different chromosomal and symbiotic markers in rhizobial
      strains nodulating Lupinus albus (white lupin) in several continents.
      Collectively the analysis of their rrs and atpD genes, and 16S-23S intergenic
      spacers (ITS), showed that they belong to at least four chromosomal lineages
      within the genus Bradyrhizobium. Most isolates from the Canary Islands (near to
      the African continent) grouped with some strains isolated on mainland Spain and
      were identified as Bradyrhizobium canariense. These strains are divided into two
      ITS subgroups coincident with those previously described from isolates nodulating
      Ornithopus. The remaining strains isolated on mainland Spain grouped with most
      isolates from Chile (American continent) forming a new lineage related to
      Bradyrhizobium japonicum. The strains BLUT2 and ISLU207 isolated from the Canary
      Islands and Chile, respectively, formed two new lineages phylogenetically close
      to different species of Bradyrhizobium depending on the marker analyzed. The
      analysis of the nodC gene showed that all strains nodulating L. albus belong to
      the biovar genistearum; nevertheless they form four different nodC lineages of
      which lineage C is at present exclusively formed by L. albus endosymbionts
      isolated from different continents.

PMID- 20135226
TI  - Electronic communications with patients: improved safety, improved access, or
      electronic leash-principles and prospects.

PMID- 20135227
TI  - The yield of a continuously patent gastroesophageal junction during upper
      endoscopy as a predictor of esophagitis in children.
AB  - BACKGROUND AND AIMS: Over the last years we have noted an association between the
      endoscopic finding of a continuously patent gastroesophageal junction (GEJ)
      throughout the procedure and macroscopic or microscopic esophagitis. We could not
      find documentation for these endoscopic findings as a predictor of esophagitis in
      the literature. We aimed to find an association between these findings and
      microscopic and macroscopic esophagitis. METHODS: During upper endoscopy, we
      routinely observe the GEJ for about 60 s and note the behavior of the GEJ and
      esophageal contractions. Patients with a persistently patent GEJ were recorded. A
      group of patients referred for upper endoscopy for reasons other than suspected
      reflux, whose esophagus was normal, and patients with reflux symptoms served as a
      control groups. RESULTS: We found 21 patients (3.0%) in whom a patent GEJ had
      been noted. No significant age differences were noted between study and control
      groups. Eighteen out of 21 patients (86%) in the study group had varying degrees
      of microscopic esophagitis ranging from mild to severe (ten with mild
      esophagitis, three with moderate esophagitis, and five with severe esophagitis).
      Interestingly, ten out of 18 (55%) study patients with esophagitis on biopsies
      had no evidence of additional esophageal abnormality. Although all control
      patients had a normally appearing esophagus on upper endoscopy, 8/26 (31%) had
      mild esophagitis on biopsies. Differences were statistically significant (p <
      0.001). CONCLUSIONS: A continuously patent GEJ predicts quite accurately the
      presence of esophagitis in biopsies and may serve an additional endoscopic
      finding for the diagnosis of esophagitis especially non-erosive GER.

PMID- 20135228
TI  - Potential drug-drug interactions and radiodiagnostic procedures: an in-hospital
      survey.
AB  - OBJECTIVES: To evaluate the type, frequency, severity and predictors of potential
      Drug-Drug Interactions (DDIs) in a cohort of patients undergoing radiodiagnostic
      procedures. SETTING: Eight Radiology wards located in Tuscany (Italy). METHODS:
      All participants exposed to at least two medications were included in the
      analysis. DDIs were grouped according to their severity as 'minor', 'moderate' or
      'major'. A logistic model was used to estimate Odds Ratios and 95% Confidence
      Intervals for all predictors of potential DDI. MAIN OUTCOME MEASURES: Type and
      predictors of potential DDI in a cohort of patients undergoing radiodiagnostic
      procedures. RESULTS: One-thousand-and-two subjects (57.6% females; mean age: 67.3
      +/- 12.2) entered the analysis, and 46.1% of them incurred in a potential DDI
      (78.9% 'moderate' in severity). The combination of allopurinol and ACE-inhibitors
      was the most frequent (21/153) among major potential DDIs, while steroids were
      involved in all cases of potential DDI due to premedication. Co-morbidity, number
      of co-medications, advanced age and premedication use increased the risk of
      potential DDI; a protective role was found for positive history of allergy. When
      the analysis was restricted to subjects with premedication (n = 93), only 12.9%
      of them reported a potential DDI directly attributable to premedication drugs.
      CONCLUSIONS: Among patients undergoing radiological examination, types and
      predictors of potential DDIs appeared in agreement with other kind of in-hospital
      populations. Premedication revealed to be a proxy predictor for potential DDIs.
      Considering the poor capability of the prescriber in recognizing interactions,
      their systematic evaluation (using an informatics tool) in patients undergoing
      radiological examination might be helpful in preventing the occurrence of
      clinically relevant DDIs.

PMID- 20135229
TI  - Isoprene emission protects photosynthesis in sunfleck exposed Grey poplar.
AB  - In the present study, we combined transient temperature and light stress
      (sunfleck) and comparably analyzed photosynthetic gas exchange in Grey poplar
      which has been genetically modified in isoprene emission capacity. Overall, we
      demonstrate that for poplar leaves the ability to emit isoprene is crucial to
      maintain photosynthesis when exposed to sunflecks. Net CO2 assimilation and
      electron transport rates were strongly impaired in sunfleck-treated non-isoprene
      emitting poplars. Similar impairment was not detected when the leaves were
      exposed to high light (lightflecks) only. Within 10 h non-isoprene emitting
      poplars recovered from sunfleck-related impairment as indicated by chlorophyll
      fluorescence and microarray analysis. Unstressed leaves of non-isoprene emitting
      poplars had higher ascorbate contents, but also higher contents of
      malondialdehyde than wild-type. Microarray analyses revealed lipid and
      chlorophyll degradation processes in the non-isoprene emitting poplars. Thus,
      there is evidence for an adjustment of the antioxidative system in the non
      isoprene emitting poplars even under normal growth conditions.

PMID- 20135230
TI  - Community health development: a strategy for reinventing America's health care
      system one community at a time.
AB  - The purpose of this article is to propose a set of ideas for reinventing
      America's health care system, one community at a time. Community health
      development is proposed as a strategy and approach to population health
      improvement, the ultimate goal of health care reform. The practice of community
      health development, particularly the partnership approach, provides guidance
      about how this approach might be employed as a national health care reform
      strategy. Examples of two communities successfully using the partnership approach
      illustrate the methods described. Six specific recommendations for policy makers
      and public administrators in the new administration resulting from our experience
      with community health development are presented. First, adopt and apply community
      health development (CHD) as the American approach for facilitating population
      health improvement and building community capacity. Second, the partnership
      approach should be promoted as a model for communities to use in implementing
      CHD. Third, make the community-level the focus for planning, implementing,
      evaluating, and sustaining a full continuum of health and human services. Fourth,
      formally recognize the social determinants of health as a key component of a new
      population/community health status model and as a public policy driver for health
      care reform, marketplace issues, and population health status improvement at all
      levels of society. Fifth is a call for a national strategy for the recruitment,
      training, education, and support of individuals to facilitate this community
      movement. Sixth, Congress and the Obama Administration adopt and apply CHD as a
      national strategy and utilize American community-based experiences to bring about
      a national plan.

PMID- 20135231
TI  - An overview of a cohort of South African patients with mitochondrial disorders.
AB  - Mitochondrial disorders are frequently encountered inherited diseases
      characterized by unexplained multisystem involvement with a chronic,
      intermittent, or progressive nature. The objective of this paper is to describe
      the profile of patients with mitochondrial disorders in South Africa. Patients
      with possible mitochondrial disorders were accessed over 10 years. Analyses for
      respiratory chain and pyruvate dehydrogenase complex enzymes were performed on
      muscle. A diagnosis of a mitochondrial disorder was accepted only if an enzyme
      activity was deficient. Sixty-three patients were diagnosed with a mitochondrial
      disorder, including 40 African, 20 Caucasian, one mixed ancestry, and two Indian
      patients. The most important findings were the difference between African
      patients and other ethnicities: respiratory chain enzyme complexes CI+III or
      CII+III deficiencies were found in 52.5% of African patients, being of
      statistical significance (p value = 0.0061). They also presented predominantly
      with myopathy (p value = 0.0018); the male:female ratio was 1:1.2. Twenty-five
      (62.5%) African patients presented with varying degrees of a myopathy accompanied
      by a myopathic face, high palate, and scoliosis. Fourteen of these 25 also had
      ptosis and/or progressive external ophthalmoplegia. No patients of other
      ethnicities presented with this specific myopathic phenotype. Caucasian patients
      (16/20) presented predominantly with central nervous system involvement. Of the
      South African pediatric neurology patients, Africans are more likely to present
      with myopathy and CII+III deficiency, and Caucasian patients are more likely to
      present with encephalopathy or encephalomyopathy.

PMID- 20135233
TI  - Reflections on the development of health inequalities policy in England.
AB  - Abstracts are written to summarise documents and to whet the reader's interest.
      Alas, many readers just use them as a substitute for reading the whole paper,
      which given the brevity of abstracts can give a somewhat distorted impression. I
      hope that having read this abstract, you will read on. If you do, you will find
      that I offer a little personal history and a little impersonal history on the
      development of interest in the issue of health inequalities in England. I then
      summarise the policy response of recent Labour administrations, briefly detail
      the effects of this response, and finally offer my own three-pronged policy
      attack on our thus far really quite stubborn inequalities in health.

PMID- 20135232
TI  - A systemic proteomic analysis of Populus chloroplast by using shotgun method.
AB  - The chloroplast is one of the most important organelles in plants. Proteomic
      investigations of chloroplasts have been undertaken for many herb plant species,
      but to date no such investigation has been reported for woody plant chloroplasts.
      In the present study we initiated a systematic proteomic study of Populus
      chloroplasts using a shotgun proteomic method. After isolation of chloroplasts
      and tryptic digestion of the proteins, the protein fragments were separated via
      HPLC using an SCX column, and the peptides were analyzed by LC-MS/MS; 119
      proteins were successfully identified. Based on annotation information in the
      UniProtKB/Swiss-Prot database, these proteins were identified as being localized
      in the chloroplast thylakoid membrane, chloroplast stroma, chloroplast thylakoid
      lumen, and plastoglobules. Over 50% of all identified proteins were confirmed as
      chloroplast thylakoid proteins, and 85 are encoded by the chloroplast genome with
      the remaining proteins encoded by the nuclear genome. Based on functional
      annotation, these proteins were classified into four functional categories,
      including photosynthesis, redox regulation and stress, primary and secondary
      metabolism, transport and signaling. These data provide a valuable basis for
      further studies on photosynthesis in poplar species.

PMID- 20135234
TI  - Socio-demographic and clinical determinants of quality of life in Chinese
      patients with schizophrenia: a prospective study.
AB  - PURPOSE: The aim of the study was to assess the changes in the quality of life
      (QOL) of Chinese schizophrenia patients and to identify their predictors over a 1
      year follow-up. METHODS: A cohort of 116 schizophrenia patients was recruited,
      and their socio-demographic and clinical characteristics including psychotic and
      depressive symptoms, drug-induced side effects, social functioning, and QOL were
      assessed with standardized rating instruments. The patients received standard
      psychiatric care and were followed up for 1 year. RESULTS: The psychotic and
      depressive symptoms, extrapyramidal side effects, and QOL domains of physical
      functioning, role limitations due to physical problems, social functioning, and
      role limitations due to emotional problems all improved significantly. Social
      functioning was a predictor of baseline QOL and change at 1-year follow-up.
      CONCLUSIONS: Routine clinical management was effective in improving schizophrenia
      patients' psychopathology and several domains of QOL. QOL was related to the
      level of social functioning and had only a weak association with socio
      demographic factors.

PMID- 20135235
TI  - Coupling changes in cortical and pontine sigma and theta frequency oscillations
      following monoaminergic lesions in rat.
AB  - PURPOSE: Sigma and theta frequency electroencephalogram (EEG) oscillations
      exhibit substantial and well-recognized shifts with transitions across sleep and
      wake states. We aimed in this study to test the changes in coupling between these
      characteristic oscillations of non-rapid-eye-movement (NREM)/rapid-eye-movement
      (REM) sleep within and between cortical and pontine EEGs following monoaminergic
      lesion, by using the Pearson's product-moment correlation coefficients. METHODS:
      Experiments were performed in 14 adult, male Sprague Dawley rats chronically
      instrumented for sleep recording. We lesioned the dorsal raphe nucleus axon
      terminals in four rats using PCA neurotoxin (p-chloroamphetamine; Sigma-Aldrich,
      MO) administered as two intraperitoneal (IP) injections (6 mg/kg) 24 h apart.
      Lesioning of locus coeruleus axon terminals was performed in five rats using DSP
      4 neurotoxin (N-2-chloroethyl-N-ethyl-2-bromobenzilamine; Sigma-Aldrich, MO) in a
      single IP dose of 50 mg/kg. RESULTS & CONCLUSIONS: Our previous study [Saponjic
      et al., Physiol Behav 90:1-10, 2007] demonstrated that these systemically induced
      monoaminergic lesions failed to produce significant changes in sleep/wake
      distribution from control conditions. The present study, by using spectral
      analysis and by examining the Pearson's correlation coefficients and their
      approximate probability density (APD) distribution profiles in control and lesion
      condition, demonstrates significant augmentation of the sigma/theta coupling
      strength, an inversion of cortical sigma/theta coupling direction and emergence
      of an additional sigma/theta coupling "mode" specific to the post-lesion state
      only within the cortex. By using the Pearson's correlation coefficients and their
      APD profiles, instead of classical sleep/wake distribution analysis, as a measure
      of direction and strength of sigma/theta coupling within and between cortex and
      pons, we were able to uncover the impact of a tonically decreased level of brain
      monoamines as altered strength and mode of coupling between sigma and theta
      oscillations. Specifically, a new mode of sigma/theta coupling emerged following
      lesion, which was specific to NREM sleep, suggests that loss of monoaminergic
      signaling interferes with NREM sleep consolidation. Our results also indicate an
      importance of monoamines in control of the sleep spindle and theta rhythm
      generators.

PMID- 20135237
TI  - Mathematical modelling of the Aux/IAA negative feedback loop.
AB  - The hormone auxin is implicated in regulating a diverse range of developmental
      processes in plants. Auxin acts in part by inducing the Aux/IAA genes. The
      associated pathway comprises multiple negative feedback loops (whereby Aux/IAA
      proteins can repress Aux/IAA genes) that are disrupted by auxin mediating the
      turnover of Aux/IAA protein. In this paper, we develop a mathematical model of a
      single Aux/IAA negative feedback loop in a population of identical cells. The
      model has a single steady-state. We explore parameter space to uncover a number
      of dynamical regimes. In particular, we identify the ratio between the Aux/IAA
      protein and mRNA turnover rates as a key parameter in the model. When this ratio
      is sufficiently small, the system can evolve to a stable limit cycle,
      corresponding to an oscillation in Aux/IAA expression levels. Otherwise, the
      steady-state is either a stable-node or a stable-spiral. These observations may
      shed light on recent experimental results.

PMID- 20135238
TI  - Effects of demographic stochasticity on population persistence in advective
      media.
AB  - Many populations live and disperse in advective media. A fundamental question,
      known as the "drift paradox" in stream ecology, is how a closed population can
      survive when it is constantly being transported downstream by the flow. Recent
      population-level models have focused on the role of diffusive movement in
      balancing the effects of advection, predicting critical conditions for
      persistence. Here, we formulate an individual-based stochastic analog of the
      model described in (Lutscher et al., SIAM Rev. 47(4):749-772, 2005) to quantify
      the effects of demographic stochasticity on persistence. Population dynamics are
      modeled as a logistic growth process and dispersal as a position-jump process on
      a finite domain divided into patches. When there is no correlation in the
      interpatch movement of residents, stochasticity simply smooths the persistence
      extinction boundary. However, when individuals disperse in "packets" from one
      patch to another and the flow field is memoryless on the timescale of packet
      transport, the probability of persistence is greatly enhanced. The latter
      transport mechanism may be characteristic of larval dispersal in the coastal
      ocean or wind-dispersed seed pods.

PMID- 20135239
TI  - Laparoscopic cardiomyotomy for achalasia: clinical outcomes beyond 5 years.
AB  - BACKGROUND: Laparoscopic cardiomyotomy is the most common surgical procedure for
      the treatment of achalasia, although few reports describe long-term surgical
      outcomes. METHODS: The outcomes for 155 patients who underwent a laparoscopic
      cardiomyotomy with anterior partial fundoplication more than 5 years ago (July
      1992 to May 2004) were determined. Patients were followed prospectively at yearly
      time points using a structured questionnaire which evaluated symptoms of
      dysphagia, reflux, side-effects, and overall satisfaction with the clinical
      outcome. RESULTS: Clinical data were available for 125 patients. Thirteen
      patients died within 5 years of surgery, four were unable to complete the
      questionnaire, and one developed esophageal squamous cell carcinoma. Nine
      patients were lost to follow-up, and three would not answer the questionnaire
      (92.2% late follow-up). Postoperative dysphagia, odynophagia, chest pain, and
      heartburn was significantly improved at 1 year, 5 years, and late (5+ years)
      follow-up, with outcomes stable beyond 12 months. Seventy-seven percent of
      patients reported a good or excellent result (minimal or no symptoms) at 5 years
      and 73% at late follow-up. At late follow-up, 90% considered they had made the
      correct decision to undergo surgery. CONCLUSIONS: At minimum 5 years follow-up,
      laparoscopic cardiomyotomy for achalasia achieves effective and durable relief of
      symptoms, and most patients are satisfied with the outcome.

PMID- 20135241
TI  - Effect of concentration and substrate flow rate on isomaltulose production from
      sucrose by Erwinia sp. cells immobilized in calcium-alginate using packed bed
      reactor.
AB  - Isomaltulose was obtained from sucrose solution by immobilized cells of Erwinia
      sp. D12 using a batch and a continuous process. Parameters for sucrose conversion
      into isomaltulose were evaluated using both experimental design and response
      surface methodology. Erwinia sp. D12 cells were immobilized in different
      alginates, and the influence of substrate flow rate and concentration parameters
      to produce isomaltulose from sucrose were observed. Response surface methodology
      demonstrated that packed bed columns containing cells immobilized in low
      viscosity sodium alginate (250 cP) presented a mean isomaltulose conversion rate
      of 47%. In a continuous process, both sucrose substrate concentration and
      substrate flow rate parameters had a significant effect (p < 0.05) and influenced
      the conversion of sucrose into isomaltulose. Higher conversion rates of sucrose
      into isomaltulose, from 53-75% were obtained using 75 g of immobilized cells at a
      substrate flow rate of 0.6 mL/min.

PMID- 20135242
TI  - Maximizing algal growth in batch reactors using sequential change in light
      intensity.
AB  - Algal growth requires optimal irradiance. In photobioreactors, optimal light
      requirements change during the growth cycle. At low culture densities, a high
      incident light intensity can cause photoinhibition, and in dense algal cultures,
      light penetration may be limited. Insufficient light supply in concentrated algae
      suspensions can create zones of dissimilar photon flux density inside the
      reactor, which can cause suboptimal algal growth. However, growth of dense
      cultures can also be impaired due to photoinhibition if cells are exposed to
      excessively high light intensities. In order to simultaneously maintain optimal
      growth and photon use efficiency, strategies for light supply must be based on
      cell concentrations in the culture. In this study, a lipid-producing microalgal
      strain, Neochloris oleoabundans, was grown in batch photobioreactors. Growth
      rates and biomass concentrations of cultures exposed to constant light were
      measured and compared with the growth kinetic parameters of cultures grown using
      sequentially increasing light intensities based on increasing culture densities
      during batch growth. Our results show that reactors operated under conditions of
      sequential increase in irradiance levels yield up to a 2-fold higher biomass
      concentration when compared with reactors grown under constant light without
      negatively impacting growth rates. In addition, this tailored light supply
      results in less overall photon use per unit mass of generated cells.

PMID- 20135240
TI  - Mechanisms involved in antibody- and complement-mediated allograft rejection.
AB  - Antibody-mediated rejection has become critical clinically because this form of
      rejection is usually unresponsive to conventional anti-rejection therapy, and
      therefore, it has been recognized as a major cause of allograft loss. Our group
      developed experimental animal models of vascularized organ transplantation to
      study pathogenesis of antibody- and complement-mediated endothelial cell injury
      leading to graft rejection. In this review, we discuss mechanisms of antibody
      mediated graft rejection resulting from activation of complement by C1q- and MBL
      (mannose-binding lectin)-dependent pathways and interactions with a variety of
      effector cells, including macrophages and monocytes through Fcgamma receptors and
      complement receptors.

PMID- 20135243
TI  - Monitoring plasma heparin concentration in a patient with antiphospholipid
      syndrome.

PMID- 20135244
TI  - The role of L-arginine in inclusion complexes of omeprazole with cyclodextrins.
AB  - In this study, we investigate how the effect of L-arginine (ARG) and
      cyclodextrins upon omeprazole (OME) stability and solubility. The effect of the
      presence of ARG on the apparent stability constants (K(1:1)) of the inclusion
      complexes formed between OME and each cyclodextrin, beta-cyclodextrin (betaCD),
      and methyl-beta-cyclodextrin (MbetaCD) is studied by phase solubility diagrams
      and nuclear magnetic resonance (NMR) spectroscopy. The interaction of OME with
      those cyclodextrins, in the presence of ARG, is characterized using NMR
      spectroscopy and molecular dynamics simulations. ARG significantly increases the
      drug solubility and complex stability, in comparison to inclusion complexes
      formed in its absence. The effect is more pronounced for the OME:betaCD complex.
      ARG also contributes to a larger stability of OME when free in aqueous solution.
      The combination of ARG with cyclodextrins can represent an important tool to
      develop stable drug formulations.

PMID- 20135245
TI  - The anatomical variation of the lateral femoral cutaneous nerve in relation to
      the anterior superior iliac spine and the iliac crest.
AB  - The location of lateral femoral cutaneous nerve (LFCN) in relation to the
      anterior superior iliac spine (ASIS) and the iliac crest was investigated in 96
      embalmed cadaveric specimens. Fifty-six nerves (58.3%) passed medial to the ASIS.
      Twenty-two nerves (22.9%) passed at the ASIS. Eighteen nerves (18.8%) passed
      lateral to the ASIS. The LFCN is usually located at 2.1 +/- 0.8 to 3.9 +/- 1.0 cm
      below the crest in the range of 2-5 cm lateral to the ASIS, respectively. When
      the anterior iliac crest bone graft harvesting is planned, the anatomical
      variation in this area should be concerned to reduce the risk of LFCN injury.

PMID- 20135246
TI  - Primary failure of eruption (PFE)--clinical and molecular genetics analysis.
AB  - BACKGROUND: The term "primary failure of eruption" (PFE) refers to the complete
      or partial failure of a primary non-ankylosed tooth to erupt due to a disturbance
      of the eruption mechanism. Up to now, the molecular basis for this failure was
      unknown. PATIENTS AND METHODS: Four families were studied in whom at least two
      members were affected by non-syndromic PFE as part of a clinical and molecular
      genetics study. Radiological diagnostics (OPTs) were carried out in all patients
      and their unaffected relatives (control group). The genetic analysis included a
      genomewide linkage analysis followed by direct DNA sequencing of positional
      candidate genes. RESULTS: Starting from the index patients, we were able to
      reconstruct pedigrees over two and/or three generations in the families that
      indicated an autosomal-dominant mode of inheritance of non-syndromic PFE. Fifteen
      patients were diagnosed with PFE. Gender distribution was nearly equal (7 female,
      8 male). Molecular genetic analysis of the PTHR1 gene revealed three distinct
      heterozygous mutations (c.1050-3C>G; c.543+1G>A; c.463G>T). Unaffected persons
      exhibited no mutations. CONCLUSIONS: Knowledge of the genetic causes of non
      syndromic PFE can now be used for the differential diagnosis of eruption failure.
      It permits affected family members to be identified early and may lead to new
      treatment possibilities in the long term. The genetically-verified diagnosis of
      "primary failure of eruption" can protect patients and orthodontists from years
      of futile treatment, because orthodontic treatment alone does not lead to
      success. Moreover, it has a negative influence on unaffected teeth and areas of
      the jaw.

PMID- 20135247
TI  - The significance of RUNX2 in postnatal development of the mandibular condyle.
AB  - OBJECTIVE: RUNX2, in the Runt gene family, is one of the most important
      transcription factors in the development of the skeletal system. Research in
      recent decades has shown that this factor plays a major role in the development,
      growth and maturation of bone and cartilage. It is also important in tooth
      development, mechanotransduction and angiogenesis, and plays a significant role
      in various pathological processes, i.e. tumor metastasization. Mutations in the
      RUNX2 gene correlate with the cleidocranial dysplasia (CCD) syndrome, important
      to dentistry, particularly orthodontics because of its dental and orofacial
      symptoms. Current research on experimentally-induced mouse mutants enables us to
      study the etiology and pathogenesis of these malformations at the cellular and
      molecular biological level. This study's aim is to provide an overview of the
      RUNX2 gene's function especially in skeletal development, and to summarize our
      research efforts to date, which has focused on investigating the influence of
      RUNX2 on mandibular growth, which is slightly or not at all altered in many CCD
      patients. MATERIALS AND METHODS: Immunohistochemical analyses were conducted to
      reveal RUNX2 in the condylar cartilage of normal mice and of heterozygous RUNX2
      knockout mice in early and late growth phases; we also performed radiographic and
      cephalometric analyses. RESULTS: We observed that RUNX2 is involved in normal
      condylar growth in the mouse and probably plays a significant role in
      osteogenesis and angiogenesis. The RUNX2 also has a biomechanical correlation in
      relation to cartilage compartmentalization. At the protein level, we noted no
      differences in the occurrence and distribution of RUNX2 in the condyle, except
      for a short phase during the 4th and 6th postnatal weeks, so that one allele
      might suffice for largely normal growth; other biological factors may have
      compensatory effects. However, we did observe small changes in a few
      cephalometric parameters concerning the mandibles of heterozygous knockout
      animals. We discuss potential correlations to our findings by relating them to
      the most current knowledge about the RUNX2 biology.

PMID- 20135248
TI  - Does pregnancy or use of contraceptives influence adult facial changes?
AB  - OBJECTIVE: Aim of this study was to test the hypothesis that documented
      differences between males and females in adult facial changes are caused by
      pregnancy or the use of contraceptives. MATERIALS AND METHODS: Cephalograms were
      obtained of 96 females and 38 males (mean age 21.8 years and 22.4 years
      respectively), T1. The second cephalogram was taken 10.3 and 10.6 years later
      (T2). The subjects had not undergone orthodontic treatment or surgery during the
      observation period. Information on the number of births and use of oral
      contraceptives was available for each female, and they were divided into groups
      according to use (CP) or non-use (NCP) of contraceptive pills, and number of
      children born. RESULTS: The linear hard tissue changes were relatively small,
      none exceeding 2 mm. The S-N line increased in all groups - more in females than
      in males, with the greatest change in the women with three children group. The
      parameter Cd-Prgn increased more in males than in females. The angles SNA and SNB
      increased in the males and decreased in the females. The other angles decreased
      in males, while the changes were more variable in the females. The soft tissue
      changes varied greatly. Few of the differences between males and females were
      statistical significant. CONCLUSION: Few of the differences between adult males
      and females in facial changes are caused by pregnancies or the use of oral
      contraceptives.

PMID- 20135249
TI  - 3D soft tissue analysis--part 1: sagittal parameters.
AB  - OBJECTIVE: The aim of this study was to develop a reliable three-dimensional (3D)
      analysis of facial soft tissues. We determined the mean sagittal 3D values and
      relationships between sagittal skeletal parameters, and digitally recorded 3D
      soft tissue parameters. PATIENTS AND METHODS: A total of 100 adult patients
      (n(female) = 53, n(male) = 47) of Caucasian ethnic origin were included in this
      study. Patients with syndromes, cleft lip and palate, noticeable asymmetry or
      anomalies in the number of teeth were excluded. Arithmetic means for seven
      sagittal 3D soft tissue parameters were calculated. The parameters were analyzed
      biometrically in terms of their reliability and gender-specific differences. The
      3D soft tissue values were further analyzed for any correlations with sagittal
      cephalometric values. RESULTS: Reproducible 3D mean values were defined for 3D
      soft tissue parameters. We detected gender-specific differences among the
      parameters. Correlations between the sagittal 3D soft tissue and cephalometric
      measurements were statistically significant. CONCLUSION: 3D soft tissue analysis
      provides additional information on the sagittal position of the jaw bases and on
      intermaxillary sagittal relations. Further studies are needed to integrate 3D
      soft tissue analysis in future treatment planning and assessment as a supportive
      diagnostic tool.

PMID- 20135250
TI  - Biomechanical properties of orthodontic miniscrews. An in-vitro study.
AB  - OBJECTIVE: Comparing five commercially-available miniscrew types for skeletal
      anchorage with regard to the biomechanical properties influencing their primary
      stability. MATERIAL AND METHODS: Included in this study was a total of 196 self
      tapping and self-drilling miniscrews having a diameter of 2 mm (or the largest
      possible diameter of the manufacturer in question), a thread shaft length of 10
      mm, or the longest miniscrew supplied by the manufacturers. The screw types
      tested were the FAMI 2, Orlus mini-implant, T.I.T.A.N. Pin, tomas-pin and Vector
      TAS. Insertion and loosening torque measurements, and pullout tests in axial (0
      degrees), 20 degrees and 40 degrees directions, as well as test series with and
      without pilot hole drilling were performed. Bovine femoral heads having the same
      bone mineral density (BMD) were used as bone-testing material. RESULTS: Higher
      insertion torques were found for the cylindrical FAMI 2 screw, the conical Orlus
      mini-implant and the Vector TAS screw (with mean values of 39.2 Ncm, 32.1 Ncm and
      49.5 Ncm) than for the cylindrical T.I.T.A.N. pin and tomas-pin. Insertion
      without predrilling led the insertion torques of all five screws to rise
      significantly. We noted statistically significant differences among the five
      screws in the pullout tests. Those highly significant differences at axial (0
      degrees) and 20 degrees angles were not apparent at the 40 degrees pullout angle.
      Compared with the pullout forces (load) in the axial direction, the cylindrical
      screws' load values decreased markedly according to the angle (by up to -46.6%).
      The reduction in pullout force in conjunction with an increasing angle was much
      less pronounced in the conical screws (-0.8% to -29.0%). The tomas-pin
      demonstrated the highest pullout force and stiffness values throughout the tests.
      A total of five tomas-pins, two Orlus mini-implants and one FAMI 2 screw
      fractured during the pullout tests. CONCLUSIONS: Results from our insertion
      torque measurements suggest that a conical screw design will provide greater
      primary stability than cylindrical screw types. The cylindrical screw design's
      superiority was evident in the pullout tests. All the miniscrews' primary
      stability rose after drill-free insertion. The tomas-pin screws, although
      biomechanically superior to the other screws, were most prone to fracture.

PMID- 20135251
TI  - The use of MRI diagnostics in orthognathic surgery: prevalence of TMJ pathologies
      in Angle Class I, II, III patients.
AB  - AIM: Occasionally, undesirable post-surgical symptoms of temporomandibular
      disorder (TMD) and pain have been observed. The aim of this paper is to show how
      often and to which degree TMJ pathologies occur in orthognathic surgery
      candidates before surgery, making it recommendable to consider these TMJ
      pathologies during treatment planning. PATIENTS AND METHODS: Between 2002 and
      2004, Magnetic Resonance Imaging (MRI) of the TMJ were made in 58 randomly chosen
      orthognathic surgery patients. 69% of the patients were female, 31% were male.
      Age averaged 31.6 years (16-61 years). Gender and malocclusion (Class I, II and
      III) were looked at during analysis of the data (n = 58 patients, n = 116 TMJs).
      MRI scans were made at the beginning of treatment. We wanted to investigate the
      TMJ condition before surgery. RESULTS: The largest patients group of this study
      were the female Class II patients (n = 25). Most patients displayed an Angle
      Class II (53.4%). The Class III patients followed (32.8%). A Class I molar
      relationship was found in 13.8% of the studied patients. A similar distribution
      could be observed in the parameters we studied: 1. condyle (position,
      degeneration), 2. disc (position, degeneration, prolapse and reduction). 76% of
      the TMJs (66.7%) showed dorsocranial condylar displacement. 26 of the 114 studied
      condyles (22.8%) were dorsally displaced. 108 of the studied joints (94.7%)
      showed condylar displacement. In 31 TMJs (28,4%) we found moderate, in 25 joints
      (22.9%) severe and in 26 joints (23.9%) we observed slight condylar degeneration.
      Most discs were displaced ventrally (31%). 22 of the studied 113 discs (19.5%)
      were displaced medially. 93% of the studied discs were not positioned correctly.
      58 of the studied discs (58.6%) displayed flattening, in 8 (8%) we observed both
      flattening and disc adhesions. Two each of the studied TMJs had discs with
      perforations and adhesions or only perforations. In 57 (50.4%) of the studied
      discs we observed partial disc prolapse. Disc prolapse was total in 42.5% (n = 48
      TMJs) of the TMJs. Eight TMJs (7%) of the 113 TMJs we analyzed showed no disc
      prolapse. Disc reduction was total in 71 (62.8%) of the studied TMJs. 15% (n = 17
      TMJs) showed a partially reduced disc. 25 (22.1%) of the studied joints showed no
      disc reduction. CONCLUSION: Apparently, MRI scans of the TMJ are necessary in
      almost all potential orthognathic surgery patients to achieve optimal surgical
      results. Female Class II patients recruited the largest patient group among the
      studied collective. It is this group that deserves the greatest caution before
      and after surgery (TMJ pathologies!). In patients with jaw discrepancies, a TMJ
      examination should be made prior to surgery in order to be able to include the
      condition of the TMJs in the planning of treatment. This examination best
      includes Magnetic Resonance Imaging (MRI) and Manual Functional Analysis (MFA).

PMID- 20135253
TI  - [Severely dysplastic nevus: atypical Spitz nevus or melanoma in situ?].
AB  - A 31-year-old patient presented with a new, rapidly growing pigmented skin tumor
      on her left thigh. Several years previously a level 2 superficial spreading
      melanoma (SSM) with a tumor thickness of 0.45 mm had been removed from her left
      thigh. Dermatoscopic examination revealed asymmetric pigmentation of the tumor
      with branched streaks of variable thickness and irregular pseudopodia.
      Histological analysis showed it to be a severely dysplastic melanocytic nevus.

PMID- 20135266
TI  - Nosocomial infections in neonatal intensive care units: profile, risk factor
      assessment and antibiogram.
AB  - OBJECTIVE: To determine the profile and risk factors of neonatal nosocomial
      infections and determine the antibiotic susceptibilities of these isolates.
      METHODS: Cohort study was conducted at Kasturba Medical College, Mangalore, from
      July 2005 to September 2006. Neonates admitted for more than forty-eight hours in
      the NICU, who developed infections/sepsis as evidenced by the clinical findings
      were included in the study. Chi-square test, Proportion tests were used, P value
      of <0.05 was considered significant. RESULTS: Extended spectrum beta lactamase
      (ESBL) producing Klebsiella species and Methicillin resistant Staphylococcus
      aureus (MRSA) were the predominant nosocomial pathogens. Significant risk factors
      included prematurity, low birth weight and increased duration of hospital stay.
      CONCLUSION: A revised infection control program with emphasis on handwashing
      techniques and antibiotic cycling helped to control these hospital infections.

PMID- 20135267
TI  - Anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis.
AB  - OBJECTIVE: Prevalence and clinical significance of anti-cyclic citrullinated
      peptide (CCP) antibodies in Indian patients with juvenile idiopathic arthritis
      (JIA). METHODS: Anti-CCP antibodies were determined by enzyme-linked
      immunosorbent assay (ELISA) in 78 patients with JIA which included all 3 major
      subtypes of the disease: pauciarticular, polyarticular afld systemic onset.
      Values above 5 relative units were taken as positive. Associations between anti
      CCP antibodies and clinical and laboratory and radiological parameters were
      determined. RESULTS: Anti-CCP antibodies were positive in only 2 of 34 (5.9%)
      patients with pauciarticular JIA and 3 of 17 (17.6%) of systemic,.pnset JIA,
      whereas it was positive in 13 of 27 (48.1%) of polyarticular JIA patients (p <
      0.001). Furthermore, it was seen that among patients with polyarticular JIA, RF
      lgM positive patients had higher rate of anti-CCP antibody positivity with 7 of 8
      (87.5%) patients having positive anti-CCP antibody (p<0.001). Similarly, patients
      with erosions (11/19; p<0.001) and deformities (5/-10; p<0.001) were found to
      have significant association with anti-CCP antibody positivity. CONCLUSION: Anti
      CCP antibodies could be detected more frequently in the sera of JIA patients with
      severe manifestations like-erosions and deformity. It was also more significantly
      associated with seropositive polyarticular JIA than other types. It can be
      presumed from these results that anti-CCP antibodies can be used as a marker to
      predict severe course of JIA at the onset to guide optimal aggressive therapy.

PMID- 20135268
TI  - Transcutaneous bilirubin levels in healthy term and late preterm Indian neonates.
AB  - OBJECTIVE: To provide normative data for transcutaneous bilirubin (TcB)
      measurements in healthy term and late-preterm Indian neonates during first 72 h
      of age using a multiwavelength reflectance transcutaneous bilimeter. METHODS: TcB
      measurements were performed in healthy neonates (gestation 35 wk), in a well-baby
      ward, using a multiwavelength transcutaneous bilimeter (BiliCheck, SpectRx Inc,
      Norcross, GA). Age-specific percentiles values for each 6-h epoch starting at 0 h
      of age were calculated and an age-specific TcB nomogram was developed using
      different percentile values. Diagnostic ability of each percentile curve for
      prediction of hyperbilirubinemia, defined as requirement of phototherapy, was
      calculated. RESULTS: We performed 925 TcB measurements on 625 healthy newborn
      infants (gestation: 35 to 41 wk; age: 0 to 72 h; mean birth weight: 2808+/-437
      g). TcB increased in a linear manner with maximum rate of rise observed during
      first 24 h of age (50th percentile: 0.22 mg/dL/h). 50th percentile curve of age
      specific TcB nomogram had high negative predictive value (99.8%) and acceptable
      positive predictive value (16.4%) for prediction of hyperbilirubinemia.
      CONCLUSION: We provided age-specific nomogram of TcB for first 72 h of age in
      healthy term and late-preterm Indian neonates. Percentile curves and rate of rise
      in TcB may help in identification of neonates at low-risk of development of
      hyperbilirubinemia facilitating their safer discharge from the hospital.
      Diagnostic utility of this nomogram for predicting hyperbilirubinemia needs to be
      tested in a separate validation cohort.

PMID- 20135269
TI  - Profile of inborn errors of metabolism in a tertiary care centre PICU.
AB  - OBJECTIVE: To study the clinico-investigative profile and outcome of patients
      with inborn errors of metabolism (IEM) presenting to the pediatric intensive care
      unit (PICU). METHODS: Records of all patients admitted in tertiary care centre
      PICU between August 2007 and September 2008 with a diagnosis of IEM were
      retrieved the details of clinical presentation, laboratory results, treatment and
      outcome were noted and analysed. RESULTS: Eleven (2.6%) out of 420 PICU
      admissions during the study period had a diagnosis of IEM with a high mortality
      rate of 36%. Clinical presentation was quite varied. CONCLUSION: IEM are not
      uncommon in PICU. Simple biochemical tests and neuroimaging findings provide
      vital clues to the diagnosis of IEM.

PMID- 20135270
TI  - Prevalence of cholera in pediatric patients with acute dehydrating diarrhea.
AB  - OBJECTIVE: To estimate the prevalence of culture-confirmed cholera in patients
      with acute dehydrating diarrhea, at a tertiary care center in north India, during
      a 6-month period from March to August, 2006. METHODS: We studied 145 children,
      who presented to the pediatric emergency services of a tertiary care teaching
      hospital in north India with acute dehydrating diarrhea. Each patient had his/her
      stool sample collected for Vibrio cholerae culture and hanging drop preparation
      for darting motility. The stool specimen for hanging drop analysis was
      immediately transported to the emergency laboratory, where a trained technician
      prepared the slides and examined them for darting motility characteristic of
      Vibrio cholerae. RESULTS: V. cholerae was isolated in 36 (24.8%) patients. Forty
      nine (33.7%) patients had a positive hanging drop examination. Hanging drop
      examination had a sensitivity and specificity of 85.8% and 81.7%, respectively.
      Severe dehydration (OR 4.3; P<0.01) and hanging drop positivity (OR 12.42;
      P<0.001) were associated with higher odds of cholera after adjustment for other
      risk factors. CONCLUSION: Cholera is an important cause of acute watery diarrhea
      in pediatric patients in urban north India and should be ruled out in all
      children presenting with acute dehydrating diarrhea, particularly those with
      severe dehydration. Hanging drop test is useful for diagnosis in the emergency
      setting.

PMID- 20135271
TI  - Effect of wheat grass tablets on the frequency of blood transfusions in
      Thalassemia Major.
AB  - Forty patients of Thalassemia Major children were treated with wheat grass
      tablets (WGT). The mean hemoglobin in the pre WGT was 8.54 +/- 0.33 g% whereas in
      WGT period was 9.13 +/- 0.14 g% (p < 0.001). The mean blood transfused as packed
      cells in pre WGT period was 326.82 +/- 74.10 ml/kg/year whereas during WGT period
      it was 256.39 +/- 45.47 ml/kg/year. The percentage difference in the amount of
      packed cells transfused in pre WGT and WGT period was 18.02 +/- 22.96 (p <
      0.001). The decrease in the blood transfusion requirements was by 25% or more in
      20 (60.6%) cases. The mean interval between the consecutive blood transfusions in
      Pre WGT period was 18.78 +- 4.48 days whereas in WGT period was 24.16 +- 4.78
      days (p < 0.001). Wheat grass has the potential to increase the Hb levels,
      increase the interval between blood transfusions and decrease the amount of total
      blood transfused in Thalassemia Major patients.

PMID- 20135272
TI  - Imaging in mediastinal neuroblastoma.

PMID- 20135273
TI  - Metalloproteases and the degradome.
AB  - Metalloproteases comprise a heterogeneous group of proteolytic enzymes whose main
      characteristic is the utilization of a metal ion to polarize a water molecule and
      perform hydrolytic reactions. These enzymes represent the most densely populated
      catalytic class of proteases in many organisms and play essential roles in
      multiple biological processes. In this chapter, we will first present a general
      description of the complexity of metalloproteases in the context of the
      degradome, which is defined as the complete set of protease genes encoded by the
      genome of a certain organism. We will also discuss the functional relevance of
      these enzymes in a large variety of biological and pathological conditions.
      Finally, we will analyze in more detail three families of metalloproteases: ADAMs
      (a disintegrin and metalloproteinase), ADAMTSs (ADAMs with thrombospondin
      domains), and MMPs (matrix metalloproteinases) which have a growing relevance in
      a number of human pathologies including cancer, arthritis, neurodegenerative
      disorders, and cardiovascular diseases.

PMID- 20135274
TI  - Mouse models of MMP and TIMP function.
AB  - As their name implies, matrix metalloproteinases (MMPs) are thought to be
      responsible for the turnover of connective tissue proteins, a function that is
      indeed performed by some family members. However, matrix degradation is possibly
      not the predominant function of these enzymes. Several studies have demonstrated
      that MMPs also act on a variety of non-matrix extracellular proteins, such as
      cytokines, chemokines, receptors, junctional proteins, and antimicrobial
      peptides, to mediate a wide range of biological processes, such as repair,
      immunity, and angiogenesis. Our understanding of the many, diverse and, at times,
      unexpected functions of MMPs largely arose from the use of gene-targeted mice. In
      this chapter, we discuss the phenotypes of some MMP-deficient and TIMP-null mice
      and strategies and pitfalls in targeted mutagenesis.

PMID- 20135275
TI  - Expression of recombinant MMP-28 in mammalian cells.
AB  - The expression of a recombinant MMP in a mammalian cell line can be useful, e.g.,
      for purification of the enzyme, to characterize function of the enzyme, or to
      uncover its substrates. In this chapter, we have therefore documented our
      experience with the recently discovered MMP-28.

PMID- 20135276
TI  - Expression of recombinant matrix metalloproteinases in Escherichia coli.
AB  - Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases
      that are capable of cleaving all of the components of the extracellular matrix
      (ECM). The role that the MMPs play in normal and pathological conditions has long
      been of interest. The mechanisms by which the MMPs cleave the different
      components of the ECM have been examined extensively. Some of these studies have
      been made possible, in part, by the ability to express recombinant MMPs. These
      recombinant MMPs have been utilized in both structural and functional studies. In
      addition, future studies can benefit from the availability of recombinant MMPs.
      Recombinant MMPs have been expressed in mammalian and bacterial recombinant
      expression systems. The most common bacterial expression system employed for this
      has been the utilization of expression plasmids in Escherichia coli. This has
      resulted in the production of a large amount of protein in a short period of
      time. The expression of a recombinant truncated form of human stromelysin-1 (MMP
      3) will be used to illustrate the methods utilized for the expression of a MMP in
      E. coli. This will include discussions about the expression vector, the cloning
      of the MMP cDNA into the expression vector, protein induction, protein
      extraction, protein refolding and purification, and protein characterization.

PMID- 20135277
TI  - Expression of recombinant ADAMTS in insect cells.
AB  - The "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS)
      enzymes are secreted proteinases involved in development, blood clotting and the
      turnover of extracellular matrix. Manufacturing recombinant enzyme presents quite
      a challenge due to the presence of disulphide bridges, the large size and modular
      structure. A sub-group of these enzymes are known as "aggrecanases" and it is
      likely that they are involved in a number of pathologies related to increased
      turnover of the extracellular matrix, particularly in tissues where the
      concentration of proteoglycans is high, such as cartilage and the central nervous
      system. We have expressed three of these enzymes, ADAMTS-1, -4 and -5, in insect
      cells using plasmid-based systems.

PMID- 20135278
TI  - Expression and purification of membrane-type MMPs.
AB  - Matrix metalloproteinases (MMPs) modulate cell-cell and cell-matrix interactions
      and the membrane-type MMPs (MT-MMPs) are especially important for pericellular
      proteolysis. Understanding the activity, regulation, and function of MT-MMPs
      would provide important insight for ongoing research in many diseases including
      cancer, fibrosis, and autoimmune diseases. In this chapter, we introduce the
      methods to express and purify recombinant MT-MMPs using Escherichia coli or
      mammalian cells, as well as how to detect the activity of MT-MMPs in proMMP-2
      activation using gelatin zymography.

PMID- 20135279
TI  - Refolding of TIMP-2 from Escherichia coli inclusion bodies.
AB  - The TIMP proteins contain six intramolecular disulfide bonds and form unfolded
      insoluble aggregates when expressed in E. coli. Eukaryotic expression systems
      provide the necessary post-translational modification apparatus to produce
      authentic TIMP but are comparatively slow and more expensive. This chapter
      describes the production of native TIMP-2 (both full-length and the N-terminal
      domain) from E. coli by in vitro refolding. The technique allows high-level
      intracellular expression and efficient isolation of the recombinant product
      without the use of fusion tags or partners. Protein purity after ion exchange and
      gel filtration chromatography was judged to be greater than 95% with yields of 15
      mg/L from LB medium and 10 mg/L from minimal medium.

PMID- 20135280
TI  - Purification of MMPs and TIMPs.
AB  - A number of matrix metalloproteinases (MMPs) and their endogenous inhibitors
      called tissue inhibitors of metalloproteinases (TIMPs) from natural sources have
      been identified. This chapter describes the purification methods of MMPs-1, -2, 
      3, -7, -8, -9, -10, -12, and -13 and TIMPs-1 and -2. The sources of the proteins
      and assay methods to detect their activities are also described.

PMID- 20135281
TI  - Real-time PCR expression profiling of MMPs and TIMPs.
AB  - Quantitative reverse transcriptase polymerase chain reaction enables the accurate
      quantification of gene expression in cultured cells or small tissue samples. In
      this chapter, we describe the use of Taqman((R)) technology to measure expression
      of matrix metalloproteinases and related genes.

PMID- 20135282
TI  - Analysis of the degradome with the CLIP-CHIP microarray.
AB  - The degradome microarray - CLIP-CHIP - is a dedicated and focused array that
      allows the analysis of all proteases, non-proteolytic homologs, and protease
      inhibitor gene transcripts in the human and murine genomes at the mRNA transcript
      level.Based on unique 70-mer oligonucleotides, designed to match parts of the
      sequence of known or predicted protease and inhibitor mRNAs in both species and
      printed on a glass-matrix surface, the CLIP-CHIP microarray can be used to
      analyze differentially expressed protease and inhibitor gene products and give
      expression profiles for any analyzed sample.

PMID- 20135283
TI  - In situ hybridization for metalloproteinases and their inhibitors.
AB  - In situ hybridization (ISH) is an invaluable tool in understanding tissue
      specific gene expression and gene regulation within a spatial context and at a
      resolution that is not possible by any other method. In this chapter, we provide
      ISH methodology that has successfully been applied to the detection of
      metalloproteinases and their inhibitors.

PMID- 20135284
TI  - Immunohistochemistry of MMPs and TIMPs.
AB  - Immunohistochemistry is a useful and powerful method to determine the cells
      responsible for the production of MMPs and TIMPs and localize them to the tissue
      areas where they are functioning. This chapter describes the detailed methods of
      the immunohistochemistry applied to human pathological tissues using commercially
      available monoclonal antibodies against MMPs and TIMPs. Information about the
      monoclonal antibodies and solution of the problems with immunostaining is also
      provided.

PMID- 20135285
TI  - Single nucleotide polymorphism genotyping in MMP genes: the 5' nuclease assay.
AB  - Many molecular genetic studies of human diseases involve determining the
      genotypes for single nucleotide polymorphisms. This chapter summarises a number
      of different techniques for the single nucleotide polymorphism genotyping which
      can be applied to MMP genes. The chapter also provides a protocol and technical
      notes for the 5'-nuclease assay, one of the most commonly used genotyping
      techniques.

PMID- 20135286
TI  - Methods for studying activation of matrix metalloproteinases.
AB  - The degradation of the extracellular matrix during development and in disease is
      thought to result from the combined action of several proteolytic enzyme systems,
      including the matrix metalloproteinases (MMPs), serine proteinases, and cysteine
      proteinases. The majority of the soluble MMPs are synthesized as proenzymes which
      require extracellular activation in order to gain proteolytic activity and the
      analysis of their activation mechanism is a prerequisite for understanding MMP
      mediated proteolysis.The emphasis of this chapter is the provision of the
      experimental tools to study MMP activation in vitro and in cellular model
      systems. Hence, we use the activation of procollagenase-3 (proMMP-13) and
      progelatinase A (proMMP-2) as examples of the methods used.

PMID- 20135287
TI  - Assay of matrix metalloproteinases against matrix substrates.
AB  - The assays described allow the activity of members of the matrix
      metalloproteinase (MMP) family that degrade collagen, gelatin and casein
      substrates to be measured. The protocols described include the preparation of
      radiolabeled substrates, methods for the separation of degraded product from
      undegraded substrate, and methods for the activation of MMPs. The advantages and
      disadvantages of these methods are discussed in relation to immunoassays that
      measure the amount of individual MMPs.

PMID- 20135288
TI  - Zymography and reverse zymography for detecting MMPs and TIMPs.
AB  - Zymography is the electrophoretic separation of proteins through a polyacrylamide
      gel containing a proteolytic substrate. After denaturing (but nonreducing)
      electrophoresis, proteins are renatured and incubated in an appropriate buffer
      for proteolytic activity. Clear zones of lysis in the stained gel indicated
      active proteinases. Reverse zymography is a similar technique to detect
      proteinase inhibitors. After renaturing of proteins, the gel is incubated with
      metalloproteinases which digest the substrate incorporated into the gel.
      Inhibitors are shown as dark zones of inhibition against a clear background upon
      staining.

PMID- 20135289
TI  - In situ zymography.
AB  - In situ zymography is a unique laboratory technique that enables the localisation
      of matrix-degrading metalloproteinase (MMP) activity in histological sections.
      Frozen sections are placed on glass slides coated with fluorescently labelled
      matrix proteins. After incubation MMP activity can be observed as black holes in
      the fluorescent background due to proteolysis of the matrix protein.
      Alternatively frozen sections can be incubated with matrix proteins conjugated to
      quenched fluorescein. Proteolysis of the substrate by MMPs leads to the release
      of fluorescence. This technique can be combined with immunohistochemistry to
      enable co-location of proteins such as cell type markers or other proteins of
      interest. Additionally, this technique can be adapted for use with cell cultures,
      permitting precise location of MMP activity within cells, time-lapse analysis of
      MMP activity and analysis of MMP activity in migrating cells.

PMID- 20135290
TI  - Near-infrared optical proteolytic beacons for in vivo imaging of matrix
      metalloproteinase activity.
AB  - The exuberant expression of proteinases by tumor cells has long been associated
      with the breakdown of the extracellular matrix, tumor invasion, and metastasis to
      distant organs. There are both epidemiological and experimental data that support
      a causative role for proteinases of the matrix metalloproteinase (MMP) family in
      tumor progression. Optical imaging techniques provide an extraordinary
      opportunity for non-invasive "molecular imaging" of tumor-associated proteolytic
      activity. The application of optical proteolytic beacons for the detection of
      specific proteinase activities associated with tumors has several potential
      purposes: (1) Detection of small, early-stage tumors with increased sensitivity
      due to the catalytic nature of the proteolytic activity, (2) diagnosis and
      prognosis to distinguish tumors that require particularly aggressive therapy or
      those that will not benefit from therapy, (3) identification of tumors
      appropriate for specific anti-proteinase therapeutics and optimization of drug
      and its dose based on determination of target modulation, and (4) as an indicator
      of the efficacy of proteolytically activated pro-drugs. This chapter describes
      the synthesis, characterization, and application of reagents that use visible and
      near-infrared fluorescence resonance energy transfer (FRET) fluorophore pairs to
      detect and measure MMP proteolytic activity in tumors in murine models of cancer.

PMID- 20135291
TI  - Neoepitope antibodies against MMP-cleaved and aggrecanase-cleaved aggrecan.
AB  - Neoepitope antibodies recognize the newly created N or C terminus of protein
      degradation products but fail to recognize the same sequence of amino acids
      present in intact or undigested protein. Aggrecan neoepitope antibodies have been
      pivotal in studies determining the contribution of matrix metalloproteinases
      (MMPs) and aggrecanases to aggrecanolysis. In particular, an antibody to the
      A(374)RGSV N terminus was instrumental in the landmark discovery of the
      aggrecanases, ADAMTS-4 and ADAMTS-5. Antibodies to neoepitopes at the major MMP
      cleavage site DIPEN(341)/(342)FFGVG helped to distinguish MMP-driven aggrecan
      loss from aggrecanase-driven aggrecan loss and identified a role for MMPs in late
      stage disease. More recently, neoepitope antibodies that recognize cleavage sites
      in the chondroitin sulphate-rich region of aggrecan have been used to show that
      aggrecanase cleavage proceeds in a defined manner, beginning at the C terminus
      and proceeding to the signature cleavage at NITEGE(373)/(374)ARGSV in the
      interglobular domain. Work with the C-terminal neoepitope antibodies has
      underscored the need to use a suite of neoepitope antibodies to fully describe
      aggrecanolysis in vitro. In this chapter, we describe the production of two
      aggrecan neoepitope antibodies as examples: the monoclonal anti-FFGVG antibody
      (AF-28) and the polyclonal anti-DIPEN antisera.

PMID- 20135292
TI  - In vitro model of cartilage degradation.
AB  - This 14-day model of cartilage breakdown involves stimulation of bovine nasal
      cartilage with a combination of interleukin-1 and oncostatin M. Media is
      harvested on days 7 and 14 and the conditioned media and remaining cartilage at
      day 14 assayed for the levels of proteoglycan and collagen fragments using
      biochemical assays.

PMID- 20135293
TI  - Immunoassays for collagenase-mediated cleavage of type I and II collagens.
AB  - This chapter describes the production and characterization of antibodies raised
      against neoepitopes in collagenase-cleaved collagen. It also details the
      development, validation, and use of immunoassays using such antibodies to measure
      specifically collagenase-mediated cleavage.

PMID- 20135294
TI  - Collagen degradation assays.
AB  - The biochemistry of collagen makes the assay of its degradation complex. Hidden
      epitopes are linear amino acid sequences that are not normally available for
      antibody binding when they are contained within an intact helical structure, but
      they become exposed once the collagen triple helix has been cleaved and
      denatured. This chapter describes the use of an antibody raised against such an
      epitope, combined with selective proteolytic extraction, to assay collagen
      degradation.

PMID- 20135295
TI  - Analysis of MMP-dependent cell migration and invasion.
AB  - Analysing cell migration and invasion is of interest to many investigators as
      they mimic a part of physiological or pathological events. In this chapter,
      methods to analyse MMP-dependent 2D and 3D cell migration are described in
      detail. To study 2D cell migration, the phagokinetic track motility assay can be
      used. To study 3D cell migration, Matrigel invasion assay or microcarrier beads
      invasion assay can be used to obtain quantitative results.

PMID- 20135296
TI  - Using fluorogenic peptide substrates to assay matrix metalloproteinases.
AB  - A continuous assay method, such as the one that utilizes an increase in
      fluorescence upon hydrolysis, allows for rapid and convenient kinetic evaluation
      of proteases. To better understand MMP behaviors and to aid in the design of MMP
      inhibitors, a variety of sequence specificity, phage display, and combinatorial
      chemistry studies have been performed. Results of these studies have been
      valuable for defining the differences in MMPs and for creating quenched
      fluorescent substrates that utilize fluorescence resonance energy transfer
      (FRET)/intramolecular fluorescence energy transfer (IFET). FRET triple-helical
      substrates have been constructed to examine the collagenolytic activity of MMP
      family members. The present chapter provides an overview of MMP and related FRET
      substrates and describes how to construct and utilize these substrates.

PMID- 20135297
TI  - Kinetic analysis of the inhibition of matrix metalloproteinases: lessons from the
      study of tissue inhibitors of metalloproteinases.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are a group of highly potent
      inhibitors of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases
      (ADAMs). The high affinity and "tight-binding" nature of the inhibition of MMPs
      or ADAMs by TIMPs presents challenges for the determination of both equilibrium
      and dissociation rate constants of these inhibitory events. Methodologies that
      enable some of these challenges to be overcome are described in this chapter and
      represent valuable lessons for the in vitro assessment of MMP or ADAM inhibitors
      within a drug discovery context.

PMID- 20135298
TI  - Identification of cellular MMP substrates using quantitative proteomics: isotope
      coded affinity tags (ICAT) and isobaric tags for relative and absolute
      quantification (iTRAQ).
AB  - Identification of protease substrates is essential to understand the functional
      consequences of normal proteolytic processing and dysregulated proteolysis in
      disease. Quantitative proteomics and mass spectrometry can be used to identify
      protease substrates in the cellular context. Here we describe the use of two
      protein labeling techniques, Isotope-Coded Affinity Tags (ICAT and Isobaric Tags
      for Relative and Absolute Quantification (iTRAQ), which we have used successfully
      to identify novel matrix metalloproteinase (MMP) substrates in cell culture
      systems (1-4). ICAT and iTRAQ can label proteins and protease cleavage products
      of secreted proteins, protein domains shed from the cell membrane or pericellular
      matrix of protease-transfected cells that have accumulated in conditioned medium,
      or cell surface proteins in membrane preparations; isotopically distinct labels
      are used for control cells. Tryptic digestion and tandem mass spectrometry of the
      generated fragments enable sequencing of differentially labeled but otherwise
      identical pooled peptides. The isotopic tag, which is unique for each label,
      identifies the peptides originating from each sample, for instance, protease
      transfected or control cells, and comparison of the peak areas enables relative
      quantification of the peptide in each sample. Thus proteins present in altered
      amounts between protease-expressing and null cells are implicated as protease
      substrates and can be further validated as such.

PMID- 20135299
TI  - Mechanism-based profiling of MMPs.
AB  - The recognition that the successful clinical use of MMP inhibitors will require
      quantitative correlation of MMP activity with disease type, and to disease
      progression, has stimulated intensive effort toward the development of sensitive
      assay methods, improved analytical methods for the determination of the
      structural profile for MMP-sub-type inhibition, and the development of new
      methods for the determination - in both quantitative and qualitative terms - of
      MMP activity. This chapter reviews recent progress toward these objectives, with
      particular emphasis on the quantitative and qualitative profiling of MMP activity
      in cells and tissues. Quantitative determination of MMP activity is made from the
      concentration of the MMP from the tissue, using immobilization of a broad
      spectrum MMP inhibitor on a chromatography resin. Active MMP, to the exclusion of
      MMP zymogens and endogenous TIMP-inhibited MMPs, is retained on the column.
      Characterization of the MMP sub-type(s) follows from appropriate analysis of the
      active MMP eluted from the resin. Qualitative determination of MMP involvement in
      disease can be made using an MMP sub-type-selective inhibitor. The proof of
      principle, with respect to this qualitative determination of the disease
      involvement of the gelatinase MMP-2 and MMP-9 sub-types, is provided by the class
      of thiirane-based MMP mechanism-based inhibitors (SB-3CT as the prototype).
      Positive outcomes in animal models of disease having MMP-2 and/or -9 dependency
      follow administration of this MMP inhibitor, whereas this inhibitor is inactive
      in disease models where other MMPs (such as MMP-14) are involved.

PMID- 20135300
TI  - Provenancing of archeological pumice finds from North Sinai.
AB  - Seven pumice samples from excavations in North Sinai have been investigated with
      respect to their geochemical composition. This type of volcanic rock has been
      used as an abrasive and thus has been an object of trade since antiquity. With
      the help of Instrumental Neutron Activation Analysis, six of these Bronze Age
      samples could be correlated to their volcanic sources on the islands of
      Santorini, Nisyros and Giali (Greece) using the typical element concentrations
      ("chemical fingerprint"). The source of one pumice sample remains unidentified
      excluding, however, the Santorini eruption as a possible source. The concluding
      section of this article discusses the possible contribution, however indirect, of
      the pumice from Sinai and elsewhere in the Eastern Mediterranean to the
      controversial issue of the accurate date of the "Minoan" eruption of Santorini.

PMID- 20135302
TI  - Uterus conserving prolapse surgery--what is the chance of missing a malignancy?
AB  - INTRODUCTION AND HYPOTHESIS: Recently, there has been a move towards uterine
      preserving surgery in the management of pelvic organ prolapse. The negative
      implications of such surgery have not been delineated. This study aims to
      identify the risk of finding an unexpected malignancy in these cases. METHODS: A
      database containing details of vaginal hysterectomies performed over a 10-year
      period was searched. Women who underwent surgery for uterine prolapse were
      included. Women with other indications for surgery and those who presented with
      symptoms relating to endometrial or cervical malignancy were excluded. As this is
      a non-interventional observational study, formal ethical approval was not
      obtained. RESULTS: Out of 517 women who underwent a vaginal hysterectomy for
      prolapse, four cases of endometrial carcinoma were identified giving an incidence
      of 0.8%. CONCLUSIONS: Conserving a prolapsed uterus without further
      investigations runs the risk of missing women with endometrial malignancy.

PMID- 20135303
TI  - Perineal descent and patients' symptoms of anorectal dysfunction, pelvic organ
      prolapse, and urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this dynamic magnetic resonance (MR)
      imaging study was to assess the relation between the position and mobility of the
      perineum and patients' symptoms of pelvic floor dysfunction. METHODS: Patients'
      symptoms were measured with the use of validated questionnaires. Univariate
      logistic regression analyses were used to study the relationship between the
      questionnaires domain scores and the perineal position on dynamic MR imaging, as
      well as baseline characteristics (age, body mass index, and parity). RESULTS:
      Sixty-nine women were included in the analysis. Only the domain score genital
      prolapse was associated with the perineal position on dynamic MR imaging. This
      association was strongest at rest. CONCLUSIONS: Pelvic organ prolapse symptoms
      were associated with the degree of descent of the perineum on dynamic MR imaging.
      Perineal descent was not related to anorectal and/or urinary incontinence
      symptoms.

PMID- 20135304
TI  - Long-term durability of pubovaginal fascial slings in women who then become
      pregnant and deliver.
AB  - INTRODUCTION AND HYPOTHESIS: Pubovaginal fascial slings are commonly performed
      after childbearing is completed. Limited data is available regarding women who
      become pregnant following a sling procedure. METHODS: Three hundred forty-one
      women of childbearing age underwent pubovaginal sling surgery at our institution
      from July 1993 to December 2005. All patients were sent a questionnaire regarding
      their incontinence and health status. RESULTS: Nine women who delivered following
      surgery were identified (seven vaginal and two cesarean sections). Overall, five
      remained dry, three had no change in continence, and one noted worsening
      incontinence. Four women completed questionnaires (two vaginal and two caesarean
      sections). One patient who delivered vaginally reported high symptom scores and
      dissatisfaction while the remaining three reported low symptom scores and
      satisfaction. CONCLUSIONS: The pubovaginal fascial sling is a durable option for
      women with reproductive potential. Given our results, both vaginal delivery and
      cesarean section appear to be acceptable modes of delivery in this patient
      population.

PMID- 20135305
TI  - Clinical and pathophysiological correlates of the symptom severity of stress
      urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The pathophysiology of stress urinary incontinence
      (SUI) is multifactorial. The aim of this study was to explore the factor
      determining the symptom severity of SUI. METHODS: One hundred twenty-four women
      with SUI were retrospectively investigated. Clinical data for analyses included
      demographics, pelvic organ prolapse quantification, SUI severity using a 4-point
      Likert scale, ultrasound, 1-h pad tests, and urodynamic studies. Data were
      analyzed using the Spearman's rho test and Kruskal-Wallis test. RESULTS: The
      symptom severity was not correlated with risk factors of SUI or the morphologic
      manifestations representing urethral support defect, but was significantly
      correlated with urine loss on 1-h pad test, Valsalva leak point pressure (VLPP)
      grading, and maximum urethral closure pressure (MUCP). Women with higher SUI
      severity had greater urine loss on 1-h pad tests, worse VLPP grading, and lower
      MUCP. CONCLUSIONS: Urethral sphincter function appears to be an important
      determinant for the symptom severity of SUI.

PMID- 20135306
TI  - Evaluation of sample preparation methods for elastomer digestion for further
      halogens determination.
AB  - In this work, three sample preparation methods were evaluated for further halogen
      determination in elastomers containing high concentrations of carbon black.
      Samples of nitrile-butadiene rubber, styrene-butadiene rubber, and ethylene
      propylene-diene monomer elastomers were decomposed using oxygen flask combustion
      and microwave-induced combustion (MIC) for further Br and Cl determination by ion
      chromatography (IC), inductively coupled plasma optical emission spectrometry
      (ICP OES), and inductively coupled plasma mass spectrometry (ICP-MS). Extraction
      assisted by microwave radiation in closed vessels was also evaluated using water
      or alkaline solution. Digestion by MIC was carried out using 50 mmol l(-1)
      (NH(4))(2)CO(3) as the absorbing solution. The effect of the reflux step was also
      evaluated. Accuracy was evaluated using certified reference materials with
      polymeric matrix composition and by comparison of results using neutron
      activation analysis. Agreement for Br and Cl was better than 95% by MIC using 5
      min of reflux, and no statistical difference was found using IC, ICP OES, and ICP
      MS for determination of both analytes. For MIC, the relative standard deviation
      (RSD) was lower than 5%. Using extraction in closed vessels, a high amount of
      residues was observed, and recoveries were lower than 45% for both analytes. For
      oxygen flask combustion, the agreement was similar using MIC but RSD was higher
      (20%). The residual carbon content, an important parameter used to evaluate the
      digestion efficiency, was always below 1% for MIC. Using MIC, it was possible to
      digest elastomers with high efficiency, resulting in a single solution suitable
      for halogen determination by different techniques.

PMID- 20135307
TI  - Integrated analysis of halogenated organic pollutants in sub-millilitre volumes
      of venous and umbilical cord blood sera.
AB  - A rapid, robust and economical method for the analysis of persistent halogenated
      organic compounds in small volumes of human serum and umbilical cord blood is
      described. The pollutants studied cover a broad range of molecules of
      contemporary epidemiological and legislative concern, including
      polychlorobiphenyls (PCBs), polychlorobenzenes (CBs), hexachlorocyclohexanes
      (HCHs), DDTs, polychlorostyrenes (PCSs) and polybromodiphenyl ethers (PBDEs).
      Extraction and clean-up with n-hexane and concentrated sulphuric acid was
      followed with analysis by gas chromatography coupled to electron capture (GC-ECD)
      and GC coupled to negative ion chemical ionisation mass spectrometry (GC-NICI
      MS). The advantages of this method rest in the broad range of analytes and its
      simplicity and robustness, while the use of concentrated sulphuric acid
      extraction/clean-up destroys viruses that may be present in the samples. Small
      volumes of reference serum between 50 and 1000 microL were extracted and the
      limits of detection/quantification and repeatability were determined. Recoveries
      of spiked compounds for the extraction of small volumes (> or = 300 microL) of
      the spiked reference serum were between 90% and 120%. The coefficients of
      variation of repeatability ranged from 0.1-14%, depending on the compound.
      Samples of 4-year-old serum and umbilical cord blood (n = 73 and 40,
      respectively) from a population inhabiting a village near a chloro-alkali plant
      were screened for the above-mentioned halogenated pollutants using this method
      and the results are briefly described.

PMID- 20135308
TI  - An enzyme-linked immunosorbent assay to compare the affinity of chemical
      compounds for beta-amyloid peptide as a monomer.
AB  - Abeta(1-42) is the proteolytic cleavage product of cleavage of the amyloid
      precursor protein by beta- and gamma-secretases. The aggregation of Abeta(1-42)
      plays a causative role in the development of Alzheimer's disease. To lock Abeta(1
      42) in a homogenous state, we embedded the Abeta(1-42) sequence in an
      unstructured region of Bcl-x(L). Both the N-terminus and the C-terminus of
      Abeta(1-42) were constrained in the disordered region, whereas the conjunction
      did not introduce any folding to Abeta(1-42) but maintained the sequence as a
      monomer in solution. With Bcl-x(L)-Abeta(42), we developed an enzyme-linked
      immunosorbent assay to compare the affinity of compounds for monomeric Abeta(1
      42). Bcl-x(L)-Abeta(42) was coated on a microplate and this was followed by
      incubation with different concentrations of compounds. Compounds binding to Leu17
      Val24 of Abeta(1-42) inhibited the interaction between Bcl-x(L)-Abeta(42) and
      antibody 4G8. The method can not only reproduce the activities of the reported
      Abeta(1-42) inhibitors such as dopamine, tannin, and morin but can also
      differentiate decoy compounds that do not bind to Abeta(1-42). Remarkably, using
      this method, we discovered a new inhibitor that binds to monomeric Abeta(1-42)
      and inhibits Abeta(1-42) fibril formation. As the structure of Bcl-x(L)-Abeta(42)
      monomer is stable in solution, the assay could be adapted for high-throughput
      screening with a series of antibodies that bind the different epitopes of Abeta(1
      42). In addition, the monomeric form of the Abeta(1-42) sequence in Bcl-x(L)
      Abeta(42) would also facilitate the identification of Abeta(1-42) binding
      partners by coimmunoprecipitation, cocrystallization, surface plasmon resonance
      technology, or the assay as described here.

PMID- 20135309
TI  - Toxicological responses of red-backed salamander (Plethodon cinereus) exposed to
      aged and amended soils containing lead.
AB  - The use of lead in military and civilian small arms projectiles is widely
      acknowledged to have resulted in high soil lead concentrations at many small arms
      ranges. These ranges are often adjacent to wildlife habitat or have become
      habitat when no longer used. To assess the potential toxicity of lead to
      terrestrial amphibians in contaminated areas, we exposed 100 red-backed
      salamanders (Plethodon cinereus) to either a control soil or one of four soil
      treatments amended with lead acetate for 28 days. Analytical mean soil
      concentrations were 14 (control), 553, 1700, 4700, and 9167 mg Pb/kg soil dry
      weight. An additional 60 salamanders were also exposed for 28 days to one of six
      field-collected soil samples from a small arms range and a skeet range. The field
      soil concentrations ranged from 11 (background) to 16,967 mg Pb/kg soil dry
      weight. Food consisted of uncontaminated flightless Drosophila melanogaster.
      Salamander survival was reduced in amended soil treatments of 4700 and 9167 mg/kg
      by 15% and 80%, respectively. Inappetence was observed at 4700 and 9167 mg/kg and
      growth decreased in the 9167 mg/kg treatment. Total white blood cells decreased
      32% at 4700 mg/kg compared to controls and were 22% lower in the 9167 mg/kg
      treatment. In contrast, survival was 100% for all field-collected soils with no
      hematological effects. At 16,967 mg/kg there was evidence of soil avoidance and
      decreased growth. These data suggest marked differences in toxicity and
      bioavailability of the lead-amended soil in contrast to the field-collected soil
      containing lead.

PMID- 20135310
TI  - Chemotherapeutic potential of 9-phenyl acridine: biophysical studies on its
      binding to DNA.
AB  - Acridines and their derivatives are well-known probes for nucleic acids as well
      as being relevant in the field of drug development to establish new
      chemotherapeutic agents. We have shown from molecular modelling studies that 9
      phenyl acridine and some of its derivatives can act as inhibitors of
      topoisomerase I and thus have potential to act as anticancer agents. Rational
      design of new compounds for therapeutics requires knowledge about their
      structural stability and interactions with various cellular macromolecules. In
      this regard it is important to know how these molecules would interact with DNA.
      Here we report the interaction of 9-phenyl acridine (ACPH) with calf thymus DNA
      (CT-DNA) based on various biophysical and molecular modelling studies.
      Spectrophotometric studies indicated that ACPH binds to CT-DNA. DNA melting
      studies revealed that binding of ACPH to CT-DNA resulted in a small increase in
      melting temperature, which is unlikely in case of classical intercalator; rather,
      it indicates external binding. Viscosity measurements show that ACPH exhibits
      groove binding. Competitive binding of ACPH to CT-DNA pre-bound to ethidium
      bromide (EB) showed slow quenching. Measurement of the binding constant of ACPH
      by fluorescent intercalator displacement (FID) assay corroborated the notion that
      there was groove binding. Molecular modelling studies also supported this
      finding. Results indicate that binding of ACPH is through partial intercalation
      in the minor groove of DNA.

PMID- 20135311
TI  - Variation in vegetation structure and soil properties, and the relation between
      understory plants and environmental variables under different Phyllostachys
      pubescens forests in southeastern China.
AB  - Biodiversity maintenance and soil improvement are key sustainable forestry
      objectives. Research on the effects of bamboo forest management on plant
      diversity and soil properties are therefore necessary in bamboo-growing regions,
      such as southeastern China's Shunchang County, that have not been studied from
      this perspective. We analyzed the effects of different Phyllostachys pubescens
      proportions in managed forests on vegetation structure and soil properties using
      pure Cunninghamia lanceolata forests as a contrast, and analyzed the relation
      between understory plants and environmental variables (i.e., topography, stand
      and soil characteristics) by canonical correspondence analysis (CCA). The forest
      with 80% P. pubescens and 20% hardwoods (such as Phoebe bournei, Jatropha curcas,
      Schima superba) maintained the highest plant diversity and best soil properties,
      with significantly higher plant diversity than the C. lanceolata forest, and
      better soil physicochemical and biological properties. The distribution of
      understory plants is highly related to environmental factors. Silvicultural
      disturbance strongly influenced the ability of different bamboo forests to
      maintain biodiversity and soil quality under extensive management, and the forest
      responses to management were consistent with the intermediate-disturbance
      hypothesis (i.e., diversity and soil properties were best at intermediate
      disturbance levels). Our results suggest that biodiversity maintenance and soil
      improvement are important management goals for sustainable bamboo management. To
      achieve those objectives, managers should balance the inputs and outputs of
      nutrients and protect understory plants by using appropriate fertilizer (e.g.,
      organic fertilizer), adjusting stand structure, modifying utilization model and
      the harvest time, and controlling the intensity of culms and shoots harvests.

PMID- 20135312
TI  - Adhesive bowel obstruction: letter to the editor.

PMID- 20135313
TI  - Simultaneous/Incidental cholecystectomy during gastric/esophageal resection:
      systematic analysis of risks and benefits.
AB  - BACKGROUND: After esophageal/gastric resection with resulting truncal vagotomy,
      the incidence of gallstone formation seems to increase. The clinical relevance of
      gallstones and the role of simultaneous/incidental cholecystectomy in this
      setting are controversially discussed. METHODS: Systematic analysis has been
      performed for retrospective/prospective studies on the incidence/symptoms of
      gallstone formation after esophageal/gastric resection. Pooled estimates of the
      incidence of cholecystectomies were calculated by random effect models. Risk
      analyses of simultaneous, acute postoperative cholecystectomy and long-term
      cholecystectomy were performed. RESULTS: Sixteen studies on gallstone formation
      after upper gastrointestinal (GI) surgery (3,735 patients) reported increased
      incidences of 5-60% with a pooled estimate of 17.5% (95% confidence interval
      (CI), 14.1-21.2%; inconsistency statistic (I (2)) = 86%) compared with 4-12% in
      the control population. In 113 of 3,011 patients (12 studies), late
      cholecystectomies were performed for symptomatic cholecystolithiasis,
      corresponding to an estimated overall proportion of 4.7% (95% CI, 2.1-8.2%; I (2)
      = 92%). In 1.2% (95% CI, >0-3.7%; I (2) = 93%) of patients undergoing upper GI
      surgery, a cholecystectomy was performed because of acute postoperative biliary
      problems (4 studies, 8,748 patients). Simultaneous cholecystectomy had a higher
      morbidity of 0.95% (95% CI, 0.54-1.49%; I (2) = 28%) compared with the calculated
      additional morbidity of early and late cholecystectomy of 0.45%. CONCLUSIONS:
      Approximately 6% of patients undergoing upper GI surgery are expected to require
      cholecystectomy during follow-up. Because late cholecystectomies can be performed
      safely and because the additional calculated morbidity for these operations is
      lower than the morbidity for simultaneous cholecystectomy, it cannot generally be
      recommended to remove a normal acalculous gallbladder during upper GI surgery.

PMID- 20135315
TI  - Surgeon-performed ultrasound in patients referred for thyroid disease improves
      patient care by minimizing performance of unnecessary procedures and optimizing
      surgical treatment.
AB  - BACKGROUND: Ultrasonography has become an indispensable tool in the evaluation of
      thyroid nodular disease, and most patients will have had a thyroid ultrasound
      prior to initial surgical evaluation. This study examines the added benefit of
      office-based, surgeon-performed ultrasonography in patients referred for thyroid
      disease. METHODS: All patients referred to a single endocrine surgeon for
      evaluation of thyroid disease over a 2-year period were reviewed. Outside
      ultrasonographic findings were compared to the surgeon-performed ultrasound that
      was used to formulate treatment decisions. RESULTS: Of 286 consecutive patients
      referred for surgical evaluation of thyroid disease, 261 had an outside
      ultrasound available for comparison. There were 239 women and 47 men. Mean age
      was 54.7 +/- 16.6. In 46 patients (17.6%), differences between the two
      ultrasounds were significant enough to alter treatment plans. For 18 patients no
      distinct nodule was identified and biopsy was avoided. Nine of these patients had
      ultrasound characteristics of Hashimoto's disease. In five patients the nodule
      was significantly smaller than reported and biopsy was not warranted. Twelve
      patients had nonpalpable, enlarged lymph nodes not previously identified; these
      were biopsied. Three were positive for metastatic thyroid cancer, which prompted
      the addition of neck dissection to the operative procedure. In 8 of 132 patients
      undergoing thyroidectomy, the surgical procedure was significantly altered by the
      ultrasound findings. CONCLUSIONS: This study demonstrates a clear advantage for
      patients who undergo a surgeon-performed ultrasound. For many, unnecessary
      procedures were prevented. For others, substantial modifications to the extent of
      surgery were made when new ultrasonographic findings were identified during the
      preoperative investigation.

PMID- 20135316
TI  - Choledochoduodenostomy as an alternative to choledochojejunostomy for biliary
      reconstruction in liver transplantation.

PMID- 20135317
TI  - Alterations in the interaction between GAL4 and GAL80 effect regulation of the
      yeast GAL regulon mediated by the F box protein Dsg1.
AB  - The interplay between the yeast prototypical transcriptional activator Gal4p and
      the inhibitor protein Gal80p determines the transcriptional status of the genes
      needed for galactose utilization in Saccharomyces cerevisiae. In this study, we
      showed that deletion of dsg1 coding for the F box protein Dsg1/Mdm30 delayed but
      did not eliminate growth of yeast on galactose. Correspondingly, the impaired
      expression of a GAL1-LacZ reporter in the absence of Dsg1 was only apparent
      during an early stage of induction. The requirement for Dsg1 in induction was
      abrogated by the absence of Gal80p or partly bypassed by Gal4 derivatives with
      decreased interaction with Gal80p. A K23R mutation in the DNA-binding domain of
      Gal4p was also identified to alleviate the induction defect by dsg1 deletion. On
      the other hand, the overall accumulation of multi-ubiquitylated Gal4p was not
      affected by the absence of dsg1 and the induction defect with deletion of dsg1
      was partly rescued by disruption of dnm1, a gene encoding a component of the
      mitochondria division machinery. Taken together, these results suggest that the
      Dsg1-mediated efficient transcription process of GAL genes may depend on the
      interaction status between Gal4p and Gal80p.

PMID- 20135318
TI  - Bombyx mori nucleopolyhedrovirus ORF94, a novel late protein is identified to be
      a component of ODV structural protein.
AB  - Orf94 (Bm94) of Bombyx mori nucleopolyhedrovirus (BmNPV) potentially encodes 424
      amino acids with a predicted molecular weight of 49.4 kDa, but its function
      remains unknown. Blast search results revealed that Bm94 homologues exist in 10
      completely sequenced Lepidopteron NPVs with identities ranging from 95 to 37%.
      Results of our recent study showed that Bm94 was transcribed from 12 to 72 h and
      the corresponding protein was detected from 24 to 72 h post-infection.
      Furthermore, Western blot analysis revealed that Bm94 was present in occlusion
      derived virus (ODV) and in total protein from BmNPV-infected BmN cells, but not
      in budded virus. Immunofluorescence analysis revealed that the protein located
      primarily in the cytoplasm and was also present in the nucleus in the later
      infection. In conclusion, these results together indicated that Bm94 was a late
      gene, which distributed both in the cytoplasm and in the nucleus, and was
      identified to be a component of BmNPV ODV.

PMID- 20135319
TI  - Biosurfactant production by halotolerant Rhodococcus fascians from Casey Station,
      Wilkes Land, Antarctica.
AB  - Isolate A-3 from Antarctic soil in Casey Station, Wilkes Land, was characterized
      for growth on hydrocarbons. Use of glucose or kerosene as a sole carbon source in
      the culture medium favoured biosynthesis of surfactant which, by thin-layer
      chromatography, indicated the formation of a rhamnose-containing glycolipid. This
      compound lowered the surface tension at the air/water interface to 27 mN/m as
      well as inhibited the growth of B. subtilis ATCC 6633 and exhibited hemolytic
      activity. A highly hydrophobic surface of the cells suggests that uptake occurs
      via a direct cell-hydrocarbon substrate contact. Strain A-3 is Gram-positive,
      halotolerant, catalase positive, urease negative and has rod-coccus shape. Its
      cell walls contained meso-diaminopimelic acid. Phylogenetic analysis based on
      comparative analysis of 16S rRNA gene sequences revealed that strain A-3 is
      closely related to Rhodococcus fascians with which it shares 100% sequence
      similarity. This is the first report on rhamnose-containing biosurfactant
      production by Rhodococcus fascians isolated from Antarctic soil.

PMID- 20135320
TI  - Assessing the prospects of genome-wide association studies performed in inbred
      mice.
AB  - The remarkable success in mapping genes linked to a number of disease traits
      using genome-wide association studies (GWAS) in human cohorts has renewed
      interest in applying this same technique in model organisms such as inbred
      laboratory mice. Unlike humans, however, the limited genetic diversity in the
      ancestry of laboratory mice combined with selection pressure over the past
      decades have yielded an intricate population genetic structure that can
      complicate the results obtained from association studies. This problem is further
      exacerbated by the small number of strains typically used in such studies where
      multiple spurious associations arise as a result of random chance. We sought to
      empirically assess the viability of GWAS in inbred mice using hundreds of
      expression traits for which the true location of the expression quantitative
      trait locus was known a priori. We then measured transcript abundance levels for
      these expression traits in 16 classical and 3 wild-derived inbred strains and
      carried out a genome-wide association scan, demonstrating the low statistical
      power of such studies and empirically estimating the large extent to which
      allelic association of transcripts gives rise to spurious associations. We
      provide evidence illustrating that in a large fraction of cases, the marker with
      the most significant p values fails to map to the location of the true eQTL.
      Finally, we provide experimental support for hundreds of traits, and that
      combining linkage analysis with association mapping provides significant
      increases in statistical power over a stand-alone GWAS as well as significantly
      higher mapping resolution than either study alone.

PMID- 20135321
TI  - Carcinoma obstruction of the proximal colon cancer and long-term prognosis-
      obstruction is a predictor of worse outcome in TNM stage II tumor.
AB  - PURPOSE: Colon obstruction is suggested to be a predictor of poor outcome in
      colon cancer. However, the effect of obstruction on outcome in patients with
      different tumor-nodes-metastases (TNM) stage cancer has not been fully addressed.
      The aim of this study is to determine whether colon obstruction predicts surgical
      and long-term oncologic outcomes in patients with proximal colon cancer. METHODS:
      A total of 1,492 consecutive patients underwent open resection of primary
      adenocarcinoma of right colon in a single institution between January 1995 and
      December 2005. Clinical and follow-up data were extracted from a prospective
      colorectal cancer database. Univariate and multivariate analyses were performed
      to identify colon obstruction and other predictors of surgical and oncologic
      outcomes. RESULTS: Among 1,492 patients, 306 (20.5%) patients presented with
      colon obstruction. The rates of surgical morbidity and mortality were greater in
      patients with an obstruction as compared to patients without an obstruction
      (22.2% and 3.9% vs. 14.1% and 1.9%; p = 0.0005 and 0.041, respectively).
      Obstruction predicted a worse long-term disease-free survival (DFS) among
      patients with stage II-III disease (log-rank test, p = 0.0003). The data were
      stratified by TNM stage. Obstruction predicted a worse DFS among patients with
      TNM stage II cancer (598 patients; log-rank test, p = 0.001; Cox regression, p =
      0.012), but it was not a predictor in TNM stage III cancer patients (424
      patients; p = 0.116; p = 0.108). CONCLUSIONS: Colon obstruction was an
      independent predictor of long-term outcome only in TNM stage II but not in stage
      III proximal colon cancer. Patients with TNM stage II obstructive colon cancer
      could be included in future trials of adjuvant therapies.

PMID- 20135322
TI  - Volvulus of an ileoanal J pouch.

PMID- 20135323
TI  - Petechial bleedings in sudden infant death.
AB  - The autopsy reports of 484 cases of deceased infants (201 females, 283 males)
      were analysed retrospectively for the existence of external and internal
      petechial bleedings (PET). The cases were divided into five groups on the basis
      of the cause of death (sudden infant death syndrome, sepsis, airway infections,
      asphyxia and trauma). Internal PET (pleural, pericardial, epicardial, thymic and
      peritoneal) were observed in each group with a lower prevalence in cases of
      trauma. The highest prevalence of external (cutaneous and conjunctival) PET was
      detected in cases of asphyxia (38% and 31%, respectively). However, even if with
      low prevalence, such bleedings were detected in every group. Factors like sex,
      age, cardiopulmonary resuscitation and its duration did not influence the
      presence of PET. The detection of external PET at autopsy is a suspicious finding
      that suggests asphyxia. Because of the possible natural origin of these
      bleedings, the medicolegal investigation has to be as complete as possible and
      has to include histology as mandatory.

PMID- 20135324
TI  - Over-expression of osa-MIR396c decreases salt and alkali stress tolerance.
AB  - Salt and alkali stress are two of the main environmental factors limiting rice
      production. Thus, understanding the mechanisms of salinity and alkali stress
      tolerance is necessary to modify rice to increase its resistance to salinity and
      alkaline stress. MicroRNAs (miRNAs) are approximately 21-nucleotide RNAs that are
      ubiquitous regulators of gene expression in eukaryotic organisms. In plants,
      miRNAs constitute one of five classes of small RNAs that function primarily as
      negative regulators for gene expression at the posttranscriptional level. Several
      plant miRNAs, such as miR396, play vital roles in plant growth, development and
      resistance to stresses. In this study, we identified osa-MIR396c, which shows
      dramatic transcript change under salt and alkali stress conditions in Oryza
      sativa. We designed an experiment to detect miRNA-target interaction and
      demonstrated that several transcription factors related to growth, development,
      and stress tolerance are targeted by osa-MIR396c. Transgenic rice and Arabidopsis
      thaliana plants constitutively over-expressing osa-MIR396c showed reduced salt
      and alkali stress tolerance compared to that of wild-type plants. Overall, this
      study further established a link between salt and alkali stress and osa-MIR396c
      in rice.

PMID- 20135325
TI  - Light screening in lichen cortices can be quantified by chlorophyll fluorescence
      techniques for both reflecting and absorbing pigments.
AB  - Lichens, representing mutualistic symbioses between photobionts and mycobionts,
      often accumulate high concentrations of secondary compounds synthesized by the
      fungal partner. Light screening is one function for cortical compounds being
      deposited as crystals outside fungal hyphae. These compounds can non
      destructively be extracted by 100% acetone from air-dry living thalli. Extraction
      of atranorin from Physcia aipolia changed the lichen colour from pale grey to
      green in the hydrated state, whereas acetone-rinsed and control thalli were all
      pale grey when dry. Removal of parietin from Xanthoria parietina changed the
      colour of desiccated thalli from orange to grey. Colour changes were quantified
      by reflectance measurements. By a new chlorophyll fluorescence method, screening
      was assessed as the decrease in incident irradiance (PAR) necessary to reach
      identical effective quantum yields of PSII (Phi(PSII)) in acetone-rinsed and
      control thalli. Thereby, we estimated a screening efficiency due to cortical
      atranorin crystals at 61, 38, and 40% of blue, green and red light, respectively,
      whereas parietin screened 81, 27 and 1% of these wavelength ranges. Removal of
      atranorin caused similar levels of increased photoinhibition for P. aipolia in
      blue, green and red light, whereas parietin-deficient thalli of X. parietina
      exhibited increased photoinhibition with decreasing wavelengths. Atranorin
      possibly prevents water from entering the spaces between the hyphae in the
      cortex. The air-filled cavities with white atranorin crystals reflect excess
      light, whereas the yellow compound parietin absorbs excess light. Thereby, both
      atranorin and parietin play significant photoprotective roles for symbiotic green
      algae, but with compound-specific screening mechanisms.

PMID- 20135326
TI  - Predation and infanticide influence ideal free choice by a parrot occupying
      heterogeneous tropical habitats.
AB  - The ideal free distribution (IFD) predicts that organisms will disperse to sites
      that maximize their fitness based on availability of resources. Habitat
      heterogeneity underlies resource variation and influences spatial variation in
      demography and the distribution of populations. We relate nest site productivity
      at multiple scales measured over a decade to habitat quality in a box-nesting
      population of Forpus passerinus (green-rumped parrotlets) in Venezuela to examine
      critical IFD assumptions. Variation in reproductive success at the local
      population and neighborhood scales had a much larger influence on productivity
      (fledglings per nest box per year) than nest site or female identity. Habitat
      features were reliable cues of nest site quality. Nest sites with less vegetative
      cover produced greater numbers of fledglings than sites with more cover. However,
      there was also a competitive cost to nesting in high-quality, low-vegetative
      cover nest boxes, as these sites experienced the most infanticide events. In the
      lowland local population, water depth and cover surrounding nest sites were
      related with F. passerinus productivity. Low vegetative cover and deeper water
      were associated with lower predation rates, suggesting that predation could be a
      primary factor driving habitat selection patterns. Parrotlets also demonstrated
      directional dispersal. Pairs that changed nest sites were more likely to disperse
      from poor-quality nest sites to high-quality nest sites rather than vice versa,
      and juveniles were more likely to disperse to, or remain in, the more productive
      of the two local populations. Parrotlets exhibited three characteristics
      fundamental to the IFD: habitat heterogeneity within and between local
      populations, reliable habitat cues to productivity, and active dispersal to sites
      of higher fitness.

PMID- 20135327
TI  - Toward in vitro fertilization in Brachiaria spp.
AB  - Brachiaria are forage grasses widely cultivated in tropical areas. In vitro
      pollination was applied to accessions of Brachiaria spp. by placing pollen of non
      dehiscent anthers on a solid medium near isolated ovaries. Viability and in vitro
      germination were tested in order to establish good conditions for pollen
      development. Comparing sexual to apomictic plants, apomictic pollen has more
      abortion after meiosis during the microspore stage and a lower viability and, of
      both types, only some plants have sufficient germination in a high sugar
      concentration. Using in vitro pollination with the sexual plant, the pollen tube
      penetrates into the nucellus and micropyle, but the embryo sac degenerates and
      collapses. In the apomictic B. decumbens, in vitro pollination leads to the
      transfer of the sperm nuclei into the egg cell and the central cell. The results
      are discussed according to normal fertilization and barriers in sexual and
      apomictic plants.

PMID- 20135328
TI  - Anterior fusion for thoracic scoliosis.

PMID- 20135329
TI  - Lumbar spinous process split decompression.

PMID- 20135330
TI  - Correction of thoracic kyphosis with Ponte osteotomy.

PMID- 20135331
TI  - Odontoid anterior screw fixation.

PMID- 20135332
TI  - Free-hand thoracic pedicle screws placed by neurosurgery residents: a CT
      analysis.
AB  - Free-hand thoracic pedicle screw placement is becoming more prevalent within
      neurosurgery residency training programs. This technique implements anatomic
      landmarks and tactile palpation without fluoroscopy or navigation to place
      thoracic pedicle screws. Because this technique is performed by surgeons in
      training, we wished to analyze the rate at which these screws were properly
      placed by residents by retrospectively reviewing the accuracy of resident-placed
      free-hand thoracic pedicle screws using computed tomography imaging. A total of
      268 resident-placed thoracic pedicle screws was analyzed using axial computed
      tomography by an independent attending neuroradiologist. Eighty-five percent of
      the screws were completely within the pedicle and that 15% of the screws violated
      the pedicle cortex. The majority of the breaches were lateral breaches between 2
      and 4 mm (46%). There was no clinical evidence of neurovascular injury or injury
      to the esophagus. There were no re-operations for screw replacement. We concluded
      that under appropriate supervision, neurosurgery residents can safely place free
      hand thoracic pedicle screws with an acceptable breach rate.

PMID- 20135333
TI  - Predictors of outcome after decompressive lumbar surgery and instrumented
      posterolateral fusion.
AB  - There has been no agreement among different authors on guidelines to specify the
      situations in which arthrodesis is justified in terms of results, risks and
      complications. The aim of this study was to identify preoperative predictors of
      outcome after decompressive lumbar surgery and instrumented posterolateral
      fusion. A prospective observational study design was performed on 203 consecutive
      patients. Potential preoperative predictors of outcome included sociodemographic
      factors as well as variables pertaining to the preoperative clinical situation,
      diagnosis, expectations and surgery. Separate multiple linear regression models
      were used to assess the association between selected predictors and outcome
      variables, defined as the improvement after 1 year on the visual analog scale
      (VAS) for back pain, VAS for leg pain, physical component scores (PCS) of SF-36
      and Oswestry disability index (ODI). Follow-up was available for 184 patients
      (90.6%). Patients with higher educational level and optimistic preoperative
      expectations had a more favourable postoperative leg pain (VAS) and ODI. Smokers
      had less leg pain relief. Patients with better mental component score (emotional
      health) had greater ODI improvement. Less preoperative walking capacity predicted
      more leg pain relief. Patients with disc herniation had greater relief from back
      pain and more PCS and ODI improvement. More severe lumbar pain was predictive of
      less improvement on ODI and PCS. Age, sex, body mass index, analgesic use,
      surgeon, self-rated health, the number of decompressed levels and the length of
      fusion had no association with outcome. This study concludes that a higher
      educational level, optimistic expectations for improvement, the diagnosis of
      "disc herniation", less walking capacity and good emotional health may
      significantly improve clinical outcome. Smoking and more severe lumbar pain are
      predictors of worse results.

PMID- 20135334
TI  - Kyphoplasty for the treatment of incomplete osteoporotic burst fractures.
AB  - Kyphoplasty has become a standard procedure in the treatment of painful
      osteoporotic compression fractures. According to current guidelines, involvement
      of the posterior wall of the vertebral body is a relative contraindication. From
      February 2002 until January 2008, 97 patients with at least one AO classification
      A 3.1 fracture were treated by kyphoplasty. There was a structured follow-up for
      the medium-term evaluation of the patients' outcome. Ninety-seven patients (68 of
      whom were females and 29 of whom were males) with involvement of the vertebra's
      posterior margin averaging 76.1 +/- 12.36 (59-98) years were treated by
      kyphoplasty. The fractures of 75 patients were caused by falls from little
      height, 5 patients had suffered traffic accidents and in the case of 17 patients,
      no type of trauma was remembered. According to the AO classification, there were
      109 A 3.1.1 and one A3.1.3 injuries. Prior to surgery, all patients were
      neurologically without pathological findings. Seventy-nine fractures were
      accompanied by a narrowing of the spinal canal [average of 15% (10-40)]. Overall,
      134 vertebras were treated by Balloon kyphoplasty (81 x 1 segment, 22 x 2
      segments, 3 x 3 segments). In 47.4% of the patients, cement leakage was observed
      after surgery. All patients with cement extravasation, however, were clinically
      unremarkable. Using the visual analog scale, patients stated that prior to
      surgery their pain averaged 8.1, whereas after surgery it significantly decreased
      and averaged 1.6 (p < 0.001). In geriatric patients with osteoporotic vertebral
      fractures with partial inclusion of the posterior wall of the vertebral body,
      kyphoplasty is an effective procedure with few complications.

PMID- 20135335
TI  - Anterior chest wall abscess--an unusual complication of an odontogenic infection.
AB  - INTRODUCTION: A majority of odontogenic infections can be successfully managed
      with routine incision and drainage and empirical antibiotics. Sometimes an
      odontogenic infection may spread to contiguous spaces and descend along the neck
      causing significant morbidity and rarely even mortality. CASE REPORT: We report a
      case of an odontogenic infection which had an unusual spread to the anterior
      chest wall.

PMID- 20135336
TI  - Comparative effects of wavelengths of low-power laser in regeneration of sciatic
      nerve in rats following crushing lesion.
AB  - Peripheral nerves are structures that, when damaged, can result in significant
      motor and sensory disabilities. Several studies have used therapeutic resources
      with the aim of promoting early nerve regeneration, such as the use of low-power
      laser. However, this laser therapy does not represent a consensus regarding the
      methodology, thus yielding controversial conclusions. The objective of our study
      was to investigate, by functional evaluation, the comparative effects of low
      power laser (660 nm and 830 nm) on sciatic nerve regeneration following crushing
      injuries. Twenty-seven Wistar rats subjected to sciatic nerve injury were divided
      into three groups: group sham, consisting of rats undergoing simulated
      irradiation; a group consisting of rats subjected to gallium-aluminum-arsenide
      (GaAlAs) laser at 660 nm (10 J/cm(2), 30 mW and 0.06 cm(2) beam), and another one
      consisting of rats subjected to GaAlAs laser at 830 nm (10 J/cm(2), 30 mW and
      0.116 cm(2)). Laser was applied to the lesion for 21 days. A sciatic functional
      index (SFI) was used for functional evaluation prior to surgery and on days 7,
      14, and 21 after surgery. Differences in SFI were found between group 660 nm and
      the other ones at the 14th day. One can observe that laser application at 660 nm
      with the parameters and methods utilised was effective in promoting early
      functional recovery, as indicated by the SFI, over the period evaluated.

PMID- 20135337
TI  - Subcutaneous tissue flaps for hallux covering.
AB  - With the understanding of the extensive vascular supply of the subcutaneous
      tissue, of its efficacy in the protection of the anatomical structures and of its
      capability of promoting the adequate functioning of very stressed regions of the
      human body, the use of subcutaneous adipose flaps has become a valid and
      sometimes the only reasonable therapeutic weapon in the treatment of small and
      medium-sized tissue loss. Such a defect represents a common complication of great
      toe injuries and surgery. Here subcutaneous flap reconstruction is proposed for
      the treatment of dorsal and medial soft tissue losses of the hallux complicated
      with infection. Two case are reported. To the best of the authors' knowledge,
      this application has not been reported in this anatomical site so far. The
      technique might be worth knowing both for orthopedic and plastic surgeons, as it
      may represent a safe, less invasive solution for most tegumentary problems of the
      dorso-medial side of the first ray.

PMID- 20135338
TI  - Higher pretherapy and significant decrease during the first 12 months of therapy
      in serum laminin levels may associate with hepatitis B e antigen seroconversion
      in chronic hepatitis B patients treated with lamivudine.
AB  - Laminin participates in regulating immune response in addition to being a
      biomarker of liver fibrosis. Lamivudine has been shown to be able to restore
      cytotoxic T-cell response in chronic hepatitis B. In this study, fifty-two
      patients with HBeAg-positive chronic hepatitis B received lamivudine treatment
      for more than 12 months. Serum laminin levels were determined at baseline and
      during treatment and analyzed regarding treatment responses at the end of 12
      months of therapy. The results showed that laminin levels at 12 months of
      treatment in patients who lost HBeAg were significantly lower compared with
      baseline (P = 0.001). The baseline laminin levels were higher in HBeAg
      seroconversion group than those without seroconversion (P = 0.037). Compared with
      baseline, the levels of serum laminin in HBeAg seroconversion group showed
      significant decrease (P = 0.001). It is concluded that higher pretherapy and
      significant decrease during the first 12 months of therapy in laminin levels may
      associate with HBeAg seroconversion in chronic hepatitis B patients treated with
      lamivudine, indicating the possible novel information of laminin for clinical
      reference.

PMID- 20135339
TI  - Transition from octahedral to tetrahedral geometry causes the activation or
      inhibition by Znf2+ of Pseudomonas aeruginosa phosphorylcholine phosphatase.
AB  - Pseudomonas aeruginosa phosphorylcholine phosphatase (PchP) catalyzes the
      hydrolysis of phosphorylcholine, which is produced by the action of hemolytic
      phospholipase C on phosphatidylcholine or sphyngomielin, to generate choline and
      inorganic phosphate. Among divalent cations, its activity is dependent on Mg(2+)
      or Zn(2+). Mg(2+) produced identical activation at pH 5.0 and 7.4, but Zn(2+) was
      an activator at pH 5.0 and became an inhibitor at pH 7.4. At this higher pH, very
      low concentrations of Zn(2+) inhibited enzymatic activity even in the presence of
      saturating Mg(2+) concentrations. Considering experimental and theoretical
      physicochemical calculations performed by different authors, we conclude that at
      pH 5.0, Mg(2+) and Zn(2+) are hexacoordinated in an octahedral arrangement in the
      PchP active site. At pH 7.4, Mg(2+) conserves the octahedral coordination
      maintaining enzymatic activity. The inhibition produced by Zn(2+) at 7.4 is
      interpreted as a change from octahedral to tetrahedral coordination geometry
      which is produced by hydrolysis of the [Zn(2+)L(2)(-1)L(2)(0) (H(2)O)(2)]
      complex.

PMID- 20135340
TI  - Isolation and characteristics of 17beta-estradiol-degrading Bacillus spp. strains
      from activated sludge.
AB  - The natural estrogen 17beta-estradiol (E2) is a major endocrine disruptor, with
      adverse effects on wildlife and humans. The aim of this study was to isolate
      microorganisms able to effectively remove E2 from wastewater. Accordingly, five
      E2-degrading strains of bacteria were isolated from activated sludge collected
      from a wastewater treatment plant. Based on their 16S RNA gene sequences, these
      five strains belonged to the genus Bacillus. All five isolates were capable of
      converting E2 to estrone (E1), greatly reducing total estrogenic activities in
      wastewater during E2 biodegradation. However, only two strains (strain E2Y1 and
      E2Y4) were able to further transform E1, whereas it accumulated in the culture
      medium of the other isolates. Among all isolates, strain E2Y4, with 100% of the
      1,400 bp 16S RNA gene matched that of B. subtilis CICC10075, exhibited the
      highest E2 and E1 degradation capacities, degrading 1 mg E2/l completely within 4
      days and further transforming 40% of the metabolite E1. Furthermore, the E2
      degradation rates of strain E2Y4 increased with increasing initial concentrations
      of the steroid, with a high degradation capacity maintained even at initial
      concentrations up to 50 mg/l. These results demonstrate the potential
      significance of strain E2Y4 in biological remediation applications.

PMID- 20135341
TI  - The ups and downs of gene regulation by electrical activity in skeletal muscles.
AB  - Adult skeletal muscles retain an adaptive capacity to switch between slow- and
      fast-twitch properties that are largely dependent on motoneuron activity. Our
      studies on the transcriptional regulation of the Troponin I slow (TnIs) and fast
      (TnIf) genes uncovered a dual mechanism of transcriptional enhancement and
      repression by a single activity pattern, that promotes the phenotypic differences
      among myofibers while preserving their adaptive capacity. Using the Tnf Fast
      Intronic Regulatory Element (FIRE), we initially demonstrated that fast-patterned
      activity (infrequent, high frequency depolarization) is necessary to up-regulate
      FIRE-dependent transcription and that its effect differs dramatically from muscle
      denervation. Hence, the "fast muscle program" is not a default state mimicked
      simply by denervation or muscle inactivity. Next, we found that slow-patterned
      activity (tonic, slow frequency stimulation) selectively represses FIRE-dependent
      transcription while enhancing transcription from the TnIs Slow Upstream
      Regulatory Element. Unexpectedly, repression of the TnIf FIRE by slow-patterned
      activity is mediated by an NFAT element that directly binds NFATc1, a
      transcription factor that translocates to the nucleus selectively by slow-pattern
      depolarization and has been implicated in the up-regulation of the slow muscle
      program. Transfection of siRNAs targeting NFATc1 or mutation of the TnIFIRE NFAT
      site result in the upregulation of FIRE-dependent transcription in slow muscle,
      but have no effect in fast muscle. These findings demonstrate a novel function of
      NFAT as a repressor of transcription of fast contractile genes in slow muscles
      and, more importantly, they illustrate how specific activity patterns can enhance
      the phenotypic differences among fibre-types by differentially regulating
      transcription in a use-dependent manner while retaining the adaptive properties
      of adult muscles.

PMID- 20135343
TI  - Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk: a meta
      analysis from 41 studies with 16,480 cases and 22,388 controls.
AB  - The association between methylenetetrahydrofolate reductase (MTHFR) gene
      polymorphisms and breast cancer risk has been widely reported, but results were
      inconsistent and underpowered. To clarify the effects of MTHFR polymorphisms on
      the risk of breast cancer, an updated meta-analysis of all available studies
      relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of breast
      cancer was conducted. Eligible articles were identified by search of databases
      including MEDLINE, PubMed, Web of Science, EMBASE and Chinese Biomedical
      Literature database (CBM) for the period up to January 2010. Finally, a total of
      41 studies with 16,480 cases and 22,388 controls were included, all for C677T
      polymorphism and 20 with 12,170 cases and 15,865 controls for A1298C
      polymorphism. The pooled ORs were performed for the allele contrasts, additive
      genetic model, dominant genetic model, and recessive genetic model, respectively.
      Subgroup analyses were also performed by ethnicity and menopausal status. With
      respect to C677T polymorphism, significantly elevated breast cancer risk was
      found in overall analysis (T vs. C: OR = 1.041, 95% CI = 1.009-1.073; TT vs. CC:
      OR = 1.132, 95% CI = 1.019-1.259; TT vs. CC + CT: OR = 1.119, 95% CI = 1.014
      1.236); in the subgroup analysis by ethnicity, significantly increased risk was
      found in East Asian population (T vs. C: OR = 1.121, 95% CI = 1.016-1.237; TT vs.
      CC: OR = 1.331, 95% CI = 1.073-1.650; TT vs. CC + CT: OR = 1.265, 95% CI = 1.058
      1.513) but not in Caucasian population; in the subgroup analysis by menopausal
      status, no statistically significant association was found. With respect to
      A1298C polymorphism, no significant association with breast cancer risk was
      demonstrated in overall, ethnicity- and menopausal status-based population. It
      can be concluded that potentially functional MTHFR C677T polymorphism may play a
      low penetrance role in the development of breast cancer.

PMID- 20135342
TI  - Neonatal maternal separation alters immune, endocrine, and behavioral responses
      to acute Theiler's virus infection in adult mice.
AB  - Previous studies have established a link between adverse early life events and
      subsequent disease vulnerability. The present study assessed the long-term
      effects of neonatal maternal separation on the response to Theiler's murine
      encephalomyelitis virus infection, a model of multiple sclerosis. Balb/cJ mouse
      pups were separated from their dam for 180-min/day (180-min MS), 15-min/day (15
      min MS), or left undisturbed from postnatal days 2-14. During adolescence, mice
      were infected with Theiler's virus and sacrificed at days 14, 21, or 35 post
      infection. Prolonged 180-min MS increased viral load and delayed viral clearance
      in the spinal cords of males and females, whereas brief 15-min MS increased the
      rate of viral clearance in females. The 15-min and 180-min MS mice exhibited
      blunted corticosterone responses during infection, suggesting that reduced HPA
      sensitivity may have altered the immune response to infection. These findings
      demonstrate that early life events alter vulnerability to CNS infection later in
      life. Therefore, this model could be used to study gene-environment interactions
      that contribute to individual differences in susceptibility to infectious and
      autoimmune diseases of the CNS.

PMID- 20135345
TI  - BRCA2 N372H polymorphism and breast cancer susceptibility: a meta-analysis
      involving 44,903 subjects.
AB  - Published data on the association between BRCA2 N372H polymorphism and breast
      cancer risk are inconclusive. To derive a more precise estimation of the
      relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to
      assess the strength of association between them. A total of 22 studies including
      22,515 cases and 22,388 controls were involved in this meta-analysis. Overall, no
      significant associations were found between BRCA2 N372H polymorphism and breast
      cancer risk when all studies pooled into the meta-analysis (NH versus NN: OR =
      1.01, 95% CI = 0.97-1.05; HH versus NN: OR = 1.05, 95% CI = 0.97-1.13; dominant
      model: OR = 1.01, 95% CI = 0.98-1.05; and recessive model: OR = 1.05, 95% CI =
      0.98-1.13). In the subgroup analysis by ethnicity, still no significant
      associations were found for Caucasians, Asians, or Africans. When stratified by
      study design, statistically significantly elevated risk was found for 372H allele
      based on population-based studies (HH versus NN: OR = 1.11, 95% CI = 1.01-1.21;
      dominant model: OR = 1.05, 95% CI = 1.00-1.10; recessive model: OR = 1.09, 95% CI
      = 1.00-1.18). In conclusion, this meta-analysis suggests that the BRCA2 372H
      allele may be a low-penetrant risk factor for developing breast cancer. However,
      large sample and representative population-based studies with homogeneous breast
      cancer patients and well matched controls are warranted to confirm this finding.

PMID- 20135344
TI  - Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a
      population-based study of risk of contralateral breast cancer.
AB  - Given the greatly elevated risks of contralateral breast cancer (CBC) observed in
      breast cancer patients who carry mutations in BRCA1 and BRCA2, it is critical to
      determine the effectiveness of standard adjuvant therapies in preventing CBC in
      mutation carriers. The WECARE study is a matched, case-control study of 708 women
      with CBC as cases and 1,399 women with unilateral breast cancer (UBC) as
      controls, including 181 BRCA1/BRCA2 mutation carriers. Interviews and medical
      record reviews provided detailed information on risk factors and breast cancer
      therapy. All study participants were screened for BRCA1 and BRCA2 mutations using
      denaturing high-performance liquid chromatography (DHPLC) to detect genetic
      variants in the coding and flanking regions of the genes. Conditional logistic
      regression was used to compare the risk of CBC associated with chemotherapy and
      tamoxifen in BRCA1/BRCA2 mutation carriers and non-carriers. Chemotherapy was
      associated with lower CBC risk both in non-carriers (RR = 0.6 [95% CI: 0.5-0.7])
      and carriers (RR = 0.5 [95% CI: 0.2-1.0]; P value = 0.04). Tamoxifen was
      associated with a reduced CBC risk in non-carriers (RR = 0.7 [95% CI: 0.6-1.0]; P
      value = 0.03). We observed a similar but non-significant reduction associated
      with tamoxifen in mutation carriers (RR = 0.7 [95% CI: 0.3-1.8]). The tests of
      heterogeneity comparing carriers to non-carriers did not provide evidence for a
      difference in the associations with chemotherapy (P value = 0.51) nor with
      tamoxifen (P value = 0.15). Overall, we did not observe a difference in the
      relative risk reduction associated with adjuvant treatment between BRCA1/BRCA2
      mutation carriers and non-carriers. However, given the higher absolute CBC risk
      in mutation carriers, the potentially greater impact of adjuvant therapy in
      reducing CBC risk among mutation carriers should be considered when developing
      treatment plans for these patients.

PMID- 20135346
TI  - Metformin and rapamycin have distinct effects on the AKT pathway and
      proliferation in breast cancer cells.
AB  - Rapamycin and its analogues inhibit mTOR, which leads to decreased protein
      synthesis and decreased cancer cell proliferation in many experimental systems.
      Adenosine 5'- monophosphate-activated protein kinase (AMPK) activators such as
      metformin have similar actions, in keeping with the TSC2/1 pathway linking
      activation of AMPK to inhibition of mTOR. As mTOR inhibition by rapamycin is
      associated with attenuation of negative feedback to IRS-1, rapamycin is known to
      increase activation of AKT, which may reduce its anti-neoplastic activity. We
      observed that metformin exposure decreases AKT activation, an action opposite to
      that of rapamycin. We show that metformin (but not rapamycin) exposure leads to
      increased phosphorylation of IRS-1 at Ser(789), a site previously reported to
      inhibit downstream signaling and to be an AMPK substrate phosphorylated under
      conditions of cellular energy depletion. siRNA methods confirmed that reduction
      of AMPK levels attenuates both the IRS-1 Ser(789) phosphorylation and the
      inhibition of AKT activation associated with metformin exposure. Although both
      rapamycin and metformin inhibit mTOR (the former directly and the latter through
      AMPK signaling), our results demonstrate previously unrecognized differences
      between these agents. The data are consistent with the observation that maximal
      induction of apoptosis and inhibition of proliferation are greater for metformin
      than rapamycin.

PMID- 20135347
TI  - Epidermal growth factor receptor and vascular endothelial growth factor receptor
      2 are specific biomarkers in triple-negative breast cancer. Results from a
      controlled randomized trial with long-term follow-up.
AB  - Triple-negative breast cancer (TNB) has poor prognosis and moreover patients with
      TNB do not benefit from established targeted drugs with endocrine therapy or
      trastuzumab. The aim of the study was to analyze the prevalence of candidate
      biomarkers in tumors from patients with TNB. Tissue microarrays were prepared
      from primary tumors from premenopausal breast cancer patients (500/564)
      randomized to adjuvant tamoxifen or no adjuvant treatment. Immunohistochemical
      (IHC) staining included ER, PR, HER2, epidermal receptor growth factor (EGFR),
      vascular endothelial growth factor A (VEGF-A), and vascular endothelial growth
      factor receptor 2 (VEGFR2). EGFR and HER2 gene copy number was defined by
      fluorescence in situ hybridization (FISH). All patients were included in the
      descriptive analysis, but only untreated patients in the survival analysis. TNB
      was diagnosed in 96 patients and correlated significantly to low age, Nottingham
      histological grade (NHG) III, high Ki67-index, T2 tumors, node negativity, EGFR
      positivity, increased EGFR gene copy number and high VEGFR2 expression. TNB was
      an independent prognostic factor for decreased 5-year breast cancer specific
      survival (BCSS) (HR 2.0 (95% CI 1.1-3.6), P = 0.01), but not for 10-year BCSS.
      High VEGFR2 expression was significantly correlated to decreased BCSS in TNB
      patients. TNB was associated with decreased BCSS and clinicopathological
      characteristics of an aggressive tumor type. High VEGFR2 expression, EGFR
      expression, and EGFR gene copy number were significantly correlated to TNB,
      supporting their role as putative candidate biomarkers for selection of targeted
      therapy in TNB.

PMID- 20135348
TI  - Screening for genomic rearrangements in BRCA1 and BRCA2 genes in Czech high-risk
      breast/ovarian cancer patients: high proportion of population specific
      alterations in BRCA1 gene.
AB  - Large genomic rearrangements (LGR) represent substantial proportion of pathogenic
      mutations in the BRCA1 gene, whereas the frequency of rearrangements in the BRCA2
      gene is low in many populations. We screened for LGRs in BRCA1 and BRCA2 genes by
      multiplex ligation-dependent probe amplification (MLPA) in 521 unrelated patients
      negative for BRCA1/2 point mutations selected from 655 Czech high-risk breast
      and/or ovarian cancer patients. Besides long range PCR, a chromosome 17-specific
      oligonucleotide-based array comparative genomic hybridization (aCGH) was used for
      accurate location of deletions. We identified 14 patients carrying 8 different
      LGRs in BRCA1 that accounted for 12.3% of all pathogenic BRCA1 mutations. No LGRs
      were detected in the BRCA2 gene. In a subgroup of 239 patients from high-risk
      families, we found 12 LGRs (5.0%), whereas two LGRs were revealed in a subgroup
      of 282 non-familial cancer cases (0.7%). Five LGRs (deletion of exons 1-17, 5-10,
      13-19, 18-22 and 21-24) were novel; two LGRs (deletion of exons 5-14 and 21-22)
      belong to the already described Czech-specific mutations; one LGR (deletion of
      exons 1-2) was reported from several countries. The deletions of exons 1-17 and 5
      14, identified each in four families, represented Czech founder mutations. The
      present study indicates that screening for LGRs in BRCA1 should include patients
      from breast or ovarian cancer families as well as high-risk patients with non
      familial cancer, in particular cases with early-onset breast or ovarian cancer.
      On the contrary, our analyses do not support the need to screen for LGRs in the
      BRCA2 gene. Implementation of chromosome-specific aCGH could markedly facilitate
      the design of primers for amplification and sequence analysis of junction
      fragments, especially in deletions overlapping gene boundaries.

PMID- 20135349
TI  - PCR-based detection and eradication of mycoplasmal infections from various
      mammalian cell lines: a local experience.
AB  - A total of 200 cell lines including different human, monkey, mice, hamster and
      rat cell types were examined for mycoplasma infection status. PCR assay using
      generic-specific universal primers showed that 40 (20%) of the cell lines are
      contaminated with mycoplasma. Employment of species-specific primers within these
      infected cell lines revealed infection with M. hyorhinis (42.5%), M. fermentas
      (37.5%), M. arginini (37.5%), M. orale (12.5%) and A. laidlawii (7.5%). A number
      of the cultures were coinfected with 2 or 3 different species. Contaminated
      samples were treated with BM-Cyclin, Ciprofloxacin and mycoplasma removal agent
      (MRA). Mycoplasma eradication was subsequently checked by PCR following 2 weeks
      continuous culture of treated cells in antibiotic free culture medium.
      Mycoplasmal infections were eradicated in 100, 70 and 42% of infected cell lines
      when the samples were treated with BM-Cyclin, MRA and Ciprofloxacin,
      respectively. However, 12% (BM-Cyclin), 62.5% (MRA) and 82.5% (Ciprofloxacin) of
      mycoplasma regrowth was observed 4 months after the treatment. Notably, the risk
      of spontaneous culture death was 17.5, 12.5 and 0% for BM-Cyclin, MRA and
      Ciprofloxacin, respectively.

PMID- 20135350
TI  - Parent and adolescent satisfaction with mental health services: does it relate to
      youth diagnosis, age, gender, or treatment outcome?
AB  - Consumer satisfaction with treatment is important information for providers of
      mental health services. The goal of the current study was to examine the
      relationship between youth and parent satisfaction ratings and the following
      youth variables: gender, age, primary diagnosis, and changes in functioning and
      symptomatology after 6 months of services. Results demonstrated that in a large
      sample of youth receiving community mental health services satisfaction with
      services differed as a function of the adolescents' clinician-derived primary
      diagnosis, age, and reported changes in symptoms and functioning. Although
      significant, these variables accounted for only a small portion of the variance
      in satisfaction. Additionally, the relationship between parent and youth ratings
      of satisfaction was low, but significant. The implications of these findings are
      discussed as well as future directions for clinicians and researchers.

PMID- 20135351
TI  - Applicability of body surface potential map in computerized optimization of
      biventricular pacing.
AB  - Biventricular pacing (BVP) could be improved by identifying the patient-specific
      optimal electrode positions. Body surface potential map (BSPM) is a non-invasive
      technique for obtaining the electrophysiology and pathology of a patient. The
      study proposes the use of BSPM as input for an automated non-invasive strategy
      based on a personalized computer model of the heart, to identify the patient
      pathology and specific optimal treatment with BVP devices. The anatomy of a
      patient suffering from left bundle branch block and myocardial infarction is
      extracted from a series of MR data sets. The clinical measurements of BSPM are
      used to parameterize the computer model of the heart to represent the individual
      pathology. Cardiac electrophysiology is simulated with ten Tusscher cell model
      and excitation propagation is calculated with adaptive cellular automaton, at
      physiological and pathological conduction levels. The optimal electrode
      configurations are identified by evaluating the QRS error between healthy and
      pathology case with/without pacing. Afterwards, the simulated ECGs for optimal
      pacing are compared to the post-implantation clinically measured ECGs. Both
      simulation and clinical optimization methods identified the right ventricular
      (RV) apex and the LV posterolateral regions as being the optimal electrode
      configuration for the patient. The QRS duration is reduced both in measured and
      simulated ECG after implantation with 20 and 14%, respectively. The optimized
      electrode positions found by simulation are comparable to the ones used in
      hospital. The similarity in QRS duration reduction between measured and simulated
      ECG signals indicates the success of the method. The computer model presented in
      this work is a suitable tool to investigate individual pathologies. The
      personalized model could assist therapy planning of BVP in patients with
      congestive heart failure. The proposed method could be used as prototype for
      further clinically oriented investigations of computerized optimization of
      biventricular pacing.

PMID- 20135352
TI  - Development of an image-based network model of retinal vasculature.
AB  - The paper presents an image-based network model of retinal vasculature taking
      account of the 3D vascular distribution of the retina. Mouse retinas were
      prepared using flat-mount technique and vascular images were obtained using
      confocal microscopy. The vascular morphometric information obtained from confocal
      images was used for the model development. The network model developed directly
      represents the vascular geometry of all the large vessels of the arteriolar and
      venular trees and models the capillaries using uniformly distributed meshes. The
      vasculatures in different layers of the retina, namely the superficial,
      intermediate, and deep layer, were modeled separately in the network and were
      linked through connecting vessels. The branching data of the vasculatures was
      recorded using the method of connectivity matrix of network (the graph theory).
      Such an approach is able to take into account the detailed vasculature of
      individual retinas concerned. Using the network model developed, a circulation
      analysis based on Poiseuille's equation was carried out. The investigations
      produced predictions of spatial distribution of the pressure, flow, and wall
      shear stress in the entire retinal vasculature. The method developed can be used
      as a tool for continuous monitoring of the retinal circulation for clinical
      assessments as well as experimental studies.

PMID- 20135353
TI  - High-shear stress sensitizes platelets to subsequent low-shear conditions.
AB  - Individuals with mechanical heart valve implants are plagued by flow-induced
      thromboembolic complications, which are undoubtedly caused by platelet
      activation. Flow fields in or around the affected regions involve brief exposure
      to pathologically high-shear stresses on the order of 100 to 1000 dyne/cm(2).
      Although high shear is known to activate platelets directly, their subsequent
      behavior is not known. We hypothesize that the post-high-shear activation
      behavior of platelets is particularly relevant in understanding the increased
      thrombotic risk associated with blood-recirculating prosthetic cardiovascular
      devices. Purified platelets were exposed to brief (5-40 s) periods of high-shear
      stress, and then exposed to longer periods (15-60 min) of low shear. Their
      activation state was measured using a prothrombinase-based assay. Platelets
      briefly exposed to an initial high-shear stress (e.g., 60 dyne/cm(2) for 40 s)
      activate a little, but this study shows that they are now sensitized, and when
      exposed to subsequent low shear stress, they activate at least 20-fold faster
      than platelets not initially exposed to high shear. The results show that
      platelets in vitro exposed beyond a threshold of high-shear stress are primed for
      subsequent activation under normal cardiovascular circulation conditions, and
      they do not recover from the initial high-shear insult.

PMID- 20135354
TI  - Pan-azole-resistant Candida guilliermondii from a leukemia patient's silent
      funguria.
AB  - Isolation of Candida non-albicans yeasts as commensals or pathogens from
      hospitalised hosts is acquiring increasing importance, due to the frequent drug
      resistance expressed by such organisms.Particularly, the recover of antifungal
      resistant C. guilliermondii is of worrisome concern, even if recovered as a
      saprophyte, since commensal yeasts may behave as reservoirs for resistance
      elements;furthermore, they may enter the bloodstream after chemotherapy-related
      mucosal damage has developed,thus causing life-threatening and difficult-to-treat
      fungemias. This communication deals with the unusual isolation of a pan-azole
      resistant C. guilliermondii strain from a leukaemic patient with silent
      candiduria and emphasizes the importance of monitoring less recurring species
      within the nosocomial setting to better understand fungal epidemiology within the
      wards and face the spread of resistance determinants. Also, we highlight the
      controversial significance of silent candiduria, clinical relevance of which
      should be investigated case by case, to exclude and/or prevent candiduria as well
      as renal impairment.

PMID- 20135355
TI  - Clinicopathological prognostic factors after hepatectomy for patients with mass
      forming type intrahepatic cholangiocarcinoma: relevance of the lymphatic invasion
      index.
AB  - BACKGROUND: The present study was conducted to clarify the pathological factors
      in patients who underwent surgery for mass-forming type intrahepatic
      cholangiocarcinoma (IHC). METHODS: From 1982 to July 2004, a total of 60 liver
      resections for mass-forming type IHC were performed at Kyushu University and its
      affiliated institutions. Portal venous, lymphatic, hepatic venous, and serosal
      invasion was examined by univariate and multivariate analyses for their
      prognostic value. The portal venous (PV) invasion index was defined as follows:
      PV0, portal venous invasion (-) and intrahepatic metastasis (-); PV1, portal
      venous invasion (+) or intrahepatic metastasis (+); PV2, portal venous invasion
      (+) and intrahepatic metastasis (+). The lymphatic invasion (LI) index was
      defined as follows: LI0, lymphatic duct invasion (-) and lymph node metastasis (
      ); LI1, intrahepatic lymphatic duct invasion (+) or lymph node metastasis (+);
      LI2, intrahepatic lymphatic duct invasion (+) and lymph node metastasis (+).
      RESULTS: In univariate analysis, statistically significant prognostic factors for
      poor outcome were tumor size (>5 cm), serosal invasion (+), PV1 or PV2, LI1 or
      LI2, histological grade (moderate and poor), hepatic venous invasion (+) and
      noncurative resection. After multivariate analysis, the lymphatic invasion index
      and histological grade were statistically independent prognostic factors for
      overall survival and recurrence-free survival. CONCLUSIONS: In patients with mass
      forming type IHC, lymphatic invasion is the most important invasion pathway,
      compared with serosal and portal and hepatic venous invasion. Stratification of
      the lymphatic invasion pathway by lymphatic invasion, including intrahepatic
      lymphatic duct invasion and lymph node metastasis, is a good predictor for
      prognosis in patients after hepatectomy for mass-forming type IHC.

PMID- 20135356
TI  - Changes in circulating tumor cell detection in patients with localized breast
      cancer before and after surgery.
AB  - BACKGROUND: Few data exist on the potential role of circulating tumor cells
      (CTCs) in patients with operable breast cancer. If the presence of CTCs in early
      breast cancer could predict an increased risk for relapse, it might be an early
      marker for treatment efficacy and could help in deciding treatment continuation.
      METHODS: Thirty milliliters of peripheral blood was taken from 56 breast cancer
      patients before surgery and again 5 days after surgery, and the presence of CTCs
      was evaluated. In case of positivity of one of the perioperative samples, another
      sample was taken after 30 days. The presence of CTCs was assessed with the
      CellSearch System (Veridex, Warren, NJ). RESULTS: One to three CTCs were found in
      16 (29%) of 56 patients before surgery, in 14 (30%) of 47 patients at day 5, and
      in 8 (30%) of 27 at day 30. No association with pathological characteristics was
      found, apart a borderline significant association between presence of CTCs at
      baseline and vascular invasion (P = 0.07). When we looked at concordance between
      CTCs at baseline and after day 5 (47 patients), we found 40% discordant samples
      (10 negative at baseline and positive at day 5, and 9 vice versa). CONCLUSIONS:
      This study provides evidence of the presence of CTCs in approximately 30% of
      patients with localized breast cancer both before and after surgery, with change
      from positive to negative and vice versa in 40% of cases. No association with the
      pathological variables was found, except for vascular invasion and presence of
      preoperative CTCs. Long-term follow-up will be required to understand the
      significance of these data.

PMID- 20135357
TI  - Outcome analysis of patients with pN2 oral cavity cancer.
AB  - BACKGROUND: The American Joint Committee on Cancer staging system suggests that
      squamous-cell carcinoma of the oral cavity (OSCC) with pN2 should be classified
      as stage IVA. The objective of the current study was to determine the outcome of
      patients with pN2 OSCC cancer according to different T status. METHODS: Between
      January 1996 and September 2007, a total of 270 patients with pN2 OSCC cancer
      were analyzed. All participants had a follow-up of at least 2 years or were
      censored on the date of last follow-up. The outcome measures for this study were
      the 5-year rates of locoregional control, distant metastases, and survival.
      RESULTS: Five-year disease-specific survival and overall survival rates in pT1 (n
      = 9), pT2 (n = 98), pT3 (n = 70), and pT4 (n = 93) patients were 78%, 66%, 49%,
      35% (P = 0.0031), and 78%, 52%, 35%, 23% (P = 0.0001), respectively.
      Multivariable analysis revealed that pT3-4, level IV/V metastases, extracapsular
      spread, and poor differentiation were independent risk factors for 5-year disease
      specific survival in the entire study cohort. Specific independent prognostic
      factors for 5-year disease-specific survival according to T stage were found.
      CONCLUSIONS: The results of this study suggest that patients with pN2 OSCC cancer
      have different outcomes and prognostic factors according to their T status. In
      the light of these findings, treatment strategies may be quite different.

PMID- 20135358
TI  - Side populations of glioblastoma cells are less sensitive to HSV-TK/GCV suicide
      gene therapy system than the non-side population.
AB  - Side populations of glioblastoma cells are resistant to chemotherapy basically
      due to ABCG2-mediated efflux of small-molecule drugs. The herpes simplex virus
      thymidine kinase/ganciclovir suicide gene therapy system is one of the best
      characterized strategies for malignant tumors including glioblastoma. Since this
      system involves a small-molecule drug ganciclovir, we wonder if glioblastoma side
      population cells are able to "pump out" ganciclovir and thus resistant to this
      suicide gene therapy. By 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)
      2-(4-sulfophenyl)-2H-tetrazolium assay, we found that side populations are more
      resistant to this system than non-side populations. By flow cytometry and
      competition assay, we found that ganciclovir is a substrate for ABCG2.

PMID- 20135359
TI  - Epithelial-mesenchymal transition in rhesus monkey embryonic stem cell colonies:
      the role of culturing conditions.
AB  - Colonies of rhesus monkey embryonic stem cells (rhESC; cell line R366.4) have
      been described before to show a spatially ordered process of epithelial
      mesenchymal transition in vitro. In the present investigations, we have studied
      variables of culturing conditions which influence the reproducibility of the
      formation of crater-like ingression centers in the colonies. Critical parameters
      are found to be age and density of mouse embryonic fibroblast (MEF) feeder cell
      layers, the mode of mitotic inactivation of the MEFs (mitomycin C, or
      irradiation), and the mode of rhESC isolation during subculturing
      (enzymatic/mechanical cell cluster isolation; type of enzyme). The described
      culturing system appears to offer a reproducible in vitro model potentially
      useful for studies on cellular processes involved in gastrulation in the primate.

PMID- 20135360
TI  - Parasiticidal activity of human alpha-defensin-5 against Toxoplasma gondii.
AB  - Human defensins play a fundamental role in the initiation of innate immune
      responses to some microbial pathogens. In this paper, we show that human alpha
      defensin-5 displays a parasiticidal role against Toxoplasma gondii, the causative
      agent of toxoplasmosis. Exposure of the tachyzoite form of T. gondii to defensin
      induced aggregation and significantly reduced parasite viability in a
      concentration-dependent peptide. Pre-incubation of tachyzoites with human alpha
      defensin-5 followed by exposure to a mouse embryonal cell line (NIH/3T3)
      significantly reduced T. gondii infection in these cells. Thus, human alpha
      defensin-5 is an innate immune molecule that causes severe toxocity to T. gondii
      and plays an important role in reducing cellular infection. This is the first
      report showing that human alpha-defensin-5 causes aggregation, leading to
      Toxoplasma destruction.

PMID- 20135361
TI  - Implication of p16 inactivation in tumorigenic activity of respiratory epithelial
      cell lines and adenocarcinoma cell line established from plutonium-induced lung
      tumor in rat.
AB  - To investigate whether p16 inactivation is involved in the development of rat
      pulmonary tumors, we compared the p16 status and tumorigenicity of cell lines
      which indicated different p16 status. The tumor cell line (PuD2) was established
      from lung adenocarcinoma induced in plutonium dioxide-inhaled rat in this study.
      The virus-immortalized SV40T2 cells, benzo[a]pyrene-induced BP cells, BP-derived
      BP(P)Tu cells, and gamma ray-transformed RTiv3 cells were utilized as the
      respiratory epithelial cell lines. A tumorigenicity assay-inoculating cells into
      nude mice revealed that PuD2, BP, and BP(P)Tu cells were tumorigenic, but SV40T2
      and RTiv3 cells were not. Methylation-specific PCR of the p16 promoter region
      revealed that SV40T2 cells were unmethylated, BP cells displayed heterogeneous
      methylation, and BP(P)Tu and RTiv3 cells were completely methylated. Methylation
      specific PCR and PCR of genomic DNA in the p16 region did not amplify product in
      PuD2 cells, indicating deletion of p16. Banded karyotypes prepared from PuD2
      cells exhibited trisomy of chromosome 4, inversion in chromosome 11, and partial
      deletion of chromosomes 4 and 5. The demethylating agent 5Aza2dC partially
      demethylated the p16 promoter region of BP(P)Tu, BP and RTiv3 cells, increasing
      expression of the p16 transcript and decreasing growth of the cells. These
      results indicate that hypermethylation of the p16 promoter region occurs early in
      neoplastic transformation before acquisition of tumorigenicity in rat respiratory
      epithelium. Loss of genes located on chromosomes 4 and 5 may be important for
      tumor progression and acquisition of high tumorigenic activity in the Pu-induced
      rat lung tumor.

PMID- 20135362
TI  - Systemic glucose and brain energy metabolism after subarachnoid hemorrhage.
AB  - BACKGROUND: Brain energy metabolic crisis (MC) and lactate-pyruvate ratio (LPR)
      elevations have been linked to poor outcome in comatose patients. We sought to
      determine if MC and LPR elevations after subarachnoid hemorrhage (SAH) are
      associated with acute reductions in serum glucose. METHODS: Twenty-eight
      consecutive comatose SAH patients that underwent multimodality monitoring with
      intracranial pressure and microdialysis were studied. MC was defined as
      lactate/pyruvate ratio (LPR) > or = 40 and brain glucose < 0.7 mmol/l. Time
      series data were analyzed using a multivariable general linear model with a
      logistic link function for dichotomized outcomes. RESULTS: Multimodality
      monitoring included 3,178 h of observation (mean 114 +/- 65 h per patient). In
      exploratory analysis, serum glucose significantly decreased from 8.2 +/- 1.8
      mmol/l (148 mg/dl) 2 h before to 6.9 +/- 1.9 mmol/l (124 mg/dl) at the onset of
      MC (P < 0.001). Reductions in serum glucose of 25% or more were significantly
      associated with new onset MC (adjusted odds ratio [OR] 3.6, 95% confidence
      interval [CI] 2.2-6.0). Acute reductions in serum glucose of 25% or more were
      also significantly associated with an LPR rise of 25% or more (adjusted OR 1.6,
      95% CI 1.1-2.4). All analyses were adjusted for significant covariates including
      Glasgow Coma Scale and cerebral perfusion pressure. CONCLUSIONS: Acute reductions
      in serum glucose, even to levels within the normal range, may be associated with
      brain energy metabolic crisis and LPR elevation in poor-grade SAH patients.

PMID- 20135363
TI  - Cancer-specific methylation in the BRCA1 promoter in sporadic breast tumours.

PMID- 20135364
TI  - Activation of JAK/STAT signal pathway predicts poor prognosis of patients with
      gliomas.
AB  - JAK/STAT pathway transmits signals from the cell membrane to the nucleus in
      response to extracellular growth factors and cytokines. Activation of this
      pathway has been found in certain types of human tumors. The goal of this study
      was to investigate the correlation between the JAK/STAT pathway in human gliomas
      and patients' prognosis, which currently is unknown. Western blotting analysis
      and immunohistochemical staining were performed to detect JAK-1, phosphorylated
      JAK-1, and STAT-3 expression patterns in the biopsies from 96 patients with
      primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed
      to evaluate the prognosis of patients. Western blotting analysis and
      immunohistochemical staining both indicated that the expression levels of JAK-1,
      phosphorylated JAK-1, and STAT-3 in primary glioma tissues were significantly
      higher than those in normal brain tissues (P < 0.001). Especially, the positive
      expression rates of JAK-1, phosphorylated JAK-1, and STAT-3 were significantly
      higher in patients with higher grade (P = 0.001, 0.001, and 0.002, respectively)
      and lower KPS score (P = 0.01, 0.008, and 0.01, respectively). Statistical
      analysis showed that patients with gliomas expressing JAK-1 and STAT-3 have lower
      overall survival rates relative to those not expressing these proteins. Cox multi
      factor analysis showed that KPS (P = 0.03), WHO grade (P = 0.008), JAK-1 (P =
      0.005), and STAT-3 (P = 0.006) were independent prognosis factors for human
      gliomas. These results provide convincing evidence for the first time that the
      JAK/STAT pathway may play a role in the progression of human gliomas. Its
      activated state might be a potent tool for predicting the clinical prognosis of
      patients with glioma.

PMID- 20135365
TI  - Letter to the editor: THA with the ABG I prosthesis at 15 years: excellent
      survival with minimal osteolysis.

PMID- 20135366
TI  - New therapeutic approaches for management of sport-induced muscle strains.
AB  - Muscle strains are one of the most common sports-induced injuries. Depending on
      the severity and location of the muscle strain, different treatment approaches
      can be taken. This review highlights recent trends in conservative,
      pharmacologic, and surgical approaches to the management of sports-induced muscle
      injuries as presented at a symposium held during the 93rd Annual Congress of the
      Italian Society of Orthopedics and Traumatology (SIOT) in Rome, Italy in November
      2008. Conservative approaches now include growth factor therapy and
      administration of autologous platelet-rich plasma during the early postinjury
      period; however, its use is currently considered a doping violation under the
      World Anti-Doping Agency code, therefore restricting its use to nonelite sports
      people only. Topical anti-inflammatory therapy is a promising therapeutic
      strategy, since it allows local analgesic and anti-inflammatory effects while
      minimizing systemic adverse events. As the drug delivery system is critical to
      clinical effectiveness, the advent of a new delivery system for ketoprofen via a
      new-generation plaster with a marked increase in tissue penetration and a
      clinical efficacy comparable with that of oral administration, provides a viable
      option in the treatment of single sport lesions. Surgical treatment of muscle
      lesions is less common than conservative and topical therapies and indications
      are limited to more serious injuries. Presentations from SIOT 2008 show that
      advances in our understanding of the healing process and in conservative,
      pharmacologic, and surgical treatment approaches to the management of sports
      induced muscle strains contribute to better clinical outcomes, faster healing,
      and a swifter return to normal training and activity levels.

PMID- 20135554
TI  - Patient-directed care works best with family physicians specialized in their
      care.

PMID- 20135555
TI  - AAFP/Coke Alliance.

PMID- 20135556
TI  - Health care for the homeless.

PMID- 20135557
TI  - Detection and reporting of elder abuse.

PMID- 20135558
TI  - The family doctor's pledge.

PMID- 20135559
TI  - A trial of virtual hypnosis to reduce stress and test anxiety in family medicine
      residents.

PMID- 20135560
TI  - We couldn't have done it without you!

PMID- 20135561
TI  - Precepting medical students in the era of EHRs.

PMID- 20135562
TI  - An advanced course in the basics.

PMID- 20135563
TI  - Boiler room.

PMID- 20135564
TI  - A simple question.

PMID- 20135565
TI  - Always the same story: familiar narrative structures in Oliver Sacks and Nancy
      Mairs.

PMID- 20135566
TI  - Gender disparity in women's health training at a family medicine residency
      program.
AB  - BACKGROUND AND OBJECTIVES: Women's health services are an important part of the
      practice of family medicine. Anecdotally, family medicine residents' training
      experience in certain aspects of women's health differs based on the trainees'
      gender. METHODS: We conducted 5-year retrospective evaluation of acute and
      preventive women's health encounters at one site. Total number of visits, type of
      visits, and visits by resident year were compared between male and female
      residents. We also compared mean women's health in-service examination training
      scores, by year of training, for male and female residents. RESULTS: Male
      residents cared for a total 13% of the 3,415 women's health visits while female
      residents performed 59.5% of the visits; the remainder of visits were to faculty
      and other practitioners. Female resident physicians cared for 86% of all
      preventive and 91% of all acute women's health visits performed by residents.
      Female residents also had a significantly higher mean number of women's health
      visits per resident than did male residents (63 versus 20). Female residents'
      mean score of 56.8 (95% CI=51.1--62.0) on the women's health section of the in
      service exam was significantly higher than male residents' mean score of 41.7
      (95% CI=34.9--48.5). CONCLUSIONS: This study demonstrates discrepancies by gender
      in the exposure of family medicine residents to women's health cases and their
      knowledge about women's health.

PMID- 20135567
TI  - Strategies for identifying students at risk for USMLE step 1 failure.
AB  - BACKGROUND AND OBJECTIVES: Failing Step 1 of the US Medical Licensing Examination
      (USMLE) or a delay in taking the exam can negatively affect a medical student's
      ability to match into a residency program. Unfortunately, identifying students at
      risk for failing Step 1 is challenging, but it is necessary to provide proactive
      educational support. The purpose of this study was to develop a strategy to
      identify students at risk for failing Step 1. METHODS: Using a retrospective
      study design, 256 students from the class of 2008 were eligible for the study.
      Independent variables included Medical College Admission Test (MCAT) scores and
      cumulative grades from years 1--2 of medical school. The dependent variable was
      their score on the USMLE Step 1. Variables with a significant univariate
      relationship were loaded into a series of binary logistic regression models. A
      receiver operating characteristic (ROC) curve examined the significant variables.
      RESULTS: Both year-2 standard score and the MCAT biological sciences score were
      significant as predictors of failure. The ROC curve provided a range of values
      for establishing a cutoff value for each significant variable. CONCLUSION: Using
      internal and external predictors, it is possible to identify students at risk for
      failing Step 1 of the USMLE.

PMID- 20135568
TI  - Antithyroid peroxidase antibodies in patients with high normal range thyroid
      stimulating hormone.
AB  - BACKGROUND AND OBJECTIVES: Hypothyroidism is linked to heart disease and
      decreased quality of life. Since screening guidelines for the general population
      are controversial, and physicians use clinical judgment in deciding to order
      thyroid stimulating hormone (TSH), high-normal levels of TSH pose a dilemma. This
      study's objective was to compare rates of positive anti-thyroid peroxidase
      antibodies (antiTPO) tests in persons with high-normal versus low-normal TSH
      levels. METHODS: Physicians at a publicly funded family medicine outpatient
      clinic used a standard clinical set of criteria to identify patients in need of
      TSH testing. Patients with non-thyroid diseases or conditions that affect TSH
      were excluded. A total of 143 patients over 18 years of age presented with
      symptoms necessitating TSH testing and had levels that fell between 0.36 and 5.49
      IU/ml. They were allocated into two groups: 100 patients with TSH levels between
      0.36--2.49 IU/ml (low-normal TSH ) and 43 patients with TSH levels between 2.5-
      5.49 IU/ml (high-normal TSH ), and they all had measurements of antiTPO levels.
      Primary outcomes were rates of antiTPO and demographics comparisons between the
      two groups. RESULTS: The prevalence of the antiTPO antibody in the high-normal
      group was 18.6% versus 3% in the low-normal range TSH. The antiTPO prevalence was
      higher in females than in males and had a racial predominance in Hispanics
      compared to African Americans; however, these differences were not statistically
      significant. CONCLUSIONS: AntiTPO measurement may be appropriate for patients
      with high-normal TSH to help distinguish those at risk of developing true
      hypothyroidism.

PMID- 20135569
TI  - Residents' and faculty's beliefs about the ideal clinical teacher.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to examine how
      residents and faculty in family medicine compare in their beliefs about ideal
      clinical teaching. METHODS: We studied 205 residents and 148 faculty in family
      medicine who completed the Clinical Teaching Perception Inventory (CTPI) online
      between April 2001 and July 2008. The participants ranked 28 single-word
      descriptors that characterized clinical teachers along a 7-point-scale ranging
      from "least like my ideal teacher" to "most like my ideal teacher." RESULTS: Both
      residents and faculty indicated that the ideal clinical teachers should be
      stimulating, encouraging, competent, and communicating and should not be
      conventional, cautious, or controlling. However, residents rated probing and
      innovative significantly lower than did faculty. CONCLUSIONS: Clinical faculty
      and residents in family medicine have a shared view of the ideal clinical
      teacher. However, residents and faculty differed in their ratings on the
      descriptors "Probing" and "Innovative." This difference might at least in part
      stem from where residents and faculty are located along a continuum from novice
      to mature expert.

PMID- 20135571
TI  - The impact of resident gender on educational outcomes.

PMID- 20135570
TI  - Uncertain health insurance coverage and unmet children's health care needs.
AB  - BACKGROUND AND OBJECTIVES: The State Children's Health Insurance Program (SCHIP)
      has improved insurance coverage rates. However, children's enrollment status in
      SCHIP frequently changes, which can leave families with uncertainty about their
      children's coverage status. We examined whether insurance uncertainty was
      associated with unmet health care needs. METHODS: We compared self-reported
      survey data from 2,681 low-income Oregon families to state administrative data
      and identified children with uncertain coverage. We conducted cross-sectional
      multivariate analyses using a series of logistic regression models to test the
      association between uncertain coverage and unmet health care needs. RESULTS: The
      health insurance status for 13.2% of children was uncertain. After adjustments,
      children in this uncertain "gray zone" had higher odds of reporting unmet medical
      (odds ratio [OR] =1.73; 95% confidence interval [CI]=1.07, 2.79), dental
      (OR=2.41; 95% CI=1.63, 3.56), prescription (OR=1.64, 95% CI=1.08, 2,48), and
      counseling needs (OR=3.52; 95% CI=1.56, 7.98), when compared with publicly
      insured children whose parents were certain about their enrollment status.
      CONCLUSIONS: Uncertain children's insurance coverage was associated with higher
      rates of unmet health care needs. Clinicians and educators can play a role in
      keeping patients out of insurance gray zones by (1) developing practice
      interventions to assist families in confirming enrollment and maintaining
      coverage and (2) advocating for policy changes that minimize insurance enrollment
      and retention barriers.

PMID- 20135572
TI  - Fulminant sepsis-associated encephalopathy in two children: serial neuroimaging
      findings and clinical course.
AB  - We report on two children with sepsis-associated encephalopathy. They presented
      with fulminant neurological damage on clinical, neuroimaging, and
      neurophysiological findings. At onset, both went into deep coma after status
      epilepticus, resulting in near brain death. Both patients showed diffuse brain
      edema on CT and severe brain dysfunction on electroencephalography within a day
      of onset. Brain magnetic resonance (MR) imaging of one patient on day 2 showed
      restricted diffusion in the basal ganglia and the subcortical white matter of the
      frontal and occipital lobes. Brain edema aggravated and lasted for a few months
      despite a variety of treatments. MR imaging in the chronic phase revealed
      cracking lesions extending to the cerebral white matter, the cerebellum, and the
      brainstem. MR angiography showed diminished intracranial major arteries. These
      serial neuroradiological findings suggested severe brain damage resulting from
      fulminant elevation of intracranial pressure, which mimicked "brain death" or
      "respirator brain".

PMID- 20135573
TI  - Cognitive functioning in children prenatally exposed to alcohol and psychotropic
      drugs.
AB  - Cognitive functioning was compared in 29 children diagnosed with fetal alcohol
      syndrome (FAS), 35 children with fetal alcohol effects (FAE), and 66 psychotropic
      drugs-exposed (PDE) children using Wechsler tests and the neuropsychological test
      battery NEPSY. In the FAS group, verbal IQ (VIQ=78), performance IQ (PIQ=77), and
      full scale IQ (FSIQ=75) were significantly lower as compared to the FAE and PDE
      groups. In the PDE group VIQ and FSIQ were significantly higher than in the FAE
      group. In the FAS group, processing speed (PS) was significantly lower than the
      other three factors. In the FAE group, perceptual organization (PO) was
      significantly higher, whereas PS was significantly lower than the other factors.
      In the PDE group, verbal comprehension (VC) was significantly higher than the
      other factors. Attention subscales on the NEPSY were significantly lower in all
      the three groups. Prenatal alcohol exposure affects IQ levels more than exposure
      to psychotropic drugs. Attentional problems were found in all children when
      tested with the NEPSY in all groups.

PMID- 20135574
TI  - Quantitative MR imaging and spectroscopy in congenital cytomegalovirus infection
      and periventricular leukomalacia suggests a comparable neuropathological
      substrate of the cerebral white matter lesions.
AB  - Congenital CYTOMEGALOVIRUS (CMV) infection and periventricular leukomalacia (PVL)
      both lead to static cerebral white matter lesions. In contrast to PVL, the
      neuropathologicAL substrate of these lesions in congenital CMV is not clear. By
      comparing changes in quantitative magnetic resonance (MR) parameters and MR
      spectroscopy metabolite concentrations we wanted to determine whether the nature
      of the white matter pathology in congenital CMV infection could be similar to the
      known pathology of PVL. Diffusion parameters, apparent diffusion coefficient
      (ADC) and fractional anisotropy (FA), magnetization transfer ratio (MTR) and MR
      spectroscopy concentrations were studied in white matter lesions in five patients
      with a congenital CMV infection and six patients with PVL. In both groups ADC
      values were increased, FA and MTR values were reduced, concentrations of total N
      acetylaspartate and choline-containing compounds were reduced; and MYO-inositol
      concentrations were slightly increased. No differences were found between the two
      groups, suggesting that the pathology of the white matter lesions in congenital
      CMV infections is similar to that of PVL and also characterized by axonal losses,
      lack of myelin deposition due to oligodendrocytic losses, and astrogliosis.
      Congenital CMV infection and PVL affect the cerebral white matter in the same
      developmental period when immature oligodendrocytes are particularly vulnerable.

PMID- 20135575
TI  - Macrophagic myofasciitis plus (distinct types of muscular dystrophy).
AB  - Macrophagic myofasciitis (MMF) is a well-known lesion following vaccination with
      aluminium-containing vaccines. It has abundantly been reported in adults and
      several times in children, often in single patients or in rather small cohorts.
      Only few of these published reports on children have shown distinct myopathology
      of another neuromuscular disease except for MMF. Indications for biopsy often
      were nondescript clinical features in children, such as hypotonia or delay in
      motor development but, apparently, never that of suspected MMF. Thus, in previous
      reports as well as in our two patients, encountering MMF in the biopsied tissue
      specimens was coincidental. Our two unrelated patients with MMF also had two
      separate types of muscular dystrophy, a merosinopathy and dystrophinopathy,
      showing a combination of myopathologically well-defined neuromuscular diseases,
      muscular dystrophies and MMF. Detecting such a combination of two separate
      conditions may, in the future, be rare when non-invasive techniques, e. g.,
      genetic, will have replaced muscle biopsy in ascertaining hereditary
      neuromuscular conditions, especially in children.

PMID- 20135576
TI  - Intracranial calcification after cord blood neonatal transplantation for krabbe
      disease.
AB  - Infantile-onset Krabbe disease results from a deficiency of the lysosomal enzyme
      galactocerebrosidase and leads to death from profound central and peripheral
      demyelination. Neonatal hematopoietic cell transplantation may result in near
      normal cognitive development and partial rescue of gross motor development. The
      long-term course of the disorder for treated patients seems to involve slowly
      progressive neurological impairment. We describe the detailed 3-year outcomes of
      this experimental procedure using umbilical cord blood in a prenatally-diagnosed
      newborn with Krabbe disease. Substantial perivascular calcifications and atrophy
      of the white matter developed in the first year post-transplantation. Despite
      persistent neuroradiological and electrophysiological evidence of leukodystrophy,
      at age 3 years she has had only mildly impaired non-motor development and
      moderately impaired motor skills. The cause of these severe white matter changes
      may have been due to ongoing Krabbe disease or to effects of the chemotherapy
      regimen or to an interaction of these factors. Extended long-term follow-up of
      children neonatally transplanted for Krabbe disease is needed before the full
      utility and limitations of neonatal transplantation can be determined.

PMID- 20135577
TI  - Prefrontal lobe growth in a patient with continuous spike-waves during slow
      sleep.
AB  - Epilepsy with continuous spike-waves during slow sleep (CSWS) is characterized by
      impairment of neuropsychological abilities, frequently associated with behavioral
      d isorders. These manifestations strongly correlate with frontal lobe
      dysfunctions. In the present case, an 11-year-old girl presented with progressive
      behavioral deteriorations after the appearance of electrical status epilepticus
      in sleep. The duration of CSWS period was 5 months. Serial measurements (at the
      appearance of the EEG pattern, and 6 months and 1, 2, 3 and 4 years thereafter)
      of frontal and prefrontal lobe volumes by 3-dimensional magnetic resonance
      imaging-based volumetry showed growth disturbance of prefrontal lobe volume,
      particularly prefrontal-to-frontal lobe volume ratio, after the appearance of the
      EEG pattern when compared with two frontal lobe epilepsy subjects without
      neuropsychological disorders and 13 control subjects. However, the ratio was
      restored to the growth ratio and seen to reach control levels, after improvement
      of the clinical manifestations of CSWS. These results suggest that children with
      CSWS may be prone to frontal lobe dysfunctions, and that the duration of CSWS
      period seems to be a significant prognostic factor. The urgent suppression of
      this EEG abnormality may be necessary to prevent the progression of
      neuropsychological impairments.

PMID- 20135578
TI  - Atypical presentations of subacute sclerosing panencephalitis in two
      neurologically handicapped cases.
AB  - Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disorder caused
      by persistent measles infection. Here, we report two neurologically handicapped
      cases presenting with atypical features of SSPE. Patient 1 who had mild mental
      retardation manifested acute encephalopathy with partial seizures and hemiplegia,
      mimicking encephalitis. He showed a fulminant course without myoclonia or a
      periodic electroencephalogram complex. Although SSPE is usually associated with
      an increased diffusion pattern, diffusion-weighted imaging of our patient showed
      decreased diffusion in the right hippocampus. Patient 2 with infantile
      hemiparesis presented with secondary generalized seizures, followed by
      asymettrical myoclonias involving the side contralateral to the hemiparesis. A
      periodic electroencephalogram complex was absent on the previously damaged brain
      regions. Our findings show that preexisting neurological disorders may modify the
      clinical or electrophysiological findings of SSPE, leading to atypical
      presentations. SSPE should be considered in the differential diagnosis of acute
      encephalopathy with lateralizing signs or unidentified seizures. Decreased
      diffusion resolution in diffusion-weighted-imaging may correlate with rapid
      clinical progression in SSPE.

PMID- 20135579
TI  - Efficacy of continuous acyclovir infusion in neonatal herpes virus encephalitis.
AB  - We have successfully eliminated herpes simplex virus-2 from the central nervous
      system in a case of neonatal herpes simplex virus encephalitis with a continuous
      acyclovir infusion. A male infant delivered from a healthy 22-year-old woman
      without genital or systemic herpes symptoms around delivery began to develop
      fever and intractable seizures. He was started on intermittent intravenous
      acyclovir (20 mg/kg every 8 h) based on the diagnosis of herpes encephalitis. The
      virus was not eliminated with intermittent acyclovir and vidarabine, while
      continuous acyclovir was ultimately effective in eliminating herpes simplex virus
      from his central nervous system. This report demonstrates the efficacy of
      continuous acyclovir infusion in neonatal herpes simplex virus encephalitis.

PMID- 20135580
TI  - Postural headache in marfan syndrome associated with spinal cysts and liquor
      hypotension.
AB  - We here report a 13-year-old Marfan patient who suffered from severe, medication
      resistant, intermittent headache, which was provoked when getting into an upright
      position and immediately relieved by lying down or after intravenous rehydration.
      The postural benefit and the sudden relief after intravenous hydration suggested
      (intermittent) intracranial hypotension, although a normal opening pressure on
      lumbar punction was observed and no cerebrospinal fluid (CSF) leakage was
      identified. Imaging studies revealed severe dural ectasia at lumbosacral level,
      and two intradural cysts and two extradural presacral cysts were detected. Most
      likely, altered hydrodynamics in intra- and extracranial spinal meningeal cysts
      caused intermittent CSF hypotension above these cysts, resulting in intermittent
      intracranial hypotension. Surgical marsupialisation of the intradural cysts
      proved to be effective. This resulted in a significant reduction of the headache
      during the clinical follow-up of eight years.

PMID- 20135581
TI  - Red blood cell-mimicking synthetic biomaterial particles: the new frontier of
      blood doping?

PMID- 20135583
TI  - [Cardiac insufficiency as a manifestation of obstructive sleep apnea syndrome].

PMID- 20135584
TI  - [Improvement of sensoneurinal hearing loss in a patient with Muckle-Wells
      syndrome treated with anakinra].
AB  - Muckle Wells syndrome is an autoinflammatory disease in the group of cryopyrin
      associated periodic syndromes (CAPS). We report the case of an 8 year old girl
      with MWS who presented with remitting fever, urticaria, remitting coxitis,
      osteitis, bilateral uveitis anterior, elevated levels of C-reactive protein (CRP)
      and Serum amyloid A (SAA) and progressive sensoneurinal hearing loss. After
      starting treatment with anakinra, clinical symptoms dissolved almost completely
      for about two years now. CRP and SAA levels normalized quickly and sustained and
      as a consequence the risk of amyloidosis may be minimized. Notable is the
      complete recovery from sensoneurinal hearing loss merely two months after start
      of treatment. This brings up questions about pathophysiology of sensoneurinal
      hearing loss in MWS and emphasizes the benefits of an early diagnosis, as an
      early start of treatment possibly reduces long-term damage.

PMID- 20135585
TI  - Poly-axial screw removal.
AB  - As the use of instrumentation in spinal surgery has become common, the need for
      revision surgery has increased. During revision surgery one of the most difficult
      steps is removal of poly-axial pedicle screws, especially if no suitable revision
      set is available. We describe here an easy method for poly-axial screw removal.
      Leaving or placing a small piece of rod, attached firmly by a nut, tightens the
      head of the poly-axial screw. It can no longer move freely from the distal part
      of the screw and the screw can be removed by turning it counterclockwise with a
      big clamp or needle driver, which is available in almost every surgery set.

PMID- 20135586
TI  - [Second opinions get muddled: the opinions diverge].

PMID- 20135587
TI  - [Anterior shoulder instability--the current situation].
AB  - AIM: The aim of the study was to survey the current state of the conservative and
      operative treatment of anterior shoulder instability and its rehabilitation in
      German hospitals. METHODS: A previously evaluated online questionnaire was sent
      out to all German hospitals with orthopaedic or trauma surgery departments. The
      Federal Statistical Office's hospital list was the basis for the selection of
      hospitals. The questions referred to the year 2007. The survey, including 3
      reminders, was conducted over 3 months. The questionnaire consisted of 6 response
      categories: always (100%), almost always (99-81%), predominantly (80-51%), rarely
      (50-21%), almost never (20-1%) and never (0%). RESULTS: The response rate was 41%
      and 67% of these had carried out shoulder stabilisations. In total, 99.2% of the
      67% were evaluable. The proportion of shoulder surgery was 8.4% of the total
      number of operations. Shoulder stabilisations represented 10.6% of these
      operations. A specialised shoulder department existed in 22.9%. Conservative
      treatment was carried out with an immobilisation of the arm "predominantly",
      "almost always" and "always" for internal rotation in 70.8% and in 23.4% for
      external rotation. The shoulders were "predominantly", "almost always" and
      "always" stabilised in an arthroscopic technique in 68.2% and in an open one in
      31.8% of the clinics. With 92.9%, the Bankart repair was the most common
      operation. Shoulder instability was principally treated with the arthroscopic
      technique, regardless of the care level and department and is considered the best
      surgical technique. Physiotherapy was prescribed "always" and "almost always" in
      99.3%. The rate of reluxation after conservative treatment was estimated at
      35.5%, after operative open anterior shoulder stabilisation at 9.1% and after
      arthroscopic shoulder stabilization at 10.6%. Nevertheless, 49.4% of respondents
      expected the best results after arthroscopic treatment. Participants, who mainly
      applied the arthroscopic technique, expected a lower rate of reluxation in
      comparison to other techniques (p<0.001). CONCLUSION: The operative shoulder
      stabilisation is most frequently carried out as arthroscopic Bankart repair. A
      standardised, subsequent treatment is well established.

PMID- 20135588
TI  - [Toxicity of antiseptics on chondrocytes in vitro].
AB  - AIM: Local antiseptics are commonly used for perioperative skin and wound
      disinfection and as solutions for joint lavage. Therefore, we examined if an
      intra-articular use of these antiseptics is possible by using an IN VITRO
      chondrocyte model. MATERIAL AND METHODS: Articular chondrocytes harvested from 7
      patients were cultured. After reaching 80% confluency different concentrations
      (0%, 1%, 10%, 50%, 100%) of polyhexanide, hydrogen peroxide and povidone-iodine
      were added for 5 minutes. Afterwards, the solution was removed and the
      chondrocytes were cultured for 24 hours. Subsequently the vitality and
      proliferation rate (DNA synthesis) were analysed with the WST-1 and BrdU tests.
      RESULTS: 1% povidone-iodine and 1% hydrogen peroxide solutions significantly
      (p=0.001) decreased the chondrocyte vitality as compared to our control group.
      There was no significant difference (p=0.71) after the application of 1%
      polyhexanide in the vitality ratios. A significant decrease in vitality was also
      observed after the application of 10% polyhexanide solution (p=0.001).
      Application of 1% povidone-iodine solution, 1% hydrogen peroxide solution and 10%
      polyhexanide revealed a decrease in the metabolic cell activity of 80% compared
      to our control group, whereas the activity was 65% (p=0.026) compared to the
      control group after application of 1% polyhexanide solution. CONCLUSION: Our
      results demonstrate the chondrotoxic effect of the tested antiseptic solutions in
      clinical used concentrations within short time points. Polyhexanide in a low
      concentrated solution (1%) was the antiseptic with the lowest influence on the
      vitality and the DNA synthesis of chondrocytes. Thus, this antiseptic solution
      seemed to be the best choice for intra-articular application. But overall, our
      study showed general limitations for the intra-articular use of local
      antiseptics.

PMID- 20135589
TI  - [Novel software-based and validated evaluation method for objective
      quantification of bone regeneration in experimental bone defects].
AB  - AIM: The quantification of newly formed bone in experimental defect models is a
      problem in various experimental set-ups. Several methods have been described to
      evaluate and quantify the regeneration of newly formed bone in various animal
      models. Most methods only describe the amount of regenerated tissue on a semi
      quantitative level, the results significantly depend on the subjective rating of
      the observer and such evaluation methods have not been validated in terms of
      objectivity and reliability. The aim of the present study was to introduce a
      novel evaluation method for the accurate quantification of bone regeneration on
      digital X-ray images using a freely available digital image software analysis
      programme (GIMP, GNU General Public Licence). METHODS: The method introduced here
      contains 5 steps: standardisation of size and colour, determination of range of
      interest (ROI), defining different qualities of mineralisation, pixel analysis
      with histogram function, similar to the Hondsfield index, and quantification. In
      order to evaluate the objectivity and reliability, the quantification method was
      compared to semi-quantitative scores described by Mosheiff and Werntz for inter-
      and intraobserver variability. Six observers were asked to determine bone
      regeneration in 16 X-ray images of 2 different animal models. In order to
      describe intraobserver variability, the evaluation was repeated after a period of
      4 weeks. Statistical analysis including determination of intra- and interobserver
      variability (Bland-Altman coefficient of reproduction) was performed using SAS
      software. RESULTS: For both experimental set-ups analysed in this project (rabbit
      and sheep bone defects), the objectivity was significantly higher in the GIMP
      based evaluation compared to the evaluation according to Mosheiff and Werntz
      using the Bland-Altman coefficient (rabbit: GIMP: 0.095, Mosheiff: 0.272, Werntz:
      0.283; sheep: GIMP: 0.098, Mosheiff: 0.658, Werntz: 0.668). Analogous results
      were obtained for reliability (rabbit: GIMP: 0.086, Mosheiff: 0.221, Werntz:
      0.385; sheep: GIMP: 0.102, Mosheiff: 0.339, Werntz: 0.623). CONCLUSION: This
      quantification method introduced here has proved to be a reliable and "easy-to
      use" tool in order to perform objective quantification of bone regeneration in 2
      different experimental set-ups. It offers a more detailed and quantitative way
      for precise determination of regenerated tissue and is characterised by higher
      objectivity and reliability compared to other semi-quantitative evaluation
      methods. The objectivity seems to be independent of the animal model to which the
      method is applied.

PMID- 20135590
TI  - [Prophylaxis of venous thromboembolism in orthopaedic surgery--trivial option,
      huge potential].
AB  - Venous thromboembolism (VTE) is a common, sometimes even fatal though preventable
      complication after surgical interventions, especially in orthopaedic surgery. The
      risk can be reduced by more than 50 % by mechanical means and different
      anticoagulant drugs. However, only few patients receive adequate treatment.
      Medicamentous options are limited and somewhat difficult. Most anticoagulant
      substances act indirectly, therefore their efficacy can easily be impaired. For
      some, the pharmacokinetics are quite unfavourable. Furthermore, these drugs can
      cause severe adverse reactions; and since drug therapy either needs daily
      injections or routine blood checks, its acceptance is limited even further.
      Fortunately, new substances have reached phase III and will shortly be released.
      They have a broad therapeutic index, favourable pharmacodynamics and -kinetics
      and seem to cause only few adverse events. Rivaroxaban, for example, is approved
      for orthopaedic interventions like total hip or knee replacement. Orally
      administered, it interacts directly with factor Xa. It proved to be superior
      compared to the standard therapy with Enoxaparin, has a similar risk profile and
      needs no routine blood checks. The following article gives a critical survey of
      the problem, therapeutic options, current guidelines and new possibilities.
      Hopefully, these new simplified therapy options will increase the acceptance of
      VTE prophylaxis so that the rate of fatal complications after orthopaedic
      interventions can further be reduced.

PMID- 20135591
TI  - [Dislocated midclavicular fractures in children and adolescents: who benefits
      from operative treatment?].
AB  - BACKGROUND: Displaced midclavicular fractures in children are generally treated
      non-operatively. But there is a lack of age-related data concerning the
      functional and cosmetic results following conservative treatment and patients'
      content with the treatment. PATIENTS AND METHODS: In patients with displaced
      midclavicular fractures complications and pain was evaluated in relation to
      treatment option and age. Outcome was measured with the Constant Shoulder Score,
      a client satisfaction questionnaire (ZUV-8) about the satisfaction with the
      treatment and the cosmetic result and ultrasound of both clavicles. RESULTS: A
      review of emergency room and fracture clinic records revealed 101 children and
      adolescents in whom displaced midclavicular fracture had been treated between
      1/1997 and 12/2007. The follow-up included 59 patients with 60 fractures 1-10
      years after the accident. Of those, 50 fractures were treated with a sling and 10
      by operation. All patients under the age of ten were treated conservatively and
      reached very good functional and cosmetic results. Only an eight-year-old girl
      suffered from a painful pseudarthrosis. After resection and stabilisation by
      flexible intramedullary nailing, the outcome was excellent. Patients over the age
      of ten received a conservative treatment in 28 cases and ten had an operation (K
      wires fixation n=2, elastic stable intramedullary nail n=8 in 7 patients).
      Functional outcome independent of treatment method was as good as in younger
      children, but the global and cosmetic satisfaction score was much lower. Older
      patients with a non-operative treatment suffered from more pain and were
      dissatisfied with the long immobilisation. CONCLUSION: The method of choice in
      children under the age of ten with a displaced clavicular fracture is the non
      surgical treatment supported by sufficient pain medication. Older children reach
      good results but suffer from more pain and are dissatisfied by the cosmetic
      results and immobilisation. Because of this, active older children and
      adolescents with a displaced clavicular fracture benefit from elastic stable
      intramedullary nailing.

PMID- 20135592
TI  - [Comparison of short-term results after CUP prosthesis with cemented glenoid
      components and total shoulder arthroplasty: a matched-pair analysis].
AB  - AIM: The purpose of this clinical study (matched-pair design) was to compare the
      functional short-term results obtained in patients with surface replacement of
      the humeral head and cemented glenoid prosthesis with those obtained after total
      shoulder arthroplasty. METHOD: 20 patients (average age 67.7 [43-85] years, 17
      women, three men) who received surface replacement of the humeral head with
      cemented glenoid prosthesis were matched to a control group of 20 patients
      (average age 67.55 [42-85] years, 17 women, three men) with a conventional total
      shoulder arthroplasty. Six patients were treated for osteoarthritis, two for post
      traumatic arthritis, 1 each for osteonecrosis and rheumatoid arthritis.
      Preoperative status, perioperative results and postoperative status (Constant
      score, subjective assessment, range of motion, radiographic evaluation) were
      compared in all patients and controls. RESULTS: The adjusted Constant score
      improved from a mean of 37.25% to a mean of 87.75% in the hybrid group and from a
      mean of 30.8% to a value of 87.1% in the TSA group. Regarding the relative
      improvement at 12 months compared to baseline, patients treated with hybrid
      prostheses showed a comparable benefit in the Constant score, pain reduction and
      range of motion. Only the criterion "strength" revealed a significantly better
      result in the TSA group (p = 0.025). There was one irreversible injury of the
      brachial plexus in one case and neural injuries with a full recovery in two cases
      of Hybrid prosthesis. CONCLUSIONS: The combination of humeral surface replacement
      with cemented glenoid component offers a relatively new option for the treatment
      of different pathologies at the shoulder joint which need a total joint
      substitute.The short-term results are comparable with those of conventional total
      shoulder arthroplasty. Surface replacement of the shoulder facilitates later
      revision because of less loss of bone stock. It must be considered that surface
      replacement with implantation of cemented glenoid prosthesis is a difficult
      procedure because of the exploration of the glenoid.

PMID- 20135593
TI  - [Minimally invasive repair of an impingement induced partial tear of the anterior
      Achilles tendon in a top level athlete].
AB  - AIM: A rarely described Achilles tendon lesion resulting from Haglund's disease
      and its repair is presented. METHOD: An analysis of the respective clinical
      records was carried out. RESULTS: Haglund's resection was performed from a 3 cm
      lateral transverse approach. A coincidental anterior Achilles tendon partial tear
      was repaired by transversal U-sutures. CONCLUSION: A minimally invasive repair of
      a partial tear of the anterior Achilles tendon is feasible and effective.

PMID- 20135594
TI  - [Mass sports improves proprioception and reduces valgus stress on the female knee
      joint].
AB  - AIM: ACL rupture is more common in females than in males. The injury can result
      in chondral and meniscal damage or chronic instability. Most often ACL rupture
      occurs during landing after throwing and jumping in ball sports. Many studies
      have reported on incidence, mechanism of injury and predisposing factors in
      professional athletes. In contrast, we have investigated the impact of mass
      sports on predisposing factors for the female ACL rupture. METHOD: In an
      empirical analytical study leg-axis dynamics, proprioception and foot load of 44
      women participating either in regular mass sports or in no sports were
      investigated by video analysis and on the Biodex-Stability Platform. RESULTS: Our
      study demonstrates that mass sports improves proprioception of the knee joint.
      Non-sportive subjects had an increased valgus leg axis during landing in
      comparison with mass sport participants. CONCLUSION: Here, we show to the best of
      our knowledge for the first time that moderate sports activity has a positive
      effect on predisposing factors of the female ACL rupture. We conclude that
      prevention programmes focussed on jumping and proprioception can lower the
      incidence of female ACL ruptures.

PMID- 20135595
TI  - [Biochemical analysis of the synovial fluid of the shoulder joint in patients
      with and without rotator cuff tears].
AB  - AIM: The biochemical changes associated with rotator cuff tearing are still
      unclear. The aim of this study is to assess whether concentrations of matrix
      metalloproteinase in the synovial fluid are specifically altered in shoulders
      with torn rotator cuff tendons. PATIENTS AND METHOD: Synovial fluid was extracted
      via arthroscopy in 21 patients with complete rotator cuff tears (RCTs). The
      control group was composed of 21 patients without complete tears. The catabolic
      cartilage metabolism markers MMP-1 (collagenase), MMP-3 (stromelysin1) and MMP-13
      (collagenase3) were quantified by an ELISA test and these results were then
      statistically analysed using SAS. RESULTS: The mean concentration of the 21
      samples with rotator cuff tears shows a higher concentration of MMP 3 (2601.73
      ng/mL vs. 1775.67 ng/mL) and MMP 13 (2.69 ng/mL vs. 2.35 ng/mL) as well as a
      significantly higher concentration of MMP 1 (p=0.0047) in the control group.
      CONCLUSIONS: A significant variation in the concentration of catabolic cartilage
      enzymes in the synovial fluid in patients with and without rotator cuff tears
      could not be found. Nonetheless, there is a bias for the MMP-3 and MMP-13 values,
      which makes a conductive influence in the aetiology of osteoarthritis probable.

PMID- 20135596
TI  - [Desmopressin (Minirin) in multiple trauma--a case report].
AB  - Bleeding and clotting disturbances are not uncommon in trauma patients and
      require an early and consequent therapy. Under the prevalent pathophysiological
      circumstances of hypothermia, acidosis and clotting disturbances, desmopressin
      seems to be a possible option to control diffuse bleeding. We report about 2
      trauma patients with diffuse bleeding and in whom desmopressin was used
      successfully to control bleeding from the point of view of the authors. We
      discuss the advantages and disadvantages of desmopressin in the 2 patients.

PMID- 20135597
TI  - [Elastic stable intramedullary nailing as alternative therapy for the management
      of paediatric humeral shaft fractures].
AB  - AIM: We report about our experiences with the elastic stable intramedullary
      nailing (ESIN) of traumatic humeral shaft fractures in children and adolescents.
      METHOD: Children with traumatic humerus shaft fractures who were treated by ESIN
      were included. All patients underwent clinical follow-up examinations. RESULTS:
      31 children (average age 11.4 years) with traumatic humeral shaft fractures could
      be included. There were 14 oblique, 12 transverse and 5 wedge fractures. In 5
      cases the fracture was located in the proximal third, in 22 cases in the middle
      third and in 4 cases in the distal third. After an average period of 32 months a
      follow-up-examination with the Constant-Murley score was performed. All children
      attained 100 points and all patients could take part in sports activities like
      before the accident. 30 children and their parents were very satisfied with the
      treatment success and 1 patient was satisfied. The following complications were
      seen: 1 postoperative damage of the radial nerve in a patient with secondary
      fracture dislocation (complete remission), 1 skin irritation, 1 fracture
      dislocation with axial deviation, 1 secondary dislocation of the nails after a
      second accident and 1 secondary axial deviation. CONCLUSIONS: Elastic stable
      intramedullary nailing (ESIN) of humerus shaft fractures has a low complication
      rate if attention is paid to biomechanical principles. The observed complications
      are based on mistakes concerning the indication or technical errors. The ESIN
      shows very good functional and cosmetic results. It allows an early functional
      and cast-free follow-up with a quick pain reduction. The ESIN of humeral shaft
      fractures is a minimally invasive, simple and well reproducible technique with a
      steep learning curve. Because of the excellent objective and subjective results,
      the operative stabilization of humerus shaft fractures with ESIN should be
      recommended to the patients and their parents.

PMID- 20135598
TI  - [Temporary intramedullary stabilisation of infected non-union in long bones with
      local antibiotic-impregnated cement rods: case reports].
AB  - BACKGROUND: The therapy for infected non-union is complicated and needs
      multidisciplinary action. The fixateur externe is usually used to stabilise an
      osteosynthesis temporarily or permanently. But it shows a high risk with adipose
      patients and when the bone is already damaged. That is why alternative modes of
      action have been looked for. For temporary stabilisation and simultaneous
      antibiotic therapy we have invented and now use a custom-made cement rod
      impregnated with antibiotics. METHOD: We use a plastic high-lumen thorax drainage
      tube which is filled with cement mixed with antibiotics and a K-wire. When the
      cement has set the plastic is removed. The cement rod acts as a space holder.
      After the infection has calmed down we remove the space holder and a definitive
      stabilisation with a titanium nail is performed. RESULTS: The active substance
      levels tested in the wound exudation showed results clearly above the minimum
      inhibitory concentration. Early mobilisation with sole contact was mainly
      possible.The wound dressing could be performed without problems and an additional
      stabilisation was not necessary. Clinically the infection calmed down after 3 to
      4 weeks. DISCUSSION: The therapy for infected non-union of tubular bones consists
      of the complete removal of metal, the resection of the pseudarthrosis, the
      filling of the defect and the re-osteosynthesis. Intramedullary space holders
      offer a biomechanical stabilization as an intramedullary carrier of weight with
      additional simultaneous antibiotic therapy. CONCLUSION: The use of an
      intramedullary spaceholder made of antibiotic-impregnated cement in infected non
      unions avoids the specific complications of a fixateur externe and is definitely
      more comfortable for the patient. Locally high antibiotic levels are reached, the
      treatment takes less time.

PMID- 20135599
TI  - [Influence of disc prosthesis position on segmental motion in the lumbar spine].
AB  - AIM OF THE STUDY: Total disc arthroplasty is reported to maintain segmental
      motion. From finite element studies a rather posterior and central implantation
      of the prosthesis is recommended. However, there is yet no in vitro study with
      cadaveric specimens investigating the topic of implant positioning. METHODS: Ten
      human lumbar spines were subjected to biomechanical testing. Flexion/extension
      and side-bending moments were applied from 2.5-7.5 Nm on a spine load simulator.
      First, the intact specimens were tested in 3 load cycles while motion was
      monitored with regard to the facet joints under different loads by an ultrasound
      based system. An unconstrained total disc prosthesis was then implanted in a
      central position and the different load cycles were repeated. Finally the implant
      was positioned in a decentral position with an average offset of 6.2 mm for
      repetitive data acquisition. RESULTS: Comparison of the facet joint motion in
      central and eccentric prosthesis positions resulted in the following averaged
      differences. During flexion of the lumbar spine an average difference of the
      reference point excursions of 0.38 mm was recorded on the ipsilateral facet joint
      with reference to the decentral position. For extension, the difference was 0.33
      mm on average, for right side bending a difference of 0.63 mm was recorded while
      left side bending resulted in an average difference of 0.24 mm. The deviation of
      the reference markers on the contralateral facet joint showed the following
      average differences: for flexion 0.23 mm and for extension 0.54 mm, respectively.
      For side bending right/left the differences amounted to 0.18 mm and 0.39 mm. With
      regard to segmental motion there was no statistically significant difference for
      both the ipsilateral (p = 0.0564) and the contralateral (p = 0.2593) reference
      marker. CONCLUSIONS: The comparison of the segmental motion after central and
      decentral implantation of a lumbar total disc prosthesis reveals differences that
      have, nevertheless, no statistical significance. However, for clinical use it is
      recommended to strive for a central position of the implant.

PMID- 20135600
TI  - [Management of complex intra-articular distal radius fractures with open
      reduction and internal fixation with double dorsal locking plates].
AB  - AIM: In this prospective study we have analysed the clinical outcome of complex
      distal radius fractures that were reduced by a dorsal approach and fixed with 2
      dorsal locking plates. METHODS: In the period from January 2006 to June 2008 60
      patients with a distal intra-articular instable radius fracture, who were treated
      with the above mentioned procedure, were prospectively included in this study.
      All fractures showed signs of a complex and dorsal instability. X-rays and CT
      scans were taken preoperatively. Follow-up examinations and X-rays were conducted
      after 6 weeks, 6 months and 1 year. The clinical outcome was measured with the
      aid of the disability of arm, shoulder and hand (DASH) score (0-100 points). The
      functional outcome was measured with the Gartland and Wearley score (0-21
      points). Subjective pain levels were noted with the visual analogue scale (0-10
      points). RESULTS: 60 patients were examined after 6 weeks and 6 months. 40
      patients were examined after 1 year. The average age was 56 (range: 16-78 years).
      In 36% of the cases we found an accompanying injury of the upper extremity that
      had to be treated operatively. The DASH score improved on average from 47 points
      after 6 weeks (28 points after 6 months) to 24 points after 1 year. The
      subjective pain level after 1 year was 2.4 points under stress and 1.1 points in
      relaxation. The Gartland and Wearley score showed an improvement of function of
      the wrist from 9.9 points after 6 weeks to 7.4 points after 1 year, which is
      considered a good result. In 12 cases reoperations were necessary, in 6 cases due
      to a postoperative carpal tunnel syndrome (10%) and in 1 case due to an infection
      of the wound. CONCLUSION: Dorsal instable radius fractures can be stabilised in a
      satisfactory way. It is possible to achieve good results, assuming an exact
      analysis of the fracture and of the associated injuries is performed.

PMID- 20135601
TI  - [Effective skill training by means of E-learning in orthopaedic surgery].
AB  - BACKGROUND: The effectiveness of e-learning for reporting of x-ray-findings in a
      prospective, randomized trial was tested. MATERIAL AND METHODS: Twenty advanced
      medical students were randomized into two groups. The test group practiced 4-6
      hours with the newly developed software, the control group used conventional
      learning material. Afterwards, a test was carried out including 30 pathologic x
      ray films that were randomly spread through 200 non-pathologic images. The
      required time, the number of correctly appraised images and the frequency of
      falsely suspected pathologies were recorded. In addition, we asked for an
      assessment of the own capabilities in evaluating x-ray films and of passing the
      radiology training. RESULTS: The test group showed a markedly improved efficiency
      in comparison to the control group in all parameters. The required time was 57.4%
      shorter than in the control group (p < 0.05), 18.3% more cases were evaluated
      correctly (p < 0.05). The frequency of falsely suspected pathologies decreased by
      61% (p < 0.05). There was no significant correlation of the objective abilities
      of a student with his/her self-assessment or of passing the radiology course.
      CONCLUSION: This study shows that an effective standardized training of practical
      skills by means of e-learning is feasible and reasonable.

PMID- 20135602
TI  - [Mid-term results after volar plating of distal radius fractures with a newly
      designed locking plate].
AB  - BACKGROUND: The purpose of this retrospective study was to investigate the
      clinical and radiographic results after operative treatment of dislocated distal
      radius fractures with a new self-locking volar plate system. PATIENTS AND
      METHODS: 67 patients (average age 61.4 years) with a dislocated distal radius
      fracture were treated with the ITS plate system. Clinical and radiographic
      evaluation was done with a mean follow-up of 9.3 months. RESULTS: The mean DASH
      score reached 14 points, the modified Gartland/Werley score was 6.9. There was
      one loss of reduction on radiographic evaluation, which yielded to a dorsal
      osteosynthesis. Average postoperative radial inclination was 20.5 degrees (16-29
      degrees) and the volar tilt 9.3 degrees (3-15 degrees). One plate had to be
      removed after three months because of dislocation of a malpositioned screw. There
      were no cases of infection or tendon ruptures. No patient required autograft
      bone. CONCLUSION: This new locking plate system offers an excellent option in the
      treatment of dislocated distal radius fractures, especially in osteoporotic bone
      with a dorsal comminution.

PMID- 20135604
TI  - [Monteggia lesions in children--a clinical trial].
AB  - BACKGROUND: The Monteggia lesion is a rare injury of the elbow in children. This
      lesion is defined as a shaft fracture of the ulna combined with a luxation of the
      radial head. The primary problem in this injury is the proper diagnosis because
      the misalignment of the radial head is often missed. The purpose of this study
      was to retrospectively analyse the results after Monteggia lesions in children.
      PATIENTS AND METHODS: Ten children between two and nine years of age (six boys
      and four girls) were clinically assessed using the Morrey score. They were
      treated in our department between December 1999 and October 2004. RESULTS: The
      Morrey score after 54 months (min.: 26/max.: 84) had a median value of 100 points
      with 100 being the maximum (min.: 95/max.: 100). We found two complications, a
      combined lesion of the radial and ulnar nerves which completely recovered after
      six months. In one case a k-wire dislocated, which was removed earlier.
      DISCUSSION: If the Monteggia lesion in children is correctly diagnosed and
      treated early enough, only good and very good results may be expected. After
      delayed diagnosis and treatment, the clinical results are not as good or even
      very poor.

PMID- 20135605
TI  - [Patient safety in orthopaedics: implementation and first experience with CIRS
      and team time-out].
AB  - AIM: The critical incident reporting system (CIRS)and a surgical safety checklist
      (SSC) are considered to be the most powerful and important means for patient
      safety and for avoiding surgical errors. Nevertheless, these tools are not yet
      standard in orthopaedic surgery. We have implemented CIRS and a surgical
      checklist adapted to the specific conditions in orthopaedic surgery. METHOD: In
      this article, we provide a guideline to put CIRS and SSC into practice and report
      on preliminary results one year after implementation in our department. RESULTS:
      A comprehensive statistical analysis of the reduction in surgical errors cannot
      yet be given. As a first effect after one year, an improvement in
      interdisciplinary team building, an increased sense of responsibility of each
      employee and a positive change in failure culture can be observed. CONCLUSIONS:
      SSC and reporting near mistakes enables a comprehensive failure analysis helping
      to avoid future complications and improve medical quality.

PMID- 20135606
TI  - [The significance of the acetabular labrum for hip joint stability--an
      experimental study].
AB  - AIM: Aim of our study was to create artificial labra for joint models of
      different diameters (28, 32 and 36 mm) and to measure their stability potential
      at rest (SPR). The experiment was performed under the same conditions as a
      previous one with capsulated joint models. Our target was to prove the hip
      stabilising effect of the atmospheric pressure (AP) as well as the parameters for
      joint stability and to test the function of the artificial labra. METHOD:
      Uncapsulated joint models having 28 (A), 32 (B) and 36 (C) mm diameters were
      sealed with moulded preformed silicone labra. An increasing traction force was
      applied under water on the fixed joint. Using specially designed software, the
      exerted force and the dislocation distance were simultaneously and continuously
      recorded on a computer. The SPR of the examined joint models was calculated as
      the difference between the maximal exerted force and the weight of the ball-neck
      component. RESULTS: Statistical analyses showed that SPR had mean values of 58.12
      +/- 2.23 N for the 28 mm joint model (n = 118; A), 75.66 +/- 2.75 N for the 32 mm
      model (n = 88; B) and 99.91 +/- 1.30 N for the 36 mm model (n = 82; C).
      CONCLUSION: The traction force required for dislocation agreed closely to the
      expected precalculated SPR values of 58.6 N (A), 76.4 N (B) and 96.7 N (C), which
      proves the joint stabilising effect of AP in the presence of the essential
      prerequisites (spherical ball articulating in a hemispherical socket,
      hermetically closed joint capsule and/or labrum, which contains a small amount of
      fluid and excludes air). The measured SPR was directly proportional to the square
      of the joint diameter. Indirectly, it was concluded that the dislocation work at
      rest is directly proportional to the joint diameter cubed. Consequently, the risk
      of dislocation after total hip arthroplasty (THA) can be reduced by applying
      bigger, size-adapted hip balls, whose diameter grows according to the outer
      diameter of the cup. The increasing range of motion is a favourable side-effect.
      With careful reconstruction of the capsule and insertion of an intracapsular
      drain, the risk of dislocation in the early postoperative period could be
      furtherly reduced. Theoretically, artificial labra could be a useful alternative
      to augment joint stability in THA with a high dislocation tendency instead of
      constrained liners.

PMID- 20135607
TI  - [Clinical research in orthopaedics--creation of a clinical trial unit in
      orthopaedics/trauma surgery].
AB  - AIM: The clinical trial is the link between research and medical practice and
      facilitates evidence-based therapies. There are specific difficulties to be faced
      when executing clinical trials related to surgical services (learning curve of
      the surgeon, blinding etc.). As a result, surgical randomised controlled clinical
      trials (RCT) are underrepresented in the total number of RCTs. METHOD: To make it
      easier to implement surgical RCT, the Clinical Trial Unit for Orthopaedics and
      Trauma Surgery was established. Training of the supporting physicians was reached
      by rotations in the structures of CHIR-Net, a BMBF-funded network created to
      build up a region-wide surgical research infrastructure. RESULT/CONCLUSION:
      Supported by the regional CHIR-Net Center and the regional Clinical Trial Center,
      a research institute was thus founded with the aim of contributing to a long-term
      improvement in clinical research in orthopaedics and trauma surgery.

PMID- 20135608
TI  - [Muscular trunk stability in professional and amateur volleyball players].
AB  - AIM: The aim of this study was to analyse the efficiency of muscular activity in
      the trunk stabilisation of professional volleyball players compared to a group of
      amateur hobby players. The results were compared amongst the groups as well as
      with a reference group consisting of asymptomatic individuals. The question to be
      answered was whether or not professional volleyball players possess a
      characteristic strength profile in their trunk musculature and if differences
      exist with regard to the individuals' competitive playing level. METHOD: In this
      comparative study 12 professional volleyball players (German Bundesliga) and 18
      non-professional volleyball players were analysed with regard to their isometric
      strength profile in all three planes. The reference group was provided by the
      Proxomed company, which had previously analysed healthy untrained individuals (n
      = 1045) of various age groups. RESULTS: A sports-specific profile for the
      musculature of volleyball players revealed a significant reduction in the flexion
      and rotation strength as well as a well-developed lateral flexion strength
      (highly significant when compared to the reference group). With reference to the
      level played, better strength values in flexion and lateral flexion were found
      among the professional athletes. CONCLUSIONS: Professional volleyball players
      present with a characteristic trunk musculature strength profile. A detailed
      analysis of the muscle strength of the spine as part of a sports medicine work-up
      could prove helpful in preventing injuries and overuse problems in professional
      and hobby volleyball players.

PMID- 20135609
TI  - [The bipolar cup Avantage in hip revision surgery].
AB  - BACKGROUND: Luxations in revision arthroplasty are a serious complication with an
      incidence of up to 30 percent. In particular in patients with previous operation
      and resection of bone and soft tissue, the instability increases significantly.
      The use of the bipolar revision cup Avantage has to be proven valuable to avoid
      recurrent luxation. METHODS AND PATIENTS: 27 consecutive revisions of the bipolar
      acetabular component were performed. The mean age at the time of revision was 67
      years (range 40-91 years). The mean rate of previous operations was 5.1 cases
      (range 1-14). In 11 hips (40.7%) the acetabular cup was revised, in 16 hips
      (59.3%) an additional stem revision was performed. In 10 cases the revision was
      performed by a proximal femur reconstruction, in one patient by a total femur
      reconstruction. The follow-up was short-term, at a mean of 20 months (range 13-29
      months). The clinical results were evaluated prospectively by the Harris hip
      score (HHS) and the activity score according to Sutherland (aSL). The migration
      of the cup and the change of the inclination angle were calculated
      radiographically. RESULTS: There has been one dislocation of the polyethylene
      liner in the recent follow-up, which could be treated conservatively by closed
      reduction. No patients required reoperation because of technical errors or
      loosening of the bipolar acetabular implant. The HHS improved from a mean of 40.5
      (range 7-77.4) to 66.8 points (range 17.4-89.9). The modified Sutherland score
      improved to 5.9 (range 3-9) of 10 possible points. Radiographic follow-up
      revealed neither evidence of component loosening nor migration or polyethylene
      wear. CONCLUSION: Use of this bipolar unconstrained component was successful in
      restoring stability in hip revision arthroplasty, e.g., in patients with severely
      unstable hips. It has to be observed carefully if there are any disadvantages of
      these devices because of higher polyethylene wear in the mid- or long-term follow
      up. The possible disadvantages of dissociations between the inner liner from the
      outer liner or damage of the polyethylene liner limits the indication of this
      device to serious revision cases.

PMID- 20135610
TI  - [Accuracy of rotational positioning of the femoral component using the tibial-cut
      first technique].
AB  - AIM: Problems with the patellofemoral joint are still one of the most common
      difficulties after total knee arthroplasty. One of the main reasons for these
      problems seems to be the rotatory malposition of the femoral component. We
      examined the rotation of the femoral component and the symmetry of the flexion
      gap of knee prostheses implanted using the tibial-cut-first technique. METHOD:
      The radiographs of 58 consecutive patients who underwent primary LCS total knee
      arthroplasty in 2008 were examined retrospectively. The rotation of the femoral
      component was determined intraoperatively using the femoral positioner and
      depended on the amount of tibial resection and the tension of the collateral
      ligaments. The position was then checked by means of three anatomic landmarks:
      the epicondylar axis, the posterior condyles and the Whiteside line. We used
      Kanekasu's technique for the radiographs. With this technique it was possible to
      ascertain the rotation of the femoral component after total knee arthroplasty
      easily and with a low level of radiation. It was also possible to determine the
      opening of the flexion gap. RESULTS: The radiographs showed a slight external
      rotation of the femoral component of 1.31 degrees . The opening of the flexion
      gap was increased laterally, but only by 1.5 degrees . CONCLUSION: In this study,
      determination of femoral rotation using the tibial-cut-first technique resulted
      in a slight external rotation of the femoral component. Furthermore, it is
      possible to create an almost symmetrical flexion gap with this method.

PMID- 20135611
TI  - [Actual relevance of Pauwels' classification of femoral neck fractures--a
      critical review].
AB  - AIM: The aim of this study was to evaluate the validity of Pauwels'
      classification of femoral neck fractures. METHOD: A study of literature was
      performed. RESULTS: It has never been proven that the inclination of the fracture
      plane has a prognostic relevance. A number of papers prove the contrary, there
      are no publications where Pauwels' classification has been used successfully in
      selecting treatment modalities. Pauwels' theory of fracture inclination angle has
      not been transferred into clinical practice. This discrepancy probably goes back
      to the fact that the angle cannot be determined preoperatively, that in the
      majority of femoral neck fractures the angle is within the range of 40 to 60
      degrees, that the theoretical angle variations do practically not exist, and that
      the shearing forces are reduced to an unknown amount by friction resistance due
      to the uneven fracture plane. The mechanical laws of the pseudarthrosis of the
      femoral neck cannot be extrapolated to acute fractures. CONCLUSION: The theory of
      Pauwels has apparently no clinical relevance for the majority of acute fractures,
      except for the rare transcervical fractures, and should not be considered any
      longer as a classification of acute femoral neck fractures due to the lack of
      prognostic and therapeutic relevance.

PMID- 20135612
TI  - [Cartilage damage caused by a dislocated resorbable interference screw of poly(L
      lactide) 46 months after anterior cruciate ligament reconstruction].
AB  - The case of a 44-year-old male patient is reported, who was operated 4 years
      after a cruciate ligament replacement. A nearly completely intact biodegradable
      screw was removed arthroscopically. The screw dislocated from the tibial canal
      into the joint and caused damage to the retropatellar cartilage which was treated
      by debridement and lateral release. A material analysis was done on the explanted
      screw which showed no material fault. A review of the literature reporting
      adverse events connected to biodegradable implants was carried out. Nine papers
      reporting about adverse event are cited. There seem to be three main problems:
      delayed degradation, foreign body reaction and the filling of graft tunnels with
      non-ossified tissue. Instructions for the use of biodegradable interference
      screws were requested from seven manufacturers to compare the given information
      about the degradation behaviour. The information given on the period of time
      until the screws would be completely resorbed were heterogeneous, ranging from no
      specific information about the time span at all up to 24 months. More research is
      needed to identify the degradation behaviour more precisely and clarify the
      potential risks connected to biodegradable implants. Their use should be
      reconsidered critically.

PMID- 20135613
TI  - [Comparison of trunk muscle strength of soccer players with and without low back
      pain].
AB  - AIM OF THE STUDY: Low back pain in soccer players is one of the frequently
      appearing disorders caused by overuse. Myogenic dysbalances are under discussion
      as possible reason for this problem. In the present study the muscular strength
      profile of the trunk musculature of soccer players with and without low back pain
      was evaluated. The results of the asymptomatic players were compared to those of
      players with low back pain; furthermore, the collected data were compared to
      those of an asymptomatic reference group. The question posed was whether soccer
      players show a specific strength profile caused by the special, sports-specific
      requirements and whether this strength profile differs between players with and
      without low back pain. METHOD: In the present study the isometric maximal
      strength of 18 soccer players with and 18 soccer players without low back pain
      was measured in all 3 planes. The reference group was provided by the Proxomed
      company, which had previously analysed 1045 healthy untrained individuals of
      various age groups. RESULTS: The soccer players showed a sport-specific profile
      for the musculature, which was determined by a significant reduction of the
      flexion and rotation strength (flex: O 5.21 N/kg vs. O 6.49 N/kg; O 5.78 N/kg vs.
      O 6.66 N/kg respectively; rotation: left 7.09 N/kg, right 8.69 N/kg vs.
      left/right 10.1 N/kg; left 7.22 N/kg, right 8.24 N/kg vs. left/right 10.0 N/kg,
      respectively) as well as by an increased lateral flexion strength to the right
      hand side in comparison to the reference group (lat. flex. right: 9.87 N/kg,
      respectively, 10.67 N/kg vs. 8.3 N/kg). A statistically significant correlation
      between the muscular activity in the trunk stability of soccer players with and
      without low back pain could not be shown. CONCLUSION: Obviously sports-specific
      training with additional specific training of the trunk muscles is not sufficient
      for the development of a balanced strength of trunk musculature. In the present
      study an influence of the performance of the trunk musculature on the incidence
      of low back pain could not be shown.

PMID- 20135614
TI  - [Preoperative planning and reconstruction in primary total hip arthroplasty with
      and without modular necks].
AB  - STUDY AIM: Preoperative planning is regarded as an important requirement for
      successful implantation of a hip replacement. One of the crucial aspects of
      planning is the restoration of the normal anatomy of the hip as this increases
      the chances for good clinical function and reduces wear debris. Various systems
      for restoration of the hip are available including stem systems with different
      stem sizes and offsets and so-called modular stem systems which have the
      additional possibility of adjusting the neck length and angle. The aim of this
      study was to investigate to what extent a good postoperative outcome can be
      achieved using a modular and a non-modular stem system in comparison with
      preoperative planning. Furthermore, the study assessed the difference between
      preoperative planning carried out by a senior surgeon and by an assistant
      surgeon. METHOD: Standard preoperative and postoperative digitalised radiographs
      with an anteroposterior view of the pelvis centred over the pubic symphysis were
      made. Preoperative planning aimed for exact reconstruction of offset and equal
      leg length. Preoperative planning and evaluation of the postoperative outcome
      were performed by digitalised image-analysing software. The symptom-free
      contralateral hip served as reference for anatomic reconstruction. RESULTS: The
      postoperative results confirmed the preoperative planning. The preoperative
      planning was successfully implemented with both systems. Postoperatively, we
      observed a slightly reduced offset (Group 1: 3.6 mm, Group 2: 3.54 mm) and an
      increase in leg length of less than 5 mm in both groups. There was no significant
      difference between the preoperative planning carried out by the senior surgeon
      and the assistant surgeon. CONCLUSION: Implementation of preoperative planning
      with both the modular and the non-modular system was very satisfactory. It was
      irrelevant if the planning was carried out by a senior surgeon or by an assistant
      surgeon in the first year of training.

PMID- 20135615
TI  - [Perspectives of clinical stem cell therapy in the treatment of musculoskeletal
      diseases in Germany].
AB  - AIM: The treatment of large bone defects remains a challenge for the orthopaedic
      surgeon. Regenerative therapies with the use of mesenchymal stem cells (MSC) may
      provide an alternative to autogenous bone transplantation, callus distraction or
      the use of allografts. MATERIAL AND METHODS: On the occasion of an expert
      workshop of the German Society for Orthopaedic and Trauma Surgery, a literature
      search regarding studies with the use of MSC was performed to evaluate its
      potential for future clinical studies. Furthermore, the legislative requirements
      were examined. RESULTS: Various in vitro and animal studies showed the benefit of
      MSC in bone regeneration. However, there are sparse data from clinical studies.
      Due to recent legislative changes there are several regulatory demands to meet if
      clinical studies are performed with MSC. CONCLUSIONS: For further evaluation of
      the role of MSC in the treatment of bone defects there is a need for clinical
      trials. The current paper provides some assistance for the successful application
      for clinical trials with MSC. Planning and performance of these studies may
      require early consultation with the regulatory authorities and cooperation of
      research centres in order to obtain authorisation for the evaluation of MSC.
      Preclinical data have to be obtained according to good laboratory practice with
      equivalent protocols that will be used in the clinical trials. In the latter the
      implementation of the guidelines for good clinical practice are mandatory.

PMID- 20135616
TI  - [Mid-term results after scaphoid excision and four-corner wrist arthrodesis using
      K-wires for advanced carpal collapse].
AB  - AIM: Successful four-corner fusion after scaphoid excision provides pain relief
      und preserves an acceptable movability of the wrist. However, this treatment
      option for advanced carpal collapse is not without complications, such as
      malunion, hardware impingement or incomplete correction of lunate extension. K
      wires, staples, Herbert screws or, recently, locking plates are all possible
      fixation techniques after scaphoid excision. Only a few studies including mid
      term results using K-wires are available. The aim of our study was to evaluate
      clinical and radiological mid-term results after scaphoid excision and four
      corner arthrodesis using K-wires for stage II and III scapholunate and scaphoid
      non-union advanced collapse. METHOD: Twelve wrists of 11 patients (4/SNAC II
      degrees, 3/SNAC III degrees, 0/SLAC II degrees, 5/SLAC III degrees) were treated
      operatively by scaphoid excision and four-corner arthrodesis. Four K-wires were
      used for osteosynthesis. After an average follow-up of 60.25 months,
      reexamination included subjective, objective and radiological values. Clinical
      examinations covered wrist motion, grip strength and pinch strength. These
      parameters were compared with preoperatively collected data and values of the
      unaffected side. The DASH score (disabilities of the arm, shoulder and hand),
      Cooney score and the visual analogue scale (VAS 0-10) were analysed. Radiographic
      assessment of consolidation was verified by conventional X-rays. The carpal
      height was compared to the preoperative value by assessing the Youm index.
      RESULTS: All patients were satisfied, pain relief was reported and displayed on
      VAS from 7.4 (5-10) to 1.4 (0-5). The mean flexion-extension arc of 76.3 +/- 28.8
      degrees (59.7% of the opposite wrist), preoperatively 75 +/- 17.3 degrees, was
      documented. The average total arc of ulnar and radial deviation was 37.5 +/- 9.2
      degrees (51% of the opposite wrist). The preoperative value was 33.5 +/- 9.8
      degrees. Further clinical evaluation yielded a mean grip strength of 39.3 kp
      (89.5% of the anaffected side) and pinch strength of 7.6 kp (81.7%). Total DASH
      score and Cooney score averaged 15 and 74.17 points, respectively. Osseus
      consolidation was observed radiologically in all patients already after 6 weeks.
      The Youm index decreased from 0.55 +/- 0.054 to 0.51 +/- 0.057. The radiolunate
      joint space remained unaltered in height. There were no infections. Except for
      wire removal, no additional surgery was necessary. CONCLUSION: Scaphoid excision
      and four-corner arthrodesis for advanced collapse of the wrist enjoy great
      satisfaction by the patients, with a high degree of pain reduction. This method
      shows persistent strength and movability in mid-term-results. Compared to
      alternative fixation techniques, the use of K-wires is a low-risk and low-cost
      treatment option, although removal of the K-wires is commonly necessary.

PMID- 20135617
TI  - [Functional results after osteosynthesis of the distal humerus fracture with an
      anatomically precontoured, angular-stable double plate system].
AB  - AIM: The aim of this study was to evaluate the functional results and
      determine/record the complications after treating distal humerus fractures with
      an anatomically precontoured and angular-stable double plate system (LCP Distal
      Humerus Plates, Synthes GmbH, Umkirch). METHOD: 51 patients (30 female, 21 male)
      with 52 fractures of the distal humerus and a mean age of 51 years (14-94) were
      prospectively recorded over a period of 42 months and treated by open reduction
      and internal fixation using the above-mentioned LCP Distal Humerus Plates System.
      Follow-up was performed in 44 patients with 45 fractures after a mean of 13
      months (6-24). According to the classification system introduced by the
      "Arbeitsgemeinschaft fur Osteosynthesefragen" (AO [Association for the study of
      internal fixation, ASIF]) there were six A fractures (13.3%), five B fractures
      (11.1%) and 34 C fractures (75.5%). The AO/ASIF rate of type C3 fractures was
      53%. Seven fractures were grade I (15.6 %) and three fractures grade II (6.7%)
      open. In addition to clinical examination and measuring range of motion (ROM),
      functional results were evaluated using the Mayo elbow performance score (MEPS)
      and the disabilities of the arm, shoulder and hand score (DASH). RESULTS: Using
      the MEPS, excellent results were achieved in 19 patients (43.2%), good in 23
      (52.3%), fair and poor each in one. Mean MEPS was 87.5 +/- 11.8 points (50-100).
      The mean DASH score reached 14.2 +/- 19.9 (0-65.8). Having a mean extension
      deficit of 10 +/- 14.1 degrees (0-40 degrees) and flexion up to 127.5 +/- 17.2
      degrees (80-145 degrees), the mean ROM was 110 +/- 23.8 degrees (50-145 degrees).
      A primary stable osteosynthesis which allows early physiotherapy was gained in 38
      fractures, in seven cases additional immobilisation was carried out (10 to 28
      days). Postoperative complications were seen in eleven patients (24.4%). Overall
      revision surgery was necessary in nine cases. CONCLUSION: By using the
      anatomically precontoured and angular-stable LCP distal humerus plates system a
      stable osteosynthesis allowing early physiotherapy is achieved in the majority of
      patients. Due to early initiation of physical therapy the functional results
      might be improved. Despite using the LCP system complications at the distal
      humerus fracture side were seen frequently, emphasising the challenging surgical
      procedure and demonstrating the need for further implant and surgical procedure
      improvement.

PMID- 20135618
TI  - [Correction of angular deformity of the knee in growing children by temporary
      hemiepiphyseodesis using the eight-plate].
AB  - AIM: Angular deformities of the lower extremity are considered as prearthrotic
      factors. Osteotomy is regarded as a way of corrective treatment. But this
      intervention is considered as complex and requires a special after-treatment.
      During childhood and with remaining growth, guided growth offers an elegant
      solution for this problem. Resulting in a temporary hemiepiphyseodesis, the eight
      Plate offers an alternative technique besides the Blount staples and the
      definitive epiphyseodesis. We evaluated the effect of this device on the
      correction of angular deformities in children with different diagnoses and at
      different ages. METHOD: Since 04/2006 22 patients with angular deformities of the
      lower extremities due to different diagnoses were treated at our department with
      the eight-Plate (42 eight-Plates). In this study we evaluated the outcome of 13
      patients (26 eight-Plates) until the completed angular correction and removal of
      the eight-Plate. A special treatment after plate removal was not applied.
      RESULTS: All patients improved their mechanical leg axis. The average age at
      implantation was 9.4 years (2.3-13.7 years). The average time until plate removal
      was 10.7 months (6-34 months). No hardware failures, extrusions, growth arrests,
      wound infections or other complications were observed. Two patients did not
      achieve the desired axis correction because of insufficient remaining growth
      potential. An additional surgical intervention was realised. The average
      correction of the study group regarding the mechanical axis deviation (MAD) was
      22 mm (6-43 mm) and 10.6 degrees (5-27 degrees) regarding the angular correction
      of the mechanical lateral distal femoral angle (mLDFW). The mechanical medial
      proximal tibial angle (mMPTW) changed by 8.0 degrees (3-15 degrees). CONCLUSION:
      In our opinion the eight-Plate seems to be a safe and reliable device for guided
      growth of angular deformities around the knee. The technique is easy to learn and
      the complication rate low compared to the staple technique. A special after
      treatment is not needed and there is only minor operative trauma. At present
      there are only few data on long-term follow-up after plate removal until skeletal
      maturity. The definition of the ideal point in time for plate removal is still
      open.

PMID- 20135619
TI  - [Perioperative management in outpatient arthroscopy of the knee joint].
AB  - AIM: Nowadays, complex arthroscopic procedures of the knee joint, such as ACL
      reconstruction, are routinely carried out on an outpatient basis. The reduced
      time spent with the patient places high demands on the surgeon with regard to the
      management of such cases. The aim of this study was to evaluate the current
      standards of perioperative management following outpatient arthroscopic surgery
      of the knee in Germany. METHODS: A questionnaire consisting of 18 questions was
      sent to 215 members of the German Association of Outpatient Arthroscopy (BVASK e.
      V.), dealing with the following topics: antibiotic prophylaxis, DVT prophylaxis,
      use of a tourniquet and suction drain, physical therapy, physiotherapy,
      analgesia, anaesthesia and emergency management. More than 51% of the forms were
      returned and considered suitable for statistical analysis. RESULTS: A total of
      62% of the surgeons reported the use of an antibiotic prophylaxis (i. v. single
      shot) in every arthroscopic case, while 19% administer antibiotics only
      occasionally, especially in ACL reconstruction. Postoperative antibiotic
      treatment was reserved for special situations, such as prior joint infection.
      Prophylaxis of DVT by means of low molecular weight heparin was carried out in
      96% of the cases. 51% prescribed anticoagulant agents for 1 week, 39% for the
      duration of reduced weight bearing. Half of the surgeons used a tourniquet cuff,
      22% exsanguinate the limb prior to cuff inflation. A suction drainage was applied
      by 36% of the surgeons regularly and by 45% occasionally. The drain is left for
      one day by 79% of the surgeons, while 11% reported a shortened use of only
      several hours. With regard to analgesia, 66% of all surgeons apply some kind of
      local anaesthetic into the knee joint post surgery. Systemic preoperative
      analgesics or anti-inflammatory agents are given regularly in 56 % of the cases.
      A total of 92% of the procedures are carried out under general anaesthesia. In
      36% of the cases, some kind of additional regional peripheral anaesthesia is
      used. With regard to postoperative care, cryotherapy is considered standard (97%)
      and 64% of the surgeons recommend physiotherapy. Nearly all surgeons (97%) offer
      the patients the opportunity to reach them personally via mobile phone during the
      first night following arthroscopic surgery. CONCLUSIONS: DVT prophylaxis with
      LMWH, general anaesthesia, postoperative cryotherapy and personal availability by
      phone can be considered part of the standard perioperative management following
      outpatient knee arthroscopy in Germany. However, a wide variety of treatment
      options can be found regarding topics such as analgesia, antibiotic prophylaxis,
      tourniquet, knee drainage and physiotherapy.

PMID- 20135620
TI  - [Extra-articular recurrent bleeding from the medial retinaculum].
AB  - A young woman had subcutaneous bleeding at the retinaculum of the left knee after
      minor trauma. A small vein was attached to the scar and repeatedly ruptured after
      several other small traumas. Conservative therapy had no impact on the genesis of
      the bleeding. Having gone through severe bleeding situations with massive
      swelling of the knee five times in a row, the patient underwent surgical
      exploration.The source of recurrent bleeding, a small vein, could be identified
      and excised. After that no further bleeding episodes took place.

PMID- 20135621
TI  - [Operative treatment of femoral head fractures through an anterior minimally
      invasive incision].
AB  - Fractures of the femoral head rarely occur and are often combined with
      dislocation of the hip joint. A separate classification of the femoral head
      fracture was described in 1957 by Pipkin. The operative treatment depends on the
      type of injury and requires extensive knowledge of the various operative
      approaches. We report on a 40-year-old female patient with Pipkin II fracture and
      operative treatment of the injury through an anterior minimally invasive
      incision. We present a review of the literature, evaluate the type of fractures,
      the kind of approaches and treatment and the long-term results. The dislocation
      of the hip should be treated by prompt closed reduction followed by traction and
      immobilization. Open reduction and internal fixation of Pipkin fractures depends
      on the presence of an obstructive fragment, an inability to obtain and maintain
      reduction of either the dislocation of the fracture or both and comminution of
      the fracture bone. When closed methods have failed operation is indicated. The
      operative treatment may include the excision of small fragments, the internal
      fixation with bioabsorbable screws, Herbert screws and the internal fixation of
      femoral neck fractures and acetabular fractures. In some cases salvage procedures
      like endoprotheses are necessary.

PMID- 20135622
TI  - [Oral prevention of thromboembolism with rivaroxaban and dabigatran: are the
      newly approved drugs innovations in orthopaedic and trauma surgery? ].
AB  - Today the indication for thrombosis prophylaxis is a relevant and daily concern
      in orthopaedic surgery. Recently there are some changes concerning the German
      guidelines, which are approved by 27 German medical societies. For the first time
      the guidelines give distinct recommendations for the different indications, the
      kind of thrombosis prophylaxis and its duration. Some of the recommendations will
      lead to changes of both processes in outpatient and inpatient management. In
      parallel 2 new oral anticoagulants have been approved for the prevention of
      thromboembolic events after elective knee and hip replacement. Dabigatran is an
      oral thrombin inhibitor. Compared to enoxaparin it has a comparable profile of
      side effects and efficacy. Rivaroxaban is an oral Xa inhibitor which shows a
      significantly better efficacy compared to enoxaparin and no difference in side
      effects. The significant reduction of symptomatic thromboembolisms after elective
      knee and hip replacement was shown for rivaroxaban compared to enoxaparin in a
      pooled analysis of phase III data. This review discusses the main topics of the
      new German guideline and impact of the new oral anticoagulants on in- and
      outpatient treatment procedures.

PMID- 20135623
TI  - [Prospective evaluation of the effects of a spinal orthosis on physical function
      and quality of life in women with osteoporosis].
AB  - AIM: The aim of this study was to investigate the short- and intermediate-term
      effects of a flexible spinal orthosis on postural control, neuromuscular
      performance, physical activity, fall-related self-efficacy, quality of life and
      perceived pain in osteoporosis. METHOD: 72 postmenopausal osteoporotic women with
      and without vertebral fractures were randomly assigned to receive either a spinal
      orthosis (Thamert Osteo-Med) for 6 months or to a waiting list control. The
      following outcome measures were assessed at baseline and at 3- and 6-months
      follow-up: postural sway, maximum isometric voluntary force of the back extensors
      and quadriceps femoris, physical activity (IPAQ), fall-related self-efficacy (FES
      I), health-related quality of life (QUALEFFO-41) and perceived pain. RESULTS: For
      the orthosis group, repeated measures ANOVA revealed a significant increase in
      trunk extensors muscle strength at 3- and 6-months follow-up and self-perceived
      pain reduction within the 5th month of evaluation in comparison to the control
      group. The remaining parameters showed non-significant changes while wearing the
      orthosis. CONCLUSIONS: The application of the orthosis introduces neuromuscular
      trunk strength improvement in conjunction with pain reduction in women with
      spinal osteoporosis. Future research should evaluate long-term effects on
      habitual physical activity, fall-related fracture risk and health-related quality
      of life.

PMID- 20135625
TI  - Exposure of mouse colon to dietary bile acid supplement induces sessile adenomas.

PMID- 20135626
TI  - The cannabinoid WIN 55,212-2-mediated protection of dentate gyrus granule cells
      is driven by CB1 receptors and modulated by TRPA1 and Cav 2.2 channels.
AB  - Cannabinoids regulate numerous physiological and pathological events like
      inflammation or neurodegeneration via CB(1) and CB(2) receptors. The mechanisms
      behind cannabinoid effects show a high variability and may also involve transient
      receptor potential channels (TRP) and N-type voltage-gated Ca(2+) channels (Ca(v)
      2.2). In the present study we investigated the neuroprotective effects of the
      synthetic cannabinoid WIN 55,212-2 (WIN) on dentate gyrus (DG) granule cells and
      elucidated the involvement of TRP and Ca(v) 2.2 that are shown to participate in
      inflammatory processes. Organotypic hippocampal slice cultures were
      excitotoxically lesioned using NMDA and subsequently incubated with different WIN
      concentrations (0.001-10 MUM). WIN showed neuroprotective properties in an
      inverse concentration-dependent manner, most effectively at 0.01 MUM. The CB(1)
      receptor antagonist AM251 blocked neuroprotection mediated by WIN whereas the
      CB(2) receptor antagonist AM630 showed no effects. Application of the TRPA1
      blocker HC-030031 enhanced the neuroprotective efficacy of high (10 MUM) WIN
      concentrations and the number of degenerating neurons became equal to that seen
      after application of the most effective WIN dose (0.01 MUM). In contrast, the
      application of TRPA1 agonist icilin or allyl isothiocyanate (AITC) led to a
      stronger neurodegeneration. The use of TRPV1 blocker 6-iodo-nordihydrocapsaicin
      did not affect WIN-mediated neuroprotection. The selective Ca(v) 2.2 blocker
      omega-conotoxin (GVIA) completely blocked neuroprotection shown by 10 MUM WIN.
      GVIA and HC-030031 exerted no effects at WIN concentrations lower than 10 MUM.
      Our data show that WIN protects dentate gyrus granule cells in a concentration
      dependent manner by acting upon CB(1) receptors. At high (10 MUM) concentrations
      WIN additionally activates TRPA1 and Ca(v) 2.2 within the hippocampal formation
      that both interfere with CB(1) receptor-mediated neuroprotection. This leads to
      the conclusion that physiological and pharmacological effects of cannabinoids
      strongly depend on their concentration and the neuroprotective efficacy of
      cannabinoids may be determined by interaction of activated CB(1) receptor, TRPA1,
      and Ca(v) 2.2.

PMID- 20135627
TI  - Synthesis and crosslinking of L-DOPA containing polypeptide vesicles.
AB  - The synthesis and self-assembly of DOPA containing diblock copolypeptides into
      spherical vesicles is described. DOPA residues are naturally abundant in mussel
      adhesive proteins and are responsible for extensive covalent crosslinking of
      these materials upon oxidation. We found that vesicles could be formed from
      copolypeptides containing different amounts of DOPA substituted into hydrophobic
      segments, up to 100% DOPA content. The DOPA containing vesicles were covalently
      crosslinked in water using an oxidizing agent, in a process similar to the
      crosslinking of mussel adhesive proteins, which gave vesicles with dramatically
      improved membrane stability against freeze-drying, organic solvent, osmotic
      stress and complex media. These materials showed greatly enhanced membrane
      stability compared to non-crosslinked vesicles and have the advantage that the
      biomimetic crosslinker DOPA can be incorporated directly into the polypeptide
      sequence during synthesis.

PMID- 20135629
TI  - Evaluation of the use of audio-enhanced personal digital assistants to survey
      Latino migrant farmworkers.
AB  - We describe the feasibility of audio-enhanced personal digital assistants (ADPAs)
      for data collection with 60 Latino migrant farmworkers. All participants chose to
      complete APDA surveys rather than using paper-and-pencil. No one left the study
      prematurely: two (3%) data cases were lost due to technical difficulties. Across
      all data .27% missing data were observed: nine missing responses on eight items.
      Participants took 19 minutes on average to complete the 58-question survey. The
      factor most influential for completion was education level. APDA methodology
      enabled both English- and Spanish-speaking Latino migrant farmworkers to become
      active research participants with minimal loss of data.

PMID- 20135628
TI  - Vesicular monoamine transporters: structure-function, pharmacology, and medicinal
      chemistry.
AB  - Vesicular monoamine transporters (VMAT) are responsible for the uptake of
      cytosolic monoamines into synaptic vesicles in monoaminergic neurons. Two closely
      related VMATs with distinct pharmacological properties and tissue distributions
      have been characterized. VMAT1 is preferentially expressed in neuroendocrine
      cells and VMAT2 is primarily expressed in the CNS. The neurotoxicity and
      addictive properties of various psychostimulants have been attributed, at least
      partly, to their interference with VMAT2 functions. The quantitative assessment
      of the VMAT2 density by PET scanning has been clinically useful for early
      diagnosis and monitoring of the progression of Parkinson's and Alzheimer's
      diseases and drug addiction. The classical VMAT2 inhibitor, tetrabenazine, has
      long been used for the treatment of chorea associated with Huntington's disease
      in the United Kingdom, Canada, and Australia, and recently approved in the United
      States. The VMAT2 imaging may also be useful for exploiting the onset of diabetes
      mellitus, as VMAT2 is also expressed in the beta-cells of the pancreas. VMAT1
      gene SLC18A1 is a locus with strong evidence of linkage with schizophrenia and,
      thus, the polymorphic forms of the VMAT1 gene may confer susceptibility to
      schizophrenia. This review summarizes the current understanding of the structure
      function relationships of VMAT2, and the role of VMAT2 on addiction and
      psychostimulant-induced neurotoxicity, and the therapeutic and diagnostic
      applications of specific VMAT2 ligands. The evidence for the linkage of VMAT1
      gene with schizophrenia and bipolar disorder I is also discussed.

PMID- 20135630
TI  - Novel approaches for risk assessment of phytochemicals in food.

PMID- 20135631
TI  - Risk of third and fourth tumors in patients with head and neck cancer.
AB  - BACKGROUND: The objective of our study was to analyze the incidence and location
      of second and subsequent tumors in patients after an index head and neck
      carcinoma. METHODS: A retrospective study was made by reviewing clinical data
      prospectively collected from 3631 patients with head and neck cancer. Incidence,
      location, and histology of the second, third, and fourth tumors was evaluated.
      RESULTS: During the follow-up, 839 second tumors, 147 third tumors, and 35 fourth
      tumors were diagnosed. The annual hazard ratio was 3.8% for second tumors, 5.1%
      for third tumors, and 7.8% for fourth tumors. The risk of second and subsequent
      neoplasms remained constant throughout the follow-up. There were significant
      differences in the risk of appearance between the second and third tumors (p <
      .0001), and between the third and fourth tumors (p = .005). CONCLUSION: Patients
      with a second tumor after an index head and neck carcinoma have an increased risk
      for developing subsequent tumors.

PMID- 20135632
TI  - HIV-1 integrase inhibitors: 2007-2008 update.
AB  - In recent years, HIV-1 integrase (IN) has become an attractive target for
      designing antiretroviral agents. The first IN inhibitor approved for clinical
      use, raltegravir, has validated the pharmacological viability of IN inhibitors
      and signals the advent of a new generation of antiretroviral drugs. The
      development of raltegravir and other successful lead IN inhibitors has also
      influenced the IN inhibitor design strategy. This has led to the identification
      of several potent inhibitors in these last two years. Further, an increased
      understanding of IN structural biology has opened up novel approaches to
      inhibiting IN, such as targeting its multimerization or interaction with cellular
      cofactors. This review covers recent developments in the field of IN inhibitor
      design from 2007 to 2008.  

PMID- 20135633
TI  - Plasma homocysteine levels are associated with ulceration of the foot in patients
      with type 2 diabetes mellitus.
AB  - BACKGROUND: To examine the association of biochemical markers of risk (plasma
      Hcy, microalbuminuria, lipoprotein (a)(Lp(a)) and diabetic dyslipidaemia) with
      the prevalence of diabetic foot ulceration in type 2 diabetic patients. METHODS:
      Case/control study conducted in 198 type 2 diabetic patients. 89 patients have
      foot ulcers and 109 have no foot ulcers (control group), in order to establish
      ORs for diabetic foot ulceration. In all subjects plasma Hcy, Lp(a), total
      cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, apolipoprotein B, HbA(1c) and microalbuminuria were
      measured using standard procedures. RESULTS: Plasma Hcy, microalbuminuria,
      HbA(1c) and apolipoprotein B levels were significantly higher in patients with
      foot ulceration compared with the control group. Plasma lipids, Lp(a), vitamin
      B12 and folic acid values were similar in both groups. In the logistic regression
      model, plasma Hcy (OR 1.09; 95% CI 1.04-1.69), microalbuminuria (OR 1,01; 95% CI
      1.01-1.17) and HbA(1c) levels (OR 1.33; 95% CI 1.04-1.69) were independent risk
      factors for the presence of diabetic foot ulceration. CONCLUSIONS: In our study,
      for each micromol increase in plasma Hcy levels there was a 10% increase in the
      risk of diabetic foot ulceration. In addition, plasma homocysteine, HbA(1c) and
      microalbuminuria accounted for 50% prevalence risk of diabetic foot ulceration.
      Further prospective studies should be conducted to confirm the association of
      plasma Hcy levels with the risk of foot ulceration.

PMID- 20135634
TI  - Conserved water mediated recognition and the dynamics of active site Cys 331 and
      Tyr 411 in hydrated structure of human IMPDH-II.
AB  - Inosine monophosphate dehydrogenase (IMPDH) of human is involved in GMP
      biosynthesis pathway, increased level of IMPDH-II (an isoform of enzyme) activity
      have found in leukemic and sarcoma cells. Modeling and extensive molecular
      dynamics simulation (15 ns) studies of IMPDH-II (1B3O PDB structure) have
      indicated the intricate involvement of four conserved water molecules (W 1, W 2,
      W 3, and W 4) in the conformational transition or the mobilities of "flap"
      (residues 400-450) and "loop" (residues 325-342) regions in enzyme. The
      stabilization of active site residues Asn 303, Gly 324, Ser 329, Cys 331, Asp
      364, and Tyr 411 through variable H-bonding coordination from the conserved water
      molecular center seems interesting in the uninhibited hydrated form of human
      IMPDH-II structures. This conformational transition or the flexibility of mobile
      regions, water molecular recognition to active site residues Cys 331 and Tyr 411,
      and the presence of a hydrophilic cavity approximately 540 A(3) (enclaved by the
      loop and flap region) near the C-terminal surface of this enzyme may explore a
      rational hope toward the water mimic inhibitor or anticancer agent design for
      human.

PMID- 20135635
TI  - Design and fabrication of a robotic mechanism for remote steering and positioning
      of interventional devices.
AB  - BACKGROUND: Recently, robotic systems have been introduced as a method for
      assisting endovascular interventional procedures. A few commercial and research
      solutions are available. In a survey it was found that none of the current
      systems satisfied all basic design requirements set forth for a good robot
      assisted therapy platform. METHODS: A human motion analysis study was performed
      to identify design specifications for safe motion and force limits for
      endovascular surgery. Based on design requirements from surveyed systems and
      motion analysis, a new, teleoperated, haptically enabled system called System for
      Endovascular Teleoperated Access (SETA) was constructed. SETA is capable of
      simultaneously manipulating any guidewire and catheter in the range of 0.014-0.13
      inches. RESULTS: SETA's slave was evaluated for precision positioning, using in
      vitro vascular phantoms. It was also evaluated by a cohort of neurovascular
      surgeons and fellows (n = 8), using the VIST vascular simulator. A qualitative
      survey of the participants and a quantitative analysis of metrics procedure time
      and contrast used found that SETA was equivalent to manual intervention on this
      platform. CONCLUSIONS: SETA provided good performance in the in vitro studies,
      and will soon be evaluated in a series of in vivo animal model studies.

PMID- 20135636
TI  - Protease inhibitors: a panacea?
AB  - With the increasing evidence of protease involvement in several diseases, novel
      strategies for drug development involve the use of protease inhibitors (PIs). The
      local balance between protease inhibitors and proteases is an important
      determinant of the occurrence and progression of a particular disease. Hence,
      enzymes and their cognate inhibitors are finding their applications as diagnostic
      and prognostic markers. PIs are widely implicated for their use in host defense
      against infection, tissue repair and matrix production, blood coagulation,
      cancer, and they are, therefore, the current focus as therapeutic alternatives
      for major diseases such as AIDS and Alzheimer's diseases. This review is a brief
      summary of the varied role of protein protease inhibitors in controlling the
      activity of aberrant enzymes in several diseases afflicting mankind today.

PMID- 20135637
TI  - Influence of p53 expression on sensitivity of cancer cells to bleomycin.
AB  - In this study, we determined whether p53 expression affected the sensitivity of
      non-small cell lung cancer (NSCLC) and colon cancer cells to bleomycin (BLM). Two
      human NSCLC cell lines (A549 expressing wild-type p53 and p53-null H1299) and two
      colon cancer cell lines (HCT116 p53+/+ and its p53 deficient subline HCT116 p53-/
      ) were subjected to treatment with BLM. Cells were treated with various
      concentrations of BLM, and cellular viability was assessed by formazan assay. To
      investigate the role of p53 in BLM sensitivity, we transduced cells with
      adenovirus with wild-type p53, dominant-negative p53, and GFP control, and
      analyzed the effect on cellular viability. Cells expressing wild-type p53 were
      more sensitive to BLM than p53-null cells in both NSCLC and colon cancer cells.
      Sensitivity to BLM of the cells with wild-type p53 was reduced by overexpression
      of dominant-negative p53, while BLM sensitivity of p53-null cells was increased
      by wild-type p53 in both NSCLC cells and colon cancer cells. In conclusion, our
      data show that p53 sensitizes all four cancer cells lines tested to BLM toxicity
      and overexpression of p53 confers sensitivity to the cytotoxic activity of the
      anticancer agent in p53-null cells.

PMID- 20135638
TI  - Screening of herbal extracts against multi-drug resistant Acinetobacter
      baumannii.
AB  - Antibiotic resistance is increasing resulting in a decreasing number of fully
      active antimicrobial agents available to treat infections with multi-drug
      resistant (MDR) bacteria. Herbal medicines may offer alternative treatment
      options. A direct inoculation method simulating the standard disc diffusion assay
      was developed to determine in vitro antimicrobial activity of sixty herbal
      extracts against MDR-Acinetobacter baumannii (A. baumannii). Eighteen herbal
      extracts inhibited MDR-A. baumannii on agar plates, although the magnitude and
      quality of bacterial inhibition differed considerably among the antibacterial
      herbal extracts. Next, minimal inhibitory concentration (MIC) of these
      antibacterial herbal extracts was calculated using a broth microdilution assay.
      For most herbal extracts, the larger the zone of inhibition on agar plates, the
      lower the MIC. In general, hetero-resistance on agar plates correlated with
      higher MIC. The skip well phenomenon was seen with two herbal extracts. In
      conclusion, 30% of the screened herbal extracts demonstrated in vitro
      antibacterial activity against MDR-A. baumannii using similar rigorous testing
      methods as those commonly employed for assessing antimicrobial activity of
      synthetic antibacterial agents. Characterization of a specific compound
      conferring this antibacterial activity of the herbal extracts may help to
      identify novel antimicrobial agents active against highly resistant bacteria.

PMID- 20135639
TI  - Metabolism of the major Echinacea alkylamide N-isobutyldodeca-2E,4E,8Z,10Z
      tetraenamide by human recombinant cytochrome P450 enzymes and human liver
      microsomes.
AB  - Echinacea preparations are used for the treatment and prevention of upper
      respiratory tract infections. The phytochemicals believed responsible for the
      immunomodulatory properties are the alkylamides found in ethanolic extracts, with
      one of the most abundant being the N-isobutyldodeca-2E,4E,8Z,10Z-tetraenamide
      (1). In this study, we evaluated the human cytochrome P450 enzymes involved in
      the metabolism of this alkylamide using recombinant P450s, human liver microsomes
      and pure synthetic compound. Epoxidation, N-dealkylation and hydroxylation
      products were detected, with different relative amounts produced by recombinant
      P450s and microsomes. The major forms showing activity toward the metabolism of 1
      were CYP1A1, CYP1A2 (both producing the same epoxide and N-dealkylation product),
      CYP2A13 (producing two epoxides), and CYP2D6 (producing two epoxides and an
      hydroxylated metabolite). Several other forms showed less activity. In
      incubations with human liver microsomes and selective inhibitors, CYP2E1 was
      found to be principally responsible for producing the dominant, hydroxylation
      product, whereas CYP2C9 was the principal source of the epoxides and CYP1A2 was
      responsible for the dealkylation product. In summary, in this study the relative
      impacts of the main human xenobiotic-metabolizing cytochrome P450s on the
      metabolism of a major Echinacea alkylamide have been established and the
      metabolites formed have been identified.

PMID- 20135640
TI  - Quantitative profiling of mRNA expression of glutathione S-transferase
      superfamily genes in various tissues of bighead carp (Aristichthys nobilis).
AB  - The expression of glutathione S-transferase (GST) is a crucial factor in
      determining the sensitivity of cells and organs in response to a variety of
      toxicants. In this study, we cloned the core nucleotide of alpha, kappa, mu,
      mGST, pi, rho, and theta-like GST genes from bighead carp (Aristichthys nobilis).
      Their derived amino acid sequences were clustered with other vertebrate GSTs in a
      phylogenetic tree, and the bighead carp GST sequences have the highest similarity
      with those from common carp and zebrafish. We quantified the constitutive mRNA
      transcription of GST isoforms in eight different tissues (liver, kidney, spleen,
      intestine, muscle, heart, brain, and gill). The information obtained from the
      present study could be distilled into a few generalized principles: multiple GST
      isoenzymes were ubiquitously expressed in all tissues; majority of GSTs had high
      constitutive expression in intestine, liver, and kidney. These findings are in
      agreement with the roles of these tissues in xenobiotic metabolism. At the same
      time, some unique findings were detected in the current experiment: (1) higher
      expression of most GSTs was observed in spleen; (2) the expression of GST pi was
      highest in almost all the studied tissues except muscle; the other two isoforms,
      GST alpha and rho, were also highly expressed in liver, kidney, intestine,
      spleen, heart, and brain of bighead carp. All these results strongly imply an
      important role of these GST isoforms in detoxification of ingested xenobiotics.

PMID- 20135641
TI  - Involvement of osteopontin upregulation on mesangial cells growth and collagen
      synthesis induced by intermittent high glucose.
AB  - Glucose fluctuations are strong predictor of diabetic vascular complications. We
      explored the effects of constant and intermittent high glucose on the
      proliferation and collagen synthesis of cultured rat mesangial cells.
      Furthermore, the possible involvement of osteopontin (OPN) was assessed. In rat
      mesangial cells cultured in 5, 25, or 5 mmol/L alternating with 25 mmol/L glucose
      in the absence or presence of neutralizing antibodies to OPN, beta3 integrin
      receptor and beta5 integrin receptor, the cell proliferation, collagen synthesis,
      and the expression of OPN and type IV collagen were assessed. In cultured
      mesangial cells, treatment with constant or intermittent high glucose
      significantly increased [(3)H]thymidine incorporation in a time-dependent manner.
      A modest increase was observed at 12 h, and further deteriorated afterwards, and
      reached the maximum incorporation at 48 h. Treatment with constant high glucose
      for 48 h resulted in significant increases in [(3)H]thymidine incorporation, cell
      number, [(3)H]proline incorporation, mRNA, and protein levels of type IV collagen
      and OPN compared with mesangial cells treated with the normal glucose, which were
      markedly enhanced in cells exposed to intermittent high glucose medium. In
      addition, neutralizing antibodies to either OPN or its receptor beta3 integrin
      but not neutralizing antibodies to beta5 integrin can effectively prevented
      proliferation and collagen synthesis of mesangial cells induced by constant or
      intermittent high glucose. Intermittent high glucose exacerbates mesangial cells
      growth and collagen synthesis by upregulation of OPN expression, indicating that
      glycemic variability have important pathological effects on the development of
      diabetic nephropathy, which is mediated by the stimulation of OPN expression and
      synthesis.

PMID- 20135642
TI  - Integrin-linked kinase is involved in TNF-alpha-induced inducible nitric-oxide
      synthase expression in myoblasts.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine produced by
      activated macrophages. Nitric oxide (NO) is a highly reactive nitrogen radical
      implicated in inflammatory responses. We investigated the signaling pathway
      involved in inducible nitric oxide synthase (iNOS) expression and NO production
      stimulated by TNF-alpha in cultured myoblasts. TNF-alpha stimulation caused iNOS
      expression and NO production in myoblasts (G7 cells). TNF-alpha-mediated iNOS
      expression was attenuated by integrin-linked kinase (ILK) inhibitor (KP392) and
      siRNA. Pretreatment with Akt inhibitor, mammalian target of rapamycin (mTOR)
      inhibitor (rapamycin), NF-kappaB inhibitor (PDTC), and IkappaB protease inhibitor
      (TPCK) also inhibited the potentiating action of TNF-alpha. Stimulation of cells
      with TNF-alpha increased ILK kinase activity. TNF-alpha also increased the Akt
      and mTOR phosphorylation. TNF-alpha mediated an increase of NF-kappaB-specific
      DNA-protein complex formation, p65 translocation into nucleus, NF-kappaB
      luciferase activity was inhibited by KP392, Akt inhibitor, and rapamycin. Our
      results suggest that TNF-alpha increased iNOS expression and NO production in
      myoblasts via the ILK/Akt/mTOR and NF-kappaB signaling pathway.

PMID- 20135643
TI  - Glycosaminoglycans modulate RANKL-induced osteoclastogenesis.
AB  - Skeletal integrity is tightly regulated by the activity of osteoblasts and
      osteoclasts that are both under the control of extracellular glycosaminoglycans
      (GAGs) through their interactions with endogenous growth factors and
      differentiation-promoting ligands. Receptor activator of NF-kappa-B ligand
      (RANKL), which is a tumor necrosis factor (TNF)-related protein that is critical
      for osteoclast formation, is produced by osteoblasts and further modulated by
      certain types of GAGs. Using unfractionated osteoblast-derived GAGs that reflect
      the complex tissue microenvironment within which osteoclasts reside, we
      demonstrate that these GAGs block the osteoclastogenic activity of RANKL.
      Furthermore, RANKL significantly reduces extracellular signal-regulated protein
      kinase (ERK) activity, a putative suppressor of osteoclastogenesis, but
      osteoblast-derived GAGs eliminate the inhibitory effects of RANKL on ERK
      activity. Notably, while imposing an anti-osteoclastic effect, these GAGs also
      enhanced the proliferation of osteoblasts. Thus, the osteoblast microenvironment
      is a potent source of GAGs that promote bone anabolic activities. The anti
      osteoclastogenic and osteoblast-related mitogenic activities of these GAGs
      together may provide a key starting point for the development of selective sugar
      based therapeutic compounds for the treatment of osteopenic disorders.

PMID- 20135644
TI  - Statin-induced autophagy by inhibition of geranylgeranyl biosynthesis in prostate
      cancer PC3 cells.
AB  - BACKGROUND: Autophagy is a cellular process of degradation of macromolecules and
      organelles and activated under nutritional stress. Statins are a class of
      inhibitors of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a key
      enzyme in synthesis of cholesterol. Epidemiological studies have shown that
      statin use decreases the incidence of advanced prostate cancer. We explored the
      idea that treatment of atorvastatin, a commonly prescribed statin for treatment
      of hypercholesterolemia, induces autophagy in prostate cancer cells. METHODS: The
      atorvastatin-induced autophagic process in prostate cancer PC3 cells was
      determined by detection of cellular level of LC3-II, an autophagosomal marker,
      via immunoblotting and immunofluorescent staining. RESULTS: Atorvastatin
      treatment of PC3 cells for 40 hrs increased expression of LC3-II by more than 10
      fold in a dose-dependent manner. Treatment of the cells with pepstatin A and E64
      d, the autophagic protease inhibitors, dramatically increased atorvastatin
      dependent LC3-II expression level, suggesting that atorvastatin induces
      autophagic flux. In addition, atorvastatin treatment caused rapid death of PC3
      cells. Atorvastatin-induced autophagy and rapid cell death were reversed by
      addition of geranylgeraniol, not farnesol, into culture medium, indicating that
      atorvastatin-mediated inhibition of geranylgeranyl biosynthesis causes autophagy
      and cell death. Furthermore, atorvastatin did not induce autophagy or cell death
      in normal prostate RWPE1 cells, and induced only a minor autophagic response in
      AR-positive prostate cancer LNCaP cells. CONCLUSIONS: Our studies demonstrate
      that statins induce autophagy and autophagy-associated cell death in PC3 cells,
      likely through inhibition of geranylgeranylation, and suggest that autophagic
      response to statins may partially underlie the protective effects of statins on
      prostate cancer progression. Importantly, these findings highlight additional
      mechanisms by which statins might be used for prostate cancer therapy.

PMID- 20135645
TI  - Effect of aspirin, other NSAIDs, and statins on PSA and PSA velocity.
AB  - BACKGROUND: Aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), and
      statins have been associated with lower risk of prostate cancer and its
      progression, though results have been inconsistent. METHODS: Data from 140 men
      with prostate cancer enrolled in a Phase 2 clinical trial of selenium to prevent
      prostate cancer progression were analyzed to determine association between
      aspirin, other NSAIDs, or statin use with baseline serum prostate-specific
      antigen (PSA) levels and PSA velocity (rate of PSA change over time) using
      repeated measures over an average follow-up time of 3.2 years. Multiple linear
      regression and mixed effects models were used to model the association of
      medication use with PSA at baseline and with PSA velocity, respectively. RESULTS:
      Baseline PSA levels were significantly lower in aspirin users compared to non
      users (5.17 ng/ml vs. 7.58 ng/ml, P = 0.001). This association was statistically
      significant in never smokers (aspirin users vs. non-users: 4.19 ng/ml vs. 8.24
      ng/ml, P = 0.004) but not in ever smokers (aspirin users vs. non-users: 5.52
      ng/ml vs. 7.3 ng/ml, P = 0.101). Statin and other NSAID use was not associated
      with baseline PSA. Aspirin, statin, or other NSAID use at baseline demonstrated a
      non-significant negative association with PSA velocity. CONCLUSION: These
      findings support an effect of aspirin use on PSA, particularly among never
      smokers. However, they do not suggest a protective effect on the disease and
      support previous findings that aspirin use may mask accurate measurement of PSA
      warranting consideration of washout procedures prior to testing.

PMID- 20135647
TI  - Synthesis, structure, and physico-optical properties of manganate(II)-based ionic
      liquids.
AB  - Several ionic liquids (ILs) based on complex manganate(II) anions with chloro,
      bromo, and bis(trifluoromethanesulfonyl)amido (Tf(2)N) ligands have been
      synthesized. As counterions, n-alkyl-methylimidazolium (C(n)mim) cations of
      different chain length (alkyl=ethyl (C(2)), propyl (C(3)), butyl (C(4)), hexyl
      (C(6))) were chosen. Except for the 1-hexyl-3-methylimidazolium ILs, all of the
      prepared compounds could be obtained in a crystalline state at room temperature.
      However, each of the compounds displayed a strong tendency to form a supercooled
      liquid. Generally, solidification via a glass transition took place below -40
      degrees C. Consequently, all of these compounds can be regarded as ionic liquids.
      Depending on the local coordination environment of Mn(2+), green (tetrahedrally
      coordinated Mn(2+)) or red (octahedrally coordinated Mn(2+)) luminescence
      emission from the (4)T(G) level is observed. The local coordination of the
      luminescent Mn(2+) centre has been unequivocally established by UV/Vis as well as
      Raman and IR vibrational spectroscopies. Emission decay times measured at room
      temperature in the solid state (crystalline or powder) were generally a few ms,
      although, depending on the ligand, values of up to 25 ms were obtained. For the
      bromo compounds, the luminescence decay times proved to be almost independent of
      the physical state and the temperature. However, for the chloro- and
      bis(trifluoromethanesulfonyl)amido ILs, the emission decay times were found to be
      dependent on the temperature even in the solid state, indicating that the
      measured values are strongly influenced by nuclear motion and the vibration of
      the atoms. In the liquid state, the luminescence of tetrahedrally coordinated
      Mn(2+) could only be observed when the tetrachloromanganate ILs were diluted with
      the respective halide ILs. However, for [C(3)mim][Mn(Tf(2)N)(3)], in which Mn(2+)
      is in an octahedral coordination environment, a weak red emission from the pure
      compound was found even in the liquid state at elevated temperatures.

PMID- 20135646
TI  - Transforming growth factor beta1 mediates apoptotic activity of angiotensin II
      type I receptor blocker on prostate epithelium in vitro.
AB  - BACKGROUND: The significant association of benign prostatic hyperplasia (BPH) and
      hypertension indicates a common pathophysiological factor for both diseases.
      Hyperactivity of the renin-angiotensin system (RAS) has been reported in BPH.
      Angiotensin II type I (AT1) receptor is the principal mediator of the RAS, and
      the antagonist, AT1 receptor blocker (ARB), can induce apoptosis in prostate
      epithelium cells and increase transforming growth factor beta1 (TGF-beta1)
      expression. We aimed to investigate the mechanism of inhibition of AT1 receptor
      in prostate epithelium cells and the role of TGF-beta1. METHODS: Human prostate
      epithelium cell lines were treated with different concentrations of ARB
      (losartan) (0, 0.1, 1, 10, 100, and 1,000 microM) for 24-72 hr. Cell
      proliferation was analyzed by cell proliferation assay. The location of AT1
      receptor was shown by immunocytohistochemistry and immunocytofluorescence study.
      Analysis of apoptosis was by use of terminal transferase TdT-mediated dUTP-biotin
      end labeling (TUNEL) and caspase 3/7 activity assay. Mitochondrial outer-membrane
      permeabilization was measured by JC-1 staining. The level of TGF-beta1 was
      determined by enzyme-linked immunosorbent assay. RESULTS: Immunohistochemistry
      and immunofluorescence analysis showed AT1 receptor expressed in epithelium
      cells. Compared to control cultures, cultures treated with losartan for 24-72 hr
      showed a dose-dependent significant decrease in cell number, with apoptosis
      increased by 65.2%. Decreased cell number was reversed on treatment with anti-TGF
      beta1 antibody. TUNEL staining showed increased apoptosis in prostate epithelium
      cells exposed to losartan. Caspase 3/7 activation was increased and mitochondrial
      membrane potential was downregulated. Expression of TGF-beta1 in cells treated
      with losartan was higher than that in untreated cells. CONCLUSIONS: The apoptotic
      effect of blockade of AT1 receptor on human prostatic epithelium cells may be
      mediated through an autocrine the production of TGF-beta1. Furthermore, this
      finding may have implications for medication options. Inc.

PMID- 20135648
TI  - Hypergolic N,N-dimethylhydrazinium ionic liquids.
AB  - N,N-Dimethylhydrazinium dicyanamide and nitrocyanamide ionic liquids (ILs) were
      prepared by quaterization of N,N-dimethylhydrazine with alkyl halides followed by
      metathesis reactions with silver dicyanamide or silver nitrocyanamide. The key
      physicochemical properties, such as melting point and decomposition temperatures,
      density, viscosity, heat of formation, detonation pressure and velocity, and
      specific impulse were measured/calculated. The impact of anions and alkyl
      substituted cations on these properties is demonstrated. Droplet tests with white
      fuming nitric acid (WFNA) as an oxidizer were utilized to show that the 14 new
      N,N-dimethylhydrazinium salts are hypergolic with ignition delay (ID) times
      ranging from 22 to 1642 ms, thereby suggesting that some may have potential as
      bipropellants.

PMID- 20135649
TI  - Copper(II) complexes of a hexadentate mixed-donor N3S3 macrobicyclic cage: facile
      rearrangements and interconversions.
AB  - The potentially hexadentate mixed-donor cage ligand 1-methyl-8-amino-3,13,16
      trithia-6,10,19-triazabicyclo[6.6.6]eicosane (AMME-N(3)S(3)sar; sar=sarcophagine)
      displays variable coordination modes in a complex with copper(II). In the absence
      of coordinating anions, the ligand adopts a conventional hexadentate N(3)S(3)
      binding mode in the complex [Cu(AMME-N(3)S(3)sar)](ClO(4))(2) that is typical of
      cage ligands. This structure was determined by X-ray crystallography and solution
      spectroscopy (EPR and NIR UV/Vis). However, in the presence of bromide ions in
      DMSO, clean conversion to a five-coordinate bromido complex [Cu(AMME
      N(3)S(3)sar)Br](+) is observed that features a novel tetradentate (N(2)S(2))
      coordinated form of the cage ligand. This copper(II) complex has also been
      characterized by X-ray crystallography and solution spectroscopy. The mechanism
      of the reversible interconversion between the six- and five-coordinated
      copper(II) complexes has been studied and the reaction has been resolved into two
      steps; the rate of the first is linearly dependent on bromide ion concentration
      and the second is bromide independent. Electrochemistry of both [Cu(AMME
      N(3)S(3)sar)](2+) and [Cu(AMME-N(3)S(3)sar)Br](+) in DMSO shows that upon
      reduction to the monovalent state, they share a common five-coordinated form in
      which the ligand is bound to copper in a tetradentate form exclusively,
      regardless of whether a six- or five-coordinated copper(II) complex is the
      precursor.

PMID- 20135650
TI  - Redox-induced binding of [(tacn)Re(II)Br(CO)2]+ to guanine, oligonucleotides, and
      peptides.

PMID- 20135651
TI  - Chemical-template synthesis of micro/nanoscale magnesium silicate hollow spheres
      for waste-water treatment.
AB  - Micro/nanoscale magnesium silicate hollow spheres were synthesized by using
      silica colloidal spheres as a chemical template in one pot. The hollow spherical
      structure, consisting of well-separated nanoscale units, was microscale as a
      whole and could be easily handled in solution. The as-synthesized magnesium
      silicate hollow spheres with large specific surface area showed availability for
      the removal of organic and heavy-metal ions efficiently from waste water.
      Importantly, the micro/nanoscale magnesium silicate hollow spheres that had
      adsorbed organic pollutants could be regenerated by calcination and used
      repeatedly in pollutant removal. Magnesium silicate hollow spheres synthesized by
      a scaled-up chemical template method may have potential applications in removing
      cationic dyes and heavy-metal ions from waste water.

PMID- 20135653
TI  - Photolysis of aqueous [(NH3)5Os(mu-N2)Os(NH3)5]5+: cleavage of dinitrogen by an
      intramolecular photoredox reaction.

PMID- 20135652
TI  - Small molecule macroarray construction via palladium-mediated carbon-carbon bond
      forming reactions: highly efficient synthesis and screening of stilbene arrays.

PMID- 20135654
TI  - Crystal structure of HIV-1 reverse transcriptase bound to a non-nucleoside
      inhibitor with a novel mechanism of action.

PMID- 20135655
TI  - Allylic substitution versus Suzuki cross-coupling: capitalizing on
      chemoselectivity with bifunctional substrates.

PMID- 20135656
TI  - Supramolecular assemblies formed on an epitaxial graphene superstructure.

PMID- 20135657
TI  - Dynamers at the solid-liquid interface: controlling the reversible
      assembly/reassembly process between two highly ordered supramolecular guanine
      motifs.

PMID- 20135658
TI  - Indium(I)-catalyzed asymmetric allylation, crotylation, and alpha
      chloroallylation of hydrazones with rare constitutional and high configurational
      selectivities.

PMID- 20135659
TI  - Parallel and antiparallel triple helices of naphthyridine oligoamides.

PMID- 20135660
TI  - Facile interconversion of [Cp2(Cl)Hf(SnH3)] and [Cp2(Cl)Hf(mu-H)SnH2]: DFT
      investigations of hafnocene stannyl complexes as masked stannylenes.

PMID- 20135661
TI  - Asymmetric direct vinylogous aldol reaction of furanone derivatives catalyzed by
      an axially chiral guanidine base.

PMID- 20135662
TI  - Catalytic enantioselective Dieckmann-type annulation: synthesis of pyrrolidines
      with quaternary stereogenic centers.

PMID- 20135663
TI  - Chemical RNA modifications for studies of RNA structure and dynamics.

PMID- 20135664
TI  - Stereoselective ring expansion of vinyl oxiranes: mechanistic insights and
      natural product total synthesis.

PMID- 20135665
TI  - Synthetic chain terminators off-load intermediates from a type I polyketide
      synthase.
AB  - Modular biocatalysis is responsible for the generation of countless bioactive
      products and its mining remains a major focus for drug discovery purposes. One of
      the enduring hurdles is the isolation of biosynthetic intermediates in a readily
      analysed form. We prepared a series of nonhydrolysable pantetheine and N-acetyl
      cysteamine mimics of the natural (methyl)malonyl extender units recruited for
      polyketide formation. Using these analogues as competitive substrates, we were
      able to trap and off-load diketide and triketide species directly from an in
      vitro reconstituted type I polyketide synthase, the 6-deoxyerythronolide B
      synthase 3 (DEBS3). The putative intermediates, which were extracted in organic
      solvent and characterised by LC-HR-ESI-MS, are the first of their kind and prove
      that small-molecule chain terminators can be used as convenient probes of the
      biosynthetic process.

PMID- 20135666
TI  - Electronic and vibrational coherence dynamics in a cyanine dye studied using a
      few-cycle pulsed laser.
AB  - We report the relaxation times of electronic and vibrational coherence in the
      cyanine dye 1,1',3,3,3',3'-hexamethyl-4,4',5,5'-dibenzo-2,2'-indotricarbocyanine,
      measured using a 7.1 fs pulsed laser. The vibrational phase relaxation times are
      found to be between 380 and 680 fs in the ground and lowest excited singlet
      states. The vibrational dephasing times of the 294, 446, and 736 cm(-1) modes are
      relatively long among the six modes associated with excited-state wave packets.
      The slower relaxations are explained in terms of a coupled triplet of vibrational
      modes, which preserves coherence by forming a tightly bound group to satisfy the
      condition of circa conservation of vibrational energy. Using data from the
      negative-time range (i.e., when the probe pulse precedes the pump pulse), the
      electronic phase relaxation time is found to be 31+/-1 fs. The dynamic
      vibrational mode in the excited state (1171 cm(-1)), detected in the positive
      time range, is also studied from the negative-time traces under the same
      experimental conditions.

PMID- 20135667
TI  - Development of a benzopyran-containing androgen receptor antagonist to treat
      antiandrogen-resistant prostate cancer.

PMID- 20135668
TI  - Ion and pH sensing with colloidal nanoparticles: influence of surface charge on
      sensing and colloidal properties.
AB  - Ion sensors based on colloidal nanoparticles (NPs), either as actively ion
      sensing NPs or as nanoscale carrier systems for organic ion-sensing fluorescent
      chelators typically require a charged surface in order to be colloidally stable.
      We demonstrate that this surface charge significantly impacts the ion binding and
      affects the read-out. Sensor read-out should be thus not determined by the bulk
      ion concentration, but by the local ion concentration in the nano-environment of
      the NP surface. We present a conclusive model corroborated by experimental data
      that reproduces the strong distance-dependence of the effect. The experimental
      data are based on the capability of tuning the distance of a pH-sensitive
      fluorophore to the surface of NPs in the nanometer (nm) range. This in turn
      allows for modification of the effective acid dissociation constant value (its
      logarithmic form, pK(a)) of analyte-sensitive fluorophores by tuning their
      distance to the underlying colloidal NPs.

PMID- 20135669
TI  - Anticancer activity of vitamin E-derived compounds in murine C6 glioma cells.

PMID- 20135670
TI  - Synthesis of thia-analogous indirubin N-Glycosides and their influence on
      melanoma cell growth and apoptosis.

PMID- 20135671
TI  - Rational design, synthesis, biophysical and antiproliferative evaluation of
      fluorenone derivatives with DNA G-quadruplex binding properties.
AB  - Molecular modeling studies carried out with experimental DNA models with the
      sequence d[AG(3)(T(2)AG(3))(3)] suggest that the introduction of a net positive
      charge onto the side chain of a series of fluorenone carboxamides can improve G
      quadruplex binding. The terminal morpholino moiety was replaced with a novel N
      methylmorpholinium cation starting from two 4-carboxamide compounds. A different
      substitution on the fluorenone ring was also investigated and submitted to the
      same quaternarization process. All compounds were analyzed for their DNA binding
      properties by competition dialysis methods. In vitro antiproliferative tests were
      carried out against two different tumor cell lines. Docking experiments were
      conducted by including all four known human repeat unit G-quadruplex DNA
      sequences (27 experimentally determined conformations) against the most active
      fluorenone derivatives. The results of theoretical, biophysical, and in vitro
      experiments indicate two novel derivatives as lead compounds for the development
      of a new generation of G-quadruplex ligands with greater potency and selectivity.

PMID- 20135672
TI  - Organic polyaromatic hydrocarbons as sensitizing model dyes for semiconductor
      nanoparticles.
AB  - The study of interfacial charge-transfer processes (sensitization) of a dye bound
      to large-bandgap nanostructured metal oxide semiconductors, including TiO(2),
      ZnO, and SnO(2), is continuing to attract interest in various areas of renewable
      energy, especially for the development of dye-sensitized solar cells (DSSCs). The
      scope of this Review is to describe how selected model sensitizers prepared from
      organic polyaromatic hydrocarbons have been used over the past 15 years to
      elucidate, through a variety of techniques, fundamental aspects of heterogeneous
      charge transfer at the surface of a semiconductor. This Review does not focus on
      the most recent or efficient dyes, but rather on how model dyes prepared from
      aromatic hydrocarbons have been used, over time, in key fundamental studies of
      heterogeneous charge transfer. In particular, we describe model chromophores
      prepared from anthracene, pyrene, perylene, and azulene. As the level of
      complexity of the model dye-bridge-anchor group compounds has increased, the
      understanding of some aspects of very complex charge transfer events has
      improved. The knowledge acquired from the study of the described model dyes is of
      importance not only for DSSC development but also to other fields of science for
      which electronic processes at the molecule/semiconductor interface are relevant.

PMID- 20135673
TI  - The effect of high-energy extracorporeal shock waves on hyaline cartilage of
      adult rats in vivo.
AB  - The aim of this study was to determine if extracorporeal shock wave therapy
      (ESWT) in vivo affects the structural integrity of articular cartilage. A single
      bout of ESWT (1500 shock waves of 0.5 mJ/mm(2)) was applied to femoral heads of
      18 adult Sprague-Dawley rats. Two sham-treated animals served as controls.
      Cartilage of each femoral head was harvested at 1, 4, or 10 weeks after ESWT (n =
      6 per treatment group) and scored on safranin-O-stained sections. Expression of
      tenascin-C and chitinase 3-like protein 1 (Chi3L1) was analyzed by
      immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was
      used to examine collagen (II)alpha(1) (COL2A1) expression and chondrocyte
      morphology was investigated by transmission electron microscopy no changes in
      Mankin scores were observed after ESWT. Positive immunostaining for tenascin-C
      and Chi3L1 was found up to 10 weeks after ESWT in experimental but not in control
      cartilage. COL2A1 mRNA was increased in samples 1 and 4 weeks after ESWT.
      Alterations found on the ultrastructural level showed expansion of the rough
      surfaced endoplasmatic reticulum, detachment of the cell membrane and necrotic
      chondrocytes. Extracorporeal shock waves caused alterations of hyaline cartilage
      on a molecular and ultrastructural level that were distinctly different from
      control. Similar changes were described before in the very early phase of
      osteoarthritis (OA). High-energy ESWT might therefore cause degenerative changes
      in hyaline cartilage as they are found in initial OA.

PMID- 20135674
TI  - Endothelial progenitor cells promote fracture healing in a segmental bone defect
      model.
AB  - The objective of this study was to evaluate the effects of local endothelial
      progenitor cell (EPC) therapy on bone regeneration in a rat model. A segmental
      bone defect (5 mm) was created in the femur and fixed with a mini-plate. There
      were two groups: EPC-treated (N = 28) and control (N = 28). Seven animals were
      sacrificed from each group at 1, 2, 3, and 10 weeks postoperatively. Healing of
      the defect was evaluated with radiographic, histological, and quantitative micro
      computed tomography (micro-CT) scans. Radiographically, mean scores of the EPC
      and control groups were, respectively, 1.16-0.61 (p < 0.05) at 1 week, 2.53-1.54
      (p < 0.05) at 2 weeks, and 4.58-2.35 at 3 weeks (p < 0.05). At 10 weeks, all the
      animals in the EPC-treated group had complete union (7/7), but in the control
      group none achieved union (0/7). Histological evaluation revealed that specimens
      from EPC-treated animals had abundant new bone and vessel formation compared to
      that in controls. Micro-CT assessment of the samples from the animals sacrificed
      at 10 weeks (N = 14) showed significantly improved parameters of bone volume
      (36.58-10.57, p = 0.000), bone volume density (0.26-0.17, p = 0.000), model index
      -2.22-2.79, p = 0.000), trabecular number (1.28-0.91, p = 0.063), trabecular
      thickness (0.21-0.15, p = 0.001), trabecular spacing (0.63-1.07, p = 0.022), bone
      surface (353.75-152.08, p = 0.000), and bone surface to bone volume ratio (9.54
      14.24, p = 0.004) for the EPC group compared to control, respectively. In
      conclusion, local EPC therapy significantly enhanced bone regeneration in a
      segmental defect model in rat femur diaphysis.

PMID- 20135675
TI  - A pilot study of prolonged exposure therapy for posttraumatic stress disorder
      delivered via telehealth technology.
AB  - The authors present a pilot study of 12 veterans diagnosed with combat-related
      PTSD and treated with prolonged exposure therapy (PE) via telehealth technology.
      A reference sample of 35 combat veterans treated with in-person PE in the same
      clinic is also included for a comparison. Feasibility and clinical outcomes of
      interest include technical performance and practicality of the telehealth
      equipment, patient safety, treatment completion rates, number of sessions
      required for termination, and clinical outcomes. Results indicated large
      statistically significant decreases in self-reported pathology for veterans
      treated with PE via telehealth technology. Preliminary results support the
      feasibility and safety of the modality. Suggestions for the implementation of PE
      via telehealth technology are discussed.

PMID- 20135676
TI  - Incapacitated, forcible, and drug/alcohol-facilitated rape in relation to binge
      drinking, marijuana use, and illicit drug use: a national survey.
AB  - This study examined the relation between rape and substance use problems as a
      function of three legally recognized forms of rape: forcible, incapacitated, and
      drug/alcohol facilitated rape. Data were collected via structured telephone
      interview within a national household sample of U.S. women aged 18-34 years (n =
      1,998). Lifetime experience of incapacitated rape was associated with increased
      odds of past-year binge drinking, marijuana use, and illicit drug use. Lifetime
      history of forcible rape and drug/alcohol facilitated rape were associated with
      increased odds of marijuana and illicit drug use. Findings highlight the
      importance of including incapacitated and drug/alcohol facilitated rape in trauma
      history assessments, particularly among substance abusing populations, and have
      implications for secondary prevention and treatment of women with victimization
      histories.

PMID- 20135677
TI  - Understanding the impact of the wars in Iraq and Afghanistan.

PMID- 20135678
TI  - Measurement invariance of posttraumatic stress disorder symptoms among U.S.
      military personnel.
AB  - Studies have not examined the factor structure or measurement invariance of
      posttraumatic stress disorder (PTSD) symptomatology using population-based data.
      Confirmatory factor analysis of the PTSD Checklist-Civilian Version (PCL-C) was
      conducted in a representative sample of U.S. active duty military personnel (N =
      15,593). Consistent with prior research, a 4-factor model consisting of
      reexperiencing, avoidance, emotional numbing, and arousal factors was superior to
      four alternative models. Measurement invariance was found for factor loadings,
      but not observed item intercepts when comparing personnel with and without a
      recent deployment (<or=12 months). Findings indicate differences in the level of
      observed responses across deployment subgroups that exceed what would be expected
      for individuals with similar PCL latent factors scores. Implications of results
      are discussed.

PMID- 20135679
TI  - Transient neutropenia increases macrophage accumulation and cell proliferation
      but does not improve repair following intratendinous rupture of Achilles tendon.
AB  - Neutrophils are the first leukocytes to invade tendons after an acute injury.
      They could modulate both the inflammatory response and early repair processes
      through the release of reactive species, cytokines, growth factors, and
      proteinases. However, the exact role of these cells in damaged tendons remains
      unclear. We investigated their role by inducing a transient neutropenia in
      C57BL/6 male mice using an anti-Ly6C/Ly6G antibody. Placebo mice received only
      serum. The right Achilles tendon was sectioned and sutured using the 8-strand
      technique, which allowed immediate weight bearing. A significant increase in
      macrophage accumulation and cell proliferation was observed in tendons from
      neutropenic animals compared to the placebo group at days 3 and/or 7 postinjury.
      However, there was a reduction in cell proliferation in a group of mice depleted
      in macrophages, indicating that macrophages play a role in cell replication in
      injured tendons. Lastly, the tendons of neutropenic and placebo mice had similar
      collagen content and mechanical properties at days 7, 14, and/or 28 postinjury.
      Our findings demonstrate that neutropenia modulates macrophage accumulation and
      cell proliferation, but overall, a reduction in neutrophil number has no
      significant effect on tendon repair.

PMID- 20135680
TI  - Adult separation anxiety disorder among war-affected Bosnian refugees:
      comorbidity with PTSD and associations with dimensions of trauma.
AB  - Although separation anxiety disorder appears to be common among children exposed
      to disasters, there are no data focusing on the impact of trauma on adult
      separation anxiety disorder. The present exploratory study examined the
      relationship of adult separation anxiety disorder with other psychological
      reactions (posttraumatic stress disorder [PTSD], complicated grief, depression)
      and dimensions of trauma among 126 war-affected Bosnian refugees resettled in
      Australia. Adult separation anxiety disorder was associated with PTSD, but not
      with complicated grief or depression. Although adult separation anxiety disorder
      was weakly linked with traumatic losses, this association was nonspecific.
      Further research is needed to clarify the pathogenic pathways leading to the
      comorbid PTSD-adult separation anxiety disorder pattern and its clinical
      implications.

PMID- 20135681
TI  - Predeployment gender differences in stressors and mental health among U.S.
      National Guard troops poised for Operation Iraqi Freedom deployment.
AB  - Increased exposure of women soldiers to combat in current conflicts heightens
      interest in the question of whether risk and resilience factors differ for female
      and male military personnel prior to deployment. The authors examined this
      question in a panel of 522 National Guard soldiers (462 men and 60 women) poised
      for deployment to Iraq. Soldiers completed a battery of self-report measures,
      including the PTSD Checklist, Beck Depression Inventory-II, and scales from the
      Deployment Risk and Resilience Inventory. Modest differences were observed
      between women and men on predeployment risk factors and some risk-related
      correlations with PTSD and depression measures; however, gender did not moderate
      the associations between hypothesized risk/resilience factors and baseline mental
      health. Implications for interventions and future research are discussed.

PMID- 20135682
TI  - Differentiation and characterization of metabolically functioning hepatocytes
      from human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) may provide a cell source for functional
      hepatocytes for clinical applications and drug development. Initially, the hESC
      population was enriched to be more than 85% definitive endoderm (DE) as assessed
      by the expression of CXCR4, SOX17, and FOXA2. We then successfully converted DE
      into hepatic progenitors with 93% of the cells being positive for alpha-feto
      protein within 9 days. The percentage of albumin positive cells gradually
      increased to 90% at days 20-22 after differentiation. Moreover, our hESC-derived
      hepatocytes (hEH) developed a complete biotransformation system including phase I
      and II metabolizing enyzmes and phase III transporters. Nuclear receptors, which
      are critical in regulating the expression of metabolizing enzymes, were also
      expressed by our hEH. Using ultraperformance liquid chromatography-tandem mass
      spectrometry technology, we identified seven metabolic pathways of the drug
      bufuralol including four newly-reported ones in our hEH, which are the same as
      those in freshly isolated human primary hepatocytes (hPH). In addition, the
      results of the metabolism of four drugs indicate that our hEH have the capacity
      to metabolize these drugs at levels that are comparable to hPH. In conclusion, we
      have generated a relatively homogenous population of hepatocytes from hESCs,
      which appear to have complete metabolic function that is comparable to primary
      liver cells. These results represent a significant step towards the efficient
      differentiation of mature hepatocytes for cell-based therapeutics as well as for
      pharmacology and toxicology studies.

PMID- 20135683
TI  - Hypoxia influences the vascular expansion and differentiation of embryonic stem
      cell cultures through the temporal expression of vascular endothelial growth
      factor receptors in an ARNT-dependent manner.
AB  - Adaptive responses to low oxygen (O(2)) tension (hypoxia) are mediated by the
      heterodimeric transcription factor hypoxia inducible factor (HIF). When
      stabilized by hypoxia, bHLH-PAS alpha- and beta- (HIF-1beta or ARNT) HIF complex
      regulate the expression of multiple genes, including vascular endothelial growth
      factor (VEGF). To investigate the mechanism(s) through which hypoxia contributes
      to blood vessel development, we used embryonic stem cell (ESC) differentiation
      cultures that develop into embryoid bodies (EBs) mimicking early embryonic
      development. Significantly, low O(2) levels promote vascular development and
      maturation in wild-type (WT) ESC cultures measured by an increase in the numbers
      of CD31(+) endothelial cells (ECs) and sprouting angiogenic EBs, but refractory
      in Arnt(-/-) and Vegf(-/-) ESC cultures. Thus, we propose that hypoxia promotes
      the production of ECs and contributes to the development and maturation of
      vessels. Our findings further demonstrate that hypoxia alters the temporal
      expression of VEGF receptors Flk-1 (VEGFR-2) and the membrane and soluble forms
      of the antagonistic receptor Flt-1 (VEGFR-1). Moreover, these receptors are
      distinctly expressed in differentiating Arnt(-/-) and Vegf(-/-) EBs. These
      results support existing models in which VEGF signaling is tightly regulated
      during specific biologic events, but also provide important novel evidence that,
      in response to physiologic hypoxia, HIF mediates a distinct stoichiometric
      pattern of VEGF receptors throughout EB differentiation analogous to the
      formation of vascular networks during embryogenesis.

PMID- 20135684
TI  - Isolation of a highly myogenic CD34-negative subset of human skeletal muscle
      cells free of adipogenic potential.
AB  - The differentiation of multipotent cells into undesirable lineages is a
      significant risk factor when performing cell therapy. In muscular diseases,
      myofiber loss can be associated with progressive fat accumulation that is one of
      the primary factors leading to decline of muscular strength. Therefore, to avoid
      any contribution of injected multipotent cells to fat deposition, we have
      searched for a highly myogenic but nonadipogenic muscle-derived cell population.
      We show that the myogenic marker CD56, which is the gold standard for myoblast
      based therapy, was unable to separate muscle cells into myogenic and adipogenic
      fractions. Conversely, using the stem cell marker CD34, we were able to sort two
      distinct populations, CD34(+) and CD34(-), which have been thoroughly
      characterized in vitro and in vivo using an immunodeficient Rag2(-/-)gamma(c) (-/
      ) mouse model of muscle regeneration with or without adipose deposition. Our
      results demonstrate that both populations have equivalent capacities for in vitro
      amplification. The CD34(+) cells and CD34(-) cells exhibit equivalent myogenic
      potential, but only the CD34(-) population fails to differentiate into adipocytes
      in vitro and in vivo after transplantation into regenerative fat muscle. These
      data indicate that the muscle-derived cells constitute a heterogeneous population
      of cells with various differentiation potentials. The simple CD34 sorting allows
      isolation of myogenic cells with no adipogenic potential and therefore could be
      of high interest for cell therapy when fat is accumulated in diseased muscle.

PMID- 20135685
TI  - Radiation resistance of cancer stem cells: the 4 R's of radiobiology revisited.
AB  - There is compelling evidence that many solid cancers are organized hierarchically
      and contain a small population of cancer stem cells (CSCs). It seems reasonable
      to suggest that a cancer cure can be achieved only if this population is
      eliminated. Unfortunately, there is growing evidence that CSCs are inherently
      resistant to radiation, and perhaps other cancer therapies. In general, success
      or failure of standard clinical radiation treatment is determined by the 4 R's of
      radiobiology: repair of DNA damage, redistribution of cells in the cell cycle,
      repopulation, and reoxygenation of hypoxic tumor areas. We relate recent findings
      on CSCs to these four phenomena and discuss possible consequences.

PMID- 20135686
TI  - Glycan-based high-affinity ligands for toxins and pathogen receptors.
AB  - Glycans decorate over 95% of the mammalian cell surface in the form of
      glycolipids and glycoproteins. Several toxins and pathogens bind to these glycans
      to enter the cells. Understanding the fundamentals of the complex interplay
      between microbial pathogens and their glycan receptors at the molecular level
      could lead to the development of novel therapeutics and diagnostics. Using Shiga
      toxin and influenza virus as examples, we describe the complex biological
      interface between host glycans and these infectious agents, and recent strategies
      to develop glycan-based high-affinity ligands. These molecules are expected to
      ultimately be incorporated into diagnostics and therapeutics, and can be used as
      probes to study important biological processes. Additionally, by focusing on the
      specific glycans that microbial pathogens target, we can begin to decipher the
      "glycocode" and how these glycans participate in normal and aberrant cellular
      communication.

PMID- 20135687
TI  - An enriched structural kinase database to enable kinome-wide structure-based
      analyses and drug discovery.
AB  - The development of a kinase structural database, the kinase knowledge base (KKB),
      is described. It covers all human kinase domain structures that have been
      deposited in the Protein Data Bank. All structures are renumbered using a common
      scheme, which enables efficient cross-comparisons and multiple queries of
      interest to the kinase field. The common numbering scheme is also used to
      automatically annotate conserved residues and motifs, and conformationally
      classify the structures based on the DFG-loop and Helix C. Analyses of residue
      conservation in the ATP binding site using the full human-kinome-sequence
      alignment lead to the identification of a conserved hydrogen bond between the
      hinge region backbone and a glycine in the specificity surface. Furthermore, 90%
      of kinases are found to have at least one stabilizing interaction for the hinge
      region, which has not been described before.

PMID- 20135688
TI  - Overview of developmental and reproductive toxicity research in China: history,
      funding mechanisms, and frontiers of the research.
AB  - Reproductive and developmental toxicology (DART) is the discipline that deals
      with adverse effects on male and female resulting from exposures to harmful
      chemical and physical agents. DART research in China boasted a long history, but
      presently has fallen behind the western world in education and research. The
      funding mechanisms for DART research in China were similar to that for other
      toxicological disciplines, and the funding has come from research grants and
      fellowships provided by national, ministerial, and provincial institutions.
      Finally, the frontiers of DART research in China could be summarized as follows:
      (1) use of model animals such as the zebrafish and roundworm, and use of cutting
      edge techniques such as stem cell culture, as well as transgenic, metabonomic,
      and virtual screening to study the mechanisms of developmental toxicity for some
      important toxicants in China; (2) use of model animals and other lower-level
      sentinel organisms to evaluate and monitor the developmental toxicogical risk of
      environmental chemicals or pollutants; (3) epidemiological studies of some
      important reproductive hazards; (4) in-depth studying of the reproductive and
      developmental toxicity of some important environmental chemicals; and (5)
      evaluation and study of the reproductive and developmental toxicity of
      traditional Chinese medicines.

PMID- 20135689
TI  - Radial shock waves effectively introduced NF-kappa B decoy into rat achilles
      tendon cells in vitro.
AB  - The purpose of this study was to test if radial shock waves could enhance the
      introduction of nuclear factor-kappa B (NF-kappaB) decoy oligodeoxynucleotides,
      which is reported to markedly inhibit NF-kappaB activation and suppress pro
      inflammatory cytokine gene expression, using rat Achilles tendon cells. In the
      presence of NF-kappaB decoy labeled with or without fluorescein isothiocyanate
      (FITC) in culture media, radial shock waves were applied to the tendon cells in
      variable conditions and cultivated for 24 h. The transfection rate was assessed
      by counting FITC-positive cells, and IL-1-induced NF-kappaB activation in the
      cells was assessed. Radial shock waves significantly enhanced introduction of NF
      kappaB decoy-FITC into the tendon cells. IL-1-induced NF-kappaB activation was
      significantly inhibited by pretreatment of the cells with NF-kappaB decoy
      combined with radial shock wave exposure. The present study demonstrated the
      effectiveness of radial shock waves on introduction of NF-kappaB decoy into
      tendon cells. Radial shock wave treatment combined with local NF-kappaB decoy
      administration could be a novel therapeutic strategy for chronic tendinopathy.

PMID- 20135690
TI  - In vitro investigation of friction under edge-loading conditions for ceramic-on
      ceramic total hip prosthesis.
AB  - Edge-loading generates higher wear rates in ceramic-on-ceramic total hip
      prosthesis (THP). To investigate the friction coefficient (FC) in these
      conditions, three alumina ceramic (Biolox Forte) 32 mm-diameter components were
      tested using a hip friction simulator. The cup was positioned with a 75 degrees
      abduction angle to achieve edge-loading conditions. The motion was first applied
      along the edge and then across the edge of the cup. First, tests were conducted
      under lubricated conditions with 25% bovine serum. Next, to simulate an extremely
      high contact pressure, the tests were run with the addition of a third body
      alumina ceramic chip inserted between the edge of the cup and the head.
      Engineering blue was used to analyze the contact area. Reference values were
      determined using a 0 degrees cup abduction angle. Edge loading was achieved. The
      FC increased by three- to sixfold when the motion was applied along the edge, and
      by 70% when the motion was applied across the edge. However, the FC value was
      still low (about 0.1), which is similar to metal-on-metal THP. With the third
      body alumina ceramic particle inserted, the FC was 26 times higher than in the
      ideal conditions and intermittent squeaking occurred. High cup abduction angles
      may generate edge-loading and an increase in the friction coefficient for ceramic
      THP.

PMID- 20135691
TI  - Near infrared imaging with nanoparticles.
AB  - Near infrared imaging has presented itself as a powerful diagnostic technique
      with potential to serve as a minimally invasive, nonionizing method for
      sensitive, deep tissue diagnostic imaging. This potential is further realized
      with the use of nanoparticle (NP)-based near infrared (NIR) contrast agents that
      are not prone to the rapid photobleaching and instability of their organic
      counterparts. This review discusses applications that have successfully
      demonstrated the utility of nanoparticles for NIR imaging, including NIR-emitting
      semiconductor quantum dots (QDs), resonant gold nanoshells, and dye-encapsulating
      nanoparticles. NIR QDs demonstrate superior optical performance with exceptional
      fluorescence brightness stability. However, the heavy metal composition and high
      propensity for toxicity hinder future application in clinical environments. NIR
      resonant gold nanoshells also exhibit brilliant signal intensities and likewise
      have none of the photo- or chemical-instabilities characteristic of organic
      contrast agents. However, concerns regarding ineffectual clearance and long-term
      accumulation in nontarget organs are a major issue for this technology. Finally,
      NIR dye-encapsulating nanoparticles synthesized from calcium phosphate (CP) also
      demonstrate improved optical performances by shielding the component dye from
      undesirable environmental influences, thereby enhancing quantum yields, emission
      brightness, and fluorescent lifetime. Calcium phosphate nanoparticle (CPNP)
      contrast agents are neither toxic, nor have issues with long-term sequestering,
      as they are readily dissolved in low pH environments and ultimately absorbed into
      the system. Though perhaps not as optically superior as QDs or nanoshells, these
      are a completely nontoxic, bioresorbable option for NP-based NIR imaging that
      still effectively improves the optical performance of conventional organic
      agents.

PMID- 20135692
TI  - Gastrointestinal parasites of Howler monkeys (Alouatta palliata) inhabiting the
      fragmented landscape of the Santa Marta mountain range, Veracruz, Mexico.
AB  - In recent years populations of howler monkeys (Alouatta palliata) in southeastern
      Mexico have decreased substantially due to the transformation and loss of natural
      habitats. This is especially evident in the Santa Marta mountain range, Veracruz,
      Mexico where several studies have evaluated the impact of fragmentation on howler
      monkey populations in order to propose management programs for their
      conservation. The conditions generated by fragmentation likely change the rates
      of parasitic infection and could decrease howler survival. In this study,
      gastrointestinal parasite species richness, prevalence, and egg density of
      infection were determined in howler groups inhabiting five forest fragments at
      the Santa Marta mountain range. Two hundred and seventy-eight fresh fecal samples
      were collected between October 2002 and April 2003. Three parasite species were
      found during the dry and the wet season in all forest fragments sampled: one
      unidentified species of Eimeriidae; Trypanoxyuris minutus (Oxyuridae); and
      Controrchis biliophilus (Dicrocoeliidae). Both the prevalence of T. minutus and
      infection density for all parasites differed between seasons and fragments (the
      largest fragment consistently differed from other fragments). Host density,
      distance to the nearest town, fragment size, fragment shape, and total basal area
      of food trees explained parasite prevalence, but each species had a different
      pattern. Although parasite richness was lower, prevalence and density were higher
      than values reported for howlers in conserved forests. These results suggest that
      the establishment of biological corridors and animal translocation programs must
      take into account the parasite ecology of each fragment to avoid higher infection
      rates and preclude potential consequent mortality.

PMID- 20135693
TI  - Release liner removal method for transdermal drug delivery systems (TDDS).
AB  - A release liner removal test is a valuable test for assessing the quality of a
      transdermal drug delivery system (i.e., TDDS, patch). This test measures the
      force required to remove the release liner from a patch. The objective of the
      present study was to establish sample preparation and instrument parameters for
      measuring release liner removal adhesion for TDDS. Ten TDDS were evaluated (six
      drugs for a total of 29 lots). Patches which had a rate-controlling membrane were
      run as-is, since they could not be cut to a precise width without sacrificing
      their structural integrity. Patches that were square or rectangular in shape were
      run as-is, and the width of these patches was determined using a digital caliper.
      Patches which were not square or rectangular in shape and did not have a rate
      controlling membrane were cut to a precise width using a specimen cutter. Double
      sided tape was used to adhere the liner side of the transdermal system to a clean
      stainless steel test panel. A release liner peel adhesion method for TDDS is
      proposed using a dwell time of approximately 3 min, a peel angle of 90 degrees ,
      and a peel speed of 300 mm/min.

PMID- 20135694
TI  - A critical assessment of the ICH guideline on photostability testing of new drug
      substances and products (Q1B): Recommendation for revision.
AB  - The ICH guideline on photostability (ICH Topic Q1B) was published in November
      1996 and has been implemented in all three regions (US, EU, and Japan). The
      guideline describes a useful basic protocol for testing of new drug substances
      and associated drug products for manufacturing, storage, and distribution, but it
      does not cover the photostability of drugs under conditions of patient use. The
      pharmaceutical industry now has considerable experience in designing and carrying
      out photostability studies within the context of this guideline, and issues have
      been identified that would benefit from the revision process. The purpose of this
      commentary is to accomplish the following: (i) highlight issues proposed for
      consideration in the ICH revision process, (ii) offer a rationale for why these
      issues may compromise the design of a testing protocol and/or the results of the
      testing program, and (iii) provide recommendations for clarification of the
      guideline.

PMID- 20135695
TI  - Granulocyte colony stimulating factor in neonatal alloimmune neutropenia: a
      possible association with induced thrombocytopenia.
AB  - Neonatal alloimmune neutropenia (NAIN) is a rare cause of congenital neutropenia
      seen in <1% of births. Significant morbidity, usually infections, may result from
      this disease. The pathophysiology of NAIN, mediated by maternal antibodies
      crossing the placenta to destroy fetal cells expressing paternal antigens, is
      similar to that of neonatal alloimmune thrombocytopenia, as well as Rh/ABO
      hemolytic disease of the newborn. The use of high-dose granulocyte colony
      stimulating factor in patients with NAIN may cause a reversible thrombocytopenia
      in some patients.

PMID- 20135696
TI  - Anxiety is contagious-symptoms of anxiety in the terminally ill child affect long
      term psychological well-being in bereaved parents.
AB  - BACKGROUND: We studied the relation between unrelieved symptoms in terminally ill
      children and the psychological well-being in the bereaved parents 4-9 years after
      their loss. PROCEDURE: We contacted parents in Sweden who had lost a child to a
      malignancy 1992-1997. The parents were asked to assess symptoms affecting their
      child's well-being during his or her last month of life, and their own current
      psychological well-being. RESULTS: Altogether 449/561 (80%) eligible parents
      supplied information on 19 specific symptoms that may occur in children with a
      malignancy and how each of these symptoms had affected their child's well-being
      during his or her last month of life (not applicable, none, low, moderate, or
      severe). These results were linked to questions concerning the parents' self
      assessed mental health. Parents of children who were affected by disturbed sleep
      also had increased risk to develop these symptoms; RR 2.0 [1.4-2.9] for
      depression, 1.8 [1.3-2.5] for anxiety, 1.5 [1.2-1.8] for decreased psychological
      well-being, and 1.5 [1.3-1.9] for decreased quality of life. CONCLUSIONS:
      Bereaved parents whose children were affected by anxiety or disturbed sleep due
      to anxiety or pain had an increased risk of long-term psychological morbidity.
      Reducing psychological complications in seriously ill children may also improve
      the psychological well-being in bereaved parents.

PMID- 20135697
TI  - siRNA applications in nanomedicine.
AB  - The ability to specifically silence genes using RNA interference (RNAi) has wide
      therapeutic applications for the treatment of disease or the augmentation of
      tissue formation. RNAi is the sequence-specific gene silencing mediated by a 21
      25 nucleotide double-stranded small interfering RNA (siRNA) molecule. siRNAs are
      incorporated into the RNA-induced silencing complex (RISC), which mediates mRNA
      sequence-specific binding and cleavage. Although RNAi has the potential to be a
      powerful therapeutic drug, its delivery remains a major limitation. The
      generation of nanosized particles is being investigated to enhance the delivery
      of siRNA-based drugs. These nanoparticles are generally designed to overcome one
      or more of the barriers encountered by the siRNA when trafficked to the cytosol.
      In this review, we will discuss recent advances in the design of delivery
      strategies for siRNA, focusing our attention to those strategies that have had in
      vivo success or have introduced novel functionality that allowed enhanced
      intracellular trafficking and/or cellular targeting. First, we will discuss the
      different barriers that must be overcome for efficient siRNA delivery. Second, we
      will discuss the approaches for siRNA delivery by size including direct
      modification of siRNAs (less than 10 nm), self-assembled particles based on
      cationic polymers and cationic lipids (100-300 nm), neutral liposomes (<200 nm),
      and macroscale matrices that contain naked siRNA or siRNA loaded nanoparticles
      (>100 microm). Finally, we will briefly discuss recent in vivo therapeutic
      success.

PMID- 20135698
TI  - PTSD symptom increases in Iraq-deployed soldiers: comparison with nondeployed
      soldiers and associations with baseline symptoms, deployment experiences, and
      postdeployment stress.
AB  - This prospective study examined: (a) the effects of Iraq War deployment versus
      non-deployment on pre- to postdeployment change in PTSD symptoms and (b) among
      deployed soldiers, associations of deployment/postdeployment stress exposures and
      baseline PTSD symptoms with PTSD symptom change. Seven hundred seventy-four U.S.
      Army soldiers completed self-report measures of stress exposure and PTSD symptom
      severity before and after Iraq deployment and were compared with 309 soldiers who
      did not deploy. Deployed soldiers, compared with non-deployed soldiers, reported
      increased PTSD symptom severity from Time 1 to Time 2. After controlling for
      baseline symptoms, deployment-related stressors contributed to longitudinal
      increases in PTSD symptoms. Combat severity was more strongly associated with
      symptom increases among active duty soldiers with higher baseline PTSD symptoms.

PMID- 20135699
TI  - Disparate prevalence estimates of PTSD among service members who served in Iraq
      and Afghanistan: possible explanations.
AB  - The authors reviewed 29 studies that provide prevalence estimates of
      posttraumatic stress disorder (PTSD) among service members previously deployed to
      Operations Enduring and Iraqi Freedom and their non-U.S. military counterparts.
      Studies vary widely, particularly in their representativeness and the way PTSD is
      defined. Among previously deployed personnel not seeking treatment, most
      prevalence estimates range from 5 to 20%. Prevalence estimates are generally
      higher among those seeking treatment: As many as 50% of veterans seeking
      treatment screen positive for PTSD, though much fewer receive a PTSD diagnosis.
      Combat exposure is the only correlate consistently associated with PTSD. When
      evaluating PTSD prevalence estimates among this population, researchers and
      policymakers should carefully consider the method used to define PTSD and the
      population the study sample represents.

PMID- 20135700
TI  - Psychosocial and functional outcomes in long-term survivors of osteosarcoma: a
      comparison of limb-salvage surgery and amputation.
AB  - BACKGROUND: Traditionally, physicians have believed that limb-salvage surgery has
      functional and cosmetic advantages over amputation, yet the literature is
      equivocal. Therefore, we sought to compare the psychosocial and functional
      outcomes in osteosarcoma survivors after limb-salvage surgery and amputation. We
      hypothesized there to be neither psychosocial nor functional outcome differences
      between groups. PROCEDURE: Participants received treatment of extremity
      osteosarcoma, had received their cancer diagnosis at least 2 years prior, and
      were at least 16 years old. A comprehensive set of validated psychosocial and
      functional measures was used to assess outcome. RESULTS: Fifty-seven patients
      participated in this study (33 who underwent limb-salvage surgery and 24 who
      underwent amputation). Participants had gone 12-24 years since diagnosis and were
      16-52 years old at study participation. We used multiple linear regression models
      to examine differences in quality of life, body image, self-esteem, and social
      support between the two groups and found no differences. Lower limb function was
      a significant predictor of quality of life (P < 0.001), whereas surgery type did
      not impact this relationship. Body image was rated significantly worse by those
      who underwent late amputation, amputation after failed limb salvage, than by
      those who did not. CONCLUSIONS: Participants with more functional lower limbs had
      better quality of life than did those with less functional lower limbs regardless
      of whether they underwent amputation or limb-salvage surgery.

PMID- 20135701
TI  - Variability of pulse oximetry measurement over 1 year in children with sickle
      cell disease depends on initial oxygen saturation measurement.
AB  - A prospective cohort of children with sickle cell disease (SCD) was evaluated to
      determine the variability of daytime pulse oximetry among three measurements over
      approximately 1 year. Fifty-eight participants were evaluated. Asymptomatic
      children with initial oxygen saturation < or = 92% had a mean range over 1 year
      of 4.6% (2.1-7.5%). In contrast, asymptomatic children whose oxygen saturation
      was >92% had a mean range of 1.9% (0-5.5%). These results suggest, changes in
      pulse oximetry measurement of approximately 5% may not be clinically significant
      in otherwise, healthy children with SCD with previous pulse oximetry < or = 92%.

PMID- 20135702
TI  - Kawasaki disease preceding haemophagocytic lymphohistiocytosis: challenges for
      developing world practitioners.
AB  - Kawasaki disease (KD) is a recognised precipitant of haemophagocytic
      lymphohistiocytosis (HLH). Although KD has been previously described in the
      developing world, there are no reported cases of KD preceding HLH. We report a
      case of a child with a persistent rash and unremitting fever consistent with the
      diagnosis of KD, who was found to have HLH, after intravenous gamma globulin
      failed to produce a clinical response. The diagnosis was made using the revised
      diagnostic criteria for HLH from the Histiocyte Society (1994). She fulfilled six
      of the eight clinical and laboratory criteria needed to make the diagnosis.

PMID- 20135703
TI  - Post-hematopoietic stem cell transplant immunization practices in the Pediatric
      Blood and Marrow Transplant Consortium.
AB  - BACKGROUND: A survey of National Marrow Donor Program transplant centers in 1995
      demonstrated a wide range of immunization practices in post-hematopoietic stem
      cell transplant (HSCT) recipients, which led to the 2000 Centers for Disease
      Control and Prevention (CDC) recommendations for vaccination after HSCT. We
      surveyed the principal investigators of the Pediatric Blood and Marrow Transplant
      Consortium (PBMTC) to identify immunization practice patterns after HSCT and
      assess compliance with the 2000 CDC guidelines. PROCEDURE: Approval was obtained
      from the Medical University of South Carolina Institutional Review Board. A 33
      question survey using surveymonkey.com was distributed by email to principal
      investigators in the PBMTC. RESULTS: Forty-one (40%) of the 102 pediatric HSCT
      centers participating in the PBMTC responded. Thirty of the responding centers
      completed the entire survey. For individual vaccines, compliance with the CDC
      guidelines ranged from 22% to 93%. Less than 20% of the centers reported
      schedules consistent with the 2000 CDC recommendations for both allogeneic and
      autologous HSCT recipients. CONCLUSION: Despite the 2000 CDC guidelines, wide
      variation in post-HSCT immunization practices still exists. Updated guidelines
      have been needed, particularly to address the use of the pneumococcal conjugate
      vaccine. In conjunction with multiple other groups, the CDC recently released new
      immunization guidelines in October 2009. Additional data are still needed to
      adequately address the utility of incorporating immunologic parameters with the
      timing of vaccination after HSCT.

PMID- 20135704
TI  - Study of nobiletin binding to bovine serum albumin by capillary electrophoresis
      frontal analysis and circular dichroism.
AB  - A very recent epidemiological study provided strong support for nobiletin (NOB)
      as a potential candidate chemopreventive agent against cancer. From the
      pharmacology point of view, drug-protein interactions are determining factors in
      therapeutic, pharmacodynamic and toxicological drug properties. In this work, for
      the first time, detection of NOB at near-physiological conditions was
      accomplished by means of capillary electrophoresis-frontal analysis (CE-FA), and
      then the binding constants of NOB with bovine serum albumin (BSA) at the same
      conditions were determined. Complexation of NOB-BSA led to a decrease of the
      height for free NOB with increasing concentration of BSA. These results revealed
      the presence of a single class of binding site on BSA, and provided the binding
      constant of 10(3)/m, showing the strong affinity of NOB for BSA. Furthermore,
      circular dichroism spectra showed that, when the molar ratio of NOB to BSA was up
      to 2:1, NOB did not affect the overall protein conformation significantly and the
      protein thus retained a native-like structure. These results may provide
      important information for preclinical studies of nobiletin in pharmaceutical
      research.

PMID- 20135706
TI  - Hydrophilic interaction LC of peptides: columns comparison and clustering.
AB  - A wide variety of hydrophilic interaction chromatography (HILIC) stationary phase
      surface chemistries are currently available. Although their selectivity can be
      considerably different, column comparison or clustering using peptides is
      limited. In this study, ten pharmaceutically relevant model peptides are analyzed
      on seven different HILIC columns (bare silica, amide, poly-hydroxyethyl
      aspartamide, diol and zwitterionic) for the evaluation of their performance and
      classification. The responses examined include single and multiple responses:
      plate number, asymmetry factor, LOD, geometric mean resolution, resolution
      product, time corrected resolution product, peak capacity and chromatographic
      response function. Column classification was performed using hierarchical
      clustering and principal component analysis. Moreover, the overall performance
      quality of the HILIC columns was compared using a linear desirability function.
      Hierarchical clustering and principal component analysis showed consistent
      clusters. The zwitterionic phase was clustered apart from the other HILIC columns
      and both poly-aspartamide columns were clustered together. In addition, the two
      bare silica phases represent two different clusters, and thus different
      selectivities. Overall, the responses showed the best performance for one of the
      bare silica columns (Alltima-Alltech), followed by the zwitterionic phase (ZIC)
      HILIC. Thus, these columns, belonging to different clusters, were found to be the
      best performing systems in pharmaceutical peptide analysis for the selected
      peptide set.

PMID- 20135707
TI  - Simultaneous qualitative and quantitative analysis of 28 components in Isodon
      rubescens by HPLC-ESI-MS/MS.
AB  - A novel method, HPLC-MS/MS was developed to qualitatively identify and
      quantitatively determine the 28 components including 19 diterpenoids, 6 phenolic
      acids and 3 flavonoids in Isodon rubescens, an important traditional Chinese
      medicine. The separation was performed on a C(18) column with linear gradient
      elution with 0.1% aqueous formic acid/methanol containing 0.1% formic acid at a
      flow rate of 0.7 mL/min. The identification and quantification of those analytes
      were achieved on a hybrid quadrupole linear ion trap mass spectrometer. Multiple
      reaction monitoring scanning was employed for quantification with switching
      electrospray ion source polarity between positive and negative modes in a single
      run. Full validation of the method was carried out (linearity, precision,
      accuracy, LOD and LOQ). The results indicated that the method was simple, rapid,
      specific and reliable. The proposed method was successfully applied for the
      qualitative and quantitative analysis of 28 chemical compositions in 21 batches
      of natural and cultured I. rubescens samples from different sources which had
      great variation on the contents. The results demonstrated that the method was
      useful for standardization and differentiation of large numbers of similar
      samples.

PMID- 20135708
TI  - 2-D RP/RPLC method to separate components in Fructus schisandrae chinensis.
AB  - An off-line 2-D RP/RPLC method was developed to separate components in extracts
      of Fructus schisandrae chinensis, which is a traditional Chinese medicine. In
      this method, Click beta-CD stationary phase was proposed for constructing 2-D
      RP/RPLC system combined with C18 column. Beta-CD column showed great potential to
      separate compounds in traditional Chinese medicines under RP mode. Collected
      fractions from Click beta-CD column used in first dimension were resolved into
      many additional components, indicating that the 2-D LC system based on Click beta
      CD and C18 phases is orthogonal. The mobile phase was same on both columns. This
      2-D LC method facilitates us not only to separate components that cannot be
      resolved by unidimensional chromatography, but also to achieve much more
      efficient detection of minor sample components.

PMID- 20135709
TI  - A RP-HPLC-DAD-APCI/MSD method for the characterisation of medicinal Ericaceae
      used by the Eeyou Istchee Cree First Nations.
AB  - INTRODUCTION: Ericaceae medicinal plants are traditionally used by the Eeyou
      Istchee Cree and other northern peoples of North America to treat type 2 diabetic
      symptoms. Because of the importance of phenolics as potential cures for
      degenerative diseases including type 2 diabetes, an analytical method was
      developed to detect them in the leaf extracts of 14 Ericaceae plants. OBJECTIVE:
      To develop an optimised method which is applicable to a relatively large number
      of Ericaceae plants using their leaf extracts. For this purpose phenolics with a
      wide range of polarity, including a glucosylated benzoquinone, two phenolic
      acids, three flavanols, a flavanone, a flavone and five flavonols, were included
      in this study. METHODOLOGY: Characterisation of phytochemicals in extracts was
      undertaken by automated matching to the UV spectra to those of an in house
      library of plant secondary metabolites and the authentication of their identity
      was achieved by reversed phase-high-performance chromatography-diode array
      detection-atmospheric pressure chemical ionisation/mass selective detection.
      RESULTS: Twenty-six phenolics were characterised within 26 min of chromatographic
      separation in 80% ethanol extracts of 14 Ericaceae plants. The calibration curves
      were linear within 0.5-880 microg/g dry mass of the plant with regression values
      better than 0.995. The limits of detection ranged from 0.3 for microg/mL for (+)
      catechin to 2.6 microg/mL for chlorogenic acid. This is a first study dealing
      with relatively large number of Ericaceae extracts and is applicable to other
      plants of same family.

PMID- 20135710
TI  - A reliable and efficient method for total rna isolation from various members of
      spurge family (Euphorbiaceae).
AB  - INTRODUCTION: It is prerequisite and crucial to extract RNA with high quality and
      integrity in order to carry out molecular biology studies in any plant species of
      a family. Euphorbiaceae members are known for high levels of their waxes, oils
      with polysaccharides, polyphenolics and secondary metabolites. These conditions
      are recognised to interfere unfavourably with various methodologies of RNA
      isolation. OBJECTIVE: To develop a simple, rapid and reproducible
      cetyltrimethylamonium bromide (CTAB)-based protocol, to reduce the time and cost
      of extraction without reducing quality and yield of RNA extracted from various
      recalcitrant Euphorbiaceae member plant tissues such as from tree leaves (Hevea
      brasilensis), woody shrubs leaves (Ricinus communis, Jatropha curcas, Manihot
      esculenta) and storage root tissue (M. esculenta). METHODOLOGY: Simple
      modifications and fast steps were introduced to the original CTAB protocol. All
      centrifugation steps were carried out at 4 degrees C at 12000 rpm for 10 min, the
      sample weight was decreased and usage of spermidine and LiCl was omitted,
      reducing incubation time prior to RNA precipitation. This rapid CTAB protocol was
      compared with various RNA isolation methods intended for use with plants rich in
      polysaccharides and secondary metabolites. RESULTS: The procedure can be
      completed within 2 h and many samples can be processed at the same time. RNA of
      high quality could be isolated from all the tissues of species that we tried. The
      isolated RNA from different species served as a robust template for RT-PCR
      analysis. CONCLUSION: The study has shown that the improvement of a CTAB-based
      protocol allows the rapid isolation of high-quality RNA from various recalcitrant
      Euphorbiaceae members.

PMID- 20135711
TI  - Simultaneous determination of four iridoid and secoiridoid glycosides and
      comparative analysis of Radix Gentianae Macrophyllae and their related
      substitutes by HPLC.
AB  - INTRODUCTION: Radix Gentianae Macrophyllae, a traditional Chinese medicine, has
      been frequently used to dispel rheumatism and ease pain. There are four species
      of Gentiana (G. macrophylla, G. straminea, G. dahurica and G. crassicaulis)
      recorded as herbal drugs in the Chinese Pharmacopoeia and two other Gentiana
      species (G. officinalis and G. siphonantha) are often used as substitutes.
      Currently, the LC fingerprint comparison among different species and evidence for
      the equivalent application of these herbs are lacking. OBJECTIVE: To develop an
      HPLC method for the simultaneous determination of four iridoid and secoiridoid
      glycosides and a comparative study of six species of Gentiana. METHODOLOGY: HPLC
      analysis was performed on a C(18) column (Phenomenex, 150 x 4.6 mm, 5 microm
      particle size) with gradient elution using 0.4% aqueous phosphoric acid and
      methanol at 242 nm. RESULTS: The proposed method was precise, accurate and
      sensitive enough for simultaneous quantitative evaluation of four iridoid and
      secoiridoid glycosides (loganic acid, swertiamarin, gentiopicroside and
      sweroside) in the six species of Gentiana. Contents of the four marker compounds
      varied from each other even among the samples from the same species and the LC
      chromatograms of the six species of Gentiana showed high similarities.
      CONCLUSION: he close similarity of LC chromatograms and chemical composition of
      the four genuine Gentiana species explain their popular usage as Radix Gentianae
      Macrophyllae in Chinese medicine. By comparing the four genuine Gentiana species,
      it is suggested that the two substitutes could be used as Radix Gentianae
      Macrophyllae to relieve the scarcity of resources.

PMID- 20135712
TI  - Is the DHEAS/cortisol ratio a potential filter for non-operable constipated
      cases?
AB  - Constipation is a significant manifestation of a number of psychological
      disorders. Published papers recommend using self-assessment questionnaires for
      discriminating psychological from non-psychological constipated patients before
      operating on them but reports from major surveys revealed that general
      practitioners failed to diagnose 70% of depressed patients using self-assessment
      questionnaires. Lower circulating concentrations of progesterone, 17
      hydroxyprogesterone, cortisol, testosterone, androstenedione, and
      dehydroepiandrostenedione sulfate (DHEAS) during the follicular phase in
      constipated young women compared with respective controls were found during the
      follicular phase of the menstrual cycles. During the luteal phase of the cycle,
      reductions were identified in estriol, cortisol and testosterone in the
      constipated group. Likewise, circulating concentrations of DHEAS were found to be
      lower in depressed patients than comparable healthy controls. DHEAS/cortisol
      ratios in morning serum and salivary samples were lower than those retrieved
      during other times of the day in depressed patients. The idea of recognizing
      major depression in constipated patients by measuring DHEAS/cortisol ratios in
      saliva and serum may be plausible but this possibility needs to be confirmed in
      well-designed studies.

PMID- 20135713
TI  - Iron: an emerging factor in colorectal carcinogenesis.
AB  - The carcinogenic potential of iron in colorectal cancer (CRC) is not fully
      understood. Iron is able to undergo reduction and oxidation, making it important
      in many physiological processes. This inherent redox property of iron, however,
      also renders it toxic when it is present in excess. Iron-mediated generation of
      reactive oxygen species via the Fenton reaction, if uncontrolled, may lead to
      cell damage as a result of lipid peroxidation and oxidative DNA and protein
      damage. This may promote carcinogenesis through increased genomic instability,
      chromosomal rearrangements as well as mutations of proto-oncogenes and tumour
      suppressor genes. Carcinogenesis is also affected by inflammation which is
      exacerbated by iron. Population studies indicate an association between high
      dietary iron intake and CRC risk. In this editorial, we examine the link between
      iron-induced oxidative stress and inflammation on the pathogenesis of CRC.

PMID- 20135714
TI  - Recent developments in palliative chemotherapy for locally advanced and
      metastatic pancreas cancer.
AB  - In spite of advances made in the management of the other more common cancers of
      the gastrointestinal tract, significant progress in the treatment of pancreatic
      cancer remains elusive. Nearly as many deaths occur from pancreatic cancer as are
      diagnosed each year reflecting the poor prognosis typically associated with this
      disease. Until recently, the only treatment with an impact on survival was
      surgery. In the palliative setting, gemcitabine (Gem) has been a standard
      treatment for advanced pancreatic cancer since it was shown a decade ago to
      result in a superior clinical benefit response and survival compared with bolus 5
      fluorouracil. Since then, clinical trials have explored the pharmacokinetic
      modulation of Gem by fixed dose administration and the combination of Gem with
      other cytotoxic or the biologically "targeted" agents. However, promising trial
      results in small phase II trials have not translated into survival improvements
      in larger phase III randomized trials in the advanced disease setting. Two trials
      have recently reported modest survival improvements with the use of combination
      treatment with Gem and capecitabine (United Kingdom National Cancer Research
      GEMCAP trial) or erlotinib (National Cancer Institute of Canada Clinical Trials
      Group PA.3 trial). This review will focus on the use of systemic therapy for
      advanced and metastatic pancreatic cancer, summarizing the results of several
      recent clinical trials and discuss their implications for clinical practice. We
      will also discuss briefly the second-line chemotherapy options for advanced
      pancreatic cancer.

PMID- 20135715
TI  - Experience of a single center with congenital hepatic fibrosis: a review of the
      literature.
AB  - Congenital hepatic fibrosis (CHF) is an autosomal recessive inherited
      malformation defined pathologically by a variable degree of periportal fibrosis
      and irregularly shaped proliferating bile ducts. It is one of the fibropolycystic
      diseases, which also include Caroli disease, autosomal dominant polycystic kidney
      disease, and autosomal recessive polycystic kidney disease. Clinically it is
      characterized by hepatic fibrosis, portal hypertension, and renal cystic disease.
      CHF is known to occur in association with a range of both inherited and non
      inherited disorders, with multiorgan involvement, as a result of ductal plate
      malformation. Because of the similarities in the clinical picture, it is
      necessary to differentiate CHF from idiopathic portal hypertension and early
      liver cirrhosis, for which a liver biopsy is essential. Radiological tests are
      important for recognizing involvement of other organ systems. With regards to our
      experience at Hacettepe University, a total of 26 patients have been diagnosed
      and followed-up between 1974 and 2009 with a diagnosis of CHF. Presentation with
      Caroli syndrome was the most common diagnosis, with all such patients presenting
      with symptoms of recurrent cholangitis and symptoms related to portal
      hypertension. Although portal fibrosis is known to contribute to the ensuing
      portal hypertension, it is our belief that portal vein cavernous transformation
      also plays an important role in its pathogenesis. In all patients with CHF portal
      vein morphology should be evaluated by all means since portal vein involvement
      results in more severe and complicated portal hypertension. Other associations
      include the Joubert and Bardet-Biedl syndromes.

PMID- 20135716
TI  - How useful is rectal endosonography in the staging of rectal cancer?
AB  - It is essential in treating rectal cancer to have adequate preoperative imaging,
      as accurate staging can influence the management strategy, type of resection, and
      candidacy for neoadjuvant therapy. In the last twenty years, endorectal
      ultrasound (ERUS) has become the primary method for locoregional staging of
      rectal cancer. ERUS is the most accurate modality for assessing local depth of
      invasion of rectal carcinoma into the rectal wall layers (T stage). Lower
      accuracy for T2 tumors is commonly reported, which could lead to sonographic
      overstaging of T3 tumors following preoperative therapy. Unfortunately, ERUS is
      not as good for predicting nodal metastases as it is for tumor depth, which could
      be related to the unclear definition of nodal metastases. The use of multiple
      criteria might improve accuracy. Failure to evaluate nodal status could lead to
      inadequate surgical resection. ERUS can accurately distinguish early cancers from
      advanced ones, with a high detection rate of residual carcinoma in the rectal
      wall. ERUS is also useful for detection of local recurrence at the anastomosis
      site, which might require fine-needle aspiration of the tissue. Overstaging is
      more frequent than understaging, mostly due to inflammatory changes. Limitations
      of ERUS are operator and experience dependency, limited tolerance of patients,
      and limited range of depth of the transducer. The ERUS technique requires a
      learning curve for orientation and identification of images and planes. With
      sufficient time and effort, quality and accuracy of the ERUS procedure could be
      improved.

PMID- 20135717
TI  - Capillaria hepatica in China.
AB  - Capillaria hepatica (C. hepatica) is a parasitic nematode causing hepatic
      capillariasis in numerous mammals. Ecologic studies showed that the first hosts
      of C. hepatica were rodents, among which rats had relatively high infection
      rates, which explains why C. hepatica spreads globally. Anatomical studies showed
      that the liver was the principal site of colonization by these parasites and
      physical damage tended to occur. Although C. hepatica might lead to serious liver
      disorders, relevant clinical reports were rare, because of the non-specific
      nature of clinical symptoms, leading to misdiagnosis. This review mainly focuses
      on the biological characteristics and epidemiology of C. hepatica in China and
      histopathologic changes in the liver, with expectation of gaining a better
      understanding of the disease and seeking more effective treatment.

PMID- 20135718
TI  - Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances
      during experimental colitis in mice.
AB  - AIM: To investigate the therapeutic effect of Schistosoma mansoni (S. mansoni)
      soluble worm proteins on gastrointestinal motility disturbances during
      experimental colitis in mice. METHODS: Colitis was induced by intrarectal
      injection of trinitrobenzene sulphate (TNBS) and 6 h later, mice were treated ip
      with S. mansoni proteins. Experiments were performed 5 d after TNBS injection.
      Inflammation was quantified using validated inflammation parameters. Gastric
      emptying and geometric center were measured to assess in vivo gastrointestinal
      motility. Peristaltic activity of distal colonic segments was studied in vitro
      using a modified Trendelenburg set-up. Cytokine profiles of T-lymphocytes
      isolated from the colon were determined by real time reverse transcriptase
      polymerase chain reaction. RESULTS: Intracolonic injection of TNBS caused severe
      colitis. Treatment with S. mansoni proteins significantly ameliorated colonic
      inflammation after 5 d. TNBS did not affect gastric emptying but significantly
      decreased the geometric center and impaired colonic peristaltic activity 5 d
      after the induction of colitis. Treatment with S. mansoni proteins ameliorated
      these in vivo and in vitro motility disturbances. In addition, TNBS injection
      caused a downregulation of effector T cell cytokines after 5 d, whereas a S.
      mansoni protein effect was no longer observed at this time point. CONCLUSION:
      Treatment with S. mansoni proteins attenuated intestinal inflammation and
      ameliorated motility disturbances during murine experimental colitis.

PMID- 20135719
TI  - Involvement of PI3K and ERK1/2 pathways in hepatocyte growth factor-induced
      cholangiocarcinoma cell invasion.
AB  - AIM: To investigate the role of hepatocyte growth factor (HGF) in
      cholangiocarcinoma (CCA) cell invasiveness and the mechanisms underlying such
      cellular responses. METHODS: Effects of HGF on cell invasion and motility were
      investigated in two human CCA cell lines, HuCCA-1 and KKU-M213, using Transwell
      in vitro assay. Levels of proteins of interest and their phosphorylated forms
      were determined by Western blotting. Localization of E-cadherin was analyzed by
      immunofluorescence staining and visualized under confocal microscope. Activities
      of matrix degrading enzymes were determined by zymography. RESULTS: Both CCA cell
      lines expressed higher Met levels than the H69 immortalized cholangiocyte cell
      line. HGF induced invasion and motility of the cell lines and altered E-cadherin
      from membrane to cytoplasm localization, but did not affect the levels of
      secreted matrix metalloproteinase (MMP)-2, MMP-9 and urokinase plasminogen
      activator, key matrix degrading enzymes involved in cell invasion. Concomitantly,
      HGF stimulated Akt and extracellular signal-regulated kinase (ERK)1/2
      phosphorylation but with slightly different kinetic profiles in the two cell
      lines. Inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway by the PI3K
      inhibitor, LY294002, markedly suppressed HGF-stimulated invasion of both CCA cell
      lines, and inhibition of the ERK pathway by U0126 suppressed HGF-induced invasion
      of the KKU-M213 cell line but had a moderate effect on HuCCA-1 cells. CONCLUSION:
      These data indicate that HGF promotes CCA cell invasiveness through dys
      localization of E-cadherin and induction of cell motility by distinct signaling
      pathways depending on cell line type.

PMID- 20135720
TI  - Endoscopic findings and clinicopathologic characteristics of colonic
      schistosomiasis: a report of 46 cases.
AB  - AIM: To make a retrospective analysis of endoscopy findings and clinicopathologic
      characteristics of colonic schistosomiasis in order to further improve our
      understanding of the disease and decrease its misdiagnosis. METHODS: Endoscopy
      findings and clinicopathologic characteristics of 46 intestinal schistosomiasis
      patients were retrospectively analyzed. All the patients underwent colonoscopy
      and all biopsy specimens stained with hematoxylin and eosin were observed under a
      light microscope. RESULTS: Of the 46 colonic schistosomiasis patients, 1 was
      diagnosed as acute schistosomal colitis, 16 as chronic schistosomal colitis and
      29 as chronic active schistosomal colitis according to their endoscopic findings
      and pathology. Not all patients were suspected of or diagnosed as colonic
      schistosomiasis. Of the 12 misdiagnosed patients, 4 were misdiagnosed as
      ulcerative colitis, 1 as Crohn's disease, and 7 as ischemic colitis. The segments
      of rectum and sigmoid colon were involved in 29 patients (63.0%). Intact
      Schistosoma ova were deposited in colonic mucosa accompanying infiltration of
      eosinocytes, lymphocytes, and plasma cells in acute schistosomal colitis
      patients. Submucosal fibrosis was found in chronic schistosomal colitis patients.
      Among the 17 patients with a signal polyp, hyperplastic polyp, canalicular
      adenoma with a low-grade intraepithelial neoplastic change, tubulovillous adenoma
      with a high-grade intraepithelial neoplastic change were observed in 10, 5, and 2
      patients, respectively. Eight out of the 46 patients were diagnosed as colonic
      carcinoma. CONCLUSION: Endoscopy contributes to the diagnosis of colonic
      schistosomiasis although it is nonspecific. A correct diagnosis of colonic
      schistosomiasis can be established by endoscopy in combination with its
      clinicopathologic characteristics.

PMID- 20135721
TI  - Endoscopic ultrasound-guided celiac plexus neurolysis using a reverse phase
      polymer.
AB  - AIM: To assess the feasibility of endoscopic ultrasound (EUS)-guided celiac
      plexus neurolysis (CPN) using a poloxamer. METHODS: In this prospective
      evaluation, six Yorkshire pigs underwent EUS-guided CPN. Three received an
      injection of 10 mL of 0.25% Lidocaine plus methylene blue (group 1) and three
      received an injection of 10 mL of 0.25% Lidocaine plus blue colored poloxamer
      (PS137-25) (group 2). Necropsy was performed immediately after the animals were
      sacrificed. The abdominal and pelvic cavities were examined for the presence of
      methylene blue and the blue colored poloxamer. RESULTS: EUS-guided CPN was
      successfully performed in all 6 pigs without immediate complication. Methylene
      blue was identified throughout the peritoneal and retroperitoneal cavity in group
      1. The blue colored poloxamer was found in the retroperitoneal cavity immediately
      adjacent to the aorta, in the exact location of the celiac plexus in group 2.
      CONCLUSION: EUS-guided CPN using a reverse phase polymer in a non-survival
      porcine model was technically feasible. The presence of a poloxamer gel at the
      site of the celiac plexus at necropsy indicates a precise delivery of the
      neurolytic agent.

PMID- 20135722
TI  - ABCG5-positivity in tumor buds is an indicator of poor prognosis in node-negative
      colorectal cancer patients.
AB  - AIM: To analyze the expression of 8 putative cancer stem cell (CSC) markers
      within colorectal cancer tumor buds and to determine their prognostic impact in
      patients with this disease. METHODS: Immunohistochemistry was performed on 101
      colorectal cancer resections for CK22 (to identify tumor buds) as well as CD133,
      CD166, CD24, CD44s, CD90, EpCAM, ALDH1, and ABCG5, and their expression within
      tumor buds was evaluated. RESULTS: CD90, CD44s, and CD133 expression in tumor
      buds was found in less than 5% of all cases. ALDH1, CD24, CD166 were expressed in
      16.5%, 16.2%, and 34% cases, respectively, while ABCG5 and EpCAM expression was
      more frequent and found in 35% and 69% of cases, respectively. Of the 8 markers
      studied, EpCAM and ABCG5 positivity in tumor buds were significantly associated
      with poor prognosis (P = 0.023, P = 0.038, respectively) in multivariable
      analysis with pT and pN classification [P = 0.048; hazard ratio (HR): 2.64; 95%
      CI: 1.0-6.9, for EpCAM and P = 0.029; HR: 2.22; 95% CI: 1.0-4.5, for ABCG5]. Poor
      survival time was particularly striking for lymph node-negative patients with
      ABCG5-positive buds (P < 0.001). CONCLUSION: Expression of putative stem cell
      markers EpCAM and ABCG5 within the tumor buds of colorectal cancer are frequently
      noted and are associated with poor prognosis.

PMID- 20135723
TI  - Pericardiocentesis with cisplatin for malignant pericardial effusion and
      tamponade.
AB  - AIM: To evaluate the role and outcome of pericardiocentesis with intrapericardial
      cisplatin instillation for malignant pericardial effusion resulting from
      esophageal cancer. METHODS: We retrospectively studied 7 patients who underwent
      pericardiocentesis with intrapericardial cisplatin instillation for malignant
      pericardial effusion resulting from esophageal cancer. After pericardiocentesis,
      we performed catheterization of the pericardial space under ultrasonogram
      guidance. Malignant etiology of the pericardial fluid was confirmed by
      cytological examination. Subsequently, cisplatin (10 mg in 20 mL normal saline)
      was instilled into the pericardial space. RESULTS: The mean total volume of the
      aspirated effusion fluid was 782 +/- 264 mL (range, 400-1200 mL). The drainage
      catheter was successfully removed in all patients, and the mean duration of
      pericardial drainage was 7.7 +/- 2.7 d (range, 5-13 d). No fluid reaccumulation
      was observed. Mean survival time was 120 +/- 71 d (range, 68-268 d). CONCLUSION:
      Pericardiocentesis along with catheter drainage appears to be a safe and
      effective for pericardial malignant effusion and tamponade, and cisplatin
      instillation prevents recurrence.

PMID- 20135724
TI  - Surgery for gastrointestinal malignant melanoma: experience from surgical
      training center.
AB  - AIM: To characterize clinical features, surgery, outcome, and survival of
      malignant melanoma (MM) of the gastrointestinal (GI) tract in a surgical training
      center in Bangkok, Thailand. METHODS: A retrospective review was performed for
      all patients with MM of the GI tract treated at our institution between 1997 and
      2007. RESULTS: Fourteen patients had GI involvement either in a metastatic form
      or as a primary melanoma. Thirteen patients with sufficient data were reviewed.
      The median age of the patients was 66 years (range: 32-87 years). Ten patients
      were female and three were male. Seven patients had primary melanomas of the anal
      canal, stomach and the sigmoid colon (5, 1 and 1 cases, respectively). Seven
      patients underwent curative resections: three abdominoperineal resections, two
      wide local excisions, one total gastrectomy and one sigmoidectomy. Six patients
      had distant metastatic lesions at the time of diagnosis, which made curative
      resection an inappropriate choice. Patients who underwent curative resection
      exhibited a longer mean survival time (29.7 mo, range: 10-96 mo) than did
      patients in the palliative group (4.8 mo, P = 0.0006). CONCLUSION: GI MM had an
      unfavorable prognosis, except in patients who underwent curative resection (53.8%
      of cases), who had a mean survival of 29.7 mo.

PMID- 20135725
TI  - Effects of in vitro cultivated Calculus Bovis compound on pulmonary lesions in
      rabbits with schistosomiasis.
AB  - AIM: To explore the interventional effects and mechanism of in vitro cultivated
      Calculus Bovis compound preparation (ICCBco) on pulmonary lesions in portal
      hypertensive rabbits with schistosomiasis. METHODS: The experimental group
      included 20 portal hypertensive rabbits with schistosomiasis treated by ICCBco.
      The control group included 20 portal hypertensive rabbits with schistosomiasis
      treated by praziquantel. The morphological changes of the pulmonary tissues were
      observed under light and electron microscopy. The expression of fibronectin (FN)
      and laminin (LN) in the lung tissues was analyzed by immunohistochemistry.
      RESULTS: Under light microscope, the alveolar exudation in the lung tissue was
      more frequently observed in the control group, while the alveolar space was
      fairly dry in the lung tissue of ICCBco group. Under electron microscope, more
      alveolar exudation in the lung tissue, and more macrophages, alveolar
      angiotelectasis and the blurred three-tier structure of alveolar-capillary
      barrier could be seen in the control group. In ICCBco group, fibers within the
      alveolar interspace slightly increased in some lung regions, and the structure of
      type I epithelium, basement membrane and endodermis was complete, and no obvious
      exudation from the alveolar space, and novascular congestion could be observed.
      There was a positive or strong positive expression of FN and LN in the lung
      tissue of the control group, while there was a negative or weak positive
      expression of FN and LN in ICCBco group. CONCLUSION: ICCBco can effectively
      prevent pulmonary complications in portal hypertensive rabbits with
      schistosomiasis by means of improving lung microcirculation and lowering the
      content of extracellular matrix.

PMID- 20135726
TI  - Methylation of Dickkopf-3 as a prognostic factor in cirrhosis-related
      hepatocellular carcinoma.
AB  - AIM: To investigate the prevalence and time of Dickkopf (DKK) family methylation
      and its clinical significance in hepatocarcinogenesis. METHODS: Methylation of
      DKK family genes was quantitatively analyzed in 115 liver tissue samples,
      including 50 pairs of primary hepatocellular carcinoma (HCC) and matched
      noncancerous cirrhotic tissue samples, as well as 15 liver cirrhosis biopsy
      samples. RESULTS: The methylation level of DKK3 was significantly higher in HCC
      tissue samples than in matched noncancerous cirrhotic tissue samples (P < 0.0001)
      or in liver cirrhosis biopsy samples (P = 0.0139). Receiver operator
      characteristic curve analysis confirmed that the percent of methylated reference
      (PMR) values of DKK3 could effectively discriminate HCC tissue samples from
      noncancerous tissue samples (AUC = 0.8146) or liver cirrhosis biopsy samples (AUC
      = 0.7093). Kaplan-Meier survival curves revealed that the progression-free
      survival time of patients with a higher DKK3 methylation level (PMR > 1%) was
      significantly shorter than that of those with a lower DKK3 methylation level (PMR
      < or = 1%) (P = 0.0255). Multivariate Cox analysis indicated that methylated DKK3
      was significantly and independently related with a shorter survival time
      (relative risk = 2.527, 95% CI: 1.063-6.008, P = 0.036) of HCC patients.
      CONCLUSION: Methylation of DKK3 is an important event in early malignant
      transformation and HCC progression, and therefore might be a prognostic indicator
      for risk assessment of HCC.

PMID- 20135727
TI  - Therapy and prognostic features of primary clear cell carcinoma of the liver.
AB  - AIM: To clarify the therapeutic strategies and prognosis factors of primary clear
      cell carcinoma of the liver (PCCCL). METHODS: The clinical pathological data of
      64 patients with PCCCL treated with hepatectomy in our hospital from January 2000
      to January 2006 were analyzed retrospectively. The patients were divided into two
      groups to make treatment analysis: curative resection only (n = 40); and curative
      resection and postoperative chemotherapy with calcium folinate and tegafur (n =
      24). Meanwhile, the PCCCL patients were subdivided into two subgroups on the
      basis of the proportion of clear cells in the tumor for pathological analysis.
      There were 36 cases in subgroup A for which the proportion of clear cells was
      more than 70%, and 28 cases in subgroup B for which the proportion was less or
      equal to 70%, comparing analysis of median survival time of the counterpart
      groups. Univariate and multivariate analyses were performed to examine factors
      that affected clinical prognosis, recurrence and metastasis. RESULTS: Median
      survival period of the curative surgery group was 38 mo, while the counterpart
      was 41 mo. Median survival period for group A was 41 mo, while group B was 19 mo.
      The Kaplan-Meier method showed that capsule formation, preoperative liver
      function, hepatitis C virus infection, large vascular invasion and multiple tumor
      occurrences were related to disease-free survival. Cox regression analysis showed
      that the clear cell ratio, capsule formation, preoperative liver function and
      large vascular invasion were independent risk factors for overall survival.
      CONCLUSION: Postoperative chemotherapy has no obvious effect on survival of
      patients with PCCCL. Clear cell ratio, capsule formation, preoperative liver
      function, and vascular invasion were independent risk factors for prognosis.

PMID- 20135728
TI  - Treatment of hepatitis B virus-associated glomerulonephritis: a meta-analysis.
AB  - AIM: To evaluate the efficacy of antiviral or corticosteroid treatment on
      hepatitis B virus-associated glomerulonephritis (HBV-GN). METHODS: Six and five
      trials were used respectively to evaluate the efficacy of either antiviral or
      corticosteroid treatment on HBV-GN. Pediatric patients were pooled separately to
      assess their response to the above treatment modalities. The primary and
      secondary outcomes were remission of proteinuria and clearance of Hepatitis B e
      antigen (HBeAg), respectively. A fixed or random effect model was established to
      collect the data. RESULTS: The remission rate of proteinuria (RR = 1.69, 95% CI:
      1.08-2.65) and the clearance rate of HBeAg (RR = 6.44, 95% CI: 3.11-13.35) were
      significantly higher in antiviral treatment group than in control group. The
      proteinuria remission was significantly associated with HBeAg clearance (P =
      0.002). However, the difference in proteinuria remission rate was not
      statistically significant between corticosteroid treatment group and control
      group (RR = 1.45, 95% CI: 0.68-3.11). Antiviral therapy could significantly
      promote the HBeAg clearance in pediatric patients, but neither antiviral nor
      corticosteroid therapy could significantly decrease proteinuria in pediatric
      patients compared to controls. CONCLUSION: Antiviral but not corticosteroid
      treatment can decrease proteinuria and promote HBeAg clearance in HBV-GN
      patients.

PMID- 20135729
TI  - A case of gouty arthritis following percutaneous radiofrequency ablation for
      hepatocellular carcinoma.
AB  - Percutaneous radiofrequency thermal ablation (RFA) is considered an effective
      technique for providing local control in the majority of Hepatocellular carcinoma
      (HCC) patients. Although RFA is generally well tolerated, recent studies have
      reported complications associated with RFA. We describe a case of acute gouty
      arthritis in a 71-year-old man with chronic renal failure who was treated with
      RFA for a HCC lesion and who had hepatitis B-associated cirrhosis and mild renal
      insufficiency. Regular surveillance of the patient detected a 3.5 cm HCC lesion.
      Because the patient had declined surgery, RFA was chosen for therapy. On the
      third post-procedural day, the laboratory results showed increases in his uric
      acid and potassium levels, which were compatible with a tumor lysis syndrome. On
      the 6th post-procedural day, the patient complained of new right knee pain.
      Subsequent joint aspiration revealed monosodium urate monohydrate crystals. We
      made the diagnosis of acute gouty arthritis arising from tumor lysis and liver
      infarction caused by HCC ablation, which was aggravated by acute renal
      insufficiency. After adequate hydration and administration of oral colchicines,
      the patient's right knee pain subsided and the uric acid serum level returned to
      normal. This is the first described case of acute gouty arthritis after RFA for a
      HCC lesion in a patient with underlying chronic renal insufficiency. To avoid
      hyperuricemia and an acute attack of gout after RFA therapy for HCC, early
      identification of patients at risk is warranted, such as those with a large
      tumor, rapid tumor growth, and renal insufficiency, and preventative measures
      should be considered.

PMID- 20135730
TI  - Multiple chronic non-specific ulcer of small intestine characterized by anemia
      and hypoalbuminemia.
AB  - A female patient with anemia and hypoalbuminemia was admitted to our hospital due
      to an over 20-year history of recurrent dizziness, fatigue and ankle edema. She
      was diagnosed as multiple chronic non-specific ulcer of the small intestine
      characterized by non-specific histology and persistent gastrointestinal bleeding.

PMID- 20135731
TI  - Meta-analysis of capsule endoscopy in patients diagnosed or suspected with
      esophageal varices.
AB  - The PillCam ESO (Given Imaging, Israel) or esophageal capsule endoscopy (ECE) is
      a novel technique used in the diagnostic evaluation of esophagus. Many studies
      have been performed to compare the accuracy of ECE against the current gold
      standard esophago-gastro-duodenoscopy and a meta-analysis recently published by
      Lu et al suggests that ECE may have an acceptable sensitivity and specificity in
      detecting esophageal varices. We would like to discuss the importance and
      implication of publication bias in this meta-analysis.

PMID- 20135732
TI  - Radioscapholunate arthrodesis - a prospective study.
AB  - The purpose of this prospective study was to evaluate pain levels, range of
      motion, patient activity and satisfaction after radioscapholunate (RSL)
      arthrodesis. This was in association with distal scaphoid excision and complete
      resection of the triquetrum. The non-union rate for radioscapholunate arthrodesis
      was examined and the results compared with previous studies. Twenty-three
      patients (14 males and nine females) with an average age of 47 (range 26-73)
      years underwent RSL fusion for post-traumatic osteoarthritis, rheumatoid
      arthritis and Kienbock's disease of the lunate with a mean follow-up of 32 (range
      13-70) months. The absolute prerequisite for any of these groups of patients was
      a functional midcarpal joint which was assessed pre-operatively with radiographs
      and intra-operatively prior to RSL fusion. The average flexion to extension
      motion changed from 66 degrees to 57 degrees . The ulnoradial range of motion
      also increased to 43 degrees from a pre-operative value of 22 degrees . The
      patients visual analogue pain scores reduced from an average of 64 to 28 (p =
      0.01). Nineteen patients had no restriction in activity and all but one was
      satisfied with the outcome. All patients remained in full time employment with
      ten returning to some form of sport. RSL fusion with excision of the distal pole
      of the scaphoid and the entire triquetrum led to minimal reduction in the flexion
      extension arc of motion and an increase in the ulnoradial arc. There was also
      good pain relief and maintenance of a patient's function. Memory staples are also
      an effective method of securing fusion in the wrist obtaining similar results to
      that seen in forefoot surgery.

PMID- 20135733
TI  - A modified technique of interpositional arthroplasty in treating the Basal joint
      arthritis of the thumb in a Chinese population.
AB  - We performed a retrospective review of 22 thumbs in 22 Chinese patients attending
      for the basal joint arthritis of the thumb over the last 14 years. There were 16
      women and six men with a mean age of 50 years old. All were treated surgically by
      partial trapeziectomy and volar oblique ligament reconstruction with flexor carpi
      radialis tendon and interpositional arthroplasty with a free palmaris longus
      tendon ball after failure of conservative treatment. The mean follow-up time was
      48 months. Radiographs did not show any differences in the arthroplasty space
      index, arthroplasty space, trapezial space ratio and scaphoid-thumb metacarpal
      distance at the pre-operative evaluation and at the final follow-up evaluation.
      There was significant difference in the pain score, grip strength, Kapandji score
      and functional status before and after surgery at final follow-up period. One
      patient had complex regional pain syndrome which was resolved after receiving a
      course of anti-inflammatory drugs and physiotherapy. The authors suggest that the
      modified technique of partial trapeziectomy with tendon interpositional
      arthroplasty is a safe and effective method in treating basal joint arthritis of
      the thumb with good short term functional and radiological outcomes and minimal
      complication.

PMID- 20135734
TI  - The prognosis of fasciectomy for abductor digiti minimi and pretendinous cords in
      Dupuytren's disease of the little finger.
AB  - Thirty-nine consecutive patients with little finger Dupuytren's contracture
      underwent open fasciectomy. Diseased abductor digiti minimi (ADM) pretendinous
      (PT) cords were identified. The mean pre-operative PIPJ contracture was 77
      degrees in the PT group and 66 degrees in the ADM group. Mean residual deformity
      was 12 degrees in the PT group and 9 degrees in the ADM group. At six months, ten
      out of 27 patients had developed a recurrent deformity in the PT group (mean 24
      degrees ) and seven out of 11 in the ADM group (mean 18 degrees ). There was no
      statistically significant difference between the two groups at any stage.
      Dupuytren's contracture of the little finger is as a result of an ADM cord in 29%
      of cases. In this series it led to an isolated contracture of the PIPJ in the
      majority of cases and rarely affected the MCPJ. Disease of the ADM cord was not
      associated with a difference in contracture or prognosis compared to a PT cord.

PMID- 20135735
TI  - A new variable angled locking volar plate system for Colles' fracture: outcome
      study and time-course improvement of objective clinical variables.
AB  - Our purposes were to report the radiographic outcomes and complications of
      patients with Colles' fracture treated with the Nakashima locking volar plate
      system (variable angled distal screw locking mechanism) prospectively and to
      report the results of objective clinical variables such as grip strength and
      range of motion of the wrist prospectively at up to one year. This study
      consisted of eight men and 32 women for analysis of radiographic parameters
      (volar tilt, radial inclination and radial length) and complications.
      Radiographic parameters were measured pre-operatively, immediately post
      operatively and at final follow-up visit. The average age at operation was 60.3
      years old. Among them, we selected 25 cases (6 men and 19 women) whom we followed
      up at six weeks, three months, six months and one year post-operatively. The
      average age at operation in this group was 62 years old. We measured objective
      clinical variables (grip strength, forearm rotation, wrist extension/flexion) at
      each visit. Except for volar tilt, radiographic parameters revealed no
      significant changes between immediately post-operative radiographs and
      radiographs at final follow-up visit. Complications included loss of reduction in
      two cases. Objective clinical variables other than pronation measurement showed
      significant increase at each visit up to one year post-operatively. Satisfactory
      clinical and radiographic results were obtained by using this system. The
      variable angled distal fragment plating system appears to be a reliable construct
      for rigid fixation of Colles' fractures; however, technical errors can occur, as
      with other fixation systems. We demonstrated that the follow-up of Colles'
      fracture treated by our volar locking plate less than one year post-operative may
      be insufficient.

PMID- 20135736
TI  - Medium-term outcome following intra-articular corticosteroid injection in first
      CMC joint arthritis using fluoroscopy.
AB  - First carpometacarpal joint osteoarthritis (1(st) CMCJ OA) is a common condition
      with variable results reported from local corticosteroid injection. This study
      aims to explore the medium-term outcome with respect to pain relief, patient
      satisfaction and the need for subsequent surgical intervention. A prospective
      review was performed of patients undergoing fluoroscopically guided
      corticosteroid injection by one surgeon, with postal questionnaires for medium
      term follow-up. Forty-one patients were included. Thirty-one were female and ten
      male, with a mean age of 60 years. In the short term 76% of patients reported
      pain relief with an average duration of four weeks and 69% of the patients
      reported benefit from injection. After a median follow-up of 36 months 76% of
      patients reported continuing pain but 59% reported satisfaction with the outcome.
      Twenty-eight per cent of the patients had undergone surgery. Local corticosteroid
      injection of the CMCJ provides only short-term pain relief, but few patients go
      on to surgical intervention.

PMID- 20135737
TI  - Investigation of radiolunate relations in normal and fractured wrists.
AB  - As the distal radius fracture is one of the most commonly encountered upper limb
      injuries, the aim of this study was to provide a quick and easy method to aid in
      the assessment of fractured wrists, both pre- and post-fixation, by utilising the
      relationship of the radial shaft and the lunate. A retrospective analysis on 100
      consecutive patients with normal wrist radiographs was performed. The results
      demonstrated that the variations of radiolunate anatomy followed a normal
      distribution. The normal anatomical relationship was then described. A second
      part to the study consisted of reviewing our method of radiocarpal analysis on a
      cohort of patients who had sustained a distal radius fracture. Carpal alignment
      pre- and post-fixation was measured, with the results demonstrating that by using
      this assessment method, it was possible with a quick glance of the radiograph, to
      determine whether satisfactory correction of the fracture had been achieved.

PMID- 20135738
TI  - Percutaneous pinning of the displaced volar plate avulsion fracture of the PIP
      joint.
AB  - The use of operative or non-operative techniques in the treatment of a volar
      plate avulsion fracture of the PIP joint has remained controversial. In this
      study, we describe the use of percutaneous K-wire fixation in 15 patients with a
      displaced and rotated large fragment of this injury. All processes of the
      technique, including reduction and interfragmental fixation, were performed with
      percutaneous K-wires. Mean follow-up was 14.2 months. All patients achieved bony
      union. Mean active motion was -1.3 degrees /86.2 degrees for the PIP joint and 0
      degrees /77.5 degrees for the DIP joint and mean %TAIM was 94.6%. There were no
      complications. No patients complained of pain and all were able to return to
      their previous activity. Although this procedure is technically demanding, it
      reconstructs a rotated or displaced large volar plate avulsion with a low level
      of invasion, and achieves a satisfactory functional recovery.

PMID- 20135739
TI  - Atypical glomus tumour of the wrist: a case report.
AB  - Wrist glomus tumours are extremely rare. We report a case of an unusually large
      wrist glomus tumour with atypical presentation. Magnetic resonance imaging (MRI)
      findings correlated well to those previously described for digital glomus
      tumours. This rare differential should be considered when evaluating lesions
      around the wrist.

PMID- 20135740
TI  - Lengthening the locking loop repair for zone 2 flexor tendon laceration and
      partial lateral release of the tendon sheath.
AB  - The authors present the clinical outcomes of nine zone 2 flexor tendon repairs
      using a locking loop technique (i.e. the Modified Pennington technique). The
      locking loops were located approximately 10 mm away from the lacerated tendon
      ends to "lengthen" the locking loop repair, as experimentally and clinically
      recommended. The partial lateral release of the tendon sheath, including the A2
      and/or A4 pulley, was performed not only to locate the sutures but also to allow
      a full range of motion of the repair without catching on the tendon sheath, as
      clinically recommended. All the patients were followed up for six months or more
      except for one. All digits were evaluated as excellent or good at the final
      follow-up by the original Strickland criteria. No rupture occurred and no
      bowstring of the flexor tendon was observed. The clinical outcomes of the current
      study indicate that "lengthening" the locking loop repair is effective for zone 2
      flexor tendon repair and that the partial lateral release of the tendon sheath,
      including the A2 and/or A4 pulley, does not result in the bowstring of the flexor
      tendon.

PMID- 20135741
TI  - An uncommon cause for a common complaint.
AB  - Infective tenosynovitis is an uncommon cause of a common condition namely carpal
      tunnel syndrome. Following an extensive review of the literature, we report what
      we understand to be the first published case of Mycobacterium kansasii (M.
      kansasii) causing tenosynovitis of flexor tendons resulting in carpal tunnel
      syndrome in Australia. Our case highlights the need for a high level of
      suspension, histology and appropriate culture with specific microbiological tests
      for atypical mycobacteria where tenosynovitis is present at carpal tunnel
      surgery, even in patients who do not appear to have risk factors.

PMID- 20135742
TI  - Bilateral rupture of the extensor pollicis longus tendon in a professional
      goalkeeper following steroid injections for extensor tenosynovitis.
AB  - We present a rare case of bilateral extensor pollicis longus tendon rupture in a
      professional football goalkeeper following steroid injection for extensor
      tenosynovitis. The potential pathogenesis mechanisms are discussed.

PMID- 20135743
TI  - Closed flexor pulley rupture of the thumb: case report and review of literature.
AB  - Closed flexor pulley rupture of the thumb is extremely rare. We report a case
      with this condition. The anatomic and biomechanical studies, clinical and
      operative finding as well as the management of the closed flexor pulley rupture
      of the thumb are discussed.

PMID- 20135744
TI  - Multiple simultaneous mallet fingers in goalkeeper.
AB  - The mallet finger is a common hand injury in sports with ball use. Here, we
      present the case of a goalkeeper with simultaneous bilateral mallet fingers in
      the third and fourth ray, successfully treated with splinting. Origin and
      treatment options are discussed.

PMID- 20135745
TI  - Apparent visi deformity: periscaphoid perilunate dissociation - a case report.
AB  - We report a case of carpal instability complex, which presented apparent volar
      intercalated segmental instability (VISI) caused by acute injury. Proper
      diagnosis and treatment by ligament repair and Kirschner wire fixation yielded
      good clinical results.

PMID- 20135746
TI  - Unusual pattern of dislocation of the trapeziometacarpal joint with avulsion
      fracture of the trapezium: case report.
AB  - Dislocation of the trapeziometacarpal joint is a rare injury. We report an
      unusual pattern of dorsal dislocation of the trapeziometacarpal joint with an
      avulsion fracture of the dorsoradial tubercle of the trapezium. Simultaneous
      ligament rupture with an avulsion fracture of the thumb metacarpophalangeal joint
      was associated. The trapeziometacarpal joint was reduced and disrupted ligaments
      with avulsed fragments of both joints were surgically repaired.

PMID- 20135747
TI  - India failing children orphaned by AIDS.

PMID- 20135749
TI  - Avoiding hypothermia, an intervention to prevent morbidity and mortality from
      pneumonia in young children.
AB  - Observations and experiments in animals and human beings grant plausibility to
      the hypothesis that hypothermia is a risk factor for pneumonia. Exposure of body
      to cold stress causes alterations in the systemic and local defenses against
      respiratory infections, favoring the infection by inhalation of pathogens
      normally present in the oropharynx. Neonates and young infants with hypothermia
      have an increased risk of death; however, there is no strong demonstration that
      hypothermia leads to pneumonia in these children. Studies that properly addressed
      the problem of confounding variables have shown an association between cold
      weather and pneumonia incidence. Probably the strongest evidence that supports
      the plausibility of the hypothesis is provided by the controlled comparison
      between patients with traumatic brain injury treated with hypothermia and those
      treated under normal body temperature. The association between exposure to cold
      and pneumonia is strong enough to warrant further research focused in young
      children in developing countries.

PMID- 20135748
TI  - Probiotics have clinical, microbiologic, and immunologic efficacy in acute
      infectious diarrhea.
AB  - BACKGROUND: Acute infectious diarrhea is a major cause of childhood morbidity and
      economic burden for families. We evaluate the clinical, microbiologic, and
      immunologic effects of probiotics in acute infectious diarrhea. METHODS: Children
      (n = 304) aged 3 months to 6 years hospitalized for acute diarrhea were
      randomized to receive Bio-three (a mixture of Bacillus mesentericus, Enterococcus
      faecalis, and Clostridium butyricum) or placebo orally 3 times daily for 7 days.
      Fecal samples were homogenized for bacterial culture and blood cells were
      isolated for cell culture and cytokine analysis. This study is registered
      (NCT00463190). RESULTS: The mean duration of diarrhea after start of therapy was
      60.1 hours in the probiotics group versus 86.3 hours in the placebo group (P =
      0.003). Hospital stay was shorter in the probiotics group than in the placebo
      group (P = 0.009). Counts of Bifidobacteria and Lactobacillus species were
      elevated in stool culture of the probiotics (Bio-three) group. IL-10 was
      increased in the serum and supernatants of cell culture in the probiotics group,
      and tumor necrosis factor-alpha values were down-regulated. Interferon- gamma and
      IL-12 were mildly elevated in the probiotics group, compared with the placebo
      group. CONCLUSIONS: This probiotics mixture reduced the severity of diarrhea and
      length of hospital stay in children with acute diarrhea. In addition to restoring
      beneficial intestinal flora, probiotics may enhance host protective immunity such
      as down-regulation of pro-inflammatory cytokines and up-regulation of anti
      inflammatory cytokines.

PMID- 20135750
TI  - Seasonal trend and serotype distribution of rotavirus infection in Japan, 1981
      2008.
AB  - A total of 10,917 fecal specimens from infants and children with gastroenteritis
      in seven different regions of Japan in the last 3 decades were examined for
      rotavirus. We observed that the rotavirus peak shifted gradually from January to
      April (winter to early spring) during 17 seasons and the G1P[8] combination was
      the most predominant genotype in the last 28 years in Japan.

PMID- 20135751
TI  - Burden of childhood rotavirus disease on health systems in the United States.
AB  - BACKGROUND: To determine the burden of rotavirus disease before the introduction
      of rotavirus vaccines. METHODS: From February 2005 to June 2006, prospective
      rotavirus surveillance was conducted in Cincinnati, Ohio, and Durham, North
      Carolina. Children < 5 years of age presenting at hospitals and outpatient
      clinics with acute gastroenteritis (AGE) of < 72 hours duration were enrolled.
      Stool samples were first tested for rotavirus by EIA and the VP7 type was
      determined by RT-polymerase chain reaction for rotavirus-positive samples.
      Medical costs were obtained from billing or accounting data. RESULTS: A total of
      1998 children were enrolled, with a mean age of 16.9 months. Among 1601 (80%)
      patients with a stool specimen, 44% were rotavirus positive. The rotavirus
      detection rate was 38% for patients admitted to hospital, 60% for patients
      requiring a short-stay hospital visit (< 24 hour hospitalization), 49% for
      emergency department visits, and 37% for outpatient visits. During the rotavirus
      season, rotavirus accounted for 56% of all AGE cases. Only 11% of rotavirus
      positive children were assigned the rotavirus-specific ICD-9-CM code and this
      proportion varied considerably by clinical setting. The VP7 genotypes identified
      were G1, 79%; G2, 14%; G3, 5%; G9, 1%; and G12, 1%. For children hospitalized
      with rotavirus, the estimated median direct cost was $4565, the average length of
      stay was 1.9 days, and parents lost 3.4 days of work. For short-stay, emergency
      department, and outpatient visits, the estimated median costs were $3160, $867,
      and $75, respectively. CONCLUSIONS: Before the widespread use of rotavirus
      vaccines in the United States, rotavirus was prevalent among children treated in
      hospital-based and outpatient settings and was associated with a substantial
      proportion of pediatric medical visits for AGE.

PMID- 20135752
TI  - Might platelet-leucocyte complexes be playing a role in major vascular
      involvement of Behcet's disease? A comparative study.
AB  - We determined platelet-leucocyte complexes, which play roles in the thrombosis
      inflammation relationship, in Behcet's disease patients with and without major
      vascular involvement (MVI) and in healthy controls. We included 36 Behcet's
      disease patients (22 male, 14 female, mean age: 34.4 +/- 8.3 years) and 20
      healthy individuals (14 male, six female, mean age: 31.8 +/- 4.4 years). Whole
      blood count, CRP and ESR were determined in both groups. Clinical data about the
      patients were obtained from medical charts. Individuals with hypertension,
      diabetes, coronary artery disease, and smokers were excluded. Behcet's disease
      patients with MVI were taken as a separate group (8 male, 5 female, mean age: 37
      +/- 8 years). MVI was defined as the presence of pulmonary arterial aneurysm,
      deep venous thrombosis, vena cava inferior or superior thrombosis, or venous
      sinus thrombosis. Flow cytometry was used to determine platelet-monocyte
      complexes (PMC), platelet-neutrophil complexes (PNC), basal and adenosine
      diphosphate (ADP)-stimulated platelet CD62P expression. Behcet's disease patients
      with MVI had significantly higher PNC than Behcet's disease patients without MVI
      and healthy controls (P values = 0.01). PMC levels in Behcet's disease patients
      with MVI were significantly higher than in healthy controls (P = 0.01). The
      groups were similar in basal and ADP-stimulated platelet CD62P expression (P
      values >0.05). Basal and ADP-stimulated CD62P expression, PMC and PNC were not
      significantly different between active Behcet's disease versus inactive Behcet's
      disease patients. The evaluated parameters were similar in Behcet's disease
      patients with and without uveitis, and pathergy-positive and pathergy-negative
      groups. Our results might suggest that the formation of PMC and PNC might play a
      role in thrombosis and MVI of Behcet's disease.

PMID- 20135753
TI  - Novel paediatric anticoagulants: a review of the current  literature.
AB  - There are many limitations with respect to anticoagulants currently used in
      standard paediatric practice for prophylaxis and treatment of thrombosis:
      heparin, low molecular-weight heparin, and warfarin. Factors such as
      pharmacokinetic and dosing variability are further exacerbated by properties of
      the immature haemostatic system of children. These shortcomings necessitate
      exploring alternative anticoagulants in the paediatric population. In this
      review, we discuss several promising direct thrombin inhibitors and factor Xa
      inhibitors, and synthesize relevant drug information and clinical experience from
      the limited available case reports, case series, and nonrandomized dose-finding
      trials published to date.

PMID- 20135755
TI  - Words of wisdom. Re: Comparative effectiveness of minimally invasive vs open
      radical prostatectomy.

PMID- 20135754
TI  - Words of wisdom. Re: Comparative effectiveness of minimally invasive vs open
      radical prostatectomy.

PMID- 20135756
TI  - Words of wisdom. Re: Rethinking screening for breast cancer and prostate cancer.

PMID- 20135757
TI  - Words of wisdom. Re: Radical prostatectomy findings in patients in whom active
      surveillance of prostate cancer fails.

PMID- 20135758
TI  - Words of wisdom. Re: Periprostatic adipose tissue as a modulator of prostate
      cancer aggressiveness.

PMID- 20135759
TI  - Words of wisdom. Re: Effects of simvastatin, acetylsalicylic acid, and
      rosiglitazone on proliferation of normal and cancerous prostate epithelial cells
      at therapeutic concentrations.

PMID- 20135760
TI  - Comments on prevalence of bovine tuberculosis in Minnesota.

PMID- 20135761
TI  - Reflexes, consciousness, and evolution.

PMID- 20135762
TI  - Fatigue--from muscle to brain or vice versa?

PMID- 20135763
TI  - The influence of afferent feedback, perceived exertion and effort on endurance
      performance.

PMID- 20135764
TI  - Both afferent feedback and psychobiological factors are important.

PMID- 20135765
TI  - Other sources outside the muscle afferent feedback limit locomotor performance in
      the heat.

PMID- 20135766
TI  - Differences between activities highlight the respective neuromuscular or
      psychobiological influences.

PMID- 20135767
TI  - The importance of pacing.

PMID- 20135768
TI  - Group III and IV muscle afferent feedback contribution to cardiorespiratory and
      neural adjustments.

PMID- 20135769
TI  - Afferent feedback and psychobiological components: complementary approaches.

PMID- 20135770
TI  - Sense of effort may be altered by the effects of afferent feedback on the motor
      pathway.

PMID- 20135771
TI  - Afferent muscular feedback as a determinant of exercise endurance.

PMID- 20135772
TI  - Retraction. Overexpression of pre-pro-cholecystokinin stimulates beta-cell
      proliferation in mouse and human islets with retention of islet function.

PMID- 20135773
TI  - Upstate AHEC Lateral Violence among Nurses Project.

PMID- 20135774
TI  - Making them pay. High-cost of healthcare reform is fueling more fraud
      enforcement, putting hospitals, physicians, other providers on notice.
AB  - The feds are playing hardball when it comes to healthcare fraud, and physicians
      and executives are feeling the heat, along with hospitals and systems. "Under the
      anti-kickback statute and Stark self-referral law, it takes two to tango. When
      we're doing our analysis of the fraud problem, we have come to recognize we're
      only going to get our arms around this if we address both parties to the scheme,"
      says HHS' Lewis Morris, left.

PMID- 20135775
TI  - A loss for hospitals. Senate package could negate deal with key groups.

PMID- 20135776
TI  - Sibling rivalry. House seeks to match affordability of Senate's bill.

PMID- 20135777
TI  - Patient safety, IT center stage.

PMID- 20135778
TI  - Healthcare's green shoots. Reform, quality and HIT all moving forward, but
      there's still much to do.

PMID- 20135779
TI  - Changing course. A few well-publicized cases of medical errors have led the
      hospitals involved to transform how they approach patient safety.
AB  - As family members of the victims of medical errors have launched their own
      patient-safety movement, the hospitals where those incidents occurred are making
      changes to protect against future problems. St. Luke's Boise Medical Center has
      taken a number of such steps. And it's not always easy. "When you're changing
      culture, it's overcoming history," says physician Barton Hill, left. "To do
      nothing about it is unconscionable".

PMID- 20135780
TI  - House vote imminent ... but not everyone pleased with way bill shaped up.

PMID- 20135781
TI  - Devicemakers smell victory. House, Senate have different ideas on taxes.

PMID- 20135782
TI  - The emergency's here ... now officials are wondering where the vaccine is.

PMID- 20135783
TI  - The cost of H1N1. Payers hope vaccine availability will help ease costs.

PMID- 20135784
TI  - Network, privacy revisited. Blumenthal eyes national policy for IT security.

PMID- 20135785
TI  - Privacy, please. IT Congress urge HHS to add harm threshold.

PMID- 20135786
TI  - Difficult trading. Volatile swaps complicate exiting credit deals.

PMID- 20135787
TI  - Labor tension. Employers foresee more union organizing: survey.

PMID- 20135788
TI  - Laying out our rules. Code of Ethics steers how we deliver news and information
      to you.

PMID- 20135789
TI  - Mission: Medicare. Opinion Leaders mull Medicare changes like drug price
      leverage, advisory council.

PMID- 20135790
TI  - Slow spending, improve quality. Moving from fee-for-service to integrated
      delivery key to Medicare reform.

PMID- 20135791
TI  - Don't take it for granted. Medicare reform must address most serious problem-
      inadequate benefits.

PMID- 20135792
TI  - Plump and growing. Democrats' reform bills would worsen, not tame, healthcare
      inflation.

PMID- 20135793
TI  - A fresh approach. Wisconsin hospital gives a big boost to local farm co-op as
      facilities nationwide look to nearby sources in search of a higher-quality food
      supply.

PMID- 20135794
TI  - Return to normalcy? CPI, PPI numbers return to more typical growth.

PMID- 20135795
TI  - Helping Haiti. U.S. healthcare donates, cares for patients.

PMID- 20135796
TI  - The bucks stop here for academic centers. Study shows research funding down,
      experts fear it could hinder advancements.

PMID- 20135797
TI  - Dialysis dilemma. Funding cut in Miami could affect immigrants.

PMID- 20135798
TI  - Less waiting. New Calif HMO rules call for better access in '11.

PMID- 20135799
TI  - Left out of debate. Nurses' voices not being heard on reform: study.

PMID- 20135800
TI  - Integrating success. Top-performing health networks offer lessons in using
      efficiencies, expertise to improve patient care.

PMID- 20135801
TI  - Great walls of China. Massive new hospital just one of thousands to be built in
      next several years.

PMID- 20135802
TI  - Meaningful obtuse? Experts say proposed rule might be too ambitious.

PMID- 20135803
TI  - Certification details still unknown.

PMID- 20135804
TI  - Hedge on pledge. Groups: cover more people, or let us contribute less.

PMID- 20135805
TI  - New standards to uphold. Joint Commission draft for bylaws gains traction as
      comment period continues.

PMID- 20135806
TI  - Keeping us safe. Extra attention to existing and emerging health threats is
      welcome news.

PMID- 20135807
TI  - Missing the mark. Caps hamstring victims, fail to slow rising costs of care,
      malpractice insurance.

PMID- 20135808
TI  - Reform imminent, near-term changes are not.

PMID- 20135809
TI  - Not so meaningful for some. Critical-access hospitals seek more clarity from
      feds.

PMID- 20135810
TI  - Election 2010: NHS at centre of Tories' election campaign.

PMID- 20135811
TI  - H1N1 vaccine. Four SHAs have swine flu jab deals in place.

PMID- 20135812
TI  - Burnham gets personal with tailored care drive.

PMID- 20135813
TI  - Left holding the foundation baby?

PMID- 20135814
TI  - Local decision making. Commissioning in good company.

PMID- 20135815
TI  - Mental health. An accessible answer to a huge unmet need.

PMID- 20135816
TI  - Dental treatment selection and guidance decisions for patients based upon
      economics.

PMID- 20135817
TI  - Oral pathology quiz 65. Case number 3. Odontogenic keratocyst.

PMID- 20135818
TI  - Oral pathologic quiz 65. Case number 4. Hyperplastic dental follicle.

PMID- 20135819
TI  - Massachusetts concern. If GOP wins crucial race, reform could be blocked.

PMID- 20135820
TI  - MedPAC proposes cuts. Hackbarth says 2011 cuts to 'force' efficiency.

PMID- 20135821
TI  - The new privacy police. Conn. cited as first to sue under new authority.

PMID- 20135822
TI  - Gundersen's for-profit play. Logistics Health's chief formerly on system's board.

PMID- 20135824
TI  - Ready for a resurgence. While hospital mergers and aquisitions have tailed off in
      recent years, most signs point to busier times in 2010 and beyond.

PMID- 20135823
TI  - Give us control. Physicians must direct ER staffers in fact--not just in name.

PMID- 20135825
TI  - Comparative effectiveness research stalls in the USA.

PMID- 20135826
TI  - Autonomy should chair, not rule.

PMID- 20135827
TI  - Respiratory viral RNA on toys in pediatric office waiting rooms.
AB  - BACKGROUND: Toys in pediatric office waiting rooms may be fomites for
      transmission of viruses. METHODS: Eighteen samples were taken from office objects
      on 3 occasions. Samples were tested for presence of picornavirus (either
      rhinovirus or enterovirus) on all 3 sample days; in addition, January samples
      were tested for respiratory syncytial virus and March samples were tested for
      influenza A and B. In addition, 15 samples were obtained from the sick waiting
      room before and after cleaning. Polymerase chain reaction was used to detect
      picornavirus, respiratory syncytial virus, and influenza A or B virus. Finally,
      20 samples were obtained from the fingers of a researcher after handling
      different toys in the sick waiting room, and samples were then obtained from all
      the same toys; all samples were tested for picornavirus by polymerase chain
      reaction. RESULTS: Viral RNA was detected on 11 of 52 (21%) of toys sampled. Ten
      of the positives were picornavirus; 1 was influenza B virus. Three (30%) of 10
      toys from the new toy bag, 6 of 30 (20%) in the sick child waiting room, and 2 of
      12 (17%) in the well child waiting room were positive. Six (40%) of 15 toys in
      the sick waiting room were positive for picornaviral RNA before cleaning; after
      cleaning, 4 (27%) of 15 were positive in spite of the fact that RNA was removed
      from 4 of 6 of the original positives. Three (15%) of 20 toys in the sick waiting
      room were positive for picornaviral RNA, but RNA was not transferred to the
      fingers of the investigator who handled these toys. COMMENT: About 20% of the
      objects in a pediatric office may be contaminated with respiratory viral RNA,
      most commonly picornavirus RNA. Cleaning with a disinfectant cloth was only
      modestly effective in removing the viral RNA from the surfaces of toys, but
      transfer of picornaviral RNA from toys to fingers was inefficient.

PMID- 20135828
TI  - Diagnosis of Streptococcus pneumoniae and Haemophilus influenzae type b
      meningitis by identifying DNA from cerebrospinal fluid-impregnated filter paper
      strips.
AB  - BACKGROUND: Bacterial meningitis remains often etiologically unconfirmed,
      especially in resource-poor settings. We tested the potential of real-time
      polymerase chain reaction to identify Streptococcus pneumoniae (Pnc) and
      Haemophilus influenzae type b (Hib) from cerebrospinal fluid impregnated on
      filter paper strips. METHODS: Pnc and Hib genome equivalents were blindly
      quantified by polymerase chain reaction from 129 liquid cerebrospinal fluid (CSF)
      samples-the standard-and strips stored at room temperature for months. Genome
      counts were compared by simple regression. RESULTS: The strips showed a
      sensitivity and specificity of 92% and 99% for Pnc, and of 70% and 100% for Hib,
      respectively. The positive and negative predictive values were 94% and 97% for
      Pnc, and 100% and 89% for Hib, respectively. For Pnc, the positive and negative
      likelihood ratio was 92 and 0.08, and the overall accuracy 98%, whereas for Hib
      they were 70 and 0.30, and 91%, respectively. Genome counting showed good
      correlation between the filter paper and liquid CSF samples, r(2) being 0.87 for
      Pnc and 0.68 for Hib (P < 0.0001 for both). CONCLUSION: Although not replacing
      bacterial culture, filter paper strips offer an easy way to collect and store CSF
      samples for later bacteriology. They can also be transported in standard envelops
      by regular mail.

PMID- 20135829
TI  - Prevalence and clinical and molecular characterization of human metapneumovirus
      in children with acute respiratory infection in China.
AB  - BACKGROUND: Human metapneumovirus (HMPV), a newly discovered paramyxovirus, has
      been associated with acute respiratory tract infections (ARTIs). However, the
      prevalence and molecular characteristics of HMPV in China are still unclear.
      METHODS: A total of 661 nasopharyngeal aspirates (NPA) specimens were collected
      from 661 children with ARTIs between December 2006 and November 2008. Specimens
      were screened for HMPV by reverse transcription-polymerase reaction. All positive
      amplification products were confirmed by sequencing. RESULTS: HMPV was detected
      in 45 patients (6.80%) of the 661 children. The HMPV-infected patients were from
      29 days to 9 years of age. A high incidence of HMPV infection (84.4%) was
      observed during the winter-spring season. Of the 45 HMPV-positive patients, 25
      (55.6%) were co-infected with other respiratory viruses, and respiratory
      syncytial virus (RSV) was the most common additional respiratory virus. The most
      common clinical diagnosis was bronchopneumonia (57.8%) and cough (88.9%) was the
      most common clinical symptom. Phylogenetic analysis of the F gene revealed that
      80% of the HMPV detected were A2, 2.2% were A1, and 17.8% were B1. Statistical
      analyses showed that sex, ages, seasons, and severity of the disease did not
      correlate with HMPV genotype (P = 0.986, 0.347, 0.660, 0.252), but viral
      coinfection with HMPV increased hospitalization rates (P = 0.005). CONCLUSIONS:
      HMPV was frequently detected in the pediatric patients with ARTI in China. RSV
      was the most common coinfection virus and coinfection increased hospitalization
      rates. All HMPV subgroups except B2 cocirculated and there was no association
      found between HMPV genotypes and severity of disease.

PMID- 20135830
TI  - Epidemiology of methicillin-susceptible Staphylococcus aureus in a university
      medical center day care facility.
AB  - BACKGROUND: Few data are available on methicillin-susceptible Staphylococcus
      aureus (MSSA) colonization in day care. We performed a study in a child care
      center on a medical university campus to study the epidemiology of MSSA in this
      population. METHODS: A cross-sectional study was done on 104 day care attendees
      and 32 adult employees of the child care center. Swab samples were taken from the
      nose, oropharynx, axilla, groin, and perirectal area of children, from the nose
      and oropharynx of employees, and from the environment. Parents and employees
      completed questionnaires. Swabs were placed in broth, then plated on agar and
      identified as MSSA by routine methods. Molecular typing was performed. RESULTS:
      The prevalence of MSSA was 21.15% in children and 28.13% in employees. MSSA was
      found in 8.72% of environmental samples. Univariate analysis identified 3 risk
      factors and 5 protective factors for MSSA colonization. In multivariable
      analysis, only 2 variables remained significantly related to MSSA colonization,
      with older age remaining as a risk factor and receipt of beta-lactams approaching
      significance as being protective. Many of the isolates were indistinguishable by
      molecular typing. CONCLUSIONS: The prevalence of MSSA colonization in children
      and care providers in a university medical center child care center is similar to
      that of the general population. Children colonized with MSSA tended to be older
      and to have received fewer courses of antibiotics than children who did not have
      MSSA. The relatedness of many of the isolates indicates that transmission of MSSA
      occurred at this child care center.

PMID- 20135831
TI  - Doripenem: an early look at a carbapenem not yet approved for pediatrics.

PMID- 20135832
TI  - Randomized study of the effect of topical anesthesia on tuberculin skin test
      reaction size in children.
AB  - Tuberculin skin test (TST) application in children can be eased by topical
      anesthesia, but no study has determined whether lidocaine-prilocaine mixture
      application modifies TST skin reactions. We compared TST performed with and
      without topical anesthesia in 46 children (range, 0.4-15.9 years), and found that
      topical lidocaine-prilocaine did not affect the TST size reaction. Topical
      lidocaine-prilocaine can be used for TST.

PMID- 20135833
TI  - Risk factors for recurrent urinary tract infections in a cohort of patients with
      primary vesicoureteral reflux.
AB  - BACKGROUND: Knowledge of risk of urinary tract infection (UTI) recurrence in
      vesicoureteral reflux (VUR) can help clinicians make therapeutic decisions. The
      aim of this retrospective cohort study was to identify risk factors associated
      with recurrent urinary tract infection in children with VUR. In addition, a risk
      score that might predict the chance of UTI recurrence was also proposed. METHODS:
      Between 1970 and 2007, 740 patients were diagnosed with VUR and were
      systematically followed up at a single tertiary Renal Unit. Recurrent UTI was
      defined as more than 1 episode during follow-up. A binary logistic regression
      model was applied to identify variables independently associated with recurrent
      UTIs. RESULTS: During follow-up, information was obtained on 58,856 person
      months. Recurrent UTIs occurred in 120 (16.2%) patients. The overall incidence
      rate of UTI was 8.4 episodes per 1000 person-months (95% CI, 7.7, 9.2). After
      adjustment by multivariable analysis, 5 variables were independent predictors of
      recurrent UTI: UTI as clinical presentation, age < 6 months, female gender,
      dysfunctional elimination syndrome, and severe grade of reflux. The risk for
      recurrent UTI was classified as low in 24% of children, medium in 42%, and high
      in 34%. UTI incidence rates per 1000 person-months were 4.3 (95% CI, 3.2, 5.6),
      7.9 (95% CI, 6.7, 9.1), and 11.3 (95% CI, 9.9, 12.8) for low-, medium-, and high
      risk groups, respectively. CONCLUSION: The prediction model of recurrent UTI
      allows an early recognition of patients at risk for long-term morbidity and might
      contribute to the formulation of therapeutic strategies.

PMID- 20135834
TI  - Afferent feedback from fatigued locomotor muscles is important, but not limiting,
      for endurance exercise performance.

PMID- 20135835
TI  - Psychobiological factors are more important than central fatigue in limiting
      endurance performance.

PMID- 20135836
TI  - Paradigm shift to the psychobiological model.

PMID- 20135837
TI  - Endurance exercise performance is determined by both autonomic and psychological
      factors.

PMID- 20135838
TI  - Both afferent feedback and psychobiological factors are important.

PMID- 20135839
TI  - Limitation of performance and the brain: simply more complex.

PMID- 20135840
TI  - Central fatigue is not the source but can explain performance decrement due to
      afferent feedback.

PMID- 20135841
TI  - What is this thing "fatigue" anyway?

PMID- 20135842
TI  - Afferent feedback from locomotor muscles is not restricted to group III and IV
      afferents.

PMID- 20135843
TI  - Sense of effort may be altered by the effects of afferent feedback on the motor
      pathway.

PMID- 20135844
TI  - "Traditional" perspectives can explain the sprint finish.

PMID- 20135845
TI  - Staphylococcus aureus nasal colonization among pediatric cystic fibrosis patients
      and their household contacts.
AB  - BACKGROUND: Little is known about the prevalence of Staphylococcus aureus nasal
      colonization and the epidemiology of methicillin-susceptible and methicillin
      resistant S. aureus (MRSA) among cystic fibrosis (CF) patients and their
      household members. OBJECTIVES: We sought to determine the epidemiology of S.
      aureus among children and adolescents with CF and their household members.
      METHODS: Three CF centers enrolled case subjects with at least 1 MRSA-positive
      respiratory tract culture from 2001 to 2006 and control subjects with MRSA
      negative cultures. S. aureus isolates from the anterior nares of CF subjects and
      their household members were assessed for staphylococcal chromosomal cassette
      (SCC) mec type. Strain similarity was determined by pulsed-field gel
      electrophoresis. RESULTS: S. aureus nasal colonization occurred in 52.4% (22/42),
      27.0% (17/63), and 25.0% (72/288) of case, control, and household participants,
      respectively. Case subjects and their contacts were more likely to harbor MRSA in
      their nares and be from a multipatient CF family. Of 31 MRSA strains, 10 (32.3%)
      were SCCmec type IVa, associated with community-acquisition. Overall, 27.6% of 98
      households had > or =2 members colonized with closely related isolates. Household
      members were equally likely to be colonized with closely related strains of MRSA
      (20/31, 65%) versus MSSA (38/80, 48%). CONCLUSIONS: This study demonstrated that
      household members of CF children harbor both MSSA and MRSA, including CA-MRSA,
      and that S. aureus is transmitted within CF households. Carriage of S. aureus by
      household members of CF children may have implications for infection control and
      treatment strategies. Future studies should monitor the distribution and
      virulence of SCCmecA types in patients with CF.

PMID- 20135846
TI  - Serogroup C meningococcal osteomyelitis: a case report and review of the
      literature.
AB  - A rare case of a 7-year-old boy with acute hematogenous osteomyelitis caused by
      Neisseria meningitidis serogroup C is presented. The diagnosis of osteomyelitis
      was made by bone scintigraphy and a blood culture confirmed meningococci as the
      cause of the disease. Meningococcal osteomyelitis is exceptionally rare and to
      our knowledge, serogroup C meningococci have not been previously reported as a
      cause.

PMID- 20135847
TI  - Multicentric osteoid osteoma with a nidus located  in the epiphysis.
AB  - We present a 13-year-old girl who was referred to our clinic with a 5-month
      history of right leg pain relieved by salicylates. Initial CT examination
      demonstrated a lesion in the posterior tibial cortex in keeping with an osteoid
      osteoma. This was resected and the diagnosis confirmed by histology. However, her
      pain recurred 2 weeks after the operation and further imaging identified a
      further nidus in the epiphysis. We present the imaging findings in this unique
      case of multicentric osteoid osteoma with one nidus located in the epiphysis.

PMID- 20135848
TI  - Molecular characterization and expression pattern of two zona pellucida genes in
      half-smooth tongue sole (Cynoglossus semilaevis).
AB  - Zona pellucida (ZP) proteins are glycoproteins in fish chorion that are encoded
      by multiple gene families, mainly including zp1, zp2, and zp3. In the present
      study, we cloned two zp genes of half-smooth tongue sole, Cynoglossus semilaevis,
      using reverse-transcription polymerase chain reaction (RT-PCR) and rapid
      amplification of cDNA ends (RACE). The two genes were demonstrated to belong to
      zp3 isoforms by utilizing BLAST, alignment of amino acid sequence, and
      phylogenetic analysis. The two genes were named C. semilaevis zp3a and C.
      semilaevis zp3b. C. semilaevis zp3a encoded 519 amino acid protein, including a
      signal peptide and a ZP domain with 257 amino acids, which was 62% identical to
      the medaka ZPC5. Incontrast, C. semilaevis zp3b encoded a 313 amino acid protein,
      including a signal peptide and a ZP domain with 233 amino acids, which was 63%
      identical to the medaka (Oryzias latipes) ZPC1. Alignment analysis showed that
      the ZP domain of the two ZP proteins contained eight conserved cysteines. RT-PCR
      indicated that the C. semilaevis zp3a was highly expressed in the ovary and
      kidney of females, and weakly expressed in female muscle and spleen. The C.
      semilaevis zp3b mRNA was expressed in several tissues of females,including a high
      expression level in the ovary and kidney, and a relatively low expression level
      in the heart,brain, muscle, spleen, gill, and intestine. Interestingly, the zp3b
      mRNA was slightly detected in the testis and kidney of males. Therefore,
      molecular cloning and characterization of zp genes could lay a foundation for our
      understanding of the regulation of zp gene evolution and the regulatory mechanism
      of fertilization.

PMID- 20135850
TI  - [Cuban emigration in the 1990's].

PMID- 20135853
TI  - Illegitimate sufferers: a-bomb victims, medical science, and the government.

PMID- 20135854
TI  - The consolation of botany, or the significance of the pause.

PMID- 20135855
TI  - [The development of genetics in our country in the reflections of Jan Necasek].

PMID- 20135856
TI  - [Several perspectives on alchemical transmutation].

PMID- 20135857
TI  - [The rediscovery of a scientific animal breeding school in the context of the
      origin and acceptance of Mendel's discovery].

PMID- 20135858
TI  - [Research for radiological technologist].

PMID- 20135859
TI  - [Lation in ensuring the sanitary-and-epidemiological well-being under the present
      conditions].
AB  - The paper describes the basic principles in and approaches to the state
      regulation in ensuring the sanitary-and-epidemiological well-being. The necessity
      of enhancing the role of state regulation in ensuring the sanitary-and
      epidemiological well-being stems from the intensive development of marketing
      relations and the complicated realization of the state role in the protection of
      consumers' rights and human well-being. The investigations provide evidence for
      the basic tasks of the sanitary-and-epidemiological service of Moscow under the
      specific conditions of the megalopolis.

PMID- 20135860
TI  - [The mechanism of implementation of managerial decisions to effectively carry out
      priority national projects on health care].
AB  - The paper deals with the special programs implemented within state sanitary-and
      epidemiological surveillance in Moscow as the most important mode for controlling
      a sanitary-and-epidemiological process and the mechanism of a state managerial
      decision-making technology to improve governmental policy in health care and
      sanitary-and-epidemiological well-being. It also shows a role of the state
      sanitary-and-epidemiological service as the main element of governmental policy
      to ensure sanitary-and-epidemiological well-being and prophylaxis of public
      health care.

PMID- 20135861
TI  - [Sanitary-and-epidemiological support of town-planning activities at all stages
      of an investment-construction cycle].
AB  - The paper provides evidence for a need for a systems approach to the sanitary-and
      epidemiological support of construction projects at all stages of an investment
      construction cycle, considers individual stages of work execution, and notes the
      increasing role of laboratory and instrumental studies and measurements at each
      stage. It is emphasized that sanitary-and-epidemiological support (or, in other
      words, sanitary-and-epidemiological audit) of a project (construction products)
      at all stages of an investment-construction cycle is an important and promising
      line in town-planning activities.

PMID- 20135862
TI  - [Radiation safety ensuring in Moscow].
AB  - The paper deals with the structure of Moscow population's radiation safety
      ensuring. By touching upon the problems in ensuring nuclear safety, the author
      points to the fact that there are fundamental differences of nuclear and
      radiation safety. The basic terms used in radiation hygiene are given. The
      structure of the bodies and institutions, which ensure radiation safety, is
      presented; their tasks and duties are briefly outlined. These institutions are
      classified according to their basic function. Main problems in ensuring radiation
      safety are stated.

PMID- 20135863
TI  - [Sanitary and hygienic requirements for location of cars in a megapolis].
AB  - The paper points out that the requirements given in the guidelines to SanPiN
      2.2.1/2.1.1.1200- 03 for locating garages and parking places of different types
      and capacities in Moscow define uniform approaches to solving the problems of
      arranging garage car parks of different types and capacities. The accumulated
      experience in exercising control over the location of garage car parks, by
      applying the requirements laid down in the Guidelines, has been kept in mind when
      developing SanPinN 2.2.1/2.1.1.1200-03 (new wording) approved by the 25
      September, 2007 Resolution No. 74 by the Principal State Sanitary Inspector.

PMID- 20135864
TI  - [Assessment of Moscow population health risk from exposure to ambient air
      suspended matter].
AB  - Ambient air pollution by suspended matter is an environmental factor that has the
      greatest influence on the health status of the majority of the Russian
      Federation's population. There is extensive epidemiological and clinical evidence
      suggesting that ambient air pollution by suspended matter and its fine-dispersed
      fractions PM10 and PM2.5 in particular, poses a serious threat to human health.
      The existing Russian single and average daily maximum permissible concentrations
      of suspended matter are not a high risk from this type of ambient air pollution
      and fail to assess human health damage in full measure. To reduce the
      concentrations of suspended matter and their action on man is currently the
      worldwide priority task whose performance will save much money. There is a need
      to change an air pollution monitoring system (continuous monitoring of fine
      suspended matter of PM10 and PM2.5), as well as to substantiate and introduce
      Russian hygienic standards for fine suspended matter (PM10 and PM2.5).

PMID- 20135865
TI  - [Family health-improving potential as a basis for developing the preventive
      programs].
AB  - The paper provides rationale for the ways of preventing the population's
      diseases, by attracting a family. It presents the results of examining the health
      improving possibilities of a family in the area served by a practitioner (a
      family physician). The results of assessment of the medical activity of a family
      and its performance of medical function and participation in preventive programs
      are given.

PMID- 20135866
TI  - [Manufacturing inspection in ensuring sanitary and epidemiological well-being of
      the population].
AB  - The paper shows the role and place of manufacturing control over the observance
      of the sanitary-and-epidemiological well-being of the population. Necessary
      conditions for the effective functioning of a manufacturing control system are
      formulated.

PMID- 20135867
TI  - [Ways of improving a preventive medical examination system].
AB  - In Moscow, a model of the medical educational center that integrates occupational
      hygienic training and preventive medical examinations of the workers of
      epidemiologically significant projects has been developed and put into practice,
      which permits the complete "one-window" drawing-up of a personal medical record.
      Analysis of the results of practical application of the model of the medical
      educational center based on the existing medical organizations has indicated
      their effectiveness: with the legislatively established reduction in the number
      of check-ups by state sanitary-and-epidemiological surveillance bodies, there is
      an increase in the hygienic education and preventive medical examination coverage
      of the population groups to be examined and there is a functioning mechanism of
      the feedback required to analyze results and to evaluate the efficiency of
      performed medical examinations and hygienic education of the workers.

PMID- 20135868
TI  - [Sanitary and epidemiological opinions for work using ionizing radiation sources
      at the therapeutic and prophylactic institutions].
AB  - The paper deals with the process of obtaining sanitary-and-epidemiological
      reports for a therapeutic-and-preventive institution. Each of the expertise
      stages from the choice of a room to the obtaining a sanitary-and-epidemiological
      opinion and a license is described. Their application and objectives are given.
      The schematic diagram for obtaining a sanitary-and-epidemiological opinion and a
      license is shown. The paper is intended for the specialists of the Russian
      Inspectorate for the Protection of Consumer Rights and Human Welfare and the
      businessmen who are going to deal with operations using ionizing radiation
      sources.

PMID- 20135869
TI  - [Sanitary and hygienic assessment of a scheme for waste disposal and removal at
      outpatient facilities].
AB  - The performed study will allow the practitioners-experts to use a proposed
      procedure for sanitary-and-hygienic expertise of the organization of work to
      accumulate and remove therapeutic-and-prophylactic institution wastes for the
      preparation and issue of an opinion on the document "A4 scheme for waste disposal
      and removal at the institution".

PMID- 20135870
TI  - [Medical and prophylactic nutrition in workers under harmful conditions].
AB  - The paper assesses the traditional and current methods in the organization of
      providing workers with medical and prophylactic products. It raises the question
      as to the value of milk as a detoxicant, an antidote, that aids in eliminating
      harmful substances from the organism of workers who are in contact with noxious
      occupational factors. Consideration of this issue may be presently regarded as
      actually urgent and timely since present-day developments in preventive nutrition
      of the population provide a possibility of using foods (beverages) that are of
      great rational benefit to the health of the persons exposed to poor industrial
      factors.

PMID- 20135871
TI  - [Hygienic requirements for the sizes of furniture for junior pupils].
AB  - The paper gives the results of anthropometric surveys in present-day junior
      pupils. It shows the distribution of junior pupils by the height groups and the
      ergonomic signs that determine the required functional sizes of furniture for
      pupils.

PMID- 20135872
TI  - [Monitoring of the medicodemographic situation in Moscow].
AB  - There has been recently a trend in declining mortality rates in all population
      groups. Higher birth rates and lower mortality have been responsible for a
      reduction in natural population loss in Moscow. At the same time, 14 of the 123
      Moscow municipal districts show a positive natural population growth largely due
      to higher birth rates. Better social and economic living conditions, the
      effective activities of health care bodies and sanitary and epidemiological well
      being services of the city have caused recent positive changes in the demographic
      situation.

PMID- 20135873
TI  - [Experience in toxicological monitoring in Moscow].
AB  - A technology for the toxicological monitoring of chemical poisoning cases in
      Moscow is described. Its results over 2002-2006 are presented. The distribution
      of poisonings by causes, gender, and age, pattern, and occurrence circumstances
      is analyzed. A number of difficulties arising from the filling toxicological
      monitoring record form No. 58-1/y are discussed. The problems facing the
      participants of monitoring are given.

PMID- 20135874
TI  - [Sanitary and hygienic expert examination of consumer goods: toxicological
      aspects].
AB  - The paper presents the results of toxicological and sanitary-chemical studies of
      domestic and imported products subject to sanitary-and-epidemiological
      assessment. It shows the groups of products that are currently the greatest
      potential danger to health in terms of toxicological and hygienic parameters.
      Recommendations are given on programs for manufacturing control over the
      observance of sanitary rules and the antiepidemic (preventive) actions at the
      enterprises engaged in the production and turnover of social consumer goods.

PMID- 20135875
TI  - [Results of epidemiological supervision of malaria vectors in the open water
      reservoirs of Moscow].
AB  - In the past 2 years, the malaria epidemiological situation has drastically
      improved in Moscow: only sporadic cases of local transmission of tertian
      (Plasmodium vivax) malaria have been notified, which sets a task to eradicate
      malaria in the megalopolis in 2010. In this connection, the surveillance of the
      malaria vectors Anopheles mosquitoes is assuming prime importance. The results of
      entomological monitoring have shown its efficiency on the territory of the
      megalopolis. Main efforts have been directed to the application of safe
      controlling methods against the mosquitoes and to hydraulic engineering actions
      to reduce "area susceptibility". Entomological observations have demonstrated
      benefits from the correctly chosen and constantly performed hydraulic engineering
      measures that guarantee a long-term and positive impact on the malaria situation.

PMID- 20135876
TI  - [N. I. Teziakov's contribution to the development of community medicine and
      sanitation in the Saratov Province (on the occasion of the 150th anniversary of
      his birth)].
AB  - The paper provides N. I. Tezyakov's concise biographical and historical data
      pertaining to a sanitary service in the Saratov Province. It shows his scientific
      contribution to the development of community medicine and sanitation in Russia.

PMID- 20135877
TI  - [Relationships between psychosomatics and somatopsychiatry in modern medicine].
AB  - Progress in many clinical disciplines and neurobiology for the last decades give
      reason to reconsider some fundamental provisions of psychosomatic medicine and
      its relationships with somatopsychiatry. The universally accepted biopsychosocial
      model of the disease as proposed by V.N.Bekhterev implies involvement of
      psychological and psychosocial factors at early stages of many forms of somatic
      pathology. Intricate interplay between somatic and psychic components is
      exemplified by correlation of cardiovascular disorders and depression. Depression
      is diagnosed in 17-27% of the patients with coronary heart disease undergoing
      coronary angiography and in 16-45% of the post-infarction cases. Frequency of
      depression/hypertensive disease comorbidity is estimated at 30%. Similarity of
      pathogenetic mechanisms of cardiovascular diseases and depressive states is due
      to stress as their common provoking factor. Another important aspect of the
      relationship between medicine and psychiatry (disregarded until recently) is high
      frequency of somatic disorders in psychiatric patients. Cooperation of
      psychiatrists and representatives of different medical disciplines in such areas
      as research and practical health care is needed to address this problem.

PMID- 20135878
TI  - [Neuroendocrine tumours of pancreas and gastrointestinal tract].
AB  - This paper reviews data on benign and malignant neuroendocrine tumours of
      pancreas and gastrointestinal tract including insulinoma, glucagonoma,
      somatostatinoma, gastrinoma, carcinoid syndrome, and multiple endocrine
      neoplasms. Their origin, prevalence, clinical manifestations, laboratory and
      instrumental diagnosis, surgical and medicamentous treatment are discussed.

PMID- 20135879
TI  - [Pathophysiological and therapeutic aspects of bone lesions in patients with
      multiple myelomas].
AB  - Multiple myeloma (MM) is an uncontrolled malignant proliferation of plasma cells.
      Today, it is the best studied form of hemoblastomas, but many pathophysiological
      and therapeutic aspects of this condition await a deeper insight. The medico
      social significance of the disease is emphasized by its continuous growth,
      variable clinical manifestations, low quality of the patients" life, mean life
      expectancy of 3-5 years, and numerous complications. One clinical feature of MM
      is bone lesions that occur in all patients as osteolysis (OL), osteoporosis (OP),
      hypercalcemia, and combination of these disorders. Progressive degeneration of
      bone tissue even in patients responding to chemotherapy results in severe pain,
      pathological fractures, and neurologic problems. Molecular mechanisms of OL and
      OP in MM have recently attracted much attention. This review summarizes data on
      the role of cytokines, growth factors, osteopontin, OPG-RANK-RANK system,
      macrophage inflammatory proteins, and matrix metalloproteinases in MM-related
      osteodestruction. Iatrogenic origin of bone lesions is considered. Treatment of
      MM using thalidomide (lenlalidomide), proteasome inhibitors (bortesamide), and
      biphosphonates (pamidronate, zoledronic acid) is discussed as the most promising
      therapeutic strategy promoting plasma cell apoptosis, inhibition of bone
      resorption, stabilization of osteoblast function, and pain alleviation.

PMID- 20135880
TI  - [Cytokine and acute phase inflammation reactant levels in men with myocardial
      infarction].
AB  - The role of cytokines, their putative transporters, and other acute phase
      reactants was studied in 17 men aged 57.2 +/- 9.6 yr with microfocal myocardial
      infarction (MI) and in 21 ones with macrofocal MI. Control group comprised 30 age
      matched men. Diagnosis of MI was confirmed by traditional functional tests and
      laboratory methods. It was shown that levels of TNF-alpha and MG-PL transport
      complexes were elevated regardless of MI type whereas acute phase reactants
      increased only in patients with macrofocal MI These patients also had enhanced IL
      6 and IL-8 levels with gradual normalization of the former. In microfocal IM, IL
      8 increased only by day 14. Inhibitory action of TNF-alpha appears to be
      insufficient to suppress effect of macrofocal IM but may be responsible for its
      selective effect on acute phase reactants. The above differences can be used as
      additional criteria for differential diagnosis of micro- and macrofocal MI
      especially in patients with repeated MI or His bundle block when traditional ECG
      data are of poor informative value.

PMID- 20135881
TI  - [Dysfunction of vascular endothelium in patients with coronary heart disease].
AB  - Patients with FC II-IV CHD and angina of effort were divided into 3 groups
      (compensated, subcompensated, and decompensated types) based on vascular reaction
      to local ischemic load Serum lipid spectrum, parameters of hemostasis and blood
      flow were evaluated before and after the load. It was shown that each type of
      vascular reaction had specific predictors. Vasodilation in "compensated" patients
      was largely due to hydrodynamic changes in the vascular bed. The "subcompensated"
      type was characterized by reduced sensitivity to this changes "decompensated"
      type of reactivity was related to metabolic rather than hydrodynamic disorders
      accounting for paradoxic vasoconstriction in response to ischemic load.

PMID- 20135882
TI  - [Holter monitoring for short-term prognostication in patients with myocardium
      infarction].
AB  - Individualized prognosis is a topical problem in the management of acute
      myocardial infarction. Prediction of clinical course and outcome of the disease
      encounters many difficulties since it requires highly sensitive and specific
      measurements that must be safe and technically simple. Prognostic studies related
      to acute myocardial infarction are many, but combined effect of various factors
      remains poorly known. Thus far, clinical conditions of the patients were
      evaluated largely based on medical history data and assays of cardiospecific
      enzymes. The expected outcome of the disease was deduced from the results of
      complicated and expensive studies (e.g. coronaroventriculography) available in
      relatively few medical centres or VEM test usually performed since the 3d week
      after onset of the disease. Most publications do not mention the use of 24 hour
      ECG (Holter) monitoring for immediate prognosis although this method is readily
      available, safe, and can be applied at any stage of the disease. Its sensitivity
      and specificity for the diagnosis of coronary heart disease is 88 and 69%
      respectively. The method can be used to evaluate efficiency of therapy, detect
      arrhythmogenic complications and painless myocardial ischemia in patients with
      myocardial infarction.

PMID- 20135883
TI  - [Free-radical processes in cardiomyopathy and concomitant vibration disease].
AB  - Progression from local vibration to cardiovascular pathology in patients with
      vibration disease is associated with remodeling cardiac and vascular tissues
      under effect of oxidative stress. Myocardium and nodular tissue are most
      vulnerable during development of occupational cardiopathy. Alteration of the
      heart rhythm wave structure is a predictor of remodeling.

PMID- 20135884
TI  - [Specific features of cardiac insufficiency in elderly patients with chronic
      renal disease].
AB  - AIM OF THE STUDY: To evaluate clinical features of chronic cardiac insufficiency
      (CCI) in elderly patients with renal dysfunction. MATERIALS AND METHODS: 260
      patents (143 men and 117 women) aged above 60 (mean 68.7 +/- 6.6) yr with I-IV FC
      CCI. 25 patients had hypertensive disease (HD), 30 coronary heart disease (CHD),
      205 HD+CHD. Glomerular filtration rate (GFR) was estimated using MDRD formula.
      RESULTS: Chronic renal disease (CRD) with GFR reduced below 60 ml/min/1.73 m2 was
      diagnosed in 126 (48.5%) patients. Its severity was not significantly different
      between patients with and without CCI. (2.3 +/- 0.7 and 2.1 +/- 0.7 respectively,
      p = 0.13). The entire study group was dominated by men, the CCI group by women.
      Atrial fibrillation (AF) was diagnosed in 25.8% of the patients with CI + CRD.
      Multivariate regression analysis revealed independent correlation of AF with CCI
      FC (p = 0.02) and GFR (p = 0.2). CCI patients with CRD had higher frequency of
      mitral regurgitation (MR) than without CRD. Occurrence of MR correlated with age
      (p < 0.001) and GFR (p < 0.001). CONCLUSION: 1. Renal dysfunction occurred in
      48.55% of elderly patients with CCI. 2. A distinctive clinical feature of CCI +
      CRD in elderly patients is frequent development of AF and MR. 3. CCI + CRD is
      more frequent in women and CCI without CRD in men.

PMID- 20135885
TI  - [Investigation into relationship between chronic obstructive pulmonary disease,
      bronchial asthma, and type 2 diabetes].
AB  - We studied the relationship between bronchopulmonary pathology (chronic pulmonary
      disease, CPD, and bronchial asthma, BA) and type 2 diabetes (DM2). The two
      conditions were shown to be underlain by inflammation of different character. In
      patients with CPD it leads to DM2. Concomitant CPD and BA significantly increase
      the risk of DM2 and require the development of measures for its diagnosis and
      prevention.

PMID- 20135886
TI  - [Evaluation of psychophysiological status and performance ability in patients
      with hypertensive disease employed under strained working conditions].
AB  - The aim of this work was to study psychophysiological functions in HD subjects
      during strenuous conveyor-belt work. It involved 225 participants of whom 195
      presented with different stages of HD. Group 1 (n = 65) included patients with
      prehypertension, group 2 (n = 69) with stage 1 HD, group 3 (n = 61) with stage II
      HD. Control group comprised 30 healthy subjects. The groups were matched for
      clinical and demographic characteristics. It was shown that performance
      efficiency of the conveyor-belt workers decreased with increasing HD severity.
      Mental functioning was the first to be affected suggesting impairment of
      sensorimotor coordination and attention. Moreover, the performance correlated
      with the patients" age and length of work. The worst results of simple and
      complex visual-motor reaction time tests were obtained in patients above 40 years
      with more than 10 years" conveyor-work experience. Close relation of performance
      efficiency to psychosomatic condition reflects interplay of regulatory mechanisms
      responsible for optimal adaptation of the organism to strenuous work.

PMID- 20135887
TI  - [The use of monopril in elderly patients with arterial hypertension and coronary
      heart disease].
AB  - We examined 20 patients (mean age 69.4 yr) with stage II AH and CHD. 13 ones
      suffered CHD with stable FC II and III angina, two others had myocardial
      infarction. The patients were given monopril, 10 mg BID (08.00 & 20.00). Those
      with CHD were additionally treated with cardiket (20 mg BID) or monocinque (20 mg
      BID). If appropriate, hypothiazide or triampur compositum (25 mg each) was given
      in the morning. Usual clinical examination was supplemented by dynamic studies
      and evaluation of clinical symptoms on day 21 after therapy including systolic
      and diastolic AP, pulse and mean dynamic AD, double product, heart rate, ECG,
      echoCG, AP and ACG monitoring. The above treatment produced marked
      antihypertensive and antianginal effects in the absence of adverse events.

PMID- 20135888
TI  - [Alternative medicine. Past, present, future. Part 2].
AB  - Part 2 highlights the use of food products, bioactive additives, micronutrients,
      and phytotherapyforprevention of diseases. Many studies demonstrated positive
      effect of omega-3 PUFA, stanols, sterols, and esterified pargarines, soluble
      cellulose, controlled alcohol consumption, tea, Mg-enriched dietetic factors,
      folic acid combined with vitamins B6 and B12 on subjects with the initially
      enhanced homocysteine level. Garlic is known to reduce blood lipids, hawthorn may
      be useful at early stages of cardiac insufficiency, ginkgo biloba in arterial and
      cerebral disorders, horse chestnut for the treatment of peripheral vascular
      pathology. Results of controlled studies indicate that the use of many foods for
      prevention of different diseases is currently based on recommendations of
      individual doctors and needs to be substantiated by evidence-based practice.
      Physicians treating and educating patients must be well aware of alternative and
      supplemental therapeutic modalities with the use of foodstuffs, bioactive
      additives, micronutrients, and phytotherapy.

PMID- 20135889
TI  - [Mathematical simulation for the assessment of clinical efficacy of the treatment
      of hypertensive crisis].
AB  - Retrospective analysis included case histories of 182 patients with hypertensive
      disorders and one or more crises (HC). The aim was to study the relationship
      between drug therapy and occurrence of HC. As known, clinical diagnosis of
      hypertensive disorder dictates therapeutic strategy for AH. It was shown that
      diagnosis of neurocirculary dystonia (asthenia) prevented timely prescription
      antihypertensive treatment and resulted in HC. Mathematical simulation of anti-AH
      therapy in the presence of HC allows patients at high risk of stroke to be
      identified for follow-up and adequate treatment.

PMID- 20135890
TI  - [Primary generalized amyloidosis with restrictive cardiomyopathy and severe
      chronic cardiac insufficiency].
AB  - The paper reports a case of restrictive cardiomyopathy due to cardiac
      amyloidosis. Diagnosis of this condition encounters difficulty created by the
      absence of pathognomonic symptoms of the disease. Major manifestations of amyloid
      cardiomyopathy are refractive chronic cardiac insufficiency, absence of
      cardiomyalgia, marked deterioration of diastolic filling of both ventricles,
      systemic hypotension, and disturbed heart rhythms.

PMID- 20135891
TI  - [Late diagnosis of celiac disease].
AB  - A 45 year-old woman presented with late-diagnosed celiac disease, marked
      disorders of calcium and bone metabolism, and severe osteoporosis. Weak enteral
      symptoms delayed diagnosis. High efficiency of agluten and vitamin D therapy was
      documented.

PMID- 20135892
TI  - [Cardiac syndrome X: peculiarities of pathogenesis, clinical course, and
      treatment].

PMID- 20135893
TI  - [Twelve co-morbidity theses].

PMID- 20135894
TI  - The intersection of pharmacology, imaging, and genetics in the development of
      personalized medicine.
AB  - We currently rely on large randomized controlled trials and meta-analyses to make
      clinical decisions; this places us at a risk of discarding subgroup or
      individually specific treatment options owing to their failure to prove
      efficacious across entire populations. There is a new era emerging in
      personalized medicine that will focus on individual differences that are not
      evident phenomenologically. Much research is directed towards identifying genes,
      endophenotypes, and biomarkers of disease that will facilitate diagnosis and
      predict treatment outcome. We are at the threshold of being able to predict
      treatment response, primarily through genetics and neuroimaging. In this review
      we discuss the most promising markers of treatment response and adverse effects
      emerging from the areas of pharmacogenetics and neuroimaging in depression and
      schizophrenia.

PMID- 20135895
TI  - Policy perspectives on the emerging pathways of personalized medicine.
AB  - Remarkable advances in the fundamental knowledge about the biological basis of
      disease and technical advances in methods to assess genomic information have led
      the health care system to the threshold of personalized medicine. It is now
      feasible to consider strategic application of genomic information to guide
      patient management by being predictive, preemptive, and preventive, and enabling
      patient participation in medical decisions. Early evidence of this transition has
      some hallmarks of disruptive innovation to existing health care practices.
      Presented here is an examination of the changes underway to enable this new
      concept in health care in the United States, to improve precision and quality of
      care through innovations aimed at individualized approaches to medical decision
      making. A broad range of public policy positions will need to be considered for
      the health care delivery enterprise to accommodate the promise of this new
      science and technology for the benefit of patients.

PMID- 20135896
TI  - The role of neuroimaging in diagnosis and personalized medicine--current position
      and likely future directions.
AB  - The main aim of this article is to discuss the current state of in vivo brain
      imaging methods in the context of the diagnosis and treatment of mental illness.
      The background to current practice is discussed, and the new methods introduced
      which may have the capacity to increase the relevance of magnetic resonance
      imaging, particularly functional magnetic resonance imaging, for clinical
      application. The main focus will be on magnetic resonance imaging, but many of
      the comments have a general relevance across imaging modalities.

PMID- 20135897
TI  - Stem cell approaches in psychiatry--challenges and opportunities.
AB  - Exploring stem cells is a fascinating task, especially in a discipline where the
      use of stem cells seems far-fetched at first glance, as is the case in
      psychiatry. In this article we would like to provide a brief overview of the
      current situation in relation to the treatment of mental diseases. For reasons
      that we will explain, this review will focus on affective disorders. The
      following section will give a more detailed account of stem-cell biology
      including current basic science approaches presenting in-vivo and in-vitro
      techniques. The final part will then look into future perspectives of using these
      stem cells to cure mental illnesses, and discuss the related challenges and
      opportunities.

PMID- 20135898
TI  - Pharmacogenetics of antipsychotic-induced side effects.
AB  - Currently available antipsychotic drugs (APDs) carry significant though highly
      variable, liability to neurologic and metabolic side effects. Pharmacogenetics
      approaches offer the possibility of identifying patient-specific biomarkers for
      predicting risk of these side effects. To date, a few single nucleotide
      polymorphisms (SNPs) in a handful of genes have received convergent support
      across multiple studies. The primary focus has been on SNPs in dopamine and
      serotonin receptor genes: persuasive meta-analytic evidence exists for an effect
      of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardive
      dyskinesia (TD) and for an effect of variation at the 5-HT2C receptor gene
      (HTR2C) for liability to APD-induced weight gain. However, effect sizes appear to
      be modest, and pharmacoeconomic considerations have not been sufficiently
      studied, thereby limiting clinical applicability at this time. Effects of these
      genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia,
      and weight gain are reviewed in this article.

PMID- 20135900
TI  - Personalized medicine in psychiatry: ethical challenges and opportunities.
AB  - Pharmacogenomic developments hold promise for personalized medicine in psychiatry
      with adjusted therapeutic doses, predictable responses, reduced adverse drug
      reactions, early diagnosis, and personal health planning. The prospects are
      exciting, but at the same time, these new techniques stand faced with important
      scientific, ethical, legal, and social challenges that need to be met in order
      for the scientific advances to be responsibly applied. This review discusses the
      ethical balance between challenge and opportunity of personalized medicine in
      psychiatry under the aspects of adequacy, cost:benefit ratio, and therapeutic
      equity. It is argued that the promising nature of these therapeutic possibilities
      makes it all the more important to avoid exaggerating the expectations, and that
      a sophisticated social infrastructure needs to be developed in order to ensure
      the realistic and responsible application of personalized medicine in psychiatry.

PMID- 20135899
TI  - Major depression during interferon-alpha treatment: vulnerability and prevention.
AB  - Major Depressive Disorder (MDD) during interferon-alpha (IFN-alpha) treatment can
      occur within a few months of therapy, and shares many homologies with other forms
      of MDD. Most patients are resilient to the side effect of interferon-induced
      depression (IFN-MDD), but 15% to 40% are vulnerable. Several studies have
      employed antidepressants to prevent the incidence of an IFN-MDD episode, and the
      results suggest that prophylactic antidepressants may be specifically useful in
      those with pre-existing subthreshold depressive symptoms and/or a history of
      prior MDD episodes. Several other potential markers of vulnerability for IFN-MDD
      have been implicated in assessments of nondepressed patients before they start
      IFN-alpha. These include poor sleep quality, premorbid elevations in inflammatory
      cytokines, genetic polymorphisms in the serotonin system, personality, and social
      support. The interplay of these factors strongly predicts who is at risk for IFN
      MDD, and indicates several potentially modifiable targets for the personalized
      prevention of IFN-MDD.

PMID- 20135901
TI  - A new paradigm for the prediction of antidepressant treatment response.
AB  - Current treatment of Major Depressive Disorder utilizes a trial-and-error
      sequential treatment strategy that results in delays in achieving response and
      remission for a majority of patients. Protracted ineffective treatment prolongs
      patient suffering and increases health care costs. In addition, long and
      unsuccessful antidepressant trials may diminish patient expectations, reinforce
      negative cognitions, and condition patients not to respond during subsequent
      antidepressant trials, thus contributing to further treatment resistance. For
      these reasons, it is critical to identify reliable predictors of antidepressant
      treatment response that can be used to shorten or eliminate lengthy and
      ineffective trials. Research on possible endophenotypic as well as genomic
      predictors has not yet yielded reliable predictors. The most reliable predictors
      identified thus far are symptomatic and physiologic characteristics of patients
      that emerge early in the course of treatment. We propose here the term "response
      endophenotypes" (REs) to describe this class of predictors, defined as latent
      measurable symptomatic or neurobiologic responses of individual patients that
      emerge early in the course of treatment, and which carry strong predictive power
      for individual patient outcomes. Use of REs constitutes a new paradigm in which
      medication treatment trials that are likely to be ineffective could be stopped
      within 1 to 2 weeks and other medication more likely to be effective could be
      started. Data presented here suggest that early changes in symptoms, quantitative
      electroencephalography, and gene expression could be used to construct effective
      REs. We posit that this new paradigm could lead to earlier recovery from
      depressive illness and ultimately produce profound health and economic benefits.

PMID- 20135902
TI  - Prevention: an achievable goal in personalized medicine.
AB  - In the past 15 years a considerable number of studies have found evidence that it
      may be possible to prevent the onset of some mental disorders. Most evidence is
      available for depressive disorders, but a growing number of studies have focused
      on anxiety disorders and psychotic disorders. This paper reviews the studies
      which have examined the effects of preventive interventions on the incidence of
      mental disorders in people who do not meet criteria for a mental disorder at
      baseline. More than 20 studies have examined prevention of depressive disorders,
      and they have found an overall reduction in the incidence of about 25% compared
      with control groups. The problem of identifying the most optimal target groups
      for preventive interventions is also illustrated. This is a problem because most
      risk indicators have a low specificity, and most people with a risk indicator do
      not develop a mental disorder. Finally, this paper will show how other
      statistics, such as the exposure rate, the attributable fraction, and the number
      needed to treat can help in identifying the most optimal target groups for
      preventive interventions.

PMID- 20135903
TI  - Shared decision making in mental health: prospects for personalized medicine.
AB  - This paper describes the shared decision-making model, reviews its current status
      in the mental health field, and discusses its potential impact on personalized
      medicine. Shared decision making denotes a structured process that encourages
      full participation by patient and provider. Current research shows that shared
      decision making can improve the participation of mental health patients and the
      quality of decisions in terms of knowledge and values. The impact of shared
      decision making on adherence, illness self-management, and health outcomes
      remains to be studied. Implementing shared decision making broadly will require
      re-engineering the flow of clinical care in routine practice settings and much
      greater use of information technology. Similar changes will be needed to combine
      genomic and other biological data with patients' values and preferences and with
      clinicians' expertise. The future of personalized medicine is clearly linked with
      our ability to create the infrastructure and cultural receptivity to these
      changes.

PMID- 20135904
TI  - Personalized medicine: selected web resources.
AB  - Information about personalized medicine abounds, yet it is difficult to
      comprehensively search for information on this topic due to the broadness of the
      term "personalized medicine," the variety of terms that are used to describe this
      concept, the vast amount of pertinent journal articles and Web sites, and the
      fast pace of developments in this field. A selected list of Web sites is provided
      as a starting place for information about concepts, terminology, projects,
      databases, tools, and stakeholders related to personalized medicine.

PMID- 20135905
TI  - Foetal stress responses to euthanasia of pregnant sheep.
AB  - The study was designed to evaluate foetal stress responses in midgestational (G1)
      and near-term (G2) pregnant ewes euthanized either by intravenous administration
      of pentobarbital (group P) or electrical current (group E). After the ewe's death
      foetal lambs were delivered by caesarean section and remained attached to the ewe
      by the umbilical cord. Foetal vitality, reflexes, heart rate, blood pressure,
      rectal body temperature, venous pCO2, pH and lactic acid were monitored.
      Additionally, foetal plasma concentrations of pentobarbital were determined in
      group P. Neither electrocution of the pregnant ewe nor euthanasia of the dam by
      pentobarbital caused cardiac arrest in foetuses within 25 minutes. G1-foetuses of
      group P lost significantly faster all body movements and reflexes whereas G2
      foetuses of group P took significantly longer in reaching a venous pH < 7.0 and a
      pCO2 > 13.33 kPa as well as a blood lactate concentration of > 8 mmol/l. Since no
      scientific evidence has been found yet to what extent the foetal lamb can
      experience pain and can suffer, the prolonged process of dying for group-E
      foetuses due to hypoxia is inconsistent with criteria for humane euthanasia and
      animal welfare. The administration of pentobarbital to the pregnant ewe, however,
      might have the potential to induce foetal anaesthesia thereby satisfying the main
      aspects of the definition of humane euthanasia to a greater extent.

PMID- 20135906
TI  - [Effects of weaning age on behavioural and physiological responses of domestic
      piglets--a review].
AB  - Weaning of farm animals is of biological and economical relevance. Due to
      economical considerations, the weaning age of piglets (Sus scrofa) has
      drastically been reduced during the last few years, whereas biological
      consequences remain ambiguous. This review gives a survey of current
      international research on weaning and its psychobiological consequences in
      conventional pig farming. The influence of weaning age on behaviour,
      neuroendocrine and immune systems of piglets is the main focus of this paper. The
      abrupt weaning in pig farming comprises multiple stressful events such as change
      in diet, new physical environment, as well as the often underestimated
      psychosocial consequences of maternal deprivation and regrouping with unfamiliar
      conspecifics. Results presented in this review suggest that early weaned piglets
      (< or = 21 days of age) show enhanced behavioural problems and neuroendocrine
      stress reactions as well as reduced immune responses. These adaptation problems
      may have short- and long-term effects on animals' welfare and health,
      consequently resulting in increased financial requirements and higher management
      demands. Weaning before the third week of age is not recommended. Additionally,
      alternative housing systems (e.g. group housing) with adequate weaning methods
      (e.g. weaning without regrouping, social contacts prior to weaning) to diminish
      psychosocial stress are discussed.

PMID- 20135907
TI  - Molecular classification and its impact on diagnostics and understanding the
      phylogeny and epidemiology of selected members of Pasteurellaceae of veterinary
      importance.
AB  - In this paper we briefly report recent taxonomic changes that have taken place
      within the bacterial family Pasteurellaceae as a result of molecular
      investigations. We address the complexity and diagnostic possibilities and
      outline the current knowledge on the population structure these investigations
      have generated. In addition, we discuss future possibilities to improve basic
      understanding of genetic diversity at population level, possible host adaptation
      and stability of clones associated with disease outbreaks. All taxa of
      Pasteurellaceae have been characterized by 16S rRNA gene sequencing, and the 16S
      rRNA gene sequence has been the starting point for classification and
      identification of most taxa, including PCR detection methods developed.
      Generally, it is preferred to isolate and store the bacterium before
      characterization is carried out, however, if this is impossible, a PCR test can
      be carried out on DNA extracted from suspected material. Fluorescent in situ
      hybridization (FISH) is a possibility for only a few members of Pasteurellaceae.
      Identification based on the partial rpoB sequence is possible when a high
      simililarity to a sequence of a well known reference strain is found. Multilocus
      sequence typing (MLST) is only available for a few taxa of Pasteurellaceae of
      veterinary importance including [Haemophilus] parosuis, Mannheimia haemolytica,
      Pasteurella multocida and Actinobacillus pleuropneumoniae. Application of this
      method for characterization of broad strain collections has improved our
      knowledge on population level significantly, and added to our understanding of
      disease manifestations. Current improvements in progress focus on sequence based
      identification at the population level reflecting that disease and persistence,
      host associations and host response are expressed at the clonal population level
      rather than at the species level.

PMID- 20135908
TI  - Bone marrow depletion with haemorrhagic diathesis in calves in Germany:
      characterization of the disease and preliminary investigations on its aetiology.
AB  - Since 2007 a new fatal haemorrhagic diathesis in calves has been observed in all
      areas of Germany. Analysis of 56 cases submitted for necropsy allowed its
      characterization. Calves fell ill within the first month of life independent of
      breed and sex. Only single or a few animals per herd were affected. Petechial and
      ecchymotic haemorrhages in many organs and tissues, particularly in skin,
      subcutis and gastrointestinal tract, were major findings in all animals.
      Microscopically a severe depletion of bone marrow cells was always observed.
      Lymphocytic depletion (43%) and inflammatory lesions (46%) were less frequently
      observed. Blood analysis of five animals indicated an aplastic pancytopenia. The
      resulting thrombocytopenia is regarded as major pathomechanism of this
      Haemorrhagic Disease Syndrome (HDS). Pedigree analysis gave no indication of
      hereditary disease. Tests for specific toxins such as S-(1,2-Dichlorovinyl)-L
      cysteine (DCVC), furazolidone, or mycotoxins resulting in bone marrow depletion
      were negative. Bacterial infections, Bovine Viral Diarrhoea Virus, and Bluetongue
      Virus were ruled out as cause of the disease. HDS shares similarities with a
      circoviral infection in chickens (chicken infectious anaemia). A broad-spectrum
      PCR allowed detection of circoviral DNA in 5 of 25 HDS cases and in 1 of 8 non
      HDS cases submitted for necropsy. Sequencing of the whole viral genome revealed a
      high similarity (up to 99%) with Porcine Circovirus type 2b. Single bone marrow
      cells stained weakly positive for PCV2 antigen by immunohistochemistry in 1 of 8
      tested HDS animals. This is the first report of circovirus detection in cattle in
      Germany. The exact cause of HDS still remains unknown. A multifactorial aetiology
      involving infection, poisoning, immunopathy, or a genetic predisposition is
      conceivable. Additional research is necessary to clarify the pathogenesis and the
      potential role of PCV2 in HDS.

PMID- 20135909
TI  - Prevalence of feline haemoplasma infection in cats in Southern Bavaria, Germany,
      and infection risk factor analysis.
AB  - In this prospective study performed from samples of 296 cats from Southern
      Bavaria, Germany, a conventional PCR (polymerase chain reaction) assay for
      detection of Mycoplasma haemofelis and "Candidatus Mycoplasma haemominutum" and a
      real-time PCR for "Candidatus Mycoplasma turicensis" were used to test blood
      samples from ill cats with anaemia (n = 79), ill cats with a normal haematocrit
      (n = 98), and healthy cats (n = 119). The aim of the study was to investigate the
      prevalence of feline haemoplasma infection and associated risk factors in cats in
      Southern Bavaria, Germany. Thirty-six cats (12.2%) were PCR positive: 9.5% were
      infected with "Candidatus M. haemominutum, 1.4% with M. haemofelis, and 0.3% with
      "Candidatus M. turicensis". Three cats (1.0%) were coinfected with two
      haemoplasma species (one cat with "Candidatus M. haemominutum"and M. haemofelis,
      and two cats with "Candidatus M. haemominutum"and "Candidatus M. turicensis").
      Risk factors for infection were outdoor access, male gender, coinfection with
      feline leukaemia virus (FeLV), and domestic shorthair breed. There was no
      significant difference in the prevalence of haemoplasma infection between the
      three groups and none of the positive cats had clinical signs of haemoplasma
      infection. The authors conclude that feline haemoplasma infection does not appear
      to be a common cause of anaemia in cats in Southern Bavaria, Germany.

PMID- 20135910
TI  - Ovine coccidiosis in housed lambs in Saxony-Anhalt (central Germany).
AB  - The course of coccidiosis in lambs and the species of Eimeria involved were
      investigated in Saxony-Anhalt, Germany. A field study was conducted on three
      farms (conventional lamb-fattening farms) with 59 lambs. A total of 1092 faecal
      samples were taken during a period from about two to seven weeks after birth; the
      Eimeria species involved were determined in 415 of these samples and
      morphometrical characteristics of oocysts of 12 Eimeria spp. were recorded.
      Subclinical to moderate clinical coccidiosis was observed on all the farms and
      infections with Eimeria spp. were detected in all study lambs. 12 Eimeria species
      were identified on two of the farms (A and C): E. ahsata, E. bakuensis, E.
      crandallis, E. faurei, E. granulosa, E. intricata, E. marsica, E. ovinoidalis, E.
      pallida, E. parva, E. punctata and E. weybridgensis. The majority of these
      species were also detected on farm B, with the exception of E. granulosa, E.
      intricata and E. punctata. To our knowledge this is the first reported occurrence
      of E. punctata in Germany. Specimens with 3, 4 and 5 Eimeria spp. were the most
      common. E. ovinoidalis predominated in the faecal samples which underwent oocyst
      differentiation (> 90% positive samples on each farm). This species also
      accounted for the generally high oocyst counts observed. Since even subclinical
      coccidiosis may entail economic losses in lamb-rearing and considering the high
      prevalence of the pathogenic species E. ovinoidalis, appropriate monitoring of
      the disease in these farms is advisable.

PMID- 20135911
TI  - Presence of Listeria, Arcobacter, and Campylobacter spp. in dairy farms in Spain.
AB  - Bacteria from genera Listeria, Campylobacter and Arcobacter are potentially
      zoonotic pathogens for humans and they may be detected in dairy cattle farms. In
      this study the presence of these bacteria was considered in dairy cattle farms in
      Galicia (northwest of Spain). In the first part of the study, bulk tank milk
      samples were collected to determine the herd prevalences of Listeria spp. in 98
      dairy farms. Additionally 83 silage samples and 97 faeces samples of lactating
      cows were collected. L. monocytogenes was detected in 6.1%, 9.3% and 6.0% of
      these samples, respectively. With regard to Campylobacter spp. and Arcobacter
      spp., 254 faecal samples were collected on 89 dairy farms. Campylobacter spp. was
      found with a herd prevalence of 36%. It was also confirmed in 20.5% of dairy
      cattle faecal samples. Arcobacter spp. was isolated in 68.5% of the farms and in
      41.7% of faecal samples, with A. cryaerophilus being the most frequently
      identified species. The results related to the prevalence of the bacteria
      included in this study confirm their presence in high numbers in different types
      of biological samples from dairy farms, and suggest that more epidemiological
      studies regarding this bacteria need to be performed.

PMID- 20135912
TI  - Alveolar echinococcosis in a captive red-necked wallaby (Macropus rufogriseus).
AB  - A 2.5-year old male red-necked wallaby (Macropodus rufogriseus) kept privately in
      an outdoor enclosure in Germany died with severe jaundice and abdominal
      enlargement. Post mortem examination revealed ascites, and multiple nodular
      lesions in liver, diaphragm, omentum, mesentery, spleen, lung, hepatic and
      thoracic lymph nodes. Histologically, the nodules consisted of predominantly
      fertile larval tissue of a taeniid cestode, necrosis and granulomatous
      inflammation. Echinococcus multilocularis infection was confirmed by PCR.
      Macropodids have therefore to be added to the list of intermediate hosts which
      can develop alveolar echinococcosis.

PMID- 20135913
TI  - [Multiple myeloma in a Yucatan Pig].
AB  - An 11 years old Yucatan Pig with a Multiple Myeloma in the spinal cord, the
      sternum and the pelvis is described. The major clinical sign was a paresis of the
      hind limb. The most significant haematological change was a lymphopenia. The X
      ray examination and computed tomography showed typical osteolytic changes in the
      skeleton. The histological examination of the bone marrow showed many, moderately
      well-differentiated plasma cells. Based on the collected findings and the
      exclusion of differential diagnoses, a Multiple Myeloma was diagnosed.

PMID- 20135914
TI  - [Influence of physiological disturbances on treatment success of dietary therapy
      in dogs with chronic enteropathies].
AB  - The aim of this retrospective study in 40 dogs with chronic inflammatory
      enteropathies was to investigate a possible influence of immunologic and
      metabolic deficiencies on the success of dietary treatments. At the time of
      initial presentation, routine clinical and laboratory methods were used to
      evaluate various metabolic (i.e., weight loss, measurement of serum total
      protein, albumin, and cobalamin concentrations) and immunological parameters
      (i.e., serum globulin concentration, immunoglobulin-fractionation by serum
      electrophoresis, and serum C-reactive protein concentration as measured by a
      species-specific ELISA). The dogs were classified as food-responsive (FR-group, n
      = 11), antibiotic-responsive (AR-group, n = 12), steroid-responsive (SR-group, n
      = 11), or dogs with various combinations of therapies due to protein-losing
      enteropathy (PLE-group, n = 6). Differences among the four treatment groups were
      evaluated by statistical analysis. Compared to dogs in the AR, SR, and PLE
      groups, dogs in the FR-group showed a significantly milder weight loss (p < 0.01
      for each). Dogs in the FR-group also had significantly higher serum
      concentrations of total protein and albumin compared to the PLE-group (p < 0.001
      for each). The FR-group had significantly higher median concentrations of total
      globulin and gamma-globulin fractions compared to the AR- and PLE-groups (p
      <0.005 and p < 0.01, respectively). Lower gamma-globulin concentrations
      correlated with increased weight loss (Spearman r = -0.53; p < 0.005), serum
      cobalamin (Spearman r = 0.38; p < 0.05), and albumin (Spearman r = 0.45; p <
      0.01). Increased serum concentrations of C-reactive protein correlated inversely
      with serum concentrations of cobalamin (Spearman r = -0.58; p < 0.05) and gamma
      globulins (Spearman r = -0.6; p < 0.005). This study provides evidence for a
      possible association between the severity of immunological disturbances and the
      development of deficiencies in dogs with chronic enteropathies. This study
      provides further evidence that less severe physiological disturbances, such as
      milder forms of weight loss and higher serum concentrations of albumin, globulin,
      and gamma-globulin are possibly associated with a more favorably response to
      dietary treatment alone.

PMID- 20135915
TI  - [Effects of different dilution levels on bull- and ejaculate related variability
      of plasmamembran integrity, acrosomal damage and DNA-integrity of cryopreserved
      bull spermatozoa].
AB  - In this study the effects of three different dilution levels (60, 30 and 15
      Mio/ml) on quality of cryopreserved bovine sperm were investigated. Particularly
      it was tested, if effects of dilution in regard to sperm quality were related to
      the factors bull or ejaculate. The following parameters were analysed in four
      ejaculates each of 42 bulls: percentage of plasma membrane intact sperm (PMI),
      percentage of sperm with acrosomal damage (AS) as well as percentage of sperm
      with a high DNA-fragmentation index (DFI%) following cryopreservation. PMI-values
      decreased (p < 0.05) with increasing degree of dilution. AS-values were not
      influenced (p > 0.05) by dilution level. There was a decline in DFI% (p <0.05)
      with increasing dilution of the ejaculate. Coefficient of variation for PMI, AS
      and DFI% were not (p > 0.05) influenced by dilution. The effects of the factor
      ejaculate on the variabilities of PMI and AS were higher than the effects of the
      factor bull. Variability of DFI% depended at the highest dilution level more on
      the factor bull and in the lowest dilution level more on the factor ejaculate. In
      conclusion, these results show that dilution of sperm has positive as well as
      negative effects on sperm quality. With increasing dilution the effect of the
      factor bull on plasma membrane- and acrosomal integrity.

PMID- 20135916
TI  - Advocacy: essential to the growth of the PA profession.

PMID- 20135917
TI  - A call for physician assistants to make a ruckus--and a difference.

PMID- 20135918
TI  - New drug information: Twynsta 40 mg/5mg.

PMID- 20135919
TI  - What is the best way to manage this severe rash?

PMID- 20135920
TI  - MCI and dementia: diagnosis and treatment.

PMID- 20135921
TI  - Elder care: immunization schedules and screening after age 65 years.

PMID- 20135922
TI  - Portal vein encasement complicates resection of Klatskin's tumor.

PMID- 20135923
TI  - Acceptance of physician assistants and nurse practitioners in trauma centers.
AB  - OBJECTIVE: Census data published by professional organizations indicate an upward
      trend in the number of physician assistants (PAs) working in many specialty
      fields, including the subspecialty of trauma surgery. As the role of hospital
      based PAs and nurse practitioners (NPs) continues to evolve, greater
      understanding of these roles will help identify future employment trends for
      these professions. The purpose of this study is to determine the prevalence of
      PAs and NPs in US trauma centers, to document their roles, and to identify their
      potential future utilization by trauma centers. METHODS: A survey was mailed to
      464 directors of major trauma centers in the United States. The survey was
      designed to evaluate trauma centers' utilization of PAs/NPs. Respondents were
      asked to identify specific daily tasks of PAs/NPs and to indicate potential for
      their future utilization. RESULTS: Two hundred forty-six (246) of 464 surveys
      were returned, for a response rate of 53%. Approximately one-third of reporting
      major trauma centers reported utilizing PAs/NPs. More American College of
      Surgeons (ACS)-verified trauma facilities utilized PAs/NPs than did nonverified
      facilities; and Level I trauma centers used significantly more PAs/NPs than did
      Level II trauma centers. Nineteen percent (19%) of respondents who did not
      currently utilize PAs/NPs indicated that they intended to do so in the future.
      The majority of facilities utilized PAs/NPs to assist with trauma resuscitation
      and in performing traditional tasks, including obtaining and dictating histories
      and physical findings, participating in rounds on the general medical floor, and
      dictating discharge summaries. Fewer than half of reporting facilities indicated
      that PAs/NPs performed more invasive procedures, such as inserting arterial
      lines, central lines, chest tubes, and intracranial pressure monitors.
      CONCLUSIONS: PAs and NPs are increasingly utilized as clinicians in the surgical
      subspecialty of trauma. In most trauma centers, PAs/NPs are utilized to complete
      the traditional duties of a surgical PA/NP, with fewer performing invasive
      procedures. Finally, 19% of responding trauma centers who do not currently
      utilize PAs/NPs state that they intend to in the future, indicating the potential
      for continued job growth for PAs/NPs in trauma care. This evaluation of the
      utilization of PAs/NPs in direct care to trauma patients indicates acceptance of
      PAs/NPs in trauma staffing models.

PMID- 20135924
TI  - Safety and adherence: issues that hinder childhood vaccinations.

PMID- 20135925
TI  - The role of genetics in understanding racial and ethnic health disparities.

PMID- 20135926
TI  - What is a heart catheterization?

PMID- 20135927
TI  - Classic adolescent injury mimics a twisted ankle.

PMID- 20135928
TI  - Giant cell arteritis; chronic renal disease.

PMID- 20135929
TI  - Case of the month. Acute sigmoid diverticulitis.

PMID- 20135930
TI  - Biologic mesh for abdominal wall reconstruction: a critical appraisal.

PMID- 20135931
TI  - The general surgery residency at Orlando Health: past, present, and future.

PMID- 20135932
TI  - Lack of complications in skin surgery of patients receiving clopidogrel as
      compared with patients taking aspirin, warfarin, and controls.
AB  - Clopidogrel, a new antiplatelet agent that irreversibly inhibits platelet
      aggregation, is widely used today. This prospective work was conducted to
      evaluate the safety of performing skin surgery on patients taking clopidogrel.
      Patients undergoing surgery for excision of skin or subcutaneous lesions under
      local anesthesia taking clopidogrel were the study group. The control group
      comprised 2073 historical patients who had undergone a similar procedure. Data
      collected included: age, sex, past medical history, medications, and late
      complications. Follow-up was done at 1 to 2 weeks and 3 to 6 months. There were
      32 patients on clopidogrel, having 38 lesions removed. Of these, seven patients
      were on aspirin and clopidogrel combined. The groups taking clopidogrel, aspirin,
      and warfarin had significantly more males, were older, and had significantly more
      comorbid medical conditions. There was no significant difference in the incidence
      of any of the complications in any of the groups. This study shows that patients
      taking clopidogrel before skin surgery, though older and with more associated
      medical conditions, do not experience a greater rate of complications. We
      conclude that patients undergoing minor excisional cutaneous surgery should
      continue taking clopidogrel because there is no apparent risk for increased
      complications when good meticulous surgical techniques are used.

PMID- 20135933
TI  - Novel bacterial immobilization compound effectively decreases bacterial counts in
      healthy volunteers.
AB  - Skin flora immobilization technology is similar in efficacy to Iodine-Povidone in
      healthy volunteers. We did a prospective study in a university clinic with 60
      healthy volunteers. Right inguinal skin area on healthy volunteers was used to
      compare the antimicrobial properties of cyanoacrylate sealant (FloraSeal,
      Adhesion Biomedical, Wyomissing, PA) versus standard surgical preparation
      Povidone-iodine (Betadine, Purdue Productions, Stamford, CT). Bacterial counts
      were measured at different time intervals: 15 minutes, 4 hours, and 24 hours.
      Bacterial colony forming units were compared between Povidone-iodine and
      cyanoacrylate sealant. The absolute log reduction was 5.568 for Povidone-iodine
      (7 absolute CFU); 5.028 for cyanoacrylate (59 absolute CFU); and 5.568 for
      Povidone-iodine and cyanoacrylate combined (21 absolute CFU). Cyanoacrylate was
      able to sustain a reduction on bacterial counts at 4 hours and 24 hours of more
      than 99.8 per cent as compared with the control group. Cyanoacrylate microbial
      sealant successfully reduces bacterial counts on normal healthy skin. The results
      were similar to Povidone-iodine alone. We believe this technology may be an
      excellent means of mitigating incisional surgical site infection by reducing the
      risk of contamination by skin flora and warrants further testing.

PMID- 20135934
TI  - Extreme blood alcohol level is associated with increased resource use in trauma
      patients.
AB  - This study aims to examine resource utilization and outcomes of trauma patients
      with extremely high blood alcohol concentrations. We hypothesized that higher
      blood alcohol concentration (BAC) predicts greater resource utilization and
      poorer outcomes. A retrospective analysis was performed on trauma patients
      admitted to an urban Level I trauma center over a 5-year period. Admission BAC
      categories were constructed using standard laboratory norms and legal
      definitions. Demographic data, premorbid conditions, injury severity scores
      (ISS), resource utilization (intensive care unit (ICU) admission rates/length of
      stay, total hospital days, use of consultants), and mortality were analyzed.
      Positive BAC on admission was associated with increased ISS (P < 0.001), length
      of stay (P < 0.003), and total ICU days (P < 0.001). Increased BAC admission
      level of patients was associated with a decreased ISS score (P = 0.0073), a
      higher probability of ICU admission (P = 0.0013), and an increased percentage of
      ICU days (P = 0.001). A positive BAC at admission was a significant predictor of
      both ICU admission and mortality (odds ratios 1.72 and 1.27, respectively). This
      study demonstrates that a positive BAC is associated with increased ISS,
      increased resource utilization, and worsened outcomes. Extreme levels of BAC are
      associated with increased resource utilization despite lower injury severity
      scores.

PMID- 20135935
TI  - A band lifting assisted method for laparoscopic resection of gastrointestinal
      stromal tumors on the posterior wall of the stomach.
AB  - Laparoscopic surgical techniques are beneficial for the wedge resection of
      gastrointestinal stromal tumors (GISTs). We have developed a new technique of
      laparoscopic transgastric resection for GISTs of the posterior wall of the
      stomach, a band lifting wedge resection method that has been confirmed to ensure
      sufficient surgical margins around the resected specimen in 21 cases. GISTs
      located at the posterior wall of the stomach were collected for this study.
      Laparoscopic anterior gastrotomy was performed and a 9-Fr rubber band was looped
      around the base of the tumor, allowing it to be lifted up through the anterior
      gastrotomy. The lesion was transected using a laparoscopic linear cutter and the
      gastrotomy was then closed by sequential application of the linear cutter.
      Surgical specimens were examined immunohistochemically. All GISTs were
      successfully and completely resected using the laparoscopic technique. The
      resected tumors were ellipse-shaped or round. Macroscopic examination of the
      resected specimens showed complete tumor excision with negative surgical margins
      in all patients. A band lifting method for transection of GISTs on the posterior
      wall of the stomach easily allows for sufficient surgical margins of GISTs. The
      technique is reliable and feasible for laparoscopic treatment of GISTs in the
      stomach.

PMID- 20135936
TI  - An evaluation of lymph node yield and lymph node ratio in well-differentiated
      thyroid carcinoma.
AB  - It is unknown whether the number of lymph nodes harvested (lymph node yield, LNY)
      or the proportion of metastatic lymph nodes resected (metastatic lymph node
      ratio, MLNR) influence survival in well-differentiated thyroid carcinoma (WDTC).
      We hypothesized that overall survival in WDTC is influenced by the LNY and MLNR.
      We used the Surveillance, Epidemiology, and End Results database to identify all
      patients with primary, nonmetastatic WDTC who underwent thyroidectomy with at
      least one lymph node removed between 1988 and 2004. Kaplan-Meier survival curves
      for LNY and MLNR were compared using the log rank test. Multivariate Cox
      proportional hazards models included tumor and patient-specific factors. WDTC
      patients that met entry criteria totaled 9926. In the univariate model, LNY and
      MLNR had a significant impact on survival (P < 0.001). In multivariate analysis,
      increasing LNY was associated with poorer survival in all patients (P = 0.001)
      and node-negative patients (P = 0.03), but not for node-positive patients (P =
      0.27). MLNR did not influence survival in node-positive patients (P = 0.84).
      Among patients with WDTC treated with thyroidectomy and lymphadenectomy,
      increasing LNY and MLNR were associated with decreased survival. The decrease in
      survival associated with increasing LNY, even in node-negative patients,
      indicates that nodal understaging is inconsequential to WDTC survival.

PMID- 20135937
TI  - Surgical anatomy of the retroperitoneal spaces part II: the architecture of the
      retroperitoneal space.
AB  - The extraperitoneal space extends between peritoneum and investing fascia of
      muscles of anterior, lateral and posterior abdominal and pelvic walls, and
      circumferentially surrounds the abdominal cavity. The retroperitoneum, which is
      confined to the posterior and lateral abdominal and pelvic wall, may be divided
      into three surgicoanatomic zones: centromedial, lateral (right and left), and
      pelvic. The preperitoneal space is confined to the anterior abdominal wall and
      the subperitoneal extraperitoneal space to the pelvis. In the extraperitoneal
      tissue, condensation fascias delineate peri- and parasplanchnic spaces. The
      former are between organs and condensation fasciae, the latter between this
      fascia and investing fascia of neighboring muscles of the wall. Thus, perirenal
      space is encircled by renal fascia, and pararenal is exterior to renal fascia.
      Similarly for the urinary bladder, paravesical space is between the umbilical
      prevesical fascia and fascia of the pelvic wall muscles-the prevesical space is
      its anterior part, between transversalis and umbilical prevesical fascia. For the
      rectum, the "mesorectum" describes the extraperitoneal tissue bound by the
      mesorectal condensation fascia, and the pararectal space is between the latter
      and the muscles of the pelvic wall. Perisplanchnic spaces are closed, except for
      neurovascular pedicles. Prevesical and pararectal (presacral) and posterior
      pararenal spaces are in the same anatomical level and communicate. Anterior to
      the anterior layer of the renal fascia, the anterior interfascial plane
      (superimposed and fused mesenteries of pancreas, duodenum, and colon) permits
      communication across the midline. Thus parasplanchnic extraperitoneal spaces of
      abdomen and pelvis communicate with each other and across the midline.

PMID- 20135938
TI  - The association of race and survival from sepsis after injury.
AB  - Genetic variation is associated with outcome disparity in critical illness. We
      sought to determine if race is independently associated with the development of
      posttraumatic sepsis and subsequent related mortality. Our Intensive Care Unit
      database was queried for admissions from January 1, 2000 to June 30, 2007.
      Patients were prospectively followed for sepsis (Any four of the following
      symptoms: temperature > or =38 degrees C, heart rate (HR) > or =90 b/m, RR > or
      =20 b/m (or PaCO2 < or =32 mm Hg), white blood cell count (WBC) > or =12, or
      vasopressor requirement all with an infectious source). White, Black, Hispanic,
      and Asian groups were defined. "Other" race was excluded. Most of the 3998 study
      patients were male (3157, 79.0%). Blunt trauma (2661, 66.6%) predominated. Six
      hundred-seventy-seven (16.9%) met sepsis criteria. Mortality was 14.0 per cent
      (560). Sepsis was increased in Asians versus all others combined (23.7% vs.
      16.1%). Race was independently associated with sepsis (adjusted odds ratio (OR)
      1.12 (1.01-1.24), P value = 0.03). Sepsis associated mortality was 36.9 per cent
      (250/677). Black race demonstrated an increased survival versus all others after
      sepsis (25.4% vs. 37.7%) but this was not statistically significant (adjusted OR
      0.96 (0.73-1.18), P value = 0.71). Race is independently associated with
      posttraumatic sepsis and possibly subsequent sepsis associated mortality. Further
      related study is needed with the ultimate goal of genetically based treatments
      for the prevention and treatment of sepsis after injury.

PMID- 20135939
TI  - Trauma attending physician continuity: does it make a difference?
AB  - Continuity of care is important in achieving optimal outcomes in trauma patients,
      but the optimal length of the trauma attending (TA) rotation is unknown. We
      hypothesize that longer TA rotations provide greater continuity, and therefore
      improve outcomes. We did a retrospective comparison of trauma patient outcomes
      from two consecutive 6-month periods during which we transitioned from a 1-month
      TA rotation to a 1-week TA rotation. The Wilcoxon rank sum test, and the chi2
      were used for statistical analysis. Over the 12-month study period 1924 patients
      were admitted to the Trauma Service. The two groups were similar with regard to
      age, gender, injury mechanism, Injury Severity Score and Glasgow Coma Scale
      scores, and Abbreviated Injury Scores for the chest, abdomen, and extremities.
      Although mortality, patient charges, and violations of the standard of care were
      similar between the two groups, overall morbidity was lower (18.6% vs. 23.2%),
      and hospital length of stay higher (9.07 days vs. 8.41 days) in the 1-week TA
      group compared with the 1-month TA group. A one-week TA rotation was associated
      with a longer hospital length of stay, but improved morbidity. Longer TA
      rotations do not necessarily provide improved continuity or improved outcomes.

PMID- 20135940
TI  - Cognitive performance of morbidly obese patients seeking bariatric surgery.
AB  - Bariatric surgery is efficacious for the treatment of severe obesity; however,
      little empirical research exists describing the demographic, psychosocial, and
      cognitive characteristics of patients presenting for the surgery. One hundred and
      sixty-nine morbidly obese patients seeking bariatric surgery underwent a
      presurgical psychological assessment, including cognitive testing. Morbidly obese
      individuals seeking bariatric surgery were similar in education, income status,
      and IQ compared with normative data. IQ was average, did not correlate with body
      mass index, and reflected a normal distribution. As a group, bariatric surgery
      patients endorsed minimal levels of depression and low levels of psychopathology.
      Obese individuals did demonstrate specific cognitive deficits on tests of
      executive function (e.g., problem solving and planning) when compared with
      normative data. This data suggests that bariatric surgery patients differ very
      little from other surgical populations on most demographic and psychosocial
      variables. The data does provide evidence for specific cognitive deficits in the
      area of executive functions at baseline in morbidly obese adults seeking
      bariatric surgery.

PMID- 20135941
TI  - Running out of gas but not trauma patients: the effect of the price of gas on
      trauma admissions.
AB  - As fuel costs steadily rise and motor vehicle collisions continue to be a leading
      cause of morbidity and mortality, we examined the relationship between the price
      of gasoline and the rate of trauma admissions related to gasoline consumption
      (GRT). The National Trauma Registry of the American College of Surgeons data of a
      rural Level I trauma center were queried over 27 consecutive months to identify
      the rate of trauma admissions/month related to gas utilization compared with the
      number of nongasoline related trauma admissions, based on season and day of the
      week. The average price/gallon of regular gas in our region was obtained from the
      NorthCarolinaGasPrices. com database. A log linear model with a Poisson
      distribution was created. No significant association exists between the average
      price/gallon of gasoline and the GRT rate across the months, seasons, and weekday
      and weekend periods. As the price of gas continues to rise, the rate of rural GRT
      does not decrease. Over a longer period of time and with skyrocketing prices,
      this relationship may not hold true. These findings may also be explained by the
      rural area where limited alternative transportation opportunities exist and a
      trauma patient population participating in high risk behavior regardless of cost.

PMID- 20135942
TI  - 'Normal' vital signs belie occult hypoperfusion in geriatric trauma patients.
AB  - Base deficit (BD) and lactic acid (LA) are accepted markers of hypoperfusion and
      predictors of outcome in the trauma patient and we aim to assess the value of
      these markers in the triage of the elderly with "normal" vital signs. Patients
      older than age 65 who presented between 1997 and 2004 but who did not have
      isolated head injuries were included. Three patient groups were established:
      normal, occult hypoperfusion (OH), and shock. Outcome measures included
      mortality, hospital length of stay, intensive care unit length of stay, and
      discharge disposition. One hundred six patients were included in the analysis and
      had similar Injury Severity Scores. Mean systolic blood pressure was similar in
      the normal and OH groups. Forty-two per cent of patients had abnormal BD or LA in
      the emergency room indicating OH. These patients were more likely to have a
      longer intensive care unit length of stay (8.6 days vs. 3 days; P = 0.01) and
      were also more likely to be discharged to a nursing facility (P = 0.03). The
      trend was toward increased mortality in the OH group. OH is a common finding in
      elderly trauma patients. Outcomes in these patients are different and more like
      those presenting in shock.

PMID- 20135943
TI  - The 'Whip-Stow' procedure: an innovative modification to the whipple procedure in
      the management of premalignant and malignant pancreatic head disease.
AB  - Pancreaticoduodenectomy (PD) is the standard of care in the treatment of
      premalignant and malignant diseases of the head of the pancreas. Variability
      exists in anastomosis with the pancreatic remnant. This work describes a safe and
      easy modification for the pancreatic anastomosis after PD. Ten patients underwent
      the "Whip-Stow" procedure for the management of the pancreatic remnant. PD
      combined with a Puestow (lateral pancreaticojejunostomy [LPJ]) was completed
      using a running single-layer, 4-0 Prolene obeying a duct-to-mucosa technique. LPJ
      and pancreaticogastrostomy (PG) historical leak rates are reported to be 13.9 and
      15.8 per cent, respectively. Mortality, leak, and postoperative bleeding rates
      were 0 per cent in all patients. The Whip-Stow was completed without loops or
      microscope with a 4-0 single-layer suture decreasing the time and complexity of
      the anastomosis. Average time was 12 minutes as compared with the 50 minutes of a
      5 or 6-0 interrupted, multilayered duct-mucosa anastomosis. Benefits included a
      long-segment LPJ. In this study, the Whip-Stow procedure has proven to be a safe
      and simple approach to pancreatic anastomosis in selected patients. This new
      technique provides the benefit of technical ease while obeying the age old
      principles of obtaining a wide duct to mucosa anastomosis.

PMID- 20135944
TI  - Mannequin simulation improves the confidence of medical students performing tube
      thoracostomy: a prospective, controlled trial.
AB  - This study was undertaken to determine the educational benefits of mannequin
      simulation for performance of tube thoracostomy in a porcine model by medical
      students. Thirty medical students were randomized into two groups; the first
      performed tube thoracostomy on a mannequin simulator and then a porcine model;
      the second used only the porcine model. Performance measures included completion
      of subtasks, time to perform the procedure, a global score assigned by faculty
      raters, and a self-evaluation survey. Subtask completion rate was similar in both
      groups (P > 0.05). Mean time to perform the procedure was 9.8 minutes (+/- 0.9,
      simulator), and 9.3 minutes (+/- 1.0, nonsimulator, P > 0.05). Global scores were
      12.3 (+/- 1.3, simulator) and 11.0 (+/- 1.4, non-simulator, P > 0.05). Self
      evaluation of confidence (1 = "very", 7 = "not at all") showed the simulator
      group was significantly more confident (3.4 +/- 0.42) than the nonsimulator group
      (4.7 +/- 0.49, P < 0.05). All students met basic competencies to perform tube
      thoracostomy. The simulator group felt significantly more confident to
      subsequently perform the procedure on a patient, whereas performance was not
      statistically significantly different for the two groups. Further trials may be
      needed to delineate the optimal role for these simulators in teaching tube
      thoracostomy.

PMID- 20135945
TI  - A rare nonmalignant mass of the pancreas: case report and review of pancreatic
      sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology affecting
      patients from all genetic backgrounds. Pancreatic involvement is rare; the first
      case was described on autopsy in 1937. We present a case of pancreatic
      sarcoidosis without a history of the disease presenting as biliary obstruction
      mimicking pancreatic malignancy. We also review the literature with respect to
      management and outcomes of similar cases. The patient described here presented
      with all the signs and symptoms of a pancreatic malignancy, which was confirmed
      on a CT scan; the positron emission tomography scan and the CA 19-9 level were
      also confirmatory of the suspected diagnosis. In this setting, if the mass looks
      resectable, a Whipple procedure would be the next logical step. However, such
      strategy would be aggressive management for a benign condition that could be
      palliated with diverting rather than resective procedures without changing the
      outlook of the disease. We suggest keeping a high index of suspicion in patients
      with a history of the disease if demographic concordance exists.

PMID- 20135946
TI  - Transition from chief residency to specialty training: issues and solutions.
AB  - Three fourths of chief residents in general surgery receive further specialty
      training. The end to start-of-year transition can create administrative conflicts
      between the residency and the specialty training program. An Internet-based
      questionnaire surveyed general surgery and surgical specialty program directors
      to define issues and possible solutions associated with end to start-of-year
      transitions using a Likert scale. There was an overall response rate of 17.5 per
      cent, 19.6 per cent among general surgery directors, and 15.8 per cent among
      specialty directors. Program directors in general surgery felt strongly that the
      transition is an administrative problem (P < 0.001). They opposed extra days off
      at the end of the chief resident year or ending in mid-June, which specialty
      directors favored (P < 0.001). Directors of specialty programs opposed starting
      the year 1 or 2 weeks after July 1, a solution that general surgery directors
      favored (P < 0.001). More agreement was reached on whether chief residents should
      take vacation week(s) at the end of the academic year, having all general surgery
      levels start in mid-June, and orientation programs in July for specialty
      trainees. Program directors acknowledge that year-end scheduling transitions
      create administrative and patient care problems. Advancing the start of the
      training year in mid-June for all general surgery levels is a potential solution.

PMID- 20135947
TI  - An immunohistochemical study of osteopontin in pigment gallstone formation.
AB  - Mucin glycoproteins from the gallbladder epithelium are thought to contribute to
      the matrix or nucleus of gallstones and other biomineralization systems. The
      involved acidic glycoproteins have been reported in bile and gallstones. In
      addition, osteopontin (Opn) is a noncollagenous acidic bone matrix glycoprotein
      that possesses calcium-binding properties. To investigate the role of Opn in
      pigment gallstone formation, the involvement of Opn in pigment gallstone
      formation was studied immunohistochemically in the gallbladder wall and in the
      stones. Staining for Opn was strongly positive in the epithelium of stone-laden
      gallbladders and in their stones. The stone-laden gallbladders were infiltrated
      by macrophages, which intensely stained for Opn. Sections of the pigment stones,
      under low magnification, showed a lamellar pattern of Opn immunolabeling and
      showed a reticular pattern under high magnification. Our results indicate that
      Opn, an acidic glycoprotein from the gallbladder epithelium, seems to be involved
      in lithiasis. Opn from macrophages and/or the epithelium seems to help form the
      matrix protein.

PMID- 20135948
TI  - Management of complex abdominal wall defects using acellular porcine dermal
      collagen.
AB  - Multiple techniques have been used for the repair of complex abdominal wall
      defects after recurrent incisional hernias with varying rates of success. Primary
      repair has been associated with high recurrence rates, and prosthetic mesh
      placement is contraindicated in contaminated surgical fields. The development of
      biologic prostheses has changed the approach to these difficult problems. This
      study evaluates the management of complex abdominal wall defects using acellular
      porcine dermal collagen. Between August 2006 and May 2007, 18 patients underwent
      abdominal wall reconstruction for complex defects with acellular porcine dermal
      collagen (CollaMend; Bard Inc., Warwick, RI). Patient demographics, preoperative
      risk factors, previous herniorrhaphy attempts, postoperative complications,
      recurrences, and long-term results were retrospectively reviewed. Records were
      reviewed at a mean follow up of 7.3 months; the recurrence rate was 44.4 per
      cent. A total of 38.9 per cent (seven of 18) developed a postoperative wound
      complications, including infection in 22.2 per cent (four of 18). All of the
      patients with infection required prosthesis removal as a result of encapsulation
      rather than incorporation of the biologic prosthesis. Acellular porcine dermal
      collagen has the potential for reconstruction of abdominal wall defects with
      postoperative wound occurrences comparable with other biologic materials.
      Encapsulation of the material was a major problem in cases with wound infection
      that required graft removal rather than local wound measures. Hernia recurrence
      and dehiscence of the graft were problems in noncompromised surgical fields.

PMID- 20135949
TI  - Mortality and management of 96 shark attacks and development of a shark bite
      severity scoring system.
AB  - Humans share a fascination and fear of sharks. We predict that most shark attacks
      are nonfatal but require skilled, timely medical intervention. The development of
      a shark bite severity scoring scale will assist communication and understanding
      of such an injury. We retrospectively reviewed records of the prospectively
      maintained International Shark Attack File (ISAF) at the University of Florida.
      The ISAF contains 4409 investigations, including 2979 documented attacks, 96 of
      which have complete medical records. We developed a Shark-Induced Trauma (SIT)
      Scale and calculated the level of injury for each attack. Medical records were
      reviewed for the 96 documented shark attack victims since 1921. Calculated levels
      of injury in the SIT Scale reveal 40 Level 1 injuries (41.7%), 16 Level 2
      injuries (16.7%), 18 Level 3 injuries (18.8%), 14 Level 4 injuries (14.6%), and
      eight Level 5 injuries (8.3%). The overall mortality of shark attacks was 8.3 per
      cent. However, SIT Scale Level 1 injuries comprised the greatest percentage of
      cases at 41.7 per cent. Injury to major vascular structures increases mortality
      and necessitates immediate medical attention and definitive care by a surgeon.
      Shark bites deserve recognition with prompt resuscitation, washout, debridement,
      and follow up for prevention of infection and closure of more complex wounds.

PMID- 20135950
TI  - Extraluminal rectal mucocele resulting from bowel sequestration at the
      anastomotic site after sigmoidectomy.

PMID- 20135951
TI  - Rectal perforation by retroflexion of the colonoscope managed by endoclip
      closure.

PMID- 20135952
TI  - Primary torsion of the omentum and epiploic appendix in children.

PMID- 20135953
TI  - Pneumoretroperitoneum secondary to colonoscopy.

PMID- 20135954
TI  - Persistent anterior mediastinal mass in a patient with Graves' disease.

PMID- 20135955
TI  - Preoperative transjugular intrahepatic portosystemic shunt for extrahepatic
      surgery in cirrhosis.

PMID- 20135956
TI  - Pancreatic tail injury in a patient with chronic pancreatitis secondary to a
      remote traumatic crush injury.

PMID- 20135957
TI  - Sclerosing sweat duct carcinoma in the left axilla presenting as metastatic
      breast cancer.

PMID- 20135958
TI  - Recurrence of midgut volvulus after a Ladd procedure.

PMID- 20135959
TI  - Primary embryonal rhabdomyosarcoma of the prostate in an adult.

PMID- 20135960
TI  - [Artificial total hip arthroplasty with collum femoris preserving for treating
      hip joint].
AB  - OBJECTIVE: To evaluate the therapeutic outcome of artificial total hip
      arthroplasty (THA) with collum femoris preserving for hip joint disease in young
      and middle-aged patients. METHODS: From March 2002 to March 2005, 26 cases (31
      hips) of hip joint disease were treated with artificial THA with collum femoris
      preserving, including 19 males (23 hips) and 7 females (8 hips) and aged 32-48
      years with an average of 37 years. In 31 hips, 17 left hips and 14 right hips
      were involved. There were 9 cases of osteoarthritis of the hip joint caused by
      avascular necrosis of the femoral head (ANFH), 7 cases of ANFH, 3 cases of
      femoral head necrosis caused by dysplasia of acetabular, 1 case of osteoarthritis
      of the hip joint caused by ankylosing spondylitis, and 2 cases of rheumatoid
      arthritis; the course of disease was 2-11 years (5.6 years on average). Two cases
      of femoral neck fracture (Garden IV), and 2 cases of non-union femoral neck
      fractures (1 for Garden III and 1 for Garden IV), the course of disease was 5
      days, 24 months, and 26 months. The prime symptoms were pain, difficult walk and
      limp. All patients were taken X-ray to exclude osteoporosis. RESULTS: The right
      distal femur prosthesis of a bilateral patient cracked owing to excessive
      amputation of collum femoris, and fracture healed after symptomatic treatment.
      All the incisions healed by first intention and no complications occurred. All
      patients were followed up for 4-7 years, with an average of 5.6 years. One case
      had poor hip function because he did not follow rehabilitation procedure, and the
      others achieved good outcome with normal gait. One case complained of persistent
      pain 6 months after operation, and was relieved by administration of some non
      steroidal anti-inflammatory drugs and anti-osteoporosis drugs 6 months later. The
      X-ray films after operation and at last follow up showed good location of
      prosthesis and no bone resorption. Harris score at last follow-up was 91.31 +/-
      0.77, and it was significantly higher than that before operation (50.88 +/-
      0.90), (P < 0.05). The excellent and good rate was 93.5% (excellent in 11 hips,
      good in 18 hips, and fair in 2 hips). CONCLUSION: Artificial THA with collum
      femoris preserving can retain more bone, be easier for revision, and has an
      excellent outcome.

PMID- 20135961
TI  - [Revision surgery for custom-made tumor prosthesis of knee joint].
AB  - OBJECTIVE: To evaluate the surgical skill, cause of revision, complications,
      prosthetic survival and postoperative function in revision of custom-made tumor
      prosthesis replacement of knee joint. METHODS: The clinical data of 33 patients
      who received prosthetic revision surgery between June 2002 and June 2007 were
      reviewed. There were 17 males and 16 females with an average age of 33.1 years
      (range, 16-67 years). The pathological diagnosis included 17 osteosarcomas, 11
      giant cell tumors, 2 malignant fibrous histiocytomas, 1 chondrosarcoma, 1
      synovial sarcoma, and 1 liposarcoma. The involved locations were distal femur in
      22 cases and proximal tibia in 11 cases. The average interval between first
      prosthetic replacement and revision surgery was 45.3 months (range, 6-180
      months). The reason for revision included local recurrence in 2 cases, deep
      infection in 8 cases, aseptic loosening in 7 cases, periprosthetic fracture in 1
      case, prosthetic stem fracture in 6 cases, and prosthetic hinge failure in 9
      cases. Six patients with deep infection received two-stage revision surgery,
      while the other 27 patients received one-stage revision. Cemented prostheses were
      used in all patients. Allograft prosthetic composite and revisions were used in 2
      patients who had deficit of diaphysis for stem fixation. RESULTS: In 17 patients
      who received both primary prosthetic replacement and revision, the operative time
      was (149.8 +/- 40.5) minutes and (189.9 +/- 43.8) minutes, and the blood loss was
      (605.2 +/- 308.0) mL and (834.1 +/- 429.9) mL for primary prosthetic replacement
      and revision, respectively; all showing statistically significant differences (P
      < 0.05). The mean time of follow-up was 45.1 months (range, 12-76 months).
      Healing between allograft and host bone was obtained in 2 patients with allograft
      prosthetic composite and revision after 1.5 years and 2 years, respectively.
      After revision surgery, 3 patients died of lung metastasis after 12-24 months,
      and other 3 patients having lung metastasis were alive with disease. Nine (30%)
      complications occurred in 30 patients who were alive at last follow-up. The
      complications included wound infection in 2 patients, deep infection in 5
      patients, mechanical problems in 2 patients. Prosthetic failure occurred in 7
      patients (23.3%). The 5-year survival rate of revised prosthesis was 68.6%. The
      Musculoskeletal Tumor Society (MSTS) score at 6 months after revision (73.6% +/-
      14.4%) was significantly improved (P < 0.01) when compared with before revision
      (57.1% +/- 10.6%). CONCLUSION: The main reasons for revision of custom-made tumor
      prosthesis of knee joint were mechanical problems and deep infection. Although
      revision surgery of knee is relatively complicated and has some complications, a
      functional limb could be maintained in most tumor patients.

PMID- 20135962
TI  - [Treatment of patellar fracture with internal fixation combined closed reduction
      with arthroscope aid].
AB  - OBJECTIVE: To explore the surgical method and clinical short-term outcomes of
      internal fixation combined closed reduction with arthroscope aid in treating
      patellar fracture. METHODS: From June 2004 to July 2008, 42 patients with fresh
      simple patellar fracture underwent internal fixation combined closed reduction
      with arthroscope aid, included 28 males and 14 females, aged 16-59 years (35
      years on average). The locations were 19 left knees and 23 right knees. Injury
      was by traffic accident in 21 cases, by falling in 11 cases, by sports in 7 cases
      and by crush in 3 cases. All the patients had fresh closed fracture, including 38
      cases of transverse fracture and 4 cases of stellate fracture. The Lysholm score
      was 68.60 +/- 15.20; the proprioceptive function of the knee joints was (3.72 +/-
      0.12) degrees. The time from injury to operation was 3-42 hours (12 hours on
      average). After the treatment of affiliated injury under the arthroscope,
      patellar fracture was reduced with manipulation method, fracture was fixed with
      tensile force screw or modified tension band. RESULTS: All incisions obtained
      healing by first intention after operation, 42 patients were followed up for 12
      39 months (16 months on average). The X-ray films showed callus at the fracture
      and the smooth cartilage surface 6-9 weeks (7 weeks on average) after operation.
      The flexed motion range of knee joint at last follow-up was at normal range in 38
      cases, was limited in 4 cases. Circumference of suffered limbs 15 cm above the
      patella was the same as normal ones in 23 cases, atrophied 0.7 cm in 19 cases.
      There were no breakage of internal fixation and shift of fracture and
      patellofemoral arthritis at last follow-up. The proprioceptive function of the
      knee joints was (2.06 +/- 0.11) degrees and the Lysholm score was 95.10 +/- 3.92;
      all showing statistically significant differences when compared with preoperation
      (P < 0.05). CONCLUSION: This treatment method has advantages as follows: mini
      wound, early exercises and few complications, which can rinse articular cavity
      and repair the affiliated injury at the same time.

PMID- 20135963
TI  - [Biomechanical effect of anterior cruciate ligament rupture on posterior horn of
      lateral meniscus].
AB  - OBJECTIVE: Anterior cruciate ligament (ACL) is an important forward stable
      structure of knees, when its function impaired, the normal mechanical environment
      of joint will be destroyed. Now, to explore the effect of ACL rupture on the
      posterior horn of lateral meniscus by measuring biomechanics. METHODS: Ten
      specimens of knee joints (5 left and 5 right sides asymmetrically) were donated
      voluntarily from 10 normal fresh adult male cadavers, aged 26-35 years with an
      average of 31.4 years. The straining of lateral meniscus posterior horn in 10
      knee joint specimens before and after resection of ACL were tested when the knee
      joints loaded from 0 to 200 N at a velocity of 0.5 mm per second at 0, 30, 60,
      and 90 degrees of flexion and recorded at the moment when the load was 200 N, the
      ratio of straining before and after resection of ACL were counted. All the
      specimens were anatomied and observed in general so as to find injuries such as
      deformation and tearing in lateral meniscus after test. RESULTS: The straining of
      lateral meniscus posterior horn were as follows: intact ACL group, (-11.70 +/-
      0.95) microepsilon at 0 degree flexion, (-14.10 +/- 1.95) microepsilon at 30
      degrees flexion, (-20.10 +/- 1.20) microepsilon at 60 degrees flexion, and (
      26.50 +/- 1.58) microepsilon at 90 degrees flexion; ACL rupture group, (-6.20 +/-
      1.55) microepsilon at 0 degree flexion, (-26.30 +/- 1.89) microepsilon at 30
      degrees flexion, (-37.70 +/- 1.64) microepsilon at 60 degrees flexion, and (
      46.20 +/- 2.78) microepsilon at 90 degrees flexion. There were significant
      differences between intact ACL group and ACL rupture group (P < 0.05). The
      straining ratio of the posterior horn of lateral meniscus rupture ACL to intact
      ACL were 0.53 +/- 0.12, 1.90 +/- 0.31, 1.88 +/- 0.15, and 1.75 +/- 0.16 at 0, 30,
      60, and 90 degrees of flexion. The lateral meniscus were intact in general and no
      injuries such as deformation and tearing were found. CONCLUSION: ACL has a
      significant biomechanical effect on posterior horn of lateral meniscus.
      Consequently, the posterior horn of lateral meniscus is overloaded with ACL
      rupture at 30, 60, and 90 degrees of flexion, and thereby, it will have the high
      risk of tear.

PMID- 20135964
TI  - [Morphology and immunohistochemistry of traumatic and non-traumatic necrosis of
      the femoral head].
AB  - OBJECTIVE: To comprehend the pathological features and possible pathogenesis ot
      avascular necrosis of the femoral head (ANFH) by morphology and
      immunohistochemical observation of osterix (OSX) and adiponectin through in vitro
      traumatic and non-traumatic ANFH specimens, so as to provide a theoretical basis
      for clinical treatment. METHODS: Sixty-six ANFH specimens were collected from 66
      clinical cases undergoing hip replacement surgery. Twenty-four cases of traumatic
      ANFH (group A) included 17 males and 7 females, aged 21 to 70 years with an
      average of 56.5 years; 23 cases of steroid-induced ANFH (group B) included 16
      males and 7 females, aged 56 to 72 years with an average of 61 years; and 19
      cases of alcoholic ANFH (group C) were males, aged 55 to 67 years with an average
      of 58.5 years. Bone tissue was got from weight-bearing and non-weight-bearing
      area of the femoral head respectively. The basic pathological changes was
      observed by HE staining under the optical microscope, and the percentage of empty
      bone lacuna and the percentage of trabecular bone area were calculated. The
      morphological changes of ANFH in different groups were observed by scanning
      electron microscope (SEM). OSX and adiponectin expression were detected by
      immunohistochemical technique. RESULTS: Gross of the femoral head surface in each
      group was rough, collapse, articular cartilage loss, osteophyte formation; cross
      section: dark red in group A, and yellow in groups B and C. HE staining showed
      that weight-bearing area of ANFH have similar morphological features in three
      groups. In non-weight-bearing area of groups B and C, the fat cells in bone
      marrow markedly increased and were hypertrophic; however there were more fibrous
      tissue in group A. There were statistically significant differences (P < 0.001)
      in the percentage of empty bone lacuna of the weight-bearing and non-weight
      bearing area among three groups. There were no statistically significant
      differences (P > 0.05) in the percentage of trabecular bone area among three
      groups. The SEM observation showed that three groups had similar pathological
      changes. Brown granules for OSX and adiponectin positive substance were mainly
      located in the osteoblast of bone marrow of the femoral head. There was
      statistically significant difference (P < 0.05) in the average absorbency (A)
      value of OSX between group A and groups B, C, but there was no statistically
      significant difference (P > 0.05) between groups B and C. While there was no
      statistically significant difference (P > 0.05) in the A value of adiponectin
      among three groups. CONCLUSION: Hormones and alcohol necrosis have more obviously
      fatty degeneration, but the repair capacity of traumatic femoral head necrosis is
      stronger than that of hormones and alcohol necrosis. Alcohol and hormones have
      inhibitory action on the OSX-mediated osteogenic differentiation. Hormones and
      alcohol may not affect osteoblast expressing adiponectin and its receptors.

PMID- 20135965
TI  - [Pulmonary function changes after operation in patients with severe scoliosis].
AB  - OBJECTIVE: To evaluate pulmonary function changes in patients with severe
      scoliosis undergoing anterior release, posterior segmental fixation and fusion,
      and convex thoracoplasty by resecting a short length of rib. METHODS: From
      January 2006 to July 2007, 16 patients with severe scoliosis were treated with
      anterior release, posterior segmental fixation and fusion, and convex
      thoracoplasty by resecting a short length of rib. There were 6 males and 10
      females with an average age of 16.9 years (range, 10-24 years). There were 1 case
      of Lenke 1 curve, 9 cases of Lenke 2 curve, and 6 cases of Lenke 4 curve. The
      preoperative Cobb angle was (104.8 +/- 10.9) degrees and the preoperative
      thoracic kyphotic angle was (30.0 +/- 4.2) degrees. The preoperative height of
      "razor back" deformity was (5.9 +/- 1.2) cm. Before operation, the actual value
      of forced vital capacity (FVC) was (2.04 +/- 0.63) L and that of forced
      expiratory volume in 1 second (FEV1.0) was (1.72 +/- 0.62) L. The percentage of
      actual values to expected ones in FVC was 70% +/- 16%, and that in FEV1.0 was 67%
      +/- 15%. All patients had pulmonary function tests before operation and 3, 6, 12,
      24 months after operation. RESULTS: All wounds healed by first intention. The
      Cobb angle at 24-month follow-up was (53.4 +/- 18.6) degrees and the correction
      rate was 49.0% +/- 15.3%. The thoracic kyphotic angle at 24-month follow-up was
      (34.0 +/- 2.4) degrees and the correction rate was 13.3% +/- 2.2%. The height of
      "razor back" deformity at 24-month follow-up was (2.2 +/- 0.8) cm. Compared with
      preoperative level, all these data showed significant differences (P < 0.05). At
      3 and 6 months, the actual values of FVC and FEV1.0 declined, but no significant
      difference was found (P > 0.05). At 12 and 24 months, the actual values of FVC
      and FEV1.0 were close to the preoperative level (P > 0.05). The percentages of
      actual values to expected ones in FVC and FEV1.0 indicate continued improvement
      in pulmonary function from the postoperative 3 to 24 months follow-up. Compared
      with preoperative level, the percentages of actual values in FVC declined 19% 3
      months postoperatively (P < 0.05) and 12% 6 months postoperatively (P < 0.05).
      The percentages of actual values to expected ones in FEV1.0 declined 16% 3 months
      postoperatively (P < 0.05), and 10% 6 months postoperatively (P < 0.05). The
      percentages of actual values to expected ones in FVC and FEV1.0 were close to the
      preoperative level 12 and 24 months after operation (P > 0.05). CONCLUSION: In
      severe scoliosis patients who are treated with anterior release, posterior
      segmental fixation and fusion, and convex thoracoplasty by resecting a short
      length of rib, pulmonary function decreases obviously 3-6 months after operation.
      And it returns to the operative baseline 12-24 months after operation.

PMID- 20135966
TI  - [Correlative factor analysis of complications resulting from cement leakage after
      percutaneous kyphoplasty in treatment of osteoporotic vertebral body
      compression].
AB  - OBJECTIVE: To explore the correlative factors affecting the complications
      resulting from cement leakage after percutaneous kyphoplasty (PKP) in the
      treatment of osteoporotic vertebral body compression fractures (OVCF). METHODS:
      From February 2005 to October 2008, 71 patients with OVCF were treated by PKP and
      were retrospectively analyzed. There were 16 males and 55 females, and the
      average age was 71.5 years (range, 52-91 years). The average duration of disease
      was 5.7 months (range, 1-11 months). A total of 171 vertebra were involved in
      fracture including 19 cases of single vertebral fractures, 21 cases of double
      vertebral fractures, 20 cases of three vertebral fractures, and 11 cases of more
      than three vertebral fractures. All the treated vertebra were divided into acute
      (86 vertebra) or subacute (85 vertebra) state based on changes in MRI signal
      intensity. There was no radiculopathy or myelopathy. The average injected cement
      volume was 4.6 mL (range, 1.5-6.5 mL). The treatment efficacy was assessed by
      observing the change in anterior and middle vertebral column height, Cobb angle,
      visual analogue scale (VAS) and Oswestry functional score at preoperation, 3 days
      after operation and last follow-up. The patients were divided into cement leakage
      group and no cement leakage group. All the complications were recorded, and then
      the correlative factors affecting the complications were analyzed. RESULTS: All
      the cases had rapid and significant improvement in back pain following PKP. All
      patients were followed up for 14 months (range, 7-18 months). There was no cement
      extravasation resulting in radiculopathy or myelopathy. Four patients (5.63%) had
      lung-related complications. During the follow-up, 9 recurrence vertebral
      fractures were observed in 6 patients (8.45%). The anterior and middle vertebral
      column height, Cobb angle, VAS and Oswestry score were significantly improved
      when compared with preoperation (P < 0.05). Cement leakage occurred in 17 (9.94%)
      vertebral bodies; of 17 cases, the cement leaked into the paravertebral space in
      7 cases, intervertebral space in 6 cases, channel of needling insertion in 3
      cases, and spinal canal in 1 case. Univariate analysis showed statistically
      significant differences (P < 0.05) in preoperative anterior and middle vertebral
      column height, injected cement volume and vertebral body wall incompetence
      between the cement leakage group and no cement leakage group. There were no
      significant differences (P > 0.05) in preoperative Cobb angle, freshness of
      vertebral fracture, location of operative vertebrae and operative approach
      between the two groups. Multiple logistic regression analysis showed that the
      injected cement volume [odds ratio (OR)=3.105, 95% confidence interval (CI) =
      1.674-5.759, P < 0.01] and vertebral body wall incompetence (OR = 11.960, 95% CI
      = 3.512-40.729, P < 0.01) were the predominant variable associated with the
      complications resulted from cement leakage. CONCLUSION: The injected cement
      volume and vertebral body wall incompetence were the factors affecting the
      complications. The improvement of surgical technique is the capital factor that
      may reduce the complications in the PKP.

PMID- 20135967
TI  - [Comparative study on indirect decompression versus open decompression to
      vertebral canal in treating thoracolumbar burst fractures without neurologic
      deficit].
AB  - OBJECTIVE: To compare the clinical effects of indirect decompression versus open
      decompression to vertebral canal in treatment of thoracolumbar burst fractures
      without neurologic deficit. METHODS: From April 2004 to June 2008, 52 cases of
      thoracolumbar burst fracture without neurologic deficit underwent posterior
      exposition, reduction and fixation with Atlas Fixator (AF) instrumentation. There
      were 34 males and 18 females with an average age of 43.1 years (range, 31-63
      years). The affected locations were T11 in 5 cases, T12 in 24 cases, L1 in 16
      cases, and L2 in 7 cases. The time from injury to operation was 3-8 days (4.4
      days on average). All cases were divided into indirect decompression group (group
      A) and open decompression group (group B). There were no statistically
      significant differences (P > 0.05) in sex, age, affect site, and disease course
      between two groups. The operative time, blood loss were recorded. Preoperatively,
      immediately postoperatively and at last follow-up, the height of the fracture
      vertebra and the Cobb angle were obtained from X-ray pictures and were
      statistically analysed. Radiographic parameters on computed tomography (CT)
      pictures were used to get the encroachment rate of vertebral canal. RESULTS: The
      operative time was (87.3 +/-7.9) minutes and (125.3 +/- 13.6) minutes, and the
      blood loss was (273.7 +/- 23.4) mL and (512.6 +/- 37.7) mL in groups A and B,
      respectively; showing statistically significant differences (P < 0.05). The
      average follow-up time was 17.4 months (range, 11-31 months) in group A and 19.9
      months (range, 12-33 months) in group B. All wounds achieved primary healing
      postoperatively without deaths and spinal cord injuries. Postoperative
      complications in group B included 3 cases of screws loosening, 1 case of screw
      breakage, and 3 cases of low back pain, and were given symptomatic management.
      There were no statistically significant differences (P > 0.05) in the height of
      the fracture vertebra, the Cobb angle and the encroachment rate of vertebral
      canal preoperatively or postoperatively between two groups. There were
      statistically significant differences (P < 0.05) in the above three parameters
      between preoperation and postoperation in two groups, but there were no
      statistically significant differences (P > 0.05) in the spinal correction between
      two groups. The losing-rate of spinal correction of the height of the fracture
      vertebra and the Cobb angle of group A was lower than group B, showing
      statistically significant differences (P < 0.05). CONCLUSION: The short-term
      results of two decompression styles in treatment of thoracolumbar burst fractures
      without neurologic deficit were satisfactory, but indirect decompression has more
      merits than open decompression: shorter operative time, less blood loss, lower
      losing-rate of spinal correction, and better stabilization of vertebral column.

PMID- 20135968
TI  - [Function reconstruction of anterior and middle column in thoracolumbar spinal
      tuberculosis by one-stage anterior radical debridement].
AB  - OBJECTIVE: To summarize the effect of one-stage anterior debridement of infection
      in function reconstruction of anterior and middle column for the treatment of
      thoracolumbar spinal tuberculosis. METHODS: From January 2001 to January 2007, 65
      patients with thoracolumbar spinal tuberculosis were treated with one-stage
      anterior debridement, decompression, autogenous bone grafts and internal
      fixation. There were 43 males and 22 females with an average age of 40.2 years
      (range, 19-64 years), including 18 cases of thoracic tuberculosis (T(4-l0)), 44
      cases of thoracolumbar tuberculosis (T11-L2) and 3 cases of lumbar tuberculosis
      (L(3-5)). The disease course was 3 months to 10 years (median 10 months). One
      segment was involved in 7 cases, two segments in 54 cases and three segments in 4
      cases. In 14 cases with spinal cord injury, there were 5 cases of grade C and 9
      cases of grade D according to Frankel classification. The kyphotic Cobb angle was
      20-65 degrees (41 degrees on average). RESULTS: The operative time was 120-210
      minutes (170 minutes on average), and the blood loss was 300-1500 mL (600 mL on
      average). Fifty-eight patients were followed up for 1-6 years (23 months on
      average). Abscess occurred in 2 cases at 40 days and 3 months, and healed after
      symptomatic management. The other incisions achieved healing by first intention.
      The X-ray films showed bony fusion 4-12 months (6 months on average) after
      operation. No tuberculosis recurred. At 12 months after operation, pain
      disappeared, and there were 7 cases of grade D and 7 cases of grade E according
      to Frankel classification. The kyphotic Cobb angle was 0-33 degrees (24 degrees
      on average), showing statistically significant difference (P < 0.05) when
      compared with preoperation. CONCLUSION: Early reconstruction of load-bearing
      function and stability of anterior and middle column in the treatment of spinal
      tuberculosis is great significant. The application of one-stage anterior surgery
      with debridement, decompression, autogenous bone grafts and internal fixation in
      the operative treatment of thoracolumbar tuberculosis is safe and effective after
      a rigorous anti-tuberculosis treatment.

PMID- 20135969
TI  - [A comparative study on establishing rabbit intervertebral disc degeneration
      models by three methods].
AB  - OBJECTIVE: The reliable animal model of intervertebral disc degeneration, can
      provide important experimental carrier to research pathogenesis and treatment of
      intervertebral disc degeneration. To establish three kinds of injury induced
      rabbit intervertebral disc degeneration models and to compare the characteristics
      among them by using biochemical and radiological methods. METHODS: Twenty-five
      healthy New Zealand white rabbits (weighing 2.0-2.5 kg) were randomly divided
      into 5 groups (n=5). The L(3, 4), L(4, 5) and L(5, 6) discs in each rabbit were
      used for study. Groups A and B were for annulus puncture with an 18-gauge needle
      and a 22-gauge needle, respectively; group C was for nucleus aspiration; group D
      was for endplate injury and group E was used as a control. The lumbar spinal
      plain radiographs and magnetic resonance images (MRI) were evaluated, the raltive
      height of intervertebral disc was measured and the grades of disc degeneration
      were recorded 2, 4, 8, 16, and 32 weeks after operation. The water and the
      sulfated-glycosaminoglycan (s-GAG) contents of the nucleus were measured after
      sacrifice (randomly choose one rabbit from each group at each time point).
      RESULTS: In groups A, B, C and D, the height of intervertebral space in plain
      radiograph gradually decreased after operation. The anterior bony excrescences of
      vertebral body and varying degrees of calcification of endplate were also
      observed. The signal intensity of disc in T2-weighted magnetic resonance imaging
      decreased with time too. Compared with group E, the significant changes of height
      of intervertebral discs and grades of disc degeneration in MRI occurred at
      different time points within 4 weeks in groups A-D (P < 0.05). The significant
      change in groups C and D occurred earlier than in groups A and B. The water and s
      GAG contents of discs decreased gradually in groups A-D after operation, while
      the significant change occurred at varying time points within 8 weeks compared
      with group E (P < 0.05). The apparent downward trend in groups C and D occurred
      earlier than in groups A and B. CONCLUSION: All three methods are successful in
      inducing intervertebral disc degeneration. The degenerative process induced by
      endplate injury and nucleus aspiration is faster and more severe than that
      induced by annulus puncture.

PMID- 20135970
TI  - [Repair of irregular wounds on thumbs and index fingers with first dorsal
      metacarpal artery-based pedicle dictyo-pattern sublobe flaps].
AB  - OBJECTIVE: To explore the effect of the first dorsal metacarpal artery-based
      pedicle dictyo-pattern sublobe flaps in repairing irregular wounds on thumbs and
      index fingers. METHODS: From December 2006 to March 2009, 15 patients with
      irregular wounds on thumbs and index fingers were treated, including 11 males and
      4 females, with an average age of 31 years (range, 18-48 years). Of them, 6 cases
      of hyperplastic scar of postburn had a 2-25 years course of disease (7.5 years on
      average) and 9 cases of machine injury had a 14-30 days course of disease (20
      days on average). In 8 thumb wounds on palmaris, there were 3 cases of rhomboid
      wounds, 1 case of C-shape wound, and 4 cases of irregular wounds; the area of
      wounds ranged from 4.5 cm x 3.0 cm to 5.5 cm x 4.5 cm and wounds were treated by
      the first dorsal metacarpal artery-based proximate pedicle dictyo-pattern sublobe
      flaps (5 cm x 3 cm to 6 cm x 5 cm). In 7 index fingers wounds on dorsi-fingers,
      there were 3 cases of 2-wounds, 4 cases of irregular wounds; the area of wounds
      ranged from 1.0 cm x 0.5 cm to 2.2 cm x 2.0 cm and wounds were treated by the
      first dorsal metacarpal artery-based distal pedicle dictyo-pattern sublobe flaps
      (1.2 cm x 0.5 cm to 3.0 cm x 2.2 cm). The donor sites were covered with skin
      grafts or sutured directly. RESULTS: All of the flaps survived completely, the
      wound of recipient site healed at stage I. The free skin graft on donor site
      survived completely, the wound of donor site healed at stage I. All cases were
      followed up for 6-12 months (9 months on average). There was good appearance of
      flaps. The two point discrimination was 5-7 mm for the proximate pedicle flaps
      and 9-10 mm for the distal pedicle flaps. The thumbs had digital opposition,
      opposition function, the index fingers had no dysfunction. According to Hand
      Surgery Association Society of Chinese Medical Association Society standard for
      the part function evaluation trial-use of upper limb, the results of the total
      active movement were excellent in 14 cases, and good in 1 case. The line-scar was
      existed at donor site of the case of direct suture, the function of thumb web had
      no dysfunction. CONCLUSION: The first dorsal metacarpal artery-based pedicle
      dictyo-pattern sublobe flaps can repair the irregular wounds on thumbs and index
      fingers. It has reliable blood supply and simple operation.

PMID- 20135971
TI  - [Repair of soft-tissue defects on volar aspect of fingers with medial plantar
      venous flap].
AB  - OBJECTIVE: To investigate the operative procedure and the short-term therapeutic
      effects of medial plantar venous flaps for restoration of soft-tissue defects on
      the volar aspect of fingers. METHODS: From May 2007 to July 2009, 13 cases (15
      fingers) ofvolar soft tissue defects were treated with medial plantar venous
      flaps, including 7 males (9 fingers) and 6 females (6 fingers) with an average
      age of 30 years (range, 17-55 years). Soft tissue defects were caused by electric
      saws in 4 cases (5 fingers), by crush injury in 6 cases (6 fingers), and by
      burned scar removal in 3 cases (4 fingers). The size of soft tissue defects
      ranged from 1.0 cm x 0.9 cm to 5.8 cm x 3.3 cm, included 5 thumbs, 3 index
      fingers, 3 little fingers, 2 ring fingers, and 2 middle fingers. The emergency
      surgical treatment was performed in 10 traumatic cases after 2 to 12 hours (4
      hours on average); and the elective surgical treatment was performed in the other
      3 cases of scar after burn. The 15 medial plantar venous flaps, with size of 1.0
      cm x 1.0 cm to 6.0 cm x 3.5 cm, were harvested to restore defects. Of them, 12
      venous flaps had 1 superficial vein and the other 3 had 2 veins; and the veins of
      13 venous flaps bridged a single digital artery and the veins of the other 2
      flaps bridged both arteries. The donor sites were sutured directly or were
      covered with skin graft. RESULTS: All 15 venous flaps survived completely, and
      the donor and recipient sites healed by first intention. Eleven cases (11
      fingers) were followed up for 2 to 12 months. The texture and color of the flaps
      were similar to those of adjacent normal skin with a satisfactory appearance. The
      two-point discrimination was 6-9 mm. According to criterion for joint junction of
      total active range of motion/total active range of flexion, the results were
      excellent in 10 cases and good in 1 case; the excellent and good rate was 100%.
      CONCLUSION: The medial plantar venous flap has advantages of easy-to-operate,
      rich blood supply and high survival rate. So it is an ideal and reliable choice
      for volar soft tissue defects of fingers.

PMID- 20135972
TI  - [Repair of forefoot skin and soft tissue defect with reverse lateral tarsal
      artery flap].
AB  - OBJECTIVE: To investigate the operative procedure and the clinical results of
      reverse lateral tarsal artery flap in treating forefoot skin and soft tissue
      defect. METHODS: From August 2007 to April 2009, 11 patients with forefoot skin
      and soft tissue defect were treated with reverse lateral tarsal artery flaps,
      including 7 males and 4 females aged from 16 to 60 years (36 years on average).
      Of 11 cases, defects were caused by crash in 5 cases, by grind contusion in 3
      cases and the course disease was 4-12 hours; by tumor extended resection in 3
      cases and the disease course was 3-12 months. There were 5 wounds on the dorsum
      of first metatarsophalangeal joint, 2 on the dorsum of the first toes, and 4 on
      the dorsum of distal part of metatarsal bones. The area of defect ranged from 4
      cm x 2 cm to 6 cm x 5 cm. There were 6 cases of tendon exposure, 4 cases of
      tendon defect with bone exposure, and 1 case of tendon defect with open
      dislocation of metatarsophalangeal joint. The flap was designed with dorsal
      artery of foot as its pedicle. The plantar perforating branch was designed as its
      rotating point. And the flaps were transferred retrogradely to repair the
      forefoot wounds. The flap area ranged from 4.5 cm x 2.5 cm to 6.5 cm x 4.5 cm.
      The lateral dorsal nerve of foot was anastomosed with the nerve in wound area in
      7 cases. Donor site was covered by full thickness skin graft. RESULTS: Partial
      necrosis occurred and was cured by dressing change, followed by skin graft in 2
      cases. The flaps survived and primary healing was achieved in the other 9 cases.
      All the skin grafts of donor site survived and primary healing was achieved after
      operation. All the patients were followed up for 6 months to 2 years, averaged 13
      months. The texture and color of the flap were similar to skin at the recipient
      site. All patients returned to normal in walking and running and no ulceration
      occurred. The two point discrimination was 5-12 mm 6 months after operation in 7
      patients who received nerve anastomosis, while only protective sensation
      recovered partly in the other 4 patients whose cutaneous nerve were not
      anastomosed. CONCLUSION: Reverse lateral tarsal artery flap has the perfect shape
      and its blood vessel is constant. The blood pedicle is thick and long enough when
      transferred retrogradely. The flap is a good choice in the treatment of forefoot
      skin and soft tissue defect.

PMID- 20135973
TI  - [An improved surgical strategy and treatment outcome of dorsal wrist ganglion].
AB  - OBJECTIVE: To investigate the clinical outcome of treating dorsal wrist ganglion
      with an improved surgical strategy by excising the ganglion completely along
      their stalk and repairing the dorsal carpal ligaments under brachial anesthesia.
      METHODS: From March 2005 to January 2007, 34 patients with dorsal wrist ganglion
      were treated and studied retrospectively. There were 14 males and 20 females,
      aged 25-65 years (43 years on average). The left sides were involved in 22 cases
      and right sides in 12 cases. Thirteen cases of relapse received excision for 1 to
      4 times under local anesthesia, with a mean period of 17 months (14 days to 7
      years) from excision to recurrence. Twenty-one patients were first attack cases
      with a mean period of 11 months (15 days to 8 years) from diagnosis to excision.
      The size of the ganglion ranged from 1.5 cm x 1.2 cm to 4.5 cm x 4.0 cm. Now,
      each surgical process was performed under brachial anesthesia, and a pneumathode
      tourniquet was used. In 6 patients, the stalks of ganglion did not invade the
      carpal ligaments, and ganglion was removed completely without immobilization
      after operation. In 28 patients, the stalks of ganglion invaded the carpal
      ligaments, ganglion was excised completely along its stalk to the dorsal carpal
      structure; the ligaments were sutured directly in 16 cases and were repaired with
      adjacent tissue such as the wall of sheathing canal of extensor tendon in 12
      cases. The wrists were immobilised for 3 weeks. RESULTS: Primary wound healing
      was achieved in all incisions. All patients were followed up for 26-36 months
      with an average of 31.5 months. Only 2 cases (5.9%) recurred. The range of motion
      of the wrist remained normal and the symptom of the dorsal wrist was relieved
      slightly. Patients' satisfaction score ranged from 60 to 100, with an average of
      83.8. CONCLUSION: The ganglion should be excised completely together with defect
      repair of dorsal carpal ligament under brachial anesthesia and the wrist
      immobilised for 3 weeks, the recurrence rate will be reduced greatly.

PMID- 20135974
TI  - [Anatomic study on hook of hamate bone].
AB  - OBJECTIVE: To study the hook of hamate bone by anatomy and iconography methods in
      order to provide information for the clinical treatment of injuries to the hook
      of hamate bone and the deep branch of ulnar nerve. METHODS: Fifty-two upper limb
      specimens of adult corpses contributed voluntarily were collected, including 40
      antisepticized old specimens and 12 fresh ones. The hook of hamate bone and its
      adjacent structure were observed. Twenty-four upper limbs selected randomly from
      specimens of corpses and 24 upper limbs from 12 healthy adults were investigated
      by computed tomography (CT) three-dimensional reconstruction, and then related
      data were measured. The measurement results of 24 specimens were analyzed
      statistically. RESULTS: The hook of hamate bone is an important component of
      ulnar carpal canal and carpal canal, and the deep branch of ulnar nerve is
      located closely in the inner front of the hook of hamate bone. The flexor tendons
      of the forth and the little fingers are in the innermost side, closely lie next
      to the outside of the hook of hamate bone. The hamate bone located between the
      capitate bone and the three-cornered bone with wedge-shaped. The medial-, lateral
      , and front-sides are all facies articularis. The hook of hamate bone has an
      approximate shape of a flat plate. The position migrated from the body of the
      hamate bone, the middle of the hook and the enlargement of the top of the hook
      were given the names of "the basis of the hook", "the waist of the hook", and
      "the coronal of the hook", respectively. The short path of the basement are all
      longer than the short path of the waist. The long path of the top of the hook is
      the maximum length diameter of the hook of hamate bone, and is longer than the
      long path of the basement and the long path of the waist. The iconography shape
      and trait of the hook of hamate bone is similar to the anatomy result. There were
      no statistically significant differences (P > 0.05) between two methods in the
      seven parameters as follows: the long path of the basement of the hook, the short
      path of the basement of the hook, the long path of the waist of the hook, the
      short path of the waist of the hook, the long path of the top of the hook, the
      height of the hook, of hamate bone, and the distance between the top and the
      waist of the hook. CONCLUSION: The hook of hamate bone can be divided into three
      parts: the coronal part, the waist part, and the basal part; fracture of the
      hamate bone can be divided into fracture of the body, fracture of the hook, and
      fracture of the body and the hook. Fracture of the hook of hamate bone or
      fracture union can easily result in injure of the deep branch of ulnar nerve and
      the flexor tendons of the forth and the little fingers. The measurement results
      of CT three-dimensional reconstruction can be used as reference value directly in
      clinical treatments.

PMID- 20135975
TI  - [Effects of mannose-6-phosphate on transforming growth factor beta and
      transforming growth factor beta receptor expression of flexor tendon cells].
AB  - OBJECTIVE: By culturing tendon sheath fibroblasts, epitenon tenocytes and
      endotenon tenocytes of rabbits' tendon in vitro, to study the effects of mannose
      6-phosphate on transforming growth factor beta (TGF-beta) peptide and receptor
      expression, and to provide the experimental basis for preventing the tendon
      healing adhesion by mannose-6-phosphate. METHODS: Eight adult New Zealand white
      rabbits, regardless of their gender and weighing 4.0-4.5 kg, were selected.
      Tendon sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes were
      isolated from rabbit flexor tendon and cultured separately. All 3 cells were
      divided into 2 groups at random after cells were adjusted to a concentration of 4
      x 10(4) per well and 1 x 10(4)/mL. The first was the control group without
      supplementation. The experimental group was supplemented with mannose-6
      phosphate. The expressions of TGF-beta and TGF-beta receptor were quantified with
      enzyme-linked immunosorbent assay. The expression of TGF-beta1 mRNA was also
      assessed with in situ hybridization and the expression of TGF-beta1 was assessed
      with immunohistochemistry. RESULTS: The expressions of TGF-beta and TGF-beta
      receptor in experimental group were significantly lower than that in control
      group (P < 0.05). The expression levels of TGF-beta1 and TGF-beta2 decreased in
      descending order of tendon sheath fibroblasts (36.1%, 37.9%), epitenon tenocytes
      (31.0%, 32.1%), and endotenon tenocytes (31.2%, 27.0%). The expression levels of
      TGF-beta3 decreased in descending order of endotenon tenocytes (42.5%), tendon
      sheath fibroblasts (41.2%), and epitenon tenocytes (33.3%). The expression levels
      of TGF-beta receptor 1 and TGF-beta receptor 2 decreased in descending order of
      epitenon tenocytes (29.9%, 26.2%), endotenon tenocytes (27.8%, 23.5%), and tendon
      sheath fibroblasts (23.1%, 20.0%). The expression levels of TGF-beta receptor 3
      decreased in descending order of endotenon tenocytes (26.1%), epitenon tenocytes
      (19.2%), and tendon sheath fibroblasts (15.8%). In experimental group, the
      positive expression of TGF-beta1 mRNA and the expression level of intracellular
      TGF-beta1 mRNA in all 3 tendon cells were significantly lower than those in the
      control group (P < 0.05). Immunohistochemical staining showed the expressions of
      TGF-beta1 in all 3 tendon cells were significantly lower in the experimental
      group than in the control group. CONCLUSION: Mannose-6-phosphate can
      significantly decrease the expressions of TGF-beta peptide, TGF-beta receptor,
      and TGF-beta1 mRNA. Modulation of mannose-6-phosphate levels may provide a mean
      of modulating the effects of TGF-beta on adhesion formation in flexor tendon
      wound healing.

PMID- 20135976
TI  - [Treatment of fresh tossy type III acromioclavicular joint dislocations and neer
      type II distal clavicle fractures with clavicular hook plate].
AB  - OBJECTIVE: To investigate the clinical efficacy, complications and necessity of
      removing internal fixation in treatment of fresh Tossy type III acromioclavicular
      joint dislocations and Neer type II distal clavicle fractures with clavicular
      hook plate. METHODS: From June 2005 to June 2008, 24 patients with fresh Tossy
      type III acromioclavicular joint dislocations and 20 patients with fresh Neer
      type II distal clavicle fractures were treated. There were 32 males and 12
      females with an age range of 18-66 years (38.5 years on average), involving 18
      left shoulders and 26 right shoulders. The injury was caused by traffic accident
      in 31 cases and by falling in 13 cases. The mean time from injury to operation
      was 4 days (range, 2-8 days). All patients were treated by reduction with
      clavicular hook plate fixation. The coracoclavicular ligaments were not sutured.
      The shoulder functions were evaluated according to University of California-Los
      Angeles (UCLA) score system and analysed before and after removing internal
      fixation. RESULTS: Wound infection occurred in 2 cases 1 week after operation and
      healed after symptomatic management, the other incisions healed by first
      intention. One case accepted hook plate fixation again because of loosening
      hooking-up 1 week after operation. One case accepted hook plate removal and
      Kirschner wire fixation because of severe shoulder's pain on the postoperative
      third day. Thirty-eight patients were followed up for 8-32 months (18 months on
      average), there was no plate breakage. Clavicle fractures got bony union after 3
      6 months (4.2 months on average). At last follow-up (before plate removal),
      according to UCLA shoulder function score system, the results were excellent in
      11 cases, good in 22 cases, and fair in 5 cases; the excellent and good rate was
      86.8%. Because of shoulder's pain, plates were removed in 20 patients 3-16 months
      (10 months on average) after operation. The cases were followed up 3-8 months (5
      months on average) after removing plate. No dislocation and fracture occurred
      again. There was statistically significant difference (P < 0.01) in the
      functional scores of shoulder between before (30.55 +/- 4.00) and after removing
      internal fixation (33.85 +/- 1.95). CONCLUSION: Clavicular hook plate fixation is
      an effective treatment for fresh Tossy type III acromioclavicular joint
      dislocations and Neer type II distal clavicle fractures. Normative operating,
      correct plate moulding, functional rehabilitation after operation are key factors
      in preventing complications and reaching good clinical efficacy. For the patients
      with postoperative symptoms, the plate should be removed to improve the
      shoulder's function.

PMID- 20135977
TI  - [Treatment of nonunion of lower segment of humerus with combination of rib flaps
      of cross chest and double plates].
AB  - OBJECTIVE: To evaluate the result of treating nonunion of lower segment of
      humerus with combination of rib flaps of cross chest and double plates. METHODS:
      From February 2000 to May 2006, 21 cases of nounion of lower segment of humerus
      were treated. There were 13 males and 8 females with an average age of 36.5 years
      (range, 17-56 years). According to AO classification, there were 5 cases of type
      A1.3, 7 cases of type B1.3, 6 cases of type B2.3, 2 cases of type B3.3, and 1
      case of type C1.3. All nonunion occurred after internal fixation, which was
      caused by bone resorption at fracture end in 12 cases, by plates breakage in 3
      cases, and by internal fixation loosening in 6 cases; including 8 cases of
      hypertrophic nonunion and 13 cases of atrophy nonunion without pseudoarthrosis.
      An average time of nonunion was 1.5 years (from 8 months to 3 years). All cases
      were treated with combination of rib flaps of cross chest (length, 3.0-3.5 cm)
      and double plates. The pedicle was divided 8 to 10 weeks after operation and all
      cases carried out functional exercise. RESULTS: The patients were followed up for
      an average time of 18.2 months (range, 1-3 years). All nounion of lower segment
      of humerus were healed and no radial nerve injury occurred. Primary healing of
      wound was achieved at both donor and recipient sites. Bony union was achieved in
      all cases after an average time of 3.5 months (range, 3-5 months) after
      operation. According to the the Hospital for Special Surgery (HSS) functional
      elbow index, the average score was 89.3 (range, 81.7-92.5) and the outcome was
      excellent in 14 cases, good in 4 cases, and poor in 3 cases, the excellent and
      good rate was 85.7%. CONCLUSION: Combination of rib flaps of cross chest and
      double plates is an

PMID- 20135978
TI  - [Revision cause and effect of gamma nail fixation].
AB  - OBJECTIVE: To investigate the reasons of failure of Gamma nail treatment for
      intertrochanteric fractures and define operative techniques of the revision
      surgery. METHODS: From January 1999 to January 2008, 20 cases of 432 patients
      treated with Gamma nails for intertrochanteric fractures were revised. There were
      9 males and 11 females, aged 24-87 years (median 65 years). Among them, there
      were 4 cases of femoral shaft fracture, 2 cases of screw penetrating the femoral
      head, 11 cases of screw cutting out the femoral head and neck, 2 cases of
      internal rotation malformation, and 1 case of infection. The operative procedures
      of revision were as follows: 4 cases were treated with the long Gamma nail, 4
      cases by adjusting the position of Gamma nail, 11 cases with artificial femoral
      head replacement, and 1 case by removing Gamma nail and debriding and re-implant
      the Gamma nail. RESULTS: The hospitalization days were 16-28 days (21.2 days on
      average); the bleeding volume during operation was 150-600 mL (380 mL on
      average). All wounds healed by first intention. Bed rest days were 7-15 days
      (12.5 days on average). All the patients were followed up for 1-8 years (5 years
      on average). The operations were successful, the femoral intertrochanteric
      fracture and femoral shaft fracture reached bony union. Complications such as
      loosening, breakage of hardware and coxa adduct were not observed. No loosening
      and dislocation of the prosthesis occurred. Among the patients with
      complications, 9 patients were treated with a Gamma nail again. Fracture healing
      was achieved within 2 to 5 months, with an average of 3 months. According to the
      WANG Fang et al. criterion for hip joint function, the results were excellent in
      7 cases and good in 2 cases. In 11 patients who received artificial femoral head
      replacement, the hip joint function restored to normal. Harris score was 90-93.
      CONCLUSION: Various causes such as osteoporosis, tip-apex distance (> or =25 mm),
      femoral shaft malformation, Gamma nail shortcomings may lead to complications
      after Gamma nail treatment for intertrochanteric fractures. Good results will be
      achieved by different revision techniques.

PMID- 20135979
TI  - [Free anterolateral thigh myocutaneous flap for reconstruction of soft tissue
      defects following en block resection of tongue cancer].
AB  - OBJECTIVE: To evaluate the results of the reconstruction of the soft tissue
      defects following the en block resection of tongue cancer using free
      anterolateral thigh myocutaneous flaps. METHODS: From November 2006 to December
      2008, 109 cases underwent the reconstruction of the soft tissue defects following
      the en block resection of tongue cancer using free anterolateral thigh
      myocutaneous flaps. There were 75 males and 34 females with an age of 23-75 years
      (50.4 years on average). The disease course was 1-6 months. According to 2002
      International Union Control Cancer (IUCC) criterion for TNM stage, there were 35
      cases of T2N0M0, 8 cases of T2N1M0, 2 cases of T2N2M0, 31 cases of T3N0M0, 12
      cases of T3N1M0, 7 cases of T3N2M0, 5 cases of T4N0M0, 4 cases of T4N1M0, 3 cases
      of T4N2M0, and 2 cases of T4N3M0. The range of tongue defect was 5 cm x 3 cm to
      12 cm x 8 cm. The flap area ranged from 7 cm x 4 cm to 20 cm x 8 cm. Eighty-two
      patients with T3, T4 and positive lymph node metastasis determined by
      pathological examination after operation received radiotherapy. The vitality of
      the flaps and the healing of the wounds were observed postoperatively. The shape
      and function of the reconstructed tongue were determined, the influences on
      function at donor site were evaluated and the flap tolerance to radiotherapy was
      investigated during the follow-up period. RESULTS: Mouth floor mandibular fistula
      occurred in 5 cases 5-7 days after operation, seroma formation in 1 case and
      wound dehiscence in another case at the donor site; the wounds healed by
      secondary intention after dressing. The other wounds healed primarily. All 105
      flaps survived completely, 3 flaps developed partial necrosis 3-5 days after
      operation, the wounds healed after dressing; and 1 flap failed 3 days after
      operation, then it was removed and defects was repaired using pectoralis major
      muscle flap. Blisters occurred in 8 flaps (all being thinning flaps) 1 day after
      operation. The overall complete survival of the flap was 96.3% (105/109). The
      patients were followed up for 0.5-2.5 years (1.2 years on average). Although the
      flaps had a little atrophy, the shape of the reconstructed tongue was still
      satisfactory with suitable tongue-mandibular groove. No depression was observed
      in the mandibular region. The speech as well as swallowing function were well
      recovered. The scar was easily hidden with no important functional impairment at
      the donor site. No flap necrosis occurred in all the patients who received
      postoperative radiotherapy. CONCLUSION: Free anterolateral thigh myocutaneous
      flap transplantation is safe and reliable, and it has the advantages of the
      better result at the recipient site, the less morbidity at the donor site, fewer
      postoperative complications and excellent tolerance to radiotherapy. So it is an
      ideal flap to repair soft tissue defects following the en block resection of
      tongue cancer.

PMID- 20135980
TI  - [Repairing defects of rabbit articular cartilage and subchondral bone with
      biphasic scaffold combined bone marrow stromal stem cells].
AB  - OBJECTIVE: To explore the preparing methods in vitro and test the clinical
      applicability of implantation in vivo of bone marrow stromal stem cells (BMSCs)
      biphasic scaffold to repair defects of cartilage and subchondral bone and to
      compare the differences in repaired outcomes of composite, single biphasic
      scaffold and rabbits themselves. METHODS: The upper chondral phase and the lower
      osseous phase of the plugs, using poly-lactic-co-glycolic acid (PLGA),
      hydroxyapatite (HA), and other biomaterials, were fused into carrier scaffold, on
      which collagen type I (Col I) was coated. The surface and inner structure of
      biphasic scaffold were observed under scanning electron microscope (SEM). BMSCs
      was isolated from the bone marrow of tibia and femurs of young New Zealand
      rabbits using centrifuging and washing, and their morphologies and adherences
      were observed everyday. Then BMSCs were inoculated on the surface of scaffold to
      form BMSCs-scaffold composites. Osteochondral defects were surgically created on
      articular surface of femoral intercondylar of 30 New Zealand rabbits, which were
      divided into groups A, B and C. In group A, a biphasic osteochondral composite
      were implanted into defect, BMSCs and biphasic cylindrical porous plug of PLGA-HA
      Col I in group B, and group C was used as a control without implant. Specimens
      were harvested to make macroscopic and histological observations at the 1st, 3rd,
      6th, and 9th months after operation respectively; meanwhile immunohistological
      and micro-computed tomography (micro CT) examinations were performed and graded
      at the 9th month after operation. RESULTS: SEM showed an excellent connection of
      holes in the biphasic scaffold infiltrated by Col I. Optical microscopy and SEM
      showed a good growth of BMSCs in scaffold without obvious cellular morphological
      changes and an accumulation in the holes. Macroscopic samples showed a resistant
      existence of defects of group C within 9 months; the scaffold completely
      degenerated and chondral-like tissue formed on articular surface with partly
      collapses and irregular defects in group A; and smoother surface without
      collapses and approach to normal with texture of new regeneration in group B.
      There were statistically significant differences in macroscopic results (P <
      0.001), group B was superior to group A, and group C was the worst. The micro CT
      showed good repairs and reconstruction of subchondral bone, with a acceptable
      integration with newborn chondral-like tissue and host bone in group B.
      Quantificational analysis of relevant parameters showed no significant
      differences. Histological results showed inflammations located in defects at the
      1st month, new tissue grew into scaffold at the 3rd month; new chondral-like
      tissue crept on the margin of defects and biphasic scaffold degenerated
      completely at the 6th month, and lots of collagen formed in subchondral bone with
      major fibrocartilage on chondral area at the 9th month after surgery in groups A
      and B. In groups A and B, immunohistological observations were weak positive for
      Col II and positive for Col I. CONCLUSION: Biphasic scaffold implanted in body
      can induce and accelerate repair of defects of articular cartilages which are
      mainly filled with fibrocartilage, especially for subchondral bone. Scaffold
      combined with BMSCs has the best repairing effects 9 months after implantation.

PMID- 20135981
TI  - [Effect of acellular process on small intestinal submucosa cell residue and
      growth factor content].
AB  - OBJECTIVE: To investigate the effect of machine-enzyme digestion method on the
      residual quantity of small intestinal submucosa (SIS) cell and the content of
      growth factors. METHODS: Fresh jejunum of pig within 4 hours after harvesting was
      prepared into SIS after machine digestion (removing placenta percreta, mucosa,
      and muscular layer), decrease, trypsinization, abstergent processing, and freeze
      drying. Samples were kept after every preparation step serving as groups A, B, C,
      D, and E, respectively (n=4 per group). And the fresh jejunum served as control
      group (group F, n=4). The histological alteration in each preparation process was
      reviewed with HE staining and scanning electron microscope (SEM). Nest-polymerase
      chain reaction (PCR) was used to determine the content of death associated
      protein 12 (DAP12), and enzyme-linked immunosorbent assay (ELISA) was applied to
      detect the content of vascular endothelial growth factor (VEGF), basic fibroblast
      growth factor (bFGF), transforming growth factor beta (TGF-beta), tumor necrosis
      factor alpha (TNF-alpha). RESULTS: HE staining and SEM observation showed that
      there were residual cells in groups A and B, and there were no residual cells in
      groups C, D, and E. Nest-PCR test revealed the occurrence of DAP12 in each group.
      The contents of DAP12 in groups A, B, C, D, E, and F were (18.01 +/- 9.53),
      (11.87 +/- 2.35), (0.59 +/- 0.27), (0.29 +/- 0.05), (0.19 +/- 0.04), and (183.50
      +/- 120.13) copy x 10(6)/cm2. The content of DAP12 in group F was significant
      higher than that of other groups (P < 0.05), groups A and B was higher than
      groups C, D, and E (P < 0.05), there were significant differences among groups C,
      D, and E (P < 0.05), and there was no significant difference between groups A and
      B (P > 0.05). The ELISA test showed the content of VEGF, bFGF, TGF-beta, and TNF
      alpha in group A was significantly higher than that of groups B, C, D, and E (P <
      0.05), and there was no significant difference among groups B, C, D, and E (P >
      0.05). CONCLUSION: SIS prepared by simple mechanical method has more residual
      cells, while the machine-enzyme digestion method can effectively remove the cells
      and significantly reduce the DAP12 content. This approach can not obviously
      reduce the growth factor content in SIS.

PMID- 20135982
TI  - [Anatomical double bundle reconstruction of medial patellofemoral ligament with
      allograft tendon in patellar dislocations].
AB  - OBJECTIVE: To investigate the clinical therapeutic results of allograft tendon
      for anatomical reconstruction of medial patellofemoral ligament (MPFL) in
      patellar dislocations. METHODS: From September 2005 to June 2008, 20 patients
      with patellar dislocation underwent MPFL reconstructions. There were 4 males and
      16 females, aged 13 to 31 years (19 years on average). Patellar dislocations
      occurred in 7 left and 13 right knees, including 6 cases of acute dislocation and
      14 cases of recurrent dislocation. The disease course was 1 day to 2 years. The
      frequency of dislocation was 1-6 (4 on average). Affected knee joint showed pain,
      swelling and patellar instability; the range of action for patella obviously
      increased. The X-ray films showed patellar dislocation or medial margin avulsion
      fracture. The preoperative Q angle was (15 +/- 3) degrees, the congruence angle
      was (10 +/- 11) degrees. Reconstruction was performed via allograft tendon.
      Allograft tendon was anchored to the superomedial pole of the patella by two bone
      anchors, and the other end was fixed at the natural MPFL insertion site near the
      medial femoral condyle with an interference screw in a bone tunnel. All patients
      were evaluated postoperatively; Kujala patellofemoral scores, objective knee
      function, complications, and reoperations were assessed. RESULTS: Primary healing
      was achieved in 18 cases and secondary healing in 2 cases. No infection or
      necrosis and absorption of grafts was observed. All patients were followed up for
      an average of 25.6 months (range, 6-34 months) postoperatively. At last follow
      up, other patients had no pain, swelling and patellar instability except 1 case;
      neither patella redislocation nor fracture occurred. The X-ray films showed good
      position of anchors and tunnel 6 months after operation, and the congruence angle
      was (3 +/- 8) degrees, showed statistically significant difference when compared
      with preoperation (P < 0.05). The postoperative Q angle was (15 +/- 2) degrees,
      the Kujala knee function score improved significantly from 60.8 +/- 7.2 to 83.4
      +/- 8.0 at last follow-up, showing statistically significant difference (P <
      0.05). According to Insall et al. for function, the results were excellent in 12
      cases, good in 6 cases, and fair in 2 cases, the excellent and good rate was 90%.
      CONCLUSION: MPFL reconstruction improves clinical symptoms. Anatomical MPFL
      reconstruction is effective for patellar dislocation, and it offer good recovery
      of the pre-morbid patella mechanics. There would be little bone loss when tendon
      is fixed by anchors, and there would be less patellar fracture than bone tunnel
      technique. The bone anchors also provide firm fixation. Allograft can avoid the
      graft harvest site morbidity, but it increases the cost of the surgery.

PMID- 20135983
TI  - [Minimally invasive approach for cervical spondylotic radiculopathy].
AB  - OBJECTIVE: To summarize the recent minimally invasive approach for cervical
      spondylotic radiculopathy (CSR). METHODS: The recent literature at home and
      abroad concerning minimally invasive approach for CSR was reviewed and
      summarized. RESULTS: There were two techniques of minimally invasive approach for
      CSR at present: percutaneous puncture techniques and endoscopic techniques. The
      degenerate intervertebral disc was resected or nucleolysis by percutaneous
      puncture technique if CSR was caused by mild or moderate intervertebral disc
      herniations. The cervical microendoscopic discectomy and foraminotomy was an
      effective minimally invasive approach which could provide a clear view. The
      endoscopy techniques were suitable to treat CSR caused by foraminal osteophytes,
      lateral disc herniations, local ligamentum flavum thickening and spondylotic
      foraminal stenosis. CONCLUSION: The minimally invasive procedure has the
      advantages of simple handling, minimally invasive and low incidence of
      complications. But the scope of indications is relatively narrow at present.

PMID- 20135984
TI  - [Bacterial biofilms and chronic osteomyelitis].
AB  - OBJECTIVE: To overview the effect of bacterial biofilms (BBF) on the formation of
      chronic osteomyelitis and the treatment measure. METHODS: The original articles
      in recent years about the relationship between BBF and chronic osteomyelitis were
      reviewed. RESULTS: The diagnosis and treatment of chronic osteomyelitis was very
      difficult, besides hyperplasia of local scar, poor blood supply, drug-resistant,
      forming of BBF also was an important reason. BBF formed on the surface of
      necrosis soft tissue and dead bone. Due to the protection of BBF, the bacterium
      were far more resistant to antimicrobial agents, which caused the recurrence of
      chronic osteomyelitis. The forming of BBF included three processes which were
      adhesion, development and maturity. As the major pathogens of chronic
      osteomyelitis, staphylococcus had its own characteristic. Designing therapeutic
      programmes according to these characteristics had become the trend of anti
      infection treatment of BBF. CONCLUSION: Although there are lots of studies on
      anti-biofilm due to the key factors during the forming of BBF, the most effective
      way of anti-biofilm is still debridement.

PMID- 20135985
TI  - [Current development of basic research and clinical use of small intestinal
      submucosa].
AB  - OBJECTIVE: To summarize the basic research and the clinical use of small
      intestinal submucosa (SIS), which is used as a degradable material for tissue
      repair. METHODS: Recent literature concerning SIS at home and abroad was
      extensively reviewed, and current developments of the basic research and the
      clinical use of SIS were investigated. RESULTS: SIS had many biological
      advantages in tissue repair, and was used to repair various tissue defects in
      animal trials. It had successful outcomes in many clinical trials to repair
      hernia, anal fistula and Peyronie diseases. And it also had good results at the
      early stage to treat dilation of the anastomosis, urethroplasty, hypospadias, and
      other diseases, however, the long-term follow-up was needed. CONCLUSION: SIS is
      one kind of good material for tissue repair, and has promising future in the
      clinical use.

PMID- 20135986
TI  - [Dynamic changes of topsoil organic carbon in subalpine spruce plantation at
      different succession stages in western Sichuan Province].
AB  - Soil samples at 0-30 cm depth were collected from the primary spruce (Picea
      asperata) forest and its plantations at different succession stages (22-, 47-,
      and 65-year-old) in subalpine zone of western Sichuan Province to study the
      dynamic changes of soil organic carbon stock and labile organic carbon content.
      The soil total organic carbon (TOC) stocks in 0-10, 10-20, and 20-30 cm soil
      layers decreased from 95.87, 79.08, and 71.55 t x hm(-2) in 22-year-old
      plantation to 56.12, 34.75, and 31.06 t x hm(-2) in 65-year-old plantation,
      respectively, and the TOC stocks in these soil layers in 47 and 65-year-old
      plantations were less than those (88.08, 71.16 and 64.81 t x hm(-2),
      respectively) in primary forest. The easily oxidizable organic carbon (EOC)
      contents in 0-10, 10-20, and 20-30 cm soil layers decreased from 35.89, 26.91,
      and 26.00 g x kg(-1) in primary forest to 20.25, 14.50, and 12.36 g x kg L(-1) in
      65-year-old plantation, the microbial biomass carbon (MBC) contents decreased
      from 524.44, 273.26, and 257.97 mg x kg(-1) in primary forest to 312.41, 186.95,
      and 152.18 mg x kg(-1) in 65-year-old plantation, and the particulate organic
      carbon (POC) contents decreased from 40.23, 27.10, and 19.55 g x kg(-1) in
      primary forest to 12.33, 7.31, and 5.32 g x kg(-1) in 65-year-old plantation,
      respectively. The results suggested that within the long succession period of
      primary P. asperata forest to its plantations in the subalpine zone of western
      Sichuan Province, soil TOC and labile organic carbon were in the state of net
      consumption.

PMID- 20135987
TI  - [Effects of simulated nitrogen deposition on litter decomposition in
      Neosinocalamus affinis stands in rainy area of West China].
AB  - An in situ experiment was conducted to study the effects of simulated nitrogen
      deposition on the litter decomposition in Neosinocalamus affinis stands in rainy
      area of West China. Four treatments were installed, i.e., null N (CK, 0 kg x hm(
      2) x a(-1)), low N (LN, 50 kg x hm(-2) x a(-1)), medium N (MN, 150 kg x hm(-2) x
      a(-1)), and high N (HN, 300 kg x hm(-2) x a(-1)). Among the litters, leaf had the
      highest decomposition rate, followed by sheath, and twig, with a remaining rate
      after decomposing for 15 months being 26.38%, 46.18%, and 54.54%, respectively (P
      < 0.01). Leaf litter decomposed faster during the first 2 months and the 7th-10th
      month, while the decomposition of sheath and twig was faster from the 5th to the
      8th month. It took 2.573 years to decompose 95% of leaf litter mass, 1.686 years
      and 3.319 years shorter than that of sheath and twig, respectively. After 15
      months decomposition of leaf litter, no significant differences were observed
      among different treatments. To decompose 95% of sheath litter needed 2.679-4.259
      years, being the longest in CK and the shortest in treatment MN. After
      decomposing for 15 months, the decomposition rate of twig litter was in the order
      MN > HN > LN > CK, and significant difference existed between treatments MN and
      LN. Nitrogen deposition had obvious promotion effect on the litter decomposition
      in the N. affinis stands, but this effect decreased with increasing deposited N
      concentration and time extension.

PMID- 20135988
TI  - [Net CO2 exchange and carbon isotope flux in Acacia mangium plantation].
AB  - By using stable carbon isotope technique, the leaf-level 13C discrimination was
      integrated to canopy-scale photosynthetic discrimination (Deltacanopy) through
      weighted the net CO2 assimilation (Anet) of sunlit and shaded leaves and the
      stand leaf area index (L) in an A. mangium plantation, and the carbon isotope
      fluxes from photosynthesis and respiration as well as their net exchange flux
      were obtained. There was an obvious diurnal variation in Deltacanopy, being lower
      at dawn and at noon time (18.47 per thousand and 19.87 per thousand,
      respectively) and the highest (21.21 per thousand) at dusk. From the end of
      November to next May, the Deltacanopy had an increasing trend, with an annual
      average of (20.37 +/- 0.29) per thousand. The carbon isotope ratios of CO2 from
      autotrophic respiration (excluding daytime foliar respiration) and heterotrophic
      respiration were respectively (- 28.70 +/- 0.75) per thousand and (- 26.75 +/-
      1.3) per thousand in average. The delta13 C of nighttime ecosystem-respired CO2
      in May was the lowest (-30.14 per thousand), while that in November was the
      highest (-28.01 per thousand). The carbon isotope flux of CO2 between A. mangium
      forest and atmosphere showed a midday peak of 178.5 and 217 micromol x m(-2) x s(
      1) x per thousand in May and July, with the daily average of 638.4 and 873.2
      micromol x m(-2) x s(-1) x per thousand, respectively. The carbon isotope flux of
      CO2 absorbed by canopy leaves was 1.6-2.5 times higher than that of CO2 emitted
      from respiration, suggesting that a large sum of CO2 was absorbed by A. mangium,
      which decreased the atmospheric CO2 concentration and improved the environment.

PMID- 20135989
TI  - [Design of dynamic simulation system for carbon cycle in forest ecosystem].
AB  - Modeling techniques are indispensable for the researches on the carbon cycle of
      forest ecosystem. In this paper, a new general simulation system FORCASS (FORest
      CArbon Simulation System) was designed and developed under Simulink environment,
      with the objectives of modeling the carbon cycle dynamics of forest ecosystems. A
      comprehensive analysis on the framework, design solution, and development process
      showed that the FORCASS was feasible. This simulation system had the
      characteristics of 1) it divided the carbon storage in forest ecosystem into four
      compartments, i.e., vegetation, litter, soil, and animal, and took into account
      the carbon flows between the compartments, possessing high mechanism and easily
      to be comprehended, 2) it was a process-based system, taking the Richards growth
      function of vegetation component biomass carbon storage as the input to solve
      difference equations, and was easily to export the outputs such as net primary
      productivity (NPP) and net ecosystem productivity (NEP) at different stand ages,
      and 3) it had the explicit expansibility because it was developed based on a
      general framework for carbon cycle patterns.

PMID- 20135990
TI  - [Construction and application of probability distribution model for mixed forests
      measurement factors].
AB  - Aiming at the deficiencies in the researches about the probability distribution
      model for mixed forests tree measurement factors, a joint maximum entropy
      probability density function was put forward, based on the maximum entropy
      principle. This function had the characteristics of 1) each element of the
      function was linked to the maximum entropy function, and hence, could integrate
      the information about the probability distribution of measurement factors of main
      tree species in mixed forests, 2) the function had a probability expression of
      double-weight, being possible to reflect the characteristics of the complex
      structure of mixed forests, and accurately and completely reflect the probability
      distribution of tree measurement factors of mixed forests based on the fully use
      of the information about the probability distribution of measurement factors of
      main tree species in mixed forests, and 3) the joint maximum entropy probability
      density function was succinct in structure and excellent in performance. The
      model was applied and tested in two sampling plots in Tianmu Mountain Nature
      Reserve. The fitting precision (R2 = 0.9655) and testing accuracy (R2 = 0.9772)
      were both high, suggesting that this model could be used as a probability
      distribution model for mixed forests tree measurement factors, and provided a
      feasible method to fully understand the comprehensive structure of mixed forests.

PMID- 20135991
TI  - [Effects of soil moisture condition and phosphorus supply on the seedlings growth
      and phosphorus efficiency of Schima superba provenances].
AB  - Taking four representative Schima superba provenances from Longquan in Zhejiang,
      Jian'ou and Youxi in Fujian, and Ji'an in Jiangxi as test materials, and with the
      S. wallichii from Guangxi as the contrast, a pot experiment was conducted to
      study their seedlings growth and physiological responses under effects of
      different soil moisture condition and phosphorus supply. Significant differences
      were observed in the seedlings growth, root morphological parameters, and
      phosphorus absorption efficiency among the provenances under different soil
      moisture condition and phosphorus supply. The provenances from Jian'ou in Fujian
      and Longquan in Zhejiang exhibited larger growth increment, more developed root,
      and higher phosphorus absorption efficiency, compared with those from Youxi in
      Fujian and Ji'an in Jiangxi, while the S. wallichii from Guangxi Province
      remained its original characteristics of fast growing and drought and infertility
      resistance. Soil moisture condition and phosphorous supply had significant
      effects on the growth and development of S. superba. The seedlings growth, dry
      matter accumulation, root parameters, and phosphorus absorption efficiency were
      18.5%-105.6% higher under appropriate soil moisture condition than under drought
      stress, and 37.5%-286.2% higher under high phosphorus than under low phosphorus
      supply. However, under drought stress and low phosphorus supply, S. superba
      seedlings allocated more photosynthetic products to their roots, and had higher
      phosphorus use efficiency, which could be an important physiological mechanism of
      the adaptation to drought stress and low phosphorus supply. Relative to the
      significant independent effects of provenance, watering level, and phosphorus
      supply, no significant interactive effects of the three factors were observed.

PMID- 20135992
TI  - [Seasonal changes of main water parameters of Reaumuria trigyna in different
      habitats].
AB  - By using press-volume technique, this paper studied the seasonal changes of water
      potential at saturated point (Psissat), water potential at turgor loss point
      (Psistlp), relative osmotic water content at turgor loss point (ROWCtlp),
      relative water content at turgor loss point (RWCtlp), relative content of
      apoplastic water (AWC), bound water/ free water (Va/Vo), and the difference
      between Psissat and (Psistlp(DeltaP) of Reaumuria trigyna growing on heavy
      solonchack, non-salinized soil, and saline soil. The seasonal changes of Psissat
      and Psistlp were in order of May > July > September, while those of AWC, Va/Vo,
      and DeltaP were in opposite sequence, indicating that the water deficit
      resistance ability of R. trigyna enhanced with season, being consistent with its
      growth rhythm. Comparing with other xerophytes, R. trigyna had very low Psissat
      and Psistlp, presenting its strong ability of maintaining high osmotic pressure
      and low water potential. Based on the water parameters measured in three months,
      and by using the subordination function of fuzzy mathematics, the water deficit
      resistance ability of R. trigyna was evaluated, which was the strongest on heavy
      solonchack, followed by on non-salinized soil, and on saline soil.

PMID- 20135993
TI  - [Water physiological characteristics of four perennial plant species around Cele
      Oasis in Xinjiang].
AB  - The water physiological characteristics of four perennial plant species (Populus
      euphratica, Tamarix ramosissima, Calligonum caput-medusae, and Alhagi
      sparsifolia) around Cele Oasis in Xinjiang were studied through their vegetation
      growth period. No signs of serious drought stress were observed in any of the
      test perennial species during their vegetation growth, and irrigation had little
      effects on the water status of the plants (P > 0.05). The seasonal variation
      characteristics of water physiological parameters differed with the plants. A.
      sparsifolia had the highest predawn water potential (PWP) and daily mean sap
      flow, but the lowest mean water use efficiency (WUE); C. caput-medusae had the
      highest mean WUE, and its PWP and sap flow were stable and had less seasonal
      change; T. ramosissima had the lowest PWP during its growth, and had better
      adaptation ability to the environment; and P. euphratica had relatively stable
      water physiological characteristics during its growth. The four perennial plant
      species had deep root systems to access underground water to satisfy their large
      demands for water, and thus, well adapted to the harsh environmental conditions
      around Cele Oasis.

PMID- 20135994
TI  - [Spatial-temporal variation of soil organic carbon and its relations to soil
      physical properties in degraded alpine grasslands].
AB  - By using grid sampling method, the spatial-temporal variation of soil organic
      carbon (SOC) and its relations to soil physical properties in degraded alpine
      grasslands in North Tibet were studied. The SOC content and its density both in
      surface (0-10 cm) and in subsurface (10-20 cm) layers decreased in order of
      slightly degraded grassland > normal grassland > moderately degraded grasslands >
      seriously degraded grasslands, and the differences of SOC content and its density
      between the two layers showed the same variation trend. An opposite trend was
      observed in the annual variation rates of SOC content and its density in
      different grasslands, and the variation was larger in surface than in subsurface
      layer. The annual accumulation rate of SOC in 0-10 cm layer in not degraded and
      slightly degraded grasslands was 0.018 and 0.003 g x kg(-1), being 6.0 and 2.0
      times of that in 10-20 cm layer, while the annual loss rate of SOC in 0-10 cm
      layer in moderately and seriously degraded grasslands was 0.150 and 0.231 g x kg(
      1), being 2.3 and 2.2 times of that in 10-20 cm layer, respectively. The total
      annual loss of SOC in moderately and seriously degraded grasslands was 3.8 times
      of the total annual accumulation of SOC in not degraded and slightly degraded
      grasslands. The degraded alpine grasslands in North Tibet had an average annual
      SOC loss of 7.87 x 10(7) t C x a(-1), and a greater potential to further loss in
      the future. The SOC content was significantly positively correlated with the
      contents of 5.0-1.0 mm, 1.0-0.5 mm, and 0.5-0.25 mm soil aggregates, soil bulk
      density, and soil moisture content.

PMID- 20135995
TI  - [Changes in plant communities and soil microbial physiological groups of
      artificial grasslands established for different years in headwater region of
      Yangtze River and Yellow River].
AB  - An investigation was made on the plant communities of artificial grasslands
      established for different years in headwater region of Yangtze River and Yellow
      River, and the related soil physical and chemical properties and soil microbial
      physiological groups were analyzed. With the increase of establishment years,
      most of plant communities on the grasslands showed a "V" type change trend in
      their quantities, i.e., high-low-high, but the forbs biomass had a "A" type
      change trend and the sedge biomass increased gradually. Soil nutrients presented
      a "V" type but soil bulk density presented a "A" type change trend, while soil pH
      presented a decreasing trend. Most of soil microbial physiological groups and
      microbial biomass carbon showed a "V" type change trend, phosphorus-dissolving
      bacteria showed a "A" type change trend, denitrifying bacteria decreased
      gradually, while cellulose-decomposing bacteria showed an increasing trend. The
      numbers of soil microbes had a close relationship with tested soil factors, and
      the soil microbial physiological groups were directly or indirectly affected by
      the soil factors. All the results indicated that the establishment of artificial
      grassland and the positive succession of vegetation could effectively improve
      soil physical and chemical properties, which benefit for the beneficial microbes
      to settle down and propagation, while proliferation of the non-beneficial
      microbes was inhibited.

PMID- 20135996
TI  - [Effects of tillage and mulching on orchard soil moisture content and temperature
      in Loess Plateau].
AB  - A field experiment was conducted to study the effects of different tillage system
      (no-tillage, rotary tillage, and plow tillage) and mulching (straw mulch, sod
      mulch, and film mulch) on the orchard soil moisture content and temperature in
      Loess Plateau. Under different tillage system, the soil moisture content in 0-1 m
      layer differed significantly in May, with the sequence of no-tillage (14.28%) >
      rotary tillage (14.13%) > plow tillage (13.57%), but had less difference in
      September. Straw mulch induced significantly higher soil moisture content than
      sod mulch, film mulch, and no-mulch. Among the treatments tillage plus mulching,
      no-tillage plus straw mulch resulted in the greatest soil water storage. The
      average soil temperature at daytime was in order of film mulch > no-mulch > sod
      mulch > straw mulch, and the change range of soil temperature was no-mulch > film
      mulch > sod mulch > straw mulch. Soil water storage under different mulching
      treatments was not always negatively correlated with soil temperature, but
      depended on the water conservation effect and heat-preserved capacity of mulching
      material. Above all, the main conservation tillage system for the orchards in
      Loess Plateau would be no tillage plus straw mulch.

PMID- 20135997
TI  - [Effects of irrigation with regenerated water on the growth and quality of
      alfalfa].
AB  - A pot experiment was conducted to study the effects of irrigation with
      regenerated water on the growth, nutrient uptake, and quality of alfalfa. Four
      treatments were installed, i.e., irrigation with fresh water (Q), irrigation with
      regenerated water (Z), mixed irrigation with regenerated water and fresh water (Z
      + Q), and rotational irrigation with regenerated water and fresh water (Z/Q).
      Comparing with treatment Q, treatment Z increased the stem length, lateral branch
      number, and plant biomass significantly, but decreased leaf area. Treatments Z, Z
      + Q, and Z/Q increased plant soluble protein content by 78.43%, 83.68% and
      72.53%, respectively, but treatment Z decreased plant soluble sugar content.
      Treatment Z increased plant Ca and Mg contents by 27.78% and 26.61%, and
      treatments Z and Z + Q decreased plant Fe content by 28.71% and 10.09%,
      respectively. Treatments Z, Z + Q, and Z/Q increased the cadmium content in above
      ground part of alfalfa by 98.6%, 89.5%, and 59.0%, respectively, but the cadmium
      and lead contents were still lower than the thresholds of National Sanitation
      Standard (GB 13078-2001). It was suggested that regenerated water could be used
      as a source of irrigation water in alfalfa growth, but its long-term effect
      should be concerned.

PMID- 20135998
TI  - [Effects of limited supplemental irrigation with catchment rainfall on potato
      growth in rainfed areas of western Loess Plateau].
AB  - Field experiments were conducted to study the effects of limited supplemental
      irrigation with catchment rainfall on the growth of potato cultivars Daxiyang and
      Tongshu 23 in rainfed areas of western Loess Plateau. Supplemental irrigation
      with catchment rainfall at seedling stage increased the potato yield
      significantly, and the increment was higher for Daxiyang than for Tongshu No. 23.
      Supplemental irrigation at tuber expanding stage increased the yield of Tongshu
      23, but decreased the yield of Daxiyang. Low amount of supplemental irrigation
      (45 mm) increased the water use efficiency (WUE) and irrigation water use
      efficiency (IWUE) of Tongshu 23. For Daxiyang, its WUE and IWUE were higher when
      the supplemental irrigation was made at seedling stage than at tuber expanding
      stage. Supplemental irrigation increased the tuber yield and the percentages of
      bigger and medium tubers of Tongshu 23, but the percentages of green and blet
      tubers were also increased. As for Daxiyang, supplemental irrigation increased
      the percentages of bigger and smaller tubers, as well as the percentage of blet
      tuber.

PMID- 20135999
TI  - [Effects of regulated deficit irrigation on water consumption characteristics and
      water use efficiency of winter wheat].
AB  - With the high-yielding winter wheat cultivar Jimai 22 as test material, a field
      experiment was conducted in Yanzhou of Shandong to examine the effects of
      regulated deficit irrigation on the water consumption and water use efficiency
      (WUE) of the cultivar. Five treatments were installed, i.e., the soil relative
      moisture content at sowing, jointing, and anthesis stages being 80%, 65% and 65%
      (W0), 80%, 70% and 70% (W1), 80%, 80% and 80% (W2), 90%, 80% and 80% (W3), and
      90%, 85% and 85% (W4), respectively. Under the condition of 228 mm precipitation
      in growth season, the total water consumption was higher in treatments W1 and W4
      than in treatments W0, W2, and W3, and no difference was observed between
      treatments W1 and W4. Comparing with W4, treatment W1 decreased the water storage
      in 0-200 cm soil layer and the water consumption by wheat from jointing to
      anthesis stages, but increased the water consumption from anthesis to maturity
      stages. The water consumption rates at the stages from jointing to anthesis and
      from anthesis to maturity in treatment W4 were higher. Under regulated deficit
      irrigation, treatment W0 had higher WUE, but the grain yield was the lowest. The
      WUE in other treatments increased first, and then decreased with increasing
      irrigation amount. Both the water consumption and the grain yield were the
      highest in treatments W1 and W4, and treatment W1 had higher irrigation water use
      efficiency and irrigation benefit than treatment W4, being the best irrigation
      regime of high-yielding and water-saving in our study.

PMID- 20136000
TI  - [Effects of controlled-release fertilizers on summer maize grain yield, field
      ammonia volatilization, and fertilizer nitrogen use efficiency].
AB  - A field experiment with colophony-coated fertilizer (CRF) and sulfur-coated
      fertilizer (SCF) showed that under the same application rates of N, P and K,
      applying CRF and SCF increased the summer maize grain yield by 13.15% and 14.15%,
      respectively, compared to the application of common compound fertilizer CCF. When
      the applied amount of CRF and SCF was decreased by 25%, the yield increment was
      9.69% and 10.04%, respectively; and when the applied amount of CRF and SCF was
      decreased by 50%, the yield had less difference with that under CCF application.
      The field ammonia volatilization rate in treatments CRF and SCF increased slowly,
      with a peak appeared 7 days later than that in treatment CCF, and the total
      amount of ammonia volatilization in treatments CRF and SCF was ranged from 0.78
      kg N x hm(-2) to 4.43 kg N x hm(-2), with a decrement of 51.34%-91.34% compared
      to that in treatment CCF. The fertilizer nitrogen use efficiency and agronomic
      nitrogen use efficiency of CRF and SCF were also significantly higher than those
      of CCF.

PMID- 20136001
TI  - [Alleviation effects of LaCl3 on photosynthetic characteristics of cucumber
      seedlings under nitrate stress].
AB  - By the method of hydroponic culture, this paper studied the alleviation effects
      of LaCl3 on the photosynthetic characteristics of cucumber seedlings under
      nitrate (140 mmol NO3(-) x L(-1)) stress, with the related mechanisms discussed.
      Under nitrate stress, the seedlings leaf chlorophyll and carotenoids contents
      decreased significantly, and the leaf Mg2+-ATPase, Ca2+-ATPase activities also
      decreased. On the 7th day of nitrate stress, the decrease of seedlings
      photosynthetic rate was mainly due to stomatal limitation; but on the 12th day of
      nitrate stress, the decrease was mainly due to no-stomatal limitation. Supplement
      with LaCl3 could make the cucumber seedlings keep relatively higher leaf Mg2+
      ATPase and Ca2+-ATPase activities and chlorophyll and carotenoids contents, and
      applying 20 micromol x L(-1) of LaCl3 could increase the carotenoids content
      significantly. LaCl3 could also improve the leaf gas exchange, and alleviate the
      decrease of leaf Fv/Fm, PhiPSII, AQY, CE, and qp under nitrate stress, which
      helped the leaves making good use of light energy and maintaining higher CO2
      assimilation capacity. An additional 20 micromol x L(-1) of LaCl3 could alleviate
      the nitrate stress on the photosynthesis of cucumber seedlings efficiently, but
      an additional 200 micromol x L(-1) of LaCl3 only had the alleviation effect at
      the initial period of nitrate stress. Our results could benefit to the
      improvement of greenhouse soil.

PMID- 20136002
TI  - [Effects of irrigation stage and amount on winter wheat fructan accumulation and
      translocation after anthesis and water use efficiency].
AB  - Field experiments were conducted in Tai' an and Yanzhou of Shandong Province in
      2004-2005 and 2005-2006 to study the effects of irrigation stage and amount on
      the accumulation and translocation of fructan in winter wheat penult stem and
      sheath after anthesis and the water use efficiency. No irrigation in whole growth
      period promoted the translocation of fructan from penult stem and sheath to grain
      at late grain-filling stage. Irrigation with 60 mm water at jointing and anthesis
      stages increased the flag leaf photosynthetic rate and photo-assimilate
      accumulation after anthesis, and the contribution of the photo-assimilates to the
      grain. Irrigation with 60 mm water at jointing, anthesis, and grain-filling
      stages, and with 90 mm water at jointing and anthesis stages decreased the flag
      leaf photosynthetic rate at late grain-filling stage, increased the photo
      assimilate accumulation before anthesis and the contribution of the photo
      assimilates to the grain, and reduced the translocation of the photo-assimilates
      after anthesis to the grain. Excessive irrigation also increased the contents of
      fructan with the degree of polymerization (DP) > or = 4 and = 3 in penult stem
      and sheath at late grain-filling stage, limiting the translocation of fructan
      from penult stem and sheath to grain. Irrigation with 60 mm water at jointing and
      anthesis stages led to a higher grain yield and the highest water use efficiency,
      while irrigation with 60 mm water at jointing, anthesis, and grain-filling
      stages, and with 90 mm water at jointing and anthesis stages had little effects
      on the grain yield but decreased the water use efficiency.

PMID- 20136003
TI  - [Effects of soil moisture regime on greenhouse tomato yield and its formation
      under drip irrigation].
AB  - Field plot experiment was conducted to study the effects of soil moisture regime
      at different growth stages on the fruit size, fruit number, percentage of
      malformed fruit, and yield formation of greenhouse tomato under drip irrigation,
      and the relationships between tomato yield and irrigation amount. Moderate soil
      water deficit (50%-55% of field capacity) at tomato's seedling stage increased
      the fruit number but reduced the fruit size, decreased the percentage of
      malformed fruit, and made the fruit maturation mainly concentrated in later
      picking period. Severe water deficit (less than 65% of field capacity) at
      flowering and fruit-developing stages promoted fruit maturation, but decreased
      fruit number and increased the formation of small and malformed fruits. The soil
      moisture content higher than 80% or lower than 65% of filed capacity at fruit
      maturation stage less affected fruit maturation but decreased fruit yield, and
      lower than 65% of filed capacity also decreased the fruit number and increased
      the percentage of malformed fruit. No significant effects of irrigation amount on
      fruit maturation were observed. The correlations of tomato yield and its water
      use efficiency with irrigation amount could be well described by quadratic
      function. The fruit number and total yield were higher while the percentage of
      malformed fruit was lower when the soil moisture content was controlled at 60%
      65% of field capacity at seedling stage, 70%-75% of field capacity at flowering
      stage, and 70%-75% of field capacity at fruit-developing stage, which could be
      used as the optimal soil moisture indices for the greenhouse tomato production
      under drip irrigation.

PMID- 20136004
TI  - [Shade-tolerance indices of maize: selection and evaluation].
AB  - A field experiment was conducted to study the morphological, physiological, and
      yield traits of 24 maize cultivars under 50% shading. Comparing with the control,
      50% shading decreased the plant height, stem diameter, leaf net photosynthetic
      rate (Pn), specific leaf weight (SLW), aboveground dry matter accumulation, ear
      length and diameter, axis diameter, and kernels per row. The interval from
      anthesis to silking (ASI) was prolonged, and the grain yield was decreased
      significantly. The percent changes of ASI, Pn, SLW, and kernels per row were
      significantly correlated with aboveground dry matter accumulation and grain
      yield, being able to be used as the indices to evaluate the maize shade-tolerance
      in field. Cluster analysis using comprehensive shade-tolerance traits as
      evaluation parameters indicated that 14 maize cultivars including Zhengdan 958,
      Xundan 20, and Denghai 602, etc. were of shade-tolerance type, and 10 cultivars
      (Anyu 12 and Yuyu 22, etc. ) were of shade-sensitive type. It was suggested that
      adopting the morphological, physiological and yield traits as the indices to
      evaluate the shade-tolerance of maize would be more objective, simple and
      practical.

PMID- 20136005
TI  - [Distribution characteristics of soil pH, CEC and organic matter in a small
      watershed of the Loess Plateau].
AB  - Soil chemical properties play important roles in soil ecological functioning. In
      this study, 207 surface soil (0-20 cm) samples were collected from different
      representative landscape units in a gully watershed of the Loess Plateau to
      examine the distribution characteristics of soil pH, cation exchange capacity
      (CEC) and organic matter, and their relations to land use type, landform, and
      soil type. The soil pH, CEC and organic matter content ranged from 7.7 to 8.6,
      11.9 to 28.7 cmol x kg(-1), and 3.0 to 27.9 g x kg(-1), and followed normal
      distribution, log-normal distribution, and negative binomial distribution,
      respectively. These three properties were significantly affected by land use
      type, landform, and soil type. Soil CEC and organic matter content were higher in
      forestland, grassland and farmland than in orchard land, and soil pH was lower in
      forestland than in other three land use types. Soil pH, CEC and organic matter
      content were higher in plateau land and sloping land than in gully bottom and
      terrace land. Soil CEC and organic matter content were higher in dark loessial
      soil and rebified soil, while soil pH was higher in yellow loessial soil. Across
      all the three landscape factors, soil CEC and organic matter content showed the
      similar distribution pattern, but an opposite distribution pattern was observed
      for soil pH.

PMID- 20136006
TI  - [Stream ecosystem health assessment based on the measurement of leaf litter
      breakdown: a case study in Hengshishui River of Guangdong Province].
AB  - Based on the Gessner' s model of leaf litter breakdown, the functional integrity
      and ecosystem health of Hengshishui River in Guangdong Province were assessed,
      and the breakdown rates of Castanopsis fissa and Schima superba leaf litters at
      the sites unpolluted and polluted by acid mine drainage were compared. The leaf
      litters of the two tree species had a significantly lower breakdown rate at
      polluted than at unpolluted sites (P < 0.05). According the Gessner's model, all
      polluted sites had an ecosystem health score 0, while all unpolluted sites had a
      score 2, indicating that the health status of polluted river reaches were
      severely damaged. The biological assessment of stream ecosystem health was
      consistent with the results of water quality analysis, indicating that the leaf
      litter breakdown model was a suitable index of stream status.

PMID- 20136007
TI  - [Agricultural eco-economic system coupling in Zhifanggou watershed in hilly-gully
      region of Loess Plateau].
AB  - Agricultural eco-economic system coupling is an organic unit formed by the
      inherent interaction between agricultural ecosystem and economic system, and
      regulated and controlled by mankind moderate interference. Its status can be
      expressed by the circular chain-net structure of agricultural resources and
      agricultural industry. The agricultural eco-economic system in Zhifanggou
      watershed has gone through the process of system coupling, system conflict,
      system coupling, and partial conflict in high leverage, which is caused by the
      farmers' requirement and the state's macro-policy, economic means, and
      administrative means. To cope with the problems of agricultural eco-economics
      system coupling in Zhifanggou watershed, the optimal coupling model should be
      established, with tree-grass resources and related industries as the core.

PMID- 20136008
TI  - [Ecological compensation criterion in Gannan Tibetan Autonomous Prefecture based
      on minimum-data method].
AB  - Quantitatively setting ecological compensation criterion is a focus and a
      difficulty in establishing ecological compensation mechanism. Based on the 1987
      2007 meteorological data and the 2007 social survey data of Gannan Tibetan
      Autonomous Region, the supply curves of grassland ecosystem services in the
      Region were simulated by the methods of minimum-data, social survey, and
      precipitation storage estimation. The opportunity cost of implementing ecological
      compensation in the Region in 2007 was 503.6 yuan x hm(-2), per unit water
      conservation volume supplied by grassland ecosystem was 1110.7 m3 x hm(-2), and
      ecological compensation criterion was 788.6 yuan x hm(-2). The total water
      conservation volume supplied by grassland ecosystem was 2.56 x 10(9) m3.

PMID- 20136009
TI  - [Extraction of structured vegetation cover index for Loess Area in North Shaanxi
      based on TM images].
AB  - Based on the concept of structured vegetation cover index (Cs) and by using TM
      images as the information source, the extraction way of Cs for Loess Area in
      North Shaanxi by using remote sensing techniques was explored. In study area, Cs
      was better than the traditional projected vegetation coverage index in expressing
      the relationships between vegetation structure and soil erosion. The Cs was
      closely related to the remote sensing vegetation indices, such as green indices
      NDVI (Normalized Difference Vegetation Index) and MSAVI (Modified Soil Adjusted
      Vegetation Index), and yellow indices NDSVI (Difference Senescent Vegetation
      Index) and NDTI (Normalized Difference Tillage Index). The combination of the
      green and yellow indices could better express the effects of vegetation on soil
      erosion, compared with the single index. Among these remote sensing vegetation
      indices, the MSAVI and NDTI could be the ideal green and yellow vegetation
      indices for the extraction of Cs from TM images. It was possible to extract the
      Cs from remote sensing data through the regression analysis of Cs and remote
      sensing vegetation indices. However, this method was just validated and applied
      to the study area. Whether it could be applied to other regions was needed to be
      further validated due to the phonological differences from one region to another.

PMID- 20136010
TI  - [Spatiotemporal characteristics of MODIS NDVI in Hulunber Grassland].
AB  - Time-series MODIS NDVI datasets from 2000 to 2008 were used to study the spatial
      change trend, fluctuation degree, and occurrence time of the annual NDVImax of
      four typical grassland types, i.e., lowland meadow, temperate steppe, temperate
      meadow steppe, and upland meadow, in Hulunber Grassland. In 2000-2008, the
      vegetation in Hulunber Grassland presented an obvious deterioration trend. The
      mean annual NDVImax of the four grassland types had a great fluctuation,
      especially in temperate steppe where the maximum change in the mean value of
      annual NDVImax approximated to 50%. As for the area change of different grade
      grasslands, the areas with NDVImax between 0.4 and 1 accounted for about 91% of
      the total grassland area, which suggested the good vegetation coverage in the
      Grassland. However, though the areas with NDVImax values in (0.4, 0.8) showed an
      increasing trend, the areas with NDVImax values in (0.2, 0.4) and (0.8, 1)
      decreased greatly in the study period. Overall, the deteriorating grassland took
      up about 66.25% of the total area, and the restoring grassland took the rest.
      There was about 62.85% of the grassland whose NDVImax occurred between the 193rd
      day and the 225th day in each year, indicating that this period was the most
      important vegetation growth season in Hulunber Grassland.

PMID- 20136011
TI  - [Effects of topographic correction on remote sensing estimation of forest
      biomass].
AB  - Based on four commonly used models (Cosine model, C model, C + SCS model, and
      Minnaert model), the topographic effects in Landsat-5 image of Maoershan region
      in Heilongjiang Province acquired on July 21, 2007 were calibrated on the
      platform of IDL language. The 4 models were validated from the aspects of visual
      differences and quantitative statistical features of the images. After the
      correlation analysis on the corrected remote sensing data and the forest biomass
      data, the biomass retrieving models were constructed. Furthermore, the effects of
      different topographic factors on the estimation of forest biomass were studied.
      The results showed that due to its liner presumption, the topographic correction
      combined with K-T transformation was not suitable for forest biomass estimation,
      and the correlations between the remote sensing data and the forest biomass
      fluctuated significantly. The parameters of the transformation needed to be
      adjusted in accordance with the information of land surface. The information
      content of vegetation index was significantly increased after topographic
      correction, and the correlation between vegetation index and forest biomass was
      enhanced greatly. Among the four models, Cosine model over-corrected the shaded
      areas in image, C model and C + SCS model had good correction performance by
      using semi-empirical parameters, while Minnaert model decreased the error of
      biomass estimation and improved the precision of remote sensing retrieving models
      effectively.

PMID- 20136012
TI  - [Effects of water temperature and feeding on respiratory metabolism of juvenile
      Salvelinus fontinalus].
AB  - The oxygen consumption and ammonia excretion rates of juvenile brook trout
      (Salvelinus fontinalus) under satiation and starvation were measured at different
      levels of water temperature [(5.5 +/- 0.5), (8.5 +/- 0.5), (11.5 +/- 0.5), (14.5
      +/- 0.5), (17.5 +/- 0.5) degrees C], aimed to study the effects of water
      temperature and feeding on the respiratory metabolism of the fish. Under
      satiation, the oxygen consumption and ammonia excretion rates of juvenile S.
      fontinalus at the five temperature levels increased rapidly to the maximum, and
      then decreased gradually to the initial state. The regression equations of oxygen
      consumption rate (OR) and ammonia excretion rate (NR) to water temperature (t)
      were OR = -0.0601 t4 + 2.5542 t3 - 39.256 t2 + 276.26 t - 598.75 (R2 = 1, 4.5
      degrees C < t < 17.5 degrees C) and NR = - 0.0020 t4 + 0.0826 t3 - 1.2318 t2 +
      8.6186 t - 18.838 (R2 = 1, 4.5 degrees C < t < 17.5 degrees C), respectively.
      Under starvation, the regression equations were OR = 13.723 t(0.9738) (R2 =
      0.9974, 4.5 degrees C < t < 17.5 degrees C) and NR = 0.1687 t(1.0896) (R2 =
      0.9977, 4.5 degrees C < t < 17.5 degrees C), respectively. The optimal
      temperature range was 11.5 degrees C-14.5 degrees C. The juvenile S. fontinalus
      in starvation was heavily depended on fat and carbohydrates.

PMID- 20136013
TI  - [Super-cooling ability and its relations to body's water and fat contents of
      overwintering Hyphantrian cunea (Lepidoptera: Arcidae) pupae].
AB  - The determinations of super-cooling ability and body' s water and fat contents of
      overwintering Hyphantria cunea pupae showed that during overwintering, the female
      and male H. cunea pupae had the similar change patterns in their cold-resistance
      ability, i.e., increased with decreasing air temperature, but their body's water
      and fat contents, super-cooling point (SCP), and freezing point (FP) differed at
      different overwintering stages. The SCP was significantly lower at pre- and mid
      overwintering stages than at late-overwintering stage, while FP had less
      difference among the stages. The body's water content was significantly higher at
      mid-overwintering stage than at pre- and late-overwintering stages. Comparing
      with non-overwintering pupae, the overwintering pupae had significantly lower SCP
      and FP, but significantly higher body's water and total fat contents. Regression
      analysis showed that there was a negative relationship between the water content
      and the SCP of female and male pupae (P < 0.05).

PMID- 20136014
TI  - [Calling and mating behaviors of adult Orthaga achatina (Lepidoptera:
      Pyralidae)].
AB  - A laboratory study was made on the calling and mating behaviors of adult Orthaga
      achatina at (27 +/- 1) degrees C, (60 +/- 10)% RH, and 14 L: 10 D photoperiod.
      The female O. achatina did not call until the start of scotophase, with the
      calling percentage increased sharply at the 5th hour and reached the peak at the
      6th-7th hour of scotophase. The calling percentage varied with moth age, being
      the highest (> 70%) at the age of 2-3 d. The mating behavior could be divided
      into two successive periods, i.e., calling period and mating period. The mating
      between female and male O. achatina occurred during the 5th-9th hour of
      scotophase, with the peak at the 6th-7th hour into scotophase, which was in
      accordance with the peak time of female calling behavior. Females mated only one
      time during their whole life. Treatment 1 female : 2 male showed a significantly
      higher mating percentage, but a significantly shorter mating duration time,
      compared with treatment 1 female : 1 male.

PMID- 20136015
TI  - [Bt toxic protein expression in insect-resistant transgenic corns and its
      transfer to and accumulation in Ostrinia furnacalis].
AB  - Taking the insect-resistant transgenic corn varieties G03-2396 and G03-2739 and
      the conventional corn variety Suyu 16 as test materials, a bioassay in laboratory
      was conducted to test their resistance against Ostrinia furnacalis. The Bt toxin
      expression in different tissues of the two transgenic corns, the ingestion of Bt
      toxin by the 3rd and 5th instar of O. furnacalis, and the Bt toxin amount in
      feces of O. furnacalis larvae fed with Bt corns were analyzed by using enzyme
      linked-immunosorbent-assay (ELISA). It was found that the central leaves of both
      G03-2396 and G03-2739 had great toxicity to O. furnacalis larvae. After fed with
      the central leaves for 6 d, the survival rate of neonate larvae was less than 3%,
      and that of the 3rd instar larvae was less than 70%. Female ears had smaller
      toxicity than central leaves. The Bt toxic protein was detected both in the
      leaves and in the female ears of the two transgenic corns, but its content was
      higher in central leaves than in female ears. The Bt toxic protein expression
      level was in order of G03-2739 central leaf (39.6 microg x g(-1) FM) > G03-2396
      central leaf (26.1 microg x g(-1) FM) > G03-2396 female ear (17.0 microg x g(-1)
      FM) > G03-2739 female ear (14.6 microg x g(-1) FM). When fed with central leaf or
      female ear, the Bt toxic protein amount in the 3rd instar larvae was
      significantly higher than that in the 5th instar larvae. For the same age instar
      larvae, the Bt toxic protein content was significantly higher after fed with
      central leaf than fed with female ear, so did the Bt toxic protein content in
      larvae feces, being the highest (10.4 microg x g(-1) FM) for the 5th instar
      larvae fed with G03-2739 central leaf, and the lowest (2.7 microg x g(-1) FM) for
      the 3rd instar larvae fed with G03-2739 female ear.

PMID- 20136016
TI  - [Antimicrobial activity of volatile oil from Atractylodes lancea against three
      species of endophytic fungi and seven species of exogenous fungi].
AB  - In order to investigate the inhibitory effects of host plants secondary
      metabolites on the growth of endophytic and exogenous fungi, the volatile oil
      from medicinal plant Atractylodes lancea was extracted with organic solvent
      extraction method, and its antimicrobial activity against three species of
      endophytic and seven species of exogenous fungi was determined by paper disc
      assay and spread-plate. The volatile oil had inhibitory effects on the growth of
      test endophytic fungi. It had strong antimicrobial activity against Rhodotorula
      glutinis and Saprolegnia, but weak activity against Rhizopus and Absidia. It
      suppressed the sporulation of Trichoderma viride and Aspergillus niger, but no
      effects on the growth of Phytophthora. Under the stress of high concentration
      volatile oil, the hyphal branches of test endophytic fungi increased, the
      distance between the branches became shorter, and the growth of aerial hyphae was
      inhibited. The test endophytic fungi had remarkable ability to metabolize and
      transform the volatile oil, and decreased the contents of its main ingredients.
      All the results showed that the volatile oil extracted from A. lancea had
      inhibitory effects on the growth of endophytic fungi, but the fungi could adapt
      to the volatile oil via metabolizing and decomposing it.

PMID- 20136017
TI  - [Relationships between temperature change and microbial amount in inactive ice
      wedges in Yitulihe, Northeast China].
AB  - Ice-wedge is an indicator of paleoclimate change. The delta18 O concentration in
      different layers could reflect the change of paleotemperature during ice-wedge
      growth. In the late 1980s, inactive ice wedges were found in Yitulihe, Northeast
      China, which were the south-most ones so far and were important in climatic and
      environmental research. In this paper, the delta18 O concentration and microbial
      number in the inactive ice-wedges were analyzed by using stable isotope,
      fluorescence microscopy counting, and flow cytometer (FCM). During the ice-wedge
      growth in Yitulihe area, there were three short-term paleotemperature
      fluctuation, and three times of fluctuation in microbial amount in different ice
      wedge layer. Correlation analysis indicated that there was a converging
      relationship between the temperature change and microbial amount in the ice
      wedges. The lower the temperature when ice-wedge layer formed, the less the
      microbes survived in the layer.

PMID- 20136018
TI  - [Effects of pig manure and oxytetracycline on microbial number and activity in
      soils with different fertility levels].
AB  - An incubation test was conducted to study the effects of antibiotics
      oxytetracycline on the microbial number and activity in three soils varied with
      fertility level under the conditions with or without pig manure application. The
      soils were injected with six concentrations (0, 0.1, 1, 10, 100, and 1000 mg x
      kg(-1)) oxytetracycline, and incubated for 30 d at 25 degrees C. Soil samples
      were collected on the 1st, 4th, and 30th day of incubation to measure the
      bacterial number, respiratory activity, and enzyme activity. Under no pig manure
      application, oxytetracycline had little effects on the soil bacterial number and
      activity. The EC10 values of oxytetracycline based on a 10% decrement of
      bacterial number, respiratory activity, enzyme activity, and NO3(-)-N
      concentration in treatment without pig manure were 36-1000 mg x kg(-1), 20-1000
      mg x kg(-1), and 4-1000 mg x kg(-1) for S1, S2 and S3, while those in treatment
      with pig manure application were 2-656 mg x kg(-1), 2-81 mg x kg(-1), and 1-42 mg
      x kg(-1) for S1, S2 and S3, respectively. Soil fertility level had obvious
      effects on the dose-response relations between oxytetracycline and soil microbial
      number and activity. The effects of oxytetracycline on soil microbial number and
      activity increased with increasing soil fertility level, and the effects on
      microbial number and respiratory activity were higher than those on enzyme
      activity and NO3(-)-N concentration. The effects of oxytetracycline on soil
      microbial number and activity were time-depending, being the greatest on the 4th
      day of incubation. Overall speaking, oxytetracycline could exert temporary
      inhibition on soil microbes.

PMID- 20136019
TI  - [Spatiotemporal distribution of total nitrogen and total phosphorus in sediments
      of Xiangxi Bay, Three Gorges Reservoir].
AB  - The spatiotemporal distribution of total nitrogen (TN) and total phosphorus (TP)
      in sediments of Xiangxi Bay, Three Gorges Reservoir was investigated from October
      2004 to July 2006, with related affecting factors analyzed. The TN and TP
      concentrations in the sediments were higher in the middle stretch but lower in
      the two edges of the Bay. The maximum value of TN concentration (1.08 mg x g(-1))
      appeared in the middle part of the Bay, and the minimum (0.89 mg x g(-1))
      occurred at the adjacent areas to the river mouth; while the maximum value of TP
      concentration (1.07 mg x g(-1)) appeared in the middle, and the minimum (0.80 mg
      x g(-1)) was in the edges of the Bay. The TN concentration decreased in the
      sequence of autumn-winter-spring, but increased from spring to summer
      dramatically; while the seasonal variation of TP concentration was not very
      significant, with the maximum occurred in spring. Significant inter-annual
      variations were observed in the TN and TP concentrations. The spatial
      distributions of TN and TP concentrations were mainly affected by the
      sedimentation of suspended matter. In the regions where sedimentation rate was
      high, the TN and TP concentrations were also very high. The seasonal fluctuation
      of TN concentration was mainly affected by river discharge, while that of TP
      concentration was mainly affected by point source pollution.

PMID- 20136020
TI  - [Effects of heavy metals pollution on paddy soil aggregates composition and heavy
      metals distribution].
AB  - Topsoil samples were collected from a polluted and an adjacent non-polluted paddy
      field in the Taihu Lake region of China. Different particle size fractions of
      soil aggregates were separated by low-energy dispersion procedure, and their mass
      composition and Pb, Cd, Hg, and As concentrations were determined. Under heavy
      metals pollution, the mass composition of sand-sized fractions reduced, while
      that of clay-sized fractions increased. The concentrations of test metals in
      different particle size fractions differed, with the highest in < 0.002 mm
      fraction, followed by in 2-0.2 mm fraction. In 0.02-0.002 mm and 0.2-0.02 mm
      fractions, all the test metals were relatively deficient, with an enrichment
      index of 0.56-0.96. The present study showed that the aggregation of fine
      particles could be depressed by heavy metals pollution, which in turn, led to a
      relative increase in the mass composition of fine particles and the associated
      allocation of heavy metals in weakly aggregated silt particles, and further,
      increased the risks of heavy metals translocation from polluted farmland into
      water and atmosphere. Further studies should be made on the impacts of heavy
      metals pollution on soil biophysical and biochemical processes and related
      mechanisms.

PMID- 20136021
TI  - [Early-warning and prediction technology of harmful algal bloom: a review].
AB  - Harmful algal bloom (HAB) occurs frequently and causes serious damage. To study
      the early-warning and prediction technology of HAB is of significance for the
      early-warning and prediction, ecological control, and disaster prevention and
      mitigation of HAB. This paper reviewed the research progress in the early-warning
      and prediction technologies of HAB, including transport prediction, specific
      factors critical value prediction, data-driven model, and ecological math model,
      and evaluated the advantages and disadvantages of these four types of
      technologies. Some new ideas were brought forward about the prediction of
      cyanobacterial growth rate based on cell characteristics, and the early-warning
      of cyanobacterial bloom based on algal community characteristics.

PMID- 20136022
TI  - [Periphyton and its application in water purification].
AB  - Periphyton widely exists in natural water bodies, with the characteristics of
      huge biomass generation, strong ecological function, and sensitive response to
      water quality. It removes the pollutants in water bodies mainly through the
      processes of absorption, metabolism, adsorption, and complexation, etc. Owing to
      its high tolerance against pollution and high removal efficiency for nitrogen and
      phosphorus, as well as the feasibility of recycling its cells at low cost,
      periphyton is a promising candidate for developing the treatment techniques of
      water purification. The newly-developed artificial periphyton systems, e.g.,
      algal turf scrubbers, periphyton biofilm systems, periphyton aquaculture systems,
      have been successfully applied in treating livestock manure, aquaculture
      wastewater, and municipal sewage. However, further researches are needed to
      understand the growth patterns of periphyton, its physiological responses to
      pollutants concentration, and its molecular biological mechanisms in removing
      pollutants.

PMID- 20136023
TI  - [Research advances in the responses of carbohydrates in grassland plants to
      environmental stress].
AB  - Carbohydrates are the main energy materials for plant metabolic activities.
      Enough carbohydrates stored in roots are necessary for plant re-growth, its
      tolerance against environmental stress, and the maintenance of grassland
      ecosystem stability. This paper summarized the influences of grazing, nitrogen
      fertilization, salt stress, drought, low temperature, and low oxygen stress on
      the carbohydrates in grassland plants, and introduced the advanced methods of
      measuring root carbohydrates. It was suggested that the research emphasis in the
      future should be paid on the relationships between root soluble sugar components
      and root physio-ecological functions.

PMID- 20136024
TI  - [Topsoil application in vegetation restoration in Japan].
AB  - Soil seed bank has the unique regional species composition and genetic
      characteristics, and plays important roles in maintaining species diversity and
      population density. Topsoil, as a kind of revegetation materials, has the
      potential in vegetation restoration. Based on the Japanese literatures, this
      paper introduced the characteristics and contents of revegetation with topsoil,
      and discussed the revegetation modes from the aspects of topsoil mixing ratio,
      slope surface condition, and topsoil collection depth. The application cases of
      topsoil in various habitat types such as forests, roads, wetlands, and abandoned
      lands were also introduced. Some suggestions to the further researches on topsoil
      application in vegetation restoration were proposed, e.g., to strengthen the
      practical research of topsoil, to determine the appropriate techniques and
      targets of topsoil application as well as the survey methods and applicability
      standards, and to develop the low cost and high-efficient new application ways of
      topsoil.

PMID- 20136025
TI  - Provide a health service that meets the needs of the population.

PMID- 20136026
TI  - Insurance literacy in the United States.
AB  - Health insurance reform in the United States can be traced back to former
      President Theodore Roosevelt in 1912 who called for universal health coverage.
      Since that time, various U.S. Presidents attempted to intervene to cover all
      Americans with some form of compulsory insurance. The election of President
      Barack Obama in 2008 was believed to be a beginning of a new dialog to transform
      health care in the United States by redesigning the insurance system in the
      country. The issue of insurance literacy and the need to educate citizens on
      insurance terminology are the focus of this article.

PMID- 20136027
TI  - "Migrant-friendly hospitals": a European initiative in an age of increasing
      mobility.
AB  - European cities are characterized by increasing numbers of foreign-born and
      foreign-language speaking inhabitants. The resulting cultural and linguistic
      diversity presents a number of challenges to health-care services. This paper
      describes a European initiative aimed at improving hospitals' responses to the
      health-care needs of migrants and ethnic minorities. We summarise the current
      health situation of these groups, describe how the EU initiative began and how it
      led to the Amsterdam declaration, and conclude by outlining current developments.

PMID- 20136028
TI  - The misuse of clinical paths as an instrument for funding inpatient care in
      Bulgaria.
AB  - Clinical paths in Bulgaria are used not as a method for quality assessment, but
      as an instrument to fund hospitals. Their use and incompleteness cause limited
      access of all Bulgarian citizens to the international treatment guidelines. That
      way quality of treatment worsens and mortality increases. The Bulgarian system of
      regulated medical guidelines by all therapeutic and surgical lines still suffers
      many deficiencies. The National Health Insurance Fund should use the system of
      clinical paths for quality control as well.

PMID- 20136029
TI  - Breaking down hospital costs for selected medical conditions in Canada.
AB  - Understanding the components of hospital costs is an important policy tool for
      analyzing total hospital spending or for budget planning. The objective of this
      study is to estimate the average cost per stay and number of stays for male and
      female acute care inpatients for the 15 most expensive medical conditions, and to
      determine whether there is a gender difference in the share of cost due to co
      morbidities. Regression analysis is used to account for gender and complexity, a
      proxy for co-morbidities. Our findings suggest on average male inpatient costs
      9.7% more to treat than a female inpatient.

PMID- 20136030
TI  - Influence of social support, depression, and self-esteem on burden of care among
      caregivers of oncology patients.
AB  - This study investigated the influence of social support, depression and self
      esteem on the burden of care among informal caregivers of oncology patients. The
      cross-sectional correlational study included 278 informal oncology caregivers.
      Results showed a significant main effect of self-esteem (F(1277) = 5.35, p <
      .05), and interaction effect of social support and depression (F(1277) = 4.86; p
      < 05) on caregivers' burden. Caregivers with high levels of depression (t = 4.06,
      df = 282, p < .001), and others with high levels of social support (t = 4.06, df
      = 282, p < .001) recorded significantly higher levels of caregivers' burden. This
      suggests the need for improving the psychological well-being of informal
      caregivers of oncology patients in the expanding role of family and community
      members in caring for cancer patients.

PMID- 20136031
TI  - Implementation of a diabetic foot management best practice guideline (BPG) in
      hemodialysis units.
AB  - The aim ofthis study was to examine the impact of introducing the Registered
      Nurses' Association of Ontario Best Practice Guideline (BPG), Assessment and
      management of foot ulcers for people with diabetes (2005), on foot ulcer
      incidence, recurrence, and amputation rate in adult diabetic clients who are
      undergoing chronic hemodialysis treatments. Fifty-seven individuals from three
      hemodialysis units participated in the study. Data were collected at three points
      in time over a 15-month period. A significant reduction in the number of wounds
      was noted (p < 0.05) from time one to time three, and the grade of wounds (p <
      0.01). However, five new amputations were reported Although implementation of the
      BPG showed a positive patient outcome, further research needs to be conducted
      with a larger sample size.

PMID- 20136032
TI  - Sodium thiosulfate, bisphosphonates, and cinacalcet for calciphylaxis.

PMID- 20136033
TI  - A descriptive study of the cultural competence of hemodialysis nurses.
AB  - Within a society that is becoming increasingly multicultural, it is vital for
      nurses to become culturally competent in order to meet the needs of a culturally
      diverse population. Cultural knowledge plays a primary role in influencing the
      quality of care that nurses provide on a daily basis. The purpose of this
      descriptive study was to assess the cultural competence level of hemodialysis
      nurses. The study was conducted in an outpatient setting at a large teaching
      hospital in Canada. The Inventory for Assessing the Process of Cultural
      Competence-Revised (IAPCC-R) was used as the questionnaire for this study. A
      convenience sample of 58 hemodialysis nurses completed the IAPCC-R tool. Data
      were analyzed using descriptive statistics. The nurses had a mean score of 65.58%
      on the IAPCC-R tool, indicating that they were culturally aware, but not
      culturally proficient. Further analysis of the IAPCC-R results showed that the
      nurses were lacking information in the area of cultural knowledge, but that they
      were motivated to become culturally competent. The findings from this study
      indicated that, in a society that is becoming increasingly multicultural,
      hemodialysis nurses were motivated to become culturally competent. There is a
      need for nurse educators to support nurses to reach this goal.

PMID- 20136034
TI  - False elevations in blood glucose readings with use of icodextrin (extraneal)
      peritoneal dialysis solution.

PMID- 20136035
TI  - [Exploratory eye movement as an endophenotype for schizophrenia].

PMID- 20136036
TI  - [Case report of anti-NMDA receptor encephalitis suspected of schizophrenia].
AB  - Recently, paraneoplastic encephalitis associated with ovarian teratoma, which
      predomi nantly affects young women, has been reported. Its symptoms are severe
      but often treatment-responsive and reversible. Various psychiatric symptoms
      occurring shortly after onset are characteristic of this encephalitis. A 22-year
      old female who had a fever and common cold-like symptoms presented with short
      term memory loss. She was suspected to have viral encephalitis, but the
      cerebrospinal fluid (CSF) showed no marked change. Shortly after that, she
      developed delusions and hallucinations and presented with psychomotor excitement.
      She was suspected of having schizophrenia and admitted to the psychiatry
      department. However, several days after admission, she showed upper limb
      convulsion, orofacial dyskinesias, and central hypoventilation and became
      unresponsive. The results of laboratory tests were within the normal range, and
      there was no marked elevation of anti-viral antibody titers. Brain imaging was
      normal, but a solid tumor containing soft tissue and calcified components,
      probably an ovarian teratoma, was discovered on an abdominal CT scan. Anti-N
      methyl-D-aspartate (NMDA) receptor antibody was positive in her CSF and blood
      serum, and we diagnosed her with "Anti-NMDA receptor encephalitis". Gamma
      globulin was very effective, and the ovarian teratoma was removed. Finally, she
      could be discharged from our hospital without any sequela, and returned to her
      job. Psychiatrists often encounter encephalitis patients with psychiatric
      symptoms. If the type of encephalitis is unknown, we should keep this disease in
      mind.

PMID- 20136037
TI  - [Burden on designated hospitals when they receive inpatients from distant places
      in accordance with the Medical Treatment and Supervision Act].
AB  - OBJECTIVE: The current Medical Treatment and Supervision Act places a burden on
      designated psychiafric hospitals with forensic wards. We aimed to clarify the
      rate of discharge beyond the jurisdictional catchment area, for which overnight
      training becomes quite cost-ineffective, as hospital staff must accompany the
      patients home. SUBJECTS: On September 30, 2008, there were 16 designated
      hospitals in Japan, and 447 inpatients in these hospitals. They were the subjects
      of this study. METHOD: We collected information on the 447 subjects regarding the
      postdischarge administrative division, the nearest railway station to the
      postdischarge residential location, "treatment stage", "overnight training" at
      the postdischarge residential location, and trouble during "overnight training".
      We analyzed the collected data using the "designated bed sufficiency ratio". We
      divided the 447 subjects into three groups: (1) Home inpatient group (home
      group); the administrative division of his/her postdischarge residential area is
      the same administrative division as the designated hospital. (2) Inpatient within
      a jurisdiction group (within group) ; the administrative division of his/her
      postdischarge residential area is not the same as the designated hospital but is
      in any administrative division within a jurisdiction of the Japanese Regional
      Bureau of Health and Welfare. (3) Inpatient outside a jurisdiction group (outside
      group) ; the administrative division of his/her postdischarge residential area is
      not the same as the designated hospital but is any administrative division
      outside a jurisdiction of the Japanese Regional Bureau of Health and Welfare. We
      compared: (1) the time required to travel to the railway station nearest the
      postdischarge residential location (time required), (2) traveling expenses, and
      (3) the distance from the railway station nearest the designated hospital to that
      of the postdischarge residential location (distance) between the three groups. We
      also analyzed staff comments regarding "overnight training". RESULTS: The lack of
      designated beds was a serious problem in two jurisdictions of Kinki and the
      Hokkaido Regional Bureau of Health and Welfare, with a "designated bed sufficient
      ratio" of 0.08 and 0.00, respectively. Twenty-four Japanese administrative
      divisions had no designated beds, while 37 administrative divisions had less than
      10 inpatients at the time of the survey. The numbers of people in the "home
      group", "within group", and "outside group" were 125 (28.0%), 166 (37.1%), and
      145 (32.4%), respectively. The "time required", traveling expenses, and distance
      were 1: 00, Yen 735, and 29.8 km in the "home group", 2: 51, Yen 5,764, and 165.3
      km in the "within group", and 4: 14, Yen 20,565, and 694.6 km in the "outside
      group". Seventy-nine (59.4%) of 133 subjects who were at the "return to community
      stage" had already experienced "overnight training". No difference was found in
      the rate of "overnight training" between the "home group", "within group", and
      "outside group". Staff comments included difficulties in providing staff for
      "overnight training", responsibilities during "overnight training", and
      difficulties in finding places of residence in the inpatients' hometowns.
      DISCUSSION: Because of the lack and maldistribution of designated beds in Japan,
      many patients are reluctantly admitted to designated hospitals far from their
      postdischarge residential areas, burdening not only hospital staff but also
      families and the inpatients themselves. Increasing the number of designated beds
      will solve this problem. An effective way would be to set up a ward with a small
      scale designated unit (less than 15 beds) in the 24 administrative divisions
      where there are no designaed beds at present.

PMID- 20136038
TI  - Fine particles (PM2.5) in ambient air of Lucknow city due to fireworks on Diwali
      festival.
AB  - People burn crackers world over on different occasions in different countries to
      express their happiness. Fireworks in large amounts aggravate the level of air
      pollutants and cause significant short-term air quality degradation with possible
      impact on human health. Fine particles (PM2.5 < or = 2.5 microm), which may pose
      detrimental effects on human health and ecosystems were monitored in a
      residential area of Lucknow city to assess the elevated level due to bursting of
      firecrackers during Diwali festival. The 24 hr mean PM2.5 of normal day, pre
      Diwali day, Diwali day and post Diwali day was found to be 124, 154, 352 and 174
      microg m(-3) respectively and much above the US-EPA limit (65 microg m(-3)). The
      12 hr mean concentration of PM2.5 on Diwali night (591 microg m(-3)) increased
      3.9 fold than the respective night of normal day (159 microg m(-3)) and was
      significantly higher (p<0.01) than normal day and pre and post Diwali night. Mean
      comparison showed that Diwali day was significantly (p<0.01) different from
      others (except post Diwali day) and for this high accumulation during night time,
      after fireworks (suspension) was found to be more responsible than the period of
      lighting of crackers (formation). This study indicated that there is high
      accumulation of PM2.5 generated due to fireworks on Diwali festival which remains
      suspended in the air for up to 20 hr During this period, extra mass burden of 289
      microg m(-3) equivalent to 1.9 normal day (of this study) was imposed in the
      environment. The short-term high accumulation of PM2.5 is a matter of serious
      concern for city dwellers as it can penetrate deep into the lungs and cause many
      respiratory and cardiovascular diseases.

PMID- 20136039
TI  - Testosterone and estradiol-17 beta dependent phospholipid biosynthesis in
      ovariectomized catfish, Heteropneustes fossilis (Bloch).
AB  - Effect of cumulative doses (7, 14 and 28 mg kg(-1) body weight) of testosterone
      (T) and estradiol-17 beta (E2) on total phospholipids (TP), phosphatidylcholine
      (PC), phosphatidylserine (PS), phosphatidylinositol (PI) and
      phosphatidylethanolamine (PE) in tissues were investigated during the gonadal
      recrudescence, in prespawning phase of the annual reproductive cycle in intact
      and ovariectomized freshwater catfish, Heteropneustes fossilis. After
      ovariectomy, the hepatic levels of TP and PE were elevated and remained
      unaffected for PC, PS and PE when compared with control. In general, T and E2
      were stimulatory fora specific class ofphospholipid in tissues of intact and
      ovariectomized catfish. These effects were higher at 14 and 28 mg kg(-1) body
      weight in ovariectomized catfish whereas 7 mg kg(-1) body weight of T and E2 have
      pronounced effect in intact ovaries. In conclusion, the various phospholipid
      biosynthesis were under T and E2 dependent. Among the phospholipid, the PC was
      the main constituent and was sex steroid dependent biosynthesis during
      prespawning phase.

PMID- 20136040
TI  - Studies on sorption properties of pathogens on natural materials.
AB  - Presence of pathogens in high numbers in waste water is a cause of concern.
      Techno economic feasibility has restricted the conventional and non conventional
      treatment approaches for pathogen removal. Despite prolific use, carbon
      adsorption technology remains an expensive treatment process. The present study
      investigates the use of rice husk (RH), saw dust (SD), groundnut shells (GS) as
      natural agro-residues and partially weathered deccan trap basalt (PWDTB) for
      their sorption capacities and desorption pattern for two indicator organisms viz.
      Escherichia coli K12 and Staphylococcus aureus. Sorption experiments were carried
      out at flow-rate of 1.5 bed volumes per hour (bv hr(-1)) forcell suspension
      volume of 4, 8, 16 and 32 bed volumes. PWDTB have shown high sorption coefficient
      and log removal for E. coli K12 whereas GS have shown high sorption coefficient
      and log removal for S. aureus. PWDTB have shown maximum desorption constant and
      log retention for E. coli K12 whereas GS have shown maximum desorption constant
      and log retention for S. aureus during desorption experiment. Retention pattern
      suggest that adsorption is partially irreversible for almost all the materials
      used. It suggest that PWDTB in combination with RH and / GS could help in removal
      of pathogens from waste water.

PMID- 20136041
TI  - Marine mycoflora in backwater ecosystem of Kerala, India.
AB  - Back water system of Kerala is well known for its fertility. Fungi play a vital
      role in detritus decomposition, nutrient cycling and energy flow in marine food
      web including backwater ecosystem. Present investigation on the diversity of
      marine fungi from two back waters of Kerala resulted in the isolation of 20
      marine fungi. These include 11 Ascomycetes, 1 Basidiomycete and 8 Mitosporic
      fungi. In terms of percent frequency of occurrence the most common species
      obtained were Aniptodera chesapeakensis, Verruculina enalia, Savoryella lignicola
      and Clavatospora bulbosa. Ascochyta sp. was represented by only a single isolate.

PMID- 20136042
TI  - Bioaccumulation of lead in milk of buffaloes from Cooum River Belt in Chennai.
AB  - Bioaccumulation of heavy metals has been studied in aquatic flora and fauna to a
      greater extent than in terrestrial animals. Hence, this study was performed to
      find out whether lead was excreted in the milk of buffaloes reared near the Cooum
      belt which was fed by contaminated feed and polluted water from the nearby wells.
      The concentrations of lead in milk of buffaloes fed under farm conditions were
      also studied. The results have indicated that the ground water (0.32 microg ml(
      1)) and feed (8.62 microg g(-1)) are the sources of lead in buffalo milk (0.06
      microg ml(-1)). It revealed that one unit increases of lead in water and feed
      corresponded to an increase of 77.38 and 37.77 units respectively in milk of
      buffaloes reared near the contaminated watercourse. However, the milk of
      buffaloes from Central Cattle Breeding Farm is free from lead (0.013 microg ml(
      1)) pollution. The reason for bioaccumulation of lead in the milk of buffaloes
      reared near the sewage carrying river is due to drinking of contaminated ground
      water from wells and bore-wells dug near the river.

PMID- 20136043
TI  - Activity of phosphatases in the hemocytes of estuarine edible mudcrab, Scylla
      serrata exposed to arsenic.
AB  - Sundarbans biosphere reserve is an ecologically important area of West Bengal,
      which supports a wide variety of estuarine species including Scylla serrata
      estuarine mudcrab of economic value. In this present study, activity of
      phosphatases (acid and alkaline) of hemocytes was estimated under the sublethal
      exposure of arsenic in controlled static water environment for 1, 2, 3, 4, 7 and
      15 days of exposure. Exposure to 3 ppm of sodium arsenite for 15 days, resulted a
      maximum inhibition of activity of acid phosphatase (ACP) as 0.016 microM mg(-1)
      protein min(-1) with intermediate activity in different spans of exposure against
      the control value of 1.83 microM mg(-1) protein min(-1). Similar mode of maximum
      inhibition of activity of alkaline phosphatase (ALP) was recorded as 0.008 microM
      mg(-1) protein min(-1), when the crabs were exposed to 3 ppm of sodium arsenite
      for 15 days against the control value of 0.694 microM mg(-1) protein min(-1).
      Exposure to 1 ppm of sodium arsenite caused inhibition of activity of ACP which
      ranged from 1.76 to 0.70 microM mg(-1) protein min(-1). For 2 and 3 ppm of
      exposure activity of ACP ranged from 1.12 to 0.42 and 0.67 to 0.016 microM mg(-1)
      protein min(-1) respectively. For the activity of ALP exposure to 2 and 3 ppm of
      sodium arsenite yielded an inhibition of activity which ranged from 0.472 to
      0.279 and 0.275 to 0.008 microM mg(-1) protein min(-1) respectively. Arsenic
      exposure resulted a dose dependent decrease in the activities of both of the
      phosphatases and may be considered as a suitable biomarker of aquatic pollution
      in Sundarbans mangrove.

PMID- 20136044
TI  - Application of Trapa bipinosa for the treatment of pulp and paper industry
      effluent.
AB  - The ability of aquatic plants to absorb, translocate and concentrate metals has
      led to the development of various plant-based treatment systems. The potential to
      accumulate metals like iron, nickel, manganese and copper by Trapa bipinosa was
      assessed by subjecting them to different effluent concentrations of pulp and
      paper industry under laboratory conditions. Trapa showed the ability to
      accumulate substantial amounts of the metals during a short span of one week.
      When the plants were grown in different concentrations they caused significant
      reduction in various parameters like dissolved oxygen, biological oxygen demand,
      chemical oxygen demand, total alkalinity total hardness, chloride and sulphate.
      While there was an increase in biomass, no visible phytotoxic symptoms were shown
      by treated plants.

PMID- 20136045
TI  - Modulatory effects of garlic extract against the cyclophosphamide induced
      genotoxicity in human lymphocytes in vitro.
AB  - Cyclophosphamide (CP) is a commonly used chemotherapeutic and immunosuppressive
      agent which is used in the treatment of wide range of cancers and autoimmune
      diseases. Besides that it is a well known carcinogen. In this study by using
      chromosomal aberrations (CA) and sister chromatid exchanges (SCE) assays method,
      the modulatory effects exerted by the extract of garlic against the CP induced
      genotoxicity in the human lymphocyte cultures in vitro were tested. Three
      different doses of garlic extract were tested for their modulatory capacity on
      the mutagenecity exerted by 100 microg ml(-1) of CR The results indicate a
      significant decrease in the frequency of CA and SCE suggesting that the garlic
      extract modulates the CP induced genotoxicity in a dose dependent manner. These
      findings provide the future directions for the research on design and development
      of possible modulatory drugs containing garlic extract.

PMID- 20136046
TI  - Treatment of rayon grade pulp drain effluent by upflow anaerobic fixed packed bed
      reactor (UAFPBR).
AB  - The Rayon grade pulp (RGP) drain effluent of pulp and paper mill was studied to
      find out pollutant loading and its control measures by low cost and efficient
      treatment method. Upflow anaerobic fixed packed bed reactor (UAFPBR) with brick
      ballasts as packing material was used for this purpose. This was compared with
      conventional anaerobic treatment method. The digested slurry was taken as
      inoculum from the active cow dung biogas plant. After stabilization of the
      reactors the reduction in pollutant loading was found to be higher in UAFPBR than
      conventional anaerobic reactor (CAR). Hydraulic retention time (HRT) of 12 hr was
      optimum for the treatment of effluent when 74.5% COD and 81% BOD reduction was
      obtained. 30% inoculum concentration was best for the anaerobic treatment of RGP
      colour drain effluent. The maximum biogas production (1.37 l l(-1) of effluent)
      was when the effluent was inoculated with 30% seeding material. Thus, UAFPBR
      system was very efficient in terms of BOD, COD, TSS and TDS removal from RGP
      drain of paper mills in ambient environmental conditions.

PMID- 20136047
TI  - Cadmium induced effect on growth and physiology in halophilic phosphobacteria.
AB  - The chosen phosphobacterial species are well tolerated to the wide range of
      salinity (20-40 ppt) and found to be pure marine forms. Effect of different
      concentrations of cadmium on the growth, phosphate solubilising activity and
      content of extracellular macromolecules in eight species of phosphate
      solubilising bacteria were carried-out in the present study at optimum level of
      salinity and found that these activities are found maximum at lower
      concentrations of cadmium and further reduction in the activities were noticed at
      higher concentrations. The maximum content of total sugar was noticed in S.
      aureus at 1 ppm level of cadmium. The content of protein was found maximum in B.
      megaterium and M. roseus without the addition of cadmium and also the phosphate
      solubilizing activity was found higher in all the chosen phosphobacterial strains
      with the addition of cadmium.

PMID- 20136048
TI  - Response of ultraviolet-B and nickel on pigments, metabolites and antioxidants of
      Pisum sativum L.
AB  - Ultraviolet radiation (UV) though harmful but is an important and unavoidable
      component of terrestrial ecosystem to which plants have been exposed since their
      migration from aquatic to land habitat. Incoming UV-B radiation and heavy metals
      abundance in contaminated soils are significant environmental threat affecting
      metabolic functions of plants through generation of reactive oxygen species.
      Plants have evolved mechanisms to counteract these reactive radicals and to
      repair the damage caused by UV-B and heavy metals. This study describes the
      impact of supplemental UV-B (sUV-B) and nickel (Ni) singly and in combination on
      photosynthetic pigments, flavonoids, enzymatic and non-enzymatic antioxidants,
      metabolites and lipid peroxidation of Pisum sativum L. (pea) plants. Compared to
      the controls, both the stresses individually and in combination led to reductions
      in photosynthetic pigments, ascorbic acid, protein and catalase (CAT) activity
      whereas a reverse trend was observed for flavonoids, phenol, proline and thiol
      contents, superoxide dismutase (SOD) and peroxidase (POX) activities and lipid
      peroxidation (LPO). However, flavonoids increased significantly under individual
      exposure of sUV-B as compared to other treatments. An increase of LPO by 81%
      indicated the generation of reactive oxygen species under both the stress
      conditions. sUV-B and Ni in combination acted synergistically with stimulation of
      CAT activity by 51.6%, additively on SOD activity with increase of 16.4%, while
      other parameters showed antagonistic action of both the stresses.

PMID- 20136049
TI  - Study of genetic polymorphism in solvent exposed population and its correlation
      to in vitro effect of trichloroethylene on lymphocytes.
AB  - Trichloroethylene (TCE) is major industrial pollutant that contaminate
      environment. Its exposure may lead to hepato-renal toxicity along with the cancer
      progression. Although extensive research is done on its toxicity still not much
      is known about its genotoxic potential on humans in relation to genetic
      polymorphism. Cytochrome P450 (CYP P-450) and glutathione-S-transferases (GSTs)
      are important in cellular detoxification of TCE. Variations in gene sequences
      result in population specific regional genetic variations (polymorphism).
      Genotyping of CYP1A1, GSTM1, GSTT1 and GSTP1 polymorphism was performed in 220
      normal and 97 solvent-exposed individuals from northern part of India using real
      time PCR, PCR and restriction digestion techniques. The parameters examined to
      study genotoxicity were chromosomal aberration (CA) and cytokinesis block
      micronucleus assay (CBMN) in lymphocyte culture in vitro. The observed average
      frequencies for GSTM1 (null) and GSTT1 (null) were 41, 22 and 12.7%, respectively
      in normal subjects whereas frequencies of CYP1A1/GSTP1 with (ile/ile) or
      (ile/val) or(val/val) were found to be 76.2/52, 21.4/42.1 and 2.4/5.9%
      respectively. It was further observed that the frequencies of above genes were
      found to be similar in solvent exposed groups. The distribution frequencies of
      GST genes, when compared with other reports from various regions of India show
      variations. In vitro TCE exposure (2, 4 and or 6 mM) did not show any significant
      genotoxic effect. TCE maybe toxic due to its metabolite.

PMID- 20136050
TI  - Ultrastructural observations in gills and hepatopancreas of prawn Macrobrachium
      malcolmsonii exposed to mercury.
AB  - The juveniles of M. malcolmsonii were exposed to 24.1 microg l(-1) of Hg fora
      period of 21 days. The gills and hepatopancreas of test prawns were sampled and
      processed for electron microscopic observations. Mitochondria are the organelle
      most affected in the gills of test prawns. The number of mitochondria and the
      electron-density of the matrix were found to be less in test prawns. The in
      folding of cell membrane associated with mitochondria was absent in test prawns.
      This suggests that operation of the mitochondrial pumps was affected in the gills
      of test prawns. Vacuoles with crystalline granular inclusions were noted in the
      gills of test prawns. These are suggestive of metal-rich inorganic deposits or
      granules representing detoxified dumps of Hg. In the hepatopancreas of test
      prawns, the tubules exhibit vacuoles with granular inclusion and the cell
      cytoplasm contains electron-dense granules, which indicate a storage
      detoxification of Hg. The mitochondria were shrunken in the hepatopancreas of
      test prawns. This suggests attenuation of its function. The rough endoplasmic
      reticulum appeared vesiculated and dilated. These reactions denote the
      hyperactivity of the rough endoplasmic reticulum. Membranous whorl-like
      structures with myelin fibers and residual bodies were seen in the hepatopancreas
      of test prawns. Such structures indicate the involvement of lysosomal breakdown
      in detoxification process. The ultrastructural alterations are suggestive of the
      operation of compensatory mechanisms within the test prawns to enable it to
      tolerate Hg toxicity. However these alterations would have an impact on the
      cellular integrity of the gills and hepatopancreas and such alterations can be
      taken as 'biomarkers' for assessing Hg pollution in the aquatic environment.

PMID- 20136051
TI  - Water quality assessment of open wells in and around Chavara industrial area,
      Quilon, Kerala.
AB  - Water quality of four open wells representing four localities around the Kerala
      Minerals and Metals Ltd industrial area, Chavara, Quilon district was studied
      fora period of six months from December, 2006 to May 2007 to assess the
      suitability of the well waters for domestic purposes. The well waters exhibited
      high BOD (average values from 12.87-15.96 mg l(-1)), COD (666.67-796.67 mg l(
      1)), TDS (500-1466.67mg l(-1)), total hardness (110-835 mg l(-1)), nitrate (1.12
      4.97 mg l(-1)), calcium (30.59-271.22 mg l(-1)), phosphate (0.19-0.48 mg l(-1))
      and free CO2 (49.13-102.47 mg l(-1)) and low dissolved oxygen (2.63-3.13 mg l(
      1)). Heavy metal analysis revealed that the third and fourth wells are free from
      heavy metal pollution. Coliform test showed bacterial contamination in all the
      wells. The values of BOD, COD, TDS and phosphate exceeded the maximum permissible
      limits and the dissolved oxygen was much lower than the desirable limit in all
      the well waters. Hence all the four well waters are found unsuitable for domestic
      purposes as it is confirmed by water quality index. The use of waters of open
      wells in and around the industrial area may cause health hazards to nearby
      inhabitants.

PMID- 20136052
TI  - Halophilic (aerobic) bacterial growth rate of mangrove ecosystem.
AB  - Mangroves are woody specialized trees of tropics and are valuable flora
      contributing to economical, ecological, scientific and cultural resources. They
      thrive in salty environments like coastal regions and are aid towards disaster
      management facing the onslaught of giant waves such as Tsunami. Analysis of
      mangrove soil on the banks of the Adyar river behind the Theosophical society
      campus, Adyar, Chennai, India, gave a startling revelation of microorganisms that
      can tolerate different salinity ranges. Previous studies in Pichavaram delta,
      have reported bacterial isolates such as nitrogen fixing bacteria, halophiles and
      several others. However their efficiency in the growth of mangrove forest has
      been studied to a lesser extent. The present study has been designed and
      formulated to estimate halophilic (aerobic) bacterial load from mangroves soil
      sample based on depth and salinity of the soil and further the efficiency if any
      of these isolates in the growth of mangroves. Results have been correlated and a
      cohesive conclusion reached for further intensive research. This study throws
      light on the ecology of the bacterial population in the coastal marine
      environment inhabited bymangroves and its possible role in disaster mitigation.

PMID- 20136053
TI  - Physico-chemical studies of River Pumba and distribution of prawn, Macrobrachium
      rosenbergii.
AB  - Physico-chemical factors of river Pumba, Kerala has been analyzed to understand
      its relationship with the distribution of Giant river prawn, Macrobrachium
      rosenbergii in the water body. Water samples were taken from two sites on the
      basis of presence and absence of juveniles. Analysis of temperature, pH,
      turbidity, dissolved oxygen, dissolved carbon dioxide and salinity of the water
      samples revealed that except salinity all the other parameters were identical in
      both the regions. Salinity was high i.e., 5-8 per thousand in lower Kuttanad
      region, where juveniles were seen. In upper Kuttanad region, where only adults
      were located, the salinity was of freshwater pattern i.e., 2.1-2.9 per thousand.
      The gut content analysis of M. rosenbergii in both the regions showed similar
      food pattern. The study reveals the significance of a water body with high saline
      region for breeding purpose and low saline region i.e., freshwater pattern for
      adult prawns in the life cycle of M. rosenbergii.

PMID- 20136054
TI  - Fish diversity and its conservation in major wetlands of Mysore.
AB  - The paper highlights the fish diversity in major wetlands of Mysore district,
      Karnataka, India and its conservation status. Forty-five species of fishes
      belonging to 15 families, 31 genera have been identified. Fish species belonging
      to genus Puntius were more common in many of these lakes. However it was observed
      that the fish diversity was decreasing since last two years unprecedently mainly
      due to manifold human activities. Fish diversity in the lakes is becoming rare
      and about seven species were identified as endangered. Out of the 45 identified
      fishes, six fish species were identified as threatened species. Tork hudree, also
      known as Deccan mahseer and seven other species were identified as vulnerable
      fish species. Though there were 40 species of fish endemic to this region, their
      number decreased with introduction of more exotic species. Conservation of
      endemic fishes, propagation of endangered and threatened fishes should be
      therefore, undertaken to preserve and protect fish diversity in the wetlands of
      Mysore district.

PMID- 20136055
TI  - Assessing environmental degradation of montane riparian zones in Greece.
AB  - A survey of 218 woody vegetation plots at 109 streamside sites was undertaken to
      describe anthropogenic degradation of riparian zone woodlands in the mountains of
      mainland Greece. Two assessment indices and specific anthropogenic pressure
      variables were employed and they showed good correlations at both the site and
      river segment scales. It was demonstrated through the Spanish Riparian Forest
      Quality Index (Qualitat de Bosc de Riber: QBR) that most riparian zones were in
      moderate or good condition, although extremely few sites were of high ecological
      status. Most riparian sites were affected by several anthropogenic pressures,
      some pressures produce notable degradation beyond the site-scale (i.e. at the
      river segment scale). This work provides a summary of the first wide-ranging
      vegetation-based assessment of montane riparian zones in Greece; the results
      support the use of site-based rapid assessment protocols along-side aquatic
      ecological status surveys.

PMID- 20136056
TI  - Impact of organophosphorus insecticide, malathion on the progeny sex ratio of
      Pimpla turionellae L.
AB  - The effects of 0.001, 0.01, 0.1 and 0.5 ppm concentrations of malathion, an
      organophosphorus insecticide, viewed over the course of the experiment, on adult
      emergence and sex ratios of emerging adults of the parasitic wasp, Pimpla
      turionellae L. (Hymenoptera: Ichneumonidae) were investigated. Diets which
      contain 0.001 and 0.01 ppm malathion significantly increased the total adult
      emergence on day 13, 28 and 31 when compared to control diet. Although 0.01 and
      0.1 ppm malathion increased the female emergence, higher concentration of
      malathion (0.5 ppm) significantly decreased the female emergence. Adult female
      emergence significantly decreased on day 10, 16 and 25 in the group which was fed
      with the meridic diet containing 0.5 ppm malathion. This study indicated that
      orally administrated high concentration of malathion (0.5 ppm) significantly
      decreased female emergence of P. turionellae.

PMID- 20136057
TI  - Chemical composition of tomato (Solanum lycopersicum) stalk and suitability in
      the particleboard production.
AB  - This study examined chemical composition of tomato stalks and their possible
      feasibility in the production of particleboard. Three-layer experimental
      particleboards with density of 0.53, 0.63, and 0.73 g cm(-3) were manufactured
      from tomato stalks using certain ratios of urea formaldehyde (UF) and melamine
      urea formaldehyde (MUF) adhesives. Modulus of elasticity (MOE), modulus of
      rupture (MOR), internal bond strength (IB), thickness swelling (TS) properties of
      the boards were evaluated, and a statistical analysis was performed in order to
      examine possible feasibility of these stalks in commercial particleboard
      manufacturing. The experimental results have shown that production of general
      purpose particleboard used in dry conditions using tomato stalks is technically
      viable. The results of the study demonstrate that tomato stalks can be an
      alternative raw material source for particleboard industry. Use of agricultural
      waste such as tomato stalk can help solving waste management problems and
      contribute conservation of natural resources.

PMID- 20136058
TI  - An environmentally friendly organosolv (ethanol-water) pulping of poplar wood.
AB  - In this study pulp production from the fast growing plant, poplar; was examined
      for organosolv pulping with or without catalysts. In order to find the optimum
      cooking conditions, 18 different cooking experiments were carried out. The effect
      of ethanol ratio, cooking time as well as catalyst was studied. It was observed
      that even at lower temperature (90 degrees C), cooking without catalyst was able
      to cause sufficient defiberization. It was seen that the increasing proportion of
      catalyst and cooking temperature resulted in an increased delignification.
      However in the case of using 0.02% acid catalyst pulp yield and viscosity were
      lowered to an unacceptable level. The most important cooking factors were found
      to be the proportion of acid catalyst. Furthermore, the delignification
      performance was found to be depending on the pH of the black liquor. In a result,
      the optimum pulp properties were obtained by cooking at 180 degrees C for 90 min
      with 50% ethanol mixture without catalyst. The pulp yield was noted as 44.49%,
      viscosity was 892 cm2 g(-1) and the kappa number was 67.

PMID- 20136059
TI  - Environmental factors as influencing vegetation communities in Acipayam district
      of Turkey.
AB  - In this study a data set from Mediterranean mountain forests of southern
      Anatolia, consisting of species cover and environmental measures in 99 sample
      plots was analyzed with cluster analysis, indicator species analysis, MRPP, NMDS
      and sperman rank correlation. Results illustrated two vegetation gradients
      related to factor complexes of altitude-landform and parent material-land surface
      smoothness. Axis I of the ordination was strongly related to limestone,
      serpantine, conglomerate, marl from parent material group, middle slope from
      slope position group, concave, convex, linear and undulate from landform group,
      AI, AII, AIII and AIV from altitude group, and rocky and erosion pavement from
      land surface smoothness group. Axis II was strongly related to limestone,
      serpantine, smooth surface, rocky surface and AIII.

PMID- 20136060
TI  - Effect of pesticide residues on health and blood parameters of farm workers from
      rural Gadap, Karachi, Pakistan.
AB  - The samples were collected from 83 persons on 1 day (reading-I), 7 days (reading
      II) and 30 days (reading-III) engaged in pesticide spraying in fourteen different
      fruit and vegetable farm stations located in the orchards of Gadap (rural area),
      Karachi-Pakistan. In the present study 26 workers out of 83 who were exposed to
      different pesticides (ie., cypermethrin, deltamethrin, polytrin-C, diazninon,
      monocrotophos, DDT and DDE) were compared with 25 healthy control persons.
      Different blood parameters were determined in comparison to control subjects. The
      results indicate some alterations in blood indices in allthe pesticide exposed
      persons, and only two persons from two different stations were affected severely
      and therefore their Hb, MCV MCHC, TLC, monocyte and neutrophil counts increased
      significantly. High lymphocyte count was noted in almost all the exposed persons.
      Platelets count was also found high in few persons but Hb, MCV, MCH, TLC, RBC and
      neutrophil counts significantly decreased in such persons. Exposure of multiple
      pesticides for prolong period has also affected the health of exposed persons and
      produced dermatological, hepatic, nephritic, respiratory and other clinical
      disorders reflecting the toxic effects of pesticides. Our findings indicate that
      indiscriminate use of pesticides in farming environments must be regularly
      assessed and farm workers must be trained for safe use of pesticides.

PMID- 20136061
TI  - Evaluation of trophic state of Lake Uluabat, Turkey.
AB  - Lake Uluabat, which is located in Marmara region, is one of the most productive
      lakes in Turkey. Due to concerns about potential pollution resulting from
      watershed sources and adjacent agricultural lands, a study of the trophic state
      of lake Uluabat was conducted during the period February 2003 to January 2004.
      Total nitrogen (TN), total phosphorus (TP), Secchi disc depth (SD) and
      chlorophyll a (Chl a) were analyzed monthly in order to assess the trophic state
      of the lake. According to calculated nutrient ratios, phosphorus was found to be
      the primary limiting nutrient in lake Uluabat. Carlson's trophic state index
      values, based on TP, SD and Chl a, indicated that lake Uluabat is an eutrophic
      system.

PMID- 20136062
TI  - Tree species diversity of natural mixed stands in eastern Black Sea and western
      Mediterranean region of Turkey.
AB  - Differences in free species diversity of natural mixed stands were compared
      between the eastern Black sea region (EBSR) and western Mediterranean region
      (WMR) of Turkey, to clarify the effects of differences in forest structure,
      focusing on the tree species occurring in each. Species diversity with special
      reference to stand structure, of natural mixed stands was quantified by Shannon
      Wiener index (H'), equitability index (J'), and species richness index (R). All
      species diversity indices were significantly higher in EBSR than in WMR.
      According to the coefficients of homogeneity (CH), stands in EBSR are generally
      have uneven-aged stand structure, but in WMR even-aged stand structure is more
      common. Uneven-aged stands have more tree species diversity than even-aged
      forests due to complex vertical forest structure and species composition.
      According to Pearson's coefficients, species diversity indices and richness are
      closely related the average stand diameter (Ds) in uneven-aged stands of EBSR,
      but average stand diameter (Ds), age (A), and stand density (SDI) are the most
      important stand parameters in even-aged stands of WMR in Turkey.

PMID- 20136063
TI  - Generalized height-diameter models for Picea orientalis L.
AB  - The purpose of this paper is to compare major models for height estimation of
      Picea orientalis L trees based on the individual tree diameter and certain other
      stand variables. The data were collected from 440 trees of pure and even-aged P.
      orientalis stands that are located near Artvin in the northeastern part of
      Turkey. The data from 406 trees were used for model development and the remaining
      data were reserved for model validation. A total of 17 non-linear models were
      fitted to 406 trees. Mean square errors and R2 values for the 17 models showed
      that some models roduced similar height estimation. The model [8] gave the best
      height estimates for P. orientalis with the highest R2 (0.8703) and the lowest
      mean square error (5.47). Validation of the models using independent data sets
      showed that model [8] and [16] gave the best height predictions for this
      particular dataset.

PMID- 20136064
TI  - Numerical interdependence in pH, acidity and alkalinity of a polluted river
      water.
AB  - Acidity and alkalinity are independent parameters and they directly or indirectly
      regulate the pH of a medium. These are the prime factors which control the nature
      of the reactions in a medium. The present study was designed to explore the
      numerical interdependence of the three parameters and also, to develop the
      regression models. For physico-chemical analysis of the selected parameters,
      water quality of a polluted tropical river was analysed fortnightly, for complete
      one year. Correlation coefficients between pH-acidity and acidity-alkalinity were
      negative while that between pH and alkalinity were positive. The value calculated
      by the developed multiple regression models, explain pH, acidity and alkalinity
      up to 57, 65 and 79% respectively, suggesting their utility and relevance.

PMID- 20136065
TI  - Conformational analysis of a model for the trans-fused FGH ether rings in
      brevetoxin A.
AB  - We have applied the Low Mode:Monte Carlo (LM:MC) conformational search method to
      an investigation of the low energy structures for 3R,4aS,7aR,11aS,12aR)-11a
      methyl-3-phenyldecahydro-1H-[1,3]dioxino[5,4-b]pyrano[2,3-g]oxocine, 3, a model
      for the FGH rings in brevetoxin A, a potent marine toxin. Searches performed
      using a variety of classical force field-solvent combinations yielded ensembles
      containing between 30 and 60 structures with the central G-ring adopting the
      crown, twist-crown, boat-chair, and boat conformations. The lowest energy
      structure depended on the force field-solvent treatment, and the twist-crown and
      boat-chair conformers were typically lowest in energy. B3LYP/6-31G** geometry
      optimizations using the SCRF continuum solvent model confirmed these structures
      but indicated that the crown was the energetically preferred conformer with the
      boat-chair lying within 1.4 kcal/mol.

PMID- 20136066
TI  - Effects of DPH on DPPC-cholesterol membranes with varying concentrations of
      cholesterol: from local perturbations to limitations in fluorescence anisotropy
      experiments.
AB  - We have used atomistic molecular dynamics simulations to consider 1,6-diphenyl
      1,3,5-hexatriene (DPH) fluorescent probes in a fluid
      dipalmitoylphosphatidylcholine bilayer with 5 and 20 mol % cholesterol (CHOL). We
      show that while DPH affects a number of membrane properties, the perturbations
      induced by DPH depend on the concentration of cholesterol in a membrane. For
      example, we find DPH to influence the mass density distribution of lipids across
      the membrane and to promote the ordering of acyl chains around the probe. Yet,
      these perturbations get relatively weaker for increasing cholesterol
      concentration. Meanwhile, we also find that the commonly used analysis in terms
      of the Brownian rotational diffusion (BRD) model with Legendre polynomials to
      interpret fluorescence anisotropy (FA) experiments is sensitive to the amount of
      cholesterol. For small concentrations of cholesterol, the analysis of FA turns
      out to yield a relatively good approximation of the correct orientational
      distribution of DPH. However, for a CHOL concentration of 20 mol %, we find that
      the FA analysis fails to yield the true orientational distribution of DPH, the
      disagreement being substantial. The results suggest that in highly ordered
      membrane domains, the view given by FA analysis using the BRD model is likely
      reliable in a qualitative sense, but the quantitative description deviates
      substantially from the correct one. The present results imply that FA studies for
      the orientational distribution of DPH should be interpreted with great care.

PMID- 20136067
TI  - Considerable change of fluorescence properties upon multiple binding of coralyne
      to 4-sulfonatocalixarenes.
AB  - The interaction of coralyne, an analogue of natural protoberberine alkaloids,
      with 4-sulfonatocalixarenes (SCXn) was studied in aqueous solution at pH 2 to
      reveal the major factors determining the stability, stoichiometry, and
      fluorescent properties of the species formed. Addition of SCXn to coralyne
      solution brought about remarkable fluorescence intensity diminution and
      hypochromism in the 300-440 nm absorption domain. SCXn hosts were capable of
      binding as many coralyne molecules as the number of their hydroxybenzenesulfonate
      units. The SCXn-promoted interaction among coralyne molecules was evidenced by
      the appearance of a long-lived fluorescence component. In dilute alkaloid
      solution, 1:1 and 1:2 coralyne/4-sulfonatocalix[4]arene complexes were formed,
      but only 1:1 association occurred with 4-sulfonatocalix[8]arene. Time-resolved
      fluorescence measurements demonstrated that photoinduced electron transfer from a
      hydroxybenzenesulfonate moiety to the singlet-excited coralyne can compete
      efficiently with the other deactivation processes.

PMID- 20136068
TI  - Dynamics in organic ionic liquids in distinct regions using charged and uncharged
      orientational relaxation probes.
AB  - The temperature-dependent fluorescence anisotropy decay (orientational
      relaxation) of perylene and sodium 8-methoxypyrene-1,3,6-sulfonate (MPTS) were
      measured in a series of 1-alkyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide (alkyl = ethyl, butyl, hexyl, octyl) organic
      room temperature ionic liquids (RTIL). The two fluorescent probe molecules
      display markedly different rotational dynamics when analyzed using Stokes
      Einstein-Debye theory, demonstrating that they are located in distinct
      environments within the RTILs and have very different interactions with their
      surroundings. Perylene rotates with subslip behavior, becoming increasingly
      subslip as the length of ionic liquid alkyl chain is increased. The dynamics
      approach those of perylene in an organic oil. In contrast, MPTS shows superstick
      behavior, likely reflecting very strong coordination with the RTIL cations. These
      results are consistent with different elements of rotational friction within the
      ionic liquid structure, which are available to solutes depending on their
      chemical functionality.

PMID- 20136069
TI  - DNA melting in small-molecule-DNA-hybrid dimer structures: experimental
      characterization and coarse-grained molecular dynamics simulations.
AB  - When DNA hybridization is used to link together nanoparticles or molecules, the
      melting transition of the resulting DNA-linked material often is very sharp. In
      this paper, we study a particularly simple version of this class of material
      based on a small-molecule-DNA-hybrid (SMDH) structure that has three DNA strands
      per 1,3,5-tris(phenylethynyl)benzene core. By varying the concentration of the
      SMDHs, it is possible to produce either SMDH dimers or bulk aggregates, with the
      former having highly packed duplex DNA while the latter has an extended network.
      Melting measurements that we present show that the dimers exhibit sharp melting
      while the extended aggregates show broad melting. To interpret these results, we
      have performed coarse-grained molecular dynamics (CGMD) studies of the dimer
      melting and also of isolated duplex melting using CGMD potentials that have
      either implicit or explicit ions. Details of the melting simulation technology
      demonstrate that the simulations properly describe equilibrium transitions in
      isolated duplexes. The results show that the SMDH dimer has much sharper melting
      than the isolated duplex. Both implicit and explicit ion calculations show this
      effect, but the explicit ion results are sharper. An analytical model of the
      melting thermodynamics is developed which shows that the sharp melting is
      entropically driven and can be understood primarily in terms of the differences
      between the effective concentrations of the DNA strands for intracomplex
      hybridization events compared to intermolecular hybridization.

PMID- 20136070
TI  - Irreversible insertion of benzonitrile into platinum(II)-nitrogen bonds of
      nucleobase complexes. Synthesis and structural characterization of stable
      azametallacycle compounds.
AB  - Deprotonation of 1-methylcytosine (1-MeCy) and 9-methyladenine (9-MeAd) promoted
      by cis-[L(2)Pt(mu-OH)](2)(NO(3))(2) (L = PPh(3), PMePh(2), (1)/(2)dppe) in PhCN
      causes the irreversible insertion of a nitrile molecule into the Pt-N4 and Pt-N6
      bonds of the cytosinate and adeninate ligands, respectively, to form the stable
      azametallacycle complexes cis-[L(2)PtNH=C(Ph){1-MeCy(-2H)}]NO(3) (L = PPh(3), 1;
      PMePh(2), 2; (1)/(2)dppe, 3) and cis-[L(2)PtNH=C(Ph){9-MeAd(-2H)}]NO(3) (L =
      PPh(3), 4; PMePh(2), 5) containing the deprotonated form of the molecules (Z)-9-N
      (1-methyl-2-oxo-2,3-dihydropyrimidin-4(1H)-ylidene)benzimidamide and (Z)-N-(9
      methyl-1H-purin-6(9H)-ylidene)benzimidamide. Single-crystal X-ray analyses of 2
      and 4 show the metal coordinated to the N3 cytosine site [Pt-N3 = 2.112(7) A] and
      to the N1 site of adenine [Pt-N1 = 2.116(6) A] and to the nitrogen atom of the
      inserted benzonitrile [Pt-N2 = 2.043(6) and 2.010(6) A in 2 and 4, respectively],
      with the exocyclic nucleobase amino nitrogen bound to the carbon atom of the CN
      group. Complex 2, in solution, undergoes a dynamic process related to a partially
      restricted rotation around Pt-P bonds, arising from a steric interaction of the
      oxygen atom of the cytosine with one ring of the phosphine ligands. The reaction
      of 4 with acetylacetone (Hacac) causes the quantitative protonation of the
      anionic ligand, affording the acetylacetonate complex cis
      [(PPh(3))(2)Pt(acac)]NO(3) and the free benzimidamide NH=C(Ph){9-MeAd(-H)}. In
      the same experimental conditions, complex 3 reacts with Hacac only partially.

PMID- 20136071
TI  - La2U2Se9: an ordered lanthanide/actinide chalcogenide with a novel structure
      type.
AB  - The compound La(2)U(2)Se(9) was obtained in high yield from the stoichiometric
      reaction of the elements in an Sb(2)Se(3) flux at 1123 K. The compound, which
      crystallizes in a new structure type in space group Pmma of the orthorhombic
      system, has a three-dimensional structure with alternating U/Se and La/Se layers
      attached via three independent, infinite polyselenide chains. The U atom has a
      monocapped square antiprismatic coordination of Se atoms, whereas one La atom is
      bicapped square prismatic and the other La atom is trigonal prismatic.
      La(2)U(2)Se(9) displays an antiferromagnetic transition at T(N) = 5 K; above 50
      K, the paramagnetic behavior can be fit to the Curie-Weiss law, yielding a
      mu(eff) of 3.10(1) mu(B)/U. The low-temperature specific heat of La(2)U(2)Se(9)
      exhibits no anomalous behavior near the Neel temperature that might indicate long
      range magnetic ordering or a phase transition. X-ray absorption near-edge
      structure (XANES) spectra have confirmed the assignment of formal oxidation
      states of +III for lanthanum and +IV for uranium in La(2)U(2)Se(9).

PMID- 20136072
TI  - Current status of the AMOEBA polarizable force field.
AB  - Molecular force fields have been approaching a generational transition over the
      past several years, moving away from well-established and well-tuned, but
      intrinsically limited, fixed point charge models toward more intricate and
      expensive polarizable models that should allow more accurate description of
      molecular properties. The recently introduced AMOEBA force field is a leading
      publicly available example of this next generation of theoretical model, but to
      date, it has only received relatively limited validation, which we address here.
      We show that the AMOEBA force field is in fact a significant improvement over
      fixed charge models for small molecule structural and thermodynamic observables
      in particular, although further fine-tuning is necessary to describe solvation
      free energies of drug-like small molecules, dynamical properties away from
      ambient conditions, and possible improvements in aromatic interactions. State of
      the art electronic structure calculations reveal generally very good agreement
      with AMOEBA for demanding problems such as relative conformational energies of
      the alanine tetrapeptide and isomers of water sulfate complexes. AMOEBA is shown
      to be especially successful on protein-ligand binding and computational X-ray
      crystallography where polarization and accurate electrostatics are critical.

PMID- 20136073
TI  - Transcriptional effects of prenatal and neonatal exposure to PFOS in developing
      rat brain.
AB  - Perfluorooctane sulfonate (PFOS), a persistent and bioaccumulative compound, is
      widely distributed in the environment. To explore the molecular mechanism of
      neonatal neurotoxic effects, we evaluated the transcriptional effects of prenatal
      and neonatal exposure to PFOS in developing rat brain by performing gene
      expression profiling in the cerebral cortex. Dams received 3.2 mg/kg PFOS in
      their feed from gestational day 1 (GD1) to weaning (PND 21). Pups then had free
      access to treated feed until PND 35. Six Illumina RatRef-12 Expression BeadChips
      were used to identify gene expression changes on postnatal days (PNDs) 1, 7, and
      35. Significantly affected genes (P < 0.05) were involved in neuroactive ligand
      receptor interaction, calcium signaling pathways, cell communication, long-term
      potentiation/depression, the cell cycle, and peroxisome proliferator-activated
      receptor (PPAR) signaling. To compare prenatal and lactational exposure
      contributions to transcriptional effects, a subset of altered genes obtained from
      the gene-profile study that represented neurobiological functions was analyzed
      using RT-PCR in a follow-up cross-foster study lasting from PND1 to 21. Prenatal
      and postnatal exposure to PFOS caused potential neurotoxicity as demonstrated by
      developmentally different global transcriptional changes. Prenatal exposure was
      more effective in altering expression of several genes. Also, transcriptional
      effects of PFOS exposure on neurodevelopment occurred primarily by disrupting the
      neuroendocrine system.

PMID- 20136074
TI  - Determining exposure history of northern pike and walleye to tailings effluence
      using trace metal uptake in otoliths.
AB  - Determining the effects of mining activity on fish populations is complicated by
      the uncertainty of fish residency in an affected area. Otoliths are considered to
      be metabolically inert and can contain complete chemical records of environments
      in which individuals have lived. When coupled with the annular structure,
      otoliths provide temporal information to the history of exposure to pollutants.
      In this preliminary study, northern pike and walleye otoliths collected from two
      lakes adjacent to base metal mine tailings at Lynn Lake, Manitoba, Canada, were
      analyzed using laser ablation inductively coupled plasma mass spectrometry to
      determine background levels of trace metals. The presence of overlapping Zn, Cu,
      and Pb peaks above background levels in some otoliths is interpreted as a record
      of elevated levels in the environment. These otoliths provided a record of the
      history of fish movement into and out of the affected area.

PMID- 20136075
TI  - Fungal PAH-metabolites resist mineralization by soil microorganisms.
AB  - This study investigated the mineralization of water-soluble polycyclic aromatic
      hydrocarbon (PAH) metabolites produced by the soil fungus Cunninghamella elegans.
      Eleven soil fungi were screened for their ability to metabolize (14)C
      phenanthrene, (14)C-fluoranthene, and (14)C-pyrene into water-soluble compounds.
      Eight fungi produced water-soluble metabolites from all or some of the PAHs. The
      composition of the water-soluble PAH-metabolites from the most effective
      solubilizer C. elegans was analyzed by an ultraperformance liquid chromatograph
      interfaced to a quadrupole time-of-flight mass spectrometer. Thirty-eight
      metabolites were detected. All of 34 identified metabolites were sulfate
      conjugated. The mineralization of (14)C-metabolites, produced by C. elegans, was
      compared to mineralization of the parent (14)C-PAHs in soil slurries. It was
      hypothesized that the increased bioavailability and metabolic activation of the
      metabolites would increase mineralization in soil slurries compared to
      mineralization of the parent PAHs. Unexpectedly, the mineralization of the (14)C
      metabolites was in all cases extremely slow compared to the mineralization of the
      parent (14)C-PAHs. Slow (14)C-metabolite mineralization was not caused by
      metabolite toxicity, neither was cometabolic mineralization of (14)C-metabolites
      stimulated by the presence of active PAH-degraders. High water solubility, low
      lipophilicity, and extremely slow mineralization of the metabolites indicate a
      potential problem of leaching of fungal PAH-metabolites to the groundwater.

PMID- 20136076
TI  - A contractile electronic switch made of DNA.
AB  - Double-helical DNA has been shown to conduct both electrons and electron holes,
      the latter over distances of >20 nm. DNA is thus a material of significant
      interest for the bottom-up construction of nanocircuitry. Here, we describe a
      contractile DNA nanoswitch, which can toggle between a structurally extended
      "off" state and a contracted "on" state, with a 40-fold conductivity difference
      between the two. To turn on, two short motifs of guanine-guanine mismatches in an
      otherwise standard double helix synapse to form a conductive G-quadruplex,
      bypassing an insulating element within the helix. This switch can be turned
      repeatedly on by treatment with millimolar concentrations of K(+) and turned off
      by sequestration of the K(+) by a crown ether. Circular dichroism and thymine
      thymine photocross-linking experiments reveal that strand orientations within the
      on state G-quadruplex are wholly antiparallel and that the two conductive double
      helices interface with the same face of the quadruplex. Although this DNA
      nanoswitch is chemically gated, it should be adaptable to other kinds of gating
      and thus serve as a prototype for increasingly sophisticated and complex
      electronic devices made of DNA.

PMID- 20136077
TI  - Formation of the phenyl radical [C6H5(X(2)A1)] under single collision conditions:
      a crossed molecular beam and ab initio study.
AB  - Reactions of dicarbon molecules (C(2)) with C(4)H(6) isomers such as 1,3
      butadiene represent a potential, but hitherto unnoticed, route to synthesize the
      first aromatic C(6) ring in hydrocarbon flames and in the interstellar medium
      where concentrations of dicarbon transient species are significant. Here, crossed
      molecular beams experiments of dicarbon molecules in their X(1)Sigma(g)(+)
      electronic ground state and in the first electronically excited a(3)Pi(u) state
      have been conducted with 1,3-butadiene and two partially deuterated counterparts
      (1,1,4,4-D4-1,3-butadiene and 2,3-D2-1,3-butadiene) at two collision energies of
      12.7 and 33.7 kJ mol(-1). Combining these scattering experiments with electronic
      structure and RRKM calculations on the singlet and triplet C(6)H(6) surfaces, our
      investigation reveals that the aromatic phenyl radical is formed predominantly on
      the triplet surface via indirect scattering dynamics through a long-lived
      reaction intermediate. Initiated by a barrierless addition of triplet dicarbon to
      one of the terminal carbon atoms of 1,3-butadiene, the collision complex
      undergoes trans-cis isomerization followed by ring closure and hydrogen migration
      prior to hydrogen atom elimination, ultimately forming the phenyl radical. The
      latter step emits the hydrogen atom almost perpendicularly to the rotational
      plane of the decomposing intermediate and almost parallel to the total angular
      momentum vector. On the singlet surface, smaller contributions of phenyl radical
      could not be excluded; experiments with partially deuterated 1,3-butadiene
      indicate the formation of the thermodynamically less stable acyclic
      H(2)CCHCCCCH(2) isomer. This study presents the very first experimental evidence,
      contemplated by theoretical studies, that under single collision conditions an
      aromatic hydrocarbon molecule can be formed in a bimolecular gas-phase reaction
      via reaction of two acyclic molecules involving cyclization processes at
      collision energies highly relevant to combustion flames.

PMID- 20136078
TI  - Glycodynamers: dynamic polymers bearing oligosaccharides residues--generation,
      structure, physicochemical, component exchange, and lectin binding properties.
AB  - Dynamic glycopolymers have been generated by polycondensation through
      acylhydrazone formation between components bearing lateral bioactive
      oligosaccharide chains. They have been characterized as bottlebrush type by cryo
      TEM and SANS studies. They present remarkable fluorescence properties whose
      emission wavelengths depend on the constitution of the polymer and are tunable by
      constitutional modification through exchange/incorporation of components, thus
      also demonstrating their dynamic character. Constitution-dependent binding of
      these glycodynamers to a lectin, peanut agglutinin, has been demonstrated.

PMID- 20136079
TI  - Development of an activity assay for discovery of inhibitors of
      lipopolysaccharide transport.
AB  - The outer membrane of gram-negative bacteria contains an outer leaflet composed
      of lipopolysaccharide (LPS) that is transported to this location by a pathway
      that is essential for viability. It has been suggested that inhibitors of this
      pathway could be useful antibiotics. Herein we reconstitute the activity of the
      ATPase component (LptB) of the ABC transporter that initiates LPS transport and
      assembly. We developed a high-throughput assay and screened a library of kinase
      inhibitors against LptB. We identified two classes of ATP-competitive inhibitors.
      These are the first inhibitors of the ATPase component of any bacterial ABC
      transporter. The small-molecule inhibitors will be very useful tools for further
      biochemical studies of the proteins involved in LPS transport and assembly.

PMID- 20136080
TI  - Proton spin-lattice relaxation in silkworm cocoons: physisorbed water and serine
      side-chain motions.
AB  - The molecular dynamic behavior of silkworm cocoons produced by a single Bombyx
      mori strain was investigated by means of high- and low-resolution solid-state NMR
      experiments. Cocoons with different moisture content were prepared to study the
      effects of physisorbed water on their molecular dynamics in the MHz regime, which
      was probed through the measurement of (1)H T(1) relaxation times at 25 MHz in the
      25-95 degrees C temperature range. The water content of the different samples was
      determined from the analysis of (1)H free-induction decays. In addition to the
      rotation of methyl groups, mostly from alanine, and to the reorientation of
      physisorbed water molecules, already identified in previous works as relaxation
      sinks, the reorientation of serine side-chains was here found to contribute to
      (1)H T(1) above room temperature. The analysis of the trends of (1)H T(1) versus
      temperature was carried out in terms of semiempirical models describing the three
      main motional processes, and indicated that methyl rotation, water reorientation
      and serine side-chain motions are the most efficient relaxation mechanisms below
      0 degrees C, between 0 and 60 degrees C, and above 60 degrees C, respectively.
      The activation energies were found to decrease passing from serine to water to
      methyl motions.

PMID- 20136081
TI  - Coronene nanophase within coordination spheres: increased solubility of C60.
AB  - A 4.6 nm-sized coordination sphere confines 24 pendant coronene molecules at its
      core. The confined coronene molecules are fluid, forming a liquid "coronene
      nanodroplet" that could never exist in bulk. C(60) dissolves in this nano solvent
      with a high local concentration.

PMID- 20136082
TI  - Comparative study of high-linoleic acid vegetable oils for the production of
      conjugated linoleic acid.
AB  - Conjugated linoleic acid (CLA) is found in small quantities in dairy and beef
      products. Obtaining optimum dietary CLA levels from these sources requires an
      increased intake of saturated fat. A 20% CLA soy oil was produced by UV
      photoisomerization of soy oil linoleic acid (LA), which is naturally low in
      saturated fat, but no other high-LA vegetable oils have been studied for their
      potential as CLA-rich oils. The objectives of this research were to (1) compare
      flax, sunflower, corn, soy, and high-LA safflower oils as sources of CLA-rich
      vegetable oils using laboratory-scale equipment, (2) compare CLA yields obtained
      by laboratory-scale and pilot-scale equipment, and (3) compare the oxidative
      stabilities of laboratory-scale processed oils. High-LA safflower oil produced
      the most CLA; soy oil produced slightly less, followed by corn, with flax
      producing very little and sunflower none at all. Minor oil components and
      turbidity reduced CLA yields, suggesting that oils should be highly refined
      before CLA production. The pilot-scale system was more effective than the
      laboratory-scale system due to greater light exposure and larger surface area to
      volume ratio of the oil samples. The oxidative stabilities of high-LA safflower
      oil and soy oil were similar before or after irradiation, indicating that these
      oils are the most suitable for high-CLA production.

PMID- 20136083
TI  - In vitro digestion of Cry1Ab proteins and analysis of the impact on their
      immunoreactivity.
AB  - A pepsin resistance test performed at pH 1.2 and with high pepsin to protein
      ratio is one of the steps of the weight-of-evidence approach used for assessment
      of allergenicity of new proteins. However, the use of other in vitro
      digestibility tests, performed in more physiologically relevant conditions and in
      combination with immunological assays so as to increase the value of the
      information gained from the studies of stability of a novel protein to digestion
      for the overall allergenicity assessment, has been proposed. This study then
      aimed to investigate the stability to digestion of Cry1Ab protoxin and toxin,
      insecticidal proteins expressed in genetically modified crops, using simulated
      gastric fluid (SGF) at different pH values and pepsin-to-substrate ratios, in the
      presence or absence of physiological surfactant phosphatidylcholine (PC).
      Electrophoresis and immunoblot patterns and residual immunoreactivity of digesta
      were analyzed. Although Cry1Ab protoxin is extensively degraded at pH 1.2 with
      high pepsin-to-protein ratio, it is only slightly degraded at pH 2.0 and
      conserved its immunoreactivity. Furthermore, Cry1Ab proteins were demonstrated to
      be stable in a more physiologically relevant in vitro digestibility test (pH 2.5,
      pepsin-to-substrate ratio 1:20 (w/w) with PC). Factors such as pH, SGF
      composition, and pepsin-to-substrate ratio then greatly influence the digestion
      of Cry1Ab proteins, confirming that new and more physiologically relevant in
      vitro digestibility tests should be also considered to study the relationship
      between the resistance of a protein to digestion and its allergenicity.

PMID- 20136084
TI  - Kinetics of the reactions of CH2Cl, CH3CHCl, and CH3CCl2 radicals with Cl2 in the
      temperature range 191-363 K.
AB  - The kinetics of three chlorinated free radical reactions with Cl(2) have been
      studied in direct time-resolved measurements. Radicals were produced in low
      initial concentrations by pulsed laser photolysis at 193 nm, and the subsequent
      decays of the radical concentrations were measured under pseudo-first-order
      conditions using photoionization mass spectrometer (PIMS). The bimolecular rate
      coefficients of the CH(3)CHCl + Cl(2) reaction obtained from the current
      measurements exhibit negative temperature dependence and can be expressed by the
      equation k(CH(3)CHCl + Cl(2)) = ((3.02 +/- 0.14) x 10(-12))(T/300 K)(-1.89+/
      0.19) cm(3) molecule(-1) s(-1) (1.7-5.4 Torr, 191-363 K). For the CH(3)CCl(2) +
      Cl(2) reaction the current results could be fitted with the equation
      k(CH(3)CCl(2) + Cl(2)) = ((1.23 +/- 0.02) x 10(-13))(T/300 K)(-0.26+/-0.10) cm(3)
      molecule(-1) s(-1) (3.9-5.1 Torr, 240-363 K). The measured rate coefficients for
      the CH(2)Cl + Cl(2) reaction plotted as a function of temperature show a minimum
      at about T = 240 K: first decreasing with increasing temperature and then, above
      the limit, increasing with temperature. The determined reaction rate coefficients
      can be expressed as k(CH(2)Cl + Cl(2)) = ((2.11 +/- 1.29) x 10(-14)) exp(773 +/-
      183 K/T)(T/300 K)(3.26+/-0.67) cm(3) molecule(-1) s(-1) (4.0-5.6 Torr, 201-363
      K). The rate coefficients for the CH(3)CCl(2) + Cl(2) and CH(2)Cl + Cl(2)
      reactions can be combined with previous results to obtain:
      k(combined)(CH(3)CCl(2) + Cl(2)) = ((4.72 +/- 1.66) x 10(-15)) exp(971 +/- 106
      K/T)(T/300 K)(3.07+/-0.23) cm(3) molecule(-1) s(-1) (3.1-7.4 Torr, 240-873 K) and
      k(combined)(CH(2)Cl + Cl(2)) = ((5.18 +/- 1.06) x 10(-14)) exp(525 +/- 63
      K/T)(T/300 K)(2.52+/-0.13) cm(3) molecule(-1) s(-1) (1.8-5.6 Torr, 201-873 K).
      All the uncertainties given refer only to the 1sigma statistical uncertainties
      obtained from the fitting, and the estimated overall uncertainty in the
      determined bimolecular rate coefficients is about +/-15%.

PMID- 20136085
TI  - Exothermic rate restrictions in long-range photoinduced charge separations in
      rigid media.
AB  - Glycerol/methanol (9:1) mixtures at 255 K behave as rigid media for photoinduced
      electron transfers that take place within a few hundred nanoseconds. This media
      also provides enough polarity and plasticity to accommodate charge separations
      with reaction free energies ranging from +3 to -34 kcal/mol. The distance
      dependence of the electron transfer rates from electronically excited aromatic
      hydrocarbons to nitriles in this medium is accurately described by an exponential
      decay constant of 1.65 per angstrom. These photoinduced electron transfers
      display, for the first time in charge separations between independent electron
      donors and acceptors, a free-energy relationship with a maximum rate followed by
      a decrease in the rate for more exothermic reactions. According to this free
      energy relationship, Franck-Condon factors are maximized at DeltaG(0)
      approximately -15 kcal/mol. It is suggested that the inverted region observed for
      these first-order photoinduced charge separations originates from a slower
      increase of their reorganization energies with DeltaG(0) than that of the
      analogous second-order photoinduced charge separations, for which inverted
      regions have never been clearly observed.

PMID- 20136086
TI  - Tetrakis(dimethylamino)ethylene chemiluminescence (TDE CL) characterization of
      the CMC and the viscosity of reversed microemulsions.
AB  - A new technique for the characterization of reversed microemulsions based on
      tetrakis(dimethylamino)ethylene (TDE) chemiluminescence (CL) has been explored.
      This method is based on the transport of quenching species from the continuous
      nonpolar phase to the interior of micelles. The emission intensity of TDE
      chemiluminescence was measured as a function of time for different concentrations
      of surfactant. These data were fit as an exponential decay, and the decay
      constant, k, was found. When k was plotted as a function of surfactant
      concentration, there was a clear change in the trend with surfactant
      concentration at a certain concentration; the concentration where this change
      occurred was concluded to be the critical micelle concentration (CMC). Using this
      method, the CMC of doctyl sulfosuccinate sodium salt (AOT) was evaluated in short
      chain alkanes (including n-dodecane, n-decane, n-octane, n-heptane, and
      isooctane), cyclohexane, and mineral oil (light), while the CMCs of sodium
      dodecylbenzenesulfonate (NaDDBs) and Triton X-100 (X-100) were detected in
      cyclohexane. The CMC values were found to range from 0.61 to 2.10 mM, and they
      decreased with the carbon chain length of the alkane solvent. In addition, it was
      found that the emission intensity of TDE chemiluminescence is sensitive to
      variations in solvent viscosity. TDE CL is suggested as a fluorescent molecular
      rotor for measuring the viscosity of the system which is nanosized.

PMID- 20136087
TI  - Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon
      cancer HT29 cells by inhibiting matrix metalloproteinase-2/-9 and urokinase
      plasminogen (uPA) through PKC and MAPK signaling pathway.
AB  - Benzyl isothiocyanate (BITC), a component of dietary cruciferous vegetables, has
      antioxidant and anticancer properties. In this study, we show for the first time
      the antimetastatic effects of BITC in human colon cancer HT29 cells. BITC had an
      inhibitory effect on cell migration and invasion. Protein levels of matrix
      metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase
      plasminogen activator (u-PA) were reduced by BITC in a concentration-dependent
      manner. BITC also exerted an inhibitory effect on phosphorylation of c-Jun N
      terminal kinase 1 and 2 (JNK1/2), extracellular signal-regulated kinases 1 and 2
      (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) that
      are upstream of nuclear factor kappa B (NF-kappaB). BITC inhibited DNA binding
      activity of NF-kappaB. Moreover, BITC decreased the levels of c-Fos, c-Jun, Ras,
      FAK, PI3K and GRB2 in HT29 cells. Reductions in the enzyme activity, protein and
      mRNA (mRNA) levels of MMP-2 were observed in BITC-treated HT29 cells. BITC also
      inhibited mRNA levels of MMP-2, -7, and -9 in HT29 cells. Results from zymography
      showed that BITC treatment decreased MMP-2 expression in a concentration
      dependent manner. BITC inhibited PKCdelta activity in HT29 cells. Furthermore,
      inhibitors specific for JNK (SP600125) reduced expression of MMP-2, MMP-9, and u
      PA. These results demonstrated that BITC could alter HT29 cell metastasis by
      reduction of MMP-2, MMP-9, and u-PA expression through the suppression of a PKC,
      MAPK signaling pathway and inhibition of NF-kappaB levels. These findings suggest
      that BITC has potential as an antimetastatic agent.

PMID- 20136088
TI  - Atmospherically stable nanoscale zero-valent iron particles formed under
      controlled air contact: characteristics and reactivity.
AB  - Atmospherically stable NZVI (nanoscale zero-valent iron) particles were produced
      by modifying shell layers of Fe(H2) NZVI particles (RNIP-10DS) by using a
      controlled air contact method. Shell-modified NZVI particles were resistant to
      rapid aerial oxidation and were shown to have TCE degradation rate constants that
      were equivalent to 78% of those of pristine NZVI particles. Fe(H2) NZVI particles
      that were vigorously contacted with air (rapidly oxidized) showed a substantially
      compromised reactivity. Aging of shell-modified particles in water for one day
      resulted in a rate increase of 54%, implying that depassivation of the shell
      would play an important role in enhancing reactivity. Aging of shell-modified
      particles in air led to rate decreases by 14% and 46% in cases of one week and
      two months of aging, respectively. A series of instrumental analyses using
      transmission electron microscopy, X-ray diffractography, X-ray photoelectron
      spectroscopy, and X-ray absorption near-edge structure showed that the shells of
      modified NZVI particles primarily consisted of magnetite (Fe(3)O(4)). Analyses
      also implied that the new magnetite layer produced during shell modification was
      protective against shell passivation. Aging of shell-modified particles in water
      yielded another major mineral phase, goethite (alpha-FeOOH), whereas aging in air
      produced additional shell phases such as wustite (FeO), hematite (alpha
      Fe(2)O(3)), and maghemite (gamma-Fe(2)O(3)).

PMID- 20136089
TI  - Immobilized redox mediators on anion exchange resins and their role on the
      reductive decolorization of azo dyes.
AB  - Quinoid redox mediators (RM), including 1,2-naphthoquinone-4-sulfonate (NQS) and
      anthraquinone-2,6-disulfonate (AQDS), were adsorbed on anion exchange resins
      (AER) in order to explore their catalytic effects on the reductive decolorization
      of azo dyes by anaerobic granular sludge. Immobilized quinones preserved their
      catalytic properties once adsorbed on the surface of AER. Addition of different
      concentrations of immobilized quinones to sludge incubations increased up to 8.8
      fold the rate of decolorization of azo dyes compared to controls lacking
      quinones. The catalytic effects of immobilized quinones also resulted in a
      greater extent of decolorization in quinone-amended incubations compared to
      controls lacking external RM. Spectrophotometric screening did not show any
      detachment of either AQDS or NQS during decolorization assays confirming that the
      enhanced decolorization accomplished was exclusively attributed to quinones
      immobilized on AER. Sterile controls including the maximum concentration of
      immobilized quinones supplied (4.8 mM) did not show any removal of azo dyes
      suggesting that physical-chemical processes, such as adsorption or chemical
      reduction, were not responsible for the enhanced decolorization reached. To our
      knowledge, this is the first study demonstrating the catalytic contribution of RM
      immobilized on AER on the reductive (bio)transformation of azo dyes.

PMID- 20136090
TI  - Nanostructured multifunctional electromagnetic materials from the guest-host
      inorganic-organic hybrid ternary system of a polyaniline-clay-polyhydroxy iron
      composite: preparation and properties.
AB  - A nanostructured electromagnetic polyaniline-polyhydroxy iron-clay composite
      (PPIC) was prepared by oxidative radical emulsion polymerization of aniline in
      the presence of polyhydroxy iron cation (PIC) intercalated clays. Morphological
      observation through SEM, TEM, and AFM suggested the formation of self-assembled
      nanospheres of PIC with self-assembled PANI engulfed over PIC, and the presence
      of iron in PPIC was confirmed by the EDS analysis. XRD studies revealed that PPIC
      are comprised of exfoliated clay layers with PIC in the distorted spinel
      structure. Magnetic property measurements showed that saturation magnetization
      increased from 7.3 x 10(-3) to 2.5 emu/g upon varying the amount of PHIC content
      from 0 to 10%. Electrical conductivity measurements with the same composition
      were observed to be in the range of 3.0 x 10(-2) to 1.1 S/cm. Thermal stability
      studies using TGA in combination with DTG suggested that PPICs were thermally
      stable up to 350 degrees C. The interaction among clay layers, PIC, and PANI
      chains in PPIC were manifested from the studies made by FTIR and DSC analysis.
      The prospects for the direct application of this material are developing low-cost
      chemical sensors and also processable electromagnetic interference shielding
      materials for high technological applications.

PMID- 20136091
TI  - Powder crystallography by combined crystal structure prediction and high
      resolution 1H solid-state NMR spectroscopy.
AB  - A fast method for crystal structure determination using crystal structure
      prediction and solid-state (1)H NMR is presented. This technique does not need
      any prior knowledge except the chemical formula; resonance assignment is not
      necessary. Starting from an ensemble of predicted crystal structures for powdered
      thymol, comparison between experimental and calculated (1)H solid-state isotropic
      NMR chemical shifts is sufficient to determine which predicted structure
      corresponds to the powder under study. The same approach using proton-proton spin
      diffusion data is successful and can be used for cross-validation.

PMID- 20136092
TI  - Study of the soret effect in monosaccharide solutions.
AB  - We investigated the thermal diffusion behavior of aqueous solutions of
      monosaccharides with the infrared thermal diffusion forced Rayleigh scattering
      (IR-TDFRS) setup. As monosaccharides, we studied the three aldohexoses glucose,
      galactose, and mannose and the two ketohexoses sorbose and fructose. All sugars
      have the same molecular weight, but their structures differ as well as some
      physical properties such as viscosity, density, thermal expansion coefficient,
      and optical rotation. Additionally, we measured the viscosity and the optical
      rotation of the monosaccharide solutions in the investigated temperature and
      concentration range. While there is a clear correlation between the structure and
      the thermal diffusion behavior for alkanes, the situation is much more
      complicated for the monosaccharides. Nevertheless, as in the case of the alkanes,
      we find a correlation between the thermal diffusion coefficient with the ratio of
      the thermal expansion coefficient and the kinematic viscosity. We discuss the
      physical principles, which connect the thermal diffusion behavior with other
      thermophysical properties and the structure of the different sugars.

PMID- 20136093
TI  - Quantitative turbidimetric assay of enzymatic gram-negative bacteria lysis.
AB  - In this Technical Note, the quantitative turbidimetric assay for determination of
      the bacteriolytic activity of enzymes with gram-negative bacteria is proposed.
      The reactivity of hen white-egg lysozyme toward gram-negative E. coli intact
      cells was studied. It was found that the highest lysis rate occurred at pH 8.9 in
      the system containing 0.03 M NaCl. The mechanism of the reaction is discussed and
      applied for the quantitative evaluation of the reaction rate. The proposed method
      enables fast, reliable, and reproducible analysis of bacteriolytic activity of
      lysozyme with gram-negative bacteria.

PMID- 20136094
TI  - Approaching the complexity of elastase-digested membrane proteomes using off-gel
      IEF/nLC-MALDI-MS/MS.
AB  - Liquid chromatography, coupled with tandem mass spectrometry, is an established
      method for the identification of proteins from a complex sample. Despite its wide
      application, the analysis of whole proteomes still represents a challenge to
      researchers, because of the complexity and dynamic range of protein
      concentrations in biological samples. The analysis of such samples can be
      improved by adding a prefractionation step or a combination of orthogonal
      separation techniques. Off-gel isoelectric focusing (OGE) has successfully been
      used for prefractionation of a tryptic digest prior to nLC separation. In
      contrast to previous published results, we present a complete glycerol-free OGE
      for the analysis of purple membranes and Corynebacterium glutamicum membranes
      using the less-specific enzyme elastase. More than 85% of the identified unique
      peptides were found in solely one fraction, with very little carryover. These
      results are in accordance with those published for tryptic peptides. Therefore,
      OGE can be used as an effective prefractionation method in a multidimensional
      separation experiment of nontryptic membrane peptides.

PMID- 20136095
TI  - Reactions of a phosphinoaldehyde with Pd(II), Rh(I), and Ir(I) precursors,
      including the formation of complexes containing a P,OH-chelated
      phosphinohemiacetal ligand: a new bonding mode.
AB  - The complexes trans-PdCl(2)[eta(1)-P-(Ph(2)P)CH(Ph)CH(Me)CH(OMe)(2)](2) (1) and
      M(H)Cl[eta(2)-P,OH-(Ph(2)P)CH(Ph)CH(Me)CH(OH)OMe][eta(2)-P,C(O)
      (Ph(2)P)CH(Ph)CH(Me)C(O)], M = Rh (3) and Ir (4), are synthesized by reacting the
      phosphinoaldehyde [3-(diphenylphosphino)-3-phenyl-2-methyl]propionaldehyde
      [(Ph(2)P)(2)CH(Ph)CH(Me)CHO] with trans-PdCl(2)(PhCN)(2), [RhCl(COD)](2), and
      [IrCl(COD)](2), respectively, in MeOH; trans-PdCl(2)[eta(1)-P
      (Ph(2)P)CH(Ph)CH(Me)CHO](2) (2) is isolated from the same reaction in CH(2)Cl(2).
      One diastereomer of each of the complexes 1, 3 x MeOH, and 4 x MeOH was
      characterized by X-ray analysis. The stereochemistry of such complexes in the
      solid state and in solution (MeOH and CH(2)Cl(2)) is discussed. In CD(2)Cl(2),
      NMR data suggest that the coordinated hemiacetal moiety of 3 (but not 4)
      undergoes reversible loss of MeOH; this process is associated with equilibria
      between various diastereomers of 3 that were investigated by (31)P{(1)H},
      (13)C{(1)H}, (1)H, (1)H{(31)P}, and HSQC and HMBC (1)H/(31)P{(1)H} and
      (1)H/(13)C{(1)H} NMR spectroscopies. Complexes 3 and 4 reveal a new chelate
      bonding mode via a P atom and the hydroxyl O atom of a hemiacetal. Solvent
      dependent stereochemical changes within solution species imply that such chiral
      phosphinoaldehydes are not likely to be useful ligands for applications in
      asymmetric catalysis, although conditions are suggested for testing the complexes
      as potential precursors for nonasymmetric catalytic processes.

PMID- 20136096
TI  - Site-specific incorporation of fluorotyrosines into proteins in Escherichia coli
      by photochemical disguise.
AB  - Fluorinated analogues of tyrosine can be used to manipulate the electronic
      environments of protein active sites. The ability to selectively mutate tyrosine
      residues to fluorotyrosines is limited, however, and can currently only be
      achieved through the total synthesis of proteins. As a general solution to this
      problem, we genetically encoded the unnatural amino acids o-nitrobenzyl-2
      fluorotyrosine, -3-fluorotyrosine, and -2,6-difluorotyrosine in Escherichia coli.
      These amino acids are disguised from recognition by the endogenous protein
      biosynthetic machinery, effectively preventing global incorporation of
      fluorotyrosine into proteins.

PMID- 20136097
TI  - Identification and functional characterization of a novel acetylcholine-binding
      protein from the marine annelid Capitella teleta.
AB  - We identified a homologue of the molluscan acetylcholine-binding protein (AChBP)
      in the marine polychaete Capitella teleta, from the annelid phylum. The amino
      acid sequence of C. teleta AChBP (ct-AChBP) is 21-30% identical with those of
      known molluscan AChBPs. Sequence alignments indicate that ct-AChBP has a
      shortened Cys loop compared to other Cys loop receptors, and a variation on a
      conserved Cys loop triad, which is associated with ligand binding in other AChBPs
      and nicotinic ACh receptor (nAChR) alpha subunits. Within the D loop of ct-AChBP,
      a conserved aromatic residue (Tyr or Trp) in nAChRs and molluscan AChBPs, which
      has been implicated directly in ligand binding, is substituted with an
      isoleucine. Mass spectrometry results indicate that Asn122 and Asn216 of ct-AChBP
      are glycosylated when expressed using HEK293 cells. Small-angle X-ray scattering
      data suggest that the overall shape of ct-AChBP in the apo or unliganded state is
      similar to that of homologues with known pentameric crystal structures. NMR
      experiments show that acetylcholine, nicotine, and alpha-bungarotoxin bind to ct
      AChBP with high affinity, with K(D) values of 28.7 microM, 209 nM, and 110 nM,
      respectively. Choline bound with a lower affinity (K(D) = 163 microM). Our
      finding of a functional AChBP in a marine annelid demonstrates that AChBPs may
      exhibit variations in hallmark motifs such as ligand-binding residues and Cys
      loop length and shows conclusively that this neurotransmitter binding protein is
      not limited to the phylum Mollusca.

PMID- 20136098
TI  - Graphene and nanowire transistors for cellular interfaces and electrical
      recording.
AB  - Nanowire field-effect transistors (NW-FETs) have been shown to be powerful
      building blocks for nanoscale bioelectronic interfaces with cells and tissue due
      to their excellent sensitivity and their capability to form strongly coupled
      interfaces with cell membranes. Graphene has also been shown to be an attractive
      building block for nanoscale electronic devices, although little is known about
      its interfaces with cells and tissue. Here we report the first studies of
      graphene field effect transistors (Gra-FETs) as well as combined Gra- and NW-FETs
      interfaced to electrogenic cells. Gra-FET conductance signals recorded from
      spontaneously beating embryonic chicken cardiomyocytes yield well-defined
      extracellular signals with signal-to-noise ratio routinely >4. The conductance
      signal amplitude was tuned by varying the Gra-FET working region through changes
      in water gate potential, V(wg). Signals recorded from cardiomyocytes for
      different V(wg) result in constant calibrated extracellular voltage, indicating a
      robust graphene/cell interface. Significantly, variations in V(wg) across the
      Dirac point demonstrate the expected signal polarity flip, thus allowing, for the
      first time, both n- and p-type recording to be achieved from the same Gra-FET
      simply by offsetting V(wg). In addition, comparisons of peak-to-peak recorded
      signal widths made as a function of Gra-FET device sizes and versus NW-FETs
      allowed an assessment of relative resolution in extracellular recording.
      Specifically, peak-to-peak widths increased with the area of Gra-FET devices,
      indicating an averaged signal from different points across the outer membrane of
      the beating cells. One-dimensional silicon NW- FETs incorporated side by side
      with the two-dimensional Gra-FET devices further highlighted limits in both
      temporal resolution and multiplexed measurements from the same cell for the
      different types of devices. The distinct and complementary capabilities of Gra-
      and NW-FETs could open up unique opportunities in the field of bioelectronics in
      the future.

PMID- 20136099
TI  - Solution structure of an acyl carrier protein domain from a fungal type I
      polyketide synthase.
AB  - Acyl (peptidyl) carrier protein (ACP or PCP) is a crucial component involved in
      the transfer of thiol ester-bound intermediates during the biosynthesis of
      primary and secondary metabolites such as fatty acids, polyketides, and
      nonribosomal peptides. Although many carrier protein three-dimensional structures
      have been determined, to date there is no model available for a fungal type I
      polyketide synthase ACP. Here we report the solution structure of the
      norsolorinic acid synthase (NSAS) holo ACP domain that has been excised from the
      full-length multifunctional enzyme. NSAS ACP shows similarities in three
      dimensional structure with other type I and type II ACPs, consisting of a four
      helix bundle with helices I, II, and IV arranged in parallel. The N-terminus of
      helix III, however, is unusually hydrophobic, and Phe1768 and Leu1770 pack well
      with the core of the protein. The result is that unlike other carrier proteins,
      helix III lies almost perpendicular to the three major helices. Helix III is well
      defined by numerous NMR-derived distance restraints and may be less flexible than
      counterparts in type II FAS and PKS ACPs. When the holo ACP is derivatized with a
      hexanoyl group, only minor changes are observed between the HSQC spectra of the
      two ACP species and no NOEs are observed for this hydrophobic acyl group. Along
      with the mammalian type I FAS, this further strengthens the view that type I ACPs
      do not show any significant affinity for hydrophobic (nonpolar) chain assembly
      intermediates attached via the 4'-phosphopantetheine prosthetic group.

PMID- 20136100
TI  - Synthesis of heteroatom substituted naphthoporphyrazine derivatives with near
      infrared absorption and emission.
AB  - In an effort to develop effective new optical contrast agents, we report the
      synthesis of porphyrazines (pzs) of the form H(2)[pz(A(4-n);C(n))], n = 1, and 2
      (trans-), where "A" represents peripheral heteroatom (S- and O-) R-groups and "C"
      is a fused, beta,beta'-diisopropyloxynaphtho group. The sulfide appended trans
      H(2)[pz(A(2);C(2))] pz (7) has the longest wavelength absorption, approximately
      874 nm (log epsilon = 4.53), and S(1) fluorescence at approximately 927 nm,
      wavelengths within the window of maximum tissue penetration. Emission from the
      oxygen-atom appended naphtho-pzs (8, 9) has been observed within carcinoma cells,
      confirming cellular uptake and their potential use as optical agents.

PMID- 20136101
TI  - Intramolecular double proton transfer from 2-hydroxy-2-iminoacetic acid to 2
      amino-2-oxoacetic acid.
AB  - The double intramolecular proton transfer process which transforms 2-hydroxy-2
      iminoacetic acid into 2-amino-2-oxoacetic acid is analyzed. The MP2 and DFT
      calculations were performed for different tautomers and conformers of these
      species. Pople style (6-311++G(d,p), 6-311++G(3df,3pd)) and Dunning type (aug-cc
      pVTZ) basis sets were applied. O-H...O, N-H...O, and O-H...N intramolecular
      hydrogen bonds were also analyzed with the use of Quantum Theory of "Atoms in
      Molecules" (QTAIM) as well as Natural Bond Orbitals (NBO) method. Different
      criteria of the hydrogen bonding existence were applied here for intramolecular
      interactions. It was found that some of N-H...O hydrogen bonds may be treated as
      blue-shifting ones.

PMID- 20136102
TI  - Chiral bifunctional thiourea-catalyzed enantioselective Michael addition of
      ketones to nitrodienes.
AB  - Simple bifunctional thioureas, derived from the commercially available
      saccharides and chiral diamines, have been shown tunably to promote Michael-type
      addition of ketones to alpha,beta-gamma,delta-nitrodienes. The Michael adducts
      were obtained in good yields albeit with high enantioselectivites (84-99% ee).
      Furthermore, these products can be readily transformed into more useful
      molecules.

PMID- 20136103
TI  - Cracking of drying latex films: an ESEM experiment.
AB  - In this study environmental scanning electron microscopy was used to observe the
      cracking of drying latex films below their glass-transition temperature. By
      controlling the relative humidity so that it decreases linearly with time, a
      critical level of humidity at which cracking occurs can be determined and this is
      measured as a function of film thickness. It was found that the cracking humidity
      decreases with increases in film thickness for thicknesses in the range of 30 to
      100 mum and then remains almost unchanged. A scaling argument can be used to fit
      the data very well and indicates that cracking occurs as soon as the entire film
      is consolidated into close packing.

PMID- 20136104
TI  - Excited-state intramolecular hydrogen atom transfer of curcumin in surfactant
      micelles.
AB  - Femtosecond fluorescence upconversion experiments were performed on the naturally
      occurring medicinal pigment, curcumin, in anionic, cationic, and neutral
      micelles. In our studies, the micelles are composed of sodium dodecyl sulfate
      (SDS), dodecyl trimethyl ammonium bromide (DTAB), and triton X-100 (TX-100). We
      demonstrate that the excited-state kinetics of curcumin in micelles have a fast
      (3-8 ps) and slow (50-80 ps) component. While deuteration of curcumin has a
      negligible effect on the fast component, the slow component exhibits a pronounced
      isotope effect of approximately 1.6, indicating that micelle-captured curcumin
      undergoes excited-state intramolecular hydrogen atom transfer. Studies of
      solvation dynamics of curcumin in a 10 ps time window reveal a fast component (<
      or = 300 fs) followed by a 8, 6, and 3 ps component in the solvation correlation
      function for the TX-100, DTAB, and SDS micelles, respectively.

PMID- 20136105
TI  - Interaction studies of coumaroyltyramine with human serum albumin and its
      biological importance.
AB  - N-trans-p-coumaroyltyramine (CT) isolated from Physalis minima is a phenolic
      substance exhibiting many pharmacological activities like potent inhibition of
      acetyl cholinesterase, cell proliferation, platelet aggregation, and also
      antioxidant activity. Here, we have studied the binding of CT with HSA at
      physiological pH 7.2 by using fluorescence, circular dichroism spectroscopy, mass
      spectrometry, and molecular docking methods. From the fluorescence emission
      studies, the number of binding sites and binding constant were calculated to be 2
      and (4.5 +/- 0.01) x 10(5) M(-1), respectively. The free energy change was
      calculated as -7.6 kcal M(-1) at 25 degrees C, which indicates the hydrophobic
      interactions of CT with HSA and is in well agreement with the computational
      calculations and molecular docking studies. The changes in the secondary
      structure of HSA after its complexation with the ligand were studied with CD
      spectroscopy, which indicated that the protein became partially unfolded. Also,
      temperature did not affect the HSA-CT complexes. The binding of CT with HSA was
      detected as 2 molecules bound to HSA was determined using micro TOF-Q mass
      spectrometry. Further, molecular docking studies revealed that CT was binding at
      subdomain IIA with hydrophobic interactions and also by hydrogen-bond
      interactions between the hydroxyl (OH) group of carbon-16 and carbon-2 of CT and
      Arg222, Ala291, Val293, and Met298 of HSA, with hydrogen-bond distances of 2.488,
      2.811, 2.678, and 2.586 A, respectively.

PMID- 20136106
TI  - Molecular dynamics simulation of surfactin derivatives at the decane/water
      interface at low surface coverage.
AB  - Interfacial behavior of surfactin methyl ester derivatives at the n-decane/water
      interface at low surface coverage has been studied by molecular dynamics
      simulation. Molecular orientations, structural variability of the peptide ring
      backbones, interfacial molecular areas, and the motion activities of surfactin
      derivatives have been determined. The simulations show that surfactin monomethyl
      ester stands vertically at the oil/water interface compared with surfactin
      molecule. The aliphatic chains tilt at the interface and can fold back to
      interact with the hydrophobic amino acid residues within the same molecule. Amino
      acid residues that the aliphatic chains are favorable to interact with are
      different between surfactin derivatives. The peptide ring backbones of surfactin
      and surfactin derivatives expand at the interface. Interfacial molecular areas of
      surfactin derivatives are all about 110 A(2). Translational and rotational
      motions of surfactin derivatives are limited at the interface, and the motion
      activities increase with the hydrophobic character of the peptide moiety.

PMID- 20136107
TI  - Hollow polymer particles with nanoscale pores and reactive groups on their rigid
      shells: preparation and application as nanoreactors.
AB  - A novel type of hollow polymeric particles was prepared according to a strategy
      consisting of three major steps: the synthesis of template particles (PMV) based
      on maleic anhydride/vinyl acetate; the formation of core/shell particles by using
      maleic anhydride/divinylbenzene as comonomers, AIBN as initiator, and PMV as
      templates; and the removal of the core by dissolving it with an organic solvent.
      This route gave rise to core/shell and hollow particles in high yields, and the
      as-prepared particles possessed obvious advantages. The size of the core and the
      thickness of the shell were controllable by adjusting the reaction conditions.
      The shells were of high rigidity and strength as a result of the high cross
      linking degree. The surface anhydride groups offered a platform for various
      postfunctionalization reactions of the particles. The nanoscale pores in the
      shells enabled an encapsulation of target compounds. The as-prepared hollow
      particles could be applied as "nanoreactors". To attest to this concept, Ag
      encapsulated composite particles were further prepared via redox reactions
      between NaBH(4) and AgNO(3) inside the hollow particles. A mechanism for the
      formation of core/shell particles and pores in the shells is proposed.

PMID- 20136108
TI  - Low-temperature FTIR study of multiple K intermediates in the photocycles of
      bacteriorhodopsin and xanthorhodopsin.
AB  - Low-temperature FTIR spectroscopy of bacteriorhodopsin and xanthorhodopsin was
      used to elucidate the number of K-like bathochromic states, their sequence, and
      their contributions to the photoequilibrium mixtures created by illumination at
      80-180 K. We conclude that in bacteriorhodopsin the photocycle includes three
      distinct K-like states in the sequence bR (hv)--> I* --> J --> K(0) --> K(E) -->
      L --> ..., and similarly in xanthorhodopsin. K(0) is the main fraction in the
      mixture at 77 K that is formed from J. K(0) becomes thermally unstable above
      approximately 50 K in both proteins. At 77 K, both J-to-K(0) and K(0)-to-K(E)
      transitions occur and, contrarily to long-standing belief, cryogenic trapping at
      77 K does not produce a pure K state but a mixture of the two states, K(0) and
      K(E), with contributions from K(E) of approximately 15 and approximately 10% in
      the two retinal proteins, respectively. Raising the temperature leads to
      increasing conversion of K(0) to K(E), and the two states coexist (without
      contamination from non-K-like states) in the 80-140 K range in bacteriorhodopsin,
      and in the 80-190 K range in xanthorhodopsin. Temperature perturbation
      experiments in these regions of coexistence revealed that, in spite of the
      observation of apparently stable mixtures of K(0) and K(E), the two states are
      not in thermally controlled equilibrium. The K(0)-to-K(E) transition is
      unidirectional, and the partial transformation to K(E) is due to distributed
      kinetics, which governs the photocycle dynamics at temperatures below
      approximately 245 K (Dioumaev and Lanyi, Biochemistry 2008, 47, 11125-11133).
      From spectral deconvolution, we conclude that the K(E) state, which is
      increasingly present at higher temperatures, is the same intermediate that is
      detected by time-resolved FTIR prior to its decay, on a time scale of hundreds of
      nanoseconds at ambient temperature (Dioumaev and Braiman, J. Phys. Chem. B 1997,
      101, 1655-1662), into the K(L) state. We were unable to trap the latter
      separately from K(E) at low temperature, due to the slow distributed kinetics and
      the increasingly faster overlapping formation of the L state. Formation of the
      two consecutive K-like states in both proteins is accompanied by distortion of
      two different weakly bound water molecules: one in K(0), the other in K(E). The
      first, well-documented in bacteriorhodopsin at 77 K where K(0) dominates, was
      assigned to water 401 in bacteriorhodopsin. The other water molecule, whose
      participation has not been described previously, is disturbed on the next step of
      the photocycle, in K(E), in both proteins. In bacteriorhodopsin, the most likely
      candidate is water 407. However, unlike bacteriorhodopsin, the crystal structure
      of xanthorhodopsin lacks homologous weakly bound water molecules.

PMID- 20136109
TI  - Probing the interaction of 1-ethyl-3-methylimidazolium ethyl sulfate
      ([Emim][EtSO4]) with alcohols and water by solvent and rotational relaxation.
AB  - The effect of the addition of cosolvents in the room temperature ionic liquid
      (RTIL) 1-ethyl-3-methylimidazolium ethyl sulfate ([Emim][EtSO(4)]) was probed by
      the solvent and rotational relaxation studies of coumarin 153 in neat ionic
      liquid [Emim][EtSO(4)] and [Emim][EtSO(4)]-cosolvent mixtures by using steady
      state and time-resolved fluorescence spectroscopy. With gradual addition of
      cosolvents in the RTIL, both the average solvation time and rotational relaxation
      times gradually decrease. Addition of cosolvents in the IL decreases the
      viscosity of the medium. We have optimized the geometry of [Emim][EtSO(4)] and
      [Emim][EtSO(4)]-cosolvent mixtures by using quantum chemical calculations using
      density functional theory methods, which show the formation of hydrogen bond
      between cosolvents with [Emim][EtSO(4)]. With addition of the same amount of
      alcohols in neat [Emim][EtSO(4)], the rotational relaxation time decreases more
      compared to the addition of the same amount of water.

PMID- 20136110
TI  - Nature of molecular rotation in supercooled glycerol under nanoconfinement.
AB  - The dynamics of glass-forming liquids under nanoconfinement is key to
      understanding a variety of phenomena in nature and modern technology. We report a
      (13)C NMR spectroscopic study that directly demonstrates that alpha-relaxation in
      bulk glycerol involves an isotropic rotational jump of the constituent molecules.
      The activation energy of this motion is approximately 78 kJ mol(-1) in the bulk,
      which abruptly changes to a low value of approximately 27.5 kJ mol(-1),
      characteristic of beta-processes, upon confinement of glycerol into approximately
      2 nm pores in mesoporous silica. This observation implies that the molecular
      dynamics associated with structural relaxation near glass transition are
      inherently different in supercooled glycerol in the bulk and under extreme
      nanoconfinement.

PMID- 20136111
TI  - Good solvent effects of C70 cluster formations and their electron-transporting
      and photoelectrochemical properties.
AB  - Good solvent effects of C(70) cluster formations and their electron-transporting
      and photoelectrochemical properties have been systematically examined for the
      first time. Nano-to-micrometer scale assemblies of C(70) with different
      morphologies were prepared by rapidly injecting poor solvent (i.e., acetonitrile)
      into a solution of C(70) dissolved in various good solvents (i.e., benzene,
      toluene, chlorobenzene, etc). The cluster morphology engineering was successfully
      achieved by changing the good solvent, yielding the spherical, rodlike, or
      platelike clusters in the mixed solvents. The clusters of C(70) were
      electrophoretically deposited onto a nanostructured SnO(2) electrode to examine
      the photoelectrochemical properties under the white light or monochromatic light
      illumination. The maximum incident photon-to-current efficiency (IPCE) varied
      from 0.8 to 10% depending on the combinations of the poor-good solvents. The
      differences in the IPCE values are discussed in terms of the surface area,
      thickness, and electron mobility of the deposited cluster films. The electron
      mobility is found to be the most predominant factor for the IPCE, indicating the
      importance of the electron-transporting process in the overall photocurrent
      generation. In addition, the electron mobility is closely correlated with the
      underlying molecular alignment and the resultant cluster structure. Thus, these
      results will provide basic clue for the design of C(70)-based molecular devices
      including the organic photovoltaics.

PMID- 20136112
TI  - Free energy profile of the interaction between a monomer or a dimer of protegrin
      1 in a specific binding orientation and a model lipid bilayer.
AB  - The free energies of adsorption of the monomer or dimer of the cationic beta
      hairpin antimicrobial peptide protegrin-1 (PG1) in a specific binding orientation
      on a lipid bilayer are determined using molecular dynamics (MD) simulations and
      Poisson-Boltzmann calculations. The bilayer is composed of anionic palmitoyl
      oleoyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine
      (POPE) with ratio 1:3 (POPG/POPE). PG1 is believed to kill bacteria by binding on
      their membranes. There, it forms pores that lyse the bacteria. Herein we focus on
      the thermodynamics of binding. In particular, we explore the role of counterion
      release from the lipid bilayer upon adsorption of either the monomeric or the
      dimeric form of PG1. Twenty-two 4-ns-long MD trajectories of equilibrated systems
      are generated to determine the free energy profiles for the monomer and dimer as
      a function of the distance between the peptide(s) and the membrane surface. The
      MD simulations are conducted at 11 different separations from the membrane for
      each of the two systems, one with PG1, the second with a PG1 dimer of only a
      specific orientation of the monomer and dimer without taking into account the
      change of entropy for the peptide. To calculate the potential of mean force for
      each peptide/membrane system, a variant of constrained MD and thermodynamic
      integration is used. We observed that PG1 dimer binds more favorably to the
      POPG/POPE membrane. A simple method for relating the free energy profile to the
      PG1-membrane binding constant is employed to predict a free energy of adsorption
      of -2.4 +/- 0.8 kcal/mol. A corresponding PG1-dimer-membrane binding constant is
      calculated as -3.5 +/- 1.1 kcal/mol. Free energy profiles from MD simulation were
      extensively analyzed and compared with results of Poisson-Boltzmann theory. We
      find the peptide-membrane attraction to be dominated by the entropy increase due
      to the release of counterions in a POPG/POPE lipid bilayer.

PMID- 20136113
TI  - Kinetics and equilibria of cis/trans isomerization of secondary amide peptide
      bonds in linear and cyclic peptides.
AB  - The secondary amide peptide bonds that comprise up to one-third of the bonds of
      peptide or protein backbones can exist as cis and trans isomers, with the trans
      isomer being highly favored. However, there is little quantitative data on the
      kinetics and equilibria of cis-trans isomerization of secondary amide peptide
      bonds due to the difficulty of detecting the very small population of cis
      isomers. Knowledge of factors that influence the kinetics and equilibria of cis
      trans isomerization of secondary amide peptide bonds will contribute to a more
      complete understanding of the structural and dynamic behavior of the backbones of
      peptides and unfolded proteins and of complex protein folding kinetics. We have
      characterized the kinetics and equilibria of cis-trans isomerization of the Xaa
      Yaa secondary amide peptide bonds of the linear dithiol and cyclic disulfide
      forms of the peptides Ac-Cys-Xaa-Yaa-Cys-His-NH(2), where Xaa-Yaa is Ala-Phe, Phe
      Ala, Ala-Tyr, and Tyr-Ala, by (1)H NMR. Resolved resonances were observed for the
      Ala-methyl protons of the trans and the much less abundant cis isomers due to
      differential shielding of the Ala-methyl protons of the trans and cis isomers by
      ring current effects from the Phe and Tyr side chains. The population of the cis
      isomers was determined from the relative intensities of the Ala-methyl resonances
      for the trans and cis isomers, and rate constants for cis-to-trans and trans-to
      cis isomerization were determined by the magnetization transfer NMR method. The
      population of the cis isomers ranges from 0.07 to 0.12%, and the rate constants
      indicate that, when there is a trans-to-cis interchange, it is rapidly followed
      by a cis-to-trans interchange back to the more stable trans conformation.
      Although cyclization by disulfide bond formation imposes conformational
      constraints on the peptide backbones, cyclization is found to have relatively
      small affects on the dynamics of cis-trans isomerization.

PMID- 20136114
TI  - Valence bond structures for three-electron three-center and four-electron three
      center bonding units: some further examples.
AB  - A formula is derived for the R-atom valence in the valence bond structure X.R:Y,
      with one overlapping atomic orbital per atomic center. Using this formula, the
      results of STO-6G valence bond calculations for linear H(3), HFH, FHF, and F(3)
      transition states show that for each molecule, the R-atom exhibits increased
      valence or electronic hypervalence, that is, its valence exceeds that for the
      Lewis structure X R:Y, with no one-electron bond. Consideration is also given to
      (a) valence bond formulations for the conversion of the excited states of the
      reactants into the excited states of the products for the X(*) + R:Y --> X:R +
      Y(*) and X(:(-)) + R:Y --> X:R + Y(:(-)) reactions and the state correlation
      diagram for X(*) + R:Y --> X:R + Y(*), (b) Kekule and Dewar increased-valence
      structures for D(6h) symmetry systems, and (c) the three-center molecular orbital
      interaction of the X(*) electron with the antibonding molecular orbital of R:Y,
      to form the one-electron X-R bond of X.R:Y.

PMID- 20136115
TI  - Quantitative laser diagnostic and modeling study of C2 and CH chemistry in
      combustion.
AB  - Quantitative concentration measurements of CH and C(2) have been performed in
      laminar, premixed, flat flames of propene and cyclopentene with varying
      stoichiometry. A combination of cavity ring-down (CRD) spectroscopy and laser
      induced fluorescence (LIF) was used to enable sensitive detection of these
      species with high spatial resolution. Previously, CH and C(2) chemistry had been
      studied, predominantly in methane flames, to understand potential correlations of
      their formation and consumption. For flames of larger hydrocarbon fuels, however,
      quantitative information on these small intermediates is scarce, especially under
      fuel-rich conditions. Also, the combustion chemistry of C(2) in particular has
      not been studied in detail, and although it has often been observed, its role in
      potential build-up reactions of higher hydrocarbon species is not well
      understood. The quantitative measurements performed here are the first to detect
      both species with good spatial resolution and high sensitivity in the same
      experiment in flames of C(3) and C(5) fuels. The experimental profiles were
      compared with results of combustion modeling to reveal details of the formation
      and consumption of these important combustion molecules, and the investigation
      was devoted to assist the further understanding of the role of C(2) and of its
      potential chemical interdependences with CH and other small radicals.

PMID- 20136116
TI  - First high resolution spectroscopic studies and ab initio calculations of
      ethanetellurol.
AB  - The millimeter-wave rotational spectrum of ethanetellurol has been recorded and
      assigned for the first time. The spectroscopic study has been complemented by
      high level ab initio calculations. Geometries, total electronic energies, and
      harmonic vibrational frequencies have been determined at the MP2 level. A small
      core relativistic pseudopotential basis set (cc-pVTZ-PP) was employed to describe
      the tellurium atom. Two stable conformers, synclinal and antiperiplanar, have
      been identified. Both theory and experiment have shown the synclinal form to be
      more stable by 2 kJ/mol. The doublet structure observed in the rotational
      spectrum of synclinal conformer is attributed to tunneling motion of tellurol
      functional group. The energy difference between 0(+) and 0(-) substates split by
      tunneling has been determined from the observed spectra.

PMID- 20136117
TI  - Total synthesis and determination of the absolute configuration of (-)-idesolide.
AB  - The first total synthesis of (-)-idesolide was achieved via organocatalytic,
      enantioselective oxidative kinetic resolution (OKR) using (1S,4S)-4-Bn-1-Bu
      AZADOH- and AZADO-catalyzed dimerization of (S)-(-)-methyl 1-hydroxy-6-oxo-2
      cyclohexenecarboxylate. The absolute configuration of (-)-idesolide is determined
      to be 2R,2'S,3aS,7aR.

PMID- 20136118
TI  - Fate of amoxicillin in mixed-culture bioreactors and its effects on microbial
      growth and resistance to silver ions.
AB  - This research focused on studying the fate of amoxicillin (AMX) in mixed-culture
      bioreactors and its effects on bacterial growth and bacterial resistance to
      silver-ion disinfection. The bioreactors were dosed with a range of AMX (10-70 mg
      L(-1) d(-1)) mimicking a biological treatment unit of a proposed water recovery
      system for long-term space missions. Aqueous-phase AMX concentrations in the
      bioreactors were monitored to characterize the kinetics of selected AMX fate
      processes. Specific growth rates and silver minimum effective concentrations
      (MECs) of the bacterial cultures were determined by assessing cell viability
      using flow cytometry. Hydrolysis, sorption, and biodegradation of AMX followed
      first-order kinetics with rate constants of 0.078, 0.083, and 0.13 d(-1),
      respectively. Specific growth rates of the AMX-dosed cultures were suppressed
      from 7% to 35% in order of increasing AMX dose as compared to the AMX-free
      control cultures. The AMX-treated cultures had higher silver MECs than the AMX
      free control cultures, indicating an enhanced bacterial resistance to silver ions
      as a result of the AMX exposure. Biosorption experiments revealed that the AMX
      treated cultures exhibited exclusion of silver ions from the cells as a potential
      mechanism for the enhanced resistance. This paper reports for the first time that
      low levels of AMX (<100 mg L(-1)) could induce bacterial cross-resistance to
      silver ion in an aqueous system mimicking an active biological system for
      wastewater treatment.

PMID- 20136119
TI  - Uranium-series constraints on radionuclide transport and groundwater flow at the
      Nopal I uranium deposit, Sierra Pena Blanca, Mexico.
AB  - Uranium-series data for groundwater samples from the Nopal I uranium ore deposit
      were obtained to place constraints on radionuclide transport and hydrologic
      processes for a nuclear waste repository located in fractured, unsaturated
      volcanic tuff. Decreasing uranium concentrations for wells drilled in 2003 are
      consistent with a simple physical mixing model that indicates that groundwater
      velocities are low ( approximately 10 m/y). Uranium isotopic constraints, well
      productivities, and radon systematics also suggest limited groundwater mixing and
      slow flow in the saturated zone. Uranium isotopic systematics for seepage water
      collected in the mine adit show a spatial dependence which is consistent with
      longer water-rock interaction times and higher uranium dissolution inputs at the
      front adit where the deposit is located. Uranium-series disequilibria
      measurements for mostly unsaturated zone samples indicate that (230)Th/(238)U
      activity ratios range from 0.005 to 0.48 and (226)Ra/(238)U activity ratios range
      from 0.006 to 113. (239)Pu/(238)U mass ratios for the saturated zone are <2 x 10(
      14), and Pu mobility in the saturated zone is >1000 times lower than the U
      mobility. Saturated zone mobility decreases in the order (238)U approximately
      (226)Ra > (230)Th approximately (239)Pu. Radium and thorium appear to have higher
      mobility in the unsaturated zone based on U-series data from fractures and
      seepage water near the deposit.

PMID- 20136120
TI  - Greenhouse gas emission footprints and energy use benchmarks for eight U.S.
      cities.
AB  - A hybrid life cycle-based trans-boundary greenhouse gas (GHG) emissions footprint
      is elucidated at the city-scale and evaluated for 8 US cities. The method
      incorporates end-uses of energy within city boundaries, plus cross-boundary
      demand for airline/freight transport and embodied energy of four key urban
      materials [food, water, energy (fuels), and shelter (cement)], essential for life
      in all cities. These cross-boundary activities contributed 47% on average more
      than the in-boundary GHG contributions traditionally reported for cities,
      indicating significant truncation at city boundaries of GHG emissions associated
      with urban activities. Incorporating cross-boundary contributions created
      convergence in per capita GHG emissions from the city-scale (average 23.7 mt
      CO(2)e/capita) to the national-scale (24.5 mt-CO(2)e/capita), suggesting that six
      key cross-boundary activities may suffice to yield a holistic GHG emission
      footprint for cities, with important policy ramifications. Average GHG
      contributions from various human activity sectors include buildings/facilities
      energy use (47.1%), regional surface transport (20.8%), food production (14.7%),
      transport fuel production (6.4%), airline transport (4.8%), long-distance freight
      trucking (2.8%), cement production (2.2%), and water/wastewater/waste processing
      (1.3%). Energy-, travel-, and key materials-consumption efficiency metrics are
      elucidated in these sectors; these consumption metrics are observed to be largely
      similar across the eight U.S. cities and consistent with national/regional
      averages.

PMID- 20136121
TI  - Structural basis for inverting the enantioselectivity of arylmalonate
      decarboxylase revealed by the structural analysis of the Gly74Cys/Cys188Ser
      mutant in the liganded form.
AB  - Arylmalonate decarboxylase catalyzes the enantioselective decarboxylation of
      alpha-aryl-alpha-methylmalonate to produce optically pure alpha-arylpropionate.
      The enzyme is comprised of two alpha/beta domains and contains an active site
      situated between the two domains. The site is formed by Tyr48, Gly74-Thr75-Ser76,
      Tyr126, and Cys188-Gly189-Gly190 residues. Since it has been observed that the
      Gly74Cys/Cys188Ser mutation inverts the enantioselectivity of the enzyme, we
      determined the crystal structure of the Gly74Cys/Cys188Ser mutant in the liganded
      form at a resolution of 1.45 A to understand the structural basis for this
      inversion. The overall structure of the enzyme overlapped well with that of the
      benzylphosphonate-associated wild-type enzyme, and the mutations had little
      effect on the structure of the active site. A ligand molecule bound to the active
      site in an unusual semiplanar conformation resembling the planar enediolate
      reaction intermediate could be assigned as phenyl acetate. The inversion in
      enantioselectivity by the paired mutation is explained by the mirror symmetry
      between Cys74 in the mutant and Cys188 of the wild type with respect to the
      carbon atom in the ligand to be protonated. Comparison of the wild-type and
      Gly74Cys mutant crystal structures suggested that ligand binding induces a
      positional shift of the Cys188-Gly189-Gly190 region toward the Gly74-Thr75 pair
      which provides two oxyanion holes necessary to stabilize the negatively charged
      enediolate reaction intermediate. The ligand binding also simultaneously induces
      the formation of a hydrophobic cluster over the active site cleft. Thus, AMDase
      is proposed to have "open" and "closed" conformations of the active site that are
      regulated by ligand binding. These results may provide an effective strategy for
      the rational design to invert the enantioselectivity of enzymes.

PMID- 20136122
TI  - Nano aptasensor for protective antigen toxin of anthrax.
AB  - We demonstrate a highly sensitive nano aptasensor for anthrax toxin through the
      detection of its polypeptide entity, protective antigen (PA toxin) using a PA
      toxin ssDNA aptamer functionalized single-walled carbon nanotubes (SWNTs) device.
      The aptamer was developed in-house by capillary electrophoresis systematic
      evolution of ligands by exponential enrichment (CE-SELEX) and had a dissociation
      constant (K(d)) of 112 nM. The aptasensor displayed a wide dynamic range spanning
      up to 800 nM with a detection limit of 1 nM. The sensitivity was 0.11 per nM, and
      it was reusable six times. The aptasensor was also highly selective for PA toxin
      with no interference from human and bovine serum albumin, demonstrating it as a
      potential tool for rapid and point-of-care diagnosis for anthrax.

PMID- 20136123
TI  - Mechanism of propene poisoning on Fe-ZSM-5 for selective catalytic reduction of
      NO(x) with ammonia.
AB  - Application of Fe-zeolites for urea-SCR of NO(x) in diesel engine is limited by
      catalyst deactivation with hydrocarbons. In this work, we investigated the effect
      of propene on the activity of Fe-ZSM-5 for selective catalytic reduction of NO(x)
      with ammonia (NH(3)-SCR), and proposed a deactivation mechanism of Fe(3+) active
      site blockage by propene residue. The NO conversion decreased in the presence of
      propene at various temperatures, while the effect was not significant when NO was
      replaced by NO(2) in the feed, especially at low temperatures (<300 degrees C).
      The surface area and pore volume were decreased due to carbonaceous deposition.
      The site blockage was mainly on Fe(3+) sites on which NO was to be oxidized to
      NO(2). The activity for NO oxidation to NO(2) was significantly inhibited on a
      propene poisoned catalyst below 400 degrees C. The adsorption of NH(3) on the
      Bronsted acid sites to form NH(4)(+) was not hindered even on the propene
      poisoned catalyst, and the amount of absorbed NH(3) was still abundant and enough
      to react with NO(2) to generate N(2). The hydrocarbon oxygenates such as formate,
      acetate, and containing nitrogen organic compounds were observed on catalyst
      surface, however, no graphitic carbonaceous deposit was formed.

PMID- 20136124
TI  - Measurement of benzenethiol adsorption to nanostructured Pt, Pd, and PtPd films
      using Raman spectroelectrochemistry.
AB  - Raman spectroscopy and electrochemical methods were used to study the behavior of
      the model adsorbate benzenethiol (BT) on nanostructured Pt, Pd, and PtPd
      electrodes as a function of applied potential. Benzenethiol adsorbs out of
      ethanolic solutions as the corresponding thiolate, and voltammetric stripping
      data reveal that BT is oxidatively removed from all of the nanostructured metals
      upon repeated oxidative and reductive cycling. Oxidative stripping potentials for
      BT increase in the order Pt < PtPd < Pd, indicating that BT adsorbs most strongly
      to nanoscale Pd. Yet, BT Raman scattering intensities, measured in situ over time
      scales of minutes to hours, are most persistent on the film of nanostructured Pt.
      Raman spectra indicate that adsorbed BT desorbs from nanoscale Pt at oxidizing
      potentials via cleavage of the Pt-S bond. In contrast, on nanoscale Pd and PtPd,
      BT is irreversibly lost due to cleavage of BT C-S bonds at oxidizing potentials,
      which leaves adsorbed sulfur oxides on Pd and PtPd films and effects the
      desulfurization of BT. While Pd and PtPd films are less sulfur-resistant than Pt
      films, palladium oxides, which form at higher potentials than Pt oxides,
      oxidatively desulfurize BT. In situ spectroelectrochemical Raman spectroscopy
      provides real-time, chemically specific information that complements the cyclic
      voltammetric data. The combination of these techniques affords a powerful and
      convenient method for guiding the development of sulfur-tolerant PEMFC catalysts.

PMID- 20136125
TI  - Photoelectrochemical processes in polymer-tethered CdSe nanocrystals.
AB  - We demonstrate the electrochemical capture of CdSe semiconductor nanocrystals
      (NCs), with thiophene-terminated carboxylic acid capping ligands, at the surfaces
      of electrodeposited poly(thiophene) films (i)
      poly((diethyl)propylenedixoythiophene), P(Et)(2)ProDOT; (ii)
      poly(propylenedioxythiophene), PProDOT; and (iii) poly(ethylenedioxythiophene),
      PEDOT, coupled with the exploration of their photoelectrochemical properties.
      Host polymer films were created using a kinetically controlled electrodeposition
      protocol on activated indium-tin oxide electrodes (ITO), producing conformal
      films that facilitate high rates of electron transfer. ProDOT-terminated, ligand
      capped CdSe-NCs were captured at the outer surface of the host polymer films
      using a unique pulse-potential step electrodeposition protocol, providing for
      nearly close-packed monolayers of the NCs at the host polymer/solution interface.
      These polymer-confined CdSe NCs were used as sensitizers in the
      photoelectrochemical reduction of methyl viologen (MV(+2)). High internal quantum
      efficiencies (IQEs) are estimated for photoelectrochemical sensitized MV(+2)
      reduction using CdSe NCs ranging from 3.1 to 7.0 nm diameters. Cathodic
      photocurrent at high MV(+2) concentrations are limited by the rate of hole
      capture by the host polymer from photoexcited NCs. The rate of this hole-capture
      process is determined by (a) the onset potential for reductive dedoping of the
      host polymer film; (b) the concentration ratio of neutral to oxidized forms of
      the host polymer ([P(n)]/[P(ox)]); and (c) the NC diameter, which controls its
      valence band energy, E(VB). These relationships are consistent with control of
      photoinduced electron transfer by Marcus-like excess free energy relationships.
      Our electrochemical assembly methods provide an enabling route to the capture of
      functional NCs in conducting polymer hosts in both photoelectrochemical and
      photovoltaic energy conversion systems.

PMID- 20136126
TI  - Phthalocyanine blends improve bulk heterojunction solar cells.
AB  - A core phthalocyanine platform allows engineering of the solubility properties
      the band gap, shifting the maximum absorption toward the red. A simple method for
      increasing the efficiency of heterojunction solar cells uses a self-organized
      blend of phthalocyanine chromophores fabricated by solution processing.

PMID- 20136127
TI  - Determination of beta-lactamase residues in milk using matrix-assisted laser
      desorption/ionization Fourier transform mass spectrometry.
AB  - A selective, fast, and effective enzyme assay based on matrix-assisted laser
      desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) for
      quantifying beta-lactamase, an illegal additive in milk products, has been
      reported. The strengths of the mass spectrometric assay are its response to all
      substrate and products, simple and direct detection of the conversion of
      substrate, and facile determination of enzyme activity. Also, MALDI MS is
      tolerant to many buffer salts and reagents without the requirement of complicated
      sample pretreatment procedures. In this study, the approach was used to detect
      the presence of beta-lactamases (BLA) in milk samples. The amount of BLA that
      could be determined in a milk sample is 6 x 10(-3) U x mL(-1) by this approach.
      To test the strategy, it has been applied to the fortified milk (adding a BLA
      product known as an antimicrobial destroyer). It is then tested whether the
      pasteurization procedure of the milk process affects the activity of BLA in milk
      samples. This study offers a perspective into the utility of MALDI-FTMS as an
      alternative detection tool for BLA screening in milk.

PMID- 20136128
TI  - Development of a candidate reference measurement procedure for the determination
      of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum using isotope
      dilution liquid chromatography-tandem mass spectrometry.
AB  - Vitamin D exists in two major forms, vitamin D(3) and vitamin D(2). Vitamin D
      helps the body absorb calcium and promote optimal bone health. Both forms of
      vitamin D are metabolized to 25-hydroxyvitamin D in the body, and the levels of
      25-hydroxyvitamin D(3) [25(OH)D(3)] and 25-hydroxyvitamin D(2) [25(OH)D(2)] in
      serum are considered the best indicators of vitamin D status. A candidate
      reference measurement procedure for serum 25(OH)D(3) and 25(OH)D(2) has been
      developed and critically evaluated. The deuterated compounds 25(OH)D(3)-d(3) and
      25(OH)D(2)-d(3) are used as internal standards for 25(OH)D(3) and 25(OH)D(2),
      respectively. The 25(OH)D(3) and 25(OH)D(2) and their respective labeled internal
      standards are simultaneously extracted from serum using liquid-liquid extraction
      prior to reversed-phase liquid chromatography-tandem mass spectrometry (LC
      MS/MS). Chromatographic separation was performed using a cyano (CN) column for
      both 25(OH)D(3) and 25(OH)D(2). Atmospheric pressure chemical ionization (APCI)
      in the positive ion mode and multiple reaction monitoring (MRM) were used for LC
      MS/MS. The accuracy of the method was evaluated by recovery studies of measuring
      25-hydroxyvitamin D [25(OH)D] in spiked samples with known 25(OH)D levels. The
      recoveries of the added 25(OH)D(3) and 25(OH)D(2) ranged from 99.0% to 101.0%.
      The absolute recoveries with this method were 97% and 92% for 25(OH)D(3) and
      25(OH)D(2), respectively. Excellent precision was obtained with between-set
      coefficients of variation (CVs) of 0.2-0.6% for 25(OH)D levels >1 ng/g and within
      2% for the level of <1 ng/g. Chromatographic separation of 25(OH)D(3) and
      25(OH)D(2) from their respective isomers 3-epi-25(OH)D(3) and 3-epi-25(OH)D(2)
      was achieved. The limit of detection at a signal-to-noise ratio of approximately
      3 was 40 pg of 25(OH)D on column (or approximately 0.15 ng/g as expressed as a
      concentration). This candidate reference measurement procedure for serum
      25(OH)D(3) and 25(OH)D(2) demonstrates good accuracy and precision and low
      susceptibility to interferences. It can be used to provide an accuracy base to
      which clinical methods for 25(OH)D(3) and 25(OH)D(2) can be compared and that
      will serve as a standard of higher order for measurement traceability.

PMID- 20136129
TI  - Development and application of a near-infrared fluorescence probe for oxidative
      stress based on differential reactivity of linked cyanine dyes.
AB  - Reactive oxygen species (ROS) operate as signaling molecules under various
      physiological conditions, and overproduction of ROS is involved in the
      pathogenesis of many diseases. Therefore, fluorescent probes for visualizing ROS
      are promising tools with which to uncover the molecular mechanisms of
      physiological and pathological processes and might also be useful for diagnosis.
      Here we describe a novel fluorescence probe, FOSCY-1, operating in the
      physiologically favorable near-infrared region. The probe consists of two
      differentially ROS-reactive cyanine dyes connected by a linker; reaction of the
      more susceptible dye with ROS releases intramolecular fluorescence quenching of
      the less susceptible dye. We successfully applied this probe to detect ROS
      produced by HL60 cells and porcine neutrophils and for imaging oxidative stress
      in a mouse model of peritonitis.

PMID- 20136130
TI  - Sol-gel immobilization of lactate oxidase from organic solvent: toward the
      advanced lactate biosensor.
AB  - We report on the novel protocol for enzyme immobilization into gel of siloxanes
      using water-organic mixtures with the high content of organic solvent as a
      reaction medium. Hydrolysis of alkoxysilanes carried out without excessive
      dilution with water resulted in more active and stable enzyme containing
      membranes. Immobilization of an inherently labile lactate oxidase according to
      the proposed sol-gel protocol over Prussian Blue modified electrode resulted in
      an advanced lactate biosensor characterized with a sensitivity of 0.18 A M(-1)
      cm(-2) in the flow injection analysis (FIA) mode over a wide dynamic range. A
      comparison with the known sensors has shown that analytical performances of the
      elaborated lactate biosensor are advantageous over both published systems and
      commercialized devices. The biosensor shows an appropriate stability and is
      suitable for clinical analysis (including noninvasive diagnostics) and food
      quality control.

PMID- 20136131
TI  - Kinetic and thermodynamic analysis of processes relevant to initiation of olefin
      metathesis by ruthenium phosphonium alkylidene catalysts.
AB  - Initiation processes in a family of ruthenium phosphonium alkylidene catalysts,
      some of which are commercially available, are presented. Seven 16-electron
      zwitterionic catalyst precursors of general formula
      (H(2)IMes)(Cl)(3)Ru=C(H)P(R(1))(2)R(2) (R(1) = R(2) = C(6)H(11), C(5)H(9), i
      C(3)H(7), 1-Cy(3)-Cl, 1-Cyp(3)-Cl, 1-(i)Pr(3)-Cl; R(1) = C(6)H(11), R(2) =
      CH(2)CH(3), 1-EtCy(2)-Cl; R(1) = C(6)H(11), R(2) = CH(3), 1-MeCy(2)-Cl; R(1) = i
      C(3)H(7), R(2) = CH(2)CH(3), 1-Et(i)Pr(2)-Cl; R(1) = i-C(3)H(7), R(2) = CH(3), 1
      Me(i)Pr(2)-Cl) were prepared. These compounds can be converted to the metathesis
      active 14-electron phosphonium alkylidenes by chloride abstraction with
      B(C(6)F(5))(3). The examples with symmetrically substituted phosphonium groups
      exist as monomers in solution and are rapid initiators of olefin metathesis
      reactions. The unsymmetrically substituted phosphonium alkylidenes are observed
      to undergo reversible dimerization, the extent of which is dependent on the
      steric bulk of the phosphonium group. Kinetic and thermodynamic parameters of
      these equilibria are presented, as well as experiments that show that metathesis
      is only initiated through the monomers; thus dedimerization is required for
      initiation. In another detailed study, the series of catalysts 1-R(3) were
      reacted with o-isopropoxystyrene under pseudo-first-order conditions to quantify
      second-order olefin binding rates. A more complex initiation process was observed
      in that the rates were accelerated by catalytic amounts of ethylene produced in
      the reaction with o-isopropoxystyrene. The ability of the catalyst to generate
      ethylene is related to the nature of the phosphonium group, and initiation rates
      can be dramatically increased by the intentional addition of a catalytic amount
      of ethylene.

PMID- 20136132
TI  - 2D IR line shapes probe ovispirin peptide conformation and depth in lipid
      bilayers.
AB  - We report a structural study on the membrane binding of ovispirin using 2D IR
      line shape analysis, isotope labeling, and molecular dynamics simulations.
      Ovispirin is an antibiotic polypeptide that binds to the surfaces of membranes as
      an alpha-helix. By resolving individual backbone vibrational modes (amide I)
      using 1-(13)C=(18)O labeling, we measured the 2D IR line shapes for 15 of the 18
      residues in this peptide. A comparison of the line shapes reveals an oscillation
      in the inhomogeneous line width that has a period equal to that of an alpha-helix
      (3.6 amino acids). The periodic trend is caused by the asymmetric environment of
      the membrane bilayer that exposes one face of the alpha-helix to much stronger
      environmental electrostatic forces than the other. We compare our experimental
      results to 2D IR line shapes calculated using the lowest free energy structure
      identified from molecular dynamics simulations. These simulations predict a
      periodic trend similar to the experiment and lead us to conclude that ovispirin
      lies in the membrane just below the headgroups, is tilted, and may be kinked.
      Besides providing insight into the antibiotic mechanism of ovispirin, our
      procedure provides an infrared method for studying peptide and protein structures
      that relies on the natural vibrational modes of the backbone. It is a
      complementary method to other techniques that utilize line shapes, such as
      fluorescence, NMR, and ESR spectroscopies, because it does not require mutations,
      the spectra can be quantitatively simulated using molecular dynamics, and the
      technique can be applied to difficult-to-study systems like ion channels,
      aggregated proteins, and kinetically evolving systems.

PMID- 20136133
TI  - New modes for the osmium-catalyzed oxidative cyclization.
AB  - The osmium-catalyzed oxidative cyclization of amino alcohol initiators formally
      derived from 1,4-dienes is an effective method for the construction of
      pyrrolidines, utilizing a novel reoxidant (4-nitropyridine N-oxide = NPNO). The
      cyclization of enantiopure syn- and anti-amino alcohols gives rise to enantiopure
      cis- and trans-2,5-disubstituted pyrrolidines, respectively. Moreover, the
      cyclization of bis-homoallylic amines bearing an exocyclic chelating group is
      shown to be a complementary method for trans-pyrrolidine formation.

PMID- 20136134
TI  - Recommendations for fluorescence instrument qualification: the new ASTM Standard
      Guide.
AB  - Aimed at improving quality assurance and quantitation for modern fluorescence
      techniques, ASTM International (ASTM) is about to release a Standard Guide for
      Fluorescence, reviewed here. The guide's main focus is on steady state
      fluorometry, for which available standards and instrument characterization
      procedures are discussed along with their purpose, suitability, and general
      instructions for use. These include the most relevant instrument properties
      needing qualification, such as linearity and spectral responsivity of the
      detection system, spectral irradiance reaching the sample, wavelength accuracy,
      sensitivity or limit of detection for an analyte, and day-to-day performance
      verification. With proper consideration of method-inherent requirements and
      limitations, many of these procedures and standards can be adapted to other
      fluorescence techniques. In addition, procedures for the determination of other
      relevant fluorometric quantities including fluorescence quantum yields and
      fluorescence lifetimes are briefly introduced. The guide is a clear and concise
      reference geared for users of fluorescence instrumentation at all levels of
      experience and is intended to aid in the ongoing standardization of fluorescence
      measurements.

PMID- 20136135
TI  - Pillared MFI zeolite nanosheets of a single-unit-cell thickness.
AB  - Zeolite MFI nanosheets of 2-nm thickness have been hydrothermally synthesized via
      cooperative assembly between silica and an organic surfactant, which is
      functionalized with a diquaternary ammonium group. The zeolite nanosheets have
      been further assembled into their ordered multilamellar mesostructure through
      hydrophobic interactions between the surfactant tails located outside the zeolite
      nanosheet. This assembly process involves successive transformations from an
      initially hexagonal mesophase to a multilamellar mesophase without crystallinity
      and then to a lamellar mesophase with a crystalline zeolite framework. The
      mesopore volume in the interlamellar space could be retained by supporting the
      zeolite nanosheets with silica pillars, as in pillared clays, even after
      surfactant removal by calcination. The mesopore diameters could be controlled
      according to the surfactant tail lengths. Due to the interlamellar structural
      coherence, the hierarchically mesoporous/microporous zeolite could exhibit small
      angle X-ray diffraction peaks up to the fourth-order reflections corresponding to
      the interlayer distance. In addition, an Ar adsorption analysis and transmission
      electron microscopic investigation indicated that the pillars were highly likely
      to be built with an MFI structure. The present approach using a zeolite structure
      directing functional group contained in a surfactant would be suitable for the
      synthesis of other related nanomorphous zeolites in the future.

PMID- 20136136
TI  - Surface plasmon coupled circular dichroism of Au nanoparticles on peptide
      nanotubes.
AB  - Au nanoparticles grown on D- and L-isomers of diphenylalanine peptide nanotubes
      showed a bisignated CD signal at their surface plasmon frequency with positive
      and negative couplets, respectively. The surface plasmon coupled CD signal in
      these hybrid systems originates from the asymmetric organization of Au
      nanoparticles on peptide nanotubes. Mirror image relationship in the CD spectra
      clearly indicates that the chiral molecules on the nanotubes drive the
      organization of nanoparticles in two different ways.

PMID- 20136137
TI  - Resonating valence bond and sigma-charge density wave phases in a benzannulated
      phenalenyl radical.
AB  - We report the preparation of the first benzannulated phenalenyl neutral radical
      conductor (18), and we show that the compound displays unprecedented solid state
      behavior: the structure is dominated by two sets of intermolecular interactions:
      (1) a pi-chain structure with superimposed pi-overlap of the benzannulated
      phenalenyls along [0 0 1], and (2) an interchain overlap involving a pair of
      carbon atoms (C4) along [0 1 0]. The pi-chain-type stacking motif is reminiscent
      of previously reported phenalenyl radicals and the room temperature structure
      (space group P2/c) together with the conductivity of sigma(RT) = 0.03 S/cm and
      the Pauli-like magnetic susceptibility are best described by the resonating
      valence bond (RVB) model. The interchain interaction is unstable with respect to
      the formation of a sigma-charge density wave (sigma-CDW) involving pairs of C4
      carbon atoms between adjacent radicals and this phase is characterized by the
      P2(1)/c space group which involves a doubling of the unit cell along the [0 1 0]
      direction. The RVB and CDW phases compete for structural occupancy throughout the
      whole temperature range (15-293 K) with the RVB phase predominating at 15 and 293
      K and the sigma-CDW phase achieving a maximum structural occupancy of about 60%
      at 150 K where it produces clearly discernible effects on the magnetism and
      conductivity.

PMID- 20136138
TI  - Synthesis of Pd-Au bimetallic nanocrystals via controlled overgrowth.
AB  - This paper describes the synthesis of Pd-Au bimetallic nanocrystals with
      controlled morphologies via a one-step seeded-growth method. Two different
      reducing agents, namely, L-ascorbic acid and citric acid, were utilized for the
      reduction of HAuCl(4) in an aqueous solution to control the overgrowth of Au on
      cubic Pd seeds. When L-ascorbic acid was used as the reducing agent, conformal
      overgrowth of Au on the Pd nanocubes led to the formation of Pd-Au nanocrystals
      with a core-shell structure. On the contrary, localized overgrowth of Au was
      observed when citric acid was used as the reducing agent, producing Pd-Au
      bimetallic dimers. Through this morphological control, we were able to tune the
      localized surface plasmon resonance peaks of Pd-Au bimetallic nanostructures in
      the visible region.

PMID- 20136139
TI  - Editing mechanism of aminoacyl-tRNA synthetases operates by a hybrid
      ribozyme/protein catalyst.
AB  - Aminoacyl-tRNA synthetases (aaRSs) are critical for the translational process,
      catalyzing the attachment of specific amino acids to their cognate tRNAs. To
      ensure formation of the correct aminoacyl-tRNA, and thereby enhance the
      reliability of translation, several aaRSs have an editing capability that hinders
      formation of misaminoacylated tRNAs. We investigated theoretically the mechanism
      of the editing reaction for a class I enzyme, leucyl-tRNA synthetase (LeuRS),
      complexed with a misaminoacylated tRNA(Leu), employing ab initio hybrid quantum
      mechanical/molecular mechanical potentials in conjunction with molecular dynamics
      simulations. It is shown that the water molecule that acts as the nucleophile in
      the editing reaction is activated by a 3'-hydroxyl group at the 3'-end of
      tRNA(Leu) and that the O2' atom of the leaving group of the substrate is capped
      by one of the water's hydrogen atoms. Thus, it is shown that editing is a self
      cleavage reaction of the tRNA and so it is the tRNA, and not the protein, that
      drives the reaction. The protein does, however, have an important stabilizing
      effect on some high-energy intermediates along the reaction path, which is more
      efficient than the ribozyme would be alone. This indicates that editing is
      achieved by a novel "hybrid ribozyme/protein catalyst". Analysis of existing
      experimental data and additional modeling shows that this ribozymal mechanism
      appears to be widespread, occurring in the ribosome as well as in other aaRSs. It
      also suggests transitional forms that could have played an important role in the
      RNA world hypothesis for the origin of life.

PMID- 20136140
TI  - Chemical solution deposition of epitaxial carbide films.
AB  - Carbide films exhibit many unique properties. The development of a versatile and
      simple technique for the deposition of carbide films will enable a wide range of
      technological applications. Here we report a cost-effective chemical solution
      deposition or polymer-assisted deposition method for growing epitaxial carbide
      (including TiC, VC, and TaC) films. These epitaxial carbide films exhibit
      structural and physical properties similar to the films grown by vapor deposition
      methods.

PMID- 20136141
TI  - A series of peroxomanganese(III) complexes supported by tetradentate aminopyridyl
      ligands: detailed spectroscopic and computational studies.
AB  - A set of four [Mn(II)(L(7)py(2)(R))](2+) complexes, supported by the tetradentate
      1,4-bis(2-pyridylmethyl)-1,4-diazepane ligand and derivatives with pyridine
      substituents in the 5 (R = Br) and 6 positions (R = Me and MeO), are reported. X
      ray crystal structures of these complexes all show the L(7)py(2)(R) ligands bound
      to give a trans complex. Treatment of these Mn(II) precursors with either
      H(2)O(2)/Et(3)N or KO(2) in MeCN at -40 degrees C results in the formation of
      peroxomanganese complexes [Mn(III)(O(2))(L(7)py(2)(R))](+) differing only in the
      identity of the pyridine ring substituent. The electronic structures of two of
      these complexes, [Mn(III)(O(2))(L(7)py(2)(H))](+) and
      [Mn(III)(O(2))(L(7)py(2)(Me))](+), were examined in detail using electronic
      absorption, low-temperature magnetic circular dichroism (MCD) and variable
      temperature variable-field (VTVH) MCD spectroscopies to determine ground-state
      zero-field splitting (ZFS) parameters and electronic transition energies,
      intensities, and polarizations. DFT and TD-DFT computations were used to validate
      the structures of [Mn(III)(O(2))(L(7)py(2)(H))](+) and
      [Mn(III)(O(2))(L(7)py(2)(Me))](+), further corroborating their assignment as
      peroxomanganese(III) species. While these complexes exhibit similar ZFS
      parameters, their low-temperature MCD spectra reveal significant shifts in
      electronic transition energies that are correlated to differences in Mn-O(2)
      interactions among these complexes. Taken together, these results indicate that,
      while the [Mn(III)(O(2))(L(7)py(2)(H))](+) complex exhibits symmetric Mn
      O(peroxo) bond lengths, consistent with a side-on bound peroxo ligand, the peroxo
      ligand of the [Mn(III)(O(2))(L(7)py(2)(Me))](+) complex is bound in a more end-on
      fashion, with asymmetric Mn-O(peroxo) distances. This difference in binding mode
      is rationalized in terms of the greater electron-donating abilities of the methyl
      appended pyridines and suggests a simple way to modulate Mn(III)-O(2) bonding
      through ligand perturbations.

PMID- 20136142
TI  - Regio- and stereoselective Ni-catalyzed 1,4-hydroboration of 1,3-dienes: access
      to stereodefined (Z)-allylboron reagents and derived allylic alcohols.
AB  - A catalytic regio- and stereoselective 1,4-hydroboration of 1,3-dienes was
      accomplished with pinacolborane in the presence of Ni(cod)(2) and PCy(3). This
      reaction exhibits broad substrate scope operating on a range of substituted
      dienes and occurs with generally high levels of selectivity and efficiency.
      Reactivity patterns suggest that the reactive conformation of the diene is the S
      cis form. The intermediate allylboronate can be oxidized to stereodefined allylic
      alcohols or can be used in stereoselective carbonyl addition reactions.

PMID- 20136143
TI  - Total synthesis of chloptosin, a potent apoptosis-inducing cyclopeptide.
AB  - A bidirectional total synthesis of chloptosin has been achieved in 16 operations
      (32 individual reactions) and 3% overall yield from the readily available
      materials. Palladium-catalyzed tryptophan synthesis, diastereoselective
      selenocyclization and oxidative deselenation successfully served as key steps in
      construction of the dimeric core amino acid. 2-Bromo-1-ethyl pyridinium
      tetrafluoroborate was efficiently employed in the peptide couplings with spatial
      encumbrance in this synthesis.

PMID- 20136144
TI  - Hysteresis of colloid retention and release in saturated porous media during
      transients in solution chemistry.
AB  - Saturated packed column and micromodel transport studies were conducted to gain
      insight on mechanisms of colloid retention and release under unfavorable
      attachment conditions. The initial deposition of colloids in porous media was
      found to be a strongly coupled process that depended on solution chemistry and
      pore space geometry. During steady state chemical conditions, colloid deposition
      was not a readily reversible process, and micromodel photos indicated that
      colloids were immobilized in the presence of fluid drag. Upon stepwise reduction
      in eluting solution ionic strength (IS), a sharp release of colloids occurred in
      each step which indicates that colloid retention depends on a balance of applied
      (hydrodynamic) and resisting (adhesive) torques which varied with pore space
      geometry, surface roughness, and interaction energy. When the eluting fluid IS
      was reduced to deionized water, the final retention locations occurred near grain
      grain contacts, and colloid aggregation was sometimes observed in micromodel
      experiments. Significant amounts of colloid retention hysteresis with IS were
      observed in the column experiments, and it depended on the porous medium (glass
      beads compared with sand), the colloid size (1.1 and 0.5 mum), and on the initial
      deposition IS. These observations were attributed to weak adhesive interactions
      that depended on the double layer thickness (e.g., the depth of the secondary
      minimum and/or nanoscale heterogeneity), colloid mass transfer on the solid phase
      to regions where the torque and force balances were favorable for retention, the
      number and extent of grain-grain contacts, and surface roughness.

PMID- 20136145
TI  - Modulating the pH-activity profile of cellulase by substitution: replacing the
      general base catalyst aspartate with cysteinesulfinate in cellulase A from
      Cellulomonas fimi.
AB  - Cellulase A (CenA) from Cellulomonas fimi is an inverting glycoside hydrolase and
      a member of family 6 of the CAZy database classification system. We replaced its
      putative catalytic base aspartyl residues, Aps392 and Asp216, with
      cysteinesulfinate using a combination of site-directed mutagenesis and chemical
      modification to investigate the applicability of this approach for the modulation
      of enzymatic properties. The substituted cysteinyl residues were oxidized to
      cysteinesulfinic acid with hydrogen peroxide, and the resulting protein products
      were demonstrated to retain their native structure. Oxidation of the Asp392Cys
      mutant enzyme restored 52% of wild-type activity when assessed at pH 7.5, whereas
      Asp216Cys CenA remained inactive. This suggests that Asp216 is not the catalytic
      base and provides further support for Asp392 performing this role. Similar
      substitution of the catalytic acid residue Asp252 or the catalytic nucleophile of
      the retaining enzyme Cel5A from Thermobifida fusca failed to produce active
      enzymes. This indicates a potential utility of this approach for uniquely
      identifying catalytic base residues. The replacement of Asp392 with
      cysteinesulfinate induced an acidic shift in the pH profile of the enzyme such
      that this enzyme derivative was more active than wild-type CenA below pH 5.5.
      These data demonstrate the potential of combining site-directed mutagenesis with
      chemical modification as a viable approach for the modulation of cellulases, and
      potentially other glycoside hydrolases, at low pH.

PMID- 20136146
TI  - Activation of Escherichia coli UDP-3-O-[(R)-3-hydroxymyristoyl]-N
      acetylglucosamine deacetylase by Fe2+ yields a more efficient enzyme with altered
      ligand affinity.
AB  - The metal-dependent deacetylase UDP-3-O-[(R)-3-hydroxymyristoyl]-N
      acetylglucosamine deacetylase (LpxC) catalyzes the first committed step in lipid
      A biosynthesis, the hydrolysis of UDP-3-O-myristoyl-N-acetylglucosamine to form
      UDP-3-O-myristoylglucosamine and acetate. Consequently, LpxC is a target for the
      development of antibiotics, nearly all of which coordinate the active site metal
      ion. Here we examine the ability of Fe(2+) to serve as a cofactor for wild-type
      Escherichia coli LpxC and a mutant enzyme (EcC63A), in which one of the ligands
      for the inhibitory metal binding site has been removed. LpxC exhibits higher
      activity (6-8-fold) with a single bound Fe(2+) as the cofactor compared to Zn(2+)
      LpxC; both metalloenzymes have a bell-shaped dependence on pH with similar pK(a)
      values, indicating that at least two ionizations are important for maximal
      activity. X-ray absorption spectroscopy experiments suggest that the catalytic
      metal ion bound to Fe(2+)-EcLpxC is five-coordinate, suggesting that catalytic
      activity may correlate with coordination number. Furthermore, the ligand affinity
      of Fe(2+)-LpxC compared to the Zn(2+) enzyme is altered by up to 6-fold. In
      contrast to Zn(2+)-LpxC, the activity of Fe(2+)-LpxC is redox-sensitive, and a
      time-dependent decrease in activity is observed under aerobic conditions. The
      LpxC activity of crude E. coli cell lysates is also aerobically sensitive,
      consistent with the presence of Fe(2+)-LpxC. These data indicate that EcLpxC can
      use either Fe(2+) or Zn(2+) to activate catalysis in vitro and possibly in vivo,
      which may allow LpxC to function in E. coli grown under different environmental
      conditions.

PMID- 20136147
TI  - Amplitude of pancreatic lipase lid opening in solution and identification of spin
      label conformational subensembles by combining continuous wave and pulsed EPR
      spectroscopy and molecular dynamics.
AB  - The opening of the lid that controls the access to the active site of human
      pancreatic lipase (HPL) was measured from the magnetic interaction between two
      spin labels grafted on this enzyme. One spin label was introduced at a rigid
      position in HPL where an accessible cysteine residue (C181) naturally occurs. A
      second spin label was covalently bound to the mobile lid after introducing a
      cysteine residue at position 249 by site-directed mutagenesis. Double electron
      electron resonance (DEER) experiments allowed the estimation of a distance of 19
      +/- 2 A between the spin labels when bilabeled HPL was alone in a frozen
      solution, i.e., with the lid in the closed conformation. A magnetic interaction
      was however detected by continuous wave EPR experiments, suggesting that a
      fraction of bilabeled HPL contained spin labels separated by a shorter distance.
      These results could be interpreted by the presence of two conformational
      subensembles for the spin label lateral chain at position 249 when the lid was
      closed. The existence of these conformational subensembles was revealed by
      molecular dynamics experiments and confirmed by the simulation of the EPR
      spectrum. When the lid opening was induced by the addition of bile salts and
      colipase, a larger distance of 43 +/- 2 A between the two spin labels was
      estimated from DEER experiments. The distances measured between the spin labels
      grafted at positions 181 and 249 were in good agreement with those estimated from
      the known X-ray structures of HPL in the closed and open conformations, but for
      the first time, the amplitude of the lid opening was measured in solution or in a
      frozen solution in the presence of amphiphiles.

PMID- 20136148
TI  - p90 Ribosomal S6 kinase 2, a novel GPCR kinase, is required for growth factor
      mediated attenuation of GPCR signaling.
AB  - The 5-hydroxytryptamine 2A (5-HT(2A)) receptor is a member of the G protein
      coupled receptor superfamily (GPCR) and plays a key role in transducing a variety
      of cellular signals elicited by serotonin (5-HT; 5-hydroxytryptamine) in both
      peripheral and central tissues. Recently, we discovered that the ERK/MAPK
      effector p90 ribosomal S6 kinase 2 (RSK2) phosphorylates the 5-HT(2A) receptor
      and attenuates 5-HT(2A) receptor signaling. This raised the intriguing
      possibility of a regulatory paradigm whereby receptor tyrosine kinases (RTKs)
      attenuate GPCR signaling (i.e., "inhibitory cross-talk") by activating RSK2
      [Strachan et al. (2009) J. Biol. Chem. 284, 5557-5573]. We report here that
      activation of multiple endogenous RTKs such as the epidermal growth factor
      receptor (EGFR), the platelet-derived growth factor receptor (PDGFR), and ErbB4
      significantly attenuates 5-HT(2A) receptor signaling in a variety of cell types
      including mouse embryonic fibroblasts (MEFs), mouse vascular smooth muscle cells
      (mVSMCs), and primary cortical neurons. Importantly, genetic deletion of RSK2
      completely prevented signal attenuation, thereby suggesting that RSK2 is a
      critical mediator of inhibitory cross-talk between RTKs and 5-HT(2A) receptors.
      We also discovered that P2Y purinergic receptor signaling was similarly
      attenuated following EGFR activation. By directly testing multiple endogenous
      growth factors/RTK pathways and multiple Gq-coupled GPCRs, we have now
      established a cellular mechanism whereby RTK signaling cascades act via RSK2 to
      attenuate GPCR signaling. Given the pervasiveness of growth factor signaling,
      this novel regulatory mechanism has the potential to explain how 5-HT(2A)
      receptors are regulated in vivo, with potential implications for human diseases
      in which 5-HT(2A) or RTK activity is altered (e.g., neuropsychiatric and
      neurodevelopmental disorders).

PMID- 20136149
TI  - Reconstruction and analysis of human liver-specific metabolic network based on
      CNHLPP data.
AB  - Liver is the largest internal organ in the body that takes central roles in
      metabolic homeostasis, detoxification of various substances, as well as in the
      synthesis and storage of nutrients. To fulfill these complex tasks, thousands of
      biochemical reactions are going on in liver to cope with a wide range of foods
      and environmental variations, which are densely interconnected into an intricate
      metabolic network. Here, the first human liver-specific metabolic network was
      reconstructed according to proteomics data from Chinese Human Liver Proteome
      Project (CNHLPP), and then investigated in the context of the genome-scale
      metabolic network of Homo sapiens. Topological analysis shows that this organ
      specific metabolic network exhibits similar features as organism-specific
      networks, such as power-law degree distribution, small-world property, and bow
      tie structure. Furthermore, the structure of liver network exhibits a modular
      organization where the modules are formed around precursors from primary
      metabolism or hub metabolites from derivative metabolism, respectively. Most of
      the modules are dominated by one major category of metabolisms, while enzymes
      within same modules have a tendency of being expressed concertedly at protein
      level. Network decomposition and comparison suggest that the liver network
      overlays a predominant area in the global metabolic network of H. sapiens genome;
      meanwhile the human network may develop extra modules to gain more specialized
      functionality out of liver. The results of this study would permit a high-level
      interpretation of the metabolite information flow in human liver and provide a
      basis for modeling the physiological and pathological metabolic states of liver.

PMID- 20136150
TI  - Altering the energy landscape of virus self-assembly to generate kinetically
      trapped nanoparticles.
AB  - Controlling self-assembly is critical to the advancement of nanotechnology. A
      rugged or crenated assembly energy surface can redirect assembly off path. By
      using a defined starting point and an energy surface made rough by a strong
      association energy, we can impose entirely new assembly paths and products.
      Normally, the coat protein (CP) of the Cowpea Chlorotic Mottle Virus (CCMV)
      assembles into virus-like 28 nm diameter icosahedral particles. Here we have
      started with the coat protein trapped in a rod-like structure in complex with
      DNA. When these 17 nm diameter rods are placed under the same condition, low pH,
      that normally leads to assembly of 28 nm diameter particles, we instead obtain 17
      nm capsids. The extrusion of all-pentamer capsids from the hexagonal lattice of
      the rod demonstrates the importance of the starting state for controlled
      assembly.

PMID- 20136151
TI  - Organometallic trinuclear niobium cluster complex in aqueous solution: synthesis
      and characterization of niobium complexes containing Nb(3)(mu-eta(2):eta(2)(
      perpendicular)-NCCH(3))(mu(2)-O)(3)(6+) cluster core.
AB  - The synthesis and characterization of an organometallic trinuclear oxo-bridged
      niobium cluster complex with perpendicularly coordinated mu(3)-eta(2):eta(2)(
      perpendicular)-acetonitrile ligand in aqueous solution is reported. Reaction of
      NbCl(5) in acetonitrile with aluminum under argon followed by reaction with
      aqueous hydrochloric acid affords, after suitable workup, the isolation of the
      organometallic [Nb(3)(mu-eta(2):eta(2)-NCCH(3))O(3)(H(2)O)(9)](6+) aqua ion by
      cation-exchange chromatography. The purple niobium aqua ion in 2 M HCl shows a
      small peak at 365 nm (epsilon approximately 511 M(-1) cm(-1) per Nb) and a broad
      peak at 565 nm (epsilon approximately 335 M(-1) cm(-1)) in the UV-visible region.
      It is electron paramagnetic resonance (EPR)-active (g = 1.98), but no hyperfine
      interaction with the (93)Nb nuclear spin (I = 9/2) was observed. The cyclic
      voltammogram of [Nb(3)(mu-eta(2):eta(2)-NCCH(3))O(3)(H(2)O)(9)](6+) in 4 M HCl on
      edge-plane pyrolytic graphite electrode at 50 mV s(-1) in the potential range 
      1.2 V to +1.1 V (vs SCE) exhibits three anodic peaks at -0.12, +0.53, and +0.85 V
      and a large cathodic peak at -0.91 V with a slight shoulder at about -0.8 V. The
      purple aqua ion reacted with potassium thiocyanate to give the green thiocyanate
      derivative, which was crystallized as ((CH(3))(3)NH)(3)[Nb(3)(mu-eta(2):eta(2)
      NCCH(3))O(3)(NCS)(9)].2.5H(2)O (1) and subjected to X-ray structure analysis.
      Density-functional theory (DFT) calculations fully supported the structure of the
      cluster.

PMID- 20136152
TI  - Heterometallic Ln/Hg tellurido clusters.
AB  - "Ln(TePh)(3)" (Ln = Er, Tm, Lu), prepared in situ by the reduction of PhTeTePh
      with elemental Ln in the presence of Hg catalyst, reacts with elemental Te to
      give heterometallic clusters with the formula (py)(7)Ln(3)HgTe(4)(TePh)(3).
      Structural characterization of all three isostructural derivatives reveals a
      cubane arrangement of metal ions, with a distorted tetrahedral Hg(II) ion
      coordinated to three mu(3) coordinate Te(2-) and a terminal TePh ligand. There
      are two chemically inequivalent types of octahedral Ln(III) ions, one bound to
      three Te(2-) and three pyridine donors, and two that coordinate two pyridine,
      three Te(2-), and a terminal TePh ligand. The Lu compound decomposes at elevated
      temperatures to give LuTe.

PMID- 20136153
TI  - Iridium-catalyzed (Z)-trialkylsilylation of terminal olefins.
AB  - A complex of commercial [Ir(OMe)(cod)](2) and 4,4-di-tert-butyl-2,2-bipyridine
      (dtbpy) catalyzes the Z-selective, dehydrative silylation of terminal alkenes,
      but not 1,2-disubstituted alkenes, with triethylsilane or benzyldimethylsilane in
      THF at 40 degrees C. Yields and Z-stereoselectivity were significantly improved
      by 2-norbornene, in contrast with other sacrificial alkenes. The reaction is
      compatible with many functional groups including epoxides, ketones, amides,
      alcohols, esters, halides, ketals, and silanes. alpha,beta-Unsaturated esters
      were unreactive. The reaction probably proceeds through a Heck-type mechanism.

PMID- 20136154
TI  - Regioselective control in the oxidative cleavage of 4,6-O-benzylidene acetals of
      glycopyranosides by dimethyldioxirane.
AB  - The oxidative cleavage of 4,6-O-benzylidene acetals of glycopyranosides using
      dimethyldioxirane (DMDO) leads to the corresponding hydroxy-benzoates in
      excellent yields. With a proper choice of the neighboring protecting groups, this
      oxidative fragmentation provides the 6- or 4-hydroxyl derivatives in a highly
      regioselective manner.

PMID- 20136155
TI  - Synthesis of a triptycene-derived bisparaphenylene-34-crown-10 and its
      complexation with both paraquat and cyclobis(paraquat-p-phenylene).
AB  - A novel triptycene-derived bisparaphenylene-34-crown-10 (1) has been synthesized,
      and shown to form 1:1 stable complexes with both the paraquat G1.2PF(6) and the
      cyclobis(paraquat-p-phenylene) G2.4PF(6) in different complexation modes in
      solution and solid state. Moreover, it was found that both the complexes
      1.G1.2PF(6) and 1.G2.4PF(6) were formed by charge transfer interactions, and did
      not dissociate upon the first one-electron reduction process of the bipyridinium
      ring.

PMID- 20136156
TI  - Facile syntheses of enantiopure 3-hydroxypiperidine derivatives and 3
      hydroxypipecolic acids.
AB  - Facile syntheses of enantiopure trans- and cis-3-hydroxypiperidine derivatives
      and 3-hydroxypipecolic acids are reported, featuring Rh-catalyzed
      cyclohydrocarbonylation through common intermediates. A diaxial conformation in a
      2,3-disubstituted N-Boc-piperidinyl structure is revealed by an X-ray
      crystallographic analysis.

PMID- 20136157
TI  - Synthesis and biophysical evaluation of 2',4'-constrained 2'O-methoxyethyl and
      2',4'-constrained 2'O-ethyl nucleic acid analogues.
AB  - We have recently shown that combining the structural elements of 2'O-methoxyethyl
      (MOE) and locked nucleic acid (LNA) nucleosides yielded a series of nucleoside
      modifications (cMOE, 2',4'-constrained MOE; cEt, 2',4'-constrained ethyl) that
      display improved potency over MOE and an improved therapeutic index relative to
      that of LNA antisense oligonucleotides. In this report we present details
      regarding the synthesis of the cMOE and cEt nucleoside phosphoramidites and the
      biophysical evaluation of oligonucleotides containing these nucleoside
      modifications. The synthesis of the cMOE and cEt nucleoside phosphoramidites was
      efficiently accomplished starting from inexpensive commercially available
      diacetone allofuranose. The synthesis features the use of a seldom used 2
      naphthylmethyl protecting group that provides crystalline intermediates during
      the synthesis and can be cleanly deprotected under mild conditions. The synthesis
      was greatly facilitated by the crystallinity of a key mono-TBDPS-protected diol
      intermediate. In the case of the cEt nucleosides, the introduction of the methyl
      group in either configuration was accomplished in a stereoselective manner. Ring
      closure of the 2'-hydroxyl group onto a secondary mesylate leaving group with
      clean inversion of stereochemistry was achieved under surprisingly mild
      conditions. For the S-cEt modification, the synthesis of all four (thymine, 5
      methylcytosine, adenine, and guanine) nucleobase-modified phosphoramidites was
      accomplished on a multigram scale. Biophysical evaluation of the cMOE- and cEt
      containing oligonucleotides revealed that they possess hybridization and mismatch
      discrimination attributes similar to those of LNA but greatly improved resistance
      to exonuclease digestion.

PMID- 20136158
TI  - Aqueous iodine(III)-mediated stereoselective oxidative cyclization for the
      synthesis of functionalized fused dihydrofuran derivatives.
AB  - An efficient aqueous oxidative cyclization mediated by the combination of
      iodosobenzene with tetra-(n-butyl)ammonium iodide provides a new convenient and
      useful route to functionalized fused dihydrofuran derivatives in moderate to
      excellent yields with high diastereoselectivities.

PMID- 20136159
TI  - Palladium-catalyzed decarboxylative cross-coupling reaction between
      heteroaromatic carboxylic acids and aryl halides.
AB  - A full overview of the decarboxylative cross-coupling reaction between
      heteroaromatic carboxylic acids and aryl halides is described. This
      transformation employs palladium catalysts with short reaction times providing
      facile synthesis of aryl-substituted heteroaromatics. The effect of each reaction
      parameter including solvent, base, and additive employed as well as the full
      substrate scope of this transformation are reported. Mechanistic evidence is also
      disclosed that sheds light on possible reaction pathways.

PMID- 20136160
TI  - Modeling the reactions catalyzed by coenzyme B12-dependent enzymes.
AB  - Enzymes accelerate chemical reactions with an exceptional selectivity that makes
      life itself possible. Understanding the factors responsible for this efficient
      catalysis is of utmost importance in our quest to harness the tremendous power of
      enzymes. Computational chemistry has emerged as an important adjunct to
      experimental chemistry and biochemistry in this regard, because it provides
      detailed insights into the relationship between structure and function in a
      systematic and straightforward manner. In this Account, we highlight our recent
      high-level theoretical investigations toward this end in studying the radical
      based reactions catalyzed by enzymes dependent on coenzyme B(12) (or
      adenosylcobalamin, AdoCbl). In addition to their fundamental position in biology,
      the AdoCbl-dependent enzymes represent a valuable framework within which to
      understand Nature's method of efficiently handling high-energy species to execute
      very specific reactions. The AdoCbl-mediated reactions are characterized by the
      interchange of a hydrogen atom and a functional group on adjacent carbon atoms.
      Our calculations are consistent with the conclusion that the main role of AdoCbl
      is to provide a source of radicals, thus moving the 1,2-rearrangements onto the
      radical potential energy surface. Our studies also show that the radical
      rearrangement step is facilitated by partial proton transfer involving the
      substrate. Specifically, we observe that the energy requirements for radical
      rearrangement are reduced dramatically with appropriate partial protonation or
      partial deprotonation or sometimes (synergistically) both. Such interactions are
      particularly relevant to enzyme catalysis, because it is likely that the local
      amino acid environment in the active site of an enzyme can function in this
      capacity through hydrogen bonding. Finally, our calculations indicate that the
      intervention of a very stable radical along the reaction pathway may inactivate
      the enzyme, demonstrating that sustained catalysis depends on a delicate energy
      balance. Radical-based enzyme reactions are often difficult to probe
      experimentally, so theoretical investigations have a particularly valuable role
      to play in their study. Our research demonstrates that a small-model approach can
      provide important and revealing insights into the mechanism of action of AdoCbl
      dependent enzymes.

PMID- 20136161
TI  - Bifunctional hydrogen bonds in monohydrated cycloether complexes.
AB  - In this work, the cooperative effects implicated in bifunctional hydrogen bonds
      (H-bonds) were studied (in monohydrated six-membered cycloether) within the
      framework of the atoms in molecules (AIM) theory and of the natural bond orbitals
      (NBO) analysis. The study was carried out in complexes formed by six-membered
      cycloether compounds (tetrahydropyrane, 1,4-dioxane, and 1,3-dioxane) and a water
      molecule. These compounds were used as model systems instead of more complicated
      molecules of biological importance. All the results were obtained at the second
      order Moller-Plesset (MP2) level theory using a 6-311++G(d,p) basis set.
      Attention was focused on the indicators of the cooperative effects that arise
      when a water molecule interacts simultaneously with a polar and a nonpolar
      portion of a six-membered cycloether (via bifunctional hydrogen bonds) and
      compared with conventional H-bonds where the water molecule only interacts with
      the polar portion of the cycloether. Different indicators of H-bonds strength,
      such as structural and spectroscopic data, electron charge density, population
      analysis, hyperconjugation energy and charge transference, consistently showed
      significant cooperative effects in bifunctional H-bonds. From the AIM, as well as
      from the NBO analysis, the obtained results allowed us to state that in the
      monohydrated six-membered cycloether, where the water molecule plays a dual role,
      as proton acceptor and proton donor, a mutual reinforcement of the two
      interactions occurs. Because of this feature, the complexes engaged by
      bifunctional hydrogen bonds are more stabilized than the complexes linked by
      conventional hydrogen bonds.

PMID- 20136162
TI  - Aqueous aerosol may build up an elevated upper tropospheric ice supersaturation
      and form mixed-phase particles after freezing.
AB  - Observations often reveal large clear-sky upper tropospheric ice supersaturation,
      S(i), which sometimes reaches 100%. However, a water activity criterion (Nature
      2000, 406, 611) does not allow the buildup of large S(i) by cooled aqueous
      aerosol. According to the criterion, S(i) produced by aqueous aerosol increases
      from approximately 52% at 220 K to only approximately 67% at 185 K. The nature of
      the formation of large upper tropospheric S(i) remains unclear. Here we present
      the results of the study of micrometer-scaled three-, four-, and five-component
      droplets containing different weight fractions of H(2)O, H(2)SO(4), HNO(3),
      (NH(4))(2)SO(4), (NH(4))HSO(4), NH(4)NO(3), and (NH(4))(3)H(SO(4))(2). The study
      was performed between 133 and 278 K at cooling rates of 3, 0.1, and 0.05 K/min
      using differential scanning calorimetery. We find that complex phase
      transformations, which include one, two, and three freezing and melting events,
      glass transition on cooling, and devitrification and crystallization-freezing on
      warming, can occur during the cooling and warming of droplets. Using the measured
      freezing temperature of ice, T(i), and the thermodynamic E-AIM model, we
      calculate the largest clear-sky S(i) which would be formed immediately prior to
      the formation of ice cirrus by homogeneous freezing of multicomponent aerosol.
      The calculations show that multicomponent aerosol of some compositions may
      produce S(i) >80% at temperatures higher than 185 K. We also find that similar to
      that of H(2)SO(4)/H(2)O and H(2)SO(4)/HNO(3)/H(2)O aerosol the freezing of
      multicomponent aerosol can also produce mixed-phase cirrus particles: an ice core
      + a residual solution coating.

PMID- 20136163
TI  - Theoretical study on the reaction mechanism between 6-benzyl-6
      azabicyclo[2.2.1]hept-2-ene and benzoyl isocyanate to urea and isourea.
AB  - Reaction mechanisms of the 6-benzyl-6-azabicyclo[2.2.1]hept-2-ene with benzoyl
      isocyanate have been investigated using density functional theory (DFT) at the
      B3LYP/6-31G(d,p) level of theory. The reaction proceeding along six competitive
      channels includes two categories. That is, two channels are formally [3,3]
      sigmatropic rearrangements and four channels are [4+2] cycloadditions. For urea,
      the formally [3,3]-sigmatropic rearrangement channel and the [4+2] cycloaddition
      channels are competitive since they have similar barriers. However, the [4+2]
      cycloaddition channels are energetically favorable pathways to lead to isourea,
      with the highest barrier of 12.77 kcal/mol. These polar Diels-Alder (P-DA)
      reactions are controlled by the charge transfer (CT) at the transition states.
      Moreover, the main products of this reaction include urea and isourea.
      Furthermore, difference of two new bond lengths at transition states indicate
      that the [4+2] cycloadditions in this reaction are asynchronous processes, which
      is in good agreement with the experiment.

PMID- 20136164
TI  - Efficacy and safety of fenofibric acid co-administered with low- or moderate-dose
      statin in patients with mixed dyslipidemia and type 2 diabetes mellitus: results
      of a pooled subgroup analysis from three randomized, controlled, double-blind
      trials.
AB  - BACKGROUND: Monotherapy with lipid-modifying medication is frequently
      insufficient to normalize lipid abnormalities in patients with mixed dyslipidemia
      and type 2 diabetes mellitus. OBJECTIVE: To evaluate the efficacy and safety of
      fenofibric acid + statin combination therapy in this population. STUDY DESIGN: A
      pooled, subgroup analysis of three randomized, controlled, double-blind, 12-week
      trials. SETTING: Multiple clinical research facilities in the US and Canada.
      PATIENTS: Patients with mixed dyslipidemia and type 2 diabetes (n = 586).
      INTERVENTION: Fenofibric acid (Trilipix) 135 mg monotherapy; low-, moderate-, or
      high-dose statin monotherapy (rosuvastatin [Crestor] 10, 20, or 40 mg;
      simvastatin [Zocor] 20, 40, or 80 mg; or atorvastatin [Lipitor] 20, 40, or 80
      mg); or fenofibric acid + low- or moderate-dose statin. MAIN OUTCOME MEASURE:
      Mean percentage changes in lipid parameters, percentages of patients achieving
      optimal serum lipid/apolipoprotein levels, and incidence of adverse events.
      RESULTS: Fenofibric acid + low-dose statin resulted in significantly (p < 0.001)
      greater mean percentage changes in high-density lipoprotein cholesterol (HDL-C)
      [16.8%] and triglycerides (-43.9%) than low-dose statin monotherapy (4.7% and 
      18.1%, respectively) and significantly (p < 0.001) greater reductions in low
      density lipoprotein cholesterol (LDL-C) [-34.0%] than fenofibric acid monotherapy
      (-5.3%). Similarly, fenofibric acid + moderate-dose statin resulted in
      significantly (p < or = 0.011) greater mean percentage changes in HDL-C (16.3%)
      and triglycerides (-43.4%) than moderate-dose statin monotherapy (8.7% and 
      24.2%, respectively) and significantly (p < 0.001) greater reductions in LDL-C (
      32.6%) than fenofibric acid monotherapy (-5.3%). Compared with low- or moderate
      dose statin, fenofibric acid + low- or moderate-dose statin resulted in over 5
      fold higher percentages of patients achieving optimal levels of LDL-C, non-HDL-C,
      apolipoprotein B, HDL-C, and triglycerides simultaneously. Incidence of adverse
      events was generally similar among treatments. CONCLUSION: Fenofibric acid +
      statin combination therapy in patients with mixed dyslipidemia and type 2
      diabetes was well tolerated and resulted in more comprehensive improvement in the
      lipid/apolipoprotein profile than either monotherapy. [Clinical trials are
      registered at www.clinicaltrials.gov: NCT00300482, NCT00300456, and NCT00300469].

PMID- 20136165
TI  - Development of CRIteria to assess appropriate Medication use among Elderly
      complex patients (CRIME) project: rationale and methodology.
AB  - Pharmacological treatment of complex older adults with comorbidities, multiple
      impairments in function, cognition, social status and geriatric syndromes
      represents a challenge for prescribing physicians and often results in a high
      rate of iatrogenic illnesses. Clinical guidelines are commonly used to indicate
      appropriate prescription, but they are often based on the results of clinical
      trials that are conducted on young subjects with a low level of complexity.
      Therefore, the recommendations of clinical guidelines may be difficult to apply
      to older complex adults. In this paper we present the rationale and methodology
      of the Development of CRIteria to assess appropriate Medication use among Elderly
      complex patients (CRIME) project, a study aimed at producing recommendations to
      evaluate the appropriateness of pharmacological prescription in older complex
      patients, translating the recommendations of clinical guidelines to this type of
      patient. A literature search will be performed to integrate and revise the
      recommendations of disease-specific guidelines on the pharmacological treatment
      of patients with common chronic conditions. New recommendations will be provided
      and approved in a consensus meeting of international experts. Both data from
      randomized controlled trials and observational studies will be used to meet this
      aim. Recommendations provided by the CRIME project are not meant to replace
      existing clinical guidelines, but they may be used to help physicians in the
      prescribing process. Once completed these recommendations should be validated in
      interventional studies.

PMID- 20136166
TI  - Inappropriate drug prescriptions among older nursing home residents: the Italian
      perspective.
AB  - Older people take up a large proportion of health care, including drugs, and
      evidence shows that drug prescribing to this group is often inappropriate.
      Negative consequences of potential inappropriate drug prescription (PIDP) include
      adverse drug events, high healthcare service utilization and high costs for the
      patients and society. Although nursing home residents are the most vulnerable
      persons exposed to PIDP, few observational studies have investigated the
      prevalence, the factors associated with and the consequences of PIDP.
      Epidemiological studies assessing PIDP mainly based on the Beers' criteria showed
      that approximately half of US and Canadian nursing home residents have at least
      one PIDP in this setting. The most frequent inappropriate prescriptions concern
      neuroleptics and long-term benzodiazepines. Nursing home residents aged 80 years
      or more, those taking a low number of drugs, cognitive or communication problems
      are less exposed to PIDP compared with residents younger than 80 years, living in
      facilities with a high number of beds and a lower registered nurse-to-resident
      ratio. In European countries, the prevalence of PIDP among older nursing home
      residents was comparable to or higher than that observed in US and Canadian
      nursing homes. To date, the issue of PIDP has never been investigated in a
      representative sample of Italian nursing home residents. In a preliminary study
      performed by our group in 496 nursing home residents randomly selected from 40
      nursing homes in Umbria, the prevalence of residents taking at least one or two
      inappropriate medications was 28% and 7%, respectively. The prevalence of PIDP
      considering diagnosis (18%) as well as those regardless of diagnosis (17%), as
      determined by Beers' criteria, were equally distributed in older Italian nursing
      home residents and no difference was found between sexes. Overall, this review
      reveals that the prevalence of PIDP is high in both North American and European
      nursing homes and highlights the urgent need for intervention trials testing
      strategies to reduce the health and social burden of PIDP.

PMID- 20136167
TI  - Potentially inappropriate medication in elderly hospitalized patients.
AB  - Balanced and safe prescribing is difficult to achieve in frail older adults with
      multiple comorbid diseases. This issue is of particular concern, especially in
      elderly hospitalized patients because hospitalization exposes such individuals to
      an increased risk of adverse drug reactions (ADRs). The avoidance of medications
      that are considered to be inappropriate is among the interventions for treatment
      options in elderly patients. A potentially inappropriate medication (PIM) is a
      drug in which the risk of an adverse event outweighs its clinical benefit,
      particularly when there is a safer or more effective alternative therapy for the
      same condition. Explicit criteria have been developed to identify PIMs and among
      these, Beers' criteria are the most frequently applied in the literature.
      However, evidence suggests that such criteria cannot easily be applied to elderly
      hospitalized people in European countries; approximately 20% of drugs listed in
      Beers' criteria are rarely prescribed or are not available in Europe, and Beers'
      listed PIMs are not associated with inhospital mortality, length of hospital stay
      and/or ADRs in Italian studies. On the contrary, ADRs can contribute to
      accelerated functional decline in elderly hospitalized patients independently of
      the use of Beers' listed PIMs. Therefore, we will review the evidence pertaining
      to the application of Beers' criteria in elderly hospitalized patients, while
      focusing on Italian studies that have investigated the role of PIMs as potential
      predictors of negative hospital outcomes. In addition, we will also review the
      available evidence regarding new European criteria on identifying PIMs, because
      clinical application in elderly hospitalized Europeans is still under
      investigation.

PMID- 20136168
TI  - Variability in the prescription of cardiovascular medications in older patients:
      correlates and potential explanations.
AB  - In western countries approximately a quarter of the population is 65 years and
      older. People in this age group often have several coexisting medical problems
      and take multiple drugs, and older people receive the greatest proportion of
      dispensed prescriptions. The prevalence of cardiovascular diseases, the leading
      cause of death and a major cause of physical and cognitive disability, increases
      steeply with increasing age. Drugs for the prevention and treatment of
      cardiovascular conditions account for a large proportion of medication
      prescription in older persons. Despite a number of published guidelines and
      expert recommendations supporting a standardized use of many cardiovascular
      agents, there is growing evidence of a tremendous variability in cardiovascular
      drug prescriptions according to demographics, health characteristics, and setting
      of care. In particular, evidence shows an inverse relationship between treatment
      propensity and age. To date, there is little evidence of benefit of most
      pharmacotherapy in frail, older subjects or elderly individuals with multiple
      comorbidities and polypharmacotherapy. However, effective treatment should not be
      denied solely on the basis of age. A major challenge in geriatric practice is to
      ensure safe and effective pharmacological treatments, avoiding the risk of
      polypharmacy and inappropriate drug prescription.

PMID- 20136169
TI  - Antidiabetic oral treatment in older people: does frailty matter?
AB  - Life expectancy has significantly increased over the past 30 years, with a
      greater prevalence of diverse disease states, especially type 2 diabetes
      mellitus. As older persons are a very heterogeneous group with an increased
      prevalence of comorbidities and a relative inability to tolerate the adverse
      effects of oral antidiabetic agents, the treatment of type 2 diabetes is
      particularly demanding. The principles of its management are similar to those in
      younger patients, but with special considerations linked to comorbidities and
      clinical status. The available oral antidiabetic drugs include insulin
      secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha
      glucosidase inhibitors, thiazolidinediones and newly introduced inhibitors of
      glucagon-like peptide 1 degrading enzyme dipeptidyl peptidase 4 (DPP-4). In
      addition, clinical aspects complicate diabetes care in the elderly, including
      cognitive disorders, physical disability and geriatric syndromes, such as
      frailty. The European Diabetes Working Party for Older Persons has increased
      glycaemic recommendations for target haemoglobin A(1c) from <7% to <or=8% in the
      presence of frailty. This working party updated their guidelines in 2008 and
      their aim is to ensure that older Europeans with type 2 diabetes have high
      quality diabetes care throughout their lives. The working party has created
      guidelines for the use of many drugs, and we will discuss some of these
      guidelines on the use of oral antidiabetic agents and their importance in the
      presence of frailty. Furthermore, as type 2 diabetes progresses in older persons,
      polypharmacy intensification is usually required to reach adequate glycaemic
      control, with the risk of adverse effects. In particular, clinical evidence shows
      that the use of sulfonylureas is associated with a greater risk of
      hypoglycaemica, whereas metformin and alpha-glucosidase inhibitors are associated
      with an increased risk of adverse gastrointestinal effects. The adverse effects
      of the recently introduced DPP-4 inhibitors are nasopharyngitis and/or upper
      respiratory tract infections. The literature suggests that oral antidiabetic
      agents are suitable for older persons; however, underappreciated risk factors,
      such as cognitive decline in frail individuals, have an important impact on oral
      antidiabetic treatment options.

PMID- 20136170
TI  - Opioids for the treatment of chronic non-cancer pain in older people.
AB  - Chronic pain occurs in 45-85% of the geriatric population and the need to treat
      chronic pain is growing substantially. Unfortunately, treatment for chronic pain
      is not always correctly targeted, which leads to a reduced quality of life, with
      decreased socialization, depression, sleep disturbances, cognitive impairment,
      disability and malnutrition. Considering these consequences, healthcare
      professionals should aim at improving the diagnosis and treatment of chronic pain
      in older persons. One of the most important limitations in achieving successful
      pain management is that older people are not aware that pain management options
      exist or medications for pain, such as opioids, have associated benefits and
      adverse effects. Importantly, opioids do not induce any organ failure and if
      adequately used at the right dosage may only present some predictable and
      preventable adverse effects. Treating and controlling chronic pain is essential
      in elderly patients in order to maintain a good quality of life and an active
      role in both the family and society. To date there are only a few randomized
      clinical trials testing opioid therapy in elderly patients, and the aim of the
      present review is to highlight the efficacy and tolerability of opioid use
      through a literature search strategy in elderly people with chronic non-cancer
      pain.

PMID- 20136172
TI  - Drugs Aging. Conclusions.

PMID- 20136171
TI  - Pharmacoeconomics and aging.
AB  - The aging of the general population in industrialized countries has brought to
      public attention the increasing incidence of age-related clinical conditions,
      because the long-term impact of diseases on functional status and on costs are
      greater in older people than in any other age group. With the aging of the
      population, it is becoming increasingly important to quantify the burden of
      illness in the elderly; this will be vital not only in planning for the necessary
      health services that will be required in coming years, but also in order to
      measure the benefit to be expected from interventions to prevent disability in
      older people. The management of multiple and chronic disorders has become a more
      important issue for healthcare authorities because of increasing requests for
      medical assistance and healthcare interventions. Among these, pharmacological
      treatments and drug utilization in older people are pressing issues for
      healthcare managers and politicians; indeed, a relatively small proportion of the
      population accounts for a substantial part of public drug costs. Two key sources
      of pressure are well known: the growing number of elderly persons, who are the
      highest per-capita users of medicines, and the introduction of new, often more
      expensive, medicines. On the other hand, the development of strategies for
      controlling costs, while providing the elderly with equitable access to needed
      pharmaceuticals, should be based on an evaluation of the economic impact of
      pharmacological care in older people, taking into account the burden of illness,
      drug utilization data, drug technology assessment evidence and results.
      Furthermore, there are major factors affecting pharmacological care in older
      people: for example inappropriate prescribing, lack of adherence and compliance,
      and the burden of adverse drug events. The assessment of these factors should be
      considered a priority in pharmacoeconomic evaluations in the aging population,
      and the most relevant evidence will be reviewed in this paper with examples
      referring to particular settings or conditions and diseases, such as the presence
      of cardiovascular risk factors, diabetes and chronic pain.

PMID- 20136173
TI  - Crosstalk mitigation using adaptive time reversal.
AB  - Although the spatial focusing property of the conventional time reversal approach
      facilitates multiuser communications, there always is residual crosstalk between
      users. A recent paper [Kim and Shin, J. Acoust. Soc. Am. 115, 600-606 (2004)]
      proposed an adaptive active time reversal approach for simultaneous multiple
      focusing with minimal interference. This letter applies the adaptive approach to
      passive time reversal, multiuser communications for additional suppression of
      crosstalk among users. Experimental data at 3.5 kHz with a 1-kHz bandwidth
      demonstrate as much as 6.5-dB improvement per user in terms of output signal-to
      noise ratio for three-user communications over a 20-km range in 120-m deep
      shallow water.

PMID- 20136174
TI  - Effects of stimulus duration on amplitude modulation processing with cochlear
      implants.
AB  - This study investigated temporal integration processes underlying cochlear
      implant (CI) users' amplitude modulation processing. Thresholds for modulation
      detection (AMDTs) and modulation frequency discrimination (AMFDTs) were measured
      for 50-, 100-, and 200-Hz modulation frequencies with stimulus durations from 50
      to 400 ms in eight adult CI users. The results showed significant interactions
      between modulation frequency and stimulus duration for AMDTs and AMFDTs. The data
      suggest that temporal integration limits CI users' sensitivity to low temporal
      pitch over short durations, and that temporal integration over longer durations
      may not enhance CI users' sensitivity to high temporal pitch.

PMID- 20136175
TI  - A simple method to account for size effects in the transfer matrix method.
AB  - The transfer matrix method based is extensively used and well-validated for
      predicting the transmission loss of multilayer structures. However, this method
      leads to poor results at low frequencies due to the infinite extent assumption it
      is based on. This paper presents an efficient implementation of a Rayleigh
      integral based method to account for the finite size effects. The accuracy of the
      method is illustrated by various examples.

PMID- 20136176
TI  - Recognition of interrupted sentences under conditions of spectral degradation.
AB  - Cochlear implant (CI) and normally hearing (NH) listeners' recognition of
      periodically interrupted sentences was investigated. CI listeners' scores
      declined drastically when the sentences were interrupted. The NH listeners showed
      a significant decline in performance with increasing spectral degradation using
      CI-simulated, noise-band-vocoded speech. It is inferred that the success of top
      down processes necessary for the perceptual reconstruction of interrupted speech
      is limited by even mild degradations of the bottom-up information stream (16 and
      24 band processing). A hypothesis that the natural voice-pitch variations in
      speech would help in the perceptual reconstruction of the sentences was not
      supported by experimental results.

PMID- 20136177
TI  - Ray-based blind deconvolution in ocean sound channels.
AB  - This letter describes a ray-based blind deconvolution technique for ocean sound
      channels that produces broadband estimates of the source-to-array impulse
      response and the original source waveform from array-measured signals corrupted
      by (unknown) multipath propagation. The technique merely requires elementary
      knowledge of array geometry and sound speed at the array location. It is based on
      identifying a ray arrival direction to separate source waveform and acoustic
      propagation phase contributions to the received signals. This technique
      successfully decoded underwater telecommunication sequences in the bandwidth 3-4
      kHz that were broadcast 4 km in a 120-m-deep ocean sound channel without a-priori
      knowledge of sound channel characteristics.

PMID- 20136178
TI  - Structural damage identification in plates via nonlinear structural intensity
      maps.
AB  - A nonlinear structural intensity concept is presented as an approach for the
      identification of defects displaying nonlinear vibration behavior. The nonlinear
      structural dynamic response exhibited by a riveted joint with loosened fasteners
      connecting a stiffener with a flat panel is investigated. The excitation,
      generating elastic waves with dominant bending components, triggers the nonlinear
      contact between the plate and the stiffener inducing a dynamic response rich with
      nonlinear harmonics. Experimental structural intensity maps are evaluated at the
      super-harmonic frequencies. This technique provides an experimental approach for
      the characterization and two dimensional visualization of nonlinear types of
      defects.

PMID- 20136179
TI  - Orienting attention during phonetic training facilitates learning.
AB  - The role of consciously directed attention toward speech input in learning has
      not yet been determined. Previous phonetic learning studies have manipulated
      acoustic signals and response feedback, but not conscious control over
      attentional orienting. This study tests whether directed attention facilitates
      learning of phonetic information. Two monolingual English-speaking groups were
      trained with feedback on the same auditory stimuli: Hindi words. One group was
      instructed to attend to the consonants and the other to the vowels. The consonant
      oriented group, but not the vowel-oriented group, demonstrated post-training
      improvement in consonant perception, confirming a role for consciously directed
      attentional mechanisms during phonetic learning.

PMID- 20136180
TI  - The neural code for interaural time difference in human auditory cortex.
AB  - A magnetoencephalography study was conducted to reveal the neural code of
      interaural time difference (ITD) in the human cortex. Widely used crosscorrelator
      models predict that the code consists of narrow receptive fields distributed to
      all ITDs. The present findings are, however, more in line with a neural code
      formed by two opponent neural populations: one tuned to the left and the other to
      the right hemifield. The results are consistent with models of ITD extraction in
      the auditory brainstem of small mammals and, therefore, suggest that similar
      computational principles underlie human sound source localization.

PMID- 20136181
TI  - Verification of a near-field error sensor placement method in active control of
      compact noise sources.
AB  - Recent experiments in active noise control (ANC) have used near-field error
      sensors whose locations are determined according to the minimization of sound
      power. Sensors should be placed in regions where the sound pressure reductions
      are the greatest during sound power minimization of the ANC system. Near-field
      pressure measurements of noise sources with and without ANC were made. With the
      error sensors in theoretically ideal locations, the measured near-field pressure
      map approximates the theoretical map created under the condition of minimized
      radiated power. Moving the error sensors to theoretically nonideal locations
      greatly reduces the attenuation of radiated sound power.

PMID- 20136182
TI  - Auditory-model based robust feature selection for speech recognition.
AB  - It is shown that robust dimension-reduction of a feature set for speech
      recognition can be based on a model of the human auditory system. Whereas
      conventional methods optimize classification performance, the proposed method
      exploits knowledge implicit in the auditory periphery, inheriting its robustness.
      Features are selected to maximize the similarity of the Euclidean geometry of the
      feature domain and the perceptual domain. Recognition experiments using mel
      frequency cepstral coefficients (MFCCs) confirm the effectiveness of the
      approach, which does not require labeled training data. For noisy data the method
      outperforms commonly used discriminant-analysis based dimension-reduction methods
      that rely on labeling. The results indicate that selecting MFCCs in their natural
      order results in subsets with good performance.

PMID- 20136183
TI  - A non-linear three-dimensional model for quantifying microbubble dynamics.
AB  - A three-dimensional non-linear model for simulating microbubble response to
      acoustic insonation is presented. A 1 mum radius microbubble stimulated using
      positive and inverted 2.4 MHz pulses produced radius-time curves that matched
      (error <10%) with the experimental observation. A bound 2.3 mum radius
      microbubble insonated using 2.25 MHz 6 cycle pulse was observed to oscillate with
      max/min oscillations 45% lower than that of the free microbubble, this correlated
      ( approximately 10% error) with the observations of Garbin et al. [Appl. Phys.
      Lett. 90, 114103 (2007)]. The adherent microbubble oscillated asymmetrically in
      the plan view and symmetrically in the elevation view, consistent with the
      previous experimental results.

PMID- 20136184
TI  - Scattering by an arrangement of eccentric cylinders embedded on a coated cylinder
      with applications to tomographic density imaging.
AB  - The solution to the scattering of an incident pressure wave by an arrangement of
      eccentric cylinders embedded inside a pair of concentric cylinders is derived
      here using a combination of T-matrix and mode-matching approaches. This method
      allows the generation of synthetic data from relatively complex structures to be
      used for the validation of acoustic tomography methods. An application of the
      solution derived here is illustrated by reconstructing sound speed and density
      profiles from a complex phantom using inverse scattering.

PMID- 20136185
TI  - Theoretical model for the threshold onset of contrast microbubble oscillations.
AB  - It has been reported recently through high speed optical observations of
      phospholipid-coated contrast microbubbles that there is a threshold value for the
      acoustic pressure amplitude below which the radial oscillation of the
      microbubbles does not occur. In this Letter, it is suggested that this threshold
      behavior results from the fact that a phospholipid layer, as a physical material,
      has a certain value of the limiting shear stress so that its deformation does not
      start until this limiting value is exceeded. A theoretical model is proposed for
      the description of this phenomenon. The model explains the experimentally
      observed dependence of the threshold onset of microbubble oscillation on the
      initial bubble radius.

PMID- 20136186
TI  - The influence on predicted harmonic and distortion product generation of the
      position of the nonlinearity within cochlear micromechanical models.
AB  - Numerical techniques are used to explore the influence on the predicted basilar
      membrane (BM) response of the position of the nonlinearity within the
      micromechanical feedback loop of an active nonlinear cochlear model. This
      position is found to influence both the harmonic and distortion product spectra
      of the predicted BM response. The BM motion at the fundamental or primary
      frequencies is not significantly altered by the position of the nonlinearity,
      however, provided that the gain is appropriately adjusted. The observed effects
      are explained in terms of the frequency responses of the elements within the
      micromechanical feedback loop.

PMID- 20136187
TI  - Modulation rate discrimination using half-wave rectified and sinusoidally
      amplitude modulated stimuli in cochlear-implant users.
AB  - Detection and modulation rate discrimination were measured in cochlear-implant
      users for pulse-trains that were either sinusoidally amplitude modulated or were
      modulated with half-wave rectified sinusoids, which in acoustic hearing have been
      used to simulate the response to low-frequency temporal fine structure. In
      contrast to comparable results from acoustic hearing, modulation rate
      discrimination was not statistically different for the two stimulus types. The
      results suggest that, in contrast to binaural perception, pitch perception in
      cochlear-implant users does not benefit from using stimuli designed to more
      closely simulate the cochlear response to low-frequency pure tones.

PMID- 20136188
TI  - The scattering of sound by a long cylinder above an impedance boundary.
AB  - The classical problem of sound scattering by an acoustically hard cylinder due to
      a point monopole and a line airborne source is extended in the present study. The
      solution to the homogeneous Helmholtz equation is expressed in a cylindrical
      coordinate system and represented by an expansion of Fourier integrals.
      Incorporating the image source method and the Bessel function addition theorem,
      the analytical solution is derived for the prediction of multiple scattering of
      sound by a hard cylinder placed above a ground surface of finite impedance. The
      total sound field can be expressed as a sum of four components: the incident
      field, the reflected wave, and the scattered fields from the cylinder and its
      image. The total far-field scattered potential was evaluated asymptotically by
      the method of stationary phase. Experimental measurements by using a point source
      were conducted in an anechoic chamber to validate the theoretical formulations.
      The numerical predictions of using a point source model give good agreements with
      all the experimental data but there are obvious discrepancies in the spectral
      magnitudes between the calculation and experimental results when a line source
      model is used to simulate the scattering problem due to a point source
      excitation.

PMID- 20136189
TI  - A residual-potential boundary for time-dependent, infinite-domain problems in
      computational acoustics.
AB  - A theoretically exact computational boundary is introduced, that is based on
      modal residual potentials for the spherical geometry. The boundary produces a set
      of first-order, uncoupled ordinary differential equations for nodal boundary
      responses, and a set of uncoupled time-stepping equations for modal boundary
      responses. The two sets are coupled through nodal-modal transformation based on
      the orthogonal surface functions for the spherical boundary. Numerical results
      generated with the boundary are presented for a step-wave-excited, elastic,
      spherical shell submerged in an infinite acoustic medium. Extension of the method
      to other separable geometries for partial differential equations defined in
      unbounded domains is mentioned.

PMID- 20136190
TI  - Nonlinear reflection of shock shear waves in soft elastic media.
AB  - For fluids, the theoretical investigation of shock wave reflection has a good
      agreement with experiments when the incident shock Mach number is large. But when
      it is small, theory predicts that Mach reflections are physically unrealistic,
      which contradicts experimental evidence. This von Neumann paradox is investigated
      for shear shock waves in soft elastic solids with theory and simulations. The
      nonlinear elastic wave equation is approximated by a paraxial wave equation with
      a cubic nonlinear term. This equation is solved numerically with finite
      differences and the Godunov scheme. Three reflection regimes are observed. Theory
      is developed for shock propagation by applying the Rankine-Hugoniot relations and
      entropic constraints. A characteristic parameter relating diffraction and non
      linearity is introduced and its theoretical values are shown to match numerical
      observations. The numerical solution is then applied to von Neumann reflection,
      where curved reflected and Mach shocks are observed. Finally, the case of weak
      von Neumann reflection, where there is no reflected shock, is examined. The
      smooth but non-monotonic transition between these three reflection regimes, from
      linear Snell-Descartes to perfect grazing case, provides a solution to the
      acoustical von Neumann paradox for the shear wave equation. This transition is
      similar to the quadratic non-linearity in fluids.

PMID- 20136191
TI  - Nonlinear Biot waves in porous media with application to unconsolidated granular
      media.
AB  - The nonlinear propagation through porous media is investigated in the framework
      of Biot theory. For illustration, and considering the current interest for the
      determination of the elastic properties of granular media, the case of nonlinear
      propagation in "model" granular media (disordered packings of noncohesive elastic
      beads of the same size embedded in a visco-thermal fluid) is considered. The
      solutions of linear Biot waves are first obtained, considering the appropriate
      geometrical and physical parameters of the medium. Then, making use of the method
      of successive approximations of nonlinear acoustics, the solutions for the second
      harmonic Biot waves are derived by considering a quadratic nonlinearity in the
      solid frame constitutive law (which takes its origin from the high nonlinearity
      of contacts between grains). The propagation in a semi-infinite medium with
      velocity dispersion, frequency dependent dissipation, and nonlinearity is first
      analyzed. The case of a granular medium slab with rigid boundaries, often
      considered in experiments, is then presented. Finally, the importance of mode
      coupling between solid and fluid waves is evaluated, depending on the actual
      fluid, the bead diameter, or the applied static stress on the beads. The
      application of these results to other media supporting Biot waves (porous
      ceramics, polymer foams, etc.) is straightforward.

PMID- 20136192
TI  - Acoustic microstreaming around a gas bubble.
AB  - The problem of acoustic microstreaming that develops around a gas bubble in an
      ultrasound field is considered. It is shown that the solutions obtained
      previously by Wu and Du [(1997). J. Acoust. Soc. Am. 101, 1899-1907], which are
      based on the assumption that viscous effects are essential only within a thin
      boundary layer while beyond the boundary layer the liquid can be considered to be
      inviscid, lead to a severe underestimation of the power of acoustic streaming. An
      improved theory is suggested that corrects the errors of the previous theory and
      extends its limits. The proposed theory treats the entire bulk of the liquid
      outside the bubble and the gas inside the bubble as viscous heat-conducting
      fluids. No restrictions are imposed on the size of the bubble relative to the
      viscous, thermal, and sound wavelengths in the ambient liquid and those in the
      internal gas medium. All modes of the bubble's motion (volume pulsation,
      translation, and shape oscillations) are taken into account. Expressions for the
      radial and tangential stresses produced by the acoustic streaming are also
      derived. Numerical examples for parameters of interest are presented.

PMID- 20136193
TI  - A frequency domain linearized Navier-Stokes equations approach to acoustic
      propagation in flow ducts with sharp edges.
AB  - Acoustic wave propagation in flow ducts is commonly modeled with time-domain non
      linear Navier-Stokes equation methodologies. To reduce computational effort,
      investigations of a linearized approach in frequency domain are carried out.
      Calculations of sound wave propagation in a straight duct are presented with an
      orifice plate and a mean flow present. Results of transmission and reflections at
      the orifice are presented on a two-port scattering matrix form and are compared
      to measurements with good agreement. The wave propagation is modeled with a
      frequency domain linearized Navier-Stokes equation methodology. This methodology
      is found to be efficient for cases where the acoustic field does not alter the
      mean flow field, i.e., when whistling does not occur.

PMID- 20136194
TI  - Inverse problem in anisotropic poroelasticity: drained constants from undrained
      ultrasound measurements.
AB  - Poroelastic analysis has traditionally focused on the relationship between dry
      and drained constants, which are assumed known, and the saturated or undrained
      constants, which are assumed unknown. However, there are many applications in
      this field of study for which the main measurements can only be made on the
      saturated/undrained system, and then it is uncertain what the effects of the
      fluids were on the system, since the drained constants remain a mystery. The work
      presented here shows how to deduce drained constants from undrained constants for
      anisotropic systems having symmetries ranging from isotropic to orthotropic.
      Laboratory ultrasound data are then inverted for the drained constants in three
      granular packings: one of glass beads, and two others for distinct types of more
      or less angular sand grain packings. Experiments were performed under uniaxial
      stress, which resulted in hexagonal (transversely isotropic) symmetry of the
      poroelastic response. One important conclusion from the general analysis is that
      the drained constants are uniquely related to the undrained constants, assuming
      that porosity, grain bulk modulus, and pore fluid bulk modulus are already known.
      Since the resulting system of equations for all the drained constants is linear,
      measurement error in undrained constants also propagates linearly into the
      computed drained constants.

PMID- 20136195
TI  - Scattering of the fundamental torsional mode at an axial crack in a pipe.
AB  - A quantitative study of the interaction of the T(0,1) torsional mode with an
      axial defect in a pipe is presented. The results are obtained from finite element
      simulations and experiments. The influence of the crack axial extent, depth,
      excitation frequency, and pipe circumference on the scattering is examined. It is
      found that the reflection from a defect consists of a series of the wave pulses
      with gradually decaying amplitudes. Such behavior is caused by the shear waves
      diffracting from the crack and then repeatedly interacting with the crack due to
      circumferential propagation. Time-domain reflection coefficient analysis
      demonstrates that the trend of the reflection strength for different crack
      lengths, pipe diameters, and frequencies from a through-thickness crack satisfies
      a simple normalization. The results show that the reflection coefficient
      initially increases with the crack length at all frequencies but finally reaches
      an oscillating regime. Also, at a given frequency and crack length the reflection
      decreases with the increase in pipe circumference. An additional scattering study
      of the shear wave SH(0) mode at a part-thickness notch in a plate shows that the
      reflection coefficient, when plotted against depth of the notch, increases with
      both frequency and notch depth.

PMID- 20136196
TI  - Polycrystalline gamma-plutonium's elastic moduli versus temperature.
AB  - Resonant ultrasound spectroscopy was used to measure the elastic properties of
      pure polycrystalline (239)Pu in the gamma-phase. Shear and longitudinal elastic
      moduli were measured simultaneously and the bulk modulus was computed from them.
      A smooth, linear, and large decrease in all elastic moduli with increasing
      temperature was observed. The Poisson ratio was calculated and an increase from
      0.242 at 519 K to 0.252 at 571 K was found. These measurements on extremely well
      characterized pure Pu are in agreement with other reported results where overlap
      occurs. We calculated an approximate Debye temperature Theta(D)=144 K. Determined
      from the temperature variation in the bulk modulus, gamma-Pu shows the same
      Gruneisen parameter as copper.

PMID- 20136197
TI  - Structure of phonon focusing patterns in tetragonal crystals.
AB  - A set of critical conditions for the characteristic caustic points in the phonon
      focusing patterns in tetragonal crystals is formulated. A caustic line segment in
      the focusing pattern is generally associated with either a fold or a cusp on the
      wave surface. Most of the caustic lines are symmetrical with respect to the
      principal symmetry plane and can be characterized by the caustic points at the
      centers of the caustic lines. These characteristic caustic points originated from
      inflection/parabolic points with zero in-plane/ex-plane curvature, respectively.
      By employing the Stroh formalism, the inflection/parabolic points on the slowness
      surface are studied in terms of the so-called zero-curvature transonic states.
      Since these transonic states are related to extraordinary degeneracies in the
      Stroh eigenvalue equation, the conditions for the degeneracies can be regarded as
      critical conditions for the characteristic caustic points. These conditions
      provide an overview of global structure of the phonon focusing patterns in
      tetragonal crystals. A set of caustic lines in vicinity of (001) plane is also
      investigated and exemplified.

PMID- 20136198
TI  - Mindlin plate theory for damage detection: imaging of flexural inhomogeneities.
AB  - The scattering of plate waves by localized damage or defects that can be modeled
      as flexural inhomogeneities is examined within the framework of Mindlin plate
      theory. These inhomogeneities are characterized by variations in one or more of
      the four plate-theory parameters: the bending stiffness, shear stiffness, rotary
      inertia, and transverse inertia. It is shown that the Born approximation for the
      scattered field leads to a plate-theory analog of the Fourier diffraction
      theorem, which relates the far-field scattering amplitude to the spatial Fourier
      transform of the inhomogeneity variations. The application of this result is
      illustrated by using synthetic data derived for an idealized model of a
      delamination as a flexural inhomogeneity, ignoring mode coupling effects. A
      computationally efficient implementation of the filtered back-propagation
      algorithm, based on the eigensystem of the scattering operator, is employed for
      image reconstruction. The implications for in-situ imaging of structural damage
      in plate-like structures are briefly discussed, and some directions for further
      work are indicated.

PMID- 20136199
TI  - Analytical method for the ultrasonic characterization of homogeneous rigid porous
      materials from transmitted and reflected coefficients.
AB  - A frequency domain method dedicated to the analytic recovery of the four relevant
      parameters of macroscopically homogeneous rigid frame porous materials, e.g.,
      plastic foams, at the high frequency range of the Johnson-Champoux-Allard model
      is developed and presented. The reconstructions appeal to experimental data
      concerning time domain measurements of the ultrasonic fields reflected and
      transmitted by a plate of the material at normal incidence. The effective density
      and bulk modulus of the material are first reconstructed from the frequency
      domain reflection and transmission coefficients. From the latter, the porosity,
      tortuosity, and thermal and viscous characteristic lengths are recovered. In a
      sense, the method presented herein is quite similar in the ultrasonic range, but
      also quite complementary, to the method developed by Panneton and Olny [J.
      Acoust. Soc. Am. 119, 2027-2040 (2006); 123, 814-824 (2008)] at low frequency,
      which appeal to experimental data measured in an impedance tube.

PMID- 20136200
TI  - Vector intensity reconstructions in a volume surrounding a rigid spherical
      microphone array.
AB  - A technique is described to image the vector intensity in the near field of a
      spherical array of microphones flush mounted in a rigid sphere. The spatially
      measured pressure is decomposed into Fourier harmonics in order to reconstruct
      the volumetric vector intensity outside the sphere. The theory for this
      reconstruction is developed in this paper. The resulting intensity images are
      very successful at locating and quantifying unknown exterior acoustic sources,
      ideal for application in noise control problems in interior spaces such as
      automobiles and airplanes. Arrays of varying numbers of microphones and radii are
      considered and compared and errors are computed for both theory and experiment.
      It is demonstrated that this is an ill-posed problem below a cutoff frequency
      depending on array design, requiring Tikhonov regularization below cutoff. There
      is no low frequency limit on operation, although the signal-to-noise ratio is the
      determining factor for high-spatial resolution at low frequencies. It is shown
      that the upper frequency limit is set by the number of microphones in the array
      and is independent of noise. The accuracy of the approach is assessed by
      considering the exact solution for the scattering of a point source by a rigid
      sphere. Several field experiments are presented to demonstrate the utility of the
      technique. In these experiments, the partial field decomposition technique is
      used and holograms of multiple exterior sources are separated and their
      individual volumetric intensity fields imaged. In this manner, the intensity
      fields of two uncorrelated tube sources in an anechoic chamber are isolated from
      one another and separated intensity maps are obtained from over a broad frequency
      range. In a practical application, the vector intensity field in the interior of
      an automobile cabin is mapped at the fundamental of the engine vibration using
      the rigid sphere positioned at the driver's head. The source regions contributing
      to the interior cabin noise are identified.

PMID- 20136201
TI  - Prediction of the acoustical performance of enclosures using a hybrid statistical
      energy analysis: image source model.
AB  - Enclosures are commonly used to reduce the sound exposure of workers to the noise
      radiated by machinery. Some acoustic predictive tools ranging from simple
      analytical tools to sophisticated numerical deterministic models are available to
      estimate the enclosure acoustical performance. However, simple analytical models
      are usually valid in limited frequency ranges because of underlying assumptions
      whereas numerical models are commonly limited to low frequencies. This paper
      presents a general and simple model for predicting the acoustic performance of
      large free-standing enclosures which is capable of taking into account the
      complexity of the enclosure configuration and covering a large frequency range.
      It is based on the statistical energy analysis (SEA) framework. The sound field
      inside the enclosure is calculated using the method of image sources. Sound
      transmission across the various elements of the enclosure is considered in the
      SEA formalism. The model is evaluated by comparison with existing methods and
      experimental results. The effect of several parameters such as enclosure
      geometry, panel materials, presence of noise control treatments, location of the
      source inside the enclosure, and presence of an opening has been investigated.
      The comparisons between the model and the experimental results show a good
      agreement for most of the tested configurations.

PMID- 20136202
TI  - Efficient numerical modeling of traffic noise.
AB  - An optimized method is presented for the numerical evaluation of the sound field
      generated by an incoherent line source, which is commonly used to model road and
      rail traffic noise. Two different solutions for the numerical integration over
      the line source are distinguished, a point source solution and a line source
      solution. With proper segmentation of the line source, both solutions yield
      accurate results. Special attention is paid to receiver positions close to the
      (infinite) line through the (finite) line source. At these positions,
      conventional methods give numerical errors, which occur frequently in
      calculations of large-scale noise maps of cities, employing automatically
      generated geographical input data. The problems are avoided by using the
      optimized method presented here. The method is based on a combination of angular
      segmentation and linear segmentation of the line source and can be used to
      minimize the number of point-to-point calculations for noise mapping.

PMID- 20136203
TI  - Noise-induced annoyance from transportation noise: short-term responses to a
      single noise source in a laboratory.
AB  - An experimental study was performed to compare the annoyances from civil-aircraft
      noise, military-aircraft noise, railway noise, and road-traffic noise. Two-way
      within-subjects designs were applied in this research. Fifty-two subjects, who
      were naive listeners, were given various stimuli with varying levels through a
      headphone in an anechoic chamber. Regardless of the frequency weighting network,
      even under the same average energy level, civil-aircraft noise was the most
      annoying, followed by military-aircraft noise, railway noise, and road-traffic
      noise. In particular, penalties in the time-averaged, A-weighted sound level
      (TAL) of about 8, 5, and 5 dB, respectively, were found in the civil-aircraft,
      military-aircraft, and railway noises. The reason could be clarified through the
      high-frequency component and the variability in the level. When people were
      exposed to sounds with the same maximum A-weighted level, a railway bonus of
      about 3 dB was found. However, transportation noise has been evaluated by the
      time-averaged A-weighted level in most countries. Therefore, in the present
      situation, the railway bonus is not acceptable for railway vehicles with diesel
      electric engines.

PMID- 20136204
TI  - Speech levels in meeting rooms and the probability of speech privacy problems.
AB  - Speech levels were measured in a large number of meetings and meeting rooms to
      better understand their influence on the speech privacy of closed meeting rooms.
      The effects of room size and number of occupants on average speech levels, for
      meetings with and without sound amplification, were investigated. The
      characteristics of the statistical variations of speech levels were determined in
      terms of speech levels measured over 10 s intervals at locations inside, but near
      the periphery of the meeting rooms. A procedure for predicting the probability of
      speech being audible or intelligible at points outside meeting rooms is proposed.
      It is based on the statistics of meeting room speech levels, in combination with
      the sound insulation characteristics of the room and the ambient noise levels at
      locations outside the room.

PMID- 20136205
TI  - Interaural cross correlation in a sound field represented by spherical harmonics.
AB  - Spatial impression is an important acoustic quality of concert halls. An accepted
      objective measure for spatial impression is the interaural cross-correlation
      (IACC) coefficient. Recently, spherical microphone arrays have been studied for
      room acoustics analysis and music recordings. This study presents a theoretical
      formulation for the computation of IACC using spherical-harmonics representations
      of the sound field, as measured by spherical microphone arrays, and spherical
      harmonics representation of head-related transfer functions (HRTFs), taken from
      HRTF databases. As spherical microphone arrays typically use a finite number of
      microphones, they may not be able to capture the complete spatial information in
      a sound field. Therefore, the effect of limited spherical-harmonics order on the
      accuracy of IACC approximation using the proposed method is studied using
      simulated and measured data. The method presented in this paper can be further
      used to study the effect of limited spatial information on the spatial perception
      of sound fields.

PMID- 20136206
TI  - Boundary element analyses for sound transmission loss of panels.
AB  - The sound transmission characteristics of an aluminum panel and two composite
      sandwich panels were investigated by using two boundary element analyses. The
      effect of air loading on the structural behavior of the panels is included in one
      boundary element analysis, by using a light-fluid approximation for the eigenmode
      series to evaluate the structural response. In the other boundary element
      analysis, the air loading is treated as an added mass. The effect of the modal
      energy loss factor on the sound transmission loss of the panels was investigated.
      Both boundary element analyses were used to study the sound transmission loss of
      symmetric sandwich panels excited by a random incidence acoustic field. A
      classical wave impedance analysis was also used to make sound transmission loss
      predictions for the two foam-filled honeycomb sandwich panels. Comparisons
      between predictions of sound transmission loss for the two foam-filled honeycomb
      sandwich panels excited by a random incidence acoustic field obtained from the
      wave impedance analysis, the two boundary element analyses, and experimental
      measurements are presented.

PMID- 20136207
TI  - The improvement of a simple theoretical model for the prediction of the sound
      insulation of double leaf walls.
AB  - This paper presents a revised theory for predicting the sound insulation of
      double leaf cavity walls that removes an approximation, which is usually made
      when deriving the sound insulation of a double leaf cavity wall above the
      critical frequencies of the wall leaves due to the airborne transmission across
      the wall cavity. This revised theory is also used as a correction below the
      critical frequencies of the wall leaves instead of a correction due to Sewell
      [(1970). J. Sound Vib. 12, 21-32]. It is found necessary to include the "stud"
      borne transmission of the window frames when modeling wide air gap double glazed
      windows. A minimum value of stud transmission is introduced for use with
      resilient connections such as steel studs. Empirical equations are derived for
      predicting the effective sound absorption coefficient of wall cavities without
      sound absorbing material. The theory is compared with experimental results for
      double glazed windows and gypsum plasterboard cavity walls with and without sound
      absorbing material in their cavities. The overall mean, standard deviation,
      maximum, and minimum of the differences between experiment and theory are -0.6
      dB, 3.1 dB, 10.9 dB at 1250 Hz, and -14.9 dB at 160 Hz, respectively.

PMID- 20136208
TI  - A mesh-free approach to acoustic scattering from multiple spheres nested inside a
      large sphere by using diagonal translation operators.
AB  - A multiple-scattering approach is presented to compute the solution of the
      Helmholtz equation when a number of spherical scatterers are nested in the
      interior of an acoustically large enclosing sphere. The solution is represented
      in terms of partial-wave expansions, and a linear system of equations is derived
      to enforce continuity of pressure and normal particle velocity across all
      material interfaces. This approach yields high-order accuracy and avoids some of
      the difficulties encountered when using integral equations that apply to surfaces
      of arbitrary shape. Calculations are accelerated by using diagonal translation
      operators to compute the interactions between spheres when the operators are
      numerically stable. Numerical results are presented to demonstrate the accuracy
      and efficiency of the method.

PMID- 20136209
TI  - Prosodic peak estimation under segmental perturbations.
AB  - Despite the apparent simplicity, measuring the position of peaks in speech
      fundamental frequency (f(0)) can produce unexpected results in a model where f(0)
      is the superposition of a supersegmental component and a segmental component. In
      these models, the measured f(0) peak position can be as much as an entire
      syllable different from the peak of the intonation component. This difference can
      be large enough so that the measured peak positions could falsely suggest a
      phonological distinction in the intonation where none really exists. This paper
      then discusses measurement techniques that are less sensitive to segmental
      effects than directly measuring the position of the f(0) maximum. A algorithm,
      called the "bracketed maximum," is presented. The performance of these techniques
      is compared on a corpus of speech data where the intonation is expected to be in
      a stable position. The bracketed maximum can reduce the variance of peak position
      measurements by at least 15%, in the presence of changing segmental structure,
      thereby presumably yielding a more accurate measurement of the intonation peak
      position.

PMID- 20136210
TI  - Acoustic censusing using automatic vocalization classification and identity
      recognition.
AB  - This paper presents an advanced method to acoustically assess animal abundance.
      The framework combines supervised classification (song-type and individual
      identity recognition), unsupervised classification (individual identity
      clustering), and the mark-recapture model of abundance estimation. The underlying
      algorithm is based on clustering using hidden Markov models (HMMs) and Gaussian
      mixture models (GMMs) similar to methods used in the speech recognition community
      for tasks such as speaker identification and clustering. Initial experiments
      using a Norwegian ortolan bunting (Emberiza hortulana) data set show the
      feasibility and effectiveness of the approach. Individually distinct acoustic
      features have been observed in a wide range of animal species, and this combined
      with the widespread success of speaker identification and verification methods
      for human speech suggests that robust automatic identification of individuals
      from their vocalizations is attainable. Only a few studies, however, have yet
      attempted to use individual acoustic distinctiveness to directly assess
      population density and structure. The approach introduced here offers a direct
      mechanism for using individual vocal variability to create simpler and more
      accurate population assessment tools in vocally active species.

PMID- 20136211
TI  - Orthogonal-like fractional-octave-band filters.
AB  - This paper addresses the design of digital fractional-octave-band filters with
      energy conservation and perfect reconstruction--i.e., whose outputs to each
      fractional-octave-band correctly sum up to the original signal and whose partial
      energies at each output correctly sum up to the overall signal energy--a
      combination of properties that cannot be met by any current design despite its
      considerable importance in many applications. A solution is devised based on the
      introduction of complex basis functions that span the outputs of the fractional
      octave bands and whose real and imaginary parts form two individually--but not
      mutually--orthogonal bases. This imposes a "partition-of-unity" condition on the
      design of the filter frequency gains such that they exactly sum up to one over
      the frequency axis. The practical implementation of the proposed solution uses
      the discrete Fourier transform, and a fast algorithm is implemented using the
      fast Fourier transform. The proposed filters are well suited to any application
      involving the post-processing of finite-energy signals. They closely match the
      international standard templates, except for a small departure at the bandedge
      frequencies which can be made arbitrarily small.

PMID- 20136212
TI  - Automatic parameter optimization in epsilon-filter for acoustical signal
      processing utilizing correlation coefficient.
AB  - epsilon-filter can reduce most kinds of noise from a single-channel noisy signal
      while preserving signals that vary drastically such as speech signals. It can
      reduce not only stationary noise but also nonstationary noise. However, it has
      some parameters whose values are set empirically. So far, there have been few
      studies to evaluate the appropriateness of the parameter settings for epsilon
      filter. This paper employs the correlation coefficient of the filter output and
      the difference between the filter input and output as the evaluation function of
      the parameter setting. This paper also describes the algorithm to set the optimal
      parameter value of epsilon-filter automatically. To evaluate the adequateness of
      the obtained parameter, the mean absolute error is calculated. The experimental
      results show that the adequate parameter in epsilon-filter can be obtained
      automatically by using the proposed method.

PMID- 20136213
TI  - Monaural sound-source-direction estimation using the acoustic transfer function
      of a parabolic reflection board.
AB  - This paper presents a sound-source-direction estimation method using only a
      single microphone with a parabolic reflection board. A simple signal-power-based
      method using a parabolic antenna has been proposed in the radar field. But the
      signal-power-based method is not effective for finding the direction of a talking
      person due to the varying power of the uttered speech signals. In this paper, the
      sound-source-direction estimation method focuses on the acoustic transfer
      function instead of the signal power. The use of the parabolic reflection board
      leads to a difference in the acoustic transfer functions of the target direction
      and the non-target directions, where the parabolic reflector and its associated
      microphone rotate together and observe the speech at each angle. The acoustic
      transfer function is estimated from the observed speech using the statistics of
      clean speech signals. Its effectiveness has been confirmed by monaural sound
      source-direction estimation experiments in a room environment.

PMID- 20136214
TI  - Deconvolution of sparse underwater acoustic multipath channel with a large time
      delay spread.
AB  - The deconvolution of multipath underwater acoustic channel with a large time
      delay spread is investigated. The channel deconvolution involves estimating the
      multipath time-delays and attenuation factors from a noisy received signal
      consisting of multiple overlapped signals. Similar to conventional deconvolution
      methods, the proposed method estimates channel impulse response based on least
      squares criterion. However, the proposed method harnesses the sparse structure of
      an underwater acoustic channel, and [script-l](1)-norm of the channel impulse
      response is adopted as the cost function to be minimized. In addition, the
      available a priori knowledge of support constraint and attenuation factor
      constraint are imposed and channel deconvolution problem is converted to a convex
      optimization problem. Instead of employing the existing standard algorithms,
      which require huge storage space and high computational complexity, a simple
      iterative algorithm for solving the optimization problem with fast convergence
      rate and low complexity is developed. The computational complexity of the
      proposed algorithm is O(N log(2)(N)) per iteration with N being the length of the
      received signal. Simulation results confirm that the proposed method provides
      better performance in terms of temporal resolution and robustness to noise
      compared with other extant multipath channel deconvolution techniques.

PMID- 20136215
TI  - A model-based approach to dispersion and parameter estimation for ultrasonic
      guided waves.
AB  - A model-based algorithm is presented that adaptively estimates in situ ultrasonic
      guided wave system parameters. Dispersion curves, propagation loss, transducer
      distances, transmitted signal, and mode weighting coefficients are estimated
      using minimal a priori information and assumptions. The five-part algorithm is
      scalable to accommodate two or more receivers and one or more propagating modes,
      provided that mode separation can be achieved prior to use of the algorithm.
      Algorithmic performance is demonstrated on signals obtained both from theoretical
      dispersion curves and finite element modeling. Quantitative performance curves
      are presented that are based on algorithmic performance from multiple simulated
      test cases with varying amounts of additive noise. Results show excellent
      agreement between estimated and actual parameters, as well as between modeled and
      received signals.

PMID- 20136216
TI  - Influence of inhibitory synaptic kinetics on the interaural time difference
      sensitivity in a linear model of binaural coincidence detection.
AB  - Temporal correlations between the sound waves arriving at the two ears are used
      to extract the azimuthal position of sound sources. Nerve cells in the mammalian
      medial superior olive (MSO) that extract these binaural correlations are
      sensitive to interaural time differences (ITDs) in the range of about 10 micros.
      These neurons receive inputs from the two ears via four pathways, two excitatory
      and two inhibitory ones. In this paper, a simple linear model is fitted to the
      frequency dependence of ITD sensitivity of MSO neurons, which is quantified by
      the two parameters, characteristic phase and characteristic delay. The fit
      parameters are the relative delays and the relative strengths of the two
      inhibitory pathways and thus specify the underlying ITD-detecting circuit
      assuming a non-Jeffress-like situation, i.e., no excitatory delay lines but phase
      locked inhibition. The fitting procedure finds the parameters of these inhibitory
      pathways such that they account for a desired frequency dependence of ITD
      sensitivity. It is found that positive characteristic delays require a finite
      amount of ipsilateral inhibition that arrives at roughly the same time as
      ipsilateral excitation as well as contralateral inhibition that lags
      contralateral excitation so much that it effectively leads excitation of the next
      cycle.

PMID- 20136217
TI  - A computer model of auditory efferent suppression: implications for the
      recognition of speech in noise.
AB  - The neural mechanisms underlying the ability of human listeners to recognize
      speech in the presence of background noise are still imperfectly understood.
      However, there is mounting evidence that the medial olivocochlear system plays an
      important role, via efferents that exert a suppressive effect on the response of
      the basilar membrane. The current paper presents a computer modeling study that
      investigates the possible role of this activity on speech intelligibility in
      noise. A model of auditory efferent processing [Ferry, R. T., and Meddis, R.
      (2007). J. Acoust. Soc. Am. 122, 3519-3526] is used to provide acoustic features
      for a statistical automatic speech recognition system, thus allowing the effects
      of efferent activity on speech intelligibility to be quantified. Performance of
      the "basic" model (without efferent activity) on a connected digit recognition
      task is good when the speech is uncorrupted by noise but falls when noise is
      present. However, recognition performance is much improved when efferent activity
      is applied. Furthermore, optimal performance is obtained when the amount of
      efferent activity is proportional to the noise level. The results obtained are
      consistent with the suggestion that efferent suppression causes a "release from
      adaptation" in the auditory-nerve response to noisy speech, which enhances its
      intelligibility.

PMID- 20136218
TI  - Properties of a nonlinear version of the stimulus-frequency otoacoustic emission.
AB  - A procedure for extracting the nonlinear component of the stimulus-frequency
      otoacoustic emission (SFOAE) is described. This nSFOAE measures the amount by
      which the cochlear response deviates from linear additivity when the input
      stimulus is doubled in amplitude. When a 4.0-kHz tone was presented alone, the
      magnitude of the nSFOAE response remained essentially constant throughout the 400
      ms duration of the tone; response magnitude did increase monotonically with
      increasing tone level. When a wideband noise was presented alone, nSFOAE
      magnitude increased over the initial 100- to 200-ms portion of the 400-ms
      duration of the noise. When the tone and the wideband noise were presented
      simultaneously, nSFOAE magnitude decreased momentarily, then increased
      substantially for about the first 100 ms and then remained strong for the
      remainder of the presentation. Manipulations of the noise bandwidth revealed that
      the low-frequency components were primarily responsible for this rising, dynamic
      response; no rising segment was seen with bandpass or highpass noise. The rising,
      dynamic nSFOAE response is likely attributable to activation of the medial
      olivocochlear efferent system. This perstimulatory emission appears to have the
      potential to provide information about the earliest stages of auditory processing
      for stimuli commonly used in psychoacoustical tasks.

PMID- 20136219
TI  - Sensitization to masked tones following notched-noise correlates with estimates
      of cochlear function using distortion product otoacoustic emissions.
AB  - Neuronal gain adaptation has been proposed as the underlying mechanism leading to
      the perception of phantom sounds such as Zwicker tones and tinnitus. In this gain
      adaptation theory, cochlear compression plays a significant role with weaker
      compression leading to stronger phantom percepts. The specific aim of this study
      was to find a link between the strength of neuronal gain adaptation and cochlear
      compression. Compression was assessed using distortion product otoacoustic
      emissions (DPOAEs). Gain adaptation is hypothesized to manifest itself in the
      sensitization observed for the detection of masked tones when preceded by notched
      noise. Perceptual thresholds for pure tones in notched noise were measured at
      multiple frequencies following various priming signals. The observed
      sensitization was larger than expected from the combined effect of the various
      maskers. However, there was no link between sensitization and compression.
      Instead, across subjects, stronger sensitization correlated with stronger DPOAEs
      evoked by low-level primaries. In addition, growth of DPOAEs correlated reliably
      with perceptual thresholds across frequencies within subjects. Together, the data
      suggest that short-term dynamic adaptation leading to perceptual sensitization is
      the result of an active process mediated by the outer hair cells, which are
      thought to modulate the gain of the cochlear amplifier via efferent feedback.

PMID- 20136220
TI  - Effects of simulated spectral holes on speech intelligibility and spatial release
      from masking under binaural and monaural listening.
AB  - The possibility that "dead regions" or "spectral holes" can account for some
      differences in performance between bilateral cochlear implant (CI) users and
      normal-hearing listeners was explored. Using a 20-band noise-excited vocoder to
      simulate CI processing, this study examined effects of spectral holes on speech
      reception thresholds (SRTs) and spatial release from masking (SRM) in difficult
      listening conditions. Prior to processing, stimuli were convolved through head
      related transfer-functions to provide listeners with free-field directional cues.
      Processed stimuli were presented over headphones under binaural or monaural
      (right ear) conditions. Using Greenwood's [(1990). J. Acoust. Soc. Am. 87, 2592
      2605] frequency-position function and assuming a cochlear length of 35 mm,
      spectral holes were created for variable sizes (6 and 10 mm) and locations (base,
      middle, and apex). Results show that middle-frequency spectral holes were the
      most disruptive to SRTs, whereas high-frequency spectral holes were the most
      disruptive to SRM. Spectral holes generally reduced binaural advantages in
      difficult listening conditions. These results suggest the importance of measuring
      dead regions in CI users. It is possible that customized programming for
      bilateral CI processors based on knowledge about dead regions can enhance
      performance in adverse listening situations.

PMID- 20136221
TI  - Median-plane sound localization as a function of the number of spectral channels
      using a channel vocoder.
AB  - Using a vocoder, median-plane sound localization performance was measured in
      eight normal-hearing listeners as a function of the number of spectral channels.
      The channels were contiguous and logarithmically spaced in the range from 0.3 to
      16 kHz. Acutely testing vocoded stimuli showed significantly worse localization
      compared to noises and 100 pulses click trains, both of which were tested after
      feedback training. However, localization for the vocoded stimuli was better than
      chance. A second experiment was performed using two different 12-channel spacings
      for the vocoded stimuli, now including feedback training. One spacing was from
      experiment 1. The second spacing (called the speech-localization spacing)
      assigned more channels to the frequency range associated with speech. There was
      no significant difference in localization between the two spacings. However, even
      with training, localizing 12-channel vocoded stimuli remained worse than
      localizing virtual wideband noises by 4.8 degrees in local root-mean-square error
      and 5.2% in quadrant error rate. Speech understanding for the speech-localization
      spacing was not significantly different from that for a typical spacing used by
      cochlear-implant users. These experiments suggest that current cochlear implants
      have a sufficient number of spectral channels for some vertical-plane sound
      localization capabilities, albeit worse than normal-hearing listeners, without
      loss of speech understanding.

PMID- 20136222
TI  - Effects of a curved vocal tract with grid-generated tongue profile on low-order
      formants.
AB  - A hyperbolic grid-generation algorithm allows investigation of the effect of
      vocal-tract curvature on low-order formants. A smooth two-dimensional (2D) curve
      represents the combined lower lip, tongue, and anterior pharyngeal wall profile
      as displacements from the combined upper lip, palate, and posterior pharyngeal
      wall outline. The algorithm is able to generate tongue displacements beyond the
      local radius of strongly curved sections of the palate. The 2D grid, along with
      transverse profiles of the lip, oral-pharyngeal, and epilarynx regions, specifies
      a vocal conduit from which an effective area function may be determined using
      corrections to acoustic parameters resulting from duct curvature; the effective
      area function in turn determines formant frequencies through an acoustic
      transmission-line calculation. Results of the corrected transmission line are
      compared with a three-dimensional finite element model. The observed effects of
      the curved vocal tract on formants F1 and F2 are in order of importance, as
      follows: (1) reduction in midline distances owing to curvature of the palate and
      the bend joining the palate to the pharynx, (2) the curvature correction to areas
      and section lengths, and (3) adjustments to the palate-tongue distance required
      to produce smooth tongue shapes at large displacements from the palate.

PMID- 20136223
TI  - Biomechanical modeling of the three-dimensional aspects of human vocal fold
      dynamics.
AB  - Human voice originates from the three-dimensional (3D) oscillations of the vocal
      folds. In previous studies, biomechanical properties of vocal fold tissues have
      been predicted by optimizing the parameters of simple two-mass-models to fit its
      dynamics to the high-speed imaging data from the clinic. However, only lateral
      and longitudinal displacements of the vocal folds were considered. To extend
      previous studies, a 3D mass-spring, cover-model is developed, which predicts the
      3D vibrations of the entire medial surface of the vocal fold. The model consists
      of five mass planes arranged in vertical direction. Each plane contains five
      longitudinal, mass-spring, coupled oscillators. Feasibility of the model is
      assessed using a large body of dynamical data previously obtained from excised
      human larynx experiments, in vivo canine larynx experiments, physical models, and
      numerical models. Typical model output was found to be similar to existing
      findings. The resulting model enables visualization of the 3D dynamics of the
      human vocal folds during phonation for both symmetric and asymmetric vibrations.

PMID- 20136224
TI  - Objective estimation of tracheoesophageal speech ratings using an auditory model.
AB  - Total laryngectomy is often the treatment of choice for many individuals
      diagnosed with advanced laryngeal cancer. This procedure alters the normal voice
      production mechanism, and tracheoesophageal (TE) speech is one alternative method
      of voicing postlaryngectomy. TE speech is created when pulmonary air is passed
      through the upper esophagus to create a vibratory source that is then articulated
      into speech. TE speech is often characterized by abnormal voice quality. Acoustic
      analysis of TE speech has the potential of quantifying the voice quality and
      assisting the speech language pathologist in facilitating rehabilitation.
      Motivated in part by the recent advances in telecommunication industry for speech
      quality estimation, this paper investigated the application of an auditory model
      in predicting the ratings of TE speech by normal hearing listeners. The Moore
      Glasberg auditory model was employed to extract perceptually relevant features
      from the acoustic waveform, and these features were later combined to estimate
      the subjective ratings of TE speech. This approach was validated with a database
      of subjective ratings of speech samples recorded from 35 TE speakers. Results
      showed moderate correlations between the objective metrics and the subjective
      ratings, and these correlations were significantly better than those obtained
      with traditional methods used in the telecommunication applications.

PMID- 20136225
TI  - Age-related differences in vocal responses to pitch feedback perturbations: a
      preliminary study.
AB  - The present study tested the effect of age on voice fundamental frequency (F(0))
      responses to pitch-shifted feedback. Pitch-shift stimuli (-100 cents, 200 ms
      duration) were presented to 30 native-English speakers: 10 children (7-12 yrs),
      10 younger adults (19-21 yrs), and 10 older adults (60-73 yrs). Significantly
      larger response magnitudes were found in the older group compared to the children
      and young adult groups, while the longest latencies were associated with the
      children group as compared to the two adult groups. These findings provide
      preliminary evidence of an age effect on the modulation of vocal responses to
      pitch-shifted feedback.

PMID- 20136226
TI  - Acoustic and laryngographic measures of the laryngeal reflexes of linguistic
      prominence and vocal effort in German.
AB  - This study uses acoustic and physiological measures to compare laryngeal reflexes
      of global changes in vocal effort to the effects of modulating such aspects of
      linguistic prominence as sentence accent, induced by focus variation, and word
      stress. Seven speakers were recorded by using a laryngograph. The laryngographic
      pulses were preprocessed to normalize time and amplitude. The laryngographic
      pulse shape was quantified using open and skewness quotients and also by applying
      a functional version of the principal component analysis. Acoustic measures
      included the acoustic open quotient and spectral balance in the vowel /e/ during
      the test syllable. The open quotient and the laryngographic pulse shape indicated
      a significantly shorter open phase for loud speech than for soft speech. Similar
      results were found for lexical stress, suggesting that lexical stress and loud
      speech are produced with a similar voice source mechanism. Stressed syllables
      were distinguished from unstressed syllables by their open phase and pulse shape,
      even in the absence of sentence accent. Evidence for laryngeal involvement in
      signaling focus, independent of fundamental frequency changes, was not as
      consistent across speakers. Acoustic results on various spectral balance measures
      were generally much less consistent compared to results from laryngographic data.

PMID- 20136227
TI  - Compensations in response to real-time formant perturbations of different
      magnitudes.
AB  - Previous auditory perturbation studies have demonstrated that talkers
      spontaneously compensate for real-time formant-shifts by altering formant
      production in a manner opposite to the perturbation. Here, two experiments were
      conducted to examine the effect of amplitude of perturbation on the compensatory
      behavior for the vowel /epsilon/. In the first experiment, 20 male talkers
      received three step-changes in acoustic feedback: F1 was increased by 50, 100,
      and 200 Hz, while F2 was simultaneously decreased by 75, 125, and 250 Hz. In the
      second experiment, 21 male talkers received acoustic feedback in which the shifts
      in F1 and F2 were incremented by +4 and -5 Hz on each utterance to a maximum of
      +350 and -450 Hz, respectively. In both experiments, talkers altered production
      of F1 and F2 in a manner opposite to that of the formant-shift perturbation.
      Compensation was approximately 25%-30% of the perturbation magnitude for shifts
      in F1 and F2 up to 200 and 250 Hz, respectively. As larger shifts were applied,
      compensation reached a plateau and then decreased. The similarity of results
      across experiments suggests that the compensatory response is dependent on the
      perturbation magnitude but not on the rate at which the perturbation is
      introduced.

PMID- 20136228
TI  - A mathematical model of vowel identification by users of cochlear implants.
AB  - A simple mathematical model is presented that predicts vowel identification by
      cochlear implant users based on these listeners' resolving power for the mean
      locations of first, second, and/or third formant energies along the implanted
      electrode array. This psychophysically based model provides hypotheses about the
      mechanism cochlear implant users employ to encode and process the input auditory
      signal to extract information relevant for identifying steady-state vowels. Using
      one free parameter, the model predicts most of the patterns of vowel confusions
      made by users of different cochlear implant devices and stimulation strategies,
      and who show widely different levels of speech perception (from near chance to
      near perfect). Furthermore, the model can predict results from the literature,
      such as Skinner, et al. [(1995). Ann. Otol. Rhinol. Laryngol. 104, 307-311]
      frequency mapping study, and the general trend in the vowel results of Zeng and
      Galvin's [(1999). Ear Hear. 20, 60-74] studies of output electrical dynamic range
      reduction. The implementation of the model presented here is specific to vowel
      identification by cochlear implant users, but the framework of the model is more
      general. Computational models such as the one presented here can be useful for
      advancing knowledge about speech perception in hearing impaired populations, and
      for providing a guide for clinical research and clinical practice.

PMID- 20136229
TI  - Unsupervised speech segmentation: an analysis of the hypothesized phone
      boundaries.
AB  - Despite using different algorithms, most unsupervised automatic phone
      segmentation methods achieve similar performance in terms of percentage correct
      boundary detection. Nevertheless, unsupervised segmentation algorithms are not
      able to perfectly reproduce manually obtained reference transcriptions. This
      paper investigates fundamental problems for unsupervised segmentation algorithms
      by comparing a phone segmentation obtained using only the acoustic information
      present in the signal with a reference segmentation created by human
      transcribers. The analyses of the output of an unsupervised speech segmentation
      method that uses acoustic change to hypothesize boundaries showed that acoustic
      change is a fairly good indicator of segment boundaries: over two-thirds of the
      hypothesized boundaries coincide with segment boundaries. Statistical analyses
      showed that the errors are related to segment duration, sequences of similar
      segments, and inherently dynamic phones. In order to improve unsupervised
      automatic speech segmentation, current one-stage bottom-up segmentation methods
      should be expanded into two-stage segmentation methods that are able to use a mix
      of bottom-up information extracted from the speech signal and automatically
      derived top-down information. In this way, unsupervised methods can be improved
      while remaining flexible and language-independent.

PMID- 20136230
TI  - Nonlinear progressive waves in a slide trombone resonator.
AB  - The propagation of finite-amplitude waves inside a slide trombone is studied
      through direct pressure measurements corresponding to dynamic extremes. A two
      microphone method is used to separate left-moving and right-moving waves inside
      the trombone, permitting the detection of nonlinear effects associated with
      progressive waves. It is found that a redistribution of energy across the
      spectrum toward the higher-frequencies occurs for large distances and high
      initial pressure levels. These results are consistent with the theory of weakly
      nonlinear acoustics and also with those reported in this same context by other
      authors, but which have been obtained mostly through examination of standing
      waves.

PMID- 20136231
TI  - Ultrasound characterization of red blood cell aggregation with intervening
      attenuating tissue-mimicking phantoms.
AB  - The analysis of the ultrasonic frequency-dependent backscatter coefficient of
      aggregating red blood cells reveals information about blood structural
      properties. The difficulty in applying this technique in vivo is due to the
      frequency-dependent attenuation caused by intervening tissue layers that distorts
      the spectral content of signals backscattered by blood. An optimization method is
      proposed to simultaneously estimate tissue attenuation and blood structure
      properties, and was termed the structure factor size and attenuation estimator
      (SFSAE). An ultrasound scanner equipped with a wide-band 25 MHz probe was used to
      insonify porcine blood sheared in both Couette and tubular flow devices. Since
      skin is one of the most attenuating tissue layers during in vivo scanning, four
      skin-mimicking phantoms with different attenuation coefficients were introduced
      between the transducer and the blood flow. The SFSAE gave estimates with relative
      errors below 25% for attenuations between 0.115 and 0.411 dBMHz and kR<2.08 (k
      being the wave number and R the aggregate radius). The SFSAE can be useful to
      examine in vivo and in situ abnormal blood conditions suspected to promote
      pathophysiological cardiovascular consequences.

PMID- 20136232
TI  - Black-capped (Poecile atricapillus) and mountain chickadee (Poecile gambeli)
      contact call contains species, sex, and individual identity features.
AB  - The tseet contact call, common to both black-capped and mountain chickadees, is
      among the most frequently produced call of each species, but has remained little
      studied until now. In the current study, the authors characterized the tseet call
      of adult allopatric and sympatric black-capped and mountain chickadees in terms
      of nine acoustic features in a fashion similar to descriptive accounts of both
      species' chick-a-dee calls. Summary statistics, the potential for individual
      coding, and classification by linear discriminant analysis were used to describe
      the tseet call. The authors were able to correctly classify tseet calls in terms
      of which group or individual produced it with high accuracy. Furthermore, several
      acoustic features are highly individualized, indicating that the chickadees may
      use these features to identify signalers as individuals or members of a
      particular group.

PMID- 20136233
TI  - Time-frequency and advanced frequency estimation techniques for the investigation
      of bat echolocation calls.
AB  - In this paper, techniques for time-frequency analysis and investigation of bat
      echolocation calls are studied. Particularly, enhanced resolution techniques are
      developed and/or used in this specific context for the first time. When compared
      to traditional time-frequency representation methods, the proposed techniques are
      more capable of showing previously unseen features in the structure of bat
      echolocation calls. It should be emphasized that although the study is focused on
      bat echolocation recordings, the results are more general and applicable to many
      other types of signal.

PMID- 20136234
TI  - The effect of signal duration on the underwater hearing thresholds of two harbor
      seals (Phoca vitulina) for single tonal signals between 0.2 and 40 kHz.
AB  - The underwater hearing sensitivities of two 2-year-old female harbor seals were
      quantified in a pool built for acoustic research by using a behavioral psycho
      acoustic technique. The animals were trained only to respond when they detected
      an acoustic signal ("go/no-go" response). Detection thresholds were obtained for
      pure tone signals (frequencies: 0.2-40 kHz; durations: 0.5-5000 ms, depending on
      the frequency; 59 frequency-duration combinations). Detection thresholds were
      quantified by varying the signal amplitude by the 1-up, 1-down staircase method,
      and were defined as the stimulus levels, resulting in a 50% detection rate. The
      hearing thresholds of the two seals were similar for all frequencies except for
      40 kHz, for which the thresholds differed by, on average, 3.7 dB. There was an
      inverse relationship between the time constant (tau), derived from an exponential
      model of temporal integration, and the frequency [log(tau)=2.86-0.94 log(f);tau
      in ms and f in kHz]. Similarly, the thresholds increased when the pulse was
      shorter than approximately 780 cycles (independent of the frequency). For pulses
      shorter than the integration time, the thresholds increased by 9-16 dB per decade
      reduction in the duration or number of cycles in the pulse. The results of this
      study suggest that most published hearing thresholds <or=1 kHz for harbor seals
      are probably not absolute, as they were derived from signals with durations
      shorter than the time constants for those frequencies.

PMID- 20136235
TI  - Quantitative test for sensory hand symptoms based on mechanoreceptor-specific
      vibrotactile thresholds.
AB  - A vibrotactile test for assessing the presence or absence of sensory symptoms in
      the hand has been developed from thresholds believed mediated by Merkel disks and
      Meissner corpuscles at the fingertips. It is constructed from the summed
      differences between the thresholds recorded at the fingertip of an individual and
      the mean values of the threshold for healthy persons at the same stimulation
      frequencies. The summed normalized threshold shift, TS(Sum(SD)), is shown to be
      related to reports by subjects of numbness and pain using three statistical tests
      for evaluating the significance of associations in 2x2 contingency tables. The
      small number of subjects (15) restricts direct calculation of a fence value for
      TS(Sum(SD)), t, between the presence and absence of symptoms: accordingly,
      interpolation between calculated t values has been performed graphically. A
      common range of t values can be identified that is judged significantly by each
      statistical test (3.3<or=t<3.9 for numbness; 3.6<or=t<4.1 for pain). The range
      encompasses the boundary previously identified between "normal" and "abnormal"
      vibrotactile thresholds, that is, thresholds for which the (two-sided)
      probability of occurrence in the hands of healthy persons is p approximately
      0.05.

PMID- 20136236
TI  - Encapsulated contrast microbubble radial oscillation associated with
      postexcitation pressure peaks.
AB  - This work combines modeling and experiment to assess encapsulated microbubble
      oscillations associated with broadband pressure peaks detected after microbubble
      excitation (postexcitation signals). Data were acquired from albumin-shelled and
      phospholipid-shelled microbubbles using a passive cavitation detector consisting
      of a confocally aligned 2.8-MHz transmitter and 13-MHz receiver. Microbubbles in
      weak solutions were insonified with a 5-cycle pulse at a peak rarefactional
      pressure of 2.0+/-0.2 MPa. For each microbubble type, at least 100 received
      signals were identified as individual-microbubble responses. The average
      broadband noise from signals with postexcitation response was 4.2-7.2 dB higher
      than from signals without postexcitation. Pressure-time responses for each
      microbubble type were simulated using the model by Marmottant et al. [J. Acoust.
      Soc. Am. 118, 3499-3505 (2005)], with insonification conditions matching the
      experiment. Increased broadband noise predicted for microbubbles with
      postexcitation response was consistent with that observed experimentally (4.0-8.9
      dB). The model predicted that postexcitation signals occur only when the radial
      oscillation exceeds both the shell break-up threshold and twice the initial
      radius (free bubble inertial cavitation threshold).

PMID- 20136298
TI  - Communications: Infrared spectroscopy of gas phase C3H3+ ions: the cyclopropenyl
      and propargyl cations.
AB  - C(3)H(3)(+) ions produced with a pulsed discharge source and cooled in a
      supersonic beam are studied with infrared laser photodissociation spectroscopy in
      the 800-4000 cm(-1) region using the rare gas tagging method. Vibrational bands
      in the C-H stretching and fingerprint regions confirm the presence of both the
      cyclopropenyl and propargyl cations. Because there is a high barrier separating
      these two structures, they are presumed to be produced by different routes in the
      plasma chemistry; their relative abundance can be adjusted by varying the ion
      source conditions. Prominent features for the cyclopropenyl species include the
      asymmetric carbon stretch (nu(5)) at 1293 cm(-1) and the asymmetric C-H stretch
      (nu(4)) at 3182 cm(-1), whereas propargyl has the CH(2) scissors (nu(4)) at 1445,
      the C-C triple bond stretch (nu(3)) at 2077 and three C-H stretches (nu(2),
      nu(9), and nu(1)) at 3004, 3093, and 3238 cm(-1). Density functional theory
      computations of vibrational spectra for the two isomeric ions with and without
      the argon tag reproduce the experimental features qualitatively; according to
      theory the tag atom only perturbs the spectra slightly. Although these data
      confirm the accepted structural pictures of the cyclopropenyl and propargyl
      cations, close agreement between theoretical predictions and the measured
      vibrational band positions and intensities cannot be obtained. Band intensities
      are influenced by the energy dependence and dynamics of photodissociation, but
      there appear to be fundamental problems in computed band positions independent of
      the level of theory employed. These new data provide infrared signatures in the
      fingerprint region for these prototypical carbocations that may aid in their
      astrophysical detection.

PMID- 20136299
TI  - Interpolation schemes for peptide rearrangements.
AB  - A variety of methods (in total seven) comprising different combinations of
      internal and Cartesian coordinates are tested for interpolation and alignment in
      connection attempts for polypeptide rearrangements. We consider Cartesian
      coordinates, the internal coordinates used in CHARMM, and natural internal
      coordinates, each of which has been interfaced to the OPTIM code and compared
      with the corresponding results for united-atom force fields. We show that
      aligning the methylene hydrogens to preserve the sign of a local dihedral angle,
      rather than minimizing a distance metric, provides significant improvements with
      respect to connection times and failures. We also demonstrate the superiority of
      natural coordinate methods in conjunction with internal alignment. Checking the
      potential energy of the interpolated structures can act as a criterion for the
      choice of the interpolation coordinate system, which reduces failures and
      connection times significantly.

PMID- 20136300
TI  - Relativistic quantum Monte Carlo method using zeroth-order regular approximation
      Hamiltonian.
AB  - We propose a new relativistic treatment in the quantum Monte Carlo (QMC)
      technique using the zeroth-order regular approximation (ZORA) Hamiltonian. The
      novel ZORA local energy is derived, and its availability is examined with some
      variational Monte Carlo calculations. We optimize the wave functions
      variationally and evaluate the relativistic and correlation effects
      simultaneously. It is shown that our ZORA-QMC method with Jastrow-Slater wave
      functions can recover not only relativistic effects but also almost the same
      amount of electron correlations as the nonrelativistic QMC method can by
      evaluating the ionization potentials of the first row atoms, Li-Ne.

PMID- 20136301
TI  - Variational geminal-augmented multireference self-consistent field theory: two
      electron systems.
AB  - We introduce a geminal-augmented multiconfigurational self-consistent field
      method for describing electron correlation effects. The approach is based on
      variational optimization of a MCSCF-type wave function augmented by a single
      geminal. This wave function is able to account for some dynamic correlation
      without explicit excitations to virtual molecular orbitals. Test calculations on
      two-electron systems demonstrate the ability of the proposed method to describe
      ionic and covalent electronic states in a balanced way, i.e., including the
      effects of both static and dynamic correlation simultaneously. Extension of the
      theory to larger systems will potentially provide an alternative to standard
      multireference methods.

PMID- 20136302
TI  - Short-time Fourier transform analysis of real-time time-dependent Hartree-Fock
      and time-dependent density functional theory calculations with Gaussian basis
      functions.
AB  - We propose a novel analysis of real-time (RT) time-dependent Hartree-Fock and
      time-dependent density functional theory (TDHF/TDDFT) calculations using a short
      time Fourier transform (STFT) technique. RT-TDHF/TDDFT calculations of model
      dimers were carried out and analyzed using the STFT technique, in addition to the
      usual Fourier transform (FT). STFT analysis revealed that the induced
      polarization propagated between the molecules through the intermolecular
      interaction; that is, it directly showed the electron dynamics of the excited
      system. The dependence of the propagation period on the intermolecular distance
      of the dimer was investigated. We also proved the possibility of describing, not
      just the valence, but also the core excitations by FT analysis of the RT
      TDHF/TDDFT calculations of a formaldehyde monomer with Gaussian basis functions
      compared with conventional TDHF/TDDFT results.

PMID- 20136303
TI  - Method and basis set dependence of anharmonic ground state nuclear wave functions
      and zero-point energies: application to SSSH.
AB  - One of the largest remaining errors in thermochemical calculations is the
      determination of the zero-point energy (ZPE). The fully coupled, anharmonic ZPE
      and ground state nuclear wave function of the SSSH radical are calculated using
      quantum diffusion Monte Carlo on interpolated potential energy surfaces (PESs)
      constructed using a variety of method and basis set combinations. The ZPE of
      SSSH, which is approximately 29 kJ mol(-1) at the CCSD(T)/6-31G* level of theory,
      has a 4 kJ mol(-1) dependence on the treatment of electron correlation. The
      anharmonic ZPEs are consistently 0.3 kJ mol(-1) lower in energy than the harmonic
      ZPEs calculated at the Hartree-Fock and MP2 levels of theory, and 0.7 kJ mol(-1)
      lower in energy at the CCSD(T)/6-31G* level of theory. Ideally, for sub-kJ mol(
      1) thermochemical accuracy, ZPEs should be calculated using correlated methods
      with as big a basis set as practicable. The ground state nuclear wave function of
      SSSH also has significant method and basis set dependence. The analysis of the
      nuclear wave function indicates that SSSH is localized to a single symmetry
      equivalent global minimum, despite having sufficient ZPE to be delocalized over
      both minima. As part of this work, modifications to the interpolated PES
      construction scheme of Collins and co-workers are presented.

PMID- 20136304
TI  - Circumstantial evidence in support of bivelocity hydrodynamic theory for
      mixtures.
AB  - Based upon findings with respect to the viability of the expression j(v)=
      rhoD(v)nablav hypothesized to represent the constitutive equation for the
      diffusive volume flux in ideal binary mixtures (rho=mass density,
      v=1/rho=specific volume, and D(v)=volume diffusion coefficient), implicit
      evidence is offered in support of the recently developed theory of bivelocity
      continuum hydrodynamics for mixtures. Present findings for the case of mixtures
      add to existing evidence already available for the single-component case, thus
      supporting the viability of bivelocity hydrodynamic theory in general.

PMID- 20136305
TI  - The "weighted ensemble" path sampling method is statistically exact for a broad
      class of stochastic processes and binning procedures.
AB  - The "weighted ensemble" method, introduced by Huber and Kim [Biophys. J. 70, 97
      (1996)], is one of a handful of rigorous approaches to path sampling of rare
      events. Expanding earlier discussions, we show that the technique is
      statistically exact for a wide class of Markovian and non-Markovian dynamics. The
      derivation is based on standard path-integral (path probability) ideas, but
      recasts the weighted-ensemble approach as simple "resampling" in path space.
      Similar reasoning indicates that arbitrary nonstatic binning procedures, which
      merely guide the resampling process, are also valid. Numerical examples confirm
      the claims, including the use of bins which can adaptively find the target state
      in a simple model.

PMID- 20136306
TI  - Correlation consistent basis sets for molecular core-valence effects with
      explicitly correlated wave functions: the atoms B-Ne and Al-Ar.
AB  - Correlation consistent basis sets have been optimized for accurately describing
      core-core and core-valence correlation effects with explicitly correlated F12
      methods. The new sets, denoted cc-pCVnZ-F12 (n=D, T, Q) and aug-cc-pC(F12)VnZ
      (n=D, T, Q, 5), were developed by augmenting the cc-pVnZ-F12 and aug-cc-pVnZ
      families of basis sets with additional functions whose exponents were optimized
      based on the difference between all-electron and valence-electron correlation
      energies. The number of augmented functions added is fewer, in general, than in
      the standard cc-pCVnZ and cc-pwCVnZ families of basis sets. Optimal values of the
      geminal Slater exponent for use with these basis sets in MP2-F12 calculations are
      presented and are also recommended for CCSD-F12b calculations. Auxiliary basis
      sets for use in the resolution of the identity approximation in explicitly
      correlated calculations have also been optimized and matched to the new cc-pCVnZ
      F12 series of orbital basis sets. The cc-pCVnZ-F12 basis sets, along with the new
      auxiliary sets, were benchmarked in CCSD(T)-F12b calculations of spectroscopic
      properties on a series of homo- and heteronuclear first and second row diatomic
      molecules. Comparing the effects of correlating the outer core electrons in these
      molecules with those from conventional CCSD(T) at the complete basis set limit,
      which involved calculations with new cc-pCV6Z basis sets for the second row
      elements that were also developed in the course of this work, it is observed that
      the F12 values are reasonably well converged already at just the triple-zeta
      level.

PMID- 20136307
TI  - Accelerating self-consistent field convergence with the augmented Roothaan-Hall
      energy function.
AB  - Based on Pulay's direct inversion iterative subspace (DIIS) approach, we present
      a method to accelerate self-consistent field (SCF) convergence. In this method,
      the quadratic augmented Roothaan-Hall (ARH) energy function, proposed recently by
      Host and co-workers [J. Chem. Phys. 129, 124106 (2008)], is used as the object of
      minimization for obtaining the linear coefficients of Fock matrices within DIIS.
      This differs from the traditional DIIS of Pulay, which uses an object function
      derived from the commutator of the density and Fock matrices. Our results show
      that the present algorithm, abbreviated ADIIS, is more robust and efficient than
      the energy-DIIS (EDIIS) approach. In particular, several examples demonstrate
      that the combination of ADIIS and DIIS ("ADIIS+DIIS") is highly reliable and
      efficient in accelerating SCF convergence.

PMID- 20136308
TI  - B3LYP calculations of cerium oxides.
AB  - In this paper we evaluate the performance of density functional theory with the
      B3LYP functional for calculations on ceria (CeO(2)) and cerium sesquioxide
      (Ce(2)O(3)). We demonstrate that B3LYP is able to describe CeO(2) and Ce(2)O(3)
      reasonably well. When compared to other functionals, B3LYP performs slightly
      better than the hybrid functional PBE0 for the electronic properties but slightly
      worse for the structural properties, although neither performs as well as
      LDA+U(U=6 eV) or PBE+U(U=5 eV). We also make an extensive comparison of atomic
      basis sets suitable for periodic calculations of these cerium oxides. Here we
      conclude that there is currently only one type of cerium basis set available in
      the literature that is able to give a reasonable description of the electronic
      structure of both CeO(2) and Ce(2)O(3). These basis sets are based on a 28
      electron effective core potential (ECP) and 30 electrons are attributed to the
      valence space of cerium. Basis sets based on 46 electron ECPs fail for these
      materials.

PMID- 20136309
TI  - Critical behavior of interacting monomers adsorbed on one-dimensional channels
      arranged in a triangular cross-sectional structure: mixed interactions along and
      across the channels.
AB  - Monte Carlo simulations and finite-size scaling analysis have been carried out to
      study the critical behavior in a submonolayer lattice-gas which mimics a
      nanoporous environment. In this model, the adsorbent is modeled as one
      dimensional channels of equivalent adsorption sites arranged in a triangular
      cross-sectional structure. Two kinds of lateral interaction energies have been
      considered: (1) w(L) interaction energy between nearest-neighbor particles
      adsorbed along a single channel and (2) w(T) interaction energy between particles
      adsorbed across nearest-neighbor channels. We focus on the case of repulsive
      transverse (w(T)>0) and attractive longitudinal (w(L)<0) lateral interactions,
      where a rich variety of structural orderings are observed in the adlayer
      depending on the value of the parameters k(B)T/w(T) (being k(B) the Boltzmann
      constant) and w(L)/w(T). The results reveal the existence of a first-order phase
      transition in the adlayer between a low-temperature "condensed" phase and a high
      temperature "disordered" phase.

PMID- 20136310
TI  - Hyperfine interaction and Stark effect in the b 3Pi-X 1Sigma+(0,0) band of copper
      monofluoride, CuF.
AB  - The low-rotational levels of the b (3)Pi-X (1)Sigma(+)(0,0) band of copper
      monofluoride, CuF, were recorded field free and in the presence of a static
      electric field. The field-free spectrum was analyzed to produce a refined set of
      fine and hyperfine parameters for the b (3)Pi(v=0) state. The permanent electric
      dipole moment, mu, for the b (3)Pi(v=0) and X (1) summation operator(+)(v=0)
      states were determined to be 2.36(2) and 5.26(2) D, respectively, from the
      analysis of the observed Stark shifts. The experimental mu values are compared to
      theoretical predictions. The change in mu upon excitation and the hyperfine
      parameters are discussed in terms of the proposed electronic configuration for
      the b (3)Pi and X (1)Sigma(+) states. The optical Stark spectroscopy of the A
      (2)Pi(3/2)-X (2)Sigma(+)(0,0) subband of YO was also recorded and analyzed to
      precisely calibrate the electric field strength. The determined mu values are
      3.714(5) and 4.542(40) D for the A (2)Pi(3/2)(v=0) and X (2)Sigma(+)(v=0) states,
      respectively.

PMID- 20136311
TI  - Theoretical study of the bonding in M(n+)-RG complexes and the transport of M(n+)
      through rare gas (M=Ca, Sr, and Ra; n=1 and 2; and RG=He-Rn).
AB  - We present high level ab initio potential energy curves for the M(n+)-RG
      complexes, where n=1 and 2; RG=He-Rn; and M=Ca, Sr, and Ra. Spectroscopic
      constants have been derived from these potentials and are compared with a wide
      range of experimental and previous theoretical data, and good agreement is
      generally seen. Large changes in binding energy, D(e), and bond length, R(e),
      between M(+)-He, M(+)-Ne, and M(+)-Ar, also found previously in the analogous
      Ba(+)-RG complexes [M. F. McGuirk et al., J. Chem. Phys. 130, 194305 (2009)], are
      identified and the cause investigated; the results shed light on the previous
      Ba(+)-RG results. These unusual trends are not observed for the dicationic
      complexes, which behave in a fashion similar to the isoelectronic alkali metal
      ion complexes. The potentials have also been employed to calculate transport
      coefficients for M(n+) moving through a bath of rare gas (RG) atoms.

PMID- 20136312
TI  - Excited states of PbF: a four-component relativistic study.
AB  - The electronic states of lead monofluoride (PbF) are studied from the (Pb 6s)(2)
      (F 2p-pi)(4) (F 2p-sigma)(2) (Pb 6p-pi)(1) X(1) ground state up to the F state,
      using the four-component relativistic configuration interaction and Fock-space
      coupled-cluster singles and doubles methods. Difficulties arising from the
      valence-Rydberg mixing are overcome by using a flexible basis set including
      Rydberg-type diffuse functions and by large-scale correlation calculations. The
      excited states are successfully characterized with the help of computed
      transition dipole moments. The three lowest-lying states (X(1), X(2), and A) are
      confirmed to be valence states arising from the (Pb 6p) spinors. The B state is
      assigned to the lowest Rydberg state (Omega=1/2), represented by a single
      excitation from the (Pb 6p-pi) spinor to the (F 3s) Rydberg spinor. Its
      calculated excitation energy (4.30 eV) is comparable to the observed one (4.42
      eV). The C state is a multiconfigurational valence state whose dominant
      configuration is represented by (Pb 6s)(2) (F 2p-pi)(4) (F 2p-sigma)(1) (Pb 6p
      pi)(2). Its calculated excitation energy (4.71 eV) is in good agreement with
      experiment (4.72 eV). The remaining D, E, and F states are assigned as Rydberg
      states. The calculated ionization potential (7.44 eV) is also close to the value
      (7.55 eV) determined recently by multiphoton ionization experiments.

PMID- 20136313
TI  - Reinvestigation of the Rb2 (2)3Pi(g)-a 3Sigma(u)+ band on helium nanodroplets.
AB  - It is well known that alkali-metal molecules are preferentially observed in the
      weak van der Waals-bound high spin states by helium droplet isolation
      spectroscopy. In [F. R. Bruhl et al., J. Chem. Phys. 115, 10275 (2001)] the Rb(2)
      (2)(3)Pi(g)-a (3)Sigma(u)(+) band on He droplets was investigated by laser
      induced fluorescence and dispersed emission spectroscopy. At that time no
      information on the magnitude of spin-orbit coupling was available for the
      (2)(3)Pi(g) state which connects to the atomic 5s+4d asymptote and it was
      neglected. In this work we reinvestigate the observed spectra. The dispersed
      emission spectra, which resulted from free molecules, are consistent with state
      of-the-art nonrelativistic potential energy surfaces and effective spin-orbit
      coupling matrix elements obtained from resonance-enhanced multiphoton ionization
      spectroscopy of cold Rb dimers [J. Lozeille et al., Eur. Phys. J. D 39, 261
      (2006)]. Having validated the theoretical description of the free molecule state,
      we use the laser-induced fluorescence spectrum to discuss the influence of the He
      droplet on the excitation band.

PMID- 20136314
TI  - Isomer identification and resolution in small gold clusters.
AB  - A variety of experimental techniques are used to resolve energetically close
      isomers of Au(7)(-) and Au(8)(-) by combining photoelectron spectroscopy and ab
      initio calculations. Two structurally distinct isomers are confirmed to exist in
      the cluster beam for both clusters. Populations of the different isomers in the
      cluster beam are tuned using Ar-tagging, O(2)-titration, and isoelectronic atom
      substitution by Cu and Ag. A new isomer structure is found for Au(7)(-), which
      consists of a triangular Au(6) unit with a dangling Au atom. Isomer-specific
      photoelectron spectra of Au(8)(-) are obtained from O(2)-titration experiment.
      The global minimum and low-lying structures of Au(7)(-), Au(8)(-), and MAu(n)(-)
      (n=6,7; M=Ag,Cu) are obtained through basin-hopping global minimum searches. The
      results demonstrate that the combination of well-designed photoelectron
      spectroscopy experiments (including Ar-tagging, O(2)-titration, and isoelectronic
      substitution) and ab initio calculation is not only powerful for obtaining the
      electronic and atomic structures of size-selected clusters, but also valuable in
      resolving structurally and energetically close isomers of nanoclusters.

PMID- 20136315
TI  - Indistinguishability and interference in the coherent control of atomic and
      molecular processes.
AB  - The subtle and fundamental issue of indistinguishability and interference between
      independent pathways to the same target state is examined in the context of
      coherent control of atomic and molecular processes, with emphasis placed on
      possible "which-way" information due to quantum entanglement established in the
      quantum dynamics. Because quantum interference between independent pathways to
      the same target state occurs only when the independent pathways are
      indistinguishable, it is first shown that creating useful coherence between
      nondegenerate states of a molecule for subsequent quantum interference
      manipulation cannot be achieved by collisions between atoms or molecules that are
      prepared in momentum and energy eigenstates. Coherence can, however, be
      transferred from light fields to atoms or molecules. Using a particular coherent
      control scenario, it is shown that this coherence transfer and the subsequent
      coherent phase control can be readily realized by the most classical states of
      light, i.e., coherent states of light. It is further demonstrated that quantum
      states of light may suppress the extent of phase-sensitive coherent control by
      leaking out some which-way information while "incoherent interference control"
      scenarios proposed in the literature have automatically ensured the
      indistinguishability of multiple excitation pathways. The possibility of quantum
      coherence in photodissociation product states is also understood in terms of the
      disentanglement between photodissociation fragments. Results offer deeper
      insights into quantum coherence generation in atomic and molecular processes.

PMID- 20136316
TI  - Anomalous nonlinear response of glassy liquids: general arguments and a mode
      coupling approach.
AB  - We study theoretically the nonlinear response properties of glass formers. We
      establish several general results, which together with the assumption of time
      temperature superposition, lead to a relation between the nonlinear response and
      the derivative of the linear response with respect to temperature. Using results
      from mode-coupling theory and scaling arguments valid close to the glass
      transition, we obtain the frequency and temperature dependence of the nonlinear
      response in the alpha- and beta-regimes. Our results demonstrate that supercooled
      liquids are characterized by responses to external perturbations that become
      increasingly nonlinear as the glass transition is approached. These results are
      extended to the case of inhomogeneous perturbing fields.

PMID- 20136317
TI  - Modeling the solid-liquid phase transition in saturated triglycerides.
AB  - We investigated theoretically two competing published scenarios for the melting
      transition of the triglyceride trilaurin (TL): those of (1) Corkery et al.
      [Langmuir 23, 7241 (2007)], in which the average state of each TL molecule in the
      liquid phase is a discotic "Y" conformer whose three chains are dynamically
      twisted, with an average angle of approximately 120 degrees between them, and
      those of (2) Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the
      liquid-state conformation of the TL molecule in the liquid phase is a nematic h*
      conformer whose three chains are in a modified "chair" conformation. We developed
      two competing models for the two scenarios, in which TL molecules are in a
      nematic compact-chair (or "h") conformation, with extended, possibly all-trans,
      chains at low-temperatures, and in either a Y conformation or an h* conformation
      in the liquid state at temperatures higher than the phase-transition temperature,
      T*=319 K. We defined an h-Y model as a realization of the proposal of Corkery et
      al. [Langmuir 23, 7241 (2007)], and explored its predictions by mapping it onto
      an Ising model in a temperature-dependent field, performing a mean-field
      approximation, and calculating the transition enthalpy DeltaH. We found that the
      most plausible realization of the h-Y model, as applied to the solid-liquid phase
      transition in TL, and likely to all saturated triglycerides, gave a value of
      DeltaH in reasonable agreement with the experiment. We then defined an
      alternative h-h* model as a realization of the proposal of Cebula et al. [J. Am.
      Oil Chem. Soc. 69, 130 (1992)], in which the liquid phase exhibits an average
      symmetry breaking similar to an h conformation, but with twisted chains, to see
      whether it could describe the TL phase transition. The h-h* model gave a value of
      DeltaH that was too small by a factor of approximately 3-4. We also predicted the
      temperature dependence of the 1132 cm(-1) Raman band for both models, and
      performed measurements of the ratios of three TL Raman bands in the temperature
      range of -20 degrees C < or = T < or = 90 degrees C. The experimental results
      were in accord with the predictions of the h-Y model and support the proposal of
      Corkery et al. [Langmuir 23, 7241 (2007)] that the liquid state is made up of
      molecules that are each, on average, in a Y conformation. Finally, we carried out
      computer simulations of minimal-model TLs in the liquid phase, and concluded that
      although the individual TL molecules are, on average, Y conformers, long-range
      discotic order is unlikely to exist.

PMID- 20136318
TI  - The longitudinal optic-like mode in molten alkali halides: a molecular dynamics
      approximation to inelastic x-ray scattering experiments.
AB  - The contribution of the long-wavelength fluctuations in the particle number,
      mass, and charge densities to the inelastic x-ray scattering dynamical structure
      factor for molten NaI and other molten alkali halides is accurately analyzed in
      the high frequencies region of the longitudinal optic-like mode. Molecular
      dynamics simulation results at low wave numbers are reported for the time
      correlations between the density components in the reciprocal space, namely, the
      corresponding intermediate scattering functions, and their spectra, namely, the
      dynamical structure factors. The time correlations between the longitudinal
      currents and their spectra are also reported. The importance of cross
      correlations is discussed. Moreover, the role played by the collective behavior
      of the two ionic species is also investigated. It is concluded that the
      longitudinal optic-like mode in molten alkali halides is unlikely to be detected
      by inelastic x-ray scattering experiments.

PMID- 20136319
TI  - Reactions of ruthenium and rhodium atoms with carbon monoxide and dinitrogen
      mixtures: a combined experimental and theoretical study.
AB  - Laser-ablated Ru and Rh atoms react with CO and N(2) mixture in excess neon to
      produce the carbonylmetal dinitrogen complexes, (NN)(n)MCO (M=Ru,Rh; n=1,2) and
      NNRu(CO)(2), as well as metal carbonyls and dinitrogen complexes. These
      carbonylmetal dinitrogen complexes are characterized using infrared spectroscopy
      on the basis of the results of the isotopic substitution and mixed isotopic
      splitting patterns. Density functional theory calculations have been performed on
      these complexes. Overall agreement between the experimental and calculated
      vibrational frequencies, relative absorption intensities, and isotopic shifts
      supports the identification of these species from the matrix infrared spectra.
      Furthermore, a plausible reaction pathway for the formation of the products has
      been proposed. This work reveals that the reactivity of Ru and Rh atoms toward CO
      is prior to N(2).

PMID- 20136320
TI  - Retardation effects breaking long-range orientational ordering in dipolar fluids.
AB  - A strongly coupled dipolar fluid confined in a sphere has been examined by Monte
      Carlo simulations using a modified distance-dependent pair interaction to emulate
      retardation effects. The effective dipole-dipole interaction and a property
      closely related to Kirkwood's g-factor have been analyzed for potentials with
      different distances at which the retardation effects became effective. The
      retardation effects were found to break the otherwise long-range structural
      ordering occurring in strongly coupled dipolar fluids.

PMID- 20136321
TI  - Carrier transport simulation in a model liquid crystalline system with the
      biaxial Gay-Berne potential.
AB  - In this paper, we performed carrier transport simulation to understand the
      unusual temperature dependence of the carrier mobility observed in nematic liquid
      crystals. For this purpose, we made a model liquid crystalline system consisting
      of biaxial Gay-Berne particles, and then we simulated hopping transport between
      these particles. The hopping rate was formulated suitably for the biaxial Gay
      Berne particles based on the investigation of the electronic overlaps between
      actual aromatic molecules. The carrier transport simulation was performed by
      master equation method on the model system prepared by N-P-T ensemble Monte Carlo
      simulation. We reproduced gradual mobility increase in the nematic phase as a
      result of the change in the short range molecular order.

PMID- 20136322
TI  - The single donator-single acceptor hydrogen bonding structure in water probed by
      Raman spectroscopy.
AB  - In this work, the Raman spectra of aqueous C(12)E(5) solutions are recorded and
      utilized to demonstrate the existence of single donator-single acceptor (DA)
      hydrogen bonding in water. From Raman OH stretching bands of aqueous C(12)E(5)
      solutions, the relative intensity of 3430 cm(-1) subband increases with C(12)E(5)
      concentrations. For confined water, the DA hydrogen bonding can be expected to be
      the important hydrogen bonding species. Therefore, the 3430 cm(-1) component can
      be ascribed to OH vibration engaged in DA hydrogen bonding. This is in agreement
      with our recent explanation on Raman OH stretching band of water. For water at
      ambient conditions, the double donor-double acceptor (DDAA) and DA should be the
      dominant hydrogen bonding species, the ratio of DDAA to DA can be approximately
      to be 0.75:1, and the mean hydrogen bonding can be determined to be 2.75.

PMID- 20136323
TI  - Radiation chemistry in ammonia-water ices.
AB  - We studied the effects of 100 keV proton irradiation on films of ammonia-water
      mixtures between 20 and 120 K. Irradiation destroys ammonia, leading to the
      formation and trapping of H(2), N(2), NO, and N(2)O, the formation of cavities
      containing radiolytic gases, and ejection of molecules by sputtering. Using
      infrared spectroscopy, we show that at all temperatures the destruction of
      ammonia is substantial, but at higher temperatures (120 K), it is nearly complete
      (approximately 97% destroyed) after a fluence of 10(16) ions/cm(2). Using mass
      spectroscopy and microbalance gravimetry, we measure the sputtering yield of our
      sample and the main components of the sputtered flux. We find that the sputtering
      yield depends on fluence. At low temperatures, the yield is very low initially
      and increases quadratically with fluence, while at 120 K the yield is constant
      and higher initially. The increase in the sputtering yield with fluence is
      explained by the formation and trapping of the ammonia decay products, N(2) and
      H(2), which are seen to be ejected from the ice at all temperatures.

PMID- 20136324
TI  - Proton disorder and the dielectric constant of type II clathrate hydrates.
AB  - Computational studies are presented examining the degree of proton disorder in
      argon and molecular hydrogen sII clathrate hydrates. Results are presented using
      a variety of model potentials for the dielectric constant, the proton order
      parameter, and the molecular volume for the clathrate systems. The dielectric
      constant for the clathrate systems is found to be lower than the dielectric
      constant of ice in all models. The ratio of the clathrate to ice dielectric
      constant correlates well with the ratio of the densities, which is not the case
      for comparisons to the liquid, so that differences in the dielectric constants
      between ice and the clathrates are most likely due to differences in densities.
      Although the computed dielectric constant is a strong function of the model
      potential used, the ratio of the dielectric constant of ice to that of the
      clathrates is insensitive to the model potential. For the nonpolar guest
      molecules used in the current study, the degree proton of disorder is found to
      depend weakly on the identity of the guest but the dielectric constant does not
      appear to be sensitive to pressure or the type of guest.

PMID- 20136325
TI  - Generic behavior of the hydrodynamic function of charged colloidal suspensions.
AB  - We discuss the generic behavior of the hydrodynamic function H(q) and diffusion
      function D(q) characterizing the short-time diffusion in suspensions of charge
      stabilized colloidal spheres, by covering the whole fluid regime. Special focus
      is given to the behavior of these functions at the freezing transition specified
      by the Hansen-Verlet freezing rule. Results are presented in dependence on
      scattering wavenumber q, effective particle charge, volume fraction, salt
      concentration, and particle size, by considering both the low-charge and high
      charge branch solutions of static structure factors. The existence of two charge
      branches leads to the prediction of a re-entrant melting-freezing-melting
      transition for increasing particle concentration at very low salinity. A
      universal limiting contour line is derived for the principal peak height value of
      H(q), independent of particle charge and diameter, and concentration and
      salinity, which separates the fluid from the fluid-solid coexistence region. This
      line is only weakly dependent on the value of the structure factor peak height
      entering the Hansen-Verlet rule. A dynamic freezing criterion is derived in terms
      of the short-time cage diffusion coefficient, a quantity easily measurable in a
      scattering experiment. The higher-dimensional parameter scans underlying this
      study make use of the fast and highly efficient deltagamma-scheme in conjunction
      with the analytic rescaled mean spherical approximation input for the static
      structure factor. Our results constitute a comprehensive database useful to
      researchers performing dynamic scattering experiments on charge-stabilized
      dispersions.

PMID- 20136326
TI  - Translational and rotational friction on a colloidal rod near a wall.
AB  - We present particulate simulation results for translational and rotational
      friction components of a shish-kebab model of a colloidal rod with aspect ratio
      (length over diameter) L/D=10 in the presence of a planar hard wall. Hydrodynamic
      interactions between rod and wall cause an overall enhancement of the friction
      tensor components. We find that the friction enhancements to reasonable
      approximation scale inversely linear with the closest distance d between the rod
      surface and the wall, for d in the range between D/8 and L. The dependence of the
      wall-induced friction on the angle theta between the long axis of the rod and the
      normal to the wall is studied and fitted with simple polynomials in cos theta.

PMID- 20136327
TI  - First-principles study of ultrathin (2 x 2) Gd nanowires encapsulated in carbon
      nanotubes.
AB  - Using density-functional calculations, we investigate the structural and magnetic
      properties of ultrathin Gd and Gd-carbide nanowires (NWs) encapsulated in narrow
      carbon nanotubes (CNTs). The equilibrium geometry of an encapsulated (2 x 2) Gd
      NW is markedly different from that of bulk Gd crystals. The charge-density
      analysis shows pronounced spin-dependent electron transfer in the encapsulated Gd
      NW in comparison with that of Gd-carbide NWs. We conclude that Gd-CNT
      hybridization is primarily responsible for both the structural difference and
      electron transfer in the encapsulated Gd-NW.

PMID- 20136328
TI  - Fluid epitaxialization effect on velocity dependence of dynamic contact angle in
      molecular scale.
AB  - Molecular dynamics simulations were used to investigate the effect of epitaxial
      ordering of the fluid molecules on the microscopic dynamic contact angle. The
      simulations were performed in a Couette-flow-like geometry where two immiscible
      fluids were confined between two parallel walls moving in opposite directions.
      The extent of ordering was varied by changing the number density of the wall
      particles. As the ordering becomes more evident, the change in the dynamic
      contact angle tends to be more sensitive to the increase in the relative velocity
      of the contact line to the wall. Stress components around the contact line is
      evaluated in order to examine the stress balance among the hydrodynamic stresses
      (viscous stress and pressure), the deviation of Young's stress from the static
      equilibrium condition, and the fluid-wall shear stress induced by the relative
      motion between them. It is shown that the magnitude of the shear stress on the
      fluid-wall surface is the primary contribution to the sensitivity of the dynamic
      contact angle and that the sensitivity is intensified by the fluid ordering near
      the wall surface.

PMID- 20136329
TI  - Spin filter effect of manganese phthalocyanine contacted with single-walled
      carbon nanotube electrodes.
AB  - We present a theoretical study of the spin transport through a manganese
      phthalocyanine (MnPc) molecule sandwiched between two semi-infinite armchair
      single-walled carbon nanotube (SWCNT) electrodes. Ab initio modeling is performed
      by combing the nonequilibrium Green's function formalism with spin density
      functional theory. Our calculations show that MnPc not only can act as a nearly
      perfect spin filter, but also has a large transmission around the Fermi level,
      which is dominated by the highest occupied molecule orbital (HOMO). The HOMO of
      MnPc is found to be a singly filled doubly degenerate molecular orbital, where
      the electrodes' Fermi level can easily pin. The spin filter effect of MnPc is
      very robust regardless of whether the open ends of the SWCNT electrodes are
      terminated by hydrogen, fluorine, or carbon dimers, demonstrating its promising
      applications in future molecular spintronics.

PMID- 20136330
TI  - Two-bath model for activated surface diffusion of interacting adsorbates.
AB  - The diffusion and low vibrational motions of adsorbates on surfaces can be well
      described by a purely stochastic model, the so-called interacting single
      adsorbate model, for low-moderate coverages (theta < or approximately equal to
      0.12). Within this model, the effects of thermal surface phonons and adsorbate
      adsorbate collisions are accounted for by two uncorrelated noise functions, which
      arise in a natural way from a two-bath model based on a generalization of the one
      bath Caldeira-Leggett Hamiltonian. As an illustration, the model is applied to
      the diffusion of Na atoms on a Cu(001) surface with different coverages.

PMID- 20136331
TI  - Methane dissociation and adsorption on Ni(111), Pt(111), Ni(100), Pt(100), and
      Pt(110)-(1 x 2): energetic study.
AB  - We use density functional theory to examine 24 transition states for methane
      dissociation on five different metal surfaces. In our calculations, the nonlocal
      exchange-correlation effects are treated within the generalized gradient
      approximation using the Perdew-Burke-Ernzerhof functional. In all cases, the
      minimum energy path for dissociation is over a top site. The barriers are large,
      0.66-1.12 eV, and relatively insensitive to the rotational orientation of the
      (nonreacting) methyl group and the azimuthal orientation of the reactive C-H
      bond. There is a strong preference on the Pt surfaces for the methyl fragment to
      bond on the top site, while on the Ni surfaces there is a preference for the
      hollow or bridge sites. Thus, during the dissociation on Pt, only the low mass H
      atom needs to significantly move or tunnel, while on Ni, both the dissociating H
      and the methyl fragment move away from the top site. For all 24 configurations
      there is a strong force at the transition state to pucker the metal atom over
      which the reaction occurs. The resulting magnitude of the variation in the
      barrier height with the motion of this atom varies a bit from surface-to-surface,
      but is of the order of 1 eV/A. We derive a model for the effective reaction
      barrier height that includes the effects of lattice motion and substrate
      temperature and compare with recent experiments and other theoretical studies.

PMID- 20136332
TI  - A mean field approach for computing solid-liquid surface tension for nanoscale
      interfaces.
AB  - The physical properties of a liquid in contact with a solid are largely
      determined by the solid-liquid surface tension. This is especially true for
      nanoscale systems with high surface area to volume ratios. While experimental
      techniques can only measure surface tension indirectly for nanoscale systems,
      computer simulations offer the possibility of a direct evaluation of solid-liquid
      surface tension although reliable methods are still under development. Here we
      show that using a mean field approach yields great physical insight into the
      calculation of surface tension and into the precise relationship between surface
      tension and excess solvation free energy per unit surface area for nanoscale
      interfaces. Previous simulation studies of nanoscale interfaces measure either
      excess solvation free energy or surface tension, but these two quantities are
      only equal for macroscopic interfaces. We model the solid as a continuum of
      uniform density in analogy to Hamaker's treatment of colloidal particles. As a
      result, the Hamiltonian of the system is imbued with parametric dependence on the
      size of the solid object through the integration limits for the solid-liquid
      interaction energy. Since the solid-liquid surface area is a function of the size
      of the solid, and the surface tension is the derivative of the system free energy
      with respect to this surface area, we obtain a simple expression for the surface
      tension of an interface of arbitrary shape. We illustrate our method by modeling
      a thin nanoribbon and a solid spherical nanoparticle. Although the calculation of
      solid-liquid surface tension is a demanding task, the method presented herein
      offers new insight into the problem, and may prove useful in opening new avenues
      of investigation.

PMID- 20136333
TI  - Simulation of pseudopolyrotaxane formation and orientational order between
      pseudopolyrotaxanes.
AB  - We have performed Brownian dynamics simulations in order to investigate the
      formation of a pseudopolyrotaxane (PPRX) with cyclodextrins (CDs) and a polymer
      chain and the development of orientational order between PPRXs. The coarse
      grained model is used to model the CDs and the polymer chain. In our simulations,
      we observe the formation of a rodlike PPRX with up to six rings for 40 monomer
      chains. After the formation of the PPRX, the processes of inclusion and
      dissociation repeat for the rings at the end of the chain. However, the PPRX has
      more than three rings and maintains the rodlike shape. With regard to the motion
      of rings in the PPRX, we observe two kinds of motions--oscillating motion and
      shifting motion. In the oscillating motion, the rings move around a particular
      position on the chain and display thermal fluctuation and collisions with
      neighboring rings. In the shifting motion, all rings shift to another location
      along the chain during the processes of inclusion and dissociation. In our
      simulations, we also observed that the orientational order between PPRXs develops
      at low temperatures.

PMID- 20136334
TI  - Electric potential and bending rigidity of a wormlike particle in electrolyte
      solution.
AB  - Using the linearized Poisson-Boltzmann equation (LPB) we derive an asymptotic
      expansion for the electrostatic potential of charged torus immersed in solution
      of an electrolyte in the limit of high salinity and large major radius of the
      torus. The small parameter of this expansion is the ratio of the Debye length to
      the minor radius of the torus. We derive asymptotic expressions for the
      electrostatic free energy and for the electrostatic persistence length of a
      polyion of a finite thickness. We propose a simple interpolation formula,
      xi(el)=l(B)(sigma(0)/e)(2)bkappa(D)[1+kappa(D)/(4b)], that gives the
      electrostatic persistence length in terms of the Debye length kappa(D), the
      linear charge density (sigma(0)/e), and the thickness of the polyion, 2b. This
      formula reproduces the exact results from the LPB theory in the limits of high
      and low salt concentrations. For the entire range of salinities, our formula is
      in excellent agreement with the numerical LPB results for wormlike particles of
      varying thickness. For particles of vanishing thickness, this formula reduces to
      the classical Odijk-Skolnick-Fixman expression.

PMID- 20136335
TI  - Overcharging and charge reversal in the electrical double layer around the point
      of zero charge.
AB  - The ionic adsorption around a weakly charged spherical colloid, immersed in size
      asymmetric 1:1 and 2:2 salts, is studied. We use the primitive model (PM) of an
      electrolyte to perform Monte Carlo simulations as well as theoretical
      calculations by means of the hypernetted chain/mean spherical approximation
      (HNC/MSA) and the unequal-radius modified Gouy-Chapman (URMGC) integral
      equations. Structural quantities such as the radial distribution functions, the
      integrated charge, and the mean electrostatic potential are reported. Our Monte
      Carlo "experiments" evidence that near the point of zero charge, the smallest
      ionic species is preferentially adsorbed onto the macroparticle, independently of
      the sign of the charge carried by this tiniest electrolytic component, giving
      rise to the appearance of the phenomena of charge reversal (CR) and overcharging
      (OC). Accordingly, colloidal CR, due to an excessive attachment of counterions,
      is observed when the macroion is slightly charged and the coions are larger than
      the counterions. In the opposite situation, i.e., if the counterions are larger
      than the coions, the central macroion acquires additional like-charge (coions)
      and hence becomes "overcharged," a feature theoretically predicted in the past
      [F. Jimenez-Angeles and M. Lozada-Cassou, J. Phys. Chem. B 108, 7286 (2004)]. In
      other words, here we present the first simulation data on OC in the PM electrical
      double layer, showing that close to the point of zero charge, this novel effect
      surges as a consequence of the ionic size asymmetry. We also find that the
      HNC/MSA theory captures well the CR and OC phenomena exhibited by the computer
      experiments, especially as the macroion's charge increases. On the contrary, even
      if URMGC also displays CR and OC, its predictions do not compare favorably with
      the Monte Carlo data, evidencing that the inclusion of hard-core correlations in
      Monte Carlo and HNC/MSA enhances and extends those effects. We explain our
      findings in terms of the energy-entropy balance. In the field of electrophoresis,
      it has been generally agreed that the charge of a colloid in motion is partially
      decreased by counterion adsorption. Depending on the location of the macroion's
      slipping surface, the OC results of this paper could imply an increase in the
      expected electrophoretic mobility. These observations aware about the
      interpretation of electrokinetic measurements using the standard Poisson
      Boltzmann approximation beyond its validity region.

PMID- 20136336
TI  - Publisher's note: "Accurate description of phase diagram of clathrate hydrates at
      the molecular level" [J. Chem. Phys. 131, 244510 (2009)].

PMID- 20136337
TI  - Publisher's note: "An interpretation of the anomalous 1Pi vibronic structure in
      the far-UV spectrum of CO" [J. Chem. Phys. 132, 024311 (2010)].

PMID- 20136338
TI  - Dr Valter Rukavina - amateur painter.
AB  - In this essay Dr Valter Rukavina (Rijeka 1896-1972), excellent specialist in
      infectious diseases and professor of the Rijeka University School of Medicine, is
      presented as successful amateur painter. He had been refining his talent through
      relentless practice since the school days, complementing it with skills and
      advice from established painters he associated with. He favoured figurative,
      realistic and somewhat romantic expression for his themes such as coastal
      landscapes, marinas, Quarnero sceneries, still life in tempera or oil, and
      drawings in ink or sepia. Despite partial colour blindness, he successfully used
      colour. He featured in a number of group exhibitions such as that of amateur
      painters of Rijeka in 1950, of painters physicians of Yugoslavia (Zagreb, 1956),
      in the Second International Exhibition of Contemporary Art (Florence, 1964),
      exhibition of the Rijeka branch of the Croatian Association of Visual Artists
      (Belgrade, 1966), and the 1969 exhibition in Opatija. His native city hosted two
      one-man exhibitions, the first retrospective in 1971, while he was still alive,
      and the second posthumous in 2007, with a good selection of his life's work.

PMID- 20136339
TI  - Manuscript containing a collection of medical recipes written in 1776 by a
      Catholic priest Petar Kastelan of Croatia.
AB  - Over the past centuries, manuscripts containing collections of folk recipes for
      the treatment of diseases were written mostly by Catholic priests in Croatia.
      They were used to prepare remedies and gave directions for their use. These
      writings provide valuable information for ethnographers and historians of
      pharmacy and medicine. They describe the types and frequency of diseases
      afflicting humans and domestic animals in the past, development of
      ethnopharmacology, folk medical terminology, names of medicinal herbs, and the
      interaction between folk and science medicine. This is why they need a
      multidisciplinary approach to be evaluated properly. This paper presents the 1776
      Medicine Book by a priest Petar Kastelan from southern Croatia (Dalmatia). It was
      found in a private archive and has not yet been published. The collection is
      written in the Croatian Cyrillic script, which was mostly used from the Middle
      Ages to the second half of the 19th century by Catholic priests when they wanted
      to write in Croatian. The collection contains 250 recipes for human medical
      practice and 10 recipes for veterinary medical practice. Thirty recipes contain
      household advice. Materia medica of the manuscript is mostly composed of drugs of
      plant origin. Remedies of animal and mineral origin are also included, but to a
      smaller extent. Valuable information is given about the folk names for diseases
      and medicinal plants as well as descriptions of the ways of preparing remedies.
      Prayers for healing, void of sorcery and magic, are also included.

PMID- 20136340
TI  - The contribution of Jewish health professionals to the development of health care
      in Bosnia and Herzegovina.
AB  - Jews first came to Bosnia and Herzegovina in the 16th century after having been
      exiled from Spain. They were successful in several trades in their new
      surroundings. Many Jewish families gave more than one doctor or pharmacist. Dr
      Goldberger and his son Dr Aleksandar Goldberger were skilled surgeons; Dr Isak
      Samokovlija's daughter Rikica was a paediatrician and a university professor; Dr
      Sigmund Kaunitz and his sons Oskar and Pavle, conducted the autopsy on the
      Archduke Franz Ferdinand, heir to the imperial throne, and his wife Sophie. Jews
      have traditionally regarded health culture as an important issue; their religion
      includes medical and other precepts for healthy living, from personal and
      household hygiene to ritual ablutions and bathing. They were the first to make
      medicinal preparations and to sell them in their shops, known as attar shops. The
      Museum of Sarajevo now treasures the inventory of one such centuries-old attar
      shop, belonging to the Papo family. Thanks to their medical skills, Jews even
      treated the Pashas of Bosnia and Herzegovina. Dr Nisim zak treated Sijavos Pasha,
      and Dr Isak Salom was Omer Pasha Latas's physician. Bosnia and Herzegovina owes a
      lot to the knowledge and dedication of health-care workers of the Jewish origin.
      Sarajevo, Mostar, Zenica, Foca, and Trebinje have named streets after these
      humanists, who founded many institutions, and started new disciplines to address
      the burning health issues in B&H, and a number of whom laid down their lives to
      defend B&H.

PMID- 20136341
TI  - [Health resorts in Styria, Charinthia and Istria once (1897) and today (2007).].
AB  - The aim of this study is to determine which health resorts existed in 1897 in
      Istria, Carinthia and Styria region, how many of them are still in use today and
      how the spas and their offer were represented in the past and how they are
      represented today. The study is based on the textbook Balneotherapie II
      (Bibliothek des Arztes 1900) by prof. dr. Julius Glax. The second source of our
      study is based on the currently available presentation of the health resorts from
      the internet. The textbook Balneotherapie was intended for the post graduate
      education of physicians and general practitioners, so they could advise the
      patient on further treatment in an appropriate health resort. In the chapter
      Balneographie the author represented 1200 health resorts all over the world. From
      the book we have chosen the following regions: Istria, Carinthia and Styria which
      used to be three parts of the Austro-Hungarian Empire. Today they are divided in
      to three neighboring states: Croatia (Istria), Slovenia (Istria, Carinthia,
      Styria) and Austria (Carinthia, Styria). Within these regions Glax presented 22
      health resorts, 19 of them are still working today. Barbarabad/Barbara bath
      (Carinthia, Austria) does not exist either as a resort or as a city. Rimske
      toplice (Romerbad/Roman baths) and Rimski vrelec (Romerquelle/ Roman springs) in
      Styria region do not function as health resorts any more. Nowadays we make a
      difference between spa and health resorts. Spa resorts offer numerous forms of
      recreation for better well being. Health resorts offer health services, as well
      as neglected, but various forms of alternative treatments and recreation. Each
      spa and health resort is represented in brochures and on the World Wide Web
      individually. Tradition is usually not mentioned, it is neglected but the
      exception is Opatija (Abbazia) which past is usually presented in the brochures.
      The museum of medical tourism was opened in November 2007 in Opatija where you
      can admire the development of Opatija from a small village to a mundane health
      resort.

PMID- 20136342
TI  - Sixty years of the Veterinary Institute of Rijeka (1947-2007).
AB  - In the 19th-century Croatia the development of veterinary legislation and human
      medicine was of outstanding importance for the development of veterinary
      medicine. Human medicine, already well-developed at that time, was responsible
      for the whole veterinary service. Veterinary and some other associations also
      contributed to the development of veterinary medicine (Croatian and Slavonian
      Economic Society, 1841; Croatian and Slavonian Veterinary Society, 1893; School
      of Economy and Forestry in KriZevci, 1860; Public School of Farriery, 1886).
      Veterinary literature in Croatian also encouraged veterinary profession to
      organise itself.

PMID- 20136343
TI  - Hinko Emili of Rijeka: a physician, a scientist and a photography enthusiast.
AB  - This review is dedicated to the life and work of a physician, scientist, and
      university professor Hinko Emili (Rijeka, 1900-1983). Particular attention has
      been given to the artistic part of his vast work. As an epidemiologist, he was
      particularly interested in water (its sources, exploitation, distribution,
      disease-causing bacteria, microorganisms, and chemical elements in it). The
      article brings a bibliography counting 84 published research articles. Just as
      interesting is Dr Emili's work in photography, which went beyond mere hobby and
      has a genuine artistic merit. Well many documents witness to either of his
      passions. Describing the sophisticated artistic atmosphere in the Rijeka of the
      1920s and 1930s, this article shows how much of it is owed to amateur and art
      photography. It concludes that both passions of professor Hinko Emili- medicine
      and art photography - share a common drive, that is, his strong sense of humanism
      and a subtle outlook on the world of his time.

PMID- 20136344
TI  - Professor Valter Rukavina (1896-1972): life between medicine and painting.
AB  - This article on the occasion of the 111th birthday of professor Valter Rukavina
      (Rijeka, 1896-1972) recalls this extraordinary personality who is remembered by
      local and national history as an excellent physician, infectionist, university
      professor, equally successful scientist and practitioner, scholar and a polyglot,
      art lover, and last but not least, an extraordinary self-taught painter... He
      graduated from secondary school in Susak and studied medicine in Innsbruck, Graz,
      Vienna and Prague, where he received diploma in general practice in 1921. He
      started his career in Zagreb, then moved to Vrbovsko, KriZevci, Osijek, and
      Zlatar as district physician. Meanwhile, at the Institute of Epidemiology he
      specialised in bacteriology, epidemiology, serology, hygiene, and medical
      chemistry. He successfully organised anti-typhus campaigns and mass vaccinations
      against scarlet fever and diphtheria, and established local healthcare stations.
      After a brief stay in Zagreb, in WW2 he was transferred to Bosnia, returned to
      Zagreb, and since 1946 until his death he had lived in his native Rijeka, where
      he started an infectious diseases department that later grew into the School of
      Medicine clinic. Being a practitioner and a scientist, he was interested in all
      aspects of infectious diseases and contiguous areas, and made a major
      contribution with his systematic research and successful implementation of
      preventive measures and complete eradication of the great brucellosis epidemic
      that broke out in Istria after WW2. In addition to the membership in a number of
      professional associations, professor Rukavina was also an active member of the
      Rijeka chapter of the Croatian Association of Visual Artists.

PMID- 20136345
TI  - Dr.Phil. et Med. Hermann Von Schrotter: Skizzen eines feldarztes aus Montenegro-
      observations of a military physician on his visit to Montenegro.
AB  - This essay gives a review of a book by an Austrian physician Hermann von
      Schrotter Skizzen Eines Feldartes aus Montenegro (Observations of a Military
      Physician from Montenegro), Berlin - Wien 1913 on the occasion of its translation
      to Montenegrin and reprint in Cetinje, Montenegro in 2007. The book takes us back
      to the time of the preparations and attack on Scutari, which took place in 1912
      and 1913. The Montenegrin army achieved their military goal, but with numerous
      casualties, whose exact number has never been determined. The author, Hermann von
      Schrotter, confirmed this in his observations in the book. When the Montenegrin
      Red Cross asked for help, the organizations of the following countries responded:
      Austria, Czechoslovakia, England, France, The Netherlands, Italy, Germany,
      Russia, Switzerland, and Sweden. Apart from them, physicians were sent by the
      Slavonic Voluntary Society from St. Petersburg, the Boards of the Red Cross from
      Dubrovnik and Split, the National Board from Zadar; seven physicians came from
      the Bay of Boka and three physicians with three nurses came from Bosnia. I wish
      to stress that in those times the Red Cross offered aid, as it does today, to all
      the people in need, regardless of their political beliefs. The relations between
      Montenegro and Austria were poor back then, yet the Mission of the Austrian Red
      Cross generously gave assistance and relief to the Montenegrin people!

PMID- 20136346
TI  - Reminiscence of Dr. Emanuel Luxardo (1848-1905) and the family of Miho Klaic
      (1829-1896).
AB  - This article is a reminiscence of four distinctive public figures who were
      related by family and who played key roles in the development of public health in
      Dalmatia in the second half of the 19th and the beginning of the 20th century. Dr
      Emanuel Luxardo (1848-1905) was a prominent physician and an able manager of the
      Dubrovnik and Zadar hospitals. In spite of his Italian origin, he championed the
      Croatian national reformation in Dalmatia. His father-in-law Miho Klaic (1829-
      1896), as one of the most prominent Dalmatian politicians and champions of the
      national reformation movement, greatly contributed to the building of new
      hospitals in Zadar (1882), Sibenik (1883), and Dubrovnik (1888). The older of his
      two sons, Petar (1862-1910) was a lawyer and very active in the Dalmatian
      parliament, while the younger son Ljubo (1871-?) was a successful surgeon in
      Zadar and Split.

PMID- 20136347
TI  - Improving health workforce recruitment and retention in rural and remote regions
      of Nigeria.
AB  - CONTEXT: As highlighted by the 2006 World Health Report, Nigeria is one of 36 sub
      Saharan African countries in the midst of a health workforce crisis. Inadequacy
      of optimal numbers of health workers with the appropriate skills-set is most
      pronounced in the rural and remote regions of Nigeria where 52% of the population
      live. Mortality and morbidity data from limited surveys of Nigeria indicate
      greater unmet health needs in rural and remote regions than in urban areas.
      Spartan living conditions, non-existent rural workforce policies and strategies,
      and an inadequate number of health staff with skills appropriate to the health
      priorities of rural areas are several of the many factors attributable to the
      steady decline in Nigeria's rural and remote health system. Based on 7 years'
      experience as a public health physician in rural and remote northern Nigeria, the
      author provides a perspective on factors hindering health workforce recruitment
      and retention, and proposes approaches to sustainably improving the current
      unsatisfactory health workforce situation in Africa's most populous nation.
      ISSUES: This article posits that out-migration of health workers is not a
      critical contributor to health workforce shortages in Nigeria's rural and remote
      areas. More important factors include contraction of government health spending
      as a percentage of GDP despite deteriorating health conditions, public health
      management systems that operate by default rather than by design, spartan living
      conditions outside urban areas, inadequate training of appropriate cadres of
      health staff, limited facilities and medications for effective delivery of
      clinical services, and burnout of overworked and underpaid rural-based
      clinicians. Most current health policy and strategy documents in Nigeria do not
      adequately account for the unique demographic features and health issues which
      vary according to remoteness from major cities. Addressing rural and remote
      health workforce shortages in Nigeria should begin with the development of a well
      researched national rural and remote health strategy. LESSONS LEARNED: Sub
      optimal leadership and management at all levels of the public health sector,
      poverty, low motivation, inadequacy of health facilities and medications for
      effective delivery of health care, inadequacy of funding to employ qualified
      health staff, and primitive living conditions constitute major disincentives for
      skilled health workers to work in the rural and remote regions of Nigeria, and
      for declining productivity among existing health workers. Practical interventions
      to encourage recruitment and retention, and to assure improvements in the quality
      and popularity of appropriately designed training programs for health
      professionals needed in rural and remote regions of Nigeria are discussed. A need
      is highlighted for adequate planning and resource allocation to enable a
      systematic overhaul of encumbrances currently impacting on Nigeria's rural and
      remote health system. Lessons that may be adapted from successful rural and
      remote health workforce training and recruitment strategies in Tanzania are
      discussed.

PMID- 20136348
TI  - Oxidative stress induced by atrazine in rat erythrocytes: mitigating effect of
      vitamin E.
AB  - The present study investigates the propensity of atrazine to induce oxidative
      stress and its possible attenuation by vitamin E in rat erythrocytes, which is a
      convenient model to understand the oxidative damage induced by various
      xenobiotics. Experimental animals were administered atrazine (300 mg/kg body
      weight, daily) and/or vitamin E (100 mg/kg body weight, daily) orally for a
      period of 7, 14, and 21 days. Results indicated that the reduced glutathione
      (GSH) content of the erythrocytes of atrazine treated rats was significantly
      decreased as compared to the control group. Co-administration of vitamin E along
      with atrazine restored the GSH content of erythrocytes nearly to control levels.
      The activities of antioxidant enzymes such as superoxide dismutase, catalase,
      glutathione peroxidase, and glutathione-s-transferase were found to be increased
      significantly in the erythrocytes accompanied by a decrease in the activity of
      the glucose-6-phosophate dehydrogenase, following atrazine exposure. On the other
      hand, when vitamin E was co-administered along with atrazine, activities of these
      enzymes were found to be restored significantly. In conclusion, results of the
      study demonstrated that atrazine induced oxidative stress in rat erythrocytes, in
      terms of increased activities of the various antioxidant enzymes, and decreased
      content of reduced glutathione. However, vitamin E administration ameliorated the
      effects of atrazine, suggesting that vitamin E is a potential antioxidant against
      atrazine-induced oxidative stress.

PMID- 20136349
TI  - pH-sensitive magnetic alginate-chitosan beads for albendazole delivery.
AB  - Novel magnetic alginate-chitosan beads were prepared for the controlled delivery
      of albendazole. The magnetic beads were characterized by Fourier transform
      infrared spectroscopy (FTIR), scanning electron microscope (SEM), and vibrating
      sample magnetometry (VSM). The swelling behavior and in vitro release of
      albendazole from the beads has been investigated. The magnetic hydrogel beads had
      showed unique pH-dependent swelling behaviors and a continuous release of the
      entrapped albendazole occurred. From the magnetometer measurements data, the
      magnetic alginate-chitosan beads also had superparamagnetic property as well as
      fast magnetic response. The magnetic beads may be used as a magnetic drug
      targeting system for albendazole in the gastrointestinal tract.

PMID- 20136350
TI  - Modulating effect of Withania somnifera on TCA cycle enzymes and electron
      transport chain in azoxymethane-induced colon cancer in mice.
AB  - The aim of the present investigation was to evaluate the efficacy of Withania
      somnifera on tricarboxylic acid (TCA) cycle enzymes and electron transport chain
      in azoxymethane-induced experimental colon cancer in mice. Azoxymethane at the
      dose of 15 mg/kg body weight was induced intraperitoneally once in a week for 28
      days. The progression in colon tumor development was correlated with the
      appearance of the histological biomarker and aberrant crypt foci (ACF).
      Azoxymethane-induced colon cancer animals were treated with 400 mg/kg body weight
      of W. somnifera once in a week orally for 28 days. After the experimental period,
      the animals were killed and analyzed for TCA cycle key enzymes, such as
      isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate
      dehydrogenase (MDH), and alpha-keto glutarate dehydrogenase (alpha-KGDH). The
      modulating effect of W. somnifera on TCA cycle key enzymes and electron transport
      chain complexes were investigated against colon cancer induced by azoxymethane in
      Swiss albino mice. Decreased activities of TCA cycle key enzymes such as ICDH,
      SDH, MDH, and alpha-KGDH in colon cancer bearing animals were observed. W.
      somnifera administration normalized these enzyme levels in azoxymethane-induced
      experimental mice. These results suggested that W. somnifera is the promising
      chemotherapeutic agent for the treatment of colon cancer.

PMID- 20136351
TI  - Novel insights in pharmacogenetics of drug response in Parkinson's disease.

PMID- 20136353
TI  - Pharmacogenetics of hepatitis C therapy.

PMID- 20136354
TI  - Pharmacogenomics: paving the path to personalized medicine.
AB  - The 2009 Golden Helix Symposium on Pharmacogenomics and Personalized medicine was
      held in Athens, Greece, where approximately 150 participants from 21 countries
      were updated on recent developments in the fields of pharmacogenetics and
      pharmacogenomics. The meeting was supported by ten corporate entities, of which
      three were major pharmaceutical and two were technology companies. It was
      endorsed by the University of Chicago and partly funded by the University of
      Patras. Here, we report some highlights of this meeting.

PMID- 20136355
TI  - Long-term genome-wide blood RNA expression profiles yield novel molecular
      response candidates for IFN-beta-1b treatment in relapsing remitting MS.
AB  - AIMS: In multiple sclerosis patients, treatment with recombinant IFN-beta (rIFN
      beta) is partially efficient in reducing clinical exacerbations. However, its
      molecular mechanism of action is still under scrutiny. MATERIALS & METHODS: We
      used DNA microarrays (Affymetrix, CA, USA) and peripheral mononuclear blood cells
      from 25 relapsing remitting multiple sclerosis patients to analyze the
      longitudinal transcriptional profile within 2 years of rIFN-beta administration.
      Sets of differentially expressed genes were attained by applying a combination of
      independent criteria, thereby providing efficient data curation and gene
      filtering that accounted for technical and biological noise. Gene ontology term
      association analysis and scientific literature text mining were used to explore
      evidence of gene interaction. RESULTS: Post-therapy initiation, we identified 42
      (day 2), 175 (month 1), 103 (month 12) and 108 (month 24) differentially
      expressed genes. Increased expression of established IFN-beta marker genes, as
      well as differential expression of circulating IFN-beta-responsive candidate
      genes, were observed. MS4A1 (CD20), a known target of B-cell depletion therapy,
      was significantly downregulated after one month. CMPK2, FCER1A, and FFAR2
      appeared as hitherto unrecognized multiple sclerosis treatment-related
      differentially expressed genes that were consistently modulated over time.
      Overall, 84 interactions between 54 genes were attained, of which two major gene
      networks were identified at an earlier stage of therapy: the first (n = 15 genes)
      consisted of mostly known IFN-beta-activated genes, whereas the second (n = 12)
      mainly contained downregulated genes that to date have not been associated with
      IFN-beta effects in multiple sclerosis array research. CONCLUSION: We achieved
      both a broadening of the knowledge of IFN-beta mechanism-of-action-related
      constituents and the identification of time-dependent interactions between IFN
      beta regulated genes.

PMID- 20136356
TI  - Functional polymorphisms and methotrexate treatment outcome in recent-onset
      rheumatoid arthritis.
AB  - AIMS: Clinical response to methotrexate (MTX) treatment differs among rheumatoid
      arthritis patients. Genetic variation can partly account for this phenomenon. In
      this study, functional polymorphisms in genes related to the mechanism of action
      of MTX or immunopathogenesis of rheumatoid arthritis were studied for association
      with treatment outcome in a Dutch cohort of patients with early rheumatoid
      arthritis. Furthermore, tests for replication of previous research on these
      genetic variants were performed according to reported end points. MATERIALS &
      METHODS: Seven polymorphisms in seven genes were analyzed in 205 genotyped
      patients with active rheumatoid arthritis. All patients received standardized MTX
      treatment (< or =25 mg per week orally) combined with folic acid. MTX treatment
      outcome was evaluated by disease activity score criteria and adverse drug events.
      The following genetic variants were analyzed and correlated: ABCB1 3435C>T, ITPA
      IVS2 +21A>C, HLA-G (-14 bp >+14 bp), TGFB1 +869T>C and TLR4 +896A>G. In case of
      significant differences, regression analyses were applied. Since carriers of the
      minor alleles of the SNPs DHFR 829C>T and IMPDH2 +787C>T were not observed, no
      statistical analyses could be performed. RESULTS: No significant associations or
      replications of these genetic variants with MTX efficacy were demonstrated.
      Regarding toxicity, patients carrying the ABCB1 3435T-allele and TLR4 +896G
      allele were 2.5-times more likely to develop adverse drug events at 6 months
      (odds ratio: 2.6; 95% CI: 1.1-6.2, and odds ratio: 2.5; 95% CI: 1.1-6.1,
      respectively). Additionally, this chance increased almost fourfold in patients
      with the two unfavorable genotypes (odds ratio: 3.9; 95% CI: 1.5-10.3). However,
      none of these associations remained significant after correction for multiple
      testing (p < 0.004). CONCLUSION: Our data indicate that MTX toxicity was
      potentially associated with ABCB1 3435C>T and TLR4 +896A>G. However, after
      correction, none of these associations remained significant. Furthermore, no
      significant associations or replications of these functional variants with
      efficacy were found.

PMID- 20136357
TI  - Are patients with intermediate TPMT activity at increased risk of
      myelosuppression when taking thiopurine medications?
AB  - Thiopurine S-methyltransferase (TPMT) metabolizes thiopurine medications,
      including azathioprine and 6-mercaptopurine. Absent TPMT activity (i.e., in
      individuals homozygous for a variant TPMT allele) is associated with an increased
      risk of myelosuppression in patients taking thiopurine drugs. However, it is not
      clear if there is also an increased risk for patients with intermediate TPMT
      activity (i.e., in individuals heterozygous for a variant TPMT allele). AIMS: To
      quantify the increased risk of myelosuppression for patients with intermediate
      TPMT activity. MATERIALS & METHODS: A systematic review identified published
      studies, up to 29 September 2008, that explored the relationship between TMPT and
      hematological adverse drug reactions to thiopurines. Following a critical
      appraisal of the quality of published studies, a meta-analysis calculated the
      odds ratio of myelosuppression for patients with intermediate TPMT activity
      compared with wild-type. RESULTS: A total of 67 studies were identified, the
      majority retrospective cohort in design. Patients with two TPMT variant alleles
      who are TPMT deficient have a substantial increase in their risk of myelotoxicity
      (86% of deficient patients developed myelosuppression). The increase in odds
      ratio of developing leukopenia for patients with intermediate TPMT activity or
      one TPMT variant allele compared with wild-type was 4.19 (95% CI: 3.20-5.48).
      CONCLUSION: This meta-analysis suggests that individuals with both intermediate
      and absent TPMT activity have an increased risk of developing thiopurine-induced
      myelosuppression, compared with individuals with normal activity. However, there
      is significant variability in the quality of the reported studies and large
      prospective studies to clarify the size of the effect of TPMT variant alleles on
      the risk of myelosuppression should be conducted. Accurate risk assessments will
      provide important data to inform clinical guidelines.

PMID- 20136358
TI  - New CYP2A6 gene deletion and conversion variants in a population of Black African
      descent.
AB  - AIMS: Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing
      nicotine and nitrosamine precarcinogens. Our aim was to discover and characterize
      new CYP2A6 alleles in a population of Black African descent. MATERIALS & METHODS:
      We used cloning, sequencing and genotyping of genomic DNA to discover new
      variants, and in vivo nicotine pharmacokinetic phenotyping to characterize the
      functional effect of the new alleles. RESULTS: Four new CYP2A6 alleles,
      CYP2A6*4G, *4H, *1B4 and *1L, were discovered and characterized in a population
      of Black African descent. The two new deletion alleles, CYP2A6*4G and *4H, are
      distinguished by different crossover junctions at 7.9 and 7.8 kb downstream of
      the CYP2A6 +1ATG start site, respectively; their combined allele frequency is
      1.6%. The new gene conversion alleles, CYP2A6*1B4 and CYP2A6*1L, contain 27 and
      10 bp of CYP2A7 sequence in the CYP2A6 3 -flanking region, respectively; their
      combined allele frequency is 7.3%. CYP2A6*4 appears to associate with lower
      CYP2A6 activity in vivo, while CYP2A6*1L does not; however, CYP2A6*1L confounds
      genotyping assays that use the 2A6R3 and 2A6R4 primers. CONCLUSION: As new
      variants are discovered, the relationships between CYP2A6 genotype, nicotine
      metabolism, smoking behaviors and tobacco-related cancer risk will be further
      clarified.

PMID- 20136359
TI  - Assessing the size of gene or RNAi effects in multifactor high-throughput
      experiments.
AB  - AIMS: To expand the recently proposed contrast variable and associated concepts
      to assess the size of gene effects or siRNA effects in multifactor high
      throughput experiments, as well as to serve the need to consider both mean and
      standardized mean of contrast (SMC). METHODS & RESULTS: The recently proposed
      concepts of contrast variable and SMC are expanded in the context of multifactor
      analysis of variance. Based on this expansion, SMC is explored as a tool for
      analyzing multifactor high-throughput data, a novel plot termed a dual-flashlight
      plot is proposed, and the incompatibility of false-discovery rates across
      experiments is demonstrated. The applications show that the results reached using
      expanded SMC and the dual-flashlight plot are more reasonable than those reached
      using p-value-based or false-discovery rate-based volcano plot for assessing
      differential expression, genetic dominance and linear/quadratic time-course
      changes. CONCLUSION: Compared with traditional contrast analysis, the expanded
      contrast variable and SMC may serve as an alternative that can address the real
      need of assessing the size of gene or siRNA effects in multifactor high
      throughput experiments.

PMID- 20136360
TI  - Classical twin design in modern pharmacogenomics studies.
AB  - Response to medication is highly variable, unpredictable and, at times, may be
      fatal. All drugs are more effective in certain groups of the population while
      showing no or minimal benefit in other groups. Although the current data on the
      subject are piecemeal, anecdotal evidence suggests that, in line with other
      common multifactorial traits, a myriad of genomic as well as environmental
      factors underpin population variability in drug response. Pharmacogenomics is the
      study of how variations in the human genome affect the variability in response to
      medication. Efforts to personalize treatment based on results from
      pharmacogenomics studies have the potential to increase efficacy, lower the
      overall cost of treatment, and decrease the incidence of adverse drug reactions,
      and are one of the major challenges of the modern era. The classical twin design
      has traditionally been used to assess the relative contribution of genetic and
      environmental factors to population variation in common, complex phenotypes,
      including drug response. Twins are not commonly regarded as providing the optimal
      design in genomic studies. However, we argue that, through their precise
      'matching' for confounding variables (age, sex, cohort and common environmental
      effects), their amenability to numerous nonclassical study designs (genome-wide
      association studies or the role of epigenetic factors), and the availability of
      large, established registries worldwide, the twin model represents a flexible
      study design for systems-biology studies of drug response in humans. In this
      review, we describe the 'classical twin model' and its application in traditional
      pharmacogenetics studies, discuss the value of the twin design in the modern
      systems biology era, and highlight the potential of existing twin registries in
      formulating future strategies in pharmacogenomics research. We argue that the
      usefulness of this design goes beyond its traditional applications. Moreover, the
      flexibility of the model in concert with the amenability of large, established
      registries of twins worldwide to the collecting of new phenotypes will mean that
      the study of identical and nonidentical twins will play a considerable role in
      shaping our understanding of the important factors that underpin population
      variability in common, complex phenotypes, including response to medication.

PMID- 20136361
TI  - Update on the clinical pharmacogenomics of organ transplantation.
AB  - Organ transplantation suffers from a static graft and patient survival rate, and
      a high incidence of serious adverse drug effects. The pharmacogenomics of organ
      transplantation has emerged only recently and is complementary to the
      immunogenetic information that has accumulated over the past decade. Gene
      polymorphism studies have focused on the genes that interact across the group of
      immunosuppressants, including ciclosporin, tacrolimus, sirolimus and
      corticosteroids. The polymorphisms that hold the most potential for use in a drug
      selection algorithm are in genes CYP3A5, ABCB1, IMPDH1 and IMPDH2, and cytokines
      and growth factors. Gene-expression arrays have led to gene-expression testing,
      such as the use of AlloMap((R)) with heart transplant patients. The expanded use
      of gene-expression assays, proteomics and drug selection algorithms in organ
      transplantation will progress slowly and may be outpaced by drug test co
      development programs for new transplant drugs. In the future, clinical
      pharmacogenomics will be a routine part of patient care for organ transplant
      patients.

PMID- 20136362
TI  - Pharmacogenetics of chronic obstructive pulmonary disease: challenges and
      opportunities.
AB  - Similar to other common chronic diseases, chronic obstructive pulmonary disease
      (COPD) is a heterogeneous disorder with multiple disease subtypes. Candidate gene
      studies have found genetic associations for COPD-related phenotypes that may be
      relevant for pharmacogenetics studies, including lung function decline and COPD
      exacerbations. However, few COPD pharmacogenetics studies have been completed.
      Most studies have focused on the role of variants in the beta(2)-adrenergic
      receptor gene on bronchodilator response, but the findings have been
      inconclusive. Candidate gene studies highlight the concept that genes for COPD
      susceptibility may also be relevant in COPD pharmacogenetics. Currently, there
      are no clinical applications of pharmacogenetics to COPD therapy, but the use of
      pharmacogenetics to determine initial smoking cessation therapy may be closer to
      clinical application.

PMID- 20136364
TI  - Errors and reproducibility of DNA array-based detection of allelic variants in
      ADME genes: PHARMAchip.
AB  - AIMS: Differences in adverse drug reactions can be explained by genetic
      variations, especially if they determine the expression of certain protein
      effectors and/or drug-metabolizing enzymes. Over the last decade, several tests
      screening for the most frequent polymorphisms in drug-metabolizing enzymes have
      been marketed for research and diagnostic purposes. The aim of this study was to
      assess the suitability of PHARMAchip for the genotyping of polymorphisms of genes
      associated with drug metabolism and response as an alternative to Jurilab Ltd's
      DrugMEt Test. MATERIALS & METHODS: In this observational study, performed using
      100 previously genotyped DNA samples, we report on common genes included in the
      two different tests examined: the former DrugMEt test and the recently introduced
      PHARMAchip test. RESULTS & CONCLUSION: Although these tests are based on
      different methodological approaches, we have found a high concordance of results
      between both methods. Some of the discrepancies between tests were related to
      allelic variants not monitored in a particular microarray and the quality of the
      genomic DNA used.

PMID- 20136363
TI  - Impact of the 1000 genomes project on the next wave of pharmacogenomic discovery.
AB  - The 1000 Genomes Project aims to provide detailed genetic variation data on over
      1000 genomes from worldwide populations using the next-generation sequencing
      technologies. Some of the samples utilized for the 1000 Genomes Project are the
      International HapMap samples that are composed of lymphoblastoid cell lines
      derived from individuals of different world populations. These same samples have
      been used in pharmacogenomic discovery and validation. For example, a cell-based,
      genome-wide approach using the HapMap samples has been used to identify
      pharmacogenomic loci associated with chemotherapeutic-induced cytotoxicity with
      the goal to identify genetic markers for clinical evaluation. Although the
      coverage of the current HapMap data is generally high, the detailed map of human
      genetic variation promised by the 1000 Genomes Project will allow a more in-depth
      analysis of the contribution of genetic variation to drug response. Future
      studies utilizing this new resource may greatly enhance our understanding of the
      genetic basis of drug response and other complex traits (e.g., gene expression),
      therefore, help advance personalized medicine.

PMID- 20136368
TI  - The proceedings of the diabetes in pregnancy study group of North America 2009
      conference.
AB  - The DPSG of North America (DPSG-NA) was inaugurated in 1997, and its initial
      meeting was commenced in San Antonio, Texas, in 1998. Since then, the DPSG-NA has
      held annual meetings, which are hosted by the home institution of members of the
      organizing committee on a rotating basis. This yeas, the DPSG-NA held its 11
      annual meeting in Baltimore, Maryland, and focused on the major controversies
      regarding the detection, diagnosis, and management of gestational diabetes
      mellitus (GDM). It included the latest information on the maternal and fetal
      consequences of GDM as well as summaries from the HAPO study, the Australian
      Carbohydrate Intolerance Study (ACHOIS) in pregnant women, and the National
      Institute of Child Health and Human Development Maternal Fetal Medicine (NICHD
      MFMU Network) study. In addition, extensive data were presented on the
      effectiveness of oral antihyperglycemic agents in managing GDM as well as data
      from studies examining their transfer across the placenta and effects on the
      fetus. Strategies for managing hypertensive disorders associated with GDM were
      also presented. Based on this year's presentations, the DPSG-NA coordinating
      committee has made recommendations on the screening and management of GDM and
      priorities for future research.

PMID- 20136369
TI  - Postural tachycardia syndrome complicating pregnancy.
AB  - OBJECTIVE: To review clinical experience at our institution on postural
      tachycardia syndrome (POTS) complicating pregnancy. METHODS: In a retrospective
      review, we identified nine pregnancies in seven patients with POTS syndrome at
      our institution. RESULTS: Patients who did not require treatment for POTS before
      conception were less likely to have an exacerbation of symptoms or need
      reintroduction of treatment. Exacerbations of POTS during pregnancy are variable.
      Of our patients with exacerbations of symptoms, increases in the existing
      pharmacologic treatments, such as increasing beta-blocker dosage, was effective
      in palliation of symptoms. There were seven vaginal deliveries. Two patients
      delivered without neuraxial anesthesia; the other five deliveries were done using
      epidural anesthesia without associated complications. POTS does not seem to
      contribute to pregnancy-related complications. Importantly, there were no adverse
      intrapartum events attributable to POTS. CONCLUSIONS: Pregnant women with POTS
      may undergo safe regional anesthesia and vaginal delivery. This contradicts
      earlier reports in the literature recommending cesarean delivery.

PMID- 20136370
TI  - Summary statement of the DPSG-NA organizing committee.

PMID- 20136371
TI  - Validation of a fluid-structure interaction model of solute transport in pores of
      cyclically deformed tissue scaffolds.
AB  - Convection induced by repetitive compression of porous tissue scaffolds enhances
      solute transport inside the scaffold. Our previous experiments have shown that
      pore size, shape, and orientation with respect to strain direction greatly
      influence loading-induced solute transport. The objective of this study was to
      develop a computational model of deformation-induced solute transport in porous
      tissue scaffolds, which included the pore geometry of the scaffold. This geometry
      consisted of a cubic scaffold with single channel in the middle of the scaffold,
      immersed in a fluid reservoir. Cylindrical pores with circular or elliptic cross
      section, and spheroid pores were modeled. The scaffold was cyclically compressed
      from one side, causing fluid motion and dispersion of solute inside the scaffold
      pore. Scaffold deformation was solved using the finite element method, and fluid
      flow and solute transport were solved using the finite volume method. The
      distortion of the scaffold-fluid interface was transferred as a boundary
      condition to the fluid flow solver. Both convection and diffusion were included
      in the computations. The solute transport rates in the different scaffold pore
      geometries agreed well with our previous experimental results obtained with X-ray
      microimaging. This model will be used to explore transport properties of a
      spectrum of novel scaffold designs.

PMID- 20136372
TI  - Endoscope-assisted radical perineal prostatectomy.
AB  - Dissection of the bladder neck is particularly important in patients who have
      previously had prostate surgery due to hyperplasia. We describe an endoscope
      assisted radical perineal prostatectomy (RPP) technique that facilitates the
      dissection of the prostate-vesical junction. The technique was employed in four
      patients with a history of transurethral prostate resection. Before dissecting
      the prostate from the bladder neck during RPP, we circumscribed the bladder neck
      perurethrally with a Collins knife. The remaining of the RPP procedure was
      performed via the traditional approach. The incision of the prostate-vesical
      junction with the Collins knife protected the bladder-neck integrity and made the
      dissection of this junction easier. The final pathologic diagnosis was organ
      confined prostate cancer with negative surgical margins. All the patients had
      continence during a 6-month follow-up. The major advantage of this technique is
      to precisely locate the prostate-vesical junction under direct vision. Our
      modified technique may prove to be a simple, less invasive, and oncologically
      safe method to manage the bladder neck perurethrally.

PMID- 20136373
TI  - Optimizing treatment of schizophrenia to minimize relapse.

PMID- 20136374
TI  - When should women be screened for postnatal depression?

PMID- 20136375
TI  - Levetiracetam: a comprehensive review.
AB  - Levetiracetam was approved by the US FDA in 1999 after failing the traditional
      screening tests for antiepileptic drugs. In the 10 years since its introduction,
      it has become one of the first-line antiepileptic agents and has been evaluated
      in small uncontrolled studies and case series as an off-label treatment for
      status epilepticus, for nonepileptic neurological conditions, such as movement
      disorders, neuropathic pain and headaches, and for some psychiatric conditions.
      It has not been approved for any indication other than chronic epilepsy. A
      significant factor in using levetiracetam for seizures and other disorders has
      been its ease of dosing and tolerability. In this article, we outline how
      levetiracetam was discovered, the animal and human data showing its antiepileptic
      activity, its potential use in other neurological conditions and the significant
      adverse events. We also discuss the direction antiepileptic drug development will
      take in the future.

PMID- 20136376
TI  - Clinical application of blood biomarkers in cerebrovascular disease.
AB  - Identifying a biomarker or panel of biomarkers of cerebral ischemia would have a
      major impact on the care of stroke patients by facilitating early management
      decisions and individualization of care. Biochemical surrogates of cerebral
      ischemia might also play an important role by identifying relevant pathways for
      novel therapeutic strategies and by facilitating early clinical trials in
      cerebrovascular disease. Serum biomarkers related to pathways of hemostasis,
      oxidation and inflammation, or alterations in glial and neuronal proteins, have
      been identified but none have been recommended for routine clinical use. This
      review describes the most promising biomarkers of cerebrovascular disease and the
      context and limitations in which they have been studied.

PMID- 20136377
TI  - Management of stroke in pregnancy and the puerperium.
AB  - Pregnancy and the puerperium have been recognized to increase the risk of stroke,
      particularly from late pregnancy and through the puerperium. The reported
      incidences of stroke during pregnancy and the puerperium varied widely, ranging
      from 5 to 67 per 100,000 deliveries or pregnancies. Important causes of stroke
      during pregnancy and the puerperium include preeclampsia and eclampsia,
      cardioembolism, rupture of cerebral vascular anomaly, peripartum or postpartum
      cerebral angiopathy and cerebral venous thrombosis. Management of patients with
      pregnancy-related stroke is largely the same as that of nonpregnant patients,
      with more consideration on maternal and fetal risks. Low-dose aspirin reduces the
      occurrence of perinatal deaths and preeclampsia in women with historical risk
      factors for preeclampsia. Anticoagulation during pregnancy is indicated for
      current arterial or venous thromboembolism, prior venous thromboembolism on long
      term anticoagulation, antiphospholipid syndrome with prior venous thromboembolism
      and patients with a mechanical heart valve. Data from thrombolytic therapy for
      pregnant women with acute ischemic stroke are limited. It is critical that the
      risks and benefits of thrombolytic therapy for pregnant women and fetuses are
      considered cautiously.

PMID- 20136378
TI  - Cerebral hemodynamic changes following carotid endarterectomy: 'cerebral
      hyperperfusion syndrome'.
AB  - Carotid endarterectomy is associated with significant changes in cerebral
      hemodynamics. In the chronically ischemic brain of patients with carotid
      stenosis, this can result in postoperative development of 'cerebral
      hyperperfusion syndrome'. This can cause severe cerebral edema, intracerebral
      hemorrhage and death. Impaired autoregulation as a result of endothelial
      dysfunction mediated by the generation of free oxygen radicals is implicated in
      the pathogenesis of cerebral hyperperfusion syndrome. Intensive blood pressure
      monitoring and control forms the backbone of treatment. Complete recovery occurs
      in mild cases, but disability and death can occur in more severe cases. This
      review concentrates on the mechanism, current management and identification of
      risk factors that can predispose to this rare but potentially life threatening
      complication.

PMID- 20136379
TI  - Blood pressure lowering and stroke.
AB  - Hypertension is the most prevalent of the modifiable risk factors for stroke. The
      benefits of blood pressure (BP) lowering on primary and secondary prevention of
      stroke are undeniable. Despite this, BP control in hypertensive individuals and
      patients with prior cerebrovascular events is suboptimal. Noncompliance,
      inappropriate antihypertensive usage and under-utilization of medications
      contribute significantly to inadequate BP control. Recently, elegantly designed
      studies that assessed the preventive role of BP lowering in patients with
      cerebrovascular disease have helped clarify management issues in terms of BP
      targets and effective antihypertensive regimens. Current evidence suggests that
      BP targets for primary and secondary prevention are suboptimal and need
      reassessment. The effect of BP modulation in acute stroke is still not completely
      understood. Although the thresholds for BP treatment in acute stroke have been
      recommended, BP targets are as yet ill-defined. The available evidence supports
      early lowering of blood pressure following stroke. This review discusses the
      impact of blood pressure on stroke incidence and outcomes, outlines the
      recommendations for blood pressure lowering in stroke and delineates questions
      that still need to be addressed.

PMID- 20136380
TI  - What is it with the weather and stroke?
AB  - An influence of climate upon cerebrovascular risk is both biologically plausible
      and supported by epidemiological evidence. These relationships are important as
      they could yield public health strategies to help protect the vulnerable from the
      increased death rates arising during extreme cold and heat waves. Change in
      temperature impacts on many cerebrovascular risk factors, including serum lipid
      and fibrinogen concentration and blood pressure. The relationship between stroke
      and meteorological variables is complex because of the number of potentially
      relevant meteorological variables, differences in study design and climate
      between geographical areas and potential for confounding. Behavioral factors are
      also influenced by the weather, which may in turn affect stroke risk. Some
      studies suggest that lower temperature increases stroke risk and others suggest
      the converse, while changes in atmospheric pressure may link with increased
      intracranial hemorrhage risk. To date, data are confusing and conflicting and
      well-conducted prospective studies are required to help clarify these potentially
      important relationships.

PMID- 20136381
TI  - Treatment of hoarding.
AB  - In the past 5 years, hoarding has emerged as a serious, potentially debilitating
      and remarkably frequent form of psychopathology. Attempts to treat it have met
      with little success. Although the majority of studies using serotonin-reuptake
      inhibitors have shown a poor response among people with hoarding disorder,
      serious methodological problems limit the conclusions that can be drawn from
      these studies. The true efficacy of serotonin-reuptake inhibitors for hoarding is
      largely unknown. Cognitive-behavioral treatments for obsessive-compulsive
      disorder have also fared badly in the treatment of hoarding. However, therapy
      based on a cognitive-behavioral model of hoarding has shown considerable promise.

PMID- 20136382
TI  - Hypnosis in the treatment of anxiety- and stress-related disorders.
AB  - Self-hypnosis training represents a rapid, cost-effective, nonaddictive and safe
      alternative to medication for the treatment of anxiety-related conditions. Here
      we provide a review of the experimental literature on the use of self-hypnosis in
      the treatment of anxiety and stress-related disorders, including anxiety
      associated with cancer, surgery, burns and medical/dental procedures. An overview
      of research is also provided with regard to self-hypnotic treatment of anxiety
      related disorders, such as tension headaches, migraines and irritable bowel
      syndrome. The tremendous volume of research provides compelling evidence that
      hypnosis is an efficacious treatment for state anxiety (e.g., prior to tests,
      surgery and medical procedures) and anxiety-related disorders, such as headaches
      and irritable bowel syndrome. Although six studies demonstrate changes in trait
      anxiety, this review recommends that further randomized controlled outcome
      studies are needed on the hypnotic treatment of generalized anxiety disorder and
      in documenting changes in trait anxiety. Recommendations are made for selecting
      clinical referral sources.

PMID- 20136383
TI  - Role of dopamine in the pathophysiology and treatment of obsessive-compulsive
      disorder.
AB  - The differential effects of serotonin-reuptake inhibitors on obsessive-compulsive
      disorder (OCD) were sufficient to presume that a serotonin regulatory disorder is
      the most essential part of the pathophysiology of OCD. In patients with OCD,
      however, a high-dose of serotonin-reuptake inhibitor monotherapy may not be
      sufficient, and approximately half of patients were noted to be treatment
      resistant. As results from previous studies have shown, there have been positive
      treatment responses to the dopaminergic antagonists. This suggests that other
      neurotransmitter systems, such as dopamine, are involved in the pathophysiology
      of OCD. Preclinical, neuroimaging and neurochemical studies have provided
      evidence demonstrating that the dopaminergic system is involved in inducing or
      aggravating the symptoms that are indicative of OCD. In this article, we review
      the dopaminergic system in OCD pathophysiology as well as reviewing the effect of
      drugs that act on dopaminergic activity in OCD.

PMID- 20136384
TI  - Current findings of fMRI in panic disorder: contributions for the fear
      neurocircuitry and CBT effects.
AB  - Thanks to brain imaging great advances have been made concerning the
      comprehension of neural substrates related to panic disorder (PD). This article
      aims to: review the recent functional MRI (fMRI) studies concerning PD; correlate
      the PD fMRI neurobiological findings with the fear neurocircuitry hypothesis;
      discuss the fear neurocircuitry hypothesis and link it to cognitive-behavior
      therapy findings; and comment on fMRI study limitations and suggest
      methodological changes for future research. As a whole, there is increasing
      evidence that brain structures such as the prefrontal cortex, the anterior
      cingulate cortex and limbic areas (hippocampus and amygdala) might play a major
      role in the panic response.

PMID- 20136385
TI  - Melatonin agonists and insomnia.
AB  - The ability of melatonin to shift biological rhythms is well known. As a result,
      melatonin has been used in the treatment of various circadian rhythm sleep
      disorders, such as advanced and delayed sleep phase disorders, jet lag and
      shiftwork disorder. The current evidence for melatonin being efficacious in the
      treatment of primary insomnia is less compelling. The development of agents that
      are selective for melatonin receptors provides opportunity to further elucidate
      the actions of melatonin and its receptors and to develop novel treatments for
      specific types of sleep disorders. The agonists reviewed here - ramelteon,
      tasimelteon and agomelatine - all appear to be efficacious in the treatment of
      circadian rhythm sleep disorders and some types of insomnia. However, further
      studies are required to understand the mechanisms of action, particularly for
      insomnia. Clinical application of the agonists requires a good understanding of
      their phase-dependent properties. Long-term effects of melatonin should be
      evaluated in large-scale, independent randomized controlled trials.

PMID- 20136386
TI  - Proton-beam therapy for tumors of the CNS.
AB  - The focus of this review is proton radiotherapy for primary neoplasms of the
      brain. Although glial cells are among the most radioresistant in the body, the
      presence of sensitive critical structures and the high doses needed to control
      CNS tumors present a formidable challenge to the treating radiation oncologist.
      Treatment with conventional photon radiation at doses required to control disease
      progression all too often results in unacceptable toxicity. Protons have
      intrinsic properties that often allow radiation oncologists to deliver a higher
      dose to the tumor compared with photons, while at the same time offering better
      sparing of normal tissues. Recognition of these advantages has resulted in
      development of many new proton treatment facilities worldwide.

PMID- 20136387
TI  - The effects of selective and nonselective phosphodiesterase inhibitors on
      phagocytic cells in mice.
AB  - Milrinone (1 mg/kg i.m.), sildenafil (1 mg/kg p.o), and aminophylline (20 mg/kg
      i.m.) were administered to mice once or five times. The drugs increased the
      production of IL-1beta and NO by peritoneal macrophages. Milrinone or
      aminophylline did not change the percentage of phagocytosing cells. A single
      administration of sildenafil increased the percentage of phagocytosing
      granulocytes (after 12 h). Sildenafil administered five times decreased the
      percentage of phagocytosing monocytes (72 h after the last dose). A single
      administration of the drugs did not change the oxidative burst activity. PDE
      inhibitors administered five times temporarily enhanced the percentage of cells
      producing reactive oxidants.

PMID- 20136388
TI  - Tumor control after surgery and radiotherapy for pineocytoma.
AB  - OBJECT: Pineocytoma is a rare tumor, and the current literature on these tumors
      is primarily composed of case reports and small case series. Thus,
      recommendations on appropriate treatment of these tumors are highly varied.
      Therefore, the authors performed a systematic review of the literature on tumor
      control after surgery for pineocytoma to determine the relative benefits of
      aggressive resection and postoperative adjuvant radiotherapy. METHODS: A
      comprehensive search of the published English-language literature was performed
      to identify studies citing outcome data of patients undergoing surgery for
      pineocytoma. Determination of rates of progression-free survival (PFS) was
      performed using Kaplan-Meier analysis. RESULTS: Sixty-four articles met the
      criteria of the established search protocol, which combined for a total of 166
      patients. Twenty-one percent of these patients had undergone a biopsy procedure,
      38% had undergone subtotal resection (STR), 42% had undergone gross-total
      resection, and 28% were treated with radiation therapy. The 1- and 5-year PFS
      rates for the resection group versus the biopsy group were 97 and 90% (1 year),
      and 89 and 75% (5 years), respectively (p < 0.05, log-rank test). The 1- and 5
      year PFS rates for the GTR group versus the group undergoing STR combined with
      radiation therapy were 100 and 94% (1 year), and 100 and 84% (5 years),
      respectively (p < 0.05, log-rank test). There was no significant difference in
      PFS for STR only compared with STR in addition to radiation therapy. CONCLUSIONS:
      Gross-total resection is the ideal treatment for pineocytoma and might represent
      a cure for these lesions. When gross-total resection is not possible, adjuvant
      radiation therapy after STR is of questionable benefit for these patients.

PMID- 20136389
TI  - Image-guided frameless stereotactic biopsy without intraoperative
      neuropathological examination.
AB  - OBJECT: Stereotactic biopsy is a safe and effective technique for the diagnosis
      of brain tumors. The use of intraoperative neuropathological examination has been
      routinely advocated to increase diagnostic yield, but the procedure lengthens
      surgical time, may produce false-negative and -positive results, and current
      biopsy techniques have a very low nondiagnostic rate. Therefore, the authors
      questioned the need for intraoperative histological evaluation. METHODS: The
      authors prospectively studied all patients undergoing image-guided biopsy under
      the care of a single surgeon (P.L.G.) between July 2005 and October 2007. A
      Stryker neuronavigation system with a trajectory guide was used to plan a single
      trajectory, and, using a side-cutting biopsy cannula, multiple biopsy samples
      were taken from between 1 and 4 sites within the tumor. Tissue was inspected
      macroscopically by the surgeon and was only submitted for neuropathological
      assessment postoperatively. RESULTS: One hundred thirty-four biopsies were
      performed during the study. A positive diagnosis was established in 133 cases
      (99.3%). One biopsy was negative (0.7%) and postoperative imaging (performed
      because the tissue was macroscopically normal) demonstrated inaccurate targeting
      of the lesion. Significant complications were seen in 3 patients (2.2%) who all
      had preoperative WHO performance scores of III or IV. Two patients suffered
      delayed deterioration and died due to probable surgical complications--one with
      thalamic glioblastoma multiforme (GBM) and one with gliomatosis cerebri. One
      patient with GBM suffered an intracerebral hematoma that was managed
      conservatively. Postoperative seizures were seen in 4 patients (3%), and 2
      patients (1.5%) experienced a transient neurological deficit. Histological
      diagnosis showed a GBM in 64 cases, Grade III glioma in 19, Grade I or II in 23,
      metastasis in 10, lymphoma in 13, and other disease in 4. There were 32 patients
      discharged to home on the same day as surgery. Compared with the authors'
      previous retrospective audit into 127 biopsies, this technique showed improved
      diagnostic yield (99.3 vs 94.5%, p = 0.032) with fewer complications (2.2 vs 4.7%
      [not statistically significant]). CONCLUSIONS: This technique of image-guided
      biopsy has high diagnostic yield with acceptably low morbidity and may be
      performed as a day case. Intraoperative neuropathological examination would not
      have increased the diagnostic yield further in this study, and its routine use
      may not be necessary. In the authors' department pounds sterling 70,350
      (UK)/$114,522 (US) would have been saved by not using intraoperative
      neuropathology in this series. Therefore, intraoperative neuropathology should no
      longer be routinely recommended.

PMID- 20136390
TI  - Long-range plasticity between intact hemispheres after contralateral cervical
      nerve transfer in humans.
AB  - OBJECT: Peripheral nerve injury in a limb usually causes intrahemispheric
      functional reorganization of the contralateral motor cortex. Recently, evidence
      has been emerging for significant interhemispheric cortical plasticity in humans,
      mostly from studies of direct cortical damage. However, in this study, a long
      range interhemispheric plasticity was demonstrated in adults with brachial plexus
      avulsion injury (BPAI) who had received a contralateral cervical nerve transfer,
      and this plasticity reversed the BPAI-induced intrahemispheric cortical
      reorganization. METHODS: In this study, 8 adult male patients with BPAI were
      studied using PET scanning. RESULTS: The results indicated that the right
      somatomotor cortices, which may contribute to the control of the injured limb
      before brachial plexus deafferentation, still played an important role when
      patients with BPAI tried to move their affected limbs, despite the fact that the
      contralateral C-7 nerve transfer had been performed and the peripheral output had
      changed dramatically. Such findings are consistent with the results of the
      authors' previous animal study. CONCLUSIONS: The brain may try to restore the
      control of an injured limb to its original cortex area, and a complicated change
      of peripheral pathway also can induce long-range interhemispheric cortical
      reorganization in human motor cortex.

PMID- 20136391
TI  - Alteration of thrombospondin-1 and -2 in rat brains following experimental
      intracerebral hemorrhage. Laboratory investigation.
AB  - OBJECT: Spontaneous intracerebral hemorrhage (ICH) is among the most intractable
      forms of stroke. Angiogenesis, an orchestrated balance between proangiogenic and
      antiangiogenic factors, is a fundamental process to brain development and repair
      by new blood vessel formation from preexisting ones and can be induced by ICH.
      Thrombospondin (TSP)-1 and TSP-2 are naturally occurring antiangiogenic factors.
      The aim of this study was to observe their expression in rat brains with ICH.
      METHODS: Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats
      by stereotactic injection of collagenase VII or autologous blood into the right
      globus pallidus. The expression of TSP-1 and -2 was evaluated by
      immunohistochemistry and quantitative real-time reverse transcription-polymerase
      chain reaction analysis. RESULTS: After the induction of ICH, some TSP1- or TSP2
      immunoreactive microvessels resided around the hematoma for ~ 7 days and extended
      into a clot thereafter. Cerebral endothelial cells expressed the TSPs. The
      expression of TSP-1 and TSP-2 mRNA peaked at 4 and 14 days after collagenase
      induced ICH, respectively. CONCLUSIONS: Findings in this study suggest that ICH
      can alter the expression of TSP-1 and TSP-2, which may be involved in modulating
      angiogenesis in brains following ICH.

PMID- 20136392
TI  - Onyx embolization of a carotid cavernous fistula via direct transorbital
      puncture.
AB  - The treatment of indirect carotid cavernous fistulas (CCFs) is challenging and
      primarily accomplished by endovascular means utilizing a variety of embolic
      agents. Transvenous access to the cavernous sinus is the preferred method of
      embolizaiton of indirect CCFs as they are frequently associated with numerous
      small-caliber meningeal branches. Although the inferior petrosal sinus is the
      simplest, shortest, and most commonly used venous route to the cavernous sinus,
      the superior ophthalmic vein, superior petrosal sinus, basilar plexus, and
      pterygoid plexus present other endovenous options. Occasionally, however, use of
      these venous routes may not be possible due to vessel tortuosity or sinus
      thrombosis and occlusion. The authors report a case of an indirect CCF that could
      not be treated endovascularly due to inability to access the cavernous sinus via
      a transfemoral transvenous approach. Angiography revealed a small, deeply located
      superior ophthalmic vein that was thought to be suboptimal for a direct cutdown.
      The cavernous sinus was cannulated directly via a transorbital approach using
      fluoroscopic guidance with a 3D skull reconstruction overlay. The fistula was
      subsequently obliterated using ethylene vinyl alcohol copolymer (Onyx). The
      technique and advantages of both 3D osseous reconstruction as well as Onyx
      embolization are discussed.

PMID- 20136393
TI  - Microvascular decompression after failed Gamma Knife surgery for trigeminal
      neuralgia: a safe and effective rescue therapy?
AB  - OBJECT: Stereotactic radiosurgical rhizolysis using Gamma Knife surgery (GKS) is
      an increasingly popular treatment for medically refractory trigeminal neuralgia.
      Because of the increasing use of GKS for trigeminal neuralgia, clinicians are
      faced with the problem of choosing a subsequent treatment plan if GKS fails. This
      study was conducted to identify whether microvascular decompression (MVD) is a
      safe and effective treatment for patients who experience trigeminal neuralgia
      symptoms after GKS. METHODS: From their records, the authors identified 29
      consecutive patients who, over a 2-year period, underwent MVD following failed
      GKS. During MVD, data regarding thickened arachnoid, adhesions between vessels
      and the trigeminal nerve, and trigeminal nerve atrophy/discoloration were noted.
      Outcome and complication data were also recorded. RESULTS: The MVD procedure was
      completed in 28 patients (97%). Trigeminal nerve atrophy was noted in 14 patients
      (48%). A thickened arachnoid was noted in 1 patient (3%). Adhesions between
      vessels and the trigeminal nerve were noted in 6 patients (21%) and prevented MVD
      in 1 patient. At last follow-up, 15 patients (54%) reported an excellent outcome
      after MVD, 1 (4%) reported a good outcome, 2 (7%) reported a fair outcome, and 10
      patients (36%) reported a poor outcome. After MVD, new or worsened facial
      numbness occurred in 6 patients (21%). Additionally, 3 patients (11%) developed
      new or worsened troubling dysesthesias. CONCLUSIONS: Thickened arachnoid,
      adhesions between vessels and the trigeminal nerve, and trigeminal nerve
      atrophy/discoloration due to GKS did not prevent completion of MVD. An MVD is an
      appropriate and safe "rescue" therapy following GKS, although the risks of
      numbness and troubling dysesthesias appear to be higher than with MVD alone.

PMID- 20136394
TI  - Flow patterns and velocity distributions in the human vertebrobasilar arterial
      system. Laboratory investigation.
AB  - OBJECT: The authors conducted a study to elucidate the relationship between the
      flow patterns and the formation of aneurysms at the bifurcation of the basilar
      artery (BA). METHODS: Six isolated, transparent vertebrobasilar arterial systems
      were prepared from humans postmortem, and flow patterns and velocity
      distributions were studied in detail using flow visualization and
      cinemicrographic techniques. RESULTS: The authors found that if the diameters of
      2 vertebral arteries (VAs) were nearly equal and they formed a symmetrical
      inverted Y-shaped junction with the BA, the BA flow was also symmetrical. The
      fluid elements that flowed into the BA from 2 VAs traveled almost parallel to the
      vessel wall of the BA without mixing with each other, and then they flowed out
      through ipsilateral superior cerebellar and posterior cerebral arteries. In
      contrast to this, if the diameters of 2 VAs were very different or the BA was
      badly bent, the BA flow was disturbed as a result of the formation of swirling
      and secondary flows. The approaching velocity profile at the BA's terminal
      bifurcation was flattened if the inverted Y-junction was symmetrical, and it was
      sharpened if the junction was asymmetrical. Thus, in the latter case, fluid
      elements impinged on the vessel wall around the flow divider of the bifurcation
      with much larger velocities and, hence, larger kinetic energy, compared with the
      case of a symmetrical inverted Y-junction, exerting high fluid pressures, wall
      shear stresses, and wall tensions on the vessel wall there. CONCLUSIONS: The
      symmetrical structure of the inverted Y-junction in a normal vertebrobasilar
      arterial system provides a flattened approaching velocity profile at the terminal
      bifurcation of the BA, lowering the hemodynamic stresses (pressure, tension, and
      shear stress) exerted on the wall of the bifurcation. This may account for the
      relatively low incidence of aneurysm formation at this site.

PMID- 20136395
TI  - Biopsies and neuropathology.

PMID- 20136396
TI  - Bacterial infections in cynomolgus monkeys given small molecule immunomodulatory
      antagonists.
AB  - Opportunistic infections (OIs) during the course of non-clinical toxicity studies
      can serve as a clinical indicator of immunosuppression. In monkeys, severity may
      be magnified since the possibility for fecal-oral and cage-to-cage transmission
      of bacteria exists, reserve capacity is low, and clinical signs of infection are
      not easily detected until the infectious process is well underway. This review
      summarizes a case study presented at the HESI-ILSI ITC-Sponsored workshop on
      Naturally Occurring Infections in Non-human Primates and Immunotoxicity
      Implications. It gives an overview on the impact of bacterial infections in
      monkeys on the development and regulatory assessment of three closely-related
      representative small molecule immunomodulatory (anti-inflammatory) drug
      candidates all inhibiting the same drug target. The infections, which sometimes
      progressed to bacteremia and death, originally manifested in the skin, upper
      respiratory tract, gastrointestinal tract, and less frequently as soft tissue
      abscesses. Infections were sporadic and not observed in all studies despite
      coverage of equivalent or higher systemic exposures or longer durations of
      treatment. To address concerns regarding inconsistency in the presentation and
      type of findings and their potential relationship to infection, steps were taken
      to identify causative agents (via culture, microscopy), implement various
      intervention and treatment regimens (supportive care, antibiotics, drug holiday),
      demonstrate reversibility of clinical and immune effects, and study major immune
      components/mechanisms affected (cytokine/stress protein profiling, immune cell
      phenotyping, and humoral/innate immune cell function tests). Appropriate
      diagnosis and characterization of the infection was critical to discrimination of
      these findings as a secondary pharmacologic effect rather than a direct drug
      related target organ effect, and also guided clinical protocol design and
      regulatory acceptance.

PMID- 20136397
TI  - Intrafascial nerve-sparing radical prostatectomy with a laparoscopic robot
      assisted extraperitoneal approach: early oncological and functional results.
AB  - OBJECTIVE: We investigated whether an intrafascial approach to prostatectomy
      would provide significantly improved outcomes compared with retropubic and
      laparoscopic approaches. We performed 50 radical prostatectomies with an
      intrafascial, nerve-sparing, laparoscopic, robot-assisted extraperitoneal
      approach. METHODS: From December 2007 to June 2008, 50 consecutive patients
      underwent nerve sparing surgery using the intrafascial technique with robotic
      assistance. All surgeries were performed by the same senior urologist. Patient
      characteristics and perioperative data were collected prospectively. Oncological
      outcomes were assessed by pathological examination and postoperative prostate
      specific antigen levels. Functional outcomes, including continence, potency, and
      quality of life, were assessed from patient questionnaires. RESULTS: The mean
      operative time was 127 minutes (range: 80-205), the mean hospital stay was 4.2
      days (range: 2-9), and the mean catheterization time was 7.8 days (range: 4-11).
      No perioperative complications occurred. One patient required a transfusion at
      the postoperative stage. The overall positive surgical margin rate was 12%;
      adjusted by tumor, nodes, and metastasis stage, it was 9.5% in pT2 and 17% in pT3
      disease. At the 1-month follow-up, 66% of the patients were continent (no pad),
      12% presented a minimal stress urinary incontinence (1 pad), and 22% required >1
      pad(s) per day. Further, 60% of patients exhibited potency (erection sufficient
      for intercourse: 30% without the use of phosphodiesterase 5 inhibitors, 30%
      required a phosphodiesterase 5 inhibitor) and the remaining 40% required
      prostaglandin injections. CONCLUSIONS: An intrafascial approach with robotic
      assistance provided satisfactory early functional results with respect to
      postoperative continence and potency. Long-term oncological results remain to be
      assessed.

PMID- 20136398
TI  - Ureteroscopic ultrasound technology to size kidney stone fragments: proof of
      principle using a miniaturized probe in a porcine model.
AB  - PURPOSE: A prototype ultrasound-based probe for use in ureteroscopy was used for
      in vitro measurements of stone fragments in a porcine kidney. METHODS: Fifteen
      human stones consisting of three different compositions were placed deep in the
      collecting system of a porcine kidney. A 2 MHz, 1.2 mm (3.6F) needle hydrophone
      was used to send and receive ultrasound pulses for stone sizing. Calculated stone
      thicknesses were compared with caliper measurements. RESULTS: Correlation between
      ultrasound-determined thickness and caliper measurements was excellent in all
      three stone types (r(2) = 0.90, p < 0.0001). All 15 ultrasound measurements were
      accurate to within 1 mm, and 10 measurements were accurate within 0.5 mm.
      CONCLUSION: A 3.6F ultrasound probe can be used to accurately size stone
      fragments to within 1 mm in a porcine kidney.

PMID- 20136399
TI  - Resistance to extrinsic compression and maintenance of intraluminal flow in coil
      reinforced stents (Silhouette Scaffold Device): an in vitro study.
AB  - INTRODUCTION: Stenting is the best approach to manage ureteral extrinsic
      compression and depends on intraluminal patency, which is mainly determined by
      cross-sectional stability. We evaluated the resistance to extrinsic compression
      of the Silhouette Scaffold Device and its ability to simultaneously maintain
      intraluminal flow. MATERIALS AND METHODS: Four 8 F Silhouette stents of different
      lengths were evaluated for radial compression and intraluminal flow by an MTS
      Micro Bionix Testing System using Testworks II software. Compression was exerted
      in 0.2 mm increment cycles until a maximum load cell of 5 N was reached. The
      Young's modulus, E, was calculated from each trial using engineering stress. Flow
      rates were compared with the 10.2 F Cook Amplatz. Analysis of variance was used
      to detect differences between Scaffold stents, and Student's t-test for
      differences between baseline flow rates. A level of significance of p < 0.05 was
      used. RESULTS: Cross-sectional area and E did not differ throughout different
      length Scaffold stents (average 28,856 +/- 2592; 95% confidence interval 27,447,
      30,265; p = 0.426). The inner lumen of the 10.2 F Cook Amplatz was larger by
      0.125 mm. Baseline flow rate of the Cook Amplatz was significantly higher than
      that of the Silhouette Scaffold (1.089 vs. 0.660 mL/second, p = 0.001), but the
      drop in the flow rate was four times faster for the Amplatz. CONCLUSION: The
      resistance of 8 F Silhouette Scaffold Device is extremely higher than that of
      previously tested stents, and it is uniform along the shaft and does not vary
      with length. The Cook Amplatz 10.2 F stent has higher flow at baseline and 2 mm
      compression, but its flow rate drops four times faster than the Silhouette
      Scaffold.

PMID- 20136400
TI  - Delivery of basic fibroblast growth factor using heparin-conjugated fibrin for
      therapeutic angiogenesis.
AB  - Heparin-conjugated fibrin (HCF, a mixture of heparin-conjugated fibrinogen and
      thrombin) was developed as an injectable carrier for long-term delivery of
      fibroblast growth factor 2 (FGF2), and the therapeutic potential of the HCF
      system was investigated by evaluating neovascularization in a mouse hind limb
      ischemia model. HCF released FGF2 for a much longer period than normal fibrin
      containing free heparin in vitro. The FGF2 released from HCF was bioactive, as it
      stimulated growth of human dermal fibroblasts in a serum-depleted medium in
      vitro. In contrast, FGF2 released from normal fibrin did not induce significant
      cell growth, probably because of its short-term release. HCF alone, HCF loaded
      with FGF2, and normal fibrin containing free heparin and FGF2 were implanted into
      mouse ischemic hind limbs for 4 weeks. Histological analysis, Western blot
      analysis, and immunohistological analysis revealed that ischemic limbs treated
      with normal fibrin containing free heparin and FGF2, or treated with HCF only,
      showed severe muscle fibrosis, inflammation, and a low vasculature density. In
      contrast, mice treated with FGF2-loaded HCF showed significantly reduced muscle
      fibrosis and inflammation, and dramatically enhanced neovascularization. FGF2
      delivery using HCF could be useful for therapeutic angiogenesis as HCF delivery
      enhances the therapeutic efficacy of FGF2.

PMID- 20136401
TI  - Improvement on the performance of bone regeneration of calcium sulfate
      hemihydrate by adding mineralized collagen.
AB  - Comparative investigations of bone regeneration performance for calcium sulfate
      hemihydrate (CaSO(4).(1/2)H(2)O; CSH) only and CSH with mineralized collagen are
      reported in this article. The mineralized collagen is the
      nanohydroxyapatite/collagen (nHAC). The investigations included biocompatibility
      in vitro and performance of bone repair in vivo. Quantitative and qualitative
      biocompatibility assays with bone stromal stem cells were performed. A critical
      box-shaped defect model in the mandible of the rabbit was used to evaluate the
      bone-remodeling ability of CSH and nHAC/CSH. Results in vitro indicated that the
      nHAC/CSH significantly improved bioactivity compared with that of CSH, especially
      in promoting cell adhesion. Further, a higher bone remodeling activity was
      observed around nHAC/CSH composite than the CSH, especially at the early stage of
      remodeling. This result means that nHAC/CSH could cause an earlier accelerator
      and better osseointegration for bone repair than CSH only.

PMID- 20136402
TI  - Human embryonic mesodermal progenitors highly resemble human mesenchymal stem
      cells and display high potential for tissue engineering applications.
AB  - Adult stem cells, such as human mesenchymal stem cells (hMSCs), show limited
      proliferative capacity and, after long-term culture, lose their differentiation
      capacity and are therefore not an optimal cell source for tissue engineering.
      Human embryonic stem cells (hESCs) constitute an important new resource in this
      field, but one major drawback is the risk of tumor formation in the recipients.
      One alternative is to use progenitor cells derived from hESCs that are more
      lineage restricted but do not form teratomas. We have recently derived a cell
      line from hESCs denoted hESC-derived mesodermal progenitors (hES-MPs), and here,
      using genome-wide microarray analysis, we report that the process of hES-MPs
      derivation results in a significantly altered expression of hESC characteristic
      genes to an expression level highly similar to that of hMSCs. However, hES-MPs
      displayed a significantly higher proliferative capacity and longer telomeres. The
      hES-MPs also displayed lower expression of HLA class II proteins before and after
      interferon-gamma treatment, indicating that these cells may somewhat be
      immunoprivileged and potentially used for HLA-incompatible transplantation. The
      hES-MPs are thus an appealing alternative to hMSCs in tissue engineering
      applications and stem-cell-based therapies for mesodermal tissues.

PMID- 20136403
TI  - Characterization of ex vivo-generated bovine and human cartilage by
      immunohistochemical, biochemical, and magnetic resonance imaging analyses.
AB  - Osteoarthritis (OA) is a prevalent age-associated disease involving altered
      chondrocyte homeostasis and cartilage degeneration. The avascular nature of
      cartilage and the altered chondrocyte phenotype characteristic of OA severely
      limit the capacity for in vivo tissue regeneration. Cell- and tissue-based repair
      has the potential to revolutionize treatment of OA, but those approaches have
      exhibited limited clinical success to date. In this study, we test the hypothesis
      that bovine and human chondrocytes in a collagen type I scaffold will form
      hyaline cartilage ex vivo with immunohistochemical, biochemical, and magnetic
      resonance (MR) endpoints similar to the original native cartilage. Chondrocytes
      were isolated from 1- to 3-week-old calf knee cartilage or from cartilage
      obtained from human total knee arthroplasties, suspended in 2.7 mg/mL collagen I,
      and plated as 300 microL spot cultures with 5 x 10(6) each. Medium formulations
      were varied, including the amount of serum, the presence or absence of ascorbate,
      and treatments with cytokines. Bovine chondrocytes generated metachromatic
      territorial and interstitial matrix and accumulated type II collagen over time.
      Type VI collagen was confined primarily to the pericellular region. The ex vivo
      formed bovine cartilage contained more chondroitin sulfate per dry weight than
      native cartilage. Human chondrocytes remained viable and generated metachromatic
      territorial matrix, but were unable to support interstitial matrix accumulation.
      MR analysis of ex vivo-formed bovine cartilage revealed evidence of progressively
      maturing matrix, but MR-derived indices of tissue quality did not reach those of
      native cartilage. We conclude that the collagen-spot culture model supports
      formation and maturation of three-dimensional hyaline cartilage from active
      bovine chondrocytes. Future studies will focus on determining the capacity of
      human chondrocytes to show comparable tissue formation.

PMID- 20136404
TI  - Interference of home blood glucose measurements and poor outcomes: a solvable
      problem requiring broader exposure.

PMID- 20136405
TI  - A ray of light for fetal therapy.

PMID- 20136406
TI  - Eosinophilia in a returned traveler.

PMID- 20136408
TI  - Containing the novel influenza A (H1N1) virus.

PMID- 20136409
TI  - The role of interprofessional working in the Pathways to Work Condition
      Management Programmes.
AB  - Condition Management Programmes (CMPs) were established in seven pilot sites in
      the UK as one strand of the Incapacity Benefit Pathways to Work programme, an
      initiative that exemplifies interprofessional working beyond traditional
      healthcare boundaries. The qualitative evaluation of the pilot sites employed a
      realistic evaluation approach and used focus group discussions and telephone
      interviews to examine stakeholders' perceptions of interprofessional working and
      its impact on service provision and practice. Although teething problems were
      experienced in establishing the interprofessional working necessary for success,
      a shared commitment to the CMP ethos enabled these to be largely overcome.
      Outstanding issues raised by participants concerned the boundaries around the
      CMPs' new ways of working, in particular around treatment versus self-management
      and around the combined health and work focus of the pilots. One of the
      recommendations from a recent review of the health of Britain's working
      population was for a drive to promote the understanding of the positive
      relationship between health and work. The experiences of the staff involved in
      the CMP pilots provides a useful insight into the benefits and difficulties
      experienced in relation to interprofessional working between different
      professional groups in this area.

PMID- 20136410
TI  - Adherence with hormone replacement therapy in menopause.
AB  - OBJECTIVE: Lack of adherence to therapy is a common problem in the treatment of
      various diseases and conditions and there are many well-documented reasons for
      it. This study was conducted to assess the effect of time spent on medical
      consultation in relation to the duration of adherence, as well as the reasons to
      adhere to or drop out from hormone replacement therapy (HRT). DESIGN AND METHODS:
      Two methods were used, self-filled questionnaires on a sample of patients and
      telephone interviews on a sample of doctors. The questions dealt with a number of
      personal and gynecological history variables. The participants were chosen using
      random sampling from population lists. A total of 74 participating offices
      recruited all postmenopausal patients, regardless of their HRT use and whether
      they visited the office for a specific complaint or just for a routine check-up.
      The doctors were interviewed regarding the average time spent with a patient,
      prescribing dilemmas and counselling on sexuality. RESULTS: The main finding was
      that the time spent on consultation and the physicians' interest in postmenopause
      critically influence the patients' adherence. The effective time spent with
      patients was in accordance with the National Health Insurance guidelines for
      public sector doctors, but it was twice as long for private sector doctors.
      CONCLUSION: This study shows that extended medical consultation promotes better
      compliance by lowering patient fears, while trusted authorities seem to be more
      convincing to patients on the benefits of HRT and therefore more effective, even
      if they do not take more time to talk to patients.

PMID- 20136411
TI  - Menopausal symptoms within a Hispanic cohort: SWAN, the Study of Women's Health
      Across the Nation.
AB  - INTRODUCTION: Since the designation of people as Hispanic involves the
      amalgamation of a number of different cultures and languages, we sought to test
      the hypothesis that menopausal symptoms would differ among Hispanic women, based
      upon country of origin and degree of acculturation. METHODS: A total of 419
      women, aged 42-52 years at baseline, were categorized as: Central American (CA, n
      = 29) or South American (SA, n = 106), Puerto Rican (PR, n = 56), Dominican (D, n
      = 42), Cuban (Cu, n = 44) and non-Hispanic Caucasian (n = 142). We assessed
      vasomotor symptoms, vaginal dryness and trouble in sleeping. Hispanics and non
      Hispanic Caucasians were compared using the chi(2) test, t test or non-parametric
      alternatives; ANOVA or Kruskal-Wallis testing examined differences among the five
      Hispanic sub-groups. Multivariable regression models used PR women as the
      reference group. RESULTS: Hispanic women were overall less educated, less
      acculturated (p < 0.001 for both) than non-Hispanic Caucasians and more of them
      reported vasomotor symptoms (34.1-72.4% vs. 38.3% among non-Hispanic Caucasians;
      p = 0.0293) and vaginal dryness (17.9-58.6% vs. 21.1% among non-Hispanic
      Caucasians, p = 0.0287). Among Hispanics, more CA women reported vasomotor
      symptoms than D, Cu, SA, or PR women (72.4% vs. 45.2%, 34.1%, 50.9%, and 51.8%,
      respectively). More CA (58.6%) and D women (38.1%) reported vaginal dryness than
      PR (17.9%), Cu (25.0%) and SA (31.4%) women. More PR and D women reported trouble
      in sleeping (66.1 and 64.3%, respectively) compared to CA (51.7%), Cu (36.4%),
      and SA (45.3%) women. CONCLUSION: Symptoms associated with menopause among
      Hispanic women differed by country of origin but not acculturation. Central
      American women appear to be at greatest risk for both vasomotor symptoms and
      vaginal dryness.

PMID- 20136412
TI  - Mutations in extensively drug-resistant Mycobacterium tuberculosis that do not
      code for known drug-resistance mechanisms.
AB  - BACKGROUND: Highly lethal outbreaks of multidrug-resistant (MDR) and extensively
      drug-resistant (XDR) tuberculosis are increasing. Whole-genome sequencing of
      KwaZulu-Natal MDR and XDR outbreak strains prevalent in human immunodeficiency
      virus (HIV)-infected patients by the Broad Institute identified 22 novel
      mutations which were unique to the XDR genome or shared only by the MDR and XDR
      genomes and not already known to be associated with drug resistance. METHODS: We
      studied the 12 novel mutations which were not located in highly-repetitive genes
      to identify mutations that were truly associated with drug resistance or were
      likely to confer a specific fitness advantage. RESULTS: None of these mutations
      could be found in a phylogenetically and geographically diverse set of drug
      resistant and drug-susceptible Mycobacterium tuberculosis isolates, suggesting
      that these mutations are unique to the KZN clone. Examination of the 600-basepair
      region flanking each mutation revealed 26 new mutations. We searched for a
      convergent evolutionary signal in the new mutations for evidence that they
      emerged under selective pressure, consistent with increased fitness. However, all
      but 1 rare mutation were monophyletic, indicating that the mutations were markers
      of strain phylogeny rather than fitness or drug resistance. CONCLUSIONS: Our
      results suggest that virulent XDR tuberculosis in immunocompromised HIV-infected
      patients can evolve without generalizable fitness changes or other XDR-specific
      mutations.

PMID- 20136413
TI  - Low-level CD4+ T cell activation in HIV-exposed seronegative subjects: influence
      of gender and condom use.
AB  - Immune activation has been suggested to increase susceptibility to human
      immunodeficiency virus type 1 (HIV-1) transmission, while at the same time it
      could be deemed essential for mounting an effective antiviral immune response. In
      this study, we compared levels of T cell activation between exposed seronegative
      (ESN) partners in HIV-1 discordant couples and HIV-unexposed control subjects in
      Dakar, Senegal. ESN subjects showed lower levels of CD38 expression on CD4(+) T
      cells than did control subjects. However, this was found to be associated with
      concurrent differences in the use of condoms: ESN subjects reported a higher
      degree of condom use than did control subjects, which correlated inversely with
      CD38 expression. In addition, we observed markedly higher levels of T cell
      activation in women compared with men, irrespective of sexual behavior. These
      findings question the relevance of low-level CD4(+) T cell activation in
      resistance to HIV-1 infection and underscore the need to take gender and sexual
      behavior characteristics of high-risk populations into account when analyzing
      correlates of protective immunity.

PMID- 20136414
TI  - A piglet model of acute gastroenteritis induced by Shigella dysenteriae Type 1.
AB  - BACKGROUND: The lack of a standardized laboratory animal model that mimics key
      aspects of human shigellosis remains a major obstacle to addressing questions
      about pathogenesis, screening therapeutics, and evaluation of vaccines. METHODS:
      We characterized a piglet model for Shigella dysenteriae type 1. RESULTS: Piglets
      developed acute diarrhea, anorexia, and dehydration, which could often be fatal,
      with symptom severity depending on age and dose. Bacteria were apparent in the
      lumen and on the surface epithelium throughout the gut initially, but severe
      mucosal damage and bacterial cellular invasion were most profound in the colon.
      Detached necrotic colonocytes were present in the lumen, with inflammatory cells
      outpouring from damaged mucosa. High levels of interleukin (IL)-8 and IL-12 were
      followed by high levels of other proinflammatory cytokines. Elevated levels of
      tumor necrosis factor-alpha, IL-1beta, IL-6, and IL-10 were detected in feces and
      in gut segments from infected animals. Bacteria were present inside epithelial
      cells and within colonic lamina propria. In contrast, an isogenic strain lacking
      Shiga toxin induced similar but milder symptoms, with moderate mucosal damage and
      lower cytokine levels. CONCLUSION: We conclude that piglets are highly
      susceptible to shigellosis, providing a useful tool with which to compare vaccine
      candidates for immunogenicity, reactogenicity, and response to challenge;
      investigate the role of virulence factors; and test the efficacy of microbial
      agents.

PMID- 20136415
TI  - Delayed clearance of viral load and marked cytokine activation in severe cases of
      pandemic H1N1 2009 influenza virus infection.
AB  - BACKGROUND: Infections caused by the pandemic H1N1 2009 influenza virus range
      from mild upper respiratory tract syndromes to fatal diseases. However, studies
      comparing virological and immunological profile of different clinical severity
      are lacking. METHODS: We conducted a retrospective cohort study of 74 patients
      with pandemic H1N1 infection, including 23 patients who either developed acute
      respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with
      desaturation requiring oxygen supplementation and who survived without ARDS
      (survived-without-ARDS group), and 37 patients with mild disease without
      desaturation (mild-disease group). We compared their pattern of clinical disease,
      viral load, and immunological profile. RESULTS: Patients with severe disease were
      older, more likely to be obese or having underlying diseases, and had lower
      respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death
      group had a slower decline in nasopharyngeal viral loads, had higher plasma
      levels of proinflammatory cytokines and chemokines, and were more likely to have
      bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than
      patients in the survived-without-ARDS or the mild-disease groups. Reactive
      hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar
      damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1
      infection were found at postmortem examinations. CONCLUSIONS: The slower control
      of viral load and immunodysregulation in severe cases mandate the search for more
      effective antiviral and immunomodulatory regimens to stop the excessive cytokine
      activation resulting in ARDS and death.

PMID- 20136416
TI  - HIV treatment guidelines revised.

PMID- 20136417
TI  - Obesity may adversely affect HIV treatment.

PMID- 20136418
TI  - Intravitreal bevacizumab in treatment of idiopathic persistent central serous
      chorioretinopathy: a prospective, controlled clinical study.
AB  - PURPOSE: To evaluate and determine the effect of intravitreal bevacizumab in
      treatment of persistent central serous chorioretinopathy. METHODS: This
      prospective, comparative clinical study included 30 eyes of 30 patients with
      persistent, symptomatic central serous chorioretinopathy of 3 months' duration or
      more. Fifteen eyes of 15 patients were treated with intravitreal injections of
      2.5 mg (0.1 ml) bevacizumab (treatment group). Fifteen eyes of 15 patients with
      the same characteristics who declined treatment were an acceptable control group.
      The visual and anatomic responses were observed with best-corrected visual acuity
      and central foveal thickness measured by optic coherence tomography at
      baseline,1, 3, and 6 months after treatment. RESULTS: Twelve (80%) eyes in the
      treatment group compared with 8 (53.3%) eyes in the control group showed
      morphologic restitution at 6 months (P < 0.01). All 15 (100%) treated eyes had
      stable or improved vision, compared with 10 (66.6%) eyes in the control group (P
      < 0.01). At 6 months, the mean +/- SD central foveal thickness for the treatment
      group remained significantly lower compared to the control group, with 174 +/- 68
      microm and 297 +/- 172 microm, respectively (P < 0.001). Injection-related
      complications were not encountered. CONCLUSIONS: Our results indicate that
      intravitreal bevacizumab injection may be a new, promising treatment option for
      select patients with idiopathic persistent central serous chorioretinopathy.
      Continued studies with intravitreal bevacizumab in this population will help to
      establish its long-term efficacy.

PMID- 20136419
TI  - Broccoli regulates protein alterations and cataractogenesis in selenite models.
AB  - PURPOSE: To study the efficacy of Brassica oleracea var. italica (Broccoli) in
      the prevention of selenite induced biochemical changes and the incidence of
      cataractogenesis in vivo. METHODS: Eight day old Sprague-Dawley rat pups were
      divided into four groups: I-Control; II-Sodium selenite (4 mg/kg body weight)
      administered; III-Sodium selenite + quercetin; and IV-Sodium selenite + flavonoid
      fraction of broccoli (FFB). Treatment groups III and IV received quercetin and
      FFB intraperitoneally from 8th to 15th day at a concentration (2.0 mg/kg body
      weight). The development of cataract was assessed and graded by slit-lamp
      examination. Some relevant biochemical parameters-such as activities of
      superoxide dismutase (SOD), catalase, Ca(2+)ATPase, calpains, concentration of
      reduced glutathione (GSH), levels of calcium, lipid peroxidation product
      thiobarbituric acid reacting substances (TBARS) and SDS-PAGE analysis of lens
      water soluble proteins (WSF) were analyzed. RESULTS: FFB modulates selenite
      induced biochemical changes in albino rats. Lenses of Group I rats were clear but
      in Group II, all lenses developed dense opacification (grade 5 and 6), whereas
      mild opacifications were observed in Group III and Group IV (grade 2). Group III
      and Group IV lenses exhibited significantly higher values of antioxidant enzymes,
      Ca(2+)ATPase, and GSH, whereas lower values were obtained for TBARS, calcium, and
      calpains compared to Group II. Lens protein profile of water soluble proteins
      showed normal levels of Group III and Group IV compared to Group II lenses.
      CONCLUSION: FFB prevents selenite-induced cataractogenesis in albino rat pups,
      possibly by maintaining antioxidant status and ionic balance through Ca(2+)
      ATPase pump, inhibition of lipid peroxidation, calpain activation, and protein
      insolubilization, which have been reported in this article for the first time.

PMID- 20136420
TI  - Effect of subconjunctival and intraocular bevacizumab injections on corneal
      neovascularization in a mouse model.
AB  - PURPOSE: This study sought to evaluate the efficacy of bevacizumab (Avastin), an
      anti-VEGF agent, in the reduction of corneal neovascularization in a rodent
      model, and compare between the effect of intraocular and subconjunctival
      injection. METHODS: Corneal neovascularization was induced by application of a
      mixture of 75% silver nitrate and 25% potassium nitrate to the corneal center of
      the right eye of 125 mice. Immediately thereafter, 75 eyes were treated with
      subconjunctival, anterior chamber, or intravitreal injection of bevacizumab. The
      remaining mice served as a control. The groups were compared at different
      postoperative time points for percentage area of neovascularization evaluated by
      digital photos, the presence of corneal stromal vascular endothelial cells
      studied by immunohistochemical staining, and VEGF levels measured by real-time
      PCR. RESULTS: In the untreated eyes, percentage area of neovascularization
      increased from 11.3 +/- 7% on day 2 to 20 +/- 8.9% on day 4, 47 +/- 25.4% on day
      8, and 51 +/- 24.7% on day 10. The percentage area of neovascularization
      following subconjunctival injection was 7 +/- 2.9% on day 2, 15.7 +/- 6% on day
      4, 32.2 +/- 15.2% on day 8, and 39.7 +/- 14.5% on day 10. The percentage area of
      neovascularization following anterior chamber injection was 14.4 +/- 3% on day 2,
      16.5 +/- 6.3% on day 4, 26.3 +/- 6.5% on day 8, and 19.8 +/- 1.2% on day 10. The
      percentage area of neovascularization following intravitreal injection was 11 +/-
      2.5% on day 2, 14.7 +/- 5% on day 4, 23.5 +/- 6.5% on day 8, and 24.2 +/- 14.9%
      on day 10. CONCLUSIONS: Bevacizumab injections partially inhibit the growth of
      corneal neovascularization induced by acute chemical injury in a mouse model. The
      intraocular routes of injection were found to be the most effective, and the
      subconjunctival route of injection yielded the earliest peak response.

PMID- 20136421
TI  - Corneal distribution of riboflavin prior to collagen cross-linking.
AB  - PURPOSE: To evaluate the distribution of riboflavin in the corneal stroma, under
      varying concentrations and application time. MATERIALS AND METHODS: In 54 porcine
      eyes, the central corneal epithelium was removed, and 0.035, 0.1, or 0.2%
      riboflavin-5-phosphate (in 20% Dextran T-500) was applied for 10, 20, or 30 min
      (3 x 6 corneas in each of the 3 groups). Trephined corneal buttons were examined
      using confocal fluorescence microscopy. Stromal riboflavin distribution and
      concentration was determined by measuring riboflavin fluorescence in optical
      sections at 10 microm intervals through the entire cornea. The procedure was
      repeated in 7 human corneal donor grafts using 0.1% riboflavin-5-phosphate for 20
      or 30 min. RESULTS: In porcine corneas, fluorescence intensity peaked within the
      first 50 microm followed by a steep decline to baseline. Increasing the
      riboflavin concentration from 0.1 to 0.2% did not increase stromal depth
      propagation, although a higher concentration in the anterior 200 microm was
      observed. Reducing the riboflavin application time from 30 to 20 min had no
      impact on corneal depth propagation or total riboflavin uptake. However, a 10-min
      further reduction of the application time caused a significantly reduced
      riboflavin uptake. In all human corneas, fluorescence peaked within the anterior
      50 microm, followed by a steep decline to baseline over the next 200 microm;
      similar to the observations in porcine corneas. The human corneas imbibed more
      riboflavin compared to the porcine corneas. CONCLUSIONS: In human and porcine
      corneas, riboflavin does not appear to fully load the corneal stroma using the
      current clinical procedure. Instead, the uptake appears to be limited to the
      anterior approximately 200 microm. Changes in application time and riboflavin
      concentration have only little influence on stromal depth diffusion.

PMID- 20136422
TI  - Effect of curcumin on selenite-induced cataractogenesis in Wistar rat pups.
AB  - PURPOSE: The present study was aimed at investigating the possible antioxidant
      potential of curcumin at a dose of 75 mg/kg body weight on selenite-induced
      cataract in experimental rat pups. METHODS: Group I: Control rat pups receiving
      physiological saline; Group II: Selenite-induced group (15 microM/kg body wt);
      Group III: Selenite-induced group co-treated with curcumin (single dose of
      curcumin orally 75 mg/kg body wt); Group IV: Selenite-induced animals post
      treated (after 24 hrs) with curcumin at a dose mentioned for group III; Group V:
      Rat pups were pretreated with curcumin (dose as mentioned in Group III), 24 hrs
      before the administration of selenite. Encapsulated lenses liver, kidney, and
      serum were analyzed for antioxidant enzymes and malondialdehyde, a marker of
      lipid peroxidation. RESULTS: Intraperitoneal injection of sodium selenite (15
      microM/kg body wt) to 8-10-day-old rat pups led to severe oxidative stress in eye
      lens as evidenced by enhanced LPO levels that led to cataract formation. Sodium
      selenite also led to decrease in activities of SOD, GST, GPx, CAT with
      simultaneous decrease in the levels of GSH, vitamin C, and vitamin E. Treatment
      with curcumin (75 mg/kg body wt) led to a significant decrease in the levels of
      LPO, enzymic antioxidants, and nonenzymic antioxidants, which were similar to
      that of control. CONCLUSIONS: Curcumin suppressed selenite-induced oxidative
      stress and cataract formation in rat pups. The presence of oxidative stress in
      selenite cataract development and its prevention by curcumin support the
      possibility that the natural consumption of curcumin in food can help prevent the
      onset of senile cataract.

PMID- 20136423
TI  - Refractive error may influence mesopic pupil size.
AB  - PURPOSE: To identify factors which affect mesopic pupil diameter in refractive
      surgery patients. SETTING: This retrospective study was performed at the 1st
      Ophthalmology Clinic in Ankara Ataturk Training and Research Hospital, Ankara,
      Turkey. METHODS: Medical records of 412 refractive surgery candidates who applied
      between 2006 and 2008 were reviewed. Detailed ophthalmological examination data
      were obtained from medical records. Pupil size measurements were performed with a
      COAS Ocular Wavefront analyzer in mesopic conditions. Relationship between
      mesopic pupil diameter and age, sex, spherical refractive error (D), magnitude of
      astigmatism (D), type of astigmatism, spherical equivalent, and average
      keratometry were analyzed by means of univariate and multivariate regression
      analyses. RESULTS: Mean mesopic pupil diameter was 6.19 +/- 0.88 mm. Mean pupil
      diameter (mean +/- standard deviation) was 5.70 +/- 1.01 in hypermetropia, 6.04
      +/- 0.79 mm in mixed astigmatism, and 6.33 +/- 0.82 mm in myopia. The difference
      in mean mesopic pupil diameters between myopes and hypermetropes was
      statistically significant (p = 0.001). However, differences with regard to mean
      pupil diameters between myopes and mixed astigmatism (p = 0.660) and between
      hypermetropes and mixed astigmatism (p = 0.109) were not significant. Mean pupil
      diameter was 6.00 +/- 0.99 mm in against the rule astigmatism, 5.96 +/- 0.84 mm
      in oblique astigmatism, and 6.27 +/- 0.84 mm in with the rule astigmatism. Mean
      mesopic pupil diameter in with the rule astigmatism group was higher than oblique
      astigmatism group. Spherical refractive error (r = -0.213, p = 0.001),
      cylindrical refractive error (0.197, p = 0.001), and age (r = -0.341, p = 0.001)
      showed correlation with pupil diameter. CONCLUSIONS: This study showed that age
      and magnitude of both spherical and cylindrical refractive error are the most
      determinative factors on mesopic pupil size.

PMID- 20136424
TI  - IRD1 and IRD2 mice, naturally occurring models of hereditary retinal dysfunction,
      show late-onset and progressive retinal degeneration.
AB  - PURPOSE: To elucidate whether Institute for Cancer Research (ICR) derived retinal
      dysfunction (IRD) 1 and IRD2 mice, spontaneous mouse models of rod-cone and rod
      dysfunction, respectively, develop age-related retinal degeneration. MATERIALS
      AND METHODS: Morphological and morphometric examinations were performed in the
      retinas of both mutants from 1 to 18 months of age. The rate of apoptotic cell
      death was determined by TUNEL techniques. Electroretinography was performed on
      the IRD2 mice at various ages. Age-matched ICR mice were used as controls.
      RESULTS: IRD1 and IRD2 mice showed a decrease in the thickness of the outer
      nuclear layer and a higher frequency of TUNEL-positive photoreceptor cells at 6
      months of age compared with controls, and showed almost complete absence of the
      outer nuclear layer at 18 months of age. Light deprivation had no effect on the
      severity of the retinal degeneration. There were no differences in the number of
      cone nuclei among ICR, IRD1, and IRD2 mice at 12 months of age and the cones of
      the IRD2 mice were still functional at this age. CONCLUSIONS: IRD1 and IRD2 mice
      showed late-onset and progressive retinal degeneration.

PMID- 20136425
TI  - Aldose reductase inhibitor fidarestat attenuates leukocyte-endothelial
      interactions in experimental diabetic rat retina in vivo.
AB  - PURPOSE: Dysregulation of the polyol pathway has been implicated as a major cause
      of diabetic retinopathy. The aldose reductase inhibitor fidarestat was recently
      reported to prevent retinal oxidative stress and overexpression of vascular
      endothelial growth factor (VEGF) protein in diabetic rats. In this study, we
      investigated the effect of fidarestat on leukocyte-endothelial cell interactions
      in an in vivo experimental model for diabetic retina. MATERIALS AND METHODS:
      Diabetes was induced in six-week-old male Long-Evans rats by intraperitoneal
      injection of streptozotocin (STZ) (75 mg/kg). The rats were divided into four
      experimental groups: non-diabetic control rats, untreated diabetic rats, and
      diabetic rats treated with a low (4 mg/kg/day) or high (16 mg/kg/day) oral dose
      of fidarestat. After four weeks of treatment, accumulated leukocytes in the
      retina were counted in vivo by acridine orange digital fluorography.
      Intercellular adhesion molecule-1 (ICAM-1) and VEGF-164 mRNA levels in the retina
      were analyzed using the quantitative reverse transcription-polymerase chain
      reaction. ICAM-1 protein expression in the retina was investigated by
      immunohistochemistry. RESULTS: Fidarestat treatment significantly decreased
      concentrations of sorbitol and fructose in the retinas of STZ-induced diabetic
      rats. Leukocyte accumulation in the retinas of fidarestat-treated rats was
      significantly less than in the untreated diabetic group (P < 0.01). Fidarestat
      treatment significantly reduced the expression ICAM-1 mRNA, but not VEGF-164
      mRNA, in the retina of diabetic rats. Immunohistochemical study also revealed the
      suppressive effect of fidarestat on expression of ICAM-1. CONCLUSIONS: Oral
      administration of fidarestat attenuated leukocyte accumulation in the retina of
      STZ induced-diabetic rats, suggesting that fidarestat may have a therapeutic role
      in preventing the progression of diabetic retinopathy.

PMID- 20136426
TI  - Correlation between photopic negative response of focal electroretinograms and
      local loss of retinal neurons in glaucoma.
AB  - PURPOSE: To determine the relationship between the photopic negative response of
      the focal electroretinogram and the structural parameters of the inner retina and
      optic nerve head in glaucoma. METHODS: Sixty-one eyes of 61 patients with open
      angle glaucoma, 13 eyes of 13 patients who were classified as glaucoma suspects,
      and 30 eyes of 30 normal subjects were studied. The focal electroretinograms were
      elicited by a 15 degrees circular white stimulus on a white background centered
      on the fovea. The focal electroretinograms were also elicited by half of an
      annulus placed above or below the macula. The diameter of the inner border of the
      annulus was 15 degrees and that of the outer border was 30 degrees. The structure
      of the optic nerve head and retinal nerve fiber layer thickness were evaluated by
      scanning laser ophthalmoscopy and laser scanning polarimetry, respectively.
      RESULTS: The amplitudes of the focal photopic negative responses and the ratio of
      the focal photopic negative response/b-wave amplitude were linearly correlated
      with the corresponding retinal nerve fiber layer thickness in the
      superior/temporal and inferior/temporal regions (r = 0.43 to 0.47; P < 0.0001)
      but not in the temporal region. The focal photopic negative response amplitude
      and focal photopic negative response/b-wave amplitude ratio were also linearly
      and significantly correlated with the corresponding rim areas and cup/disc area
      ratio (r = 0.38 to 0.50, P < 0.0001). CONCLUSIONS: These results strongly suggest
      that the anatomical losses of retinal neurons in local areas of the retina or
      optic nerve head are a cause of the reduction in the amplitude of the focal
      photopic negative response in open angle glaucoma.

PMID- 20136427
TI  - The therapeutic effect of DA-6034 on ocular inflammation via suppression of MMP-9
      and inflammatory cytokines and activation of the MAPK signaling pathway in an
      experimental dry eye model.
AB  - PURPOSE: To investigate the effect of DA-6034, 7-carboxymethyloxy-3',4',5
      trimethoxy flavone, in experimentally-induced inflammatory dry eye in rabbit. In
      addition, to elucidate the mechanism of DA-6034, we evaluated the mitogen
      activated protein kinase (MAPK) signaling pathway and transcriptional factor
      kappa B (NF-kB) in corneal epithelial cells. METHODS: Rabbit lacrimal glands were
      injected with the T-cell mitogen concanavalin A (Con A). DA-6034 was then
      administered topically four times a day for six days starting 24 hr after Con A
      injection. Tear volume, tear function, MMP-9 and inflammatory cytokine levels in
      the lacrimal glands, and histological evaluation were subsequently assessed. In
      in vitro study, phosphorylated MAPKs (c-Jun NH2-terminal kinase (JNK) and p38
      MAPK) and NF-kB were detected by enzyme-linked immunosorbent assay (ELISA) using
      human corneal epithelial cells. RESULTS: A single injection of Con A into the
      lacrimal glands induced a pronounced inflammatory response, caused elevated
      levels of MMP-9 and cytokines IL-8 and TGF-beta(1), and induced a decrease in
      tear volume and shortening of tear breakup time (TBUT). In this inflammation
      model of dry eye, DA-6034 clearly showed therapeutic efficacy by restoring tear
      function and inhibiting inflammatory responses after topical ocular application.
      Furthermore, DA-6034 attenuated the phosphorylation of JNK and p38 MAPK and
      inhibited NF-kB activation in a concentration-dependent manner in corneal
      epithelial cells. CONCLUSIONS: These results suggest that DA-6034 has the
      therapeutic effect in rabbit lacrimal gland inflammation model of dry eye and
      might be a potential treatment option for acute dry eye syndrome.

PMID- 20136428
TI  - Active in vitro reduction of antigen presenting cells in human corneal grafts
      using different chemokines.
AB  - BACKGROUND: For the fate of a graft the antigen presenting cells play an
      important role. Chemokines can lead to enhanced migration of these cells. We
      therefore investigated if fresh human corneas bear the chemokine receptor 7
      (CCR7) and if its ligands can force the emigration of dendritic cells in an in
      vitro model. METHODS: We used human corneas excluded for transplantation and
      performed migration tests using chemokine ligands 19 (CCL19) and 21 (CCL21) or
      the complement factor 5a (C5a). Emigrated cells were collected up to 35 days and
      stained by immunofluorescent double labeling in triple layer technique with
      Langerin/CD207, DC-SIGN/CD209, CD14, and HLA-DR. In parallel, fresh and cultured
      human corneas were stained for CCR7. RESULTS: We found in fresh human corneas, as
      well as in long-term cultured ones, a low CCR7 expression that nearly diminished
      after 28 days. In vitro Langerhans cell emigration could be enhanced only by
      CCL19, whereas dendritic cells were strongly influenced by CCL19, CCL21, and C5a.
      HLA-DR(+) cells showed numerically the highest in vitro emigration rate.
      Macrophages/monocytes were not influenced by the used chemokines. CONCLUSIONS:
      Although human corneas reduce their antigen presenting cells numbers during long
      term culture, this effect could be significantly enhanced by using chemokines.

PMID- 20136429
TI  - A lipid-soluble red ginseng extract inhibits the growth of human lung tumor
      xenografts in nude mice.
AB  - Lipid-soluble ginseng extract was prepared by n-hexane extraction of red ginseng.
      BALB/c-nu mice were inoculated with human lung cancer (NCI-H460) cells to
      establish a human tumor xenograft model in nude mice, and the lipid-soluble
      ginseng extract was orally administered. The tumor inhibitory rates of the lipid
      soluble ginseng extract at doses of 0.1, 0.3, and 1.0 g/kg/day were 18.9% (P <
      .05), 60.0% (P < .001), and 67.5% (P < .001), respectively. The oral
      administration of the lipid-soluble extract of red ginseng showed a potent
      anticancer effect in nude mice bearing human lung cancer cells in a dose
      dependent manner without any apparent toxicity. This lipid-soluble ginseng
      extract is a potential nontoxic anticancer supplement for the prevention and
      intervention of lung tumor growth through an oral administration route.

PMID- 20136430
TI  - Antiproliferative effect of chitosan-added kimchi in HT-29 human colon carcinoma
      cells.
AB  - The anticancer effects of chitosan-added kimchi were investigated by using an in
      vitro cellular system with HT-29 human colon carcinoma cells. Two different kinds
      of chitosan-soluble chitosan with a 90% degree of deacetylation and 3 cps
      viscosity and nonsoluble chitosan with a 95% degree of deacetylation and 22 cps
      viscosity-were used as sub-ingredients to increase anticancer effects of kimchi.
      The soluble chitosan-added kimchi (SK) and nonsoluble chitosan-added kimchi (NK)
      were stronger growth inhibitors in HT-29 cells than the control kimchi (CK)
      according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay and the growth inhibition test. Treatment with SK and NK induced apoptosis,
      as determined by 4,6-diamidino-2-phenylindole staining, and resulted in the up
      regulation of Bax expression and down-regulation of Bcl-2, cIAP-1, cellular
      inhibitor of apoptosis-2, cyclooxygenase-2, inhibitory nitric oxide synthase, and
      nuclear factor kappaB (NF-kappaB) expressions when compared to CK. The
      antiproliferative and anti-apoptotic effects appeared to be more pronounced in
      the cells treated with NK. The antiproliferative effects of the chitosan-added
      kimchi appeared to be associated with the induction of apoptosis through NF
      kappaB or an NF-kappaB-dependent pathway. These results suggest that chitosan has
      potential to be a valuable active ingredient in functional kimchi products with
      anticancer effects.

PMID- 20136431
TI  - trans-10,cis-12 conjugated linoleic acid inhibits insulin-like growth factor-I
      receptor signaling in TSU-Pr1 human bladder cancer cells.
AB  - Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers
      of linoleic acid; the major isomers are trans-10,cis-12 CLA (t10c12) and cis
      9,trans-11 CLA (c9t11). CLA has been demonstrated to exert strong
      anticarcinogenic effects in a variety of experimental cancer models. We
      previously observed that CLA (a mixture of isomers) and t10c12 decreased the
      growth of TSU-Pr1 cells, whereas linoleic acid and c9t11 exerted no effects. In
      the current study, the mechanisms underlying the t10c12-mediated regulation of
      the growth of these bladder cancer cells were evaluated. TSU-Pr1 cells were
      incubated in serum-free medium with various concentrations of t10c12 or c9t11 in
      the presence or absence of insulin-like growth factor (IGF)-I. The incorporation
      of [(3)H]thymidine into DNA was decreased, and the number of annexin V-stained
      cells was increased after t10c12 treatment, whereas c9t11 had no effect on
      apoptosis or [(3)H]thymidine incorporation. Treatment with exogenous IGF-I alone
      increased the numbers of viable cells but did not counteract the t10c12-induced
      growth inhibition of TSU-Pr1 cells. t10c12 effected a dose-dependent reduction in
      IGF-I receptor (IGF-IR) transcripts and protein levels, whereas c9t11 exerted no
      effects. Additionally, t10c12 inhibited the IGF-I-induced phosphorylation of IGF
      IR, the recruitment of the p85 regulatory subunit of phosphoinositide 3-kinase to
      IGF-IR, and the phosphorylation of Akt and extracellular signal-regulated kinase
      (ERK)-1/2. These results indicate that the inhibition of IGF-IR signaling and the
      activation of Akt and ERK-1/2 contributed to decreased cell proliferation and
      increased apoptosis in TSU-Pr1 cells treated with t10c12.

PMID- 20136432
TI  - Potential antitumor activity of a low-molecular-weight protein fraction from
      Grifola frondosa through enhancement of cytokine production.
AB  - Edible mushrooms contain an abundance of immune-enhancing nutritients. Some of
      these compounds, referred to as biological response modifiers (BRMs), have been
      used in biological therapies for cancer treatment. We obtained a low-molecular
      weight protein fraction (MLP-Fraction) from the fruiting body of the maitake
      mushroom Grifola frondosa by multiple sequential steps, including ethanol
      precipitation, DEAE-exchange chromatography, and gel filtration. The effect of
      the MLP-Fraction on the immune system was determined using normal mice. This
      resulted in a simultaneous increase in splenocyte proliferation and production of
      cytokines such as interleukin (IL)-1alpha, tumor necrosis factor-alpha, IL-10, IL
      12, and interferon (IFN)-gamma. The expression levels of IFN-gamma and IL-12 in
      antigen-presenting cells (APCs) and the activation of natural killer (NK) cells,
      macrophages, and dendritic cells were observed. These results suggest a mechanism
      in which NK cells are activated through cytokines produced by APCs. We also
      confirmed the possibility that the MLP-Fraction acts as a BRM using colon-26
      carcinoma-bearing mice. This fraction enhanced the production of IL-12 and IFN
      gamma by splenocytes in tumor-bearing mice and clearly showed an inhibitory
      effect on tumor cell growth.

PMID- 20136433
TI  - The ethyl alcohol extract of Hizikia fusiforme inhibits matrix metalloproteinase
      activity and regulates tight junction related protein expression in Hep3B human
      hepatocarcinoma cells.
AB  - We tested the correlation between the tightness of tight junctions (TJs) and the
      anti-invasive activity of the ethyl alcohol extract of Hizikia fusiforme (EHF) in
      Hep3B human hepatocarcinoma cells. EHF inhibited cell proliferation, motility,
      and invasiveness, which were associated with increased TJ tightness, as
      demonstrated by an increase in transepithelial electrical resistance. EHF dose
      dependently decreased the secretion of matrix metalloprotease-2 and -9, which
      correlated with a decrease in mRNA and protein expression, but increased tissue
      inhibitor of metalloproteinase-1 and -2 mRNA levels. Additionally, immunoblotting
      results indicated that EHF suppressed the major components of TJ, claudins (-1, 
      3, and -4), which play a key role in the control and selectivity of paracellular
      transport. These data indicate that EHF may inhibit cancer cell invasion through
      the tightening of TJs, which may counteract the up-regulation of claudins.
      Furthermore, EHF treatment decreased the expression of insulin-like growth factor
      1 receptor proteins, while concurrently increasing that of thrombospondin-1 and E
      cadherin. In conclusion, these results suggest that EHF treatment may inhibit
      tumor metastasis and invasion and therefore act as a dietary resource for
      decreasing the risk of developing cancer.

PMID- 20136434
TI  - The chemopreventive effects of Carpesium abrotanoides are mediated by induction
      of phase II detoxification enzymes and apoptosis in human colorectal cancer
      cells.
AB  - Cancer chemoprevention is thought to occur either by blocking the initiation of
      or suppressing the promotion of carcinogenesis. Phase II detoxification enzymes
      are known to play important roles in cancer chemoprevention because they enhance
      cytoprotection through detoxification and elimination of activated carcinogens at
      tumor initiation. Apoptosis is one of the most important inhibitory targets for
      tumor promotion. In this study, we have investigated the cancer chemopreventive
      activity of the ethanolic extract of Carpesium abrotanoides (CAE). We found that
      CAE induced quinone reductase [also known as NAD(P)H:quinone oxidoreductase
      (NQO1)] activity, increased NQO1 mRNA and protein expression, and had a
      relatively high chemoprevention index (12.04). CAE also significantly activated
      the antioxidant response element through the nuclear accumulation of NF-E2
      related factor 2 in HCT116. Interestingly, we also found that CAE induced
      apoptosis, as evidenced by the externalization of phosphatidylserine, increased
      sub-G(0)/G(1) content, chromatin condensation, poly(ADP-ribose) polymerase
      cleavage, and p53. These data suggest that the chemopreventive effects of C.
      abrotanoides can result from both the induction of phase II detoxification
      enzymes and from apoptosis. Thus, CAE could potentially be developed as a cancer
      chemopreventive agent for prevention or treatment of human cancers.

PMID- 20136435
TI  - HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in
      tumor-bearing mice.
AB  - Although radiotherapy is commonly used for a variety of cancers, radiotherapy
      alone does not achieve a satisfactory therapeutic outcome. In this study, we
      examined the possibility that HemoHIM can enhance the anticancer effects of
      ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by
      adding the ethanol-insoluble fraction to the total water extract of a mixture of
      three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer
      effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR
      treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of
      the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in
      tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM
      administration also increased the activity of natural killer cells and cytotoxic
      T cells, although the proportions of these cells in spleen were not different. In
      addition, HemoHIM administration increased the interleukin-2 and tumor necrosis
      factor-alpha secretion from lymphocytes stimulated with concanavalin A, which
      seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice
      treated with IR. In conclusion, HemoHIM may be a beneficial supplement during
      radiotherapy for enhancing the antitumor efficacy.

PMID- 20136436
TI  - Antiproliferative and antitumorigenic activity of Toona sinensis leaf extracts in
      lung adenocarcinoma.
AB  - Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis
      leaf possess a variety of biological functions. This study attempted to test the
      antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441
      cells (lung adenocarcinoma). The data showed that the antiproliferative effect of
      TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell
      morphology, sub-G(1) peak accumulation, cleavage of poly(ADP)-ribose polymerase,
      and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2
      accompanied by increased Bax (in western blotting) was found with TSL-1 treatment
      of H441 cells. TSL-1 treatment-induced G(1) arrest was concurrent with the down
      regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441
      cells. Peroral and intraperitoneal administrations of TSL-1 were performed to
      evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also
      used to elucidate the therapeutic efficacy in the H441 cell xenograft model in
      vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both
      therapeutic and preventive experiments. Taken together, these results demonstrate
      that TSL-1 possesses the capability of preventing and alleviating lung cancer
      proliferation in vitro and in vivo with proven nephrological and hepatic safety
      and has the potential to be developed as an anti-lung cancer drug.

PMID- 20136437
TI  - Comparative chemical composition and antiproliferative activity of aerial parts
      of Salvia leriifolia Benth. and Salvia acetabulosa L. essential oils against
      human tumor cell in vitro models.
AB  - The aim of this work was to examine the chemical composition and
      antiproliferative activity of Salvia leriifolia Benth. and Salvia acetabulosa L.
      oils. S. leriifolia oil was characterized by 50 components, whereas 19 components
      were identified in S. acetabulosa. S. leriifolia oil was characterized by camphor
      (10.5%), 1,8-cineole (8.6%), camphene (6.2%), and alpha-pinene (4.7%). alpha
      Pinene (52.3%), 1,8-cineole (27.7%), and camphor (6.7%) were the major components
      in S. acetabulosa oil. Both oils exerted a strong antiproliferative activity
      comparing with vinblastine against COR-L23 with 50% inhibitory concentration
      (IC(50)) values of 7.5 and 6.5 microg/mL for S. leriifolia and S. acetabulosa,
      respectively. Salvia oils showed an interesting activity also on C32 (IC(50) =
      6.3 and 9.1 microg/mL for S. acetabulosa and S. leriifolia, respectively). S.
      acetabulosa was also found to possess cytotoxic activity against renal
      adenocarcinoma (IC(50) = 6.8 microg/mL). The results clearly showed that for both
      Salvia species the antiproliferative activity could not be related to the major
      abundant compounds. Consequently, the minor components may be involved in some
      type of synergism with the other active compounds.

PMID- 20136438
TI  - Dietary zinc and prostate cancer in the TRAMP mouse model.
AB  - Circumstantial evidence indicates that zinc may have an important role in the
      prostate. Total zinc levels in the prostate are 10 times higher than in other
      soft tissues. Zinc concentrations in prostate epithethial cancer cells are
      decreased significantly. Zinc supplementation for prevention and treatment of
      prostate cancer in humans has yielded controversial results. No studies have been
      reported in animal models to show the effect of zinc supplementation on
      prevention of prostate cancer, thus far. In this study, we have examined the
      effect of zinc supplementation on development of prostate cancer in a TRAMP mouse
      model. Results from our study indicate that dietary zinc plays an important role
      in prostate carcinogenesis. Tumor weights were significantly higher when the
      dietary zinc intake was either deficient or high in comparison to normal zinc
      intake level, suggesting that an optimal dietary zinc intake may play a
      protective role against prostate cancer. Further, our studies also showed
      decreased insulin-like growth factor (IGF)-1 and IGF-1/IGF binding protein-3
      ratio in normal zinc-supplemented animals, suggesting that zinc may modulate IGF
      1 metabolism in relation to carcinogenesis. We conclude that optimal prostate
      zinc concentration has a protective role against cancer.

PMID- 20136439
TI  - Dietary supplementation with pressurized whey in patients with cystic fibrosis.
AB  - Cystic fibrosis (CF) is characterized by malnutrition, chronic pulmonary
      inflammation, and oxidative stress. Whey protein is rich in sulfhydryl groups and
      is recognized for its ability to increase glutathione and reduce oxidative
      stress. Previously, we have shown that supplementation with whey increased
      intracellular glutathione levels in patients with CF. We have subsequently shown
      that hyperbaric pressure treatment of whey protein promotes the release of novel
      peptides for absorption, increases intracellular glutathione in healthy subjects,
      and reduces in vitro production of interleukin (IL)-8. We hypothesized that
      pressurized whey supplementation in children and adults with CF could have
      significant nutritional and anti-inflammatory benefits. A pilot open-label study
      of 1-month dietary supplementation with pressurized whey in CF patients was
      undertaken to assess the effects. Twenty-seven patients with CF (nine children,
      18 adults) were enrolled. The dose of pressurized whey was 20 g/day in patients
      less than 18 years of age and 40 g/day in older patients. Anthropometric
      measures, pulmonary function, serum C-reactive protein (CRP), whole blood
      glutathione, and whole blood IL-8 and IL-6 responses to phytohemagglutinin (PHA)
      stimulation were measured at baseline and at 1 month. Three adults withdrew (one
      with gastrointestinal side effects, two with acute infection). Both children and
      adults showed enhancements in nutritional status, as assessed by body mass index.
      Children showed improvement in lung function (forced expiratory volume in 1
      second). The majority of patients with an initially elevated CRP showed a
      decrease. PHA-stimulated IL-8 responses tended to decrease in the adults. Whole
      blood glutathione levels did not change. Thus, oral supplementation with
      pressurized whey improves nutritional status and can have additional beneficial
      effects on inflammation in patients with CF.

PMID- 20136440
TI  - Anti-ulcerogenic effect of a whey protein isolate and collagen hydrolysates
      against ethanol ulcerative lesions on oral administration to rats.
AB  - The effect of the administration of a whey protein isolate (WPI) and collagen
      hydrolysates on ethanol-induced ulcerative lesions was studied in rats. WPI and
      bovine or porcine collagen hydrolysate (BCH and PCH, respectively) were given to
      rats by gavage. In acute experiments, (single-dose) physiological saline (10
      mL/kg of body weight) was used as the negative control, and carbenoxolone (200
      mg/kg of body weight) was used as a positive control. Ethanol (1 mL per 250-g
      rat) was also given by gavage. These treatments reduced the ulcerative lesion
      index (ULI) in a range of 40-77%, depending on the dosage. Some mixtures of WPI
      with either PCH or BCH provided results that suggested synergisms between WPI and
      the collagen hydrolysates. For example, WPI/BCH (in the proportion of 375:375
      mg/kg of body weight) decreased ULI by 64%. The mechanism for mucosal protection
      involved a decrease in plasma gastrin (approximately 40%), a significant increase
      (50-267%) in mucus production, and a reduction in ULI (percentage) when
      intragastric administrations were performed after in vivo alkylation by N
      ethylmaleimide. Results suggest that gastrin, sulfhydryl substances, and some
      mechanisms related to mucus production are all involved in gastric ulcer
      protection against ethanol. The collagen hydrolysates (both PCH and BCH)
      presented a stronger effect on mucus production; on the other hand, the effect of
      WPI was also dependent on sulfhydryl compounds, resulting in a more protective
      effect when the two proteins were administered together.

PMID- 20136441
TI  - Ethanol and water extract of purple sweet potato exhibits anti-atherosclerotic
      activity and inhibits protein glycation.
AB  - It is well known that extracts of purple sweet potato (PSP) have potent
      antioxidant activity. However, it has not been established whether extracts of
      PSP inhibit oxidation of low-density lipoprotein (LDL) or protein glycation. LDL
      oxidation and protein glycation are well-known risk factors for chronic metabolic
      diseases, such as atherosclerosis and diabetes mellitus. Chopped and sliced PSP
      and yellow sweet potato (YSP) were extracted individually at a concentration of 1
      g of PSP tuber/mL using either ethanol or water for 6 hours. The PSP ethanol
      extract (100-fold diluted) showed stronger radical (2,2-diphenyl-1-picrylhydrazyl
      radical) scavenging activity than the water extract of PSP and the ethanol
      extract of YSP (up to a sixfold higher activity). The ethanol extract of PSP also
      exhibited the highest increase in ferric reducing ability among all extracts.
      Cupric ion-mediated LDL oxidation was strongly inhibited by the ethanol extract
      of PSP, with similar potency to vitamin C treatment (final concentration, 10 mM).
      The PSP extract strongly inhibited fructose-mediated protein glycation as
      determined by fluorescence spectroscopy. The PSP extract-treated apolipoprotein
      (apo) A-I showed a decreased multimerization pattern on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, whereas glycated apoA-I showed the strongest
      multimeric band. PSP extract treatment also inhibited the uptake of oxidized LDL
      into human macrophage cells with suppression of malondialdehyde production in the
      cell culture medium. In conclusion, these results suggest that the extract of PSP
      can be used as a putative anti-atherosclerotic and antidiabetic agent with strong
      antioxidant functions. This is the first report to show the biological functions
      of PSP extract to treat hyperlipidemic and hyperglycemic disorders.

PMID- 20136442
TI  - Monoacylglycerol (MAG)-oleic acid has stronger antioxidant, anti-atherosclerotic,
      and protein glycation inhibitory activities than MAG-palmitic acid.
AB  - A functional oil containing diacylglycerol (DAG) and monoacylglycerol (MAG) has
      been shown to have a strong anti-atherosclerotic effect in a mouse model. Among
      the lipid components, MAG is responsible for the beneficial effect with an
      enhanced antioxidant effect in the mouse model. In this report, several MAG
      containing fatty acids (MAG-oleic acid [MAG-O], MAG-palmitic acid [MAG-P], and
      MAG-stearic acid [MAG-S]) were synthesized, and the antioxidant and anti
      atherogenic activities were evaluated in vitro and in a cellular model. MAG-O had
      the strongest radical scavenging and antioxidant activities against copper
      mediated low-density lipoprotein (LDL) oxidation and the strongest inhibitory
      activity against LDL-associated phospholipase A(2) and exhibited potent
      activation of paraoxonase activity, which contributes to the maintenance of
      antioxidant activity. All MAG species in this study exhibited inhibitory activity
      against glycation of apolipoproteins, in contrast to DAG. Oxidized LDL uptake
      into THP-1 cells was strongly inhibited by MAG-O treatment at a final
      concentration of 20 microM. MAG-O-treated cell culture medium showed the lowest
      production of malondialdehyde and lipid hydroperoxide compared to MAG-S and MAG
      P. In conclusion, MAG-O had potent antioxidant, antidiabetic, and anti
      atherogenic effects in vitro and in a cellular model.

PMID- 20136443
TI  - Effects of a flavonol-rich diet on select cardiovascular parameters in a Golden
      Syrian hamster model.
AB  - The concept that the consumption of a diet rich in flavonoids can be associated
      with a reduced risk for cardiovascular disease is becoming increasingly accepted.
      In the present study we investigated the effects of the following four diets on
      blood pressure and cholesterol ester levels in hypercholesterolemic Golden Syrian
      hamsters: a high-fat, high-cholesterol diet (HFHC); a HFHC with 2% cranberry
      concentrate powder (HFHC+CE); a HFHC with 0.1% rutin (HFHC+Rutin); and a HFHC
      with 30 mg/kg vitamin E (HFHC+Vit.E). Diets were fed for either 12 or 20 weeks.
      Over the experimental period, heart rate and blood pressure measurements
      increased in the animals fed HFHC and HFHC+Vit.E; in contrast, these measurements
      were not increased in the animals fed HFHC+CE and HFHC+Rutin. Mesenteric and
      total abdominal fat were significantly lower in the animals fed HFHC+Rutin than
      in animals fed the other three diets. Ratios of plasma high-density lipoprotein
      cholesterol (HDL-C) to very-low-density lipoprotein cholesterol and of plasma HDL
      C to low-density lipoprotein cholesterol were significantly higher in animals
      consuming HFHC+Vit.E than in animals fed the other three diets. Aortic
      cholesteryl ester levels were significantly lower in animals fed HFHC+CE,
      HFHC+Rutin, and HFHC+Vit.E at 20 weeks than in the animals fed HFHC. Fasting
      blood glucose concentrations were significantly lower in animals fed HFHC+Rutin
      and HFHC+Vit.E, and glucose clearance rates improved in animals fed HFHC+Rutin
      compared to animals fed the other three diets. Results obtained from this study
      support the concept that the chronic consumption of a flavonoid-rich diet can be
      beneficial with respect to cardiovascular health.

PMID- 20136444
TI  - Strawberry consumption is associated with increased antioxidant capacity in
      serum.
AB  - Strawberries are known to contain antioxidants, but the significance of ingesting
      antioxidant-rich fruits remains to be established. In order to determine whether
      the consumption of strawberries impacted measures of in vivo antioxidant
      capacity, frozen strawberries (250 g) were administered daily for 3 weeks to 21
      healthy female volunteers. Compliance was confirmed by quantitating pelargonidin
      glucuronide, urolithin A-glucuronide, and 2,5-dimethyl-4-hydroxy-3-[(2)H]furanone
      glucuronide in plasma and urine by liquid chromatography-mass spectrometry and
      antioxidant capacity in serum measured by the increase in lag phase of low
      density lipoprotein after copper sulfate exposure, DNA strand breaks in
      lymphocytes, and activity of phase II enzymes. Among these measures lipid
      peroxidation lag time increased by 20% (P < .01), whereas other measures did not
      change significantly. The potent antioxidant defenses in humans make
      determination of changes due to dietary ingestion in healthy individuals
      difficult. In summary, daily consumption of strawberries resulted in a modest but
      significant increase in antioxidant capacity in a healthy population.

PMID- 20136445
TI  - Effects of various polyphenolics on hydrogen peroxide-induced p53 activity in
      NIH3T3 cells.
AB  - A cell-based assay system was developed to evaluate the potential antioxidant and
      pro-oxidant effects of various dietary polyphenolic compounds based on the
      induction of p53 activity by hydrogen peroxide. A p53-luciferase reporter vector
      was stably transfected into NIH3T3 cells. Individual clones were isolated, and
      one clone (number 33) was selected that showed the highest induction levels with
      different generators of free radicals. Clone 33 was preincubated for 1 hour with
      0, 0.1, 1.0, 10, 50, and 100 microM genistein, resveratrol, naringenin,
      quercetin, epicatechin gallate, and epigallocatechin-3-gallate and then treated
      with 40 microM hydrogen peroxide or left untreated for 4 hours. Cell lysates were
      prepared and assayed for luciferase activity. Results show that the effects on
      p53 activity by the different polyphenolics varied depending on the compound and
      concentration. Quercetin and genistein reduced p53 activity at 1.0 microM,
      whereas the other four compounds did not attenuate p53 activity. With the
      exception of naringenin, the other compounds increased p53 at the higher (50
      microM or 100 microM) amounts, without added hydrogen peroxide, suggesting that
      these compounds can act as pro-oxidants or possibly stimulate p53 activity by
      another mechanism.

PMID- 20136446
TI  - Effects of extracts of selected medicinal plants upon hepatic oxidative stress.
AB  - Aqueous extracts of a few medicinal plants traditionally used in Portugal have
      been assayed for their effects upon hepatic oxidative stress in mice. Previous in
      vitro studies had allowed characterization of agrimony, sage, savory, and
      raspberry in terms of overall antioxidant capacity and phenolic content. In the
      present study, the antioxidant effect and safety of these four plants were
      evaluated in vivo. For this purpose, mice ingested extracts in aqueous form (or
      water, used as the control) for 4 weeks; damage to lipids, proteins, and DNA was
      evaluated by oxidative cell biomarkers by the end of that period. Levels of
      hepatic glutathione and activities of enzymes involved in metabolism thereof were
      also determined. Finally, catalase and superoxide dismutase (SOD) activities were
      quantified, as these enzymes play a crucial role in antioxidant defense. When
      compared with the control, both raspberry and savory produced significant lipid
      protection; however, protein damage was significantly lower only in raspberry
      treated animals. On the other hand, DNA damage was prevented only by savory. All
      plants led to a decrease in catalase activity, whereas all but sage also produced
      a decrease in SOD activity. With regard to glutathione levels and activities of
      enzymes involved in its metabolism, the aforementioned extracts exhibited
      different effects. In general, raspberry appeared to be the most promising
      extract, followed by savory, sage, and agrimony, sorted by decreasing performance
      in protection; the latter was even slightly toxic. Hence, the plants tested
      possess compounds with interesting biological activities that may support
      eventual inclusion in food or feed as functional additives.

PMID- 20136447
TI  - Protective effect of Pimpinella anisoides ethanolic extract and its constituents
      on oxidative damage and its inhibition of nitric oxide in lipopolysaccharide
      stimulated RAW 264.7 macrophages.
AB  - The present study shows for the first time the chemical profile and the in vitro
      properties (antioxidant and inhibition of nitric oxide [NO] production) of the
      aromatic plant Pimpinella anisoides V Brig. (Family Apiaceae). The ethanolic
      extract of the fruits is characterized by 23 major components. Fourteen
      monoterpenes, two sesquiterpenes, one fatty acid, five methyl esters and one
      aldehyde were identified. Among them the most abundant components were the
      monoterpenes trans-anethole (54.5%), limonene (13.5%), and sabinene (4.4%). The
      extract showed significant antioxidant activity (50% inhibitory concentration
      [IC(50)], 3.02 mg/mL) using the 2,2-diphenyl-1-picrylhydrazyl test. The test for
      inhibition of NO production was performed using the murine monocytic macrophage
      cell line RAW 264.7. The ethanolic extract had significant activity with an
      IC(50) value of 72.7 microg/mL, and this might indicate that it would have an
      anti-inflammatory effect in vivo. Among the pure compounds that most effectively
      inhibited lipopolysaccharide-induced NO production were the most abundant
      constituents, trans-anethole and limonene, with IC(50) values of 102.7 microg/mL
      and 70.1 microg/mL, respectively. The cytotoxic effect of P. anisoides extract
      and pure compounds in the presence of lipopolysaccharide (1 microg/mL) was
      evaluated but found to be negligible.

PMID- 20136448
TI  - Medicinal mushroom Ganoderma lucidum (Leyss: Fr) Karst. triggers immunomodulatory
      effects and reduces nitric oxide synthesis in mice.
AB  - This study investigated the effect of Ganoderma lucidum supplementation on
      lymphocytes and peritoneal macrophages from mice. Our results show that G.
      lucidum in vivo was able to increase interferon-gamma (IFN-gamma) concentration
      but reduced CD3(+) and CD8(+) spleen lymphocytes. Ex vivo, IFN-gamma; and
      interleukin-10 levels were increased and the tumor necrosis factor-alpha (TNF
      alpha) level was reduced by peritoneal macrophages from mice fed with G. lucidum.
      In the absence of stimuli nitric oxide production was reduced in mice fed with G.
      lucidum, and with lipopolysaccharide stimulation nitric oxide production was
      increased but was lower than control values (P < .05). G. lucidum was grown by
      solid-state culture in wheat grain, and a chow containing 10% G. lucidum mycelium
      was formulated (G10). Swiss male mice were divided into two groups, termed G10
      and control groups according to the diet, and were fed for 3 months. Peritoneal
      macrophages were obtained and investigated with regard to phagocytosis, lysosomal
      volume, hydrogen peroxide, superoxide anion, and cytokines ex vivo. In the plasma
      we investigated concentrations of cytokines, and in the spleen we determined
      subsets of CD3(+), CD4(+), CD8(+), and CD19(+) lymphocytes.

PMID- 20136449
TI  - Influence of potent antioxidant leguminosae family plant extracts on growth and
      antioxidant defense system of Hep2 cancer cell line.
AB  - Legumes are considered to be a very good source of polyphenolic compounds that
      may act as chemopreventive agents, especially by their antioxidant properties.
      However, many of the chemopreventive properties may depend on the concentrations
      of the phytochemical compounds because potent antioxidant polyphenolic compounds
      may have pro-oxidant properties and negatively affect cell growth and viability.
      Thus, the aim of the present study was to assess the possible effect of two
      potent antioxidant Greek Leguminosae family plant extracts on the growth of a
      specific cancer cell line and its antioxidant defense cell system. Aqueous
      extracts of aerial parts of Lathyrus laxiflorus and Phaseolus vulgaris plants
      were initially examined for their cytotoxicity on the Hep2 cancer cell line at
      concentrations that possess potent antioxidant properties (100, 400, and 800
      microg/mL). After a 24-hour incubation with the extracts, only L. laxiflorus
      plant extract exhibited the ability to inhibit the cell growth at 400 and 800
      microg/mL by 57% and 74%, respectively, whereas P. vulgaris extract had no effect
      on cell growth at any of the tested concentrations. Noncytotoxic concentrations,
      100 microg/mL L. laxiflorus and 800 microg/mL P. vulgaris extract, were used for
      2-, 12-, and 24-hour incubation of the cells. The influence of the extracts on
      the antioxidant defense system of the cells was assessed by measuring the total
      antioxidant capacity (TAC) of the cells, the catalase (CAT) activity, and the
      concentrations of reduced glutathione, the oxidized form of glutathione, and
      thiobarbituric-reactive substances (TBARS) in all times of incubation with the
      cells. From the results obtained, it seems that only L. laxiflorus extract
      induces oxidative stress in the cells by reducing TAC and CAT activity and by
      inducing TBARS, especially with 2 and 12 hours of incubation. P. vulgaris extract
      reduced only TAC at 2 hours of incubation, indicating also a mild induction of
      oxidative stress. These results imply that potent antioxidant extracts, beyond a
      critical concentration, may induce oxidative stress even with no apparent
      cytotoxicity in cells.

PMID- 20136450
TI  - Anti-inflammatory properties of red ginger (Zingiber officinale var. Rubra)
      extract and suppression of nitric oxide production by its constituents.
AB  - Red ginger (Zingiber officinale var. Rubra) has been prescribed as an analgesic
      for arthritis pain in Indonesian traditional medicine. The surface color of the
      rhizome is purple because of the anthocyanidins in its peel. We prepared 40%
      ethanolic extract from dried red ginger (red ginger extract [RGE]) and evaluated
      its anti-inflammatory activity using acute and chronic inflammation models. In an
      acetic acid-induced mouse writhing model, RGE (10-100 mg/kg) suppressed both the
      frequency of writhing and the increase in permeability of abdominal capillaries.
      On the other hand, continuous treatment with RGE (10 mg/kg) significantly (P <
      .05) suppressed footpad edema in a rat adjuvant arthritis model. To clarify the
      anti-inflammatory mechanism of RGE, we examined the effect on prostaglandin (PG)
      and nitric oxide (NO) production from mouse leukemic monocytes (RAW264 cells)
      stimulated by lipopolysaccharide. RGE (3 and 10 microg/mL) significantly (P <
      .05) suppressed PGE(2) production, while it also suppressed NO production at 100
      microg/mL. After bioassay-guided separation of RGE, we found that [6]-shogaol and
      gingerdiols suppressed NO production. Red dye fractions presumed to be
      proanthocyanidins also suppressed NO production at 100 microg/mL. Consequently,
      we found a potent suppressive effect of RGE on acute and chronic inflammation,
      and inhibition of macrophage activation seems to be involved in this anti
      inflammatory effect. [6]-Shogaol, gingerdiols, and proanthocyanidins were
      identified as constituents that inhibited NO production.

PMID- 20136451
TI  - Inability of legumes to reverse diabetic-induced nephropathy in rats despite
      improvement in blood glucose and antioxidant status.
AB  - Diabetes mellitus has assumed epidemic proportions in most parts of the world,
      including developing countries, with vascular and renal complications being the
      major causes of death. Evidence is emerging that legumes play a beneficial role
      in diabetes and its associated complications. In connection with the above, four
      groups of alloxan-induced diabetic rats were fed on four different legume-based
      (Vigna unguiculata ssp. dekindtiana var. dekindtiana, V. unguiculata ssp.
      unguiculata, Sphenostylis stenocarpa, and Vigna subterranean) diets. Feeding rats
      with these diets for 5 weeks resulted in reduction of plasma glucose and changes
      in biomarkers of oxidative stress-namely, superoxide dismutase (SOD), peroxidase
      (PER), and thiobarbituric acid-reactive substances (TBARS). None of the legumes
      reversed the increase in plasma total protein associated with diabetes. The
      legumes increased PER activity and decreased the level of TBARS in the
      erythrocytes. A decrease in the activities of PER and SOD was observed in the
      kidneys of the diabetic rats. Nitric oxide (NO) production in the erythrocytes of
      the diabetic rats (as an index of diabetic endothelial dysfunction) increased for
      all the legumes in the following order: V. unguiculata ssp. unguiculata, V.
      unguiculata ssp. dekindtiana var. dekindtiana, V. subterranean, and S.
      stenocarpa. There was a significant increase (P < .05) in the uric acid
      concentration in the kidneys of treated rats. It is concluded that while the
      legumes have beneficial effects on reduction of hyperglycemia and strengthening
      the antioxidant status of the diabetic animals, the increased kidney uric acid
      concentration should be of concern.

PMID- 20136452
TI  - Neuroprotective activity of Vitis thunbergii var. taiwaniana extracts in vitro
      and in vivo.
AB  - Vitis thunbergii var. taiwaniana (VTT) is a wild grape native to Taiwan, where it
      has been used as a folk medicine. In this study, we found that the branch and
      leaf ethanol extracts of VTT significantly inhibited the inducible nitric oxide
      (NO) synthase protein expression and NO production in BV2 microglia. Using
      primary neuronal cells, kainic acid (KA) significantly increased hydrogen
      peroxide production in a dose-dependent manner. All four ethanol extracts of VTT
      significantly decreased hydrogen peroxide production. However, only root and
      branch ethanol extracts were able to prevent the neuronal cell death induced by
      KA in vitro. In the animal study, administration of all four plant part extracts
      of VTT delayed the onset of seizure and decreased the hippocampus neuronal cell
      loss, and the neuroprotective activity could be ranked as follows: branch
      approximately leaf > root > trunk. The results suggest that VTT extracts have a
      potential to prevent neurodegeneration through the antioxidative activity by
      their ability to inhibit NO and hydrogen peroxide production.

PMID- 20136453
TI  - Protective role of Ginkgo biloba against hepatotoxicity and nephrotoxicity in
      uranium-treated mice.
AB  - The aim of the present study was to investigate the protective role of Ginkgo
      biloba leaf extract against uranium (U)-induced toxicity in Swiss albino mice.
      The mice were randomly divided into six groups, each consisting of six animals:
      Group I (control) received tap water alone, Group II received U at a dose of 5
      mg/kg of body weight, Group III received G. biloba at a dose of 50 mg/kg of body
      weight, Group IV received G. biloba at a dose of 150 mg/kg of body weight, Group
      V received G. biloba (50 mg/kg of body weight) and U (5 mg/kg of body weight),
      and Group VI received G. biloba (150 mg/kg of body weight) and U (5 mg/kg of body
      weight) by oral gavage for 5 days. Serum aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels
      were determined to assess liver and kidney function, respectively. Also, liver
      and kidney samples were taken for the determination of tissue malondialdehyde
      (MDA) and reduced glutathione (GSH) levels, and histopathological changes in
      liver and kidneys were investigated. The results indicated that there was a
      significant increase (P < .05) in selected serum parameters. Serum AST, ALT, BUN,
      and creatinine levels significantly increased in mice treated with U alone when
      compared to the other groups. Moreover, U-induced oxidative damage caused a
      significant decrease in GSH levels and a significant increase in MDA levels of
      liver and kidney tissues. Treatment with G. biloba produced amelioration in
      biochemical indices of hepatotoxicity and nephrotoxicity according to Group II.
      Each dose of G. biloba provided significant protection against U-induced
      toxicity, and its strongest effect was observed at a dose of 150 mg/kg of body
      weight. In vivo results showed that G. biloba extract is a potent protector
      against U-induced toxicity, and its protective role is dose-dependent.

PMID- 20136454
TI  - Antibacterial and antifungal properties of acetonic extract of Feijoa sellowiana
      fruits and its effect on Helicobacter pylori growth.
AB  - Feijoa sellowiana Berg. fruit, widely used for human consumption, is well
      appreciated for its good nutritional characteristics and for its pleasant flavor
      and aroma. In a prior study we showed that the acetonic extract of F. sellowiana
      fruit exerts a potent antibacterial activity against some Gram-positive and Gram
      negative bacterial strains. To confirm and deepen the study on antimicrobial
      activities of the fruit, in this article we analyze the same extract for its
      effectiveness against different kind of bacteria both as American Type Culture
      Collection standard strains and clinically isolates, the Gram-negative
      Helicobacter pylori, and three fungal strains (one human pathogen and two
      phytopathogens). Our aim was also to isolate and define the active component(s)
      involved in the antibacterial, antifungal, and anti-H. pylori activity of the
      extract through activity-guided fractionation procedures. This allowed us to
      identify flavone as the active compound of F. sellowiana fruit. Flavone showed a
      high antibacterial activity against the nine standard bacterial strains tested
      and the matched clinically isolated bacterial strains and was significantly more
      active against H. pylori than metronidazole. Pseudomonas aeruginosa, Proteus
      mirabilis, and Proteus vulgaris from both standard and clinical sources showed a
      very high sensitivity to flavone (minimal inhibitory concentration [MIC] = 1.95
      microg/mL for standard strains and 3.9 microg/mL for clinical isolates of the
      three bacteria), showing also good minimal bactericidal concentration values.
      Among fungi tested, Rhyzoctonia solani was the most sensitive strain to the
      action of flavone (MIC = 62.5 microg/mL).

PMID- 20136455
TI  - Antimicrobial activities of essential oil and hexane extract of Florence fennel
      [Foeniculum vulgare var. azoricum (Mill.) Thell.] against foodborne
      microorganisms.
AB  - The objective of this study was to determine the chemical compositions of the
      essential oil and hexane extract isolated from the inflorescence, leaf stems, and
      aerial parts of Florence fennel and the antimicrobial activities of the essential
      oil, hexane extract, and their major component, anethole, against a large variety
      of foodborne microorganisms. Gas chromatography and gas chromatography-mass
      spectrometry analysis showed that the essential oils obtained from inflorescence,
      leaf stems, and whole aerial parts contained (E)-anethole (59.28-71.69%),
      limonene (8.30-10.73%), apiole (trace to 9.23%), beta-fenchyl acetate (3.02
      4.80%), and perillene (2.16-3.29%) as the main components. Likewise, the hexane
      extract of the plant sample exhibited a similar chemical composition, and it
      contained (E)-anethole (53.00%), limonene (27.16%), gamma-terpinene (4.09%), and
      perillene (3.78%). However, the hexane extract also contained less volatile
      components such as n-hexadecanoic acid (1.62%), methyl palmitate (1.17%), and
      linoleic acid (1.15%). The in vitro antimicrobial assays showed that the
      essential oil, anethole, and hexane extract were effective against most of the
      foodborne pathogenic, saprophytic, probiotic, and mycotoxigenic microorganisms
      tested. The results of the present study revealed that (E)-anethole, the main
      component of Florence fennel essential oil, is responsible for the antimicrobial
      activity and that the essential oils as well as the hexane extract can be used as
      a food preservative. This study is the first report showing the antimicrobial
      activities of essential oil and hexane extract of Florence fennel against
      probiotic bacteria.

PMID- 20136456
TI  - Immunomodulatory activity of type-4 resistant starch in the mesenteric lymph
      nodes of rats.
AB  - We evaluated the immunomodulatory activity of type-4 resistant starch (RS) in
      mesenteric lymph nodes (MLNs) using a rat model. Sixteen male Sprague-Dawley rats
      were fed either a cellulose diet or an RS diet (RSD) for 4 weeks. Serum
      immunoglobulin A levels, as well as the CD4(+) T cell population and the ratio of
      CD4(+)/CD8(+) T cells in the MLNs of rats, were significantly elevated by
      replacing cellulose with RS in the diet. The survival rate of concanavalin A (Con
      A)-stimulated MLN lymphocytes and interleukin-4 secretion from the Con A
      stimulated MLN lymphocytes were significantly increased in rats fed RSD. These
      results indicate that type-4 RS might ameliorate allergic inflammation in the
      MLNs of rats through an increased CD4(+) T cell population and enhanced
      differentiation of MLN lymphocytes into type-2 T cells.

PMID- 20136457
TI  - Antifatigue effect of coenzyme Q10 in mice.
AB  - The aim of this study was to investigate whether coenzyme Q10 (CoQ10) has an
      antifatigue effect in mice. ICR male mice were orally given CoQ10 in the form of
      Bio-Quinone (Pharma Nord, Vejle, Denmark) at doses of 0, 1.5, 15, or 45 mg/kg/day
      for 4 weeks. Mice were made to perform swimming exercise with loads attached to
      their tails, corresponding to approximately 5% of their body weights, and the
      total swimming time until exhaustion was measured. Furthermore, the post-exercise
      concentration of serum urea nitrogen (SUN), pre-/post-exercise and post-rest
      concentration of lactic acid (LA), and pre-exercise hepatic glycogen were
      determined. Mice treated with CoQ10 showed a significantly prolonged exhaustive
      swim time (15 mg/kg/day; P < .05), increased liver glycogen contents (15 and 45
      mg/kg/day; P < .01 and P < .05, respectively), and decreased SUN levels (1.5, 15,
      and 45 mg/kg/day; P < .01) compared to control animals. The LA level was not
      significantly changed. These results suggest that CoQ10 improves swimming
      endurance and has an antifatigue effect.

PMID- 20136458
TI  - Effects of coenzyme Q10 supplementation on plasma adiponectin, interleukin-6, and
      tumor necrosis factor-alpha levels in men.
AB  - The aim of the study was to determine the effects of coenzyme Q10 supplementation
      on plasma adiponectin, interleukin (IL)-6, and tumor necrosis factor (TNF )-alpha
      levels in sedentary men. Fourteen healthy, nonsmoking, sedentary men participated
      in the study. The protocol was approved by the Ethical Committee of our
      institution. This study was a randomized, double-blind, crossover trial. Blood
      samples were collected from all participants before coenzyme Q10 or placebo
      supplementation. The participants were randomly allocated to two groups. Seven
      participants received oral coenzyme Q10 (100 mg/day) supplementation, and seven
      participants received placebo (glucose) for 8 weeks. At the end of the 8 weeks, a
      second blood sampling was performed. After a 4-week washout period, placebo was
      given to the participants who used coenzyme Q10 the first time, and vice versa,
      and blood sampling was repeated. Plasma was stored at -80 degrees C until the
      time of analysis for adiponectin, IL-6, and TNF-alpha. Both CoQ10 and placebo
      supplementation did not affect plasma adiponectin and TNF-alpha levels. IL-6
      level increased with coenzyme Q10 supplementation, but this increase did not
      differ from that seen with placebo supplementation. Coenzyme Q10 supplementation
      did not affect plasma adiponectin, IL-6, and TNF-alpha levels in sedentary men.

PMID- 20136459
TI  - Antidepressant-like activity of Sonchus oleraceus in mouse models of immobility
      tests.
AB  - The aim of the present work is to evaluate the putative antidepressant-like
      effects of hydroethanolic and dichloromethanic extracts from the aerial parts of
      Sonchus oleraceus (Family Asteraceae) on the performance of male mice in the
      forced swimming test (FST) and tail suspension test (TST) models predictive of
      depression. The hydroethanolic and dichloromethanic extracts, both in doses of
      30, 100, and 300 mg/kg, were orally administered 1 hour before carrying out the
      FST or the TST. The immobility time in both the FST and the TST was significantly
      reduced by acute oral treatment with the extracts (dose range, 100-300 mg/kg),
      without accompanying changes in ambulation, as assessed in an open-field test.
      This excluded the possibility that the effect of the extracts is due to an
      activation of locomotion. The efficacy of the extracts was found to be comparable
      to that of amitriptyline (10 mg/kg, p.o.). The present study provides evidence
      for an antidepressant-like effect of the active principle(s) present in the
      extracts of S. oleraceus in mice. Therefore, a standardized S. oleraceus extract
      or its purified constituents could be of potential interest for the treatment of
      depressive disorders.

PMID- 20136460
TI  - Oxygen radical absorbance capacity of phycocyanin and phycocyanobilin from the
      food supplement Aphanizomenon flos-aquae.
AB  - The oxygen radical absorbance capacity (ORAC) assay has been widely used to
      quantify peroxyl radical scavenging capacity of pure antioxidant compounds and
      antioxidant plant/food extracts. However, it has never been applied to natural
      compounds derived from microalgae-based dietary supplements, namely, phycocyanin
      (PC) and phycocyanobilin (PCB), for which a strong radical scavenger activity has
      been documented. In this article, we applied the ORAC method to investigate the
      capacity of PC and PCB purified from the edible microalga Aphanizomenon flos
      aquae to directly quench peroxyl radicals in comparison to well-known
      antioxidants molecules such as Trolox, ascorbic acid, and reduced glutathione. As
      a result, PCB was found to have the highest ORAC value (22.18 micromol of
      Trolox/micromol of compound), comparable to that of PC (20.33 micromol of
      Trolox/micromol of compound), hence confirming that PCB is mostly responsible for
      the scavenger activity of PC and making the protein a possible source of the
      antioxidant in vivo. Our data further corroborate the use of these natural
      compounds from A. flos-aquae as dietary antioxidant supplements in the treatment
      of clinical conditions related to oxidative stress.

PMID- 20136461
TI  - Chemical composition and inhibitory activity against Helicobacter pylori of the
      essential oil of Apium nodiflorum (Apiaceae).
AB  - The chemical composition of the essential oil obtained from Apium nodiflorum (L.)
      Lag. (Family Apiaceae), a plant used in the ethnomedical traditions of the
      Abruzzo region (Central Italy) as a culinary herb, as a diuretic, and to cure
      stomachache, was analyzed by gas chromatography/mass spectrometry, and 14
      components were identified. Limonene (27.72 %), p-cymene (23.06%), myristicine
      (18.51%), and beta-pinene (6.62%) were the main components. The antimicrobial
      activity of the essential oil was assayed in vitro against Helicobacter pylori
      (strain DSMZ 4867), resulting in a minimum inhibitory concentration value of 12.5
      microg/mL.

PMID- 20136463
TI  - Roles of dextrans on improving lymphatic drainage for liposomal drug delivery
      system.
AB  - Our aim was to develop a novel liposomal drug delivery system containing dextrans
      to reduce undesirable retention of antineoplastic agents and thus alleviate local
      tissue damage. At the cell level, diethylaminoethyl-dextran (DEAE-Dx) showed the
      strongest inhibiting effect on liposome uptake by macrophages among tested
      dextrans. The distribution of radiolabeled liposomes mixed with dextrans in
      injection site and draining lymph node was investigated in rats after
      subcutaneous injection. DEAE-Dx substantially reduced the undesired local
      retention and promoted the draining of liposome into lymphatics, which was
      further confirmed by confocal microscopy images revealing the substantial
      prevention of rhodamine B-labelled liposome sequestration by macrophages in
      normal lymph node in rats. Pharmacokinetic data indicated the accelerated
      drainage of liposome through lymphatics back to systemic circulation by mixing
      with DEAE-Dx. In the toxicological study in rabbits, DEAE-Dx alleviated the local
      tissue damage caused by liposomal doxorubicin. In conclusion, dextrans,
      particularly DEAE-Dx, could efficiently enhanced liposomes drainage into
      lymphatics, which proves themselves as promising adjuvants for lymphatic-targeted
      liposomal drug delivery system.

PMID- 20136464
TI  - Neurolysis using a carbohydrate polymer gel for the treatment of postoperative
      neuropathic pain.
AB  - Perineural and intraneural fibrosis is thought to be the main cause of failure of
      the many surgical treatments of neuropathic pain. We have used Adcon-T/N
      carbohydrate polymer gel for prevention of perineural fibrosis in several parts
      of the body. In this retrospective study, 54 patients who presented with
      postoperative neuropathic pain had microsurgical epineural neurolysis and
      relocation of a terminal neuroma. In 19 of them, the carbohydrate gel was applied
      at the same time. The mean follow-up was four years and the nerve distribution
      varied. Postoperative improvement in pain scores (visual analogue scale (VAS) and
      neuropathic pain scale inventory (NPSI)), sensitivity, overall improvement and
      satisfaction were equivalent in the two groups, with pain relief in about 80% of
      the patients. There was no significant beneficial effect in the carbohydrate gel
      group. Patients treated with this device had a higher infection rate (21 compared
      with 0, p = 0.01) and delayed wound healing (31.6 compared with 11.8, p = 0.2).
      We conclude that good long-term pain relief is obtained postoperatively
      independently of the addition of carbohydrate gel. There was a slight but not
      significant trend towards profound pain relief with the gel.

PMID- 20136465
TI  - Healing of ununited scaphoid fractures by Kirschner wires and autologous
      structural bone grafts.
AB  - Untreated ununited scaphoid fractures are a hazard to the wrist because of
      increasing degenerative changes with time. We have treated 81 consecutive
      ununited scaphoid fractures by open reposition, autologous bone transplantation,
      and Kirschner wire fixation, 2.7 years after the primary injury. Sixty-nine were
      men and the mean age at operation was 29 (range 15-71) years. Anatomy of the
      wrist was restored and radiological healing confirmed in 72/81 patients. There
      were two deep infections, and the fractures did not heal. Patients with moderate
      preoperative arthritic wrist changes (scaphoid non-union advanced collapse (SNAC)
      stage 2) or ununited fractures of the proximal 1/6 of the scaphoid had worse
      healing than the remainder. Two of nine scaphoids that did not heal were
      reoperated on with autologous bone grafting and fixation with screws or pins,
      both of which healed successfully. Three salvage procedures (two wrist
      arthrodeses and one four corner fusion) were done and the remaining four declined
      further treatment. Our overall results are comparable to results published where
      alternative fixation methods have been used. We find that our standard method
      using Kirschner (K) wires and bone grafting is reliable and inexpensive for most
      scaphoid pseudarthroses and our results are comparable to published results when
      alternative fixation methods have been used.

PMID- 20136466
TI  - Effect of lip adhesion on maxillary arch alignment and reduction of a cleft's
      width before definitive cheilognathoplasty in unilateral and bilateral complete
      cleft lip.
AB  - High tension and tissue dislocation caused by wide maxillary clefts could prevent
      an optimal aesthetic and functional outcome in primary cheilognathoplasty. Many
      surgical techniques or conservative (orthodontic and orthopaedic) devices have
      been proposed for the initial management of infants with complete cleft lip and
      palate to achieve a tension-free repair of the lip. Adhesion converts a wide
      unilateral complete cleft into a lesser deformity anatomically similar to an
      incomplete cleft lip. This study aimed to measure the effect of lip adhesion on
      the width of maxillary clefts. Between 2000 and 2007 lip adhesion was used on 49
      consecutive infants affected by complete unilateral (n = 35) and bilateral (n =
      14) cleft lip and palate. The indication for lip adhesion was the presence of a
      wide alveolar cleft (gap > 7 mm) with severely malpositioned maxillary segments.
      Lip adhesion was done at about 48 days, followed by definitive cheilognathoplasty
      at 98 days. Photographs and impressions were obtained before any operation. The
      width of the maxillary clefts was reduced by 60% in unilateral clefts and 61% in
      bilateral clefts. By converting a complete wide cleft lip to an incomplete cleft
      in both unilateral and bilateral clefts, adhesion of the lip achieved a better
      position and stabilised the arch in a symmetrical platform that eased both
      definitive closure of the defect in the lip and the restoration of the maxillary
      gap by periosteoplasty during definitive cheilognathoplasty.

PMID- 20136467
TI  - Carpal tunnel syndrome and treatment of recurrent symptoms.
AB  - Carpal tunnel syndrome is the most common compression lesion of peripheral nerves
      with a prevalence of 4%. It is often treated by release of the flexor
      retinaculum, which may completely relieve the symptoms. Although such treatment
      is considered successful, there are probably many patients with persistent or
      recurrent symptoms. Recurrence implies that the patient's symptoms were initially
      relieved but recurred some time after the operation; this is a controversial
      field in which clear definitions, aetiology, diagnosis, and treatment seem
      uncertain. We describe recurrence of carpal tunnel syndrome and summarise
      possibilities for diagnosis and treatment of the condition.

PMID- 20136468
TI  - Infraeyebrow excision blepharoplasty for Japanese blepharochalasis: review of 35
      patients over 60 years old.
AB  - Since 2005 we have treated many older patients with upper blepharochalasis but no
      obvious aponeurotic ptosis by infraeyebrow excision of skin and orbicular muscle
      with tucking of the orbital septum. Thirty-five patients (70 lids) were studied,
      age range 61-80 years (mean 68). There were 6 men and 29 women, who were followed
      up for 3 months to 2 years (mean 7 months). All patients reported improvement in
      the upper visual fields and lessening of headaches and neck stiffness. The
      lateral drooping of the lid also improved, and the crease was more clearly
      defined than before the operation. There were no serious complications. We
      conclude that infraeyebrow blepharoplasty with tucking of the orbital septum is a
      simple and effective treatment for blepharochalasis in older East Asian patients.

PMID- 20136469
TI  - Gamiwalbitang, composed of four herbs, controls body weight increase and lipid
      level elevation induced by a high-fat diet in mice.
AB  - Gamiwalbitang (GWB) is a newly developed dietary supplement that is composed of
      four herbs. The purpose of GWB development is to help control weight. The aim of
      this study was to investigate whether GWB combined with a 40% high-fat (HF) diet
      can influence body weight and fat accumulation. An experiment was conducted with
      40 C57BL/6J mice with an initial body weight of approximately 18g. Body weight
      was recorded weekly, and plasma levels of triglyceride, low-density lipoprotein
      (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and leptin were
      analyzed at the end of the study. Weight increases in the 10% GWB group were
      38.5% less than in the HF diet group (P < 0.05). Plasma triglyceride and LDL
      cholesterol levels decreased by 21.2% and 51.0%, respectively, in the 5% GWB
      group, and 44.1% and 51.5%, respectively, in the 10% GWB group compared to the HF
      diet group. The HDL cholesterol level was increased by 184.0% in the 5% GWB group
      and 188.2% in the 10% GWB group. The serum leptin level was significantly
      decreased by the GWB diet, and in the GWB diet group; gene expression of leptin
      in adipose tissue was also decreased compared with HF diet group. These findings
      indicate that GWB may be beneficial in the regulation of high-fat diet-induced
      blood circulatory disorders.

PMID- 20136470
TI  - A prospective study of cognitive behavioural factors as predictors of pain,
      disability and quality of life one year after lumbar disc surgery.
AB  - PURPOSE: The primary aim of this study was to analyse the predictive value of
      cognitive and behavioural factors, in relation to pain, disability and quality of
      life (QoL) one year after lumbar disc surgery. METHOD: The study design was
      prospective. Fifty-nine patients scheduled for first time lumbar disc surgery
      were included. Pain, disability, QoL, coping, fear avoidance beliefs, expected
      outcome and sick leave were assessed preoperatively and 12 months after surgery.
      Multiple backward stepwise logistic regression analyses were performed to study
      the contribution of the preoperatively measured independent behavioural/cognitive
      factors (coping, fear avoidance beliefs and assessed chance to return to work
      within 3 months) to the dependent variables pain, disability and quality of life
      at 12 months after surgery. RESULTS: Low expectations on work return within 3
      months after surgery was significantly predictive for residual leg pain, odds
      ratio (OR) = 8.2, back pain, OR = 9.7, disability, OR = 13.8 and sick leave, OR =
      19.5. Low QoL, was best predicted by preoperatively high scores on fear avoidance
      beliefs OR = 6.6 and being a woman OR = 6.0. The regression model explained 26
      40% of the variance in pain, disability, QoL and sick leave. CONCLUSIONS:
      Eliciting patients' expectations on work return after surgery could contribute to
      early identification of those who run the risk of developing long-term disability
      and sick-leave.

PMID- 20136471
TI  - Evaluation of single event multilevel surgery and rehabilitation in children and
      youth with cerebral palsy--A 2-year follow-up study.
AB  - PURPOSE: This study evaluated multilevel surgery and rehabilitation with
      functional measures and health related quality of life (HRQOL) of children and
      youth with cerebral palsy (CP). In addition this study evaluated parent's
      satisfaction with care. METHOD: A prospective single-subject study with AB design
      and 2-year follow-up, included 11 children between 8 and 18 years old with CP,
      Gross Motor Function Classification System I-III. Visual analyses were used to
      present physical function with Physical Cost Index (PCI). Descriptive statistics
      were used to present number of children with a clinically important change in
      Gross Motor Function Measure (GMFM), self-reported walking ability, and HRQOL
      with child health questionnaire (CHQ). RESULTS: PCI showed a trend of lower
      energy cost during gait in six children and GMFM was unchanged for 10 children
      and improved for one child. Walking ability was improved in 10 children. Gait
      distance increased in all 11. Both physical and psychosocial dimensions of CHQ
      improved in six of nine (two missing data). Expectations of outcomes were
      fulfilled in seven and partly fulfilled in four. Satisfaction with care was
      fulfilled in 10 of 11. CONCLUSION: Self-reported walking ability improved after
      multilevel surgery and intensive rehabilitation. This result was partly supported
      by lower energy cost and improved HRQOL. Expectations and satisfaction were
      fulfilled for the majority of children.

PMID- 20136472
TI  - 'There's a real plan here, and I am responsible for that plan': participant
      experiences with a novel cognitive-based treatment approach for adults living
      with chronic stroke.
AB  - PURPOSE: This study was part of a larger mixed methods project aimed at adapting
      the Cognitive Orientation to daily Occupational Performance (CO-OP) treatment
      approach, originally designed for children with performance problems, for use
      with adults with stroke. In CO-OP, the client focuses on learning strategies and
      skills, rather than on remediating impairments. Therapists use guided discovery
      to teach cognitive strategy use. The purpose of this study was to explore
      participants' experiences with the approach. METHOD: Semistructured interviews
      were conducted with five participants. Transcriptions were coded by two members
      of the research team. Data analysis was conducted in two distinct phases:
      Directed content analysis was conducted to apply codes to predetermined
      categories; Thematic analysis was conducted to allow themes grounded in the data
      to emerge. RESULTS: Participants reported learning and transferring the
      strategies taught, and made suggestions for modifications to the approach, such
      as increasing the number of sessions. One theme emerged, Balancing the need for
      autonomy with the need for support. CONCLUSIONS: The findings suggest the
      cognitive strategies were well learned and effectively used. CO-OP was able to
      provide participants with increased decision-making autonomy, but may require
      modifications to better support their transition to higher levels of
      independence.

PMID- 20136473
TI  - Functioning of stroke survivors--A validation of the ICF core set for stroke in
      Sweden.
AB  - PURPOSE: To validate the body functions and activities and participation part of
      the extended International Classification of Functioning, Disability, and Health
      (ICF) core set for stroke with a Swedish population in the first 3 months post
      stroke. METHOD: At 6 weeks and at 3 months post-stroke, stroke survivors were
      evaluated by 59 ICF categories of body functions, 59 categories of activities and
      participation from the stroke ICF core set (extended version). RESULTS: The study
      sample included 99 stroke survivors (54% women) with an average age of 72 years.
      Statistical significant problems were identified in 28 ICF categories of body
      functions and in 41 ICF categories of activities and participation at both time
      points, at 6 weeks and at 3 months. About 17 ICF categories were reported as
      problems in independent (i.e. modified Rankin Scale (mRS) < or =2) and about 34
      categories in dependent (i.e. mRS > 2) stroke survivors. CONCLUSIONS: The results
      suggest a possible reduction of the stroke ICF core set from 59 to 28 categories
      of body functions and from 59 to 41 categories of activities and participation.
      Hence, feasibility of the core set for multiprofessional assessment increases and
      the core set might find more integration in clinical practice. The number of
      problems in mobility and self-care mainly distinguished between independent and
      dependent stroke survivors.

PMID- 20136474
TI  - The effectiveness of functional electrical stimulation for the treatment of
      shoulder subluxation and shoulder pain in hemiplegic patients: A randomized
      controlled trial.
AB  - PURPOSE: To investigate the effect of functional electrical stimulation (FES) for
      the treatment of shoulder subluxation and shoulder pain in hemiplegic patients.
      METHOD: A total of 50 hemiplegic patients with shoulder subluxation and shoulder
      pain were included in the study. The patients were randomly divided into the
      study and control groups. All patients were put on a rehabilitation program using
      conventional methods while the study group patients were additionally applied FES
      to supraspinatus and posterior deltoid muscles. The shoulder pain of all patients
      during resting, passive range of motion (PROM) and active range of motion (AROM)
      was measured with the visual analog scale (VAS) while the shoulder subluxation
      levels were evaluated with the classification developed by Van Langenberghe and
      by using the millimetric measurements on anteroposterior shoulder X-ray before
      and after the physical treatment and rehabilitation program and compared.
      RESULTS: Comparison of the resting AROM vs. PROM VAS value changes showed no
      significant difference between the groups. There was a significant difference
      between the two groups for the amount of change in shoulder subluxation in favor
      of the study group. CONCLUSIONS: The results of our study have shown that
      applying FES treatment to the supraspinatus and posterior deltoid muscles in
      addition to conventional treatment when treating the subluxation in hemiplegic
      patients is more beneficial than conventional treatment by itself.

PMID- 20136475
TI  - Qualitative study of principles pertaining to lifestyle and pressure ulcer risk
      in adults with spinal cord injury.
AB  - PURPOSE: The aim of this article is to identify overarching principles that
      explain how daily lifestyle considerations affect pressure ulcer development as
      perceived by adults with spinal cord injury (SCI). METHOD: Qualitative in-depth
      interviews over an 18-month period with 20 adults with spinal injury and a
      history of pressure ulcers were conducted using narrative and thematic analyses.
      RESULTS: Eight complexly interrelated daily lifestyle principles that explain
      pressure ulcer development were identified: perpetual danger; change/disruption
      of routine; decay of prevention behaviors; lifestyle risk ratio;
      individualization; simultaneous presence of prevention awareness and motivation;
      lifestyle trade-off; and access to needed care, services and supports.
      CONCLUSIONS: Principles pertaining to the relationship between in-context
      lifestyle and pressure ulcer risk underscore previous quantitative findings, but
      also lead to new understandings of how risk unfolds in everyday life situations.
      Pressure ulcer prevention for community-dwelling adults with SCI can potentially
      be enhanced by incorporating principles, such as the decay of prevention
      behaviors or lifestyle trade-off, that highlight special patterns indicative of
      elevated risk. The identified principles can be used to theoretically drive
      future research or to guide innovative lifestyle-focused intervention approaches.
      Public policies that promote short-term preventive interventions at critical
      junctures throughout a person's life should be considered.

PMID- 20136476
TI  - A population-based study of demographical variables and ability to perform
      activities of daily living in adults with osteogenesis imperfecta.
AB  - PURPOSES: To describe demographical variables, and to study functional ability to
      perform activities of daily life in adults with osteogenesis imperfecta (OI).
      METHODS: Population-based study. Ninety-seven patients aged 25 years and older,
      41 men and 56 women, were included. For the demographical variables, comparison
      was made to a matched control-group (475 persons) from the Norwegian general
      population. Structured interviews concerning social conditions, employment and
      educational issues and clinical examination were performed. The Sunnaas
      Activities of Daily Living (ADL) Index was used to assess the ability to perform
      ADL. RESULTS: The prevalence of clinical manifestations according to Sillence was
      in accordance with other studies. Demographical variables showed that most adults
      with OI are married and have children. They had a higher educational level than
      the control group, but the employment rate was significantly lower. However, the
      rate of employed men was similar in both groups. Adult persons with OI achieved a
      high score when tested for ADL. CONCLUSIONS: Adults with OI are well educated
      compared with the general population, and most of them are employed. High scores
      when tested for ADL indicate that most of them are able to live their lives
      independently, even though there are some differences according to the severity
      of the disorder.

PMID- 20136477
TI  - Effect and process evaluation of implementing standardized tests to monitor
      patients in spinal cord injury rehabilitation.
AB  - PURPOSE: To evaluate the implementation of standardized physical and functional
      tests to monitor patients with a spinal cord injury (SCI) in eight rehabilitation
      centers and to analyze the enablers and the barriers of the implementation
      process. METHOD: The method involved prospective effect and process evaluation.
      Team members responded to mailed questionnaires at the start (n = 115) and end (n
      = 82) of the 1-year implementation period. Furthermore, a questionnaire was
      administered to managers (n = 8), coordinators (n = 8), and 32 persons with SCI
      in four centers. Outcome of the effect evaluation was the phase of implementation
      of standardized testing in each center. The process evaluation analyzed enablers
      and barriers of the implementation process. RESULTS: After a year of
      implementation, half of the centers shifted to higher implementation phases. None
      of the centers was classified in the highest phase. Enablers were the positive
      attitude of the team members regarding standardized testing and an encouraging
      local coordinator. Most important barrier was lack of time to implement the
      standardized testing. CONCLUSION: There is a large support for implementing
      standardized tests to monitor patients with SCI. During the 1-year, a positive
      shift was visible in the extent of implementation. Successful implementation of
      patient monitoring requires substantial amounts of time and effort of the
      rehabilitation centers involved.

PMID- 20136478
TI  - Paracetamol (acetaminophen) attenuates in vitro mast cell and peripheral blood
      mononucleocyte cell histamine release induced by N-acetylcysteine.
AB  - INTRODUCTION: The treatment of acute paracetamol (acetaminophen) poisoning with N
      acetylcysteine (NAC) is frequently complicated by an anaphylactoid reaction to
      the antidote. The mechanism that underlies this reaction is unclear. We used the
      human mast cell line 1 (HMC-1) and human peripheral blood mononucleocytes (PBMCs)
      to investigate the effects of NAC and paracetamol on histamine secretion in
      vitro. METHOD: HMC-1 and human PBMCs were incubated in the presence of increasing
      concentrations of NAC +/- paracetamol. Cell viability was determined by the
      Trypan Blue Assay, and histamine secretion was measured by ELISA. RESULTS: NAC
      was toxic to HMC-1 cells at 100 mg/mL and to PBMCs at 67 mg/mL. NAC increased HMC
      1 and PBMC histamine secretion at concentrations of NAC from 20 to 50 mg/mL and
      2.5 to 100 mg/mL, respectively. NAC-induced histamine secretion by both cell
      types was reduced by co-incubation with 2.5 mg/mL of paracetamol. CONCLUSION:
      Paracetamol (acetaminophen) is capable of modifying histamine secretion in vitro.
      This may explain the clinical observation of a lower incidence of adverse
      reactions to NAC in vivo when higher concentrations of paracetamol are present
      than when paracetamol concentrations are low. Paracetamol (acetaminophen)
      attenuates in vitro mast cell and PBMC cell histamine release induced by NAC.

PMID- 20136479
TI  - Guanfacine overdose resulting in initial hypertension and subsequent delayed,
      persistent orthostatic hypotension.
AB  - INTRODUCTION: Guanfacine is an alpha(2)-adrenoreceptor agonist used for the
      treatment of attention-deficit hyperactivity disorder and tic disorders. Few
      reports exist regarding overdose with guanfacine. CASE REPORT: A 16-year-old
      female with Tourette's syndrome presented with diaphoresis, dry mouth, and
      hypertension 8 h after ingesting 25 mg of guanfacine. These symptoms improved and
      her blood pressure (BP) normalized over 2 h. Thirty hours following ingestion,
      she experienced near syncope and returned to the emergency department. She was
      noted to have orthostatic hypotension and a prolonged QTc interval of 593 ms on
      electrocardiogram. With only fluid support, she was asymptomatic by 60 h
      postingestion and her QTc interval had improved to 511 ms. DISCUSSION: This
      experience suggests a much delayed onset of symptoms may occur and that the QTc
      interval may be prolonged, necessitating a longer period of monitoring in a
      patient presenting with an overdose.

PMID- 20136480
TI  - Mass intoxication with Datura innoxia--case series and confirmation by analytical
      toxicology.
AB  - BACKGROUND: Anticholinergic plants contain a variety of alkaloids that are toxic
      if ingested. Datura innoxia belongs to the family of Solanaceae and contains two
      main toxic alkaloids, atropine and scopolamine. CASE SERIES: In this study we
      report the case series of seven individuals who were admitted to two different
      hospitals of Athens with an anticholinergic syndrome. All symptoms manifested
      after consumption of cooked vegetables (blites). INVESTIGATION: The investigation
      of the cases revealed that among the vegetables there was also Datura innoxia,
      which has a similar appearance to blites. Urine and plasma samples of the seven
      patients, as well as a sample of cooked vegetables, were analyzed with gas
      chromatography-mass spectrometry. Atropine and scopolamine were confirmed in all
      urine and vegetable samples, but not in plasma probably because of the delay in
      sample collection. The urine samples of all patients contained atropine in
      concentrations between 67.1 and 691.7 ng/mL, while urine concentrations of
      scopolamine ranged from 32.4 to 186.4 ng/mL. The concentrations of atropine and
      scopolamine in the cooked vegetables were found to be 0.8 and 1.2 microg/g,
      respectively. CONCLUSION: All patients recovered completely, although some
      required mechanical ventilation. The investigation and the presentation of this
      case series illustrate not only mass intoxication with D. innoxia, but also the
      utility of analytical toxicology. It also illustrates the dangers of collection
      of vegetables in the wild.

PMID- 20136481
TI  - A prospective observational study of the clinical toxicology of glyphosate
      containing herbicides in adults with acute self-poisoning.
AB  - CONTEXT: The case fatality from acute poisoning with glyphosate-containing
      herbicides is approximately 7.7% from the available studies but these have major
      limitations. Large prospective studies of patients with self-poisoning from known
      formulations who present to primary or secondary hospitals are needed to better
      describe the outcome from acute poisoning with glyphosate-containing herbicides.
      Furthermore, the clinical utility of the glyphosate plasma concentration for
      predicting clinical outcomes and guiding treatment has not been determined.
      OBJECTIVE: To describe the clinical outcomes, dose-response, and glyphosate
      kinetics following self-poisoning with glyphosate-containing herbicides. METHODS:
      This prospective observational case series was conducted in two hospitals in Sri
      Lanka between 2002 and 2007. We included patients with a history of acute
      poisoning. Clinical observations were recorded until discharge or death. During a
      specified time period, we collected admission (n = 216, including five deaths)
      and serial (n = 26) blood samples in patients. Severity of poisoning was graded
      using simple clinical criteria. RESULTS: Six hundred one patients were
      identified; the majority ingested a concentrated formulation (36%, w/v
      glyphosate). Twenty-seven percent were asymptomatic, 63.7% had minor poisoning,
      and 5.5% of patients had moderate to severe poisoning. There were 19 deaths (case
      fatality 3.2%) with a median time to death of 20 h. Gastrointestinal symptoms,
      respiratory distress, hypotension, altered level of consciousness, and oliguria
      were observed in fatal cases. Death was strongly associated with greater age,
      larger ingestions, and high plasma glyphosate concentrations on admission (>734
      microg/mL). The apparent elimination half-life of glyphosate was 3.1 h (95% CI =
      2.7-3.6 h). CONCLUSIONS: Despite treatment in rural hospitals with limited
      resources, the mortality was 3.2%, which is lower than that reported in previous
      case series. More research is required to define the mechanism of toxicity,
      better predict the small group at risk of death, and find effective treatments.

PMID- 20136482
TI  - Massive ingestion of cardiac drugs: toxicokinetic aspects of digoxin and sotalol
      during hemofiltration.
AB  - CASE: We present the case of a 75-year-old patient admitted to the emergency
      department after ingesting a large amount of several cardiac drugs, among which
      were digoxin and sotalol. Because of renal insufficiency, cardiogenic shock, and
      high serum digoxin levels, the patient received continuous venovenous
      hemofiltration (CVVH) and digoxin-specific Fab fragments. Digoxin and the digoxin
      specific Fab fragments are normally cleared by the kidneys. METHODS: Serum-free
      and total digoxin and serum sotalol concentrations were monitored for several
      days. RESULTS: Less than 10% of the estimated ingested dose of digoxin was
      cleared by CVVH within 5 days. CONCLUSION: CVVH has little influence on the
      clearance of Fab-bound digoxin from the body. In contrast, sotalol is efficiently
      cleared by CVVH.

PMID- 20136483
TI  - In vitro and in vivo evaluation of fenofibrate solid dispersion prepared by hot
      melt extrusion.
AB  - OBJECTIVE: This article aimed to develop fenofibrate solid dispersion with high
      bioavailability using hot-melt extrusion and compare the difference of Eudragit
      E100 and polyvinylpyrrolidone-vinyl acetate copolymer S630 (PVP-VA) in
      dissolution. METHODS: Solid dispersion with carrier of Eudragit E100 or PVP-VA
      was prepared by hot-melt extrusion and then characterized by differential
      scanning calorimetry (DSC), X-ray diffraction, in vitro dissolution test, and in
      vivo bioavailability study. RESULTS: Fenofibrate exited as noncrystal state in
      these two kinds of solid dispersions that can be proved by DSC and X-ray
      diffraction. Eudragit E100 1:2 solid dispersion has the dissolution of 84% and
      65% at 60 minutes in 0.1M HCl and water, respectively. Eudragit E100 1:4 solid
      dispersion has lower dissolution in 0.1M HCl and higher dissolution in water; the
      values are 73.6% and 87.3%. PVP-VA 1:2 solid dispersion has the dissolution of
      60% and 65% at 60 minutes in 0.1M HCl and water, respectively. PVP-VA 1:4 solid
      dispersion has higher dissolution in 0.1M HCl and lower dissolution in water; the
      values are 64% and 53%. The different dissolution of fenofibrate from the two
      polymers is because of their different solubility and gelling tendency. When
      Eudragit E100 1:4 solid dispersion was administrated to beagle dogs, its relative
      bioavailability to micronization Lipanthyl capsule was 177.1%. CONCLUSION: Hot
      melt extrusion is an excellent method to improve the dissolution and therefore
      the bioavailability of fenofibrate.

PMID- 20136484
TI  - The influence of chirality, physicochemical properties, and permeation enhancers
      on the transdermal permeation of amlodipine across rat skin.
AB  - PURPOSE: This study was aimed at investigating the possible relationship between
      the physical properties and the permeation of S-amlodipine and RS-amlodipine and
      studying the possible enantioselectivity of permeation of amlodipine in the
      presence and absence of enhancers, such as terpene enhancers and ethanol. METHOD:
      The solubility of S-amlodipine and RS-amlodipine was measured using the shake
      flask method. The thermodynamic properties were investigated by differential
      scanning calorimetry (DSC). The type of racemate amlodipine was investigated by
      DSC and Fourier transform infrared spectroscopy (FTIR). The permeability of
      racemate and enantiomers of amlodipine through rat epidermis in vitro was
      investigated using the modified Franz diffusion cell. RESULTS: The aqueous
      solubility of S-amlodipine was higher than that of RS-amlodipine. The melting
      temperature and enthalpy of fusion of S-amlodipine were lower than those of RS
      amlodipine. RS-amlodipine was a racemic compound. The permeation of the
      enantiomers of amlodipine from RS-amlodipine reservoir showed no significant
      differences in the presence and absence of enhancers, but the permeation of S
      amlodipine from S-amlodipine reservoir was significantly higher than that of RS
      amlodipine from RS-amlodipine reservoir 30% ethanol, 50% ethanol, and terpene
      enhancers could not influence the difference in permeation between S-amlodipine
      and RS-amlodipine, but 75% ethanol could reduce the difference. CONCLUSION: These
      results suggested that there was no enantioselectivity of the enantiomers of
      amlodipine from RS-amlodipine reservoir in the presence and absence of enhancers,
      but the differences in physical properties between S-amlodipine and RS-amlodipine
      led to the difference in permeation across rat skins.

PMID- 20136485
TI  - Targeted drug delivery of Rifampicin to the lungs: formulation, characterization,
      and stability studies of preformed aerosolized liposome and in situ formed
      aerosolized liposome.
AB  - PURPOSE: This study aimed at the preparation and characterization of preformed
      and in situ formed liposomes for sustained delivery to the lungs. METHODS: Two
      different liposome formulations were prepared and subjected to characterization
      of physical parameters and drug release profile (% cumulative drug release and %
      drug retained). Formulations were then subjected to accelerated stability studies
      as per ICH guidelines. RESULTS: In situ formed liposome showed better sustained
      release profile than the preformed liposome as it released sufficient amount of
      drug while retaining considerable amount of drug. Upon subjection to accelerated
      conditions for 60 days, preformed liposome lost the objective of being controlled
      release formulation.

PMID- 20136486
TI  - Positively and negatively charged liposomes as carriers for transdermal delivery
      of sumatriptan: in vitro characterization.
AB  - BACKGROUND: The influence of liposome composition, lamellarity, preparation
      method, and charge on the encapsulation efficiency, size, polydispersity, and
      surface charge of sumatriptan liposomes was studied. For this purpose, we studied
      multilamellar, unilamellar, and frozen and thawed liposomes. Positively or
      negatively charged liposomes were obtained using both phosphatidylcholine and
      cholesterol, in combination with stearylamine or dicetylphosphate. Liposomal
      formulations were characterized by confocal laser scanning microscopy and optical
      microscopy for vesicle formation, morphology, and lamellarity by dynamic laser
      light scattering for size distribution and polydispersity, and electrophoretic
      mobility for zeta potential determination. To obtain more information about the
      sumatriptan encapsulation, dynamic dialysis technique was employed. The
      sumatriptan amount was quantified by high-performance liquid chromatography.
      RESULTS: Overall obtained results showed that liposomes may be interesting
      carriers for sumatriptan succinate. Statistical analysis evidenced that the
      preparation method does not affect the evaluated characterization parameters.
      However, the presence of charge inducer agents modified these characteristics.
      Highest loading efficiency of sumatriptan was exhibited for positively charged
      liposomes containing 6.58:10.34:3.73 mmolar ratio for phosphatidylcholine :
      cholesterol : stearylamine. The mean size was affected by the charge inducer,
      being smaller in positively charged liposomes. Logically, surface charge of
      liposomes varied as a function of the employed charged agent. Also, interesting
      results were obtained when vesicles were loaded with sumatriptan, showing a
      statistical significance between all pairs, comparing the formulations with and
      without drug. CONCLUSION: Results obtained revealed that the presence of
      sumatriptan into the vesicles has a different behavior in negatively and
      positively charged liposomes.

PMID- 20136487
TI  - Computational prediction of local drug effect on carcinogenic acetaldehyde in the
      mouth based on in vitro/in vivo results of freely soluble L-cysteine.
AB  - BACKGROUND: The computational models for predicting oral drug absorption in
      humans using in vitro and in vivo data have been published. However, only a
      limited number of studies are available on the prediction of local drug efficacy
      in the mouth using computational models. AIM: The goal of this study was to
      develop a simulation model for prediction of drug amount and effect on
      carcinogenic acetaldehyde in the mouth. METHODS: The model was based partly on
      our previous studies in which we showed in vivo that l-cysteine-containing
      tablets can eliminate carcinogenic salivary acetaldehyde in the mouth during
      smoking. To develop as informative a model as possible, we also investigated
      whether a lower saliva pH (4.7) can affect the freely soluble l-cysteine
      dissolution rate and cysteine stability profile in the mouth, compared to the
      normal saliva pH of 7.4. RESULTS: Stability of the active drug is not pH
      dependent and thus users with normal, healthy saliva pH and those with lower pH
      can benefit from cysteine-containing products. The simulated saliva profiles of l
      cysteine and acetaldehyde corresponded to the in vivo results. CONCLUSIONS: The
      model developed can be used as an alternative tool to obtain faster and cheaper
      answers on how freely soluble drugs affect local conditions in the mouth. Because
      tobacco smoke contains more than 60 carcinogenic compounds, the model developed
      can offer a new view in eliminating or reducing not only one toxic compound from
      smoke but also many others compounds using only one formulation containing
      various active compounds.

PMID- 20136488
TI  - Assessment of intestinal absorption of total flavones of Hippophae rhamnoides L.
      in rat using in situ absorption models.
AB  - PURPOSE: The objective of this study was to investigate the absorption behavior
      of total flavones of Hippophae rhamnoides L. (TFH) (the sum of isorhamnetin and
      quercetin as the index component) in the rat intestine using in situ circulation
      method. METHODS: The accumulated TFH absorption and related absorption parameters
      were calculated. Furthermore, the influences of Cremophor ELP and the P
      glycoprotein inhibitor, verapamil, on the intestinal absorption of TFH were
      studied using the in situ circulation model. RESULTS AND DISCUSSION: The results
      showed that the absorption of TFH increased linearly with its concentration,
      indicating that a passive diffusion process was dominated. There were no
      significant differences in the absorption of TFH in three small intestine
      segments of duodenum, jejunum, and ileum and at different concentrations of
      Cremophor ELP ranging from 0.25% to 1% (P > 0.05). With the presence of P-gp
      inhibitor, verapamil, in the circulation fluid, the accumulated absorption of TFH
      did not increase significantly (P > 0.05). Further studies on the solubility and
      permeability enhancement of TFH should be investigated to develop new TFH
      products with high bioavailability.

PMID- 20136489
TI  - Development of a high-throughput UHPLC-MS-based content uniformity method as a
      tool for assessing dry powder inhalers.
AB  - BACKGROUND: Dry powder inhaler (DPI) product manufacturing requires the
      assessment of uniformity at various stages of the manufacturing process. RESULTS:
      To efficiently and precisely determine the uniformity of the small doses inherent
      to DPI technology, an ultrahigh-performance liquid chromatography-mass
      spectrometry (UHPLC-MS)-based content uniformity method was developed. Using
      mathematical modeling and proper selection of bracketing standards, a volumetric
      approximation of sample weight was utilized, eliminating the need for accurate
      sample weights and reducing sample preparation time. CONCLUSION: UHPLC-MS coupled
      with mathematical modeling makes high-throughput CU testing of DPI drug products
      possible which allows for an enhanced understanding of the manufacturing process.

PMID- 20136490
TI  - Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery: an
      alternative approach to oral and parenteral routes.
AB  - BACKGROUND: The aim of this study was to develop chitosan microspheres for nasal
      delivery of ondansetron hydrochloride (OND). METHOD: Microspheres were prepared
      with spray-drying method using glutaraldehyde as the crosslinking agent.
      Microspheres were characterized in terms of morphology, particle size, zeta
      potential, production yield, drug content, encapsulation efficiency, and in vitro
      drug release. RESULTS: All microspheres were spherical in shape with smooth
      surface and positively charged. Microspheres had also high encapsulation
      efficiency and the suitable particle size for nasal administration. In vitro
      studies indicated that all crosslinked microspheres had a significant burst
      effect, and sustained drug release pattern was observed until 24 hours following
      burst drug release. Nasal absorption of OND from crosslinked chitosan
      microspheres was evaluated in rats, and pharmacokinetic parameters of OND
      calculated from nasal microsphere administration were compared with those of both
      nasal and parenteral administration of aqueous solutions of OND. In vivo data
      also supported that OND-loaded microspheres were also able to attain a sustained
      plasma profile and significantly larger area under the curve values with respect
      to nasal aqueous solution of OND. CONCLUSION: Based on in vitro and in vivo data,
      it could be concluded that crosslinked chitosan microspheres are considered as a
      nasal delivery system of OND.

PMID- 20136491
TI  - Indomethacin-5-fluorouracil-methyl ester dry emulsion: a potential oral delivery
      system for 5-fluorouracil.
AB  - OBJECTIVE: To produce a combined effect of indomethacin (IDM) and 5-fluorouracil
      (5FU) for cancer therapy, the side effects of IDM on the gastrointestinal (GI)
      tract were reduced and the oral adsorption of 5FU was improved. Indomethacin-5
      fluorouracil-methyl ester (IFM) dry emulsion was prepared and evaluated as a
      potential oral delivery system for 5FU. METHODS: IFM was synthesized by formation
      of an ester between IDM and 5FU intermediate and then characterized by structure,
      melting point, solubility, apparent partition coefficient, and incubation with GI
      tract contents and plasma. Gum acacia and sodium carboxymethyl cellulose (CMC-Na)
      were applied as the adsorbent and solid carrier to prepare IFM dry emulsion. IFM
      dry emulsion was then characterized by reconstitution in water and in situ
      intestinal perfusion experiment. RESULTS: Physicochemical properties of the new
      synthesized compound confirmed the formation of IFM. Incubation of IFM in the
      contents of the GI tract and plasma revealed that IFM was not relatively stable
      in GI contents during the time period of transit through the GI tract, whereas it
      was very unstable in plasma and released 5FU rapidly. The IFM dry emulsion could
      be easily reconstituted in water, and the mean particle size was 2.416 microm.
      The absorption rate constant (K) for IFM with concentration of 2, 5, and 10
      microg/mL in the in situ perfusion experiment were 0.473, 0.423, and 0.433/h,
      respectively, demonstrating passive diffusion of IFM across the biological
      membranes. CONCLUSION: This study indicates that the IFM dry emulsion may
      represent a potentially useful oral delivery system for 5FU.

PMID- 20136492
TI  - High-amylose sodium carboxymethyl starch matrices for oral, sustained drug
      release: development of a spray-drying manufacturing process.
AB  - CONTEXT: High-amylose sodium carboxymethyl starch (HASCA) was recently proposed
      as a material for oral, sustained drug-release tablets prepared by direct
      compression. It was produced on a pilot scale, but appeared to be unsuitable for
      tableting and sustained drug release. Pilot-scale dry powder HASCA was dispersed
      in hot water and then precipitated with ethanol to give a dry powder presenting
      the required properties, but very high volumes of ethanol were used to recover
      the product. OBJECTIVE: A process was therefore designed to transform totally
      amorphous pregelatinized HASCA by spray-drying into a suitable sustained drug
      release excipient for matrix tablets while decreasing ethanol quantities. RESULTS
      AND DISCUSSION: During the first manufacturing step, that is, heating of the
      initial hydro-alcoholic suspension, powder and water concentrations are key
      parameters for the acquisition of excellent binding properties. Hence, a variable
      ratio of amylose Vh, a crystalline polymorph of amylose, to the amorphous form,
      is observed depending on the key parameter values. As the most crystalline
      samples give the weakest tablets, binding properties do not appear to be linked
      to the presence of a Vh form of amylose. On the other hand, a high water
      concentration results in excessive tablet strength, that is, inverse conditions
      leading to the appearance of a Vh form of amylose. Finally, variations in hydro
      alcoholic composition appear to affect only tableting properties and do not
      influence the drug-release rate. CONCLUSION: A process designed to transform
      totally amorphous pregelatinized HASCA by spray-drying is proposed for easier,
      economical industrial HASCA production.

PMID- 20136493
TI  - In vitro and in vivo evaluation of self-microemulsifying drug delivery system of
      buparvaquone.
AB  - AIM: The aim of this study was to prepare a lipid-based self-microemulsifying
      drug delivery system (SMEDDS) to increase the solubility and oral bioavailability
      of a poorly water-soluble compound, buparvaquone (BPQ). METHODS: The solubility
      of BPQ was determined in various vehicles, and pseudo-ternary phase diagrams were
      constructed to determine the microemulsion region. A series of formulations with
      different compositions were selected in the microemulsion region for assessment
      of self-emulsification time and droplet size. The optimized SMEDDS formulation
      was used for in vitro dissolution and pharmacokinetic studies in rabbits.
      RESULTS: The optimum formulation of SMEDDS consisted of Capryol 90 (9.82%),
      Cremophor EL (70.72%), Labrasol (17.68%), and BPQ (1.78%). Emulsification time
      and the mean droplet size were found to be 1 minute and 18.0 +/- 0.25 nm,
      respectively, for the optimum formulation. The cumulative percentage of drug
      released in 90 minutes was 100% in both SGF and SIF. The calculated absolute oral
      bioavailability for BPQ was found to be 40.10%. CONCLUSIONS: The optimum SMEDDS
      formulation was increased the rate and extent of absorption of BPQ. The
      formulation is suitable for oral administration of BPQ. It would be useful to
      conduct efficacy studies of BPQ in diseased animal models and subsequently for
      toxicokinetics studies.

PMID- 20136494
TI  - Influence of histidine on the release of all-trans retinoic acid from self
      assembled glycol chitosan nanoparticles.
AB  - OBJECTIVE: In this study, the influence of N-acetyl histidine (NAHis) on the all
      trans retinoic acid (ATRA) release from the NAHis-conjugated self-assembled
      glycol chitosan (GC) nanoparticles was investigated. METHODS: NAHis was
      conjugated to GC as a hydrophobic moiety to prepare the self-assembled
      nanoparticles, and ATRA was incorporated into the inner core of the NAHis-GC
      nanoparticles. The ATRA release from NAHis-GC nanoparticles was performed at 37
      degrees C in a phosphate-buffered saline buffer (pH 5.5 or 7.4) for 48 hours.
      RESULTS: At a pH of 5.5, less than 20% (w/w) of total loading amount of ATRA was
      released from the nanoparticles after 48 hours. In contrast, two times greater
      amount of ATRA was released at a pH of 7.4. The ATRA release rate from the NAHis
      GC nanoparticles was significantly slower at a pH of 5.5 than at a pH of 7.4.
      CONCLUSION: The release profiles of ATRA that was incorporated into the NAHis-GC
      nanoparticles were controlled by the NAHis content in the GC nanoparticles.

PMID- 20136495
TI  - Characterization and formulation optimization of solid lipid nanoparticles in
      vitamin K1 delivery.
AB  - BACKGROUND: Solid lipid nanoparticle (SLN) systems have been applied to various
      drugs and delivery routes. Vitamin K1 is an important cofactor for maintaining
      hemostasis and preventing hemorrhage. METHOD: Vitamin K1-loaded SLNs are
      systematically being developed by optimizing triglycerides and lipophilic and
      hydrophilic surfactants based on the size and stability of the resulting SLNs.
      Concentrations of the surfactants, Myverol and Pluronic, were optimized by a
      central composite design and response surface methodology. Vitamin K1
      (phylloquinone) was used as a lipophilic drug in the SLN system to evaluate the
      potential for oral delivery. RESULTS: Vitamin K1-loaded SLNs had a mean size of
      125 nm and a zeta potential of -23 mV as measured by photon correlation
      spectroscopy. The prepared SLNs were examined by differential scanning
      calorimetry and transmission electron microscopy and found to have an imperfect
      crystalline lattice and a spherical morphology. Effects of ultrasonication
      duration and drug load on the particle size and entrapment efficiency of the SLNs
      were also evaluated. CONCLUSION: More than 85% of the vitamin K1 was entrapped in
      SLNs when the payload was <5%. The vitamin K1 in SLNs was stable for a 54-h
      duration in simulated gastric and intestinal fluids. The particle size and
      vitamin K1 entrapped in the SLN were stable after 4 months of storage at 25
      degrees C. The results demonstrated that SLNs prepared herein can potentially be
      exploited as carriers for the oral delivery of vitamin K1.

PMID- 20136496
TI  - Preparation and characterization of nanostructured lipid carriers loaded
      traditional Chinese medicine, zedoary turmeric oil.
AB  - BACKGROUND: The objective of this work was to study the preparation and
      characteristics of zedoary turmeric oil (ZTO), a traditional Chinese oily
      medicine, loaded with nanostructured lipid carriers (NLCs). METHOD: Aqueous
      dispersions of NLC were successfully prepared by melt-emulsification technique
      using Crodamol SS as the solid lipid, Miglyol 812N as the liquid oil, and soybean
      phosphatidylcholine (SbPC) as the emulsifier. Properties of NLC such as the
      particle size and its distribution, the transmission electron microscope (TEM),
      drug entrapment efficiency (EE), and drug release behavior were investigated,
      respectively. The Germacrone blood concentration after intravenous administration
      of ZTO-NLC was determined and compared with that of ZTO-injection. RESULT: As a
      result, the drug EEs were improved by adding the liquid lipid into the solid
      lipid of nanoparticles (SLNs). In vitro drug release experiments indicated that
      the prepared NLC could enhance the drug release rate over the SLN, and the drug
      release rate could be adjusted by the liquid lipid content in lipid nanospheres.
      X-ray and differential scanning calorimetry (DSC) measurements revealed that
      imperfect crystallization occurred in the inner core of the NLC particles.
      CONCLUSION: The results suggest that the presented NLC system might be a
      promising intravenous dosage form of water-insoluble oily drugs.

PMID- 20136497
TI  - Synthesis of a novel polymer bile salts-(polyethylene glycol)2000-bile salts and
      its application to the liver-selective targeting of liposomal DDB.
AB  - PURPOSE: The objective of this study was to achieve a sustained and targeted
      delivery of liposome to the liver, by modifying the phospholipid
      [phosphatidylcholine (PC)/cholesterol (10 : 1) liposomes with a novel polymer
      bile salts-(polyethylene glycol)(2000)-bile salts (BP(2)B). METHODS: First, we
      generated a novel BP(2)B by N,N'-dicyclohexylcarbodiimide/4-dimethylaminopyridine
      esterification method and confirmed by Fourier transform infraredand (1) H-NMR
      spectra. Second, we prepared the BP(2)B-modified liposomes (BP(2)BL) that
      included BP(2)B, and the effect of the weight ratios of BP(2)B/PC on entrapment
      efficiency was investigated and BP(2)B/PC = 3% (w/w) was determined as the
      optimum ratio for the 4,4'-dimethoxy-5,6,5',6'-bi (methylenedioxy)-2,2'
      bicarbomethoxybiphenyl liposomes. And then, the ability of the liver target of
      BP(2)BL was studied by calculating the targeted parameters. RESULTS AND
      DISCUSSION: All the results revealed that the introduction of polyoxyethylene
      chains could control interactions of bile salt moieties on liposome surfaces with
      the receptor compared with traditional liposomes (CL), marking BP(2)BL as a
      suitable carrier for hepatic parenchymal cell-specific and sustained targeting.
      It was suggested that liposomes containing such novel BP(2)B have great potential
      as drug delivery carriers for the liver-selective targeting that has targeted and
      sustained drug delivery.

PMID- 20136498
TI  - Aerodynamic indices of velopharyngeal function in childhood apraxia of speech.
AB  - Childhood apraxia of speech (CAS) is characterized as a deficit in the motor
      processes of speech for the volitional control of the articulators, including the
      velum. One of the many characteristics attributed to children with CAS is
      intermittent or inconsistent hypernasality. The purpose of this study was to
      document differences in velopharyngeal function in children diagnosed with CAS
      from children with typically-developing speech. Pressure-flow techniques were
      used to estimate the velopharyngeal port size and measure the temporal sequencing
      of airflow and pressure events associated with production of a nasal + oral
      plosive sequence in the speech of three children with CAS and three age-matched
      comparison participants. The results of this pilot study revealed significant
      differences between the performance of the CAS group and the comparison group in
      three timing measures of velopharyngeal port closure and velopharyngeal orifice
      area during speech.

PMID- 20136499
TI  - Redox control of protein kinase C: cell- and disease-specific aspects.
AB  - Hormones, growth factors, electrical stimulation, and cell-cell interactions
      regulate numerous cellular processes by altering the levels of second messengers,
      thus influencing biochemical reactions inside the cells. The Protein Kinase C
      family (PKCs) is a group of serine/threonine kinases that are dependent on
      calcium (Ca(2+)), diacylglycerol, and phospholipids. Signaling pathways that
      induce variations on the levels of PKC activators have been implicated in the
      regulation of diverse cellular functions and, in turn, PKCs are key regulators of
      a plethora of cellular processes, including proliferation, differentiation, and
      tumorigenesis. Importantly, PKCs contain regions, both in the N-terminal
      regulatory domain and in the C-terminal catalytic domain, that are susceptible to
      redox modifications. In several pathophysiological conditions when the balance
      between oxidants, antioxidants, and alkylants is compromised, cells undergo redox
      stress. PKCs are cell-signaling proteins that are particularly sensitive to redox
      stress because modification of their redox-sensitive regions interferes with
      their activity and, thus, with their biological effects. In this review, we
      summarize the involvement of PKCs in health and disease and the importance of
      redox signaling in the regulation of this family of kinases.

PMID- 20136500
TI  - TNF-alpha-induced mitochondrial alterations in human T cells requires FADD and
      caspase-8 activation but not RIP and caspase-3 activation.
AB  - Although much is known about how TNF-alpha induces apoptosis in the presence of
      inhibitors of protein synthesis, little is known about how it induces apoptosis
      without these inhibitors. In this report we investigated temporal sequence of
      events induced by TNF-alpha in the absence of protein synthesis. Regardless of
      whether we measured the effects by plasma membrane phosphotidylserine
      accumulation, by DNA strand breaks, or activation of caspases, significant
      changes were observed only between 12-24 h of TNF-alpha treatment. One of the
      earliest changes observed after TNF-alpha treatment was mitochondrial swelling at
      10 min; followed by cytochrome c and Smac release at 10-30 min, and then
      heterochromatin clumping occurred at 60 min. While genetic deletion of receptor
      interaction protein (RIP) had no effect on TNF-alpha-induced mitochondrial
      damage, deletion of Fas-associated death domain (FADD) abolished the TNF-induced
      mitochondrial swelling. Since pan-caspase inhibitor z-VAD-fmk abolished the TNF
      alpha-induced mitochondrial changes, z-DEVD-fmk, an inhibitor of caspase-3 had no
      effect, suggesting that TNF-alpha-induced mitochondrial changes or cytochrome c
      and Smac release requires caspase-8 but not caspase-3 activation. Overall, our
      results indicated that mitochondrial changes are early events in TNF-alpha
      induced apoptosis and that these mitochondrial changes require recruitment of
      FADD and caspase-8 activation, but not caspase-3 activation or RIP recruitment.

PMID- 20136501
TI  - FOXO4 induces human plasminogen activator inhibitor-1 gene expression via an
      indirect mechanism by modulating HIF-1alpha and CREB levels.
AB  - The plasminogen activator inhibitor-1 (PAI-1) expression can be enhanced by
      hypoxia and various stimuli associated with oxidative stress. Among the FOXO
      transcription factors, FOXO4 appears to be crucial in the response against
      oxidative stress. Therefore, it was the aim of this study to investigate the role
      of peroxide-induced oxidative stress and FOXO4 on PAI-1 expression under normoxia
      and hypoxia. Treatment of cells with hydrogen peroxide increased PAI-1 mRNA,
      protein, and promoter activity, and knocking down FOXO4 abolished the peroxide
      dependent PAI-1 induction. PAI-1 promoter reporter gene assays revealed that the
      peroxide and FOXO4-dependent induction was mediated through the HIF-1 and CREB
      binding HRE within the PAI-1 promoter. Western blot analyses then indicated that
      peroxide and FOXO4 downregulated HIF-1alpha levels, whereas CREB levels were
      increased. Chromatin immunoprecipitations showed that FOXO4 did not bind the PAI
      1 promoter, whereas CREB binding was enhanced on FOXO4 overexpression. In
      addition, knockdown of CREB abolished the FOXO4-mediated PAI-1 induction.
      Together, these findings provide the first evidence that oxidative stress and
      FOXO4 induce PAI-1 expression through an indirect mechanism involving modulation
      of HIF-1alpha and CREB protein levels and that enhanced CREB binding to the PAI-1
      promoter is critical for the PAI-1 induction under oxidative stress.

PMID- 20136502
TI  - Redox regulation of SCO protein function: controlling copper at a mitochondrial
      crossroad.
AB  - Reversible changes in the redox state of cysteine residues represent an important
      mechanism with which to regulate protein function. In mitochondria, such redox
      reactions modulate the localization or activity of a group of proteins, most of
      which function in poorly defined pathways with essential roles in copper delivery
      to cytochrome c oxidase (COX) during holoenzyme biogenesis. To date, a total of 8
      soluble (COX17, COX19, COX23, PET191, CMC1-4) and 3 integral membrane (COX11,
      SCO1, SCO2) accessory proteins with cysteine-containing domains that reside
      within the mitochondrial intermembrane space (IMS) have been identified in yeast,
      all of which have human orthologues. Compelling evidence from studies of COX17,
      SCO1, and SCO2 argues that regulation of the redox state of their cysteines is
      integral to their metallochaperone function. Redox also appears to be crucial to
      the regulation of a SCO-dependent, mitochondrial signaling pathway that modulates
      the rate of copper efflux from the cell. Here, I review our understanding of
      redox-dependent modulation of copper delivery to COX and IMS-localized copper
      zinc superoxide dismutase (SOD1) during the maturation of each enzyme, and
      discuss how this in turn may serve to functionally couple mitochondrial copper
      handling pathways with those localized elsewhere in the cell to regulate cellular
      copper homeostasis.

PMID- 20136503
TI  - Cytosolic disulfide bond formation in cells infected with large nucleocytoplasmic
      DNA viruses.
AB  - Proteins that have evolved to contain stabilizing disulfide bonds generally fold
      in a membrane-delimited compartment in the cell [i.e., the endoplasmic reticulum
      (ER) or the mitochondrial intermembrane space (IMS)]. These compartments contain
      sulfhydryl oxidase enzymes that catalyze the pairing and oxidation of cysteine
      residues. In contrast, most proteins in a healthy cytosol are maintained in
      reduced form through surveillance by NADPH-dependent reductases and the lack of
      sulfhydryl oxidases. Nevertheless, one of the core functionalities that unify the
      broad and diverse set of nucleocytoplasmic large DNA viruses (NCLDVs) is the
      ability to catalyze disulfide formation in the cytosol. The substrates of this
      activity are proteins that contribute to the assembly, structure, and infectivity
      of the virions. If the last common ancestor of NCLDVs was present during
      eukaryogenesis as has been proposed, it is interesting to speculate that viral
      disulfide bond formation pathways may have predated oxidative protein folding in
      intracellular organelles.

PMID- 20136504
TI  - Perception of American English dark /l/ by normally hearing young adult women.
AB  - This perceptual study describes changes in how listeners perceive VCV elements
      within successive truncations taken from an iambic phrase containing /l/ (e.g. a
      leaf, or a load) spoken by four male speakers of General American English.
      Evidence of the respective roles of dorsal gestural affiliation between /l/ and
      the reduced vowel, (V(1)CV(2)), and gestural separation from a tautosyllabic high
      front vowel (V(2)) were demonstrated. Coproduction of dark-l with a preceding
      reduced vowel was evident in early reports of back vowels or diphthongs,
      particularly when the carrier word contained a front vowel, and was noted more in
      darker-l than lighter-l speakers. The pairing of /l/ with a tautosyllabic front
      vowel reduced earlier identification of /l/, whereas its pairing with a back
      vowel enhanced early identification. The role of perceived contrast in
      identification of /l/ was reflected in changes in listener's perception of the
      reduced vowel across successive truncations. Clinical implications are addressed.

PMID- 20136505
TI  - Investigating the use of coherence analysis on mandibular electromyograms to
      investigate neural control of early oromandibular behaviours: A pilot study.
AB  - An empirical method for investigating differences in neural control of jaw
      movement across oromandibular behaviours is to compute the coherence function for
      electromyographic signals obtained from mandibular muscle groups. This procedure
      has been used with adults but not extended to children. This pilot study
      investigated if coherence analysis could reveal task-related differences in
      control for children by measuring mandibular electromyograms obtained from an
      infant and adult. Electromyographic signals were obtained from bilateral masseter
      and temporalis muscle groups during chewing and babble from a typically
      developing infant from 8-22 months, and chewing and speech were obtained from an
      adult. Coherence functions were computed. Measures obtained from the infant and
      adult exhibited a significant main effect for task, with peak coherence values
      within 20-60 Hz being significantly greater for chewing than vocalization. This
      pilot study suggests that coherence analysis of mandibular EMG is a sensitive
      measure for distinguishing task-related differences in neural organization for
      children.

PMID- 20136506
TI  - Transcribing nonsense words: The effect of numbers of voices and repetitions.
AB  - Transcription skills are crucially important to all phoneticians, and
      particularly for speech and language therapists who may use transcriptions to
      make decisions about diagnosis and intervention. Whilst interest in factors
      affecting transcription accuracy is increasing, there are still a number of
      issues that are yet to be investigated. The present paper considers how the
      number of voices and the number of repetitions affects the transcription of
      nonsense words. Thirty-two students in their second year of study for a BSc in
      Speech and Language Therapy were participants in an experiment. They heard two
      nonsense words presented 10 times in either one or two voices. Results show that
      the number of voices did not affect accuracy, but that accuracy increased between
      six and ten repetitions. The reasons behind these findings, and implications for
      teaching and learning, and further research are discussed.

PMID- 20136507
TI  - Phonological processes in Kannada-speaking adolescents with Down syndrome.
AB  - Phonological process analysis was carried out using a 40-word imitation task with
      30 11;6-14;6 year old Kannada-speaking persons with Down syndrome in comparison
      with 15 non-verbal mental age matched typically developing children. Percentages
      of occurrence were significantly higher for the Down syndrome group with certain
      exceptions. Some phonological processes were observed only in the Down syndrome
      group. Kannada is a non-Indo European language spoken in the southern Indian
      state of Karnataka that has not had much research attention, especially with
      respect to persons with communication disorders. This paper highlights the
      phonological processes observed in school-aged persons with Down syndrome, some
      of which are similar to those observed in English and Dutch (cluster reduction,
      stopping, gliding, consonant harmony) and others that differ owing to differences
      in Kannada's phonology (e.g. retroflex fronting, degemination). The study gives a
      cross-linguistic perspective to the study of phonological processes in Down
      syndrome.

PMID- 20136508
TI  - Angiotensin II type 1 receptor-dependent oxidative stress mediates endothelial
      dysfunction in type 2 diabetic mice.
AB  - The mechanisms underlying the effect of the renin-angiotensin-aldosterone system
      (RAAS) inhibition on endothelial dysfunction in type 2 diabetes are incompletely
      understood. This study explored a causal relationship between RAAS activation and
      oxidative stress involved in diabetes-associated endothelial dysfunction. Daily
      oral administration of valsartan or enalapril at 10 mg/kg/day to db/db mice for 6
      weeks reversed the blunted acetylcholine-induced endothelium-dependent
      dilatations, suppressed the upregulated expression of angiotensin II type 1
      receptor (AT(1)R) and NAD(P)H oxidase subunits (p22(phox) and p47(phox)), and
      reduced reactive oxygen species (ROS) production. Acute exposure to AT(1)R
      blocker losartan restored the impaired endothelium-dependent dilatations in
      aortas of db/db mice and also in renal arteries of diabetic patients (fasting
      plasma glucose level > or =7.0 mmol/l). Similar observations were also made with
      apocynin, diphenyliodonium, or tempol treatment in db/db mouse aortas. DHE
      fluorescence revealed an overproduction of ROS in db/db aortas which was
      sensitive to inhibition by losartan or ROS scavengers. Losartan also prevented
      the impairment of endothelium-dependent dilatations under hyperglycemic
      conditions that were accompanied by high ROS production. The present study has
      identified an initiative role of AT(1)R activation in mediating endothelial
      dysfunction of arteries from db/db mice and diabetic patients.

PMID- 20136509
TI  - A novel mechanism, uniquely dependent on mitochondrial calcium accumulation,
      whereby peroxynitrite promotes formation of superoxide/hydrogen peroxide and the
      ensuing strand scission of genomic DNA.
AB  - High concentrations of peroxynitrite elicit delayed formation of DNA-damaging
      species through a mechanism dependent on mitochondrial Ca(2+) accumulation and
      inhibition of complex III. A second mechanism, requiring remarkably lower
      peroxynitrite concentrations, is observed in the presence of bona fide complex
      III inhibitors and is Ca(2+) independent. We now report evidence for a third
      mechanism, also operative with low peroxynitrite concentrations, independent of
      electron transport, and entirely based on mitochondrial Ca(2+) accumulation. This
      concept was established by using permeabilized respiration-proficient and 
      deficient U937 cells supplemented with Ca(2+), inhibitors of mitochondrial Ca(2+)
      accumulation, and specific respiratory-chain inhibitors. The results obtained
      were validated by experiments performed with intact cells, by using caffeine (Cf
      ) to promote mitochondrial Ca(2+) accumulation. Under these conditions, low
      concentrations of peroxynitrite, otherwise unable to generate detectable DNA
      cleavage, caused maximal DNA strand scission through a mechanism insensitive to
      respiratory-chain inhibitors or to the respiration-deficient phenotype. The
      effects of Cf were mimicked by other ryanodine receptor agonists, were suppressed
      by ryanodine, and were not observed in cells failing to express the ryanodine
      receptor, as differentiated U937 cells or human monocytes. This study provides
      evidence for a novel mechanism whereby peroxynitrite may indirectly mediate DNA
      strand scission under inflammatory conditions.

PMID- 20136510
TI  - Oxidative protein folding and the Quiescin-sulfhydryl oxidase family of
      flavoproteins.
AB  - Flavin-linked sulfhydryl oxidases participate in the net generation of disulfide
      bonds during oxidative protein folding in the endoplasmic reticulum. Members of
      the Quiescin-sulfhydryl oxidase (QSOX) family catalyze the facile direct
      introduction of disulfide bonds into unfolded reduced proteins with the reduction
      of molecular oxygen to generate hydrogen peroxide. Current progress in dissecting
      the mechanism of QSOX enzymes is reviewed, with emphasis on the CxxC motifs in
      the thioredoxin and Erv/ALR domains and the involvement of the flavin prosthetic
      group. The tissue distribution and intra- and extracellular location of QSOX
      enzymes are discussed, and suggestions for the physiological role of these
      enzymes are presented. The review compares the substrate specificity and
      catalytic efficiency of the QSOX enzymes with members of the Ero1 family of
      flavin-dependent sulfhydryl oxidases: enzymes believed to play key roles in
      disulfide generation in yeast and higher eukaryotes. Finally, limitations of our
      current understanding of disulfide generation in metazoans are identified and
      questions posed for the future.

PMID- 20136511
TI  - Structural basis for the disulfide relay system in the mitochondrial
      intermembrane space.
AB  - Mitochondria contain two biological membranes. Although reducing agents can
      diffuse from the cytosol into the intermembrane space (IMS) between the outer and
      inner mitochondrial membranes, the IMS has a dedicated disulfide relay system to
      introduce disulfide bonds into mainly small and soluble proteins. This system
      consists of two essential proteins, a disulfide carrier Tim40/Mia40 and a flavin
      dependent sulfhydryl oxidase Erv1, high-resolution structures that have recently
      become available. Tim40/Mia40 transfers disulfide bonds to newly imported IMS
      proteins by dithiol/disulfide exchange reactions involving mixed disulfide
      intermediates. Tight folding by introduction of disulfide bonds prevents egress
      of these small IMS proteins, resulting in their selective retention in the
      compartment. After disulfide transfer from Tim40/Mia40 to substrate proteins,
      Tim40/Mia40 is reoxidized again by Erv1, which is then oxidized by electron
      transfer to either cytochrome c or molecular oxygen. Here we review the recent
      advancement of the knowledge on the mechanism of the disulfide relay system in
      the mitochondrial IMS, especially shedding light on the structural aspects of its
      components.

PMID- 20136512
TI  - Structure, function, and mechanism of thioredoxin proteins.
AB  - Thioredoxins are ubiquitous antioxidant enzymes that play important roles in many
      health-related cellular processes. As such, the fundamental knowledge of how
      these enzymes work is of prime importance for understanding cellular redox
      mechanisms and for laying the ground for the development of future therapeutic
      approaches. Over the past 40 years, a really impressive amount of data has been
      published on thioredoxins. Here, we review the most significant results that have
      contributed to our knowledge regarding the structure, the function, and the
      mechanism of these crucial enzymes.

PMID- 20136513
TI  - The PAPS-independent aryl sulfotransferase and the alternative disulfide bond
      formation system in pathogenic bacteria.
AB  - Sulfurylation of biomolecules (often termed sulfonation or sulfation) has been
      described in many organisms in all kingdoms of life. To date, most studies on
      sulfotransferases, the enzymes catalyzing sulfurylation, have focused on 3'
      phosphate-5'-phosphosulfate (PAPS)-dependent enzymes, which transfer the sulfuryl
      group from this activated anhydride to hydroxyl groups of acceptor molecules. By
      contrast, the PAPS-independent aryl sulfotransferases (ASSTs) from bacteria,
      which catalyze sulfotransfer from phenolic sulfate esters to another phenol in
      the bacterial periplasm, were not well characterized until recently, although
      they were first described in 1986 in a search for nonhepatic sulfurylation
      processes. Recent studies revealed that this unusual class of sulfotransferases
      differs profoundly in both molecular structure and catalytic mechanism from PAPS
      dependent sulfotransferases, and that ASSTs from certain bacterial pathogens are
      upregulated during infection. In this review, we summarize the literature on the
      roles of sulfurylation in prokaryotes and analyze the occurrence of ASSTs and
      their dependence on Dsb proteins catalyzing oxidative folding in the periplasm.
      Furthermore, we discuss structural differences and similarities between aryl
      sulfotransferases and PAPS-dependent sulfotransferases.

PMID- 20136514
TI  - Pomegranate (Punica granatum) seed linolenic acid isomers: concentration
      dependent modulation of estrogen receptor activity.
AB  - Pomegranate (Punica granatum) seed linolenic acid isomers were evaluated as
      selective estrogen receptor modulators (SERMs) in vitro. Punicic acid (PA)
      inhibited (IC(50)) estrogen receptor (ER) alpha at 7.2 microM, ERbeta at 8.8
      microM; alpha-eleostearic acid (AEA) inhibited ERalpha/ERbeta at 6.5/7.8 microM.
      PA (not AEA) agonized ERalpha/ERbeta (EC(50)) at 1.8/2 microM, antagonizing at
      101/80 microM. AEA antagonized ERalpha/ERbeta at 150/140 microM. PA and AEA
      induced ERalpha and ERbeta mRNA expression in MCF-7, but not in MDA-MB-231.
      Overall, the results show PA and AEA are SERMs.

PMID- 20136515
TI  - Effects of melatonin on in vitro development of mouse two-cell embryos cultured
      in HTF medium.
AB  - Melatonin is capable of improving the developmental capacity of ovine, porcine
      and bovine embryos in vitro. However, whether melatonin possesses similar
      benefits to the in vitro mouse embryonic development has yet to be determined. In
      this study, we assessed the effects of various concentrations of melatonin (10-13
      to 10-3 M) on the in-vitro development of mouse embryos cultured in HTF medium
      for 96 hr; embryos cultured without melatonin were used as control. The in vitro
      development of mouse two-cell embryos significantly benefited from treatment with
      melatonin in a concentration-dependent manner. The effects of melatonin on the
      rates of blastocyst formation, hatching/hatched blastocysts and cell number per
      blastocyst were bi-phasic; all significantly increased by melatonin at 10-13 to
      10-5 M and decreased by melatonin at 10-3 M. Maximal benefit of melatonin on in
      vitro mouse 2-cell embryo development was achieved at a concentration of 10-9 M.
      In comparison to control, 10-9 M melatonin increased blastocyst formation rate
      from 48.08 +/- 5.25% to 82.08 +/- 2.34% (p < 0.05), hatched blastocyst rate from
      25.65 +/- 11.79% to 66.47 +/- 4.94% (p < 0.05), and cell number per blastocyst
      62.71 +/- 5.97 to 77.91 +/- 10.63 (p < 0.05). Thus, our datas demonstrated
      firstly that melatonin has beneficial effects on the in vitro development of 2
      cell mouse embryos cultured in HTF medium.

PMID- 20136516
TI  - Selenium and hormone interactions in female patients with Hashimoto disease and
      healthy subjects.
AB  - OBJECTIVE: To examine the correlation structure of parameters expressing selenium
      status, sex hormones secretion and thyroid function in a group of patients with
      Hashimoto disease and healthy female subjects. METHOD: Partial Least Square
      modeling was applied to parameters under study. RESULTS: The correlations between
      relevant parameters were confirmed. Selenoenzyme glutathione peroxidase (GPX3) an
      progesterone played the most significant roles among factors contributing to
      thyroid stimulating hormone and free thyroxine regulation. Additionally, a
      correlation between GPX3 and estradiol was also observed which is in agreement
      with results reported by other authors. Patients with Hashimoto disease had lower
      glutathione peroxidase activities than healthy subjects. CONCLUSION: The
      integrated multivariate approach applied to a new group of patients dissimilar to
      the previous one, was validated by statistical adequacy as well ass meaningful
      interpretation.

PMID- 20136517
TI  - Recombinant decorin ameliorates the pulmonary structure alterations by down
      regulating transforming growth factor-beta1/SMADS signaling in the diabetic rats.
AB  - This study investigated the role of transforming growth factor-beta1 (TGF
      beta1)/Smads signaling in the alterations of lung structure and the effect of the
      exogenous decorin on lung structure modification in streptozotocin (STZ)-induced
      diabetic rats. Seventy-two Sprague-Dawley rats were evenly divided into four
      groups: STZ-induced diabetic rats (diabetic control), decorin adenovirus vector
      (Ad)-treated STZ rats (Ad-DCN), Ad-lacZ-treated STZ rats (Ad-lacZ), and normal
      controls. At 8, 16, and 28 weeks after STZ treatment, haematoxylin-eosin (H&E)
      and Masson's trichrome staining were performed to investigate the histological
      changes of diabetic lungs; Expressions of TGF-beta1 and collagen type IV in the
      diabetic lung were measured by Western blot and immunohistochemistry.
      Phosphorylated Smad2 (P-Smad2), one of the major TGF-beta1 receptor substrates,
      was also detected using Western blot. The histological changes of diabetic lung
      included obvious inflammatory cell infiltration and moderate expanding of
      alveolar septum stained as collagen. Immunolabeled collagen type IV increased in
      the alveolar septa in the diabetic lung. Activities of TGF-beta1/Smads signaling
      increased in the diabetic lung during the 28 weeks of diabetes (p < 0.05 vs.
      control), and positive staining of TGF-beta1 was mainly found in the cytoplasm of
      the infiltrated inflammatory cells. Exogenous decorin effectively suppressed the
      increased activities of TGF-beta1/Smads signaling and partly attenuated collagen
      deposits in the alveolar septum. Increased activity of TGF-beta1/Smads signaling
      might play a critical role in the accumulation of collagen in the diabetic lung.
      The protective effect of decorin in the diabetic lung is at least partly because
      of the down-regulation of the TGF-beta1/Smads signaling.

PMID- 20136518
TI  - The G501C polymorphism of the oxidized low-density lipoprotein-receptor 1 gene is
      associated with acute coronary syndrome in the Han Chinese population.
AB  - Oxidized low-density lipoprotein-receptor 1 (OLR-1) might be involved in the risk
      of atherosclerosis and its complications. Several studies have been carried out
      to explore the role of OLR-1 gene polymorphisms in the risk of coronary artery
      disease. Our study investigated whether the G501C and the 3'UTR C188T
      polymorphisms of the OLR-1 gene were genetic risk factors of acute coronary
      syndrome (ACS) in the Han Chinese population. Significant differences were found
      in genotype frequencies of the OLR-1 G501C polymorphism between 198 ACS patients
      and 204 control individuals. The CC genotype frequency in the ACS group was
      significantly higher than that in the control group (5.6% and 1.5% in ACS
      patients and control subjects, respectively), and the p-value and odds ratio were
      0.028 and 3.911, respectively. Using the CC genotype as a reference, we have
      shown a significant association between carriers of the G allele (GG + GC
      genotypes) and a decreased risk of ACS (p = 0.026, odds ratio = 0.254, 95%
      confidence interval = 0.070-0.924). The OLR-1 G501C polymorphism might be
      associated with ACS in the Han Chinese population.

PMID- 20136519
TI  - The Italian external quality control program for familial adenomatous polyposis
      of the colon: five years of experience.
AB  - Familial adenomatous polyposis is a rare autosomal dominant inherited disease
      (incidence, 1/8000). More than 90% of families affected by familial adenomatous
      polyposis have a mutation in the tumor suppressor gene adenomatous polyposis coli
      (APC). Mutations in this gene are characterized by 100% penetrance, although
      there is a variation in phenotypic expression of the disease. According to a 2004
      survey of the Italian Human Genetic Society, about 264 APC gene molecular genetic
      tests were performed by Italian laboratories per year. The Italian External
      Quality Assessment (IEQA), financially supported by the Ministry of Health and
      coordinated by the Istituto Superiore di Sanita, was started in 2000 to improve
      the quality of molecular genetic tests in Italy. In the frame of the IEQA, about
      50% of public laboratories performing APC gene tests have been monitored. The
      number of responding public laboratories during the 5 years was 6, 7, 7, 7, and 5
      from 2001 to 2006, respectively; on average, 96.3% of samples completely analyzed
      were correctly genotyped. Methods used by laboratories to detect mutation were
      direct sequencing, single-strand conformation polymorphism, protein truncation
      test, and denaturing high-performance liquid chromatography. Written reports were
      not homogeneous among laboratories, although a new form of written report was
      proposed to laboratories in 2004. It will be interesting to monitor the effects
      of the reporting model and the output of this educational action in the future.

PMID- 20136520
TI  - Dynamics of hearing status in closed head injury.
AB  - Hearing impairment can be one of the more subtle deficits seen after closed head
      injury (CHI), and it may not be diagnosed until late in the recovery phase if at
      all. Most studies have assessed patients immediately after CHI. Repeated
      assessments at regular intervals were not performed in the majority of studies
      done to assess whether any initial hearing loss regressed or progressed. Follow
      up at later stages will shed more light on the audiological consequences of CHI.
      The aim of this study was to analyze the long-term audiological consequences of
      CHI. A total of 290 subjects with CHI were chosen and followed-up at 3, 6, and 12
      months. The audiological test battery comprised pure tone audiometry (PTA),
      speech audiometry, tympanometry, auditory brainstem response (ABR), and middle
      latency response (MLR), and was administered to all subjects. The data from 96
      subjects who completed all three follow-ups were analyzed for tympanometry, ABR,
      and MLR. However, for PTA and speech audiometry, data from only 76 subjects were
      analyzed, as unconscious and disoriented subjects could not undergo these tests
      at initial testing. The results revealed that hearing status after CHI varies,
      and that at follow-up significant changes in hearing were seen. Hearing of low
      frequencies improved, due primarily to improvements in middle ear function.
      Significant changes in ABR latencies and MLR amplitudes were also observed. This
      reflects the unequal rates of recovery observed in the different parts of the
      central auditory nervous system.

PMID- 20136521
TI  - Home-based palliative care services for underserved populations.
AB  - BACKGROUND: Kokua Kalihi Valley is one of the first federally qualified community
      health centers offering home-based palliative care (HBPC). Kokua Kalihi Valley
      serves low-income, immigrant populations from Asia and the Pacific Islands, whose
      end-of-life needs are rarely addressed. Our team includes a palliative medicine
      physician, nurse, case manager, psychologist, interpreter, and volunteers.
      OBJECTIVES: The purpose of this Institutional Review Board-approved study was to
      measure symptom relief and quality of life, resource utilization, and
      satisfaction with HBPC. METHODS: Over 12 months, 91 people including 46 patients
      with chronic advanced illnesses and 45 corresponding primary caregivers were
      enrolled. Data were collected prospectively, upon admission, and repeatedly
      thereafter, using the Missoula-Vitas Quality of Life Index, the Edmonton Symptom
      Assessment Scale, and the Palliative Performance Scale. Utilization of resources
      was tracked, including case management, hospice, emergency department, and
      hospital visits. RESULTS: The median age was 71 years, and more than half had
      chronic neurodegenerative conditions. Most patients (98%) were minority,
      including Samoans, Filipinos, Japanese, Micronesians, and Hawaiians. Median stay
      in HBPC was 7 months, with a median of 3.5 visits. Approximately 25% of patients
      enrolled in hospice (median stay 67.5 days). There was a decrease in
      hospitalizations (p = 0.002) after HBPC admission. Discussions and documentation
      of end-of-life wishes increased from 50% to 90% (p < 0.01). Caregiver
      satisfaction with HBPC was high. CONCLUSION: Data on outcomes and quality
      indicators of HBPC programs are scant, especially among immigrant Asian and
      Pacific Islanders patients. Our experience demonstrates the effectiveness of
      palliative care approaches in this population.

PMID- 20136522
TI  - Gender-based differences in long-term outcome after ST-elevation myocardial
      infarction in patients treated with percutaneous coronary intervention.
AB  - BACKGROUND: In the era of fibrinolysis, women suffered from higher early and late
      mortality rates than men after acute ST-elevation myocardial infarction (STEMI).
      Primary percutaneous coronary intervention (PCI) has been determined to be the
      most effective therapy strategy in STEMI. It is not clear if female gender is an
      independent predictor of a worse long-term prognosis among patients who were
      systematically treated with PCI. We, therefore, examined the effect of PCI on
      long-term outcome between women and men. METHODS: Between 1999 and 2001, 500
      consecutive patients at the Wuppertal Heart Centre were treated with PCI after
      acute STEMI. A long-term follow-up (up to 7 years) was achieved in 97% of the
      patients. RESULTS: In comparison to men, women were 7 years older (65 +/- 12 vs.
      58 +/- 11) and had significantly more diabetes mellitus. The time between onset
      of symptoms and intervention tended to be longer in women than men. There was no
      difference in 30-day mortality (8.9% vs. 6.6%), cardiac late mortality (3.6% vs.
      3.2%), and long-term cardiac overall mortality up to 7 years (12.1% vs. 9.6%).
      Stepwise regression analysis did not identify female gender as an independent
      predictor of late mortality. The quality of life was comparable. CONCLUSIONS:
      There was no gender-related difference in the long-term outcome if patients were
      sytematically treated with PCI in STEMI. PCI in STEMI has a long-lasting positive
      effect in women and should, therefore, be considered the treatment of choice for
      women with acute myocardial infarction.

PMID- 20136523
TI  - Interdisciplinary staffing patterns: do for-profit and nonprofit hospices differ?
AB  - BACKGROUND: Interdisciplinary care is fundamental to the hospice philosophy and
      is a key component of high-quality hospice care. However, little is known about
      how hospices differ in their interdisciplinary staffing patterns, particularly
      across nonprofit and for-profit hospices. The purpose of this study was to
      examine potential differences in the staffing patterns of for-profit and
      nonprofit hospices. SUBJECTS AND DESIGN: Using the 2006 Medicare Provider of
      Services (POS) survey, we conducted a cross-sectional analysis of staffing
      patterns within Medicare-certified hospices operating in the United States in
      2006. In bivariate and multivariable analyses, we examined differences in
      staffing patterns measured by the existence of a full range of interdisciplinary
      staff (defined as having at least 1 full-time equivalent (FTE) staff in each of 4
      disciplines ascertained by the survey: physician, nursing, psychosocial, and home
      health aide) and by the professional mix of staff within each discipline.
      RESULTS: For-profit hospices had a winder range of paid staff but there were no
      differences by ownerships when volunteer staff were included. For-profit hospices
      had significantly fewer registered nurse FTEs as a proportion of nursing staff,
      fewer medical social worker FTEs as a proportion of psychosocial staff, and fewer
      clinician FTEs as a proportion of total staff (p values <0.05). Compared to
      nonprofit hospices, for-profit and government-owned hospices also used
      proportionally fewer volunteer FTEs. CONCLUSIONS: Hospice staffing patterns
      differed significantly by ownership type. Future research should evaluate the
      impact of these differences on quality of care and satisfaction among patients
      and families using hospice.

PMID- 20136524
TI  - Cell-laden hydrogel constructs of hyaluronic acid, collagen, and laminin for
      neural tissue engineering.
AB  - Various neural tissue engineering approaches that are under development for
      applications ranging from guidance conduits to cell-based therapies rely on the
      ability to encapsulate cells in three-dimensional (3D) scaffolds. Schwann cells
      play a key role in peripheral nerve regeneration by forming oriented paths for
      regrowing axons. We have engineered collagen and hyaluronic acid interpenetrating
      polymer network (IPN) hydrogels with and without laminin as a 3D culture system
      for Schwann cells in an attempt to devise novel neural regeneration therapies.
      Encapsulation of Schwann cells in 3D hydrogel constructs did not affect cell
      viability and cells were viable for 2 weeks in all hydrogel samples. Moreover, in
      hydrogels with high cell density, cells underwent spreading and proliferation,
      and the cell numbers increased by day 14 as assessed qualitatively using a
      Live/dead assay and scanning electron microscopy (SEM), and quantitatively using
      a CellTiter 96 AQueous non-radioactive cell proliferation assay. In some cases,
      the cells aligned parallel to each other and formed structures reminiscent of
      Bands of Bungner. Schwann cells in cell-hydrogel constructs with high cell
      density were not only viable but also actively secreting nerve growth factor and
      brain-derived neurotrophic factor. Of particular importance was the observation
      that addition of laminin in these hydrogels increased the overall production of
      nerve growth factor and brain-derived neurotrophic factor from the cells.
      Immunostaining revealed that S100 expression and cell spreading were
      differentially affected by cell density. Interestingly, in the co-culture of
      dissociated neurons with Schwann cells, neurons were able to extend neurites and
      some neurites were observed to follow Schwann cells. Therefore, we conclude that
      Schwann cells encapsulated in the 3D extracellular matrix-mimicking hydrogel may
      hold promise in nerve regeneration therapies and may form the basis for
      understanding the underlying mechanisms of Schwann cell interactions with neurons
      and various extracellular matrix components.

PMID- 20136525
TI  - DNA carrier testing and newborn screening for maple syrup urine disease in Old
      Order Mennonite communities.
AB  - Maple syrup urine disease (MSUD) is an inherited metabolic disorder caused by
      mutations in the branched chain alpha-keto acid dehydrogenase complex. Worldwide
      incidence of MSUD is 1:225,000 live births. However, within Old Order Mennonite
      communities, the incidence is 1:150 live births and results from a common
      tyrosine to asparagine substitution (Y438N) in the E1alpha subunit of branched
      chain alpha-keto acid dehydrogenase. We developed a new DNA diagnostic assay
      utilizing TaqMan technology and compared its efficacy, sensitivity, and duration
      with an existing polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) assay. Carrier testing was performed by both TaqMan
      technology and PCR-RFLP on DNA isolated from buccal swabs of 160 individuals as
      well as from buccal swabs and blood spots of nine at-risk newborns; assay time,
      sensitivity, and reliability were also evaluated. The TaqMan assay, like the PCR
      RFLP assay, accurately determined Y438N E1alpha allele status. However, the
      TaqMan assay appeared (1) more sensitive than the PCR-RFLP assay, requiring 10
      fold less DNA (10 ng) to reliably determine genotype status and (2) faster,
      reducing the assay time required for diagnosis from approximately 12 to 5 h.
      TaqMan technology allowed more rapid DNA diagnoses of MSUD in the neonate,
      thereby reducing the likelihood of neurological impairment while enhancing health
      and prognosis for affected infants.

PMID- 20136526
TI  - Williams-Beuren syndrome: diagnosis by polymorphic markers.
AB  - Williams-Beuren syndrome (WBS) is caused by a 1-2 Mb microdeletion in the region
      7q11.23. The clinical presentation may vary and most of the connective tissue
      abnormalities can be explained by the haploinsufficiency of the ELN gene in this
      region. The purpose of this study was to determine the value of a polymerase
      chain reaction assay that uses three polymorphic markers to detect the
      microdeletion and compare the clinical features. Thirty-two patients with WBS
      were ascertained accordingly to clinical diagnostic criteria. The markers
      D7S1870, ELN 17/exon 18, and Hei 1.3/1.4 were designed to detect the
      heterozygosity in the region 7q11.23. The three markers were informative in 78%
      and uninformative in 22% of the cases. The most informative marker (69%) was
      D7S1870, followed by Hei (55%) and ELN 17/exon 18 (44%). The microdeletion was
      present in 56% and absent in 22% of patients. The craniofacial and cardiovascular
      abnormalities did not have significant statistical differences in the cases with
      and without microdeletion. Two of the syndrome characteristics (an overfriendly
      personality and hyperacusis) were more frequent in the microdeletion group and
      these differences were statistically significant (p = 0.006 and p = 0.02,
      respectively). Polymorphic markers might be a good alternative for the molecular
      diagnosis of WBS in centers where fluorescence in situ hybridization analysis is
      not available.

PMID- 20136527
TI  - Genomic and linguistic affinities: a study of allelic and haplotype diversity at
      DRD2 locus among the tribes of Gujarat, western India.
AB  - Do genetic and linguistic affinities necessarily go hand in hand? An attempt has
      been made in the present work to explore this dimension of population structure
      using three evolutionarily important TaqI sites (TaqI A, TaqI B, and TaqI D) on
      the dopamine receptor D2 (DRD2) locus. For the first time, DNA samples from 612
      unrelated individuals belonging to 11 Indo-European-speaking tribal population
      groups of Gujarat, western India, have been analyzed for these three sites. All
      the three sites are found to be polymorphic with greater interpopulation
      variation seen at the TaqI B site. The average heterozygosity for the haplotype
      system has been found to be high in the populations under study. Most of the
      populations share six of the eight haplotypes pointing toward underlying genetic
      uniformity, which is further reaffirmed by regression analysis of heterozygosity
      on genetic distance. The frequency of ancestral haplotype B2D2A1 is found to
      range between 1.9% and 15.9%. Linkage disequilibrium between TaqI B and TaqI D
      sites and between TaqI B and TaqI A sites is statistically significant in all but
      one population. Our findings reveal strong affinities between Indo-European
      speaking tribal groups of Gujarat and Dravidian-speaking tribal groups of South
      India, suggesting that genetic affinities may not necessarily be dependent on
      linguistic similarities.

PMID- 20136528
TI  - Risk management in mental health: applying lessons from commercial aviation.
AB  - OBJECTIVE: Risk management in mental health focuses on risks in patients and
      fails to predict rare but catastrophic events such as suicide. Commercial
      aviation has a similar task in preventing rare but catastrophic accidents. This
      article describes the systems in place in commercial aviation that allows that
      industry to prevent disasters and contrasts this with the situation in mental
      health. CONCLUSIONS: In mental health we should learn from commercial aviation by
      having: national policies to promote patient safety; a national body responsible
      for implementing this policy which maintains a database of safety occurrences,
      sets targets and investigates adverse outcomes; legislation in place which
      encourages clinicians to report safety occurrences; and a common method and
      language for investigating safety occurrences.

PMID- 20136529
TI  - Evaluation of the Claassen Institute of Psychiatry for Medical Students.
AB  - OBJECTIVE: Psychiatric educators need to develop innovative strategies to attract
      more medical students to psychiatry. In 2008, the University of Western Australia
      held the inaugural Claassen Institute of Psychiatry for Medical Students. This
      novel program aimed to increase students' level of interest in psychiatry as a
      career opportunity. METHOD: Students completed baseline and follow-up
      questionnaires. Questions were rated on a scale of 1 to 10. RESULTS: Thirty
      students participated. The average age was 25.5 years and 11 were male. The mean
      interest and knowledge in psychiatry from baseline to follow-up increased from
      7.8 to 8.9 and 5.8 to 7.3, respectively. Mean interest and knowledge in
      neurosciences increased from 6.9 to 7.7 and 4.3 to 6.2, respectively. Paired t
      sample tests were significant (p<0.001). Students 'definitely considering' a
      career in psychiatry increased by 20% overall from baseline to follow-up.
      Enjoyment and organization of the week were rated highly. CONCLUSIONS: The
      Institute is an innovative teaching strategy targeted towards medical students.
      The program increased the level of interest shown by students in psychiatry as a
      career. The Institute may positively contribute to recruitment of students to
      psychiatry training programs and it is planned to run it annually.

PMID- 20136530
TI  - Syphilis, sex and psychiatry, 1789-1925: Part 1.
AB  - OBJECTIVES: Syphilis has changed the course of history, shaped the path of
      medicine and had more influence on psychiatry than any other illness. This paper,
      part one of a two-part series, investigates the historical, social and cultural
      aspects of the interaction of syphilis and psychiatry. CONCLUSION: Syphilis did
      not manifest as a psychiatric illness until the French Revolution. At the time,
      the Pinel School was focussing on the environment and moral therapy. Bayle, who
      made the first discovery of the cause of a psychiatric disease - chronic
      arachnoiditis - paid the price for his discovery by being driven from psychiatry.
      The 19th century led to the rise of a new medical polymath: the syphilologist - a
      specialist in every aspect of a disease that showed a remarkable capacity to
      affect every organ and tissue in the body and produce symptoms resembling other
      illnesses. The field was dominated by Frenchmen, Philippe Ricord and Alfred
      Fournier, and Englishman Jonathan Hutchinson. A middle-class illness,
      neurosyphilis struck at the heart of the class interests - property. This reeked
      havoc with the family business or finances, causing considerable distress to
      their relatives. General paresis of the insane became associated in the public
      eye with creative, intellectual or philosophical activity. It affected a long
      list of artists, writers and musicians, including Oscar Wilde, Robert Schumann,
      Baudelaire, Schubert and Ivan the Terrible. While the features of syphilis were
      delineated, confirmation remained elusive and neurosyphilis continued to hide its
      secrets. It remained the grand cause that defined psychiatry and it was not until
      the middle of the 20th century that it ceased to play a part in the daily life of
      doctors in psychiatric wards.

PMID- 20136531
TI  - Syphilis, sex and psychiatry, 1789-1925: Part 2.
AB  - OBJECTIVES: Syphilis has changed the course of history, shaped the path of
      medicine and had more influence on psychiatry than any other illness. This paper,
      part two of a two-part series, investigates the historical, social and cultural
      aspects of the interaction of syphilis and psychiatry. CONCLUSION: By the end of
      the 19th century, social changes such as population growth, mass migration from
      Eastern Europe and technological developments led to a great rise in syphilis. By
      1900, it was estimated that 5-20% of the population of Europe and the USA had, or
      would have, syphilis. By 1914, there were over 100,00 new cases and 3 million
      cases of syphilis in Great Britain. There was a constant interaction between
      syphilis, prostitution and sexual crime; it was the likely motivation for the
      Jack the Ripper murders, if not many in the next century. The idea of hereditary
      syphilis fitted perfectly into the theory of degeneration and coursed through
      psychiatry and caught the attention of Adolf Hitler, facilitating his antisemitic
      paranoia. Psychiatric progress passed to the German school, led by Kraepelin who
      did his first research into the symptoms and course of neurosyphilis. In 1906,
      Wasserman's serological test for syphilis showed that latent lesions could be
      present. Any doubt about the cause of syphilis was finally eliminated when
      Noguchi and Moore demonstrated the presence of treponema pallidum in paretic
      brains in 1913. German academic psychiatry defined psychiatric practice for the
      next century but malariotherapy, the first physical treatment in psychiatry, was
      announced by Julius Wagner-Juarreg in Vienna in 1917, bringing hope to the
      incurable and destroying the climate of therapeutic nihilism that haunted
      psychiatry. The first trial of malariotherapy in Australia was done by Reginald
      Ellery at Mont Park Hospital In 1927 in Melbourne. The discovery of penicillin
      was a caesura, ending malariotherapy and leading many to regard syphilis as a
      night-extinct illness, but this turned out to be an illusion. Syphilis is
      returning in new forms in tandem with the AIDS epidemic. Written-off endlessly by
      its obituarists, syphilis abides.

PMID- 20136532
TI  - Lord Clive did not suffer a mood disorder.
AB  - OBJECTIVE: We aimed to clarify questions regarding Lord Clive's early suicidal
      behavior and mental health. METHOD: We examined various historical texts.
      RESULTS: Clive suffered gallstones with episodes of cholecystitis. We could find
      no evidence that Clive engaged in suicidal behavior in his early life, nor
      evidence of a mood disorder (depression or bipolar disorder) throughout his life
      or at the time of his death. CONCLUSIONS: Although reports of famous people who
      have suffered mental disorders may help to decrease the stigma associated with
      these conditions, there is a need for caution before make such a diagnosis. In
      the case of Lord Clive, we could find no evidence of a major mood disorder.

PMID- 20136533
TI  - Self-reported side effects in children and adolescents taking risperidone.
AB  - OBJECTIVE: We aimed to describe medication side effects in a cross-section of
      young people taking low-dose risperidone, using a self-report measure. METHODS:
      The Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) was
      completed by 66 patients aged between 6 and 18 years who had been taking low-dose
      risperidone (alone or in conjunction with other medications) for up to 13 years.
      RESULTS: Young persons, overall, seemed to tolerate risperidone well, but longer
      exposure to the medication was associated with higher side effect levels,
      particularly for the psychic (pertaining to mind and emotion) and extrapyramidal
      subscales. The most common complaints related to psychic side effects, such as
      tiredness, difficulty concentrating, difficulty remembering things and increased
      dreaming. CONCLUSIONS: Clinicians need to monitor the side effects of young
      patients taking low doses of risperidone, and other psychotropics, and maintain
      vigilance in those who have been taking medication for extended periods.

PMID- 20136534
TI  - An observer's typology of suicide.
AB  - OBJECTIVE: The aim of this study was to present a typology of suicide which may
      assist in future thinking about suicide. CONCLUSION: A typology is described in
      which suicide is conceptualized as the result of a predicament (an uncomfortable
      set of circumstances from which there are limited escape options). Two
      predicaments are proposed, one when mental disorder is present and is the driver
      of completed suicide, and the other when mental disorder is absent, and
      environmental factors are the drivers of completed suicide. Each predicament is
      divided into two boxes according to the view of the observer, one in which the
      predicament is very clearly, and the other in which the predicament is less
      clearly the driver of the suicide. Examples are provided.

PMID- 20136535
TI  - Vanuatu: happiest nation on earth, mental health and the Church.
AB  - OBJECTIVE: The aim of this paper was to gain an understanding of the mental
      health needs and services in Vanuatu, and examine the importance of the Church in
      the lives of the local people and the part that the Church can play in mental
      health service delivery. METHOD: The author visited Vanuatu to gain an
      understanding of the mental health needs and services in Vanuatu. This was
      followed by interaction with a number of churches to find out the views of church
      leaders about mental illness and their interest to learn about mental illness. A
      questionnaire was completed by 80 individuals who were also involved in some
      training. RESULTS: There was a widely held view that mental illness was due to a
      weak faith, sin or demon possession. However, there is a desire and an interest
      among churches to have a better understanding about mental illness. CONCLUSION:
      Churches in Vanuatu can and need to be mobilized to make mental health service
      delivery successful in the country.

PMID- 20136539
TI  - National registration of medical practitioners.

PMID- 20136541
TI  - Disturbance of confidence as the mechanism underpinning depressive illness.

PMID- 20136542
TI  - The short stay unit: a potential solution in crisis intervention.

PMID- 20136543
TI  - Fear of the yawning mother: a case of misophonia.

PMID- 20136544
TI  - Travel to a hot climate as a trigger for NMS.

PMID- 20136549
TI  - First report on HLA-DPB1 gene allelic distribution in the general Lebanese
      population.
AB  - AIMS: Interest in the importance of the HLA-DPB1 gene has increased lately,
      especially in transplantation outcomes in addition to other HLA CII molecules.
      This is the first study that assesses HLA-DPB1 typing among healthy Lebanese
      individuals. METHODS: The HLA-DPB1 alleles were detected using the polymerase
      chain reaction/sequence-specific priming method and our study included 130
      individuals. HLA-DPB1 was determined in different ethnic groups and in relation
      to various clinical entities. RESULTS: We compared our data with the existing
      literature and found an interesting similarity between the Lebanese and Greek
      populations with highly specific alleles not reported in other communities.
      CONCLUSION: Our study will form the basis for further research to study the
      correlation between HLA-DPB1 and various clinical entities as well as a primer
      study for other transplantation centers.

PMID- 20136550
TI  - Scientific excellence in applying sex- and gender-sensitive methods in biomedical
      and health research.
AB  - Despite regulations, the attention paid to sex and gender in biomedical and
      health research is far from optimal. Researchers often recognize the importance
      of incorporating sex and gender issues in general but fail to see the
      applicability to their own research. This can have severe consequences and
      impedes gender equity in healthcare. More hands-on approaches are needed that
      stimulate scientists to integrate sex and gender aspects into their research. The
      present work is based on the contents of a workshop developed by the authors that
      serves as such a hands-on method. It aims at familiarizing a broad range of
      scientists in the field of biomedical and health research with the basics of
      conducting sex- and gender-sensitive research. In addition to clarifying
      concepts, it serves to provide a general introduction to sex- and gender
      sensitive methods. To this end, challenges in pitfalls conducting sex- and gender
      sensitive research, originally identified in the social sciences, are translated
      to the practice of biomedical and health research. Implications and applicability
      to all areas of biomedical and health research are shown by providing
      illustrative examples. Finally, a tool is presented that allows for the detection
      of sex and gender bias throughout all phases of the research process and shows
      how this bias can be overcome through sex- and gender-sensitive (1) relevance
      checking, (2) literature search, (3) formulation of research questions and
      hypotheses, (4) research methods and sample, (5) data analysis and
      interpretation, (6) reporting, and (7) conclusions and recommendations.

PMID- 20136551
TI  - Epigenetic basis for fetal origins of age-related disease.
AB  - The current concept of fetal origins of adult diseases describes in utero
      programming, or adaptation to a spectrum of adverse environmental conditions that
      ultimately leads to increased susceptibility to age-related diseases (e.g., type
      2 diabetes and cardiovascular disease) later in life. Although the precise
      mechanism of this biological memory remains unclear, mounting evidence suggests
      an epigenetic basis. The increased susceptibility to chronic disease and
      involvement of multiple organ systems that is observed is analogous to the
      decline in resistance to disease that is typical of normal aging. Although the
      cumulative environment over the course of a lifetime can induce increasing
      epigenetic dysregulation, we propose that adverse events that occur during early
      development can induce significant additional dysregulation of the epigenome.
      Here, we describe the current evidence for fetal origins of adult disease and the
      associated role of epigenetic dysregulation. In addition, we present a new
      perspective on the induction of epigenetic alterations in utero, which
      subsequently lead to an aging phenotype marked by increased susceptibility to age
      related diseases.

PMID- 20136552
TI  - Racial disparities in contraceptive use between student and nonstudent
      populations.
AB  - BACKGROUND: In order to explore opportunities for eliminating the persistent
      racial disparities in contraceptive use between Caucasian and African American
      young adults, we examined whether student populations display a reduced racial
      disparity in overall contraceptive use and use of highly effective
      contraceptives. METHODS: Using data collected from the Behavioral Risk Factor
      Surveillance System (BRFSS) over 3 years, we conducted multivariate analysis to
      compare racial disparities in contraceptive use in the nonstudent, young adult
      (18-24 years) population with those in the student population. Analyses are
      controlled for age, income, education, and insurance status. RESULTS: Both
      African American students and nonstudents demonstrate a trend of being more
      likely than their Caucasian counterparts to forego use of contraception, but the
      findings are statistically significant only for the impact of race on nonstudents
      (OR = 1.45, 95% CI 1.15-1.84). However, African American students show a greater
      disparity in using effective contraceptive methods compared with Caucasian peers
      (OR = 0.459, 95% CI 0.316-0.668) than in the nonstudent population (OR = 0.591,
      95% CI 0.488-0.715). CONCLUSIONS: Although race is not significant for predicting
      overall use of contraceptives among students, racial disparities are magnified
      among student populations with regard to use of highly effective contraceptives.
      Contraceptive counseling for African American young adults should focus on method
      effectiveness and consider additional issues, such as insurance coverage for
      contraceptives. For students, targeted counseling or interventions may be
      required.

PMID- 20136553
TI  - Relative effects of tamoxifen, raloxifene, and conjugated equine estrogens on
      cognition.
AB  - OBJECTIVE: To compare the relative effects of conjugated equine estrogens (CEE),
      raloxifene, and tamoxifen therapies on cognition among women aged > or =65 years.
      METHODS: Annual Modified Mini-Mental State (3MS) examinations were used to assess
      global cognitive function in the two randomized placebo-controlled clinical
      trials of CEE therapies of the Women's Health Initiative Memory Study (WHIMS) and
      the Cognition in the Study of Tamoxifen and Raloxifene (CoSTAR). Analyses were
      limited to women who had 3MS testing at baseline and the first 3 years of follow
      up and, because of potential ethnic-related differences between studies, to
      Caucasian women (WHIMS n = 6211, CoSTAR n = 250). Covariate adjustment was used
      to compare the postrandomization mean 3MS scores among the three active therapies
      with placebo therapy while controlling for differences between groups with
      respect to dementia risk factors. RESULTS: At baseline, the average (SD) 3MS
      scores by group were 95.24 (4.28) for placebo, 95.19 (4.33) for CEE, 94.60 (4.76)
      for raloxifene, and 95.02 (4.03) for tamoxifen. Compared with placebo, each
      active therapy was associated with a small mean relative deficit in 3MS scores of
      < or =0.5 units, which was fairly consistent between women with and without prior
      hysterectomy. Relative deficits were slightly greater for tamoxifen (p = 0.001)
      and less marked for raloxifene (p = 0.06) and CEE (p = 0.02) therapies. Relative
      deficits appeared to be greater among women with lower baseline 3MS scores: p =
      0.009 (tamoxifen), p = 0.08 (raloxifene), and p = 0.03 (CEE). CONCLUSIONS:
      Although unmeasured differences between trials may have confounded analyses,
      these findings raise the possibility that both tamoxifen and raloxifene adversely
      affect cognitive function in older women; however, the magnitude of the effect is
      small, and the long-term consequences are unknown.

PMID- 20136554
TI  - Identification of a novel candidate locus for juvenile idiopathic arthritis at
      14q13.2 in the Latvian population by association analysis with microsatellite
      markers.
AB  - To identify novel juvenile idiopathic arthritis (JIA) susceptibility loci, a 270
      kb genomic region encompassing FAM177A1, KIAA0391, and PSMA6 genes was genotyped
      in 97 oligoarthritis (JIoA) and 50 polyarthritis (JIpA) patients and 230
      individuals without autoimmune disorders by five microsatellites (MS) previously
      described as HSMS markers of the 14q13.2 region. Direct sequencing revealed two
      variable components of the (CAA)(n)(A)(m) motif in HSMS602 marker (FAM177A1
      gene). Repeat (AC)(5)AT(AC)(n) of the HSMS701 (KIAA0391 gene) was variable in the
      Latvian population only in its downstream part. Allele (AC)(5)AT(AC)(15) of
      HSMS701 was found to be strongly associated with JIA (p = 4.91 x 10(-5), odds
      ratio [OR] = 18.87) and modestly associated with JIpA (p = 1.64 x 10(-3), OR =
      15.69). Alleles (AC)(5)AT(AC)(18) of HSMS701 and (TG)(10) of HSMS702 appear to be
      JIA and JIoA risk factors (p = 1.09 x 10(-3), OR = 2.64 and p = 2.00 x 10(-3), OR
      = 7.67, respectively), but allele 168 bp of HSMS602 (p = 9.02 x 10(-4), OR =
      0.35) appears to be protective. Two heterozygote genotypes (TG)(20/23) of the
      HSMS006 and (AC)(22/23) of the HSMS801 showed association with JIA (p < 2 x 10(
      3)), but homozygote (TG)(19/19) was found to be protective (p = 5.41 x 10(-4), OR
      = 0.12). Our results define an additional susceptibility locus for JIA at the
      14q13.2 genomic region encompassing KIAA0391 and PSMA6 genes.

PMID- 20136555
TI  - Splenic injury during percutaneous nephrolithotomy: a case report with novel
      management technique.
AB  - We describe a case of a splenic injury caused by a transsplenic percutaneous
      nephrostomy tract. The case was completed without incident and the nephrostomy
      tube was noted to traverse the spleen on routine postoperative imaging. This rare
      complication was managed by deposition of Gelfoam((R)) pledgets along the
      transsplenic nephrostomy tract and placement of a ureteral stent. This novel
      management technique has not been previously described in the literature and was
      successful in the conservative treatment of the uncommon complication of splenic
      injury during percutaneous nephrolithotomy.

PMID- 20136556
TI  - Trends in injection drug use among pregnant women admitted into drug treatment:
      1994-2006.
AB  - OBJECTIVE: To describe trends in the regional and demographic characteristics of
      injection drug use (IDU) during pregnancy. METHODS: Data were obtained from the
      Treatment Episode Data Set (TEDS), an administrative data set that captures
      admissions to federally funded treatment centers in the United States.
      Demographic and treatment-related measures were examined and compared between
      injection drug and noninjection drug admissions. The results were stratified by
      year of admission to assess trends over time. RESULTS: From 1994 to 2006, there
      were 239,511 admissions of pregnant women, of whom 34,717 (14.4%) reported IDU.
      There was little change in the proportion of injecting from year to year.
      Compared with admissions of noninjecting pregnant women, a greater proportion of
      injection drug users were white (68.5 vs. 48.6%), reported heroin use (70.0% vs.
      13.2%), and had no health insurance (48.2% vs. 40.2%). Over the time period, the
      proportion of injection drug users was seen to spread from the West to the South
      and Northeast for heroin and to the Midwest for amphetamines. CONCLUSIONS: IDU
      among pregnant women in drug treatment remains a significant public health issue,
      especially among white women.

PMID- 20136557
TI  - Wireless image streaming in mobile ultrasound.
AB  - This work evaluates the feasibility of using 802.11 g ad hoc and 3G cellular
      broadband networks to wirelessly stream ultrasound video in real-time.
      Telemedicine ultrasound applications in events such as disaster relief and first
      response triage can incorporate these technologies, enabling onsite medical
      personnel to receive assistance with diagnostic decisions by remote medical
      experts. The H.264 scalable video codec was used to encode echocardiographic
      video streams at various image resolutions (video graphics array [VGA] and
      quarter video graphics array [QVGA]) and frame rates (10, 15, 20, and 30
      frames/s). The video stream was transmitted using 802.11 g and 3G cellular
      technologies, and pertinent transmission parameters such as data rate, packet
      loss, delay jitter, and latency were measured. 802.11 g permits high frame rate
      and VGA resolution and has low latency and jitter, but it is suitable only for
      short communication ranges, whereas the 3G cellular network allows medium to low
      frame rate streaming at QVGA image resolution with medium latency. However, video
      streaming can take place from any location with 3G service to any other site with
      Internet connectivity. The transmitted ultrasound video streams were subsequently
      recorded and evaluated by physicians with expertise in medical ultrasonography
      who evaluated the diagnostic value of the received video streams relative to the
      original videos. They expressed the opinion that image quality in the case of
      both 802.11 g and 3G was fully to adequately preserved, but missed frames could
      momentarily decrease the diagnostic value. This research demonstrates that 3G and
      802.11 g wireless networks combined with efficient video compression make
      diagnostically valuable wireless streaming of ultrasound video feasible.

PMID- 20136558
TI  - Economic analysis of telemedicine and the teledermatology paradigm.
AB  - Abstract Economic considerations are an important component in the planning and
      execution of a telemedicine program. The goal of this review is to familiarize
      readers with economic concepts relevant to the analysis of telemedicine programs.
      Economic perspectives, cost attribution, types of economic analysis, and commonly
      encountered problems will be discussed as they pertain to telemedicine. Societal
      perspectives, healthcare system perspectives, patient perspectives, fixed versus
      variable costs, labor costs, and distinctions between cost-effectiveness analyses
      and other types of economic analysis also will be examined. Examples from the
      teledermatology literature will be used as a paradigm to illustrate how these
      concepts are integrated into existing analyses of teledermatology systems.
      Teledermatology shows promise as a cost-saving healthcare delivery system with
      outcomes comparable to or better than those of conventional care processes. The
      literature also points out the importance of economic perspectives in the
      findings and interpretation of an analysis.

PMID- 20136559
TI  - Anti-inflammatory and antioxidant effects of Jeevaneeya Rasayana: an ayurvedic
      polyherbal formulation on acute and chronic models of inflammation.
AB  - The present study was aimed to establish the efficacy of Jeevaneeya Rasayana
      (JR), an ayurvedic polyherbal formulation, in adjuvant-induced arthritic (AIA)
      rat model with reference to mediators of inflammation. The methanolic (MJR),
      ethanolic (EJR), and water extracts (WJR) of JR were prepared and their anti
      inflammatory activity in carrageenan-induced acute model was evaluated. MJR at a
      dose of 25 mg/kg showed significantly higher anti-inflammatory effect than EJR,
      WJR, and standard drug diclofenac. MJR also significantly decreased the paw edema
      in AIA rats. Activities of cyclooxygenase, 5-lipoxygenase, and myeloperoxidase
      were decreased significantly on treatment with MJR. Supplementation with MJR
      increases the activities of antioxidant enzymes and the level of glutathione
      content. The increment in the concentration of C-reactive protein, thiobarbituric
      acid reactive substance, and ceruloplasmin observed in arthritic rats were found
      to be significantly restored in MJR treated rats. Thus, the results demonstrated
      the potential beneficiary effect of methanolic extract of Jeevaneeya Rasayana on
      acute and chronic models of inflammation.

PMID- 20136560
TI  - Sex differences in the use of the Internet as a source of health information
      among adolescents.
AB  - BACKGROUND: The Internet is a fundamental part of the day-to-day lives of
      adolescents. Faced with the difficulties of accessing conventional health
      services, adolescents use the Internet as a confidential and safe means of
      accessing information about health issues. OBJECTIVES: To describe sex
      differences in the way in which adolescents search for health information on the
      Internet. METHODS: Cross-sectional survey with a questionnaire administered by an
      interviewer. Sociodemographic and health variables and those related to the
      conditions of access and use of information and communication technologies were
      gathered (multivariate analysis). RESULTS: About 823 school-age youths were
      interviewed (21 questionnaires were discarded due to low quality), among whom
      54.1% were girls and 46% were boys. The girls had a lower self-assessed level of
      health than the boys. About 86.5% of the girls used the Internet, compared with
      89.9% of the boys (p = 0.155). About 21.7% and 48.3% of the boys used it
      daily/weekly and occasionally, respectively, compared with 17.9% and 59.1% of the
      girls who used it daily/weekly and occasionally, respectively. The multivariate
      analysis shows that girls (odds ratio [OR], 1.709; 95% confidence interval [CI],
      1.277-2.287), those in their last year of secondary school (OR, 1.369; 95% CI,
      1.025-1.830) and those who had visited the doctor most often the previous year
      (OR, 1.061; 95% CI, 1.017-1.107), were statistically significantly more likely to
      search for health information on the Internet. CONCLUSION: Adolescent girls tend
      to seek more information about health than boys and there are differences in the
      way in which these girls search for health information on the Internet. The
      Internet provides adolescents, especially adolescent girls, with an opportunity
      for relaying health recommendations.

PMID- 20136561
TI  - Where is the proof?

PMID- 20136562
TI  - Wearable health monitors: real-time, patient-friendly data collection.

PMID- 20136563
TI  - New frontiers: body works.

PMID- 20136565
TI  - After 50 years of ethinylestradiol, another oestrogen in combined oral
      contraceptives.

PMID- 20136566
TI  - Efficacy of contraceptive methods: A review of the literature.
AB  - OBJECTIVES: To provide a comprehensive and objective summary of contraceptive
      failure rates for a variety of methods based on a systematic review of the
      literature. METHODS: Medline and Embase were searched using the Ovid interface
      from January 1990 to February 2008, as well as the reference lists of published
      articles, to identify studies reporting contraceptive efficacy as a Pearl Index
      or life-table estimate. Reports that recruited less than 400 subjects per study
      group and those covering less than six cycles/six months were excluded. In
      addition, unlicensed products or those not internationally available, emergency
      contraception, and vasectomy studies were excluded. RESULTS: Information was
      identified and extracted from 139 studies. One-year Pearl Indices reported for
      short-acting user-dependent hormonal methods were generally less than 2.5. Gross
      life-table rates for long-acting hormonal methods (implants and the
      levonorgestrel releasing-intrauterine system [LNG-IUS]) generally ranged between
      0-0.6 per 100 at one year, but wider ranges (0.1-1.5 per 100) were observed for
      the copper intrauterine devices (0.1-1.4 per 100 for Cu-IUDs with surface area >
      or =300 mm( 2 ) and 0.6-1.5 per 100 for those with surface area <300 mm( 2 )).
      Barrier and natural methods were the least effective. CONCLUSIONS: Our review
      broadly confirms the hierarchy of contraceptive effectiveness in descending order
      as: (1) female sterilisation, long-acting hormonal contraceptives (LNG-IUS and
      implants); (2) Cu-IUDs with > or =300 mm( 2 ) surface area; (3) Cu-IUDs with <300
      mm( 2 ) surface area and short-acting hormonal contraceptives (injectables, oral
      contraceptives, the patch and vaginal ring), and (4) barrier methods and natural
      methods.

PMID- 20136567
TI  - Determining factors for condom use: A survey of young Italian adults.
AB  - OBJECTIVE: To identify factors that can hinder condom use in a sample of young
      adults. METHODS: The survey was carried out using a self-administered
      standardised anonymous questionnaire modified from the self-efficacy scale Condom
      Use Skill Measure. The questionnaire was administered to 1091 school-leavers who
      were attending a pre-university study course in August 2008 at Bari University,
      Italy. RESULTS: Of those interviewed, 88% had had sexual intercourse and the
      average age at the first experience was 16.8 years. The frequency of condom use
      at the most recent sexual intercourse was 52.6%. Non-condom use was associated
      with not having a condom immediately available, with problems in the partner
      accepting this particular barrier method, with the belief that proposing its use
      could lead to problems between the couple, with the assumption of not risking
      anything, with the fear that it causes irritation and with the belief that it
      does not feel natural. CONCLUSION: Our survey shows that there are opinions and
      attitudes held by young adults which hinder condom use. They should be a targeted
      by health education.

PMID- 20136568
TI  - Use of hormonal contraceptives in relation to antidepressant therapy: A
      nationwide population-based study.
AB  - OBJECTIVES: The relation between the use of different hormonal contraceptives and
      antidepressant therapy was investigated. METHODS: In a nationwide cross-sectional
      study among all women in Sweden aged 16-31, drug expenditure data on hormonal
      contraceptives and antidepressants were obtained from the Swedish Prescribed Drug
      Register. Odds ratios (ORs) for antidepressant use were calculated by logistic
      regression for progestin-only users versus non-users as well as for combined
      hormonal contraceptive (CHC) users versus non-users. RESULTS: In the study
      population (N = 917,993), 58.9% were hormonal contraceptive users, and 8.5% were
      antidepressant users. The age-pattern for antidepressant ORs differed between the
      two types of users of contraceptives; progestin-only users had significant ORs
      above 1 in all age groups whereas among CHC users the OR was above 1 solely in
      those aged 16-19. The largest difference between types of users was seen in the
      age group 16-19 in which women resorting to a progestin-only contraceptive had a
      67% (95% confidence interval: 57- 78%) higher antidepressant use than women
      treated with a CHC. CONCLUSION: Progestin-only contraceptive users resorted to
      antidepressants more than users of CHCs. This phenomenon is particularly
      pronounced among teenagers. Therefore, special attention should be given to young
      women's mental history when prescribing hormonal contraceptives and vice versa:
      the contraceptive history should be taken into account when prescribing
      antidepressants.

PMID- 20136569
TI  - Determinants of oral contraception use in a southern European setting.
AB  - OBJECTIVES: To describe the determinants of oral contraceptive (OC) use in
      Catalonia (Spain) in 2006. METHODS: More than 4,400 women, aged 15-49, were
      interviewed using a standardised health questionnaire. The main variable was OC
      use on any of the two days before the interview. Independent variables were socio
      economic class, marital status, number of children, visits to the gynaecologist,
      and lifestyles. The prevalence and the odds ratios of OC use were calculated.
      RESULTS: Around 17% of the women of reproductive age used OCs. The typical OC
      user was an affluent, nulliparous woman in her third decade, who had visited a
      gynaecologist during the preceding year. Being married was not related to OC use
      while having two children or more was negatively related. The use of OCs followed
      a curve that started during adolescence, reached a peak at age 24, decreased
      thereafter and flattened out after having reached a low point in the 30s.
      CONCLUSIONS: Results from this large sample of women confirm that OC use is lower
      in Spain than in many other European countries. The difference reflects divergent
      social and cultural attitudes toward fertility control, sexuality, and the roles
      of women in society, rather than problems with availability and accessibility.

PMID- 20136570
TI  - Seeing the ultrasound picture before an abortion.

PMID- 20136572
TI  - Effect of mtDNA mutation on tumor malignant degree in patients with prostate
      cancer.
AB  - OBJECTIVES: To understand mtDNA mutation frequency in patients with prostate
      cancer (Pca) and its effect on malignant degree of PCa. METHODS: A total of 130
      patients (mean age, 70.1 +/- 2.4; range, 58-97 years) undergoing either prostate
      biopsy or radical prostatectomy between October 2006 and March 2008 were
      included. Additionally, 61 patients with benign prostatic hyperplasia (mean age,
      69.9 +/- 1.1; range, 60-92 years) were included as a control group. The normal
      cells were isolated from each prostate cancer specimen by microdissection.
      Mitochondrial DNA (mtDNA4977) deletion mutations were identified by polymerase
      chain reaction. Gleason scores were determined by histopathology. RESULTS: Among
      the 130 Pca samples vs. 61 BPH samples, mtDNA4977 deletion mutation was detected
      in 98 cases (98/130, 75.4%) vs. in 9 cases (9/61, 14.7%) (P < 0.01, P = 0.001).
      There was a significantly higher prevalence of the mtDNA4977 deletion mutation in
      patients with prostate cancer compared to patients with BPH (P < 0.01). The
      incidence of the mtDNA4977 deletion in normal cells isolated from cancer specimen
      was 10.76% (14/130), which was significantly lower than that in prostate cancer
      group(P < 0.01). However, there was no significant difference versus BPH group (P
      > 0.5). Gleason scores were significantly higher in the group of patients with
      cancer with the mutation (7.6 +/- 2.4), compared to those without the mutation
      (6.2 +/- 1.1, P < 0.01). Logistic regression analysis demonstrated that Gleason
      scores (OR = 1.642, 95% CI: 1.232-2.183) and age (OR = 1.061, 95% CI: 1.041
      1.082) are both independent predictors of the mtDNA4977 deletion mutations.
      CONCLUSIONS: mtDNA4977 deletion mutation frequency may be useful as a biomarker
      in malignant degree appraisal in patients with Pca.

PMID- 20136573
TI  - Prevalence of cagA and vacA genotypes of Helicobacter pylori isolated from
      Turkish patients with active or non-active chronic gastritis.
AB  - Several virulence factors of Helicobacter pylori may contribute to gastric
      mucosal damage. In this study, the prevalence of cagA and vacA genotypes of H.
      pylori was examined in different patterns of chronic gastritis.
      Oesophagogastroendoscopy was performed in 147 dyspeptic patients. Antrum biopsies
      were obtained for isolation of H. pylori and for histopathological assessment. H.
      pylori vacAs1 and cagA genes were directly genotyped in the gastric biopsy
      specimens by polymerase chain reaction (PCR). A total of 102 dyspeptic patients,
      all H. pylori-positive by PCR, were included in the study. Of these, 59 had
      active chronic gastritis and 37 had non-active chronic gastritis. The prevalence
      of cagA and vacAs1 was higher among patients with active chronic gastritis than
      among those with non-active chronic gastritis (45.8% vs 21.6% (p = 0.02) and
      78.0% vs 40.5% (p < 0.001), respectively). In conclusion, both cagA and vacAs1
      genotypes are associated with the activity of chronic gastritis.

PMID- 20136575
TI  - A case of subcorneal pustular dermatosis in association with monoclonal IgA
      gammopathy successfully treated with acitretin.
AB  - Subcorneal pustular dermatosis (SPD), or Sneddon-Wilkinson disease, is a rare,
      chronic, recurrent, pustular eruption. Association with several diseases is well
      known, mainly IgA and IgG gammopathies or myelomas. Although dapsone is often
      considered to be the first-line treatment, some patients fail to respond or
      cannot tolerate the side effects. For cases that do not respond well to this
      treatment, acitretin, an excellent second-line treatment, may be used. Herein, a
      55-year-old woman with SPD associated with monoclonal IgA gammopathy refractory
      to dapsone is presented, who was successfully treated with acitretin in a short
      period.

PMID- 20136576
TI  - Genetic diversity of Aspergillus fumigatus in indoor hospital environments.
AB  - Environmental isolates of Aspergillus fumigatus are less studied than those
      recovered from clinical sources. In the present study, the genetic diversity
      among such environmental isolates was assessed, as well as their dispersion
      ability and the acquisition of new strains in 19 medical units of the same
      hospital. A. fumigatus isolates were genotyped using a single multiplex PCR-based
      reaction with eight microsatellite markers and an insertion/deletion
      polymorphism. A total of 130 unique genotypes were found among a total of 250 A.
      fumigatus isolates. Genotypic diversity ranged from 0.86 to 1 in samples from
      hospital rooms, and there was no correlation between these samples and the
      presence of high-efficiency particulate air filters or any other air filtration
      system. Four of the six most prevalent A. fumigatus strains were recovered from
      water samples. The occurrence of microvariation was common among environmental
      isolates, which affected each of the microsatellite markers. The assessment of
      the genetic diversity of A. fumigatus is a useful tool for illustrating the
      presence or absence of specific clonal populations in a clinical setting. A.
      fumigatus populations were highly dynamic indoors, and new populations were found
      in just a few months. Due to the high indoor dispersion capability of A.
      fumigatus, more attention should be given to strains with increased pathogenic
      potential or reduced susceptibility to anti-fungal drugs.

PMID- 20136577
TI  - How long does it take for the scientific literature to purge itself of fraudulent
      material?: the Breuning case revisited.
AB  - OBJECTIVE: It has been proposed that the scientific literature purges itself of
      articles known to be fraudulent. To test this, an investigation was carried out
      of post-retraction citations over a 19-year period in the Breuning case. METHODS:
      On 10 March 2008 a cited reference search was conducted (all languages, all
      document types) using the name 'Breuning SE*'. The time limit was 1989-2007 with
      an option to exclude self-citations. The search included the ISI Web of Science
      Database including the Science Citation Index Expanded, the Social Sciences
      Citations Index and the Arts & Humanities Citation Index. To ascertain the
      citation context, citations of Breuning were classified by two raters as
      affirmative, negative or neutral. FINDINGS: For the period 1989-2000 both
      negative and affirmative citations were found. For the period 2001-2006 only
      affirmative citations (even to retracted articles) were found, some in journals
      with higher impact factors than those citing the case as fraudulent. In spite of
      the small number of citations of Breuning's articles, it is alarming that the
      affirmative citing of fraudulent research has not completely ceased but continues
      24 years post-retraction (retracted 1982, cited 2006). While the limitations of a
      single case study are conceded, the results challenge the belief of scientific
      literature purging itself of fraudulent material. CONCLUSIONS: Retraction
      databases and widespread availability of computer software to check lists of
      references free of charge in any database or the internet are called for.
      Moreover, if a paper is never formally retracted, software for searching author
      names in the internet for fully investigated and proven scientific misconduct
      might be developed. The ethical guidelines on duplicate publication for purposes
      of disseminating the information as widely as possible should be reviewed.

PMID- 20136578
TI  - Renal function changes and NHS resource use in breast cancer patients with
      metastatic bone disease treated with IV zoledronic acid or oral ibandronic acid:
      a four-centre non-interventional study.
AB  - AIMS: To describe renal function monitoring practice in patients with metastatic
      bone disease (MBD) treated with IV zoledronic acid (ZA) and oral ibandronic acid
      (IA), the management pathways and NHS hospital resources used. METHODS: Medical
      records of 189 patients; IA (91), ZA (98) with primary breast cancer and MBD were
      reviewed, and data collected on renal monitoring and hospital visits during
      bisphosphonate therapy. Time and motion review of resources to administer the
      bisphosphonates was also conducted. RESULTS: Only 30% of patients given ZA and no
      patient given IA had baseline creatinine clearance (CrCl) recorded. Calculated
      baseline CrCl suggested impaired renal function in 33% ZA and 29% IA patients.
      Dose reductions were not made correctly in 29 ZA and 2 IA patients whose
      monitoring suggested it. ZA patients made more clinic and day care attendances
      than IA-treated patients, at twice the cost. Staff activity and patient time per
      visit was higher with ZA than IA. CONCLUSION: Although limited by retrospective
      design, these results demonstrate that in many patients, CrCl is not calculated
      before or during treatment with bisphosphonates. Renal function deteriorated in
      many patients during therapy. In view of these effects, practice should be
      reviewed to ensure appropriate dosing.

PMID- 20136579
TI  - Economic assessment of doripenem versus imipenem in the treatment of ventilator
      associated pneumonia.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP), the most common nosocomial
      infection in critically ill patients, is associated with significantly longer
      duration of mechanical ventilation, and increased mortality, hospital days, and
      health-care costs. A previously published prospective, randomized study
      established the noninferiority of intravenous (IV) doripenem versus IV
      imipenem/cilastatin ('imipenem') for VAP. This study compares the economic
      outcomes of IV therapy with doripenem versus imipenem as first-line treatment for
      VAP. METHODS: A decision-analytic model of inpatient care and outcomes for VAP
      was used to estimate costs associated with VAP treatment. The model calculates
      total hospital costs, comprising costs of initial and concomitant therapy, and
      costs associated with mechanical ventilation, intensive care unit stays, and
      total days in hospital. RESULTS: Total treatment costs for doripenem were $10,630
      lower than for imipenem ($71,259 vs. 81,889), driven primarily by differences in
      costs of mechanical ventilation ($45,224 for doripenem, $57,348 for imipenem).
      Probabilistic sensitivity analyses found doripenem consistently cost saving
      versus imipenem in 1,000 simulations. Study limitations include use of a simple
      model to represent a complex disease process and reliance on trial data that may
      not reflect real-world care and outcomes. CONCLUSIONS: Doripenem is a cost saving
      first-line treatment for VAP versus imipenem while providing an equivalent rate
      of cure.

PMID- 20136580
TI  - The cost-effectiveness of somatropin treatment for short children born small for
      gestational age (SGA) and children with growth hormone deficiency (GHD) in
      Sweden.
AB  - OBJECTIVE: Reduction in health-related quality of life is common in children born
      small for gestational age (SGA) or children with growth hormone deficiency (GHD).
      Growth hormone treatment with somatropin in these children leads to normalisation
      of height. The aim of this study was to determine whether somatropin is a cost
      effective treatment option for short children born SGA and GHD children in
      Sweden. METHODS: A Markov decision-tree model was used to calculate the relative
      costs and health benefits associated with somatropin treatment over the lifetime
      of SGA and GHD children, compared with no treatment. The analysis was undertaken
      from a Swedish Health Service perspective. As quality-adjusted life-year (QALY)
      data were not obtained directly in the clinical studies, a degree of uncertainty
      is related to these results. Sensitivity analyses assessed the degree of
      uncertainty surrounding central parameters. RESULTS: For short children born SGA,
      somatropin treatment was associated with an additional 3.29 QALYs at an
      incremental cost of 792,489 SEK (Swedish Krona), compared with no treatment. For
      GHD, somatropin treatment resulted in 3.25 additional QALYs at an incremental
      cost of 391,291 SEK. This equates to an incremental cost per QALY of 240,831 SEK
      and 120,494 SEK for SGA and GHD, respectively, below a cost-effectiveness
      threshold of 500,000-600,000 SEK/QALY. CONCLUSIONS: Somatropin is a cost
      effective treatment strategy in Sweden for children with GHD and SGA. To overcome
      present study limitations future clinical research should incorporate appropriate
      quality of life questionnaires.

PMID- 20136581
TI  - Suppression of type-I allergic responses by oral administration of grape marc
      fermented with Lactobacillus plantarum.
AB  - We investigated the inhibitory effects of fermented grape marc (FGM), lyophilized
      fine powder of skin, and seeds of Vitis vinifera Koshu grape prepared by
      fermentation with Lactobacillus plantarum, on type-I allergic responses in mice.
      Repeated oral administration of FGM, but not non-fermented grape marc (GM), to
      BALB/c mice primed with ovalbumin (OVA) resulted in a significant reduction of
      serum IgE levels, compared with those of immunized controls. After OVA challenge,
      increased numbers of eosinophils in bronchial alveolar lavage fluids (BALF)
      significantly decreased by treatment with FGM but not with GM. For passive
      cutaneous anaphylaxis (PCA) reaction, BALB/c mice received intradermal
      sensitization with anti-OVA IgE serum and were challenged intravenously with OVA
      containing Evans blue at 24 h after IgE sensitization. Oral administration of FGM
      at 30 min before OVA challenge significantly suppressed the PCA reaction. On the
      other hand, Lactobacillus alone and non-fermented GM did not show any suppressive
      effects. Interestingly, FGM samples prepared from grapes for red wine, such as
      Negroamaro (rich in resveratrol) or Tannat (rich in oligomeric procyanidin), did
      not suppress the reaction. These results indicate that oral administration of
      FGM, prepared from Koshu grape for white wine but not from grapes for red wine,
      could suppress both phases of type-I allergic responses. A fraction extractable
      with acetone was responsible for the suppressive effects of FGM.

PMID- 20136582
TI  - Effect of dodecylmaltoside (DDM) on uptake of BCS III compounds, tiludronate and
      cromolyn, in Caco-2 cells and rat intestine model.
AB  - The efficacy of n-lauryl-beta-D-maltopyranoside, (dodecylmaltoside, DDM) as a
      permeability-enhancer for tiludronate and cromolyn (BCS Class III, water-soluble
      compounds with oral bioavailability < 5%) was evaluated in Caco-2 cell monolayers
      and rat intestinal sacs. In Caco-2 cells samples were collected over a 5-h period
      and transepithelial resistance (TEER) was measured concurrently. In rat
      intestinal sacs, samples of the test compounds and marker (Lucifer Yellow) were
      collected over a 40 min period; accumulation in the serosal fluid and intestinal
      tissue was measured. At lower concentration DDM had no effect on cromolyn
      permeability and a marginal increase was observed at higher concentration.
      Tiludronate permeability in the presence of DDM showed greater enhancement as
      compared to cromolyn. At higher concentration DDM appeared to cause permanent
      damage to the cell monolayer (irreversible change in TEER). In the intestinal
      tissue, DDM caused increased tissue accumulation of test compounds. This
      indicated that transport was not restricted to the paracellular route and damage
      to the intestinal tissue could not be ruled out. Based on the results obtained in
      this study it can be concluded that at concentrations that are non-toxic DDM
      appears to have a limited use to improve the oral absorption of cromolyn and
      tiludronate.

PMID- 20136583
TI  - Irritable bowel syndrome and disease severity: are we undertreating our patients?

PMID- 20136584
TI  - Antidepressants in functional dyspepsia.

PMID- 20136586
TI  - Alosetron for severe diarrhea-predominant irritable bowel syndrome: safety and
      efficacy in perspective.
AB  - Irritable bowel syndrome affects 5-10% of North Americans, with an estimated one
      third having a diarrhea-predominant form. Alosetron hydrochloride (Lotronex) is a
      serotonin receptor type 3 antagonist approved in early 2000 for use in women with
      diarrhea-predominant irritable bowel syndrome (IBS-D). Initial use was
      widespread, but infrequent serious adverse events of ischemic colitis and severe
      constipation-related complications prompted alosetron's voluntary withdrawal from
      the US market in November 2000. Unprecedented public request prompted its
      reintroduction in 2002 under a Risk Management Plan, including a more restricted
      indication and a Prescribing Program for Lotronex. Despite these measures, the
      use of alosetron has been very limited since its reintroduction. Possible
      deterrents to its use include concerns over safety and the possible medical-legal
      implications raised by the Risk Management Plan. It is also possible that changes
      in the natural history and/or diagnosis of IBS-D have reduced the target
      population. Given the unique regulatory history of alosetron, these issues
      continue to engender controversy. This article profiles these concerns and
      reviews the pharmacology, clinical efficacy and safety, and post-marketing
      experience with alosetron. Myths and misconceptions related to alosetron use, or
      lack thereof, are addressed to provide the reader with the evidence needed to
      make informed treatment decisions for their female patients with severe IBS-D.

PMID- 20136587
TI  - Old and new serological tests for celiac disease screening.
AB  - Evaluation of: Lewis NR, Scott BB. Meta-analysis: deamidated gliadin peptide
      (DGP) antibody and tissue transglutaminase (tTG) antibody compared as screening
      test for celiac disease. Aliment. Pharmacol. Ther. 31(1), 73-81 (2010). In celiac
      disease (CD), deamidation of gliadin peptides, induced by tissue transglutaminase
      (tTG), generates novel antigenic epitopes evoking a specific immune response.
      Serological tests based on the detection of antibodies to deamidated gliadin
      peptides (DGP) have been developed with very promising results in terms of
      sensitivity and specificity for CD screening. In the present study, a meta
      analysis of studies published from 1998 to 2008 was designed to compare the
      performance of DGP antibodies with that of tTG antibodies, the validated and
      routinely employed test for CD screening. The authors have limited their analysis
      to IgA class antibodies underlining that most of the considered studies had
      methodological imperfections, especially ascertainment bias. The results of this
      meta-analysis indicated that the pooled sensitivities for DGP and tTG antibodies
      were 87.8% (95% CI: 85.6-89.9) and 93% (95% CI: 91.2-94.5), respectively, and the
      pooled specificities were 94.1% (95%CI: 92.5-95.5) and 96.5% (95% CI: 95.2-97.5),
      respectively. In summary, although both tests represent a very good tool for
      identifying celiac patients, tTG antibodies display a higher predictive value
      than DGP antibodies, and must still be considered the best serological test for
      CD screening.

PMID- 20136588
TI  - End points of therapy in chronic hepatitis B.
AB  - This review assesses the relevance of the clinical, histological, biochemical and
      virological end points in the course and outcome of chronic hepatitis B. The
      pathway and the impact of the variation in these end points are presented, as
      well as their definitions. The treatment goals are discussed in terms of quality
      of life and survival. Prevention of the progression of the disease to cirrhosis,
      decompensated cirrhosis, end-stage liver disease and hepatocellular carcinoma
      seems to be the best approach to improve survival. As these criteria are long
      term end points, easier to use end points assessed in clinical trials as efficacy
      objectives were also analyzed to determine whether they can be used as accurate
      surrogate criteria. Results of therapy were then analyzed according to the
      approved end points and in terms of management of chronic hepatitis B. Finally,
      an attempt to define new clinical end points is discussed in view of the
      development of more potent antiviral strategies.

PMID- 20136589
TI  - Treatment of hepatitis C in children.
AB  - Hepatitis C affects 4-10% of children born to infected mothers, and 80% of them
      develop chronic infection. Most patients with chronic hepatitis C virus infection
      are asymptomatic, with persistent or intermittent biochemical abnormalities.
      Severe liver disease may develop 10 years after onset of infection, with a less
      than 2% overall risk during the pediatric age. Available therapies have no
      contraindication in children if otherwise healthy. The US FDA and EMEA have
      recently approved combined pegylated-IFN-alpha 2b plus ribavirin treatment for
      children, who should be over 3 years of age in order to avoid severe side
      effects. Experiences in pilot trials and international studies indicate a
      response rate of 50% in genotype 1 patients, and more than 90% in genotype 2 or 3
      patients, indicating resolution of chronic disease.

PMID- 20136590
TI  - Know your enemy: translating insights about the molecular biology of hepatitis C
      virus into novel therapeutic approaches.
AB  - Identified in 1989 as the cause of what was then known as hepatitis non-A non-B,
      the hepatitis C virus (HCV) continues to be a significant global public health
      threat, given that an estimated 123 million individuals are chronically infected
      and, thus, at risk for cirrhosis and hepatocellular carcinoma. After 20 years of
      basic and clinical research into HCV infection, the backbone of therapy has
      remained interferon, a drug that - in a different formulation - was already being
      employed before HCV was even identified. Nonetheless, research has overcome many
      obstacles that stood in the way of studying this pre-eminent human pathogen. Hard
      won insights into its molecular biology have identified promising therapeutic
      targets, and we are now on the verge of an era where rationally designed
      therapeutics, also referred to as specifically targeted antiviral therapy for
      HCV, will reshape the treatment of hepatitis C. This article describes recent
      insights on the molecular biology of HCV and the efforts to translate them into
      clinical applications.

PMID- 20136591
TI  - Joint involvement in inflammatory bowel disease: managing inflammation outside
      the digestive system.
AB  - Joint inflammation is present in approximately 30% of patients with inflammatory
      bowel disease. Peripheral arthritis can frequently be controlled by an optimal
      treatment of the gut inflammation in association with short-term use of NSAIDs.
      Recurrent inflammation requires the use of sulfasalazine. More therapy-resistant
      forms and axial arthropathy can be treated with anti-TNF drugs, predominantly
      infliximab and adalimumab. An intensified multidisciplinary approach in research
      and in the clinic may help to unravel the question of why common etiopathogenic
      mechanisms ultimately lead to different disease phenotypes. Animal models may
      help to identify the most promising therapeutic strategies including in the near
      future modulation of adhesion molecules, costimulatory molecules and the Th17
      pathway.

PMID- 20136592
TI  - Minimally invasive esophagectomy: an overview.
AB  - Minimally invasive approaches to esophageal resection have been shown to be
      feasible and safe, with outcomes similar to open esophagectomy. There are no
      controlled trials comparing the outcomes of minimally invasive esophagectomy
      (MIE) with open techniques, just a few comparative studies and many single
      institution series from which assessment of MIE and its present role have been
      made. The reported improvements from MIE approaches include reduced blood loss,
      time in intensive care and time in hospital. In comparative studies there is no
      clear reduction in respiratory complications, although larger series suggest
      there may be a benefit from MIE. Although MIE approaches report less lymph node
      retrieval compared with open extended lymphadenectomy, MIE cancer outcomes are
      comparable with open surgery. MIE will be a major component of the future
      esophageal surgeons' armamentarium, but should continue to be carefully assessed.
      There is a role for multicentered studies to prospectively audit outcomes. Large
      numbers of patients would be required to perform randomized trials of MIE versus
      open resection.

PMID- 20136593
TI  - Sleeve gastrectomy: a new surgical approach for morbid obesity.
AB  - While obesity and morbid obesity have reached epidemic proportions worldwide,
      bariatric surgeons continue to develop safer and more efficacious procedures to
      battle this lethal disease. Sleeve gastrectomy, a relative new surgical approach,
      was initially conceived as a restrictive component of the biliopancreatic
      diversion and duodenal switch in the era of open bariatric surgery. With the
      advent of minimally invasive surgery in the late 1980s, laparoscopic sleeve
      gastrectomy (LSG) has been proposed as a step procedure in high-risk patients,
      followed by a second step Roux-en-Y gastric bypass or biliopancreatic diversion
      and duodenal switch and, recently, as a standalone bariatric approach. This
      article reviews the literature and reports the results achieved with LSG
      performed either as the initial operation for high-risk, high body mass index
      patients followed by a definitive weight loss operation, or used as a final
      viable alternative to other well-established bariatric procedures. An extensive
      literature review was conducted and the information currently available
      surrounding LSG, such as history, indications and contraindications, mechanism of
      weight loss, technique and outcomes and controversial issues are discussed. LSG
      is an accepted procedure for the surgical management of morbid obesity. It is
      gaining popularity as a primary, staged and revisional operation for its proven
      safety and simplicity, as well as short-term and mid-term efficacy. Excess weight
      loss and remission of comorbidities have been reported to take place in a
      frequency comparable with other well-established procedures. Despite all of the
      above-mentioned factors, long-term results and larger series are pending.

PMID- 20136595
TI  - Release of tetracycline from O-carboxymethylchitosan films.
AB  - O-carboxymethylchitosan films containing tetracycline were prepared by the
      casting method. The films were hardened by reaction with glutaraldehyde-induced
      crosslinking and heat treatment at 90 degrees C, 120 degrees C and 150 degrees C.
      The effect, on the films, of hardening methods, water uptake, moisture, drug
      release and antimicrobial activity against Staphylococcus aureus was evaluated.
      The O-carboxymethylchitosan films were soluble in simulated saliva and after
      treatment, and the water uptake of the films decreased as the temperature or
      presence of glutaraldehyde increased. The antimicrobial activity of tetracycline
      was preserved, and efficiency was dependent on the hardening treatment to which
      the films were submitted.

PMID- 20136596
TI  - Intracellular redox compartments: mechanisms and significances.
AB  - With the appearance of oxygen and the development of aerobic life on earth,
      reactive oxygen species (ROS) became important factors influencing a number of
      processes within a cell. Although initially considered unwanted and harmful by
      products of a number of cellular reactions, the last decade has shown that ROS
      can also act as signalling molecules mediating changes in O(2) tension, as well
      as the response to hormones, growth factors, and mechanical or chemical stress.
      Different ROS-generating and ROS-degrading systems in different intracellular
      compartments seem to play an important role. In line with this, it appears that
      proteins already well known for an ROS-unrelated specific function in one
      compartment participate in the ROS response within another compartment. Thus, it
      is easy to envision that redox changes in different compartments and resulting
      changes in ROS levels may represent an important mechanism of intracellular
      communication between different cellular compartments.

PMID- 20136597
TI  - Cardiac arrhythmias in congestive heart failure.

PMID- 20136598
TI  - Cardiovascular disease in women.

PMID- 20136599
TI  - Influenza and myocardial infarction.

PMID- 20136601
TI  - Mechanism of action and clinical development of ticagrelor, a novel platelet ADP
      P2Y12 receptor antagonist.
AB  - Inhibition of the platelet ADP P2Y(12) receptor has shown to be associated with a
      marked risk reduction of atherothrombotic events in high-risk settings, including
      patients with acute coronary syndromes and those undergoing percutaneous coronary
      interventions. Clinical and laboratory experiences have led to a better
      comprehension of the drawbacks of currently available P2Y(12) receptor
      antagonists, stimulating the development of novel agents. Ticagrelor (AZD6140) is
      the first drug of a new chemical class called cyclopentyltriazolopyrimidine,
      which is administered orally and has a reversible P2Y(12) receptor inhibitory
      effect. Preclinical and early-phase clinical studies have shown ticagrelor to be
      characterized by a rapid, greater and consistent antiplatelet effect with a
      favorable safety profile. Recent findings from large-scale Phase III trials
      showed ticagrelor to be more effective in preventing ischemic events in acute
      coronary syndrome patients without an increased risk of protocol-defined major
      bleeding, but with an increase in the rate of nonprocedure-related bleeding,
      compared with currently recommended treatment regimens. This article provides an
      overview of the pharmacologic properties and clinical development of ticagrelor.

PMID- 20136602
TI  - Efficacy and safety of nesiritide in patients with acute decompensated heart
      failure.
AB  - Acute decompensated heart failure is a common clinical problem with associated
      poor outcomes. Over the last decade, attention to this area has greatly
      increased, with a focus on medical therapies that may safely offer improvement in
      acute symptoms and early outcomes. Previous therapies that focused on increased
      inotropy have generally failed to improve symptoms without adverse consequences.
      Thus, attention towards vasodilators and natriuretic peptides, such as
      nesiritide, has increased owing to nesiritide's symptomatic improvement and
      unique mechanism of improvement in hemodynamics. However, the pathophysiology of
      acute decompensated heart failure is complex and the impact of nesiritide on
      important clinical end points, beyond symptomatic and hemodynamic improvement, is
      unknown.

PMID- 20136603
TI  - In the wireless era: leadless pacing.
AB  - Cardiac pacemakers have been the standard therapy for patients with
      bradyarrhythmias for several decades. The pacing lead is an integral part of the
      system that serves as a conduit for the delivery of energy pulses to stimulate
      the myocardium. However, it is also an Achilles tendon that directly causes most
      device complications both acutely during implant and chronically years
      afterwards. Both durability and optimization of the stimulation site are
      important areas of improvement for manufacturers and implanters. Elimination of
      the pacing lead and the utilization of other means for energy transfer is the
      only way to avoid lead complications and allow a better choice of stimulation
      site. Leadless pacing with ultrasound-mediated energy has been demonstrated in
      animals and humans in acute studies. This has aroused intense interest in the
      field of cardiac pacing. With concerted effort from the profession and the
      industry, leadless pacing may indeed become a realizable concept.

PMID- 20136604
TI  - Cardiovascular disease is preventable among women.
AB  - Coronary heart disease (CHD) among women is preventable. Women with minimal
      cardiovascular risk factors and low coronary calcium scores have a very low
      incidence and mortality due to CHD. Women have much less coronary atherosclerosis
      than men, especially those of younger age groups. The lower coronary
      atherosclerosis is likely a function of both lower risk factors premenopausal and
      the effects of estrogen on the arterial wall. Reduction of elevated risk factors,
      such as atherogenic lipoproteins, systolic blood pressure and smoking cessation,
      results in substantial reduction in the risk of CHD for both men and women. There
      is relatively little evidence that these effects are different for men as
      compared with women. The prevention of increase in risk factors premenopausal
      (primordial prevention) by public health initiatives, individualized lifestyle
      intervention and more aggressive pharmacological therapies for most
      postmenopausal women to prevent the development and progression of
      atherosclerosis and thrombosis are the cornerstone of CHD prevention for women
      and will have the greatest impact on women's cardiovascular health, improving
      quality of life, decreasing healthcare costs for CHD and substantially decreasing
      health disparities.

PMID- 20136605
TI  - Clinical assessment of arrhythmias in tetralogy of Fallot.
AB  - As a major success story of an early surgical era, corrective surgery transformed
      the prognosis of patients born with tetralogy of Fallot. With lifelong care,
      healthy survival well into adulthood is now the norm, albeit somewhat blemished
      by long-term sequelae. Arrhythmias are an important source of morbidity and a
      leading cause of mortality. This succinct review provides a contemporary summary
      of the prevalence and types of arrhythmias encountered in tetralogy of Fallot,
      including conduction disorders, atrial and ventricular tachyarrhythmias, and
      sudden death. Current prognostic markers and existing diagnostic tools are
      discussed, and available therapeutic options are elaborated.

PMID- 20136606
TI  - Effectiveness of blood pressure lowering: evidence-based comparisons between men
      and women.
AB  - The global burden of blood pressure-related disease is escalating faster among
      women than among men and, in recent years, age-adjusted mortality rates among
      women have actually increased. This has led to the speculation that there might
      be major sex-specific differences in the effectiveness of preventive therapies
      such as blood pressure-lowering drugs. However, large overviews of both
      observational and clinical trial data provide strong evidence that the protection
      against serious vascular events afforded by blood pressure reduction using a
      range of commonly used drugs is comparable for men and women. Underestimation of
      cardiovascular risk and supoptimal therapy are more likely to account for poorer
      outcomes among women. These differences highlight the importance of global
      initiatives such as 'Go Red for Women'.

PMID- 20136607
TI  - Venous thromboembolism in women taking hormonal contraceptives.
AB  - Hormonal contraceptives are a popular method of contraception, but their use has
      been associated with an increased risk for venous thromboembolism. In order to
      reduce such risk, these compounds have been changed in their dosage, chemical
      composition and route of administration. The absolute risk of death from
      pulmonary embolism in contraceptive users has been estimated to be 10.5 (95% CI:
      6.2-16.6) per million woman-years. The safest option is an oral contraceptive
      containing levonorgestrel combined with a low dose of estrogen. Identifying women
      at increased risk for venous thromboembolism is difficult, and greater use of
      thromboprophylaxis during immobility or minor surgery should be warranted.
      Several authors have called for all women to be screened for thrombophilia before
      prescription of hormonal contraceptives, but its cost-effectiveness remains
      uncertain.

PMID- 20136608
TI  - So many definitions of heart failure: are they all universally valid? A critical
      appraisal.
AB  - Defining heart failure (HF) is a matter of finding the most appropriate words to
      formulate the definiens for HF that will be universally applicable in all
      specific circumstances pertaining to the nature of HF. Currently available
      definitions of HF contain ambiguities and notable deficiencies such that non
      heart failure medical conditions can become mislabelled as heart failure.
      Principles of how best to formulate definitions have been employed to provide a
      guide on how to appraise published definitions of HF. A fundamental requirement
      of a good definition is that it should be universal, and by this criterion, we
      need to question the validity of a conventional dogma that a collection of
      clinical diagnostic features are equivalent to HF definitions. A long-standing
      deficiency in HF definitions is the inability to take into account the
      quantifiable extent of functional impairment of the heart. Other traditional
      misconceptions surrounding HF definitions have also been addressed. In line with
      Derek Gibson's proposal, we have rephrased William Harvey's description of the
      cardiac role in maintaining the circulation in terms of Newtonian physics and of
      the Law of Conservation of Energy to reach a more universal and less ambiguous
      definition of HF, with the objective of advancing the science of HF and the
      treatment of this distressing condition.

PMID- 20136609
TI  - Cardiac resynchronization therapy for the treatment of heart failure.
AB  - Heart failure is posing an increasing burden on healthcare systems around the
      world, a consequence of increased survival from acute coronary syndromes and life
      prolonging medications. Cardiac resynchronization therapy has become a ratified
      and established therapy for heart failure to reduce both the morbidity and
      mortality of the condition. Its prophylactic role in patients who have minimal
      symptoms to delay future deterioration is a novel development. The indications
      for this therapy continue to evolve, mainly as a result of company-sponsored
      multicenter trial data aimed at broadening its usage. Uncertainty remains on how
      to accurately identify individuals who will respond to resynchronization therapy
      and how best to manage patients following device implant.

PMID- 20136610
TI  - Current and future therapy for pulmonary hypertension in patients with right and
      left heart failure.
AB  - Pulmonary hypertension (PH) is a devastating condition that without proper
      management can deteriorate progressively. Elevated pulmonary artery pressure
      without an identifiable etiology is called IPAH. PH resulting from a specific
      disease is referred to as secondary PH; left-sided cardiac disease can lead to an
      increase in pulmonary artery pressure resulting in increased vascular resistance
      and subsequent structural remodeling. If left-sided failure progresses to right
      sided failure with high pulmonary artery pressure, the outcome is ominous. It has
      been clearly proven that early diagnosis and effective medical therapy can
      markedly decrease morbidity and mortality. In this review, we discuss the current
      treatment modalities and their limitations for PH secondary to heart failure.
      Conventional therapy in patients with pulmonary arterial hypertension as well as
      recent advances in the medical management of PH in general, are also described.
      Last, the surgical management of these patients and other promising
      interventional modalities are reviewed.

PMID- 20136611
TI  - Systolic and diastolic left ventricular dysfunction: from risk factors to overt
      heart failure.
AB  - Because life expectancy and the prevalence of risk factors such as hypertension,
      obesity and diabetes are rising globally, heart failure (HF) is growing into a
      major health problem. Impairment of left ventricular (LV) diastolic function as
      well as systolic function appear very early in the course of heart disease.
      Recent HF guidelines, therefore, place special emphasis on the detection of
      subclinical LV dysfunction and the timely identification of risk factors for HF.
      Conventional echocardiography combined with new imaging techniques such as tissue
      Doppler and tissue tracking are sensitive tools to detect early subclinical
      deterioration of LV function. Community-based studies revealed a higher
      prevalence of LV systolic and diastolic dysfunction using the new
      echocardiographic imaging techniques. Future prospective studies will clarify the
      hitherto unknown prognosis associated with early symptom-free LV dysfunction.

PMID- 20136612
TI  - Management of aortic valve disease in the presence of left ventricular
      dysfunction.
AB  - The development of heart failure in patients with aortic valve disease is
      associated with increased mortality, unless aortic valve replacement is
      performed. There is an especially high risk of death among patients with low
      ejection fraction. The heart failure must be treated and the patient's condition
      stabilized before surgery is performed. A delay in surgery, on the other hand,
      may lead to irreversible cardiac dysfunction and culminate in heart failure.
      Initial management must include an evaluation of the severity of the lesion and
      the functional state of the left ventricle. It is possible to achieve both of
      these goals simultaneously with echocardiography and pharmacologic challenge.

PMID- 20136613
TI  - Magnetic resonance spectroscopy in myocardial disease.
AB  - 31-phosphorous ((31)P) magnetic resonance spectroscopy (MRS) is a technique that
      allows the noninvasive characterization of the biochemical and metabolic state of
      the myocardium in vivo. MRS is a pure form of molecular imaging using magnetic
      resonance signals from nuclei with nuclear spin to assess cardiac metabolism
      without the need for external radioactive tracers. (31)P MRS provides information
      on the underlying metabolic abnormalities that are fundamental to common
      conditions including ischemic heart disease, cardiomyopathy, hypertrophy and
      valvular disease. (31)P MRS could potentially also have a role to play in
      assessing response to therapy as well as the effectiveness of metabolic
      modulating agents. However, the use of MRS is currently limited to research due
      to its poor reproducibility, low spatial and temporal resolution, and long
      acquisition times. With technical advances in both the spectrometers and
      postprocessing, MRS is likely to play a role in the future of multimodal
      noninvasive cardiac assessment.

PMID- 20136614
TI  - Current treatment of heart failure in the USA.
AB  - Among elderly adults, the most common reason for hospitalization is heart
      failure. Understanding the treatment options for this complex syndrome is vital
      to the practice of contemporary medicine. Early recognition of patients at risk
      for developing heart failure and the stage-appropriate management of patients
      with established heart failure is paramount for optimal patient care. However,
      the vast array of therapeutic options currently available can seem daunting. It
      is the aim of this review to describe the framework for approaching heart failure
      patients so that the physician can provide the most appropriate therapies at each
      stage of the disease.

PMID- 20136615
TI  - New insights on fetal ductal constriction: role of maternal ingestion of
      polyphenol-rich foods.
AB  - Fetal ductus arteriosus constriction is a clinical disorder that occurs as a
      result of inhibition of the prostaglandin synthesis pathway, and has long been
      associated to maternal intake of nonsteroidal antiinflammatory drugs in late
      pregnancy. As a consequence of an increased right ventricular pressure, with
      tricuspid regurgitation and heart failure, there is a risk for the development of
      neonatal pulmonary artery hypertension. This article reviews the basic knowledge
      of the mechanisms involved in this important disorder. Clinical and experimental
      evidence that maternal consumption of polyphenol-rich substances, such as herbal
      teas, orange and grape juice, chocolate, and others, may interfere with fetal
      ductus arteriosus dynamics are discussed. Preventive measures to avoid fetal
      ductal constriction in the third trimester of pregnancy are discussed, including
      the possible need to change maternal dietary orientation, aiming to limit
      ingestion of foods with high concentrations of polyphenol-rich substances.

PMID- 20136617
TI  - Increase effect of transforming growth factor on eotaxin production by normal
      cultured dermal fibroblasts stimulated with interleukin-4: inhibitory effect of
      suplatast tosilate on eotaxin production.
AB  - Eotaxin plays a central role in the development of allergic disease, including
      atopic dermatitis, asthma, and nasal allergy. Interleukin (IL)-4 induces eotaxin
      production in normal human dermal fibroblasts. On the other hands, Transforming
      growth factor-beta (TGF-beta), a multifunctional regulatory cytokine, affects
      many biological functions, including fibroblast growth and differentiation and
      Th2 cytokine regulation. In this study, we investigated the effect of TGF-beta on
      IL-4-induced eotaxin production by normal human fibroblasts, as well as the
      effect of suplatast tosilate, an antiallergic drug that selectively inhibits Th2
      cytokine production. Dermal fibroblast treatment with IL-4 and TGF-beta for 24 h
      increased eotaxin production and expression of eotaxin mRNA, as measured by
      enzyme-linked immunosorbent assay (ELISA) and reverse-transcriptase polymerase
      chain reaction (RT-PCR), respectively. TGF-beta synergistically up-regulated
      eotaxin production and eotaxin mRNA expression when stimulated with IL-4.
      Suplatast tosilate dose-dependently inhibited eotaxin production induced by IL-4
      or IL-4 plus TGF-beta. These results suggest that TGF-beta may regulate skin
      allergic inflammation by up-regulating eotaxin production in dermal fibroblasts.
      Suplatast tosilate might suppress this inflammation by inhibiting eotaxin
      production.

PMID- 20136618
TI  - Identification of HLA-A24-binding peptides of Mycobacterium tuberculosis derived
      proteins with beta 2m linked HLA-A24 single chain expressing cells.
AB  - Tuberculosis is caused by an intracellular pathogen Mycobacterium tuberculosis
      (Mtb) and poses a persistent threat to global health. MHC class I-restricted CD8
      cytotoxic T lymphocytes (CTL) are essential for protective immunity to
      Tuberculosis. Information for CTL epitopes derived from Mtb is desirable for
      vaccine design and assessment of T cell responses. However, the knowledge about
      CTL epitopes of Mtb, particularly those non-A2 HLA alleles restricted is rare. In
      this study, beta-2-microglobulin (beta 2m, beta(2)m) linked HLA-A24 single chain
      was expressed on RMA-S cell line defective in the endogenous antigen processing
      and applied for screening of peptides which could stabilize the HLA-A24 complex
      on the cell surface. From a group of peptides predicted as binders by a computer
      algorithm, five peptides were shown to bind to HLA-A24 protein on the cell
      surface. As comparison we have also identified a dozen Mtb proteins derived
      peptides that bind to HLA-A2 specifically. The cell line and HLA binders present
      here would be useful for further identification of CD8 restricted Mtb epitopes.

PMID- 20136619
TI  - Production and characterization of monoclonal antibodies against the
      extracellular domain of CA 125.
AB  - Carcinoma antigen 125 (CA 125) is overexpressed in ovarian cancer and antibodies
      against it are widely employed for diagnostic purposes. The rarity of CA 125
      antigenic domains and its highly glycosylated structure, however, is a problem
      that may prevent immunized mice from developing a diversified population of anti
      CA 125 antibodies. In this study a prime-boost strategy, which potentially could
      augment the humoral immune responses against rare and poorly immunogenic
      determinants, was used for immunization of mice and monoclonal antibodies (mAbs)
      were produced by hybridoma technology. Reactivity of mAbs was then assessed by
      ELISA, western blotting, immunoprecipitation, immunohistochemistry and
      immunofluorescence staining of OVCAR-3 cell line. Altogether, 10 clones were
      produced, 3 of which had IgG isotype and the rest were IgM. Two-third of clones
      recognized cognate antigen in fixed and living cells and had strong
      immunoreactivity in IHC staining. In Western blotting, our antibodies recognized
      CA 125 as high molecular weight antigen mostly migrated in the 3% stacking gel.
      Immunoprecipitation of OVCAR-3 cell lysate by mAbs resulted in a very similar
      migration pattern that reconfirmed their specificities. The mAbs produced in this
      study are invaluable tools in diagnosis and research fields for assessment of CA
      125 expression in cancerous ovarian tissues.

PMID- 20136620
TI  - Adjuvant properties of AcF1, an immunostimulant fraction of Alchornea cordifolia
      extract.
AB  - As a result of strong experimental data supporting effectiveness and safety, herb
      based immunomodulators are paving way as alternative sources of potent adjuvants
      for vaccines. In this study, the immunostimulatory and adjuvant properties of
      AcF1, a flavonoids-rich fraction of Alchornea cordifolia extract, was evaluated.
      In vitro, AcF1 was shown to activate total splenocytes, CD4+ T cells, and B
      cells, inducing remarkable increases in CD69 expression, profound proliferation,
      and increased IL-4 and IFN-gamma expression by the naive splenic cells in a
      concentration-dependent manner. Lympho-activation and proliferation induced by
      AcF1 was partially inhibited by U0126, a selective mitogen activated protein
      kinase kinase (MKK) inhibitor. Additionally, AcF1 was shown to induce structural
      and functional maturation of bone marrow-derived dendritic cells (BM-DCs) and
      their specific-antigen presentation functions. Used as an adjuvant in a
      homologous prime-boost OVA immunisation in C57BL/6 mice, AcF1 significantly
      (P<0.05) increased the level of OVA-specific antibody titres in the sera of
      immunised mice, compared to the control group immunised with OVA alone. The
      results of this study show AcF1 as a potent immunostimulant and a potential
      adjuvant for further study in combination with other vaccine antigens.

PMID- 20136621
TI  - Inhibitory effect of Agrimonia pilosa Ledeb. on inflammation by suppression of
      iNOS and ROS production.
AB  - Herbal medicines including Agrimonia pilosa Ledeb. (APL) have been traditionally
      used to treat inflammations including allergic disease as valuable medicinal
      properties. To investigate the attenuating ability of APL on inflammation, the NO
      release and ROS production, which play a key role in inflammatory and immune
      responses, was first tested using in vitro assay. The 80% ethanol extract of APL
      showed a significant activity to inhibit NO release and ROS production. In
      additional extracts from 80% ethanol extract of APL, n-butanol (BuOH) extract
      displayed the most potent anti-inflammatory effects based on in vitro assay. The
      extract also significantly reduced nitric oxide in lipopolysaccharide-activated
      RAW 264.7 macrophage cells (p < 0.05), and suppressed the nitric oxide synthase
      (iNOS) expression, whereas the extract showed no inhibitory effect on
      cyclooxygenase-2 (COX-2) expression, suggesting that the BuOH extract of APL
      could reduce the NO production through suppression of iNOS, but not COX-2. The
      BuOH extract also showed a significant effect in a carrageenan-induced rat paw
      edema in vivo model, consistent with our in vitro results. Our findings suggest
      that the BuOH extract of APL shows a potential anti-inflammatory activity,
      substantiating its traditional use in medicine.

PMID- 20136622
TI  - Phytoglycoprotein (75 kDa) suppresses release of histamine and expression of IL-4
      and IFN- gamma in BPA-treated RBL-2H3 cells.
AB  - The current study investigated whether the phytoglycoprotein (75 kDa) isolated
      from Cudrania tricuspidata Bureau (CTB glycoprotein) has anti-allergic
      inflammatory potential. Bisphenol A (BPA) is well known to promote development of
      allergy-related immune dysfunction. This experiment evaluated the release of
      histamine, increased intracellular Ca(2+) level, and the activities of protein
      kinase C alpha (PKC alpha), transcription factors NFkappaB and cytokines (IL-4,
      and IFN-gamma) in BPA-treated RBL-2H3 cells. The results in this study showed
      that the phytoglycoprotein (75 kDa) inhibits the intracellular Ca(2+) level,
      translocation of PKC alpha from cytosol to membrane and the translocation of NF
      kappaB in cells. We also found that the phytoglycoprotein (75 kDa) inhibits the
      release of histamine, and the expressions of cytokines (IL-4 and IFN-gamma) in
      the presence of BPA in RBL-2H3 cells. The results obtained from these experiments
      indicated that the phytoglycoprotein (75 kDa) inhibits release of histamine and
      expressions of IL-4, and IFN-gamma via down regulations of Ca(2+)/PKCalpha and NF
      kappaB on the stage of degranulation induced by BPA. From point of view, we
      speculated that the phytoglycoprotein (75 kDa) is one of natural compounds that
      can block allergic-inflammation caused by BPA.

PMID- 20136624
TI  - Diagnostic accuracy of different immunological methods for the detection of
      antineuronal antibodies in paraneoplastic neurological syndromes.
AB  - The aim of this work was to evaluate the diagnostic accuracy of three different
      analytical methods for the detection of antineuronal antibodies and outline how
      they might be used to diagnose Paraneoplastic Neurological Syndromes (PNS) in a
      more effectively and rationally way. One hundred and four patients with
      neurological diseases were studied: 38 with paraneoplastic neurological disorder,
      44 with other neurological diseases, and 22 with systemic autoimmune diseases and
      neurological disorders. 20 healthy subjects and 18 subjects with tumour without
      neurological disorders were also studied. Antineuronal antibodies were tested
      using three methods: Western blot (WB); Line-blot (LB); and indirect
      immunofluorescence (IIF) on primate cerebellum. The diagnostic sensitivity of the
      IIF, WB and LB methods was 28.9%, 26.3% and 36.8%, respectively, and their
      specificity was 95.2%, 97.1% and 98.1% respectively. The combined use of the
      three methods brought the sensitivity to 39.4%. The results of this study show
      that the methods used in clinical laboratories for the detection of antineuronal
      antibodies have good specificity. Among the three methods assessed, LB showed the
      highest diagnostic accuracy and also allowed for recognition of fine antibody
      specificities. According to these results we can suggest that LB should be used
      as the method of choice to search for paraneoplastic antibodies.

PMID- 20136625
TI  - Nanoemulsions as vehicles for topical administration of glycyrrhetic acid:
      characterization and in vitro and in vivo evaluation.
AB  - Nano-emulsions are innovative colloidal systems characterized by high kinetic
      stability, low viscosity, and optical transparency, which make them very
      attractive in many dermatological applications. Furthermore their small size
      seems to favor the topical administration of actives which scarcely cross the
      skin. In the light of these interesting features, the present study was aimed to
      the evaluation, in vitro and in vivo, of glycyrrhetic acid (GA) release through
      the skin from the nanoemulsion system. GA-loaded nanoemulsion (GA(N)) was
      prepared by phase inversion temperature (PIT) method, and was characterized in
      order to determine mean droplet size and its stability during a well-defined
      storage period. Further Cryo-TEM studies were performed to obtain information
      regarding nanoemulsion structure. The GA release pattern from nanoemulsion was
      evaluated in vitro, to determine its percutaneous absorption through excised
      human skin (stratum corneum and epidermis, SCE), and in vivo evaluating GA
      topical anti-inflammatory activity on healthy human volunteers by the UVB-induced
      erythema model. Nanoemulsions prepared by PIT method showed a mean droplet
      diameter of 210 nm that drastically changed during a storage of 5 weeks at room
      temperature. In vitro and in vivo evidence showed that the nanoemulsion system
      significantly increased the transdermal permeability of GA in comparison to a
      control O/W emulsion (GA(O/W)) containing the same amount of active compound.

PMID- 20136626
TI  - Nuclear factor-kappaB signaling: a contributor in leukemogenesis and a target for
      pharmacological intervention in human acute myelogenous leukemia.
AB  - Acute myeloid leukemia (AML) is an aggressive malignancy with only 40%-50% long
      term survival even for younger patients who can receive the most aggressive
      therapy. For elderly patients who only receive palliative treatment, the median
      survival is only 2-3 months. Inhibition of the nuclear factor-kappaB (NF-kappaB)
      transcription factor family is one of the therapeutic strategies that are
      considered in AML. NF-kappaB is an important regulator of several biological
      processes that are involved in leukemogenesis, including proliferation,
      differentiation, autophagy, and apoptosis. Constitutive NF-kappaB activation has
      been detected in AML cells and NF-kappaB inhibition is therefore a possible
      therapeutic strategy in AML. Multiple pharmacological agents have shown
      inhibitory effects against NF-kappaB signaling pathways, including proteasome
      inhibitors as well as the more-specific agents that are directed against various
      steps of this signaling pathway. Recent studies strongly suggest that primary
      human AML cells (including AML stem cells) are susceptible to NF-kappaB
      inhibition, but this therapeutic approach should possibly be combined with other
      therapeutic agents to achieve a combined effect both on NF-kappaB transcriptional
      activity, tumor suppressor-induced signaling, and stress-induced pathways. The
      clinical documentation with regard to the efficiency and safety of NF-kappaB
      inhibition is still limited, but experimental evidence strongly suggests that NF
      kappaB inhibition should be further investigated in human AML.

PMID- 20136627
TI  - Inflammation versus adaptive immunity in cancer pathogenesis.
AB  - Cancer pathogenesis is initiated and modulated in an interplay between the
      malignant transformed cells, the surrounding stroma, and the innate and adaptive
      immune system. These interactions are complex, and components of the immune
      system act as both defense mechanisms against and contributors to tumor
      initiation, tumor growth, invasivity, and development of metastases. Inflammatory
      conditions help to establish a microenvironment promoting cancer development,
      whereas a malignant tumor feeds the inflammatory response and accelerates tumor
      growth. However, mouse models and epidemiological and clinical data demonstrate
      that an intact immune system is associated with a favorable prognosis, although
      the inflammatory response and the adaptive immune system share many cellular and
      humoral features. Here, we review the emerging concepts in cancer pathogenesis
      where the inflammatory and adaptive components of the immune system play an
      important role in the interaction with the tumor and stromal tissue.

PMID- 20136628
TI  - Gain of antitumor functions and induction of differentiation in cancer stem cells
      contribute to complete cure and no relapse.
AB  - The progeny of the mutated cell is maintained in a self-renewing tissue stem cell
      and its immediate progeny or due to cellular components that display stem cell
      like properties known as cancer stem cells (CSCs) that grow into cancer. Failure
      to achieve complete and safe eradication of cancer is due to the presence of
      quiescent population of cancer stem cells. Understanding and interfering with the
      processes of transformation of normal stem cells into their malignant
      counterparts, their micro-environmental niche and the mechanisms responsible for
      therapeutic resistance in CSCs enhance the curative efficacy of clinical
      elimination of all tumor cells. Functional identification of the molecular
      targets of CSCs provides useful insights for characterization of their response
      to particular therapy protocols. This review also focuses on the potential
      implications of promising novel therapies in suppression of oncogenic pathways
      specific to CSCs including their self-renewal capacity, property of drug
      transportation, seeding and oxidative stress, activation of apoptosis through the
      gain of antitumor molecules, restoration of DNA repair mechanisms and
      differentiation therapy that allows the terminal differentiation of CSCs thereby
      depleting their pool, all contribute to long-term disease control and improved
      patient survival. Significant developments in the optimization of combinational
      CSC-targeted therapies would lead to the improved outcome with great difference
      thus substantiating its profound impact in disease free survival with no relapse.

PMID- 20136629
TI  - Structural and expression changes of septins in myeloid neoplasia.
AB  - Septins are an evolutionarily conserved family of GTP-binding proteins that
      associate with cellular membranes and the actin and microtubule cytoskeletons.
      Fourteen septin genes have been characterized to date (SEPT1 to SEPT14) in
      humans. Septins have been reported to be misregulated in various human diseases,
      including neurological disorders, infection, and neoplasia. In this review, we
      describe what is known thus far about septin deregulation in myeloid neoplasia.
      Septin abnormalities in myeloid neoplasia can be divided into two major groups.
      First, some septins (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) have been repeatedly
      identified as in-frame fusion partners of the MLL gene in de novo and therapy
      related myeloid neoplasia, in both children and adults. Second, deregulation of
      the expression of septin family genes in hematological cancers can be observed
      either with or without the concomitant presence of MLL gene fusions. Although
      current hypotheses regarding the roles of septins in oncogenesis remain
      speculative for the most part, the fundamental roles of septins in cytokinesis,
      membrane remodeling, and compartmentalization can provide some clues on how
      abnormalities in the septin cytoskeleton could be involved in neo-plastic
      disorders.

PMID- 20136631
TI  - Self-emulsifying drug delivery systems (SEDDS): formulation development,
      characterization, and applications.
AB  - Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in
      improving oral bioavailability of poorly water-soluble drugs. Following their
      oral administration, these systems rapidly disperse in gastrointestinal fluids,
      yielding micro- or nanoemulsions containing the solubilized drug. Owing to its
      miniscule globule size, the micro/nanoemulsifed drug can easily be absorbed
      through lymphatic pathways, bypassing the hepatic first-pass effect. We present
      an exhaustive and updated account of numerous literature reports and patents on
      diverse types of self-emulsifying drug formulations, with emphasis on their
      formulation, characterization, and systematic optimization strategies. Recent
      advancements in various methodologies employed to characterize their globule size
      and shape, ability to encapsulate the drug, gastrointestinal and thermodynamic
      stability, rheological characteristics, and so forth, are discussed
      comprehensively to guide the formula-tor in preparing an effective and robust
      SEDDS formulation. Also, this exhaustive review offers an explicit discussion on
      vital applications of the SEDDS in bioavailability enhancement of various drugs,
      outlining an overview on myriad in vitro, in situ, and ex vivo techniques to
      assess the absorption and/ or permeation potential of drugs incorporated in the
      SEDDS in animal and cell line models, and the subsequent absorption pathways
      followed by them. In short, the current article furnishes an updated compilation
      of wide-ranging information on all the requisite vistas of the self-emulsifying
      formulations, thus paving the way for accelerated progress into the SEDDS
      application in pharmaceutical research.

PMID- 20136632
TI  - Insertion of an NPVY sequence into the cytosolic domain of the erythropoietin
      receptor selectively affects erythropoietin-mediated signalling and function.
AB  - EPO (erythropoietin), the major hormone regulating erythropoiesis, functions via
      activation of its cell-surface receptor (EPO-R) present on erythroid progenitor
      cells. One of the most striking properties of EPO-R is its low expression on the
      cell surface, as opposed to its high intracellular levels. The low cell-surface
      expression of EPO-R may thus limit the efficacy of EPO that is routinely used to
      treat primary and secondary anaemia. In a recent study [Nahari, Barzilay,
      Hirschberg and Neumann (2008) Biochem. J. 410, 409-416] we have shown that
      insertion of an NPVY sequence into the intracellular domain of EPO-R increases
      its cell-surface expression. In the present study we demonstrate that this NPVY
      EPO-R insert has a selective effect on EPO-mediated downstream signalling in
      Ba/F3 cells expressing this receptor (NPVY-EPO-R). This is monitored by increased
      phosphorylation of the NPVY-EPO-R (on Tyr479), Akt, JAK2 (Janus kinase 2) and
      ERK1/2 (extracellular-signal-regulated kinase 1/2), but not STAT5 (signal
      transducer and activator of transcription 5), as compared with cells expressing
      wild-type EPO-R. This enhanced signalling is reflected in augmented proliferation
      at low EPO levels (0.05 units/ml) and protection against etoposide-induced
      apoptosis. Increased cell-surface levels of NPVY-EPO-R are most probably not
      sufficient to mediate these effects as the A234E-EPO-R mutant that is expressed
      at high cell-surface levels does not confer an augmented response to EPO. Taken
      together, we demonstrate that insertion of an NPVY sequence into the cytosolic
      domain of the EPO-R confers not only improved maturation, but also selectively
      affects EPO-mediated signalling resulting in an improved responsiveness to EPO
      reflected in cell proliferation and protection against apoptosis.

PMID- 20136633
TI  - Novel insights into mannitol metabolism in the fungal plant pathogen Botrytis
      cinerea.
AB  - In order to redefine the mannitol pathway in the necrotrophic plant pathogen
      Botrytis cinerea, we used a targeted deletion strategy of genes encoding two
      proteins of mannitol metabolism, BcMTDH (B. cinerea mannitol dehydrogenase) and
      BcMPD (B. cinerea mannitol-1-phosphate dehydrogenase). Mobilization of mannitol
      and quantification of Bcmpd and Bcmtdh gene transcripts during development and
      osmotic stress confirmed a role for mannitol as a temporary and disposable carbon
      storage compound. In order to study metabolic fluxes, we followed conversion of
      labelled hexoses in wild-type and DeltaBcmpd and DeltaBcmtdh mutant strains by in
      vivo NMR spectroscopy. Our results revealed that glucose and fructose were
      metabolized via the BcMPD and BcMTDH pathways respectively. The existence of a
      novel mannitol phosphorylation pathway was also suggested by the NMR
      investigations. This last finding definitively challenged the existence of the
      originally postulated mannitol cycle in favour of two simultaneously expressed
      pathways. Finally, physiological and biochemical studies conducted on double
      deletion mutants (DeltaBcmpdDeltaBcmtdh) showed that mannitol was still produced
      despite a complete alteration of both mannitol biosynthesis pathways. This
      strongly suggests that one or several additional undescribed pathways could
      participate in mannitol metabolism in B. cinerea.

PMID- 20136634
TI  - Increased plasma concentrations of anterior gradient 2 protein are positively
      associated with ovarian cancer.
AB  - Ovarian cancer is often asymptomatic and is diagnosed at an advanced stage with
      poor survival rates, thus there is an urgent need to develop biomarkers for
      earlier detection of ovarian cancer. In the present study, we demonstrate for the
      first time that the previously reported metastasis-inducing protein AGR2
      (anterior gradient protein 2) can be detected in the blood of ovarian cancer
      patients. Using a newly developed ELISA, we show significantly increased
      concentrations of AGR2 protein in plasma from cancer patients relative to normal
      controls. Plasma AGR2 concentrations were highest in stages II and III ovarian
      cancer patients and were similarly elevated in patients with both serous and non
      serous tumours. The identification of elevated plasma concentrations of AGR2 may
      provide a useful biomarker to aid in the discrimination of normal and ovarian
      cancer patients particularly when used in combination with CA125.

PMID- 20136635
TI  - Formation of transient dimers by a retroviral protease.
AB  - Retroviral proteases have been shown previously to be only active as homodimers.
      They are essential to form the separate and active proteins from the viral
      precursors. Spumaretroviruses produce separate precursors for Gag and Pol, rather
      than a Gag and a Gag-Pol precursor. Nevertheless, processing of Pol into a PR
      (protease)-RT (reverse transcriptase) and integrase is essential in order to
      obtain infectious viral particles. We showed recently that the PR-RT from a
      simian foamy virus, as well as the separate PRshort (protease) domain, exhibit
      proteolytic activities, although only monomeric forms could be detected. In the
      present study, we demonstrate that PRshort and PR-RT can be inhibited by the
      putative dimerization inhibitor cholic acid. Various other inhibitors, including
      darunavir and tipranavir, known to prevent HIV-1 PR dimerization in cells, had no
      effect on foamy virus protease in vitro. 1H-15N HSQC (heteronuclear single
      quantum coherence) NMR analysis of PRshort indicates that cholic acid binds in
      the proposed PRshort dimerization interface and appears to impair formation of
      the correct dimer. NMR analysis by paramagnetic relaxation enhancement resulted
      in elevated transverse relaxation rates of those amino acids predicted to
      participate in dimer formation. Our results suggest transient PRshort homodimers
      are formed under native conditions but are only present as a minor transient
      species, which is not detectable by traditional methods.

PMID- 20136636
TI  - Functional characterization of polypeptide release factor 1b in the ciliate
      Euplotes.
AB  - In higher eukaryotes, RF-I (class I release factor) [eRF1 (eukaryotic release
      factor 1)] is responsible for stop codon recognition and promotes nascent
      polypeptide release from the ribosome. Interestingly, two class I RFs, eRF1a and
      eRF1b, have been identified among the ciliates Euplotes, which are variant code
      organisms. In the present study, we analysed the comparative expression of eRF1a
      and eRF1b in Euplotes cells, demonstrating that the expression of eRF1b was
      higher than that of eRF1a. An interaction between eRF1b and eRF3 was confirmed,
      suggesting that an eRF1b function is facilitated by eRF3. Co-localization of both
      eRF1s indicated that they function in the same subcellular location in Euplotes
      cells. We also analysed the characteristics of stop codon discrimination by
      eRF1b. Like eRF1a, eRF1b recognized UAA and UAG as stop codons, but not UGA. This
      finding disagreed with the deduced characteristics of eRF1a/eRF1b from the
      classic hypothesis of 'anticodon-mimicry' proposed by Muramatsu et al.
      [Muramatsu, Heckmann, Kitanaka and Kuchino (2001) FEBS Lett. 488, 105-109].
      Mutagenesis experiments indicated that the absolutely conserved amino acid motif
      'G31T32' (numbered as for human eRF1) in eRF1b was the key to efficient stop
      codon recognition by eRF1b. In conclusion, these findings support and improve the
      'cavity model' of stop codon discrimination by eRF1 proposed by Bertram et al.
      [Bertram, Bell, Ritchie, Fullerton and Stansfield (2000) RNA 6, 1236-1247] and
      Inagaki et al. [Inagaki, Blouin, Doolittle and Roger (2002) Nucleic Acids Res.
      30, 532-544].

PMID- 20136637
TI  - Phosphorylation states of STAT3 and ERKs in mouse embryonic stem cells.
AB  - Mouse ES (embryonic stem) cells are maintained in an undifferentiated state in
      the presence of LIF (leukaemia-inhibitory factor). In general, LIF engages a
      heterodimeric receptor complex composed of a low-affinity LIF receptor (LIFRbeta)
      and gp130, and activates STAT3 (signal transducers and activators of
      transcription 3) and ERKs (extracellular signal-regulated kinases). However, in
      undifferentiated ES cells in the presence of LIF, STAT3 is phosphorylated but
      ERKs are not. The removal of LIF-induced dephosphorylation of phospho-STAT3 and
      phosphorylation of ERKs resulted in the differentiation of ES cells. Here, we
      show that the dephosphorylation of phospho-STAT3 corresponds to the activation of
      ERKs pathway from the time-courses of the phosphorylation levels in detail. We
      found that the treatment of membrane-permeable STAT3IP (STAT3 inhibitory
      peptide), which inhibits homodimeric formation of STAT3, induced the
      phosphorylation of ERKs in ES cells in the presence of LIF. In addition, the
      removal of LIF decreased the expression level of SOCS3 (suppressor of cytokine
      signalling 3), a negative regulator of LIF signalling, and the phosphorylation of
      ERKs was efficiently induced in the ES cells where SOCS3 was down-regulated.
      These results suggested that LIF-induced SOCS3 suppressed the ERKs activation
      pathway in undifferentiated ES cells, and the down-regulation of SOCS3 by the
      removal of LIF triggered the phosphorylation of ERKs.

PMID- 20136638
TI  - Correlation of IMPDH1 gene polymorphisms with subclinical acute rejection and
      mycophenolic acid exposure parameters on day 28 after renal transplantation.
AB  - The risk of acute rejection in patients with higher exposure to mycophenolic acid
      (MPA), the active metabolite of mycophenolate mofetil (MMF), might be due to
      inosine 5'-monophosphate dehydrogenase (IMPDH) polymorphisms. The correlations
      with subclinical acute rejection, IMPDH1 polymorphisms and MPA exposure on day 28
      post-transplantation were investigated in 82 Japanese recipients. Renal
      transplant recipients were given combination immunosuppressive therapy consisting
      of tacrolimus and 1.0, 1.5 or 2.0 g/day of MMF in equally divided doses every 12
      hr at designated times. There were no significant differences in the incidence of
      subclinical acute rejection between IMPDH1 rs2278293 or rs2278294 polymorphisms
      (p = 0.243 and 0.735, respectively). However, in the high MPA night-time exposure
      range (AUC > 60 microg x h/ml and C(0 )> or = 1.9 microg/ml), there was a
      significant difference in the incidence of subclinical acute rejection between
      IMPDH1 rs2278293 A/A, A/G and G/G genotypes (each p = 0.019), but not the IMPDH1
      rs2278294 genotype. In the higher daytime MPA exposure range, patients with the
      IMPDH1 rs2278293 G/G genotype also tended to develop subclinical acute rejection.
      In patients with the IMPDH rs2278293 A/A genotype, the risk of subclinical acute
      rejection episode tends to be low and the administration of MMF was effective.
      The risk of subclinical acute rejection for recipients who cannot adapt in
      therapeutic drug monitoring (TDM) of MPA seems to be influenced by IMPDH1
      rs2278293 polymorphism. The prospective analysis of IMPDH1 rs2278293 polymorphism
      as well as monitoring of MPA plasma concentration after transplantation might
      help to improve MMF therapy.

PMID- 20136639
TI  - Comprehensive standardized data definitions for acute coronary syndrome research
      in emergency departments in Australasia.
AB  - Patients with chest discomfort or other symptoms suggestive of acute coronary
      syndrome are one of the most common categories seen in many Emergency Departments
      (EDs). Although the recognition of patients at high risk of acute coronary
      syndrome has improved steadily, identifying the majority of chest pain
      presentations who fall into the low-risk group remains a challenge. Research in
      this area needs to be transparent, robust, applicable to all hospitals from large
      tertiary centres to rural and remote sites, and to allow direct comparison
      between different studies with minimum patient spectrum bias. A standardized
      approach to the research framework using a common language for data definitions
      must be adopted to achieve this. The aim was to create a common framework for a
      standardized data definitions set that would allow maximum value when
      extrapolating research findings both within Australasian ED practice, and across
      similar populations worldwide. Therefore a comprehensive data definitions set for
      the investigation of non-traumatic chest pain patients with possible acute
      coronary syndrome was developed, specifically for use in the ED setting. This
      standardized data definitions set will facilitate 'knowledge translation' by
      allowing extrapolation of useful findings into the real-life practice of
      emergency medicine.

PMID- 20136640
TI  - Accuracy of bedside ultrasound for the detection of soft tissue foreign bodies by
      emergency doctors.
AB  - OBJECTIVE: To assess the ability of emergency physicians and emergency trainees
      to detect soft tissue foreign bodies using typical ultrasound equipment. METHODS:
      Following a 20 min interactive training session, emergency physicians and
      emergency trainees were assessed on ability to identify subcutaneous foreign
      bodies (wood, glass, plastic, gravel and metal) embedded in an experimental model
      containing both sham and real entry point incisions. In the second phase of the
      experiment accuracy of detection of multiple foreign bodies was assessed in a
      similar sonographic phantom. RESULTS: Six emergency physicians and 14 emergency
      trainees performed a total of 400 individual sonographic examinations. Emergency
      physicians correctly identified 29 of 30 foreign bodies and returned sensitivity,
      specificity, positive predictive value and negative predictive value of 96.7%,
      70%, 76.3% and 95.5%, respectively. Trainees correctly identified 60 of 70
      foreign bodies and returned sensitivity, specificity, positive predictive value
      and negative predictive value of 85.7%, 82.9%, 83.3% and 85.3%. Correct
      identification of the number of foreign bodies present, when multiple, was low
      (25% physician vs 36% trainee). CONCLUSION: These data suggest ultrasound in the
      hands of emergency doctors might be useful as an initial screening tool for
      detection of soft tissue foreign bodies.

PMID- 20136641
TI  - Verbal dyspnoea score predicts emergency department departure status in patients
      with shortness of breath.
AB  - OBJECTIVES: We examined whether a previously validated verbal dyspnoea rating
      scale, and/or other demographic and clinical parameters, could predict ED
      departure status, among ED patients presenting with shortness of breath. METHODS:
      In this prospective observational study, a convenience sample of patients
      presenting to an inner urban adult tertiary hospital ED with shortness of breath
      were assessed at triage using objective and subjective breathlessness parameters.
      These included respiratory rate, oxygen saturation, heart rate, systolic blood
      pressure and verbal dyspnoea scores. A verbal dyspnoea score for worst dyspnoea
      during the current episode and basic demographic and presentation characteristics
      were also collected. These variables were assessed as predictors of ED departure
      status (inpatient admission or ED discharge) using logistic regression. RESULTS:
      From a sample of 253 participants, verbal dyspnoea scores > or =8 predicted
      inpatient admission 89% specificity (95% confidence interval [CI] 82.1-93.4), and
      scores < or =3 predicted discharge with 95% specificity (95% CI 89.5-98.0). For
      patients with shortness of breath as the primary complaint, the combination of
      verbal dyspnoea score > or =6, heart rate > or =94 bpm at triage and ambulance
      arrival predicted admission with 90% sensitivity (95% CI 82-95%) and 84%
      specificity (95% CI 73-92%). These same variables predicted admission for all
      patients with 84% sensitivity (95% CI 75.8-89.2) and 79% specificity (95% CI 71.5
      85.5). CONCLUSION: Verbal dyspnoea score, alone and in combination with heart
      rate and arrival transport, can accurately predict admission. Once validated they
      might be useful in assessing, prioritizing and making rapid site of care
      decisions for breathless patients presenting to the ED.

PMID- 20136642
TI  - Short-term quality of life following partial breast irradiation with balloon
      brachytherapy- comparison with whole breast irradiation.

PMID- 20136643
TI  - Solitary nasal cavity metastasis of breast cancer.

PMID- 20136644
TI  - Predicting non-sentinel lymph node status in breast cancer patients with sentinel
      lymph node involvement: evaluation of two scoring systems.
AB  - The aim of this study was to validate a nomogram and a scoring system to predict
      non-sentinel lymph node status in breast cancer patients with sentinel lymph node
      (SLN) involvement. A total of 516 breast cancer patients underwent sentinel lymph
      node biopsy at our institution from January 2001 to August 2006. A prospective
      database was used to identify breast cancer patients with a positive SLN biopsy
      examination who underwent a completion axillary lymph node dissection. A total of
      114 patients were identified. The Memorial Sloan-Kettering Cancer Center (MSKCC)
      nomogram and an axilla scoring system from Paris (Hopital Tenon) were used to
      predict the probability of having non-SLN involvement. One hundred fourteen
      patients were included in the study. The areas under the receiver operating
      characteristics (ROC) curves were 0.671 (95% CI: 0.552-0.790) for the MSKCC
      nomogram and 0.703 (95% CI: 0.596-0.811) for the Tenon score. The univariate
      analysis shows that size of SLN metastases, the number of positive and negative
      SLN and the proportion of positive SLN were statistically significant. On
      multivariate logistic regression analysis, the size of SLN metastases and the
      proportion of positive SLN were statistically significant. The two scoring
      systems are similar according to their area under ROC curves, but should be
      improved to be valid and determinant to the general population. Meanwhile, the
      use of scoring systems could be applied in an individual manner in some patients.

PMID- 20136645
TI  - In newly diagnosed breast cancer, screening MRI of the contralateral breast
      detects mammographically occult cancer, even in elderly women: the mayo clinic in
      Florida experience.
AB  - The role of magnetic resonance imaging (MRI) in patients with newly diagnosed
      breast cancer is somewhat controversial. The purpose of this study was to
      evaluate the prevalence of synchronous, occult contralateral breast cancer
      detected by MRI but not by mammography or clinical breast examination in women
      with newly diagnosed breast cancer, including those aged 70 years or older at our
      institution. MRI results for women with newly diagnosed breast cancer who
      underwent bilateral breast MRI after negative mammography and clinical
      examination between February 2003 and November 2007 at Mayo Clinic in Florida
      were reviewed. The prevalence of pathologically confirmed contralateral carcinoma
      diagnosed solely by MRI was determined and analyzed in the context of age, family
      history, menopausal status, breast density, and primary-tumor characteristics.
      Logistic regression was used to explore the association between contralateral
      carcinoma and potential patient risk factors. A total of 425 women were
      evaluated, of whom 129 (30%) were aged 70 years or older. A contralateral biopsy
      was recommended and performed solely on the basis of MRI in 72 of the 425 women
      (17%). Sixteen of these 72 women (22%) had pathologically confirmed carcinoma,
      including seven in the older subgroup. The prevalence of clinically and
      mammographically occult contralateral carcinoma detected by MRI was 3.8% (16/425)
      overall and 5.4% (7/129) in the group of older women. When potential risk factors
      for contralateral breast cancer were evaluated, postmenopausal status was the
      only significant predictor of contralateral cancer detected by MRI (p = 0.016).
      We concluded that contralateral breast screening with MRI should be considered in
      postmenopausal women with newly diagnosed breast cancer, even those aged 70 years
      or older at diagnosis.

PMID- 20136646
TI  - Breast cancer in Nigeria: is non-adherence to chemotherapy schedules a major
      factor in the reported poor treatment outcome?

PMID- 20136648
TI  - Better than expected survival after primary intracerebral hemorrhage in patients
      with untreated hypertension despite high admission blood pressures.
AB  - BACKGROUND: Hypertension is the most important modifiable risk factor for primary
      intracerebral hemorrhage (ICH), but little is known of the effect of preceding
      hypertension on outcome. Because high mean arterial blood pressure (MABP) at
      admission is an independent predictor of early death in patients with ICH, we
      explored its role on survival and poor outcome separately in normotensive
      subjects and subjects with treated and untreated hypertension. METHODS: We
      assessed clinical data and the 3-month outcome of patients with spontaneous ICH
      (n = 453) admitted to the stroke unit of Oulu University Hospital between 1993
      and 2004. Standard medical treatment was used to lower MABP from levels >127 mmHg
      to <120 mmHg. RESULTS: Overall mortality within 3 months was 28%. Patients with
      untreated hypertension had significantly lower mortality (6%) than those with
      treated hypertension (36%, P < 0.001) or those without hypertension (25%, P <
      0.01). High admission MABP associated with early death in normotensive subjects
      (P < 0.05) and those on medication for hypertension (P < 0.01) but not in those
      with untreated hypertension. Patients with untreated hypertension were younger
      and had less frequently cardiac disease, diabetes, and/or warfarin or aspirin
      medications, but they showed the highest blood pressures (BPs) at admission.
      Amongst patients with high admission MABP, favorable outcome was seen most
      frequently in those who had untreated hypertension. Hematoma growth did not
      associate with high MABP amongst them. CONCLUSION: Despite their higher BP values
      at admission, subjects with untreated hypertension showed better survival and
      more frequently favorable outcome after BP-lowering therapy than other patients.

PMID- 20136647
TI  - EFNS guidelines on the use of neuroimaging in the management of motor neuron
      diseases.
AB  - BACKGROUND AND PURPOSE: These European Federation of Neurological Societies
      guidelines on neuroimaging of motor neuron diseases (MNDs) are designed to
      provide practical help for the neurologists to make appropriate use of
      neuroimaging techniques in patients with MNDs, which ranges from diagnostic and
      monitoring aspects to the in vivo study of the pathobiology of such conditions.
      METHODS: Literature searches were performed before expert members of the Task
      Force wrote proposal. Then, consensus was reached by circulating drafts of the
      manuscript to the Task Force members and by discussion of the classification of
      evidence and recommendations. RESULTS AND CONCLUSIONS: The use of conventional
      MRI in patients suspected of having a MND is yet restricted to exclude other
      causes of signs and symptoms of MN pathology [class IV, level good clinical
      practice point (GCPP)]. Although the detection of corticospinal tract
      hyperintensities on conventional MRI and a T2-hypointense rim in the pre-central
      gyrus can support a pre-existing suspicion of MND, the specific search of these
      abnormalities for the purpose of making a firm diagnosis of MND is not
      recommended (class IV, level GCPP). At present, advanced neuroimaging techniques,
      including diffusion tensor imaging and proton magnetic resonance spectroscopic
      imaging, do not have a role in the diagnosis or routine monitoring of MNDs yet
      (class IV, level GCPP). However, it is strongly advisable to incorporate measures
      derived from these techniques into new clinical trials as exploratory outcomes to
      gain additional insights into disease pathophysiology and into the value of these
      techniques in the (longitudinal) assessment of MNDs (class IV, level GCPP).

PMID- 20136649
TI  - Intravenous thrombolysis in patients with stroke attributable to small artery
      occlusion.
AB  - BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial
      independent of the underlying etiology. Recent observations raised concern that
      IVT might cause harm in patients with strokes attributable to small artery
      occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in
      this study. METHODS: We used the Swiss IVT databank to compare outcome and
      complications of IVT-treated SAO-patients with IVT-treated patients with other
      etiologies (non-SAO-patients). Main outcome and complication measures were
      independence (modified Rankin scale <or=2) at 3 months, intracranial hemorrhage
      (ICH), and recurrent ischaemic stroke. RESULTS: Sixty-five (6.2%) of 1048 IVT
      treated patients had SAO. Amongst SAO-patients, 1.5% (1/65) patients died,
      compared to 11.2% (110/983) in the non-SAO-group (P = 0.014). SAO-patients
      reached independence more often than non-SAO-patients (75.4% versus 58.9%; OR
      2.14 (95% CI 1.20-3.81; P = 0.001). This association became insignificant after
      adjustment for age, gender, and stroke severity (OR 1.41 95% CI 0.713-2.788; P =
      0.32). Glucose level and (to some degree) stroke severity but not age predicted 3
      month-independence in IVT-treated SAO-patients. ICHs (all/symptomatic) were
      similar in SAO- (12.3%/4.6%) and non-SAO-patients (13.4%/5.3%; P > 0.8). Fatal
      ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients.
      Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and
      in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died
      less often and reached independence more often than IVT-treated non-SAO-patients.
      However, the variable 'SAO' was a dependent rather than an independent outcome
      predictor. The absence of an excess in ICH indicates that IVT seems not to be
      harmful in SAO-patients.

PMID- 20136650
TI  - Random forest can predict 30-day mortality of spontaneous intracerebral
      hemorrhage with remarkable discrimination.
AB  - BACKGROUND AND PURPOSE: Risk-stratification models based on patient and disease
      characteristics are useful for aiding clinical decisions and for comparing the
      quality of care between different physicians or hospitals. In addition,
      prediction of mortality is beneficial for optimizing resource utilization. We
      evaluated the accuracy and discriminating power of the random forest (RF) to
      predict 30-day mortality of spontaneous intracerebral hemorrhage (SICH). METHODS:
      We retrospectively studied 423 patients admitted to the Taichung Veterans General
      Hospital who were diagnosed with spontaneous SICH within 24 h of stroke onset.
      The initial evaluation data of the patients were used to train the RF model.
      Areas under the receiver operating characteristic curves (AUC) were used to
      quantify the predictive performance. The performance of the RF model was compared
      to that of an artificial neural network (ANN), support vector machine (SVM),
      logistic regression model, and the ICH score. RESULTS: The RF had an overall
      accuracy of 78.5% for predicting the mortality of patients with SICH. The
      sensitivity was 79.0%, and the specificity was 78.4%. The AUCs were as follows:
      RF, 0.87 (0.84-0.90); ANN, 0.81 (0.77-0.85); SVM, 0.79 (0.75-0.83); logistic
      regression, 0.78 (0.74-0.82); and ICH score, 0.72 (0.68-0.76). The discriminatory
      power of RF was superior to that of the other prediction models. CONCLUSIONS: The
      RF provided the best predictive performance amongst all of the tested models. We
      believe that the RF is a suitable tool for clinicians to use in predicting the 30
      day mortality of patients after SICH.

PMID- 20136651
TI  - Hepatic stimulator substance mitigates hepatic cell injury through suppression of
      the mitochondrial permeability transition.
AB  - Hepatic stimulator substance (HSS) has been shown to protect liver cells from
      various toxins. However, the mechanism by which HSS protects hepatocytes remains
      unclear. In this study, we established BEL-7402 cells that stably express HSS and
      analyzed the protective ability of HSS on cells through mitochondrial
      permeability (MP). After administration of carbonyl cyanide m
      chlorophenylhydrazone (CCCP), a specific agent that leads to depolarization of
      the mitochondrial transmembrane potential, the apoptosis rate of HSS-expressing
      cells was significantly reduced, as measured using Hoechst staining and flow
      cytometry. The mitochondrial membrane transition and cytochrome c leakage were
      significantly inhibited in the HSS-expressing cells as compared with the
      untransfected cells, and, as a consequence, the cellular ATP content in the HSS
      expressing cells was relatively preserved. Additionally, decreased caspase-3
      activity was observed in the HSS-expressing cells treated with CCCP as compared
      with the vector-transfected cells and cells expressing mutant HSS. Furthermore,
      silencing of HSS expression using small interfering RNA accelerated CCCP-induced
      apoptosis. In isolated mitochondria, recombinant HSS reduced the release of
      cytochrome c induced by CCCP, indicating a possible role for HSS in regulation of
      mitochondrial permeability transition (MPT). HSS-expressing BEL-7402 cells are
      resistant to CCCP injury, and HSS protection is identical to that observed with
      cyclosporin A, an inhibitor of MPT. Therefore, we propose that the protective
      effect of HSS may be associated with blockade of MPT.

PMID- 20136652
TI  - Developmental consequences of alternative Bcl-x splicing during preimplantation
      embryo development.
AB  - Elevated cell death in human preimplantation embryos is one of the cellular
      events compromising pregnancy rates after assisted reproductive technology
      treatments. We therefore explored the molecular pathways regulating cell death at
      the blastocyst stage in human embryos cultured in vitro. Owing to limited
      availability of human embryos, these pathways were further characterized in mouse
      blastocysts. Gene expression studies revealed a positive correlation between the
      cell death index and the expression of Bcl-x transcript. Cell death activation in
      human blastocysts was accompanied by changes in Bcl-x splicing, favoring
      production of Bcl-xS, an activator of cell death. Expression of Bcl-xS was
      detected in a subset of human blastocysts that show particular clustering in
      dying and/or dead cells. Altering the Bcl-xL/Bcl-xS ratio in mouse embryos, in
      antisense experiments, confirmed that upregulation of Bcl-xS, with concomitant
      downregulation of Bcl-xL, compromised developmental potential and committed a
      subset of cells to undergoing cell death. This was accompanied by increased
      accumulation of reactive oxygen species levels without any impact on mtDNA
      content. In addition, altered Bcl-x splicing in favor of Bcl-xS was stimulated by
      culture in HTF medium or by addition of excessive glucose, leading to compromised
      embryo development. Thus, we conclude that inappropriate culture conditions
      affect Bcl-x isoform expression, contributing to compromised preimplantation
      embryo development.

PMID- 20136653
TI  - Animal models of amyloid-beta-related pathologies in Alzheimer's disease.
AB  - In the early 1990s, breakthrough discoveries on the genetics of Alzheimer's
      disease led to the identification of missense mutations in the amyloid-beta
      precursor protein gene. Research findings quickly followed, giving insights into
      molecular pathogenesis and possibilities for the development of new types of
      animal models. The complete toolbox of transgenic techniques, including
      pronuclear oocyte injection and homologous recombination, has been applied in the
      Alzheimer's disease field, to produce overexpressors, knockouts, knockins and
      regulatable transgenics. Transgenic models have dramatically advanced our
      understanding of pathogenic mechanisms and allowed therapeutic approaches to be
      tested. Following a brief introduction to Alzheimer's disease, various
      nontransgenic and transgenic animal models are described in terms of their values
      and limitations with respect to pathogenic, therapeutic and functional
      understandings of the human disease.

PMID- 20136654
TI  - Upregulation of the alpha-secretase ADAM10--risk or reason for hope?
AB  - A decade ago, a disintegrin and metalloproteinase 10 (ADAM10) was identified as
      an alpha-secretase and as a key proteinase in the processing of the amyloid
      precursor protein. Accordingly, the important role that it plays in Alzheimer's
      disease was manifested. Animal models with an overexpression of ADAM10 revealed a
      beneficial profile of the metalloproteinase with respect to learning and memory,
      plaque load and synaptogenesis. Therefore, ADAM10 presents a worthwhile target
      with respect to the treatment of a neurodegenerative disease such as Morbus
      Alzheimer. Initially, ADAM10 was suggested to be an enzyme, shaping the
      extracellular matrix by cleavage of collagen type IV, or to be a tumour necrosis
      factor alpha convertase. In a relatively short time, a wide variety of additional
      substrates (with amyloid precursor protein probably being the most prominent) has
      been identified and the search is still ongoing. Hence, any side effects
      concerning the therapeutic enhancement of ADAM10 alpha-secretase activity have to
      be considered. The present review summarizes our knowledge about the structure
      and function of ADAM10 and highlights the opportunities for enhancing the
      expression and/or activity of the alpha-secretase as a therapeutic target.

PMID- 20136655
TI  - Pronounced adipogenesis and increased insulin sensitivity caused by
      overproduction of prostaglandin D2 in vivo.
AB  - Lipocalin-type prostaglandin (PG) D synthase is expressed in adipose tissues and
      involved in the regulation of glucose tolerance and atherosclerosis in type 2
      diabetes. However, the physiological roles of PGD(2) in adipogenesis in vivo are
      not clear, as lipocalin-type prostaglandin D synthase can also act as a
      transporter for lipophilic molecules, such as retinoids. We generated transgenic
      (TG) mice overexpressing human hematopoietic PGDS (H-PGDS) and investigated the
      in vivo functions of PGD(2) in adipogenesis. PGD(2) production in white adipose
      tissue of H-PGDS TG mice was increased approximately seven-fold as compared with
      that in wild-type (WT) mice. With a high-fat diet, H-PGDS TG mice gained more
      body weight than WT mice. Serum leptin and insulin levels were increased in H
      PGDS TG mice, and the triglyceride level was decreased by about 50% as compared
      with WT mice. Furthermore, in the white adipose tissue of H-PGDS TG mice,
      transcription levels of peroxisome proliferator-activated receptor gamma, fatty
      acid binding protein 4 and lipoprotein lipase were increased approximately two
      fold to five-fold as compared with those of WT mice. Finally, H-PGDS TG mice
      showed clear hypoglycemia after insulin clamp. These results indicate that TG
      mice overexpressing H-PGDS abundantly produced PGD(2) in adipose tissues,
      resulting in pronounced adipogenesis and increased insulin sensitivity. The
      present study provides the first evidence that PGD(2) participates in the
      differentiation of adipocytes and in insulin sensitivity in vivo, and the H-PGDS
      TG mice could constitute a novel model mouse for diabetes studies.

PMID- 20136656
TI  - CrkL is a novel target of Sprouty2 in fibroblast growth factor signaling.
AB  - Sprouty, an inhibitor of receptor tyrosine kinase signaling, plays an important
      role in the regulation of a wide variety of biological processes. Although it is
      established that the Sprouty inhibitory activity is induced by tyrosine
      phosphorylation in response to stimuli, its action mechanisms have not been fully
      elucidated. Here, we report identification of a novel target of Sprouty. We find
      that Sprouty1 and Sprouty2 bind to the adaptor protein CrkL in a stimulus
      dependent manner. Biochemical analyses show that the binding requires tyrosine
      phosphorylation of Sprouty and that both the SH2 domain and the N-terminal SH3
      domain of CrkL are necessary for the binding. In fibroblast growth factor
      stimulated NIH3T3 cells, CrkL binding to Sprouty2 occurs concomitantly with
      tyrosine phosphorylation of Sprouty2, which occurs slowly but is sustained.
      Importantly, our results show that tyrosine-phosphorylated Sprouty2 suppresses
      Rap1 activation. These results taken together indicate that Sprouty2 acts as an
      inhibitor of CrkL-Rap1 signaling. 

PMID- 20136657
TI  - Knowledge of disease and adherence in adult patients with haemophilia.
AB  - Patients with moderate and severe haemophilia are evaluated on a regular basis at
      their haemophilia centres but patients with mild haemophilia are seen less often
      because of fewer problems related to their disease. The needs of patients with
      milder forms of haemophilia, however, are often underestimated, both by the
      patient and staff at healthcare facilities. This study evaluated the knowledge of
      disease and adherence to treatment among patients with severe, moderate and mild
      haemophilia. This was a prospective multicentre study performed in Haemophilia
      Centres in Scandinavia. A total of 413 (67%) of 612 patients aged >25 years with
      mild, moderate and severe haemophilia completed a self-administered
      questionnaire. The mean age of the respondents was 49.7 years (range 25-87
      years). Of the 413 respondents, 150 had a mild, 86 had a moderate and 177 had a
      severe form of haemophilia. A total of 22 (5%) patients did not know the severity
      of their disease, and 230 (56%) patients knew the effect of factor concentrate in
      the blood. Of the 413 respondents, 53 (13%) of the cohort never treated a
      haemorrhage. Patients with mild haemophilia, P </= 0.001, were the least likely
      to treat a haemorrhage. The relative number of patients who were afraid of virus
      transmission by factor concentrate was about similar in the three groups, 27% of
      those with severe haemophilia, 26% with moderate and 24% with mild haemophilia.
      This study shows that the amount of knowledge among haemophilia patients about
      their disease and treatment is somewhat limited, and demonstrates the importance
      of continually providing information about haemophilia and treatment, especially
      to patients with a mild form of the disease.

PMID- 20136658
TI  - HIV and people over 50 years old in Europe.
AB  - OBJECTIVE: The aim of the study was to report on HIV and older people in the
      European Region, including new data stratified by subregion and year. METHODS:
      Data were collected from the 2008 World Health Organization Regional Office for
      Europe, Communicable Diseases Unit survey on HIV/AIDS and health systems.
      RESULTS: It was found that 12.9% of newly reported cases of HIV infection in
      Western Europe in 2007 were in people aged 50 years or older. In Central Europe,
      almost one-in-10 newly reported cases of HIV infection were in older people,
      while the proportion in Eastern Europe was 3.7% in 2007. CONCLUSIONS: The issue
      of HIV infection among older people is of increasing concern as more people age
      with HIV infection as a result of the availability of combination antiretroviral
      therapy.

PMID- 20136659
TI  - Definitions of antiretroviral treatment failure for measuring quality outcomes.
AB  - OBJECTIVES: Our aim was to compare three different definitions of treatment
      failure and discuss their use as quality outcome measures for a clinical service.
      METHODS: Data for treatment-naive patients who attended the Melbourne Sexual
      Health Centre (MSHC) between 1 January 2000 and 31 December 2008 were analysed.
      Definition 1 was the strict Food and Drug Administration (FDA) definition of
      treatment failure as determined using the time to loss of virological response
      (TLOVR) algorithm. Definition 2 defined treatment failure as occurring in those
      whose viral load never fell to <400 HIV-1 RNA copies/mL or who developed two
      consecutive viral loads > or =400 copies/mL on any treatment (switching or
      stopping treatment with a viral load <400 copies/mL was permitted). Definition 3
      was the same as definition 2 except that individuals were also deemed to have
      failed if they stopped treatment for 6 months or longer. RESULTS: There were 310
      antiretroviral-naive patients who started treatment in the study period. Of
      these, 156 [50.3%; 95% confidence interval (CI) 42.1-53.3%] experienced treatment
      failure under definition 1, 10 (3.2%; 95% CI 1.5-5.8%) experienced treatment
      failure under definition 2, and 16 (4.5%; 95% CI 2.5-7.4%) experienced treatment
      failure under definition 3 over the 108 months of follow-up. The probability of
      failing definition 1 was statistically different from the probability of failing
      definition 2 or 3 (P=0.01). CONCLUSION: There were significant differences in
      treatment failure for the three definitions. If definition 1 were used, the
      outcomes would be sufficiently common to enable clinics to be compared but would
      be less meaningful. If definition 2 or 3 were used, the events would be too rare
      to enable clinics to be compared, but it would be possible to set a benchmark
      level of success that clinics could aim to reach.

PMID- 20136660
TI  - Increasing HIV transmission through male homosexual and heterosexual contact in
      Australia: results from an extended back-projection approach.
AB  - OBJECTIVES: The aim of the study was to reconstruct the HIV epidemic in Australia
      for selected populations categorized by exposure route; namely, transmission
      among men who have sex with men (MSM), transmission among injecting drug users
      (IDUs), and transmission among heterosexual men and women in Australia. DESIGN:
      Statistical back-projection techniques were extended to reconstruct the
      historical HIV infection curve using surveillance data. Methods We developed and
      used a novel modified back-projection modelling technique that makes maximal use
      of all available surveillance data sources in Australia, namely, (1) newly
      diagnosed HIV infections, (2) newly acquired HIV infections and (3) AIDS
      diagnoses. RESULTS: The analyses suggest a peak HIV incidence in Australian MSM
      of approximately 2000 new infections per year in the late 1980s, followed by a
      rapid decline to a low of <500 in the early 1990s. We estimate that, by 2007,
      cumulatively approximately 20 000 MSM were infected with HIV, of whom 13% were
      not diagnosed with HIV infection. Similarly, a total of approximately 1050 and
      approximately 2600 individuals were infected through sharing needles and
      heterosexual contact, respectively, and in 12% and 23% of these individuals,
      respectively, the infection remained undetected. DISCUSSION: Male homosexual
      contact accounts for the majority of new HIV infections in Australia. However,
      the transmission route distribution of new HIV infections has changed over time.
      The number of HIV infections is increasing substantially among MSM, increasing
      moderately in those infected via heterosexual exposure, and decreasing in IDUs.

PMID- 20136662
TI  - Molecular characterization of two novel milk proteins in the tsetse fly (Glossina
      morsitans morsitans).
AB  - PURPOSE: Milk proteins are an essential component of viviparous reproduction in
      the tsetse fly. Milk proteins are synthesized in and secreted from the milk gland
      tissue and constitute 50% of the secretions from which the intrauterine larva
      derives its nourishment. To understand milk protein function and regulation
      during viviparous reproduction, milk proteins need to be identified and
      characterized. METHODS: Two putative unknown secretory proteins (GmmMGP2 and
      GmmMGP3) were selected by bioinformatic analysis of tissue specific tsetse cDNA
      libraries. RT-PCR analysis was performed to verify their milk gland/fat body
      specific expression profile. Detailed characterization of developmental and
      tissue specific expression of these proteins was performed by northern blot
      analysis and fluorescent in situ hybridization. Functional analysis of the milk
      gland proteins during the tsetse gonotrophic cycle was performed using RNA
      interference (RNAi). RESULTS: The predicted proteins from gmmmgp2 and gmmmgp3 are
      small approximately 22 kD and contain a high proportion of hydrophobic amino
      acids and potential phosphorylation sites. Expression of both genes is tissue
      specific to the secretory cells of the milk gland. Transcript abundance for both
      genes increases over the course of intrauterine larval development and parallels
      that of gmmmgp, a well characterized milk protein gene considered to be the major
      milk protein. Phenotypic analysis of flies after RNA interference treatment
      revealed a significant effect upon fecundity in the gmmmgp2 knockdown flies, but
      not the gmmmgp3 flies. Knockdown of gmmmgp2 resulted in disruption of ovulation
      and consequent oocyte accumulation and degradation. Gmmmgp2 knockdown also had a
      significant impact on fly mortality. CONCLUSIONS: This work identifies two novel
      genes, the proteins of which appear to function in response to intrauterine
      larvigenesis in tsetse. These proteins may be nutritional components of the milk
      secretions provided to the larva from the mother. Phenotypic data from knockdown
      of gmmmgp2 suggests that this protein may also have a regulatory function given
      the defect in ovulation observed in knockdown flies. Further analysis of these
      genes will be important (in conjunction with other milk proteins) for
      identification of transcriptional regulation mechanisms that direct milk
      gland/pregnancy specific gene expression.

PMID- 20136666
TI  - The nasolacrimal duct of anuran amphibians: suggestions on its functional role in
      vomeronasal perception.
AB  - Tear secretions discharged by the Harderian gland are suggested to function as a
      solvent for molecules sensed by the vomeronasal organ (VNO) in anurans. It has
      been assumed that chemical stimuli are absorbed at the surface of the eye to be
      carried - together with the lacrimal fluid - into the nasal cavity via the
      nasolacrimal duct. In the study presented herein, we examined the intranasal
      anatomy of 10 different anuran species to analyse the opening region of the
      nasolacrimal duct and its functional relationship with the VNO and the external
      naris. In addition, vital staining of the nasal cavities was conducted. Our
      results indicate that stimuli reaching the VNO are more likely to be ingested
      through the nostril than via the eye. In many cases the intranasal orifice of the
      nasolacrimal duct shows a close proximity to the external naris and
      simultaneously we observed a noticeable distance to the VNO. We suggest that the
      secretions of the Harderian gland are carried to the external naris by the
      nasolacrimal duct, where they bind chemical stimuli that are subsequently
      actively transported into the VNO. In some of the investigated species the
      opening region of the tear duct was situated in a more caudal part of the nasal
      cavity and closer to the VNO. In these cases a conspicuous system of channels can
      be found, which is suspected to carry the intruding medium of smell from the
      nostril to the nasolacrimal aperture.

PMID- 20136661
TI  - Nevirapine/zidovudine/lamivudine has superior immunological and virological
      responses not reflected in clinical outcomes in a 48-week randomized comparison
      with abacavir/zidovudine/lamivudine in HIV-infected Ugandan adults with low CD4
      cell counts.
AB  - BACKGROUND: Triple nucleoside reverse transcriptase inhibitor regimens have
      advantages as first-line antiretroviral therapy (ART), avoiding hepatotoxicity
      and interactions with anti-tuberculosis therapy, and sparing two drug classes for
      second-line ART. Concerns exist about virological potency; efficacy has not been
      assessed in Africa. METHODS: A safety trial comparing nevirapine with abacavir
      was conducted in two Ugandan Development of Antiretroviral Therapy in Africa
      (DART) centres: 600 symptomatic antiretroviral-naive HIV-infected adults with CD4
      counts <200 cells/microL were randomized to zidovudine/lamivudine plus abacavir
      or nevirapine (placebo-controlled to 24-week primary toxicity endpoint, and then
      open-label). Documented World Health Organization (WHO) stage 4 events were
      independently reviewed and plasma HIV-1 RNA assayed retrospectively. Exploratory
      efficacy analyses are intention-to-treat. RESULTS: The median pre-ART CD4 count
      was 99 cells/microL, and the median pre-ART viral load was 284 600 HIV-1 RNA
      copies/mL. A total of 563 participants (94%) completed 48 weeks of follow-up, 25
      (4%) died and 12 (2%) were lost to follow-up. The randomized drug was substituted
      in 21 participants (7%) receiving abacavir vs. 34 (11%) receiving nevirapine
      (P=0.09). At 48 weeks, 62% of participants receiving abacavir vs. 77% of those
      receiving nevirapine had viral loads <50 copies/mL (P<0.001), and mean CD4 count
      increases from baseline were +147 vs. +173 cells/microL, respectively (P=0.006).
      Nine participants (3%) receiving abacavir vs. 16 (5%) receiving nevirapine died
      [hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.24-1.25; P=0.15]; 20
      receiving abacavir vs. 32 receiving nevirapine developed new or recurrent WHO 4
      events or died (HR=0.60; 95% CI 0.34-1.05; P=0.07) and 48 receiving abacavir vs.
      68 receiving nevirapine developed new or recurrent WHO 3 or 4 events or died
      (HR=0.67; 95% CI 0.46-0.96; P=0.03). Seventy-one participants (24%) receiving
      abacavir experienced 91 grade 4 adverse events compared with 130 events in 109
      participants (36%) on nevirapine (P<0.001). CONCLUSIONS: The clear
      virological/immunological superiority of nevirapine over abacavir was not
      reflected in clinical outcomes over 48 weeks. The inability of CD4 cell
      count/viral load to predict initial clinical treatment efficacy is unexplained
      and requires further evaluation.

PMID- 20136667
TI  - Redistribution of nuclear pores during formation of the redundant nuclear
      envelope in mouse spermatids.
AB  - Extensive morphological modification occurs during mammalian spermiogenesis when
      spermatids change their spherical shape into cells with a compact head and a long
      tail. In this study, freeze-fracture was used to elucidate the alteration of the
      nuclear envelope during this process. Nuclear condensation resulted in a great
      reduction of spermatid nuclear volume and the formation of the redundant nuclear
      envelope. During nuclear condensation, distribution patterns of nuclear pores
      were greatly affected by the developing acrosome and manchette. As the acrosome
      enlarged to cap the nucleus, the pores redistributed caudally in the nuclear
      membranes and became exclusively localized to the redundant nuclear envelope.
      Manchette microtubules play an important role in shaping the nucleus, and
      formation of the manchette was associated with exclusion of nuclear pores from
      the underlying nuclear envelope; therefore, it is likely that the redistribution
      of nuclear pores was aided by manchette development. The appearance of an
      electron-lucent nuclear region surrounded by the nascent redundant nuclear
      envelope indicated a pathway for transporting degradation products through the
      nuclear pores to the residual cytoplasm. The packaging of the nuclear pores into
      the redundant nuclear envelope suggests that they play a role in late stages of
      sperm maturation or in fertilization, as most other unnecessary organelles of
      sperm are discarded during spermiogenesis or during shedding of the cytoplasmic
      droplet.

PMID- 20136668
TI  - Somatotopic organization of lumbar muscle-innervating neurons in the ventral horn
      of the rat spinal cord.
AB  - The ventral horn of the rat spinal cord was investigated with respect to the
      somatotopic organization of the motor neurons that innervate the lumbar muscles.
      Neurotracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate
      (DiI) was applied to specific sites in lumbar muscles. Spinal cord segments at L1
      through L4 levels were cut into 40-mum serial transverse sections. Labeled
      neurons were located in the ventromedial nucleus (VM) and lateromedial nucleus
      (LM) nuclei of Rexed's lamina IX. Motor neurons innervating the m. interspinales
      lumborum and m. multifidus were without exception present in the VM, whereas all
      motor neurons innervating the m. rectus abdominis were present in the LM. Forty
      percent of motor neurons innervating the m. quadratus lumborum were present in
      the VM and the other 60% were in the LM. Although most of the motor neurons
      innervating the m. psoas major were present in the LM, a few labeled neurons
      existed in the VM. These results suggest that the border zone demarcating the
      areas of innervation of the dorsal and ventral rami of spinal nerves crosses the
      m. quadratus lumborum.

PMID- 20136669
TI  - Somitic origin of the medial border of the mammalian scapula and its homology to
      the avian scapula blade.
AB  - The scapula is the main skeletal element of the pectoral girdle allowing muscular
      fixation of the forelimb to the axial skeleton. The vertebrate limb skeleton has
      traditionally been considered to develop from the lateral plate mesoderm, whereas
      the musculature originates from the axial somites. However, in birds, the
      scapular blade has been shown to develop from the somites. We investigated
      whether a somitic contribution was also present in the mammalian scapula. Using
      genetic lineage-tracing techniques, we show that the medial border of the
      mammalian scapula develops from somitic cells. The medial scapula border serves
      as the attachment site of girdle muscles (serratus anterior, rhomboidei and
      levator scapulae). We show that the development of these muscles is independent
      of the mechanism that controls the formation of all other limb muscles. We
      suggest that these muscles be specifically referred to as medial girdle muscles.
      Our results establish the avian scapular blade and medial border of the mammalian
      scapula as homologous structures as they share the same developmental origin.

PMID- 20136670
TI  - Structural analysis of the human tibia by tomographic (pQCT) serial scans.
AB  - This study analyses the evaluation of tomographic indicators of tibia structure,
      assuming that the usual loading pattern shifts from uniaxial compression close to
      the heel to a combined compression, torsion and bending scheme towards the knee.
      To this end, pQCT scans were obtained at 5% intervals of the tibia length (S5-S95
      sites from heel to knee) in healthy men and women (10/10) aged 20-40 years.
      Indicators of bone mass [cortical area, cortical/total bone mineral content
      (BMC)], diaphyseal design (peri/endosteal perimeters, cortical thickness,
      circularity, bending/torsion moments of inertia - CSMIs), and material quality
      [(cortical vBMD (bone mineral density)] were determined. The longitudinal
      patterns of variation of these measures were similar between genders, but male
      values were always higher except for cortical vBMD. Expression of BMC data as
      percentages of the minimal values obtained along the bone eliminated those
      differences. The correlative variations in cortical area, BMC and thickness,
      periosteal perimeter and CSMIs along the bone showed that cortical bone mass was
      predominantly associated with cortical thickness toward the mid-diaphysis, and
      with bone diameter and CSMIs moving more proximally. Positive relationships
      between CSMIs (y) and total BMC (x) showed men's values shifting to the upper
      right region of the graph and women's values shifting to the lower-left region.
      Total BMC decayed about 33% from S5 to S15 (where minimum total BMC and CSMI
      values and variances and maximum circularity were observed) and increased until
      S45, reaching the original S5 value at S40. The observed gender-related
      differences reflected the natural allometric relationships. However, the data
      also suggested that men distribute their available cortical mass more efficiently
      than women. The minimum amount and variance of mass indicators and CSMIs, and the
      largest circularity observed at S15 reflected the assumed adaptation to
      compression pattern at that level. The increase in CSMIs (successively for
      torsion, A-P bending, and lateral bending), the decrease in circularity values
      and the changes in cortical thickness and periosteal perimeter toward the knee
      described the progressive adaptation to increasing torsion and bending stresses.
      In agreement with the biomechanical background, the described relationships: (i)
      identify the sites at which some changes in tibial stresses and diaphyseal
      structure take place, possibly associated with fracture incidence; (ii) allow
      prediction of mass indicators at any site from single determinations; (iii)
      establish the proportionality between the total bone mass at regions with highly
      predominant trabecular and cortical bone of the same individual, suitable for a
      specific evaluation of changes in trabecular mass; and (iv) evaluate the ability
      of bone tissue to self-distribute the available cortical bone according to
      specific stress patterns, avoiding many anthropometric and gender-derived
      influences.

PMID- 20136671
TI  - Suggestive evidence of a vesicle-mediated mode of cell degranulation in
      chromaffin cells. A high-resolution scanning electron microscopy investigation.
AB  - In this study we used a modified osmium maceration method for high-resolution
      scanning electron microscopy to study some ultrastructural details fitting the
      schema of piecemeal degranulation in chromaffin cells. Piecemeal degranulation
      refers to a particulate pattern of cell secretion that is accomplished by vesicle
      mediated extracellular transport of granule-stored material. We investigated
      adrenal samples from control and angiotensin II-treated rats, and identified a
      variable proportion of smooth, 30-60-nm-diameter vesicles in the cytoplasm of
      chromaffin cells. A percentage of these vesicles were interspersed in the cytosol
      among chromaffin granules but the majority appeared to be attached to granules.
      Remarkably, the number of unattached cytoplasmic vesicles was greatly increased
      in chromaffin cells from angiotensin II-treated animals. Vesicles of the same
      structure and dimension were detected close to or attached to the cytoplasmic
      face of the plasma membrane; these, too, were increased in number in chromaffin
      cells from rats stimulated with angiotensin II. In specimens shaken with a
      rotating agitator during maceration, the cytoplasmic organelles could be
      partially removed and the fine structure of the vesicular interaction with the
      inner side of the plasma membrane emerged most clearly. A proportion of
      chromaffin granules showed protrusions that we interpreted as vesicular
      structures budding from the granular envelope. In some instances, the transection
      plane intersected granules with putative vesicles emerging from the surfaces. In
      these cases, the protrusions of budding vesicles could be observed from the
      internal side. This study provides high-resolution scanning electron microscopy
      images compatible with a vesicle-mediated degranulation mode of cell secretion in
      adrenal chromaffin cells. The data indicating an increase in the number of
      vesicles observed in chromaffin cells after stimulation with the chromaffin cell
      secretagogue angiotensin II suggests that this secretory process may be
      susceptible to fine regulation.

PMID- 20136672
TI  - Successful surgical repair of tricuspid valve endocarditis.
AB  - Surgical treatment of tricuspid valve endocarditis is challenging especially in
      intravenous drug users. We present a case of a 30-year-old male active drug user
      with anterior leaflet endocarditis treated successfully with valve repair. This
      was achieved through excision of the vegetation with part of the leaflet. Bovine
      pericardium was used to close the defect. The edges were reinforced with Teflon
      pledgeted polytetrafluoroethylene Gore-Tex neochordae (W.L. Gore & Associates,
      Flagstaff, AZ, USA). An annuloplasty ring was used to reinforce the whole
      annulus. Repair was competent and the patient recovered well. This technique is
      simple and effective and should be considered for similar cases.

PMID- 20136673
TI  - Aortic rupture in a heart transplant patient following recent blunt aortic
      trauma.
AB  - We report a case of a patient who developed an aortic dissection with rupture.
      This presumably was a delayed injury following blunt thoracic trauma and
      highlights that concerns for aortic pathology even in this patient population.

PMID- 20136674
TI  - Photodynamic therapy in dermatology.
AB  - Photodynamic therapy (PDT) is a modern therapy modality, based upon the
      application of a photosensitizing agent like aminolevulinic acid, a physiological
      precursor of porphyrins, onto the tissue followed by illumination with light of
      the visible wavelength spectrum. During this oxygen-dependent reaction, reactive
      oxygen species (ROS) are generated that have immunomodulatory or cytotoxic
      effects. PDT shows excellent cosmetic results especially for its key indication
      in dermatology - the treatment of non-melanoma skin cancer. The associated pain
      and the low tissue penetration are the most frequent limiting factors of PDT. We
      review basic principles and recent developments in photosensitizers and light
      sources. Key oncological and non-oncological indications are presented as well.

PMID- 20136675
TI  - [Histamine as an immunomodulator].
AB  - The role of histamine as an important proinflammatory mediator has been well
      known for nearly 100 years. In regards to the immediate type allergic response,
      there is no debate about the importance of histamine. In addition, histamine has
      immunomodulatory functions, some of which are related to the histamine H2
      receptor. However, with the discovery of the histamine H(4) receptor in the year
      2000, the role of histamine as an immunomodulator became more obvious. The
      histamine H(4) receptor is expressed on several hematopoietic cells; along with
      the chemotaxis of immune cells, this recently characterized receptor modulates
      also the cytokine and chemokine secretion of some hematopoietic cells. Highly
      selective histamine H(4) receptor antagonists display promising results in animal
      models of allergic inflammatory diseases and also in in vitro studies on animal
      and human cells. These first results indicate that the histamine H(4) receptor is
      an interesting new pharmacological target for the treatment of allergic
      inflammatory disorders. This review summarizes the most important
      immunomodulatory functions of histamine and points to some possible indications
      in dermatology.

PMID- 20136676
TI  - Adverse drug reactions to biologics.
AB  - The use of biologics has rapidly expanded since the introduction of the first
      diagnostic antibodies; they are now widely employed in oncology, autoimmune
      disorders, inflammatory diseases and transplantation medicine. Their widespread
      use has resulted in an increase in adverse drug reactions. Adverse effects result
      from both direct pharmacological actions and immunological actions, as well as
      through induction of a specific immune response. The nomenclature, particularly
      of the monoclonal antibodies, identifies the target structure and organ as well
      as the species of origin, which then helps predict their effects and antigenic
      properties. Depending on the extent of foreign protein, anti-allotypic or anti
      idiotypic antibodies with or without neutralizing properties may be induced.
      Adverse drug reactions from biologics often depend on the target and may be
      explained by activation or inhibition of particular cytokine pathways. Adverse
      drug reactions are classified by their pathomechanism, which enhances
      understanding of the pathogenesis and facilitates both allergologic diagnostic
      measures and planning of premedication in future treatments. This review
      emphasizes immunostimulatory and hypersensitivity reactions.

PMID- 20136677
TI  - Effects of camel thorn distillate on recurrent oral aphthous lesions.
AB  - BACKGROUND: Near 20 % of people suffer from recurrent oral aphthous ulcers. These
      painful ulcers are found on the oral mucosa. We conducted this study to evaluate
      the effect of the camel thorn distillate on this condition. PATIENTS AND METHODS:
      93 patients with recurrent aphthous ulcers were selected and divided into two
      groups. One group was given a placebo (n = 44) and the other was given camel
      thorn distillate (n = 49). The diameter of the lesions and the severity of the
      pain were measured 3, 5, 7, 10 and 14 days after initiation of therapy. The
      lesion diameters and pain scores of the two groups were compared using the t
      test. RESULTS: Complete resolution time ranged from 3 to 7 days (mean = 4.02) in
      the group treated with camel thorn distillate, whereas in the control group,
      complete resolution time ranged from 7 to 14 days (mean = 8.9, p < 0.001).
      CONCLUSIONS: The efficacy of camel thorn distillate is comparable to that of
      other drugs used to treat oral aphthous ulcers. Its therapeutic effect may be due
      to the flavanones (alhagitin and alhagidin) that are present in this plant.

PMID- 20136678
TI  - A novel two-step kit for topical treatment of tinea pedis--an open study.
AB  - BACKGROUND: Tinea pedis is a common skin disease affecting most of the population
      during their lifetime. Topical and systemic treatments give only temporary
      relief. OBJECTIVE: To evaluate the efficacy and safety of a new topical treatment
      for moderate-to-severe tinea pedis. METHODS: Fifty patients suffering from tinea
      pedis were treated in two stages: the active stage--single use of the novel
      topical solution for 45 min and novel cream twice weekly for 4 weeks; the
      preventive stage--cream application once weekly for 10 months. RESULTS: Forty
      five patients completed the active stage and achieved 76% cure rate. The
      medication was well tolerated; one patient dropped from the study because of very
      mild irritation. No other topical or systemic side effects were noted. Another
      five patients were lost to follow-up during the preventive stage. The total cure
      rate after the preventive stage was 70%. CONCLUSIONS: This novel treatment was
      found to be effective, well tolerated and safe in the treatment of moderate and
      severe tinea pedis during the active and the preventive stages.

PMID- 20136679
TI  - Fibrosing alopecia in a pattern distribution.

PMID- 20136680
TI  - Relationships between obesity and the clinical severity of psoriasis in Taiwan.
AB  - BACKGROUND: Obesity has been found to be associated with an increased risk of
      psoriasis in general population. However, studies addressing the relationship
      between obesity and clinical severity of psoriasis are still scarce, especially
      in Asian people. OBJECTIVES: In this study, we investigated the relationship
      between levels of obesity and the clinical severity of psoriasis in Taiwanese
      psoriasis patients. METHODS: This was a hospital-based cross-sectional study. A
      total of 399 patients with chronic plaque psoriasis were recruited. Their body
      mass index (BMI) was calculated as weight in kilograms divided by height in
      metres squared and was categorized into four groups (BMI < 24, normal; 24 <or=
      BMI < 27, overweight; 27 <or= BMI < 30, mild obesity; and BMI >or= 30, moderate
      to-severe obesity). Disease severity was assessed by Psoriasis Area and Severity
      Index. Cumulative logistic regression models were used to estimate the
      association between BMI and Psoriasis Area and Severity Index. RESULTS: After
      adjusting for potential confounders (age, gender, cigarette smoking and duration
      of disease), moderate-to-severe obesity was significantly associated with an
      increased risk of clinically more severe psoriasis when compared with normal BMI
      [odds ratio, 2.70; 95% confidence interval,1.42-5.11]. There is a significant
      linear trend for clinically more severe psoriasis across increasing of BMI
      categories (P for trend = 0.004). The effect of obesity on the severity of
      psoriasis was greater in men than in women (test for interaction, P = 0.03).
      CONCLUSIONS: In psoriasis patients, obesity is associated with a more severe
      disease, especially in men. Bodyweight control may be important for the
      management of psoriasis.

PMID- 20136681
TI  - Understanding early communication signals in autism: a study of the perception of
      infants' cry.
AB  - BACKGROUND: Previous studies have highlighted that episodes of crying of children
      with autistic disorder (AD) were perceived as inexplicable from their parents who
      could not identify causative factors. These results supported the view of AD as
      related to a problem of expressing and sharing emotions. Moreover, no evidence
      has been presented on which characteristics of a cry episode influence the adult
      perception. Aim of our research is to investigate how acoustical features of
      crying episodes modulate their perception of infants with ASD compared with
      infants with typical development (TD) and infants with developmental delay (DD).
      METHODS: Two studies were employed. In study 1, we artificially modified
      structural parameters (fundamental frequency, duration of the pauses, waveform
      modulation) of a cry episode, and then 50 adults (parents and non-parents) were
      asked to judge the level of distress elicited. In study 2, acoustic analysis was
      applied to episodes of crying selected from retrospective home videos of 42
      children with AD, TD and DD at 18 months. RESULTS: The results showed that (1)
      differences in the fundamental frequency and in other structural parameters of
      the cry lead parents and non-parents to perceive an episode of crying as more
      aversive and (2) at 18 months of age, AD episodes of crying have higher
      fundamental frequency (f0). CONCLUSION: Our findings offer support for the
      hypothesis that acoustic characteristics of episodes of crying of children with
      autism, especially higher fundamental frequencies, may account for mental states
      of uneasiness in the listener.

PMID- 20136682
TI  - Personality disorders in offenders with intellectual disability: a comparison of
      clinical, forensic and outcome variables and implications for service provision.
AB  - AIM: To establish any differences between patients with and without a diagnosis
      of personality disorders, being treated in a secure inpatient service for
      offenders with intellectual disability (ID) in the UK. METHOD: A cohort study
      involving a selected population of people with ID and offending behaviours.
      Results The study included a total of 138 patients, treated over a 6 year period 
      77 with a dissocial or emotionally unstable personality disorder and 61 without.
      Women were more likely to be in the personality disorder group. Both groups had
      high prevalence of abuse with no significant differences. Depressive disorders
      and substance abuse were more common in the personality disorder group, while
      epilepsy and autistic spectrum disorders were more common in the non-personality
      disorder group. Rather than differences, what was more striking was the rate and
      range of these comorbidities across both groups. Although past histories of
      violence and institutional aggression were no different, compulsory detention
      under criminal sections and restriction orders were more common in the
      personality disorder group. There were no differences in treatment outcomes.
      CONCLUSIONS: Although about half of patients detained in secure units for
      offenders with ID have a personality disorder, there were more similarities than
      differences between this group and the rest. While good treatment outcomes
      supported the case for specialised secure treatment units for people with ID, the
      case for establishing a more specialised ID-personality disorder unit was less
      convincing. There is also a need to explore whether there are alternative
      diagnostic models that can delineate better the group with personality
      difficulties in this population.

PMID- 20136683
TI  - Cognitive profile in a large French cohort of adults with Prader-Willi syndrome:
      differences between genotypes.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic disorder characterised
      by developmental abnormalities leading to somatic and psychological symptoms.
      These include dysmorphic features, impaired growth and sexual maturation,
      hyperphagia, intellectual delay, learning disabilities and maladaptive
      behaviours. PWS is caused by a lack of expression of maternally imprinted genes
      situated in the 15q11-13 chromosome region. The origin is a 'de novo' deletion in
      the paternal chromosome in 70% of the cases and a maternal uniparental disomy in
      25%. The two main genotypes show differences, notably regarding cognitive and
      behavioural features, but the mechanisms are not clear. This study assessed
      cognitive impairment in a cohort of adults with genetically confirmed PWS,
      analysed their profiles of cognitive strengths and weaknesses, and compared the
      profiles in terms of genotype. METHODS: Ninety-nine male and female adults
      participated, all inpatients on a specialised unit for the multidisciplinary care
      of PWS. The Wechsler Adult Intelligence Scale (WAIS-III) was administered to all
      patients in identical conditions by the same psychologist. Eighty-five patients
      were able to cope with the test situation. Their scores were analysed with non
      parametric statistical tools. The correlations with sex, age and body mass index
      were explored. Two genotype groups were compared: deletion (n = 57) and non
      deletion (n = 27). RESULTS: The distribution of intelligence quotients in the
      total cohort was non-normal, with the following values (medians): Full Scale
      Intelligence Quotient (FSIQ): 52.0 (Q1:46.0; Q3:60.0), Verbal Intellectual
      Quotient (VIQ): 53.0 (Q1:48; Q3:62) and Performance Intellectual Quotient (PIQ):
      52.5 (Q1:48; Q3:61). No correlation was found with sex, age or body mass index.
      Comparison between groups showed no significant difference in FSIQ or VIQ. PIQ
      scores were significantly better in the deletion group. The total cohort and the
      deletion group showed the VIQ = PIQ profile, whereas VIQ > PIQ was observed in
      the non-deletion group. The subtest scores in the two groups showed significant
      differences, with the deletion group scoring better in three subtests: object
      assembly, picture arrangement and digit symbol coding. Some relative strengths
      and weaknesses concerned the total cohort, but others concerned only one
      genotype. DISCUSSION: We documented a global impairment in the intellectual
      abilities of a large sample of French PWS patients. The scores were slightly
      lower than those reported in most other studies. Our data confirmed the
      previously published differences in the cognitive profiles of the two main PWS
      genotypes and offer new evidence to support this hypothesis. These results could
      guide future neuropsychological studies to determine the cognitive processing in
      PWS. This knowledge is essential to improve our understanding of gene-brain
      behaviour relationships and to open new perspectives on therapeutic and
      educational programmes.

PMID- 20136684
TI  - An exploratory study of the defence mechanisms used in psychotherapy by adults
      who have intellectual disabilities.
AB  - PROBLEM: A significant concept in psychodynamic theory and practice is that of
      defence mechanisms. The identifications of defences is a key task of the
      therapist and these are then used in the formulation and form part of the
      therapist's interventions. Case studies of psychotherapy with adults who have
      intellectual disabilities (IDs) suggest that they use more primitive defences but
      this has not been empirically evaluated. This study aimed to find out what
      defences adults with IDs use within and across sessions of individual
      psychotherapy. METHODS: Transcripts of psychotherapy sessions with a case series
      of eight adults with IDs were evaluated using the defence mechanism rating scale.
      RESULTS: Contrary to expectation the participants were observed to use a wide
      range of defences from primitive to mature. There was evidence to suggest that
      participants had developed a defensive style, but little evidence to show change
      in defensive structure across the first eight sessions of treatment. CONCLUSIONS:
      This exploratory study shows that adults who have IDs use a range of defences in
      psychotherapy and have particular defensive styles. The results suggest that
      future studies may need more participants and a longer time frame to see if
      change in defences occurs during psychotherapy. The defence mechanism rating
      scale may also need some validation work with adults who have IDs and consider
      inclusion of some defences that are disability-specific.

PMID- 20136685
TI  - Pregnancy decreases oestrogen receptor alpha expression and pyknosis, but not
      cell proliferation or survival, in the hippocampus.
AB  - Motherhood differentially affects learning and memory performance and this effect
      depends on reproductive experience. In turn, evidence suggests that the effects
      of oestradiol on learning and memory are mediated through binding to oestrogen
      receptors in the hippocampus and that this is related to hippocampal
      neurogenesis. The present study investigated the effect of pregnancy and
      reproductive experience on ERalpha expression throughout the hippocampus, as well
      as cell proliferation, new cell survival and cell death (as measured by pyknotic
      cells) in the granule cell layer of the hippocampus. Three groups of female
      Sprague-Dawley rats were used: virgin, primigravid and multigravid. All rats were
      injected with 5-bromo-2-deoxyuridine (BrdU; 200 mg/kg) on the afternoon of
      impregnation and at matched time-points in virgins. Rats were perfused either
      during early pregnancy (gestation day 1) or late pregnancy (gestation day 21)
      after BrdU injection. The results obtained show that, during late pregnancy,
      females, whether first or second pregnancy, have fewer ERalpha-positive cells in
      the CA3 region of the dorsal hippocampus than virgin females. In addition during
      early pregnancy, females have significantly fewer pyknotic cells in the granule
      cell layer than virgin females. There were no other differences between groups in
      the number of ERalpha-positive, BrdU-positive or pyknotic cells. Future studies
      will aim to investigate the mechanisms and consequences of the alteration in
      ERalpha expression in the hippocampus during late pregnancy, as well as the
      possible changes in ERbeta expression at this time.

PMID- 20136686
TI  - Inhibitory effect of prepro-thyrotrophin-releasing hormone (178-199) on
      adrenocorticotrophic hormone secretion by human corticotroph tumours.
AB  - Prepro-thyrotrophin-releasing hormone (TRH) (178-199), a 22-amino acid cleavage
      product of the TRH prohormone, has been postulated to act as an
      adrenocorticotrophin hormone (ACTH)-release inhibitor. Indeed, although in vitro
      evidence indicates that this peptide may inhibit basal and stimulated ACTH
      secretion in rodent anterior pituitary primary cultures and cell lines, not all
      studies concur and no study has as yet evaluated the effect of this peptide in
      Cushing's disease. The present study aimed to test the effect of preproTRH(178
      199) in human tumoural corticotrophs. Twenty-four human ACTH-secreting pituitary
      tumours (13 macroadenomas, 11 microadenomas) were collected during surgery and
      incubated with 10 or 100 nm preproTRH(178-199). ACTH secretion was assessed after
      4 and 24 h of incubation by immunometric assay and expressed relative to levels
      observed in control, unchallenged wells (= 100%). Parallel experiments were
      performed in rat anterior pituitary primary cultures. A clear inhibition of ACTH
      secretion at 4 and 24 h was observed in 12 specimens (for 10 nm ppTRH: 70 +/- 4%
      control at 4 h and 83 +/- 5% control at 24 h; for 100 nm ppTRH: 70 +/- 4% control
      at 4 h and 85 +/- 5% control at 24 h), whereas a mild and short-lasting
      stimulatory effect was observed in three tumours and no changes in ACTH secretion
      in the remaining nine tumoural specimens. The inhibitory effect of preproTRH(178
      199) was more evident in macroadenomas and significantly correlated with
      sensitivity to dexamethasone inhibition. Significant inhibition of ACTH secretion
      by preproTRH(178-199) in rat pituitary cultures was observed after 24 h of
      incubation. The present study conducted in a large series of human corticotroph
      tumours shows that preproTRH(178-199) inhibits tumoural ACTH secretion in a
      sizable proportion of specimens, in close relation to the size of the tumour and
      its sensitivity to glucocorticoid negative feedback. This appears a promising
      avenue of research and further studies are warranted to explore the full scope of
      preproTRH(178-199) as a regulator of ACTH secretion.

PMID- 20136687
TI  - Androgenic and oestrogenic influences on tyrosine hydroxylase-immunoreactive
      cells of the prairie vole medial amygdala and bed nucleus of the stria
      terminalis.
AB  - The posterodorsal medial amygdala (MeApd) and principal nucleus of the bed
      nucleus of the stria terminalis (pBST) are densely interconnected sites
      integrating steroid hormone and olfactory information necessary for sociosexual
      behaviours in many rodents. Our laboratory recently reported sexually dimorphic
      populations of cells containing tyrosine hydroxylase (TH) located in the MeApd
      and pBST of prairie voles (Microtus ochrogaster), with males having many more TH
      immunoreactive (-ir) cells in these sites than do females. Gonadal hormones
      circulating during adulthood were showm to regulate this sex difference because
      it was eliminated by castrating adult males or implanting females with
      testosterone-filled capsules. In the present study, we demonstrate that many (25
      65%) TH-ir cells in the MeApd and pBST of adult virgin male and female prairie
      voles also contain immunoreactivity for either the androgen receptor or oestrogen
      receptor alpha. Subcutaneous implants of oestradiol benzoate mimicked the effects
      of testosterone and maintained high numbers of TH-ir cells in these sites in
      castrated males. However, implants of dihydrotestosterone (DHT) did not, and
      these males had low numbers of TH-ir cells similar to castrated males given empty
      capsules. A similar effect was found in females, where testosterone or oestradiol
      benzoate greatly increased the number of TH-ir cells in these sites compared to
      intact or ovariectomised controls, but DHT did not. DHT implants did, however,
      maintain high seminal vesicle weights in males. Thus, many of the TH-ir cells in
      the prairie vole MeApd and pBST are potentially sensitive to androgens and
      oestrogens, although maintaining immunocytochemically detectable levels of TH in
      these cells may depend more on an oestrogen-mediated mechanism in both sexes.
      These data have implications for understanding how gonadal hormone release across
      the reproductive cycle modulates these species-specific groups of
      catecholaminergic cells and socially monogamous behaviours in prairie voles.

PMID- 20136688
TI  - Prenatal social stress in the rat programmes neuroendocrine and behavioural
      responses to stress in the adult offspring: sex-specific effects.
AB  - Stress exposure during pregnancy can 'programme' adult behaviour and hypothalamic
      pituitary-adrenal (HPA) axis stress responsiveness. In the present study, we
      utilised an ethologically relevant social stressor to model the type of stress
      that pregnant women may experience. We investigated the effects of social defeat
      by a resident lactating rat over 5 days during the last week of pregnancy on the
      pregnant intruder rat HPA axis, and on HPA responsivity to stress and anxiety
      related behaviour in the adult offspring of the socially-defeated intruder rats.
      HPA axis responses after social defeat were attenuated in the pregnant rats
      compared to virgin females. In the adult offspring, systemic interleukin (IL)
      1beta or restraint increased adrenocorticotrophic hormone and corticosterone
      secretion in male and female control rats; however, in prenatally stressed (PNS)
      offspring, HPA responses were greatly enhanced and peak hormone responses to IL
      1beta were greater in females versus males. Male PNS rats displayed increased
      anxiety behaviour on the elevated plus maze; however, despite marked changes in
      anxiety behaviour across the oestrous cycle, there were no differences between
      female control and PNS rats. Investigation of possible mechanisms showed
      mineralocorticoid mRNA levels were reduced in the hippocampus of male and female
      PNS offspring, whereas glucocorticoid receptor mRNA expression was modestly
      reduced in the CA2 hippocampal subfield in female PNS rats only. Corticotropin
      releasing hormone mRNA and glucocorticoid receptor mRNA expression in the central
      amygdala was greater in PNS males and females compared to controls. The data
      obtained in the present study indicate that prenatal social stress differentially
      programmes anxiety behaviour and HPA axis responses to stress in male and female
      offspring. Attenuated glucocorticoid feedback mechanisms in the limbic system may
      underlie HPA axis hyper-reactivity to stress in PNS offspring.

PMID- 20136689
TI  - Stimulus-specific neuroendocrine responses to osmotic challenges in apelin
      receptor knockout mice.
AB  - The expression of the novel peptide apelin and its receptor APJ within specific
      regions of the brain, in particular the magnocellular neurones of the
      hypothalamus and the circumventricular organs, has implicated the apelinergic
      system in mechanisms controlling fluid homeostasis. In addition, apelin and APJ
      are considered to be involved in controlling arginine vasopressin (AVP) secretion
      into the circulation and release within the hypothalamic-neurohypophysial system.
      To clarify the role of APJ during regulation of fluid homeostasis, we compared
      the effects of osmotic stimulation on the urinary concentrating capacities and
      central nervous system responses of salt-loaded (SL) and water-deprived (WD)
      female APJ knockout (APJ(-/-)) mice and wild-type controls. SL resulted in a
      significantly increased urine volume in APJ(-/-) mice compared to wild-type
      controls, whereas WD in APJ(-/-) mice failed to reduce urine volume as seen in
      wild-type controls. AVP transcripts in the supraoptic and paraventricular nuclei
      and plasma AVP concentrations were significantly attenuated in SL APJ(-/-) mice
      compared to SL wild-type, but increased comparably in wild-type and APJ(-/-) mice
      after WD. Analysis of c-fos mRNA expression in the median preoptic nucleus and
      subfornical organ in response to either WD or SL showed attenuated expression in
      APJ(-/-) compared to wild-type mice. These findings further implicate the
      apelinergic system in mechanisms controlling fluid homeostasis, particularly at a
      neuroendocrine level, and suggest stimulus-specific involvement in
      vasopressinergic activity.

PMID- 20136690
TI  - Neonatal programming by neuroimmune challenge: effects on responses and tolerance
      to septic doses of lipopolysaccharide in adult male and female rats.
AB  - A mild immune challenge experienced during the neonatal period leads to
      attenuated febrile responses to a similar challenge experienced later in life.
      However, the immune response to an endotoxin differs depending upon the severity
      of the challenge and it is not clear whether a neonatal immune challenge will
      also affect responses to a severe, potentially life-threatening stimulus, such as
      sepsis. In the present study, we examined the effects of a neonatal immune
      challenge with lipopolysaccharide (LPS) on adult sickness responses, as well as
      the development of endotoxin tolerance, to a septic dose (1 or 3 mg/kg) of the
      same LPS in male and female rats. We demonstrate significant differences,
      particularly in males, in the fever profiles of neonatally LPS-treated rats
      compared to neonatally saline-treated controls. Specifically, male rats treated
      neonatally with LPS have reduced hypothermic and enhanced hyperthermic responses
      to both septic doses of LPS in adulthood. A somewhat different profile is seen in
      females, with neonatally LPS-treated females having reduced hypothermia and
      enhanced hyperthermia compared to controls with 1 mg/kg but no differences with 3
      mg/kg LPS. The results obtained demonstrate that alterations in innate immune
      responses previously reported for low doses of LPS can, for the most part, also
      be observed after severe immune challenge in later life.

PMID- 20136691
TI  - A rapid interference between glucocorticoids and cAMP-activated signalling in
      hypothalamic neurones prevents binding of phosphorylated cAMP response element
      binding protein and glucocorticoid receptor at the CRE-Like and composite GRE
      sites of thyrotrophin-releasing hormone gene promoter.
AB  - Glucocorticoids or cAMP increase, within minutes, thyrotrophin-releasing hormone
      (TRH) transcription in hypothalamic primary cultures, although this effect is
      prevented if cells are simultaneously incubated with both drugs. Rat TRH promoter
      contains a CRE site at -101/-94 bp and a composite GRE element (cGRE) at -218/
      197 bp. Nuclear extracts of hypothalamic cells incubated with 8Br-cAMP or
      dexamethasone, and not their combination, bind to oligonucleotides containing the
      CRE or cGRE sequences. Adjacent to CRE are Sp/Kruppel response elements, and
      flanking the GRE half site, two AP1 binding sites. The present study aimed to
      identify the hypothalamic transcription factors that bind to these sites. We
      verified that the effects of glucocorticoid were not mimicked by corticosterone
      bovine serum albumin. Footprinting and chromatin immunoprecipitation (ChIP)
      assays were used to examine the interaction of cAMP- and glucocorticoid-mediated
      regulation of TRH transcription at the CRE and cGRE regions of the TRH promoter.
      Nuclear extracts from hypothalamic cells incubated for 1 h with cAMP or
      glucocorticoids protected CRE. The GRE half site was recognised by nuclear
      proteins from cells stimulated with glucocorticoids and, for the adjacent AP-1
      sites, by nuclear proteins from cells stimulated with cAMP or phorbol esters.
      Protection of CRE or cGRE was lost if cells were coincubated with dexamethasone
      and 8Br-cAMP. ChIP assays revealed phospho-CREB, c-Jun, Sp1, c-Fos and GR
      antibodies bound the TRH promoter of cells treated with cAMP or glucocorticoids;
      anti:RNA-polymerase II immunoprecipitated TRH promoter in a similar proportion as
      anti:pCREB or anti:GR. Recruitment of pCREB, SP1 or GR was lost when cells were
      exposed simultaneously to 8Br-cAMP and glucocorticoids. The data show that while
      pCREB and Sp1 bind to CRE-2, or GR to cGRE of the TRH promoter, the mutual
      antagonism between cAMP and glucocorticoid signalling, which prevent their
      binding to TRH promoter, could serve as a mechanism by which glucocorticoids
      rapidly suppress cAMP and noradrenaline-stimulated TRH transcription.

PMID- 20136692
TI  - Androgen decreases dopamine neurone survival in rat midbrain.
AB  - Clinical studies show that men are more likely to develop disorders affecting
      midbrain dopaminergic pathways, such as drug addiction and Parkinson's disease
      (PD). Although a great deal of focus has been given to the role of oestrogen in
      the maintenance of midbrain dopaminergic pathways, little is known about how
      testosterone influences these pathways. In the present study, we used
      stereological analysis of tyrosine hydroxylase-immunoreactive (TH-IR) cell bodies
      to determine how testosterone influences the dopaminergic cell bodies of the
      substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Rats and
      mice were castrated at postnatal day (PN) 60, and these midbrain cell populations
      were counted on PN 90. One month after castration, TH-IR cell number had
      increased in the SNpc and VTA of rats and mice. Replacement with testosterone or
      the non-aromatisable analogue dihydrotestosterone (DHT) in castrated animals
      reduced TH-IR cell number in the SNpc and VTA in rats. In mice, the decrease of
      TH-IR cell number with testosterone or DHT replacement was observed only in the
      SNpc. The apparent increase in TH-IR neurone number after castration is not
      explained by an increase in TH expression because the number of nondopaminergic
      cells (TH-immunonegative, TH-IN) did not decrease proportionally after
      castration. TH-IN cell number did not change after castration or hormone
      replacement in rat or mouse SNpc or VTA. These findings suggest that testosterone
      may play a suppressive role in midbrain dopaminergic pathways.

PMID- 20136693
TI  - Oestrogen receptors enhance dopamine neurone survival in rat midbrain.
AB  - Previous findings in our laboratory and elsewhere have shown that ovariectomy of
      rats in adulthood attenuates cocaine-stimulated locomotor behaviour. Ovarian
      hormones enhance both cocaine-stimulated behaviour and increase dopamine overflow
      after psychomotor stimulants. The present study aimed to determine whether
      ovarian hormones have these effects in part by maintaining dopamine neurone
      number in the substantia nigra pars compacta (SNpc) and ventral tegmental area
      (VTA) and to investigate the roles of specific oestrogen receptors (ERs) in the
      maintenance of mesencephalic dopamine neurones. To accomplish this goal, we used
      unbiased stereological techniques to estimate the number of tyrosine hydroxylase
      immunoreactive (TH-IR) cell bodies in midbrain regions of intact, ovariectomised
      and hormone-replaced female rats and mice. Animals received active or sham
      gonadectomy on postnatal day 60 and received vehicle, 17beta-oestradiol (E(2)) or
      selective ER agonists propyl-pyrazole-triol (PPT, ERalpha) or diarylpropionitrile
      (DPN, ERbeta) for 1 month post-surgery. In both rats and mice, ovariectomy
      reduced the number of TH-IR cells in the SNpc and VTA. Replacement with E(2), PPT
      or DPN prevented or attenuated the loss observed with ovariectomy in both rats
      and mice. An additional study using ER knockout mice revealed that adult female
      mice lacking ERalpha had fewer TH-IR cells in midbrain regions than wild-type
      mice, whereas mice lacking ERbeta had TH-IR cell counts comparable to wild-type.
      These findings suggest that, although both ER subtypes play a role in the
      maintenance of TH-IR cell number in the SNpc and VTA, ERalpha may play a more
      significant role.

PMID- 20136694
TI  - Developmental and steroidogenic effects on the gene expression of RFamide related
      peptides and their receptor in the rat brain and pituitary gland.
AB  - RFamide related peptides (RFRPs) have been extensively implicated in the
      neuroendocrine control of reproduction. While steroid hormones strongly regulate
      the closely-related kisspeptin gene and protein expression, the regulation of
      RFRPs or their receptor by steroid hormones is almost unknown. The present study
      aimed to quantify relative levels of RFRP and Kiss1 gene expression and their G
      protein-coupled receptors (GPR147 and GPR54, respectively) in various brain areas
      and the pituitary gland, and to determine the effects of differing levels of
      oestradiol and pubertal development on levels of these gene products. In
      Experiment 1, the treatment groups examined were: dioestrus, ovariectomised and
      ovariectomised with replacement oestradiol to induce a preovulatory-like
      luteinising hormone surge. Micropunched brain regions and whole pituitary glands
      were processed for measurement of RFRP, Kiss1, GPR147 and GPR54 mRNA by
      quantitative reverse transcriptase-polymerase chain reaction. As expected, Kiss1
      gene expression was low in the rostral periventricular area of the third
      ventricle of ovariectomised animals, whereas levels were highest in the arcuate
      nucleus in this situation. No such oestrogenic effects were observed for RFRP
      gene expression. GPR147 gene expression was highest in the rostral
      periventricular region of the third ventricle. The levels of GPR147 and GPR54
      mRNA were markedly lower in the pituitary gland than in the hypothalamic regions,
      and RFRP and Kiss1 mRNA were virtually undetectable in the pituitary gland. These
      data imply that the actions of RFamides are likely to be predominantly central in
      nature. In Experiment 2, hypothalamic RFRP and GPR147 mRNA levels were measured
      in male and female rats aged 2, 4, 6 and 8 weeks. In females, RFRP gene
      expression increased with developmental age, peaking around the time of puberty,
      whereas in males gene expression increased between 2 and 4 weeks of age. These
      results suggest a role in the regulation of adult reproduction rather that
      prepubertal infertility.

PMID- 20136695
TI  - Re: Xu N, Zhou W, Shuy L, Zhou G, Zhang N. Clinical and MRI characteristics of
      Levamisole-induced leukoencephalopathy in 16 patients. J Neuroimaging 2009;13:326
      331.

PMID- 20136696
TI  - Thalamic volume and dystonia in Machado-Joseph disease.
AB  - BACKGROUND AND PURPOSE: Neuropathological studies and one positron emission
      tomography study demonstrated involvement of the thalamus in Machado-Joseph
      disease (MJD), but a large series of patients has not been studied. Our objective
      was to perform an automated and a manual segmentation of the thalamus in patients
      with MJD. METHODS: We used the MarsBar volume of interest analysis toolbox to
      SPM2 and selected thalamic region of interests and we performed a t-test with
      Bonferroni's correction using SPM2 to compare patients to control. Next, we
      performed manual segmentation of the thalamus using the display software.
      Differences between patients and controls were analyzed by t-test. We also
      correlated manual thalamic volumes with clinical and genetic markers of the
      disease. RESULTS: We observed decreased thalamic volumes in MJD when compared to
      controls using both methods of volumetric measurement. MJD patients with dystonia
      had smaller volumes than patients without dystonia. CONCLUSIONS: We confirmed
      thalamic involvement in MJD patients. Patients with dystonia had smaller thalamic
      volumes than patients without dystonia. We observed a clinical-anatomical
      correlation, which suggests that different phenotypes of the disease present
      different primary or secondary targets of the disease.

PMID- 20136697
TI  - Paxillin expression levels are correlated with clinical stage and metastasis in
      salivary adenoid cystic carcinoma.
AB  - AIMS: To investigate the relationship between paxillin expression and
      clinicopathological features and metastasis in salivary adenoid cystic carcinoma
      (SACC). METHODS: A total of 47 SACC were assessed histochemically for paxillin
      expression. Paxillin immunoreactivity was compared with histological type,
      clinical stage and distant metastasis. RESULTS: Paxillin expression was
      identified in 57.45% of SACC as cytoplasmic staining and the expression was
      correlated with distant metastasis and clinical stage (P < 0.05), but not with
      histological type. CONCLUSIONS: Our observations indicate that paxillin
      expression is upregulated in SACC. High expression of paxillin was correlated
      with a more advanced stage and metastasis in SACC, suggesting that paxillin is a
      disease marker in advanced SACC and SACC with distant metastasis, and,
      consequently, may have value as a therapeutic target for SACC.

PMID- 20136698
TI  - Minichromosome maintenance-7 and geminin are reliable prognostic markers in
      patients with oral squamous cell carcinoma: immunohistochemical study.
AB  - BACKGROUND: Minichromosome maintenance (MCM) proteins act as the origin licensing
      machinery that regulates initiation of DNA replication. Geminin is a licensing
      repressor and prevents reinitiation of DNA replication by blocking reloading of
      MCM proteins at replication origins. Recent studies have proposed that MCM7 and
      geminin may be sensitive proliferative and prognostic markers of various
      malignant tumors. This study aimed to analyze the expression of MCM7 and geminin
      to clarify pathobiological significance in human oral squamous cell carcinomas
      (OSCCs). METHODS: We performed immunohistochemical analysis on 10 specimens of
      normal oral epithelia, 50 lesions with dysplasia and 113 OSCCs. Labeling indices
      (LIs) for MCM7, geminin and Ki-67 were evaluated, comparing with
      clinicopathological profiles. RESULTS: The mean LIs for MCM7 were 29.2% for
      normal epithelia, 32.2% for dysplasias, and 51.1% for OSCCs; the value was
      significantly higher in the last than in the former two (P < 0.01). The mean LIs
      for geminin were 6.8% for normal epithelia, 9.2% for dysplasias, and 21.3% for
      OSCCs; the value was significantly higher in the OSCCs (P < 0.01). The MCM7 LIs
      were correlated with the histological grade of OSCCs, in which the highest LIs
      were noted in the poorly differentiated type (P < 0.01). The survival rate was
      significantly lower in patients with a higher MCM7 LI (>49.5%) than in those with
      a lower LI (P < 0.05) at stage III-IV. However, the survival rate in the patients
      with a higher geminin LI (>19.5%) was significantly higher than in those with a
      lower LI (P < 0.05) at stage IV.

PMID- 20136699
TI  - Development of a ceramic primer with higher bond durability for resin cement.
AB  - To increase the bond durability of resin to the CAD/CAM ceramic surface, two
      types of two-bottle type ceramic primers, consisting of Primer A1 or A2 and
      Primer B, were designed. Primer A1 was prepared by dissolving 25, 50, or 100 mg
      of gamma-methacryloxypropyltrimethoxysilane in 1 mL of ethanol. Primer A2 was
      prepared by dissolving 50 mg of mixed silanes, consisting of 1,2
      bis(trimethoxysilyl)ethane to gamma-methacryloxypropyltrimethoxysilane, in 1 mL
      of ethanol. Mole fractions of 1,2-bis(trimethoxysilyl)ethane to gamma
      methacryloxypropyltrimethoxysilane were 0, 10, 20, 30, 40 and 50 mol%. Primer B
      was prepared after dissolving 0.01, 0.05 or 0.1 mol L(-1) hydrochloric acid in
      ethanol by 50 vol%. Ceramic surface was silanated with a mixture of Primers A1
      and B or Primers A2 and B for 1 min, and then air-dried. Commercial GC ceramic
      primer and Porcelain Liner M were utilized. Thereafter, dual-curing type resin
      cement was bonded to silanated ceramic surface through visible-light irradiation.
      Shear bond strength of resin to the ceramic surface was measured, before and
      after thermo-cycling. Addition of 0.01 or 0.05 mol L(-1) hydrochloric acid to the
      gamma-methacryloxypropyltrimethoxysilane allowed for significant increases in the
      bond strength. However, thermo-cycling resulted in significant decreases of
      approximately 5 MPa in the bond strength. Conversely, when the mixed silane,
      where 30 mol% of 1,2-bis(trimethoxysilyl)ethane dissolved in gamma
      methacryloxypropyltrimethoxysilane, was utilized with 0.05 mol L(-1) hydrochloric
      acid, the reduction in the bond strength decreased to approximately 2 MPa. The
      designed ceramic primers exhibited higher ceramic bond durability than commercial
      ceramic primers.

PMID- 20136700
TI  - Types and timing of breastfeeding support and its impact on mothers' behaviours.
AB  - AIM: To determine the types and timing of breastfeeding support for mothers of
      newborn babies and the extent to which this affects breastfeeding intentions and
      behaviours in a region with low rates of breastfeeding initiation and duration.
      METHODS: A cross-sectional study by interviewer-administrated questionnaire was
      undertaken of women birthing at a large teaching hospital in South Western
      Sydney, between August and October 2006 (n= 164), with a 2-week follow-up of
      breastfeeding or breastfeeding-intending women (n= 107). Types, timing and
      satisfaction with personal and professional sources of support (e.g. antenatal
      classes, help at birth, practical lessons on how to breastfeed, providing
      information, and attitude towards breastfeeding) and the impact of these on
      breastfeeding intention and behaviours were assessed. RESULTS: Most women had
      intended to breastfeed (76.2%), and, within the first 24 hours, 77.4% of babies
      were breastfed to some extent (45.1% exclusively), and at 2 weeks 65.9% were
      breastfed (9.7% exclusively). Women felt most supported by their partners and
      least supported by their health-care team. Antenatal classes, breastfeeding help
      within half an hour of birth and positive health-care team attitudes were related
      to improved breastfeeding intentions and behaviours. However, these supports were
      infrequently reported. Personal support was commonly reported although support
      delivered by professionals was related to better breastfeeding behaviours.
      CONCLUSION: Despite the effectiveness of professional support interventions,
      particularly those delivered in the antenatal and immediate post-natal period,
      access to these sources of support was very low. For breastfeeding outcomes to be
      improved, effective professional support strategies need to be much more widely
      available.

PMID- 20136701
TI  - Amyloid-beta neurotoxicity in organotypic culture is attenuated by melatonin:
      involvement of GSK-3beta, tau and neuroinflammation.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by
      accumulation of extracellular deposits of amyloid-beta (Abeta) peptide in brain
      regions that are important for memory and cognition. The buildup of Abeta
      aggregates in the AD is followed by the formation of intracellular
      neurofibrillary tangles and activation of neuroinflammatory reactions. The
      present study investigated whether melatonin possesses a neuroprotective effect
      against Abeta-induced toxicity. For this purpose, organotypic hippocampal slices
      were cultured and exposed to 25 microm of Abeta(25-35) in the absence or in the
      presence of melatonin (25, 50, or 100 microm). In addition, the authors have
      investigated the involvement of GSK-3beta, tau protein, astroglial, and
      microglial activation, and cytokine levels in the melatonin protection against
      Abeta-induced neurotoxicity. Melatonin prevented the cell damage in hippocampus
      induced by the exposure to Abeta(25-35). In addition, melatonin significantly
      reduced the activation of GSK-3beta, the phosphorylation of tau protein, the
      glial activation and the Abeta-induced increase of TNF-alpha and IL-6 levels. On
      the basis of these findings, we speculate that melatonin may provide an effective
      therapeutic strategy for AD, by attenuating Abeta-induced phosphorylation of tau
      protein, and preventing GSK-3beta activation and neuroinflammation.

PMID- 20136702
TI  - Melatonin suppresses cyclosporine A-induced autophagy in rat pituitary GH3 cells.
AB  - Cyclosporine A (CsA) is a powerful immunosuppressive drug with side effects
      including the induction of chronic nephrotoxicity including endoplasmic reticulum
      (ER) stress in tubular cells. Recently, it was reported that autophagy is induced
      by ER stress and serves to alleviate the associated deleterious effects. In the
      current study, CsA treatment (0-100 microm) decreased cell survival of rat
      pituitary GH3 cells in a dose-dependent manner. At concentrations ranging from
      1.0 to 10 microm, CsA induced a dose-dependent increase in the expression of
      microtubule-associated protein 1 light chain 3 (LC3)-I and LC3-II. Cells treated
      with 2.5 microm CsA exhibited cytoplasmic vacuolation, indicating that CsA
      induces autophagy in rat pituitary GH3 cells. In the presence of 1.0-10 microm
      CsA, the expression of catalase decreased while that of the ER stress markers, ER
      luminal binding protein (BiP) and inositol-requiring enzyme 1 alpha (IRE1alpha),
      increased as compared those levels in untreated cells. These results suggested
      that CsA-induced autophagy is dependent on ER stress. To determine whether
      melatonin would protect cells against CsA-induced autophagy, we treated rat
      pituitary GH3 cells with melatonin in the presence of CsA. Melatonin treatment
      (100 and 200 microm) suppressed autophagy induced by 2.5 and 5 microm CsA.
      Furthermore, co-treatment with 100 microm melatonin inhibited LC3-II expression,
      and increased catalase and phosphorylated p-ERK levels in the presence of 2.5 and
      5 microm CsA. BiP and IRE1alpha expression in melatonin-co-treated cells was
      superior to that in cells treated with 2.5 and 5 microm CsA alone. Thus,
      melatonin suppresses CsA-mediated autophagy in rat pituitary GH3 cells.

PMID- 20136703
TI  - Melatonin protects periventricular white matter from damage due to hypoxia.
AB  - This study investigated the potential of melatonin in ameliorating hypoxic damage
      to the periventricular white matter (PWM) in the neonatal brain. Vascular
      endothelial growth factor (VEGF), nitric oxide (NO), glutathione (GSH) and
      malondialdehyde (MDA) content in the PWM of 1-day-old rats subjected to hypoxia
      for a period of 2 hr was examined. Vascular endothelial growth factor, NO and MDA
      concentration was increased whereas that of GSH was reduced after the hypoxic
      exposure. Additionally, degenerating axons, apoptotic and necrotic cells and
      vacuolation of capillary endothelial cells were observed in the PWM. The
      neighboring ependymal and choroid plexus cells also appeared to undergo
      structural alterations. Increased vascular permeability in the PWM of hypoxic
      rats was evidenced by the leakage of rhodamine isothiocyanate (RhIC) which was
      taken up by the amoeboid microglial cells. In vitro experiments showed increased
      apoptosis in OLN-93 cells, an oligodendrocytic cell line, following hypoxic
      exposure. Hypoxic rats treated with melatonin showed reduced VEGF, NO and MDA
      concentrations, increased GSH content and reduced RhIC leakage in the PWM. The
      ultrastructure of axons, endothelial, ependymal and choroid plexus epithelial
      cells appeared relatively normal in the hypoxic animals treated with melatonin.
      The incidence of apoptotic OLN-93 cells was also reduced with melatonin
      treatment. We suggest that the protective effects of melatonin on various
      parameters in the PWM of hypoxic neonatal brains were due to its antioxidant
      properties.

PMID- 20136704
TI  - Porcelain fracture resistance of screw-retained, cement-retained, and screw
      cement-retained implant-supported metal ceramic posterior crowns.
AB  - PURPOSE: The purpose of this in vitro study was to compare the porcelain fracture
      resistance between screw-retained, cement-retained, and combined screw- and
      cement-retained metal-ceramic (MC) implant-supported posterior single crowns; and
      to investigate the effect of offsetting the occlusal screw-access opening on
      porcelain fracture resistance of screw-retained and cement-retained MC implant
      supported posterior single crowns. MATERIALS AND METHODS: Forty standardized MC
      molar-shaped restorations were fabricated. The 40 restorations were divided into
      four groups (SRC, SRO, CRP, and CSC) of 10 specimens each. Group SRC: screw
      retained, screw-access hole placed in the center of the occlusal surface; Group
      SRO: screw-retained, screw access hole placed 1 mm offset from the center of the
      occlusal surface toward the buccal cusp; Group CRP: cement-retained, zinc
      phosphate cement was used; Group CSC: cement-retained with a screw-access hole in
      the center of the occlusal surface. The screw-retained restorations and abutments
      were directly attached to 3i implant fixtures embedded in acrylic resin blocks.
      Subsequently, all test specimens were thermocycled and vertically loaded in a
      universal testing machine at a crosshead speed of 2 mm/min until fracture. Mean
      values of load at fracture (in N) were calculated in each group and compared with
      a one-way ANOVA and Tukey's Studentized test (alpha= 0.05). RESULTS: Mean values
      of loads required to fracture the restorations were as follows (N): Group SRC:
      1721 +/- 593; Group SRO: 1885 +/- 491; Group CRP: 3707 +/- 1086; Group CSC: 1700
      +/- 526. Groups SRC, SRO, and CSC required a significantly lower force to
      fracture the porcelain than did the CRP group (p < 0.05). CONCLUSION: The cement
      retained restorations showed significantly higher mean fracture loads than the
      restorations having screw-access openings in their occlusal surface. The position
      of the screw-access hole within the occlusal surface did not significantly affect
      the porcelain fracture resistance.

PMID- 20136705
TI  - Sexual function and quality of life in women with urinary incontinence treated by
      a complete pelvic floor rehabilitation program (biofeedback, functional
      electrical stimulation, pelvic floor muscles exercises, and vaginal cones).
AB  - INTRODUCTION: Urinary incontinence (UI) is a debilitating condition that can
      cause discomfort, embarrassment, loss of confidence; it can lead to withdrawal
      from social life, and adversely affects physical and mental health, sexual
      function and quality of life (QoL) in women. AIM: The aim is to determine the
      impact of combined pelvic floor rehabilitation (PFR) on UI, female sexual
      dysfunction, and QoL. MAIN OUTCOME MEASURES: Female Sexual Function Index
      questionnaire (FSFI) and King's Health Questionnaire (KHQ). METHODS: Sixteen
      patients with UI were selected and underwent a complete PFR program (biofeedback,
      functional electrical stimulation, pelvic floor muscles exercises, and vaginal
      cones). Patient filled out the FSFI questionnaire and the KHQ at the baseline and
      at follow-up. RESULTS: After PFR none of the patients reported urine leakage
      during sexual activity. Resolution of incontinence was achieved in 13 (81.25%)
      women. Only three (18.75%) patients had positive 1-hour pad test after the
      treatment. There was significant difference between pad test leakage before and
      after the PFR (P < 0.001). The mean Stamey incontinence score was 1.37 +/- 0.5 at
      the baseline vs. 0.25 +/- 0.57 at the follow up (P < 0.001). Before PFR, FSFI
      total score ranged from 25.8 to 2 (mean 14.65 +/- 6.88), after treatment the FSFI
      total score ranged from 36 to 2 (mean 22.65 +/- 9.5) (P < 0.001). The improvement
      of the scores in the six FSFI domains, 5 months after the conclusion of PFR, was
      statistically significant (desire, arousal, lubrication, orgasm, satisfaction,
      and pain). All the nine domains in the KHQ presented a low average score after
      treatment and the improvements were statistically significant. CONCLUSIONS: PFR
      led to a significant difference in the daily use of pads, 1-hour pad test, and
      Stamey incontinence scores. The treatment caused an improvement in patient's QoL
      index and sexual function.

PMID- 20136706
TI  - Neuronal activity in the hypothalamic paraventricular nucleus varies across the
      estrous cycle in anesthetized female rats: effects of dopamine receptor agonism.
AB  - PURPOSE: The central nervous system plays a pivotal role in sexual behavior. The
      role of the paraventricular nucleus (PVN) of the hypothalamus in female sexual
      behavior is poorly characterized. In males, there is a correlation between PVN
      neuron activity and erectile activity, and in mediating dopamine receptor agonist
      induced sexual arousal. MATERIAL AND METHODS: To understand the role of the PVN
      in female sexual function, baseline PVN neuronal activity and responses to
      dopamine receptor agonism were assessed in anesthetized rats. Single unit
      recordings were used to assess the firing properties of individual PVN neurons;
      and local field potentials quantified PVN network activity (combined activity of
      large numbers of PVN neurons). Baseline and apomorphine-stimulated activity was
      measured across the estrous cycle. RESULTS: Baseline firing rates of single units
      were found to differ across the stages of the estrous cycle with metestrus
      showing the highest firing rate (3.7 vs. 0.9 Hz in diestrus). Apomorphine
      administration caused significant increases in firing rate in 29% of neurons, and
      significant decreases in 71%. Basal local field potentials also varied between
      estrous stages and in response to apomorphine; significant differences in the
      total power of alpha1 and beta1 bands were observed in both cases. CONCLUSIONS:
      This study shows that PVN neuronal activity varies with hormonal state, and these
      neurons are differentially affected by apomorphine, suggesting two different
      populations. These data are indicative of a critical role for the PVN in female
      sexual function. It is important that the hormonal state should be considered
      when investigating sexual physiology and the effect of pharmacological agents.

PMID- 20136707
TI  - Characteristics, behaviors, and attitudes of men bypassing the healthcare system
      when obtaining phosphodiesterase type 5 inhibitors.
AB  - INTRODUCTION: Men may choose to bypass the healthcare system to obtain a
      phosphodiesterase type 5 inhibitor (PDE5i). AIM: Evaluate the characteristics and
      purchasing patterns of men obtaining a PDE5i without prior healthcare
      professional (HCP) interaction. MAIN OUTCOME MEASURES: Prior HCP interaction,
      defined as having a prescription for any PDE5i, having a PDE5i sample from a
      physician, or buying the PDE5i in a retail pharmacy; and erectile dysfunction
      (ED, the Massachusetts Male Aging Study single-item question) were assessed. A
      multivariate regression analysis determined predictive factors for PDE5i purchase
      without prior HCP interaction. Methods. A Web-based observational study was
      conducted in the United Kingdom, Germany, and Italy. RESULTS: Of the 11,899
      participants, 1,252 (10.5% [95% CI, 10.0-11.1%]) reported PDE5i use in the last 6
      months. PDE5is were obtained without prior HCP interaction by 403 users (32.3%
      [95% CI, 29.6-34.8%]); 65.5% of them had ED. Overall prevalence of men using
      PDE5is without HCP interaction was 3.0% (95% CI, 2.6-3.5%), 4.1% (95% CI, 3.5
      4.6%), and 2.8% (95% CI, 2.1-3.5%) for men aged 18-34, 35-50, and >50 years,
      respectively (P = 0.0045). Predictive factors for obtaining a PDE5i without prior
      HCP interaction were embarrassment to speak to a physician (P = 0.0009) and the
      perception that this would be the cheapest way to get the medicine (P = 0.03).
      CONCLUSIONS: Based on these findings, it can be estimated that approximately 6
      million men in Europe might currently bypass the healthcare system to obtain a
      PDE5i. In addition to the risks associated with use of PDE5is from uncontrolled
      sources, because most of these men have ED, they also miss the opportunity for
      important health information or medical follow-up. HCPs should actively address
      ED and offer treatment to discourage men from seeking uncontrolled sources of ED
      medicines.

PMID- 20136708
TI  - Plasma Chitotriosidase Activity and Arteriogenic Erectile Dysfunction:
      Association with the Presence, Severity, and Duration.
AB  - Introduction. Plasma chitotriosidase (ChT) activity is associated with the
      presence of atherosclerosis and is a new cardiovascular risk marker. Although
      available evidence supports its role in atherogenesis, there is a lack of an
      obvious correlation between plasma ChT activity and erectile dysfunction (ED).
      Aim. Our aim was to investigate the association of the level of serum ChT
      activity with ED. Main Outcome Measures. Erectile function was assessed using
      Sexual Health Inventory for Men (SHIM). Serum fasting lipid profile (plasma total
      cholesterol, low density lipoprotein cholesterol, high density lipoprotein
      cholesterol, and triglycerides); sex hormones (luteinizing hormone, follicle
      stimulating hormone, prolactin, total testosterone, and estradiol); and thyroid
      stimulating hormone were measured. Plasma ChT activity, as well as K(m), V(max),
      optimum pH, and heat stability of the ChT were also assessed. Penile duplex
      ultrasound examination before and after intracavernous injection of 20 microg
      prostaglandin E1 (PGE(1)), pudendal nerve conduction tests and sensory-evoked
      potential studies were done to identify patients with arteriogenic ED. Intima
      media thickness (IMT) and plaque formation of common carotid artery were
      determined bilaterally using B-mode ultrasonography. Methods. A total of 124
      normolipidemic patients with ED and 120 healthy controls were recruited for this
      study. Results. Serum ChT activity in patients with ED (116 +/- 18 nmol/h/mL) was
      significantly higher than in normal control subjects (51 +/- 12 nmol/h/mL) (P <
      0.001). There was a significant positive correlation between plasma ChT activity
      and (i) severity of ED and (ii) duration of ED (r = 0.68, P = 0.004; and r =
      0.62, P = 0.01 respectively).We also found that all ChT kinetic parameters
      assessed (K(m), V(max), and optimum pH) in plasma of ED patients were
      significantly different from those of normal controls (all P < 0.001). The
      results of heat stability analysis, demonstrated that plasma ChT activity in the
      normal individuals was more stable than in the patients with arteriogenic ED (P <
      0.001). A significant correlation was seen between the plasma ChT activity and
      the mean common carotid IMT (r = 0.78, P = 0.002). Moreover, a significant
      correlation was seen between the severity of ED and mean common carotid IMT (r =
      0.74, P = 0.003). We did not address chitotriosidase genotype. Conclusions. Our
      results indicate that plasma ChT activity is increased in normolipidemic patients
      with arteriogenic ED, suggesting its possible role in the pathophysiology of
      arteriogenic ED. The clinical significance of this increase should be assessed in
      further studies. Safarinejad MR, and Safarinejad SH. Plasma chitotriosidase
      activity and arteriogenic erectile dysfunction: Association with the presence,
      severity, and duration. J Sex Med **;**:**-**.

PMID- 20136709
TI  - Induction of sexual arousal in women under conditions of institutional and
      ambulatory laboratory circumstances: a comparative study.
AB  - INTRODUCTION: Measuring under naturally occurring circumstances increases
      ecological validity. We developed an ambulatory psychophysiological laboratory
      that allows experiments to be performed at home. AIMS: To compare institutional
      laboratory task measures with ambulatory laboratory task measures. MAIN OUTCOME
      MEASURES: Vaginal pulse amplitude (VPA), clitoral blood volume (CBV), subjective
      report of sexual arousal, preconscious attentional bias for erotic stimuli,
      subjective reports about feeling at ease, tense, anxious or inhibited. METHODS:
      VPA and CBV were measured in eight women with hypoactive sexual desire disorder
      (HSDD) and eight healthy controls while exposed to neutral and erotic film clips
      both in the institute's laboratory and at home. Before and after film clip
      presentations, subjects performed an emotional Stroop task and completed two
      questionnaires. RESULTS: In healthy controls, genital measures of sexual arousal
      were significantly increased at home compared with the institutional laboratory,
      whereas no differences were observed between the institutional laboratory and the
      at home measurements in women with HSDD. The responses at home were significantly
      higher in healthy controls compared with women with HSDD. Subjective experience
      of genital responding increased at home for both groups of women. Concordance
      between subjective experience and genital sexual arousal was more pronounced in
      the institutional laboratory setting. Preconscious attentional bias was stronger
      in the institutional laboratory for both groups of women. Healthy controls felt
      more at ease and less inhibited at home while subjects with HSDD did not.
      CONCLUSIONS: The use of an ambulatory laboratory is a valuable tool allowing
      psychophysiological (sex) research under more natural circumstances (e.g., a
      participant's home). In this study, the increase in ecological validity resulted
      in a qualitative differentiation between the healthy controls and the women with
      HSDD in the home setting, which is not apparent in the artificial setting of the
      institutional laboratory.

PMID- 20136710
TI  - Quantitation of bleeding symptoms in children with von Willebrand disease: use of
      a standardized pediatric bleeding questionnaire.
AB  - SUMMARY BACKGROUND: Excessive bruising and mucocutaneous bleeding are frequent
      presenting symptoms in childhood. A detailed bleeding history can distinguish
      children who may have an inherited bleeding disorder from those who are normal.
      There is a lack of standardization of such history taking in pediatric practise.
      OBJECTIVES: To assess the performance of a Pediatric Bleeding Questionnaire
      (PBQ), an adaptation of a standardized adult bleeding questionnaire and score
      that includes pediatric-specific bleeding symptoms, in a cohort of children with
      von Willebrand disease (VWD). PATIENTS/METHODS: Bleeding scores were determined
      by interview, for children with a previous diagnosis of VWD and a control group
      of unaffected siblings. RESULTS: Bleeding scores were obtained for 100 children
      with VWD, median age 10.9 years (range, 0.8-17.8 years), and 21 unaffected
      siblings. Median bleeding score in children with VWD was 7.0 (range, 0-29) and in
      the control group was 0 (range, -1-2). Bleeding score varied within and between
      each VWD type: definite type 1, n = 40, median, 9.0 (range, 2-18); possible type
      1, n = 38, median, 2.0 (0-15); type 2, n = 6, median, 14.0 (3-17); and type 3, n
      = 16, median, 12.0 (4-29). Bleeding scores in affected children correlated with
      age (Spearman's correlation coefficient, 0.35; P = 0.0004). The most frequent
      clinically significant bleeding symptoms were surgical bleeding, bleeding after
      tooth extraction and menorrhagia. Post-circumcision bleeding, cephalohematoma,
      macroscopic hematuria and umbilical stump bleeding were clinically significant in
      32% (of circumcised males), 4%, 4% and 3% of children, respectively. CONCLUSIONS:
      The PBQ provides a standardized quantitation of bleeding severity in children
      with VWD.

PMID- 20136711
TI  - Ability of a 5-minute electrocardiography (ECG) for predicting arrhythmias in
      Doberman Pinschers with cardiomyopathy in comparison with a 24-hour ambulatory
      ECG.
AB  - BACKGROUND: Ventricular premature contractions (VPCs) are common in the occult
      stage of cardiomyopathy in Doberman Pinschers. Although the gold standard for
      detecting arrhythmia is the 24-hour ambulatory electrocardiography (ECG)
      (Holter), this method is more expensive, time-consuming and often not as readily
      available as common ECG. OBJECTIVES: Comparison of 5-minute ECGs with Holter
      examinations. ANIMALS: Eight hundred and seventy-five 5-minute ECGs and Holter
      examinations of 431 Doberman Pinschers. METHODS: Each examination included a 5
      minute ECG and Holter examination. A cut-off value of > 100 VPCs/24 hours using
      Holter was considered diagnostic for the presence of cardiomyopathy. Statistical
      evaluation included calculation of sensitivity, specificity, positive predictive
      value, and negative predictive value. RESULTS: Holter examinations revealed > 100
      VPCs/24 hours in 204/875 examinations. At least 1 VPC during a 5-minute ECG was
      detected in 131 (64.2%) of these 204 examinations. No VPCs were found in the 5
      minute ECG in 73 (35.8%) examinations of affected Doberman Pinschers. A 5-minute
      ECG with at least 1 VPC as cut-off had a sensitivity of 64.2%, a specificity of
      96.7%, a positive predictive value of 85.6% and a negative predictive value of
      89.9% for the presence of > 100 VPCs/24 hours. CONCLUSIONS AND CLINICAL
      IMPORTANCE: A 5-minute ECG is a rather insensitive method for detecting
      arrhythmias in Doberman Pinschers. However, the occurrence of at least 1 VPC in 5
      minutes strongly warrants further examination of the dog, because specificity
      (96.7%) and positive predictive value (85.6%) are high and could suggest occult
      cardiomyopathy.

PMID- 20136712
TI  - Antibodies against Crandell Rees feline kidney (CRFK) cell line antigens, alpha
      enolase, and annexin A2 in vaccinated and CRFK hyperinoculated cats.
AB  - BACKGROUND: Cats inoculated with feline herpesvirus 1, calicivirus, and
      panleukopenia (FVRCP) vaccines grown on the Crandell Rees feline kidney (CRFK)
      cell line have been shown to develop anti-CRFK antibodies. The identities of
      common CRFK antigens are unknown. HYPOTHESIS: Cats inoculated with CRFK lysates
      and FVRCP vaccines will develop autoantibodies measurable by Western blot
      immunoassay. Antigens associated with these antibodies can be isolated for
      further study. ANIMALS: One CRFK hyperinoculated rabbit, 44 age-matched
      unvaccinated kittens purchased from a commercial vendor. METHODS: Commonly
      recognized CRFK antigens were identified by comparison of Western blot
      immunoassays using sera from a hyperinoculated rabbit and kittens inoculated with
      CRFK lysate or 1 of 4 commercially available FVRCP vaccines. Antigens were
      purified from CRFK lysates and sequenced. Antigen recognition was confirmed by
      Western blot immunoassay and indirect ELISA for 2 proteins using sera from CRFK
      and FVRCP inoculated kittens. RESULTS: CRFK antigens 47, 40, and 38 kD in size
      were identified. Protein isolation and sequencing identified 3 CRFK proteins as
      alpha-enolase, annexin A2, and macrophage capping protein (MCP). Sera from FVRCP
      and CRFK inoculated cats were confirmed to recognize annexin A2 and alpha-enolase
      by Western blot immunoassay and indirect ELISA. CONCLUSIONS AND CLINICAL
      RELEVANCE: This study validated the use of Western blot immunoassay for detection
      of antibodies against CRFK proteins and identified 3 CRFK antigens. In humans,
      alpha-enolase antibodies are nephritogenic; alpha-enolase and annexin A2
      antibodies have been associated with autoimmune diseases. Further research will
      be necessary to determine the clinical relevance of these findings.

PMID- 20136713
TI  - Comparison of 4 Giardia diagnostic tests in diagnosis of naturally acquired
      canine chronic subclinical giardiasis.
AB  - BACKGROUND: The performance of Giardia diagnostic tests that detect either cysts
      or fecal antigens has not been thoroughly examined. HYPOTHESIS/OBJECTIVES: We
      examined the concordance and agreement among 4 Giardia diagnostic tests (2 cyst
      and 2 coproantigen detection methods) in a colony of dogs chronically and
      subclinically infected with Giardia. ANIMALS: Twenty dogs with chronic,
      subclinical Giardia infection. METHODS: Giardia diagnostic tests were performed
      repeatedly on each dog over 120 days. Fecal cyst detection methods (ZnSO4
      flotation and fluorescent antibody [FAB] coproscopy) were performed 3 times per
      week. Coproantigen methods (Giardia SNAP test and quantitative ELISA) were
      performed weekly. Results were analyzed and compared among methods. RESULTS: When
      compared with FAB coproscopy, all of the in-house diagnostic tests had excellent
      positive predictive values (PPVs, 95-99%) at the study prevalence (89%). At lower
      prevalence rates, ZnSO4, SNAP, and ELISA tests all had good negative predictive
      values (NPVs), but poor PPVs. There was poor to good agreement among tests by
      kappa analysis. CONCLUSION AND CLINICAL RELEVANCE: Our findings show that most
      commonly used in-house Giardia diagnostic tests have poor agreement with the gold
      standard method (FAB coproscopy). The in-house tests have good NPVs, but poor
      PPVs, at prevalence rates common in most clinical settings.

PMID- 20136714
TI  - Progressive juvenile glomerulonephropathy in 16 related French Mastiff (Bordeaux)
      dogs.
AB  - BACKGROUND: Familial juvenile glomerulonephropathy (JGN) is reported in several
      breeds of dogs. The mode of inheritance and spectrum of pathological lesions vary
      among breeds. A progressive JGN was detected in a pedigree of French Mastiff (FM)
      dogs. OBJECTIVES: To describe clinical, laboratory, and histopathologic findings
      in related FM dogs suffering from progressive JGN and to determine the mode of
      inheritance of this condition. ANIMALS: Sixteen affected and 35 healthy related
      FM dogs METHODS: FM dogs < 24 months of age and diagnosed with chronic kidney
      disease with evidence of proteinuria entered the study. Clinical, laboratory,
      histopathologic findings, and pedigree data were recorded. RESULTS: Clinical
      signs were typical of progressive glomerulopathy with resultant renal failure.
      Increased blood urea nitrogen, creatinine and total cholesterol concentrations,
      and proteinuria were found in all patients. Affected dogs had abnormal kidney
      structure on abdominal ultrasound examination. Histopathologic examination
      revealed extensive cystic glomerular atrophy, glomerular hypercellularity, and
      capillary wall thickening without immune complex deposition when tested with
      immunohistochemistry or immunofluorescence. Electron microscopy did not disclose
      specific primary glomerular lesions. Mean age at death was 20 months and mean
      length of survival after diagnosis was 6 months. Both males and females from
      healthy parents were affected. An autosomal recessive mode of transmission is
      suspected, but a more complex mode of inheritance cannot be excluded. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Progressive familial JGN occurs in FM dogs.
      Characterization of the pathogenesis and mode of inheritance of this disease
      warrants additional study.

PMID- 20136715
TI  - Physiology and treatment of retained fetal membranes in cattle.
AB  - Retained fetal membranes (RFM) in cattle have adverse effects on fertility and
      production. Understanding the pathophysiology and causes of RFM is important for
      managing this disease. The hormonal processes that lead to normal placental
      separation are multifactorial and begin before parturition. A variety of risk
      factors, including early or induced parturition, dystocia, hormonal imbalances,
      and immunosuppression, can interrupt these normal processes and result in
      retention of the placenta. Current research does not support the efficacy of many
      commonly practiced treatments for RFM. Systemic administration of antibiotics can
      be beneficial for treating metritis after RFM, but antibiotic administration has
      not been shown to significantly improve future reproduction in cows with RFM.
      Collagenase injected into the umbilical arteries of retained placentas
      specifically targets the lack of placentome proteolysis and might enhance
      placental release. However, such therapy is costly and its benefits in terms of
      improving subsequent reproductive function have not been evaluated.

PMID- 20136716
TI  - Successful treatment of Rhodococcus equi pneumonia in an adult horse.

PMID- 20136717
TI  - Drug-induced minimal change nephropathy in a dog.

PMID- 20136718
TI  - Lactoferrin protects against concanavalin A-induced liver injury in mice.
AB  - BACKGROUND: Liver diseases, caused by viral infection, autoimmune conditions,
      alcohol ingestion or the use of certain drugs, are a significant health issue, as
      many can develop into liver failure. Lactoferrin (Lac) is an iron-binding
      glycoprotein that belongs to the transferrin family. Owing to its multiple
      biological functions, Lac has been evaluated in a number of clinical trials to
      treat infections, inflammation and cancer. AIM: The present study aims to reveal
      a profound hepatoprotective effect of Lac, using a mouse model of Concanavalin A
      (Con A)-induced hepatitis, which mimics the pathophysiology of human viral and
      autoimmune hepatitis. METHOD: C57Bl/6J mice were injected with bovine Lac
      following Con A challenge. The effects of Lac on interferon (IFN)-gamma and
      interleukin (IL)-4 expression were determined. The roles of Lac on T-cell
      apoptosis and activation, and leukocytes infiltration were examined. RESULT: The
      data demonstrated that the protective effect of Lac was attributed to its ability
      to inhibit T-cell activation and production of IFN-gamma, as well as to suppress
      IL-4 production by hepatic natural killer T cells. CONCLUSION: These findings
      indicate a great therapeutic potential of Lac in treating in treating
      inflammatory hepatitis and possibly other inflammatory diseases.

PMID- 20136719
TI  - Production of biological soil crusts in the early stage of primary succession on
      a high Arctic glacier foreland.
AB  - *We examined the photosynthetic characteristics and net primary production of
      biological soil crusts to evaluate their contribution to the carbon cycle in the
      High Arctic glacier foreland. *Biological soil crust samples were collected from
      a deglaciated area in Ny-Alesund, Svalbard, Norway. Net photosynthetic rates (Pn)
      and dark respiration rates (R) of biological soil crusts were determined using
      CO(2) gas exchange rates. We examined the effects of moisture conditions,
      temperature and photon flux density on Pn and R, and estimated the net primary
      production by a model based on the relationships between abiotic factors and Pn
      and R. *The maximum Pn value occurred at 50% of the maximum water-holding
      capacity. Pn decreased with increasing temperature and dropped below zero at high
      temperatures (c. > 13 degrees C). The estimated net primary production of the
      biological soil crust was greater than the net primary production of other
      vegetation when based on ground surface area, during the early stage of primary
      succession. Model simulation showed that the net primary production of the
      biological soil crust decreased with increasing temperature. *These results
      suggest that biological soil crust productivity plays an important role in the
      carbon cycle during the early stage of succession of the High Arctic glacier
      foreland, and is susceptible to temperature increases from global warming.

PMID- 20136720
TI  - Silica uptake in aquatic and wetland macrophytes: a strategic choice between
      silica, lignin and cellulose?
AB  - *Although silica (Si) is not an essential element for plant growth in the
      classical sense, evidence points towards its functionality for a better
      resistance against (a)biotic stress. Recently, it was shown that wetland
      vegetation has a considerable impact on silica biogeochemistry. However, detailed
      information on Si uptake in aquatic macrophytes is lacking. *We investigated the
      biogenic silica (BSi), cellulose and lignin content of 16 aquatic/wetland species
      along the Biebrza river (Poland) in June 2006 and 2007. The BSi data were
      correlated with cellulose and lignin concentrations. *Our results show that
      macrophytes contain significant amounts of BSi: between 2 and 28 mg BSi g(-1).
      This is in the same order of magnitude as wetland species (especially grasses).
      Significant antagonistic correlations were found between lignin, cellulose and
      BSi content. Interestingly, observed patterns were opposite for wetland
      macrophytes and true aquatic macrophytes. *We conclude that macrophytes have an
      overlooked but potentially vast storage capacity for Si. Study of their role as
      temporal silica sinks along the land-ocean continuum is needed. This will further
      understanding of the role of ecosystems on land ocean transport of this essential
      nutrient.

PMID- 20136721
TI  - Association of development of chronic lung disease of newborns with neonatal
      colonization of Ureaplasma and cord blood interleukin-8 level.
AB  - BACKGROUND: The aim of the present study was to investigate the association of
      chronic lung disease (CLD), neonatal Ureaplasma colonization, and interleukin-8
      (IL-8) level of cord blood in preterm infants. METHODS: In 77 infants of <32
      weeks gestation, the relationship between IL-8 level of cord blood, neonatal
      colonization of Ureaplasma, histological chorioamnionitis (CAM), and development
      of CLD was studied. RESULTS: Five infants died and 29 infants developed CLD. The
      CLD group had significantly lower gestation (mean +/- SD: 26.6 +/- 1.8 weeks)
      compared with the infants without CLD (28.9 +/- 1.9 weeks, P < 0.0001). Logistic
      analysis showed that the development of CLD was associated with gestational age
      (odds ratio [OR], 0.5; 95% confidence interval (CI): 0.4-0.8) and Ureaplasma
      colonization (OR, 4.1; 95%CI: 1.2-14.4). Ureaplasma colonization was also
      associated with CAM (OR, 6.5; 95%CI: 1.8-23.5), absence of respiratory distress
      syndrome (OR, 6.2; 95%CI: 1.3-30.5), and development of CLD (OR, 4.0; 95%CI: 1.1
      15.3). Elevated cord blood IL-8 >=100 pg/mL was associated with female sex and
      the isolation of microorganisms (OR, 49.4; 95%CI: 4.6-525). CONCLUSION: The
      development of CLD defined by oxygen requirement at 36 weeks was associated with
      neonatal Ureaplasma colonization but not with IL-8 level of cord blood. Elevated
      cord blood IL-8 was associated with neonatal microorganisms isolation.

PMID- 20136722
TI  - Mothers' depression and health-related quality of life in neuromuscular diseases:
      role of functional independence level of the children.
AB  - BACKGROUND: In the literature there have been studies about quality of life of
      parents who have children with chronic diseases. Most of these studies have
      focused on the stress of parents of children with neuromuscular disease (NMD),
      and there was no evidence to support hypothesized relationships between
      caregiving demands and health-related quality of life (HRQOL). The aim of the
      present study was therefore to evaluate the relations between maternal depression
      and HRQOL and functional limitations of the children with NMD. METHODS: Forty
      children with a diagnosis of NMD and their mothers were included in the study.
      HRQOL of the mothers was assessed on the Turkish version of the Nottingham Health
      Profile (NHP); potential cases of depressive illness were identified on Beck
      Depression Inventory (BDI); and Wee-Functional Independence Measure (Wee-FIM) was
      used to evaluate of functional independence level of the children. RESULTS: It
      was found that mean total NHP score of the mothers was moderately correlated with
      the total FIM score and sphincter control of the child, and weakly correlated
      with the locomotion of the child (P < 0.001). There was moderate correlation
      between mothers' social isolation and children's sphincter control, social
      integration and total Wee-FIM score and a weak correlation between mobility and
      communication scores (P < 0.001). In contrast there was no correlation between
      BDI scores of mothers and Wee-FIM scores of children (P > 0.05). CONCLUSION: The
      functional level of children with NMD is one of the factors that affect the
      quality of life of mothers.

PMID- 20136723
TI  - Relationship between height and blood pressure in Japanese schoolchildren.
AB  - BACKGROUND: Blood pressure examinations for health education use have been
      conducted at several schools in Japan. It has been reported that blood pressure
      is closely associated with bodyweight and height in US children. The aim of the
      present paper was to evaluate the association between height and blood pressure
      in Japanese schoolchildren. METHODS: In Iwata city in Japan, blood pressure
      screening was conducted by the school administration. A total of 98.9%
      (10,152/10,270 children) of all fifth (10-year-olds) and ninth graders (14-year
      olds) residing in the Old Iwata area from 2002 to 2007 were analyzed. RESULTS: In
      10-year-old and 14-year-old boys, regression analysis indicated that a positive
      correlation between weight and blood pressure was the strongest among the three
      body size indices (height, weight, and body mass index), but the association
      between height and blood pressure was also significant. For girls from both the
      10 and 14 year age groups, the correlation of weight and blood pressure was
      stronger than those for the other body size indices, but there were also
      significant associations between height and blood pressure, except for height and
      diastolic blood pressure in the 14-year-olds. CONCLUSIONS: There is a significant
      positive relationship between height and blood pressure. Further study is
      necessary to provide a blood pressure reference based on height in the Japanese
      program to prevent children from developing lifestyle-related risk factors.

PMID- 20136724
TI  - Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD.
AB  - Co-stimulatory molecules expressed on T cells critically regulate donor T-cell
      activation and are implicated in acute GVHD after allogeneic BMT. We here
      investigated the role of interaction between B7-related protein-1 (B7RP-1) and
      ICOS in murine acute GVHD model that received T cell-depleted BM cells and
      splenocytes. Administration of blocking anti-B7RP-1 mAb significantly reduced the
      lethality and symptoms in acute GVHD. A significant hypo-responsiveness of
      splenocytes to host alloantigen was observed in the recipient mice treated with
      anti-B7RP-1 mAb. Moreover, acute GVHD was significantly reduced in the recipients
      of T cells composed of ICOS-deficient CD8 T cells and WT CD4 T cells compared
      with that in the recipients of T cells composed of WT CD8 T cells and ICOS
      deficient CD4 T cells. These results suggested that B7RP-1/ICOS co-stimulatory
      signal plays a role in the activation of alloantigen-reactive donor T cells,
      particularly in CD8 T cells, in murine acute GVHD model, and that the blockade of
      B7RP-1/ICOS interaction may be useful for selectively manipulating allo-reactive
      T cells in the recipients with acute GVHD.

PMID- 20136725
TI  - Long-term remission of recurrent severe anemia as a result of parvovirus B19
      infection in a pediatric renal transplant recipient.
AB  - We studied a case of recurrent PV-B19-associated anemia in a renal transplant
      child with long-term remission induced by baseline immunosuppression adjusted and
      intensive IVIG therapy. This was a 15-yr-old boy. Seven wk after transplantation,
      he experienced acute rejection, which was treated with high-dose steroids, ATG,
      and plasmapheresis. Ten wk after transplantation (three wk after rejection), his
      hemoglobin dropped to 54 g/L and serum PV-B19 PCR was positive. After therapy
      with IVIG and conversion from mycophenolate mofetil to rapamycin, anemia
      resolved. But the patient had fever on the fourth day of IVIG with mild pulmonary
      edema and rise in serum creatinine. Two months after the first course of IVIG,
      anemia recurred and a second course of IVIG (preadministration
      methylprednisolone) was given, which was followed by the resolution of anemia
      without side effect and recurrence two months later again. Baseline
      immunosuppression was adjusted with dual immunosuppression and low doses
      including prednisolone and tacrolimus. At the same time, monthly course of IVIG
      was repeated four times. Within the next 23 months, anemia did not recur and
      renal function remained stable. In conclusion, PV-B19-associated anemia can be
      recurrent in immunocompromised children and baseline immunosuppression should be
      carefully adjusted to control PV-B19 infection.

PMID- 20136726
TI  - Pediatric orthotopic living-donor liver transplantation cures pulmonary
      hypertension caused by Abernethy malformation type Ib.
AB  - A 3.3-yr-old boy was diagnosed with PH caused by a PSS of Abernethy malformation
      type Ib. After control of PH, he underwent OLDLT at 4.9 yr. His PV flowed
      directly into the confluence of the CCLMHV and the IVC. To shorten the anhepatic
      phase, hepatic arterial flow was partially maintained. Removal of the native
      liver began simultaneously with the graft harvest. The proximal PV was cut at the
      optimal point for reconstruction. The distal PV was cut at the concrescence of
      the PV and the CCLMHV. After IVC-plasty, the LHV of the graft was attached with
      an anterior patch by venous grafting and was then anastomosed to the IVC.
      Although the mPAP temporarily increased above the mean arterial pressure, mPAP
      was stable during OLDLT. FNH and steatosis were confirmed histopathologically. In
      summary, pediatric OLDLT was performed successfully in PH caused by PSS.

PMID- 20136727
TI  - ATG8 lipidation and ATG8-mediated autophagy in Arabidopsis require ATG12
      expressed from the differentially controlled ATG12A AND ATG12B loci.
AB  - Autophagic recycling of intracellular plant constituents is maintained at a basal
      level under normal growth conditions but can be induced in response to
      nutritional demand, biotic stress, and senescence. One route requires the
      ubiquitin-fold proteins Autophagy-related (ATG)-8 and ATG12, which become
      attached to the lipid phosphatidylethanolamine (PE) and the ATG5 protein,
      respectively, during formation of the engulfing vesicle and delivery of its cargo
      to the vacuole for breakdown. Here, we genetically analyzed the conjugation
      machinery required for ATG8/12 modification in Arabidopsis thaliana with a focus
      on the two loci encoding ATG12. Whereas single atg12a and atg12b mutants lack
      phenotypic consequences, atg12a atg12b double mutants senesce prematurely, are
      hypersensitive to nitrogen and fixed carbon starvation, and fail to accumulate
      autophagic bodies in the vacuole. By combining mutants eliminating ATG12a/b,
      ATG5, or the ATG10 E2 required for their condensation with a method that
      unequivocally detects the ATG8-PE adduct, we also show that ATG8 lipidation
      requires the ATG12-ATG5 conjugate. Unlike ATG8, ATG12 does not associate with
      autophagic bodies, implying that its role(s) during autophagy is restricted to
      events before the vacuolar deposition of vesicles. The expression patterns of the
      ATG12a and ATG12b genes and the effects of single atg12a and atg12b mutants on
      forming the ATG12-ATG5 conjugate reveal that the ATG12b locus is more important
      during basal autophagy while the ATG12a locus is more important during induced
      autophagy. Taken together, we conclude that the formation of the ATG12-ATG5
      adduct is essential for ATG8-mediated autophagy in plants by promoting ATG8
      lipidation.

PMID- 20136728
TI  - The subcellular distribution of the Arabidopsis histidine phosphotransfer
      proteins is independent of cytokinin signaling.
AB  - Cytokinins are a class of mitogenic plant hormones that play an important role in
      most aspects of plant development, including shoot and root growth, vascular and
      photomorphogenic development and leaf senescence. A model for cytokinin
      perception and signaling has emerged that is similar to bacterial two-component
      phosphorelays. In this model, binding of cytokinin to the extracellular domain of
      the Arabidopsis histidine kinase (AHKs) receptors induces autophosphorylation
      within the intracellular histidine-kinase domain. The phosphoryl group is
      subsequently transferred to cytosolic Arabidopsis histidine phosphotransfer
      proteins (AHPs), which have been suggested to translocate to the nucleus in
      response to cytokinin treatment, where they then transfer the phosphoryl group to
      nuclear-localized response regulators (Type-A and Type-B ARRs). We examined the
      effects of cytokinin on AHP subcellular localization in Arabidopsis and, contrary
      to expectations, the AHPs maintained a constant nuclear/cytosolic distribution
      following cytokinin treatment. Furthermore, mutation of the conserved
      phosphoacceptor histidine residue of the AHP, as well as disruption of multiple
      cytokinin signaling elements, did not affect the subcellular localization of the
      AHP proteins. Finally, we present data indicating that AHPs maintain a
      nuclear/cytosolic distribution by balancing active transport into and out of the
      nucleus. Our findings suggest that the current models indicating relocalization
      of AHP protein into the nucleus in response to cytokinin are incorrect. Rather,
      AHPs actively maintain a consistent nuclear/cytosolic distribution regardless of
      the status of the cytokinin response pathway.

PMID- 20136729
TI  - The role of floral organs in carpels, an Arabidopsis loss-of-function mutation in
      MicroRNA160a, in organogenesis and the mechanism regulating its expression.
AB  - MicroRNAs (miRNAs) have emerged as key regulators of gene expression at the post
      transcriptional level in both plants and animals. However, the specific functions
      of MIRNAs (MIRs) and the mechanisms regulating their expression are not fully
      understood. Previous studies showed that miR160 negatively regulates three genes
      that encode AUXIN RESPONSE FACTORs (ARF10, -16, and -17). Here, we characterized
      floral organs in carpels (foc), an Arabidopsis mutant with a Ds transposon
      insertion in the 3' regulatory region of MIR160a. foc plants exhibit a variety of
      intriguing phenotypes, including serrated rosette leaves, irregular flowers,
      floral organs inside siliques, reduced fertility, aberrant seeds, and viviparous
      seedlings. Detailed phenotypic analysis showed that abnormal cell divisions in
      the basal embryo domain and suspensor led to diverse defects during embryogenesis
      in foc plants. Further analysis showed that the 3' region was required for the
      expression of MIR160a. The accumulation of mature miR160 was greatly reduced in
      foc inflorescences. In addition, the expression pattern of ARF16 and -17 was
      altered during embryo development in foc plants. foc plants were also deficient
      in auxin responses. Moreover, auxin was involved in regulating the expression of
      MIR160a through its 3' regulatory region. Our study not only provides insight
      into the molecular mechanism of embryo development via MIR160a-regulated ARFs,
      but also reveals the mechanism regulating MIR160a expression.

PMID- 20136730
TI  - On why not to rush older adults--relying on reactive cognitive control can
      effectively reduce errors at the expense of slowed responses.
AB  - According to the dual-mechanisms of cognitive control framework (DMC), older
      adults rely predominantly on reactive as opposed to proactive control. As a
      result, we expected elevated response conflict for older relative to younger
      adults with increasing task difficulty. Response-locked ERP activity was examined
      separately for fast and slow responses (representing proactive and reactive
      control, respectively) at low, medium, and high levels of difficulty. Older
      adults recruited reactive control more often than the young, as reflected by
      increased behavioral costs and enhanced pre-response negativity (PRN). No age
      differences in conflict detection (medial frontal negativity, MFN) were evident
      at low levels of difficulty, but response conflict increased along with
      difficulty for older adults. These data provide empirical support for the DMC
      suggesting that aging is associated with a less efficient reactive-control mode
      of processing.

PMID- 20136732
TI  - The interaction of anticipatory anxiety and emotional picture processing: an
      event-related brain potential study.
AB  - The present study examined the interaction of anticipatory anxiety and selective
      emotion processing. Toward this end, a rapid stream of pleasant, neutral, and
      unpleasant pictures was presented in alternating blocks of threat-of-shock or
      safety, which were signaled by colored picture frames. The main finding is that
      pleasant pictures elicited a sustained negative difference potential over
      occipital regions during threat as compared to safety periods. In contrast,
      unpleasant and neutral picture processing did not vary as a function of threat-of
      shock. Furthermore, in both the safety and threat-of-shock conditions, emotional
      pictures elicited an enlarged early posterior negativity and late positive
      potential. These data show that the activation of the fear/anxiety network exerts
      valence-specific effects on affective picture processing. Pleasant stimuli
      mismatching the current state of anticipatory anxiety apparently draw more
      attentional resources.

PMID- 20136731
TI  - Automatic and controlled aspects of lexical associative processing in the two
      cerebral hemispheres.
AB  - Associative processing in the cerebral hemispheres was examined using ERPs and
      visual half-field (VF) methods. Associative strength was manipulated using
      asymmetrically associated pairs: viewed in one order (forward), there was a
      strong prime-to-target association, but in the backward order, predictability was
      weak. N400 priming was greater for forward than backward pairs in both VFs and
      not different across VF, suggesting similar semantic representations and
      automatic meaning activation in the two hemispheres. However, a frontal P2
      enhancement for forward pairs restricted to the LH suggests that it uses context
      to predict likely upcoming words. Also, greater late positive complex priming for
      backward pairs in the LH than the RH reveals a LH advantage for strategically
      reshaping meaning activation for weakly related and/or non-canonically ordered
      pairs. The results link asymmetries in word processing with those observed at the
      sentence level.

PMID- 20136733
TI  - The time line of threat processing and vagal withdrawal in response to a self
      threatening stressor in cognitive avoidant copers: evidence for vigilance
      avoidance theory.
AB  - Using a spatial cueing paradigm with emotional and neutral facial expressions as
      cues, we examined early and late patterns of information processing in cognitive
      avoidant coping (CAV). Participants were required to detect a target that
      appeared either in the same location as the cue (valid) or in a different
      location (invalid). Cue-target onset asynchrony (CTOA) was manipulated to be
      short (250 ms) or long (750 ms). CAV was associated with early facilitation and
      faster disengagement from angry faces. No effects were found for happy or neutral
      faces. After completing the spatial cueing task, participants prepared and
      delivered a public speech and heart rate variability (HRV) was recorded.
      Disengagement from angry faces was related to a decrease in HRV in response to
      this task. Together, these data suggest that CAV is related to early engagement
      followed by disengagement from threat-related cues that might impact
      physiological stress responses.

PMID- 20136734
TI  - Ingroup categorization and response conflict: Interactive effects of target race,
      flanker compatibility, and infrequency on N2 amplitude.
AB  - Three largely independent lines of research have investigated experimental
      manipulations that influence the amplitude of the N2 component of the event
      related brain potential (ERP), one linking heightened N2 amplitude to response
      conflict, another showing that N2 is sensitive to stimulus infrequency, and the
      third showing larger N2 amplitude during categorization of racial ingroup
      relative to racial outgroup targets. The purpose of this research was to
      investigate potential interactions between these three features on the amplitude
      of the N2. ERPs were recorded while participants completed a modified flanker
      task using pictures of ingroup and outgroup faces. Results showed a 3-way
      interaction, indicating that the N2 was largest for ingroup targets on high
      conflict trials but only when such trials were relatively infrequent.
      Implications of these findings for theories of both conflict monitoring and
      person perception are discussed.

PMID- 20136735
TI  - Fast temporal event integration in the visual domain demonstrated by event
      related potentials.
AB  - Four experiments are reported that investigated visual event integration by using
      a variant of the missing element paradigm. Good performance on this task depends
      on whether two brief successive stimulus displays are perceived as (or integrated
      into) one single event. We replicated the classic finding of greater accuracy
      with shorter duration of the first stimulus and ruled out an attention-related
      account thereof. In a subsequent electrophysiological experiment we found that
      successful event integration increased the amplitude of the N1, N2, and late P3
      components of the event-related potential and decreased early P3 amplitude. No
      effect on the P1 was observed. The results provided evidence for an early onset
      of event integration in time and demonstrated the existence of
      electrophysiological markers of episodic integration. The implications of these
      results are related to studies on feature-specific integration and early
      attentional processes.

PMID- 20136737
TI  - Thoracic imaging.
AB  - The various techniques encompassed in the term 'Thoracic Imaging' have had a
      dramatic effect on the practice of respiratory medicine over the last 25 years.
      One of many examples is the increased precision with which lung cancer can be
      preoperatively staged using CT and PET imaging. The increasing sophistication of
      thoracic imaging tests brings many benefits, but there are caveats. This review
      considers a selection of techniques and contains state-of-the-art commentaries by
      distinguished experts on current challenges and likely future developments.

PMID- 20136736
TI  - Obstructive Sleep Apnoea: From pathogenesis to treatment: Current controversies
      and future directions.
AB  - Obstructive sleep apnoea (OSA) is a common disease, recognized as an independent
      risk factor for a range of clinical conditions, such as hypertension, stroke,
      depression and diabetes. Despite extensive research over the past two decades,
      the mechanistic links between OSA and other associated clinical conditions,
      including metabolic disorders and cardiovascular disease, remain unclear. Indeed,
      the pathogenesis of OSA itself remains incompletely understood. This review
      provides opinions from a number of leading experts on issues related to OSA and
      its pathogenesis, interaction with anaesthesia, metabolic consequences and
      comorbidities, cardiovascular disease, genetics, measurement and diagnosis,
      surgical treatment and pharmacotherapeutic targets.

PMID- 20136738
TI  - Statistical evaluation of the New Zealand food safety authority sampling protocol
      for imported food.
AB  - The New Zealand Food Safety Authority sampling protocol for compliance inspection
      of imported food products is evaluated for its ability to provide consumer
      protection. The sampling protocol involves both partial testing of imported
      consignments and complete skipping inspection of consignments based on the
      quality history. The risk posed by the strategies of partial testing and skipping
      inspection of imports is evaluated using the average outgoing quality limit and
      other performance measures. The cost dimension of sampling inspection is also
      considered. Suggestions for improvement, which include tightening the skipping
      inspection parameters, are made.

PMID- 20136739
TI  - Bisphenol a: how the most relevant exposure sources contribute to total consumer
      exposure.
AB  - Bisphenol A (BPA) is an endocrine disrupting chemical that is found in human
      urine throughout industrial societies around the globe. Consumer exposure
      pathways to BPA include packaged food, household dust, air, and dental fillings.
      To date, information on the relative contribution of the different pathways to
      total consumer exposure is lacking, but is key for managing substance-associated
      risks. We investigated the relative contributions of the pathways known to be
      most relevant for nine different consumer groups. Our results suggest that the
      most important pathways for infants and children are the use of polycarbonate
      (PC) baby bottles and for adults and teenagers the consumption of canned food.
      Dental surgery can also considerably contribute over a short time directly after
      the surgery. For infants fed with PC baby bottles with mean dose rates of 0.8
      microg/kg(bw)/d the highest exposure dose rate was calculated. This dose rate is
      far below the tolerable daily intake of 50 microg/kg(bw)/d. However, it is of the
      same order of magnitude as recently reported concentrations that caused low-dose
      health effects in rodents. We find a pattern of falling exposure levels with
      rising age that is supported by urinary concentrations of BPA available for
      selected consumer groups. Similarly, the exposure levels we predict are confirmed
      by the levels reported in these studies.

PMID- 20136740
TI  - A quantitative assessment of the risk for highly pathogenic avian influenza
      introduction into Spain via legal trade of live poultry.
AB  - Highly pathogenic avian influenza (HPAI) is considered one of the most important
      diseases of poultry. During the last 9 years, HPAI epidemics have been reported
      in Asia, the Americas, Africa, and in 18 countries of the European Union (EU).
      For that reason, it is possible that the risk for HPAI virus (HPAIV) introduction
      into Spain may have recently increased. Because of the EU free-trade policy and
      because legal trade of live poultry was considered an important route for HPAI
      spread in certain regions of the world, there are fears that Spain may become
      HPAIV-infected as a consequence of the legal introduction of live poultry.
      However, no quantitative assessment of the risk for HPAIV introduction into Spain
      or into any other EU member state via the trade of poultry has been published in
      the peer-reviewed literature. This article presents the results of the first
      quantitative assessment of the risk for HPAIV introduction into a free country
      via legal trade of live poultry, along with estimates of the geographical
      variation of the risk and of the relative contribution of exporting countries and
      susceptible poultry species to the risk. The annual mean risk for HPAI
      introduction into Spain was estimated to be as low as 1.36 x 10(-3), suggesting
      that under prevailing conditions, introduction of HPAIV into Spain through the
      trade of live poultry is unlikely to occur. Moreover, these results support the
      hypothesis that legal trade of live poultry does not impose a significant risk
      for the spread of HPAI into EU member states.

PMID- 20136741
TI  - A tiered approach for risk-benefit assessment of foods.
AB  - Risk-benefit analyses are introduced as a new paradigm for old problems. However,
      in many cases it is not always necessary to perform a full comprehensive and
      expensive quantitative risk-benefit assessment to solve the problem, nor is it
      always possible, given the lack of required date. The choice to continue from a
      more qualitative to a full quantitative risk-benefit assessment can be made using
      a tiered approach. In this article, this tiered approach for risk-benefit
      assessment will be addressed using a decision tree. The tiered approach described
      uses the same four steps as the risk assessment paradigm: hazard and benefit
      identification, hazard and benefit characterization, exposure assessment, and
      risk-benefit characterization, albeit in a different order. For the purpose of
      this approach, the exposure assessment has been moved upward and the dose
      response modeling (part of hazard and benefit characterization) is moved to a
      later stage. The decision tree includes several stop moments, depending on the
      situation where the gathered information is sufficient to answer the initial risk
      benefit question. The approach has been tested for two food ingredients. The
      decision tree presented in this article is useful to assist on a case-by-case
      basis a risk-benefit assessor and policymaker in making informed choices when to
      stop or continue with a risk-benefit assessment.

PMID- 20136742
TI  - The use of surrogate species in risk assessment: using life history data to
      safeguard against false negatives.
AB  - The use of surrogate species is an important tool in predicting the effects of
      management decisions or the establishment of protective measures for
      endangered/threatened species. While relying on a handful of model species to
      predict the fate of scores of distantly related target species has been
      criticized, a quantitative measure linking life history traits and population
      predictions has been sorely missing. We derive here a closed-form expression
      aimed at determining conditions under which sublethal effects of a toxicant on
      surrogate species population outcomes will reliably predict outcomes of target
      (listed) species. We develop a critical threshold in fecundity reduction above
      which the surrogate species outcomes indicate positive population growth, while
      the listed species is driven to extinction. Thus we have established a means of
      determining conditions under which we are prone to making a "Type II" error in
      assessing ecological risk using surrogate species. Finally, we use the derived
      expression and life history data to compare outcomes from four different commonly
      used fish surrogate species (round goby, fathead minnow, smallmouth bass,
      cutthroat trout) and their target listed species (Chinook and Coho salmon). We
      illustrate that all four surrogate species fail to predict population outcomes
      for the listed species in cases of as little as 15% fecundity reduction due to
      toxicant exposure. Furthermore, surrogate species reliability is a function of
      toxicant level, so that some species are reliable at some levels but not at
      others. We discuss the implications of these findings, and outline further
      analyses that occur as a natural extension of the criteria developed here.

PMID- 20136743
TI  - Risk management and the wisdom of Aldo Leopold.
AB  - Human demands on nature have increased due to our burgeoning population. The
      applications of scientific knowledge to the development of increasingly powerful
      technologies and consumptive lifestyles by more and more people have created a
      modern category of human-caused disaster-stealth disasters. Stealth disasters
      such as agriculturally-induced soil erosion and release of unprecedented amounts
      of greenhouse gases into Earth's atmosphere-tend to have protracted, unobvious
      onsets; do not necessarily have dramatic manifestations; and often do not attract
      public attention until they reach a stage approaching catastrophic consequences.
      At this late stage it is difficult or impossible to undo damage. Scientists tend
      to be among the first to understand the physical causes and notice the
      developments of stealth disasters and their risks and yet scientific knowledge is
      not enough to prevent or mitigate them. As we search for ways to deal with
      stealth disasters, the concept of "land health" assembled by the prominent
      conservationist and author, Aldo Leopold (1887-1948), can, in normative terms,
      provide an ecologically grounded example of nature in good condition toward which
      society can aim. Evidence of the reverse-symptoms of land illness-can provide a
      checklist for risk analysis and management that helps guide people away from harm
      causing attitudes and activities and toward beneficial outcomes. Leopold's
      criteria of land health motivated by a land ethic that incorporates the whole of
      nature may be applied at geographic scales ranging from local to global as a
      framework for contemporary risk management.

PMID- 20136744
TI  - Workers' mental models of chemical exposure in the workplace.
AB  - The objective of this study was to examine workers' mental interpretation models
      developed in response to occupational chemical exposure. The study was performed
      in six companies within the reinforced plastics industry in northern Sweden, in
      which styrene was used; 32 workers participated in the study. Each worker
      performed between four and seven exposure measurements. Before receiving each
      result of the second to seventh measurements, the workers were asked to predict
      the level of their next exposure measurement. Their predictions were evaluated
      with respect to two judgmental principles: coherence (that the predictions are
      based on logical decision rules, that is, the mean value of the prior exposure
      levels); and correspondence (the predictions have high empirical accuracy) by
      calculating the mean absolute percent forcast error (MAPE). The coherence
      principle was tested by comparing each of the workers' predictions with the mean,
      median, and last exposure level (last value) of the prior measurements. The
      correspondence principle was tested by comparing the worker's prediction with the
      outcome of the measurement. The coherence principle was found to be the best
      descriptor of the workers' predictions and the median model had the best fit. The
      mean model had a similar but significantly poorer fit (MAPE values of 29 and 31,
      respectively). The correspondence model had a poor fit with a MAPE of 54. The
      workers' predictions were generally lower than their average exposures. We
      conclude that the workers' interpretation model can be best described by a
      coherence model rather than by a correspondence model.

PMID- 20136745
TI  - General probability-time tradeoff and intertemporal risk-value model.
AB  - This article proposes an intertemporal risk-value (IRV) model that integrates
      probability-time tradeoff, time-value tradeoff, and risk-value tradeoff into one
      unified framework. We obtain a general probability-time tradeoff, which yields a
      formal representation form to reflect the psychological distance of a
      decisionmaker in evaluating a temporal lottery. This intuition of probability
      time tradeoff is supported by robust empirical findings as well as by
      psychological theory. Through an explicit formalization of probability-time
      tradeoff, an IRV model taking into account three fundamental dimensions, namely,
      value, probability, and time, is established. The object of evaluation in our
      framework is a complex lottery. We also give some insights into the structure of
      the IRV model using a wildcatter problem.

PMID- 20136746
TI  - Ensemble habitat mapping of invasive plant species.
AB  - Ensemble species distribution models combine the strengths of several species
      environmental matching models, while minimizing the weakness of any one model.
      Ensemble models may be particularly useful in risk analysis of recently arrived,
      harmful invasive species because species may not yet have spread to all suitable
      habitats, leaving species-environment relationships difficult to determine. We
      tested five individual models (logistic regression, boosted regression trees,
      random forest, multivariate adaptive regression splines (MARS), and maximum
      entropy model or Maxent) and ensemble modeling for selected nonnative plant
      species in Yellowstone and Grand Teton National Parks, Wyoming; Sequoia and Kings
      Canyon National Parks, California, and areas of interior Alaska. The models are
      based on field data provided by the park staffs, combined with topographic,
      climatic, and vegetation predictors derived from satellite data. For the four
      invasive plant species tested, ensemble models were the only models that ranked
      in the top three models for both field validation and test data. Ensemble models
      may be more robust than individual species-environment matching models for risk
      analysis.

PMID- 20136747
TI  - Qualitative risk assessment of the acquisition of Meticillin-resistant
      staphylococcus aureus in pet dogs.
AB  - This article presents a qualitative risk assessment of the acquisition of
      meticillin-resistant Staphylococcus aureus (MRSA) in pet dogs, representing an
      important first step in the exploration of risk of bidirectional MRSA transfer
      between dogs and humans. A conceptual model of the seven potential pathways for
      MRSA acquisition in a dog in any given 24-hour period was developed and the data
      available to populate that model were considered qualitatively. Humans were found
      to represent the most important source of MRSA for dogs in both community and
      veterinary hospital settings. The environment was found to be secondary to humans
      in terms of importance and other dogs less still. This study highlights some
      important methodological limitations of a technique that is heavily relied upon
      for qualitative risk assessments and applies a novel process, the use of relative
      risk ranking, to enable the generation of a defensible output using a matrix
      combination approach. Given the limitations of the prescribed methods as applied
      to the problem under consideration, further validation, or repudiation, of the
      findings contained herein is called for using a subsequent quantitative
      assessment.

PMID- 20136748
TI  - Individual actual or perceived property flood risk: did it predict evacuation
      from Hurricane Isabel in North Carolina, 2003?
AB  - Individual perception of risk has consistently been considered an important
      determinant of hurricane evacuation in published studies and reviews. Adequate
      risk assessment is informed by environmental and social cues, as well as
      evacuation intentions and past disaster experience. This cross-sectional study
      measured perceived flood risk of 570 residents of three coastal North Carolina
      counties, compared their perception with actual risk determined by updated flood
      plain maps, and determined if either was associated with evacuation from
      Hurricane Isabel in 2003. Census blocks were stratified by flood zone and 30
      census blocks were randomly selected from each flood zone. Seven interviews were
      conducted at random locations within selected blocks. Bivariate and multivariable
      analyses were conducted to produce crude and adjusted risk differences. Neither
      the designated flood zone of the parcel where the home was located nor the
      residents' perceived flood risk was associated with evacuation from Hurricane
      Isabel in the bivariate analysis. In the multivariable analysis, intention to
      evacuate and home type were important confounders of the association between
      actual risk and evacuation. The belief that one is at high risk of property
      damage or injury is important in evacuation decision making. However, in this
      study, while coastal residents' perceived risk of flooding was correlated with
      their actual flood risk, neither was associated with evacuation. These findings
      provide important opportunities for education and intervention by policymakers
      and authorities to improve hurricane evacuation rates and raise flood risk
      awareness.

PMID- 20136749
TI  - Assessing potential human health hazards and benefits from subtherapeutic
      antibiotics in the United States: tetracyclines as a case study.
AB  - Many scientists, activists, regulators, and politicians have expressed urgent
      concern that using antibiotics in food animals selects for resistant strains of
      bacteria that harm human health and bring nearer a "postantibiotic era" of
      multidrug resistant "super-bugs." Proposed political solutions, such as the
      Preservation of Antibiotics for Medical Treatment Act (PAMTA), would ban entire
      classes of subtherapeutic antibiotics (STAs) now used for disease prevention and
      growth promotion in food animals. The proposed bans are not driven by formal
      quantitative risk assessment (QRA), but by a perceived need for immediate action
      to prevent potential catastrophe. Similar fears led to STA phase-outs in Europe a
      decade ago. However, QRA and empirical data indicate that continued use of STAs
      in the United States has not harmed human health, and bans in Europe have not
      helped human health. The fears motivating PAMTA contrast with QRA estimates of
      vanishingly small risks. As a case study, examining specific tetracycline uses
      and resistance patterns suggests that there is no significant human health hazard
      from continued use of tetracycline in food animals. Simple hypothetical
      calculations suggest an unobservably small risk (between 0 and 1.75E-11 excess
      lifetime risk of a tetracycline-resistant infection), based on the long history
      of tetracycline use in the United States without resistance-related treatment
      failures. QRAs for other STA uses in food animals also find that human health
      risks are vanishingly small. Whether such QRA calculations will guide risk
      management policy for animal antibiotics in the United States remains to be seen.

PMID- 20136750
TI  - Isolated hip and ankle fatigue are unlikely risk factors for anterior cruciate
      ligament injury.
AB  - Lower extremity neuromuscular fatigue purportedly increases anterior cruciate
      ligament (ACL) injury risk through promotion of extreme landing mechanics.
      However, the impact of fatigue on muscle groups critical to the landing strategy
      remains unclear. This study examined the effects of isolated hip rotator and
      triceps surae fatigue on lower extremity landing biomechanics. Sixteen healthy
      females (18-22 years) reported for testing on two occasions, with one muscle
      group fatigued per session. Subjects performed three single-leg landings onto a
      force platform pre- and post-fatigue, defined as an 80% decrease in peak torque
      in the targeted muscle group. Hip rotator fatigue was induced via alternating
      concentric contractions and triceps surae fatigue through concentric plantar
      flexion contractions on an isokinetic dynamometer. Initial contact (IC)
      kinematics and peak stance (PS) kinetics and kinematics were analyzed pre- and
      post-fatigue. Hip rotator fatigue increased IC (P=0.05) and PS (P=0.04) hip
      internal rotation angles. Triceps surae fatigue decreased IC knee flexion
      (P=0.01) angle. Isolated hip rotator and triceps surae fatigue each produced
      modifications in lower limb kinematic parameters viewed as risk factors for ACL
      injury. These modifications, however, do not appear of sufficient magnitude to
      compromise ligament integrity, suggesting injury via an integrative lower
      extremity fatigue mechanism is more likely.

PMID- 20136751
TI  - The effect of heavy strength training on muscle mass and physical performance in
      elite cross country skiers.
AB  - AIM: To investigate the effect of supplementing high-volume endurance training
      with heavy strength training on muscle adaptations and physical performance in
      elite cross country skiers. Eleven male (18-26 years) and eight female (18-27
      years) were assigned to either a strength group (STR) (n=9) or a control group
      (CON) (n=10). STR performed strength training twice a week for 12 weeks in
      addition to their normal endurance training. STR improved 1 repetition maximum
      (RM) for seated pull-down and half squat (19 +/- 2% and 12 +/- 2%, respectively),
      while no change was observed in CON. Cross-sectional area (CSA) increased in m.
      triceps brachii for both STR and CON, while there was no change in the m.
      quadriceps CSA. VO(2max) during skate-rollerskiing increased in STR (7 +/- 1%),
      while VO(2max) during running was unchanged. No change was observed in energy
      consumption during rollerskiing at submaximal intensities. Double-poling
      performance improved more for STR than for CON. Both groups showed a similar
      improvement in rollerski time-trial performance. In conclusion, 12 weeks of
      supplemental heavy strength training improved the strength in leg and upper body
      muscles, but had little effect on the muscle CSA in thigh muscles. The
      supplemental strength training improved both VO(2max) during skate-rollerskiing
      and double-poling performance.

PMID- 20136752
TI  - Physical self-perception and motor performance in normal-weight, overweight and
      obese children.
AB  - The aim of this study was to examine the relationships among physical self
      perception, body image and motor performance in Italian middle school students.
      Two hundred and sixty children were categorized into normal-weight (n=103),
      overweight (n=86) or obese (n=71) groups. Perceived coordination, body fat and
      sports competence were assessed using the Physical Self-Description
      Questionnaire, while body image was measured using Collins' Child Figure
      Drawings. Individuals' perceptions of strength, speed and agility were assessed
      using the Perceived Physical Ability Scale. Tests involving the standing long
      jump, 2 kg medicine-ball throw, 10 * 5 m shuttle-run and 20 and 30 m sprints were
      also administered. Girls, when compared with boys, and overweight and obese
      participants, when compared with normal-weight peers, reported lower perceived
      and actual physical competence, higher perceived body fat and greater body
      dissatisfaction. Body dissatisfaction mediated all the associations between body
      mass index (BMI) and the different aspects of physical self-perception in boys,
      but not in girls. The same pattern of results was found for physical self
      perception as a mediator of the relationship between BMI and body
      dissatisfaction. In conclusion, obesity proved to have adverse effects on both
      motor performance and physical self-perception.

PMID- 20136753
TI  - The KorperkoordinationsTest fur Kinder: reference values and suitability for 6-12
      year-old children in Flanders.
AB  - An adequate coordination level in children is important for their general
      development, but also for health, psychosocial, academic and well-being-related
      reasons. In this study, the suitability of the KorperkoordinationsTest fur Kinder
      (KTK) as an assessment instrument for the gross motor coordination was evaluated
      in 2470 children from 26 elementary schools for general education spread over the
      Flemish and Brussels-capital region. All children performed four subtests:
      walking backwards (WB), moving sideways (MS), hopping for height (HH) and jumping
      sideways (JS). Age and gender-specific values were established for the Flemish
      children anno 2008. Overall, the current sample scored significantly worse than
      their 1974 German counterparts (P<0.001). Score distribution showed 21% of the
      children being placed in the problematic range of gross motor coordination level.
      A decline in coordination was observed especially in those tasks relying
      primarily on coordinative capacities (WB and MS), while improvements or status
      quo in those tasks relying on strength and speed (JS and HH) were explained by
      secular trends. We suggest that the KTK is a valuable instrument for the
      assessment of the gross motor coordination of Flemish children and efforts should
      be made in order to face the decline in coordination.

PMID- 20136754
TI  - Effects of Darbepoetin Alfa with exercise in cancer patients undergoing
      chemotherapy: an explorative study.
AB  - Fatigue is frequent in cancer patients undergoing chemotherapy. Erythropoietins
      (EPO) have shown well-documented effects on these patients, and administered in
      pharmacological doses, may reduce the need for transfusion of blood cells and
      improve quality of life (QoL). An explorative, descriptive, non-randomised
      intervention study using semi-structured interviews was conducted with the aim to
      gain an insight into the effects and experiences associated with EPO treatment in
      combination with a structured 6-week physical exercise intervention. Sixteen
      cancer patients with evidence of disease, who had received at least one cycle
      chemotherapy, participated. Participants received 500 MUg Darbepoetin Alfa (DA)
      every 3 weeks during the intervention. Four typologies of patients were
      identified with regard to DA effects. The interviews revealed that eleven
      patients experienced some kind of immediate improvement in cognitive and
      emotional functioning, and subjective daily well-being. Furthermore physical
      improvement and changes in QoL outcomes showed no significant differences between
      the study group and a reference group. A significant increase in the hemoglobin
      concentration (7.14-7.87 mmol/L, P<0.05) was found in the study group. The future
      use of EPO in cancer patients is hampered by the reported negative influence of
      EPO on the prognosis in some diagnoses and should be based on randomized studies.

PMID- 20136755
TI  - Exploring exercise behavior, intention and habit strength relationships.
AB  - The purpose of this study was to explore the relevance of integrating exercise
      habit strength within the framework of the theory of planned behavior. Data were
      obtained from 538 undergraduate students [mean age=21.19 (SD=2.57); 28.4% males]
      using validated questionnaires and analyzed using regression analysis and
      discriminant function analysis. Findings indicated that exercise has both a
      cognitive and an automatic component and that stronger exercise habits make
      exercise less intentional, with the intention-exercise relationship nearly three
      times stronger at lower levels of exercise habit strength than at higher levels.
      Further, outcome expectancies regarding health and weight management resulting
      from sufficient exercise did not significantly differ between most profiles that
      were created from exercise behavior, motivation and habit strength. The results
      from this study demonstrate the usefulness of incorporating measures of exercise
      habit strength in order to further our understanding of relevant determinants of
      exercise behavior. Results also indicate that health outcomes of sufficient
      exercise are generally well known, implying that persuasive strategies should
      rather shift in emphasis toward instilling a sense of exercise confidence in
      various situations. This potentially valuable information may allow for a more
      thorough understanding of exercise determinants and the development of more
      effective interventions that target increased exercise levels.

PMID- 20136756
TI  - Long-term clinical and radiological assessment of untreated severe cartilage
      damage in the knee: a natural history study.
AB  - We aimed to evaluate whether and to what extent an isolated deep cartilage lesion
      localized within the tibiofemoral and the patellofemoral joint has an impact on
      the clinical outcomes and osteoarthritis (OA) progression when it is left
      untreated. From 1991 to 1994, 4121 consecutive knee arthroscopies were performed,
      and 37 of them in patients with a single isolated chondral lesion of Outerbridge
      grade 4 located within weight-bearing areas of the femoral and tibial condyles
      (FT group) and patella (P group). The lesion size ranged from 2 to 4 cm(2) .
      Outcomes were reported at a mean 15.3-year follow-up using the Lysholm score, the
      Tegner activity scale and the Womac score. The mean Lysholm, Tegner and Womac
      score in the FT group was 87.7, 5.6 and 88.7, respectively. In the P group, it
      was 83.8, 4.8 and 84.6, respectively (P<0.0.5). Osteoarthritic changes were found
      in 39% of the patients. There was no difference in OA severity between an injured
      and an uninjured knee. In patients of the FT group, there was a relationship
      between the incidence of tibiofemoral OA and patellofemoral OA (P=0.00075).
      Severe isolated single chondral damage left with no treatment has a limited
      influence on clinical outcomes and the development of OA.

PMID- 20136757
TI  - Post-exercise aortic hemodynamic responses to low-intensity resistance exercise
      with and without vascular occlusion.
AB  - High-intensity resistance exercise may acutely increase arterial stiffness.
      Vascular occlusion (VO) acutely decreases arterial stiffness. The purpose of this
      study was to evaluate acute aortic hemodynamic responses to low-intensity
      resistance exercise (LIRE) with slow eccentric movement with and without VO.
      Twenty-three young healthy subjects (12 women and 11 men) were randomized into
      three trials: seated control (CON), LIRE (six sets at 40% one repetition
      maximum), and LIRE with VO. Vascular measurements were assessed before,
      immediately (post1), and 30 min after (post30) each trial. There were significant
      (P<0.05) time effects and trial-by-time interactions such that the changes were
      greater after the LIRE trials compared with CON. Aortic blood pressure [systolic
      (~10 mmHg) and diastolic (~5 mmHg)], heart rate (~23 b.p.m.), and the first (~10
      mmHg) and second systolic peak (~9 mmHg) increased, whereas time to reflection
      decreased (~15 ms) at post1. All measurements returned to baseline at post30,
      except aortic augmentation index (AIx), which decreased ~5% after the LIRE trials
      compared with CON. Increases in cardiovascular variables immediately after the
      LIRE trials were mild and short lasting. Our results indicate that LIRE acutely
      decreases AIx 30 min after exercise cessation. The use of moderate intermittent
      VO during LIRE does not produce additional post-exercise vascular effects.

PMID- 20136758
TI  - Relative age is associated with sport dropout: evidence from youth categories of
      French basketball.
AB  - The aim of the current research was to investigate the relative age effect (RAE)
      as a factor of basketball dropout. In order to do so, we examined the
      distribution of birth dates of young male (n=44,498) and female (n=30,147) French
      basketball players who have dropped out this sport during or at the end of the
      2005-2006 season. chi(2) analyses showed an underrepresentation of dropouts among
      male players born early in the competition year and an overrepresentation among
      those born late in the "9-10 years old,""11-12 years old," and "13-14 years old"
      categories and in the first year of the "15-17 years old" category. Concerning
      girls, this asymmetry was observed across the same age categories. For both boys
      and girls, there was no biased distribution in the "7-8 years old" category.
      Findings of the present study confirm that the RAE should be taken into
      consideration in studies about sport dropout as a variable that may influence
      this phenomenon significantly.

PMID- 20136759
TI  - Psychological predictors of sport injuries among junior soccer players.
AB  - Previous researches have established models that specify psychological factors
      that could predict sport injuries. One example is Williams and Andersen's stress
      injury model stressing factors such as anxiety, negative life stress and few
      coping resources. The purpose of the current study was to find psychological
      factors that could lead to an increased injury risk among junior soccer players,
      in addition to construct an empirical model of injury risk factors for soccer
      players. The participants were 108 male and female soccer players (m=17, 6)
      studying at soccer high schools in southwest Sweden. Five questionnaires were
      used, State Trait Anxiety Inventory, Sport Anxiety Scale, Life Events Survey for
      Collegiate Athletes, Athletic Coping Skills Inventory-28 and Swedish universities
      Scales of Personality. Injury record was collected by athletic trainers at the
      schools during a period of 8 months. The result suggested four significant
      predictors that together could explain 23% of injury occurrence. The main factors
      are life event stress, somatic trait anxiety, mistrust and ineffective coping.
      These findings partly support Williams and Andersen's stress-injury model and are
      organized into an empirical model. Recommendations are given to sport medicine
      teams and coaches concerning issues in sport injury prevention.

PMID- 20136760
TI  - Predictors of functional capacity and skill in youth soccer players.
AB  - Predictors of functional capacities and skills in 143 soccer players aged 11-14
      years from five clubs in Portugal were investigated. Data for players aged 11-12
      (n=75) and 13-14 (n=68) years included chronological age, skeletal age, stage of
      pubic hair (PH), anthropometry, four functional capacities, four soccer skills
      and experience; composite functional and skill scores were derived. Multiple
      linear regression analysis was used to examine the independent effects of age,
      maturity, body size and proportions, adiposity and experience on individual
      functional capacities and skills and composite scores. Explained variances
      differed among functional capacities (22-48%) and skills (<25%), and were greater
      for composite functional (younger 37%, older 58%) than skill (younger 26%, older
      18%) scores. Skeletal maturity was a predictor of the counter-movement jump in
      both groups and of composite functional and skill scores in older players. Age
      and adiposity were primary predictors in players aged 11-12 years, while
      experience and a proportionally longer trunk (conversely, relatively shorter
      lower extremities) appeared among predictors in players aged 13-14 years. PH was
      not among predictors. Except for the counter-movement jump, predictors of
      functional capacities and soccer skills differed between age groups.

PMID- 20136761
TI  - Fluid balance, thermoregulation and sprint and passing skill performance in
      female soccer players.
AB  - Ten females performed 90 min of the Loughborough Intermittent Shuttle Test (LIST)
      on two occasions separated by 7 days. Water [3 mL/kg body mass (BM)] was provided
      every 15 min during exercise (FL); no fluid was given in the other trial (NF).
      Participants performed the Loughborough Soccer Passing Test (LSPT) before and
      every 15 min during the LIST. Core temperature (T(c) ) was measured throughout
      using ingestible temperature sensors. Heart rate (HR), blood lactate ([La(-) ])
      and ratings of perceived exertion (RPE) were collected at regular intervals
      during exercise. Participants experienced greater BM loss in NF (2.2 +/- 0.4%)
      than FL (1.0 +/- 0.4%; P<0.001). Sprint performance deteriorated by 2.7% during
      exercise (P<0.001) but there was no difference between trials (P=0.294). No
      significant differences in LSPT performance were detected between trials
      (P=0.31). T(c) was higher during exercise in NF and was 38.6 +/- 0.3  degrees C
      (NF) and 38.3 +/- 0.3  degrees C (FL; P<0.01) after 90 min. HR (P<0.001), [La(-)
      ] (P<0.01) and RPE (P=0.009) were higher during exercise in NF. Ingesting water
      during a 90-min match simulation reduces the mild dehydration seen in female
      soccer players when no fluid is consumed. However, there was no effect of fluid
      ingestion on soccer passing skill or sprint performance.

PMID- 20136762
TI  - Echocardiographic evaluation of aged male cross country skiers.
AB  - The aim of this echocardiographic study was to evaluate the effects of long-term
      endurance training on cardiac structure and function in three different age
      groups of 48 healthy middle-aged and old former or still active male cross
      country skiers (23 in age group I: age 58.6 +/- 2.2 years; 21 in age group II:
      age 74.9 +/- 2.2 years; four in age group III: age 89.5 +/- 1.9 years). The two
      oldest age groups were combined and compared with age group I. No significant
      differences in left atrial or ventricular dimensions between these two age groups
      were found. A high proportion of enlarged left atrial dimensions were found among
      all subjects with 80% exceeding the upper reference limit of 40 mm in diameter
      (LADs) and 94% exceeding the upper reference limit of 20 cm(2) in area (LAAs).
      Mean values for LADs (mm) and LAAs (cm(2) ) were: group I: 41.9 +/- 4.7 and 24.7
      +/- 3.3; group II: 43.5 +/- 4.8 and 25.2 +/- 3.7; group III: 44.5 +/- 4.7 and
      25.8 +/- 3.7. Left ventricular diastolic diameter exceeded the upper reference
      limits of >54 mm in 20 subjects among all. The groups had preserved systolic and
      age-related diastolic function.

PMID- 20136763
TI  - Effects of socioeconomic status on the physical activity in adolescents: a
      systematic review of the evidence.
AB  - The relationship between physical activity and socioeconomic status (SES) is
      evident in the adult population, but is much discussed with regard to
      adolescents. The main objective of this review was, therefore, to clarify whether
      there is a relationship between physical activity and SES in adolescents.
      Computerized searches were conducted in the databases PubMed, ISI Web of
      knowledge and SPORT-Discus to identify all relevant articles up to July 2009.
      Other review articles, descriptive or theoretical articles and articles where the
      adolescents in the samples were outside the age group of 13-18 years were
      excluded. Sixty-two articles were included in the end. The main results support
      the hypothesis that there is an association between SES and physical activity
      among adolescents, and that adolescents with higher SES are more physically
      active than those with lower SES. The findings are, however, far from uniform.
      Forty-two percent of the included studies report no or an opposite relation.
      There is also an inconsistent use of measures for both variables that complicates
      explanations and interpretations of the findings. This fortifies the claim that
      there is no single explanation for a possible difference in physical activity
      between different socioeconomic groups.

PMID- 20136764
TI  - Effects of a 12-week intervention period with football and running for habitually
      active men with mild hypertension.
AB  - The present study examined the effect of football (F, n=15) training on the
      health profile of habitually active 25-45-year-old men with mild hypertension and
      compared it with running (R, n=15) training and no additional activity (controls,
      C, n=17). The participants in F and R completed a 1-h training session 2.4
      times/week for 12 weeks. Systolic and diastolic blood pressure decreased in all
      groups but the decrease in diastolic blood pressure in F (-9 +/- 5 (+/- SD) mmHg)
      was higher than that in C (-4 +/- 6 mmHg). F was as effective as R in decreasing
      body mass (-1.6 +/- 1.8 vs-1.5 +/- 2.1 kg) and total fat mass (-2.0 +/- 1.5 vs 
      1.6 +/- 1.5 kg) and in increasing supine heart rate variability, whereas no
      changes were detected for C. Maximal stroke volume improved in F (+13.1%) as well
      as in R (+10.1%) compared with C (-4.9%). Total cholesterol decreased in F (5.8
      +/- 1.2 to 5.5 +/- 0.9 mmol/L) but was not altered in R and C. We conclude that
      football training, consisting of high-intensity intermittent exercise, results in
      positive effects on blood pressure, body composition, stroke volume and supine
      heart rate variability, and elicits at least the same cardiovascular health
      benefits as continuous running exercise in habitually active men with mild
      hypertension.

PMID- 20136765
TI  - Improvement of systolic and diastolic heart function after physical training in
      sedentary women.
AB  - The present study examined the cardiac effects of football training and running
      for inactive pre-menopausal women by standard echocardiography and tissue Doppler
      imaging. Thirty-seven subjects were randomized to two training groups (football:
      FG; n=19; running; RG; n=18) training 1 h with equal average heart rates twice a
      week for 16 weeks and compared with a matched inactive control group (CG; n=10).
      During the training period, left ventricular end-diastolic volume increased by
      13% in FG and 11% in RG (P<0.05). Left ventricular posterior wall thickness
      increased in FG from 8.5+/-1.4 to 9.0+/-1.3 mm (P<0.05). Right ventricle diameter
      increased by 12% in FG and 10% in RG (P<0.05). Tissue Doppler imaging
      demonstrated increased left ventricular systolic and diastolic performances in
      both training groups. Peak systolic velocity increased by 26% in FG and 17% in RG
      (P<0.05) and left ventricular longitudinal displacement increased in both groups
      by 13% (P<0.05). Isovolumetric relaxation time decreased significantly more in FG
      than in RG (26% vs 14%, respectively P<0.05). In conclusion, 16 weeks of football
      and running exercise training induced significant changes of cardiac dimensions
      and had favorable effects on both left ventricular systolic and diastolic
      function. These training-induced cardiac adaptations appeared to be more
      consistent after football training compared with running.

PMID- 20136766
TI  - Football to tackle overweight in children.
AB  - The present study aimed at analyzing the efficacy of a 6-month football training
      program compared with a standard exercise program on health and fitness
      parameters in overweight children. The study design was a 6-month, two-arm,
      parallel-group randomized trial. Twenty-two overweight children were randomly
      assigned to two groups (age=10.8+/-1.2 years, height=1.56+/-0.08 m, weight=
      65.1+/-11.4 kg). One group conducted a football training program, and the other
      group an established standard sports program. Both interventions took place three
      times per week from mid-May to mid-November. Before, after 3 months and after the
      training period, comprehensive testing was conducted: anthropometric
      characteristics, cycling ergometry, psychometric monitoring as well as several
      motor ability tests. Maximal performance capacity increased and submaximal heart
      rate during cycling ergometry decreased significantly. Several motor skills as
      well as self-esteem also improved considerably. Body composition and other
      psychometric variables remained nearly unchanged. No relevant differences were
      observed between both exercise programs. It can be concluded that a 6-month
      football training is as efficacious in improving the physical capacity, health
      related fitness parameters and self-esteem of overweight children as a standard
      exercise program. These results provide further evidence that playing football
      has significant health effects.

PMID- 20136768
TI  - Nomenclature for factors of the HLA system, update October 2009.

PMID- 20136769
TI  - Nomenclature for factors of the HLA system, update November 2009.

PMID- 20136770
TI  - HA-1 and HA-2 minor histocompatibility antigens in Tunisians.
AB  - Minor histocompatibility antigens (MiHAgs), such as HA-1 and HA-2, are the main
      targets of immune responses after allogeneic stem cell transplantation (SCT). HA
      1 and HA-2 are two hematopoietic system-restricted antigens encoded,
      respectively, by HMHA1 and MYO1G genes. In order to estimate their frequencies in
      Tunisians, we performed a molecular-based allele analysis for 160 healthy and
      unrelated subjects. Genomic DNAs were extracted mainly by the salting out method.
      Single nucleotide polymorphism (SNP) genotyping assays for selected sites at
      HMHA1 gene (rs3764653 and rs1801284) and at MYO1G gene (rs61739531) were
      performed with a sequence specific primers-polymerase chain reaction (SSP-PCR)
      method. Statistical analysis of our results showed that the HA-2 antigen is more
      frequent than the HA-1 antigen in the Tunisian population because their
      frequencies were 97% and 57%, respectively. Allele analysis for HMHA1 gene showed
      that the R variant (500T-504G) was predominant in our population (64%). For the
      MYO1G gene, the C allele was predominant (84%). All loci were in Hardy-Weinberg
      equilibrium (minimum P value = 0.06). Our frequencies were close to those
      reported in African and Caucasian groups.

PMID- 20136771
TI  - A new era for T-cell immune function assays in transplantation.
AB  - Cellular assays have been used to assess the pre- and post-transplant immune
      status of recipients throughout the history of clinical transplantation.
      Initially, bulk culture assays were used; however, more recent refinements in the
      techniques allow for assaying multiple functions simultaneously including cell
      subset functional analysis and the response at the single cell level. The
      intracellular ATP synthesis assay is being incorporated routinely into the
      clinical testing strategy. Both donor-specific and non-specific testing
      strategies are being used to evaluate the immune status of recipients allowing
      for potential points of intervention aimed at decreasing the adverse impact of
      clinical complications. This review focuses on the current use of cellular
      testing in clinical transplantation.

PMID- 20136772
TI  - Association of a dog leukocyte antigen class II haplotype with
      hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers.
AB  - Canine hypoadrenocorticism (Addison's disease) is due to a deficiency of
      corticosteroids and mineralocorticoids produced by the adrenals. Although this is
      a relatively uncommon disease in the general dog population, some breeds,
      including the Nova Scotia Duck Tolling Retriever (NSDTR), are at increased risk
      for developing hypoadrenocorticism. A prior study has shown that the increased
      risk is due to a heritable component. This potentially lethal disorder is
      hypothesized to have an autoimmune etiology, thus the aim of this study was to
      determine whether genetic susceptibility to hypoadrenocorticism in NSDTRs is
      associated with genes of the canine major histocompatibility complex [MHC; dog
      leukocyte antigen system (DLA)]. Samples were collected from NSDTRs diagnosed
      with hypoadrenocorticism and healthy siblings or country-matched controls. The
      DLA class II alleles and haplotypes were determined and compared between cases
      and controls. We found seven different haplotypes of which the haplotype DLA
      DRB1*01502/DQA*00601/DQB1*02301 was significantly more prevalent in the diseased
      dogs (P = 0.044). In addition, these affected dogs also were more likely to be
      homozygous across the DLA class II region than the control dogs (OR = 6.7, CI =
      1.5-29.3, P = 0.011). We also found that homozygous dogs, regardless of their
      haplotype, tended to have earlier disease onset compared with heterozygous dogs.
      These data indicate a limited MHC diversity in North American NSDTRs and suggest
      that the MHC may play a role in the development of hypoadrenocorticism in the
      NSDTR, supporting the autoimmune origin of the disease.

PMID- 20136773
TI  - HLA class II polymorphisms in Tunisian patients with dilated cardiomyopathy.
AB  - Cardiomyopathies (CMs) are primary disorders of cardiac muscle. They are a major
      cause of morbidity and mortality for all ages and, like acquired forms of
      cardiovascular disease, often result in heart failure. Molecular genetic studies
      have made remarkable progress in defining the pathogenesis of CM. The present
      study was the first report to evaluate the relationship between class II major
      histocompatibility complex (MHC) genes (HLA-DRB1 and HLA-DQB1) and the genetic
      susceptibility to primary dilated cardiomyopathy (DCM) in Tunisian patients. The
      human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed in 76 patients
      with primary DCM and 111 ethnically matched healthy controls using polymerase
      chain reaction-sequence specific primers technique. An increased frequencies of
      HLA-DRB1*0401 (OR = 2.67, P < 0.001), HLA-DQB1*0302 (OR = 3.28, P = 0.001) and
      HLA-DQB1*0401 (OR = 6.26, P = 0.005) alleles were found in the patients with
      primary DCM compared with healthy controls. Individuals with HLA-DRB1*1301 (OR =
      0.24, P < 0.001) and HLA-DQB1*0201 (OR = 0.49, P = 0.002) alleles have a
      protective effect against primary DCM. Two haplotypes were associated with
      increased risk of primary DCM: DRB1*0401/DQB1*0302 (OR = 4.53, P = 0.002) and
      DRB1*0401/DQB1*0401 (OR = 9.42, P = 0.004). In conclusion, our data suggest that
      the variation in class II HLA alleles could be a genetic factor involved in the
      susceptibility to primary DCM in the Tunisian population.

PMID- 20136774
TI  - Polymorphism of human CD1a, CD1d, and CD1e in exon 2 in Chinese Han and She
      ethnic populations.
AB  - CD1 molecules are the major histocompatibility complex (MHC)-like glycoproteins
      specialized in capturing and presenting a variety of glycolipid to antigen
      specific T-cells. There are five closely linked CD1 genes termed as CD1a, CD1b,
      CD1c, CD1d, and CD1e. CD1 gene features limited the polymorphism in exon 2 which
      encodes for the alpha1 domain. Few investigations on the allele frequencies of
      the CD1 genes have been reported to date; however, variation of CD1 allele
      frequency in different ethnics has been observed. In the current study, the CD1a,
      CD1d, and CD1e gene polymorphisms in exon 2 (alleles 01 and 02) in a group of
      normal Chinese Han and She individuals were analyzed. Similar allele prevalence
      was observed between the two populations. The CD1e allele frequency was 37.1%
      (allele 01); 62.9% (allele 02) and 39.3% (allele 01); 60.7% (allele 02) for Han
      and She populations, respectively. CD1e was the only polymorphic gene with a
      genotype frequency for Chinese Han (01/01, 11.0%; 01/02, 52.2%; 02/02, 36.8%) and
      She (01/01, 13.2%; 01/02, 52.1%; 02/02, 34.7%) individuals, respectively. No CD1a
      allele 01 and CD1d allele 02 were observed in either population. Our findings
      indicate that the polymorphism of CD1a, CD1d, and CD1e genes in exon 2 is very
      limited in the Chinese Han and She ethnics.

PMID- 20136775
TI  - Haplotype-specific sequencing reveals a novel HLA-A*03 allele, A*030114.
AB  - The novel allele HLA-A*030114 differs from HLA-A*03010101 by a silent nucleotide
      substitution at codon 153A (GCG to GCA).

PMID- 20136776
TI  - Cellular internalization of exosomes occurs through phagocytosis.
AB  - Exosomes play important roles in many physiological and pathological processes.
      However, the exosome-cell interaction mode and the intracellular trafficking
      pathway of exosomes in their recipient cells remain unclear. Here, we report that
      exosomes derived from K562 or MT4 cells are internalized more efficiently by
      phagocytes than by non-phagocytic cells. Most exosomes were observed attached to
      the plasma membrane of non-phagocytic cells, while in phagocytic cells these
      exosomes were found to enter via phagocytosis. Specifically, they moved to
      phagosomes together with phagocytic polystyrene carboxylate-modified latex beads
      (biospheres) and were further sorted into phagolysosomes. Moreover, exosome
      internalization was dependent on the actin cytoskeleton and phosphatidylinositol
      3-kinase, and could be inhibited by the knockdown of dynamin2 or overexpression
      of a dominant-negative form of dynamin2. Further, antibody pretreatment assays
      demonstrated that tim4 but not tim1 was involved in exosomes uptake. We also
      found that exosomes did not enter the internalization pathway involving caveolae,
      macropinocytosis and clathrin-coated vesicles. Our observation that the cellular
      uptake of exosomes occurs through phagocytosis has important implications for
      exosome-cell interactions and the exosome intracellular trafficking pathway.

PMID- 20136777
TI  - Regulation of ER-Golgi intermediate compartment tubulation and mobility by COPI
      coats, motor proteins and microtubules.
AB  - Little is known about the formation and regulation of endoplasmic reticulum (ER)
      Golgi transport intermediates, although previous studies suggest that cargo is
      the main regulator of their morphology. In this study, we analyze the role of
      coat protein I (COPI) and cytoskeleton in the formation of tubular ER-Golgi
      intermediate compartment (ERGIC) and also show that partial COPI detachment by
      means of low temperature (15 degrees C) or brefeldin A induces the formation of
      transient tubular ERGIC elements. Most of them moved from the cell periphery to
      the perinuclear area and were 2.5x slower than vesicles. Time-lapse analysis of
      living cells demonstrates that the ERGIC elements are able to shift very fast
      from tubular to vesicular forms and vice versa, suggesting that the amount of
      cargo is not the determining factor for ERGIC morphology. Both the partial
      microtubule depolymerization and the inhibition of uncoating of the membranes
      result in the formation of long tubules that grow from round ERGICs and form at
      complex network. Interestingly, both COPI detachment and microtubule
      depolymerization induce a redistribution of kinesin from peripheral ERGIC
      elements to the Golgi area, while dynein distribution is not affected. However,
      both kinesin and dynein downregulation by RNA interference induced ERGIC
      tubulation. The tubules induced by kinesin depletion were static, whereas those
      resulting from dynein depletion were highly mobile. Our results strongly suggest
      that the interaction of motor proteins with COPI-coated membranes and
      microtubules is a key regulator of ERGIC morphology and mobility.

PMID- 20136778
TI  - Fluorescent detection of fluid phase endocytosis allows for in vivo estimation of
      endocytic vesicle sizes in plant cells with sub-diffraction accuracy.
AB  - Using the bright, photostable, charged and hydrophilic fluorescent dye Alexa 488
      hydrazide to label the fluid phase around intact guard cells, we show that these
      cells incorporate the fluid phase during constitutive endocytosis against the
      high turgor. Mobile, cortical and diffraction-limited signals were not observed
      if a concentration <4 mm was used to stain the fluid phase, suggesting that
      endocytic vesicles had to be loaded with a minimal number of dye molecules to
      produce a signal above the background. To quantify the number of molecules taken
      up by the vesicles, we prepared liposomes, filled with various concentrations of
      Alexa 488 hydrazide, fractionated them according to their size and imaged them
      under identical conditions as the guard cells. From the size/intensity relations
      of these liposomes, we extrapolated the molecular brightness of Alexa 488
      hydrazide. Using this calibration, the mean fluorescent intensity of single
      endocytic vesicles translates into a mean number of 573 Alexa 488 molecules. If a
      vesicle needs to take up 573 molecules from a 4 mm solution, it requires a
      diameter of at least 87 nm. This number provides the first in vivo estimate for
      the size of endocytic vesicles in intact, turgid plant cells.

PMID- 20136779
TI  - Assessment of the clinical transfusion practice at a regional referral hospital
      in Uganda.
AB  - The aim of this study was to determine the indications for transfusion, blood
      ordering practices and post-transfusion complications, and to assess the clinical
      transfusion practice at Mbarara Regional Referral Hospital (MRRH) in Mbarara,
      Uganda. There are no guidelines on the appropriate use of blood at MRRH.
      Therefore, there was a need to assess the local clinical transfusion practice.
      Patients' hospital files were studied for evidence of blood transfusions in 2008.
      All five wards were reviewed and details on the transfusion process were
      recorded. A total of 1730 patients (median age, 19.0 years; range, 1 day to 88
      years; female-to-male ratio, 1.4), for whom blood was cross-matched, were
      studied. Of these, 1674 (96.8%) patients actually received transfusions, which
      were as whole blood in 58.4% of recipients. The mean number of units per
      recipient was 1.7 and the cross-match-to-transfusion ratio was 1.3. The three
      most frequent indications for transfusion were malaria (38.8%), bleeding (27.1%)
      and other infections (16.1%). There were no records for pre-transfusion
      haemoglobin, compatibility testing, transfusion start-times and vital signs in
      30.2, 51.8, 21.5 and 97.6% of the recipients, respectively. Transfusion reactions
      were recorded for 10 (0.6%) patients. Although there was no evidence of blood
      wastage, inadequacies were noted in the documentation of the transfusion process.
      There is a need to train staff in blood transfusion and to design a 'blood
      transfusion form' for easy monitoring and evaluation. A hospital transfusion
      committee and guidelines on the appropriate use of blood should be put in place
      at MRRH.

PMID- 20136780
TI  - Immunomagnetic selection of CD34(+) cells carried out in cryopreserved cell
      concentrates from a paediatric patient affected with non-Hodgkin lymphoma.

PMID- 20136781
TI  - Stem cell collection in unmanipulated HLA-haploidentical/mismatched related
      transplantation with combined granulocyte-colony stimulating factor-mobilised
      blood and bone marrow for patients with haematologic malignancies: the impact of
      donor characteristics and procedural settings.
AB  - Unmanipulated haploidentical/mismatched related transplantation with combined
      granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G
      PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has
      been developed as an alternative transplantation strategy for patients with
      haematologic malignancies. However, little information is available about the
      factors predicting the outcome of peripheral blood stem cell (PBSC) collection
      and bone marrow (BM) harvest in this transplantation. The effects of donor
      characteristics and procedure factors on CD34(+) cell yield were investigated. A
      total of 104 related healthy donors received granulocyte-colony stimulating
      factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had
      significantly higher yields compared with female donors. In multiple regression
      analysis for peripheral blood collection, age and flow rate were negatively
      correlated with cell yield, whereas body mass index, pre-aphaeresis white blood
      cell (WBC) and circulating immature cell (CIC) counts were positively correlated
      with cell yields. For BM harvest, age was negatively correlated with cell yields,
      whereas pre-BM collection CIC counts were positively correlated with cell yield.
      All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body
      weight. This transplantation strategy has been shown to be a feasible approach
      with acceptable outcomes in stem cell collection for patients who received HLA
      haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In
      donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell
      yield, BM was an alternative source.

PMID- 20136782
TI  - Establishment of platelet donor registry improves the treatment of platelet
      transfusion refractoriness in Guangzhou region of China.
AB  - Platelet transfusion refractoriness (PTR) is the major complication of long-term
      platelet supportive care. To improve the effectiveness of platelet transfusion
      therapy in PTR patients, we aimed to establish a platelet donor registry in our
      region (Guangzhou, China) by typing the human leukocyte antigen (HLA) and human
      platelet antigen (HPA). Blood donors (n = 864) from our population were genotyped
      for HLA-A, HLA-B and HPA systems by polymerase chain reaction amplification with
      sequence-specific primer(PCR-SSP) techniques. Using this cohort, we compared the
      results of platelet transfusions (matched vs. random) in 23 patients with PTR.
      Matched platelets were selected either by HLA antigen matching or by HLA antibody
      matching, as predicted by antibody specificity prediction (ASP) analysis.
      Significantly higher platelet recovery (PPR) values were obtained with HLA
      matched platelets in comparison with random platelets. No significant difference
      in PPR was observed between HLA matching and ASP methods. In two patients,
      platelet-specific alloantibodies (alloabs) (anti-HPA-3b and anti-HPA-5b) were
      detected besides HLA class I alloabs. Transfusion with HLA- and HPA-compatible
      platelets in both the patients resulted in significantly higher PPR when compared
      with HLA-compatible platelet transfusion alone. In this study, we demonstrated
      that the establishment of an HLA- and HPA-typed platelet aphaeresis donor
      registry is useful to improve the treatment outcome of PTR patients and to
      maintain a long-term platelet transfusion strategy.

PMID- 20136783
TI  - ADP-dependent platelet function prior to and in the early course of pediatric
      liver transplantation and persisting thrombocytopenia are positively correlated
      with ischemia/reperfusion injury.
AB  - Little is known about the role of platelets in relation to ischemia/reperfusion
      injury (IRI) of the liver graft especially in children. Thrombocyte function was
      prospectively analysed in 21 consecutive pediatric liver transplantation (pLT)
      patients by platelet aggregometry secondary to adenosine diphosphate (ADP),
      collagen, and the von Willebrand factor activator ristocetin (VWF:rco). Post-OP
      serum levels of ALT were used to divide patients into groups with high (highHD, n
      = 8) and low (lowHD, n = 13) hepatocellular damage. Clinically, highHD-patients
      showed impaired plasmatic coagulation and elevated serum bilirubin levels early
      after pLT when compared with lowHD-patients. Further, platelet counts markedly
      decreased between pre-OP and postreperfusion (postrep.) in the highHD group (P =
      0.003) and did not recuperate by POD6. In lowHD individuals thrombocytopenia
      improved from both pre-OP (P < 0.05) and postrep. (P < 0.001) respectively
      towards POD6. Experimental thrombocyte testing revealed that before graft
      reperfusion only ADP-dependent platelet aggregation correlated with reperfusion
      injury, thrombocytopenia and early graft function. During the first 48 h after
      graft reperfusion, all inducers tested demonstrated elevated platelet aggregation
      levels in the highHD group. Our data suggest a possible role of platelets and
      their aggregative status in liver IRI subsequent to clinical pLT. Reperfusion
      independent ADP-triggered platelet function may be a determinant for IRI in the
      pediatric hepatic graft recipient.

PMID- 20136784
TI  - mTOR inhibition: the learning curve in kidney transplantation.
AB  - All immunosuppressive medications require a learning curve that enables
      clinicians to improve the therapeutic index of agents. Mammalian target of
      rapamycin (mTOR) inhibitors are potentially a less nephrotoxic form of
      immunosuppression than calcineurin inhibitors (CNIs) that has been used in kidney
      transplant recipients for more than two decades. This drug class has a novel
      immunosuppressive action, probably mediated in part through inhibition of growth
      receptor signaling mechanisms. In addition, it has a unique drug toxicity, which
      is partially dose-related. This medication class also possesses antiproliferative
      activity, which may be useful in-post-transplant patients with increased
      atherosclerotic and malignancy risks. mTOR inhibitors have been utilized for de
      novo immunosuppression with CNIs, corticosteroids, and antimetabolites. mTOR
      inhibitors also have been used as CNI-sparing agents both early and late post
      transplant. Much debate remains over how to best utilize mTOR inhibition in
      kidney transplantation.

PMID- 20136785
TI  - The number of circulating recent thymic emigrants is severely reduced 1 year
      after a single dose of alemtuzumab in renal transplant recipients.
AB  - To better understand the kinetics of the delayed reconstitution of peripheral
      CD4+ T-cells after depletion with a single administration of alemtuzumab (AL) for
      renal transplantation, we evaluated in these patients the percentage and absolute
      number of recent thymic emigrants (RTEs) CD4+ T cells, together with naive and
      memory subsets, defined by the analysis of CD31, CD45RA and CCR7 expression, and
      compared with patients treated with a nondepleting protocol based on basiliximab,
      and with healthy controls. In AL-treated patients, the number of circulating CD4+
      T cells was greatly reduced 1 year after the infusion (P < 0.01), but the
      proportions of central memory, effector memory and terminally differentiated
      effector memory subsets among CD4+ cells were significantly increased. On the
      contrary, the proportion and the absolute number of naive CD4+ T cells, although
      progressively increasing with time, were severely reduced. In particular, the
      absolute number of RTEs had only very slight increase with time (P = 0.049) and
      was dramatically low 1 year after the therapy (P < 0.01 vs. healthy controls; P <
      0.05 vs. basiliximab-treated transplant recipients). These data suggest that a
      prolonged defective thymic output after AL therapy in renal transplant recipients
      is one of the main causes of the persistent CD4+ T-cell lymphopenia observed in
      these patients.

PMID- 20136786
TI  - Clinical and histopathological features of pemphigus foliaceus with and without
      eosinophilic infiltrates: a retrospective evaluation of 40 dogs.
AB  - The importance of cellular infiltrates in tissues has been investigated as a
      diagnostic tool, mechanism of pathogenesis, and prognostic indicator in certain
      human diseases. Eosinophils, in particular, have a distinct role in the
      development of cutaneous lesions in human autoimmune diseases. Identification of
      an eosinophilic infiltrate can aid the diagnosis of immunobullous disease in the
      early stages of the disease process. In canine pemphigus foliaceus, eosinophils
      are present to a variable degree within lesional tissue. This study
      retrospectively evaluated 40 dogs with pemphigus foliaceus, and examined clinical
      and histologic features and final outcomes in cases with and without eosinophilic
      infiltrates. Twenty-five of 40 dogs (63%) had an eosinophilic infiltrate in
      either the pustules/crust, follicular infundibulum or dermis. There was no
      statistically significant difference in clinical distribution or appearance of
      dermatological lesions, response to treatment, or disease outcome in dogs with or
      without an eosinophilic infiltrate. However, dogs with concurrent disease were
      significantly more likely to have an eosinophilic infiltrate (P = 0.01). Dogs
      with adverse effects associated with immunosuppressive therapy were significantly
      more likely to have an eosinophilic infiltrate (P = 0.05). Fifteen of 40 dogs
      (38%) had a history of allergic disease and a significantly higher proportion of
      these dogs had an eosinophilic infiltrate (P = 0.04). An eosinophilic infiltrate
      was found in more than half of the dogs in this study. These findings justify
      further studies to investigate the role of eosinophils in the pathogenesis,
      therapy and prognosis in dogs with pemphigus foliaceus.

PMID- 20136787
TI  - Expression of claudin-5 in hepatoid gland biopsies.
AB  - Claudins are integral membrane proteins involved in the structure of the tight
      junctions found in epithelial and endothelial cells. This study evaluated the
      expression of claudin-5 in 67 hyperplastic and neoplastic lesions of canine
      hepatoid glands. These included normal hepatoid glands (n = 10), nodular
      hyperplasia (n = 10), adenomas (n = 12), epitheliomas (n = 15), differentiated
      carcinomas (n = 15) and anaplastic carcinomas (n = 15). There was intense lateral
      membrane expression of claudin-5 on epithelial cells from normal hepatoid glands,
      nodular hyperplasia and adenomas, but expression was weaker in hepatoid gland
      epitheliomas. Basal reserve cells from normal glands, nodular hyperplasia,
      adenomas and epitheliomas never expressed claudin-5. There was membrane-bound
      immunoreactivity for claudin-5 in selected areas of the epitheliomas where the
      cells exhibited typical hepatoid features. The weak expression of claudin-5
      molecule in epitheliomas may nevertheless lead to cellular disorientation,
      detachment and invasion. Claudin-5 expression seemed to be helpful in
      distinguishing poorly differentiated carcinomas, differentiated carcinomas and
      epitheliomas of the hepatoid glands. Increased claudin-5 expression by invasive
      anaplastic carcinomas may facilitate invasion and metastasis through the
      activation of matrix metalloproteinases.

PMID- 20136788
TI  - Multiple perianal infundibular follicular cysts in a dog.
AB  - This case report describes a 7-year-old male cocker spaniel dog with multiple
      perianal infundibular follicular cysts. Clinically the dog had moderate anal
      sacculitis, peri-anal pruritus causing it to 'scoot' and lick the area. On
      examination of the perianal area, there were over 100 firm, well circumscribed
      papules, ranged from 0.2 to 0.5 cm in diameter with a central pore, and were
      found in the perianal region. Alopecia was present in the perianal region. The
      skin tissue in the perianal region resected surgically was submitted for
      histological examination. Microscopically, the tissue revealed multiple dilated
      cysts filled with keratins and the papules corresponded to infundibular
      follicular cysts. The affected dog showed moderate anal sacculitis. Anal
      sacculitis commonly causes repeated scooting or licking the area around the anus.
      Therefore, the multiple follicular cysts in the present case appear to be
      primarily a sequela to chronic external trauma to the perianal area, probably in
      response to anal sacculitis. To the best of the authors' knowledge, the present
      report is the first documented case of multiple perianal infundibular follicular
      cysts in a dog.

PMID- 20136791
TI  - Red blood cell transfusions in the postpartum patient.

PMID- 20136789
TI  - The use of malaria antibody tests in the prevention of transfusion-transmitted
      malaria.

PMID- 20136792
TI  - A new RHD-positive, D antigen negative allele in Chinese.

PMID- 20136793
TI  - Hepatitis E virus and blood donors in Germany.

PMID- 20136794
TI  - Changes in presumed motor cortical activity during fatiguing muscle contraction
      in humans.
AB  - AIM: Changes in sensory information from active muscles accompany fatiguing
      exercise and the force-generating capacity deteriorates. The central motor
      commands therefore must adjust depending on the task performed. Muscle potentials
      evoked by transcranial magnetic stimulation (TMS) change during the course of
      fatiguing muscle activity, which demonstrates activity changes in cortical or
      spinal networks during fatiguing exercise. Here, we investigate cortical
      mechanisms that are actively involved in driving the contracting muscles.
      METHODS: During a sustained submaximal contraction (30% of maximal voluntary
      contraction) of the elbow flexor muscles we applied TMS over the motor cortex. At
      an intensity below motor threshold, TMS reduced the ongoing muscle activity in
      biceps brachii. This reduction appears as a suppression at short latency of the
      stimulus-triggered average of rectified electromyographic (EMG) activity. The
      magnitude of the suppression was evaluated relative to the mean EMG activity
      during the 50 ms prior to the cortical stimulus. RESULTS: During the first 2 min
      of the fatiguing muscle contraction the suppression was 10 +/- 0.9% of the
      ongoing EMG activity. At 2 min prior to task failure the suppression had reached
      16 +/- 2.1%. In control experiments without fatigue we did not find a similar
      increase in suppression with increasing levels of ongoing EMG activity.
      CONCLUSION: Using a form of TMS which reduces cortical output to motor neurones
      (and disfacilitates them), this study suggests that neuromuscular fatigue
      increases this disfacilitatory effect. This finding is consistent with an
      increase in the excitability of inhibitory circuits controlling corticospinal
      output.

PMID- 20136795
TI  - TRAF6 knockdown promotes survival and inhibits inflammatory response to
      lipopolysaccharides in rat primary renal proximal tubule cells.
AB  - AIM: TRAF6 is a unique adaptor protein of the tumour necrosis factor receptor
      associated factor family that mediates both tumour necrosis factor receptor
      (TNFR) and interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signalling.
      Activation of IL-1R/TLR and TNFR pathways in renal tubular cells contributes to
      renal injury. This study aimed to investigate if blockade of lipopolysaccharide
      (LPS)-triggered TLR4 signalling by small interfering RNA (siRNA) targeting TRAF6
      protects survival and inhibits inflammatory response in isolated rat renal
      proximal tubular cells (PTCs). METHODS: PTCs isolated from F344 rat kidneys were
      transfected with chemically synthesized siRNA targeting TRAF6 mRNA. Real-time
      quantitative PCR was applied to measure mRNA level of TRAF6, TNF-alpha, IL-6 and
      monocyte chemoattractant protein-1 (MCP-1). Protein levels of extracellular
      signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), p38 mitogen
      activated protein kinase, caspase 3 and cleaved caspase 3 were evaluated by
      Western blotting. Cell viability was analysed with XTT reagents. RESULTS: We
      found that the TRAF6 gene was effectively silenced in PTCs using siRNA. TRAF6
      knockdown resulted in reduced TNF-alpha and IL-6 mRNA expression upon LPS
      challenge. LPS-induced phosphorylation of JNK and p38 was attenuated in TRAF6
      siRNA-transfected cells while the change in the phosphorylation of ERK was not
      remarkable. TRAF6 knockdown was associated with increased cell viability and
      reduced protein level of cleaved caspase-3, both, in the absence and presence of
      LPS. CONCLUSION: Our studies suggest that TRAF6 knockdown may inhibit
      inflammatory response and promote cell survival upon LPS challenge in primary rat
      proximal renal tubular cells.

PMID- 20136796
TI  - Prostaglandin I(2) sensory input into the enteric nervous system during
      distension-induced colonic chloride secretion in rat colon.
AB  - AIM: Intestinal pressure differences or experimental distension induce ion
      secretion via the enteric nervous system, the sensorial origin of which is only
      poorly understood. This study aimed to investigate sensorial inputs and the role
      of afferent and interneurones in mechanically activated submucosal secretory
      reflex circuits. METHODS: Distension-induced rheogenic chloride secretion was
      measured as increase in short-circuit current 10 min after distension
      (DeltaI(SC)(10); distension parameters +/- 100 microL, 2 Hz, 20 s) in partially
      stripped rat distal colon in the Ussing-chamber in vitro. PGE(2) and PGI(2) were
      measured by radioimmunoassay. RESULTS: DeltaI(SC)(10) was 2.0 +/- 0.2 micromol h(
      1) cm(-2) and could be attenuated by lobeline, mecamylamine and
      dimethylphenylpiperazine, indicating an influence of nicotinergic interneurones.
      Additionally, a contribution of afferent neurones was indicated from the short
      term potentiation of DeltaI(SC)(10) by capsaicin (1 microm). As evidence for its
      initial event, indomethacin (1 microm) inhibited distension-induced secretion and
      the release of PGI(2) was directly detected after distension. Furthermore,
      serotoninergic mediation was confirmed by granisetron (100 microm) which was
      functionally localized distally to PGI(2) in this reflex circuit, as granisetron
      inhibited an iloprost-induced I(SC), while indomethacin did not affect serotonin
      activated ion secretion. CONCLUSIONS: Distension-induced active electrogenic
      chloride secretion in rat colon is mediated by a neuronal reflex circuit which
      includes afferent neurones and nicotinergic interneurones. It is initiated by
      distension-induced PGI(2) release from subepithelial cells triggering this reflex
      via serotoninergic 5-HT(3) receptor transmission. Functionally, this mechanism
      may help to protect against intestinal stasis but could also contribute to
      luminal fluid loss, e.g. during intestinal obstruction.

PMID- 20136797
TI  - Changes in expression and activity levels of ecto-5'-nucleotidase/CD73 along the
      mouse female estrous cycle.
AB  - AIM: Extracellular ATP and its hydrolysis product adenosine modulate various
      reproductive functions such as those requiring contraction, hormone synthesis and
      maintenance of fluid composition. Moreover, adenosine is a key molecule for sperm
      capacitation. Extracellular nucleotide and nucleoside levels are affected by cell
      surface ectonucleotidases, amongst which the ectonucleoside triphosphate
      diphosphohydrolase (E-NTPDase) family is the most abundant and effective to
      hydrolyse ATP and ADP to AMP. In the female reproductive tract three members of
      this family have been recently identified: NTPDase1, NTPDase2 and NTPDase3
      (Histochem. Cell Biol.131, 2009, 615). The purpose of the present study was to
      characterize in this system the expression profile of ecto-5'-nucleotidase
      (CD73), the enzyme generating adenosine from AMP. METHODS: Immunological
      techniques and in situ enzymatic assays were used to characterize the ecto-5'
      nucleotidase expression in the mouse female reproductive tract along the four
      stages of the estrous cycle, that were determined by vaginal smear examination.
      RESULTS: Ecto-5'-nucleotidase was abundantly detected in the corpora lutea of the
      ovaries, as well as in several epithelia, such as that of oviducts, uterus and
      endometrial glands. Marked changes in endometrial ecto-5'-nucleotidase expression
      and activity along the estrous cycle are described, these being maximum at estrus
      phase, coinciding with optimal female sexual receptivity. CONCLUSION: The
      adenosine generated thereby, besides other functions, might contribute to sperm
      capacitation, thus significantly influencing fertility.

PMID- 20136798
TI  - Sedoanalgesia in paediatric intensive care: a survey of 19 Italian units.
AB  - AIM: To analyse the methods used to manage and monitor sedoanalgesia at Italian
      paediatric intensive care units (ICUs). METHODS: Data were collected by
      administering a questionnaire that aimed to investigate whether ICUs adopted a
      validated protocol to manage sedoanalgesia. RESULTS: The results revealed that a
      majority of the ICUs adopt a protocol for dealing with sedation and analgesia,
      but this protocol is implemented with difficulty or not at all in routine
      clinical practice. The most often used pharmacological combination, is midazolam
      and fentanyl. Several weaknesses remain in terms of the methods used to assess
      sedoanalgesia, which are generally not standardized, but rather based on
      recording the patient's physiological parameters. CONCLUSION: Sedation and
      analgesia are priority issues in the management of critically ill children. None
      of the numerous drugs available is ideal and the protocols currently used in
      clinical practice involve the combined use of different drugs. There is currently
      no shared and validated approach as to which is the most effective and safest
      sedoanalgesic regimen in critically ill children.

PMID- 20136799
TI  - Iatrogenic risks--something we should always be mindful of.

PMID- 20136800
TI  - Cancer risk from diagnostic radiology in a deliberate self-harm patient.
AB  - OBJECTIVE: Patients who engage in recurrent deliberate self-harm (DSH) behaviours
      have increased morbidity and mortality and use emergency services more than
      others. Unrecognized iatrogenic injury may play a role. Specifically, we call
      attention to the potential danger of cumulative radiation exposure. METHOD: Case
      presentation and discussion. RESULTS: A 29-year-old woman with multiple episodes
      of deliberate foreign body ingestion received over 400 diagnostic radiology
      examinations during a 12 year period. The patient's calculated total radiation
      dose reached an average of 20.5 mSv per year, a dose comparable to atomic bomb
      survivors and nuclear industry workers, populations in which there is a
      significant excess cancer risk. CONCLUSION: Patients with recurrent self
      injurious behaviours, frequent users of healthcare services who often undergo
      repeated medical assessment and treatment, are likely at higher risk for
      iatrogenic adverse events. Multiple diagnostic radiology examinations have
      recently come under scrutiny for causing increased lifetime risk of cancer.
      Healthcare providers, in particular psychiatrists and emergency department
      physicians, should consider the cumulative risks of radiological procedures when
      assessing and treating patients with DSH.

PMID- 20136801
TI  - Efficacy and safety of two treatment algorithms in bipolar depression consisting
      of a combination of lithium, lamotrigine or placebo and paroxetine.
AB  - OBJECTIVE: In a previous paper, we reported about the efficacy of the addition of
      lamotrigine to lithium in patients with bipolar depression. In the second phase
      of this study paroxetine was added to ongoing treatment in non-responders.
      METHOD: Bipolar depressed patients (n = 124) treated with lithium were randomized
      to addition of lamotrigine or placebo. In non-responders after 8 weeks,
      paroxetine 20 mg was added for another 8 weeks to ongoing treatment. RESULTS:
      After 8 weeks the improvement in patients treated with lamotrigine vs. patients
      treated with placebo was significant. After addition of paroxetine this
      difference disappeared as a result of greater further improvement in the non
      responders to placebo. CONCLUSION: Addition of lamotrigine to lithium was found
      effective in bipolar depressed patients. Further addition of paroxetine in non
      responders to lithium plus lamotrigine did not appear to provide additional
      benefit, while it appeared to do so in non-responders to lithium plus placebo.

PMID- 20136802
TI  - Predictors of the recurrence of hepatic encephalopathy in lactulose-treated
      patients.
AB  - BACKGROUND: Lactulose is considered first-line therapy for hepatic
      encephalopathy. However, the effect of adherence with lactulose on recurrence of
      hepatic encephalopathy outside clinical trials remains unclear. AIM: To determine
      the association of lactulose use with recurrence of hepatic encephalopathy
      episodes. METHODS: Patients with cirrhosis who were initiated on lactulose after
      an index hepatic encephalopathy episode in a liver-transplant centre were
      retrospectively reviewed. Recurrence of hepatic encephalopathy, precipitating
      factors and adherence on lactulose were investigated using chart review and
      electronic pharmacy records. Patients with/without hepatic encephalopathy
      recurrence were compared, and predictors of recurrence were analysed. RESULTS: A
      total of 137 patients with cirrhosis (age 55 +/- 6years, MELD 17 +/- 7) who were
      initiated on lactulose after the index hepatic encephalopathy episode were
      included. Of these, 103 patients developed recurrent hepatic encephalopathy 9 +/-
      1 months after their index episode; 39 (38%) of these were not adherent on
      lactulose, 56 (54%) were adherent and 8 (8%) had lactulose-associated dehydration
      leading to recurrence. Recurrent hepatic encephalopathy precipitants in lactulose
      adherent patients were sepsis (19%), GI bleeding (15%), hyponatremia (4%) and
      TIPS (7%). Overall, all patients who did not suffer recurrence were adherent on
      lactulose. In contrast, the adherence rate for those who recurred was only 64% (P
      = 0.00001). On multivariate regression, lactulose non-adherence (OR 3.26) and
      MELD score (OR 1.14) were the factors that predicted recurrence. CONCLUSION:
      Lactulose non-adherence and lactulose-associated dehydration were associated with
      nearly half of recurrent hepatic encephalopathy episodes.

PMID- 20136803
TI  - Clinical trial: interferential electric stimulation in functional dyspepsia
      patients - a prospective randomized study.
AB  - BACKGROUND: There are several studies reporting the beneficial effects of
      transcutaneous electrical stimulation in patients with gastroparesis and chronic
      constipation. AIM: To analyse whether transcutaneous electrical stimulation is an
      effective procedure in functional dyspepsia patients. METHODS: Functional
      dyspepsia patients were randomly placed in vacuum interferential current (IFC)
      and placebo groups. Both treatments consisted of 12 sessions administered over 4
      weeks. Upper gastrointestinal system symptoms were documented at the beginning,
      during and after the treatment sessions. RESULTS: Patients in therapy (23 cases)
      and placebo (21 cases) groups were homogeneous with respect to demographic data
      and upper gastrointestinal system symptoms. In the therapy group, all symptoms
      other than early satiation improved significantly during and after the treatment
      sessions, whereas in the placebo group, symptoms including heartburn and vomiting
      did not change significantly. IFC therapy was superior to placebo with respect to
      epigastric discomfort, pyrosis, bloating, early satiation and postprandial
      fullness during the treatment sessions. One month after the treatment sessions,
      vacuum IFC proved to be superior to placebo with regard to early satiation and
      heartburn. CONCLUSIONS: Vacuum IFC is a non-invasive and effective therapy for
      functional dyspepsia. Transcutaneous electrical stimulation may represent a new
      treatment modality for drug-refractory functional dyspepsia patients.

PMID- 20136804
TI  - Modification of Tp-e and QTc intervals during caesarean section under spinal
      anaesthesia.
AB  - There are no guidelines for the anaesthetic management of caesarean section in
      women with long QT syndrome; the description of myocardial ventricular
      repolarisation in healthy women during caesarean delivery could be a first step.
      The aim of this study was to describe modification of the QT interval, corrected
      for heart rate, and the interval between the peak and the end of the T-wave
      (Tpeak-Tend interval) during caesarean section under spinal anaesthesia. We
      studied 40 patients scheduled for caesarean section under spinal anaesthesia.
      Patients were randomly assigned to receive either ephedrine or phenylephrine to
      prevent hypotension. We injected 5 IU oxytocin after delivery. Corrected QT and
      Tpeak-Tend intervals were unchanged from pre-operative values after induction of
      spinal anaesthesia, but increased significantly after oxytocin injection. The
      choice of vasopressor did not affect the Tpeak-Tend interval. The risk-benefit
      balance of oxytocin bolus during caesarean delivery should be discussed with
      women with a history of long QT syndrome.

PMID- 20136805
TI  - Anaesthetics and postoperative cognitive dysfunction: a pathological mechanism
      mimicking Alzheimer's disease.
AB  - With longevity, postoperative cognitive decline in the elderly has emerged as a
      major health concern for which several factors have been implicated, one of the
      most recent being the role of anaesthetics. Interactions of anaesthetic agents
      and different targets have been studied at the molecular, cellular and structural
      anatomical levels. Recent in vitro nuclear magnetic resonance spectroscopy
      studies have shown that several anaesthetics act on the oligomerisation of
      amyloid beta peptide. Uncontrolled production, oligomerisation and deposition of
      amyloid beta peptide, with subsequent development of amyloid plaques, are
      fundamental steps in the generation of Alzheimer's disease. Amyloid beta peptide
      is naturally present in the central nervous system, and is found at higher tissue
      concentrations in the elderly. We argue that administering certain general
      anaesthetics to elderly patients may worsen amyloid beta peptide oligomerisation
      and deposition and thus increase the risk of developing postoperative cognitive
      dysfunction. The aim of this review is to highlight the clinical aspects of
      postoperative cognitive dysfunction and to find plausible links between possible
      anaesthetic effects and the molecular pathological mechanism of Alzheimer's
      disease. It is hoped that our hypothesis will stimulate further enquiry,
      especially triggering research into elucidating those anaesthetics that may be
      more suitable when cognitive dysfunction is a particular concern.

PMID- 20136806
TI  - Colorectal cancer screening and rural Australian communities.

PMID- 20136807
TI  - Determinants of mental health and well-being in rural communities: do we
      understand enough to influence planning and policy?

PMID- 20136808
TI  - Ethics and trauma: lessons from media coverage of Black Saturday.

PMID- 20136809
TI  - Exploratory study examining barriers to participation in colorectal cancer
      screening.
AB  - OBJECTIVE: To examine the Stage of Change distribution for bowel cancer screening
      in a regional Australian community and the factors associated with varying
      positions on the continuum of change. DESIGN: Survey of a convenience sample.
      SETTING: Community sample. PARTICIPANTS: A total of 59 (31 male, mean age = 59)
      service club members from a South Australian regional community. MAIN OUTCOME
      MEASURE: Self-reported Stage of Change for bowel cancer screening behaviour.
      RESULTS: Attributing greater embarrassment and discomfort to bowel cancer
      screening was associated with earlier positions on the Stages of Change.
      Perceiving that bowel cancer screening might have positive value for personal
      health was associated with more advanced positions on the continuum of change.
      Those who perceived breast and prostate screening procedures to be embarrassing
      or to cause discomfort were significantly less likely to be participating in
      bowel cancer screening. No significant relationships were found between bowel
      cancer screening Stage of Change and worry about vulnerability; personal, family
      or wider social network case reports of bowel cancer; and the population-level
      value attributed to the cancer screening procedures. CONCLUSION: Bowel cancer
      screening participation rates are currently lower than those associated with
      breast and prostate screening. Reducing perceptions of embarrassment and
      discomfort, increasing awareness of potential health benefits and maximising
      participation in other screening procedures might increase participation in bowel
      cancer screening.

PMID- 20136810
TI  - Mental health and well-being within rural communities: the Australian rural
      mental health study.
AB  - OBJECTIVE: This paper outlines the methods and baseline data from a multisite
      cohort study of the determinants and outcomes of mental health and well-being
      within rural and remote communities. METHODS: A stratified random sample of
      adults was drawn in non-metropolitan New South Wales using the Australian
      Electoral Roll, with the aim of recruiting all adult members of each household.
      Surveys assessed psychological symptoms, physical health and mental disorders,
      along with individual-, family/household- and community-level characteristics. A
      stratified subsample completed a telephone-administered World Mental Health
      Composite International Diagnostic Interview (World Mental Health-3.0). Proxy
      measures of child health and well-being were obtained. Follow up of this sample
      will be undertaken at one, three and five years. RESULTS: A total of 2639
      individuals were recruited (1879 households), with 28% from remote/very remote
      regions. A significant relationship was found between recent distress (Kessler-10
      scores), age and remoteness, with a linear reduction of Kessler-10 scores with
      age and the lowest mean scores in remote regions. CONCLUSIONS: Existing rurality
      categories cannot address the diverse socio-cultural, economic and environmental
      characteristics of non-metropolitan regions. While it has limitations, the
      dataset will enable a fine-grained examination of geographic, household and
      community factors and provide a unique longitudinal dataset over a five-year
      period.

PMID- 20136811
TI  - Distress among rural residents: does employment and occupation make a difference?
AB  - OBJECTIVE: This study investigates the relationship between levels of mental
      health and well-being (in terms of self-reported levels of distress) with
      employment and occupational status of rural residents, to better inform the
      provision of mental health services to those in greatest need in rural
      communities. METHOD: A stratified random sample of community residents in rural
      and remote New South Wales with over-sampling of remote areas as first stage of a
      cohort study. Psychological distress was measured using Kessler-10, inclusive of
      additional items addressing functional impairment (days out of role).
      Occupational data were classified using Australian and New Zealand Standard
      Classification of Occupations categories. RESULTS: A total of 2639 adults
      participated in this baseline phase. Among them, 57% were in paid employment, 30%
      had retired from the workforce, 6% were permanently unable to work and 2% were
      unemployed. The highest levels of distress and functional impairment were
      reported in those permanently unable to work and the unemployed group with rates
      of 'caseness' (likely mental health disorder) varying from 57% to 69%, compared
      with 34% of farmers and farm managers and 29% of health workers (P < 0.01).
      CONCLUSION: The rural unemployed suffer considerable psychological distress and
      'disability', yet they are not the target of specific mental health promotion and
      prevention programs, which are often occasioned by rural adversity, such as
      drought, and delivered through work-based pathways. Policy-makers and health
      service providers need to consider the needs of the rural unemployed and those
      permanently unable to work and how they might be addressed.

PMID- 20136812
TI  - Mental health impact for adolescents living with prolonged drought.
AB  - BACKGROUND: A 2004 study showed adolescents living in rural Australia were aware
      of the impact of drought on self, family and community, but did not report levels
      of emotional distress higher than adolescents of similar age and gender in the
      Australian community. It was proposed that the rural lifestyle had helped
      adolescents build resilience for managing this environmental adversity.
      OBJECTIVE: To re sample adolescents from the same rural area and determine if
      this resilience remained after ongoing drought three years later. DESIGN: A mixed
      methods approach using focus groups and a self-report questionnaire. SETTING:
      Government Central Schools within the Riverina region of New South Wales.
      PARTICIPANTS: Male and female adolescents (n = 111) aged 11-17 years completed
      the self-report questionnaires, while some adolescents (n = 61) within this group
      also participated in focus groups. MAIN OUTCOME MEASURE: The Strengths and
      Difficulties Questionnaire and a Drought and Community Survey for Children
      comprised the self-report survey. RESULTS: Adolescents reported significantly
      higher levels of emotional distress than those in the previous study (t (191) =
      2.80, P < 0.01) and 12% of adolescents scored in the clinical caseness range.
      Thematic analysis showed consistency with the previous study as well as new
      themes of grief, loss and the impacts of global climate change. CONCLUSIONS:
      Results indicate a reporting of lesser well-being than was reported by a
      comparable group of young people four years earlier. A preventative intervention
      with a focus on family and community is recommended to address the mental health
      of adolescents enduring a chronic environmental adversity such as drought.

PMID- 20136813
TI  - Synergy and sustainability in rural procedural medicine: views from the coalface.
AB  - OBJECTIVE: The practice of rural and remote medicine in Australia entails many
      challenges, including a broad casemix and the remoteness of specialist support.
      Many rural practitioners employ advanced procedural skills in anaesthetics,
      surgery, obstetrics and emergency medicine, but the use of these skills has been
      declining over the last 20 years. This study explored the perceptions of rural
      general practitioners (GPs) on the current and future situation of procedural
      medicine. DESIGN: The qualitative results of data from a mixed-method design are
      reported. Free-response survey comments and semistructured interview transcripts
      were analysed by a framework analysis for major themes. SETTING: General
      practices in rural and remote Queensland. PARTICIPANTS: Rural GPs in Rural and
      Remote Metropolitan Classification 4-7 areas of Queensland. MAIN OUTCOME MEASURE:
      The perceptions of rural GPs on the current and future situation of rural
      procedural medicine. RESULTS: Major concerns from the survey focused on closure
      of facilities and downgrading of services, cost and time to keep up skills,
      increasing litigation issues and changing attitudes of the public. Interviews
      designed to draw out solutions to help rectify the perceived circumstances
      highlighted two major themes: 'synergy' between the support from medical teams
      and community in ensuring 'sustainability' of services. CONCLUSIONS: This article
      presents a model of rural procedural practice where synergy between staff,
      resources and support networks represents the optimal way to deliver a non
      metropolitan procedural service. The findings serve to remind educators and
      policy-makers that future planning for sustainability of rural procedural
      services must be broad-based and comprehensive.

PMID- 20136814
TI  - Greater Green Triangle Diabetes Prevention Program: remaining treatment gaps in
      hypertension and dyslipidaemia.

PMID- 20136815
TI  - A child-eating nutritionist?

PMID- 20136817
TI  - Advance directives from a cross-cultural perspective.

PMID- 20136818
TI  - End-of-life care in the 21st century: advance directives in universal rights
      discourse.
AB  - This article explores universal normative bases that could help to shape a
      workable legal construct that would facilitate a global use of advance
      directives. Although I believe that advance directives are of universal
      character, my primary aim in approaching this issue is to remain realistic. I
      will make three claims. First, I will argue that the principles of autonomy,
      dignity and informed consent, embodied in the Oviedo Convention and the UNESCO
      Declaration on Bioethics and Human Rights, could arguably be regarded as
      universal bases for the global use of advance directives. Second, I will
      demonstrate that, despite the apparent consensus of ethical authorities in
      support of their global use, it is unlikely, for the time being, that such
      consensus could lead to unqualified legal recognition of advance directives,
      because of different understandings of the nature of the international rules,
      meanings of autonomy and dignity which are context-specific and culture-specific,
      and existing imperfections that make advance directives either unworkable or
      hardly applicable in practice. The third claim suggests that the fact that the
      concept of the advance directive is not universally shared does not mean that it
      should not become so, but never as the only option in managing incompetent
      patients. A way to proceed is to prioritize work on developing higher standards
      in managing incompetent patients and on progressing towards the realization of
      universal human rights in the sphere of bioethics, by advocating a universal,
      legally binding international convention that would outlaw human rights
      violations in end-of-life decision-making.

PMID- 20136819
TI  - A Korean perspective on developing a global policy for advance directives.
AB  - Despite the wide and daunting array of cross-cultural obstacles that the
      formulation of a global policy on advance directives will clearly pose, the need
      is equally evident. Specifically, the expansion of medical services driven by
      medical tourism, just to name one important example, makes this issue urgently
      relevant. While ensuring consistency across national borders, a global policy
      will have the additional and perhaps even more important effect of increasing the
      use of advance directives in clinical settings and enhancing their effectiveness
      within each country, regardless of where that country's state of the law
      currently stands. One cross-cultural issue that may represent a major obstacle in
      formulating, let alone applying, a global policy is whether patient autonomy as
      the underlying principle for the use of advance directives is a universal norm or
      a construct of western traditions that must be reconciled with alternative value
      systems that may place lesser significance on individual choice. A global policy,
      at a minimum, must emphasize respect for patient autonomy, provision of medical
      information, limits to the obligations for physicians, and portability. And
      though the development of a global policy will be no easy task, active engagement
      in close collaboration with the World Health Organization can make it possible.

PMID- 20136820
TI  - Advance directives in the Netherlands: an empirical contribution to the
      exploration of a cross-cultural perspective on advance directives.
AB  - RESEARCH OBJECTIVE: This study focuses on ADs in the Netherlands and introduces a
      cross-cultural perspective by comparing it with other countries. METHODS: A
      questionnaire was sent to a panel comprising 1621 people representative of the
      Dutch population. The response was 86%. RESULTS: 95% of the respondents didn't
      have an AD, and 24% of these were not familiar with the idea of drawing up an AD.
      Most of those familiar with ADs knew about the Advanced Euthanasia Directive
      (AED, 64%). Both low education and the presence of a religious conviction that
      plays an important role in one's life increase the chance of not wanting to draw
      up an AD. Also not having experienced a request for euthanasia from someone else,
      and the inconceivability of asking for euthanasia yourself, increase the chance
      of not wanting to draw up an AD. DISCUSSION: This study shows that the subjects
      of palliative care and end-of-life-decision-making were very much dominated by
      the issue of euthanasia in the Netherlands. The AED was the best known AD; and
      factors that can be linked to euthanasia play an important role in whether or not
      people choose to draw up an AD. This differentiates the Netherlands from other
      countries and, when it comes to ADs, the global differences between countries and
      cultures are still so large that the highest possible goals, at this moment in
      time, are observing and possibly learning from other cultural settings.

PMID- 20136821
TI  - Advance directives in Turkey's cultural context: examining the potential benefits
      for the implementation of patient rights.
AB  - Advance directives are not a part of the healthcare service in Turkey. This may
      be related with the fact that paternalism is common among the healthcare
      professionals in the country, and patients are not yet integrated in the decision
      making process adequately. However, starting from the enactment of the Regulation
      of Patient Rights in 1998, this situation started to change. While the
      paternalist tradition still appears to be strong in Turkey, the Ministry of
      Health has been taking concrete measures in the recent years to ensure that
      patient rights are implemented in healthcare practice. Therefore, Turkey now
      seems to be in a transitional period where a move towards a more patient-autonomy
      centred approach is being supported by the regulatory authorities, as well as the
      academic circles and the public at large. In the light of this background, this
      paper aims to examine the potential benefits of advance directives, particularly
      with regard to their possible effect in the clinical decision-making process of
      Turkey's context. It will be argued that advance directives, if correctly
      understood and implemented in the right settings, may be beneficial, particularly
      for improving communication between patients and healthcare professionals and for
      implementing of the right to refuse treatment.

PMID- 20136822
TI  - Reclaiming the patient's voice and spirit in dying: an insight from Israel.
AB  - In the latter half of the 20th century, Western medicine moved death from the
      home to the hospital. As a result, the process of dying seems to have lost its
      spiritual dimension, and become a matter of prolonging material life by means of
      medical technology. The novel quandaries that arose led in turn to medico-legal
      regulation. This paper describes the recent regulation of dying in Israel under
      its Dying Patient Law, 2005. The Law recognizes advance directives in principle,
      but limits their effect and form through complex medico-legal artifices. It
      reflects a culture that places high value on both scientific medicine and the
      sanctity of life as such, and illustrates a medical culture that pitches battle
      against death. At the same time, the Law constructs the will of the individual in
      a medico-legal language that is alien to the lay person. The paper suggests an
      alternative approach to advance care planning that is patient-centred and
      addresses the psycho-social needs of the individual in terms of her relational
      autonomy. From this perspective, advance care planning becomes an opportunity to
      extract the patient from the medical context and allow her to speak about her
      approaching death with close ones in her own terms of reference. To this end,
      there is a need for facilitation of an intimate encounter where patients can
      speak about their concerns with their loved ones. The paper also presents a
      methodological approach of attentive listening, which can be applied across
      diverse cultures and circumstances.

PMID- 20136823
TI  - 'Vague Oviedo': autonomy, culture and the case of previously competent patients.
AB  - The paper examines the ethical and legal challenges of making decisions for
      previously competent patients and the role of advance directives and legal
      representatives in light of the Oviedo Convention. The paper identifies gaps in
      the Convention that result in conflicting instructions in cases of a disagreement
      between the expressed prior wishes of a patient, and the legal representative.
      The authors also examine the legal and moral status of informally expressed prior
      wishes of patients unable to consent. The authors argue that positivist legal
      reasoning is insufficient for a consistent interpretation of the relevant
      provisions of the Convention and argue that ethical argumentation is needed to
      provide guidance in such cases. Based on the ethical arguments, the authors
      propose a way of reconciling the apparent inconsistencies in the Oviedo
      Convention. They advance a culturally sensitive approach to the application of
      the Convention at the national level. This approach understands autonomy as a
      broader, relational consent and emphasizes the social and cultural embeddedness
      of the individual. Based on their approach, the authors argue that there exists a
      moral obligation to respect the prior wishes of the patient even in countries
      without advance directives. Yet it should be left to the national legislations to
      determine the extent of this obligation and its concrete forms.

PMID- 20136824
TI  - Increased adhesive properties of platelets in sickle cell disease: roles for
      alphaIIb beta3-mediated ligand binding, diminished cAMP signalling and increased
      phosphodiesterase 3A activity.
AB  - Whilst high pro-coagulant activity is reported in sickle cell disease (SCD), the
      precise role of platelets (PLTs) in SCD inflammatory and vaso-occlusive processes
      is unclear. Adhesion of PLTs from healthy controls (CON), SCD individuals (SCD)
      and SCD patients on hydroxycarbamide (SCDHC) to fibrinogen (FB) was compared
      using static adhesion assays. PLT adhesion molecules and intraplatelet cyclic
      adenosine monophosphate (icAMP) were observed by flow cytometry and enzyme-linked
      immunosorbent assay. SCD-PLTs demonstrated significantly greater adhesion than
      CON-PLTs to FB. Participation of the alpha(IIb)beta(3)-integrin in SCD-PLT
      adhesion was implicated by increased alpha(IIb)beta(3) activation and data
      showing that an alpha(IIb)beta(3)-function-inhibiting antibody significantly
      diminished SCD-PLT adhesion to FB. Platelet activation was potentiated by
      reductions in icAMP; cAMP levels were decreased in SCD-PLTs, being comparable to
      those of thrombin-stimulated CON-PLTs. Furthermore, SCD-PLT adhesion to FB was
      significantly reduced by cilostazol, an inhibitor of cAMP-hydrolyzing
      phosphodiesterase 3A (PDE3A). Both alpha(IIb)beta(3)-integrin activation and
      icAMP correlated significantly with fetal haemoglobin in SCD. Accordingly,
      hydroxycarbamide therapy was associated with lower PLT adhesion and higher icAMP.
      SCD-PLTs may be capable of adhering to proteins encountered on the inflamed
      vascular wall and, potentially, participate in vaso-occlusive processes.
      Hydroxycarbamide and, speculatively, nitric oxide donor or cyclic-nucleotide
      targeted therapies may aid in the reversal of PLT adhesive properties in SCD.

PMID- 20136825
TI  - Prolonged survival with improved tolerability in higher-risk myelodysplastic
      syndromes: azacitidine compared with low dose ara-C.
AB  - In the phase III AZA-001 trial, low-dose cytarabine (LDara-C), the most widely
      used low-dose chemotherapy in patients with higher-risk myelodysplastic syndrome
      (MDS) who are ineligible for intensive treatment, was found to be associated with
      poorer survival compared with azacitidine. This analysis further compared the
      efficacy and the toxicity of these two drug regimens. Before randomization,
      investigators preselected patients to receive a conventional care regimen, one of
      which was LDara-C. Of 94 patients preselected to LDara-C, 45 were randomized to
      azacitidine and 49 to LDara-C. Azacitidine patients had significantly more and
      longer haematological responses and increased red blood cell transfusion
      independence. Azacitidine prolonged overall survival versus LDara-C in patients
      with poor cytogenetic risk, presence of -7/del(7q), and French-American-British
      subtypes refractory anaemia with excess blasts (RAEB) and RAEB in transformation.
      When analyzed per patient year of drug exposure, azacitidine treatment was
      associated with fewer grade 3-4 cytopenias and shorter hospitalisation time than
      LDara-C in these higher-risk MDS patients.

PMID- 20136826
TI  - Haematopoeitic cell transplantation for Fanconi anaemia - when and how?
AB  - Allogeneic haematopoietic cell transplantation (HCT) remains the only treatment
      that can correct the haematological manifestations in patients with Fanconi
      anaemia. Over the last two decades, sequential changes to the approach to HCT
      have resulted in reduced regimen-related toxicity, superior engraftment and less
      graft-versus-host disease (GVHD), resulting in improved survival. The two pivotal
      changes that most influenced these improvements were the addition of fludarabine
      to the preparative regimen to augment engraftment, and the use of T cell
      depletion to reduce GVHD. With these improved HCT outcomes, indications for HCT
      are quite consistent regardless of donor source. Emphasis is now being placed on
      developing HCT regimens that will improve quality of life by reducing late
      effects, particularly the risk of malignancy, sterility and endocrinopathies.
      This paper will review the unique challenges of HCT in FA patients, with
      particular emphasis on the timing and approach to HCT.

PMID- 20136827
TI  - Poly(lactic acid-glycolic acid) nanoparticles markedly improve immunological
      protection provided by peptide P10 against murine paracoccidioidomycosis.
AB  - BACKGROUND AND PURPOSE: The present study reports on the preparation and testing
      of a sustained delivery system for the immunomodulatory peptide P10 aimed at
      reducing the in vivo degradation of the peptide and the amount required to elicit
      a protective immune response against paracoccidioidomycosis. EXPERIMENTAL
      APPROACH: BALB/c mice were infected with the yeast Paracoccidioides brasiliensis
      to mimic the chronic form of paracoccidioidomycosis. The animals were treated
      daily with sulfamethoxazole/trimethoprim alone or combined with peptide P10,
      either emulsified in Freund's adjuvant or entrapped in poly(lactic acid-glycolic
      acid) (PLGA) nanoparticles at different concentrations (1 microg, 5 microg, 10
      microg, 20 microg or 40 microg.50 microL(-1)). Therapeutic efficacy was assessed
      as fungal burden in tissues and the immune response by quantitative determination
      of cytokines. KEY RESULTS: Animals given combined chemotherapy and P10
      nanotherapy presented a marked reduction of fungal load in the lungs, compared
      with the non-treated animals. After 30 days of treatment, P10 entrapped within
      PLGA (1 microg.50 microL(-1)) was more effective than 'free' P10 emulsified in
      Freund's adjuvant (20 microg.50 microL(-1)), as an adjuvant to chemotherapy.
      After treatment for 90 days, the higher doses of P10 entrapped within PLGA (5 or
      10 microg.50 microL(-1)) were most effective. Treatment with P10 emulsified in
      Freund's adjuvant (20 microg.50 microL(-1)) or P10 entrapped within PLGA (1
      microg.50 microL(-1)) were accompanied by high levels of interferon-gamma in
      lung. CONCLUSIONS AND IMPLICATIONS: Combination of sulfamethoxazole/trimethoprim
      with the P10 peptide entrapped within PLGA demonstrated increased therapeutic
      efficacy against paracoccidioidomycosis. P10 incorporation into PLGA
      nanoparticles dramatically reduced the peptide amount necessary to elicit a
      protective effect.

PMID- 20136828
TI  - SAR150640, a selective beta3-adrenoceptor agonist, prevents human myometrial
      remodelling and activation of matrix metalloproteinase in an in vitro model of
      chorioamnionitis.
AB  - BACKGROUND AND PURPOSE: The uterine pathophysiology underlying inflammatory
      conditions such as chorioamnionitis remains largely unclear. As we have shown
      that beta(3)-adrenoceptors act as regulators of myometrial inflammation, we
      wanted to investigate the potential role of beta(3)-adrenoceptors in preventing
      uterine remodelling induced by inflammation. EXPERIMENTAL APPROACH: The
      consequences of human chorioamnionitis on myometrial remodelling were
      characterized by Sirius Red staining and metalloproteinase (MMP) expression, and
      compared with the effects of incubating human myometrial samples with Escherichia
      coli lipopolysaccharide (LPS) in vitro. We also assessed the effect of SAR150640,
      a selective beta(3)-adrenoceptor agonist, on the production and activity of MMPs.
      KEY RESULTS: Chorioamnionitis was associated with a 46% decrease in total
      collagen, as well as over-expression of MMP2 (+61%) and MMP9 (+84%); both effects
      were reproduced by incubation with LPS (10 microg x mL(-1), 48 h). LPS-induced
      over-expression of MMP2 and MMP9 in normal human myometrium was paralleled by an
      overactivity of the proteins. Both over-expression and overactivity were
      prevented by the beta(3)-adrenoceptor agonist SAR150640 in a concentration
      dependent manner. SAR150640, by itself, did not exhibit any effect on MMP
      production in control tissues. CONCLUSIONS AND IMPLICATIONS: This study shows
      that inflammation was associated with an intense remodelling of human myometrium,
      a process likely to be explained by MMP activation. Our study emphasizes the
      potential therapeutic relevance of beta(3)-adrenoceptor agonists to the treatment
      of preterm labour and other uterine inflammatory conditions.

PMID- 20136829
TI  - The role of adenosine receptors in regulating production of tumour necrosis
      factor-alpha and chemokines by human lung macrophages.
AB  - BACKGROUND AND PURPOSE: Adenosine is a major endogenous regulator of macrophage
      function, and activates four specific adenosine receptors (A(1), A(2A), A(2B) and
      A(3)). Here, we have assessed in human lung macrophages the modulation of the
      expression of adenosine receptor mRNA by lipopolysaccharide (LPS), and the
      relative contributions of the different adenosine receptors to LPS-induced
      production of tumour necrosis factor (TNF)-alpha and chemokines. EXPERIMENTAL
      APPROACH: Lung macrophages isolated from resected lungs were stimulated with LPS
      and treated with adenosine receptor agonists or/and antagonists. Adenosine
      receptor expression was assessed with qRT-PCR. Cytokines were measured in lung
      macrophage supernatants with elisa. KEY RESULTS: LPS increased (about 400-fold)
      mRNA for A(2A) adenosine receptors, decreased mRNA for A(1) and A(2B), but had no
      effect on A(3) adenosine receptor mRNA. The adenosine receptor agonist NECA
      inhibited TNF-alpha production concentration dependently, whereas the A(1)
      receptor agonist, CCPA, and the A(3) receptor agonist, AB-MECA, inhibited TNF
      alpha production only at concentrations affecting A(2A) receptors. NECA also
      inhibited the production of CCL chemokines (CCL2, CCL3, CCL4, CCL5) and CXCL
      chemokines (CXCL9 and CXCL10), but not that of CXCL1, CXCL8 and CXCL5. Reversal
      of NECA-induced inhibition of TNF-alpha and chemokine production by the selective
      A(2A) adenosine receptor antagonist ZM 241385, but not the A(2B) receptor
      antagonist, MRS 1754, or the A(3) receptor antagonist, MRS 1220, indicated
      involvement of A(2A) receptors. CONCLUSIONS AND IMPLICATIONS: LPS up-regulated
      A(2A) adenosine receptor gene transcription, and this receptor subtype mediated
      inhibition of the LPS-induced production of TNF-alpha and of a subset of
      chemokines in human lung macrophages.

PMID- 20136830
TI  - Nicotinic acetylcholine receptors expressed in the ventralposterolateral thalamic
      nucleus play an important role in anti-allodynic effects.
AB  - BACKGROUND AND PURPOSE: Much interest is currently being focused on the anti
      nociceptive effects mediated by nicotinic acetylcholine (nACh) receptors,
      including their location and mechanism of action. The purpose of this study was
      to elucidate these issues using 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA),
      a nACh receptor agonist, and [(125)I]5IA. EXPERIMENTAL APPROACH: We partially
      ligated the sciatic nerve of Sprague-Dawley rat to induce neuropathic pain
      [Seltzer's partial sciatic nerve ligation (PSL) model]. We then examined the
      changes in nACh receptor density in the CNS using [(125)I]5IA autoradiography and
      the involvement of nACh receptors in anti-nociceptive effects in the region where
      changes occurred. KEY RESULTS: Autoradiographic studies showed that the
      accumulation of [(125)I]5IA and the number of nACh receptors in the thalamus of
      PSL rats were increased about twofold compared with those in the sham-operated
      rats. No change was observed in other brain regions. Rats injected in the ventral
      posterolateral thalamic nucleus (VPL) with 5IA demonstrated a significant and
      dose-dependent anti-allodynic effect and this effect was completely antagonized
      by mecamylamine, injected with 5IA, into the VPL. The blockade of nACh receptors
      in the VPL by mecamylamine decreased by 70% the anti-allodynic effect of 5IA,
      given i.c.v. Moreover, mecamylamine given intra-VPL by itself, induced
      significant hyperalgesia. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that
      the nACh receptors expressed in the VPL play an important role in the anti
      allodynic effects produced by exogenous and endogenous agonists.

PMID- 20136831
TI  - Statins suppress interleukin-6-induced monocyte chemo-attractant protein-1 by
      inhibiting Janus kinase/signal transducers and activators of transcription
      pathways in human vascular endothelial cells.
AB  - BACKGROUND AND PURPOSE: The mechanisms of anti-inflammatory actions of statins, 3
      hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, remain unclear. We
      investigated the effects of statins on interleukin (IL)-6-induced monocyte chemo
      attractant protein (MCP)-1 expression and monocyte chemotaxis. EXPERIMENTAL
      APPROACH: Cultures of human aortic endothelial cells (HAECs) were stimulated with
      IL-6 in the absence and presence of statins. Gene expression and protein
      secretion of MCP-1, phosphorylation of Janus kinase (JAK) and the signal
      transducers and activators of transcription (STAT) pathway, and human monocyte
      migration were examined. KEY RESULTS: IL-6 plus its soluble receptor sIL-6R (IL
      6/sIL-6R) promoted THP-1 monocyte migration, and increased gene expression and
      protein secretion of MCP-1, more than IL-6 alone or sIL-6R alone. Various statins
      inhibited IL-6/sIL-6R-promoted monocyte migration and MCP-1 expression in HAECs.
      Co-incubation of mevalonate and geranylgeranyl pyrophosphate, but not farnesyl
      pyrophosphate, reversed the inhibitory effects of statins on MCP-1 expression.
      Geranylgeranyl transferase inhibitor, but not farnesyl transferase inhibitor,
      suppressed IL-6/sIL-6R-stimulated MCP-1 expression. IL-6/sIL-6R rapidly
      phosphorylated JAK1, JAK2, TYK2, STAT1 and STAT3, which were inhibited by
      statins. Transfection of STAT3 small interfering RNA (siRNA), but not STAT1
      siRNA, attenuated the ability of IL-6/sIL-6R to enhance THP-1 monocyte migration.
      In addition, statins blocked IL-6/sIL-6R-induced translocation of STAT3 to the
      nucleus. CONCLUSIONS AND IMPLICATIONS: Statins suppressed IL-6/sIL-6R-induced
      monocyte chemotaxis and MCP-1 expression in HAECs by inhibiting JAK/STAT
      signalling cascades, explaining why statins have anti-inflammatory properties
      beyond cholesterol reduction.

PMID- 20136832
TI  - 16alpha-Hydroxycleroda-3,13 (14)Z-dien-15,16-olide from Polyalthia longifolia: a
      safe and orally active antileishmanial agent.
AB  - BACKGROUND AND PURPOSE: New antileishmanials from natural products are urgently
      needed due to the emergence of drug resistance complicated by severe cytotoxic
      effects. 16alpha-Hydroxycleroda-3,13 (14)Z-dien-15,16-olide (Compound 1) from
      Polyalthia longifolia was found to be a potential antileishmanial and non
      cytotoxic, as evidenced by long-term survival (>6 months) of treated animals.
      This prompted us to determine its target and, using molecular modelling, identify
      the interactions responsible for its specific antileishmanial activity.
      EXPERIMENTAL APPROACH: In vitro activity of compound was assessed using
      intracellular transgenic green fluorescent protein-stably expressed Leishmania
      donovani parasites. In vivo activity and survival of animals post-treatment were
      evaluated in L. donovani-infected hamsters. Known property of clerodane
      diterpenes as potent human DNA topoisomerase inhibitors led us to evaluate the
      inhibition of recombinant L. donovani topoisomerase I using relaxation assay.
      Mode of cell death induced by Compound 1 was assessed by phosphotidylserine
      exposure post-treatment. Molecular modelling studies were conducted with DNA
      topoisomerase I to identify the binding interactions responsible for its
      activity. KEY RESULTS: Bioassay-guided fractionation led to isolation of Compound
      1 as a non-cytotoxic, orally active antileishmanial. Compound 1 inhibited
      recombinant DNA topoisomerase I which, ultimately, induced apoptosis. Molecular
      docking studies indicated that five strong hydrogen-bonding interactions and
      hydrophobic interactions of Compound 1 with L. donovani DNA-topoisomerase are
      responsible for its antileishmanial activity. CONCLUSIONS AND IMPLICATIONS: The
      data reveal Compound 1 is a potent and safe antileishmanial. The study further
      exploited the structural determinants responsible for its non-cytotoxic and
      potent activity, to raise the feasibility of specifically targeting the target
      enzyme responsible for its activity through rational drug design.

PMID- 20136833
TI  - Fluorescent ligand binding reveals heterogeneous distribution of adrenoceptors
      and 'cannabinoid-like' receptors in small arteries.
AB  - BACKGROUND AND PURPOSE: Pharmacological analysis of synergism or functional
      antagonism between different receptors commonly assumes that interacting
      receptors are located in the same cells. We have now investigated the
      distribution of alpha-adrenoceptors, beta-adrenoceptors and cannabinoid-like
      (GPR55) receptors in the mouse arteries. EXPERIMENTAL APPROACH: Fluorescence
      intensity from vascular tissue incubated with fluorescent ligands (alpha(1)
      adrenoceptor ligand, BODIPY-FL-prazosin, QAPB; beta-adrenoceptor ligand, TMR
      CGP12177; fluorescent angiotensin II; a novel diarylpyrazole cannabinoid ligand
      (Tocrifluor 1117, T1117) was measured with confocal microscopy. Small mesenteric
      and tail arteries of wild-type and alpha(1B/D)-adrenoceptor-KO mice were used.
      KEY RESULTS: T1117, a fluorescent form of the cannabinoid CB(1) receptor
      antagonist AM251, was a ligand for GPR55, with low affinity for CB(1) receptors.
      In mesenteric arterial smooth muscle cells, alpha(1A)-adrenoceptors were
      predominantly located in different cells from those with beta-adrenoceptors,
      angiotensin receptors or cannabinoid-like (GPR55) receptors. Cells with beta
      adrenoceptors predominated at arterial branches. Endothelial cells expressed beta
      adrenoceptors, alpha-adrenoceptors and cannabinoid-like receptors. Only
      endothelial alpha-adrenoceptors appeared in clusters. Adventitia was a rich
      source of G protein-coupled receptors (GPCRs), particularly fibroblasts and nerve
      tracts, where Schwann cells bound alpha-adrenoceptor, beta-adrenoceptor and CB
      receptor ligands, with a mix of separate receptor locations and co-localization.
      CONCLUSIONS AND IMPLICATIONS: Within each cell type, each GPCR had a distinctive
      heterogeneous distribution with limited co-localization, providing a guide to the
      possibilities for functional synergism, and suggesting a new paradigm for
      synergism in which interactions may be either between cells or involve converging
      intracellular signalling processes.

PMID- 20136834
TI  - Mechanisms of multimodal sensing by extracellular Ca(2+)-sensing receptors: a
      domain-based survey of requirements for binding and signalling.
AB  - In this article we consider the molecular basis of sensing and signalling by the
      extracellular calcium-sensing receptor. We consider the nature of its ligands and
      sensing modalities, the identities of its major protein domains and their roles
      in sensing, signalling and trafficking as well as the significance of receptor
      homo- and hetero-dimerization. Finally, we consider the current, incomplete,
      state of knowledge regarding the requirements for ligand-specific signalling.

PMID- 20136835
TI  - Rational design of dualsteric GPCR ligands: quests and promise.
AB  - Dualsteric ligands represent a novel mode of targeting G protein-coupled
      receptors (GPCRs). These compounds attach simultaneously to both, the orthosteric
      transmitter binding site and an additional allosteric binding area of a receptor
      protein. This approach allows the exploitation of favourable characteristics of
      the orthosteric and the allosteric site by a single ligand molecule. The
      orthosteric interaction provides high affinity binding and activation of
      receptors. The allosteric interaction yields receptor subtype-selectivity and, in
      addition, may modulate both, efficacy and intracellular signalling pathway
      activation. Insight into the spatial arrangement of the orthosteric and the
      allosteric site is far advanced in the muscarinic acetylcholine receptor, and the
      design of dualsteric muscarinic agonists has now been accomplished. Using the
      muscarinic receptor as a paradigm, this review summarizes the way from suggestive
      evidence for an orthosteric/allosteric overlap binding to the rational design and
      experimental validation of dualsteric ligands. As allosteric interactions are
      increasingly described for GPCRs and as insight into the spatial geometry of
      ligand/GPCR-complexes is growing impressively, the rational design of dualsteric
      drugs is a promising new approach to achieve fine-tuned GPCR-modulation.

PMID- 20136836
TI  - A comparative analysis of the activity of ligands acting at P2X and P2Y receptor
      subtypes in models of neuropathic, acute and inflammatory pain.
AB  - BACKGROUND AND PURPOSE: This study was undertaken to compare the analgesic
      activity of antagonists acting at P2X1, P2X7, and P2Y12 receptors and agonists
      acting at P2Y1, P2Y2, P2Y4, and P2Y6 receptors in neuropathic, acute, and
      inflammatory pain. EXPERIMENTAL APPROACH: The effect of the wide spectrum P2
      receptor antagonist PPADS, the selective P2X7 receptor antagonist Brilliant Blue
      G (BBG), the P2X1 receptor antagonist (4,4',4'',4-[carbonylbis(imino-5,1,3
      benzenetriyl-bis(carbonylimino))]tetrakis-1,3-benzenedisulfonic acid, octasodium
      salt (NF449) and (8,8'-[carbonylbis(imino-3,1-phenylenecarbonylimino)]bis-1,3,5
      naphthalene-trisulphonic acid, hexasodium salt (NF023), the P2Y12 receptor
      antagonist (2,2-dimethyl-propionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2
      (2,2-dimethyl-propionyloxymethyl)-propylester (MRS2395), the selective P2Y1
      receptor agonist ([[(1R,2R,3S,4R,5S)-4-[6-amino-2-(methylthio)-9H-purin-9-yl]-2,3
      dihydroxybicyclo[3.1.0]hex-1-yl]methyl] diphosphoric acid mono ester trisodium
      salt (MRS2365), the P2Y2/P2Y4 agonist uridine-5'-triphosphate (UTP), and the
      P2Y4/P2Y6 agonist uridine-5'-diphosphate (UDP) were examined on mechanical
      allodynia in the Seltzer model of neuropathic pain, on acute thermal nociception,
      and on the inflammatory pain and oedema induced by complete Freund's adjuvant
      (CFA). KEY RESULTS: MRS2365, MRS2395 and UTP, but not the other compounds,
      significantly alleviated mechanical allodynia in the neuropathic pain model, with
      the following rank order of minimal effective dose (mED) values: MRS2365 >
      MRS2395 > UTP. All compounds had a dose-dependent analgesic action in acute pain
      except BBG, which elicited hyperalgesia at a single dose. The rank order of mED
      values in acute pain was the following: MRS2365 > MRS2395 > NF449 > NF023 > UDP =
      UTP > PPADS. MRS2365 and MRS2395 had a profound, while BBG had a mild effect on
      inflammatory pain, with a following rank order of mED values: MRS2395 > MRS2365 >
      BBG. None of the tested compounds had significant action on oedema evoked by
      intraplantar injection of CFA. CONCLUSIONS AND IMPLICATIONS: Our results show
      that antagonism at P2X1, P2Y12, and P2X7 receptors and agonism at P2Y1 receptors
      define promising therapeutic strategies in acute, neuropathic, and inflammatory
      pain respectively.

PMID- 20136837
TI  - Dynamic monitoring of NET activity in mature murine sympathetic terminals using a
      fluorescent substrate.
AB  - BACKGROUND AND PURPOSE: To validate a fluorescence approach for monitoring
      norepinephrine transporter (NET) transport rate in mature sympathetic terminals,
      and to determine how prejunctional muscarinic receptors affect NET rate.
      EXPERIMENTAL APPROACH: Confocal imaging of a fluorescent NET substrate
      [neurotransmitter transporter uptake assay (NTUA)] as it accumulates in the
      mature sympathetic nerve terminals of the mouse isolated vas deferens.
      Fluorescence recovery after photobleaching (FRAP), enhanced green fluorescence
      protein (EGFP)-transgenic mice and contraction studies were also used. KEY
      RESULTS: NTUA fluorescence accumulated linearly in nerve terminals, an effect
      that was prevented with NET inhibition with desipramine (1 microM). Such
      accumulation was reversed by amphetamine (10 microM), which is known to reverse
      the direction of transport of NET substrates. NTUA labelling was not present in
      cholinergic terminals (identified using EGFP fluorescence expressed in transgenic
      mice under a choline acetyltransferase promoter). FRAP experiments, altered nerve
      terminal distribution with reserpine pretreatment and co-imaging in terminals
      filled with a cytoplasmic marker (Alexa 594 dextran) indicated that the NTUA
      labelling was largely confined to vesicles within varicosities; vesicular
      exchange between varicosities was rare. The rate of NTUA accumulation was slower
      in the presence of the muscarinic agonist carbachol (10 microM) demonstrating
      muscarinic inhibition of NET rate. CONCLUSIONS AND IMPLICATIONS: A
      straightforward protocol now exists to monitor NET transport rate at the level of
      the single nerve terminal varicosity, providing a useful tool to understand the
      physiology of NET regulation, the action of NET inhibitors on mature sympathetic
      terminals, dynamic vesicular tracking and to identify sympathetic terminals from
      mixed terminal populations in living organs.

PMID- 20136838
TI  - Genistein reduces glycosaminoglycan levels in a mouse model of
      mucopolysaccharidosis type II.
AB  - BACKGROUND AND PURPOSE: Mucopolysaccharidoses (MPS) are lysosomal storage
      disorders resulting from a deficit of specific lysosomal enzymes catalysing
      glycosaminoglycan (GAG) degradation. The typical pathology involves most of the
      organ systems, including the brain, in its severe forms. The soy isoflavone
      genistein has recently attracted considerable attention as it can reduce GAG
      synthesis in vitro. Furthermore, genistein is able to cross the blood-brain
      barrier in the rat. The present study was undertaken to assess the ability of
      genistein to reduce urinary and tissue GAG levels in vivo. EXPERIMENTAL APPROACH:
      We used mice with genetic deletion of iduronate-2-sulphatase (one of the GAG
      catabolizing enzymes) which provide a model of MPS type II. Two doses of
      genistein, 5 or 25 mg.kg(-1).day(-1), were given, in the diet for 10 or 20 weeks.
      Urinary and tissue GAG content was evaluated by biochemical and histochemical
      procedures. KEY RESULTS: Urinary GAG levels were reduced after 10 weeks'
      treatment with genistein at either 5 or 25 mg.kg(-1).day(-1). In tissue samples
      from liver, spleen, kidney and heart, a reduction in GAG content was observed
      with both dosages, after 10 weeks' treatment. Decreased GAG deposits in brain
      were observed after genistein treatment in some animals. CONCLUSIONS AND
      IMPLICATIONS: There was decreased GAG storage in the MPSII mouse model following
      genistein administration. Our results would support the use of this plant-derived
      isoflavone in a combined therapeutic protocol for treatment of MPS.

PMID- 20136839
TI  - Inhalational anaesthetics and n-alcohols share a site of action in the neuronal
      Shaw2 Kv channel.
AB  - BACKGROUND AND PURPOSE: Neuronal ion channels are key targets of general
      anaesthetics and alcohol, and binding of these drugs to pre-existing and
      relatively specific sites is thought to alter channel gating. However, the
      underlying molecular mechanisms of this action are still poorly understood. Here,
      we investigated the neuronal Shaw2 voltage-gated K(+) (K(v)) channel to ask
      whether the inhalational anaesthetic halothane and n-alcohols share a binding
      site near the activation gate of the channel. EXPERIMENTAL APPROACH: Focusing on
      activation gate mutations that affect channel modulation by n-alcohols, we
      investigated n-alcohol-sensitive and n-alcohol-resistant K(v) channels
      heterologously expressed in Xenopus oocytes to probe the functional modulation by
      externally applied halothane using two-electrode voltage clamping and a gas-tight
      perfusion system. KEY RESULTS: Shaw2 K(v) channels are reversibly inhibited by
      halothane in a dose-dependent and saturable manner (K(0.5)= 400 microM; n(H)=
      1.2). Also, discrete mutations in the channel's S4S5 linker are sufficient to
      reduce or confer inhibition by halothane (Shaw2-T330L and K(v)3.4-G371I/T378A
      respectively). Furthermore, a point mutation in the S6 segment of Shaw2 (P410A)
      converted the halothane-induced inhibition into halothane-induced potentiation.
      Lastly, the inhibition resulting from the co-application of n-butanol and
      halothane is consistent with the presence of overlapping binding sites for these
      drugs and weak binding cooperativity. CONCLUSIONS AND IMPLICATIONS: These
      observations strongly support a molecular model of a general anaesthetic binding
      site in the Shaw2 K(v) channel. This site may involve the amphiphilic interface
      between the S4S5 linker and the S6 segment, which plays a pivotal role in K(v)
      channel activation.

PMID- 20136840
TI  - Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan
      induced knee joint synovitis in the rat.
AB  - BACKGROUND AND PURPOSE: Recent findings suggest that the noxious gas H(2)S is
      produced endogenously, and that physiological concentrations of H(2)S are able to
      modulate pain and inflammation in rodents. This study was undertaken to evaluate
      the ability of endogenous and exogenous H(2)S to modulate carrageenan-induced
      synovitis in the rat knee. EXPERIMENTAL APPROACH: Synovitis was induced in Wistar
      rats by intra-articular injection of carrageenan into the knee joint. Sixty
      minutes prior to carrageenan injection, the rats were pretreated with
      indomethacin, an inhibitor of H(2)S formation (DL-propargylglycine) or an H(2)S
      donor [Lawesson's reagent (LR)]. KEY RESULTS: Injection of carrageenan evoked
      knee inflammation, pain as characterized by impaired gait, secondary tactile
      allodynia of the ipsilateral hindpaw, joint swelling, histological changes,
      inflammatory cell infiltration, increased synovial myeloperoxidase, protein
      nitrotyrosine residues, inducible NOS (iNOS) activity and NO production.
      Pretreatment with LR or indomethacin significantly attenuated the pain responses,
      and all the inflammatory and biochemical changes, except for the increased iNOS
      activity, NO production and 3-NT. Propargylglycine pretreatment potentiated
      synovial iNOS activity (and NO production), and enhanced macrophage infiltration,
      but had no effect on other inflammatory parameters. CONCLUSIONS AND IMPLICATIONS:
      Whereas exogenous H(2)S delivered to the knee joint can produce a significant
      anti-inflammatory and anti-nociceptive effect, locally produced H(2)S exerts
      little immunomodulatory effect. These data further support the development and
      use of H(2)S donors as potential alternatives (or complementary therapies) to the
      available anti-inflammatory compounds used for treatment of joint inflammation or
      relief of its symptoms.

PMID- 20136841
TI  - GPR55 ligands promote receptor coupling to multiple signalling pathways.
AB  - BACKGROUND AND PURPOSE: Although GPR55 is potently activated by the endogenous
      lysophospholipid, L-alpha-lysophosphatidylinositol (LPI), it is also thought to
      be sensitive to a number of cannabinoid ligands, including the prototypic CB1
      receptor antagonists AM251 and SR141716A (Rimonabant). In this study we have used
      a range of functional assays to compare the pharmacological activity of selected
      cannabinoid ligands, AM251, AM281 and SR141716A with LPI in a HEK293 cell line
      engineered to stably express recombinant, human GPR55. EXPERIMENTAL APPROACH: We
      evaluated Ca(2+) signalling, stimulation of extracellular signal regulated kinase
      (ERK1/2) mitogen activated kinase MAP-kinases, induction of transcriptional
      regulators that are downstream of GPR55, including nuclear factor of activated T
      cells (NFAT), nuclear factor-kappaB (NF-kappaB) and cAMP response element binding
      protein (CREB), as well as receptor endocytosis. In addition, we assessed the
      suitability of a novel, label-free assay for GPR55 ligands that involves optical
      measurement of dynamic mass redistribution following receptor activation. KEY
      RESULTS: GPR55 linked to a range of downstream signalling events and that the
      activity of GPR55 ligands was influenced by the functional assay employed, with
      differences in potency and efficacy observed. CONCLUSIONS AND IMPLICATIONS: Our
      data help to resolve some of the issues surrounding the pharmacology of
      cannabinoid ligands at GPR55 and highlight some differences in effector coupling
      associated with distinct GPR55 ligands.

PMID- 20136843
TI  - N-arachidonoyl glycine, an endogenous lipid that acts as a vasorelaxant via
      nitric oxide and large conductance calcium-activated potassium channels.
AB  - BACKGROUND AND PURPOSE: N-arachidonoyl glycine (NAGly) is an endogenous lipid
      that is structurally similar to the endocannabinoid, N-arachidonoyl ethanolamide
      (anandamide). While NAGly does not activate cannabinoid receptors, it exerts
      cannabimimetic effects in pain regulation. Here, we have determined if NAGly,
      like anandamide, modulates vascular tone. EXPERIMENTAL APPROACH: In rat isolated
      small mesenteric arteries, the relaxant responses to NAGly were characterized.
      Effects of N-arachidonoyl serine and N-arachidonoyl gamma-aminobutyric acid were
      also examined. KEY RESULTS: In endothelium-intact arteries, NAGly-induced
      relaxation (pEC(50%)= 5.7 +/- 0.2; relaxation at 30 microM = 98 +/- 1%) was
      attenuated by l-NAME (a nitric oxide synthase inhibitor) or iberiotoxin
      [selective blocker of large conductance Ca(2+)-activated K(+) channels (BK(Ca))],
      and abolished by high extracellular K(+) concentration. Endothelial removal
      reduced the potency of NAGly, and the resultant relaxation was inhibited by
      iberiotoxin, but not l-NAME. NAGly responses were sensitive to the novel
      cannabinoid receptor antagonist O-1918 independently of endothelial integrity,
      whereas pertussis toxin, which uncouples G(i/o) proteins, attenuated NAGly
      relaxation only in endothelium-intact arteries. Treatments with antagonists for
      CB(1), CB(2) and TRPV1 receptors, or inhibitors of fatty acid amide hydrolase and
      COX had no effect. The two other arachidonoyl amino acids also induced
      iberiotoxin- and L-NAME-sensitive relaxations. CONCLUSION AND IMPLICATIONS: NAGly
      acts as a vasorelaxant predominantly via activation of BK(Ca) in rat small
      mesenteric arteries. We suggest that NAGly activates an unknown G(i/o)-coupled
      receptor, stimulating endothelial release of nitric oxide which in turn activates
      BK(Ca) in the smooth muscle. In addition, NAGly might also activate BK(Ca)
      through G(i/o)- and nitric oxide-independent mechanisms.

PMID- 20136844
TI  - Vasodilator therapy with hydralazine induces angiotensin AT receptor-mediated
      cardiomyocyte growth in mice lacking guanylyl cyclase-A.
AB  - BACKGROUND AND PURPOSE: Recent clinical guidelines advocate the use of the
      isosorbide dinitrate/hydralazine combination in treatment for heart failure.
      However, clinical and laboratory evidence suggest that some vasodilators may
      induce cardiac hypertrophy under uncertain conditions. This study investigated
      the effects and underlying mechanism of action of the vasodilator hydralazine on
      cardiac growth. EXPERIMENTAL APPROACH: Wild-type mice and animals deficient in
      guanylyl cyclase-A (GCA) and/or angiotensin receptors (AT(1) and AT(2) subtypes)
      were treated with hydralazine ( approximately 24 mg.kg(-1).day(-1) in drinking
      water) for 5 weeks. Cardiac mass and/or cardiomyocyte cross-sectional area,
      fibrosis (van Giessen-staining) and cardiac gene expression (real-time RT-PCR)
      were measured. KEY RESULTS: Hydralazine lowered blood pressure in mice of all
      genotypes. However, this treatment increased the heart and left ventricular to
      body weight ratios, as well as cardiomyocyte cross-sectional area, and cardiac
      expression of atrial natriuretic peptide mRNA in mice lacking GCA. Hydralazine
      did not affect cardiac hypertrophy in wild-type mice and mice lacking either
      AT(1) or AT(2) receptors alone. However, the pro-hypertrophic effect of
      hydralazine was prevented in mice lacking both GCA and AT(2), but not GCA and
      AT(1) receptors. However, hydralazine did decrease cardiac collagen deposition
      and collagen I mRNA (signs of cardiac fibrosis) in mice that were deficient in
      GCA, or both GCA and AT(2) receptors. CONCLUSIONS AND IMPLICATIONS: The
      vasodilator hydralazine induced AT(2) receptor-mediated cardiomyocyte growth
      under conditions of GCA deficiency. However, attenuation of cardiac fibrosis by
      hydralazine could be beneficial in the management of cardiac diseases.

PMID- 20136842
TI  - Non-synaptic receptors and transporters involved in brain functions and targets
      of drug treatment.
AB  - Beyond direct synaptic communication, neurons are able to talk to each other
      without making synapses. They are able to send chemical messages by means of
      diffusion to target cells via the extracellular space, provided that the target
      neurons are equipped with high-affinity receptors. While synaptic transmission is
      responsible for the 'what' of brain function, the 'how' of brain function (mood,
      attention, level of arousal, general excitability, etc.) is mainly controlled non
      synaptically using the extracellular space as communication channel. It is
      principally the 'how' that can be modulated by medicine. In this paper, we
      discuss different forms of non-synaptic transmission, localized spillover of
      synaptic transmitters, local presynaptic modulation and tonic influence of
      ambient transmitter levels on the activity of vast neuronal populations. We
      consider different aspects of non-synaptic transmission, such as synaptic
      extrasynaptic receptor trafficking, neuron-glia communication and retrograde
      signalling. We review structural and functional aspects of non-synaptic
      transmission, including (i) anatomical arrangement of non-synaptic release sites,
      receptors and transporters, (ii) intravesicular, intra- and extracellular
      concentrations of neurotransmitters, as well as the spatiotemporal pattern of
      transmitter diffusion. We propose that an effective general strategy for
      efficient pharmacological intervention could include the identification of
      specific non-synaptic targets and the subsequent development of selective
      pharmacological tools to influence them.

PMID- 20136845
TI  - The COX-2 inhibitors, meloxicam and nimesulide, suppress neurogenesis in the
      adult mouse brain.
AB  - BACKGROUND AND PURPOSE: In adults, neurogenesis persists in the hippocampus and
      the subventricular zone (SVZ), and this is important for learning and memory.
      Inhibitors of COX-2 suppress ischaemia-induced neurogenesis in the hippocampus.
      Here, we have determined the effects of COX-2 inhibitors on neurogenesis
      throughout the normal adult mouse brain. EXPERIMENTAL APPROACH: Young adult mice
      were treated with COX-2 inhibitors, and the proliferation of neural progenitor
      cells was measured in the SVZ and hippocampus. In addition, the local uptake of
      lentiviral vectors in the rostral migratory stream enabled the formation of new
      neurons in the olfactory bulb (OB) to be assessed. KEY RESULTS: The COX-2
      inhibitor meloxicam suppressed progenitor cell proliferation in the SVZ and
      hippocampus. A significant decrease in the appearance of new neurons in the OB
      was also observed. Similar effects on progenitor proliferation in the SVZ were
      seen with nimesulide. The absence of COX-2 expression in the proliferating
      progenitors in vivo, and the lack of effect of the COX-2 inhibitors on the growth
      rate of a cultured progenitor cell line, suggest that the effect is indirect. The
      specific expression of COX-2 in resting microglia that closely associate with the
      proliferating progenitor cells provides for a possible site of action.
      CONCLUSIONS AND IMPLICATIONS: Treatment with a COX-2 inhibitor results in a
      substantial inhibition of adult neurogenesis. Studies on human tissues are
      warranted in order to determine if this effect extends to humans, and whether
      inhibition of neurogenesis should be considered as an adverse effect of these
      drugs.

PMID- 20136846
TI  - A role for transient receptor potential vanilloid 4 in tonicity-induced
      neurogenic inflammation.
AB  - BACKGROUND AND PURPOSE: Changes in extracellular fluid osmolarity, which occur
      after tissue damage and disease, cause inflammation and maintain chronic
      inflammatory states by unknown mechanisms. Here, we investigated whether the
      osmosensitive channel, transient receptor potential vanilloid 4 (TRPV4), mediates
      inflammation to hypotonic stimuli by a neurogenic mechanism. EXPERIMENTAL
      APPROACH: TRPV4 was localized in dorsal root ganglia (DRG) by immunofluorescence.
      The effects of TRPV4 agonists on release of pro-inflammatory neuropeptides from
      peripheral tissues and on inflammation were examined. KEY RESULTS: Immunoreactive
      TRPV4 was detected in DRG neurones innervating the mouse hindpaw, where it was co
      expressed in some neurones with CGRP and substance P, mediators of neurogenic
      inflammation. Hypotonic solutions and 4alpha-phorbol 12,13-didecanoate, which
      activate TRPV4, stimulated neuropeptide release in urinary bladder and airways,
      sites of neurogenic inflammation. Intraplantar injection of hypotonic solutions
      and 4alpha-phorbol 12,13-didecanoate caused oedema and granulocyte recruitment.
      These effects were inhibited by a desensitizing dose of the neurotoxin capsaicin,
      antagonists of CGRP and substance P receptors, and TRPV4 gene knockdown or
      deletion. In contrast, antagonism of neuropeptide receptors and disruption of
      TRPV4 did not prevent this oedema. TRPV4 gene knockdown or deletion also markedly
      reduced oedema and granulocyte infiltration induced by intraplantar injection of
      formalin. CONCLUSIONS AND IMPLICATIONS: Activation of TRPV4 stimulates
      neuropeptide release from afferent nerves and induces neurogenic inflammation.
      This mechanism may mediate the generation and maintenance of inflammation after
      injury and during diseases, in which there are changes in extracellular
      osmolarity. Antagonism of TRPV4 may offer a therapeutic approach for inflammatory
      hyperalgesia and chronic inflammation.

PMID- 20136847
TI  - High frequencies of less differentiated and more proliferative WT1-specific CD8+
      T cells in bone marrow in tumor-bearing patients: an important role of bone
      marrow as a secondary lymphoid organ.
AB  - In tumor-bearing patients, tumor-associated antigen (TAA)-specific CTLs are
      spontaneously induced as a result of immune response to TAAs and play an
      important role in anti-tumor immunity. Wilms' tumor gene 1 (WT1) is overexpressed
      in various types of tumor and WT1 protein is a promising pan-TAA because of its
      high immunogenicity. In this study, to clarify the immune response to the WT1
      antigen, WT1-specific CD8(+) T cells that were spontaneously induced in patients
      with solid tumor were comparatively analyzed in both bone marrow (BM) and
      peripheral blood (PB). WT1-specific CD8(+) T cells more frequently existed in BM
      than in PB, whereas frequencies of naive (CCR7(+) CD45RA(+)), central memory
      (CCR7(+) CD45RA-), effector-memory (CCR7- CD45RA(-)), and effector (CCR7-
      CD45RA(+)) subsets were not significantly different between BM and PB. However,
      analysis of these subsets for the expression of CD57 and CD28, which were
      associated with differentiation, revealed that effector-memory and effector
      subsets of the WT1-specific CD8(+) T cells in BM had less differentiated
      phenotypes and more proliferative potential than those in PB. Furthermore,
      CD107a/b functional assay for WT1 peptide-specific cytotoxic potential and
      carboxyfluorescein diacetate succinimidyl ester dilution assay for WT1 peptide
      specific proliferation also showed that WT1-specific CD8(+) T cells in BM were
      less cytotoxic and more proliferative in response to WT1 peptide than those in
      PB. These results implied that BM played an important role as a secondary
      lymphoid organ in tumor-bearing patients. Preferential residence of WT1-specific
      CD8(+) T cells in BM could be, at least in part, explained by higher expression
      of chemokine receptor CCR5, whose ligand was expressed on BM fibroblasts on the
      WT1-specific CD8(+) T cells in BM, compared to those in PB. These results should
      provide us with an insight into WT1-specific immune response in tumor-bearing
      patients and give us an idea of enhancement of clinical response in WT1 protein
      targeted immunotherapy.

PMID- 20136848
TI  - A novel homozygous point mutation at codon 82 (HBB:c.247A > T) in the beta-globin
      gene leads to thalassemia major.

PMID- 20136849
TI  - Evaluation of mean sphered corpuscular volume for predicting hereditary
      spherocytosis.
AB  - Hereditary spherocytosis (HS) is a common red blood cell disorder. It has been
      shown that the mean sphered corpuscular volume (MSCV), an artificial volume, is
      always lower than the MCV in HS and also in some autoimmune haemolytic anaemia
      (AIHA). Our purpose was to assess the reliability of MSCV in routine practise,
      and its relevance in screening for HS. Comparison of MSCV and MCV was undertaken
      in a prospective study of 366 patients with anaemia. In addition, included were
      patients previously diagnosed to have HS (n = 33) or AIHA (n = 16). When MSCV was
      lower than MCV, a flow cytometric (FC) test for HS was performed. Delta (MCV
      MSCV) values >9.6 fl were obtained for all HS patients. A wider spread of delta
      (MCV-MSCV) values was obtained for AIHA patients whose red cells gave FC test
      results negative for HS. In the ROC curve analysis, the determination of delta
      (MCV-MSCV) value has a 90.57% specificity and 100% sensitivity for HS. MSCV is a
      reliable automated parameter indicating possible HS. When a delta (MCV-MSCV)
      value is >9.6 fl, the FC test and the Coombs test are required in the
      differential diagnosis of HS and some AIHA.

PMID- 20136851
TI  - Pediatric interventional cardiology in the United States is dependent on the off
      label use of medical devices.
AB  - OBJECTIVE: A substantial unmet medical device need exists in pediatric care. As a
      result, the off-label use of approved devices is routine in pediatric
      interventional cardiology, but the extent and nature of this practice has not
      been previously described. The purpose of this study, therefore, is to evaluate
      the prevalence and nature of off-label cardiac device use in an active pediatric
      interventional program in the United States. STUDY DESIGN: This study is a
      retrospective review of all interventional cardiac procedures performed at our
      institution from July 1, 2005 to June 30, 2008. Diagnostic (noninterventional)
      catheterizations, myocardial biopsies, invasive electrophysiology studies, and
      studies involving investigational devices were excluded. Interventions performed
      were compared with the manufacturer's labeled indications for each device.
      RESULTS: During this 3-year period, 473 patients (median age 4.1 years) underwent
      595 transcatheter interventions. An approved device was utilized for an off-label
      application in 63% of patients, and in 50% of all interventions performed. The
      most frequent off-label procedures were stent implantations (99% off-label),
      balloon dilations (78% off-label), and coil embolizations (29% off-label). In
      contrast, the off-label use of septal and ductal occluders was relatively
      uncommon. CONCLUSIONS: In our routine (noninvestigational) practice of pediatric
      interventional cardiology, 63% of patients underwent procedures utilizing medical
      devices for off-label indications. These data underscore the need to enhance
      cardiac device review and approval processes in the United States to include
      pediatric applications.

PMID- 20136852
TI  - Three-stage palliation of hypoplastic left heart syndrome in the University
      HealthSystem Consortium.
AB  - OBJECTIVE: The objective of this study was to describe current management and
      short-term outcomes for patients with hypoplastic left heart syndrome
      representative of nationwide experience. Additionally, this study identifies risk
      factors associated with mortality in patients undergoing staged surgical
      palliation. DESIGN: The University HealthSystem Consortium database was queried
      to identify all hospital admissions between 1998 and 2007 with a diagnosis of
      hypoplastic left heart syndrome. Procedure codes were used to determine surgical
      management, and outcomes were ascertained by discharge status (discharged,
      transferred, or expired). RESULTS: Discharge data were present from 118 hospitals
      in the United States. First-stage surgical palliation was performed in 1949
      neonates with 30% mortality. Mortality decreased from 43% in 1998 to 18% in 2007.
      Large institutional case volume and later era of surgery were associated with
      improved operative mortality in first-stage palliation. Primary cardiac
      transplantation was performed in 28 neonates, and rescue transplantation in 11,
      with 36% mortality. Second-stage palliation was performed in 1244 patients with
      5.2% mortality, and third-stage palliation was performed in 1084 patients with
      4.1% mortality. An additional 62 patients over 1 month of age at time of
      admission received cardiac transplantation with 15% mortality. CONCLUSIONS: First
      stage palliative mortality for hypoplastic left heart syndrome fell dramatically
      over the past decade, while that for second- and third-stage procedures remained
      stable. The cumulative operative mortality for three-staged repair of hypoplastic
      left heart syndrome was 39% over the decade, but fell to 24% for procedures in
      2007.

PMID- 20136853
TI  - Following the arterial switch operation, obese children have risk factors for
      early cardiovascular disease.
AB  - BACKGROUND: Children who have undergone the arterial switch operation (ASO) are
      at risk for premature coronary artery disease due to coronary re-implantation.
      Obesity may also pose cardiovascular risk. The purpose of this study was to
      evaluate comorbidities and markers of early cardiovascular disease in obese ASO
      patients. METHODS: Obese [body mass index (BMI) >or= 95th %] and normal weight
      (NW, BMI < 85th %) ASO patients, and NW controls without heart disease were
      enrolled, and underwent prospective vascular, echocardiographic, laboratory,
      exercise, and ambulatory blood pressure (BP) testing. Results were compared
      between groups. BP load was defined as proportion of recordings >or= 95th %.
      RESULTS: Thirty patients [13.2 years (11.2-16.8), 57% male] were evaluated: 10
      obese ASO, 10 NW ASO, and 10 NW controls. Obese ASO patients, in comparison to NW
      ASO and controls, had higher systolic BP% [96% (90-99) vs. 67% (30-91) P= 0.07
      (trend) and 34% (21-43) P= 0.005], night-time diastolic BP load [18% (14-24) vs.
      0% (0-0) P= 0.01 and 0% (0-0) P= 0.01], left ventricular mass index [51.7
      g/m(2.7) (46.6-53.3) vs. 40.7 g/m(2.7) (29.2-41.6) P < 0.01 and 28.9 g/m(2.7)
      (27.3-33.7) P < 0.01], and lower brachial artery reactivity [8.7% (6.2-11.9) vs.
      14.6% (10.8-23.0) P= 0.03, and 16.7% (12.8-17.8) P= 0.05]. There was a trend
      toward increased carotid intima-media thickness, and significantly higher
      triglyceride and lower high-density lipoprotein levels in obese ASO patients.
      CONCLUSIONS: Following the ASO, obese patients have associated comorbidities, and
      markers of early cardiovascular disease. These may pose additional risk for
      future cardiovascular events in this unique population who underwent coronary
      artery re-implantation in infancy.

PMID- 20136855
TI  - Long-term follow up of secundum atrial septal defect closure with the amplatzer
      septal occluder.
AB  - BACKGROUND: During the past 15 years, closure of a secundum atrial septal defect
      (ASD) has moved from a surgical to a percutaneous transcatheter approach. Few
      long-term studies of the efficacy and safety of closure of an ASD by an Amplatzer
      septal occluder (ASO) exist. METHODS: To examine the long-term results of
      secundum ASD closure using the ASO, data on 94 patients who underwent secundum
      ASD closure with the ASO between 1998 and 2002 were available and reviewed. Data
      regarding residual shunt, chest pain, palpitations, arrhythmias, headaches,
      transient ischemic attacks, cerebrovascular accidents, and mortality were
      collected. RESULTS: Seven (7.4%) subjects had residual shunts immediately
      following ASO placement. During follow-up, 4 residual shunts closed for a
      complete closure rate of 97%. Eighteen (19%) patients reported chest pain during
      the follow-up period. Twenty-three patients (24%) reported palpitations during
      the follow up period, 7 were documented arrhythmias, including supraventricular
      tachycardia, atrial fibrillation, and premature ventricular beats. Migraine
      headaches were new-onset in 4 patients. Migraine cessation occurred in 2 patients
      after secundum ASD closure. One child died from a cerebral vascular event 18
      months following device placement. Only 1 patient developed mild aortic
      insufficiency. CONCLUSION: These data indicate that for up to 120 months of
      patient follow-up, the ASO continues to be a safe device. Residual shunts and
      arrhythmias have low incidence post-ASO placement. Given the mortality in one
      high-risk patient, further investigation into anti-platelet therapy after device
      placement is warranted.

PMID- 20136854
TI  - Morphologic, mechanical, conductive, and hemodynamic changes following
      transcatheter closure of atrial septal defect.
AB  - OBJECTIVE: The secundum type of atrial septal defect (ASD) is a common congenital
      cardiac anomaly. Transcatheter closure of the defect is the preferable
      therapeutic approach to avoid potential future complications. This work extends
      the data collected so far regarding the electrocardiographic, morphologic,
      hemodynamic, and mechanical changes following the procedure. DESIGN: From April
      2002 to October 2003, 42 consecutive patients underwent successful transcatheter
      closure of secundum type ASD. They were sampled for different parameters by
      transthoracic echocardiography before the procedure and at three different points
      over the next 4 years, and analyzed in two age groups: children and adults.
      RESULTS: The dimensions of the chambers normalized throughout the study period.
      Abnormal movement of the interventricular septum normalized mostly during the
      first month, but its thickness increased gradually to normal levels during the 4
      years of the study. High elevated pulmonary artery pressure values began
      declining to near normal levels from the second month following the procedure.
      The stroke volume and the right bundle branch block pattern improved throughout
      the study period. CONCLUSIONS: Transcatheter ASD closure is followed by
      morphologic, conductive, and hemodynamic changes at different time intervals
      during the first years and results in normalization or near normalization of the
      heart's structure and function.

PMID- 20136856
TI  - Adults with Down syndrome: safety and long-term outcome of cardiac operation.
AB  - OBJECTIVE: As limited data exist, we sought to review the safety and outcome of
      cardiac surgery in the adult Down syndrome population. DESIGN: We reviewed the
      data of all patients >or=18 years old with Down syndrome who underwent cardiac
      surgery (1969-2008) at our hospital. RESULTS: Fifty patients underwent 57
      surgeries (mean age 33 years). Fifteen patients had prior cardiac operations in
      childhood: 7 complete and 1 partial atrioventricular canal, 2 secundum atrial
      septal defect, 2 Tetralogy of Fallot, 1 patent ductus arteriosus, 1 combined
      atrioventricular canal and Tetralogy of Fallot, and 1 ventricular septal defect.
      Operations in adult Down syndrome patients included repair of partial
      atrioventricular canal in 17, aortic valve replacement in 7, mitral valve
      replacement/repair in 7, ventricular septal defect in 6, atrial septal defect in
      3, Tetralogy of Fallot in 3, pulmonary valve replacement in 3, and other in 11.
      There was 1 in-hospital death (1.8%) from multiorgan failure. The mean hospital
      stay was 10.6 days. Average ventilatory support was 2.4 days (range 0-32). Atrial
      arrhythmias occurred in 14 patients (25%). Six patients had early postoperative
      pulmonary infections. Mean follow-up was 6 years, maximum 29 years. There were
      eight late deaths at an average age of 52 years (range 30-58) occurring 15 years
      postoperatively (range 32 days-29 years); two in the setting of dementia (mean
      age 56 years). CONCLUSION: At an experienced center, adult patients with Down
      syndrome can undergo cardiac surgery with a low risk of mortality and acceptable
      morbidity. Atrial arrhythmias and pulmonary infections are common
      postoperatively.

PMID- 20136857
TI  - Rehabilitation program in adult congenital heart disease patients with pulmonary
      hypertension.
AB  - INTRODUCTION: It is commonly believed that physical activity may have a negative
      impact on pulmonary hypertension patients. The object of this study is to
      determine the tolerability of a directed exercise program in congenital heart
      disease patients with pulmonary hypertension. METHODS: Eight congenital heart
      disease patients with pulmonary hypertension were studied and followed up during
      a 1-year period. Four of them were enrolled in a 3-month rehabilitation program.
      RESULTS: No significant changes in analytical data, hand and leg strength, or
      quality of life were seen at the end of the training program in rehabilitation
      and nonrehabilitation patients. However, patients in the rehabilitation group
      improved 6 minutes' walk test minimum hemoglobin oxygen saturation and functional
      class after ending the training program without having adverse events such as
      progression of symptoms or heart failure. CONCLUSIONS: Cardiopulmonary
      rehabilitation appears to be a safe intervention in patients with congenital
      heart disease and pulmonary hypertension.

PMID- 20136858
TI  - Management of a fetal intrapericardial teratoma: a case report and review of the
      literature.
AB  - Intrapericardial teratomas are rare but potentially fatal. With prenatal
      ultrasound, early diagnosis and decision for treatment can be accomplished.
      However, the decision becomes to treat prenatally vs. waiting until the neonatal
      period for definitive surgical management. The most common sequelae of
      intrapericardial teratomas are pericardial effusion and often progression to
      hydrops. It is these sequelae that tend to guide management. Presented here is a
      case report of the diagnosis and management of a twin fetus with an
      intrapericardial teratoma, as well as a review of the literature.

PMID- 20136859
TI  - Single coronary artery with right ventricular fistula: case report and literature
      review.
AB  - We report a rare case of a 6-year-old boy who was diagnosed with coronary artery
      fistulae communicating with the right ventricle and a left single coronary
      artery. Preoperative angiography showed a dilated and tortuous single coronary
      artery draining into the right ventricle. Two coronary artery fistulae draining
      into the right ventricle were detected at operation and both of these were
      ligated. Postoperative angiography showed that the single coronary artery
      diameter was almost normalized, although the vessel was still slightly tortuous.
      His clinical course was uneventful. In this report, we summarize cases of
      coronary artery fistula with single coronary artery that have been reported in
      the literature as well as our case.

PMID- 20136860
TI  - Perventricular closure of a large ventricular septal defect in congenitally
      corrected transposition of the great arteries.
AB  - We report the case of a 30 year-old male with congenitally corrected
      transposition of the great arteries, atrial, and ventricular septal defects
      (VSD), and pulmonary stenosis. He previously underwent three palliative surgical
      procedures before undergoing intracardiac repair at age 20 with a left
      ventricular to pulmonary artery (LV-PA) conduit, VSD closure, and replacement of
      the systemic atrioventricular valve. A residual VSD was noted postoperatively. He
      did well for approximately 10 years when he started becoming more breathless with
      daily activities and was noted to have a resting room air oxygen saturation of
      85%. Despite increased diuretic therapy he continued to deteriorate and was
      ultimately admitted to the hospital in florid right and left heart failure with
      recurrent atrial fibrillation. Catheterization revealed pulmonary hypertension
      (pulmonary artery pressure = 80/17 mm Hg), moderate conduit stenosis, severe
      pulmonic regurgitation, and oxygen saturation of 75%. Calculated shunt fraction
      (Qp : Qs) was 1.3:1. He was referred for surgical intervention, specifically, LV
      PA conduit replacement, oversewing of the pulmonic valve, VSD closure, and
      pacemaker placement. Intraoperatively, the VSD could not be closed despite
      multiple attempts through various approaches. Therefore, perventricular VSD
      closure using two Amplatzer septal occluders (AGA Medical, Golden Valley, MN) was
      performed in the operating room with the chest open off cardiopulmonary bypass.
      Following deployment, the residual shunt was small and the inferior vena cava-to
      pulmonary artery saturation step-up was only 4%. The left ventricular systolic
      pressure decreased to one half systemic. This case highlights the utility and
      efficacy of a hybrid approach in the treatment of complex congenital heart
      disease.

PMID- 20136861
TI  - Cryothermal catheter ablation of atrioventricular nodal reentrant tachycardia in
      a pediatric patient after atrioventricular canal repair.
AB  - Anatomic displacement of the atrioventricular node and associated conduction
      tissue in atrioventricular septal defects has been previously described. In spite
      of the increasing use of cryothermal catheter ablation in the pediatric
      population, there remains very little literature regarding its use in congenital
      heart disease. We describe successful cryothermal modification of the slow
      atrioventricular nodal pathway in a 12-year-old patient with a previously
      repaired partial atrioventricular septal defect and inducible atrioventricular
      nodal reentrant tachycardia. The use of a steerable catheter to locate the
      displaced His signal combined with the use of cryothermal energy allowed for the
      safe and effective treatment of this patient's tachycardia.

PMID- 20136862
TI  - An unusual cardiac defect in a patient with clinical features overlapping between
      cardiofaciocutaneous and Noonan syndromes.
AB  - It is important to recognize the possibility of a syndromic etiology of cardiac
      defects when dysmorphic features and other congenital defects are present. We
      report a patient who presented with atrial fibrillation and was found to have an
      abnormal mitral valve, congenital aneurysm of the left atrial appendage, and
      features consistent with both Cardiofaciocutaneous syndrome and Noonan syndrome.
      The congenital aneurysm of the left atrial appendage was a previously unreported
      cardiac presentation for either syndrome. Diagnostic considerations based upon
      his genotype and phenotype are discussed, along with his unique cardiac
      presentation and treatment.

PMID- 20136863
TI  - Hypoplastic right lung associated with right pulmonary vein stenosis and systemic
      collateral.
AB  - We present a case of a 6-month-old girl diagnosed as unilateral pulmonary vein
      stenosis (right inferior pulmonary vein) with dextroposition of the heart,
      hypoplastic right lung, hypoplastic right pulmonary artery, collateral from the
      descending aorta supplied right lower lung, connection between collateral and
      right pulmonary artery with retrograde flow from right pulmonary artery into main
      pulmonary artery, and right superior and middle pulmonary vein agenesis. A
      combined modality of imaging including chest film, echocardiography,
      multidetector computerized tomography, and the cardiac catheterization nicely
      demonstrated all of the unique and rare congenital abnormalities.

PMID- 20136864
TI  - Congenital heart disease and death case of swine flu.

PMID- 20136869
TI  - A conceptual analysis of the application of tradable permits to biodiversity
      conservation.
AB  - Tradable permits have been applied in many areas of environmental policy and may
      be a response to increasing calls for flexible conservation instruments that
      successfully conserve biodiversity while allowing for economic development. The
      idea behind applying tradable permits to conservation is that developers wishing
      to turn land to economic purposes, thereby destroying valuable habitat, may only
      do so if they submit a permit to the conservation agency showing that habitat of
      at least the equivalent ecological value is restored elsewhere. The developer
      himself does not need to carry out the restoration, but may buy a permit from a
      third party, thus allowing a market to emerge. Nevertheless, the application of
      tradable permits to biodiversity conservation is a complex issue because
      destroyed and restored habitats are likely to differ. There may be various trade
      offs between the ecological requirements that destroyed and restored habitats be
      as similar as possible, and the need for a certain level of market activity to
      have a functioning trading system. The success of tradable permits as an
      instrument for reconciling the conflicts between economic development and
      conservation depends on the existence of certain economic, institutional, and
      ecological preconditions, for example, a functioning institutional framework,
      sufficient expert knowledge, and adequate monitoring and enforcement mechanisms.

PMID- 20136870
TI  - On valuing information in adaptive-management models.
AB  - Active adaptive management looks at the benefit of using strategies that may be
      suboptimal in the near term but may provide additional information that will
      facilitate better management in the future. In many adaptive-management problems
      that have been studied, the optimal active and passive policies (accounting for
      learning when designing policies and designing policy on the basis of current
      best information, respectively) are very similar. This seems paradoxical; when
      faced with uncertainty about the best course of action, managers should spend
      very little effort on actively designing programs to learn about the system they
      are managing. We considered two possible reasons why active and passive adaptive
      solutions are often similar. First, the benefits of learning are often confined
      to the particular case study in the modeled scenario, whereas in reality
      information gained from local studies is often applied more broadly. Second,
      management objectives that incorporate the variance of an estimate may place
      greater emphasis on learning than more commonly used objectives that aim to
      maximize an expected value. We explored these issues in a case study of Merri
      Creek, Melbourne, Australia, in which the aim was to choose between two options
      for revegetation. We explicitly incorporated monitoring costs in the model. The
      value of the terminal rewards and the choice of objective both influenced the
      difference between active and passive adaptive solutions. Explicitly considering
      the cost of monitoring provided a different perspective on how the terminal
      reward and management objective affected learning. The states for which it was
      optimal to monitor did not always coincide with the states in which active and
      passive adaptive management differed. Our results emphasize that spending
      resources on monitoring is only optimal when the expected benefits of the options
      being considered are similar and when the pay-off for learning about their
      benefits is large.

PMID- 20136871
TI  - Safeguarding biodiversity and ecosystem services in the Little Karoo, South
      Africa.
AB  - Global declines in biodiversity and the widespread degradation of ecosystem
      services have led to urgent calls to safeguard both. Responses to this urgency
      include calls to integrate the needs of ecosystem services and biodiversity into
      the design of conservation interventions. The benefits of such integration are
      purported to include improvements in the justification and resources available
      for these interventions. Nevertheless, additional costs and potential trade-offs
      remain poorly understood in the design of interventions that seek to conserve
      biodiversity and ecosystem services. We sought to investigate the synergies and
      trade-offs in safeguarding ecosystem services and biodiversity in South Africa's
      Little Karoo. We used data on three ecosystem services--carbon storage, water
      recharge, and fodder provision--and data on biodiversity to examine several
      conservation planning scenarios. First, we investigated the amount of each
      ecosystem service captured incidentally by a conservation plan to meet targets
      for biodiversity only while minimizing opportunity costs. We then examined the
      costs of adding targets for ecosystem services into this conservation plan.
      Finally, we explored trade-offs between biodiversity and ecosystem service
      targets at a fixed cost. At least 30% of each ecosystem service was captured
      incidentally when all of biodiversity targets were met. By including data on
      ecosystem services, we increased the amount of services captured by at least 20%
      for all three services without additional costs. When biodiversity targets were
      reduced by 8%, an extra 40% of fodder provision and water recharge were obtained
      and 58% of carbon could be captured for the same cost. The opportunity cost (in
      terms of forgone production) of safeguarding 100% of the biodiversity targets was
      about US$500 million. Our results showed that with a small decrease in
      biodiversity target achievement, substantial gains for the conservation of
      ecosystem services can be achieved within our biodiversity priority areas for no
      extra cost.

PMID- 20136872
TI  - The role of landowners in jaguar conservation in Sonora, Mexico.
AB  - The northernmost known breeding population of jaguars occurs in the municipality
      of Nacori Chico, Sonora, Mexico about 270 km from the United States-Mexico border
      and may be the source from which jaguars sighted in the United States dispersed.
      Since 1999 at least 11 jaguars (Panthera onca) had been illegally killed in the
      area due to predator control programs. We initiated a jaguar landowner-based
      conservation plan in 2004. The eight participating landowners agreed to suspend
      predator control programs targeting jaguars and pumas (Puma concolor) only if
      cattle losses were compensated. A private outfitter, with the consent of
      landowners, initiated white-tailed deer (Odocoileus virginianus) hunts in 2004
      and agreed to pay the group of participating landowners US$1500 for every deer
      hunt permit sold. The funds paid to the landowners from deer hunts were
      sufficient to convince landowners to suspend all predator-control efforts of
      jaguars and pumas. The involvement of landowners in the jaguar conservation
      program in northeastern Sonora is a successful, private, wildlife-conservation
      initiative that provides an example for jaguar conservation efforts in northern
      Mexico.

PMID- 20136873
TI  - Birds as suppliers of seed dispersal in temperate ecosystems: conservation
      guidelines from real-world landscapes.
AB  - Seed dispersal by animals is considered a pivotal ecosystem function that drives
      plant-community dynamics in natural habitats and vegetation recovery in human
      altered landscapes. Nevertheless, there is a lack of suitable ecological
      knowledge to develop basic conservation and management guidelines for this
      ecosystem service. Essential questions, such as how well the abundance of
      frugivorous animals predicts seeding function in different ecosystems and how
      anthropogenic landscape heterogeneity conditions the role of dispersers, remain
      poorly answered. In three temperate ecosystems, we studied seed dispersal by
      frugivorous birds in landscape mosaics shaped by human disturbance. By applying a
      standardized design across systems, we related the frequency of occurrence of
      bird-dispersed seeds throughout the landscape to the abundance of birds, the
      habitat features, and the abundance of fleshy fruits. Abundance of frugivorous
      birds in itself predicted the occurrence of dispersed seeds throughout the
      landscape in all ecosystems studied. Even those landscape patches impoverished
      due to anthropogenic disturbance received some dispersed seeds when visited
      intensively by birds. Nonetheless, human-caused landscape degradation largely
      affected seed-deposition patterns by decreasing cover of woody vegetation or
      availability of fruit resources that attracted birds and promoted seed dispersal.
      The relative role of woody cover and fruit availability in seed dispersal by
      birds differed among ecosystems. Our results suggest that to manage seed
      dispersal for temperate ecosystem preservation or restoration one should consider
      abundance of frugivorous birds as a surrogate of landscape-scale seed dispersal
      and an indicator of patch quality for the dispersal function; woody cover and
      fruit resource availability as key landscape features that drive seedfall
      patterns; and birds as mobile links that connect landscape patches of different
      degrees of degradation and habitat quality via seed deposition.

PMID- 20136875
TI  - Formaldehyde-releasers in cosmetics: relationship to formaldehyde contact
      allergy. Part 1. Characterization, frequency and relevance of sensitization, and
      frequency of use in cosmetics.
AB  - In this part of a series of review articles on formaldehyde-releasers and their
      relationship to formaldehyde contact allergy, formaldehyde-releasers in cosmetics
      are discussed. In this first part of the article, key data are presented
      including frequency of sensitization and of their use in cosmetics. In Europe,
      low frequencies of sensitization have been observed to all releasers: 2-bromo-2
      nitropropane-1,3-diol 0.4-1.2%, diazolidinyl urea 0.5-1.4%, imidazolidinyl urea
      0.3-1.4%, quaternium-15 0.6-1.9% (for DMDM hydantoin no recent data are
      available). All releasers score (far) higher prevalences in the USA; the possible
      explanations for this are discussed. The relevance of positive patch test
      reactions has been insufficiently investigated. In the USA, approximately 20% of
      cosmetics and personal care products (stay-on products: 17%, rinse-off products
      27%) contain a formaldehyde-releaser. The use of quaternium-15 is decreasing. For
      Europe, there are no comparable recent data available. In the second part of the
      article, the patch test relationship of the releasers in cosmetics to
      formaldehyde contact allergy will be reviewed and it will be assessed whether
      products preserved with formaldehyde-releasers may contain enough free
      formaldehyde to pose a threat to individuals who have contact allergy to
      formaldehyde.

PMID- 20136876
TI  - Formaldehyde-releasers in cosmetics: relationship to formaldehyde contact
      allergy. Part 2. Patch test relationship to formaldehyde contact allergy,
      experimental provocation tests, amount of formaldehyde released, and assessment
      of risk to consumers allergic to formaldehyde.
AB  - This is the second part of an article on formaldehyde-releasers in cosmetics. The
      patch test relationship between the releasers in cosmetics to formaldehyde
      contact allergy is reviewed and it is assessed whether products preserved with
      formaldehyde-releasers may contain enough free formaldehyde to pose a threat to
      individuals with contact allergy to formaldehyde. There is a clear relationship
      between positive patch test reactions to formaldehyde-releasers and formaldehyde
      contact allergy: 15% of all reactions to 2-bromo-2-nitropropane-1,3-diol and 40
      60% of the reactions to the other releasers are caused by a reaction to the
      formaldehyde in the test material. There is only fragmented data on the amount of
      free formaldehyde in cosmetics preserved with formaldehyde donors. However, all
      releasers (with the exception of 2-bromo-2-nitropropane-1,3-diol, for which
      adequate data are lacking) can, in the right circumstances of concentration and
      product composition, release >200 p.p.m. formaldehyde, which may result in
      allergic contact dermatitis. Whether this is actually the case in any particular
      product cannot be determined from the ingredient labelling. Therefore, we
      recommend advising patients allergic to formaldehyde to avoid leave-on cosmetics
      preserved with quaternium-15, diazolidinyl urea, DMDM hydantoin, or
      imidazolidinyl urea, acknowledging that many would tolerate some products.

PMID- 20136877
TI  - Linalool--a significant contact sensitizer after air exposure.
AB  - BACKGROUND: Linalool is a widely used fragrance terpene. Pure linalool is not
      allergenic or a very weak allergen, but autoxidizes on air exposure and the
      oxidation products can cause contact allergy. Oxidized (ox.) linalool has
      previously been patch tested at a concentration of 2.0% in petrolatum (pet.) in
      1511 patients, and 1.3% positive patch test reactions were observed. OBJECTIVE:
      To investigate the optimal patch test concentration for detection of contact
      allergy to ox. linalool. METHODS: Four concentrations of ox. linalool (2.0%,
      4.0%, 6.0%, 11.0% pet.) were tested in 3418 consecutive dermatitis patients.
      RESULTS: Ox. linalool 2.0%, 4.0%, 6.0%, and 11.0% pet. detected positive patch
      test reactions in 0.83%, 3.2%, 5.3%, and 7.2% of the tested patients,
      respectively. The doubtful reactions increased with rising concentrations but
      relatively less, giving 5.1%, 6.4%, and 7.3% doubtful reactions, respectively,
      for ox. linalool 4.0%, 6.0%, and 11.0% pet. Few irritative reactions were seen.
      CONCLUSIONS: Raising the patch test concentration for ox. linalool gave a better
      detection of contact allergy, as many as 5-7% positive patch test reactions were
      detected. We suggest a patch test concentration of ox. linalool 6.0% pet. for
      future patch testing, giving a dose per unit area of 2.4 mg/cm(2) when 20 mg test
      substance is tested in small Finn Chambers.

PMID- 20136878
TI  - Contact and photocontact sensitization in chronic actinic dermatitis: a changing
      picture.
AB  - BACKGROUND: Patients with chronic actinic dermatitis (CAD) frequently have
      positive patch or photopatch tests. In our previous study (period 1987-1992), the
      most prominent contact allergen was the sesquiterpene lactone mix (36% of
      patients with CAD). OBJECTIVE: To assess whether contact allergy profiles in CAD
      patients between 2000 and 2005 have changed in respect to our previous data (1987
      1992). PATIENTS AND METHODS: Fifty CAD patient records from 2000 to 2005 for
      patch and photopatch testing were retrospectively analysed and data were compared
      with that from 86 patients seen between 1987 and 1992. RESULTS: Thirty-two (64%)
      and 64 (74%) patients had positive patch or photopatch tests in 2000-2005 and
      1987-1992, respectively. The allergen profile has altered. A decline in
      sesquiterpene lactone mix positive reactions was noted: 29 (36%) patients were
      positive in 1987-1992 and 10 (20%) patients in 2000-2005, but this was not
      significant (P = 0.08). Reactions to non-fragrance consumer allergens (i.e. p
      phenylenediamine and preservatives) had risen from 7 reactions (1987-1992) to 21
      reactions in 13 individuals (2000-2005) (P < 0.001). Of these allergens, p
      phenylenediamine was the most common (12%; P = 0.004). CONCLUSIONS: A significant
      rise in positive patch tests to non-fragrance consumer allergens, particularly p
      phenylenediamine, was seen in CAD patients in 2000-2005. We speculate this
      alteration of allergen profile may be partly due to changes in exposure patterns.

PMID- 20136879
TI  - Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS).
AB  - BACKGROUND: In some patterns of cutaneous adverse drug reactions, and depending
      on the culprit drug, patch testing has been helpful in confirming its cause. Its
      value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been
      established in a large cohort of patients. OBJECTIVE: The aim of the present
      study is to evaluate the safety and usefulness of patch testing in DRESS.
      PATIENTS/METHODS: Between January 1998 and December 2008, we studied 56 patients
      with DRESS induced by antiepileptic agents in 33 patients (59%), allopurinol in
      19 (34%) and sulfasalazine, cotrimoxazole, tenoxicam, and amoxicillin in 1
      patient each (7%). RESULTS: A positive patch test reaction was observed in 18
      patients (32.1%), of which 17 were with antiepileptics and 1 with tenoxicam. In
      the antiepileptic group, carbamazepine alone was responsible for 13 of 17
      positive reactions (76.5%). Patch tests with allopurinol and its metabolite were
      negative in all cases attributed to this drug. CONCLUSIONS: In this study, patch
      testing was a safe and useful method in confirming the culprit drug in DRESS
      induced by antiepileptic drugs, whereas it had no value in DRESS induced by
      allopurinol. The pathogenesis of DRESS is not yet entirely clarified, but
      positive patch tests suggest a drug-dependent delayed hypersensitivity mechanism.

PMID- 20136880
TI  - Contact dermatitis due to Centella asiatica.

PMID- 20136881
TI  - Contact allergy to epoxy resins--a 10-year study.

PMID- 20136882
TI  - Concomitant contact allergy to methylchloroisothiazolinone/methylisothiazolinone
      and formaldehyde-releasing preservatives.

PMID- 20136883
TI  - Allergic contact dermatitis from aluminium in deodorants.

PMID- 20136884
TI  - Vermilion hypopigmentation at an unusual site.

PMID- 20136885
TI  - Occupational contact dermatitis from ninhydrin in a police officer.

PMID- 20136886
TI  - Pigmented contact cheilitis: from green tea?

PMID- 20136887
TI  - Allergic contact dermatitis associated with mugwort (Artemisia vulgaris).

PMID- 20136888
TI  - Pigmented contact dermatitis due to kojic acid. A paradoxical side effect of a
      skin lightener.

PMID- 20136889
TI  - Allergic contact dermatitis to natural resin rare among gum rosin extractors?

PMID- 20136890
TI  - The epidemiology of hand eczema in the general population--prevalence and main
      findings.
AB  - Numerous studies have investigated the prevalence and risk factors of hand eczema
      in the general population. These studies are of high value as they tend to be
      less biased than studies using clinical populations and as they are important for
      healthcare decision makers when they allocate resources. This study aimed to
      review the epidemiology of hand eczema in the general population. Literature was
      examined using Pubmed-Medline, Biosis, Science Citation Index, and dermatology
      text books. On the basis of studies performed between 1964 and 2007, the point
      prevalence of hand eczema was around 4%, the 1-year prevalence nearly 10%,
      whereas the lifetime prevalence reached 15%. Based on seven studies, the median
      incidence rate of hand eczema was 5.5 cases/1000 person-years (women = 9.6 and
      men = 4.0). A high incidence rate was associated with female sex, contact
      allergy, atopic dermatitis, and wet work. Atopic dermatitis was the single most
      important risk factor for hand eczema. Hand eczema resulted in medical
      consultations in 70%, sick leave (> 7 days) in about 20%, and job change in about
      10%. Mean sick time was longer among those with allergic hand eczema than those
      with atopic and irritant hand eczema. Moderate to severe extension of hand eczema
      was the strongest risk factor for persistence of hand eczema. Other risk factors
      included early onset of hand eczema and childhood eczema. The aetiology of hand
      eczema is multifactorial and includes environmental as well as genetic factors.
      Future studies should focus on unresolved areas of hand eczema, for example,
      genetic predisposition.

PMID- 20136891
TI  - Sensitization to dimethyl fumarate with multiple concurrent patch test reactions.
AB  - BACKGROUND: Chairs and sofas imported from China to Europe were shown to contain
      dimethyl fumarate (DMF), a sensitizing, volatile chemical. Many of the sensitized
      patients also had positive patch test reactions to acrylates. OBJECTIVES: To
      analyse the occurrence and strength of DMF sensitization and the appearance of
      concomitant reactions. METHODS: Patch testing with DMF in concentrations of 0.1
      0.00001% was carried out in 37 patients. Diethyl fumarate (DEF), diethyl maleate
      (DEM), dimethyl maleate (DMM), ethyl acrylate (EA), methyl acrylate (MA), and
      methyl methacrylate (MMA) were also tested with a dilution series at equimolar
      concentrations. RESULTS: The lowest concentration of DMF eliciting a reaction
      varied between 0.0001% and 0.1% and all but four patients reacted concurrently to
      DEF. DEM elicited positive patch test reactions in 21/37 patients and DMM
      reactions were seen in all 9 patients tested. EA elicited positive reactions in
      13/37 patients and a positive MA reaction was seen in 7/37 patients, 2 of whom
      also reacted to MMA. CONCLUSIONS: The strength of the sensitization to DMF showed
      variation and concurrent reactions were common. Concurrent reactions to
      (meth)acrylates were seen in patients, who reacted to lower (0.001% or less) DMF
      concentration probably elicited by cross-reactivity.

PMID- 20136892
TI  - Active sensitization and contact allergy to methyl 2-octynoate.
AB  - BACKGROUND: Methyl 2-octynoate is a synthetic fragrance which was first described
      to have sensitizing properties in 1935. It is one of the 26 fragrances to be
      labelled on the ingredient list according to current European cosmetics
      regulation. OBJECTIVES: To report the experience with patch testing with methyl 2
      octynoate 1% and 2% in pet. METHODS: 230 eczema patients were consecutively patch
      tested with 1% methyl 2-octynoate at department of Dermato-allergology Gentofte
      Hospital, Denmark and 120 eczema patients were consecutively patch tested with 2%
      M2O in Finn Chambers at the Department de Dermatologie, CHU Saint Jacques,
      France. RESULTS: Three cases of active sensitization were observed. 2 (0.87%) of
      the 230 Danish subjects tested with 1% in pet. and of the 120 French subjects
      patch tested with 2% in pet. 1 (0.83%). There was no statistical difference in
      active sensitization between the two groups (P = 0.72). Allergic contact
      dermatitis was observed in two patients (1.67%) in the French group and none in
      the Danish group. CONCLUSION: Contact allergy to methyl 2-octynoate was
      frequently seen when patch testing with 2% in pet. However, active sensitization
      was also observed, when patch testing with concentrations of 1% and 2% methyl 2
      octynoate. The patch test concentration should be below 1% in pet., but a safe
      concentration remains to be defined.

PMID- 20136893
TI  - Temporal trends of preservative allergy in Denmark (1985-2008).
AB  - BACKGROUND: Most cosmetics and industrial products contain preservatives.
      Preservative allergy is common and, historically, changing contact allergy
      epidemics caused by preservatives have been observed. In 1997, Alan Dillarstone
      predicted a stable development of preservative allergy following mandatory
      ingredient labelling on cosmetic products. OBJECTIVES: To investigate the
      development in the prevalence of preservative allergy in Denmark over a 24-year
      period (1985-2008) and to challenge the prediction made by Dillarstone.
      PATIENTS/METHODS: A retrospective analysis of patch test data was performed (n =
      18179). Comparisons were made using a chi(2) test. Logistic regression analyses
      were used to test for associations. RESULTS: The development of preservative
      allergy mirrored those of other European patch test centres. The development was
      not dependent on sex or age group. The prevalence was higher among women and
      those aged 41-60 years. Formaldehyde allergy was persistently prevalent over the
      study years. The overall prevalence of preservative allergy increased
      significantly (P(trend) = 0.001), mainly because of patch testing with additional
      preservatives in recent years. CONCLUSIONS: Dillarstone's prediction was
      confirmed as the prevalence of contact allergy to individual preservatives
      remained relatively stable. However, the overall burden of preservative allergy
      seemed to increase. Introduction of new preservatives may add to the burden of
      contact allergy.

PMID- 20136894
TI  - Comparison of human skin irritation patch test data with in vitro skin irritation
      assays and animal data.
AB  - BACKGROUND: Efforts to replace the rabbit skin irritation test have been underway
      for many years, encouraged by the EU Cosmetics Directive and REACH. Recently
      various in vitro tests have been developed, evaluated and validated. OBJECTIVE: A
      key difficulty in confirming the validity of in vitro methods is that animal data
      are scarce and of limited utility for prediction of human effects, which
      adversely impacts their acceptance. This study examines whether in vivo or in
      vitro data most accurately predicted human effects. METHODS: Using the 4-hr human
      patch test (HPT) we examined a number of chemicals whose EU classification of
      skin irritancy is known to be borderline, or where in vitro methods provided
      conflicting results. RESULTS: Of the 16 chemicals classified as irritants in the
      rabbit, only five substances were found to be significantly irritating to human
      skin. Concordance of the rabbit test with the 4-hr HPT was only 56%, whereas
      concordance of human epidermis models with human data was 76% (EpiDerm) and 70%
      (EPISKIN). CONCLUSIONS: The results confirm observations that rabbits overpredict
      skin effects in humans. Therefore, when validating in vitro methods, all
      available information, including human data, should be taken into account before
      making conclusions about their predictive capacity.

PMID- 20136895
TI  - Lymphomatoid photocontact dermatitis to benzydamine hydrochloride.

PMID- 20136896
TI  - An unusual case of cell phone dermatitis.

PMID- 20136897
TI  - Allergic contact dermatitis to decyl glucoside in Tinosorb M.

PMID- 20136898
TI  - Peristomal allergic contact dermatitis to stoma-adhesive paste containing
      monobutyl ester/maleic acid of polymethylvinylether (Gantrez 425) but not to
      Isopropyl ester/maleic anhydride of polymethylvinylether (Gantrez 335).

PMID- 20136899
TI  - Allergic contact dermatitis to dimethyl fumarate in footwear.

PMID- 20136900
TI  - Occupational allergic contact dermatitis to olanzapine.

PMID- 20136901
TI  - Occupational allergic contact dermatitis to HBTU [(o-benzotriazole-10yl)
      N,N,N',N,-tetramethyluronium hexafluorophosphate].

PMID- 20136902
TI  - Allergy 'sucks': leeches may also be harmful.

PMID- 20136903
TI  - Photoprotection and vitamin D.

PMID- 20136904
TI  - Vitamin D metabolism.
AB  - Irradiation of human skin with ultraviolet B (280-320 nm) initiates the
      photochemical conversion of 7-dehydrocholesterol via previtamin D3 to vitamin D3.
      Vitamin D3 needs for its activation two hydroxylation steps in the liver and
      kidney. The final product, hormonally active 1alpha,25-dihydroxyvitamin D3
      (calcitriol), arrives via the circulation to its target tissues and acts in a
      genomic or nongenomic manner. It has been found that human skin irradiated with
      ultraviolet B also is able to produce calcitriol in substantial amounts. This
      cutaneous vitamin D3 pathway is unique and, most likely, of considerable
      relevance for healthy and diseased skin. It is well known that topical
      application of calcitriol and its analogs can improve hyperproliferative skin
      diseases. Some studies have convincingly demonstrated that calcitriol and other
      vitamin D analogs may also be used for the treatment of immunological,
      inflammatory, and infectious skin diseases. More recently, it has been found that
      calcitriol or vitamin D analogs have photoprotective effects and can reduce UV
      induced deoxyribonucleic acid damage.

PMID- 20136905
TI  - Vitamin D and innate immunity.
AB  - Vitamin D's role in bone health has been well established. Recently, studies have
      identified additional roles of vitamin D in the immune system, cardiovascular
      system, and cancer prevention. The effect of vitamin D on the immune system is
      particularly relevant to the dermatologist in that it has implications for atopic
      dermatitis, psoriasis, and skin cancer. However, there is much disagreement on a
      dose of vitamin D that is both safe and effective as both ultraviolet exposure
      and certain vitamin D-rich foods come with unwanted consequences. This review
      aims to update the dermatologist on the roles of vitamin D in the immune system,
      the safety and dose of different sources, and risk factors for vitamin D
      deficiency that may necessitate supplementation. Immune consequences of vitamin D
      status represent one additional aspect that illustrates how guidelines for
      supplementation are needed and will only be useful clinically if they are
      presented in context with validated controlled clinical trials.

PMID- 20136906
TI  - Health effects of vitamin D.
AB  - Increasing data suggest that many or most adults in the United States and Europe
      would benefit from vitamin D supplements. This review summarizes the benefits of
      vitamin D with the strongest evidence today from randomized controlled trials for
      fall and fracture prevention. Beyond fall and fracture prevention, vitamin D may
      also reduce overall morbidity by multiple mechanisms. Prospective epidemiological
      studies supported by strong mechanistic evidence suggest a reduction of
      cardiovascular disease (incident hypertension and cardiovascular mortality) and
      colorectal cancer, extending to weaker evidence on immune-modulatory and anti
      inflammatory benefits of vitamin D.

PMID- 20136907
TI  - Photoprotection: a review of the current and future technologies.
AB  - Exposure to ultraviolet (UV) radiation is associated with a variety of harmful
      effects ranging from photoaging to skin cancer. UVB (290 to 320 nm) directly
      damages the cellular DNA leading to the formation of the 6-4 cyclobutane
      pyrimidine dimmers, and UVA (320 to 400 nm) indirectly damages the DNA via the
      production of oxygen radical species. In this review, we focused on the
      technological and scientific aspects of photoprotection using sunglasses and
      clothing while attempting to dispel some of the misconceptions. In addition to
      the basic knowledge relating to sunscreens, we reviewed the current guidelines
      for testing and labeling UVA protection around the world, controversies
      associated with nanoparticles, and future sunscreens actives waiting for the Food
      and Drug Administration approval. Lastly, we reviewed alternative agents, such as
      antioxidants, that can be used to supplement and augment photoprotection provided
      by sunscreens.

PMID- 20136908
TI  - Effects of ambient sunlight and photoprotection on vitamin D status.
AB  - Ultraviolet B radiation exposure is responsible for the majority of natural
      vitamin D stores in humans. The physiologic role of vitamin D in health and
      disease is continually expanding, and at the same time the population that is
      vitamin D deficient is increasing. The environmental characteristics and personal
      physical traits that contribute to vitamin D3 synthesis from sun exposure are
      discussed, and the effects of photoprotection on vitamin D status are examined.
      It is concluded that sunscreen, in the manner used by the general public, does
      not cause vitamin D insufficiency. Implementing guidelines suggesting sun
      exposure duration for sufficient vitamin D3 production is limited by the complex
      interaction of contributory factors, and no recommendation can be made that is
      both safe and accurate enough for general public usage.

PMID- 20136909
TI  - Tanning beds, skin cancer, and vitamin D: An examination of the scientific
      evidence and public health implications.
AB  - Indoor tanning has become increasingly popular over the past decades, despite
      evidence of an increased risk of melanoma and, possibly, nonmelanoma skin cancer.
      Tanning bed proponents cite the health benefits of vitamin D to support indoor
      tanning, including concerns that reduced vitamin D levels or certain vitamin D
      receptor polymorphisms may be associated with increased incidence of various
      cancers, including cutaneous melanoma. However, most tanning devices primarily
      emit ultraviolet A, which is relatively ineffective in stimulating vitamin D
      synthesis. Health benefits can be fully dissociated from the ultraviolet exposure
      risks with vitamin D supplementation, although optimal levels remain to be
      established. Indoor tanning represents an avoidable risk factor for skin cancer,
      and education of the general public as well as the enactment and stricter
      enforcement of indoor tanning legislation are a public health imperative.

PMID- 20136910
TI  - UV-based therapy and vitamin D.
AB  - The ultraviolet (UV) light spectrum has long been known to induce biologic effect
      on the skin. For a large number of cutaneous disorders, phototherapy and
      photochemotherapy are effective therapeutic options with excellent safety
      profiles and well-documented side effects. Despite their ease of administration
      and benefits, phototherapeutic treatment modalities require appropriate space for
      the equipment, trained staff, and patient education prior to initiating
      treatment. However, when the initial barriers to treatment can be overcome, UV
      therapy can offer patients significant relief from their cutaneous disease.
      Furthermore, UVB-based phototherapy can produce significant alteration to vitamin
      D levels. With the recent research implicating association of low vitamin D
      levels with a variety of health conditions, whether patients receiving
      phototherapy or, more specifically, those getting vitamin D supplement may be
      protected from these diseases remains to be established.

PMID- 20136911
TI  - Therapeutic Hotline: Recommendations on photoprotection and vitamin D.
AB  - Interest in the health benefits of vitamin D continues to increase and is at the
      forefront of much research and debate. Insufficient vitamin D levels have been
      linked in epidemiologic studies to decreased physical performance, cardiac
      health, autoimmune disease, neurologic disorders, colorectal and breast cancers,
      and total mortality. Consequently, health authorities are reviewing the most
      recent available data and updated recommendations on optimal vitamin D levels are
      pending. Daily intake of 1000 international units (IU) of vitamin D for adults
      and 400 IU of vitamin D for children may be appropriate for patients protecting
      their skin from UV radiation and can be safely obtained from diet and/or dietary
      supplementation. Patients should be counseled on sun protection regimens to
      prevent unprotected sun exposure and discouraged from using artificial tanning
      devices. As available information on vitamin D and its associated health benefits
      evolves, and as new evidence emerges, updated recommendations are sure to follow.

PMID- 20136912
TI  - Therapeutic Hotline: Facial skin rejuvenation in a patient treated with
      photodynamic therapy for actinic keratosis.
AB  - The aim of the most used treatments of actinic keratoses (AKs) is to avoid the
      conversion into invasive squamous cell carcinoma through the destruction of the
      lesion; a lot of therapeutic modalities (imiquimod, 5-fluorouracil,
      electrosurgery with curettage, cryosurgery) are effective and safe in this field,
      but not many can do it with excellent cosmetic results like treatment with
      photodynamic therapy (PDT). We have treated with this technique an old patient,
      whose AK was resistant to other treatments; the most interesting feature of our
      case comes from the esthetic effects of the PDT employing a methyl-ester of 5
      aminolevulinic acid as topical photosensitizer. This kind of therapy has removed
      not only the lesion but also the photoaging manifestations like the wrinkles and
      the ugly lines, leaving a smooth skin, as we have proved with 3D-profilometry
      technique.

PMID- 20136913
TI  - Therapeutic Hotline: Cysteinyl leukotriene receptor antagonist montelukast in the
      treatment of atopic dermatitis.
AB  - Leukotrienes are potent proinflammatory mediators derived from arachidonic acid
      through the 5-lipoxygenase pathway. Experimental data suggest a role for
      cysteinyl leukotrienes in the pathogenesis of atopy giving a rationale for its
      use in asthma, allergic rhinitis, and chronic urticaria management. A few
      clinical observations and small trials suggest that montelukast may be used in an
      adjunctive manner as an effective therapeutic option for all age categories
      affected by moderate-to-severe atopic dermatitis. Our own observations proved
      that montelukast as a prospective corticosteroid-sparing option in the complex
      therapeutic strategy of corticosteroid-dependent atopic dermatitis patients, even
      in the severe erythrodermic cases.

PMID- 20136914
TI  - Therapeutic Hotline: Topical glycopyrrolate: a successful treatment for
      craniofacial hyperhidrosis and eccrine hidrocystomas.
AB  - Eccrine hidrocystoma is a benign tumor derived from eccrine sudoriparous glands.
      Most eccrine hidrocystomas are solitary and asymptomatic lesions. Multiple
      hidrocystomas are unusual and have been associated with Graves' disease,
      Parkinson's disease, and idiopathic craniofacial hyperhidrosis. This report
      describes the successful treatment of multiple center facial eccrine
      hidrocystomas associated with craniofacial hyperhidrosis with 0.5% glycopyrrolate
      aqueous solution applied locally for 1 week. The present authors obtained a very
      significant improvement without leaving any trace of clinical examination.
      Multiple eccrine hidrocystomas are a rare condition and, to date, no effective
      treatment has been reported. Topical glycopyrrolate is a very good first-line
      treatment option.

PMID- 20136915
TI  - Unusual presentation of tuberculosis in an infliximab-treated patient--which is
      the correct TB screening before starting a biologic?
AB  - Infliximab is an anti-TNFalpha chimeric monoclonal antibody, commonly used in the
      treatment of moderate to severe psoriasis. TNFalpha is a pro-inflammatory
      cytokine which play a key role in host defense from infections by intracellular
      bacteria, such as Listeria monocytogenes, Histoplasma Capsulatum and especially
      Mycobacterium Tuberculosis. Infliximab therapy increases the risk of tuberculosis
      due mainly to the reactivation of latent TB infection (LTBI) and, therefore, it
      is mandatory to screen patients for LTBI prior to starting a treatment with anti
      TNFalpha agents. We report the case of a psoriatic patient, who, despite a
      negative screening for infection by M. tuberculosis including both tuberculin
      skin test (TST) and chest X-ray, developed after 4 months of infliximab
      treatment, a severe pulmonary, lymphnodal and intestinal tuberculosis during
      infliximab treatment.

PMID- 20136916
TI  - Correlation between BMI and PASI in patients affected by moderate to severe
      psoriasis undergoing biological therapy.
AB  - Obesity is common in psoriatic patients, and it has been shown to be important
      for many aspects of the condition. In particular, low-calorie diets can improve
      the symptoms and response to treatment in pustular psoriasis. The present study
      investigates the influence of body-weight alteration on the disease's clinical
      manifestations in moderate to severe psoriasis patients treated with biological
      drugs. Finally, the influence of a caloric restriction was assessed. This
      observational transversal study enrolled 33 patients attending our Severe
      Psoriasis Outpatient Clinic, who were treated with biological drugs. Body Mass
      Index (BMI) was used as a diagnostic indicator of being overweight and of
      obesity. Waist circumference was also measured. Body weight and Psoriasis Area
      Severity Index (PASI) index were measured at follow-up visits at 4 and 8 months.
      Nonparametric test of Mann-Whitney was used to detect the differences between
      patient groups. Fisher's exact test was performed to evaluate the different
      results depending on the therapeutic changes of BMI. There was a strong
      prevalence of overweight-obese individuals in the group with a mean BMI of 30.59
      +/- 6.94. Waist circumference was also above normal in the majority of the
      patients. Obese patients had a PASI index higher than the average of the whole
      group (25.03 +/- 12.43), with grade III obese patients having an average PASI of
      44 +/- 3.37. At the first and second follow-ups, patients who put on weight did
      not achieve PASI 50; patients who had a stable weight presented variable response
      to treatment, while patients who decreased their weight achieved PASI 90 or PASI
      75 even when not responding at the first. Further studies are needed to
      understand if the poor response observed in heavier patients is due to biological
      drugs pharmacokinetics or because therapy should be BMI based rather than
      administered in fixed doses, posing then an ethical consideration.

PMID- 20136917
TI  - Eccrine syringofibroadenoma radiation treatment of an unusual presentation.
AB  - Benign skin diseases have seldom been treated with radiotherapy, unless resistant
      to other treatments. Eccrine syringofibroadenoma (ESFA) is a rare benign eccrine
      tumor. ESFA very rarely presents bilateral lesions, and seldom a nonsurgical
      treatment has been proposed. An exceptional case of bilateral ESFA of the foot is
      presented; radiotherapy was effective in treating both lesions with good cosmetic
      results.

PMID- 20136918
TI  - Treatment of disseminated granuloma annulare with allopurinol: case report.
AB  - Granuloma annulare (GA) is a rare disease characterized by granulomatous
      inflammation of the dermis. A variant form of the disease, disseminated granuloma
      annulare (DGA), can be observed in about 15% of affected patients. Localized GA
      is likely to resolve spontaneously within months or a few years, whereas DGA can
      persist for decades. Various therapies have been suggested in these cases, but
      none of them has been demonstrated to be consistently efficacious. Allopurinol
      has been successfully used in granulomatous diseases such as sarcoidosis or
      reactions to polymethylmethacrylate spheres; therefore, we decided to evaluate
      the possible efficacy of this drug in three patients with long-lasting, therapy
      resistant DGA.

PMID- 20136919
TI  - Topical Boswellic acids for treatment of photoaged skin.
AB  - Boswellic acids (BAs) are pentacyclic triterpenes extracted from the gum resins
      of the tropical tree Boswellia serrata. They are orally administered in
      traditional Indian medicine for the treatment of several inflammatory disease and
      cancer because of their anti-inflammatory and immunomodulatory activities as well
      as stimulatory effects on fibroblasts. The present authors have investigated
      efficacy, tolerability, and safety of a base cream containing 0.5% BAs in the
      treatment of clinical manifestations of photoaging of facial skin with a
      randomized, double-blind, placebo-controlled, split-face study. Fifteen female
      volunteers applied the creams with or without BAs on the half sides of the face
      once daily for 30 days. Significant improvements of the Dover's global score for
      photoaging, tactile roughness, and fine lines, as well as, with noninvasive
      diagnostic techniques, an increase of elasticity, a decrease of sebum excretion,
      and a change of echographic parameters were observed with topical BAs in
      comparison with placebo. The treatment was always well tolerated without adverse
      effects. The present findings seem to indicate that topical application of BAs
      may represent a suitable treatment option for selected features of skin
      photoaging.

PMID- 20136920
TI  - Combined treatment of Favre-Racouchot syndrome with a superpulsed carbon dioxide
      laser: report of 50 cases.
AB  - Nodular elastosis with cysts and comedones also known as Favre-Racouchot syndrome
      frequently occurs on actinically damaged skin of middle-aged or elderly Caucasian
      subjects. The disease usually affects simmetrically the skin mainly around the
      orbits. Treatment in the past has not been entirely satisfactory. Treatment of 50
      patients with a superpulsed carbon dioxide laser in order to vaporize epidermis
      followed by extraction of cystic and comedonic material using soft pressure with
      a pair of forceps. Laser treatment was performed without previous topical or
      intralesional anesthetics because no pain was reported using the described laser
      parameters. Our combined therapeutic approach was safe and effective in all the
      patients, guaranteeing an excellent cosmetic result. The combined technique
      assures clinical efficacy, rapid recovery, and the possibility of repeated laser
      application without anesthesia. On the basis of our results, we recommend the
      novel combined modality in the treatment of Favre-Racouchot syndrome.

PMID- 20136921
TI  - Cost-effectiveness analysis of TNF-alpha blockers for the treatment of chronic
      plaque psoriasis in the perspective of the Italian health-care system.
AB  - The cost-effectiveness of biological treatments for psoriasis is not well
      determined and may vary from country to country. The objectives of this study was
      to perform a cost-effectiveness analysis of infliximab compared with other anti
      tumor necrosis factor-alpha agents for the treatment of psoriasis in Italy. The
      incremental cost-effectiveness ratio per patients achieving at least 75%
      improvement in the psoriasis area and severity index assessed over 24- and 48-50
      week periods was calculated. Efficacy data were drawn from randomized controlled
      trials when available or from open label studies. Considering patients achieving
      psoriasis area and severity index at week 24 and 48-50, infliximab was dominant
      (more effective and less costly) over etanercept given at 50 mg twice weekly. In
      contrast, infliximab was not dominant over etanercept at other dosages or over
      adalimumab. When considering the impact of therapy on quality of life at Week 12
      using the Dermatology Life Quality Index equal to zero, infliximab resulted more
      effective and less costly than etanercept. Therefore, infliximab seems to be cost
      effective in the therapy of psoriasis. Further cost-efficacy evaluations based on
      head-to-head trials are necessary to address health economic considerations.

PMID- 20136922
TI  - The contact principle and utilitarian moral judgments in young children.
AB  - In three experiments involving 207 preschoolers and 28 adults, we investigated
      the extent to which young children base moral judgments of actions aimed to
      protect others on utilitarian principles. When asked to judge the rightness of
      intervening to hurt one person in order to save five others, the large majority
      of children aged 3 to 5 years advocated intervention in contrast to another
      situation with the reverse cost/benefit ratio. This course of action was seen as
      acceptable by most children only when it did not require the agent to have
      physical contact with the victim and the victim's harm was intended to produce
      the greatest good for the greatest number. Overall, the children's responses were
      remarkably similar to those reported in adult studies. These findings document
      the extent to which some constraints on moral judgment are present in early human
      development.

PMID- 20136923
TI  - Touch attenuates infants' physiological reactivity to stress.
AB  - Animal studies demonstrate that maternal touch and contact regulate infant
      stress, and handling during periods of maternal deprivation attenuates the stress
      response. To measure the effects of touch on infant stress reactivity during
      simulated maternal deprivation, 53 dyads were tested in two paradigms: still-face
      (SF) and still-face with maternal touch (SF+T). Maternal and infant cortisol
      levels were sampled at baseline, reactivity, and recovery and mother's and
      infant's cardiac vagal tone were measured during the free play, still-face, and
      reunion episodes of the procedure. Cortisol reactivity was higher among infants
      in the SF condition and while cortisol decreased at recovery for infants in the
      SF+T, it further increased for those in the SF. Vagal tone showed a greater
      suppression when SF was not accompanied by maternal touch. Touch synchrony during
      free play was associated with higher infant vagal tone, whereas touch
      myssynchrony--maternal tactile stimulation while the infant gaze averts-
      correlated with higher maternal and infant cortisol. In humans, as in mammals,
      the provision of touch during moments of maternal unavailability reduces infants'
      physiological reactivity to stress.

PMID- 20136924
TI  - Sensori-motor experience leads to changes in visual processing in the developing
      brain.
AB  - Since Broca's studies on language processing, cortical functional specialization
      has been considered to be integral to efficient neural processing. A fundamental
      question in cognitive neuroscience concerns the type of learning that is required
      for functional specialization to develop. To address this issue with respect to
      the development of neural specialization for letters, we used functional magnetic
      resonance imaging (fMRI) to compare brain activation patterns in pre-school
      children before and after different letter-learning conditions: a sensori-motor
      group practised printing letters during the learning phase, while the control
      group practised visual recognition. Results demonstrated an overall left
      hemisphere bias for processing letters in these pre-literate participants, but,
      more interestingly, showed enhanced blood oxygen-level-dependent activation in
      the visual association cortex during letter perception only after sensori-motor
      (printing) learning. It is concluded that sensori-motor experience augments
      processing in the visual system of pre-school children. The change of activation
      in these neural circuits provides important evidence that 'learning-by-doing' can
      lay the foundation for, and potentially strengthen, the neural systems used for
      visual letter recognition.

PMID- 20136925
TI  - Spontaneous analog number representations in 3-year-old children.
AB  - When enumerating small sets of elements nonverbally, human infants often show a
      set-size limitation whereby they are unable to represent sets larger than three
      elements. This finding has been interpreted as evidence that infants
      spontaneously represent small numbers with an object-file system instead of an
      analog magnitude system (Feigenson, Dehaene & Spelke, 2004). In contrast, non
      human animals and adult humans have been shown to rely on analog magnitudes for
      representing both small and large numbers (Brannon & Terrace, 1998; Cantlon &
      Brannon, 2007; Cordes, Gelman, Gallistel & Whalen, 2001). Here we demonstrate
      that, like adults and non-human animals, children as young as 3 years of age
      spontaneously employ analog magnitude representations to enumerate both small and
      large sets. Moreover, we show that children spontaneously attend to numerical
      value in lieu of cumulative surface area. These findings provide evidence of
      young children's greater sensitivity to number relative to other quantities and
      demonstrate continuity in the process they spontaneously recruit to judge small
      and large values.

PMID- 20136926
TI  - The development of spontaneous gender stereotyping in childhood: relations to
      stereotype knowledge and stereotype flexibility.
AB  - The development of spontaneous gender stereotyping in children was investigated
      using the newly developed Action Interference Paradigm (AIP). This task consists
      of assigning gender-stereotypical toys as quickly as possible to boys and girls
      in either a stereotype-congruent or a stereotype-incongruent manner. A pilot
      study with 38 children (mean age 5.1 years) provided evidence for spontaneous
      gender stereotyping in the AIP, which was reflected in higher latencies for
      stereotype-incongruent compared with stereotype-congruent toy assignments. The
      main study, with 66 children (aged 5, 8 and 11 years), compared the development
      of spontaneous stereotyping with established measures of stereotype flexibility
      and stereotype knowledge. Stereotype flexibility showed a strong increase from
      age 5 to 11. In contrast, stereotype knowledge and spontaneous stereotyping
      remained stable at high levels. The results provide evidence for a dissociation
      between stereotype flexibility and spontaneous stereotyping, suggesting that
      spontaneous stereotyping may be more closely related to stereotype knowledge than
      to stereotype flexibility.

PMID- 20136927
TI  - Representing intentions in self and other: studies of autism and typical
      development.
AB  - Two experiments were conducted to explore the extent to which individuals with
      Autism Spectrum Disorder (ASD), as well as young typically developing (TD)
      children, are explicitly aware of their own and others' intentions. In Experiment
      1, participants with ASD were significantly less likely than age- and ability
      matched comparison participants to correctly recognize their own knee-jerk reflex
      movements as unintentional. Performance on this knee-jerk task was associated
      with performance on measures of false belief understanding, independent of age
      and verbal ability, in both participants with ASD and TD children. In Experiment
      2, participants with ASD were significantly less able than comparison
      participants to correctly recognize their own or another person's mistaken
      actions as unintended, in a 'Transparent Intentions' task (Russell & Hill, 2001;
      Russell, Hill & Franco, 2001). Performance on aspects of the Transparent
      Intentions task was associated with performance on measures of false belief
      understanding, independent of age and verbal ability, in both participants with
      ASD and TD children. This study suggests that individuals with ASD have a
      diminished awareness of their own and others' intentions and that this diminution
      is associated with other impairments in theory of mind.

PMID- 20136928
TI  - Intuitions about gravity and solidity in great apes: the tubes task.
AB  - We investigated whether great apes, like human infants, monkeys and dogs, are
      subject to a strong gravity bias when tested with the tubes task, and--in case of
      mastery--what the source of competence on the tubes task is. We presented 22 apes
      with three versions of the tubes task, in which an object is dropped down a tube
      connected to one of three potential hiding places and the subject is required to
      locate the object. In two versions, apes were confronted with a causal tube that
      varied in the amount of perceptual information it provided (i.e. presence or
      absence of acoustic cues). The third version was a non-causal adaptation of the
      task in which a painted line 'connected' dropping and hiding places. Results
      indicate that apes neither have a reliable gravity bias when tested with the
      tubes, nor understand the causal function of the tube. Even though there is
      evidence that they can integrate tube-related causal information to localize the
      object, they seem to depend mainly on non-causal inferences when searching for an
      invisibly displaced object.

PMID- 20136929
TI  - Online usage of theory of mind continues to develop in late adolescence.
AB  - The development of theory of mind use was investigated by giving a computerized
      task to 177 female participants divided into five age groups: Child I (7.3-9.7
      years); Child II (9.8-11.4); Adolescent I (11.5-13.9); Adolescent II (14.0-17.7);
      Adults (19.1-27.5). Participants viewed a set of shelves containing objects,
      which they were instructed to move by a 'director' who could see some but not all
      of the objects. Correct interpretation of critical instructions required
      participants to use the director's perspective and only move objects that the
      director could see. In a control condition, participants were asked to ignore
      objects in slots with a grey background. Accuracy improved similarly in both
      conditions between Child I and Adolescent II. However, while performance of the
      Adolescent II and Adult groups did not differ in the control condition, the
      Adolescent II group made more errors than the adults in the experimental
      condition. These results suggest that theory of mind use improves between late
      adolescence and adulthood. Thus, while theory of mind tasks are passed by age 4,
      these data indicate that the interaction between theory of mind and executive
      functions continues to develop in late adolescence.

PMID- 20136930
TI  - Testing the limits of statistical learning for word segmentation.
AB  - Past research has demonstrated that infants can rapidly extract syllable
      distribution information from an artificial language and use this knowledge to
      infer likely word boundaries in speech. However, artificial languages are
      extremely simplified with respect to natural language. In this study, we ask
      whether infants' ability to track transitional probabilities between syllables in
      an artificial language can scale up to the challenge of natural language. We do
      so by testing both 5.5- and 8-month-olds' ability to segment an artificial
      language containing four words of uniform length (all CVCV) or four words of
      varying length (two CVCV, two CVCVCV). The transitional probability cues to word
      boundaries were held equal across the two languages. Both age groups segmented
      the language containing words of uniform length, demonstrating that even 5.5
      month-olds are extremely sensitive to the conditional probabilities in their
      environment. However, neither age group succeeded in segmenting the language
      containing words of varying length, despite the fact that the transitional
      probability cues defining word boundaries were equally strong in the two
      languages. We conclude that infants' statistical learning abilities may not be as
      robust as earlier studies have suggested.

PMID- 20136931
TI  - Biological components of colour preference in infancy.
AB  - Adult colour preference has been summarized quantitatively in terms of weights on
      the two fundamental neural processes that underlie early colour encoding: the S
      (L+M) ('blue-yellow') and L-M ('red-green') cone-opponent contrast channels
      (Ling, Hurlbert & Robinson, 2006; Hurlbert & Ling, 2007). Here, we investigate
      whether colour preference in 4-5-month-olds may be analysed in the same way. We
      recorded infants' eye-movements in response to pairwise presentations of eight
      colour stimuli varying only in hue. Infants looked longest at reddish and
      shortest at greenish hues. Analyses revealed that the L-M and S-(L+M) contrast
      between stimulus colour and background explained around half of the variation in
      infant preference across the hue spectrum. Unlike adult colour preference
      patterns, there was no evidence for sex differences in the weights on either of
      the cone-opponent contrast components. The findings provide a quantitative model
      of infant colour preference that summarizes variation in infant preference across
      hues.

PMID- 20136932
TI  - Age differences in the contribution of recollection and familiarity to false
      memory formation: a new paradigm to examine developmental reversals.
AB  - Using a new method for studying the development of false-memory formation, we
      examined developmental differences in the rates at which 6-, 7-, 9-, 10-, and 18
      year-olds made two types of memory errors: backward causal-inference errors (i.e.
      falsely remembering having viewed the non-viewed cause of a previously viewed
      effect), and gap-filling errors (i.e. falsely remembering having viewed a script
      consistent event that was not actually witnessed). Previous research suggests
      that backward causal-inference errors are supported by recollection, whereas gap
      filling errors are supported by familiarity. We hypothesized that age differences
      in these errors would parallel the developmental trajectories of these processes.
      As predicted, age-related increases in backward causal-inference errors were
      observed, while gap-filling errors were age-invariant, suggesting that
      recollection-based memory distortions increase with age while familiarity-based
      memory distortions are relatively stable from middle childhood through adulthood.

PMID- 20136933
TI  - Two-year-olds are vigilant of others' non-verbal cues to credibility.
AB  - Data from three experiments provide the first evidence that children, at least as
      young as age two, are vigilant of others' non-verbal cues to credibility, and
      flexibly use these cues to facilitate learning. Experiment 1 revealed that 2- and
      3-year-olds prefer to learn about objects from someone who appears, through non
      verbal cues, to be confident in performing actions on those objects than from
      someone who appears uncertain when performing actions on those objects.
      Experiment 2 revealed that when 2-year-olds observe only one model perform a
      single action, either confidently or unconfidently, they do not use the model's
      level of confidence in this single instance to influence their learning.
      Experiment 3 revealed that 2-year-olds will use a single model's level of
      confidence to guide their learning if they have observed that the model has a
      history of being either consistently confident or consistently uncertain. These
      findings reveal that young children selectively alter their learning based on
      others' non-verbal cues of credibility, and underscore the importance of an early
      sensitivity to socio-cognitive cues for human learning and development.

PMID- 20136934
TI  - The emergence of a novel representation from action: evidence from preschoolers.
AB  - Recent work in embodied cognition has proposed that representations and actions
      are inextricably linked. The current study examines a developmental account of
      this relationship. Specifically, we propose that children's actions are
      foundational for novel representations. Thirty-two preschoolers, aged 3.4 to 5.7
      years, were asked to solve a set of simple gear-system problems. Participants'
      motions and verbalizations were coded to establish the strategies they used. The
      preschoolers initially solved the problems by simulating the turning and pushing
      of the gears. Subsequently, most participants discovered a new representation of
      the problems: the turning direction of the gears alternates. Results show that
      the number of actions that embodied alternation information, during their
      simulation of the system, predicted the later emergence of the higher-order
      representation (i.e. that the gears alternate turning direction). Thus, it
      appears that the preschoolers discovered a new representation based on their own
      actions. These results are consistent with the developmental embodiment
      hypothesis: actions are central to the emergence of new representations.

PMID- 20136935
TI  - Something old, something new: a developmental transition from familiarity to
      novelty preferences with hidden objects.
AB  - Novelty seeking is viewed as adaptive, and novelty preferences in infancy predict
      cognitive performance into adulthood. Yet 7-month-olds prefer familiar stimuli to
      novel ones when searching for hidden objects, in contrast to their strong novelty
      preferences with visible objects (Shinskey & Munakata, 2005). According to a
      graded representations perspective on object knowledge, infants gradually develop
      stronger object representations through experience, such that representations of
      familiar objects can be better maintained, supporting greater search than with
      novel objects. Object representations should strengthen with further development
      to allow older infants to shift from familiarity to novelty preferences with
      hidden objects. The current study tested this prediction by presenting 24 11
      month-olds with novel and familiar objects that were sometimes visible and
      sometimes hidden. Unlike 7-month-olds, 11-month-olds showed novelty preferences
      with both visible and hidden objects. This developmental shift from familiarity
      to novelty preference with hidden objects parallels one that infants show months
      earlier with perceptible stimuli, but the two transitions may reflect different
      underlying mechanisms. The current findings suggest both change and continuity in
      the adaptive development of object representations and associated cognitive
      processes.

PMID- 20136937
TI  - Abstracts of the 44th Annual Scientific Meeting of the European Society for
      Clinical Investigation. Bari, Italy. February 24-27, 2010.

PMID- 20136936
TI  - The neural basis of speech parsing in children and adults.
AB  - Word segmentation, detecting word boundaries in continuous speech, is a
      fundamental aspect of language learning that can occur solely by the computation
      of statistical and speech cues. Fifty-four children underwent functional magnetic
      resonance imaging (fMRI) while listening to three streams of concatenated
      syllables that contained either high statistical regularities, high statistical
      regularities and speech cues, or no easily detectable cues. Significant signal
      increases over time in temporal cortices suggest that children utilized the cues
      to implicitly segment the speech streams. This was confirmed by the findings of a
      second fMRI run, in which children displayed reliably greater activity in the
      left inferior frontal gyrus when listening to 'words' that had occurred more
      frequently in the streams of speech they had just heard. Finally, comparisons
      between activity observed in these children and that in previously studied adults
      indicate significant developmental changes in the neural substrate of speech
      parsing.

PMID- 20136939
TI  - Dentin/enamel bonding.

PMID- 20136940
TI  - Anterior provisional restorations used to determine form, function, and esthetics
      for complex restorative situations, using all-ceramic restorative systems.
AB  - A technique is proposed for the restoration of a large and visible maxillary
      anterior defect. The importance of proper diagnosis, treatment planning, and
      communication is emphasized. Irreversible treatment should only be rendered once
      patient approval has been obtained through objective evaluation with provisional
      restorations. The techniques presented in this article use a combination of
      ceramic systems currently available to satisfy functional demands while achieving
      acceptable esthetics. A controlled series of steps, where the provisional
      restorative components are being replaced by the definitive ones is planned. The
      only difference between the provisional and definitive restorative components is
      the material used. The definitive restorations consisted of an implant-supported
      zirconium oxide framework. Individual pressed porcelain restorations were luted
      to the framework and a natural tooth. CLINICAL SIGNIFICANCE Provisional
      restorations allow an objective form of communication. Vertical and horizontal
      transitional lines can be effectively masked with appropriate treatment planning
      and a skilled ceramist. Many traditional dental laboratory steps may be
      eliminated or simplified without compromising the definitive restorations.

PMID- 20136941
TI  - Commentary. Anterior provisional restorations used to determine form, function,
      and esthetics for complex restorative situations, using all-ceramic restorative
      systems.

PMID- 20136942
TI  - Esthetic considerations in interdental papilla: remediation and regeneration.
AB  - This article reviews the etiology and treatment of open gingival embrasures or
      black triangles. An open gingival embrasure or black triangle occurs as a result
      of a deficiency of papilla beneath the contact point. The treatment of open
      embrasures may require restorative, orthodontic and periodontal considerations
      depending on the underlying etiology. The authors reviewed a total of 42 articles
      including review of literature, radiographic, cross-sectional, and retrospective
      studies in Ovid search engine using the terms "open gingival
      embrasure,""interdental papilla," and "black triangle." The studies provided
      information regarding etiology, diagnosis, and treatment of open embrasures.
      There are several risk factors leading to the development of open gingival
      embrasures. These factors include aging, periodontal disease, loss of height of
      the alveolar bone relative to the interproximal contact, length of embrasure
      area, root angulations, interproximal contact position, and triangular-shaped
      crowns. Treatment of open embrasures requires an interdisciplinary approach of
      orthodontic, periodontic, and restorative treatment. CLINICAL SIGNIFICANCE Open
      gingival embrasures are complex esthetic and functional problems. An
      interdisciplinary team approach with the general dentist, orthodontist, and
      periodontist is critical. Management of open embrasures requires careful
      evaluation of the underlying etiology.

PMID- 20136943
TI  - Commentary. Esthetic considerations in interdental papilla: remediation and
      regeneration.

PMID- 20136944
TI  - Correlation between laser fluorescence readings and volume of tooth preparation
      in incipient occlusal caries in vitro.
AB  - OBJECTIVE: This study evaluated the correlation between laser fluorescence
      readings and the extent of incipient occlusal caries as measured by the volume of
      tooth preparation in vitro. MATERIALS AND METHODS: One hundred and three
      permanent molars and premolars containing incipient occlusal pit-and-fissure
      caries and sound occlusal surfaces (1/4 of the sample, control) were selected.
      DIAGNOdent (KaVo Dental Corporation, Lake Zurich, IL, USA) readings were obtained
      according to manufacturer instructions. Caries was removed with 1/4 round burs in
      high speed. The volume of tooth preparation was measured using a surrogate
      measure based on the amount of composite needed to fill the preparations.
      Sensitivity and specificity using different cutoff values were calculated for
      lesions/preparations extending into dentin. The results were analyzed
      statistically. RESULTS: The Pearson correlation for preparation volume and
      DIAGNOdent reading measurements was low (r = 0.285). Sensitivity and specificity
      of DIAGNOdent for detection of dentinal lesions were 0.83 and 0.60, and 0.66 and
      0.73 for the cutoff values of 20 and 30, respectively. CONCLUSIONS: Within the
      limitations of this study, laser fluorescence measured with DIAGNOdent does not
      correlate well with extent of carious tooth structure in incipient occlusal
      caries. CLINICAL SIGNIFICANCE: Clinicians should not rely only on DIAGNOdent
      readings to determine the extension of incipient occlusal caries.

PMID- 20136945
TI  - Commentary. Correlation between laser fluorescence readings and volume of tooth
      preparation in incipient occlusal caries in vitro.

PMID- 20136946
TI  - Spectrophotometric analysis of tooth color reproduction on anterior all-ceramic
      crowns: Part 1: analysis and interpretation of tooth color.
AB  - Color matching of a natural maxillary central incisor is one of the most
      difficult challenges in clinical dentistry. Accurate color determination and
      interpretation of tooth color information in ceramic work is an important step in
      achieving success in ideal color reproduction. In this case study, factors that
      influence tooth color determination were analyzed, and the process of
      interpretation of tooth color information was assessed based on scientific color
      data using a novel dental spectrophotometer system. An all-ceramic crown for a
      maxillary right central incisor was the subject of this color assessment. The
      contralateral incisor was an intact natural tooth that was bleached and then used
      as the target shade for an all-ceramic crown. The dental spectrophotometer
      (Crystaleye, Olympus, Tokyo, Japan) was used for tooth color measurement and
      analysis. The target tooth, prepared tooth, maxillary arch, and face images were
      captured for color information. Tooth color stabilization related to tooth
      bleaching and tooth dehydration was assessed. Based on tooth color data obtained
      by the dental spectrophotometer, color was analyzed in several different areas of
      a tooth using CIELAB (Commission Internationale de l'Eclarirage) color
      coordinates L*, a*, b*, and color difference Delta E. Interpretation of the tooth
      color information was made in each of porcelain layers on a blue map, and its
      intensions for color reproduction were described. Throughout this
      spectrophotometric assessment, the process of stabilized tooth color
      determination, tooth color analysis, interpretations, and fabrication of a blue
      map for porcelain work was clarified with color data as scientific evidence.
      CLINICAL SIGNIFICANCE: The use of a dedicated dental spectrophotometer allows the
      evaluation and measurement of the color of a bleached tooth. This allows the
      laboratory technician to more precisely understand the bleached tooth shade as
      well as when the bleached tooth color has become stable enough to match to a
      contralateral all-ceramic crown restoration.

PMID- 20136947
TI  - Spectrophotometric analysis of tooth color reproduction on anterior all-ceramic
      crowns: Part 2: color reproduction and its transfer from in vitro to in vivo.
AB  - Color reproduction of an anterior tooth requires advanced laboratory techniques,
      talent, and artistic skills. Color matching in a laboratory requires the
      successful transfer from in vivo with careful considerations. The purpose of this
      study was to monitor and verify the color reproduction process for an anterior
      all-ceramic crown in a laboratory through spectrophotometric measurements.
      Furthermore, a crown insertion process using composite luting cements was
      assessed, and the final color match was measured and confirmed. An all-ceramic
      crown with a zirconia ceramic coping for the maxillary right central incisor was
      fabricated. There was a significant color difference between the prepared tooth
      and the die material. The die material selected was the closest match available.
      The ceramic coping filled with die material indicated a large color difference
      from the target tooth in both lightness and chromaticity. During the first bake,
      three different approaches were intentionally used corresponding with three
      different tooth regions (cervical, body, and incisal). The first bake created the
      fundamental color of the crown that allowed some color shifts in the enamel
      layer, which was added later. The color of the completed crown demonstrated an
      excellent color match, with Delta E 1.27 in the incisal and 1.71 in the body. In
      the cervical area, color match with Delta E 2.37 was fabricated with the
      expectation of a color effect from the underlying prepared tooth. The optimal use
      of composite luting cement adjusted the effect from the underlying prepared tooth
      color, and the color match fabricated at a laboratory was successfully
      transferred to the clinical setting. The precise color measurement system leads
      to an accurate verification of color reproduction and its transfer. CLINICAL
      SIGNIFICANCE The use of a dedicated dental spectrophotometer during the
      fabrication of an all-ceramic crown allows the dentist and the laboratory
      technician to accurately communicate important information to one another about
      the shade of the tooth preparation, the shade of the contralateral target tooth,
      and the influence of luting cement on the final restoration, thereby allowing the
      technician better control over the outcome of their tooth color matching efforts
      and the final color match of an all-ceramic restoration.

PMID- 20136948
TI  - Commentary. Spectrophotometric analysis of tooth color reproduction on anterior
      all-ceramic crowns: Part 1: analysis and interpretation of tooth color, Part 2:
      color reproduction and its transfer from in vitro to in vivo.

PMID- 20136949
TI  - Keys to success in creating esthetic class IV restorations.

PMID- 20136950
TI  - Critical appraisal. Options for dentin/enamel bonding: Part I.
AB  - Four categories of resin-based dentin/enamel adhesives are currently available.
      These include the three-step etch-and-rinse, "one-bottle" etch-and-rinse, two
      step self-etch primer systems, and "all-in-one" self-etch adhesives. In
      consecutive issues of the Journal, the Critical Appraisal series will present
      salient publications on research in each of the categories, beginning with this
      issue's piece on the three-step etch-and-rinse systems.

PMID- 20136953
TI  - Taking optical biopsies with confocal endomicroscopy.

PMID- 20136954
TI  - Red wine coming up roses for intestinal ischemia reperfusion injury: role for
      resveratrol?

PMID- 20136955
TI  - Non-alcoholic fatty liver disease: confronting the global epidemic requires
      better awareness.

PMID- 20136956
TI  - Targeting circulatory dysfunction in cirrhosis: terlipressin and the hepatorenal
      syndrome.

PMID- 20136957
TI  - Can wire-guided cannulation reduce the risk of post-endoscopic retrograde
      cholangiopancreatography pancreatitis? A meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND AND AIM: The use of wire-guided cannulation (WGC) for prevention of
      post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is
      controversial. The aim of the present study was to assess the overall effect of
      WGC for PEP compared with conventional contrast-assisted cannulation by carrying
      out a meta-analysis of all available randomized controlled trials (RCT). METHODS:
      Electronic databases, including PubMed, EMBASE, the Cochrane library and the
      Science Citation Index, were searched to retrieve relevant trials. In addition,
      meeting abstracts and the reference lists of retrieved articles were reviewed for
      further relevant studies. Outcome measures were the incidence of PEP. RESULTS:
      Four RCT, enrolling a total of 1413 patients, were included. The meta-analysis
      failed to indicate a significant association between the use of WGC and the
      reduction of PEP (RR 0.34; 95% CI: 0.10-1.17; P = 0.09). Subgroup analysis
      including trials without cross-over design showed a significant benefit with the
      use of WGC in reducing PEP (RR 0.20; 95% CI: 0.09-0.40; P < 0.00001) and trials
      without precut used failed to indicate a significant differences between the two
      group (RR 0.38; 95% CI: 0.01-11.73; P = 0.58). CONCLUSIONS: This meta-analysis
      showed only a non-significant reduction in the rate of PEP with the use of WGC.
      Further well-designed RCT are required to confirm the effect of WGC, especially
      in patients who were easier to cannulate.

PMID- 20136958
TI  - Major adverse events, pretransplant assessment and outcome prediction.
AB  - Liver cirrhosis and portal hypertension pose enormous loss of lives and resources
      throughout the world, especially in endemic areas of chronic viral hepatitis.
      Although the pathophysiology of cirrhosis is not completely understood, the
      accumulating evidence has paved the way for better control of the complications,
      including gastroesophageal variceal bleeding, hepatic encephalopathy, ascites,
      hepatorenal syndrome, hepatopulmonary syndrome and portopulmonary hypertension.
      Modern pharmacological and interventional therapies have been designed to treat
      these complications. However, liver transplantation (LT) is the only definite
      treatment for patients with preterminal end-stage liver disease. To pursue
      successful LT, the meticulous evaluation of potential recipients and donors is
      pivotal, especially for living donor transplantation. The critical shortage of
      cadaveric donor livers is another concern. In many Asian countries, cultural and
      religious concerns further limit the number of the donors, which lags far behind
      that of the recipients. The model for end-stage liver disease (MELD) scoring
      system has recently become the prevailing criterion for organ allocation. Initial
      results showed clear benefits of moving from the Child-Turcotte-Pugh-based system
      toward the MELD-based organ allocation system. In addition to the MELD, serum
      sodium is another important prognostic predictor in patients with advanced
      cirrhosis. The incorporation of serum sodium into the MELD could enhance the
      performance of the MELD and could become an indispensable strategy in refining
      the priority for LT. However, the feasibility of the MELD in combination with
      sodium in predicting the outcome for patients on transplant waiting list awaits
      actual outcome data before this becomes standard practice in the Asia-Pacific
      region.

PMID- 20136960
TI  - Fecal lactoferrin, myeloperoxidase and serum C-reactive are effective biomarkers
      in the assessment of disease activity and severity in patients with idiopathic
      ulcerative colitis.
AB  - BACKGROUND AND AIM: Disease activity and severity of ulcerative colitis (UC) is
      assessed using colonoscopy, which is invasive, costly and has poor patient
      acceptability. The role of non-invasive biomarkers of intestinal inflammation in
      the evaluation of patients with UC is not known. The aim of the study was to
      examine the role of serum C-reactive protein (SCRP), fecal myeloperoxidase (FMPO)
      and fecal lactoferrin (FLF) in assessing disease severity, activity and response
      to therapy. METHODS: Consecutive patients with idiopathic UC (IUC) attending our
      hospital from July 2005 to September 2006 were studied. All underwent clinical,
      endoscopic and histological assessment for disease activity, extent, severity and
      estimation of SCRP, FMPO and FLF levels at baseline and follow up (FU). An equal
      number of healthy age-matched controls were studied for biomarker levels.
      RESULTS: A total of 37 patients (mean age 37 +/- 12 years) were studied. All
      three biomarkers were elevated more often in the cases than in the controls (all
      P = 0.000). Cases with severe IUC had higher CRP, MPO and FLF titers than those
      without severe IUC. At FU, a significant fall in biomarker levels paralleled the
      reduction in Mayo's scores. All three biomarkers showed a high degree of
      correlation with each other. The areas under the curve for FLF, MPO and CRP were
      1.00, 0.867 and 0.622, respectively. The sensitivity and specificity of markers
      were: FLF (94%, 100%), FMPO (89%, 51%) and SCRP (24%, 100%). CONCLUSION:
      Biomarkers are useful in assessing disease activity, severity and response to
      therapy in patients with UC. They showed a high degree of correlation with each
      other.

PMID- 20136959
TI  - Influence of inflammatory cytokine polymorphisms on eradication rates of
      Helicobacter pylori.
AB  - Pro-inflammatory cytokines and anti-inflammatory cytokines are produced in
      gastric mucosa from inflammatory cells activated by Helicobacter pylori (H.
      pylori) infection. Of the inflammatory cytokines, interleukin (IL)-1beta and
      tumor necrosis factor (TNF)-alpha have a potent inhibitive effect on gastric acid
      production. Polymorphisms in these genes are associated with individual
      differences in cytokine messenger RNA levels, which result in different gastric
      mucosal inflammation, different acid inhibition and different gastroduodenal
      disease risks in response to H. pylori infection. The sustained higher
      intragastric pH during an eradication therapy is known to be one of the
      therapeutic determinants of the H. pylori eradication as well as antibiotics
      resistance and poor compliance. The IL-1B-511 polymorphism is related to
      eradication rate, and, in combined analysis of previous reports, the eradication
      rate in patients with the IL-1B-511 C/C genotype (77.4%, 209/270), low IL-1beta
      producer genotype, is lower than that of the IL-1B-511 C/T and T/T genotypes
      (87.2%, 631/724) (Odds ratio for eradication failure: 1.98, 95% confidence
      interval: 1.38-2.84, P = 0.0002). Moreover, the odds ratio of combined CYP2C19
      rapid metabolizer-IL-1B-511 C/C type for eradication failure is 11.15 (5.23
      23.78) times that of the CYP2C19 poor metabolizer-IL-1B-511 non-C/C type.
      However, there is no positive data indicating the role of other inflammatory
      cytokine polymorphisms (e.g. IL-1RN, TNF-A or IL-10) in eradication therapy.
      Nevertheless, the studies show that inflammatory cytokine polymorphisms,
      especially the IL-1B-511 T/T genotype, are the determinants of eradication by
      affecting gastric acid secretion and mucosal inflammation. Therefore, the
      tailored eradication therapy, considering inflammatory cytokine polymorphisms,
      may be effective for the higher eradication rates.

PMID- 20136961
TI  - Preventive effects of Schistosoma japonicum ova on trinitrobenzenesulfonic acid
      induced colitis and bacterial translocation in mice.
AB  - AIMS: To evaluate the preventive effects of Schistosoma japonicum ova on
      trinitrobenzenesulfonic acid (TNBS)-induced colitis and bacterial translocation
      in mice. METHODS: BALB/c mice were randomly divided into three groups: control
      group; TNBS(+)Ova(-) group; and TNBS(+)Ova(+) group. Mice of the TNBS(+)Ova(+)
      group were exposed to 10 000 freeze-killed S. japonicum ova by i.p. injection on
      day 1 and day 11. On day 15, mice were challenged with TNBS to induce colitis.
      The following variables were assessed: colon pathological changes; serum
      expression of tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (IFN
      gamma) and interleukin-10 (IL-10); expression of Toll-like receptor 4 (TLR4) in
      colon; IFN-gamma, IL-10 and TLR4 mRNA expression in colon; and the bacterial
      translocation rate. RESULTS: Compared to TNBS(+)Ova(-) group, the colonic
      inflammation in the TNBS(+)Ova(+) group were relieved. A highly significant
      elevation of IFN-gamma and TNF-alpha were observed in the TNBS-induced colitis
      group. After exposure to the eggs, IFN-gamma was significantly decreased, while
      TNF-alpha was similar to that of the TNBS(+)ova(-) group. No obvious variation
      was seen in IL-10 expression in TNBS-induced colitis, compared to the controls.
      Exposure to the eggs led to a significant upregulation of IL-10 expression. TLR4
      expression was elevated after injected with TNBS and was downregulated in the
      eggs group. Less intestinal bacterial translocation frequency was observed when
      exposed to eggs. CONCLUSION: S. japonicum ova can prevent the TNBS-induced
      colitis and reduce the bacterial translocation frequency in mice. The mechanisms
      were supposed to be due to the regulation of T-helper cell 1/2 balance and TLR4
      expression.

PMID- 20136962
TI  - Education and Imaging. Gastrointestinal: positron emission tomography (PET) in
      intestinal tuberculosis: masquerading hot spots.

PMID- 20136963
TI  - Education and Imaging. Colonic perforation during 'virtual' CT colonography.

PMID- 20136964
TI  - Education and Imaging. Hepatobiliary and pancreatic: nodular regenerative
      hyperplasia of the liver.

PMID- 20136967
TI  - Coagulopathy in liver disease: the whole is greater than the sum of its parts.

PMID- 20136968
TI  - PAHA model: an alternative non-invasive predictor of liver cirrhosis in patients
      with chronic hepatitis B infection.

PMID- 20136969
TI  - Cow's milk protein allergy: an entity for recognition in developing countries.

PMID- 20136970
TI  - Immediate-release oral proton pump inhibitors: Panacea or a flash in the pan?

PMID- 20136971
TI  - Second-look endoscopy with thermal coagulation or injections for peptic ulcer
      bleeding: a meta-analysis.
AB  - BACKGROUND AND AIMS: In the management of peptic ulcer bleeding, the benefits of
      second-look endoscopic treatment with thermal coagulation or injections in
      controlling recurrent bleeding is unsure. This study set out to compare efficacy
      of routine second-look endoscopy with treatment using either thermal coagulation
      or injections versus single endoscopy by pooling data from published work.
      METHODS: Full publications in the English-language published work as well as
      abstracts in major international conferences were searched over the past 10
      years, and six trials fulfilling the search criteria were found. Outcome
      measurements included: (i) recurrent bleeding; (ii) requirement of surgical
      intervention; and (iii) mortality. We examined heterogeneity of trials and pooled
      the effects by meta-analysis. The quality of studies was graded according to the
      prospective randomization, methods of patient allocation, the list of exclusion
      criteria, outcome definitions and the predefined salvage procedures for
      uncontrolled bleeding. RESULTS: Among 998 patients recruited in these five
      randomized trials, 119 received routine second-look endoscopy with thermal
      coagulation, and 374 received second-look with endoscopic injection and 505 had
      single endoscopic therapy. Less recurrent bleeding was reported after thermal
      coagulation (4.2%) than single endoscopy (15.7%) (relative risk [RR] = 0.29; 95%
      confidence interval [CI] = 0.11-0.73), but no reduction was reported for the
      requirement of surgical intervention and all-cause mortality. Injection therapy
      did not reduce re-bleeding (17.6%) when compared to single endoscopy (20.8%; RR =
      0.85; 95% CI = 0.63-1.14), requirement for surgery and mortality. CONCLUSION:
      Routine second-look endoscopy with thermal coagulation, but not injection
      therapy, reduced recurrent peptic ulcer bleeding. There is no proven benefit in
      reducing surgical intervention and overall mortality.

PMID- 20136972
TI  - Toward elimination and eradication of hepatitis B.
AB  - Hepatitis B virus (HBV) causes important human health problems. It has infected
      one-third of the world's population and approximately 360 million people are
      chronic carriers. Worldwide, 0.5-1.2 million deaths are attributed to HBV
      infection annually. Therefore, global control of HBV infection is important. HBV
      infection can be intervened by interrupting routes of transmission, treating the
      chronically infected, and preventing the susceptibles with immunoprophylaxis. All
      these measures are effective. Nevertheless, although pegylated interferons or
      nucleos(t)ide analogs are effective for the treatment of chronic hepatitis B,
      chronic carriage of HBV is not easy to eliminate, as revealed by the frequent
      persistence of hepatitis B surface antigen, despite satisfactory responses to
      these treatments. On the other hand, hepatitis B vaccination has been shown to
      preclude HBV infection effectively. This is particularly true for pre-exposure
      prophylaxis. Worthy of note is the universal vaccination of newborn infants. This
      is the most effective means of preventing HBV infection, especially for those
      born to HBV carrier mothers. To eliminate and eradicate hepatitis B, first, HBV
      in the chronically infected should be eradicated or strongly and efficiently
      suppressed, so that the infection does not spread rampantly. Second, all the
      transmission routes should be interrupted. Lastly, but most effectively, is to
      immunize all susceptibles. The difficulties and possible solutions of each
      approach are discussed. In conclusion, the existing means to prevent and treat
      HBV infection render our goal toward eliminating and eradicating hepatitis B
      possible, although it will take much time and effort to achieve this objective.

PMID- 20136973
TI  - Helicobacter pylori colonization of the human gastric epithelium: a bug's first
      step is a novel target for us.
AB  - After Helicobacter pylori enters the stomach, three steps are vital for
      infection: (i) establishing colonization; (ii) evading host immunity; and (iii)
      invading gastric mucosa; the last step is what is associated with diverse
      outcomes. Urease activity and motility mediated by the flagella of H. pylori are
      important in harboring colonies beneath the gastric mucus in niches adjacent to
      the epithelium. Several putative adhesins attach the organism to the gastric
      epithelium and prompt the succeeding processes for evading host immunity and
      invading the mucosa. Successful colonization is thus the leading and critical
      step. From another point of view, this can be a novel target to control this
      common and important infection. This review summarizes the putative adhesins that
      influence the evasion of host immunity, and how these could determine different
      clinico-pathologic outcomes. The putative adhesins include the interplay between
      bacterial and host Lewis antigens (type I: Le(a) and Le(b); type II: Le(x) and
      Le(y)), the dominant pathway between BabA and Le(b), the SabA adhesin binding to
      sialylated Le(x) that is upregulated in inflamed gastric tissue or those with
      weak-Le(b), the CagL apparatus to adapt with the alpha5beta1 integrin to mediate
      a type IV secretory system for CagA translocation into the epithelium; and other
      outer membrane proteins as HopZ, AlpA/AlpB, or OipA, without known corresponding
      receptors. This review implicates the adhesins vital for bugs that could be
      alternatively provided as novel targets for us to overcome the colonization.

PMID- 20136974
TI  - Anti-inflammatory actions of probiotics through activating suppressor of cytokine
      signaling (SOCS) expression and signaling in Helicobacter pylori infection: a
      novel mechanism.
AB  - BACKGROUND AND AIMS: In spite of the International Agency for Research on
      Cancer's definition that Helicobacter pylori is the definite carcinogen of
      gastric cancer, the simple eradication of the bug is not enough to prevent
      resultant gastric cancer, and increasing microbial resistance further limits the
      eradication application. Therefore, probiotics, non-pathogenic microbial feed
      that can affect the host in a beneficial manner, could be an alternate way to
      enhance anti-inflammation against H. pylori. However, the mechanism of their anti
      inflammatory actions is still unclear. In the current study, we hypothesized that
      suppressor of cytokine signaling (SOCS) signaling could be a feasible anti
      inflammatory mechanism of probiotics against H. pylori infection. RESULTS: H.
      pylori infection or their lipopolysaccharide stimulation led to significant
      increased expressions of inflammatory mediators including tumor necrosis factor
      alpha, interleukin-8, inducible nitric oxide synthase and cyclooxygenase-2 in AGS
      cells and pretreatment of Lactobacillus plantarum, Lactobacillus rhamnosis and
      Lactobacillus acidophilus significantly attenuated the expressions of these
      inflammatory mediators in accordance with the blocking action of nuclear factor
      kappaB nuclear translocation. Probiotic administration increased expression of
      SOCS-2 and SOCS-3 and exerted the active SOCS signaling featured with earlier and
      higher expressions of SOCS-2 and SOCS-3. In contrast to weak inactivation of
      mitogen-activated protein kinases including p-38 and extracellular signal
      regulated kinase 1/2, probiotic-induced SOCS expressions were mediated through
      either significant phosphorylation of signal transducers and activation of
      transcription (STAT)-1 and STAT-3 or simultaneous inhibition of Janus kinase
      (JAK)2 phosphorylation, which is known to signal SOCS-2/SOCS-3 negatively.
      CONCLUSION: Anti-inflammatory signals of SOCS through STAT-1/STAT-3 activation
      and JAK2 inactivation might be a key anti-inflammatory mechanism of probiotics,
      setting probiotics as a non-microbial strategy to H. pylori infection.

PMID- 20136975
TI  - Education and imaging. Gastrointestinal: Improvement of granuloma annulare with
      anti-tumour necrosis factor alpha therapy for Crohn's disease.

PMID- 20136976
TI  - Education and imaging. Gastrointestinal: an uncommon intra-abdominal foreign
      body.

PMID- 20136977
TI  - Education and imaging. Gastrointestinal: Spontaneous pancreaticoduodenal fistula
      associated with acute necrotizing pancreatitis.

PMID- 20136978
TI  - Education and imaging. Hepatobiliary and pancreatic: Budd-Chiari syndrome
      secondary to leiomyosarcoma of the inferior vena cava.

PMID- 20136979
TI  - Education and imaging. Hepatobiliary and pancreatic: Budd-Chiari syndrome
      presenting as a caudate lobe pseudotumor.

PMID- 20136983
TI  - Occult hepatitis B virus infection in patients with chronic hepatitis C: An actor
      behind the scene or just a bystander?

PMID- 20136984
TI  - Does non-alcoholic fatty liver disease predispose patients to type 2 diabetes in
      the absence of obesity?

PMID- 20136986
TI  - Environmental risk factors in inflammatory bowel disease.

PMID- 20136987
TI  - Marshall and Warren Lecture 2009: peptic ulcer bleeding: an expedition of 20
      years from 1989-2009.
AB  - Peptic ulcer bleeding is one of the most common medical emergencies leading to
      substantial mortality and morbidity. The last two decades has witnessed some
      important advances in the management of this condition, and some of these are
      results from clinical trials conducted in the Asia Pacific region. The optimal
      use of combined endoscopic hemostasis and the use of pharmacologic control of
      acid secretion in the stomach have significantly improved clinical outcome. The
      role of surgery has been redefined. Treatment of Helicobacter pylori infection
      and prophylactic treatment in non-steroidal anti-inflammatory drug and anti
      platelet users have made progress in preventing recurrence of peptic ulcer and
      bleeding. Instead of merely focusing on safety in the gastrointestinal tract,
      striking a balance between risk and benefit of continuing anti-platelet agents
      should be a top agenda.

PMID- 20136988
TI  - Gastrointestinal and biliary stents.
AB  - Advances in stent design have led to a substantial increase in the use of stents
      for a variety of malignant and benign strictures in the gastrointestinal tract
      and biliary system. Whereas early stents were mostly composed of plastic, the
      majority of contemporary stents are self-expanding metal stents that are composed
      of either nitinol or stainless steel. These stents are able to exert an adequate
      expansile force and, at the same time, are highly flexible and biocompatible.
      Covered stents have been introduced to minimize tumor ingrowth through the metal
      mesh but are associated with higher rates for spontaneous migration. This has led
      to the development of covered stents with uncovered ends and stents with both
      covered and uncovered layers. Drug-eluting and biodegradable stents are also
      likely to become available in the near future. Although stents appear to be the
      preferred form of palliation for some patients with advanced cancer, many
      patients will benefit from a multidisciplinary approach that usually includes
      surgeons and oncologists.

PMID- 20136989
TI  - Evidence-based dietary management of functional gastrointestinal symptoms: The
      FODMAP approach.
AB  - BACKGROUND AND AIM: Functional gastrointestinal symptoms are common and their
      management is often a difficult clinical problem. The link between food intake
      and symptom induction is recognized. This review aims to describe the evidence
      base for restricting rapidly fermentable, short-chain carbohydrates (FODMAPs) in
      controlling such symptoms. METHODS: The nature of FODMAPs, their mode of action
      in symptom induction, results of clinical trials and the implementation of the
      diet are described. RESULTS: FODMAPs are widespread in the diet and comprise a
      monosaccharide (fructose), a disaccharide (lactose), oligosaccharides (fructans
      and galactans), and polyols. Their ingestion increases delivery of readily
      fermentable substrate and water to the distal small intestine and proximal colon,
      which are likely to induce luminal distension and induction of functional gut
      symptoms. The restriction of their intake globally (as opposed to individually)
      reduces functional gut symptoms, an effect that is durable and can be reversed by
      their reintroduction into the diet (as shown by a randomized placebo-controlled
      trial). The diet has a high compliance rate. However it requires expert delivery
      by a dietitian trained in the diet. Breath hydrogen tests are useful to identify
      individuals who can completely absorb a load of fructose and lactose so that
      dietary restriction can be less stringent. CONCLUSIONS: The low FODMAP diet
      provides an effective approach to the management of patients with functional gut
      symptoms. The evidence base is now sufficiently strong to recommend its
      widespread application.

PMID- 20136990
TI  - Education and Imaging. Gastrointestinal: Pseudomelanosis duodeni.

PMID- 20136991
TI  - Education and Imaging. Gastrointestinal: oesophageal perforation during endoscopy
      for food impaction in eosinophilic oesophagitis.

PMID- 20136992
TI  - Education and Imaging. Gastrointestinal: Enterolith-induced perforation on a
      background of jejunal diverticulum.

PMID- 20136993
TI  - Education and Imaging. Hepatobiliary and pancreatic: Delayed ileal perforation
      following radiofrequency ablation of hepatocellular carcinoma.

PMID- 20136994
TI  - Education and Imaging. Hepatobiliary and pancreatic: Biliary rupture of an
      hydatid cyst.

PMID- 20136996
TI  - Poisons in pets.

PMID- 20136997
TI  - Life, the universe and everything.

PMID- 20136998
TI  - Proportion of litters of purebred dogs born by caesarean section.
AB  - OBJECTIVES: To describe the frequency of caesarean sections in a large sample of
      pedigree dogs in the UK. METHODS: Data on the numbers of litters born in the
      previous 10 years were available from a cross-sectional study of dogs belonging
      to breed club members (2004 Kennel Club/BSAVA Scientific Committee Purebred Dog
      Health Survey). In this survey 151 breeds were represented with data for
      households that had reported on at least 10 litters (range 10-14,15): this
      represented 13,141 bitches which had whelped 22,005 litters. The frequency of
      caesarean sections was estimated as the percentage of litters that were reported
      to be born by caesarean section (caesarean rates) and are reported by breed. The
      dogs were categorised into brachycephalic, mesocephalic and dolicocephalic
      breeds. RESULTS: The 10 breeds with the highest caesarean rates were the Boston
      terrier, bulldog, French bulldog, mastiff, Scottish terrier, miniature bull
      terrier, German wirehaired pointer, Clumber spaniel, Pekingese and Dandie Dinmont
      terrier. In the Boston terrier, bulldog and French bulldog, the rate was > 80%.
      CLINICAL SIGNIFICANCE: These data provide evidence for the need to monitor
      caesarean rates in certain breeds of dog.

PMID- 20136999
TI  - Late onset and rapid progression of cerebellar abiotrophy in a domestic shorthair
      cat.
AB  - A two-year-old male domestic shorthair cat was seen because of sudden onset of
      incoordination and tremors that had rapidly worsened over five days. Neurological
      examination revealed severe cerebellar ataxia, intention tremors and bilaterally
      decreased menace response. Blood work evaluation included a complete cell blood
      count (CBC), serum biochemistry profile, urinalysis, faecal flotation,
      cerebrospinal fluid (CSF) analysis and retroviral testing. Except for testing
      positive for feline immunodeficiency virus (FIV) antibodies, all other results
      were within the normal range. The patient was euthanased two days later because
      of progression of clinical signs, and a necropsy was performed. Histologically,
      lesions were limited to the cerebellum and consistent with cerebellar abiotrophy.
      No secondary diseases that could explain the rapid development of clinical signs
      were found. It was considered unlikely that cerebellar degeneration was related
      to FIV positivity, as virus invasion of the central nervous system (CNS) is
      mainly limited to the cerebral cortex. This case report is the first to describe
      late onset and rapid progression cerebellar abiotrophy in a cat.

PMID- 20137000
TI  - Toxicities and salvage therapy following overdose of vinblastine in a cat.
AB  - A cat receiving chemotherapy for lymphoma was administered a four times overdose
      of vinblastine in error. Severe, acute life-threatening toxicities occurred. The
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was suspected
      based on electrolyte disturbances. A favourable outcome was achieved with
      aggressive supportive care. Personnel involved in administering chemotherapy to
      small animal patients must check that the patient is receiving the correct drug,
      at the appropriate dose, prior to every treatment.

PMID- 20137001
TI  - Use of venlafaxine in the treatment of a canine narcolepsy-cataplexy case.

PMID- 20137002
TI  - Down on the farm.

PMID- 20137004
TI  - Emesis in dogs: a review.
AB  - Emesis is a common presenting sign in small animal practice. It requires a
      rational approach to management that is based upon a sound understanding of
      pathophysiology combined with logical decision making. This review, which
      assesses the weight of available evidence, outlines the physiology of the
      vomiting reflex, causes of emesis, the consequences of emesis and the approach to
      clinical management of the vomiting dog. The applicability of diagnostic testing
      modalities and the merit of traditional approaches to management, such as dietary
      changes, are discussed. The role and usefulness of both traditional and novel
      anti-emetic drugs is examined, including in specific circumstances such as
      following cytotoxic drug treatment. The review also examines areas in which
      common clinical practice is not necessarily supported by objective evidence and,
      as such, highlights questions worthy of further clinical research.

PMID- 20137005
TI  - Assessment of the incidence of GDV following splenectomy in dogs.
AB  - OBJECTIVE: To establish if splenectomy increases the incidence of gastric
      dilatation and volvulus (GDV) in dogs. METHODS: Two case-series studies of cases
      and controls were performed. Records of dogs that had undergone splenectomy (37
      cases) were compared with records of dogs that had undergone other abdominal
      surgery (43 cases). Records of dogs that presented for non-elective gastropexy
      (33 cases) were compared with records of dogs presented to the hospital for
      unrelated reasons (39 cases). Survival following splenectomy and development of
      GDV in the first 12 months following surgery were retrieved from the clinical
      records and by questionnaire-based canvassing of the referring clinician. The
      incidence of GDV following splenectomy was established and the association
      between a current episode of GDV and previous splenectomy was assessed. RESULTS:
      There was no evidence that splenectomy was associated with an increased incidence
      of subsequent GDV (P=0.469). No association between a current episode of GDV and
      previous splenectomy was found. CLINICAL SIGNIFICANCE: Splenectomy is not
      associated with an increase in the incidence of GDV.

PMID- 20137006
TI  - Sand impaction of the small intestine in eight dogs.
AB  - OBJECTIVE: To describe signalment, clinical findings, imaging and treatment of
      intestinal sand impaction in the dog. METHODS: Medical records of dogs with
      radiographic evidence of small intestinal sand impaction were reviewed. RESULTS:
      Sand impaction resulting in small intestinal obstruction was diagnosed in eight
      dogs. All dogs presented with signs of vomiting. Other clinical signs included
      anorexia, lethargy and abdominal pain. Radiographs confirmed the presence of
      radio-opaque material consistent with sand causing distension of the terminal
      small intestine in all dogs. Four dogs were treated surgically for their
      impaction and four dogs were managed medically. Seven of the eight dogs survived.
      CLINICAL SIGNIFICANCE: Both medical and surgical management of intestinal sand
      impaction in the dog can be effective and both afford a good prognosis for
      recovery.

PMID- 20137007
TI  - Effects of a probiotic intervention in acute canine gastroenteritis--a controlled
      clinical trial.
AB  - OBJECTIVES: To evaluate the effect of a probiotic product in acute self-limiting
      gastroenteritis in dogs. METHODS: Thirty-six dogs suffering from acute diarrhoea
      or acute diarrhoea and vomiting were included in the study. The trial was
      performed as a randomised, double blind and single centre study with stratified
      parallel group design. The animals were allocated to equal looking probiotic or
      placebo treatment by block randomisation with a fixed block size of six. The
      probiotic cocktail consisted of thermo-stabilised Lactobacillus acidophilus and
      live strains of Pediococcus acidilactici, Bacillus subtilis, Bacillus
      licheniformis and Lactobacillus farciminis. RESULTS: The time from initiation of
      treatment to the last abnormal stools was found to be significantly shorter (P =
      0.04) in the probiotic group compared to placebo group, the mean time was 1.3
      days and 2.2 days, respectively. The two groups were found nearly equal with
      regard to time from start of treatment to the last vomiting episode. CLINICAL
      SIGNIFICANCE: The probiotic tested may reduce the convalescence time in acute
      self-limiting diarrhoea in dogs.

PMID- 20137008
TI  - Recovery of dermatophytes in pet grooming tools from veterinary clinics and pet
      grooming salons.
AB  - OBJECTIVES: Fomites such as brushes and clippers are known to be potential risk
      factors for the transmission of dermatophytes between pet animals. The aim of
      this study was to investigate this risk by examining those grooming implements
      for the presence of any viable dermatophytes. METHODS: For this purpose, samples
      from 235 pieces of grooming equipment and swab samples from the surface of the 14
      grooming tables were taken from 41 veterinary clinics and 3 pet grooming salons.
      RESULTS: Trichophyton tonsurans was isolated from two clipper blades from one
      veterinary clinic and Microsporum canis were isolated from three clipper blades
      and one toothbrush from another clinic. CLINICAL SIGNIFICANCE: This study shows
      that current disinfection protocols and grooming procedures of the veterinary
      clinics and pet grooming salons appear to be adequate.

PMID- 20137009
TI  - Meningeal carcinomatosis in a dog: magnetic resonance imaging features and
      pathological correlation.
AB  - A six-year-old cross breed dog was presented with a four-month history of seizure
      activity, which was unresponsive to anticonvulsive therapy and an acute
      deterioration in neurological status, evident as central blindness. Cyst-like
      structures and nodular enhancement within the subarachnoid space were shown on a
      magnetic resonance image (MRI) scan. Histopathological examination of brain
      tissue was consistent with meningeal carcinomatosis.

PMID- 20137010
TI  - Use of a biodegradable self-expanding stent in the management of a benign
      oesophageal stricture in a cat.
AB  - An 11-year-old domestic shorthair cat presented with a six-week history of
      regurgitation following a dental procedure. Endoscopy identified a single
      oesophageal stricture in the cervical oesophagus. Stricture reformation occurred
      following endoscopic balloon catheter dilation on two occasions. Following a
      third balloon dilation a biodegradable polydioxanone self-expanding stent was
      placed across the stricture site. Following the implantation the cat was able to
      eat soft canned food orally without regurgitation. Fluoroscopic examination
      performed four months after placement indicated that the stent was no longer
      present and the cervical oesophagus was able to pass boluses of canned food with
      no signs of obstruction.

PMID- 20137013
TI  - Effect of storage time on dog urine.

PMID- 20137020
TI  - Retention priorities for the intergenerational nurse workforce.
AB  - TOPIC: Retention of senior, Gen-X, and Millennial nurses is influenced by manager
      interactions and efforts to create a satisfying work experience. PURPOSE: The
      purpose of this project was a generational assessment of job satisfaction, work
      environment, and desired characteristics of managers in an effort to improve
      nurse retention. SAMPLE AND METHODS: Data from staff nurses at 22 southern
      hospitals collected by online survey included measures of job satisfaction and
      perceptions of safety, the Nurse Manager Desired Traits survey, and the Nursing
      Work Index-Revised. FINDINGS: The satisfaction with work environment scores for
      the whole group (n = 1,773) were high. Subscale scores showed highest
      satisfaction with nurse/physician relationships; lowest was nurse control of
      practice. A specific satisfaction question showed the younger nurses were less
      satisfied than those over age 40. Nurse safety concerns were expressed by 40% of
      the sample. One third of Millennial nurses plan to leave their job within the
      next 2 years. Over two thirds plan to be gone within the next 5 years. Especially
      alarming is the fact that 61% of the nurse group stated they plan to leave their
      current jobs within 10 years. RECOMMENDATIONS: (a) Create model managers; (b)
      empower staff nurse councils; (c) stabilize staffing; (d) revamp incentives; and
      (e) focus on safety.

PMID- 20137021
TI  - "Leaving the comfort of the familiar": fostering workplace cultural awareness
      through short-term global experiences.
AB  - PROBLEM: Facilitating the development of student nurses' cultural competence and
      translating these experiences into the clinical setting. METHODS: Qualitative
      methods. FINDINGS: A short-term global immersion experience informs student
      nurses' cultural awareness, education, and future clinical practice. CONCLUSIONS:
      Participation in a short-term global health experience contributes to students'
      personal growth and broadens their insight into multicultural care.

PMID- 20137022
TI  - Immunizing children who fear and resist needles: is it a problem for nurses?
AB  - BACKGROUND: Despite increasing evidence that immunization procedures can be
      stressful for children, little is known about what the experience of immunizing
      frightened and needle-resistant children can be like for nurses. METHOD: This
      article presents findings from a qualitative research project designed to explore
      public health nurses' feelings toward immunizing needle-resistant children. A
      constructivist theoretical perspective and an action research approach framed the
      study. Data sources included two survey questions and audio-recorded transcribed
      data from three focus groups. Participants included 35 public health nurses from
      five different health units in one Canadian province. The data were analyzed for
      themes and were confirmed with participants through ongoing member checking.
      RESULTS: The following four overarching themes were identified and are used to
      explain and describe significant features of the immunization experience that
      were stressful and problematic for nurses: (a) nurses experience stress when
      immunizing children who fear and resist needle injection; (b) the strength of
      child resistance and some adult behavior creates an ethical dilemma for nurses;
      (c) some adult responses make immunizing difficult and unsafe; and (d) resources
      to help nurses cope with these situations are inconsistent.

PMID- 20137023
TI  - Economic theory and nursing administration research--is this a good combination?
AB  - TOPIC: Economic theory is used to describe and explain decision making in the
      context of scarce resources. PURPOSE: This paper presents two applications of
      economic theory to the delivery of nursing services in acute care hospitals and
      evaluates its usefulness in guiding nursing administration research. SOURCES OF
      INFORMATION: The description of economic theory and the proposed applications for
      nursing are based on current nursing, healthcare, and economic literature.
      Evaluation of the potential usefulness of economic theory in guiding nursing
      administration research is based on the criteria of significance and testability
      as described by Fawcett and Downs. CONCLUSIONS: While economic theory can be very
      useful in explaining how decisions about nursing time allocation and nursing care
      production are made, it will not address the issue of how they should be made.
      Normative theories and ethical frameworks also must be incorporated in the
      decision-making process around these issues. Economic theory and nursing
      administration are a good fit when balanced with the values and goals of nursing.

PMID- 20137024
TI  - Intimidation: a concept analysis.
AB  - PROBLEM: Patient safety is being compromised by intimidating communication and
      ineffective teamwork among healthcare providers. The Joint Commission Update
      indicates that ineffective communication has been the leading root cause of the
      majority of sentinel events since 1996. Furthermore, the organizational
      implementation of policies and procedures for addressing this dangerous situation
      is now mandated by The Joint Commission Sentinel Event Alert. However, in order
      to consistently identify and address this problem, there must be a clear and
      universal definition of intimidation. METHODS: The purpose of this article is to
      clarify the definition of intimidation in healthcare settings. Without this
      clarity, the role of intimidation as a precursor to the occurrence of medical
      errors will inevitably be obscured. The framework for concept analysis proposed
      by Walker and Avant is used to explicate the definition, attributes, antecedents,
      consequences, and cases of intimidation. FINDINGS: Analyzing the extent of the
      relationship between intimidation and medical errors will provide healthcare
      organizations and professionals with a foundation for the development of
      strategies to combat the effects of intimidation on medical errors and patient
      safety. CONCLUSIONS: The necessity to create a culture of safety in healthcare
      settings is paramount.

PMID- 20137025
TI  - Health and vulnerability in a time of economic uncertainty.

PMID- 20137026
TI  - The textual organization of placement into long-term care: issues for older
      adults with mental illness.
AB  - Arranging placement of older adults from hospital mental health units into
      nursing homes or assisted living facilities can be difficult and protracted. The
      difficulty in placing these individuals is often attributed to stigma; that is,
      personnel in nursing homes are reluctant to accept mentally ill older adults
      because of the fear of mental illness and violence. Using an institutional
      ethnographic approach, we argue the importance of exploring how nursing home
      access is organized, especially the institutional process of placement. Our
      study, examining the process of placing older adults from mental health units
      into nursing homes or assisted living facilities within a western Canadian city,
      reveals how three specific textual points within the institutional process of
      placement do not work well for older adults with mental illness. These textual
      points include: constructing the older adult as a 'placeable' person, the first
      level match and the second-level match. After exploring why the three specific
      points in the process do not work well for mentally ill individuals, we
      reconsider the explanation of stigma, and then suggest implications for change.

PMID- 20137027
TI  - Power in telephone-advice nursing.
AB  - Power is a central aspect of nursing, especially in telephone-advice nursing,
      where nurses assess callers' medical problems and decide what measures that need
      to be taken. This article presents a framework for understanding how power
      operates in social interaction between nurses and callers in telephone-advice
      nursing in primary care in Sweden. Power is analysed as the result of nurses and
      callers being oriented to five social structures that are relevant to their
      actions in this context, namely the organization of telephone-advice nursing, the
      social stock of medical knowledge, the professional division of labour between
      nurses and doctors, structures of social interaction and structures of emotions.
      While structural constraints govern some actions to a high degree, calls take
      place in an organizational free room that give nurses more leeway for acting more
      creatively. The discussion focuses on the introduction of new technologies of
      control, for instance computerized decision support systems and audio recording
      of calls, and on how they reduce the free room. Empirical data consist of 276
      audio-recorded telephone calls to 13 nurses at six primary-care centres and of
      qualitative interviews with 18 nurses.

PMID- 20137028
TI  - Public health nursing practice with 'high priority' families: the significance of
      contextualizing 'risk'.
AB  - Public health nurses (PHNs) play a vital role in supporting families at risk; few
      studies, however, have focused on how PHNs actually work with families to provide
      support, build trust, and use their clinical judgment to make decisions in
      complex, at-risk situations. In this study, we report on findings from research
      that illustrate how PHNs use relational approaches in their work with 'high
      priority' families. Drawing on data collected from interviews and focus groups
      with 32 PHNs, we discuss three central features inherent to working relationally
      with families at risk: (i) contextualizing the complexities of families' lives;
      (ii) responding to shifting contexts of risk and capacity; and (iii) working
      relationally with families under surveillance. These findings show that the
      ability to recognize risk and capacity as intersecting aspects of families'
      lives, and to practice from a stance that recognizes risk as contextualized is
      foundational to effective working relationships with high-priority families.

PMID- 20137029
TI  - Dealing with the patient's body in nursing: nurses' ambiguous experience in
      clinical practice.
AB  - The core of nursing in western countries is interaction with the patient and with
      his/her body in particular. As all nursing practices revolve around caring for
      the patient's body, nurses need to understand the frailty of the body, the
      intimacy surrounding it, the story it tells, as well as the discomfort and
      difficulties both illness and close contact can generate in the nurse-patient
      relationship. With this study, we wanted to explore the ward experiences of a
      small group of nurses in their day-to-day interaction with patients and their
      bodies, to highlight their perceptions and possible difficulties in providing
      care. We collected qualitative data from in-depth interviews with 14 nurses
      working in departments of general internal medicine, neurology, and geriatrics.
      The interviews were conducted between April and June 2006 and interpreted using
      an interpretive phenomenological approach. Analysis of the interview transcripts
      revealed that while the nurses recognize the centrality of the body in nursing,
      they also expressed a certain ambiguity toward it: being able to improve a
      patient's well-being through attentive care to the body is a major source of job
      satisfaction, but various coping and defense strategies are deployed to overcome
      care-giving situations that elicit avoidance or refusal reactions to the
      patient's body.

PMID- 20137030
TI  - Intervention to enhance empowerment in breast cancer self-help groups.
AB  - As arduous psychological reactions and loss of control almost inevitably
      represent a challenge for women diagnosed and treated for breast cancer, a
      participatory intervention study was initiated that aimed to enhance empowerment
      in breast cancer self-help groups. Women newly diagnosed with breast cancer were
      invited to participate. The intervention encompassed three professionally led
      self-help groups running sequentially, each group for approximately 4 months.
      Each group of five to seven participants met weekly. Several empowerment
      strategies were initiated by two professional facilitators, aiming to promote
      empowerment processes and to manage stress. The participants experienced group
      participation as both empowering and as a valuable source of support, and
      although the group processes developed very differently, a strong sense of
      fellowship developed in all three groups. The discussion highlights the findings
      in relation to several theoretical perspectives including social capital, social
      cohesion, risky agreements, helper-therapy and power/empowerment. We conclude
      that empowerment strategies that are implemented in professionally led breast
      cancer self-help groups can contribute to participant empowerment and function as
      an important source of re-discovery and confirmation of the participants'
      strengths and abilities.

PMID- 20137031
TI  - An exploration of ruling relations and how they organize and regulate nursing
      education in the high-fidelity patient simulation laboratory.
AB  - Recently, schools of nursing have adopted the use of high-fidelity human patient
      simulators in laboratory settings to teach nursing. Although numerous articles
      document the benefits of teaching undergraduate nursing students in this way,
      little attention has been paid to the discourses and texts organizing this
      approach. This institutional ethnography uses the critical feminist sociology of
      Dorothy E. Smith to examine the literature and interviews with Practical and
      Bachelor of Science in Nursing students, and their faculty about this experience.
      The research shows how discourses rationalize and sustain certain processes at
      the expense of others. For example, ruling discourses such as biomedicine,
      efficiency, and the relational ontology are activated to construct the simulation
      lab as part of nursing and nursing education. The analysis also highlights the
      intended and unintended effects of these discourses on nursing education and
      discusses how emphasizing nursing knowledges can make the simulation lab a
      positive place for learning.

PMID- 20137032
TI  - A review of empathy education in nursing.
AB  - The ability for nurse educators to improve the empathy skill set of nurses has
      been the subject of several studies with varied outcomes. The aim of this paper
      is to review the evidence for empathy education programmes in nursing and make
      recommendations for future nurse education. A review of CINAHL, Medline, Psych
      Info and Google Scholar was undertaken using the keywords empathy, person
      centredness, patient centredness, client centredness, education and nursing. The
      studies included were required to have measured the effectiveness of empathy
      training in postgraduate and or undergraduate nurses. The included studies
      incorporated both qualitative and quantitative methods and were published in peer
      reviewed journals. Studies were ranked for level of evidence according to The
      Joanna Briggs Institute criteria. Seventeen studies from the literature review
      were found that met the inclusion criteria. Of the 17 studies, 11 reported
      statistically significant improvements in empathy scores versus six studies that
      did not. Several variables may affect empathy education that need to be accounted
      in future studies such as; gender, cultural values and clinical speciality
      experience. Models of education that show most promise are those that use
      experiential styles of learning. The studies reviewed demonstrated that it is
      possible to increase nurses' empathic ability.

PMID- 20137033
TI  - Hermeneutics and observation--a discussion.
AB  - This study deals with hermeneutics and observation. The purpose is to discuss
      some central concerns of hermeneutics in relation to observation as a research
      method. Attention is centred on the hermeneutic process, preunderstanding,
      understanding, sensitivity, the fore-conception of completeness and language.
      Examples from an observation study are presented. The study ends with a
      discussion of the importance of proceeding without haste and of silence in
      observational hermeneutic research. The researcher must allow oneself to be
      influenced by these qualities if the observations are to be undertaken in a
      hermeneutic spirit. Physical time must be of lesser importance than inner time.
      The possibility then exists for the researcher to wander the hermeneutic spiral
      to the greatest depth possible.

PMID- 20137034
TI  - 'Everybody expects the perfect baby...and perfect labour...and so you have to
      protect yourself ': discourses of defence in midwifery practice in Aotearoa/New
      Zealand.
AB  - Increasing fears of litigation among those involved in childbirth impact
      differently on the 40 midwives I interviewed and observed in the field during the
      course of my doctoral research. 'Defensive practice' within a culture of 'risk'
      was a theme that emerged strongly from the interview transcript data from this
      study, the primary aim of which was to analyse the actions between women and
      midwives that constitute midwifery partnerships. The context for the analysis was
      a large ethnographic study undertaken with a variety of midwives working in a
      main city in Aotearoa/New Zealand in 2003. Complex and contesting forms of
      knowledge production were analysed drawing on insights from Foucauldian
      influenced discourse analysis. My work highlights the ways in which the practices
      of contemporary midwives in Aotearoa/New Zealand are caught within the
      intersection of an array of competing discourses. In the data from my study, the
      midwives talked of their complex negotiations of time and space, and their
      abilities to balance elements of risk within realms of restraint and
      responsibility in partnership with women. For the midwives I interviewed,
      'keeping ourselves safe' takes place in different locations. Risk is located by
      some midwives as within the birthing body, and by some, within the spaces of
      labour ward itself. Both labouring bodies in the midwifery partnership, however,
      that of the pregnant body of the woman, and that of the working body of the
      midwife, together occupy spaces of risk/safety where they are amenable to
      various, and increasingly subtle, forms of governance.

PMID- 20137035
TI  - Of pandemics and risk.

PMID- 20137036
TI  - Comments on shaken baby syndrome.

PMID- 20137037
TI  - Comments on shaken baby syndrome.

PMID- 20137038
TI  - Urinary catheterization during epidural anesthesia.

PMID- 20137040
TI  - Perinatal depression: a health marketing campaign to improve screening.

PMID- 20137041
TI  - It does matter: breast cancer is the second leading cause of cancer deaths in
      American women (American Cancer Society, 2008). Assuming an average life span of
      85 years, one in eight U.S. women will be diagnosed with breast cancer.

PMID- 20137042
TI  - Successful nurse engagement: one health care system's story .

PMID- 20137043
TI  - Cultural competence: nursing in a multicultural society.

PMID- 20137044
TI  - Bottle/Nipple systems: helping parents make informed choices.

PMID- 20137045
TI  - Systematic reviews: strong evidence on which to base practice.

PMID- 20137046
TI  - Communicating risk: rationale and strategies.

PMID- 20137049
TI  - Confidentiality in adolescent health care.

PMID- 20137050
TI  - HPV vaccination for the prevention of cervical cancer.

PMID- 20137051
TI  - Universal screening for hyperbilirubinemia.

PMID- 20137052
TI  - A challenging birth experience.

PMID- 20137053
TI  - Nutritional approach to sun protection: a suggested complement to external
      strategies.
AB  - The increasing incidence of skin cancer despite the use of externally applied sun
      protection strategies, alongside research showing that nutrients reduce photo
      oxidative damage, suggest nutritional approaches could play a beneficial role in
      skin cancer prevention. Penetrating photo-oxidative ultraviolet A radiation
      reduces skin and blood antioxidants and damages cell components, including DNA.
      Dietary antioxidant vitamins, minerals, and phytochemicals in addition to n-3
      polyunsaturated fatty acids, n-9 monounsaturated fatty acids, and low pro
      inflammatory n-6 polyunsaturated fatty acids, have demonstrated protective
      properties. The presence of these elements in the traditional Greek-style
      Mediterranean diet may have contributed to the low rates of melanoma in the
      Mediterranean region despite high levels of solar radiation. This suggests a
      potentially relevant model for studying dietary/nutritional supplementation for
      lifelong internal support of sun-protection mechanisms, which could complement
      external strategies.

PMID- 20137054
TI  - Fetal programming: link between early nutrition, DNA methylation, and complex
      diseases.
AB  - Complex traits, including those involved in diet-related diseases, are determined
      by multiple genes and environmental influences. Factors influencing the
      development of complex traits should be expanded to include epigenetic factors,
      such as DNA methylation, which occurs in utero. Epigenetic factors regulate gene
      expression and thereby cell differentiation and organogenesis. The process of
      epigenotype establishment is sensitive to environmental conditions, with
      nutrition being one of the most important related factors. For example, DNA
      methylation depends on the availability of several nutrients including methionine
      and vitamins B(6), B(12), and folate. Epidemiological studies show that
      undernutrition during fetal life is associated with increased susceptibility to
      complex diseases. Numerous studies have been conducted on prenatal caloric and
      protein undernutrition. A reduction in the number of cells and changes in the
      structure and functioning of organs, as well as permanent changes in DNA
      methylation and gene expression, have been considered the molecular mechanisms
      responsible for metabolism programming.

PMID- 20137055
TI  - Folate-mediated one-carbon metabolism and its effect on female fertility and
      pregnancy viability.
AB  - This review summarizes current knowledge of the effect of folate-mediated one
      carbon metabolism and related genetic variants on female fertility and pregnancy
      viability. Insufficient folate status disrupts DNA methylation and integrity and
      increases blood homocysteine levels. Elevated levels of follicular fluid
      homocysteine correlate with oocyte immaturity and poor early embryo quality,
      while methylenetetrahydrofolate reductase (MTHFR) gene variants are associated
      with lower ovarian reserves, diminished response to follicular stimulation, and
      reduced chance of live birth after in vitro fertilization. Embryos carrying
      multiple MTHFR variants appear to have a selective disadvantage; however, the
      heterozygous MTHFR 677CT genotype in the mother and fetus provides the greatest
      chance for a viable pregnancy and live birth, possibly due to a favorable balance
      in folate cofactor distribution between methyl donor and nucleotide synthesis.
      The results of previous studies clearly emphasize that imbalances in folate
      metabolism and related gene variants may impair female fecundity as well as
      compromise implantation and the chance of a live birth.

PMID- 20137056
TI  - How the US Food and Drug Administration evaluates the scientific evidence for
      health claims.
AB  - Health claims describe the relationship between a substance (food or component of
      food) and a disease or health-related condition. They were first authorized
      through the Nutrition Labeling and Education Act of 1990. The standard set by the
      US Congress for the scientific evidence required to authorize a claim was the
      significant scientific agreement standard. This strong standard was challenged by
      several manufacturers of dietary supplements. Several court decisions directed
      the US Food and Drug Administration (FDA) to provide for dietary supplement
      claims not meeting the significant scientific agreement standard by adding a
      disclaimer to the claim that would eliminate the claim's potential to be
      misleading. In December 2002, the FDA announced a major new initiative, "The
      Consumer Health Information for Better Nutrition Initiative," which, among other
      things, provided for the use of qualified health claims for both conventional
      foods and dietary supplements. The process for reviewing the scientific evidence
      for a claim reaching significant scientific agreement and for those that require
      qualifying language is the same. In January 2009, the FDA issued a guidance
      document entitled "Evidence-Based Review System for the Scientific Evaluation of
      Health Claims." The process used by the FDA to review the scientific evidence for
      health claims and qualified health claims are described in this article.

PMID- 20137057
TI  - Pomegranate and breast cancer: possible mechanisms of prevention.
AB  - Several mechanistic studies in cell culture and mouse models suggest possible
      estrogen receptor-mediated and non-estrogen receptor-mediated benefits of
      pomegranate juice with respect to breast cancer risk. These studies demonstrate
      that various constituents of pomegranates can inhibit aromatase and 17beta
      hydroxysteroid dehydrogenase enzymes or have antiestrogenic activity. Additional
      large, well-controlled human studies are warranted to elucidate the effects of
      pomegranate juice intake on serum hormone levels. Clarifying the effects of
      pomegranate constituents on key hormones known to be involved in breast cancer
      could result in important information for consumers and shed further light on the
      impact of diet on breast cancer risk.

PMID- 20137059
TI  - Multicentre study on standardisation of melanoma cell culture--an initiative of
      the German Melanoma Research Network.

PMID- 20137060
TI  - Consequences of nitric oxide synthase inhibition during bovine oocyte maturation
      on meiosis and embryo development.
AB  - The importance of nitric oxide synthase (NOS) in bovine oocyte maturation was
      investigated. Oocytes were in vitro matured with the NOS inhibitor N(w)-L-nitro
      arginine methyl-ester (10(-7), 10(-5) and 10(-3) m L-NAME) and metaphase II (MII)
      rates and embryo development and quality were assessed. The effect of L-NAME (10(
      7) m) during pre-maturation and/or maturation on embryo development and quality
      was also assessed. L-NAME decreased MII rates (78-82%, p < 0.05) when compared
      with controls without L-NAME (96%). Cleavage (77-88%, p > 0.05), Day 7 blastocyst
      rates (34-42%, p > 0.05) and total cell numbers in blastocysts were similar for
      all groups (146-171 cells, p > 0.05). Day 8 blastocyst TUNEL positive cells (3-4
      cells) increased with L-NAME treatment (p < 0.05). For oocytes cultured with L
      NAME during pre-maturation and/or maturation, Day 8 blastocyst development (26
      34%) and Day 9 hatching rates (15-22%) were similar (p > 0.05) to controls pre
      matured and matured without NOS inhibition (33 and 18%, respectively), while
      total cell numbers (Day 9 hatched blastocysts) increased (264-324 cells, p <
      0.05) when compared with the controls (191 cells). TUNEL positive cells increased
      when NOS was inhibited only during the maturation period (8 cells, p < 0.05) when
      compared with the other groups (3-4 cells). NO may be involved in meiosis
      progression to MII and its deficiency during maturation increases apoptosis in
      embryos produced in vitro. Nitric oxide synthase inhibition during pre-maturation
      and/or maturation affects embryo quality.

PMID- 20137061
TI  - Effect of alpha-tocopherol on bovine in vitro fertilization.
AB  - The objectives of this work are to determine if exogenous supplementation with
      alpha-tocopherol increases the in vitro fertilization (IVF) rate of bovine
      oocytes and improves viability of selected spermatozoa after 'swim-up'. The
      percentage of fertilized oocytes was significantly but negatively correlated (r =
      -0.941, p < 0.01) with the concentration of alpha-tocopherol. The control
      resulted in 95% of fertilized oocytes, which decreased as follows: 25 microM
      alpha-tocopherol (alpha25) 86%, 50 microM alpha-tocopherol (alpha50) 74%, 100
      microM alpha-tocopherol (alpha100) 66% and 200 microM alpha-tocopherol (alpha200)
      56%. Relatively to sperm viability after 'swim-up' with alpha-tocopherol
      supplementation, this antioxidant proved to have a beneficial effect as its
      concentration increased up to alpha50, decreasing for the concentrations of
      alpha100 and alpha200. Control resulted in 83% of live cells and 16% of dead
      cells; alpha25 resulted in 88% of live cells and 12% of dead cells; alpha50
      resulted in 91% of live cells and 9% of dead cells; alpha100 resulted in 67% of
      live cells and 33% of dead cells; and finally alpha200 resulted in 57% of live
      cells and 42% of dead cells. In summary, the present study allows to conclude
      that, in our conditions, supplementation with the antioxidant alpha-tocopherol in
      IVF of bovine oocytes has a detrimental effect on fertilization rates.
      Nevertheless, exogenous supplementation with alpha-tocopherol at a concentration
      of 50 mM in the sperm-TALP media during the 'swim-up' technique has a significant
      beneficial effect on the selected spermatozoa viability.

PMID- 20137062
TI  - Abstracts of the 43rd Annual Conference of Physiology and Pathology of
      Reproduction and 35th Mutual Conference on Veterinary and Human Reproductive
      Medicine. Munich, Germany. February 24-26, 2010.

PMID- 20137063
TI  - The long-term effects of naprapathic manual therapy on back and neck pain -
      results from a pragmatic randomized controlled trial.
AB  - BACKGROUND: Back and neck pain are very common, disabling and recurrent disorders
      in the general population and the knowledge of long-term effect of treatments are
      sparse. The aim of this study was to compare the long-term effects (up to one
      year) of naprapathic manual therapy and evidence-based advice on staying active
      regarding non-specific back and/or neck pain. Naprapathy, a health profession
      mainly practiced in Sweden, Finland, Norway and in the USA, is characterized by a
      combination of manual musculoskeletal manipulations, aiming to decrease pain and
      disability in the neuromusculoskeletal system. METHODS: Subjects with non
      specific pain/disability in the back and/or neck lasting for at least two weeks
      (n = 409), recruited at public companies in Sweden, were included in this
      pragmatic randomized controlled trial. The two interventions compared were
      naprapathic manual therapy such as spinal manipulation/mobilization, massage and
      stretching, (Index Group), and advice to stay active and on how to cope with
      pain, provided by a physician (Control Group). Pain intensity, disability and
      health status were measured by questionnaires. RESULTS: 89% completed the 26-week
      follow-up and 85% the 52-week follow-up. A higher proportion in the Index Group
      had a clinically important decrease in pain (risk difference (RD) = 21%, 95% CI:
      10-30) and disability (RD = 11%, 95% CI: 4-22) at 26-week, as well as at 52-week
      follow-ups (pain: RD = 17%, 95% CI: 7-27 and disability: RD = 17%, 95% CI: 5-28).
      The differences between the groups in pain and disability considered over one
      year were statistically significant favoring naprapathy (p < or = 0.005). There
      were also significant differences in improvement in bodily pain and social
      function (subscales of SF-36 health status) favoring the Index Group.
      CONCLUSIONS: Combined manual therapy, like naprapathy, is effective in the short
      and in the long term, and might be considered for patients with non-specific back
      and/or neck pain. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56954776.

PMID- 20137064
TI  - Microglial responses around intrinsic CNS neurons are correlated with axonal
      regeneration.
AB  - BACKGROUND: Microglia/macrophages and lymphocytes (T-cells) accumulate around
      motor and primary sensory neurons that are regenerating axons but there is little
      or no microglial activation or T-cell accumulation around axotomised intrinsic
      CNS neurons, which do not normally regenerate axons. We aimed to establish
      whether there was an inflammatory response around the perikarya of CNS neurons
      that were induced to regenerate axons through a peripheral nerve graft. RESULTS:
      When neurons of the thalamic reticular nucleus (TRN) and red nucleus were induced
      to regenerate axons along peripheral nerve grafts, a marked microglial response
      was found around their cell bodies, including the partial enwrapping of some
      regenerating neurons. T-cells were found amongst regenerating TRN neurons but not
      rubrospinal neurons. Axotomy alone or insertion of freeze-killed nerve grafts did
      not induce a similar perineuronal inflammation. Nerve grafts in the corticospinal
      tracts did not induce axonal regeneration or a microglial or T-cell response in
      the motor cortex. CONCLUSIONS: These results strengthen the evidence that
      perineuronal microglial accumulation (but not T-cell accumulation) is involved in
      axonal regeneration by intrinsic CNS and other neurons.

PMID- 20137065
TI  - Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole.
AB  - BACKGROUND: Pramipexole exists as two isomers. The S(-) enantiomer is a potent
      D3/D2 receptor agonist and is extensively used in the management of PD. In
      contrast, the R(+) enantiomer is virtually devoid of any of the DA agonist
      effects. Very limited studies are available to characterize the pharmacological
      spectrum of the R(+) enantiomer of pramipexole. RESULTS: Using differentiated SH
      SY5Y neuroblastoma cells as an experimental model, here we show that S(-) and
      R(+) pramipexole are endowed with equipotent efficacy in preventing cell death
      induced by H2O2 and inhibiting mitochondrial reactive oxygen species generation.
      Both pramipexole enantiomers prevented mitochondrial ROS generation with a
      potency about ten times higher then that elicited for neuroprotection.
      CONCLUSIONS: These results support the concept of both S(-) and R(+) pramipexole
      enantiomers as mitochondria-targeted antioxidants and suggest that the
      antioxidant, neuroprotective activity of these drugs is independent of both the
      chiral 6-propylamino group in the pramipexole molecule and the DA receptor
      stimulation.

PMID- 20137066
TI  - Transcriptional response of Burkholderia cenocepacia J2315 sessile cells to
      treatments with high doses of hydrogen peroxide and sodium hypochlorite.
AB  - BACKGROUND: Burkholderia cepacia complex bacteria are opportunistic pathogens,
      which can cause severe respiratory tract infections in patients with cystic
      fibrosis (CF). As treatment of infected CF patients is problematic, multiple
      preventive measures are taken to reduce the infection risk. Besides a stringent
      segregation policy to prevent patient-to-patient transmission, clinicians also
      advise patients to clean and disinfect their respiratory equipment on a regular
      basis. However, problems regarding the efficacy of several disinfection
      procedures for the removal and/or killing of B. cepacia complex bacteria have
      been reported. In order to unravel the molecular mechanisms involved in the
      resistance of biofilm-grown Burkholderia cenocepacia cells against high
      concentrations of reactive oxygen species (ROS), the present study focussed on
      the transcriptional response in sessile B. cenocepacia J2315 cells following
      exposure to high levels of H2O2 or NaOCl. RESULTS: The exposure to H2O2 and NaOCl
      resulted in an upregulation of the transcription of 315 (4.4%) and 386 (5.4%)
      genes, respectively. Transcription of 185 (2.6%) and 331 (4.6%) genes was
      decreased in response to the respective treatments. Many of the upregulated genes
      in the NaOCl- and H2O2-treated biofilms are involved in oxidative stress as well
      as general stress response, emphasizing the importance of the efficient
      neutralization and scavenging of ROS. In addition, multiple upregulated genes
      encode proteins that are necessary to repair ROS-induced cellular damage.
      Unexpectedly, a prolonged treatment with H2O2 also resulted in an increased
      transcription of multiple phage-related genes. A closer inspection of
      hybridisation signals obtained with probes targeting intergenic regions led to
      the identification of a putative 6S RNA. CONCLUSION: Our results reveal that the
      transcription of a large fraction of B. cenocepacia J2315 genes is altered upon
      exposure of sessile cells to ROS. These observations have highlighted that B.
      cenocepacia may alter several pathways in response to exposure to ROS and they
      have led to the identification of many genes not previously implicated in the
      stress response of this pathogen.

PMID- 20137067
TI  - FOXP3 and GARP (LRRC32): the master and its minion.
AB  - The transcription factor FOXP3 is essential for the development and function of
      CD4+CD25hiFOXP3+ regulatory T (T(reg)) cells, but also expressed in activated
      human helper T cells without acquisition of a regulatory phenotype. This comment
      focuses on glycoprotein-A repetitions predominant (GARP or LRRC32) recently
      identified as specific marker of activated human T(reg) cells, which may provide
      the missing link toward a better molecular definition of the regulatory
      phenotype.

PMID- 20137069
TI  - Association between framing of the research question using the PICOT format and
      reporting quality of randomized controlled trials.
AB  - BACKGROUND: Experts recommend formulating a structured research question to guide
      the research design. However, the basis for this recommendation has not been
      formally evaluated. The aim of this study was to examine if a structured research
      question using the PICOT (Population, Intervention, Comparator, Outcome, Time
      frame) format is associated with a better reporting quality of randomized
      controlled trials (RCTs). METHODS: We evaluated 89 RCTs reports published in
      three endocrinology journals in 2005 and 2006, the quality of reporting of which
      was assessed in a previous study. We examined whether the reports stated each of
      the five elements of a structured research question: population, intervention,
      comparator, outcome and time-frame. A PICOT score was created with a possible
      score between 0 and 5. Outcomes were: 1) a 14-point overall reporting quality
      score (OQS) based on the Consolidated Standards for Reporting Trials; and 2) a 3
      point key score (KS), based on allocation concealment, blinding and use of
      intention-to-treat analysis. We conducted multivariable regression analyses using
      generalized estimating equations to determine if a higher PICOT score or the use
      of a structured research question were independently associated with a better
      reporting quality. Journal of publication, funding source and sample size were
      identified as factors associated with OQS in our previous report on this dataset,
      and therefore included in the model. RESULTS: A higher PICOT score was
      independently associated with OQS (incidence rate ratio (IRR) = 1.021, 95% CI:
      1.012 to 1.029) and KS (IRR = 1.142, 95% CI: 1.079 to 1.210). A structured
      research question was present in 33.7% of the reports and it was associated with
      a better OQS (IRR = 1.095, 95% CI 1.059-1.132) and KS (IRR = 1.530, 95% CI 1.311
      1.786). CONCLUSIONS: Better framing of the research question using the PICOT
      format is independently associated with better overall reporting quality -
      although the effect is small - and better reporting of key methodologies.

PMID- 20137068
TI  - Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte
      lineage maturation.
AB  - BACKGROUND: Long non-protein-coding RNAs (ncRNAs) are emerging as important
      regulators of cellular differentiation and are widely expressed in the brain.
      RESULTS: Here we show that many long ncRNAs exhibit dynamic expression patterns
      during neuronal and oligodendrocyte (OL) lineage specification, neuronal-glial
      fate transitions, and progressive stages of OL lineage elaboration including
      myelination. Consideration of the genomic context of these dynamically regulated
      ncRNAs showed they were part of complex transcriptional loci that encompass key
      neural developmental protein-coding genes, with which they exhibit concordant
      expression profiles as indicated by both microarray and in situ hybridization
      analyses. These included ncRNAs associated with differentiation-specific nuclear
      subdomains such as Gomafu and Neat1, and ncRNAs associated with developmental
      enhancers and genes encoding important transcription factors and homeotic
      proteins. We also observed changes in ncRNA expression profiles in response to
      treatment with trichostatin A, a histone deacetylase inhibitor that prevents the
      progression of OL progenitors into post-mitotic OLs by altering lineage-specific
      gene expression programs. CONCLUSION: This is the first report of long ncRNA
      expression in neuronal and glial cell differentiation and of the modulation of
      ncRNA expression by modification of chromatin architecture. These observations
      explicitly link ncRNA dynamics to neural stem cell fate decisions, specification
      and epigenetic reprogramming and may have important implications for
      understanding and treating neuropsychiatric diseases.

PMID- 20137070
TI  - The association between leukocytes and sperm quality is concentration dependent.
AB  - BACKGROUND: To evaluate the association between leukocytes (polymorphonuclear
      granulocytes -PMNL) and semen parameters at different leukocyte concentrations.
      METHODS: This was a retrospective clinical study at a university hospital
      andrology clinic. Semen samples from infertile men were analyzed for sperm
      morphology and motility according to seminal leukocytes (PMNL) concentration
      (category A: >0 to <0.25 x 10(6)/mL; category B: >0.25 to <0.5 x 10(6)/mL;
      category C: >0.5 to <0.75 x 10(6)/mL; category D: >0.75 to <1.0 x 10(6)/mL,
      category E: >1 x 10(6)/mL). RESULTS: The percentage of sperm with normal
      morphology increased significantly from category A (14%) to category D (19%) but
      decreased in category E to levels (14%) similar to those in category A. Motility
      grades a and a+b (combined) also increased from category A (12%, 20%) to category
      D (18.0%, 28.5%) and decreased in category E (11%, 20.5%) to levels similar to
      those in category A. Sperm deformities and motility grades c and d increased
      progressively in all categories. SUMMARY: Leukocytes had a positive association
      with normal morphology and progressive motility in semen samples at a
      concentration of 0-1 x 10(6)/mL. The findings suggest that the association
      between leukocytes (PMNL) and semen quality might be concentration dependent.

PMID- 20137071
TI  - A scalable, fully automated process for construction of sequence-ready barcoded
      libraries for 454.
AB  - We present an automated, high throughput library construction process for 454
      technology. Sample handling errors and cross-contamination are minimized via end
      to-end barcoding of plasticware, along with molecular DNA barcoding of
      constructs. Automation-friendly magnetic bead-based size selection and cleanup
      steps have been devised, eliminating major bottlenecks and significant sources of
      error. Using this methodology, one technician can create 96 sequence-ready 454
      libraries in 2 days, a dramatic improvement over the standard method.

PMID- 20137072
TI  - Complete genome sequence and lifestyle of black-pigmented Corynebacterium
      aurimucosum ATCC 700975 (formerly C. nigricans CN-1) isolated from a vaginal swab
      of a woman with spontaneous abortion.
AB  - BACKGROUND: Corynebacterium aurimucosum is a slightly yellowish, non-lipophilic,
      facultative anaerobic member of the genus Corynebacterium and predominantly
      isolated from human clinical specimens. Unusual black-pigmented variants of C.
      aurimucosum (originally named as C. nigricans) continue to be recovered from the
      female urogenital tract and they are associated with complications during
      pregnancy. C. aurimucosum ATCC 700975 (C. nigricans CN-1) was originally isolated
      from a vaginal swab of a 34-year-old woman who experienced a spontaneous abortion
      during month six of pregnancy. For a better understanding of the physiology and
      lifestyle of this potential urogenital pathogen, the complete genome sequence of
      C. aurimucosum ATCC 700975 was determined. RESULTS: Sequencing and assembly of
      the C. aurimucosum ATCC 700975 genome yielded a circular chromosome of 2,790,189
      bp in size and the 29,037-bp plasmid pET44827. Specific gene sets associated with
      the central metabolism of C. aurimucosum apparently provide enhanced metabolic
      flexibility and adaptability in aerobic, anaerobic and low-pH environments,
      including gene clusters for the uptake and degradation of aromatic amines, L
      histidine and L-tartrate as well as a gene region for the formation of
      selenocysteine and its incorporation into formate dehydrogenase. Plasmid pET44827
      codes for a non-ribosomal peptide synthetase that plays the pivotal role in the
      synthesis of the characteristic black pigment of C. aurimucosum ATCC 700975.
      CONCLUSIONS: The data obtained by the genome project suggest that C. aurimucosum
      could be both a resident of the human gut and possibly a pathogen in the female
      genital tract causing complications during pregnancy. Since hitherto all black
      pigmented C. aurimucosum strains have been recovered from female genital source,
      biosynthesis of the pigment is apparently required for colonization by protecting
      the bacterial cells against the high hydrogen peroxide concentration in the
      vaginal environment. The location of the corresponding genes on plasmid pET44827
      explains why black-pigmented (formerly C. nigricans) and non-pigmented C.
      aurimucosum strains were isolated from clinical specimens.

PMID- 20137073
TI  - Ceramide and ceramide 1-phosphate in health and disease.
AB  - Sphingolipids are essential components of cell membranes, and many of them
      regulate vital cell functions. In particular, ceramide plays crucial roles in
      cell signaling processes. Two major actions of ceramides are the promotion of
      cell cycle arrest and the induction of apoptosis. Phosphorylation of ceramide
      produces ceramide 1-phosphate (C1P), which has opposite effects to ceramide. C1P
      is mitogenic and has prosurvival properties. In addition, C1P is an important
      mediator of inflammatory responses, an action that takes place through
      stimulation of cytosolic phospholipase A2, and the subsequent release of
      arachidonic acid and prostaglandin formation. All of the former actions are
      thought to be mediated by intracellularly generated C1P. However, the recent
      observation that C1P stimulates macrophage chemotaxis implicates specific plasma
      membrane receptors that are coupled to Gi proteins. Hence, it can be concluded
      that C1P has dual actions in cells, as it can act as an intracellular second
      messenger to promote cell survival, or as an extracellular receptor agonist to
      stimulate cell migration.

PMID- 20137074
TI  - Identification of arginine- and lysine-methylation in the proteome of
      Saccharomyces cerevisiae and its functional implications.
AB  - BACKGROUND: The methylation of eukaryotic proteins has been proposed to be
      widespread, but this has not been conclusively shown to date. In this study, we
      examined 36,854 previously generated peptide mass spectra from 2,607
      Saccharomyces cerevisiae proteins for the presence of arginine and lysine
      methylation. This was done using the FindMod tool and 5 filters that took
      advantage of the high number of replicate analysis per protein and the presence
      of overlapping peptides. RESULTS: A total of 83 high-confidence lysine and
      arginine methylation sites were found in 66 proteins. Motif analysis revealed
      many methylated sites were associated with MK, RGG/RXG/RGX or WXXXR motifs.
      Functionally, methylated proteins were significantly enriched for protein
      translation, ribosomal biogenesis and assembly and organellar organisation and
      were predominantly found in the cytoplasm and ribosome. Intriguingly, methylated
      proteins were seen to have significantly longer half-life than proteins for which
      no methylation was found. Some 43% of methylated lysine sites were predicted to
      be amenable to ubiquitination, suggesting methyl-lysine might block the action of
      ubiquitin ligase. CONCLUSIONS: This study suggests protein methylation to be
      quite widespread, albeit associated with specific functions. Large-scale tandem
      mass spectroscopy analyses will help to further confirm the modifications
      reported here.

PMID- 20137075
TI  - Mapping of hormones and cortisol responses in patients after Lyme
      neuroborreliosis.
AB  - BACKGROUND: Persistent symptoms after treatment for neuroborreliosis are common
      for reasons mainly unknown. These symptoms are often unspecific and could be
      caused by dysfunctions in endocrine systems, an issue that has not been
      previously addressed systematically. We therefore mapped hormone levels in
      patients with previous confirmed Lyme neuroborreliosis of different outcomes and
      compared them with a healthy control group. METHODS: Twenty patients of a
      retrospective cohort of patients treated for definite Lyme neuroborreliosis were
      recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy
      controls. Lyme neuroborreliosis patients were stratified into two groups
      according to a symptom/sign score. All participants underwent anthropometric and
      physiological investigation as well as an extensive biochemical endocrine
      investigation including a short high-dose adrenocorticotropic hormone stimulation
      (Synacthen) test. In addition to hormonal status, we also examined electrolytes,
      25-hydroxy-vitamin D and interleukin-6. RESULTS: Eight patients (40%) had
      pronounced symptoms 2-3 years after treatment. This group had a higher cortisol
      response to synacthen as compared with both controls and the Lyme
      neuroborreliosis patients without remaining symptoms (p < 0.001 for both
      comparisons). No other significant differences in the various baseline
      biochemical parameters, anthropometric or physiological data could be detected
      across groups. CONCLUSIONS: Apart from a positive association between the
      occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol
      response to synacthen, no corticotropic insufficiency or other serious hormonal
      dysfunction was found to be associated with remaining symptoms after treatment
      for Lyme neuroborreliosis.

PMID- 20137076
TI  - Efficacy of Lactic Acid Bacteria (LAB) supplement in management of constipation
      among nursing home residents.
AB  - BACKGROUND: Constipation is a significant problem in the elderly, specifically
      nursing home and/or extended-care facility residents are reported to suffer from
      constipation. Lactic acid bacteria (LAB) are beneficial probiotic organisms that
      contribute to improved nutrition, microbial balance, and immuno-enhancement of
      the intestinal tract, as well as diarrhea and constipation effect. The objective
      of this study was to investigate the efficacy of this LAB supplement in the
      management of nursing home residents. METHODS: Nineteen subjects (8M, 11F; mean
      age 77.1 +/- 10.1) suffering with chronic constipation were assigned to receive
      LAB (3.0 x 10(11) CFU/g) twice (to be taken 30 minutes after breakfast and
      dinner) a day for 2 weeks in November 2008. Subjects draw up a questionnaire on
      defecation habits (frequency of defecation, amount and state of stool), and we
      collected fecal samples from the subjects both before entering and after ending
      the trial, to investigate LAB levels and inhibition of harmful enzyme activities.
      Results were tested with SAS and Student's t-test. RESULTS: Analysis of
      questionnaire showed that there was an increase in the frequency of defecation
      and amount of stool excreted in defecation habit after LAB treatment, but there
      were no significant changes. And it also affects the intestinal environment,
      through significantly increase (p < 0.05) fecal LAB levels. In addition,
      tryptophanase and urease among harmful enzyme activities of intestinal microflora
      were significantly decreased (p < 0.05) after LAB treatment. CONCLUSION: LAB,
      when added to the standard treatment regimen for nursing home residents with
      chronic constipation, increased defecation habit such as frequency of defecation,
      amount and state of stool. So, it may be used as functional probiotics to improve
      human health by helping to prevent constipation.

PMID- 20137077
TI  - Extracting consistent knowledge from highly inconsistent cancer gene data
      sources.
AB  - BACKGROUND: Hundreds of genes that are causally implicated in oncogenesis have
      been found and collected in various databases. For efficient application of these
      abundant but diverse data sources, it is of fundamental importance to evaluate
      their consistency. RESULTS: First, we showed that the lists of cancer genes from
      some major data sources were highly inconsistent in terms of overlapping genes.
      In particular, most cancer genes accumulated in previous small-scale studies
      could not be rediscovered in current high-throughput genome screening studies.
      Then, based on a metric proposed in this study, we showed that most cancer gene
      lists from different data sources were highly functionally consistent. Finally,
      we extracted functionally consistent cancer genes from various data sources and
      collected them in our database F-Census. CONCLUSIONS: Although they have very low
      gene overlapping, most cancer gene data sources are highly consistent at the
      functional level, which indicates that they can separately capture partial genes
      in a few key pathways associated with cancer. Our results suggest that the sample
      sizes currently used for cancer studies might be inadequate for consistently
      capturing individual cancer genes, but could be sufficient for finding a number
      of cancer genes that could represent functionally most cancer genes. The F-Census
      database provides biologists with a useful tool for browsing and extracting
      functionally consistent cancer genes from various data sources.

PMID- 20137078
TI  - Small RNA interference-mediated gene silencing of heparanase abolishes the
      invasion, metastasis and angiogenesis of gastric cancer cells.
AB  - BACKGROUND: Heparanase facilitates the invasion and metastasis of cancer cells,
      and is over-expressed in many kinds of malignancies. Our studies indicated that
      heparanase was frequently expressed in advanced gastric cancers. The aim of this
      study is to determine whether silencing of heparanase expression can abolish the
      malignant characteristics of gastric cancer cells. METHODS: Three heparanase
      specific small interfering RNA (siRNAs) were designed, synthesized, and
      transfected into cultured gastric cancer cell line SGC-7901. Heparanase
      expression was measured by RT-PCR, real-time quantitative PCR and Western blot.
      Cell proliferation was detected by MTT colorimetry and colony formation assay.
      The in vitro invasion and metastasis of cancer cells were measured by cell
      adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis
      capabilities of cancer cells were measured by tube formation of endothelial
      cells. RESULTS: Transfection of siRNA against 1496-1514 bp of encoding regions
      resulted in reduced expression of heparanase, which started at 24 hrs and lasted
      for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase
      suppressed the cellular proliferation of SGC-7901 cells. In addition, the in
      vitro invasion and metastasis of cancer cells were attenuated after knock-down of
      heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the in
      vitro angiogenesis of cancer cells in a dose-dependent manner. CONCLUSIONS: These
      results demonstrated that gene silencing of heparanase can efficiently abolish
      the proliferation, invasion, metastasis and angiogenesis of human gastric cancer
      cells in vitro, suggesting that heparanase-specific siRNA is of potential values
      as a novel therapeutic agent for human gastric cancer.

PMID- 20137079
TI  - Feasibility study to inform the design of a randomised controlled trial to
      eradicate Pseudomonas aeruginosa infection in individuals with cystic fibrosis.
AB  - BACKGROUND: There are controversies about the most effective treatment to
      eradicate first growth of Pseudomonas aeruginosa (P aeruginosa) from the lower
      airways of patients with cystic fibrosis (CF). UK guidelines recommend oral
      treatment, but some advocate intravenous (IV) treatment. The objective of this
      study was to assess the feasibility of conducting a randomised controlled trial
      comparing two treatment strategies to eradicate P aeruginosa in CF patients.
      METHODS/PRINCIPAL FINDINGS: Two surveys were conducted. Survey [1] included
      clinicians who were responsible for the treatment of individuals with CF, to
      assess their clinical practice, opinions and numbers of potentially eligible
      patients. Survey [2] included adults and young people aged 13 years or more with
      CF and parents of children with CF aged less than 13 years, identified at six UK
      CF centres, who fulfilled eligibility criteria for the proposed clinical trial,
      to assess their views about the interventions and their willingness to
      participate in the trial. Generally clinicians treat first or new growth of P
      aeruginosa with oral antibiotics, but 90% reported that they would consider IV
      treatment of first isolation of P aeruginosa. 74% of clinicians would consider
      recruiting their patients and 45% of consumers would consider entry for
      themselves or their children into a trial comparing oral with intravenous
      antibiotics. The median rate per annum for first or new growths of P aeruginosa
      in adults was 3% (range 1% to 9%) and in children was 10% (range 3% to 23%). If
      the trial was conducted across the UK, with a consent rate of 45%, then the
      number of eligible patients per annum who would be willing to take part in a
      study would be approximately 41 adults and 203 children. CONCLUSIONS: This work
      demonstrates the importance of feasibility studies in preparation for multicentre
      clinical trials. It confirmed the uncertainty amongst clinicians and patients
      about the clinical question, enabled assessment of the number of potentially
      eligible patients, the proportion of patients and clinicians prepared to
      participate and aspects of trial design which might encourage this. It showed
      that a clinical trial was feasible, but only if patients were recruited from
      across United Kingdom.

PMID- 20137080
TI  - Helicobacter pylori-induced activation of beta-catenin involves low density
      lipoprotein receptor-related protein 6 and Dishevelled.
AB  - BACKGROUND: The human microbial pathogen Helicobacter pylori resides in the
      stomach of about fifty percent of the world's population and represents a risk
      factor for chronic gastritis, peptic ulcers and, in rare cases, gastric cancer.
      Alterations of the Wnt/beta-catenin signaling pathway have been described in
      almost every human cancer disease, due to the regulation of target genes being
      involved in cell cycle control, differentiation, cell migration or stem cell
      control. Our study aimed to elucidate the role of proximal Wnt signaling
      components low density lipoprotein receptor-related protein 6 (LRP6) and
      Dishevelled (Dvl) in the activation of beta-catenin early after infection of
      gastric epithelial cells with H. pylori. RESULTS: Infection of gastric epithelial
      NCI-N87 cells with H. pylori induces rapid phosphorylation of the Wnt/beta
      catenin pathway co-receptor LRP6 independent of the cytotoxin-associated gene A
      (CagA) or vacuolating cytotoxin A (VacA). However, bacteria lacking a functional
      type 4 secretion system (T4SS) failed to induce LRP6 phosphorylation. Further, we
      identified proteins of the Dvl family, namely Dvl2 and Dvl3, which are involved
      in LRP6 phosphorylation. H. pylori-induced nuclear accumulation of beta-catenin
      and its transcriptional activation, and expression of Wnt target genes are
      strongly reduced in stable knockdown cell lines deficient for LRP6, Dvl2 or Dvl3.
      CONCLUSION: We analysed the H. pylori-induced activation of Wnt-signaling factors
      and demonstrate for the first time that the canonical Wnt-signaling proteins LRP6
      and Dvl2 and Dvl3 are involved in the regulation of beta-catenin.

PMID- 20137081
TI  - Low level of polymorphism in two putative NPR1 homologs in the Vitaceae family.
AB  - BACKGROUND: Grapevine is subjected to numerous pests and diseases resulting in
      the use of phytochemicals in large quantities. The will to decrease the use of
      phytochemicals leads to attempts to find alternative strategies, implying
      knowledge of defence mechanisms. Numerous studies have led to the identification
      of signalling pathways and regulatory elements involved in defence in various
      plant species. Nonexpressor of Pathogenesis Related 1 (NPR1) is an important
      regulatory component of systemic acquired resistance (SAR) in Arabidopsis
      thaliana. RESULTS: Two putative homologs of NPR1 gene were found in the two
      sequenced grapevine genomes available in the Genoscope database for line 40024
      and in the IASMA database for Pinot noir ENTAV 115. We named these two NPR1 genes
      of Vitis vinifera : VvNPR1.1 and VvNPR1.2. A PCR-based strategy with primers
      designed on exons was used to successfully amplify NPR1 gene fragments from
      different Vitaceae accessions. Sequence analyses show that NPR1.1 and NPR1.2 are
      highly conserved among the different accessions not only V. vinifera cultivars
      but also other species. We report nucleotide polymorphisms in NPR1.1 and NPR1.2
      from fifteen accessions belonging to the Vitaceae family. The ratio of
      nonsynonymous to synonymous nucleotide substitutions determines the evolutionary
      pressures acting on the Vitaceae NPR1 genes. These genes appear to be
      experiencing purifying selection. In some of the species we have analysed one of
      the two alleles of NPR1.1 contains a premature stop codon. The deduced amino acid
      sequences share structural features with known NPR1-like proteins: ankyrin
      repeats, BTB/POZ domains, nuclear localization signature and cysteines.
      Phylogenetic analyses of deduced amino acid sequences show that VvNPR1.1 belongs
      to a first group of NPR1 proteins known as positive regulators of SAR and
      VvNPR1.2 belongs to a second group of NPR1 proteins whose principal members are
      AtNPR3 and AtNPR4 defined as negative regulators of SAR. CONCLUSION: Our study
      shows that NPR1.1 and NPR1.2 are highly conserved among different accessions in
      the Vitaceae family. VvNPR1.1 and VvNPR1.2 are phylogenetically closer to the
      group of positive or negative SAR regulators respectively.

PMID- 20137082
TI  - Pathological complete response induced by first-line chemotherapy with single
      agent docetaxel in a patient with advanced non small cell lung cancer.
AB  - BACKGROUND: Defining the optimal treatment for patients with inoperable non small
      cell lung cancer (NSCLC), presenting with metastatic mediastinal lymph nodes, is
      challenging. Nevertheless, preoperative chemotherapy or radiotherapy might offer
      a chance for these patients for radical surgical resection and, possibly,
      complete recovery. CASE PRESENTATION: A 62-year old man with IIIA-N2 inoperable
      NSCLC was treated with first-line single agent docetaxel. A platinum-based
      treatment, though considered more active, was ruled out because of renal
      impairment. The patient tolerated the treatment very well and, although his
      initial response was not impressive, after 14 cycles he obtained a complete
      clinical response, which was confirmed pathologically after he underwent surgical
      lobectomy. CONCLUSION: In non-operable NSCLC patients not eligible for a platinum
      based treatment, single-agent docetaxel can provide complete pathologic
      responses. Failure to obtain a response after the first few cycles should not
      automatically discourage to continue treatment.

PMID- 20137083
TI  - Bayesian mapping of pulmonary tuberculosis in Antananarivo, Madagascar.
AB  - BACKGROUND: Tuberculosis (TB), an infectious disease caused by the Mycobacterium
      tuberculosis is endemic in Madagascar. The capital, Antananarivo is the most
      seriously affected area. TB had a non-random spatial distribution in this
      setting, with clustering in the poorer areas. The aim of this study was to
      explore this pattern further by a Bayesian approach, and to measure the
      associations between the spatial variation of TB risk and national control
      program indicators for all neighbourhoods. METHODS: Combination of a Bayesian
      approach and a generalized linear mixed model (GLMM) was developed to produce
      smooth risk maps of TB and to model relationships between TB new cases and
      national TB control program indicators. The TB new cases were collected from
      records of the 16 Tuberculosis Diagnostic and Treatment Centres (DTC) of the city
      from 2004 to 2006. And five TB indicators were considered in the analysis: number
      of cases undergoing retreatment, number of patients with treatment failure and
      those suffering relapse after the completion of treatment, number of households
      with more than one case, number of patients lost to follow-up, and proximity to a
      DTC. RESULTS: In Antananarivo, 43.23% of the neighbourhoods had a standardized
      incidence ratio (SIR) above 1, of which 19.28% with a TB risk significantly
      higher than the average. Identified high TB risk areas were clustered and the
      distribution of TB was found to be associated mainly with the number of patients
      lost to follow-up (SIR: 1.10, CI 95%: 1.02-1.19) and the number of households
      with more than one case (SIR: 1.13, CI 95%: 1.03-1.24). CONCLUSION: The spatial
      pattern of TB in Antananarivo and the contribution of national control program
      indicators to this pattern highlight the importance of the data recorded in the
      TB registry and the use of spatial approaches for assessing the epidemiological
      situation for TB. Including these variables into the model increases the
      reproducibility, as these data are already available for individual DTCs. These
      findings may also be useful for guiding decisions related to disease control
      strategies.

PMID- 20137084
TI  - Coupling of receptor interference and a host-dependent post-binding entry
      deficiency in a gammaretroviral envelope protein.
AB  - BACKGROUND: SL3-2 is a unique polytropic murine gammaretroviral isolate that is
      only able to infect murine cells. We have previously shown that two mutations
      R212G and T213I located on the surface of the receptor binding domain in a region
      designated the VR3 loop can alter the species tropism of this envelope protein.
      This location suggests that the VR3 loop composition has an influence on receptor
      interaction and thereby affects binding as well as superinfection resistance. In
      order to investigate this further, we have studied the binding and interference
      patterns of the SL3-2 envelope and its mutants. RESULTS: We find unexpectedly
      that wild type SL3-2 envelope binds equally well to both permissive and non
      permissive cells, indicating a post binding defect when interacting with the
      human Xpr1. Using replication competent viruses containing envelopes from SL3-2
      or its mutants we find that the same amino acid mutations can dramatically alter
      the interference profile of this polytropic ENV, suggesting that the same amino
      acid changes that cause the post binding defect also influence interaction with
      the receptor. CONCLUSIONS: The envelope protein of SL3-2 MLV shows an entry
      defect on non-murine cells. This is coupled to a dramatically reduced ability to
      interfere with entry of other polytropic viruses. Two point mutations in the VR3
      loop of the receptor binding domain of this envelope result both in a much
      increased interference ability and in removing the post-binding defect on non
      murine cells, suggesting that both of these phenotypes are a consequence of
      insufficient interaction between the envelope and the receptor.

PMID- 20137085
TI  - Early recurrence of thoracolumbar intervertebral disc extrusion after surgical
      decompression: a report of three cases.
AB  - Thoracolumbar disc extrusions were diagnosed in three chondrodystrophic dogs with
      paraparesis of up to three days duration. All cases were managed by
      hemilaminectomy and removal of extruded disc material. In one dog, fenestration
      of the herniated disc space was also performed. Initially neurological function
      improved or was unchanged, but from two to ten days postoperatively clinical
      signs of deterioration became apparent. In all the dogs, recurrence of disc
      extrusion at the same location as the initial extrusion was diagnosed by computer
      tomography and at a second surgery abundant disc material was found at the
      hemilaminectomy site between the dura and an implanted graft of autogenous fat.

PMID- 20137086
TI  - Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum
      of diabetic rats.
AB  - Glucose homeostasis in humans is an important factor for the functioning of
      nervous system. Hypoglycemia and hyperglycemia is found to be associated with
      central and peripheral nerve system dysfunction. Changes in acetylcholine
      receptors have been implicated in the pathophysiology of many major diseases of
      the central nervous system (CNS). In the present study we showed the effects of
      insulin induced hypoglycemia and streptozotocin induced diabetes on the
      cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results
      showed enhanced binding parameters and gene expression of Muscarinic M1, M3
      receptor subtypes in cerebellum of diabetic (D) and hypoglycemic group (D + IIH
      and C + IIH). alpha7nAchR gene expression showed a significant upregulation in
      diabetic group and showed further upregulated expression in both D + IIH and C +
      IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic
      group. ChAT showed downregulation and GLUT3 expression showed a significant
      upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in
      the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a
      functional disturbance in the neuronal glucose transporter GLUT3 in the
      cerebellum during insulin induced hypoglycemia in diabetic rats. Altered
      expression of muscarinic M1, M3 and alpha7nAchR and increased muscle AchE
      activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and
      motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression
      is suggested to cause impaired acetycholine metabolism in the cerebellum.
      Cerebellar dysfunction is associated with seizure generation, motor deficits and
      memory impairment. The results shows that cerebellar cholinergic
      neurotransmission is impaired during hyperglycemia and hypoglycemia and the
      hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission
      which is suggested to be a cause of cerebellar dysfunction associated with
      hypoglycemia.

PMID- 20137087
TI  - Comparative transcriptome analysis coupled to X-ray CT reveals sucrose supply and
      growth velocity as major determinants of potato tuber starch biosynthesis.
AB  - BACKGROUND: Even though the process of potato tuber starch biosynthesis is well
      understood, mechanisms regulating biosynthesis are still unclear. Transcriptome
      analysis provides valuable information as to how genes are regulated. Therefore,
      this work aimed at investigating transcriptional regulation of starch
      biosynthetic genes in leaves and tubers of potato plants under various
      conditions. More specifically we looked at gene expression diurnally in leaves
      and tubers, during tuber induction and in tubers growing at different velocities.
      To determine velocity of potato tuber growth a new method based on X-ray Computed
      Tomography (X-ray CT) was established. RESULTS: Comparative transcriptome
      analysis between leaves and tubers revealed striking similarities with the same
      genes being differentially expressed in both tissues. In tubers, oscillation of
      granule bound starch synthase (GBSS) expression) was observed which could be
      linked to sucrose supply from source leaves. X-ray CT was used to determine time
      dependent changes in tuber volume and the growth velocity was calculated.
      Although there is not a linear correlation between growth velocity and expression
      of starch biosynthetic genes, there are significant differences between growing
      and non-growing tubers. Co-expression analysis was used to identify transcription
      factors positively correlating with starch biosynthetic genes possibly regulating
      starch biosynthesis. CONCLUSION: Most starch biosynthetic enzymes are encoded by
      gene families. Co-expression analysis revealed that the same members of these
      gene families are co-regulated in leaves and tubers. This suggests that
      regulation of transitory and storage starch biosynthesis in leaves and tubers,
      respectively, is surprisingly similar. X-ray CT can be used to monitor growth and
      development of belowground organs and allows to link tuber growth to changes in
      gene expression. Comparative transcriptome analysis provides a useful tool to
      identify transcription factors possibly involved in the regulation of starch
      biosynthesis.

PMID- 20137088
TI  - Development and validation of the Treatment Related Impact Measure of Weight
      (TRIM-Weight).
AB  - BACKGROUND: The use of prescription anti-obesity medication (AOM) is becoming
      increasingly common as treatment options grow and become more accessible.
      However, AOM may not be without a wide range of potentially negative impacts on
      patient functioning and well being. The Treatment Related Impact Measure (TRIM
      Weight) is an obesity treatment-specific patient reported outcomes (PRO) measure
      designed to assess the key impacts of prescription anti-obesity medication. This
      paper will present the validation findings for the TRIM-Weight. METHODS: The
      online validation battery survey was administered in four countries (the U.S.,
      U.K., Australia, and Canada). Eligible subjects were over age eighteen, currently
      taking a prescription AOM and were currently or had been obese during their life.
      Validation analyses were conducted according to an a priori statistical analysis
      plan. Item level psychometric and conceptual criteria were used to refine and
      reduce the preliminary item pool and factor analysis to identify structural
      domains was performed. Reliability and validity testing was then performed and
      the minimally importance difference (MID) explored. RESULTS: Two hundred and
      eight subjects completed the survey. Twenty-one of the 43 items were dropped and
      a five-factor structure was achieved: Daily Life, Weight Management, Treatment
      Burden, Experience of Side Effects, and Psychological Health. A-priori criteria
      for internal consistency and test-retest coefficients for the total score and all
      five subscales were met. All pre-specified hypotheses for convergent and known
      group validity were also met with the exception of the domain of Daily Life
      (proven in an ad hoc analysis) as well as the 1/2 standard deviation threshold
      for the MID. CONCLUSION: The development and validation of the TRIM-Weight has
      been conducted according to well-defined principles for the creation of a PRO
      measure. Based on the evidence to date, the TRIM-Weight can be considered a
      brief, conceptually sound, valid and reliable PRO measure.

PMID- 20137089
TI  - Onconase responsive genes in human mesothelioma cells: implications for an RNA
      damaging therapeutic agent.
AB  - BACKGROUND: Onconase represents a new class of RNA-damaging drugs.
      Mechanistically, Onconase is thought to internalize, where it degrades
      intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses
      protein synthesis. However, there may be additional or alternative mechanism(s)
      of action. METHODS: In this study, microarray analysis was used to compare gene
      expression profiles in untreated human malignant mesothelioma (MM) cell lines and
      cells exposed to 5 microg/ml Onconase for 24 h. A total of 155 genes were found
      to be regulated by Onconase that were common to both epithelial and biphasic MM
      cell lines. Some of these genes are known to significantly affect apoptosis (IL
      24, TNFAIP3), transcription (ATF3, DDIT3, MAFF, HDAC9, SNAPC1) or inflammation
      and the immune response (IL-6, COX-2). RT-PCR analysis of selected up- or down
      regulated genes treated with varying doses and times of Onconase generally
      confirmed the expression array findings in four MM cell lines. RESULTS: Onconase
      treatment consistently resulted in up-regulation of IL-24, previously shown to
      have tumor suppressive activity, as well as ATF3 and IL-6. Induction of ATF3 and
      the pro-apoptotic factor IL-24 by Onconase was highest in the two most responsive
      MM cell lines, as defined by DNA fragmentation analysis. In addition to
      apoptosis, gene ontology analysis indicated that pathways impacted by Onconase
      include MAPK signaling, cytokine-cytokine-receptor interactions, and Jak-STAT
      signaling. CONCLUSIONS: These results provide a broad picture of gene activity
      after treatment with a drug that targets small non-coding RNAs and contribute to
      our overall understanding of MM cell response to Onconase as a therapeutic
      strategy. The findings provide insights regarding mechanisms that may contribute
      to the efficacy of this novel drug in clinical trials of MM patients who have
      failed first line chemotherapy or radiation treatment.

PMID- 20137090
TI  - Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol.
AB  - BACKGROUND: There is increasing evidence that tight blood glucose (BG) control
      improves outcomes in critically ill adults. Children show similar hyperglycaemic
      responses to surgery or critical illness. However it is not known whether tight
      control will benefit children given maturational differences and different
      disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two
      parallel groups to assess whether, for children undergoing intensive care in the
      UK aged <or= 16 years who are ventilated, have an arterial line in-situ and are
      receiving vasoactive support following injury, major surgery or in association
      with critical illness in whom it is anticipated such treatment will be required
      to continue for at least 12 hours, tight control will increase the numbers of
      days alive and free of mechanical ventilation at 30 days, and lead to improvement
      in a range of complications associated with intensive care treatment and be cost
      effective. Children in the tight control group will receive insulin by
      intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children
      in the control group will be treated according to a standard current approach to
      BG management. Children will be followed up to determine vital status and
      healthcare resources usage between discharge and 12 months post-randomisation.
      Information regarding overall health status, global neurological outcome,
      attention and behavioural status will be sought from a subgroup with traumatic
      brain injury (TBI). A difference of 2 days in the number of ventilator-free days
      within the first 30 days post-randomisation is considered clinically important.
      Conservatively assuming a standard deviation of a week across both trial arms, a
      type I error of 1% (2-sided test), and allowing for non-compliance, a total
      sample size of 1000 patients would have 90% power to detect this difference. To
      detect effect differences between cardiac and non-cardiac patients, a target
      sample size of 1500 is required. An economic evaluation will assess whether the
      costs of achieving tight BG control are justified by subsequent reductions in
      hospitalisation costs. DISCUSSION: The relevance of tight glycaemic control in
      this population needs to be assessed formally before being accepted into standard
      practice.

PMID- 20137091
TI  - Evaluation of a community pharmacy-based intervention for improving patient
      adherence to antihypertensives: a randomised controlled trial.
AB  - BACKGROUND: The majority of patients using antihypertensive medications fail to
      achieve their recommended target blood pressure. Poor daily adherence with
      medication regimens and a lack of persistence with medication use are two of the
      major reasons for failure to reach target blood pressure. There is no single
      intervention to improve adherence with antihypertensives that is consistently
      effective. Community pharmacists are in an ideal position to promote adherence to
      chronic medications. This study aims to test a specific intervention package that
      could be integrated into the community pharmacy workflow to enable pharmacists to
      improve patient adherence and/or persistence with antihypertensive medications-
      Hypertension Adherence Program in Pharmacy (HAPPY). METHODS/DESIGN: The HAPPY
      trial is a multi-centre prospective randomised controlled trial. Fifty-six
      pharmacies have been recruited from three Australian states. To identify
      potential patients, a software application (MedeMine CVD) extracted data from a
      community pharmacy dispensing software system (FRED Dispense). The pharmacies
      have been randomised to either 'Pharmacist Care Group' (PCG) or 'Usual Care
      Group' (UCG). To check for 'Hawthorne effect' in the UCG, a third group of
      patients 'Hidden Control Group' (HCG) will be identified in the UCG pharmacies,
      which will be made known to the pharmacists at the end of six months. Each study
      group requires 182 patients. Data will be collected at baseline, three and six
      months in the PCG and at baseline and six months in the UCG. Changes in patient
      adherence and persistence at the end of six months will be measured using the
      self-reported Morisky score, the Tool for Adherence Behaviour Screening and
      medication refill data. DISCUSSION: To our knowledge, this is the first research
      testing a comprehensive package of evidence-based interventions that could be
      integrated into the community pharmacy workflow to enable pharmacists to improve
      patient adherence and/or persistence with antihypertensive medications. The
      unique features of the HAPPY trial include the use of MedeMine CVD to identify
      patients who could potentially benefit from the service, control for the
      'Hawthorne effect' in the UCG and the offer of the intervention package at the
      end of six months to patients in the UCG, a strategy that is expected to improve
      retention. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry
      ACTRN12609000705280.

PMID- 20137092
TI  - Regulations of the key mediators in inflammation and atherosclerosis by aspirin
      in human macrophages.
AB  - Although its role to prevent secondary cardiovascular complications has been well
      established, how acetyl salicylic acid (ASA, aspirin) regulates certain key
      molecules in the atherogenesis is still not known. Considering the role of matrix
      metalloproteinase-9 (MMP-9) to destabilize the atherosclerotic plaques, the roles
      of the scavenger receptor class BI (SR-BI) and ATP-binding cassette transporter
      A1 (ABCA1) to promote cholesterol efflux in the foam cells at the plaques, and
      the role of NF-kappaB in the overall inflammation related to the atherosclerosis,
      we addressed whether these molecules are all related to a common mechanism that
      may be regulated by acetyl salicylic acid. We investigated the effect of ASA to
      regulate the expressions and activities of these molecules in THP-1 macrophages.
      Our results showed that ASA inhibited MMP-9 mRNA expression, and caused the
      decrease in the MMP-9 activities from the cell culture supernatants. In addition,
      it inhibited the nuclear translocation of NF-kappaB p65 subunit, thus the
      activity of this inflammatory molecule. On the contrary, acetyl salicylic acid
      induced the expressions of ABCA1 and SR-BI, two molecules known to reduce the
      progression of atherosclerosis, at both mRNA and protein levels. It also
      stimulated the cholesterol efflux out of macrophages. These data suggest that
      acetyl salicylic acid may alleviate symptoms of atherosclerosis by two potential
      mechanisms: maintaining the plaque stability via inhibiting activities of
      inflammatory molecules MMP-9 and NF-kappaB, and increasing the cholesterol efflux
      through inducing expressions of ABCA1 and SR-BI.

PMID- 20137093
TI  - FDG-PET/CT imaging for staging and target volume delineation in conformal
      radiotherapy of anal carcinoma.
AB  - BACKGROUND: FDG-PET/CT imaging has an emerging role in staging and treatment
      planning of various tumor locations and a number of literature studies show that
      also the carcinoma of the anal canal may benefit from this diagnostic approach.
      We analyzed the potential impact of FDG-PET/CT in stage definition and target
      volume delineation of patients affected by carcinoma of the anal canal and
      candidates for curative radiotherapy. METHODS: Twenty seven patients with biopsy
      proven anal carcinoma were enrolled. Pathology was squamous cell carcinoma in 20
      cases, cloacogenic carcinoma in 3, adenocarcinoma in 2, and basal cell carcinoma
      in 2. Simulation was performed by PET/CT imaging with patient in treatment
      position. Gross Tumor Volume (GTV) and Clinical Target Volume (CTV) were drawn on
      CT and on PET/CT fused images. PET-GTV and PET-CTV were respectively compared to
      CT-GTV and CT-CTV by Wilcoxon rank test for paired data. RESULTS: PET/CT fused
      images led to change the stage in 5/27 cases (18.5%): 3 cases from N0 to N2 and 2
      from M0 to M1 leading to change the treatment intent from curative to palliative
      in a case.Based on PET/CT imaging, GTV and CTV contours changed in 15/27 (55.6%)
      and in 10/27 cases (37.0%) respectively. PET-GTV and PET-CTV resulted
      significantly smaller than CT-GTV (p = 1.2 x 10(-4)) and CT-CTV (p = 2.9 x 10(
      4)). PET/CT-GTV and PET/CT-CTV, that were used for clinical purposes, were
      significantly greater than CT-GTV (p = 6 x 10(-5)) and CT-CTV (p = 6 x 10(-5)).
      CONCLUSIONS: FDG-PET/CT has a potential relevant impact in staging and target
      volume delineation of the carcinoma of the anal canal. Clinical stage variation
      occurred in 18.5% of cases with change of treatment intent in 3.7%. The GTV and
      the CTV changed in shape and in size based on PET/CT imaging.

PMID- 20137094
TI  - Total knee arthroplasties performed with a mini-incision or a standard incision.
      Similar results at six months follow-up.
AB  - BACKGROUND: Minimal invasion surgery (MIS) is a recent technique recommended for
      Total knee arthroplasty (TKA) but demands an effort of the surgeons and the
      learning curve may be long. METHODS: Twenty six MIS-TKA were matched to 36
      standard TKA with respect to age, sex, body mass index or preoperative score. All
      patients suffered from knee osteoarthritis, which had not improved with medical
      treatment and which presented a less than 10 degrees deformity in the coronal and
      sagittal radiographic projections. At six months after the surgery a specific
      questionnaire was completed as well as the KSS (Knee Society rating scale), the
      generic short-form health questionnaire (SF-12) and a visual analogue scale
      (VAS). RESULTS: The MIS technique required more time of surgery (p < 0.001),
      hospital stay was noticeably shorter (p < 0.05) and drainage volume collected
      after surgery was significantly higher in the standard technique. We observe a
      higher frequency in small sizes implants for MIS surgery but no statistically
      significant differences were found between both groups regarding the radiological
      alignment of the implant. At six months no differences were found between the
      groups in range of motion, KSS scores, the physical or mental subscale SF-12,
      patient's pain perception, satisfaction or subjective improvement. CONCLUSIONS:
      Minimal invasion surgery in total knee arthroplasty showed no improvement over a
      standard approach.

PMID- 20137095
TI  - Transcription factors Elk-1 and SRF are engaged in IL1-dependent regulation of
      ZC3H12A expression.
AB  - BACKGROUND: MCPIP is a novel CCCH zinc finger protein described as an RNase
      engaged in the regulation of immune responses. The regulation of expression of
      the gene coding for MCPIP - ZC3H12A is poorly explored. RESULTS: Here we report
      that the proinflammatory cytokine IL-1beta rapidly induces the synthesis of MCPIP
      in primary monocyte-derived macrophages and HepG2 cells. This up-regulation takes
      place through the MAP kinase pathway and following activation of the
      transcription factor Elk-1. Using a ZC3H12A reporter construct we have shown that
      a ZC3H12A promoter region, stretching from -76 to +60, mediates activation by IL
      1beta. This region contains binding sites for Elk-1 and its partner SRF.
      Chromatin immunoprecipitation analysis confirms in vivo binding of both
      transcription factors to this region of the ZC3H12A promoter. CONCLUSIONS: We
      conclude that the transcription factor Elk-1 plays an important role in the
      activation of ZC3H12A expression in response to IL-1beta stimulation.

PMID- 20137096
TI  - Survival after prolonged resuscitation with 99 defibrillations due to Torsade De
      Pointes cardiac electrical storm: a case report.
AB  - A 48-year-old previously healthy woman suffered witnessed cardiac arrest in
      hospital. She achieved return of spontaneous circulation and was transferred to
      the intensive care unit. During the following 3 hours, she suffered a cardiac
      electrical storm with 98 episodes of Torsade de Pointes ventricular tachycardia
      rapidly degenerating to ventricular fibrillation. She was converted with a total
      of 99 defibrillations. There was no response to the use of any recommended anti
      arrhythmic drugs. However, the use of bretylium surprisingly stabilized her heart
      rhythm and facilitated placing of a temporary pacemaker. Overdrive pacing
      prevented further arrhythmias and was life saving. A number of beneficial factors
      may have contributed to the good neurological outcome. Further investigations
      gave no explanation for her cardiac electrical storm.

PMID- 20137097
TI  - The prevalence of atypical scrapie in sheep from positive flocks is not higher
      than in the general sheep population in 11 European countries.
AB  - BACKGROUND: During the last decade, active surveillance for transmissible
      spongiform encephalopathies in small ruminants has been intensive in Europe. In
      many countries this has led to the detection of cases of atypical scrapie which,
      unlike classical scrapie, might not be contagious. EU legislation requires, that
      following detection of a scrapie case, control measures including further testing
      take place in affected flocks, including the culling of genotype susceptible to
      classical scrapie. This might result in the detection of additional cases. The
      aim of this study was to investigate the occurrence of additional cases in flocks
      affected by atypical scrapie using surveillance data collected in Europe in order
      to ascertain whether atypical scrapie, is contagious. RESULTS: Questionnaires
      were used to collect, at national level, the results of active surveillance and
      testing associated with flock outbreaks in 12 European countries. The mean
      prevalence of atypical scrapie was 5.5 (5.0-6.0) cases per ten thousand in
      abattoir surveillance and 8.1 (7.3-9.0) cases per ten thousand in fallen stock.
      By using meta-analysis, on 11 out of the 12 countries, we found that the
      probability of detecting additional cases of atypical scrapie in positive flocks
      was similar to the probability observed in animals slaughtered for human
      consumption (odds ratio, OR = 1.07, CI95%: 0.70-1.63) or among fallen stock (OR =
      0.78, CI95%: 0.51-1.2). In contrast, when comparing the two scrapie types, the
      probability of detecting additional cases in classical scrapie positive flocks
      was significantly higher than the probability of detecting additional cases in
      atypical scrapie positive flocks (OR = 32.4, CI95%: 20.7-50.7). CONCLUSIONS:
      These results suggest that atypical scrapie is not contagious or has a very low
      transmissibility under natural conditions compared with classical scrapie.
      Furthermore this study stressed the importance of standardised data collection to
      make good use of the analyses undertaken by European countries in their efforts
      to control atypical and classical scrapie.

PMID- 20137098
TI  - Ethnomedical survey of plants used by the Orang Asli in Kampung Bawong, Perak,
      West Malaysia.
AB  - BACKGROUND: A qualitative ethnomedical survey was carried out among a local Orang
      Asli tribe to gather information on the use of medicinal plants in the region of
      Kampung Bawong, Perak of West Malaysia in order to evaluate the potential
      medicinal uses of local plants used in curing different diseases and illnesses.
      METHODS: Sixteen informants ranging in age from 35 to 65 years were interviewed.
      A total of 62 species of plants used by Orang Asli are described in this study
      based on field surveys and direct face to face communication. These plants
      belonged to 36 families and are used to treat a wide range of discomforts and
      diseases. RESULTS: The results of this study showed that majority of the Orang
      Asli, of Kampung Bawong are still dependent on local plants as their primary
      source of medication. As the first ethnomedical study in this area, publishing
      this work is expected to open up more studies to identify and assess the
      pharmacological and toxicological action of the plants from this region.
      CONCLUSIONS: Preservation and recording of ethnobotanical and ethnomedical uses
      of traditional medicinal plants is an indispensable obligation for sustaining the
      medicinal and cultural resource of mankind. Extensive research on such
      traditional plants is of prime importance to scientifically validate their
      ethnomedical claims.

PMID- 20137099
TI  - Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung
      injury/fibrosis.
AB  - BACKGROUND: No effective treatment for acute lung injury and fibrosis currently
      exists. Aim of this study was to investigate the time-dependent effect of bone
      marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute
      lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine
      production. METHODS: BMDMSCs were transferred 4 days after BLM inhalation.
      Wet/dry ratio, bronchoalveolar lavage cell profiles, histologic changes and
      deposition of collagen were analyzed. RESULTS: Nitrite, nitrate and cytokines
      were measured weekly through day 28. At day 7, the wet/dry ratio, neutrophilic
      inflammation, and amount of collagen were elevated in BLM-treated rats compared
      to sham rats (p = 0.05-0.002). Levels nitrite, nitrate, IL-1beta, IL-6, TNF
      alpha, TGF-beta and VEGF were also higher at day 7 (p < 0.05). Degree of
      lymphocyte and macrophage infiltration increased steadily over time. BMDMSC
      transfer significantly reduced the BLM-induced increase in wet/dry ratio, degree
      of neutrophilic infiltration, collagen deposition, and levels of the cytokines,
      nitrite, and nitrate to those in sham-treated rats (p < 0.05). Fluorescence in
      situ hybridization localized the engrafted cells to areas of lung injury.
      CONCLUSION: Systemic transfer of BMDMSCs effectively reduced the BLM-induced lung
      injury and fibrosis through the down-regulation of nitric oxide metabolites, and
      proinflammatory and angiogenic cytokines.

PMID- 20137100
TI  - Complete genome sequence of human astrovirus genotype 6.
AB  - BACKGROUND: Human astroviruses (HAstVs) are one of the important causes of acute
      gastroenteritis in children. Currently, eight HAstV genotypes have been
      identified and all but two (HAstV-6 and HAstV-7) have been fully sequenced. We
      here sequenced and analyzed the complete genome of a HAstV-6 strain (192-BJ07),
      which was identified in Beijing, China. RESULTS: The genome of 192-BJ07 consists
      of 6745 nucleotides. The 192-BJ07 strain displays a 77.2-78.0% nucleotide
      sequence identity with other HAstV genotypes and exhibits amino acid sequence
      identities of 86.5-87.4%, 94.2-95.1%, and 65.5-74.8% in the ORF1a, ORF1b, and
      ORF2 regions, respectively. Homological analysis of ORF2 shows that 192-BJ07 is
      96.3% identical to the documented HAstV-6 strain. Further, phylogenetic analysis
      indicates that different genomic regions are likely undergoing different
      evolutionary and selective pressures. No recombination event was observed in
      HAstV-6 in this study. CONCLUSION: The completely sequenced and characterized
      genome of HAstV-6 (192-BJ07) provides further insight into the genetics of
      astroviruses and aids in the surveillance and control of HAstV gastroenteritis.

PMID- 20137101
TI  - Genome-wide investigation and functional characterization of the beta-ketoadipate
      pathway in the nitrogen-fixing and root-associated bacterium Pseudomonas stutzeri
      A1501.
AB  - BACKGROUND: Soil microorganisms are mainly responsible for the complete
      mineralization of aromatic compounds that usually originate from plant products
      or environmental pollutants. In many cases, structurally diverse aromatic
      compounds can be converted to a small number of structurally simpler
      intermediates, which are metabolized to tricarboxylic acid intermediates via the
      beta-ketoadipate pathway. This strategy provides great metabolic flexibility and
      contributes to increased adaptation of bacteria to their environment. However,
      little is known about the evolution and regulation of the beta-ketoadipate
      pathway in root-associated diazotrophs. RESULTS: In this report, we performed a
      genome-wide analysis of the benzoate and 4-hydroxybenzoate catabolic pathways of
      Pseudomonas stutzeri A1501, with a focus on the functional characterization of
      the beta-ketoadipate pathway. The P. stutzeri A1501 genome contains sets of
      catabolic genes involved in the peripheral pathways for catabolism of benzoate
      (ben) and 4-hydroxybenzoate (pob), and in the catechol (cat) and protocatechuate
      (pca) branches of the beta-ketoadipate pathway. A particular feature of the
      catabolic gene organization in A1501 is the absence of the catR and pcaK genes
      encoding a LysR family regulator and 4-hydroxybenzoate permease, respectively.
      Furthermore, the BenR protein functions as a transcriptional activator of the ben
      operon, while transcription from the catBC promoter can be activated in response
      to benzoate. Benzoate degradation is subject to carbon catabolite repression
      induced by glucose and acetate in A1501. The HPLC analysis of intracellular
      metabolites indicated that low concentrations of 4-hydroxybenzoate significantly
      enhance the ability of A1501 to degrade benzoate. CONCLUSIONS: The expression of
      genes encoding proteins involved in the beta-ketoadipate pathway is tightly
      modulated by both pathway-specific and catabolite repression controls in A1501.
      This strain provides an ideal model system for further study of the evolution and
      regulation of aromatic catabolic pathways.

PMID- 20137102
TI  - Climate change: time to redefine our profession.

PMID- 20137103
TI  - Climate change and the public health nutrition agenda.

PMID- 20137104
TI  - Neoriojatrema mokokchungensis n. g., n. sp. (Monogenea: Polystomatidae:
      Polystomatinae) from the urinary bladder of a megophryid frog, Xenophrys
      glandulosa, in Nagaland, north-eastern India.
AB  - A new monogenean fluke, collected from the urinary bladder of a megophryid frog,
      Xenophrys glandulosa Fei, Ye & Huang, 1991 from Mokokchung and Tuensang districts
      of Nagaland, north-eastern India is described. Of the six genera under the
      subfamily Polystomatinae (Polystomatidae) known so far, the present form comes
      closer to Eupolystoma Kaw, 1950; Pseudopolystoma Yamaguti, 1963 and Riojatrema
      Lamothe-Argumedo, 1964, in all of which the opisthaptor lacks large hooks.
      However, a combination of characters, namely, shape of the body, rounded or
      bulbous pharynx, intestinal caeca not joining posteriorly in the opisthaptoral
      region, ovary located in the anterior third of the body and presence of vaginal
      apertures, sets the present form apart from all these genera, and also from the
      known species of Riojatrema. These differences warrant the establishment of a new
      species and a new genus to accommodate the present form. The validity of this new
      monogenean, named as Neoriojatrema mokokchungensis after the type locality of the
      fluke, is discussed.

PMID- 20137105
TI  - Parasitic castration of Buccinanops cochlidium (Gastropoda: Nassariidae) caused
      by a lepocreadiid digenean in San Jose Gulf, Argentina.
AB  - Parasitic castration of Buccinanops cochlidium from San Jose Gulf, Argentina,
      caused by a lepocreadiid digenean, is reported for the first time. Rediae and
      ophtalmotrichocercous cercariae probably belonging to Opechona sp. were
      identified in the gonad and digestive gland. Opechona sp. has been reported
      previously parasitizing B. monilifer from a northern locality in the Argentine
      Sea. Overall prevalence of infection was 15.5%; it varied seasonally, rising
      during the warm months after the host oviposition period. Cercariae were expelled
      at the same time as the hatching of snail embryos (during the higher water
      temperature period). Rediae affected male and female snails equally, but
      prevalence increases along with host size. The parasite causes the complete
      castration of the host. Parasitized adult snails showed a reduction of penis size
      in comparison with healthy males. It remains to be confirmed whether the peak of
      cercariae emission coincides with the presence of jellyfishes and scombrid or
      other fishes in the area, which could act as second intermediate and definitive
      hosts, respectively.

PMID- 20137106
TI  - Sounds can affect visual perception mediated primarily by the parvocellular
      pathway.
AB  - We investigated the effect of auditory-visual sensory integration on visual tasks
      that were predominantly dependent on parvocellular processing. These tasks were
      (i) detecting metacontrast-masked targets and (ii) discriminating orientation
      differences between high spatial frequency Gabor patch stimuli. Sounds that
      contained no information relevant to either task were presented before,
      synchronized with, or after the visual targets, and the results were compared to
      conditions with no sound. Both tasks used a two-alternative forced choice
      technique. For detecting metacontrast-masked targets, one interval contained the
      visual target and both (or neither) intervals contained a sound. Sound-target
      synchrony within 50 ms lowered luminance thresholds for detecting the presence of
      a target compared to when no sound occurred or when sound onset preceded target
      onset. Threshold angles for discriminating the orientation of a Gabor patch
      consistently increased in the presence of a sound. These results are compatible
      with sound-induced activity in the parvocellular visual pathway increasing the
      visibility of flashed targets and hindering orientation discrimination.

PMID- 20137107
TI  - [Functional multi-polarization of white blood cells and its significance].
AB  - Immune and hemopoiesis are one of basic project of experimental hematology.
      Immune function is a essential activity of white blood cells. It was puzzled for
      the diversity and complexity of immune response. Polarized immune response of
      immune cells was discovered 30 years ago, which facilitates the study on
      differentiation of lymphocyte. Recently recognition on multifunctional polarized
      immune response of lymphocyte and monocyte/macrophage would promote to elucidate
      the regulatory network of immune cells, diversity and complexity of immune
      response as well as the study on hemopoiesis. In this paper the approach of
      multifunctional polarized immune response of lymphocyte, monocyte/macrophage and
      dendritic cells were reviewed, and their role, especially in cytokine storm and
      tumor pro-inflammation condition were discussed.

PMID- 20137108
TI  - [Role of N-cadherin in maintaining leukemic stem cell properties].
AB  - Self-renewal and drug resistance are key features of leukemic stem cells (LSC).
      To clarify the mechanism of maintaining LSC properties, the CD34(+) leukemic cell
      line KGla was used as study model to elucidate the role of N-cadherin in self
      renewal and drug resistance. N-cadherin positive and N-cadherin negative KG1a
      cell groups were sorted by flow cytometry. Self-renewal and the half maximal
      inhibitory concentration (IC(50)) of VP16 in two groups of KG1a cells were
      determined by colony formation assay and MTT assay. The results showed that cell
      colony formation ability of N-cadherin positive KG1a cells was significantly
      higher than that of N-cadherin negative KG1a cells. After treated with VP16, N
      cadherin positive KG1a cells showed higher chemoresistance than N-cadherin
      negative KG1a cells with IC(50) of 220 micro mol/L for N-cadherin positive cells
      and 151 micro mol/L for N-cadherin negative cells (p = 0.04). The results also
      showed that N-cadherin mediated adhesion participated in the chemoresistance of N
      cadherin positive cells. It is concluded that N-cadherin plays an important role
      in maintaining the self-renewal and drug resistance properties of LSC.

PMID- 20137109
TI  - [Expression of angiogenin-2 and VEGF in acute leukemia and its significance].
AB  - The aim of study was to investigate the expression of angiogenin-2 (Ang-2) and
      vascular endothelial growth factor (VEGF) expression in acute leukemia (AL) and
      its significance in the angiogenesis and progress of AL. Serum levels of Ang-2
      and VEGF in 24 de novo, 18 complete remitted (CR), 7 unremitted, 13 relapsed
      patients with AL were measured by enzyme-linked immunosorbent assay (ELISA), and
      compared with those of normal controls. The results showed that the serum levels
      of Ang-2 and VEGF in de novo, unremitted and relapsed patients were significantly
      higher than those in normal controls (p < 0.01). Compared with de novo group, the
      serum levels of Ang-2 and VEGF in CR patients decreased significantly, but
      showing no significant difference from those in normal controls (p > 0.05). In
      relapsed patients, the serum levels of Ang-2 and VEGF were obviously higher than
      those in unremitted and CR patients (p < 0.01). It is concluded that the
      expressions of Ang-2 and VEGF are closely related with occurrence and development
      of acute leukemia, the VEGF may regulate Ang-2 expression and promote
      angiogenesis and acute leukemia development. Preventing expressions of Ang-2 and
      VEGF may seem as targets for leukemia therapy in the future.

PMID- 20137110
TI  - [Expression and activity of glycosylphosphatidylinositol-specific phospholipase d
      mRNA in bone marrow mononuclear cells isolated from patient with acute myeloid
      leukemia and their significance].
AB  - This study was purposed to investigate the expression and significance of
      glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in bone marrow
      mononuclear cells (BMMNC) isolated from patients with acute myeloid leukemia
      (AML), GPI-PLD activity in BMMNC isolated from 78 patients with AML and 15 normal
      persons was measured by using GPI-anchored placental alkaline phosphatase (PLAP)
      as a substrate and Triton X-114 phase partitioning. The GPI-PLD mRNA expression
      was measured by semi-quantitive reverse transcription-polymerase chain reaction
      (RT-PCR). The results showed that the mRNA expression level and activity of GPI
      PLD in BMMNC from de novo AML patients were 1.86 +/- 0.32 and 46.96 +/- 7.15%
      respectively; the mRNA expression level and activity of GPI-PLD in BMMNC from
      completely remission and refractory or relapsed patients were 1.26 +/- 0.29,
      33.36 +/- 5.13%and 1.79 +/- 0.19, 44.31 +/- 7.22%, while those in BMMNC from
      normal controls were 1.27 +/- 0.23, 35.38 +/- 5.15% respectively. The mRNA
      expression level and activity of GPI-PLD in de novo and refractory or relapsed
      patients were obviously higher than those in normal controls with significant
      difference (p < 0.01), while the comparison between remitted patients and normal
      controls showed no statistical difference (p > 0.05). It is concluded that the
      expression level of GPI-PLD mRNA coincides with GPI-PLD activity. The mRNA
      expression and activity of GPI-PLD in de novo and refractory or relapsed patients
      are obviously higher than those in normal controls. It is worthy of further
      exploring whether GPI-PLD plays a certain role in process of leukemia
      pathogenesis.

PMID- 20137111
TI  - [Correlation of adult AML Npm1 mutations with prognosis and its relationship with
      gene mutation of FLT3 and CEBPA].
AB  - This study was aimed to investigate the correlation of 12th exon mutations in the
      npm1 gene with prognosis of adult AML patients and to explore the relationship of
      12th exon mutation with other gene mutations. The specimen of bone marrow and
      peripheral blood from AML patients, the informations of medical history,
      symptoms, related image examinations, blood routine examination, NAP, oxygen
      saturation level in artery blood and EPO level in serum were collected; the
      bcr/abl fusion gene was detected by routine examination of bone marrow + biopsy +
      chromosome mapping + FISH. The patients were typed according to WHO
      classification. The DNA in cells was extracted, the npm1 gene mutation was
      detected by allele specific PCR combined were the sequencing. The results
      indicated that the npm1 heterozygote gene mutation was found in 72 out of 150 AML
      patients with normal cytogenetics (48%, 72/150). 48% patients showed a frameshift
      mutation in the C-terminal region of the NPM1 protein. The AML patients with npm1
      gene mutation had specific clinical, phenotypic and genetic characteristics. The
      statistical analysis demonstrated the relationship between npm1 and flt3 ITDs.
      The patients with npm1 mutation showed a better response to induction therapy,
      furthermore, the overall survival (OS) rate of patients without flt3 ITD mutation
      was enhanced. The multivariate analysis demonstrated that the npm1 gene mutation
      and cebpa mutation positively correlated to the OS rate, and the correlation of
      flt3 mutation to OS rate showed negative. It is concluded that npm1 mutation is a
      favorable independent prognostic factor for adult AML patients with normal
      cytogenetics under conditions without FIT3 gene mutation.

PMID- 20137112
TI  - [Inhibition of leukemia cell proliferation by G-rich oligonucleotides].
AB  - G-rich oligonucleotides (GROs) belong to a novel class of phosphodiester
      oligonucleotides. They can form G-tetramer structure which contributes to cell
      cycle arrest and growth inhibitory effects by non-antisense pathway. This study
      was aimed to investigate the biological effects of GRO-26B on leukemia cell
      lines. Cell proliferation of different cell lines were detected by using MTT
      method and trypan blue incorporation assay. Alteration of cell cycle was analyzed
      by using flow cytometry. Apoptosis was detected by using Annexin V/PI kit.
      Western blot was used to detect the expression level of cyclins and CDKs.
      Morphological features of GRO-26B-treated cells was observed by light microscopy
      and transmission electron microscopy (TEM). The results showed that GRO-26B could
      inhibit the proliferation of AML cell lines, such as U937 and NB4 cells in a dose
      dependent manner. GRO-26B induced the cell cycle to be arrested at S phase in
      time-dependent manner, which was associated with the alteration of cyclin A,
      cyclin B, CDC2 and CDK2. The morphology of cells treated by GRO-26B also showed a
      distinct change as compared to the untreated cells. It is concluded that GRO-26B
      can inhibit AML cell proliferation, which is partially associated to cell cycle
      arrest at S phase. The S phase arrest is related to cyclins/CDKs. The regulation
      mechanism of cell cycle and proliferation is complicated. All of the above
      mentioned phenomena need to be studied in the future.

PMID- 20137113
TI  - [Regulation mechanism for rig-g gene expression induced by all-trans retinoic
      acid].
AB  - To investigate the molecular mechanisms of all-trans retinoic acid (ATRA)-induced
      rig-g gene expression and to better understand the signal transduction of ATRA
      during acute promyelocytic leukemia (APL) cell differentiation, the luciferase
      reporter assay, co-immunoprecipitation and chromatin immunoprecipitation were
      used to clarify the basic transcriptional factors, which directly initiated the
      expression of rig-g gene. The results showed that the expression of STAT2, IRF-9
      and IRF-1 could be upregulated by ATRA with different kinetics in NB4 cells. IRF
      9 was able to interact with STAT2 to form a complex, which could bind the rig-g
      gene promoter and trigger the rig-g expression. IRF-1 alone could also activate
      the reporter gene containing rig-g gene promoter, but C/EBPalpha could strongly
      inhibit this transcription activity of IRF-1. It is concluded that during ATRA
      induced APL cell differentiation, IRF-1 is first upregulated by ATRA, and then
      IRF-1 increases the protein levels of IRF-9 and STAT2 with the downregulation of
      C/EBPalpha. The complex of IRF-9 and STAT2 is the primary transcriptional factor
      for rig-g gene induction. This study will be helpful for better understanding the
      signal transduction networks of ATRA during the course of APL cell
      differentiation.

PMID- 20137114
TI  - [Correlation of deoxycytidine kinase gene expression with fludarabine resistance
      in patients with chronic lymphocytic leukemia].
AB  - The study was purposed to explore the relationship between the expression of
      deoxycytidine kinase (dCK) gene and fludarabine (Flud) resistance in patients
      with chronic lymphocytic leukemia (CLL). The real time quantitative polymerase
      chain reaction (RQ-PCR) technique was used to detect the mRNA expression of dCK
      gene in the bone marrow or peripheral blood mononuclear cells from 30 CLL
      patients, the difference of dCK expression levels between CLL patients sensitive
      to Flud and patients resistant to Flud was analyzed. The results showed that dCK
      expression level in the Flud-sensitive patients was much higher than that in the
      Flud-resistant ones (p = 0.001); dCK expression level had no relationship with
      sex, age, Binet stage, IgVH mutations, CD38, ZAP-70 or p53 gene mutation (p >
      0.05). It is concluded that low expression or deficiency of dCK in patients may
      contribute to resistance against Flud- and the prognostic significance of dCK
      expression remains to be further studied.

PMID- 20137115
TI  - [Inhibitory effect of siRNA targeting gene Aqp1 on K562 cells].
AB  - The objective of this study was to establish an RNAi approach that can
      specifically target aqp1 gene sequence in vitro, and to assess the inhibitory
      effect of this siRNA on K562 cells. The siRNA targeting aqp1-mRNA was designed
      and transfected into K562 cells by using Lipofectamine(TM) 2000 reagent. Phase
      contrast microscopy was used to analyze morphology changes of K562 cells. Cell
      viability was determined by MTT assay, and flow cytometry and DNA ladder analysis
      were carried out to identify siRNA-induced apoptosis. The expression levels of
      aqp1-mRNA at different transfection time were detected by RT-PCR. The results
      showed that the siRNA was successful by established. The transfected K562 cells
      displayed the significant apoptosis. The aqp1-siRNAs could obviously inhibit the
      activity of K562 cells. Cellular DNA fragmentation was observed in the siRNA
      group after transfection for 48 hours, the apoptosis rates at 24, 48 and 72 hours
      after transfection were 24.2%, 36.1% and 42.9% respectively. The aqp1-mRNA
      expression in the cells treated by aqp1-siRNA for 24, 48 and 72 hours were
      significantly reduced by 33%, 46% and 57% respectively. It is concluded that the
      aqp1-siRNA can efficiently and specifically inhibited the proliferation and
      inducing apoptosis of K562 cells. Gene aqp1 can be a potential target point for
      therapy of malignant tumor.

PMID- 20137116
TI  - [Effects of compound Zhe-Bei granule (CZBG) combined with doxorubicin on
      expression of membrane transport proteins in K562/A02 cell xenografts].
AB  - This study was purposed to investigate the effects of compound Zhe-Bei granule
      (CZBG) combined with doxorubicin on expressions of P-gp, MRP, LRP in K562/A02
      cell xenografts. Tumor xenograft model were established by injecting the
      multidrug resistant cell line K562/A02 in the axillary flank of BALB/c-nu-nu
      mice. CZBG-intragastric administration and doxorubicin-intraperitoneal injection
      in combination were given to the BALB/c-nu nude mice. The tumor xenografts were
      made into slice after the dissection, and the expression of P-gp, MRP, LRP in
      K562/A02 tumor xenografts in mice were investigated by immunohistochemical
      technique. The integral optical density (IOD) of P-gp, MRP, LRP in K562/A02 tumor
      xenografts were measured by Image Pro Plus 6.0. The results showed that as
      compared with the doxorubicin alone, the combination of the doxorubicin and CZBG
      with high, middle and low dosage could decrease IOD of P-gp, MRP in K562/A02
      tumor xenografts with statistical significance (p < 0.05). The LRP expression in
      K562/A02 tumor xenografts was not observed in five groups. It is concluded that
      the combination of CZBG with doxorubicin decreases the expressions of P-gp, MRP
      in K562/A02 tumor xenografts of mice.

PMID- 20137117
TI  - [Detection of ABL kinase domain point mutations in chronic myeloid leukemia
      patients receiving imatinib treatment].
AB  - This study was purposed to evaluate ABL tyrosine kinase point mutations in
      imatinib-treated chronic myeloid leukemia (CML) patients and their clinical
      significance. 51 bone marrow samples from 28 imatinib-resistant patients and 10
      newly diagnosed CML patients were collected. ABL kinase domain of bcr-abl allele
      was amplified by nested reverse transcription-polymerase chain reaction, followed
      by purifying, directly sequencing and sequence homology analysis of amplified
      products in order to determine the existence and type of point mutation. The
      results showed that the point mutations were found in 12 of 38 patients, and all
      the 12 ones progressed to advanced disease or death. 2 patients showed Met351Thr
      mutation, 7 patients showed Glu252His, 2 patients showed Glu279Lys, the other
      types were Glu255Val and Glu355Gly, each of which was tested in one patient. The
      incidence of the point mutation was 17.6%, 45.5% and 44.4% in chronic,
      accelerated and blast phase respectively. The incidences of point mutation in
      hematologically and genetically resistant patients were 50% (5/10) and 44.4%
      (8/18), and the 95% confidence interval (CI) was 12.3% - 87.7% and 19% - 69.9%
      respectively. It is concluded that ABL kinase point mutation is an important
      mechanism of imatinib resistance, monitoring the ABL kinase domain point mutation
      is helpful to estimating the prognosis and adjusting the therapeutic strategy.

PMID- 20137118
TI  - [Correlation between mTOR signaling transduction pathway and arsenic trioxide
      response].
AB  - This study was aimed to investigate the correlation between mTOR signaling
      transduction pathway and arsenic trioxide (ATO) effect. The expressions of pmTOR,
      pAKT and pP70S6K in K562/DNR treated with ATO for different time were detected by
      Western blot. The apoptosis rate of K562/DNR treated by ATO combined with
      LY294002 or rapamycin for 120 hours was assayed by flow cytometry. The results
      showed that the expression of pmTOR in K562/DNR cells treated with ATO for 60
      minutes or 120 minutes was higher than that in the control group (p < 0.01); the
      expressions of pAKT in the cells treated with ATO for 30 minutes or 60 minutes
      were higher than that in the control group (p < 0.01); the expression of pP70S6K
      in the cells treated with ATO for 60 minutes was higher than that in the control
      group (p < 0.01). The apoptosis rate of K562/DNR cells treated with combination
      of ATO and LY294002 or rapamycin were higher than that in the control group. It
      is concluded that the mTOR signaling pathway in K562/DNR cells is activated by a
      certain concentration of ATO, and mTOR signaling pathway inhibitors enhance ATO
      to trigger apoptosis in K562/DNR cells.

PMID- 20137119
TI  - [Induction of apoptosis of leukemic tumor cells in mouse model with G-quadruplex
      ligand Tel03].
AB  - This study was aimed to investigate the anti-leukemia activity of Tel03 in vivo.
      The K562 xenografted leukemia model was established and mice were divided
      randomly into three groups. Mice of different group were treated with PBS
      (control), 5 mg/kg Tel03 or 15 mg/kg Tel03 (ip, twice a week) respectively. Tumor
      volume, body weight and other behavior were observed regularly. Cell apoptosis
      was detected with TUNEL assay and the expression levels of Bcl-2 and Bax were
      detected by Western blot. The results indicated that Tel03 exerted anti-leukemia
      activity in mouse model. Tel03 significantly reduced tumor volume in Tel03
      treated group compared with control. In addition, 5 mg/kg Tel03 induced cell
      apoptosis without exerting apparent toxicity in mice. After Tel03 treatment, the
      expression of Bcl-2 was inhibited, however, the expression of Bax was up
      regulated. It is concluded that G-quadruplex ligand Tel03 can induce cell
      apoptosis in leukemia mouse model, and this agent may be a potential anticancer
      drug.

PMID- 20137120
TI  - [Apoptosis of jurkat cells induced by ursolic acid and its mechanism].
AB  - The aim of this study was to investigate the apoptosis effect of Jurkat cells
      induced by ursolic acid (UA) and its molecular mechanism so as to provide the
      theoretical basis for treatment of hematological malignancies by using UA. The
      cytotoxic effect of different concentration UA on Jurkat cells and inhibitory
      effect of caspase-9 inhibitor on cytotoxicity of UA were assayed by using WST-8
      method; the Jurkat cells treated with 20 or 40 micromol/L UA for 2 or 4 hours
      were collected and were stained by Annexin/PI, then the apoptosis rate of Jurkat
      cells was detected by flow cytometry; the Jurkat cells in logarithmic growth
      phase were collected after treatment with different concentrations of UA for
      different times, the cell protein was extracted, then the activation of caspase
      9, -3 and cytochrome C as well as phosphorylation level of Akt were determined by
      Western blot. The results indicated that the cytotoxic effect of UA on Jurkat
      cells was significant. UA induced apoptosis of Jurkat cells. Caspase-9, caspase-3
      and cytochrome C were activated, and the phosphorylation of Akt was inhibited in
      the Jurkat cell apoptosis process induced by UA. It is concluded that the UA
      shows significant cytotoxic effect on Jurkat cells, UA can induce apoptosis of
      Jurkat cells through the mitochondria pathway. The mechanism may be associated
      with the inhibition of Akt phosphorylation.

PMID- 20137121
TI  - Effects of magnetic nanoparticle of Fe3O4 on apoptosis induced by Gambogic acid
      in U937 leukemia cells.
AB  - This study was aimed to explore the potential therapy of Gambogic acid (GA)
      combined with magnetic nanoparticle of Fe3O4 (Fe3O4-MNP) on leukemia. The
      proliferation of U937 cells and the cytotoxicity were evaluated by MTT assay.
      Cell apoptosis was observed and analyzed by microscopy and flow cytometry
      respectively. The expressions of gene and protein were detected by quantitative
      real-time polymerase chain reaction and Western blot respectively. The results
      showed that GA enhanced the cytotoxicity for U937 cells in dose- and time
      dependent manners. The Fe3O4-MNP itself had not cytotoxicity, but could enhance
      the inhibitory effect of GA on proliferation of U937 cells. The apoptotic rate of
      U937 cells induced by combination of GA with Fe3O4-MNP was higher than that by GA
      alone. The typical apoptotic features of cells treated with GA and Fe3O4-MNP were
      observed. The expression levels of caspase-3 and bax after co-treatment of GA and
      Fe3O4-MNP were higher than that exposed to GA or Fe3O4-MNP alone, but the
      expressions of bcl-2, NF-kappaB and survivin were down-regulated. It is concluded
      that Fe3O4-MNP can promote GA-induced apoptosis in U937 cells, and the
      combination of GA with Fe3O4-MNP may be a safer and less toxic new therapy for
      leukemia.

PMID- 20137122
TI  - [Effects of hypoxia-inducible factor inhibitor on expression of HIF-1alpha and
      VEGF and induction of apoptosis in leukemic cell lines].
AB  - This study was purposed to investigate the effect of a hypoxia-inducible factor
      inhibitor (YC-1) on expression of hypoxia-inducible factor 1alpha (HIF-1alpha)
      and vascular endothelial growth factor (VEGF) as well as induction of apoptosis
      in leukemic cell lines. RT-PCR was used to determine the levels of HIF-1alpha
      mRNA and VEGF mRNA in K562, U937 and Jurkat cells. After treatment of U937 cell
      with 4 micromol/L YC-1, cell apoptosis was assayed by DAPI staining under
      fluorescent microscope and flow cytometry with Annexin V-FITC/PI staining; the
      expression levels of HIF-1alpha mRNA and VEGF mRNA were measured with RT-PCR; the
      expression levels of HIF-1alpha, VEGF, BAX, BCL-2 and caspase-3 proteins were
      measured by Western blot. The results showed that HIF-1alpha mRNA and VEGF mRNA
      were expressed in all three leukemia cell lines. After treatment of U937 cell
      with 4 micromol/L YC-1 for 0, 8, 16 and 24 hours, the changes of morphologic
      features of U937 cells could be observed under fluorescent microscope and the
      apoptotic rates significantly increased in time-dependent manner, they were (4.87
      +/- 0.70)%, (27.27 +/- 2.00)%, (51.53 +/- 2.81) and (60.5 +/- 3.20)%
      respectively, the expression levels of VEGF mRNA reduced, while the expression
      levels of HIF-1alpha mRNA had no obviously changes.Furthermore, the expression of
      HIF-1alpha, VEGF and BCL-2 decreased, while the expression of BAX and caspase-3
      increased, the ratio of BAX/BCL-2 increased in time-dependent manner (r = 0.973,
      p < 0.01). It is concluded that HIF-1alpha mRNA and VEGF mRNA are all expressed
      in in K562, U937 and Jurkat cells, YC-1 has significant effect on down-regulating
      the protein expression of HIF-1alpha and VEGF, and induces the apoptosis in U937.
      The mechanism of apoptosis in leukemic cells may involve in up-regulating BAX/BCL
      2 ratio and expression of protein caspase-3.

PMID- 20137123
TI  - [Effect of PDMP, a glucosylceramide synthase inhibitor, on reversion of
      daunorubicin resistance in human leukemia cell line K562/A02].
AB  - This study was purposed to investigate the reversal effect of glucosylceramide
      synthase (GCS) inhibitor D, L-threo-1-phenyl-2-decanoylamino-3-morpholino-1
      propanol (PDMP) hydrochloride, on multidrug resistance in K562/A02 cells and its
      mechanism. The IC(50) (the half maximal inhibitory concentration) of PDMP was
      measured by MTT method. Cell apoptosis and intracellular daunorubicin (DNR)
      concentration were detected by flow cytometry. The expression of GCS and mdr1
      genes were assayed by semi-quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR) and Western blot. The results showed that the IC(50) of DNR in
      K562 and K562/A02 cells were 0.23 +/- 0.02 and 7.15 +/- 0.24 microg/ml
      respectively. When the concentration of PDMP was equal to or less than 20
      micromol/L ( < / = 20 micromol/L), the obviously inhibitory effect on
      proliferation of K562 and K562/A02 cells was not observed, but both 20 micromol/L
      and 10 micromol/L PDMP could enhance the sensitivity of K562/A02 cells to DNR (p
      < 0.01) and the reversal multiples were 2.59 and 1.69 respectively. After
      treating with 20 micromol/L and 10 micromol/L PDMP for 48 hours, the
      concentration of DNR in K562/A02 cells increased (p < 0.05) and the apoptotic
      rate also was elevated (p < 0.01). The expressions of GCS and mdr1 genes were
      down-regulated at mRNA and protein levels after treating K562/A02 cells with 20
      micromol/L PDMP for 48 hours. It is concluded that PDMP can enhance the
      sensitivity of K562/A02 cells to DNR by increasing cell apoptosis rate and
      accumulation concentration of DNR in cells, which may be related to down
      regulated expressions of GCS and mdr1 genes.

PMID- 20137124
TI  - [Construction of shRNA eukaryotic expression vectors of pkm2 gene and their
      effect on drug resistant cell line of acute promyelocytic leukemia].
AB  - This study was aimed to construct the shRNA eukaryotic expression vectors of M2
      pyruvate kinase gene (pkm2) and to investigate the effects of pkm2 gene
      interference on the drug resistance of acute promyelocytic leukemia (APL) cells
      in vitro. Three specific shRNAs of pkm2 gene were designed and cloned into PBSU6
      vector containing a U6 promotor. The constructed plasmids were identified and
      proved by the restriction sequence analysis. Then the effect of pkm2-shRNA on the
      protein expression of endogenous PKM2 was detected in NB4R2 cells, a drug
      resistant cell line of APL by Western blot. The alteration of NB4R2 cell
      differentiation with the interference of pkm2 gene was also validated by
      nitroblue tetrazolium (NBT) reduction test. The results showed that three
      specific shRNA eukaryotic expression vectors targeting pkm2 were successfully
      constructed. The efficiency of pkm2 gene silence was proved at protein level. The
      interference of pkm2 gene could significantly enhance the cell differentiation in
      the drug resistant NB4R2 cell line. It is concluded that the DNA vector
      containing pkm2 targeting shRNA remarkably promotes the differentiation of NB4R2
      cells, showing the prospects of developing the gene target drug.

PMID- 20137125
TI  - [Reversal of multidrug-resistance in human leukemia cell line K562/A02 by
      tyrosine kinase inhibitors].
AB  - This study was aimed to investigate the reversal effect of tyrosine kinase
      inhibitors (TKI) Imatinib and Nilotinib on multidrug-resistant cell line
      K562/A02. The expression levels of mdr-1 mRNA and bcr-abl mRNA were assayed by RT
      PCR. The protein levels of P-glycoprotein (P-gp) and P210 were detected by
      Western blot. The daunorubicin (DNR) accumulation in K562/A02 cells were analyzed
      by flow cytometry (FCM). The results showed that the 0.0625 micromol/L Imatinib
      or 5 nmol/L Nilotinib alone had no cytotoxic effect on the inhibition of K562/A02
      cells. When K562/A02 cells were treated with Imatinib or Nilotinib alone for 48
      hours, the expressions of mdr-1 mRNA, der/abl mRNA, P-gp and P210 protein were
      all down-regulated, furthermore the effect of Nilotinib was stronger than that of
      Imatinib. The detection of fluorescence intensity revealed that the DNR
      concentration in K562/A02 cells treated with Imatinib or Nilotinib alone for 48
      hours were 7.85% and 12.02% of K562 cells respectively. It is concluded that the
      tyrosine kinase inhibitors show great effect reversing drug resistance of cells,
      moreover, the effect of Nilotinib is stronger than that of Imatinib.

PMID- 20137126
TI  - [Preliminary study on the effect of TRAIL on adhesion and apoptosis of multiple
      myeloma cell line RPMI8226 and its mechanism].
AB  - The present study was purposed to investigate the inhibition effect of tumor
      necrosis factor-related apoptosis inducing ligand (TRAIL) on growth of RPMI8226
      cells and adhesion between RPMI8226 cells and bone marrow stroma cells (BMSC),
      and to explore its mechanism as well. The inhibition effects of TRAIL on cells
      growth and adhesion were assayed by MTT; cell apoptosis was detected by Annexin V
      and PI; expression of genes bax, bcl-2, mcl-1, CARP1, CARP2, XIAP and cFLIP were
      determined by semi-quantitative RT-PCR; apoptosis-related protein expression was
      detected by Western blot. The results showed that TRAIL inhibited the
      proliferation of RPMI8226 cells in dose- and time-dependent manners. TRAIL
      induced apoptosis in RPMI8226 cells, the expression level of genes bcl-2, mcl-1,
      CARP1, CARP2, XIAP and cFLIP decreased, while the expression level of Bax
      increased, but the expression level of caspase-3 and NF-kappaB P65(RelA) proteins
      decreased. Moreover, TRAIL up-regulated the expression level of adherent molecule
      CXCR4 in RPMI8226 cells significantly. It is concluded that TRAIL up-regulated
      the expression level of adherent molecule CXCR4 in RPMI8226 cells significantly,
      and induced the apoptosis of RPMI8226 cells. Growth inhibition effect of TRAIL on
      RPMI8226 cells is in dose- and time-dependent manners.

PMID- 20137127
TI  - [Role of bone marrow microenvironment in regulation of AP-1 gene expression in
      multiple myeloma cells].
AB  - This study was aimed to investigate the role of bone marrow microenvironment in
      the regulation of activator protein 1 (AP-1) expression in multiple myeloma (MM)
      cells. The primary myeloma cells (CD138(+) cells) from 8 patients with MM were
      sorted by using immunomagnetic beads and were cocultured with osteoclasts in
      alpha-MEM supplemented with 10% fetal bovine serum, antibiotics, RNAKL (50 ng/ml)
      and macrophage colony-stimulating factor (25 ng/ml) for 10 to 14 days at 2.5 x
      10(6) cells/ml. The expression levels of genes c-jun, junD fos and fosB were
      detected by real-time PCR. The results showed that the osteoclasts were observed
      after coculture of mononuclear cells in peripheral blood of MM patients with
      osteoclasts for 10 - 14 days. As compared with control (without coculture with
      osteoclasts), the viability of MM cells cocultured with osteoclasts obviously
      increased, the expression levels of c-jun, junD, fos and fosB decreased to 25.7% 
      1.66%, 68.49% - 8.54%, 10.35% - 0.19% and 36.63% - 3.44% of the control
      respectively. It is concluded that the bone marrow microenvironment can inhibit
      the expression of c-jun, junD, fos and fosB promote myeloma cell proliferation
      and maintain cell survival.

PMID- 20137128
TI  - [Establishment and identification of mouse lymphoma cell line EL4 expressing red
      fluorescent protein].
AB  - This study was purposed to construct a lentiviral vector encoding red fluorescent
      protein (DsRed) and transfect DsRed into EL4 cells for establishing mouse
      leukemia/lymphoma model expressing DsRed. The bicistronic SIN lentiviral transfer
      plasmid containing the genes encoding neo and internal ribosomal entry site-red
      fluorescent protein (IRES-DsRed) was constructed. Human embryonic kidney 293FT
      cells were co-transfected with the three plasmids by liposome method. The viral
      particles were collected and used to transfect EL4 cells, then the cells were
      selected by G418. The results showed that the plasmid pXZ208-neo-IRES-DsRed was
      constructed successfully, and the viral titer reached to 10(6) U/ml. EL4 cells
      were transfected by the viral solution efficiently. The transfected EL4 cells
      expressing DsRed survived in the final concentration 600 microg/ml of G418. The
      expression of DsRed in the transfected EL4 cells was demonstrated by fluorescence
      microscopy and flow cytometry. In conclusion, the EL4/DsRed cell line was
      established successfully.

PMID- 20137129
TI  - [Changes of HLA-DR15 and immunoglobulin, T lymphocyte subsets in patients with
      aplastic anemia, myelodysplastic syndrome and their significance].
AB  - The objective of this study was to detect the expression frequency of HLA-DR15 in
      patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), to
      investigate the relation of expression frequency with diseases and to analyze the
      relationship between immunoglobulin, T lymphocyte subsets and HLA-DR15. HLA-DR15
      expression was detected by PCR-SSP; immunoglobulin was detected by immune
      turbidimetry; T cell subsets were detected by flow cytometry. The results showed
      that the expression rates of HLA-DR15 in AA and MDS as well as normal control
      groups were 78.6%, 63.2% and 24.6% respectively. The difference between AA, MDS
      and the normal control groups was statistically significant (p < 0.01). OR (odds
      ratios) values of AA and MDS groups were 11.262, 4.710 respectively. Compared
      with normal control group, expression rate of HLA-DR15 in hematologic malignancy
      group was not significantly different. The immunoglobulin level and abnormal T
      cell subsets in AA and MDS groups were statistically different between HLA-DR15
      positive and negative groups (p > 0.05). It is concluded that the frequency of
      HLA-DR15 antigen in AA and MDS patients is significantly higher than that in
      normal control and hematologic malignancy group. OR value>1 showed a positive
      correlation between the diseases and HLA-DR15. HLA-DR15 is a susceptible gene in
      AA and MDS. The abnormalities of immunoglobulin level and ratios of T cell
      subsets in AA and MDS are common, but are not associated significantly with the
      expression of HLA-DR15.

PMID- 20137130
TI  - [Mass spectrography analysis of differential proteome in childhood TEL/AML1
      positive acute lymphoblastic leukemia].
AB  - The study was aimed to establish differential proteomic expression analysis of
      two dimensional electrophoresis and mass spectrography, and to further explore
      the mechanisms of nosogenesis in childhood TEL/AML1(+) acute lymphoblastic
      leukemia. On the basis of initial leukocyte count and prognostic factors,
      patients enrolled in this study were divided into three risk groups (early
      relapse, high leukocyte count and standard risk groups). The proteins of leukemic
      cells from patients at diagnosis were separated by two-dimensional gel
      electrophoresis. Spot detection, quantification and alignment were performed with
      the PDQuest 7.3.0 image analysis software. Differentially expressed spots were
      analyzed by mass spectrometry for peptide mass finger (PMF) data. The results
      showed that the significant difference of protein expression profile existed in 3
      groups of childhood TEL/AML1-positive acute lymphoblastic leukemia. Compared with
      the high leukocyte count and standard risk groups, 71 protein spots disappeared;
      93 new protein spots were found; 37 protein spot expressions were up-regulated;
      23 protein spots were down-regulated in early relapse group. Compared the high
      leukocyte count group, 6 protein spots disappeared, 56 new protein spots were
      found, 7 protein spot expression were up-regulated, 19 protein spot expressions
      were down-regulated in standard risk group. The identification of 40 differential
      protein spots by using mass spectrometry revealed some proteins in 3 groups such
      as tropomyosin, lactotransferrin, lactate dehydrogenase A, CRMP1 protein,
      alphaenolase, AKR1B1, calnexin precursor, heat shock protein (HSP86/HSP89/HSP90),
      annexin VI, G22P1 and so on. Among them the HSP86/HSP89/HSP90 highly expressed
      only in early reapse group, the lactotransferrin, alphenolase and G22P1
      expressions were up-regulated in early relapse group. It is concluded that the
      protein expression in early relapse group is significant different from the
      others. Some proteins may be further used in research on leukemia mechanisms. In
      addition, these analyses may promote the identification of new targets for
      individualized treatment approaches.

PMID- 20137131
TI  - [Comparison of effect between homologous recombinant gene knockout and siRNA gene
      silence in cell lines].
AB  - The objective of this study was to compare the effects between knocking-out Sam68
      gene by homologous recombination method and silencing the gene by siRNA silencing
      technique in DT40 cell line. Gene targeting technique was used to isolate Sam68
      gene-deleted chicken DT40 cells. Meanwhile, Sam68 gene silencing cells was
      obtained by using stable expression of siRNA plasmid pSilencer-Sam68. Then, the
      function of these two cell lines were analyzed by comparing with wild-type DT40
      cell line. The results showed that the growth retardation in Sam68 gene knocked
      out cell line was observed due to elongation of the G2/M phase, but which could
      not be found in Sam68 gene silencing cell line. It is concluded that in
      accordance with study of protein function in living cells, use of gene knockout
      technique for cell line can provide the experimental results more real than those
      resulting from gene silence technique.

PMID- 20137132
TI  - [Construction and identification of Mdr-1-shRNA eukaryotic expression vector].
AB  - This study was purposed to construct and identify the short hairpin RNA (shRNA)
      eukaryotic expression vector for targeting gene mdr-1 which may play an important
      role in K562/A02. Short hairpin RNA (shRNA) aiming at the target sequence was to
      synthesized, the 3491-3509, 1539-1557and 3103-3121 nucleotide of mdr-1 mRNA were
      selected as targets. The selected nucleotides were cloned in the plasmid
      pGCSilencer-U6-neo-GFP respectively, and the resultant recombinant plasmids were
      named as pGY1-1, pGY1-2 and pGY1-3. The sequences of the recombinant plasmids
      were identified by DNA sequencing and PCR electrophoresis. The recombinant
      plasmids were transfected into the cell line K562/A02 by lipofection. After being
      transfected for 48 hours, the inhibition of mdr-1 mRNA was detected by real time
      PCR, and P-gp expression was detected by Western blot. The results showed that
      the specific oligonucleotide was cloned into the vector successfully, and the
      expression of mdr-1 mRNA and P-gp in K562/A02 cells was reduced after
      transfecting the recombinant plasmid, as compared to the control group. It is
      concluded that the shRNA eukaryotic expression vector has been successfully
      established which can inhibit the expression of mdr-1 mRNA, setting up the basis
      to futher explore the effects of mdr-1 on cell line of K562/A02.

PMID- 20137133
TI  - [Killer immunoglobulin-like receptor gene genotype and expression pattern in
      healthy people].
AB  - The aim of study was to clarify the repertoire of killer immunoglobulin-like
      receptor (KIR) at the level of DNA and RNA in healthy persons and to compare KIR
      on genotypes and expression patterns. KIR genotypes including KIR2DL1, 2DL2,
      2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1 and
      3DP1 were analyzed by PCR. The phenotypes including KIR2DL1, KIR2DL2, KIR2DL3,
      KIR3DL1, KIR2DS1, KIR2DS3, KIR2DS2/4 gene were determined by RT-PCR. The results
      showed that the genes of KIR2DL1, KIR2DL3, KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1
      could be detected in all healthy persons, NK-92MI cells and Molt4 cells, but all
      corresponding receptors were not expressed by Molt4 T cells. Only partial
      transcripts of KIR2DL1, KIR2DL3 and KIR2DS2/4 were detectable in NK-92MI cells.
      If genotypes of KIR2DL1, 2DL2, 2DL3, 2DS1, 2DS2, 2DS3 and 2DS4 were detected in
      healthy persons, almost all transcripts of corresponding receptors were expressed
      in peripheral blood NK cells. The expression levels of KIR were different. In
      conclusion, the repertoires of KIR are individually specific. The expression
      pattern of KIR is also specific, the expression levels of different KIRs are
      different in one individual, and the expression levels of the same KIR are also
      different in different individuals.

PMID- 20137134
TI  - [Influence of magnetic Fe3O4 nanoparticle on functions of lymphocytes and
      macrophages in mice].
AB  - This study was purposed to investigate the effects of magnetic nanoparticle of
      Fe3O4 (Fe3O4-MNPs) on murine immune system. ICR mice were assigned randomly into
      four groups which were treated with normal saline, low, middle and high dose of
      MNP-Fe3O4 respectively. The mice were killed after being exposed by intragastric
      administration for 2 weeks. The ratios of spleen weight to body weight,
      lymphocyte transformation rate in spleen suspension and phagocytic index of
      macrophage in abdominal cavity were detected. The results showed that the ratios
      of spleen weight to body weight in Fe3O4-MNP groups were not significantly
      different in comparison with the control (p > 0.05). The lymphocyte
      transformation rate in spleen suspension in Fe3O4-MNP groups were all higher than
      that in control group (-0.1775 +/- 0.0246), especially in the middle dose group
      (0.1833 +/- 0.0593) (p < 0.05), and the phagocytic index of macrophages in
      abdominal cavity of middle dose group (0.2051 +/- 0.0213) was higher than that of
      control group and other two Fe3O4-MNP group (low dose 0.1538 +/- 0.0100, high
      dose 0.1511 +/- 0.0184) (p < 0.05). It is concluded that suitable dose of Fe3O4
      MNP can enhance the cellular immune activity and phagocytic function of
      macrophages of mice.

PMID- 20137135
TI  - [Distribution and interaction of bone marrow mesenchymal stem cells and cord
      blood CIK/NK cells infused via different ways at different time periods in
      NOD/SCID mice].
AB  - The study was aimed to explore the distribution and interaction mechanism of
      human bone marrow mesenchymal stem cells (MSC) and cord blood cytokine-induced
      killer (CIK)/natural killer (NK) cells infused via different ways at different
      times in NOD/SCID mice. 5 microl 1, 1'-dioctadecyl-3, 3, 3', 3'
      tetramethylindocarbocyanine perchlorate (DiI) dye(red) was added in suspension of
      MSC per ml, and 1 microl carboxyfluorescein diacetate, succinimidyl ester(CFDA
      SE) dye(green) was added in suspension of CIK/NK cells per ml. The amounts of MSC
      and CIK/NK cells infused in each 6 NOD/SCID mouse were 1 x 10(6) (0.1 ml) and 1 x
      10(7) (0.1 ml) respectively. All mice were divided into 4 groups, each group
      consisted of 6 mice. Group A: MSC (intravenous infusion, iv) + CIK/NK cells (iv)
      at the same time, group B: MSC (iv) + CIK/NK cells (iv) at 48 hours after
      infusion of MSC; group C: MSC (intramedullary infusion, im) + CIK/NK cells (iv)
      at the same time; group D: MSC (im) + CIK/NK cells (iv) at 48 hours after
      infusion of MSC. 3 NOD/SCID mice were sacrificed per batch at 24 hours and 48
      hours after infused CIK/NK cells. Frozen sections of liver, spleen, lung and
      kidney were prepared, and then followed by counting the amounts of red and green
      fluorescence cells under fluorescence microscope, and calculating the ratio of
      MSC to CIK/NK cells for reflecting the interaction of MSC and CIK/NK cells in
      mice, and for showing the suppressive intensity of MSCs on CIK/NK cells. The
      results showed that the sums of average ratios of MSC to CIK/NK cells in lung,
      liver and spleen of group A and B were higher than that in group C and D at 24
      hours and 48 hours respectively after infusing CIK/NK cells. The sum of average
      ratios of MSC to CIK/NK cells in group A was slightly higher than that in group B
      at 24 hours and 48 hours after infusing CIK/NK cells, but there was no
      significant difference between them. The sum of average ratios of MSC to CIK/NK
      cells in lung, liver and spleen in group C was slightly lower than that in group
      D at 24 hours after infusing CIK/NK cells, but reversed at 48 hours later and
      there was no significant difference between them. The sums of average ratios of
      MSC to CIK/NK cells in lung, liver and spleen in group A, B, C and D were all
      higher than those in kidney at 24 and 48 hours respectively after infusing CIK/NK
      cells. It is concluded, the MSC and CIK/NK cells may interact if they are infused
      via the same way and at the same time, the location where the suppression of MSC
      on CIK/NK cells occur in vivo may be reticulo-endothelial systems in lungs and
      livers.

PMID- 20137136
TI  - [Changes of differentiation and gene expression of CD133+ cells in human
      umbilical cord blood induced by SCF and bFGF].
AB  - This study was aimed to investigate the changes of differentiation and gene
      expression of CD133(+) cells in human umbilical cord blood induced by stem cell
      factor (SCF) and basic fibroblast growth factor (bFGF) in vitro, and to explore
      the biological characteristics of CD133(+) cells so as to provide experimental
      basis for potential use in regenerative medicine. The human umbilical cord blood
      CD133(+) cells were isolated from umbilical cord blood and purified by MACS
      magnetic selection. The CD133(+) cells were cultured in DMEM/F12 medium
      containing SCF, bFGF and B27 for 10 to 15 days. The total RNA of these cells was
      extracted before and after culture, and the analysis of related gene expression
      levels of these cells was performed using oligonucleotide microarrays. The
      results showed that out of 263 genes 21 genes were obviously up-regulated after
      culture than that before culture, whereas 7 genes were found to be significant
      down-regulated as compared with fresh-separated CD133(+) cells. These genes were
      involved in stem cell specific markers, cell cycle regulators, stem cell
      differentiation markers and signaling pathways that are important for stem cell
      maintenance. It is concluded that SCF and bFGF can induce differentiation of
      human cord blood CD133(+) cells through up- or down-regulation of specific genes.
      This study provides gene expression information for SCF and bFGF-induced human
      cord blood CD133(+) cells and contributes to understand the effect of SCF and
      bFGF on proliferation and differentiation CD133(+) cells at gene level, and
      promotes therapeutic applications of the CD133(+) cells induced by SCF and bFGF.

PMID- 20137137
TI  - [Mesenchymal stem cells exist in the compact bones from four species of mammals].
AB  - The biological properties of cultured mesenchymal stem cells (MSC) have been
      intensively investigated, while there is still a paucity of information about the
      definite in vivo sites that harbor these stem cells due to the lack of specific
      surface markers. Previous data have demonstrated that human and murine MSC can be
      isolated from the compact bones. To investigate if it is the case for other
      species, the femurs from Wistar rats, Beagles, C57 mice and New Zealand rabbits
      were collected, minced and digested with collagenase type I. The digested bone
      fragments were seeded into the medium for human bone marrow culture after removal
      of the suspended cells in the digestion. The results showed that the fibroblast
      like cells were observed to migrate from the bone fragments after several days of
      culture, and they gradually formed an adherent confluent layer. The adherent
      cells could be passaged and expressed homogenously the mesenchymal cell marker
      vimentin. Differentiation assays showed that these cells had the capacity to
      differentiate into osteoblasts and adipocytes. In conclusion, the results here
      provide new information for the further investigations on the in vivo biological
      features of MSC in the context of the simplicity of the compact bone structure.

PMID- 20137138
TI  - [Transfusion of mesenchymal stem cells combined with haploidentical HSCT improves
      hematopoietic microenvironment].
AB  - The aim of this study was to investigate the role of mesenchymal stem cells in
      the hematopoietic reconstitution of patients who had received haploidentical
      allogeneic hematopoietic stem cell transplantation (hi-allo-HSCT). 15 patients
      who underwent treatment with both MSCs and HSCs, were selected as study group,
      while 20 patients receiving only HSCT were taken as control. Bone marrow samples
      were obtained from iliac crest aspirates at several times after HSCT for the
      isolation, purification and expansion of MSCs. The confluent ratio and time were
      measured and compared with those of the control. The peripheral blood samples
      were obtained from patients, then absolute neutrophil and platelet counts were
      assayed. From day 4 before transplantation to day 28 after transplantation, serum
      was obtained every four days from patients of the two groups, and then 3
      cytokines as SDF-1alpha, TPO and IL-11 were detected by ELISA. The results
      indicated that as compared with the control group, the ratio of primary confluent
      layer formation of MSCs in study group was obviously higher (27.3%) (p < 0.01),
      and the confluence time in culture was significantly less (p < 0.05). In the
      study group, the concentration of SDF-1alpha amounted to peak value (2975.19 +/-
      681.56 pg/ml) on the 8th day after HSCT, which was obviously higher than that
      before HSCT (2403.70 +/- 522.39 pg/ml, p < 0.05), whereas in the control, the
      concentration of highest point of SDF-1alpha reached to peak valve (2280.60 +/-
      701.25 pg/ml) on the 16th day after HSCT, which was less than that before HSCT
      (2701.46 +/- 483.21 pg/ml, p < 0.05). The concentration of TPO and IL-11 was
      higher in study group compared with the control from day 16 to 28 after HSCT (p <
      0.05). It is concluded that the transfusion of MSCs combined with hi-all-HSCT may
      improve the injured state of the hematopoietic microenvironment in bone marrow of
      patients during allo-HSCT.

PMID- 20137139
TI  - [Allogeneic stem cell transplantation for 75 cases of acute myeloid leukemia in
      complete remission: outcome and prognostic analysis].
AB  - This study was purposed to evaluate the outcome of patients with acute myeloid
      leukemia (AML) who received allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) in complete remission, and to study the prognostic factors. 75 cases
      of AML in complete remission receiving allo-HSCT from January 2000 to December
      2007 were retrospectively analyzed. Major end points of study included overall
      survival (OS), disease free survival (DFS), relapse rate and transplantation
      related mortality (TRM). The results showed that 3-year OS and DFS of the study
      population reached to 58.4% and 53.9% respectively, and the relapse rate and TRM
      leaded to 16.9% and 29.9% respectively. Incidence of acute GVHD was 59.6%, with
      18.7% II-IV aGVHD. Different prognosis was observed between HSCT recipients of
      alternative donor and HLA-matched related donor (MRD) (3-year DFS was 34.3% vs
      60.0%, p = 0.019), between patients of refractory leukemia and the control (3
      year DFS was 35.7% vs 58.2%, p = 0.048), between recipients with and without
      severe aGVHD (3-year DFS was 35.7% vs 54.4%, p = 0.059). Further analysis
      revealed significantly high TRM in recipients receiving allo-HSCT of alternative
      donor (p = 0.033) and high rate of severe aGVHD (p = 0.010). Multivariate
      analysis revealed three negative prognostic factors: donor availability
      (alternative vs MRD) (p = 0.049, RR = 2.09, 95%CI 1.01 - 4.36), refractory
      leukemia (p = 0.038, RR = 2.33, 95%CI 1.05 - 5.20) and severe aGVHD (p = 0.040,
      RR = 2.33, 95%CI 1.04 - 5.20). It is concluded that allo-HSCT is a choice for the
      AML case at complete remission and TRM is the major cause of the transplantation
      failure. Donor availability, refractory leukemia and severe aGVHD are confirmed
      as risk factors of poor prognosis for allo-HSCT patients with AML in CR.

PMID- 20137140
TI  - [Alteration of chemokines after allogeneic hematopoietic stem cell
      transplantation and its clinical significance].
AB  - The objective of this study was to analyze the relationship between some
      chemokines and the pathogenesis of GVHD and to find some biomarkers with
      diagnostic significance through observing and comparing the changes of some
      chemokine levels in samples from patients with or without aGVHD after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). 26 plasma samples were
      obtained from 26 patients undergoing allo-HSCT at various time points after
      transplantation, of which 13 samples from patients with aGVHD were served as
      investigating group and 13 samples from patients without GVHD after Allo-HSCT
      were used as control group. The patient characteristics between the two groups
      were compared, the levels of 40 chemokines in these samples were detected by
      ELISA, the changes of chemokine levels in samples of 2 groups were analyzed by
      means of significance analysis microarray (SAM), clustering method and c-test.
      The results showed that there were significant differences in levels of 6
      chemokines including HCC-1, MIF, IP-10, ITAC, TARC and NAP-2 between 2 groups, in
      which the level of MIF in plasma samples after HSCT was the highest, the
      difference of TARC level between 2 groups was over 10-fold. It is concluded that
      the level changes of chemokines mentioned above can be used as a indicator of
      GVHD presence, but their pathogenetic role in occurrence of aGVHD remains to be
      determined.

PMID- 20137141
TI  - [Allogeneic hematopoietic stem cell transplantation combined with imatinib for
      treatment of Philadelphia chromosome positive acute lymphoblastic leukemia].
AB  - The study was purposed to explore the efficacy of allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) combined with Imatinib for treatment of
      Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+)ALL)
      patients. From 2007 to 2008, 3 patients with Ph(+)ALL were treated with
      allogeneic hematopoietic stem cell transplantation and Imatinib, and the follow
      up ended at Oct 21(st) 2009. 1 patient received HSCT from matched sibling donor
      and 2 patients from haploidentical related donors. All 3 patients achieved
      complete remission before transplantation and were treated with Imatinib for
      distinct time at different periods before and/or after transplantation. The level
      of bcr/abl mRNA was monitored using real-time PCR. The results showed that all 3
      patients achieved stable engraftments without severe transplantation related
      complications. The level of bcr/abl mRNA declined and achieved zero level
      finally. In conclusion, the allo-HSCT combined with Imatinib is an effective
      therapy regimen for Ph(+)ALL patients.

PMID- 20137142
TI  - [Clinical research on reconstitution of CD4+CD25+ T cells after haploidentical
      bone marrow transplantation].
AB  - The aim of this study was to investigate the reconstitution of CD4(+)CD25(+) T
      cells after haplo-identical bone marrow transplantation (hiBMT) and its
      correlation with graft versus host disease (GVHD) and relapse. Peripheral blood
      samples from 27 patients after hiBMT were harvested and the percentage and
      absolute counts of CD4(+)CD25(+) T cells were detected by flow cytometry. The
      correlations of GVHD occurrence and disease relapse with the reconstitution of
      CD4(+)CD25(+) T cells were analyzed. The results showed that the percentage of
      CD4(+)CD25(+) T cells of peripheral blood samples increased significantly after G
      CSF priming. At day 30 after hiBMT, CD4(+)CD25(+) T cells were recovered to the
      20% of normal level, followed by a slowly process in 3 months, and up to one half
      of the normal level at 180 days. There was no evidence to prove relationship
      between CD4(+)CD25(+) T cells and acute GVHD, while CD4(+)CD25(+) T cells were
      increased significantly in the chronic GVHD group. The absolute count of
      CD4(+)CD25(+) T cells showed no relations with relapse of leukemia during the
      first year after hiBMT. In conclusions, chronic but not acute GVHD was in
      relation to the reconstitution of CD4(+)CD25(+) T cells based on the anti-CD25
      antibody therapy model for the prevention of GVHD after hiBMT. Further
      investigation is needed to clarify whether the relapse of leukemia after hiBMT is
      related to the reconstitution of CD4(+)CD25(+) T cells.

PMID- 20137143
TI  - [Influence of donor Treg cells on GVHD and GVL effects after allogeneic bone
      marrow transplantation in mice].
AB  - In order to explore the influence of purified donor regulatory T cells (Treg)
      infused after allogeneic bone marrow transplantation (allo-BMT) on GVHD and GVL
      effect in mice, an EL4 leukemia allo-BMT model of BALB/c-->C57BL/6 mice was
      established. The CD4(+)CD25(+)T cells were purified by positive selection using
      MACS. The recipients were injected with CD4(+)CD25(+)T cells or CD4(+)CD25(-)T
      cells within 4 hours respectively along with allo-BMT. Survival time, clinical
      GVHD score or histopathological features were observed after allo-BMT. The
      results showed that the mean survival time in leukemia control group was (17.9 +/
      0.7) days and all mice died of leukemia. The mean survival times in
      transplantation control group and CD4(+)CD25(-)T group were (23.2 +/- 1.6) and
      (22.3 +/- 1.9) days. Histopathological analysis in several target organs (skin,
      liver and small intestine) confirmed the presence of severe GVHD. The mean
      survival time in Treg group was (47.3 +/- 6.5) days. 70% of recipients were alive
      until day 60 without features of GVHD or tumor progression. Clinical GVHD scores
      in Treg group significantly decreased as compared to transplantation control
      group and CD4(+)CD25(-)T group (p < 0.05). It is concluded that allo-BMT combined
      with injection of donor CD4(+)CD25(+)Treg cells can efficiently prevent
      recipients from lethal GVHD with preserving GVL effect during allo-BMT.

PMID- 20137144
TI  - [Combined deficiency of factors V and VIII caused by a novel compound
      heterozygous mutation of gene Lman1].
AB  - Combined deficiency of factor V and VIII (F5F8D) is a rare, autosomal recessive
      disorder caused by mutations of either lman1 or mcfd2. To identify mutations of
      these two genes in a Chinese F5F8D family, the samples of peripheral blood were
      collected from the proband and her parents. Coagulation tests were carried out,
      including activated partial thromboplastin time (APTT), prothrombin time (PT),
      thrombin time (TT), fibrinogen (Fg) and coagulate activity of FV, FVIII (FV:C,
      FVIII:C). The genomic DNA was extracted, then all the exons and intron/exon
      boundaries of these two genes were amplified by polymerase chain reaction (PCR).
      The products were finally analyzed by direct sequencing. The results showed that
      the proband's APTT, PT, TT, Fg, FV:C and FVIII:C were 82.2 sec, 19.6 sec, 18.6
      sec, 2.9 g/L, 7.1% and 18.7% respectively, while those parameters of the parents
      were all within the normal range. Two pathogenic mutations were identified in
      lman1 gene of the proband: one was the heterozygous c.912_913insA in exon 8
      resulting in a frameshift of p.Glu305fsX20; the other was the heterozygous
      c.1366C > T in exon 11 resulting in p.Arg456X. The proband's father and mother
      were heterozygous for c.1366C > T and c.912_913insA respectively. It is concluded
      that F5F8D of the proband is caused by a novel compound heterozygous mutation of
      the lman1 gene, which has never been reported.

PMID- 20137145
TI  - [Change of coagulation and fibrinolysis in rabbit model with acute decompression
      sickness and its mechanism].
AB  - This study was purposed to investigate the changes in coagulation and
      fibrinolysis pathways in rabbits suffered from the acute decompression
      sickness(DCS). Model of DCS in rabbits was established. Survival rate and
      symptoms of DCS in animal model was monitored. The prothrombin time (PT),
      activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen
      (Fib), fibrinogen degradation product (FDP) and D-dimers were measured before
      compression and at 0, 3, 24 hours after decompression by latex agglutination
      semiquantitative methods. The changes of plasmin-antiplasmin complex (PAP),
      fibrinopeptide A (FPA), plasminogen activator inhibitor 1 (PAI-1) and
      thrombomodulin (TM) were measured by ELISA at different time points after
      decompression. The results showed that the model of DCS in rabbits was
      successfully established. There was a statistically significant extension in
      APTT, TT, increase of Fib concentration at 15 minutes after decompression, the
      changes were peaked at 3 hours and recovered at 24 hours after decompression. The
      concentration of FDP significantly decreased at 3 hours after decompression. The
      concentration of D-dimers significantly increased at 24 hours after decompression
      in rabbits model with DCS. FPA concentration was significantly increased at 15
      minutes and recovered at 24 hours after decompression. PAP concentration was
      increased after decompression, but had no significant changes. PAI-1 could not be
      detected. TM significantly increased after decompression. It is concluded that
      the acute DCS significantly impacts on blood coagulation system in rabbit model.
      It is shown that hypocoagulation occurred at initial time and hyperfibrinolysis
      subsequently, which varied with time. The damage of blood vessel endothelium may
      be one of the causes of these variations.

PMID- 20137146
TI  - [Relationship between apoptosis and CD30 expression of activated T-lymphocyte in
      patients with chronic idiopathic thrombocytopenic purpura].
AB  - This study was aimed to detect the CD3(+) count, ratio of CD3(+)/CD30(+) T
      lymphocytes, the apoptosis rate of activated T-lymphocytes in peripheral blood
      mononuclear cells and the circulating platelet counts in patients with chronic
      idiopathic thrombocytopenic purpura (ITP), and to investigate the relationship
      between them. 40 cases of chronic ITP patients were taken as the research group
      and 24 healthy persons were served as the control group. The CD3 count, ratio of
      CD3/CD30 T-lymphocytes and the apoptosis rate of activated T-lymphocytes were
      detected by flow cytometry, the platelet count was measured at the same time. The
      difference between 2 groups and correlation of the activated T lymphocyte CD30
      expression rate with apoptotic rate and platelet count in patients were analysed.
      The results showed that there was no significant difference in the count of
      peripheral blood CD3(+) cell between the research group and the control group (p
      > 0.05). The expression of CD30 on activated T-lymphocytes in ITP group was
      obviously higher than that in control group (p < 0.01). The apoptosis rate of
      activated T-lymphocyte in ITP group was remarkably lower than that in control
      group (p < 0.01). The expression of CD30 on activated T-lymphocyte exhibited a
      negative correlation with the apoptosis rate (r = -0.786, p < 0.01). The
      apoptosis rate of activated T-lymphocyte was positively correlated with the
      platelet count of peripheral blood (r = 0.680, p < 0.01). It is concluded that
      the high expression of CD30 on activated T-lymphocytes in patients with chronic
      ITP results in the inhibition of apoptosis, which leads to immune disorder and
      thrombocytopenia.

PMID- 20137147
TI  - [Detection of bcr/abl fusion gene and its derivative chromosome 9 deletions in
      CML by using home-made bcr/abl extra-signal probe].
AB  - This study was aimed to verify the efficacy of home-made LSI bcr/abl ES probe for
      detection of bcr/abl fusion gene and derivative chromosome 9 deletions in chronic
      myeloid leukemia (CML). Fluorescence in situ hybridization (FISH) was carried out
      with dual color bcr/abl extra signal (ES) probe in 97 cases of CML based on
      morphology and cytogenetic karyotype and 129 cases of non-hematological
      malignancies/non-myeloproliferative diseases with normal cytogenetic karyotype.
      For the patients with signals of 1R1G1F indicating der(9) deletions, FISH were
      done using ASS DNA probe. The results showed that 91 cases with standard t(9;22)
      and 6 cases with variant translocation of t(9;22) were detected by conventional G
      banding technique. All of the 97 patients displayed bcr/abl fusion gene by ES
      FISH, including 16 cases with signal patterns of 1R1G1F showing der(9) deletions.
      Among the 16 cases with der(9) deletions, 13 cases were detected to have
      deletions of ASS gene. Meanwhile, none of the 129 cases of negative control
      showed bcr/abl fusion gene by ES-FISH. It is concluded that home-made LSI bcr/abl
      ES probe is effective to identify the bcr/abl fusion gene and der(9) deletions in
      CML, and the ES-FISH results are consistent with conventional cytogenetic
      karyotype.

PMID- 20137148
TI  - [Application of interphase FISH on cell smears in detection of hematological
      diseases].
AB  - The study was aimed to investigate the application value of interphase
      fluorescence in situ hybridization (FISH) on cell smears in hematological
      diseases. Both interphase FISH on peripheral blood smears and bone marrow smears
      treated by methanol/acetic acid, and routine interphase FISH of bone marrow cells
      dropped on slides were done at the same time, in order to detect Ph chromosome by
      BCR/ABL dual color, dual fusion probe in 20 patients with chronic myelogenous
      leukemia or acute lymphoblastic leukemia which had been proven to display Ph
      chromosome positive. The results indicated that as compared with routine
      interphase FISH, the interphase FISH on cell smears could also offer reliable
      result. It is concluded that interphase FISH on cell smears is a kind of reliable
      and time-saving technique, which is also suitable for retrospective research and
      worthy to further apply in clinic.

PMID- 20137149
TI  - [Analysis of efficacy and related factors in 85 chronic myeloid leukemia patients
      treated with imatinib mesylate].
AB  - The objective of this study was to evaluate the efficacy of Imatinib on patients
      with chronic myeloid leukemia (CML) in chronic phase and to analyze its
      influencing factors. 85 patients received Imatinib mesylate at a dose of 300-600
      mg orally per day, and were evaluated for hematologic, cytogenetic, and molecular
      responses. The results showed that the median follow-up was 21 (range 9 - 78)
      months. Cumulative complete hematological remission (CHR) rate was 100%, major
      cytogenetic remission (MCyR) rate was 80%, complete cytogenetic remission (CCyR)
      rate was 67.1% and complete molecular remission (CMoR) rate was 36.4%. The median
      time to complete hematological remission (CHR) was 1 (range 1 - 3) month, to
      complete cytogenetic remission (CCyR) was 6 (range 1 - 24) months. The estimated
      overall survival rates for patients who received Imatinib for 1, 2, 3 years were
      (98.7 +/- 1.3)%, (96.5 +/- 2.5)% and (90.1 +/- 6.6)% respectively. The estimated
      progression-free survival rates at 1, 2, 3 years were (97.6 +/- 1.6)%, (96.1 +/-
      2.2)% and (90.0 +/- 1.4)% respectively. The CHR, MCyR and CCyR between low risk,
      intermediate risk and high risk groups according to the Sokal scoring system and
      between primarily treated and retreated groups all had no difference. The overall
      survival of patients who achieved MCyR or CCyR was better than that in patients
      only achieved hematologic remission (p = 0.026), but there was no significant
      difference in progression-free survival between them. Univariate analysis for
      efficacy of Imatinib mesylate revealed that WBC count < 100 x 10(9)/L (p =
      0.024), Hb level > or = 130 g/L (p = 0.036), and peripheral basophil count < or =
      0.05 (p = 0.024) before therapy were independent favourable factors for achieving
      MCyR or CCyR. It is concluded that the patients with CML in chronic phase treated
      with Imatinib can achieve the best hematologic remission and higher cytogenetic
      remission, it should be considered that the imatinib is a drug of the first-line
      therapy for untreated and treated patients with CML.

PMID- 20137150
TI  - [Efficiency of GHA priming therapy on patients with acute monocytic leukemia and
      its mechanism].
AB  - The aim of this study was to explore the clinical efficiency and side effects of
      GHA-priming therapy on patients with acute monocytic leukemia, and to analyze its
      mechanism. 37 patients with refractory, relapse, hypocellular acute monocytic
      leukemia and elderly patients with AML-M(5) were treated with GHA-priming therapy
      (G-CSF, homoharringtonine and low dosage of cytarabine). Clinical efficiency,
      side effects, and therapy-relevant mortality were observed. By using U937 cell
      line as in vitro model, effect of G-CSF on cell cycle was determined by propidium
      iodide staining method. The inhibition rate, apoptosis rate of U937 cell line
      treated with various combination of G-CSF, homoharringtonine and cytarabine were
      detected by flow cytometry. The expression of MLAA34 on U937 before or after
      treating with chemotherapy was analyzed by immunohistochemical method. The
      results showed that in all the 37 patients, the total remission rate was 62.2%
      [complete remission rate was 45.95% (17/37) and partial remission rate was 16.2%
      (6/37)]. The incidence of granulocyte deficiency was 18.92% (2/37) with median
      time of 4 days. The severe infection occurred in 2 cases. No severe bleeding, no
      mild digestive effect occurred. Other non-hematological toxicities were low in
      vitro when incubated with G-CSF for 24 hours, the S-phase cells obviously
      increased. The inhibition rate, apoptosis rate and expression of MLAA34 of U937
      cells treated by GHA significantly decreased as compared with cells treated with
      HA. It is concluded that the GHA priming therapy can be used to treat patients
      with refractory, relapse, senile and hypocellular acute monocytic leukemia with
      satisfied response rate and low hematological and non-hematological toxicities. G
      CSF can enhance cytotoxicity of drugs such as Ara-C and HHT by promoting G(0)
      phase cells into the reproductive cycle. GHA and HA therapy can inhibit cell
      proliferation, induce apoptosis, and the former has a more significant function.
      GHA priming therapy can down regulate the expression of MLAA 34. MLAA-34 is a
      novel anti-apoptotic factor of acute monocytic leukemia.

PMID- 20137151
TI  - [Therapy of relapsed or refractory non-Hodgkin's lymphoma by antigen specific
      dendritic cells-activated lymphocytes].
AB  - This study was aimed to investigate the killing activity of cytokine-induced
      killer (CIK) cells after being incubated with autologous tumor cell lysate-pulsed
      dendritic cells (DC) and to evaluate the clinical efficacy and side effect of
      autologous tumor cell lysate-loaded DC in combination with CIK on relapsed or
      refractory non-Hodgkin's lymphoma (NHL). Peripheral blood mononuclear cells
      (PBMNC) were isolated from 9 patients with NHL, and cultured with granulocyte
      macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to produce
      DC. The DC were pulsed with autologous tumor cell lysate. T lymphocytes from
      PBMNC were cultured with interferon-gamma (IFN-gamma), IL-2, CD3-moAb, and IL
      1alpha to prepare CIK. After receiving the immunotherapy of DC and CIK,
      immunologic and clinical responses were evaluated. The results showed that the
      AgNOR, CD3(+)CD8(+) and CD3(+)CD56(+) ratio were markedly improved after the
      immunotherapy (p < 0.01); IFN-gamma and IL-12 levels in supernatant of DC-CIK
      group were higher than that in CIK group (p < 0.01); Tumor size were
      significantly decreased after the immunotherapy (p < 0.05). Except transient
      fever and chill, no remarkable adverse event happened during or after the
      treatment. It is concluded that the autologous tumor cell lysate-pulsed DC in
      combination with CIK show ability to specifically kill the lymphoma cells,
      obviously increases the IS value of Ag-NOR in peripheral lymphocytes, secretes
      cytokines higher than CIK cells alone. This combination displays the short-term
      satisfied efficacy on NHL through inducing specific antitumor immunity, and can
      be used as an effective adjuvant measure for the routine therapy of NHL.

PMID- 20137152
TI  - [In vitro activity of human bone marrow cells after cryopreservation in liquid
      nitrogen for 21 - 25 years].
AB  - The aim of this study was to investigate the best method to preserve human bone
      marrow cells and the effectiveness of long term cryopreservation at -80 degrees
      C. The human bone marrow cells in 20 samples were firstly frozen by a programmed
      freezer or -80 degrees C refrigerator, and then were preserved in liquid nitrogen
      with DMSO-AuP (10% dimethylsulfonamide, 10% autologous plasma) or DMSO-HES-HuA
      (5% dimethylsulfonamide, 6% hydroxyethyl starch, 4% human serum albumin) as
      cryoprotectant for 21 to 25 years. They were thawed in 38 degrees C. The cell
      sample frozen in -80 degrees C refrigerator was frozen at a low frozen speed of 1
      degrees C/min which was the same as the programmed freezer before -30 degrees C.
      Before detection the bone marrow cells were taken from liquid nitrogen and were
      thawed in 38 degrees C, then the suspension of bone marrow cells was prepared for
      detection. The cell morphology and recovery rate of erythrocytes, nucleocytes and
      platelets; the recovery rate of hematopoietic stem progenitors cells, as well as
      mesenchymal stem cells were determined. The results showed that the protective
      effectiveness of DMSO-HES-HuA was better than DMSO-AuP. The mature erythrocytes
      were destroyed lightly [(3.5 +/- 1.5)% versus (12.6 +/- 4.8)%], the hemolysis
      rate was lower [(3.3 +/- 1.6)% versus (23.1 +/- 5.1)%]. Osmotic fragility of
      erythrocytes in the former was not changed, but was dropped in the latter. The
      recovery rates of red cell, platelet, granulocyte-macrophage colony forming units
      and long term culture-initiating cells were higher in the former than that in the
      latter [(96.1 +/- 1.8)%, (70.0 +/- 9.5)%, (49.2 +/- 10.9)%, (54.2 +/- 13.8)%
      versus (76.3 +/- 5.6)%, (52.7 +/- 8.1)%, (43.5 +/- 12.3)%, (47.2 +/- 13.6)%
      respectively]. With each kind of cryoprotectant or frozen method, the frozen MSC
      could keep the original growth properties. With the same cryoprotectant and
      different frozen method, the cryopreservative effectiveness was not different.
      The influence of the cryoprotectant prescriptions and the frozen methods on the
      cryopreservative effectiveness was little. It is concluded that the human bone
      marrow cells with DMSO-AuP or DMSO-HES-HuA as cryoprotectant, frozen by a
      programmed freezer or -80 degrees C refrigerator, could be then preserved in
      liquid nitrogen for long time. When the preserving time was as long as 21 to 25
      years, the morphology, the recovery rate and the activity of various kinds of
      cells were still good. The method of freezing by -80 degrees C refrigerator with
      5% DMSO-6% HES-4% HuA and preserving in liquid nitrogen would be convenient,
      cheap and easily-manipulated for preservation of the human bone marrow cells.

PMID- 20137153
TI  - [Progress of research on leukemia stem/progenitor cell targeting therapy].
AB  - At present, most patients with hematological malignancies are treated with
      conventional chemotherapy, but the relapse frequently occurs in these patients.
      It is increasingly recognized that the cause of relapse resides in a small
      portion of the leukemia stem/progenitor cell population which has self-renewal
      and multilineage differentiation potential. As traditional chemotherapeutic drugs
      only kill the majority of differentiated tumor cells and hardly affect the tumor
      stem/progenitor cell, that is why most of the chemotherapies did not achieve good
      results. In order to completely eradicate hematological malignancies, intrinsic
      properties of stem/progenitor cells must be studied and only the therapy
      targeting this population could make tumor curable. Targeting the surface markers
      which distinguish the tumor stem/progenitor cells from normal stem/progenitor
      cells, inducing the tumor stem/progenitor cell differentiation, disrupting the
      signal pathways and niche which regulate the tumor stem/progenitor cell self
      renewal are all probable strategies. This review summarizes recent progress of
      research on leukemia stem/progenitor cell targeting therapy development.

PMID- 20137154
TI  - [Leptin and its receptor in acute myeloid leukemia].
AB  - Leptin, the product of obese gene, is a secreting protein that exerts multiple
      biological functions by binding to its receptor. Leptin regulates nutrient intake
      and metabolism, and is secreted from adipocytes, which occupy most of the bone
      marrow cavity and constitute the microenvironment. Leptin not only plays an
      important role in the control of the proliferation and differentiation of normal
      primitive hematopoietic cells, but it also stimulates the growth and viability of
      leukemic cells. Leukemic cells of some patients with acute myeloid leukemia
      (AML), acute lymphoblastic leukemia, and chronic myeloid leukemia also express
      the leptin receptor. Furthermore, leptin also stimulates leukemic cell growth in
      vivo by promoting angiogenesis. These findings suggest the possibility that
      leptin and its receptor play roles in the pathophysiology of leukemia, and
      blockage of leptin binding to its receptor might have potential therapeutic
      benefits in the treatment of certain leukemias. This review discusses the
      biological characteristics of leptin and its receptor, the relation of leptin and
      its receptor with normal hematopoiesis, the relation of leptin and its receptor
      with AML and so on.

PMID- 20137155
TI  - [Novel progress on treatment of acute graft-versus-host disease].
AB  - Acute graft-versus-host disease (aGVHD) is a common complication after allogeneic
      hematopoietic stem-cell transplantation. Despite improvements in understanding of
      transplant immunology, aGVHD remains to be a major cause of mortality for
      patients after allogeneic hematopoietic stem-cell transplantation. While systemic
      corticosteroid is standard primary therapy for aGVHD, there is no established
      standard treatment for patients in the steroid-refractory setting. Over the past
      decade, monoclonal antibodies, biologic engineering products, and
      chemotherapeutics with immunomodulatory effects are being used as novel therapies
      in this disease. Many of these agents, such as mycophenolate mofetil, anti-tumor
      necrosis factor antibodies, and anti-interleukin-2Ralpha-chain antibodies, have
      demonstrated promising activity in steroid-refractory aGVHD. But long-term
      survival remains poor due to a high incidence of infections. The key to improving
      aGVHD outcomes may, in fact, rest upon successful initial therapy, and timely
      taper corticosteroids to promote immune reconstitution. Clinical trials combining
      these newer agents with systemic corticosteroids as initial treatment are under
      way. In this article some new treatments for acute aGVHD are recommend and
      summarized.

PMID- 20137156
TI  - [Research advance on the pathogenesis of T-ALL induced by notch 1 activating
      mutations].
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is the hematological malignancy of
      bone marrow characterized by the rapid proliferation and subsequent accumulation
      of immature T lymphocyte and mainly occurs in children and adolescents. In 1991,
      a kind of activating mutation of Notch 1 was found in a subset of T-ALL with
      chromosomal translocation t(7;9) for the first time. During the past 20 years
      since then, understanding of the relationship between Notch 1 activating mutation
      and T-ALL has been deepened and widened. This review briefly discusses the four
      main subtypes of Notch 1 activating mutations, also focuses on how these
      mutations change the normal signaling pathways and genes expression during their
      participation in the pathogenesis of T-ALL, and how these insights will promote
      the development of newly targeting therapies for patients with this aggressive
      form of leukemia.

PMID- 20137157
TI  - [M-FISH technique in diagnosis and prognostic analysis for acute leukemia with
      complex chromosomal aberrations].
AB  - The M-FISH includes multi-colour FISH and multiplex FISH, it represents one of
      the most significant developments in molecular cytogenetics of the past decade.
      This technique was originally designed to generate 24 colour karyotyping in
      human's 23 pair chromosome, now the technique has many variations and has been
      used in different fields. In leukaemia cytogenetics, the M-FISH now is used in
      detection for AL patients with following chromosome abnormality: (1) harbouring
      minimal chromosome translocation is respected; (2) chromosome translocation with
      complex abnormal karyotypes exists in patients with leukemia which are difficulty
      detected by using conventional method. The final results detected by M-FISH have
      guide significance for diagnosis, therapy and prognosis of AL patients. In this
      article the technical basis with commonly used probe for M-FISH, application of M
      FISH in diagnosis, evaluation of therapeutic efficacy and prognostic analysis of
      AL patients are summarised.

PMID- 20137158
TI  - [Correlation between single nucleotide polymorphisms and hematological
      malignancies].
AB  - Single nucleotide polymorphisms (SNPs) are the 3rd generation of molecular
      genetic markers of human populations.SNPs determine the functional units of genes
      and the inherent characteristics of genetic variation, and reflect the individual
      phenotype, disease susceptibility and differences of response to drug and
      environmental factors. Hematological malignancy is a multi-gene genetic diseases,
      and involve in the role of multigenic susceptible genes. This review intends to
      introduce the single nucleotide polymorphisms and their relevant progress of
      research on hematologic malignancies, including the SNP of carcinogen
      metabolizing enzymes genes, the SNP of DNA repair genes, the SNP of oncogenes and
      anti-oncogene genes, the SNP of drug-metabolizing enzyme genes and so on.

PMID- 20137159
TI  - [Voltage-dependent anion channel and hematological malignancies].
AB  - Voltage-dependent anion channel(VDAC)is mainly located on the outer mitochondrial
      membrane. High-resolution atomic force microscopy topography shows an eye-shaped
      VDAC with 3.8 nm x 2.7 nm pore dimensions. New work suggests pore formation by
      the assembly of homo-oligomers and supramolecule of VDAC or hetero oligomers
      composed of VDAC and pro-apoptotic proteins, such as Bax. The oligomeric VDAC
      pore allows for release of cytochrome C. Thus, VDAC plays a central role in the
      cell life and apoptosis. It has been shown that the hexokinase (HK)-VDAC1
      interaction is critical for preventing induction of apoptosis in tumor cells.
      VDACs are expressed more highly in cancer cells than normal cells, thus can be
      used as the target in chemotherapy for cancer. VDAC is also involved in
      pathogenesis of hematological malignancies such as myeloma and chronic
      lymphocytic leukemia. Following identification of sequence and structure of VDAC,
      studies have focused on VDAC as important pharmacological target for new
      anticancer therapy. To induce apoptosis, agents directly interact with VDAC or
      detach HK from VDAC to disrupt the anti-apoptosis activity of VDAC-HK
      interaction, such as methyl jasmonate (MJ) and VDAC1-based peptides. In this
      review, the function, modulation, structure and location of the VDAC, progress of
      its researches in hematological malignancies and potential as targets of anti
      cancer drugs are summarized.

PMID- 20137160
TI  - [Research advance on hemophagocytic lymphohistiocytosis].
AB  - Hemophagocytic lymphohistiocytosis (HLH) is named as hemophagocytic syndrome
      (HPS) and is a complicated disease with reactive hyperplasia of
      mononuclear/macrophagocytic system. This disease characterised by release of
      massive cytokines and severe functional destruction of visceral organs, which
      results from immune function disturbance causing by various pathogenic factors.
      The cardinal clinical symptoms of HLH are prolonged fever, hepatosplenomegaly,
      cytopenia, elevated ferritin and triglycerides, low fibrinogen, symptom in nerve
      system and so on. Nevertheless, impaired function of natural killer cells and
      cytotoxic T-cell is characteristic for HLH. HLH has of two different types that
      may be difficult to distinguish from one another: a primary and a secondary form.
      The combined immunochemotherapy of dexamethasone, etoposide and cyclosporin A and
      hematopoietic stem cell transplantation are considered as the effective therapies
      for HLH. In this article, the recent advance in research on the etiological
      factors, pathogenesis, clinical manifestations, laboratory examination, diagnosis
      as well as recommended therapy of HLH were reviewed.

PMID- 20137161
TI  - [Research advance on transfusion-related immunomodulation].
AB  - As allogeneic blood transfusion plays a role in clinical treatment effects, it
      also produces a number of immune-related side effects, such as the increased rate
      of postoperative infection, the rising relapse rate of malignant resection and so
      on. All those factors, such as CD200 surface molecule of allogeneic mononuclear
      cells, interleukin, sHLA and sFasL which are detached from the leukocyte surface
      during the period of storage, and serum bioactive molecules related to a certain
      degree with the occurrence of transfusion-related immunomodulation (TRIM). The
      clinical controlled trials, laboratory researches and animal models demonstrated
      that cloning deletion, induction of anergy and immune suppression are the three
      major mechanisms of TRIM. In this article, the research advances on mechanism of
      TRIM and the mediators inducing TRIM are reviewed.

PMID- 20137162
TI  - [Research advance on transferrin receptor in hematological malignant tumor
      treatment].
AB  - Iron is one of the necessary elements for cell growth, proliferation and
      functional activities. Iron uptake of the vast majority cells, including tumor
      cells, is primarily mediated by transferrin receptor (TfR). Studies showed that
      transferrin receptor expressed on tumor cell surface at a high level, thus can be
      used in the treatment for malignant tumor combined with many kinds of materials.
      In this article, recent progress of study on transferrin receptor used in
      treating hematological malignant tumor are reviewed from aspects of transferrin
      receptor combined with drugs including artemisinin, doxorubicin, gambogic acid
      and so on, genes, antibodies, polyethylene glycol and nanoparticles.

PMID- 20137163
TI  - The effects of cognitive activity and perceptual details on speech source
      monitoring.
AB  - Our purpose in this study was to investigate the effects of cognitive operations
      and perceptual details on speech source monitoring. In Phase 1, correctly spelled
      words and anagrams were presented in Expt 1. Words were read aloud by
      participants, by a same-sex voice, or by an opposite-sex voice. Immediately after
      Phase 1, in Phase 2, participants were asked whether each word had been read
      aloud by the participants themselves, by a same-sex voice, or by an opposite-sex
      voice. Source discrimination between own speech and that produced by a same-sex
      voice was poorer than between own speech and an opposite-sex voice. In addition,
      misattribution of the speech of another to one's self increased as the level of
      cognitive effort required for the task increased. In Expt 2, misattributions to
      same-sex voice were assigned 'know' responses more frequently and misattributions
      to one's self were assigned 'remember' responses more frequently. These results
      suggest that qualitative characteristics such as perceptual detail and cognitive
      operations are differentially influencing misattributions to the self and those
      to same-sex voices.

PMID- 20137263
TI  - [Imaging features of pediatric Gaucher disease].

PMID- 20137264
TI  - [Prevalence and associated risk factors of hyperuricemia in rural hypertensive
      patients].
AB  - OBJECTIVE: To investigate the prevalence of hyperuricemia and its associated risk
      factors in treated and untreated hypertensive patients in Chinese rural area.
      METHODS: This cross-section study was performed in 5235 hypertensive patients
      aged 40 - 75 years old at Xinyang, Henan by using a multistage cluster sampling
      method. All patients underwent an investigation composed of a standardized
      questionnaire, physical and biochemical examination. Hyperuricemia was defined as
      serum uric acid levels > or = 420 micromol/L in men or > or = 360 micromol/L in
      women. RESULTS: The overall prevalence of hyperuricemia was 14.1%, and it was
      higher in men than in women (21.5% vs 10.2%, P < 0.01). With an increase of body
      mass index (BMI), the prevalence of hyperuricemia and serum uric acid level
      increased significantly in both sexes [BMI < 25, > or = 30: 14.4%, 30.4%, (328 +/
      83) micromol/L, (383 +/- 86) micromol/L in males; and 7.2%, 17.0%, (251 +/- 70)
      micromol/L, (293 +/- 75) micromol/L in females, respectively, all P < 0.01]. So
      did that with increase of age only in female patients (40 - 49 years vs > or = 70
      years: 5.8% - 18.0%, respectively, P < 0.01). Antihypertensive treatment, lipid
      disorder, smoking and alcohol consumption also significantly increased the
      incidence of hyperuricemia and the serum uric acid level (all P < 0.01). However,
      no significant differences were found among patients with I, II, and III blood
      pressure levels (all P > 0.05). After adjustment for age and other conventional
      risk factors by using multiple logistic regression analysis, hyperuricemia was
      significantly associated with BMI, alcohol consumption and diuretics in males as
      well as BMI, lipid disorder, age, smoking, and antihypertensive treatment in
      females. CONCLUSIONS: Hyperuricemia is relatively less common in rural
      hypertensive patients. The associated risk factors of hyperuricemia and elevated
      serum uric acids include sex, age, BMI, antihypertensive medicines, lipid
      disorder, smoking and alcohol consumption. The effect of these factors is
      different between sexes.

PMID- 20137265
TI  - [Comparison of sub-health status between Tibetan people and Han people].
AB  - OBJECTIVE: To compare the prevalence of sub-health status between Han people and
      Tibetan people. METHODS: Subjects were selected with two-stage clustering
      sampling method in Sichuan Province. The sub-health rating scale developed by
      Chen Qing-shan, et al was employed to assess the sub-health status of subjects.
      The prevalence of sub-health status was compared between two groups with logistic
      regression model and binomial regression model after adjusting some confounding
      factors, such as age, gender, marital status, hypertension, occupation, exercise,
      overweight, smoking and drinking status. RESULTS: Prevalence rates of sub-health
      status were 52.3% (3611/6911) and 57.9% (1034/1787) in Han and Tibetan people
      respectively. Logistic regression analyses results showed that the risk of sub
      health in Tibetan people was 1.2840 times that in Han people (95%CI 1.1460
      1.4390). Negative binomial model indicated that the number of sub-health symptoms
      was greater in Tibetan people and the risk was 1.2908 (95% CI 1.1820-1.4096).
      Prevalence rates of all sub-health dimensions were higher in Tibetan people.
      CONCLUSIONS: Tibetan people dwelling in high-altitude areas are more susceptible
      to suffer from sub-health status. The medical researchers should pay more
      attention to this problem.

PMID- 20137266
TI  - [Polymorphisms of drug-metabolizing enzymes genes in a Han Chinese population].
AB  - OBJECTIVE: To survey the frequencies and characteristics of polymorphism of seven
      genes coding drug-metabolizing enzymes in a Han Chinese population. METHODS:
      Genomic DNA was extracted from peripheral blood in 1382 unrelated Han Chinese
      volunteers. Genotypes of CYP450, NQO1, MPO, MTHFR, NAT2, TPMT*3B(G460A) and
      TPMT*3C(A719G) were analyzed by PCR-RFLP. GSTM1 and GSTT1 genotypes were detected
      by multiple PCR and TPMT*2(G238C) genotypes by allele-specific PCR. RESULTS: The
      allele frequencies of wild-type, heterozygosity and homozygosity were 99.8%, 0.2%
      and 0 in CYP3A4*1B genotypes, 8.4%, 34.3% and 57.3% in CYP3A5*3 genotypes, 28.7%,
      49.7% and 21.6% in NQO1(C609T) genotypes, 75.0%, 23.2% and 1.8% in MPO(G463A)
      genotypes, 25.9%, 44.9% and 29.2% in MTHFR(C677T) genotypes, 67.3%, 30.4% and
      2.3% in MTHFR(A1298C) genotypes, and 96.8% 3.2% and 0 in TPMT*3C(A719G)
      genotypes, respectively. The frequencies of present and null genotypes were 36.1%
      and 63.9% in GSTM1, 54.4% and 45.6% in GSTT1 respectively. The frequencies of
      NAT2*4/*4, *4/*5, *4/*6, *4/*7, *5/*5, *5/*6, *5/*7, *6/*6, *6/*7 and *7/*7
      genotypes were 34.5%, 4.3%, 24.3%, 18.2%, 0.1%, 1.8%, 1.5%, 5.0%, 7.6% and 2.6%
      respectively. The frequencies of specific NAT2 alleles were 57.9%, 3.9%, 21.8%
      and 16.3% for NAT2*4, *5, *6 and *7 respectively. The frequencies of
      genophenotypes were 81.4% and 18.6% in NAT2 fast acetylator and low acetylator
      respectively. The allele frequency of wild type were 100% in both TPMT*2(G238C)
      genotypes and TPMT*3B(G460A). The variant alleles of TPMT*2(G238C) and
      TPMT*3B(G460A) were not found in 1382 Han Chinese subjects. CONCLUSION:
      Significant differences in the distributions and frequencies in genetic
      polymorphisms of drug-metabolizing enzymes are identified between Han Chinese
      population and Caucasians, as well between Han Chinese population and Melanoderma
      while only some heterogeneity has been observed between Han Chinese population
      and other Xanthoderms in Asia.

PMID- 20137267
TI  - [Epidemiological study on status of Helicobacter pylori in children and teenagers
      in Wuwei city, Gansu province].
AB  - OBJECTIVE: To investigate the prevalence of Helicobacter pylori (Hp) infection
      among children aged 3 to 18 years old of Wuwei city, Gansu province. METHODS: The
      study was based upon a personal questionnaire and a determination of Hp antigen
      using the Hp stool antigen test (HpSA) method. A total of 938 subjects and 96
      families were selected in Wuwei city. Eighty children and teenagers with a
      definite positive Hp stool antigen test were examined by serum Western blotting
      method. RESULTS: The prevalence of Hp was 72.3% (678/938) with no age difference.
      Prevalence of Hp infection was correlated with type of dwelling, occupation of
      parents, drinking water source, kindergarten attendance, consumption of raw
      vegetables, a poor oral hygiene and breast feeding etc. According to the
      multivariate analysis, drinking water source, kindergarten attendance and
      consumption of raw vegetables were most strongly associated with prevalence of Hp
      in children and adolescents. The infection rate of parents whose children were
      infected with Hp was higher than that of those whose children were not infected
      [82.3% (121/147) vs 47.4% (18/38), chi(2) = 19.736, P < 0.05]. The antibody
      responses of 57 samples (71.3%) from 80 children were of type I Hp and 23 samples
      (28.7%) type II. CONCLUSIONS: Hp infective rate is high in Wuwei city. The data
      support maternal-child and sibling-sibling transmission as the primary
      transmission routes of Hp. The results of serological analysis confirm that the
      majority of Wuwei Hp infection is of type I.

PMID- 20137268
TI  - [Effect of continuous positive airway pressure upon 24 h changes of blood glucose
      level in patients with obstructive sleep apnea hypopnea syndrome and type 2
      diabetes].
AB  - OBJECTIVE: To assess the effect of short-term continuous positive airway pressure
      (CPAP) upon 24 h glucose control via a continuous glucose monitoring system
      (CGMS) in patients with obstructive sleep apnea hypopnea syndrome and type 2
      diabetes (OWD). METHODS: Eleven cases of hospitalized OWD with age 43 - 70 (56 +/
      10) years old, body mass index 22.3 - 38.3 (28.5 +/- 5.5) kg/m(2) and apnea
      hypopnea index (AHI) 12 - 68 (45 +/- 23) times/h was recruited. CGMS was applied
      2 days before and 4 days during CPAP treatment. The 24 h, treatment hours (6 h,
      0:00-6:00) and non- treatment hours (18 h) glucose level and glucose variability
      were analyzed. Insulin resistance was assessed with fasting plasma blood glucose
      (FBG), plasma insulin (FINS) and homeostatic model assessment of insulin
      resistance index (HOMA-IR). RESULTS: Short-term CPAP treatment corrected sleep
      disordered breathing, and induced significant decreases of 24 h and treatment
      hours blood glucose level [(7.97 +/- 1.31) vs (7.52 +/- 0.94) mmol/L, (7.24 +/-
      1.51) vs (6.77 +/- 1.65) mmol/L, both P < 0.05). Glucose variability of 24 h and
      treatment hours and non-treatment hours significantly decreased after CPAP
      treatment (1.22 +/- 0.34 vs 0.89 +/- 0.28, 0.43 +/- 0.24 vs 0.31 +/- 0.18, 1.23
      +/- 0.89 vs 0.49 +/- 0.26, all P < 0.05). Short-term treatment also induced
      increase of insulin sensitivity, as indicated by a significant decrease of HOMA
      IR (3.65 +/- 1.93 vs 2.79 +/- 1.68, P < 0.05). CONCLUSION: Short-term CPAP
      treatment in OWD may have an improving effect not only upon insulin resistance
      but also upon whole-day blood glucose and glucose variability.

PMID- 20137269
TI  - [Association of ENA-78, IP-10 and VEGF gene polymorphism with idiopathic
      pulmonary fibrosis].
AB  - OBJECTIVE: To examine whether there was an association between epithelial
      neutrophil activating peptide 78 (ENA-78), interferon-inducible protein 10 (IP
      10), vascular endothelial growth factor (VEGF) polymorphism and Chinese patients
      with idiopathic pulmonary fibrosis (IPF). METHODS: Polymerase chain reaction
      (PCR) and restriction fragment length polymorphism (RFLP) were performed to
      analyze the gene polymorphisms of ENA-78 (-156G/C), IP-10 (-1596C/T) and VEGF
      (+405G/C) in 60 IPF patients and 60 controls with trauma or bone fracture matched
      in age, gender and smoking status. RESULTS: The distribution of carrying GC + CC
      genotype frequency (20.0%) and C allele frequency (12.7%) for ENA-78 in IPF
      patients was significantly higher than that in healthy controls [6.7% (P = 0.032)
      and 3.3% (P = 0.008), respectively], the relative risk of suffering from IPF of 
      156C allele gene carrier significantly increased (OR = 4.23, 95%CI: 1.35-13.20).
      The distribution of carrying CT + TT genotype frequency (10.0%) and T allele
      frequency (5.8%) for IP-10 in IPF patients was significantly lower than that in
      healthy controls [26.7% (P = 0.018) and 14.2% (P = 0.031), respectively], the
      relative risk of suffering from IPF of -1596T allele gene carrier decreased (OR =
      0.38, 95%CI: 0.15-0.95). No association was found between VEGF (+405G/C)
      polymorphism and IPF. CONCLUSIONS: -156C allele for ENA-78 may be a risk factor
      of IPF and -1596T allele for IP-10 a beneficial factor of IPF. The VEGF (+405G/C)
      gene polymorphism has no effect upon the predisposition to IPF.

PMID- 20137270
TI  - [Preliminary experience with partial tolerance protocol in small bowel
      transplantation].
AB  - OBJECTIVE: To report the preliminary experience of 4 cases of small bowel
      transplantation. METHODS: Thirty microgram of Campath 1H was infused during the
      small bowel transplantation. The patients received 1 gram of Solu-Medrol followed
      by the Campath 1H and another gram of Solu-Medrol before reperfusion. The
      infusion of tacrolimus started just after reperfusion. The route of tacrolimus
      administration was transferred from vein to gut tract gradually, the tacrolimus
      trough levels were aimed at 10-15 microg/L within the first 3 postoperative
      months, 5-10 microg/L at 4-6 months post-operation and taped to 5 microg/L
      thereafter. RESULTS: Two of these 4 cases survived more than one year. The follow
      ups of other 2 patients were 6 and 2 months respectively. Three episodes of IND
      to mild acute rejection verified by pathology through routine ileoscopical biopsy
      were found at 1-3 months post-operation, anther 3 episodes of IND to mild acute
      rejection verified during at 4-6 months post-operation and one episode of
      moderate acute rejection found at 7-12 months post-operation. The patients
      totally recovering after a low-dose steroid or bolus steroid were given
      respectively. The grafted intestine achieved an excellent function. And the
      patients discontinued TPN at 2-3 weeks post-operation respectively and lived on a
      normal oral intake to maintain their nutritional status. CONCLUSIONS: The partial
      tolerance steroid-free protocol of combining Campath 1H induction with a low-dose
      monotherapy of tacrolimus can effectively control the graft rejection in small
      bowel transplantation. And the grafted intestine regains an excellent function.

PMID- 20137271
TI  - [Surgical treatment and prognosis of primary retroperitoneal malignant tumor].
AB  - OBJECTIVE: To investigate the surgical treatment and prognosis of primary
      retroperitoneal malignant tumor. METHODS: A total of 191 patients with primary
      retroperitoneal malignant tumor treated from January 1996 to December 2007 at our
      hospital were retrospectively analyzed. SPSS 13.0 was used to analyze the follow
      up data. RESULTS: The clinical manifestations included abdominal mass [122
      (63.9%)], abdominal pain [77 (40.3%)] and abdominal distension [48 (25.1%)].
      Liposarcoma [75 (39.3%)] was more frequently encountered than other tumors. Among
      these patients, 142 underwent complete resection, 35 palliative resection and 14
      exploratory operation. The median survival time of complete resection, palliative
      resection and exploratory operation were 56, 33 and 11 months respectively. The
      difference was of statistical significance. CONCLUSIONS: Surgical resection is an
      effective therapeutic method for primary retroperitoneal malignant tumor.
      Complete resection prolongs the survival time and it is effective in control of
      recurrent tumors.

PMID- 20137272
TI  - [Recovery characteristic of donor's and receptor's renal function from age over
      55 years living donors donate kidneys].
AB  - OBJECTIVE: To observe and research clinical characteristics and curative effect
      and safety of renal transplantation from living elderly donors donating kidneys.
      METHODS: Retrospective study on the 19 living kidney donors who were over 55
      years old and on the renal transplantation operations completed by our center for
      the past few years. Among the 19 donors, with an average age of 58 years old.
      Their mean creatinine clearance was 81.7 +/- 2.2 ml/min. Among the 19 acceptors,
      with an average age of 34 years old. All kidney before the open circulation
      transplant performed routine 0 point puncture and histological examination.
      RESULTS: All donors smoothly spent their perioperative period without any
      surgical complications. All the donors keep their blood Cr in a normal range one
      week after the operation. There was no significant difference between
      posttransplantation one week and six month and one year in blood Cr and Ccr.
      Blood pressure and blood sugar didn't not have significant changes, urine
      protein(-). All receptors' renal functions recovered in early stages without DGF.
      7 receptors who had Ccr lower than 80 ml/min had their blood Cr decreased slowly.
      Among the 19 kidneys donated, 3 donors' glomerulosclerosises were higher than 10
      percent. CONCLUSIONS: The kidney source shortage is the main factor that
      restricts the development of the renal transplantation currently, undoubtedly,
      the application of elderly donors will expand the kidney source and save more
      uremic patients. Renal transplantation is safe and feasible with the help of
      living elderly donors.

PMID- 20137273
TI  - [Therapeutic options and prognosis of multifocal gastric carcinomas].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics, therapeutic
      principles and prognosis of multifocal gastric carcinomas. METHODS: The data of
      22 patients with multifocal gastric carcinomas surgically treated at our hospital
      from January 1999 to December 2007 were reviewed retrospectively. RESULTS: The
      multifocal gastric carcinomas occurred frequently in the elderly men; the
      percentage of early stage gastric carcinoma was 28.9%. Eighteen patients received
      radical resection while 4 patients palliative resection. The 1, 3 and 5-year
      survival rates were 80.9%, 52.4% and 28.6% respectively. CONCLUSIONS: A thorough
      gastric examination should be made before and during resection so as to avoid a
      missing diagnosis. The postoperative survival in patients with multifocal gastric
      carcinomas is similar to those with a solitary lesion.

PMID- 20137274
TI  - [Construction and efficacy study of a novel 10-23 deoxyribozyme expression
      vector].
AB  - OBJECTIVE: To construct a novel 10-23 deoxyribozyme (10-23DZ) expression vector,
      identify the intracellular production of specific 10-23DZ and its inhibitory
      effect upon the expression of TACO gene in macrophage. METHODS: An
      oligonucleotide containing the primer binding sequence of mouse Moloney leukemia
      viral reverse transcriptase (MLV-RT), a multiple cloning site (MCS) and a stem
      loop structure for termination of reverse transcription was designed and inserted
      into one MCS of plasmid pBUDCE4.1, downstream of the cytomegalovirus promoter
      (P(CMV)). The gene fragment encoding MLV-RT was inserted into another MCS of
      pBUDCE4.1, downstream of elongation factor 1alpha promoter (P(EF-1alpha)). The
      resulting plasmid was named pSDE01. Then pSDE01 was transfected into RAW264.7
      cell and the expression of MLV-RT and the reverse transcriptase activity of
      expression product was identified by RT-PCR. To identify the cellular expression
      of 10-23DZ by pSDE01, a 10-23DZ targeting the TACO mRNA of macrophage was
      designed according to the predicted secondary structure of TACO mRNA. The
      expression sequence of designed 10-23DZ, DZ1, was synthesized and inserted into
      the MCS of ODN-PSL in pSDE01. The resulting plasmid, pSDE01-DZ1, was transfected
      into RAW264.7 cell and the expression of DZ1 was identified by PCR and dot-blot
      respectively. At 48 h after transfection of pSDE01 into RAW264.7 cells, total RNA
      and proteins were extracted and the TACO mRNA and protein expression level was
      assayed by RT-PCR and Western blotting respectively. RESULTS: Restrictive
      analysis and sequencing data showed that the 10-23DZ expression vector, pSDE01,
      was successfully constructed and could express MLV-RT with reverse transcriptase
      activity in cell. When transfected into RAW264.7 cells, pSDE01-DZ1 expressed DZ1
      effectively and inhibited the expression of TACO gene. And TACO mRNA decreased by
      77.7% (0.193 +/- 0.008 vs 0.864 +/- 0.005, P < 0.05) and TACO protein decreased
      by 73.3% (0.114 +/- 0.051 vs 0.427 +/- 0.043, P < 0.05). CONCLUSIONS: A novel
      expression vector capable of generating specific 10-23DZ in cells has been
      successfully constructed. And the intracellular product 10-23DZ may inhibit the
      expression of any target gene of interest.

PMID- 20137275
TI  - [Altered expression of L-type calcium channel alpha1C and alpha1D subunits in
      colon of rats with diarrhea-predominant irritable bowel syndrome].
AB  - OBJECTIVE: To investigate the molecular identities of L-type calcium channel
      alpha1C subunit (Cav1.2) and alpha1D subunit (Cav1.3) responsible for motor
      dysfunction of diarrhea-predominant irritable bowel syndrome (D-IBS). METHODS: A
      total of 30 male Wistar rats were randomly divided into two groups. The
      traditional method for irritable bowel syndrome in a cold environment and
      intragastric administration of Folium Cassiae were combined to develop the D-IBS
      model. The fecal particles of rats and the water content in feces were measured.
      Then the expression of Cav1.2 and Cav1.3 mRNA was detected by reverse
      transcription polymerase chain reaction. The expressions of Cav1.2 and Cav1.3
      were examined by immunohistochemistry in colonic tissues from D-IBS model rats
      and matched tissues. RESULTS: The fecal particles and the water content in feces
      of D-IBS model rats significantly increased as compared with the normal rats (6.8
      +/- 1.4 vs 3.2 +/- 0.8, P = 0.032, 80% +/- 4% vs 47% +/- 5%, P = 0.018). Cav1.2
      and Cav1.3 were positively expressed in colon of both model group and control
      group rats. The immunohistochemical scores of Cav1.2 and Cav1.3 expression
      increased in colon of D-IBS model rats as compared with those in normal control
      rats (3.43 +/- 0.92 vs 2.82 +/- 0.60, P = 0.034, 4.32 +/- 0.51 vs 3.75 +/- 1.05,
      P = 0.039). The immunohistochemical scores of Cav1.3 expression were
      significantly higher than Cav1.2 in colon of both two group rats (P = 0.003,
      0.005). Similarly, the expression of Cav1.2 and Cav1.3 mRNA increased in colon of
      D-IBS model rats as compared with those in normal control rats (1.18 +/- 0.15 vs
      1.06 +/- 0.12, P = 0.023, 1.32 +/- 0.13 vs 1.23 +/- 0.13, P = 0.033). The
      expression of Cav1.3 mRNA was significantly higher than Cav1.2 in colon of both
      two group rats (P = 0.038, 0.012). CONCLUSIONS: The traditional modeling of
      irritable bowel syndrome in rats alters the expression of Cav1.2 and Cav1.3. It
      may be directly related to the generation of enhanced colonic contraction in D
      IBS. In addition, Cav1.3 may play a more important role than Cav1.2 in colonic
      contractility. It offers another potential therapeutic target in the treatment of
      irritable bowel syndrome.

PMID- 20137276
TI  - [Effect of benazepril on atrial cytoskeleton remodeling in the canine atrial
      fibrillation models].
AB  - OBJECTIVE: To investigate the effect of benazepril on atrial cytoskeleton
      remodeling in atrial fibrillation (AF) canines induced by chronic rapid atrial
      pacing (RAP). METHODS: Twenty canines were randomly divided into 3 groups: (1)
      Sham-operated group without RAP; (2) AF group: AF established by RAP at 600 beats
      per minute for 6 weeks; (3) Benazepril group: benazepril was dosed from 1 week
      pre-pacing to 6 weeks post-pacing. The diameter of atrial cardiomyocyte was
      measured, collagen volume fraction (CVF) analyzed by Masson staining and the
      expression and distribution of desmin were assayed by immunohistochemistry. RT
      PCR method was used to semi-quantify the mRNA expression of beta-tubulin and
      desmin. RESULTS: The diameter of atrial cardiomyocyte increased in AF group
      [LA:(27.9 +/- 3.8) microm; RA: (26.8 +/- 3.2) microm] and benazepril group[LA:
      (25.1 +/- 3.4) microm; RA: (25.2 +/- 3.5) microm] than sham-operated group [LA:
      (19.6 +/- 2.9) microm; RA: (18.7 +/- 2.6) microm] (P < 0.01). CVF increased in AF
      group than sham-operated group [LA: (16.9 +/- 1.1)% vs (9.2 +/- 0.9)%, RA: (15.7
      +/- 2.3)% vs (9.3 +/- 0.8)%, P < 0.01] and it decreased in benazepril group than
      AF group [LA: (11.3 +/- 0.8)% vs (16.9 +/- 1.1)%, RA: (10.9 +/- 0.8)% vs (15.7 +/
      2.3)%, P < 0.01]. Normal desmin cross-striations were lost in atrial
      cardiomyocyte and the desmin organization became irregular in AF group. The A
      values analyzed by immunohistochemistry of desmin increased in AF group than sham
      operated group and they decreased in benazepril group than AF group (P < 0.01).
      The expression of mRNA level of desmin and beta-tubulin were up-regulated in AF
      group than sham-operated group, (LA:1.0 +/- 0.3 vs 0.6 +/- 0.3, 0.9 +/- 0.4 vs
      0.6 +/- 0.3; RA: 1.0 +/- 0.6 vs 0.6 +/- 0.2, 1.1 +/- 0.3 vs 0.7 +/- 0.4, P <
      0.01) and they were down-regulated in benazepril group than AF group (LA:0.8 +/-
      0.4 vs 1.0 +/- 0.3, 0.7 +/- 0.3 vs 0.9 +/- 0.4; RA:0.7 +/- 0.3 vs 1.0 +/- 0.6,
      0.7 +/- 0.3 vs 1.1 +/- 0.3, P < 0.01). CONCLUSION: Benazepril can favorably
      improve atrial cytoskeleton remodeling in the canine atrial fibrillation model.

PMID- 20137277
TI  - [Effect of heparin upon inflammatory reaction of endotoxin-induced acute lung
      injury in rat].
AB  - OBJECTIVE: To investigate the effects of heparin upon inflammatory reaction and
      associated mechanism of endotoxin-induced acute lung injury (ALI) in rat.
      METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into three
      equal groups namely: ALI group, heparin treatment group and normal control group.
      The ALI rats were induced by injecting endotoxin intravenously and sacrificed at
      4 h after model establishment. The lung histology was scored by a modification of
      Smith technique. The albumin permeability of pulmonary microvascular (P(alb)) was
      measured by single nuclide tracer technique. Tumor necrosis factor alpha (TNF
      alpha), interleukin 6 (IL-6) and von Willebrand factor (vWF) levels of serum were
      determined using commercial enzyme-linked immunosorbent assay kits. The
      expressions of lung tissue extacellular signal-regulated kinases (ERK)-1/2, P38
      mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinases (JNK) were
      determined by Western blotting. RESULTS: The Smith lung injury score in heparin
      treatment group and ALI group were (5.00 +/- 1.26) and (8.00 +/- 1.09)
      respectively. The values were significantly higher than that of normal control
      group (0.67 +/- 0.52, both P < 0.01). However, the Smith lung injury score in
      heparin treatment group was significantly lower than that of ALI group (P <
      0.01). The P(alb), TNF-alpha, IL-6 and vWF of heparin treatment group were (0.28
      +/- 0.04), (1.92 +/- 0.35) microg/L, (1.22 +/- 0.13) ng/ml and (24.9 +/- 4.0) U/L
      respectively. The values were significantly higher than those of normal control
      group [0.20 +/- 0.02, (0.51 +/- 0.09) microg/L, (0.23 +/- 0.05) ng/ml and (14.0
      +/- 3.0) U/L respectively, all P < 0.01] but significantly lower than those of
      ALI group [(0.38 +/- 0.04), (2.77 +/- 0.37) microg/L, (1.62 +/- 0.13) ng/ml and
      (31.8 +/- 7.5) U/L respectively, all P < 0.01]. The lung tissue levels of phospho
      ERK1/2 and phospho-P38 MAPK expressions of heparin treatment group were markedly
      higher than those of normal control group, whereas markedly lower than those of
      ALI group. There was no marked difference of phospho-JNK expression in all three
      groups. CONCLUSION: Heparin markedly inhibits the expressions of phospho-ERK1/2
      and phospho-P38 MAPK, down-regulates the inflammatory reaction, attenuates the
      endothelial permeability of pulmonary vasculature and significantly improves
      endotoxin-induced lung injury in rats.

PMID- 20137278
TI  - [Prevention of blindness is still the great challenge faced by Chinese
      ophthalmology].
AB  - The prevention of blindness got the great progress recent five years. However,
      the situation of blindness and visual impairment didn't improve radically.
      According to the outcomes of Second National Survey of Disabled Persons in 2006,
      the prevalence of the visual disabled persons was 1.53%. The total number of
      visual disabled persons was 20.035 millions. The leading cause of the visual
      disabled was cataract. The progress for eliminating cataract blindness is
      relatively slow. The cataract surgical rate is lower. If pay no more attention to
      the prevention of blindness, the goal of 'Vision 2020' may not be reached by
      2020. Prevention of blindness is still a great challenge faced by Chinese
      ophthalmology. At present, some preparation have been made for the further
      activities of the prevention of blindness. The human and financial resources for
      the prevention of blindness are be developing. The reform of medical system in
      China is in favor to the activities of prevention of blindness in future. The
      development of the ophthalmic organizations can provide the enough professional
      personnel for the prevention of blindness. In the future activities of the
      prevention of blindness, the new mechanism is be facing to explore and construct
      for the persistent, efficient prevention of blindness. Recently, government
      launched the program 'Restore the vision for one million poor cataract blindness'
      is a momentous milestone affair in the prevention of blindness in China, which
      will promote the further activities for prevention of blindness.

PMID- 20137279
TI  - [Some aspects in planning and conducting a Chinese vision-related quality of life
      study].
AB  - The present paper concerns on some shortcoming of the planning and conducting
      steps in recent Chinese vision-related quality of life (VRQoL) studies, addresses
      the main application of VRQoL, introduces two instruments, these are
      questionnaire and utility value for VRQoL evaluation, the standard strategies for
      introducing or self-making questionnaire, and the principals of the conducting
      work.

PMID- 20137280
TI  - [A cross-sectional study on the prevalence of visual impairment in 2006 in Hubei
      province, China].
AB  - OBJECTIVE: To determine and compare the prevalence and causes of visual
      disability in urban and rural areas of Hubei province. METHODS: A cross-sectional
      study. From April 1 to May 31 in 2006, based on a stratified, multi-stage,
      cluster-sampling strategy, 31 counties (cities, districts), 124 townships (towns,
      streets), altogether 248 investigation districts, 101 674 sample individuals from
      Hubei province were selected to conduct inquiry registration, screening and
      visual disability evaluation. The revised 'Criteria of Disability' formulated by
      the specialist committee of the 2nd National Sample Survey of Disability was
      applied. The diagnosis and grading of visual disability were based on history of
      illness and vision function examination. The etiology diagnosis was made
      according to the causes of disability and the causing diseases. Chi-square test
      was used to investigate differences due to gender, age, and areas (urban and
      rural). RESULTS: The overall prevalence rate of visual disability in Hubei
      province is 1.40% (95%CI: 1.33% - 1.47%). The rate is 0.93% (95%CI: 0.88% -
      0.98%) for urban areas and 1.62% (95%CI: 1.24% - 2.00%) for rural areas. Rural
      areas have a higher rate than urban ones and the difference is statistically
      significant (chi(2) = 68.2410, P < 0.0001). The rate increases with age in both
      urban and rural areas. In age groups older than 10, the prevalence rate in rural
      areas is higher than urban areas, and the difference becomes significant (chi(2)
      = 33.6569, P < 0.0001) for age groups 30-80. Females have a higher rate (1.63%)
      than males (1.18%) (chi(2) = 37.8386, P < 0.0001). The main eye diseases causing
      visual disability in urban areas are cataract (53.77%), retinopathy and
      choroidopathy (10.82%), ametropia (7.87%), glaucoma (6.23%) and
      hereditary/congenital diseases and developmental disorders (5.90%). The main
      causing diseases in rural areas are cataract (48.61%), corneal diseases (14.17%),
      glaucoma (6.91%), retinopathy and choroidopathy (6.19%) and hereditary/congenital
      diseases and developmental disorders (5.20%). CONCLUSIONS: The rural areas have a
      higher prevalence rate of visual disability than urban areas in Hubei province.
      Cataract is the leading cause of visual disability. We should continue the work
      of prevention and cure of visual disability, the primary work being cataract
      surgery. More stress should be placed on the prevention and cure effort in rural
      areas and for females and elderly people.

PMID- 20137281
TI  - [A cross-sectional study on the visual disability of the residents in 2006 in
      Henan province, China].
AB  - OBJECTIVE: To explore the status on visual disability and the leading causes in
      residents in Henan Province. METHODS: It was a cross-sectional study and a part
      of the National Epidemiological Study on the disability in 2006. Sample size 120
      000 was assigned to Henan study by the protocol of the National epidemiological
      study on the disability. Stratified, equal interval, proportional probability;
      four-stage sampling was adopted. Survey teams were organized, and survey
      personnel was trained in the sampled counties and cities. Visual disabled persons
      were screened by home to home visit and confirmed by ophthalmologists. RESULTS:
      130 415 persons in 36 923 households were studied. 1973 persons were confirmed to
      have the visual disability, the prevalence was 1.51%. Among them, 1376 persons
      just suffer from the visual disability (simple visual disability), 579 persons
      had multiple disability including the visual disability (multiple disability).
      Among them, 643 persons (0.49%) were blindness, 1330 persons (1.02%) were low
      vision. The age of the most of the persons with visual disability was more than
      50 years old. The prevalence of the simple visual disability in male and female
      was 0.77% and 1.36% respectively and had significant statistical difference
      (chi(2) = 105.687, P < 0.01). The prevalence of the simple visual disability in
      urban and rural area was 0.58% and 1.15% respectively and also had significant
      statistical difference (chi(2) = 56.047, P < 0.01). The first five leading causes
      of the visual disability were cataract (54.69%), retinal and choroidal diseases
      (8.21%), corneal diseases (5.83%), genetic and congenital eye diseases (5.07%)
      and glaucoma (4.56%). CONCLUSION: Government and health organizations should pay
      more attention to the prevention and treatment the visual disability in Henan
      province, especially the prevention and treatment of cataract, retinal and
      choroidal diseases, corneal diseases, genetic and congenital eye diseases and
      glaucoma.

PMID- 20137282
TI  - [A prevalence survey of blindness and visual impairment in adults aged equal or
      more than 60 years in Beixinjing blocks of Shanghai, China].
AB  - OBJECTIVE: To investigate the prevalence rate of blindness and low vision and the
      leading cause of blindness in residents aged > or = 60 years in Beixinjing
      blocks, Shanghai. METHODS: A cross-sectional study was carried out by Shanghai
      First People's Hospital, affiliated Shanghai Jiaotong University and Shanghai
      Beixinjing Community hospital from November 2007 to April 2008. Randomly cluster
      sampling method was used, and all the individuals aged > or = 60 years in 8
      communities from Beixinjing blocks, Shanghai was enrolled in this study. The
      pinhole visual acuity and presenting visual acuity were measured separately in
      each eye. External eye, anterior segment and ocular fundus were examined by the
      ophthalmologist using slit lamp-microscopes, direct ophthalmoscopy and non
      mydriatic digital camara. Assigned ophthalmologic doctors assured the leading
      blind causes of every blind person. The survey was preceded by a pilot study
      where operational methods were refined and quality assurance evaluation was
      carried out. RESULTS: 3851 individuals were examined, and the response rate was
      92.73%. According to WHO diagnostic criteria: 29 persons were diagnosed as
      blindness, 11 male (37.93%) and 18 female (62.07%). 104 persons were diagnosed as
      low vision, 37 male (35.58%) and 67 female (64.42%). The prevalence rates of
      blindness and low vision were 0.75% and 2.70%. The leading causes of blindness
      were macular degeneration, cataract, corneal diseases, and retinal detachment.
      According to presenting vision diagnostic criteria: 61 persons were diagnosed as
      severe binocular blindness, 20 male (32.79%) and 41 female (67.21%). 66 persons
      were diagnosed as slight binocular blindness, 27 male (40.91%) and 39 female
      (59.09%). 276 persons were diagnosed as monocular blindness, 120 male (43.48%)
      and 156 female (56.52%). The prevalence of severe binocular blindness, slight
      binocular blindness and monocular blindness was 1.58%, 1.71% and 7.17%,
      respectively. The leading causes of blindness were macular degeneration,
      cataract, ametropia and corneal diseases. CONCLUSION: The leading cause of
      blindness was macular degeneration. The prevalence of degenerative retinopathy in
      this area is on the rise.

PMID- 20137283
TI  - [Epidemiologic study of conjunctivochalasis in populations equal or over 60 years
      old in Caoyangxincun community of Shanghai, China].
AB  - OBJECTIVE: To investigate the prevalence and relative factors of
      conjunctivochalasis among people over 60 years old in Caoyangxincun community of
      Shanghai. METHODS: A cross-sectional study based on local residents in this
      community was carried out from September 2008 to October 2008. Cluster sampling
      was used in randomly selecting individuals aged > or = 60 years. Slit-lamp
      ophthalmoscope was used for eye examination and diagnosis. The survey was
      preceded by a pilot study where operational methods were refined and quality
      assurance evaluation was carried out. A database was set using SPSS 10.0
      software, Chi-square test was used for data analysis. RESULTS: 2110 residents
      took part in this study, with the response rate 94.85%. 930 cases (1762 eyes)
      were confirmed as conjunctivochalasis, so the prevalence rate is 44.08%. The
      prevalence of conjunctivochalasis was increasing with age (chi(2) = 10.44, P <
      0.01). 556 cases (943 eyes) were confirmed as degree I, 246 cases (647 eyes) as
      degree II, 120 cases (162 eyes) as degree III and the rest 8 cases (10 eyes) as
      degree IV. Several symptoms, such as blurred vision, asthenopia and eye pain were
      more frequent in patient group than in the normal ones (chi(2) value was 15.44,
      20.54 and 19.74, respectively, P < 0.01). In the disease eyes, the conjunctiva
      usually piled up on the nasal and temporal side (944 eyes, 53.58%), the location
      of inferior lid margin was usually above corneal limbus (2589 eyes, 61.35%) and
      inferior lid margin entropion and introversion were always found (7.04% and
      6.63%). Abnormal lacrimal river was found in 87.23% of the diseased eyes, more
      than the non-conjunctivochalasis eyes (chi(2) = 1615.81, P < 0.01). CONCLUSIONS:
      Conjunctivochalasis is a common eye disease in aged population, with obvious
      signs and symptoms of ocular surface and lacrimal river impairment. In the local
      residents, most patients were classified as minimal or moderate degree. The
      location of inferior lid margin and the tension of inferior lid may be related
      factor of conjunctivochalasis.

PMID- 20137284
TI  - [Proliferative ability and ultramicrostructure of basal limbal epithelial cells
      in different age group of normal subjects].
AB  - OBJECTIVE: To demonstrate the difference in proliferative ability and
      ultramicrostructure of basal limbal epithelial cells in different age group of
      normal subjects. METHODS: It is a case-control study.40 specimens of limbus from
      40 eyes provided by the eye bank of Eye Ear Nose and Throat Hospital of Fudan
      University in 2007 - 2008 were enrolled in this study. Only one eye was enrolled
      from the same donner. Specimens were divided into 4 groups according to the
      donners' age: A (0 - 19 years), B (20 - 39 years), C (40 - 59 years) and D (60 -
      79 years). Immunohistochemistry of proliferating cell nuclear antigen (PCNA) was
      performed on 10 specimens of each group. The staining status of limbal epithelium
      was observed and the staining positive rate of the limbal basal epithelial cells
      was graded. And transmission electric microscopy was performed on specimens of
      each group. The morphologic feature of the ultramicrostructure of limbal basal
      epithelial cells were observed. RESULTS: 50% of specimens in group A showed a
      strong PCNA staining of (++++), while a weak staining of (+) took a main part in
      all the other 3 groups (B 40%, C 60% and D 50%, respectively). Furthermore,
      positive nuclear staining of limbal superficial cells was observed in 3 specimens
      and positive cytoplasm staining was observed in 1 specimen, all in group A.
      Transmission electric microscopy showed that the stem cell-like cells in group A
      possessed 3 morphologic features: extremely small, stretching along the basal
      membrane, with densely packed heterochromatin. In contrast, the stem cell-like
      cells in the other 3 groups did not show great disparity in cell size with their
      neighbor epithelial cells, and they stretched vertically to the basal membrane,
      with dispersed euchromatin. CONCLUSION: Difference in proliferative ability and
      ultramicrostructure of basal limbal epithelial cells was found in different age
      group of normal subjects.

PMID- 20137285
TI  - [Changes of the concentration of serum ischemia modified albumin and high
      sensitivity C-reactive protein in type 2 diabetic patients with retinopathy].
AB  - OBJECTIVE: To explore the changes of the concentration of serum ischemia modified
      albumin (IMA) and high sensitivity C-reactive protein (hs-CRP) in type 2 diabetic
      patients with retinopathy (DR). METHODS: The concentration of serum IMA and hs
      CRP in DR patients were determined by ELISA and rate nephelometry and compared
      with those in 83 no-DR (NDR) patients and 72 controls. The concentration of serum
      IMA and hs-CRP in 40 proliferative diabetic retinopathy (PDR) patients were
      compared with those in 39 no-PDR (NPDR) patients. Data was evaluated using
      analysis of PPMS version 1.5.Results are expressed as means + or - standard
      deviation of the mean. Statistical comparisons were performed by student's t-test
      or one-way analysis of variance followed by Dunnett's multiple comparison test
      and the means compared each other using q test. RESULTS: The serum IMA and hs-CRP
      concentration in DR patients were (46.51 + or - 13.29) microg/L, (4.27 + or -
      2.24) mg/L. The serum IMA and hs-CRP concentration in NDR patients were (25.47 +
      or - 9.33) microg/L, (2.96 + or - 1.84) mg/L. The serum IMA and hs-CRP
      concentration in controls were (15.36 + or - 4.27) microg/L, (1.86 + or - 0.97)
      mg/L. The serum IMA and hs-CRP concentration in PDR patients were (54.72 + or -
      15.61) microg/L, (6.34 + or - 3.53) mg/L. The serum IMA and hs-CRP concentration
      in NPDR patients were (38.35 + or - 11.27) microg/L, (3.28 + or - 1.77) mg/L. The
      serum IMA and hs-CRP concentration were significantly higher in DR patients than
      those in controls and NDR patients, the serum IMA and hs-CRP concentration in NDR
      patients were significantly higher than those in controls (F = 197.124, 34.561;q
      = 5.41-27.34; P < 0.01); the serum IMA and hs-CRP concentration were
      significantly higher in PDR patients than those in NPDR patients (t = 5.46, 4.89;
      P < 0.01); there was significant positive correlation between serum IMA
      concentration and hs-CRP concentration in DR patients (r = 0.617, P < 0.01).
      CONCLUSION: The serum IMA and hs-CRP concentration were significantly high in DR
      patients, and were positively associated with the seriousness of DR, which may
      contribute to the development of DR.

PMID- 20137286
TI  - [Slit lamp optical coherence tomography study of anterior segment changes after
      phacoemulsification and foldable intraocular lens implantation].
AB  - OBJECTIVE: To investigate quantitative changes of the anterior segment
      configuration after clear corneal incision phacoemulsification and foldable
      intraocular lens (IOL) implantation with slit-lamp-adapted optical coherence
      tomography (SL-OCT). METHODS: In prospective consecutive case series, clear
      corneal incision phacoemulsification and foldable intraocular lens implantation
      were performed in 44 eyes of 40 patients. The changes of the anterior segment
      configuration were performed by SL-OCT before and 1 day, 1 week, 2 weeks and 1
      month after surgery. SPSS 16.0 software was used to analyze statistical
      difference. RESULTS: For all patients, the central corneal thickness (CCT) and
      the incisional corneal thickness (ICT) increased significantly 1 day after
      surgery (CCT increased 99.59 microm, ICT increased 234.57 microm; P = 0.490). At
      1 month, the CCT almost had returned to baseline, but the ICT had been thicker
      about 19.25 microm than baseline(P = 0.001). The measurements of ACD, AOD500,
      AOD750, TISA500, TISA750 also increased significantly 1 day after surgery.
      Although the ACD had no changes within 2 weeks (all P < 0.05), it had been not
      stable. The changes of the width of the anterior chamber had been stable in the
      early period after surgery (all P > 0.05). CONCLUSION: The SL-OCT could
      impersonality and quantificationally evaluate the anterior segment changes
      induced by cataract surgery.

PMID- 20137287
TI  - [Clinical study of foldable TORIC intraocular lens implantation for corneal
      astigmatism correction].
AB  - OBJECTIVE: To discuss the result of TORIC intraocular lens (IOL) implantation to
      correct preexisting astigmatism in patients having cataract surgery. METHODS:
      This prospective series case study in Tianjin Medical University Eye Center
      included 61 eyes of 52 patients with more than 0.75 diopter (D) of preexisting
      corneal astigmatism having cataract surgery. The uncorrected visual acuity
      (UCVA), best corrected visual acuity (BCVA), residual cylinders, and TORIC IOL
      axis were measured preoperatively, 1 d, 1 month, 3 months post operatively.
      RESULTS: The UCVA was 0.5 or better in 92% of eyes and 0.8 or better in 78%. The
      mean refractive cylinder decreased significantly after surgery from (1.92 + or -
      0.83) D to (0.35 + or - 0.39) D (P < 0.01), which was no statistically
      significance with anticipated residual cylinder (0.37 + or - 0.42) D. The mean
      TORIC IOL axis rotation was 3.74 degrees + or - 4.71 degrees degrees at 1 d
      postoperatively, 92% of eyes deviated less than 10 degrees to the anticipated
      axis, from then on the IOL axis rotated 1.22 degrees + or - 2.53 degrees degrees
      till 3 months post operation. 98% of eyes rotated less than 10 degrees.
      CONCLUSIONS: The SN60TT TORIC IOL showed good stability. Phacoemulsification and
      posterior chamber TORIC IOL implantation is an safe and effective option to
      correct preexisting astigmatism in cataract patients.

PMID- 20137288
TI  - [Primary application and evaluation of a technology for objective measurement of
      accommodation of human eyes].
AB  - OBJECTIVE: To evaluate the practical value of a new technology for objective
      measurement of accommodation of human eyes. METHODS: It was a comparative study
      of some techniques for measuring the accommodation of human eyes. Twenty-six
      outpatients (20 male, 6 female, 10-37 years old) that were suspected to be
      abnormal in accommodation were examined with Nidek ARK-730 (with software AA-1
      inside). The measurement results from the instrument were compared by Kappa test
      with the clinical impression and comprehensive impression based on measurement
      results and clinical information. RESULTS: The abnormality rate of accommodation
      of the patients were 61.5%, 46.2%, 61.5% from the instrument, clinical impression
      and comprehensive impression respectively. The agreement was weak with Kappa
      value 0.244 between results from the instrument and clinical impression. The
      agreement was mild with Kappa value 0.513 between results from the instrument and
      comprehensive impression. The agreement was high with Kappa value 0.698 between
      results from clinical impression and comprehensive impression. CONCLUSIONS: The
      new technology is a progress and complementary to the traditional technology for
      accommodation examination. With the help of the new technology, some complicated
      patients could be diagnosed. The diagnose procedure of the instrument remains to
      be improved. The comprehensive impression based on measurement results and
      clinical information has more practical value.

PMID- 20137289
TI  - [Operation of cornea grafting micro-surgery robot system].
AB  - OBJECTIVE: To design the robotic mechanism of the cornea grafting micro-surgery
      system and evaluate its experimental feasibility and efficacy. METHODS: It was an
      experimental study. Based on computer assisted cornea grafting surgery (CACGS),
      the prototype about cornea grafting robot, which consists of six subsystems, was
      developed. The system was used for looping incision and suturing for 20 rabbit
      corneas. Experimental data were studied including the error of target incision
      position, the actual cutting depth and the cutting edge span in order to evaluate
      the system's clinical value. All above statistical descriptions were performed
      using SPSS software version 11.5. RESULTS: 20 corneas were looping incised and
      sutured by the robot-assisted cornea grafting micro-surgery system successfully.
      The error of target incision position was (0.356 + or - 0.040) mm. With CACGS,
      the cutting edge span (A) was (0.855 + or - 0.040) and the actual cutting depth
      error was less than 10 microm. Corneal structure and thickness was showed no
      change and cutting edge of cornea was displayed regularity in pathological
      examination. To suturing system, suturing span was (2.15 + or - 0.09) mm and the
      error of span (0.15 + or - 0.02) mm. CONCLUSIONS: The cornea grafting micro
      surgery system developed is used for cornea grafting of some animals
      successfully. The experiment results demonstrate the stability and efficiency of
      the robot.

PMID- 20137290
TI  - [Reconstruction of rabbit corneal stroma with skin fibroblasts].
AB  - OBJECTIVE: To explore whether skin fibroblasts could be used as a cell source for
      reconstruction of the corneal stroma. METHODS: It was an experimental study. Skin
      fibroblast cells were isolated from newborn rabbits, cultured and expanded in
      vitro. Cells were labeled with green fluorescence protein (GFP) gene by retro
      viral infection. Fibroblasts at passage 3 were seeded on polyglycolic acid (PGA)
      non-woven fibers to form a cell-scaffold construct. Constructs were then
      implanted into the adult rabbit corneal stroma layer after being cultured in
      vitro for 1 week. Engineered stroma were observed continuously and harvested
      after 8 weeks of transplantation for gross, histological evaluation and Keratocan
      examination. PGA alone was used as control. RESULTS: The engineered tissue in the
      cornea became transparent gradually over a period of 8 weeks. Histological
      analysis showed that engineered stromal lamellar was relatively regular and the
      orientation of fibers was parallel to the surface of cornea, which is similar to
      normal cornea. The implanted cells were confirmed by GFP expression under
      fluorescent microscope, which also express Keratocan. By transmission electron
      microscopy examination, no significant difference in the diameter of collagen
      fiber was observed between engineered stroma (33.08 + or - 2.47) nm and normal
      stroma (t = 1.80, P = 0.0771). CONCLUSION: Skin fibroblast cells could be used as
      seed cells for reconstruction of the corneal stroma.

PMID- 20137291
TI  - [Prevalence of trachoma in the world].
AB  - Trachoma is known as a chronic, epidemic and blindness eye disease, which is
      caused by Chlamydia trachomatis. The infection and transmission of trachoma have
      great relationship with environment, family and sanitation. Recently, there were
      reports continuously about the epidemic of trachoma in some countries and
      districts. So, it is still a remarkable problem to prevent and therapy trachoma
      in the world. The prevalence, risk factors, diagnosis, preventive and therapy of
      trachoma are summarized in the paper.

PMID- 20137292
TI  - [Progress in treatment of retinitis pigmentosa by neurotrophic factors].
AB  - Neurotrophic factors (NTFs) are pro-survival, pleiotrophic polypeptides which can
      play an important role in growth, differentiation and function maintenance of
      neurons. Many of them have been applied to treat various neurodegenerative
      diseases. Retinitis pigmentosa (RP), characterized by the impairment of
      photoreceptor-retinal pigment epithelium complex, is a retinal neurodegenerative
      disease with highly genetic heterogeneity. NTFs, one of the therapy approaches
      not targeting the mutation gene, have been proved to be effective in multiple
      types of animal models of retinal degeneration. Recent success in delivery of NTF
      genes by viral vectors or encapsulated cell technology (ECT) to degenerative
      retina provides an efficient administration approaches with great improvement in
      therapeutic effects. Further exploration for NTFs in the aspects of modulation of
      expression, location of receptors, signaling pathways, short- and long-term
      effects including side-effects will establish the foundation for clinical
      application of NTFs.

PMID- 20137293
TI  - [Update of fungal keratitis diagnosis and treatment].
AB  - The fungal keratitis is a common ocular disease, and its etiological factor and
      pathogenesis are definite, but the treatment is difficult and prognosis is poor.
      It is vital for fungal keratitis to be diagnosed rapidly and treated effectively.
      This paper had summarized the germ spectrum changes of fungal keratitis, new
      means of diagnosis adopted both in laboratory and clinical practices, such as
      improved staining method, confocal biomicroscope, technique of PCR and molecular
      sequence. There were some details of various new anti-fungal drugs and the
      available alternatives of surgical treatment for best treating effects.

PMID- 20137294
TI  - [A preliminary study on role of acid sphingomyelinase in receptor clustering
      induced by 50-Hz magnetic fields].
AB  - OBJECTIVE: To investigate the relationship among a 50-Hz MF-induced epidermal
      growth factor receptor (EGFR) clustering, acid sphingomyelinase (A-SMase) and
      ceramide (CER), and to explore the possible mechanism of receptor clustering.
      METHODS: Human amnion (FL) cells were exposed to a 50-Hz sinusoidal magnetic
      field at 0.4 mT for 15 min with or without imipramine, a specific inhibitor of A
      SMase and ceramide pretreatment. EGF treatment served as the positive control and
      DMSO treatment served as the solvent control. The EGFR was labeled with
      polyclonal anti-EGFR antibody and the clustering of EGFR was analyzed using
      immunofluorescence and confocal microscopy. The percentage of cells with EGFR
      clustering was counted and compared. RESULTS: Both EGF treatment and 50-Hz MF
      exposure could induce EGFR clustering. However, the effect could be eliminated by
      imipramine pretreatment for 4 hours. When FL cells were incubated with ceramide
      following the imipramine pretreatment for 30 min, EGFR clustering induced by 50
      Hz MF exposure could be recovered. CONCLUSION: EGFR clustering induced by 50-Hz
      MF depends on A-SMase activity, and ceramide, as the hydrolyzate from A-SMase
      might participate in the process of EGFR clustering.

PMID- 20137295
TI  - [Radiation protection and possible mechanisms for low intensity microwave].
AB  - OBJECTIVE: To investigate radiation protection and possible mechanisms of low
      intensity microwave on gamma-ray exposed mice. METHODS: 96 healthy Kunming mice
      were randomly divided into the following four groups: normal control, microwave
      (120 microW/cm(2), 900 MHz), gamma-ray irradiation (5 Gy), combined exposure of
      microwave and gamma-ray (120 microW/cm(2) + 5 Gy). The microwave group and
      combined group were exposed to 120 microW/cm(2) microwave firstly, 1 h/d, for 14
      days. Then the ionization and combined group were exposed to 5 Gy (60)Co gamma
      ray irradiation on the 15th day. Animals were sacrificed on the third, 6th, 9th
      and 12th day after irradiation. The sternum and spleen paraffin section were
      produced, and the histological changes were observed. Apoptosis rate of mice
      splenic cells in each group was examined by flow cytometry, and serum
      concentration of antioxidant and lipid peroxide was detected at the same time.
      RESULTS: Bone marrow was obviously injured either by radiation or microwave
      exposure, characterized by undergoing four-phase lesions, namely apoptosis
      necrosis, void, regeneration and recovery phase. Compared with the gamma-ray
      group, the pathological changes in combined group were slighter and the recovery
      was quicker. The pathological injuries of spleen were similar to that of bone
      marrow. Injuries in the combined group were slighter than gamma-ray group. It
      showed that apoptosis rate of splenic cells in combined group was significantly
      lower on the 6th and 9th day after gamma-ray radiation (23.02% +/- 15.18%, 25.37%
      +/- 11.62% respectively) from FCM results. Assays of oxidative damages suggested
      that serum superoxide dismutase (SOD) level in combined group increased while
      lipid peroxide level decreased significantly (P < 0.05). CONCLUSION: Low
      intensity microwave may exert protection effects on injuries induced by ionizing
      radiation. The underlying mechanisms might be related with suppression on the
      hematopoietic cells apoptosis induced by gamma-ray radiation, inhibition of
      oxidative damages, and thus enhanced reconstruction of the hematopoietic system.

PMID- 20137296
TI  - [Antagonistic effect of microwave on hematopoietic damage of mice induced by
      gamma-ray irradiation].
AB  - OBJECTIVE: To investigate antagonistic effect of microwave on hematopoietic
      damage of mice induced by gamma-ray irradiation. METHODS: Male healthy Kunning
      mice were treated with low dose microwave radiation before exposure to (60)Co
      gamma-ray irradiation of 8.0 Gy. The 30-day survival rate and average survival
      time of the mice after the treatment were examined. Peripheral blood parameters
      and the organ indexes of thymus and spleen were also observed in the irradiated
      mice. After exposure to 5.0 Gy gamma irradiation, indexes of hematopoietic foci
      formation of bone marrow cells (CFU-GM) and the proliferation activity of BMNCs
      were examined. The serum concentration of hemopoietic factors (GM-CSF and IL-3)
      were detected by ELISA kits. RESULTS: Pre-exposure with 120 microW/cm(2) 900 MHz
      microwave increased the 30-day survival rate (P < 0.05) and the number of white
      blood cells of gamma-ray treated mice. The increases of the organ indexes of
      thymus and spleen, proliferation activity of BMNCs and CFU-GM hematopoietic foci
      numbers, as well as the higher serum concentration of GM-CSF and IL-3 were
      observed in the microwave pre-exposure group. CONCLUSION: Low dose microwave
      radiation may exert potential antagonistic effects on hematopoietic injuries
      induced by ionizing radiation. The underlying mechanisms might be related with
      stimulation of hematopoietic growth factors expression, promotion of HSCs/HPCs
      proliferation, suppression on the reduction of HSCs/HPCs caused by (60)Co gamma
      ray, and enhanced construction of the hematopoietic system.

PMID- 20137297
TI  - [Effect of microwave radiation on primary cultured Sertoli cells].
AB  - OBJECTIVE: To explore whether microwave radiation may cause injury of primary
      cultured Sertoli cells. METHODS: The model of primary cultured Sertoli cells in
      vitro was established, which was radiated by microwave with average power density
      0, 30 and 100 mW/cm(2) for five minutes. The changes of cell cycle, apoptosis and
      death, and intracellular Ca2+ concentration in the Sertoli cells were measured at
      sixth hours through Annexin V-PI double labeling and Fluo-3-AM labeling, flow
      cytometry combined with laser scanning confocal microscopy after microwave
      exposure. RESULTS: The numbers of Sertoli cells were obviously reduced in G0-G1
      and G2-M phase (62.57% +/- 3.22% and 8.25% +/- 1.75%) and increased in S phase
      (29.17% +/- 4.87%) compared with the control groups (79.18% +/- 0.24%, 11.17% +/-
      0.50% and 9.64% +/- 0.62%) (P < 0.05 or P < 0.01), but the changes of rate of
      apoptosis and death and intracellular Ca2+ concentration showed no difference at
      6 h after exposure to 30 mW/cm(2) microwave. There was a significant increase in
      the Sertoli cell counts of G0-G1 phase (87.69% +/- 1.32%), and decrease in the
      Sertoli cell counts of G2-M and S phase (7.41% +/- 0.60% and 4.87% +/- 0.91%) (P
      < 0.01). There was also a significant increase in intracellular Ca2+
      concentration and rate of apoptosis and death (P < 0.05 or P < 0.01) at 6 h after
      exposure to 100 mW/cm(2) microwave. CONCLUSION: 100 mW/cm(2) microwave radiation
      may cause growth inhibition and increase of apoptosis and death in the primary
      cultured Sertoli cells. The increase of intracellular Ca2+ concentration is one
      of the injury mechanisms.

PMID- 20137298
TI  - [A aquaporin 4 expression and effects in rat hippocampus after microwave
      radiation].
AB  - OBJECTIVE: To investigate the expression of aquaporin 4 (AQP4) after microwave
      exposure and the correlation with the brain injury by radiation. METHODS: 70 male
      rats were exposed to microwave whose average power density was 0, 10, 30 and 100
      mW/cm(2) respectively. Rats were sacrificed at 6 h, 1 d, 3 d and 7 d after
      exposure. Immunohistochemistry and Western blot were used to detect the
      expression of AQP4 in protein level in rat hippocampus, and the expression of
      AQP4 in gene level was measured by in situ hybridization and RT-PCR. RESULTS: The
      expression of AQP4 in rat hippocampus was abnormal after 10, 30, 100 mW/cm(2)
      microwave exposure. The protein level showed increased at first and then
      recovered at 10 and 30 mW/cm(2) groups, while increased progressively in 100
      mW/cm(2) group within 14 d (P < 0.01). The gene expression of AQP4 was increased
      (0.51 +/- 0.02) at the beginning (6 h) and then regained after 10 mW/cm(2)
      microwave exposure, while in 30 and 100 mW/cm(2) groups, it rose to the peak at 7
      d (0.46 +/- 0.02 and 0.43 +/- 0.08) and didn't get back (P = 0.004; P = 0.012).
      CONCLUSION: Microwave radiation can increase the expression of AQP4 in rat
      hippocampus. The change might participate in the process of increasing
      permeability of blood-brain barrier and lead to the brain edema after microwave
      radiation.

PMID- 20137299
TI  - [Effects of electromagnetic pulse on blood-brain barrier permeability and tight
      junction proteins in rats].
AB  - OBJECTIVE: To study the effect of electromagnetic pulse (EMP) on the permeability
      of blood-brain barrier, tight junction (TJ)-associated protein expression and
      localization in rats. METHODS: 66 male SD rats, weighing (200 approximately 250)
      g, were sham or whole-body exposed to EMP at 200 kV/m for 200 pulses. The
      repetition rate was 1 Hz. The permeability of the blood-brain barrier in rats was
      assessed by albumin immunohistochemistry. The expression of typical tight
      junction protein ZO-1 and occludin in both cerebral cortex homogenate and
      cerebral cortex microvessel homogenate was analyzed by the Western blotting and
      the distribution of ZO-1 and occludin was examined by immunofluorescence
      microscopy. RESULTS: In the sham exposure rats, no brain capillaries showed
      albumin leakage, at 0.5 h after 200 kV/m EMP exposure for 200 pulses; a few brain
      capillaries with extravasated serum albumin was found, with the time extended,
      the number of brain capillaries with extravasated serum albumin increased, and
      reached the peak at 3 h, then began to recover at 6 h. In addition, no change in
      the distribution of the occludin was found after EMP exposure. Total occludin
      expression had no significant change compared with the control. However, the
      expression level of ZO-1 significantly decreased at 1 h and 3 h after EMP
      exposure in both cerebral cortex homogenate and cerebral cortex microvessel
      homogenate. Furthermore, immunofluorescence studies also showed alterations in ZO
      1 protein localization in cerebral cortex microvessel. CONCLUSION: The EMP
      exposure (200 kV/m, 200 pulses) could increase blood-brain barrier permeability
      in rat, and this change is associated with specific alterations in tight junction
      protein ZO-1.

PMID- 20137300
TI  - [Female genital toxicities of high-frequency electromagnetic field on rats].
AB  - OBJECTIVE: To study on the effects of sub-chronic exposures to high-frequency
      electromagnetic field (HF-EMF) on the estrous cycle, ovarian pathological changes
      and related hormones and preliminarily investigate the female genital toxicities
      of HF-EMF in rats. METHODS: 60 Wistar female adult rats were randomly divided
      into five groups based on body weight and radiated with different levels of 30
      MHz electromagnetic field (0, 25, 100, 400 and 1600 V/m) for eight hours daily.
      Weekly the rats were continuously exposed five days. From the 48th day the four
      stage of estrus cycle were observed with smear method of the vaginal cell. Fifty
      six days later the serum levels of sexual hormones were detected with the
      radioimmunoassay on estrus stage. The constituent ratio of the distinct follicle
      number on ovaries were observed with the HE staining and the ultrastructure was
      observed with the transmission electron microscope. Meanwhile, the ovarian humid
      weight and organ coefficient were observed. RESULTS: There was no significant
      difference in ovarian humid weight and organ coefficient between the exposure and
      the control groups. The time of proestrus in the 100 V/m group, the 400 V/m group
      and the 1600 V/m group was decreased significantly [(15.00 +/- 5.06), (11.40 +/-
      2.05) and (10.56 +/- 0.96) h in the exposure group compared with (18.70 +/- 2.96)
      h in the control group, P < 0.01], and the time of Anestrum in the 400 V/m group
      and the 1600 V/m group were increased significantly [(101.20 +/- 17.81) and
      (115.33 +/- 19.28) h in the exposure group compared with (69.80 +/- 11.42) h in
      the control group, P < 0.01)]. Serum LH in the 400 V/m and 1600 V/m group was
      increased significantly [(11.02 +/- 1.11) and (14.70 +/- 1.94) mU/ml in the
      exposure groups compared with (8.70 +/- 0.53) mU/ml in the control group, P <
      0.01], and serum E2 was decreased significantly [(57.16 +/- 31.56) and (50.57 +/-
      25.16) pg/ml in the exposure groups compared with (95.04 +/- 32.62) pg/ml in the
      control group, P < 0.01]. The composition ratio of the corpus luteum/albicans
      number in the 400 V/m group and the 1600 V/m group was increased significantly
      (19.75% and 19.04% in the exposure groups compared with 14.01% in the control
      group, P < 0.05). The composition ratio of the atretic follicle number was
      increased significantly in the 100 V/m, the 400 V/m and the 1600 V/m group
      (8.45%, 9.95% and 11.70% in the exposure groups compared with 7.72% in the
      control group, P < 0.01). The composition ratio of the mature follicle and the
      pri/sec follicle was decreased significantly in the 400 V/m and the 1600 V/m
      group (1.50% and 1.55% in the exposure groups compared with 3.36% in the control
      group. 22.24% and 21.09% in the exposure groups compared with 26.60% in the
      control group, P < 0.01). Along with the increase of radiation dose, the
      ultrastructure of cell on the ovaries appeared more abnormal. CONCLUSIONS: The
      toxicities of female gonads are closely associated with exposures to HF-EMF. The
      nonage damage of female gonadal toxicities might emerge on the ovaries.

PMID- 20137301
TI  - [Effects of 50 Hz sinusoidal magnetic field on Ca2+ release channel ryanodine
      receptor of sarcoplasmic reticulum vesicles].
AB  - OBJECTIVE: To investigate the effects of sinusoidal magnetic field on isolated
      sarcoplasmic reticulum (SR) calcium release channel (RyR1) function. METHODS:
      With the Ca2+ dynamic spectrum and isotope labeled methods, the Ca2+ release and
      [(3)H]-Ryanodine binding, the initial rates of NADH oxidation and the production
      of superoxide of SR exposed to 50 Hz sinusoidal magnetic field (MF) were
      investigated respectively. RESULTS: 0.4 mT, 50 Hz sinusoidal MF exposure for 30
      min increased SR Ca2+ release initial rate about 35% from (10.82 +/- 0.89)
      pmol.mg(-1) pro.s(-1) to (14.69 +/- 1.21) pmol.mg(-1) pro.s(-1); and the [(3)H]
      Ryanodine binding by about 15% from (2.13 +/- 0.05) pmol/mg pro to (2.45 +/-
      0.07) pmol/mg pro, which regulated by 1 mmol/L NADH with 1 mmol/L NAD+. Meanwhile
      MF upregulated the rate of NADH oxidation by about 22% from (0.88 +/- 0.11) x 10(
      4) FI/s to (1.07 +/- 0.13) x 10(-4) FI/s and upregulated the production of
      superoxide by about 32% from (0.99 +/- 0.09) x 10(-5) FI/s to (1.31 +/- 0.06) x
      10(-5) FI/s. CONCLUSION: 0.4 mT sinusoidal MF increases the activity of RyR1
      within the low redox potential environment, and promotes NADH oxidase activity
      and superoxide production.

PMID- 20137302
TI  - [Effects of occupational microwave irradiation on heat shock protein 70
      expressions in rat hippocampus].
AB  - OBJECTIVE: To study the change of heat shock protein (HSP)70 expression after
      exposure to occupational microwave in rats hippocampus, and explore the role of
      HSP70 in the mechanism of bio-effect of microwave irradiation. METHODS: The
      animal model was established by whole body exposures in 90, 5 W/cm(2) microwave
      irradiation field for 20 min in rats. Changes of the mRNA of hsp70 expressions in
      rat hippocampus at different time were studied by RT-PCR, and the protein change
      by Western blot. RESULTS: The mRNA and protein expression of hsp70 in rat
      hippocampus increased after 90 W/cm(2) and 5 W/cm(2) microwave irradiation for 20
      min. The anal temperature and the value of SAR increased significantly. These
      changes were positively correlated with power and irradiation time of microwave.
      The results indicated that microwave irradiation led to HSP70 syntheses
      effectively. CONCLUSION: Microwave irradiation can obviously induce the thermal
      effect and activate HSP70, and initiate the endogenous protective mechanism of
      central nervous system.

PMID- 20137303
TI  - [Effects of low concentration of chlorpyrifos prenatal exposure on generation
      mouse brain hippocampus and somatosensory cortex].
AB  - OBJECTIVE: To observe the effects of low concentration of organophosphate
      pesticide chlorpyrifos (CPF) prenatal exposure on generation mouse brain
      development. METHODS: 5 mg/kg CPF was administered daily on gestation days (GD)
      7.5 - 11.5. On postnatal day (PD) 35, quantitative morphologic examines were
      measured in CA1, CA3, dentate gyrus regions of the hippocampus and somatosensory
      cortex. RESULTS: After CPF prenatal exposure, selective morphology impairments
      were observed, showing 22.37%, 25.66% thinning of the CA1 and CA3 layers, 24.14%
      enlargement of the dentate guys and 81.77% to 74.61% decreasing of the ratio of
      neuron/glial of the somatosensory cortex. CONCLUSION: There maybe slight
      morphological changes after prenatal low concentration pesticide exposure even
      without obviously systemic toxicity.

PMID- 20137304
TI  - [Overview of chronic myelogenous leukemia and its current diagnosis and treatment
      patterns in 15 hospitals in China.].
AB  - OBJECTIVE: To explore demographic characteristics, current diagnosis and
      treatment patterns of chronic myelogenous leukemia (CML) patients in China.
      METHODS: Data of hospitalized CML patients in 2005 whole year and outpatient
      information (July 1 through September 30, 2006) from 15 hospitals throughout
      China were analyzed. RESULTS: A total of 1824 CML cases were analyzed, including
      722 inpatients and 1102 outpatients. The male/female ratio was 1.78:1. The median
      age at diagnosis was 40.02 (2.45 - 83.29) years old, 90.41% of the patients were
      diagnosed at chronic phase. Proportion of accelerated phase or blast crisis
      patients increased to 21.66% during study period. 93.20% of the patients received
      blood routine and bone marrow morphologic examination at diagnosis and in
      monitoring; 70.29% were performed cytogenetic analysis and 51.54% performed
      molecular measurement in addition. The most common therapy for CML treatment was
      hydroxycarbamide. The proportion of patients treated with imatinib and interferon
      was 37.45% and 25.55%, respectively. Of 722 inpatients, 164 (22.72%) received
      hemotopoietic stem cell transplantation (HSCT). The proportions of accelerated
      phase and blast crisis patients treated with imatinib were 48.28% and 48.42%,
      respectively, being significantly higher than that of chronic phase patients
      (35.9%) (P < 0.05). The mean imatinib dosage administered in the three phases
      patients did not differ significantly. Imatinib resistance rates were 6.87% and
      16.28% for outpatient and inpatient, respectively. In the outpatient group, the
      primary resistance to imatinib occurred comparably to the secondary resistance
      (68.75%), while primary resistance was predominant in inpatient group (65.71%).
      The intolerance rates of imatinib for outpatient and inpatient were 3.21%,
      11.63%, respectively. The majority of patients treated with imatinb were not
      monitored in time: 63.38% patients evaluated hematologic response after 3 months
      of treatment, proportions of patients received cytogenetic examination after 6
      months and 12 months of treatment were 41.41% and 27.35%, respectively. Mean cost
      for HSCT was 213 092 +/- 125 890 RMB. CONCLUSIONS: CML in China tends to afflict
      younger population than in Western countries. Most patients were diagnosed in the
      chronic phase. Due to restriction of financial support, only one third of CML
      patients were treated with imatinib, and the majority of the treated were not
      monitored in time. Clinicians should pay attention to resistance and intolerance
      to imatinib treatment in accelerated phase or blast crisis patients.

PMID- 20137305
TI  - [Combination of dexamethasone with IL-2 selectively induces the expansion of
      CD4(+)CD25(+)FOXP3(+) regulatory T cells in vivo and suppresses graft versus host
      disease.].
AB  - OBJECTIVE: To establish a method for increasing T regulatory cells (Treg) in the
      graft by using in vivo treatment with dexamethasone (Dex) plus IL-2 and observe
      its suppressing effect on graft-versus-host-disease (GVHD) in mice. METHODS:
      After treatment of male C57BL/6N mice (donor) with Dex (5 mgxkg(-1)xd(-1))
      combined with IL-2 (300 000 IUxmouse(-1)xday(-1)) for three days, spleen
      mononuclear cells were isolated for flow cytometry analysis of CD4(+)CD25(+)
      POXP3(+) Treg cells. The allogeneic lymphocytes were transplanted from male
      C57BL/6N mice to female BALB/c mice aged 8-12 weeks. GVHD and survival time were
      investigated after transplantation. Donor-derived hematopoiesis reconstituted in
      recipient mice was detected by Y-chromosome-specific PCR and H-2K(b) by flow
      cytometry. RESULTS: Administration of Dex and IL-2 markedly expanded functional
      CD4(+)CD25(+)FOXP3(+) Treg cells in murine spleen, the number of which in treated
      group was (24.2 +/- 7.6)% while in control group was (4.0 +/- 0.8)% (P = 0.01).
      The ratio of Treg to effector T cells (Teff) increased obviously in the treated
      group (0.43 +/- 0.15 vs 0.14 +/- 0.01, P = 0.01). In a murine allogeneic
      lymphocyte transplantation model, the grafts from donor with combined treatment
      of Dex and IL-2 led to a longer survival time than that from the control group
      (median survival time > 60 d vs 12 d, P = 0.0045), while the mortality rate was
      decreased (29.4% vs 71.4%, P < 0.05). CONCLUSION: Costimulation with Dex and IL-2
      can selectively expand the functional CD4(+)CD25(+)FOXP3(+) Treg in vivo, which
      can suppress acute GVHD.

PMID- 20137306
TI  - [Clinical significance of plasminogen activator inhibitor-1 (PAI-1) in the early
      development of HSCT-associated thrombotic complications.].
AB  - OBJECTIVE: To illustrate the early alteration of plasminogen activator inhibitor
      1 (PAI-1) in the recipients of hematopoietic stem cell transplantation (HSCT) and
      explore its clinical significance in transplantation-associated thrombotic
      complications. METHODS: Ninety-five patients undergoing HSCT were enrolled in
      this study. PAI-1 level and other hemostatic parameters were measured by enzyme
      linked immunosorbent assay (ELISA) in platelet poor plasma samples from patients
      on conditioning therapy and then weekly until four weeks after HSCT. RESULTS:
      Significant increase in PAI-1 was detected after conditioning treatment, followed
      by a diminution in the very week on transplantation (week 0), then increased with
      in time after transplantation. According to the occurrence of transplant
      associated complications, patients were classified into four groups: thrombus
      group ?[veno-occlusive disease (VOD) (n = 5), thrombotic microangiopathy (TMA) n
      = 1?], aGVHD group (n = 29), infection group (n = 19) and non-complication group
      (n = 41). One of 30 patients (3.3%) was diagnosed as thrombus in the auto-HSCT
      group, while five of 65 patients (7.7%) did in the allo-HSCT group. PAI-1 level
      of thrombotic patients was significantly increased compared with non-thrombotic
      subjects, and the patients without thrombotic complications have higher PAI-1
      level in the allo-HSCT group than in auto-HSCT group. All the patients with
      complications presented with significantly increased PAI-1 compared with those
      with no complications (P < 0.05). The six patients with thrombotic complications
      showed extremely elevated PAI-1 ?[(62.8 +/- 7.5) microg/L?] compared with that of
      aGVHD patients ?[(45.1 +/- 9.1) microg/L?] or infection patients ?[(50.0 +/-
      11.2) microg/L?] post-HSCT (P < 0.05). CONCLUSION: The increase in plasma PAI-1
      may be a specific mark for transplantation-associated thrombotic complications.
      Increased PAI-1 reflects the development of thrombotic complications. Extreme
      elevation of PAI-1 contributes to the early diagonsis of VOD and TMA after HSCT.

PMID- 20137307
TI  - [Prophylaxis of graft-versus-host disease in mice by chemical modification of
      graft and OX40-OX40L costimulatory pathway.].
AB  - OBJECTIVE: To explore the prophylaxis effect of pretreatment of allograft with
      methoxypolyethylene glycol-succinimidyl-propionic acid ester (mPEG-SPA) and anti
      OX40L monoclonal antibody (McAb) on acute graft-versus-host disease (aGVHD) after
      allogeneic bone marrow transplantation (allo-BMT) in mice. METHODS: Responder
      splenocytes from C57BL/6 donor mice (H-2(b)) were co-cultured with stimulator
      splenocytes from BALB/c recipient mice (H-2(d)) for 7 days in the presence or
      absence of anti-OX40L McAb followed by mPEG-SPA chemical modification. Donor bone
      marrow cells plus the mixed culture of T-cells were then transplanted into
      lethally irradiated BALB/c mice. The BALB/c recipient mice were divided into four
      groups: group A (allo-BMT control group), group B(mPEG-SPA modification group),
      group C (anti-OX40L McAb pretreated group) and group D (mPEG-SPA and anti-OX40L
      McAb dual-treated group). Survival time and survival rate of the recipients were
      observed after allo-BMT. GVHD was assessed by clinical signs and histological
      changes of skin, liver and small intestines. Enzyme-linked immunosorbent assay
      (ELISA) was used to detect cytokines (IL-4, IL-10 and INF-gamma) production. Flow
      cytometry (FCM) analysis was used to detect allogeneic chimerism. RESULTS: (1)
      The mice in group A developed typical clinical signs of aGVHD and all mice died
      within 17 days after BMT with an average survival time (AST) of (12.1 +/- 5.5)
      days. The signs of aGVHD were less evident in mice of groups B, C and D, and
      their AST (36.2 +/- 24.9, 32.0 +/- 24.8 and 44.3 +/- 23.2 days, respectively)
      were all longer than that in group A (P < 0.05). AST of group D being the longest
      (P < 0.05). The survival rates at day 60 post-BMT in groups B, C and D were 50%,
      41.7% and 66.7%, respectively. (2) Serum IFN-gamma level was increased after BMT
      in group A, and peaked in day 10 to day 15 post-BMT, while the level was
      decreased in groups B, C and D, reached the nadir on the day 10 post-BMT, with
      the lowest in group D (P < 0.01). After BMT, IL-4 and IL-10 levels were slightly
      decreased in group A, their levels were elevated in groups B and C (P < 0.05) and
      even more significantly increased in group D (P < 0.01). IL-4 and IL-10 levels
      peaked between day 10 and 15 post-BMT. (3) The average proportion of H-2(b)
      positive cells in recipient mice was 95% - 100% on day 60 post-BMT, with complete
      donor-type implantation. CONCLUSION: Combination of mPEG-SPA and anti-OX40L McAb
      can block T-cell activated antigens and co-stimulatory pathway, regulate the T
      cells differentiation and induce the immune shift of Th0 cells toward Th2 cells.
      The immune tolerance induced by this method can significantly relieve aGVHD after
      allo-BMT.

PMID- 20137308
TI  - [Relationship between CMV reactivation and KIR haplotype/HLA-Cw genotype in
      patients after unrelated-donor hematopoietic stem cell transplantation.].
AB  - OBJECTIVE: To explore the relationship between CMV reactivation and KIR haplotype
      or HLA-Cw genotype in patients after unrelated-donor hematopoietic stem cell
      transplantation (HSCT). METHODS: From January 2003 to December 2008 the HLA
      Cw/KIR genotype of 48 patient-donor pairs were determined by polymerase chain
      reaction with sequence specific primers (PCR-SSP) and sequence specific
      nucleotide (PCR-SSOP). Posttransplant CMV reactivation was performed by immune
      histochemically assay. RESULTS: Of 48 patients, 15 were transplanted from
      unrelated donors with an antigen mismatch for HLA Cw and 33 patient-donor pairs
      were matched for HLA-Cw. The CMV reaction rate was 66.7% for HLA-Cw mismatch
      group and 48.5% for HLA-Cw match group (chi(2) = 1.39, P = 0.2375). Thirty-seven
      donor-patients pairs belonged to group C1 and 11 to group C2, and CMV reaction
      rate was 64.9% in group C1 and 18.2% in group C2 (chi(2) = 18.13, P < 0.0001).
      Twenty-six patients received graft from KIR haplotype A (group A donor) and 22
      from KIR haplotype B donors (group B donor) and CMV reaction rate was 57.7% in
      group A donor and 50.0% in group B donor (chi(2) = 0.28, P = 0.5941). The number
      of donor activating KIRs (aKIRs) was less than that of recipient aKIRs in 34
      patient-donor pairs in which the CMV reaction rate was 70.6%, and the number of
      donor aKIRs was more than that of recipient aKIRs in 14 patient-donor pairs in
      which the CMV reactivation was 14.3%. There was a significan difference between
      the two group (chi(2) = 12.44, P = 0.0004). CONCLUSION: KIR and HLA-Cw genotypes
      influence the rate of CMV reactivation following non-T cell deleted unrelated
      donor hematopoietic cell transplantation.

PMID- 20137309
TI  - [Expression of cysteine rich 61 and vascular endothelial growth factor genes in
      patients with myelodysplastic syndromes and their relationship.].
AB  - OBJECTIVE: To explore the expression of Cysleine-rich 61(Cyr61) gene in the
      different subtypes of myelodysplastic syndromes (MDS), and the significance of
      Cyr61 in the genesis progression, and transformation of MDS and the relationship
      between Cyr61 and vascular endothelial grown factor (VEGF). METHODS: Reverse
      transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical S-P were
      used to detect mRNA and protein expressions of Cyr61 and VEGF in bone marrow
      mononuclear cells (BMMNC) from 28 MDS, 12 acute myeloid leukemia (AML) patients,
      and 10 normal volunteers. RESULTS: Expressions of Cyr61 and VEGF were higher in
      MDS and AML patients than in controls (P < 0.05). The expressions of Cyr61 and
      VEGF were significantly higher in high risk group (0.3998 +/- 0.2647, 0.4775 +/-
      0.1342) than that in low risk MDS group (0.2213 +/- 0.1465, 0.2872 +/- 0.2341) (P
      < 0.05), but no significant difference between high risk MDS and AML patients.
      Expressions of Cyr61 and VEGF protein were higher in MDS patients than in normal
      controls (P < 0.05), and were significantly higher in high risk MDS group ?[(38.7
      +/- 2.9)%, (43.2 +/- 2.7)%?] than in low risk group ?[(31.4 +/- 3.1)%, (33.5 +/-
      3.4)%?] (P < 0.05). Expressions of Cyr61 and VEGF were significantly correlated
      (r = 0.8762, P < 0.01). CONCLUSION: Cyr61 and VEGF may play a role in the
      angiogenesis and pathogenesis of MDS.

PMID- 20137310
TI  - [Combination of rabbit antithymocyte globulin plus cyclosporin A as first-line
      immunosuppressive therapy for the childhood with severe aplastic anemia.].
AB  - OBJECTIVE: To analyse the efficacy and side-effects of rabbit antithymocyte
      globulin (ATG) and cyclosporin A (CsA) as the first-line therapy for childhood
      severe aplastic anemia (SAA). METHODS: Seventy-one childhood SAA patients treated
      with rabbit ATG + CsA as first line therapy were retrospectively analysed.
      RESULTS: Seventy-one SAA patients, including 38 SAA and 33 very severe aplastic
      anemia (VSAA), were enrolled. The median age was 12 years. Of these patients, 3
      died within 3 months after the immunosuppressive therapy (IST). The overall
      response rate was 67.6% (46/68) and the median time to transfusion independent
      was 53 days. Thirty-three patients (48.5%) obtained remission in 3 months after
      the IST and 45 (67.2%) in 6 months. The response rates were 57.7% (15/26), 56.5%
      (13/23) and 94.7% (18/19) for patients less than 10 years old, 10 - 15 year-old
      and 15 - 18 year-old, respectively. Sixty patients suffered from serum sickness
      on the IST. Three patients relapsed and another 3 unrespond patients received
      retreatment of IST, and one patient progressed to myelodysplastic syndromes
      (MDS). CONCLUSION: Rabbit ATG in combination with CsA as first line therapy for
      childhood SAA/VSAA can lead to overall response rate of 67.6% with minor adverse
      effects.

PMID- 20137311
TI  - [2-methoxyestradiol disrupts aggresomes induction by bortezomib and potentiates
      apoptosis in multiple myeloma cells.].
AB  - OBJECTIVE: To investigate the synergistic anti-multiple myeloma (MM) effect of 2
      methoxyestradiol (2-ME2) and bortezomib, and explore the relationship between
      this effect and blockade of aggresomes formation by 2-ME2. METHODS: Four MM cell
      lines RPMI-8226, NCI-H929, U266 and SKO-007 were used for study.
      Immunoflourescent anti-ubiquitin and Hoechst 33342 staining were used to examine
      aggresome-positive cells and apoptotic cells, respectively. Isobolographic
      analysis was used for determination of synergy. RESULTS: (1) Quantitative assay
      showed that in the absence of bortezomib, only 6.6% - 8.9% of MM cells were
      aggresome-positive, but the percentage was increased to 71.9%-83.4% after
      treatment with bortezomib at IC(20) concentration for 24 h. Aggresome-positive
      cells with immunoreactivity to anti-ubiquitin were detected in almost all non
      apoptotic cells, but not in apoptotic cells. (2) Treatment in a definite range of
      concentrations bortezomib plus 2-ME2 led to MM cell apoptosis compared with each
      agent alone and the significantly synergistic effect confirmed by isobolographic
      analysis. (3) Combination of bortezomib and 2-ME2 increased the apoptotic cells
      aggresome-negative cells (ANK) and decreased the non-apoptotic cells in aggresome
      positive cells (APC). In RPMI8226 and U266 cells, the apoptotic cells in ANC
      increased from (14.5 +/- 2.0)% and (20.1 +/- 2.9)% to (80.7 +/- 6.9)% and (71.6
      +/- 6.2)%, and the non-apoptotic cells in APC decreased from (75.3 +/- 5.7)% and
      (69.1 +/- 8.6)% to (13.8 +/- 3.8)% and (19.5 +/- 4.2)%, respectively, in combined
      group and bortezomib alone group. CONCLUSION: Bortezomib-induced aggresomes have
      a protective function for MM cells and combination of bortezomib with 2-ME2
      induced a synergistic cytotoxicity to the cells.

PMID- 20137312
TI  - [Telomere length measurement of 10 Chinese patients with bone marrow failure
      syndrome.].
AB  - OBJECTIVE: To measure telomere length of patients with bone marrow failure
      syndrome (BMFS) and explore the relationship between telomerase gene mutation and
      telomere shortening. METHODS: Blood samples from 10 patients with AA, MDS-RA were
      collected and performed TERC and TERT gene mutation analysis. Telomere length was
      measured by Southern blot and compared with normal controls and two patients with
      MDS-RAEB and AML each. RESULTS: Two patients in the 10 BMFS patients had TERC and
      TERT gene mutations and very short telomeres compared with normal controls and
      with the 8 BMFS counterparts, the telomere length was less than 50% of that of
      normal control, and was similar to that of patients with MDS-RAEB and acute
      myelogenous leukemia, indicating the possibility of malignant transformation.
      Some BMFS patients with no mutations also had short telomeres. CONCLUSIONS: BMFS
      patients with telomerase gene mutation have very short telomeres, being similar
      to that of hematological malignancies. Some BMFS patients with no telomerase gene
      mutations also have short telomere length.

PMID- 20137313
TI  - [To advance the standardization and internationalization of interventional
      treatment of structural heart disease in China].

PMID- 20137314
TI  - [Summary of the eleventh National Congress of Cardiology of Chinese Medical
      Association].

PMID- 20137316
TI  - [Current status and prospect of transcatheter intervention of congenital heart
      disease].

PMID- 20137315
TI  - [Aspirin in first prevention for cardiovascular disease:present and future].

PMID- 20137317
TI  - [Current status and advancement of transcatheter aortic valve replacement].

PMID- 20137318
TI  - [Review and prospect of interventional therapy for valvular heart diseases].

PMID- 20137319
TI  - [Analysis of complications during and post interventional therapy of congenital
      heart disease].
AB  - OBJECTIVE: To analyze the incidence and cause of complications during and after
      interventional therapy for congenital heart disease (CHD). METHODS: From April
      1986 to April 2009, 388 out of 6029 patients with CHD developed complications
      during and post interventional therapy, another 5 patients died post procedure,
      clinical data from these 393 patients were retrospectively analyzed. The patients
      with severe functional insufficiency requiring intervention or surgery during and
      after interventional therapy were classified as severe complications. RESULTS:
      The overall complication rate was 6.44% [7.69% post atrial septal defect
      occlusion, 4.20% post patent ductus arteriosus (PDA) occlusion, 1.31% post
      percutaneous balloon pulmonary valvuloplasty, 14.94% post ventricular septal
      defect occlusion, 3.13% post percutaneous closure of aortopulmonary collaterals,
      30.95% post catheter embolotherapy of pulmonary arteriovenous malformations,
      12.50% post transcatheter closure of coronary artery fistulae, 20.00% post
      transcatheter closure of ruptured sinus of Valsava aneurysm, 66.67% post
      percutaneous balloon aortic valvuloplasty]. The severe complication rate was
      0.65%(39/6029). The procedure-related mortality rate was 0.08% (5/6029), 0.26%
      (2/761) post percutaneous balloon pulmonary valvuloplasty, 0.05% (1/2070) post
      PDA occlusion, 9.10% (1/11) post balloon atrial septostomy, 33.33% (1/3) post
      percutaneous balloon aortic valvuloplasty. Emergency Cardiovascular surgery rate
      was 0.22% (13/6029). Selective surgery was required in 0.13% (8/6029) of patients
      post procedure. Two patients (0.03%) received permanent pacemaker implantation.
      CONCLUSIONS: The severe complications and mortality rate of interventional
      therapy for CHD are relative low. Post procedure follow-up is needed fro
      monitoring possible procedure-related complications.

PMID- 20137320
TI  - [Factors influencing the choice of atrial septal occluder for transcatheter
      closure of secundum atrial septal defects].
AB  - OBJECTIVE: To analyze factors influencing the choice of atrial septal occluder
      (ASO) for transcatheter closure of patients with secundum atrial septal defect
      (ASD). METHODS: A total of 1114 ASD patients [388 males, aged from 2 to 75 years,
      mean age (26.3 +/- 17.0) years] were enrolled. Patients were divided to adult (>
      14 years, mean 34.4 years, n = 779) and child (< or = 14 years, mean 7.3 years, n
      = 335) groups. ASD size in different ultrasound cross-sections was determined by
      transthoracic echocardiography (TTE). ASO size was chosen on the basis of the
      maximum diameter of the defect (MD). Defect-shapes and rim lengths of ASD, the
      difference choice of ASO in the two groups were compared. RESULTS: MD of the
      defects ranged from 5 to 40 mm [mean (19.7 +/- 7.8) mm]. ASD was successfully
      occluded in 1085 out of 1114 patients (97.4%). Occluder size ranged from 6 to 46
      mm [mean (25.8 +/- 8.9) mm] and the difference between occluder size and MD
      ranged from 2 to 10 mm [mean (6.1 +/- 3.4) mm, ASO/MD ratio 1.3:1]. Though the
      diameter of the defect was similar between the 2 groups, the size of occluder was
      significantly larger in adult group than that in child group (ASO/MD ratio 1.1 -
      1.6:1 vs. 1.2 - 1.8:1, P < 0.05). MD was significantly correlated with ASO in
      both groups (r = 0.911 and r = 0.944 in adults and child groups, respectively,
      all P < 0.01). The size and increment of the occluder used in patients with
      deficient anterior rims was significantly bigger than patients with sufficient
      anterior rims (P < 0.01). CONCLUSION: The maximum diameter of the defect was the
      major determinant for selecting occluder size and choice of occluder size was
      also influenced by patient age, defect-shape and defect rim for transcatheter
      closure of secundum ASD.

PMID- 20137321
TI  - [One-stop hybrid cardiac surgery for neonates and young children with congenital
      heart disease].
AB  - OBJECTIVE: To summarize our 5 years experiences of one-stop hybrid procedure
      (OHP) for the management of congenital heart disease (CHD) in neonates and young
      children (< 2 years old). METHODS: Clinical data derived from consecutive 152
      young children and neonates with CHD underwent OHP between March 2004 to March
      2009 were analyzed. Patients were divided into 3 groups: Balloon plasty group (n
      = 72), device closure group (n = 43) and collateral arteries occlusion group (n =
      37). All procedures were image-guided and performed in a specially designed
      hybrid operation room. Incidence of major adverse cardiovascular events was
      obtained. RESULTS: Patients received successful per-ventricular valvuloplasty or
      per-aortic balloon angioplasty in balloon plasty group. Two patients in this
      group with severe right ventricle outflow obstruction received regular open-heart
      outflow tract reconstruction immediately (n = 1) or selective conventional open
      heart operation after discharge (n = 1). One neonate with pulmonary atresia with
      intact ventricular septum died from liver failure 6 month after OHP. In device
      closure group, device closure was failed in 3 cases (2 with atrial and 1 with
      ventricular septum defects), 1 young child with ventricular septum defects died
      from pneumonia after successful device closure. No device malposition was
      observed in device closure group during the follow-up. All patients received
      major collateral arteries occlusion and open-heart correction were discharged
      without complication. CONCLUSION: OHP could avoid or shorten the application of
      cardiopulmonary bypass and reduce the surgical trauma in selected young children
      with CHD. Although OHP was feasible and safe, the image outfits, image-guided
      technology and OHP-related device should be further developed and improved for
      better procedure outcome.

PMID- 20137322
TI  - [Prognostic impact of heart block during transcatheter closure of ventricular
      septal defect].
AB  - OBJECTIVE: To investigate the prognostic impact of heart block during the
      transcatheter closure of ventricular septal defect (VSD). METHODS: Forty three
      patients developed complete left or right bundle branch block (CLBBB, CRBBB),
      incomplete left or right bundle branch block (ILBBB, IRBBB), and atrioventricular
      block (AVB) during and within 1 week post procedure were followuped at 1, 6, 12,
      24, 36, 48 and 60 months post procedure. Electrocardiogram, dynamic
      electrocardiogram and transthoracic echocardiography were made. RESULTS: Bundle
      branch block and atrioventricular block were detected in 26 patients (CLBBB n =
      4, CRBBB n = 5, ILBBB n = 2, IRBBB n = 10 and third-degree AVB n = 5) during the
      transcatheter closure of VSD, and in 17 patients (CLBBB n = 5, CRBBB n = 2, first
      degree AVB n = 3, second-degree I-type AVB n = 1 and third-degree AVB n = 6)
      within 1 week post procedure. Heart block disappeared in 33 patients (76.7%)
      before discharge, in 37 patients (86.1%) at 1 month and in 41 patients (95.4%) at
      6 months post procedure. CLBBB or CRBBB was seen in two cases at 24 months after
      closure. There was no heart failure and serious cardiac dilatation during follow
      up. CONCLUSION: The heart block occurred during the periprocedure period of
      transcatheter closure of VSD was a benign phenomenon without prognostic
      importance.

PMID- 20137323
TI  - [Long-term outcome of percutaneous balloon mitral valvuloplasty in patients with
      rheumatic mitral valve stenosis].
AB  - OBJECTIVE: To observe the outcome of percutaneous balloon mitral valvuloplasty
      (PBMV) in patients with rheumatic mitral valve stenosis. METHODS: From April 1992
      to November 2008, 1768 patients underwent PBMV in our hospital.Clinical and
      echocardiographic follow up data were analyzed in 426 patients from April 1992 to
      August 1998. Left atrial pressure and the mitral valve gradient (MVG) were
      measured before and immediately after PBMV in all patients. RESULTS: PBMV was
      successful in 1748 out of 1768 patients (98.86%). Left atrial pressure decreased
      from (38 +/- 7) mm Hg (1 mm Hg = 0.133 kPa) to (12 +/- 4) mm Hg (P < 0.001), MVG
      decreased from (28 +/- 6) mm Hg to (8 +/- 3) mm Hg (P < 0.001) and the area of
      the mitral valve increased from (0.98 +/- 0.26) cm(2) to (1.97 +/- 0.39) cm(2) (P
      < 0.001) post PBMV. The main complications included death (n = 2), acute
      pericardial effusion (n = 1), severe mitral regurgitation (n = 12), cerebral
      embolism (n = 2) and pulmonary edema (n = 1). Ten years follow up was finished in
      426 patients and 288 patients (67.6%) were still in NYHA class Ior II without
      mitral valve replace operation or repeated PBMV, restenosis was evidenced in 140
      patients (33.3%) and 31 patients dead (7.5%). CONCLUSION: PBMV was an effective
      therapy option for patients with rheumatic mitral valve stenosis.

PMID- 20137324
TI  - [Effects of transcatheter closure of patent ductus arteriosus in 139 adult
      patients].
AB  - OBJECTIVE: To analyze the clinical feature and the effects of transcatheter
      closure of adult patients with patent ductus arteriosus (PDA). METHODS: Between
      January 2000 and April 2009, 139 patients [22 male, aged from 40 to 74: (49.8 +/-
      6.8) years] with PDA were hospitalized in our hospital. Clinical data and effects
      of transcatheter closure of PDA were analyzed. RESULTS: There were 64 patients
      with NYHA classI, 53 with class II, 16 with class III and 6 with class IV before
      procedure. In 139 patients, pulmonary arterial hypertension (PAH) was found in
      107 out of 139 patients (77.0%). Transcatheter PDA closure was not performed in 3
      patients due to severe PAH and successfully performed in the remaining 136
      patients (97.8%) without major complications. Post procedure aortic angiography
      evidenced minor residual shunt in 14 cases, small residual shunt in 2 cases and
      moderate shunt in 1 case. The NYHA class was significantly improved and the PAH
      significantly reduced [sPAP: (47.3 +/- 23.9) mm Hg (1 mm Hg = 0.133 kPa) vs.
      (28.1 +/- 12.3) mm Hg, P < 0.01] post procedure. CONCLUSION: PAH and heart
      failure were commonly associated with PDA in adult patients. Transcatheter PDA
      closure is safe and effective in these patients except those with severe PAH.

PMID- 20137325
TI  - [A case of small heart syndrome].

PMID- 20137326
TI  - [Experience of transcather closure in patients with postinfarction ventricular
      septal defects].
AB  - OBJECTIVE: To evaluate the therapeutic effect of transcather closure in patients
      with postinfarction ventricular septal defects (VSD). METHODS: Transcatheter VSD
      closure was performed in 12 patients with postinfarction VSD (10 muscular and 2
      membranes defects) on top of standard pharmacotherapy and percutaneous
      transluminal coronary angioplasty (PTCA) as indicated. RESULTS: (1) Percutaneous
      interventional VSD closure was successful in 9 out 12 patients (75%) and these 9
      patients survived post procedure. (2) The medial time between VSD occurrence and
      closure was (15.5 +/- 9.2) days. Procedure-related complications such as device
      embolization and malignant arrhythmia occurred in 3 patients (25%). The medial
      time between procedure and discharge from hospital was (11.3 +/- 5.2) days. (3)
      Coronary angiography was performed in 2 patients and 4 stents were implanted in
      diseased lesions. CONCLUSION: Transcatheter closure could be successfully
      performed in selected patients with postinfarction VSD.

PMID- 20137327
TI  - [Outcome of percutaneous balloon pulmonary valvuloplasty for patients with
      pulmonary valve stenosis].
AB  - OBJECTIVE: To assess the effects of percutaneous balloon pulmonary valvuloplasty
      (PBPV) for patients with pulmonary valve stenosis (PS). METHODS: From February
      1996 to March 2003, 65 patients with isolated PS were diagnosed by
      echocardiography and received PBPV in our department, clinical data were analyzed
      in this study. RESULTS: Age of 65 patients ranged from 1 to 48 years [mean (13.5
      +/- 9.3) years]. The pulmonary transvalvular gradient (PTG) was (86.4 +/- 33.6)
      mm Hg(1 mm Hg = 0.133 kPa) and the right ventricular systolic pressure was (107.5
      +/- 36.5) mm Hg before PBPV. Single-balloon valvuloplasty was performed in 41
      patients, double-balloon valvuloplasty in 6 patients and Inoue-balloon
      valvuloplasty in 18 patients. The ratio of balloon/valve ranged from 1.00 to 1.19
      in 19 patients, from 1.20 to 1.39 in 42 patients, and greater than 1.40 in 4
      patients. The procedure was classified as successful when the RV-PA gradient was
      < 36 mm Hg post procedure, 6 to 12 months follow up was finished after PBPV by
      catheterization or echocardiography in 25 patients. Immediate post procedure
      success rate was 81.5% (53/65). The lowest PTG immediately post procedure was
      seen in Inoue balloon group and balloon/valve ratio between 1.20 to 1.39 group.
      Post procedure, tricuspid valve regurgitation was evidenced in 2 patients,
      reactive right ventricular outflow tract stenosis was shown in 26 patients (13
      from Inoue group) and pulmonary regurgitation was detected in 3 patients. The
      mean PTG was (35.7 +/- 23.9) mm Hg at follow-up. PTG gradually reduced to normal
      in 6 patients with post procedure PTG > or = 36 mm Hg. Right ventricular outflow
      tract stenosis was attenuated in all 11 followuped patients. There was no
      restenosis during follow-up. CONCLUSION: Percutaneous balloon valvuloplasty was
      effective and safe for treating patients with pulmonary valve stenosis. Superior
      outcome was linked with balloon/valve ratio between 1.20 to 1.39 and Inoue
      balloon valvuloplasty in this cohort.

PMID- 20137328
TI  - [Impact of antihypertensive medication timing on degree and stability of blood
      pressure lowering in patients with essential hypertension].
AB  - OBJECTIVE: To investigate the impact of antihypertensive medication timing on
      degree and stability of blood pressure (BP) lowering in patients with moderate
      and severe essential hypertension. METHODS: Ninety patients were randomly
      assigned to take Valsartan and Felodiping together in the morning (group A),
      Valsartan in the morning and Felodiping in the evening (group B) or Felodiping in
      the morning and Valsartan in the evening (group C, n = 30 each). The morning
      dosage was titrated if the goal blood pressure was not achieved. Ambulatory blood
      pressure monitoring (ABPM) was performed on the first and 14(th) day of
      medication. RESULTS: The BP reductions during nighttime and twenty-four in group
      B and C hours were similar (P > 0.05) but were significant more than those in
      group A (P < 0.05). The smoothness indexes of mean systolic, mean arterial blood
      pressure during nighttime and twenty-four in group B and C were similar but
      significantly higher than that in group A (P < 0.05). The smoothness index of
      diastolic pressure at nighttime in group B and C was similar but significantly
      higher than that in group A (P < 0.05). CONCLUSION: More significant and stable
      antihypertensive effects could be achieved by taking the two antihypertensive
      medications separately in the morning and at evening compared that taken the two
      drugs together in the morning.

PMID- 20137329
TI  - [Extracorporeal membrane oxygenation in the peri-operative period of heart
      transplantation].
AB  - OBJECTIVE: To summarize and analyze clinical outcomes and experience about using
      extracorporeal membrane oxygenation (ECMO) in supporting heart transplant
      patients in the peri-operative period of in Fuwai Hospital retrospectively.
      METHODS: We performed 131 orthotopic heart transplantations from June 2004 to
      December 2008. Fourteen cases used veno-artery ECMO (Medtronic Ltd) for
      mechanical circulatory support in the peri-operative period of heart
      transplantation. Active clotting time(ACT) was maintained between 160 - 200
      seconds, mean blood flow was 1.8 - 3.3 L/min during ECMO assistant period.
      RESULTS: Twelve survivals discharged with NYHAI, two patients died of multiple
      orgen failure with severe infection and complication of central nervous system.
      The ECMO time was 75 - 824 h and mean time 149 h. 12 survivals with ECMO
      assistance decreases the dose of vasoactive drugs, after bedside UCG evaluating
      heart function recovery with stable circulation, ECMO could be weaned off
      uneventfully after 100 h. Five patients with seven times bleeding complication
      and one patient with catheter-associated arterial thrombosis of distal limb, all
      ECMO patients with low-albuminemia and hyperbilirubinemia at some degree, eleven
      patients with increasing blood creatine and five patients were treated with
      continous renal replacement therapy, one patient with pertinacious
      hyperbilirubinemia was treated with plasma exchange and molecular absorbent
      recirculating system. Seven patients were extension incision healing and six
      patients were tracheotomy. CONCLUSIONS: ECMO can bridge patients with end-stage
      heart failure to heart transplant, and extend the use of marginal donors, grasp
      the ECMO indication and timing of application, avoiding irreversible dysfunction
      of the vital organs and preventing complication during ECMO, ECMO may decrease
      mortality of severe patients in the peri-operative period of heart
      transplantation.

PMID- 20137330
TI  - [Association between clinical ischemic events and carotid calcification evaluated
      by 64 slices CT angiography].
AB  - OBJECTIVE: To explore the relationship between clinical ischemic events and
      carotid calcification detected by 64 slices CT angiography. METHODS: We
      retrospectively analyzed the carotid calcified plaques in 116 patients underwent
      the 64 slices CT angiography. The relationship between the carotid calcification
      and the clinical ischemic events was analyzed. RESULTS: A total of 377 plaques
      were detected and the incidence of carotid plaque calcification was 63.40%.
      Incidence of plaque calcification was significantly lower in patients with ages <
      50 years than that in patients with ages 51 - 59 years, 60 - 69 years and higher
      than 70 years (P = 0.003, P = 0.002, P = 0.000, respectively). The incidence of
      plaque calcification in the common carotid artery was significantly lower than
      the carotid bifurcation (P = 0.000) and the internal carotid artery (P = 0.000).
      The incidences of calcification in the mild, moderate and severe degree of
      stenosis and occlusion were 46.54%, 33.33%, 26.67% and 0% respectively. The
      distribution of intraplaque calcium was similar between patients with ischemic
      event and non-ischemic event group. However, the incidence of calcification was
      significantly lower patients with ischemic event than that in patients without
      ischemic event (30.34% vs. 43.10%, P = 0.013). Calcified plaque was negatively
      associated with ischemic event (beta = -0.688, P = 0.006). CONCLUSION: 64 slices
      CT angiography can analyze the characterization of carotid plaque calcium.

PMID- 20137331
TI  - [Safety and feasibility of transradial coronary angiography at the outpatient
      clinic].
AB  - OBJECTIVE: To evaluate the safety and feasibility of transradial coronary
      angiography at the outpatient clinic. METHODS: From February 2007 to June 2007,
      100 outpatients who received transradial coronary angiography in Anzhen hospital
      were included in this analysis, 100 inpatients underwent coronary angiography
      were selected as control group. Primary endpoints included success rate, percent
      of angiographic catheter use with different diameters, adverse events during the
      procedure (such as death, malignant arrhythmia, acute myocardial infarction,
      coronary artery spasm, coronary artery dissection, perforation or occlusion,
      etc.) and after the procedure (such as death, acute myocardial infarction, upper
      limb haematoma, osteofascial compartment syndrome, radial artery pseudoaneurysm
      or occlusion, etc.). RESULTS: The success rate (100% vs. 100%), procedure
      duration time [(12.5 +/- 3.4) min vs.(10.8 +/- 3.6) min, P = 0.517] and
      exposition time [(4.3 +/- 1.0) min vs. (4.1 +/- 1.0) min, P = 0.629] were similar
      between the outpatient and inpatient groups. Radial and coronary artery spasm
      were the main adverse events during the angiography, and haematoma was the main
      adverse event after the angiography. There were no significant differences of
      adverse events between the 2 groups. The total cost of the outpatient group was
      significantly lower than the inpatient control group [(4012 +/- 238) yuan vs.
      (5329 +/- 371) yuan, P < 0.001]. Expenditure including chemical tests, medicine,
      nursing care, room and board all decreased significantly. CONCLUSION: Transradial
      coronary angiography application at the outpatient clinic was safe and feasible
      for stable patients, and this procedure could decrease the medical expenditure
      and shorten the admission time.

PMID- 20137332
TI  - [Evaluation of left ventricular diastolic function using velocity vector imaging
      and quantitative tissue velocity imaging].
AB  - OBJECTIVE: To validate the efficacy of velocity vector imaging (VVI) and
      quantitative tissue velocity imaging (QTVI) for evaluating left ventricular
      diastolic function. METHODS: Fifty-one patients underwent left heart
      catheterization were included in this study. Mean of peak early diastolic
      velocity (Em), EF and the ratio of early (E) to late (A) mitral valve flow
      velocity (E/A) were measured by echocardiography and the ratio of E to Em (E/Em)
      was calculated. Left ventricular end diastolic pressure (LVEDP) was measured
      during catheterization examination. RESULTS: E/Em derived from VVI or QTVI was
      significantly correlated with LVEDP (r = 0.808, P < 0.01 and r = 0.692, P < 0.01,
      respectively) and the correlation coefficient between VVI and LVEDP was
      significantly higher than that between QTVI and LVEDP (Z = 2.246, P = 0.025). Em
      derived from VVI and QTVI also negatively correlated with LVEDP (r = -0.740, P <
      0.01 and r = -0.567, P < 0.01) and the correlation coefficient between VVI and
      LVEDP was significantly higher than that between QTVI and LVEDP (Z = 2.595, P =
      0.009). However, there was no correlation between E/A and LVEDP (r = 0.117, P =
      0.415). CONCLUSION: E/Em and Em derived from VVI and QTVI are valuable parameters
      for evaluating LV diastolic function.

PMID- 20137333
TI  - [Ghrelin down-regulates ACAT-1 in THP-1 derived foam cells via growth hormone
      secretagogue receptor-dependent pathway].
AB  - OBJECTIVE: To investigate the effects of Ghrelin on the expression of acyl
      coenzyme A:cholesterol acyltransferases-1 (ACAT-1) in THP-1 derived foam cells.
      METHODS: The human monocytic leukemia cell line (THP-1) was chosen in our study.
      The differentiation of THP-1 cells into macrophages was induced by phorbol 12
      myristate 13-acetate. Macrophages were then incubated with oxidized LDL (ox-LDL)
      to generate foam cells. Ghrelin and [D-Lys3]-GHRP-6, the special antagonist of
      growth hormone secretagogue receptor (GHS-R), were treated during foam cells
      formation. The ACAT-1 protein and mRNA levels were detected by Western blot and
      RT-PCR. The effect of variance of cholesterol content was measured by
      zymochemistry via-fluorospectrophotometer. RESULTS: Ghrelin reduced the content
      of cholesterol ester in foam cells obviously. ACAT-1 protein and mRNA levels were
      also decreased. The antagonist of GHS-R inhibited the effects of Ghrelin on ACAT
      1 expression in dose-dependent manner. The ACAT-1 mRNA levels of the GHS-R
      specific antagonist groups (10(-5), 5 x 10(-5), 10(-4) mol/L) were 1.14 +/- 0.04,
      1.58 +/- 0.03, 2.40 +/- 0.16, significantly higher than that of the Ghrelin group
      (0.89 +/- 0.05). And the protein expressions were 1.25 +/- 0.09, 1.77 +/- 0.11,
      2.30 +/- 0.09, also higher than that of the Ghrelin group (0.86 +/- 0.08).
      CONCLUSIONS: Ghrelin might interfere atherosclerosis by down-regulating the
      expression of ACAT-1 via GHS-R pathway.

PMID- 20137334
TI  - [Thrombolysis of rabbit's pulmonary embolism with thrombus-targeted urokinase
      immune liposome].
AB  - OBJECTIVE: To develop thrombus-targeted urokinase immune liposome through
      incorporating D-dimer monoclonal antibody (DDmAb) to liposome and observe the
      thrombolytic efficiency in a rabbit pulmonary thromboembolism (PE) model.
      METHODS: Reverse-phase evaporation method was used to develop targeted urokinase
      immune liposome by coupling DDmAb to urokinase liposome (liposomal-encapsulated
      urokinase) with glutaraldehyde. The PE models were induced by injecting 4
      autologous emboli (2 mm x 5 mm) through jugular vein catheter into pulmonary
      arteries. New Zealand white rabbits (n = 32) were randomized into four groups: A
      group (TBS), B group (150 000 IU/kg UK), C group (30 000 IU/kg urokinase
      liposome) and D group (30 000 IU/kg urokinase immune liposome). The right
      ventricular pressure and the emboli size in pulmonary arteries were determined.
      RESULTS: The right ventricular pressure increased significantly in PE rabbits (P
      < 0.01), the average value is (6.75 +/- 6.82) mm Hg (1 mm Hg = 0.133 kPa). Eighty
      minutes post various treatments, right ventricular pressure remained unchanged as
      post PE in group A [(40.15 +/- 11.22) mm Hg vs. (41.67 +/- 14.23) mm Hg],
      decreased to baseline level in group B and D [(34.71 +/- 8.67) mm Hg vs. (33.98
      +/- 9.32) mm Hg, (30.65 +/- 6.67) mm Hg vs. (30.77 +/- 6.85) mm Hg, all P >
      0.05], decreased but not returned to normal value in group C. Residual emboli
      size remained unchanged in group A and partly reduced in group C and more
      significantly reduced in group B and D. Hemorrhage of heart, kidney and liver was
      evidenced in group A but not in other groups. CONCLUSION: Acute PE could be
      successfully treated by the thrombus-targeted urokinase immune liposome with D
      dimer monoclonal antibody.

PMID- 20137335
TI  - [Annexin A5 inhibits homocysteine-induced tissue factor expression and activity
      in vascular smooth muscle cells].
AB  - OBJECTIVE: The expression of tissue factor (TF) in vascular smooth muscle cells
      (VSMCs) plays an important role in the pathogenesis of artherosclerosis (AS) and
      thrombosis. Hyperhomocysteinemia is a risk factor for AS. Annexin A5, a calcium
      dependent anionic-phospholipid-binding protein has anticoagulant effect mediated
      by its interaction with phosphatidylserine. We investigated the effects of
      Annexin A5 on homocysteine (Hcy)-induced TF expression and activity in VSMCs.
      METHODS: Human umbilical artery VSMCs were cultured by tissue explanting method,
      incubated with Hcy at various concentrations in the absence and presence of
      Annexin A5 (50 microg/ml)/mono-TFAb (10 microg/ml). Flow Cytometry (FCM) was used
      to detect the expression of TF on the surface of VSMCs. Protein expression of TF
      was detected by Western blot. Determination of TF activity by factor Xa
      generation. RESULTS: The expression level of TF protein on the surface of the
      resting VSMCs was low [the positive rate was (4.01 +/- 2.11)%] and could be
      upregulated by Hcy [peaked at 1000 micromol/L, the positive rate was (37.67 +/-
      4.96)%]. Annexin A5, as well as mono-TFAb could significantly inhibit Hey-induced
      TF membrane expression, release activity and protein expression. CONCLUSIONS:
      These results suggest that Annexin A5 could inhibit Hcy-induced expression and
      activity of TF in VSMCs as well as TF release of VSMCs. Annexin A5 might play an
      active role on attenuating AS and reducing coronary thrombosis by inhibiting TF
      pathway.

PMID- 20137336
TI  - [Successful ablation of complicated supraventricular tachycardia under the CARTO
      system guidance in one patient].

PMID- 20137337
TI  - [A case of primary cardiac lymphoma].

PMID- 20137338
TI  - [A case of retroperitoneal fibrosis].

PMID- 20137339
TI  - [Progress of beta(1) adrenergic receptor gene polymorphism in cardiovascular
      field].

PMID- 20137340
TI  - [The clinical significance of early repolarization derived from
      electrocardiology].

PMID- 20137341
TI  - [Principles and some related problems of target delineation in radiotherapy for
      esophageal cancer].

PMID- 20137342
TI  - [Silencing of cell cycle checkpoint kinase gene enhances cisplatin-induced
      apoptosis of lung cancer cells].
AB  - OBJECTIVE: To investigate the changes in cell cycle induced by cisplatin (DDP)
      and the effect of antisense oligonucleotide (AsODN) targeting Chk1/2 on DDP
      induced apoptosis in lung cancer cell line A549 cells. METHODS: The
      characteristics of cell cycle and apoptosis induced by DDP were detected by flow
      cytometry using SubG1 method. Chk1/2 mRNA and protein expression were assayed by
      RT-PCR and Western blot under best condition of transfection of AsODN targeting
      Chk1/2 by lipofection. Apoptosis of A549 cells induced by DDP was determined by
      flow cytometry using AnnexinV-FITC staining after transfection of Chk1/2 AsODN.
      RESULTS: Asynchronized A549 cells were treated with 10 micromol/L DDP, and
      significant S-phase arrest was observed at 12 h later. Transfection with
      antisense oligonucleotide targeting Chk1/2 inhibited the Chk1/2 expression at
      both mRNA and protein levels. Either Chk1 or Chk2-specific AsODN consistently
      enhanced DNA damage-induced apoptosis by 100% - 200%, compared with that in the
      sODN control (P < 0.05), but combined use of Chk1- and Chk2-specific AsODN did
      not show synergistic effects as compared with that induced by treatment with Chk1
      or Chk2-specific AsODN alone (P > 0.05). CONCLUSION: Chk1 and Chk2 may be
      regarded as effective targets of chemotherapy for lung cancer. Silencing the key
      effector Chk1 and Chk2 genes may significantly increase the chemosensitivity of
      lung cancer cells.

PMID- 20137343
TI  - [Effects of gambogic acid on the regulation of steroid receptor coactivator-3 in
      A549 cells].
AB  - OBJECTIVE: To investigate the effects of gambogic acid (GA) on the proliferation
      inhibition and apoptosis induction in Human lung adenocarcinoma A549 cells in
      vitro, as well as the regulation of steroid receptor coactivator-3 (SRC-3) to
      explore the relationship between them. METHODS: The effect of GA on the growth of
      A549 cells was studied by MTT assay. Apoptosis was detected by Hoechst 33258
      staining. The localization of SRC-3 was determined by confocal laser scanning
      microscopy. Western blot and RT-PCR technique were applied to assess the
      expression of SRC-3. RESULTS: GA presented a striking proliferation inhibition
      potency on A549 cells in vitro, as well as apoptosis induction activity in a time
      and dose-dependent manner. The IC(50) value for 24 h was (3.17 +/- 0.13)
      micromol/L. Overexpression of SRC-3 was found in A549 cells, whereas the SRC-3
      protein and mRNA expression levels were significantly downregulated in A549 cells
      induced by GA in a dose-dependent manner. The location of SRC-3 was situated
      mainly in the cell nuclei. CONCLUSION: GA exhibits a potent proliferation
      inhibition and apoptosis induction in human lung adenocarcinoma A549 cells, which
      might correspond to the downregulation of the expression of SRC-3. Thus, it
      promises to be a new target drug for lung cancer treatment.

PMID- 20137344
TI  - [Silencing of Adrm1 by RNA interference suppresses proliferation of colorectal
      cancer cells].
AB  - OBJECTIVE: To investigate the effects of the novel proteasome subunit Adrm1
      knockdown by RNA interference on proliferation of colorectal cancer cells.
      METHODS: The shRNA eukaryotic expression vector against Adrm1 was constructed and
      transfected into colon cancer RKO cells. The Adrm1-shRNA stable transfected
      clones were selected. Experimental cells were divided into 3 groups: the
      experimental group containing stable Adrm1-shRNA transfected cells, the control
      group containing only RKO colon cancer cells and stable empty vector transfected
      control group. The Adrm1 protein expression level was analyzed by Western blot.
      The colony-forming ability of the three groups was assessed by soft agar assay.
      The cell proliferation and apoptosis were analyzed by methyl thiazolyl
      tetrazolium (MTT) method and in situ end labeling (TUNEL) assay. Cell cycle
      changes were assayed by flow cytometry. RESULTS: Adrm1-shRNA effectively
      suppressed Adrm1 expression in the experimental group. Silencing of Adrm1 in RKO
      cells significantly inhibited their anchorage-independent growth, only occasional
      individual colonies were formed. The apoptosis rate of experimental group was
      (12.4 +/- 1.1)%, significantly higher than that of the stable empty vector
      transfected control group. The proportion of G(0)/G(1) and S/G(2) phase cells in
      the experimental group was (41.2 +/- 1.1)% and (58.8 +/- 1.1)%, respectively. The
      cells were arrested at G(1) phase. In addition, Adrm1 RNA interference combined
      with 5-Fu treatment significantly suppressed colorectal cancer cell growth in
      vitro. CONCLUSION: Silencing of Adrm1 by RNA interference can significantly
      suppress proliferation of RKO cells through inducing apoptosis and arresting the
      cell cycle. The combined application of Adrm1 RNA interference and chemotherapy
      may become as a novel therapeutic strategy for Adrm1 overexpressed colorectal
      cancer.

PMID- 20137345
TI  - [Mechanism of anti-tumor effect of HIF-1alpha silencing on cervical cancer in
      nude mice].
AB  - OBJECTIVE: To observe the anti-tumor effect of silencing the expression of HIF
      1alpha on cervical cancer in nude mice and to explore its mechanism of action.
      METHODS: Human cervical cancer cell line Siha cells were divided into 3 groups:
      mock control group, control group transfected with scrambled sequence plasmid,
      and experimental group transfected with pU-HIF-1alpha-shRNA eukaryotic expression
      plasmid. Cultured cells of the three groups were inoculated in nude mice to
      establish cervical cancer-bearing nude mice. HIF-1alpha RNAi assay was performed
      to evaluate the tumor-suppressive effect of HIF-1alpha silencing on cervical
      cancer-bearing nude mice. Immunohistochemistry and Western blot were used to
      observe the distribution and protein expression of HIF-1alpha and GLUT1, while RT
      PCR was adopted to detect the gene expression of HIF-1alpha, GLUT1 and HKII. The
      product of glycolysis (lactic acid) and apoptosis in tumor cells were detected by
      colorimetry and semi-quantitative TUNEL staining, respectively. RESULTS: The
      tumor growth in experimental group was significantly slower than that in the two
      control groups (P < 0.05). On the 50th day after transplantation, the tumor
      weight in the experimental group was (1.90 +/- 0.28) g, significantly lower than
      (2.95 +/- 0.77) g in the control group and (2.54 +/- 0.56) g in the mock group (P
      < 0.01). In the experimental group, the gene and protein levels of HIF-1alpha
      were 0.45 +/- 0.04 and 1.25 +/- 0.92, and the levels of GLUT1 were 0.32 +/- 0.02
      and 1.25 +/- 0.48, respectively. Both indicators in HIF-1alpha and GLUT1 were
      lower than that in the two control groups (P < 0.05). The expression levels of
      HKII gene and lactic acid in the experimental group were lower than that in the
      two control groups (P < 0.05), but the apoptotic cells were much more numerous in
      the experimental group than that in matched control groups (P < 0.01).
      CONCLUSION: The gene therapy by siRNA targeted silencing of HIF-1alpha may down
      regulate its downstream genes GLUT1 and HKII expression, therefore, to reduce the
      tumor glycolysis activity and promote tumor cell apoptosis, and exert a tumor
      suppressing effect in vivo.

PMID- 20137346
TI  - [Inhibitory effect of low molecular weight heparin on the secretion of vascular
      endothelial growth factor by tumor cells in vitro].
AB  - OBJECTIVE: To investigate whether low molecular weight heparin (LMWH) may
      suppress the expression and secretion of vascular endothelial growth factor
      (VEGF) from tumor cells in vitro and inhibit the VEGF-induced proliferation of
      human tumor vascular endothelial cells. METHODS: Human lung cancer cell line
      A549, human liver cancer cell line HepG2, human colon carcinoma cell lines HCT116
      and HCT8 were used in this study. The expression levels of VEGF and TNF-alpha
      (tumor necrosis factor-alpha) in the tumor cells with or without pretreatment of
      LMWH/heparin were measured by standard sandwich ELISA technique. The VEGF mRNA
      level of HepG2 cells cultured with or without LMWH/heparin was determined by RT
      PCR and real time PCR. Human umbilical vein endothelial cells (HUVEC) were
      cultured in tissue culture medium (TCM) with or without LMWH/heparin for 3 days.
      Then non-radioactive cell proliferation assay (MTS) kit and cell cycle assay by
      flow cytometry were performed to measure the proliferation of HUVEC. RESULTS: The
      VEGF levels in the control, LMWH, and heparin groups of the pulmonary
      adenocarcinoma cell line A549 were (1045.89 +/- 165.30) pg/ml, (782.45 +/- 67.17)
      pg/ml and (916.54 +/- 71.25) pg/ml, respectively. The VEGF levels in the control,
      LMWH, and heparin groups of the colon adenocarcinoma cell line HCT116 were
      (955.76 +/- 51.14) pg/ml, (822.89 +/- 142.39) pg/ml and (951.77 +/- 188.22)
      pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups in
      the colon adenocarcinoma cell line HCT8 were (1290.62 +/- 41.23) pg/ml, (1063.34
      +/- 63.82) pg/ml and (1257.14 +/- 11.40) pg/ml, respectively. The VEGF levels in
      the control, LMWH, and heparin groups in the liver cancer cell line HepG2 were
      (1083.00 +/- 134.35) pg/ml, (758.00 +/- 84.85) pg/ml and (874.00 +/- 22.62)
      pg/ml, respectively. The VEGF expression levels in the above mentioned cell lines
      cultured in TCM were significantly reduced in the LMWH-treated groups compared
      with that of the control group (P < 0.05). But the level of TNF-alpha in TCM
      cultured cells was unaffected by LMWH. The VEGF mRNA was reduced in the LMWH
      treated HepG2 cell line. Moreover, TCM exhibited stimulating effect on
      proliferation of HUVEC and the effect was significantly impaired by LMWH
      treatment. Flow cytometric analysis revealed that LMWH treatment arrested HUVECs
      at the G1 phase of cell cycle. CONCLUSION: LMWH can suppress the expression and
      secretion of VEGF by tumor cell lines and therefore have a potential inhibiting
      effect on angiogenesis induced by VEGF.

PMID- 20137347
TI  - [Association of single nucleotide polymorphism of MnSOD gene with carcinogenesis
      and development of esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the association of single nucleotide polymorphism (SNP)
      of manganese superoxide dismutase (MnSOD) gene with carcinogenesis and
      progression of esophageal squamous cell carcinoma. METHODS: The MnSOD9 T-->C SNP
      was genotyped by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis in 103 patients with esophageal squamous cell
      carcinoma and 195 healthy controls. RESULTS: A significant difference was
      observed in the MnSOD allelotype distribution among esophageal squamous cell
      carcinomas and healthy controls (chi(2) = 4.645, P < 0.05). Individuals with the
      9 C allele had a significantly higher risk to develop esophageal squamous cell
      carcinoma compared with those with the TT allele. The frequency of C allelotype
      among patients with lesions of different lengths (</= 5 cm and > 5 cm) was 16.3%
      and 36.7%, respectively. A significant difference was observed in the MnSOD
      allelotype distribution between patients with lesions of different lengths
      (chi(2) = 5.147, P < 0.05). No significant association of the MnSOD polymorphism
      at 9 T-->C with the tumor site, maximal length and clinical staging was found in
      esophageal squamous cell carcinoma. CONCLUSION: Single nucleotide polymorphism
      (SNP) of MnSOD gene may be correlated with the susceptibility and disease
      progression of esophageal squamous cell carcinoma, and may become a tumor marker
      for prediction of this cancer.

PMID- 20137348
TI  - [Lung adenocarcinoma stem cell phenotypes and their correlation with patient
      prognosis].
AB  - OBJECTIVE: To detect the cancer stem cells and to evaluate their prognostic
      implication in patients with lung adenocarcinoma. METHODS: Three phenotypic
      markers of cancer stem cells (SP-C, CCSP and OCT4) in lung adenocarcinoma were
      detected by immunofluorecence staining. The correlation among the
      clinicopathological parameters and phenotypes of cancer stem cells as well as
      survival were analyzed by Cox proportional hazard method. RESULTS: Of the 57
      cases, cancer stem cells were detected in 52, including OCT4(+)
      bronchioloalveolar stem cell (BASC) phenotype (SP-C(+) CCSP(+) OCT4(+)) in 40
      cases and OCT4(-) BASC phenotype (SP-C(+) CCSP(+) OCT4(-)) in 12 cases.
      Statistical analysis revealed that the phenotype of cancer stem cells was related
      with the cellular differentiation, i.e. the OCT4(+) BASC phenotype occurred more
      frequently in the well-differentiated tumors, while the OCT4(-) BASC phenotype
      usually presented in most of the poorly-differentiated ones. Cox analysis showed
      that the OCT4(+) BASC phenotype was one of prognostic factors. CONCLUSION: The
      lung adenocarcinoma stem cells have phenotypic features of bronchioalveolar stem
      cells (SP-C(+) CCSP(+)). The expression of self-renewal regulatory gene OCT4 in
      these cells indicates an aggressive nature and unfavorable prognosis.

PMID- 20137349
TI  - [Expressions of Ep-CAM and cyclin D1 and their clinical significance in
      gallbladder carcinoma].
AB  - OBJECTIVE: To investigate the expressions of Ep-CAM and cyclin D1 and their
      correlation with the clinicopathological factors and prognosis in gallbladder
      carcinoma. METHODS: Ep-CAM and cyclin D1 expressions were detected by PV6000
      immunohistochemical staining in 60 gallbladder carcinoma and 15 para-cancerous
      mucosa specimens. RESULTS: Ep-CAM and cyclin D1 expressions were detected in
      56.7% and 48.3% of the cancer tissues, respectively, significantly higher than
      those in the normal mucosa (P < 0.05). Ep-CAM expression was not correlated with
      clinicopathological data, however cyclin D1 expression was correlated with
      pathological differentiation and necrosis (P < 0.05). Survival analysis showed
      that patients with positive Ep-CAM or cyclin D1 expression had a shorter survival
      time than that in the patients without (P < 0.05). Moreover, Ep-CAM and cyclin D1
      expressions were positively correlated with each other (r = 0.307, P = 0.017).
      CONCLUSION: Ep-CAM or cyclin D1 expression is a unfavorable prognostic factor in
      gallbladder carcinoma.

PMID- 20137350
TI  - [Analysis of prognostic factors influencing the outcome of intrahepatic
      cholangiocarcinoma].
AB  - OBJECTIVE: To analyze the clinicopathologic factors influencing the outcome of
      surgically treated intrahepatic cholangiocarcinoma (ICC) and to explore the
      proper treatment choice of ICC. METHODS: The clinicopathological data of 43
      surgically treated ICC patients in our hospital were retrospectively analyzed. Of
      the 43 patients, hepatic resection was performed in 40 patients, ethanol
      injection in 2, and laparoscopic exploration alone in 1. Kaplan-Meier method and
      Cox regression model were used for the analysis of factors influencing survival
      after operation. RESULTS: The accumulative 1-, 3- and 5-year survival rates were
      64.4%, 30.9%, 25.8% for the whole group, and 74.7%, 33.3%, 27.8% for the 40
      patients with hepatic resection, respectively. Univariate analysis revealed that
      tumor size, carcinoembryonic antigen (CEA) level, lymph node involvement and TNM
      stage were factors significantly affecting the survival (P < 0.05). Cox
      multivariate analysis demonstrated that only tumor size and lymph node
      involvement were the independent factors significantly affecting the survival (P
      < 0.05). CONCLUSION: Our results show that tumor size and lymph node involvement
      are independent factors affecting the survival. CEA level and TNM stage are
      important prognostic factors for surgical management. Radical resection is still
      the optimal treatment for patient with intrahepatic cholangiocarcinoma.

PMID- 20137351
TI  - [Value of high-field MR diffusion-weighted MR imaging in the diagnosis of
      endometrial carcinoma].
AB  - OBJECTIVE: To investigate the usefulness of high-field MR diffusion-weighted
      imaging (DWI) in the diagnosis of endometrial carcinoma. METHODS: Thirty-five
      female patients with pathologically proven endometrial carcinoma, 10 patients
      with pathologically proven endometrial dysplasia and 41 normal volunteers were
      enrolled into this study. MR images were obtained at a 3.0 T MR scanner (GE,
      SIGNA EXCITE HD 3.0T) and an 8-element phased-array torsopa coil was used to
      receive MR signal. The conventional pulse sequences included axial SE T1WI, FSE
      T2WI and fat saturated FSE T2WI, sagittal FSE T2WI, and coronal fat saturated FSE
      T2WI. Axial DWI was performed in all patients using a SE-EPI sequence with a 1000
      s/mm(2) b value. The apparent diffusion coefficients (ADC) of carcinoma,
      dysplasia and normal mucosa were measured among the patients. RESULTS: Compared
      with myometrium, all the endometrial carcinoma, dysplasia and normal endometrium
      had a markedly high signal intensity on DWI. The ADC of endometrial carcinoma,
      dysplasia and normal endometrium was (1.08 +/- 0.23) x 10(-3)mm(2)/s, (1.29 +/-
      0.21) x 10(-3) mm(2)/s and (1.41 +/- 0.21) x 10(-3) mm(2)/s, respectively. There
      were statistically significant differences between the carcinoma and normal
      endometrium (t = -6.416, P = 0.000), and between the carcinoma and dysplasia (t =
      -2.590, P = 0.013). However, no significant difference in ADC was found between
      highly-differentiated and moderately-differentiated adenocarcinomas. CONCLUSION:
      High-field MR diffusion-weighted imaging (DWI) is highly sensitive in detecting
      endometrial lesions. It can be used to differentiate the endometrial carcinoma
      from either dysplasia or normal endometrium, but is difficult to differentiate
      highly-differentiated adenocarcinoma from moderately-differentiated one.

PMID- 20137352
TI  - [Diagnostic value of full-field digital mammography for breast carcinoma].
AB  - OBJECTIVE: To evaluate the diagnostic value of full-field digital mammography for
      breast cancer. METHODS: The clinical data and mammograms of 230 patients with
      breast diseases between January 2008 and July 2008 were collected and reviewed.
      Craniocaudal (CC) and mediolateral oblique (MLO) view mammograms were performed
      in all patients before surgery. Three experienced radiologists in breast imaging
      assessment analyzed and classified all the mammograms according to breast imaging
      reporting and data system (BI-RADS). The sensitivity, specificity and accuracy
      were evaluated according to their pathological diagnosis. The reasons resulting
      in false-negative and false-positive diagnosis were also analyzed. RESULTS: Of
      the 238 samples, 130 had a malignant breast tumors and 108 cases of benign breast
      lesions. One hundred and nine of the 130 malignant breast tumors were invasive
      ductal carcinoma. Fifty-seven of the 108 benign breast lesions were breast
      adenosis. Masses or masses with microcalcification were the most frequently seen
      signs of the malignant tumors, accounting for 40.8% and 20.8%, respectively. The
      sensitivity, specificity and accuracy of FFDM in detecting breast carcinoma were
      90.8%, 87.0% and 89.1%, respectively. The false-negative signs including negative
      X-ray finding (5 cases) and focal asymmetric densities (4 cases). The false
      positive signs were masses with spiculate, indistinctive or lobulated margin
      leading to misdiagnosing the lesions as malignant tumors. CONCLUSION: Full-field
      digital mammography (FFDM) is helpful in detection of breast cancers in women,
      with a higher sensitivity, specificity and accuracy, and has an important
      clinical application value.

PMID- 20137353
TI  - [Effect of neoadjuvant chemotherapy on histologic grade and expression of
      biological markers in breast cancer].
AB  - OBJECTIVE: The aim of this study is to investigate the changes of expression of
      estrogen receptors (ER), progesterone receptors (PR), Her-2, Ki-67 and
      histological grade after neoadjuvant chemotherapy in breast cancer. METHODS:
      Sixty-seven patients with histopathalogically confirmed breast cancer by core
      needle biopsy received neoadjuvant chemotherapy. The effect of neoadjuvant
      chemotherapy was assessed according to the criteria of the Japanese Breast Cancer
      Society: non-effective (G1), mildly effective (G2), moderately effective (G3),
      markedly effective (G4) and completely effective (G5). All pathological slides
      were retrospectively reviewed. Immunohistochemical staining (EnVision method) was
      used to detect the expression of ER and PR, Her-2 and Ki-67. The pre- and post
      neoadjuvant chemotherapy status of tumor histological grade, ER and PR, Her-2 and
      Ki-67 expression in the 49 cases were compared. RESULTS: The effect of
      neoadjuvant chemotherapy was assessed in 67 patients. There were 5 cases (7.5%)
      in G1, 19 in G2 (28.4%), 20 in G3 (29.9%), 17 in G4 (25.4%) and 6 in G5 (9.0%),
      respectively. PR positive rate was 71.4% after chemotherapy versus 91.8% before
      chemotherapy, with a statistically significant reduction (P = 0.021). However,
      the ER and Her-2 expression before and after neoadjuvant chemotherapy was stable.
      Of the patients with invasive ductal carcinoma, 28.6% had histological grade
      change after neoadjuvant chemotherapy, and 85.7% of patients decreased one grade.
      The proportion of histological grade change in the G1, G2, G3, G4 were 0, 5.9%,
      41.2% and 54.5%, respectively (P = 0.013). The average rate of Ki-67 expression
      decreased from 28.3% pre-chemotherapy to 11.0% post-chemotherapy (P = 0.011).
      After the neoadjuvant chemotherapy, the Ki-67 expression rate decreased by > 10%,
      > 20%, > 30%, > 40% and > 50% in 3 groups (G1 and G2, group G3, group G4 and G5)
      showed a tendency to be increased, with a significant difference (P < 0.05).
      CONCLUSION: PR expression in breast cancer decreases after neoadjuvant
      chemotherapy, while ER and Her-2 expressions remain stable. After neoadjuvant
      chemotherapy, the histological grade and proliferation index are decreased and
      correlated with the response to chemotherapy. Therefore, histological grade and
      proliferation index may be effective complementary factors in assessment of the
      effectiveness of neoadjuvant chemotherapy.

PMID- 20137354
TI  - [Postmastectomy radiotherapy in moderate-and high-risk elderly breast cancer
      patients].
AB  - OBJECTIVE: To analyze the role of postmastectomy radiotherapy (PMRT) in moderate-
      and high-risk elderly breast cancer patients. METHODS: The clinicopathological
      data of 874 breast cancer patients treated with mastectomy and axillary
      dissection were retrospectively analyzed. The T1-2N1 patients were defined as
      moderate- risk (IR) group, and T3-4 and/or N2-3 cases as high-risk (HR) group.
      The locoregional recurrence (LRR) and overall survival (OS) rates were calculated
      and compared according to different age groups and radiotherapy status. Kaplan
      Meier method and Log-rank test was used for calculation and comparison of the
      survival curves of different patient groups. RESULTS: The median follow up time
      was 47 months. 108 (12.4%) patients were > or = 65 years. For patients who were <
      65 and > or = 65 years, 18.1% and 15.3% received PMRT in the IR group, and 82.7%
      and 52.2% received PMRT in the HR group, respectively. For patients > or = 65
      years, the 5-year LRR rates were 0% and 14.2% (P = 0.242) and 5-year OS rates
      were 100% and 75.2% (P = 0.159) for the PMRT-IR and non-PMRT-IR groups,
      respectively. The 5-year LRR rates were 0% and 14.1% (P = 0.061), 5-year OS rates
      were 84.6% and 77.4% (P = 0.597) for the PMRT-HR and non-PMRT-HR groups,
      respectively. For patients < 65 years, the 5-year LRR rates were 0% and 9.9% (P =
      0.035) and 5-year OS rates were 87.0% and 82.1% (P = 0.739) for the PMRT-IR and
      non-PMRT-groups, respectively. The 5-year LRR rates were 7.2% and 26.1% (P =
      0.000), 5-year OS rates were 79.2% and 57.7% (P = 0.000) for the PMRT-HR and non
      PMRT-HR groups, respectively. CONCLUSION: With the increasing of age, there is a
      trend of decreasing use of postmastectomy radiotherapy in high-risk breast cancer
      patients. Postmastectomy radiotherapy can improve the locoregional control for
      high-risk patients and maybe considered even for those who are > or = 65 years.

PMID- 20137355
TI  - [Analysis of responses and prognostic factors in different chemotherapy regimens
      for metastatic nasopharyngeal carcinoma: a report of 171 cases].
AB  - OBJECTIVE: The aim of this study was to compare the results of different combined
      chemotherapy regimens and to find the best regimen for metastatic nasopharyngeal
      carcinoma (NPC), and determine its prognostic factors. METHODS: The clinical data
      of 171 patients with pathologically proven metastatic NPC were retrospectively
      analyzed. Of them, 26 were treated with best support care (BSC group), 92 with
      platinum-based regimen of two drugs (FP group: 5-Fu and cisplatin; TP group:
      paclitaxel and cisplatin; DP group: docetaxel and cisplatin), and 53 with
      platinum-based regimen of three-drugs (TFP group: FP plus paclitaxel, DFP group:
      FP plus doxtale). RESULTS: The response rate (RR) in the three-drug regimens was
      significantly higher than that in the two-drug regimen (84.9% vs. 52.2%, P =
      0.000), however, grade III approximately IV myelosuppression in the three-drug
      regimen group was also significantly higher than that in the two-drug regimen
      (58.5% vs. 27.2%, P = 0.000). Among the groups treated with platinum-based
      combination regimens of either two drugs or three drugs, no significant
      differences were observed in RR (P = 0.967, P = 0.400) or median survival time
      (MST) (P = 0.278, P = 0.413). The MST and one-year survival rate were 4.0 months,
      13.2 months and 15.0 months, 24.0%, 64.1% and 70.3% in the BSC group, two-drug
      group and three-drug group, respectively. The MST in the chemotherapy group was
      significantly longer than that in BSC group (P = 0.000). Cox multivariate
      regression analysis showed that Karnovsky performance scores, time to progression
      or chemotherapy cycles were independent prognostic factors (P < 0.05).
      CONCLUSION: Chemotherapy can improve the survival of metastatic NPC. Platinum
      based combination regimen with two drugs is still the standard treatment. The
      combination regimens with three drugs can increase the RR, but no survival
      benefit can be achieved for its high toxicity.

PMID- 20137356
TI  - [Surgical treatment and prognosis of cancer of hepatic flexure of colon invading
      the duodenum in 65 patients].
AB  - OBJECTIVE: To discuss surgical treatment of right colon carcinoma of hepatic
      flexure invading the duodenum. METHODS: Sixty-five patients with right colon
      carcinoma of hepatic flexure invading the duodenum, treated in our department
      from 1987 to 2007, were included in this study. Their clinicopathological data
      were retrospectively reviewed and analyzed. All the cases were divided into three
      types (local invasion, regional invasion, and cancer with internal fistula)
      according to duodenal defect, including local invasion (< 2.0 cm), wide invasion
      (> 2.0 cm) and the presence of internal fistula. RESULTS: 25 patients with local
      invasion underwent en bloc resection of the duodenal wall. Pedicled ileal flap
      was used to cover the large duodenal defect measuring 2.0 - 3.0 cm in 5 patients.
      Dudenojejunostomy was used to reconstruct the large defect measuring more than 5
      cm in 3 patients. Conservative resection of right-sided colon was performed in 18
      patients with wide invasion. 4 patients underwent pancreaticoduodenectomy
      combined with right hemicolectomy for colon cancer involving the pancreatic head.
      10 underwent duodenal diverticularization. One patient with anastomotic leakage
      healed within 3 weeks. Other patients were cured without postoperative
      complications. The total 3-year and 5-year survival rates after surgery were
      53.8% and 9.2%, respectively. CONCLUSION: The surgical procedure to be performed
      is usually decided according to the cancer location, extent, and duodenal defect
      and invasion, which are important for prolonging life time, improving of quality
      of life and prognosis in these patients.

PMID- 20137357
TI  - [From head and neck surgery to head and neck oncology: the disciplinary guarantee
      for comprehensive cancer therapy].

PMID- 20137358
TI  - Prognostic analysis of patients with gastrointestinal stromal tumors: a single
      unit experience with surgical treatment of primary disease.
AB  - BACKGROUND: Gastrointestinal stromal tumor (GIST), the most common type of
      mesenchymal tumors of the gastrointestinal tract, is a recently recognized tumor.
      The biological behavior of GIST is highly variable. Surgical resection remains
      the major treatment for GIST. In this study we retrospectively analyzed our
      surgical experience with 181 GIST patients to determine the effects of the
      treatment and the pathological features and prognosis factors of these GIST
      patients. METHODS: The clinicopathological features and follow-up data of the 181
      patients with GIST who had received surgical resection between January 1999 and
      December 2007 at Ren Ji Hospital were retrospectively reviewed.
      Immunohistochemical stains including CD117 (KIT), CD34, and other markers were
      used. Tumor size, mitotic index and other pathological parameters were recorded.
      According to the consensus of NIH risk-group stratification system based on
      maximum tumor size and mitotic index (per 50 high power field), tumors were
      classified into very-low-risk group (15 tumors, 8.3%), low-risk group (48,
      26.5%), intermediate-risk group (52, 28.7%) and high-risk group (66, 36.5%).
      Prognostic factors were analyzed by Cox analysis including age, sex, tumor size,
      tumor site, mitotic index, NIH categories and surgical procedures. RESULTS: One
      hundred and seven (59.1%) of the 181 tumors were located in the stomach, 51
      (28.2%) in the small intestine, 9 (5.0%) in the colon and rectum, and 14 (7.7%)
      in other sites including the omentum and mesentery. The median age of the
      patients was 58 (range, 24-84) years, and 102 patients (56.4%) were male. Tumor
      size ranged from 0.5 to 30 cm, while the mean size was 7.02 cm. Metastasis was
      found in 7 patients. One hundred and seventy-six (97.2%) of the 181 patients
      underwent radical resection, and among them 26 patients received extensive
      resection with the adjacent organ adherent to the tumors. The positive rate for
      the KIT protein (CD117) in immunostaining was 94.5% (171/181), while that for
      CD34 was 86.2% (156/181). The 1-, 3-, and 5-year survival rates of the 181
      patients were estimated to be 95.2%, 87.9% and 78.5%, respectively. There was a
      significant difference in age, tumor size, tumor site, mitotic index, NIH
      categories, and presence or absence of multivisceral resection (P<0.05). But
      there was no significant difference in sex between the groups. Cox hazard
      proportional model revealed that advanced clinical stage and large tumor size
      contributed to worse prognosis. The patients who were treated with imatinib
      because of recurrence and metastasis or high recurrence risk showed stable
      disease. CONCLUSIONS: Surgical resection is the gold standard of treatment for
      primary GIST. NIH categorization is simple and effective to evaluate GIST
      behavior and prognosis. Targeted therapy such as imatinib, a KIT tyrosine kinase
      inhibitor, may play an important role in the treatment of GIST.

PMID- 20137359
TI  - Long-term outcomes of choledochoduodenostomy for hepatolithiasis.
AB  - BACKGROUND: Oddi sphincter plays an important role in preventing reflux
      cholangitis. There exists the controversy on application of
      choledochoduodenostomy in hepatolithiasis management. The present study aimed at
      evaluating long-term outcomes of choledochoduodenostomy for the treatment of
      hepatolithiasis. METHODS: Forty-six consecutive cases of hepatolithiasis who
      underwent choledochoduodenostomy were analyzed retrospectively. The pre- and
      postoperative rates of recurrent cholangitis and acute cholangitis severe type
      were compared. Paired chi-square test was applied. RESULTS: The mean follow-up
      time was 17.3 years ranging from 1.6 to 40 years with a follow-up rate of 97.8%
      (45/46). High rates of remnant stones (39.1%, 18/46), recurrent stones (31.1%,
      14/45), uncorrected strictures (85%, 17/20), and mortality (24.4%, 11/45) were
      observed in this group. Regurgitation of food debris and duodenal content into
      the biliary tract through the anastomosis was observed. The rate of recurrent
      cholangitis was equal to the preoperative period (93.3%, 42/45). The rate of
      acute cholangitis severe type after choledochoduodenostomy (46.7%, 21/45)
      increased significantly (P<0.01) when compared to the preoperative period (20.0%,
      9/45). CONCLUSIONS: Choledochoduodenostomy did not entirely achieve the goal of
      clearance of stones, correction of strictures, and removing of hepatobiliary
      lesions by itself. Choledochoduodenostomy without cholangioplasty resulted in an
      increase of severe reflux cholangitis due to the loss of the anti-reflux function
      of the sphincter of Oddi. Therefore, choledochoduodenostomy is not an ideal
      approach to reduce cholangitis in hepatolithiasis and is not the best choice in
      the management of hepatolithiasis.

PMID- 20137360
TI  - Relief of abdominal pain by morphine without altering physical signs in acute
      appendicitis.
AB  - BACKGROUND: Abdominal pain is a common symptom among patients with acute
      appendicitis, yet these patients have long been denied relief from suffering
      because of widespread misconceptions associated with the use of opioids. We
      determined whether morphine hydrochloride masked the physical signs in adults
      with acute appendicitis and assessed the efficacy of morphine in relieving
      abdominal pain. METHODS: A prospective, double-blind, placebo controlled,
      clinical trial was conducted with 106 adult patients between 16 and 70 years old
      with acute appendicitis. Patients were randomly divided into a morphine group
      (n=54) or a normal saline group (n=52). All patients presented with acute
      abdominal pain with onset within 3 days. The morphine group received hypodermic
      injection of morphine (0.15 mg/kg; maximum 20 mg) and the control group members
      were given an equivalent volume of normal saline solution. The clinical symptoms,
      physical signs, and patients' cooperation during physical examination were
      assessed before and after 30 minutes of morphine or normal saline administration.
      RESULTS: Abdominal pain was significantly relieved and the patients' cooperation
      was improved in the morphine group after 30 minutes treatment compared with the
      control group and before morphine administration (P<0.05). The physical signs
      were unaffected by either treatment (P>0.05). CONCLUSIONS: Morphine relieved
      abdominal pain and improved the patients' cooperation for treatment and care.
      Furthermore, the morphine did not mask the physical signs of acute appendicitis.

PMID- 20137361
TI  - Three-dimensional reconstruction of digitized human liver: based on Chinese
      Visible Human.
AB  - BACKGROUND: Comparing with two dimensional (2D) imaging, both in diagnosis and
      treatment, three dimensional (3D) imaging has many advantages in clinical
      medicine. 3D reconstruction makes the target easier to identify and reveals the
      volume and shape of the organ much better than 2D imaging. A 3D digitized visible
      model of the liver was built to provide anatomical structure for planing of
      hepatic operation and for realizing accurate simulation of the liver on the
      computer. METHODS: Transverse sections of abdomen were chosen from the Chinese
      Visible Human dataset. And Amira software was selected to segment and reconstruct
      the structures of the liver. The liver was reconstructed in three-dimensions with
      both surface and volume rendering reconstruction. RESULTS: Accurately segmented
      images of the main structures of the liver were completed. The reconstructed
      structures can be displayed singly, in small groups or as a whole and can be
      continuously rotated in 3D space at different velocities. CONCLUSIONS: The
      reconstructed liver is realistic, which demonstrates the natural shape and exact
      position of liver structures. It provides an accurate model for the automated
      segmentation algorithmic study and a digitized anatomical mode of viewing the
      liver.

PMID- 20137362
TI  - Primary effect of dual growing rod technique for the treatment of severe
      scoliosis in young children.
AB  - BACKGROUND: Treatment of rapidly progressing scoliosis in young children is a
      challenge for spine surgeons. Some surgeons had begun to use dual growing rod
      technique for treatment of rapidly progressing scoliosis in young children and
      had achieved acceptable results. The aim of this study was to determine the
      primary results and complications of this new technique in China. METHODS: Eleven
      children suffering from rapidly progressing scoliosis were treated with dual
      growing rod technique between November 2004 and March 2009 at Peking Union
      Medical College Hospital (PUMCH). There were 10 females and 1 male in the group
      with Risser sign of 0 grade. The mean age at initial surgery was 6.1 years
      (range, 2.1-10.9 years). Ten patients were diagnosed as congenital scoliosis and
      1 patient neuromuscular scoliosis. All the patients had 1-4 lengthening
      procedures (mean, 1.8 procedures) after the initial surgeries. The radiographic
      results of all the patients were investigated. RESULTS: The coronal Cobb angle of
      scoliosis improved from (67.64+/-11.43) degrees to (34.64+/-8.26) degrees after
      initial surgery with the correction rate observed at (47.15+/-16.48)%. The
      coronal trunk shift improved from (2.00+/-1.73) cm to (1.49+/-1.31) cm after
      initial surgery. The T1-S1 height increased from (25.47+/-6.16) cm to (28.84+/
      5.69) cm after initial surgery. The coronal Cobb angle of scoliosis was (36.82+/
      11.76) degrees and the coronal trunk shift was (1.11+/-1.29) cm after the most
      recent lengthening procedure with the most recent correction rate observed at
      (44.73+/-19.43)%. The T1-S1 height was (31.29+/-4.50) cm after the most recent
      lengthening procedure with an average T1-S1 length increase of 1.6 (range, 1.0
      2.7) cm per year during the lengthening period. The sagittal balance was
      maintained. Five of the total patients (45.5%) had complications including: hook
      displacement, pedical screw loosening, and broken rod. We performed revision
      surgeries with simultaneous lengthening procedures in all 5 cases with
      satisfactory results. CONCLUSIONS: The dual growing rod technique was useful in
      the management of rapidly progressing scoliosis in young children. This technique
      could control severe scoliosis, allow for spinal growth, and maintain the coronal
      and sagittal balance. But the technique has high complications requiring strict
      and regular follow-up.

PMID- 20137363
TI  - Total hip arthroplasty for patients with osteoarthritis secondary to hip pyogenic
      infection.
AB  - BACKGROUND: Pyogenic hip arthritis occurs most often in young patients. Delayed
      treatment causes significant anatomical deformation of bony and soft tissue
      structures leading to premature onset of secondary osteoarthritis. Total hip
      arthroplasty (THA) in patients who had osteoarthritis secondary to hip pyogenic
      infection has been associated with high complication rates. METHODS: We analyzed
      19 THAs performed from April 2003 to July 2008 in adults with osteoarthritis
      secondary to hip pyogenic infection (average age 40.7 years; range 34-52 years).
      There were 7 males and 12 females, the average age of infection was 10.6 years
      (range 7-13 years) and the average quiescent period of infection was 29.5 years
      (range 22-41 years). The count of white blood cell (WBC), erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP) were examined routinely
      before surgery. The duration of followup was 34 months (range 6-52 months).
      RESULTS: There was no evidence of infection according to laboratory values,
      intraoperative exploration and bacterial culture of joint fluids and synovial
      tissues. Split fracture above the lesser trochanter occurred in two hips and
      healed without adverse sequelae after fixation with wires. One patient with
      sciatic nerve palsy was successfully treated by positioning the hip in extension
      and the knee in flexion with complete resolution of motor symptoms one month
      later. There were no cases of dislocation, deep vein thrombosis, or postoperative
      reinfection. The symptoms and hip joint activities were significantly improved.
      The median Harris hip score improved from 47.3 preoperatively to 89.7 and the
      median range of motion from 53 degrees to 125 degrees. CONCLUSIONS: It is safe
      and efficient to perform THA in patients who had osteoarthritis secondary to
      pyogenic hip arthritis when the infection is quiescent. The key points of
      successful surgery are exclusion of active infection preoperatively, quiescent
      period of infection more than ten years and adequate intraoperative soft tissue
      releases.

PMID- 20137364
TI  - Cruciate ligament reconstruction using LARS artificial ligament under
      arthroscopy: 81 cases report.
AB  - BACKGROUND: There are many different materials used for ligament reconstruction.
      Currently, autograft, allograft, and artificial ligaments are used in the
      reconstruction. The objective of this study was to explore the clinical result of
      cruciate ligament reconstruction under arthroscopy. METHODS: Eighty-one cases
      were reconstructed with the LARS ligament under arthroscopy, including 43 cases
      of anterior cruciate ligament (ACL) injury, 20 cases of posterior cruciate
      ligament (PCL) injury, and 18 cases of ACL combined with PCL injuries of the
      knee. The follow up period was 10 to 49 months. The International Knee
      Documentation Committee (IKDC) and Lysholm knee score scales were used for
      functional evaluation. We examined the anterior and posterior stability of the
      knee with KT-1000. RESULTS: According to the Lysholm knee function score scale,
      the average preoperative score of (44.6+/-1.4) increased to a postoperative score
      of (82.8+/-2.5) in the ACL group and from (46.6+/-2.3) to (80.8+/-2.0) in the PCL
      group. In the ACL combined with PCL injury group, the preoperative score
      increased from (45.2+/-1.2) to (85.5+/-2.3). According to IKDC score standards,
      in ACL group we evaluated 19 cases as C and 24 cases as D, preoperatively, and
      postoperatively 27 cases as A, 14 cases as B and two cases as C. In the
      preoperative PCL group, we had 11 cases defined as C and nine cases as D that
      resolved to 12 cases as A, seven as B and one case of C in postoperative
      evaluation. In the ACL combined with PCL injury group we defined four cases as C
      and 14 as D during preoperative scoring. These patients had postoperative grades
      of six cases as A, 10 as B, and two cases as C. All of the results have
      statistical significance. CONCLUSIONS: ACL, PCL, or combined ACL and PCL
      reconstruction using the LARS ligament under arthroscopy is a minimally invasive,
      safe and effective method to treat cruciate ligament injuries of the knee.
      Clinical results are satisfactory in the short term.

PMID- 20137365
TI  - Immediate effects of acupuncture on gait patterns in patients with knee
      osteoarthritis.
AB  - BACKGROUND: Acupuncture has been shown to be effective in pain relief and
      anesthesia, and has been suggested for treating various kinds of functional
      disabilities in traditional Chinese medicine, including knee osteoarthritis (OA).
      The study aimed to investigate the immediate effects of acupuncture on gait
      patterns in patients with knee OA. METHODS: Twenty patients with bilateral medial
      knee OA were assigned evenly and randomly to a sham group and an experimental
      group. During the experiment, the experimental group underwent a 30-minute
      formula electro-acupuncture treatment while the sham group received a sham
      treatment. Before and after treatment, each subject was evaluated for their knee
      pain using visual analog scales (VAS) and then their performance of level walking
      using gait analysis. For all the obtained variables, the independent t-test was
      used for between-group comparisons, while paired t-test was used to investigate
      the before and after changes. RESULTS: All the measured data before acupuncture
      treatment between the groups were not significantly different. The VAS scores
      were decreased significantly after acupuncture in both groups, and the mean
      change of the VAS values of the experiment group was 2 times greater than that of
      the sham group. After formula acupuncture stimulation, while no significant
      changes were found in all the gait variables in the sham group, the experimental
      group had significant increases in the gait speed, step length, as well as in
      several components of the joint angles and moments. CONCLUSIONS: The results of
      the study suggest that significantly improved gait performance in the
      experimental group may be associated with pain relief after treatment, but the
      relatively small decrease of pain in the sham group was not enough to induce
      significant improvements in gait patterns. Gait analysis combined with the VAS
      can be useful for the evaluation of the effect of acupuncture treatment for
      patients with neuromusculoskeletal diseases and movement disorder.

PMID- 20137366
TI  - Comparison of bupivacaine, ropivacaine and levobupivacaine with sufentanil for
      patient-controlled epidural analgesia during labor: a randomized clinical trial.
AB  - BACKGROUND: Ropivacaine and levobupivacaine have been introduced into obstetric
      analgesic practice with the proposed advantages of causing less motor block and
      toxicity compared with bupivacaine. However, it is still controversial whether
      both anesthetics are associated with any clinical benefit relative to bupivacaine
      for labor analgesia. This study aimed to compare the analgesic efficacy, motor
      block and side effects of bupivacaine, ropivacaine and levobupivacaine at lower
      concentrations for patient-controlled epidural labor analgesia. METHODS: Four
      hundred and fifty nulliparous parturients were enrolled in this randomized
      clinical trial. A concentration of 0.05%, 0.075%, 0.1%, 0.125% or 0.15% of either
      bupivacaine (Group B), ropivacaine (Group R) or levobupivacaine (Group L) with
      sufentanil 0.5 microg/ml was epidurally administered by patient-controlled
      analgesia mode. Effective analgesia was defined as a visual analogue scale score
      was <or=30 mm. The relative median potency for each local anesthetic was
      calculated using a probit regression model. Parturients demographics, sensory and
      motor blockade, obstetric data, maternal side effects, hourly volumes of local
      anesthetic used, and others were also noted. RESULTS: There were no significant
      differences among groups in the numbers of effective analgesia, pain scores,
      hourly local anesthetic amount used, sensory and motor blockade, labor duration
      and mode of delivery, side effects and maternal satisfaction (P>0.05). The
      relative median potency was bupivacaine/ropivacaine: 0.828 (0.602-1.091),
      bupivacaine/levobupivacaine: 0.845 (0.617-1.12), ropivacaine/levobupivacaine:
      1.021 (0.774-1.354), respectively. However, a significantly less number of
      effective analgesia and higher hourly local anesthetic use were observed in the
      concentration of 0.05% than those of >or=0.1% within each group (P<0.05).
      CONCLUSIONS: Using patient-controlled epidural analgesia, lower concentrations of
      bupivacaine, ropivacaine and levobupivacaine with sufentanil produce similar
      analgesia and motor block and safety for labor analgesia. The analgesic efficacy
      mainly depends on the concentration rather than the type of anesthetics.

PMID- 20137367
TI  - Nontuberculous mycobacteria: susceptibility pattern and prevalence rate in
      Shanghai from 2005 to 2008.
AB  - BACKGROUND: An increasing incidence of disease caused by nontuberculous
      mycobacteria (NTM) is being reported. The purpose of this study was to determine
      the isolation rates of NTM from various clinical specimens, and their
      antimicrobial susceptibility patterns, over a 4-year period in Shanghai. METHODS:
      All NTM isolated between 2005 and 2008 at Shanghai Pulmonary Hospital, a key
      laboratory of mycobacteria tuberculosis in Shanghai, China, were identified with
      conventional biochemical tests and 16S rRNA gene sequencing. Antimicrobial
      susceptibility for all NTM was determined using the BACTEC MGIT 960 system.
      RESULTS: A total of 21,221 specimens were cultured, of which 4868 (22.94%) grew
      acid fast bacilli (AFB), and 248 (5.09%) of the AFB were NTM. The prevalence rate
      of NTM was determined as 4.26%, 4.70%, 4.96% and 6.38% among mycobacteria culture
      positive samples in years 2005, 2006, 2007 and 2008 respectively. These data
      indicated that the prevalence rate has continuously increased. Sixteen different
      species of NTM were identified, the most commonly encountered NTM in Shanghai
      were M. chelonae (26.7%), followed by M. fortuitum (15.4%), M. kansasii (14.2%),
      M. avium-intracellulare complex (13.1%) and M. terrae (6.9%). The rare species
      identified were M. marinum, M. gastri, M. triviale, M. ulcerans, M. smegmatis, M.
      phlci, M. gordonae, M. szulgai, M. simiae, M. scrofulaceum and M. xenopi. The
      five most commonly identified NTM species showed high drug resistance to general
      anti-tuberculosis drugs, particularly, M. chelonae and M. fortuitum appear to be
      multi-drug resistance. CONCLUSIONS: The prevalence of NTM in Shanghai showed a
      tendency to increase over the course of the study. The five most commonly
      isolated NTM species showed high drug resistance to first line anti-tuberculosis
      drugs.

PMID- 20137368
TI  - Atrial natriuretic peptide gene polymorphism is not associated with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary autosomal dominant
      inheritant myocardial disease with heterogeneity in clinical manifestations,
      natural history and prognosis. Even carrying an identical gene mutation among
      family members, a variety of clinical phenotypes have been found in patients with
      HCM. Modifier genes may contribute to the diversity. The plasma levels of atrial
      natriuretic peptides (ANP) were found previously to be elevated in HCM. Our
      studies suggested that ANP gene promoter polymorphism is associated with left
      ventricular hypertrophy in hypertension. The present study aimed to determine
      whether the two SNPs in the ANP gene are associated with HCM. METHODS: We
      determined the relationships between the ANP gene polymorphism and HCM in 262 HCM
      patients and 614 age- and sex-matched healthy individuals. All of the subjects
      were genotyped for -A2843G and A188G polymorphisms. RESULTS: The genotype
      frequency in the -A2843G and A188G polymorphisms of the ANP gene was not
      significantly different between the HCM patients and controls. The -A2843G and
      A188G polymorphisms were also not associated with clinical phenotype in
      cardiomyopathy patients. CONCLUSIONS: The polymorphisms of the ANP gene are not
      associated with increasing risk of HCM or clinical phenotypes. The variations of
      the ANP gene may not serve as a genetic modifier for the development of HCM.

PMID- 20137369
TI  - Relationship between serum vasoactive factors and plaque morphology in patients
      with non-ST-segment elevated acute coronary syndrome.
AB  - BACKGROUND: Vasoactive factors have been reported to correlate with vulnerable
      plaque and acute coronary syndrome (ACS). This study aimed to investigate the
      relationship between vasoactive factors and plaque morphology in patients
      suffering from non-ST-segment elevated ACS. METHODS: From April 2007 to April
      2009, 124 consecutive patients suffering from non-ST-segment elevated ACS who had
      received coronary angiography (CAG) and intravascular ultrasound (IVUS) in the
      People's Liberation Army General Hospital and Beijing Anzhen Hospital were
      enrolled in this study. Three serum vasoactive factors, plasma soluble vascular
      endothelial growth factor receptor-1 (sFlt-1), placental growth factor (PLGF) and
      interleukin-18 (IL-18), were measured by enzyme-linked-immunosorbent serologic
      assay of the patients. The levels of vasoactive factors were compared between
      vulnerable plaque group and stable plaque group, and between unstable angina
      pectoris (UAP) group and non-ST-segment elevation acute myocardial infarction
      (NSTE-AMI) group. The relationship between the plaque morphology and levels of
      vasoactive factors was analyzed. RESULTS: The levels of vasoactive factors were
      similar between the UAP group (69 patients) and NSTE-AMI group (55 patients). The
      levels of sFlt-1 and PLGF in the vulnerable plaque group were significantly
      higher than those in the stable plaque group. The level of IL-18 was correlated
      positively with plaque morphology. Multivariate Logistic regression analysis
      showed that the level of PLGF was an independent risk factor for vulnerable
      plaque (OR=2.115, 95% CI 1.415-5.758, P=0.018). Using the ROC curve, PLGF was a
      significant factor for the diagnosis of vulnerable plaque (the diagnostic point
      was 26.3 ng/L, the proportion of square area under the ROC curve was 0.799, 95%CI
      0.758-0.839, P<0.001; the sensitivity of PLGF under the ROC curve was 86%, and
      the specificity 63%). CONCLUSION: Both IL-18 and PLGF are biomarkers for
      vulnerable plaques and helpful to predict vulnerable plaque.

PMID- 20137370
TI  - Fcgamma receptor IIIA polymorphisms and efficacy of rituximab therapy on Chinese
      diffuse large B-cell lymphoma.
AB  - BACKGROUND: Rituximab is used extensively in combination with chemotherapy to
      cure non-Hodgkin's lymphoma (NHL), and not only accelerates short-term
      improvement, but also prolongs patient survival and decreases receptor relapse.
      The aim of this study was to evaluate the impact of Fcgamma IIIA (FcgammaRIIIA)
      gene polymorphisms on the response to rituximab therapy for newly diagnosed B
      cell lymphomas. METHODS: Patients with newly diagnosed histologically-proven CD20
      positive B-cell lymphoma were eligible for the study. All of the patients
      received rituximab combined with chemotherapy (CHOP). The FcgammaRIIIA type was
      analyzed by PCR. The initial efficacy was assessed after 6 cycles and the long
      term survival was determined. RESULTS: Thirty-four patients were recruited
      between October 2005 and April 2006. The FcgammaRIIIA distribution was as
      follows: 11 patients were VV, 5 were FF, and 18 were VF. After a median of 6
      cycles (range 4-8) of rituximab combined chemotherapy, the overall response rate
      was 79% (82% in the VV group, 83% in the VF group, and 60% in the FF group;
      P=0.04). After a median follow-up time of 37 months (range 34-41), there were 12
      relapses among 27 responders (44%); 5 of 9 patients (5/9) in the VV group, 5 of
      15 patients (33%) in the VF group, and 2 of 3 patients (2/3) in the FF group
      (P=0.21). The 1-year overall survival in the VV, FF, and VF groups was 80%, 60%,
      and 80%, respectively, and the 3-year overall survival was 58%, 40%, and 69%,
      respectively (P=0.08). After analysis by COX regression, only the international
      prognosis index and response to initial treatment were significantly related to
      overall survival. CONCLUSIONS: The distribution of FcgammaRIIIA polymorphisms in
      this B-cell lymphoma population shows that VF is most frequently expressed,
      followed by VV and FF. Patients with the FcgammaRIIIA VV and VF types are more
      sensitive to the initial treatment of rituximab combined with chemotherapy and
      have superior long-term survival compared with those with FF. Nevertheless,
      FcgammaRIIIA polymorphisms do not predict prognosis independently.

PMID- 20137371
TI  - Measurement of anterior chamber volume with rotating scheimpflug camera and
      anterior segment optical coherence tomography.
AB  - BACKGROUND: Measurement of anterior segment parameters plays an important role in
      diagnosis and treatment of glaucoma. The objective of this study was to evaluate
      the repeatability and reproducibility of anterior chamber volume (ACV)
      measurements with rotating scheimpflug camera (RSC) and to examine agreement with
      anterior segment optical coherence tomography (AS-OCT). METHODS: Thirty nine
      healthy normal subjects were recruited from the Eye Center of Tongren Hospital.
      ACV was measured using RSC and AS-OCT in a randomly selected eye for each
      subject. For RSC measurements, both automatic and manual ACV measurements and 2
      independent operators' ACV measurements were obtained. All subjects were invited
      for 3 visits within a week to evaluate repeatability and reproducibility of ACV
      measurement by RSC. Agreement was evaluated between RSC and AS-OCT. RESULTS: Good
      repeatability and reproducibility were found for both automatic and manual ACV
      measurements obtained by RSC. For intrasession repeatability, coefficient of
      variation (CVw) and intraclass correlation coefficient (ICC) values for automatic
      were 3.52% and 0.98; the values for manual were 3.44% and 0.97, respectively. For
      intersession reproducibility, the respective CVw and ICC values were 3.96% and
      0.96. Good agreement was also found in 2 operators for both automatic and manual
      ACV measurements; nevertheless, poor agreement was found between RSC and AS-OCT
      (95% confidence interval (CI) for agreement of automatic RSC measurement versus
      AS-OCT were -96.3 to 72.8 microl and 95% CI for agreement of manual RSC
      measurement versus AS-OCT were between -41.7 to 10.1 microl). CONCLUSIONS: Both
      RSC automatic and manual ACV measurements showed good repeatability and
      reproducibility, and showed comparable agreement between 2 independent operators,
      but poor agreement was found between RSC and AS-OCT.

PMID- 20137372
TI  - Influence of galvano-ceramic and metal-ceramic crowns on magnetic resonance
      imaging.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is prone to be deformed by artifacts
      caused by the presence of metallic materials. The aim of this study was to
      evaluate the artifacts from galvano-ceramic and metal-ceramic crowns in MRI, in
      order to analyze their influences on diagnostic interpretation of MRI. METHODS:
      Galvano-ceramic and metal-ceramic crowns (Bio98, Wiron99, SP-78, BioKC97) were
      fabricated with the same model. All materials were imaged by means of 1.5T MRI
      apparatus with three different sequences, T1-weighted spin-echo (T1-weighted SE),
      T2-weighted spin-echo (T2-weighted SE) and Gradient echo (GE). Mean and standard
      deviation of distilled water signal intensity (SI) around the sample in the
      region of interest (500 mm2) enclosing the whole artifacts were determined, and
      compared for evaluation of the homogeneity of signal intensity. Images around the
      sample were acquired and evaluated. RESULTS: There were statistically significant
      differences in the values of signal intensity between acrylic resin control and
      BioKC97, Wiron99 in the three sequences (P<0.001). The mean values of signal
      intensity for Bio98, SP-78 were significantly different from that of acrylic
      resin control (RE) in GE sequence (P<0.001). No difference was showed between
      acrylic resin control and galvano-ceramic crown (P>0.05). Images showed that the
      greatest artifact was a 25 mm ring with distortion in Wiron99 in GE sequence.
      CONCLUSIONS: This in vitro study suggested that galvano-ceramic crown had no
      influence on the MRI, while metal-ceramic crowns caused moderate artifacts in the
      MRI. Therefore, galvano-ceramic restoration is a valuable alternative in
      dentistry.

PMID- 20137373
TI  - Blockade of 4-1BB/4-1BB ligand interactions prevents acute rejection in rat liver
      transplantation.
AB  - BACKGROUND: Blocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the
      secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play
      a key role in organ transplantation tolerance. The aim of this study was to
      investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with
      4-1BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver
      transplantation. METHODS: The orthotopic liver transplantation model was set up,
      while male Lewis rats were used as liver donors and Brown-Norway rats as
      recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB
      or isotype control antibody. Groups were monitored for graft survival after
      transplantation. Plasma chemistry, including aspartate transaminase (AST),
      alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The
      concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)-gamma in plasma
      were also measured by enzyme-linked immunosorbent assay. Allograft histology
      images were collected under light microscope and electron microscope. RESULTS:
      Isotype antibody treated recipients exhibited elevated plasma levels of liver
      injury markers including AST, ALT and BIL, progressive portal and venous
      inflammation and cellular infiltration of the liver allografts, and a mean graft
      survival time (MST) of 10.9 days. Administration of anti 4-1BBL mAB resulted in a
      decrease in plasma levels of liver injury markers and the concentrations of IL-2,
      IL-10 and IFN-gamma. The histological grade of rejection on day 7 decreased and
      MST (17.3 days) increased substantially. CONCLUSIONS: These results demonstrate
      that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co
      stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a
      promising strategy to prevent progression of graft rejection by suppressing T
      cell-mediated immunity.

PMID- 20137374
TI  - Differential effect of three mitogen-activated protein kinases on lipoprotein (a)
      induced human mesangial cell proliferation.
AB  - BACKGROUND: Mesangial hypercellularity is a critical early histopathological
      finding in human and experimental glomerular diseases. Hyperlipidemia and the
      glomerular deposition of lipoproteins are commonly associated with mesangial
      hypercellularity and play an important pathobiological role in the development of
      glomerular diseases. The activated cytoplasmic mitogen-activated protein kinase
      (MAPK), including mainly extracellular-signal regulated protein kinase (ERK), c
      Jun amino-terminal kinase (JNK), and p38, has been thought to translocate into
      the nucleus and activate various transcription factors and protooncogenes
      associated with cell growth and proliferation. Lipoprotein (a) (Lp(a)) has been
      shown to stimulate proliferation of mesangial cells, but the events of Lp(a)
      signaling have not yet been characterized. The purpose of this study was to
      investigate the signal transduction pathways involved in Lp(a)-induced cell
      proliferation and provide an evidence for the participation of Lp(a) in
      intracellular signaling pathways for mesangial cell proliferation. METHODS: Lp(a)
      was isolated from a patient who was being treated with low density lipoprotein
      (LDL)-apheresis by density gradient ultracentrifugation and then chromatography.
      Human mesangial cells (HMCs) were isolated by the sequential sieving technique
      and stimulated with Lp(a) in different concentration and time course. The DNA
      synthesis of the cells was measured by [3H] thymidine incorporation for detecting
      the proliferation. The expression of all the three members of MAPK family,
      including ERK1/ERK2, JNK, and p38, and their phosphorylation were detected by
      Western blotting. RESULTS: Lp(a) could induce a significant dose-dependent
      proliferation of HMCs. The 3H-TdR incorporation was 1.64+/-0.31, 1.69+/-0.48,
      3.59+/-0.68 (P<0.01), 4.14+/-0.78 (P<0.01), and 4.05+/-0.55 (P<0.01) (10(3) cpm)
      at the Lp(a) concentration of 0, 5, 10, 25, and 50 microg/ml, respectively. Lp(a)
      induced an increase in ERK1/ERK2 phosphorylation between 5 and 60 minutes, and in
      JNK phosphorylation between 15 and 30 minutes after incubating with HMCs, whereas
      the level of p38 and its phosphorylation was not changed. CONCLUSIONS: Lp(a)
      could stimulate the proliferation of HMCs by activiating the phosphorylation of
      ERK1/ERK2 and JNK MAPK signaling pathway, whereas p38 pathway had no effect on
      the Lp(a)-induced HMC proliferation, which indicated that three MAPKs seem to be
      distinctly involved in the effect. In particular, it also provides the evidence
      that Lp(a) may act as one of the major endogenous modulators for mitogenic
      signaling response and cell proliferation within the glomerulus.

PMID- 20137375
TI  - Exchange of a nuclear corepressor between NF-kappaB and CREB mediates inhibition
      of phosphoenolpyruvate carboxykinase transcription by NF-kappaB.
AB  - BACKGROUND: NF-kappaB p65 was shown to inhibit transcription of
      phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in
      gluconeogenesis in the liver. To understand the mechanism of action of NF-kappaB
      p65, we investigated the nuclear receptor corepressor in the regulation of PEPCK
      transcription. METHODS: Rat H4IIE cells, human hepatoma HepG2 cells and human
      embryo kidney (HEK) 293 cells were used in this study. The transcriptional
      activity of a rat PEPCK gene promoter (-490/+100) was analyzed in HepG2 cells, a
      HepG2 super suppressor IkBalpha (ssIkBalpha) stable cell line, and HEK 293 cells.
      The effects of p65 and ssIkBalpha on a rat PEPCK gene promoter were observed
      using the PEPCK luciferase reporter system. The interaction of the cAMP-response-
      element-binding (CREB) protein, histone deacetylase 3 (HDAC3) and silencing
      mediator for retinoic and thyroid hormone receptors (SMRT) with the PEPCK gene
      promoter were investigated using the chromatin immunoprecipitation (ChIP) assay.
      p65 cotransfection and RNAi-mediated gene knockdown were used to determine the
      corepressor involved in the inhibition of PEPCK by NF-kappaB p65 and the
      transcriptional regulation of CREB by NF-kappaB p65. RESULTS: NF-kappaB p65
      inhibited PEPCK expression and the inhibition was blocked by ssIkBalpha. The
      inhibitory effect of p65 was completely blocked in a HepG2 stable cell line in
      which ssIkBalpha was expressed. HDAC3 or SMRT knockdown led to a significant up
      regulation of PEPCK reporter activity in the presence of p65 cotransfection. In
      the ChIP assay the interaction of HDAC3 and SMRT with the PEPCK gene promoter was
      induced by p65 activation, but the CREB signal was reduced. Transcriptional
      activity of CREB was inhibited by NF-kappaB p65 cotransfection. The inhibitory
      effect of NF-kappaB p65 was blocked by HDAC3 RNAi or SMRT RNAi. CONCLUSIONS: The
      study showed that the inhibition of PEPCK by NF-kappaB p65 was dependent on HDAC3
      and SMRT, which form a nuclear corepressor complex for transcriptional
      inhibition. The transcription factors NF-kappaB p65 and CREB share the same
      corepressor HDAC3-SMRT, and the corepressor exchange leads to inhibition of PEPCK
      gene transcription by NF-kappaB p65.

PMID- 20137376
TI  - Alteration of cholinergic and peptidergic neurotransmitters in rat ileum induced
      by acute stress following transient intestinal infection is mast cell dependent.
AB  - BACKGROUND: Mast cells are implicated in the development of irritable bowel
      syndrome (IBS), which is associated with the activation of the "neural-immune"
      system. The aim of this study was to investigate the role of mast cells in the
      remodeling of cholinergic and peptidergic neurotransmitters induced by acute cold
      restriction stress (ACRS) post infection (PI) using mast cell deficient rats
      (Ws/Ws) and their wild-type controls (+/+). METHODS: Transient intestinal
      infection was initiated by giving 1500 Trichinella spiralis (T.S.) larvae by
      gavage. ACRS was induced for 2 hours at day 100 PI. Samples of terminal ilea were
      prepared for H&E staining, mast cell counting and activation and assessment of IL
      1beta and IL-10. RESULTS: When infected, both strains of rats experienced an
      acute infectious stage followed by a recovery. Histological scores were
      significantly higher in infected rats compared with those of the non-infected
      controls at day 10 PI (10 day-PI vs. control: +/+: 2.75+/-0.17 vs. 0.42+/-0.09;
      Ws/Ws: 2.67+/-0.67 vs. 0.50+/-0.34; P<0.01). In +/+ rats, post-infection ACRS
      induced the formation of low-grade inflammation, represented by the imbalance of
      IL-1beta and IL-10 (IL-1beta: PI+ACRS vs. control: (1812.24+/-561.61) vs.
      (1275.97+/-410.21) pg/g, P<0.05; IL-10: PI+ACRS vs. control: (251.9+/-39.8) vs.
      (255.3+/-24.7) pg/g, P>0.05), accompanied by hyperplasia and activation of mast
      cells (PI+ACRS vs. control: 58.8+/-19.2 vs. 28.0+/-7.6; P<0.01). The balance
      between acetylcholine (ACh) and substance P (SP) was also disturbed (ACh: PI+ACRS
      vs. control: (743.94+/-238.72) vs. (1065.68+/-256.46) pg/g, P<0.05; SP: PI+ACRS
      vs. control: (892.60+/-231.12) vs. (696.61+/-148.61) pg/g, P<0.05). Nevertheless,
      similar changes of IL-1beta/IL-10 and ACh/SP were not detected in Ws/Ws rats.
      CONCLUSION: The imbalance of ACh/SP, together with the activation of mucosal
      immunity induced by post-infection ACRS were lacking in mast cell deficient rats,
      which supports the premise that mast cells play an important role in cholinergic
      and peptidergic remodeling in the ileum of rats.

PMID- 20137377
TI  - Efficacy and safety of tamsulosin for the treatment of benign prostatic
      hyperplasia: a meta analysis.
AB  - BACKGROUND: Pharmacological therapy has been considered as the first-line
      treatment for patients with uncomplicated benign prostatic hyperplasia (BPH). The
      aim of this study was to evaluate the efficacy and safety of tamsulosin compared
      with a placebo for treating BPH. METHODS: The randomized placebo-controlled
      trials (RCT) of tamsulosin for the treatment of BPH from all over the world were
      searched. PubMed, Ovid, ScienceDirect, EBSCO, CBM, and CNKI were searched, as
      well as a manual search of four Chinese journals: Chinese Journal of Andrology,
      National Journal of Andrology, Chinese Journal of Urology, and Journal of
      Clinical Urology was also performed. Two reviewers independently screened the
      studies for eligibility, evaluated the quality and extracted the data from the
      eligible studies, with confirmation by cross-checking. Divergences of opinions
      were settled by discussion. Meta-analysis was processed by Rev Man 5.0 software,
      fail-safe number was performed by SAS8.0 software. RESULTS: Seven RCTs involving
      2455 men met the inclusion criteria. The basic characteristics of patients were
      comparable in all the studies. Comparing three common criteria: international
      prostate symptom score (IPSS)/Boyarsky symptom score, maximum flow rate (MFR),
      quality of life (QOL), tamsulosin was better than placebo at improving IPSS and
      MFR, with no significant difference in the QOL. Adverse events of tamsulosin also
      showed no significant difference from the placebo group (Z=1.62, P=0.10, OR=1.22,
      95% CI 0.96-1.54). CONCLUSIONS: Tamsulosin is better than placebo at improving
      IPSS and MFR. Adverse events of tamsuloisn show no significant difference
      compared with placebo. More high quality trials with larger samples and longer
      follow-up are proposed.

PMID- 20137378
TI  - Association between intervertebral disc degeneration and disturbances of blood
      supply to the vertebrae.

PMID- 20137379
TI  - Natural orifice translumenal endoscopic surgery (NOTES): current status and
      challenges.
AB  - OBJECTIVE: To give a conceptual description of natural orifice translumenal
      endoscopic surgery (NOTES), review the early efforts in the NOTES field, and
      discuss its challenges and limitations. DATA SOURCES: The data were retrieved
      mainly from publications listed in MEDLINE, PubMed and China Wanfang Database
      from 2005 to 2009. The search term was "NOTES". STUDY SELECTION: The articles
      involved in the "NOTES" study were selected and the review articles were excluded
      from the comparison. RESULTS: A marked increase in quantity in articles was shown
      each year for NOTES studies from 2006 to 2009. Animal experiments with "NOTES"
      have been carried out in China from 2007, and two independent "NOTES" procedures
      on humans were reported in 2009. CONCLUSION: Although still in its infancy, the
      "NOTES" procedure is promising as another type of minimally invasive surgery and
      favorable alternative to current interventions.

PMID- 20137380
TI  - Incomplete spondylolysis of the first sacrum: a case report.

PMID- 20137381
TI  - Adult primary undifferentiated embryonal sarcoma of the liver: a case report.

PMID- 20137382
TI  - Prevention of tumor emboli from the inferior vena cava by the Tempofilter II
      during resection of nephroblastoma with level III tumor thrombus.

PMID- 20137384
TI  - Time for the new approach in management of early phase of severe acute
      pancreatitis?

PMID- 20137385
TI  - [Experimental research on biological responses of productive dusts from pottery
      factories and tungsten mines].
AB  - OBJECTIVE: To assess biological response and health adverse effects of industrial
      dusts from pottery factories and tungsten mines on alveolar macrophages (AM) in
      vitro. METHODS: AM acquired from bronchoalveolar lavage of guinea pigs were used
      as the target cells. AM were then co-cultured with respirable dust particles (15,
      30, 60 and 120 MUg/106) from pottery factories and tungsten mines. LDH activity,
      cell viability, the release of ROS and TNF-alpha were determined to assess the
      biological responses of the dusts. China Standard Quartz was used as control.
      RESULTS: Dose- response relationships between the dust concentrations and the
      enhancement of LDH activity, the release of ROS and TNF-alpha were found in both
      dusts from pottery factories and tungsten mines. The cell viability decreased
      when the dusts' concentrations increased. Differences of biological response were
      observed in the dust particles from different mines or factories. Compared with
      the pottery dusts, higher LDH activity and the release of TNF-alpha induced by
      tungsten dust were observed. In the 120 MUg/106 group, the TNF-alpha induced by
      tungsten dust, pottery dusts and China Standard Quartz was (5.2 +/- 2.0) ng/ml,
      (3.3 +/- 1.6) ng/ml and (2.8 +/- 0.5) ng/ml respectively. However, the impact on
      the cell viability induced by pottery dust was higher than that by tungsten mine.
      CONCLUSION: Industrial dusts from various sources could induce different
      biological effects. The results of the biological effects of dusts in laboratory
      tests may be of potential use to provide base data for their adverse effects
      evaluation.

PMID- 20137386
TI  - [Effect of down-regulated hOGG1 gene expression on cytotoxicity and genotoxicity
      of hydroquinone].
AB  - OBJECTIVE: To explore the effects of down- regulated hOGG1 gene expression on
      cytotoxicity and genotoxicity of hydroquinone. METHODS: A549 cells and A549-R
      cells with down- regulated hOGG1 gene were treated with different concentrations
      of hydroquinone (0, 5, 10, 20, 40 and 80 MUmol/L). The cellular sensitivity and
      contents of ROS were measured by MTT assay and fluorescence method, respectively.
      The chromosome damage was measured by micronucleus test. The DNA damage and
      repair were examined using comet assay in both cells. RESULTS: The cell viability
      decreased with increasing concentration of hydroquinone. The IC50 of hydroquinone
      was 160.49 and 228.42 MUmol/L in hOGG1 deficient A549-R cell and in A549 cell
      respectively (P < 0.05). When the dose of hydroquinone reached 5 micromol/L and
      above, the contents of ROS and the rate of micronucleated cells in A549-R cells
      were significantly higher than in A549 (P < 0.05) cells. At the same time, the
      comet rate and OTM in A549-R cells were significantly higher compared with A549
      cells at 5 micromol/L and above in a dose-response way (P < 0.05). Furthermore,
      in DNA repair assay, A549-R cells with down- regulated hOGG1 gene were more
      difficult to repair than A549 cells. In A549-R cells, the comet rate and OTM
      reduced significantly until after 2 h repair time and even after 3 h the DNA
      damage was not repaired completely. CONCLUSION: Oxidative damage may be one of
      the toxicological mechanisms of hydroquinone, and hOGG1 deficiency could increase
      sensitivity of A549-R cells to hydroquinone.

PMID- 20137387
TI  - [Association between CYP2B6, CYP2D6, GSTP1 genetic polymorphisms and urinary
      styrene metabolites in professional workers].
AB  - OBJECTIVE: To evaluate the influence of individual genetic polymorphisms of
      metabolic enzymes on urinary styrene metabolites. METHODS: 58 workers
      occupationally exposed to styrene were divided into the high exposure group (>=
      100 mg/m3) and the low exposure group (< 100 mg/m3). The microfluidic chip
      technology was used to determine the SNPs of CYP2B6, CYP2D6 and GSTP1 and the
      influence of gene polymorphisms on the metabolism of styrene was statistically
      analyzed. RESULTS: The level of urine styrene metabolites level was influenced by
      genotypes of CYP2B6, CYP2D6 and GSTP1 [(280.28 +/- 100.60) mg/g Cr vs (183.48 +/-
      127.52) mg/g Cr, (233.04 +/- 77.56) mg/g Cr vs (152.46 +/- 95.47) mg/g Cr, (32.88
      +/- 7.14) mg/g Cr vs (24.47 +/- 5.59) mg/g Cr, P < 0.05)]. The metabolism of
      CYP2B6 G/G homozygotic genotype to styrene was more active than G/T heterozygotic
      genotype and T/T mutation genotype. The level of PHEMA in GSTP1 homozygotic
      genotype subjects was significantly higher than that in the group of homozygotic
      genotype [(32.07 +/- 7.32) mg/g Cr vs (25.59 +/- 6.95) mg/g Cr, P < 0.05)]. The
      influence of CYP2D6 genotypes on urinary metabolites was also observed in the
      same study [(56.36 +/- 109.72) mg/g Cr vs (177.13 +/- 116.21) mg/g Cr, (118.73 +/
      84.55) mg/g Cr vs (148.48 +/- 99.83) mg/g Cr, (18.29 +/- 13.50) mg/g Cr vs
      (19.95 +/- 13.30) mg/g Cr, P < 0.05)]. CONCLUSION: Genotypes of CYP2B6, GSTP1 and
      CYP2D6 are related to susceptibility to the metabolism of styrene in human.

PMID- 20137388
TI  - [Effect of deltamethrin on production of free radical and transcription factor
      Nrf2 in rats' brain tissue].
AB  - OBJECTIVE: To explore the effect of deltamethrin (DM) on production of free
      radical and transcription factor Nrf2 in rats' brain tissue. METHODS: 8 male rats
      were randomly assigned to four groups and administered with 1% W/W tertiary
      butylhydroquinone (tBHQ) or olive oil for 3 days, prior to exposure to DM and
      then with 12.50 mg or 0mg DM/Kg BW for 5 days. The level of free radical in rats'
      hippocampus tissue was detected by electron spin resonance (ESR) spectroscopy. 18
      male rats were randomly assigned to three groups and administered with i.p.
      (daily dose was respectively 0, 3.13, 12.50 mg/kg DM) for five days. After
      treatment, Nrf2 protein levels in the cytoplasmic and nuclear fractions of both
      cerebral cortex and hippocampus tissue were measured by western blot. RESULTS:
      The level of free radical in hippocampus tissue of rats administered by DM and
      pretreatment with tBHQ prior to DM were increased to a 2.45-fold and 2.97-fold of
      values of control group, respectively (P < 0.05). Nrf2 protein levels in the
      cytoplasmic fractions of cerebral cortex of both low and high dose group were
      significantly increased, 1.68- fold and 1.34- fold of values of control group,
      respectively. Nrf2 protein levels in the nuclear fractions of cerebral cortex of
      both low and high dose group were increased in a dose- dependent model, 1.51-fold
      and 2.29-fold of values of control group, respectively (P < 0.01). Nrf2 protein
      levels in the cytoplasmic fractions of hippocampus tissue of both low and high
      dose group were increased in a dose- dependent model, 2.26-fold and 3.58-fold of
      values of control group, respectively. Nrf2 protein levels in the nuclear
      fractions of hippocampus tissue of both low and high dose group were increased,
      2.42-fold and 2.45-fold of values of control group, respectively (P < 0.01).
      CONCLUSION: The studies in vivo demonstrate that DM treatment could induce free
      radical production and expression of Nrf2 protein in both cerebral cortex and
      hippocampus tissue and activate Nrf2.

PMID- 20137389
TI  - [Protective effect of tert-butylhydroquinone on PC12 cells from neurotoxicity
      induced by manganese in vitro].
AB  - OBJECTIVE: To investigate the protective effect of the tert-butylhydroquinone
      (tBHQ) on PC12 cells from neurotoxicity induced by manganese. METHODS:
      Cytotoxicity of PC12 cells was measured by MTT assay, following the PC12 cells
      treatment with different concentrations of MnCl2 (300, 600, 900 MUmol/L) for 24,
      48 or 72 h. PC12 cells were pretreated with 40 MUmol/L tBHQ for 12 h, followed by
      the treatment of 600 micromol/L or 300 MUmol/L MnCl2 for 72 h. Cytotoxicity of
      PC12 cells was measured by MTT assay, and cell apoptosis was examined by the
      method of Annexin V-FITC/PI in flow cytometry (FCM). RESULTS: The proliferation
      of PC12 cells treated with 300, 600, 900 MUmol/L MnCl2 was suppressed in the dose
      dependent pattern (P < 0.01). Proliferation of PC12 cells treated with 600
      MUmol/L MnCl2 was suppressed to 40% of that in control group (P < 0.01), but the
      proliferation rate of PC12 cell pretreated with 40 MUmol/L tBHQ was 180% of that
      in control group (P < 0.01). Apoptotic rate of PC12 cells treated with 300
      micromol/L MnCl2 was higher than the vehicle control group (P < 0.01). Apoptotic
      rate of 40 MUmol/L tBHQ pretreatment followed by 300 MUmol/L MnCl2 treatment was
      lower than that of MnCl2 treatment group (P < 0.01). The inhibition rate of
      apoptosis was 61%. CONCLUSIONS: Manganese may suppress PC12 cells proliferation
      and induce apoptosis. tBHQ can reduce PC12 cells proliferation suppressed by
      manganese and attenuate the apoptosis induced by manganese.

PMID- 20137390
TI  - [Immunotoxic effect of herbicide simazine exposure in BALB/c mice].
AB  - OBJECTIVE: To examine the effect of simazine on selected immune parameters in
      BALB/c mice. METHODS: Simazine (90, 200, 400 mg/kg) was administrered by oral
      gavage for 21 days in adult BALB/c mice. The negative control group unith
      distilled water and positive control group administered with cyclophosphamide in
      abdominal cavity were also established. After the last simazine dose, the mice
      were sacrificed, and blood, spleens, and thymuses were collected and processed
      for detection. The relative weight of spleen and thymus was calculated. The rate
      of T cell in spleen and the concentration of IL-2, IL-4, IgG and IgM were
      detected by ELISA. RESULTS: The weights of mice were decreased in 200 mg/kg and
      400 mg/kg simazine groups. Thymus and spleen weights were decreased in 200 mg/kg
      and 400 mg/kg simazine groups compared with the negative control group. The
      concentration of IL-2, IL-4, IgG and IgM in serum of 200 mg/kg group were (108.50
      +/- 3.20) pg/ml, (36.54 +/- 3.36) pg/ml, (46.25 +/- 7.41) MUg/ml, (17.58 +/-
      2.23) MUg/ml respectively;The concentration of IL-2, IL-4, IgG and IgM in serum
      of 400 mg/kg group were (85.70 +/- 4.00) pg/ml, (35.92 +/- 2.29) pg/ml, (40.08 +/
      6.80) MUg/ml, (11.92 +/- 3.23) MUg/ml respectively (P < 0.05 or P < 0.01). These
      results were decreased significantly compared with negative group. CONCLUSION:
      Simazine can inhibit the cellular immune function and the humoral immune
      function.

PMID- 20137391
TI  - [Precise liver resection-new concept of liver surgery in 21st century].

PMID- 20137392
TI  - [Personal experience in precise hepatectomy guided by the concept of minimally
      invasive surgery].

PMID- 20137393
TI  - [Clinical application of precise liver resection techniques in patients with
      complicated liver space-occupying lesions].
AB  - OBJECTIVE: To evaluate the early results of precise liver resection. METHODS:
      Between May 2006 and June 2009, 65 patients with complicated liver space
      occupying lesions were included in the study. Fifty-one patients underwent
      curative liver resection. Liver resections performed included 16
      trisectionectomies, 11 hemihepatectomy, 5 meso hepatectomies, 3 combined
      segmentectomies, 5 caudate lobectomies and 11 irregular local resections.
      RESULTS: Patients undergoing resection had no mortality with a major morbidity of
      9.8%. Nineteen vascular repairs and reconstructions were patent at last follow
      up. The postoperative 1-year survival rate was 100% in 10 patients with benign
      lesions and 92.7% in 41 patients with malignant tumors. The 1-year survival rate
      was zero in patients with malignant tumors, who underwent no liver resection.
      CONCLUSIONS: Precise liver resection, as an aggressive surgical approach, offers
      hope for these patients, who would otherwise have a dismal prognosis.

PMID- 20137394
TI  - [Surgical technique and concept in precise hepatectomy: experience of 338 cases
      of hepatectomy in single center].
AB  - OBJECTIVE: To evaluate the perioperative clinical outcome and predictive factors
      for perioperative complication morbidity and mortality. METHODS: From August 2003
      to August 2008, the data of 338 cases of hepatectomy performed in the liver
      transplant center of the First Affiliated Hospital of Nanjing Medical University
      was collected in a prospective manner. The patients' perioperative clinical risk
      factors and results were analyzed. RESULTS: In the 338 hepatectomy cases, 255
      patients (75.4%) underwent precise anatomical hepatectomy. The overall
      perioperative complication morbidity was 18.1%, while the perioperative mortality
      was 0.6%. In a total of 211 (62.4%) cases, the operation was carried out without
      blood transfusion. Univariate analysis revealed that cirrhotic liver,
      thrombocytopenia, blood loss in operation > 1000 ml, blood transfusion in
      operation and several other factors were closely related with the incidence rate
      of complication. Multivariate logistic regression analysis indicated that
      thrombocytopenia and perioperative blood transfusion were important independently
      predictive factors for the occurrence of perioperative complications in
      hepatectomy. CONCLUSIONS: Precise hepatectomy enables patients to obtain better
      clinical outcome with low complication morbidity and perioperative mortality.
      Reducing hemorrhage is an important factor that lead to good clinical results.

PMID- 20137395
TI  - [Development and clinical application of 3D operative planning system of live in
      virtual reality environments].
AB  - OBJECTIVE: To explore and develop three-dimension (3D) virtual reality (VR) liver
      model and convert computed tomography data into a fully 3D VR environment for
      display, measure and manipulation. METHODS: 3D-reconstruction of liver was
      restored from spiral computed tomography (CT) data by using LiVirtue software.
      Dextrobeam was used to view the 3D model in the VR environment. The liver and its
      anatomic structure were reconstructed to illuminate the location of the tumor and
      its related vessels. RESULTS: 3D models of liver, tumor and their relative
      vessels were reconstructed successfully. These models could be viewed and
      manipulated in the VR environment on personal computer.38 patients underwent
      liver resection, including 21 right hemihepatectomy, 14 left hemihepatectomy and
      3 extended right hemihepatectomy. The intraoperative contrast with preoperative
      simulation confirmed the reliability of our 3D operative planning system.
      CONCLUSIONS: The preoperative simulation in 3D VR facilitated liver resection by
      the ability to view tumor and its relative vessels. This preoperative estimation
      from 3D model of liver benefits a lot to complicated liver resection.

PMID- 20137396
TI  - [The role of full length superior mesenteric artery isolation in extended
      pancreaticoduodenectomy in the treatment of ductal adenocarcinoma of the pancreas
      in the uncinate process].
AB  - OBJECTIVE: To improve the prognosis and safety of extended
      pancreaticoduodenectomy for patients with pancreatic cancer in the uncinate
      process of pancreas. METHODS: From January 2004 to March 2008, 26 extended
      pancreaticoduodenectomies with full length superior mesenteric artery (SMA)
      isolation and mesentery root resection were performed for the ductal
      adenocarcinomas in the uncinate process of pancreas. There were 16 males and 10
      females aging from 30 to 75 years old [medium age (55.0 +/- 13.0) years old].
      Eleven of 26 patients were combined with portal vein-superior mesenteric vein
      resection. The effect and safety of this procedure were analyzed retrospectively.
      RESULTS: There was no operative mortality in all patients. The pathological
      examination showed that all the incisal margins were negative. After a follow-up
      of 7 to 45 months, the pain relief was occurred in all patients. The 1-year, 2
      year accumulated survival rates were 72.2%, and 48.1%, respectively. CONCLUSIONS:
      Full length SMA isolation and the mesentery resection in extended
      pancreaticoduodenectomy are safe and effective. The procedure is also benefit for
      the patients in improving the survival rate and quality of life.

PMID- 20137397
TI  - [Effect of neoadjuvant chemoradiotherapy on the healing of anastomosis following
      low anterior resection in locally advanced rectal cancer].
AB  - OBJECTIVE: To investigate the effect of the neoadjuvant chemoradiotherapy (NCR)
      on the healing of anastomosis following low anterior resection in patients with
      locally advanced rectal cancer. METHODS: Between May 2001 and August 2007, 192
      patients with T3 and T4 low rectal cancer (distance from the tumor to anal verge
      </= 6 cm) enrolled in the study. All patients were subjected to preoperative
      radiotherapy to pelvis, with a total dose of 40 - 46 Gy in 20 days fractions of 2
      Gy each in 4 weeks and simultaneously combined with oral capecitabine (CAP) of
      1250 mg/m(2) bid continuously for 10 weeks up to surgery. The patients were
      operated on 6 weeks after the end of radiotherapy according to the rule of TME
      technique. RESULTS: All patients fulfilled the study. Of the patients, 17 cases
      were diagnosed tumor free after the neoadjuvant therapy and were not operated on.
      Other 24 cases were found got complete tumor response with pathological
      examination after the operation. A total of 41 cases (21.4%) got complete tumor
      response with the neoadjuvant therapy. Surgery was performed in 175 patients, and
      166 patients (95.3%) with sphincter-saving resection, 134 patients with low
      anterior resection (LAR, double stapling technique) and 32 patients with Park's
      endoanal anastomosis. Six patients were operated with abdomino-perineal resection
      (APR) and 3 patients with Hartmann's procedure. Anastomotic leakage was found in
      9 patients (5.1%), 6 patients (4 cases of rectovaginal leakage) with LAR(double
      stapling technique) and 3 patients (1 case of rectovaginal leakage) with Parks
      technique (P > 0.05). Anastomotic leakage occurred in 2 - 10 days post operation,
      and were managed properly and got desirable results. CONCLUSION: Neoadjuvant
      chemoradiotherapy would not affect the healing of anastomosis obviously if being
      applied reasonably in locally advanced low rectal cancer.

PMID- 20137398
TI  - [Evaluation of neoadjuvant chemotherapy for patients with stage II osteosarcoma].
AB  - OBJECTIVE: To retrospectively review the effect of chemotherapy and survival rate
      of osteosarcoma in extremity. METHODS: Between July 1997 and July 2007, 296
      patients with osteosarcoma received neo-adjuvant chemotherapy and surgery. There
      were 184 males and 112 females, with age between 7 and 65 years. The tumors
      located in proximal femur in 10 patients, diaphyseal of femur in 7, distal femur
      in 148, proximal tibia in 80, distal tibia in 5, fibula in 11, humerus in 33, and
      distal radius in 2 patients. According to Enneking stage system, 6 patients were
      in stage IIA and others in stage IIB. All patients received evaluation of
      preoperative chemotherapy, and 72 patients had analysis of tumor necrosis after
      operation. RESULTS: After mean follow-up of 47 months, metastasis developed in 98
      (33.1%) patients. The metastatic rate was 15.5%, 31.0%, and 77.1% in patients
      with substantial effective chemotherapy, partial effective chemotherapy, and no
      effective chemotherapy, respectively. In tumor necrosis analysis, reduction of
      tumor volume and more clear margin after preoperative chemotherapy were related
      to higher tumor necrosis. CONCLUSIONS: The patients with osteosarcoma should
      receive chemotherapy as soon as possible. More effective chemotherapy means lower
      metastatic rate and higher no event survival rate.

PMID- 20137399
TI  - [Decreased circulating matrilin-1 levels in adolescent idiopathic scoliosis].
AB  - OBJECTIVE: To determine the circulating matrilin-1 levels in adolescent
      idiopathic scoliosis (AIS), and to investigate its potential role in
      etiopathogenisis of AIS. METHODS: This study population consisted of 25 patients
      with AIS from June 2006 to March 2007 and 25 age-matched normal controls. All
      subjects of the study met the following criteria: no evidence of bone diseases,
      metabolic diseases or growth disturbances; no evidence of systemic illness or
      other condition known to affect bone metabolism; and no history of recent steroid
      intake and surgery of congenital cardiopathy. The maximum Cobb angle and curve
      pattern of AIS group were recorded. All AIS patients were categorized by
      progressive and non-progressive groups. Progression to a severe curve was defined
      per usual clinical criteria (progression to a > 40 degrees curve in an individual
      still growing or progression to a > 50 degrees curve in an adult). Measurements
      of genotype by PCR-RFLP methods and circulating matrilin-1 by ELISA assay were
      performed in both AIS and control groups. The circulating matrilin-1 levels were
      compared between AIS and control groups, and also among different genotype
      individuals. The relationship between matrilin-1 levels and cure progression were
      also analyzed. RESULTS: Compared with control group, a marked decrease of plasma
      matrilin-1 levels was found in AIS groups (P = 0.0002). Matrilin-1 levels of both
      AIS and control groups with GG genotype tended to be lower than with AA and AG
      genotypes, and this trend was stronger in AIS groups. Compared with non
      progressive AIS group, plasma matrilin-1 levels in progressive AIS group were
      significantly lower. CONCLUSIONS: There is an association between matrilin-1
      levels and curve progression. Measurement of circulating matrilin-1 levels is
      helpful for early screening and diagnosis of AIS, and it may be considered as an
      independent index to predict curve progression.

PMID- 20137400
TI  - [Unilateral versus bilateral balloon kyphoplasty in the treatment of multi
      vertebral osteoporotic compression fractures].
AB  - OBJECTIVE: To comparatively study the efficacy and safety of unilateral and
      bilateral balloon kyphoplasty in the treatment of painful multi-vertebral
      osteoporotic compression fractures. METHODS: From May 2002 to June 2007, 41
      consecutive patients with painful multi-vertebral osteoporotic compression
      fractures underwent unilateral or bilateral kyphoplasty. The unilateral group
      included 3 male and 14 female with an average age of 70.4 (range 52 to 91 years
      old). The bilateral group included 4 men and 20 women with an average age of 72.4
      (range 61 to 87 years old). Each procedure included insertion of inflatable
      balloon, fracture reduction and cement filling under "C"-arm monitoring.
      Preoperative and postoperative pain level, SF-36 score, radiographs and
      complications were recorded and analyzed. RESULTS: All 41 patients tolerated the
      operation well. The mean operation time were (86 +/- 32) min and (120 +/- 26) min
      for unilateral and bilateral groups respectively; the mean volume of cement
      injected into one level were (3.9 +/- 1.6) ml and (5.4 +/- 2.1) ml for unilateral
      and bilateral groups respectively. The mean follow-up were (32.5 +/- 17.2) months
      and (30.7 +/- 14.3) months for unilateral and bilateral groups respectively. The
      mean VAS pain score of unilateral group decreased significantly from 7.4 +/- 2.1
      preoperatively to 2.7 +/- 1.9 postoperatively (t = 2.50, P < 0.05) and 3.1 +/-
      2.2 at final follow-up, the mean VAS pain score of bilateral group decreased
      significantly from 7.9 +/- 2.1 preoperatively to 2.3 +/- 2.5 postoperatively (t =
      2.41, P < 0.05) and 2.7 +/- 2.2 at final follow-up, no significant difference was
      found between two groups. Significant increase of the mean height of anterior and
      medial vertebral body were recorded after the operation and maintained at final
      follow-up. The mean correction of local kyphosis was 7.2 degrees +/- 4.9 degrees
      for unilateral group and 7.3 degrees +/- 5.9 degrees for bilateral group, no
      significant difference was found between two groups. Postoperatively, 6 of 8
      subscales measured by SF-36 were significantly improved for both groups.
      Complications were found in 7 patients including 6 cases of cement leakage and 1
      case of pulmonary embolization. CONCLUSION: As a minimally invasive procedure,
      unilateral or bilateral kyphoplasty is effective and relatively safe for multi
      vertebral osteoporotic compression fracture.

PMID- 20137401
TI  - [Kinematics of the triangular fibrocartilage complex during forearm rotation in
      vivo].
AB  - OBJECTIVE: To investigate three-dimensional kinematics of the superficial and
      deep portion of triangular fibrocartilage complex (TFCC) in different parts of
      the forearm rotation. METHODS: Six wrists of 6 volunteers were used to obtain CT
      scans at different positions of the wrist. The wrists were scanned from 90
      degrees of pronation to 90 degrees of supination at an interval of 30 degrees.
      The 3-dimensional radius and ulna were reconstructed with customized software and
      changes in length of the superficial and deep portion of TFCC during forearm
      rotation. RESULTS: In forearm pronation, the superficial dorsal portion and the
      deep palmar portion of the TFCC were tight. While the superficial palmar portion
      and the deep dorsal potion of the TFCC were lax. In supination, the changes in
      length of all these fibers were reverse. CONCLUSIONS: In forearm rotation one
      portion fibers of dorsal TFCC and one portion fibers of palmar TFCC are tight,
      and this mechanism controls stability during DRUJ rotation.

PMID- 20137402
TI  - [Comparison of three different methods of anesthesia during transrectal
      ultrasound guided prostate biopsy: a prospective, double-blind, randomized
      trial.].
AB  - OBJECTIVE: To assess the clinical efficacy and safety of three different methods
      of anesthesia during transrectal ultrasound guided prostate biopsy. METHODS: From
      July 2006 to October 2008, a total of 120 patients who underwent 12-core prostate
      biopsy with transrectal ultrasound guidance because of elevated prostate specific
      antigen and/or abnormal digital rectal examination were randomized into 4 groups,
      each group consisted of 30 patients. Group A received no anesthesia. Group B
      received an injection of 10 ml dose of 1% lidocaine (5 ml per side) into the
      region of the prostatic vascular pedicle at the prostate base just lateral to the
      junction between the seminal vesicle and prostate on each side for periprostatic
      nerve block (PNB). Group C received intrarectal lidocaine gel plus PNB. Group D
      received an injection of 4 ml dose of 1% lidocaine (2 ml per side) into 2 sites
      of the right and left sides of prostate for intraprostatic anesthesia plus PNB.
      The efficiency of anesthesia was assessed by a visual analog pain scale (VAS).
      All patients were followed up within one week for the evaluation of
      complications. RESULTS: The combination of intraprostatic anesthesia and PNB
      provided significantly better pain control than PNB alone. According to VAS, only
      group C (2.7 +/- 1.1) scores showed significantly better pain control than other
      groups (P < 0.05) during probe insertion, and only group D (3.9 +/- 1.3) scores
      showed significantly better pain control than other groups (P < 0.05) during
      biopsy. No difference was observed regarding the complications rate in the 4
      groups (P > 0.05). CONCLUSIONS: Combination of intraprostatic anesthesia and PNB
      is effective and safe technique during transrectal ultrasound guided prostate
      biopsy without increasing the incidence of complications. PNB or PNB plus
      intrarectal lidocaine gel couldn't significantly reduce pain during biopsy.

PMID- 20137403
TI  - [The expression of chemokine-like factor 1 in human atherosclerotic plaques].
AB  - OBJECTIVE: To evaluate the difference of the expression level of chemokine-like
      factor 1 (CKLF1) mRNA and protein between human atherosclerotic plaques and
      normal arteries. METHODS: Real-time quantitative PCR was performed with
      experimental group (24 cases of atherosclerotic plaques) specimens and control
      group (25 cases of normal arteries) specimens. Serial microscopic sections were
      used for immunohistochemistry with CKLF1 antibody in 17 experimental group
      specimens and 10 control group specimens. RESULTS: The endothelial cell, vascular
      smooth muscle cell (VSMC) and macrophage were CKLF1 positive expression cells in
      atherosclerotic plaques. There was a foundational expression of CKLF1 mRNA in
      control group (RQ(Median) = 2.4), and the expression of CKLF1 mRNA in
      experimental group is up-regulated significantly (RQ(Median) = 132.2, P < 0.05).
      The VSMC positive expression rate of CKLF1 protein was 100% in experimental group
      and 70% in control group, the former was up-regulated significantly. CONCLUSIONS:
      The expression of CKLF1 is up-regulated in atherosclerotic plaques. It may play
      an important role in the process of immune and inflammatory responses of
      atherogenesis.

PMID- 20137404
TI  - [Total body irradiation of the donor in a spontaneous tolerance rat liver
      transplantation model and the effects on CD4(+)CD25(+) regulatory T cells
      content].
AB  - OBJECTIVE: To study the effect of total body irradiation of the donor in a
      spontaneous tolerance rat liver transplantation model and the role of
      CD4(+)CD25(+) regulatory T cells on induction of immunotolerance in the
      recipient. METHODS: Liver transplantation was performed using male Lewis rats as
      donors and male DA rats as recipients. These rats were randomly allocated into
      the following groups:Control group, Homogeneity Liver Transplantation group, Idio
      immunotolerance group and Acute Rejection group. After transplantation, survival
      time rate of each group were observed. Serum ALT, TB level, Foxp3(+)CD4(+)CD25(+)
      regulatory T cells, expression of GITR on T cell subgroup, histopathology of the
      hepatic graft on day 14, spleen CTL lytic activity on day 14 were measured.
      RESULTS: In the Idio-immunotolerance group, the recipients suffered from
      transient rejection after surgery but acquired immunotolerance and survived long.
      In the Acute Rejection group, the donors were preconditioned with total body
      irradiation before liver transplantation. All recipients died between day 17 to
      21. Serum ALT and TB increased significantly and the ratio of
      Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly compared with
      the Idio-immunotolerance group, the Homogeneity Liver Transplantation group and
      the Control group. The expression of GITR on CD3(+)CD4(+)T cells in the
      peripheral blood decreased, the expression of GITR on CD3(+)CD8(+) T cells and
      CTL lytic activity of the recipients increased by preconditioning of the donors
      with total body irradiation. CONCLUSIONS: Preconditioning of the donors with
      total body irradiation eliminated the passenger lymphocytes of the liver graft,
      decreased the expression of Foxp3(+)CD4(+)CD25(+) regulatory T cells in
      peripheral blood, and increased the expression of GITR on CD3(+)CD8(+) T cells,
      thus affected the course of tolerance and induced acute rejection after liver
      transplantation.

PMID- 20137405
TI  - [Establishment of biological limit value of urinary S-phenylmercapturic acid for
      occupational exposure to benzene].
AB  - OBJECTIVE: To establish the biological exposure limit values of urinary S
      phenylmercapturic acid (SPMA) for assessing occupational exposure to benzene.
      METHODS: Study participants were selected from 55 workers of benzene exposures
      below 32.5 mg/m(3). The concentration of personal exposure to benzene was
      measured by gas chromatography and sampled with personal sampler. The urine
      samples were collected at the end of work shift and individual internal exposure
      level was evaluated by determination of SPMA in urine by HPLC/MS method.
      Comparison of external and internal exposure was assessed by the relative
      internal exposure (RIE) index. RESULTS: The benzene exposure level ranged from
      0.71 to 32.17 mg/m(3) (geometric mean 6.98 mg/m(3), median 7.50 mg/m(3)). The
      urinary SPMA at the end of the work shift were significantly correlated with
      benzene exposure, (microg/g Cr) = -8.625 + 18.367X (mg/m(3)), r = 0.8035, (P <
      0.01). According to the occupational exposure limit for benzene in China and
      calculation of regression equation, the expected value of urinary SPMA was 101.58
      microg/g Cr. Mean level of biotransformation of per mg/m(3) benzene to urinary
      SPMA was 18.23 microg/g Cr and the metabolic efficiencies of benzene
      transformation to urinary SPMA decreased with benzene exposure increased.
      CONCLUSION: Based on abroad documents and data, biological limit value for
      occupational exposure to benzene in China is recommended as follows: 100 microg/g
      Cr (47 micromol/mol Cr) for SPMA in the urine at the end of shift.

PMID- 20137406
TI  - [Effects of carbon disulfide on blood pressure and electrocardiogram for workers
      exposed to levels below the national maximum allowable concentration].
AB  - OBJECTIVE: To study the effects of carbon disulfide exposure within the national
      maximum allowable concentration(MAC) on blood pressure and electrocardiogram, and
      associations with selected factors. METHODS: Workers in a chemical fiber factory
      were divided into two groups based on the type of work: a high exposure group
      (HEG) of 821 individuals and a low exposure group (LEG) of 259. The CS2
      concentration at workplace was controlled under the national MAC. A set of 250
      randomly selected people taking routine physical check-ups in the same period and
      hospital constituted the control group. The systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) were measured on the arm, and the pulse pressure
      (PP) and mean arterial blood pressure (MABP) were calculated based on SBP and
      DBP. The blood pressure data, along with the results of the routine 12-lead
      electrocardiography taken at rest and records on gender, age, years of work, type
      of work, and concentrations of triglycerol, cholesterol, and glucose in blood,
      were compiled for analyses. Risk factors upon CS2 exposure for the increase of
      blood pressure and occurrence of electrocardiogram abnormalities were identified
      and rationalized. RESULTS: Significant difference (P < 0.01) in the average
      values of SBP, DBP, MABP, and the corresponding abnormality incident rates was
      found between HEG and LEG, and between HEG and the control group. For both HEG
      and LEG, the incident rate of DBP abnormality (high DBP) is nearly two times as
      high as that of SBP. Type of work is the largest risk factor in both the high SBP
      and high DBP subgroups, with odds ratios (OR) of 2.086 and 2.331 respectively,
      and high CS2 exposure presents more than double the risk than low exposure. On
      the incident rate of ECG abnormalities, both exposure groups are significantly
      different (P < 0.01) to the control group. High SBP in LEG and high DBP in HEG
      were found to be significant risk factors (OR = 3.531 and 1.638 respectively),
      while blood glucose appears to be a protective factor (OR = 0.747), appealing to
      further investigation. Meanwhile, factors like years of work and cholesterol were
      found to be risk factors in the high SBP subgroup with low exposure, and in the
      high DBP subgroup with high exposure. Within HEG, high DBP is the only blood
      pressure-related risk factor found for the incident of left ventricular high
      voltage (OR = 4.140), as is high SBP for LEG (OR = 4.776). High PP is the only
      risk factor found for repolarization disturbances within LEG (OR = 20.417). While
      blood sugar is a risk factor for origin disturbances, it is a protection factor
      for left ventricular high voltage (OR = 0.633). CONCLUSION: The damage of CS2
      done to the cardiovascular system is a gradual process. Both early and very low
      level exposures are detrimental to the human circulatory system. Below the
      National MAC limit, the toxic effect of CS2 to the cardiovascular system
      increases with time and level of exposure. The effect of CS2 on DBP is more
      significant than on SBP, which indicates that CS2 may affect peripheral resistant
      blood vessels more than the artery. The abnormalities of ECG of workers exposed
      to CS2 are not only the result of high blood pressure on the heart, but also of
      the direct toxicity of CS2 on heart and blood vessels.

PMID- 20137407
TI  - [Effect of neonatal exposure to environmental pollutants on the DNA methylation
      of rat testis].
AB  - OBJECTIVE: To investigate the effects of neonatal exposure of DNA methylation
      inhibitor, Cadmium and PCB153 on DNA methylation, apoptosis and spermatogenesis
      in SD rats. METHODS: Neonatal SD rats were randomly divided into 10 groups and
      received oral administrations of PCB153 (0.025, 0. 250, 2.500 mg/kg), or Cadmium
      (1, 2, 4 mg/kg), or positive control 5-Aza-CdR (0.025, 0.250 mg/kg), or vehicle
      control for five days from PND3. Half of the rats were killed 24 h after the last
      administration. The remains were fed until 12 weeks. Sperm numbers, apoptosis and
      DNA methylation levels in testis were investigated. RESULTS: The daily sperm
      production was significantly decreased in each neonatal exposed group (P < 0.05).
      Neonatal rats exposed to 5-Aza-CdR and Cadmium reduced the global DNA methylation
      level, increased apoptosis, while PCB153 exposure did not significantly change
      DNA methylation and apoptosis. CONCLUSION: Neonatal rats exposed to chemicals
      could reduce spermatogenesis via multiple pathways. Lower DNA methylation and
      increased neonatal apoptosis were suggested as one of the causes.

PMID- 20137408
TI  - [Influence of ethylbenzene on the levels of mandelic acid and phenylglyoxylic
      acid in urine, ultrastructure and the expressions of Mitochondrial apoptotic
      related proteins in the rat nephridial tissues].
AB  - OBJECTIVE: To investigate the influence of ethylbenzene on the levels of mandelic
      acid (MA) and phenylglyoxylic acid (PGA) in urine, the ultrastructure and the
      expressions of mitochondrial apoptotic-related genes in the rat nephridial
      tissues. METHODS: Four groups of 10 males of Sprague-Dawley rats were allocated
      randomly into four groups: control (C) group, low (L) group, moderate (M) group
      and high (H) group, and inhaled daily with different doses of ethylbenzene: 0,
      433.5 mg/m(3), 4335 mg/m(3), and 6500 mg/m(3) 6 h per day, 5 days per week for 13
      weeks. The mandelic acid and phenylglyoxylic acid in the urine was assayed by
      high performance liquid chromatography. The ultrastructure of nephridial tissue
      was observed via electron microscope. The protein expression levels of Bax, Bcl
      2, cytochrome C, Caspase-9 and Caspase-3 in nephridial tissues were measured by
      Western blot, respectively. RESULTS: The levels of MA [(0.303 +/- 0.148) mg/L,
      (0.404 +/- 0.154) mg/L] and PGA [(0.168 +/- 0.104) mg/L, (0.174 +/- 0.092) mg/L]
      in the urine of M and H groups were significantly higher than that in the control
      and L group [(0.084 +/- 0.070) mg/L, (0.041 +/- 0.029) mg/L] (P < 0.05,
      respectively). It has been shown a dose-effect relationship between the contents
      of MA, PGA and MA + PGA and inhaled ethylbenzene, respectively. The mitochondria
      of rat nephridial tissue of H group became a compact and vacuolar structure with
      disorder and loss of cristae. The expression levels of Bax in mitochondria of
      nephridial tissues of M and H groups were significantly lower than that in the
      control group (P < 0.05). Caspase-3 expression level in H group was remarkably
      higher than that in the control group (P < 0.05). Compared with the control
      group, the expression levels of cytochrome C and Caspase-9 were enhanced, while
      the expression levels of Bcl-2 were restrained in all ethylbenzene-treated groups
      (P < 0.05, P < 0.05, respectively). The expression levels of Caspase-3 in M and H
      groups were significantly higher than that in the control group and L group (P <
      0.05). CONCLUSION: Ethylbenzene can induce apoptosis in the cells of nephridial
      tissues. The apoptotic mechanism might be involved with up-regulation of Bax,
      cytochrome C, Caspase-9 and Caspase-3, as well as restraint of Bcl-2. The level
      of MA and PGA in the rat urine could be a parameter of biological dose in vivo
      after ethylbenzene inhalation.

PMID- 20137409
TI  - [Effects of behind legs vibrations on erectile function in male rabbits].
AB  - OBJECTIVE: To study the effects of behind legs vibrations on erectile function in
      male rabbits through the concentration of plasma reproductive hormone and the
      expression of nitric oxide synthase (eNOS), endothelin-1 (ET-1) mRNA in vibrated
      male rabbits. METHODS: 30 male adult rabbits were assigned randomly to A group
      (vibration power: 3.02 m/s(2)), B group (vibration power: 6.13 m/s(2)), C group
      (vibration power: 12.26 m/s(2)) and control group. The concentration of
      expression of eNOS, ET-1 mRNA were measured with RT-PCR after rated for 30 days.
      RESULTS: (1) Compared with 0 days vibration, after exposure to vibration for 10,
      20, 30 days, the A, B, C group concentration of plasma T, LH are much lower (P <
      0.05), the concentration of plasma E2 is much higher. (2) Compared with control
      group after exposed for 30 days, the expression of ET-1 mRNA [B group:(17.39 +/-
      4.59) x 104; C group: (36.21 +/- 13.13) x 104 ] were much higher and expression
      of eNOS mRNA [A group: (19.11 +/- 6.83) x 104; B group: (11.86 +/- 3.15) x 104; C
      group: (4.68 +/- 3.26) x 104] was much lower, there were significant differences
      (P < 0.01). CONCLUSIONS: The vibration of behind legs in rabbits resulted the
      concentration of plasma T, LH are much lower, the concentration of plasma E2 is
      much higher, increased the expression of eNOS mRNA, decreased the expression of
      eNOS mRNA, then vary the erectile function.

PMID- 20137410
TI  - [Problems to be resolved urgently on amblyopia diagnosis and prevention in
      China].
AB  - For many years, the best corrected vision less than 0.9 was an unique amblyopia
      diagnostic criteria in the clinical practices in China. Because of no different
      visual acuity criteria for younger-aged children, the amblyopia prevalence was
      increased. In clinical practice, two phenomenons exist in the amblyopia diagnosis
      and prevention. One is that ignores the risk factors for amblyopia development
      and only considers the factor of visual acuity. The other is that only uses a
      corrected visual acuity of 0.9 as diagnostic criteria and ignores the visual
      development with ages. Therefore, it should be taken the different visual acuity
      criteria for amblyopia diagnosis in younger-aged children. And it should be
      emphasized on the co-existed risk factors in the amblyopia diagnosis.

PMID- 20137411
TI  - [What is the role of MR imaging in the diagnosis of strabismus?].
AB  - The advent of magnetic resonance imaging (MRI) has given us previously
      unavailable opportunities to visualize the functional anatomy of extraocular
      muscles and corresponding ocular motor nerves along the intraorbital and
      intracranial course of living subjects. Ophthalmologists should be aware of these
      new MRI techniques. We believe that MRI will play a more marked role in the
      diagnosis and management of incomitant strabismus.

PMID- 20137412
TI  - [Thickness of the retinal nerve fiber layer in unilateral amblyopic patients with
      high myopia in children].
AB  - OBJECTIVE: To investigate the retina nerve fiber layer (RNFL) thickness in
      unilateral amblyopic patients with high myopia. METHODS: Twenty-three cases (23
      eyes) with unilateral high myopia amblyopia were tested by GD(X) ECC with laser
      polarized light scans in the posterior pole of retina, to measure the relative
      RNFL thickness according to papilla optical as a center, 3.2 mm as the diameter
      of outer ring, 2.4 mm as the diameter of inner ring. The relative RNFL thickness
      of high myopia amblyopia was compared with fellow eyes, normal eyes and high
      myopia respectively and statistics analysis. RESULTS: TSNIT average, superior
      average and inferior average of RNFL in high myopia amblyopia became thinning
      (56.39 +/- 5.69, 68.30 +/- 10.16, 67.34 +/- 5.83), it showed statistically
      differences when compared with fellow eyes (t = 2.090, 2.243, 4.236) and normal
      eyes (t = 3.087, 1.025, 3.481) (P < 0.05). RNFL parameters were no statistically
      significant differences between high myopia amblyopia and simple high myopia (t =
      0.872, 0.297, 0.658; P > 0.05). TSNIT average decreases with axial length in high
      myopia amblyopia and high myopia, there was inverse linear correlation between
      RNFL thickness and axial length (r = -0.462, -0.395; P < 0.05). CONCLUSIONS: The
      RNFL thickness of unilateral high myopia amblyopia of children was thinner than
      normal, but there wasn't obvious compared with simple high myopia. The reasons
      for decreased best corrected vision of unilateral high myopia amblyopia in
      children still need further research.

PMID- 20137413
TI  - [Magnetic resonance imaging features in two Chinese family with congenital
      fibrosis of extraocular muscles].
AB  - OBJECTIVE: The aim of this article was to investigate the structural basis of
      ocular motility and visual abnormalities in humans with congenital fibrosis of
      the extraocular muscles (CFEOM). METHODS: 17 volunteers from 2 CFEOM pedigrees
      Clinical ophthalmic and motility examed and 18 normal control subjects were
      correlated with thin-sectioned magnetic resonance imaging (MRI) across the orbit
      and the brain-stem level. RESULTS: Subjects with CFEOM had severe bilateral
      blepharoptosis, limited supraduction, and variable ophthalmoplegia. In affected
      subjects, MRI demonstrated atrophy of the levator palpebrae superioris, all EOMs,
      and the optic nerves, and small or absent orbital motor nerves. The oculomotor
      nerve was most severely hypoplastic, but the abducens was also affected. Subjects
      with CFEOM exhibited subclinical but highly significant reduction from normal in
      mean optic nerve size (P < 0.05). There are also some difference between the two
      CFEOM pedigrees. CONCLUSIONS: These findings suggest that neuronal disease is
      primary in CFEOM, with myopathy arising secondary to abnormal innervation and the
      oculomotor nucleus and trochlear nucleus of the abnormalities defects.

PMID- 20137414
TI  - [Study of ocular surface electromyography signal analysis].
AB  - OBJECTIVE: Test ocular surface electromyography signal waves and characteristic
      parameters to provide effective data for the diagnosis and treatment of ocular
      myopathy. METHODS: Surface electromyography signals tests were performed in 140
      normal volunteers and 30 patients with ophthalmoplegia. Surface electrodes were
      attached to medial canthi, lateral canthi and the middle of frontal bone. Then
      some alternate flashing red lamps were installed on perimeter to reduce the
      movement of eyeball. The computer hardware, software, and A/D adapter (12 Bit)
      were used. Sampling frequency could be selected within 40 kHz, frequency of
      amplifier was 2 kHz, and input short circuit noise was less than 3 microV.
      RESULTS: For normal volunteers, the ocular surface electromyography signals were
      regular, and the electric waves were similar between different sex groups and age
      groups. While for patients with ophthalmoplegia, the wave amplitude of ocular
      surface electromyography signals were declined or disappeared in the dyskinesia
      direction. The wave amplitude was related with the degree of pathological
      process. The characteristic parameters of patients with ophthalmoplegia were
      higher than normal volunteers. CONCLUSION: The figures of ocular surface
      electromyogram obtained from normal volunteers were obviously different with that
      from patients with ophthalmoplegia. This test can provide reliable quantized data
      for the diagnosis and treatment of ocular myopathy.

PMID- 20137415
TI  - [Long term complications of black diaphragm aniridia intraocular lens implant in
      traumatic aniridia].
AB  - OBJECTIVE: To analyze long-term complications of black diaphragm aniridia
      intraocular lens (IOL) implant in traumatic aniridia and to investigate the
      causes and precautionary measures. METHODS: This is a retrospective consecutive
      case study. Five traumatic aniridia cases undertaken black diaphragm aniridia IOL
      implantation in Shandong Eye Institute and Hospital and developed severe
      complications during long-term follow-up were analyzed, including 4 males and 1
      female, averaged 26.8 years old. The follow-up time varied from 42 months to 108
      months. Two cases had implantation of a secondary black diaphragm IOL after pars
      plana vitrectomy. Two cases had implantation of a black diaphragm IOL together
      with cataract extraction. One case implanted a black diaphragm IOL only. RESULTS:
      All patients felt well within a short period after the surgery, symptoms of glare
      and photophobia were improved. A better visual acuity was obtained in a short
      term period. However, severely secondary glaucoma and bullous keratopathy
      occurred in the long-term follow up. Visual acuity decreased to counting finger
      or hand motion. All cases received penetrating keratoplasty and IOL explantation.
      CONCLUSIONS: Black diaphragm aniridia intraocular lens implantation may induce
      severe long-term complications. The indications should be selected seriously and
      closely follow-up is important.

PMID- 20137416
TI  - [Human aqueous humor levels of levofloxacin 0.5%, gatifloxacin 0.3% and
      levofloxacin 0.3% ophthalmic solution after topical dosing].
AB  - OBJECTIVE: To compare the aqueous humor concentration of levofloxacin 0.5%,
      gatifloxacin 0.3% and levofloxacin 0.3% ophthalmic solution after topical dosing
      in human eyes. METHODS: A randomized, double-blind and parallel study was
      conducted. Senile cataract patients (150 eyes in 150 cases) receiving
      phacoemulsification in eye center affiliated second hospital of Zhejiang
      university were randomized into three groups: levofloxacin 0.5%, 50
      eyes;gatifloxacin 0.3%, 50 eyes and levofloxacin 0.3%, 50 eyes. Each group was
      randomized into five sub-groups, with 10 eyes in each sub-group. Each group
      received either levofloxacin 0.5% or topical gatifloxacin 0.3% or levofloxacin
      0.3% preoperatively. One drop of antibiotic was administered every 15 minutes for
      4 doses. More than 100 microl aqueous samples were obtained from different sub
      groups during surgery, 15.0, 30.0, 60.0, 120.0 and 180.0 min after the last drop,
      respectively. Then 100 microl aqueous samples were put into test tube by sample
      injector accurately. Concentration of the antimicrobial agents was determined by
      the HPLC (high pressure liquid chromatography). Variance analysis was performed
      to detect differences among the antibiotic treatment groups. The differences
      between two groups were assumed by t-test. RESULTS: Humor concentration of
      levofloxacin 0.5% (1.61 +/- 0.48), (2.41 +/- 0.80), (2.93 +/- 0.50), (2.56 +/-
      0.63), (1.87 +/- 0.88) mg/L was significantly higher than that of gatifloxacin
      0.3% (0.70 +/- 0.18), (1.29 +/- 0.54), (1.59 +/- 0.67), (1.41 +/- 0.50), (1.13 +/
      0.28) mg/L and levofloxacin 0.3% (0.55 +/- 0.39), (1.15 +/- 0.42), (1.38 +/-
      0.49), (1.02 +/- 0.33), (0.55 +/- 0.31) mg/L at the same period after the last
      drop (F = 23.64, 12.82, 21.13, 25.00, 12.22;P < 0.05). CONCLUSION: Topically
      applied levofloxacin 0.5% had the higher aqueous humor drug level than
      gatifloxacin 0.3% and levofloxacin 0.3%.

PMID- 20137417
TI  - [Impact of regenerated silk protein membrane on the cytokine expression of
      transfected human corneal epithelium cells].
AB  - OBJECTIVE: The purpose of this research was to study the influence of the
      regenerated silk fibroin film (SF) on cytokines expression of transfected human
      corneal epithelial cells (HCECs) and to investigate the possibility of
      constructing biomaterial complex using SF, modified by transgenic cells. METHODS:
      Empirical study.Ad-VEGF(165) was injected into the limbus of a rabbit's cornea to
      induce cornea neovascularization (CNV). CNV was evaluated by growth areas and
      VEGF characteristic was evaluated by immunohistochemistry. HCECs was cultivated
      on silk protein membrane in the cell cultivation plate. Modality of cells,
      activity of cell proliferation and infection efficiency of Ad-VEGF(165) were
      monitored to evaluate the biocompatibility of silk fibroin. The angiogenesis
      related cytokines in the cell cultivation supernatant was measured using ELISA
      method such as vascular endothelial growth factor (VEGF), angiogenin 1 (Ang1),
      epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) in
      the supernatant (Two-way analysis of variance). RESULTS: (1) The area of corneal
      neovascularization was observed to be (7.60 +/- 1.12) mm(2) at 1 week after Ad
      VEGF(165) was injected and it became (12.28 +/- 2.54) mm(2) another three weeks
      later. Positive expression of VEGF in corneal stromal was observed by
      immunohistochemistry at 3 d, 1 week and 1 month after injection. (2) There was no
      difference noticed in amorphous, growth curve and infection efficiency of Ad
      VEGF(165) between both cells culture conditions of silk protein membrane and
      plate cultivation. (3) After transfection, the concentration of VEGF, Ang1, EGF
      and TGF-beta expressions in the corneal epithelium cell cultivation supernatant
      with silk protein membrane as carriers was (721.67 +/- 66.97) ng/L, (1042.67 +/-
      315.81) ng/L, (2421.00 +/- 0.00) ng/L, and (313.33 +/- 34.06) ng/L respectively;
      and the concentration of each of the aforementioned expression was (721.67 +/-
      66.97) ng/L, (860.33 +/- 315.81) ng/L, (1960.33 +/- 797.90) ng/L, and (278.00 +/-
      53.11) ng/L without using silk protein membrane as carriers. The increase of VEGF
      (F = 168.16, P < 0.0001), EGF (F = 52.76, P < 0.0001), Ang1 (F = 12.47, P =
      0.001), and TGF-beta (F = 0.008, P = 0.932) in the Ad-VEGF(165) group was
      considered statistically significant; however, there was no evident change in the
      concentration of VEGF (F = 0.071, P = 0.793), EGF (F = 0.563, P = 0.465), Ang1 (F
      = 0.14, P = 0.714), and TGF-beta (F = 0.008, P = 0.932)expressions in the corneal
      epithelium cell cultivation supernatant both with or without using silk protein
      membrane as carriers. CONCLUSION: Same as cell HCECs culturing in the cultivation
      plate, through SF application, VEGF(165) destination gene could be high-level
      expressed in the supernatant having which the HCECs is cultured on SF, and in
      addition, the angiogenesis-related cytokines content of Ang1, EGF, and TGF-beta
      autocrine in the HCECS cultivation supernatant could be high-level expressed as
      well.

PMID- 20137418
TI  - [Ocular manifestations of brainstem tumor].
AB  - OBJECTIVE: To investigate the ocular manifestations of brainstem tumors and to
      avoid misdiagnosis and missed diagnosis. METHODS: This is a retrospective case
      series study. The clinical data of 57 brainstem tumor in-patients were collected
      from 1993 to 2007. The clinical manifestations and the results of related
      examinations were analyzed. RESULTS: The present series included 51 cases of
      brainstem germinoma, 4 cases of cavernous hemangioma, 1 case of hemangioblastoma
      and 1 case of metastatic tumor. In 51 cases of brainstem germinoma, there were 37
      males and 14 females. The first attack age varied from 5 to 55 years old and the
      median age was 23 years old. The high incident ages of brainstem germinoma were
      10 - 35 years. Patients were presented with diplopia, ocular motility
      disturbance, nystagmus, anisocoria, and facial palsy. In 57 patients, diplopia
      was the initial symptom in 12.3% (7/57) cases. The incidence of oculomotor nerve
      paralysis was 17.5% (10/57); trochlear paralysis, 1.8% (1/57); trigeminal nerve
      paralysis, 5.3% (3/57); abducens nerve paralysis, 35.1% (20/57); facial palsy,
      14.0% (8/57); optic disc edema, 19.3% (11/57); nystagmus, 21.1% (12/57) and
      anisocoria, 10.5% (6/57). CONCLUSIONS: Ocular manifestations occur frequently in
      brainstem tumor. Nuclear ophthalmoplegia, nystagmus and other neuro-ophthalmic
      signs provide helpful clues for the diagnosis of brainstem tumor.

PMID- 20137419
TI  - [Comparative assessment of individualized multifocal intraocular lens
      implantation].
AB  - OBJECTIVE: To evaluate the visual quality after combined implantation of
      refractive and diffractive multifocal intraocular lens (MIOLs) in both eyes
      (CustomMatch pattern). METHODS: Prospective, nonrandomized study. Zhongshan
      Ophthalmic Center, Sun yat-sen university, P.R. China. Age-related cataract
      patients, selected according to the inclusion criteria and divided into MIOL
      group and monofocal intraocular lens (SIOL) group, received phacoemulsification
      and were implanted with combined a ReZoom NXG1 IOL in the dominant eye and a
      Tecnis ZM900 IOL in the fellow eye or bilateral Sensar AR40e IOLs. Monocular and
      binocular testing one month after surgery included uncorrected and best-spectacle
      corrected visual acuity at far, intermediate and near distances under 100 cd/m(2)
      and 6 cd/m(2), reading visual acuity and reading speed, defocus curve, and
      subjective vision-related quality of life using questionnaire. RESULTS: Under 100
      cd/m(2) and 6 cd/m(2), binocular mean uncorrected visual acuity at 500 cm in MIOL
      group was logMAR 0.013 +/- 0.149 and logMAR 0.163 +/- 0.220 and binocular mean
      best-spectacle corrected visual acuity was logMAR -0.027 +/- 0.092 and logMAR
      0.109 +/- 0.175 respectively. The mean refraction spherical equivalent for best
      distance corrected visual acuity was (-0.18 +/- 0.85) D and (-0.32 +/- 0.90) D
      respectively. Under 100 cd/m(2), better uncorrected visual acuity (decimal 0.63)
      at 40 cm, 63 cm and 100 cm was achieved in MIOL group. Under 6 cd/m(2), the
      uncorrected visual acuities in MIOL group at 40 cm and 63 cm distance were
      significantly higher than those in SIOL group although there were no
      statistically difference at 100 cm. Uncorrected reading visual acuity and reading
      speed in MIOL group were better than those in SIOL group, while the results in
      reading ability were similar when MIOL group without correction compared with
      SIOL group with correction. The depth of focus was 5.5 diopter in MIOL group. No
      patient in both groups wore glasses for distance and 70% patients in MIOL group
      did not need to wear glasses for intermediate and near distances after surgery.
      CONCLUSION: CustomMatch pattern could provide a satisfactory vision at a full
      range of near, intermediate and far distance and improve the life quality to a
      certain extent.

PMID- 20137420
TI  - [Clinical analysis of macular disease involved by Coats disease].
AB  - OBJECTIVE: To study the characteristic and rule of macular disease involved by
      Coats disease and macular changes after photocoagulation. METHODS: A
      retrospective study was performed on patients firstly diagnosis in our hospital
      from October 2004 to June 2007. 25 cases (26 eyes) were included in this study.
      Enrollment criteria: all the cases had examination of regular anterior segment
      and indirect biomicroscopy associated with fluorescein angiography and optical
      coherence tomography. The relationship among macular disease extent, distance
      from macular to peripheral disease, ratio of retinal vessel leakage scale to the
      whole retina, and different age group was analyzed through cumulative odds
      logistic regression with SAS 8.0. RESULTS: The distance between the border of
      macular disease and posterior border of peripheral leakage ranges from 0-9 PD.
      There was negative relationship between macular disease extent and the distance
      from macular to peripheral disease (chi(2) = 7.3212, P = 0.0068). The ratio of
      retinal leakage scale to the whole retina ranges from 1/8 to 1/1. There was
      positive relationship between macular disease extent and ratio of retinal vessel
      leakage scale to the whole retina (chi(2) = 4.8853, P = 0.0271). Macular disease
      extent shows no significant difference between different age group (chi(2) =
      0.1491, P = 0.6994). The follow-up time after photocoagulation range from 1 to 4
      years. 10 cases (11 eyes) of macular edema complicated with hard exudate showed
      apparent decrease in size and extent of macular disease. The best corrected
      visual acuity stay unchanged or get better. CONCLUSIONS: Macular disease involved
      in Coats disease progresses from peripheral fundus to posterior pole, early
      diagnosis and treatment can avoid or reduce the incidence of macular disease. The
      key point of treatment is to photocoagulated the dilated blood vessel.

PMID- 20137421
TI  - [Expression of suppressor of cytokine signaling in peripheral blood monocular
      cells of patients with Vogt-Koyanagi-Harada disease].
AB  - OBJECTIVE: To investigate suppressor of cytokine signaling (SOCS) mRNA and
      protein expression in peripheral blood mononuclear cells (PBMC) of patients with
      Vogt-Koyanagi-Harada (VKH) disease. METHODS: Blood samples were taken from 15 VKH
      patients with active uveitis, 17 quiescent patients and 16 healthy individuals.
      IFN-gamma, IL-12 and IL-4 in the serum were measured by ELISA. PBMC were
      subjected to analysis of SOCS mRNA and protein expression using quantitative RT
      PCR and western blot, respectively. RESULTS: The level of IL-4 in the serum of
      VKH patients and in controls were (28.40 +/- 5.93) ng/L, (34.5 +/- 9.47) ng/L and
      (11.25 +/- 4.43) ng/L, IL-12 were (24.33 +/- 8.55) ng/L, (11.53 +/- 6.11) ng/L
      and (5.19 +/- 2.43) ng/L, IFN-gamma were (18.05 +/- 2.23) ng/L, (15.53 +/- 2.63)
      ng/L and (1.61 +/- 3.47) ng/L, respectively. The level of IFN-gamma, IL-12 and IL
      4 were all significantly higher in the serum of VKH patients than in controls(P <
      0.01). IL-4 in quiescent patients was higher than in active patients (P < 0.01),
      IL-12 and IFN-gamma were lower in quiescent patients was higher than in active
      patients (P < 0.01, P < 0.05). Cytokine inducible SH2 containing protein (CIS)
      mRNA, SOCS1 mRNA, SOCS2 mRNA, SOCS3 mRNA and SOCS5 mRNA levels in PBMC of VKH
      patients with active uveitis are 0.72, 4.92, 1.09, 0.75 and 1.15 folds than that
      in healthy volunteers, respectively. They are 1.15, 2.25, 1.40, 0.69 and 1.16
      folds in static patients, respectively. Marked decreased expression of CIS
      protein is detected in both active and quiescent patients with no significant
      difference between two groups (both P < 0.01). SOCS1 protein is up-regulated
      significantly in active patients compares to in quiescent patients nor in healthy
      volunteers (P < 0.01, P < 0.05). SOCS3 protein is significantly decreased in
      patients than in controls (both P < 0.05). SOCS5 protein is much higher in
      patients than in controls (both P < 0.01), and even higher in quiescent patients
      than in active episode (P < 0.05). CONCLUSIONS: Up regulation of SOCS1 and SOCS5
      expression and down-regulation of SOCS3 and CIS may correlate with the
      development of a Th1 mediated immune response in VKH disease. There is insidious
      inflammation in VKH patients with clinically quiescent uveitis, and this may be
      one of the causes of persistence and recurrences of uveitis.

PMID- 20137422
TI  - [Form deprivation myopia in C57BL/6 mice].
AB  - OBJECTIVE: To investigate the changes of refraction and ocular biometric
      parameters in form deprived myopia, and try to find the effective duration to
      induce significant myopic shift in C57BL/6 mice. METHODS: It was an experimental
      study. Seventy-four C57BL/6 mice, approximately 23 days old, were divided into
      three groups randomly: FD (Form-deprivation), Recovery and Normal control groups.
      FD group was treated with diffuser worn on one eye for 2 weeks (n = 12), 3 weeks
      (n = 20) and 4 weeks (n = 18), respectively. In Recovery group, diffusers were
      removed after 4 weeks form deprivation, and vertical meridian refraction and
      other biometric parameters were performed immediately on 4(th) and 7(th) day. The
      same measurements were performed in the normal control group at the same time
      points. Refraction was measured by photoretinoscopy and corneal radius of
      curvature (CRC) was measured by a modified keratometry. Corneal thickness (CT),
      anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD),
      and axial length (AL) were measured by optical coherence tomography (OCT) with
      focal plane advancement. RESULTS: The FD eyes were approximately -0.85 D more
      myopic compared to the fellow and the normal control eyes after 2 weeks form
      deprivation (P > 0.05). After 3 weeks form deprivation, treated eye had a obvious
      myopic shift (about -4.27 D) compared to fellow eye, with increased vitreous
      chamber depth and axial length, however, there was no statistic difference among
      FD eye, fellow eye and control eye. And after 4 weeks form deprivation, treated
      eyes were induced significant myopic shift (about -5.22 D) compared with the
      fellow eye. The difference in refraction of form-deprived and fellow eyes was
      significantly correlated with the difference in vitreous chamber depth and axial
      length, which indicate that the induced myopia was mainly axial. The relative
      myopia shifted rapidly diminished in 4 days after removing the diffuser, followed
      by a slower recovery. A complete refraction recovery occurred by 7 days after
      removal of the diffuser compared to the fellow and normal control eyes (P >
      0.05). CONCLUSION: Form deprivation myopia can be induced in C57BL/6 mice, but it
      required longer period than other animals; A complete recovery occurred by 7 days
      after removal of the diffuser.Optical Coherence Tomography is a useful instrument
      to measure mouse eye dimension.

PMID- 20137423
TI  - [Experimental research of endostatin microcapsules by periocular injection].
AB  - OBJECTIVE: To detect the release of endostatin in microcapsules of calcium
      alginate gel by emulsification-internal gelatification technology, to observe the
      distribution of Endostatin microcapsules in the eye by periocular injection and
      biocompatibility. METHODS: The calcium alginate gel microcapsules encapsulating
      endostatin were prepared by emulsification-internal gelatification technology,
      the release of endostatin in microcapsules in vitro was examined by uv
      Spectrophotometry. 32 SD mice were divided into randomly four groups: group A,
      periocular injection of endostatin microcapsules 20 microl (2.4 g/L); group B,
      periocular injection of endostatin protein 20 microl (2.5 g/L); group C,
      periocular injection of null-Microcapsules 20 microl; group D, periocular
      injection of saline 20 microl. Western blot, immunohistochemical and enzyme
      linked immunosorbent assay were used. Protein expression and pathology of the
      heart, liver, spleen, lung, kidney and periocular tissue were examined. Daily
      activities and eating condition were observed.t-test was used to analyze the
      data. RESULTS: SDS polyacrylamide gel electrophoresis showed strap of ES protein.
      Concentration of ES protein in superior schedule fluid gradually increased at 3,
      7, 14, 21 days. A group: ES protein expression were observed in inner nuclear
      layer, outer nuclear layer and RPE lamina after periocular injection 7 or 14
      days. B group: ES protein expression were observed in above tissues at 7 days,
      but not at 14 days. C and D group: ES protein expression were not observed in
      above tissues at 7 or 14 days. The results showed that Endostatin microcapsules
      was able to pass through the sclera and spread out in various retinal tissues.
      Concentration of endostatin in the homogenates of eyeball was (63.16 +/- 7.64)
      microg.L(-1).eye(-1) and (33.2 +/- 5.77) microg.L(-1).eye(-1) respectively after
      one and two weeks in A group, but (33.2 +/- 2.89) microg.L(-1).eye(-1) and (15.73
      +/- 2.08) microg.L(-1).eye(-1). The concentration of endostatin was significant
      difference in two group, A group was obviously larger than B group (t = 6.364 and
      4.920, P = 0.003 and 0.008 respectively). Periocular administration. Daily
      activities and eating condition were normal. The abnormality in important organs
      were not detected by pathologic examination. CONCLUSIONS: Endostatin
      microcapsules is able to release persistently, to pass through the sclera and
      spread out in various retinal tissues. There were good biocompatibility and not
      ill effect remarkably.

PMID- 20137424
TI  - [Experimental study of low molecular weight heparin drug delivery system for
      prevention of posterior capsular opacification in rabbit eyes].
AB  - OBJECTIVE: To investigate the safety and efficacy of low-molecular-weight heparin
      drug delivery system (LMWH DDS) for prevention of posterior capsular
      opacification (PCO) in rabbit eyes. METHODS: (1) To prepare the LMWH DDS by
      freeze-drying way with Polylactic-co-glycolic acid (PLGA) as the carrier, and
      evaluate its release properties in vitro. (2) Fifty New Zealand albino rabbits
      (50 eyes) undergoing phacoemulsification were equally divided into five groups:
      receiving normal saline eye drops (group A), 3 different dose (1 mg, 0.5 mg and
      0.25 mg) of LMWH DDS respectively implanted into the posterior chamber (group B,
      C and D), and a carrier DDS implanted into the posterior chamber (group E). All
      the 50 eyes were examined by slit-lamp microscopy. The low-molecular-weight
      heparin levels in aqueous humor were measured, and the wet posterior capsules
      were weighed. RESULTS: The LMWH DDS prepared with a freeze-dried way has high
      encapsulation efficiency, and the equation of 49-day release curve fitting in
      vitro were were similar to zero order. The fibrin exudation in group B, C and D
      were lower than in Group A and E during the first postoperative day. There were
      10, 2, 3, 9 and 10 eyes that developing PCO in the group A, B, C, D and E,
      respectively. The mean wet-weight of the posterior capsule were (114.59 +/-
      14.58) mg, (24.14 +/- 6.08) mg, (39.23 +/- 17.13) mg, (99.35 +/- 29.37) mg,
      (115.29 +/- 19.87) mg respectively in 5 trial groups. There were stable and high
      concentration of low molecular weight heparin in aqueous of group B and C during
      the 4 weeks (> 20 mg/L), while a instable and lower concentrations in group D.
      The result of optical microscopy and electron microscopy examination indicated
      that fibroblast proliferation was quite active in groups A, D and E, but inactive
      in group B and C. Neither infiltration of inflammatory cells at the cornea, iris,
      trabecular meshwork and ciliary body nor retinal degeneration or necrosis was
      found in any group at 12 weeks. There was no intraocular bleeding in all the five
      groups in the following 12 weeks. CONCLUSIONS: The LMWH DDS prepared by freeze
      drying way with PLGA as the carrier has good slow-release and biological
      tolerance. Implantation of LMWH DDS into the posterior chamber of experimental
      animals can significantly reduce postoperative fibrin exudation, and can safe and
      effective prevent the occurrence of PCO, and also there were some dose-effect
      relationship.

PMID- 20137425
TI  - [Empirical study on nano-fluorouracil-coated intraocular lens inhibiting
      posterior capsule opacification].
AB  - OBJECTIVE: To prepare nano-fluorouracil-coated intraocular lens (IOL) and to
      investigate its effect and feasibility of inhibiting posterior capsule
      opacification (PCO) of rabbit. METHODS: Nano-fluorouracil is cross linked with
      IOL with the technology of energy-loaded particle beam. Forty New Zealand white
      rabbits were medially divided into 2 groups named group A and B randomly. All the
      crystalline lens of the left eyes were emulsified and evacuated of by the same
      operator, and then different treatment in different groups. In group A, the
      control group, the Polymethylmethacrylate (PMMA) IOLs were implanted. In group B,
      the nano-fluorouracil-coated IOLs were implanted. Slit-lamp-micrographscopy,
      histopathologyscopy and electron-microscopy were performed when 4 weeks after the
      operations. RESULTS: The incidence rate and severity degree of PCO in control
      group is higher than the other group. The inflammatory reaction of anterior
      segment of the left eyes were remarkably occurred in group A. While almost no
      inflammatory reaction of anterior segment of the left eyes occurred in group B.
      CONCLUSIONS: With implanting nano-fluorouracil-coated IOLs after
      phacoemulsification and evacuation of the crystalline lens can inhibit PCO
      actively and have slight toxic reaction and damage in the eyes.

PMID- 20137426
TI  - [Advanced research in the retinal prosthesis].
AB  - Any disease in visual pathway will affect the visual signal transmission, even
      more seriously, leading to irreversible blindness. The study of retinal
      prostheses is that retinal microelectrodes are implanted into different places of
      retina, and retinal microelectrodes set off electrical signals or deliver
      neurotransmitters, so as to excite and activate retinal neurons. This review
      describes the construction, mechanism, way of implantation, influencing factor,
      advantage and shortcoming, effect of post implantation, biocompatibility of 3
      types of retinal prostheses.

PMID- 20137427
TI  - [Focusing on phacoemulsification with microincision in cataract patients].

PMID- 20137428
TI  - [The challenge and strategy in the surgeries of complex cataract].

PMID- 20137429
TI  - [Screening of cataract surgery in four rural populations aged 50 years old and
      above in western China].
AB  - OBJECTIVE: To estimate the cataract surgical coverage and cataract surgery rate
      and to assess the visual outcome of cataract surgery among individuals aged at or
      over 50 years old in four rural populations from four different areas of western
      China. METHODS: This cross-sectional study, performed during the period 2003 -
      2005, used the method of cluster sampling and recruited 5562 persons aged 50
      years old or above through household census. Standardized ocular examinations
      including visual acuity test, intraocular pressure measurement, slit-lamp and
      fundus examination were performed. The main outcome criteria were cataract
      surgical coverage, cataract surgery rate, complication rate and visual outcome
      after cataract surgery. RESULTS: Of individuals with bilateral presenting visual
      acuity < 6/60 due to age-related cataract, the cataract surgical coverage was 54%
      in Qinghai. It was the highest among these four populations. The highest cataract
      surgery rate (CSR) value was 1551 in Qinghai and the lowest 143 in Guangxi during
      the period of 2000-2002. The overall intraocular lens implantation rate was 51.5%
      in 200 eyes with cataract surgery and 40.5% eyes with post-operative visual
      acuity < 6/60. The overall post-operative complication rate was 28%. CONCLUSION:
      In the beginning of 21st century, the cataract surgical coverage in four rural
      populations aged 50 years old or above in western China was low and similar to
      the situation of the last decade in eastern China. Cataract surgical technique
      and low IOL implantation rate are the main causes for a poor visual outcome. To
      reduce the risks of cataract blindness, the clinicians should substantially
      improve the visual outcome as well as the number of cataract surgery.

PMID- 20137430
TI  - [Study of different methods in reducing conjunctival bacteria before cataract
      surgery].
AB  - OBJECTIVE: To study the conjunctival bacteria flora in eyes of patients
      undergoing cataract surgery and determine the efficacy of reducing conjunctival
      bacteria with different methods. METHODS: A total of 135 eyes of 135 patients
      scheduled to undergo cataract surgery were randomized into 3 groups (45 each).
      They received topical prophylactic treatment with three different kinds of
      antibiotics (0.5% levofloxacin, 0.3% levofloxacin and 0.3% tobramycin). Each
      group was randomized into one-day group and three-day group. All the eyes
      underwent irrigation of fornices with 2.5% povidone-iodine (PVI) before surgery.
      Conjunctival cultures were obtained at various time points. RESULTS: The total
      positive rate of conjunctival cultures was 66.7%. The eliminating rate of
      conjunctival bacteria in one-day groups were 72.7%, 72.7% and 61.1% (P = 0.667)
      while 70.0%, 70.0% and 55.5% in the three-day groups respectively (P = 0.751).
      Immediately after PVI irrigation, the eliminating rate in one-day groups added up
      to 86.4%, 77.3% and 88.9% (P = 0.564) as compared with 90.0%, 80.0% and 66.7% in
      the three-day groups respectively (P = 0.749). And there was no statistically
      significant difference between one-day groups and three-day groups in the
      eliminating rate of conjunctival bacterial after the topical antibiotic
      application. The MIC test revealed that the antibiotic sensitivity of Gram
      positive cocci (G(+)C) to levofloxacin was 94.8% versus 74.1% to tobramycin (P =
      0.000) while the antibiotic sensitivity of Gram-negative bacillus (G(-)B) to
      levofloxacin was 94.4% versus 83.3% to tobramycin (P = 0.289). CONCLUSION: G(+)C
      accounts for the most among the conjunctival bacteria flora in eyes of patients
      undergoing cataract surgery and there is no statistically significant difference
      in the efficacy of reducing conjunctival bacteria between the application of
      topical antibiotic for one day and for three days. Both G(+)C and G(-)B retain a
      high sensitivity to levofloxacin. Topical antibiotic in combination with 2.5% PVI
      irrigation further reduces conjunctival bacteria.

PMID- 20137431
TI  - [Relative factors of retinal detachment after phacoemulsification cataract
      extraction and intraocular lens implantation].
AB  - OBJECTIVE: To investigate the incidence and related factors of retinal detachment
      (RD) after phacoemulsification cataract extraction and intraocular lens (IOL)
      implantation in an unselected patient group. METHODS: This retrospective review
      was comprised of 10 076 cataract patients (13 625 eyes) who had
      phacoemulsification cataract extraction and IOL implantation from December 1,
      1998 to September 30, 2008. The patients were of different ages, gender, left or
      right eye and different type of cataracts. The incidence of postoperative RD was
      assessed and the relative risk factors were estimated using the Kaplan-Meier
      method. RESULTS: The average age was 67.22 +/- 15.10 years old with 4439 males
      and 5637 females. The difference between the numbers of men and women was
      statistically significant (chi(2) = 142.44, P < 0.01). A total of 6701 left eyes
      and 6924 right eyes showed no significant difference (chi(2) = 3.65, P = 0.056).
      And 65.91% of these eyes were age-related cataract. During the post-operation
      observation period, 32 eyes of RD in 32 patients were observed from 10 days to 74
      months post-operation. The ratio was 0.32% with an estimated risk (Kaplan-Meier)
      of 0.47% at 74 months. These results confirmed that myopia and increased axial
      length were significantly associated with RD (chi(2) = 14.55, P < 0.001) and
      recognized risk factors for RD such as high myopia, posterior capsular bag
      rupture and Nd: YAG capsulotomy. Among these 32 eyes, 31 eyes had one successful
      retina re-attaching operation (90.32%) and two eyes were given up because of post
      operative relapse. CONCLUSION: The incidence of RD increases after
      phacoemulsification cataract extraction and IOL implantation in an unselected
      patient group. Hypermyopia, posterior capsular bag rupture and Nd: YAG
      capsulotomy are possible risk factors of the RD.

PMID- 20137432
TI  - [A multi-center randomized controlled trial of social skills training among
      children with behavior problems].
AB  - OBJECTIVE: To investigate the feasibility and effectiveness of a social skills
      training program in children with child behavior disorders. METHODS: A total of
      441 children, aged 7-13 years old, from 6 centers were randomized into
      intervention (n = 216) and waitlist group (n = 225). The social skills training
      program was offered to the intervention group 1 hour weekly for totally 12 weeks.
      The Rutter Parent & Teacher Scale and Achenbach Child Behavior Checklist (CBCL)
      were used at baseline and completion of intervention. RESULTS: Change of total
      score, neurotic factor score and antisocial factor score of Rutter Parent Scale
      in the intervention group was significantly larger than that in the waitlist
      group (P = 0.000, P = 0.000, P = 0.000). The clinical cure rate of the
      intervention group (47.69%) was significantly higher than that of the waitlist
      group (24.89%) after intervention (chi(2) = 24.84, P = 0.000). Change of total
      score, neurotic factor score and antisocial factor score of Rutter Teacher Scale
      in the intervention group was significantly larger than that in the waitlist
      group (P = 0.000, P = 0.003, P = 0.002). The clinical cure rate of the
      intervention group (56.02%) was significantly higher than that of the waitlist
      group (38.22%) after intervention (chi(2) = 14.01, P = 0.000). The total score,
      somatic complaint score and delinquent score of Achenbach Child Behavior
      Checklist (CBCL) of the intervention group decreased significantly than that of
      the waitlist group after intervention (P = 0.000, P = 0.000, P = 0.002) with the
      exception of aggressive behavior score (P = 0.078). The difference and decrease
      rate of total score, somatic complaint score, delinquent score and aggressive
      behavior score of intervention group were significantly higher than that of the
      waitlist group after intervention (P = 0.000, P = 0.000, P = 0.006, P = 0.015, P
      = 0.000, P = 0.000, P = 0.000, P = 0.012). CONCLUSION: This study provides
      supports for the use of social skills training program to improve children's
      behavior problems in both family and school settings.

PMID- 20137433
TI  - [Revised amyotrophic lateral sclerosis functional rating scale at time of
      diagnosis predicts survival time in amyotrophic lateral sclerosis].
AB  - OBJECTIVE: To identify the correlation between the revised amyotrophic lateral
      sclerosis (ALS) functional rating scale (ALSFRS-R) and the progression rate of
      ALSFRS-R (DeltaFS) at time of diagnosis and survival time in a prospective
      survey. METHODS: A total of 129 consecutive patents with definite or probable ALS
      were enrolled at our hospital from January 2002 to December 2005. The patients
      were monitored with a standard evaluation form recording clinical features,
      ALSFRS-R and forced vital capacity (FVC) every 3 months from visit to death or
      tracheostomy. RESULTS: The mean age at onset was (52 +/- 11) years old. The
      median survival time from symptom onset was 45.71 months (95% CI = 35 to 51). In
      univariate analysis of Kaplan-Meier method, the outcome was significantly related
      to total ALSFRS-R and DeltaFS (P < 0.05). In Cox multivariate model, DeltaFS and
      FVC% were both statistically significant predictors of survival after adjusting
      for age and onset site (P < 0.05). Al-unit decrease in DeltaFS was associated
      with a 73.3% decreased risk of death. CONCLUSION: ALSFRS-R is sensitive to the
      change over time and can predict survival at diagnosis. It can be used as a
      primary outcome measure in ALS clinical trial. DeltaFS at diagnosis can provide
      us the information of disease progression at one particular point. It is a more
      significant predictor of survival in patients with ALS as compared to total
      ALSFRS-R and time from onset to diagnosis.

PMID- 20137434
TI  - [Study on expressions of CD25 and CD127 in CD4+ peripheral T lymphocytes of
      patients with rheumatoid arthritis].
AB  - OBJECTIVE: To study the proportion of regulatory T cells (Tregs) in peripheral
      blood of patients with rheumatoid arthritis (RA) and investigate the significance
      of Tregs change in the incidence and inflammatory activity of RA. METHODS: Three
      color fluorescence flow cytometry was used to detect the CD4, CD25 and CD127
      markers in the peripheral blood lymphocytes of 25 RA patients and 31 healthy
      volunteers (HVs). The proportions of CD4(+)CD25(+), CD4(+)CD25(high),
      CD4(+)CD25(+)CD127(-) and CD4(+)CD25(high)CD127(-) cells were compared between
      the two groups and correlation analysis was conducted between Tregs and disease
      activity indices which including disease activity score (DAS28-4), tender joint
      count (TJC), swollen joint count (SJC), time of morning stiffness, patient's
      global assessment of disease activity on a 100 mm VAS by doctor and patients,
      erythrocyte sedimentation rate and C-reactive protein. RESULTS: The proportions
      of CD4(+)CD25(+)CD127(-) and CD4(+)CD25(high)CD127(-) cells in CD4(+) peripheral
      T lymphocytes were (2.53 +/- 0.85)% and (0.91 +/- 0.32)% respectively in RA
      group, while they were (3.22 +/- 0.97)% and (1.25 +/- 0.41)% in HV group. Both of
      the proportions of CD4(+)CD25(+)CD127(-) and CD4(+)CD25(high)CD127(-) cells were
      lower in RA group comparing with HV group, and both were significantly different
      between the two groups (P < 0.05). Correlation analysis indicated significant
      negative correlations of the proportions of CD4(+)CD25(+)CD127(-) and
      CD4(+)CD25(high)CD127(-) cells with DAS28-4 and TJC (P < 0.05), furthermore,
      CD4(+)CD25(high)CD127(-) T cells still showed significant negative correlation
      with the SJC and patient's global assessment of disease activity on a 100 mm VAS
      by patients (P < 0.05). CONCLUSION: The proportion of Tregs decreased in
      peripheral blood lymphocytes of patients with RA and the abnormality of Tregs may
      play an important role in the incidence and inflammatory activity of RA.

PMID- 20137435
TI  - [Analysis of serum protein fingerprints on non-small cell lung cancer lymphatic
      metastasis].
AB  - OBJECTIVE: To establish a classification model and serum proteomic patterns in
      non-small cell lung cancer (NSCLC) patients with lymph node metastasis by surface
      enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF
      MS). METHODS: The relative contents of serum proteins of 84 NSCLC patients with
      different N stages (35 N0 cases, 19 N1 and 30 N2 respectively) were detected by
      CM10 chip and SELDI-TOF-MS; two decision trees were generated to distinguish
      lymph nodes metastasis (N0 versus N1 + N2) and mediastinal lymph nodes metastasis
      (N0 + N1 versus N2) respectively. RESULTS: The model in which 50 patients were
      randomly chosen differentiated patients with lymph nodes metastasis from N0
      patients with a sensitivity of 96.3%(26/27) and a specificity of 95.7%(22/23) in
      the training set, a following blind test was taken. Subsequently, compared with
      49 patients with lymph node metastasis (N1 + N2), 15 patients with total negative
      lymph nodes (including lobar, segmental and subsegmental nodes necessarily) were
      defined as "true" N0 and were chosen to form a better predictive model with a
      77.6% (38/49) sensitivity and a 93.3% (14/15) specificity respectively. And
      6682.0Da, together with other five proteins, had significant difference between
      two groups; the result of this model for distinguishing the mediastinal lymph
      nodes metastasis is more accurate than thoracic CT analyses by Alongi F and many
      other clinical centers. It had a sensitivity of 80.0% (24/30) and a specificity
      of 77.8% (42/54) respectively. CONCLUSION: SELDI-TOF-MS showed a potential value
      for predicting lymph nodes metastasis in NSCLC patients. And further studies are
      required to confirm the models and identify the related proteins.

PMID- 20137436
TI  - [A prognostic analysis of N0-1M0 intralobar metastatic non-small cell lung
      cancer].
AB  - OBJECTIVE: To assess whether it is reasonable to downgrade intralobar metastatic
      non-small cell lung cancer from T4 disease through a prognostic analysis of N0
      1M0 disease. METHODS: A retrospective analysis was conducted to assess the
      survival of patients with intralobar metastatic non-small cell lung cancer with
      pathological N0-1M0 disease. The Kaplan-Meier method was used to calculate the
      patient survival. RESULTS: Forty-six patients were included. The overall 5-year
      survival rate was 29.2% with a median survival of 53.0 months. The median
      survival was 24.0 months for patients with adenosquamous carcinoma; while for
      patients with other pathologic types, the median survival was 48 months.
      Adenosquamous carcinoma had a shorter survival time than other pathologic types
      (P = 0.003). The median survival time was 60.0 months for patients undergoing non
      pneumonectomy resection and 24 months for patients undergoing pneumonectomy (P =
      0.023). CONCLUSION: It is reasonable to downgrade the T4 classification of non
      small cell lung cancer with intralobar metastasis. However, pneumonectomy should
      be carried out with cautions. Adenosquamous carcinoma has a poor prognosis.
      Further study of a larger sample size is warranted.

PMID- 20137437
TI  - [Intradiscal interventional therapy for degenerative chronic discogenic low back
      pain with end-plate Modic changes].
AB  - OBJECTIVE: To observe the different efficacies of intradiscal interventional
      therapy for patients with degenerative chronic discogenic low back pain and end
      plate Modic changes through different types of injection and to evaluate the
      potential therapeutic value of intradiscal injection treatment for degenerative
      chronic discogenic low back pain with different types of end-plate Modic changes
      by using appropriate injection. METHODS: Patients with single segmental
      degenerative chronic discogenic low back pain proved by discography were
      classified as Modic type I predominant change (including Modic Type I & Modic
      type I predominant mixed Type I/II) and Modic type II predominant change
      (including Modic Type II & Modic Type II predominant mixed Type II/I) according
      to the end-plate Modic changes on MRI. All received the intradiscal injection
      treatment. Patients were divided into three groups: (1) A group (control group):
      intradiscal injection of normal saline 3 ml; (2) B group (treatment group):
      intradiscal injection of diprospan (compound betamethasone) 3 ml; (3) C group
      (treatment group): interventional injection of diprospan (compound betamethasone)
      1 ml + songmeile (cervus & cucumis polypeptide injection) 2 ml. Pain and function
      were evaluated by pain visual analogue scale (VAS) and Oswestry disability index
      (ODI). T-test was applied for efficacy comparison in each group at pre-operation,
      3 months and 6 months post-operation. RESULTS: Sixty patients were included.
      There were 39 males and 21 females with a mean age of 41.6 years old (26 - 58).
      There were 10 patients in each group: A-Modic I, A-Modic II; B-Modic I, B-Modic
      II; C-Modic I, C-Modic II. There was no significant statistical difference in
      preoperative VAS and Oswestry scores among groups; VAS and Oswestry scores of B
      group and C group at 3 months and 6 months post-operation were significantly
      better than those pre-operative scores, and also better than that of control
      group (A group) at the same time. But there was no significant difference in
      scores between 3 months and 6 months in ether B group or C group, and there was
      also no significant difference in VAS and Oswestry scores between B group and C
      group at various time points. Various Modic types had no correlation with either
      VAS score or Oswestry score in each group at various time points. CONCLUSION:
      Intradiscal interventional therapy can relieve discogenic low back pain and
      improve Oswestry disability index score of function between 3 and 6 months post
      operation. There is no significant difference in post-operative efficacy between
      Modic Type I and Modic Type II. Steroids are the major analgesic factor of
      intradiscal injection. But the synergistic application of songmeile (cervus &
      cucumis polypeptide injection) can maintain the analgesic effect and duration
      with a decreased dose of steroids.

PMID- 20137438
TI  - [Apical pedicle subtraction osteotomy in the treatment of severe rigid
      kyphoscoliosis:a preliminary report].
AB  - OBJECTIVE: To evaluate the safety and efficacy of apical pedicle subtraction
      osteotomy (PSO) in the treatment of severe kyphoscoliosis. METHODS: The
      radiographic films of the 12 severe kyphoscoliosis patients treated with apical
      pedicle subtraction osteotomy were retrospectively reviewed, and the Cobb angles
      of the scoliosis and kyphosis and coronal trunk balance were measured and
      analyzed. Medical records and operation charts were reviewed to record any peri
      operative complications. RESULTS: Twelve patients were included in this study, 4
      males and 8 females, with an average age of 20.1 years old. Of the 12 patients, 2
      were adult kyphoscoliosis and 10 were congenital kyphoscoliosis. The mean follow
      up time was 9.2 months. The mean fusion levels were 12 segments and the mean
      operation time was 5.0 hours. The mean estimated blood loss during operation was
      1517 ml and the mean autotransfusion and allotransfusion were 780 ml and 1109 ml,
      respectively. The mean preoperative and postoperative coronal Cobb angle of the
      main curve was 100.9 degrees and 48.8 degrees , with an average correction rate
      of 51.8% (P = 0.000). The mean preoperative and postoperative sagittal Cobb angle
      of the kyphosis was 81.7 degrees and 42.2 degrees , with an average correction
      rate of 49.8% (P = 0.000). At final follow-up, the mean Cobb angles of the
      scoliosis and kyphosis were 50.7 degrees and 46.0 degrees , respectively, and no
      obvious correction loss was found (P = 0.763, P = 0.698). The mean coronal trunk
      balance before, after surgery and at final follow-up was 16.3 mm, 14.7 mm, and
      12.0 mm, respectively. Only 1 patient had trunk shift greater than 20 mm at final
      follow-up. After operation, two patients suffered from transient numbness and
      weakness of the unilateral lower extremity with complete recovery in one week. No
      spinal cord injury occurred. CONCLUSIONS: Apical pedicle subtraction osteotomy
      can be easily performed in the treatment of severe rigid kyphoscoliosis with
      satisfactory correction results and few neurologic complications.

PMID- 20137439
TI  - [Role of testosterone in tumor necrosis factor-alpha and monocyte chemotactic
      protein-1 expression in mouse macrophage RAW264.7 and its molecular mechanism].
AB  - OBJECTIVE: To investigate the role of androgen in TNF-alpha and MCP-1 expression
      in RAW264.7 macrophage and its molecular mechanism. METHODS: (1) RAW264.7
      macrophage was treated with 10(-9) mol/L or 10(-7) mol/L testosterone (T) and
      then subjected to the measurement of: 1) the cellular expression of TNF-alpha and
      MCP-1 mRNA by RT-PCR; 2) the expression of TNF-alpha and MCP-1 in cell culture
      supernatant by ELISA; (2) The expression of phospho-NF-kappaB after treatment
      with T was measured by Western blot. (3) Cells were pre-incubated with 10(-4)
      mol/L PDTC (an inhibitor of NF-kappaB) for 1 hour, followed by T treatment.
      Expression of mRNA and supernatant levels of TNF-alpha and MCP-1 were measured by
      RT-PCR and ELISA. RESULTS: (1) 1) After a 6 h treatment with 10(-9) mol/L or 10(
      7) mol/L T, the expression of TNF-alpha mRNA increased by 1.78 and 1.87 folds,
      MCP-1 by 1.58 and 1.66 folds respectively (all P < 0.05). 2) Incubated with both
      concentration of T for 6 h showed no significant changes of supernatant levels of
      TNF-alpha and MCP-1. After a 24 h treatment, the levels of TNF-alpha and MCP-1
      increased significantly (all P < 0.05) while more significant increase was found
      in 10(-7) mol/L T group (P < 0.05). (2) The expression of phospho-NF-kappaB
      (ser276) increased significantly after cells were treated with 10(-7) mol/L T for
      30 min (P < 0.05) and peaked at 60 min. (3) With 1 h PDTC pre-incubation, T (10(
      9) mol/L or 10(-7) mol/L) treatment for 6 h led to a lower mRNA expression and 24
      h led to lower supernatant levels of TNF-alpha and MCP-1 than those without (P <
      0.05). However, both cellular and supernatant expression of TNF-alpha and MCP-1
      with PDTC pre-incubation were still higher than those of blank controls (all P <
      0.05, except for TNF-alpha in 10(-9) mol/L T treatment). CONCLUSION: Testosterone
      can increase TNF-alpha and MCP-1 expression in RAW264.7 macrophage in vitro.
      Activation of cellular NF-kappaB by testosterone may be one of underlying
      molecular mechanisms.

PMID- 20137440
TI  - [Study of adventitial inflammation and inflammatory factors in pathogenesis of
      allograft arteriosclerosis in rats].
AB  - OBJECTIVE: To study the roles of serum inflammatory factors IL-6 and TNF-alpha
      and allograft adventitial inflammation in the pathogenesis of allograft
      arteriosclerosis in rats. METHODS: Thirty-six allogeneic allograft rats and 16
      syngeneic allograft rats were randomly divided into 4 groups (9 rats in each
      experimental group and 4 in each control group): A, harvested at Week 1 post
      operation; B, harvested at Week 2 post-operation; C, harvested at Week 3 post
      operation; D, harvested at Week 4 post-operation. Blood samples were collected
      before transplantation and after harvest. The method of ELISA was used for
      testing serum inflammatory factors including interleukin-6 (IL-6), tumor necrosis
      factor-alpha(TNF-alpha), HE staining for pathologic changes of aortic allograft
      and immunohistochemical method for expression of alpha-actin, cyclin dependent
      kinase-1 (CDK(1)) and proliferating cell nuclear antigen (PCNA). Compare the
      inflammatory factors and other observations between groups and preoperative.
      RESULTS: At Week 1 post-operation, a large amount of inflammatory cell
      infiltration in adventitia was observed; at Week 2 post-operation, slight
      collagen fibers hyperplasia with inflammatory infiltration; at Week 4 post
      operation, obvious adventitia thickening with a large number of smooth muscle
      cells, collagen fibers and inflammatory cells, smooth muscle cells migration from
      adventitia to intima. Expressions of alpha-actin, CDK(1) and PCNA kept increasing
      with time in adventitia (P < 0.05). There was a significant increase in serum TNF
      alpha level in Groups A, B, C and D, as compared with pre-operative basal level
      (P < 0.01). There was no difference between controls and pre-operative basal
      level. IL-6 level slightly declined in the middle stage, but finally increased in
      experimental group B (P < 0.05) while it significantly increased in Groups A, C,
      D (P < 0.01). In the control groups A, B, C, it was higher than pre-operative
      level (P < 0.05). In experimental groups A, C, D, it had a significant increase
      as compared with controls (P < 0.01). CONCLUSIONS: In abdominal aortic allograft
      models, obvious angiosclerosis was found in adventitia and intima in accordance
      with the severity of adventitial inflammation. Thus the inflammatory factors and
      inflammatory cell infiltration in adventitia are both involved in the
      pathogenesis of early allograft arteriosclerosis.

PMID- 20137441
TI  - [Impact of artificial esophagus slipped time upon the function formation of
      neoesophageal channel].
AB  - OBJECTIVE: To observe the impact of artificial esophagus slipped time upon the
      function formation of neoesophageal channel, explore the scope of secure control
      time and assess the treatment methods of neoesophageal stenosis. METHODS: A total
      of 18 pigs in which artificial esophagus slipping at Month 1, 2, 3, 6 post
      operation were observed with regards to complications, neoesophageal structures
      and functions and survival status of experimental animals. RESULTS: Three pigs
      had a slip of artificial esophagus within a month post-operation and severe
      eating difficulties (Bown's Grade IV) because the neoesophagus had a severe
      narrowing (< 0.5 cm). All were dead shortly resulting from a failed treatment of
      esophageal dilation. Four pigs had a slip of artificial esophagus within 2 months
      post-operation. They all had dysphagia (Grade III-IV) as a result of moderate or
      severe neoesophageal stenosis (0.5 - 0.9 cm). Dysphagia was progressive. Repeated
      esophageal dilation was in vain. Three pigs were dead shortly and 1 pig achieved
      a long-term survival through a bare stent replacement therapy. Four pigs had a
      slip of artificial esophagus within 3 months post-operation. Dysphagia (Grade I
      II) occurred as a result of mild or moderate neoesophageal stenosis (0.9 - 1.5
      cm). Two pigs with moderate dysphagia achieved a long-term survival through a
      bare stent replacement therapy while another two were sacrificed. Seven had a
      slip of artificial esophagus at 3 months post-operation. The neoesophagus showed
      expansion and a relative narrowing (> 1.9 cm). Experimental animals had a mild
      difficulty in eating (Grade I), but it had an automatic relief. Experimental
      animals achieved a long-term survival and did not advance further. CONCLUSION:
      Artificial esophagus (implant) stays in place for 2 - 3 months to form a
      functional esophageal channel. The longer an artificial esophagus is in place, a
      better channel of neoesophagus will form. Resetting a bare stent treatment of
      serious neoesophageal stenosis has significant therapeutic effects during this
      period. At 3 months post-operation, the slipping of artificial esophagus has
      little effects upon eating so that experimental animals may achieve a long-term
      survival.

PMID- 20137442
TI  - [Reducing blindness and visual impairment from glaucoma is an important component
      in the prevention of blindness].
AB  - International ophthalmological societies and World Health Organization (WHO) have
      recognized the severity of glaucoma problem and the importance for promoting the
      glaucoma control worldwide. WHO has taken some measures to reinforce the global
      prevention of blindness from primary glaucomas. The rationale to deal with the
      glaucoma problem is that glaucomas produce a significant global public health
      burden at present, and glaucoma can be effectively treated once detected
      according the evidenced-based practice protocols for glaucoma management. Taking
      the glaucoma control as the priority for prevention of blindness means not only
      apply the clinical path, but also apply public health path and integrate various
      levels of ophthalmic manpower to deal with glaucoma problem. That is a great
      change in the prevention and management of glaucomas. Screening and early
      detection of glaucoma cases is very important in glaucoma control. At present,
      enhancing opportunistic case detection has been used to find more undiagnosed and
      untreated glaucoma cases, since evidence regarding the benefits of population
      based screening is currently lacking. The scope of intervention strategies for
      glaucoma control should be matched with the local socio-economic status, thus the
      initiative for glaucoma control can be smoothly developed and progressed.

PMID- 20137443
TI  - [New technologies for glaucoma diagnosis require evaluation of their clinical
      application].
AB  - Optical coherence tomography (OCT), Heidelberg Retinal Tomography (HRT-II) and
      GDx have been used widely in glaucoma diagnosis for many years, but it is still
      uncertain in their practical value and clinical significance. Therefore, it
      requires an evaluation for the usefulness of each instrument in the diagnosis of
      glaucoma. The evaluation must be correct, standardized and strict in methodology,
      with emphasis on the early diagnosis and the concrete analysis of each parameter
      given by the different imaging instruments. Only if clinical application of these
      devices is combined with the practical evaluation, can these techniques make real
      progression and solve the clinical problems in the early diagnosis of primary
      open angle glaucoma.

PMID- 20137444
TI  - [Effect of fundus image devices for early diagnosis of primary open angle
      glaucoma].
AB  - Evaluation of the optic disc and retinal nerve fiber layer measurements (RNFL)
      with stereophotography is the current "gold standard" for the diagnosis of early
      primary open angle glaucoma (POAG), but it is still subjective and is dependent
      too much upon an experienced observer. Substantial variability exists in the
      interpretation of optic disc change over time. There are consistent evidences
      that image analysis devices such as optical coherence tomography (OCT) and
      Heidelberg retina tomograph (HRT-II) can detect early to moderate glaucoma as
      well as expert assessment of stereoscopic optic disc and RNFL photographs. Optic
      disc and RNFL defect can be quantitatively measured by these devices. But the
      sensitivity and specificity of the measurements obtained with these devices are
      not good enough for the early diagnosis of POAG at this time due to several
      reasons, such as individual variety of the structure parameters in normal
      subjects, lack of powerful normative database, lack of diagnostic parameters
      which are good enough both in sensitivity and specificity for detecting early
      glaucoma damage. However, information obtained from these image analysis devices
      might be helpful in early POAG diagnosis if clinicians can understand the
      advantages and limitations of these instruments.

PMID- 20137445
TI  - [A novel mutation of CYP1B1 gene in primary congenital glaucoma].
AB  - OBJECTIVE: To investigate the distribution of the CYP1B1 (Cytochrome P450, family
      1, subfamily B, polypeptide 1) gene mutations in primary congenital glaucoma
      (PCG) in Hunan Province. METHODS: Case-control study. Thirteen cases of PCG from
      different districts of Hunan province were collected in this study. Direct
      sequencing was used to evaluate the coding and the promoter regions of the CYP1B1
      gene in PCG patients. RESULTS: A novel pathogenic mutation (c.C319G, L107V) was
      identified in a PCG patient in our study and it was a missense mutation in exon
      2. Additionally, four single nucleotide polymorphisms(SNPs) were found in PCG
      patients, including R48G, A119S, V432L and D449D. CONCLUSION: A novel CYP1B1 gene
      mutation (L107V) may be the cause for primary congenital glaucoma in Hunan
      Province.

PMID- 20137446
TI  - [The efficacy of surgical treatment for encapsulated cystic blebs around the
      plate after Ahmed glaucoma valve implantation].
AB  - OBJECTIVE: To evaluate the efficacy of surgical treatment for encapsulated cystic
      blebs around the plate after Ahmed glaucoma valve implantation. METHODS: This was
      a retrospective observational case series. Thirteen cases with elevated
      intraocular pressure (IOP) induced by fibrous proliferation around Ahmed valve
      were retrospectively studied. The intraocular pressure increased at 3 weeks to 5
      months post-operation (2 months in average). The plates and tubes of Ahmed valve
      were in good position. No obstruction was seen in the tubes. Localized,
      encapsulated, cystic blebs were found in the equator of eyeball in which the
      plates were located. All cases underwent encapsulated cysts resection combined
      with mitomycin-C usage under conjunctival flaps. The excised tissues were sent
      for pathological examination. The changes of IOP and the outcome of the diseases
      were observed. RESULTS: IOP was normal one month after surgery in all cases. The
      success rate was 100%. In the 3 - 20 months follow-up period, the IOP level kept
      normal in 3 cases without any anti-glaucoma medications. The IOP level was in
      normal range in 6 cases using two or three different kinds of anti-glaucoma
      medications. Three cases needed further surgical treatment because of
      uncontrolled IOP even with anti-glaucoma medications. Among them, the complete
      success rate was 75% (3/4) in patients more than 57 years old, while the complete
      success rate was 0 (0/8) in patients less than 37 years old. CONCLUSIONS: It was
      considered an effective method of surgical treatment for encapsulated blebs
      around Ahmed glaucoma valve. The result was better in elderly patients than in
      younger patients relatively.

PMID- 20137447
TI  - [Clinical analysis on sixteen cases of Sturge-Weber syndrome-associated
      glaucoma].
AB  - OBJECTIVE: To investigate the clinical features of Sturge-Weber syndrome
      associated glaucoma and its surgical treatment. METHODS: A retrospective case
      series study. The general clinical data and related ocular manifestations in 16
      patients (21 eyes) with Sturge-Weber syndrome-associated glaucoma in our hospital
      from January 2003 to December 2007 were analyzed retrospectively. RESULTS: Age of
      the patients ranged between 1 month to 31 years old, and the median age was 11
      years. Bilateral facial angiomas were present in 8 patients, and two of them had
      extensive hemangioma. Eleven cases had unilateral glaucoma and 3 of them had
      bilateral facial angiomas. Five patients had bilateral glaucoma and all of them
      had bilateral facial angiomas. Open anterior chamber angle was found in all
      affected eyes by gonioscopy. B-scan ultrasonography was performed in 21 eyes and
      diffused occupying lesions in the choroid were found in 8 eyes (38.1%). Posterior
      bowing of the iris, low echo in ciliary body and shallow ciliary body detachment
      were found by ultrasound biomicroscopy. Anti-glaucoma surgeries including
      trabeculotomy, trabeculectomy, non-penetrating deep sclerectomy, valve
      implantation and cyclocryotherapy were performed in 18 eyes. Eighty percent of
      the eyes which underwent trabeculectomy developed choroidal detachment after
      operation. Ten patients (11 eyes) were followed-up for 22 months on average.
      Intraocular pressure was significantly lower than that before the operation (t =
      5.3956, P < 0.01). Intraocular pressure in all followed-up eyes was controlled at
      < or = 21 mm Hg (1 mm Hg = 0.133 kPa). CONCLUSIONS: The clinical features of
      Sturge-Weber syndrome-associated glaucoma include facial angiomas, open anterior
      chamber angle and choroidal hemangioma. Anti-glaucoma surgery can reduce the
      intraocular pressure effectively.

PMID- 20137448
TI  - [Congenital ectropion uvea and secondary glaucoma].
AB  - OBJECTIVE: To investigate the clinical features of congenital ectropion uvea
      (CEU) and the relationship between CEU and secondary glaucoma. METHODS: This is a
      retrospective case series. Clinical features and treatments of 11 patients with
      CEU were summarized. Combined with the literatures review of CEU, the
      pathogenesis and therapeutic results of secondary glaucoma were analyzed.
      RESULTS: Among these 11 patients, there were 10 patients with secondary glaucoma
      and one patient with ocular hypertension. There were 4 patients complicated with
      congenital ptosis, 2 patients with ocular proptosis, 1 patient with congenital
      cataract, 1 patient with lens subluxation, 3 patients with ankylodactylia and 1
      patient with Rieger's syndrome. The intraocular pressure of 9 patients was
      controlled after the trabeculectomy. CONCLUSIONS: CEU is a rare, nonprogressive
      anomaly accompanied other ocular abnormalities and various systemic disorders.
      The pathogenesis of secondary glaucoma is related to iridotrabecular dysgenesis.
      It is essential to detect and to treat the secondary glaucoma as early as
      possible.

PMID- 20137449
TI  - [Changes of structures of anterior chamber angle in rabbit chronic high
      intraocular pressure model].
AB  - OBJECTIVE: To observe the anterior chamber angle changes occurred in compound
      Carbomer-induced chronic high intraocular pressure (IOP) model in rabbit eyes.
      METHODS: It was an experimental study. Thirty two rabbits were randomly divided
      into eight groups. Compound Carbomer (0.3%, 0.3 ml) was injected into the left
      anterior chamber. A group of rabbits were randomly killed after 1, 2, 3, 4, 6, 8,
      10 and 12 weeks. The anterior chamber of the rabbit eye specimens was observed.
      RESULTS: IOP increased slowly following the application of the drug, high IOP
      lasted for 3 months. The drug-induced changes of anterior chamber angle consisted
      of early inflammatory response and late fibrous changes. Inflammatory response
      occurred in early stage and reduced or disappeared after 3 weeks. Fibrous
      degeneration and adhesion obstruction occurred in the anterior chamber angle
      after 4 weeks. Under the electron microscope, the trabecular was expanded and
      deformed, with hyperplasia of collagen and elastic fibers. Endothelial cells were
      separated from the trabecular, and showed the morphology of lymphocytes, with the
      function similar to the macrophages. Phagocytized Carbomer particles were
      transported through the vacuoles of Schlemm's canal endothelial cells. Large
      vacuoles gradually reduced. Excessive Carbomer particles were accumulated in the
      endothelial cells and obstructed the Schlemm's canal. This induced the fibrous
      proliferation and the destruction of anterior chamber angle structures.
      CONCLUSIONS: The obstruction of aqueous humor outflow induced by compound
      Carbomer in rabbit high IOP model is caused mainly by the changes in trabecular
      endothelial cells.

PMID- 20137450
TI  - [The effect of phacoemulsification on eyes with preexisting functional filtering
      blebs].
AB  - OBJECTIVE: To investigate the effect of clear corneal phacoemulsification on
      filtering bleb morphology and filtering function in glaucoma eyes with functional
      filtering blebs. Analysis the risk factors of intraocular pressure (IOP)
      increasement after phacoemulsification. METHOD: It was a prospective series case
      study. Twenty-five eyes of 20 Chinese patients who had undergone clear corneal
      phacoemulsification after trabeculectomy were enrolled. IOP and the numbers of
      antiglaucoma medicine before and 1 month, 3 months, 6 months, 12 months and 24
      months after phacoemulsification were recorded. Ultrasound Biomicroscopy was
      conducted preoperatively, 1 month and 24 months postoperatively. Compare the IOP
      and the numbers of antiglaucoma medicines before and after phacoemulsification by
      student t test. Risk factors were evaluated for association with loss of IOP
      control requiring additional medications or further glaucoma surgery, using
      Kaplan-Meier survival analysis. RESULTS: The IOP was (15.8 +/- 5.1) mm Hg (1 mm
      Hg = 0.133 kPa), (13.7 +/- 3.6) mm Hg, (13.6 +/- 3.3) mm Hg, (14.4 +/- 4.1) mm
      Hg, (14.2 +/- 3.6) mm Hg, (13.8 +/- 3.5) mm Hg (P = 0.007, 0.004, 0.021, 0.033,
      0.004) before and at 1, 3, 6, 12, 24 months after phacoemulsification. The
      numbers of antiglaucoma medicine were 0.2 +/- 0.6 and 0.3 +/- 0.7 before and
      after phacoemulsification (P = 0.265). Log-rank analysis the risk factors include
      IOP higher than 15 mm Hg before phacoemusification (P = 0.042), bleb height
      decreased more than 10% 1 month after phacoemusification (P = 0.037) and the
      intrableb reflectivity increase (P = 0.001). CONCLUSIONS: Phacoemulsification on
      eyes with functional filtering bleb did not affect the filtering function. Risk
      factors of loss of IOP control include IOP higher than 15 mm Hg before
      phacoemusification, bleb height decreased more than 10% and the intrableb
      reflectivity increase in a short term after phacoemusification.

PMID- 20137451
TI  - [Preliminary study on normal values of blue-on-yellow perimetry in central thirty
      degrees].
AB  - OBJECTIVE: To investigate the normal values and related factors of blue on yellow
      perimetry (BYP) in the central 30 degree. METHODS: A cross sectional study design
      was performed on this study. BYP was performed in a Humphery750II-i perimetry
      with 30-2 procedure and Fastpac strategy. The study samples consisted of 116 eyes
      of 58 normal subjects. The visual field indices were calculated and their related
      factors were analyzed. SPSS 13.0 software package was used for experiment data
      analysis. Comparison of three blue-on-yellow visual indices, including mean
      sensitivity (MS), mean defect (MD) and pattern standard deviation (PSD), were
      investigated by multi-way ANOVA with randomized block design method among four
      age groups. Relationship between age and visual field index was described and
      interpreted by calculating Pearson product-moment correlation coefficient and
      linear regression. Chi-square test was applied to determine the distribution of
      population and gender among four age groups. Significance level was set to alpha
      = 0.05. RESULTS: Values of the three different visual indices, MS, MD and pattern
      PSD, in central 30 degree of BYP were (21.23 +/- 2.96) dB, (-3.94 +/- 2.20) dB
      and (3.13 +/- 0.72) dB, respectively. The differences of MS, MD and PSD values
      between right eye and left eye were not statistically significant (F = 0.488,
      0.833, and 0.677, with P = 0.487, 0.482 and 0.414, respectively). No differences
      in these three indices could be detected between male and female (F = 0.149,
      0.547 and 1.948, with P = 0.702, 0.463 and 0.169, respectively). Significant
      difference in three visual field indices was identified among four different age
      groups (F = 48.160, 54.250 and 9.329, with P = 0.000, 0.000 and 0.032,
      respectively). The light average sensitivity in four quadrants showed
      statistically significant difference in all age groups (F value for quadrant
      factor was 81.544, P = 0.000). The MS value decreased 2.5 dB and the MD value
      increased -0.932 dB with the 10-year-old increasing. The average sensitivity in
      different eccentric ranges had a significant statistical difference (F value for
      eccentricity factor was 48.257, P = 0.000). CONCLUSIONS: The gender and the
      laterality do not affect the MS, MD and PSD in the BYP of normal subjects. The
      light average sensitivity is asymmetry in the four different quadrant, decreases
      in a linear decline with age and declines with the eccentricity.

PMID- 20137452
TI  - [Observation on changes of anterior chamber and chamber angle structures after
      posterior chamber phakic intraocular lens implantation by ultrasound
      biomicroscopy].
AB  - OBJECTIVE: To study the changes of anterior chamber and chamber angle structures
      after implantable contact lens (ICL) implantation in high myopia by using
      ultrasound biomicroscopy (UBM). METHODS: A prospective series case study was
      conducted on 15 high myopia patients (30 eyes) treated with ICL implant. These
      patients were followed for one year postoperatively. Intraocular pressure (IOP)
      was measured by Goldmann applanation tonometer after surgery. All eyes were
      examined by UBM one year after the surgery. Central anterior chamber depth (ACD),
      trabecular-iris angle (TIA), the distance between the posterior surface of ICL
      and the lens and the distance between peripheral surface of ICL and the lens were
      measured. Nonparametric test was used to compare TIA. One-way ANOVA was used to
      assess the distance between peripheral surface of ICL and the lens. Repeated
      Measure ANOVA and Bonferroni test was performed to compare the IOP level before
      and after surgery. Paired t-test was used to compare ACD. RESULTS: Intraocular
      pressure changed from (13.75 +/- 2.27) mm Hg (1 mm Hg = 0.133 kPa) preoperatively
      to (14.27 +/- 1.70), (14.70 +/- 2.07), (14.07 +/- 2.24), (14.00 +/- 2.69) and
      (13.97 +/- 2.95) mm Hg at 1 week, 1, 3, 6 and 12 months after the surgery,
      respectively. There was a statistically significant increase of the IOP one month
      after the surgery, which was normalized completely at 3 months after surgery. The
      distances between central posterior surface of the cornea to the ICL and the lens
      were (2.24 +/- 0.21) and (2.97 +/- 0.11) mm, respectively. There was significant
      difference between these two data (t = 20.63, P < 0.01). TIA was measured in
      12:00, 3:00, 6:00 and 9:00. There were no statistically differences between them.
      TIA was greater than 30 degree in 55.8% of cases. The distance between the
      central anterior surface of the ICL to the lens (central section) was (0.63 +/-
      0.16) mm. No contact was found between the ICL and the crystalline lens.
      CONCLUSIONS: Posterior chamber phakic intraocular lens implantation for the
      surgical correction of high myopia is a safe procedure as evaluated with
      immediate visual and refractive results. We found that the iridocorneal angle and
      the anterior chamber depth are decreased after the surgery. There is no contact
      between the crystalline lens and ICL. The ICL contacts with the posterior iris
      surface.

PMID- 20137453
TI  - [The accuracy of posterior curvature method in corneal power calculation after
      LASIK surgery].
AB  - OBJECTIVE: To estimate the accuracy of posterior curvature method in corneal
      power calculation after LASIK surgery. METHODS: Corneal power calculation in 11
      eyes that underwent Intraocular Lens (IOL) implantation after LASIK surgery (10
      cases of Phaco + IOL, 1 case of IOL displacement), all of which used posterior
      curvature method, was analyzed retrospectively. The differences between post
      operative stable refraction and target refraction were calculated, the actual
      corneal powers were deduced, and the expected refractive errors using other
      corneal power evaluation methods (auto-keratometry, corneal topography, spherical
      equivalent method, anterior curvature method, Equivalent K Reading method
      provided by Pentacam) were analyzed. In addition, refraction of 23 eyes underwent
      LASIK surgery were done on their 6 months follow-up. The theoretical corneal
      powers were deduced by subtracting the change of refraction before and after
      LASIK surgery from the pre-operative corneal powers. The differences between
      calculated corneal powers using posterior curvature method and the theoretical
      corneal powers were analyzed, and were compared with other corneal power
      evaluation methods. RESULTS: The mean uncorrected post-operative visual acuity of
      IOL implantation eyes using posterior curvature method was 0.8 +/- 0.2, with mean
      absolute refractive error from target of (0.36 +/- 0.36) D (-0.63 to +0.85 D).
      The ratio of eyes with absolute error within 0.25 D, 0.50 D, and 1.00 D was 55%,
      73%, and 91% respectively. This result was significantly lower than that of the
      auto-keratometry (2.50 +/- 1.08) D, corneal topography (1.90 +/- 0.88) D, and
      those obtained from spherical equivalent method (2.09 +/- 1.62) D (P < 0.01) or
      anterior curvature method (1.45 +/- 1.10) D (P < 0.05). It also showed less bias
      (-1.13 to 0.85 D) when compared to the Equivalent K Reading (-1.10 to 1.80 D),
      but the difference was not significant (P > 0.05). For the 23 post LASIK eyes,
      the absolute difference between the corrected corneal power using posterior
      curvature method and theoretical power was (0.67 +/- 0.45) D, also showed least
      bias compared with other methods. CONCLUSION: It is a practical and accurate way
      to calculate the corneal power after LASIK surgery using posterior curvature
      method.

PMID- 20137454
TI  - [The early post-operative wound healing mode study of the rabbit cornea after
      flap-free epiploic laser in-situ keratomileusis].
AB  - OBJECTIVE: To evaluate the wound healing mode of rabbit corneal epithelium after
      Epi-LASIK(epiplolic laser in-situ keratomileusis) and Flap-free Epi-LASIK(Flap
      free epiploic laser in-situ keratomileusis). METHODS: Twenty-four New Zealand
      white rabbits (48 eyes) were randomly divided into four groups. There were six
      rabbits in every group, which were randomly treated with Epi-LASIK in one eye and
      Flap-free Epi-LASIK in the other by VISX20/20 excimer laser. Other three rabbits
      (6 eyes) without any treatment were used as control. The corneal epithelium wound
      healing mode was observed at 1, 2, 4, 7 days after surgery by light microscope
      and electron microscope. The number of keratocytes cells in the central anterior
      stroma were counted by hematoxylin-eosin-stained. The expression of basic
      fibroblast growth factor (bFGF) in corneal stroma were assessed by
      Immunohistochemistry staining. Cornea stromal cell apoptosis was evaluated by
      terminal deoxyribonuc-1-eotidyl transferase-mediated deoxynuridine triphosphate
      nick end labeling (TUNEL) assay.All the data was analysised by t-test to evaluate
      the different of wound healing mode after Epi-LASIK and Flap-free Epi-LASIK.
      RESULTS: The findings of light microscope and electron microscope investigation
      demonstrated that, at the first day after surgery, there was one layer of
      neogenesis of the corneal epithelial cells covering the area of surgery in Flap
      free Epi-LASIK specimens. It would increase gradually after 7 days. At the first
      day after the surgery, the base membrane of the corneal epithelium was tightly
      attached to the stroma in Epi-LASIK specimens. At the second day after the
      surgery, there was edema observed on the epithelium flap in the Epi-LASIK
      specimens. There were more keratocytes cells found at 4 days after surgery in
      Flap-free Epi-LASIK group (33.85 +/- 3.39) than that in Epi-LASIK group (t = 
      2.315, P < 0.05). The expression of bFGF in Flap-free Epi-LASIK group at 2, 4
      days after surgery were 101.75 +/- 8.07 and 110.56 +/- 9.00, which were more than
      Epi-LASIK (t = -2.339, -2.396, P < 0.05). There was less keratocyte apoptosis
      cells in Flap-free Epi-LASIK group than Epi-LASIK group at 2, 4 days after
      surgery (t = 3.332, 2.989, P < 0.05). CONCLUSIONS: Due to the specific way of the
      epithelium removal resulting in the more rapid epithelium healing, the Flap-free
      Epi-LASIK technique is advantageous in reducing the stimulative symptoms after
      the surgery. It's also beneficial for the corneal wound healing.

PMID- 20137455
TI  - [Initial research of customized aberration correction with adaptive optics
      technique].
AB  - OBJECTIVE: To analyze the effects of different wavefront-guided aberration
      ablation patterns on visual function using adaptive optics technique and explore
      the effective and feasible pattern of customized refractive surgery. METHODS:
      Control study. Under dark condition, six volunteers'right eyes were fully dilated
      with 5 g/L phenyl ephedrine. The myopia and astigmatism were first fully
      corrected with optical lens, and then 100% contrast visual acuity of different
      wavefront correction patterns was detected using adaptive optics system in
      through a 6.0 mm pupil optical path. RESULTS: All of the eight different
      aberration correction strategies obtained excellent correction effect. On the
      basis of this correction, visual acuity test was performed. The results showed
      that all aberration correction strategies improved the visual acuity compared
      with static correction. Correction of high order aberrations and full correction
      of aberrations could obtain better visual acuity than that of only correction of
      low order aberrations. Correction of aberrations from second to third order and
      fourth order spherical aberration second only to full correction of aberration.
      CONCLUSION: As for low myopia patients, eliminating ocular high order aberrations
      could improve visual acuity. Correction of aberration from second to third order
      and fourth spherical aberration might be an effective and feasible pattern of
      customized refractive surgery.

PMID- 20137456
TI  - [Analysis of PAX6 gene in a Chinese family with congenital aniridia].
AB  - OBJECTIVE: To explore the pathogenic mutation in a Chinese family with congenital
      aniridia. METHODS: It is a case-control study. All 21 members of the family
      underwent a comprehensive ophthalmic examination and family line investigation.
      Mononuclear cell was isolated from peripheral blood and genomic DNA was prepared
      by genomic DNA purification kit. All fourteen exons of the PAX6 gene were
      amplified by polymerase chain reaction (PCR) from proband's genomic DNA. PCR
      products of each exon were analyzed by direct sequencing. RESULTS: A nonsense
      mutation (Q310X) in exon 11 of PAX6 gene was detected by sequencing analysis in
      the proband III2. This mutation cause the 301st amino acids codon switch from CAA
      to TAA and the codogenic amino acids altered from glutamine glutaminic acid to
      strong terminal codon. This mutation is also detected in all 11 patients of this
      family, but not present in the unaffected members in this family. CONCLUSION: The
      premature translation termination of PAX6 gene caused by a nonsense mutation of
      Q310X should be responsible for congenital aniridia in this Chinese family.

PMID- 20137457
TI  - [Analysis of prognostic factors of retinoblastoma].
AB  - OBJECTIVE: To study the prognostic factors of retinoblastoma (RB). METHODS:
      Prospective case series study.With Envision System, surgical specimens from 31 RB
      cases were immunostained by using anti-NSE, GFAP and S-100 antibodies. Number of
      NSE positive cells was counted at 1000 tumor cells in each slice. The morphology
      of GFAP and S-100 stained positive cells were analyzed. All cases were followed
      up for 5 to 17 years. Cox regression pattern was adopted to analyze the
      relationship between sex, age, stage, differentiation, number of NSE positive
      cells, the sizes of GFAP and S-100 positive cells, therapies and prognosis.
      RESULTS: (1) Almost all cases were stained positively by anti-NSE antibodies.
      Positive rates of GFAP and S-100 expression specimens were 61.29% (19/31) and
      58.06% (18/31), respectively. (2) The number of NSE positive cells was correlated
      with a better prognosis (P = 0.0361). The sizes of GFAP and S-100 stained area
      were also related with a better progress (P = 0.0430, 0.0477). In patients with a
      greater number of NSE stained cells (averaged 324/1000), the survival time was
      >/= 5 years. In patients with a less number of NSE stained cells (averaged
      182/1000), the survival time was less than 5 years. (3) There was a significant
      correlation between the number of NSE stained cells and the results for GFAP and
      S-100 staining (r = 0.547, 0.581), respectively. CONCLUSIONS: The number of NSE
      positive cells is correlated with a better prognosis of RB. The expression of
      GFAP and S-100 protein are also correlated with a better prognosis of RB. The
      number of NSE positive cells and the expression of GFAP and S-100 protein may be
      regarded as the standards in judging the degree of differentiation of RB, and may
      be used as one of criteria for the estimation of the prognosis.

PMID- 20137458
TI  - [Changes of neuroglia cells in human glaucoma and animal model of experimental
      glaucoma].
AB  - Glaucoma is one of the major ocular diseases that lead to blindness. It is
      characterized by optic disk cupping and visual field loss. Glaucoma is a
      multifactorial group of diseases with many different causes but one common
      endpoint, progressive loss of retinal ganglion cells. Hence most studies of
      glaucoma focused on retinal ganglion cells and their nosogenesis. But recent
      studies have showed that neuroglia cells, as another major kind of cells of nerve
      system, also undergo an activation process in glaucoma. Their activation is
      closely connected with the changes of retinal ganglion cells as well as the
      development of the disease. Therefore, more and more attention is focused on the
      changes of these cells. This review is a summary about the recent studies on the
      pathological changes of these four different kinds of neuroglia cells in human
      glaucoma and in several animal models of experimental glaucoma.

PMID- 20137460
TI  - [Discussion on the prevention and control related to influenza from WHO's global
      influenza preplans].

PMID- 20137459
TI  - [Sutureless deep lamellar endothelial keratoplasty].
AB  - Corneal endothelial dysfunction can severely affect visual acuity. In order to
      deal with this morbidity, ophthalmologists used to perform penetrating
      keratoplasty, in which the complications, such as postoperative astigmatism and
      graft rejection, led to poor visual recovery. If only the Descemet's membrane and
      endothelium is transplanted, the corneal injury of recipients caused by surgeries
      would be reduced and better visual acuity recovery might be guaranteed. In the
      past few years, the advantages of sutureless deep lamellar endothelial
      keratoplasty have been brought to the attention by more and more ophthalmologists
      worldwide. However, the challenging techniques of performing DLEK limits its
      clinical application. Other kind of, DSEK, by stripping Descemet's membrane and
      endothelium from the recipient cornea, has produced excellent outcomes. This
      article outlined and analysed surgery techniques, clinical results and
      complications of DSEK.

PMID- 20137461
TI  - [Global vaccine strategy against pandemic influenza].

PMID- 20137462
TI  - [Investigation on a seasonal influenza accompanying with the first locale novel
      A/H1N1 influenza outbreak in China].
AB  - OBJECTIVE: To timely summarize past experience and to provide more pertinent
      reference for control and prevention in A/H1N1 cases in influenza season.
      METHODS: During May 25 to 31, 2009, 2 secondary community cases caused by a
      influenza A/H1N1 imported case. In the close contacts of 3 A/H1N1 cases, 14 had
      some aspirator symptoms onset, such as fever (> or = 37.5 degrees C), cough, sore
      throat and etc. Laboratory tests excluded the infection of A/H1N1 influenza. For
      throat swab test for the 14 cases, 7 were tested for seasonal influenza virus. A
      face-to-face or telephone interview was conducted by CDC staff to collect
      information of 62 close contacts. RESULTS: Of 14 fever cases, there was no
      significant by differences by age[15-age group: 19.2% (5/26), over 25-age group:
      25.0% (9/36); chi(2) = 0.287, P = 0.592]; by sex group [24.0% (6/25) for male and
      21.6% (8/37) for female; chi(2) = 0.048, P = 0.826], by working units [dressing
      and design, photograph, saleroom and others, consumer group: 42.1% (8/19), 27.3%
      (3/11), 12.5% (2/16) and 6.3% (1/16); chi(2) = 7.653, P = 0.054], by dormitory
      style [dormitory style = 33.3% (4/12), non-dormitory style = 29.4% (10/34);
      chi(2) = 0.699, P = 0.403]. All the cases had fever (37.5 - 37.9 degrees C), no
      case had diarrhea. One in 3 A/H1N1 cases had diarrhea. All the 14 cases were
      negative result for A/H1N1 RNA. Six from 7 cases were positive for seasonal
      influenza test. CONCLUSION: This was a seasonal influenza outbreak happened in
      the close contacts of first confirmed A/H1N1 cases in community in mainland
      China. It showed that we should exclude the seasonal influenza in the
      investigation of A/H1N1 cases in the seasonal influenza period in some time. It
      is necessary to take effective measure to strengthen the control and prevention
      of seasonal influenza.

PMID- 20137463
TI  - [Type A/H1N1 influenza: a clinical summary of 24 imported cases].
AB  - OBJECTIVE: To study the clinical characteristics and laboratory results of 24
      confirmed H1N1 influenza cases. METHODS: The characters of clinical, laboratory,
      iconography and etiology of 24 patients with A/H1N1 were studied, and the changes
      of T-lymphocyte subsets that between the pre- and post-treatment were evaluated.
      RESULTS: The ages of patients were ranged from 6 to 65 years old; average age was
      26 years old.15 patients were under 25 years old. 22 (22/24, 91.7%) patients had
      recently traveled to USA or Canada. The most common presenting symptoms were:
      fever (22/24, 91.7%); sore throat (22/24, 91.7%); cough (20/24, 83.3%); dry cough
      (14/24, 58.3%); expectoration (6/24, 25.0%); nasal discharge (6/24, 25.0%). Six
      had pneumonia in sixteen patients (6/16, 37.5%) who took CT scan; seven (7/24,
      29.2%) had headache and four (4/24, 16.7%) had muscular soreness; two (2/24,
      8.3%) had sneeze and nasal obstruction; only one(1/24, 4.2%) had diarrhea; one
      (1/24, 4.2%) had conjunctivitis. The result of 23 patients about T-Lymphocyte
      subsets: most of CD4 and CD8 were decreased (18/23, 78.3%), ranging from 122 to
      691 cells/microl (normal was 706 - 1125 cells/microl), with the average of 408
      cells/microl, but ratios of CD4/CD8 were normal. Fourteen patients were detected
      CD4 and CD8 after received the treatment during 5 to 7 days.the results of CD4
      (cells/microl) were different between the pre- and post-treatment: 436.29 +/-
      189.06, 976.71 +/- 332.96 (paired-samples t test: t = -5.416, P < 0.05) while the
      results of CD8 (cells/microl) were: 323.64 +/- 176.47, 703.14 +/- 211.77 (t = 
      5.319, P < 0.05); the results of leukocytes in 22 patients were different between
      pre- and post-treatment: (5.13 +/- 1.47) x 10(9)/L, (6.25 +/- 1.37) x 10(9)/L (t
      = -2.900, P < 0.05) while the results of lymphocytes were: (1.16 +/- 0.43) x
      10(9)/L, (2.30 +/- 0.37) x 10(9)/L (t = -6.819, P < 0.05); but the ratios of
      CD4/CD8 were: 1.44 +/- 0.41, 1.40 +/- 0.26 (t = 0.507, P > 0.05). All the
      patients were received antivirus treatment (Oseltamivir) and the virus conversed
      during 1 - 10 days (average 4.5 days). The temperature was normal after onset
      during 3 - 4 days and the patients were recovered during 3 - 13 days (with the
      average of 7.3 days). CONCLUSION: Influenza A virus H1N1 subtype was identified
      as the cause of outbreaks of febrile respiratory infection which was self
      limited. There was no evidence to show that the changes of T-Lymphocyte subsets
      could indicate the prognosis of patients.

PMID- 20137464
TI  - [Epidemiological and molecular characterization of seasonal influenza A/H3N2
      viruses circulating in Shenzhen, 2005 - 2007].
AB  - OBJECTIVE: To determine the epidemiological characteristics of seasonal influenza
      in Shenzhen from 2005 to 2007 and the molecular variation of HA1 domain of
      influenza H3N2 viruses. METHODS: The consultation rate for influenza-like illness
      (ILI) were calculated weekly for indicating the influenza activities (the
      Shenzhen Influenza Surveillance System mainly consisted of 16 institutions with 9
      hospitals, 6 districts and one municipal centers of disease control and
      prevention). Pharyngeal swabs from the cases of ILI, which were collected during
      2005 to 2007 from the city-wide and quality-controlled surveillance network, were
      used to propagate the viruses. The HA1 region of the influenza A/H3N2 viruses
      were detected by RT-PCR and sequenced subsequently. The analyses of pairwise
      amino acid variations, genetic clustering and phylogenetics was performed.
      RESULTS: The activity levels of influenza showed certain changes during each year
      from 2005 to 2007, and there were summer peaks from May to July in 2006 and 2007.
      The positive rates of influenza virus were 4.78% (114/2385), 5.77% (212/3674) and
      12.12% (343/2831) from 2005 to 2007 respectively. The weekly isolating rates
      changed accordingly with the trend of the percentages of ILI. The proportions of
      influenza H3N2 virus were 25.46% (28/114) and 2.83% (6/212) in 2005 and in 2006
      respectively, but the proportion increased to 62.68% (215/343), which indicated
      that H3N2 virus became the predominant strain in 2007. Phylogenetic clustering
      analysis of influenza H3N2 virus revealed that there were 5 clades. The viruses
      which were isolated in 2005 contained in the clade I and II, the viruses in 2006
      were comprised in clade III, and clade IV and V included the viruses isolated in
      2007. Although the stem of cladogram developed with one accord of the time
      isolated viruses, the viruses which were similar to vaccine strains had
      circulated in Shenzhen before a given strain was determined as vaccine strain by
      WHO. It was also noticed that more amino acid changes at antigenic sites,
      especially at sites A and B in the H3N2 viruses, were found in 2007 than that in
      2005 and in 2006. But the sequences at the receptor-binding sites and disulphide
      bond sites were conserved and no new circulating strain for genetic reassortment
      had been found in the period. CONCLUSION: Shenzhen might be one of areas where
      the ongoing genetic drift of influenza H3N2 viruses appeared earlier in China.
      The changes of influenza H3N2 virus showed the active status in the population.
      The results suggested that monitoring seasonal influenza viruses by sequence
      analysis could provide important and timely information on the appearance of
      strains with epidemiologic significance.

PMID- 20137465
TI  - [An etiological study on acute respiratory infection among inpatient children in
      Suzhou].
AB  - OBJECTIVE: To investigate the pathogen of children with acute respiratory
      infection (ARI) in Suzhou and to provide some evidences for clinical diagnosis
      and treatment. METHODS: The nasopharyngeal secretion samples from 2492 inpatient
      children with ARI, during the period of November 2005 to May 2007, were
      investigated for respiratory syncycial virus (RSV), influenza virus A and B,
      parainfluenza virus type 1, 2, 3 and adenovirus by both the indirect
      immunofluorescence assay and virus isolation. Human metapneumovirus (hMPV) were
      examined by reverse-transcription polymerase chain reaction (RT-PCR) at the same
      time. RESULTS: Of 2492 samples tested, 961 (38.6%) were positive. The total
      positive rate of virus pathogens in children with ARI was found related to age,
      season and respiratory disease. The detection rates by age were: 50.0% (412/824),
      43.4% (190/438), 30.5% (207/679)and 27.6% (152/551), chi(2) = 96.5002, P < 0.01;
      the detection rates by season were : 46.7% (366/784), 13.8% (66/478), 13.8%
      (59/428) and 58.6% (470/802), chi(2) = 392.3279, P < 0.01; the detection rates by
      disease were (acute upper respiratory infection, acute laryngitis, throat-trachea
      bronchitis, bronchial pneumonia, pneumonia genuine, bronchiolitis, bronchial
      asthma): 21.4% (30/140), 73.7% (14/19), 32.0% (8/25), 36.9% (598/1620), 13.1%
      (8/61), 66.1% (216/327) and 29.0% (87/300), chi(2) = 162.1276, P < 0.01. There
      was no association between the total positive rate and sex. The detection rates
      by sex were: 39.0% (588/1508) for male and 37.9% (373/984) for female, chi(2) =
      0.2962, P > 0.05. The peak of RSV appeared from December to March. There was the
      highest RSV detection rate 50.2% (164/327) with bronchiolitis. The hMPV can be
      detected all year around. The peak of hMPV appeared in winter and the detection
      rate was 13.2% (106/802). CONCLUSION: RSV and hMPV are the main respiratory viral
      pathogens in Suzhou. Detection of viral pathogens in children with respiratory
      infection could give fast, accurate diagnostic evidence, and help avoid
      antibiotics abuse.

PMID- 20137466
TI  - [The etiology and clinical manifestations of 70 patients with hand-foot-mouth
      disease].
AB  - OBJECTIVE: To analyze the etiology and clinical manifestations of 70 patients
      with hand-foot-mouth disease (HFMD). METHODS: The viral RNA from the pharynx swab
      samples were extracted and collected from 70 HFMD patients (of which, 60 cases
      were under 5 years old) to detect the 5'-UTR gene of EV, the Vp3-Vp1 genes of
      EV71 and Cox-A16 by utilizing the technique of RT-PCR. RESULTS: Of 70 HFMD
      patients, 30 cases (42.8%, 30/70) were positive in enterovirus nucleic acid,
      including EV71 and Cox-A16, pharynx swab sample testing. While, of the
      enteroviral pathogen RNA-positive 30 cases, EV71 accounted for 66.7% (20/30). The
      proportion of etiological positive of 39 samples collected within 4 days after
      onset was 66.7% (26/39), but the probability of 31 samples collected after more
      than 5 days after onset was 12.9% (4/31), the difference was significantly
      (chi(2) = 20.4, P < 0.01). CONCLUSION: HFMD patients were mainly infants and
      young children between 0-5 years old, but adults could also be attacked. The
      enterovirus detected was mainly EV71, and the pharynx swab samples should be
      collected within 4 days after onset to increase the related viral nucleic acid
      positive detection probability.

PMID- 20137467
TI  - [Incidence trends of colorectal cancer in urban Shanghai, 1973 - 2005].
AB  - OBJECTIVE: To explore the time trends of colorectal cancer incidence rates in
      urban Shanghai from 1973 to 2005. METHODS: Data on the incidence rates of
      colorectal cancer were obtained from a population-based cancer registry in
      Shanghai. A total of 32 962 colon cancer patients and 24 662 rectal cancer
      patients were registered. Population estimation were based on periodic censuses,
      with age- and sex-specific annual estimates derived for the remaining years. The
      rates were adjusted to the world standard population by using the direct method.
      Annul percent changes (APCs) in rates were estimated by means of a linear
      regression of the logarithm of the respective rates on calendar, weighted by the
      number of incidence cases. RESULTS: The incidence rates of colorectal cancer
      increased steadily during 1973 to 2005, the age-adjusted incidence rates of colon
      cancer increased from 6.09 and 5.70 to 14.70 and 14.35 per 100 000 in male and
      female respectively. The APCs were 3.03% (t = 14.77, P < 0.01) and 3.21% (t =
      22.15, P < 0.01). The rates of rectal cancer increased from 7.68 and 6.51 to
      11.45 and 8.28 per 100 000 in male and female respectively. The APCs were 1.34%
      (t = 7.28, P < 0.01) and 0.93% (t = 7.34, P < 0.01). The top APCs for colon and
      rectal cancer in female were 5.86% and 2.79% at age above 85 and in male those
      were 4.64% and 2.38% at age of 80-. The APCs of colon cancer were greater than
      those of rectal cancer at the groups above 45 years old. The average ages when
      diagnosed were delayed from 57 - 60 to 66 - 70 during these 33 years. The average
      diagnosed ages of colon cancer were later than those of rectal cancer slightly
      (from 2003 to 2005, the onset age of male colon cancer: 68.61 +/- 12.17, male
      rectal cancer: 66.81 +/- 12.62, t = 4.90, P < 0.01; female colon cancer: 69.20 +/
      12.13, female rectal cancer: 67.75 +/- 12.54, t = 3.81, P < 0.01). CONCLUSION:
      The incidence rates of colorectal cancer increased steadily during 1973 to 2005,
      especially for colon cancer. Further research is needed to identify the causes
      resulting in these changes.

PMID- 20137468
TI  - [Health care status of female workers exposed to occupational hazards in Haidian
      district of Beijing].
AB  - OBJECTIVE: To investigate the health care status of female workers exposed to
      occupational hazards in Haidian district of Beijing and improve the labor
      protection of female workers. METHODS: A questionnaire provided by National
      Center for Women and Children's Health of Chinese CDC was used in the survey
      conducted to collect information about health care status of female workers in
      141 factories with occupational hazards including chemical poisons and physical
      factors (noise, libration, microwave, high frequency and low temperature).
      RESULTS: 141 factories were investigated, including 53 state-owned enterprises,
      21 collective enterprises, 46 joint-stock enterprises, and 21 non-public
      enterprises. 12 251 female workers were surveyed, 10.19% (1249/12 251) of whom
      were exposed to occupational hazards. Of 141 factories studied, 16.31% (23/141)
      had no labor protection management organization.27.66% (39/141) did not provide
      pre-employment physical examination service to female workers.48.94% (69/141)
      didn't establish labor protection system for female workers in menstrual period.
      While, 21.28% (30/141) of the studied institutes deducted some salaries in the
      pregnancy, and 32.62% (46/141) deducted their wages during the puerperal period.
      2.13% (3/141) arranged female workers in the posts which are forbidden by law
      (continuous heavy work load operation).9.93% (14/141) arranged pregnant female
      workers on the post forbidden by law.31.91% (45/141) and 33.33% (47/141) would
      deduct the time of prenatal medical examination and lactation from their working
      hours, respectively.39.01% (55/141) didn't afford the cost of fertility. 68.09%
      (96/141) had annual gynecological examination.45 factories were collected
      occupational examination reports, accounted for 31.91% (45/141). No female
      workers were found suffering from occupational disease. Of the 1865 occupational
      hazard factor monitoring points in 34 factories, there were 155 monitoring
      points, which were all noise monitoring points, did not meet the standard.
      CONCLUSION: The current health-care status of female workers is not optimistic.
      It is necessary to consistently improve health care legislations, establish
      coordinated management mechanism and strengthen the publicity of policy to
      protect female workers.

PMID- 20137469
TI  - [Effects of indole-3-carbinol on the outcome of tumor and the changes of anti
      oxidative system in null mice grafted with nasopharyngeal carcinoma].
AB  - OBJECTIVE: To observe the effects of indole-3-carbinol (I3C) on the outcome of
      the tumor as well as the changes of the anti-oxidative system in null mice
      grafted with nasopharyngeal carcinoma. METHODS: 48 BALB/c null mice were divided
      by means of random number table into control group (0.5% sodium carboxyl methyl
      cellulose), low dosage (0.02 g/kg), middle dosage (0.1 g/kg) and high dosage (0.5
      g/kg) of I3C. The mice were administered with different solutions by gavage for
      10 days before CNE1 cells were inoculated subcutaneously into the back (near the
      armpit) of the nude mice, then the solutions were continually administered by
      gavage. The tumor volume was measured and the tumor inhibitory rate was
      calculated. The level of malondialdehyde (MDA), the activity of superoxide
      dismutases (SOD), the activity of glutathione peroxidase (GSHPx) and the
      expression of cleaved caspase-3 were determined on the 31th day of the study.
      RESULTS: I3C could reduce the tumor volume [the tumor volumes of the control
      group, the middle dosage group and the high dosage group were (4.13 +/- 0.53) x
      10(-6) m(3), (3.14 +/- 0.71) x 10(-6) m(3), (2.72 +/- 0.29) x 10(-6) m(3)], as
      compared with the control, the shrinkage of tumor volume of the middle dosage
      group and the high dosage group were significant (the t valued at 0.990 and
      1.510, P < 0.01). The tumor inhibitory rates of 3 groups were 3.8%, 20.5% and
      34.9%, respectively. The contents of MDA in the tumor tissue tended to decrease
      [the values of control group, the low dosage group, the middle dosage group and
      the high dosage group were (31.29 +/- 2.51) x 10(-6) mol/L, (30.12 +/- 2.37) x
      10(-6) mol/L, (23.32 +/- 1.93) x 10(-6) mol/L, (16.45 +/- 1.43) x 10(-6) mol/L]
      (F = 98.752, P < 0.01), and that of the high and the middle dosage group could
      obviously be reduced (t = 8.970, 14.840, P < 0.01) as compared with the control.
      The activity of SOD seemed to be elevated according to the increase of I3C dosage
      [the values were (387.24 +/- 23.16) x 10(3) U/L, (399.37 +/- 34.45) x 10(3) U/L,
      (431.63 +/- 31.24) x 10(3) U/L, (476.45 +/- 44.67) x 10(3) U/L] (F = 53.444, P <
      0.01). When compared with the control, the SOD activity of the middle and the
      high dosage group be obviously increased (t = 44.390, 89.210, P < 0.01). I3C
      could also elevate the GSHPx activity [the GSHPx values of the four groups were
      (226.98 +/- 18.35) x 10(3) U/L, (234.65 +/- 15.59) x 10(3) U/L, (247.72 +/-
      22.73) x 10(3) U/L, (300.37 +/- 26.02) x 10(3) U/L] (F = 25.916, P < 0.01). The
      GSHPx of the high dosage group was enhanced remarkable (t = 73.390, P < 0.01) as
      compared with the control. The expression of cleaved caspase-3 (relative
      molecular weight = 19 000 000) seemed to be elevated according to the increase of
      I3C dosage and the relative expression levels of which were 0.87 +/- 0.01, 0.97
      +/- 0.01, 1.02 +/- 0.06 and 1.14 +/- 0.02 (F = 39.864, P < 0.01). When compared
      with the control, the elevation of this kind of cleaved caspase-3 was considered
      statistical significant (the t values were 0.100, 0.086 and 0.303, respectively,
      P < 0.05). When I3C dosage increased, the expression of cleaved caspase-3
      (relative molecular weight = 17 000 000) seemed to increased too [the relative
      expression levels of which were 0.00 +/- 0.00, 0.05 +/- 0.02, 0.11 +/- 0.02, 0.20
      +/- 0.02 (F = 56.629, P < 0.01)], and the increase of this kind of cleaved
      caspase-3 was esteemed significantly as compared with those of the control (the t
      valued at 0.046, 0.103 and 0.193, respectively, P < 0.05). Linear correlate
      analysis showed that the correlation coefficients between the shrinkage of tumor
      volume and the expression of the two kinds of cleaved caspase-3 protein was 
      0.732 (t = 3.404, P < 0.01) and -0.901 (t = 6.642, P < 0.01). CONCLUSION: I3C
      could reduce the growth of tumor, the mechanism underlie it could be related to
      the decrease of the content of MDA as well as the elevated levels of SOD, GSHPx,
      and perhaps could be related to the apoptosis transduced by cleaved caspase-3.

PMID- 20137470
TI  - [Development of a universal primers PCR-coupled liquid bead array to detect
      biothreat bacteria].
AB  - OBJECTIVE: To develop a fast, high-throughput screening method with suspension
      array technique for simultaneous detection of biothreat bacteria. METHODS: 16 S
      rDNA universal primers for Bacillus anthracis, Francisella tularensis, Yersinia
      pestis, Brucella spp.and Burkholderia pseudomallei were selected to amplify
      corresponding regions and the genus-specific or species-specific probes were
      designed. After amplification of chromosomal DNA by 16 S rDNA primers 341A and
      519B, the PCR products were detected by suspension array technique. The
      sensitivity, specificity, reproducibility and detection power were also analyzed.
      RESULTS: After PCR amplification by 16 S rDNA primers and specific probe
      hybridization, the target microorganisms could be identified at genus level,
      cross reaction was recognized in the same genus. The detection sensitivity of the
      assay was 1.5 pg/microl (Burkholderia pseudomallei), 20 pg/microl (Brucella
      spp.), 7 pg/microl (Bacillus anthracis), 0.1 pg/microl (Francisella tularensis),
      and 1.1 pg/microl (Yersinia pestis), respectively. The coefficient of variation
      for 15 test of different probes was ranged from 5.18% to 17.88%, it showed good
      reproducibility. The assay could correctly identify Bacillus anthracis and
      Yersinia pestis strains in simulated white powder samples. CONCLUSION: The
      suspension array technique could be served as an opening screening method for
      biothreat bacteria rapid detection.

PMID- 20137471
TI  - [The effect of soy isoflavones on ATP binding cassette A1 expression level in
      rats without ovaries with atherosclerotic plaque].
AB  - OBJECTIVE: To study the effect of soy isoflavones (SI) on ATP binding cassette A1
      (ABCA1) expression in rats without ovary with atherosclerosis. METHODS: After
      they were raised for a week by given basic feed, the ovaries of 50 12-week old
      SPF rats were removed. The rats were randomly divided into groups by weight. Ten
      rats were selected as the basic control group (A) that basic feed was given all
      through the research. The other 40 rats were given high-fat diets and at the end
      of 4 weeks, these rats were randomly divided into four groups by blood lipid
      level: atherosclerotic model group (B) that was given high-fat diets through the
      research, low isoflavones group (C) that was given high-fat diets plus 30 mg/kg
      SI, middle isoflavones group (D) that was given high-fat diets plus 90 mg/kg SI,
      and high isoflavones group (E) that was given high-fat diets plus 270 mg/kg SI.
      After 22 weeks, all rats were executed to measure morphological change on the
      aorta wall, assessing the ABCA1 gene expression in aorta wall by real-time PCR
      and protein expression by Western blotting in aorta wall, small intestine and
      liver. RESULTS: Serum lipid level of A, B, C, D, E groups: TC levels were (6.82
      +/- 0.22), (15.73 +/- 1.51), (10.77 +/- 1.12), (9.95 +/- 1.18), (9.11 +/- 1.12)
      mmol/L respectively (F = 72.882, P < 0.01); TG levels were: (2.49 +/- 0.24),
      (0.78 +/- 0.13), (0.39 +/- 0.08), (0.29 +/- 0.09), (0.24 +/- 0.09) mmol/L
      respectively (F = 378.515, P < 0.01); LDL-C levels were (1.29 +/- 0.08), (14.76
      +/- 1.23), (8.18 +/- 0.80), (7.85 +/- 0.72), (7.16 +/- 0.64)mmol/L respectively
      (F = 320.936, P < 0.01); HDL-C levels were (1.94 +/- 0.18), (1.04 +/- 0.10),
      (1.55 +/- 0.14), (1.88 +/- 0.17), (2.11 +/- 0.22) mmol/L respectively (F =
      49.450, P < 0.01). ABCA1 protein expression in intestine, liver and aorta: for A,
      B, C, E groups in intestine were 96.577 +/- 9.743, 5.218 +/- 2.048, 18.060 +/-
      5.179, 54.725 +/- 8.960, respectively (F = 172.272, P < 0.01); ABCA1 protein
      expression in liver of groups of A, B, C, E were: 13.657 +/- 2.397, 1.361 +/-
      0.266, 7.069 +/- 2.264, 11.793 +/- 2.515 respectively (F = 37.383, P < 0.01);
      ABCA1 protein expression in aorta of groups A, B, C, E were: 6.756 +/- 1.310,
      0.027 +/- 0.006, 0.035 +/- 0.002 and 7.479 +/- 1.520 respectively (F = 91.999, P
      < 0.01). Compared to basic control group, atherosclerotic plaque could be
      observed in atherosclerotic model group, and it could be partially reversed by
      isoflavones addition. CONCLUSION: Soy isoflavones treatment might inhibit
      atherosclerotic progression by lowering the level of blood lipid and increasing
      ABCA1 expression.

PMID- 20137472
TI  - [Study on the automatic ribotyping for Enterobacter sakazakii].
AB  - OBJECTIVE: To analyze the ribotyping fingerprint of Enterobacter sakazakii (E.
      sakazakii) isolated from food and its typing power. METHODS: Two standard strains
      and twenty-eight isolates of E.sakazakii were analyzed by the DuPont
      Riboprinter(TM) microbial characterization system. The relevant database was
      established and the fingerprint patterns were analyzed with BioNumerics software.
      RESULTS: This system grouped two standard strains and twenty-eight E.sakazakii
      isolates into 26 ribotypes, and four ribotypes included two strains respectively,
      the other twenty-two strains showed different ribotypes. The lowest similarity
      was 31.58%. The number of bands by ribotyping was approximately ten and the
      molecular weight of these bands ranged from 1 to 50 kb. By the clustering program
      in BioNumerics, these isolates could be grouped into four clusters. CONCLUSION:
      The automatic ribotyping method is convenient and fast in E.sakazakii typing.

PMID- 20137473
TI  - [The immunogenicity and safety of 10 microg recombination yeast hepatitis B
      vaccine applied in expanded population].
AB  - OBJECTIVE: To assess the feasibility of the 10 microg recombination yeast
      hepatitis B vaccine in the expanded applicable population group aged 5 - 18.
      METHODS: People with both HBsAg and anti-HBs negative were selected to take two
      stage clinical experiment and the safety and immunogenicity were observed. Safety
      observation was conducted in 925 subjects, while 568 for immunogenicity. The
      observation group (aged 5 - 18) included 493 subjects, and (age > 18) 75 enrolled
      in control group. For the observation group, there were three sub-groups
      including a child group (141, aged 5 - 6), early youth group (177, aged 12 - 13),
      and youth group (175, aged 16 - 18). Both groups were administered with 10 microg
      recombination yeast hepatitis B vaccines with 3 doses at 0 month, 1st month, 6th
      month. To assess the immunogenicity, the vaccination reactions were observed
      during the following 4 weeks in order to assess the vaccine safety. The blood
      samples were taken during 4 - 6 weeks after fully vaccinated, and then anti-HBs
      were tested with RIA and analyzed by comparing the positive rate of anti-HBs, the
      geometric mean titer (GMT) and the protective rate between the two groups.
      RESULTS: Both observation and control group didn't show any general reactions,
      adverse events following immunization (AEFI) or coincidental cases when observed
      at 0.5 h, 6 h, 24 h, 48 h, 72 h, 1 week, 2 weeks, 3 weeks, 4 weeks after being
      vaccinated. The result of serum test showed, the positive rates of child group,
      early youth group, youth group and control group were respectively 100.00%
      (141/141), 97.18% (172/177), 98.29% (172/175) and 89.33% (67/75); the GMTs of
      anti-HBs were respectively 440.28, 875.38, 467.80, 131.06 U/L; the protective
      rates were respectively 100.00% (141/141), 97.18% (172/177), 97.14% (170/175) and
      86.67% (65/75). The positive rate, GMT and protective rate of the experimental
      group were all higher than that of control group (chi(2)(positive rate) = 12.77,
      5.12, 7.99; t(GMT) = 3.89, 4.13, 5.91; chi(2)(protective rate) = 16.81, 8.60,
      8.44; P < 0.05). CONCLUSION: This vaccine could be expanded to 5 - 18 year-old
      population with safety and effectiveness, the positive rate and protective rate
      of anti-HBs were both higher than that of control group.

PMID- 20137474
TI  - [Correlates of bronchial asthma in Uygur and Han adults in Turpan prefecture,
      Xinjiang].
AB  - OBJECTIVE: To analyze possible difference in bronchial asthma between ethnic and
      geographic groups and explore its correlates among Uygur and Han adults in Turpan
      Prefecture, Xinjiang. METHODS: One hundred and sixty-six clinically diagnosed
      asthmatic patients at Turpan Prefecture Hospital, Xinjiang, 86 of Uygur and 80 of
      Han ethnic, and 166 1:1 matched controls from ophthalmological outpatient
      department at the same hospital were recruited into the study. Interview with
      questionnaire was conducted and serum levels of eosinophilic cation protein (S
      ECP), total IgE (T-IgE) and specific IgE (S-IgE) were measured for all of the
      participants to study related factors for asthma with univariate and multivariate
      conditional logistic regression analyses. RESULTS: Bronchial infection (OR(U) =
      5.111, 95%CI: 1.203 - 21.710; OR(H) = 2.498, 95%CI: 1.471 - 5.069), family
      history of asthma (OR(U) = 3.078, 95%CI: 1.812 - 5.188; OR(H) = 2.711, 95%CI:
      1.010 - 6.176), personal allergy history (OR(U) = 2.083, 95%CI: 1.043 - 4.162;
      OR(H) = 3.998, 95%CI: 1.739 - 9.198), weather change (OR(U) = 2.218, 95%CI: 1.199
      - 3.778; OR(H) = 1.733, 95%CI: 1.004 - 2.994) and positive S-IgE (OR(U) = 1.592,
      95%CI: 1.018 - 2.491; OR(H) = 3.858, 95%CI: 2.246 - 8.507) correlated with asthma
      in patients of both Uygur and Han ethnic. Percentage of asthma attack induced by
      respiratory infection [59.30% (51/86)] and weather change [36.05% (31/86)] in
      Uygur patients was significantly higher than that in Han ethnic [42.50% (34/80)
      and 21.25% (17/80), respectively], but percentage of those with personal allergy
      history [48.75% (39/80)] and positive S-IgE [52.50% (42/80)] in Han ethnic was
      significantly higher than that in Uygur [32.56% (28/86) and 30.23% (26/86),
      respectively]. Levels of S-ECP and T-IgE in patients with moderate and severe
      asthma of both Uygur and Han ethnic [(S-ECP(U) = 7.95 +/- 3.98) microg/L, S
      ECP(H) = (11.21 +/- 4.74) microg/L, T- IgE(U) = (72.23 +/- 45.92) kU/L, T-IgE(H)
      = (108.81 +/- 64.07) kU/L, respectively]were significantly higher than those in
      controls of the same ethnic [S- ECP(U) = (1.94 +/- 1.16) microg/L, S-ECP(H) =
      (2.07 +/- 1.63) microg/L, T-IgE(U) = (46.19 +/- 32.47) kU/L, T-IgE(H) = (50.97 +/
      38.51) kU/L; t values were 8.96, 10.52, 2.81, 4.97, P < 0.01], higher in Han
      ethnic than those in Uygur (t values were 3.01, 2.68, P < 0.01). CONCLUSION:
      Bronchial infection, family asthma history, personal allergy history, weather
      change and positive S-IgE all were important correlates of asthma in Turpan
      Prefecture, Xinjiang. Levels of S-ECP and T-IgE in patients with moderate and
      severe asthma increased during its attacks, higher in Han ethnic than those in
      Uygur. Genetic and environmental factors may be involved in occurrence and
      development of asthma.

PMID- 20137475
TI  - Prevention of hepatitis B in China: achievements and challenges.

PMID- 20137476
TI  - Low-dose amiodarone for the prevention of atrial fibrillation after coronary
      artery bypass grafting in patients older than 70 years.
AB  - BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmia after
      coronary artery bypass grafting (CABG), which not only increases the suffering of
      the patients, but also prolongs hospital stay and enhances cost of care,
      especially for patients older than 70 years. This study was designed to evaluate
      the efficacy and safety of low-dose amiodarone in the prevention of AF after
      CABG, especially for the elderly. METHODS: Two hundred and ten senile patients
      undergoing off-pump CABG were included in this prospective, randomized, double
      blind and placebo controlled study. Patients were given 10 mg/kg of amiodarone
      (low-dose amiodarone group, n = 100) or placebo (control group, n = 110) daily
      for 7 days before surgery and followed by 200 mg of amiodarone or placebo daily
      for 10 days postoperatively. RESULTS: Postoperative AF occurred in 16 patients
      (16%) receiving amiodarone and in 36 (37.7%) patients receiving placebo (P =
      0.006). AF occurred at (58.13 +/- 16.63) hours after CABG in the low-dose
      amiodarone group and at (45.03 +/- 17.40) hours in the control group (P = 0.018).
      The maximum ventricular rate during AF was significantly slower in the low-dose
      amiodarone group ((121.42 +/- 28.91) beats/min) than in the control group
      ((134.11 +/- 30.57) beats/min, P = 0.036). The duration of AF was (10.92 +/-
      9.56) hours for the low-dose amiodarone group compared with (14.81 +/- 10.37)
      hours for the control group (P = 0.002). The postoperative left ventricular
      ejection fraction (LVEF) was significantly improved in the low-dose amiodarone
      group (from (59.9 +/- 10.3)% to (63.4 +/- 11.4)%, P = 0.001), and significantly
      higher compared with the control group ((58.5 +/- 10.7)%, P = 0.002). Both groups
      had a similar incidence of complication other than rhythm disturbances (12.0% vs
      16.4%, P = 0.368). The low-dose amiodarone group patients had shorter hospital
      stays ((11.8 +/- 3.2) days vs (13.8 +/- 4.7) days, P = 0.001) and lower cost of
      care (RMB (79 115 +/- 16 673) Yuan vs RMB (84 997 +/- 21 587) Yuan, P = 0.031)
      than that of control group patients. The in-hospital mortality was not
      significantly different between the two groups (1.0% vs 0.9%, P = 0.946).
      CONCLUSIONS: Perioperative low-dose oral amiodarone appeared to be cost-effective
      in the prevention and delay of new-onset postoperative AF in aged patients. It
      significantly reduced ventricular rate and duration of AF after CABG, decreased
      hospital cost and stay, as well as promoted the amelioration of left ventricular
      systolic function. Furthermore, low-dose amiodarone was safe to use and well
      tolerated with low toxic and side effects, and did not increase the risk of
      complications and mortality. It is proved to be a first-line therapy and as
      routine prophylaxis for AF after CABG, especially for elderly patients
      complicated with left ventricular dysfunction.

PMID- 20137477
TI  - A randomized, multicenter controlled trial to compare the efficacy of recombinant
      human parathyroid hormone (1-34) with elcatonin in postmenopausal women with
      osteoporosis in China.
AB  - BACKGROUND: Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) given by
      injection is a new seventh class drug of biological products, which is prepared
      by adopting gene recombination technique. rhPTH (1-34) is mainly used to treat
      osteoporosis, especially for postmenopausal women. This study compared the
      clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating
      postmenopausal women with osteoporosis in 11 urban areas of China. METHODS: Two
      hundred and five women with osteoporosis were enrolled in a 6-month, multicenter,
      randomized, controlled study. They were randomized to receive either rhPTH (1-34)
      20 microg (200 U) daily or elcatonin 20 U weekly. Lumbar spine (L1-4) and femoral
      neck bone mineral density (BMD), as well as biochemical markers of bone turnover
      were measured. Adverse events were recorded. RESULTS: rhPTH (1-34) increased
      lumbar BMD significantly more than did elcatonin at 3 months and 6 months (2.38%
      vs 0.59%, P < 0.05; 5.51% vs 1.55%, P < 0.01), but there were no significant
      increases of BMD in these two groups at femoral neck. There were larger mean
      increases in bone markers in the rhPTH (1-34) group than in the elcatonin group
      at 3 months and 6 months (serum bone-specific alkaline phosphatase (BSAP) 36.79%
      vs 0.31%; 92.42% vs -0.17%; urinary N-telopeptide/creatinine (NTX/Cr) 48.91% vs 
      5.32%; 68.82% vs -10.86%). Both treatments were well tolerated and there were no
      significant differences detected between the two groups in the proportion of any
      adverse events and any serious adverse events (67.0% vs 59.0%; 0 vs 0).
      CONCLUSIONS: rhPTH (1-34) has more positive effects on bone formation, as shown
      by the larger increments of lumbar BMD and bone formation markers, than
      elcatonin, with only mild adverse events and no significant change in the liver,
      kidney or hematological indices.

PMID- 20137478
TI  - The cross-sectional and longitudinal association of the BODE index with quality
      of life in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: The body mass index, airflow obstruction, dyspnea, and exercise
      capacity (BODE) index was shown at predicting the risk of death, exacerbation and
      disease severity among patients with COPD, but few studies verified relationship
      between BODE index and health related quality of life (HRQoL) among Chinese COPD
      patients. The objective of this study was to evaluate the relationship between
      BODE index and HRQoL in cross-sectional and longitudinal association analyses.
      METHODS: A multi-center prospective cohort study was initially conducted in 491
      stable COPD patients in Beijing, China. Health status (HRQoL) was assessed by St.
      George's Respiratory Questionnaire (SGRQ); the BODE index was calculated for each
      patient; dyspnea was assessed using the 5-grade Medical Research Council dyspnea
      scale. Other measurements included socio-demographic, body mass index (BMI), lung
      function test and 6-minute-walk test (6MWT). Patients were then followed monthly
      for 12 months. RESULTS: Only 450 patients completed the 1-year follow up and were
      enrolled in our present analyses. Mean age was (65.2 +/- 10.6) years, men 309
      (68.7%). The BODE index was categorized into 4 subgroups: 0 - 2, 3 - 4, 5 - 6 and
      7 - 10. At baseline BODE index was gradually increased with baseline total SGRQ
      and SGRQ subscales (P trend < 0.001). For individual components of BODE index,
      with the decrease of airflow limitation, and 6MWD, and with the increase of
      Medical Research Council (MRC) dyspnea grade, total SGRQ and SGRQ subscales were
      increased correspondingly, P trend < 0.05, respectively. Similar association
      patterns were found between baseline BODE index and its individual components and
      mean SGRQ scores at the end of 1-year follow up. By multiple linear regression
      analyses, baseline BODE index was not only significantly associated with SGRQ
      score at baseline but also with SGRQ score at the end of 1-year follow up after
      adjustment for age, male, current smoking, betas being 0.434 and 0.378,
      respectively. CONCLUSIONS: BODE index is associated with SGRQ score cross
      sectionally and longitudinally among stable COPD patients. BODE index might have
      potential to be used as a sensitive tool to assess the status of quality of life
      and to monitor disease progression among stable COPD patients.

PMID- 20137479
TI  - A prospective study comparing endoscopic subcutaneous mastectomy plus immediate
      reconstruction with implants and breast conserving surgery for breast cancer.
AB  - BACKGROUND: Breast conserving surgery (BCS) has been the standard surgical
      procedure for the treatment of early breast cancer. Endoscopic subcutaneous
      mastectomy (ESM) plus immediate reconstruction with implants is an emerging
      procedure. The objective of this prospective study was to evaluate the clinical
      outcomes of these two surgical procedures in our clinical setting. METHODS: From
      March 2004 to October 2007, 43 patients with breast cancer underwent ESM plus
      axillary lymph node dissection and immediate reconstruction with implants, while
      54 patients underwent BCS. The clinical and pathological characteristics,
      surgical safety, and therapeutic effects were compared between the two groups.
      RESULTS: There were no significant differences in the age, clinical stage,
      histopathologic type of tumor, operative blood loss, postoperative drainage time,
      and postoperative complications between the two groups (P > 0.05). The
      postoperative complications were partial necrosis of the nipple and superficial
      skin flap in the ESM patients, and hydrops in the axilla and residual cavity in
      the BCS patients. There was no significant difference in the rate of satisfactory
      postoperative cosmetic outcomes between the ESM (88.4%, 38/43) and BCS (92.6%,
      50/54) patients (P > 0.05). During follow-up of 6 months to 4 years, all patients
      treated with ESM were disease-free, but 3 patients who underwent BCS had
      metastasis or recurrence -one of these patients died of multiple organ
      metastasis. CONCLUSIONS: After considering the wide indications for use, high
      surgical safety, and favorable cosmetic outcomes, we conclude that ESM plus
      axillary lymph node dissection and immediate reconstruction with implants - the
      new surgery of choice for breast cancer - warrants serious consideration as the
      prospective next standard surgical procedure.

PMID- 20137480
TI  - Preliminary results of combined carotid endarterectomy and off-pump coronary
      artery bypass grafting in patients with coexistent carotid and coronary artery
      diseases.
AB  - BACKGROUND: Coexistent carotid and coronary artery diseases are common and
      patients with them remain at a high risk for perioperative stroke or myocardial
      infarction after coronary bypass surgery. The aim of this study was to
      investigate the effect of combined carotid endarterectomy (CEA) and off-pump
      coronary artery bypass grafting (CABG) in patients with coexistent carotid and
      coronary artery diseases. METHODS: Between January 2002 and December 2007,
      consecutive patients with coexistent carotid and coronary artery diseases
      underwent one-stage unilateral CEA and off-pump CABG in Heart Institute of
      Nanjing First Hospital Affiliated to Nanjing Medical University. Perioperative
      complications were assessed and follow-up was carried out. RESULTS: A total of 51
      cases of isolated off-pump CABG and unilateral CEA, including 34 right and 17
      left, were performed. The mean blocked time of carotid artery in CEA was (25.5 +/
      7.0) minutes. The mean number of distal grafts per patient was 3.30 +/- 0.45.
      The mean ventilation time, intensive care unit stay, and postoperative hospital
      stay was (11.3 +/- 5.4) hours, (2.1 +/- 0.9) days, and (12.5 +/- 6.1) days
      respectively. None of the patients had stroke or myocardial infarct. There was
      one perioperative death due to acute cardiac failure, resulting in an operative
      mortality of 1.96%. Follow-up was completed for 47 patients (92.16%) with a mean
      follow-up of (39.5 +/- 12.5) months. None of the patients manifested stroke, new
      angina or newly developed cardiac infarct. No late death occurred. CONCLUSION:
      Combined CEA and off-pump CABG is a safe and effective procedure in selected
      patients with coexistent carotid and coronary artery diseases.

PMID- 20137481
TI  - A follow-up study on features of sensory gating P50 in treatment-resistant
      depression patients.
AB  - BACKGROUND: Depressive disorder is a well-known chronic, recurrent and disabling
      mental disease with high direct and indirect costs to society in both western and
      eastern cultures. Approximately 40% of depressed patients show only partial or no
      response to initial or even multiple antidepressant medications and are usually
      called treatment-resistant depression (TRD) patients. The present work was to
      measure the features of sensory gating (SG) P50 in TRD patients with the intent
      of understanding the characteristics of this disease. METHODS: In 50 TRD
      patients, 39 non-treatment-resistant depression (NTRD) patients and 51 healthy
      controls (HC), auditory evoked potential P50 was measured using the
      conditioning/testing paradigm presented with auditory double clicks stimuli, and
      36 TRD patients had repeated measurements after an 8-week venlafaxine treatment
      course. RESULTS: All the depressive disorder patients, including the TRD and NTRD
      groups, showed an increased testing stimulus wave (S2-P50) amplitude compared to
      controls (P < 0.01 and P < 0.05), but there was no significant difference between
      the TRD and NTRD groups (P > 0.05). There were significant differences in the
      ratio of testing stimulus (S2) and conditioning stimulus (S1) (S2/S1) and in the
      value of 100 x (1 - S2/S1) among the three groups. Compared to the baseline, TRD
      patients had no significant changes of features and different expression of P50
      after acute treatment (P > 0.05). Meanwhile, a statistically significant positive
      correlation of S2/S1 with the scores of the 17-item Hamilton Rating Scale for
      Depression (HAMD-17) (P < 0.01), and a significantly negative correlation of S1 -
      S2, 100 x (1 - S2/S1) with the scores of HAMD-17 (P < 0.01) were observed in the
      TRD patients' baseline measurement, but there was no correlation after
      venlafaxine treatment (P > 0.05). CONCLUSIONS: Both the TRD and NTRD patients had
      obvious SG deficits, with a more severe deficit in TRD patients. Although, with a
      correlated relationship to the severity of depressive symptoms, SG P50 deficit
      might be suggested as a trait marker for TRD, and a combination of S2/S1 ratio,
      S1 - S2 and 100 x (1 - S2/S1), was recommended for electrophysiological
      measurement in TRD patients.

PMID- 20137482
TI  - Development of sympathetic ophthalmia following globe injury.
AB  - BACKGROUND: Sympathetic ophthalmia (SO), a rare, bilateral, diffuse granulomatous
      uveitis, usually occurs after open globe injury or intraocular surgery. We sought
      to identify the risk factors for the development of SO after open globe injury
      and describe their demographic and clinical features and outcomes of treatments.
      METHODS: A retrospective study of inpatients with globe injury in 15 tertiary
      referral hospitals of China from January 2001 to December 2005 was conducted. The
      information of demography, nature and mechanism of injury, time and ways of
      treatments and outcomes was reviewed. Diagnosis of SO was made based on a history
      of ocular trauma or surgery and subsequent development of bilateral or
      contralateral uveitis consistent with SO. Any association between related
      parameters and development of SO was analyzed. RESULTS: Among 9103 patients (9776
      eyes) of globe injury, SO occurred after open globe injury in 18 cases with an
      occurrence rate of 0.37%, vitrectomy of closed globe injury in 2 (0.37%) and
      perforation of burned eyes in another 2. For open globe injury, the median age
      ((36.72 +/- 13.59) years, P = 0.01) was higher in patients with SO; there were no
      significant effects of sexes, injury type, uvea proplaps, once or multi
      intraocular surgery, once or multi-vitrectomy and endophthalmitis on incidence of
      SO; 0.70% endophthalmitis concurred with SO; 83.33% of SO occurred within 1 year
      after injury or last ocular surgery. SO developed in a fellow eye one week after
      evisceration of the perforating burned eye. Good final visual acuity was obtained
      in sympathizing eyes with prompt treatment. CONCLUSIONS: For open globe injuries,
      SO sufferers were relatively older and any injury type could induce SO with equal
      possibility. The initial open globe injury was more likely to be the trigger of
      SO than subsequent intraocular surgeries including vitrectomy. Prophylactic
      enucleation after injury is not recommended.

PMID- 20137483
TI  - Application of endoscopic retrograde cholangiopancreatography in biliary
      pancreatic diseases.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been used
      increasingly for the treatment of choledocholithiasis, gallstone pancreatitis,
      and benign or malignant bile duct or pancreatic duct stenosis. The purpose of
      this study was to evaluate ERCP for the diagnosis and therapy of biliary
      pancreatic diseases. METHODS: A total of 2075 patients who underwent diagnostic
      and therapeutic ERCP from June 2001 to March 2009 were analyzed retrospectively.
      Achievement and complication rates were calculated, and the therapeutic effect
      was observed. RESULTS: In all the 64 cases who underwent diagnostic ERCP, the
      procedure was successful, in 2011 cases therapeutic ERCP was performed, and the
      success rate was 94.6%. In the therapeutic ERCP cases, 1434 (93.0%) were
      successful among the 1542 cases of choledocholithiasis, and 422 (90.0%) of the
      469 cases with benign or malignant bile duct or pancreatic duct stenosis, or
      acute obstructive suppurative cholangitis with stent placement or endoscopic
      nasobiliary drainage were successful. Fifty-nine (90.8%) cases of the 65 who
      underwent a pre-cut for pancreatic sphincterotomy were successful. Complication
      rate was 5.1% and the most frequent complication was acute pancreatitis (4.4%).
      CONCLUSIONS: ERCP is one of the major diagnostic and therapeutic methods for
      biliary-pancreatic disease. Therapeutic ERCP is a minimally invasive, safe and
      effective treatment method for various biliary-pancreatic diseases.

PMID- 20137484
TI  - Clinical study of simultaneous lung volume reduction surgery during resection of
      pulmonary or esophageal neoplasms.
AB  - BACKGROUND: If the emphysema lesions are not symmetrical, unilateral lung volume
      reduction surgery (LVRS) can be carried out on the more severe side. The aim of
      this research was to evaluate the feasibility and effects of LVRS performed
      simultaneously with resection of pulmonary and esophageal neoplasms. METHODS:
      Forty-five patients with pulmonary neoplasm and 37 patients with esophageal
      neoplasm were randomly assigned to group A or group B. In group A, LVRS was
      performed simultaneously on the same side as thoracotomy. In group B, only tumor
      resection was performed. The nonfunctional lung area was determined by
      preoperative chest computed tomography and lung ventilation/perfusion scan. The
      lung volume removed was about 20% to 30% of the lobes on one side. Preoperative
      and postoperative indexes including pulmonary function testing variables,
      arterial blood gas analysis variables, dyspnea scale, 6-minute walk distance,
      etc., were compared between the groups. RESULTS: There were no surgical deaths in
      this study. The postoperative forced vital capacity in 1 second, PaO2, PaCO2,
      dyspnea scale, and 6-minute walk distance were improved significantly in group A,
      whereas these indexes did not change or decreased slightly in group B.
      CONCLUSIONS: For tumor patients who have associated emphysema, simultaneous LVRS
      not only increases the chance of receiving surgical therapy, but also improves
      the postoperative quality of life of the patient. LVRS has expanded the surgical
      indication for tumor patients.

PMID- 20137485
TI  - Influence of peritoneal transfer status on fasting blood glucose in non-diabetic
      nephropathy patients on continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: Extra glucose load in peritoneal dialysis is an important cause of
      newly-occurred diabetic mellitus, which initiates insulin treatment in some of
      the dialytic patients. The purpose of this study was to discuss the influence of
      the peritoneal transfer status on fasting blood glucose in non-diabetic
      nephropathy patients who are on continuous ambulatory peritoneal dialysis (CAPD).
      METHODS: One hundred and forty-five patients with total KT/V per week over 2.0
      were recruited, including 60 males and 85 females. Fasting blood glucose (FBG),
      creatinine, blood urea nitrogen (BUN), blood albumin, blood lipid profile and
      blood C-reactive protein (CRP) were analyzed at the beginning of the peritoneal
      dialysis and after 12 months. A peritoneal equilibration test (PET) was carried
      out at the 3rd month of CAPD, and meantime residual renal function, peritoneal
      solute clearance rate, ultrafiltration volume and urine volume were also
      evaluated. RESULTS: Twenty-one cases were identified as a low transfer group (L),
      32 cases as a low average transfer group (LA), 58 cases as a high average
      transfer group (HA) and 34 cases as a high transfer group (H). At the end of the
      12th month, 83 cases had elevated FBG. Through stepwise multiple regression
      analysis we found the FBG level in these patients was positively related to
      glucose load and CRP, and negatively related to glucose absorption in the
      peritoneum (D/D(0)) and blood albumin (P < 0.05). Kaplan-Meier analysis during a
      48-month follow-up found the morbidity of hyperglycemia to be 17/34 cases (50.1%)
      in the high transfer group, 20/58 cases (34.5%) in the high average transfer
      group, 11/32 cases (34.3%) in the low average transfer group, and 1/21 cases
      (5.4%) in the low transfer group. CONCLUSIONS: Patients with high peritoneal
      transfer capacity might have the highest morbidity from hyperglycemia among
      patients with these four different peritoneal transfer status. Glucose load,
      baseline CRP and FBG level before peritoneal dialysis, and D/D0 can efficiently
      predict hyperglycemia in CAPD patients.

PMID- 20137486
TI  - Value of left ventricular regional ejection fraction determined by real-time
      three-dimensional echocardiography in diagnosis of aneurysm: compared with left
      ventriculography.
AB  - BACKGROUND: Regional ejection fraction (EF(R)) measured by real-time three
      dimensional echocardiography (RT-3DE) provides a novel method for quantifying
      left-ventricular (LV) regional systolic function. We aimed to explore the
      diagnostic value of regional ejection fraction (EFR) derived from RT-3DE in
      detecting LV aneurysms in patients with myocardial infarction. METHODS: Thirty
      eight patients with myocardial infarction were prospectively enrolled and
      underwent electrocardiography (ECG), two-dimensional echocardiography (2-DE), RT
      3DE and left ventriculography (LVG). Subjects with a negative EFR in at least one
      segment on RT-3DE were considered as having a ventricular aneurysm. We compared
      the sensitivity, specificity, Youden's index, and positive and negative
      predictive values of ECG, 2-DE and RT-3DE in determining LV aneurysm with
      detection by LVG. RESULTS: On LVG an LV aneurysm was diagnosed in 16 (42.1%)
      patients. The sensitivity and specificity were 62.5% and 86.4% for ECG, 81.2% and
      95.4% for 2-DE, and 100.0% and 90.9% for RT-3DE in diagnosing LV aneurysm.
      Youden's indexes for ECG, 2-DE and RT-3DE were 0.49, 0.77 and 0.91, respectively.
      Positive and negative predictive values were 76.9% and 76.0% for ECG, 92.9% and
      87.5% for 2-DE, and 88.9% and 100.0% for RT-3DE. CONCLUSIONS: RT-3DE-derived EFR
      provides a novel, reliable index in the diagnosis of LV aneurysm and has
      excellent sensitivity and specificity.

PMID- 20137487
TI  - Arterioles in cerebral amyloid angiopathy and vascular dementia.
AB  - BACKGROUND: Small cerebrovascular lesions are one of the most important factors
      in cerebral amyloid angiopathy (CAA) and vascular dementia (VaD). We analyzed the
      difference of arteriolar pathology between CAA patients (CAAs) and vascular
      dementia patients without CAA (VaDs). METHODS: Ten deceased CAAs and twelve
      deceased VaDs were available for this study. Five deceased patients without known
      cerebrovascular diseases served as controls. These patients were all autopsy
      cases. All transversely cut arterioles in the gray matter and white matter with
      an external diameter equal to or larger than 30 microm and with a maximum of 300
      microm were examined. The internal and external diameters of arterioles were
      measured. RESULTS: The external diameter of gray matter arterioles in the CAAs
      was significantly greater than in controls. In gray matter arterioles, the
      diameter of the lumen in VaDs was markedly smaller than in the CAAs, whereas
      there was no significant difference between CAAs and controls. CAAs and VaDs may
      cause remarkable thickening of the arteriolar walls in either white matter or
      gray matter. The sclerotic index of arterioles in VaDs was significantly greater
      than in CAAs and controls. CONCLUSIONS: Stenosis of arterioles occurred in both
      CAA and VaD, but the tendency was greater in VaD. Arterioles of CAA were also
      expanded in gray matter, which may be related to lobar hemorrhage. The loss
      and/or degeneration of vascular smooth muscle cells was predominant in CAA, while
      the over-proliferation of vascular smooth muscle cells was greater in VaD.

PMID- 20137488
TI  - Association between DPP6 polymorphism and the risk of sporadic amyotrophic
      lateral sclerosis in Chinese patients.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative
      disease characterized by the loss of motor neurons in the spinal cord, brainstem,
      and cerebral cortex, which results in muscle weakness, atrophy. Sporadic ALS
      (SALS) accounts for about 90% of ALS cases, but the etiology is largely unknown.
      Most of the researchers consider it to be a complex disease. There have been
      several genome-wide association (GWA) studies reporting several single nucleotide
      polymorphisms (SNPs) which are susceptible to ALS, but no data of Asians
      (including Chinese) yet. We investigate whether the polymorphism of rs10260404 in
      DPP6 gene is associated with SALS in Chinese Han origin to compare the ethnic
      differences between Chinese Han origin and other populations. METHODS: The
      genomic DNA was extracted from the leukocytes of whole blood samples in 58
      Chinese Han patients with SALS and 52 healthy controls. The asymmetric PCR was
      processed in the presence of an unlabeled probe that contained the rs10260404
      locus. The product was genotyped on a light scanner using high resolution melting
      method and some were confirmed with sequencing. RESULTS: The rs10260404
      polymorphism was in Hardy-Weinberg equilibrium in patients and controls. The CC
      genotype and the C allele were similar in patients compared with healthy subjects
      and not associated with an increased risk of Chinese SALS patients (chi(2) =
      0.29, OR = 1.26, 95% CI 0.55 - 2.87, P > 0.05). CONCLUSIONS: The rs10260404 is
      not associated with ALS susceptibility in Chinese people with Han origin which
      may be due to ethnic differences. More study with large number of cases in
      Chinese population is really necessary.

PMID- 20137489
TI  - Neoadjuvant chemotherapy in patients with stages II and III breast cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy has been used as a primary treatment for
      locally advanced or inflammatory breast cancer, and recently extended to operable
      breast cancer. However, only a few studies have published data concerning the
      outcomes of patients with stages II and III breast cancer after neoadjuvant
      chemotherapy. METHODS: This study retrospectively investigated the clinical value
      of neoadjuvant chemotherapy for patients with stages II and III breast cancer.
      The patients in Group 1 (n = 54) were treated with neoadjuvant chemotherapy,
      followed by definitive surgery and adjuvant therapy. The patients in Group 2 (n =
      43) initially received definitive surgery, followed by adjuvant chemotherapy and
      other therapies. The operability rates for breast conservation and dermatoplasty
      were observed in Group 1 after neoadjuvant chemotherapy. After follow-up, the
      recurrence and overall and disease-free survival rates of the two groups were
      analyzed. RESULTS: Neoadjuvant chemotherapy increased the operability rates for
      breast conservation from 17.1% to 40.0% in stage II (P = 0.034) and 0% to 12.6%
      in stage III (P = 0.016), and decreased the dermatoplasty rates from 17.1% to
      2.8% in stage II (P = 0.046) and 28.1% to 8.1% in stage III (P = 0.026). After a
      median follow-up of 46.8 months, there were 11 deaths and 13 recurrences in Group
      1, and 15 deaths and 19 recurrences in Group 2. The overall and disease-free
      survival rates of stage III disease were significantly higher in Group 1 than in
      Group 2 (68.4% vs 31.2%, P = 0.028, and 63.2% vs 25.0%, P = 0.024, respectively).
      There were no significant differences in the overall and disease-free survival
      rates of stage II disease for Group 1 compared with Group 2 (85.7% vs 85.2%, P =
      0.953, and 80.6% vs 74.1%, P = 0.400, respectively). CONCLUSIONS: Neoadjuvant
      chemotherapy resulted in increased operability for breast conservation and
      decreased dermatoplasty. Neoadjuvant chemotherapy exhibited better recurrence
      control, and overall and disease-free survival rates in stage III disease.
      However, neoadjuvant chemotherapy did not confer greater survival on stage II
      disease.

PMID- 20137490
TI  - Magnetic resonance imaging of the extraocular muscles and corresponding cranial
      nerves in patients with special forms of strabismus.
AB  - BACKGROUND: With the technical advances, magnetic resonance imaging (MRI) is now
      sensitive enough to detect subtle structural abnormalities of ocular motor nerves
      arising from the brainstem and orbits of living subjects. This study was designed
      to delineate the MRI characteristics in patients with special forms of
      strabismus. METHODS: A total of 29 patients with special forms of strabismus
      underwent orbital and intracalvarium MRI. Imaging of the ocular motor nerves in
      the brainstem was performed in 0.8 mm thickness image planes using the three
      dimensional fast imaging employing steady-state acquisition (3D-FIESTA) sequence.
      Nerves to extraocular muscles (EOMs), EOMs and their associated connective
      tissues were imaged with T1 weighting in tri-planar scans by dual-phased coils
      within 2.0 mm thick planes. RESULTS: Patients with congenital fibrosis of the
      extraocular muscles exhibited hypoplasia of the oculomotor (CN3), abducens (CN6),
      trochlear (CN4) nerves, and the EOMs; hypoplasia of CN6 in the brainstem and an
      extra branch of the inferior division of CN3 to the lateral rectus were the most
      common but not the only presentation of Duane's retraction syndrome. Hypoplasia
      of CN6, facial (CN7) and hypoglossal (CN12) nerves were revealed in patients with
      Mobius syndrome. In a rare case of bilateral synergistic convergence and
      divergence, an enlarged branch of CN3 to the medial rectus and a questionable
      branch of CN3 to the inferior rectus bilaterally were found. CONCLUSION: MRI can
      reveal subtle structures of the ocular motor nerves and their corresponding EOMs.
      This can provide valuable information regarding pathogenesis in some special
      forms of strabismus.

PMID- 20137491
TI  - Comparison of emergency endoscopic variceal ligation plus octride or octride
      alone for acute esophageal variceal bleeding.
AB  - BACKGROUND: Octride was the main method for the treatment of esophageal variceal
      bleeding (EVB). The aim of this study was to compare the cost-effect and safety
      between esophageal variceal ligation (EVL) plus octride and octride alone in
      acute esophageal bleeding. METHODS: A total of 101 cirrhotic patients with EVB
      were involved in this study and received emergency EVL + octride (EVL group) or
      only octride therapy randomly. The cost, efficacy and safety were analyzed and
      compared between the two groups. RESULTS: Among 51 patients in EVL group, 5 (10%)
      patients failed. Among 50 patients in the octride treatment group, 13 patients
      (26%) failed. The difference was significant (P < 0.05). The average blood
      transfusion volume was (2.4 +/- 2.2) units in the EVL group and (6.4 +/- 3.4)
      units in the octride treatment group (P < 0.05). Hospital stay was (7.4 +/- 1.3)
      days in the EVL group and (11.4 +/- 3.3) days in the octride treatment group (P <
      0.05). The average hospital cost was (10 983 +/- 1147) yuan in the EVL group and
      (13 921 +/- 2107) yuan in the octride treatment group (P < 0.05). CONCLUSION:
      Emergency endoscopic ligation plus octride is superior to octride alone in the
      treatment of acute EVB with lower cost and higher efficacy with enough safety.

PMID- 20137492
TI  - Clinical follow-up of ceramic bridges with auro-galvanoforming primary coping and
      Ni-Cr pontic for restoration of dentition defects.
AB  - BACKGROUND: Alternatives to the conventional auro-galvanoforming ceramic bridge
      need to be evaluated in long-term longitudinal studies before being recommended
      for restoration of dentition defects. This study aimed to evaluate the clinical
      performance of a ceramic bridge with auro-galvanoforming primary coping and Ni-Cr
      pontic for restoration of dentition defects. METHODS: In total, 114 ceramic
      bridges with auro-galvanoforming (primary coping and Ni-Cr pontic) were placed in
      112 patients with dentition defects. Among them, 83 bridges in 82 patients were
      available for follow-up after 7 years. We evaluated marginal integrity, color
      match, gingival inflammation, fracture of ceramic bridges, and recurrent caries.
      RESULTS: Marginal integrity of the ceramic bridges was perfect in all patients.
      Most ceramic bridges maintained their original color. Fracture was found in three
      bridges; the rest were free of fracture, breakage, and loosening. Recurrent
      abutment caries were not found. Ceramic bridges with auro-galvanoforming (primary
      coping and Ni-Cr pontic) produced satisfactory clinical outcomes - equivalent to
      the conventional porcelain-fused-to-metal restoration. This technique is
      especially useful for dentition defects of the molar area and is cheaper than
      restoration with noble metal bridges. CONCLUSIONS: Ceramic bridges with auro
      galvanoforming (primary coping and Ni-Cr pontic) performed well for the
      restoration of dentition defects during this follow-up period. More studies are
      warranted to further evaluate this technique as an alternative to the
      conventional porcelain-fused-to-metal restoration.

PMID- 20137493
TI  - Cell-wall-deficient bacteria: a major etiological factor for psoriasis?
AB  - BACKGROUND: Psoriasis is a common inflammatory skin disease, yet knowledge of the
      factors that may induce, trigger, or exacerbate psoriasis is not fully
      delineated. Recent advances have improved our understanding of the link between
      psoriasis and cell-wall-deficient bacteria (CWDB) infections. In the present
      study we assessed the prevalence of CWDB infection in patients with psoriasis.
      METHODS: The carriage rate of CWDB in the tonsil or pharynx of psoriasis
      patients, chronic tonsillitis patients and controls were investigated using
      hypertonic medium. Psoriasis patients with CWDB were randomly assigned to two
      groups and respectively treated with antibiotics or systemic therapy without
      antibiotic. Human peripheral blood mononuclear cells (PBMC) from psoriasis
      patients, chronic tonsillitis patients and control subjects were stimulated with
      bacteria antigens and extra-cellular levels of interferon-gamma (IFN-gamma) and
      interleukin (IL)-10 were measured in the supernatants using the ELISA technique,
      in vitro. Meanwhile, the proliferation ability of PBMC to respond to bacteria
      antigens was detected by MTT assay. RESULTS: CWDB were isolated from 74.2% of
      psoriasis patients, 23.5% of chronic tonsillitis patients and only 6.3% of
      controls. Antibiotic therapy was appropriate for approximately 80% of psoriasis
      patients with CWDB infection, and in only 8.9% psoriasis patients CWDB infection
      was detected after antibiotic therapy. Meanwhile, our study showed that CWDB and
      wide-type bacteria did remarkably enhance the production of IFN-gamma, in vitro,
      and PBMC proliferation. CONCLUSION: CWDB infection may be a virtual triggering
      factor in psoriasis by regulating T-cell activation.

PMID- 20137494
TI  - Dorsal penile nerves and primary premature ejaculation.
AB  - BACKGROUND: Based on our clinical experience, the number of dorsal penile nerves
      in patients with primary premature ejaculation (PPE) is not consistent with the
      average number (2 branches). In this study, we evaluated the number and
      distribution of dorsal penile nerves among healthy Chinese adults and patients
      with PPE. METHODS: The dorsal nerve of the penis, the deep dorsal vein of the
      penis, and the dorsal artery of the penis between the deep fascia of the penis
      and the albuginea penis were carefully educed, observed, and counted in 38 adult
      autopsy specimens. The number and distribution of the dorsal penile nerve in 128
      surgical patients with PPE were determined. RESULTS: The numbers of dorsal penile
      nerves of the 38 cases were as follows: 7 branches in 1 case; 6 branches in 1
      case; 5 branches in 6 cases; 4 branches in 9 cases; 3 branches in 14 cases; and 2
      branches in 7 cases. Most of the dorsal nerves were parallel to each other and in
      the dorsum of the penis. In only 8 cases, the branches were connected by some
      communicating branches. In 4 cases, 1 or 2 thin dorsal nerves continued their
      pathway over the ventral aspect of the penis. The average number of branches of
      the dorsal penile nerve in patients with PPE was 7.16. CONCLUSIONS: Based on the
      study of 38 cases, the average number of dorsal penile nerves was 3.55 branches
      and that of patients with PPE was greater. These preliminary results suggest that
      the excessive dorsal penile nerves may have an impact on PPE via increased
      sensitivity and provide topographic data for the possible treatment of PPE.

PMID- 20137495
TI  - Effects of antiallergic herbal agents on cystic fibrosis transmembrane
      conductance regulator in nasal mucosal epithelia of allergic rhinitis rabbits.
AB  - BACKGROUND: It has been found that the expression of cystic fibrosis
      transmembrane conductance regulator (CFTR) is closely related to allergic
      rhinitis (AR). In the previous study, we have demonstrated that antiallergic
      herbal agents (AHA) can obviously inhibit the allergic reaction of AR. The aim of
      this study was to explore the expression of CFTR and the effects of AHA on CFTR
      to improve the allergic reaction of AR. METHODS: An animal model of an AR rabbit
      was established using ovalbumin (OVA). The rhinitis rabbits were randomly
      assigned to three groups: AHA treating group (AHATG), modeling group (MG) and
      healthy controlling group (HCG). The expressions of CFTR protein were examined by
      immunohistochemical method. The mucosal epithelial cells of all the rabbits were
      primarily cultured with tissue culture method in vitro and treated with or
      without glibenclamide for 24 hours. The levels of monocyte chemotactic factor-1
      (MCP-1) and RANTES protein in supernatants of culture were measured by ELISA, and
      the expressions of CFTR mRNA were detected by real-time PCR. RESULTS: The
      expressions of CFTR mRNA and protein greatly increased in mucosal epithelial
      cells of MG. The protein concentrations of MCP-1, RANTES in culture supernatants
      of MG were significantly higher than those in the other two groups (P < 0.01),
      and they reached much higher level than those at the start points in the MG (P <
      0.05) and were significantly different compared with those in the AHATG after
      being cultured for 24 hours (P < 0.01). CFTR mRNA in MG + glibenclamide were much
      lower than those in MG (P < 0.05). RANTES and CFTR mRNA treated with
      glibenclamide in AHATG were significantly lower than those in the AHATG (P <
      0.01). Minimal changes in the secretions of MCP-1 in the epithelial cells were
      detected between AHATG and AHATG + glibenclamide (P > 0.05). CONCLUSIONS: AHA can
      inhibit the secretions of CFTR, RANTES and MCP-1 in mucosal epithelia and improve
      inflammatory reaction of AR. CFTR may play an important role in the secretion of
      RANTES and mucosal inflammatory response in AR. Glibenclamide can inhibit the
      CFTR secretion in mucosal epithelial cells, in particular during AR process.
      These effects of glibenclamide on secretion of RANTES can be effectively
      strengthened by AHA.

PMID- 20137496
TI  - Changes of sphingolipids profiles after ischemia-reperfusion injury in the rat
      liver.
AB  - BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury occurs in many clinical
      procedures. The molecular mechanisms responsible for hepatic I/R injury however
      remain unknown. Sphingolipids, in particular ceramide, play a role in stress and
      death receptor-induced hepatocellular death, contributing to the progression of
      several liver diseases including liver I/R injury. In order to further define the
      role of sphingolipids in hepatic I/R, systemic analysis of sphingolipids after
      reperfusion is necessary. METHODS: We investigated the lipidomic changes of
      sphingolipids in a rat model of warm hepatic I/R injury, by delayed extraction
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE
      MALDI-TOF-MS). RESULTS: The total amounts of ceramide and sphingomyelin and the
      intensity of most kinds of sphingolipids, mainly sphingomyelin, significantly
      increased at 1 hour after reperfusion (P < 0.05) and reached peaks at 6 hours
      after reperfusion (P < 0.01) compared to controls. Six new forms of ceramide and
      sphingomyelins appeared 6 hours after reperfusion, they were (m/z) 537.8, 555.7,
      567.7, 583.8, 683.5 and 731.4 respectively. A ceramide-monohexoside (m/z) 804.4
      (CMH(d18:1C22:1+Na)(+)) also increased after reperfusion and correlated with
      extent of liver injury after reperfursion. CONCLUSIONS: Three main forms of
      sphingolipids, ceramide, sphingomyelin and ceramide-monohexoside, are related to
      hepatic I/R injury and provide a new perspective in understanding the mechanisms
      responsible for hepatic I/R injury.

PMID- 20137497
TI  - Hydrogen sulfide induces apoptosis of pulmonary artery smooth muscle cell in rats
      with pulmonary hypertension induced by high pulmonary blood flow.
AB  - BACKGROUND: Abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs)
      is an important pathophysiological process in the pulmonary artery structural
      remodeling and pulmonary hypertension. We investigated possible effect of
      endogenous hydrogen sulfide (H2S) on apoptosis of PASMCs during the development
      of pulmonary hypertension induced by high pulmonary blood flow. METHODS: Thirty
      nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week
      shunt, 4-week shunt + propargylglycine (PPG), 11-week control, 11-week shunt and
      11-week shunt + sodium hydrosulfide (NaHS) groups. Rats in 4-week shunt, 4-week
      shunt + PPG, 11-week shunt and 11-week shunt + NaHS groups underwent an abdominal
      aorta-inferior vena cava shunt. Rats in 4-week shunt + PPG group were
      intraperitoneally injected with PPG, an inhibitor of endogenous H2S production,
      for 4 weeks. Rats in 11-week shunt + NaHS group were intraperitoneally injected
      with NaHS, a H2S donor, for 11 weeks. Lung tissue H2S was evaluated by sulfide
      sensitive electrode. Apoptosis of PASMCs were detected by terminal
      deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL).
      Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with
      immunochemical staining. RESULTS: Four weeks after the shunting operation, the
      apoptosis of PASMCs and expression of Fas and caspase-3 were significantly
      decreased (P < 0.01), but expression of bcl-2 increased significantly (P < 0.01).
      PPG administration further inhibited the apoptosis of PASMCs, downregulated the
      expression of Fas and caspase-3 (P < 0.01), but increased the expression of bcl-2
      (P < 0.01). After 11 weeks of shunting operation, the apoptosis of PASMCs and
      expression of Fas and caspase-3 were significantly decreased (P < 0.01), but
      expression of bcl-2 increased obviously (P < 0.01). NaHS administration
      significantly increased the apoptosis of PASMCs, upregulated the expression of
      Fas and caspase-3, but inhibited the expression of bcl-2. CONCLUSIONS: H2S
      induces the apoptosis of PASMCs in the development of high pulmonary blood flow
      induced pulmonary hypertension by activating the Fas pathway and inhibiting the
      bcl-2 pathway.

PMID- 20137498
TI  - Effects of cryptotanshinone on immune functions in rats with adjuvant arthritis.
AB  - BACKGROUND: Cryptotanshinone (CT) was originally isolated from the dried roots of
      Salvia militorrhiza, an herb that is used extensively in Asian medicine and the
      extracts of this herb have been used in the treatment of several pathologies,
      including cardiovascular diseases, hematological abnormalities, hepatitis, and
      hyperlipidemia, but no studies had been carried on the treatment for rheumatic
      diseases with it. This study aimed to investigate the effects of cryptotanshinone
      on immune functions in rats with adjuvant arthritis (AA). METHODS: Complete
      Freund's adjuvant was used to induce AA in rats. Thymus and spleen was
      aseptically taken from normal rats and the AA rats. Then a thymus lymphoid cell
      suspension, splenic lymphoid cell suspension and peritoneal macrophage cell
      suspension were prepared. After adding CT (0.1 microg/ml, 1.0 microg/ml, 10
      microg/ml, 100 microg/ml, 1000 microg/ml) into the suspension, T and B
      lymphocytes proliferation was determined by 3-(4,5-2 dimethylthiazal-2yl)2,5
      diphenyltetrazoliumbromide (MTT) assay. And the activities of interleukin-1 (IL
      1) and IL-2 were measured by the mouse lymphocytes proliferation assay. RESULTS:
      Thymic T and splenic B lymphocyte proliferation of the AA rat was significantly
      lower, and could be stored through using CT in vitro. CT (100 microg/ml and 1000
      microg/ml) increased T or B lymphocytes proliferation in vitro (P < 0.01). In AA
      rats, the levels of IL-1 released by abdominal PMPhi significantly increased
      whereas the level of IL-2 released by T cells decreased in vitro. CT (1000
      microg/ml) decreased the production of IL-1 and promoted production of IL-2 in
      vitro (P < 0.05). CONCLUSIONS: CT can ameliorate the abnormal immunological
      functions in AA rats.

PMID- 20137499
TI  - Changes of splenic macrophage during the process of liver cancer induced by
      diethylnitrosamine in rats.
AB  - BACKGROUND: It is generally accepted that spleen plays a complex role in the
      tumor immunity, which would change in the different periods of cancer. In this
      study, we investigated the changes in the function of splenic macrophage (Mphi)
      in different stages of liver cancer induced by diethylnitrosamine (DEN) in rats.
      The aim was to support the characteristics of "two-way" and "phase" of spleen in
      tumor immunity. METHODS: The model of pulmonary metastasis of liver cancer was
      established in forty male SD rats by DEN. In the 8th, 13th and 16th week, 10 rats
      were randomly chosen and sacrificed, and divided into cirrhosis, liver cancer and
      pulmonary metastasis groups depending on the pathological result, respectively.
      The other 10 rats were taken as control group. The Mphi was isolated by anchoring
      cultivation. The changes in ultrastructure, phagocytosis, cytokine secretion,
      antigen processing and presenting, and viability of splenic Mphi were detected by
      transmission electron microscopy, Vybrant(TM) Phagocytosis Assay, DQ(TM)
      Ovalbumin, and rat TNF-alpha ELISpot kits. RESULTS: Under the electron
      microscope, the Mphi in the control group had some pseudopodium-like prominences,
      and mitochondria, ribosome, rough endoplasmic reticulum, lysosome can be found in
      the cytoplasm, and phagocytized RBC. In the liver cirrhosis and liver cancer
      group, Mphi had more prominences, meanwhile much more mitochondria, ribosome,
      rough endoplasmic reticulum, lysosome can be found in the cytoplasm, especially
      in the liver cancer group. In the pulmonary metastasis group, the Mphi was
      swelling, with few organelle. As compared to the control group, the function of
      splenic Mphi increased in cirrhosis and cancer groups, but decreased in
      metastasis group (phagocytosis rate: (84.7 +/- 1.9)%, (89.5 +/- 3.1)%, and (36.0
      +/- 2.6)% vs (75.6 +/- 1.7)%, P < 0.05, P < 0.01; viability: (1.53 +/- 0.15)%,
      (1. +/- 0.14)%, and (1.12 +/- 0.29)% vs (1.48 +/- 0.17)%, P < 0.05, P < 0.01; TNF
      alpha secretion: (741.0 +/- 52.9)%, (1126.2 +/- 174.5)%, and (313.8 +/- 50.8)% vs
      (626.6 +/- 24.6)%, P < 0.05, P < 0.01; positive cell rate of antigen processing
      and presenting: (24.03 +/- 1.87)%, (27.95 +/- 2.63)%, and (10.46 +/- 2.16)% vs
      (16.45 +/- 1.86)%, P < 0.01). CONCLUSIONS: In the stage of cirrhosis and early
      cancer, the immune functions of splenic Mphi were reinforced. It may promote the
      non-specificity tumor immunity. On opposite, in the stage of pulmonary
      metastasis, the immune functions of splenic Mphi were impaired. It may lead to
      the decrease of tumor immunity.

PMID- 20137500
TI  - Propofol improves cardiac functional recovery after ischemia-reperfusion by
      upregulating nitric oxide synthase activity in the isolated rat hearts.
AB  - BACKGROUND: There are few studies to assess whether propofol attenuates
      myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide
      (NO) route, so we designed this randomized blinded experiment to observe the
      changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the
      myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and
      to assess the relation between myocardial NO system and cardioprotection of
      propofol. METHODS: The hearts of 30 Sprague-Dawley male rats were removed,
      mounted on a Langendorff apparatus, and randomly assigned to one of three groups
      (n = 10 each group) to be treated with the following treatments in a blinded
      manner: Group 1, control group, after perfusion with pure Krebs Henseleit
      bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20
      minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB
      buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol
      (10 microg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia
      followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3,
      after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) and
      L-NAME (100 micromol/L) for 15 minutes, the hearts underwent 20 minutes global
      ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution.
      The cardiac function was continuously monitored throughout the experiment. The
      coronary flow was also measured. An ISO-NO electrode was placed into the right
      atrium close to the coronary sinus to continuously measure NO concentration in
      the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2
      were obtained to measure the NOS activity by spectrophotometry and the NOS
      contents by immunohistochemistry, respectively. RESULTS: The cardiac function was
      significantly inhibited after ischemia and then gradually improved with
      reperfusion in all three groups. As compared with Group 1, the cardiac function
      variables and coronary flow at all the observed points were significantly
      improved in Group 2. The cardiac function variables and coronary flow were better
      in Group 3 than in Group 1, but were inferior in Group 3 than in Group 2. Both NO
      contents and NOS activity in the myocardium were significantly higher in Group 2
      than in Group 1. However, NOS contents in the myocardium did not significantly
      differ between Groups 1 and 2. CONCLUSIONS: In isolated rat hearts, propofol can
      improve cardiac functional recovery after ischemia-reperfusion by upregulating
      NOS activity in the myocardium. The NO system may play an important role in the
      preservation of myocardial ischemia-reperfusion injury produced by propofol.

PMID- 20137501
TI  - Effect of aspirin on high glucose-induced senescence of endothelial cells.
AB  - BACKGROUND: Endothelial cell senescence is accelerated under high glucose
      condition, which may contribute to the vascular complications in the diabetics.
      It has been proved that aspirin has multiple cytoprotective effects. This study
      aimed to investigate the effect of aspirin on high glucose-induced endothelial
      cell senescence and its possible mechanism. METHODS: Human umbilical venous
      endothelial cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with
      different treatments including the normal glucose (5.5 mmol/L), high glucose (33
      mmol/L) and aspirin (0.01 - 1.00 mmol/L) with high glucose. And 300 micromol/L L
      NAME was added to the culture medium when needed. After 48 hours, SA-beta-gal
      staining was used to evaluate the senescence. Total nitric oxide (NO) production
      and NO synthase (NOS) activity were measured using Griess reaction and molecular
      probes of 3-amino-4-aminomethyl-2', 7'-difluorescein, diacetate. The level of
      intracellular reactive oxygen species was monitored by flow cytometry using 2',
      7'-dichlorofluorescein diacetate. Endothelial NOS (eNOS), caveolin-1 protein
      expressions and caveolin-1/eNOS interaction were analyzed by immunoblotting and
      immunoprecipitation respectively. Asymmetric dimethylarginine (ADMA)
      concentration was determined by high-performance liquid chromatography. RESULTS:
      Exposure to 33 mmol/L glucose for 48 hours significantly increased the number of
      SA-beta-gal positive cells. Co-incubation with aspirin markedly inhibited SA-beta
      gal activity dose-dependently. Aspirin increased NOS activity with eNOS protein
      expression unchanged and increased NO levels and alleviated oxidative stress.
      Consistent with these findings, caveolin-1 expression, caveolin-1/eNOS
      interaction and ADMA accumulation were also decreased. All the inhibitory effects
      of aspirin on senescence were completely obliterated by L-NAME, the NOS
      inhibitor. CONCLUSION: The anti-senescent effects of aspirin are fulfilled by
      increasing NO production via the up-regulation of NOS activity and preventing
      caveolin-1 expression, caveolin-1/eNOS interaction and ADMA accumulation.

PMID- 20137502
TI  - Imaging of low back pain: comparative role of high intensity zone in diagnosing
      the discogenic low back pain with evidence-based radiology.
AB  - BACKGROUND: Discography is a gold standard for the diagnosis of the low back pain
      (LBP), but it has potential dangers for the development of discitis, cerebral
      spinal fluid leakage, retroperitoneal bleeding, acute new back pain and the
      tremendous radiation exposure to the patient. Using "evidence-based radiology"
      methods, the comparative roles of high intensity zone (HIZ) in diagnosing
      discogenic LBP were evaluated. METHODS: A focused clinical question was designed
      and a Pubmed and manual search were performed to identify the role of HIZ on MRI
      T2WI compared with discography. The studies retrieved were assessed for validity
      and strength. Sensitivity, specificity, likelihood ratios (LRs) and graphs of
      conditional probability were evaluated from the best current study by evidence
      based radiology. RESULTS: Best evidence was retrieved in ten articles from 1992
      to 2007. The best evidence level was 1b and the strength of the evidence
      included: sensitivity 0.63 (0.51, 0.76), specificity 0.97 (0.92, 1.00), positive
      predictive value 0.95, negative predictive value 0.72, positive LRs 18.37 and
      negative LRs 0.38. The gold standard of discogenic LBP is the provocative
      discography. CONCLUSIONS: For suspected discogenic LBP, HIZ is limited for the
      diagnosis if HIZ is positive, which suggests further discography. In contrast HIZ
      is a good test for diagnosis if HIZ is negative, which indicates the disease can
      be excluded.

PMID- 20137503
TI  - Current status of adult-to-adult living donor liver transplantation: surgical
      techniques and innovations.

PMID- 20137504
TI  - Indoleamine 2,3-dioxygenase in tumor induced tolerance.
AB  - OBJECTIVE: To review the recent studies about the role of indoleamine 2,3
      dioxygenase (IDO) in tumor induced tolerance. DATA SOURCES: Published articles
      (1978 - 2009) on IDO and tumor induced tolerance were selected from Medline.
      STUDY SELECTION: Articles selected were relevant to development of IDO in tumor
      induced tolerance. Of all originally identified articles, 50 specially addressed
      the stated purpose. RESULTS: Recent work has revealed IDO at high levels in
      tumors and in tumor-draining lymph nodes and a close relationship between IDO
      activity and the regulatory T cells. CONCLUSION: Up-regulation of IDO is proven
      to be a mechanism of acquired tolerance in tumors, in which the closely coupled
      positive feedback system between IDO and regulatory T cells may be considered to
      play an important role.

PMID- 20137505
TI  - Overexpression of leptin and leptin receptors in breast cancer positively
      correlates with clinicopathological features.

PMID- 20137506
TI  - A new variant of the ATP13A2 gene in Chinese patients with early-onset
      parkinsonism.

PMID- 20137507
TI  - Transsphenoidal approach to pituitary adenoma: surgical technique of the Peking
      Union Medical College Hospital.

PMID- 20137508
TI  - Multiple primary malignancies including colon, stomach, lung, breast, and liver
      cancer: a case report and literature review.

PMID- 20137509
TI  - Inflammatory myofibroblastic tumor in lung with osteopulmonary arthropathy.

PMID- 20137510
TI  - Coronary aneurysm and very late stent thrombosis formation associated with
      sirolimus-eluting stent implantation.

PMID- 20137511
TI  - Endovascular stenting in isolated dissection of superior mesenteric artery.

PMID- 20137512
TI  - Severe crush syndrome complicated with acute pancreatitis: a case report and
      review of the literatures.

PMID- 20137513
TI  - [Deepen the intervention, widen the effects of HIV/AIDS control in China].

PMID- 20137514
TI  - [Genetic characteristics of HIV-1 primary drug resistance-associated mutations in
      treatment-naive individuals in Liaoning province, 2004-2008].
AB  - OBJECTIVE: To investigate the HIV-1 drug resistance associated mutations and
      examine the susceptibility of HIV-1 with these mutations to antiretroviral in
      treatment-naive individuals in Liaoning province from 2004 to 2008. METHODS: RNA
      was extracted from 20 plasma samples of diagnosed untreated HIV-1-infected
      treatment-naive patients by drawing method. After the viral loading (VL) test,
      the protease and nucleoside reverse transcriptase coding regions were amplified
      by RT-PCR, nested PCR and sequence analysis directly. Levels of resistance and
      prevalence were evaluated according to the Stanford University HIV Drug
      Resistance Database's algorithm (http://hivdb.stanford.edu). RESULTS: Among the
      20 plasma samples, 13 got PCR products because of their VL values higher than
      1000 copies/ml.Meanwhile, the 13 samples got 65 sequences by using 5 primers
      each. Polymorphisms in subtype H and circulating recombinant forms (CRFs)
      CRF10_CD sequences were identified. An overall prevalence of 30.8% (4/13)
      resistance to NNRTIs, 7.7% (1/13) to PI and no NRTIs mutations were found. The
      most frequent substitutions (4/13) in the RT region at positions P225H, K238S,
      V179D, K238T and a major position I54S in PR implied to a multiple drug
      resistance. A71V or L10V only, respectively, substitution in PR was found in 3
      samples, but no any worse with drug sensitivity. CONCLUSION: HIV-1 polymorphisms
      in subtype H and CRFs CRF10_CD sequences were identified circulating in Liaoning.
      A major mutation position I54S in PR implied that it would be the time to
      commence a higher level drug regimen.

PMID- 20137515
TI  - [Study on the transmission of drug resistant human immunodeficiency virus-1 in
      Henan province].
AB  - OBJECTIVE: To survey the prevalence of HIV-1 drug resistance after five years
      antiretroviral treatment in Henan province. METHODS: Through the cross-sectional
      study, serum specimens of 69 HIV infected individuals that were 2 to 25 years old
      who were newly diagnosed according the WHO standard from November 2007 to August
      2008 and did not receive antiretroviral treatment (ART) were collected. HIV-1 pol
      genetic mutations associated with drug resistance were identified with RT-PCR and
      interpreted. RESULTS: Out of 69 samples, 50 samples were successfully amplified
      and sequenced. Seven drug resistant mutation in reverse transcriptase region were
      detected and three mutations in protein region. In one specimen, a mutation
      (K103N) in reverse transcriptase was identified which caused high level
      resistance to NNRTIs, but no proteinase inhibitor mutation was found in protein
      region. According to the sampling and threshold surveillance criteria, the
      prevalence of drug resistant HIV-1 in Henan was less than 5%. CONCLUSION: The
      prevalence of drug resistant HIV-1 was still at low level in Henan. However, the
      proportion of resistant strains would be higher with the antiretroviral
      treatment. We should pay more attention to the transmission of resistant strains
      and continue the drug resistance surveillance.

PMID- 20137516
TI  - [Research on co-infections of HIV and human herpesvirus-8 among the Uygur high
      risk groups in a city, Xinjiang].
AB  - OBJECTIVE: To research the co-infections of HIV and human herpesvirus 8 (HHV8) in
      Uygur high-risk groups of HIV infection in a city Xinjiang. METHODS: All 468
      Uygurs at high HIV risk registered in the sentinel monitoring system in 2006 were
      enrolled in this study. The antibodies to HHV8 latency-associated nuclear
      antigens 1 (LANA1), lytic antigens open reading frame 65 (ORF65) and K8.1 were
      measured by enzyme linked immunosorbent assay (ELISA). Chi-square test and non
      condition Logistic regression model were used for data analysis. RESULTS: Of 468
      sera samples, 67 (14.3%) were HIV and HHV8 co-infection positive.Male's HIV and
      HHV8 co-infection rate (22.6%, 54/239) was higher than the female's (5.7%,
      13/229) (chi(2) = 27.285, P < 0.001). For those above 24 year old, HIV and HHV8
      co-infection rate (15.8%, 65/412) was higher than the < 24 year old group's
      (3.6%, 2/56) (chi(2) = 5.987, P = 0.014). The group of Elementary school and
      illiterate people's HIV and HHV8 co-infection rate (20.7%, 40/193) was higher
      than the junior middle school and the above culture (9.8%, 27/275) (chi(2) =
      10.999, P = 0.001). For the unmarried people, the co-infecting rate of HIV and
      HHV8 for the married, the cohabitants, the divorced or the widowers were 16.9%
      (14/83), 12.2% (42/345), 27.5% (11/40) respectively. There was significantly
      statistical difference among three marital status (chi(2) = 7.399, P = 0.025).
      Injecting drug users' HIV and HHV8 co-infection rate (26.5%, 50/189) was higher
      than non-injecting drug users' (6.1%, 17/279) (chi(2) = 38.083, P < 0.001), and
      stratified by gender, OR(M-H) was 4.207 (95%CI: 1.529 - 11.578). Via non
      condition logistic stepwise regression analysis, only injecting drug use entered
      model, compared with non-injecting drug users, injecting drug users were more
      dangerous for HIV and HHV8 co-infecting (OR = 5.544; 95%CI: 3.081 - 9.975).
      CONCLUSION: The HIV and HHV8 co-infection rate was higher in the Uygurs at high
      HIV risk in Xinjiang. Injecting drug use is a risk factor of the HIV and HHV8 co
      infection, which might be one of routes of HIV and HHV8 co-infection among this
      group.

PMID- 20137517
TI  - [Study on the characteristics of sexual networks for men who have sex with men
      recruited at different sites in Harbin].
AB  - OBJECTIVE: To identify the characteristics of the sexual networks and HIV/AIDS
      related high-risk behaviors among MSM in Harbin city, and to evaluate the
      possibility of HIV transmission among MSM and from MSM to general population.
      METHODS: A face to face questionnaire investigation was conducted among 673 MSM
      aged above 18 years older from May to July, 2006 in Harbin, Heilongjiang
      province. The Key-informant sampling and time-location sampling methods were used
      at different sites to recruit objectives, including bars, bathrooms, parks and
      social networks.Mixing matrices were computed based on the demographic
      characteristics of MSM and their sexual partners. Sexual networks analysis by
      egocentric methods, such as network size, density and sexual mixing patterns.
      RESULTS: A total of 647 questionnaires were completed. The number of them
      recruited from bars, bathrooms, parks and social networks were 229, 291, 36 and
      91. The average size of sexual networks was 14 persons, the least network density
      was 0.14. The proportion of having sexual relationship in the past year was 30.5%
      (647/2123). Of which recruited at bars, bathrooms, parks and social networks, the
      proportions of having long-term relationship with their sex partners were 22.8%
      (159/699), 35.9% (329/917), 26.4% (28/106) and 32.7% (131/401), respectively.
      There was statistical significance in MSM having sexual relationship with their
      partners at different recruited places (chi(2) = 34.07, P < 0.01). Sexual
      networks of MSM from public bathroom was larger with an average number of 18.
      Only 35.9% (329/917) of them had long-term relationship with their sex partners.
      A tendency for age and marriage pairing to cluster around main diagonal
      suggesting that MSM were similar to choosing sexual partners in the respect of
      age and marriage status. The proportions of consistent condom use in the past 6
      months were 40.9% (647/2123). CONCLUSION: MSM from different sites have greatly
      different sexual networks characteristics. Sexual mixing patterns are weakly
      assertive in the MSM and potential of HIV spread among MSM exists.

PMID- 20137518
TI  - [Intervention trial on HIV/AIDS among men who have sex with men based on venues
      and peer network].
AB  - OBJECTIVE: To determine feasibility and effectiveness of the intervention on
      HIV/AIDS among MSM based on venues and peer network. METHODS: The intervention
      trial was conducted in Mianyang and Yibin in Sichuan province, where the cultural
      and social environment were similar. These two cities have no HIV/AIDS
      intervention conducted yet before this study. The intervention was conducted in
      Mianyang, while Yibin was regarded as control, in which education materials
      related HIV/AIDS and VCT service were available. Intervention in Mianyang
      included MSM venue intervention distributing the education materials, condom and
      promoting HIV-test and STIs clinic referral by 40 MSM as Popular Opinion Leaders
      who received the knowledge and intervention skill training.Meanwhile, Popular
      Opinion Leader intervention was implemented in MSM peer network to advocate safe
      sex. After 6-month intervention the survey was conducted to assess the
      effectiveness of intervention. RESULTS: The scores of knowledge related HIV/STDs
      and self-efficacy of condom use was 1.293 (95%CI: 0.657 - 1.292, P < 0.05) and
      1.556 (95%CI: 0.656 - 2.456, P < 0.05) higher in post-intervention than in pre
      intervention which was (12.42 +/- 0.232) and (10.25 +/- 0.327) respectively in
      Mianyang, while no significant changing in Yibin during the time. Score of
      knowledge related HIV/STDs increase 0.577 (95%CI: -0.173 - 1.327, P > 0.05) in
      post-intervention compared with (10.40 +/- 0.412) in pre-intervention and score
      of self-efficacy of condom use decreased 0.362 from 9.86 +/- 0.547 in pre
      intervention (95%CI: -1.458 - 0.534, P > 0.05). In the six months prior to
      survey, the rate of unprotected sexual intercourse with male casual sexual
      partners in last 3 times decreased to 11.0% (22/200) (OR(adjusted) = 0.472,
      95%CI: 0.265 - 0.841, P < 0.05) from 19.5% (39/200) baseline in Manyang, while in
      Yibin that increased to 19.0% (38/200) from 17.5% (35/200) in baseline
      (OR(adjusted) = 1.153, 95%CI: 0.660 - 2.014, P > 0.05). The rate of HIV-test
      increased significantly from 9.0% (18/200) to 22.0% (44/200) (OR = 2.852, 95%CI:
      1.583 - 5.138, P < 0.05) in intervention city and Accordingly in the control,
      that was 24.5% (29/200) in baseline and 24.0% (28/200) in post-intervention (OR =
      0.960, 95%CI: 0.548 - 1.682, P > 0.05). No difference was found in number of male
      sexual partner pre- and post-intervention both in intervention and control city.
      CONCLUSION: The intervention based on MSM venues and peer network among MSM is
      feasible and can increase knowledge related HIV/STDs and self-efficacy and as
      well as condom use and HIV testing.

PMID- 20137519
TI  - [Evaluation of effect of community-based HIV/AIDS interventions among men who
      have sex with men in eighteen cities, China].
AB  - OBJECTIVE: To evaluate the effect of a community-based intervention project among
      men who have sex with men (MSM) after two-year implementation. METHODS:
      Comprehensive interventions among MSM in 18 cities of seven provinces were
      conducted. The pre-intervention questionnaire was conducted in September 2006 and
      5178 subjects were investigated through snowball method. In May 2007, post
      questionnaire was conducted and 5460 subjects were investigated through snowball
      or accompanied recommendation method. For each subject, a questionnaire was
      completed, including basic information, HIV/AIDS knowledge, behaviours and
      intervention status. At the same time, 5 ml intravenous blood sample was
      collected to detect HIV infection and evaluated the intervention effect. RESULTS:
      After two-year implementation, the awareness rate of HIV/AIDS knowledge increased
      from 76.0% (3933/5178) in 2006 to 90.5% (4943/5460) in 2008 (chi(2) = 451.786, P
      < 0.001); the rate of condom use in the last anal sex with males increased from
      58.0% (2382/4105) to 76.7% (3643/4750) (chi(2) = 215.491, P < 0.01); the rate of
      consistent condom use in the last six months increased from 28.2% (1163/4118) to
      44.5% (2114/4753) (chi(2) = 264.606, P < 0.01); the proportion of MSM receiving
      HIV antibody test increased from 18.8% (973/5170) to 39.1% (2136/5454) (chi(2) =
      530.181, P < 0.01); and the HIV infection rate increased from 2.3% (118/5178) to
      5.0% (271/5427) (chi(2) = 47.613, P < 0.01). CONCLUSION: The MSM community-based
      intervention project achieved some good results after two-year implementation and
      contributed to an increase in HIV/AIDS knowledge and safe sex.

PMID- 20137520
TI  - [HIV infection and KAP status among men who have sex with men in 14 Chinese
      cities].
AB  - OBJECTIVE: To explore the current status of HIV infection and HIV-related
      knowledge, attitude and practice (KAP) among men who have sex with men (MSM) in
      14 cities in China. METHODS: A cluster sampling method was administrated and 14
      large or medium cities were selected. The respondent-driven sampling (RDS) was
      also used to conduct a questionnaire survey in 6101 MSM. Blood specimens were
      collected for HIV and syphilis testing. RESULTS: A total of 6101 MSM were
      selected and investigated, with an HIV infection rate of 6.3% (384/6101) and a
      syphilis infection rate of 14.0% (854/6101). The proportion of MSM knowing
      correct HIV/AIDS knowledge was 59.7% (3644/6101); 6.2% (378/6101) and 11.2%
      (683/6101) of the respondents ever had buying sex or selling sex in the last six
      months respectively; the proportion of consistent condom-using each time while
      with male partners in the last month was 39.2% (2392/6101). The proportion of
      condom-using while with male partners was 65.2% (3978/6101) in the last time
      among MSM. CONCLUSION: A high HIV infection rate was observed among MSM with
      limited HIV/AIDS awareness and high risk behaviors. It is necessary to initiate a
      rapid response to prevent HIV spreading in MSM.

PMID- 20137521
TI  - [The change trend of mother-to-child transmission rate of HIV-1 during 2005-2007
      in some areas of China].
AB  - OBJECTIVE: To explore the change trend of mother-to-child-transmission (MTCT) of
      HIV-1 in some areas in China. METHODS: The investigation was conducted in 15
      counties or districts of 4 provinces in China with relatively high HIV prevalence
      from January 2005 to June 2009. The data on the death and HIV-status of the
      babies born to HIV-positive mothers from January 2005-December 2007 in research
      sites were collected through 18-month following up after they were born. RESULTS:
      During the time that the research was conducted, there were 644 babies born to
      HIV-positive mothers who were followed up for 18 months. At the end of 18 months,
      full data were collected from 550 babies, 44 babies were lost to follow-up and 50
      babies died. Among 550 babies who were followed up for 18 months, 53 babies were
      confirmed as HIV positive. The rate of MTCT of HIV-1 was 13.19% (24/182), 8.90%
      (17/191) and 6.78% (12/177) in 2005, 2006, 2007 respectively, which showed a
      descending trend yearly (chi(2) = 4.23, P < 0.05). Adjusted by the death data of
      the HIV-exposed children, it was found that during 2005-2007 the rate of MTCT of
      HIV-1 was 16.74%, 12.98%, 9.52% respectively, which was also descending year by
      year (chi(2) = 4.69, P < 0.05). CONCLUSION: Long-term, effective prevention of
      mother-to-child-transmission of HIV (PMTCT) could reduce the level of MTCT of HIV
      1 year-by-year. In addition, using death data of HIV-exposed children to adjust
      the level of MTCT of HIV-1 is valuable to grade the effect of PMTCT.

PMID- 20137522
TI  - [Analysis of prevention of mother-to-child transmission of HIV (PMTCT) work in
      Zhumadian city, 2001 - 2009].
AB  - OBJECTIVE: To analyze the current status of maternal HIV infection, mother to
      child transmission, and the work accomplishments in preventing mother-to-child
      transmission of HIV (PMTCT). METHODS: During October, 2001 to May, 2009, HIV
      voluntary consultation and examination were carried out in 339 866 pregnant women
      in the urban areas, while 594 pregnant women who tested positive were intervened,
      and interventions were also conducted among 326 babies who were born to HIV
      positive mothers, including HIV immune body examination on the babies when they
      were 12 months and 18 months old. RESULTS: A total of 594 pregnant women were
      found HIV positive, with the positive rate of 0.17% (594/339 866). And the rate
      was declining year by year. The highest rate was 0.47% (37/7837) in 2002, and the
      lowest rate was 0.12% (86/73 343) in 2008. Of the 594 positive pregnant women,
      228 (38.38%) terminated pregnancy voluntarily, 43 (7.24%) kept on pregnancy and
      317 (53.37%) parturients. Of 326 babies born by the 317 parturients, 317
      survived.298 received curbing intervention for mother to child transmission
      (PMTCT), the ratio was 94.01% (298/317). Of 224 babies who were 18 months old,
      221 accepted examination, and 7 HIV positive. The maternal infant transmission
      rate after intervention was 3.17% (7/221). CONCLUSION: Through the prevention of
      mother-to-child transmission of HIV, the HIV infection status in the pregnant
      women can be timely observed, which can effectively decrease the level of mother
      to-child transmission of HIV.

PMID- 20137523
TI  - [Influencing factors on the death of infants born to HIV infected mothers].
AB  - OBJECTIVE: To understand the influencing factors on the death of infants born to
      HIV infected mothers in areas with high prevalence of HIV/AIDS in China. METHODS:
      Based on the follow-up cohort study targeting at HIV/AIDS infected pregnant women
      and their babies initiated in 2004, a survey on the death status and influencing
      factors on the infants born to HIV/AIDS infected mothers enrolled in this cohort
      from Jan.2004 to Nov.2007 was carried out during Aug.to Nov.2008 in seven
      counties of four provinces in China. A total of 498 pairs of HIV-infected mothers
      and their infants were enrolled and their related information was collected.
      Single factor and multiple factors Cox model methods were adopted for data
      analysis. RESULTS: The total observed person-years of 498 infants was 406.22,
      among which, 45 infants died, and the mortality density was 110.78 per 1000 child
      year. A single factor Cox model showed, the pregnancy in pre-period of HIV/AIDS
      and HIV/AIDS period (RR = 1.971, 95%CI: 1.143 - 3.396), living status of the
      pregnancy (RR = 3.062, 95%CI: 1.097 - 8.550), multipara women (RR = 0.517, 95%CI:
      0.278 - 0.961), natural childbirth (RR = 0.561, 95%CI: 0.345 - 0.910), premature
      labor (RR = 5.302, 95%CI: 2.944 - 9.547), low birth weight (RR = 4.920, 95%CI:
      2.691 - 8.994), mother-child pairs taking antiretroviral drugs (RR = 0.227,
      95%CI: 0.121 - 0.428) and infants infected HIV (RR = 5.870, 95%CI: 3.232 -
      10.660) could affect the infants death. The death of HIV-exposed infants was
      influenced by various factors. The death risk of infants born to HIV infected
      mothers who were in the danger of pre-period of HIV/AIDS and HIV/AIDS period was
      greater than the infants delivered by HIV infected mothers who were in
      preclinical period of HIV/AIDS (RR = 6.99, 95%CI: 1.92 - 25.64). The death risks
      were greater in the group that the women whose CD4(+)TLC count number lower than
      200 cells/microl (RR = 2.05, 95%CI: 1.01 - 4.15). The infants whose mothers had
      no ARV treatment had higher possibility to die than the others (RR = 6.17, 95%CI:
      1.62 - 23.26). The death risk of premature delivered infants was 2.87 times of
      mature delivered infants (95%CI: 1.12 - 7.35). The death risk of HIV/AIDS
      infected infants was 9.87 times of the HIV/AIDS uninfected infants (95%CI: 3.81 -
      25.62). CONCLUSION: Some measurements including improving HIV-infected pregnant
      women's immunity, reducing mother to child transmission of HIV and premature
      birth, low birth weight are beneficial to reducing infant mortality.

PMID- 20137524
TI  - [Cost-effectiveness analysis for integrated prevention of mother-to-child
      transmission of HIV].
AB  - OBJECTIVE: To evaluate the cost-effectiveness and economic efficiency of
      integrated prevention of mother-to-child transmission (PMTCT) of HIV in four high
      incidence counties. METHODS: Data of local resource investment and total cost for
      PMTCT in 4 counties in China from 2003 to 2006 were collected. Cost analysis and
      cost-effectiveness analysis were conducted. Average costs of a confirmed HIV
      case, a prevented case and a disability-adjusted life-year (DALY) saving were
      calculated. RESULTS: Average cost of identifying one HIV-infected mother was
      yen5512. Costs of a pediatric HIV case prevention and per DALY saving were yen46
      747 and yen1870 ($231), respectively, based on the total cost perspective.
      CONCLUSION: The cost of integrated prevention of mother-to-child transmission of
      HIV was low. The PMTCT program was economical efficiency.

PMID- 20137525
TI  - [Social health status of the HIV infected and their families and relevant
      influencing factors].
AB  - OBJECTIVE: To investigate the social health status of the HIV infected and their
      families in a high HIV/AIDS prevalence village in Hunan province and to examine
      the relations of the social health status, responses and social support. METHODS:
      A total of 51 HIV infected persons (infected group), 49 family members of the
      infected (family member group) and 96 normal persons (control group) were
      surveyed by Social Health Measurement Scale-a sub-scale of Self-rated Health
      Measurement Scale (SRHMS), Social Support Assessment Scale (SSAS) and Trait
      Coping Style Questionnaire (TCSQ). RESULTS: (1) In regard to the total scores of
      social health, responding style and social support, significant differences were
      found among the infected group, the group of family members and the control group
      (62.9 +/- 18.6, 79.8 +/- 18.0, 86.5 +/- 21.3, F = 18.16; 28.7 +/- 4.3, 27.2 +/-
      5.4, 25.9 +/- 6.4, F = 5.21; 33.8 +/- 8.1, 41.0 +/- 6.6, 38.1 +/- 6.8, F = 13.23;
      P < 0.01). (2) Subjective care and support, the educational status, the marital
      status and support utilization were significant predictors to the social health
      status of the infected group (R(2) = 0.73, F = 27.78, P < 0.01). (3) Subjective
      support and negative responding style were significant predictors to the social
      health status of the group of family members (R(2) = 0.32, F = 12.35, P < 0.01).
      CONCLUSION: The HIV infected and their families have more negative responding
      style, make less use of social support and hold a inferior social health status.
      It's necessary to exert psychological intervention targeting at these population
      group.

PMID- 20137526
TI  - [HIV prevalence and its correlation among the community-based drug users in
      Dongguan in 2008].
AB  - OBJECTIVE: To understand the HIV epidemic and its correlation among the community
      based drug users in Dongguan, Guangdong province. METHODS: In 2008, 13 drug users
      were identified as seeds in Dongguan. Respondent driven sampling was applied to
      recruit community-based drug users. A structured questionnaire was used for a
      face to face interview. Intravenous blood samples were collected for the
      measurement of HIV, HCV and syphilis antibodies. RDS analysis tool (RDSAT) was
      applied for adjusting the estimates and bivariate analysis. RESULTS: A total of
      303 drug users were recruited within 15 weeks and 300 blood samples were
      collected. After RDSAT adjustment, the prevalence rates of HIV, HCV and syphilis
      were 14.7% (95%CI: 6.1% - 25.4%), 63.2% (95%CI: 55.7% - 71.7%), and 4.7% (95%CI:
      1.8% - 8.2%) respectively. The HIV prevalence rates among those who were HCV
      seropositive, migration, younger than 26 years at their first drug use, and ever
      shared needles or syringes were 22.9% (95%CI: 10.8% - 37.0%), 26.9% (95% CI:
      11.4% - 44.9%), 19.9% (95%CI: 8.3% - 35.7%), and 29.1% (95%CI: 12.3% - 45.1%)
      respectively. The proportions of the drug users who were enrolled at methadone
      maintenance treatment (MMT) of local residency, migration were 20.9% (95%CI: 4.1%
      - 44.6%), 2.3% (95%CI: 0.0% - 7.0%) respectively. CONCLUSION: The HIV epidemic
      among the community-based drug users in Dongguan is serious. Drug users who are
      HCV seropositive, migration, younger than 26 years at their first drug use, and
      ever shared needles or syringes are more likely to be HIV seropositive.

PMID- 20137527
TI  - [Data analysis of national HIV comprehensive surveillance sites among female sex
      workers from 2004 to 2008].
AB  - OBJECTIVE: To monitor the time trend of behaviors change related to HIV/AIDS
      epidemic and HIV prevalence, and to provide information and basis for
      comprehensive HIV prevention responses and evaluation of intervention
      effectiveness among female sex workers in China. METHODS: During the year of 2004
      to 2008, a series of cross-sectional surveys were conducted among female sex
      workers in community recruited in both entertainment places and in street, during
      the defined timeframe, a face-to-face interview was conducted with uniformed
      questionnaire; while, the venous blood specimen was collected. The sample size
      was 400 per site per survey. RESULTS: In 15 continuous national HIV comprehensive
      surveillance sites among female sex workers from 2004 to 2008, the median of HIV
      prevalence was 0.0%; Prevalence (median) of syphilis respectively: 0.5%, 1.8%,
      1.6%, 1.8% and 1.0%. The median of target subjects who used condom in the last
      commercial sex was: 81.8%, 80.5%, 84.6%, 87.0% and 88.9% respectively; the median
      of always used condom in commercial sex during the last month: 65.8%, 59.6%,
      60.3%, 59.8% and 73.7%. The median of awareness rate on HIV/AIDS transmission of
      female sex workers was: 74.3%, 84.1%, 65.2%, 66.0% and 74.3%. The median of
      target subjects who attended HIV VCT services were: 12.4%, 20.4%, 25.8%, 25.3%
      and 31.7%. The median of the proportion of female sex workers who reached
      intervention in last year respectively: 46.4%, 76.1%, 72.1%, 95.0% and 90.8%.
      CONCLUSION: Condom use and HIV awareness rate need to enhance further among
      female sex workers. The proportion of female sex workers who attended VCT and
      knew their HIV testing result and the proportion of female sex workers who
      reached intervention in last year both increase. HIV prevalence rate among female
      sex workers is generally low, but high risk behaviors are still alarming. It is
      necessary to take more comprehensive and effective prevention measures and
      intervention.

PMID- 20137528
TI  - [Investigation of HIV/AIDS related knowledge and attitude among 6,487 high school
      students].
AB  - OBJECTIVE: To investigate HIV/AIDS related knowledge and attitude among high
      school students in China, and to preliminarily evaluate the effects of the
      special HIV/AIDS prevention education programme. METHODS: A total of 6487 high
      school students from 24 high schools of Beijing, Zhengzhou and Tangshan were
      investigated by using questionnaire, among which, 6487 students completed the
      questionnaire (96.08%). chi(2) test, t test and one way ANOVA were used to test
      the group differences and logistic regression was employed for further analysis.
      P < 0.05 was considered as statistically significance. RESULTS: The mean
      knowledge and attitude scores of the students were separately 14.42 out of 20 and
      6.47 out of 10. Students from Tangshan had the significantly (P < 0.001) highest
      knowledge and attitude level (average score of knowledge = 15.11, average score
      of attitude = 7.21) followed by Beijing (average score of knowledge = 14.62,
      average score of attitude = 6.15) and Zhengzhou (average score of knowledge =
      13.56, average score of attitude = 6.07). The significant differences were
      observed in all except the varying attitude between Zhengzhou and Beijing
      (Knowledge comparison: t(Tangshan vs Beijing) = 0.49, P < 0.001, t(Tangshan vs
      Zhengzhou) = 1.56, P < 0.001, t(Zhengzhou vs Beijing) = 1.07, P < 0.001; Attitude
      Comparison: t(Tangshan vs Beijing) = 1.06, P < 0.001, t(Tangshan vs Zhengzhou) =
      1.14, P < 0.001, t(Zhengzhou vs Beijing) = 0.08, P = 0.282). Boys had higher
      knowledge scores (average score of knowledge = 14.61) than those of girls
      (average score of knowledge = 14.23, t = 4.22, P < 0.001) but no significant
      difference was found (average knowledge score of boys = 6.47, average knowledge
      score of girls = 6.48, t = 0.16, P = 0.869). Higher knowledge level (OR = 1.21, P
      < 0.001) and being a rural student (OR = 1.31, P < 0.001) were significantly
      associated with higher attitude level, while higher grade (OR = 0.85, P = 0.003)
      and better academic performance (OR = 0.94, P = 0.003) were negative predictors
      of attitude. CONCLUSION: The HIV/AIDS related knowledge among high school
      students in China was relatively limited and instability positive attitude under
      the pressure of social desirability. It is necessary to tailor the special
      education strategies for further education effect improvement.

PMID- 20137529
TI  - [A study of HIV/AIDS-related stigma and discrimination among former plasma donors
      in rural areas].
AB  - OBJECTIVE: To understand the types of, reasons for and sources of stigma and
      discrimination in a rural community where the majority of people living with
      HIV/AIDS (PLHA) are former plasma donors (FPDs). METHODS: Eighty local residents,
      including 20 HIV-positive villagers, 20 family members, 20 villagers from non-HIV
      positive households and 20 health workers, were selected as study subjects by
      using purposive sampling method in rural areas of Anhui Province. Face-to-face
      interviews and focus group discussions were held to collect information on
      HIV/AIDS-related stigma and discrimination and its contributing factors. RESULTS:
      Of the 80 study subjects, 1 didn't finish the survey. Of the 79 subjects who
      finished the survey, the main forms of stigma and discrimination were expanded
      stigma [81.0% (64/79)], abandonment and avoidance, stigma and discrimination in
      healthcare setting [47.4% (28/59)], loss of social support [33.3% (13/39)]. The
      level of stigma was less in village where were more HIV-positive villagers living
      and vice versa. The reasons for stigma and discrimination included: ignorance or
      misunderstanding of HIV/AIDS [57.5% (23/40)], fear of HIV/AIDS [32.5% (13/40)]
      and morality judgment toward PLHA. The majority of HIV positive participants were
      unwilling to disclose their positive status to others in order to protect their
      family members and children. CONCLUSION: Ignorance and misunderstanding of
      HIV/AIDS were main contributing factors to HIV/AIDS-related stigma and
      discrimination and it is very important to implement appropriate intervention
      programs to reduce stigma and discrimination.

PMID- 20137530
TI  - [A survey on AIDS discrimination among medical college students].
AB  - OBJECTIVE: To understand the related knowledge, discrimination attitudes toward
      HIV/AIDS among medical college students, and to provide scientific evidence for
      further HIV/AIDS anti-discrimination intervention. METHODS: By means of
      stratified cluster sampling to classes, 2844 undergraduate students were randomly
      selected from medical colleges. A self-designed and self-administered
      questionnaire survey was conducted, and SPSS 13.0 software was used for data
      analysis. RESULTS: 2501 valid questionnaires had been collected. The overall
      HIV/AIDS knowledge coverage rate of the respondents was 73.1% (1828/2501); The
      HIV/AIDS discrimination rates in different questions were varying, the
      discrimination rate of infected with AIDS by bad sex and sharing needles was
      83.1% (2078/2501) and 77.7% (1943/2501) respectively, the discrimination rates in
      term of contacting with HIV patients and their daily necessities, sharing desks,
      personal social were all exceeding 40%. CONCLUSION: The medical students held
      serious discrimination attitudes to HIV infected persons and patients; it is
      necessary to strengthen anti-discrimination education about HIV/AIDS among
      medical students.

PMID- 20137531
TI  - [Clinical importance of diastolic heart failure research].

PMID- 20137532
TI  - [What have we learned from the evolution of chronic heart failure guidelines in
      the 21st century].

PMID- 20137533
TI  - [Body mass index and prognosis in patients with systolic heart failure].
AB  - OBJECTIVE: In individuals without cardiovascular disease, elevated body mass
      index (BMI) is associated with an increased risk of death. However, in patients
      with certain chronic diseases, including heart failure, low BMI has been
      associated with increased mortality. We investigated the association between BMI
      and prognosis in patients with systolic HF. METHOD: Follow-up was made on 540
      patients (mean age 58.53 years, 84.2% men) with systolic HF (LVEF < or = 45%) and
      association between BMI and adverse cardiac events was analyzed. RESULTS: During
      a median follow-up of 24 months, 92 patients died including 87 cases of cardiac
      death and 92 patients were rehospitalized. Compared with patients with BMI higher
      than 28.0 kg/m(2), patients in lower BMI categories (BMI < or = 18.5 kg/m(2) and
      > or = 18.5 kg/m(2) < 24.0 kg/m(2)) had a graded increase in the all cause death
      rate [5.44 (1.78 - 16.66), 4.30 (1.71 - 10.82)], cardiac death rate [OR(95%CI):
      5.42 (1.77 - 16.59), 4.00 (1.59 - 10.10)], HF death rate [8.94 (2.37 - 33.74),
      4.97 (1.52 - 16.20)] and MACE rate [2.10 (1.09 - 4.07), 1.79 (1.14 - 2.82)].
      After adjustment for age, gender, LVEF and NYHA grade using cox regression
      analysis, BMI categories still significantly associated with all cause death rate
      (OR = 0.77, P < 0.05), cardiac death rate (OR = 0.78, P < 0.05) and HF death rate
      (OR = 0.79, P < 0.05). CONCLUSION: In patients with systolic heart failure, lower
      BMI was an independent predictor of increased all cause death rate, cardiac death
      rate and HF death rate.

PMID- 20137534
TI  - [Causes of death analysis in 133 congestive heart failure patients].
AB  - OBJECTIVE: To analyze the causes of death in patients with heart failure.
      METHODS: A total of 133 heart failure patients died during hospitalization in our
      hospital between January 2005 and December 2008 were enrolled in this study.
      Patients were divided to two groups: sudden death (group A, n = 73, 54.9%),
      chronic end-stage pump failure (group B, n = 55, 41.4%). The remaining 5 cases
      died of other causes were excluded from the final analysis. Clinical data
      (medical history, blood pressure, clinical manifestation, NYHA cardiac function
      class, left ventricular diameter of diastole, left ventricular ejection fraction,
      ventricular arrhythmias, drug therapy) of group A and B were analyzed. RESULTS:
      There were no significant differences in terms of medical history (including
      hypertension and diabetes), blood pressure, heart rate and the incidence of
      ventricular arrhythmia between the two groups. In group A, the NYHA functional
      class was mostly II or III grade, and LVEF value was significantly higher than
      that of group B. The incidence of angina pectoris was significantly higher in
      group A compared to group B. beta-blocker and angiotensin-converting enzyme
      inhibitor or angiotensin II receptor blocker use was also significantly higher in
      group A than in group B, however, the treatment dose was significantly lower and
      therapy duration was significantly shorter in group A than in group B. There were
      significantly less patients received statins and anti-platelet aggregation drugs
      in group A compared to group B. CONCLUSION: In our patient cohort, sudden cardiac
      death often occurred in heart failure patients with NYHA cardiac function II to
      III grade, angina pectoris, probably due to the unstable coronary plaque and less
      statins and anti-platelet drug use in these patients.

PMID- 20137535
TI  - [Efficacy of cardiac resynchronization therapy for patients with refractory
      congestive heart failure].
AB  - OBJECTIVE: To observe the efficacy of cardiac resynchronization therapy for
      patients with refractory congestive heart failure. METHODS: Thirty-one patients
      with refractory congestive heart failure received cardiac resynchronization
      therapy. Before operation, all patients received standard drug therapy (28 cases)
      or integrated with CRRT (3 cases). Coronary sinus and its branches were shown by
      direct angiography with hollow angiographic catheter (11 cases) and by balloon
      angiographic catheter (20 cases). Left ventricle and right ventricle electrodes
      were implanted to 3 patients with atrial fibrillation, 4 patients with paroxysmal
      ventricular tachycardia or ventricular fibrillation received CRT-D implantation.
      electrocardiogram, 24 hours Holter, echocardiography and physical clinical
      examinations were made at baseline, 6, 12, 18 and 24 months post
      resynchronization therapy. RESULTS: Pacemakers were successfully implanted in all
      31 patients. One patient implanted with CRT-D died of multiple organ failure on
      third day after operation, 1 patient suffered sudden cardiac death 5 months after
      therapy and 2 patients were lost to fellow up 6 and 12 months after operation,
      respectively. Results from the remaining 27 patients showed that QRS duration was
      significantly decreased (153 +/- 8.4 at baseline vs. 132 +/- 9.8 at 24 months
      follow up) and cardiac function significantly improved (LVEF 0.29 +/- 0.10 at
      baseline vs. 0.41 +/- 0.11 at 24 months follow up, P < 0.05 vs. baseline) during
      follow up compared to baseline. Malignant ventricular arrhythmia occurred in 3
      patients with CRT-D and successfully terminated and converted to sinus rhythm.
      CONCLUSIONS: Cardiac resynchronization therapy could improve cardiac function for
      patients with refractory congestive heart failure. CRT-D can effectively
      terminate the malignant ventricular arrhythmia.

PMID- 20137536
TI  - [Effects of NADPH oxidase inhibition on cardiac function and myocardial calcium
      regulatory proteins in rabbits with heart failure].
AB  - OBJECTIVE: To investigate the effects of NADPH oxidase inhibition on cardiac
      function and myocardial calcium regulatory proteins mRNA expressions in rabbits
      with heart failure (HF). METHODS: HF was induced by experimental aortic
      insufficiency and abdominal aortic constriction, HF animals were treated with
      oral apocynin (15 mg/d), a NADPH oxidase inhibitor or equal dose placebo. Eight
      weeks later, cardiac function was measured by echocardiography. Myocardial NADPH
      oxidase activity was evaluated by NADPH dependent superoxide production examined
      using superoxide dismutase-inhibitable cytochrome c reduction. Sarcoplasmic
      reticulum Ca(2+)ATPase (SERCA2a), ryanodine receptor 2 (RyR2), phospholamban
      (PLB) and sodium-calcium exchanger (NCX) were determined by RT-PCR. RESULTS:
      Rabbits with HF developed ventricular dilatation and cardiac dysfunction, as well
      as increase in myocardial NADPH oxidase activity, decreases in mRNA expression of
      SERCA2a, RyR2 and PLB, and increase in mRNA expression of NCX. Apocynin
      significantly reduced NADPH oxidase activity (P < 0.05), upregulated SERCA2a,
      RyR2 and PLB mRNA expressions (SERCA2a/GAPDH: 0.63 +/- 0.11 vs. 0.34 +/- 0.08,
      RyR2/GAPDH: 0.23 +/- 0.04 vs. 0.17 +/- 0.06, PLB/GAPDH:1.28 +/- 0.13 vs. 0.95 +/-
      0.09, P < 0.05), downregulated NCX mRNA expression (NCX/GAPDH: 0.67 +/- 0.10 vs.
      0.95 +/- 0.12, P < 0.05), and improved cardiac function [LVEF: (60.06 +/- 10.07)%
      vs. (38.87 +/- 3.31)%, LVFS: (30.12 +/- 6.56)% vs. (17.40 +/- 2.45)%, P < 0.05]
      in rabbits with HF. CONCLUSION: NADPH oxidase inhibition improves cardiac
      function possibly by preventing abnormal alterations in myocardial calcium
      regulatory proteins in failing heart.

PMID- 20137537
TI  - [Effects of losartan and simvastatin on collagen content, myocardial expression
      of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overload rat
      hearts].
AB  - OBJECTIVE: To investigate the effects of simvastatin(Sim) and losartan(Los) on
      cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1
      mRNA, TIMP-2 mRNA in pressure overloaded rat hearts. METHODS: The pressure
      overload model was induced by descending aortic constriction (DAC) in rats. SD
      rats were randomized into 6 groups (n = 20 each): normol control group, control
      sham group, DAC group, Los group (DAC + Los, 5 mg/kg), Sim group (DAC + Sim, 2
      mg/kg), Los + Sim group (DAC + Los + Sim, Los 5 mg/kg, Sim 2 mg/kg). Water, Los
      or Sim drug was administrated by gavage daily beginning from day 5 after
      operation for 30 days. Collagen was measured on Masson stained myocardial
      sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in
      left ventricle were detected by RT-PCR. RESULTS: Collagen volume fraction (CVF)
      in DAC group was significantly higher than the normal control and sham groups (P
      < 0.01) which could be significantly reduced by Los and Sim (P < 0.05),
      especially in DAC + Los + Sim group (P < 0.01). The levels of myocardial MMP-2
      mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in
      DAC group than in normal control and sham groups (P < 0.01). Treatment Sim and
      Los alone and especially in combination significantly decreased the TIMP-1 mRNA,
      TIMP-2 mRNA expressions (P < 0.01) while MMP-2 mRNA, MMP-9 mRNA levels remained
      unchanged (P > 0.05). CONCLUSION: Upregulation of myocardial MMP-2 mRNA, MMP-9
      mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial
      fibrosis in this model, Sim and Los significantly inhibited myocardial fibrosis
      possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in
      this model.

PMID- 20137538
TI  - [Cardiac manifestations of patients with mitochondrial disease].
AB  - OBJECTIVE: To analyze the cardiac manifestations of mitochondriopathy patients.
      METHODS: We retrospectively analyzed the clinical (Electrocardiogram, Holter
      monitoring, echocardiogram and laboratory examinations) and pathological data of
      90 mitochondriopathy patients diagnosed within recent 20 years. The cardiac
      involvement data from these patients were summarized. RESULTS: Hypertrophic
      cardiomyopathy was found in 2 patients and dilated cardiomyopathy in 3 patients
      Mitochondriopathy diagnosis was made in 1 patient two years after heart
      transplantation due to heart failure resulting from previously diagnosed
      hypertrophic cardiomyopathy with noncompaction. The prevalence of cardiomyopathy
      is 5.6% (5/90). The prevalence of various arrhythmias was 22.2% (20/90). Four
      patients received permanent pacemaker because of Adams-Stokes attack or
      bradyarrhythmias (mitochondriopathy diagnosis was made 1-3 years post pacemaker
      implantation in 3 cases). History of syncope, respiratory failure, RBBB, atrial
      fibrillation and episodic ventricular tachyarrhythmias were presented in 1
      patient with mitochondriopathy, another mitochondriopathy patient developed
      atrial tachyarrhythmias. Arrhythmia were present in 14 mitochondriopathy patients
      including RBBB, bifascicular block, intraventricular block, Wolff-Parkinson-White
      syndrome and short PR interval syndrome. The mtDNA 3243A-G mutation was detected
      in 8 patients. CONCLUSIONS: Incidence of cardiomyopathy, heart failure and severe
      arrhythmias is high in patients with mitochondriopathy. Therefore, young
      cardiomyopathy patients with severe conduction block disorders should undergo
      relevant etiologic and genetic screening for mitochondriopathy and patients with
      diagnosed mitochondriopathy should regularly receive electrocardiogram and
      echocardiography examinations for possible cardiac involvement.

PMID- 20137539
TI  - [Increased serum apolipoprotein A5 in patients with acute coronary syndrome].
AB  - OBJECTIVE: To explore the relationship between serum apolipoprotein A5 (ApoA5)
      and lipid profile or high sensitive C-reactive protein (hs-CRP) in patients with
      acute coronary syndrome (ACS). METHODS: Serum apoA5 and hs-CRP levels were
      measured by ELISA and immunoturbidimetry in control subjects (n = 232), patients
      with stable angina (SA, n = 127), unstable angina (UA, n = 116) and acute
      myocardial infarction (AMI, n = 112). Triglyceride (TG), total cholesterol (TC),
      high density lipoprotein cholesterol (HDL-C) and low density lipoprotein
      cholesterol (LDL-C) were also measured. RESULTS: Compared with controls [(108.7
      +/- 23.2) microg/L] and SA patients [(78.3 +/- 20.2) microg/L], serum ApoA5 level
      was significantly increased in UA [(340.6 +/- 63.5) microg/L] and AMI patients
      [(373.2 +/- 73.8) microg/L] (all P < 0.05). ApoA5 was positively correlated with
      TG (r = 0.63 and 0.67, respectively, all P < 0.05) and hs-CRP (r = 0.57 and 0.55,
      respectively, all P < 0.05) in UA and AMI patients but there were no significant
      correlations between ApoA5 and TC, HDL-C and LDL-C in ACS patients (all P >
      0.05). CONCLUSION: Increased serum apoA5 level and the positive correlation
      between ApoA5 and serum TG and hs-CRP in ACS patients might reflect increased
      inflammation responses in ACS patients.

PMID- 20137540
TI  - [Effects of atorvastatin, alone and in combination with probucol on endothelial
      function in patients with acute coronary syndrome].
AB  - OBJECTIVES: To evaluate the effects of combined atorvastatin and probucol use on
      endothelial function in patients with acute coronary syndrome (ACS). METHODS:
      Thirty patients with ACS were randomized to receive atorvastatin (20 mg/d) and
      probucol (500 mg/d, combination group, n = 15) or atorvastatin (20 mg/d) alone
      (atorvastatin group) within 24 h after admission for 4 weeks. Endothelium
      dependent flow-mediated dilatation (FMD) and endothelium-independent sublingual
      nitroglycerin-mediated dilatation (NMD) as well as the levels of lipids and C
      reactive protein were assessed at baseline, 1 week and 4 weeks after therapy.
      RESULTS: Compared to baseline, the levels of total cholesterol, LDL-C and C
      reactive protein were significantly reduced after 1 week and 4 weeks in both
      groups, FMD equally increased after 1 week in both groups (atorvastatin group:
      3.75% +/- 0.78% vs. 1.09% +/- 0.44%, combination group: 3.67% +/- 0.36% vs. 1.24%
      +/- 0.37%, P < 0.01). Post 4 weeks therapy, FMD increase was significantly higher
      in combination group (3.67% +/- 0.36% at 1 week vs. 6.85% +/- 0.64% at 4 weeks, P
      < 0.01) than that in atorvastatin group (3.75% +/- 0.78% vs. 3.80% +/- 0.31%, P =
      0.954). NMD also equally and increased over 4 weeks in two groups (P < 0.01 vs.
      baseline). There was no correlation between the change in FMD/NMD and the changes
      in lipids or C-reactive protein levels. CONCLUSIONS: The combined atorvastatin
      and probucol therapy early after ACS is superior to atorvastatin alone on
      improving endothelial function.

PMID- 20137541
TI  - [Emotional disorder in patients with acute or stable coronary heart disease].
AB  - OBJECTIVE: To compare the incidence of emotional disorder in patients with acute
      or stable coronary heart disease. METHODS: A total of 298 patients with suspected
      coronary heart disease (CHD) were designed into three groups based on of coronary
      angiography results: acute coronary syndrome (ACS, n = 128), stable angina
      pectoris (SAP, n = 108) and non-CHD (n = 62). All patients were evaluated by Zung
      Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale(SAS) and
      Hamilton Depression Rating Scale (HRSD) for depression and anxiety before
      coronary angiography (CAG), 3 days after CAG, and 1 day before discharge.
      RESULTS: Incidences of depression and anxiety were significantly higher the ACS
      group (65.6%and 78.9% before CAG; 60.9% and 70.3% 3 days post CAG; 45.3%and 64.8%
      before discharge) compared patients with SAP (18.5% and 26.9% before CAG; 17.6%
      and 28.7% 3 days post CAG; 15.7% and 26.9% before discharge, all P < 0.05 vs.
      ACS) and non-CHD patients (32.3% and 25.8% before CAG; 27.4% and 24.2% 3 days
      post CAG; 29.0% and 30.6% before discharge, all P < 0.05 vs. ACS) while the
      depression and anxiety incidences were similar between patients with SAP and non
      CHD in this cohort (P > 0.05). CONCLUSION: Emotional disorder is common in
      patients with suspected heart diseases, especially in patients with ACS.
      Psychological distress of patients with suspected heart disease should be
      evaluated and treated.

PMID- 20137542
TI  - [Perindopril, amlodipine and telmisartan improve arterial stiffness in patients
      with hypertension].
AB  - OBJECTIVE: To investigate the effect of perindopril, amlodipine and telmisartan
      on improving the artery stiffness in patients with hypertension. METHODS:
      Patients with primary hypertension were randomly assigned to perindopril (4
      mg/day), Amlodipine (5 mg/day) and telmisartan (80 mg/day) regimen for 3 months
      (n = 34 each). Brachial-ankle pulse wave velocity (baPWV) was measured by an
      automatic brachial ankle pulse wave velocity device before the treatment, one
      month and three-month after the treatment. RESULTS: (1) SBP, DBP and PP were
      significantly decreased in all three groups (P < 0.001). There were no
      significant changes in HR in all three groups (P > 0.05). (2) BaPWV was
      significantly decreased in all three groups. In the perindopril, Amlodipine,
      telmisartan group, baPWV was (1859 +/- 492) cm/s, (1780 +/- 335) cm/s, (1859 +/-
      337) cm/s before the treatment; was (1757 +/- 508) cm/s, (1647 +/- 285) cm/s,
      (1632 +/- 261) cm/s one-month after the treatment; was (1702 +/- 538) cm/s, (1559
      +/- 288) cm/s, (1566 +/- 326) cm/s three-month after the treatment. Compare the
      baPWV one-month after the treatment to before the treatment P < 0.001; Compare
      the baPWV three-month after the treatment to before the treatment P < 0.001;
      Compare the baPWV three-month to one-month after the treatment perindopril group
      and telmisartan group P < 0.01, amlodipine group P < 0.001. (3) The changes of
      baPWV in one or three months were significantly more in the telmisartan group
      than in the perindopril and amlodipine groups (1 months P < 0.01, 3 months P <
      0.05). The change of baPWV was significantly greater in three months than in one
      montin in all three grops (P < 0.01). CONCLUSION: Arterial stiffness of
      hypertensive patients was improved post Telmisartan, amlodipine and perindopril
      therapy in proportion to therapy duration. Telmisartan is superior to amlodipine
      and perindopril on improving arterial stiffness of hypertensive patients.
      Continuous anti-hypertensive treatment with telmisartan, amlodipine and
      perindopril will have a persistent improvement of the artery flexibility.

PMID- 20137543
TI  - [Echocardiographic evaluation of left ventricular geometry and function in
      maintenance hemodialysis uremic patients].
AB  - OBJECTIVE: To assess left ventricular (LV) geometry, LV diastolic and systolic
      function in maintenance hemodialysis uremic patients. METHODS: Forty uremic
      patients and forty-five normal subjects were included in this study. LV volume,
      LV mass index (LVMI), relative wall thickness (RWT), LV mass and diastolic volume
      ratio (LVM/EDV) were measured. Mitral flow E velocity and A velocity ratio,
      deceleration time, mitral flow E velocity and mitral annulus Ea velocity ratio
      (E/Ea), pulmonary vein flow S velocity and D velocity ratio, atrial flow reversal
      velocity of pulmonary vein flow, mitral inflow propagation velocity, left atrium
      volume (LAV) and pulmonary artery systolic pressure (PASP) were determined for
      diastolic function evaluation. LV ejection fraction (LVEF) and single volume (SV)
      were derived from 3D echocardiography, systolic velocity of mitral valve annulus
      (Sa) by pulse tissue Doppler imaging (TDI) were used to evaluate systolic
      function. The time to peak systolic velocity (Ts) and early diastole velocity
      (Td) of LV 12 segments were measured using TDI. The maximal difference of Ts and
      Td (Ts-Dif and Td-Dif) were calculated to assess LV systolic and diastolic
      asynchrony. RESULTS: RWT, LVMI and LVM/EDV were significantly increased in uremic
      patients. There were 50% concentric, 17.5% eccentric hypertrophy and
      17.5%concentric remodeling, respectively in uremic patients. The indices for LV
      diastolic function (E/Ea, LAV and PASP) were significantly higher in uremic
      patients than those in control subjects (P < 0.01). About 85% of the diastolic
      dysfunction in uremic patients presented as impaired relaxation pattern and 32.5%
      as increased filling pressure. LVEF and SV were similar between uremic patients
      and control subjects. Sa was significantly lower in uremic group than that in
      controls (P < 0.05). Ts-Dif was similar between the 2 groups while Td-Dif was
      significantly higher in uremic patients than control subjects (P < 0.05).
      CONCLUSION: LV hypertrophy, LV mass increase and LV diastolic dysfunction were
      the major characteristic of myocardial injury in uremia patients.

PMID- 20137544
TI  - [Postoperative follow up of patients with complete atrioventricular septal
      defect].
AB  - OBJECTIVE: To observe the operative efficacy of patients with complete
      atrioventricular septal defect (CAVSD). METHODS: From January 2003 to June 2006,
      CAVSD patients underwent operative closure were included in this study. Color
      Doppler with apical four-chamber view was used to evaluate the degree of valve
      insufficiency before surgery and 2 days, 1 month, 6 months and 1 year after the
      surgery. Cardiac catheterization was performed to evaluate pulmonary artery
      pressure and pulmonary arteriolar resistance (PAR) before surgery in patients
      whose age were over 6 months. The time of staying at ICU, ventilation time after
      surgery and the occurrence of pulmonary artery hypertension crisis were recorded.
      RESULTS: 105 CAVSD patients underwent operative closure were enrolled in this
      study. The mean staying time at ICU was (4.7 +/- 2.4) days, and the mean
      ventilation time was (1.7 +/- 1.0)days, 9 patients (8.5%) developed pulmonary
      artery hypertension crisis after surgery. Patients with PAR > 8 Wood unit were
      older, staying time at ICU and ventilation time were longer compared patients
      with PAR < 8 Wood unit (all P < 0.05). The incidence of pulmonary artery
      hypertension crisis after surgery was also significantly higher in patients with
      PAR > 8 Wood unit compared patients with PAR < 8 Wood unit (P < 0.05). Hospital
      mortality was 3.8% (4/105). Three out of 4 hospital-dead patients had severe
      hypoplasia of the atrioventricular valve. Compared with preoperative, degree of
      valve insufficiency in both sides were relieved after surgery (P < 0.05). The
      valve insufficiency remained unchanged in 81 patients (77.1%), worsened in 14
      patients (13.3%) and improved in 10 patients (9.6%) after surgery. CONCLUSIONS:
      Our results suggested that early surgical repair for CAVSD was safe and
      beneficial. Preoperative PAR > 8 Wood unit was associated with increased risk of
      pulmonary artery hypertension crisis after surgery in patients with CAVSD.

PMID- 20137545
TI  - [The study of inhibiting heart rate and rapidly terminating atrial flutter of
      ibutilide on canine].
AB  - OBJECTIVE: To observe the electrophysiological effects of ibutilide on canine and
      to explore the potential mechanisms of ibutilide on terminating atrial flutter.
      METHODS: Eighteen mongrel dogs were anesthetized and intubated. The heart was
      exposed through thoracotomy for electrodes implantation. The electrophysiologic
      variables (heart rate, the conduction of intraatrium and interatrium, the
      conduction ratio of isthmus, the effective refractory period) were measured in
      the absence or presence of ibutilide (10 minute infusion with 0.10 mg/kg
      ibutilide, 30 minutes later with a maintaining dose of 0.01 mg/min). RESULTS:
      Ibutilide significant suppressed sinus atrial node function, the peak effect was
      observed at 20 - 30 min post drug infusion and heart rate returned to normal at 2
      hours post infusion. Post ibutilide infusion, 1 canine developed sinus pause for
      5 seconds and 2:1 atrioventricular conduction block was evidenced in another
      canine. The atrial, ventricular and pulmonary vein effective refractory periods
      were all significant prolonged (all P < 0.05) post ibutilide infusion. However,
      conduction of intraatrium, interatrium and isthmus remained unchanged post
      ibutilide infusion (all P > 0.05). CONCLUSIONS: Ibutilide could suppress sinus
      atrial node and the atrioventricular node function. The mechanism of ibutilide on
      rapidly terminating atrial flutter might be related to the prolongation of the
      refractory periods which might then result in the reduction of the whole
      excitable gap of the reentrant circuit and induce proceed inability of reentrant
      wavefront.

PMID- 20137546
TI  - [Autoradiography reporter gene (Ad5-tk carrying HSV1-tk gene) expression imaging
      in rat myocardium].
AB  - OBJECTIVE: Radionuclide imaging of reporter gene expression holds promise for
      noninvasive monitoring of gene therapy. Herpes simplex virus 1-thymidine kinase
      (HSV1-tk) has been successfully applied to the tumor tissue.We explored the
      feasibility of the expression imaging of HSV1-tk reporter gene in rat myocardium
      by using SPECT reporter probe (131)I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl
      5-iodouracil ((131)I-FIAU) and autoradiography (ARG). METHODS: The recombinant
      Ad5-tk carrying HSV1-tk gene and adenovirus (Ad5-null) as vector were constructed
      and intramyocardially injected into SD rats. Experiment was grouped for different
      aims as follows: (1) Influence of time on the imaging after transfection reporter
      gene: rats were injected with (131)I-FIAU at day 1, 2, 3, 5 and 7 after
      transfection of 1 x 10(8)pfu Ad5-tk; (2) Influence of various titers on the
      imaging: rats underwent intramyocardial injection with various titers of Ad5-tk
      (5 x 10(8), 1 x 10(8), 5 x 10(7), 1 x 10(7)pfu). After 2 days, rats were injected
      with (131)I-FIAU in tail vein. Equal volume Ad-nulls was intramyocardially
      injected to control rats. Rats were killed 24 h after injection of (131)I-FIAU
      and the hearts were rapidly dissected for gamma counts measurement. The total
      myocardial (131)I-FIAU accumulation was quantified in percent of injected dose
      per gram myocardium (%ID/g). The myocardial reporter gene expression was semi
      quantitatively determined by ARG and RT-PCR. RESULTS: ARG and RT-PCR showed that
      the local expression of reporter gene increased in proportion with increasing
      titer and decreased in proportion with time post injection. The semi-quantitative
      assay showed there were significant correlations among %ID/g, RT-PCR and ARG:
      r(2) = 0.963, P < 0.05 for RT-PCR and ARG; r(2) = 0.996, P < 0.01 for %ID/g and
      ARG in rats received various reporter gene titers at identical time point post
      injection; r(2) = 0.950, P < 0.05 for RT-PCR and ARG; r(2) = 0.980, P < 0.01 for
      %ID/g and ARG for rats received identical reporter gene titer on various time
      points post injection. CONCLUSIONS: The present study showed that cardiac
      reporter gene imaging with HSV1-tk as reporter gene and (131)I-FIAU as reporter
      probe was feasible in rats. The optimal Ad5-tk titer is 1 x 10(8) pfu and the
      optimal imaging time is 24 h to 48 h post gene transfer. HSV1-tk/FIAU may be used
      for the noninvasive monitoring of cardiac gene therapy.

PMID- 20137547
TI  - [Eukaryotic expression vector pcDNA3-HERG transfection inhibits angiotensin II
      induced neonatal rabbit ventricular myocyte hypertrophy in vitro].
AB  - OBJECTIVE: To explore the effects of eukaryotic expression vector pcDNA3-HERG
      transfection on angiotensin II (Ang II) induced myocyte hypertrophy in cultured
      neonatal rabbit ventricular myocytes. METHODS: Neonatal rabbit ventricular
      myocytes and eukaryotic expression vector pcDNA3-HERG transfected ventricular
      myocytes were cultured in Dulbecco's-modified Eagle medium (DMEM), containing 1%
      fetal bovine serum (FBS) for 6 h, then stimulated with Ang II (10(-7) mol/L) for
      48 h. Control ventricular myocytes were cultured in Dulbecco's-modified Eagle
      medium (DMEM), containing 1% fetal bovine serum (FBS) for 54 h. At 6 and 54 h,
      myocyte hypertrophic parameters including myocyte volume, total protein content
      and membrane capacitance, action potential duration (APD) and Calcineurin (CaN)
      activity were measured. RESULTS: Compared to control myocytes, APD at 90%
      repolarization (APD(90)) was prolonged by 19.8% (P < 0.01), without signs of
      myocyte hypertrophy at 6 h post Ang II stimulation, APD(90) was prolonged by
      22.1% (P < 0.01), myocyte volume, total protein content and membrane capacitance
      and CaN activity were significantly increased by 40.4%, 40.4%, 38.2% and 114.7%
      respectively (all P < 0.01) at 48 h after Ang II stimulation. HERG gene
      transfection upregulated I(HERG) tail current (3.6-fold higher than I(Kr)-rapidly
      activating delayed rectifier potassium current, P < 0.01). HERG gene transfection
      also accelerated and repolarization and a shortened APD(90) and inhibited myocyte
      hypertrophy and CaN activation induced by Ang II. CONCLUSIONS: Ang II induced
      prolongation of APD(90) is directly associated with myocyte hypertrophy by
      increasing the Ca(2+) influx and resulting in the increment of intracellular
      Ca(2+) and activation of CaN reaction pathway.

PMID- 20137548
TI  - [Efficacy of a domestic left-disk-coated atrial septal occluder on treating
      patent foramen Ovale in a miniswine model].
AB  - OBJECTIVE: To evaluate the efficacy and safety of domestic left-disk-coated
      atrial septal occluder on treating patent foramen ovale in a miniswine model.
      METHODS: Foramen ovale was punctured in 12 Guangxi BA-MA miniswine and occluded
      by domestic left-disk-coated atrial septal occluder (Spider(TM) PFO closure
      system) under the guidance of fluoroscopy. After occlusion, miniswine were
      executed after transthoracic echocardiography examination with color Doppler at
      month 1, 2, 3 and 6 respectively for gross inspection and microscopic
      examinations. RESULTS: There were no vegetation, thrombosis, broken stent, or
      erosion on the surface of all devices. The PFOs were completed occluded as
      evidenced by transthoracic echocardiography at 1 to 6 months after operation. The
      surface of the device was fully covered by collagen tissue and endothelial tissue
      at 1 month after operation and the thickened gradually thereafter. CONCLUSIONS:
      The domestic left-disk-coated atrial septal occluder can efficiently occlude
      patent foramen ovale. Satisfactory biocompatibility, rapid and complete
      endothelium covering and low incidence of complication are also evidenced for
      this closure system in our experiment.

PMID- 20137549
TI  - [Cardiac symptom as major presentation of mitochondrial disease: two cases
      report].

PMID- 20137550
TI  - [High-output heart failure due to femoral arteriovenous fistula post intra-aortic
      balloon pump use: a case report].

PMID- 20137551
TI  - [Unexpected occluder dislocation after transcatheter closure of patent ductus
      arteriosus in two patients].

PMID- 20137552
TI  - [A case of acute type A aortic dissection induced anterior myocardial infarction
      due to left main coronary artery compression].

PMID- 20137553
TI  - [The chloride channels in pulmonary artery smooth muscle cells].

PMID- 20137554
TI  - [Role of the transcription factor Kruppel-like factor 4 (KLF4) in the
      pathogenesis of atherosclerosis].

PMID- 20137556
TI  - [Comparison of food safety regulation in different countries].

PMID- 20137555
TI  - [Dietary and nutritional interventions for metabolic syndrome].

PMID- 20137557
TI  - [Medium- and long-chain fatty acid triacylglycerol reduce body fat and serum
      triglyceride in overweight and hypertriglyceridemic subjects].
AB  - OBJECTIVE: To investigate effects of medium- and long-chain fatty acid
      triacylglycerols (MLCT) on body fat and serum lipid in overweight and
      hypertriglyceridemic subjects. METHODS: A double-blind, controlled clinical trial
      was carried out, in which 112 subjects with hypertriglyceridemia were enrolled
      and divided into two groups, there were 56 subjects in each group. One group was
      randomized to consume long-chain fatty acid triacylglycerol (LCT), and the other
      to MLCT. All volunteers were asked to consume 25 - 30 g test oil daily for
      consecutive 8 weeks. Anthropometric measurements of body weight, body fat weight,
      waist circumference(WC), hip circumference(HC), WHR (ratio of WC/HC), total fat
      weight, subcutaneous fat area, visceral fat area, and serum biochemical variables
      of glucose, total cholesterols(TC), triglycerides(TG), high density lipoprotein
      cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)were measured
      at the initial and final time of the study. RESULTS: 11 subjects were excluded
      from the study because of various reasons. Of the 101 included cases, there were
      50 (male subject 34, 68.0%) and 51 (male subject 33, 64.7%) subjects left in LCT
      and MLCT group respectively. The proportion of men in MLCT (64.7%, 33/51) was not
      significantly different (chi(2) = 0.1227, P > 0.05) compared to those in LCT
      (68.0%, 34/50). The average age of MLCT was (54.2 +/- 12.5) which was not
      significantly different (t = 0.39, P > 0.05) compared to those in LCT (53.2 +/-
      13.0); Body mass index (BMI) of MLCT was (25.9 +/- 3.3) kg/m(2), which was not
      significantly different (t = 0.08, P > 0.05) compared to those of LCT (25.9 +/-
      2.4) kg/m(2). After consumption of test oil for 8 weeks, extent of decrease in
      BMI, percent of body fat, subcutaneous fat, serum TG and serum LDL-C in
      overweight subjects of MLCT were (-0.73 +/- 0.61) kg/m(2), (-1.53 +/- 1.32)%, (
      16.29 +/- 19.25) cm(2), (-0.57 +/- 0.86) mmol/L and (-0.05 +/- 0.64) mmol/L
      respectively, those in overweight subjects of LCT were (-0.19 +/- 0.61) kg/m(2),
      (-0.58 +/- 1.02)%, (4.69 +/- 19.06) cm(2), (0.65 +/- 1.10) mmol/L and (0.38 +/-
      0.58) mmol/L respectively, all of them were significantly different (the value of
      t were -2.70, -2.43, -3.20, -3.81 and -2.09 respectively, all of P value were
      less than 0.05). CONCLUSION: Consumption of MLCT can reduce body fat weight and
      serum triacylglycerol and LDL-C in overweight hypertriglyceridemic subjects under
      an appropriate dietary regime.

PMID- 20137558
TI  - [Relationship study of angiotensin II type 1 receptor gene A1166C polymorphism,
      food consumption and behavior on hypertension in Kazakh group, Xinjiang].
AB  - OBJECTIVE: To investigate the polymorphism of angiotensin II type 1 receptor
      (AT(1R)) gene A1166C and environmental factors on hypertension of Kazakh people.
      METHODS: Through the random program of SPSS 13.0, 220 cases were randomly
      selected from the confirmed hypertension patients, and 220 cases with normal
      blood pressure were selected as control group. All cases were investigated
      through the questionnaire and the related indexes were measured. By polymerase
      chain reaction (PCR) method, the genotypes were determined. RESULTS: (1) In
      hypertension group, the genotype frequency of AA and AC were 78.6% (173/220) and
      21.4% (47/220), respectively, compared with control groups' 81.4% (179/220) and
      18.6% (41/220), no significant difference was identified between these two groups
      (chi(2) = 0.537, P > 0.05). In hypertension group, the frequency of A and C
      allele were 89.0% and 11.0%, respectively, compared with 90.3% and 9.7% in
      control group. There was no significant difference between these two groups
      (chi(2) = 0.37, P > 0.05). (2) AC genotype might interact with excessive salt
      consumption (hypertension group, 31/220, 15.5%; control group 10/220, 4.5%, OR:
      4.67, 95%CI: 2.15 - 10.15), overweight (hypertension group, 19/220, 8.6%; control
      group, 9/220, 4.1%, OR: 6.96, 95%CI: 2.33 - 20.76) and drinking large volume of
      salty milk (hypertension group, 20/220, 9.1%; control group, 10/220, 4.5%, OR:
      2.67, 95%CI: 1.11 - 6.42) which will raise hypertension hazard of AC genotype.
      CONCLUSION: There is no relationship between the A1166C gene polymorphism of
      AT(1R) gene and hypertension of Kazakh people. AC genotypes might also interact
      with food consumption habit and behavior factors and increase the individual risk
      of hypertension.

PMID- 20137559
TI  - [A WZS miniature swine food hypersensitivity model orally induced by soybean beta
      conglycinin].
AB  - OBJECTIVE: To establish WZS miniature swine model of beta-conglycinin (7 S)
      allergy for evaluating the potential allergenicity of genetically modified food.
      METHODS: Twelve 45-day-old WZS miniature swines from three litters were randomly
      divided into three groups (control group; 4% 7 S group and 8% 7 S group, n = 4),
      which were respectively gastric sensitized (day 0 - 10) and oral challenged (day
      6 - 18, 31) to induce anaphylactic reactions. Clinical symptoms, skin prick
      reactions were recorded. At day 10, 19 and 32, serum IgG, IgE, histamine and
      cytokines levels were measured by ELISA. RESULTS: Diarrhea at different degrees
      were observed in 4% and 8% 7 S groups. The skin erythema reactions in grade "-",
      "+/-", "+", "++" of control group respectively were 2/4, 2/4, 0/4, 0/4, of 4% 7 S
      group were 0/4, 0/4, 2/4, 2/4 and of 8% 7 S group were 0/4, 0/4, 1/4, 3/4. The
      serum IgE and histamine levels of day 11, 19 and 32 were all significantly and
      positively correlated (Pearson coefficients = 1, P = 0.000). The serum IgG, IgE
      and histamine levels all reached the peak after 7 S groups were oral challenged
      at day 19.Compared with the control group, serum IgG (lg IgG: 2.95 +/- 0.31 vs
      2.29 +/- 0.25, t = 3.19, P = 0.011), IgE (lg IgE: 2.45 +/- 0.30 vs 1.77 +/- 0.23,
      t = 3.31, P = 0.009) and histamine levels(lg histamine:2.13 +/- 0.30 vs 1.45 +/-
      0.23, t = 3.34, P = 0.009) of 4% 7 S group at day 19 were all significantly
      higher, while the serum IFN-gamma content [(35.78 +/- 6.42) pg/ml vs (51.10 +/-
      9.67) pg/ml, t = -2.33, P = 0.045] of 4%7 S group was significantly lower.
      CONCLUSION: The WZS miniature swine model orally induced by soybean beta
      conglycinin is type I hypersensitivity mediated by IgE, which can be used to
      predict the potential allergenicity of genetically modified food.

PMID- 20137560
TI  - [Risk assessment of Listeria monocytogenes in deli meats and vegetable salads].
AB  - OBJECTIVE: To analysis risk from Listeria monocytogenes in deli meats and
      vegetable salads. METHODS: Use Risk Ranger which is a software programme
      developed by the University of Hobart, Australia and answer 11 questions on
      affecting the risk from hazards in the specific foods by combining data from
      national foodborne diseases surveillance network and some references to make semi
      quantitative risk assessment for the specific food. RESULTS: Relative risk from
      Listeria monocytogenes in deli meats and vegetable salads is 61 and 52,
      respectively. Incidence of listeriosis caused by deli meats-Listeria
      monocytogenes pairs and vegetable salads-Listeria monocytogenes pairs is 5.4 and
      0.2 cases per million people, respectively. Risk from the former is 32 times than
      that from the latter. By changing the selection for some risk factors in the
      model, it was known that the risks from two food-hazard combinations could
      decrease 10 times, if taking necessary actions after processing. CONCLUSION: Deli
      meats is a kind of high risk food for listeriosis.

PMID- 20137561
TI  - [Evaluation of immunization protection efficacy of plague subunit vaccine].
AB  - OBJECTIVE: To evaluate the protective efficacy of plague subunit vaccine, BALB/c
      mice, guinea pigs and rabbits were used in this study. METHODS: Groups of mice
      (10 per group), guinea pigs (14 per group) and rabbits (6 per group) were
      immunized with F1 + rV270 vaccine, EV76 vaccine and alum adjuvant by
      intramuscular route, respectively. Serum antibody titres of mice, guinea pigs and
      rabbits were determined by ELISA and the immunized animals were challenged with
      10(6) CFU of Y. pestis strain 141 at the 8th week after the primary immunization.
      RESULTS: The immunized mice, guinea pigs or rabbits with subunit vaccine
      developed anti-F1 IgG titre of 41 587.3 +/- 2.1, 11 543.7 +/- 2.1 or 522.4 +/-
      22.4 and elicited statistical anti-F1 IgG titre difference among them (F = 17.58,
      P < 0.01). The immunized mice, guinea pigs or rabbits with subunit vaccine had
      anti-rV270 IgG titre of 15 748.7 +/- 1.6, 12.6 +/- 1.4 or 1648.0 +/- 5.0 and
      induced statistical anti-rV270 IgG titre difference among them (F value was
      16.34, P < 0.01). There was significant anti-F1 IgG titre difference among mice,
      guinea pigs and rabbits immunized with EV76 vaccine that developed anti-F1 IgG
      titre of 913.4 +/- 4.5, 937.0 +/- 2.0 or 342.0 +/- 12.0 (F = 23.67, P < 0.01),
      whereas the immunized mice, guinea pigs and rabbits with EV76 vaccine developed
      anti-rV270 IgG titre of 12.0 +/- 1.0, 447.0 +/- 10.0, 40.0 +/- 11.0 and there was
      no anti-rV270 IgG titre difference between them (F = 2.20, P = 0.1314). The
      immunized mice with subunit vaccine developed significantly higher anti-F1 IgG
      titres than immunized guinea pigs and rabbits (q value was 30.57 and 19.04,
      respectively, P < 0.01), and there were no anti-F1 IgG titre differences between
      the immunized guinea pigs and rabbits (q = 0.04, P = 0.8485). The immunized mice
      with subunit vaccine developed significantly higher anti-rV270 IgG titres than
      immunized guinea pigs and rabbits (q value was 27.10 and 19.49, respectively, P <
      0.01), and there were no anti-rV270 IgG titre differences between the immunized
      guinea pigs and rabbits with the subunit vaccine (q = 0.25, P = 0.6187). The
      immunized mice with EV76 elicited higher anti-F1 IgG titres than immunized guinea
      pigs and rabbits (q value was 40.67 and 29.10, respectively, P < 0.01), whereas
      there was no difference of F1 IgG titer between immunized guinea pigs and rabbits
      (q = 0.06, P = 0.8098). The immunized mice, guinea pigs and rabbits with subunit
      vaccine provided 100% (10/10), 86% (12/14) and 100% (5/5) protection against
      10(6) CFU Y. pestis of challenge, respectively. The immunized mice, guinea pigs
      and rabbits with EV76 vaccine gave 100% (6/6), 93% (13/14) and 100% (6/6)
      protection against 10(6) CFU Y. pestis of challenge respectively. CONCLUSION:
      BALB/c mice is the best small animal model for valuation of protective efficacy
      of plague subunit vaccine. The guinea pigs showed a high individual variation for
      this purpose. The rabbits can be used as an alternative model for evaluating
      plague subunit vaccine.

PMID- 20137562
TI  - [Etiological analysis of enteric infectious diseases during Beijing Olympic
      Games].
AB  - OBJECTIVE: To understand pathogen patterns of enteric infectious diseases and its
      impact on this pattern due to aggregation of a great deal of foreign visitors
      during Beijing Olympic Games. METHODS: The diarrheal patient's rectal swabs and
      stool specimens were collected from Olympic stadium and hospitals of four
      districts, including Dongcheng, Xicheng, Haidian and Chaoyang. Enteric multiple
      pathogens were detected from the total 45 specimens. The culture method was used
      for the enteric bacteria, ELISA and RT-PCR for the enteric viruses. Molecular
      typing of Salmonella Enteritidis isolation was completed by PFGE. RESULTS: It was
      found that 26 out of 45 cases were positive with 57.8 percent for pathogen
      detection, and 24 were identified as enteric pathogenic bacteria, including
      Vibrio parahaemolyticus, Salmonella, diarrheagenic Escherichia coli and
      Campylobacter jejuni, two as norovirus. There were mixed infections of two
      pathogenic bacteria for three cases. Ten kinds of pathogens were detected from
      foreign cases, while five kinds from Chinese cases. A total of 5 PFGE patterns
      were identified in 10 Salmonella Enteritidis isolates from national and foreign
      diarrheal cases, which were concentrative in some extent. CONCLUSION: Vibrio
      parahaemolyticus, Salmonella, diarrheagenic Escherichia coli and Campylobacter
      jejuni were found to be the primary bacterial pathogens during the Olympic Games.
      Enteric virus infection existed in summer diarrhea.

PMID- 20137563
TI  - [Variations of brain magnetic resonance imaging among manganese-exposed workers].
AB  - OBJECTIVE: Variations of the signal intensities in the magnetic resonance (MR)
      T(1)-weighted image (T(1)WI) of globus pallidus among manganese(Mn)-exposed
      workers were explored to provide a scientific basis for exposed biomarker of
      manganese-injured central nervous system (CNS). METHODS: The brain MR T(1) and
      T(2) WI in eighteen male asymptomatic Mn-exposed, eight manganism and nine
      healthy control workers were examined routinely by adopting a 1.5 Tesla signal
      superconducting system. The SIGP and the signal intensity in frontal white matter
      (SIFWM) in the same side were determined, then pallidal index (PI) was
      calculated. Concentration of MnO(2) in workplaces and content of manganese in red
      blood cell (MnRBC) among workers were respectively determined by flame atomic
      absorption spectrometer (AAS) and inductively coupled plasma-atomic emission
      spectrophotometry (ICP-AES). The follow-up investigation in the eight high Mn
      exposed workers was made one year later. RESULTS: The results showed that the
      median of air MnO(2) in smelting workplace was 0.64 mg/m(3)(0.07 - 5.40 mg/m(3)),
      which were respective 0.56 mg/m(3)(0.09 - 1.71 mg/m(3)) in power distribution
      room (low Mn-exposure) and 0.89 mg/m(3) (0.07 - 5.40 mg/m(3)) in furnace (high Mn
      exposure). PI in the Mn-exposed and high Mn-exposed workers were both higher than
      those of the manganism and control workers(116.4 +/- 8.2, 119.0 +/- 7.9, 105.3 +/
      8.4 and 102.2 +/- 1.5, respectively. Mn vs control, t' = 7.146, P = 0.000; Mn vs
      manganism, t = 3.181, P = 0.004. High Mn-exposure vs control, t' = 7.446, P =
      0.000; high Mn-exposure vs manganism, t = 3.763, P = 0.001). The increased signal
      in T(1)WI of globus pallidus was observed in Mn-exposed workers, especially in
      high Mn-exposed workers. The content of manganese in red blood cell of Mn-exposed
      and control workers was significantly higher than those of the manganism workers
      [(151.6 +/- 40.5) ng/ml, (149.2 +/- 21.3) ng/ml, (154.5 +/- 46.6) ng/ml, (144.4
      +/- 14.2) ng/ml, (20.8 +/- 7.4) ng/ml respectively. The difference was
      significant in statistics. Manganism vs control, t = 20.206, P = 0.000; manganism
      vs Mn, t' = 13.144, P = 0.000; manganism vs low and high Mn, t' = 12.964, 9.957,
      respectively, P = 0.000]. Only a decreased median of air MnO(2) in furnace was
      found one year later (0.89, 0.31 mg/m(3), Z = -2.142, P = 0.032). The difference
      was significant in statistics. CONCLUSION: Our data suggests that SIGP of MR
      T(1)WI among workers was obviously increased by manganese-exposure. PI may be
      taken as the signal of CNS injury which was induced by manganese-exposure.

PMID- 20137564
TI  - [Identification and sequence analysis of E gene of Dengue virus type 2 strain
      isolated from patient serum in Shenzhen].
AB  - OBJECTIVE: To isolate and identify the pathogen of Dengue fever from Shenzhen
      city in 2005 - 2006, and to analyze the molecular characteristics of the isolated
      Dengue virus strain as well as to explore its possible origin. METHODS: IgM and
      IgG of serum samples taken from 60 suspected Dengue fever patients were detected
      by ELISA and immunochromatography, and 9 specimens were positive. Nine samples
      from patients with early stage Dengue fever were used to isolate virus with C6/36
      cell line and the positive cell cultures were identified by MGB fluorescent PCR.
      The type of isolated virus strain was determined by RT-semi-nested-PCR and
      fluorescent PCR. E gene of isolated virus strain was amplified by RT-PCR and
      sequenced. Homology and phylogenetic tree of E gene of Shenzhen Dengue virus with
      the strains isolated from other areas were constructed. RESULTS: Of nine antibody
      positive serum samples, one strain of Dengue virus was successfully isolated. The
      isolated virus strain was confirmed as Dengue virus type 2 and designated as DEN2
      SZ0521. The homology of nucleotide sequence and the deduced amino acid sequence
      of E gene of SZ0521 with standard type 2 Dengue virus NGC strain was 94.2% and
      98.2%, but the homology with standard Dengue virus 1, 3, 4 in the same fragment
      were 59.1%, 57.2%, 58.5% and 68.1%, 66.7%, 63.2%, respectively. The phylogenetic
      tree indicated that SZ0521 had the greatest similarity with the Malay0412a/Tw
      strain and they lied in the same branch of the phylogenetic tree. The
      corresponding homology of nucleotide sequence and amino acid sequence was 99.8%
      and 100%, respectively. The isolated Dengue virus type 2 belonged to genotype IV
      with Indonesia-76, Somalia-84 and Sri Lanka-90. CONCLUSION: Dengue virus was
      isolated from Shenzhen for the first time, and it was classified as type 2. It
      was confirmed that the type 2 Dengue virus may come from the epidemic area in
      Malaysia.

PMID- 20137565
TI  - [Detection of enterohemorrhagic Escherichia coli O157:H7 by loop-mediated
      isothermal amplification].
AB  - OBJECTIVE: To develop a loop-mediated isothermal amplification (LAMP) method for
      rapidly diagnosing of Escherichia coli (EHEC) O157:H7 in pathogen detection
      department or small-scale laboratories. METHODS: Primers for LAMP test were
      designed by targeting the antigen coding rfbE of EHEC O157:H7, the Shiga-like
      toxin stx2 and the fliC encoding gene of H7 flagella antigen, respectively. The
      reaction condition and reaction system of LAMP were optimized. 2 EHEC O157:H7
      type strains, 17 local strains and 33 other enterobacteria were analyzed to
      evaluate the LAMP's specificity and sensitivity. The results of the LAMP reaction
      were also compared with routine PCR method. RESULTS: The amplification products
      of O157 which had the corresponding target genes turned green by visual
      inspection and had ladder-like pattern on the gel, but products of other
      enterobacteria remained orange by visual examination and had no band on the gel.
      The detection results of LAMP were the same as of routine PCR method. The
      reaction time of the LAMP method was only 1.5 hours and the detection limit of
      LAMP assay was 26 CFU/reaction. In addition, the LAMP results could be determined
      only by visual inspection. CONCLUSION: LAMP assay is rapid, specific, and
      sensitive for the detection of EHEC O157:H7. This method might not only reduce
      the dependence of complicated equipments but also be a potential method for wider
      use in pathogen detection department, small-scale laboratory, emergency motor
      vehicle or field survey.

PMID- 20137566
TI  - Fostering adherence to optimize therapy in asthma.

PMID- 20137567
TI  - Surgical strategy for mild ischemic mitral insufficiency.

PMID- 20137568
TI  - Advances in respiratory medicine in the mainland of China: a historical
      perspective.

PMID- 20137569
TI  - Relationship of daytime blood pressure and severity of obstructive sleep apnea
      among Chinese: a multi-center investigation in China.
AB  - BACKGROUND: Epidemiologic studies have shown an independent and definite
      association between obstructive sleep apnea (OSA) and hypertension. This study
      aimed to define the association between daytime blood pressure and severity of
      OSA in Chinese population in mainland of China. METHODS: Twenty university
      hospital sleep centers in mainland of China were invited by the Chinese Medical
      Association (CMA) to participate in this epidemiologic study and 2297 consecutive
      patients (aged 18 - 85 years; 1981 males and 316 females) referred to these
      twenty sleep centers for evaluation of OSA between January 2004 and April 2006
      were prospectively enrolled. Nocturnal polysomnography was performed in each
      patient, and disease severity was assessed based on the apneahypopnea index
      (AHI). These patients were classfied into four groups: nonapneic control
      (control, n = 257) with AHI < or = 5 episodes/hour; mild sleep apnea (mild, n =
      402) with AHI > 5 and < or = 15 episodes/hour; moderate sleep apnea (moderate, n
      = 460) with AHI > 15 and < or = 30 episodes/hour and severe sleep apnea (severe,
      n = 1178) with AHI > 30 episodes/hour. Daytime blood pressure measurements were
      performed under standardized conditions in each patient at 10 a.m. in office on
      the day of referring to sleep centers for getting average value. All the patients
      were requested to quit medications related to blood pressure for three days
      before the day of assessing. RESULTS: Both daytime systolic blood pressure and
      diastolic blood pressure values were significantly related to AHI positively (r =
      0.201 and 0.276, respectively; both P values < 0.001) and to nadir nocturnal
      oxygen saturation negatively (r = -0.215 and -0.277, respectively; both P values
      < 0.001), which were the parameters of OSA severity. In two special designed mean
      plots, means of daytime systolic and diastolic blood pressure increased gradually
      with increasing AHI. Beyond AHI of 61 - 65, this increasing trend reached a
      plateau. CONCLUSIONS: The results showed that OSA severity was associated with
      daytime blood pressure until AHI of 61 - 65, providing evidence for early OSA
      management, especially in OSA patients with concomitant hypertension.

PMID- 20137570
TI  - Endovascular embolization of pulmonary arteriovenous malformations.
AB  - BACKGROUND: The major consequence of pulmonary arteriovenous malformations
      (PAVMs) is the direct inflow of blood from the pulmonary artery to the pulmonary
      vein which induces hypoxemia. Severe complications include transient ischemic
      attacks, paradoxical embolization in the central nervous system, massive
      hemoptysis or hemothorax, etc. The conventional treatment is surgical
      intervention. However, this can be very traumatic and dangerous. Endovascular
      embolization has advantages over surgery such as a faithful therapeutic effect, a
      low complication rate, repeatability, etc. METHODS: Patients (n = 23) with
      symptomatic PAVMs underwent endovascular embolization; 11 were males and 12 were
      females, with ages ranging from 6 months to 58 years. During the embolization,
      microcoils were applied in 6 cases and standard steel coils were used in 17
      cases. RESULTS: Multiple PAVMs lesions were found in 16 cases and single PAVMs
      lesion was found in 7 cases. Embolotherapy was carried out 28 times for 23
      patients. The success rate was 100%. The results of pulmonary arteriography after
      treatment showed that single lesion disappeared completely while the main
      abnormal vessels in multiple lesions also disappeared. The mean blood oxygen
      saturation increased from (78.04 + or - 8.22)% to (95.13 + or - 3.67)% after the
      procedure. A correlated groups t test showed changes in blood oxygen saturation
      before and after embolization (t = 9.101, P < 0.001). Symptoms of cardiac
      insufficiency disappeared in 5 cases and vascular murmur in the chest disappeared
      in 13 cases. After embolization, mild chest pain occurred in 11 cases, small
      amounts of pleural effusion occurred in 5 cases, and 1 patient died 2 months
      later because of a pyogenic infection secondary to the pulmonary infarction.
      Among the 22 remaining cases, with overall follow-up ranging from 18 months to 12
      years, general conditions were fine, daily lives were normal and there were no
      neurologic symptoms or signs, except for 3 patients with diffused PAVMs who had
      persistent blood oxygen saturation between 85% and 90%. Symptoms of hypoxia never
      recurred in the other cases. CONCLUSIONS: Endovascular embolization of pulmonary
      arteriovenous malformations can significantly improve blood oxygen saturation and
      reduce serious complications such as cerebral infaction. Therefore, this kind of
      interventional procedure is a safe and effective treatment method with a low
      complication rate.

PMID- 20137571
TI  - Solid malignancies complicated with pulmonary embolism: clinical analysis of 120
      patients.
AB  - BACKGROUND: Pulmonary embolism, a potentially fatal event, occurs more frequently
      in cancer patients than in the general population. To offer an accurate diagnosis
      and effective treatment to such patients in China, we analyzed the incidence rate
      and clinical features of pulmonary embolism in patients with solid tumor
      hospitalized in the Peking Union Medical College (PUMC) Hospital. METHODS: A
      retrospective analysis was made of the hospitalized patients with solid
      malignancies complicated with pulmonary embolism who had been admitted into the
      PUMC Hospital from January 2002 to December 2008. RESULTS: The incidence of
      pulmonary embolism in hospitalized patients with solid malignancies was 0.27%
      (120/43 967). The median age at diagnosis was 57.5 years. The male to female
      ratio was 1.0:1.4 (49:71). Patients with non-small-cell lung cancer (NSCLC)
      constituted the largest proportion of the 120 patients (37.5%), followed by
      patients with breast (9.2%), ovarian (8.3%), pancreatic (6.7%), and liver cancer
      (6.7%). Eighty patients (66.7%) had stage IV cancer. Bone was the most common
      site of distant metastasis (46.3%). D-dimer level was elevated in 90.9% of the 66
      tested patients. The incidence of bleeding due to anti-coagulation therapy was
      3.6%. Thirty-six (30.0%) of the 120 patients had concurrent deep venous
      thrombosis in the lower extremities. Seventeen patients developed acute pulmonary
      embolism within 2 weeks after surgery, 3 of whom died suddenly. Four patients
      presented with deep venous thrombosis and 1 with pulmonary embolism prior to the
      identification of malignancy. CONCLUSIONS: Patients with cancer of the lung,
      ovarian, breast, pancreas, and liver are more likely to be complicated with
      pulmonary embolism than those with other types of solid tumors. Patients with
      distant metastasis are at a higher risk of pulmonary embolism. Pulmonary embolism
      without concurrent deep venous thrombosis is more frequently observed than
      concurrence of both disorders in the clinical setting.

PMID- 20137572
TI  - Detection of lung adenocarcinoma using magnetic beads based matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry serum protein profiling.
AB  - BACKGROUND: Recently, due to the rapid development of proteomic techniques, great
      advance has been made in many scientific fields. We aimed to use magnetic beads
      (liquid chip) based matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS) technology to screen distinctive biomarkers for
      lung adenocarcinoma (adCA), and to establish the diagnostic protein profiles.
      METHODS: Using weak cation exchange magnetic beads (MB-WCX) to isolate and purify
      low molecular weight proteins from sera of 35 lung adCA, 46 benign lung diseases
      (BLDs) and 44 healthy individuals. The resulting spectra gained by anchor chip
      MALDI-TOF-MS were analyzed by ClinProTools and a pattern recognition genetic
      algorithm (GA). RESULTS: In the working mass range of 800 - 10 000 Da, 99
      distinctive peaks were resolved in lung adCA versus BLDs, while 101 peaks were
      resolved in lung adCA versus healthy persons. The profile gained by GA that could
      distinguish adCA from BLDs was comprised of 4053.88, 4209.57 and 3883.33 Da with
      sensitivity of 80%, specificity of 93%, while that could separate adCA from
      healthy control was comprised of 2951.83 Da and 4209.73 Da with sensitivity of
      94%, specificity of 95%. The sensitivity provided by carcinoembryonic antigen
      (CEA) in this experiment was significantly lower than our discriminatory profiles
      (P < 0.005). We further identified a eukaryotic peptide chain release factor GTP
      binding subunit (eRF3b) (4209 Da) and a complement C3f (1865 Da) that may serve
      as candidate biomarkers for lung adCA. CONCLUSION: Magnetic beads based MALDI-TOF
      MS technology can rapidly and effectively screen distinctive
      proteins/polypeptides from sera of lung adCA patients and controls, which has
      potential value for establishing a new diagnostic method for lung adCA.

PMID- 20137573
TI  - Oxidative stress and peripheral skeletal muscle dysfunction in rats with
      emphysema.
AB  - BACKGROUND: Peripheral skeletal muscle dysfunction in patients with chronic
      obstructive pulmonary disease (COPD) may be due to the disease per se or as a
      result of concomitant confounding factors. Although the mechanistic basis for
      this functional impairment is uncertain, oxidative stress may play a role. The
      purpose of this study was to investigate whether local oxidative stress is
      associated with the reduced peripheral skeletal muscle performance in rats with
      emphysema. METHODS: In situ mechanical properties of gastrocnemius were measured
      in Sprague-Dawley rats 5 months after intratracheal instillation of either
      elastase (EMP, n = 10) or normal saline (CON, n = 10). Lipofuscin inclusions,
      myocyte apoptosis and antioxidant enzyme activities were examined in the
      gastrocnemius muscle. RESULTS: Lipofuscin inclusions were significantly higher in
      the gastrocnemius muscle of EMP compared with CON (3.2 + or - 0.4 vs. 1.7 + or -
      0.4, P < 0.01). The activities of antioxidant enzymes were significantly
      increased in muscle homogenates of EMP as compared to CON. No significant
      differences were found in myocyte apoptosis between EMP and CON (1.2 + or - 0.9
      vs. 1.0 + or - 0.8, P > 0.05). EMP decreased the fatigue endurance of
      gastrocnemius muscle (half-time to fatigue recovery: (150.0 + or - 55.4) seconds
      vs. (55.2 + or - 29.3) seconds, P < 0.01) and had no effect on maximal tetanic
      force ((467.4 + or - 36.6) g vs. (493.2 + or - 30.5) g, P > 0.05). A
      significantly positive correlation was found between the level of lipofuscin
      inclusions and the half-time to fatigue recovery of gastrocnemius muscle in EMP
      (r = 0.664, P < 0.05). CONCLUSION: Local oxidative stress may have important
      functional consequences for peripheral skeletal muscle in rats with EMP.

PMID- 20137574
TI  - Long-term results of endovascular therapy for proximal subclavian arterial
      obstructive lesions.
AB  - BACKGROUND: Endovascular therapy is a treatment option for localized occlusion of
      the subclavian artery. In this report the long-term experience with 59 patients
      is presented. METHODS: Between June 1998 and September 2008, we used endovascular
      therapy to treat 61 subclavian arterial obstructive lesions in 59 patients (46
      males and 13 females, 34 - 82 years of age with a mean age (61.9 + or - 11.0)
      years). Twenty patients (34%) had clinical symptoms due to vertebrobasilar
      insufficiency, 26 (44%) had disabling arm ischemia, and 13 (22%) had both
      symptoms. We performed all procedures under local anesthesia. The approaches were
      from the femoral artery (n = 47), brachial artery (n = 1, involving bilateral
      subclavian disease) or both (n = 11). Sixty stents were implanted. All patients
      were followed-up at 1, 3, 6, and 12 months post-procedure, and annually
      thereafter. RESULTS: We achieved technical success in 58 (95.1%) arteries, all of
      which were stented. There were three technical failures; two were due to the
      inability to cross over an occlusion, necessitating the switch to an axillo
      axillary bypass, and the third was due to shock after digital subtraction
      angiography and prior to stenting. Arterial stenosis pre- and post-stenting was
      (83.6 + or - 10.8)% and (2.5 + or - 12.5)% (P < 0.01). Clinical success was
      achieved in 55 of the 59 patients (93.4%). Of the four clinical failures, three
      were technical and the remaining patient had a stent thrombosis. Systolic blood
      pressure difference between the two brachial arteries was (44.7 + or - 18.5) vs.
      (2.2 + or - 3.9) mmHg (P < 0.01). Primary patency was 98% at 12 months, 93% at 24
      months, and 82% at 5 years. Five patients were lost to follow-up by 12 months
      post-stenting. Significant recurrent obstruction developed in five patients with
      resumption of clinical symptoms. The overall survival rate was 98.2% at 12
      months, 89.5% at 24 months, and 84.5% at 5 years. CONCLUSIONS: Endovascular
      therapy for proximal subclavian arterial obstructive lesions is effective and
      successful. This minimally invasive treatment may be the first choice of
      treatment for proximal subclavical arterial obstructive lesions.

PMID- 20137575
TI  - Altered CD28 and CD95 mRNA expression in peripheral blood mononuclear cells from
      elderly patients with primary non-small cell lung cancer.
AB  - BACKGROUND: The expression of the co-stimulatory molecule CD28 and death receptor
      CD95 on T cells, which change with age, are considered as important immunological
      parameters of immunosenescence. It is well established that CD28 and CD95 are
      associated with tumorgenesis and tumor progression, but the relationship between
      the age-related changes of these two immunological markers and cancer in the
      elderly is largely unknown. METHODS: The levels of CD28 and CD95 mRNA in
      peripheral blood mononuclear cells (PBMCs) from sixty-three elderly patients
      (aged > or = 60 years) with primary non-small cell lung cancer (NSCLC) were
      analyzed by real-time fluorescence-based quantitative polymerase chain reaction
      (FQ-PCR). In addition, twenty young patients (aged < 60 years) with NSCLC, thirty
      elderly healthy donors and thirty young healthy donors were enrolled as controls.
      RESULTS: CD28 mRNA levels were significantly lower and CD95 mRNA levels were
      significantly higher in elderly patients with NSCLC than in the other groups.
      Similar results were found in elderly healthy donors comparing with young healthy
      donors. By Logistic regression analysis an increased risk of NSCLC was markedly
      associated with aging, down-regulation of CD28 mRNA and up-regulation of CD95
      mRNA, and CD28 mRNA had an obvious negative correlation with the CD95 mRNA. In
      addition, the mRNA levels of CD28 and CD95 in the peripheral blood of the elderly
      patients was closely associated with the tumor node metastasis (TNM) stages,
      grade of cell differentiation and lymph node metastasis status, but not related
      to pathological types. CONCLUSIONS: The results suggest a close relationship
      between T cell senescence and NSCLC tumour progress in the elderly, and that up
      regulation of CD28 mRNA or down-regulation of CD95 mRNA in peripheral blood T
      cells may play an important role in inhibiting oncogenesis and development of
      primary NSCLC in the elderly.

PMID- 20137576
TI  - Twelve cases of the pectoralis major muscle tendon rupture with surgical
      treatment-an average of 6.7-year follow-up.
AB  - BACKGROUND: Pectoralis major tendon rupture is a relatively rare injury leading
      to both functional and cosmetic deficiency. The peak torque of the pectoralis
      major is significantly decreased after conservational treatment of a total
      rupture. We suppose that surgical intervention is better choice. METHODS: We
      retrospectively evaluated 12 patients who were diagnosed with distal pectoralis
      major muscle rupture and underwent operation in our institute from 1993 to 2007.
      All patients were male with a mean age of 32 (19 - 54) years. In 4 patients,
      tendon reconstruction was accomplished by fixing the tendon to the humerus using
      sutures passed through predrilled humeral bone tunnels. In 8 patients, tendon
      reconstruction was accomplished by directly suturing the muscle to the tendon.
      All patients followed an accelerated rehabilitation protocol. Treatment results
      were evaluated according to the following criteria: (1) visual analogue pain
      scale, (2) isokinetic strength measurements, (3) range of motion of shoulder
      joint, (4) cosmetic result, and (5) postoperative sports activity performance. In
      this study, we aimed to describe our surgical technique of reconstruction of the
      rupture of pectoralis major muscle and to summarize the clinical results of the
      operative treatment. RESULTS: At the final follow-up examination (6.5 years
      postoperatively), only nine patients were available for evaluation. Three of them
      had excellent results, and five had good results, while one had poor results.
      Eight of the patients were able to return to their preinjury level of sporting
      activity. In summary, 89% of the patients achieved excellent or good results.
      CONCLUSION: Surgical treatment by anatomic tendon repair and accelerated
      rehabilitation can make recovery of strength and function of the pectoralis major
      muscle.

PMID- 20137577
TI  - Grass height and transmission ecology of Echinococcus multilocularis in Tibetan
      communities, China.
AB  - BACKGROUND: Alveolar echinococcosis is a major zoonosis of public health
      significance in western China. Overgrazing was recently assumed as a potential
      risk factor for transmission of alveolar echinococcosis. The research was
      designed to further test the overgrazing hypothesis by investigating how
      overgrazing influenced the burrow density of intermediate host small mammals and
      how the burrow density of small mammals was associated with dog Echinococcus
      multilocularis infection. METHODS: The study sites were chosen by previous
      studies which found areas where the alveolar echinococcosis was prevalent. The
      data, including grass height, burrow density of intermediate host small mammals,
      dog and fox fecal samples as well as Global Positioning System (GPS) position,
      were collected from field investigations in Shiqu County, Sichuan Province,
      China. The fecal samples were analyzed using copro-PCR. The worms, teeth, bones
      and hairs in the fecal samples were visually examined. Single factor and
      multifactor analyses tools including chi square and generalized linear models
      were applied to these data. RESULTS: By using grass height as a proxy of grazing
      pressure in the homogenous pasture, this study found that taller grass in the
      pasture led to lower small mammals' burrow density (chi(2) = 4.670, P = 0.031,
      coefficient = -1.570). The Echinococcus multilocularis worm burden in dogs was
      statistically significantly related to the maximum density of the intermediate
      host Ochotona spp. (chi(2) = 5.250, P = 0.022, coefficient = 0.028). The
      prevalence in owned dogs was positively correlated to the number of stray dogs
      seen within a 200 meter radius (Wald chi(2) = 8.375, P = 0.004, odds ratio =
      1.198). CONCLUSIONS: Our findings support the hypothesis that overgrazing
      promotes transmission of alveolar echinococcosis and confirm the role of stray
      dogs in the transmission of alveolar echinococcosis.

PMID- 20137578
TI  - Effect of fusion protein TAT and heme oxygenase-1 on liver sinusoidal endothelial
      cells apoptosis during preservation injury.
AB  - BACKGROUND: Proteins or peptides can be directly transferred into cells when
      covalently linked to protein transduction domains (PTDs). TAT is one of the most
      widely studied PTDs. The effect of fusion protein TAT and heme oxygenase-1 (HO-1)
      on liver sinusoidal endothelial cells (SECs) apoptosis during cold storage is
      unknown. The present study aimed to determine whether fusion protein TAT-HO-1
      would transduce efficiently into liver during cold storage, and, if so, to
      determine whether TAT-HO-1 would attenuate SECs apoptosis during preservation
      injury in rat. METHODS: Livers of Sprague-Dawley rats were harvested and randomly
      assigned to group 1 (HTK solution) and group 2 (HTK solution containing TAT-HO-1
      fusion protein) according to the type of the preservation solution. The
      transduction efficiency of TAT-HO-1 was examined and the impairment of SECs was
      assessed during the period of cold storage followed by 1 hour of reperfusion.
      RESULTS: TAT-HO-1 can transduce efficiently into liver during cold storage. A
      significantly lower apoptotic index of SECs was observed in group 2, at 6, 12 and
      18 hours of cold storage after 1 hour reperfusion, when compared with group 1.
      TAT-HO-1 reduced HA and ET levels in liver at each time point. Both Bcl-2 and Bax
      protein were expressed in hepatocytes and SECs at the periphery of the sinusoidal
      space. Moreover, higher Bcl-2 expression and lower Bax expression were observed
      in group 2. CONCLUSIONS: TAT-HO-1 can transduce efficiently into rat livers and
      shows a protective effect on SECs by attenuating apoptosis during cold
      ischemia/reperfusion injury. Protein transduction will be a novel therapeutic
      strategy to reduce the risk of preservation injury in liver transplantation.

PMID- 20137579
TI  - The effect of oxidative stress in myocardial cell injury in mice exposed to
      chronic intermittent hypoxia.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is an important risk factor
      for cardiovascular diseases. Chronic intermittent hypoxia (CIH) is considered to
      be one of the most important causes of cardiovascular diseases in OSA patients.
      This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion
      injury, which initiates oxidative stress. In this study, we observed cardiocytes
      injury induced by CIH and the effect of N-acetylcysteine (NAC). METHODS: Thirty
      ICR mice were randomly assigned to 3 groups: control, CIH and NAC (CIH + NAC)
      groups. Malondialdehyde (MDA) and superoxide dismutase (SOD) of cardiocyte
      homogenates were measured. Serum lipids were measured by an instrument method.
      Serum cardiac troponin I (cTnI) was detected by enzyme-linked immunosorbent
      assays (ELISA). Myocardium pathological sections were observed. RESULTS: (1) The
      SOD activity and MDA concentration of cardiocyte homogenates in the CIH group
      were significantly higher than in other groups (P < 0.005). The MDA concentration
      of the NAC group was lower than that of the control group (P < 0.01). (2) The
      serum cTnI concentration of the CIH and NAC groups was significantly higher than
      that of the control group (P < 0.01). (3) Serum triglyceride levels in the NAC
      group were lower than in the other groups (P < 0.01), while there were no
      significant differences in low density lipoprotein and high density lipoprotein
      among the three groups. (4) The degeneration of myocardium, transverse striation
      blurred, and fabric effusion were observed in tissue sections in the CIH and NAC
      groups. However, normal tissue was found in the control group. CONCLUSION: The
      oxidative stress induced by CIH can injure cardiocytes and the injury effect can
      be partially inhibited by NAC.

PMID- 20137580
TI  - Effects of mixture of lidocaine and ropivacaine at different concentrations on
      the central nervous system and cardiovascular toxicity in rats.
AB  - BACKGROUND: Lidocaine and ropivacaine are often combined in clinical practice to
      obtain a rapid onset and a prolonged duration of action. However, the systemic
      toxicity of their mixture at different concentrations is unclear. This study
      aimed to compare the systemic toxicity of the mixture of ropivacaine and
      lidocaine at different concentrations when administered intravenously in rats.
      METHODS: Forty-eight male Wistar rats were randomly divided into 4 groups (n = 12
      each): 0.5% ropivacaine (group I); 1.0% ropivacaine and 1.0% lidocaine mixture
      (group II); 1.0% ropivacaine and 2.0% lidocaine mixture (group III); and 1.0%
      lidocaine (group IV). Local anesthetics were infused at a constant rate until
      cardiac arrest. Electrocardiogram, electroencephalogram and arterial blood
      pressure were continuously monitored. The onset of toxic manifestations (seizure,
      dysrhythmia, and cardiac arrest) was recorded, and then the doses of local
      anesthetics were calculated. Arterial blood samples were drawn for the
      determination of local anesthetics concentrations by high-performance liquid
      chromatography. RESULTS: The onset of dysrhythmia was later significantly in
      group IV than in group I, group II, and group III (P < 0.01), but there was no
      significant difference in these groups (P > 0.05). The onset of seizure, cardiac
      arrest in group I ((9.2 + or - 1.0) min, (37.0 + or - 3.0) min) was similar to
      that in group II ((9.1 + or - 0.9) min, (35.0 + or - 4.0) min) (P > 0.05), but
      both were later in group III ((7.5 + or - 0.7) min, (28.0 + or - 3.0) min) (P <
      0.05). The onset of each toxic manifestation was significantly later in group IV
      than in group I (P < 0.01). The plasma concentrations of the lidocaine-alone
      group at the onset of dysrhythmia (DYS), cardiac arrest (CA) ((41.2 + or - 6.8)
      min, (59.0 + or - 9.0) min) were higher than those of the ropivacaine alone group
      ((20.5 + or - 3.8) min, (38.0 + or - 8.0) min) (P < 0.05). The plasma
      concentrations of ropivacaine inducing toxic manifestation were not significantly
      different among groups I, II, and III (P > 0.05). CONCLUSIONS: The systemic
      toxicity of the mixture of 1.0% ropivacaine and 2.0% lidocaine is the greatest
      while that of 1.0% lidocaine is the least. However, the systemic toxicity of the
      mixture of 1.0% ropivacaine and 1.0% lidocaine is similar to that of 0.5%
      ropivacaine alone.

PMID- 20137581
TI  - Effect on cochlea function of guinea pig after controlled release recombinant
      human bone morphogenetic protein 2.
AB  - BACKGROUND: The recombinant human bone morphogenetic protein 2 (rhBMP-2) has been
      used to induce osteogenesis in animals' middle ear and this technique is possible
      to be used to reconstruct the defects of ossicles. The side effects of the rhBMP
      2 in middle ear should be observed before using in clinic. Thus we prepared the
      controlled release rhBMP-2 and implanted it into the acoustic bulla of guinea
      pigs. The effect on the cochlea was observed. METHODS: We prepared the acellular
      cancellous bone, accompanied with rhBMP-2. The material accompanied with rhBMP-2
      was implanted into one acoustic bulla of the animal and the opposite side of the
      acoustic bulla was implanted with acellular cancellous bone without rhBMP-2.
      Totally 20 guinea pigs were undergone this procedure. After the operation, the
      auditory brainstem response (ABR) of the animals was tested according to the time
      sequence. Three months after the operation, the animals were sacrificed. The
      osteogenesis induced by rhBMP-2, the acoustic bulla and cochlea affected by rhBMP
      2 were observed. The structures of hair cells were observed after silver nitrate
      staining. RESULTS: The animals were recovered soon after surgery. The hearing
      thresholds of the animals were declined slightly just after the surgery and come
      back completely after 3 months. Also, the bulla and cochlea were normal in shape.
      The osteogenesis occurred in the pore of the acellular cancellous bone with rhBMP
      2. There was not any abnormal hyperplasia of bone in the bulla and cochlea. The
      articulation between the stapes and oval window was not merged. The shapes of the
      hair cells were normal and there was no obvious deletion of the hair cells
      compared with control group. CONCLUSIONS: The controlled release rhBMP-2
      transplanted into the middle ear could induce osteogenesis in the bulla of the
      animals. It did not affect the shape of the bulla and the hearing threshold of
      the animal, and did not induce the abnormal hyperplasia of bone in the bulla and
      might be used to reconstruct the defects of ossicles.

PMID- 20137582
TI  - Sleep apnea hypopnea syndrome and liver injury.
AB  - OBJECTIVE: A general review was made of studies involving: (1) the relationship
      between sleep apnea hypopnea syndrome/sleep apnea style intermittent hypoxia and
      liver injury and (2) the mechanism that causes the liver injury. DATA SOURCES:
      The data used in this review were mainly from Medline and PubMed published in
      English from 1993 to February 2009. The search term was "sleep apnea hypopnea
      syndrome". STUDY SELECTION: (1) Clinical and laboratory evidence that sleep apnea
      hypopnea syndrome and sleep apnea style intermittent hypoxia leads to liver
      injury; (2) the mechanism that causes the liver injury. RESULTS: The effect of
      sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia on the
      liver function is characterized by serum aminotransferase elevation. The liver
      histological injury includes hepatic steatosis, hepatocyte ballooning, lobular
      inflammation, lobular necrosis, and liver fibrosis. Sleep apnea hypopnea syndrome
      and sleep apnea style intermittent hypoxia can cause insulin resistance and
      oxidative stress. CONCLUSIONS: Sleep apnea hypopnea syndrome and sleep apnea
      style intermittent hypoxia can lead to chronic liver injury, which, in most
      cases, is shown as nonalcoholic fatty liver disease. Insulin resistance and
      oxidative stress caused by sleep apnea hypopnea syndrome and sleep apnea style
      intermittent hypoxia play an important role in the mechanism of chronic liver
      disease development.

PMID- 20137583
TI  - Cyclic adenosine monophosphate signal pathway in targeted therapy of lymphoma.
AB  - OBJECTIVE: To review the role of cyclic adenosine monophosphate (cAMP) signal
      pathway in the pathogenesis of lymphoma and explore a potential lymphoma therapy
      targeted on this signaling pathway. DATA SOURCES: The data cited in this review
      were mainly obtained from the articles listed in Medline and PubMed, published
      from January 1995 to June 2009. The search terms were "cAMP" and "lymphoma".
      STUDY SELECTION: Articles regarding the role of the cAMP pathway in apoptosis of
      lymphoma and associated cells and its potential role in targeted therapy of
      lymphoma. RESULTS: In the transformation of lymphocytic malignancies, several
      signal pathways are involved. Among of them, the cAMP pathway has attracted
      increasing attention because of its apoptosis-inducing role in several lymphoma
      cells. cAMP pathway impairment is found to influence the prognosis of lymphoma.
      Targeted therapy to the cAMP pathway seems to be a new direction for lymphoma
      treatment, aiming at restoring the cAMP function. CONCLUSIONS: cAMP signal
      pathway has different effects on various lymphoma cells. cAMP analogues and
      phosphodiesterase 4B (PDE4B) inhibitors have potential clinical significance.
      However, many challenges remain in understanding the various roles of such
      agents.

PMID- 20137584
TI  - Radiological features of lung changes caused by avian influenza subtype A H5N1
      virus: report of two severe adult cases with regular follow-up.

PMID- 20137585
TI  - Application of fetoscopy in the management of monochorionic multiple pregnancies.

PMID- 20137586
TI  - Homoharringtonine in combination with cytarabine and aclarubicin as induction
      therapy improves remission and survival of patients with higher risk
      myelodysplastic syndromes.

PMID- 20137587
TI  - Choroidal malignant melanoma in patients with oculodermal melanocytosis: report
      of three cases.

PMID- 20137588
TI  - Coronary arteriovenous fistula with giant aneurysm formation treated with
      percutaneous intervention.

PMID- 20137589
TI  - Sturge-Weber syndrome: a case report and review of literatures.

PMID- 20137590
TI  - Giant leiomyosarcoma of the pelvis: diagnosis and surgical management.

PMID- 20137592
TI  - [Vascular endothelial injury: a key event in occurrence and development of sepsis
      relationship of treatment and life-saving in critical medicine].

PMID- 20137593
TI  - [Effect of lung stress index upon titration of positive end-expiratory pressure
      at post-recruitment in patients with acute respiratory distress syndrome].
AB  - OBJECTIVE: To investigate the relationship of stress index and positive end
      expiratory pressure (PEEP) in patients with acute respiratory distress syndrome
      (ARDS) and to determine the relationship of stress index, lung recruitment,
      oxygenation and respiration mechanics. METHODS: Fourteen ARDS patients were
      enrolled. During volume control ventilation with constant inspiratory flow, the
      pressure-time (P-t) curve was fitted to a power equation: P = a x time(b) + c,
      where coefficient b (stress index) describes the shape of curve: b = 1, straight
      curve; b < 1, progressive increase in slope; and b > 1, progressive decrease in
      slope. Positive end-expiratory pressure (PEEP) was set to obtain b value between
      0.9 and 1.1 after application of a recruiting maneuver (RM). PEEP was changed to
      obtain 0.6 < b < 0.8 and 1.1 < b < 1.3. The sequence of experimental conditions
      was random. Recruited volume (RV) was measured by static pressure-volume curve
      method. Hemodynamics, pulmonary mechanics and gas exchange were observed
      simultaneously. RESULTS: PEEP at b < 1, b = 1 and b > 1 were (8.3 +/- 1.5) cm
      H2O, (15.0 +/- 1.9) cm H2O and (18.4 +/- 1.9) cm H2O respectively with a
      significant difference (P < 0.001). At b = 1 and b > 1, the partial arterial
      oxygen tension (PaO2/FiO2) [(350 +/- 113) mm Hg, (338 +/- 124 mm Hg)] were higher
      than that [165 +/- 60) mm Hg] of pre-RM (P < 0.05). the plateau pressure (Pplat)
      at b = 1 [(29 +/- 4) cm H2O] and b > 1 [(33 +/- 7) cm H2O] post-RM were
      significantly higher than that at b < 1 [(22 +/- 4) cm H2O] (P < 0.05); the Pplat
      at b > 1 was higher than that [(25 +/- 16) cm H2O] pre-RM (P < 0.05). Compared
      with the static pulmonary compliance (Cst) at b = 1 [(39 +/- 11) ml/cm H2O], Cst
      at b > 1 [(26 +/- 7) ml/cm H2O] decreased significantly (P < 0.05). The RV at b =
      1 and b > 1 [(402 +/- 204) ml, (588 +/- 269) ml] were significantly higher than
      that at pre-RM and b < 1 [(136 +/- 111) ml, (175 +/- 122) ml] (P < 0.05). At pre
      RM, b < 1, b = 1 and b > 1, HR, mean arterial pressure (MAP) and lactate showed
      no significant difference (P > 0.05). CONCLUSION: Stress index at post-RM can be
      an excellent method of PEEP titration for ARDS patients.

PMID- 20137594
TI  - [Effect of XueBiJing injection upon related proinflammatory factors and blood
      coagulation factors of vascular endothelial cells in severe septic patients].
AB  - OBJECTIVE: To evaluate the effect of Xue Bijing injection in related
      proinflammatory factors and blood coagulation factors of vascular endothelial
      cell in severe septic patients. METHODS: Fifty-two patients were randomly divided
      into Xue Bijing injection treatment group (Group B) and control group (Group A).
      Both groups were treated with routine integration treatment, and additionally,
      patients in Group B received Xue Bijing injection 100 ml intravenous once a day
      for 7 days while those in Group A received an equal quantity of normal saline as
      placebo. The changes of VCAM-1, ICAM-1, NO, AT-III, TM, TPA, VWF and PAI-1 in
      blood serum were tested at Day 0, 3, 7. And the mortality was calculated at Day
      28. RESULTS: The 28-day mortality rate was 32.1% (9/28) in Group B while that of
      Group A was 62.5% (15/24). There was a significant difference between two groups
      (P < 0.05). The concentrations of blood serum VCAM-1 and ICAM-1 were
      significantly lower in Group B than Group A. And the concentrations of blood
      serum NO, AT-III, TM, TPA, VWF and PAI-1 were significantly higher in Group B
      than Group A. CONCLUSION: Xue Bijing injection improves a patient's condition and
      reduces 28-day mortality of severe septic patients. The reason may be that it can
      stabilize vascular endothelial cell to improve serious inflammatory reaction and
      blood coagulation dysfunction.

PMID- 20137595
TI  - [Application of RIFLE criteria for acute renal failure in patients treated with
      continuous renal replacement therapy].
AB  - OBJECTIVE: To determine the optimal timing of treating acute renal failure (ARF)
      patients in intensive care unit (ICU) with RIFLE (risk of renal failure, injury
      to the kidney, failure of kidney function, loss of kidney function and end-stage
      renal failure) classification using continuous renal replacement therapy (CRRT).
      And to evaluate the association between mortality and RIFLE classification in the
      same patients. METHODS: Clinical data were collected from 103 ARF patients in ICU
      from 2000 to 2007. RESULTS: The 30-days hospital mortality rate was 45.6%. The 30
      days' hospital mortality rates of RIFLE-R, RIFLE-I and RIFLE-F were 25.0%, 20.0%
      and 57.3% respectively. CONCLUSION: Survival rate of ARF patients can be
      manifestly elevated if CRRT is performed before RIFLE-F. The patients in RIFLE-F
      category have a significantly higher mortality than RIFLE-R and -I patients. The
      RIFLE criteria is fit for ARF classification system.

PMID- 20137596
TI  - [Effects of preemptive analgesia with flurbiprofen on the blood sugar and
      interleukin-6 of patients after radical excision of breast cancer].
AB  - OBJECTIVE: To investigate the effects of preemptive analgesia with flurbiprofen
      on the blood sugar and Interleukin-6 of patients after radical excision of breast
      cancer. METHODS: A total of 60 ASA I-II patients scheduled for radical excision
      of breast cancer were randomly assigned to three groups: group A, B and C (n = 20
      each), patients of group A and C received intravenous flurbiprofen 100 mg before
      or at the end of surgery respectively. Blood samples were collected from the
      patients before anaesthesia induction and 1, 6, 24 h after surgery for the
      determination of blood sugar and serum interleukin-6 concentration. Analgesic
      efficacy was assessed after surgery based on visual analog scales (VAS). RESULTS:
      The blood sugar and serum interleukin-6 concentration of the patients in three
      groups at different time points after surgery were significantly higher than
      those before surgery, and increased gradually in group B, and there were very
      significant difference between the time point of 1 h and 24 h after surgery (P <
      0.01), but there were no increasing trend for those of group A and C. The blood
      sugar and serum interleukin-6 concentration of the patient of group A were
      significantly lower than those of group B and C (P < 0.01 or 0.05). The highest
      VAS of group A and C at different time points after surgery were significantly
      lower than that of group B(P < 0.05). CONCLUSION: Preemptive analgesia with
      flurbiprofen 100 mg can effectively suppress the elevation of blood sugar and
      serum interleukin-6 concentration after radical excision of breast cancer, and is
      better than postoperation analgesia.

PMID- 20137597
TI  - [Microsurgical anatomy and quantitative assessment of suboccipital median
      transcerebellomedullary fissure keyhole approach].
AB  - OBJECTIVE: To assess the suboccipital median transcerebellomedullary fissure
      keyhole approach in a cadaver model by using a neuronavigation system and explore
      its feasibility and operative indications. METHODS: Six 10% formaldehyde-fixed
      adult cadaveric head and neck specimens injected with colored latex were chosen
      for the study. First the suboccipital median transcerebellomedullary fissure
      keyhole approach was performed and the anatomical structures were observed under
      operative microscope. The exposed floor area of the fourth ventricle and the
      vertical and transverse angles at the point where the line between the lateral
      apertures crossing the median sulcus, vertical angle at the apertures of midbrain
      aqueduct and the obex were measured with the aid of a frameless stereotactic
      navigation device. Parameters were compared with those when C1 posterior arch was
      removed, and also with those under conventional approach with or without C1 arch.
      RESULTS: By means of adjusting specimen positions and the angle of operative
      microscope, as tela choroidea and inferior medullary velum were dissected
      gradually, the structures of floor, lateral recesses and lateral apertures of the
      fourth ventrical, vermian and aperture of midbrain aqueduct were exposed. There
      were no significant difference in the exposed floor area of the fourth ventricle
      between the keyhole approach and conventional approach (P = 0.06), and the C1
      arch removal can't increase the exposed area (P = 0.84). The conventional
      approach have wider angles than the keyhole approach (P < 0.01), and the C1 arch
      removal increased the vertical angle (P < 0.05), but not the horizontal angle (P
      > 0.05). CONCLUSION: The suboccipital median transcerebellomedullary fissure
      keyhole approach can expose similar anatomic architectures as that of the
      conventional approach. Thus it can be used to remove the tumors located in the
      fourth ventricle, dorsum of pons and medullary oblongata and cerebellar vermis.

PMID- 20137598
TI  - [Association between metabolic syndrome and prognosis in acute ischemic non
      embolic stroke].
AB  - OBJECTIVE: To investigate the association between metabolic syndrome (MS) and
      stroke severity in at-admission patients with acute ischemic non-embolic stroke
      and to study the impact of MS upon prognosis; and to assess the relative
      influence of each of five components of MS upon the risk of stroke severity.
      METHODS: The consecutive cases of ischemic stroke were prospectively registered
      in neurology wards from March 2006 to March 2008. Only those patients with an
      onset of stroke within 24 hours were included. The outcomes were followed up at
      the end of 3 months after stroke onset. MS was defined according to the Chinese
      Diabetes Society criteria. Logistic regression was used to estimate the
      correlation of MS and prognosis. RESULTS: A total of 342 patients with acute
      ischemic non-embolic stroke within 24 hours from onset were included. Eighty six
      patients (50 males, 36 females) had MS. The prevalence of individual components
      of MS was significantly higher in patients with MS as compared with those
      without. The delay from onset of symptoms to hospital admission and MS were
      associated with severe stroke in multiple logistic regression model (RR = 2.45,
      95%CI, 1.14-5.27; RR = 1.85, 95%CI, 1.06-6.25 respectively). Analysis of the
      association between the development risk of sever stroke showed that
      hyperglycemia and low triglyceride level had associations with severe stroke (RR
      = 3.02, 95%CI, 1.75-8.59; RR = 0.85, 95%CI, 0.24-0.96 respectively). MS was not
      an independent predictor for case fatality and poor outcome 3 months after stroke
      onset (all P > 0.05). CONCLUSION: Not an independent predictor for mortality and
      poor outcome at 3 months after stroke onset, MS is an independent predictor for
      the severity of stroke and there is a higher development risk of severe stroke.
      Among MS components, hyperglycemia and low triglyceride level are correlated with
      the development risk of severe stroke. This finding has important clinical
      implication and confirms the importance of glycemic control during acute phase of
      ischemic stroke.

PMID- 20137599
TI  - [Prophylaxis and management of early acute renal failure after orthotopic liver
      transplantation].
AB  - OBJECTIVE: To summarize the experiences of prophylaxis and management of early
      period acute renal failure (ARF) after orthotopic liver transplantation (OLTx).
      METHODS: The clinical data of 516 patients from January 2004 to December 2006 at
      our hospital undergoing allograft orthotopic liver transplantation, 418 males and
      98 females, aged 43 (8-76) years old, were collected to analyze the incidence of
      early ARF. RESULTS: Of these patients, 106 (20.5%)experienced early ARF,
      including 21 mild, 40 moderate and 45 severe cases. The integrated control
      treatment including retrieving prerenal factors, adjusting immunosuppressive
      schedule, drug therapy and blood purification were taken to cure ARF and 21
      patients of severe ARF needed continuous renal replacement therapy (CRRT). Of 106
      patients, 37 (34.9%) died within 1 month post-OLT. The one month post-OLT
      survival rate of patients with MELD (model for end-stage liver disease) score
      less than 20 fared better than those whose MELD score between 20 to 30 and MELD
      score over 30. CONCLUSION: The prophylaxis and management of early post-OLT ARF
      is a systemic procedure from preoperative assessment to postoperative management.
      The significant steps of preventing and curing ARF within perioperative procedure
      of OLTx include preoperative evaluation of patient renal function, various intra
      operative measures for protecting renal function, reducing renal function
      impairment due to drug toxicity after OLT and CRRT treatment if needed.

PMID- 20137600
TI  - [Meta-analysis of unicompartmental knee arthroplasty versus high tibial osteotomy
      in the treatment of unicompartmental knee osteoarthritis].
AB  - OBJECTIVE: To assess the efficacy of UKA versus HTO in the treatment of
      unicompartmental knee osteoarthritis. METHODS: Comparative studies of UKA and HTO
      were retrieved from the domestic and foreign literatures and included for a meta
      analysis. RESULTS: Seven eligible randomized controlled trials included 196 UKAs
      and 219 HTOs. The result of Meta-analysis indicated that the ratio for an
      excellent outcome was higher in UKA than HTO. The combined OR was 2.43, 95%CI
      (1.46, 4.05) (P = 0.0006). The risks of revision and complications were lower in
      UKA than HTO. The combined OR was 0.47 and 0.24 and 95%CI (0.23, 0.97), (0.10,
      0.56). CONCLUSION: UKA reduces the risk of postoperative revision and
      complications and provides excellent outcomes.

PMID- 20137601
TI  - [Characteristics and related factors of illness perception in Chinese cancer
      patients].
AB  - OBJECTIVE: To investigate the illness perception of cancer patients as well as
      the difference of illness perception between cancer patients and diabetics so as
      to help them to derive meaning from illness experiences and facilitate
      posttraumatic growth. METHODS: A sample of 210 Chinese cancer patients and 71
      diabetics was recruited from the same hospital and CIPQ-R completed. RESULTS:
      Cancer patients had higher consequences [F (1, 275) = 23.32, P < 0.001(2) = 0.08]
      and emotional representation [F (1, 275) = 25.95, P < 0.001(2) = 0.09]; as well
      as less perceived controls over illness as compared with diabetics. Among the
      cancer patients, those with a better understanding about the meaning of illness
      tended to report more positive changes. CONCLUSION: Illness perception is one of
      the important cognitive components affecting posttraumatic growth of cancer
      patients. Helping patients to derive meaning from their illness experiences
      facilitates the posttraumatic growth after cancer diagnosis.

PMID- 20137602
TI  - [Clinical experience of surgical treatment on hypertrophic obstructive
      cardiomyopathy].
AB  - OBJECTIVE: To evaluate the surgical outcome of hypertrophic obstructive
      cardiomyopathy (HOCM). METHODS: From October 1996 to December 2007, 54 HOCM
      patients underwent surgical treatment. There were 37 males and 17 females ranging
      from 6 to 68 years old (36 +/- 16) with body weight 27-83 (60 +/- 14) kg.
      Operation was performed under general anesthesia and cardiopulmonary bypass (CPB)
      with the moderate systemic temperature and low volume blood flow. The concomitant
      operations included coronary artery bypass grafting in 5 cases, mitral valve
      plasty in 5 cases, mitral valve replacement in 9 cases, tricuspid valve plasty in
      2 cases, aortic valve replacement in 4 cases and closure of patent ductus
      arteriosus in 2 cases. Preoperative and postoperative left ventricular (LV), left
      ventricular outflow tract (LVOT), left atrium (LA), mitral valve function and
      value of LVEF were evaluated by transesophageal echocardiograph examination.
      RESULTS: The time of CPB and aortic occlusion were 40 to 290 minutes (107 +/- 52)
      and 27 to 195 min (70 +/- 36 min) respectively. The endotracheal intubation
      durations were 5 to 21 hours (14 +/- 15) and ICU duration 11 to 183 hours (45 +/-
      34). Comparing with the pre-operative echocardiographic parameters, the size of
      left atrium (42 +/- 8 vs 35 +/- 7), pressure gradients through LVOT (106 +/- 44
      mm Hg vs 24 +/- 19 mm Hg), the thickness of septum (27 +/- 6 mm vs 19 +/- 5 mm)
      and the value of EF (70 +/- 10 vs 61 +/- 9) obviously decreased postoperatively
      (P < 0.05). The surviving patients had either no mitral valve regurgitation or
      only mild mitral valve regurgitation. Four (7.4%) patients died during the
      perioperative period. The cause of death included severe low cardiac output,
      heart failure, severe ventricular arrhythmias and severe acute renal failure.
      There were 4 patients with a complete AV block postoperatively and 3 were
      implanted permanent pacemakers. The left bundle branch block or left anterior
      hemiblock were found in 26 cases, intraventricular conduction defect in 6 cases
      and type I AV block in 4 cases. All surviving patients were in NYHA functional
      class I/II during the follow-up of 1 month to 10 years. CONCLUSION: Surgical
      outcome for HOCM patients is satisfactory. Most HOCM patients achieve such a
      satisfactory relief of LV outflow tract obstruction as to lead a better life.

PMID- 20137603
TI  - [Clinical significance on atypical cervical glandular cytology].
AB  - OBJECTIVE: To determine the pathological features and clinical implications of
      atypical glandular cells of undetermined significance (AGC) in cervical
      cytological results. METHODS: All 87 cases of cervical cytological examinations
      with AGC were identified by a computerized database in our patient population.
      The authors analyzed the cervical histopathological results by colposcopic
      biopsy, dilatation and curettage (D&C), cervical loop electrosurgical excision
      procedure (LEEP)and follow-ups. RESULTS: (1) Thirty-five cases (40.23%) had
      cervical and endometrial neoplasic findings: ten glandular lesions (11.49%) and
      squamous lesion was present in 25 patients (28.74%). (2) Among 61 patients with
      Pap smears subclassified as "AGC-not otherwise specified", there were 18
      pathological abnormalities. Sixteen patients with AGC as "favor intraepithelial
      neoplasia" were of 9 pathological abnormalities. Ten patients with AGC as
      "adenocarcinoma in situ" or "adenocarcinoma" were of 6 pathological
      abnormalities. (3) 100% of patients with AGC had both of colposcopic and
      cytologic follow-ups: 1 case CIN1, 1 case CIN2 and 1 case CIN3. (4) One of 10
      patients was younger than 35 years old with CGIN1 and the other 9 patient aged
      over 35 years old had a greater diversity of glandular lesions. CONCLUSION: A
      finding of AGC requires both colposcopy and an aggressive workup because of a
      high rate of cancer and precancerous lesions. The onset of disease is age
      related. Women aged over 35 years old has a greater diversity of glandular
      lesions and account for most cases of cervical and endometrial adenocarcinoma.

PMID- 20137604
TI  - [Study of serum thyroid hormone levels changes in perioperation patients accepted
      coronary artery bypass grafts].
AB  - OBJECTIVE: To clarify the change of serum thyroid hormone levels during
      perioperation period of coronary artery bypass grafts (CABG). METHODS: The levels
      of serum thyroid hormones (TT(3), TT(4), FT(3), FT(4), TSH, rT(3)) were measured
      by chemical-luminal and RIA in 62 patients at certain time in perioperation
      period, as well as 30 normal volunteers on a fasting basis. SPSS 10.0 was used
      for statistic analysis. RESULTS: The levels of serum thyroid hormones had no
      significant difference between controls and patients before CABG. At 10 min and
      60 min after giving heparin, serum TT(4), FT(4) levels in patients during
      operation elevated significantly than before (P < 0.01), however, at 2 h after
      operation, serum TT(3), TT(4), FT(3), FT(4), rT(3), TSH levels had no significant
      changes. Serum TT(3), TT(4), FT(3), FT(4), TSH levels at 24 h and 72 h after
      operation were significantly lower in patients than before CABG (P < 0.01).
      Especially at 24 h, serum TT(3), FT(3) levels decreased by 52.7% and 46.6% than
      before respectively, while serum rT(3) levels increased significantly (P < 0.01)
      and serum TT(3), rT(3) levels decreased significantly (P < 0.01). The serum
      TT(4), FT(3), FT(4), TSH levels didn't return to normal at 7 d after operation.
      CONCLUSION: Elevated serum TT(4), FT(4) levels are present in acute period in
      patients accepted CABG. Decreased serum T(3) and FT(3) levels after CABG may
      indicate a bad prediction.

PMID- 20137605
TI  - [Characteristics of patients with primary Sjogren's syndrome and non-Hodgkin's
      lymphoma: analysis of 9 cases].
AB  - OBJECTIVE: To characterize the clinical patterns of expression, laboratory
      serologic parameters and lymphomatous histological characteristics in patients
      with primary Sjogren's syndrome (pSS) who subsequently developed non-Hodgkin's
      lymphoma (NHL). METHODS: The authors analyzed 9 pSS patients (8 females, 1 male)
      who developed NHL. Five patients had received glucocorticoids, four of whom had
      received at least one immunosuppressive drugs (methotrexate, glucosidorum
      tripterygll totorum, cyclophosphamide and imuran). A protocol form was used to
      record the main characteristics of pSS and NHL. RESULTS: Eight patients fulfilled
      the American-European Consensus Criteria (AECC). The main SS manifestations were
      painless parotid enlargement (n = 7), six of whom were unilateral; the main
      immunologic features were positive rheumatoid factor (RF) in all examined
      patients and hyperimmunoglobulinemia (n = 7). The main manifestations of NHL were
      splenomegaly (n = 7) and lymphadenopathy (n = 5). The main histological subtypes
      were mucosa-associated lymphoid tissue (MALT) lymphoma (n = 4) and diffuse large
      B cell lymphoma (n = 2). None of the patients with MALT lymphoma had a nodal
      primary location. Eight patients had an extranodal primary location, most
      frequently in salivary gland (n = 4) and lung (n = 4). CONCLUSION: Patients with
      pSS and NHL are clinically characterized by a high frequency of painless
      unilateral parotid enlargement, splenomegaly, lymphadenopathy, an immunologic
      pattern dominated by the presence of high-titer RF and hyperimmunoglobulinemia, a
      predominance of MALT lymphomas and an elevated frequency of primary extranodal
      involvement.

PMID- 20137606
TI  - [Effects of N-acetylcysteine upon methylglyoxal-induced damage in hippocampal
      neuronal cells].
AB  - OBJECTIVE: To explore the effects of N-acetylcysteine (NAC) upon the
      methylglyoxal (MG)-induced injury of hippocampal neuronal cells. METHODS: Primary
      cultures of 1-day-old SD rat hippocampal neuron were exposed to MG and/or NAC for
      24 h respectively. Apoptosis was quantified by flow cytometer using annexin V
      FITC and propidium iodide (PI) staining. The level of intracellular reactive
      oxygen species (ROS) was measured by an oxidant-sensitive dye 2,7
      dichlorofluorescin diacetate (DCFH). The protein and mRNA levels of BDNF and TrkB
      were assayed with Western blot and real-time reverse-transcription polymerase
      chain reaction (RT-PCR) respectively. RESULTS: After a 24 h cell incubation with
      100 micromol/L MG, the ratio of apoptotic cells in MG group (8.80 +/- 0.31)%
      significantly increased versus the control group (1.60 +/- 0.15)% and MG+NAC
      group (4.83 +/- 0.31)% respectively. The level of intracellular oxidation of MG
      group (10 229 +/- 946) also significantly increased versus the NAC group (2118 +/
      320), control group (4265 +/- 82), MG + NAC group (3886 +/- 415) and pretreated
      NAC + MG group (2997 +/- 606). MG increased the cellular levels of BDNF but
      decreased the TrkB mRNA and protein expression significantly. However, NAC
      significantly decreased the BDNF and increased the TrkB mRNA and protein
      expression in rat hippocampal neuron after MG induction. All these differences
      were considered statistically significant. CONCLUSION: MG-induced neurotoxicity
      in hippocampal neurons is mediated by oxidative stress and it can impair the
      BDNF/TrkB signal pathway. Antioxidant NAC has protective effect upon MG-induced
      neurotoxicity through its antiapoptotic action and its antioxidant effect on ROS
      level. And it works partly by activating the BDNF/TrkB signal pathway.

PMID- 20137607
TI  - [Retention of biological features in human placental mesenchymal stem cells
      transfected by multidrug resistance gene].
AB  - OBJECTIVE: To transfer multidrug resistance gene (mdr1) into human placental
      mesenchymal stem cells (P-MSCs) by retroviral vector and assess the effects of
      mdr1 gene transduction upon biological features of P-MSCs. METHODS: Human P-MSCs
      were isolated from trypsin-digested term placentas and then transduced by
      reconstructed retroviral vector containing mdr1 gene and green fluorescent
      protein (GFP) reporter gene. Flow cytometric analysis was employed to determine
      the immunophenotypes of transfected P-MSCs. And the proliferation and cell cycle
      were detected by methyl thiazolyl tetrazolium and propidium iodide staining.
      Ultrastructures of transfected P-MSCs were observed and different induction
      conditions used to direct the cells to differentiate into adipocytes and
      osteoblasts. RESULTS: The transfected P-MSCs still expressed stem cell markers
      such as CD29, CD44 and CD73. The mean cumulative time of population doubling was
      23.9 hours. The cellular cycle retained the proliferative characterization of
      stem cells. Ultrastructural features of transfected P-MSCs included increased
      surface microvilli, abundant mitochondria and slightly swollen rough endoplasmic
      reticulum. Furthermore these transfected cells demonstrated osteogenic and
      adipogenic differentiation potentials under appropriate conditions. CONCLUSION:
      The mdr1 gene transduction by retroviral vector in vitro has no significant
      effect upon biological characteristics of P-MSCs. It might provide experimental
      references for the application of P-MSCs in high-dose tumor chemotherapy.

PMID- 20137608
TI  - [Investigation in vivo of effect of ultrasound-mediated microbubble destruction
      on entrance of feridex into the aortal wall].
AB  - OBJECTIVE: To explore feasibility for entrance of the contrast agent Sonovue and
      Feridex into the aortal wall. METHODS: 17 male Japanese giant ears rabbits
      (common grade), including 11 atherosclerosis (AS) animal models fed with food
      containing high-content lipid and normal animals fed with common food as control.
      Respectively, 10 animals in the AS group and 6 animals in the normal group were
      selected in a random way to undergo ultrasound-mediated microbubble destruction
      (UMMD) and no ultrasound-mediated microbubble destruction (-UMMD) half and half.
      One animal was administrated with double doses of Feridex. After general
      anesthesia, MR plain scan and intravenous injection of Feridex 100 micromol
      Fe/kg, immediately ultrasound focused on the front wall of the aortic arch, which
      underwent UMMD at the pressure of 3.5 Mpa with MI1.2 while 10 ml solution
      (Sonovue + normal saline)was injected intravenously at the speed of 0.5 ml/min
      FOR 20 min. 3T magnetic resonance (MR) was performed with a moderately T2*
      weighted gradient sequence. Enhanced scan were performed for 1 h, 24 h, 48 h, 72
      h and after killing the animal. then the specimen were delivered to conduct
      optical and electronic microscope examination. Variance test for the re-measured
      data was adopted to verify the data obtained in every group. RESULTS: The effect
      of UMMD group on SPIO particles entrance into the aortal wall is of marked
      significance (P = 0.0004) statistically. The effect of UMMD on distribution in
      the vessel wall is of statistical significance (P = 0.01), more particles in the
      dventitia. Gas or microbubbles were found to enter into the intima, media of the
      aorta, and verified by Oil Red O staining. After staining the findings of iron
      particle in the cell and out of the cell are different. CONCLUSIONS: UMMD may
      facilitate entrance of those SPIO particles with a bigger diameter and
      microbubbles into the aortal wall. This discovery may provide a new solution for
      penetration of complex macromolecule probes and gene-carried drug through the
      tunica intima of the aorta.

PMID- 20137609
TI  - [Experimental radiofrequency ablation in porcine liver ex vivo with "wet"
      unipolar electrode].
AB  - OBJECTIVE: To observe the effects of radiofrequency ablation in porcine liver ex
      vivo with "wet" RITA UniBlate unipolar electrode, evaluate the morphologic
      characteristic of the ablated zones and explore the impact upon the ablation
      lesions of time, temperature and set power of "wet" monopolar electrodes.
      METHODS: The maximal effective ablation electrode length of this "wet" unipolar
      electrode is 2.5 cm. According to ablation time, temperature and power
      respectively, the experiment was divided into three major groups of A, B, C (11
      sub-groups). The investigators observed the morphological characteristics of
      ablation lesions, measured the longitudinal and transverse distance of ablation
      beyond the electrode tip and calculated the volume of ablation lesion.
      Statistical analysis was performed with one-way ANOVA upon the above-mentioned
      four parameters. And the pathological examinations were made with HE staining.
      RESULTS: (1) All of ablated zones were ellipsoid. The cross-section of ablation
      lesions appeared to have 3 zones from the inside out: central zone, coagulated
      zone, hemorrhage and edema zone. (2) When ablating time and temperature increased
      to 15 min and 103 degrees C respectively, the ablated zones peaked: longitudinal
      diameter, transverse diameter, ablation distance beyond electrode tip and volume
      of each ablated zone was (3.49 +/- 0.09) cm, (2.40 +/- 0.13) cm, (0.79 +/- 0.09)
      cm and (10.6 +/- 1.3) cm(3) respectively. With power as a variable, different
      sizes between ablated zones showed no statistical significance. (3) The
      morphology of ablated zones became irregular when the electrodes were located
      around larger blood vessels. CONCLUSION: The ablating time and temperature are
      the major factors of affecting the size of radiofrequency ablation lesion with
      RITA "wet" unipolar electrode.

PMID- 20137610
TI  - [Current situation and existing problem of acute coronary syndrome in China].

PMID- 20137611
TI  - [Improving the diagnosis and treatment skills by establishing new platform of
      gene diagnosis].

PMID- 20137612
TI  - [Evaluation of deaf-mute patients with sensitive deafness gene screening in
      Shandong province].
AB  - OBJECTIVE: To discuss how to determine the number of samples in epidemiological
      study about deafness genes and reveal the characteristics of GJB2, SLC26A4 and
      mitochondrial DNA A1555G mutations in deaf-mute patients in schools for deaf
      mutes in Shandong Province. METHODS: A total of 485 subjects were collected from
      the different schools for deaf-mutes in Shandong province. Amplified target
      fragments included GJB2 coding sequence, mtDNA12SrRNA and exon 8, 10, 17, 19 of
      SLC26A4 gene. The amplicons of mtDNA 12S rRNA were subjected to restriction
      enzyme Alw26I. The amplicons of patients whose enzyme reaction highly indicating
      A1555G mutation, amplicons of GJB2 and those exons PCR products of SLC26A4 were
      directly sequenced. RESULTS: The study revealed that 36.29% patients had two
      mutated alleles (homozygote & compound heterozygote) of GJB2 (24.12%) and SLC26A4
      (6.60%) and mtDNA12SrRNA A1555G (5.57%). The 235delC and IVS7-2A > G were still
      the mutational hot spot in GJB2 and SLC26A4 respectively. CONCLUSION: The method
      of determining the number of sample is very important in the epidemiological
      study. There were about 24 thousand deaf-mute patients who were caused by three
      sensitive deafness genes mutations in Shandong province. Screening the sensitive
      deafness genes in newborn is imminent.

PMID- 20137613
TI  - [Correlation between degree of mitochondrial DNA 1555 mutation and clinical
      phenotype of nonsyndromic hearing loss].
AB  - OBJECTIVE: To study the correlation between the number of mtDNA (mitochondrial
      DNA) copies containing mtDNA A1555G mutation site and phenotype and further
      elucidate the molecular genetic basis of phenotype diversity of nonsyndromic
      hearing loss. METHODS: Real time-amplification refractory mutation system
      quantitative PCR was employed to detect the number of mtDNA copies in mild type
      and mutant type of mtDNA 1555. RESULTS: In the sporadic group, there was no
      significant correlation between mtDNA A1555G homogeneity mutation copies and
      phenotype (R = 0.001, P = 0.997) while significant correlation existed between
      mtDNA A1555G heteroplasmic mutations and phenotype (R = 0.771, P = 0.003). In the
      familial group there was significant correlation mtDNA 1555 homogeneity mutation
      copies and phenotype (R = 0.341, P = 0.022) and significant correlation existed
      between mtDNA 1555 heterogenicity mutation copies and phenotype (R = 0.85, P =
      0.015). CONCLUSION: There is significant correlation between the mtDNA A1555G
      mutation copies and the severity of hearing loss.

PMID- 20137614
TI  - [Molecular etiology of non-syndromic hearing impairment in a Chinese family].
AB  - OBJECTIVE: To investigate the molecular etiology of non-syndromic hearing
      impairment in two patients in a maternal inherited deafness Chinese family.
      METHODS: Peripheral blood specimens were collected and DNA templates extracted.
      The complete mitochondrial genomes and GJB2 gene were sequenced in an ABI 3100
      Avant sequencer. RESULTS: The proband (III-5) and her elder sister (III-1) were
      found to carry the mtDNA 12SrRNA C1494T mutation. The GJB2 gene showed no
      mutations. The proband had the history of using aminoglycosides before hearing
      loss, and exhibited severe sensorineural hearing impairment; the proband's sister
      had no history of using aminoglycosides, and showed moderate sensorineural
      hearing impairment. CONCLUSION: The molecular etiology of each individual patient
      in a family yaries with individual genetic background.

PMID- 20137615
TI  - [Immunological features of fulminant type 1 diabetes].
AB  - OBJECTIVE: To investigate the immunological features of fulminant type 1
      diabetes. METHODS: Twenty patients with fulminant type 1 diabetes (F1D) were
      recruited based upon the criteria proposed by Hanafusa, and 40 patients with
      classical type 1 diabetes were matched with age, gender and duration for
      comparison. GADA, IA2A and ZnT8A were determined with radioligand assay, and GAD
      reactive T cells were measured by enzyme-linked immunospot (ELISPOT) assay. The
      HLA-DQ were analyzed by sequence-based genotyping (SBT). RESULTS: Eight of 20
      patients with F1D were antibody-positive, including 7 GADA positive, 4 ZnT8A
      positive, and 3 both GADA and ZnT8A positive. The index of 3 GADA positive
      patients were less than 0.4 at first visit, two turned to be negative by two or
      three years. While the GADA index of the patient was 0.343 at onset and increased
      to 1.467 three years later. Among subjects with F1D (3/6) and classical type 1
      diabetes (3/6), were recorded significant GAD-stimulated responses by ELISPOT
      assay. The frequencies of HLA-DQA1*0102-DQB1*0601 and DQA1*03-DQB1*0401 were
      significantly higher in F1D than those in classical type 1 diabetes (P = 0.005, P
      = 0.035, respectively). CONCLUSION: Humoral and cellular immunoreactivity and
      susceptible HLA-DQ genotype existed in part of F1D patients, indicating
      autoimmunity may involve in the pathogenesis of F1D.

PMID- 20137616
TI  - [Clinical feature analysis of 190 patients with anti-neutrophil cytoplasmic
      antibodies associated vasculitis].
AB  - OBJECTIVE: To explore the clinical features and disease spectrums for ANCA (anti
      neutrophil cytoplasmic antibodies)-associated vasculitis (AAV) and to improve its
      cognition. METHODS: Clinical features of 190 cases of patients with AAV
      hospitalized from 1998 to 2008 were reviewed retrospectively. According to the
      result of ANCA test, the patients were divided into two groups, cytoplasmic ANCA
      (C-ANCA) positive and perinuclear ANCA (P-ANCA) positive. The authors compared
      the differences of disease spectrums, clinical manifestations and laboratory
      tests between two groups. The relative mortality factors were also analyzed.
      RESULTS: The authors studied 92 males and 98 females with an age range of 8 - 89
      (59 +/- 18) years old. There were 156 cases aged 40 - 80 years old (82.1%) and
      162 patients (85.3%) were of primary AAV including 146 cases of P-ANCA positive
      and 16 cases of C-ANCA positive. There were 28 patients with secondary AAV
      including 18 cases of connective tissue disease, 7 cases of propylthiouracil
      induction, 1 case each of idiopathic thrombocytopenic purpura, lung cancer and
      endometrial carcinoma. There were 25 cases of P-ANCA positive and 3 cases of C
      ANCA positive in secondary AAV. There were 171 cases (90.0%) in P-ANCA group and
      19 cases (10.0%) in C-ANCA group. The number of organ involvement was 2.53 in C
      ANCA group and 1.92 in P-ANCA group. Gastrointestinal tract, joint, upper
      respiratory tract and ocular involvement was more in C-ANCA group than in P-ANCA
      group. Oral and auricular involvement was more in P-ANCA group than in C-ANCA
      group. The involvement difference was of statistic significance in upper
      respiratory tract, joint and eye (all P < 0.05). Renal and pulmonary involvement
      in P-ANCA group was similar to C-ANCA group. There were 3 mortality cases in C
      ANCA group and 22 in P-ANCA group. Respiratory failure and multiple organ
      dysfunctions were relative mortality factors. CONCLUSIONS: AAV is observed in
      elders with multiple organ involvement. The number of organ involvement in C-ANCA
      group is more than that in P-ANCA group. P-ANCA positive patients are more than c
      ANCA patients. The disease spectrum is different in these two groups. Secondary
      AAV is more in P-ANCA group than in C-ANCA group. Clinical manifestations,
      laboratory tests and type of ANCA are helpful for the diagnosis of AAV.

PMID- 20137617
TI  - [Functional improvement of patients with progressive muscular dystrophy by bone
      marrow and umbilical cord blood mesenchymal stem cell transplantations].
AB  - OBJECTIVE: To investigate the feasibility of employing double transplantations of
      autologous bone marrow mesenchymal stem cells (BMSC) and umbilical cord
      mesenchymal stem cells (UMSC) in the treatment of progressive muscular dystrophy
      (PMD). METHODS: A total of 82 cases were treated by the double transplantations
      of BMSC and CB-MSC. They were diagnosed by clinical manifestations, CK, LDH,
      genetic analysis, electromyography, MRI and pathologic examination of biopsied
      muscle specimens from July 2007 to July 2008. Control group was self-made at
      before and after treatment and cases were followed up for 3 - 12 months.
      treatment method: Eighty-two patients underwent the double transplantations of
      bone mesenchymal stem cell (BMSC) and human umbilical cord blood MSC (CB-MSC).
      (1) BMSC: 80 - 150 ml bone marrow sample was collected through a puncture at
      bilateral posterior superior iliac spine. Ficoll density gradient centrifuge was
      employed to separate individual monocyte for induced differentiation. (2) CB-MSC:
      80 - 160 ml umbilical cord blood was harvested and processed likewise as above.
      (3) Stem cell transplantation: Both BMSC and CB-MSC were collected and prepared
      into 1 x 10(8)/ml and 1 x 10(7)/ml cell suspension respectively. They were
      transplanted in divided does into the extremity muscle and vein. The clinical and
      laboratory parameters were monitored at 3, 6, 9 and 12 months. RESULTS: It was
      found that 31 cases (37.8%) obtained a remarkable efficacy, 37 cases (45.1%) were
      effective and 14 cases (17.1%) had no change. Total effective rate was 82.9%.
      Seventy patients (85.4%) felt limbs warmly, appetite improved, gained weight, had
      better appetite and action were nimble. Activity of daily living scale (ADL) in
      72 patients (87.8%) increased as compared with pre-treatment (P < 0.01). LDH
      decreased at post-treatment [(475 +/- 223) u/L vs (410 +/- 216) u/L, P < 0.05, t
      = 6.650]. Creatine kinase [(2952 +/- 2259) u/L vs (2841 +/- 2092) u/L, P = 0.223,
      t = 1.094] and creatine [(26 +/- 12) micromol/L vs (25 +/- 11) micromol/L, P =
      0.306, t = 1.029] decreased slightly. Adherence to therapy among Children and no
      adverse reaction was reported during the course of treatment. CONCLUSION: The
      double transplantation of BMSC and CB-MSC is convenient, safe and effective in
      the treatment of progressive muscular dystrophy and can be considered as a new
      therapy of PMD. MSC represents a possible tool of cellular therapeutics for PMD.

PMID- 20137618
TI  - [A hospital-wide intervention program to optimize the utilization quality of
      carbapenems and glycopeptides].
AB  - OBJECTIVE: To investigate the impact of intervention program upon improvement of
      utilization quality of carbapenems and glycopeptides. METHODS: Multifaceted
      intervention program of carbapenems and glycopeptides was conducted at our
      hospital. It involved written justification forms, expert consultation committee
      meetings, audit, feedback and re-feedback. From November 1, 2007 until October
      31, 2008, retrospective audit and feedback were performed on all patients dosed
      with carbapenems or glycopeptides. Case reports were reviewed and data of ratio
      of appropriate antibiotic use, length of hospital stay, total cost, mortality and
      rate of vancomycin-resistant Enterococci (VRE) were collected and compared
      between the first and second half year of antibiotic intervention program.
      RESULTS: A total of 397 cases were reviewed, 75 cases discussed at expert
      committee meetings and 58 feedback letters delivered to responsible doctors. The
      consumption of both carbapenems and glycopeptides decreased. The appropriate use
      of carbapenems and glycopeptides increased from 37.8% (45/119) to 53.5% (48/127,
      P < 0.05) and from 45.6% (36/79) to 63.9% (46/72, P < 0.05) respectively. The
      total cost and mortality of patients dosed with glycopeptides decreased from a
      median of RMB 65,700 (30,300 - 146,900) yuan to 55,700 (36,700 - 90,900) yuan,
      and from 39.2% to 26.4% respectively. The rate of VRE decreased from 5.63% in
      2007 to 3.80% during the second half year of 2008. CONCLUSION: Antibiotic
      intervention program of carbapenems and glycopeptides is effective in decreasing
      the inappropriate antibiotic use.

PMID- 20137619
TI  - [Clinical observation on the relation between laser in situ keratomileusis
      treating myopic anisometropia and binocular vision].
AB  - OBJECTIVE: To analyze the effect of LASIK on visual quality of anisometropia, and
      evaluate its clinical value in the view of visual quality. METHODS: Prospective
      observational case series. Assayed the naked vision, glasses-corrected vision and
      binocular vision of 45 cases with anisometropia >or= 2.25D before and after the
      operation of LASIK. RESULTS: 91.57% of the eyes after the operation reached the
      vision >or= 0.8, which says a significant improvement for binocular vision after
      the operation (P < 0.05). There was a significant difference on diopter between
      the pre-operation and post-operation (P < 0.05). As for anisometropia, there was
      no significant difference between simultaneous binocular visions (P = 0.431), but
      there was of great significance among combined, short and long distance
      stereopsis visions (P = 0.000). Binocular vision deteriorated as anisometropia
      increased (P < 0.05). The short distance stereopsis visions of LASIK-treated
      myopic anisometropia were better than that of glasses-corrected patients (P <
      0.05). CONCLUSION: The operation of LASIK can improve the visual quality and
      resume the binocular vision. LASIK can correct anisometropia and its therapeutic
      efficacy deserves to confirm.

PMID- 20137620
TI  - [Long-term therapeutic effect of Zenapax after renal transplantation].
AB  - OBJECTIVE: To determine whether there was any lingering effect after
      discontinuing Zenapax in renal transplantation and investigate there was any
      alternative immunity-regulating pathway of Zenapax other than IL-2/IL-2R.
      METHODS: Thirty patients of renal transplantation were divided into 2 groups. One
      group of 15 received 2 dosages of induction therapy of Zenapax and another 15
      regular immunosuppressive therapy. IL-2, IL-10, STAT5 and CD40L were tested
      followed up at 2 hours pre-transplantation, 1, 3 and 6 months post
      transplantation. RESULTS: The levels of IL-2 and STAT had no difference between
      the induction group and the control group. The level of IL-10 of induction group
      (59.4 +/- 7.7) ng/L was obviously higher than control group (36.8 +/- 8.4) ng/L
      at 3 months post-transplantation. CD40L level of induction group (10.6 +/- 3.6)
      was lower than control group (35.6 +/- 8.4) at 1 month post-transplantation.
      CONCLUSION: Zenapax can reduce B-cell-mediated humoral immunity at 1 month post
      transplantation through CD40L pathway.

PMID- 20137621
TI  - [Optimizing effect of infliximab upon inflammatory bowel disease].
AB  - OBJECTIVE: To explore the optimal therapeutic effect of infliximab (IFX) upon
      inflammatory bowel disease. METHODS: Eight patients with inflammatory bowel
      disease (IBD), including 5 Crohn's disease (CD) and 3 ulcerative colitis (UC),
      were treated with IFX of 5 mg/kg body weight at 0, 2 and 6 weeks, followed by
      scheduled maintenance therapy every 8 weeks and followed up for a long-term
      period. Of these patients, 5 cases were resistant to corticosteroid, 2 cases
      corticosteroid dependency and one naive patient. RESULTS: All patients responded
      well to the scheduled program of 5 mg/kg infusion of IFX. Two CD cases achieved a
      complete remission. Two CD patients responded clinically; one was difficult to
      judge the result; of the UC patients, one achieved a complete remission and 2
      responded. There were no serious side effects during the course of therapy.
      CONCLUSION: Selecting the proper drug indications and therapeutic protocol,
      determining the doses and course of IFX on the basis of therapeutic response,
      combining IFX with other immunomodulators (esp. budesonide) and assessing the
      therapeutic efficacy of IFX by endoscopic mucosa healing rather than symptoms
      prevent disease recurrence and decrease side effects.

PMID- 20137622
TI  - [Feasibility of transurethral electro-resection as sole modality for the
      treatment of cystitis glandularis].
AB  - OBJECTIVE: To evaluate the efficacy and necessity of transurethral electro
      resection as sole modality for the treatment of cystitis glandularis. METHODS:
      The clinical data of 48 cases were reviewed. The patients were divided into two
      groups. One control group of 25 cases was treated by transurethral electro
      resection or electric coagulation combined with bladder instillation of anti
      tumor drugs. The other investigation group of 23 cases was treated by
      transurethral electro-resection as sole modality. The cystoscopy was performed at
      3 months post-operatively to judge if the disease recurred. And the efficacy of
      two groups was compared. RESULTS: In the control group, 21 cases had normal
      cystoscopic finding and the rate of lesion removal was 84%, cure rate 72% and
      efficacy rate 92%. In the investigation group, 19 cases had normal cystoscopic
      finding and the rate of lesion removal was 83%, cure rate 74% and efficacy rate
      87%. There was no statistical significance between these two groups. CONCLUSION:
      Using transurethral electro-resection as a major therapy without bladder
      instillation of anti-tumor drugs is feasible. It can reduce the hospitalization
      cost and economize the social resources.

PMID- 20137623
TI  - [Molecular cloning of a novel gene, C5orf21 gene and its roles in diabetic
      macroangiopathy].
AB  - OBJECTIVE: To clone a novel diabetic angiopathy related protein gene-C5orf21 and
      study its roles in diabetic macroangiopathy. METHODS: The open reading frame
      (ORF) of C5orf21 gene was cloned into vector from human aortic tissues by a RT
      PCR-based approach and identified by enzyme-cutting and sequencing. The structure
      and function of C5orf21 gene and protein were further analyzed by bioinformatics
      technology. The mRNA expression of C5orf21 gene in human tissues and in vascular
      cells was analyzed by RT-PCR. RT-PCR was used to observe the effect of high
      glucose, low-density lipoprotein (LDL) and free fatty acid (FFA) upon the
      expression of C5orf21 gene in macrophages. RESULTS: C5orf21 gene was successfully
      inserted into pDrive vector and identified for the first time at the level of
      mRNA. There are five C5orf21 gene splice variants in human aortic tissue and
      their length of ORF are 1251, 1113, 894, 810 and 810 bp respectively. Two kinds
      of splice variants have yet to be included in GenBank database. Two kinds of
      splice variants have the same ORF and their differences are mainly in the bases
      in the 5' untranslated region. Bioinformatics analysis found that C5orf21 gene
      was located in chromosome 5q15 and C5orf21 protein contained Arb2 domain
      associated with histone H3 lysine 9 methylation. C5orf21 gene was normally
      expressed in many tissues. Fat and aortic tissues had the highest expression. The
      expression of C5orf21 gene could be detected in human aortic endothelial cell,
      aortic smooth muscle cell and macrophages. High glucose, LDL and FFA (esp.high
      glucose) up-regulated the expression of C5orf21 gene in macrophage. CONCLUSION:
      C5orf21 gene contains five splice variants and it is identified for the first
      time at the level of mRNA. The changes of C5orf21 gene expression are correlated
      with diabetic macroangiopathy.

PMID- 20137624
TI  - [Establishment of animal model of myoclonus originating from axis of cortex
      thalamus].
AB  - OBJECTIVE: To develop a series of experimental animal models of myoclonus with
      different origins consistent with myoclonus seizure in clinic setting. METHODS:
      GABA(A) antagonist SR95531 was microinjected into the primary motor cortex (PMC),
      corpus striatum, nucleus reticular of the thalamus (NRT) to induce myoclonus (EMG
      burst of myoclonus <or= 400 ms). The behavior characteristics including latency,
      peak time, duration of seizure peak, maximal seizure frequency and total duration
      were observed. EMGs and ictal EEGs were recorded synchronously. The origin of
      myoclonus and its correlation with epileptic discharges were further confirmed by
      jerk-locked back averaging (JLA). A group of rats were pretreated with VPA, CZP
      and CBZ at the doses corresponding to their EC(50). Myoclonus was induced at the
      time when the drug level was within their effective anticonvulsion concentration.
      The changes of behaviors and neuroelectrophysiological characteristics of
      myoclonus after pretreatment of AEDs were observed. RESULTS: (1) The myoclonus
      originating from PMC had the shortest latency and time to reach its peak as well
      as the longest duration of peak duration [(2.2 +/- 0.4), (15.0 +/- 2.5), (98 +/-
      12) min]. The myoclonus originating from PMC and corpus striatum usually started
      from forelimb contralateral to injection. On the contrary, the myoclonus arising
      from NRT affected mainly the limb ipsilateral to the microinjection. (2) The EMG
      burst duration of myoclonus was (70 +/- 14) ms (PMC), (120 +/- 28) ms (corpus
      striatum) and (174 +/- 58) ms (NRT) respectively (F = 9.48, P < 0.01). All of
      them were accompanied with synchronic and regular spike or sharp discharges in
      EEG. (3) All the myoclonus originating from PMC, corpus striatum and NRT acquired
      time-locked cortical waves in average were ahead of their synchronous EMG (12.1
      +/- 2.9) ms, (17.1 +/- 4.3) ms and (29.0 +/- 6.1) ms respectively. (4) Under
      EC(50) concentration of those AEDs: VPA and CZP decreased the maximal seizure
      frequency of myoclonus originating from PMC, corpus striatum and NRT respectively
      (P < 0.01 or P < 0.05); the duration of peak time and the total time of myoclonus
      arising from PMC and corpus striatum were shortened notably, but there was no
      significant influence of NRT upon myoclonus. The duration of peak time and total
      time of myoclonus seizures were remarkably extended by CBZ (P < 0.01 or P <
      0.05). CONCLUSION: A series of experimental myoclonus models of different origins
      are successfully established. They are consistent with the mechanism, behavior,
      neuroelectrophysiological and pharmacodynamic characteristics of clinic
      myoclonus.

PMID- 20137625
TI  - [Effects of glucose and insulin in the cell differentiation from bone marrow stem
      cells to osteoblasts].
AB  - OBJECTIVE: To observe the effects of different concentrations of glucose and
      insulin in cell differentiation from bone marrow stem cells (BMSC) into
      osteoblasts (OB) and explore the acting mechanism of glucose and insulin in bone
      metabolism. METHODS: The in vitro technique of cell culture was employed to
      separate, purify and cultivate BMSC from the tibia and femur of rats. Then the
      BMSCs were differentiated into osteoblasts under the inductions of different
      glucose concentrations (5.6, 25, 50 mmol/L) with or without the addition of
      insulin (0.6 microg/ml). Later the calcium nodule cell ratio of osteoblasts in
      alizarin red stain was observed microscopically to assay the mRNA expression of
      OB markers-ALP, BGP and Runx2 by real-time PCR. RESULTS: With the increasing
      glucose concentrations, the number of red calcium nodules obviously decreased.
      PCR showed that the mRNA expression of ALP, BGP and transcription factor Runx2
      decreased too. The difference was significant (P < 0.05). The differentiation of
      OB decreased with with the increasing glucose concentrations. The cell number of
      red calcium nodules obviously increased in the same glucose concentration groups.
      The mRNA expression of ALP, BGP and Runx2 also increased (P < 0.01). It hinted
      that insulin could enhance the differentiation of OB. CONCLUSION: Glucose can
      inhibit the differentiation from BMSC into OB. The inhibition is more sensitive
      along with the concentration increments. This may be one of the pathogenesises of
      diabetic osteoporosis. Insulin can enhance the differentiation from BMSC into OB.
      In addition, it can improve the inhibition of differentiation from BMSC into OB
      because of a high concentration of glucose.

PMID- 20137626
TI  - [More attention to individualized comprehensive therapy of myasthenia gravis].

PMID- 20137627
TI  - [Expression of regulatory T cells in thymus of myasthenia gravis patients].
AB  - OBJECTIVE: To investigate the in situ expression of regulatory T cells (Tregs) in
      thymus and its significance for myasthenia gravis (MG). METHODS: Thirty nine MG
      patients who had not accepted immunosuppressive therapy before thymectomy were
      recruited as study group and 19 patients undergoing cardiosurgery as control.
      There was no significant statistical difference in age and gender between the two
      groups (P > 0.05). The location and proportion of Tregs in thymus were analyzed
      using indirect immunofluorescence double labeling immunohistochemistry and image
      analysis software. RESULTS: (1) Tregs were all located in medulla zone of thymus
      in control and MG groups. (2) Cells of germinal center had a high expression of
      CD25 and a low expression of CD4. It indicates that a majority of germinal center
      cells were B cells. (3) There were fewer Tregs around germinal center. (4) There
      was no statistical significant difference in absolute number of Tregs between the
      two groups (P > 0.05). But the proportion of Tregs was higher in control group (P
      < 0.05). CONCLUSION: The proportion of thymus Tregs decreases in MG so as to
      weaken the function of immuno-regulation and suppression. This is probably a
      precipitating factor of MG.

PMID- 20137628
TI  - [Association of glucocorticoid receptor gene polymorphism with myasthenia
      gravis].
AB  - OBJECTIVE: To investigate the association of two glucocorticoid receptor (GR)
      polymorphisms (BclI, ER22/23EK) with Myasthenia Gravis (MG). METHODS: The
      genotypes of GR in 61 MG patients (MGG) and 57 age and gender-matched healthy
      controls (HCG) were determined by polymerase chain reaction and nucleotide
      sequence determination. RESULTS: The frequencies of three genotypes (GG, CG, CC)
      in BclIwere 3.3%, 34.4%, 62.3% in MGG and 3.5%, 38.6%, 57.9%in HCG respectively.
      The difference in the distribution of genotypes between MGG and HCG was
      statistically insignificant (P = 0.887). The frequencies of G and C allele were
      20.5% vs 79.5 %in MGG, and 22.8% vs 77.2% in HCG. The difference in the
      distribution of alleles between MGG and HCG was statistically insignificant (P =
      0.968). The genotype frequencies in two groups were both in Hardy-Weinberg
      equilibrium (P > 0.05). The genotypes of ER22/23EK in MGG and HCG were all GG and
      no mutation was detected. CONCLUSION: BclI and ER22/23EK polymorphisms of GR have
      no definite relationship with the risk of MG.

PMID- 20137629
TI  - [Relationship between polymorphism sites of IRF5, TLR-9 and SLE patients in
      Shandong Han population].
AB  - OBJECTIVE: To investigate two single nucleotide polymorphism sites of IRF5 and
      TLR-9 and to detect their relationship with SLE (systemic lupus erythematosus) in
      a Han population from Shandong province. METHODS: The polymorphisms of rs2004640
      G/T, rs10954213 G/A in IRF-5 and rs187084C/T, rs352139A/G in TLR-9 were detected
      with PCR-RFLP in 92 cases of SLE and 88 healthy controls. The genotype and allele
      frequencies were calculated and analyzed. RESULTS: (1) The genotype frequencies
      of GG, GT and TT in rs2004640 site in SLE were 0.198, 0.521 and 0.281
      respectively. The difference was significant between SLE and controls (chi(2) =
      8.73, P < 0.05); the genotype frequencies of GG, GA and AA at rs109542130 site in
      SLE were 0.318, 0.409 and 0.273 respectively. The difference was significant
      between SLE and controls (chi(2) = 6.36, P < 0.05). (2) The genotype frequencies
      of CC, CT and TT at rs187084 site in SLE were 0.185, 0.413 and 0.402
      respectively. There was no difference between SLE and controls (chi(2) = 2.99, P
      > 0.05); the genotype frequencies of AA, AG and GG at rs352139 site in SLE were
      0.228, 0.533 and 0.239 respectively. There was no difference between SLE and
      controls (chi(2) = 4.54, P > 0.05). CONCLUSION: The polymorphism of rs2004640 and
      rs10954213 in IRF5 may be associated with SLE in the population of Han
      nationality from Shandong province. However, the polymorphism of rs187084 and
      rs352139 in TLR-9 is not associated with SLE.

PMID- 20137630
TI  - [Early glucose challenge test in pregnant women with risk factors of GDM in
      China].
AB  - OBJECTIVE: To understand the current status and clinical relevance of early (<24
      weeks) glucose challenge test (GCT) in pregnant women with risk factors of
      gestational diabetes mellitus (GDM) in China. METHODS: Data from the survey of
      incidence of GDM in China were re-analyzed. The incidence of abnormal glucose
      metabolisms and the rate of early GCT in all women were calculated according to
      different numbers of risk factors. Sixteen risk factors were included in the
      survey. However, 4 independent risk factors were considered separately in this re
      analysis. The ADA criteria for GDM diagnosis were applied. RESULTS: A total of 16
      286 pregnant women were included in this analysis and 64.3% (10 468) presented
      with at least one risk factor. The incidence of GDM became elevated with the
      increasing number of risk factors (P < 0.001). Early GCT was performed in 1687
      (16.1%) pregnant women and the early detected GDMs only accounted for 11.9% of
      all GDMs among those with at least one risk factor. Among those who had early
      GCT, the GDM diagnosis rate increased with the number of risk factors (P <
      0.001). Previous analysis in this survey identified 4 independent risk factors
      for GDM among 16 risk factors: BMI > or = 24, age over 30 years old, family
      history of DM and southerners. Similar analysis was performed according to the
      above 4 risk factors and similar results were found as those found for 16 risk
      factors. No significant difference was found in the GDM and GIGT incidence
      between the two analyses in those with at least one risk factor. CONCLUSION:
      Early GCT is necessary for pregnant women with risk factors of GDM, but the
      screening rate in China is low. GCT should be repeated for those women with risk
      factors of GDM and normal GCT at early screening.

PMID- 20137631
TI  - [Study of spinal sagittal plane curve in patients with thoracolumbar
      intervertebral disc herniation].
AB  - OBJECTIVE: To understand the curve of thoracolumbar junction in patients with
      thoracolumbar intervertebral disc herniation and analyze the relation between
      thoracolumbar intervertebral disc herniation and spinal sagittal curve. METHODS:
      The radiographic films of thoracolumbar junction of spine from 27 patients with
      thoracic disc herniation and 37 healthy persons as control were taken at
      reclining position. The Cobb angles of sagittal plane of thoracolumbar junction
      of spine were measured and statistically compared by SPSS (statistics package for
      social science). RESULTS: The Cobb angles of T10-L2, T10-L12 and T12-L2 in
      patients with thoracolumbar intervertebral disc herniation were greater than
      those in healthy controls respectively. CONCLUSION: The Cobb angles of sagittal
      plane of thoracolumbar junction of spine in patients with thoracolumbar
      intervertebral disc herniation are greater than those in healthy controls. The
      abnormal spinal curve is possibly responsible for thoracolumbar intervertebral
      disc herniation by abnormal biomechanical action.

PMID- 20137632
TI  - [Comparison of multiple point stimulation and incremental stimulation in patients
      with amyotrophic lateral sclerosis].
AB  - OBJECTIVE: To compare two common techniques for motor unit number estimation
      (MUNE), multiple point stimulation and incremental stimulation to determine which
      is preferable in patients with amyotrophic lateral sclerosis (ALS). METHODS:
      Surface recorded motor unit action potentials of median nerve or thenar muscle
      were measured in 60 ALS patients and 60 controls. The maximal baseline to
      negative peak compound muscle action potential (CMAP) amplitude was recorded. For
      multiple point stimulation, the stimuli sites included the skin of wrist, 6 cm
      above the wrist, elbow and 6 cm above the elbow. Individual motor unit responses
      were obtained by moving the stimulating electrode and isolating threshold
      responses with distinct morphologies. Then, with finely graded stimulus intensity
      at one point, 3 steps in a CMAP were investigated. 10 - 12 different single motor
      unit action potentials (SMUPs) were recorded. For incremental stimulation,
      stimulus intensity was slowly increased from subthreshold levels until a small
      all-or-none response was evoked. The intensity was slowly increased until the
      response increased in a quantal fashion. This process was repeated for a total of
      10 increments. Individual motor unit amplitudes were obtained by subtracting
      amplitudes of each response from that of prior response. Both techniques were
      performed twice, electrodes changed and results averaged. RESULTS: For controls,
      MUNE was 228 +/- 30 for multiple point stimulation and 198 +/- 26 for incremental
      stimulation. Test-retest correlation coefficients and coefficients of variation
      for mean of two MUNE were 0.88 - 0.91 and 13.20% - 15.24% for multiple point
      stimulation, 0.86 and 13.30% - 15.65% for incremental stimulation. For ALS
      patients, MUNE was 64 +/- 6 and 59 +/- 7 respectively. CONCLUSION: Both MUNE
      methods are similarly reproducible and are equally effective at documenting
      progression of a lower motor neuron disorder in ALS patients.

PMID- 20137633
TI  - [Meta-analysis on relationship between hyperhomocysteinemia and multiple
      sclerosis].
AB  - OBJECTIVE: To determine the relationship between hyperhomocysteinemia and
      multiple sclerosis (MS). METHODS: Cochrane, Medline, EMbase, Springerlink,
      Highwire, CBM, CNKI and some other databases were searched for literatures.
      Articles were identified using the Medical Subject Heading term
      "hyperhomocysteinemia, homocysteine, multiple sclerosis". The methodological
      quality of internalized literatures were evaluated, screened and heterogeneity
      tested. Case control studies involving unrelated subjects and valid data were
      extracted and analyzed in Stata 8.0. RESULTS: Nine studies were included in this
      review. The involved 1146 subjects were made of 676 patients and 470 controls. A
      meta-analysis showed that the level of homocysteine in MS was higher than that in
      controls (standardized mean difference 1.25, 95%CI: 0.48 - 2.01). The analytical
      result of sensitivity proved that the result of meta-analysis was coherent.
      CONCLUSION: Hyperhomocysteinemia is associated with MS, and it may contribute to
      the pathological course of MS.

PMID- 20137634
TI  - [Expression and function of Cx32 and Cx43 junctions in medically intractable
      temporal lobe epilepsy in human].
AB  - OBJECTIVE: To study the expression of Cx32 and Cx43 in medically intractable
      temporal lobe epilepsy in human and investigate the pathogenic relationship
      between gap junctions and seizures. METHODS: The expression of Cx32 and Cx43 was
      detected by Western blot and immunohistochemistry in 14 consecutive samples of
      hippocampus from epileptic patients undergoing an amygdalohippocampectomy for the
      treatment of intractable seizures. During postmortem dissection, 8 samples of
      hippocampus in nonepileptic patients dying of other diseases were taken as
      control group. RESULTS: The expression of Cx32 and Cx43 was at a low level in the
      control group [Cx32: count of positive cell (9.4 +/- 1.1), ratios of gray scale
      (0.2 +/- 0.1); Cx43: count of positive cell (9.2 +/- 4.7), ratios of gray scale
      (0.5 +/- 0.2)], but Cx43 and Cx32 appeared to be expressed at a higher level in
      epileptic patients compared with that of the control group by
      immunohistochemistry [Cx32: count of positive cell (14.6 +/- 3.4), Cx43: count of
      positive cell (16.5 +/- 3.1)] (P < 0.01), and their expression significantly
      increased by Western blot [Cx32: ratios of gray scale (1.5 +/- 0.2), Cx43: ratios
      of gray scale (1.4 +/- 0.3)] (P < 0.01). Over-expression of Cx32 and Cx43 was
      found in 14 consecutive samples of hippocampus from epileptic patients.
      CONCLUSION: Gap junctions play an important role in the occurrence and
      progression of intractable seizures.

PMID- 20137635
TI  - [Diagnosis and treatment of pulmonary sequestration].
AB  - OBJECTIVE: To explore the clinical manifestations and treatment of pulmonary
      sequestration. METHODS: Thirty-five patients with pulmonary sequestration
      confirmed by pathological studies were analyzed. RESULTS: Among these patients,
      29 were of intralobar type and 6 of extralobar type. All patients of intralobar
      type had symptoms of cough, expectoration, fever and hemoptysis while 6 cases of
      extralobar type were asymptomatic. Twenty-three cases were diagnosed
      preoperatively by enhanced CT scan, CT angiography or selective arteriography.
      Success of operation had been achieved in all cases. CONCLUSION: The clinical
      manifestations of pulmonary sequestration are non-specific. Though invasive,
      selective arteriography plays a decisive role in the diagnosis. Such non-invasive
      angiographies as enhanced CT scan and CT angiography have become important
      supplements to it. Once the diagnosis is confirmed, operation should be
      performed.

PMID- 20137636
TI  - [Extraanatomic aortic bypass grafting for the treatment of complex aortic
      coarctation].
AB  - OBJECTIVE: To review the experience of extraanatomic aortic bypass grafting for
      the treatment of complex aortic coarctation. METHODS: From July 1997 to July
      2008, 48 consecutive patients (median age 30 years; range 10 to 58 years) with
      complex aortic coarctation underwent extraanatomic aortic bypass grafting.
      Indications include: (1) coarctation with intracardiac anomaly (n = 28); (2)
      coarctation with ascending aortic aneurysm (n = 1); (3) adult coarctation with
      calcification of local aortic wall (n = 7); (4) coarctation with hypoplasia
      aortic arch (n = 4); (5) long or multiple coarctation segment (n = 4); (6)
      coarctation with poststenotic aneurysm (n = 1); and (7) recurrent coarctation (n
      = 3). Routing of the grafts was:ascending-to-posterior pericardial descending
      aorta (n = 37); ascending-to-infrarenal abdominal aorta (n = 9); left subclavian
      artery-to-descending aorta(n = 2). Concomitant cardiac operations were performed
      in 31 patients (65%) using cardiopulmonary bypass; procedures included: aortic
      valve replacement in 16; mitral valve repair or replacement in 9; Bentall
      procedures in 6; patent ductus arteriosus closure in 5; ascending aortic
      replacement or plasty in 4; ventricular septal defect closure in 3 and coronary
      artery bypass surgery in 2. RESULTS: There was no operative death. One patient
      died of septic shock 39 days postoperatively. Two patients received laparotomy
      because of mechanical ileus shortly after the ascending-to-subrenal abdominal
      aortic bypass. Mean systolic blood pressure gradient between upper and lower
      extremities decreased from (65 +/- 27) mm Hg preoperatively to (14 +/- 11) mm Hg
      postoperatively (P < 0.05). During a mean follow-up of 28.9 months, there were no
      late deaths or graft-related complications. Residual mild hypertension were
      observed in five patients. CONCLUSION: Extraanatomic aortic bypass is an
      attractive treatment option for complex aortic coarctation in adults and
      adolescents. It can be performed with low morbidity and mortality. The midterm
      results is favorable.

PMID- 20137637
TI  - [Down-regulating effect of hepatitis B virus pre-S2 protein upon insulin receptor
      gene promoter].
AB  - OBJECTIVE: To investigate the down-regulating effect of HBV pre-S2 protein upon
      insulin receptor (INSR) gene promoter. METHODS: Eukaryotic expression plasmid
      pcDNA3.1(-)-preS2 and report plasmid pCAT3-INSRp containing INSR gene promoter
      upstream of CAT gene were constructed with routine molecular biological methods
      and were confirmed by endonuclease digestion analysis and sequencing. Then HepG2
      cells were transfected with pcDNA3.1(-)-preS2 plasmid and the total RNAs were
      examined with relative quantitative real-time PCR to confirm the expression of
      HBV pre-S2 protein. Later HepG2 and Huh7 cells were transfected with pCAT3-INSRp
      at various doses (0 - 2.0 microg). The choloraphenical acetyltransferase (CAT)
      activity of transfected cells was detected with CAT-ELISA to generate the dose
      effect curve of pCAT3-INSRp. Lastly pCAT3-INSRp (1.0 microg) and pcDNA3.1(-)
      preS2 (1.0, 1.5, 2.0, 2.5, 3.0 microg) were co-transfected into HepG2 and Huh7
      cells respectively to study the regulation effect of pre-S2 protein upon INSR
      promoter. Meanwhile pre-S2 monoclonal antibody was added into additional cells
      transfected with 2.0 microg of pcDNA3.1(-)-preS2 plasmid to evaluate the effect
      when pre-S2 protein was blocked. RESULTS: The mRNA of pre-S2 protein could be
      detected with real-time PCR indicating that pre-S2 protein was properly expressed
      in pcDNA3.1(-)-preS2-transfected cells. The expression of CAT increased
      proportionally with the incremental doses of pCAT3-INSRp. It suggested that the
      INSR gene promoter had its transcription activity. After co-transfection of pCAT3
      INSRp and pcDNA3.1(-)-preS2, the CAT expression in HepG2 cells, comparing with
      that of controls, were 69.8%, 60.1%, 19.7%, 10.3%, 5.6% (36 h) and 68.6%, 56.0%,
      10.3%, 8.6%, 3.2% (72 h) respectively. When pre-S2 monoclonal antibody was added
      into the supernatant of HepG2 cells transfected with 2.0 microg of pcDNA3.1(-)
      preS2, the CAT expression was partly restored to 55.4%(36 h)and 69.7%(72 h)of
      controls. The similar results were observed in Huh7 cells. CONCLUSION: The pre-S2
      protein down-regulates the activity of INSR gene promoter so as to reduce the
      expression of INSR. It may partly elucidate the pathogenesis of hepatogenous
      diabetes at the molecular level.

PMID- 20137638
TI  - [Construction of rat constitutively active recombinant caspase-3 and
      investigation of its pro-apoptotic effect in vitro].
AB  - OBJECTIVE: To investigate the apoptosis induction effect by the rat recombinant
      caspase-3. METHODS: Reversed rat caspase-3 gene was gained by settling the small
      subunit prior to the large one through recombinant PCR, and cloned into the
      expression vector to transfect human 293T cells and rat immortalized neural
      progenitor cells. The expression and pro-apoptotic effect of recombinant caspase
      3 was observed by the changes of morphology of the transfected cells through
      immunofluorescence and analyzed by Annexin V-FITC staining, Flowcytometry and MTT
      assay. RESULTS: The transfected cells presented obvious apoptosis as detected by
      immunofluorescence. MTT assay showed that the proliferation of recombinant
      caspase-3 transfected cells was significantly inhibited [(48.35 +/- 0.16)%,
      (44.61 +/- 0.15)%] (P < 0.05). Annexin V-FITC staining revealed that the
      percentage of apoptotic cells in the transfectants of recombinant caspase-3 gene
      was [(30.7 +/- 1.5)%, (16.0 +/- 1.0)%] (P < 0.05), which was much higher than
      that of control cells. CONCLUSIONS: Rat recombinant caspase-3 can be expressed
      and induce apoptosis effectively, and used safely both in vitro and in vivo. It
      can also cause neural cells to death.

PMID- 20137639
TI  - [The sonic hedgehog induce vascular adventitial fibroblasts phenotypic
      modulation, proliferation and migration].
AB  - OBJECTIVE: To study the effect of shh on the migration, proliferation and
      phenotypic modulation of vascular adventitial fibroblasts. METHOD: Cultivate the
      vascular adventitial fibroblast in vitro. Use immunofluorescent, laser confocal
      microscopy, Western-blot and real-time PCR to detect the expression of mRNA and
      protein of related index. Estimate cell proliferation according to the expression
      of Ki67 and cell proliferation curve. Application of wound healing test to
      estimate migration of fibroblast. The expression of alpha-actin is thought to be
      marker of phenotypic modulation of fibroblast. RESULT: The expression of shh was
      detected in vascular adventitial fibroblast in vitro. After addition of exogenous
      shh (3.5 microg/ml), there were more Ki67(+) cells and the wounding area which
      was covered by cells became larger. The expression of alpha-actin was detected.
      After addition of cyclopamine (40 micromol/L), there were less Ki67(+) cells and
      the wounding area which was covered by cells became smaller. CONCLUSION: Shh can
      promote proliferation, migration and phenotypic modulation of vascular
      adventitial fibroblasts.

PMID- 20137640
TI  - [Experimental study on tissue engineering platelet lysates in the promotion of
      bone reconstruction].
AB  - OBJECTIVE: To evaluate the effects of tissue engineered allogeneic platelet
      lysates (PL) upon bone reconstruction. METHODS: After preparation of recombinant
      material with PL, allogeneic decalcified bone granules (ADBG) and collagen type I
      (CG), 30 healthy Wistar rats were used to prepare the bilateral bone defects in
      femoral condyles. The defects were filled with equivalent PL/ADBG/CG, ADBG/CG and
      CG in different groups of A, B and C (with 10 rats each) respectively. At 4
      weeks, the defect reconstruction was evaluated with radiology, histology,
      immunology and biomechanics. RESULTS: (1) The X-ray showed that bone density in
      group A (4.18 +/- 0.96) was close to that of normal bone and it was significantly
      higher than that in group B (2.36 +/- 0.87) and group C (1.09 +/- 0.55) (P <
      0.01). (2) In comparisons with B and C, the histological assay revealed that
      there were markedly more activities of new bone formation and more implanted bone
      granules surviving without significant lymphocyte infiltration, as well as more
      osteoclastic bone resorption in group A. The bone histomorphometric assay showed
      the newly formed bone area in group A (286.73 +/- 17.22) was significantly higher
      than that in group B (94.34 +/- 33.56) and group C (19.12 +/- 14.53) (P < 0.01).
      (3) Anti-press mechanical measures showed that the destructive load in A, B, C
      and normal control group was 259.63 +/- 34.57, 187.90 +/- 21.07, 91.33 +/- 26.58
      and 311.93 +/- 82.45 respectively. The destructive energy in A, B, C and normal
      control group was 10.82 +/- 1.44, 7.83 +/- 0.88, 3.81 +/- 1.11 and 12.97 +/- 3.43
      respectively. These results showed either destructive load or destructive energy
      in group A was markedly higher than that in group B and group C with significant
      difference (P < 0.01), but still lower than that in normal controls (P < 0.01).
      (4) Three-color flow cytometry assay showed that the T lymphocyte subsets of
      CD3+CD4+CD8-, CD3+CD8+CD4- and the ratio of CD4/CD8 showed no significance
      difference within these three groups as well as normal controls. CONCLUSION:
      Tissue engineering PL (PL/ADBG/CG) is capable of accelerating the regenerative
      repair of bone defect and promoting the bone regeneration and osetointergretion
      of allograft bone after transplantation.

PMID- 20137641
TI  - [Surgical strategy of atlantoaxial dislocation].

PMID- 20137642
TI  - [Relationship of dynamic cord impingement with disease severity and prognosis in
      cervical spondylotic myelopathy].
AB  - OBJECTIVE: To investigate the relationship of dynamic cord impingement of
      sagittal diameter on flexion-extension cervical magnetic resonance (MR) imaging
      with disease severity and prognosis in cervical spondylotic myelopathy. METHODS:
      A total of 53 patients with cervical degenerative disease were evaluated with
      regards to the dynamic cord changes of sagittal diameter at neutral and flexion
      extension 1.5 T MR imaging from February 2006 to November 2008. The mean follow
      up period was 14.6 (11 - 36) months. The factors of age, sex, duration of
      disease, cervical range of motion and cord signal intensity were considered. The
      patients were divided into two groups according to the extent of dynamic cord
      changes of sagittal diameter on MRI (groups of high and low dynamic cord
      changes). Statistical analyses were performed with SPSS 13.0. RESULTS: The
      preoperative JOA scores were 9.17 +/- 2.45 and 13.76 +/- 2.81 respectively with a
      recovery rate of 57.02% +/- 16.23% at the final follow-up. There was no
      significant difference between the two groups in terms of recovery rate and age.
      The cervical range of motion and cord signal intensity in group of high dynamic
      cord changes were higher than those in group of low dynamic cord changes. The
      preoperative JOA score and duration of disease were lower than those in group of
      low dynamic cord changes. According to linear regression test between the
      recovery rate, the preoperative JOA score and the extent of dynamic cord changes,
      the correlation coefficient were 0.07 (P = 0.643) and -0.27 (P = 0.04)
      respectively. CONCLUSION: With the precondition of a short disease duration in
      cervical spondylotic myelopathy, the extent of dynamic cord changes is correlated
      with disease severity but shows no relationship with prognosis.

PMID- 20137643
TI  - [Association study of SIM2 gene polymorphisms with susceptibility to congenital
      scoliosis in a Chinese Han population].
AB  - OBJECTIVE: To investigate whether polymorphisms of SIM2 gene are associated with
      congenital scoliosis (CS) in a Chinese Han population. and explore the
      relationship of between polymorphisms of SIM2 and clinical phenotypes of CS.
      METHODS: A case-control design was employed in this study. A total of 127
      patients (55 boys, 72 girls, mean age 12.90 y/o) diagnosed with CS admitted at
      Peking Union Medical College (PUMC) Hospital were enrolled between October 2005
      and September 2007. The scoliosis-free control subjects (127 cases) at the same
      hospital during the same study period were frequency-matched to the cases on age
      (+/- 3 years) and gender. Genomic DNA was extracted by QIAamp DNA Blood Mini Kit
      from peripheral blood leukocytes of each subject who had signed informed consent.
      Based on genotype data from the International HapMap project, the main functional
      single nucleotide polymorphisms (SNPs) initially were selected. Case group were
      classified into different clinical phenotypes according to vertebral defect type,
      location of deformity, extent of developmental disruption, combined rib
      malformations and neural canal deformity. Genotying of all selected SNPs was done
      by SNPstream technology (Beckman Coulter SNPstream). All the data of SNPs with
      polymorphism were analyzed by association analysis based on a single SNP, the
      association analysis between phenotypes and SNPs. And pairwise linkage
      disequilibrium was calculated in the control population using Haploview 4.1
      software. RESULTS: SNP1 (rs2073601), SNP2 (rs2073417) and SNP3 (rs2051397) of
      SIM2 are genotyped. SNP2 and SNP3 in linkage disequilibrium. No association (P >
      0.05) is observed between SNP1, SNP2 and SNP3genotypes/allele polymorphisms and
      risk of CS and different clinical phenotypes. CONCLUSION: Genetic variants of
      SIM2 gene may not be associated with the susceptibility to CS and different
      clinical phenotypes of CS in Chinese Han population.

PMID- 20137644
TI  - [A special type of discogenic low back pain: normal signal intensity of magnetic
      resonance imaging with abnormal discography].
AB  - OBJECTIVE: To report a group of special patients showing a normal signal
      intensity of MRI with a positive discography and discuss its pathogenesis and
      clinical significance. METHODS: From August 2003 to November 2008, 288 patients
      with chronic low back pain were treated. Of these patients, 12 showed a normal
      intensity signal of MRI in lumbar intervertebral discs with a positive
      discography. There were 7 males and 5 females aged 20 - 44 years with an average
      of 29.6 years. The duration of disease was 8 months to 3 years with an average of
      1.8 years. Dallas CT grading method was used for assessing the degree of annular
      disruption. RESULTS: Of these 12 patients, 33 lumbar discs underwent discography.
      Twelve discs in 12 patients showed annular disruption and low back pain
      reproduction. Among 12 painful discs, 3 showed grade 2 annular disruption and 9
      showed grade 3 annular disruption. CONCLUSION: Patients who are refractory to
      conservative care and have normal signal intensity in lumbar disc MRI and who are
      suggested as discogenic origin and might need further treatment such as minimal
      invasive surgery or lumbar interbody fusion should still be examined by
      discography.

PMID- 20137645
TI  - [Radical debridement and single stage posterior spinal fusion and instrumentation
      for the treatment of thoracic-lumber tuberculosis].
AB  - OBJECTIVE: To evaluate the radical debridement and single stage posterior spinal
      fusion and instrumentation for the treatment of spinal tuberculosis. METHODS:
      From 1999 to 2004, 57 patients (29 males, 26 females) with spinal tuberculosis
      were operated at our department. The age range was 20 to 77 years old (mean: 39
      years old). There were 30 cases of thoracic vertebra and 27 cases of lumbar
      vertebra. All the patients received a standard pre-operative 4 - 8-week anti
      tuberculosis treatment. RESULTS: The follow-up period ranged from 1 - 4 years and
      95.9% of patients achieved an excellent outcome. Solid bony fusion was seen at
      last in all cases. The mean post-operative kyphosis angle reduced to 20 degrees
      from 32 degrees pre-operation. CONCLUSION: Single stage anterior spinal fusion
      and instrumentation is curative for spinal tuberculosis.

PMID- 20137646
TI  - [A clinical study of viral dynamic change in patients with hepatitis B e antigen
      positive chronic hepatitis B by lamivudine treatment].
AB  - OBJECTIVE: To observe viral dynamic change in patients with HBeAg positive
      chronic hepatitis B by lamivudine treatment. METHODS: A multi-center clinical
      trial. Both outpatients and inpatients with HBeAg positive chronic hepatitis B
      have been administrated lamivudine 100 mg/d for 24 weeks. To detect the hepatitis
      B virus (HBV) deoxyribonucleic acid (DNA) levels of the baseline, 12 hours, 1
      day, 2 days, 3 days, 1 week, 2 weeks, 4 weeks, 12 weeks, 24 weeks after
      lamivudine treatment by real time polymerase chain reaction (PCR). To estimate
      the parameters of viral dynamics through regression analysis. RESULTS: 172
      patients were enrolled, 145 male, 30.8 +/- 9.7 (16 - 65) years old. Significant
      decrease of HBV DNA level occurred 12 hours after administration, the average
      decrease was 0.45 lg(copies/ml), maximum was 3.86 lg(copies/ml), 4 patients
      decreased not less than 2 lg(copies/ml). On day 2 and 7, the average decrease was
      1.20 lg(copies/ml) and 2.01 lg(copies/ml), maximum was 4.41 lg(copies/ml) and
      5.79 lg(copies/ml), respectively. Then HBV DNA level continued decreasing until
      week 24. 24-week administration of lamivudine cause 4.10 lg(copies/ml) decrease
      of HBV DNA averagely and 6.68 lg(copies/ml) mostly. Half life of free virion was
      2.57 days. Half life of infected hepatocyte was 63.0 days. CONCLUSION: Lamivudine
      could rapidly decrease the HBV DNA level of patients with HBeAg positive chronic
      hepatitis B rapidly.

PMID- 20137647
TI  - [Short and long-term outcomes of neoadjuvant chemotherapy for locally advanced
      esophageal carcinoma].
AB  - OBJECTIVE: This study was to compare the 5-year survival rate, the surgical
      resection rate, the post-operative complications and mortality of patients who
      underwent surgical resection for carcinoma of esophagus with or without
      neoadjuvant chemotherapy. To evaluate neoadjuvant chemotherapy in the treatment
      of esophageal carcinoma. METHODS: Forty-two patients with locally advanced
      esophageal carcinoma undergoing neoadjuvant chemotherapy and surgical resection
      (CS group), and 75 patients with the same phase undergoing surgical resection
      alone (S group) from August 2003 to March 2009 in Sun Yat-sen University Cancer
      Center were reviewed. The 5-year survival rate, the surgical resection rate, the
      post-operative complications and mortality between the two groups were analyzed.
      RESULTS: Forty-two patients after neoadjuvant chemotherapy, the complete response
      rate was 11.9%, the partial response was 47.6%, the total clinical response rate
      was 59.5%. The surgical resection rate of CS group and S group were 100% and
      89.5% (P = 0.029). There was no statistically difference in the post-operative
      complications and mortality between two groups. The overall 5-year survival for
      CS group and S group were 31.7% and 26.4%, respectively (P = 0.266). In the
      subgroup analysis, the 5-year survival of patients with clinical response was
      significant higher than S group (P = 0.010). CONCLUSIONS: The neoadjuvant
      chemotherapy can improve surgical resection rate and long-term survival of
      esophageal carcinoma patients with clinical response without increasing the post
      operative complications and mortality.

PMID- 20137648
TI  - [Multimodality interventional treatments for biliary complications after
      orthotopic liver transplantation: a preliminary study].
AB  - OBJECTIVE: To describe the technique, efficacy, and safety of multimodality
      interventional treatments for biliary complications after orthotopic liver
      transplantation (OLT). The core of multimodality interventional treatments is
      percutaneous transhepatic biliary drainage (PTBD). METHODS: From January 2006 to
      May 2008, seventy-two patients with biliary complications afte OLT were closed in
      our study. On the basis of the cholangiographic appearance, patients were
      classified into 4 groups: anastomotic biliary strictures (n = 19), hilar biliary
      strictures (n = 16), multifocal/diffuse biliary strictures (n = 31), and
      anastomotic biliary fistulae (n = 6). All patients were treated in our hospital,
      including PTBD only in 6 patients, PTBD combined with balloon dilation in 50
      patients, balloon dilation and plastic stent implantation in 10 patients, balloon
      dilation and metallic stent implantation in 6 patients. Their data were analyzed
      retrospectively, including serum hemobilirubin, cholangiographic appearance and
      complications. RESULTS: PTBD were successful in all cases. The clinical symptoms
      improved or eliminated were observed in 66 cases, the effective rate was 91.7%
      (66/72). Among 72 patients, 26 patients were free of drainage tube, 8 patients
      underwent second PTBD for the obstruction of biliary stents, and 38 patients
      maintained drainage tube for long-term. In 66 patients with biliary obstruction,
      the direct bilirubin was (145 +/- 106) micromol/L before treatments and 76
      micromol/L +/- 59 micromol/L one month after PTBD (t = 3.78, P < 0.001). The rate
      of biliary tract infection was 14.3% and 43.8% respectively with the tip of
      drainage tube placed in biliary duct and in duodenum. There was a significantly
      statistical difference between these two items (chi(2) = 4.886, P = 0.027).
      CONCLUSION: PTBD combined with balloon dilation and biliary stent implantation is
      a effective therapeutic modality for biliary complications after OLT, which can
      improve patients' clinical symptoms, elevate patients' quality of life. The tip
      of drainage tube being placed in biliary duct can decrease the rate of biliary
      tract infection significantly.

PMID- 20137649
TI  - [Intraarterial neoadjuvant chemotherapy for extremity osteosarcoma].
AB  - OBJECTIVE: To summarize the experiences in intraarterial neoadjuvant chemotherapy
      for extremity osteosarcoma. METHODS: Between January 2002 and December 2007, 111
      patients with stage IIB extremity osteosarcoma received preoperative
      intraarterial chemotherapy after placing chemotherapy pump subcutaneously, en
      bloc resection and postoperative adjuvant chemotherapy. There were 63 males and
      48 females with an average age of 18 years old (range: 14 - 39). The time from
      symptom onset to hospitalization varied from several days to 6 months. The
      induction chemotherapy regimen included epirubicin [50 - 70 mg/m(2) by 4-hour
      intraarterial infusion/day for 3 days] and epirubicin plus adriamycin [100 - 120
      mg/m(2) by 2-hour intraarterial infusion/day for 3 days] repetitively every 2 - 3
      weeks. Among which 24 cases only received 2 cycles of induction chemotherapy was
      assigned into the nonstandard chemotherapy group and 87 cases receiving 3 - 6
      cycles of induction chemotherapy the standard chemotherapy group. The number of
      preoperative chemotherapeutical cycles of standard chemotherapy group depended on
      the clinical and radiographic evaluation of chemotherapy efficacy. RESULTS: The
      median follow-up time was 28 (8 - 48) months. The rate of extremity preservation
      surgery was 89.53% (77/86) in the standard chemotherapy group and 37.5% (9/24) in
      the nonstandard chemotherapy group. Kaplan-Meier survival analysis showed that
      the 3-year overall survival rate and disease-free survival rate of all 111 cases
      were 68.3% and 65.9% respectively. There were significant differences in overall
      survival rate (38.9%, 80.0%, P = 0.000), disease-free survival rate (30.1%,
      79.5%, P = 0.000), distant metastatic rate (66.67%, 16.09%, P = 0.0000) and local
      recurrence rate (58.33%, 13.79%, P = 0.0000) between two groups. CONCLUSION:
      Standard intraarterial neo-adjuvant chemotherapy is more effective than
      nonstandard intraarterial induction chemotherapy to treat stage IIB extremity
      osteosarcoma.

PMID- 20137650
TI  - [Analysis of influence factors of cognitive impairment following first onset of
      stroke].
AB  - OBJECTIVE: To explore the influence factors of cognitive impairment following
      first onset of stroke, in order to predict the existence of cognitive impairment
      in patients with stroke and help for future clinical intervene. METHODS: 364
      survivors of first onset of stroke were evaluated by the mini-mental state
      examination (MMSE) in this study. Data were collected on age, gender, education
      level, location of brain lesion, diagnostic stroke subtype and so on. Logistic
      regressions analyzing is used to determine those factors that could predict
      cognitive impairment of stroke patients by MMSE assessment score. RESULTS: The
      factors including location of brain lesion, area of the lesion, high
      homocysteine, side of the lesion, complications, education level and age can join
      in the logistic regression analysis format. The R of the format is 0.849 and
      these seven factors can explain 72.1% variation of the scores of MMSE.
      CONCLUSION: The logistic regression analysis revealed that location of brain
      lesion, area of the lesion, high homocysteine, side of the lesion, complications,
      education level and age were predictors of the cognition function assessment of
      stroke patients. The prevalence of cognitive impairment can be mainly influenced
      by these factors.

PMID- 20137651
TI  - [The investigations on the relationship between the birth weight of fetus and the
      P70 S6K as well as mechanism insulin regulate the birth weight of fetus].
AB  - OBJECTIVES: To investigate the relationship between the birth weight of fetus and
      the P(70)S6K from ribosome in cells of placental tissues and investigate whether
      insulin can affect the P(70)S6K by the PI3K/AKT/mTOR (P(70)S6K) signaling pathway
      in the cells of the placental tissues and more regulate the birth weight of
      fetus. METHODS: (1) 60 cases of mature placental tissues after uterine-incision
      delivery without complications in the gestational period were selected as the
      investigated subjects, they were divided into three groups according to their
      birth weights. group 1. the weigh of the fetus > or = 4000 g, group 2. 3000 g <
      or = the weight of the fetus < 4000 g, group 3. the weight of the fetus < 3000 g,
      (2) 10 cases of mature placental tissues and 20 cases of villus in the early
      pregnant the fetus that were divided into insulin group, rapamycin group and
      control group according to stimulating factors. investigations on the insulin
      affection activities of P(70)S6K were carried out by immunoprecipitation,
      incorporation of [r-(32)P]ATP, tissue cell culture, Western blotting. RESULTS:
      (1) P(70)S6K activities in mature placental tissues (2546 +/- 357), (2333 +/-
      318), (2111 +/- 315) cpm/mg, there were significant statistical differences in
      the comparison every two groups. (2) The P(70)S6K activities in the placenta from
      the insulin stimulation group was significantly elevated, the P(70)S6K activities
      in the placenta from the rapamycin stimulation group was significantly declined,
      there were statistical significance when each was compared with control group (P
      < 0.01). (3) P(70)S6K activities in the nutrient cells of earlier pregnant period
      and protein expression will be elevated under insulin stimulating. However, that
      would be declined under rapamycin stimulating, it was statistical significant
      when each group compared with the control group (P < 0.01). CONCLUSION: The
      activities of P(70)S6K increased with the increase in the birth weight of the
      fetus, there was certain relationship between the activities of P(70)S6K in the
      placental tissues and the birth weight of the fetus and Insulin can regulate the
      activities of P(70)S6K in the placenta and earlier nutrient cells.

PMID- 20137652
TI  - [Frozen-thawed embryo transfer (FET) versus fresh embryo transfer in clinical
      pregnancy rate during in vitro fertilization-embryo transfer].
AB  - OBJECTIVE: To investigate whether frozen-thawed embryo transfer (FET) instead of
      fresh embryo transfer for the first embryo transfer (ET) in a controlled ovarian
      hyperstimulation (COH) cycle improves the in vitro fertilization-ET clinical
      pregnancy rate. METHODS: The investigators retrospectively analyzed the clinical
      data of 1341 IVF-ET cycles under COH, including 1169 fresh ET cycles (Group T1)
      and 172 FET cycles as the first embryo transfer in COH cycle (Group C1). Logistic
      regression was used to model the probability of clinical pregnancy rate based on
      age, ET method and other cycle-specific factors. RESULTS: The clinical pregnancy
      rate was significantly higher in Group C1 than in Group T1 (63.4% vs 49.4%, P <
      0.01). Multivariate logistic regression analysis revealed significant
      associations between the number of high-quality embryos transferred, patient age
      and ET method in clinical pregnancy rate. After adjusting for the number of high
      quality embryos transferred and age, the clinical pregnancy rate remained
      significantly higher in Group C1 than in Group T1 (odds ratio: 1.75, 95%
      confidence interval: 1.25 - 2.46; P < 0.01). Significant differences were found
      in age (< 35 years old) and the number of retrieved oocytes (> or = 15).
      CONCLUSION: Using FET instead of fresh embryo transfer can improve the clinical
      pregnancy rate and the efficiency of IVF-ET.

PMID- 20137653
TI  - [Complications of hysterectomy: analysis of 162 cases].
AB  - OBJECTIVE: To evaluate the complications of different approaches of hysterectomy
      based on analyzing the records of patients with long post-operative
      hospitalization. METHODS: The records of 3722 patients undergoing hysterectomy
      due to benign gynecologic disorders were retrieved. A total of 162 patients with
      ultra-long post-operative hospitalization (> 9 days defined as delayed discharge)
      were analyzed to evaluate the complications of hysterectomy. RESULTS: (1) Of 162
      patients classified into delayed discharge group, 114 (30.6 per thousand)had post
      operative fever in which 82 cases (71.9%) could be explained with complications.
      (2) The most common procedure-related complications included pelvic
      hematoma/vaginal stump bleeding (n = 46, 12.4 per thousand), wound
      dehiscence/infection (n = 24, 6.4 per thousand), organ injury (n = 20, 5.4 per
      thousand), postoperative urinary retention (n = 20, 5.4 per thousand),
      postoperative infection(n = 20, 5.4 per thousand)and lower extremity deep venous
      thrombosis (n = 10, 2.7 per thousand). (3) Organ injury appeared to be relatively
      more common in abdominal hysterectomy than in laparoscopic and vaginal
      hysterectomy (7.6 per thousand, 2.1 per thousand and 0 respectively) while pelvic
      hematoma/vaginal stump bleeding more common in laparoscopic and vaginal
      hysterectomy than in abdominal hysterectomy (16.5 per thousand, 30.8 per thousand
      and 7.6 per thousand respectively). (4) Wound dehiscence/infection only occurred
      in abdominal approach and it was closely related with some concurrent disorders.
      CONCLUSION: Complications of hysterectomy are related to the approach of surgery,
      disease characteristics and surgeon experiences. A more accurate evaluation of
      complications might be performed on the basis of the data of patients with
      delayed discharge.

PMID- 20137654
TI  - [Clinical analysis of 79 pulmonary arterial hypertension cases from 1892
      connective tissue disease patients].
AB  - OBJECTIVE: To understand the prevalence, investigate the correlation of clinical
      features, explore the early-stage diagnosis and treatment of pulmonary arterial
      hypertension (PAH) in patients with connective tissue disease (CTD). METHODS: All
      cases with pulmonary arterial hypertension in 1892 CTD patients were analyzed
      retrospectively. The risk factor of PAH was evaluated and the prognostic
      influence of different treatments and primary diseases analyzed. RESULTS: The
      prevalence of PAH in patients with connective tissue disease was about
      4.2%(79/1892). In these patients, systemic sclerosis (SSc) and mixed connective
      tissue disease (MCTD) had the highest incidence of PAH (18.18% and 12.00%) (P <
      0.01). It was obviously higher than polymyositis/dermatomyositis (6.2%), systemic
      lupus erythematosus (4.4%), Sjogren syndrome (3.8%), rheumatoid arthritis (0.8%)
      and anti-phospholipid syndrome (0.5%), etc. (P < 0.01). Raynaud's phenomenon was
      related to a higher pulmonary arterial pressure (P < 0.01). There was a positive
      correlation (P < 0.01) between the presence of Raynaud's phenomenon and pulmonary
      arterial pressure. Abnormal lung function was a common finding. There were
      associations (P < 0.05) between the degree of pulmonary hypertension and IgG,
      anti-U1RNP antibody positive, antiphospholipid antibody positive, pericardial
      effusion and interstitial pneumonia. CONCLUSION: PAH is common in connective
      tissue disease. SSc and MCTD have the highest prevalence of PAH. The presence of
      Raynaud's phenomenon anti-U1RNP antibody is positively correlated with pulmonary
      arterial pressure. It can predict the development of PAH. It is useful to perform
      ultraechocardiogrphy for an early-stage diagnosis and prognostic analysis.

PMID- 20137655
TI  - [Controlled release of siRNA nanoparticles loaded in a novel external stent
      prepared by emulsion electrospinning attenuates neointima hyperplasia in vein
      grafts].
AB  - OBJECTIVE: To evaluate a strategy of using TF siRNA loaded in a novel external
      stent prepared by hybrid ultrafine fibrous membrane consisting of PLGA/Chitosan
      nanoparticles as a therapy for vein graft disease. METHODS: Hybrid ultrafine
      fibrous membranes consisting of PLGA/Chitosan nanoparticles were fabricated via a
      specially designed electrospinning setup. After soaking in chloroform to dissolve
      PLGA, the amount of chitosan in the hybrid membranes was determined. The water
      uptake of the hybrid ultrafine fibrous membranes was investigated by incubation
      in phosphate buffer solution. Right jugular vein-carotid artery interposition
      grafting models in Sprague-Dawley rats were randomly divided into five
      groups:Group A (external stent consisting of PLGA/CS-TFsiRNA nanoparticles),
      Group B (external stent consisting of PLGA/CS-Stealth(TM) RNAi negative control
      nanoparticles), Group C (external stent consisting of PLGA/CS blank
      nanoparticles), Group D (external stent consisting of PLGA), Group E (without
      perivenous external stent). BLOCK-iT(TM) Fluorescent Oligo was used to confirm
      its stability and successful transfer into the vein graft wall. The vein grafts
      were harvested at 1, 3, 7, 14, 28 d after operation, respectively. The TF protein
      expression of vein grafts was analyzed by Western blot and immunochemistry at 1,
      3, 7 d after operation, respectively. The expression of proliferating cell
      nuclear antigen (PCNA) was identified by immunochemistry methods. The thickness
      of neointima at 28 d was calculated by computer imaging analysis system. RESULTS:
      The PLGA and CS amount in PLGA/Chitosan nanoparticles membranes could be well
      controlled by adjusting the flow rate for electrospinning of PLGA and chitosan
      nanoparticles, respectively. Because of the introduction of chitosan, which is a
      naturally hydrophilic polymer, the hybrid membranes exhibited good water
      absorption properties. BLOCK-iT(TM) Fluorescent Oligo could be detected in the
      graft wall even 12 days after operation. The expression of TF protein in Group A
      was significantly less than that in control groups at 3 d after operation (P <
      0.05, 0.40 +/- 0.03 vs 0.75 +/- 0.01, 0.75 +/- 0.05, 0.77 +/- 0.07) and at 7 d
      after operation (P < 0.05, 0.30 +/- 0.03 vs 0.84 +/- 0.05, 0.86 +/- 0.06, 0.85 +/
      0.06). The expression of PCNA in Group A decreased significantly in comparison
      with control groups at 14 d after operation (P < 0.01, 13.0% +/- 2.6% vs 25.0% +/
      2.8%, 24.2% +/- 3.9%, 24.0% +/- 4.1%, 44.8% +/- 3.7%). The thickness of
      neointima at 28 d after grafting in Group A was significantly less than the
      untreated group (P < 0.01, 18.8 microm +/- 2.9 microm vs 38.7 microm +/- 5.0
      microm, 37.3 microm +/- 3.6 microm, 37.2 microm +/- 2.6 microm, 67.5 microm +/-
      4.8 microm). CONCLUSION: The novel external stent prepared by hybrid ultrafine
      fibrous membrane consisting of PLGA/Chitosan nanoparticles inhibits early
      neointima formation in rat vein grafts. This strategy may be a practicable and
      promising form of gene delivery against vein graft failure.

PMID- 20137656
TI  - [Protective effects of sevoflurane preconditioning on cerebral ischemia
      reperfusion injury in rats].
AB  - OBJECTIVE: To investigate if sevoflurane preconditioning attenuate neuronal
      apoptosis induced by ischemia-reperfusion. METHODS: Thirty-six male SD rats
      weighing 250 - 300 g were randomly divided into three groups (n = 12 each):
      control group (group C), ischemia-reperfusion group (group IR) (rats were
      established cerebral artery clamped and reperfusion model), sevoflurane
      preconditioning group (group S) (rats were established cerebral artery clamped
      and reperfusion model after 1 h 2.4% sevoflurane preconditioning). Apoptosis
      neurons were observed by Hematoxylin and Eosin (HE) staining and transmission
      electron microscope, TdT mediated Dutp nick end labeling (TUNEL) method was used
      to count apoptosis neurons density, fresh ischemic brain tissue was taken out,
      while Caspase-3 zymogen and 20 000 segment were checked by Western blot. RESULTS:
      apoptosis neurons in group IR were more than ones in group S under HE staining
      and light microscope and transmission electron microscope, and apoptosis neurons
      density (cell number/0.1 mm(2)) by TUNEL staining: group C, 13.0 +/- 1.4; group
      IR, 189.8 +/- 6.8; group S, 110.5 +/- 4.3, the relative gray values of the
      contents of procaspase-3 and its 20 000 cleavage fragment were 16.72 +/- 3.0,
      76.1 +/- 3.4, 51.2 +/- 3.1 and 8.2 +/- 2.3, 59.0 +/- 6.3, 31.2 +/- 5.4
      respectively. CONCLUSIONS: Sevoflurane pretreatment can protect neuron on
      ischemia-reperfusion injury by attenuating neuronal apoptosis in rats.

PMID- 20137657
TI  - [Mechanical properties of therapeutic sand upon femur and its finite element
      analysis].
AB  - OBJECTIVE: To study the mechanical properties of therapeutic sand for femur used
      in the Uygur medicine. METHODS: Rabbits were randomly divided into the treatment
      group and the control group. Rabbits of both groups had arthritis. No treatment
      was carried out for the control group. Only sand therapy was offered for the
      treatment group. After sand therapy was completed, rabbits specimen were removed
      and grouped. The NJ-100B device was employed to measure the femur tensile and
      compressive strength and the analysis of finite element performed upon the
      experimental data. RESULTS: At different sand temperatures below 55 degrees C,
      there was no significant difference in maximal stress and elastic modulus of
      tensile/compressive/bending of each femur sample. CONCLUSION: Under different
      temperatures, the in vitro heating has no obvious effect upon the bio-mechanical
      performance of bone tissues. The static tensile strength of ex vivo femur shows
      no obvious decline. And the compressive strengthen improves somewhat over the
      normal group.

PMID- 20137658
TI  - [Hereditary hearing impairment will face opportunity and challenge from clinic to
      base].

PMID- 20137659
TI  - [The clinical characteristic and risk factors for the incidence of invasive
      fungal infection in patients following allogeneic hematopoietic stem cell
      transplantation].
AB  - OBJECTIVE: To approach the clinical characteristic and risk factors affecting the
      incidence and outcome of post-transplantation invasive fungal infection (IFI) in
      patients with malignant hematologic disease and undergoing allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). METHODS: The incidence and
      outcome of IFI after transplantation in 193 cases of recipients underwent allo
      HSCT in our single center were assessed retrospectively. Some potential
      influential factors for that of IFI were analyzed by methods of bivariate
      correlate analysis and binary logistic regression analysis, including the source
      of donor and stem cell, human leukocyte antigen matched, white blood cell
      engraftment, the history and states of IFI before transplantation, prophylaxis
      schema for GVHD, acute and chronic GVHD. RESULTS: The 2-year cumulative incidence
      of post-transplantation IFI was 34.0% +/- 4.0%. The incidences of breakthrough
      IFI at primary and secondary prophylaxis were 3.8% and 21.1%, respectively (P =
      0.000). 84.2% patients with IFI occurred within half of years after
      transplantation. In fungus that can be measured, molds and yeasts accounted for
      68.1% and 27.7%, respectively. Infective sites in pulmonary or not accounted for
      were 67.3% and 27.7%, respectively. The total effective rate of IFI was 67.3%,
      complete response rate was 44.2%. Furthermore, there was no statistically
      significant difference in the therapeutic effect of antifungal agents between
      patients with a history of IFI and those without before transplantation. IFI
      related mortality was 38.5%. Muti-variate analysis showed acute GVHD was an
      important factor affecting the incidence and outcome of IFI. CONCLUSION:
      Pulmonary mold infection was the most common IFI after allo-HSCT. patients with a
      history of IFI did not seem to be an contraindication for allo-HSCT. Acute GVHD
      was a significant risk factor for the incidence and outcome of IFI.

PMID- 20137660
TI  - [Neural respiratory drive in patients with obstructive sleep apnea].
AB  - OBJECTIVE: To evaluate the variability of neural respiratory drive in patients
      with obstructive sleep apnea (OSA) and the effect of continuous positive airway
      pressure (CPAP) upon neural respiratory drive. METHODS: We recorded diaphragm
      electromyogram (EMGdi) with multi-pair esophageal electrodes and its variability
      during wakefulness, sleep and treatment with CPAP in 13 patients with moderate to
      severe OSA diagnosed by an overnight full polysomnography (OSA group). Six normal
      subjects (control group) were also studied. RESULTS: Coefficient of variation of
      EMGdi (CV-EMGdi) during wakefulness (15.4% +/- 3.8%) was similar to that during
      sleep (17.3% +/- 5.2, P > 0.05) in the control group. The CV-EMGdi during
      wakefulness, sleep, sleep apnea events and treatment with CPAP in OSA group was
      14.7% +/- 1.9%, 40.7% +/- 12.0%, 29.1% +/- 7.5% and 15.4% +/- 4.6% respectively,
      CV-EMGdi during sleep or sleep apnea events was larger than that during
      wakefulness (P < 0.01). However, there was no difference in the CV-EMGdi during
      wakefulness and during treatment with CPAP (P > 0.05). CONCLUSION: The
      variability of neural respiratory drive in patients with OSA is higher than that
      in normal subjects, and CPAP can reduce the variability of neural respiratory
      drive in patients with OSA.

PMID- 20137661
TI  - [Study on mitochondrial function of ND1 gene with 3316 G-->A mutation in human
      diabetes].
AB  - OBJECTIVE: To explore the effects of ND1 gene with 3316 G-->A mutation upon
      mitochondrial function and elucidate its role in the development of human
      diabetes. METHODS: The eukaryotic expression vector pcDNA3.1B and E. coli
      DH5alpha were used to construct the recombinant plasmid (pcDNA3.1B-ND1) of wild
      type and 3316 G-->A mutant type ND1 gene. And the recombinant plasmids were
      analyzed by restriction enzyme digestion and DNA sequencing. Two siRNAs (mtND11
      and mtND12) specific for human mtNDA ND1 gene were designed, synthesized and then
      transfected into Hela cells for silencing endogenous mtDNA ND1 gene. The gene
      silencing effects were analyzed by RT-PCR, SDS-PAGE and MitoCapture mitochondrial
      apoptosis detection kit. Later the two types recombinant plasmids were
      transfected into Hela cells in which endogenous mtDNA ND1 gene was silenced.
      After 48 h culture, the Hela cells were collected for determination of
      mitochondrial proteins by SDS-PAGE. RESULTS: Both mtND11 and mtND12 could
      decrease mtDNA ND1 expression and mtND11 caused a smaller decrease. The
      expression of mitochondrial protein in 3316 G-->A mutant type recombinant
      decreased. CONCLUSION: The normal expression of mitochondrial ND1 gene maintain
      the function of mitochondrial respiratory chain and cell proliferation. The 3316
      G-->A mutation in mitochondrial ND1 gene might be related to the down-regulated
      expression of mitochondrial protein and the diabetes mellitus pathogenesis.

PMID- 20137662
TI  - [Assessment of quality of life in patients with coronary artery disease with
      Seattle angina questionnaire].
AB  - OBJECTIVE: To evaluate quality of life (QOL) of patients with different severity
      of coronary artery disease using Seattle angina questionnaire (SAQ). METHODS: A
      total of 513 hospitalized patients undergoing coronary angiography from December
      2007 to December 2008 were included. QOL of these patients was measured with SAQ
      and their demographic and clinical data were collected. Patients were divided
      into 3 groups according to the severity of coronary artery disease by coronary
      angiography. And comparisons of traditional risk factors and QOL were made among
      these groups. Multiple linear regression analysis was conducted to identify the
      variables associated with QOL. RESULTS: The scores of physical limitation were
      significantly different among 3 groups according to the severity of coronary
      artery disease by coronary angiography (80 +/- 16, 79 +/- 19 and 71 +/- 22, P <
      0.01). Multiple linear regression analysis showed that physical limitation of the
      patients was affected by age (P < 0.01), gender (P < 0.01) and severity of
      coronary artery disease (P < 0.01). Angina stability was affected by the history
      of myocardial infarction (P = 0.03). Angina frequency was affected by the history
      of myocardial infarction (P = 0.01) and gender (P = 0.04). Treatment satisfaction
      was affected by the severity of coronary artery disease (P = 0.03) and disease
      perception by the history of DM (P = 0.03). CONCLUSION: Age, gender, history of
      myocardial infarction, history of DM and severity of coronary artery disease are
      independent predictors of QOL in patients with coronary artery disease.

PMID- 20137663
TI  - [A meta-analysis of effects of high PEEP versus low PEEP upon mortality in
      patients with acute respiratory distress syndrome].
AB  - OBJECTIVE: To evaluate the effects of high PEEP versus low PEEP upon mortality in
      patients with acute respiratory distress syndrome (ARDS). METHODS: The databases
      Medline, Embase, Web of Science, CENTRAL and CBM (Chinese Bio-Medical Literature
      & Retrieval System) were retrieved by using the key words ARDS, ALI, acute
      hypoxemic respiratory failure, acute respiratory distress syndrome, adult
      respiratory distress syndrome, respiratory failure, systemic inflammatory
      response syndrome, non-cardiogenic pulmonary edema, ventilation, PEEP, and
      positive end expiratory pressure, so as to search the materials about the
      randomized controlled trials comparing the mortality of ARDS or ALI treated by
      high PEEP and low PEEP. Study reports were included if they: (1) enrolled over 10
      patients; (2) enrolled adult human ARDS or ALI subjects treated with mechanical
      ventilation; (3) included high PEEP and low PEEP with significant differences;
      and (4) included hospital mortality. RESULTS: Five documents about randomized
      controlled clinical trials, including 2447 patients, met the enrollment criteria.
      The hospital mortalities of high PEEP and low PEEP groups were 34.2% (415/1215)
      and 37.7% (464/1232) respectively (RR = 0.91, 95% CI: 0.82 - 1.01, P = 0.07).
      Sensitive analysis confirmed the nonexistence of differences in hospital
      mortality between these two groups (RR = 0.94, 95% CI: 0.84 - 1.05, P = 0.25).
      Neither funnel plot nor rank correlation test regarding hospital mortality
      indicated the existence of publication bias (chi(2) = 8.26, P = 0.09).
      CONCLUSION: The use of high or low PEEP in oxygenation function does not affect
      hospital mortality in ARDS patients.

PMID- 20137664
TI  - [Value of degree diagnosis with color Doppler flow imaging in the treatment of
      male erectile dysfunction].
AB  - OBJECTIVE: To study the value of degree diagnosis with color Doppler flow imaging
      (CDFI) in the treatment of male erectile dysfunction (ED). METHODS: After CDFI
      and intracavernosal vasoactive agent injection (ICI) with papaverine 60 mg and
      prostaglandin E(1) 10 microg, 198 male ED patients were divided into 4 groups by
      their penile stiffness based on the Schramek criterion. The therapeutic methods
      such as antibiotics for prostatitis, sexual behavior therapy, sildenafil, vacuum
      constriction device (VCD), vena fistula repairing operation, prosthetic
      implantation and enhanced external counterpulsation (EECP) were recommended to
      the patients according to their different penile stiffness degree and their
      different preferences. RESULTS: Prior to ICI, there was no significant difference
      in the cavernosa artery peak systolic velocities (PSV), end diastolic velocities
      (EDV), resistant indexes (RI), dorsal artery PSV, EDV, RI and deep dorsal vein
      velocity (V) (P > 0.05). After ICI, the cavernosa artery PSV, EDV and RI were
      significantly different (P < 0.05) while other indices were not (P > 0.05). The
      patients were treated differently according to their preferences. The selective
      goal-oriented therapy increased the satisfactory rate to 91.91% (182/198).
      CONCLUSION: Based on the penile stiffness degree with CDFI plus ICI, different
      therapeutic methods yield a better clinical outcome.

PMID- 20137665
TI  - [Multiplex ligation-dependent probe amplification analysis of subtelomeric
      chromosome rearrangements in children with idiopathic mental retardation].
AB  - OBJECTIVE: To study the rate of subtelomeric rearrangements in patients with
      idiopathic mental retardation (MR) and to search the cause of MR. METHODS: DNA
      was extracted and purified from peripheral blood leukocytes of 180 patients with
      idiopathic MR. DNA was tested using specific subtelomeric multiplex ligation
      dependent probe amplification (MLPA) kits P036B/C and P070 according to
      manufacturer's instructions. The amplification products were separated by
      capillary electrophoresis using an ABI 3100 automated sequencer and size
      standard. MLPA data were extracted by GeneScan Analysis software. Data
      normalization and analysis were performed with the built-in MLPA application in
      GeneMarker. RESULTS: Among 180 patients with idiopathic MR, 12 had pathological
      subtelomeric deletions including 3 cases with a 4p deletion, 2 cases with a
      deletion at 9q and 22q respectively, 1 case with a deletion at 1p, 7p, 8p, 9q and
      12q respectively. Subtelomeric rearrangements were responsible for 7% cases of
      idiopathic mental retardation. CONCLUSION: Subtelomeric rearrangement is a common
      cause of idiopathic mental retardation.

PMID- 20137666
TI  - [Visfatin promotes production of monocyte chemotactic protein-1 and interleukin-6
      in human endothelial cells via insulin receptor].
AB  - OBJECTIVE: Visfatin is a new novel proinflammatory adipocytokine affecting
      insulin resistance by binding to insulin receptor. To investigate whether
      visfatin stimulates monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL
      6) production in human umbilical vein endothelial cells (HUVEC) and mediates
      insulin receptor (IR) is involved in are not known. METHODS: Cultured HUVEC was
      treated with different doses and durations of visfatin. Furthermore, HUVEC was
      pretreated with hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl
      ester (HNMPA-(AM)3), a specific inhibitor of IR followed by visfatin (100 ng/ml)
      treatment. Enzyme-linked immunosorbent assay (ELISA) were used to measure MCP-1
      and IL-6 production in HUVEC. Real-time quantitative reverse-transcription
      polymerase chain reaction (RT-PCR) was used for determining MCP-1 and IL-6 mRNA
      expression. RESULTS: Visfatin significantly dose- and time- dependently up
      regulated protein production of MCP-1 and IL-6 in HUVEC. We therefore found
      visfatin- induced MCP-1 and IL-6 production and gene expression in HUVEC were
      inhibited by HNMPA-(AM)3. CONCLUSION: Visfatin induces endothelial MCP-1 and IL-6
      production in HUVEC in a dose and time-dependently manner. This action appears to
      be mediated via insulin receptor pathway.

PMID- 20137667
TI  - [Effects of combining siRNA-TR and TERT upon telomerase activity and in vitro
      growth inhibition in transitional cancer of bladder BIU-87 cell line].
AB  - OBJECTIVE: To investigate the influence of combining RNAi-hTR plus hTERT genes
      upon the telomerase activity of bladder cancer BIU-87 cell line and provide new
      methods and evidence for RNAi in gene therapy of bladder transitional cell
      cancer. METHODS: Three hTR-specific double-stranded siRNAs and 3 hTERT-specific
      double-stranded siRNAs were designed targeting different regions of hTR and hTERT
      mRNA. siRNAs (systems-PhTR-siRNA, PhTERT-siRNA and combining systems-PhTR plus
      PhTERT-siRNA) were transfected into bladder transitional cancer BIU-87 cell line.
      And hTR and hTERT mRNA expression were determined by fluorescence quantitative RT
      PCR while telomeric repeat amplification protocol (TRAP) was applied to detect
      the telomerase activity and the growth inhibition of BIU-87 cells detected by MTT
      assay. RESULTS: RNAi-pRNAT-hTERT-III, RNAi-pRNAT-hTR-III and combining RNAi-hTR
      plus hTERT could inhibit the expression of hTERT and hTR mRNA in bladder cancer
      BIU-87 cell lines by RNAi-pRNAT-hTERT-III hTERTmRNA 67%, RNAi-pRNAT-hTR-III
      hTRmRNA 41% and pRNAT-hTR-III hTRmRNA:57%, pRNAT-hTERT-III, pRNAT-hTR-III
      hTERTmRNA:70% (P < 0.05). The growth of bladder cancer BIU-87 cell was inhibited
      and telomerase activity considerably decreased, especially in combining RNAi-hTR
      and hTERT. CONCLUSION: hTR-siRNA, hTERT-siRNA and combing siRNA hTR plus hTERT
      have been successfully designed and constructed. They can suppress specifically
      and effectively both hTR and hTERT mRNA expression and telomerase activity,
      especially in combining siRNA-hTR+hTERT. Combining siRNA-hTR plus hTERT are
      needed to explore its clinical applications.

PMID- 20137668
TI  - [Simultaneous inhibition of both hTERT and androgen receptor gene expression in
      LNCaP cells using single shRNA vector].
AB  - OBJECTIVE: To explore the feasibility of inhibition of hTERT and androgen
      receptor (AR) gene expression simultaneously in LNCaP cells by single shRNA
      vector. METHODS: Templates DNA of both hTERT and AR siRNA were inserted into
      Pgenesil vector to construct a new vector Pgenesil-hTERT-AR-shRNA by RNAi-DNA
      vector technology. Pgenesil-HK-shRNA, Pgenesil-hTERT-shRNA, Pgenesil-AR-shRNA and
      Pgenesil-hTERT-AR-shRNA vectors were transfected into prostate cancer LNCaP cells
      respectively. The levels of AR mRNA, apoptosis and proliferation of each cell
      group were determined by FQ-PCR, Annexin V method and MTT. RESULTS: The level of
      hTERT mRNA of control group cells and cells transfected by Pgenesil-HK-shRNA,
      Pgenesil-hTERT-shRNA, Pgenesil-AR-shRNA and Pgenesil-hTERT-AR-shRNA was (1.51 +/-
      0.08) x 10(8), (7.32 +/- 0.43) x 10(7), (2.94 +/- 0.15) x 10(6), (4.45 +/- 0.25)
      x 10(7) and (3.17 +/- 0.18) x 10(6) (copies/ml) respectively. The level of AR
      mRNA of control cell groups and cells transfected by Pgenesil-HK-shRNA, Pgenesil
      hTERT-shRNA, Pgenesil-AR-shRNA and Pgenesil-hTERT-AR-shRNA was (1.92 +/- 0.11) x
      10(5), (6.47 +/- 0.32) x 10(5), (3.70 +/- 0.24) x 10(4), (1.22 +/- 0.06) x 10(4)
      and (7.21 +/- 0.41) x 10(3) (copies/ml) respectively. These data indicate that
      the expression of hTERT or AR gene could be significantly inhibited by Pgenesil
      hTERT-shRNA or Pgenesil-AR-shRNA while Pgenesil-hTERT-AR-shRNA could
      simultaneously inhibit both hTERT and AR gene expression. The apoptosis rate and
      the inhibition rate of cell growth of Pgenesil-hTERT-AR-shRNA group were
      significantly higher than those of Pgenesil-hTERT-shRNA group or Pgenesil-AR
      shRNA group (P < 0.05). CONCLUSION: It is feasible to inhibit both hTERT and AR
      gene expression simultaneously by single shRNA vector. It will be a new research
      strategy of gene therapy for prostate cancer.

PMID- 20137669
TI  - [Effect of blood glucose control after small intestine exclusion surgery in Goto
      Kakizaki rat with type 2 diabetes mellitus].
AB  - OBJECTIVE: To evaluate the effect of diabetic control after small intestine
      exclusion surgery in Goto-Kakizaki (GK) rat with type 2 diabetes mellitus.
      METHODS: GK type 2 diabetic rats underwent duodenal bypass (Group A, n = 8)
      creating a shortcut for ingested nutrients with bypassing duodenum alone, or
      duodenal-jejunal bypass (Group B, n = 8), a stomach-preserving RYGB excluding
      duodenum and proximal jejunum, or duodenum and total jejunum exclusion (Group C,
      n = 8), or sub-total small intestine exclusion (Group D, n = 8) creating a
      shortcut for ingested nutrients with bypassing duodenum, jejunum and sub-total
      ileum. Controls were pair-fed (PF) sham-operated and untreated GK rats (Group SO,
      n = 8). Rats were observed for 24 weeks after surgery. Fasting blood glucose
      (FBG) level was determined on a Surestep plus blood glucose meter (Lifescan) at
      0, 1, 3, 6, 12, 24 week. Hemoglobin A1c (HbA1c) level was measured at 0, 12, 24
      week on VARIANT Hemoglobin A1c Program (Bio-Ray) with high performance liquid
      chromatography (HPLC) method. RESULTS: The fasting blood glucose and HbA1c levels
      significantly decreased after surgery in all the operative groups through the
      entire follow-up period [Group B (FBG before surgery and 1 week after: (162 +/-
      44) mg/dl vs (80 +/- 19) mg/dl; HbAlc before surgery and 12 week after: (8.2 +/-
      2.2)% vs (5.1 +/- 1.5)%, P < 0.05 or P < 0.01]; while FBG had no differences
      before 12 week and significantly increased at 12 week (164 +/- 44) mg/dl and 24
      week (180 +/- 42) mg/dl in group SO [preoperative (145 +/- 35) mg/dl, P < 0.01].
      As compared with sham-operated rats, all the operative groups showed reduced
      blood-glucose and HbA1c levels through the entire follow-up period (P < 0.05 or P
      < 0.01). The FBG and HbA1c levels in Group B significantly decreased versus Group
      A [24 week (FBG: (82 +/- 21) mg/dl vs (111 +/- 27) mg/dl; HbA1c: (3.9 +/- 0.9)%
      vs (5.4 +/- 1.2)%, P < 0.05], indicating that duodenal-jejunal bypass had
      markedly a better effect of diabetic control. But Groups B, C and D were similar
      to one another (P > 0.05), suggesting that a potential role of proximal gut in
      the pathogenesis of disease. CONCLUSION: In spontaneous type 2 diabetes mellitus
      rats, all the small intestinal exclusion including proximal gut are effective in
      glucose control. In terms of intestinal nutrient absorption, duodenal-jejunal
      bypass may be an ideal surgery for clinical diabetic control. These findings
      suggest a potential role of proximal intestine in pathogenesis of type 2 diabetes
      mellitus.

PMID- 20137670
TI  - [Effects of ANP upon ion pump activity and gene expression in aortic smooth
      muscle cells from spontaneously hypertensive rats].
AB  - OBJECTIVE: To explore the effects of atrial natriuretic peptide (ANP) upon the
      activities of Na(+), K(+)-ATPase, Ca(2+)-ATPase and mRNA expression levels of
      Na(+), K(+)-ATPase alpha(1)-subunit and plasma membrane Ca(2+)-ATPase isoform 1
      (PMCA1) in cultured thoracic aortic vascular smooth muscle cells (ASMCs) isolated
      from spontaneously hypertensive rats (SHR). METHODS: ASMCs isolated from 14-week
      old male SHR and Wistar-Kyoto (WKY) rats were interference-cultured in different
      doses of ANP and Angiotensin II (AngII). The contents of ANP and AngII in
      supernatant from ASMCs were measured by radioimmunoassay. The activities of the
      above two ATPases were measured by biochemistry and enzymology. RT-PCR assay was
      employed to determine the relative levels of Na(+), K(+)-ATPase alpha(1)-subunit
      and PMCA1 mRNA in ASMCs. RESULTS: The ANP level of supernatant in SHR ASMCs was
      significantly lower than those from WKY control [(7.3 +/- 2.4) pg x 10(-6) cells
      vs (19.3 +/- 3.3) pg x 10(-6) cells, P < 0.01] while the content of AngII in SHR
      ASMCs was significantly higher than those from WKY control [(57 +/- 4) pg x 10(
      6) cells vs (44 +/- 4) pg x 10(-6) cells, P < 0.01]. The activity of Na(+), K(+)
      ATPase [(4.3 +/- 0.8) micromol x h(-1) x mg(-1) vs (5.3 +/- 1.0) micromol x h(-1)
      x mg(-1)], Ca(2+)-ATPase [(3.2 +/- 0.7) micromol x h(-1) x mg(-1) vs (4.5 +/-
      0.7) micromol x h(-1) x mg(-1)] in ASMCs from SHR were significantly lower than
      those from WKY control (both P < 0.01). The mRNA expression of Na(+), K(+)-ATPase
      alpha(1)-subunit (0.524 +/- 0.025 vs 0.704 +/- 0.116), PMCA1 (0.193 +/- 0.030 vs
      0.547 +/- 0.045) significantly decreased in ASMCs from SHR versus the WKY control
      (both P < 0.01). As compared with SHR control, exogenous ANP improved obviously
      the activities of Na(+), K(+)-ATPase, Ca(2+)-ATPase and expression of alpha(1)
      subunit, PMCA1 mRNA in a does-dependent manner (P < 0.05-P < 0.01). Exogenous
      AngII (1 x 10(-9), 1 x 10(-8), 1 x 10(-7) mol/L) significantly repressed
      activities of Ca(2+)-ATPase and attenuated the expression of PMCA1 mRNA (P < 0.05
      P < 0.01). Only AngII (1 x 10(-7) mol/L) significantly inhibited the activity of
      Na(+), K(+)-ATPase and attenuated the expression of Na(+), K(+)-ATPase alpha(1)
      subunit mRNA (both P < 0.05). ANP antagonized the effects of AngII (1 x 10(-7)
      mol/L) upon the activities of two ATPases and the expression of Na(+), K(+)
      ATPase alpha(1)-subunit PMCA1 mRNA (P < 0.05-P < 0.01). AngII (1 x 10(-7) mol/L)
      increased the Na(+), K(+)-ATPase activity and the expression of Na(+), K(+)
      ATPase alpha(1)-subunit mRNA, repressed the Ca(2+)-ATPase activity and the
      expression of PMCA1 mRNA in ASMCs from WKY rat (P < 0.05-P < 0.01). ANP
      antagonized the effects of AngII (1 x 10(-7) mol/L) upon the activity of Ca(2+)
      ATPase and the expression of PMCA1 mRNA (P < 0.05-P < 0.01), but did not
      antagonize the effects of AngII (1 x 10(-7) mol/L) upon the activity of Na(+),
      K(+)-ATPase and the expression of alpha(1)-subunit mRNA in ASMCs from WKY rats (P
      > 0.05). CONCLUSION: The decreased activities of Na(+), K(+)-ATPase and Ca(2+)
      ATPase may be related to the abnormal autocrine of ANP and AngII in ASMC of SHR.
      ANP can antagonize the effects of AngII upon the activities of two ATPases and
      the expression of Na(+), K(+)-ATPase alpha(1)-subunit PMCA1 mRNA.

PMID- 20137671
TI  - [Effect of esomeprazole upon intestinal mucosal damage following traumatic brain
      injury in rats].
AB  - OBJECTIVE: To explore the protective effect of esomeprazole upon stress-related
      intestinal mucosal damage following traumatic brain injury (TBI) in rats.
      METHODS: Male Wistar rats were randomly divided into three groups: groups A and B
      served as TBI models and group C was designated as a normal control (shame
      operation). In group B rats were treated subcutaneously with esomeprazole prior
      to TBI while groups A and C rats were treated with an equivalent amount of normal
      saline. During the observation period, the morphological changes of brain tissue
      and intestinal mucosa were observed. And the intestinal mucosal permeability to
      fluorescein isothiocyanate (FITC)-labeled dextran and diamine oxidase (DAO)
      activity were assessed. The activities of superoxide dismutase (SOD),
      myeloperoxidase (MPO) and the levels of malondialdehyde (MDA), reduced
      glutathione (GSH) and hydroxyl radical (OH(*)) were measured. RESULTS: (1) During
      the observation period of TBI, the intestinal mucosal was damaged, but there was
      improvement in group PPI. (2) FITC-dextran leakage increased after TBI and peaked
      at 24 h (P < 0.01); its level of (3720 +/- 401) ng/ml in group PPI was lower than
      that in group TBI (5230 +/- 489) ng/ml (P < 0.05). (3) The DAO activity in mucosa
      decreased and the decline was the greatest at 24 h (P < 0.05), its level of (0.44
      +/- 0.11) ng/ml in group PPI at 24 h was higher than that in group TBI (0.31 +/-
      0.07) ng/ml (P < 0.05); while the DAO activity in serum increased significantly.
      (4) The activity of SOD and the level of GSH in intestinal mucosal started to
      decrease at 3 h and the decline was the greatest at 24 h (P < 0.05), their levels
      were (10.2 +/- 2.8) U/mgprot and (140 +/- 46) mg/gprot respectively in group TBI,
      a remarkable drop in comparison with those of PPI group (13.0 +/- 2.4) U/mgprot
      and (208 +/- 48) U/gprot (P < 0.05). (5) The levels of OH(.), MDA and MPO in
      intestinal mucosal increased and peaked at 24 h (P < 0.05), the respective levels
      in group PPI (108 +/- 8), (6.2 +/- 0.6) and (1.53 +/- 0.52) U/mgprot and those in
      the TBI group (150 +/- 8), (7.7 +/- 0.9), (1.93 +/- 0.53) U/mgprot, demonstrated
      that there was a remarkable rise (P < 0.05). CONCLUSION: Traumatic brain injury
      may lead to stress-related intestinal mucosal damage. Oxygen free radicals play
      an important role in intestinal mucosal barrier damage. Esomeprazole attenuates
      the damage of intestinal mucosal barrier by antioxidant effect and inhibiting the
      activity of neutrophil.

PMID- 20137673
TI  - [More attention should be paid to skeletal lesions of Gaucher disease].

PMID- 20137672
TI  - [Consensus, controversies and evidence-based research in future of polycystic
      ovary syndrome].

PMID- 20137674
TI  - [Effect of hyperprolactinemia upon clinical symptoms of patients with polycystic
      ovary syndrome].
AB  - OBJECTIVE: To determine the effects of hyperprolactinemia (hyperPRL) upon the
      symptoms of patients with polycystic ovary syndrome (PCOS). METHODS: Age, body
      mass index, levels of hormone, lipid, beta-cell function and family medical
      history of 224 women with PCOS and 30 women with hyperPRL + PCOS were compared.
      RESULTS: Patients with hyperPRL + PCOS were younger to develop endocrine
      disturbances, an increased incidence of acne (64% vs 28% respectively), a high
      level of androstenedione (20 + or - 7 vs 13 + or - 5) nmol/L respectively and
      prolactine in serum (1492 + or - 1175 vs 367 + or - 164) mIU/L respectively; The
      PCOS patients were divided into the groups of hyperandrogenism PCOS and non
      hyperandrogenism PCOS depending on the serum level of androgen. A higher level of
      T and A was found in serum in PRL-PCOS than non-hyperandrogenism patients and
      similar as hyperandrogenism PCOS patients. They had reduced ApoB (680 + or - 230
      nmol/L vs 943 + or - 179 mmol/L respectively) and Lpa level (46 + or - 22 nmol/L
      vs 162 + or - 194 mmol/L respectively) and high HOMA-IR when compared with non
      hyperandrogenism PCOS; Patients' sisters with hyperPRL + PCOS had a significantly
      greater incidence of acne, higher rates of infertility and PCOS when compared
      with PCOS patients. Levels of other hormones, metabolic profiles and other family
      histories did not differ between patients with PCOS and hyper-PRL+PCOS.
      CONCLUSION: Patients with hyperPRL + PCOS develop the endocrine disturbances at a
      younger age, a greater incidence rate of acne, level of prolactin and
      androstenedione, they have reduced ApoB and increased HOMA-IR. Patients' sisters
      with hyperPRL + PCOS have significantly greater incidence of acne, higher rates
      of infertility and PCOS as when compared with PCOS patients.

PMID- 20137675
TI  - [Different types of menstrual cycle and their significance in Chinese women
      diagnosed with polycystic ovary syndrome according to the Rotterdam consensus
      criteria].
AB  - OBJECTIVE: To analyze the clinical and metabolic characteristics of Chinese women
      with different menstrual types. All the women were diagnosed with polycystic
      ovary syndrome according to the Rotterdam consensus criteria. METHODS: A total of
      2100 patients were divided into three groups: amenorrhea, oligomenorrhea and
      regular menstruation. The metabolism and endocrine indices were determined and
      compared among three groups. RESULTS: (1) The incidences of hirsutism and PCO
      were obviously higher in the amenorrhea group than in the oligomenorrhea group (P
      < 0.01). (2) The amenorrhea group had the highest level of serum testosterone
      while the oligomenorrhea group had the lowest. Moreover, the level of luteinizing
      hormone (LH) was higher in the amenorrhea group than in the other two groups (P <
      0.01). However the ratio of LH/FSH increased significantly in the regular
      menstruation group (P < 0.01). (3) The value of 2 h blood glucose was the highest
      in the amenorrhea group (P < 0.01). CONCLUSION: PCOS patients with diverse types
      of menstrual cycle show different clinical manifestations and metabolic and
      endocrine characteristics so that the choice of treatment should be
      individualized.

PMID- 20137676
TI  - [Correlations between adipocytokines and insulin resistance in women with
      polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate the correlations between adipocytokines and insulin
      resistance in women with polycystic ovary syndrome. METHODS: Sixty women with
      polycystic ovary syndrome aged 19-34 years old were divided into 2 groups: group
      A [n = 36, BMI > or = 25 kg/m(-2) or WHR (waist height ratio) > 0.85] and group B
      (n = 24, BMI < 25 kg/m(-2) and WHR < or = 0.85). Twenty-six healthy infertile
      women with a mean age of 26 + or - 8 years old served as controls and they were
      named as group C (n = 26, BMI < 25 kg/m(-2) and WHR < or = 0.85). Anthropometric
      measurements, hormonal profiles and metabolic profiles were compared between
      three groups. Plasma leptin, CRP and free fatty acid were measured by enzyme
      linked immunosorbent assay (ELISA). Adiponectin, interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) were measured by radioimmunoassay. Insulin
      resistance was estimated by homeostasis model assessment (HOMA). RESULTS: (1)
      Adiponectin and TNF-alpha levels were significantly higher in group B (17 + or -
      9) mg/L and (1.0 + or - 0.3) mg/L respectively than in group A (10 + or - 7) mg/L
      and (0.8 + or - 0.2) mg/L respectively. Leptin was lower in group B (24 + or -
      13) microg/L and group C than in group A (42 + or - 21) microg/L (all P < 0.01).
      IL-6 was higher in group A (173 + or - 184) ng/L and group B (184 + or - 44) ng/L
      than in group C (P < 0.05 and P < 0.01 respectively). No significant difference
      of circulating level of CRP was found between these 3 groups. (2) Leptin was
      positively correlated with BMI, WHR and HOMA-IR (all P < 0.01) whereas
      adiponectin was negatively correlated with BMI, WHR and HOMA-IR (P < 0.01; P <
      0.01, P < 0.05 respectively). Multivariate regression showed that adiponectin was
      the most significant predictor of HOMA-IR and it explained 16.5% of variance.
      CONCLUSION: The higher levels of leptin and TNF-alpha, the lower level of
      adiponectin in obese PCOS and the higher level of TNF-alpha and IL-6 in non-obese
      PCOS suggested different adipocytokines play different roles of insulin
      resistance in PCOS.

PMID- 20137677
TI  - [Insulin resistance enhanced the response of the ovary].
AB  - OBJECTIVE: To search for the role of impaired insulin signaling in the ovary
      reproductive failure and abnormal metabolic profiles in the AKT2- mouse. METHODS:
      Adult, female 129/C57BL/6 (AKT2-) mice were used in these studies. Littermate
      wide types C57BL/6J (AKT2+), as well as mutant genotypes (AKT2-). The ovaries
      were abstained from 6 AKT2+ type mice as wall as 6 mutant genotypes, which was
      used for insulin stimulated glucose uptake study. By ovary transplantation on the
      day of 12 weeks, three genotypic mice were constructed with body AKT2+ and ovary
      AKT2+ in Group A, body AKT2+ and ovary AKT2- in Group B, body AKT2- and ovary
      AKT2+ in Group C. The vaginal smear was done to evaluate the recovery and
      cyclicity of transplanted ovaries with mutant or intact AKT2. Before execution,
      every group was randomly separated into basal and stimulated groups in which the
      mice were injected recombination FSH (0.75 IU/g), and then AKT2, GSK3beta, ERK-1,
      CYP17 and CYP19 were determined by RT-PCR in the ovaries, and the serum were
      reserved for the assay of HDL-C, CHO, TG, 17-OHP progesterone, E(2), T, and LH.
      The weight of each mouse, their ovary and their fat pads and the estrus cycle,
      were also recorded. RESULTS: (1) The weight of fat pads beside ovaries and fold
      inguen in C group were significant higher than the other groups. (2) The level of
      17-OHP progesterone in B group was higher than A or C group both in basal and FSH
      stimulated groups. (3) In the basal group the expression of ERK-1 and CYP17 were
      enhanced. Moreover in FSH-d stimulated group, the expression of ERK-1, CYP17,
      CYP19 and GSK3B in B group were higher as compared with the other groups.
      CONCLUSION: (1) IR existed in the ovary of AKT2- type, and the mice with AKT2
      type ovary had delayed cycle, PCO and high level of 17-OHP, which were similar
      with PCOS. (2) Metabolic dysfunction in the AKT2- mice has close relationship
      with whole body condition, but not defective insulin signal within ovaries. (3)
      Defects of insulin activity in the metabolic pathway could induce the increased
      expression of ERK-1 and mitogenic potential indicating the cross-talk between two
      pathways of insulin signaling within ovarian cells. Consequently, ovarian
      hyperovarianism was induced in the defective ovaries, which contribute to the
      enhanced response to gonadotropin and synthesis of steroid hormone.

PMID- 20137678
TI  - [Sensory gating P50 in schizophrenic patients with and without homicide].
AB  - OBJECTIVE: To investigate the change of sensory gating P50 in schizophrenic
      patients with and without homicide. METHODS: The auditory evoked potentials P50
      were recorded from 26 schizophrenic patients with homicide (Sch group), 27
      schizophrenic patients without homicide (non-Sch group) and 32 normal controls
      (NC) using conditioning/testing paradigm presented with auditory double click
      stimuli by EGI 256 dense array. And the same time, their clinical symptoms were
      evaluated by positive and negative symptom scale (PANSS). RESULTS: (1) Compared
      with NC, two Sch groups showed no significant difference in amplitude and latency
      of S1-P50 [amplitude: NC, Sch group, non-Sch group at Fz: (2.4 + or - 1.6)
      microV, (2.5 + or - 1.5) microV, (3.4 + or - 2.7) microV; latency: NC, Sch group,
      non-Sch group at Fz: (68 + or - 19) ms, (67 + or - 20) ms, (61 + or - 19) ms;
      respectively], but a higher amplitude and delayed latency of S2-P50 [amplitude:
      NC, Sch group, non-Sch group at Fz: (0.8 + or - 0.7) microV, (2.5 + or - 1.6)
      microV, (3.3 + or - 2.2) microV; latency: NC, Sch group, non-Sch group at Fz: (50
      + or - 26) ms, (75 + or - 19) ms and (70 + or - 24) ms respectively] (P < 0.01),
      and no significant difference in amplitude and latency of S2-P50 between two Sch
      groups. (2) Compared with NC, two Sch groups showed a higher S2/S1 ratio [NC, Sch
      group, non-Sch group at Fz: 35 + or - 26, 153 + or - 137, 125 + or - 85,
      respectively], lower S2-S1 [NC, Sch group, non Sch group at Fz: 1.69 + or - 1.55,
      0.08 + or - 2.41 and 0.17 + or - 2.30, respectively] and 100 (1-S2/S1) [NC, Sch
      group, non-Sch group at Fz: 65 + or - 26, -53 + or - 137 and -25 + or - 85
      respectively] (P < 0.01). And there was no significant difference in S2/S1 ratio,
      S2-S1 and 100 (1-S2/S1) between two Sch groups. (3) Two Sch groups showed no
      significant difference in PANSS total, P scale, N scale, and G scale [Sch group:
      (110 + or - 27), (26 + or - 10), (29 + or - 7), (55 + or - 12); non Sch group:
      (105 + or - 27), (24 + or - 8), (28 + or - 10) and (53 + or - 12) respectively]
      (P > 0.05), and no significant correlation with S2/S1 ratio, S2-S1 and 100(1
      S2/S1) (P > 0.05). CONCLUSION: Sensory gating deficit exists in schizophrenic
      patients with and without homicide. And it can be quantified by measuring
      auditory evoked potential P50, but sensory gating P50 has no difference between
      schizophrenic patients with and without homicide.

PMID- 20137679
TI  - [Comparison of correction outcomes after anterior or posterior approach with
      lowest and vertebra instrumentation in adolescent idiopathic thoracolumbar/lumbar
      scoliosis].
AB  - OBJECTIVE: To evaluate the different influences upon the correction outcomes
      after anterior or posterior correction and fusion with lowest end vertebra
      instrumentation in adolescent idiopathic thoracolumbar/lumbar scoliosis. METHODS:
      By reviewing the medical records and roentgenograms of adolescent idiopathic
      thoracolumbar/lumbar scoliosis patients undergoing anterior (single rod-Group A)
      or posterior (all pedicle screws-Group B) correction and instrumentation, the
      parameters of Cobb angle of the curve, correction rate and disc angle were
      measured and analyzed. RESULTS: There were 18 patients in Group A and 21 patients
      in Group B. The curve included 5.0 vertebrae and 5.5 vertebrae (P = 0.134)
      respectively, and the fusion levels were 4.7 vertebrae and 5.4 vertebrae (P =
      0.008) respectively. The mean pre-operative and post-operative coronal Cobb
      angles of the main curve in Groups A and B were 49.2 degrees and 10.3 degrees ,
      42.2 degrees and 5.0 degrees with an average correction rate of 78.5% and 87.8%
      respectively. The Cobb angles were all significantly corrected (all P = 0.000),
      and group B had a better correction result (P = 0.020). At final follow-up, the
      coronal Cobb angles in the two groups were 21.7 degrees and 7.7 degrees with an
      average correction loss of 8.3 degrees and 2.7 degrees (P = 0.001) respectively.
      The disc angles at pre-operation, post-operation and final follow-up were 3.1
      degrees , 5.6 degrees and 7.3 degrees in Group A and 2.3 degrees , 4.2 degrees
      and 4.4 degrees in Group B respectively. The disc angle at post-operation was
      larger than that at pre-operation and the difference was significant in Group A
      (P = 0.049) while not in Group B (P = 0.050). The difference of post-operative
      disc angle between two groups was not significant (P = 0.231). At final follow
      up, the disc angle was a little larger than that of post-operation without a
      significant difference (P = 0.112, P = 0.855) while Group A had a larger disc
      angle (P = 0.026). At final follow-up, the occurrence of proximal junctional
      kyphosis between Groups A and B was not significant (P = 0.235). CONCLUSION: For
      adolescent idiopathic thoracolumbar/lumbar scoliosis, in comparison with the
      anterior approach, the posterior approach using all pedicle screws can achieve a
      better correction outcome, a less correction loss of coronal Cobb angle and a
      better disc angle with a longer fusion range.

PMID- 20137680
TI  - [Comparison of multiple pregnancy rate following transfer of frozen-thawed or
      fresh embryos and analysis of related factors].
AB  - OBJECTIVE: To compare the multiple pregnancy rates of frozen-thawed embryos
      transfer (FET) or fresh embryos transfer, analyze the factors related to multiple
      pregnancies after IVF and study pregnancy rates with different number of embryos
      transferred in FET cycle. METHODS: A retrospective analysis was performed upon
      multiple pregnancies from 1235 and 1561 clinical pregnancies conceived by FET or
      fresh embryo transfers. RESULTS: No correlation was found between fresh or
      cryopreserved embryos transfer and multiple pregnancy rates. There were
      significant effects of woman's age, number of embryos transferred and stage of
      embryos upon multiple pregnancy rates. When the same number of cleavage-stage
      embryos was transferred to women with the same age, twin pregnancy rate or
      triplet pregnancy rate was the same between FET and fresh cycles. Triplet
      pregnancy rate with three embryos transferred was significantly higher than that
      of two embryos transferred. In women under 35 years old, the pregnancy rate with
      two embryos transferred reached 36.1%. CONCLUSION: Frozen-thawed embryos or fresh
      embryos transfer has no effect upon the multiple pregnancy rate. Women under 35
      years old can achieve acceptable pregnancy rates when two cryopreserved embryos
      are transferred. It is helpful to reduce the triplet pregnancy rate.

PMID- 20137681
TI  - [Treatment for osteonecrosis of femoral head by hVEGF-165 gene modified marrow
      stromal stem cells under arthroscope].
AB  - OBJECTIVE: To understand the biological characteristics and osteogenic potential
      of hVEGF-165 gene modified marrow stromal stem cells and investigate the effect
      and value of treatment for osteonecrosis of femoral head by hVEGF-165 gene
      modified marrow stromal stem cells under arthroscope. METHODS: rAAV-2-hVEGF-165
      plasmids were extracted and transfected into rabbit marrow stromal stem cells.
      hVEGF-165 mediated by adeno-associated virus (AAV) was used to transfect rMSCs.
      The transfection efficiency was detected with enhanced green fluorescent protein
      under fluorescence microscope. hVEGF-165 mediated by adeno-associated virus (AAV)
      was used to transfect rMSCs. Virus transfection stayed overnight after 90% cell
      converged. MOI was 105. The transcription and expression of hVEGF-165 protein
      expression were detected by RT-PCR and Western blot. The necrotic bone was
      emptied and then MSCs were implanted under arthroscope. The histology of femoral
      head was inspected at postoperative 2 - 8 weeks. RESULTS: The expression of hVEGF
      165 gene could be found distinctly in the transfected rabbit MSCs and hVEGF-165
      protein in the supernatants of transfected cell cultures. The transfection
      efficiency of adeno-associated virus (AAV) transfected rMSCs was 70%. And rAAV-2
      hVEGF-165 transfected rMSCs achieved an effective expression by RT-PCR and
      Western blot. hVEGF-165 could be found after a 48-hour transfection and peaked at
      Day 10. Immunohistochemical detection showed that the implanted rMSCs was
      positive at Week 2 and strong positive at Week 8. The compressive strength of the
      hVEGF-165 gene group approached that of normal control. CONCLUSION: hVEGF-165
      gene transfected rabbit MSCs can express hVEGF-165 with highly biological
      activity. It provides provided a basis for employing hVEGF-165 gene and MSCs
      based gene therapy for ONFH repairing and regeneration. rAAV-2-hVEGF-165/MSCs may
      be implanted accurately under arthroscope. Implantation of human BMP-2 gene
      transfected BMSCs can repair early-stage experimental femoral head necrosis.

PMID- 20137682
TI  - [Brain injury in adenosine A1 receptor knock-out mice after pentetrazole kindling
      and its correlation with COX-2].
AB  - OBJECTIVE: To investigate the brain injury of neurocytes in hippocampus of
      adenosine A1 receptor knock-out mice during pentetrazole kindling and detect the
      correlation of brain injury and the expression of COX-2 so as to evaluate the
      neuroprotective function of adenosine A1 receptor and its mechanism. METHODS: The
      animals were divided into two groups: wild type group and KO group. The kindling
      model was established by injection of pentetrazole into abdominal cavity. The
      expression of brain injury related protein, caspase-3 and COX-2 in hippocampus
      was investigated separately at different time points (24 hour, 1 month) post
      kindling. RESULTS: The expression of Caspase-3 and COX-2 increased in KO group
      both during acute and chronic phases post-kindling compared with normal mice.
      There was statistical difference (P < 0.05). Furthermore, the expression levels
      of two proteins were higher at 1 month compared with 24 hour (P < 0.01). These
      results indicated that the increased expression of Caspase-3 and COX-2 post
      kindling was earlier and much more in KO mice as compared with wild-type ones.
      CONCLUSION: Adenosine exerts strong neuroprotective functions through the
      activation of adenosine A1 receptor. This receptor reduces cell apoptosis during
      pentetrazole kindling. Cyclooxygenase-2 (COX-2) reflects the extent of brain
      injury. The neuroprotective function mediated by adenosine A1 receptor might be
      related with COX-2.

PMID- 20137683
TI  - [Small interfering RNA (siRNA) targeting vascular endothelial growth factor
      inhibits vascular leakage in brain of rats exposed to high altitude].
AB  - OBJECTIVE: To observe the change of expression of vascular endothelial growth
      factor (VEGF) and vascular leakage in the brain of rats exposed to high altitude
      with siRNA targeting vascular endothelial growth factor and explore the
      pathological mechanism and preventive approach of high altitude cerebral edema
      (HACE). METHODS: Fifty male Wistar rats were divided randomly into normal control
      group (Ncon), high altitude control group (Hcon), intraventricular normal saline
      control group (Scon), intraventricular siRNA group (CVI) and intravenous siRNA
      group (IVI). Rats in Ncon were raised normally. Rats in Hcon, Scon, CVI and IVI
      pretreated with intravenous injection of normal saline, intraventricular
      injection of normal saline, intraventricular injection of siRNA and intravenous
      injection of siRNA respectively were exposed to a low-pressure cabin mimicking a
      high altitude of 7000 m for 24 h. The ratio of dry and wet brain weight was
      calculated and the sodium fluorescein leakage calculated to evaluate the cerebral
      edema and the blood brain barrier permeability. Also the real-time quantitative
      RT-PCR was employed to detect the expression of VEGF mRNA and the Western blot
      the expression of VEGF. RESULTS: Compared with rats in NC, high altitude exposure
      led to a significant increase in the levels of VEGF mRNA (from 21.6 + or - 3.5 K
      copies/microg to 36.3 + or - 3.9 K copies/microg, P < 0.01) and protein (from 48
      + or - 0.09 to 0.77 + or - 0.12, P < 0.01) in rat brain and fluorescence
      intensity of sodium fluorescein increased significantly (from 548 + or - 48
      rfu/mg to 674 + or - 32 rfu/mg, P < 0.01). Intravenous injection of siRNA
      targeting to VEGF caused no significant change of expression VEGF mRNA and
      protein and fluorescence intensity of sodium fluorescein in rat brain (P > 0.05,
      respectively). While compared with rats in HC, intraventricular injection of
      siRNA targeting to VEGF caused the significant reduction of expression of VEGF
      mRNA (from 36.3 + or - 3.9 to 19.9 + or - 4.3, P < 0.01) and protein (from 0.77 +
      or - 0.12 to 0.44 + or - 0.13, P < 0.01) and fluorescence intensity of sodium
      fluorescein (from 674 + or - 32 rfu/mg to 542 + or - 77 rfu/mg, P < 0.05) in rat
      brain. There were no significant change in the ratio of dry and wet brain weight
      among five groups. CONCLUSION: VEGF may play a key role in the pathologic process
      of HACE. Intraventricular injection of siRNA targeting to VEGF inhibits the
      expression of VEGF and prevent the high altitude-induced vascular leakage. These
      findings might provide a basis for new preventive approaches of cerebral edema.

PMID- 20137684
TI  - [Treatment of osteosarcoma with TNF-related apoptosis-inducing ligand or in
      combination with doxorubicin in animal experiment].
AB  - OBJECTIVE: To examine the effect of TNF-related apoptosis-inducing ligand (TRAIL)
      and in combination with doxorubicin (ADM) to xenografted tumors in nude mice and
      to explore its potential mechanism. METHODS: MG-63 cells (5 x 10(6)/ml) were
      suspended in 0.2 ml RPMI-1640 and inoculated subcutaneously into the lower limb
      of nude mice. Treatment groups were given TRAIL of different concentration or
      combination of TRAIL and ADM intraperitoneally. Normal saline was administrated
      in the control group. Anti-tumor effects were estimated by tumor volumes. Serum
      alkaline phosphatase (ALP) was detected by ALP kits. Induction of apoptosis in
      xenografted tumors was confirmed by TUNEL (TdT-mediated dUTP nick end labeling)
      assay. Expression of Bax was detected by immunohistochemical assay. Expression of
      TRAIL receptors was detected by RT-PCR assay. RESULTS: Growth curve of tumors
      indicated that tumors carried by TRAIL-treated mice grew more slowly than that
      with normal saline and 2 microg TRAIL was more effective, Also tumors treated
      with combination of TRAIL and ADM grew more slowly than any other group. ALP
      activities of each group were moderately different but significance was not
      reached. TUNEL showed that there were more apoptotic cells in the combination
      group than any other group. Immunohistochemical assay showed that expression of
      Bax was up-regulated in the combination group. RT-PCR showed that expression of
      TRAIL-R2 mRNA was up-regulated in the combination group. CONCLUSION: TRAIL can
      induce an effective apoptosis of osteosarcoma cells in vivo in a dose-dependent
      fashion. ADM can enhance the effect of TRAIL-mediated apoptosis. And up
      regulations of Bax and TRAIL-R2 may be the involved mechanism.

PMID- 20137685
TI  - [Hepatitis C virus NS3/4A with different secondary structures at amino-terminus
      has different serine protease activities and inhibitory activities on host cell].
AB  - OBJECTIVE: To construct the point mutation plasmids expressing NS3/4A with
      different secondary structure of the amino-terminal 120 residues of NS3, and to
      investigate the differences in serine protease and inhibitory effects on host
      cells between each subgroup. METHODS: The point mutation plasmids were
      constructed, which expressed NS3/4A with the corresponding secondary structures
      of subgroup, and were named as A1-2, A2-1, A2-2, B1-1, B1-2, B2-1, and B2-2, with
      the backbone of M-H05-5 (A1-1). Western blot was performed to detect the
      expression of NS3/4A and the difference in in cis and in trans NS3 serine
      protease activity between each subgroup. The inhibitory effects of HCV NS3/4A
      with different amino-terminal secondary structures on IFN-beta production and p53
      dependent transcriptional activation were revealed by Luciferase reporter assay.
      RESULTS: Western blot revealed the successful expression of the constructs and
      the incomplete cleavage of NS3/4A in subgroup A2-1 and B2-1, indicating that the
      in cis NS3 serine protease activities of subgroup A2-1 and B2-1 were weaker
      compared with that of the other subgroups. By using NS5A/5BDeltaC as a substrate
      for NS3/4A serine protease, it was also found that the in trans NS3 serine
      protease activities of subgroup A2-1 and B2-1 were also weaker compared with that
      of the other subgroups. Differences in inhibitory effects of HCV NS3 on IFN-beta
      promoter activity and on p53-dependent luciferase gene transcriptional activation
      were also observed between subgroup A2-1, B2-1 and the other subgroups.
      CONCLUSION: HCV NS3/4A with different secondary structures at amino-terminus has
      different serine protease activities and inhibitory activities on host cell
      functions.

PMID- 20137686
TI  - [Experimental study of the effect of radiofrequency ablation with series of WHK-3
      conformable electrode in ex vivo ox liver].
AB  - OBJECTIVE: To evaluate the conformablity and quantization controllability of
      multi-cluster conformable radiofrequency ablation electrode by ex vivo animal
      experiment. METHODS: The subject using in this experiment were fresh ex vivo ox
      liver. The electrode we used were the series of WHK-3 (including WHK-3 I and II),
      which were design and made by Welfare Electronic Technological Company (Beijing).
      Each electrode had 6 sub-electrode on opposite side (A and B). Both A and B side
      could separately in different length and radian so to form asymmetric shape. The
      difference between WHK-3 I and II were the shaft of I are electric conductive
      while it of WHK-3 II were inconductive by coating with insulant material. Our
      subject were divide into 3 group. In group 1 we do radiofrequency ablation in ex
      vivo ox liver with both sub-electrode (WHK-3 I and II) fully spread out
      symmetrically, then the diameter of 3D cross section in zone of melt necrosis
      between type I and II were compared. In group 2 we do radiofrequency ablation in
      ex vivo ox liver with WHK-3 I while the two side of sub-electrode were spread out
      asymmetrically in different shapes. Then the diameter of cross section which were
      parallel to the electrode shaft in zone of melt necrosis in different sub
      electrode shape were compared. In group 3 we do the test same way as in group 2
      on WHK-3 II electrode. RESULTS: In group 1, there had no significant different
      between the diameter of melt necrosis zone in ex vivo ox liver with WHK-3 I and
      II (average around 6 x 6 x 3 cm(3)) while sub-electrodes were fully spread out
      symmetrically. In group 2, while sub-electrode in A side were fully spread and
      sub-electrode in B side were half spread, WHK-3 I electrode could form an
      asymmetric melt necrosis zone. The diameter on A side were 3.24 + or - 0.32 cm
      and it on B side were 1.87 + or - 0.24 cm. While only A side sub-electrode were
      spread out, the diameter on A side were nearly the same and it on B side were
      decreased to 1.55 + or - 0.16 cm. In group 3, while sub-electrode in A side were
      fully spread and sub-electrode in B side were half spread, WHK-3 II electrode
      could form an asymmetric melt necrosis zone too. The diameter on A side were 3.27
      + or - 0.35 cm and it on B side were 1.65 + or - 0.23 cm. While only A side sub
      electrode were spread out, the diameter on A side were nearly the same and it on
      B side were decreased even to 0.90 + or - 0.18 cm. CONCLUSIONS: The series of WHK
      3 could form an asymmetric melt necrosis zone in ex vivo tissue, which were more
      suitable to clinical usage. And both of them had quantization controllability,
      especially in WHK-3 II.

PMID- 20137687
TI  - [Effect of estrogen-depletion and 17beta-estradiol replacement therapy upon rat
      hippocampus beta-amyloid generation].
AB  - OBJECTIVE: To observe the effects of estrogen depletion and 17beta-estradiol
      replacement therapy upon ratbeta-amyloid (Abeta) generation and the possible
      related mechanisms. METHODS: Rat ovaries were ectomized to mimic estrogen
      depletion models and then 17beta-estradiol was administered by powdering hormone
      into soy-free chow as a way of replacement therapy. ELISA was carried out to
      detect rat hippocampus Abeta levels and alpha- and beta-secretase activities were
      measured after the experiment. The effects of estrogen depletion and 17beta
      estradiol replacement therapy upon beta-secretase (BACE1) and neprilysin (NEP)
      expression were also analyzed by Western blot. RESULTS: Ovariectomy significantly
      decreased estrogen level [(11 + or - 4) pg/ml, P < 0.01] as compared with control
      group [(21 + or - 8) pg/ml] while 17beta-estradiol administration increased the
      estrogen level [(63 + or - 13) pg/ml, P < 0.01] in blood. The Abeta40 [(28.5 + or
      - 4.5) ng/ml, P < 0.01] and Abeta42 [(4.5 + or - 1.2) ng/ml, P < 0.01] levels
      were higher in ovariectomy group as compared with their respective control group
      [with Abeta40 (14.4 + or - 2.4) ng/ml and Abeta42 (2.8 + or - 0.4) ng/ml
      respectively]. But the effects of ovariectomy on Abeta content can be partially
      reversed by 17beta-estradiol replacement therapy [with Abeta40 (20.3 + or -
      3.2)ng/ml, P < 0.01 and Abeta42 (3.8 + or - 0.5)ng/ml, P < 0.01 respectively].
      Estrogen depletion decreased alpha-secretase activity (67.5%, P < 0.01) and
      increased beta-secretase activity (145.8%, P < 0.01) and this effect can be
      blocked by 17beta-estradiol administration [with alpha-secretase activity to
      90.2% (P < 0.01) and beta-secretase activity to 92.4% (P < 0.01)]. Ovariectomy
      increased BACE1 expression (135.4%, P < 0.01) and decreased NEP expression
      (40.8%, P < 0.01) and this effect can be partially antagonized by 17beta
      estradiol supplementary [with BACE to 103.5% (P < 0.01) and NEP to 88.4% (P <
      0.01)]. CONCLUSION: Estrogen depletion can increase Abeta generation through the
      effects of increased beta-secretase activity and decreased alpha-secretase
      activity. Ovariectomy also increases BACE1 expression and decreases NEP
      expression. The 17beta-estradiol supplementary can decrease Abeta generation and
      this may to some extent explain why estrogen replacement therapy can decrease the
      risk of Alzheimer's disease in postmenopausal women.

PMID- 20137688
TI  - [The diagnosis and treatment research of pancreatic cancer should be further
      strengthened].

PMID- 20137689
TI  - [Value of combined therapy in pancreatic cancer with a poor prognosis: analysis
      of 233 clinical cases].
AB  - OBJECTIVE: To analyze the value of combined therapy in pancreatic cancer with a
      poor prognosis. METHODS: The prognostic factors of pancreatic cancer with
      different clinicopathological characteristics and treatment modalities were
      analyzed retrospectively and the cumulative curve was plotted using the Kaplan
      Meier method. RESULTS: (1) From January 2001 to December 2005, 233 patients with
      pathological and cytological diagnosis of pancreatic cancer were analyzed. The
      median survival of all patients was 8.67 months, the 1-year survival rate 29.6%
      and the 5-year survival rate 4.5%. (2) Weightloss cases had a median survival of
      7.7 months versus 10.0 months for cases without weightloss (P = 0.003). Back pain
      cases had a median survival of 6.5 months versus 9.0 months for cases without
      back pain (P = 0.015). Cases with normal CA19-9 levels (< or = 37 U/ml) had a
      median survival of 11.0 months versus 8.0 months for cases with CA19-9 > 37 U/ml
      levels (P = 0.000). Stages III and IV disease cases had a median survival of 8.7
      and 6.3 months versus 16.0 months for cases of Stages I + II (P = 0.000). In the
      present study, patients suffering from weightloss or back pain or whose CA19-9
      was above 37 U/ml or whose TNM stage was III/IV were defined as cases with a poor
      prognosis. (3) Patients were grouped as pancreatectomy group, cancer-directed
      treatment group (including intraoperative iodine-125 seed interstitial
      brachytherapy, 5-FU interstitial chemotherapy, radiotherapy, chemotherapy and
      transcatheter arterial infusion chemotherapy) and no cancer-directed treatment
      group (including cases receiving biopsies or bypass). Median survival of three
      groups were 14.0, 8.3 and 6.6 months respectively. And the 1-year survival rates
      were 53.5%, 22.5% and 11.8% respectively while the 5-year survival rate 5.8%, 0
      and 0 respectively. (4) Median survival of poor prognostic cases (who suffered
      from weightloss or back pain or whose CA19-9 was above 37 U/ml or whose TNM stage
      was III/IV) treated with pancreatectomy were 12.0, 11.0, 12.0 and 7.0 months
      respectively. Median survival of poor prognostic cases treated with cancer
      directed therapy were 7.7, 7.5, 8.6 and 8.0 months respectively. Median survival
      of poor prognostic cases treated with no cancer-directed therapy were 4.0, 3.0,
      4.0 and 4.6 months respectively. CONCLUSION: Optimized combined therapy is
      recommended for pancreatic cancer patients with poor prognostic factors.

PMID- 20137690
TI  - [Expression of vascular endothelial growth factor C in pancreatic cancer and its
      effect upon lymph node metastasis].
AB  - OBJECTIVE: To investigate the expression of vascular endothelial growth factor C
      (VEGF-C) and the effect of antisense oligonucleotide (ASODN) upon lymph node
      metastasis of pancreatic cancer cell. METHODS: We selected 15 cases of human
      pancreatic cancer and detected the expression of VEGF-C in primary tumor and
      lymph node metastasis tissues with immunohistochemistry. Meanwhile, the
      spontaneous lymphatic metastasis model in nude mice was established with
      orthotopic implantation for the human pancreatic cancer cell line PANC-1,
      isolation and culture of primary tumor and spontaneous lymphatic metastasis. The
      effect of VEGF-C special ASODN upon the apoptosis of pancreatic cancer cell
      derived from primary tumor and spontaneous lymphatic metastasis were detected by
      reverse transcription polymerase chain reaction (RT-PCR), enzyme linked
      immunosorbent assay (ELISA), flow cytometer and terminal deoxynucleotidyl
      transferase mediated-dUTP nick end labeling (TUNEL). RESULTS: In tissues of human
      pancreatic cancer, the values of VEGF-C on lymph nodes metastasis were more
      higher than primary tumor (P < 0.05). About the expression of VEGF-C on
      pancreatic cancer cell derived from spontaneous lymphatic metastasis and primary
      tumor in nude mice model, the mRNA levels of VEGF-C were 0.87 +/- 0.11 and 0.61
      +/- 0.15 respectively, the VEGF-C levels in culture supernatants were (1682 +/-
      157) pg/ml and (1404 +/- 128) pg/ml. The expression of VEGF-C on pancreatic
      cancer cells derived from lymphatic metastasis were also more higher than primary
      tumor (P < 0.05). In vitro and vivo, transfection of VEGF-C ASODN decreased the
      expression of VEGF-C in pancreatic cancer cell. In control group, scramble-sense
      oligonucleotide (SODN) group and ASODN group, the apoptosis rates of pancreatic
      cancer cells derived from lymph node metastasis were (2.8 +/- 1.0)%, (5.0 +/-
      2.1)%, (13.2 +/- 2.2)% respectively in vitro, and were (1.8 +/- 0.5)%, (2.0 +/-
      0.7)%, (4.4 +/- 1.0)% respectively in vivo, the apoptosis was increased
      significantly after transfection of VEGF-C ASODN (all P < 0.01). But pancreatic
      cancer cells derived from primary tumor were not effected (all P > 0.05).
      CONCLUSION: In human pancreatic cancer and nude mice model, the expression of
      VEGF-C on lymphatic metastasis was higher than primary tumor. The apoptosis of
      pancreatic cancer cells derived from spontaneous lymphatic metastasis were
      promoted by transfection of VEGF-C ASODN specially.

PMID- 20137691
TI  - [Effect of human telomerase reverse transcriptase gene antisense oligonucleotide
      on sensitivity of gemcitabine in pancreatic cancer cell].
AB  - OBJECTIVE: To evaluate whether antisense oligonucleotides (ASODN) targeting hTERT
      mRNA could sensitize human pancreatic cancer cell to gemcitabine in vitro.
      METHODS: hTERT mRNA expression was measured by real-time quantitative reverse
      transcription polymerase chain reaction (RT-PCR) assay. Telomerase activity was
      examined by TRAP, polyacrylamide gel electrophoresis and silver staining. The
      proliferation capacity and the apoptosis of cancer cells were evaluated by MTT
      assay and double staining with both Annexin V-FITC and PI. RESULTS: Transient
      transfection in human pancreatic cancer cell with hTERT ASODN diminished the
      abundance of hTERT mRNA in a concentration-dependent fashion. And 0.2 micromol/L
      ASODN decreased the telomerase activity by 0.47-fold in cancer cell. The IC(50)
      value of gemcitabine in ASODN-transfected cell was (0.8 +/- 0.2) micromol/L while
      that in oligofectamine-transfected control cell (7.3 +/- 0.9) micromol/L with a
      statistically significant difference. hTERT ASODN significantlly increased the
      gemcitabine-induced apoptosis rate in pancreatic cancer cell. The gemcitabine
      induced apoptosis rate in ASODN-transfected cell was 60.28% while that in
      oligofectamine-transfected control cell 17.34%. CONCLUSION: hTERT antisense
      oligodeoxynucleotide can increase the sensitivity of pancreatic cancer cell to
      gemcitabine. The mechanism may be due to the down-regulated expression of hTERT
      mRNA and telomerase activity.

PMID- 20137692
TI  - [Novel NKX2-5 mutations identified in patients with congenital ventricular septal
      defects].
AB  - OBJECTIVE: To identify the novel genetic defects in patients with congenital
      ventricular septal defect (VSD). METHODS: The clinical data and blood samples
      from 160 unrelated subjects with congenital VSD were collected and evaluated in
      comparison with 200 healthy individuals. The coding exons and flanking introns of
      NKX2-5 gene were amplified by polymerase chain reaction and sequenced using the
      di-deoxynucleotide chain termination approach. The acquired sequences were
      aligned with those publicized in GenBank by the aid of program BLAST to identify
      the sequence variations. The software Clustal W was applied to analyzing the
      conservation of altered amino acids. RESULTS: Two novel heterozygous missense
      NKX2-5 mutations were identified in 3 of 160 VSD patients. The same triplet
      substitution of TTC for TCC at codon 179, predicting the conversion of serine
      into phenylalanine at amino acid residue 179 (Ser179Phe), was detected in two
      cases. Another transition of CGC into AGC at codon 36, leading to the change of
      arginine into serine at amino acid residue 36 (Arg36Ser), was detected in a third
      case. These two mutations were not observed in 200 healthy controls. A cross
      species alignment of NKX2-5 encoded protein sequences displayed that the mutated
      amino acids were highly conserved evolutionarily. Additionally, two single
      nucleotide polymorphisms including a common c. 63A > G and a rare c. 606G > C
      were observed. However, the polymorphic frequency distributions in VSD cases were
      not statistically different from those in healthy controls (c. 63A > G: chi(2) =
      3.403, P = 0.0651; c. 606G > C: chi(2) = 3.278, P = 0.0702). CONCLUSION: Novel
      NKX2-5 mutations are identified in patients with ASD. They may provide new
      insight into the molecular etiology responsible for VSD.

PMID- 20137693
TI  - [Smoking status in Chinese cardiovascular physicians in 2008].
AB  - OBJECTIVE: To investigate the prevalence and hazard of smoking in Chinese
      cardiovascular physicians. METHODS: A total of 4032 cardiovascular-certified
      physicians were recruited from 386 medical centers in all 31 provinces and
      municipalities in mainland China between June 1 2008 and August 31 2008. RESULTS:
      The prevalence of smoking in Chinese cardiovascular physicians was 15.2% (95% CI
      14.1% - 16.3%), 609 (29.8%) (95% CI 27.8% - 31.8%) for men was much higher than 3
      (0.2%) (95% CI 0.1% - 0.4%) for women (P < 0.01). The prevalence of heavy male
      smoking was 6.9% (95% CI 5.9% - 8.1%) and there was no heavy female smoker.
      Significant geographic differences were observed among male smokers. Higher
      smoking rates were seen in the northwest and southwest parts of China. There were
      significant differences in prevalence of male smoking between areas. The
      prevalence of history of hypertension, diabetes mellitus and hypercholesterolemia
      in male smoking group were all significantly higher than in male non-smoking
      group (all P < 0.01). The 10-year absolute risk and relative risk of coronary
      heart disease and ischemic cardiovascular disease estimated by Framingham model
      and Chinese model were all significantly higher in smoking group than in non
      smoking group (all P < 0.01). CONCLUSION: The prevalence of smoking in Chinese
      cardiovascular physicians is relatively high and smoking cessation should be
      targeted in this population.

PMID- 20137694
TI  - [Long-term impact on quality of life in patients with gastroesophageal reflux
      disease after 52-week rabeprazole treatment].
AB  - OBJECTIVE: To investigate the longitudinal changes in quality of life (QoL) for
      gastroesophageal reflux disease (GERD) treated with 52-week rabeprazole over a
      period of 2-3 years. METHODS: A multi-center, open-label and randomized 52-week
      rabeprazole trial was conducted in 67 eosinophilic esophagitis (EE) and 31 non
      erosive reflux disease (NERD) patients. The follow-up period is 2-3 years after
      the treatment. Their QoL were evaluated using SF-36 Health Survey Questionnaire
      and GERD-HRQL scale. The results were compared with those acquired before and
      after a 52-week proton pump inhibitor (PPI) treatment. RESULTS: (1) Both EE and
      NERD patients improved significantly according to GERD-HRQL scale in scores of
      reflux symptoms as well as overall satisfaction (12.5 vs 3.5, 20.0 vs 14.0, both
      P < 0.01) versus the pre-therapy baseline. (2) Both EE and NERD patients had no
      significant difference in the scale of GERD-HRQL (2.0 vs 3.5, 5.0 vs 4.0, both P
      > 0.05) and most major domains of SF-36 questionnaire versus the post-therapy
      baseline (53 +/- 17 vs 61 +/- 17, t = -2.143, P = 0.035). (3) The NERD patients
      had a higher score of reflux symptoms than the EE patients according to the GERD
      HRQL Scale (14.0 vs 3.5, Z = 2.377, P = 0.017), however there were no significant
      differences between NERD and EE in 8 major domains of SF-36 questionnaire (P >
      0.05). CONCLUSION: Long-term and low-dose PPI treatment achieves improvement both
      in reflux symptoms and QoL in GERD patients and such effects last a long time. At
      follow-ups, the reflux symptoms of NERD patients are more severe than EE
      patients. However, the overall QoL has shown little differences between these two
      subtypes.

PMID- 20137695
TI  - [Outcome and significance of pulmonary pathological changes induced by a single
      intramuscular injection of chemokine-like factor 1 in mice].
AB  - OBJECTIVE: To investigate the significance of pathological changes in murine lung
      by a single intramuscular injection of chemokine-like factor 1 (CKLF1). METHODS:
      A total of 120 gender-matched BALB/c mice were randomly and evenly divided into
      treatment group and control group (60 in each). One hundred nanomilligram of
      pcDNA3.1-CKLF1-Myc-His, CKLF1-expressing plasmid, in 100 microl of pyrogen-free
      saline was injected into the anterior tibial muscle of mice followed by the
      delivery of electric pulses. Mice in the control group received 100 microg of
      pcDNA3.1-Myc-His in 100 microl of pyrogen-free saline. At the end of week 1, 4
      and 8 respectively after injection of CKLF1, 20 mice were sacrificed in every
      group and the cellular profiles in bronchoalveolar lavage fluid (BALF) and the
      pulmonary pathological changes were observed. RESULTS: At the end of week 1 and 4
      respectively after CKLF1 injection, the neutrophils [(35.0 +/- 5.2)% and (22.9 +/
      2.2)% respectively] and lymphocytes [(34.5 +/- 2.8)% and (22.0 +/- 2.0)%
      respectively] in BALF of the treatment group were higher than those of the
      control group [neutrophils: (6.7 +/- 2.2)% and (7.0 +/- 2.4)% respectively,
      lymphocytes: (5.9 +/- 1.6)% and (6.1 +/- 2.7)% respectively, all P < 0.01].
      Pathological studies demonstrated shedding of bronchiolar epithelium, congestion
      and edema in interstitial tissue and inflammatory cell infiltration in mice at 1
      week after CKLF1 injection. Week 4 after CKLF1 administration, the alveolar wall
      was shown significantly thickened with proliferation of neutrophils, macrophages
      and fibroblasts as well as remarked collagen deposition in the interstitium. At
      the end of week 8 after CKLF1 administration, the remarkable morphological
      changes of the lung gradually subsided and the structure of the lung returned to
      normal. CONCLUSIONS: CKLF1 causes injury of inflammation and remodeling in airway
      in mice. The pulmonary pathological changes induced by a single intramuscular
      injection of CKLF are reversible.

PMID- 20137696
TI  - [Sympathetic nerve in rat with pressure overload left ventricular hypertrophy].
AB  - OBJECTIVE: To explore the remodeling mechanism of myocardium and sympathetic
      nerve in pressure overload left ventricular hypertrophy and elucidate the
      protective effect of statins. METHODS: Pressure-overload left ventricular
      hypertrophy (LVH) of rats was induced by partial coarctation of abdominal aorta;
      a sham-operated group served as the control (SHAM, n = 22). At 8 weeks post
      operation, the animals were divided into two groups and a 12-week treatment
      period was investigated. At the end of treatment period, echocardiographic
      evaluations and hemodynamic measurements were performed. Sympathetic innervation
      was investigated by analyzing nerve growth factor (NGF), growth associated
      protein-43 (GAP43) and tyrosine hydroxylase (TH). RESULTS: In LVH rats, a
      significant increase of left ventricular weight, left ventricular weight/body
      weight, echocardiographic left ventricular end-diastolic diameter,
      interventricular septum thickness, posterior left ventricular wall thickness,
      left ventricular systolic pressure and dP/dt was observed. The expressions of NGF
      and GAP43 protein were significantly down-regulated (0.82 +/- 0.06 vs 1.53 +/-
      0.10, 0.68 +/- 0.06 vs 0.81 +/- 0.10) and TH level was up-regulated (0.44 +/-
      0.10 vs 0.62 +/- 0.06) by RSV treatment. CONCLUSION: A HMG CoA inhibitor reverses
      the development of left ventricular hypertrophy and inhibits sympathetic
      innervation in abdominal aortic-clamped animals.

PMID- 20137697
TI  - [Effects of nuclear factor-kappaB siRNA upon dextran sulphate sodium-induced
      colitis murine model].
AB  - OBJECTIVE: To investigate the effects of nuclear factor-kappaB (NF-kappaB) siRNA
      upon dextran sulphate sodium (DSS)-induced colitis. METHODS: Thirty-six BALB/C
      mice were randomly divided into 4 groups: normal control group, NF-kappaB siRNA,
      scrambled siRNA and DSS group. Colitis was induced by treatment with 5% DSS in
      drinking water and evaluated by disease activity index (DAI) and histological
      score. The tumor necrosis factor (TNF-alpha) level of colonic mucosa was measured
      by enzyme linked immunosorbent assay (ELISA). NF-kappaB p65 expression was
      determined by immunohistochemical staining. RESULTS: Compared with the scrambled
      siRNA (DAI 3.42 +/- 0.67, histological score 4.65 +/- 1.53) and DSS group (3.73
      +/- 0.55, 4.47 +/- 1.52), a significant decrease was observed in DAI (2.31 +/-
      0.26) and histological score (2.19 +/- 0.77) in mice with NF-kappaB p65 siRNA
      (both P < 0.05). The expression of NF-kappaB p65 and TNF-alpha [(266 +/- 35)
      pg/ml] in mice with DSS-induced colitis was significantly reduced after treatment
      with NF-kappaB p65 siRNA (P < 0.05) in comparisons with the scrambled siRNA [(412
      +/- 51) pg/ml] and DSS group pg/ml [(449 +/- 44) pg/ml]. CONCLUSION: NF-kappaB
      p65siRNA shows protective effects upon the mice with DSS-induced colitis.
      Blockade of NF-kappaB pathway by NF-kappaB p65 siRNA may serve as a novel gene
      therapy for ulcerative colitis.

PMID- 20137698
TI  - [Effects of respiratory syncytial virus upon expressions of mRNA and protein of
      intercellular adhesion molecule-1 in human embryonic lung fibroblast cells].
AB  - OBJECTIVE: To explore the effects of respiratory syncytial virus (RSV) upon the
      expressions of mRNA and protein of intercellular adhesion molecule-1 (ICAM-1) in
      human embryonic lung fibroblast cells. METHODS: The expressions of mRNA and
      protein of ICAM-1 were determined in human embryonic lung fibroblast cells after
      being infected by the LONG strain type A RSV and in normal fibroblast cells with
      real-time PCR and flow cytometry. RESULTS: The mRNA of ICAM-1 expression in human
      embryonic lung fibroblast cells was 2.51 times at 24 h post-infection as that in
      normal fibroblast cells (P < 0.05). The protein of ICAM-1 expression of RSV
      control group (1.25 +/- 0.09, 1.87 +/- 0.18, 4.78 +/- 0.52, 13.34 +/- 0.64, 1.58
      +/- 0.37) were significantly higher than those of normal cell group (0.21 +/-
      0.06, 0.30 +/- 0.06, 0.29 +/- 0.07, 0.35 +/- 0.17, 0.35 +/- 0.14) at 12, 24, 48,
      72 and 96 h post-infection (all P < 0.01). The protein of ICAM-1 expression of
      RSV control group achieved a peak value between 48 h and 72 h, and then it
      decreased significantly at 96 h. CONCLUSION: Lung fibroblast cell and ICAM-1 may
      play some roles in pathogenic mechanism of RSV viral pneumonia.

PMID- 20137699
TI  - [Role of inhibition of transcription factor forkhead box M1 expression by RNA
      interference in the proliferation and invasiveness of non-small cell lung cancer
      cells].
AB  - OBJECTIVE: To investigate the change of proliferation and invasiveness of non
      small cell lung cancer (NSCLC) cell lines SPC-A-1, A549 and LTEP-a-2 with
      forkhead box M1 (FoxM1) expression deficiency. METHODS: A siRNA targeting FoxM1
      was designed to deplete the FoxM1 expression of these cell lines and an unrelated
      siRNA used as control. Real-time RT-PCR and Western blotting were used to examine
      the FoxM1 expression in mRNA and protein level respectively. Colony assay, wound
      healing assay and transwell chamber assay were employed to evaluate the colony
      formation ability and invasiveness of FoxM1 deficient cells. RESULTS: The
      designed siRNA could efficiently deplete FoxM1 expression by 83.9%, 83.6% and
      88.6% in SPC-A-1, A549 and LTEP-a-2 cell lines respectively. Real-time RT-PCR and
      Western blot test showed that the FoxM1 protein was also depleted. The colony
      formation numbers (136.0 +/- 15.5, 87.0 +/- 2.6 and 121.7 +/- 9.4 respectively)
      and invasion cell numbers (19.2 +/- 2.5, 4.2 +/- 0.8 and 6.2 +/- 1.8
      respectively) of FoxM1 deficient SPC-A-1, A549 and LTEP-a-2 cell lines were
      significantly fewer than those of the unrelated-siRNA transfected group (colony
      formation numbers were 222.3 +/- 20.5, 164.7 +/- 14.1 and 260.7 +/- 13.5
      respectively, and invasive cell numbers were 81.4 +/- 6.2, 39.2 +/- 4.6 and 35.6
      +/- 3.0 respectively, all P < 0.01). The cell migration rate of siFoxM1 deficient
      SPC-A-1 (52.6% +/- 7.8%) was significantly lower than that of the unrelated-siRNA
      transfected group (85.3% +/- 18.6%, P < 0.01). CONCLUSIONS: The proliferation and
      invasiveness of several NSCLC cell lines were significantly inhibited after the
      FoxM1 gene expression was depleted. It suggests that inhibiting the FoxM1
      expression might be a promising way for lung cancer therapy.

PMID- 20137700
TI  - [Preliminary effects of alcohol and Curcuma longa upon CYP2E1 and hematotoxicity
      in benzene-induced mice].
AB  - OBJECTIVE: To observe the effects of CYP2E1 enzymatic alteration upon
      hematotoxicity by benzene poisoning in mice and the interference of alcohol and
      Curcuma longa. METHODS: Eighty male Kunming mice (KM) were randomly divided into
      four groups: group A (20 mice injected subcutaneously with sodium chloride 2
      ml/kg once every 2 days for 3 weeks as normal control group); group B (20 mice
      injected subcutaneously with 2 ml/kg benzene once every 2 days for 3 weeks as
      model group); group C (20 mice drinking freely 10% alcohol per day on the basis
      of benzene poisoning model as alcohol-treated group) and group D (20 mice given
      Curcuma longa 3 g/kg once a day on the basis of benzene poisoning model as
      Curcuma-treated group). Then the blood samples were collected so as to count the
      parameters of WBC, Hb, PLT. In addition, the liver cytochrome P450 activity and
      MN formation rate were measured. RESULTS: (1) Compared with group A, WBC, Hb and
      PLT of group B significantly decreased [(2.6 +/- 1.0) x 10(9)/L, (93 +/- 11) g/L,
      (593 +/- 81) x 10(9)/L]. (2) Compared with group B, the parameters of group C
      decreased (P < 0.05) while the liver cytochrome P450 activity of group C
      increased. It indicated that alcohol improved the activity of CYP2E1 and the MN
      formation rate of group C also increased [(8.8 +/- 1.8) per thousand vs(6.5 +/-
      1.0) per thousand, P < 0.01]. (3) Compared with group B, the parameters of group
      D improved (P < 0.01). The activity of CYP2E1 of group D decreased and the
      difference was significant (P < 0.01). In the meantime, MN formation rate
      decreased (P < 0.01). CONCLUSIONS: (1) When the liver cytochrome P450 activity
      were altered, the hematotoxicity of benzene poisoning in mice underwent changes.
      (2) Alcohol increases the hematotoxicity induced by benzene poisoning in mice.
      (3) Curcuma longa has preventive effect against the hematotoxity of benzene.

PMID- 20137701
TI  - [Osteoporosis epidemiology update].

PMID- 20137702
TI  - [Nonclassic actions of vitamin D and its clinical significance].

PMID- 20137703
TI  - [Osteoprotegerin gene polymorphism and therapeutic response to alendronate in
      postmenopausal women with osteoporosis].
AB  - OBJECTIVE: To investigate whether the polymorphism of osteoprotegerin (OPG) gene
      is associated with the change of BMD (bone mineral density) after alendronate
      therapy in postmenopausal women with osteoporosis and determine the correlation
      between genotypes and therapeutic effect. METHODS: Eighty postmenopausal
      osteoporotic patients were recruited with an average age of (64.2 +/- 7.7) years
      old. Every patient took oral alendronate (Fosamax) 70 mg weekly and Caltrate 600
      mg daily for 12 months. At pre- and post-treatment, BMD was measured at lumbar
      spine 2 - 4 and hip sites. PCR-RFLP was performed for three polymorphisms at the
      promoter site of OPG gene (A163G, T245G and T950C). RESULTS: One-year therapy was
      accomplished in 67 patients. Patients with G allele (genotype AG and GG) of site
      A163G, the baseline BMD of vertebral L2-4, inter-troche and total hip were lower
      than genotype AA [(0.732 +/- 0.113) g/cm(2) vs (0.819 +/- 0.157) g/cm(2), (0.775
      +/- 0.101) g/cm(2) vs (0.843 +/- 0.124) g/cm(2) and (0.667 +/- 0.105) g/cm(2) vs
      (0.725 +/- 0.091) g/cm(2)]. Patients with G allele (genotype TG and GG) of site
      T245G, baseline BMD of vertebral L2-4, inter-troche and total hip were lower than
      genotype TT [(0.723 +/- 0.111) g/cm(2) vs (0.819 +/- 0.155) g/cm(2), (0.776 +/-
      0.102) g/cm(2) vs (0.840 +/- 0.124) g/cm(2) and (0.670 +/- 0.109) g/cm(2) vs
      (0.721 +/- 0.091) g/cm(2)]. After one-year therapy, at site A163G, the percentage
      of BMD change at inter-troche was higher in genotype AA than in genotypes AG and
      GG [2.50 (3.47)% vs 0.88% (3.47%)%, P = 0.014]. While at site T245G, the
      percentage of BMD change at inter-troche and total hip were higher in genotype TT
      than in genotype TG and GG 2.50% (3.47%) vs 0.61% (3.31%), P = 0.011; 2.72%
      (2.68%) vs 0.89 (3.01%), P = 0.046]. CONCLUSION: The G allele of sites A163G and
      T245G may be the risk allele of postmenopausal osteoporosis. Furthermore,
      patients with genotypes AA (A163G) and (T245G) show a better therapeutic effect
      to alendronate.

PMID- 20137704
TI  - [Bone mass change and its possible mechanisms in murine knockout apolipoprotein
      E(ApoE-/-)].
AB  - OBJECTIVE: To study bone mass changes and its mechanisms in murine knockout
      apolipoprotein E (ApoE-/-). METHODS: Both 28-week-old male ApoE-/- mice (n = 6)
      and wild-type (WT) mice (n = 10) were euthanized. The trabecular and cortical
      bone microarchitecture were assessed by micro-CT (microCT) in right distal femur.
      The total body BMD (bone mineral density) of left femur was determined by dual
      energy X-ray absorptiometry (DXA). The serum concentrations of osteoprotegerin
      (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) were
      analyzed using enzyme-linked immunosorbent assay (ELISA). The left tibias were
      dissected and fixed in 4% paraformaldehyde after decalcified in 0.15M EDTA buffer
      for 30 days. And the expressions of OPG and RANKL were detected by
      immunohistochemical staining. RESULTS: Compared with WT mice, the ApoE-/- mice
      showed an increased volumetric BMD (294 +/- 38) mg/mm(3), tissue BMD (627 +/- 23)
      mg/mm(3), BMC (bone mineral content) (0.57 +/- 0.08) mg, bone volume fraction
      (20.38 +/- 4.74)%, trabecular number (6.67 +/- 0.78) mm(-1), trabecular thickness
      (0.03 +/- 0.01) mm with an decreased bone surface fraction (69 +/- 18) mm(-1),
      trabecular separation (0.12 +/- 0.01) and structure mode index (1.73 +/- 0.24).
      The total body BMD was higher in ApoE-/- mice than WT mice [(0.063 +/- 0.004)
      g/cm(2) vs (0.056 +/- 0.004) g/cm(2)]. The serum level of OPG was significantly
      higher in ApoE-/- mice than WT mice [(4.98 +/- 0.97) ng/ml vs (3.54 +/- 0.65)
      ng/ml]. The results of immunohistochemical staining showed that the OPG
      expression was at a higher level in bone cell of ApoE-/- mice and RANKL showed no
      obvious change in either sera or bone cells. CONCLUSION: A decreased bone
      resorption causes an increased bone mass in ApoE-/- mice and leads to an
      imbalanced ratio of OPG/ RANKL.

PMID- 20137705
TI  - [Long-term and high-dose bisphosphonate administration causes no bone over
      mineralization].
AB  - OBJECTIVE: To evaluate the effects of long-term bisphosphonate administration
      (incadronate) upon the mean degree of secondary bone mineralization. METHODS:
      Thirty adult beagles were divided randomly into three groups of CNT, YML and YMH
      based upon their body weights (5 males and 5 females in each group). Animals in
      CNT were orally given lactose 12 mg x kg(-1) x d(-1) while those in YML and YMH
      were orally given incadronate disodium at doses of 0.3 mg x kg(-1) x d(-1) and
      0.6 mg x kg(-1) x d(-1) respectively. The dosing procedure lasted for three
      years. Prior to sacrifices, all animals were double-labeled intravenously with
      oxytetracycline hydrochloride (20 mg x kg(-1)). After necropsy, the left 9th ribs
      were excised for evaluation. RESULTS: Histomorphometry showed that activation
      frequency in YML and YMH [(4.93 +/- 0.92)/mm(2) and (2.50 +/- 0.78)/mm(2)] were
      significantly lower than that in CNT (7.83 +/- 0.96)/mm(2) per year. The mean
      degree of mineralization in bone in YML and YMH (1.40 +/- 0.12, 1.48 +/- 0.09)
      were significantly higher than CNT (1.07 +/- 0.06). The increments were 31% and
      38% respectively. CONCLUSION: Long-term and high-dose bisphosphonate
      administration significantly suppresses bone turnover so as to increase the
      degree of bone mineralization. But there is no resulting bone over
      mineralization. (incadronate) administration on the mean degree of secondary
      mineralization in bone.

PMID- 20137706
TI  - [Role of the cross-talk between estrogen receptors and peroxisome proliferator
      activated receptor gamma in daidzein's prevention and treatment of osteoporosis
      in ovariectomized rats].
AB  - OBJECTIVE: To investigate the role of the cross-talk between estrogen receptors
      and peroxisome proliferator-activated receptor gamma in daidzein's prevention and
      treatment of osteoporosis in the ovariectomized rats. METHODS: Sixty four-month
      old Sprague-Dawley (SD) female rats were divided into six groups. Four weeks
      after the establishment of osteoporosis model, the ovariectomized rats were
      administered different drugs by gavage respectively for three months. After
      sacrificing, the expressions of mRNA of ERalpha, ERbeta and PPARgamma in L(6) and
      right femur were measured by realtime-RT-PCR, while proteins were detected by
      immunohistochemistry. RESULTS: The expressions of ERalpha mRNA and protein were
      significantly lower than that of ERbeta in three dosing groups. Excepting that of
      rat femur of rats in H-Dai group, the expressions of ERbeta mRNA of lumbar spine
      and femur in M-Dai group (0.0177 +/- 0.0010, 0.0245 +/- 0.0013) and L-Dai groups
      (0.0276 +/- 0.0027, 0.0278 +/- 0.0044) and lumbar spine in H-Dai group (0.0163 +/
      0.0037) were significantly higher than that in OVX group (0.0016 +/- 0.0005,
      0.0041 +/- 0.0014). There was no significant difference with E(2) group. At the
      same time, the expression of ERbeta protein showed into the similar trend as that
      of mRNA. And there was an rising expressions of ERbeta while daidzein dose
      decreased. On the contrary, the expressions of PPARgamma mRNA and protein
      decreased. CONCLUSIONS: There is an inverse cross-talk relationship between
      ERbeta and PPARgamma, it may play a role in daidzein's prevention and treatment
      of osteoporosis in ovariectomized rats.

PMID- 20137707
TI  - [Urinary function after pelvic autonomic nerve preservation of laparoscopic
      radical resection for rectal cancer].
AB  - OBJECTIVE: To evaluate the protection of urinary function after laparoscopic
      radical resection with pelvic autonomic nerve preservation (PANP) for rectal
      cancer. METHODS: Prospectively 139 patients with middle or low rectal cancer
      receiving surgery during November 2005 to October 2007 were divided into two
      groups (L-PANP, n = 63; O-PANP, n = 76). The radicalism and safety of L-PANP
      surgery were analyzed and the effects upon urinary function between the two
      groups assessed by follow-ups and urodynamic study. RESULTS: Patients receiving
      subtypes I and II of L-PANP surgery had less decrease in contraction of bladder
      than those receiving the same subtype of O-PANP surgery at 10 days post-operation
      (Z = -2.358, P = 0.018; Z = -2.268, P = 0.033). And no difference was observed in
      patients receiving subtype III PANP surgery (Z = -1.302, P = 0.237). However, no
      matter which subtype of PANP surgery, patients of L-PANP group had a better
      contraction of bladder than those of O-PANP group at 1 month post-operation (P <
      0.05). The 1-year survival rate was 98.0% (50/51) in L-PANP group and 96.6%
      (57/59) in O-PANP group. And no statistical difference was found between them (P
      = 0.898). Meanwhile, the 1-year relapse rate of pelvic cavity was 3.9% (2/52) in
      L-PANP group and 5.1% (3/59) in O-PANP group. And no statistical difference was
      found between them (P = 0.867). CONCLUSION: As compared with O-PANP surgery, L
      PANP surgery shows a superiority in protection of urinary function.

PMID- 20137708
TI  - [Effects of obstructive sleep apnea-hypopnea syndrome upon cardiac structure and
      function].
AB  - OBJECTIVE: To investigate the effects of obstructive sleep apnea-hypopnea
      syndrome (OSAHS) upon cardiac structure and function of patients. METHODS:
      According to apnea hypopnea index, 75 OSAHS patients were divided into three
      groups: mild (n = 25), moderate (n = 25) and serious (n = 25); according to the
      course of disease, < 5 years (n = 22), 5-10 years (n = 26) and > 10 years (n =
      27). The control group included 25 healthy adults. All subjects received
      polysomnogram and echocardiography. The following parameters were recorded:
      aortic dimension, pulmonary artery inner diameter, chambers heart size,
      interventricular septal thickness, anterior wall thickness and movement extent of
      end-diastole right ventricle, left ventricular ejection fraction (LVEF),
      shortening fraction (FS) and E/A ratio, etc. RESULTS: Pulmonary artery inner
      diameter of mild, moderate, serious and control groups were (21.4 +/- 2.5), (24.7
      +/- 2.0), (26.7 +/- 2.1), (21.2 +/- 2.7) mm, right ventricle internal diameter
      (19.0 +/- 1.8), (22.0 +/- 2.1), (23.9 +/- 2.1), (18.9 +/- 1.8) mm, and anterior
      wall thickness of right ventricle (4.7 +/- 1.2), (6.5 +/- 1.3), (7.5 +/- 1.4),
      (4.1 +/- 1.0) mm. The moderate and serious groups were all higher than control
      and mild groups obviously (P < 0.01). The serious group was higher than the
      moderate group (P < 0.01). LVEF of four groups: (63.1 +/- 8.1)%, (60.0 +/-
      10.2)%, (54.5 +/- 9.1)%, (63.6 +/- 7.7)%, FS: (38.1 +/- 4.3)%, (37.0 +/- 6.4)%,
      (33.6 +/- 5.4)%, (39.5 +/- 4.9)%, and E/A: (1.13 +/- 0.13), (0.96 +/- 0.16),
      (0.85 +/- 0.12), (1.28 +/- 0.15). LVEF and FS of the serious group were lower
      than those of the control, mild and moderate groups (P < 0.05). E/A ratio of the
      mild, moderate and serious groups were lower than the control group (P < 0.01).
      The interclass comparison of mild, moderate and serious groups had significant
      differences (P < 0.01). Right ventricle internal diameter, pulmonary artery inner
      diameter, anterior wall thickness of right ventricle of > 10 years group were
      higher than 5-10 years group obviously (P < 0.05, P < 0.01). The 5-10 years group
      was higher than the < 5 years and control groups obviously (P < 0.05, P < 0.01).
      LVEF, FS, and E/A ratio of > 10 years group were lower than 5-10 years, < 5 years
      and control groups obviously (P < 0.05, P < 0.01). CONCLUSION: OSAHS causes
      structural and functional cardiac changes worsening with disease aggravation and
      course extension.

PMID- 20137709
TI  - [Resistance study of community respiratory pathogens isolated in China from 2005
      to 2007].
AB  - OBJECTIVE: To investigate the antimicrobial resistance of community respiratory
      pathogens isolated in China. METHODS: The strains of Streptococcus pneumoniae,
      Haemophilus influenzae, Moraxella catarrhalis, S. pyogenes were isolated from
      patients with community-acquired respiratory tract infections at 14 Chinese
      hospitals from 2005 to 2007. Etest and disk diffusion methods were used to survey
      the susceptibility of 14 antibiotics against these strains. These antibiotics
      included penicillin G, ampicillin, amoxicillin/clavulanic acid, cefaclor,
      cefprozil, ceftriaxone, cefepime, levofloxacin, gatifloxacin, ciprofloxacin,
      tetracycline, clindamycin, erythromycin and trimethoprim/sulfamethoxazole (SXT).
      RESULTS: A total of 1870 strains were collected including S. pneumoniae (n =
      997), S. pyogenes (n = 176), H. influenzae (n = 499) and M. catarrhalis (n =
      198). The 2005 - 2007 prevalence of penicillin-susceptible S. pneumoniae (PSSP)
      were 92.6%, 73.9%, 74.1% and penicillin-intermediate S. pneumoniae (PISP) 4.5%,
      9.5%, 14.3% and penicillin-resistant S. pneumoniae (PRSP) 2.9%, 16.6%, 11.6%
      respectively. 36.9% of S. pneumoniae strains isolated from <or= 6 years old
      children were penicillin-non-susceptive isolates (PNSSP) and < 22.0% of PNSSP
      isolated from other age groups. The susceptible rates of beta-lactamase
      antibiotics to PRSP and PISP isolates were less than 25.0% and 49.2%
      respectively. From 48.5% to 98.6% PSSP isolates were susceptible to beta
      lactamase antibiotics. The susceptible rates of PNSSP and PSSP to erythromycin,
      tetracycline and SXT were below 7.1% and 32.1% respectively. About 95% S.
      pneumoniae were susceptible to ciprofloxacin, levofloxacin and gatifloxacin. All
      of S. pyogenes isolates were susceptible to beta-lactamase antibiotics, and
      16.7%, 27.1% and 15.6% Of S. pyogenes isolates were susceptible to erythromycin.
      8.5%, 19.9%, 15.3% of H. influenzae and 57.4%, 78.8%, 95.5% of M. catarrhalis
      produced beta-lactamase during the 3-year period. The susceptible rates of
      cefepime, ceftriaxone, gatifloxacin, levofloxacin and ciprofloxacin to H.
      influenzae and M. catarrhalis were >or= 92.9%. CONCLUSIONS: Antimicrobial
      resistance in S. pneumoniae is rising. The prevalence of PNSSP isolated from
      children < or = 6 years old is higher than other age groups. Amoxicillin
      clavulanic acid, ceftriaxone, cefepime, gatifloxacin and levofloxacin remain
      highly active against common community respiratory pathogens.

PMID- 20137710
TI  - [Effect of atorvastatin on postoperative atrial fibrillation in patients
      undergoing coronary artery bypass grafting].
AB  - OBJECTIVE: To evaluate the effect of atorvastatin on postoperative atrial
      fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG).
      METHODS: A cohort of 140 consecutive patients without a history of documented AF
      or previous statin use, who were scheduled to undergo selective CABG, were
      enrolled. Included patients were randomly assigned to atorvastatin group (n = 71)
      who were administered atorvastatin 20 mg/d or to control group (n = 69). After
      CABG, subjects were monitored continuously by electrocardiographic monitors at
      least 7 days. During the initial postoperative 7 d, the incidence and duration of
      AF were recorded. And the levels of high-sensitivity C-reactive protein (hs-CRP)
      were measured before and 24 hours, 72 hours, 7 days after operation,
      respectively. The statistical software package SPSS (version 13.0) were used to
      analyze the data. The differences between groups were evaluated by chi(2)-test
      for discrete variables and student t-test for continuous variables. Multivariate
      logistic regression analysis was performed to determine the independent
      predictors of early postoperative AF. RESULTS: During initial postoperative 7 d,
      AF occurred at least once in 10 cases in atorvastatin group, with a prevalence of
      roughly 14%, and in 23 cases in control group, with a prevalence of approximately
      34% (P = 0.009). The mean duration of single AF was 3.6 +/- 0.4 hours in
      atorvastatin group and 5.7 +/- 0.5 hours in control group (P < 0.01),
      respectively. The multivariate logistic analysis showed that perioperative
      atorvastatin administration was an independently risk factor for early
      postoperative AF (OR = 0.219, 0.076-0.633, P = 0.005). There was also statistical
      difference in hs-CRP after CABG between the two groups. CONCLUSIONS:
      Perioperative atorvastatin administration may inhibit inflammatory reaction,
      reduce the incidence and duration of postoperative AF, hence may prevent and
      treat postoperative AF.

PMID- 20137711
TI  - [Establishment of irritable bowel syndrome rat model by combination of intestinal
      infection with Trichinella spiralis and acute stress].
AB  - OBJECTIVE: To establish the irritable bowel syndrome (IBS) rat model by the
      combination of acute stress and transient intestinal infection with Trichinella
      spiralis (T.S.). METHODS: The rat model of acute cold restraint stress post
      infection (PI + ACRS) was established as following: the intestinal infection with
      1500 T.S. in 1 ml saline to adult male BN rats was performed at Day 0 by gastric
      lavage. Then a 2-hour stimulus of ACRS was administered at Day 100. Age matched
      transiently infected without stress rats (PI) and normal rats served as controls
      (CON) (n = 6, for each). After anesthesia, all the rats underwent colonic
      manometry in vivo at Day 100. The colonic pressures at 3 different states
      (baseline for 20 min; 1 ml balloon distension stimulation for 5 min and 2 ml
      balloon distension stimulation for 20 min) were traced with a 5-minute interval
      between each two. The following parameters were recorded: (1) Duration (Dur.):
      total time of contractions during each state. (2) Maximum (Max.): highest
      amplitude of constructional waves (mm Hg). (3) Area: area under contraction
      waves. (4) Number (Num.): frequencies of contraction wave during each state. The
      visceromoter response to colorectal distension (CRD) was analyzed at Day 100 post
      infection. And the distension volume of AWR 3 was detected for 5 times with a 20
      min interval in each rat. RESULTS: The histological damage of intestine induced
      by T.S. infection is transient. Although such acute infectious features as
      epithelial edema, hyperemia and marked eosinophil infiltration appeared at Day 10
      PI, the histological changes almost recovered at Day 100 PI in both the PI group
      and the PI + ACRS group. Both the stimuli of transient infection and the ACRS
      post-infection induced intestinal dysmotility and visceral hypersensitivity. The
      ACRS post infection further worsened the transiently induced infection. The
      parameters of Num, Max and Area in the PI + ACRS group were all significantly
      higher than those of the PI group [Max: (41 +/- 17) mm Hg vs (22 +/- 6) mm Hg, P
      = 0.000; Area: (7693 +/- 2822) mm Hg.s vs (5092 +/- 1687) mm Hgxs, P = 0.000;
      Num: 9.5 +/- 2.6 vs 6.6 +/- 3.1, P = 0.000]; so was the distension volume of AWR3
      [(2.25 +/- 0.29) ml vs (2.52 +/- 0.32) ml, P = 0.004]. As compared with the range
      of normal values from controls, the abnormality rates of motility parameters and
      visceral threshold in PI + ACRS group also had an larger increment than those of
      the PI group (PI + ACRS: 50.0% - 87.5% and 100% respectively, PI: 25.0% - 37.5%
      and 90.0% respectively). CONCLUSION: The pathophysiological changes in the PI +
      ACRS rats are consistent with those of IBS. Aggravated by psychological factors,
      these rats reproduce the symptoms of intestinal dysmotility and visceral
      hypersensitivity. A proper animal model has been established for the
      investigation of IBS.

PMID- 20137712
TI  - [Ursodeoxycholic acid inhibits hepatocyte-like cell apoptosis by down-regulating
      the expressions of Bax and Caspase-3].
AB  - OBJECTIVE: To investigate the mechanism of ursodeoxycholic acid (UDCA) in
      hepatocyte apoptosis using differentiated hepatocytes derived from bone marrow
      mesenchymal cells. METHODS: Rat bone marrow mesenchymal cell was induced into
      mature hepatocytes in vitro and then treated with PBS (Cont), deoxycholic acid
      (DCA), DCA plus UDCA (U + D) or UDCA alone (UDCA). Cell apoptosis was detected by
      Hoechst staining and Caspase-3 activity measurement. The mRNA expressions of p53
      and Bax were measured by semi-quantitative RT-PCR and real-time RT-PCR. The Bax
      protein expression was detected by immunohistochemistry. RESULTS: In comparison
      with Cont, DCA obviously induced hepatocyte apoptosis as measured by an increased
      cell count and a higher Caspase-3 activity (P < 0.05). These increments could be
      inhibited by addition of UDCA. The expressions of p53 and Bax in hepatocytes were
      up-regulated by DCA. These up-expressions could also be inhibited by UDCA. The
      DCA-induced increased count of Bax-positive cells could be reduced by UDCA.
      CONCLUSION: UDCA inhibits DCA-induced hepatocyte apoptosis by down-regulating the
      expression of p53/Bax signal molecule.

PMID- 20137713
TI  - [Screening specific allergens of allergic asthma from DNA expression library of
      Humulus pollen].
AB  - OBJECTIVE: To screen the allergic asthma-specific allergen from complementary DNA
      (cDNA) expression library of Humulus pollen. METHODS: Screened the Humulus pollen
      lambdaTripIEx2 cDNA expression library which had been constructed using the
      method of immunological screening with patients' blood serum of Humulus pollen
      allergic asthma, extracted the positive phage DNA and the positive phage DNA, and
      identified by double restriction enzyme with EcoRI, Hind III and agarose gel
      electrophoresis. Then the DNA fragments were sequenced and the repeats and
      sequence homology were analyzed. RESULTS: After 3 rounds of screening, three
      specific allergic cDNA clone of Humulus pollen were obtained and the sequences
      were 868, 550 and 592 base pairs respectively. The results of sequencing showed
      that these three clones represented different cDNA sequences. The repeats
      analysis found no repeats and these clones had no high homology with any known
      gene. CONCLUSIONS: Three specific allergic cDNA clones of Humulus pollen obtained
      may be new genes. It provides a rational basis for constructing a recombinant
      allergen or nuclear acid vaccine.

PMID- 20137714
TI  - [The isolating culture of neural stem cells from rat's fetus brain and
      transfection by electroporation].
AB  - OBJECTIVE: To isolate and culture the neural stem cells (NSC) from rat's fetus
      brain, to study the transfection efficacy of NSC using electroporation. METHODS:
      We isolated, cultured and amplified NSC from the brain of SD fetal rats. NSC and
      differentiated cells were identified using immunofluorescent histochemical
      methods. Using green fluorescence protein (GFP) as the marker, pEGFP-N1 was
      transfected into NSC using electroporation, and the transfection rate was
      calculated by counting the NSCs with green fluorescent. RESULTS: The cells
      isolated from brain tissue of fetal rats can proliferate for long time, both
      primary and passage culture of NSC can express specific antigen of NSC-Nestin,
      and after induced differentiation, the cells can express specific antigen of
      astrocytes-Glial fibrillary acidic protein (GFAP) and specific antigen of neurons
      Neuron-specific enolase (NSE). The transfection rates of electroporation were
      17.9% - 69.1%, the average was 30.5%. CONCLUSION: Isolated NSC which had the
      features of self-proliferation and differentiation potential from brain tissue of
      SD fetal rats, confirmed that electroporation was an efficient transfection
      method for NSC, provided experimental basis for gene therapy in the future.

PMID- 20137715
TI  - [Application of eversion embolectomy for portal vein thrombosis on liver
      transplantation].
AB  - OBJECTIVE: To discuss the technical improvement of the conventional thrombectomy
      for portal vein thrombosis (PVT) on liver transplantation. METHODS: The clinical
      data of 198 cases of liver transplantation with PVT who admitted in Tianjin First
      Central Hospital were analyzed retrospectively. According to the different
      treatments for PVT, these cases were divided into group A and group B. The
      conventional eversion embolectomy were performed in group A (n = 43) and the
      improved eversion embolectomy were performed in group B (n = 155). The general
      conditions, blood loss volumes, the achievement ratio of embolectomy, PVT
      recurrence rate and survival rate between the two groups were compared. RESULTS:
      No statistical significance on operation time between two groups (P > 0.05); the
      achievement ratio of embolectomy for Yerdel I-II were 100% in two groups,
      however, the achievement ratio of embolectomy for Yerdel III in group B was
      higher than that of group A (100% vs. 45.45%; chi(2) = 12.38, P < 0.01). Blood
      loss volumes in group B was significantly lower than that of group A [(4315.4 +/-
      630.5) ml vs. (3509.2 +/- 862.7) ml, P < 0.05]. No statistical significance on
      Yerdel I and II PVT recurrence rate between two groups (P > 0.05). While
      thrombosis recurrent rate of Yerdel III PVT in group B was lower than that of
      group A(5.6% vs. 2/5; chi(2) = 4.09, P < 0.05). Perioperative mortality of Yerdel
      I-III patients were both 0 in two groups. 1-year survival rate of Yerdel I-III
      patients was similar in two groups (86.5% vs. 89.0%, P > 0.05). CONCLUSIONS:
      Improved eversion embolectomy can simplify the operation procedures, reduce blood
      loss, expand application range, increase the embolectomy success rate, decrease
      the PVT relapse rate.

PMID- 20137716
TI  - [Surgical treatment and prognosis analysis of localized retroperitoneal Castleman
      disease: a study of 20 cases].
AB  - OBJECTIVE: To investigate the clinical characteristics, surgical treatment and
      prognosis analysis of localized retroperitoneal Castleman disease (CD), and to
      improve the level of diagnosis and treatment of retroperitoneal Castleman disease
      with paraneoplastic pemphigus (PNP). METHODS: The clinical data of
      retroperitoneal CD with PNP from January 1993 to May 2009 were compared with CD
      without PNP retrospectively, including clinical features, tumor site, lab
      examination, surgical treatment, pathologic subtype and results of surgery.
      RESULTS: (1) Retroperitoneal Castleman disease more likely originated in para
      kidney and iliac fossa with middle age of 36 years old, especially in left
      retroperitoneum. Of the 20 cases, 18 tumors (90%) were hyaline vascular variants
      and 2 were mixed variants. There was no statistical difference in gender, age,
      tumor site and pathological subtype between two groups. (2) Retroperitoneal CD
      with PNP more likely complicated with bronchiolitis obliterans (BO) and high
      level of serum CEA/CA242. (3) Retroperitoneal Castleman tumors had clear margin,
      intact envelop and were easily resectable, however the biological behavior of CD
      with PNP might tend malignant changing, invade adjacent blood vessel or seed
      locally, and eventually relapse after operation. (4) The 5-year survival rate of
      retroperitoneal CD with PNP was 42.8%, significantly lower than those without
      PNP. The average survival time was 30 months. Bronchiolitis obliterans and
      radical resection were the key effect in prognosis of retroperitoneal CD.
      CONCLUSIONS: Retroperitoneal CD with PNP has distinctive clinical features. Early
      diagnosis, prompt removal of tumor and termination secretion of causative
      antibody are critical to the management of this disease.

PMID- 20137717
TI  - [Pathologic study of circumferential margin involvement in middle and lower
      rectal cancer].
AB  - OBJECTIVE: To study the rule of circumferential margin involvement (CMI) in
      middle and low rectal cancer and improve its detection rate. METHODS:
      Pathological large slices stained by HE method was combined with
      immunohistochemistry to study the CMI of 41 patients with middle and low rectal
      cancer. There were 20 female and 21 male patients, with an average age of 59.5
      years (range, 33 to 77 years). RESULTS: The positive rate of CMI by HE staining
      was 21.9%. The CMI positive rates of CK20, CDX2 and MMP7 by immunohistochemistry
      staining was 29.3%, 31.7% and 26.8%, respectively. The positive rate of CMI was
      36.6% when combined both HE and immunohistochemistry test, which was
      significantly higher than those in single methods (all P < 0.05). The positive
      rate of CMI in poorly differentiated tumor was significantly higher than that in
      moderately and well-differentiated tumor. The positive rate of CMI in the tumors
      with a distance of less than 5 cm between the anal verge and the lower tumor
      margin was significantly higher than that in tumors with the above-mentioned
      distances of greater than or equal to 5 cm (P < 0.05). According to MMP7
      detection, the positive rate of CMI in the group without lymphatic metastasis was
      significantly lower than that in N1 and N2 group (all P < 0.05). There was no
      significant correlation between CMI and gender, age, tumor infiltration,
      lymphatic metastasis, general pathological types and operation methods (P >
      0.05). CONCLUSIONS: The positive detection rate of CMI can be improved when
      combined large slices HE staining and immunohistochemistry. There is significant
      association between CMI and poorly differentiated tumor, lower location and
      positive lymphatic metastasis.

PMID- 20137718
TI  - [Value of combining 64 multi-slice spiral computer tomography and serum amyloid A
      protein in surgical decision-making in rectal cancer].
AB  - OBJECTIVE: To determine the accuracy and clinical value of combining 64 multi
      slice spiral computer tomography (MSCT) and serum amyloid A protein (SAA) in the
      preoperative staging of rectal cancer. METHODS: Prospectively enrolled patients
      with rectal cancer from October 2007 to October 2008. The patients were randomly
      assigned into two groups: MSCT and SAA combined group: both MSCT and SAA
      combinative assessment were performed for preoperative evaluation; MSCT group:
      only MSCT was performed preoperatively for tumor staging. The accuracy of the
      preoperative T, N, M, and TNM staging and the concordance rate of predictive
      operative strategy were compared between the two groups. RESULTS: Total of 225
      cases with rectal cancer were enrolled in this study. There were 110 cases in
      MSCT and SAA combined group and 115 cases in MSCT group. The baseline
      characteristics was comparable between the two groups. For MSCT and SAA combined
      group, the accuracies of preoperative staging of T, N, M and TNM was 87.3%,
      85.2%, 100% and 86.4%, respectively; and for MSCT group, the corresponding rates
      was 85.2%, 67.0%, 100% and 66.1%, respectively. Statistical differences was found
      in the accuracy of preoperative N and TNM staging between the two groups (P =
      0.009 and 0.001, respectively). In addition, there was statistical difference in
      the accuracy of prediction to operative procedures between the two groups (94.7%
      vs. 81.7%, P = 0.003). CONCLUSION: Combinative assessment of MSCT and SAA could
      improve the accuracy of preoperative staging, and thus provide higher predictive
      coincidence rate of operative procedures.

PMID- 20137719
TI  - [Analysis of relative factors of restenosis after artificially grafting bypasses
      on chronic ischemia of lower extremities].
AB  - OBJECTIVE: To analyze the relative factors of early-term restenosis after
      artificially grafting bypasses on chronic ischemia of lower extremities. METHODS:
      From January 2006 to September 2007, 40 cases suffered from chronic ischemia of
      lower extremities were treated by single side femoropopliteal bypass were
      followed up during 6 months after operation. There were 36 male and 4 case female
      with a mean age of (66 +/- 9) years old. Lipid, fibrinogen (FIB) and
      hypersensitive C reactive protein (hsCRP) were chemical examined during peri
      operation. Basing on the degree of restenosis in vascular anastomosis by Color
      Doppler graft scan, all the patients were divided into light, moderate and severe
      groups, respectively. Biochemical indicators and cytokines were investigated such
      as lipid, FIB, hsCRP, IL-6, transforming growing factor beta1 (TGF-beta1).
      Possible risk factors resulting in restenosis were compared statistically among
      three groups with SPSS 15.0. RESULTS: Restenosis were more severe among the
      patients with concomitance disease such as diabetes mellitus and smoking after
      operation. Relative risk were 6.47 and 7.92, respectively. There are significant
      difference in total cholesterin, low density lipoprotein, FIB, hsCRP, IL-6 and
      TGF-beta1 among three groups during six months after operation (P < 0.05).
      Multiple linear regression showed that FIB and TGF-beta1 may be the risk factors
      to intimal hyperplasia. CONCLUSION: Diabetes mellitus, smoking and higher levels
      of FIB may be the major high risk factors resulting in neointima hyperplasia and
      anastomosis restenosis.

PMID- 20137720
TI  - [Assessment of early mortality risk factors undergoing coronary artery bypass
      graft surgery].
AB  - OBJECTIVE: To analyze early mortality risk factors and clinical characteristics
      in our patients undergoing coronary artery bypass graft (CABG) surgery. METHODS:
      Clinical data of 310 consecutive patients undergoing CABG from January 2005 to
      March 2007 were collected. Twenty-two risk factors were evaluated by univariate
      and multivariate Logistic stepwise regression analysis. RESULTS: Univariate
      statistical analysis revealed that factors significantly correlated with early
      death were 12 variables including age, diabetes, neurological dysfunction, old
      myocardial infarction, acute myocardial infarction, ejection function, left main
      artery stenosis, emergency procedure, cardiopulmonary bypass time, aortic cross
      calming time, and mechanical ventilation time. Logistic stepwise regression
      analysis showed that emergency procedure, ejection function, age, cardiopulmonary
      bypass time, and mechanical ventilation time were independent risk factor of
      early mortality after procedure. CONCLUSION: Emergency procedure, ejection
      function, age, cardiopulmonary bypass time, and mechanical ventilation time are
      independent risk factors of early mortality after CABG procedure.

PMID- 20137721
TI  - [Surgical treatment of renal stenosis: a report of 80 cases].
AB  - OBJECTIVE: To evaluate the curative effect of surgical treatment for renal
      stenosis. METHODS: Eighty cases from November 1997 to August 2008 were reviewed,
      including 53 males and 27 females, aged from 9 to 80 years old. There are 42
      atherosclerosis, 23 Takayasu arteritis and 11 fibrodysplasia patients. Surgical
      procedures included aorto-renal bypass for 13 cases, autogenous renal
      transplantation for 5 cases, nephrectomy for 1 case, renal endarterectomy for 1
      case, lesion resection and reconstruction for 1 case, balloon angioplasty for 14
      cases, and stent implantation 48 cases. RESULTS: There were 1 mortality peri
      operation. During follow-up (1 to 129 months), 2 among 63 patients died.
      Significant decline of blood pressure [(135.7 +/- 15.8)/(80.1 +/- 8.5) mm Hg (1
      mm Hg = 0.133 kPa) vs. (149.8 +/- 18.3)/(88 +/- 13.6) mm Hg, P < 0.01] and
      totally 65.6% effective rate were observed. Atherosclerosis, Takayasu arteritis
      and fibrodysplasia group all presented positive anti-hypertension results with
      50%, 73.3% and 100% effective rate respectively (P < 0.05). The creatine level
      also underwent significant decrease [(112.7 +/- 53.6) micromol/L vs. (131.7 +/-
      91.7) micromol/L, P < 0.05], mainly in atherosclerosis group [(127.2 +/- 56.6)
      micromol/L vs. (138.0 +/- 87.0) micromol/L, P < 0.05]. CONCLUSIONS: Surgical
      treatment of renal stenosis can achieve improvement in hypertension and renal
      function. Endovascular stent and angioplasty are the first choices for
      atherosclerotic and fibrodysplasia patients respectively, while open surgery is
      better for Takayasu arteritis ones.

PMID- 20137722
TI  - [Single-port transumbilical laparoscopic nephrectomy: initial clinical experience
      of 3 cases].
AB  - OBJECTIVE: To evaluate the safety and efficacy of single-port transumbilical
      laparoscopic nephrectomy. METHODS: From December 2008 to August 2009, we have
      performed three cases of single-port transumbilical laparoscopic nephrectomy of
      nonfunctioning renal by Tri-Port system. Among three patients there were two
      cases of UPJO and one case of upper ureteral obstruction. Involved kidneys were
      not visualized in IVU and the GFR were not more than 0.90 ml/s. Tri-Port system
      was inserted transperitoneal through a 2 cm umbilical incision. The flexible
      grasper, scissors were used in addition to standard laparoscopic equipment. Renal
      pedicle was divided by Endoscopic Linear Stapling device. Specimens were
      extracted through the incision. RESULTS: The first and second case were
      successful, and the operation time were 85 min and 165 min. The bleeding volume
      were 50 ml and 100 ml. The discharge time after operation was 3 days and 5 days,
      respectively. The third case was converted to open surgery because of the edema
      and adhesion of renal pedicle. At 3 weeks of follow-up, the incisions were hidden
      in the umbilicus with good cosmetic benefit. CONCLUSIONS: This new method is
      technically feasible, which combined with these advantages of less trauma and
      more cosmetic benefit. However, more special instruments and long learning
      curving may be needed for those surgeons, who are going to carry out it.

PMID- 20137723
TI  - [The survival analysis of the advanced metastatic castration-resistant prostate
      cancer].
AB  - OBJECTIVE: To analyze predictive factors of advanced metastatic castration
      resistant prostate cancer. METHODS: From December 1996 to March 2008, 250 cases
      of advanced metastatic prostate cancer progressed into the stage of hormonal
      independent prostate cancer. The last follow-up date was 31 March 2008 and the
      median follow-up time was 24 months. During the follow-up, 131 cases were alive,
      105 cases were dead and 14 cases were lost to follow-up. Clinical and
      pathological information of the cases was analyzed to find the predictive factors
      that related to the prognosis. RESULTS: The median survival time of advanced
      metastatic castration-resistant prostate cancer was 30 months, and the one-year,
      two-year, three-year survival rate was 79%, 59%, and 41%. The univariate analysis
      indicated that prostate specific antigen (PSA) at diagnosis, clinical stage, the
      PSA nadir during hormonal therapy, the time form the start of hormonal therapy to
      the PSA nadir, the time of response duration during hormonal therapy, PSA
      velocity (PSAV) and PSA doubling time (PSADT) at the emergency of castration
      resistant prostate cancer, age and PSA at the diagnosis of castration-resistant
      prostate cancer were factors that predicted the survival time of advanced
      metastatic castration-resistant prostate cancer. The multivariate analysis
      indicated that the PSA nadir during hormonal therapy, the time form the start of
      hormonal therapy to the PSA nadir, PSAV at the emergency of castration-resistant
      prostate cancer, the time of response duration during hormonal therapy were
      independent factors that predicted the survival time of advanced metastatic
      castration-resistant prostate cancer. CONCLUSION: The PSA nadir during hormonal
      therapy, the time form the start of hormonal therapy to the PSA nadir, PSAV at
      the emergency of castration-resistant prostate cancer and the time of response
      duration during hormonal therapy are independent factors that predict the
      survival time of advanced metastatic castration-resistant prostate cancer.

PMID- 20137724
TI  - [Motor evoked potential of both upper extremities long term after anatomical
      hemispherectomy].
AB  - OBJECTIVE: To explore the function and motor pathway of remained cerebral
      hemisphere by studying motor evoked potential of both upper extremities on
      patients long term after anatomical hemispherectomy. METHODS: Five patients after
      anatomical hemispherectomy, who were marked 5 dispersive sites on head to perform
      transcranial magnetic stimulation. Recording motor evoked potential of target
      muscles (brachioradialis muscle and abductor pollicis brevis) of both upper
      extremities respectively when muscle resting and contracting. RESULTS: Only
      affected abductor pollicis brevis of case 2 and only affected brachioradialis
      muscle of case 4 and 5 recorded motor evoked potential when muscle resting. Motor
      evoked potential of some cases can be recorded simultaneously in homonymous
      muscles of both sides when muscle resting or contracting. CONCLUSIONS: There
      exists motor cortex that controls movement of ipsilateral limbs and also
      ipsilateral motor pathway of corticospinal connection at patients after
      anatomical hemispherectomy. It also means that the motor function of affected
      limbs has potency to recover well after hemispherectomy. The mirror movement
      after hemispherectomy is possible relate to overlap of both limbs' motor cortex.

PMID- 20137725
TI  - [The surgical treatment of metastatic periacetabular tumors].
AB  - OBJECTIVE: To retrospectively review the experience with different surgical
      procedures for periacetabular metastasis. METHODS: The data of 43 patients with
      periacetabular metastasis between July 2000 and July 2007 was reviewed. There
      were 21 patients with primary malignant tumors at the beginning, and 10 patients
      diagnosed metastasis by preoperative biopsy. The other 12 patients presented
      skeletal involved as initial manifestations of metastasis prior to the
      pathological diagnosis of the primary tumor. Twelve patients had solitary
      metastasis, and the others had multiple bone metastasis. The surgical procedure
      included curettage (35 cases) and en-blot excision (8 cases). The techniques of
      reconstruction of acetabular defect included total hip replacement (THR) with
      cemented components or titanium acetabular reconstruction cup (12 cases), THR
      with partial pelvis replacement with Candal Hook (16 cases), THR with Steinmann
      pins and cement augmented or titanium cup reconstruction (7 cases), and modular
      hemipelvic prosthesis reconstruction (8 cases). RESULTS: All the patients
      received successful operations. The average score for preoperative pain of 7.2
      was assessed. Forty-one patients (95.4%) were evaluated for relief of pain and
      resumption of walking, and the pain score improved to 3.5 after surgery. The
      average functional score was 24.5 postoperatively. Six of 32 patients had local
      recurrence. Fourteen patients died of diseases. The average blood loss during the
      operation was 1600 ml in 43 patients and the bleeding exceeded 3000 ml was in 3
      patients with renal carcinomas. Major complications included two superficial
      wound infections, one multiple organ failure and two dislocations. CONCLUSIONS:
      Although surgery will not typically cure patients of their metastatic disease,
      surgery that is well planned and well executed can help many people by relieving
      their suffering and improving their quality of life.

PMID- 20137726
TI  - [Outcomes of posterior C(1-2) fusion for atlantoaxial instability or dislocation
      using pedicle screws of atlas and axis].
AB  - OBJECTIVE: To retrospectively analyze and evaluate the results of treatment for
      atlantoaxial instability or dislocation employing pedicle screws of atlas and
      axis. METHODS: Thirty-one patients (23 male and 8 female) with atlantoaxial
      instability or dislocation were stabilized using pedicle screws of atlas and axis
      between May 2005 to January 2008. The patients ranged in age from 17 to 67 years
      (mean 43.5 years). Patients consisted of chronic odontoid fracture in 17, Os
      odontoideum in 8, fresh odontoid fracture in 4, transverse ligament rupture in 1,
      rheumatoid arthritis in 1. Clinical features included neck pain in 31; restricted
      neck movement in 28, varying degrees of spastic quadriparesis in 19. All patients
      underwent posterior C(1) to C(2) pedicle screw fixation. Operative time,
      intraoperative blood loss, complications were recorded, neurological and
      radiographic studies were carried. RESULTS: Mean follow-up time was 13 months.
      Operative time averaged 2.5 h. Mean intraoperative blood loss was 300 ml. A
      patient had postoperative wound infection and was treated conservatively with
      antibiotics and local wound care. A patient developed pulmonary artery embolism
      and got well with anticoagulation. Satisfactory stability was achieved in all
      cases with no vascular and C(2) neuralgia. Average JOA score in 19 cases
      increased at final follow-up (P < 0.01). Solid fusion was achieved in 29 cases,
      fusion rate was 93.6%. CONCLUSIONS: Stabilization of atlantoaxial complex via
      pedicle screws of atlas and axis has advantages of intraoperative restoration,
      easier placement of screw, solid fixation. It is a safe and effective treatment
      modality for posterior C(1-2) fusion.

PMID- 20137727
TI  - [Misplacement patterns of the pedicle screws in surgical correction of patients
      with adolescent idiopathic scoliosis].
AB  - OBJECTIVE: To evaluate and analyze the misplacement patterns of the pedicle
      screws in surgical correction of patients with adolescent idiopathic scoliosis.
      METHODS: For this study, 70 consecutive cases of patients with adolescent
      idiopathic scoliosis treated by posterior instrumented spinal fusion with pedicle
      screws were investigated from July 2008 to September 2008. Postoperative CT scans
      were performed in all cases. The patients included 58 girls and 12 boys, with a
      mean age of 14.5 +/- 2.7 years at surgery (range 12 - 19 years). Pedicle screws
      were inserted using anatomic landmark with free hand technique. A number of
      parameters were measured using PacsClient software (PACS) on workstation, which
      included distances of the penetration of medial, lateral pedicle cortex and
      anterior vertebral cortex. The distance between edge of aorta and tip of screw
      should be measured if left pedicle screw penetrated lateral pedicle cortex or
      anterior vertebral cortex. Misplacement screws with > 2 mm of either pedicular
      cortex perforation and grievous screws with >4 mm of medial pedicle perforation
      or contour of aorta were defined. The influencing factors for misplacement screws
      were analyzed. RESULTS: A total of 1030 pedicle screws were inserted, 773 in
      thoracic pedicle and 257 in lumbar pedicle. There were 108 (10.5%) misplacement
      screws, 35 of which penetrated lateral pedicle cortex, 56 of which penetrated
      medial pedicle cortex, 33 of which penetrated vertebral anterior cortex.
      Misplacement screw rate of apical vertebra, 5 segments above apical vertebra (AV
      5s) and 4 segments below apical vertebra (AV + 4s) were higher than other levels.
      Most of grievous screws were placed in apical vertebra region. CONCLUSIONS: The
      risk factors for misplacement screws included Cobb angle > 90 degrees and
      vertebrae rotation extent up to III-IV. Care should be exercised during pedicle
      screw instrumentation in the apical region of the main thoracic curve, AV-5s
      region and AV + 4s region.

PMID- 20137728
TI  - [Association between matrilin-1 gene polymorphism and bracing effectiveness in
      adolescent idiopathic scoliosis girls].
AB  - OBJECTIVES: To investigate the association between matrilin-1 gene polymorphism
      and bracing effectiveness in adolescent idiopathic scoliosis girls. METHODS: In a
      prospective study, AIS girls treated with standard bracing from January 2005 to
      December 2008 were included and followed up. All subjects of the study met the
      following criteria: female; skeletally immature (Risser sign grade 0 - 3); before
      menarche or < 1.5 years after menarche; Cobb angle 20 degrees - 40 degrees ;
      scoliosis caused by congenital, neuromuscular and other cause were excluded; no
      evidence of bone diseases, metabolic diseases or other condition known to affect
      bone metabolism; no history of bracing before onset; follow-up with an interval
      of 3 months, and total follow-up time > 2 years. Subjects met one of the
      following conditions was excluded: the final follow-up time < 2 years; bad
      compliance (ratio of the actual daily wearing time to proposed wearing time) of
      bracing (< 75%); change of bracing without doctor's order. Cobb angle of major
      curve was recorded before the bracing initiation and at the final follow-up. A
      progression of 6 degrees or more was considered to be a failure of bracing. The
      rs1149048 polymorphism in promoter of matrilin-1 gene was chosen for genotyping
      by PCR-RFLP method. Differences in age at initial visit, Risser sign, Cobb angle
      and genotype distribution were compared between brace failure and brace success
      groups. RESULTS: Seventy seven patients with AIS were included, with a mean age
      at (13.0 +/- 1.5) years and a mean Cobb angle at (30.3 +/- 11.9) degrees . After
      an average duration of 2.6 years follow-up, mean Cobb angle was 30.3 degrees +/-
      11.9 degrees . There were 19 cases (24.7%) in bracing failure and 58 cases
      (75.3%) in bracing success. The initial Cobb angle was larger in bracing failure
      group compared with bracing success group (P > 0.05). Patients with double major
      curve were found to have the lowest bracing failure rate (19.4%), but there was
      no significant difference compared with other curve patterns. Bracing failure
      rate was marked higher in individual with genotype GG (66.7%) than that with
      genotype AA or AG. CONCLUSIONS: Progression of most mild or moderate AIS can be
      managed by early standardized bracing treatment. It is shown that large initial
      Cobb angle and genotype GG of matrilin-1 gene are indicative of less bracing
      effectiveness.

PMID- 20137729
TI  - [Increased expression of Abi1 in hepatocellular carcinoma and its correlation
      with poor prognosis of hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the expression of Abi1 in hepatocellular carcinoma
      (HCC) and the correlation between its expression level and clinical pathological
      characteristics as well as prognosis of HCC. METHODS: Abi1 expression was
      determined at both mRNA and protein levels in 40 HCC tissues and their
      corresponding para carcinomatous liver tissues by RT-PCR and
      immunohistochemistry. The correlations between Abi1 expression levels and
      pathological characteristics as well as prognosis were also analyzed. RESULTS:
      The expression level of Abi1 mRNA in HCC tissues were significantly higher than
      those in corresponding para carcinomatous liver tissue (P < 0.05), and the
      expression level of Abi1 mRNA in nodular HCC tissues were also significantly
      higher than those in solitary large HCC tissues. Immunohistochemistry results
      showed that Abi1 protein located in cytoplasm of HCC cells and the expression
      level of Abi1 protein were significant positive correlated with the number of
      HCC, capsular formation, venous invasion and Edmondson-Steiner grade (P < 0.05).
      Combined with follow-up data, the results also showed that HCC patients with high
      Abi1 protein expression had a higher risk of invasion/metastasis and a shorter
      survival than those with low Abi1 protein expression (P < 0.05). CONCLUSIONS:
      Expression level of Abi1 is up-regulated in HCC tissues compared with
      corresponding para carcinomatous liver tissue and the expression level of Abi1 is
      significantly correlated with the number of tumor, capsular formation, venous
      invasion, Edmondson-Steiner grade and prognosis of HCC.

PMID- 20137730
TI  - [Effect of diabetes control after small intestine exclusion surgery in Goto
      Kakizaki rat with non-obese type 2 diabetes mellitus].
AB  - OBJECTIVE: To evaluate the effect and possible mechanisms of diabetes control
      after small intestine exclusion surgery in Goto-Kakizaki (GK) rat with non-obese
      type 2 diabetes mellitus. METHODS: Forty GK rats with non-obese type 2 diabetes
      mellitus underwent duodenal bypass (Group A, n = 8), which creates a shortcut for
      ingested nutrients bypassing duodenum alone; duodenal-jejunal bypass (Group B, n
      = 8), a stomach-preserving RYGB that excludes the duodenum and proximal jejunum;
      duodenum and total jejunum exclusion (Group C, n = 8); sub-total small intestine
      exclusion (Group D, n = 8), which creates a shortcut for ingested nutrients
      bypassing duodenum, jejunum and sub-total ileum; controls were pair-fed (PF) sham
      operated and untreated GK rats (Group SO, n = 8). The rats were observed for 24
      weeks after surgery. Body weight, food intake and fasting blood glucose level
      were tested at 0, 1, 3, 6, 12, 24 weeks after the operation in those groups. The
      concentrations of insulin and glucagon-like peptide-1 (GLP-1) concentrations were
      measured before (baseline) and then 30, 60, 120, and 180 minutes after OGTT at 0,
      12, 24 weeks after the operation. RESULTS: Mean operating time of all groups was
      similar. The mean body weight and food intake decreased significantly at 1 week
      after surgery (P < 0.01) and with no differences among the groups. Fasting blood
      glucose level decreased significantly after surgery in all the operation groups
      through the entire follow-up period (P < 0.05). No significant changes in fasting
      blood glucose level in SO group was found in 12 weeks after the operation, and it
      increased at 12 and 24 weeks after. Fasting blood glucose levels in group B
      decreased significantly compared with group A (P < 0.05), but no difference was
      found among group B, C and D (P > 0.05). Oral glucose-stimulated peak (30 min)
      levels of blood insulin and GLP-1 increased markedly in operation groups (A, B, C
      and D) after surgery (P < 0.01). Compared with group A, peak levels of blood
      insulin and GLP-1 in group B were strikingly higher (P < 0.05), but no difference
      was found when compared with group C or D (P > 0.05). CONCLUSIONS: In
      spontaneously non-obese type 2 diabetes mellitus rats, small intestinal exclusion
      including proximal gut is effective in terms of glucose control and has no direct
      relation with body weight and food intake loss. Restoration of the first-phase
      insulin secretion and high secretion of GLP-1 in type 2 diabetic subjects after
      gastrointestinal bypass surgery seem to be helpful to diabetes control. Taking
      intestinal nutrient absorption into consideration, duodenal-jejunal bypass may be
      a better surgery for diabetes control.

PMID- 20137731
TI  - [The effect of the different immunosuppression therapy on CD4(+)Foxp3(+) Treg
      cells in kidney recipients].
AB  - OBJECTIVE: To investigate the effect of the different immunosuppression therapy
      on CD4(+)Foxp3(+)regulatory T cells (CD4(+)Foxp3(+)Treg cells) in the peripheral
      blood monocytes of kidney transplantation recipients. METHODS: A Closed Cohort
      study was conducted in 50 primary living kidney transplant recipients between
      January 2006 and January 2008, who had been followed up for 1 year. The
      recipients divided into calcineurin inhibitors group (CNI + MMF + Pred) (19
      recipients, including cyclosporin group 10 recipients and tacrolimus group 9
      recipients), rapamycin group (RAPA + MMF + Pred) (31 recipients). Twenty end
      stage renal disease patients were in control group. The frequency of
      CD4(+)Foxp3(+)Treg cells in total CD4(+)T cells was analyzed by flow cytometry in
      peripheral blood from three groups, results were compared. RESULTS: The clinical
      variables of recipients such as age, sex, cold ischemia time, human leucocyte
      antigen mismatch, panel reaction antibody, rejection episode were no significant
      difference. The percentage of CD4(+)Foxp3(+)Treg cells in total CD4(+) cells was
      significantly higher in rapamycin group and end-stage renal disease group than
      calcineurin inhibitors group (P < 0.01). The level of CD4(+)Foxp3(+)Treg cells
      between cyclosporin group and tacrolimus group was no significant difference (P >
      0.05). CONCLUSION: The level of CD4(+)Foxp3(+)Treg was significantly higher in
      patients receiving RAPA + MMF + Pred than the patients receiving CNI + MMF +
      Pred, which suggested that RAPA may be play a more important role in immune
      tolerance induction.

PMID- 20137732
TI  - Propylene glycol dermatitis in the printing industry: the fundamental role of a
      workplace visit.
AB  - Workers in the printing industry serve as an example of a working population that
      is at high risk of developing occupational skin disease. Daily exposures include
      both irritants and sensitizing agents. While many substances have been associated
      with occupational contact dermatitis in this population, no detailed cases of
      allergic contact dermatitis (ACD) from propylene glycol (PG) have been reported
      to date. We present a case of a printing tradesman who developed work-related ACD
      from PG and who was subsequently able to return to work after a multidisciplinary
      team assessment that included a comprehensive worksite visit by a clinical
      occupational hygienist.

PMID- 20137733
TI  - Occupational allergic contact dermatitis due to thioureas.
AB  - Thioureas are used as additives in rubber products and as antidegradants for
      natural rubber latex. They are an uncommon cause of allergic contact dermatitis.
      This case represents an example of occupational allergic contact dermatitis
      solely from thioureas in rubber products and no cross-reactivity with other
      rubber allergens. Standard patch tests may fail to detect thiourea-induced
      allergic contact dermatitis, so clinicians should consider thiourea sensitization
      in rubber allergy.

PMID- 20137735
TI  - Neomycin.

PMID- 20137736
TI  - Local lymph node data for the evaluation of skin sensitization alternatives: a
      second compilation.
AB  - BACKGROUND: Development, evaluation and validation of alternatives to skin
      sensitisation testing require the availability of reliable databases with which
      comparative analyses can be conducted to establish performance characteristics.
      To facilitate this we have published previously a database comprising results
      from local lymph node assays (LLNAs) conducted with 211 chemicals. That database
      embraced a substantial range of chemistry, and of relative skin sensitising
      potency, and has found application in the assessment of new or refined methods.
      OBJECTIVE: In this paper we describe a second compilation to extend the LLNA
      database. METHODS: This second data compilation was derived from previously
      conducted LLNA studies involving an additional 108 chemicals. In addition, the
      first database contained a small number of inaccuracies, affecting results
      recorded with a few chemicals. In this paper these have been corrected. RESULTS:
      The inclusion of 108 new substances has served to extend and consolidate the
      areas of chemistry covered by the database. In addition, the entire dataset was
      evaluated for pre and prohaptens which will facilitate the choice of chemicals
      for alternative assay developments. CONCLUSIONS: It is anticipated that the new
      revised and extended database totalling over 300 chemicals will now serve as the
      primary resource to support the development and evaluation of new approaches to
      hazard identification and potency assessment.

PMID- 20137737
TI  - An 8-year retrospective review of patch testing with rubber allergens: the Mayo
      Clinic experience.
AB  - BACKGROUND: Allergic contact dermatitis from rubber chemicals is increasingly
      recognized. OBJECTIVE: To review the results of patch testing with rubber
      allergens from January 1, 2000, through December 31, 2007. METHODS: Patients who
      underwent patch testing with a specialized series of rubber allergens were
      identified. RESULTS: In total, 773 patients (64.2% female; mean age, 48.6 years)
      were patch-tested with a rubber series (27 allergens), and 739 (95.6%) were
      concomitantly patch-tested with a standard allergen series. Commonly affected
      sites of dermatitis were the hand (49.7%), foot (15.9%), leg (12.0%), and arm
      (10.9%). The most common occupations were health care worker (16.3%) and
      homemaker (6.5%); 11.3% were retired. The rate of allergic reaction to at least
      one rubber allergen was 245 of 773 (31.7%). The allergens that most commonly
      yielded positive reactions were 4,4-dithiodimorpholine 1% (28/286 [9.8%]),
      thiuram mix (56/739 [7.6%]), and diphenylguanidine 1% (57/759 [7.5%]).
      CONCLUSION: Rubber is a frequent cause of allergic contact dermatitis. Patch
      testing with a rubber series improved the ability to diagnose allergic contact
      dermatitis caused by rubber.

PMID- 20137738
TI  - In vitro human skin penetration of geraniol and citronellol.
AB  - BACKGROUND: Geraniol and citronellol are commonly used fragrance components in
      consumer products. Both are listed as alleged fragrance allergens that should be
      declared in the European Union when used in cosmetics and consumer products. Such
      allergenic potential is determined largely by effects on the skin once these
      materials penetrate and elicit an immune response. Few data demonstrate their
      penetration abilities or their effects on percutaneous absorption. We wanted to
      determine the effects of these materials on skin absorption. Skin penetration
      characterization via flow-through diffusion study serves as a reasonable model
      for determining dermal dosing for fragrance materials. Such characterization can
      be used for more accurate safety exposure calculations and regulatory
      determinations. Extensive comparisons to in vivo data in humans or closely
      related animals will be required before accepting flow-through diffusion methods
      as in vivo alternatives by industry and regulatory bodies. OBJECTIVE: To evaluate
      the penetration abilities of geraniol and citronellol when they are used in a
      typical vehicle in consumer products. METHODS: In vitro skin penetration of
      radiolabeled geraniol and citronellol was studied under occlusion in human
      cadaver skin, using flow-through diffusion cells for scintillation counting to
      determine the percentage of dose absorbed. For comparison, two doses of each
      material were used: 2% and 5% in 3:1 diethyl phthalate/ethanol. RESULTS: After 24
      hours, geraniol and citronellol had relatively low skin absorption rates; 3.8% +/
      2.1% of 2% citronellol, 4.7% +/- 1.9% of 5% citronellol, 3.5% +/- 1.9% of 2%
      geraniol, and 7.3% +/- 1.1% of 5% geraniol were recovered from skin and receptor
      fluid compartments. These materials showed good mass-balance recovery. The
      majority of the dose was recovered in the skin washes (a minimum of 64.7% +/-
      4.6% recovered for 2% citronellol and a maximum of 79.3% +/- 3.9% recovered for
      5% geraniol). Receptor fluid collection points over time showed a linear increase
      in the amounts of citronellol and geraniol that penetrated the skin, although
      overall absorption values were quite small. CONCLUSION: In vitro results indicate
      that geraniol and citronellol have low potentials for skin penetration, which has
      implications for their ability to induce allergenicity and for more predictive
      toxicologic profiling of these materials. In vivo studies should be done to
      correlate the in vitro results.

PMID- 20137739
TI  - Patch testing with a textile dye mix and its constituents in a baseline series.
AB  - BACKGROUND: Among the textile dyes, disperse dyes are common sensitizers.
      OBJECTIVE: To investigate whether patch testing with a textile dye mix consisting
      of eight disperse dyes would be equivalent to testing with the separate
      ingredients of the mix at the concentrations used in the mix. METHODS:
      Researchers tested 1,780 consecutive patients with a mix consisting of Disperse
      Blue 35, Disperse Yellow 3, Disperse Orange 1, Disperse Orange 31 (mislabeled as
      Disperse Orange 3), Disperse Red 1 and 17, all at 0.5%, and Disperse Blue 106 and
      124, both at 0.1%, and with the ingredients at these concentrations. Testing with
      the labeled dyes at 1.0% was done on 500 of the patients and additionally on the
      remaining patients who reacted positively to the mix, any of the ingredients, p
      phenylenediamine, or black rubber mix. RESULTS: Thirty-five patients (2%) reacted
      to the mix, and 34 patients were allergic to at least one ingredient tested at
      the lower concentration. CONCLUSION: The textile dye mix was as good a detector
      of contact allergy to the disperse dyes as was testing with any combination of
      the ingredients at the concentration in the mix. Increasing the concentration of
      the ingredients of the textile dye mix might increase the sensitivity of the mix.

PMID- 20137740
TI  - Bisabolol.
AB  - Bisabolol is an active plant extract isolated from German chamomile and thought
      to have antiinflammatory and skin-soothing properties. It is a common additive in
      many products, including moisturizing creams and ointments, lotions, cleansers,
      sunscreens, antiperspirants, and makeup products. Contact dermatitis from
      bisabolol has been reported in Europe and is purported to occur in the United
      States. Patch testing with bisabolol-containing products or bisabolol may be
      useful in the work-up of patients with presumptive allergic contact dermatitis or
      potentially worsening atopic dermatitis. Patients sensitized to bisabolol should
      be counseled to avoid any bisabolol-containing products.

PMID- 20137741
TI  - Vulvar allergic contact dermatitis from clotrimazole.

PMID- 20137742
TI  - Allergic contact dermatitis from a permanent marker.

PMID- 20137743
TI  - Clinical and epidemiological aspects of subtypes of melanocytic nevi (Flat nevi,
      Miescher nevi, Unna nevi).
AB  - The term "melanocytic nevus" comprises a group of clinically and pathologically
      distinct subtypes. In this prospective clinical study we evaluated the frequency,
      localization, and age and gender distribution of flat nevi (FN), Miescher nevi
      (MN), and Unna nevi (UN) in a caucasian population. Nevi were counted in 400
      patients, of which 47 had a history of melanoma. Additionally, the patients
      answered to a detailed UV questionnaire. Flat nevi represented the most common
      type of melanocytic nevi, with a peak in the 3rd decade of life. They were mostly
      found on the extremities and on the trunk. Miescher nevi were most common in the
      6th decade and were predominantly found in the head and neck region. Unna nevi
      showed a maximum in the 8th decade and they were mainly situated on the trunk.
      The counts of all three nevus subtypes were elevated in the melanoma group. Our
      results confirm that FN, MN, and UN represent melanocytic nevi with distinctive
      morphological and clinical characteristics. The role of sunlight seems to be more
      prominent in the pathogenesis of FN. The precise description of FN, MN, and UN
      may serve as a base for a pathogenetic distinction of subtypes of melanocytic
      nevi in the future.

PMID- 20137744
TI  - Linear IgA bullous dermatosis: the more frequent bullous dermatosis of children.
AB  - BACKGROUND: Linear IgA bullous dermatosis (LAD) of children is relatively
      frequent in Africa. We undertook this study to evaluate the frequency of this
      disease among autoimmune bullous diseases (AIBD) in Tunisian children. METHODS:
      We present a 32-year retrospective study (January 1976 to December 2007).
      Children with chronic acquired bullous diseases seen at the Charles Nicolle
      Hospital of Tunis and for whom direct immunofluorescence (DIF) of the
      perilesional skin demonstrated linear IgA immunoglobulin deposits were included
      in the study population. RESULTS: Thirty-one children with LAD were collected
      representing 65.9 percent of all AIBD of children collected in the same period,
      with a mean age of 5.5 years and a sex ratio M/F of 2.4. Most of the children had
      a generalized eruption (28/31) but more profuse on the face, pelvic region,
      buttocks, and limbs. Mucosal lesions were present in only 4 children (12.9%). The
      mean duration of the disease was 14 months. Direct immunofluorescence
      demonstrated predominantly linear IgA deposits along the dermal-epidermal
      junction in all patients. Faint IgG, IgM, and complement were also seen (20/31).
      Indirect immunofluorescence was negative in 67 percent of cases. Eight patients
      responded to Dapsone, but prednisone had to be added in 7 children and
      erythromycin in 4 others to control the disease. A long term remission period (34
      months) was achieved in 61.9 percent of patients. CONCLUSION: This study confirms
      that LAD is the most common AIBD in children in Tunisia and it frequently occurs
      in preschool-aged males. Independently of the medication chosen for treatment, a
      long term remission is frequently observed.

PMID- 20137745
TI  - Patient safety in dermatology: a review of the literature.
AB  - OBJECTIVE: We performed a literature review of patient safety topics pertinent to
      dermatology and related to outpatient settings for situations in which data from
      dermatology are lacking. METHODS: Searches in MEDLINE via PubMed interface, OVID
      and Google Scholar were carried out from October, 2008 through May, 2009 for
      English-language articles published between 1948 and 2009. Each search combined 2
      or 3 of the following terms: patient safety, medical error, human error,
      preventable adverse event, dermatology, outpatient, ambulatory care, medication
      error, diagnostic error, laboratory error, pathology error, office-based surgery,
      wrong-site procedure, infections, falls, laser safety, scope of practice.
      Personal communications, websites, books, dermatology newsletters and major
      textbooks were also scrutinized. Potentially relevant articles and communications
      were critically evaluated by the authors. References from these articles were
      searched for "other relevant articles." SUMMARY: Patient safety studies in
      dermatology and outpatient settings are lagging behind those in inpatient
      settings. Systems changes are needed to reduce medical errors rather than
      penalize individual healthcare workers. Although technology may improve patient
      safety in numerous aspects, it introduces new sources of errors. CONCLUSION: Our
      review reveals few studies on dermatologic patient safety, supporting the
      pressing need for such studies and reports in the future.

PMID- 20137746
TI  - Topical delivery of active principles: the field of dermatological research.
AB  - To be effective an active drug or principle must cross the stratum corneum
      barrier; this process can be influenced to obtain better functional and
      therapeutical effects. In spite of the wide variety of the methods studied in
      order to improve the transdermal transfer to obtain systemic effects, the
      applicability is limited in this field. Attention to the epidermal barrier and
      penetration of active principles has been reported mostly in studies concerning
      dermocosmetics. Studies regarding methods of penetration are gaining experimental
      and clinical interest. Cutaneous bioavailability of most commercially available
      dermatological formulations is low. Increase of intradermal delivery can relate
      to chemical, biochemical, or physical manipulations. Chemical enhancers have been
      adopted to: (a) increase the diffusibility of the substance across the barrier;
      (b) increase product solubility in the vehicle; (c) improve the partition
      coefficient. Moreover methods of interference with the biosynthesis of some
      lipids allow the modification of the structure of the barrier to increase the
      penetration. The main physical techniques that increase cutaneous penetration of
      substances are: iontophoresis (that increases the penetration of ionized
      substances), electroporation (that electrically induces penetration through the
      barrier), and sonophoresis, based on 20 to 25 KHz ultrasound that induces
      alterations of the horny barrier, allowing penetration of active principles.
      Recent development of these methods are here reported and underline the
      importance and role of vehicles and other factors that determine effects of
      partition and diffusion, crucial to absorption.

PMID- 20137747
TI  - Patients are happy to be informed of their final non-melanoma skin cancer results
      by post.
AB  - During the past year, because of increasing pressure to see more patients, we
      have started to write to our patients informing them in a letter of their final
      skin cancer histology results following surgery for non-melanoma skin cancers:
      basal cell carcinoma and squamous cell carcinoma only. A questionnaire-based
      study was carried out to assess whether patients were happy to receive
      information concerning their non-melanoma skin cancer diagnosis in a carefully
      worded letter. One-hundred fifty patients were involved with a diagnosis of
      "completely excised non-melanoma skin cancer (NMSC)" that had previously received
      their final diagnosis by post. Seventy-seven (51.3%) patients responded to the
      questionnaire. Eighty-seven percent felt that they had been given the cancer
      diagnosis in an appropriate manner; 90 percent reported that they had understood
      the explanation about their skin cancer. In addition, 81 percent stated that they
      had been sufficiently involved in the discussion about their skin cancer and its
      treatment. Patients gave an average rating of 7.76 (1 = poor and 10 = excellent)
      for the overall experience of care that they had received. By writing to the
      patient with their final histology results, we have reduced the number of follow
      up appointments without reducing the quality of patient care.

PMID- 20137748
TI  - Verrucous plaque on the face: what is your diagnosis?
AB  - A 46-year-old male patient presented with hyperpigmented verrucous plaques and
      papules mainly on the left cheek and malar region that had evolved over a 7 month
      period. Histopathology demonstrated the presence of a large number of classical
      copper penny bodies or muriform bodies and a predominantly neutrophilic dermal
      infiltrate that confirmed the diagnosis of chromoblastomycosis.

PMID- 20137749
TI  - Cowden syndrome.
AB  - Mucocutaneous papillomas can be manifestations of an autosomal dominant condition
      known as Cowden syndrome (CS). We report the case of a 22-year-old man with oral
      and cutaneous papules and a past history of thyroid malignancy. It is important
      to recognize oral manifestations of CS; they can lead to early diagnosis of the
      condition.

PMID- 20137750
TI  - Type 2 segmental glomangiomas.
AB  - Glomangiomas of the skin, currently named glomuvenous malformations (GVMs), are
      benign vascular lesions composed of thin-walled distorted blood vessels,
      surrounded by variable rows of glomus cells. These cells resemble the modified
      smooth muscle cells of the normal glomus body. Glomuvenous malformations occur
      after both alleles of the gene encoding for glomulin, a molecule involved in
      smooth muscle cell differentiation, are hit by a loss-of-function mutation.
      Multiple GVMs are rare and often congenital, but they may also appear later in
      life. In this report we describe a 39-year-old man who developed unilateral
      segmental GVMs on his trunk in early childhood, with the histological features of
      glomangiomas. As several satellite lesions emerged at distant skin sites later in
      life, our case probably represents type 2 segmental GVMs, caused by localized
      loss of heterozygosity in an individual carrying a heterozygous germline mutation
      in the glomulin gene.

PMID- 20137751
TI  - A toddler with facial nodules: a case of idiopathic facial aseptic granuloma.
AB  - We describe the case of a 3-year-old boy who presented with several asymptomatic
      facial nodules present for six months. A skin biopsy obtained from the nodules
      showed a moderately well-defined granuloma in the superficial and deep dermis. A
      squamous epithelial lined cyst, extravasated keratin, or shadow cells were not
      identified. Bartonella henselae titers and the Coccidioidomycosis immitis
      immunodiffusion test were negative; a Tuberculin Skin Test was non-reactive.
      Fite, Periodic acid-Schiff (PAS) and Gomori-Grocott methenamine silver (GMS)
      stains failed to identify microorganisms. In addition, tissue cultures for
      bacteria, fungus, and acid fast bacilli were negative. In light of the clinical
      findings, histology, and negative cultures, a diagnosis of idiopathic facial
      aseptic granuloma (IFAG) was made. After the biopsy, the child was treated with
      erythromycin and clarithromycin, each for one month, and the lesions slowly
      improved.

PMID- 20137752
TI  - Perianal cutaneous malakoplakia in an immunocompetent patient.
AB  - Malakoplakia is an uncommon inflammatory condition usually affecting the
      genitourinary tract, which has been associated with infections, tumors, and
      immunocompromised states. The condition has been reported in many different
      organs and it may rarely involve the skin. We describe a case of an isolated
      perianal cutaneous malakoplakia in an immunocompetent 23-year-old Syrian male.

PMID- 20137753
TI  - Piebaldism and neurofibromatosis type 1: family report.
AB  - Piebaldism is a rare disorder present at birth and inherited as an autosomal
      dominant trait. It results from a mutation in the c-kit proto-oncogene and is
      associated with a defect in the migration and differentiation of melanoblasts
      from the neural crest. Clinical manifestations and phenotypic severity strongly
      correlates with the site of mutation within the KIT gene. Here we report a 3-year
      old boy and his 33-year-old father with leukoderma and poliosis associated with
      clinical criteria for Neurofibromatosis type 1. Genetic study of both revealed a
      p.Gly610Asp mutation in the KIT gene. This familiar mutation has not yet been
      reported in the literature. There are rare reports of piebaldism in association
      with neurofibromatosis type I.

PMID- 20137754
TI  - Bilateral retro-auricular milia en plaque: a case report and review of the
      literature.
AB  - Milia en plaque, a rare inflammatory plaque type of milia is generally located in
      the periauricular area. Bilateral retroauricular milia en plaque is very rarely
      reported. Here, we report another case of bilateral retroauricular milia en
      plaque and review the previous cases.

PMID- 20137755
TI  - Punctate porokeratotic keratoderma.
AB  - We report a 29-year-old woman with multiple small keratotic papules on her
      lateral fingers and first and second toes. Histopathology revealed a compact
      parakeratotic column with a poorly developed stratum granulosum, indicating
      punctate porokeratotic keratoderma (PPK). We discuss demographics, etiology,
      histopathology, differential diagnosis, and treatment of this disease.

PMID- 20137756
TI  - Infundibulomatosis: a case report with immunohistochemical study and literature
      review.
AB  - Tumor of the follicular infundibulum was first described in 1961 by Mehregan and
      Butler in a patient presenting with multiple papules. It is more frequent,
      however, as an isolated lesion affecting mainly the face, neck, and upper trunk.
      Clinical presentation is variable, requiring histology for the diagnosis, which
      reveals typically a plate-like proliferation of keratinocytes in continuity with
      the epidermis and hair follicles; some morphological features are reminiscent of
      the outer root sheath of the hair follicle. A well defined network of elastic
      fibers surrounding the tumor is usually present using the appropriate staining
      and this finding is specific because it is not found in other benign follicular
      tumors. Multiple infundibulomas are usually sporadic and there is no apparent
      association with internal malignancy. The authors report the case of a 30-year
      old female patient with a 5-year history of multiple small discrete hypopigmented
      macules and papules, scattered over the submental and submaxillary regions and
      anterior neck. Histopathological findings were consistent with the diagnosis of
      tumor of the follicular infundibulum. Immunohistochemical study was performed to
      further characterize the proliferation.

PMID- 20137757
TI  - Case report: Prolonged collodion membrane causing constrictive bands of the
      digits and treatment.
AB  - Collodion babies present unique diagnostic and management challenges. We describe
      a 2-month-old female with lamellar ichthyosis and prolonged collodion membrane
      with two constrictive bands of the fingers causing significant erythema, edema,
      and pain. We suggest prompt release of these constrictive bands with an 11-blade
      and closely follow up of collodion babies until their membrane has fully
      desquamated.

PMID- 20137758
TI  - A review of the practices and results of the UTMB to South Pole teledermatology
      program over the past six years.
AB  - There is no place on earth more remote and inaccessible than Antarctica. In 2002,
      Raytheon Polar Services Co. (RPS) awarded The University of Texas Medical Branch
      (UTMB) at Galveston the contract to provide specialty medical services via
      telemedicine to the approximately 3,500 National Science Foundation (NSF)
      researchers and support personnel who rotate through Antarctica in a given year.
      We present the practices and results of the UTMB to the South Pole
      teledermatology program over the past six years, from 2003 to 2008. Issues
      encountered include logistics of sending out biopsies for pathologic diagnosis,
      limited bandwidth, and satellite availability for data transmission. The UTMB to
      the South Pole teledermatology program demonstrates the clinical practicality of
      telemedicine in providing dermatologic care to remote populations in extreme
      climate conditions.

PMID- 20137759
TI  - Important risk factors in melanoma from the Dermato-Oncologic Unit of Brescia,
      Italy.
AB  - One of the most significant risk factors for melanoma is a positive family
      history of the disease. It is estimated that approximately 10 percent of melanoma
      cases report a first-or second-degree relative with melanoma. We reported the
      experience of the Dermato-Oncologic Unit of Brescia, Italy.

PMID- 20137760
TI  - Significant discrepancy in cyclosporin A post-dose concentrations when analyzed
      with specific RIA and HPLC method.
AB  - C(2) or AUC sparse sampling methods are widely recommended for therapeutic
      monitoring of cyclosporin A (CsA). One additional reason for promoting the C(2)
      sampling time in place of commonly used C(0) is that the C(2) level may actually
      provide more accurate measurement of parent drug concentration by immunoassays,
      as lower portion of metabolites has been formed 2 hours post-dose than at the
      steady-state trough time point. HPLC and RIA whole blood levels of CsA and its
      main metabolites AM1, AM9 and AM4N were compared during 12 hours profile after
      chronic administration. 40 stable renal transplant male patients (age 49 +/- 6
      years, body weight 76 +/- 7 kg) were treated with CsA (Sandimmun Neoral, Novartis
      s.r.o, Prague, Czech Republic) in doses 198 +/- 56 mg twice daily. Samples were
      collected in steady state (after 2 weeks of regular treatment regimen) as
      follows: pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours after dose. CsA
      concentrations were determined both specific RIA assay (Cyclo-Trac SP Whole, Dia
      Sorin) and HPLC method, where concentrations of metabolites AM1, AM9 and AM4N
      were simultaneously analyzed. The AUC(0-12) was calculated by the linear
      trapezoidal rule. The percentage prediction error defined as [(RIA value-HPLC
      value)/HPLC value] x 100 was used for estimation of differences. C(max), t(max),
      and C(avg) were compared using Student's t-test. RIA produced significantly
      higher CsA levels than HPLC method in the period of 0.5 - 5 hours after
      application. The greatest differences (43 - 56%) occurred between 1 and 3 hours
      after dose. AUC(0-12), C(max) a C(avg) calculated from RIA results were
      consequently significantly higher. Only t(max) remained unchanged. The ratio of
      metabolites/parent drug after CsA intake is decreasing but their absolute
      concentrations are significantly increasing. Mean levels at C(0)/C(2) were CsA
      RIA 82/612, CsA-HPLC 89/425, AM1 121/179, AM9 4.1/81.4, AM4N 9.5/21.0 ng/ml. TDM
      using C(2) and AUC sparse sampling may cause misleading interpretation using both
      methods alternately for the same patient.

PMID- 20137761
TI  - Effect of cilostazol on platelet aggregation in patients with non-ST elevation
      acute coronary syndrome.
AB  - AIMS: The optimal antithrombotic regimen for non-ST elevation acute coronary
      syndrome(NSTEACS) has not yet been defined and the risk of ischemic events
      remains high in these patients. We aimed to evaluate the effect of cilostazol on
      agonist induced platelet aggregation and serum plasminogen activator inhibitor
      1(PAI-1) in the patients with NSTEACS administered along with the standard
      antiplatelet regimen. PATIENTS AND METHODS: 40 patients of NSTEACS presenting
      within 72 h of onset of symptoms were randomized to cilostazol or placebo in 1 :
      1 ratio, in whom a conservative treatment strategy was adopted. Cilostazol 100 mg
      b.i.d was administered within 12 h of hospital admission for 7 days along with
      standard doses of aspirin and clopidogrel. The primary end points were effect on
      agonist-induced platelet aggregation and serum PAI-1 levels after 7 days of
      treatment. Safety and clinical outcome assessment were also done at 7 and 30
      days. RESULTS: Patients in the triple therapy group showed significant decrease
      in the ADP (25.5 +/- 27.4 vs. 5.6 +/- 8.4; p = 0.003) and collagen (24.9 +/- 25.5
      vs. 11.7 +/- 11; p = 0.04) induced percentage platelet aggregation after 7 days
      of treatment compared to the dual therapy group. There was no significant change
      in levels of serum PAI-1 (50.30 +/- 10.17 ng/ml vs. 53.47 +/- 14.08 ng/ml; p =
      0.42). The composite of recurrent ischemia, myocardial infarction, need for
      intervention and death occurred in 4 patients in the cilostazol group compared to
      7 in the placebo group at the end of 30 days of follow-up (p = 0.48). CONCLUSION:
      Cilostazol has additional platelet aggregation inhibition action in patients with
      NSTEACS along with aspirin and clopidogrel.

PMID- 20137762
TI  - Sotrastaurin and everolimus pharmacokinetics after single-dose coadministration.
AB  - INTRODUCTION: Sotrastaurin is an immunosuppressant that blocks T-lymphocyte
      activation via protein kinase C inhibition. The authors determined whether a
      pharmacokinetic interaction occurs between sotrastaurin and everolimus, both of
      which are substrates and inhibitors of CYP3A4. METHODS: This was a randomized,
      three-period, crossover study in 18 healthy subjects. They received single oral
      doses of (1) 100 mg sotrastaurin, (2) 2 mg everolimus, and (3) the drug
      combination. Clinical and pharmacokinetic data were collected to Day 5 after each
      treatment. RESULTS: Coadministration of everolimus decreased sotrastaurin C(max)
      from 638 +/- 295 to 539 +/- 211 ng/ml yielding a combination/ monotherapy ratio
      (90% confidence interval) of 0.87 (0.76 - 1.00). Sotrastaurin total AUC was not
      altered by everolimus with values of 3660 +/- 1853 versus 3630 +/- 2006 ng*h/ml
      and a ratio of 1.00 (0.88 - 1.13). Sotrastaurin increased everolimus C(max) from
      15 +/- 6 to 16 +/- 6 ng/ml yielding a ratio of 1.15 (0.99 - 1.33) and increased
      everolimus total AUC from 114 +/- 50 to 137 +/- 56 ng*h/ml yielding a ratio of
      1.20 (1.05 - 1.37). The possibility that a higher dose of sotrastaurin than used
      in this study might further increase everolimus blood levels cannot be excluded.
      CONCLUSIONS: Coadministration of a single 100 mg dose sotrastaurin with a single
      2 mg dose everolimus did not alter sotrastaurin pharmacokinetics to a clinically
      relevant extent. Everolimus AUC was increased 20% by sotrastaurin.

PMID- 20137763
TI  - A novel microsatellite polymorphism of sodium channel beta1-subunit gene (SCN1B)
      may underlie abnormal cardiac excitation manifested by coved-type ST-elevation
      compatible with Brugada syndrome in Japanese.
AB  - OBJECTIVE: Brugada syndrome (BrS) is a rare sodium channelopathy typically seen
      in middle-aged, Southeast Asian males conferring high risks of cardiac sudden
      death. Loss-of-function mutations in SCN5A encoding the alpha-subunit of cardiac
      sodium channels may account partially for its etiology. We aimed to study whether
      mutations in the beta-subunits of sodium channel (SCN1B and SCN2B) would also be
      associated with abnormal cardiac excitation in BrS. METHODS: 85 Japanese patients
      suspected to have BrS undertook a diagnostic challenge test with a sodium channel
      blocker, pilsicainide. Genetic screenings were performed for SCN5A, SCN1B and
      SCN2B by PCR-SSCP and direct sequence of amplicons in the patients and 50 healthy
      controls. RESULTS: 30 patients exhibited BrS-like ECG pattern (i.e., a coved-type
      ST-segment elevation) either at baseline or after the drug challenge. Genetic
      screenings revealed a sequence variation (p.R190Q) and 3 polymorphisms (p.H558R,
      p.R1193Q, IVS24+53T > C) in SCN5A, a sequence variation (g.-26G > T) and 2
      polymorphisms (IVS1+53G > T and IVS3 +2996(TTA)8-15) in SCN1B and 2 polymorphisms
      (IVS2+27A > G, IVS2+76G > A) in SCN2B. A logistic analysis revealed that male,
      middle age (40 - 59 years of age) and IVS3+2996(TTA)8 of SCN1B were significantly
      (p < 0.05) associated with the development of BrS-like ECG pattern with odds
      ratios (95% confidence intervals) of 5.9 (1.8 - 19.6), 2.9 (1.4 - 6.1) and 2.3
      (1.1 - 4.9), respectively. While the IVS3+2996(TTA)8 allele has not been reported
      in Caucasians previously, its allelic frequency in the patients exhibiting the
      BrS-like ECG pattern (0.250) was comparable to that in the healthy controls
      (0.260). CONCLUSION: The IVS3+ 2996(TTA)8 allele commonly seen in Japanese would
      not be pathogenic itself but may render male, middle-aged Japanese more
      susceptible to BrS.

PMID- 20137764
TI  - The effect of food with varying fat content on the clinical pharmacokinetics of
      gabapentin after oral administration of gabapentin enacarbil.
AB  - Gabapentin enacarbil, an actively transported prodrug of gabapentin, provides
      sustained and dose-proportional exposure to gabapentin. OBJECTIVE: To evaluate
      the effect of food of varying fat content on the pharmacokinetics and
      tolerability of gabapentin enacarbil. METHODS, MATERIALS AND SUBJECTS: A
      randomized, open-label, crossover study of 1,200 mg gabapentin enacarbil was
      conducted in 12 healthy adults, under four conditions: fasted, or following low
      fat (200 - 300 kcal total, approximately 6% from fat), moderate-fat (500 - 600
      kcal total, approximately 30% from fat) or high-fat meals (1,000 kcal total,
      approximately 50% from fat), separated by a washout period of >or= 5 days.
      RESULTS: Ten subjects completed treatment under all four conditions. Data from
      all subjects were used for pharmacokinetic and safety analyses unless stated
      otherwise. Mean (standard deviation) bioavailability (based on urinary recovery)
      of gabapentin from gabapentin enacarbil was 42.0 (6.1)% (fasted), 64.3 (13.2)%
      (low-fat meal), 64.9 (16.9)% (moderate-fat meal), and 76.1 (14.4)% (high-fat
      meal). Gabapentin exposures (AUC(inf)) in fed conditions were 23% (low-fat meal),
      31% (moderate-fat meal), and 40% (high-fat meal) greater than the exposure under
      fasted condition. Fed conditions did not significantly delay median t(max), but a
      trend for delayed gabapentin enacarbil absorption was seen in t(max) ranges
      following moderate- and high-fat meals compared with the fasted state or low-fat
      meal. The most commonly reported treatment-emergent adverse events (TEAEs) were
      dizziness (4 subjects), balance disorder (4 subjects) and somnolence (3
      subjects). All TEAEs were rated as mild in intensity. CONCLUSION: Administration
      of gabapentin enacarbil with food enhanced gabapentin exposure compared with
      fasted conditions, regardless of the fat or caloric content, and gabapentin
      enacarbil was generally well tolerated.

PMID- 20137765
TI  - Comparison of one-year costs of type 2 diabetes treatment with insulin glargine
      or insulin detemir in a basal supported oral therapy (BOT) in Germany.
AB  - OBJECTIVE: A one-year cost analysis comparing basal insulin analogues glargine
      (IG, Lantus) versus detemir (ID, Levemir) in combination with oral antidiabetic
      drugs (basal supported oral therapy; BOT) in insulin naive Type 2 diabetes
      patients in Germany based on the results of a randomized controlled clinical
      trial (RCT). The trial demonstrated equivalent treatment efficacy. MATERIALS AND
      METHODS: Total direct diabetes treatment costs were estimated from the
      perspective of the German statutory health insurance (SHI) for the time horizon
      of one-year. Simulated resources included medication (insulin, oral antidiabetic
      drugs) and consumable items (needles, blood glucose test strips and lancets).
      Initial and final insulin doses per kg body weight and proportion of patients
      with once/twice daily insulin injection were taken from the above mentioned RCT.
      Unit costs were taken from official German price lists and sources. Deterministic
      (DTA) and probabilistic sensitivity analyses (PSA) on resource use and unit costs
      were performed to test robustness of the results. RESULTS: Average annual
      treatment costs per patient (base case) were euro 849 for glargine and euro 1,334
      for detemir resulting in cost savings of euro 486 per patient per year (36%).
      Costs of insulins were euro 469 (IG) and euro 746 (ID). Costs of consumable items
      amounted at euro 380 (IG) and euro 588 (ID) respectively. Sensitivity analyses
      confirmed the findings in favor of insulin glargine. PSA results found cost
      savings ranging from euro 429 to euro 608 (5th/95th percentiles). CONCLUSIONS:
      The current model estimated that insulin glargine was associated with lower
      annual treatment costs of euro 486 (36%) compared to the use of insulin detemir
      while the same glycemic control is expected to be achieved.

PMID- 20137766
TI  - Pharmacokinetic comparisons of three nasal fentanyl formulations; pectin,
      chitosan and chitosan-poloxamer 188.
AB  - OBJECTIVES: To optimize the absorption profile and reduce C(max), three new
      fentanyl nasal spray formulations have been developed: fentanyl pectin (FPNS),
      fentanyl chitosan (FChNS) and fentanyl in chitosan-poloxamer 188 (FChPNS). The
      venous pharmacokinetic profiles and tolerability of these formulations were
      assessed and compared with oral transmucosal fentanyl citrate (OTFC) lozenge.
      SUBJECTS AND METHODS: This randomized, open-label, crossover study was conducted
      in opioid-naive, healthy adult volunteers. Subjects were dosed under naltrexone
      blockade on four occasions with three nasal sprays (100 microg in 100 microl) and
      OTFC 200 microg. Fentanyl venous plasma concentrations were measured up to 24 h
      post-dose. Tolerability was assessed by clinical nasal assessments and a nasal
      reactogenicity questionnaire. RESULTS: 18 subjects were enrolled and completed
      the study. The mean dose-normalized AUC(0-infinity) for each nasal formulation
      was significantly higher (p < 0.05) compared with OTFC. Bioavailability compared
      with OTFC was significantly greater for all nasal fentanyl formulations (FPNS
      132.4%, FChNS 154.1%, FChPNS 122.3%). Median tmax (FPNS 0.33 h, FChNS 0.17 h,
      FChPNS 0.26 h) were significantly (p < 0.001) reduced (OTFC 1.5 h) and mean
      C(max) significantly increased with all nasal formulations compared with OTFC.
      Nasal reactogenicity symptom incidence was lowest for the FPNS formulation (FPNS
      2, FChNS 28 and FChPNS 45). CONCLUSIONS: All nasal formulations demonstrated
      significantly increased systemic exposure and reduced times to peak plasma values
      compared with OTFC. The FPNS formulation exhibited the most favorable nasal and
      general tolerability profiles. It appears suitable for further investigation in
      breakthrough cancer pain management.

PMID- 20137767
TI  - Comparative bioavailability of two once-daily tramadol HCl 200 mg extended
      release products in healthy volunteers.
AB  - An open-label, randomized, 2-way crossover study was conducted to compare the
      pharmacokinetics of Tramadol Contramid OAD 200 mg tablets and Monocrixo L.P. 200
      mg capsules following single-dose administration under fasting conditions in 30
      healthy adult volunteers. Serial blood samples were collected at predefined time
      points over 48 hours post-dose and racemic tramadol and O-desmethyltramadol
      concentrations in plasma were determined using a validated LC-MS/MS method.
      Pharmacokinetic parameters were derived using noncompartmental methods. Results
      were compared using an analysis of variance (ANOVA) and the bioequivalence
      determination was based on the 90% confidence intervals for C(max), AUC(0-t) and
      AUC(0-infinity). Although the two products were determined to be bioequivalent
      with respect to C(max) and AUC, the time to reach peak tramadol concentrations
      was significantly earlier for Tramadol Contramid OAD (6 hours vs. 10 hours). A
      mean tramadol concentration of 100 ng/ml was attained within 1 hour for Tramadol
      Contramid OAD compared with > 4 hours for Monocrixo L.P. Both products were well
      tolerated.

PMID- 20137768
TI  - Differences in bioavailability between 60 mg of nifedipine osmotic push-pull
      systems after fasted and fed administration.
AB  - OBJECTIVES: This study was designed to evaluate and compare the bioavailability
      of two osmotically active formulations of 60 mg nifedipine, Gen-Nifedipine
      extended release Test tablets (Genpharm ULC, Etobicoke, ON, Canada) and Adalat XL
      Reference tablets (Bayer Healthcare AG, Leverkusen, Germany) after single dose
      fasted and fed administration. MATERIALS AND METHODS: The study was performed
      following a 4-period crossover design with both investigational products obtained
      from marketed batches. The complete pharmacokinetic evaluation was carried out in
      26 healthy male subjects with a median age of 29.5 years (range 18 - 44 years),
      mean weight of 79.7 kg (range 66.0 - 97.5 kg), and a mean body mass index (BMI)
      of 24.1 kg/m(2) (range 22.1 - 26.9 kg/m(2)). Tablets were administered with tap
      water either under fasting conditions or immediately following a high-fat, high
      calorie breakfast. Blood samples were taken predose and at pre-defined time
      points until 48 h post dosing. Samples were protected from light during handling
      and frozen until analysis. A validated LC-MS/MS method was used for the
      quantification of nifedipine in plasma samples. All kinetic parameters were
      determined model-independently for each treatment directly from measured
      concentrations. Monitoring of subject safety was accomplished by routine
      monitoring of blood pressure, heart rate and probing for adverse events. RESULTS:
      In-vitro dissolution curves show later onset and considerably lower quantity of
      nifedipine release from Test compared to Reference tablets. Under fasting
      conditions total and maximum exposure, represented by geometric mean AUC(0-tlast)
      and C(max)-values, respectively were 466.7 h*ng/ml (AUC(0-tlast)) and 21.9 ng/ml
      (C(max)) for Test and 507.8 h*ng/ml (AUC(0-tlast)) and 22.0 ng/ml (C(max)) for
      Reference tablets. However, the Test product exhibited a notably longer lag-time
      and less rapid onset of absorption than the Reference tablets. Moreover, the
      plateau phase is maintained for about 14 hours on Test but for almost 20 hours on
      Reference. Point estimates (PE) and associated 90% confidence intervals (CI) were
      determined as 91.8% and 79.9 - 105.5% for AUC(0-tlast), as well as 99.8% and 88.6
      - 112.4% for C(max). Larger differences were found for AUC(0-9h) (PE: 54.8%; CI:
      45.8 - 65.5%) determined as parameter for early exposure. Under fed conditions,
      although the mean plasma concentration time curves look similar in shape,
      concentrations of Test compared to Reference tablets are considerably lower at
      all time points until 36 hours after dosing. Again the lag time in onset of drug
      absorption is notably longer for the Test product. Both, total and maximum
      exposure, represented by geometric mean values for AUC(0-tlast) and C(max), were
      considerably lower (differences also statistically significant) after
      administration of Test with 481.8 h*ng/ml for AUC(0-tlast) and 25.3 ng/ml for
      C(max) in comparison to Reference tablets with 595.9 h*ng/ml for AUC(0-tlast) and
      31.9 ng/ml for C(max). Test/Reference point estimates (PE) and associated 90%
      confidence intervals (CI) were determined as 80.7% and 73.7 - 88.5% for AUC(0
      tlast), as well as 79.6% and 70.3 - 90.0% for C(max). Differences were also even
      more expressed for AUC(0-9h) (PE: 54.9%; CI: 47.4 - 63.5%) determined as
      parameter for early exposure. CONCLUSION: The results indicate that although both
      products are osmotic release systems they are not bioequivalent according to the
      accepted standards. This difference between both osmotic delivery systems might
      be substantiated by the fact that the core of the Test product is designed as a
      monolayer system (containing both, the active ingredient and the osmotic
      component) while Reference tablets consist of two separate layers. The observed
      pharmacokinetic differences may have an impact on blood pressure control in
      patients and thus, should be kept in mind when switching during treatment.

PMID- 20137769
TI  - Is 1-methylxanthine an ideal model substrate for establishing the renal tubular
      transport of organic ions?

PMID- 20137770
TI  - [Nasal packing in posterior epistaxis. Comparison of two methods].
AB  - OBJECTIVE: To evaluate tolerance and efficiency of two nasal blocking systems for
      posterior refractory epistaxis. PATIENTS AND METHODS: A five year comparative and
      longitudinal prospective study was developed in patients with epistaxis who
      attended our Emergency Unit and who required posterior nasal packing. Two groups
      were considered: one group was treated with a bi-chamber pneumatic inflation
      system (n=105). In other one, posterior occlusion was carried out with gauze,
      accessing through the mouth and using nasal reinforcement (n=47). The tolerance
      was measured by means of an analogue scale of pain intensity during the placement
      and maintenance of the packing, as well as for the need of analgesia. The
      efficiency was evaluated by episodes of re-bleeding, need for other concomitant
      measures, blood transfusion and side effects. RESULTS: In patients with
      inflatable nasal packing its placement was significantly faster (36+/-19s vs.
      228+/-102 s; p<0.001) and less painful (6.7+/-1.7 vs. 8.3+/-1.5; p<0.001),
      requiring less analgesia until its removal. Patients with pack of gauze showed a
      lower average incidence of re-bleeding (17% vs. 26 %; p<0.001), fewer cases of
      blood transfusion (15% vs. 18%; p<0.001) or of other procedures (4% vs. 11 %;
      p<0.001). The sanitary cost of the latter was also lower (1327+/-202 euro vs.
      1648+/-318 euro; p<0.001) and it generated less short and long-term complications
      CONCLUSIONS: The classical posterior packing with gauze is less rapid and
      comfortable to adapt, but it ensures a higher success rate in the control of
      epistaxis, produces fewer local injuries and reduces sanitary costs in comparison
      with inflatable balloon packing.

PMID- 20137771
TI  - How many response options? A study of remember-know testing procedures.
AB  - The remember-know procedure can be conducted in one or two steps. The one-step
      procedure does not include a recognition response (old-new) prior to the remember
      know response. It is observed consistently that the one-step procedure leads to a
      more liberal placement of the response criterion, but it is unclear whether
      recognition accuracy is affected by the number of procedural steps. However,
      previous studies used bias-dependent measures of accuracy (A' and d'). We
      manipulated the number of steps and confirmed the finding that the response
      criterion is more liberal with the one-step procedure. More importantly, we
      employed a signal detection theory bias-free accuracy measure (d(a)) to show that
      varying the number of steps does not affect recognition accuracy, and we
      demonstrated that this pattern of results does not change when the dual process
      signal detection model (Yonelinas, 1997) is applied.

PMID- 20137772
TI  - Autosomal-recessive hypophosphatemic rickets is associated with an inactivation
      mutation in the ENPP1 gene.
AB  - Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been
      shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked
      recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We
      present the identification of an inactivating mutation in the ecto-nucleotide
      pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive
      hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1
      generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of
      calcification, and previously described inactivating mutations in this gene were
      shown to cause aberrant ectopic calcification disorders, whereas no aberrant
      calcifications were present in our patients. Our surprising result suggests a
      different pathway involved in the generation of ARHR and possible additional
      functions for ENPP1.

PMID- 20137773
TI  - Loss-of-function ENPP1 mutations cause both generalized arterial calcification of
      infancy and autosomal-recessive hypophosphatemic rickets.
AB  - The analysis of rare genetic disorders affecting phosphate homeostasis led to the
      identification of several proteins that are essential for the renal regulation of
      phosphate homeostasis; for example, fibroblast growth factor 23 (FGF23), which
      inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis.
      Here, we report presumable loss-of-function mutations in the ENPP1 gene
      (ectonucleotide pyrophosphatase/phosphodiesterase) in members of four families
      affected with hypophosphatemic rickets. We provide evidence for the conclusion
      that ENPP1 is the fourth gene-in addition to PHEX, FGF23, and DMP1-that, if
      mutated, causes hypophosphatemic rickets resulting from elevated FGF23 levels.
      Surprisingly, ENPP1 loss-of-function mutations have previously been described in
      generalized arterial calcification of infancy, suggesting an as yet elusive
      mechanism that balances arterial calcification with bone mineralization.

PMID- 20137774
TI  - Mutations in Grxcr1 are the basis for inner ear dysfunction in the pirouette
      mouse.
AB  - Recessive mutations at the mouse pirouette (pi) locus result in hearing loss and
      vestibular dysfunction due to neuroepithelial defects in the inner ear. Using a
      positional cloning strategy, we have identified mutations in the gene Grxcr1
      (glutaredoxin cysteine-rich 1) in five independent allelic strains of pirouette
      mice. We also provide sequence data of GRXCR1 from humans with profound hearing
      loss suggesting that pirouette is a model for studying the mechanism of
      nonsyndromic deafness DFNB25. Grxcr1 encodes a 290 amino acid protein that
      contains a region of similarity to glutaredoxin proteins and a cysteine-rich
      region at its C terminus. Grxcr1 is expressed in sensory epithelia of the inner
      ear, and its encoded protein is localized along the length of stereocilia, the
      actin-filament-rich mechanosensory structures at the apical surface of auditory
      and vestibular hair cells. The precise architecture of hair cell stereocilia is
      essential for normal hearing. Loss of function of Grxcr1 in homozygous pirouette
      mice results in abnormally thin and slightly shortened stereocilia. When
      overexpressed in transfected cells, GRXCR1 localizes along the length of actin
      filament-rich structures at the dorsal-apical surface and induces structures with
      greater actin filament content and/or increased lengths in a subset of cells. Our
      results suggest that deafness in pirouette mutants is associated with loss of
      GRXCR1 function in modulating actin cytoskeletal architecture in the developing
      stereocilia of sensory hair cells.

PMID- 20137775
TI  - Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family
      with rhabdoid tumor predisposition syndrome.
AB  - Rhabdoid tumors of early infancy are highly aggressive with consequent poor
      prognosis. Most cases show inactivation of the SMARCB1 (also known as INI1 and
      hSNF5) tumor suppressor, a core member of the ATP-dependent SWI/SNF chromatin
      remodeling complex. Familial cases, described as rhabdoid tumor predisposition
      syndrome (RTPS), have been linked to heterozygous SMARCB1 germline mutations. We
      identified inactivation of another member of the SWI/SNF chromatin-remodeling
      complex, its ATPase subunit SMARCA4 (also known as BRG1), due to a SMARCA4/BRG1
      germline mutation and loss of heterozygosity by uniparental disomy in the tumor
      cells of two sisters with rhabdoid tumors lacking SMARCB1 mutations. SMARCA4 is
      thus a second member of the SWI/SNF complex involved in cancer predisposition.
      Its general involvement in other tumor entities remains to be established.

PMID- 20137776
TI  - Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD
      helicase family member DDX11/ChlR1.
AB  - The iron-sulfur-containing DNA helicases XPD, FANCJ, DDX11, and RTEL represent a
      small subclass of superfamily 2 helicases. XPD and FANCJ have been connected to
      the genetic instability syndromes xeroderma pigmentosum and Fanconi anemia. Here,
      we report a human individual with biallelic mutations in DDX11. Defective DDX11
      is associated with a unique cellular phenotype in which features of Fanconi
      anemia (drug-induced chromosomal breakage) and Roberts syndrome (sister chromatid
      cohesion defects) coexist. The DDX11-deficient patient represents another
      cohesinopathy, besides Cornelia de Lange syndrome and Roberts syndrome, and shows
      that DDX11 functions at the interface between DNA repair and sister chromatid
      cohesion.

PMID- 20137777
TI  - Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal
      dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome.
AB  - Frank-Ter Haar syndrome (FTHS), also known as Ter Haar syndrome, is an autosomal
      recessive disorder characterized by skeletal, cardiovascular, and eye
      abnormalities, such as increased intraocular pressure, prominent eyes, and
      hypertelorism. We have conducted homozygosity mapping on patients representing 12
      FTHS families. A locus on chromosome 5q35.1 was identified for which patients
      from nine families shared homozygosity. For one family, a homozygous deletion
      mapped exactly to the smallest region of overlapping homozygosity, which contains
      a single gene, SH3PXD2B. This gene encodes the TKS4 protein, a phox homology (PX)
      and Src homology 3 (SH3) domain-containing adaptor protein and Src substrate.
      This protein was recently shown to be involved in the formation of actin-rich
      membrane protrusions called podosomes or invadopodia, which coordinate
      pericellular proteolysis with cell migration. Mice lacking Tks4 also showed
      pronounced skeletal, eye, and cardiac abnormalities and phenocopied the majority
      of the defects associated with FTHS. These findings establish a role for TKS4 in
      FTHS and embryonic development. Mutation analysis revealed five different
      homozygous mutations in SH3PXD2B in seven FTHS families. No SH3PXD2B mutations
      were detected in six other FTHS families, demonstrating the genetic heterogeneity
      of this condition. Interestingly however, dermal fibroblasts from one of the
      individuals without an SH3PXD2B mutation nevertheless expressed lower levels of
      the TKS4 protein, suggesting a common mechanism underlying disease causation.

PMID- 20137778
TI  - Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal
      recessive nonsyndromic hearing impairment.
AB  - We identified overlapping homozygous regions within the DFNB25 locus in two Dutch
      and ten Pakistani families with sensorineural autosomal-recessive nonsyndromic
      hearing impairment (arNSHI). Only one of the families, W98-053, was not
      consanguineous, and its sibship pointed toward a reduced critical region of 0.9
      Mb. This region contained the GRXCR1 gene, and the orthologous mouse gene was
      described to be mutated in the pirouette (pi) mutant with resulting hearing loss
      and circling behavior. Sequence analysis of the GRXCR1 gene in hearing-impaired
      family members revealed splice-site mutations in two Dutch families and a
      missense and nonsense mutation, respectively, in two Pakistani families. The
      splice-site mutations are predicted to cause frameshifts and premature stop
      codons. In family W98-053, this could be confirmed by cDNA analysis. GRXCR1 is
      predicted to contain a GRX-like domain. GRX domains are involved in reversible S
      glutathionylation of proteins and thereby in the modulation of activity and/or
      localization of these proteins. The missense mutation is located in this domain,
      whereas the nonsense and splice-site mutations may result in complete or partial
      absence of the GRX-like domain or of the complete protein. Hearing loss in
      patients with GRXCR1 mutations is congenital and is moderate to profound.
      Progression of the hearing loss was observed in family W98-053. Vestibular
      dysfunction was observed in some but not all affected individuals. Quantitative
      analysis of GRXCR1 transcripts in fetal and adult human tissues revealed a
      preferential expression of the gene in fetal cochlea, which may explain the
      nonsyndromic nature of the hearing impairment.

PMID- 20137779
TI  - A missense mutation in the aggrecan C-type lectin domain disrupts extracellular
      matrix interactions and causes dominant familial osteochondritis dissecans.
AB  - Osteochondritis dissecans is a disorder in which fragments of articular cartilage
      and subchondral bone dislodge from the joint surface. We analyzed a five
      generation family in which affected members had autosomal-dominant familial
      osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan
      (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN
      revealed heterozygosity for a missense mutation (c.6907G > A) in affected
      individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3
      domain C-type lectin, which mediates interactions with other proteins in the
      cartilage extracellular matrix. Binding studies with recombinant mutated and wild
      type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions
      for the V2303M protein. Mass spectrometric analyses of aggrecan purified from
      patient cartilage verified that V2303M aggrecan is produced and present in the
      tissue. Our results provide a molecular mechanism for the etiology of familial
      osteochondritis dissecans and show the importance of the aggrecan C-type lectin
      interactions for cartilage function in vivo.

PMID- 20137781
TI  - [Mullerian inhibitor substance: from gene to protein, its role in clinical
      practice].
AB  - Mullerian inhibiting substance (MIS) has been discovered by Alfred Jost at the
      beginning of the fifties. MIS is a glycoprotein belonging to the TGF-beta family.
      Its various functions differ between males and females and according to the age
      of the individual. In male, the protein is synthesized by Sertoli's cells and
      induces the disappearance of Mullerian's ducts, the development of the male
      genital tract. Its role in adult males remains quite unknown. In female, the
      protein is secreted by granulosa cells and plays a role during folliculogenesis
      as it regulates the initial and cyclic recruitment of ovarian follicles. MIS is
      also a good marker of follicular reserve and ovarian function. Therefore, it
      plays a role in different areas such as assisted medical reproduction and
      oncology. This protein represents a potential major diagnosis as well as
      prognostic tool in reproduction.

PMID- 20137780
TI  - ROADTRIPS: case-control association testing with partially or completely unknown
      population and pedigree structure.
AB  - Genome-wide association studies are routinely conducted to identify genetic
      variants that influence complex disorders. It is well known that failure to
      properly account for population or pedigree structure can lead to spurious
      association as well as reduced power. We propose a method, ROADTRIPS, for case
      control association testing in samples with partially or completely unknown
      population and pedigree structure. ROADTRIPS uses a covariance matrix estimated
      from genome-screen data to correct for unknown population and pedigree structure
      while maintaining high power by taking advantage of known pedigree information
      when it is available. ROADTRIPS can incorporate data on arbitrary combinations of
      related and unrelated individuals and is computationally feasible for the
      analysis of genetic studies with millions of markers. In simulations with related
      individuals and population structure, including admixture, we demonstrate that
      ROADTRIPS provides a substantial improvement over existing methods in terms of
      power and type 1 error. The ROADTRIPS method can be used across a variety of
      study designs, ranging from studies that have a combination of unrelated
      individuals and small pedigrees to studies of isolated founder populations with
      partially known or completely unknown pedigrees. We apply the method to analyze
      two data sets: a study of rheumatoid arthritis in small UK pedigrees, from
      Genetic Analysis Workshop 15, and data from the Collaborative Study of the
      Genetics of Alcoholism on alcohol dependence in a sample of moderate-size
      pedigrees of European descent, from Genetic Analysis Workshop 14. We detect
      genome-wide significant association, after Bonferroni correction, in both
      studies.

PMID- 20137782
TI  - [Choroidal and scalp metastasis in breast cancer].

PMID- 20137783
TI  - [Current indications, surgical technique and results of anterior sphincter repair
      as a treatment of faecal incontinence].
AB  - Faecal incontinence is a high prevalence disease in the general population. This
      pathology is commonly under-estimated and causes a great impact on clinical
      status and on the quality of life of affected patients. The prevalence of faecal
      incontinence in several studies has been estimated between 2% and 15% of the
      general population. The prevalence increases if we study selected populations,
      such as elderly people. The main cause of faecal incontinence is obstetric anal
      sphincter damage. In the past years, the presence of incontinence due to
      sphincter lesions, especially the obstetric ones, was an absolute indication of
      anterior anal sphincter repair. Actually, after knowing the long term follow up
      results of this technique, as well as the evolving knowledge on faecal
      incontinence and the development of new diagnostic and therapeutic techniques,
      this technique might be selected for cases with large sphincter defects. However
      there is limited information in the current literature on indications, surgical
      technique and results of anterior sphincter repair. The aim of this review is to
      analyse scientific evidence on current indications, surgical technique features
      and results of anterior sphincter repair as a therapy for faecal incontinence,
      also giving our point of view on controversial issues. A bibliography search was
      undertaken using Medline database including articles published from January 1985
      to January 2009.

PMID- 20137784
TI  - Please add the journal issue number to Cortex references.

PMID- 20137785
TI  - Blastocyst versus cleavage stage transfer in in vitro fertilization: differences
      in neonatal outcome?
AB  - OBJECTIVE: To compare neonatal outcome of blastocyst and cleavage stage embryo
      transfers after IVF. DESIGN: Register study. SETTING: Births recorded in the
      Swedish Medical Birth Register after IVF performed, 2002-2006. PATIENT(S):
      Treatments reported from all Swedish IVF clinics. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Some neonatal characteristics were compared in 1,311 infants
      born after blastocyst-stage transfer and 12,562 infants born after cleavage-stage
      transfer. Comparisons were also made with all births, 2002-2007 (n = 598,687).
      RESULT(S): After adjusting for year of birth, maternal age, parity, smoking
      habits, and body mass index, the risk of preterm birth among singletons was
      significantly greater after blastocyst-stage transfer than after cleavage-stage
      transfer. The risk of congenital malformations was also significantly higher.
      When the analysis was restricted to clinics where blastocyst transfers were made,
      the risk estimates increased for preterm birth, low birth weight, low APGAR
      score, and respiratory diagnoses, but did not change for congenital
      malformations. CONCLUSION(S): The results indicate a small increase in risk
      associated with blastocyst transfer, perhaps owing to the longer period of in
      vitro culture. There is a possibility that this effect is due, at least in part,
      to a selection of women for blastocyst transfers. Further studies are needed
      either to verify or to refute the found associations.

PMID- 20137786
TI  - The efficacy of multiple-dose methotrexate treatment for unruptured tubal ectopic
      pregnancy and conversion rate to surgery: a study on 294 cases.
AB  - In this prospective study 294 patients diagnosed with ectopic pregnancy (EP) were
      treated with multiple-dose methotrexate (MTX) to determine the conversion rate to
      surgery. We concluded that multiple-dose MTX treatment had a low success rate,
      and the success rate was not related to initial b-hCG value; it was more related
      to the size of gestational mass before treatment.

PMID- 20137787
TI  - Inhibition of cell proliferation, adhesion, and invasion with an anti-L1-cell
      adhesion molecule monoclonal antibody in an in vitro endometriosis model.
AB  - The use of anti-L1-cell adhesion molecule monoclonal antibodies (anti-L1CAM-mAb)
      in an endometriosis epithelial cell line Z12 led to a statistically significant
      decrease in cell proliferation and cell invasion and to an inhibition of the
      adhesion compared with unspecific IgG-Ab treated and untreated cells. Because it
      increases the cell invasion and adhesion which consequently aggravates the
      disease, L1 could possibly promote endometriosis development; thus, further
      studies should evaluate the possible use of anti-L1-mAb in an animal
      endometriosis model.

PMID- 20137788
TI  - A simple technique for reducing posterior hip dislocation: The foot-fulcrum
      manoeuvre.

PMID- 20137789
TI  - Decreased endothelin-1 levels after acute consumption of red wine and de
      alcoholized red wine.
AB  - BACKGROUND: Red wine consumption may influence on vasoconstrictive peptide
      endothelin-1 levels, and this may be one mechanism leading to improved
      vasodilation after red wine consumption. Endothelin-1 levels and their
      association with coronary epicardial diameter and flow rate, however, have not
      been studied in vivo after consumption of red wine and de-alcoholized red wine.
      The purpose of this randomized trial was to determine the acute effects of these
      beverages on endothelin-1 levels and compare them to coronary artery epicardial
      diameter and flow rate. METHODS: Twenty-two healthy men consumed a high dose
      (8.1+/-0.9 dL) of alcohol-containing red wine and de-alcoholized red wine in a
      cross-over design at one sitting with a two-week washout period. Endothelin-1
      levels were determined and coronary artery diameter and flow rate assessed using
      transthoracic echocardiography before and acutely after intervention. RESULTS:
      Red wine and de-alcoholized red wine significantly decreased endothelin-1 levels
      (0.75+/-0.26 pg/mL to 0.61+/-0.20 pg/mL, p=0.002; 0.74+/-0.32 pg/mL to 0.63+/
      0.24 pg/mL, p=0.04, respectively), but did not have a significant effect on
      epicardial diameter (1.1+/-0.3 mm vs. 1.1+/-0.3 mm, p=0.58; and 1.1+/-0.3 mm vs.
      1.1+/-0.2 mm, p=0.10, respectively) or flow rate (7.8+/-4.0 mL/min to 6.4+/-3.6
      mL/min, p=0.07; and 7.8+/-4.0 mL/min to 7.4+/-3.2 mL/min, p=0.53, respectively).
      CONCLUSIONS: Red wine and de-alcoholized red wine decreased plasma endothelin-1
      levels after acute consumption, but this change was not reflected in coronary
      epicardial diameters or flow rate.

PMID- 20137790
TI  - Surface diffusion in reversed-phase liquid chromatography.
AB  - More than 40 years ago, Giddings pointed out in "Dynamics of Chromatography" that
      surface diffusion should become an important research topic in the kinetics of
      chromatographic phenomena. However, few studies on surface diffusion in
      adsorbents used in chromatography were published since then. Most scientists use
      ordinary rate equations to study mass transfer kinetics in chromatography. They
      take no account of surface diffusion and overlook the significant contributions
      of this mass transfer process to chromatographic behavior and to column
      efficiency at high mobile phase flow rate. Only recently did the significance of
      surface diffusion in separation processes begin to be recognized in connection
      with the development of new techniques of fast flow, high efficiency
      chromatography. In this review, we revisit the reports on experimental data on
      surface diffusion and introduce a surface-restricted molecular diffusion model,
      derived as a first approximation for the mechanism of surface diffusion, on the
      basis of the absolute rate theory. We also explain how this model accounts for
      many intrinsic characteristics of surface diffusion that cannot properly be
      explained by the conventional models of surface diffusion.

PMID- 20137791
TI  - Mass fragmentation study of the trimethylsilyl derivatives of arctiin,
      matairesinoside, arctigenin, phylligenin, matairesinol, pinoresinol and
      methylarctigenin: their gas and liquid chromatographic analysis in plant
      extracts.
AB  - The mass fragmentation patterns and the characteristic behavior of the
      trimethylsilyl (TMS) derivatives of the dibenzylbutyrolactone-type (arctiin,
      arctigenin, methylarctigenin, matairesinoside, matairesinol) and those of the
      diphenylperhydrofurotetrahydrofurane-type (phylligenin, pinoresinol) lignans,
      obtained by gas chromatography-mass spectrometry (GC-MS), were presented. It was
      shown that upon acidic hydrolysis the dibenzylbutyrolactone-type lignans are
      stable while the diphenylperhydrofurotetrahydrofurane-type ones decompose. As a
      novelty to the field we confirmed that the fragment species of the derivatized
      lignan glycosides, in the presence of excess hexamethyldisilazane, leaded to
      their in situ derivatization. Quantification of the selective fragment ions of
      the TMS derivatives by GC-MS, in respect of the ions found one by one, and
      concerning the selective fragment ions {SFI(s)} in total, provided acceptable
      reproducibilities, suitable for quantitation purposes: varying between 1.20% and
      6.6% relative standard deviation percentages (RSD%). For characterization of the
      behavior of various type of lignans, analyses were performed with the untreated
      and with the trifluoroacetic acid hydrolyzed plant extracts, from the same
      sample, in parallel, both by GC-MS and by high performance liquid chromatography
      mass spectrometry, working in the positive electron ionization mode (HPLC-ESPI
      MS). The analysis of lignans in fruit and leaf extracts (obtained from the
      Arctium, Centaurea and Forsythia plants) was confirmed both by GC-MS and by HPLC
      ESPI-MS. Our multicomponent system (including the identification and
      quantification of sugars, sugar alcohols, and several members of various
      homologous series of acids, anthraquinones and flavonoids) has been extended to
      the analysis of lignan glycosides and to the free lignans. Reproducibilities in
      the quantitation of lignans in plant matrices, as averages on GC and HPLC basis,
      varied between 0.9% and 11% (RSD). The distribution of the lignan constituents
      was presented for 5 Arctium, for 8 Centaurea and for 4 Forsythia plant extracts:
      the total of lignan contents varied between 0.42 and 87.9 mg/g, respectively.

PMID- 20137792
TI  - [Are we really so good treating diabetes?].

PMID- 20137793
TI  - [Retinopathy and renal failure in a patient with multiple sclerosis under
      treatment with beta-interferon].

PMID- 20137795
TI  - Constituents and secondary metabolite natural products in fresh and deteriorated
      cassava roots.
AB  - A phytochemical analysis of cassava (Manihot esculenta Crantz) fresh roots and
      roots suffering from post-harvest physiological deterioration (PPD) has been
      carried out. The first isolation and identification of galactosyl
      diacylglycerides from fresh cassava roots is reported, as well as beta-carotene,
      linamarin, and beta-sitosterol glucopyranoside. The hydroxycoumarin scopoletin
      and its glucoside scopolin were identified from cassava roots during PPD, as well
      as trace quantities of esculetin and its glucoside esculin. There is no
      isoscopoletin in cassava roots during PPD.

PMID- 20137796
TI  - Fluconazole decreases cyclosporine dosage in renal transplanted dogs.
AB  - The effect of fluconazole (Fcz) on the cyclosporine (CsA) dosage was investigated
      in renal transplanted dogs receiving CsA-based immunosuppressive therapy.
      Initially, CsA was administered orally twice daily to raise the blood trough
      level between 400 and 600 ng/ml. After the addition of Fcz, the CsA dosage was
      adjusted to maintain its therapeutic blood concentration. Fcz significantly
      decreased CsA dosage in both normal and renal transplanted dogs, but a higher
      dosage of CsA was needed in renal transplanted dogs. In conclusion, Fcz decreases
      required CsA dosage and thereby reduces the cost of immunosuppressive therapy in
      canine renal transplantation.

PMID- 20137797
TI  - Detection and genotyping of porcine circovirus in naturally infected pigs by
      oligo-microarray.
AB  - A rapid and reliable method for the identification of porcine circovirus (PCV)
      genotypes based on oligonucleotide microarray hybridization has been developed.
      The genotype-specific oligonucleotides (22-30 mer) immobilized on the surface of
      glass slides were selected to bind to the multiple target sites within the
      replication gene that are conserved among individual PCV genotypes. Cy5-labeled
      DNA targets were amplified in a PCR with primers common to both genotypes. The
      identification of PCV genotype was based on hybridization with several individual
      genotype-specific oligonucleotides. This approach combines the high sensitivity
      of PCR with the selectivity of DNA-DNA hybridization. The utility and feasibility
      of oligonucleotide microarray hybridization was evaluated by testing standard and
      87 clinical isolates. Analysis of the specimens showed that this microarray-based
      method is capable of unambiguous identification of both genotypes and fivefold
      more sensitive than gel electrophoresis. Our results indicated that the
      oligonucleotide array is useful for the identification and discrimination of PCV
      from clinical isolates and specimens in a clinical laboratory.

PMID- 20137798
TI  - Expression of drug efflux transporters in poultry tissues.
AB  - Multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 2
      (MRP2) are two prominent members of the super-family of ATP-binding cassette
      (ABC) transporters that carry a wide range of substrates across biological
      membranes, using ATP as energy source. The level of expression of these efflux
      transporters in different tissues has hitherto been studied mainly in mammals,
      and only P-glycoprotein (P-gp), the product of the MDR1 gene, has been described
      in chickens as of yet. The aim of this study was to describe the levels of
      expression of MDR1 and MRP2 mRNAs in different tissues of chickens, as these
      transporters play an important role in the absorption, distribution and excretion
      of drugs and toxins. In the gastro-intestinal tract, the highest levels of MDR1
      mRNA expression were found in the small intestines, followed by the colon,
      whereas lower levels were found in the crop, proventriculus and the caeca. High
      MDR1 expression was also measured in the excretory organs such as liver, kidney
      and lungs. In contrast to rodents and humans, relatively low levels were found in
      the adrenals and in the immature sex organs such as testicles and ovaries. MRP2
      mRNA expression was high in the liver, kidneys, duodenum and the jejunum, but
      expression was low in the ileum as well as in the lungs. No MRP2 expression could
      be detected in the other organs tested. Comparing the findings in chickens with
      previously published data, in particular those from humans and rodents, an
      unexpected high degree of similarity in the expression pattern of MDR1 and MRP2
      mRNAs was apparent.

PMID- 20137799
TI  - Efficient, trans-complementing packaging systems for chimeric, pseudoinfectious
      dengue 2/yellow fever viruses.
AB  - In our previous studies, we have stated to build a new strategy for developing
      defective, pseudoinfectious flaviviruses (PIVs) and applying them as a new type
      of vaccine candidates. PIVs combined the efficiency of live vaccines with the
      safety of inactivated or subunit vaccines. The results of the present work
      demonstrate further development of chimeric PIVs encoding dengue virus 2 (DEN2V)
      glycoproteins and yellow fever virus (YFV)-derived replicative machinery as
      potential vaccine candidates. The newly designed PIVs have synergistically
      functioning mutations in the prM and NS2A proteins, which abolish processing of
      the latter proteins and make the defective viruses capable of producing either
      only noninfectious, immature and/or subviral DEN2V particles. The PIV genomes can
      be packaged to high titers into infectious virions in vitro using the NS1
      deficient YFV helper RNAs, and both PIVs and helpers can then be passaged as two
      component genome viruses at an escalating scale.

PMID- 20137800
TI  - Both homo and heterodimers of Marek's disease virus encoded Meq protein
      contribute to transformation of lymphocytes in chickens.
AB  - Marek' disease virus serotype-1, also know as Gallid herpesvirus 2 (GaHV-2),
      elicits T-cell lymphomas in chickens. The GaHV-2 genome encodes an oncoprotein,
      Meq, with similarity to the Jun/Fos family of proteins. We have previously shown
      that Meq homodimers are not sufficient to induce lymphomas in chickens. In this
      study, we investigated the role of Meq heterodimers in the pathogenicity of GaHV
      2 by generating a chimeric meq gene, which contains the leucine zipper region of
      Fos (meqFos). A recombinant virus containing the meqFos gene in place of parental
      meq, rMd5-MeqFos, was not capable of transforming chicken lymphocytes, indicating
      that heterodimerization of Meq alone is not sufficient for transformation. In
      addition, the recovery of the oncogenic phenotype by a recombinant virus encoding
      one copy each of MeqGCN (homodimer) and MeqFos (heterodimer) conclusively
      demonstrates that both homo and heterodimerization of Meq are required for
      oncogenesis.

PMID- 20137801
TI  - The role of Cajal bodies in the expression of late phase adenovirus proteins.
AB  - Cajal bodies (CBs) are subnuclear structures involved in RNA metabolism. Here we
      show that, following infection of HeLa cells by adenovirus type 5 (Ad5), CBs
      fragment and form ordered structures, which we have termed "rosettes". Formation
      of CB rosettes was prevented by inhibition of viral DNA synthesis and preceded
      expression of the L4-33K protein. CB rosettes localised to the periphery of E2A
      72K-containing replication centers and to the edges of ASF/SF2 and hnRNP A1 ring
      structures that demarcate sites of viral transcription and splicing. At later
      times of infection, CB rosettes were undetectable. Furthermore, knock-down of p80
      coilin (the major structural protein of CBs) by RNA interference reduced the
      yield of infectious Ad5 and expression of the late proteins IIIa (from L1), hexon
      (from L3) and fiber (from L5), whereas the E2A-72K protein was unaffected. We
      conclude that CBs have an important role in the expression of adenovirus major
      late gene products.

PMID- 20137803
TI  - SBBGR technology for minimising excess sludge production in biological processes.
AB  - This paper reports the results of an investigation aimed at evaluating the
      performance of an innovative technology (SBBGR system - Sequencing Batch
      Biofilter Granular Reactor), characterised by a low sludge production, for
      treating municipal wastewater at demonstrative scale. The results have shown that
      even at the maximum investigated organic load (i.e., 2.5 kg COD/m(3) d), the
      plant removed 80% of COD, total suspended solids and nitrogen content with
      relative residual concentrations lower than the Italian limits for discharge into
      soil. The process was characterised by a very low sludge production (i.e., 0.12
      0.14 kg TSS/kg COD(removed)) ascribable to the high sludge age in the system
      (thetac >120 d). Molecular in situ detection methods and microscopy staining
      procedures were employed in combination with the traditional measurements (oxygen
      uptake rate and total protein content) to evaluate both the microbial activity
      and composition, and the structure of the biomass. A stable presence of active
      bacterial populations (mainly Proteobacteria) was found within compact and dense
      aggregates.

PMID- 20137802
TI  - Visualization of feline calicivirus replication in real-time with recombinant
      viruses engineered to express fluorescent reporter proteins.
AB  - Caliciviruses are non-enveloped, icosahedral viruses with a single-stranded,
      positive sense RNA genome. Transposon-mediated insertional mutagenesis was used
      to insert a transprimer sequence into random sites of an infectious full-length
      cDNA clone of the feline calicivirus (FCV) genome. A site in the LC gene
      (encoding the capsid leader protein) of the FCV genome was identified that could
      tolerate foreign insertions, and two viable recombinant FCV variants expressing
      LC fused either to AcGFP, or DsRedFP were recovered. The effects of the
      insertions on LC processing, RNA replication, and stability of the viral genome
      were analyzed, and the progression of a calicivirus single infection and co
      infection were captured by real-time imaging fluorescent microscopy. The ability
      to engineer viable recombinant caliciviruses expressing foreign markers enables
      new approaches to investigate virus and host cell interactions, as well as
      studies of viral recombination, one of the driving forces of calicivirus
      evolution.

PMID- 20137804
TI  - Coexisting venous thromboembolism in patients with tuberculosis.

PMID- 20137805
TI  - Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a
      randomised controlled trial.
AB  - BACKGROUND: Surgical debridement was the standard treatment for Mycobacterium
      ulcerans infection (Buruli ulcer disease) until WHO issued provisional guidelines
      in 2004 recommending treatment with antimicrobial drugs (streptomycin and
      rifampicin) in addition to surgery. These recommendations were based on
      observational studies and a small pilot study with microbiological endpoints. We
      investigated the efficacy of two regimens of antimicrobial treatment in early
      stage M ulcerans infection. METHODS: In this parallel, open-label, randomised
      trial undertaken in two sites in Ghana, patients were eligible for enrolment if
      they were aged 5 years or older and had early (duration <6 months), limited
      (cross-sectional diameter <10 cm), M ulcerans infection confirmed by dry-reagent
      based PCR. Eligible patients were randomly assigned to receive intramuscular
      streptomycin (15 mg/kg once daily) and oral rifampicin (10 mg/kg once daily) for
      8 weeks (8-week streptomycin group; n=76) or streptomycin and rifampicin for 4
      weeks followed by rifampicin and clarithromycin (7.5 mg/kg once daily), both
      orally, for 4 weeks (4-week streptomycin plus 4-week clarithromycin group; n=75).
      Randomisation was done by computer-generated minimisation for study site and type
      of lesion (ulceration or no ulceration). The randomly assigned allocation was
      sent from a central site by cell-phone text message to the study coordinator. The
      primary endpoint was lesion healing at 1 year after the start of treatment
      without lesion recurrence or extensive surgical debridement. Analysis was by
      intention-to-treat. This trial is registered with ClinicalTrials.gov, number
      NCT00321178. FINDINGS: Four patients were lost to follow-up (8-week streptomycin,
      one; 4-week streptomycin plus 4-week clarithromycin, three). Since these four
      participants had healed lesions at their last assessment, they were included in
      the analysis for the primary endpoint. 73 (96%) participants in the 8-week
      streptomycin group and 68 (91%) in the 4-week streptomycin plus 4-week
      clarithromycin group had healed lesions at 1 year (odds ratio 2.49, 95% CI 0.66
      to infinity; p=0.16, one-sided Fisher's exact test). No participants had lesion
      recurrence at 1 year. Three participants had vestibulotoxic events (8-week
      streptomycin, one; 4-week streptomycin plus 4-week clarithromycin, two). One
      participant developed an injection abscess and two participants developed an
      abscess close to the initial lesion, which was incised and drained (all three
      participants were in the 4-week streptomycin plus 4-week clarithromycin group).
      INTERPRETATION: Antimycobacterial treatment for M ulcerans infection is effective
      in early, limited disease. 4 weeks of streptomycin and rifampicin followed by 4
      weeks of rifampicin and clarithromycin has similar efficacy to 8 weeks of
      streptomycin and rifampicin; however, the number of injections of streptomycin
      can be reduced by switching to oral clarithromycin after 4 weeks. FUNDING:
      European Union (EU FP6 2003-INCO-Dev2-015476) and Buruli Ulcer Groningen
      Foundation.

PMID- 20137806
TI  - Should antibiotics be given for Buruli ulcer?

PMID- 20137807
TI  - Retraction--Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and
      pervasive developmental disorder in children.

PMID- 20137808
TI  - Biodynamic modelling of the accumulation of Ag, Cd and Zn by the deposit-feeding
      polychaete Nereis diversicolor: inter-population variability and a generalised
      predictive model.
AB  - Biodynamic parameters of the ragworm Nereis diversicolor from southern Spain and
      south England were experimentally derived to assess the inter-population
      variability of physiological parameters of the bioaccumulation of Ag, Cd and Zn
      from water and sediment. Although there were some limited variations, these were
      not consistent with the local metal bioavailability nor with temperature changes.
      Incorporating the biodynamic parameters into a defined biodynamic model,
      confirmed that sediment is the predominant source of Cd and Zn accumulated by the
      worms, accounting in each case for 99% of the overall accumulated metals, whereas
      the contribution of dissolved Ag to the total accumulated by the worm increased
      from about 27 to about 53% with increasing dissolved Ag concentration.
      Standardised values of metal-specific parameters were chosen to generate a
      generalised model to be extended to N. diversicolor populations across a wide
      geographical range from western Europe to North Africa. According to the
      assumptions of this model, predicted steady state concentrations of Cd and Zn in
      N. diversicolor were overestimated, those of Ag underestimated, but still
      comparable to independent field measurements. We conclude that species-specific
      physiological metal bioaccumulation parameters are relatively constant over large
      geographical distances, and a single generalised biodynamic model does have
      potential to predict accumulated Ag, Cd and Zn concentrations in this polychaete
      from a single sediment metal concentration.

PMID- 20137809
TI  - Influence of tachykinin NK2 receptors on intestinal sensitivity and motility in
      newborn rats.
AB  - The effect of tachykinin neurokinin NK(2) receptors activation on intestinal
      propulsion and colorectal sensitivity was studied in 7-15 days old newborn rats.
      In a first set of experiments investigating the intestinal transit, the selective
      NK(2) receptor agonist, [betaAla(8)]NKA-(4-10) was used. It produced an increase
      of the small intestinal transit measured by charcoal test of 54%, that was
      inhibited in a dose-dependent manner by nepadutant ([N(4)-(2-acetamido-2-deoxy
      beta-D-glucopyranosyl)-L-asparaginyl-L-aspartyl-L-tryptophyl-L-phenylalanyl-L-2,3
      diaminopropionyl-L-leucyl]-C-4.2-N-3.5-lactam-C-1.6-N-2.1-lactam), a known
      selective NK(2) receptor antagonist, orally administered 2-48 h before the
      challenge with the NK(2) receptor agonist. Nepadutant did not affect the basal
      intestinal propulsion and showed a good oral bioavailability and long duration of
      action. In another set of experiments investigating visceral sensitivity, a fixed
      distension volume of a balloon inserted intrarectally in 14-15 days old newborns
      rats produced abdominal contractions (AC) that were increased after colonic
      application of acetic acid (50 microl, 0.5%). In this latter condition
      nepadutant, at 0.5 and 2.5 mg/kg p.o., significantly reduced the resulting AC. In
      control rats, untreated with acetic acid, nepadutant did not affect AC evoked by
      colorectal distension. These findings show for the first time two models to
      assess intestinal motility and visceral sensitivity in newborn rats and indicate
      nepadutant as a valuable tool to assess the role of NK(2) receptors in the
      intestinal propulsive and nociceptive activity in infants.

PMID- 20137810
TI  - A diphtheria toxin interleukin-3 fusion protein synergizes with tyrosine kinase
      inhibitors in killing leukemic progenitors from BCR/ABL positive acute leukemia.
AB  - Despite initial remissions, most patients with Ph chromosome positive (Ph(+))
      acute leukemia (AL) become refractory to tyrosine kinase inhibitors (TKIs) such
      as imatinib and dasatinib. This study was designed to determine if targeting the
      interleukin-3 receptor (IL-3R) with a diphtheria toxin fusion protein
      (DT(388)IL3) would improve the effectiveness of TKIs against Ph(+) AL cells. IL
      3R subunits were detected on most Ph(+) cells and the IC50 for killing of colony
      forming cell (CFC) with DT(388)IL3 correlated with the level of IL-3Ralpha
      subunit by FACS. DT(388)IL3 synergized with both imatinib and dasatinib for
      killing of malignant CFCs. Long-term suspension culture-initiating cells (SC-ICs)
      and quiescent leukemic cells (G(0) in cell cycle) also were studied and
      synergistic interactions were again demonstrated. Thus, cotreatment with TKIs and
      DT(388)IL3 is much more effective in eliminating Ph(+) leukemic progenitors that
      express IL-3R than either agent alone.

PMID- 20137811
TI  - Detangling fibrosis assessment in MPNs.

PMID- 20137812
TI  - Sub-lethal effects of cadmium on the antioxidant defence system of the
      hydrothermal vent mussel Bathymodiolus azoricus.
AB  - The mussel Bathymodiolus azoricus is one of the most abundant species in the Mid
      Atlantic Ridge hydrothermal vents and is continually exposed to the high
      temperature venting fluids containing high metal concentrations and enriched in
      sulphides and methane, which constitute a potential toxic environment for marine
      species. The aim of this study was to assess the effects of a sub-lethal Cd
      concentration on the antioxidant defence system of this mussel. B. azoricus were
      collected at Menez Gwen vent site (37 degrees 51'N, 32 degrees 31'W) and exposed
      to Cd (50 microg l(-1)) during 24 days, followed by a depuration period of six
      days. A battery of stress related biomarkers including antioxidant enzymes
      (superoxide dismutase-SOD, catalase-CAT; glutathione peroxidases-GPx),
      metallothioneins (MT), lipid peroxidation (LPO) and total oxyradical scavenging
      capacity (TOSC) were measured in the gills and mantle of B. azoricus. Cd was
      accumulated linearly during the exposure period in both tissues and no
      significant elimination occurred after the 6 days of depuration. Antioxidant
      enzymes activities were significantly higher in the gills. Cyt-SOD, T-GPx and Se
      GPx were induced during the experiment but this was also observed in control
      organisms. Mit-SOD and CAT activities remained relatively unchanged. MT levels
      increased linearly in the gills of exposed mussels in the first 18 days of
      exposure. No significant differences were observed between LPO levels of control
      and exposed mussels. TOSC levels remained unchanged in control and exposed
      mussels. This suggests that although Cd is being accumulated in the tissues of
      exposed mussels, MT defence system is enough to detoxify the effect of Cd
      accumulated in the tissues. Furthermore, other factors besides the presence of Cd
      are influencing the antioxidant defence system in B. azoricus.

PMID- 20137813
TI  - Neighbourhood planning improvement: physical attributes, cognitive and affective
      evaluation and activities in two neighbourhoods in Rome.
AB  - This study proposes a psychological analysis of the relationships between people
      and their residential environment in two neighbourhoods in Rome, within the
      theoretical framework of place theory. The analysis was aimed at getting
      indications for neighbourhood improvement, which can lead to residential
      satisfaction and neighbourhood attachment. We considered both constructs as the
      result of the relationships between the physical attributes of the environment,
      the cognitive perceptions and the affective appraisals of residents, and the
      activities they carry out. The role of socio-demographic and residential
      variables was also considered. Theoretical implications of results and
      indications for neighbourhood improvement are discussed. Residential satisfaction
      and neighbourhood attachment have a different pattern of predictors, emerging
      from all the dimensions of analysis we considered. Using hierarchical linear
      models, cognitive, affective and behavioural variables emerged as significant
      first-level predictors of both criteria, and physical attributes were found to be
      significant second-level predictors. In addition, the joint analysis of objective
      neighbourhood features and residents' experience within a place-specific
      framework showed to be an effective approach to identify relevant domains for
      neighbourhood improvement. Commercial and leisure facilities can contribute to
      make the neighbourhood more lively; building density and green areas have inverse
      effects on the prevalence of social activities.

PMID- 20137814
TI  - Preterm infant massage therapy research: a review.
AB  - In this paper, preterm infant massage therapy studies are reviewed. Massage
      therapy has led to weight gain in preterm infants when moderate pressure massage
      was provided. In studies on passive movement of the limbs, preterm infants also
      gained significantly more weight, and their bone density also increased. Research
      on ways of delivering the massage is also explored including using mothers versus
      therapists and the added effects of using oils. The use of mothers as therapists
      was effective in at least one study. The use of oils including coconut oil and
      safflower oil enhanced the average weight gain, and the transcutaneous absorption
      of oil also increased triglycerides. In addition, the use of synthetic oil
      increased vagal activity, which may indirectly contribute to weight gain. The
      weight gain was associated with shorter hospital stays and, thereby, significant
      hospital cost savings. Despite these benefits, preterm infant massage is only
      practiced in 38% of neonatal intensive care units. This may relate to the
      underlying mechanisms not being well understood. The increases noted in vagal
      activity, gastric motility, insulin and IGF-1 levels following moderate pressure
      massage are potential underlying mechanisms. However, those variables combined do
      not explain all of the variance in weight gain, highlighting the need for
      additional mechanism studies.

PMID- 20137815
TI  - The role of demonstrator familiarity and language cues on infant imitation from
      television.
AB  - An imitation procedure was used to investigate the impact of demonstrator
      familiarity and language cues on infant learning from television. Eighteen-month
      old infants watched two pre-recorded videos showing an adult demonstrating a
      sequence of actions with two sets of stimuli. Infants' familiarity with the
      demonstrator and the language used during the demonstration varied as a function
      of experimental condition. Immediately after watching each video, infants'
      ability to reproduce the target actions was assessed. A highly familiar
      demonstrator did not enhance infants' performance. However, the addition of a
      narrative, developed from mothers' naturalistic description of the event,
      facilitated learning from an unfamiliar demonstrator. We propose that the
      differential effect of demonstrator familiarity and language cues may reflect the
      infants' ability to distinguish between important and less important aspects in a
      learning situation.

PMID- 20137816
TI  - Maternal self-efficacy and hostile-reactive parenting from infancy to
      toddlerhood.
AB  - A longitudinal study of maternal self-efficacy (SE) and hostile-reactive
      parenting (HRP) was conducted with a community sample of 1836 mothers. Mothers
      completed questionnaires when their child was 4.5, 16.6 and 28.5 months of age.
      Maternal SE showed little change, whereas HRP sharply increased from 4.5 to 28.5
      months. Structural equation models suggest these initially correlated variables
      did not influence each other over time, but rather became increasingly
      independent. Three distinct developmental trajectories were fitted for both
      maternal SE and HRP. In contrast to the overall portrait of stability, 12.6% of
      mothers followed a trajectory of declining SE. Likewise, 12.1% of mothers showed
      initially high and sharply increasing HRP. Few mothers (3.1%) simultaneously
      followed both of these trajectories, yet overall, SE and HRP trajectories were
      modestly associated (tau(b)=-.23, p<.0001). Failure to support the expected
      reciprocal influences between SE and HRP over time, as well as maternal and child
      contributions to early manifestations of maternal HRP and their evolution are
      discussed.

PMID- 20137817
TI  - Differences in older people's responses to CIDI's depression screening and
      diagnostic questions may point to age-related bias.
AB  - BACKGROUND: Psychiatric surveys based on the Composite International Diagnostic
      Interview (CIDI) report very low rates of affective disorder in older people,
      perhaps because CIDI's long, convoluted screening questions present a special
      challenge to aged respondents. We have shown previously that inconsistencies in
      responses to CIDI's two screening questions about dysphoria and anhedonia rose in
      frequency with age. By contrast, responses to the short, simple K-10 and GHQ-12
      mental health scales showed much less change over the lifespan. As a check on age
      related bias, we now compare responses to CIDI's depression screening questions
      with responses to subsequent, simpler questions about other depressive symptoms.
      METHODS: Secondary analysis of an Australian national survey in which CIDI was
      administered to 10,641 adults by trained lay interviewers. RESULTS: Rates of
      positive responses to both CIDI screening questions fell from 11% in age-group 18
      34 years to 3% in respondents aged > or = 65 years. Responses to simpler CIDI
      items about other depressive symptoms and help-seeking behaviour showed much less
      change with age. CONCLUSION: Older respondents may deny symptoms when subjected
      to complex batteries of questions concerning severity, time frame, attribution
      and consequences. CIDI diagnoses need to be validated across the full age
      spectrum. LIMITATIONS: Residents of aged care facilities and those with low
      cognitive scores were excluded.

PMID- 20137818
TI  - Effect of vascular endothelial growth factor and interleukin-1beta on apoptosis
      in endometrial cell cultures from patients with endometriosis and controls.
AB  - The aim of this study was to evaluate the effect of vascular endothelial growth
      factor (VEGF) and interleukin-1beta (IL-1beta) on apoptosis induced by leuprolide
      acetate (LA) in endometrial epithelial cell cultures from patients with
      endometriosis. Primary endometrial epithelial cell cultures were obtained from
      uterine endometrial biopsies of patients with endometriosis and control women.
      Endometrial epithelial cells were incubated with LA; a combination of LA and
      VEGF; a combination of LA and IL-1beta; or in basal conditions. LA was added 3h
      prior to addition of VEGF and IL-1beta. After stimulation, the percentage of
      apoptotic cells was evaluated by the acridine orange-ethidium bromide technique
      and Bax expression was assessed by western blot. Treatment with LA enhanced the
      percentage of apoptotic cells in endometrial epithelial cells from subjects with
      endometriosis and control subjects. Addition of either VEGF or IL-1beta after
      exposure to LA restored the percentage of apoptotic cells to basal levels.
      Moreover, treatment with LA increased Bax expression in endometrial epithelial
      cells from patients with endometriosis. This effect was reverted by the addition
      of either VEGF or IL-1beta. Our results show that VEGF and IL-1beta reduce
      apoptosis and decrease Bax expression in endometrial epithelial cells from
      patients with endometriosis. This study suggests that VEGF and IL-1beta may
      protect endometriotic cells from undergoing apoptosis in addition to exerting
      their pro-angiogenic role.

PMID- 20137819
TI  - Self-rated health (SRH) as a predictor of mortality in elderly men living in a
      medium-size city in Brazil.
AB  - The objective was to examine the role of SRH as a predictor of mortality in
      elderly men in a medium-size Brazilian city. In 2 years of follow-up, 120 deaths
      occurred in the study population, with the following main causes: cardiovascular
      diseases (40%), neoplasms (22.5%), and respiratory diseases (10%). In practically
      all of the target variable strata, elderly men with fair or poor SRH showed a
      higher risk of dying as compared to those with excellent or good SRH. In the
      final model, the variables fair/poor SRH (hazard risk=HR=1.88, 95% confidence
      interval=95%CI=1.29-2.72), age (HR=1.05, 95%CI=1.03-1.08), public health system
      as the regular source of care (HR=1.69, 95%CI=1.10-2.60), current smoking
      (HR=1.94, 95%CI=1.24-3.04), and acute cardiovascular disease (HR=1.62, 95%CI=1.06
      2.47) were associated with mortality. We concluded that SRH proved to be a
      predictive variable for mortality in elderly men after 2 years of follow-up, with
      nearly a twofold risk of death among men that reported fair or poor health, after
      adjusting for age, regular use of the public health system, current smoking, and
      acute cardiovascular disease. Given the importance of poor SRH for predicting
      mortality in elderly men, health services should incorporate this indicator into
      health assessments in this population.

PMID- 20137820
TI  - Molecular analysis of bacterial population structure and dynamics during cold
      storage of untreated and treated milk.
AB  - Spoilage bacteria in milk are controlled by treatments such as thermization,
      microfiltration and addition of carbon dioxide. However, little information is
      known about the changes in microbial communities during subsequent cold storage
      of treated milk. Culture-dependent methods and a direct molecular approach
      combining 16S rRNA gene clone libraries and quantitative PCR (Q-PCR) were applied
      to obtain a better overview of the structure and the dynamics of milk microbiota.
      Raw milk samples were treated by the addition of carbon dioxide (CO(2)),
      thermization (TH) or microfiltration (MF) and stored at 4 degrees C or 8 degrees
      C up to 7d. Untreated milk (UT) was used as a control. Psychrotrophic and
      staphylococci bacteria were enumerated in the milk samples by culture methods.
      For the molecular approach, DNA was extracted from milk samples and 16S rRNA gene
      was amplified by PCR with universal primers prior to cloning. The Q-PCR method
      was used to evaluate the dynamics of dominant bacterial species revealed by clone
      library analysis of 16S rRNA gene. Comparison of the 16S rRNA gene sequence
      indicated that the two most abundant operational taxonomic units (OTU),
      determined at 97% identity, belonged to the class Gammaproteobacteria (40.3% of
      the 1415 sequences) and Bacilli (40%). Dominant bacterial species in UT, CO(2)
      and TH milk samples at day 3 were affiliated with Staphylococcus, Streptococcus,
      Clostridia, Aerococcus, Facklamia, Corynebacterium, Acinetobacter and
      Trichococcus. Dominant bacterial species detected in MF milk were
      Stenotrophomonas, Pseudomonas and Delftia, while Pseudomonas species dominated
      the bacterial population of UT, CO(2) and MF milk samples at day 7.
      Staphylococcus and Delftia were the dominant bacterial species in thermized milk.
      Q-PCR results showed that populations of S. aureus, A. viridans, A.
      calcoaceticus, C. variabile and S. uberis were stable during 7d of storage at 4
      degrees C. Populations of P. fluorescens, S. uberis and total bacteria increased
      in UT and CO(2) milk samples during 7d of storage at 8 degrees C and were
      noticeable from day 3. This study shows new microbial species which can develop
      during cold storage after milk treatment and contributes to identifying causes of
      reduced shelf life and deterioration of technological properties of milk during
      storage.

PMID- 20137821
TI  - The use of beta-adrenergic drugs improves hepatic oxygen metabolism in cirrhotic
      patients undergoing liver resection.
AB  - BACKGROUND & AIMS: Hepatic resection is associated with hemodynamic and oxygen
      metabolism disturbances of the residual liver resulting from liver regeneration.
      In underlying liver disease, the remnant liver responds inadequately to increased
      energy demands leading to a less efficient recovery process. The aim of this
      study was to assess the effect of vasoactive drugs on hepatic oxygen metabolism
      and hemodynamics in cirrhotic patients that have undergone liver resection.
      METHODS: Thirty patients were randomly allocated to receive peri-operatively low
      doses (4 microg/kg/min) of dopamine (DaG, n=10), dobutamine (DbG, n=10) or saline
      (CG, n=10). Hepatic hemodynamics, hepatic oxygen metabolism and lactate uptakes
      were evaluated before drug administration and at the time of abdominal closure.
      Post-operative liver function and outcome were recorded. RESULTS: The peri
      operative use of vasoactive drugs preserved total hepatic blood flow and hepatic
      compliance, even increasing in patients who received Db, whereas those parameters
      decreased in CG after liver resection. At this time, oxygen delivery and
      consumption decreased in CG patients, but were unchanged when vasoactive drugs
      were used. In all groups, lactate uptake decreased sharply and only DbG showed
      positive lactate extraction capacity. The peak of post-operative bilirubin, which
      resumed baseline values more quickly in DbG, inversely correlated with intra
      operative hepatic compliance and hepatic oxygen extraction. CONCLUSION: Low doses
      of vasoactive drugs, especially dobutamine, improved hepatic oxygen supply and
      uptake preserving immediate function of the remnant cirrhotic liver.

PMID- 20137822
TI  - The alphavbeta6 integrin is a highly specific immunohistochemical marker for
      cholangiocarcinoma.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are
      common primary hepatic malignancies. Their immunohistological differentiation
      using specific markers is pivotal for treatment and prognosis. We found
      alphavbeta6 integrin strongly upregulated in biliary fibrosis, but its expression
      in primary and secondary liver tumours is unknown. Here, we aimed to evaluate the
      diagnostic applicability of alphavbeta6 integrin in differentiating primary liver
      cancers. METHODS: Expression of alphavbeta6 integrin was evaluated in liver
      tissues from patients with CC, HCC, fibrolamellar HCC, combined CC/HCC, hepatic
      metastases of colorectal and pancreatic carcinomas, primary sclerosing
      cholangitis (PSC), and in human primary and tumour-derived liver cell lines by
      immunohisto- and cytochemistry, and by TaqMan PCR. Diagnostic performance of the
      beta6 subunit was compared with CK7, CK20, and HepPar 1. RESULTS: In CC cells
      beta6 mRNA levels were induced 125-fold compared to primary cholangiocytes, while
      it was completely absent in hepatoma cells. In human tissues, beta6 transcripts
      were more than 100-fold upregulated in CC compared to normal liver. By
      immunohistochemistry, 88% of CC, 50% of PSC, 13% of colorectal carcinoma
      metastases, and 80% of pancreatic carcinoma metastases presented alphavbeta6,
      whereas all HCC, combined CC/HCC and fibrolamellar HCC stained negative.
      Specificity of beta6 immunohistochemistry for CC (100%) surpassed all other
      tested markers and sensitivity was equal to CK7 (86% vs. 90%). CONCLUSION: The
      alphavbeta6 integrin is strongly expressed in human CC but not in HCC and
      therefore can be considered as a specific immunohistochemical marker in the
      differential diagnosis of primary liver tumours.

PMID- 20137823
TI  - Encephalopathy assessment in children with extra-hepatic portal vein obstruction
      with MR, psychometry and critical flicker frequency.
AB  - BACKGROUND & AIMS: Mild cognitive and psychomotor deficit has been reported in
      patients with extra-hepatic portal vein obstruction. This prospective study was
      done to ascertain the presence of minimal hepatic encephalopathy by
      neuropsychological testing and its correlation with diffusion tensor imaging
      derived metrics, T1 signal intensity, brain metabolites in (1)H magnetic
      resonance spectroscopy, blood ammonia and critical flicker frequency in patients
      with extra-hepatic portal vein obstruction. METHODS: Neuropsychological tests,
      critical flicker frequency, blood ammonia, diffusion tensor imaging, T1 signal
      intensity and (1)H magnetic resonance spectroscopy were determined in 22 extra
      hepatic portal vein obstruction and 17 healthy children. Bonferroni multiple
      comparison post hoc analysis was done to compare controls with patient groups.
      RESULTS: Based on neuropsychological tests, 7/22 patients had minimal hepatic
      encephalopathy, and significantly increased Glx/Cr ratio, blood ammonia, mean
      diffusivity and globus pallidus T1 signal intensity with decreased critical
      flicker frequency in comparison to controls and in those without minimal hepatic
      encephalopathy. Cho/Cr, mI/Cr ratio and fractional anisotropy were unchanged in
      patient groups compared to controls. A significant inverse correlation of
      neuropsychological test with mean diffusivity, Glx/Cr ratio and blood ammonia and
      a positive correlation among mean diffusivity, blood ammonia and Glx/Cr ratio was
      seen. CONCLUSIONS: Extra-hepatic portal vein obstruction is a true hyperammonia
      model with porto-systemic shunting and normal liver functions that results in
      minimal hepatic encephalopathy in one-third of these children. Hyperammonia
      results in generalized low grade cerebral edema and cognitive decline as
      evidenced by increased Glx/Cr ratio, mean diffusivity values and abnormal
      neuropsychological tests.

PMID- 20137824
TI  - Is response to antiviral treatment influenced by hepatitis B virus genotype?
AB  - Recently released clinical practice guidelines and consensus conference
      statements point to the importance of hepatitis B virus (HBV) genotyping in
      therapeutic algorithms for the treatment of chronic hepatitis B. This information
      usually comes from post hoc analyses of clinical trials which were not designed
      to study associations with the HBV genotype. We have performed a literature
      search through to April 2009 and have selected randomized clinical trials of
      currently approved anti-HBV drugs providing information on HBV genotypes and (i)
      baseline characteristics of study subjects, (ii) any response to antiviral
      therapy, (iii) interaction between HBV genotypes and the type of therapy. There
      were several intrinsic features and weaknesses in the majority of clinical trials
      conducted so far which make it difficult to reach firm conclusions about the role
      of HBV genotypes in response to antiviral therapy. Indeed, most trials were
      necessarily multicenter in order to reach a sufficient statistical power, but
      pooling together patients of different ethnicities may have revealed false
      positive associations between response to antiviral therapy and HBV genotype.
      Moreover, endpoint definitions, especially for the composite ones, varied
      substantially among studies, leading to lack of homogeneity. Finally, possible
      interactions between the type of therapy and the HBV genotype were only seldom
      analysed. The present review highlights several caveats regarding current
      indications proposed by the major clinical practice guidelines and consensus
      conference statements published thus far and emphasise the need for further long
      term studies in the field.

PMID- 20137825
TI  - A longitudinal analysis of innate and adaptive immune profile during hepatic
      flares in chronic hepatitis B.
AB  - BACKGROUND & AIMS: The pathogenesis of hepatic flares (HF) in patients
      chronically infected with hepatitis B virus (HBV) is controversial. Therefore, we
      studied the kinetics of innate and adaptive immune activation during HF in
      chronic hepatitis B. METHODS: Soluble (IFN-alpha, IL-1beta, TNF-alpha, IL-6, IL
      8, IL-10, CCL-2, CCL-3, CXCL-9, CXCL-10) and cellular (HBV-specific T cells, NK,
      Treg) immunological parameters were measured longitudinally (10 month-4 week
      intervals) in patients (n=5) who developed HF after therapy withdrawal and cross
      sectionally in chronic (n=29) and acute hepatitis B patients (n=5). Hepatic
      expression of different chemokines was studied by co-incubating cytokines (IFN
      alpha, IFN-gamma, TNF-alpha) and activated T, NK and monocytes with hepatocytes
      and hepatocyte-like cells. RESULTS: A progressive increase of HBV replication
      precedes HF but occurs without detection of innate immune activation, with the
      exception of increased serum CXCL-8. Despite the absence of increased circulatory
      HBV-specific T or activated NK cells, HF were temporally associated with high
      serum levels of IFN-gamma inducible chemokines CXCL-9 and CXCL-10 (but not CCL-2
      or CCL-3). CXCL-9 and CXCL-10 displayed different in vitro requirements for
      activation and are differentially produced in liver injury present in acute or
      chronic patients. CONCLUSIONS: CXCL-9 and CXCL-10 play a major role in the
      development of HF. Their differential expression in acute versus chronic patients
      suggests the presence of different mechanisms that govern liver injury during
      acute and chronic hepatitis B.

PMID- 20137826
TI  - Pandemic planning in pediatric care: a website policy review and national survey
      data.
AB  - OBJECTIVES: This study investigates current policies, key issues, and needs for
      pandemic planning in pediatrics in Canada. METHODS: Online pandemic plans from
      national, provincial and territorial government websites were reviewed to
      identify: plans for children and families, and psychosocial and ethical issues. A
      survey was administered to gather participants' perspectives on the needs in
      pediatric planning, as well as important elements of their organizations' and
      regions' pandemic plans. A thematic analysis was conducted on qualitative survey
      responses. RESULTS: The majority of existing plans did not adequately address the
      unique needs of pediatric populations, and mainly focused on medical and policy
      concerns. Several gaps in plans were identified, including the need for
      psychosocial supports and ethical decision-making frameworks for children and
      families. Similarly, survey respondents identified parallel gaps, in their
      organization's or region's plans. CONCLUSIONS: Although many plans provide
      guidelines for medical and policy issues in pediatrics, much more work remains in
      psychosocial and ethical planning. A focus on children and families is needed for
      pandemic planning in pediatrics to ensure best outcomes for children and
      families.

PMID- 20137827
TI  - Orofacial granulomatosis: clinical features and long-term outcome of therapy.
AB  - BACKGROUND: Orofacial granulomatosis (OFG) is a chronic inflammatory disorder
      characterized by persistent or recurrent soft tissue enlargement, oral
      ulceration, and a variety of other orofacial features. There remain few detailed
      reports of the clinical features and long-term response to therapy of substantial
      groups of patients with OFG. OBJECTIVE: The aim of this study was to determine
      retrospectively the clinical, hematologic, and histopathological features of a
      large case series of patients with OFG. In addition the long-term response to
      therapy was examined. METHODS: Clinically relevant data of 49 patients with OFG
      who attended a single oral medicine unit in the United Kingdom were
      retrospectively examined. The analyzed parameters included diagnostic features,
      clinical manifestations, and outcomes and adverse side effects of therapy.
      RESULTS: Labial swelling was the most common presenting clinical feature at
      diagnosis (75.5%), followed by intraoral mucosal features other than ulceration
      such as cobblestoning and gingival enlargement (73.5%). Mucosal ulceration was
      observed in 36.7% of patients whereas extraoral facial manifestations such as
      cutaneous erythema and swelling were present in 40.8% of patients. Of the 45
      patients who required treatment, 24 (53.3%) were treated with topical
      corticosteroids/immunosuppressants only, whereas 21 (46.7%) received a combined
      therapy (topical plus systemic corticosteroids/immunosuppressants and/or
      intralesional corticosteroids). The long-term outcome analysis showed
      complete/partial resolution of tissue swelling and oral ulceration in 78.8% and
      70% of patients, respectively. LIMITATIONS: The main limitation of the current
      study was its retrospective design and methodology including differences in
      reporting clinical features and outcome. CONCLUSIONS: OFG can show multiple
      facial and mucosal clinical features. Long-term treatment with topical and/or
      combined therapy is needed in the majority of patients. Response to therapy is
      highly variable even though in the long-term complete/partial disease resolution
      can be obtained in the majority of patients. Mucosal ulceration tends to be more
      recalcitrant than orofacial swelling. Adverse side effects of therapy are rare.

PMID- 20137828
TI  - Survey of employee knowledge and attitudes before and after a multicenter
      Veterans' Administration quality improvement initiative to reduce nosocomial
      methicillin-resistant Staphylococcus aureus infections.
AB  - BACKGROUND: Although guidelines currently recommend prevention practices to
      decrease in-hospital transmission of infections, increasing adherence to the
      practices remains a challenge. This study assessed the effect of a multicenter
      methicillin-resistant Staphylococcus aureus (MRSA) prevention initiative on
      changes in employees' knowledge, attitudes, and practices. METHODS: Two cross
      sectional surveys were distributed at baseline (October 2006) and follow-up (July
      2007) at 17 medical centers participating in the Veterans' Administration (VA)
      MRSA initiative. RESULTS: Surveys were completed by 1362 employees at baseline
      and 952 employees at follow-up (representing 57% and 56% of eligible respondents,
      respectively). Respondents included physicians (9%), nurses (38%), allied health
      professionals (30%), and other support staff (24%). Of the 5 knowledge items, the
      mean proportion answered correctly increased slightly from baseline to follow-up
      (from 71% to 73%; P = .07). The percentage of respondents who believed that MRSA
      was a problem on their unit increased over time (from 56% to 65%; P < .001).
      Respondents also reported increased comfort with reminding other staff about
      proper hand hygiene (from 61% to 70%; P < .001) and contact precautions (from 63%
      to 70%; P < .002). The percentage of respondents reporting at least one barrier
      to proper hand hygiene decreased over time (from 25% to 20%; P = .003).
      CONCLUSIONS: In this multicenter study of VA employees, implementation of a MRSA
      quality improvement initiative was associated with temporal improvements in
      knowledge and perceptions regarding MRSA prevention.

PMID- 20137829
TI  - A multimodal approach to central venous catheter hub care can decrease catheter
      related bloodstream infection.
AB  - BACKGROUND: This study was conducted to investigate decreases in catheter-related
      bloodstream infections (CRBSIs) through an evidence-based multimodal
      intervention. METHODS: This was a prospective interventional study of neonates
      with a central venous catheter (CVC) from a neonatal intensive care unit
      database, involving implementation of a multimodal approach to central venous
      catheter hub care using 2% chlorhexidine in 70% isopropyl alcohol and education
      of medical staff by audiovisual presentations. CRBSI rates in the pre
      intervention period and postintervention period were compared. RESULTS: A total
      of 373 patients with a CVC (163 in the preintervention period and 210 in the
      postintervention period) were studied. Patient demographic and clinical
      characteristics were similar in the 2 periods. Extremely low birth weight infants
      constituted 40% of the cohort in the preintervention period and 38% of the cohort
      in the postintervention period. The CRBSI rate in patients with a umbilical
      artery catheter and an umbilical vein catheter decreased from 15/1000 catheter
      days to 10/1000 catheter-days (odds ratio [OR], 0.47; 95% confidence interval
      [CI], 0.17-0.91). The CRBSI rate in patients with a peripherally inserted central
      catheter decreased from 23/1000 catheter-days to 10/1000 catheter-days (OR, 0.33;
      95% CI, 0.12-0.91). These decreased CRBSI rates were sustained despite high
      device utilization. The incidence of gram-negative septicemia also decreased. Ten
      CRBSIs were prevented by this multimodal approach, representing significant
      health care cost savings. CONCLUSION: This study demonstrates significant
      decreases in CRBSI rate for all catheter types and birth weight categories
      associated with the multimodal intervention. Audiovisual education is an
      effective tool for practice change. Reeducation and compliance monitoring should
      be part of all nosocomial infection prevention strategies, resulting in
      significant savings in health care costs.

PMID- 20137830
TI  - Telomere shortening is associated to TRF1 and PARP1 overexpression in Duchenne
      muscular dystrophy.
AB  - Telomere shortening is thought to contribute to premature senescence of satellite
      cells in Duchenne muscular dystrophy (DMD) muscle. Telomeric repeat binding
      factor-1 (TRF1) and poly (ADP-ribose) polymerase-1 (PARP1) are proteins known to
      modulate telomerase reverse transcriptase (TERT) activity, which controls
      telomere elongation. Here we show that an age-dependent telomere shortening
      occurs in DMD muscles and is associated to overexpression of mRNA and protein
      levels of TRF1 and PARP1. TERT expression and activity are detectable in normal
      control muscles and they slightly increase in DMD. This is the first
      demonstration of TRF1 and PARP1 overexpression in DMD muscles. They can be
      directly involved in replicative senescence of satellite cells and/or in the
      pathogenetic cascade through a cross-talk with oxidative stress and inflammatory
      response. Modulation of these events by TRF1 or PARP1 inhibition might represent
      a novel strategy for treatment of DMD and other muscular dystrophies.

PMID- 20137831
TI  - A lifespan MRI evaluation of ventricular enlargement in normal aging mice.
AB  - Ventricular enlargement has been proposed as a structural biomarker for the
      progression of Alzheimer's disease (AD). This biomarker, established in human
      patients, needs to be translated to animals to facilitate drug development for
      the disease. However, ventricular enlargement is not exclusive to AD, since the
      ventricle size increases during normal aging. A longitudinal characterization of
      ventricular enlargement in normal aging in mice is therefore crucial before
      further evaluations of mouse models or neurodegenerative diseases associated to
      brain atrophy. To this end, ventricular enlargement in normal aging mice was
      characterized over the lifespan (i.e., 2 years). The results showed that the
      overall ventricle size increased with age, with the expansion beginning during
      the early life stages and continuing to old age. The reported data represent a
      biomarker benchmark for normal aging mice under unmodified conditions. This
      provides a foundation for evaluating the validity of AD mouse models or the
      effects of potential drugs. The considerable physiological ventricular
      enlargement during normal aging must be considered in related experiments.

PMID- 20137832
TI  - [Pulmonary air embolism as a complication of central venous catheter].

PMID- 20137833
TI  - [False positive in pelvis in a PET-CT scan due to ovarian reimplantation: a case
      report].
AB  - We present the case of a 36-year-old premenopausal woman with a background of
      surgically-treated cervical neoplasm. She underwent a positron emission
      tomography-computed tomography (PET-CT) for evaluation of the new appearance of
      abnormal inguinal lymph nodes. The study showed two hypermetabolic nodules in the
      pelvic region suggestive of corresponding to an implant and to tumor involvement
      of the lymph node, respectively. After a clinical evaluation and a new PET-CT
      scan, it was considered that these uptake foci corresponded to physiological
      activity of the FDG secondary to ovarian activity in a patient with ovariopexy.
      This article shows the importance of having complete clinical information about
      the patients before evaluating the studies. We also present a review of the
      medical literature on the cervical neoplasm and metabolic behavior of the adnexa
      in relationship with the menstrual cycle of pre-menopausal women.

PMID- 20137834
TI  - Design, synthesis and biological evaluation of indane-2-arylhydrazinylmethylene
      1,3-diones and indol-2-aryldiazenylmethylene-3-ones as beta-amyloid aggregation
      inhibitors.
AB  - Biological screening of (hetero)aromatic compounds allowed the identification of
      some novel inhibitors of Abeta(1-40) aggregation, bearing indane and indole rings
      as common scaffolds. Molecular decoration of lead compounds led to inhibitors
      exhibiting a potency, measured by the Thioflavin T fluorimetric assay, ranging
      from high to low micromolar IC(50). The 2-(p
      isopropylphenyldiazenylmethylene)indolone derivative 6c resulted as the most
      potent aggregation inhibitor exhibiting an IC(50) of 1.4 muM, with complete lack
      of fibril formation as confirmed by transmission electron microscopy. Structure
      activity relationships suggested that binding to the Abeta peptide may be largely
      guided by pi-stacking and hydrogen bond interactions.

PMID- 20137835
TI  - Novel quinoline and naphthalene derivatives as potent antimycobacterial agents.
AB  - We have designed and synthesized both the quinoline and naphthalene based
      molecules influenced by the unique structural make-up of mefloquine and TMC207,
      respectively. These compounds were evaluated for their anti-mycobacterial
      activity against drug sensitive Mycobacterium tuberculosis H37Rv in vitro at
      single-dose concentration (6.25 microg/mL). The compounds 22, 23, 26 and 27
      inhibited the growth of M. tuberculosis H37Rv 99%, 90%, 98% and 91% respectively.
      Minimum inhibitory concentration of compounds 22, 23, 26 and 27 was found to be
      6.25 microg/mL. Our molecular modeling and docking studies of designed compounds
      showed hydrogen bonding with Glu-61, Tyr-64 and Asn-190 amino acid residues at
      the putative binding site of ATP synthase, these interactions were coherent as
      shown by Mefloquine and TMC207, where hydrogen bonding was found with Tyr-64 and
      Glu-61 respectively. SAR analysis indicates importance of hydroxyl group and
      nature of substituents on piperazinyl-phenyl ring was critical in dictating the
      biological activity of newly synthesized compounds.

PMID- 20137836
TI  - Mechanistic aspects of transport antibiotics.
AB  - Ab initio molecular orbital calculations at the Hartree Fock level have been
      performed on transport antibiotics. Conformational aspects together with
      electrostatic interactions play a role in determining efficient transport
      properties of these compounds. Our results indicate that cytotoxicity of nactins
      may be related to their highly reorganized ionophore in presence of ion leading
      to tightly bound ion that cannot be delivered at site of action. Mechanistic
      aspects discussed in this study will enable efficient designing of compounds with
      more drug like features and prospective usage as immunosuppressants.

PMID- 20137837
TI  - Synthesis, biological evaluation and molecular docking of novel series of spiro
      [(2H,3H) quinazoline-2,1'- cyclohexan]-4(1H)- one derivatives as anti
      inflammatory and analgesic agents.
AB  - Three series of Spiro [(2H,3H) quinazoline-2,1'-cyclohexan]-4(1H)-one derivatives
      have been synthesized. Some of the novel quinazolinone derivatives IIe, VIIIc,
      XIc, XIIb, XIIc, XVIb showed considerable potent anti-inflammatory and analgesic
      activity of superior G.I.T. safety profile in experimental rats in comparing to
      indomethacin and tramadol as reference drugs. Docking study into COX-2 has been
      made for derivatives of highest anti-inflammatory activity. The compound XVIb
      showed the nearest RMSD value to that of indomethacin.

PMID- 20137838
TI  - The Scottish Trial of Refer or Keep (the STORK study): midwives' intrapartum
      decision making.
AB  - OBJECTIVES: to explore midwives' intrapartum referral decisions in relation to
      their dispositional attitude towards risk. DESIGN: a web-based correlation study
      examined the association between midwife's personality (personal risk tendency),
      place of work (location), years of experience and the timing of their decisions
      to make referrals (referral score) in a series of fictitious case scenarios
      (vignettes). PARTICIPANTS: 102 midwives providing labour care in both consultant
      led units (CLU) and community maternity units (CMU) from four Scottish health
      board areas. ANALYSIS: a correlational analysis was carried out to test the
      association between total risk scores and midwives' referral scores. Between
      group comparisons were also conducted for experienced vs inexperienced midwives,
      midwives practising in CLU vs CMU settings and between the four health board
      areas. FINDINGS: despite being presented with identical information in the
      vignettes, midwives made a wide range of referral decisions. There was no
      association between referral scores and measures of risk, personality or years of
      experience. No statistically significant difference between the referral scores
      of midwives working in CLUs or CMUs was observed. However, a statistically
      significant difference did emerge between the four health board areas, with
      midwives from one area making referrals at a significantly earlier stage. The
      maternity services in this area had experienced several high profile adverse
      events prior to this study; this may have influenced their referral behaviour
      (the availability heuristic), in terms of making more cautious decisions. KEY
      CONCLUSIONS: there was no evidence that variability in the range of referral
      decisions was due to personality factors, risk propensity, experience or whether
      the midwife worked in a CLU or CMU. Local factors such as recent adverse events
      may significantly influence subsequent referral behaviour. Further research is
      required to identify why the midwives showed so much unexplained variability in
      their responses to the vignettes.

PMID- 20137839
TI  - A competitive indirect enzyme-linked immunoassay for lead ion measurement using
      mAbs against the lead-DTPA complex.
AB  - Immunoassays for quantitative measurement of environmental heavy metals offer
      several advantages over other traditional methods. To develop an immunoassay for
      lead, Balb/c mice were immunized with a lead-chelate-protein conjugate to allow
      maximum exposure of the metal to the immune system. Three stable hybridoma cell
      lines were obtained through spleen cells fusion with Sp2/0 cells. One cell line,
      2A11D11, produced mAbs with preferential selectivity and sensitivity for Pb-DTPA
      than DTPA, exhibiting an affinity constant of 3.34 + or - 0.24 x 10(9) M(-1).
      Cross reactivity (CR) with other metals were below 1%, except for Fe(III) with a
      CR less than 5%. This quantitative indirect ELISA for the lead ion was used to
      detect environmental lead content in local water sources; importantly, the
      results from the immunoassay were in excellent agreement with those from ICP-MS.
      Development of immunoassays for metal ions may thus facilitate the detection and
      regulation of environmental pollution.

PMID- 20137840
TI  - Reappraisal of the impact of race on survival in patients on dialysis.
AB  - Racial differences in the cause, natural history, and effects of chronic kidney
      disease have long been the subject of investigation. Dialysis-dependent kidney
      failure occurs nearly 4 times more often in African Americans than European
      Americans. Despite this observation, studies repeatedly show that African
      Americans have a significant survival advantage after initiating dialysis
      therapy. Although this phenomenon has been attributed to environmental and
      socioeconomic factors, recent studies show that inherited factors strongly
      influence racial differences in the development of diverse kidney diseases and
      may affect the risk of nephropathy-associated cardiovascular disease. We review
      relevant studies and propose the hypothesis that inherited factors leading to
      organ-limited kidney diseases and a lower burden of systemic atherosclerosis
      contribute in part to the improved survival rates in African American patients on
      dialysis therapy.

PMID- 20137841
TI  - Assessment of positive functioning in clinical psychology: theoretical and
      practical issues.
AB  - Positive psychology has led to an increasing emphasis on the promotion of
      positive functioning in clinical psychology research and practice, raising issues
      of how to assess the positive in clinical setting. Three key considerations are
      presented. First, existing clinical measures may already be assessing positive
      functioning, if positive and negative functioning exist on a single continuum
      (such as on bipolar dimensions from happiness to depression, and from anxiety to
      relaxation). Second, specific measures of positive functioning (e.g., eudemonic
      well-being) could be used in conjunction with existing clinical scales. Third,
      completely different measures would be needed depending on whether well-being is
      defined as emotional or medical functioning, or as humanistically orientated
      growth (e.g., authenticity). It is important that clinical psychologists
      introduce positive functioning into their research and practice in order to widen
      their armoury of therapeutic interventions, but in doing so researchers and
      practitioners need also to be aware that they are shifting the agenda of clinical
      psychology. As such, progress in clinical psychology moving toward the adoption
      of positive functioning requires reflection on epistemological foundations.

PMID- 20137842
TI  - Lifecourse socioeconomic trajectories and C-reactive protein levels in young
      adults: findings from a Brazilian birth cohort.
AB  - Socioeconomic factors are associated with cardiovascular disease. C-reactive
      protein (CRP) is increasingly implicated as a candidate linking conventional risk
      factors and atherosclerosis. The impact of early- and later-life socioeconomic
      status (SES) on CRP levels has not been widely investigated and a handful of
      studies from high-income countries are inconsistent. We set out to examine the
      associations between lifecourse socioeconomic indicators (family income at birth,
      maternal education, family income at age 23 and own education) on CRP levels in
      young adults belonging to the 1982 Pelotas (Brazil) Birth Cohort Study (n=5914).
      Early-life SES showed significant and graded associations with CRP levels at age
      23 independently of later SES. For example, men with higher family income at
      birth showed higher CRP levels at age 23 (p=0.001 for trend) and women with less
      educated mothers showed higher CRP levels (p=0.01 for trend). Notably,
      differential directions of association between SES indicators and CRP levels
      between men and women were found. When adjusted for SES at age 23, men with the
      lowest family income at birth showed 42% lower CRP levels when compared to men in
      the highest family income group (-42; 95% CI: -60,-16). In contrast women born to
      the least educated mothers had the highest CRP levels (35; 95% CI -2, 86). In
      both sexes, adiposity accounted for the overwhelming majority of the associations
      between SES and CRP levels. Sex and gender roles specific to middle-income
      countries, socio-cultural and environmental conditions that may impact adiposity,
      and the level of epidemiological transition may be key factors that are linked to
      the associations between lifecourse SES and CRP levels. Public health strategies
      aimed at decreasing the burden of cardiovascular disease in middle-income
      settings, in addition to highlighting the risks associated with adult obesity,
      should not overlook the wide-ranging impacts of lifecourse social determinants.

PMID- 20137843
TI  - The numbers, educational status and health of enrolled and non-enrolled school
      age children in the Allai Valley, Northwest Frontier Province, Pakistan.
AB  - A cluster survey of the age, sex and enrolment status of all school-age children
      5-14 years old was undertaken in 2006 in a remote rural sub-district of the
      Northwest Frontier Province, Pakistan about a year after a devastating
      earthquake. Information was collected on the characteristics of children, their
      households and parents, and on reasons for non-enrolment. The health and
      nutritional status of a randomly selected child in each household was assessed
      and enrolled and non-enrolled children were compared by sex. A total of 2032
      children were recorded in 925 households, 845 girls and 1187 boys, a sex ratio of
      71 girls/100 boys. Half of all girls were not enrolled in school compared with a
      fifth of all boys. There was no common reason for non-enrolment and they differed
      between the sexes. The randomly selected children (n = 897) were moderately
      malnourished: 43% were stunted, 12% were thin and 46% were anaemic. 66% of a sub
      sample of children (n = 269) had a low urinary iodine concentration, which could
      contribute to a low IQ and impaired hearing. There were no statistically
      significant differences in the nutritional status or health of non-enrolled and
      enrolled girls. These data contribute towards an understanding of how to improve
      the education and health of school-age children in a conservative, rural province
      of Pakistan.

PMID- 20137844
TI  - Is the "practice style" hypothesis relevant for general practitioners? An
      analysis of antibiotics prescription for acute rhinopharyngitis.
AB  - Much research in France or abroad has highlighted the medical practice variation
      (MPV) phenomenon. There is no consensus on the origin of MPV between preference
      centered approaches versus opportunities and constraints approaches. This study's
      main purpose is to assess the relevance of hypotheses which assume that
      physicians adopt a uniform practice style for their patients for each similar
      clinical decision in a context of medical decision with low uncertainty and
      professional practice with weak regulation. Multilevel models are evaluated:
      first to measure variability of antibiotics prescription by French general
      practitioners (GPs) for acute rhinopharyngitis regarding clinical guidelines, and
      to test its significance in order to determine to what extent prescription
      differences are due to between or within GPs discrepancies; second, to prioritize
      its determinants, especially those relating to a GP or his/her practice setting
      environment, while controlling visit or patient confounders. The study was based
      on 2001 activity data, along with an ad hoc questionnaire, of a sample of 778 GP
      taken from a panel of 1006 computerized French GPs. We observed that a large part
      of the total variation was due to intra-physician variability (70%). It is
      patient characteristics that largely explain the prescription, even if GP or
      practice setting characteristics (location, level of activity, network
      participation, continuing medical education) and environmental factors (visit
      from pharmaceutical sales representatives) also exert considerable influence.
      This suggests that MPV are partly caused by differences in the type of
      dissemination of medical information and this may help policy makers to identify
      and develop facilitators for promoting better use of antibiotics in France and,
      more generally, for influencing GP practices when it is of interest.

PMID- 20137845
TI  - Some unintended effects of teamwork in healthcare.
AB  - Teamwork has been emphasised as a key feature of health service reform, essential
      for safe, efficient and patient-centred care. Bringing together literatures from
      the sociology of healthcare and organizational theory, we examine how the
      teamwork phenomenon plays out in practice. Drawing upon material from two
      ethnographic studies, conducted in an operating theatre and a medical-records
      department in separate UK NHS hospitals, we explore some of the discursive
      teamwork practices of healthcare staff. Our analysis presents a very different
      picture from the normative, evangelistic promotion of teamwork within much
      management and health policy writing. We reveal how the ambiguity of teamwork
      opens up opportunities for a complex, diverse range of responses to the
      managerial discourse among diverse occupational groups, mobilizing the discourse
      to enact identity in different ways. We highlight how teamwork discourse can be
      instrumentally co-opted in the reproduction of the very occupational divisions it
      is designed to ameliorate, or simply ignored as irrelevant when compared to more
      attractive forms of collective identity. These responses challenge both those who
      believe that teamwork is a solution to problems in healthcare, as well as those
      concerned about the oppressive effects of pervasive managerialism.

PMID- 20137846
TI  - Understanding factors influencing substance use in people with recent onset
      psychosis: A qualitative study.
AB  - This qualitative study identifies factors influencing the use of substances in
      young people with recent onset psychosis. A purposive sample of 19 people aged
      between 16 and 35 years from an Early Intervention Service in the English
      National Health Service (NHS) was interviewed using a semi-structured guide. All
      had experienced a psychotic episode and were within 3 years of first contact with
      the service. All were either currently misusing substances or had been doing so
      in the 6 months prior to first contact with the service. All participants
      were/had been regular cannabis users and for 13(68%) cannabis was the primary
      drug of use. Thematic analysis identified four key themes in participants
      accounts of factors influencing their substance abuse: influence of perceived
      drug norms on behaviour; attributions for initial and ongoing drug-taking
      behaviour; changes in life goals affecting drug use; beliefs about the links
      between mental health and drug use. These findings have clear implications for
      interventions at a number of levels to support young people using substances in
      early psychosis including public health messages, education and psychological
      therapies.

PMID- 20137847
TI  - Success in health information exchange projects: solving the implementation
      puzzle.
AB  - Interest in health information exchange (HIE), defined as the use of information
      technology to support the electronic transfer of clinical information across
      health care organizations, continues to grow among those pursuing greater patient
      safety and health care accessibility and efficiency. In this paper, we present
      the results of a longitudinal multiple-case study of two large-scale HIE
      implementation projects carried out in real time over 3-year and 2-year periods
      in Quebec, Canada. Data were primarily collected through semi-structured
      interviews (n=52) with key informants, namely implementation team members and
      targeted users. These were supplemented with non-participants observation of team
      meetings and by the analysis of organizational documents. The cross-case
      comparison was particularly relevant given that project circumstances led to
      contrasting outcomes: while one project failed, the other was a success. A risk
      management analysis was performed taking a process view in order to capture the
      complexity of project implementations as evolving phenomena that are affected by
      interdependent pre-existing and emergent risks that tend to change over time. The
      longitudinal case analysis clearly demonstrates that the risk factors were
      closely intertwined. Systematic ripple effects from one risk factor to another
      were observed. This risk interdependence evolved dynamically over time, with a
      snowball effect that rendered a change of path progressively more difficult as
      time passed. The results of the cross-case analysis demonstrate a direct
      relationship between the quality of an implementation strategy and project
      outcomes.

PMID- 20137848
TI  - Conflict between the work and family domains and exhaustion among vocationally
      active men and women.
AB  - Exhaustion is consistently found to be more prevalent in women than in men. Women
      suffer from job strain more often, which may constitute a partial explanation for
      this phenomenon, but experienced shortcomings in combining work and family
      demands may also contribute to ill health. The aim of this study was to
      investigate, and analyse by gender, how work-related and family-related factors,
      as well as the interface between them, i.e. work-to-family conflict (WFC) and
      family-to-work conflict (FWC), are related to exhaustion. The study was cross
      sectional with self-administered questionnaires assessing exposures and outcome
      with previously well-validated instruments. The participants were 2726 men and
      2735 women, aged 45-64, vocationally active, and residing in Malmo, Sweden.
      Sixteen percent of the women and 8% of the men considered themselves exhausted.
      WFC, FWC, job strain, and low job support were all strongly correlated to
      exhaustion in both genders. In the multivariate analyses, adjusting for other
      work and family risk factors, WFC and FWC remained statistically significant risk
      factors for exhaustion in both men and women. Job strain, low job support, and
      having a somatic disorder were also independently associated with exhaustion.
      While WFC was more prevalent among men, it was more strongly associated with
      exhaustion in women than in men. In women, WFC and FWC contributed to a larger
      part of the explanatory power of the model, which amounted to 22% of the variance
      in women and 14% in men. The results imply that the concept of 'work stress'
      should be regarded in a wider context in order to understand gender related
      issues of exhaustion among vocationally active individuals.

PMID- 20137849
TI  - Differential patient-caregiver opinions of treatment and care for advanced lung
      cancer patients.
AB  - This study examined the differences of opinion between cancer patients and
      caregivers with regard to treatment and care decisions. 184 advanced lung cancer
      patients and 171 primary caregivers were recruited as a convenience sample from
      hospitals in Cleveland, Ohio. A telephone interview was conducted to collect data
      using a semi-structured questionnaire. Nonparametric tests and regression
      analysis were performed. The findings showed that patients and caregivers
      reported significant disagreement on three main issues: trade-off between
      treatment side effects and benefits; reporting treatment side effects to
      physicians, and hospice care. Caregivers were more concerned about patient's
      quality of life and more willing to discuss hospice issues than were patients (p
      < or = 01). Perceived family disagreement is associated with depression in both
      patients and caregivers (p < or = 01; R(2)=8%). The study provided empirical
      evidence for patient-caregiver disagreement about treatment and care decisions
      and its significant adverse impact on both patients and caregivers.

PMID- 20137850
TI  - Retrospective evaluation of the outcome of open versus laparoscopic adrenalectomy
      for stage I and II adrenocortical cancer.
AB  - BACKGROUND: Although there is consensus that laparoscopy is the standard of care
      for the resection of benign adrenal tumours, there is controversy regarding the
      role of laparoscopy for the resection of adrenocortical cancer (ACC). OBJECTIVE:
      The aim of the present study was to review the ACC database of the San Luigi
      Hospital to compare the oncologic effectiveness of open adrenalectomy (OA) versus
      laparoscopic adrenalectomy (LA) in the treatment of patients with stage I and II
      ACC. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective analysis
      involving 43 patients with stage I and II ACC who had undergone radical surgery.
      INTERVENTION: The patients were stratified into two groups according to the
      surgical procedure. The "open group" consisted of patients treated with OA; the
      "lap group" consisted of patients treated with LA. MEASUREMENTS: Oncologic
      effectiveness of the procedures was tested comparing the recurrence-free survival
      of patients treated with OA versus LA. Secondary outcome measures were
      differences in terms of type of recurrence and overall survival. RESULTS AND
      LIMITATIONS: The open group consisted of 25 patients and the lap group of 18
      patients. The two groups were comparable in terms of demographic data. The median
      follow-up was 38 mo in the open group and 30 mo in the lap group. Recurrence rate
      was 64% in the open group and 50% in the lap group. The median recurrence-free
      survival was 18 mo in the open group and 23 in the lap group (p=0.8). No
      differences in terms of pattern of recurrences were recorded. During follow-up,
      28% of the open group patients and 5% of the lap group patients died. No
      differences in terms of survival time were noted (p=0.3). CONCLUSIONS: The
      present findings provide interesting evidence that OA and LA may be comparable in
      terms of recurrence-free survival for patients with stage I and II ACC when the
      principles of surgical oncology are respected.

PMID- 20137852
TI  - Giant posterior fossa arachnoid cyst associated with syringomyelia.

PMID- 20137853
TI  - TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk
      factors in renal-cell carcinoma from central and eastern Europe.
AB  - Renal-cell carcinomas (RCC) are frequent in central and eastern Europe and the
      reasons remain unclear. Molecular mechanisms, except for VHL, have not been much
      investigated. We analysed 361 RCCs (334 clear-cell carcinomas) from a multi
      centre case-control study for mutations in TP53 (exons 5-9 in the whole series
      and exons 4 and 10 in a pilot subset of 60 tumours) and a pilot 50 tumours for
      mutations in EGFR (exons 18-21) or KRAS (codon 12) in relation to VHL status.
      TP53 mutations were detected in 4% of clear-cell cases, independently of VHL
      mutations. In non-clear-cell carcinomas, they were detected in 11% of VHL-wild
      type tumours and in 0% of tumours with VHL functional mutations. No mutations
      were found in EGFR or KRAS. We conclude that mutations in TP53, KRAS, or EGFR are
      not major contributors to the RCC development even in the absence of VHL
      inactivation. The prevalence of TP53 mutations in relation to VHL status may
      differ between clear-cell and other renal carcinomas.

PMID- 20137854
TI  - Pem renders tumor cells resistant to apoptotic cell death induced by a CD8+ T
      cell-mediated immune response or anticancer drug treatment.
AB  - Pem, a member of homeobox genes, is an oncofetal gene which is preferentially
      expressed in reproductive tissues and in multiple tumor cell lines. However, the
      function of Pem in tumor cell lines has not been elucidated. Herein we report
      that the ectopic expression of Pem in TC-1, a human papillomavirus type 16 (HPV
      16) E7-expressing surrogate cervical tumor cell line, demonstrated a significant
      increase in extracellular signal-regulated kinase (ERK) activity and multiple
      resistance to various apoptotic pressures from an E7-specific CD8(+) T cell
      mediated immune response and anticancer drug treatment. The observed resistance
      to apoptotic death of the Pem-over-expressing TC-1 tumor cells (TC-1/Pem) was
      associated with the down-regulation of a pro-apoptotic molecule, such as BIM, and
      up-regulation of an anti-apoptotic molecule, such as Bcl-2 protein, which
      mediated ERK activation. We also observed that the intratumoral injection of an
      ERK inhibitor enhanced the therapeutic efficacy of E7-specific CD8(+) T cell
      adoptive transfer or anticancer drug treatment against the resistant TC-1/Pem
      tumor. This is the first evidence demonstrating an association between Pem and a
      signaling pathway, namely the ERK-mediated survival signal transduction pathway.
      Thus, our data indicate that activation of the ERK pathway represents a new
      mechanism of Pem-mediated multiple resistances and the present research will
      contribute to the development of a novel strategy in cancer therapy against Pem
      over-expressing tumor cells.

PMID- 20137855
TI  - Synergistic antitumor effect of TRAIL in combination with sunitinib in vitro and
      in vivo.
AB  - The present data showed that sunitinib potentiated the in vitro and in vivo
      anticancer capabilities of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL), also known as Apo2 ligand. Interactions between sunitinib and
      TRAIL were examined in colon cancer SW620 cells and lung cancer 95-D cells. The
      average combination index (CI) values of the anti-proliferation abilities on each
      cancer cell line were less than 1.0, demonstrating the synergism of the
      combination of sunitinib and TRAIL. Western blot experiments indicated that TRAIL
      and sunitinib synergistically enhanced apoptosis by simultaneously activating the
      extrinsic and intrinsic pathways. The decrease in the expression levels of anti
      apoptotic proteins cFLIP, XIAP and Mcl-1 were probably involved in this apoptosis
      enhancement. Furthermore, treatment of colon cancer SW620-bearing nude mice with
      sunitinib plus TRAIL resulted in more significant tumor growth inhibition
      (52.8%), comparing with the moderate inhibition in TRAIL-treated (35.3%) or
      sunitinib-treated groups (26.7%) (p<0.05). These results indicate that the
      combination of TRAIL with sunitinib seems highly encouraging and warrants further
      investigation in a clinical setting.

PMID- 20137856
TI  - Dihydroartemisinin inactivates NF-kappaB and potentiates the anti-tumor effect of
      gemcitabine on pancreatic cancer both in vitro and in vivo.
AB  - Gemcitabine is currently the best known chemotherapeutic option available for
      pancreatic cancer, but the tumor returns de novo with acquired resistance over
      time, which becomes a major issue for all gemcitabine-related chemotherapies. In
      this study, for the first time, we demonstrated that dihydroartemisinin (DHA)
      enhances gemcitabine-induced growth inhibition and apoptosis in both BxPC-3 and
      PANC-1 cell lines in vitro. The mechanism is at least partially due to DHA
      deactivates gemcitabine-induced NF-kappaB activation, so as to decrease
      tremendously the expression of its target gene products, such as c-myc, cyclin
      D1, Bcl-2, Bcl-xL. In our in vivo studies, gemcibabine also manifested remarkably
      enhanced anti-tumor effect when combined with DHA, as manifested by significantly
      increased apoptosis, as well as decreased Ki-67 index, NF-kappaB activity and its
      related gene products, and predictably, significantly reduced tumor volume. We
      concluded that inhibition of gemcitabine-induced NF-kappaB activation is one of
      the mechanisms that DHA dramatically promotes its anti-tumor effect on pancreatic
      cancer.

PMID- 20137857
TI  - Parameters optimization of rice husk ash (RHA)/CaO/CeO2 sorbent for predicting
      SO2/NO sorption capacity using response surface and neural network models.
AB  - In this work, the application of response surface and neural network models in
      predicting and optimizing the preparation variables of RHA/CaO/CeO(2) sorbent
      towards SO(2)/NO sorption capacity was investigated. The sorbents were prepared
      according to central composite design (CCD) with four independent variables (i.e.
      hydration period, RHA/CaO ratio, CeO(2) loading and the use of RHA(raw) or
      pretreated RHA(600 degrees C) as the starting material). Among all the variables
      studied, the amount of CeO(2) loading had the largest effect. The response
      surface models developed from CCD was effective in providing a highly accurate
      prediction for SO(2) and NO sorption capacities within the range of the sorbent
      preparation variables studied. The prediction of CCD experiment was verified by
      neural network models which gave almost similar results to those determined by
      response surface models. The response surface models together with neural network
      models were then successfully used to locate and validate the optimum hydration
      process variables for maximizing the SO(2)/NO sorption capacities. Through this
      optimization process, it was found that maximum SO(2) and NO sorption capacities
      of 44.34 and 3.51 mg/g, respectively could be obtained by using RHA/CaO/CeO(2)
      sorbents prepared from RHA(raw) with hydration period of 12h, RHA/CaO ratio of
      2.33 and CeO(2) loading of 8.95%.

PMID- 20137858
TI  - Ventromedial prefrontal neurokinin 1 receptor availability is reduced in chronic
      pain.
AB  - Neurokinin 1 (NK1) receptors are involved in pain and anxiety behaviors in
      animals, but little is known about central alterations in this receptor system in
      human pain. With positron emission tomography, using a [11]-Carbon labeled NK1
      receptor antagonist, we demonstrate attenuated NK1 receptor availability in
      frontal, insular and cingulate cortex, as well as the hippocampus, amygdala and
      the periaqueductal gray area in patients with chronic pain. The reduced
      availability was most pronounced in the ventromedial prefrontal cortex (vmPFC),
      where attenuations correlated to measures of fear and avoidance of movement.
      Further, vmPFC NK1 levels also displayed opposing influences in patients as
      compared to controls on regional cerebral blood flow in the anterior cingulate.
      We conclude that the central NK1 receptor system is altered in human chronic
      pain. The results suggest that NK1 receptors in the vmPFC modulate motor
      inhibition, and contribute to fear and avoidance of movement.

PMID- 20137860
TI  - Membrane androgen receptors may mediate androgen reinforcement.
AB  - Anabolic-androgenic steroid (AAS) abuse is widespread. Moreover, AAS are
      reinforcing, as shown by self-administration in rodents. However, the receptors
      that transduce the reinforcing effects of AAS are unclear. AAS may bind to
      classical nuclear androgen receptors (ARs) or membrane receptors. We used two
      approaches to examine the role of nuclear ARs in AAS self-administration. First,
      we tested androgen self-administration in rats with the testicular feminization
      mutation (Tfm), which interferes with androgen binding. If nuclear ARs are
      essential for AAS self-administration, Tfm males should not self-administer
      androgens. Tfm males and wild-type (WT) littermates self-administered the non
      aromatizable androgen dihydrotestosterone (DHT) or vehicle
      intracerebroventricularly (ICV) at fixed-ratio (FR) schedules up to FR5. Both Tfm
      and WT rats acquired a preference for the active nose-poke during DHT self
      administration (66.4+/-9.6 responses/4 h for Tfm and 79.2+/-11.5 for WT
      responses/4 h), and nose-pokes increased as the FR requirement increased.
      Preference scores were significantly lower in rats self-administering vehicle
      (42.3+/-5.3 responses/4 h for Tfm and 19.1+/-4.0 responses/4 h for WT). We also
      tested self-administration of DHT conjugated to bovine serum albumin (BSA) at C3
      and C17, which is limited to actions at the cell surface. Hamsters were allowed
      to self-administer DHT, BSA and DHT-BSA conjugates for 15 days at FR1. The
      hamsters showed a significant preference for DHT (18.0+/-4.1 responses/4 h) or
      DHT-BSA conjugates (10.0+/-3.7 responses/4 h and 21.0+/-7.2 responses/4 h), but
      not for BSA (2.5+/-2.4 responses/4 h). Taken together, these data demonstrate
      that nuclear ARs are not required for androgen self-administration. Furthermore,
      androgen self-administration may be mediated by plasma membrane receptors.

PMID- 20137861
TI  - Vitamin A deficiency in pregnant women and respiratory morbidity in their infants
      - is there a link?

PMID- 20137862
TI  - Total body irradiation compared with BEAM: Long-term outcomes of peripheral blood
      autologous stem cell transplantation for non-Hodgkin's lymphoma.
AB  - PURPOSE: The optimal preparative regimen for non-Hodgkin's lymphoma patients
      undergoing autologous peripheral blood stem cell transplantation (PBSCT) is
      unknown. We compared a total body irradiation (TBI)-based regimen with a
      chemotherapy-alone regimen. METHODS AND MATERIALS: A retrospective cohort study
      was performed at a Canadian cancer center. The TBI regimen consisted of
      cyclophosphamide, etoposide, and TBI 12 Gy in six fractions (CY/E/TBI). The
      chemotherapy-alone regimen consisted of carmustine, etoposide, cytarabine, and
      melphalan (BEAM). We compared the acute and long-term toxicities, disease relapse
      free survival, and overall survival (OS). RESULTS: Of 73 patients, 26 received
      CY/E/TBI and 47 received BEAM. The median follow-up for the CY/E/TBI group was
      12.0 years and for the BEAM group was 7.3 years. After PBSCT, no differences in
      acute toxicity were seen between the two groups. The 5-year disease relapse-free
      survival rate was 50.0% and 50.7% in the CY/E/TBI and BEAM groups, respectively
      (p = .808). The 5-year OS rate was 53.9% and 63.8% for the CY/E/TBI and BEAM
      groups, respectivey (p = .492). The univariate analysis results indicated that
      patients with Stage IV, with chemotherapy-resistant disease, and who had received
      PBSCT before 2000 had inferior OS. A three-way categorical analysis revealed that
      transplantation before 2000, rather than the conditioning regimen, was a more
      important predictive factor of long-term outcome (p = .034). CONCLUSION: A 12-Gy
      TBI-based conditioning regimen for PBSCT for non-Hodgkin's lymphoma resulted in
      disease relapse-free survival and OS similar to that after BEAM. PBSCT before
      2000, and not the conditioning regimen, was an important predictor of long-term
      outcomes. TBI was not associated with more acute toxicity or pneumonitis. We
      found no indication that the TBI regimen was inferior or superior to BEAM.

PMID- 20137863
TI  - Behavior of lipiodol markers during image guided radiotherapy of bladder cancer.
AB  - PURPOSE: To investigate the stability of a novel type of markers used in partial
      bladder tumor irradiation and tumor deformation as indicated by the markers.
      MATERIALS AND METHODS: In 15 patients with solitary bladder cancer, lipiodol was
      injected in the bladder wall during flexible cystoscopy to identify the tumor. A
      planning CT scan was made, followed by daily cone-beam CT (CBCT) scans during
      treatment. To study the accuracy of using these markers for image guidance,
      uncertainties U1 and U2 were calculated, which were defined as the difference
      between submask registration (covering single marker) and the average of all
      submask registrations and the difference between the submask registration and the
      general mask registration (including all markers), respectively. Finally, to
      study tumor deformation, the relative movement of each marker pair was correlated
      with the relative bladder volume (RBV). RESULTS: The analyzed patients had 2.3
      marker injections on average. The lipiodol spot size was 0.72 +/- 1.1 cm(3). The
      intensity of spots in both CT and CBCT was significantly higher than the
      surrounding bladder tissue. The uncertainties U1 and U2 were comparable, and the
      uncertainties in left-right direction (0.14-0.19 cm) were smaller than those in
      cranial-caudal and anterior-posterior directions (0.19-0.32 cm). The relative
      marker movement of within-zone marker pairs was much smaller (and has less
      dependence on the RBV) than across-zones marker pairs. CONCLUSIONS: Lipiodol
      markers are a feasible method to track bladder tumor by using online CBCT. Tumor
      deformation is observed, especially for tumors that cross the defined bladder
      zones.

PMID- 20137864
TI  - Sexual function after stereotactic body radiotherapy for prostate cancer: results
      of a prospective clinical trial.
AB  - PURPOSE: To study the sexual quality of life for prostate cancer patients after
      stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Using the Expanded
      Prostate Cancer Index Composite (EPIC)-validated quality-of-life questionnaire,
      the sexual function of 32 consecutive patients who received prostate SBRT in a
      prospective Phase II clinical trial were analyzed at baseline, and at median
      times of 4, 12, 20, and 50 months after treatment. SBRT consisted of 36.25 Gy in
      five fractions of 7.25 Gy using the Cyberknife. No androgen deprivation therapy
      was given. The use of erectile dysfunction (ED) medications was monitored. A
      comprehensive literature review for radiotherapy-alone modalities based on
      patient self-reported questionnaires served as historical comparison. RESULTS:
      Median age at treatment was 67.5 years, and median follow-up was 35.5 months
      (minimum 12 months). The mean EPIC sexual domain summary score, sexual function
      score, and sexual bother score decreased by 45%, 49%, and 25% respectively at 50
      months follow-up. These differences reached clinical relevance by 20 months after
      treatment. Baseline ED rate was 38% and increased to 71% after treatment (p =
      0.024). Use of ED medications was 3% at baseline and progressed to 25%. For
      patients aged <70 years at follow-up, 60% maintained satisfactory erectile
      function after treatment compared with only 12% aged >=70 years (p = 0.008).
      Penile bulb dose was not associated with ED. CONCLUSIONS: The rates of ED after
      treatment appear comparable to those reported for other modalities of
      radiotherapy. Given the modest size of this study and the uncertainties in the
      physiology of radiotherapy-related ED, these results merit further
      investigations.

PMID- 20137865
TI  - Evaluation of tumor position and PTV margins using image guidance and respiratory
      gating.
AB  - PURPOSE: To evaluate the margins currently used to generate the planning target
      volume for lung tumors and to determine whether image-guided patient setup or
      respiratory gating is more effective in reducing uncertainties in tumor position.
      METHODS AND MATERIALS: Lung tumors in 7 patients were contoured on serial four
      dimensional computed tomography (4DCT) data sets (4-8 4DCTs/patient; 50 total)
      obtained throughout the course of treatment. Simulations were performed to
      determine the tumor position when the patient was aligned using skin marks, image
      guided setup based on vertebral bodies, fiducials implanted near the tumor, and
      the actual tumor volume under various scenarios of respiratory gating. RESULTS:
      Because of the presence of setup uncertainties, the reduction in overall margin
      needed to completely encompass the tumor was observed to be larger for imaged
      guided patient setup than for a simple respiratory-gated treatment. Without
      respiratory gating and image-guided patient setup, margins ranged from 0.9 cm to
      3.1 cm to completely encompass the tumor. These were reduced to 0.7-1.7 cm when
      image-guided patient setup was simulated and further reduced with respiratory
      gating. CONCLUSIONS: Our results indicate that if respiratory motion management
      is used, it should be used in conjunction with image-guided patient setup in
      order to reduce the overall treatment margin effectively.

PMID- 20137866
TI  - Phase I study of vandetanib with radiotherapy and temozolomide for newly
      diagnosed glioblastoma.
AB  - PURPOSE: Increasing evidence has suggested that angiogenesis inhibition might
      potentiate the effects of radiotherapy and chemotherapy in patients with
      glioblastoma (GBM). In addition, epidermal growth factor receptor inhibition
      might be of therapeutic benefit, because the epidermal growth factor receptor is
      upregulated in GBM and contributes to radiation resistance. We conducted a Phase
      I study of vandetanib, an inhibitor of vascular endothelial growth factor
      receptor 2 and epidermal growth factor receptor, in patients with newly diagnosed
      GBM combined with RT and temozolomide (TMZ). METHODS AND MATERIALS: A total of 13
      GBM patients were treated with vandetanib, radiotherapy, and concurrent and
      adjuvant TMZ, using a standard "3 + 3" dose escalation. The maximal tolerated
      dose was defined as the dose with <1 of 6 dose-limiting toxicities during the
      first 12 weeks of therapy. The eligible patients were adults with newly diagnosed
      GBM, Karnofsky performance status of >or=60, normal organ function, who were not
      taking enzyme-inducing antiepileptic drugs. RESULTS: Of the 13 patients, 6 were
      treated with vandetanib at a dose of 200mg daily. Of the 6 patients, 3 developed
      dose-limiting toxicities within the first 12 weeks, including gastrointestinal
      hemorrhage and thrombocytopenia in 1 patient, neutropenia in 1 patient, and
      diverticulitis with gastrointestinal perforation in 1 patient. The other 7
      patients were treated with 100 mg daily, with no dose-limiting toxicities
      observed, establishing this dose as the maximal tolerated dose combined with TMZ
      and RT. CONCLUSION: Vandetanib can be safely combined with RT and TMZ in GBM
      patients. A Phase II study in which patients are randomized to vandetanib 100 mg
      daily with RT and TMZ or RT and TMZ alone is underway.

PMID- 20137867
TI  - Evaluation of late adverse events in long-term wilms' tumor survivors.
AB  - PURPOSE: To evaluate the prevalence and severity of adverse events (AEs) and
      treatment-related risk factors in long-term Wilms' tumor (WT) survivors, with
      special attention to radiotherapy. METHODS AND MATERIALS: The single-center study
      cohort consisted of 185 WT survivors treated between 1966 and 1996, who survived
      at least 5 years after diagnosis. All survivors were invited to a late-effects
      clinic for medical assessment of AEs. AEs were graded for severity in a
      standardized manner. Detailed radiotherapy data enabled us to calculate the
      equivalent dose in 2 Gy fractions (EQD(2)) to compare radiation doses in a
      uniform way. Risk factors were evaluated with multivariate logistic regression
      analysis. RESULTS: Medical follow-up was complete for 98% of survivors (median
      follow-up, 18.9 years; median attained age, 22.9 years); 123 survivors had 462
      AEs, of which 392 had Grade 1 or 2 events. Radiotherapy to flank/abdomen
      increased the risk of any AE (OR, 1.08 Gy(-1) [CI, 1.04-1.13]). Furthermore,
      radiotherapy to flank/abdomen was associated with orthopedic events (OR, 1.09 Gy(
      1) [CI, 1.05-1.13]) and second tumors (OR, 1.11 Gy(-1) [CI, 1.03-1.19]). Chest
      irradiation increased the risk of pulmonary events (OR, 1.14 Gy(-1) [CI, 1.06
      1.21]). Both flank/abdominal and chest irradiation were associated with
      cardiovascular events (OR, 1.05 Gy(-1) [CI, 1.00-1.10], OR, 1.06 Gy(-1) [CI, 1.01
      1.12]) and tissue hypoplasia (OR, 1.17 Gy(-1) [CI, 1.10-1.24], OR 1.10 Gy(-1)
      [CI, 1.03-1.18]). CONCLUSION: The majority of AEs, overall as well as in
      irradiated survivors, were mild to moderate. Nevertheless, the large amount of
      AEs emphasizes the importance of follow-up programs for WT survivors.

PMID- 20137868
TI  - Preliminary results on setup precision of prone-lateral patient positioning for
      whole breast irradiation.
AB  - PURPOSE: The aim of this study was to develop a rapid and reproducible technique
      for prone positioning and to compare dose-volume indices in prone and supine
      positions. METHODS AND MATERIALS: Eighteen patients underwent computed tomography
      imaging for radiotherapy planning in prone and supine position. Experience was
      gained in the first eight patients, which lead to modifications of the Horizon
      prone breast board (Civco Medical Solutions, Orange City, Iowa, USA) and the
      patient setup technique. A unilateral breast holder (U-BH) was developed (Van de
      Velde, Schellebelle, Belgium) to retract the contralateral breast away from the
      treated breast. The technique was then applied to an additional 10 patients. The
      setup precision was evaluated using daily cone-beam CT. RESULTS: Modifications to
      the breast board were made to secure a prone-lateral rather then a pure prone
      position. We evolved from a classical setup using laser marks on the patients'
      body to a direct breast setup using marks on the breast only. The setup precision
      of the direct positioning procedure with the modified breast board and the U-BH
      is comparable to supine setup data in the literature. Dose-volume indices for
      heart and lung show significantly better results for prone than for supine
      position, and dose homogeneity within the treated breast did not differ according
      to the treatment position. CONCLUSIONS: The setup precision of our prone-lateral
      positioning technique is comparable to supine data in literature. Our data show
      the advantage of prone radiotherapy to spare the lung and heart. Further research
      is necessary to reduce the duration of prone setup.

PMID- 20137869
TI  - Alcohol pharmacokinetics, decision making and folk wisdom: a reply to Moxnes and
      Jensen (2009).
AB  - Moxnes and Jensen (2009) present a study of decision making under conditions of
      uncertainty using a computerised simulation of alcohol pharmacokinetics. In their
      article, they conclude that their findings challenge the 'folk wisdom' that
      advises against drinking on an empty stomach. We contend that this is a
      problematic conclusion for three reasons: (1) the study and findings presented in
      their paper are simply not sufficient to allow one to, even tentatively, draw
      such a conclusion; (2) the conclusion is contrary to basic pharmacological
      knowledge concerning alcohol absorption, metabolism and the implications for peak
      blood alcohol concentration; and (3) the implications for understanding the
      process of decision making while alcohol intoxicated are not considered in the
      study. The Moxnes and Jensen (2009) study did not involve alcohol administration
      and is therefore an examination of decision making in situations of uncertainty
      rather than a specific exploration of drinking-related decision making. Recent
      formulations of the effects of alcohol on cognitive processing would lead to
      different conclusions than those presented by Moxnes and Jensen (2009). We
      conclude by suggesting our understanding of the implications of the study.

PMID- 20137870
TI  - Sex-preselected buffalo (Bubalus bubalis) calves derived from artificial
      insemination with sexed sperm.
AB  - Flow cytometry sorting of X- and Y-chromosome bearing sperm has been emerging as
      a promising technology to alter the sex ratio in progenies of mammals in the
      recent years. The objective of this study was to evaluate the efficiency of AI by
      using the sexed sperm to produce sex-preselected calves in buffalo species. A
      total of 43 buffalo cows were inseminated with X-sorted sperm, 30 of which were
      confirmed pregnant 3 mo following AI. In terms of conception rate, significant
      difference was observed between AI with sexed sperm derived from different bulls
      (P<0.05), but not between sexed and non-sexed sperm (P>0.05), nor between heifers
      and parous buffalo cows (P>0.05). A total of 29 sex-preselected calves, 24
      females and 5 males, developed to term and were viable on delivery. Results of
      this study indicate the feasibility of the application of the sexing technology
      to accelerate the genetic improvement in swamp buffalo.

PMID- 20137871
TI  - Assessment of self-esteem in mid-aged women.
AB  - OBJECTIVE: To assess self-esteem and affecting factors in a middle-aged
      Ecuadorian female population using the Rosenberg Self-Esteem Scale (RSES). STUDY
      DESIGN: This was a cross-sectional study in which 149 women (40-59 years) were
      requested to fill out the RSES and a general socio-demographic form containing
      personal and partner data. RESULTS: Mean age of sample was 47.6+/-5.5 years, a
      67.8% had less than 12 years of schooling and 33.6% were postmenopausal. At the
      moment of the survey 2.7% were on hormone therapy, and 2% were taking
      psychotropic drugs. Mean total RSES score was 26.6+/-3.1 (median 26, range 17
      35). A 35.6% and 18.1% of women respectively presented total RSES scores below 26
      (median) and 25 (25th percentile) suggesting lower self-esteem. Total scores did
      not differ when comparing older age, menopausal phases or time since the
      menopause. Logistic regression analysis determined that women with lower parity
      and an unhealthy partner were related to lower total RSES scores (below the 25th
      percentile) suggesting lower self-esteem. CONCLUSIONS: In this mid-aged series
      lower self-esteem was not related to the aging process per se yet to socio
      demographic female/male aspects. More research is needed in this regard that
      incorporates other sociological aspects.

PMID- 20137872
TI  - A probability-based sampling approach for the analysis of drug seizures composed
      of multiple containers of either cocaine, heroin, or Cannabis.
AB  - A probability-based analytical sampling approach for seized containers of
      cocaine, Cannabis, or heroin, to answer questions of both content weight and
      identity, is described. It utilizes the Student's t distribution, and, because of
      the lack of normality in studied populations, the power of the Central Limit
      Theorem with samples of size 20 to calculate the mean net weights of multiple
      item drug seizures. Populations studied ranged between 50 and 1200 units.
      Identity determination is based on chemical testing and sampling using the
      hypergeometric distribution fit to a program macro - created by the European
      Network of Forensic Science Institutes (ENFSI) Drugs Working Group. Formal random
      item selection is effected through use of an Excel-generated list of random
      numbers. Included, because of their impact on actual practice, are discussions of
      admissibility, sufficiency of proof, method validation, and harmony with the
      guidelines of international standardizing bodies.

PMID- 20137873
TI  - Widespread pulmonary granulomatosis following long time intravenous drug abuse--a
      case report.
AB  - Foreign body granulomas in the lungs following acute singular or long time
      intravenous drug abuse are frequent findings during microscopic investigation of
      the lungs. Most cases present single granulomas. Cases with multiple foreign body
      granulomas, already palpable during autopsy and leading to pulmonary
      granulomatosis with multiple granulomas are less frequent. We report the case of
      a 32-year old man, dying suddenly and unexpectedly after a well-known history of
      drug abuse for more than a decade. The granulomas are caused by foreign particle
      embolization immediately after intravenous injection of not only the drug itself
      but also of adulterants, e.g. cotton fibers, potato starch or microcrystalline
      cellulose. At the end, a reduction in the size of the pulmonary bed had occurred
      followed by pulmonary hypertension. For the first time, lung dust in such a case
      was characterised by energy dispersive X-ray (EDX).

PMID- 20137874
TI  - Diffusion tensor imaging with cerebrospinal fluid suppression and signal-to-noise
      preservation using acquisition combining fluid-attenuated inversion recovery and
      conventional imaging: comparison of fiber tracking.
AB  - OBJECTIVE: To propose an acquisition scheme suitable for fiber tractography
      without cerebrospinal fluid contamination while retaining high signal-to-noise
      ratio. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) data at b=0 and 1000
      s/mm(2) were acquired using conventional spin-echo echo-planar imaging
      (TR/TE=4000/69, NEX=4, scan time 2:14) plus one additional fluid-attenuated
      inversion recovery (FLAIR) b=0 set obtained at TI=2200, TR=6000, and NEX=6 (scan
      time 1:36). The FLAIR images were intensity-adjusted to match the conventional
      b=0 images according to the white matter signals. Five healthy adults were
      scanned, with tractography performed from conventional b=1000 and FLAIR b=0
      images using the EZ-tracing algorithm. Total traced volumes were statistically
      compared among conventional DTI, FLAIR DTI, and the "combined DTI" methods at
      three different slice thicknesses. The fiber consistency index was derived for
      five repeated scans to assess possible false tracts. RESULTS: Whole-brain traced
      volumes from FLAIR DTI and combined DTI were 9.7% (p<0.001) and 17.0% (p<0.0001)
      greater than from conventional DTI, respectively (paired Student t-test). Fiber
      consistency was similar for all three acquisition techniques (p>0.2), suggesting
      insignificant difference in false tracking. Compared with conventional DTI, the
      increase in total traced volume for FLAIR DTI diminished with decreasing slice
      thickness, whereas the tractography advantage for combined DTI became
      increasingly prominent at thinner slices. CONCLUSIONS: The combined DTI technique
      is capable of improving tractography with higher signal-to-noise ratio at shorter
      scan time than FLAIR DTI. Its superiority at thin-slice acquisitions makes it
      particularly suitable for high-resolution clinical applications.

PMID- 20137875
TI  - Dislocation and spontaneous reduction of the femoral implant against the femoral
      neck in an infected metal on metal hip resurfacing with complex collection.
AB  - Metal on metal resurfacing hip implants are known to have complications unique to
      this type of implant. The case presented adds a further previously not described
      complication, the dislocation and spontaneous reduction of the pin of the femoral
      component against the femoral neck. The radiographic and CT findings are
      demonstrated. The dislocation was aided by bone loss due to an infection with a
      large periarticular collection. Periarticular collections in hip resurfacings are
      often due to a hypersensitivity type reaction to metal debris. However in the
      case presented it was due to infection. MRI was not able to discern the infection
      from a sterile collection. CT demonstrated bone loss and periosteal reaction
      suggestive of infection. In addition calcification of the pseudocapsule was seen,
      this is not a recognized feature of sterile collections.

PMID- 20137876
TI  - Urine sensor device for fluoroscopy time reduction in pediatric voiding
      cystourethrography.
AB  - PURPOSE: We evaluated the feasibility of a using urine sensor for voiding
      cystourethrography (VCUG) and its implications for fluoroscopy time reduction.
      MATERIALS AND METHODS: Institutional Review Board approved the study protocol.
      Study population included children less than 5 years old referred to our
      institution for VCUG. Patients with known vesicoureteral reflux or any pacing
      device were excluded from the study. The urine sensor consists of an electrode
      that senses the fluid, an electrical circuit and an indicator to provide visual
      signal. The urine sensor electrode was placed on the medial thigh in the
      proximity of the catheter close to the urethral opening, but without direct
      contact to it. A standard VCUG examination was performed with retrograde filling
      of the urinary bladder. Once the bladder was full, fluoroscopy of the voiding
      stage was initiated when the indicator blinked. Peak kV and fluoroscopy time were
      recorded. RESULTS: Seven patients underwent VCUG with urine sensor and 22
      patients without urine sensor. The urine sensor provided a reliable indication of
      voiding onset. The fluoroscopy time was significantly shorter with urine sensor
      use (1.99 min) than without urine sensor use (4.33 min) (p=0.001). In patients
      with normal VCUG, fluoroscopy time was also significantly shorter with urine
      sensor use (2.13 min) than without urine sensor use (4.39 min) (p<0.001).
      CONCLUSION: VCUG studies with the help of the urine sensor are feasible and its
      use may result in significant reduction in fluoroscopy time.

PMID- 20137877
TI  - Study on the radical scavengers in the traditional Chinese medicine formula
      shengmai san by HPLC-DAD coupled with chemiluminescence (CL) and ESI-MS/MS.
AB  - Shengmai San (SMS) has been used for the treatment of cardiovascular disease in
      Asia for long-time. It has been reported that SMS can protect against oxidative
      stress and tune immune response in patients. In this paper, a high performance
      liquid chromatography-diode array detection-chemiluminescence (HPLC-DAD-CL)
      method for on-line detection was successfully applied to screen antioxidants in
      complex SMS extracts. The H(2)O(2) scavenging activity of every fraction of SMS
      extracts was measured to evaluate each contribution to the total anti-oxidative
      activities of the prescription, followed by structures identification of the main
      active components by LC/MS/MS. HPLC-DAD-CL method was also applied for comparing
      the scavenging rates of main active components between the individual herbs and
      SMS. Interestingly, we found that the scavenging activities of main components
      detected in the individual herbs were different from those in SMS. The
      experimental data indicated that drug interactions during decocting process could
      result in the changes of the antioxidants' solubility. This study demonstrated
      that HPLC-DAD-CL on-line assay was a useful technique for rapidly screening and
      identifying bioactive components from complex multi-herbal prescription.

PMID- 20137878
TI  - A step forward in the evaluation of transcatheter aortic valve implantation.

PMID- 20137879
TI  - Endovascular aortic repair versus open surgical repair for descending thoracic
      aortic disease a systematic review and meta-analysis of comparative studies.
AB  - OBJECTIVES: The purpose of this study was to determine whether thoracic
      endovascular aortic repair (TEVAR) reduces death and morbidity compared with open
      surgical repair for descending thoracic aortic disease. BACKGROUND: The role of
      TEVAR versus open surgery remains unclear. Metaregression can be used to
      maximally inform adoption of new technologies by utilizing evidence from existing
      trials. METHODS: Data from comparative studies of TEVAR versus open repair of the
      descending aorta were combined through meta-analysis. Metaregression was
      performed to account for baseline risk factor imbalances, study design, and
      thoracic pathology. Due to significant heterogeneity, registry data were analyzed
      separately from comparative studies. RESULTS: Forty-two nonrandomized studies
      involving 5,888 patients were included (38 comparative studies, 4 registries).
      Patient characteristics were balanced except for age, as TEVAR patients were
      usually older than open surgery patients (p = 0.001). Registry data suggested
      overall perioperative complications were reduced. In comparative studies, all
      cause mortality at 30 days (odds ratio [OR]: 0.44, 95% confidence interval [CI]:
      0.33 to 0.59) and paraplegia (OR: 0.42, 95% CI: 0.28 to 0.63) were reduced for
      TEVAR versus open surgery. In addition, cardiac complications, transfusions,
      reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were
      reduced. There was no significant difference in stroke, myocardial infarction,
      aortic reintervention, and mortality beyond 1 year. Metaregression to adjust for
      age imbalance, study design, and pathology did not materially change the results.
      CONCLUSIONS: Current data from nonrandomized studies suggest that TEVAR may
      reduce early death, paraplegia, renal insufficiency, transfusions, reoperation
      for bleeding, cardiac complications, pneumonia, and length of stay compared with
      open surgery. Sustained benefits on survival have not been proven.

PMID- 20137880
TI  - [Report of the 16th meeting of the anesthesia club in ORL (Carorl)].

PMID- 20137881
TI  - Relationship between N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and
      cardiac cycle efficiency in cardiac surgery.
AB  - N-terminal pro-B-type natriuretic peptide (Nt-proBNP) is a peptide released from
      myocardium in response to ventricular wall stress and dysfunction. Nt-proBNP
      plasma levels are elevated in a variety of cardiovascular disorders and are
      largely used for diagnosis and treatment of cardiac diseases. The cardiac cycle
      efficiency (CCE) is a haemodynamic variable that represents the left ventricle
      wall stress and the heart's effort to maintain an adequate blood flow to tissues.
      We investigated the relationship between Nt-proBNP and CCE values in patients
      undergoing cardiac surgery. Twenty-five patients undergoing aortic valve
      replacement were studied. Plasma Nt-proBNP concentrations were performed by
      electroluminescence immunoassay before starting surgery (t0), at the end of
      extracorporeal circulation (t1) and 3 hours after surgery (t2). CCE measurements
      were acquired at the same intervals and correlations with Nt-proBNP levels were
      calculated. Nt-proBNP plasma concentration was 1430 +/- 341 pg/ml at t0, peaked
      significantly at t1 (2129 +/- 561 pg/ml, p<0.001) and moderately decreased at t2
      (1924 +/- 477 pg/ml, p<0.05). A direct correlation between Nt-proBNP measured at
      t0 and t1 was found (r=0.91, p<0.001). Overall, a negative correlation between
      CCE and proBNP values was found (r=-0.89, p<0.01). Correlations between CCE and
      Nt-proBNP were -0.91, -0.83 and -0.88, at t0, t1 and t2, respectively (p<0.01).
      Nt-proBNP levels reflect the severity of left ventricle dysfunction in patients
      undergoing cardiac surgery. CCE correlated well with serum Nt-proBNP levels and
      seems to be a useful variable to monitor the left ventricular stress and recovery
      during the various phases of surgery.

PMID- 20137882
TI  - A common polymorphism in CD40 Kozak sequence (-1C/T) is associated with acute
      coronary syndrome.
AB  - OBJECTIVE: Evidence suggests the CD40-CD40L pathway as a key process in the
      development, progression, and outcome of acute coronary syndrome (ACS). We
      hypothesized that the -1C/T polymorphism of the CD40 gene would be associated
      with ACS and influence the CD40 expression. METHODS: The genotype distribution
      and allele frequency of CD40-1C/T polymorphism in 248 ACS patients and 206
      controls were analyzed by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). Monocytes from 90 healthy volunteers were incubated with
      IFN-gamma. CD40 expression was detected by flow cytometry. RESULT: Patients with
      ACS showed a significant increase of CD40 expression compared with controls
      (P<0.001). The frequency of the CC genotype in the ACS group was significantly
      higher than that of the controls (P<0.001). Frequency of the C allele was higher
      among ACS patients compared with controls (P<0.001). Case control association
      analysis of the CD40 -1C/T SNP showed an association between the C allele and ACS
      (OR=1.991, 95%CI: 1.526 approximately 2.596, P<0.001). -1C/C carriers presented
      significantly higher CD40 expression levels than -1C/T and -1T/T subjects, both
      in ACS group and controls (P<0.001). When stimulated by IFN-gamma, CD40
      expression levels on monocytes in individuals with CC, CT and TT genotypes were
      increased by 9.16, 3.83 and 1.53 fold, respectively, compared with the levels
      absent with IFN-gamma. CONCLUSIONS: These results suggest that the -1C allele of
      the CD40 (-1C/T) gene polymorphism is a genetic factor that may determine an
      individual's susceptibility by ACS in Chinese. The CD40 -1C/T polymorphism is a
      novel regulator of CD40 expression.

PMID- 20137883
TI  - Sensitivity of a direct computer-aided detection system in full-field digital
      mammography for detection of microcalcifications not associated with mass or
      architectural distortion.
AB  - PURPOSE: The purpose of this study was to evaluate the sensitivity of a direct
      computer-aided detection (CAD) system (d-CAD) in full-field digital mammography
      (FFDM) for the detection of microcalcifications not associated with mass or
      architectural distortion. MATERIALS AND METHODS: A database search of 1063
      consecutive stereotactic core biopsies performed between 2002 and 2005 identified
      196 patients with Breast Imaging-Reporting and Data System (BI-RADS) 4 and 5
      microcalcifications not associated with mass or distortion detected exclusively
      by bilateral FFDM. A commercially available CAD system (Second Look, version 7.2)
      was retrospectively applied to the craniocaudal and mediolateral oblique views in
      these patients (mean age, 59 years; range, 35-84 years). Breast density, location
      and mammographic size of the lesion, distribution, and tumour histology were
      recorded and analysed by using chi(2), Fisher exact, or McNemar tests, when
      applicable. RESULTS: When using d-CAD, 71 of 74 malignant microcalcification
      cases (96%) and 101 of 122 benign microcalcifications (83%) were identified.
      There was a significant difference (P < .05) between CAD sensitivity on the
      craniocaudal view, 91% (68 of 75), vs CAD sensitivity on the mediolateral oblique
      view, 80% (60 of 75). The d-CAD sensitivity for dense breast tissue (American
      College of Radiology [ACR] density 3 and 4) was higher (97%) than d-CAD
      sensitivity (95%) for nondense tissue (ACR density 1 and 2), but the difference
      was not statically significant. All 28 malignant calcifications larger than 10 mm
      were detected by CAD, whereas the sensitivity for lesions small than or equal to
      10 mm was 94%. CONCLUSIONS: D-CAD had a high sensitivity in the depiction of
      asymptomatic breast cancers, which were seen as microcalcifications on FFDM
      screening, with a sensitivity of d-CAD on the craniocaudal view being
      significantly better. All malignant microcalcifications larger than 10 mm were
      detected by d-CAD.

PMID- 20137884
TI  - Puck to pubalgia: imaging of groin pain in professional hockey players.

PMID- 20137885
TI  - Identification of local recurrence and radiofibrosis by computed tomography
      perfusion on nasopharyngeal carcinoma after radiotherapy.
AB  - PURPOSE: The aim of this study was to investigate the role of perfusion computed
      tomography (CT) for identification of local recurrence (LR) and radiofibrosis
      (RF) in patients with nasopharyngeal carcinoma after radiotherapy. METHODS: Forty
      eight prospective patients were recruited for this study. NPC diagnosis was
      confirmed by pathologic biopsy examination. Immunohistochemistry staining was
      used on biopsy specimens, and microvessel density was calculated by microscopy.
      Perfusion CT was performed on both the LR group (n = 31) and the RF group (n =
      17) after intravenous injection of contrast medium. Time-density curve, blood
      flow, blood volume, and mean transit time, as well as permeability surface area
      product, were analyzed as perfusion CT parameters. The microvessel density was
      compared between both the LR and RF groups. RESULTS: There is a significant
      difference between the LR and RF groups in microvessel density, the time density
      curve, blood flow blood volume, mean transit time, and the permeability surface
      area product (P < .01). CONCLUSIONS: The results demonstrate that perfusion CT is
      a reliable and accurate method to identify LR and RF after radiotherapy in
      patients with nasopharyngeal carcinoma.

PMID- 20137887
TI  - Polyethylene subluxation: a radiographic sign of locking mechanism failure after
      modular total knee arthroplasty.
AB  - Tibial insert locking mechanisms are intended to limit interface motion and
      "backside" wear in modular total knee arthroplasty (TKA). Nevertheless, anterior
      polyethylene subluxation is occasionally apparent on lateral radiographs after
      TKA, suggesting locking mechanism failure. We retrospectively identified 10
      modular posterior-stabilized implants of a single design that were found to have
      failure of the locking mechanism at the time of revision surgery for osteolysis.
      Operative reports were reviewed for the presence of backside wear, and
      preoperative radiographs were inspected for polyethylene subluxation. All 10
      implants demonstrated significant backside wear. Nine had anterior polyethylene
      subluxation evident on preoperative radiographs. Anterior polyethylene
      subluxation on the lateral radiograph is a subtle sign of failure of the locking
      mechanism in this modular posterior-stabilized TKA.

PMID- 20137888
TI  - Novel endovascular techniques for repair of traumatic bilateral axillary artery
      disruption with long-term follow-up.
AB  - We describe a case of innovative endovascular techniques to repair traumatic
      bilateral axillary artery disruption. A 36-year-old male construction worker fell
      eight stories from a scaffold and sustained bilateral axillary artery injuries.
      The injuries between the brachial and axillary arteries were bridged using long
      bare self-expanding stents (Zilver). To the best of our knowledge, this is a
      novel case report from a level-one trauma center where endovascular techniques
      were employed to repair bilateral axillary arteries with long-term follow-up.

PMID- 20137889
TI  - Acoustic analysis of voice in Huntington's disease patients.
AB  - BACKGROUND/OBJECTIVES: Alterations of voice and speech are frequently observed in
      Huntington's disease (HD). The aim of this study was to assess the degree of
      voice and speech abnormalities in a group of patients with HD and to analyze
      possible correlations with degree of disease severity. PATIENTS/METHODS: An
      observational study was carried out on diagnosed cases and controls. The voices
      of 20 patients were analyzed and compared with an age- and sex-matched control
      group. Variables analyzed included subjective voice exploration, analysis of
      aerodynamic efficiency, acoustic analysis measures, and laryngeal examination
      descriptions. Results obtained were correlated with degree of disease severity.
      RESULTS: Changes in the Voice Handicap Index and clinical characteristics of the
      voice were observed. Maximum phonation time was reduced. Acoustic analysis
      revealed changes that were analyzed. Uncontrolled adduction-abduction movements
      were observed by laryngeal examination. All results showed a positive correlation
      with degree of disease severity assessed by the Unified Huntington's Disease
      Rating Scale. CONCLUSIONS: HD causes alterations in subjective voice features,
      aerodynamic and acoustic analysis measures that are correlated with disease
      severity.

PMID- 20137890
TI  - Review of the impact of voice training on the vocal quality of professional voice
      users: implications for vocal health and recommendations for further research.
AB  - OBJECTIVE: To review the current published available research into the impact of
      voice training on the vocal quality of professional voice users, to provide
      implications for vocal health and recommendations for further research. DESIGN:
      Literature review with a systematic approach. METHODS: A systematic search of the
      literature was conducted using electronic databases and the following defined
      search terms: occupational voice or occupational dysphonia or voice and
      occupational safety and health. To obtain the comprehensive relevant literature,
      no studies were excluded on the basis of study design. In total, 10 studies that
      investigated the impact of a voice training intervention on the vocal quality of
      professional voice users as a potential prevention strategy for voice disorders
      were selected for this review. RESULTS: The 10 studies ranged in design from
      observational to randomized controlled trials with mainly small sample sizes (N =
      11-60). Nine studies showed that voice training significantly (P < 0.05) improved
      at least one voice-related measurement from the several investigated from
      baseline. Five studies reported that voice training significantly (P < 0.05)
      improved at least one measurement compared with no training. CONCLUSIONS:
      Findings indicate that there is no conclusive evidence that voice training
      improves the vocal effectiveness of professional voice users, as a result of a
      range of methodological limitations of the included studies. However, some
      studies did show that voice training significantly improved the knowledge,
      awareness, and quality of voice. Therefore, there is a need for robust research
      to empirically confirm this, with implications for vocal health, and occupational
      safety and health policies.

PMID- 20137891
TI  - Interarytenoid muscle botox injection for treatment of adductor spasmodic
      dysphonia with vocal tremor.
AB  - OBJECTIVES/HYPOTHESIS: Up to one-third of patients presenting with adductor
      spasmodic dysphonia will have an associated vocal tremor. These patients may not
      respond fully to treatment using thyroarytenoid (TA) muscle botulinum toxin
      (Botox) injection. Treatment failures are attributed to the involvement of
      multiple muscle groups in the tremor. This study evaluates the results of
      combined interarytenoid (IA) and TA muscle Botox injection in a group of 27
      patients with adductor spasmodic dysphonia and vocal tremor and in four patients
      with severe vocal tremor alone. STUDY DESIGN: Patient-satisfaction data were
      reviewed retrospectively. Pre- and postinjection acoustic data were collected
      prospectively. METHODS: Acoustic measures of fundamental frequency and cycle-by
      cycle variability in frequency (jitter) and intensity (shimmer) were obtained
      from 15 patients' sustained vowel productions. Measures were collected after TA
      muscle injection, alone, and after combined TA and IA (TA+IA) muscle injections.
      In addition, two experienced voice clinicians blindly assessed tremor severity
      from recordings made for each patient in the two conditions. Patients were also
      queried regarding their satisfaction with the results of the injections and
      whether they desired to continue receiving TA+IA treatment. RESULTS: Significant
      improvement in all acoustic measures except for % jitter was observed after the
      TA+IA muscle injections. Listeners identified voice samples after TA+IA muscle
      injections as demonstrating less tremor in 73% of the paired comparisons. Sixty
      seven percent of the patients with spasmodic dysphonia and vocal tremor wished to
      continue to receive IA muscle injections. Only one patient with severe vocal
      tremor wished to continue with injections. CONCLUSIONS: The addition of an IA
      muscle Botox injection to the treatment of patients with a combination adductor
      spasmodic dysphonia and vocal tremor may improve voice outcomes.

PMID- 20137892
TI  - Discrimination between pathological and normal voices using GMM-SVM approach.
AB  - Acoustic features of vocal tract function are used widely in the study of
      pathological voices detection. Classification of normal and pathological voices
      by acoustic parameters is a useful way to diagnose voice diseases. In this
      aspect, mel-frequency cepstral coefficients are proved to be effective with
      traditional classifiers such as Gaussian Mixture Model (GMM). However, the
      accuracy of the classification method can be further improved. In this article, a
      Gaussian mixture model supervector kernel-support vector machine (GMM-SVM)
      classifier is compared with GMM classifier for the detection of voice pathology.
      We found that a sustain vowel phonation can be classified as normal or
      pathological with an accuracy of 96.1%. Voice recordings are selected from the
      Kay database to carry out the experiments. Experimental results show that equal
      error rates decrease from 8.0% for GMM to 4.6% for GMM-SVM.

PMID- 20137893
TI  - Vocal fold elasticity in the pig, sheep, and cow larynges.
AB  - Elastic characteristics of the pig, sheep, and cow vocal folds were investigated
      through a series of in vitro experiments. Sample strips of the vocal-fold tissue
      were dissected from pig, sheep, and cow vocal folds and mounted inside a saline
      filled ergometer chamber that was maintained at 37 degrees C +/- 1 degrees C.
      Sinusoidal elongation was applied on the samples to obtain the passive force
      measurements. Force and elongation data from the samples were recorded
      electronically with a dual-servo system (ergometer). Stress-Strain data were
      compared to characterize the interspecies differences in the elastic properties
      of vocal folds. Pig vocal folds exhibited the most nonlinear stress-strain
      relationship, indicating the presence of a high level of collagen fibers. Cow
      vocal folds had the highest Young's modulus, but the tissue displayed a nearly
      linear stress-strain profile. Previous studies of phonation in these three
      species have indicated that pig larynges have the highest range of phonation
      frequencies, making them a good candidate for animal studies. The current study
      provides quantitative data for the elastic properties of the oscillating
      laryngeal tissue in these species and indicates that nonlinear behavior of these
      tissues may lead to wider oscillation ranges.

PMID- 20137894
TI  - The effect of initiating oral contraceptive use on voice: a case study.
AB  - OBJECTIVE: To examine the effects of initiating oral contraceptive (OC) use on
      spectrally based acoustic measures. STUDY DESIGN: Case history. METHODS: A 23
      year-old female volunteered to participate in the study. Voice recordings were
      obtained during eight consecutive menstrual cycles: two cycles before the onset
      of OC use and six cycles after the initiation of OC use. Recordings consisted of
      three trials of the sustained vowel /ae/ and were obtained during the follicular
      phase (preovulation, days 9-11) and luteal phase (premenstruation, days 20-22) of
      each cycle. Measurements obtained included the following: (1) H1-H2, the ratio of
      the amplitude of the first harmonic to the amplitude of the second harmonic,
      which correlates to closed quotient duration; (2) H1-A1, the ratio of the
      amplitude of the first harmonic to the amplitude of the first formant, which
      correlates to glottal width; and (3) H1-A3, the ratio of the first harmonic to
      the amplitude of the third formant, which correlates to the abruptness of vocal
      fold closure. In addition, acoustic measures of voice perturbation, jitter,
      shimmer, and noise-to-harmonic ratio were measured. RESULTS: The participant
      exhibited changes in glottal characteristics in conjunction with initiation of OC
      use. Both the H1-H2 and H1-A1 differences changed with OC use relative to
      menstrual cycle phase. These two measures have been correlated with the glottal
      measures of closed quotient and glottal width, respectively. However, there was
      no significant change in the H1-A3 difference, indicating no effect of OC use on
      the speed of vocal fold closure. CONCLUSIONS: The results of this study indicate
      that the onset of OC use can result in vocal changes as noted by different
      patterns of glottal adjustment across menstrual cycle phases.

PMID- 20137895
TI  - Qualitative characterization of elastic fiber distribution in the mouse vocal
      fold: further development of an animal model.
AB  - The purpose of this study was to identify the presence and characteristics of the
      distribution patterns of elastic fibers in a 15-week-old C57BL/6J mouse vocal
      fold, to confirm the presence and distribution of collagen fibers, and to
      describe potential gender differences in staining patterns, with the aim of
      further developing the mouse model for use in translational research of vocal
      fold physiological mechanisms. The vocal folds from 12 mice, divided equally into
      gender categories, were stained for elastic fibers and collagen fibers using
      conventional staining methods. Qualitative (subjective) visual analyses were
      performed by identifying the staining density of elastic and collagen fibers in
      the superficial half and deep half of the vocal fold lamina propria. Analyses
      revealed the presence of elastic fibers in both male and female vocal folds,
      although patterns of staining density were heavy in the deep half of the lamina
      propria, a location that is deeper than the greatest concentrations of elastic
      fibers in human vocal folds. Collagen fibers were also present in locations
      similar to those within human vocal folds, consistent with previously published
      data. The results of this study support the use of the mouse model in
      translational and basic science research, and this model may be especially useful
      for research aimed at furthering our knowledge of genetic influences on vocal
      fold structural development and function.

PMID- 20137896
TI  - Mitochondrial HMG-CoA synthase partially contributes to antioxidant protection in
      the kidney of stroke-prone spontaneously hypertensive rats.
AB  - OBJECTIVE: Increased oxidative stress plays an important role in cardiovascular
      diseases including hypertension and stroke. Evidence has indicated that ketone
      bodies could exert antioxidative effects. We explored the role of renal
      mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2) expression,
      a key control site of ketogenesis, in stroke-prone spontaneously hypertensive
      rats (SHRSPs) and their ancestral hypertensive but stroke-resistant spontaneously
      hypertensive rats (SHRs). METHODS: Two groups of SHRSPs were fed a standard chow
      or standard chow supplemented with clofibrate (an agonist of HMGCS2 promoter),
      respectively, and SHRs fed with a standard chow were used as controls. The renal
      levels of HMGCS2, Akt, and phosphorylated protein kinase B (Akt) were measured by
      western blotting. Malondialdehyde, catalase, superoxide dismutase, and
      glutathione peroxidase were detected by assay kits. RESULTS: Compared with SHRs,
      lower HMGCS2 protein expression, enhanced phosphorylated Akt signal, higher
      malondialdehyde levels, and higher catalase activity were observed in kidney
      tissues in SHRSPs (P < 0.05). No differences in superoxide dismutase and
      glutathione peroxidase activities were observed between SHRSPs and SHRs.
      Clofibrate treatment significantly upregulated renal HMGCS2 expressions,
      inhibited phosphorylation of Akt, and decreased malondialdehyde levels and
      catalase activities in SHRSP kidney tissues (P < 0.05). CONCLUSION: These results
      demonstrated the difference in HMGCS2 expression and oxidative stress in kidney
      tissues between SHRSPs and their SHR controls. The enhanced oxidative stress was
      partly due to the lower HMGCS2 expression regulated possibly by the Akt signaling
      pathway.

PMID- 20137898
TI  - Follow up study of dermal hyaluronic acid injection by high frequency ultrasound
      and magnetic resonance imaging.

PMID- 20137899
TI  - Complete nucleotide sequence of the fosfomycin resistance transposon Tn2921.

PMID- 20137900
TI  - Activity of tigecycline against methicillin-resistant Staphylococcus aureus
      (MRSA) from respiratory tract sources.

PMID- 20137901
TI  - Immunodiagnosis of Chagas disease: Synthesis of three latex-protein complexes
      containing different antigens of Trypanosoma cruzi.
AB  - This article describes the physical adsorption and the chemical coupling of 3
      antigenic proteins of Trypanosoma cruzi onto polystyrene (PS) based latexes to be
      used as novel immunodiagnosis reagents for detecting the Chagas disease. The
      coupled proteins were a homogenate of T. cruzi, or a recombinant protein (either
      Ag36 or CP1). With the homogenate, between 30 and 60% of the total-linked protein
      was chemically coupled, showing a small dependence with the pH. For Ag36 and CP1,
      around 90% of the total-linked protein was chemically coupled, with a maximum
      coupling at pH 5 (i.e., close to the isoelectric point). The chemical coupling of
      CP1 was less affected by the pH than the coupling of Ag36.

PMID- 20137902
TI  - Layer-by-layer assembly of polysaccharide-based nanostructured surfaces
      containing polyelectrolyte complex nanoparticles.
AB  - Nanoscale chemical and topographical features have been demonstrated to influence
      a variety of significant responses of mammalian cells to biomaterials surfaces.
      Thus, an important goal for biomaterials scientists is the ability to engineer
      the nanoscale surface features of biologically active materials. The goal of the
      current work is to demonstrate that polyelectrolyte complex nanoparticles (PCNs)
      in polyelectrolyte multilayers (PEMs) can be combined to create surfaces with
      controlled nanoscale surface topography and nanoscale presentation of surface
      chemistry. The polysaccharides used in this work are the biomedically relevant
      chitosan, heparin, and hyaluronan. Nanostructured surface coatings were
      characterized on both modified gold substrates and tissue-culture polystyrene
      surfaces. PCNs were adsorbed to oppositely charged PEMs, and were also embedded
      within PEMs. The construction of the surface coatings was characterized by quartz
      crystal microbalance with dissipation (QCM-D). The surface morphology was
      characterized by scanning electron microscopy (SEM) and atomic force microscopy
      (AFM). The chemistry of the coatings was confirmed by both X-ray photoelectron
      spectroscopy (XPS) and polarization modulation infra-red reflection absorption
      spectroscopy (PM-IRRAS). Morphologically, we found that PCNs were colloidally
      stable and homogeneously distributed when adsorbed on or in the PEMs. Chemical
      analysis confirms that the PCNs adsorbed to PEMs significantly altered the
      surface chemistry, indicating significant surface coverage. Furthermore, the
      position of the PCNs normal to the surface can be adjusted by adding PEMs on top
      of adsorbed PCNs. Thus, PCNs can be used to introduce discrete nanoscale surface
      topographical features and varying surface chemistry into PEM surface coatings in
      a controlled way.

PMID- 20137903
TI  - [Teenagers and age of first drinking: A disturbing precocity?].
AB  - Age of first drink in France and Western countries is early. National and
      international surveys confirm this early onset. Drunkenness, which is the most
      obvious drinking outcome, seems to rise amongst young adolescents. Consequences
      of this precocity are considerable. At short-term, drunk teenagers are more
      frequently victims of accidents. In addition, they are more vulnerable to sexual
      abuses, as victims but also as perpetrators. At medium- and long-terms, the early
      development of alcohol use is linked to higher levels of later drinking
      dependence. Three explanatory ways for this precocity are developed: family's
      influence, role of advertising and media, and role of peers. When alcohol meets
      adolescence, it is sometimes a real storm. Prevention is uneasy because of the
      very commonplace of alcohol at home. It can concern family level or society
      level. As for tobacco, society intervention is needed to delay age of first drink
      and limit teenager alcohol use but this should not involved adolescents
      condemnation.

PMID- 20137904
TI  - Inhibition of cyclophosphamide-induced oxidative stress in rat brain by polar and
      non-polar extracts of Annatto (Bixa orellana) seeds.
AB  - Annatto (Bixa orellana) seeds are widely distributed throughout the Tropics and
      have been used to provide both colour and flavour to food. This study sought to
      assess the ability of dietary inclusion of polar (water) and non-polar
      (chloroform) extracts of Annatto (B. orellana) seeds on cyclophosphamide-induced
      oxidative stress in rat brain. The total phenol content and antioxidant
      activities of polar (water) and non-polar (chloroform) extracts of Annatto seeds
      were determined in vitro and in vivo. The results of the study showed that
      intraperitoneal administration of cyclophosphamide (75 mg/kg of body weight)
      caused a significant increase (P<0.05) in the malondialdehyde (MDA) content of
      the brain; however, dietary inclusion of Annatto seed extracts (0.1% and 0.2%)
      caused dose-dependent significant decrease (P<0.05) in the MDA content of the
      brain. Likewise, the extracts also caused dose-dependent inhibition of the
      elevated serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate
      transaminase (SGPT), alkaline phosphatase and total bilirubin. However, the non
      polar extract had significantly higher inhibitory effects on the elevated MDA
      production in brain and serum liver function markers. This higher protective
      effect of the non-polar extract could be attributed to its higher antioxidant
      properties as typified by its significantly higher (P<0.05) reducing power, free
      radical scavenging and Fe (II) chelating ability. Therefore, dietary inclusion of
      Annato seed extracts as food colourant could prevent oxidative stress occasioned
      by cyclophosphamide administration, but the non-polar extract is a better
      protectant.

PMID- 20137905
TI  - Infection and apoptosis as a combined inflammatory trigger.
AB  - While inflammatory phagocytosis of microbial pathogens and non-inflammatory
      phagocytosis of apoptotic cells have each been studied extensively, the
      consequences of innate immune recognition of host cells undergoing apoptosis as a
      direct result of infection are unclear. In this situation, the innate immune
      system is confronted with mixed signals, those from apoptotic cells and those
      from the infecting pathogen. Nuclear receptor activation has been implicated
      downstream of apoptotic cell recognition while Toll-like receptors are the
      prototypical inflammatory receptors engaged during infection. When the two
      signals combine, a new set of events takes place beginning with transrepression
      of a subset of inflammatory-response genes and ending with the induction of a T
      helper-17 adaptive immune response. This response is best suited for clearing the
      infecting pathogen and repairing the damage that occurred to the host tissue
      during infection.

PMID- 20137906
TI  - Innate antiviral immunity in Drosophila.
AB  - The study of Drosophila, and other genetically tractable insects, has expanded
      our understanding of innate immunity and more recently antiviral innate
      mechanisms. The Drosophila antiviral program includes inflammatory signaling
      cascades as well as antiviral RNA silencing and autophagy. This review will
      highlight the recent discoveries in antiviral immunity in insects and will reveal
      some of the lessons learned.

PMID- 20137907
TI  - Crucial roles of histone-modifying enzymes in mediating neural cell-type
      specification.
AB  - The development of the central nervous system (CNS) is governed by networks of
      extrinsic and intrinsic molecular programs that together orchestrate precise gene
      regulation. For the past few years, significant progress has been made in the
      characterization of histone-modifying enzymes and the roles they play in
      transcriptional control by affecting chromatin structure. Importantly, recent
      studies have revealed dynamic changes in histone modifications over the course of
      neural cell-fate specification. Further understanding of physiological functions
      of histone-modifying enzymes and their molecular mechanisms of action in CNS
      development will provide crucial insights into the process of generating neural
      cell types with tremendous diversity. Here we discuss the recent advancement in
      understanding the roles of enzymes involved in histone acetylation and
      methylation during neural cell-type specification.

PMID- 20137908
TI  - Adjuvant chemotherapy for early colon cancer: what survival benefits make it
      worthwhile?
AB  - BACKGROUND: We sought to determine the minimum survival benefits that patients
      judged sufficient to make adjuvant chemotherapy for early colon cancer
      worthwhile, factors associated with these judgments; and, to compare a self
      administered questionnaire with a validated, scripted interview. PATIENTS AND
      METHODS: One twenty three subjects who completed adjuvant chemotherapy for early
      colon cancer 3-60 months earlier completed a questionnaire; 97 were randomised to
      complete an interview before or after the questionnaire. Preferences were
      elicited by the time trade-off method in 4 hypothetical scenarios. Concordance
      between the interview and questionnaire was assessed with the intraclass
      correlation coefficient (ICC). RESULTS: Median age was 65 years (range 19-86),
      52% were female and 74% had involved lymph nodes. Over 60% of patients judged an
      additional 1 month beyond life expectancies of 5 years or 15 years, and an
      additional 1-2% beyond 5-year survival rates of 85% or 65%, sufficient to make
      chemotherapy worthwhile. Subjects with tertiary education (p=0.003) or aged 75
      years or less (p=0.02) judged larger benefits necessary to make chemotherapy
      worthwhile. Concordance between the interview and questionnaire was high (ICCs
      0.71-0.82). CONCLUSIONS: Most subjects judged small survival benefits sufficient
      to make adjuvant chemotherapy worthwhile. A self-administered questionnaire was a
      valid and acceptable way of eliciting preferences.

PMID- 20137909
TI  - Biogas production from co-digestion of dairy manure and food waste.
AB  - The effect of manure-screening on the biogas yield of dairy manure was evaluated
      in batch digesters under mesophilic conditions (35 degrees C). Moreover, the
      study determined the biogas production potential of different mixtures of
      unscreened dairy manure and food waste and compared them with the yield from
      manure or food waste alone. A first-order kinetics model was developed to
      calculate the methane yield from different mixtures of food waste and unscreened
      dairy manure. The methane yields of fine and coarse fractions of screened manure
      and unscreened manure after 30days were 302, 228, and 241L/kgVS, respectively.
      Approximately 93%, 87%, and 90% of the biogas yields could be obtained,
      respectively, after 20days of digestion. Average methane content of the biogas
      was 69%, 57%, and 66%, respectively. Based on mass balance calculations,
      separation of the coarse fraction of manure would sacrifice about 32% of the
      energy potential. The methane yield of the food waste was 353L/kgVS after 30days
      of digestion. Two mixtures of unscreened manure and food waste, 68/32% and
      52/48%, produced methane yields of 282 and 311L/kgVS, respectively after 30days
      of digestion. After 20days, approximately 90% and 95% of the final biogas yield
      could be obtained, respectively. Therefore, a hydraulic retention time (HRT) of
      20days could be recommended for a continuous digester. The average methane
      content was 62% and 59% for the first and second mixtures, respectively. The
      predicted results from the model showed that adding the food waste into a manure
      digester at levels up to 60% of the initial volatile solids significantly
      increased the methane yield for 20days of digestion.

PMID- 20137910
TI  - Characteristics of hydrogen production and substrate consumption of
      Rhodopseudomonas palustris CQK 01 in an immobilized-cell photobioreactor.
AB  - Effects of operation parameters on hydrogen production rate, substrate
      utilization efficiency and hydrogen bioconversion yield were investigated in a
      photobioreactor packed with sodium alginate/polyvinyl alcohol-124/carrageenan
      granules containing Rhodopseudomonas palustris CQK 01. Results demonstrate that
      an increase in influent glucose concentration and flow rate enhanced glucose
      transport from the bulk liquid into the granules, resulting in high hydrogen
      production. The bacteria mainly utilized the photo-heterotrophic pathway under
      optimal light illumination and produced hydrogen at low influent substrate
      loading, while they produced organic acids at high influent loading. The optimal
      temperature and pH of the influent medium for hydrogen production were
      independent of the illumination wavelength. The maximal hydrogen production rate
      of 2.61mmol/L/h was achieved under illumination at 590nm and 6000lx, a substrate
      concentration of 60mmol/L, a temperature of 30 degrees C and a pH7 of the
      influent medium.

PMID- 20137911
TI  - Enhanced l-phenylalanine biosynthesis by co-expression of pheA(fbr) and aroF(wt).
AB  - A beta-2-thienylalanine-resistant E. coli K12 mutant carrying a Thr326Pro
      mutation in the regulation (R) domain of pheA (pheA(fbr)) was obtained by N
      methyl-N'-nitro-N-nitrosoguanidine (NTG) mutagenesis. In the presence of 200mM l
      phenylalanine (l-Phe), a recombinant E. coli WSH-Z06 (pAP-B03) carrying pheA(fbr)
      as well as wild-type aroF (aroF(wt)) exhibited more than 70% of the chorismate
      mutase-prephenate dehydratase (CM-PDT) activity as observed in the absence of
      this amino acid. The l-Phe titer of WSH-Z06 (pAP-B03) reached 35.38g/L in a 3-L
      fermentor, which was 2.81-fold higher than that of the original strain E. coli
      WSH-Z06. Furthermore, the l-Phe yield on glucose of WSH-Z06 (pAP-B03)
      (0.26mol/mol) was twice that of E. coli WSH-Z06. This recombinant E. coli WSH-Z06
      (pAP-B03) is a potential strain for over-production of l-Phe.

PMID- 20137912
TI  - Municipal solid waste (MSW) as a renewable source of energy: current and future
      practices in China.
AB  - With rapid economic growth and massive urbanization, China faces the problem of
      municipal solid waste (MSW) disposal and the pressing need for development of
      alternative energy. Waste-to-energy (WTE) incineration, which recovers energy
      from discarded MSW and produces electricity and/or steam for heating, is
      recognized as a renewable source of energy and is playing an increasingly
      important role in MSW management in China. This article provides an overview of
      the WTE industry, discusses the major challenges in expanding WTE incineration in
      China, namely, high capital and operational costs, equipment corrosion, air
      pollutant emissions, and fly ash disposal. A perspective on MSW as a renewable
      energy source in China is also presented. Currently, only approximately 13% of
      MSW generated in China is disposed in WTE facilities. With the significant
      benefits of environmental quality, the reduction of greenhouse gas (GHG)
      emissions, and government policies and financial incentives as a renewable energy
      source, WTE incineration industry is expected to experience significant growth in
      the coming decade and make greater contribution to supplying renewable energy in
      China.

PMID- 20137913
TI  - Modelling the anaerobic digestion of wastewater derived from the pressing of
      orange peel produced in orange juice manufacturing.
AB  - A kinetic model of the anaerobic digestion of wastewater derived from the
      pressing of orange peel is proposed. The process was conducted in a laboratory
      scale, completely stirred tank reactor operating in batch mode at mesophilic
      temperature. The anaerobic biodegradability of the physical-chemical pre-treated
      wastewater was found to be 84%, while methane yield coefficient was 297NmL
      CH(4)/g COD removed. The mathematical model based on six segregated differential
      equations simulated the evolution of the concentration of carbon in different
      forms from biodegradable and non-biodegradable substrate. The transformation
      steps followed first or second-order kinetics. The kinetic constants
      corresponding to these stages were found to decrease markedly with the load added
      to the reactor, showing the occurrence of an inhibition process. The small
      deviations obtained between the experimental and simulated values demonstrated
      the suitability of the mathematical model in predicting the behaviour of the
      microorganisms involved in the anaerobic digestion of this wastewater.

PMID- 20137914
TI  - Nitrate and nitrite nitrogen determination in waste water using on-line UV
      spectrometric method.
AB  - A method is proposed for on-line UV spectroscopy and data analysis are applied to
      determine nitrate and nitrite nitrogen (NO(x)-N) in various waste water matrices.
      Comparison with standard analytical method was performed. Sensor calibration with
      pure substance reference materials delivered sufficient results for
      characteristic municipal waste water matrix, but for waste water with substantual
      industrial contribution and for landfill leachate matrix match calibration was
      required to enhance trueness. The described method concept is well suited for on
      line monitoring.

PMID- 20137915
TI  - Application of 3D scanned imaging methodology for volume, surface area, and
      envelope density evaluation of densified biomass.
AB  - Measurement of volume, surface area, and density is an essential for quantifying,
      evaluating, and designing the biomass densification, storage, and transport
      operations. Acquiring accurate and repeated measurements of these parameters for
      hygroscopic densified biomass are not straightforward and only a few methods are
      available. A 3D laser scanner was used as a measurement device and the 3D images
      were analyzed using image processing software. The validity of the method was
      verified using reference objects of known geometry and the accuracy obtained was
      in excess of 98%. Cotton gin trash briquettes, switchgrass pellets, switchgrass
      cubes, hardwood pellets, and softwood chips were tested. Most accurate results of
      the volume and surface area required the highest possible resolution of the
      scanner, which increased the total scan-process times, and image file size.
      Physical property determination using the 3D scanning and image analysis is
      highly repeatable (coefficient of variation <0.3%), non-invasive, accurate, and
      alternative methodology. The various limitations and merits of the developed
      method were also enumerated.

PMID- 20137916
TI  - Biofiltration of toluene using wood charcoal as the biofilter media.
AB  - A laboratory scale biofilter inoculated with Pseudomonas putida (MTCC 102) was
      used for degradation of toluene present in air. Wood charcoal was used as the
      filter media and a layer of glass beads (6mm) was used for improved air
      distribution. The biofilter was operated continuously for a period of 5months at
      four different flow rates - 0.06, 0.12, 0.18, and 0.24m(3)h(-1), with inlet
      concentration of toluene ranging from 0.04 to 4.5gm(-3). Air having toluene vapor
      was fed to the biofilter at various loadings ranging from 30.6 to 1104.5gm(-3)h(
      1). The removal efficiency was obtained in the range of 70-99.5%. The maximum
      elimination capacity of 872.5gm(-3)h(-1) was observed at the inlet load of
      1104.5gm(-3)h(-1). Wood charcoal was found to an effective biofilter media for
      toluene biodegradation.

PMID- 20137917
TI  - Population dynamics in a sequencing batch reactor fed with glucose and operated
      for enhanced biological phosphorus removal.
AB  - The study investigated the effect of glucose feeding as the sole carbon source on
      population dynamics in a sequencing batch reactor (SBR) operated for enhanced
      biological phosphorus removal (EBPR). The lab-scale SBR operation was started
      with a biomass taken from a WWTP plant performing EBPR and continued around two
      months. It exhibited a sequence of periods with different performance and biomass
      characteristics. The first period indicated predominant EBPR activity, involving
      phosphorus release in the anaerobic phase with PHA production as expected.
      Lactate generated from glucose fermentation was presumably converted to PHA by
      PAOs as an essential part of the EBPR activity. In the second period a major
      shift occurred in the population dynamics favoring the preferential growth and
      the predominance of GAOs which have the advantage of utilizing glucose directly
      and eventually the EBPR activity was deteriorated. The significant feature of the
      third period was the proliferation of filamentous microorganisms.

PMID- 20137918
TI  - Biological nutrient removal in an MBR treating municipal wastewater with special
      focus on biological phosphorus removal.
AB  - The performance of an MBR pilot plant for biological nutrient removal was
      evaluated during 210days of operation. The set point values for the internal
      recycles were determined in advance with the use of an optimisation spreadsheet
      based on the ASM2d model to optimise the simultaneous removal of C, N and P. The
      biological nutrient removal (BNR) efficiencies were high from the start of
      operation with COD and N removal efficiencies of 92+/-6% and 89+/-7,
      respectively. During the course of the experiment P removal efficiencies
      increased and finally a P-removal efficiency of 92% was achieved. The activity of
      poly-phosphate accumulating organisms (PAOs) and denitrifying poly-phosphate
      accumulating organisms (DPAOs) increased and the specific phosphate accumulation
      rates after 150days of operation amounted to 13.6mgPg(-1)VSSh(-1) and 5.6mgPg(
      1)VSSh(-1), for PAOs and DPAOs, respectively.

PMID- 20137919
TI  - Fouling characteristics in a membrane bioreactor coupled with anaerobic-anoxic
      oxic process for coke wastewater treatment.
AB  - Experiments were conducted to investigate the fouling characteristics of a
      membrane bioreactor combined with anaerobic-anoxic-oxic process for coke
      wastewater treatment. Supernatant from the oxic tank was characterized as
      different hydrophilic/hydrophobic fractions by DAX-8 resin, with joint size
      partition also undertaken. Polysaccharides and proteins, mainly the fraction with
      molecular weight above 100kDa, were liable to accumulate in the supernatant.
      Hydrophilic fraction, mainly contributing to the subclass of molecular weight
      above 100kDa, was found most likely responsible for the flux deterioration by
      means of dead-end filtration tests. Analyses of particle and membrane pore size
      distribution revealed that major foulants had size comparable to the pore
      diameter. It can be inferred that steric factor (i.e. size exclusion) behaved
      primarily in the initial stage of fouling, while the role of hydrophobic
      interaction was of less significance.

PMID- 20137920
TI  - Triacetonamine formation in a bio-oil from fast pyrolysis of sewage sludge using
      acetone as the absorption solvent.
AB  - A sewage sludge sample was pyrolyzed in a drop tube furnace at 500 degrees C and
      sweeping gas flow rate of 300cm(3)/min. Triacetonamine (TAA) was detected with
      GC/MS as major component in the resulting bio-oil using acetone as the absorption
      solvent and proven to be a product from the reaction of NH(3) in the bio-oil with
      the absorption solvent acetone. TAA yield increased with storage time and reached
      a level about 28.4% (% sludge fed, daf) after 175h. Since the reaction of pure
      NH(3) with acetone does not proceed, some species in the bio-oil must catalyze
      the reaction of NH(3) with acetone. TAA was isolated in a high yield (27.9%, daf)
      and high purity (80.4%) by column chromatography with different solvents,
      including mixed solvents, as eluants. The study revealed the possibility of
      sewage sludge as potential resource of TAA.

PMID- 20137921
TI  - Electricity generation by two types of microbial fuel cells using nitrobenzene as
      the anodic or cathodic reactants.
AB  - The effect of nitrobenzene (NB) on electricity generation and simultaneous
      biodegradation of NB were studied with two types of microbial fuel cells (MFCs):
      a ferricyanide-cathode MFC with NB as the anodic reactant and a NB-cathode MFC.
      Compared to controls without NB, the presence of NB in the anode of the first MFC
      decreased maximum voltage outputs, maximum power densities and Coulombic
      efficiencies. No electricity was generated from the first MFC using NB as the
      sole fuel; however, the second MFC using NB as the electron acceptor generated
      electricity successfully with a maximum voltage of 400mV. NB was degraded
      completely within 24h in both anode and cathode chambers. Denaturing gradient gel
      electrophoresis (DGGE) profiles demonstrated that the presence of NB caused
      changes in relative abundance of the dominant bacterial species and emergence of
      new bacteria on the anodes.

PMID- 20137922
TI  - Mine wastewater treatment using Phalaris arundinacea plant material hydrolyzate
      as substrate for sulfate-reducing bioreactor.
AB  - A low-cost substrate, Phalaris arundinacea was acid hydrolyzed (Reed Canary Grass
      hydrolyzate, RCGH) and used to support sulfate reduction. The experiments
      included batch bottle assays (35 degrees C) and a fluidized-bed bioreactor (FBR)
      experiment (35 degrees C) treating synthetic mine wastewater. Dry plant material
      was also tested as substrate in batch bottle assays. The batch assays showed
      sulfate reduction with the studied substrates, producing 540 and 350mgL(-1)
      dissolved sulfide with RCGH and dry plant material, respectively. The soluble
      sugars of the RCGH presumably fermented into volatile fatty acids and hydrogen,
      which served as electron donors for sulfate reducing bacteria. A sulfate
      reduction rate of 2.2-3.3gL(-1)d(-1) was obtained in the FBR experiment. The
      acidic influent was neutralized and the highest metal precipitation rates were
      0.84g FeL(-1)d(-1) and 15mg ZnL(-1)d(-1). The sulfate reduction rate in the FBR
      was limited by the acetate oxidation rate of the sulfate-reducing bacteria.

PMID- 20137923
TI  - Catalytic conversion of sugarcane bagasse, rice husk and corncob in the presence
      of TiO2, ZrO2 and mixed-oxide TiO2-ZrO2 under hot compressed water (HCW)
      condition.
AB  - The simultaneous hydrolysis/dehydration reaction of sugarcane bagasse, rice husk
      and corncob was studied under hot compressed water in the presence of TiO(2),
      ZrO(2) and TiO(2)-ZrO(2) at 473-673K. Among them, the reaction of corncob at 573K
      in the presence of TiO(2)-ZrO(2) produced the highest furfural and 5
      hydroxymethylfurfural (HMF) yields (10.3% and 8.6%) with less by-products (i.e.
      glucose, fructose, xylose, and 1,6-anhydroglucose) selectivities. It was found
      that the catalyst preparation procedure and calcination temperature strongly
      affected its reactivity. Catalysts prepared by (co-) precipitation method gained
      higher reactivity than those prepared by sol-gel and physical mixing methods. The
      suitable calcination temperature for TiO(2) and ZrO(2) was at 773K, whereas that
      for TiO(2)-ZrO(2) was at 873K; the XRD patterns revealed that different portions
      of phase formation were observed over catalysts with different calcination
      temperature. The portion of these phase formations affected the acidity-basicity
      of catalyst and thus the catalyst reactivity.

PMID- 20137924
TI  - Study on a novel non-dissolved redox mediator catalyzing biological
      denitrification (RMBDN) technology.
AB  - There are little literatures about the accelerating effect of redox mediators on
      the denitrification processes. In this paper, a novel non-dissolved redox
      mediator catalyzing biological denitrification (RMBDN) technology was first
      explored, and the accelerating effect of redox mediator on the denitrification
      processes was conducted with immobilized anthraquinone. Anthraquinone as a redox
      mediator was able to increase the denitrification rate, and was immobilized by
      entrapment in calcium alginate (CA). The results suggested that the artificial
      redox mediator anthraquinone was found to be capable of raising about 2-fold
      denitrification rate, and the stabilized oxidation-reduction potential (ORP)
      values with anthraquinone immobilization beads were lower around 20mV than the
      control without anthraquinone immobilization beads. The results of repeated-batch
      operations shown that anthraquinone immobilization beads appeared to exhibit good
      reusability. The study explored a great improvement of the redox mediator
      application and the new bio-treatment concept for the denitrification processes.

PMID- 20137925
TI  - Fractionation of process water in thermomechanical pulp mills.
AB  - In this work process water from a thermomechanical pulp mill was divided into
      five fractions by filtration and membrane filtration. Suspended matter was mainly
      isolated in the retentate from the drum filter, extractives in the
      microfiltration retentate, hemicelluloses in the ultrafiltration retentate and
      lignin in the nanofiltration retentate. The final water fraction was of fresh
      water quality. For each tonne of pulp produced, about 10kg of suspended matter,
      more than 0.3kg of extractives, 11kg of hemicelluloses and 8kg of aromatic
      compounds (lignin) could be recovered from the drum filtration retentate, the
      microfiltration retentate, the ultrafiltration retentate and the nanofiltration
      retentate, respectively. About 40% of the treated process water could be
      recovered as fresh water.

PMID- 20137926
TI  - SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase
      inhibitors.
AB  - Elevated stearoyl-CoA desaturase (SCD) activity has been linked to a number of
      metabolic disorders including obesity and type II diabetes. Compound 3j, a potent
      SCD inhibitor (human HepG2 IC(50)=1nM) was identified from the optimization of a
      lead thiazole compound MF-152 with over 100-fold improvement in potency. In a 4
      week chronic oral dosing at 0.2mg/kg, 3j gave a robust 24% prevention of body
      weight gain in mice fed on a high fat diet accompanied with an improved metabolic
      profile on insulin and glucose levels.

PMID- 20137927
TI  - Novel tetrahydrochinoline derived CETP inhibitors.
AB  - In the course of our efforts to identify orally active cholesteryl ester transfer
      protein (CETP) inhibitors, we have continued to explore tetrahydrochinoline
      derivatives. Based on BAY 19-4789 structural modifications led to the discovery
      of novel cycloalkyl substituted compounds. Thus, example 11b is a highly potent
      CETP inhibitor both in vitro and in vivo in transgenic mice with favourable
      pharmacokinetic properties for clinical development.

PMID- 20137928
TI  - N1-Heterocyclic pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse
      transcriptase.
AB  - A series of N1-heterocyclic pyrimidinediones were extensively evaluated as HIV-1
      non-nucleoside reverse transcriptase inhibitors (NNRTIs). Inhibitor 1 is active
      against NNRTI-resistant viruses including RT mutant K103N. The co-crystal
      structure of inhibitor 1 with HIV-1 RT revealed that H-bonds are formed with K101
      and K103. Efforts to improve the suboptimal pharmacokinetic profile of 1 resulted
      in the discovery of compound 13, which represents the lead compound in this
      series with improved pharmacokinetics and similar potency as inhibitor 1.

PMID- 20137929
TI  - Exploration of a new series of PAR1 antagonists.
AB  - Two series of new PAR1 antagonists have been identified. The first incorporates a
      cinnamoylpiperidine motif and the second a cinnamoylpyridine pattern. The
      synthesis, biological activity and structure-activity relationship of these
      compounds are presented. In each series, one analog showed potent in vivo
      antithrombotic activity in a rat AV shunt model, with up to 53% inhibition at
      1.25mpk iv for compound 30.

PMID- 20137930
TI  - Absolute configurations of tubulin inhibitors taltobulin (HTI-286) and HTI-042
      characterized by X-ray diffraction analysis and NMR studies.
AB  - The stereochemistry of the tubulin inhibitors taltobulin HTI-286 (2) and HTI-042
      (3) was determined by utilizing the DPFGSE 1D NOE experiment. Single crystal X
      ray diffraction analysis further confirmed the absolute configuration of these
      two compounds, which carry the (S,S,S)-configuration necessary for biological
      activity.

PMID- 20137931
TI  - Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase
      inhibitor to a DFG-out binding mode.
AB  - The work described herein demonstrates the utility of structure-based drug design
      (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out
      binding mode resulting in a class of novel potent CSF-1R kinase inhibitors
      suitable for lead development.

PMID- 20137932
TI  - 2-Aminothiadiazole inhibitors of AKT1 as potential cancer therapeutics.
AB  - A series of 2-aminothiadiazole of inhibitors of AKT1 is described. SAR
      relationships are discussed, along with selectivity for protein kinase A (PKA)
      and cyclin-dependent kinase 2 (CDK2). Moderate selectivity observed in several
      compounds for AKT1 versus PKA is rationalized by X-ray crystallographic analysis.
      Key compounds showed activity in cellular assays measuring phosphorylation of two
      AKT substrates, PRAS40 and FKHRL1. Compound 30 was advanced to a mouse liver PD
      assay, where it showed dose-dependent inhibition of AKT activity, as measured by
      the inhibition of phospho-PRAS40.

PMID- 20137933
TI  - Identification of piperazine-bisamide GHSR antagonists for the treatment of
      obesity.
AB  - Piperazine-bisamide analogs were discovered as partial agonists of human growth
      hormone secretagogue receptor (GHSR) in a high throughput screen. The partial
      agonists were optimized for potency and converted into antagonists through
      structure-activity relationship (SAR) studies. The efforts also led to the
      identification of potent antagonist with favorable PK profile suitable as a tool
      compound for in vivo studies.

PMID- 20137934
TI  - Design, synthesis, evaluation and QSAR analysis of N(1)-substituted norcymserine
      derivatives as selective butyrylcholinesterase inhibitors.
AB  - We synthesized a series of N(1)-substituted norcymserine derivatives 7a-p and
      evaluated their anti-cholinesterase activities. In vitro evaluation showed that
      the pyridinylethyl derivatives 7m-o and the piperidinylethyl derivative 7p
      improved the anti-butyrylcholinesterase activity by approximately threefold
      compared to N(1)-phenethylnorcymserine (PEC, 2). A quantitative structure
      activity relationship (QSAR) study indicated that logS might be a key feature of
      the improved compounds.

PMID- 20137935
TI  - Synthesis, SAR and intramolecular hydrogen bonding pattern of 1,3,5
      trisubstituted 4,5-dihydropyrazoles as potent cannabinoid CB(1) receptor
      antagonists.
AB  - The synthesis, structure-activity relationship (SAR) studies and intramolecular
      hydrogen bonding pattern of 1,3,5-trisubstituted 4,5-dihydropyrazoles are
      described. The target compounds 6-18 represent a novel class of potent and
      selective CB(1) receptor antagonists. Based on X-ray diffraction data, the orally
      active 17 is shown to elicit a different intramolecular H-bonding mode as
      compared to ibipinabant (3) and SLV330 (4).

PMID- 20137936
TI  - Radiosynthesis of novel carbon-11-labeled triaryl ligands for cannabinoid-type 2
      receptor.
AB  - Two novel triaryl ligands 2 and 5 with potent in vitro binding affinities for the
      cannabinoid subtype-2 (CB2) receptor were labeled with a positron-emitting
      radioactive nuclide (11)C. Radioligands [(11)C]2, [(11)C]5, and their analogs
      [(11)C]3 and [(11)C]4 were synthesized by O-[(11)C]methylation of their
      corresponding phenol precursors with [(11)C]CH(3)I. [(11)C]2-5 had relatively
      high uptakes (>1.2% injected dose/g tissue) in mouse brains.

PMID- 20137937
TI  - Evaluation of a 3-amino-8-azabicyclo[3.2.1]octane replacement in the CCR5
      antagonist maraviroc.
AB  - The bicyclic 5-amino-3-azabicyclo[3.3.0]octanes were shown to be effective
      replacements for the 3-amino-8-azabicyclo[3.2.1]octane found in the CCR5
      antagonist maraviroc.

PMID- 20137938
TI  - Novel multiple opioid ligands based on 4-aminobenzazepinone (Aba), azepinoindole
      (Aia) and tetrahydroisoquinoline (Tic) scaffolds.
AB  - The dimerization and trimerization of the Dmt-Tic, Dmt-Aia and Dmt-Aba
      pharmacophores provided multiple ligands which were evaluated in vitro for opioid
      receptor binding and functional activity. Whereas the Tic- and Aba multimers
      proved to be dual and balanced delta/mu antagonists, as determined by the
      functional [S(35)]GTPgammaS binding assay, the dimerization of potent Aia-based
      'parent' ligands unexpectedly resulted in substantial less efficient receptor
      binding and non-active dimeric compounds.

PMID- 20137939
TI  - Design, synthesis and biological evaluation of estradiol-chlorambucil hybrids as
      anticancer agents.
AB  - A series of estradiol-chlorambucil hybrids was synthesized as anticancer drugs
      for site-directed chemotherapy of breast cancer. The novel compounds were
      synthesized in good yields through efficient modifications of estrone at position
      16alpha of the steroid nucleus. The newly synthesized compounds were evaluated
      for their anticancer efficacy in different hormone-dependent and hormone
      independent breast cancer cell lines. The novel hybrids showed significant in
      vitro anticancer activity when compared to chlorambucil. Structure-activity
      relationship (SAR) reveals the influence of the length of the spacer chain
      between carrier and drug molecule.

PMID- 20137940
TI  - 2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or
      p97).
AB  - Valosin-containing protein (VCP; also known as p97) is a member of the AAA ATPase
      family with a central role in the ubiquitin-degradation of misfolded proteins.
      VCP also exhibits antiapoptotic function and metastasis via activation of nuclear
      factor kappa-B signaling pathway. We have discovered that 2-anilino-4-aryl-1,3
      thiazoles are potent drug-like inhibitors of this enzyme. The identified
      compounds show low nanomolar VCP potency, demonstrate SAR trends, and show
      activity in a mechanism based cellular assay. This series of compounds represents
      the first steps towards a novel, small molecule VCP inhibitor as a cancer
      therapeutic.

PMID- 20137941
TI  - Design, synthesis and evaluation of carbamate-modified (-)-N(1)
      phenethylnorphysostigmine derivatives as selective butyrylcholinesterase
      inhibitors.
AB  - We synthesized carbamate-modified (-)-N(1)-phenethylnorphysostigmine derivatives
      3a-u and evaluated their anti-cholinesterase activities. In vitro evaluation
      showed that cyclohexylmethylcarbamate derivative 3u potently and selectively
      inhibits butyrylcholinesterase.

PMID- 20137942
TI  - Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2
      antagonists.
AB  - The SAR features have been further explored for (2-benzhydryl-4-phenyl-thiazol-5
      yl)acetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed
      on Th2 cells) antagonists. The introduction of a nitrogen or a methyl substituent
      in the benzhydrylic position offer two alternative drugable scaffolds attractive
      for unsymmetrically substituted derivatives. An imidazole analogue lacks activity
      due to formation of a favored coplanar intramolecular hydrogen bond. The
      pyrimidine derivative 18 represents a potent and selective compound that will be
      subject to continued investigations.

PMID- 20137943
TI  - Azole-based inhibitors of AKT/PKB for the treatment of cancer.
AB  - Through a combination of screening and structure-based rational design, we have
      discovered a series of N(1)-(5-(heterocyclyl)-thiazol-2-yl)-3-(4
      trifluoromethylphenyl)-1,2-propanediamines that were developed into potent ATP
      competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres
      identified SAR trends in potency and selectivity that were consistent with
      binding interactions observed in structures of the inhibitors bound to AKT1 and
      to the counter-screening target PKA. One compound was shown to have acceptable
      pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of
      in vivo xenograft tumor growth in a preclinical model of glioblastoma.

PMID- 20137944
TI  - Decahydroisoquinoline derivatives as novel non-peptidic, potent and subtype
      selective somatostatin sst(3) receptor antagonists.
AB  - Starting from non-peptidic sst(1)-selective somatostatin receptor antagonists,
      first compounds with mixed sst(1)/sst(3) affinity were identified by directed
      structural modifications. Systematic optimization of these initial leads afforded
      novel, enantiomerically pure, highly potent and sst(3)-subtype selective
      somatostatin antagonists based on a (4S,4aS,8aR)-decahydroisoquinoline-4
      carboxylic acid core moiety. These compounds can efficiently be synthesized and
      show promising PK properties in rodents.

PMID- 20137945
TI  - Synthetic atpenin analogs: Potent mitochondrial inhibitors of mammalian and
      fungal succinate-ubiquinone oxidoreductase.
AB  - Atpenins and harzianopyridone represent a unique class of penta-substituted
      pyridine-based natural products that are potent inhibitors of complex II
      (succinate-ubiquinone oxidoreductase) in the mitochondrial respiratory chain.
      These compounds block electron transfer in oxidative phosphorylation by
      inhibiting oxidation of succinate to fumarate and the coupled reduction of
      ubiquinone to ubiquinol. From our investigations of complex II inhibitors as
      potential agricultural fungicides, we report here on the synthesis and complex II
      inhibition for a series of synthetic atpenin analogs against both mammalian and
      fungal forms of the enzyme. Synthetic atpenin 2e provided optimum mammalian and
      fungal inhibition with slightly higher potency than natural occurring atpenin A5.

PMID- 20137946
TI  - Discovery of N-(5,6-diarylpyridin-2-yl)amide derivatives as potent and selective
      A(2B) adenosine receptor antagonists.
AB  - The synthesis and SAR of a series of N-(5,6-diarylpyridin-2-yl)amide derivatives
      as potent A(2B) adenosine receptor antagonists is described. Several compounds
      showed good selectivity versus other adenosine receptors. The potent and
      selective analogue 9 was shown to have good oral bioavailability in the rat.

PMID- 20137947
TI  - Carbonic anhydrase inhibitors. Inhibition of transmembrane isoforms IX, XII, and
      XIV with less investigated anions including trithiocarbonate and dithiocarbamate.
AB  - An inhibition study of the transmembrane carbonic anhydrase (CA, EC 4.2.1.1)
      isoforms IX, XII (tumor-associated), and XIV with anions such as stannate(IV),
      selenate(VI), tellurate(VI), perosmate(VIII), persulfate, pyrophosphate(V),
      pyrovanadate(V), tetraborate, persulfate, perrhenate(VII), perrutenate(VII),
      selenocyanate, iminodisulfonate, fluorosulfate, and trithiocarbonate is reported.
      Selenate, perosmate, and pyrophosphate were ineffective inhibitors, whereas most
      of these anions inhibited the three enzymes in the millimolar-submillimolar
      range. Trithiocarbonate and diethyldithiocarbamate were the best CA IX inhibitors
      (K(I)s of 1.4-9.7microM), but trithiocarbonate showed less affinity for CA XII
      and XIV (K(I)s of 0.12-0.66mM). N,N-Diethyldithiocarbamate was a low micromolar
      inhibitor also against CA XII and XIV (K(I)s of 1.0-1.1microM), suggesting that
      this new zinc-binding group (CS2-) may lead to efficient inhibitors targeting
      transmembrane CAs.

PMID- 20137948
TI  - In vivo coupling of cell elongation and lumen formation in a single cell.
AB  - Fine tubes form inside cells as they reach their target tissues in epithelial
      ducts and in angiogenesis. Although a very suggestive model of cell hollowing
      proposes that intracellular lumen could arise by coalescence of intracellular
      vacuoles, how those tubes form in vivo remains an open question. We addressed
      this issue by examining intracellular lumen formation in the Drosophila trachea.
      The main branches of the Drosophila tracheal system have an extracellular lumen
      because their cells fold to form a tube. However, terminal cells, specialized
      cells in some of the main branches, form unicellular branches by the generation
      of an intracellular lumen. Conversely to the above-mentioned model, we find that
      the intracellular lumen arises by growth of an apical membrane inwards the cell.
      In support, we detect an appropriate subcellular compartmentalization of
      different components of the intracellular trafficking machinery. We show that
      both cellular elongation and lumen formation depend on a mechanism based on
      asymmetric actin accumulation and microtubule network organization. Given the
      similarities in the formation of fine respiratory tubes and capillaries, we
      propose that an inward membrane growth model could account for lumen formation in
      both processes.

PMID- 20137949
TI  - Cell-nonautonomous regulation of C. elegans germ cell death by kri-1.
AB  - Programmed cell death (or apoptosis) is an evolutionarily conserved, genetically
      controlled suicide mechanism for cells that, when deregulated, can lead to
      developmental defects, cancers, and degenerative diseases. In C. elegans, DNA
      damage induces germ cell death by signaling through cep-1/p53, ultimately leading
      to the activation of CED-3/caspase. It has been hypothesized that the major
      regulatory events controlling cell death occur by cell-autonomous mechanisms,
      that is, within the dying cell. In support of this, genetic studies in C. elegans
      have shown that the core apoptosis pathway genes ced-4/APAF-1 and ced-3/caspase
      are required in cells fated to die. However, it is not known whether the upstream
      signals that activate apoptosis function in a cell-autonomous manner. Here we
      show that kri-1, an ortholog of KRIT1/CCM1, which is mutated in the human
      neurovascular disease cerebral cavernous malformation, is required to activate
      DNA damage-dependent cell death independently of cep-1/p53. Interestingly, we
      find that kri-1 regulates cell death in a cell-nonautonomous manner, revealing a
      novel regulatory role for nondying cells in eliciting cell death in response to
      DNA damage.

PMID- 20137950
TI  - Mixed microtubules steer dynein-driven cargo transport into dendrites.
AB  - BACKGROUND: To establish and maintain their polarized morphology, neurons employ
      active transport driven by molecular motors to sort cargo between axons and
      dendrites. However, the basic traffic rules governing polarized transport on
      neuronal microtubule arrays are unclear. RESULTS: Here we show that the
      microtubule minus-end-directed motor dynein is required for the polarized
      targeting of dendrite-specific cargo, such as AMPA receptors. To directly examine
      how dynein motors contribute to polarized dendritic transport, we established a
      trafficking assay in hippocampal neurons to selectively probe specific motor
      protein activity. This revealed that, unlike kinesins, dynein motors drive cargo
      selectively into dendrites, governed by their mixed microtubule array. Moreover,
      axon-specific cargos, such as presynaptic vesicle protein synaptophysin, are
      redirected to dendrites by coupling to dynein motors. Quantitative modeling
      demonstrated that bidirectional dynein-driven transport on mixed microtubules
      provides an efficient mechanism to establish a stable density of continuously
      renewing vesicles in dendrites. CONCLUSIONS: These results demonstrate a powerful
      approach to study specific motor protein activity inside living cells and imply a
      key role for dynein in dendritic transport. We propose that dynein establishes
      the initial sorting of dendritic cargo and additional motor proteins assist in
      subsequent delivery.

PMID- 20137951
TI  - Centrosome size sets mitotic spindle length in Caenorhabditis elegans embryos.
AB  - Just as the size of an organism is carefully controlled, the size of
      intracellular structures must also be regulated. The mitotic spindle is a
      supramolecular machine that generates the forces which separate sister chromatids
      during mitosis. Although spindles show little size variation between cells of the
      same type, spindle length can vary at least 10-fold between different species.
      Recent experiments on spindle length showed that in embryonic systems spindle
      length varied with blastomere size. Furthermore, a comparison between two Xenopus
      species showed that spindle length was dependent on some cytoplasmic factor.
      These data point toward mechanisms to scale spindle length with cell size.
      Centrosomes play an important role in organizing microtubules during spindle
      assembly. Here we use Caenorhabditis elegans to study the role of centrosomes in
      setting spindle length. We show that spindle length correlates with centrosome
      size through development and that a reduction of centrosome size by molecular
      perturbation reduces spindle length. By systematically analyzing centrosome
      proteins, we show that spindle length does not depend on microtubule density at
      centrosomes. Rather, our data suggest that centrosome size sets mitotic spindle
      length by controlling the length scale of a TPXL-1 gradient along spindle
      microtubules.

PMID- 20137952
TI  - The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates
      protrusive invasion.
AB  - Fascin is an actin-bundling protein involved in filopodia assembly and cancer
      invasion and metastasis of multiple epithelial cancer types. Fascin forms stable
      actin bundles with slow dissociation kinetics in vitro and is regulated by
      phosphorylation of serine 39 by protein kinase C (PKC). Cancer cells use invasive
      finger-like protrusions termed invadopodia to invade into and degrade
      extracellular matrix. Invadopodia have highly dynamic actin that is assembled by
      both Arp2/3 complex and formins; they also contain components of membrane
      trafficking machinery such as dynamin and cortactin and have been compared with
      focal adhesions and podosomes. We show that fascin is an integral component of
      invadopodia and that it is important for the stability of actin in invadopodia.
      The phosphorylation state of fascin at S39, a PKC site, contributes to its
      regulation at invadopodia. We further implicate fascin in invasive migration into
      collagen I-Matrigel gels and particularly in cell types that use an elongated
      mesenchymal type of motility in 3D. We provide a potential molecular mechanism
      for how fascin increases the invasiveness of cancer cells, and we compare
      invadopodia with invasive filopod-like structures in 3D.

PMID- 20137953
TI  - NuMA after 30 years: the matrix revisited.
AB  - The large nuclear mitotic apparatus (NuMA) protein is an abundant component of
      interphase nuclei and an essential player in mitotic spindle assembly and
      maintenance. With its partner, cytoplasmic dynein, NuMA uses its cross-linking
      properties to tether microtubules to spindle poles. NuMA and its invertebrate
      homologs play a similar tethering role at the cell cortex, thereby mediating
      essential asymmetric divisions during development. Despite its maintenance as a
      nuclear component for decades after the final mitosis of many cell types
      (including neurons), an interphase role for NuMA remains to be established,
      although its structural properties implicate it as a component of a nuclear
      scaffold, perhaps as a central constituent of the proposed nuclear matrix.

PMID- 20137954
TI  - Maturation of eukaryotic ribosomes: acquisition of functionality.
AB  - In eukaryotic cells, ribosomes are pre-assembled in the nucleus and exported to
      the cytoplasm where they undergo final maturation. This involves the release of
      trans-acting shuttling factors, transport factors, incorporation of the remaining
      ribosomal proteins, and final rRNA processing steps. Recent work, particularly on
      the large (60S) ribosomal subunit, has confirmed that the 60S subunit is exported
      from the nucleus in a functionally inactive state. Its arrival in the cytoplasm
      triggers events that render it translationally competent. Here we focus on these
      cytoplasmic maturation events and speculate why eukaryotic cells have evolved
      such an elaborate maturation pathway.

PMID- 20137955
TI  - Insight into the strong inhibitory action of salt on activity of
      neocarzinostatin.
AB  - Enediyne anticancer drugs belong to one of the most potent category in inducing
      DNA damage. We report 85+/-5% inhibition on activity of neocarzinostatin by salt.
      As high sodium ion concentration is a known tumor cell feature, we explored the
      dynamic mechanism of inhibition. Using various analytical tools, we examined
      parameters involved in the four consecutive steps of the drug action, namely,
      drug releasing from carrier protein, drug-DNA binding, drug activating, and DNA
      damaging. Neither protein stability, nor drug release rate, was altered by salt.
      The salt inhibition level was similar in between the protein-bound and unbound
      enediyne chromophore. Salt did not quench the thiol-induced drug activation. The
      inhibition was independent of DNA lesion types and irrelevant with thiol
      structures. Collectively, no salt interaction was found in the releasing,
      activating, and DNA damaging step of the drug action. However, binding with DNA
      decreased linearly with salt and corresponded well with the salt-induced
      inhibition on the drug activity. Salt interference on the affinity of DNA binding
      was the main and sole cause of the severe salt inhibition. The inhibition factor
      should be carefully considered for all agents with similar DNA binding mode.

PMID- 20137956
TI  - Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols.
AB  - Plants are an important source of a variety of bioactive compounds with different
      modes of action. Anti-HIV agents from plant sources can be useful in developing
      novel therapies for inhibiting HIV infection. Based on the reported anti-HIV
      activity of plant derived phloroglucinols, several new dimeric phloroglucinols
      were synthesized in the present study by varying substitution on aromatic ring
      and at methylene bridge. Some of the synthesized compounds have shown good HIV
      inhibitory activity in a human CD4+ T cell line (CEM-GFP) infected with HIV-1
      NL(4.3) virus isolate. Structure-activity studies indicate that phenyl, 4
      benzyloxy-1-phenyl and cyclohexyl substitution at methylene bridge gave compounds
      with better anti-HIV activity. Compounds 22 and 24 showed highest anti-HIV
      activity with an IC(50) of 0.28 microM and 2.71 microM, respectively, former was
      more active than the positive standard AZT in cell based assay.

PMID- 20137957
TI  - Synthesis and pharmacological evaluation of novel 1,3,8- and 1,3,7,8-substituted
      xanthines as adenosine receptor antagonists.
AB  - A number of novel xanthines bearing a variety of substituents at positions 1, 3,
      7 and 8 were prepared and evaluated for their binding affinity to the human
      adenosine receptor A(1), A(2A), A(2B) and A(3) subtypes. Several of the 1,3,8-
      and 1,3,7,8-substituted xanthines showed moderate-to-high affinity at human A(2B)
      and A(1) receptors, with the most active compound (14q) having a pK(i) of 7.57 nM
      for hA(2B) receptors and a selectivity over hA(2A) receptors of 8.1-fold and
      hA(1) receptors of 3.7-fold.

PMID- 20137958
TI  - Synthesis and analysis of 2-[211At]-L-phenylalanine and 4-[211At]-L-phenylalanine
      and their uptake in human glioma cell cultures in-vitro.
AB  - 2-[211At]-L-phenylalanine and 4-[211At]-L-phenylalanine were prepared from the
      corresponding iodo and bromo derivatives using the Cu(+)-assisted nucleophilic
      exchange. 4-[211At]-L-phenylalanine was additionally prepared by destannylation
      of the BOC-derivatized 4-tributylstannyl-L-phenylalanine. Radiochemical yields of
      2-[211At]-L-phenylalanine and 4-[211At]-L-phenylalanine by nucleophilic exchange
      were 52-74% and 65-85%. Radiochemical yield of 4-[211At]-L-phenylalanine by
      electrophilic destannylation was 35-50%. HPLC sequence analysis showed that 2
      [211At]-L-phenylalanine followed the halogen sequence (F<Cl<Br<I<At) whereas 4
      [211At]-L-phenylalanine eluted between 4-Br-L-phenylalanine and 4-I-L
      phenylalanine (F<Cl<Br<At<I), independent on the production pathway. Uptake of 4
      [211At]-L-phenylalanine and 4-[131I]-L-phenylalanine in DBTRG-05MG glioma cells
      was inhibited by l-phenylalanine 7-fold and 6-fold, respectively.

PMID- 20137959
TI  - The cellular redox state in plant stress biology--a charging concept.
AB  - Different redox-active compounds, such as ascorbate, glutathione, NAD(P)H and
      proteins from the thioredoxin superfamily, contribute to the general redox
      homeostasis in the plant cell. The myriad of interactions between redox-active
      compounds, and the effect of environmental parameters on them, has been
      encapsulated in the concept of a cellular redox state. This concept has
      facilitated progress in understanding stress signalling and defence in plants.
      However, despite the proven usefulness of the concept of a redox state, there is
      no single, operational definition that allows for quantitative analysis and
      hypothesis testing.

PMID- 20137960
TI  - Microscopic and biochemical evidence of differentially virulent field isolates of
      Diplocarpon rosae causing black spot disease of roses.
AB  - Black spot disease caused by Diplocarpon rosae is one of the most widespread
      diseases of roses that are very difficult to control due to the generative
      reproduction and complex genetic constitution of roses and up to now the control
      of black spot still requires intensive use of systemic fungicides. Here we report
      for the first time evidence of differentially virulent field isolates of D.
      rosae. Using a combination of fungal structures, disease symptoms and host cells
      protein expression pattern analysis we here provide direct biochemical evidence
      that tropical field isolates of D. rosae are more virulent and caused disease
      symptoms earlier than their temperate counterparts. The tropical fungal field
      isolates strongly induced an excessive accumulation of ROS and repressed activity
      of pathogenesis-related proteins such as peroxidases, chitinase and phenylalanine
      ammonia lyase compared to their temperate counterparts. These findings bring
      insights into a hidden pathogenic characteristic of tropical D. rosae field
      isolates compared to their temperate counterparts and open a novel dimension of
      parameters to be considered when controlling black spot disease of roses by
      fungicides in tropical versus temperate regions. Interestingly, we found that
      treatment of rose leaves with ROS (H2O2) prior to fungal inoculation promoted
      plant defense response regardless of the isolate virulence based on protein
      expression pattern analysis, suggesting that ROS (H2O2) can be efficiently
      incorporated into black spot disease management.

PMID- 20137961
TI  - Coordinated transcriptional regulation of the divinyl ether biosynthetic genes in
      tobacco by signal molecules related to defense.
AB  - In tobacco, 9-divinyl ethers (DVEs) produced by the lipoxygenase NtLOX1 and DVE
      synthase NtDES1 are important for full resistance to pathogens. In this work, the
      regulation of NtLOX1 and NtDES1 expression by signal molecules was investigated
      in LOX1 promoter-reporter transgenic plants and by RT-qPCR. Methyl jasmonate, ACC
      and elicitor were shown to coordinately trigger the DVE pathway. Induction was
      strongly attenuated in the presence of salicylic acid, which seems to act as a
      negative regulator of the 9-DVE biosynthetic enzymes. Our data suggest that, in
      tobacco, DVE biosynthesis is cross-regulated by jasmonates, and by other hormonal
      and signal molecules such as ethylene and SA.

PMID- 20137962
TI  - Quantitative analysis of plant polyamines including thermospermine during growth
      and salinity stress.
AB  - Arabidopsis thaliana was thought to contain two spermine synthase genes, ACAULIS
      5 (ACL5) and SPMS. Recent investigations, however, revealed that the ACL5 gene
      encodes thermospermine synthase. In this study, we have established a simple
      method to separate two isomers of tetraamine, spermine and thermospermine, in
      extracts from plant tissues of less than 500 mg. Polyamines (PAs) extracted from
      plant tissues were benzoylated, and the derivatives were completely resolved by
      high-performance liquid chromatography on a C18 reverse-phase column, by eluting
      with 42% (v/v) acetonitrile in water in an isocratic manner at 30 degrees C and
      monitoring at 254 nm. The relevance of the method was confirmed by co
      chromatography with respective PAs and by the PA analysis of the single- and
      double-mutants of acl5 and spms, which could not synthesize thermospermine and/or
      spermine, respectively. Furthermore, with this method, we monitored the
      thermospermine contents in various tissues of A. thaliana and found that stems
      and flowers contain two- to three-fold more thermospermine compared to whole
      seedlings and mature leaves. The presence of thermospermine was confirmed in
      Oryza sativa and Lycopersicon pesculentum. Finally we addressed whether salinity
      stress changes the contents of PAs including thermospermine in Arabidopsis.

PMID- 20137963
TI  - Heat causes oligomeric disassembly and increases the chaperone activity of small
      heat shock proteins from sugarcane.
AB  - Small heat shock proteins (sHsp) constitute an important chaperone family linked
      to conformational diseases. In plants, sHsps prevent protein aggregation by
      acting as thermosensors and to enhance cell stress tolerance. SsHsp17.2 and
      SsHsp17.9 are the most highly expressed class I sHsps in sugarcane. They exist as
      dodecamers at 20 degrees C and have distinct substrate specificities. Therefore,
      they are useful models to study how class I SHsps work. Here we present data on
      the effects of heat on the oligomerization and chaperone activity of SsHsp17.2
      and SsHsp17.9. Using several biophysical and biochemical probes, we show that the
      effects of heat are completely reversible, an important property for proteins
      that act at heat shock temperatures. SsHsp17.2 and SsHsp17.9 dodecamers
      dissociated to dimers at temperatures ranging from 40 to 45 degrees C and this
      dissociation was followed by enhanced chaperone activity. We conclude that high
      temperature affects the oligomeric state of these chaperones, resulting in
      enhanced chaperone activity.

PMID- 20137964
TI  - Role of polyamines in plant vascular development.
AB  - Several pieces of evidence suggest a role for polyamines in the regulation of
      plant vascular development. For instance, polyamine oxidase gene expression has
      been shown to be associated with lignification, and downregulation of S
      adenosylmethionine decarboxylase causes dwarfism and enlargement of the
      vasculature. Recent evidence from Arabidopsis thaliana also suggests that the
      active polyamine in the regulation of vascular development is the tetraamine
      thermospermine. Thermospermine biosynthesis is catalyzed by the aminopropyl
      transferase encoded by ACAULIS5, which is specifically expressed in xylem vessel
      elements. Both genetic and molecular evidence support a fundamental role for
      thermospermine in preventing premature maturation and death of the xylem vessel
      elements. This safeguard action of thermospermine has significant impact on xylem
      cell morphology, cell wall patterning and cell death as well as on plant growth
      in general. This manuscript reviews recent reports on polyamine function and
      places polyamines in the context of the known regulatory mechanisms that govern
      vascular development.

PMID- 20137965
TI  - Congenital heart disease: interrelation between German diagnosis-related groups
      system and Aristotle complexity score.
AB  - OBJECTIVES: The Disease-Related Groups (DRGs) system postulates that inpatient
      stays with similar levels of clinical complexity are expected to consume similar
      amounts of resources. This, applied to surgery of congenital heart disease,
      suggests that the higher the complexity of procedures as estimated by the
      Aristotle complexity score, the higher hospital reimbursement should be. This
      study analyses how much case-mix index (CMI) generated by German DRG 2009 version
      correlates with Aristotle score. METHODS: A total of 456 DRG cases of year 2008
      were regrouped according to German DRG 2009 and related cost-weight values and
      overall CMI evaluated. Corresponding Aristotle basic and comprehensive complexity
      scores (ABC and ACC) and levels were determined. Associated surgical performance
      (Aristotle score times hospital survival) was estimated. Spearman 'r' correlation
      coefficients were calculated between Aristotle scores and cost-weights. Goodness
      of fit 'r(2)' from derived regression was determined. Correlation was estimated
      to be optimal if Spearman 'r' and derived goodness of fit 'r(2)' approached 1
      value. RESULTS: CMI was 8.787 while mean ABC and ACC scores were 7.64 and 9.27,
      respectively. Hospital survival was 98.5%: therefore, surgical performance
      attained 7.53 (ABC score) and 9.13 (ACC score). ABC and ACC scores and levels
      positively correlated with cost-weights. With Spearman 'r' of 1 and goodness of
      fit 'r(2)' of 0.9790, scores of the six ACC levels correlated at best. The
      equation was y = 0.5591 + 0.939x, in which y stands for cost-weight (CMI) and x
      for score of ACC level. CONCLUSIONS: ACC score correlates almost perfectly with
      corresponding cost-weights (CMI) generated by the German DRG 2009. It could
      therefore be used as the basis for hospital reimbursement to compensate in
      conformity with procedures' complexity. Extrapolated CMI in this series would be
      9.264. Modulation of reimbursement according to surgical performance could be
      established and thus 'reward' quality in congenital heart surgery.

PMID- 20137966
TI  - Long-term results after correction of persistent truncus arteriosus in 83
      patients.
AB  - OBJECTIVE: This study aims to analyse long-term results after correction of
      truncus arteriosus in all patients operated in one institution over 28 years.
      METHODS: Between 1981 and 2009, 83 patients, median age 54 days, underwent repair
      of truncus arteriosus. Interrupted aortic arch was present in 14 (17%), severe
      truncal valve insufficiency in 10 (12%) and non-confluent pulmonary arteries in
      five (6%) patients. Repair with reconstruction of the right ventricular to
      pulmonary artery continuity was performed using a valved conduit in 80, and other
      methods in three patients. At the same time, correction of interrupted aortic
      arch was done in 14 and truncal valve repair in eight patients. Survivors were
      repeatedly examined echocardiographically for assessment of residual heart
      lesions. RESULTS: The early mortality was 19 (23%). Out of 35 patients operated
      between 1981 and 1996, 17 (46%) died, and out of 48 patients operated between
      1997 and 2009, two (4%) died. Operation before 1997 (p=0.001) and aortic cross
      clamping time >90min (p=0.009) were found to be risk factors of death. Eight
      (10%) patients died late, a median of 68 days after surgery. Fifty-seven (69%)
      patients were followed for 10.9 + or - 6.7 years. Three (4%) patients were lost.
      Twenty-five (30%) patients are alive with their original conduit 7.5 + or - 5.2
      years after correction. Twenty-eight patients required 41 re-operations for
      conduit dysfunction with first replacement at mean 5.8 + or - 4.1 (range 0.1-14.1
      years) years after correction. Nine (11%) patients required 12 truncal valve
      replacements. Eleven (13%) patients required balloon dilatation or stent for
      conduit obstruction, pulmonary branch stenosis, aortic arch obstruction or
      stenosis of vena cava. Recent clinical examination was undertaken in 53 (64%)
      patients and 49 (59% or 77% of early survivors) are in good/very good condition.
      CONCLUSIONS: Truncus arteriosus remains a challenging heart disease. With growing
      experience, the early mortality decreased to 4%, but numerous re-interventions
      for conduit obstruction, pulmonary branch stenosis and truncal valve
      insufficiency are required. Surgery before 1997 and prolonged cross-clamping were
      risk factors of death. Pulmonary homografts had the best re-intervention-free
      survival. Statistically, however, the difference between conduits was not
      significant. Dysplastic valve and truncal valve insufficiency represent risk
      factors presenting the need for truncal valve replacement.

PMID- 20137967
TI  - Clinical outcome of resected solid-type small-sized c-stage IA non-small cell
      lung cancer.
AB  - BACKGROUND: The chances of pulmonary resection for small-sized lung cancer have
      increased because of the development of thin-slice computed tomography (CT).
      Though sublobar resection could be indicated for ground glass opacity (GGO)
      dominant adenocarcinoma with low-grade behaviour, the malignant potential of
      solid-type, small-sized lung cancer has not been sufficiently assessed. We aimed
      to address the clinical outcomes of resected solid-type c-stage IA non-small cell
      lung cancer (NSCLC) smaller than 2 cm. METHODS: A retrospective observational
      study involving 118 patients who had undergone a complete resection for lung
      cancer smaller than 2 cm with solid component more than 50% on CT was conducted,
      and their postoperative survival and recurrence pattern were analysed. RESULTS:
      Thirty-five patients with solid component-dominant lesion (SCDL) and 83 patients
      with pure solid lesion (PSL) without GGO were enrolled. Lymph node involvement
      was found in 15 patients with PSL (18%). The 5-year disease-free survival (DFS)
      was 100% in SDCL patients and 83% in PSL patients. Multivariate analysis of PSL
      patients showed that lymph node metastasis and pleural invasion were independent
      negative prognostic predictors. The 5-year DFS was 88%, 80% and 46% in p-N0, p-N1
      and p-N2 patients, respectively. The 5-year DFS was 33% for patients with pleural
      invasion, which was significantly worse than that for patients without pleural
      involvement. Postoperative recurrence was mainly observed as intrathoracic
      lesions within 3 years. CONCLUSIONS: A proportion of solid-type NSCLC has
      malignant potential, even for tumours smaller than 2 cm. Periodic intrathoracic
      evaluation is required following complete resection.

PMID- 20137968
TI  - Massive air embolism during coronary multislice spiral computed tomography.

PMID- 20137969
TI  - A phase I study of adoptive immunotherapy for recurrent non-small-cell lung
      cancer patients with autologous gammadelta T cells.
AB  - OBJECTIVES: Human gammadelta T lymphocytes can recognise and kill non-small-cell
      lung cancer cells by Vgamma9Vdelta2 T-cell receptor and/or NKG2D. We have
      established large-scale ex vivo expansion of gammadelta T cells by zoledronate
      and interleukin-2. This pilot feasibility study evaluates the safety and
      potential anti-tumour effects of activated autologous gammadelta T cells
      administered intravenously to patients. METHODS: Patients who had measurable foci
      of recurrent non-small-cell lung cancer were registered to undergo gammadelta T
      cell immunotherapy, designed as a one-way, open, clinical research, after their
      informed consent. Mononuclear cells collected from peripheral blood of the
      patient were cultured with zoledronic acid and interleukin-2. After 2-week
      incubation, the gammadelta T-cell fraction was proliferated and it was
      intravenously reinfused to the patient. RESULTS: Ten patients had undergone the
      gammadelta T-cell immunotherapy. They were administered autologous gammadelta T
      cells 3-12 times (mean=6) every 2 weeks. No patient died during the study period.
      Adverse events, not directly related to the immunotherapy, were observed five
      times in four patients (grade 3 pneumonia in two and grade 1 coldness in three).
      According to the Response Evaluation Criteria in Solid Tumours, neither complete
      nor partial response was achieved in any patient; stable disease was observed in
      three; and progressive disease in five at 4 weeks after six consecutive
      injections of during immunotherapy. The Functional Assessment of Cancer Therapy
      Biologic Response Modifier scores of the patients during immunotherapy were
      stable or improved, except for one patient who had suffered from pneumonia. The
      patients were followed up after immunotherapy for 240-850 days (median=401 days).
      At the end of the observation, six patients were alive. CONCLUSIONS: We suggest
      that gammadelta T-cell immunotherapy might be safe and feasible for patients with
      recurrent non-small-cell lung cancer.

PMID- 20137970
TI  - Editorial comment.

PMID- 20137971
TI  - Novel epicardial off-pump device for mitral regurgitation: acute evaluation.
AB  - OBJECTIVE: This study evaluates the ability of a novel epicardial annuloplasty
      device Mitral Touch (MAQUET Cardiovascular LLC, San Jose, CA, USA) to reduce
      functional mitral regurgitation (MR) in a rapid ventricular pacing-induced
      dilated cardiomyopathy model in dogs. METHODS: A median sternotomy was performed
      in 13 dogs after MR induction by rapid ventricular pacing (230 beats/min for an
      average of 35.6 + or - 12.8 days). Two-dimensional epicardial echocardiographic
      and haemodynamic measurements were performed to evaluate the baseline MR grade,
      the septal-lateral (S-L) dimension of the mitral annulus, mitral valve (MV)
      geometry and left ventricular function. The Mitral Touch was implanted by sliding
      the anterior arm onto the floor of the transverse sinus and positioning the
      posterior arm just apical to the atrioventricular groove on the left ventricular
      posterolateral wall. The 24-mm-long device was implanted in eight dogs, the 27-mm
      long device in four and the 30-mm standard length device in one. MR grade, S-L
      dimension and haemodynamics data acquisition were immediately rechecked after
      device implantation. RESULTS: All implantations, which took only approximately
      30s to deploy, were performed on beating hearts without cardiopulmonary bypass.
      In one early case, after extended manipulation with undersized devices, an atrial
      laceration was created and bleeding occurred. Design changes were made to
      eliminate this complication. The MR grade was significantly (p=0.003) reduced
      from 3.1 + or - 1.1 at baseline to 1.4 + or - 0.8 after device implantation. The
      S-L dimension at end of systole was also significantly (p=0.001) reduced from 2.7
      + or - 0.4 cm at baseline to 2.3 + or - 0.3 cm after device implantation (%
      reduction: 15.1 + or - 10.6%). The mitral valve coaptation length was
      significantly (p=0.0001) increased from 0.36 + or - 0.11 cm to 0.50 + or - 0.08
      cm, and the mitral valve tethering area was significantly (p=0.0003) decreased
      from 1.36 + or - 0.38 cm(2) to 0.81 + or - 0.29 cm(2) after Mitral Touch
      implantation. CONCLUSIONS: This new epicardial device was effective in
      significantly reducing MR and S-L dimensions acutely on the beating heart without
      requiring the use of cardiopulmonary bypass. Further studies are necessary to
      confirm the long-term maintenance of MR and S-L reductions.

PMID- 20137972
TI  - The fate of the aortic root after early repair of tetralogy of Fallot.
AB  - OBJECTIVE: Late aortic root dilatation is a growing concern in patients operated
      on for tetralogy of Fallot (ToF). This longitudinal follow-up study sought to
      evaluate the changes in the aortic root dimensions in relation to body growth,
      assuming that early repair of tetralogy of Fallot might prevent late aortic
      dilatation. METHODS: A retrospective analysis of the aortic root dimensions was
      performed in 88 patients repaired early for tetralogy of Fallot by
      echocardiographic measurement of aortic annulus, sinus of Valsalva and
      sinotubular junction, adjusted for body surface area and expressed as z-scores.
      Mean age at repair was 9.7 + or - 7.4 months. Median age was 7.3 months (range 45
      days-29 months). RESULTS: At the time of repair, all root dimensions were
      enlarged: z-score of the annulus 3.32 + or - 1.66; sinus 3.54 + or - 1.49;
      sinotubular junction 2.74 + or - 1.19. Within a mean follow-up of 6.9 + or - 4.4
      years, the mean z-scores of both annulus and sinotubular junction significantly
      decreased to normal size at 7 years postoperatively: z-score of annulus 0.95 + or
      - 0.7 (p=0.006), z-score of sinotubular junction 0.99 + or - 1.47 (p=0.006). The
      z-score of the aortic sinuses appeared to regress slower to 2.78 + or - 1.26
      (p=0.262). The indexed sinus diameter however regressed significantly from a mean
      of 51.4 + or - 13.4 mmm(-2) at correction to 28.9 + or - 7.2 mmm(-2) (p=0.0001)
      at latest follow-up. Evolution of aortic root size after repair was independent
      of aortic arch side, sex, age at repair or previous shunt palliation.
      CONCLUSIONS: The initially dilated aortic root in tetralogy of Fallot normalises
      in size at the level of the annulus and sinotubular junction within 7 years after
      early repair. This process seems delayed at the level of the aortic sinuses,
      although the indexed root diameter shows significant regression over time. These
      results suggest that early repair of ToF abrogates the enlargement of the aortic
      root, validating one aspect of the need for tetralogy correction at a young age.

PMID- 20137973
TI  - Improving availability and affordability of plasma-derived medicines.
AB  - Plasma contains several therapeutically important proteins. Currently more than
      25 of them are commercially available to treat life-threatening diseases. Some of
      these medicines already included in the WHO Model List of Essential Medicines
      indicating their importance from a global perspective. However, unfortunately due
      to very high cost of treatment with plasma-derived medicines, these clinically
      precious tools are not affordable for a majority of the patients living in
      developing countries. There are some options available for securing accessibility
      to these medicines. These include local production, importation and contract
      fractionation of locally produced plasma. Although local production of plasma
      derived medicines and/or importation of these medicines might be a practical
      approach to respond to the needs for these medicines, in recent years several
      countries have used contract fractionation of locally produced plasma as a very
      effective approach for improving availability and affordability of plasma-derived
      medicines in their national market.

PMID- 20137974
TI  - Total cost and operating room time comparison of rotator cuff repair techniques
      at low, intermediate, and high volume centers: mini-open versus all-arthroscopic.
AB  - BACKGROUND: The objective of this study was to determine mean cost and operative
      time differences between mini-open and all-arthroscopic rotator cuff repair
      techniques at surgical centers of low, intermediate, and high annual rotator cuff
      repair volume. METHODS: The 2006 New York State Ambulatory Surgery Database (NY
      SASD) was utilized. It represents 100% of all outpatient procedures performed in
      hospital-affiliated and freestanding surgical centers, containing 10,658,923
      patients for 2006 alone. Only patients who had an arthroscopic acromioplasty and
      either open or arthroscopic rotator cuff repair were included, leaving 5,224
      patients for the study. These were divided into 2 groups: the mini-open group
      (1,334) and the all-arthroscopic group (3,890). Surgical center volume data were
      divided into 3 groups: low volume (<75 rotator cuff repairs per year),
      intermediate volume (75-199 rotator cuff repairs per year), and high volume (200+
      rotator cuff repairs per year). RESULTS: Patient age and gender were normally
      distributed within the 2 groups with no significant differences between them (P =
      .82 and P = .31, respectively). Operative time was significantly shorter in the
      mini-open group (103 minutes) compared to the all-arthroscopic group (113
      minutes), P < .00001. Surgical charges were also significantly less in the mini
      open group ($7,841) compared to the all-arthroscopic group ($8,985), P < .00001.
      Regardless of the repair method, high volume surgical centers were significantly
      more expensive when compared to low and intermediate volume centers, P < .00001.
      CONCLUSION: The mini-open rotator cuff repair technique requires significantly
      less operative time and is significantly less expensive than the all-arthroscopic
      repair. Regardless of the repair technique, high volume surgical centers cost
      significantly more than low and intermediate volume surgical centers.

PMID- 20137975
TI  - Image-based navigation improves the positioning of the humeral component in total
      elbow arthroplasty.
AB  - HYPOTHESIS: Implant alignment in total elbow arthroplasty (TEA) is a challenging
      and error-prone process using conventional techniques. Identification of the
      flexion-extension (FE) axis is further complicated for situations of bone loss.
      This study evaluated the accuracy of humeral component alignment in TEA. We
      hypothesized that an image-based navigation system would improve humeral
      component positioning, with navigational errors less than or approaching 2.0 mm
      and 2.0 degrees . MATERIALS AND METHODS: Implantation of a modified commercial
      TEA humeral component was performed with and without navigation on 11 cadaveric
      distal humeri. Navigated alignment was based on positioning the humeral component
      with the aid of a computed tomography (CT)-based preoperative plan registered to
      landmarks on the distal humerus. Alignment was performed under 2 scenarios of
      bone quality: (1) an intact distal humerus, and (2) a distal humerus without
      articular landmarks. RESULTS: Navigation significantly improved implant alignment
      accuracy (P < .001). Navigated implant alignment was 1.2 +/- 0.3 mm in
      translation and 1.3 degrees +/- 0.3 degrees in rotation for the intact scenario.
      For the bone loss scenario, navigated alignment error was 1.1 +/- 0.5 mm and 2.0
      degrees +/- 1.3 degrees . Non-navigated alignment was 3.1 +/- 1.3 mm and 5.0
      degrees +/- 3.8 degrees for the intact scenario and 3.0 +/- 1.6 mm and 12.2
      degrees +/- 3.3 degrees for the bone loss scenario. DISCUSSION: Image-based
      navigation improves the accuracy and reproducibility of humeral component
      placement in TEA. Implant alignment errors for the navigated alignments were
      below the target of 2.0 degrees and 2 mm that is considered standard for most
      navigation systems. Non-navigated implant alignment error was significantly
      greater for the bone loss scenario compared with the intact scenario.
      CONCLUSIONS: Implant malalignment may increase the likelihood of early implant
      wear, instability, and loosening. Improved implant positioning will likely lead
      to fewer complications and greater prosthesis longevity.

PMID- 20137976
TI  - Can shoulder arthroplasty restore the range of motion in activities of daily
      living? A prospective 3D video motion analysis study.
AB  - HYPOTHESIS: There are limited data how total shoulder arthroplasty (TSA) improves
      shoulder function during activities of daily living (ADL). The hypothesis of this
      study was that the range of motion (ROM) in ADL gets back to normal after TSA.
      MATERIALS AND METHOD: We examined 13 patients before they received TSA for
      osteoarthritis and 6 months postoperatively with a 3D motion video analysis
      during 3 ADL and compared them with a control group without any shoulder
      pathology. RESULT: Comparing the TSA status preoperatively and postoperatively
      resulted in a significant increase of the mean values of the ROMs in the ADL in
      all planes (P < .05). When the postoperative ROM was compared with the controls,
      TSA was able to restore the ROM in all planes except for abduction in 2 of 3 ADL.
      The patients were not able to use their maximum active abduction during the
      course of the ADL. DISCUSSION: TSA improves the ROM in ADL, but it cannot return
      completely to normal in abduction after 6 months. CONCLUSION: This is not related
      to limitations of active or passive ROM but may be due to impaired proprioception
      or pathologic movement patterns, or both.

PMID- 20137977
TI  - Management of chronic shoulder infections utilizing a fixed articulating
      antibiotic-loaded spacer.
AB  - BACKGROUND: Literature on management of chronic shoulder infections is limited.
      The purpose of this study was to examine the efficacy of a standardized protocol
      for the management of chronic shoulder infections, including periprosthetic
      infections, utilizing an articulating antibiotic-loaded spacer. MATERIAL AND
      METHODS: Thirty patients with chronic shoulder infections (4 primary and 26
      postoperative) were treated with aggressive debridement, implantation of an
      antibiotic-loaded articulating spacer, and systemic antibiotics. Twenty-seven
      patients (90%) were compromised hosts. Eighteen patients (group I) elected to
      keep the spacer but three patients later underwent reimplantation, thus fifteen
      patients (group IA) were using the spacer as a prosthesis at their latest follow
      up of 2.4 years. Twelve patients (group II, follow-up of 2.3 years) underwent
      reimplantation of a prosthesis. RESULTS: Eradication of infection was
      accomplished in all 30 patients. Group IA patients had a Disability of Arm
      Shoulder and Hand (DASH) score of 50, Simple Shoulder Test (SST) score of 5,
      forward flexion of 73 degrees, abduction of 71 degrees, and external rotation of
      29 degrees. Group II patients had a DASH score of 58, SST score of 5, forward
      flexion of 78 degrees, abduction of 83 degrees, and external rotation of 19
      degrees. The differences between these 2 groups were not significant. DISCUSSION:
      Chronic shoulder infections can be successfully treated with a protocol of
      aggressive debridement, antibiotic-loaded articulating spacer, and systemic
      antibiotics. Prolonged implantation of an articulating spacer may be a viable
      option in select low-demand patients with comorbidities.

PMID- 20137978
TI  - Reliability of the glenoid plane.
AB  - HYPOTHESIS: The purpose of this study was to investigate the 3-dimensional (3-D)
      orientation of the glenoid and scapular planes. Different definitions of the
      glenoid plane were used and different planes measured, and we hypothesed that the
      3-D plane with the least variation would be best to define the most reliable
      glenoid plane. METHODS: We studied 150 CT scans from nonpathological shoulders
      from patients between 18 and 80. The scapular plane and 5 different glenoid
      planes were determined: inferior, anterior, posterior, superior, and neutral. All
      plane versions and inclination angles were measured. Because all examinations
      were done in a standardized position to the coronal, sagittal, and transverse
      planes of the body, the scapular plane could be defined versus the coronal,
      sagittal, and transverse planes of the body. RESULTS: The version (mean, 3.76) of
      the inferior glenoid plane showed a significantly lower standard deviation than
      the version of the anterior (P < .001), posterior (P=.001), and superior (P=.001)
      glenoid plane (ANOVA). For inclination all planes have a similar variance. The
      scapular plane was different between gender (P=.022) and correlated with age.
      CONCLUSION: This study showed that the retroversion of the inferior glenoid is
      reasonably constant. The osseous anthropometry of the inferior glenoid can offer
      a reproducible point of reference to be used in prosthetic surgery of the
      shoulder.

PMID- 20137979
TI  - Acute ischemia of the hand seven months after tension-band wiring of the
      olecranon.

PMID- 20137980
TI  - Comparison of Achilles tendon repair techniques in a sheep model using a cross
      linked acellular porcine dermal patch and platelet-rich plasma fibrin matrix for
      augmentation.
AB  - The primary goal of this study was to evaluate a cross-linked acellular porcine
      dermal patch (APD), as well as platelet-rich plasma fibrin matrix (PRPFM), for
      repair of acute Achilles tendon rupture in a sheep model. The 2 surgically
      transected tendon ends were reapproximated in groups 1 and 2, whereas a gap was
      left between the tendon ends in group 3. APD was used to reinforce the repair in
      group 2, and autologous PRPFM was used to fill the gap, which was also reinforced
      with APD, in group 3. All sheep were humanely euthanized at 24 weeks after the
      repair, and biomechanical and histological testing were performed. Tensile
      strength testing showed a statistically significant difference in elongation
      between the operated limb and the unoperated contralateral limb in groups 1 and
      3, but not in group 2. All operated tendons appeared healed with no apparent
      fibrosis under light and polarized microscopy. In group 1, all surgical
      separation sites were identifiable, and healing occurred via increasing tendon
      thickness. In group 2, healing occurred with new tendon fibers across the
      separation, without increasing tendon thickness in 2 out of 6 animals. Group 3
      showed complete bridging of the gap, with no change in tendon thickness in 2 out
      of 6 animals. In groups 2 and 3, peripheral integration of the APD to tendon
      fibers was observed. These findings support the use of APD, alone or with PRPFM,
      to augment Achilles tendon repair in a sheep model.

PMID- 20137982
TI  - Gastrocnemius recession as an alternative to tendoAchillis lengthening for relief
      of forefoot pressure in a patient with peripheral neuropathy: a case report and
      description of a technical modification.
AB  - The gastrocnemius recession is a popular surgical procedure for the treatment of
      equinus contracture. Lengthening the gastrocnemius tendon has been show to be an
      effective means of reducing pressure to the plantar forefoot by weakening the
      triceps surae complex. The more traditional method of weakening the triceps surae
      is a modification of Hoke's triple hemisection through the tendoAchillis. This
      technique unfortunately carries a serious risk of the development of a calcaneal
      gait. The purpose of this case report is to demonstrate that the gastrocnemius
      recession is an effective and safe alternative to the traditional tendoAchillis
      lengthening. The authors also describe a minimally invasive technique that uses a
      pediatric speculum for a self-retrained retractor and portal for instrumentation
      and visualization.

PMID- 20137983
TI  - Functional outcome and patient satisfaction after flexor tenotomy for plantar
      ulcers of the toes.
AB  - Ulcers of the toes may cause a severe physical burden, especially in patients
      with diabetes, in whom they occur most frequently. Several treatments have been
      proposed for the underlying anatomical abnormalities, but they vary in
      effectiveness. We evaluated our results in using flexor tenotomy to treat ulcers
      with underlying flexible clawing of the toes. For 42 toes from 23 patients, 15 of
      whom were diabetic, all ulcers healed. The mean healing time was 4 weeks (range,
      1-8 weeks), the mean follow-up was 11 months (range, 1-27 months), and one
      recurrence and one complication occurred. Postoperative American Orthopaedic Foot
      Ankle Society Midfoot scores were available for 15 patients: the mean was 77
      (range, 43-100). The mean visual analogue scale (VAS) for patient satisfaction
      increased from 3.9 points (range, 0-10 points) preoperatively to 7.7 (range, 5-10
      points) postoperatively. Flexor tenotomy is a simple treatment with low
      complications and recurrence rates and provides good-to-excellent functional
      outcomes in treating flexible clawing of the toes and the associated ulceration.

PMID- 20137984
TI  - Safety of local anesthesia combined with monitored intravenous sedation for
      American Society of Anesthesiologists 3 and 4 patients undergoing lower limb
      preservation procedures.
AB  - The aim of this retrospective study is to evaluate the prognostic value of
      American Society of Anesthesiologists (ASA) classification with regard to
      perioperative variables of cardiac complications, pulmonary complications, and
      mortality in patients undergoing limb salvage procedures with monitored
      intravenous sedation and foot and ankle blocks. None of the ASA 3 or 4 patients
      experienced any pulmonary or cardiac complication; no patient required invasive
      monitoring or postoperative cardiac care unit admission. We suggest that the
      performance of peripheral foot and ankle blocks with monitored intravenous
      sedation appears to be a safe and useful option for ASA 3 and 4 patients
      undergoing limb-preservation surgery.

PMID- 20137985
TI  - Foxp3+ T cells induce perforin-dependent dendritic cell death in tumor-draining
      lymph nodes.
AB  - Regulatory T (Treg) cells limit the onset of effective antitumor immunity,
      through yet-ill-defined mechanisms. We showed the rejection of established
      ovalbumin (OVA)-expressing MCA101 tumors required both the adoptive transfer of
      OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the
      neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T
      cell neutralization induced a marked arrest in the migration of OTI T cells,
      increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming.
      Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive
      transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs
      in tumor-draining lymph nodes, but not in the absence of tumor. DC death
      correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and
      perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor
      draining lymph nodes limits the onset of CD8(+) T cell responses.

PMID- 20137986
TI  - T cell receptor-dependent regulation of lipid rafts controls naive CD8+ T cell
      homeostasis.
AB  - T cell receptor (TCR) contact with self ligands keeps T cells alive and is shown
      here to cause naive CD8(+), but not CD4(+), T cells to be hypersensitive to
      certain gamma(c) cytokines, notably interleukin (IL)-2, IL-15, and IL-7.
      Hypersensitivity of CD8(+) T cells to IL-2 was dependent on a low-level TCR
      signal, associated with high expression of CD5 and GM1, a marker for lipid rafts,
      and was abolished by disruption of lipid rafts. By contrast, CD4(+) T cells
      expressed low amounts of GM1 and were unresponsive to IL-2. Physiologically,
      sensitivity to IL-7 and IL-15 maintains survival of resting CD8(+) T cells,
      whereas sensitivity to IL-2 may be irrelevant for normal homeostasis but crucial
      for the immune response. Thus, TCR contact with antigen upregulates GM1 and
      amplifies responsiveness of naive CD8(+) T cells to IL-2, thereby making the
      cells highly sensitive to exogenous IL-2 from CD4(+) T helper cells.

PMID- 20137987
TI  - Dependence of T cell antigen recognition on T cell receptor-peptide MHC
      confinement time.
AB  - T cell receptor (TCR) binding to diverse peptide-major histocompatibility complex
      (pMHC) ligands results in various degrees of T cell activation. Here we analyze
      which binding properties of the TCR-pMHC interaction are responsible for this
      variation in pMHC activation potency. We have analyzed activation of the 1G4
      cytotoxic T lymphocyte clone by cognate pMHC variants and performed thorough
      correlation analysis of T cell activation with 1G4 TCR-pMHC binding properties
      measured in solution. We found that both the on rate (k(on)) and off rate
      (k(off)) contribute to activation potency. Based on our results, we propose a
      model in which rapid TCR rebinding to the same pMHC after chemical dissociation
      increases the effective half-life or "confinement time" of a TCR-pMHC
      interaction. This confinement time model clarifies the role of k(on) in T cell
      activation and reconciles apparently contradictory reports on the role of TCR
      pMHC binding kinetics and affinity in T cell activation.

PMID- 20137988
TI  - Comment on: "A 15-year experience with combined vascular reconstruction and free
      flap transfer for limb-salvage", C. Randon, B. Jacobs, F. De Ryck, K. Van
      Landuyt, F. Vermassen Eur. J Vasc Endovasc Surg 2009;38(3):338-345.

PMID- 20137989
TI  - Sleep and emotions: a focus on insomnia.
AB  - Insomnia disorder is defined as difficulties in initiating/maintaining sleep
      and/or non-restorative sleep accompanied by decreased daytime functioning,
      persisting for at least four weeks. For many patients suffering from depression
      and anxiety, insomnia is a pervasive problem. Many of the aetiological theories
      of insomnia postulate that heightened emotional reactivity contributes to the
      maintenance of symptoms. This review focuses on the role of emotional reactivity
      in insomnia, and how the relationship between insomnia and depression and anxiety
      may be mediated by emotional reactivity. Furthermore, studies investigating the
      valence of emotions in insomnia are reviewed. Overall, there is empirical
      evidence that dysfunctional emotional reactivity might mediate the interaction
      between cognitive and autonomic hyperarousal, thus contributing to the
      maintenance of insomnia. Moreover, dysfunctions in sleep-wake regulating neural
      circuitries seem to be able to reinforce emotional disturbances. It seems
      plausible that dysfunctional emotional reactivity modulates the relationship
      between insomnia and depression and anxiety. Considering the interaction between
      sleep and emotional valence, poor sleep quality seems to correlate with high
      negative and low positive emotions, both in clinical and subclinical samples.
      Good sleep seems to be associated with high positive emotions, but not
      necessarily with low negative emotions. This review underlines the need for
      future research on emotions in insomnia.

PMID- 20137990
TI  - Virtual screening and selection of drug-like compounds to block noggin
      interaction with bone morphogenetic proteins.
AB  - Noggin is a major natural extracellular antagonist to bone morphogenetic proteins
      (BMPs) which binds to BMPs and blocks binding of them to BMP-specific receptors
      and thus negatively regulates BMP-induced osteoblastic differentiation. Bone
      morphogenetic proteins (BMPs) signal through heteromeric protein complexes
      composed of type I and type II serine/threonine kinase receptors. Preventing the
      BMP-2/noggin interaction will preserve free BMP-2 and enhance the efficacy of BMP
      2 to induce bone formation. This work is an attempt to use the current
      understanding of BMP-2, and its interaction with its receptors and antagonist to
      design an inhibitor of BMP-2/noggin interaction with the goal of lowering the
      dose of BMP-2 required in clinical applications. The crystal structure of the BMP
      7/noggin complex, the BMP-2/BMP receptor IA ectodomain complex and the
      extracellular domain of BMP receptor II monomer are known. We modeled the BMP-2
      based on the structure of its homologue BMP-7 and its binding complex with
      noggin. We also modeled a complex of BMP-2/BMPRIA/BMPRII by modeling BMPRII and
      replacing ActRIIB in the BMP-2/BMPRIA/ActRIIB complex. We then identified the
      binding region of noggin with BMP-2 and the receptors with BMP-2. From the
      analysis of structures of these complexes and modeling we identified the key
      amino acids present in the entire interacting surfaces among these proteins that
      play important physiological role in the regulation of cell differentiation and
      bone metabolism. By in silico screening we selected and ranked several compounds
      that have high theoretical scores to bind to noggin to block BMP-noggin
      interaction.

PMID- 20137991
TI  - Maternal and congenital syphilis in Shanghai, China, 2002 to 2006.
AB  - OBJECTIVE: To assess the trends and determinants of maternal and congenital
      syphilis in Shanghai, China. METHODS: We conducted a prospective cohort study of
      maternal and congenital syphilis from 2002 to 2006 in Shanghai, China. We
      presented the trends of maternal syphilis and congenital syphilis rates and
      compared outcomes in infants born to mothers with complete versus incomplete
      treatment for maternal syphilis. We also assessed the determinants of compliance
      to treatment of maternal syphilis and examined the associations of initial
      maternal RPR antibody level and gestational age at initiation of treatment with
      occurrence of congenital syphilis. RESULTS: A total of 535 537 pregnant women
      were included in the analysis. During this period of time, 1471 maternal syphilis
      cases (298.7 per 100 000 live births) and 334 congenital syphilis cases (62.4 per
      100 000 live births) were identified. Both maternal and congenital syphilis rates
      increased from 2002 until 2005, with a slight decrease in 2006. The rate of
      maternal syphilis was 156.2 per 100 000 live births in Shanghai residents and
      371.7 per 100 000 live births in the migrating population (p<0.001). The
      compliance to treatment for maternal syphilis was poorer in women with a lower
      level of education. The rate of congenital syphilis in infants born to mothers
      with incomplete treatment (50.8%) was much higher than in infants born to mothers
      with complete treatment (12.5%). Rates of fetal death, neonatal death, and major
      birth defects were 30.4%, 11.0%, and 3.8%, respectively, in the incomplete
      treatment group; the corresponding figures were 5.5%, 0.56%, and 0.46%,
      respectively, in the complete treatment group. Infant outcome was also affected
      by initial maternal RPR antibody level and time of treatment, with much better
      outcomes in mothers with low antibody levels and earlier treatment. CONCLUSION:
      There has been a resurgence of congenital syphilis in Shanghai, China, especially
      in the migrating population and other populations with a lower socioeconomic
      status.

PMID- 20137992
TI  - Bacteremia caused by a highly-resistant Streptococcus pneumoniae serotype 19A
      circulating in a daycare center.
AB  - We describe the clinical course of a previously healthy 20-month-old toddler
      admitted with high fever and leukocytosis. Blood culture grew Streptococcus
      pneumoniae serotype 19A, belonging to the ST663 clone, highly resistant to
      penicillin, ceftriaxone, and erythromycin. The same clone with identical
      antibiogram was isolated from the nasopharynx of another three of the other five
      healthy children attending the same daycare center as the patient. This case
      exemplifies the potential problems posed by highly-resistant S. pneumoniae
      serotype 19A, an emerging pathogen worldwide.

PMID- 20137993
TI  - Effect of combination antiretroviral treatment on total protein and calculated
      globulin levels among HIV-infected patients.
AB  - OBJECTIVES: Hypergammaglobulinemia is one of the manifestations of B-cell
      dysfunction associated with untreated HIV infection. Globulin levels are not
      routinely measured in HIV-infected patients on treatment. The purpose of this
      study was to evaluate the effect of highly active antiretroviral therapy (HAART)
      on calculated globulin levels. METHODS: The study group consisted of 75 HIV
      infected treatment-naive patients, starting HAART, and virologically suppressed
      for >=6 months; 16 patients (21%) were HIV-HCV-co-infected. RESULTS: All patients
      experienced significant increases in CD4 cell counts at 6 and 12 months after
      HAART initiation compared to baseline (p<0.01 for all comparisons). The increase
      in CD4 cell counts was significant regardless of the HCV infection status.
      Significant increases in albumin levels (p<0.05 at 6 and 12 months), reductions
      in total protein (p<0.01 at 1 year; not significant at 6 months), and concomitant
      significant reductions in the calculated globulin levels (p<0.001 at 6 and 12
      months) after HAART initiation compared to baseline were observed for the whole
      group. However, less than half the patients achieved a normal albumin/globulin
      ratio at 1 year. HIV-monoinfected patients had significant changes in albumin,
      total protein, and calculated globulin levels. In contrast, HIV-HCV-co-infected
      patients only showed significant increases in albumin levels. CONCLUSIONS: Future
      studies to evaluate the potential use of calculated globulin levels and
      albumin/globulin ratios as readily available surrogate markers of B-cell immune
      reconstitution in HIV-monoinfected patients are warranted.

PMID- 20137994
TI  - Advanced glycation end products assessed by skin autofluorescence in type 1
      diabetics are associated with nephropathy, but not retinopathy.
AB  - AIMS: Advanced glycation end products (AGEs) are thought to play a central role
      in the pathogenesis of diabetes complications. For this reason, a non-invasive
      tool using skin autofluorescence (AF) quantification that correlates with levels
      of tissue AGEs has been developed. The present study aimed to assess whether or
      not skin AF is associated with microvascular complications in patients with type
      1 diabetes (T1D). METHODS: All consecutive patients with T1D (n=133) had three AF
      measures taken on the forearm, using illumination with a fluorescent tube, all on
      the same day after breakfast or lunch. Potential associations between skin AF
      levels and microvascular complications, age, diabetes duration and health status
      were then assessed using a multivariate linear-regression model. RESULTS: On age
      adjusted analyses, diabetes duration, retinopathy, nephropathy and neuropathy
      were significantly associated with skin AF levels (all P<0.001). AF levels
      increased significantly with severity in both retinopathy and nephropathy
      (P<0.001). After adjusting for age, diabetes duration, HbA(1c), smoking,
      retinopathy, nephropathy and neuropathy, the association of AF levels remained
      significant with nephropathy and neuropathy, but not with retinopathy and
      diabetes duration. CONCLUSION: This study suggests an independent association
      between skin AF levels and diabetic nephropathy and neuropathy, but not
      retinopathy, in T1D patients. Prospective studies are needed to confirm the
      ability of skin AF levels to predict microangiopathy.

PMID- 20137995
TI  - Re: Biomechanical study of mandible bone supporting a four-implant retained
      bridge finite element analysis of the influence of bone anisotropy and foodstuff
      position.

PMID- 20137996
TI  - Neighborhood environment and physical activity among urban and rural
      schoolchildren in Taiwan.
AB  - The purpose of this study is to investigate the influence of perceived
      neighborhood environment on physical activity among schoolchildren in urban and
      rural areas in Taiwan. Five hundred and twenty three children of grades five and
      six selected from ten primary schools in urban and rural areas participated in
      the study. A modified International Physical Activity questionnaire short form
      was used to estimate the children's physical activity level. A Chinese
      translation of the Neighborhood Environment Walkability Scale assessed
      environmental attributes. Data analysis included descriptive statistics and
      analysis of variance and multiple regression models. No significant difference in
      walkability was found between the urban and rural areas. There was a difference
      in accessibility to places for physical activity between urban and rural areas,
      with urban children reporting greater accessibility. The urban children reported
      more physical activity after school, on holidays and weekends, and also in total
      amount of physical activity compared with the rural children. In conclusion,
      accessibility to facilities had a significant impact on the children's physical
      activity.

PMID- 20137997
TI  - Induced plant volatiles: from genes to climate change.

PMID- 20137998
TI  - Automatic detection of informative frames from wireless capsule endoscopy images.
AB  - Wireless capsule endoscopy (WCE) is a new clinical technology permitting
      visualization of the small bowel, the most difficult segment of the digestive
      tract. The major drawback of this technology is the excessive amount of time
      required for video diagnosis. We therefore propose a method for generating
      smaller videos by detecting informative frames from original WCE videos. This
      method isolates useless frames that are highly contaminated by turbid fluids,
      faecal materials and/or residual foods. These materials and fluids are presented
      in a wide range of colors, from brown to yellow, and/or have bubble-like texture
      patterns. The detection scheme therefore consists of two steps: isolating (Step
      1) highly contaminated non-bubbled (HCN) frames and (Step-2) significantly
      bubbled (SB) frames. Two color representations, viz., local color moments in Ohta
      space and the HSV color histogram, are attempted to characterize HCN frames,
      which are isolated by a support vector machine (SVM) classifier in Step-1. The
      rest of the frames go to Step-2, where a Gauss Laguerre transform (GLT) based
      multiresolution texture feature is used to characterize the bubble structures in
      WCE frames. GLT uses Laguerre Gauss circular harmonic functions (LG-CHFs) to
      decompose WCE images into multiresolution components. An automatic method of
      segmentation was designed to extract bubbled regions from grayscale versions of
      the color images based on the local absolute energies of their CHF responses. The
      final informative frames were detected by using a threshold on the segmented
      regions. An automatic procedure for selecting features based on analyzing the
      consistency of the energy-contrast map is also proposed. Three experiments, two
      of which use 14,841 and 37,100 frames from three videos and the rest uses 66,582
      frames from six videos, were conducted for justifying the proposed method. The
      two combinations of the proposed color and texture features showed excellent
      average detection accuracies (86.42% and 84.45%) with the final experiment, when
      compared with the same color features followed by conventional Gabor-based
      (78.18% and 76.29%) and discrete wavelet-based (65.43% and 63.83%) texture
      features. Although intra-video training-testing cases are typical choices for
      supervised classification in Step-1, combining a suitable number of training sets
      using a subset of the input videos was shown to be possible. This mixing not only
      reduced computation costs but also produced better detection accuracies by
      minimizing visual-selection errors, especially when processing large numbers of
      WCE videos.

PMID- 20137999
TI  - Detection and use of QTL for complex traits in multiple environments.
AB  - QTL mapping methods for complex traits are challenged by new developments in
      marker technology, phenotyping platforms, and breeding methods. In meeting these
      challenges, QTL mapping approaches will need to also acknowledge the central
      roles of QTL by environment interactions (QEI) and QTL by trait interactions in
      the expression of complex traits like yield. This paper presents an overview of
      mixed model QTL methodology that is suitable for many types of populations and
      that allows predictive modeling of QEI, both for environmental and developmental
      gradients. Attention is also given to multi-trait QTL models which are essential
      to interpret the genetic basis of trait correlations. Biophysical (crop growth)
      model simulations are proposed as a complement to statistical QTL mapping for the
      interpretation of the nature of QEI and to investigate better methods for the
      dissection of complex traits into component traits and their genetic controls.

PMID- 20138000
TI  - Two-component signal transduction as potential drug targets in pathogenic
      bacteria.
AB  - Gene clusters contributing to processes such as cell growth and pathogenicity are
      often controlled by two-component signal transduction systems (TCSs). Specific
      inhibitors against TCS systems work differently from conventional antibiotics,
      and developing them into new drugs that are effective against various drug
      resistant bacteria may be possible. Furthermore, inhibitors of TCSs that control
      virulence factors may reduce virulence without killing the pathogenic bacteria.
      Previous TCS inhibitors targeting the kinase domain of the histidine kinase
      sensor suffered from poor selectivity. Recent TCS inhibitors, however, target the
      sensory domains of the sensors blocking the quorum sensing system, or target the
      essential response regulator. These new targets are introduced, together with
      several specific TCSs that have the potential to serve as effective drug targets.

PMID- 20138001
TI  - Summary of useful methods for two-component system research.
AB  - Since the discovery of protein phosphorylation in bacterial nitrogen assimilation
      and chemotaxis more than 30 years ago, many biochemical techniques for the
      analysis of two-component signal transduction systems have been developed. Over
      time the experimental conditions to follow the flow of phosphate groups from
      histidine kinases to the cognate response regulators in vitro have been fine
      tuned. Several approaches were applied to circumvent the instability of the
      phosphorylated form of response regulator proteins to analyze the structures of
      their activated forms. Recently, a FRET (fluorescence resonance energy transfer)
      assay was developed to monitor interactions of chemotaxis proteins in vivo. The
      availability of bacterial genome sequence databases has facilitated the
      identification of two-component systems and enabled prediction of interacting
      kinase-response regulators pairs.

PMID- 20138002
TI  - Two component systems in the spatial program of bacteria.
AB  - Despite being considered a relatively simple form of life, bacteria have revealed
      a high degree of structural organization, with the spatial destination of their
      components precisely regulated within the cell. Nevertheless, the primary signals
      that dictate differential distribution of cellular building blocks and
      physiological processes remain in most cases largely undisclosed. Signal
      transduction systems are no exception within this three-dimensional organization
      and two-component systems (TCS) involved in controlling cell division,
      differentiation, chemotaxis and virulence show specific and/or dynamic
      localization, engaging in the spatial program of the bacterial cell.

PMID- 20138003
TI  - Cavity ring-down observation of Yb(3+) optical absorption in room temperature
      solution.
AB  - Cavity ring-down spectroscopy is used to probe the optical absorption of the
      optical pseudo-two level system [Xe]4f(13) Yb(3+) in room temperature solution, a
      situation where the two-color pump-probe luminescence approach commonly used to
      study the other [Xe]4f(n) (2 < or = n < or = 12) trivalent lanthanide ions fails.
      A 1m optical cavity constructed from two highly reflective mirrors is used to
      obtain ring-down signals as a function of wavelength from 1 mL samples contained
      in a quartz cuvette placed in the center of the cavity. Absorption spectra
      constructed from these signals characteristic of the (6)H(15/2)-->(4)F(9/2)
      [Xe]4f(5) Dy(3+) and the (7)F(0)-->(5)D(0) [Xe]4f(6) Eu(3+) transitions are
      presented and compared to the corresponding single pass absorption and two-color
      pump-probe luminescence spectra to obtain sensitivity estimates. Finally the
      spectrum for the (2)F(5/2)-->(2)F(7/2) [Xe]4f(13) Yb(3+) transition for a model
      Yb(3+) complex in room temperature solution is obtained using cavity ring-down
      spectroscopy for the first time.

PMID- 20138004
TI  - Cutaneous silent period changes in Type 2 diabetes mellitus patients with small
      fiber neuropathy.
AB  - OBJECTIVE: Small myelinated (A-delta) and unmyelinated (C) somatic sensory fibers
      are initially affected and may be the earliest exhibited sign of neuropathy in
      glucose dysmetabolism. Cutaneous silent period (CSP) is an inhibitory spinal
      reflex and its afferents consist of A-delta nerve fibers. The aim of this study
      was to evaluate CSP changes in Type 2 diabetic patients with small fiber
      neuropathy. METHODS: Forty-three patients and 41 healthy volunteers were
      included. CSP latency and duration, as well as CSP latency difference of the
      upper and lower extremities, were examined. RESULTS: Nerve conduction studies
      were within normal limits in both groups. Lower extremity CSP latency was longer
      (122.1+/-15.5 vs. 96.4+/-6.4 ms; p<0.001), CSP duration was shorter (29.5+/-8.9
      vs. 43.1+/-5.0 ms; p<0.001), and latency difference was longer (48.1+/-12.6 vs.
      22.7+/-3.7; p<0.001) in patients than controls. The difference was more
      significant in patients with neuropathic pain. No significant difference existed
      in upper extremity on CSP evaluation. CONCLUSION: The CSP evaluation together
      with nerve conduction study, has been demonstrated to be beneficial and
      performance of latency difference in addition to CSP latency and duration may be
      a valuable parameter in electrophysiological assessment of diabetic patients with
      small fiber neuropathy. SIGNIFICANCE: An additional CSP evaluation may be
      considered in cases which nerve conduction studies do not provide sufficient
      information.

PMID- 20138005
TI  - Self-reported sleep disturbances during cannabis withdrawal in cannabis-dependent
      outpatients with and without opioid dependence.

PMID- 20138007
TI  - Angiotensin-converting enzyme gene polymorphism and risk of insulin resistance in
      PCOS.
AB  - The aim of this study was to establish the frequency of angiotensin-converting
      enzyme (ACE) insertion (I) or deletion (D) gene polymorphism in women with
      polycystic ovary syndrome (PCOS) and to examine the association of this
      polymorphism with insulin resistance. A total of 32 women with PCOS and 31
      healthy, age- and body mass index-matched controls were studied. Serum lipids,
      fasting glucose, insulin and other hormones concentrations were measured.
      Homeostasis model assessment was used to estimate insulin resistance (HOMA-IR).
      DNA was extracted from peripheral blood leukocytes and genotyping of ACE I/D
      polymorphism was carried out by polymerase chain reaction. ACE genotypes were
      distributed as follows: DD was present in 16 (50%), ID in 12 (37.5%) and II in
      four (12.5%) PCOS patients, and DD in seven (22.6%), ID in 20 (64.5%) and II in
      four (12.9%) of healthy subjects. The frequency of D and I alleles were found in
      69% and 31% of the PCOS group and 55% and 45% in the control group, respectively.
      There were no significant differences regarding the genotypic distribution and
      allelic frequency between the groups. However the ACE DD genotype was
      significantly associated with serum insulin concentrations and HOMA-IR
      measurement (both P=0.005). ACE DD genotype is associated with an increased
      insulin resistance in women with PCOS.

PMID- 20138006
TI  - Pathogenesis of human systemic lupus erythematosus: recent advances.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with manifestations
      derived from the involvement of multiple organs including the kidneys, joints,
      nervous system and hematopoietic organs. Immune system aberrations, as well as
      heritable, hormonal and environmental factors interplay in the expression of
      organ damage. Recent contributions from different fields have developed our
      understanding of SLE and reshaped current pathogenic models. Here, we review
      recent findings that deal with (i) genes associated with disease expression; (ii)
      immune cell molecular abnormalities that lead to autoimmune pathology; (iii) the
      role of hormones and sex chromosomes in the development of disease; and (iv)
      environmental and epigenetic factors thought to contribute to the expression of
      SLE. Finally, we highlight molecular defects intimately associated with the
      disease process of SLE that might represent ideal therapeutic targets and disease
      biomarkers.

PMID- 20138008
TI  - Human immunodeficiency and Hodgkin lymphoma.
AB  - Presentation of Hodgkin lymphoma (HL) is distinctive in the infected individual
      being more advanced, accompanied by B symptoms and the presence of extranodal
      disease particularly lymphadenopathy of the head and neck. Bone marrow
      involvement may be found in over 50% of cases. Virtually all co express gamma
      herpesvirus. Phenotypically there is prominence of the mixed-cellularity and
      lymphocyte depleted histopathologic subtypes that define an aggressive clinical
      course in comparison to other variants. Prior to the induction of cART, median
      survival was only 1-2 years. Notably the first chemotherapy trial using ABVD
      (doxorubicin, bleomycin, vinblastine, and dacarbazine) in 21 patients, without
      treating the viral infection, resulted in a 43% complete remission rate
      accompanied by severe haematological toxicities but did not extend median
      survival with this being 1.5 years matching the negative cases. Significant
      change accompanied concomitant anti-retroviral therapy that could be given safely
      even with dose intensive regimens exemplified by BEACOPP (bleomycin, etoposide,
      doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in 12
      patients or the Stanford V regimen (doxorubicin, vinblastine, mechlorethamine,
      etoposide, vincristine, bleomycin, prednisone) coupled with involved-field
      radiation for bulky disease studied in 59 patients. BEACOPP extended overall
      survival (OS) to 83% at 2 years. A similar trend was seen when using the Stanford
      V regimen with an OS rate of 51% at 3 years, disease-free survival (DFS) of 68%
      and freedom from progression (FFP) in 60%. Additional benefits accrued from
      supportive care with stimulatory peptides such as G-CSF and when combined with
      bacterial prophylaxis results approached that found in the uninfected reference
      group. Current consensus holds this particular lymphoma as still among the non
      AIDS defining cancers being lung, stomach, liver or anal despite these having
      recently gained more attention as several of these neoplasms may be occurring
      more commonly in the era of cART. While the relative risk of developing a non
      AIDS-defining neoplasm in HIV-infected persons on the average is 2-3 times, the
      risk for developing HL in HIV-infected cases impressively ranges between 5 and 25
      times when compared to the general population. Based on the precedent in which
      Kaposi sarcoma and the non-Hodgkin lymphomas distinctively alter the course of
      this retroviral infection in a way indistinguishable from concurrent Hodgkin
      lymphoma we propose that this entity be similarly regarded and the hypothesis
      tested in large randomised prospective study.

PMID- 20138009
TI  - Self-treatment of an ABO-incompatible blood transfusion.
AB  - Unfortunately, transfusion errors continue to pose a major clinical problem. In
      practice there is a remarkable lack of understanding of the reasons behind
      transfusion medicine, a worrying disregard for protocol and an offhand attitude
      to bedside checking. Clearly transfusion medicine education, as often said, must
      be more extensively incorporated into the core curriculum of medical, nursing and
      laboratory staff. In this immunological case report, following accurate pre
      transfusion procedures and routine laboratory testing, we highlight, once more,
      that it would be better for the patient to rely on proper bedside checking rather
      than on their own immune system in order to avoid serious side effects related to
      transfusions. Albeight this case we had "a happy ending", we must always bear in
      mind that one cannot compromise on safety and the quality care of patients.

PMID- 20138010
TI  - Adjunctive dexamethasone in meningitis: does value depend on clinical setting?

PMID- 20138011
TI  - Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual
      patient data.
AB  - BACKGROUND: Dexamethasone improves outcome for some patients with bacterial
      meningitis, but not others. We aimed to identify which patients are most likely
      to benefit from dexamethasone treatment. METHODS: We did a meta-analysis of
      individual patient data from the randomised, double-blind, placebo-controlled
      trials of dexamethasone for bacterial meningitis in patients of all ages for
      which raw data were available. The pre-determined outcome measures were death at
      the time of first follow-up, death or severe neurological sequelae at 1 month
      follow-up, death or any neurological sequelae at first follow-up, and death or
      severe bilateral hearing loss at first follow-up. Combined odds ratios (ORs) and
      tests for heterogeneity were calculated using conventional Mantel-Haenszel
      statistics. We also did exploratory analysis of hearing loss among survivors and
      other exploratory subgroup analyses by use of logistic regression. FINDINGS: Data
      from 2029 patients from five trials were included in the analysis (833 [41.0%]
      aged <15 years). HIV infection was confirmed or likely in 580 (28.6%) patients
      and bacterial meningitis was confirmed in 1639 (80.8%). Dexamethasone was not
      associated with a significant reduction in death (270 of 1019 [26.5%] on
      dexamethasone vs 275 of 1010 [27.2%] on placebo; OR 0.97, 95% CI 0.79-1.19),
      death or severe neurological sequelae or bilateral severe deafness (42.3%vs
      44.3%; 0.92, 0.76-1.11), death or any neurological sequelae or any hearing loss
      (54.2%vs 57.4%; 0.89, 0.74-1.07), or death or severe bilateral hearing loss
      (36.4%vs 38.9%; 0.89, 0.73-1.69). However, dexamethasone seemed to reduce hearing
      loss among survivors (24.1%vs 29.5%; 0.77, 0.60-0.99, p=0.04). Dexamethasone had
      no effect in any of the prespecified subgroups, including specific causative
      organisms, pre-dexamethasone antibiotic treatment, HIV status, or age. Pooling of
      the mortality data with those of all other published trials did not significantly
      change the results. INTERPRETATION: Adjunctive dexamethasone in the treatment of
      acute bacterial meningitis does not seem to significantly reduce death or
      neurological disability. There were no significant treatment effects in any of
      the prespecified subgroups. The benefit of adjunctive dexamethasone for all or
      any subgroup of patients with bacterial meningitis thus remains unproven.
      FUNDING: Wellcome Trust UK.

PMID- 20138012
TI  - Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate
      Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner.
AB  - Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating
      angiogenesis, cancer cell proliferation, and invasion. We demonstrate that CAFs
      also mediate tumor-enhancing inflammation. Using a mouse model of squamous skin
      carcinogenesis, we found a proinflammatory gene signature in CAFs isolated from
      dysplastic skin. This signature was maintained in CAFs from subsequent skin
      carcinomas and was evident in mammary and pancreatic tumors in mice and in
      cognate human cancers. The inflammatory signature was already activated in CAFs
      isolated from the initial hyperplastic stage in multistep skin tumorigenesis.
      CAFs from this pathway promoted macrophage recruitment, neovascularization, and
      tumor growth, activities that are abolished when NF-kappaB signaling was
      inhibited. Additionally, we show that normal dermal fibroblasts can be "educated"
      by carcinoma cells to express proinflammatory genes.

PMID- 20138013
TI  - FcRgamma activation regulates inflammation-associated squamous carcinogenesis.
AB  - Chronically activated leukocytes recruited to premalignant tissues functionally
      contribute to cancer development; however, mechanisms underlying pro- versus anti
      tumor programming of neoplastic tissues by immune cells remain obscure. Using the
      K14-HPV16 mouse model of squamous carcinogenesis, we report that B cells and
      humoral immunity foster cancer development by activating Fcgamma receptors
      (FcgammaRs) on resident and recruited myeloid cells. Stromal accumulation of
      autoantibodies in premalignant skin, through their interaction with activating
      FcgammaRs, regulate recruitment, composition, and bioeffector functions of
      leukocytes in neoplastic tissue, which in turn promote neoplastic progression and
      subsequent carcinoma development. These findings support a model in which B
      cells, humoral immunity, and activating FcgammaRs are required for establishing
      chronic inflammatory programs that promote de novo carcinogenesis.

PMID- 20138014
TI  - RecQ-dependent death-by-recombination in cells lacking RecG and UvrD.
AB  - Maintenance of genomic stability is critical for all cells. Homologous
      recombination (HR) pathways promote genome stability using evolutionarily
      conserved proteins such as RecA, SSB, and RecQ, the Escherichia coli homologue of
      five human proteins at least three of which suppress genome instability and
      cancer. A previous report indicated that RecQ promotes the net accumulation in
      cells of intermolecular HR intermediates (IRIs), a net effect opposite that of
      the yeast and two human RecQ homologues. Here we extend those conclusions. We
      demonstrate that cells that lack both UvrD, an inhibitor of RecA-mediated strand
      exchange, and RecG, a DNA helicase implicated in IRI resolution, are inviable. We
      show that the uvrD recG cells die a "death-by-recombination" in which IRIs
      accumulate blocking chromosome segregation. First, their death requires RecA HR
      protein. Second, the death is accompanied by cytogenetically visible failure to
      segregate chromosomes. Third, FISH analyses show that the unsegregated
      chromosomes have completed replication, supporting the hypothesis that unresolved
      IRIs prevented the segregation. Fourth, we show that RecQ and induction of the
      SOS response are required for the accumulation of replicated, unsegregated
      chromosomes and death, as are RecF, RecO, and RecJ. ExoI exonuclease and MutL
      mismatch-repair protein are partially required. This set of genes is similar but
      not identical to those that promote death-by-recombination of DeltauvrD Deltaruv
      cells. The data support models in which RecQ promotes the net accumulation in
      cells of IRIs and RecG promotes resolution of IRIs that form via pathways not
      wholly identical to those that produce the IRIs resolved by RuvABC. This implies
      that RecG resolves intermediates other than or in addition to standard Holliday
      junctions resolved by RuvABC. The role of RecQ in net accumulation of IRIs may be
      shared by one or more of its human homologues.

PMID- 20138015
TI  - Quantification of topotecan by liquid chromatography-mass spectrometry (LC-MS).
      Application to intestinal transport using rat everted gut sacs.
AB  - Topetecan is an important anti-cancer drug that has recently become available as
      an oral formulation. In order to study its intestinal absorption in vitro and a
      potential drug-drug interaction with the anti-emetic ondansetron, a sensitive and
      accurate method for the analysis of topotecan in biological media was required.
      We developed a liquid-liquid extraction method at pH 7.0-7.5 with a recovery of
      85% and which took into account the complex chemical behaviour of topotecan
      related to the lactone opening and the keto-enol tautomerism. This enabled us to
      validate a new specific and sensitive LC-MS method of analysis, with satisfactory
      inter- and intra-day repeatability and accuracy. The method was applied to a
      study of topotecan uptake in rat everted gut sacs that showed that, despite being
      a P-glycoprotein substrate like topotecan, ondansetron did not interfere with
      topotecan uptake.

PMID- 20138016
TI  - Brainstorm: occupational choice, bipolar illness and creativity.
AB  - Although economists have analyzed earnings, unemployment, and labor force
      participation for those with bipolar illness, occupational choice has yet to be
      explored. Psychological and medical studies often suggest an association between
      bipolar illness and creative achievement, but they tend to focus on eminent
      figures, case studies, or small samples. We seek to examine occupational
      creativity of non-eminent individuals with bipolar disorder. We use Epidemiologic
      Catchment Area data to estimate a multinomial logit model matched to an index of
      occupational creativity. Those with bipolar illness appear to be
      disproportionately concentrated in the most creative occupational category.
      Nonparametric kernel density estimates reveal that the densities of the
      occupational creativity variable for the bipolar and non-bipolar individuals
      significantly differ in the ECA data, and suggest that the probability of
      engaging in creative activities on the job is higher for bipolar than non-bipolar
      workers.

PMID- 20138017
TI  - [Chromosome 9P deletion: Gonadal dysgenesis associated with mental retardation
      and hypoplasia of the corpus callosum: A contiguous gene syndrome?].
AB  - BACKGROUND: Many genes are involved in testicular differentiation. The
      alterations of these genes are responsible for sexual differentiation disorders
      with 46 XY karyotype. CASE: We report the case of a newborn who had an
      interscrotal hypospadias, palpable gonads and hypoplastic penis. Karyotype 46 XY.
      Abdominal ultrasound revealed testes and absence of Mullerian remnants. There was
      a good response to the short gonadotrophin test. At one year he had signs of
      psychomotor retardation and hypotonia. The magnetic resonance revealed frontal
      temporal atrophy and a decrease in the corpus callosum. Testicular biopsy was
      compatible with gonadal dysgenesis. A preoperative cystography showed a vaginal
      remnant. Due to the presence of a sexual differentiation disorder, psychomotor
      retardation and facial dysmorphism, we requested a high-resolution karyotype:
      deletion 46, XY, del (9p) (p23-pter). Ish tel (9p-). DISCUSSION: Many genes are
      involved in testicular differentiation, some of which also affect the development
      of other tissues. In the short arm of chromosome 9, two genes, DMRT1 and DMRT2,
      are involved in sexual differentiation. Their alterations have also been
      described as causing mental retardation. In the evaluation of 46,XY disorders of
      sex differentiation, the accompanying signs are very important for guiding the
      genetic study.

PMID- 20138018
TI  - Response letter re: Objective assessment of surgical performance and its impact
      on a national selection programme. J Plast Reconstr Aesthet Surg 2009;62:1543-9.

PMID- 20138019
TI  - beta2- and beta3-, but not beta1-adrenergic receptors are involved in
      osteogenesis of mouse mesenchymal stem cells via cAMP/PKA signaling.
AB  - The osteogenic capacity of mesenchymal stem cells (MSCs) and the importance of
      beta-adrenergic signals in bone formation and resorption have been well
      investigated. However, little is known about the development of beta-adrenergic
      receptor (beta-AR) systems and the role of beta-adrenergic signals in osteogenic
      differentiation of MSCs, which is critically important in bone physiology and
      pharmacology. In this study, we demonstrated that both the mRNA and protein
      levels of beta2- and beta3-AR are up-regulated following osteogenesis of mouse
      MSCs. We also established that beta-AR agonists negatively while antagonists
      positively affect MSC osteogenesis. Both beta2- and beta3-AR are involved in MSC
      osteogenesis, with beta2-AR being dominant. The effect of beta-ARs on MSC
      osteogenesis is partly mediated via the cAMP/PKA signaling. These findings
      suggest that MSC is also a target for beta-adrenergic regulation and beta
      adrenergic signaling plays a role in MSC osteogenesis.

PMID- 20138020
TI  - Actin assembly controlled by GDP-Rab27a is essential for endocytosis of the
      insulin secretory membrane.
AB  - We have recently reported that GDP-bound Rab27a regulates endocytosis of the
      insulin secretory membrane via its binding to coronin 3, an actin-binding
      protein. The aim of this study was to examine the participation of actin assembly
      in the Rab27a-dependent regulation of endocytosis using a pancreatic beta cell
      line, MIN6. Coronin 3 promoted F-actin bundling only in the presence of GDP
      Rab27a. This effect was independent of coronin-3-binding to the actin-related
      proteins 2 and 3 (Arp2/3). Uptake of anti-phogrin-lumen antibody into MIN6 was
      inhibited by anti-coronin-3-C antibody which recognizes the actin-binding site.
      This inhibition was also observed with coronin-3-R28D, which lacks in actin
      binding. These results suggest that coronin 3 is a genuine GDP-Rab27a effector,
      and that controls endocytosis of the secretory membrane via modulating actin
      assembly in pancreatic beta-cells.

PMID- 20138021
TI  - Mitochondria generated nitric oxide protects against permeability transition via
      formation of membrane protein S-nitrosothiols.
AB  - Mitochondria generated nitric oxide (NO) regulates several cell functions
      including energy metabolism, cell cycling, and cell death. Here we report that
      the NO synthase inhibitors (L-NAME, L-NNA and L-NMMA) administered either in
      vitro or in vivo induce Ca2+-dependent mitochondrial permeability transition
      (MPT) in rat liver mitochondria via a mechanism independent on changes in the
      energy state of the organelle. MPT was determined by the occurrence of
      cyclosporin A sensitive mitochondrial membrane potential disruption followed by
      mitochondrial swelling and Ca2+ release. In in vitro experiments, the effect of
      NOS inhibitors was dose-dependent (1 to 50 microM). In addition to cyclosporin A,
      L-NAME-induced MPT was sensitive to Mg2+ plus ATP, EGTA, and to a lower degree,
      to catalase and dithiothreitol. In contrast to L-NAME, its isomer D-NAME did not
      induce MPT. L-NAME-induced MPT was associated with a significant decrease in both
      the rate of NO generation and the content of mitochondrial S-nitrosothiol. Acute
      and chronic in vivo treatment with L-NAME also promoted MPT and decreased the
      content of mitochondrial S-nitrosothiol. SNAP (a NO donor) prevented L-NAME
      mediated MPT and reversed the decrease in the rate of NO generation and in the
      content of S-nitrosothiol. We propose that S-nitrosylation of critical membrane
      protein thiols by NO protects against MPT.

PMID- 20138022
TI  - Effects of protons on macroscopic and single-channel currents mediated by the
      human P2X7 receptor.
AB  - Human P2X7 receptors (hP2X7Rs) belong to the P2X family, which opens an intrinsic
      cation channel when challenged by extracellular ATP. hP2X7Rs are expressed in
      cells of the inflammatory and immune system. During inflammation, ATP and protons
      are secreted into the interstitial fluid. Therefore, we investigated the effect
      of protons on the activation of hP2X7Rs. hP2X7Rs were expressed in Xenopus laevis
      oocytes and activated by the agonists ATP or benzoyl-benzoyl-ATP (BzATP) at
      different pH values. The protons reduced the hP2X7R-dependent cation current
      amplitude and slowed the current deactivation depending on the type and
      concentration of the agonist used. These effects can be explained by (i) the
      protonation of ATP, which reduces the effective concentration of the agonist
      ATP(4-) at the high- and low-affinity ATP activation site of the hP2XR, and (ii)
      direct allosteric inhibition of the hP2X7R channel opening that follows ATP(4-)
      binding to the low-affinity activation site. Due to the hampered activation via
      the low-affinity activation site, a low pH (as observed in inflamed tissues)
      leads to a relative increase in the contribution of the high-affinity activation
      site for hP2X7R channel opening.

PMID- 20138023
TI  - Cell-penetrating peptide exploited syndecans.
AB  - Cell-penetrating peptides (CPPs) are short peptides capable of translocating
      across the plasma membrane of live cells and transporting conjugated compounds
      intracellularly. Fifteen years after discovering the first model cationic CPPs,
      penetratin and TAT, CPP internalization is still challenging many questions.
      Particularly it has been unknown whether CPPs enter the cells with or without
      mediation of a specific surface receptor. Here we report that syndecan-4, the
      universally expressed isoform of the syndecan family of transmembrane
      proteoglycans, binds and mediates transport of the three most frequently utilized
      cationic CPPs (penetratin, octaarginine and TAT) into the cells. Quantitative
      uptake studies and mutational analyses demonstrate that attachment of the
      cationic CPPs is mediated by specific interactions between the heparan sulfate
      chains of syndecan-4 and the CPPs. Protein kinase C alpha is also heavily
      involved in the uptake mechanism. The collected data give the first direct
      evidence on the receptor-mediated uptake of cationic CPPs and may replace the
      long-thought, but already contradicted membrane penetration hypothesis. Thus our
      study might give an answer for a decade long debate and foster the development of
      rationalized, syndecan-4 targeted novel delivery technologies.

PMID- 20138024
TI  - The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated
      insulin secretion by direct activation of the alpha2-adrenergic receptors in beta
      cells.
AB  - Treatment with the dopamine receptor D2 (DRD2) agonist bromocriptine improves
      metabolic features in obese patients with type 2 diabetes by a still unknown
      mechanism. In the present study, we investigated the acute effect of
      bromocriptine and its underlying mechanism(s) on insulin secretion both in vivo
      and in vitro. For this purpose, C57Bl6/J mice were subjected to an
      intraperitoneal glucose tolerance test (ipGTT) and a hyperglycemic (HG) clamp
      60min after a single injection of bromocriptine or placebo. The effects of
      bromocriptine on glucose-stimulated insulin secretion (GSIS), cell membrane
      potential and intracellular cAMP levels were also determined in INS-1E beta
      cells. We report here that bromocriptine increased glucose levels during ipGTT in
      vivo, an effect associated with a dose-dependent decrease in GSIS. During the HG
      clamp, bromocriptine reduced both first-phase and second-phase insulin response.
      This inhibitory effect was also observed in INS-1E beta cells, in which
      therapeutic concentrations of bromocriptine (0.5-50nM) decreased GSIS.
      Mechanistically, neither cellular energy state nor cell membrane depolarization
      was affected by bromocriptine whereas intracellular cAMP levels were
      significantly reduced, suggesting involvement of G-protein-coupled receptors.
      Surprisingly, the DRD2 antagonist domperidone did not counteract the effect of
      bromocriptine on GSIS, whereas yohimbine, an antagonist of the alpha2-adrenergic
      receptors, completely abolished bromocriptine-induced inhibition of GSIS. In
      conclusion, acute administration of bromocriptine inhibits GSIS by a DRD2
      independent mechanism involving direct activation of the pancreatic alpha2
      adrenergic receptors. We suggest that treatment with bromocriptine promotes beta
      cells rest, thereby preventing long-lasting hypersecretion of insulin and
      subsequent beta cell failure.

PMID- 20138025
TI  - Bisdemethylcurcumin and structurally related hispolon analogues of curcumin
      exhibit enhanced prooxidant, anti-proliferative and anti-inflammatory activities
      in vitro.
AB  - Curcumin, a component of turmeric (Curcuma longa), exhibits anti-inflammatory and
      anti-proliferative activities through the generation of reactive oxygen species
      (ROS). Curcumin (diferuloylmethane) contains two hydroxyl, two methoxy and two
      phenyl groups but how these groups contribute to its activity is poorly
      understood. We synthesized analogues that varied in inclusion of these groups and
      compared their activity. We found that bisdemethylcurcumin (BDC) was more potent
      than curcumin as an anti-inflammatory agent as indicated by suppression of TNF
      induced NF-kappaB activation, more potent as an anti-proliferative agent, and
      more potent in inducing ROS. Hispolon, which lacks one aromatic unit in relation
      to curcumin, also exhibited enhanced anti-inflammatory and anti-proliferative
      activities. When synthetic curcumin (Cur-S) was compared with bisdemethylcurcumin
      (BDC), hispolon, hispolon methyl ether (HME), dehydroxy hispolon (DH), hydroxy
      hispolon (HH), methoxy hispolon methyl ether (MHME), and methoxy hispolon (MH),
      we found that following order of anti-inflammatory activity:
      BDC=Hispolon>HME>HH>Cur-S>MHME>MH>DH; for anti-proliferative:
      Hispolon>BDC>MHME>Cur-S>MH>HME=HH>DH; and for prooxidant: BDC>Cur
      S=MHME>HH>MH+HME>DH (254-1414 mean fluorescence intensity). Thus, dehydroxy
      hispolon was least potent for all three activities. Overall the results indicate
      that the substitution of a hydroxyl group for a methoxy group at the meta
      positions of the phenyl rings in curcumin significantly enhanced the anti
      inflammatory activity, and the removal of phenyl ring at the 7(th) position of
      the heptadiene back bone and addition of hydroxyl group significantly increased
      the anti-proliferative activity of curcumin.

PMID- 20138026
TI  - A simple yeast-based system for analyzing inhibitor resistance in the human
      cancer drug targets Hsp90alpha/beta.
AB  - Heat shock protein 90 (Hsp90), a highly conserved molecular chaperone, is one of
      the most promising targets for cancer drug development. Whether any resistance to
      these Hsp90 inhibitor drugs could arise by Hsp90 mutation is still unknown. Yeast
      is readily engineered so that its essential Hsp90 function is provided by either
      isoform of the human cytosolic Hsp90, Hsp90alpha or Hsp90beta. However, its high
      intrinsic resistance to most drugs poses a major obstacle to the use of such
      Hsp90alpha- or Hsp90beta-expressing yeast cells as a model system to analyse
      whether drug resistance might arise by Hsp90 mutation. In order to overcome this
      problem, we have generated a strain that is both hypersensitive to Hsp90
      inhibitors as it lacks multiple drug resistance genes, and in which different
      heterologous and mutant Hsp90s can be expressed by plasmid exchange. It is not
      rendered appreciably stress sensitive when made to express Hsp90alpha or
      Hsp90beta as its sole form of Hsp90. Should there be any development of
      resistance to the Hsp90 drugs now in cancer clinic trials, this system can
      provide a rapid initial test of whether any single nucleotide polymorphism
      appearing within the coding regions of Hsp90alpha or Hsp90beta could be a
      contributory factor in this resistance. We have used this strain to demonstrate
      that significant levels of resistance to the Hsp90 inhibitors radicicol and 17
      allylamino-demethoxygeldanamycin (17-AAG) are generated as a result of the same
      single point mutation within the native Hsp90 of yeast (A107N), the human
      Hsp90alpha (A121N) and the human Hsp90beta (A116N).

PMID- 20138027
TI  - Bax deficiency mediated drug resistance can be reversed by endoplasmic reticulum
      stress induced death signaling.
AB  - Tumors often acquire drug resistance due to functional loss of pro apoptotic gene
      Bax, a critical and essential component of cell death rendering them insensitive
      to most anti-tumor agents. Compounds that can induce Bax independent apoptotic
      cell death are expected to overcome such drug resistance. We have employed a live
      cell based screening platform to identify potential compounds that can induce
      programmed cell death in Bax deficiency. Release of cytochrome C from
      mitochondria into the cytosol is a decisive initial event required for the
      caspase dependent cell death. We have engineered both wild type and Bax knock out
      colon cancer cells stably expressing cytochrome C with EGFP fusion protein to
      identify compounds that can trigger cytochrome C release in both cells with equal
      efficiency. In the fluorescent translocation assay, most of the drugs tested
      failed to induce cytochrome C release in Bax deficient cells validating the
      sensitivity of the assay. This study identified five lead compounds such as
      thapsigargin, tunicamycine, MG132, kaempferol and camptothecin that could induce
      cytochrome C release in both wild type and Bax deficient cells with equal
      potency. All the positive hits induced ER stress signaling as evidenced by up
      regulation of Grp78. Studies with a Bak deficient cells indicate that Bak
      deficiency confers protection to cells from ER stress through autophagy. Further
      studies revealed that ER stress inducing agents are capable of triggering
      classical mitochondrial apoptotic cell death through the conformational
      activation of Bak, substantiating the potential of this pathway in designing
      drugs against Bax deficiency mediated drug resistance.

PMID- 20138028
TI  - Hedgehog-dependent down-regulation of the tumor suppressor, vitamin D3 up
      regulated protein 1 (VDUP1), precedes lamina development in Drosophila.
AB  - The tumor suppressor vitamin D(3) up-regulated protein 1 (VDUP1) is expressed
      throughout the developing and mature Drosophila nervous system, but its
      regulatory pathways are not well understood. Within the developing Drosophila
      visual system, down-regulation of VDUP1 in lamina precursor cells (LPCs)
      coincided with the arrival of retinal axons into the lamina target field,
      suggesting VDUP1 regulation by an axonally transmitted signal. Hedgehog (Hh) is a
      signal well known to coordinate LPC proliferation and differentiation in response
      to retinal axon innervation, and analysis of orthologous dvdup1 promoters
      identified an evolutionarily conserved binding site for the Hh-dependent
      transcription factor cubitus interruptus (Ci). Hh-dependent regulation of VDUP1
      in the developing lamina was confirmed in Hh loss-of-function backgrounds where
      VDUP1 expression was maintained in LPCs, inhibiting both cell proliferation and
      lamina neurogenesis. This putative coupling of VDUP1 to the Hh signaling pathway
      may provide novel insights into the mechanisms controlling brain growth and
      development.

PMID- 20138029
TI  - Cytotoxic activity of naphthoquinones with special emphasis on juglone and its 5
      O-methyl derivative.
AB  - The cytotoxicity of nine naphthoquinones (NQ) was assayed against HL-60
      (leukaemia), MDA-MB-435 (melanoma), SF-295 (brain) and HCT-8 (colon), all human
      cancer cell lines, and peripheral blood mononuclear cells (PBMC), as
      representatives of normal cells, after 72h of incubation. 5-Methoxy-1,4
      naphthoquinone was the most active compound, showing IC(50) values in the range
      of 0.31 (1.7microM) in HL-60 to 0.88microg/mL (4.7microM) in SF-295 and IC(50) of
      0.69microg/mL (3.7microM) against PBMC. With the introduction of a bromo
      substituent in position 2 or 3 of juglone, the IC(50) significantly decreased,
      regardless of the position on the NQ moiety. However, compared with juglone
      methyl ether, the halogen substitution decreased the activity. To further
      understand the mechanism underlying the cytotoxicity of 5-methoxy-1,4
      naphthoquinone, studies involving DNA fragmentation, cell cycle analysis,
      phosphatidyl serine externalization, mitochondrial depolarization and activation
      of caspases 8 and 3/7 were performed in HL-60 cell line, using doxorubicin as a
      positive control. The results indicate that the cytotoxic 5-methoxy-1,4
      naphthoquinone activates caspases 8 and 3/7 and thus induces apoptosis
      independent of mitochondria.

PMID- 20138031
TI  - RP-HPLC/MS-APCI analysis of odd-chain TAGs from Rhodococcus erythropolis
      including some regioisomers.
AB  - We used reversed phase liquid chromatography-atmospheric pressure chemical
      ionization mass spectrometry (RP-HPLC/MS-APCI) for direct analysis of
      triacylglycerols (TAGs) from four different cultivations of Rhodococcus
      erythropolis CCM 2595. This technique enabled us to identify and quantify the
      specific molecular species of TAGs directly from lipid extracts of the bacterium,
      including the determination of their basic characteristics such as retention time
      and mass spectra. A total of 17 TAGs having at least one odd-numbered-chain FA
      (fatty acid) were found. This is the first time when odd-chain TAGs,
      predominantly with pentadecanoic, margaric, and margaroleic acids, were
      identified. Multiple linear regression analyses were used for predicting
      retention times of molecular species, predominantly of odd-chain TAGs.
      Cultivations on two different substrates at two different temperatures (20 and 30
      degrees C) showed that only temperature had any effect on the content of TAGs. In
      cultivations with succinate as a carbon source the content of these TAGs
      increased by half (i.e., from 23.5 to 34.2%) when the cultivation temperature was
      lowered from 30 to 20 degrees C. The content of the PoPoMo, PoMoO and PPoMo (see
      Table 1) TAGs containing the odd-numbered-chain margaroleic acid rose from 0.0 to
      7.1% while in cultivation on phenol as a carbon source the lowering of
      cultivation temperature caused an increase of these TAGs from 0.5 to 6.7%.

PMID- 20138030
TI  - Acetylcholinesterase: from 3D structure to function.
AB  - By rapid hydrolysis of the neurotransmitter, acetylcholine, acetylcholinesterase
      terminates neurotransmission at cholinergic synapses. Acetylcholinesterase is a
      very fast enzyme, functioning at a rate approaching that of a diffusion
      controlled reaction. The powerful toxicity of organophosphate poisons is
      attributed primarily to their potent inhibition of acetylcholinesterase.
      Acetylcholinesterase inhibitors are utilized in the treatment of various
      neurological disorders, and are the principal drugs approved thus far by the FDA
      for management of Alzheimer's disease. Many organophosphates and carbamates serve
      as potent insecticides, by selectively inhibiting insect acetylcholinesterase.
      The determination of the crystal structure of Torpedo californica
      acetylcholinesterase permitted visualization, for the first time, at atomic
      resolution, of a binding pocket for acetylcholine. It also allowed identification
      of the active site of acetylcholinesterase, which, unexpectedly, is located at
      the bottom of a deep gorge lined largely by aromatic residues. The crystal
      structure of recombinant human acetylcholinesterase in its apo-state is similar
      in its overall features to that of the Torpedo enzyme; however, the unique
      crystal packing reveals a novel peptide sequence which blocks access to the
      active-site gorge.

PMID- 20138032
TI  - Evaluation of APTIMA Combo 2 for cross-reactivity with oropharyngeal Neisseria
      species and other microorganisms.

PMID- 20138033
TI  - Plasma osteopontin concentration correlates with the severity of hepatic fibrosis
      and inflammation in HCV-infected subjects.
AB  - BACKGROUND: The association between OPN level and the histological severity of
      hepatic fibrosis and inflammation in hepatitis C virus (HCV) induced liver
      fibrosis remains unknown. METHODS: 120 chronic HCV-infected subjects and 75
      controls were enrolled in this study. Assessment of liver histology was performed
      based on liver biopsy. Plasma OPN levels were determined. RESULTS: Significant
      differences were noted in the mean plasma OPN levels between subjects with
      extensive fibrosis and those with mild fibrosis (4.29+/-1.01 ng/ml vs. 2.15+/
      0.63 ng/ml, respectively; p<0.001). Similarly, the subjects with higher
      histological activity index (HAI) score had elevated OPN levels than those with
      mild HAI score (4.41+/-1.11 ng/ml vs. 2.25+/-0.94 ng/ml, respectively; p<0.001).
      The correlation between the plasma OPN levels and the severity of liver fibrosis
      degree and HAI score were noted (r=0.945, and r=0.788, respectively both
      p<0.001). Logistic regression analysis showed that serum OPN was an independent
      risk factor contributing to extensive liver fibrosis and inflammation (p=0.0018
      and p<0.001, respectively) in patients with HCV subjects. CONCLUSION: The plasma
      OPN level is correlated with the severity of liver fibrosis and inflammation,
      suggesting OPN could be used as a biomarker to evaluate the severity of liver
      damages in HCV subjects.

PMID- 20138034
TI  - Self-complementary AAV5 vector facilitates quicker transgene expression in
      photoreceptor and retinal pigment epithelial cells of normal mouse.
AB  - To clarify whether transduction efficiency and cell type specificity of self
      complementary (sc) AAV5 vectors are similar to those of standard, single-stranded
      AAV5 vectors in normal retina, one micro liter of scAAV5-smCBA-GFP vector (1 x
      10(12) genome-containing particles/ml) and AAV5-smCBA-GFP vector (1 x 10(12)
      genome-containing particles/ml) were subretinally or intravitreally (in both
      cases through the cornea) injected into the right and left eyes of adult C57BL/6J
      mice, respectively. On post-injection day (PID) 1, 2, 5, 7, 10, 14, 21, 28 and
      35, eyes were enucleated; retinal pigment epithelium (RPE) wholemounts,
      neuroretinal wholemounts and eyecup sections were prepared to evaluate green
      fluorescent protein (GFP) expression by fluorescent microscopy. GFP expression
      following trans-cornea subretinal injection of scAAV5-smCBA-GFP vector was first
      detected in RPE wholemounts around PID 1 and in neuroretinal wholemounts between
      PID 2 and 5; GFP expression peaked and stabilized between PID 10-14 in RPE
      wholemounts and between P14 and P21 in neuroretinal wholemounts with strong,
      homogeneous green fluorescence covering the entire wholemounts. The frozen
      sections supported the following findings from the wholemounts: GFP expression
      appeared first in RPE around PID 1-2 and soon spread to photoreceptors (PR)
      cells; by PID 7, moderate GFP expression was found mainly in PR and RPE layers;
      between PID 14 and 21, strong and homogenous GFP expression was observed in RPE
      and PR cells. GFP expression following subretinal injection of AAV5-smCBA-GFP was
      first detected in RPE wholemounts around PID 5-7 and in neuroretinal wholemounts
      around PID 7-10; ssAAV5-mediated GFP expression peaked at PID 21 in RPE
      wholemounts and around PID 28 in neuroretinal wholemounts; sections from AAV5
      treated eyes also supported findings obtained from wholemounts: GFP expression
      was first detected in RPE and then spread to the PR cells. Peak GFP expression in
      RPE mediated by scAAV5 was similar to that mediated by AAV5. However, peak GFP
      expression mediated by scAAV5 in PR cells was stronger than that mediated by
      AAV5. No GFP fluorescence was detected in any retinal cells (RPE wholemounts,
      neuroretinal wholemounts and retinal sections) after trans-cornea intravitreal
      delivery of either scAAV5-GFP or AAV5-GFP. Neither scAAV5 nor AAV5 can transduce
      retinal cells following trans-cornea intravitreal injection. The scAAV5 vector
      used in this study directs an earlier onset of transgene expression than the
      matched AAV5 vector, and has stronger transgene expression in PR cells following
      subretinal injection. Our data confirm the previous reports that scAAV vectors
      have an earlier onset than the standard, single strand AAV vectors (Natkunarajah
      et al., 2008; Yokoi et al., 2007). scAAV5 vectors may be more useful than
      standard, single-stranded AAV vector when addressing certain RPE and/or PR cell
      related models of retinal dystrophy, particularly for mouse models of human
      retinitis pigmentosa that require rapid and robust transgene expression to
      prevent early degeneration in PR cells.

PMID- 20138036
TI  - A novel role of microtubular cytoskeleton in the dynamics of caspase-dependent
      Fas/CD95 death receptor complexes during apoptosis.
AB  - The activation of cysteine-aspartic proteases or caspases and the dynamic
      arrangement of cytoskeletal components are crucial during apoptosis. Here we
      describe the fate of Fas downstream of the FasL-induced internalization step,
      including formation of caspase-dependent SDS-stable Fas complexes, which is
      mediated by cytoskeleton integrity. We show, in particular, that following FasL
      treatment, the Fas lower aggregate complex can be co-immunoprecipitated with
      tubulin and an active form of caspase-8 and that this interaction contributes to
      the propagation of FasL-induced cell death. The importance of cytoskeletal
      components during FasL-induced apoptosis is highlighted by our detection of a
      pool of microtubule-associated Fas complexes.

PMID- 20138035
TI  - Inhibition of aldose reductase attenuates endotoxin signals in human non
      pigmented ciliary epithelial cells.
AB  - Chronic inflammatory diseases such as autoimmune and bacterial infections are
      associated with an elevated risk of ocular inflammation. Ciliary epithelial cells
      that play an important role in maintaining aqueous humor dynamics and homeostasis
      of anterior segment of eye are continuously exposed to inflammatory markers
      during infections and injury. Lipopolysacchharide (LPS), a Gram-negative
      bacterial endotoxin, dysregulates aqueous humor (AqH) homeostasis by inducing
      inflammatory changes. We have investigated how inhibition of a polyol pathway
      enzyme, aldose reductase (AR), alters LPS-induced inflammatory changes in human
      non-pigmented ciliary epithelial cells (hNPECs). The stimulation of hNPECs with
      LPS (1 microg/ml) caused increased secretion of inflammatory markers such as
      PGE(2) and NO in the culture medium as well as increased expression of COX-2 and
      iNOS proteins in cell extracts. LPS also increased phosphorylation of MAPKs
      (ERK1/2) and SAPK/JNK and activation of redox-sensitive transcription factors NF
      kappaB and AP-1 in hNPECs and inhibition of AR by zopolrestat and sorbinil
      ameliorated these changes. Further, LPS-induced decrease in the expression of
      Na/K-ATPase in hNPECs was restored by AR inhibitors. Similar results were
      observed in ciliary bodies of LPS-injected rats. Taken together, our results
      suggest that AR plays an important role in the LPS-induced inflammatory changes
      in hNPECs and that inhibition of AR could be a novel therapeutic approach for
      ocular inflammation.

PMID- 20138037
TI  - Adjunctive functional pharyngeal electrical stimulation reverses swallowing
      disability after brain lesions.
AB  - BACKGROUND & AIMS: Oropharyngeal dysphagia is an important disability that occurs
      after stroke; it contributes to aspiration pneumonia and death, and current
      modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore
      examined the role of pharyngeal electrical stimulation (PES) in expediting human
      swallowing recovery after experimental (virtual) and actual (stroke) brain
      lesions. METHODS: First, healthy subjects (n = 13) were given 1-Hz repetitive
      transcranial magnetic stimulation to induce a unilateral virtual lesion in
      pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked
      potentials and swallow accuracy were recorded before and after the lesion to
      assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent
      either a dose-response study, to determine optimal parameters for PES (n = 22),
      or were assigned randomly to groups given either active or sham (control) PES (n
      = 28). The primary end point was the reduction of airway aspiration at 2 weeks
      postintervention. RESULTS: In contrast to sham PES, active PES reversed the
      cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and
      was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02).
      After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0)
      produced improved airway protection compared with controls (P = .038). Active PES
      also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0;
      P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log
      rank test, P = 0.038). CONCLUSIONS: This pilot study of PES confirms that it is a
      safe neurostimulation intervention that reverses swallowing disability after
      virtual lesion or stroke.

PMID- 20138039
TI  - A novel gastrokine, Gkn3, marks gastric atrophy and shows evidence of adaptive
      gene loss in humans.
AB  - BACKGROUND & AIMS: Gastrokines are stomach mucus cell-secreted proteins; 2
      gastrokines are known, GKN1 and GKN2. Gastrokine expression is lost in gastric
      cancer, indicating a possible function in tumor suppression. We have identified a
      third gastrokine gene in mammals. METHODS: Gkn3 was characterized by studies of
      molecular structure, evolutionary conservation, and tissue expression as well as
      transcriptional/translational outcome in mouse genetic models of gastric
      pathology. The functional consequences of Gkn3 overexpression were evaluated in
      transfected cell lines. RESULTS: Gkn3 encodes a secreted (approximately 19
      kilodalton) protein that is co-expressed with trefoil factor (Tff)2 in the distal
      stomach and discriminates a Griffinia simplicifolia lectin (GS)-II-positive mucus
      neck cell (MNC) subpopulation in the proximal stomach. In humans, widespread
      homozygosity for a premature stop codon polymorphism, W59X, has likely rendered
      GKN3 non-functional. Population genetic analysis revealed an ancestral GKN3 read
      through allele that predominates in Africans and indicates the rapid expansion of
      W59X among non-Africans during recent evolution. Mouse Gkn3 expression is
      strongly up-regulated in (Tff2-deficient) gastric atrophy, a pre-cancerous state
      that is typically associated with Helicobacter pylori and marks a non
      proliferative, GS-II positive lineage with features of spasmolytic polypeptide
      expressing metaplasia (SPEM). Gkn3 overexpression inhibits proliferation in
      gastric epithelial cell lines, independently of incubation with recombinant human
      TFF2 or apoptosis. CONCLUSIONS: Gkn3 encodes a novel, functionally distinct
      gastrokine that is overexpressed and might restrain epithelial cell proliferation
      in gastric atrophy. Spread of the human GKN3 stop allele W59X might have been
      selected for among non-Africans because of its effects on pre-neoplastic outcomes
      in the stomach.

PMID- 20138038
TI  - Aberrant epithelial-mesenchymal Hedgehog signaling characterizes Barrett's
      metaplasia.
AB  - BACKGROUND & AIMS: The molecular mechanism underlying epithelial metaplasia in
      Barrett's esophagus remains unknown. Recognizing that Hedgehog signaling is
      required for early esophageal development, we sought to determine if the Hedgehog
      pathway is reactivated in Barrett's esophagus, and if genes downstream of the
      pathway could promote columnar differentiation of esophageal epithelium. METHODS:
      Immunohistochemistry, immunofluorescence, and quantitative real-time polymerase
      chain reaction were used to analyze clinical specimens, human esophageal cell
      lines, and mouse esophagi. Human esophageal squamous epithelial (HET-1A) and
      adenocarcinoma (OE33) cells were subjected to acid treatment and used in
      transfection experiments. Swiss Webster mice were used in a surgical model of
      bile reflux injury. An in vivo transplant culture system was created using
      esophageal epithelium from Sonic hedgehog transgenic mice. RESULTS: Marked up
      regulation of Hedgehog ligand expression, which can be induced by acid or bile
      exposure, occurs frequently in Barrett's epithelium and is associated with
      stromal expression of the Hedgehog target genes PTCH1 and BMP4. BMP4 signaling
      induces expression of SOX9, an intestinal crypt transcription factor, which is
      highly expressed in Barrett's epithelium. We further show that expression of
      Deleted in Malignant Brain Tumors 1, the human homologue of the columnar cell
      factor Hensin, occurs in Barrett's epithelium and is induced by SOX9. Finally,
      transgenic expression of Sonic hedgehog in mouse esophageal epithelium induces
      expression of stromal Bmp4, epithelial Sox9, and columnar cytokeratins.
      CONCLUSIONS: Epithelial Hedgehog ligand expression may contribute to the
      initiation of Barrett's esophagus through induction of stromal BMP4, which
      triggers reprogramming of esophageal epithelium in favor of a columnar phenotype.

PMID- 20138041
TI  - Glucose-dependent insulinotropic polypeptide is expressed in pancreatic islet
      alpha-cells and promotes insulin secretion.
AB  - BACKGROUND & AIMS: Glucose-dependent insulinotropic polypeptide (GIP) and the
      proglucagon product glucagon-like peptide-1 (GLP-1) are gastrointestinal hormones
      that are released in response to nutrient intake and promote insulin secretion.
      Interestingly, a subset of enteroendocrine cells express both GIP and GLP-1. We
      sought to determine whether GIP also might be co-expressed with proglucagon in
      pancreatic alpha-cells. METHODS: We assessed GIP expression via reverse
      transcription polymerase chain reaction, in situ hybridization, and
      immunohistochemistry. We developed a novel bioassay to measure GIP release from
      isolated islets, compared the biological activities of full-length and truncated
      GIP, and assessed the impact of immunoneutralization of islet GIP on glucose
      stimulated insulin secretion in isolated islets. RESULTS: GIP messenger RNA was
      present in mouse islets; GIP protein localized to islet alpha-cells of mouse,
      human, and snake pancreas, based on immunohistochemical analyses. However, using
      a C-terminal GIP antibody, immunoreactivity was detected in islets from
      prohormone convertase (PC) 2 knockout but not wild-type mice. Bioactive GIP was
      secreted from mouse and human islets after arginine stimulation. In the perfused
      mouse pancreas, GIP(1-42) and amidated GIP(1-30) had equipotent insulinotropic
      actions. Finally, immunoneutralization of GIP secreted by isolated islets
      decreased glucose-stimulated insulin secretion. CONCLUSIONS: GIP is expressed in
      and secreted from pancreatic islets; in alpha-cells, PC2 processes proGIP to
      yield a truncated but bioactive form of GIP that differs from the PC1/3-derived
      form from K-cells. Islet-derived GIP promotes islet glucose competence and also
      could support islet development and/or survival.

PMID- 20138042
TI  - Alpha cell-specific Men1 ablation triggers the transdifferentiation of glucagon
      expressing cells and insulinoma development.
AB  - BACKGROUND & AIMS: The tumor suppressor menin is recognized as a key regulator of
      pancreatic islet development, proliferation, and beta-cell function, whereas its
      role in alpha cells remains poorly understood. The purpose of the current study
      was to address this issue in relation to islet tumor histogenesis. METHODS: We
      generated alpha cell-specific Men1 mutant mice with Cre/loxP technology and
      carried out analyses of pancreatic lesions developed in the mutant mice during
      aging. RESULTS: We showed that, despite the alpha-cell specificity of the GluCre
      transgene, both glucagonomas and a large amount of insulinomas developed in
      mutant mice older than 6 months, accompanied by mixed islet tumors.
      Interestingly, the cells sharing characteristics of both alpha and beta cells
      were identified shortly after the appearance of menin-deficient alpha cells but
      well before the tumor onset. Using a genetic cell lineage tracing analysis, we
      demonstrated that insulinoma cells were directly derived from
      transdifferentiating glucagon-expressing cells. Furthermore, our data indicated
      that the expression of Pdx1, MafA, Pax4, and Ngn3 did not seem to be required for
      the initiation of this transdifferentiation. CONCLUSIONS: Our work shows cell
      transdifferentiation as a novel mechanism involved in islet tumor development and
      provides evidence showing that menin regulates the plasticity of differentiated
      pancreatic alpha cells in vivo, shedding new light on the mechanisms of islet
      tumorigenesis.

PMID- 20138043
TI  - Does capsule endoscopy improve outcomes in obscure gastrointestinal bleeding?
      Randomized trial versus dedicated small bowel radiography.
AB  - BACKGROUND & AIMS: Capsule endoscopy improves the diagnostic yield in patients
      with obscure gastrointestinal (GI) bleeding, but whether it improves outcomes is
      uncertain. METHODS: Patients with obscure GI bleeding and negative upper
      endoscopy, colonoscopy, and push enteroscopy were randomly assigned to capsule
      endoscopy or dedicated small bowel contrast radiography. Patients returned at 1,
      2, 3, 6, 9, and 12 months for follow-up visits and to check hemoglobin level. The
      primary endpoint was further bleeding. RESULTS: The predefined sample size of 136
      patients (54 overt bleeding, 82 occult bleeding) was enrolled. Diagnostic yield
      was 20 (30%) with capsule vs 5 (7%) with radiography (difference = 23%; 95% CI:
      11%-36%). Further bleeding with capsule versus radiography occurred in 20 (30%)
      versus 17 (24%) (difference, 6%; 95% confidence interval [CI], -9% to 21%),
      subsequent diagnostic or therapeutic interventions for bleeding were performed in
      17 (26%) versus 15 (21%) (difference, 4%; 95% CI, -10% to 19%), subsequent
      hospitalizations for bleeding were required in 8 (12%) versus 4 (6%) (difference,
      6%; 95% CI, -3% to 16%), and subsequent blood transfusions were given in 5 (8%)
      versus 4 (6%) (difference, 2%; 95% CI, -7% to 10%). Further bleeding was more
      common in patients presenting with overt bleeding than in those with occult
      bleeding (21/54 [39%] vs 16/82 [20%]; difference, 19%; 95% CI, 4% to 35%).
      CONCLUSIONS: The significant improvement in diagnostic yield with capsule
      endoscopy may not translate into improved outcomes in a population with obscure
      GI bleeding. Most patients do well whether or not abnormalities are identified,
      and additional diagnostic or therapeutic interventions may be required whether or
      not capsule endoscopy identifies a source of bleeding.

PMID- 20138044
TI  - Mucin gene deficiency in mice impairs host resistance to an enteric parasitic
      infection.
AB  - BACKGROUND & AIMS: Hyperplasia of mucin-secreting intestinal goblet cells
      accompanies a number of enteric infections, including infections by nematode
      parasites. Nevertheless, the precise role of mucins in host defense in nematode
      infection is not known. We investigated the role of the mucin (Muc2) in worm
      expulsion and host immunity in a model of nematode infection. METHODS: Resistant
      (BALB/c, C57BL/6), susceptible (AKR), and Muc2-deficient mouse strains were
      infected with the nematode, Trichuris muris, and worm expulsion, energy status of
      the whipworms, changes in mucus/mucins, and inflammatory and immune responses
      were investigated after infection. RESULTS: The increase in Muc2 production,
      observed exclusively in resistant mice, correlated with worm expulsion. Moreover,
      expulsion of the worms from the intestine was significantly delayed in the Muc2
      deficient mice. Although a marked impairment in the development of periodic acid
      Schiff (PAS)-stained intestinal goblet cells was observed in Muc2-deficient mice,
      as infection progressed a significant increase in the number of PAS-positive
      goblet cells was observed in these mice. Surprisingly, an increase in Muc5ac, a
      mucin normally expressed in the airways and stomach, was observed after infection
      of only the resistant animals. Overall, the mucus barrier in the resistant mice
      was less permeable than that of susceptible mice. Furthermore, the worms isolated
      from the resistant mice had a lower energy status. CONCLUSIONS: Mucins are an
      important component of innate defense in enteric infection; this is the first
      demonstration of the important functional contribution of mucins to host
      protection from nematode infection.

PMID- 20138045
TI  - Twenty years of ISAREN: an amphibian biologist in Wonderland.
AB  - The 6th International Symposium on Amphibian and Reptilian Endocrinology and
      Neurobiology (ISAREN), the former International Symposium on Amphibian
      Endocrinology (ISAE), was recently held in Berlin. ISAREN developed from two
      symposia on amphibian biology held in European countries in 1988-1990. In this
      article, the history of ISAREN was briefly stated. In addition, some of the
      topics of our researches carried out in collaboration with several groups, using
      various amphibian species during the past 20 years and/or presented in the past
      symposia were reviewed. The topics included the discovery of pancreatic
      chitinase, involvement of growth hormone in vitellogenin synthesis, changes of
      ANF-like immunoreactivity in the frogs sent into the space, discovery of a
      peptide sex-pheromone, origin of the epithelial pituitary, and hypothalamic
      regulation of thyroid-stimulating hormone.

PMID- 20138046
TI  - Elimination of Taenia solium transmission to pigs in a field trial of the TSOL18
      vaccine in Cameroon.
AB  - A pilot field trial of the TSOL18 vaccine was undertaken in Cameroon. Two hundred
      and forty, 2-3 month-old piglets were distributed to 114 individual households in
      pairs. Vaccinated animals received three immunisations with 200 microg TSOL18
      plus 5 mg Quil A and 30 mg/kg oxfendazole at the time of the second immunisation.
      Necropsies were undertaken when the pigs were approximately 12 months of age.
      Viable Taenia solium cysticerci were identified in 20 control pigs (prevalence
      19.6%); no cysticerci were found in any of the vaccinated animals (P<0.0001).
      Combined application of TSOL18 vaccination and a single oxfendazole treatment in
      pigs may be a relatively simple and sustainable procedure that has the potential
      to control T. solium transmission in endemic areas and, indirectly, reduce the
      number of new cases of neurocysticercosis in humans.

PMID- 20138047
TI  - Efficient mRNA electroporation of peripheral blood mononuclear cells to detect
      memory T cell responses for immunomonitoring purposes.
AB  - To date, the number of immunotherapy vaccines in clinical trials increases
      exponentially. To evaluate the efficacy of these clinical vaccination trials, we
      fervently need cellular immunomonitoring tools. In this study, we present a newly
      developed short-time assay which allows direct ex vivo analysis of multi-epitope
      antigen-specific T cell immune responses. This novel method is based on mRNA
      electroporation of isolated peripheral blood mononuclear cells (PBMC). Fresh and
      cryopreserved PBMC of both healthy volunteers as well as of allogeneic stem cell
      transplanted patients enrolled in a cytomegalovirus (CMV) dendritic cell
      vaccination trial were electroporated with CMV pp65-encoding mRNA. Using a direct
      IFN-gamma EliSPOT and intracellular cytokine flow cytometry we detected
      significantly higher numbers of CMV pp65-specific IFN-gamma-secreting T cells as
      compared to the assay with non-treated PBMC and as compared to PBMC
      electroporated with mRNA coding for an irrelevant protein. Compared to
      conventional methods to evaluate T cell-mediated immune responses, this method is
      time-saving and less labor-intensive because it obviates the need for in vitro
      cultured antigen-presenting cells and because an overnight incubation is
      sufficient for activation of T cells. Moreover, the use of CMV pp65-encoding mRNA
      will broaden the immune response because it covers every epitope with potential
      relevance. This is a major advantage compared to the recognition of a single
      epitope covered by a HLA-restricted peptides. In summary, we developed a highly
      efficient mRNA electroporation protocol for fresh and cryopreserved PBMC. This
      novel method is a rapid and elegant tool and will be convenient for monitoring
      the cellular immune status of patients in a clinical vaccination setting.

PMID- 20138048
TI  - Active immunization induces toxicity of diphtheria toxin in diphtheria resistant
      mice--implications for neuroinflammatory models.
AB  - Cell-type specific expression of the human diphtheria toxin receptor in generally
      toxin resistant mice represents an innovative approach for the selective
      depletion of pre-defined cell populations. We demonstrate that in wildtype mice
      diphtheria toxin--in concentrations otherwise well tolerated--is highly toxic and
      lethal together with active immunization irrespective of the immunogenic peptide
      applied. We found increased lung cellularity as only pathological abnormality.
      Animal models of inflammatory diseases requiring active immunization including
      experimental autoimmune encephalomyelitis may thus not be applicable in
      diphtheria receptor transgenic mice pointing to a major limitation of this
      otherwise technically interesting approach.

PMID- 20138049
TI  - A receptor-independent, cell-based JAK activation assay for screening for JAK3
      specific inhibitors.
AB  - New immunosuppressive compounds with less systemic toxicity that could replace
      calcineurin inhibitors are urgently needed. For identification of specific
      inhibitors of JAK3, a potential new drug target, from large chemical libraries we
      developed a cell-based screening system. TEL-JAK fusion proteins composed of an
      oligomerization domain of TEL and kinase and/or pseudokinase domains of JAKs
      provided constitutive activation of JAKs without receiving a signal from the
      cytokine receptors. These fusion proteins also induced STAT5b phosphorylation in
      the absence of cytokine receptors. Both the kinase and pseudokinase domains of
      JAKs were required for full activation of the JAKs, and four copies of STAT5
      response elements provided the greatest luciferase activity. The sensitivity and
      specificity of the system was evaluated using specific JAK3, JAK2, or MEK
      inhibitors. Thus, we generated a receptor-independent, cell-based selective
      screening system for specific JAK3 inhibitors, which is easily convertible to a
      high-throughput screening platform.

PMID- 20138050
TI  - Cost of oviposition site selection in a water strider Aquarius paludum insularis:
      egg mortality increases with oviposition depth.
AB  - Females generally avoid selecting sites for oviposition which have a high
      predation risk to increase offspring survival. Previous studies have focused on
      costs to ovipositing females. However, although offspring may also incur costs by
      being oviposited at low predation risk sites, no studies have focused on costs to
      offspring. Such costs to offspring were examined by using Aquarius paludum
      insularis, females of which avoid eggs parasitism by ovipositing at deep sites.
      Deep sites are safe from egg parasitism but may be unsuitable for hatching due to
      environmental factors. We examined the costs to offspring at deep sites by
      comparing the hatching rate, the duration to hatching and the proportion of
      drowned larvae between eggs that were set at three levels of water depth (0 cm,
      25 cm and 50 cm depth). While the hatching rate at 50 cm was lower than that at 0
      cm, the rate at 25 cm did not differ from that at 0 cm. Duration to hatching and
      the proportion of drowned larvae did not differ between the three depths. It is
      suggested that the declining survival rate of A. paludum eggs was due to
      increased water pressure at greater depth. Such a cost may exist in other species
      and such an observation may aid in understanding oviposition site selection.

PMID- 20138051
TI  - The effects of age and social interactions on innate immunity in a leaf-cutting
      ant.
AB  - Both developmental and environmental factors shape investment in costly immune
      defences. Social insect workers have different selection pressures on their
      innate immune system compared to non-social insects because workers do not
      reproduce and their longevity affects the fitness of relatives. Furthermore,
      hygienic behavioural defences found in social insects can result in increased
      survival after fungal infection, although it is not known if there is modulation
      in physiological immune defence associated with group living vs. solitary living.
      Here we investigated whether physiological immune defence is affected by both age
      and the short-term presence or absence of nestmates in the leaf-cutting ant
      Acromyrmex octospinosus. We predicted that older ants would show immune
      senescence and that group living may result in prophylactic differences in immune
      defence compared to solitarily kept ants. We kept old and young workers alone or
      in nestmate groups for 48h and assayed a key innate immune system enzyme,
      expressing phenoloxidase (PO) and its stored precursor (proPO), a defence that
      acts immediately, i.e. it is constitutive. Short-term solitary living did not
      affect PO or proPO levels relative to group living controls and we found no
      evidence for immunosenescence in proPO. However, we found a significant increase
      in active PO in older workers, which is consistent with two non-mutually
      exclusive explanations: it could be an adaptive response or indicative of
      immunosenescence. Our results suggest that future studies of immunosenescence
      should consider both active immune effectors in the body, such as PO, and the
      stored potential to express immune defences, such as proPO.

PMID- 20138052
TI  - Introduction to the special issue on insect respiration.

PMID- 20138053
TI  - Novel cross-stage solitarising effect of gregarious-phase adult desert locust
      (Schistocerca gregaria (Forskal)) pheromone on hoppers.
AB  - Previous studies had demonstrated stage differentiation in the cohesion
      (aggregation) pheromone systems of the desert locust, Schistocerca gregaria. In
      laboratory arena, the nymphal and adult stages responded aggregatively to their
      own pheromone, but dispersed evenly within the arena in the presence of the
      other. In the present study, we explored the effects of longer-term contact of
      field gregarious hopper bands and laboratory crowd-reared nymphs with the major
      constituent of the adult pheromone. During the first few days, hoppers in treated
      bands became relatively hyperactive. Over the next few days, their movements
      became random and they stopped marching as coherent groups, they started to roost
      for longer periods on vegetations, and they fragmented into smaller and smaller
      groupings and individuals. When attacked by birds, they demonstrated subdued
      levels of collective defensive behaviour compared to normal hoppers, and there
      were clear signs of increased predation and cannibalism at the roosting sites. In
      cage experiments, crowd-reared nymphs treated with the pheromone component became
      hyperactive, showed abnormal diel patterns and reduced feeding on plants but
      increased cannibalism. Our observations show that the major adult pheromone
      constituent has a solitarising effect on gregarious hoppers. The mechanism
      underlying this effect and the potential of the agent in desert locust control
      are discussed.

PMID- 20138054
TI  - Midgut and fatbody mitochondrial transhydrogenase activities during larval-pupal
      development of the tobacco hornworm, Manduca sexta.
AB  - Midgut and fatbody mitochondria from fifth larval instar Manduca sexta display a
      membrane-associated transhydrogenase that catalyzes a reversible hydride ion
      transfer between NADP(H) and NAD(H). The NADPH-forming activity occurs as a
      nonenergy- or energy-linked activity with energy for the latter derived from
      either electron transport-dependent NADH or succinate utilization, or ATP
      hydrolysis by Mg(++)-dependent ATPase. During the ten-day developmental period
      preceding the larval-pupal molt (fifth larval instar), significant peaks in the
      mitochondrial transhydrogenase activities of midgut and fatbody tissues were
      noted and these peaks were coincident with the onset of wandering behavior and
      with the fifty-fold increase in ecdysone 20-monooxygenase (E20-M) activity
      previously reported for M. sexta midgut. Since E20-M preferentially uses NADPH in
      catalyzing ecdysone conversion to the physiologically active molting hormone, 20
      hydroxyecdysone, the physiological and developmental significance of the
      mitochondrial, NADPH-forming energy-linked transhydrogenations were made
      apparent. Moreover, that the increases in all transhydrogenase activities
      resulted from de novo enzyme synthesis were indicated by the cycloheximide
      dependent reductions in these activities.

PMID- 20138055
TI  - Electrical stimulation of sympathetic neurons induces autocrine/paracrine effects
      of NGF mediated by TrkA.
AB  - Neuronal remodeling with increased sympathetic innervation density has been
      implicated in the pathogenesis of atrial fibrillation (AF). Recently, increased
      transcardiac nerve growth factor (NGF) levels were observed in a canine model of
      AF. Whether atrial myocytes or cardiac sympathetic neurons are the source of
      neurotrophins, and whether NGF is the main neurotrophic factor contributing to
      sympathetic nerve sprouting (SNS) in AF still remains unclear. Therefore,
      neonatal rat atrial myocytes were cultured under conditions of high frequency
      electrical field stimulation (HFES) to mimic rapid atrial depolarization.
      Likewise, sympathetic neurons from the superior cervical ganglia of neonatal rats
      were exposed to HFES to simulate the physiological effect of sympathetic
      stimulation. Real-time PCR, ELISA and Western blots were performed to analyze the
      expression pattern of NGF and neurotrophin-3 (NT-3). Baseline NGF and NT-3
      content was 3-fold higher in sympathetic neurons than in atrial myocytes
      (relative NGF protein expression: 1+/-0.0 vs. 0.37+/-0.11, all n=5, p<0.05). HFES
      of sympathetic neurons induced a frequency dependent NGF and NT-3 gene and
      protein up-regulation (relative NGF protein expression: 0Hz=1+/-0.0 vs.
      5Hz=1.13+/-0.19 vs. 50Hz=1.77+/-0.08, all n=5, 0Hz/5Hz vs. 50Hz p<0.05), with a
      subsequent increase of growth associated protein 43 (GAP-43) expression and
      morphological SNS. Moreover, HFES of sympathetic neurons increased the tyrosine
      kinase A (TrkA) receptor expression. HFES induced neurotrophic effects could be
      abolished by lidocaine, TrkA blockade or NGF neutralizing antibodies, while NT-3
      neutralizing antibodies had no significant effect on SNS. In neonatal rat atrial
      myocytes, HFES resulted in myocyte hypertrophy accompanied by an increase in NT-3
      and a decrease in NGF expression. In summary, this study provides evidence that
      high-rate electrical stimulation of sympathetic neurons mediates nerve sprouting
      by an increase in NGF expression that targets the TrkA receptor in an
      autocrine/paracrine manner.

PMID- 20138056
TI  - Structural basis for catalysis by the mono- and dimetalated forms of the dapE
      encoded N-succinyl-L,L-diaminopimelic acid desuccinylase.
AB  - Biosynthesis of lysine and meso-diaminopimelic acid in bacteria provides
      essential components for protein synthesis and construction of the bacterial
      peptidoglycan cell wall. The dapE operon enzymes synthesize both meso
      diaminopimelic acid and lysine and, therefore, represent potential targets for
      novel antibacterials. The dapE-encoded N-succinyl-L,L-diaminopimelic acid
      desuccinylase functions in a late step of the pathway and converts N-succinyl-L,L
      diaminopimelic acid to L,L-diaminopimelic acid and succinate. Deletion of the
      dapE gene is lethal to Helicobacter pylori and Mycobacterium smegmatis,
      indicating that DapE's are essential for cell growth and proliferation. Since
      there are no similar pathways in humans, inhibitors that target DapE may have
      selective toxicity against only bacteria. A major limitation in developing
      antimicrobial agents that target DapE has been the lack of structural
      information. Herein, we report the high-resolution X-ray crystal structures of
      the DapE from Haemophilus influenzae with one and two zinc ions bound in the
      active site, respectively. These two forms show different activity. Based on
      these newly determined structures, we propose a revised catalytic mechanism of
      peptide bond cleavage by DapE enzymes. These structures provide important insight
      into catalytic mechanism of DapE enzymes as well as a structural foundation that
      is critical for the rational design of DapE inhibitors.

PMID- 20138057
TI  - Antigenic characteristics of rhinovirus chimeras designed in silico for enhanced
      presentation of HIV-1 gp41 epitopes [corrected].
AB  - The development of an effective AIDS vaccine remains the most promising long-term
      strategy to combat human immunodeficiency virus (HIV)/AIDS. Here, we report
      favorable antigenic characteristics of vaccine candidates isolated from a
      combinatorial library of human rhinoviruses displaying the ELDKWA epitope of the
      gp41 glycoprotein of HIV-1. The design principles of this library emerged from
      the application of molecular modeling calculations in conjunction with our
      knowledge of previously obtained ELDKWA-displaying chimeras, including knowledge
      of a chimera with one of the best 2F5-binding characteristics obtained to date.
      The molecular modeling calculations identified the energetic and structural
      factors affecting the ability of the epitope to assume conformations capable of
      fitting into the complementarity determining region of the ELDKWA-binding,
      broadly neutralizing human mAb 2F5. Individual viruses were isolated from the
      library following competitive immunoselection and were tested using ELISA and
      fluorescence quenching experiments. Dissociation constants obtained using both
      techniques revealed that some of the newly isolated chimeras bind 2F5 with
      greater affinity than previously identified chimeric rhinoviruses. Molecular
      dynamics simulations of two of these same chimeras confirmed that their HIV
      inserts were partially preorganized for binding, which is largely responsible for
      their corresponding gains in binding affinity. The study illustrates the utility
      of combining structure-based experiments with computational modeling approaches
      for improving the odds of selecting vaccine component designs with preferred
      antigenic characteristics. The results obtained also confirm the flexibility of
      HRV as a presentation vehicle for HIV epitopes and the potential of this platform
      for the development of vaccine components against AIDS.

PMID- 20138058
TI  - Two intramolecular isopeptide bonds are identified in the crystal structure of
      the Streptococcus gordonii SspB C-terminal domain.
AB  - Streptococcus gordonii is a primary colonizer and is involved in the formation of
      dental plaque. This bacterium expresses several surface proteins. One of them is
      the adhesin SspB, which is a member of the Antigen I/II family of proteins. SspB
      is a large multi-domain protein that has interactions with surface molecules on
      other bacteria and on host cells, and is thus a key factor in the formation of
      biofilms. Here, we report the crystal structure of a truncated form of the SspB C
      terminal domain, solved by single-wavelength anomalous dispersion to 1.5 A
      resolution. The structure represents the first of a C-terminal domain from a
      streptococcal Antigen I/II protein and is comprised of two structurally related
      beta-sandwich domains, C2 and C3, both with a Ca(2+) bound in equivalent
      positions. In each of the domains, a covalent isopeptide bond is observed between
      a lysine and an asparagine, a feature that is believed to be a common
      stabilization mechanism in Gram-positive surface proteins. S. gordonii biofilms
      contain attachment sites for the periodontal pathogen Porphyromonas gingivalis
      and the SspB C-terminal domain has been shown to have one such recognition motif,
      the SspB adherence region. The motif protrudes from the protein, and serves as a
      handle for attachment. The structure suggests several additional putative binding
      surfaces, and other binding clefts may be created when the full-length protein is
      folded.

PMID- 20138059
TI  - Generation and characterization of a chimeric rabbit/human Fab for co
      crystallization of HIV-1 Rev.
AB  - Rev is a key regulatory protein of human immunodeficiency virus type 1. Its
      function is to bind to viral transcripts and effect export from the nucleus of
      unspliced mRNA, thereby allowing the synthesis of structural proteins. Despite
      its evident importance, the structure of Rev has remained unknown, primarily
      because Rev's proclivity for polymerization and aggregation is an impediment to
      crystallization. Monoclonal antibody antigen-binding domains (Fabs) have proven
      useful for the co-crystallization of other refractory proteins. In the present
      study, a chimeric rabbit/human anti-Rev Fab was selected by phage display,
      expressed in a bacterial secretion system, and purified from the media. The Fab
      readily solubilized polymeric Rev. The resulting Fab/Rev complex was purified by
      metal ion affinity chromatography and characterized by analytical
      ultracentrifugation, which demonstrated monodispersity and indicated a 1:1 molar
      stoichiometry. The Fab binds with very high affinity, as determined by surface
      plasmon resonance, to a conformational epitope in the N-terminal half of Rev. The
      complex forms crystals suitable for structure determination. The ability to serve
      as a crystallization aid is a new application of broad utility for chimeric
      rabbit/human Fab. The corresponding single-chain antibody (scFv) was also
      prepared, offering the potential of intracellular antibody therapeutics against
      human immunodeficiency virus type 1.

PMID- 20138060
TI  - Using adaptive model predictive control to customize maintenance therapy
      chemotherapeutic dosing for childhood acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly
      one-quarter of patients experience a disease relapse. However, it has been shown
      that individualizing therapy for childhood ALL patients by adjusting doses based
      on the blood concentration of active drug metabolite could significantly improve
      treatment outcome. An adaptive model predictive control (MPC) strategy is
      presented in which maintenance therapy for childhood ALL is personalized using
      routine patient measurements of red blood cell mean corpuscular volume as a
      surrogate for the active drug metabolite concentration. A clinically relevant
      mathematical model is developed and used to describe the patient response to the
      chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient
      specific. During the course of treatment, the patient-specific parameters are
      adaptively identified using recurrent complete blood count measurements, which
      sufficiently constrain the patient parameter uncertainty to support customized
      adjustments of the drug dose. While this work represents only a first step toward
      a quantitative tool for clinical use, the simulated treatment results indicate
      that the proposed mathematical model and adaptive MPC approach could serve as
      valuable resources to the oncologist toward creating a personalized treatment
      strategy that is both safe and effective.

PMID- 20138061
TI  - Low-copy repeats on chromosome 22q11.2 show replication timing switches, DNA
      flexibility peaks and stress inducible asynchrony, sharing instability features
      with fragile sites.
AB  - The 22q11.2 region is a hotspot for chromosomal rearrangements mediated by LCR22A
      D low-copy repeats. Sequence motifs and homology-driven mechanisms have been
      suggested to mediate rearrangements. Nevertheless, recent evidence has emphasized
      the role of functional properties in genome instability, suggesting that
      replication timing transition regions could be peculiarly prone to genetic
      damage. In this work, we show that an early-late replication-transition zone is
      localised within LCR22A, the shared proximal endpoint of the majority of
      deletions and duplications of 22q11.2 region. Transition zone is characterized by
      asynchronous replication and by a DNA flexibility peak, features which are
      relevant for double-strand breaks and rearrangements at fragile sites. This and
      other flexibility peaks, associated with less relevant replication anomalies, are
      present in clusters inside LCR22A, B and D. All of them are composed of modules
      of AT-rich sequences, DNA satellites, and a HIV-1 integration site; moreover,
      they have coincidental position with boundaries of duplicons inside segmental
      duplications and with breakpoints of recurrent translocations. Noteworthy,
      flexibility peaks also lay at breakpoints of translocation partner chromosomes,
      three of which, 1p21.2, 8q24.13 and 11q23.3, have been positioned inside known
      common fragile sites. In many cases peaks are associated with potential matrix
      attachment regions (MARs). We propose that, similarly to fragile sites,
      replication perturbation and flexibility peaks may mediate strand breakage and
      rearrangements. Consistently with this view we show that the replication timing
      transition zone detected inside LCR22A is susceptible to replicative stress by
      aphidicolin, known inducer of fragile sites. These findings emphasize the
      significance of mutagenic exposure for the constitutional syndrome origin.

PMID- 20138062
TI  - Repeated anabolic androgenic steroid treatment causes antidepressant-reversible
      alterations of the hypothalamic-pituitary-adrenal axis, BDNF levels and behavior.
AB  - Abuse of anabolic androgenic steroids (AASs) is frequently associated with
      changes in mood, including depression. However, the nature of this association is
      still largely unexplored. As a model of AAS abuse, we used male adult rats
      injected for 4 weeks with either nandrolone or stanozolol at daily doses (5
      mg/kg, s.c.) that are considered equivalent to those abused by humans on a
      milligram per kilogram of body weight basis. AAS treatment reduced levels of
      brain-derived neurotrophic factor in the hippocampus and prefrontal cortex,
      reduced the expression of low-affinity glucocorticoid receptors in the
      hippocampus, and increased morning trough basal plasma corticosterone levels. All
      these changes have been related to the pathophysiology of major depressive
      disorder. Accordingly, rats treated with nandrolone or stanozolol showed an
      increased immobility time in the forced swim test, which is widely used for the
      screening of antidepressant drugs. All effects produced by AASs were prevented by
      co-administration with the classical antidepressant, chlorimipramine. The
      evidence that supraphysiological doses of AASs induce changes indicative of a
      depressive state in normal rats, raises the concern that AAS abuse in humans may
      cause depression regardless of exposure to stress or other risk factors.

PMID- 20138063
TI  - Decreased numbers of progenitor cells but no response to antidepressant drugs in
      the hippocampus of elderly depressed patients.
AB  - Imaging studies have consistently documented hippocampal volume reductions in
      depression. Although depressive disorders are traditionally considered to have a
      neurochemical basis, recent studies suggest that impairments of structural
      plasticity contribute to the volume reductions and the related cognitive changes.
      This might result from repeated periods of stress that are a wellknown risk
      factor for depression. Adult neurogenesis is a prominent example of
      neuroplasticity that in rodents, is reduced by stress but stimulated by
      antidepressant drugs. Although reductions in neurogenesis have been proposed to
      contribute to the etiology of depression, only two studies have so far examined
      hippocampal cytogenesis in depression, but this was in a limited number of
      subjects with considerable interindividual variation, and these studies came to
      different conclusions. We therefore collected hippocampal tissue of 10 elderly
      control subject and 10 well-matched depressed patients that were highly
      comparable in terms of age, sex, pH-CSF and postmortem delay, and tested whether
      the numbers of MCM2-positive progenitors and PH3-positive proliferating cells
      were altered by depression or antidepressant treatment. A significant reduction
      was found in MCM2-, but not PH3-immunopositive cells in depression. Although this
      result is consistent with the concept that structural plasticity is decreased in
      depression, we could not confirm that antidepressant drugs had a stimulatory
      effect on these cells. This discrepancy may relate to anatomical differences, in
      medication, to neurogenesis-independent mechanisms of antidepressant action, or
      the age of the patients that was higher than in previous studies. Whether the
      reduction is a cause or consequence of depression awaits to be determined.

PMID- 20138064
TI  - Language representation and processing in fluent bilinguals: electrophysiological
      evidence for asymmetric mapping in bilingual memory.
AB  - The purpose of this investigation was to test the assumption of asymmetric
      mapping between words and concepts in bilingual memory as proposed by the Revised
      Hierarchical Model (RHM, Kroll & Stewart, 1994). Twenty four Spanish-English
      bilinguals (experiment 1) and twenty English-Spanish bilinguals (experiment 2)
      were presented with pairs of words, one in English and one in Spanish, and asked
      to indicate whether or not the words had the same meaning. In half the trials the
      Spanish word preceded the English, and in the other half the English word
      preceded the Spanish. In each condition half of the words had the same meaning,
      and the experiment included both concrete and abstract word trials. Event-related
      potentials (ERPs) were used to examine lexical-semantic activation during word
      translation. As predicted, a direction-dependent translation asymmetry was
      observed in the magnitude of the N400 repetition effect. Specifically, the N400
      effect was larger during backward translation (L2-L1) than during forward
      translation (L1-L2) in both groups of bilinguals. Results are considered in the
      context of different models of bilingual memory.

PMID- 20138065
TI  - Syntax, concepts, and logic in the temporal dynamics of language comprehension:
      evidence from event-related potentials.
AB  - Logic has been intertwined with the study of language and meaning since
      antiquity, and such connections persist in present day research in linguistic
      theory (formal semantics) and cognitive psychology (e.g., studies of human
      reasoning). However, few studies in cognitive neuroscience have addressed logical
      dimensions of sentence-level language processing, and none have directly compared
      these aspects of processing with syntax and lexical/conceptual-semantics. We used
      ERPs to examine a violation paradigm involving "Negative Polarity Items" or NPIs
      (e.g., ever/any), which are sensitive to logical/truth-conditional properties of
      the environments in which they occur (e.g., presence/absence of negation in: John
      hasn't ever been to Paris, versus: John has *ever been to Paris). Previous
      studies examining similar types of contrasts found a mix of effects on familiar
      ERP components (e.g., LAN, N400, P600). We argue that their experimental designs
      and/or analyses were incapable of separating which effects are connected to NPI
      licensing violations proper. Our design enabled statistical analyses teasing
      apart genuine violation effects from independent effects tied solely to
      lexical/contextual factors. Here unlicensed NPIs elicited a late P600 followed in
      onset by a late left anterior negativity (or "L-LAN"), an ERP profile which has
      also appeared elsewhere in studies targeting logical semantics. Crucially,
      qualitatively distinct ERP-profiles emerged for syntactic and conceptual semantic
      violations which we also tested here. We discuss how these findings may be linked
      to previous findings in the ERP literature. Apart from methodological
      recommendations, we suggest that the study of logical semantics may aid advancing
      our understanding of the underlying neurocognitive etiology of ERP components.

PMID- 20138066
TI  - Opposite effects of alcohol in regulating stress-induced changes in body weight
      between the two mouse lines with enhanced or low opioid system activity.
AB  - Considering the involvement of the opioid system in alcoholism, depression and
      metabolism - known risk factors in human obesity, we studied the effects of
      chronic mild stress (CMS) and alcohol intake on body weight in two mouse lines
      selected for high (HA-high analgesia) or low (LA-low analgesia) swim stress
      induced analgesia. In comparison to LA mice, HA mice exhibit an upregulation of
      opioid receptor system function, different depression-like behavior and reduced
      energy expenditure in stress. LA animals showed enhanced basal and CMS-induced
      alcohol drinking versus HA. Now we report different effects of alcohol under no
      stress (control) and CMS conditions on food intake and body weight between the
      lines. CMS in animals with no access to alcohol increased body weight in both HA
      and LA mice, with no effect of CMS on food intake in either line and without
      differences between the lines. In LA mice alcohol reduced body weight under both
      conditions although significantly more under the control than CMS conditions. In
      contrast, in HA mice alcohol increased body weight more under the CMS than under
      control conditions. The results suggest that opioid system may modulate effects
      of alcohol on stress -induced changes in body weight.

PMID- 20138067
TI  - Oral sensory and cephalic hormonal responses to fat and non-fat liquids in
      bulimia nervosa.
AB  - Sensory evaluation of food involves endogenous opioid mechanisms. Bulimics
      typically limit their food choices to low-fat "safe foods" and intermittently
      lose control and binge on high-fat "risk foods". The aim of this study was to
      determine whether the oral sensory effects of a fat versus a non-fat milk product
      (i.e., traditional versus non-fat half-and-half) resulted in different subjective
      and hormonal responses in bulimic women (n=10) compared with healthy women
      (n=11). Naltrexone (50mg PO) or placebo was administered 1h before, and blood
      sampling began 30 min prior to and 29 min after, a 3 min portion controlled
      modified sham-feeding trial. Following an overnight fast, three morning trials
      (fat, naltrexone; fat, placebo; and non-fat, placebo) were administered in a
      random double-blind fashion separated by at least 3 days. Overall, there were no
      differences between Fat and Non-Fat trials. Hunger ratings (p<0.001) and
      pancreatic polypeptide levels (p<0.05) were higher for bulimics at baseline.
      Bulimics also had overall higher ratings for nausea (p<0.05), fatty taste
      (p<0.01), and fear of swallowing (p<0.005). Bulimics had approximately 40% higher
      total ghrelin levels at all time points (p<0.001). Hormones and glucose levels
      were not altered by the modified sham-feeding paradigm. Naltrexone, however,
      resulted in an overall increase in blood glucose and decrease in ghrelin levels
      in both groups (p<0.05, for both). These data suggest that bulimic women have
      different orosensory responses that are not influenced by opioid receptor
      antagonism, evident in hormonal responses, or dependent on the fat content of a
      similarly textured liquid.

PMID- 20138068
TI  - Opponent recognition and social status differentiate rapid neuroendocrine
      responses to social challenge.
AB  - Individual social status discriminates rapid neuroendocrine responses to non
      social stress in male Anolis carolinensis, but whether such status-influenced
      reactions are retained in response to subsequent social stress is unknown.
      Dominant and subordinate males modify their behavioral responses to social
      challenge according to familiarity of the opponent, suggesting that accompanying
      neuroendocrine responses may differ according to opponent recognition despite
      social rank. We examined endocrine and neurochemical correlates of prior social
      status and opponent recognition during the opening stages of social challenge.
      Male pairs interacted and established dominant/subordinate status, followed by 3
      days separation. Subsequently, subjects were paired with either the same opponent
      or an unfamiliar male according to rank (dominant with subordinate). After 90 s
      of social exposure, subjects were caught and brains and plasma collected for
      measurement of circulating corticosterone and limbic monoamines. Controls
      included pairs experiencing just one 90 s encounter plus a group of non
      interacting subjects. Opponent recognition differentiated status-influenced
      responses, such that dominant lizards paired with familiar subordinate opponents
      had increased hippocampal dopamine and epinephrine, but showed increased plasma
      corticosterone and ventral tegmental area (VTA) norepinephrine when challenged
      with an unfamiliar opponent. Subordinate lizards encountering familiar opponents
      also had increased corticosterone, along with decreased hippocampal dopamine and
      increased VTA epinephrine, but showed no changes in response to an unfamiliar
      opponent. Such plasticity in status-influenced rapid neuroendocrine responses
      according to opponent recognition may be necessary for facilitating production of
      behavioral responses adaptive for particular social contexts, such as
      encountering a novel versus familiar opponent.

PMID- 20138069
TI  - Prenatal flavor exposure affects growth, health and behavior of newly weaned
      piglets.
AB  - Young animals can learn about flavors from the maternal diet that appear in the
      amniotic fluid and mother's milk, which may reduce neophobia for similarly
      flavored food types at weaning. Flavor learning may be beneficial for piglets,
      which after the rather abrupt weaning in pig husbandry frequently show a period
      of anorexia, reduced health, and stress-induced behaviors. We investigated the
      effects of pre- and postnatal flavor exposure through the maternal diet on
      acceptance of a similarly flavored food and subsequent growth, health and
      behavior of newly weaned piglets. Sows were offered anise-flavored (F) or control
      (C) food during late gestation. Piglets were cross-fostered after birth, with
      each sow fostering 5 piglets from an F sow and 5 from a C sow. During lactation,
      sows were offered F or C food, resulting in FF, CF, FC and CC piglets. Piglets
      were weaned on day 25 and were given both control and flavored food for two weeks
      using a double food choice approach. The flavored food was not preferred. Yet,
      prenatally exposed animals showed a higher food intake and a higher body weight
      in the first days after weaning, and a lower occurrence of diarrhoea than non
      exposed piglets. Prenatal exposure also increased the latency to fight, and
      reduced oral manipulation of pen mates and mounting during the first two weeks
      after weaning. Prenatal exposure, but not postnatal exposure alone, to anisic
      flavor through the maternal diet reduced weaning-associated problems in piglets
      and enhanced their health and welfare in the period after weaning.

PMID- 20138070
TI  - Environmental enrichment enhances delayed-type hypersensitivity in both short-
      and long-day Siberian hamsters.
AB  - Darwinian fitness reflects trade-offs between reproduction and survival.
      Mechanisms have evolved in small nontropical mammals and birds to maximize
      reproductive output during the summer when thermoregulatory demands are
      relatively low and food is abundant and to shunt energy to processes that
      presumably increase the odds of survival during the winter when thermoregulatory
      demands are high and food is scarce. In order to predict the onset of winter,
      many seasonally-breeding mammals use day length (photoperiod) information.
      Seasonal adjustments of immune responses may be one mechanism to enhance
      survival; short days enhance cell-mediated immune function in seasonally-breeding
      rodents. The goal of the present study was to determine whether delayed-type
      hypersensitivity in hamsters is constrained or if photoperiod merely establishes
      a baseline level of immune response that can then be fined tuned by other
      environmental conditions. To test this, we used environmental enrichment, a
      manipulation that enhances many aspects of immune function. Hamsters were
      assigned to either long or short photoperiods and further assigned into either
      singly-housed or environmentally-enriched cages. After 10 weeks of concurrent
      photoperiod and housing treatment, delayed-type hypersensitivity (DTH) was
      induced. Although short days enhanced DTH responses compared with long days,
      environmental enrichment enhanced swelling responses in both short days and long
      days, suggesting that even during potential energetic bottlenecks or during
      maximal reproductive investment, hamsters can modulate their investment in immune
      function.

PMID- 20138071
TI  - Conspecific presence affects the physiology and behaviour of developing trout.
AB  - Interactions between conspecifics during embryonic development have the potential
      to influence phenotypic traits of individuals, with social interaction being
      particularly important for the realisation of normal behaviours. Here, the effect
      of increasing numbers of conspecifics (from isolation to groups of 20, 50, 100
      and 200) on the physiology and behaviour of developing trout was investigated
      with the hypothesis that a) conspecific presence would alter physiological
      processes and b) that development in the absence of conspecifics would affect
      subsequent behavioural performance. During development, mass, oxygen consumption,
      sodium uptake and ammonia excretion rates were measured at a variety of time
      points from fertilisation to after hatching. After first feeding, behaviour of
      individuals raised in social isolation was compared to behaviour of juvenile fish
      raised in social groups. Embryos and larvae raised in social isolation had lower
      oxygen consumption rates, lower sodium uptake rates and higher ammonia excretion
      rates compared to those raised in groups. Social isolation delayed the response
      of a juvenile fish to its own mirror image but did not affect the probability of
      it winning a paired encounter with an individual raised in a social environment.
      In conclusion, the presence of conspecifics alters physiological processes during
      trout embryo and larval development and subsequent social behaviours of
      juveniles.

PMID- 20138072
TI  - Impact of acute sleep restriction on cortisol and leptin levels in young women.
AB  - Sleep restriction alters hormone patterns and appetite in men, but less is known
      about effects on women. We assessed effects of overnight sleep restriction on
      cortisol and leptin levels and on appetite in young women. Participants' baseline
      sleep duration and eating habits were monitored for a week before the study.
      Salivary cortisol and leptin were sampled from fifteen healthy women (aged 18-25)
      during two consecutive days: first after a 10h overnight sleep opportunity
      (Baseline day) and then after a night including only 3h sleep (Post sleep
      restriction day). Participants also completed appetite questionnaires on both
      days. Sleep restriction significantly reduced morning cortisol levels (p=0.02),
      elevated morning leptin levels (p=0.04), elevated afternoon/evening cortisol area
      under the curve values (p=0.008), and slowed the decline in cortisol
      concentration during the day (p=0.04). Hunger and craving scores did not differ
      significantly between days. A single night of restricted sleep affected cortisol
      rhythms and morning leptin levels in young women.

PMID- 20138073
TI  - Role of dairy beverages in the diet.
AB  - The U.S. Dietary Guidelines for Americans recommends 3 cups of low fat milk or
      equivalent daily for most calorie levels [1]. Milk provides over 10% of the
      requirement for calcium, vitamin D, magnesium, phosphorus, potassium, riboflavin,
      protein, and carbohydrates for most people. Obtaining adequate intakes of
      calcium, potassium, and magnesium without milk in the diet requires effort. Milk
      has bioactive ingredients that may play unique roles in health. Benefits of dairy
      consumption are associated with reduced risk of low bone mass, stroke, metabolic
      syndrome, and some cancers. Concerns over milk consumption have focused on
      saturated fats historically. More research is needed to resolve potential
      concerns of milk consumption and risk of several disorders including ovarian
      cancer and soft tissue calcification.

PMID- 20138074
TI  - Brain distribution of genes related to changes in locomotor activity.
AB  - The relationship between genes and behavior, and particularly the hyperactive
      behavior, is clearly not linear nor monotonic. To address this problem, a
      database of the locomotor behavior obtained from thousands of mutant mice has
      been previously retrieved from the literature. Data showed that the percent of
      genes in the genome related to locomotor hyperactivity is probably more than
      1.56%. These genes do not belong to a single neurotransmitter system or
      biochemical pathway. Indeed, they are probably required for the correct
      development of a specific neuronal network necessary to decrease locomotor
      activity. The present paper analyzes the brain expression pattern of the genes
      whose deletion is accompanied by changes in locomotor behavior. Using literature
      data concerning knockout mice, 46 genes whose deletion was accompanied by
      increased locomotor behavior, 24 genes related to decreased locomotor behavior
      and 23 genes not involved in locomotor behavior (but important for other brain
      functions) have been identified. These three groups of genes belonged to
      overlapping neurotransmitter systems or cellular functions. Therefore, we
      postulated that a better predictor of the locomotor behavior resulting from gene
      deletion might be the brain expression pattern. To this aim we correlated the
      brain expression of the genes and the locomotor activity resulting from the
      deletion of the same genes, using two databases (Allen Brain Atlas and SymAtlas).
      The results showed that the deletion of genes with higher expression level in the
      brain had higher probability to be accompanied by increased behavioral activity.
      Moreover the genes that were accompanied by locomotor hyperactivity when deleted,
      were more expressed in the cerebral cortex, amygdala and hippocampus compared to
      the genes unrelated to locomotor activity. Therefore, the prediction of the
      behavioral effect of a gene should take into consideration its brain
      distribution. Moreover, data confirmed that genes highly expressed in the brain
      are more likely to induce hyperactivity when deleted. Finally, it is suggested
      that gene mutations linked to specific behavioral abnormalities (e.g.
      inattention) might probably be associated to hyperactivity if the same gene has
      elevated brain expression.

PMID- 20138075
TI  - Post-ingestive signals and satiation of water and sodium intake of male rats.
AB  - This study investigated the role of post-ingestive signals in the satiation of
      thirst or salt appetite. Post-ingestive signals, defined as those arising from
      the passage of fluid into the duodenum and proximal jejunum, were manipulated by
      implanting rats with gastric fistulas. After recovery, rats were water deprived
      and the following day gastric fistulas were opened (sham-drinking) or closed
      (control). Deprivation-induced thirst significantly increased water intake with
      sham-drinking rats consuming four-fold more than controls after 120 min access.
      Subsequently, rats were given sodium deficient chow for 48 h and the next day
      were administered furosemide and urine was collected. Twenty-four hours later,
      gastric fistulas were manipulated and rats were given water and 0.5M NaCl and
      intakes were measured. After 120 min of access, rats were sacrificed and plasma
      sodium (pNa) and plasma-renin-activity (PRA) were measured. Furosemide resulted
      in a loss of 2.2 mEq of sodium in urine and sham-drinking rats consumed
      significantly more water and 0.5M NaCl when compared to controls. At 120 min sham
      drinking rats consumed 7.5 mEq of sodium nearly twice that of controls but had
      significantly lower pNa and significantly increased PRA. Interestingly, the ratio
      of water to 0.5M NaCl intake was similar in both groups, with each making a
      mixture of approximately 0.25 M NaCl. The results suggest that post-ingestive
      signals are necessary for the satiation of thirst and salt appetite.

PMID- 20138076
TI  - Litter size is negatively correlated with corticosterone levels in weanling and
      juvenile laboratory rats.
AB  - An animal's environment during early life can strongly affect its physiological
      development. For example, litter size, i.e. the number of litter siblings, has
      been previously shown to strongly affect early growth in many small mammal
      species including laboratory rats. In the present study we tested whether
      natural, unmanipulated litter size is also associated with differences in stress
      hormone levels in young Long-Evans laboratory rats. We found a negative
      correlation between serum corticosterone (CORT) concentrations and litter size
      during two different stages of juvenile life. On postnatal day 17, shortly before
      weaning, this relationship was apparent with respect to basal CORT values. On day
      33, however, two weeks after weaning, we found this relationship only when
      animals were challenged by a 10-min test on an elevated plus maze, but not in
      control animals (basal values). Although the physiological basis of these
      differences is not clear, we discuss two main, not mutually exclusive
      possibilities: (a) delayed maturation of the HPA axis in typically lower body
      mass pups of large litters, and (b) that such pups, encountering greater
      competition for maternal resources, adjust to this presumably more stressful
      developmental environment by down-regulating responsiveness of the HPA axis. In
      conclusion, our study provides evidence that a naturally varying feature of the
      developmental environment of many altricial mammals - number of littermates - may
      contribute to individual differences in stress-related physiology. Furthermore,
      it suggests the need to consider litter-size effects when investigating
      differences in animals' stress responses.

PMID- 20138077
TI  - Tissue selectivity and potential clinical applications of trenbolone (17beta
      hydroxyestra-4,9,11-trien-3-one): A potent anabolic steroid with reduced
      androgenic and estrogenic activity.
AB  - Recently, the development of selective androgen receptor modulators (SARMs) has
      been suggested as a means of combating the deleterious catabolic effects of
      hypogonadism, especially in skeletal muscle and bone, without inducing the
      undesirable androgenic effects (e.g., prostate enlargement and polycythemia)
      associated with testosterone administration. 17beta-Hydroxyestra-4,9,11-trien-3
      one (trenbolone; 17beta-TBOH), a synthetic analog of testosterone, may be capable
      of inducing SARM-like effects as it binds to androgen receptors (ARs) with
      approximately three times the affinity of testosterone and has been shown to
      augment skeletal muscle mass and bone growth and reduce adiposity in a variety of
      mammalian species. In addition to its direct actions through ARs, 17beta-TBOH may
      also exert anabolic effects by altering the action of endogenous growth factors
      or inhibiting the action of glucocorticoids. Compared to testosterone, 17beta
      TBOH appears to induce less growth in androgen-sensitive organs which highly
      express the 5alpha reductase enzyme (e.g., prostate tissue and accessory sex
      organs). The reduced androgenic effects result from the fact that 17beta-TBOH is
      metabolized to less potent androgens in vivo; while testosterone undergoes tissue
      specific biotransformation to more potent steroids, dihydrotestosterone and
      17beta-estradiol, via the 5alpha-reductase and aromatase enzymes, respectively.
      Thus the metabolism of 17beta-TBOH provides a basis for future research
      evaluating its safety and efficacy as a means of combating muscle and bone
      wasting conditions, obesity, and/or androgen insensitivity syndromes in humans,
      similar to that of other SARMs which are currently in development.

PMID- 20138079
TI  - Interspecies differences in metabolism of arsenic by cultured primary
      hepatocytes.
AB  - Biomethylation is the major pathway for the metabolism of inorganic arsenic (iAs)
      in many mammalian species, including the human. However, significant interspecies
      differences have been reported in the rate of in vivo metabolism of iAs and in
      yields of iAs metabolites found in urine. Liver is considered the primary site
      for the methylation of iAs and arsenic (+3 oxidation state) methyltransferase
      (As3mt) is the key enzyme in this pathway. Thus, the As3mt-catalyzed methylation
      of iAs in the liver determines in part the rate and the pattern of iAs metabolism
      in various species. We examined kinetics and concentration-response patterns for
      iAs methylation by cultured primary hepatocytes derived from human, rat, mice,
      dog, rabbit, and rhesus monkey. Hepatocytes were exposed to [(73)As]arsenite
      (iAs(III); 0.3, 0.9, 3.0, 9.0 or 30 nmol As/mg protein) for 24 h and radiolabeled
      metabolites were analyzed in cells and culture media. Hepatocytes from all six
      species methylated iAs(III) to methylarsenic (MAs) and dimethylarsenic (DMAs).
      Notably, dog, rat and monkey hepatocytes were considerably more efficient
      methylators of iAs(III) than mouse, rabbit or human hepatocytes. The low
      efficiency of mouse, rabbit and human hepatocytes to methylate iAs(III) was
      associated with inhibition of DMAs production by moderate concentrations of
      iAs(III) and with retention of iAs and MAs in cells. No significant correlations
      were found between the rate of iAs methylation and the thioredoxin reductase
      activity or glutathione concentration, two factors that modulate the activity of
      recombinant As3mt. No associations between the rates of iAs methylation and As3mt
      protein structures were found for the six species examined. Immunoblot analyses
      indicate that the superior arsenic methylation capacities of dog, rat and monkey
      hepatocytes examined in this study may be associated with a higher As3mt
      expression. However, factors other than As3mt expression may also contribute to
      the interspecies differences in the hepatocyte capacity to methylate iAs.

PMID- 20138078
TI  - The interplay between bioactive sphingolipids and steroid hormones.
AB  - Steroid hormones regulate various physiological processes including development,
      reproduction, and metabolism. These regulatory molecules are synthesized from
      cholesterol in endocrine organs - such as the adrenal glands and gonads - via a
      multi-step enzymatic process that is catalyzed by the cytochrome P450 superfamily
      of monooxygenases and hydroxysteroid dehydrogenases. Steroidogenesis is induced
      by trophic peptide hormones primarily via the activation of a cAMP/protein kinase
      A (PKA)-dependent pathway. However, other signaling molecules, including
      cytokines and growth factors, control the steroid hormone biosynthetic pathway.
      More recently, sphingolipids, including ceramide, sphingosine-1-phosphate, and
      sphingosine, have been found to modulate steroid hormone secretion at multiple
      levels. In this review, we provide a brief overview of the mechanisms by which
      sphingolipids regulate steroidogenesis. In addition, we discuss how steroid
      hormones control sphingolipid metabolism. Finally, we outline evidence supporting
      the emerging role of bioactive sphingolipids in various nuclear processes and
      discuss a role for nuclear sphingolipid metabolism in the control of gene
      transcription.

PMID- 20138080
TI  - Proteomic analysis of host responses to Marek's disease virus infection in
      spleens of genetically resistant and susceptible chickens.
AB  - Resistance to Marek's disease (MD) in chickens is genetically regulated and there
      are lines of chickens with differential susceptibility or resistance to this
      disease. The present study was designed to study comparative changes in the
      spleen proteomes of MD-susceptible B19 and MD-resistant B21 chickens in response
      to MDV infection. Spleen proteomes were examined at 4, 7, 14 and 21 days post
      infection (d.p.i.) using two-dimensional gel electrophoresis and subsequently the
      protein spots were identified by one-dimensional liquid chromatography
      electrospray ionization tandem mass spectrometry (1D LC ESI MS/MS). On average,
      there were 520+/-27 distinct protein spots on each gel and 1.6+/-0.7% of the
      spots differed quantitatively in their expression (p< or =0.05 and fold change >
      or =2) between infected B19 and B21 chickens. There was one spot at 4d.p.i. and
      three spots each at the rest of the time points, which had a qualitative
      difference in expression. Most of the differentially expressed proteins at 4 and
      7d.p.i. displayed increased expression in B21 chickens; conversely the
      differentially expressed proteins at 14 and 21d.p.i. showed an increase in
      expression in B19 chickens. The differentially expressed proteins identified in
      the present study included antioxidants, molecular chaperones, proteins involved
      in the formation of cytoskeleton, protein degradation and antigen presentation,
      signal transduction, protein translation and elongation, RNA processing and cell
      proliferation. These findings shed light on some of the underlying processes of
      genetic resistance or susceptibility to MD.

PMID- 20138081
TI  - Invasive fusariosis in patients with hematologic malignancies at a cancer center:
      1998-2009.
AB  - BACKGROUND: Fusarium species cause severe infections in patients with hematologic
      malignancies. Few data are available concerning the outcome of fusariosis in the
      era of the expanding antifungal armamentarium. METHODS: We retrospectively
      identified patients with hematologic malignancy and positive cultures for
      Fusarium species at the MDACC (1998-2009). The diagnosis of proven or probable
      fusariosis was made according to modified EORTC/MSG criteria. RESULTS: Forty-four
      cases (75% proven) were identified over study period. Most (71%) patients had
      uncontrolled hematological malignancy and 21 patients (47%) received
      hematopoietic stem cell transplantation (85% allogeneic). Most patients (82%)
      were neutropenic at diagnosis (75% < 100/mm(3)). Patients had overlapping
      clinical syndromes: sinus 27%, pulmonary 75%, skin 68%, fungemia 36% and
      disseminated infection 70%. Bacterial (54%), fungal (36%) and viral (27%) co
      infections were common. Most patients (84%) received combination therapy
      (typically a lipid formulation of amphotericin B and a triazole) with a mean
      duration of 28 days. Mortality at 12 weeks was 66%; 50% of deaths were
      attributable to Fusarium. Factors associated with increased likelihood of death
      at 12 weeks, included albumin <3.5 mg/dL, fungemia, and ICU admission; neutrophil
      recovery and fusariosis limited to skin were associated with improved survival (P
      < 0.05). Fungemia with Fusarium spp (OR 15.9; 1.1-231; P = 0.042) was the only
      risk factor independently associated with 12-week mortality with only 1/17 (6%)
      of patients still alive at 12 weeks. CONCLUSIONS: Fusariosis, although uncommon,
      continues to have poor prognosis in neutropenic leukemic patients who present
      with fungemia.

PMID- 20138082
TI  - A novel screening method for influenza patients using a newly developed non
      contact screening system.
AB  - OBJECTIVES: In places of mass gathering, rapid infection screening prior to
      definite diagnosis is vital during the epidemic season of a novel influenza. In
      order to assess the possibility of clinical application of a newly developed non
      contact infection screening system, we conducted screening for influenza
      patients. MATERIALS AND METHODS: The system is operated by a screening program
      via a linear discriminant analysis using non-contact derived variables, i.e.,
      palmar pulse derived from a laser Doppler blood-flow meter, respiration rate
      determined by a 10-GHz microwave radar, and average facial temperature measured
      by thermography. The system was tested on 57 seasonal influenza (2008-2009)
      patients (35.7 degrees C < or = body temperature < or = 38.3 degrees C, 19-40
      years) and 35 normal control subjects (35.5 degrees C < or = body temperature <
      or = 36.9 degrees C, 21-35 years) at the Japan Self-defense Forces Central
      Hospital. RESULTS: A significant linear discriminant function (p < 0.001) was
      determined to distinguish the influenza group from the control group (Mahalanobis
      D-square = 6.5, classification error rate > 10%). The system had a positive
      predictive value (PPV) of 93%, which is higher than the PPV value (PPV < or =
      65.4%) reported in the recent summary of studies using only thermography
      performed mainly in hospitals. CONCLUSIONS: The proposed system appears promising
      for application in accurate screening for influenza patients at places of mass
      gathering.

PMID- 20138083
TI  - Novel use of X-ray micro computed tomography to image rat sciatic nerve and
      integration into scaffold.
AB  - This paper describes how specimens of nervous tissue can be prepared for
      successful imaging in X-ray Micro Computed Tomography (microCT), and how this
      method can be used to study the integration of nervous tissue into a polymeric
      scaffold. The sample preparation involves staining the biological tissue with
      osmium tetroxide to increase its X-ray attenuation, and a technique for
      maintaining the specimen in a moist environment during the experiment to prevent
      drying and shrinkage. Using this method it was possible to observe individual
      nerve fascicles and their relationship to the 3-D tissue structure. A scaffold
      supporting a regenerated sciatic nerve was similarly stained to distinguish the
      nervous tissue from the scaffold, and to observe how the nerve grew through a 2.5
      mm long, 100 microm x 100 microm cross-section channel polyimide array.
      Furthermore, blood vessels could be identified in these images, and it was
      possible to monitor how a large proximal blood vessel split through the channel
      scaffold and proceeded down individual channels. This paper explains how microCT
      is a useful tool both for studying the location and extent of growth into a
      polymeric scaffold, and for determining whether the regenerated tissue has blood
      supply.

PMID- 20138084
TI  - Selection of high affinity peptide ligands for detection of circulating
      antibodies in neurocysticercosis.
AB  - Neurocysticercosis (NC), caused by Taenia solium, is the most common infection
      caused by helminthes of the human central nervous system. In this study, a random
      peptide phage display library was used to isolate peptide ligands as potential
      markers for neurocysticercosis diagnosis, because occurrence of cross-reactions
      with other helminthes species in the current used markers. We selected different
      peptides using IgG purified from pooled sera of neurocysticercosis patients. To
      investigate the diagnostic potential of recombinant peptides, we have tested
      different panels of serum samples by Phage-ELISA, and 10 phage clones strongly
      bound to the anti-T. solium IgGs in NC sera, with an accuracy range from 84.2% to
      95%. The phage clones, NC(4)1 and NC(2)8, presented the highest sensitivity and
      specificity (100%), respectively, and most important, some phage clones did not
      react with patients' sera from Echinococcus granulosus infected patients. The
      validation with a competitive ELISA assay demonstrated that the selected phages
      could mimic T. solium epitopes and bind specifically to the pool of NC sera.
      Finally, the two recombinant antigens may become potential biomarkers for
      serodiagnosis of NC, and the Phage-ELISA demonstrated to be a very good assay,
      being reproducible, simple, fast, and low-cost due to its production through
      Escherichia coli culture, allowing a high throughput screening of NC.

PMID- 20138085
TI  - Immunogenic properties of chimeric potato virus X particles displaying the
      hepatitis C virus hypervariable region I peptide R9.
AB  - The immunogenic properties of chimeric potato virus X (PVX) particles engineered
      to display the synthetic R9 peptide have been evaluated. The R9 peptide is a
      consensus sequence derived from diverse variants of the hypervariable region 1
      from the hepatitis C virus (HCV) envelope protein E2. Two different constructs
      were designed, with the R9 peptide expressed either as an indirect fusion via the
      ribosomal skip 2A (PVX(R9-2A)CP) sequence or as a direct PVX coat protein fusion
      (PVX(R9)CP). Systemic infection of Nicotiana benthamiana plants was only achieved
      with PVX(R9-2A)CP constructs, and the presence of the R9 peptide was detected in
      extracts from these plants by ELISA, Western blot and electron microscopy using
      specific anti-R9 antibodies. The virus particles were recovered at yields of up
      to 125mg/kg from leaf material. BALB/c mice immunized with purified PVX(R9-2A)CP
      particles developed specific anti-R9 IgG titers of up to 1:50,000. Monoclonal
      anti-R9 antibodies were obtained from the spleen of a mouse immunized with PVX(R9
      2A)CP particles and characterized by Western blot and electron microscopy. Sera
      from patients infected chronically with HCV were found to react specifically with
      PVX(R9-2A)CP particles in 35% of cases.

PMID- 20138086
TI  - Multiplex real-time RT-PCR for detection of Wheat streak mosaic virus and
      Triticum mosaic virus.
AB  - Wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) are widespread
      throughout the southwestern Great Plains states. When using conventional
      diagnostics such as enzyme-linked immunosorbent assays (ELISA), these two viruses
      are commonly found together in infected wheat samples. Methods for molecular
      detection have been developed for wheat viral pathogens, but until recently no
      multiplex method for detection of both WSMV and TriMV within a single sample was
      available. Therefore, the objective of this study was to develop a multiplex real
      time PCR technique for detection of both pathogens within a single plant sample.
      Specific primers and probe combinations were developed for detection of WSMV and
      TriMV, single and multiple reactions were run simultaneously to detect any loss
      in sensitivity during the multiplex reaction, as well as any cross-reaction with
      other common wheat viruses. The multiplex reaction was successful in detection of
      both pathogens, with little difference between single and multiplex reactions,
      and no cross-reaction was found with other common wheat viruses. This multiplex
      technique not only will be useful for diagnostic evaluations, but also as a
      valuable tool for ecological and epidemiology studies, and investigations of
      host/pathogen interactions, especially when the host is infected with both
      pathogens.

PMID- 20138087
TI  - Development of an in vitro dual-chamber model of the female genital tract as a
      screening tool for epithelial toxicity.
AB  - Heterosexual transmission of human immunodeficiency virus (HIV-1) is the
      predominant mode of infection worldwide. However, the early steps of
      transepithelial infection still need to be clarified. Using epithelial cells,
      originating from the female genital tract, and peripheral blood mononuclear cells
      as subepithelial target cells, an in vitro dual-chamber model of the female
      genital tract was developed. Remarkably, an intact layer of some cell types (HEC
      1A, CaSki and Ect1) served as a protective barrier against cell-free but not
      against cell-associated HIV-1 that crossed the epithelial barrier through
      transmigration. Furthermore, dysfunctions of the epithelial layers were assessed
      by monitoring transepithelial electric resistance and transepithelial passage of
      FluoSpheres and HIV-1 after treatment with nonoxynol-9 (N-9). Most of the
      functional assays showed dysfunction of the epithelial barrier at lower
      concentrations compared to a widely used colorimetric toxicity assay (WST-1).
      Finally, N-9 treatment caused a significant increase in the production of
      interleukin-8 (IL-8) and macrophage inflammatory protein-3alpha (MIP-3alpha) and
      a decrease of Secretory Leukocyte Protease Inhibitor (SLPI) and Monocyte
      Chemotactic Protein-1 (MCP-1) in this model. In conclusion, this model is a
      useful tool to (1) study HIV-1 transmission mechanisms and (2) evaluate
      epithelial toxicity of candidate microbicides.

PMID- 20138088
TI  - RS-0406 arrests amyloid-beta oligomer-induced behavioural deterioration in vivo.
AB  - Clinically accessible compounds that arrest or reverse the effects of amyloid
      beta (Abeta) on progressively developing behavioural symptomatology and
      neuropathology in Alzheimer's disease (AD) have yet to become available. However,
      a viable strategy may be to target and neutralise soluble Abeta oligomers, which
      have been shown to mediate synaptic dysfunction and to produce cognitive deficits
      in the intact organism. Inhibiting the aggregation of Abeta is therapeutically
      attractive, as Abeta aggregation is a pathological event and pharmacological
      interventions targeting this are likely to have a non-toxic profile. A
      behavioural assay, the alternating-lever cyclic-ratio schedule, was used to
      assess the effect of Abeta oligomers and the non-peptide small molecule RS-0406
      in male Sprague-Dawley rats. RS-0406 has been shown to inhibit Abeta(1-42)
      fibrillogenesis and protect against Abeta(1-42)-induced cytotoxicity in primary
      hippocampal neurons. In the current study, RS-0406 ameliorated the adverse
      effects of secreted oligomers of human Abeta on behaviour and dose dependently
      reduced the behavioural effects of Abeta oligomers, with the highest dose,
      10microM, maintaining behaviour approximately at control levels. This effect
      appeared to be central; peripheral confounds having been extensively
      investigated. This is the first published report on the effects of RS-0406 in
      vivo and indicates that RS-0406 has potential as a pharmacotherapeutic
      intervention for behavioural deficits seen in the early stages of AD, and
      possibly as an intervention in the development of AD neuropathology. Indeed, an
      analogue of RS-0406 that could be administered peripherally might be a realistic
      candidate for the clinical treatment of AD.

PMID- 20138089
TI  - Morpho-functional asymmetry of the olfactory receptors of the honeybee (Apis
      mellifera).
AB  - Lateralization, i.e., the different functional specialisation of the left and
      right side of the brain, has been documented in many vertebrate species and,
      recently, in invertebrate species as well. In the Honeybee, Apis mellifera L.
      (Hymenoptera Apidae), it has been shown that short-term (<1h) recall of olfactory
      memories would be possible mainly from the right rather than from the left
      antenna. Here we confirmed this finding showing that recall of the olfactory
      memory 1h after training to associate (-)-linalool, a floral volatile compound,
      with a sugar reward, as revealed by the bee extending its proboscis when
      presented with the trained odour, was better when the odour was presented to the
      right rather than to the left antenna. We then measured the number of sensilla
      present on the left and right antenna by scanning electron microscopy. Results
      showed that putative olfactory sensilla (placodea, trichodea, basiconica) were
      significantly more abundant on the right antenna surface than on the left antenna
      surface, whereas sensilla not involved in olfaction (campaniformia, coeloconica
      and chaetica) tended to be more abundant on the left than on the right antenna
      surface.

PMID- 20138090
TI  - Circadian rhythm and suprachiasmatic nucleus alterations in the mouse model of
      mucopolysaccharidosis IIIB.
AB  - Mucopolysaccharidosis IIIB (MPSIIIB) is a lysosomal storage disease characterised
      by progressive central nervous system degeneration in patients, with death
      usually in the late teens. Serious behavioural problems have been reported in
      children at the early stages of the disease, such as hyperactivity and severe
      sleep disturbances, which suggest alterations in circadian rhythms. We
      investigated the circadian rhythm of locomotor activity of young and old MPSIIIB
      mice, under a 24-h light-dark (LD) cycle and under constant darkness (DD), and
      also examined neuropeptide expression in the suprachiasmatic nucleus (SCN), site
      of the principal biological pacemaker. We show that MPSIIIB mice have higher
      activity levels during the light (resting) phase of the LD cycle, together with
      weaker circadian rhythms, and a longer active phase due to a late peak of
      activity, in both LD and DD. In addition, young MPSIIIB mice showed shorter phase
      delays in response to a light pulse in DD. Increased lysosomal storage,
      neuroinflammation and changes in the expression of Arginine Vasopressin and
      Vasointestinal Polypeptide, two circadian neuropeptides, were observed in the
      SCN, which may be in part responsible for the changes in circadian behaviour
      observed in MPSIIIB mice. These findings suggest an alteration of the circadian
      system in MPSIIIB mice, and may inform better clinical management of circadian,
      sleep and behavioural disturbances in patients with MPSIII.

PMID- 20138091
TI  - An internal sequence targets Trypanosoma brucei triosephosphate isomerase to
      glycosomes.
AB  - In kinetoplastid protists, glycolysis is compartmentalized in glycosomes,
      organelles belonging to the peroxisome family. The Trypanosoma brucei glycosomal
      enzyme triosephosphate isomerase (TPI) does not contain either of the two
      established peroxisome-targeting signals, but we identified a 22 amino acids long
      fragment, present at an internal position of the polypeptide, that has the
      capacity to route a reporter protein to glycosomes in transfected trypanosomes,
      as demonstrated by cell-fractionation experiments and corroborating
      immunofluorescence studies. This polypeptide-internal routing information seems
      to be unique for the sequence of the trypanosome enzyme: a reporter protein fused
      to a Saccharomyces cerevisiae peptide containing the sequence corresponding to
      the 22-residue fragment of the T. brucei enzyme, was not targeted to glycosomes.
      In yeasts, as in most other organisms, TPI is indeed exclusively present in the
      cytosol. These results suggest that it may be possible to develop new
      trypanocidal drugs by targeting specifically the glycosome import mechanism of
      TPI.

PMID- 20138092
TI  - Biogenesis of membrane bound respiratory complexes in Escherichia coli.
AB  - Escherichia coli is one of the preferred bacteria for studies on the energetics
      and regulation of respiration. Respiratory chains consist of primary
      dehydrogenases and terminal reductases or oxidases linked by quinones. In order
      to assemble this complex arrangement of protein complexes, synthesis of the
      subunits occurs in the cytoplasm followed by assembly in the cytoplasm and/or
      membrane, the incorporation of metal or organic cofactors and the anchoring of
      the complex to the membrane. In the case of exported metalloproteins, synthesis,
      assembly and incorporation of metal cofactors must be completed before
      translocation across the cytoplasmic membrane. Coordination data on these
      processes is, however, scarce. In this review, we discuss the various processes
      that respiratory proteins must undergo for correct assembly and functional
      coupling to the electron transport chain in E. coli. Targeting to and
      translocation across the membrane together with cofactor synthesis and insertion
      are discussed in a general manner followed by a review of the coordinated
      biogenesis of individual respiratory enzyme complexes. Lastly, we address the
      supramolecular organization of respiratory enzymes into supercomplexes and their
      localization to specialized domains in the membrane.

PMID- 20138093
TI  - Development of pooled suppression subtractive hybridization to analyze the
      pangenome of Staphylococcus aureus.
AB  - We describe the development and application of a Pooled Suppression Subtractive
      Hybridization (PSSH) method to describe differences between the genomic content
      of a pool of clinical Staphylococcus aureus isolates and a sequenced reference
      strain. In comparative bacterial genomics, Suppression Subtractive Hybridization
      (SSH) is normally utilized to compare genomic features or expression profiles of
      one strain versus another, which limits its ability to analyze communities of
      isolates. However, a PSSH approach theoretically enables the user to characterize
      the entirety of gene content unique to a related group of isolates in a single
      reaction. These unique fragments may then be linked to individual isolates
      through standard PCR. This method was applied to examine the genomic diversity
      found in pools of S.aureus isolates associated with complicated bacteremia
      infections leading to endocarditis and osteomyelitis. Across four pools of 10
      isolates each, four hundred and twenty seven fragments not found in or
      significantly divergent from the S. aureus NCTC 8325 reference genome were
      detected. These fragments could be linked to individual strains within its pool
      by PCR. This is the first use of PSSH to examine the S. aureus pangenome. We
      propose that PSSH is a powerful tool for researchers interested in rapidly
      comparing the genomic content of multiple unstudied isolates.

PMID- 20138094
TI  - An oligonucleotide microarray to characterize multidrug resistant plasmids.
AB  - Many of the Enterobacteriaceae carry multiple drug resistance (MDR) genes on
      large plasmids of replicon type Inc A/C and Inc H1. It is important to understand
      the transmission of these MDR plasmids because the genes they carry can affect
      the outcome of antimicrobial therapy. The aim of this study was to design a
      microarray with oligonucleotide probes for every gene in the six Inc A/C and one
      Inc H1 plasmids of interest while representing all redundant sequences only once.
      The microarray is printed in triplicate with 493 unique oligonucleotide probes 70
      nucleotides in length. Salmonella enterica and Escherichia coli control strains
      and test plasmids (in the parent strain and transformed into a known E. coli
      background strain) were hybridized to the plasmid microarray. This hybridization
      arrays presents a rapid and cost effective method for high-density screening of
      isolates to evaluate the gene content of Inc A/C and H1 plasmids and will show
      how plasmids can change content with transmission.

PMID- 20138095
TI  - Antihistamine effects on prefrontal cortex activity during working memory process
      in preschool children: a near-infrared spectroscopy (NIRS) study.
AB  - Histamine H1 receptor antagonists (antihistamines) are widely used for the
      treatment of allergic disorders in young children. This study examined the
      effects of antihistamine on prefrontal cortex activity in preschool children
      using near-infrared spectroscopy (NIRS), an emerging brain-imaging method
      suitable for psychological experiments, especially in young children. We examined
      the changes of oxygenated hemoglobin concentration in the prefrontal cortex while
      children performed a spatial working memory task, 3h after taking a first
      generation antihistamine (ketotifen), second-generation antihistamine
      (epinastine), or placebo. Fifteen healthy preschool children (mean age, 5.5
      years) participated. Ketotifen significantly impaired behavioral performance and
      cortical activation at the lateral prefrontal cortex in the working memory task,
      compared with epinastine and placebo. There were no sedative effects on neural
      response or behavioral performance after epinastine administration. This paper
      demonstrates for the first time differential sedation effects of first- and
      second-generation antihistamines on brain hemodynamic response in young children.
      Also discussed is the utility of the NIRS technique in neuropsychopharmacological
      studies of children.

PMID- 20138096
TI  - Fluorescently labeled 1 nm thin nanomembranes.
AB  - Fluorescent labeling of self-assembled monolayers (SAMs) has a great potential
      for chemical and biotechnological sensing. However, its use is limited by the
      quenching of the fluorescence in the proximity of the conducting substrates. We
      show that this quenching can be overcome by the labeling of a cross-linked
      aromatic SAM (nanosheet) and its subsequent transfer onto a non-conducting
      substrate. We demonstrate the successful labeling of nanosheets with a
      fluorophore (tetramethylrhodamine) and its subsequent transfer to oxidized
      silicon, where they are detected by optical as well as fluorescence microscopy.
      Fluorescently labeled freestanding nanosheets, i.e. nanomembranes were obtained
      by a similar transfer of the nanosheets to TEM grids.

PMID- 20138097
TI  - Bioartificial pancreas microencapsulation and conformal coating of islet of
      Langerhans.
AB  - Type 1 diabetes has been successfully treated by transplanting islets of
      Langerhans (islets), endocrine tissue releasing insulin. Serious issues, however,
      still remain. The administration of immunosuppressive drugs is required to
      prolong graft functioning; however, side effects of their long-term use on
      recipients are not fully understood, and cell transplantation therapy without the
      use of immunosuppressive drugs is desired. To resolve these issues, the
      encapsulation of isles with a semi-permeable membrane, or bioartificial pancreas,
      has been attempted. Many groups have reported that it functions very well in
      small animal models. Few of the bioartificial pancreases, however, were applied
      to human patients and their clinical outcome was not clear. In this review, we
      address obstacles and overview new techniques to overcome these issues, such as
      conformal coating and islet enclosure with cells.

PMID- 20138098
TI  - Antimicrobial peptides of an anti-lipopolysaccharide factor, epinecidin-1, and
      hepcidin reduce the lethality of Riemerella anatipestifer sepsis in ducks.
AB  - Antimicrobial peptides (AMPs) are effective against a wide range of microbes, but
      still no research results have reported their use in duck disease therapy.
      Riemerella anatipestifer (RA) is a Gram-negative bacterium which infects ducks
      and causes very significant economic losses. The minimum inhibitory
      concentrations (MICs) of epinecidin-1 for the tested RA strains ranged 6.25
      50microg/ml, those of the SALF55-76 cyclic peptide ranged 12.5-25microg/ml, those
      of the SALF55-76 linear peptide ranged 6.25-25microg/ml, those of hepcidin TH1-5
      ranged 25-400microg/ml, and those of hepcidin TH2-3 ranged 100-400microg/ml. The
      antimicrobial activities of these peptides were confirmed by transmission
      electron microscopy which showed that RA disruption of the outer membrane brought
      about cell death. In addition, pretreatment, co-treatment, and post-treatment
      with peptides were all effective in promoting a significant decrease in duck
      mortality and decreasing the number of infectious bacteria. A quantitative RT-PCR
      was performed to survey levels of gene expressions of Mn superoxide dismutase in
      the brain, lipoprotein lipase in the liver, and H5 histone in the spleen induced
      in response to bacterial infection and an injection of the AMPs in experiments
      with the duck, Cairina moschata. Our results indicated that the rescue of ducks
      by the peptides and the behavior of the peptides, which was like an enhancer in
      immunology, may involve regulation of the expressions of these genes.
      Collectively, these peptides reduced the mortality in ducks during bacterial
      challenge, suggesting that AMPs have the potential to serve as therapeutic drugs
      for use against bacterial infectious diseases in ducks.

PMID- 20138099
TI  - Identification of potent 11mer glucagon-like peptide-1 receptor agonist peptides
      with novel C-terminal amino acids: Homohomophenylalanine analogs.
AB  - We report the identification of potent agonists of the Glucagon-Like Peptide-1
      Receptor (GLP-1R). These compounds are short, 11 amino acid peptides containing
      several unnatural amino acids, including (in particular) analogs of
      homohomophenylalanine (hhPhe) at the C-terminal position. Typically the
      functional activity of the more potent peptides in this class is in the low
      picomolar range in an in vitro cAMP assay, with one example demonstrating
      excellent in vivo activity in an ob/ob mouse model of diabetes.

PMID- 20138100
TI  - Beyond water channel: aquaporin-4 in adult neurogenesis.
AB  - Aquaporin-4 (AQP4) is a key molecule for maintaining water and ion homeostasis
      associated with neuronal activity in the central nervous system, but the roles of
      AQP4 in adult neurogenesis remain largely unexplored. Based on preliminary
      evidences over the past years, AQP4 appears to emerge as an important player
      regulating the multiple steps of adult neurogenesis. In this mini-review, we
      discuss the recent findings that reveal a specific functional role of AQP4 in
      regulating the adult neurogenesis, including proliferation of neural
      progenitors/neural stem cells, fate specification and differentiation, neuronal
      migration, and the potential mechanisms. Further studies on the regulation of
      AQP4 in promoting neurogenesis will lead to better understanding of the signaling
      mechanisms of adult neurogenesis and potentially provide an opportunity to
      develop AQP4 as new drug target for neurogenesis.

PMID- 20138101
TI  - Quantitative and statistical analysis of differences in sensitivity between Long
      Evans and Han/Wistar rats following long-term exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - In this study, differences in sensitivity between Long-Evans (L-E; dioxin
      sensitive) and Han/Wistar (H/W; dioxin resistant) rats following long-term
      exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were statistically and
      quantitatively investigated. Sensitivity differences were analyzed by comparing
      benchmark doses (BMDs) for the two strains considering a number of toxicological
      endpoints including data on body and organ weights, hepatic foci, hepatic CYP1A1
      induction, as well as tissue retinoid levels. Dose-response relationships for L-E
      and H/W rats, described by the Hill function, were assumed to be parallel, which
      was supported according to statistical analysis. It was concluded that L-E and
      H/W rats differed statistically in their response to TCDD treatment for most of
      the parameters investigated. Differences between the strains were most pronounced
      for hepatic foci; L-E rats were approximately 20-40 times more sensitive than H/W
      rats. For body and organ weight parameters, L-E rats were approximately 10-20
      times more sensitive than H/W rats. For retinoid parameters and hepatic CYP1A1
      induction, estimated differences between the strains were generally about 5-fold,
      and associated with a low uncertainty. In conclusion, the present study employs a
      dose-response modeling approach suitable for statistical evaluation of strain and
      species differences in sensitivity to chemical exposure. The study demonstrates
      quantitatively the differences in sensitivity between the L-E and H/W rat strains
      following long-term TCDD exposure.

PMID- 20138102
TI  - Hypothalamic glutamate levels following serotonergic stimulation: a pilot study
      using 7-Tesla magnetic resonance spectroscopy in healthy volunteers.
AB  - INTRODUCTION AND PURPOSE: Functional proton magnetic resonance spectroscopy (MRS)
      can be applied to measure pharmacodynamic effects of central nervous system (CNS)
      active drugs. The serotonin precursor 5-hydroxytryptophan (5-HTP), administered
      together with carbidopa and granisetron to improve kinetics and reduce adverse
      effects, acutely enhances central serotonergic neurotransmission and induces
      hypothalamus-pituitary-adrenal-(HPA) axis activation. We studied the hypothalamic
      levels of glutamate/glutamine (Glx), choline (Chol), N-acetyl-aspartate (NAA) and
      creatine using 7-Tesla (7T) MRS, and adrenocorticotropic hormone (ACTH) and
      cortisol in peripheral blood, after the administration of the 5-HTP function test
      in healthy volunteers. METHODS: A randomized, double blind, placebo-controlled,
      two-way cross-over study was performed in 12 healthy males with a 7day wash-out
      period. After administration of the oral 5-HTP function test, ACTH and cortisol
      were measured over 4h and MRS scans at 7T were performed every 30min over 3h
      measuring Glx:Creatine, Chol:Creatine and NAA:Creatine ratios. RESULTS: In the
      hypothalamus, the administration of 5-HTP had no effect on the average Glx, Chol
      or NAA levels over 180min but induced a significant decrease of Glx at 60min on
      post-hoc analysis. 5-HTP-induced significant ACTH release reaching an E(max) of
      60.2ng/L at 80min followed by cortisol with an E(max) of 246.4ng/mL at 110min.
      CONCLUSIONS: The reduction in hypothalamic Glx levels after serotonergic
      stimulation is compatible with activation of excitatory neurons in this region,
      which is expected to cause depletion of local glutamate stores. The hypothalamic
      MRS-response reached its maximum prior to subsequent increases of ACTH and
      cortisol, which support the functional relevance of hypothalamic Glx-depletion
      for activation of the HPA-axis. This exploratory study shows that MRS is capable
      of detecting neuronal activation following functional stimulation of a targeted
      brain area.

PMID- 20138103
TI  - Genotoxicity studies on fucoidan from Sporophyll of Undaria pinnatifida.
AB  - The sulfated seaweed extract, fucoidan, has anticoagulant, antithrombotic, and
      antiviral activities. Despite extensive work on the biological activities of
      fucoidan, detailed studies on the genotoxicity of fucoidan from Sporophyll of
      Undaria pinnatifida sources have not been tested before. The objective of this
      study was to investigate the genotoxicity effects of fucoidan extracted from
      Sporophyll of U. pinnatifida using a test battery of three different methods. In
      a reverse mutation assay using four Salmonella typhimurium strains and
      Escherichia coli, fucoidan did not increase the number of revertant colonies in
      any tester strain regardless of metabolic activation by S9 mix, and did not cause
      chromosomal aberration in short tests with S9 mix or in the continuous (24 h)
      test. A bone marrow micronucleus test in ICR mice dosed by oral gavage at doses
      up to 2000 mg/kg bw/day showed no significant or dose-dependent increases in the
      frequency of micronucleated polychromatic erythrocytes (MNPCE), and the high dose
      suppressed the ratio of polychromatic erythrocytes (PCE) to total erythrocytes.
      We conclude that fucoidan presents no significant genotoxic concern under the
      anticipated conditions of use.

PMID- 20138104
TI  - Effect of selenium enrichment on antioxidant activities and chemical composition
      of Lentinula edodes (Berk.) Pegl. mycelial extracts.
AB  - Preparations derived from Lentinula edodes (Berk.) Pegl. mycelium are worldwide
      used as dietary supplements containing compounds active as immune system
      enhancers, demonstrating chemopreventive and anticancer activity. L. edodes
      mycelium enriched with organic forms of selenium like selenized yeast possess
      putative, higher cancer preventive properties. The objective of this study was to
      test the effect of enrichment in selenium on antioxidant, reducing and free
      radical scavenging activity of water and alcohol extracts from mycelium of L.
      edodes (Berk.). To elucidate the cause of enhanced antioxidant activity of
      extracts, a preliminary selenium speciation by specific oxido-reduction reaction
      was performed. Se-enrichment enhanced antioxidant activity, reducing power and
      free radical scavenging effect of mycelial extracts by almost 100-400%. Increase
      of activity was particularly high for diluted extracts (concentrations 0.1-0.5
      mg/ml). The chemical composition of extracts from both Se-enriched and non
      enriched mycelium was compared by determination of polyphenols, proteins,
      carbohydrates and lipids. Results showed that Se-enrichment enhanced antioxidant
      activities of mycelial extracts, likely by high amounts of organic Se-compounds (
      II oxidation state) and elemental red selenium, and by increased polyphenols
      content. Our results suggest that Se-enrichment is a good method for enhancement
      of important activities of human dietary supplements, including Shiitake
      preparations.

PMID- 20138105
TI  - Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial
      cells but not in MCF7 and MDA-MB-231 human breast cancer cells.
AB  - Until now, very little has been known about the antioxidant capacity of squalene
      and its effect on human breast tumourigenesis. In the present work, we
      investigated squalene's scavenging properties and its effect on cell
      proliferation, cell cycle profile, apoptosis, reactive oxygen species (ROS) level
      and oxidative DNA damage, using human breast cell lines. Our results showed that
      squalene neither possesses scavenging activity nor significantly alters cell
      proliferation rates, the cell cycle profile or cell apoptosis in human mammary
      epithelial cells (MCF10A), minimally invasive (MDA-MB-231) breast cancer cells,
      and highly invasive (MCF7) breast cancer cells. However, we found that squalene
      did exert the following effects on MCF10A epithelial cells in a dose-dependent
      manner: (a) it decreased intracellular ROS level, (b) it prevented H(2)O(2)
      induced oxidative injury, and (c) it protected against oxidative DNA damage.
      Interestingly, squalene did not exert these effects on MCF7 and MDA-MB-231 cancer
      cells. Therefore, our data suggest that squalene, found in high amounts in virgin
      olive oils, could be partially responsible for the lower incidence of breast
      cancer in populations that consume the Mediterranean diet due to its protective
      activity against oxidative DNA damage in normal mammary cells.

PMID- 20138106
TI  - Equilibrium and kinetics of the unfolding and refolding of Escherichia coli
      Malate Synthase G monitored by circular dichroism and fluorescence spectroscopy.
AB  - The equilibrium and kinetics studies of an 82 kDa large monomeric Escherichia
      coli protein Malate Synthase G (MSG) was investigated by far and near-UV CD,
      intrinsic tryptophan fluorescence and extrinsic fluorescence spectroscopy. We
      find that despite of its large size, folding is reversible, in vitro. Equilibrium
      unfolding process of MSG exhibited three-state transition thus, indicating the
      presence of at least a stable equilibrium intermediate. Thermodynamic parameters
      suggest this intermediate resembles the unfolded state. However, the equilibrium
      intermediate exhibits pronounced secondary structure as measured by far-UV CD,
      partial tertiary structure as delineated by near-UV CD, compactness (m value) and
      exposed hydrophobic surface area as assessed by ANS binding, typically depicting
      a molten globule state. The stopped-flow kinetic data provide clear evidence for
      the presence of a burst phase during the refolding pathway due to the formation
      of an early Intermediate, within the dead time of the instrument. Refolding from
      4 M to various lower concentrations until 0.4 M of GdnHCl follow biphasic
      kinetics at lower concentrations of GdnHCl (<0.8 M), whereas monophasic kinetics
      at concentrations above 1.5 M. Also, rollover in the refolding and unfolding
      limbs of chevron plot verifies the presence of a fast kinetic intermediate at
      lower concentration of GdnHCl. Based upon the above observations we hereby
      propose the folding pathway of a large multi-domain protein Malate Synthase G.

PMID- 20138107
TI  - Compacting effect of BBR3464, a new-generation trisplatinum anticancer agent, on
      DNA.
AB  - BBR3464 is a trinuclear platinum compound of formula [{trans-PtCl(NH(3))(2)}(2)
      mu-trans-Pt(NH(3))(2){NH(2)(CH(2))(6)NH(2)}(2)](4+). It is a new-generation
      platinum chemotherapeutic agent that exhibits cytotoxicity at ten to thousand
      times lower dose limit compared to the well-known platinum drug cisplatin, in
      cisplatin-sensitive as well as in cisplatin-resistant cells. DNA is thought to be
      the primary cellular target of BBR3464. In this work, we have applied high
      resolution atomic force microscopy (AFM) for the first time, to obtain direct
      information on BBR3464-induced structural changes of DNA. It is found that the
      DNA molecules get compacted after treatment with BBR3464, for the drug:DNA molar
      ratio and the drug treatment period of 0.01 and 48 h, respectively. These values
      of molar ratio and incubation period have been obtained previously, as a result
      of biochemical optimization studies carried out for achieving maximum drug
      effects. The DNA structural changes, as observed in AFM topographs, have been
      correlated to the bulk level spectroscopic information. A remark on the
      significance of BBR3464-induced DNA compaction with respect to the available AFM
      reports on DNA modification by cisplatin has been made.

PMID- 20138108
TI  - 1-Cysteine peroxiredoxin: A dual-function enzyme with peroxidase and acidic Ca2+
      independent phospholipase A2 activities.
AB  - Peroxiredoxins (Prx) are enzymes that catalyze the reduction of hydrogen peroxide
      and alkyl hydroperoxides. Prxs are ubiquitous enzymes with representatives found
      in Bacteria, Archaea and Eukarya. Many 1-cysteine peroxiredoxins (1-CysPrx) are
      dual-function enzyme with both peroxidase and acidic Ca(2+)-independent
      phospholipase A(2) (aiPLA(2)) activities. The functions proposed for 1
      CysPrx/aiPLA(2) include the protection of cell membrane phospholipids against
      oxidative damage (peroxidation) and the metabolism (hydrolysis) of phospholipids,
      such as those of lung surfactant. The peroxidase active site motif PVCTTE of 1
      CysPrx contains the conserved catalytic cysteine residue, and the esterase
      (lipase) motif GXSXG of the enzyme contains the conserved catalytic serine
      residue. In addition to the classic lipase motif GXSXG, various 1
      CysPrx/aiPLA(2)s have closely related variant putative lipase motifs containing
      the catalytic serine residue. The PLA(2) moieties are prevalent and highly
      homologous in vertebrate and bacterial 1-CysPrx/aiPLA(2)s that is consistent with
      a high degree evolutional conservation of the enzyme.

PMID- 20138109
TI  - Structural requirement for PPARgamma binding revealed by a meta analysis of holo
      crystal structures.
AB  - PPARgamma is a ligand regulated transcriptional factor that modulates the
      transcription of several genes involved in fat and sugar metabolism. Due to its
      easy bacterial expression and crystallization, several crystal structures of holo
      PPARgamma have been reported and deposited in the Protein Data Bank. Here, we
      investigated the three-dimensional electrostatic properties of 55 PPARgamma
      ligands and used this information for clustering them through principal component
      analysis. We found out that, according to their electrostatic potential, these
      ligands can be separated in three groups, with different binding features. We
      also observed that non-selective and selective ligands show different 3D
      electrostatic properties and are separated in different clusters. The relevance
      of this analysis for the development of new binders is discussed.

PMID- 20138110
TI  - Covert cognition in the persistent vegetative state.
AB  - Brain damage can sometimes render a patient persistently unresponsive and yet
      apparently awake, admitting the possibility that the absence of overt voluntary
      behaviour might conceal a retained capacity for covert cognition. When given
      instructions to perform a cognitive task, a minority of patients in such a so
      called persistent vegetative state (PVS) has recently been found to exhibit
      patterns of brain activation closely matching those observed in normal subjects
      obeying the same instructions. These data have been widely interpreted as
      implying the detection of covert "consciousness". Here we show that this
      inference is not supported by the extant data because it relies on critical
      assumptions, obscured by conceptual unclarities, that are either untested or
      untestable. We set out the proper grounds for ascribing psychological attributes
      to PVS patients from physiological evidence of any kind, and offer a perspicuous
      conceptual framework for future empirical studies in the field.

PMID- 20138111
TI  - The diffuse chemosensory system: exploring the iceberg toward the definition of
      functional roles.
AB  - The diffuse chemosensory system (DCS) is an anatomical structure composed of
      solitary chemosensory cells (SCCs, also called solitary chemoreceptor cells),
      which have analogies with taste cells but are not aggregated in buds. The concept
      of DCS has been advanced, after the discovery that cells similar to gustatory
      elements are present in several organs. The elements forming the DCS share common
      morphological and biochemical characteristics with the taste cells located in
      taste buds of the oro-pharyngeal cavity but they are localized in internal
      organs. In particular, they may express molecules of the chemoreceptorial cascade
      (e.g. trans-membrane taste receptors, the G-protein alpha-gustducin, PLCbeta2,
      TRPM5). This article will focus on the mammalian DCS in apparatuses of endodermic
      origin (i.e. digestive and respiratory systems), which is composed of an enormous
      number of sensory elements and presents a multiplicity of morphological aspects.
      Recent research has provided an adequate description of these elements, but the
      functional role for the DCS in these apparatuses is unknown. The initial findings
      led to the definition of a DCS structured like an iceberg, with a mysterious
      "submerged" portion localized in the distal part of endodermic apparatuses.
      Recent work has focussed on the discovery of this submerged portion, which now
      appears less puzzling. However, the functional roles of the different cytotypes
      belonging to the DCS are not well known. Recent studies linked chemosensation of
      the intraluminal content to local control of absorptive and secretory (exocrine
      and endocrine) processes. Control of the microbial population and detection of
      irritants seem to be other possible functions of the DCS. In the light of these
      new findings, the DCS might be thought to be involved in a wide range of diseases
      of both the respiratory (e.g. asthma, chronic obstructive pulmonary disease,
      cystic fibrosis) and digestive apparatuses (absorptive or secretive diseases,
      dysmicrobism), as well as in systemic diseases (e.g. obesity, diabetes). A
      description of the functional roles of the DCS might be a first step toward the
      discovery of therapeutic approaches which target chemosensory mechanisms.

PMID- 20138112
TI  - Astrocytic beta(2)-adrenergic receptors: from physiology to pathology.
AB  - Evidence accumulates for a key role of the beta(2)-adrenergic receptors in the
      many homeostatic and neuroprotective functions of astrocytes, including glycogen
      metabolism, regulation of immune responses, release of neurotrophic factors, and
      the astrogliosis that occurs in response to neuronal injury. A dysregulation of
      the astrocytic beta(2)-adrenergic-pathway is suspected to contribute to the
      physiopathology of a number of prevalent and devastating neurological conditions
      such as multiple sclerosis, Alzheimer's disease, human immunodeficiency virus
      encephalitis, stroke and hepatic encephalopathy. In this review we focus on the
      physiological functions of astrocytic beta(2)-adrenergic receptors, and their
      possible impact in disease states.

PMID- 20138114
TI  - Hypoxia mediates low cell-cycle activity and increases the proportion of long
      term-reconstituting hematopoietic stem cells during in vitro culture.
AB  - OBJECTIVE: Recent evidence suggests that hematopoietic stem cells (HSCs) in the
      bone marrow (BM) are located in areas where the environment is hypoxic. Although
      previous studies have demonstrated positive effects by hypoxia, its role in HSC
      maintenance has not been fully elucidated, neither has the molecular mechanisms
      been delineated. Here, we have investigated the consequence of in vitro
      incubation of HSCs in hypoxia prior to transplantation and analyzed the role of
      hypoxia-inducible factor (HIF)-1alpha. MATERIALS AND METHODS: HSC and progenitor
      populations isolated from mouse BM were cultured in 20% or 1% O(2), and analyzed
      for effects on cell cycle, expression of cyclin-dependent kinase inhibitors
      genes, and reconstituting ability to lethally irradiated mice. The involvement of
      HIF-1alpha was studied using methods of protein stabilization and gene silencing.
      RESULTS: When long-term FLT3(-)CD34(-) Lin(-)Sca-1(+)c-Kit(+) (LSK) cells were
      cultured in hypoxia, cell numbers were significantly reduced in comparison to
      normoxia. This was due to a decrease in proliferation and more cells accumulating
      in G(0). Moreover, the proportion of HSCs with long-term engraftment potential
      was increased. Whereas expression of the cyclin-dependent kinase inhibitor genes
      p21(cip1), p27(Kip1), and p57(Kip2) increased in LSK cells by hypoxia, only
      p21(cip1) was upregulated in FLT3(-)CD34(-)LSK cells. We could demonstrate that
      expression of p27(Kip1) and p57(Kip2) was dependent of HIF-1alpha. Surprisingly,
      overexpression of constitutively active HIF-1alpha or treatment with the HIF
      stabilizer agent FG-4497 led to a reduction in HSC reconstituting ability.
      CONCLUSIONS: Our results imply that hypoxia, in part via HIF-1alpha, maintains
      HSCs by decreasing proliferation and favoring quiescence.

PMID- 20138115
TI  - Pig preovulatory oocytes modulate cumulus cell protein and gene expression in
      vitro.
AB  - This study investigated the changes in protein and gene expression in
      oocytectomized cumulus cells (OOX) of medium-sized follicles from gilts, cultured
      with or without denuded oocytes isolated from large oestrogenic sow follicles.
      Proteomic analysis identified 14 proteins that were differentially expressed in
      OOX, of which the protein 14-3-3 eta, a signal transduction pathway modulator,
      was down-regulated in the presence of oocytes. Oocyte co-culture also down
      regulated FSHR mRNA expression in OOX, as measured by real-time PCR, and FSHR and
      14-3-3 eta mRNA abundance were positively correlated. The oocyte also up
      regulated HSD3B mRNA, suggesting an effect on cumulus cell progesterone
      synthesis. Together with data on gene expression in granulosa cells during the
      follicular phase of the sow oestrous cycle, this study suggests that modulation
      of the expression of steroidogenesis related proteins and genes in cumulus cells
      by the porcine preovulatory oocyte reflects the specific physiological
      requirements of the preovulatory follicle.

PMID- 20138113
TI  - Histories of major depression and premenstrual dysphoric disorder: Evidence for
      phenotypic differences.
AB  - This study examined unique versus shared stress and pain-related phenotypes
      associated with premenstrual dysphoric disorder (PMDD) and prior major depressive
      disorder (MDD). Sympathetic nervous system (SNS) and hypothalamic-pituitary
      adrenal (HPA)-axis measures were assessed at rest and during mental stress, as
      well as sensitivity to cold pressor and tourniquet ischemic pain tasks in four
      groups of women: (1) non-PMDD with no prior MDD (N=18); (2) non-PMDD with prior
      MDD (N=9); (3) PMDD with no prior MDD (N=17); (4) PMDD with prior MDD (N=10).
      PMDD women showed blunted SNS responses to stress compared to non-PMDD women,
      irrespective of prior MDD; while women with prior MDD showed exaggerated
      diastolic blood pressure responses to stress versus never depressed women,
      irrespective of PMDD. However, only in women with histories of MDD did PMDD women
      have lower cortisol concentrations than non-PMDD women, and only in non-PMDD
      women was MDD associated with reduced cold pressor pain sensitivity. These
      results suggest both unique phenotypic differences between women with PMDD and
      those with a history of MDD, but also indicate that histories of MDD may have
      special relevance for PMDD.

PMID- 20138116
TI  - Molecular prognostic markers in papillary and follicular thyroid cancer: Current
      status and future directions.
AB  - Gene expression profiling shows that, by gene signature, the difference between
      BRAF-positive and BRAF-negative PTC is so distinct that BRAF-positive cancer may
      be regarded as a molecular subtype of papillary thyroid cancer (PTC). Since much
      enthusiasm surrounds the BRAF-oncogene as a molecular prognostic factor, a
      central focus of our consideration is to weigh the current arguments for and
      against applying BRAF mutation status of the tumor in clinical practice. The
      frequency of BRAF mutation in PTC is high-45% on average, with values over 70-80%
      in some populations. This will mean that implementing BRAF mutation as a factor
      of poor prognosis will shift many PTC patients, considered up to now as low risk
      ones, to the more extensive treatment. We estimate that 31% of all PTC patients
      and 39% of those diagnosed with stage I-II disease will face the risk of
      overtreatment if the decision will be based on the BRAF-positivity of their
      tumors. Also, the risk of undertreatment in the young patients with BRAF-negative
      tumors is evaluated with 26%. We think that, as of now, the evidence-based
      support for such consequences is still weak. Thus, there is urgent need to look
      for genes or gene signatures which will be helpful in the stratification of BRAF
      positive tumors to specify these with poor prognosis with higher accuracy, needed
      for clinical decisions. Considering this, in the review we summarize the present
      status of knowledge on other prognosis-related gene expression changes in
      papillary and follicular cancer and relate them to he tumor's biology.

PMID- 20138117
TI  - Insulin and NPY pathways and the control of GnRH function and puberty onset.
AB  - Energy balance exerts a critical influence on reproductive function. Leptin and
      insulin are among the metabolic factors signaling the nutritional status of an
      individual to the hypothalamus, and their role in the overall modulation of the
      activity of GnRH neurons is increasingly recognized. As such, they participate to
      a more generalized phenomenon: the signaling of peripheral metabolic changes to
      the central nervous system. The physiological importance that the interactions
      occurring between peripheral metabolic factors and the central nervous system
      bear for the control of food intake is increasingly recognized. The central
      mechanisms implicated are the focus of attention of very many research groups
      worldwide. We review here the experimental data that suggest that similar
      mechanisms are at play for the metabolic control of the neuroendocrine
      reproductive function. It is appearing that metabolic signals are integrated at
      the levels of first-order neurons equipped with the proper receptors, ant that
      these neurons send their signals towards hypothalamic GnRH neurons which
      constitute the integrative element of this network.

PMID- 20138118
TI  - A coded VEP method to measure interhemispheric transfer time (IHTT).
AB  - Interhemispheric transfer time (IHTT) is an important parameter for research on
      the information conduction time across the corpus callosum between the two
      hemispheres. There are several traditional methods used to estimate the IHTT,
      including the reaction time (RT) method, the evoked potential (EP) method and the
      measure based on the transcranial magnetic stimulation (TMS). The present study
      proposes a novel coded VEP method to estimate the IHTT based on the specific
      properties of the m-sequence. These properties include good signal-to-noise ratio
      (SNR) and high noise tolerance. Additionally, calculation of the circular cross
      correlation function is sensitive to the phase difference. The method presented
      in this paper estimates the IHTT using the m-sequence to encode the visual
      stimulus and also compares the results with the traditional flash VEP method.
      Furthermore, with the phase difference of the two responses calculated using the
      circular cross-correlation technique, the coded VEP method could obtain IHTT
      results, which does not require the selection of the utilized component.

PMID- 20138119
TI  - Embryonic exposure to ethanol disturbs regulation of mitotic spindle orientation
      via GABA(A) receptors in neural progenitors in ventricular zone of developing
      neocortex.
AB  - Neural progenitors in the ventricular zone of the developing neocortex divide
      oriented either parallel or perpendicular to the ventricular surface based on
      their mitotic spindle orientation. It has been shown that the cleavage plane
      orientation is developmentally regulated and plays a crucial role in cell fate
      determination of neural progenitors or the maintenance of the proliferative
      ventricular zone during neocortical development. We tested if fetal exposure to
      ethanol, the most widely used psychoactive agent and a potent teratogen that may
      cause malformation in the central nervous system, alters mitotic cleavage
      orientation of the neural progenitors at the apical surface of the ventricular
      zone in the developing neocortex. Fetal exposure to ethanol on E10.5 and 11.5
      increased the occurrence frequency of a horizontal cleavage plane that is
      parallel to the ventricular surface on E 12.5. Administration of picrotoxin, a
      GABA(A) receptor antagonist, prior to ethanol administration canceled the effect
      of ethanol with the frequency of horizontal division similar to the control
      level, although picrotoxin itself did not show any effect on cleavage plane
      orientation. Phenobarbital, a GABA(A) receptor agonist, induced horizontal
      cleavage to an extent similar to that induced by ethanol administration.
      (+)MK801, an antagonist of NMDA receptor that is another major target of ethanol
      in neural cells, did not affect the cleavage plane of dividing progenitors. These
      results suggest that fetal ethanol exposure induced alterations in the cleavage
      plane orientation of neural progenitors in the ventricular zone of the neocortex
      via the enhancement of the function of GABA(A) receptors.

PMID- 20138120
TI  - Prosody-syntax interactions in aging: event-related potentials reveal
      dissociations between on-line and off-line measures.
AB  - This study used ERPs to determine whether older adults use prosody in resolving
      early and late closure ambiguities comparably to young adults. Participants made
      off-line acceptability judgments on well-formed sentences or those containing
      prosody-syntax mismatches. Behaviorally, both groups identified mismatches, but
      older subjects accepted mismatches significantly more often than younger
      participants. ERP results demonstrate CPS components and garden-path effects
      (P600s) in both groups, however, older adults displayed no N400 and more anterior
      P600 components. The data provide the first electrophysiological evidence
      suggesting that older adults process and integrate prosodic information in real
      time, despite off-line behavioral differences. Age-related differences in
      neurocognitive processing mechanisms likely contribute to this dissociation.

PMID- 20138121
TI  - Na(x)-deficient mice show normal vasopressin response to dehydration.
AB  - In dehydrated animals, the antidiuretic hormone vasopressin (VP) is released from
      the nerve terminals of magnocellular neurons of the supraoptic nucleus (SON) and
      paraventricular nucleus (PVN) into the systemic circulation at the posterior
      pituitary. Increases in sodium (Na+)-level and osmolality in body fluids upon
      dehydration are reportedly sensed by a Na+-sensor and/or an osmosensor,
      respectively. However, it is still unknown whether both are involved in the
      regulation of production and/or release of VP. Na(x) is the cerebral Na+-level
      sensor and Na(x)-knockout mice do not stop ingesting salt even when dehydrated.
      Here we examined VP production/release in Na(x)-knockout mice, and found that
      they are normal in the VP response to dehydration or intraperitoneal
      administration with hypertonic saline. In situ hybridization using an intron
      specific probe showed that VP gene expression in the SON did not differ from wild
      type mice when dehydrated. Also, there was no significant difference in the
      activity of subfornical organ neurons projecting to the SON between the two
      genotypes when stimulated by water deprivation. Furthermore, Na(x)-knockout mice
      showed a normal response in urine excretion to dehydration. All these results
      indicate that the information of Na+-level increase detected by Na(x) does not
      contribute to the control of VP production/release.

PMID- 20138122
TI  - P-glycoprotein expression and function are increased in an animal model of
      amyotrophic lateral sclerosis.
AB  - The efflux pumps located at the blood-brain barrier (BBB) prevent drugs entering
      the brain. As such, efflux pumps are a major obstacle to drug brain distribution.
      Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with
      little therapeutics available: riluzole is the only drug approved in its
      treatment. The lack of response to treatment in ALS may be, at least in part, due
      to increased activities of efflux pumps in relation to disease, leading to
      subtherapeutic brain concentrations of drugs. In the present study, we used a
      transgenic mouse model of ALS (G86R mSOD1 mice) to test this hypothesis.
      Expression and functionality of P-glycoprotein (ABCB1, P-gp) and Breast Cancer
      Resistance Protein (ABCG2, BCRP), two major efflux pumps, were studied. We
      observed an increased P-gp expression (1.5-fold) in presymptomatic mSOD1 mice
      compared to wild-type controls. Consistent with this, P-gp function was also
      increased by 1.5-fold and riluzole brain disposition was decreased by 1.7-fold in
      mSOD1 mice. Contrasting with this, BCRP expression and function were unaltered by
      the pathology. These results demonstrate that BBB transport proteins are modified
      in G86R mSOD1 mice ALS model. Such findings underline potential problems in
      extrapolating the results of animal studies to humans and developing clinical
      trials, especially for drugs transported by P-gp.

PMID- 20138123
TI  - Effects of ipsilateral cerebellum ablation on acquisition and retention of
      classically conditioned eyeblink responses in rats.
AB  - The ipsilateral cerebellum to the trained eye has been reported to be essential
      for acquisition and retention of the conditioned response (CR) in rabbit eyeblink
      conditioning. Although pharmacological studies have suggested its important roles
      in other species too, to what degree does eyeblink conditioning in rats depend on
      the ipsilateral cerebellum is not clear. In this work, we ablated the ipsilateral
      cerebellum in rats before or after conditioning to examine its roles in
      acquisition and retention of the CR. In the first experiment, rats received
      ablation of the ipsilateral cerebellum and recovered for more than 3 weeks. They
      then underwent eyeblink conditioning for 7 days with a tone and a periorbital
      electrical shock. Consistent with other previous reports, hemicerebellectomized
      rats showed significant impairment compared to sham-lesioned rats. However, the
      hemicerebellectomized rats acquired CRs to some degree, and the acquired CR
      showed adaptive timing. In the second experiment, rats received the
      hemicerebellectomy after acquiring CR by 7 days of conditioning in a delay
      paradigm. After more than 3 weeks of recovery, they were again conditioned in a
      delay paradigm. Rats with ipsilateral cerebellar lesions showed severe impairment
      in retention of the pre-acquired CR; however, they reacquired CR to some degree
      during the subsequent reconditioning sessions. These results suggest that the
      ipsilateral cerebellum plays an important role in rat eyeblink conditioning as
      well but that other brain regions can partially compensate for its removal.

PMID- 20138124
TI  - -1154G/A and -2578C/A polymorphisms of the vascular endothelial growth factor
      gene in Tunisian Alzheimer patients in relation to beta-amyloid (1-42) and total
      tau protein.
AB  - Recent evidences indicate that polymorphisms within the promoter region of the
      vascular endothelial growth factor (VEGF) gene may elevate the risk for
      Alzheimer's disease (AD). To further investigate, we have analyzed association
      between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex
      matched 113 controls from Tunisian population. The distribution of genotype and
      allele frequencies of the VEGF (-2578C/A) and (-1154G/A) polymorphisms did not
      differ significantly between AD and control groups (p>0.05). In the subgroup of
      ApoE varepsilon4 carriers, the -2578A was observed to be significantly higher in
      the AD patients than in the control individuals. After adjusting the data by
      gender, age and the ApoE varepsilon4 status using logistic regression, the -2578A
      allele was found to increase the risk for sporadic AD by 1.7-fold. The present
      study provides the evidence that the -2578A allele may be associated with the
      development of AD in the individuals with ApoE varepsilon4 allele. In addition,
      AD patients carrying the -2578A allele had lower Abeta42 (p=0.029) levels than
      those without this allele, particularly in subjects with ApoE varepsilon4 allele.

PMID- 20138125
TI  - Calcitonin gene-related peptide differentially regulates gene and protein
      expression in trigeminal glia cells: findings from array analysis.
AB  - Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide
      implicated in inflammatory diseases involving trigeminal ganglion nerve
      activation. Within trigeminal ganglia, satellite glia and Schwann cells are found
      in close association with neuronal cell bodies and fibers, respectively, and are
      known to express functional CGRP receptors. The goal of this study was to use
      array analysis to provide a more comprehensive understanding of CGRP regulation
      of inflammatory proteins and genes in trigeminal glia. Primary trigeminal ganglia
      cultures enriched for glia were treated with 500 nM CGRP for 8 or 24h. CGRP
      caused a >3-fold increase in the level of 19 cytokines 8h after CGRP treatment
      and the levels of each of these cytokines remained significantly elevated over
      basal unstimulated levels at 24h. While mRNA levels of many genes involved in
      mitogen-activated protein (MAP) kinase signaling were increased 8h after CGRP
      treatment, the number of responsive genes was greatly increased at 24h.
      Specifically, CGRP was shown to temporally regulate expression of multiple MAP
      kinases as well as numerous MAP kinase-responsive genes including transcription
      factors, scaffold/anchoring proteins, and cell cycle proteins. Thus, our data
      provide evidence of an emerging role of CGRP as an important modulator of
      trigeminal ganglion glia by stimulating cytokine release as well as inducing
      expression of a diverse array of proteins involved in MAP kinase signaling.

PMID- 20138126
TI  - The multifaceted capacity of Dps proteins to combat bacterial stress conditions:
      Detoxification of iron and hydrogen peroxide and DNA binding.
AB  - BACKGROUND: The widely expressed Dps proteins, so named after the DNA-binding
      properties of the first characterized member of the family in Escherichia coli,
      are considered major players in the bacterial response to stress. SCOPE OF
      REVIEW: The review describes the distinctive features of the "ferritin-like"
      ferroxidation reaction, which uses hydrogen peroxide as physiological iron
      oxidant and therefore permits the concomitant removal of the two reactants that
      give rise to hydroxyl radicals via Fenton chemistry. It also illustrates the
      structural elements identified to date that render the interaction of some Dps
      proteins with DNA possible and outlines briefly the significance of Dps-DNA
      complex formation and of the Dps interaction with other DNA-binding proteins in
      relation to the organization of the nucleoid and microbial survival. GENERAL
      SIGNIFICANCE: Understanding in molecular terms the distinctive role of Dps
      proteins in bacterial resistance to general and specific stress conditions. MAJOR
      CONCLUSIONS: The state of the art is that the response to oxidative and peroxide
      mediated stress is mediated directly by Dps proteins via their ferritin-like
      activity. In contrast, the response to other stress conditions derives from the
      concerted interplay of diverse interactions that Dps proteins may establish with
      DNA and with other DNA-binding proteins.

PMID- 20138127
TI  - Hippocampal increased cell death and decreased cell density elicited by nicotine
      and/or ethanol during adolescence are reversed during drug withdrawal.
AB  - We have recently identified hippocampal cell death and reduced neuronal and glial
      cells densities during adolescent nicotine and ethanol exposures and outcomes
      reduced in severity when nicotine and ethanol are co-administered during this
      developmental period. In the present study, we investigated the effects of
      adolescent nicotine and/or ethanol withdrawal on the following regions of the
      hippocampus: Granular layer of the Dentate Gyrus (GrDG), Molecular layer (Mol),
      CA1, CA2 and CA3. From the 30th to the 45th postnatal day (PN30-PN45), C57BL/6
      male and female mice were exposed to nicotine free base (NIC) and/or ethanol
      (ETOH). Four groups were analyzed: (1) concomitant NIC (50 microg/ml in 2%
      saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day)
      exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We evaluated cell
      degeneration (TUNEL assay), neuronal and glial densities (optical Disector) and
      region thicknesses two (PN47) and five (PN50) days post-exposure. On PN47, there
      were increases in the number of TUNEL+ cells in most hippocampal regions of both
      ETOH and NIC groups. In the NIC+ETOH group there were less severe effects. These
      results were paralleled by reductions in neuronal and glial cells densities for
      all treatment groups. In contrast, on PN50, ethanol and/or nicotine withdrawal
      were associated with compensatory reductions in TUNEL+ cells in all hippocampal
      regions. These results were paralleled by a reversal of effects on neuronal and
      glial densities so that there were no longer differences between groups. There
      were no effects on region thicknesses. These results suggest that deleterious
      effects of nicotine and/or ethanol are reversed during prolonged withdrawal.

PMID- 20138128
TI  - Loss of synaptotagmin IV results in a reduction in synaptic vesicles and a
      distortion of the Golgi structure in cultured hippocampal neurons.
AB  - Fusion of synaptic vesicles with the plasma membrane is mediated by the SNARE
      (soluble NSF attachment receptor) proteins and is regulated by synaptotagmin
      (syt). There are at least 17 syt isoforms that have the potential to act as
      modulators of membrane fusion events. Synaptotagmin IV (syt IV) is particularly
      interesting; it is an immediate early gene that is regulated by seizures and
      certain classes of drugs, and, in humans, syt IV maps to a region of chromosome
      18 associated with schizophrenia and bipolar disease. Syt IV has recently been
      found to localize to dense core vesicles in hippocampal neurons, where it
      regulates neurotrophin release. Here we have examined the ultrastructure of
      cultured hippocampal neurons from wild-type and syt IV -/- mice using electron
      tomography. Perhaps surprisingly, we observed a potential synaptic vesicle
      transport defect in syt IV -/- neurons, with the accumulation of large numbers of
      small clear vesicles (putative axonal transport vesicles) near the trans-Golgi
      network. We also found an interaction between syt IV and KIF1A, a kinesin known
      to be involved in vesicle trafficking to the synapse. Finally, we found that syt
      IV -/- synapses exhibited reduced numbers of synaptic vesicles and a twofold
      reduction in the proportion of docked vesicles compared to wild-type. The
      proportion of docked vesicles in syt IV -/- boutons was further reduced, 5-fold,
      following depolarization.

PMID- 20138129
TI  - Analysis of Mount Atlas mastic smoke: a potential food preservative.
AB  - Pistacia terebinthus L. smoke has been used traditionally in Iran as disinfectant
      and air purifier. Smoke was collected by a simple method, and the chemical
      constituents and antimicrobial activity of the smoke were analyzed. The chemical
      constituents of the smoke were alpha-pinene (65.1%), limonene (11.5%) and allo
      ocimene (2.8%). The non polar phase of smoke noticeably inhibited the growth of
      different microorganisms. MIC test shows that non polar fraction of smoke can
      inhibit the growth of some bacteria. The results indicating that the properties
      of the smoke as a flavoring and preservative agent could be a potential subject
      for future studies.

PMID- 20138130
TI  - Effect of divalent anions on photodegradation kinetics and pathways of riboflavin
      in aqueous solution.
AB  - The present investigation is based on a study of the effect of buffer and non
      buffer divalent anions (phosphate, sulphate, tartrate, succinate, malonate) on
      the kinetics, product distribution and photodegradation pathways of riboflavin
      (RF) at pH 6.0-8.0. RF solutions (5x10(-5)M) were photodegraded in the presence
      of divalent anions (0.2-1.0M) using a visible light source and the photoproducts,
      cyclodehydroriboflavin (CDRF), formylmethylflavin (FMF), lumichrome (LC) and
      lumiflavin (LF) were assayed by a specific multicomponent spectrophotometric
      method. RF degradation in the presence of divalent anions follows parallel first
      order kinetics to give CDRF and LC as the final products through photoaddition
      and photoreduction reactions, respectively. The divalent anion-catalysed CDRF
      formation is affected in the order:
      phosphate>sulphate>tartrate>succinate>malonate, showing maximum activity of the
      anions around pH 7. The divalent anions cause deviation of the photoreduction
      pathway in favour of the photoaddition pathway to form CDRF. The first- and
      second-order rate constants for the reactions involved in the photodegradation of
      RF have been determined and the rate-pH profiles and pathway relationships
      discussed. The catalytic activity of the divalent anions appears to be a function
      of the relative strength and chemical reactivity of the RF-divalent anion complex
      acting as a mediator in the photoaddition reaction.

PMID- 20138131
TI  - Solventless visible light-curable coating: I. Critical formulation and processing
      parameters.
AB  - Film coating is generally accomplished by spraying polymers dissolved in solvents
      onto a cascading bed of tablets. The limitations associated with the use of
      solvents (both aqueous and organic) can be overcome by the use of solventless
      coating technologies. In this proposed solventless photocurable film coating
      system, each layer of coating onto the pellets (non-pareil beads) was formed
      using liquid photocurable monomer, powdered pore-forming agents, photosensitizers
      and photoinitiators in a mini-coating pan and later cured by visible light.
      Yield, coating efficiency, variation in color, diameter and roundness were
      determined for each batch to evaluate process efficiency and coating quality. It
      was found that the ratio (S/L ratio) of the amount of solid (S) pore-forming
      agent to volume of liquid (L) monomer, particle size and type of the pore-forming
      agent, concentration of initiator, and total exposure (light intensity x exposure
      time) of light were critical formulation and processing parameters for the
      process. Using lactose as a pore-forming agent, an optimum ratio of pore-forming
      agent to photocurable polymer was 1.8-3.0 to achieve good process efficiency and
      uniformity. The ratio was sensitive to particle size and type of pore-forming
      agent.

PMID- 20138132
TI  - Effects of SYJN, a Chinese herbal formula, on chronic unpredictable stress
      induced changes in behavior and brain BDNF in rats.
AB  - AIM OF THE STUDY: Suyu-Jiaonang (SYJN) is a Chinese herbal formula that contains
      four herbs: Bupleurum chinense DC, Curcuma aromatica Salisb., Perilla frutescens
      (Linn.) Britt., and Acorus tatarinowii Schott. Previous studies conducted in our
      laboratory have revealed an antidepressant-like effect of the formula in various
      mouse models of behavioral despair. The present study aimed to investigate
      whether SYJN could produce antidepressant-like effects in chronic unpredictable
      stress (CUS)-induced depression model in rats and its possible mechanism(s).
      MATERIALS AND METHODS: Rats were subjected to an experimental setting of CUS. The
      effect of SYJN treatment on CUS-induced depression was examined using behavioral
      tests including the sucrose consumption and open field tests. The mechanism
      underlying the antidepressant-like action of SYJN was examined by measuring brain
      derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues
      of CUS-exposed rats. RESULTS: Exposure to CUS for 4 weeks caused depression-like
      behavior in rats, as indicated by significant decreases in sucrose consumption
      and locomotor activity (assessed in the open field test). In addition, it was
      found that BDNF protein and mRNA levels in the hippocampus and frontal cortex
      were lower in CUS-treated rats, as compared to controls. Daily intragastric
      administration of SYJN (1300 or 2600 mg/kg) during the 4-week period of CUS
      significantly suppressed behavioral changes and attenuated the CUS-induced
      decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex.
      CONCLUSION: The results suggest that SYJN alleviates depression induced by CUS.
      The antidepressant-like activity of SYJN is likely mediated by the increase in
      BDNF expression in brain tissues.

PMID- 20138133
TI  - Cordyceps pruinosa extracts induce apoptosis of HeLa cells by a caspase dependent
      pathway.
AB  - AIM OF THE STUDY: Cordyceps is a parasitic fungus and has long been used as a
      traditional Chinese medicine to treat illnesses, promote longevity, increase
      athletic power, and relieve exhaustion and cancer. In this study, we reveal the
      mechanisms underlying apoptosis induced by Cordyceps pruinosa butanol fraction
      (CPBF) in the human cervical adenocarcinoma cell line, HeLa. MATERIALS AND
      METHODS: Proliferation and apoptosis of cells were examined by MTT assay, DNA
      fragmentation, phosphatidyl serine distribution assay, Western blot analysis, and
      immunocytochemistry. To determine the association between CPBF related apoptosis
      and ROS, electron spin resonance (ESR) trapping experiments were used. RESULTS:
      CPBF inhibited proliferation and induced apoptosis in HeLa cells in a dose
      dependent manner using a MTT assay, DNA fragmentation, and a phosphatidyl serine
      distribution assay. Western blot analysis showed that apoptosis in HeLa cells was
      caspase-3- and -9-dependent. Proteolytic cleavage of PARP and the release of
      cytochrome c from the mitochondria into the cytosol were significantly increased
      and the Bcl-2/Bax protein ratio was decreased. Apoptosis induced by CPBF was not
      prevented by various antioxidants. CONCLUSIONS: These results indicate that
      apoptotic effects of CPBF on HeLa cells are mediated by mitochondria-dependent
      death-signaling pathway independent of reactive oxygen species, suggesting that
      CPBF might be effective as an anti-proliferative agent for cancer.

PMID- 20138134
TI  - In vitro biological activities of niloticane, a new bioactive cassane diterpene
      from the bark of Acacia nilotica subsp. kraussiana.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Acacia nilotica subsp. kraussiana was reported in
      African traditional medicine for the treatment of various ailments. Isolation of
      an active compound in this study from the bark extract may lead to the validation
      of its efficiency as a traditional crude drug. AIMS OF THE STUDY: This study
      aimed to isolate active compound(s) from an ethyl acetate bark extract of Acacia
      nilotica subsp. kraussiana and to investigate some of its biological activity.
      MATERIALS AND METHODS: The isolation process was carried out using bioassay
      guided fractionation. The isolated compound was tested for antibacterial activity
      using the micro-dilution assay; anti-inflammatory activity using the COX-1 and
      COX-2 assays and investigated for inhibitory effect against acetylcholinesterase
      using the microplate assay. RESULTS: A new bioactive compound was isolated and
      identified as a cassane diterpene, niloticane. Niloticane showed antibacterial
      activity against Gram-positive bacteria Bacillus subtilis and Staphylococcus
      aureus with MIC values of 4 and 8microg/mL, respectively. With Gram-negative
      bacteria, niloticane showed weak activity. MIC values obtained were 16 and
      33microg/mL against Klebsiella pneumonia and Escherichia coli, respectively. In
      the cyclooxygenase test, niloticane possessed activity with IC50 values of 28 and
      210microM against COX-1 and COX-2, respectively. IC50 values observed with
      indomethacin (positive control) were 3.6microM for COX-1 and 189microM for COX-2.
      In the acetylcholinesterase test, niloticane showed anti-cholinesterase activity
      with an IC50 value of 4microM. IC50 values obtained by the galanthamine (positive
      control) was 2.0microM. CONCLUSION: The results obtained support the traditional
      uses of the bark of Acacia nilotica subsp. kraussiana in African traditional
      medicine for the treatment of some ailments that relate to microbial diseases,
      inflammation and central nervous system disorders.

PMID- 20138135
TI  - Acute diuretic activity of aqueous Erica multiflora flowers and Cynodon dactylon
      rhizomes extracts in rats.
AB  - AIM OF THE STUDY: The aim of the present study is to evaluate the diuretic
      potential and effect on urinary electrolytes of aqueous Erica multiflora L.
      (Ericaceae) flowers and Cynodon dactylon L. (Poaceae) rhizomes extracts in rats.
      MATERIALS AND METHODS: Different concentrations of these plants extract (0.125,
      0.250, and 0.500 g/kg of body weight) or the reference drug furosemide (0.015
      g/kg) were administrated orally to hydrated male Wistar rats and their urine
      output was measured at several interval of time after a single dose
      administration. Furthermore, a toxicological effect of both plants was undertaken
      as well. RESULTS: The results showed that furosemide induced significant diuresis
      and electrolytes excretion during the first hours. Plant extracts increased
      significantly urinary output and electrolytes excretion at the dose of 0.250 g/kg
      for Erica multiflora and 0.500 g/kg for Cynodon dactylon. This diuretic effect
      seems to be not related to K(+) plant content. Urinary pH remained mostly
      unchanged during the course of the study for both plant extracts. No lethality
      was observed among animals when using Erica multiflora even at the dose of 10
      g/kg while Cynodon dactylon, instead, caused 50% of rat death (LD50) at 4.5 g/kg.
      CONCLUSION: We concluded that both aqueous herb extracts administered,
      particularly, at the dose of 0.500 g/kg induce significant effect on urinary
      output of water and electrolytes and justify their use as diuretic remedy in
      traditional medicine.

PMID- 20138136
TI  - Anticonvulsant activity of DNS II fraction in the acute seizure models.
AB  - AIM OF THE STUDY: Delphinium nordhagenii belongs to family Ranunculaceae, it is
      widely found in tropical areas of Pakistan. Other species of Delphinium are
      reported as anticonvulsant and are traditionally used in the treatment of
      epilepsy. Delphinium nordhagenii is used by local healer in Pakistan but never
      used for scientific investigation as anticonvulsant. Thus, Delphinium nordhagenii
      was subjected to bioassay-guided fractionation and the most active fraction, i.e.
      DNS II acetone was chosen for further testing in the acute seizure models of
      epilepsy to study the antiepileptic potential in male mice. MATERIALS AND
      METHODS: Different doses (60, 65 and 70mg/kg, i.p.) of DNS II acetone fraction of
      Delphinium nordhagenii was administered 30min prior the chemoconvulsant's
      injection in the male mice. Convulsive doses of chemoconvulsants
      (pentylenetetrazole 90mg/kg, s.c. and picrotoxin 3.15mg/kg, s.c.) were used. The
      mice were observed 45-90min for the presence of seizures. Moreover, four
      different doses of DNS II (60, 65, 70 and 100mg/kg, i.p.) were tested in the MES
      test. RESULTS: The DNS II acetone fraction of Delphinium nordhagenii has
      exhibited the anticonvulsant actions by preventing the seizures against PTZ- and
      picrotoxin-induced seizure as well as 100% seizure protection in MES test. The
      results are comparable with standard AEDs (diazepam 7.5mg/kg, i.p. and phenytoin
      20mg/kg, i.p.). CONCLUSIONS: These findings suggest that the Delphinium
      nordhagenii possesses the anticonvulsant activity. Further analysis is needed to
      confirm the structure and target the extended activity profile.

PMID- 20138137
TI  - Melatonin and the time window for the expression of the alpha8 nicotinic
      acetylcholine receptor in the membrane of chick retinal cells in culture.
AB  - We have previously shown that melatonin influences the development of alpha8
      nicotinic acetylcholine receptor (nAChR) by measurement of the acetylcholine
      induced increase in the extracellular acidification rate (ECAR) in chick retinal
      cell cultures. Cellular differentiation that takes place between DIV (days in
      vitro) 4 and DIV 5 yields cells expressing alpha8 nAChR and results in a
      significant increase in the ECAR acetylcholine-induced. Blocking melatonin
      receptors with luzindole for 48h suppresses the development of functional alpha8
      nAChR. Here we investigated the time window for the effect of melatonin on
      retinal cell development in culture, and whether this effect was dependent on an
      increase in the expression of alpha8 nAChR. First, we confirmed that luzindole
      was inhibiting the effects of endogenous melatonin, since it increases 2-[(125)I]
      iodomelatonin (23pM) binding sites density in a time-dependent manner. Then we
      observed that acute (15, 60min, or 12h) luzindole treatment did not impair
      acetylcholine-induced increase in the ECAR mediated by activation of alpha8 nAChR
      at DIV 5, while chronic treatment (from DIV 3 or DIV 4 till DIV 5, or DIV 3.5
      till DIV 4.5) led to a time-dependent reduction of the increase in the
      acetylcholine-induced ECAR. The binding parameters for [(125)I]-alpha
      bungarotoxin (10nM) sites in membrane were unaffected by melatonin suppression
      that started at DIV 3. Thus, melatonin surges in the time window that occurs at
      the final stages of chick retinal cell differentiation in culture is essential
      for development of the cells expressing alpha8 nAChR subtype in full functional
      form.

PMID- 20138138
TI  - Effect of quaternary benzo[c]phenanthridine alkaloids sanguilutine and
      chelilutine on normal and cancer cells.
AB  - Sanguilutine and chelilutine, quaternary benzo[c]phenanthridine alkaloids, were
      studied for their antiproliferative activities with regard to their ability to
      induce oxidative stress. We observed potent antiproliferative activities for both
      alkaloids against three tumour (HeLa; HL-60; A-2780) and two normal (V-79; LEP)
      cell lines. Both alkaloids were efficient inductors of apoptosis. Statistical
      analysis revealed higher toxicity for sanguilutine compared to chelilutine and
      unequal sensitivity with regard to individual cell lines, although independent of
      the character of the cell line (i.e. tumour vs. normal). Dihydrofluorescein
      diacetate staining was used to measure intracellular ROS accumulation after
      treatment with sanguilutine, chelilutine, sanguinarine, and chelerythrine. In
      addition, anti-oxidative effects were studied. The effects of the alkaloids were
      compared with the effects of commonly used anti-oxidants, such as trolox,
      caffeine acid, and chlorogenic acid. None of the tested alkaloids (0.1 and 1
      microg/ml) increased ROS production. Pre-incubation of sanguinarine and
      chelilutine (at all tested concentrations) and sanguilutine and chelerythrine (1
      microg/ml) decreased oxidative stress caused by H(2)O(2). These findings indicate
      high antiproliferative and pro-apoptotic effects of sanguilutine and chelilutine
      that are not accompanied by oxidative stress induction, to the contrary, both
      alkaloids showed anti-oxidative effects.

PMID- 20138139
TI  - Sickness behaviour is induced by a peripheral CXC-chemokine also expressed in
      multiple sclerosis and EAE.
AB  - Non-CNS chemokine production may contribute to previously unrecognised components
      of Multiple Sclerosis (MS) pathology. Here we show that IL-8, a neutrophil
      chemoattractant, is significantly increased in serum from individuals with MS,
      and that the rodent homolog of IL-8 (CXCL1) is expressed in the liver in
      experimental autoimmune encephalomyelitis (EAE), a rodent model of MS. The
      hepatic expression of CXCL1 in EAE is accompanied by neutrophil recruitment to
      the liver, and we show that this recruitment is a feature of post mortem liver
      tissue from MS patients, which is a previously unrecognised phenomenon. We
      speculated that the presence of peripheral CXC-chemokine expression might
      contribute to the sickness behaviours associated with MS, which are a significant
      contributor to morbidity. Peripheral, but not central, administration of CXCL1 to
      Wistar rats inhibited spontaneous activity in the open field and burrowing
      behaviour in a dose-dependent manner (5-45 microg). The expression of CXCL1 by
      the liver and the recruitment of neutrophils can be modelled by the intracerebral
      injection of IL-1beta. Here, we found that interferon-beta (IFN-beta)
      pretreatment significantly inhibited hepatic CXCL1 production and neutrophil
      recruitment to the liver induced by the microinjection of IL-1beta into the
      brain. Thus while the mechanism by which IFN-beta therapy suppresses disease in
      MS remains unclear, the data presented here suggests that the inhibition of
      hepatic chemokine synthesis may be a contributing factor.

PMID- 20138140
TI  - Neuro-immune, behavioral and molecular aspects of brain damage.

PMID- 20138141
TI  - Treatment with the catalytic metalloporphyrin AEOL 10150 reduces inflammation and
      oxidative stress due to inhalation of the sulfur mustard analog 2-chloroethyl
      ethyl sulfide.
AB  - Sulfur mustard (bis-2-(chloroethyl) sulfide; SM) is a highly reactive vesicating
      and alkylating chemical warfare agent. A SM analog, 2-chloroethyl ethyl sulfide
      (CEES), has been utilized to elucidate mechanisms of toxicity and as a screen for
      therapeutics. Previous studies with SM and CEES have demonstrated a role for
      oxidative stress as well as decreased injury with antioxidant treatment. We
      tested whether posttreatment with the metalloporphyrin catalytic antioxidant AEOL
      10150 would improve outcome in CEES-induced lung injury. Anesthetized rats
      inhaled 5% CEES for 15 min via a nose-only inhalation system. At 1 and 9 h after
      CEES exposure, rats were given AEOL 10150 (5 mg/kg, sc). At 18 h post-CEES
      exposure BALF lactate dehydrogenase activity, protein, IgM, red blood cells, and
      neutrophils were elevated but were decreased by AEOL 10150 treatment. Lung
      myeloperoxidase activity was increased after CEES inhalation and was ameliorated
      by AEOL 10150. The lung oxidative stress markers 8-OHdG and 4-HNE were elevated
      after CEES exposure and significantly decreased by AEOL 10150 treatment. These
      findings demonstrate that CEES inhalation increased lung injury, inflammation,
      and oxidative stress, and AEOL 10150 was an effective rescue agent. Further
      investigation utilizing catalytic antioxidants as treatment for SM inhalation
      injury is warranted.

PMID- 20138142
TI  - Frog skins keep redox homeostasis by antioxidant peptides with rapid radical
      scavenging ability.
AB  - The question of how amphibians can protect themselves from reactive oxygen
      species when exposed to the sun in an oxygen-rich atmosphere is important and
      interesting, not only from an evolutionary viewpoint, but also as a primer for
      researchers interested in mammalian skin biology, in which such peptide systems
      for antioxidant defense are not well studied. The identification of an
      antioxidant peptide named antioxidin-RL from frog (Odorrana livida) skin in this
      report supports the idea that a peptide antioxidant system may be a widespread
      antioxidant strategy among amphibian skins. Its ability to eliminate most of the
      2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical tested within 2 s,
      which is much faster than the commercial antioxidant factor butylated
      hydroxytoluene, suggests that it has a potentially large impact on redox
      homeostasis in amphibian skins. Cys10 is proven to be responsible for its rapid
      radical scavenging function and tyrosines take part in the binding of antioxidin
      RL to radicals according to our nuclear magnetic resonance assay.

PMID- 20138143
TI  - Cytoprotective induction of nitric oxide synthase in a cellular model of 5
      aminolevulinic acid-based photodynamic therapy.
AB  - Photodynamic therapy (PDT) employs a photosensitizing agent, molecular oxygen,
      and visible light to generate reactive species that kill tumor and tumor
      vasculature cells. Nitric oxide produced by these cells could be procarcinogenic
      by inhibiting apoptosis or promoting angiogenesis and tumor growth. The purpose
      of this study was to determine whether tumor cells upregulate NO as a
      cytoprotective measure during PDT. Breast tumor COH-BR1 cells sensitized in their
      mitochondria with 5-aminolevulinic acid (ALA)-derived protoporphyrin IX died
      apoptotically after irradiation, ALA- and light-only controls showing no effect.
      Western analysis revealed that inducible nitric oxide synthase (iNOS) was
      upregulated >3-fold within 4 h after ALA/light treatment, whereas other NOS
      isoforms were unaffected. Exposing cells to a NOS inhibitor (L-NAME or 1400W)
      during photochallenge enhanced caspase-3/7 activation and apoptotic killing up to
      2- to 3-fold while substantially reducing chemiluminescence-assessed NO
      production, suggesting that this NO was cytoprotective. Consistently, the NO
      scavenger cPTIO enhanced ALA/light-induced caspase-3/7 activation and apoptotic
      kill by >2.5-fold. Of added significance, cells could be rescued from 1400W
      exacerbated apoptosis by an exogenous NO donor, spermine-NONOate. This is the
      first reported evidence for increased tumor cell resistance due to iNOS
      upregulation in a PDT model. Our findings indicate that stress-elicited NO in PDT
      treated tumors could compromise therapeutic efficacy and suggest NOS-based
      pharmacologic interventions for preventing this.

PMID- 20138145
TI  - WITHDRAWN: The scientific legacy of Jacques Monod.

PMID- 20138144
TI  - A systematic assessment of automated ribosomal intergenic spacer analysis (ARISA)
      as a tool for estimating bacterial richness.
AB  - ARISA (automated ribosomal intergenic spacer analysis) is a commonly used method
      for microbial community analysis that provides estimates of microbial richness
      and diversity. Here we investigated the potential biases of ARISA in richness
      estimation by performing computer simulations using 722 complete genomes. Our
      simulations based on in silico PCR demonstrated that over 8% of bacterial strains
      represented by complete genomes will never yield a PCR fragment using ARISA
      primers, usually because their ribosomal RNA genes are not organized in an
      operon. Despite the tendency of ARISA to overestimate species richness, a strong
      linear correlation exists between the observed number of fragments, even after
      binning, and the actual number of species in the sample. This linearity is fairly
      robust to the taxon sampling in the database as it is also observed on subsets of
      the 722 genome database using a jackknife approach. However, this linearity
      disappears when the species richness is high and binned fragment lengths
      gradually become saturated. We suggest that for ARISA-based richness estimates,
      where the number of binned lengths observed ranges between 10 and 116, a
      correction should be used in order to obtain more accurate "species richness"
      results comparable to 16S rRNA clone-library data.

PMID- 20138146
TI  - Effects of Azospirillum brasilense with genetically modified auxin biosynthesis
      gene ipdC upon the diversity of the indigenous microbiota of the wheat
      rhizosphere.
AB  - The phytostimulatory properties of Azospirillum inoculants, which entail
      production of the phytohormone indole-3-acetic acid (IAA), can be enhanced by
      genetic means. However, it is not known whether this could affect their
      interactions with indigenous soil microbes. Here, wheat seeds were inoculated
      with the wild-type strain Azospirillum brasilense Sp245 or one of three
      genetically modified (GM) derivatives and grown for one month. The GM derivatives
      contained a plasmid vector harboring the indole-3-pyruvate/phenylpyruvate
      decarboxylase gene ipdC (IAA production) controlled either by the constitutive
      promoter PnptII or the root exudate-responsive promoter PsbpA, or by an empty
      vector (GM control). All inoculants displayed equal rhizosphere population
      densities. Only inoculation with either ipdC construct increased shoot biomass
      compared with the non-inoculated control. At one month after inoculation,
      automated ribosomal intergenic spacer analysis (ARISA) revealed that the effect
      of the PsbpA construct on bacterial community structure differed from that of the
      GM control, which was confirmed by 16S rDNA-based denaturing gradient gel
      electrophoresis (DGGE). The fungal community was sensitive to inoculation with
      the PsbpA construct and especially the GM control, based on ARISA data. Overall,
      fungal and bacterial communities displayed distinct responses to inoculation of
      GM A. brasilense phytostimulators, whose effects could differ from those of the
      wild-type.

PMID- 20138147
TI  - Interaction between cartilage oligomeric matrix protein and extracellular matrix
      protein 1 mediates endochondral bone growth.
AB  - In an effort to define the biological functions of COMP, a functional genetic
      screen was performed. This led to the identification of extracellular matrix
      protein 1 (ECM1) as a novel COMP-associated partner. COMP directly binds to ECM1
      both in vitro and in vivo. The EGF domain of COMP and the C-terminus of ECM1
      mediate the interaction between them. COMP and ECM1 colocalize in the growth
      plates invivo. ECM1 inhibits chondrocyte hypertrophy, matrix mineralization, and
      endochondral bone formation, and COMP overcomes the inhibition by ECM1. In
      addition, COMP-mediated neutralization of ECM1 inhibition depends on their
      interaction, since COMP largely fails to overcome the ECM1 inhibition in the
      presence of the EGF domain of COMP, which disturbs the association of COMP and
      ECM1. These findings provide the first evidence linking the association of COMP
      and ECM1 and the biological significance underlying the interaction between them
      in regulating endochondral bone growth.

PMID- 20138148
TI  - D1 receptors play a major role in the dopamine modulation of mouse ileum
      contractility.
AB  - Since the role of dopamine in the bowel motility is far from being clear, our aim
      was to analyse pharmacologically the effects of dopamine on mouse ileum
      contractility. Contractile activity of mouse ileum was examined in vitro as
      changes in isometric tension. Dopamine caused a concentration-dependent reduction
      of the spontaneous contraction amplitude of ileal muscle up to their complete
      disappearance. SCH-23390, D1 receptor antagonist, which per se increased basal
      tone and amplitude of spontaneous contractions, antagonized the responses to
      dopamine, whilst sulpiride or domperidone, D2 receptor antagonists, were without
      effects. The application of both D1 and D2 antagonists had additive effects. SKF
      38393, D1 receptor agonist, mimicked dopamine-induced effects. Dopamine responses
      were insensitive to tetrodotoxin, atropine, nitric oxide synthase inhibitor or
      adenosine receptor antagonists, but they were reduced by adenylyl cyclase
      inhibition or apamin. Dopamine at a concentration which did not cause a
      significant reduction of phasic contractions inhibited the cholinergic
      contractions in response to field stimulation. SCH-23390 per se induced an
      increase of the neural cholinergic contraction and antagonized the dopamine
      effects, whilst sulpiride or domperidone did not. The application of D1 and D2
      antagonists had additive effects. In conclusion, mouse ileum is under basal
      inhibitory control by dopamine, through D1 receptor activation, linked to
      adenylyl cyclase and activation of apamin-sensitive potassium channels. An
      agonistic interaction of the dopamine receptor subtypes in the regulation
      intestinal contractility has being also highlighted. This study would provide new
      insight on the pharmacology of the modulation of the gastrointestinal
      contractility by dopamine.

PMID- 20138149
TI  - Microinjection of Xenopus laevis oocytes as a system for studying nuclear
      transport of viruses.
AB  - Microinjection of Xenopus laevis oocytes is an excellent system for studying
      nuclear transport because of the large size of the oocyte and its high nuclear
      pore complex (NPC) density. In addition, the fact that Xenopus oocytes are not
      permissive for most mammalian viruses makes this system especially useful for
      studying nuclear transport of viruses in the absence of the confounding factor of
      virus replication. In this article, we briefly discuss the contribution of
      microinjection of Xenopus oocytes to the field of nuclear transport. We then
      describe the protocols we have developed using microinjection of Xenopus oocytes
      to study nuclear transport of viral capsids, and summarize variations of the
      technique that can be used to address many different questions about the nuclear
      transport of viruses.

PMID- 20138150
TI  - Bacillus licheniformis Anti-TRAP can assemble into two types of dodecameric
      particles with the same symmetry but inverted orientation of trimers.
AB  - Anti-TRAP (AT) protein regulates expression of tryptophan biosynthetic genes by
      binding to the trp RNA-binding attenuation protein (TRAP) and preventing its
      interaction with RNA. Bacillus subtilis AT forms trimers that can either interact
      with TRAP or can further assemble into dodecameric particles. To determine which
      oligomeric forms are preserved in AT proteins of other Bacilli we studied
      Bacillus licheniformis AT which shares 66% sequence identity with the B. subtilis
      protein. We show that in solution B. licheniformis AT forms stable trimers. In
      crystals, depending on pH, such trimers assemble into two different types of
      dodecameric particles, both having 23 point group symmetry. The dodecamer formed
      at pH 6.0 has the same conformation as previously observed for B. subtilis AT.
      This dodecamer contains a large internal chamber with the volume of approximately
      700 A(3), which is lined by the side chains of twelve valine residues. The
      presence of the hydrophobic chamber hints at the possibility that the dodecamer
      formation could be induced by binding of a ligand. Interestingly, in the
      dodecamer formed at pH 8.0 all trimers are turned inside out relatively to the
      form observed at pH 6.0.

PMID- 20138151
TI  - We remember the good things: Age differences in learning and memory.
AB  - We combined a feedback-based learning task with a recognition memory paradigm to
      investigate how reward-based learning affects the event-related potential (ERP)
      correlates of recognition memory in younger and older adults. We found that
      positive, but not negative learning improves memory and results in an increased
      early ERP old-new effect, which is typically associated with familiarity-based
      memory. This indicates that reward-based learning supports a fast and relatively
      automatic memory retrieval process. Furthermore, we found age-related impairments
      in reward-based learning, whereas memory for the learned information was intact
      in the elderly, suggesting that declarative memory might be less affected by
      aging.

PMID- 20138152
TI  - Scaling of muscle metabolic enzymes: an historical perspective.
AB  - In this paper, we take an historical approach to reviewing research into the
      patterns of metabolic enzymes in muscle in relation to body size, focusing on
      mitochondrial enzymes. One of the first studies on allometric scaling of muscle
      enzymes was published in an early issue of this journal (George and Talesara,
      1961 Comp. Biochem. Physiol. 3: 267-273). These researchers studied a number of
      locally available birds and a bat, measuring the activity of the mitochondrial
      enzyme succinate dehydrogenase in relation to body mass and muscle structure.
      Though the phenomenon of allometric scaling of metabolism was well recognized
      even 50 years earlier, this study was one of the first to explore the enzymatic
      underpinnings of the metabolic patterns in different animals. In this review, we
      begin by considering the George and Talesara study in the context of this early
      era in metabolic biochemistry and comparative physiology. We review subsequent
      studies in the last 50 years that continued the comparative analysis of enzyme
      patterns in relation to body size in diverse experimental models. This body of
      work identified a recurrent (though not ubiquitous) reciprocal relationship
      between oxidative and glycolytic enzymes. In the last 10 years, studies have
      focused on identifying the molecular mechanisms that determine the muscle
      metabolic enzyme phenotype.

PMID- 20138153
TI  - Mechanisms of inflammation.

PMID- 20138154
TI  - Hirsutenone inhibits lipopolysaccharide-activated NF-kappaB-induced inflammatory
      mediator production by suppressing Toll-like receptor 4 and ERK activation.
AB  - Microbial products, including lipopolysaccharide, may be involved in the
      pathogenesis of skin diseases such as atopic dermatitis. Diarylheptanoids such as
      oregonin and hirsutenone have been shown to have an anti-inflammatory effect. We
      investigated the effect of hirsutenone on lipopolysaccharide-induced inflammatory
      mediator production in keratinocytes in relation to the Toll-like receptor 4
      mediated activation of the extracellular signal-regulated kinase (ERK) and
      nuclear factor (NF)-kappaB pathways. Hirsutenone, dexamethasone, ERK inhibitor or
      Bay 11-7085 (an inhibitor of NF-kappaB activation) reduced the lipopolysaccharide
      induced production of cytokines IL-1beta and IL-8, and the chemokine CCL17.
      Hirsutenone, ERK inhibitor or Bay 11-7085 also prevented the lipopolysaccharide
      induced expression of Toll-like receptor 4, the phosphorylation of inhibitory
      kappaB-alpha, the activation of NF-kappaB and the expression of ERK. The results
      show that hirsutenone may reduce the lipopolysaccharide-stimulated production of
      inflammatory mediators in keratinocytes by suppressing the Toll-like receptor 4
      expression-mediated NF-kappaB activation that is regulated by the ERK pathway.
      These findings suggest that hirsutenone may exert a preventive effect against
      microbial endotoxin lipopolysaccharide-induced inflammatory skin diseases through
      inhibition of ERK pathway-mediated NF-kappaB activation.

PMID- 20138155
TI  - Biphasic positive effect of formononetin on metabolic activity of human normal
      and osteoarthritic subchondral osteoblasts.
AB  - Osteoarthritis is a multifactorial disease characterized by loss of articular
      cartilage and subchondral plate thickening. Therefore, biochemical analysis of
      the underlying bone tissue has provided important information for treatment of
      osteoarthritis. In this study, we determined the potential role of formononetin,
      a phytoestrogen isolated from Astragalus membranaceus to alter the expression of
      metabolic markers and cytokine production of human normal osteoblasts (Obs) and
      osteoarthritis subchondral osteoblasts (OA Obs). Human OA Obs and normal Obs were
      cultured for 3days, 7days or 14days in the present medium only or were treated
      with various doses of formononetin. Cells were analyzed for viability by WST-8
      assay, alkaline phosphatase (ALP) activity, osteogenic markers (osteocalcin (OCN)
      and type I collagen (Col I)) and cytokines (interleukin-6 (IL-6), vascular
      endothelial growth factor (VEGF), bone morphogenic protein-2 (BMP-2)). The level
      of IL-6, VEGF, BMP-2, OCN and Col I was increased in OA Obs compared with normal
      Obs. Formononetin dose-dependently decreased ALP, IL-6, VEGF, BMP-2, OCN and Col
      I in OA Obs, while markedly increased ALP, VEGF, BMP-2, OCN and Col I in normal
      Obs. Interestingly, formononetin markedly increased the expression of VEGF and
      BMP-2 for 3days of culture and significantly increased OCN and Col I at 14days in
      human normal Obs. The remodeling effect of formononetin on osteogenic markers and
      cytokines of inflammatory mediators was more striking in OA Obs as well. Taken
      together, these results could suggest that formononetin has biphasic positive
      effects on normal Obs and OA Obs by modifying their biological synthetic
      capacities.

PMID- 20138156
TI  - Arsenic trioxide induces endoplasmic reticulum stress-related events in
      neutrophils.
AB  - We recently reported that the endoplasmic reticulum (ER)-induced cell pathway of
      apoptosis is operational in human neutrophils and that some ER stressors can
      accelerate this process. Recent data suggest that arsenic trioxide (As(2)O(3) or
      ATO), may also act as an ER stressor. The aims of the present study were to
      elucidate if other ER stress-related events occur in ATO-induced neutrophils, and
      to determine the role of caspase-4 in the proapoptotic activity of ATO. We found
      that ATO induced ubiquitination of proteins, and increased calcium concentration
      and gene expression of calcineurin in neutrophils. In addition to caspase-4,
      activities of caspase-3, -8 and -9 were increased by ATO. The processing of
      caspase-4 was reversed by a caspase-8 inhibitor, indicating that caspase-4
      activation requires the action of upstream initiator components, questioning on
      the role of caspase-4 in ATO-induced ER stress-mediated cell apoptosis. Using
      caspase-4 deficient THP-1 cells, we demonstrated that the proapoptotic effect of
      ATO was similar to that of control caspase-4-positive cells. We conclude that ATO
      is an ER stressor that can induce cell apoptosis by a mechanism which does not
      require caspase-4. In addition, we conclude that caspase-4 activation in ATO
      induced neutrophils could be involved in functions other than apoptosis.

PMID- 20138157
TI  - Effect of thoracic gas compression and bronchodilation on the assessment of
      expiratory flow limitation during exercise in healthy humans.
AB  - Expiratory flow limitation (EFL) during exercise may be overestimated or falsely
      detected when superimposing tidal breaths within a pre-exercise maximal
      expiratory flow volume (MEFV) curve due to thoracic gas compression (TGC) and
      bronchodilation. Accordingly, the purpose of this study was to determine the
      effects of TGC and bronchodilation on the assessment of EFL in 35 healthy
      subjects. A pre-exercise forced vital capacity (FVC) maneuver was performed that
      did not account for TGC (MEFV(pre)). Subjects then performed graded expirations
      from total lung capacity to residual volume at different efforts to account for
      TGC (MEFV(pre-TGC)). Post-exercise FVC (MEFV(post)) and post-exercise graded
      expirations (MEFV(post-TGC)) were performed to account for bronchodilation and
      TGC. EFL occurred in 29 subjects when using MEFV(pre). The magnitude of EFL in
      these subjects was 47+/-23% which was significantly higher than MEFV(pre-TGC)
      (28+/-28%), MEFV(post) (24+/-27%) and MEFV(post-TGC) (19+/-24%) (P<0.00001).
      Using the traditional MEFV(pre) curve overestimates and falsely detects EFL since
      it does not account for TGC and bronchodilation.

PMID- 20138159
TI  - Antioxidant defence systems and generation of reactive oxygen species in
      osteosarcoma cells with defective mitochondria: effect of selenium.
AB  - Mitochondrial diseases originate from mutations in mitochondrial or nuclear genes
      encoding for mitochondrial proteome. Neurogenic muscle weakness, ataxia and
      retinitis pigmentosa (NARP) syndrome is associated with the T8993G transversion
      in ATP6 gene which results in substitution at the very conservative site in the
      subunit 6 of mitochondrial ATP synthase. Defects in the mitochondrial respiratory
      chain and the ATPase are considered to be accompanied by changes in the
      generation of reactive oxygen species (ROS). This study aimed to elucidate
      effects of selenium on ROS and antioxidant system of NARP cybrid cells with 98%
      of T8993G mutation load. We found that selenium decreased ROS generation and
      increased the level and activity of antioxidant enzymes such as glutathione
      peroxidase (GPx) and thioredoxin reductase (TrxR). Therefore, we propose selenium
      to be a promising therapeutic agent not only in the case of NARP syndrome but
      also other diseases associated with mitochondrial dysfunctions and oxidative
      stress.

PMID- 20138160
TI  - Antisense repression of sucrose phosphate synthase in transgenic muskmelon alters
      plant growth and fruit development.
AB  - To unravel the roles of sucrose phosphate synthase (SPS) in muskmelon (Cucumis
      melo L.), we reduced its activity in transgenic muskmelon plants by an antisense
      approach. For this purpose, an 830 bp cDNA fragment of muskmelon sucrose
      phosphate synthase was expressed in antisense orientation behind the 35S promoter
      of the cauliflower mosaic virus. The phenotype of the antisense plants clearly
      differed from that of control plants. The transgenic plant leaves were markedly
      smaller, and the plant height and stem diameter were obviously shorter and
      thinner. Transmission electron microscope observation revealed that the membrane
      degradation of chloroplast happened in transgenic leaves and the numbers of grana
      and grana lamella in the chloroplast were significantly less, suggesting that the
      slow growth and weaker phenotype of transgenic plants may be due to the damage of
      the chloroplast ultrastructure, which in turn results in the decrease of the net
      photosynthetic rate. The sucrose concentration and levels of sucrose phosphate
      synthase decreased in transgenic mature fruit, and the fruit size was smaller
      than the control fruit. Together, our results suggest that sucrose phosphate
      synthase may play an important role in regulating the muskmelon plant growth and
      fruit development.

PMID- 20138158
TI  - Conserved and divergent features of the structure and function of La and La
      related proteins (LARPs).
AB  - Genuine La proteins contain two RNA binding motifs, a La motif (LAM) followed by
      a RNA recognition motif (RRM), arranged in a unique way to bind RNA. These
      proteins interact with an extensive variety of cellular RNAs and exhibit
      activities in two broad categories: i) to promote the metabolism of nascent pol
      III transcripts, including precursor-tRNAs, by binding to their common, UUU-3'OH
      containing ends, and ii) to modulate the translation of certain mRNAs involving
      an unknown binding mechanism. Characterization of several La-RNA crystal
      structures as well as biochemical studies reveal insight into their unique two
      motif domain architecture and how the LAM recognizes UUU-3'OH while the RRM binds
      other parts of a pre-tRNA. Recent studies of members of distinct families of
      conserved La-related proteins (LARPs) indicate that some of these harbor activity
      related to genuine La proteins, suggesting that their UUU-3'OH binding mode has
      been appropriated for the assembly and regulation of a specific snRNP (e.g., 7SK
      snRNP assembly by hLARP7/PIP7S). Analyses of other LARP family members suggest
      more diverged RNA binding modes and specialization for cytoplasmic mRNA-related
      functions. Thus it appears that while genuine La proteins exhibit broad general
      involvement in both snRNA-related and mRNA-related functions, different LARP
      families may have evolved specialized activities in either snRNA or mRNA-related
      functions. In this review, we summarize recent progress that has led to greater
      understanding of the structure and function of La proteins and their roles in
      tRNA processing and RNP assembly dynamics, as well as progress on the different
      LARPs.

PMID- 20138161
TI  - Initial brain lesion size affects the extent of subsequent pathophysiological
      responses.
AB  - The severity of an ischemic stroke is variable in patients, because the occlusion
      position on the artery and the territory of distal vessels are individual.
      However, the relationship between the extent of initial brain lesion and the
      subsequent pathophysiological responses is poorly understood. Here, we studied
      the effects of the initial brain lesion size on the subsequent pathophysiological
      responses by using a photochemically induced thrombotic brain damage (PIT-BD)
      model, in which the brain lesion size can be well-reproducibly controlled than
      that induced by a middle cerebral artery occlusion (MCA-O) model. In the PIT-BD
      model, a large lesion, which comprised 4.9% of the whole brain on day 3, showed a
      56% reduction until day 7. However, a small lesion, which comprised 1.3% of the
      whole brain, showed a 30% reduction. In addition, on day 5, the activation of
      both microglia and astrocytes was lesser in mice with small lesions than in mice
      with large lesions. Furthermore, we found that, smaller lesions in mice lacking
      gene of urokinase-receptor (uPAR(-/-)) than wild type (uPAR(+/+)) mice on day 3
      showed less reduction until day 7 in MCA-O model, whereas lesions with comparable
      size in uPAR(-/-) mice showed comparable reduction with uPAR(+/+) mice in PIT-BD
      model. Thus it was indicated that the less reduction of the lesions in uPAR(-/-)
      mice in the MCA-O model did not result from the deficient gene but the difference
      of the initial lesion size. These findings suggested that the more severe the
      brain damage, the stronger the subsequent pathophysiological responses.

PMID- 20138162
TI  - Influence of CGS 21680, a selective adenosine A(2A) receptor agonist, on NMDA
      receptor function and expression in the brain of Huntington's disease mice.
AB  - The effect of chronic treatment with the selective adenosine A(2A) receptor
      agonist CGS 21680 on N-Methyl-d-Aspartate (NMDA) receptor function and expression
      has been studied in the striatum and cortex of R6/2 mice, a genetic mouse model
      of Huntington's disease (HD). Starting from 8weeks of age, R6/2 and wild type
      (WT) mice were treated daily with CGS 21680 (0.5mg/kg i.p.) for 3weeks and the
      expression levels of NMDA receptor subunits were then evaluated. In addition, to
      study CGS 21680-induced changes in NMDA receptor function, NMDA-induced toxicity
      in corticostriatal slices from both R6/2 and WT mice was investigated. We found
      that CGS 21680 increased NR2A subunit expression and the NR2A/NR2B ratio in the
      cortex of R6/2 mice, having no effect in WT mice. In the striatum, CGS 21680
      reduced NR1 expression in both R6/2 and WT mice while the effect on NR2A and
      NR2/NR2B expression was genotype-dependent, reducing and increasing their
      expression in WT and R6/2 mice, respectively. On the contrary, NMDA-induced
      toxicity in corticostriatal slices was not modified by the treatment in WT or HD
      mice. These results demonstrate that in vivo activation of A(2A) receptors
      modulates the subunit composition of NMDA receptors in the brain of HD mice.

PMID- 20138163
TI  - Arcuate nucleus destruction does not block food deprivation-induced increases in
      food foraging and hoarding.
AB  - The mechanisms underlying the control of food intake are considerably better
      understood than those underlying the appetitive ingestive behaviors of foraging
      and hoarding of food, despite the prevalence of the latter across species
      including humans. Neuropeptide Y (NPY) and Agouti-related protein (AgRP), two
      orexigenic neuropeptides known to stimulate food intake in a variety of species,
      applied centrally to Siberian hamsters increases foraging and especially hoarding
      with lesser increases in food intake. Both are expressed in the arcuate nucleus
      (Arc) and their synthesis increases with food deprivation, a naturally-occurring
      stimulus that markedly increases foraging and hoarding in Siberian hamsters.
      Therefore, we tested whether destruction of Arc neurons blocks these ingestive
      behaviors. This was accomplished either by microinjecting NPY conjugated to
      saporin (NPY-SAP) bilaterally into the Arc to kill NPY receptor-bearing neurons
      or via neonatal monosodium glutamate (MSG) treatment. For both methods, Arc
      cresyl violet staining (cell density) and NPY and Y1 receptor-immunoreactivity
      (ir) were significantly decreased. Although baseline foraging and food hoarding
      were not affected, food deprivation-induced increased food hoarding was
      surprisingly exaggerated approximately 100% with both types of Arc destruction.
      We found a substantial amount of remaining NPY-ir fibers, likely emanating from
      the brainstem, and a significant up-regulation of Y1 receptors in Arc NPY
      projections areas (hypothalamic paraventricular nucleus and perifornical area)
      after Arc denervation and their activation may have accounted for the exaggerated
      increases. The converging evidence from both Arc destruction methods suggests an
      intact Arc is not necessary for food deprivation-induced increases in food
      foraging and hoarding.

PMID- 20138164
TI  - Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of
      focal cerebral ischemia reperfusion.
AB  - Inflammation, which is known to be detrimental to the neurological outcome during
      the acute phase after ischemia, provides a potential preventative or therapeutic
      approach for acute stroke. Lipoxins are endogenous lipoxygenase derived
      eicosanoids and evokes protective actions in a range of pathophysiologic
      processes. Here, we evaluated the efficacy of 5 (S), 6 (R)-lipoxin A(4) methyl
      ester (LXA(4) ME), a stable synthetic analogue of lipoxin A(4) in cerebral
      ischemia reperfusion injury in rats. Transient focal cerebral ischemia was
      induced by middle cerebral artery occlusion for 2h. Intracerebroventricular
      administration of LXA(4) ME immediately after onset of ischemia ameliorated
      neurological dysfunctions, reduced infarction volume and attenuated neuronal
      apoptosis. Moreover, Treatment with LXA(4) ME suppressed neutrophils infiltration
      and lipid peroxidation levels; inhibited the activation of microglia and
      astrocytes; reduced the expression of pro-inflammatory cytokines TNF-alpha and IL
      1beta; and up-regulated the expression of anti-inflammatory cytokines IL-10 and
      TGF-beta1 in the ischemic brain. In addition, activation of NF-kappaBeta was
      inhibited by LXA(4) ME treatment. These results demonstrate that treatment of
      LXA(4) ME affords strong neuroprotective effect against cerebral ischemia
      reperfusion injury, and that these effects might be associated with its anti
      inflammatory property.

PMID- 20138165
TI  - Motor preparation is modulated by the resolution of the response timing
      information.
AB  - In the present experiment, the temporal predictability of response time was
      systematically manipulated to examine its effect on the time course of motor pre
      programming and release of the intended movement by an acoustic startle stimulus.
      Participants performed a ballistic right wrist extension task in four different
      temporal conditions: 1) a variable foreperiod simple RT task, 2) a fixed
      foreperiod simple RT task, 3) a low resolution countdown anticipation-timing
      task, and 4) a high resolution anticipation-timing task. For each task, a
      startling acoustic stimulus (124dB) was presented at several intervals prior to
      the "go" signal ("go" -150ms, -500ms, and -1500ms). Results from the startle
      trials showed that the time course of movement pre-programming was affected by
      the temporal uncertainty of the imperative "go" cue. These findings demonstrate
      that the resolution of the timing information regarding the response cue has a
      marked effect on the timing of movement preparation such that under conditions of
      low temporal resolution, participants plan the movement well in advance in
      accordance with the anticipated probability of onset of the cue, whereas movement
      preparation is delayed until less than 500ms prior to response time when
      continuous temporal information is provided.

PMID- 20138166
TI  - Antibodies to fibrillarin, PM-Scl and RNA polymerase III detected by ELISA assays
      in patients with systemic sclerosis.
AB  - BACKGROUND: Anti-fibrillarin (AFA), anti-RNA polymerase (anti-RNAP), and anti-PM
      Scl autoantibodies are useful markers for the diagnosis of systemic sclerosis
      (SSc) in patients who are anti-centromere- (ACA) or anti-topoisomerase I (anti
      topo I)-negative, but, until recently, the only specific method for their
      identification was the radio-immunoprecipitation assay. The aim of this study was
      to evaluate the clinical accuracy of the new enzyme-linked immunosorbent assays
      (ELISA) developed by Phadia for their detection. METHODS: Sera of 50 ACA and anti
      topo I-negative SSc patients, and, as control group, sera of 122 patients (42
      with SSc, ACA or anti-topo I-positive, 40 with systemic lupus erythematosus and
      40 with rheumatoid arthritis) were studied. RESULT: Using the cutoff proposed by
      the manufacturer (10 AU/mL), sensitivity and specificity were: for AFA, 22% and
      92.6%; for anti-RNAP, 16% and 97.5%; and for anti-PM-Scl, 8% and 98.8%,
      respectively. Using a cutoff corresponding to 98.8% specificity for all three
      antibodies, sensitivity was 10%, 14% and 8%, respectively. The combined use of
      these three antibody assays enabled identification of 32% of ACA- and anti-topo I
      negative SSc patients. CONCLUSIONS: These new ELISA methods for AFA, anti-RNAP
      III and anti-PM-Scl detection have good diagnostic specificity, and may help
      identify a subset of SSc patients ACA and anti-topo I-negative.

PMID- 20138167
TI  - The prevalence of microalbuminuria and its relationships with the components of
      metabolic syndrome in the general population of China.
AB  - BACKGROUND: Few studies have examined the relationships between the prevalence of
      microalbuminuria and the metabolic risk factors in the general population of
      China. We performed a population based study to investigate the prevalence of
      microalbuminuria and its relationships with the components of the metabolic
      syndrome in Hangzhou, China. METHODS: The subjects of this cross-sectional study
      were the individuals from 19 to 87 y. The metabolic syndrome was defined based on
      the criteria of the Chinese Diabetes Society (CDS). Microalbuminuria was defined
      as a urine albumin-creatinine ratio of 30 to 300 mg/g. RESULTS: A total of 2985
      subjects (average age of 44 y) were analyzed. Among them, the prevalence of the
      metabolic syndrome and microalbuminuria was 12.6% and 8.8%, respectively.
      Microalbuminuria prevalence rate was significantly higher in the population >60 y
      than <60 y. The prevalence of MAU in the group with metabolic abnormalities was
      significantly higher than the control group, and the prevalence rate of MAU in
      the metabolic syndrome group reached up to 20.3%. There was a significantly
      positive correlation between the prevalence of microalbuminuria and the
      corresponding components of the metabolic syndrome (P<0.001). CONCLUSIONS:
      Microalbuminuria was highly prevalent in the middle-aged and elderly Chinese
      population in the city of Hangzhou. There is an increasing likelihood of having
      microalbuminuria if subjects have the metabolic syndrome. Early screening
      strategies for prevention and treatment of MAU are strongly suggested, especially
      in the population >60 y and the ones with metabolic abnormalities.

PMID- 20138168
TI  - Aberrant cytokines/chemokines production correlate with proteinuria in patients
      with overt diabetic nephropathy.
AB  - BACKGROUND: Diabetic nephropathy (DN) occurs in 20% to 30% of all patients with
      type 2 diabetes mellitus (DM) and is the most common cause of end-stage renal
      disease. However, the definite pathogenesis, especially the role of immune
      response, is still unclear. METHODS: We studied the production and expression of
      Th1 (IFN-gamma, IL-2R), Th2 (IL-4, IL-10), proinflammatory cytokines (IL-1beta,
      and TNF-alpha), and chemokines (MCP-1, and RANTES) in patients with DN. The
      correlation among cytokines, chemokines, and clinical parameters were examined.
      RESULTS: A patient with DN presented with longer disease duration, heavy
      proteinuria, and impaired renal function. Our results demonstrated increased
      proinflammatory cytokines, Th1 cytokines and chemokines, but not Th2 cytokines,
      in the plasma and urine of patients with DN as compared to patients with DM
      without overt nephropathy. Enhanced cytokine/chemokine activation in DN was also
      demonstrated by positive immunohistochemical staining of kidney tissue. We found
      a positive correlation between daily protein loss and plasma IFN-gamma and IL-2R,
      and urinary MCP-1, as well as a negative correlation between creatinine clearance
      and plasma TNF-alpha and urinary MCP-1. CONCLUSIONS: There were aberrant
      cytokines/chemokines production correlated with the degree of proteinuria in
      patient with overt DN and gross proteinuria. Inflammation may be important in the
      pathogenesis of DN.

PMID- 20138169
TI  - Optimization of cryopreservation condition for hematopoietic stem cells from
      umbilical cord blood.
AB  - The conditions for cryopreservation of CD34(+) hematopoietic stem cells (HSC)
      from umbilical cord blood (UCB) were optimized with a new cryo-medium containing
      10% ethylene glycol (EG) and 2% dimethyl sulfoxide (Me(2)SO) using a controlled
      rate freezing (CRF) method. After the cryopreservation of mononuclear cells (MNC)
      from UCB, recoveries of MNC, CD34(+) cells, and total colony-forming units (CFU)
      were significantly improved compared to those in the control cryo-medium
      containing 10% Me(2)SO and 2% Dextran-40 (P<0.05). This study shows that the new
      cryo-medium and CRF method provide better recoveries of MNC, HSC and total CFU
      than the control cryo-medium and isopropylalcohol freezing (IPA) method.
      Therefore, this cryo-medium, combined with the CRF method, is valuable for
      optimizing cryopreservation conditions for HSC from UCB to obtain satisfactory
      HSC recovery.

PMID- 20138170
TI  - Enhanced expression of lumican inhibited the attachment and growth of human
      embryonic kidney 293 cells.
AB  - Lumican is a member of a small leucine-rich proteoglycan (SLRP) family and it
      regulates the assembly and diameter of collagen fibers in the extracellular
      matrix of various tissues. Lumican expression was reported in various kinds of
      tumor cells. Lumican inhibits the growth of melanoma cells, but the lumican in
      pancreatic cancer correlated with an advanced stage and retroperitoneal and
      duodenal invasion. In this study, we clarified whether the enhanced expression of
      lumican contributes to cellular attachment, growth, colony formation, migration
      and invasion. HEK 293 cell, stably transfected with lumican cDNA synthesized and
      secreted a 50 kDa lumican protein at high levels in culture medium. The cells
      showed a polygonal appearance with long projections and the degree of adhesion of
      the cells to fibronectin was lower than that of empty vector transfected control
      cells (mock cells). In contrast, the degree of adhesion of the cells to type I
      collagen was not different from that of mock cells. The expression levels of
      alpha5 integrin, the major integrin subunit for fibronectin, were lower in
      lumican-transfected HEK cells than in mock cells. Furthermore, lumican
      transfected HEK cells showed reduced growth rates in vitro and did not form
      colonies in soft agar. Phosphorylation of AKT, extracellular signal-regulated
      kinase (ERK) 1/2 and mammalian target of rapamycin (mTOR) decreased in the
      lumican-transfected HEK cells. Cell migration and invasion were not altered in
      lumican-transfected HEK cells and mock cells. These findings indicate that the
      50kDa lumican protein plays important roles in the inhibition of HEK cell
      attachment and growth, and it might inhibit the activation of integrin pathways.

PMID- 20138171
TI  - CB1 receptor deficiency decreases wheel-running activity: consequences on
      emotional behaviours and hippocampal neurogenesis.
AB  - Chronic voluntary wheel-running activity has been reported to hypersensitise
      central CB1 receptors in mice. On the other hand, pharmacological findings
      suggest that the CB1 receptor could be involved in wheel-running behaviour and in
      running-induced neurogenesis in the hippocampus. We analysed wheel-running
      behaviour for 6 weeks and measured its consequences on hippocampal neurogenesis
      in CB1 knockout (CB1(-/-)) animals, compared to wild-type (CB1(+/+)) littermates.
      Because wheel running has been shown to affect locomotor reactivity in novel
      environments, memory for aversive events and depression-like behaviours, we also
      assessed these behaviours in control and running CB1(+/+) and CB1(-/-) mice. When
      compared with running CB1(+/+) mice, the distance covered weekly by CB1(-/-) mice
      was decreased by 30-40%, an observation accounted for by decreased time spent and
      maximal velocity on the wheels. Analyses of running distances with respect to the
      light/dark cycle revealed that mutant covered less distance throughout both the
      inactive and the active phases of that cycle. Locomotion in an activity cage,
      exploration in an open field, and immobility time in the forced swim test proved
      insensitive to chronic wheel running in either genotype. Wheel running, per se,
      did not influence the expression and extinction of cued fear memory but
      counteracted in a time-dependent manner the deficiency of extinction measured in
      CB1(-/-) mice. Hippocampal neurogenesis, assessed by doublecortin labelling of
      immature neurons in the dentate gyrus, was lowered by 40% in control CB1(-/-)
      mice, compared to control CB1(+/+) mice. Although CB1(-/-) mice ran less than
      their wild-type littermates, the 6-week running protocol increased neurogenesis
      to similar extents (37-39%) in both genotypes. This study suggests that mouse CB1
      receptors control wheel running but not its neurogenic consequences in the
      hippocampus.

PMID- 20138172
TI  - Current knowledge of the pre-autophagosomal structure (PAS).
AB  - Autophagy is a system for degradation of bulk cellular components in lytic
      compartments, vacuoles, or lysosomes when eukaryotic cells face with nutrient
      starvation. In this review, we focus on the pre-autophagosomal structure (PAS), a
      functional entity responsible for autophagosome formation in Saccharomyces
      cerevisiae, and discuss its relevance to autophagy in mammalian cells.

PMID- 20138173
TI  - Role of autophagy in Caenorhabditis elegans.
AB  - Autophagy is an evolutionarily conserved intracellular catabolic system. During
      Caenorhabditis elegans development, autophagy plays an important role in many
      physiological processes, including survival under starvation conditions,
      modulation of life span, and regulation of necrotic cell death caused by toxic
      ion-channel variants. Recently, it has been demonstrated that during
      embryogenesis, basal levels of autophagy selectively remove a group of proteins
      in somatic cells, including the aggregate-prone components of germline P
      granules. Degradation of these protein aggregates provides a genetic model to
      identify essential autophagy components and also to elucidate how the autophagic
      machinery selectively recognizes and degrades specific targets during animal
      development.

PMID- 20138174
TI  - BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived
      LMP1/CTAR1-induced NF-kappaB activation.
AB  - Epstein-Barr virus latent membrane protein 1 (LMP1) activates NF-kappaB signaling
      pathways through two C-terminal regions, CTAR1 and CTAR2. Previous studies have
      demonstrated that BS69, a multidomain cellular protein, regulates LMP1/CTAR2
      mediated NF-kappaB activation by interfering with the complex formation between
      TRADD and LMP1/CTAR2. Here, we found that BS69 directly interacted with the
      LMP1/CTAR1 domain and regulated LMP1/CTAR1-mediated NF-kappaB activation and
      subsequent IL-6 production. Regarding the mechanisms involved, we found that BS69
      directly interacted with TRAF3, a negative regulator of NF-kappaB activation.
      Furthermore, small-interfering RNA-mediated knockdown experiments revealed that
      TRAF3 was involved in the BS69-mediated suppression of LMP1/CTAR1-induced NF
      kappaB activation.

PMID- 20138175
TI  - Regional and temporal differences in leptin signaling in rat brain.
AB  - Leptin regulates energy homeostasis through activation of different hypothalamic
      pathways. Evidence indicates that leptin is a pleiotropic hormone that acts on
      many brain areas, altering food intake, metabolism, and locomotion, among other
      functions. Because short-term effects of leptin infusion and intracellular
      pathways in other brain areas involved in food regulation have not been
      thoroughly analysed, we have studied the acute effect of intracerebroventricular
      leptin administration on the levels of the long form of leptin receptor (Ob-Rb),
      as well as on activation of Janus kinase 2 (JAK2)-signal transducer and activator
      of transcription 3 (STAT3), protein kinase B (Akt), extracellular regulated
      kinases (ERKs) and levels of suppressor of cytokine signaling-3 (SOCS3) in the
      hypothalamus, hippocampus, frontal cortex and cerebellum of adult male Wistar
      rats at 15min, 1 and 6h. The levels of Ob-Rb increased at 6h in hypothalamus
      only. Leptin activated the JAK2/STAT3 pathway in all areas, although in a
      temporally specific pattern. In contrast, this hormone decreased Akt activation
      in hypothalamus, hippocampus and cerebellum and ERK activation in frontal cortex,
      while it increased ERK activation in hypothalamus and hippocampus. These
      differences in modulation of Ob-Rb levels and signaling indicate that the rapid
      effects of leptin in non-hypothalamic areas are mediated, at least in part,
      through the intracellular pathways involved in hypothalamic energy balance, but
      in a temporally specific manner.

PMID- 20138176
TI  - Changes in gene expression levels of somatolactin in the pituitary and morphology
      of gill mitochondria-rich cells in Mozambique tilapia after transfer to acidic
      freshwater (pH 3.5).
AB  - Mozambique tilapia, Oreochromis mossambicus, is easily acclimated to highly
      acidic water, and thus presents a useful model to unravel endocrine regulation of
      adaptation to acidic water in fish. We analyzed gene expression of somatolactin
      (sl), growth hormone (gh) and prolactin (prl), in the pituitary gland and size
      distribution of mitochondria-rich (MR) cells in the gills after transfer from
      normal freshwater (FW, pH 7.2) to acidified freshwater (AW, pH 3.5). Plasma
      osmolality drastically decreased until 2 days after transfer to AW, but had
      restored to normal after 1 week of acclimation, and this confirmed the excellent
      acid tolerance of tilapia. Expression levels of sl, gh and prl were all up
      regulated during short-term exposure to AW. The expression of sl remained
      elevated up to 7 days after transfer; the expression of gh and prl was back to
      initial levels at that time. These findings point to an important and specific
      role of SL in adaptation to acid water in this tilapia, although temporal
      contribution of GH and PRL cannot be ruled out. The size distribution of
      branchial MR cells changed drastically during acclimation to AW. The mean MR cell
      size was 1.5-fold larger in the fish exposed to AW for 7 days compared to
      controls in FW. The gills and their MR cells are a likely site of important acid
      base regulation, and SL may change ion-transport functions of MR cells to correct
      plasma osmotic balance disturbed by acid exposure.

PMID- 20138177
TI  - Insulin-like growth factor-3 (IGF-3) in male and female gonads of the tilapia:
      development and regulation of gene expression by growth hormone (GH) and 17alpha
      ethinylestradiol (EE2).
AB  - Recently, in addition to IGF-1 and IGF-2 the existence of a third form of IGF,
      termed IGF-3, limited to fishes, to be present only in the gonads and encoded by
      a separate gene has been reported. However, no further data have been presented
      on IGF-3. The present study on tilapia (Oreochromis niloticus) uses quantitative
      real-time PCR specific for tilapia IGF-1 and IGF-3. The organ distribution of IGF
      3 mRNA in adult fish and the early ontogeny of IGF-3 in male and female gonads
      were studied. The potential sensitivity of IGF-3 to GH was revealed by
      intraperitoneal injections of bream GH using IGF-1 as control gene. The effects
      of 17alpha-ethinylestradiol (EE2) exerted after feeding of high EE2 doses and
      exposure to low environmentally relevant EE2 doses on IGF-3 expression in testis
      and ovary during early development were determined. Low IGF-3 mRNA expression
      levels were detected in most organs studied, with the highest extra-gonadal
      amount in the pituitary. During development, the IGF-3 gene was significantly
      upregulated in male but downregulated in female gonad. Injections of GH elevated
      IGF-1 mRNA in male and female liver and ovary. IGF-3 did not respond to GH
      treatment neither in ovary nor in testis. Both EE2 treatments resulted in
      significant downregulations of IGF-3 mRNA in testis while ovarian IGF-3 mRNA did
      not respond. Thus, IGF-3 may be involved in reproduction of fishes most likely in
      the male gonad only. Whether IGF-3 also has some physiological significance in
      ovary or other organs should be the topic of further studies.

PMID- 20138178
TI  - Differential expression of three types of gonadotropin-releasing hormone genes
      during the spawning season in grass puffer, Takifugu niphobles.
AB  - Grass puffer, Takifugu niphobles, has unique spawning behavior; spawning occurs
      on beach only for several days around new moon and full moon from spring to early
      summer. To investigate the role of gonadotropin-releasing hormone (GnRH) in the
      reproductive function, genes encoding three types of GnRHs, namely seabream GnRH
      (sbGnRH), chicken GnRH-II (cGnRH-II) and salmon GnRH (sGnRH), were cloned and
      changes in their mRNA amounts were examined over the spawning season. In
      addition, changes in the pituitary gonadotropin subunit mRNAs and the plasma
      steroid hormones were examined over the spawning season. Fishes were assessed at
      four reproductive stages, i.e., in December (early maturation), in April
      (maturing), in May (spawning), and in July (post-spawning). Moreover, spawning
      fish just after releasing eggs and sperm were taken at a spawning bed. The
      amounts of sbGnRH mRNA were substantially elevated in May and the spawning fish
      in both sexes, concomitant with considerable elevations of follicle-stimulating
      hormone and luteinizing hormone beta subunit mRNAs and plasma estradiol-17beta
      (E(2)) and testosterone (T) levels. There were strong positive correlations
      between the sbGnRH mRNA and the plasma E(2) and T levels over the spawning season
      in both sexes. The amounts of cGnRH-II mRNA showed no noticeable changes except
      for an increase in the post-spawning females. The amounts of sGnRH mRNA in the
      males were significantly increased in May, but they were low in the spawning
      males. In the females, sGnRH mRNA increased from the maturing stage and reached a
      maximum in the post-spawning stage, in which a positive correlation with the
      plasma cortisol levels was observed. These specific changes suggest that the
      expression of three types of GnRH genes is differentially regulated during the
      spawning season, and sex steroids may be important for the differential
      expression of GnRH genes.

PMID- 20138179
TI  - Molecular and genetic studies suggest that thyroid hormone receptor is both
      necessary and sufficient to mediate the developmental effects of thyroid hormone.
AB  - Thyroid hormone (TH) affects diverse biological processes and can exert its
      effects through both gene regulation via binding the nuclear TH receptors (TRs)
      and non-genomic actions via binding to cell surface and cytoplasmic proteins. The
      critical importance of TH in vertebrate development has long been established,
      ranging from the formation of human cretins to the blockage of frog metamorphosis
      due the TH deficiency. How TH affects vertebrate development has been difficult
      to study in mammals due to the complications associated with the uterus-enclosed
      mammalian embryos. Anuran metamorphosis offers a unique opportunity to address
      such an issue. Using Xenopus as a model, we and others have shown that the
      expression of TRs and their heterodimerization partners RXRs (9-cis retinoic acid
      receptors) correlates temporally with metamorphosis in different organs in two
      highly related species, Xenopuslaevis and Xenopus tropicalis. In vivo molecular
      studies have shown that TR and RXR are bound to the TH response elements (TREs)
      located in TH-inducible genes in developing tadpoles of both species. More
      importantly, transgenic studies in X. laevis have demonstrated that TR function
      is both necessary and sufficient for mediating the metamorphic effects of TH.
      Thus, the non-genomic effects of TH have little or no roles during metamorphosis
      and likely during vertebrate development in general.

PMID- 20138180
TI  - The relationship between plasma steroid hormone concentrations and the
      reproductive cycle in the Northern Pacific rattlesnake, Crotalus oreganus.
AB  - We describe the reproductive cycle of Northern Pacific rattlesnakes (Crotalus
      oreganus) by quantifying steroid hormone concentrations and observing
      reproductive behaviors in free-ranging individuals. Additionally, we examined
      reproductive tissues from museum specimens. Plasma steroid hormone concentrations
      were quantified for both male and female snakes throughout the active season
      (March-October). We measured testosterone (T), 5alpha-dihydrotestosterone (DHT),
      and corticosterone (B) concentrations in both sexes and 17beta-estradiol (E2) and
      progesterone (P) in females only. We observed reproductive behaviors (e.g.,
      consortship, courtship, and copulation) in the field and measured testis and
      follicle size in male and female snakes from museum collections to relate steroid
      hormone concentrations to the timing of reproductive events. Our study revealed
      that C. oreganus in central California exhibits a bimodal pattern of breeding,
      with most mating behavior occurring in the spring and some incidences of mating
      behavior observed in late summer/fall. Each breeding period corresponded with
      elevated androgen (T or DHT) levels in males. Testes were regressed in the spring
      when the majority of reproductive behavior was observed in this population, and
      they reached peak volume in August and September during spermatogenesis. Although
      we did not detect seasonal variation in female hormone concentrations, some
      females had high E2 in the spring and fall, coincident with mating and with
      increased follicle size (indicating vitellogenesis) in museum specimens. Females
      with high E2 concentrations also had high T and DHT concentrations.
      Corticosterone concentrations in males and females were not related either to
      time of year or to concentrations of any other hormones quantified. Progesterone
      concentrations in females also did not vary seasonally, but this likely reflected
      sampling bias as females tended to be underground, and thus unobtainable, in
      summer months when P would be expected to be elevated during gestation. In
      females, P was positively correlated with T and DHT, and E2 was positively
      correlated with T.

PMID- 20138181
TI  - Mate calling behavior of male South African clawed frogs (Xenopus laevis) is
      suppressed by the antiandrogenic endocrine disrupting compound flutamide.
AB  - Several environmental pollutants have been identified as antiandrogenic endocrine
      disrupting chemicals (EDC), with flutamide (FLU) being a model compound for this
      type of action. Despite impacts of EDC interfering with sexual differentiation
      and reproduction in amphibians, established information about suggested effects
      on sexual behavior is still lacking. In this study adult male Xenopus laevis were
      injected with human chorionic gonadotropin (hCG) to initiate mate calling
      behavior. After one day hCG-stimulated frogs were treated via aqueous exposure
      over three days without and with FLU at concentrations of 10(-8) and 10(-6) M in
      comparison to untreated frogs. Androgen controlled mate calling behavior was
      recorded during the 12h dark period. At the end of exposure circulating levels of
      testosterone (T) and 17beta-estradiol (E2) were determined and furthermore gene
      expression was measured concerning reproductive biomarkers such as hypophysial
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), testicular
      aromatase (ARO), 5alpha reductase type 1 (SRD5alpha1) and 5alpha reductase type 2
      (SRD5alpha2). Both concentrations of FLU caused a significant decrease in calling
      activity starting at the second day of exposure. HCG injected positive controls
      had elevated levels of T compared to negative control frogs while in parallel
      treatment with FLU did not affect significantly the hCG elevated sex steroid
      levels. Furthermore, hCG treatment led to significantly decreased levels of gene
      expression for ARO and SRD5alpha2 but no impacts were detected on LH, FSH or
      SRD5alpha1 mRNA levels compared to negative controls. In summary, the behavioral
      parameter mate calling is the most sensitive biomarker detecting antiandrogenic
      modes of action in this challenge-experiment indicating that this non-invasive
      method could markedly contribute for sensitive assessment of antiandrogenic EDC.

PMID- 20138182
TI  - Identification of 7alpha-hydroxypregnenolone, a novel bioactive amphibian
      neurosteroid stimulating locomotor activity, and its physiological roles in the
      regulation of locomotion.
AB  - We now know that steroids can be synthesized de novo by the brain and the
      peripheral nervous system. Such steroids are called neurosteroids and de novo
      neurosteroidogenesis from cholesterol is a conserved property of vertebrate
      brains. Our studies over the past decade have demonstrated that the brain
      expresses several kinds of steroidogenic enzymes and produces a variety of
      neurosteroids in sub-mammalian species. However, neurosteroid biosynthetic
      pathways in amphibians, as well as other vertebrates may still not be fully
      mapped. We first found that the newt brain actively produces 7alpha
      hydroxypregnenolone, a previously undescribed amphibian neurosteroid. We then
      demonstrated that 7alpha-hydroxypregnenolone acts as a novel bioactive
      neurosteroid to stimulate locomotor activity of newt by means of the dopaminergic
      system. Subsequently, we analyzed the physiological roles of 7alpha
      hydroxypregnenolone in the regulation of locomotor activity of newt. This paper
      summarizes the advances made in our understanding of 7alpha-hydroxypregnenolone,
      a newly discovered bioactive amphibian neurosteroid stimulating locomotor
      activity, and its physiological roles in the regulation of locomotion in newt.

PMID- 20138183
TI  - Acute salinity challenges in Mozambique and Nile tilapia: differential responses
      of plasma prolactin, growth hormone and branchial expression of ion transporters.
AB  - The responses of Mozambique and Nile tilapia acclimated to fresh water (FW) and
      brackish water (BW; 17 per thousand) were compared following acute salinity
      challenges. In both species, plasma osmolality increased to above 450 mOsm by 2h
      after transfer from FW to seawater (SW); these increases in osmolality were
      accompanied by unexpected increases in plasma prolactin (PRL). Likewise, PRL
      receptor gene expression in the gill also increased in both species. In Nile
      tilapia, hyperosmotic transfers (FW to BW and SW) resulted in increased plasma
      growth hormone (GH) and in branchial GH receptor gene expression, responses that
      were absent in Mozambique tilapia. Branchial gene expression of osmotic stress
      transcription factor 1 (OSTF1) increased in both species following transfer from
      FW to SW, whereas transfer from BW to SW induced OSTF1 expression only in the
      Nile tilapia. Branchial expression of Na(+)/Cl(-) cotransporter was higher in FW
      in both species than in BW. Branchial gene expression of Na(+)/K(+)/2Cl(-)
      cotransporter (NKCC) increased after transfer from BW to SW in Mozambique
      tilapia, whereas expression was reduced in the Nile tilapia following the same
      transfer. The difference in the SW adaptability of these species may be related
      to a limited capacity of Nile tilapia to up-regulate NKCC gene expression, which
      is likely to be an essential component in the recruitment of SW-type chloride
      cells. The differential responses of GH and OSTF1 may also be associated with the
      disparate SW adaptability of these two tilapiine species.

PMID- 20138184
TI  - Expression of human FcgammaRIIIa as a GPI-linked molecule on CHO cells to enable
      measurement of human IgG binding.
AB  - The efficacy of a therapeutic IgG molecule may be as dependent on the
      optimisation of the constant region to suit its intended indication as on the
      selection of its variable regions. A crucial effector function to be maximised or
      minimised is antibody-dependent cell-mediated cytotoxicity by natural killer
      cells. Traditional assays of ADCC activity suffer from considerable inter-donor
      and intra-donor variability, which makes the measurement of antibody binding to
      human FcgammaRIIIa, the key receptor for ADCC, an attractive alternative method
      of assessment. Here, we describe the development of cell lines and assays for
      this purpose. The transmembrane receptor, FcgammaRIIIa, requires co-expression
      with signal transducing subunits to prevent its degradation, unlike the
      homologous receptor FcgammaRIIIb that is expressed as a GPI-anchored molecule.
      Therefore, to simplify the production of cell lines as reliable assay components,
      we expressed FcgammaRIIIa as a GPI-anchored molecule. Separate, stable CHO cell
      lines that express either the 158F or the higher-affinity 158V allotype of
      FcgammaRIIIa were isolated using fluorescence-activated cell sorting. The
      identities of the expressed receptors were confirmed using a panel of monoclonal
      antibodies that distinguish between subclasses and allotypes of FcgammaRIII and
      the cell lines were shown to have slightly higher levels of receptor than
      FcgammaRIII-positive peripheral blood mononuclear cells. Because the affinity of
      FcgammaRIIIa for IgG is intermediate amongst the receptors that bind IgG, we were
      able to use these cell lines to develop flow cytometric assays to measure the
      binding of both complexed and monomeric immunoglobulin. Thus, by choosing the
      appropriate method, weakly- or strongly-binding IgG can be efficiently compared.
      We have quantified the difference in the binding of wildtype IgG1 and IgG3
      molecules to the two functional allotypes of the receptor and report that the
      FcgammaRIIIa-158V-antibody interaction is 3- to 4-fold stronger that the
      interaction with FcgammaRIIIa-158F. Overall, these robust assays should be
      valuable for batch-testing clinical material as well as providing tools for
      improving the design of therapeutic IgG.

PMID- 20138185
TI  - Atrial stretch increases the gastric tonus of anesthetized rats.
AB  - AIMS: We assessed the effects of right atrial stretch on gastric tone and neuro
      humoral pathways involved in this phenomenon. MAIN METHODS: Anesthetized male
      rats were submitted for monitoring of the mean arterial pressure (MAP) and
      central venous pressure (CVP). A balloon catheter positioned into the stomach
      monitored by plethysmography the gastric volume (GV). All rats were monitored for
      55-min. After the first 20-min of monitoring (basal period), rats were either
      submitted to a 5-min interval of atrial stretch (AS) or maintained as controls.
      An intra-atrial balloon catheter was distended with 30, 50, or 70 microL of
      saline. GV and hemodynamic data were also monitored for a further 30-min. Another
      set of rats, either previously submitted to subdiaphragmatic vagotomy or
      splanchnicectomy plus celiac ganglionectomy or maintained as controls (sham),
      were also submitted to AS. Each subset consisted of six rats. The plasma level of
      the atrial natriuretic peptide (ANP) was measured in another group of rats. Data
      were compared by ANOVA followed by Bonferroni's test. KEY FINDINGS: In control
      rats, the GV, MAP, and CVP remained at stable levels throughout the studies. In
      addition to increase the CVP, AS also decreased (P<0.05) the GV by 14%, 11.5%,
      and 16.5% in the 30, 50, and 70 microL groups, respectively. Vagotomy prevented
      the GV decrease. In contrast, the AS decreased (P<0.05) the GV by 21.3% in
      splanchnicectomized rats. SIGNIFICANCE: AS decreased the GV of rats in a volume
      dependent manner, a phenomenon prevented by vagotomy but enhanced by celiac
      ganglionectomy.

PMID- 20138186
TI  - Immunodominance analysis through interactions of CD8+ T cells and DCs in lymph
      nodes.
AB  - Immunodominance is a common phenomenon observed in multiple epitopes immune
      systems. Previous studies hypothesize that the competition among CD8+ T cell
      responses against different epitopes can be used to explain immunodominance. This
      paper proposes a mathematical model that describes the dynamics of CD8+ T cells
      primed by antigen-presenting dendritic cells (DCs) in the lymph nodes, and shows
      that the overall avidity of the interactions between peptide-specific T cells and
      cognate antigen-bearing DCs may determine the immunodominance. The model suggests
      the probability that a peptide-specific T cell be immunodominant is proportional
      to (1) the cognate T cell receptor (TCR) affinity, (2) the number of complexes of
      cognate peptide and major histocompatibility complex (pMHC) per DC, and (3) the
      half-life of cognate peptide-specific pMHC. The model predicts a threshold
      density of pMHC complexes for T cell activation. These observations from the
      mathematical model are consistent with experimental studies in the open
      literature. For DC-based vaccine design, the model suggests a strategy of
      immunotherapy based on the injection of cognate antigen-pulsed DCs.

PMID- 20138187
TI  - Ontogeny of ethanol-induced motor impairment following acute ethanol: assessment
      via the negative geotaxis reflex in adolescent and adult rats.
AB  - Adolescent rats have been observed to be less sensitive than adults to a number
      of ethanol effects that may serve as feedback cues to reduce further ethanol
      intake. Among these findings are a few reports of attenuated sensitivities of
      adolescents to ethanol-induced motor impairment. The purpose of the present study
      was to further explore potential age-related differences in ethanol-induced motor
      impairment in both male and female adolescent (postnatal day [P]28-32), and adult
      (P68-72) Sprague-Dawley rats using an inclined plane assessment of the negative
      geotaxis reflex. Adult males displayed significant motor impairment at 1.5 g/kg,
      whereas adolescent males required higher doses, showing significant motor
      impairment only at doses of 2.25 g/kg ethanol or greater. Intoxicated practice
      did not significantly influence level of motor impairment at either age. When
      female rats of both ages were separately analyzed in terms of their response to
      ethanol, a dose of 1.5 g/kg ethanol was found to significantly impair adults,
      whereas adolescent females showed significant motor impairment when challenged
      with 2.25 g/kg but not 1.5 g/kg ethanol. Yet when the 1.5 g/kg data of females at
      the two ages were directly compared, no significant age difference was seen at
      this dose. These data document an attenuated sensitivity of adolescent relative
      to adult rats to the motor impairing effects of ethanol using a stationary
      inclined plane test, an effect particularly robust in male animals, and
      demonstrates the utility of this test for assessment of motor coordination in
      adolescent and adult rats.

PMID- 20138188
TI  - 2009 H1N1 influenza infection in cancer patients and hematopoietic stem cell
      transplant recipients.
AB  - OBJECTIVES: Although usually mild, 2009 H1N1 Influenza has caused up to 6000
      deaths in the US. To determine outcome in patients with cancer and/or
      hematopoietic stem cell transplant (HSCT), we reviewed our recent experience at
      Memorial Sloan-Kettering Cancer Center (MSKCC). METHODS: During the initial NYC
      outbreak (May 19-June 30, 2009), all respiratory samples at MSKCC were tested for
      2009 H1N1 influenza by DFA, culture, and RT-PCR. Medical records were reviewed
      for all cases. RESULTS: During the 6-week period, 45(11%) of 394 tested patients
      were diagnosed with 2009 H1N1 Influenza. These included 29(17%) of 167 patients
      with hematologic conditions compared to 16(7%) of 226 with solid tumors (P <
      0.01). 21(22%) of 96 tested HSCT recipients were positive. Cough (93%) and fever
      (91%) were common. Of 29 patients who were radiographically assessed, 8(27%) had
      lower airway disease. 17(37%) were hospitalized. None required mechanical
      ventilation. No deaths were attributed to influenza. All treated patients
      tolerated antiviral medication. CONCLUSIONS: 2009 H1N1 Influenza caused mild
      symptoms in most patients with cancer and/or HSCT. None died or required
      mechanical ventilation. Immunosuppression from cancer or its treatment including
      HSCT may not be a substantial risk for poor outcome, however further studies are
      needed to validate our results.

PMID- 20138189
TI  - Effect of GM-CSF in combination with hepatitis B vaccine on revacination of
      healthy adult non-responders.
AB  - OBJECTIVE: To assess the immune effects and safety of using GM-CSF with the yeast
      recombinant hepatitis B virus (HBV) vaccine for the re-vaccination of healthy
      adults who did not respond to a previous vaccination. METHODS: Study participants
      included 1784 healthy adults and 100 individuals diagnosed as non-responders.
      These healthy non-responders were randomly assigned to one of the three treatment
      groups: Group A (34 individuals) was given 150 microg of granulocyte-macrophage
      colony stimulating factor (GM-CSF) the first day, then 20 microg of the vaccine;
      Group B (33 individuals) was given 40 microg of the vaccine only; and, group C
      (33 individuals) was injected with 20 microg of vaccine each time. All
      participants were injected three times, at time of study enrollment and one and
      six months later. Anti-HB surface antigen (HBs) antibody titers were tested
      before treatment and at one (T1), two (T2) and eight (T8) months post-first
      injection. RESULTS: At T1, the rate of anti-HBs antibody(+) in groups A, B and C
      was 26.47%, 48.48% and 18.18%, respectively (p = .027). At T8, the seropositive
      rate of group A (64.71%) and group B (75.76%) was significantly higher than in
      group C (39.39%) (p = .011); the geometric mean of the antibody titer for groups
      A and B was higher than for group C (p = .0173). All three treatments were safe
      and well-tolerated. CONCLUSIONS: Augmentation of the vaccine dose and co
      administration of GM-CSF and the standard vaccine dose are effective for HBV
      vaccine non-responders. In fact, changing the vaccine dose had a better
      seropositive response than injecting the vaccine in combination with GM-CSF.

PMID- 20138190
TI  - Atypical behavioural effects of lorazepam: clues to the design of novel
      therapies?
AB  - Aside from their pharmacokinetic properties, e.g. their speed of action and the
      duration of residual effects, benzodiazepines are still considered as equivalent
      in terms of their effects on cognition. Here we review evidence suggesting that
      certain benzodiazepines, especially lorazepam, differ in a number of respects, in
      particular with respect to their effects on cognition. We focus this review on
      memory, attention and visual perception, where impairments may be brought about
      by only a subset of benzodiazepines in spite of their administration at doses
      inducing similar sedative effects. This precludes an explanation in terms of
      sedation. Differences in the effects of benzodiazepines have also been found in
      electrophysiological and animal behavioural studies. These studies are important
      for therapeutic approaches for two reasons: first, effects of benzodiazepine
      prescription on cognitive functions will differ according to the benzodiazepine,
      contrary to what is usually believed. Less straightforwardly are the possible
      therapeutic implications of specific effects on cognition following treatment
      with lorazepam. Indeed, the specific effects this drug has on cognition may
      reveal not only side-effects but also effects of potential therapeutic value.
      Current research concentrates on a fine scale analysis of the effects of GABA on
      different sub-types of GABA(A) receptors. We suggest that from looking at what
      makes lorazepam different in a behavioural sense from other benzodiazepines we
      may be in a position to design innovative treatments for major aspects of complex
      disorders, including schizophrenia.

PMID- 20138191
TI  - Emerging new technologies in Pharmacogenomics: rapid SNP detection, molecular
      dynamic simulation, and QSAR analysis methods to validate clinically important
      genetic variants of human ABC Transporter ABCB1 (P-gp/MDR1).
AB  - Pharmacogenomics, the study of the influence of genetic factors on drug action,
      is increasingly important for predicting pharmacokinetics profiles and/or adverse
      reactions to drugs. Drug transporters as well as drug-metabolism play pivotal
      roles in determining the pharmacokinetic profiles of drugs and, by extension,
      their overall pharmacological effects. There are an increasing number of reports
      addressing genetic polymorphisms of drug transporters. A key requirement for the
      development of individualized medicine or personalized therapy is the ability to
      rapidly and conveniently test patients for genetic polymorphisms and/or
      mutations. We have recently developed a rapid and cost-effective method for
      single nucleotide polymorphism (SNP) detection, named Smart Amplification Process
      2 (SmartAmp2), which enables us to detect genetic polymorphisms or mutations in
      30 to 45min under isothermal conditions without DNA isolation and PCR
      amplification. Furthermore, high-speed functional screening, quantitative
      structure-activity relationship (QSAR) analysis, and molecular dynamic (MD)
      simulation methods have been developed to study the substrate specificity of ABC
      transporters and to evaluate the effect of genetic polymorphisms on their
      function and substrate specificity. These methods would provide powerful and
      practical tools for screening synthetic and natural compounds, and the deduced
      data can be applied to the molecular design of new drugs. This review addresses
      such new methods for validating genetic polymorphisms of human ABC transporter
      ABCB1 (P-gp/MDR1) which is critically involved in the pharmacokinetics of drugs.

PMID- 20138192
TI  - Secretoneurin and the tachykinins substance P and neurokinin-A/B in NMDA-induced
      excitotoxicity in the rat retina.
AB  - In a recent investigation using the NMDA-excitotoxicity model in the rat retina,
      we found that, whereas, following intravitreal injection of NMDA, a time
      dependent decrease of the levels of a neuropeptide, namely vasoactive intestinal
      polypeptide (VIP), was fully counteracted by topical treatment with flunarizine
      eye drops, the levels of pituitary adenylate-cyclase activating peptide-38 (PACAP
      38), another neuropeptide, remained unchanged. The aim of the present study was
      to find out if NMDA causes reduction in the levels of other neuropeptides such as
      secretoneurin (SN), neurokinin-A/B (NKA/NKB) and substance P (SP), and if so,
      whether flunarizine has the ability to counteract this effect or prevent such
      reduction. The reduction of the levels of SN and NKA/NKB 14 days after
      intravitreal injection of 2 MUl of 100 nmol NMDA into one eye was more pronounced
      than after 7 days; topical flunarizine had a slight counteracting effect, but
      could not prevent the decrease in the levels of these peptides. Reduction in SP
      levels after 28 and 56 days was fully counteracted by flunarizine. By enabling a
      pronounced influx of Ca2+ ions into peptide-expressing cells, NMDA leads to cell
      death. Since each of these peptides exerts neuroprotective properties in the
      central nervous system, the drop in their levels caused by acute insult (e.g.
      NMDA excitotoxicity) or chronic insult (e.g. glaucoma) may cause a breakdown of
      endogenous neuroprotection in the retina given that these peptides feature
      neuroprotective properties in the retina as well.

PMID- 20138193
TI  - Cytosolic phospholipase A(2)-alpha enhances induction of endoplasmic reticulum
      stress.
AB  - Induction of endoplasmic reticulum (ER) stress by the complement membrane attack
      complex is enhanced by activation of cytosolic phospholipase A(2)-alpha
      (cPLA(2)). To address mechanisms by which cPLA(2) may modulate ER stress, we
      produced a mutant cPLA(2), containing an ER targeting domain (cPLA(2)-ERmut).
      After transfection and fractionation of COS-1 cells, cPLA(2)-ERmut was present
      mainly in the membrane fraction, whereas wild type (wt) cPLA(2) was principally
      in the cytosol. By fluorescence microscopy, cPLA(2)-ERmut was enriched in a
      perinuclear distribution under basal conditions, colocalizing with the ER
      protein, calnexin, while cPLA(2)-wt was mainly cytosolic. Both forms of cPLA(2)
      transiently expressed in COS cells showed basal phosphorylation at serine(505),
      which correlates with catalytic activity. Expression of cPLA(2)-wt was
      approximately 5-fold greater, compared with cPLA(2)-ERmut, but both enzymes
      produced comparable increases in free arachidonic acid, implying that cPLA(2)
      ERmut effectively hydrolyzed ER membrane phospholipids. Although transfection of
      cPLA(2)-ERmut or wt did not induce ER stress independently, cPLA(2)-ERmut and wt
      enhanced the induction of ER stress by tunicamycin, dithiothreitol and ionomycin
      (monitored by induction of grp94 and C/EBP homologous protein-10), and the effect
      was dependent on the catalytic activity. cPLA(2)-ERmut enhanced production of
      superoxide. Induction of ER stress in tunicamycin-treated cells expressing
      cPLA(2)-ERmut was attenuated in the presence of the antioxidant, N-acetyl
      cysteine, and reduced glutathione, and was exacerbated by dl-buthionine-(S,R)
      sulfoximine (which depletes glutathione). Expression of cPLA(2)-ERmut exacerbated
      tunicamycin-induced apoptosis. Thus, induction of ER stress is facilitated by the
      activation of cPLA(2) at the ER. The mechanism involves ER membrane phospholipid
      hydrolysis, and accumulation of reactive oxygen species.

PMID- 20138194
TI  - Sample storage for soil enzyme activity and bacterial community profiles.
AB  - Storage of samples is often an unavoidable step in environmental data collection,
      since available analytical capacity seldom permits immediate processing of large
      sample sets needed for representative data. In microbiological soil studies,
      sample pretreatments may have a strong influence on measurement results, and thus
      careful consideration is required in the selection of storage conditions. The aim
      of this study was to investigate the suitability of prolonged (up to 16 weeks)
      frozen or air-dried storage for divergent soil materials. The samples selected to
      this study were mineral soil (clay loam) from an agricultural field, humus from a
      pine forest and compost from a municipal sewage sludge composting field. The
      measured microbiological parameters included functional profiling with ten
      different hydrolysing enzyme activities determined by artificial fluorogenic
      substrates, and structural profiling with bacterial 16S rDNA community
      fingerprints by amplicon length heterogeneity analysis (LH-PCR). Storage of
      samples affected the observed fluorescence intensity of the enzyme assay's
      fluorophor standards dissolved in soil suspension. The impact was highly
      dependent on the soil matrix and storage method, making it important to use
      separate standardisation for each combination of matrix type, storage method and
      time. Freezing proved to be a better storage method than air-drying for all the
      matrices and enzyme activities studied. The effect of freezing on the enzyme
      activities was small (<20%) in clay loam and forest humus and moderate (generally
      20-30%) in compost. The most dramatic decreases (>50%) in activity were observed
      in compost after air-drying. The bacterial LH-PCR community fingerprints were
      unaffected by frozen storage in all matrices. The effect of storage treatments
      was tested using a new statistical method based on showing similarity rather than
      difference of results.

PMID- 20138195
TI  - Detection by whole genome microarrays of a spontaneous 126-gene deletion during
      construction of a ytfE mutant: confirmation that a ytfE mutation results in loss
      of repair of iron-sulfur centres in proteins damaged by oxidative or nitrosative
      stress.
AB  - We show that genomic hybridization allows detection of a spontaneous secondary
      deletion of 126 genes that occurred during construction of an Escherichia coli
      ytfE mutant, LMS4209, explaining some of its unexpected growth defects. We
      confirm that YtfE is required to repair damage to iron-sulfur centres and for
      hydrogen peroxide resistance.

PMID- 20138196
TI  - Structural and pharmacological characteristics of chimeric peptides derived from
      peptide E and beta-endorphin reveal the crucial role of the C-terminal YGGFL and
      YKKGE motifs in their analgesic properties.
AB  - Peptide E (a 25-amino acid peptide derived from proenkephalin A) and beta
      endorphin (a 31-amino acid peptide derived from proopiomelanocortin) bind with
      high affinity to opioid receptors and share structural similarities but induce
      analgesic effects of very different intensity. Indeed, whereas they possess the
      same N-terminus Met-enkephalin message sequence linked to a helix by a flexible
      spacer and a C-terminal part in random coil conformation, in contrast with
      peptide E, beta-endorphin produces a profound analgesia. To determine the key
      structural elements explaining this very divergent opioid activity, we have
      compared the structural and pharmacological characteristics of several chimeric
      peptides derived from peptide E and beta-endorphin. Structures were obtained
      under the same experimental conditions using circular dichroism, computational
      estimation of helical content and/or nuclear magnetic resonance spectroscopy
      (NMR) and NMR-restrained molecular modeling. The hot-plate and writhing tests
      were used in mice to evaluate the antinociceptive effects of the peptides. Our
      results indicate that neither the length nor the physicochemical profile of the
      spacer plays a fundamental role in analgesia. On the other hand, while the
      functional importance of the helix cannot be excluded, the last 5 residues in the
      C-terminal part seem to be crucial for the expression or absence of the analgesic
      activity of these peptides. These data raise the question of the true function of
      peptides E in opioidergic systems.

PMID- 20138197
TI  - CD8(+)Foxp3(+) T cells in peripheral blood of relapsing-remitting multiple
      sclerosis patients.
AB  - A defect of CD4(+) regulatory T cells (Treg) seems to be involved in the
      pathogenesis of multiple sclerosis (MS). Besides Treg, CD8(+) T cells also can
      suppress the immune response. Forkhead box p3 (Foxp3) is known to program the
      acquisition of suppressive capacities in CD4(+) T cells and recent studies showed
      that in vitro antigen activation leads to Foxp3 expression in CD8(+) T cells,
      gaining of suppressive activity. By flow cytometry we found a lower percentage of
      circulating CD8(+)Foxp3(+) T cells in relapsing than in remitting patients with
      MS and in controls. No significant differences were observed in CD8(+)Foxp3(+) T
      cell percentage between healthy subjects and patients in remission. Our data
      suggest that peripheral CD8(+)Foxp3(+) T cells may play a role in the maintenance
      of tolerance in MS.

PMID- 20138198
TI  - Association of a trait-like bias towards the perception of negative subjective
      life events with risk of developing premenstrual symptoms.
AB  - OBJECTIVE: Premenstrual symptoms affect the majority of healthy women.
      Premenstrual symptomatology has earlier been linked to stress and a state-like
      alteration in the perception of life events in the late-luteal phase of the
      menstrual cycle. We hypothesised that there is also a trait-like negative bias in
      the perception of life events evident throughout the whole cycle which is
      associated with the likelihood to manifest more marked symptoms in the late
      luteal phase of the cycle. METHODS: 88 healthy women completed the PRISM calendar
      for three consecutive cycles and the Objective and Subjective Event Checklist
      during the follicular phase of the first cycle. Association between PRISM score
      change from the follicular through the late-luteal phase and life event variables
      was investigated by Generalized Linear Model Analysis (GENMOD). RESULTS: The
      PRISM score change showed a significant negative association with the ratio of
      positive subjective life events and a significant positive association with the
      ratio of negative subjective life events. There were no significant results in
      case of the objective life events. CONCLUSION: Our results indicate that women
      manifesting a more marked increase of symptoms from the late follicular through
      the late-luteal phase of the menstrual cycle are more likely to notice negative
      subjective life events and less likely to notice positive subjective life events.
      This suggest a trait-like negative bias in the perception of life events present
      throughout the whole reproductive cycle which may play an important role in the
      emergence of premenstrual symptoms.

PMID- 20138199
TI  - Mirtazapine treatment of periodic catatonia in organic mental disorder: a case
      report.

PMID- 20138200
TI  - Escitalopram induced galactorrhoea: a case report.

PMID- 20138201
TI  - Repeated filicide-suicide attempts by a mother with bipolar II depression.

PMID- 20138202
TI  - Vitamin E modulates reproductive toxicity of pyrethroid lambda-cyhalothrin in
      male rabbits.
AB  - The objective of the current study was to analyze the reproductive toxicity
      caused by lambda-cyhalothrin (LCT) in male rabbits, and to evaluate the possible
      protective effect of vitamin E (Vit. E) as antioxidant. Animals were orally
      administered their respective doses of LCT every other day and given drinking
      water supplemented with vitamin E for 16 weeks. Results showed that semen quality
      was deteriorated following treatment with LCT. Also, testosterone levels, body
      weight (BW), feed intake (FI), and relative testes (RTW) and epididymis (REW)
      weights were significantly decreased. Concentrations of thiobarbituric acid
      reactive substances (TBARS) were significantly increased in seminal plasma of
      rabbits treated with LCT compared with control. While, activities of glutathione
      S-transferase (GST), transaminases and acid phosphatase (AcP) were significantly
      decreased. Vitamin E alone significantly increased testosterone levels, BW, FI,
      RTW, REW, semen characteristics and seminal plasma enzymes, and decreased the
      levels of TBARS. Also, the present study showed that vitamin E might be effective
      against LCT-induced reproductive toxicity. It was suggested that LCT exerted a
      significant adverse effect on reproductive performance of male rabbits.
      Furthermore, vitamin E antagonized the toxic effects of LCT and improved semen
      quality of male rabbit.

PMID- 20138203
TI  - Establishment of a methodology for investigating protectants against ethanol
      induced hepatotoxicity.
AB  - Ethanol-induced liver injury has been extensively reported in clinic, but still
      lacks an efficient in vitro platform for investigating its hepatotoxicity and
      protectants. This study aimed to establish a methodology on the culture
      conditions regarding the sealability against evaporation of ethanol, culture
      medium and 2D/3D culture of hepatocytes. Based on the experimental findings, it
      was indicated that the ethanol evaporation from culture plates was a severe
      problem reducing its toxicity in hepatocyte. According to the detected ethanol
      toxic response marked by reduced cell viability, 3D cultured hepatocytes in gel
      entrapment were suggested to be better than 2D hepatocyte in monolayer, but the
      cultures in either William's Medium E or DMEM exhibited comparable sensitivity to
      ethanol toxicity. Subsequently, 3D cultured hepatocytes with Parafilm sealing
      were systematically illustrated to well reflect the ethanol-induced lipid
      accumulation, reactive oxygen species/malondialdehyde generation, glutathione
      depletion and cytochrome 2E1 induction. Finally, such hepatocyte models were
      proposed as a platform for screening of herbal component against ethanol
      hepatotoxicity. Nano-silibinin, for the first time, found to perform significant
      protection against ethanol-induced hepatotoxicity while silibinin in normal
      particles could not inhibit such toxicity. This protection of nano-silibinin
      might relate to its improved bioavailability compared to normal insoluble
      silibinin and could act as an anti-oxidative and anti-steatosis agent against
      ethanol-induced hepatotoxicity.

PMID- 20138204
TI  - Acute toxicity of berberine and its correlation with the blood concentration in
      mice.
AB  - The aim of this study was to investigate the LD(50) (median lethal dosage) of
      berberine (BBR) through three different routes of injection in mice: intravenous
      (i.v.) injection, intraperitoneal (i.p.) injection, and intragastric (i.g.) oral
      administration. The concentration of BBR in blood from their i.g. doses (10.4,
      20.8, 41.6, and 83.2 g/kg) and the content relationship of BBR among different
      injections were analyzed by high-performance liquid chromatography (HPLC). The
      LD(50) of BBR from i.v. and i.p. injections is 9.0386 and 57.6103 mg/kg,
      respectively; but no LD(50) was found in the i.g. group. A significant difference
      in bioavailability was observed between the different routes. Furthermore, the
      concentration of BBR in the blood from different i.g. doses was also
      significantly different. However, we discovered an interesting phenomenon
      indicating that the absorption of BBR by oral administration has a limit,
      therefore, explaining the difficulty in obtaining an LD(50) of BBR for i.g.
      injection. From the analysis of BBR content in blood after various
      administrations, we hypothesized that not only does the concentration of BBR in
      blood contribute to its acute toxicity, but also the routes of administration may
      be an important facet that affects this toxicity evaluation.

PMID- 20138205
TI  - Biochemical and structural properties of gamma-glutamyl transpeptidase from
      Geobacillus thermodenitrificans: an enzyme specialized in hydrolase activity.
AB  - Gamma-glutamyltranspeptidases (gamma-GTs) catalyze the transfer of the gamma
      glutamyl moiety of glutathione and related gamma-glutamyl amides to water
      (hydrolysis) or to amino acids and peptides (transpeptidation) and play a key
      role in glutathione metabolism. Recently, gamma-GTs have been considered
      attractive pharmaceutical targets for cancer and useful tools to produce gamma
      glutamyl compounds. To find out gamma-GTs with special properties we have chosen
      microorganisms belonging to Geobacillus species which are source of several
      thermostable enzymes of potential interest for biotechnology. gamma-GT from
      Geobacillus thermodenitrificans (GthGT) was cloned, expressed in Escherichia
      coli, purified to homogeneity and characterized. The enzyme, synthesized as a
      precursor homotetrameric protein of 61-kDa per subunit, undergoes an internal
      post-translational cleavage of the 61 kDa monomer into 40- and 21-kDa shorter
      subunits, which are then assembled into an active heterotetramer composed of two
      40- and two 21-kDa subunits. The kinetic characterization of the hydrolysis
      reaction using L-glutamic acid gamma-(4-nitroanilide) as the substrate reveals
      that the active enzyme has K(m) 7.6 microM and V(max) 0.36 micromol min/mg. The
      optimum pH and temperature for the hydrolysis activity are 7.8 and 52 degrees C,
      respectively. GthGT hydrolyses the physiological antioxidant glutathione,
      suggesting an involvement of the enzyme in the cellular defense mechanism against
      oxidative stress. Unlike other gamma-GTs, the mutation of the highly conserved
      catalytic nucleophile, Thr353, abolishes the post-translational cleavage of the
      pro-enzyme, but does not completely block the hydrolytic action. Furthermore,
      GthGT does not show any transpeptidase activity, suggesting that the enzyme is a
      specialized gamma-glutamyl hydrolase. The GthGT homology-model structure reveals
      peculiar structural features, which should be responsible for the different
      functional properties of the enzyme and suggests the structural bases of protein
      thermostability.

PMID- 20138206
TI  - Aging diurnal rhythms and chronic stress: Distinct alteration of diurnal
      rhythmicity of salivary alpha-amylase and cortisol.
AB  - The present study assessed diurnal profiles of salivary alpha-amylase (sAA),
      proposed as a marker of autonomic activity, and salivary cortisol in competitive
      ballroom dancers as well as age- and sex-matched controls to investigate age
      related changes of basal activity and potential chronic psychosocial stress
      related alterations. According to the Allostatic Load (AL) hypothesis of a
      cumulative wear and tear of the body we expected to see physiological
      accumulation of the effects of stress and age especially pronounced in older
      dancers. Dancers and controls collected five saliva samples throughout the day.
      Daily overall output of sAA was elevated in older adults while there was no
      effect of age on mean cortisol levels. Alterations of diurnal rhythms were only
      seen in younger male dancers showing a flattened diurnal profile of sAA and
      younger dancers and female older dancers showing a blunted diurnal rhythmicity of
      cortisol. Furthermore, we found a negative correlation between summary indices of
      basal sAA and the amount of physical activity. In conclusion, higher overall
      output of sAA in older adults is in line with the phenomenon of a sympathetic
      "drive" with increasing age. Furthermore, a lower output of sAA in people who are
      more physical active is in line with the hypothesis of an exercise-induced
      decrease of sympathetic activity. Overall, our study does not support the AL
      hypothesis, but rather highlights the importance of regular physical activity and
      social environment in promoting health.

PMID- 20138207
TI  - Analysis of relative gene dosage and expression differences of the paralogs
      RABL2A and RABL2B by Pyrosequencing.
AB  - The paralogous genes RABL2A (chr2) and RABL2B (chr22) emerged by duplication of a
      single gene in the human-chimpanzee ancestor and share a high degree of sequence
      similarity. In Phelan-McDermid-Syndrome microdeletions of 22q13 often also
      affecting RABL2B are of clinical importance but their incidence is still unknown.
      We analyzed a German population (190 individuals) for such aneuploidies and the
      paralogs' expression in cell lines by RABL2 paralogous sequence quantification.
      For determination of the genomic and transcriptional ratios of RABL2A and RABL2B
      a Pyrosequencing protocol was introduced as a high-throughput method. During PCR
      the 3' end of the biotinylated strand is engineered by a backfolding
      oligonucleotide to hybridize in the Pyrosequencing reaction to an internal site
      near the sequence to be analyzed. In human samples no deviations of the euploid
      genomic state could be detected indicating that 22q13 microdeletions involving
      RABL2B are rare. However, despite equal gene dosage a preferential expression of
      RABL2B in human tissues and lymphoblastoid cell lines was detected which is most
      pronounced in brain and placenta. This renders a complete functional
      complementation of one paralog by the respective other unlikely and hints to a
      functional and clinical importance, in particular with respect to the 22q13
      chromosomal deletion syndrome. Remarkably and in contrast to human, expression
      levels of the two paralogs in a chimpanzee cell line are equal. This finding is
      discussed in view of the relocation of RABL2A from its ancestral telomeric to its
      pericentromeric location in human.

PMID- 20138208
TI  - Pharmacological and toxicological effects of Paronychia argentea in experimental
      calcium oxalate nephrolithiasis in rats.
AB  - AIM OF THE STUDY: Renal protection and antiurolithiasic effects of two extracts
      of Paronychia argentea (PA), a traditional Algerian plant commonly known as
      Algerian tea, were evaluated. This study was carried out to determine whether the
      aqueous extract (APA) or the butanolic extract (BPA) of aerial parts could
      prevent or reduce calculi aggregation in experimental calcium oxalate (Ox)
      nephrolithiasis in Wistar rats. MATERIALS AND METHODS: The two extracts (APA and
      BPA) were administrated orally and daily, during 28 days to nephrolithiasic
      treated rats at the dose of 250, 500 mg/kg b.w. and 10, 20mg/kg b.w.
      respectively. Body weight, renal index, liver index, serum level of creatinine,
      uric acid, urea, K(+), Ca(2+), Mg(2+), Na(+) and transaminase (alanine
      aminotransferase, ALT; aspartate aminotransferase, AST), phosphatase alkaline
      activity (PAL) were evaluated following the 28 days treatment in rats. In
      addition histopathological changes in kidney and liver were stained in
      hematoxylin eosin (HE). RESULTS: The effect of the extracts could be advantageous
      in preventing urinary stone retention by reducing renal necrosis and thus inhibit
      crystal retention. In contradiction with APA, the two doses of BPA attenuated
      elevation in the serum creatinine (p<0.01) and blood urea levels (p<0.01)
      (nephroprotective effect). However, the increase in ALT (27%) and PAL (31-51%)
      serum levels and in the relative liver weights (p<0.01) in the groups treated
      with doses of APA may indicate that this extract has not a hepatoprotective
      effect against oxalate toxicity. CONCLUSIONS: The presented data indicate that
      administration of the butanolic extract of aerial parts to rats with NaOx induced
      lithiasis, and reduced and prevented the growth of urinary stones in experimental
      calcium oxalate nephrolithiasis in Wistar rats.

PMID- 20138209
TI  - The effects of the Chinese herbal medicine EMF01 on salicylate-induced tinnitus
      in rats.
AB  - AIM OF THE STUDY: Traditional Chinese medicine (TCM) has been reported to
      successfully alleviate tinnitus, although well-controlled studies have not been
      conducted. In this study, we attempted to test a TCM, Er Ming Fang (EMF01)
      containing Rehmannia glutinosa, Cornus officinalis, Salvia mittiorrhiza,
      Pueraria, Schisandra chinensis, Poria cocos and Platycodon grandiflorum, on
      salicylate-induced tinnitus in rats, using a conditioned lick suppression
      paradigm. MATERIALS AND METHODS: A pilot study examined the effect of 8.75 g/kg
      and 17.5 g/kg EMF01 (delivered by oral gavage for 20 days) and showed a slight
      decrease in the suppression ratio (SR) in the 8.75 g/kg group. In order to
      confirm the possible effect of EMF01 on tinnitus at 8.75 g/kg, a further study
      was carried out with a larger sample size. RESULTS: While there were
      statistically significant differences between the treatment groups, post hoc
      tests revealed that EMF01 did not have any significant effect on salicylate
      induced tinnitus. CONCLUSIONS: While this study does not support the efficacy of
      EMF01 in the treatment of salicylate-induced tinnitus, further studies should be
      conducted to determine if it alleviates tinnitus associated with acoustic trauma.

PMID- 20138210
TI  - Ethnopharmacological application of medicinal plants to cure skin diseases and in
      folk cosmetics among the tribal communities of North-West Frontier Province,
      Pakistan.
AB  - AIM OF THE STUDY: The present investigation is an attempt to find out
      ethnopharmacological application of medicinal plants to cure skin diseases and in
      folk cosmetics. METHOD: We interviewed respondents in 30 remote sites of North
      West Frontier Province by a structured interview form in the local language and
      respondents were queried for the type of herbal cure known to him. RESULTS: A
      total of 66 plant species belonging to 45 families have been recorded. Seventy
      five medications for 15 skin diseases and cosmetics were documented. The mode of
      application was topical as well as oral administration. Water, milk, ghee, oil,
      eggs, sulphur and butter are used during administration of herbal remedies. About
      15 plant species are known for their use to cure multiple skin diseases. Among
      these Berberis lyceum, Bergenia ciliata, Melia azedarach, Otostegia limbata,
      Phyla nodiflora, Prunus persica and Zingiber officinale constitutes major plants.
      The herbal cosmetics products range from face freshness, removal of ugly spots,
      hair care, and colouring of palm, feet, gums, and teeth. CONCLUSION: Most of the
      reported species are wild and rare; this demands an urgent attention to conserve
      such vital resources so as to optimize their use in the primary health care
      system. Since most of the skin diseases are caused by bacteria, viruses and fungi
      in this context, phytochemical screening for active constituents, biological
      activities and clinical studies is of global importance.

PMID- 20138211
TI  - 10-Hydroxy-2-decenoic acid from Royal jelly: a potential medicine for RA.
AB  - AIM OF THE STUDY: Rheumatoid arthritis synovial fibroblasts (RASFs) are known to
      produce matrix metalloproteinases (MMPs) and cause joint destruction. The purpose
      of this study is to develop a potential medicine for rheumatoid arthritis (RA).
      MATERIALS AND METHODS: To this end, first, the MMPs inhibition factor was
      purified from an alkali-solubilized fraction of RJ (Apis mellifera) by C18
      reverse-phase column chromatography and identified as 10-hydroxy-2-decenoic acid
      (10H2DA) by LTQ XL analysis. Next, Experimental test 10H2DA how to inhibited the
      activities of MMPs: with RASFs isolated from rheumatoid tissues by enzymatic
      digestion, cultures in monolayers were treated with 10H2DA (0.5mM, 1mM, and 2mM)
      or PBS for 2h followed by stimulation with TNF-alpha (10 ng/ml) for 2h, mRNA.
      Protein levels of MMP-1 and MMP-3 were measured by real-time PCR and enzyme
      linked immunosorbent assay (ELISA), the DNA-binding activity of activator protein
      1 (AP-1) and nuclear factor kappaB (NF-kappaB) by electrophoretic mobility shift
      assay (EMSA), and the protein kinase activity of p38, ERK and JNK by kinase
      assay. RESULTS: The molecular investigation revealed that the 10H2DA-mediated
      suppression was likely to occur through blocking p38 kinase and c-Jun N-terminal
      kinase-AP-1 signaling pathways. In contrast, 10H2DA had no effect on
      extracellular signal-regulated kinase activity, NF-kappaB DNA-binding activity
      and IkappaBalpha degradation. CONCLUSION: These results suggest that 10H2DA may
      be of potential therapeutic value in inhibiting joint destruction in RA.

PMID- 20138212
TI  - Zinc induces depletion and aggregation of endogenous TDP-43.
AB  - Ubiquitinated neuronal aggregates containing TDP-43 are pathological hallmarks in
      the spectrum of frontotemporal lobar dementia (FTLD) and amyotrophic lateral
      sclerosis (ALS). In affected neurons, TDP-43 undergoes C-terminal fragmentation,
      phosphorylation, and ubiquitination and forms aggregates in the cytoplasm or
      nucleus. Although in vitro studies have been able to recapitulate these features
      using transfected cell culture models, little is known about the biochemical
      mechanisms that underlie pathological changes to endogenous TDP-43. As altered
      metal ion homeostasis and increased oxidative stress are central features of
      neurodegeneration, including FTLD and ALS, we sought to determine the affects of
      these factors on endogenous TDP-43 metabolism in mammalian cells. Treatment of
      SY5Y neuronal-like cells expressing endogenous TDP-43 with zinc (Zn) induced
      depletion of TDP-43 expression and formation of inclusions that were TDP-43
      positive. TDP-43 was also detected in the cytosol of Zn-affected cells but this
      was not aggregated. No evidence of C-terminal fragmentation, phosphorylation, or
      ubiquitination was observed. The depletion and aggregation of TDP-43 were
      associated with the specific action of Zn but were not seen with copper, iron, or
      H(2)O(2). These studies describe for the first time specific induction of
      endogenous TDP-43 aggregation in neuronal-like cells and suggest that specific Zn
      associated processes could affect TDP-43 metabolism in neurodegenerative
      diseases.

PMID- 20138213
TI  - Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human
      inflammatory bowel disease whole-blood model.
AB  - Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent
      intake of anti-inflammatory and/or immunosuppressive drugs, leading to
      significant adverse events. To evaluate the role solid lipid nanoparticles (SLN)
      play as drug delivery system in enhancing anti-inflammatory activity for drugs
      such as dexamethasone and butyrate in a human inflammatory bowel diseases whole
      blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC)
      cytokine mRNA expression levels were evaluated by quantitative SYBR Green real
      time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion
      in inflammatory bowel diseases patients' PBMC culture supernatants. There was a
      significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion,
      whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl
      butyrate administration, compared to that of butyrate alone at the highest
      concentration tested (100 microM), at 24h exposure. There was a significant
      decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion
      after dexamethasone loaded SLN administration, compared to dexamethasone alone at
      the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was
      detected under any conditions and no cytotoxic effects observed even at the
      highest concentration tested. The incorporation of butyrate and dexamethasone
      into SLN has a significant positive anti-inflammatory effect in the human
      inflammatory bowel disease whole-blood model.

PMID- 20138214
TI  - Shotgun proteomic analysis on the embryos of silkworm Bombyx mori at the end of
      organogenesis.
AB  - Embryonic development of silkworm, Bombyx mori is a process of systematical
      expression of genes and proteins which is dominated by complex regulatory
      networks. To gain comprehensive insight into the molecular basis of embryonic
      development and its regulation mechanisms, the proteome profile of the B. mori
      embryos at the end of organogenesis (tubercle appearance stage, TA) was
      characterized using LTQ-Orbitrap mass spectrometer. Totally 963 proteins were
      identified with a false discovery rate (FDR) of 0.12%. They were involved in
      embryonic development, chemoreception, and stimuli response and so forth. The
      proteins with the largest number of identified unique peptides, implying their
      possibly higher abundance, were involved in heat shock response, lipid transport
      and metabolism, and apoptosis. It was consistent with the physiological status of
      embryo at the end of organogenesis. Many functionally important proteins were
      identified for the first time in B. mori embryo such as the progesterone receptor
      membrane component 2, antennal binding protein, sericotropin, and molting fluid
      carboxypeptidase A (MF-CPA). 253 (26.27%) specific proteins in TA versus labrum
      appearance stage (LA, four days before TA) embryos were identified, which were
      mainly associated with musculature, nervous system, and chemoreception system.
      They disclosed the differential temporal and spatial expression of proteins in
      the process of organogenesis. The relative mRNA levels of fifteen identified
      proteins in the two experimented stages were also compared using quantitative
      reverse transcription PCR (qRT-PCR) and showed some inconsistencies with protein
      expression. Gene Ontology (GO) annotation of the identified proteins showed that
      the most proteome representations were in the categories of "binding" and
      "catalytic" in molecular function, and "cellular process" and "metabolic process"
      in biological process.

PMID- 20138215
TI  - Immortal coils: conserved dimerization motifs of the Drosophila ovulation
      prohormone ovulin.
AB  - Dimerization is an important feature of the function of some proteins, including
      prohormones. For proteins whose amino acid sequences evolve rapidly, it is
      unclear how such structural characteristics are retained biochemically. Here we
      address this question by focusing on ovulin, a prohormone that induces ovulation
      in Drosophila melanogaster females after mating. Ovulin is known to dimerize, and
      is one of the most rapidly evolving proteins encoded by the Drosophila genome. We
      show that residues within a previously hypothesized conserved dimerization domain
      (a coiled-coil) and a newly identified conserved dimerization domain (YxxxY)
      within ovulin are necessary for the formation of ovulin dimers. Moreover,
      dimerization is conserved in ovulin proteins from non-melanogaster species of
      Drosophila despite up to 80% sequence divergence. We show that heterospecific
      ovulin dimers can be formed in interspecies hybrid animals and in two-hybrid
      assays between ovulin proteins that are 15% diverged, indicating conservation of
      tertiary structure amidst a background of rapid sequence evolution. Our results
      suggest that because ovulin's self-interaction requires only small conserved
      domains, the rest of the molecule can be relatively tolerant to mutations.
      Consistent with this view, in comparisons of 8510 proteins across 6 species of
      Drosophila we find that rates of amino acid divergence are higher for proteins
      with coiled-coil protein-interaction domains than for non-coiled-coil proteins.

PMID- 20138216
TI  - Proteome profile in Myotonic Dystrophy type 2 myotubes reveals dysfunction in
      protein processing and mitochondrial pathways.
AB  - Myotonic Dystrophy type 2 (DM2) is caused by a DNA microsatellite expansion
      within the Zinc Finger Protein 9 gene leading to an abnormal splicing pattern
      largely responsible for the pathological condition. To better define the
      functional changes occurring in human DM2 myotubes we performed a quantitative
      proteome comparison between myotubes of DM2 and control patients using two
      dimensional gel electrophoresis followed by mass spectrometry. Our results
      indicate that the proteins, altered in DM2 cultures, belong to two major
      functional categories: i) mitochondrial components, with a reduction of EFTu,
      HSP60, GRP75 and Dienoyl-CoA-Isomerase, an enzyme involved in fatty acids
      degradation; ii) the ubiquitin proteasome system with increase of the 26S
      proteasome regulatory subunit 13 and a reduction of Proteasome subunit Alfa6 and
      of Rad23B homolog. Altered ubiquitin-proteasomal activity is supported by a
      global reduction of cytosolic ubiquitinated proteins. Although future work is
      required to clarify how these changes affect the degradation machinery and
      mitochondrial function and to evaluate if these changes also occur in the
      biopsies of DM2 patients, these results identify the mitochondrial proteins and
      the ubiquitin-proteasomal system as candidates potentially relevant to DM2
      pathogenesis.

PMID- 20138218
TI  - Phylogeny of hammerhead sharks (Family Sphyrnidae) inferred from mitochondrial
      and nuclear genes.
AB  - Hammerhead sharks (Family Sphyrnidae) get their name from their laterally
      expanded, dorsal-ventrally compressed head, a structure referred to as the
      cephalofoil. Species within the family vary for head size and shape and for body
      size in ways that are functionally significant. Here we infer the phylogeny for
      all species within the family based on analysis of mitochondrial and nuclear
      genes amounting to 6292 base pairs. Mixed model Bayesian analysis of the
      concatenated data and Bayesian estimation of the species tree (BEST) converged on
      the same topology of the relationships. Shimodaira-Hasegawa tests revealed that
      all previously proposed hypotheses could be refuted by the data. The new
      hypothesis for the group suggests that the ancestor of all extant sharks was
      large (>200 cms) and that small body size probably evolved twice at different
      times and places. Moreover, the results suggest that once the cephalofoil
      evolved, it underwent divergent evolution in different lineages presumably in
      response to unique selective regimes.

PMID- 20138217
TI  - A dynamic model of neurovascular coupling: implications for blood vessel dilation
      and constriction.
AB  - Neurovascular coupling in response to stimulation of the rat barrel cortex was
      investigated using concurrent multichannel electrophysiology and laser Doppler
      flowmetry. The data were used to build a linear dynamic model relating neural
      activity to blood flow. Local field potential time series were subject to current
      source density analysis, and the time series of a layer IV sink of the barrel
      cortex was used as the input to the model. The model output was the time series
      of the changes in regional cerebral blood flow (CBF). We show that this model can
      provide excellent fit of the CBF responses for stimulus durations of up to 16 s.
      The structure of the model consisted of two coupled components representing
      vascular dilation and constriction. The complex temporal characteristics of the
      CBF time series were reproduced by the relatively simple balance of these two
      components. We show that the impulse response obtained under the 16-s duration
      stimulation condition generalised to provide a good prediction to the data from
      the shorter duration stimulation conditions. Furthermore, by optimising three out
      of the total of nine model parameters, the variability in the data can be well
      accounted for over a wide range of stimulus conditions. By establishing
      linearity, classic system analysis methods can be used to generate and explore a
      range of equivalent model structures (e.g., feed-forward or feedback) to guide
      the experimental investigation of the control of vascular dilation and
      constriction following stimulation.

PMID- 20138219
TI  - Phylogenetic studies of sinipercid fish (Perciformes: Sinipercidae) based on
      multiple genes, with first application of an immune-related gene, the virus
      induced protein (viperin) gene.
AB  - The sinipercid fish represent a group of 12 species of freshwater percoid fish
      endemic to East Asia. To date published morphological and molecular phylogenetics
      hypotheses of sinipercid fish are part congruent, and there are some areas of
      significant disagreement with respect to species relationships. The present study
      used separate and combined methods to analyze 7307 bp of data from three
      mitochondrial genes (cyt b, CO1 and 16S rRNA; approximately 2312 bp) and three
      nuclear genes (viperin, the first two introns of S7 ribosomal protein gene;
      approximately 4995 bp) for the attempts to estimate the relationships among
      sinipercids and to assess the phylogenetic utility of these markers. Phylogenetic
      trees were reconstructed using maximum parsimony, maximum likelihood and
      partitioned Bayesian analyses. Despite the detection of significant heterogeneity
      of phylogenetic signal between the mitochondrial and nuclear partitions, the
      combined data analysis represented the best-supported topology of all data. The
      sinipercid fish form a monophyletic group with two distinct clades, one
      corresponding to the genus Siniperca and the other to Coreoperca. Coreoperca
      whiteheadi is the sister taxon to Coreoperca herzi plus Coreoperca kawamebari. In
      the Siniperca, Siniperca undulata is the sister taxon to the other members of
      Siniperca, within the subclade containing the other members of the genus,
      Siniperca chuatsi and Siniperca kneri are sister species, next joined by
      Siniperca obscura, Siniperca roulei, Sinipercascherzeri and finally by Siniperca
      fortis. The potential utilities of six different genes for phylogenetic
      resolution of closely related sinipercid species were also evaluated, with
      special interest in that of the novel virus-induced protein (viperin) gene.

PMID- 20138220
TI  - Pattern and timing of diversification of the mammalian order Carnivora inferred
      from multiple nuclear gene sequences.
AB  - The mammalian order Carnivora has attracted the attention of scientists of
      various disciplines for decades, leading to intense interest in defining its
      supra-familial relationships. In the last few years, major changes to the
      topological structure of the carnivoran tree have been proposed and supported by
      various molecular data sets, radically changing the traditional view of family
      composition in this order. Although a sequence of molecular studies have
      established a growing consensus with respect to most inter-familial
      relationships, no analysis so far has included all carnivoran lineages (both
      feliform and caniform) in an integrated data set, so as to determine comparative
      patterns of diversification. Moreover, no study conducted thus far has estimated
      divergence dates among all carnivoran families, which is an important requirement
      in the attempt to understand the patterns and tempo of diversification in this
      group. In this study, we have investigated the phylogenetic relationships among
      carnivoran families, and performed molecular dating analyses of the inferred
      nodes. We assembled a molecular supermatrix containing 14 genes (7765 bp), most
      of which have not been previously used in supra-familial carnivoran
      phylogenetics, for 50 different genera representing all carnivoran families.
      Analysis of this data set led to consistent and robust resolution of all supra
      familial nodes in the carnivoran tree, and allowed the construction of a
      molecular timescale for the evolution of this mammalian order.

PMID- 20138221
TI  - Phylogenetic relationships and divergence dates of the whole mitochondrial genome
      sequences among three gibbon genera.
AB  - Phylogenetic relationships of gibbons (4 genera, 12 species) deduced from
      short/partial mitochondrial DNA sequences were with low resolution and
      inconsistent. Their divergence over the short period of time may require longer
      sequences for the higher resolution. To solve the problems, we newly sequenced
      the whole mitochondrial genome of Hylobates agilis, Hylobates pileatus, Nomascus
      sp. and Symphalangus syndactylus. A highly resolved phylogenetic tree was
      obtained for the mitochondrial genome in the neighbor-joining, maximum-parsimony
      and maximum-likelihood analyses. The divergence dates of mitochondrial genome
      were estimated by Bayesian method; Nomascus and the other two genera to 8.0
      million years ago (MYA), Symphalangus and Hylobates to 7.0 MYA, Hylobates
      pileatus and the other two Hylobates species to 3.9 MYA and Hylobates lar and
      Hylobates agilis to 3.3 MYA. Our results support the generic rank of Nomascus,
      Symphalangus and Hylobates, and proposed a new scenario that the Hylobates
      gibbons diverged in the Pliocene. This study shows the potential of the whole
      mitochondrial genome analyses to reveal detailed divergence history of gibbons.

PMID- 20138222
TI  - Introgressive hybridization in North American hakes after secondary contact.
AB  - High levels of bidirectional introgressive hybridization were found between the
      two Atlantic North American hakes Merluccius albidus and M. bilinearis in their
      overlapping distribution area between the 34 and the 42 degrees N parallels,
      employing mitochondrial and nuclear DNA markers. Absence of F(1) hybrids, and
      varied levels of bidirectional introgression, indicate long-time hybridization
      and backcrossing. Based on the evolutionary history of the genus Merluccius,
      originated in this area from the ancestor of the present M. bilinearis by the
      rise of the Panama Isthmus, secondary contact between the two species has
      probably been promoted by northwards displacement of M. albidus. Higher
      introgression rates in southern areas of M. albidus could be explained by
      restricted gene flow in that area which may allow long-term accumulation of
      introgressed genes.

PMID- 20138223
TI  - Molecular systematics and evolutionary biogeography of the genus Talpa
      (Soricomorpha: Talpidae).
AB  - The range of the genus Talpa covers almost all Europe up to Western Asia. This
      genus has never been the object of comprehensive systematic studies using
      molecular and genetic techniques, such that the evolutionary relationships among
      species remain unclear. Talpa shows high levels of endemism, and the influence of
      past glaciation cycles on the distribution pattern of several species has been
      hypothesized. In this work, we assessed the molecular systematics of the genus
      using the mitochondrial gene cytochrome b from eight of the nine extant species
      of Talpa moles. Furthermore, molecular clock estimations were used to hypothesize
      a biogeographic scenario in concordance with fossil data. Results suggest a
      monophyletic origin of the genus and a common ancestor for the western European
      moles T. europaea, T. caeca, T. romana and T. occidentalis. The eastern species
      T. altaica and T. caucasica are basally divergent. The estimated ages of
      divergence among lineages are in accordance with a Miocene origin of the extant
      moles. The genus likely originated in Asia, spreading into Europe during the
      Pliocene. The evolution of moles appears to have been driven by changes in
      moisture levels that influenced extinction and speciation events during the
      Miocene and the Pliocene. Pleistocene climatic oscillations likely caused the
      range shrinkages and expansions that led to the current distribution pattern of
      most Talpa species.

PMID- 20138224
TI  - Supermatrix and species tree methods resolve phylogenetic relationships within
      the big cats, Panthera (Carnivora: Felidae).
AB  - The pantherine lineage of cats diverged from the remainder of modern Felidae less
      than 11 million years ago and consists of the five big cats of the genus
      Panthera, the lion, tiger, jaguar, leopard, and snow leopard, as well as the
      closely related clouded leopard. A significant problem exists with respect to the
      precise phylogeny of these highly threatened great cats. Despite multiple
      publications on the subject, no two molecular studies have reconstructed Panthera
      with the same topology. These evolutionary relationships remain unresolved
      partially due to the recent and rapid radiation of pantherines in the Pliocene,
      individual speciation events occurring within less than 1 million years, and
      probable introgression between lineages following their divergence. We provide an
      alternative, highly supported interpretation of the evolutionary history of the
      pantherine lineage using novel and published DNA sequence data from the
      autosomes, both sex chromosomes and the mitochondrial genome. New sequences were
      generated for 39 single-copy regions of the felid Y chromosome, as well as four
      mitochondrial and four autosomal gene segments, totaling 28.7 kb. Phylogenetic
      analysis of these new data, combined with all published data in GenBank,
      highlighted the prevalence of phylogenetic disparities stemming either from the
      amplification of a mitochondrial to nuclear translocation event (numt), or errors
      in species identification. Our 47.6 kb combined dataset was analyzed as a
      supermatrix and with respect to individual partitions using maximum likelihood
      and Bayesian phylogenetic inference, in conjunction with Bayesian Estimation of
      Species Trees (BEST) which accounts for heterogeneous gene histories. Our results
      yield a robust consensus topology supporting the monophyly of lion and leopard,
      with jaguar sister to these species, as well as a sister species relationship of
      tiger and snow leopard. These results highlight new avenues for the study of
      speciation genomics and understanding the historical events surrounding the
      origin of the members of this lineage.

PMID- 20138225
TI  - Systematic relationships and taxonomy of Suncus montanus and S. murinus from Sri
      Lanka.
AB  - Here we use nuclear and mitochondrial DNA sequence data, combined with
      morphometric analyses, to clarify the systematic relationships and taxonomy of
      two complex species of shrews, Suncus montanus and S. murinus, in Sri Lanka. We
      find that subspecies of S. murinus, Suncus murinus murinus from Anuaradhapura and
      S. m. caerulescens from Colombo, show little or no genetic difference in the
      mitochondrial (cytochrome-b and 16SrRNA) and nuclear (Rag 1, aldolase C and EF-1
      alpha intron) genes, confirming their classification as a single species.
      However, two populations of S. murinus from Peradeniya and Udawalawe are
      identified as putative hybrids of S. murinus and S. montanus. Shrews collected
      from Peradeniya are best described as a population of S. murinus, but could be
      identified as S.m. kandianus using morphological features. Nuclear DNA sequence
      data places this population in a clade with other S. murinus, but mtDNA sequences
      of the population nests within a clade of S. montanus haplotypes. This discordant
      pattern of nuclear and mitochondrial genes suggests either hybridization between
      S. murinus and S. montanus or introgression of S. montanus mitochondrial DNA into
      S. m. kandianus. S. m. murinus from Udawalawe, which shows no distinct
      morphological difference from S. m. murinus from Anuradhapura, falls in the clade
      of S. murinus in both nuclear and mitochondrial trees. In the nuclear gene tree
      however, S. m.murinus from Udawalawe is placed as a sister taxon to the clade
      including other S. murinus. Rag 1 gene sequences in Udawalawe individuals suggest
      recombination of S. murinus and S. montanus DNA within the gene. However,
      additional nuclear genes are necessary to study the extent of the hybridization
      of S. murinus and S. montanus.

PMID- 20138226
TI  - Evaluation of response in hepatitic variant of acute liver graft-versus-host
      disease.

PMID- 20138227
TI  - Targeted agents for chronic myelogenous leukemia: will that be the end of
      allogeneic bone marrow transplantation for that disease?
AB  - Although the drug imatinib has been accepted as the treatment of choice for
      chronic myelogenous leukemia (CML) in chronic phase (CP) throughout the Western
      world, allogeneic stem cell transplantation (allo-SCT) continues to remain a
      widely practiced first-line treatment in countries with limited health care
      budgets. The rationale is not scientific, but largely economically based. We
      analyzed a cohort of 46 CML patients who participated in a graft-versus-host
      disease (GVHD) prophylaxis clinical trial and underwent related HLA-matched
      allogeneic peripheral blood stem cell transplantation. The median time of follow
      up in surviving patients was 43 months (range: 4-89 months). Risk stratification
      of the population was done by European Blood and Marrow Transplant (EBMT)
      criteria. The estimated probabilities of overall survival (OS) and leukemia-free
      survival (LFS) at 3 years in low EBMT risk score (0-2) patients were both 91%,
      respectively. We conclude that in countries with restricted access to imatinib,
      allo-SCT should be considered early on as front-line therapy. Continued research
      support for bone marrow transplantation will be needed to make a global impact on
      this disease.

PMID- 20138229
TI  - Dendritic cell count in the graft predicts relapse in patients with hematologic
      malignancies undergoing an HLA-matched related allogeneic peripheral blood stem
      cell transplant.
AB  - We investigated the impact of the number of infused and reconstituted
      immunocompetent cells including dendritic cells (DCs) on clinical outcome of
      patients with hematologic malignancies undergoing an allogeneic peripheral blood
      stem cell transplantation. Sixty-nine consecutive patients with hematologic
      malignancies were included in the analysis. The median age of the cohort was 32
      years (range: 2-62 years) and there were 39 (57%) males. Twenty-one (30%)
      patients relapsed with a cumulative incidence of 44 % +/- 14% at a median follow
      up of 28 months. On a multivariate analysis, a high plasmacytoid dendritic cell
      (PC) content in the graft was associated with higher risk of relapse. The
      patients were further categorized based on the median PC counts in the graft as
      high (> or =2.3 x 10(6)/kg) and low (<2.3 x 10(6)/kg) groups. The baseline
      characteristics of these 2 groups were comparable. The group that had a high PC
      content in the graft had significantly higher risk of relapse and lower overall
      survival (OS) and event-free survival (EFS). Our data suggests that PC content in
      the graft predicts clinical outcomes such as relapse and survival in patients
      with hematologic malignancies undergoing an allogeneic HLA matched related
      peripheral blood stem cell transplantation. There is potential for pretransplant
      manipulation of this cellular subset in the graft.

PMID- 20138230
TI  - Editorial.

PMID- 20138231
TI  - Heat shock protein gene expression and function in amphibian model systems.
AB  - Heat shock proteins (HSPs) are molecular chaperones that are involved in protein
      folding and translocation. During heat shock, both constitutive and stress
      inducible HSPs bind to and inhibit irreversible aggregation of denatured protein
      and facilitate their refolding once normal cellular conditions are re
      established. Recent interest in HSPs has been propelled by their association with
      various human diseases. Amphibian model systems, as shown in this review, have
      had a significant impact on our understanding of hsp gene expression and
      function. Some amphibian hsp genes are expressed constitutively during oogenesis
      and embryogenesis, while others are developmentally regulated and enriched in
      selected tissues in a stress-inducible fashion. For example, while hsp70 genes
      are heat-inducible after the midblastula stage, hsp30 genes are not inducible
      until late neurula/early tailbud. This particular phenomenon is likely controlled
      by chromatin structure. Also, hsp genes are expressed during regeneration,
      primarily in response to wounding-associated trauma. The availability of
      amphibian cultured cells has enabled the analysis of hsp gene expression induced
      by different stresses (e.g. cadmium, arsenite, proteasome inhibitors etc.), HSP
      intracellular localization, and their involvement in stress resistance.
      Furthermore, hyperthermia treatment of adult amphibians reveals that certain
      tissues were more sensitive than others in terms of hsp gene expression. Finally,
      this review details the evidence available for the role of amphibian small HSPs
      as molecular chaperones.

PMID- 20138232
TI  - A close relationship between androgen levels and eumelanogenesis in the teleost
      red seabream (Pagrus major): Quantitative analysis of its seasonal variation and
      effects of oral treatment with methyl-testosterone.
AB  - Male and female teleost seabream (Pagrus major) were examined for seasonal
      variation of eumelanin, pheomelanin, 11-ketotestosterone (11KT, fish androgen),
      lightness (L* value) and Gonad Somatic Index (GSI: gonad mass/body massx100). In
      males, levels of pyrrole-2,3,5-tricarboxylic acid (a marker of eumelanin), 11KT
      and the GSI increased sharply from September and plateaued in March and April
      when the fish are sexually mature. These results are consistent with the
      lightness of their body color. Using the data from males, a high correlation was
      observed for all combinations of those four variables (PTCA, 11KT, lightness and
      GSI). In females, little change was observed in those variables except for the
      GSI. 4-Amino-3-hydroxyphenylalanine (a marker of pheomelanin) was also analyzed,
      but it was below the detection limit at all times. Oral treatment of juvenile red
      seabream with synthetic androgen methyl-testosterone for 2 months induced
      eumelanin accumulation about 3 times higher than the control. These data show
      that there is a close relationship between androgen levels and eumelanin
      accumulation in teleosts. This is the first report that androgen affects melanin
      accumulation in a dose-dependent manner.

PMID- 20138233
TI  - Eicosanoids mediate hemolymph oxidative and antioxidative response in larvae of
      Galleria mellonella L.
AB  - Antioxidant enzymes play a major role in the defense against pro-oxidative
      effects of xenobiotics and pro-oxidant plant allelochemicals in insects. We posed
      the hypothesis that eicosanoids also mediate antioxidant enzymatic defense
      reactions to pro-oxidant challenge. To test this idea, we reared first-instar
      larvae of Galleria mellonella (L.) with the lypoxygenase inhibitor, esculetin
      (0.001%), the phospholipase A(2) inhibitor, dexamethasone (0.001%) and the dual
      inhibitor of cyclooxygenase and lipoxygenase, phenidone (0.1%) to seventh
      instars. Newly ecdysed seventh-instars were then fed on artificial diet
      containing 0.05% xanthotoxin (XA) for 2 days. Treating seventh-instar larvae of
      G. mellonella with XA induced lipid peroxidation and protein carbonylation as
      evident from the increased content of malondialdehyde (MDA) and protein carbonyls
      respectively, and antioxidative enzymatic response in a dose-dependent manner.
      High dietary XA concentrations (0.005 and 0.1%) were associated with increasing
      MDA and carbonyl content (by 3-fold) and antioxidant enzyme activities,
      superoxide dismutase (SOD) (by 3-fold) and catalase (CAT) (by 4-fold), and
      glutathione-dependent enzymes, glutathione S-transferase (GST) (by 15-fold) and
      glutathione peroxidase (GPx) (by 7-fold). Relative to control, eicosanoid
      biosynthesis inhibitors (EBIs) esculetin, dexamethasone and phenidone also
      resulted in impaired MDA content and antioxidant enzyme activities. However,
      carbonyl content did not differ between control- and EBIs-feeding larvae.
      Finally, MDA and carbonyl content, and antioxidant enzymes SOD, GST and GPx
      activities exhibited an incremental increase while CAT activity was decreased in
      the experimental larvae that had been reared on media amended with esculetin,
      dexamethasone and phenidone and then challenged with our standard XA challenge
      dose. Two of the markers indicated that significantly higher levels of oxidative
      stress were produced in the hemolymph tissue of larvae fed diets supplemented
      with EBIs and then challenged with XA. This oxidative stress was associated with
      elicited antioxidative responses by increasing SOD, GST and GPx and decreasing
      CAT activities in hemolymph. We infer from these findings that eicosanoids
      mediate insect antioxidant enzymatic responses to dietary pro-oxidants.

PMID- 20138234
TI  - Ghrelin affects carbohydrate-glycogen metabolism via insulin inhibition and
      glucagon stimulation in the zebrafish (Danio rerio) brain.
AB  - Carbohydrate-glycogen metabolism (CGM) is critical for emergency energy supplies
      in the central nervous system (CNS). Ghrelin (GHRL) in pancreas is known to
      significantly regulate a dominant player in CGM, insulin (INS). However, its
      regulatory effect on extrapancreatic INS synthesis is yet unknown. In this study,
      we used adult zebrafish to elucidate the expression and role of zebrafish GHRL
      (zGHRL) in genes primarily involved in the brain's CGM. Results showed that
      zebrafish brain expressed zghrl and its receptor, growth hormone secretagogue
      receptor (GHS-R: zghs-r1a and zghs-r2a), according to RT-PCR and in situ
      hybridization. Protein localization coupled with mRNA spatial expression further
      verified zGHRL's presence in the brain. For the in vivo study, significant
      increases in zghs-r1a and zghs-r2a synthesis were observed after injection of
      synthetic peptide goldfish GHRL-12 (gGHRL) using brain templates analyzed by
      quantitative real-time PCR (qPCR). Ligand-receptor synthesis of INS (zinsa; zins
      r1 and zins-r2) significantly decreased, while glucagon (GCG) (zgcgb1 and zgcgb2;
      zgcg-r1 and zgcg-r2) exhibited a significant transient increase. In CGM,
      subsequent processes indicate urgent glucose-sensing response that will balance
      glycogen degradation and energy storage. Taken together, these findings suggest
      that GHRL regulates INS synthesis by mediating its action on GHS-R in the CNS and
      partly involved in CGM.

PMID- 20138235
TI  - A new role for photoresponsive neurons called simple photoreceptors in the sea
      slug Onchidium verruculatum: Potentiation of synaptic transmission and motor
      response.
AB  - The simple photoreceptors Ip-1 and Ip-2 are intrinsically light-sensitive neurons
      that exist in the abdominal ganglion of the sea slug Onchidium verruculatum.
      Using isolated ganglia and semi-intact or intact animal preparations, the present
      studies examined the light-sensing and physiological roles of Ip-1 and Ip-2
      cells, which respond jointly to light by inducing a slow hyperpolarizing receptor
      potential. First, the synaptic inputs received by Ip-1 and Ip-2 and the axonal
      branches arising from their cell bodies were investigated. We found that these
      cells are not only first-order photosensory neurons, but also second-order
      neurons (interneurons), relaying inhibitory synaptic inputs such as water
      pressure and/or tactile senses. The amphibian Onchidium opens a pneumostome at
      low tide in order to aero-breathe. This pneumostome opening; i.e., aero-breathing
      behavior, was produced by spike discharges of Ip-1 and Ip-2 cells. Furthermore,
      the present results suggested that the hyperpolarizing photoresponse of Ip-1 and
      Ip-2 cells operates in the potentiation of inhibitory sensory synaptic
      transmission. Thus, we conclude that the simple photoreceptors of Onchidium play
      a role in the long-lasting potentiation of synaptic transmission and the
      subsequent behavioral response and so may be involved in a new photosensory
      modality, non-image-forming vision.

PMID- 20138236
TI  - The effect of exercise training on the metabolic interaction between digestion
      and locomotion in juvenile darkbarbel catfish (Peltebagrus vachelli).
AB  - To examine the effects of exercise training on the metabolic interaction between
      digestion and locomotion in juvenile darkbarbel catfish (Peltebagrus vachelli)
      (5.58+/-0.04 g), the postprandial metabolic response, critical swimming speeds
      (U(crit)) and oxygen consumption rates (VO(2)) during swimming were measured on
      fish held at a constant temperature (25 degrees C). Fish were fed a diet of
      cutlets of freshly killed loach. Fish in the trained group were forced to swim at
      60% U(crit) for 50 min followed by an exhaustive 10-min chase once daily for 21
      days. Exercise training did not produce significant differences in resting VO(2)
      (VO(2rest)) and postprandial peak VO(2) (VO(2peak)) compared to the non-trained
      groups. However, exercise training elicited a significant decrease in both the
      duration and energy expenditure of digestion when fed with similar food (P<0.05).
      Feeding had no significant effect on U(crit) of non-trained fish, while it caused
      a significantly lower U(crit) (compared to fasting fish) in trained fish
      (P<0.05). Training resulted in a significantly higher U(crit) and active VO(2)
      (VO(2active)) in fasting fish when fish swam at U(crit). However, training had no
      effect on either the U(crit) or VO(2active) of post-feeding fish. Our results
      suggest that: (1) the central cardio-respiratory systems of non-trained
      darkbarbel catfish can support the oxygen demands of both digestion and the
      locomotion simultaneously; (2) the metabolic mode of competition in darkbarbel
      catfish is flexible; it changed from an additive model to a digestion-priority
      model after exercise training; (3) training may be accounted for cardio
      respiratory capacity increase and following improvement of swimming performance
      during fasting in darkbarbel catfish, although, the swimming capacity was
      sacrificed to digestion in the situation of postprandial locomotion.

PMID- 20138237
TI  - Energetics and kinematics of walking in the barnacle goose (Branta leucopsis).
AB  - Barnacle geese were walked on a treadmill at speeds ranging from 0.25 to 1.25 ms(
      1), which was their highest sustainable speed. No evidence for a gait change was
      found. The gait of a barnacle goose appears to conform to the classical pendulum
      mechanics based model of walking, with the kinetic energy of forward motion
      (horizontal kinetic energy, E(kh)) out-of-phase with the sum of the gravitational
      potential (E(p)), and vertical kinetic (E(kv)) energies of the centre of mass at
      all speeds. Why barnacle geese are unable to aerial run when other 'waddling'
      species do show an aerial phase (e.g., mallard ducks) is unclear. Presumably,
      however, it is likely to relate to the amount of lateral kinetic energy
      generated, which is a feature of 'waddling'. We predict that lateral kinetic
      energy generated by barnacle geese and other waddling species that cannot aerial
      run, is higher than in those that can. Due to competing selection pressures for
      swimming and flight, barnacle geese are mechanically and energetically
      inefficient walkers relative to more specialist cursorial birds. Their upper
      walking speed, however, appears to be limited by morphology (via kinematics) and
      not metabolic capacity (energetics).

PMID- 20138238
TI  - Identification of a developmentally and hormonally regulated Delta-Class
      glutathione S-transferase in rice moth Corcyra cephalonica.
AB  - Glutathione S-transferases (GSTs) are a large family of multifunctional enzymes,
      known for their role in cellular detoxification. Here we report a cytosolic GST
      with optimal activity at alkaline pH (8.3) from the visceral fat body of late
      last instar (LLI) larvae of a lepidopteran insect rice moth Corcyra cephalonica.
      All previously known GSTs are active between pH 6.0 to 6.5. Purification and
      characterization revealed the Corcyra cephalonica GST (CcGST) as a 23-kDa
      protein. HPLC and 2D analysis showed a single isoform of the protein in the LLI
      visceral fat body. Degenerate primer based method identified a 701-nucleotide
      cDNA and the longest open reading frame contained 216 amino acids. Multiple
      sequence and structural alignment showed close similarity with delta-class GSTs.
      CcGST is present mainly in the fat body with highest activity at the late-last
      instar larval stage. Juvenile hormone (JH) negatively inhibits the CcGST activity
      both ex vivo and in vivo. We speculate that high expression and activity of CcGST
      in the fat body of the late-last instar larvae, when endogenous JH titer is low
      may have role in the insect post-embryonic development unrelated to their
      previously known function.

PMID- 20138239
TI  - Activation of TM7SF2 promoter by SREBP-2 depends on a new sterol regulatory
      element, a GC-box, and an inverted CCAAT-box.
AB  - TM7SF2 gene encodes 3beta-hydroxysterol Delta(14)-reductase, responsible for the
      reduction of C14-unsaturated sterols in cholesterol biosynthesis. TM7SF2 gene
      expression is controlled by cell sterol levels through the SREBP-2. The motifs of
      TM7SF2 promoter responsible for activation by SREBP-2 have not been
      characterized. Using electrophoretic mobility shift assays and mutation analysis,
      we identified a new SRE motif, 60% identical to an inverted SRE-3, able to bind
      SREBP-2 in vitro and in vivo. Co-transfection of promoter-luciferase reporter
      constructs in HepG2 cells showed that the binding of SREBP-2 to SRE produced
      approximately 26-fold promoter activation, whereas mutation of the SRE motif
      caused a dramatic decrease of transactivation by SREBP-2. The function of
      additional motifs that bind transcription factors cooperating with SREBP-2 was
      investigated. An inverted CCAAT-box, that binds nuclear factor Y (NF-Y),
      cooperates with SREBP-2 in TM7SF2 promoter activation. Deletion of this motif
      resulted in the loss of promoter induction by sterol starvation in HepG2 cells,
      as well as a decrease in fold activation by SREBP-2 in co-transfection
      experiments. Moreover, co-transfection of the promoter with a plasmid expressing
      dominant negative NF-YA did not permit full activation by SREBP-2. Three GC-boxes
      (1, 2, 3), known to bind Sp1 transcription factor, were also investigated. The
      mutagenesis of each of them produced a decrease in SREBP-2-dependent activation,
      the most powerful being GC-box2. A triple mutagenized promoter construct did not
      have an additive effect. We conclude that, besides the SRE motif, both the
      inverted CCAAT-box and GC-box2 are essential for full promoter activation by
      SREBP-2.

PMID- 20138240
TI  - Biological and molecular responses of Chironomus riparius (Diptera, Chironomidae)
      to herbicide 2,4-D (2,4-dichlorophenoxyacetic acid).
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) is an agricultural contaminant found in
      rural ground water. It remains to be determined whether neither 2,4-D poses
      environmental risks, nor is the mechanism of toxicity known at the molecular
      level. To evaluate the potential ecological risk of 2,4-D, we assessed the
      biological parameters including the survival rate, adult sex ratio of emerged
      adults, and mouthpart deformities in Chironomus riparius after long-term exposure
      to 2,4-D. The larvae were treated with 0.1, 1 or, 10microgL(-1) of 2,4-D for
      short- and long-term exposure periods. The sex ratio was changed in C. riparius
      exposed to only 10microgL(-1) of 2,4-D, whereas mouthpart deformities were
      observed as significantly higher in C. riparius exposed to 0.1microgL(-1) of 2,4
      D. Survival rates were not significantly affected by 2,4-D. Furthermore, we
      evaluated the molecular and biochemical responses of biomarker genes such as gene
      expression of heat shock proteins (HSPs), ferritins and glutathione S
      transferases (GSTs) in C. riparius exposed to 2,4-D for 24h. The expressions of
      HSP70, HSP40, HSP90 and GST levels in C. riparius were significantly increased
      after exposure to a 10microgL(-1) concentration of 2,4-D, whereas ferritin heavy
      and light chain gene expressions were significantly increased at all
      concentrations of 2,4-D exposure. Finally, these results may provide an important
      contribution to our understanding of the toxicology of 2,4-D herbicide in C.
      riparius. Moreover, the 2,4-D-mediated gene expressions may be generated by 2,4-D
      is the causative effects on most probable cause of the observed alterations.
      These biological, molecular and morphological parameters and the measured
      parameters can be used to monitor 2,4-D toxicity in an aquatic environment.

PMID- 20138241
TI  - Dexamethasone facilitates lipid accumulation and mild feed restriction improves
      fatty acids oxidation in skeletal muscle of broiler chicks (Gallus gallus
      domesticus).
AB  - Effects of dexamethasone (DEX) and mild feed restriction on the uptake and
      utilization of fatty acids in skeletal muscle of broiler chicks (Gallus gallus
      domesticus) were investigated. Male Arbor Acres chicks (7-days old, n=30) were
      injected with DEX or saline for 3days, and a feed restriction group was included.
      DEX enhanced circulating very low density lipoprotein (VLDL) level and the lipid
      accumulation in both adipose and skeletal muscle tissues. Compared with the
      control, liver-carnitine palmitoyltransferase 1 (L-CPT1) and AMP-activated
      protein kinase (AMPK) alpha2 mRNA level of M. biceps femoris (BF) were down
      regulated significantly by DEX, while mRNA expression of lipoprotein lipase
      (LPL), fatty acid transport protein 1 (FATP1), heart-fatty acid binding protein
      (H-FABP), long-chain acyl-CoA dehydrogenase (LCAD), activities of LPL and AMPK in
      both skeletal muscles were not obviously affected. Feed restriction increased the
      mRNA expression of LPL, L-CPT1 and LCAD of M. pectoralis major (PM), and FATP1, H
      FABP, L-CPT1 and LCAD of BF. In conclusion, DEX retards the growth of body mass
      but facilitates lipid accumulation in both adipose and skeletal muscle tissues.
      In contrast to the favorable effect of mild feed restriction, DEX did not alter
      the uptake of fatty acids in the skeletal muscle. The result suggests that DEX
      may promote intramyocellular lipid accumulation by suppressed fatty acid
      oxidation while mild feed restriction improved fatty acid oxidation in skeletal
      muscle, especially in red muscle. Glucocorticoids (GCs) regulated muscle fatty
      acid metabolism in a different way from energy deficit caused by mild feed
      restriction.

PMID- 20138242
TI  - Hepatoma-targeted gene delivery using a tumor cell-specific gene regulation
      system combined with a human liver cell-specific bionanocapsule.
AB  - Hepatoma (hepatocellular carcinoma) is the most common type of malignant tumor
      originating in the liver and has a relatively low 5-year survival rate. The
      development of hepatoma-targeted therapy is needed to increase treatment
      efficiency and to reduce the incidence of undesirable side effects. In this study
      we developed a novel hepatoma-targeted gene delivery system. The gene delivery
      system was prepared by combining a human liver cell-specific bionanocapsule (BNC)
      and a tumor cell-specific gene regulation polymer, which responds to
      hyperactivated protein kinase C alpha in hepatoma cells. The complex of the
      polymer-DNA with BNCs was delivered into cells and tissues. The developed system
      showed increased transfection efficiency and resulted in cell-specific gene
      expression in hepatoma cells and tissues (HuH-7), but no gene expression in
      normal human hepatocytes or human epidermoid tumor cells (A431). The combination
      of a tumor cell-specific gene regulation system responding to protein kinase C
      alpha and BNCs showed excellent potential for the selective treatment of
      hepatomas. The system could be a useful method with applications in hepatoma
      specific gene therapy and molecular imaging. From the clinical editor:
      Hepatocellular carcinoma is the most common type of malignant tumor in the liver
      with a low 5-year survival rate. In this study, a novel hepatoma-targeted gene
      delivery system was prepared by combining a human liver cell-specific
      bionanocapsule and a tumor cell-specific gene regulation polymer, which responds
      to hyperactivated protein kinase C (PKC)a in hepatoma cells. The system could be
      a useful in hepatoma-specific gene therapy and molecular imaging.

PMID- 20138243
TI  - Uptake and distribution of fullerenes in human mast cells.
AB  - Fullerenes are carbon cages of variable size that can be derivatized with various
      side chain moieties resulting in compounds that are being developed into
      nanomedicines. Although fullerene use in several preclinical in vitro and in vivo
      models of disease has demonstrated their potential as diagnostic and therapeutic
      agents, little is known about how they enter cells, what organelles they target,
      and the time course for their cellular deposition. Fullerenes (C(70)) that have
      already been shown to be potent inhibitors of mast cell (MC)-mediated allergic
      inflammation were conjugated with Texas red (TR) and used in conjunction with
      confocal microscopy to determine mechanisms of uptake, the organelle
      localization, and the duration they can be detected in situ. We show that C(70)
      TR are nonspecifically endocytosed into MCs, where they are shuttled throughout
      the cytoplasm, lysosomes, mitochondria, and into endoplasmic reticulum at
      different times. No nuclear or secretory granule localization was observed. The
      C(70)-TR remained detectable within cells at 1 week. These studies show that MCs
      endocytose fullerenes, where they are shuttled to organelles involved with
      calcium and reactive oxygen species production, which may explain their efficacy
      as cellular inhibitors. From the clinical editor: Fullerenes are carbon cages of
      variable size that have already been shown to be potent inhibitors of mast cell
      (MC)-mediated allergic inflammation. These were conjugated with Texas red (TR)
      and used in conjunction with confocal microscopy to determine mechanisms of
      uptake, the organelle localization, and duration, demonstrating that MCs
      endocytose fullerenes, which are shuttled to organelles involved with calcium and
      reactive oxygen species production. This intracellular trafficking may explain
      the efficacy of fullerenes as cellular inhibitors.

PMID- 20138245
TI  - Accurate quantitation of glutathione in cell lysates through surface-assisted
      laser desorption/ionization mass spectrometry using gold nanoparticles.
AB  - We developed a method for the determination of three aminothiols--cysteine,
      glutathione (GSH), and homocysteine--using surface-assisted laser
      desorption/ionization mass spectrometry (SALDI-MS). The analytes were first
      captured using the unmodified 14-nm gold nanoparticles; N-2
      mercaptopropionylglycine-modified gold nanoparticles serving as internal standard
      were sequentially added, and then the sample was analyzed using SALDI-MS. This
      approach provided good quantitative linearity of the three analytes (R(2) =
      approximately 0.99), with good reproducibility (relative standard deviations:
      <10%), in the analyses of GSH in the lysates of human red blood cells and MCF-7
      cancer breast cells in the presence and absence of the anti-inflammatory drug
      sulfasalazine. The internal-standard SALDI-MS approach provides simplicity,
      accuracy, and precision to the determination of GSH in cells under drug invasion,
      to open an avenue for SALDI-MS to be used for the precise quantitative
      determination of a variety of analytes. From the clinical editor: This paper
      reports the development of a surface assisted laser desorption/ionization mass
      spectrometry method to precisely determine aminothiols-cysteine (Cys),
      glutathione (GSH), and homocysteine (HCys).

PMID- 20138244
TI  - Nanotopographical modification: a regulator of cellular function through focal
      adhesions.
AB  - As materials technology and the field of biomedical engineering advances, the
      role of cellular mechanisms, in particular adhesive interactions with implantable
      devices, becomes more relevant in both research and clinical practice. A key
      tenet of medical device design has evolved from the exquisite ability of
      biological systems to respond to topographical features or chemical stimuli, a
      process that has led to the development of next-generation biomaterials for a
      wide variety of clinical disorders. In vitro studies have identified nanoscale
      features as potent modulators of cellular behavior through the onset of focal
      adhesion formation. The focus of this review is on the recent developments
      concerning the role of nanoscale structures on integrin-mediated adhesion and
      cellular function with an emphasis on the generation of medical constructs with
      regenerative applications. FROM THE CLINICAL EDITOR: In this review, recent
      developments related to the role of nanoscale structures on integrin-mediated
      adhesion and cellular function is discussed, with an emphasis on regenerative
      applications.

PMID- 20138246
TI  - Landscape phage fusion protein-mediated targeting of nanomedicines enhances their
      prostate tumor cell association and cytotoxic efficiency.
AB  - Tumor-specific cytotoxicity of drugs can be enhanced by targeting them to tumor
      receptors using tumor-specific ligands. Phage display offers a high-throughput
      approach to screen for the targeting ligands. We have successfully isolated phage
      fusion peptides selective and specific for PC3 prostate cancer cells. Also, we
      have demonstrated a novel approach of targeting liposomes through tumor-specific
      phage fusion coat proteins, exploiting the intrinsic properties of the phage coat
      protein as an integral membrane protein. Here we describe the production of
      Rhodamine-labeled liposomes as well as doxorubicin-loaded long-circulating
      liposomes targeted to PC3 prostate tumor cells via PC-specific phage peptides, as
      an extension of our previous studies. Targeting of labeled liposomes was
      demonstrated using fluorescence microscopy as well as flow cytometry. Targeting
      of doxorubicin-loaded liposomes enhanced their cytotoxic effect against PC3 cells
      in vitro, indicating a possible therapeutic advantage. The simplicity of the
      approach for generating targeted liposomes coupled with the ability to rapidly
      obtain tumor-specific phage fusion proteins via phage display may contribute to a
      combinatorial system for the production of targeted liposomal therapeutics for
      advanced stages of prostate tumor. From the clinical editor: This paper
      demonstrates targeting cytotoxic agents to tumor receptors using tumor-specific
      ligands. The authors describe the production of Rhodamine-labeled liposomes as
      well as doxorubicin loaded long circulating liposomes targeted to PC3 prostate
      tumor cells via PC-specific phage peptides. This approach may be especially
      relevant for advanced prostate tumors.

PMID- 20138247
TI  - A phenolic acid phenethyl urea compound inhibits lipopolysaccharide-induced
      production of nitric oxide and pro-inflammatory cytokines in cell culture.
AB  - We previously used the Curtius rearrangement to synthesize various phenolic acid
      phenethyl urea compounds from phenolic acids and demonstrated their beneficial
      anti-oxidant and anti-cancer effects. Here, we investigated the effects of one of
      these synthetic compounds, (E)-1-(3,4-dihydroxystyryl)-3-(4-hydroxyphenethyl)urea
      (DSHP-U), on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS)
      expression, and cytokine secretion in lipopolysaccharide (LPS)-stimulated RAW
      264.7 cells. DSHP-U suppressed LPS-induced NO production and iNOS expression at a
      concentration of 50 microM and inhibited LPS-induced phosphorylation of
      extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and
      p38 kinase. Inhibitors of phosphorylated (p)-ERK and p-p38, but not of p-JNK,
      reduced LPS-stimulated NO production. DSHP-U also prevented the nuclear
      translocation of the Rel A (p65) subunit and DNA-NF-kappaB binding by suppressing
      IkappaBalpha phosphorylation and by the degradation of IkappaBalpha in LPS
      stimulated cells. Furthermore, DSHP-U decreased the production of tumor necrosis
      factor-alpha, interleukin (IL)-1beta, and IL-6 in LPS-treated macrophages.
      However, the LPS-stimulated expression of LPS receptors, such as Toll-like
      receptor 4, myeloid differentiation factor-2, and CD14, was unchanged after DSHP
      U treatment at significantly high levels. Our data suggest that DSHP-U blocks NO
      and inflammatory cytokine production in LPS-stimulated macrophages and that these
      effects are mainly mediated through the inhibition of the ERK/p38- and NF-kappaB
      signaling pathways.

PMID- 20138249
TI  - [Cochlear reimplantation in the same ear: Findings, peculiarities of the surgical
      technique and complications].
AB  - INTRODUCTION: Cochlear implants are, for many reasons, expirable electronic
      devices and occasionally may have to be replaced. The surgical cochlear
      reimplantation technique is not substantially different from the initial
      implantation but does have some peculiarities. These peculiarities are analyzed
      in this paper not only from the point of view of surgical technique but also with
      respect to the complications involved and the functional auditive outcome
      obtained. OBJECTIVES: An accurate description of the surgical findings,
      peculiarities of the surgical technique and complications found during the
      process of cochlear reimplantation. An evaluation of the audiometric functional
      outcome of the reimplantation. MATERIAL AND METHOD: A descriptive retrospective
      review of 34 reimplantations in the same ear, carried out at our department
      during the period between 1993 and 2008, in 27 patients in a tertiary hospital by
      the same team of seniors surgeons. The cochlear implants replaced were 2 Ineraid
      (Smith & Nephew Richards, TN), 23 Laura (Philips Hearing Implants), 8 nucleus 24K
      (Cochlear Corp., Englewood, CO), 1 Clarion (r) (Advanced Bionics, Sylmar, CA).
      RESULTS: The rate of reimplantation in the same ear was 18.5% per patient. The
      most frequent reason in our series was internal failure of the device (14 cases).
      Other causes were substitution for a technological update (7 cases), misplacement
      of electrodes (8 cases), necrosis/infection of the skin flap with exposure of the
      implant (3 cases) and external injuries (2 cases). The most important surgical
      findings were partial mastoidectomy reossification, absence of ossification in
      the posterior tympanostomy and the permeability of the basal turn of the cochlea
      when it housed the electrodes. A complete reintroduction of the electrodes was
      achieved in 25 patients and a partial one in 2 patients. The rate of
      complications generated was similar in reimplantation and in virgin ear
      implantation, except for when the original implant was an Ineraid device.
      CONCLUSIONS: The surgical technique of reimplantation and multireimplantation
      technique has characteristic peculiarities at each step, but in general terms,
      its complexity is similar to that of implantation in virgin ears and the rate of
      complications is also similar. The introduction of the new electrodes is simple
      and complete in the immense majority of cases, given that the cochlea remains
      permeable, as long as it houses the electrodes; otherwise it tends to become
      reossified. The functional auditory outcome of the new implant is in relation
      with its capacities. If they are equal to those of the initial implant then the
      auditory outcome will be similar and if they are better, then so will the outcome
      be, with the exception of ears with long periods of auditive deprivation.

PMID- 20138250
TI  - [Neurofibromatosis type 2].
AB  - Type 2 neurofibromatosis (NF2) is an invalidating, inherited, dominant, autosomal
      disease. It is commonly confused with type 1 neurofibromatosis, although the two
      disorders are different. All subjects who inherit a mutated NF2 gene will develop
      the disease, which is characterised by the growth of schwannomas, generally
      affecting the vestibular nerve bilaterally, as well as meningiomas and other
      benign central nervous system tumours, before their third decade of life. It is
      currently possible to identify the NF2 mutation in most affected families. Up to
      about 20% of NF2 patients with no family history, apparently sporadic cases, are
      actually individuals with mosaicism for this mutation. Much of the morbidity from
      these tumours results from their treatment, which is primarily surgical. Small
      vestibular schwannomas can often be completely resected with preservation of both
      hearing and facial function. In case of large tumours it is possible to place a
      cochlear or brain stem implant during the schwannoma surgery. Age at diagnosis,
      the presence of intracranial meningiomas, and whether the patient was treated at
      a specialty centre or not, have been cited as the strongest prognostic factors.

PMID- 20138251
TI  - Inhibition of glycolysis enhances cisplatin-induced apoptosis in ovarian cancer
      cells.
AB  - OBJECTIVE: Up-regulation of glycolysis has been demonstrated in multiple tumor
      types and is believed to originate as an adaptive response to the selective
      pressure of the tumor microenvironment. We hypothesized that ovarian cancer cells
      are dependent on the glycolytic pathway for adenosine triphosphate generation and
      that this phenotype could be exploited for therapeutic intervention. STUDY
      DESIGN: Expression of glucose transporter 1 (Glut1), phosphorylated protein
      kinase B (pPKB/pAkt), and phosphorylated mammalian target of rapamycin (pmTOR)
      was assessed in ovarian carcinoma tumors and cell lines. Cells were incubated
      with 2-deoxyglucose and rapamycin; growth inhibition, viability, and mechanism of
      cell death were determined. RESULTS: Ovarian carcinoma cells overexpress Glut1,
      pAkt, and pmTOR compared with benign ovarian epithelial cells. 2-deoxyglucose and
      rapamycin markedly enhance apoptotic and nonapoptotic cell death in ovarian
      cancer cells. CONCLUSION: The glycolytic phenotype of ovarian cancer cells can be
      targeted for therapeutic intervention. Combined treatment modalities that target
      multiple cellular pathways hold promise for the treatment of chemoresistant
      ovarian cancer cells.

PMID- 20138252
TI  - Orienting and maintenance of gaze in contamination fear: Biases for disgust and
      fear cues.
AB  - The present study examines the extent to which attentional biases in
      contamination fear commonly observed in obsessive-compulsive disorder (OCD) are
      specific to disgust or fear cues, as well as the components of attention
      involved. Eye tracking was used to provide greater sensitivity and specificity
      than afforded by traditional reaction time measures of attention. Participants
      high (HCF; n = 23) and low (LCF; n = 25) in contamination fear were presented
      with disgusted, fearful, or happy faces paired with neutral faces for 3 s trials.
      Evidence of both vigilance and maintenance-based biases for threat was found. The
      high group oriented attention to fearful faces but not disgusted faces compared
      to the low group. However, the high group maintained attention on both disgusted
      and fearful expressions compared to the low group, a pattern consistent across
      the 3 s trials. The implications of these findings for conceptualizing emotional
      factors that moderate attentional biases in contamination-based OCD are
      discussed.

PMID- 20138253
TI  - Treatment of acute mania with modafinil monotherapy.

PMID- 20138254
TI  - Impact of depression and antidepressant treatment on heart rate variability: a
      review and meta-analysis.
AB  - BACKGROUND: Depression is associated with an increase in the likelihood of
      cardiac events; however, studies investigating the relationship between
      depression and heart rate variability (HRV) have generally focused on patients
      with cardiovascular disease (CVD). The objective of the current report is to
      examine with meta-analysis the impact of depression and antidepressant treatment
      on HRV in depressed patients without CVD. METHODS: Studies comparing 1) HRV in
      patients with major depressive disorder and healthy control subjects and 2) the
      HRV of patients with major depressive disorder before and after treatment were
      considered for meta-analysis. RESULTS: Meta-analyses were based on 18 articles
      that met inclusion criteria, comprising a total of 673 depressed participants and
      407 healthy comparison participants. Participants with depression had lower HRV
      (time frequency: Hedges' g = -.301, p < .001; high frequency: Hedges' g = -.293,
      p < .001; nonlinear: Hedges' g = -1.955, p = .05; Valsalva ratio: Hedges' g = 
      .712, p < .001) than healthy control subjects, and depression severity was
      negatively correlated with HRV (r = -.354, p < .001). Tricyclic medication
      decreased HRV, although serotonin reuptake inhibitors, mirtazapine, and
      nefazodone had no significant impact on HRV despite patient response to
      treatment. CONCLUSIONS: Depression without CVD is associated with reduced HRV,
      which decreases with increasing depression severity, most apparent with nonlinear
      measures of HRV. Critically, a variety of antidepressant treatments do not
      resolve these decreases despite resolution of symptoms, highlighting that
      antidepressant medications might not have HRV-mediated cardioprotective effects
      and the need to identify individuals at risk among patients in remission.

PMID- 20138255
TI  - Simulating neurocognitive aging: effects of a dopaminergic antagonist on brain
      activity during working memory.
AB  - BACKGROUND: Previous correlational studies have indirectly linked dysfunctional
      dopaminergic neurotransmission to age-related cognitive deficits and associated
      reductions in task-induced functional brain activity. METHODS: We used an
      experimental-pharmacological functional magnetic resonance imaging (fMRI)
      approach to more directly examine the role of dopamine in neurocognitive aging.
      Twenty younger and 20 healthy older adults were included. During fMRI scanning, a
      spatial working memory (SWM) task was administered under two conditions, varying
      in cognitive load. Positron emission tomography measurements with the D1 receptor
      antagonist [(11)C]SCH23390 confirmed that a given experimental dose of unlabeled
      solution occupied 50% of D1 receptors in younger adults. RESULTS: An age-related
      reduction in SWM performance was observed, and fMRI data revealed that, relative
      to younger adults under placebo conditions, elderly persons under-recruited load
      sensitive fronto-parietal regions during SWM. Critically, in younger adults, the
      D1 antagonist resulted in a similar reduction in SWM performance and fMRI
      response. CONCLUSIONS: These results suggest that depletion of dopamine, whether
      ontogenetically or pharmacologically, results in decreased SWM performance as
      well as reduced load-dependent modulation of the blood oxygen level dependent
      signal in fronto-parietal regions, possibly by decreasing the signal-to-noise
      ratio in relevant neural networks.

PMID- 20138256
TI  - Synthesis of a trigalacturonic acid analogue mimicking the expected transition
      state in the glycosidases.
AB  - A trigalacturonic acid analogue carrying a cyclohexene framework in place of the
      central pyranose ring was synthesized as a molecular probe for the mechanistic
      investigation of endo-polygalacturonase 1 (endo-PG 1). Preliminary enzymatic
      studies revealed that this analogue inhibited endo-PG 1 activity by about 30% at
      0.3mM concentration.

PMID- 20138257
TI  - A kinetic study on the chemical cleavage of nucleoside diphosphate sugars.
AB  - Nucleoside diphosphate sugars serve in essential roles in metabolic processes.
      They have, therefore, been used in mechanistic studies on glycosylation
      reactions, and their analogues have been synthesised as enzyme and receptor
      inhibitors. Despite extensive biochemical research, little is known about their
      chemical reactions. In the present work the chemical cleavage of two different
      types of nucleoside diphosphate sugars has been studied. UDP-Glc is
      phosphorylated at the anomeric carbon, whereas in ADP-Rib C-1 is unsubstituted,
      allowing hence the equilibrium between cyclic hemiacetal and acyclic carbonyl
      forms. Due to the structural difference, these substrates react via different
      pathways under slightly alkaline conditions: while UDP-Glc reacts exclusively by
      a nucleophilic attack of a glucose hydroxyl group on the diphosphate moiety, ADP
      Rib undergoes a complex reaction sequence that involves isomerisation processes
      of the acyclic ribose sugar and results in a release of ADP.

PMID- 20138258
TI  - Novel synthesis of methyl 4,6-O-benzylidenespiro[2-deoxy-alpha-D-arabino
      hexopyranoside-2,2'-imidazolidine] and its homologue and sugar-gamma-butyrolactam
      derivatives from methyl 4,6-O-benzylidene-alpha-D-arabino-hexopyranosid-2-ulose.
AB  - Novel methyl 4,6-O-benzylidenespiro[2-deoxy-alpha-D-arabino-hexopyranoside-2,2'
      imidazolidine] and its homologue methyl 4,6-O-benzylidene-3',4',5',6'-tetrahydro
      1'H-spiro[2-deoxy-alpha-D-arabino-hexopyranoside-2,2'-pyrimidine] have been
      synthesized in good yields by reaction of methyl 4,6-O-benzylidene-alpha-D
      arabino-hexopyranosid-2-ulose with 1,2-diaminoethane and 1,3-diaminopropane. The
      results are completely different from the reaction with arylamines or
      alkylamines. One-pot synthesis of novel (E)-methyl 4-[hydroxy (methoxy)methylene]
      5-oxo-1-alkyl-(4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranosido)[3,2
      b]pyrrolidines has been achieved by the reaction of alkylamines with the
      butenolide-containing sugar, derived from the aldol condensation of methyl 4,6-O
      benzylidene-alpha-D-arabino-hexopyranosid-2-ulose with diethyl malonate. These
      sugar-gamma-butyrolactam derivatives are potential GABA receptor ligands.

PMID- 20138259
TI  - Effects of the acid polysaccharide fraction isolated from a cultivated Cordyceps
      sinensis on macrophages in vitro.
AB  - The acid polysaccharide fraction (APSF) extracted from the mycelia of cultivated
      Cordyceps sinensis is water-soluble polysaccharide. In this study we evaluated
      the modulating effects of APSF on murine macrophage cell line RAW264.7.
      Phagocytotic assay by neutral red and FITC-dextran internalization showed that
      APSF stimulated the phagocytosis of macrophages. The nitrite levels in the
      culture supernatant determined using Griess reagent revealed the elevation of NO
      production after treatment with APSF. RT-PCR and immunocytochemistry assay
      indicated that APSF promoted both the mRNA and protein expressions of inducible
      nitric oxide synthase (iNOS). Furthermore, Western blotting demonstrated that NF
      kappaB levels in nucleuses increased after APSF treatment, suggesting that APSF
      probably stimulated macrophage activities by activating the IkappaB-NF-kappaB
      pathway.

PMID- 20138260
TI  - [Primary gastric CD30 (Ki-1)-positive anaplastic large cell lymphoma].

PMID- 20138261
TI  - Beyond the mental number line: A neural network model of number-space
      interactions.
AB  - It is commonly assumed that there is an interaction between the representations
      of number and space (e.g., Dehaene, Bossini, & Giraux, 1993; Walsh, 2003),
      typically ascribed to a mental number line. The exact nature of this interaction
      has remained elusive, however. Here we propose that spatial aspects are not
      inherent to number representations, but that instead spatial and numerical
      representations are separate. However, cultural factors establish ties between
      them. By extending earlier models (Gevers, Verguts, Reynvoet, Caessens, & Fias,
      2006; Verguts, Fias, & Stevens, 2005) based on this hypothesis, the authors
      present computer simulations showing that a model incorporating this idea can
      account for data from a series of studies. These results suggest that number
      space interactions are emergent properties resulting from the interaction between
      different brain areas.

PMID- 20138262
TI  - Cerebral reorganization as a function of linguistic recovery in children: An fMRI
      study.
AB  - Characterizing and mapping the relationship between neuronal reorganization and
      functional recovery are essential to the understanding of cerebral plasticity and
      the dynamic processes which occur following brain damage. The neuronal mechanisms
      underlying linguistic recovery following left hemisphere (LH) lesions are still
      unknown. Using functional magnetic resonance imaging (fMRI), we investigated
      whether the extent of brain lateralization of linguistic functioning in specific
      regions of interest (ROIs) is correlated with the level of linguistic performance
      following recovery from acquired childhood aphasia. The study focused on a rare
      group of children in whom lesions occurred after normal language acquisition, but
      prior to complete maturation of the brain. During fMRI scanning, rhyming,
      comprehension and verb generation activation tasks were monitored. The imaging
      data were evaluated with reference to linguistic performance measured
      behaviorally during imaging, as well as outside the scanner. Compared with normal
      controls, we found greater right hemisphere (RH) lateralization in patients.
      However, correlations with linguistic performance showed that increased
      proficiency in linguistic tasks was associated with greater lateralization to the
      LH. These results were replicated in a longitudinal case study of a patient
      scanned twice, 3 years apart. Additional improvement in linguistic performance of
      the patient was accompanied by increasing lateralization to the LH in the
      anterior language region. This, however, was the result of a decreased
      involvement of the RH. These findings suggest that recovery is a dynamic, ongoing
      process, which may last for years after onset. The role of each hemisphere in the
      recovery process may continuously change within the chronic stage.

PMID- 20138263
TI  - The impact of self-citation.

PMID- 20138264
TI  - Rats, dyslexia, and the magnocellular system.

PMID- 20138265
TI  - Arsenic species, AS3MT amount, and AS3MT gene expression in different brain
      regions of mouse exposed to arsenite.
AB  - Human exposure to inorganic arsenic (iAs) has been associated with cancer and
      serious injury to various internal organs, as well as peripheral neuropathy,
      endocrine disruption and diverse effects in the central nervous system (CNS).
      Using rodent models, it is possible to demonstrate As accumulation in the brain
      that leads to defects in operant learning, behavioral changes, and affect
      pituitary gonadotrophins. iAs biomethylation in the CNS is a significant process,
      yielding products that are more reactive and toxic than the parent compound. Mice
      received 2.5, 5, and 10 mg/kg/day sodium arsenite orally for 9 days. We
      investigated the distribution of iAs and its metabolites as well as the mRNA and
      protein expression of arsenic (III) methyltransferase (AS3MT), which encodes the
      key enzyme in iAs metabolism, in the cerebral cortex, hippocampus, striatum,
      mesencephalon, thalamus, cerebellum, hypothalamus, pons, medulla oblongata, and
      pituitary of mouse brain. Our findings show that methylated As metabolites are
      present in all brain regions studied suggesting that AS3MT is ubiquitously
      expressed in the brain and it is not inducible by dose of arsenite. There is also
      a dose-related accumulation of As species in all brain regions, with the highest
      accumulation observed in the pituitary. The higher distribution of arsenicals in
      pituitary can help to explain the neuroendocrine effects associated with iAs
      exposure.

PMID- 20138266
TI  - Relationship of reactive oxygen species levels in day 3 culture media to the
      outcome of in vitro fertilization/intracytoplasmic sperm injection cycles.
AB  - OBJECTIVE: To examine the relationship of early human embryonic development
      parameters to day 3 reactive oxygen species (D-3 ROS) levels in culture media.
      DESIGN: Prospective study. SETTING: Tertiary care hospital. PATIENT(S): Patients
      were undergoing IVF (n=92; 36 with intracytoplasmic sperm injection [ICSI]).
      INTERVENTION(S): The D-3 ROS levels in sample and control of each embryo culture
      dish were measured by the chemiluminescence method using a luminol probe. MAIN
      OUTCOME MEASURE(S): Embryo quality (days 3 and 5) and pregnancy rates (PR).
      RESULT(S): The D-3 ROS level was significantly lower in pregnant cycles 26.8+/
      13.9*10(6) cpm (counted photon per minute) versus nonpregnant cycles 66.4+/
      39.4*10(6) cpm. This relationship was maintained when the cycles were stratified
      to conventional IVF (27.1+/-14.95 vs. 67.0+/-39.9*10(6) cpm) or ICSI (25.6+/
      12.75 vs. 65.5+/-39.7*10(6) cpm). After controlling for all variables, D-3 ROS
      levels were negatively correlated with blastocyst development rate as well as PR.
      Odds ratio (OR) (95% confidence interval [CI]) of clinical pregnancy
      corresponding to a 10*10(6) cpm increase in D-3 ROS was 0.47 (0.30-0.74) for ICSI
      and 0.56 (0.37-0.85) for IVF. CONCLUSION(S): During extended in vitro culture,
      ROS generated in culture media by day 3 may be an important biochemical marker
      for blastulation. An increase of 10 units in D-3 ROS may decrease the clinical
      pregnancy by 41%.

PMID- 20138267
TI  - Serum antimullerian hormone concentrations on day 3 of the in vitro fertilization
      stimulation cycle are predictive of the fertilization, implantation, and
      pregnancy in polycystic ovary syndrome patients undergoing assisted reproduction.
AB  - OBJECTIVE: To determine the possible relationship between serum antimullerian
      hormone (AMH) concentrations on day 3 and controlled ovarian stimulation and
      reproductive outcomes in women with polycystic ovary syndrome. DESIGN:
      Prospective, clinical trial. SETTING: University hospital. PATIENT(S): Sixty
      women with PCOS. INTERVENTION(S): Serum concentrations of AMH measured on cycle
      day 3. MAIN OUTCOME MEASURE(S): Clinic pregnancy rate (CPR), implantation rate
      (IR), and fertilization rate (FR). RESULT(S): The CPR, IR, and FR were markedly
      different among the day-3 serum AMH groups (low, moderate, and high AMH groups).
      The CPR were 33.3, 46.1, and 60.0, respectively, in the low, moderate, and high
      serum AMH groups on day 3. The embryo IR were 18.6, 26.7, and 36.3, respectively.
      The FR were 54, 68, and 79, respectively. An AMH level>=3.01 ng/mL was shown to
      predict FR with a sensitivity of 86.4% and specificity of 75%. An AMH level>=3.2
      ng/mL was shown to predict IR and CPR with sensitivity and specificity of 72.1%
      and 72.7%, and 75.6% and 77.3%, respectively. CONCLUSION(S): On day 3 of the in
      vitro fertilization stimulation cycle, serum concentrations of AMH can be used as
      a marker for ovarian response as well as reproductive outcome in assisted
      reproductive cycles of PCOS patients.

PMID- 20138268
TI  - Arguments for a left lateral predisposition of endometrioma.

PMID- 20138269
TI  - An ongoing pregnancy from two waves of follicles developing during a long
      follicular phase of the same cycle.
AB  - OBJECTIVE: To report an ongoing pregnancy after in vitro fertilization (IVF) with
      ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist that
      resulted in two waves of follicular growth. DESIGN: Case report. SETTING:
      University of Toronto affiliated infertility clinic. PATIENT(S): A 33-year-old
      woman with a 3-year history of secondary infertility. INTERVENTION(S): In vitro
      fertilization and embryo transfer. MAIN OUTCOME MEASURE(S): Ongoing pregnancy.
      RESULT(S): This patient successfully conceived after the GnRH antagonist-induced
      demise of the first cohort of follicles and the emergence of a second wave of
      follicles followed by oocyte retrieval on cycle day 30 and fresh embryo transfer.
      CONCLUSION(S): This case report is consistent with previous observations of
      multiple waves of follicle recruitment and growth per cycle. The window of
      implantation may not be adversely affected by prolonged or even variable estrogen
      exposure in the follicular phase of the cycle.

PMID- 20138270
TI  - Selective insulin-like growth factor-I antagonist inhibits mouse embryo
      development in a dose-dependent manner.
AB  - OBJECTIVE: To study the role of a synthetic insulin-like growth factor-I receptor
      (IGF-IR) antagonist, picropodophyllin, for mouse preimplantation embryo
      development in vivo and in vitro. DESIGN: In vitro and in vivo study. SETTING:
      Hospital-based research unit. ANIMALS: FVB/N mice and mouse embryos.
      INTERVENTION(S): The effect of picropodophyllin in mouse embryo development in
      vivo and in vitro, immunohistochemistry, ELISA, polymerase chain reaction. MAIN
      OUTCOME MEASURE(S): Embryo development, presence of IGF-IR, messenger RNA
      expression, IGF-I synthesis. RESULT(S): The effect of picropodophyllin on embryo
      development in vitro and in vivo was not reversible. Mice treated with
      picropodophyllin 1 to 3 days after mating had a reduced number of blastocysts,
      40.5% versus 78.8%, and a higher number of embryos with delayed development,
      48.6% versus 11.5%. Insulin-like growth factor-IR protein is present in both
      phosphorylated and nonphosphorylated form at all stages of embryo development.
      The relative IGF-IR messenger RNA expression was highest in the oocyte and
      reduced during development to blastocyst stage. Insulin-like growth factor-I in
      culture media was reduced after picropodophyllin treatment. CONCLUSION(S): We
      conclude that IGF-I has an important role in normal mouse embryo development and
      that its receptor plays an essential role in the embryonic genome activation
      process.

PMID- 20138271
TI  - Genital schistosomiasis as a cause of female sterility and acute abdomen.
AB  - OBJECTIVE: To report the case of a Nigerian patient who suffered from sterility
      and underwent abdominal laparotomy to remove an adnexal tumor. Histologic
      analysis revealed Schistosoma haematobium ova. DESIGN: Case report. SETTING:
      Multidisciplinary group practice and teaching hospital. PATIENTS: One patient who
      underwent an abdominal laparotomy to remove an adnexal tumor. INTERVENTION(S): In
      vitro fertilization and adnexal tumor resection via laparotomy. MAIN OUTCOME
      MEASURE(S): Treatment of the adnexal tumor affecting the reproductive health.
      RESULT(S): Histologic analysis performed on the tissue removed at surgery
      revealed fibrous patches around aggregates of calcified Schistosoma haematobium
      eggs in the fallopian tube wall. CONCLUSION(S): Schistosomiasis needs to be
      considered as a differential diagnosis of female infertility and sterility.

PMID- 20138272
TI  - Storage of human oocytes in the vapor phase of nitrogen.
AB  - OBJECTIVE: To evaluate the effectiveness of long-term vapor-phase nitrogen
      storage of vitrified human oocytes as a strategy for preventing the risk of cross
      contamination due to direct contact with the liquid nitrogen (LN). DESIGN:
      Prospective randomized study. SETTING: Private infertility center, IVI, Valencia.
      PATIENT(S): Oocyte donors (n = 44) and recipients (n = 46). INTERVENTION(S):
      Vitrification by the Cryotop method. Storage of vitrified oocytes in a vapor
      phase nitrogen storage freezer and a traditional LN storage tank. Donation of the
      surviving oocytes and evaluation of fertilization, embryo development, and
      clinical results. MAIN OUTCOME MEASURE(S): Survival, fertilization, and cleavage
      rates. Embryo quality and clinical outcome. RESULT(S): Survival was 95.3% (vapor
      phase nitrogen) and 94.5% (LN). Fertilization rates (73.1% and 71.7%) or cleavage
      on day 2 (95.6% and 94.7%), day 3 (84.5% and 79.9%), and blastocyst formation
      (54.7% and 53.9%) were similar between vapor-phase nitrogen and LN. Implantation,
      clinical, and ongoing pregnancy rates were similar for vapor-phase nitrogen
      (40.5%, 58.1%, and 48.8%, respectively) and LN groups (33.7%, 53.3%, and 46.6%,
      respectively). CONCLUSION(S): The vapor-phase nitrogen system permits the storage
      of oocytes vitrified, maintaining their potential to develop into competent
      embryos in a similar manner as those stored in a traditional LN freezer. This
      approach represents a practical alternative that prevents cross-contamination
      during the storage of vitrified samples.

PMID- 20138274
TI  - The issue of reinfibulation.
AB  - Reinfibulation is resuturing after delivery or gynecological procedures of the
      incised scar tissue resulting from infibulation. Despite the global fight against
      female genital mutilation/cutting (FGM/C), reinfibulation of previously mutilated
      or circumcised women is still performed in various countries around the world. A
      good estimate of the prevalence of reinfibulation is difficult to obtain, but it
      can be inferred that 6.5-10.4million women are likely to have been reinfibulated
      worldwide. Women who undergo reinfibulation have little influence on the decision
      making and are usually persuaded by the midwife or birth attendant to undergo the
      procedure immediately following labor or gynecological operation. Although
      medicalization of reinfibulation may reduce its immediate risks, it has no effect
      on the incidence of long-term risks. Reinfibulation is performed mainly for the
      financial benefit of the operator, and cultural values that have been perpetuated
      for generations. Reinfibulation has no benefits and is associated with
      complications for the woman and the unborn child. Its medicalization violates the
      medical code of ethics and should be abandoned. International and national
      efforts should be combined to eradicate this practice.

PMID- 20138275
TI  - Providing culturally appropriate care: a literature review.
AB  - OBJECTIVES: As part of a study that explored how midwives incorporate cultural
      sensitivity, into their practice, the literature was reviewed to ascertain how
      the concept of culture has been, defined and what recommendations have been made
      as to how to provide culturally appropriate care, to individuals from Indigenous
      and/or ethnic minority backgrounds. DESIGN: A systematic review of the literature
      was undertaken. DATA SOURCES: Electronic databases including Medline, Cinahl,
      Socio-file and Expanded Academic Index, were accessed. REVIEW METHODS: Several
      key search terms were used for example, midwife, midwives, midwifery, nurse,
      nurses, nursing, culture or cultural, diversity, sensitivity, competency and
      empowerment. The, results relating to midwifery were few; therefore 'nursing' was
      included which increased the amount, of material. References that were deemed
      useful from bibliographies of relevant texts and journal, articles were included.
      The inclusion criteria were articles that provided information about culture,
      and/or the culturally appropriate care of individuals from Indigenous and/or
      ethnically, culturally and, linguistically diverse backgrounds. Materials
      reviewed for this paper satisfied the inclusion criteria. RESULTS: There are two
      main approaches to culture; the first focuses on the cognitive aspects of
      culture, the 'values, beliefs and traditions' of a particular group, identified
      by language or location such as, 'Chinese women' or 'Arabic speaking women'. This
      approach views culture as static and unchanging, and fails to account for
      diversity within groups. The second approach incorporates culture within a wider,
      structural framework, focusing on social position to explain health status rather
      than on individual behaviours and beliefs. It includes perspectives on the impact
      of the colonial process on the ongoing relationships of Indigenous and non
      Indigenous people and how this affects health and health care. CONCLUSION: Most
      of the literature focuses on the cognitive aspects of culture and recommends
      learning about the culture of specific groups which is presumed to apply to
      everyone. This generic approach can, lead to stereotyping and a failure to
      identify the needs of the individual receiving care. The concept of, cultural
      safety derived from the second approach to culture and practice has potential but
      evidence to show how it is being incorporated into practice is lacking and health
      professionals appear to be unclear about its meaning.

PMID- 20138276
TI  - Gender specific variations in the description, intensity and location of angina
      pectoris: a cross-sectional study.
AB  - BACKGROUND: Some research suggests that men and women may experience Angina
      Pectoris (AP) differently. More research is needed to characterize AP symptoms by
      gender and to familiarize health care providers with them, to enable proper
      education, diagnostic evaluation and timely management. OBJECTIVE: This study
      examines gender differences in the description, intensity and location of AP in
      patients with CHD. DESIGN: A cross-sectional study was performed to compare AP
      patients according to gender. SETTINGS: This study was performed on patients
      residing in Tehran, who were being treated in a hospital and were admitted to
      cardiac units. PARTICIPANTS: Five hundred patients with AP were selected. The
      participants were patients with AP who were diagnosed with CHD based on
      documented results from an angiography. METHOD: Outpatients who were admitted to
      the cardiac units were screened. Informed consent was obtained from all study
      participants, who then completed the Iranian version of the AP characteristics
      questionnaire. RESULTS: Women were significantly more likely to feel pain in the
      left arm and hand, odds ratio 1.5 (95% CI=1.0-2.1, P=0.04), left scapula, odds
      ratio 2.3 (95% CI=1.6-3.5, P<0.001), and neck, odds ratio 2.8 (95% CI=1.9-4.1,
      P<0.0001), while controlling for demographic and clinical factors. Women were
      significantly more likely to choose the possible pain descriptors for describing
      their AP and reported significantly greater intensity than men for all the pain
      descriptors. Significantly higher scores for sensory, affective, total and NRS
      (Numeric Rating Scale) scores were observed in women (P<0.001). Multiple linear
      regression analyses revealed that gender remained a statistically significant
      predictor of pain scores and NRS, while controlling for demographic and clinical
      factors. CONCLUSION: Women and men differ with respect to description, intensity
      and location of AP. Educating the general public and informing health care
      providers about gender variation in AP may help to decrease delays in seeking
      medical care.

PMID- 20138277
TI  - Predictors of adjustment to nursing home life of elderly residents: a cross
      sectional survey.
AB  - BACKGROUND: Adjustment to a nursing home by elderly residents is an issue in
      transitional care in nursing homes. Although research on relocation adjustment
      has been conducted in many countries, adjustment has generally been measured with
      life satisfaction scales, assuming equivalence between life satisfaction and
      successful adjustment. Research has not been reported on adjustment to relocation
      using an adjustment scale. OBJECTIVES: To identify predictors of nursing home
      life adjustment. DESIGN: Descriptive study with cross-sectional surveys.
      PARTICIPANTS AND SETTING: One hundred fifty-six residents from seven nursing
      homes completely subsidized by the South Korea government. METHODS: A structured
      questionnaire about resident characteristics, relocation characteristics, social
      support and general facility satisfaction was administered. The facility
      characteristics were obtained from the facility records. A scale of nursing home
      adjustment was also used during one-on-one interviews. Multiple regression was
      used to identify predictors of adjustment to the nursing home life for elderly
      residents. RESULTS: The predictors of nursing home adjustment were self-efficacy,
      self-reported health, preconception about nursing homes, emotional support from
      staff and other residents, family satisfaction and general satisfaction with the
      facility. The total explained variance for this model was 60.6%. CONCLUSIONS:
      Nursing home staff should consider the following four factors in assisting the
      elderly achieve successful adjustment to a nursing home: residents, relocation,
      social support and facilities. Social support inside the facility should be
      fostered to improve nursing home adjustment. Further studies are needed to
      explore adjustment using a nursing home adjustment scale.

PMID- 20138278
TI  - Job demands-resources, burnout and intention to leave the nursing profession: a
      questionnaire survey.
AB  - OBJECTIVES: The aims of the paper are to examine the role of burnout in the
      relationship between stress factors related to nurses' work and social
      environment and intention to leave the profession and to investigate the nature
      of the relationship between burnout and intention to leave the nursing
      profession. BACKGROUND: A postulate of the job demands-resources model is that
      two distinct yet related processes contribute to the development of burnout. The
      energetic process originates from demands and is mainly centered on emotional
      exhaustion; the motivational process originates from resources and is mainly
      centered on depersonalization. Moreover, we postulated that the two components of
      burnout are linked indirectly to intention to leave the profession via
      psychosomatic complaints, associated with the energetic process, and via
      professional commitment, associated with the motivational process. METHOD: The
      research model was tested on cross-sectional data collected in 2005 from 1636
      registered nurses working in hospitals who responded to a self-administrated
      questionnaire. RESULTS: Demands are the most important determinants of emotional
      exhaustion and indirectly induce depersonalization via emotional exhaustion,
      whereas resources mainly predict depersonalization. Moreover, emotional
      exhaustion and depersonalization are linked to psychosomatic complaints and
      professional commitment, which are in turn associated with intention to leave the
      profession. CONCLUSION: The results suggest that a dual strategy is needed in
      order to retain nurses within the profession: a decrease in job demands, coupled
      with an increase in available job resources. In particular, nurses' tasks and
      role should be restructured to reduce work overload and increase the meaning of
      their work.

PMID- 20138279
TI  - Reduced LDL-cholesterol levels in patients with coronary artery disease are
      paralleled by improved endothelial function: An observational study in patients
      from 2003 and 2007.
AB  - OBJECTIVE: Recent guidelines recommend more aggressive lipid-lowering in
      secondary prevention protocols. We examined whether this resulted in improved
      endothelial function. METHODS: We studied saphenous vein specimens of patients
      undergoing surgical coronary revascularisation in 2007 and compared results with
      those of patients examined in 2003. Endothelium-dependent vasodilation was
      assessed by relaxation to calcium ionophore A23187, and vascular superoxide
      production by lucigenin enhanced chemiluminescence. RESULTS: Statin dose
      increased from 26+/-16 mg/d in 2003 to 37+/-17 mg/d in 2007 (P<0.001), and total
      (4.0+/-0.9 mmol/L vs 4.8+/-1.0 mmol/L) and LDL-cholesterol levels (2.0+/-0.7
      mmol/L vs 3.0+/-0.9 mmol/L) were lower in 2007 compared to 2003 (P<0.001; n=90
      each). Endothelium-dependent vasodilation was greater in 2007 (44+/-15%) compared
      to 2003 (28+/-12%; n=36 each; P<0.001). Vascular superoxide derived from
      endothelial NO synthase (eNOS) was lower in 2007 than in 2003 (reduction by NG
      nitro-L-arginine-methyl ester, 0.29+/-0.21 nmol/(mg min) vs 0.09+/-0.20 nmol/(mg
      min); P=0.002). In linear regression analysis, LDL-cholesterol levels have been
      shown to be the major determinant of endothelial function in the combined 2003
      and 2007 cohort. CONCLUSION: Intensive lipid-lowering is associated with improved
      endothelial function and reduced superoxide production from eNOS. Further
      improvement in vascular function could be achieved by targeting other sources of
      superoxide including xanthine oxidase.

PMID- 20138280
TI  - The epidemiology of subclavian stenosis and its association with markers of
      subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: Recent studies indicate that subclavian stenosis (SS), diagnosed by a
      large systolic blood pressure difference (SBPD) between the right and left
      brachial arteries, is associated with cardiovascular disease (CVD) risk factors
      and outcomes. We sought to describe the epidemiology of SS and determine its
      association with markers of subclinical CVD in the baseline cohort of the Multi
      Ethnic Study of Atherosclerosis. METHODS: We defined SS by an absolute SBPD>or=15
      mmHg. Peripheral artery disease (PAD) was defined by an ankle-brachial
      index<or=0.90. The coronary artery calcium score (CAC) and the common carotid
      artery intima-media thickness (CCA-IMT) were measured by computed tomography and
      B-mode ultrasound, respectively. Odds ratios for the associations of SS with risk
      factors and subclinical disease were estimated using logistic regression.
      RESULTS: Of 6743 subjects studied, 307 participants (4.6%) had SS, with a higher
      prevalence in women (5.1%) than men (3.9%), and in African Americans (7.4%) and
      non-Hispanic whites (5.1%) than Hispanic (1.9%) or Chinese (1.0%) participants
      (p<0.01). In a model including age, gender, ethnicity, traditional and novel CVD
      risk factors, significant associations with SS were observed for C-reactive
      protein (highest vs. three lower quartiles: OR=1.41; 95%CI: 1.06-1.87) and
      brachial artery pulse pressure (OR=1.12/10 mmHg; 95%CI: 1.03-1.21). Adjusted for
      age, gender, ethnicity, traditional and novel CVD risk factors, SS was
      significantly associated with PAD (OR=2.35; 1.55-3.56), with CCA-IMT (highest vs.
      the lower three quartiles: OR=1.32; 1.00-1.75), and high CAC (score>100 vs.
      score=0; OR=1.43; 1.03-2.01). CONCLUSIONS: The subclavian stenosis is positively
      associated with other markers of subclinical atherosclerosis.

PMID- 20138281
TI  - ABC transporters, atherosclerosis and inflammation.
AB  - Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary
      arteries and lead to myocardial infarction. This chronic disease is a major and
      expensive health burden. However, the body is able to mobilize and excrete
      cholesterol and other lipids, thus preventing atherosclerosis by a process termed
      reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been
      gained by the study of two rare syndromes caused by the mutation of ABC
      transporter loci. In Tangier disease, loss of ABCA1 prevents cells from exporting
      cholesterol and phospholipid, thus resulting in the build-up of cholesterol in
      the peripheral tissues and a loss of circulating HDL. Consistent with HDL being
      an athero-protective particle, Tangier patients are more prone to develop
      atherosclerosis. Likewise, sitosterolemia is another inherited syndrome
      associated with premature atherosclerosis. Here mutations in either the ABCG5 or
      G8 loci, prevents hepatocytes and enterocytes from excreting cholesterol and
      plant sterols, including sitosterol, into the bile and intestinal lumen. Thus,
      ABCG5 and G8, which from a heterodimer, constitute a transporter that excretes
      cholesterol and dietary sterols back into the gut, while ABCA1 functions to
      export excess cell cholesterol and phospholipid during the biogenesis of HDL.
      Interestingly, a third protein, ABCG1, that has been shown to have anti
      atherosclerotic activity in mice, may also act to transfer cholesterol to mature
      HDL particles. Here we review the relationship between the lipid transport
      activities of these proteins and their anti-atherosclerotic effect, particularly
      how they may reduce inflammatory signaling pathways. Of particular interest are
      recent reports that indicate both ABCA1 and ABCG1 modulate cell surface
      cholesterol levels and inhibit its partitioning into lipid rafts. Given lipid
      rafts may provide platforms for innate immune receptors to respond to
      inflammatory signals, it follows that loss of ABCA1 and ABCG1 by increasing raft
      content will increase signaling through these receptors, as has been
      experimentally demonstrated. Moreover, additional reports indicate ABCA1, and
      possibly SR-BI, another HDL receptor, may directly act as anti-inflammatory
      receptors independent of their lipid transport activities. Finally, we give an
      update on the progress and pitfalls of therapeutic approaches that seek to
      stimulate the flux of lipids through the RCT pathway.

PMID- 20138282
TI  - Relationship between Mediterranean Diet Score and atherothrombotic risk: findings
      from the Third National Health and Nutrition Examination Survey (NHANES III),
      1988-1994.
AB  - BACKGROUND: Mediterranean diet has been promoted as the preferred dietary model
      for cardiovascular disease prevention in the United States. OBJECTIVE: We sought
      to evaluate the degree to which the Mediterranean diet is associated with reduced
      levels of atherothrombotic biomarkers in a population-based sample in the U.S.
      DESIGN: Data from 13,197 adults between the ages of 18 and 90 were collected and
      atherothrombotic risk factors assessed as part of the NHANES III, 1988-1994.
      Adherence to the Mediterranean diet was evaluated using food frequency
      questionnaires, supplemented by the 24-h dietary recall data, to develop
      Mediterranean Diet Scores (MedDietScore) that were analyzed in tertiles. The
      cross-sectional relationship of MedDietScore to atherothrombotic factors were
      analyzed using multiple variable regression analysis adjusted for complex
      sampling design using SUDAAN. RESULTS: The components of the Mediterranean diet
      and the dietary pattern's associations with atherothrombotic risk factors
      differed by age and gender. For men <45 years of age as MedDietScore increased:
      total cholesterol/HDL cholesterol (TC/HDL) ratio (p=0.0390), serum insulin
      (p=0.0414), and white blood cell (WBC) (p=0.0246) decreased. For men>or=45 years
      as MedDietScore increased: TC/HDL ratio (p=0.0008), Hemoglobin A1c (HgbA1c)
      (p=0.0001), HOMA index (p=0.0486), C-reactive protein (p=0.0034), fibrinogen
      (p=0.0028) decreased and HDL cholesterol (HDL-c) levels (p<0.0001) increased. For
      pre-menopausal women, as MedDietScore increased: TC/HDL ratio (p<0.0001), non-HDL
      cholesterol (p=0.0012), apolipoprotein B (p=0.0112), HgbA1c (p=0.0001), decreased
      and HDL-c levels (p<0.0001) increased. For post-menopausal women, as MedDietScore
      increased: TC/HDL ratio (p=0.0005), Triglycerides (p<0.0001), serum insulin
      (p=0.0062), HOMA index (p=0.0063) and Homocysteine (Hcy) (0.0046) levels
      decreased and HDL-c levels (p=0.0005) increased. CONCLUSIONS: Mediterranean diet
      appears to be associated with selective measures of cardioprotective lipid
      profiles, glucose metabolism, and inflammation and coagulation levels.

PMID- 20138283
TI  - Quantitative determination of triclocarban in wastewater effluent by stir bar
      sorptive extraction and liquid desorption-liquid chromatography-tandem mass
      spectrometry.
AB  - Triclocarban is an antimicrobial and antibacterial agent found in personal care
      products and subsequently is a prevalent wastewater contaminant. A quantitative
      method was developed for the analysis of triclocarban in wastewater effluents
      using stir bar sorptive extraction-liquid desorption (SBSE-LD) followed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) by means of an electrospray
      interface. A stir bar coated with polydimethylsiloxane (PDMS) is placed within a
      vial containing wastewater effluent and is stirred for an hour at room
      temperature. The PDMS stir bar is then placed in a LC vial containing methanol
      and is desorbed in a sonicator bath. The methanol is evaporated to dryness and
      reconstituted in 75% methanol. Spike and recovery experiments in groundwater that
      did not contain native concentrations of triclocarban were performed at 0.5
      microg/L and were 93+/-8%. Recoveries in wastewater effluent that were corrected
      for the background levels of triclocarban were 92+/-2% and 96+/-5%, respectively,
      when spiked with 0.5 and 5 microg/L of triclocarban. The precision of the method
      as indicated by the relative standard error was 2%. The limit of quantitation was
      10 ng/L. The SBSE-LD-LC/MS/MS method was applied to wastewater effluent samples
      collected from northeast Ohio. Triclocarban was quantitated in all five effluent
      samples, and its concentration ranged from 50 to 330 ng/L. The described method
      demonstrates a simple, green, low-sample volume, yet, sensitive method to measure
      triclocarban in aqueous matrices.

PMID- 20138284
TI  - The non-modulated transfer of total effluent for serially coupled columns in gas
      chromatography.
AB  - The non-modulated transfer (NMT) of the total effluent of the separation of
      polychlorinated biphenyls (PCBs) on two columns coupled in series has been
      studied. A non-polar poly(5%-phenyl-95%-methyl)siloxane column (40 m x 100 microm
      x 0.1 microm) and a polar 70%-cyanopropyl-polysilphenylene-siloxane column (4 m x
      0.1 mm x 0.1 microm) were used as (1)D and (2)D columns, respectively. The
      effluents from both the (1)D column and the (1)D+(2)D column series were
      monitored independently by two FIDs. Data from the (1)D and (1)D+(2)D integration
      reports were used to evaluate the NMT experiment. (1)D retention times,
      t(R,i,D1), were directly accessible from (1)D integration report while (2)D
      retention times, t(R,i,B), were calculated for all corresponding peak pairs from
      (1)D and (1)D+(2)D integration reports as a difference t(R,i,D2)=t(R,i,D1+D2)
      t(R,i,D1). Search for corresponding peaks of PCB congeners in the (1)D and
      (1)D+(2)D chromatograms is elucidated in detail on standard PCB samples and on
      PCB congeners present in the technical formulation Arochlor 1242. Both retention
      times (t(R,i,D1) and t(R,i,D2)) as well as peak widths at half height (w(h,i))
      and peak heights (h(i)) obtained from integration reports were used to construct
      2D and 3D images for PCB NMT separations on serially coupled columns. The
      performance of the NMT procedure is illustrated by the separation of (i) standard
      PCB solutions, (ii) a mixture of the 209 PCBs, and (iii) a mixture of Arochlor
      1242 and hydrocarbons on the DB-5+BPX-70 column series.

PMID- 20138285
TI  - On-line continuous flow ultrasonic extraction coupled with high performance
      liquid chromatographic separation for determination of the flavonoids from root
      of Scutellaria baicalensis Georgi.
AB  - An on-line method, based on coupling dynamic ultrasonic extraction (DUE),
      continuously sampling the suspension of sample and solvent, high performance
      liquid chromatographic separation with diode array detection, has been developed
      for the determination of the flavonoids, including baicalin, baicalein and
      wogonin, from the root of Scutellaria baicalensis Georgi. Variables influencing
      the DUE were evaluated by orthogonal test. The extraction yields of baicalin,
      baicalein and wogonin in the roots of S. baicalensis Georgi obtained from five
      different cultivated areas are 73.8-131.5 microg mg(-1) (RSD< or =6.24%), 6.8
      15.9 microg mg(-1) (RSD< or =5.36%) and 4.4-14.3 microg mg(-1) (RSD< or =5.30%),
      respectively. The limits of detection for baicalin, baicalein and wogonin are
      0.30, 0.37 and 0.41 microg mL(-1), respectively. Linearity is from 0.55 to 109
      microg mL(-1) for baicalin, from 0.51 to 105 microg mL(-1) for baicalein and from
      0.53 to 102 microg mL(-1) for wogonin. Compared with off-line continuous flow
      DUE, the proposed method would be more convenient for the determination of the
      analytes and the rapid optimization of the extraction process. The extraction
      yields of flavonoids obtained by the proposed method are comparable with those
      obtained by dynamic microwave assisted extraction, static ultrasonic extraction
      and reflux extraction. The result indicated that the proposed method is suitable
      to determine the active components in Chinese herbal medicine.

PMID- 20138286
TI  - Measurement of retention in comprehensive two-dimensional gas chromatography
      using flow modulation with methane dopant.
AB  - Flow modulation of methane-doped carrier gas is used to visualize the second
      dimension hold-up time in GC x GC continuously throughout the run. This provides
      an internal reference of hold-up time and presents a straightforward means of
      examining retention in each dimension of GC x GC. Retention factors on similar
      and dissimilar column pairs are examined. Stationary phase bleed is shown to be
      retained by the second dimension column.

PMID- 20138287
TI  - Determination of triazine herbicides using membrane-protected carbon nanotubes
      solid phase membrane tip extraction prior to micro-liquid chromatography.
AB  - A novel microextraction technique termed solid phase membrane tip extraction
      (SPMTE) was developed. Selected triazine herbicides were employed as model
      compounds to evaluate the extraction performance and multiwall carbon nanotubes
      (MWCNTs) were used as the adsorbent enclosed in SPMTE device. The SPMTE procedure
      was performed in semi-automated dynamic mode and several important extraction
      parameters were comprehensively optimized. Under the optimum extraction
      conditions, the method showed good linearity in the range of 1-100 microg/L,
      acceptable reproducibility (RSD 6-8%, n=5), low limits of detection (0.2-0.5
      microg/L), and satisfactory relative recoveries (95-101%). The SPMTE device could
      be regenerated and reused up to 15 analyses with no analyte carry-over effects
      observed. Comparison was made with commercially available solid phase extraction
      molecular imprinted polymer cartridge (SPE-MIP) for triazine herbicides as the
      reference method. The new developed method showed comparable or even better
      results against reference method and is a simple, feasible, and cost effective
      microextraction technique.

PMID- 20138288
TI  - Determination of fragrance allergens in indoor air by active sampling followed by
      ultrasound-assisted solvent extraction and gas chromatography-mass spectrometry.
AB  - Fragrances are ubiquitous pollutants in the environment, present in the most of
      household products, air fresheners, insecticides and cosmetics. Commercial
      perfumes may contain hundreds of individual fragrance chemicals. In addition to
      the widespread use and exposure to fragranced products, many of the raw fragrance
      materials have limited available health and safety data. Because of their nature
      as artificial fragrances, inhalation should be considered as an important
      exposure pathway, especially in indoor environments. In this work, a very simple,
      fast, and sensitive methodology for the analysis of 24 fragrance allergens in
      indoor air is presented. Considered compounds include those regulated by the EU
      Directive, excluding limonene; methyl eugenol was also included due to its
      toxicity. The proposed methodology is based on the use of a very low amount of
      adsorbent to retain the target compounds, and the rapid ultrasound-assisted
      solvent extraction (UAE) using a very low volume of solvent which avoids further
      extract concentration. Quantification was performed by gas chromatography coupled
      to mass spectrometry (GC-MS). The influence of main factors involved in the UAE
      step (type of adsorbent and solvent, solvent volume and extraction time) was
      studied using an experimental design approach to account for possible factor
      interactions. Using the optimized procedure, 0.2 m(-3) air are sampled, analytes
      are retained on 25 mg Florisil, from which they are extracted by UAE (5 min) with
      2 mL ethyl acetate. Linearity was demonstrated in a wide concentration range.
      Efficiency of the total sampling-extraction process was studied at several
      concentration levels (1, 5 and 125 microg m(-3)), obtaining quantitative
      recoveries, and good precision (RSD<10%). Method detection limits were < or =0.6
      microg m(-3). Finally, the proposed method was applied to real samples collected
      in indoor environments in which several of the target compounds were determined.

PMID- 20138289
TI  - Comparison of two different isolation methods of benzimidazoles and their
      metabolites in the bovine liver by solid-phase extraction and liquid
      chromatography-diode array detection.
AB  - A new analytical method that uses high performance liquid chromatography-diode
      array detector (HPLC-DAD) was developed for the analysis of 14 benzimidazoles
      residues, including metabolites, in bovine liver. Samples were extracted using
      two different extraction procedures: with phosphate buffer after enzymatic
      hydrolysis (method A) or using organic solvent, i.e. acetonitrile (method B).
      Then, samples were purified on a strong cation exchange (SCX) cartridge and
      analyzed in HPLC/DAD. The recovery percentages, obtained spiking the matrix
      (liver) at concentrations of 500 and 100 microg kg(-1) with a standard mixture of
      benzimidazoles, were in the range 6-101% and 80-102% for methods A and B,
      respectively. The repeatability of the methods was assessed in all cases by the %
      of correlation value (CV) that was lower than 19%. The limits of quantification
      (LOQs) in the matrix for methods A and B were in the range 40-60 and 20-50 microg
      kg(-1), respectively. The best of the two methods, method B, was used for the
      analysis of 10 bovine liver samples.

PMID- 20138290
TI  - Hybrid photosynthetic materials derived from microalgae Cyanidium caldarium
      encapsulated within silica gel.
AB  - Cyanidium caldarium (Tilden) Geitler SAG 16.91 has been encapsulated within a
      porous silica host structure to target novel photosynthetic hybrid materials
      suitable for use in solar cells or CO(2) fixation. C. caldarium cells are both
      thermophilic and acidophilic; on account of these tolerances the hybrid materials
      could be employed in more extreme heat conditions. TEM highlights that the
      external cell membrane can remain intact after encapsulation. The images reveal
      an alignment of silica gel around the external membrane of the cell, providing
      evidence that the cell wall acts as both a nucleation and polymerisation site for
      silica species and that the silica scaffold formed by the aggregation of
      colloidal particles, generates a porosity that can facilitate the transport of
      nutrients towards the cell. Epifluorescence microscopy and UV-visible
      spectroscopy have revealed the preservation of photosynthetic apparatus post
      immobilisation. Productivity studies showed how the presence of silica
      nanoparticles within the matrix can adversely interact with the exterior cellular
      structures preventing the production of oxygen through photosynthesis.

PMID- 20138291
TI  - Aggregation of zinc oxide nanoparticles: from non-aqueous dispersions to
      composites used as photoactive layers in hybrid solar cells.
AB  - Hybrid solar cells are third-generation solar cells that are colloidal in nature.
      The composites used as photoactive layers within hybrid solar cells comprise
      conjugated polymers and inorganic semiconductor nanoparticles (e.g., nanocrystals
      and nanorods). The composites are usually prepared by spin casting non-aqueous
      dispersions consisting of polymer, nanoparticles and a co-solvent blend. The
      factors governing colloidal stability of the dispersions used for composite
      preparation have not been reported in detail. Here, the factors governing the
      stability of non-aqueous ZnO nanocrystal and nanorod dispersions as well as the
      relationship between dispersion stability and the extents of nanoparticle
      aggregation within model composites are studied. The polymers used are poly[[(2
      methyl-4-methoxyphenyl)imino]-9,9-di-(2'-ethylhexyl)-fluorene-2,7-diyl] (PTAA)
      and poly[2,6-(4,4-bis-(2-ethyhexyl)-4H-cyclopenta [2,1-b;3,4-b']-dithiophene)-alt
      4,7-(2,1,3-benzo thiadiazole)] (PCPDTBT). FTIR in conjunction with
      thermogravimetric analysis data showed that up to 30% of the surfaces for the as
      prepared ZnO nanocrystals and nanorods were occupied by acetate ligands. 1
      Propylamine was found to form covalent coordinate bonds with ZnO and this
      contributes the ability of this co-solvent to promote enhanced ZnO dispersion
      stability. The morphologies of the composites were investigated using optical
      microscopy, AFM and TEM. A strong link was found between colloidal stability of
      the parent ZnO dispersions, extent of nanoparticle aggregation within the
      composites and pK(a) for the conjugate acid of the co-solvent. Electrostatic
      interactions did not control ZnO dispersion stability or composite morphology.
      Extensive nanometer-scale nanoparticle aggregation was evident within the
      composites. This was attributed to incompatibility between the polymer and
      (ligand covered) ZnO nanoparticles. Strategies for reducing uncontrolled
      nanoparticle aggregation are suggested.

PMID- 20138292
TI  - Low-temperature and one-step synthesis of rutile TiO2 aqueous sol by
      heterogeneous nucleation method.
AB  - A phase-pure rutile TiO(2) aqueous sol has been prepared by heterogeneous
      nucleation method with an aqueous peroxotitanate solution as a precursor and
      SnCl(2) as rutile-phase crystalline growth promoter at a temperature as low as
      100  degrees C in one-step process. TEM, XRD and UV-Vis spectra were used to
      characterize the rutile TiO(2) sol. The results reveal that a pure rutile phase
      TiO(2) aqueous sol with average particle sizes of around 20 nm has been
      synthesized, and a transparent film of rutile TiO(2) was also easily prepared by
      dip-coating method. Formation conditions and a possible mechanism of phase
      controlling were investigated. The results show that the presence of the Sn
      content is essential for the formation of a pure rutile TiO(2) phase at low
      temperature, which involves a heterogeneous nucleation mechanism.

PMID- 20138293
TI  - Size controlled synthesis of sub-100 nm monodisperse poly(methylmethacrylate)
      nanoparticles using surfactant-free emulsion polymerization.
AB  - Surfactant-free emulsion polymerization (SFEP) is a well-known technique for the
      production of polymeric nanoparticles that does not require post-synthetic
      cleaning steps. Obtaining hydrophobic particles at sub-100 nm scale, however, is
      quite challenging with this polymerization method. Here, we demonstrate a single
      step synthetic approach that yields poly(methylmethacrylate) (PMMA) nanoparticles
      with controlled sub-100 nm size and relatively high resultant solid content.
      Dynamic light scattering (DLS) was used for the particle characterization.
      Spherical and uniformly sized nanoparticles were confirmed by atomic force
      microscopy (AFM) and scanning electron microscopy (SEM). Acetone was used as a
      cosolvent in order to obtain monodisperse sub-100 nm diameter particles. Stable
      PMMA nanoparticle dispersions were obtained for all formulations where the
      persulfate initiator causes the negative charges on the particle surface. The
      effects of acetone, monomer and initiator concentration were studied to optimize
      average particle hydrodynamic diameter and polydispersity index of the final
      particles. Non-crosslinked monodisperse PMMA nanoparticles (polydispersity index
      less than 0.05) with diameters from 32 nm to 72 nm were synthesized by using this
      method.

PMID- 20138294
TI  - In situ atomic force microscopy of modified dextrin adsorption on hydrophobic and
      hydrophilic layered silicate minerals.
AB  - We have used in situ atomic force microscopy (AFM), captive bubble contact angle
      measurements, and colloid-probe AFM to investigate the adsorption of two modified
      dextrins (a phenyl succinate substituted dextrin, PS Dextrin, and a styrene oxide
      substituted dextrin, SO Dextrin) on the basal plane surfaces of talc and
      clinochlore. The experiments have probed the effect that the polymers have on the
      mineral hydrophobicity and on the expected particle-particle interactions in
      single mineral aggregation. Distinct correlations were seen between the adsorbed
      polymer layer morphology (coverage, thickness) and the ability of the polymers to
      reduce the contact angle of the talc basal plane surfaces (SO Dextrin>PS
      Dextrin). Both polymers were seen to lower the contact angle of clinochlore to an
      apparent limiting value of approximately 25 degrees. The effect of the polymers
      on the forces between hydrophobic surfaces (talc basal plane and a hydrophobised
      titania sphere) and between hydrophilic surfaces (clinochlore cleaved surface and
      a silica sphere) was seen to be a complicated relationship between the adsorbed
      layer morphology and bulk polymer properties, with polymers exhibiting a clear
      tendency to bridge between hydrophobic surfaces. Neither of the dextrins was
      found to encourage attraction between hydrophilic surfaces, in spite of adsorbing
      to a significant extent on the clinochlore cleaved surface.

PMID- 20138295
TI  - Self-similar assemblies of globular whey proteins at the air-water interface:
      effect of the structure.
AB  - We investigated the structure of heat-induced assemblies of whey globular
      proteins using small angle neutron scattering (SANS), static and dynamic light
      scattering (SLS and DLS), and cryogenic transmission electron microscopy (Cryo
      TEM). Whey protein molecules self-assemble in fractal aggregates with a structure
      density depending on the electrostatic interactions. We determined the static and
      dynamic properties of interfacial layer formed by the protein assemblies, upon
      adsorption and spreading at the air-water interface using surface film balance
      and interfacial dilatational rheology. Upon spreading, all whey protein systems
      show a power-law scaling behavior of the surface pressure versus concentration in
      the semi-dilute surface concentration regime, with an exponent ranging from 5.5
      to 9 depending on the electrostatic interactions and the aggregation state. The
      dilatational modulus derived from surface pressure isotherms shows a main peak at
      6-8 mN/m, generally considered to be the onset of a conformational change in the
      monolayer, and a second peak or a shoulder at 15 mN/m. Long-time adsorption
      kinetics give similar results for both the native whey proteins and the
      corresponding self-similar assemblies, with a systematic effect of the ionic
      strength.

PMID- 20138296
TI  - Long-term treatment of cystinosis in children with twice-daily cysteamine.
AB  - OBJECTIVE: Cystinosis causes renal and other organ failure. Treatment with 6
      hourly cysteamine bitartrate (Cystagon, Mylan, Morgantown, West Virginia) reduces
      intracellular cystine and the rate of organ deterioration. A recent study showed
      that an enteric-release cysteamine required less frequent daily dosing. This
      report describes the long-term use of enteric-coated (EC) cysteamine bitartrate
      (Cystagon) in children with cystinosis. STUDY DESIGN: After a pharmacokinetic and
      pharmacodynamic study of EC-cysteamine in children with cystinosis, 5 patients
      remained on twice-daily treatment. White blood cell cystine levels were measured
      12 hours after ingestion every 4 to 8 weeks. These levels were then compared with
      the patient's previous 6-h post-dose levels taken while on regular cysteamine
      bitartrate before entering the study. Blood chemistry was also measured. RESULTS:
      Five children with cystinosis (mean age, 9 years; range, 8 to 17 years) who
      previously took cysteamine bitartrate (mean dose, 47 mg/kg body wt), received EC
      cysteamine for 10 to 27 months (mean dose, 25 mg/kg body wt) and had mean white
      blood cell cystine levels of 0.77 and 0.71 nmol half-cystine/mg protein,
      respectively. During the study period, patients maintained adequate growth and
      there was no significant deterioration in renal or thyroid function. Two children
      were required to restart acid suppression after 6 months on EC-cysteamine
      therapy. CONCLUSIONS: Long-term, twice-daily EC-cysteamine, given at
      approximately 60% of the previous daily dose of cysteamine bitartrate, was
      effective at maintaining white blood cell cystine levels within a satisfactory
      range. There was no significant deterioration in renal or thyroid function.

PMID- 20138297
TI  - Susceptibility-weighted imaging in neurodegeneration in Langerhans cell
      histiocytosis.

PMID- 20138300
TI  - Bacterial enteritis as a risk factor for childhood intussusception: a
      retrospective cohort study.
AB  - OBJECTIVE: To assess the relationship between bacterial enteritis and
      intussusception. STUDY DESIGN: The Patient Administration Systems and
      Biostatistics Activity database from January 2002 to December 2005 was examined
      for clinic visits or hospital admission to a Department of Defense medical
      facility for children age 0-5 years. The study included the International
      Statistical Classification of Diseases and Related Health Problems diagnosis
      related group (DRG) codes for infections with Yersinia enterocolitica,
      Escherichia coli, Shigella species, Salmonella species, and Campylobacter.
      Identified patients were then assessed for the intussusception DRG code for 0-180
      days postinfection. The total number of children enrolled in military treatment
      facilities in the same age group (denominator) was obtained. RESULTS: Bacterial
      enteritis significantly increased the relative risk of intussusception. An
      increased risk was found following infection with Salmonella, E coli, Shigella,
      and Campylobacter. The relative risk for intussusception following any bacterial
      enteritis was 40.6 (95% confidence interval = 28.6-57.5; P < .0001). CONCLUSIONS:
      Bacterial enteritis is a significant risk factor for the subsequent development
      of intussusception in children.

PMID- 20138299
TI  - Two-year neurodevelopmental outcomes of ventilated preterm infants treated with
      inhaled nitric oxide.
AB  - OBJECTIVE: In a randomized multi-center trial, we demonstrated that inhaled
      nitric oxide begun between 7 and 21 days and given for 24 days significantly
      increased survival without bronchopulmonary dysplasia (BPD) in ventilated
      premature infants weighing <1250 g. Because some preventative BPD treatments are
      associated with neurodevelopmental impairment, we designed a follow-up study to
      assess the safety of nitric oxide. STUDY DESIGN: Our hypothesis was that inhaled
      nitric oxide would not increase neurodevelopmental impairment compared with
      placebo. We prospectively evaluated neurodevelopmental and growth outcomes at 24
      months postmenstrual age in 477 of 535 surviving infants (89%) enrolled in the
      trial. RESULTS: In the treated group, 109 of 243 children (45%) had
      neurodevelopmental impairment (moderate or severe cerebral palsy, bilateral
      blindness, bilateral hearing loss, or score <70 on the Bayley Scales II),
      compared with 114 of 234 (49%) in the placebo group (relative risk, 0.92; 95% CI,
      0.75-1.12; P = .39). No differences on any subcomponent of neurodevelopmental
      impairment or growth variables were found between inhaled nitric oxide or
      placebo. CONCLUSIONS: Inhaled nitric oxide improved survival free of BPD, with no
      adverse neurodevelopmental effects at 2 years of age.

PMID- 20138301
TI  - A follow-up study of preterm infants given budesonide using surfactant as a
      vehicle to prevent chronic lung disease in preterm infants.
AB  - OBJECTIVE: Our study of early intratracheal instillation of budesonide using
      surfactant as vehicle showed a significant decrease in death or chronic lung
      disease (CLD) in preterm infants with severe respiratory distress syndrome (RDS).
      We now report the long-term outcome at about 2 to 3 years of age. STUDY DESIGN:
      Of the 75 potential survivors, 67 (90%) were studied (35 budesonide-treated, 32
      control). All infants had birth weight <1500 g and had severe RDS requiring
      intermittent mechanical ventilation shortly after birth. The treated group
      received a mixture of budesonide and surfactant every 8 hours. The control group
      received only surfactant. RESULTS: The physical growth and the neurological
      examinations were comparable between the groups at follow-up. Infants in the
      group treated with budesonide tended to have higher PDI and MDI scores than
      infants in the control group (79 +/- 20 vs 74 +/- 18 and 80 +/- 19 vs 75 +/- 20),
      but these differences were not statistically significant. The incidence of
      neurodevelopmental impairment was 11 (31%) in the treated group and 13 (40%) in
      the control group (P = .367). CONCLUSIONS: Early intratracheal instillation of
      budesonide using surfactant as a vehicle significantly improved pulmonary outcome
      without causing long-term adverse effects.

PMID- 20138302
TI  - Muscular dystrophy revealed by incidentally discovered elevated aminotransferase
      levels.

PMID- 20138303
TI  - Prevalence of congenital heart disease at live birth in Taiwan.
AB  - OBJECTIVES: To investigate the prevalence at live birth of congenital heart
      disease (CHD) in Taiwan. STUDY DESIGN: Patients with CHD born from 2000 to 2006
      were identified from National Health Insurance databases. RESULTS: CHD prevalence
      was 13.08 per 1000 live births: 12.05 (simple, 10.53; severe, 1.51) in male
      infants and 14.21 (simple, 12.90; severe, 1.32) in female infants. Ventricular
      septal defect (VSD; 4.0) was the most common defect, followed by secundum atrial
      septal defect (ASDII; 3.2), patent ductus arteriosus (PDA; 2.0), pulmonary
      stenosis (PS; 1.2), tetralogy of Fallot (TOF; 0.63), coarctation of aorta (CoA;
      0.25), transposition of great arteries (TGA; 0.21), endocardial cushion defect
      (ECD; 0.20), double outlet of right ventricle (DORV; 0.15), total anomalous
      pulmonary venous return (TAPVR; 0.11), aortic stenosis (0.09), hypoplastic left
      heart syndrome (HLHS; 0.062), Ebstein anomaly (0.047), and tricuspid atresia
      (0.046). Female predominance was observed in VSD, ASDII, PDA, and ECD; and male
      predominance was observed in TGA and TOF. Ratios of western prevalence to our
      Asian prevalence were high for HLHS (3.68-4.5), CoA (1.13-1.96), TGA (1.09-1.83),
      and tricuspid atresia (1.09-2.57), but low for PS (0.15-0.99), TOF (0.41-0.92),
      and possibly ASDII. CONCLUSIONS: In this Asian population, the prevalence of CHD
      was at the high end of the reported range, with more PS and TOF, but fewer left
      sided obstructions, TGA, and tricuspid atresia.

PMID- 20138304
TI  - Perspectives and preferences among the general public regarding physician
      selection and board certification.
AB  - OBJECTIVES: To characterize parental attitudes regarding board certification and
      other factors that influence selection of physicians to care for children. STUDY
      DESIGN: A web-based survey administered in 2008 to a random sample of 3621 adults
      >or=18 years of age stratified by parents and non-parents. Proportion of
      respondents who view board certification and other measures of quality as
      important factors in selecting a physician to care for children. RESULTS: Survey
      completion rate was 62%. Almost all (95%) believe it is important or very
      important for doctors who care for children to be assessed on their quality of
      care, receive high ratings from patients (91%), and pass a written test at
      regular intervals (88%). Most reported that recommendations from friends or
      family (84%) and board certification (82%) were important or very important
      factors in choosing a physician for their child. Seventy-seven percent of parents
      stated that they would be likely to change their child's physician if he/she did
      not maintain board certification. CONCLUSION: Parents report a preference for
      board-certified physicians and expect them to participate in Maintenance of
      Certification. Greater understanding of quality measures and the board
      certification process would empower consumers to make more informed decisions in
      selecting a physician for their children.

PMID- 20138305
TI  - Traumatic delivery, diaphragmatic paresis, and "dextrocardia".

PMID- 20138306
TI  - Dietary and physical activity patterns in children with obstructive sleep apnea.
AB  - OBJECTIVE: To assess dietary and physical activity patterns and morning
      circulating blood levels of the orexigenic hormones ghrelin and visfatin in
      children with either obesity, obstructive sleep apnea (OSA), or both conditions.
      STUDY DESIGN: In this cross-sectional design, 5- to 9-year-old participants (n =
      245) from the community were identified. After overnight polysomnography,
      caregivers filled out a food and physical activity questionnaire, and the child
      underwent a fasting blood draw for ghrelin and visfatin plasma levels. RESULTS:
      Compared with control subjects, obese children with OSA ate 2.2-times more fast
      food, ate less healthy food such as fruits and vegetables, and were 4.2-times
      less frequently involved in organized sports. OSA was positively correlated with
      plasma ghrelin levels (R(2), 0.73; P < .0001), but not visfatin levels,
      particularly when obesity was present. CONCLUSION: OSA and obesity in children
      may adversely impact dietary preferences and may be particularly detrimental to
      daily physical activity patterns. Furthermore, increased ghrelin levels support
      the presence of increased appetite and caloric intake in obese patients with OSA,
      which in turn may further promote the severity of the underlying conditions.

PMID- 20138307
TI  - MEALTRAIN: what do inpatient hospitalized children choose to eat?
AB  - Data from the menu ordering system was used to calculate servings/child/day of
      food groups ordered by pediatric inpatients. The children ordered a mean of 5.0
      +/- 0.56 servings of fruits and vegetables/day, which decreased to 3.5 +/- 0.27
      servings when juice was removed. "Foods-to-limit" were ordered 3.8 +/- 0.31
      times/day. Interventions to improve healthier choices are warranted.

PMID- 20138308
TI  - Randomized trial of adenotonsillectomy versus expectant treatment in PFAPA
      (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome:
      is the impasse over?

PMID- 20138309
TI  - Effects of external and internal cues on gait function in Williams syndrome.
AB  - Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, is
      characterized by gait abnormalities that resemble basal ganglia-parkinsonian
      deficits in the internal regulation of stride length. In the current study, we
      explored whether visual or attentional cues would improve gait function in adults
      with WS, when compared to adults with Down syndrome (DS) and neurologically
      normal controls. The spatiotemporal characteristics of gait were measured using
      the GAITRite walkway while participants walked with visual cues set at 20%
      greater than preferred stride length (externally cued), or with an attentional
      strategy of maintaining the stride length without the assistance of visual cues
      (internally cued). Although the WS and DS groups were able to achieve the
      criterion and normalize stride length in both conditions, the WS group
      significantly reduced their gait speed and cadence in the externally cued
      condition when compared to controls. In the internally cued condition, the WS
      group also showed reduced speed and increased intra-individual variability in
      speed and stride time. These findings suggest that the primary deficit is not one
      of difficulty regulating stride length in WS, but rather indicates more
      widespread dysfunction within visuomotor regions.

PMID- 20138310
TI  - [Use of complementary and alternative therapies in a chronic kidney failure
      population in hemodialysis from Saragossa, Spain].

PMID- 20138311
TI  - [C3 spinal cord ependymoma C03].

PMID- 20138312
TI  - [Outcome differences in pediatric patients with type 1 diabetes mellitus
      depending on their HLA-DQ genotypes].
AB  - BACKGROUND AND OBJECTIVE: Our hypothesis is that there is a relationship between
      the short term outcomes of pediatric patients with type I diabetes mellitus and
      their HLA-DQ genotypes. PATIENTS AND METHOD: We performed a descriptive
      epidemiologic study of 129 children and adolescents under 16 years old with type
      1 diabetes mellitus. We studied their HLA DQ genotypes and classified them into
      groups of diabetogenic risk. We studied general clinic and analytic parameters at
      onset of the disease and during a period of 3 years, and the development of
      associated chronic complications. RESULTS: In total, 93.8% of our patients had
      diabetes-risk HLA-DQ genotypes. Onset of the disease occurred earlier in patients
      who belonged to risk group III, and they had less pancreatic reserve. During the
      follow-up period, significant differences in systolic and diastolic blood
      pressure were found in patients in risk group III, and in diastolic blood
      pressure in patients in risk group I. CONCLUSIONS: Patients in risk group III
      have an onset at a lower age and present significant differences in systolic and
      diastolic blood pressure during the follow up period.

PMID- 20138313
TI  - [Utility of enzyme replacement therapy in Fabry disease].
AB  - BACKGROUND AND OBJECTIVE: The lysosomal deposit of sphingolipids secondary to
      alpha-galactosidase-A deficiency causes Fabry disease. The deposit in the
      endothelial cells of the vasa nervorum and the small caliber axons, among other
      structures, results in the characteristic painful neuropathy. It is our objective
      to present the findings of the neuropathy evaluation before and after 18 months
      of agalsidase beta enzyme replacement therapy. MATERIALS AND METHOD: A
      neurological exam, a neurophysiological study measuring sensory and motor
      conduction velocities and amplitudes and a quantitative sensory testing were
      performed on 5 patients with confirmed Fabry disease; quantification on pain
      measurement scales was also done. RESULTS: Prior to treatment, no anomalies were
      found in the conduction velocities or the compound muscular action potential
      amplitudes; the quantitative sensory test was abnormal in all patients. After
      treatment, improvement was seen in the pain scales and the quantitative sensory
      test. CONCLUSIONS: Enzyme replacement therapy with agalsidase beta demonstrated
      subjective and objective benefits related to the painful neuropathy of Fabry
      disease.

PMID- 20138314
TI  - [Internet use by cancer patients and their relatives].

PMID- 20138315
TI  - [The waist to height ratio as an index of cardiovascular risk and diabetes].
AB  - BACKGROUND AND OBJECTIVES: To identify the anthropometric index that best detects
      cardiovascular risk (CVR) and type 2 diabetes (DM2) in the adult Spanish
      population and to determine its cut-off point. SUBJECTS AND METHODS: Cross
      sectional study in the general population (n=6279). Sensitivity and specificity
      were estimated for the anthropometric indexes: abdominal waist, body mass index,
      waist to hip ratio and waist to height ratio (WtHR). The areas of these indexes
      under ROC curve (AUC) were obtained for the following CVR factors: high coronary
      risk computed with Framingham model, Hypertension, Hyperlipemia, DM2, Metabolic
      Syndrome (MS) and Impaired Fasting Glucose (IFG). The odds ratio, with 95%
      confidence interval (CI(95%)), was calculated. RESULTS: WtHR was the index
      showing the highest AUC for DM2 and the remaining CVR factors, varying between
      0.65 (CI(95%)=0.63-0.68) for IFG in men and 0.87 (CI(95%)=0.86-0.89) for MS in
      women. RA/E reached the maximum sensitivity (0.91) and specificity (0.70) in SM
      and its optimal cut-off point was 0.55, which displayed the highest risks amongst
      indexes, varying from 2.30 (1.96-2.70) in IFG to 16'20 (13.68-19.20) in MS.
      CONCLUSIONS: RA/E is the index presenting the best ability to detect DM2 and CVR
      in this population, and it shows the stronger association with them. Its cut-off
      point, 0.55, confirms the convenience of keeping the abdominal waist to less than
      half the height.

PMID- 20138316
TI  - [Platypnea-orthodeoxia syndrome associated with patent foramen ovale].

PMID- 20138317
TI  - [Ultrasound gel: an unusual cause of cold urticaria].

PMID- 20138318
TI  - [Informed consent in clinical trials and pharmacogenetic substudies].

PMID- 20138319
TI  - [Posterior fossa extradural and extracranial hydatid cyst].
AB  - Hydatidosis is an endemic disease in Morocco. Cerebral echinococcosis is a
      relatively rare entity accounting for only 1-2% of all hydatid cysts in humans.
      Extradural hydatid cyst of the posterior fossa is a very uncommon site for the
      disease: only four cases have been reported in the literature. We report the case
      of a 37-year-old admitted for high intracranial pressure. Brain MRI showed an
      extradural and extracranial posterior fossa cyst without enhancement after
      contrast medium injection. Multiple hydatid cysts were removed and the
      histological examination of the tissue sample confirmed the diagnosis. The
      patient was given albendazole postoperatively with good follow-up 6 months later.

PMID- 20138320
TI  - Dual metabolomics: a novel approach to understanding plant-pathogen interactions.
AB  - One of the most well-characterised plant pathogenic interactions involves
      Arabidopsis thaliana and the bacteria Pseudomonas syringae pathovar tomato (Pst).
      The standard Pst inoculation procedure involves infiltration of large populations
      of bacteria into plant leaves which means that metabolite changes cannot be
      readily assigned to the host or pathogen. A plant cell-pathogen co-culture based
      approach has been developed where the plant and pathogen cells are separated
      after 12h of co-culture via differential filtering and centrifugation. Fourier
      transform infrared (FT-IR) spectroscopy was employed to assess the intracellular
      metabolomes (metabolic fingerprints) of both host and pathogen and their extruded
      (extracellular) metabolites (metabolic footprints) under conditions relevant to
      disease and resistance. We propose that this system will enable the metabolomic
      profiling of the separated host and pathogen (i.e. 'dual metabolomics') and will
      facilitate the modelling of reciprocal responses.

PMID- 20138321
TI  - [Neurorehabilitation in parkinsonian syndromes].
AB  - Parkinson's disease is a frequent and major source of motor disability, for which
      physical therapies currently involve less than a third of ambulatory patients and
      are thus underutilized when compared to chemical and surgical treatments.
      However, dopaminergic therapies alone prove unable to prevent worsening of motor
      disability after a number of years. There is rising interest about physical
      neurorehabilitative therapy for Parkinson's disease, for its symptomatic
      therapeutic properties, but also for its potential neuroprotective effects in the
      light of compelling, recent animal literature. The approach to therapy in an
      individual patient may be governed at the most basic level by the disease stage.
      For moderate stages of Parkinson's disease (ambulatory patients who have retained
      a certain degree of physical independence), therapy may focus on the teaching of
      exercises to the patient: strategies established in controlled studies when used
      over few weeks periods include motor strengthening programs in the lower limb,
      high intensity aerobic exercises, attentional strategies using in particular
      verbal instruction sets, sensory cueing, active axial rotation exercises and high
      number repetition of specific tasks. A randomized protocol will soon evaluate the
      concept of asymmetric motor training, combining a strengthening program in
      extensor, abductor, external rotator and supinator muscles and a stretching
      program in their antagonists. For advanced stages (individuals with compromised
      sit-to-stand, ambulation and significant disability), the therapeutic focus may
      shift to the teaching of compensation strategies to the patient and the
      caregiver, both to lessen the effects of motor impairment and to optimize safety.
      A number of these compensatory strategies are reviewed, some being validated in
      controlled protocols. In idiopathic Parkinson's disease, clinicians must continue
      evaluating the symptomatic and perhaps neuroprotective value of physical
      treatment strategies used over the long term. In atypical parkinsonism, physical
      treatments often remain the only realistic methods to improve motor behavior and
      reduce functional deficiencies. The relatively short duration of the effects of
      physical therapies implies that such programs be pursued over long periods of
      time, or repeated frequently, for their benefits to be maintained over time.

PMID- 20138322
TI  - A prospective study of Toxoplasma-positive pregnant women in southern Brazil: a
      health alert.
AB  - We evaluated anti-Toxoplasma gondii IgM-reactive pregnant women seen at a high
      risk pregnancy outpatient clinic. From March 2005 to January 2008 in Parana,
      Brazil, pregnant women seen by the Brazilian Public Health System, in any
      gestational period, who were anti-T. gondii IgM-positive, were followed. Clinical
      symptoms were noted, and tests performed including IgA, IgG avidity,
      ultrasonogram, and amniocentesis (PCR/inoculation in mice). Of 75 patients, 8
      showed low, 3 intermediate and 31 high IgG avidity. Of those who underwent the
      avidity test, 31 (70.5%) were in the second trimester of pregnancy. Thirty-two
      (42.7%) pregnant women received specific treatment. Six received triple
      combination treatment; in three, tachyzoites were isolated, although only one was
      PCR-positive, showing changes in the cerebral sonogram, borderline IgA, and the
      Sabin tetrad. One fetus died, and one non-reactive IgM pregnant woman showed
      ocular recurrence. The municipality of residence, contact with cats during
      adulthood, and ingestion of unpasteurized milk were shown to be important risk
      factors. Congenital toxoplasmosis was observed in a pregnancy referred late for
      treatment. Follow-up of children born to mothers with diagnosed or suspected
      acute toxoplasmosis is crucial in the management of the changes that
      toxoplasmosis may cause.

PMID- 20138323
TI  - Unacceptable attrition among WHO stages 1 and 2 patients in a hospital-based
      setting in rural Malawi: can we retain such patients within the general health
      system?
AB  - A study conducted among HIV-positive adults in WHO clinical stages 1 and 2 was
      followed up at Thyolo District Hospital (rural Malawi) to report on: (1)
      retention and attrition before and while on antiretroviral treatment (ART); and
      (2) the criteria used for initiating ART. Between June 2008 and January 2009,
      1633 adults in WHO stages 1 and 2 were followed up for a total of 282 person
      years. Retention in care at 1, 2, 3 and 6 months for those not on ART (n=1078)
      was 25, 18, 11 and 4% vs. 99, 97, 95 and 90% for patients who started ART (n=555,
      P=0.001). Attrition rates were 31 times higher among patients not started on ART
      compared with those started on ART (adjusted hazard ratio, 31.0, 95% CI 22-44).
      Ninety-two patients in WHO stage 1 or 2 were started on ART without the guidance
      of a CD4 count, and 11 were incorrectly started on ART with CD4 count > or = 250
      cells/mm(3). In a rural district hospital setting in Malawi, attrition of
      individuals in WHO stages 1 and 2 is unacceptably high, and specific operational
      strategies need to be considered to retain such patients in the health system.

PMID- 20138324
TI  - Repair of complex incisional hernias using double prosthetic repair: single
      surgeon experience with 50 cases.
AB  - BACKGROUND: The treatment of complex incisional hernias is still difficult and
      controversial. With technologic developments we can modify and update the
      operative techniques described for treating complex abdominal wall hernias.
      METHODS: This is a prospective study of 50 patients with complex incisional
      hernias undergoing complex abdominal wall herniorrhaphy at a university hospital.
      All patients were evaluated in a multidisciplinary clinic dedicated to abdominal
      wall reconstruction. All patients underwent pre-operative computed tomography.
      Complex incisional hernias were regarded as those with multiple recurrences (>3
      times), a previous mesh complicated by fistula and chronic infection, giant
      diffuse lumbar hernias, an associated parastomal hernia, or hernias developing
      after bariatric surgery. The operative technique was a double reconstruction
      prosthetic mesh. The type of repair as well as clinical, operative, and follow-up
      data were analyzed. RESULTS: Eight patients had considerable loss of tissue, 5
      had trophic skin lesions, and 2 had chronic suppurative infection. The mean size
      of the defects was 18.2 cm. Morbidity included 5 cases of seroma, 2 neuralgias,
      and 2 cutaneous necroses. The mean duration of hospital stay was 5 days (range, 2
      9). Complete follow-up (mean, 48 months; range, 12-108) showed no recurrent
      hernias. CONCLUSION: While awaiting a longer follow-up to confirm the results, we
      conclude that complex incisional hernias can be repaired safely and with a low
      morbidity and recurrence rate by means of a double prosthetic repair technique.

PMID- 20138325
TI  - Fatty pancreas and increased body mass index are risk factors of pancreatic
      fistula after pancreaticoduodenectomy.
AB  - BACKGROUND: Pancreatic fistula (PF) after pancreatoduodenectomy (PD) remains a
      challenging problem. The only commonly accepted risk factor is the soft
      consistency of the pancreatic remnant. METHODS: In all, 100 consecutive patients
      underwent PD. All data, including commonly accepted risk factors for PF and PF
      defined according to the International Study Group of Pancreatic Fistula, were
      collected prospectively. On the pancreatic margin, a score of fibrosis and a
      score of fatty infiltration were assessed by a pathologist blinded to the
      postoperative course. RESULTS: PF occurred in 31% of patients. In univariate
      analysis, male sex, age greater than 58 years, body mass index (BMI) > or =25
      kg/m(2), pre-operative high blood pressure, operation for nonintraductal
      papillary and mucinous neoplasm (IPMN) disease and for ampullary carcinoma,
      operative time, blood loss, soft consistency of the pancreatic remnant, absence
      of pancreatic fibrosis, and presence of fatty infiltration of the pancreas were
      associated with a greater risk of PF. In a multivariate analysis, only BMI > or
      =25 kg/m(2), absence of pancreatic fibrosis, and presence of fatty pancreas were
      significant predictors of PF. A score based on the number of risk factors present
      divided the patient population into 4 subgroups carrying a risk of PF that ranged
      from 7% (no risk factor) to 78% (3 risk factors) and from 0% to 81%, taking into
      account only symptomatic PF (grade B and C). CONCLUSION: The presence of an
      increased BMI, the presence of fatty pancreas, and the absence of pancreatic
      fibrosis as risk factors of PF allows a more precise and objective prediction of
      PF than the consistency of pancreatic remnant alone. A predictive score based on
      these 3 factors could help to tailor preventive measures.

PMID- 20138326
TI  - The polyomavirus BK agnoprotein co-localizes with lipid droplets.
AB  - Agnoprotein encoded by human polyomavirus BK (BKV) is a late cytoplasmic protein
      of 66 amino acids (aa) of unknown function. Immunofluorescence microscopy
      revealed a fine granular and a vesicular distribution in donut-like structures.
      Using BKV(Dunlop)-infected or agnoprotein-transfected cells, we investigated
      agnoprotein co-localization with subcellular structures. We found that
      agnoprotein co-localizes with lipid droplets (LD) in primary human renal tubular
      epithelial cells as well as in other cells supporting BKV replication in vitro
      (UTA, Vero cells). Using agnoprotein-enhanced green fluorescent protein (EGFP)
      fusion constructs, we demonstrate that agnoprotein aa 20-42 are required for
      targeting LD, whereas aa 1-20 or aa 42-66 were not. Agnoprotein aa 22-40 are
      predicted to form an amphipathic helix, and mutations A25D and F39E, disrupting
      its hydrophobic domain, prevented LD targeting. However, changing the
      phosphorylation site serine-11 to alanine or aspartic acid did not alter LD co
      localization. Our findings provide new clues to unravel agnoprotein function.

PMID- 20138327
TI  - Concise synthesis of the pentasaccharide O-antigen corresponding to the Shiga
      toxin producing Escherichia coli O171.
AB  - An expedient total synthesis of a pentasaccharide as its 4-methoxyphenyl
      glycoside corresponding to the Shiga toxin producing Escherichia coli O171 has
      been achieved for the first time in excellent yield. Most of the glycosylation
      steps are highly stereoselective. Stereoselective glycosylation of sialic acid
      derivative was obtained exploiting the nitrile effect of the solvent used.

PMID- 20138328
TI  - The influence of organic ligands on the adsorption of cadmium by suspended matter
      in natural waters studied by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry and electrochemical methods.
AB  - Natural water carrying a great amount of suspended particulate matter (SPM) was
      used as a model system for the study of the competition among organic ligands
      (dietilentetraamine pentaacetic acid, DTPA, nitrilotriacetic acid, NTA, and
      citrate, Cit) and natural complexants (SPM) for cadmium adsorption. Speciation
      diagrams at the pH of the natural sample were obtained by electroanalytical
      techniques, processing the experimental data with the complexation constants and
      the mass balance of the system. Results show that the adsorption equilibrium SPM
      Cd is completely displaced by DTPA but not completely by NTA or Cit. Furthermore,
      larger Cit concentrations increase the amount of adsorbed Cd(II). The increment
      of the complexing capacity may be explained on the basis of SPM-Cit-Cd ternary
      complexes formation. This hypothesis was supported on the results obtained by
      applying for the first time the MALDI-TOF technique in a mixture of SPM, Cd(II),
      organic ligands and their complexes.

PMID- 20138329
TI  - Effect of sampler material on the uptake of PAHs into passive sampling devices.
AB  - Increasing demand for simple and reliable passive samplers for monitoring
      hydrophobic organic contaminants in water has led to increased frequency of use
      of single-phase polymeric sampling devices. In this study, we evaluate the effect
      of sampler material on the passive sampling of polycyclic aromatic hydrocarbons
      (PAHs) in two Norwegian rivers. Low density polyethylene membranes (LDPE),
      silicone strips and semipermeable membrane devices (SPMDs) with the exact same
      surface area and conformation were exposed in the Drammen River for overlapping
      exposures of 24 and 51 d, under identical hydrodynamic conditions. Dissipation
      rates of performance reference compounds (PRCs) spiked in all samplers were
      consistent and demonstrated no significant differences in sampler-water analyte
      exchange kinetics between the two exposures. The transition to fully boundary
      layer-controlled uptake shown by PRC dissipation rates was confirmed by
      investigating PAH masses absorbed by the samplers. Masses of analytes with log
      K(ow)>4.5 absorbed into the samplers were similar and independent of the sampler
      material used, generally indicating for these compounds that the boundary layer
      dominated the resistance to mass transfer. The very low variability in analyte
      masses absorbed across sampler types observed here indicates that much of the
      overall variability in dissolved contaminant concentrations seen in passive
      sampler intercomparison studies is likely the result of the uncertainty
      associated with sampler-water partition coefficients and PRC dissipation rates.
      PRC dissipation rates and ratios of masses absorbed over 51 and 24 d for these
      compounds demonstrated integrative sampling over 51 d and no major effects of
      biofouling on sampling. The equivalence of data obtained using silicone strips
      and SPMDs supports the use of single-phase polymeric passive sampling devices.

PMID- 20138330
TI  - Reappraisal of mesenchymal chondrosarcoma: novel morphologic observations of the
      hyaline cartilage and endochondral ossification and beta-catenin, Sox9, and
      osteocalcin immunostaining of 22 cases.
AB  - Mesenchymal chondrosarcoma, a rare malignant round cell and hyaline cartilage
      tumor, is most commonly intraosseous but can occur in extraskeletal sites. We
      intensively observed the morphology and applied Sox9 (master regulator of
      chondrogenesis), beta-catenin (involved in bone formation, thought to inhibit
      chondrogenesis in a Sox9-dependent manner), and osteocalcin (a marker for
      osteoblastic phenotype) to 22 central nervous system and musculoskeletal
      mesenchymal chondrosarcoma. Cases of mesenchymal chondrosarcoma were retrieved
      and reviewed from our files. Immunohistochemistry and follow-up were obtained on
      mesenchymal chondrosarcoma and tumor controls. Twenty-two mesenchymal
      chondrosarcomas included 5 central nervous system (all female; mean age, 30.2;
      mean size, 7.8 cm; in frontal lobe [n = 4] and spinal cord [n = 1]) and 17
      musculoskeletal (female-male ratio, 11:6; mean age, 31.1; mean size, 6.2 cm; 3
      each of humerus and vertebrae; 2 each of pelvis, rib, tibia, neck soft tissue;
      one each of femur, unspecified bone, and elbow soft tissue). The hyaline
      cartilage in most tumors revealed a consistent linear progression of chondrocyte
      morphology, from resting to proliferating to hypertrophic chondrocytes. Sixty
      seven percent of cases demonstrated cell death and acquired osteoblastic
      phenotype, cells positive for osteocalcin at the site of endochondral
      ossification. Small round cells of mesenchymal chondrosarcoma were negative for
      osteocalcin. SOX9 was positive in both components of 21 of 22 cases of
      mesenchymal chondrosarcoma. beta-Catenin highlighted rare nuclei at the interface
      between round cells and hyaline cartilage in 35% cases. Control skull and central
      nervous system cases were compared, including chondrosarcomas and small cell
      osteosarcoma, the latter positive for osteocalcin in small cells. Mesenchymal
      chondrosarcoma demonstrates centrally located hyaline cartilage with a linear
      progression of chondrocytes from resting to proliferative to hypertrophic, which
      undergoes endochondral ossification, recapitulating growth plate cartilage and
      suggesting that this component of mesenchymal chondrosarcoma may be a
      differentiated (benign or metaplastic) component of a malignant metastasizing
      tumor. This hyaline cartilage component is morphologically different from
      cartilage of control chondrosarcoma. Mesenchymal chondrosarcoma can be separated
      from small cell osteosarcoma, using Sox 9 for cartilage and osteocalcin for
      osteoblastic phenotype. Rare nuclear beta-catenin expression at the interface
      between hyaline cartilage and small round cells potentially implicates the
      APC/Wnt pathway during endochondral ossification in morphologically benign
      hyaline cartilage component of mesenchymal chondrosarcoma.

PMID- 20138331
TI  - A new reconstruction of Sts 14 pelvis (Australopithecus africanus) from computed
      tomography and three-dimensional modeling techniques.
AB  - The purpose of this study is to propose a new reconstruction of the
      australopithecine Sts 14 pelvis from original fossils. Digital models created
      from CT images allow us to perform mirroring operations, select valid regions
      after digital interposition, and reassemble parts. The key-element of the
      reconstruction is the sacroiliac joint, restored from right and left articular
      surfaces, which places of the pubic symphysis close to the sagittal plane. The
      complete pelvis is obtained by 3D model mirroring of hip-bone and sacrum. The
      present reconstruction of the Sts 14 pelvis is consistent with Schmid's (1983)
      [Folia Primatol. 40, 283-306, 1983] and Hausler and Schmid's A.L. 288-1 [J. Hum.
      Evol. 29, 363-383, 1995] pelvic reconstructions by illustrating a relatively
      platypelloid shape of the pelvic cavity and laterally inclined iliac blades. The
      pelvic morphology suggests that australopithecines had a less posteriorly tilted
      sacrum in erect posture than modern humans. As compared with Lovejoy's [Am. J.
      Phys. Anthropol. Suppl. 50, 460, 1979] A.L. 288-1 pelvic reconstruction, the less
      transversely flattened shape of the Sts 14 pelvic cavity led to obstetrical
      mechanics characterized as in humans by ante-ischiatic birth and a curved
      trajectory. We deduce a human-like movement of rotation and flexion of the fetal
      skull in the Sts 14 pelvic cavity.

PMID- 20138332
TI  - Integrated risk assessment and risk governance as socio-political phenomena: a
      synthetic view of the challenges.
AB  - To call for integration in risk assessment and governance as a self-evident goal
      is deceptively easy. For more insight, we ask: what level and kind of integration
      and for what purposes is needed and sufficient? What opportunities and obstacles
      can be identified for integrative treatment of risks? What causes and impacts are
      there of developments in risk integration? To answer these questions we
      investigate the socio-political processes and factors surrounding integrated risk
      assessment and risk governance through a combination of literature reviews and
      original research. We emphasize regulatory assessment and governance of risks
      associated with chemicals in the EU, but we link them with other areas to better
      grasp options and problems in integration. We relate the problems to political
      factors and barriers in sector and vertical integration, including deviating
      interests, and further to conflicting information, concepts and mindsets. Risk
      assessment and risk governance involve varying notions of risks and knowledge,
      with tensions between stressor- or impact-oriented, exclusive or inclusive,
      positivist or relativist, and fixed or reflexive notions and approaches. These
      tensions influence the trajectories of integration between sectors, actors and
      regions, constraining the fulfillment of ideals of integrated governance. We
      conclude that risk assessment and governance can be integrated, harmonized and
      innovated to a limit only, but this limit is variable and flexible, and provides
      opportunities especially if attention is paid to the socio-political contexts,
      value choices and decision structures in each case. Generally, the results
      underline a reflexive approach whereby the meanings, framings and implications of
      risk integration are probed in open processes of deliberation and negotiation, as
      a learning process to transcend the formal and prescriptive modes of regulation
      and knowledge generation.

PMID- 20138333
TI  - Mice with deleted multimerin 1 and alpha-synuclein genes have impaired platelet
      adhesion and impaired thrombus formation that is corrected by multimerin 1.
AB  - BACKGROUND: Multimerin 1 is a stored platelet and endothelial cell adhesive
      protein that shows significant conservation. In vitro, multimerin 1 supports
      platelet adhesion and it also binds to collagen and enhances von Willebrand
      factor-dependent platelet adhesion to collagen. As selective, multimerin 1
      deficient mice have not been generated, we investigated multimerin 1 effects on
      platelet adhesion using a subpopulation of C57BL/6J mice with tandem deletion of
      the genes for multimerin 1 and alpha-synuclein, a protein that inhibits alpha
      granule release in vitro. We postulated that multimerin 1/alpha-synuclein
      deficient mice might show impaired platelet adhesive function from multimerin 1
      deficiency and increased alpha-granule release from alpha-synuclein deficiency.
      METHODS: Platelet function was assessed by intravital microscopy, after ferric
      chloride injury, using untreated and human multimerin 1-transfused multimerin
      1/alpha-synuclein deficient mice, and by in vitro assays of adhesion, aggregation
      and thrombin-induced P-selectin release. RESULTS: Multimerin 1/alpha-synuclein
      deficient mice showed impaired platelet adhesion and their defective thrombus
      formation at sites of vessel injury improved with multimerin 1 transfusion.
      Although multimerin 1/alpha-synuclein deficient platelets showed increased P
      selectin release at low thrombin concentrations, they also showed impaired
      adhesion to collagen, and attenuated aggregation with thrombin, that improved
      with added multimerin 1. CONCLUSIONS: Our data suggest that multimerin 1 supports
      platelet adhesive functions and thrombus formation, which will be important to
      verify by generating and testing selective multimerin 1 deficient mice.

PMID- 20138334
TI  - The GPIIIa PlA polymorphism and the platelet hyperactivity in Tunisian patients
      with stable coronary artery disease treated with aspirin.
AB  - BACKGROUND: Various genetic polymorphisms have been proposed to explain the
      persistent platelet hyperactivity (HPR) under aspirin treatment. PlA polymorphism
      of platelet GPIIIa receptor has been largely studied. However, its influence on
      platelet sensitivity to aspirin remains controversial. OBJECTIVES: The aim of
      this prospective study is to investigate whether this PlA polymorphism is
      associated with a greater prevalence of HPR in stable coronary artery disease
      patients Material and Methods: 188 stable coronary artery disease patients were
      included. Platelet aspirin inhibitory effect was determined with PFA-100 using
      Collagen/Epinephrine closure time (CEPI-CT). A CEPI-CT<160sec was defining the
      HPR status. GPIIIa PlA polymorphism was established using polymerase chain
      reaction and classical restriction fragments length polymorphism. RESULTS: The
      observed frequencies of different genotypes were not different from those
      predicted by the Hardy-Weinberg equilibrium: PlA1/lA1 (55.3%), PlA1/PlA2 (39.4%)
      and PlA2/PlA2 (5.3%). HPR patients with inadequate aspirin inhibition were
      significantly more often homozygous PlA1/A1 (65.4% vs. 47.7%, p=0.015). After
      multivariate analysis, PlA1/A1 genotype was the only independent risk factor for
      persistent HPR (OR: 2.07; 95% CI [1.14 to 3.76; p=0.016). CONCLUSION: In CAD
      patients receiving daily low dose of aspirin, there is a significant and
      independent association between the expression of GPIIIa PlA1 allele and the
      occurrence of persistent HPR detected with PFA-100.

PMID- 20138335
TI  - Posttranslational modifications and activity of natural and recombinant tissue
      factor.
AB  - Tissue factor is a membrane protein, which in a complex with factor VIIa
      initiates in vivo blood coagulation. Due to the scarcity of natural tissue factor
      protein, most studies have relied upon recombinant tissue factor forms. However,
      there have been only cursory experimental comparisons of natural and recombinant
      tissue factor proteins. Our preliminary data suggested that placental tissue
      factor in a complex with factor VIIa was more efficient activator of factor X
      than the recombinant protein. After deglycosylation, both forms of tissue factor
      showed almost an identical activity in the extrinsic factor Xase. Analyses using
      tryptic digestion and mass-spectrometry revealed that the levels of glycosylation
      and the composition of carbohydrates present in natural placental tissue factor
      were different than those in its recombinant counterpart. These data indicate
      that natural and recombinant tissue factor proteins differ in their
      posttranslational modifications and that these differences translate into
      different cofactor activity. Thus the use of recombinant tissue factor proteins
      for the quantitation of natural tissue factor is misleading.

PMID- 20138336
TI  - Cell death causes relocalization of photosensitizing fluorescent probes.
AB  - When cultured cells are treated with fluorescent organelle probes or
      photosensitizer agents, a characteristic redistribution of fluorescence in cell
      structures occurs frequently after light irradiation. It is currently assumed
      that such changes, referred to as relocalizations of the fluorescent compounds,
      represent an important aspect of the photodynamic process, which is based on the
      excitation of photosensitizers by light in the presence of oxygen. As cell damage
      and death result from the oxidative stress induced by photodynamic treatments, we
      have studied here the redistribution of acridine orange (AO) and 3,3'-dimethyl
      oxacarbocyanine (DiOC(1)(3)) fluorescence after incubation of HeLa cell cultures
      with these compounds followed by blue light irradiation to achieve lethal
      effects. The relocalization of dyes from their original labeling sites (AO:
      lysosomes, DiOC(1)(3): mitochondria) to nucleic acid-containing structures
      (cytoplasm, nuclei and nucleoli) appeared clearly associated with cell death.
      Therefore, the relocalization phenomenon simply reflects fluorescence changes due
      to the different affinity of these dyes for living and damaged or dead cells. As
      fluorescent probes are often photosensitizers, prolonged light exposures using
      fluorescence microscopy will produce lethal photodynamic effects with
      relocalization of the fluorescent signal and changes in the cell morphology.

PMID- 20138337
TI  - Hand metastasis from renal carcinoma.
AB  - Renal carcinoma may develop metachronous distant metastases without evidence of
      regional or local disease recurrence. These lesions may be misdiagnosed because
      of its benign-like appearance and lack of evidence of other disease spread.

PMID- 20138338
TI  - The impact of income and education on dietary habits in stone formers.
AB  - PURPOSE: To evaluate the impact of socioeconomic status (SES) on dietary habits
      in stones formers (SF) as there is an obvious association between dietary habits
      and risks of urolithiasis. METHODS: SF were selected to complete the Diet History
      Questionnaire (DHQ) and an SES questionnaire. Meaningful dietary constituents
      were generated from DHQ raw data. SF were considered of lower SES if they had
      less than 12 years of education and lived below the poverty level. RESULTS:
      Ninety-nine SF completed the DHQ and SES questionnaires. Thirty-seven SF had low
      education, whereas 62 high education levels. Significant mean dietary
      constituents by education level (lower vs higher) were calcium (1058.4 vs 705.0
      mg/d), carbohydrate (394.9 vs 253.4 g/d), cholesterol (398.7 vs 253.4 mg/d),
      dietary fiber (24.6 vs 17.9 g/d), food energy (3307.9 vs 2051.5 kcal/d),
      phosphorus (1903.9 vs 1220.1 mg/d), potassium (4195.6 vs 2861.5 mg/d), and sodium
      (5136.8 vs 3050.5 mg/d) (P <.05). Thirty-four SF were below the poverty level and
      60 above it. Significant mean dietary constituents by annual income (below vs
      above poverty level) were carbohydrate (397.6 vs 259.3 g/d), dietary fiber (26.1
      vs 17.8 g/d), magnesium (481.8 vs 316.7 mg/d), and potassium (4141.9 vs 3031.6
      mg/d), (P <.05). CONCLUSIONS: SES impacts dietary habits and this may strongly
      influence stone formation and recurrence. Therefore, dietary counseling and
      modification as prevention for further stone formation should be more emphasized
      in SF of lower SES.

PMID- 20138339
TI  - Gender and renal cancer: do variations in clinical presentation and imaging
      patterns explain observed differences between males and females?
AB  - OBJECTIVES: To determine whether gender variations in imaging and healthcare
      access are contributing to observed differences in renal cancer, we examine the
      initial events in the diagnosis of renal masses in a cohort of patients and
      correlate it with detailed data on imaging patterns over the same period.
      METHODS: A total of 308 patients diagnosed with a renal mass over 11 years were
      reviewed. Information on symptoms, imaging, diagnosing physician, demographics,
      and pathology was gathered. Data on imaging for 1 862 485 patients at our
      institution over the same period were also collected. The data were analyzed for
      temporal trends, gender variations, and differences between incidental and
      nonincidental masses. RESULTS: Females presented with smaller masses (4.8 vs 6.0
      cm, P = .0064), and were less likely to have clear cell tumors (58.7% vs 63.4%, P
      = .049). A total of 66.9% of female and 61.1% of male cases were incidental (not
      significant). In both males and females, primary care physicians were the most
      common diagnosing physicians (47.4% and 49.6%, respectively). Gynecologic
      complaints were an uncommon cause of diagnosis for women (5.3%). Computerized
      tomography was the most common diagnosing modality for both males and females
      (69.1% and 63.2%, respectively). Ultrasound as the diagnosing modality did not
      reach statistical significance between males and females (23.4% and 28.6%,
      respectively). During the 11- year period, women underwent more imaging studies
      overall than men (19.7% difference), but the difference was lower when only
      considering studies that can diagnose renal masses (6.4% difference).
      CONCLUSIONS: Gender variations in imaging rates and presentation for
      obstetrics/gynecology concerns by females did not lead to a significant
      difference in incidental diagnosis and do not appear adequate to explain gender
      differences in renal cancer presentation.

PMID- 20138340
TI  - A novel 5-part Percutaneous Access Needle with Glidewire technique (5-PANG) for
      percutaneous nephrolithotomy: our initial experience.
AB  - OBJECTIVES: To describe the use of an innovative 5-part Percutaneous Access
      Needle with Glidewire (5-PANG), a novel technique in an attempt to make
      percutaneous nephrolithotomy (PCNL-a routinely performed procedure) tract
      establishment a fast, safe, and less cumbersome procedure. METHODS: An access
      needle (5-PANG needle) was designed and fabricated at the Institute of Urology,
      Dhule, and used for percutaneous renal access during PCNL. RESULTS: The 5-PANG
      technique was used in 55 cases (57 renal units). It was used for all calyceal
      punctures, all types of stones, renal anatomies, and for second-time surgeries (8
      cases). The mean time required (from the stage of the successful puncture using
      the first 3 parts of the needle till the placement of Alken's rod) was 44.54
      seconds. The radiation time was a mean of 3.34 seconds. Punctured calyx and tract
      size did not affect the results. Visual clarity was good in 85.9% cases. No case
      had to be converted to conventional method or abandoned. There were no intra- or
      postoperative complications related to the 5-PANG. CONCLUSIONS: We find the 5
      PANG technique safe, fast, effective, and inexpensive. It is easy to learn and
      master. We recommend this technique over the standard initial tract dilatation
      techniques.

PMID- 20138341
TI  - The effect of epigenetic therapy on congenital neurogenic bladders--a pilot
      study.
AB  - OBJECTIVES: To demonstrate that human smooth muscle cells derived from neurogenic
      bladders produce more collagen in vitro than smooth muscle cells derived from
      normal bladders, and that epigenetic therapy may normalize this increased
      collagen production. METHODS: Human smooth muscle cells from normal (n = 3) and
      neurogenic bladders (n = 3) were cultured in normal culture media and at
      different concentrations of the histone deacetylase inhibitors trichostatin A,
      valproic acid, and the DNA methylation inhibitor 5-azacytidine (5-aza). Collagen
      type I and III gene expression was measured using real-time quantitative reverse
      transcription-polymerase chain reaction after varying doses of drug exposure.
      Cell viability was measured using trypan blue. RESULTS: The smooth muscle cells
      from neurogenic bladders released significantly more collagen than the normal
      bladder cells (mean 4.1 vs 1.8 microg/mL in control media) when grown in normal
      conditions. Treatment with trichostatin A at 50 ng/mL decreased the collagen
      level in cells from neurogenic bladders to almost normal levels (2.1 microg/mL).
      In addition, valproic acid treatment decreased collagen types I and III gene
      expression relative to controls, with maximal effect at 300 mg/mL. These
      treatments had little effect on cell viability. CONCLUSIONS: Histone deacetylase
      inhibitors decreased collagen production of smooth muscle cells from neurogenic
      bladders in vitro. These agents may be a means of effectively preventing bladder
      fibrosis in patients with this condition.

PMID- 20138342
TI  - Ketorolac is underutilized after ureteral reimplantation despite reduced hospital
      cost and reduced length of stay.
AB  - OBJECTIVES: To examine patterns of ketorolac use and its association with
      hospital outcomes. Although ureteral reimplantation (UR) reliably corrects
      vesicoureteral reflux, postoperative pain and bladder spasm often occur. Multiple
      studies show that ketorolac markedly reduces postoperative pain after UR, but
      there is no information on whether ketorolac is routinely used. METHODS: The
      Pediatric Health Information System is a national database collected by over 40
      US children's hospitals. We identified children with primary vesicoureteral
      reflux who underwent UR between 2003 and 2008. Billing data were reviewed to
      identify patients who received ketorolac during hospitalization. Multivariate
      models were used to examine ketorolac use and postoperative outcomes including
      complication rates, length of stay, and hospital costs. RESULTS: We identified
      12,239 children undergoing UR, 6362 (52%) of whom received ketorolac
      postoperatively. Factors associated with ketorolac use include older age, female
      gender, and decreased disease severity (all P <.0001). Ketorolac use was
      associated with reduced length of stay (2 vs 3 days, P <.0001) and decreased
      hospital costs ($14,223 vs $16,382, P <.0001). Complication rates were slightly
      higher in patients not receiving ketorolac (4% vs 3%). After adjusting for
      confounding factors, ketorolac use remained highly associated with decreased
      length of stay (P = .01) and decreased costs (P = .002), with no significant
      differences in complication rates (P = .4). CONCLUSIONS: In a contemporary
      nationwide sample, only half of children undergoing UR received ketorolac.
      Ketorolac use is independently associated with reduced procedure costs and
      reduced length of stay after UR, without increased complications. This suggests
      underutilization of ketorolac after UR.

PMID- 20138343
TI  - An unusual complication during inflatable penile prosthesis implantation.
AB  - Bladder injury during inflatable penile prosthesis implantation is a rare
      complication. Previous pelvic surgery or radiation can predispose to this unusual
      complication. We describe a case where the inflatable penile prosthesis reservoir
      was implanted into the urinary bladder.

PMID- 20138344
TI  - Subcutaneous cod liver oil injection for penile augmentation: review of
      literature and report of eight cases.
AB  - OBJECTIVES: To study the presentations and treatment outcome of 8 consecutive
      patients for whom cod liver oil was injected in the subcutaneous area of their
      penises by a lay person for purpose of augmentation. METHODS: Various amounts of
      cod liver oil were injected in the subcutaneous area of the penis of 8 low
      socioeconomic class patients by a nonmedical person. They presented by various
      complications ranging from paraphimosis up to abscess formation and necrosis of
      penile skin. All the patients underwent emergency initial surgical intervention
      ranging from dorsal preputial slit to skin debridement. Definitive surgical
      treatment was carried out using local penile flap and V-Y plasty. RESULTS: The
      severity of complications was correlated to the amount of oil injected and the
      time interval between injections and presentation. All the 8 patients were cured
      after different staged surgical procedures. The postoperative course was
      uneventful in 6 patients, and 2 patients suffered from wound infection after the
      secondary treatment. All patients had acceptable cosmetic and functional outcome,
      and were satisfied regarding the length of the penis. None reported erectile
      dysfunction. CONCLUSIONS: Increased public awareness is indicated to avoid this
      problem. Early detection and prompt treatment give acceptable anatomic and
      functional results.

PMID- 20138345
TI  - Epidemiology and pathology of HPV disease in males.
AB  - It is currently recognized that besides the significant impact of human
      papillomavirus (HPV) infection in females, HPV causes substantial disease in men
      as well. Genital warts are a common manifestation of male infection with HPV.
      Genital warts are highly infectious and approximately 65% of people who have sex
      with an infected partner will develop warts themselves. More than 90% of genital
      warts are caused by non-oncogenic HPV types 6 and 11. In addition, recurrent
      respiratory papillomatosis is a rare disease most often associated with HPV types
      6 and 11. Several cancers of the anogenital tract and upper aero-digestive tract,
      and their precursor lesions in men are now understood to be caused by infection
      with sexually transmitted HPV. For example, there is increasing incidence of anal
      cancer in western countries; however, there are limited data on its primary
      cause, anal canal HPV infection. Genital HPV infection is very common in men with
      an ongoing international study estimating a prevalence of 65.2% in asymptomatic
      males aged 18-70 years. Lifetime number of sexual partners was the most
      significant risk factor for the acquisition of HPV infection (P<0.05), and
      circumcision has been associated with reduced detection of HPV infection in men.
      HPV infections may be less likely to persist in men than in women. In men, the
      median time to clearance of any HPV infection was 5.9 months, with 75% of
      infections clearing within 12 months. More data are needed to better understand
      the natural history of HPV infection. Although the quadrivalent HPV vaccine has
      been shown to be effective and safe in men, low awareness of HPV in males may be
      a barrier to its use for the prevention of HPV infection.

PMID- 20138346
TI  - Total laparoscopic hysterectomy with pelvic/aortic lymph node dissection for
      endometrial cancer--a consecutive series without case selection and comparison to
      laparotomy.
AB  - OBJECTIVE: To determine feasibility of duplicating operative time and nodal yield
      of "open" procedures by using laparoscopy for clinically localized endometrial
      cancer without case selection and eliminating influence of BMI on conversion.
      METHODS: In this retrospective study 210 consecutive patients were laparoscoped
      between July, 2006 and November, 2009 to perform total laparoscopic hysterectomy
      with bilateral salpingoophorectomy and pelvic/aortic lymph node dissection
      (TLH/BSO/LND) using pulsed bipolar cautery to complete all phases of the
      procedure. Outcomes ("Scope" group) are compared to historic consecutive
      TAH/BSO/LND controls ("Open" group) operated on 2004-2009 and "open" series in
      the literature. RESULTS: Two hundred (95.2%) procedures were completed
      laparoscopically, 3 (1.4%) required a minilaparotomy to remove the uterus, and 7
      (3.3%) were converted to complete the hysterectomy with some portion of LND.
      There was no influence of BMI (P=0.688), age (P=0.748) or the number of prior
      abdominal operations (P=0.875) on probability of conversion (Logistic
      regression). The mean age, BMI, number of prior abdominal procedures, and GOG
      performance status were equivalent in both study groups. The mean operative time
      was 139.5 min (IQR 125-152) for the "Scope" group and 128.4 min (IQR 105-124) for
      the "Open" group (P=0.008). The mean nodal yield was 34.7 (IQR 24-40) for the
      "Scope" group and 25.7 (IQR 18-30) for the "Open" group (P<0.001). The mean
      hospital stay was 3.2 days (IQR 2-4) for the "Scope" group and 7.9 days (IQR 5-9)
      for the "Open" group (P<0.001). CONCLUSIONS: For clinically localized endometrial
      cancer, TLH/BSO/LND can functionally duplicate operative time equivalent to
      "open" procedures, while improving nodal yield, and minimizing influence of BMI
      on conversion to laparotomy and case selection.

PMID- 20138347
TI  - Prevention strategies against human papillomavirus in males.
AB  - Sexually transmitted human papillomavirus (HPV) infection is very common in men
      and women. Oncogenic HPV is strongly associated with cancers and high-grade
      dysplasias of the anogenital tract, including the anus, penis, and also a
      proportion of oropharyngeal cancers. In reducing male disease burden, some
      consider screening and treatment for high-grade anal dysplasia (AIN) to prevent
      anal cancer in high-risk populations. Such strategies have wide implications for
      the workforce, and require more evidence for the optimal management of AIN. Male
      sexual behavior, with consequent HPV infection and disease contribute to
      considerable disease burden in females. Hence, inclusion of males in prophylactic
      HPV vaccination programs should prevent HPV-related disease in males as well as
      substantially reducing disease burden in females. Clinical trial data in males 16
      26 years for the quadrivalent vaccine show it is well tolerated, induces a strong
      type-specific immunological response comparable to that of females, and reduced
      vaccine HPV-type-related genital infection, as well as disease. Cost-benefit
      analyses and mathematical modeling show that the most cost-effective strategy
      involves routine administration of this vaccine to 12-year-old females, with
      catch-up vaccination of 12- to 24-year-olds, with the most effective strategy in
      disease reduction including men and/or boys in the program. Such a vaccination
      strategy including 12-year-old boys is projected by 2050 to reduce HPV 16
      infection by 88-94% in females and 68-82% in males, plus the aforementioned male
      HPV- related cancers by 22-27%. Therefore, inclusion of males in an HPV
      vaccination program is likely to have significant health and economic benefits
      over and above those observed from current female-only programs. However,
      comprehensive cost-benefit analyses are needed to determine the efficacy of these
      programs in the overall population. Such analyses will be crucial for the design,
      acceptance, and implementation of these vaccination programs into clinical
      practice globally.

PMID- 20138349
TI  - Cats and dogs: an attractive remedy versus atopy?

PMID- 20138350
TI  - Advances in environmental and occupational respiratory diseases in 2009.
AB  - The year 2009 led to a number of significant advances in environmental and
      occupational allergic diseases. The role of exposure to environmental pollutants,
      respiratory viruses, and allergen exposure showed significant advances. New
      allergens were identified. Occupational asthma and the relationship of
      complementary and alternative medicine to allergic diseases were extensively
      reviewed. New approaches to immunotherapy, novel vaccine techniques, and methods
      to reduce risks for severe allergic disease were addressed.

PMID- 20138351
TI  - Cats and dogs: an attractive remedy versus atopy?

PMID- 20138352
TI  - Adolescents with asthma or atopic eczema have more febrile days in early
      childhood: a possible explanation for the connection between paracetamol and
      asthma?

PMID- 20138353
TI  - Method agreement analysis: a review of correct methodology.
AB  - The correct approach to analyzing method agreement is discussed. Whether we are
      considering agreement between two measurements on the same samples
      (repeatability) or two individuals using identical methodology on identical
      samples (reproducibility) or comparing two methods, appropriate procedures are
      described, and worked examples are shown. The correct approaches for both
      categorical and numerical variables are explained. More complex analyses
      involving a comparison of more than two pairs of data are mentioned and guidance
      for these analyses given. Simple formulae for calculating the approximate sample
      size needed for agreement analysis are also given. Examples of good practice from
      the reproduction literature are cited, and common errors of methodology are
      indicated.

PMID- 20138354
TI  - Developmental competence and mRNA expression of preimplantation in vitro-produced
      embryos from prepubertal and postpubertal cattle and their relationship with
      apoptosis after intraovarian administration of IGF-1.
AB  - Recombinant human Insulin-like growth factor-I (hIGF-1) was administered to one
      ovary of prepubertal and postpubertal cattle to determine its effects on (1)
      oocyte developmental competence, (2) the expression pattern of six
      developmentally important genes (GLUT3, GLUT8, AKT1, BCL-XL, BAD, and BAX), and
      (3) its relationship with apoptosis (female Holstein-Friesian). Oocytes were
      retrieved from 7- to 10-mo-old prepubertal dairy calves (preP), 11- to 18-mo-old
      postpubertal heifers (postP), and cows via ultrasound-guided follicular
      aspiration. Immature oocytes were matured in vitro then fertilized and cultured
      up to the blastocyst stage. Apoptosis was determined by terminal deoxynucleotidyl
      transferase nick-end labeling (TUNEL) in 8-d blastocysts. Similar low blastocyst
      yields were observed in the IGF-1-treated preP group (11.2+/-2.4%), the control
      preP group (10.4+/-3.0%), and in the IGF-1 postP group (10.9+/-2.3%). These were
      lower (P<or=0.01) compared with the control postP group (21.2+/-3.8%) and with
      cows (23+/-3.7%). The expression profile of the six genes was partly affected by
      age and IGF-1 treatment. Apoptosis was correlated with the age of the oocyte
      donors and was increased in blastocysts derived from prepubertal heifers. Results
      show that apoptosis is a critical feature of the acquisition of developmental
      competence of oocytes from prepubertal cattle and that IGF-1 did not beneficially
      affect oocyte developmental competence.

PMID- 20138356
TI  - Closed-loop insulin delivery: is the Holy Grail near?

PMID- 20138357
TI  - Manual closed-loop insulin delivery in children and adolescents with type 1
      diabetes: a phase 2 randomised crossover trial.
AB  - BACKGROUND: Closed-loop systems link continuous glucose measurements to insulin
      delivery. We aimed to establish whether closed-loop insulin delivery could
      control overnight blood glucose in young people. METHODS: We undertook three
      randomised crossover studies in 19 patients aged 5-18 years with type 1 diabetes
      of duration 6.4 years (SD 4.0). We compared standard continuous subcutaneous
      insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery
      after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery
      and standard treatment after exercise (n=10; APCam03). Allocation was by computer
      generated random code. Participants were masked to plasma and sensor glucose. In
      APCam01, investigators were masked to plasma glucose. During closed-loop nights,
      glucose measurements were fed every 15 min into a control algorithm calculating
      rate of insulin infusion, and a nurse adjusted the insulin pump. During control
      nights, patients' standard pump settings were applied. Primary outcomes were time
      for which plasma glucose concentration was 3.91-8.00 mmol/L or 3.90 mmol/L or
      lower. Analysis was per protocol. This trial is registered, number
      ISRCTN18155883. FINDINGS: 17 patients were studied for 33 closed-loop and 21
      continuous infusion nights. Primary outcomes did not differ significantly between
      treatment groups in APCam01 (12 analysed; target range, median 52% [IQR 43-83]
      closed loop vs 39% [15-51] standard treatment, p=0.06; <or=3.90 mmol/L, 1% [0-7]
      vs 2% [0-41], p=0.13), APCam02 (six analysed; target range, rapidly 53% [48-57]
      vs slowly absorbed meal 55% [37-64], p=0.97; <or=3.90 mmol/L, 0% [0-4] vs 0% [0
      0], p=0.16]), and APCam03 (nine analysed; target range 78% [60-92] closed loop vs
      43% [25-65] control, p=0.0245, not significant at corrected level; <or=3.90
      mmol/L, 10% [2-15] vs 6% [0-44], p=0.27). A secondary analysis of pooled data
      documented increased time in the target range (60% [51-88] vs 40% [18-61];
      p=0.0022) and reduced time for which glucose concentrations were 3.90 mmol/L or
      lower (2.1% (0.0-10.0) vs 4.1% (0.0-42.0); p=0.0304). No events with plasma
      glucose concentration lower than 3.0 mmol/L were recorded during closed-loop
      delivery, compared with nine events during standard treatment. INTERPRETATION:
      Closed-loop systems could reduce risk of nocturnal hypoglycaemia in children and
      adolescents with type 1 diabetes. FUNDING: Juvenile Diabetes Research Foundation;
      European Foundation for Study of Diabetes; Medical Research Council Centre for
      Obesity and Related Metabolic Diseases; National Institute for Health Research
      Cambridge Biomedical Research Centre.

PMID- 20138358
TI  - Inducing local T cell apoptosis with anti-Fas-functionalized polymeric coatings
      fabricated via surface-initiated photopolymerizations.
AB  - Cell encapsulation has long been investigated as a means to achieve transplant
      immunoprotection as it creates a physical barrier between allograft tissue and
      host immune cells. Encapsulation with passive barrier materials alone, however,
      is generally insufficient to protect donor tissue from rejection, because small
      cytotoxic molecules produced by activated T cells can diffuse readily into the
      capsule and mediate allograft death. As a means to provide bioactive protection
      for polymeric encapsulation devices, we investigated a functionalized polymeric
      coating that mimics a natural T cell regulation pathway. T cells are regulated in
      vivo via Fas, a well-known 'death receptor,' whereby effector cells express Fas
      ligand and elicit T cell apoptosis upon binding the Fas receptor on a T cell
      surface. Anti-Fas antibodies are capable of replicating this effect and induce T
      cell apoptosis in solution. Here, an iniferter-based living radical
      polymerization was utilized to fabricate surface-anchored polymer chains
      containing poly(ethylene glycol) with covalently incorporated pendant anti-Fas
      antibody. Using this reaction mechanism, we demonstrate fabrication conditions
      that yield surface densities in excess of 1.5 ng/cm(2) of incorporated
      therapeutic, as detected by ELISA. Additionally, we show that coatings containing
      anti-Fas antibody induced significant T cell apoptosis, 21+/-2% of cells, after
      24h. Finally, the incorporation of a T cell adhesion ligand, intracellular
      adhesion molecule-1, along with anti-Fas antibody, yielded even higher levels of
      apoptosis, 34+/-1% of T cells, compared to either signal alone.

PMID- 20138359
TI  - Classification of the myelodysplastic syndrome in a national registry of recently
      diagnosed patients.
AB  - BACKGROUND: It is not known to what extent the WHO classification scheme for MDS
      has been adopted in clinical practice. METHODS: We reviewed the medical records
      of 200 newly diagnosed MDS patients enrolled in our national registry during the
      years 2006-2008 to determine the scheme used. RESULTS: Clear WHO subtypes were
      recorded for 45.0% of patients, compared to 5.5% for FAB subtypes; 28.0% had MDS
      documented but without WHO or FAB subtype, and for 22.5%, the schema was unclear.
      CONCLUSION: Although many MDS patients do not have a subtype or schema
      documented, when they do, the WHO system is widely used.

PMID- 20138360
TI  - Near-tetraploidy clone can evolve from a hyperdiploidy clone and cause resistance
      to lenalidomide and bortezomib in a multiple myeloma patient.
AB  - Aneuploidy is a very common prognostic factor in multiple myeloma (MM).
      Nonhyperdiploidy including near-tetraploidy (NT) is a poor prognostic indicator,
      compared to hyperdiploidy in multiple myeloma (MM). NT results from
      endoduplication of hypodiploidy. We report of a 55-year-old female patient
      diagnosed with advanced stage MM with hyperdiploidy and t(8;14)(q24;q32). The
      patient responded well to lenalidomide and dexamethasone for approximately 1
      year. At the time of progression, she had become unresponsive to lenalidomide and
      subsequently bortezomib, and was found to have NT and loss of choromosome 13.
      There is another reported patient who had a possible interchange from
      nonhyperdiploidy to hyperdiploidy status, however, artifact could not be ruled
      out. To our knowledge, this is the first patient in whom evolution of an abnormal
      clone from a hyperdiploidy to a NT abnormal clone has been confirmed during the
      natural course of MM. This evolution is associated with resistance to novel drugs
      and poor prognosis in MM.

PMID- 20138361
TI  - Cadmium impairs mineral and carbohydrate mobilization during the germination of
      bean seeds.
AB  - The germination rate, mineral (Ca, Fe, K, Mn) and carbohydrate (starch, soluble
      sugars, sucrose, glucose, fructose) contents and hydrolase activities in
      cotyledons and embryonic axes of bean seeds subjected to cadmium stress were
      investigated. Compared to the control, Cd caused a reduction in germination
      percent, embryo growth and in distribution of biomass, mineral and sugars between
      cotyledon and embryonic axis and inhibited the activities of alpha-amylase and
      invertases: soluble acid (INV-AS), soluble neutral (INV-NS), cell wall bound acid
      (INV-AW). Moreover, the solute leakage into the germination medium was also used
      as bioindicator parameter to evaluate the toxicity of cadmium accumulation, which
      increased in different tissues of germinating seeds in the duration of treatment
      and provoked nutrient loss and, thereby, electrical conductivity enhancement in
      the imbibition medium. This was correlated with an impairment of membrane
      integrity, as evidenced by high malondialdehyde (MDA) content and lipoxygenase
      (LOX) activity in Cd-poisoned embryo. The contribution of solute loss at the
      expense of growing embryonic axis to failure in reserve mobilization after Cd
      exposure is emphasized in association with the delay in seed germination.

PMID- 20138362
TI  - Evaluation of methods to determine causes of sediment toxicity in San Diego Bay,
      California, USA.
AB  - Regulation of waterbodies impaired due to sediment toxicity may require
      development of Total Maximum Daily Load (TMDL) allocations to reduce chemicals of
      concern. A key step in this process is the identification of chemicals
      responsible for toxicity, and sediment toxicity identification evaluation
      procedures (TIEs) are the primary tools used to accomplish this. Several sites in
      San Diego Bay (CA, USA) are listed as impaired due to sediment toxicity
      associated with organic chemicals and metals, and due to degraded benthic
      macroinvertebrate communities. Sediment was collected from one of these sites, at
      the confluence of Switzer Creek in San Diego Harbor. The sediment was subjected
      to selected whole-sediment TIE treatments to evaluate the efficacy of these
      procedures for identifying the causes of toxicity at Switzer Creek. Toxicity was
      assessed using the estuarine amphipod Eohaustorius estuarius. The results
      indicated that toxicity of San Diego Bay sediment was likely partly due to
      mixtures of pyrethroid pesticides. These experiments showed that the
      effectiveness of the individual TIE procedures varied by treatment. Variability
      was mainly due to inconsistency between results of samples subjected to various
      Phase II TIE procedures, including chemical analyses of samples subjected to high
      pressure liquid chromatography and direct analyses of acetone extractions of
      carbonaceous resin. The procedures require further refinement to ensure maximum
      sorption and complete elution and detection of sorbed chemicals. Despite these
      inconsistencies, the results indicate the utility of these procedures for
      identifying chemicals of concern in this system.

PMID- 20138363
TI  - Chromium(VI) is more toxic than chromium(III) to freshwater algae: a paradigm to
      revise?
AB  - The behavior and toxicity of Cr(III) and Cr(VI) to the green algae
      Pseudokirchneriella subcapitata and Chlorella kessleri were studied in a standard
      culture medium (ISO medium) and, for P. subcapitata only, in ultrafiltered
      natural water enriched with all ISO components (modified ISO medium). In all
      solutions amended with Cr(III), initial chromium concentrations decreased by 60
      90% over 72h (the duration of algal tests) indicating that protocols for testing
      poorly soluble substances are required to properly evaluate Cr(III) toxicity.
      After accounting for its behavior in test solutions, chromium(III) was 5-10 times
      more toxic than Cr(VI) in both media. For P. subcapitata, the average 72h EC50 of
      Cr(III) in ISO medium was 17.4+/-4.7 microg/L (n=9); lower than corresponding
      hardness-corrected Continuous Concentration Criteria of the US EPA and well
      within the range of Cr concentrations found in waters impacted by tannery
      discharges. These results follow from intrinsic chemical properties of Cr(III) in
      circumneutral solutions, so that the actual toxicity of Cr(III) to aquatic
      organisms may be generally underestimated.

PMID- 20138364
TI  - Establishment and characterization of dengue virus type 2 nonstructural protein 1
      specific T cell lines.
AB  - Immunity against dengue viruses (DENV) infection may include cellular immune
      responses which involve in the immunopathology of DENV infection hosts. This
      study was to establish short-term dengue virus type 2 (DENV2) nonstructural
      protein 1 (NS1) specific T cells from splenocytes from BALB/c mice immunized with
      DENV2 NS1 in vitro, which may be used to identify immunopathologic mechanism of
      dengue. Nine DENV2 NS1 specific T cell lines were successfully established by
      using limiting dilution methods and maintained for 20 weeks by re-stimulated with
      DENV2 NS1, recombinant mouse IL-2 and antigen presenting cell weekly.
      Phenotypically, these cells were mainly composed of CD3(+)CD4(+) T cells. The
      culture supernatants of these cells contained large amounts of TNF-alpha and IFN
      gamma. Vascular tissue pathological change could be found in the mice adoptive
      transferred with DENV2 NS1 specific T cells. The results indicate that DENV2 NS1
      specific T cells could be established and maintained with syngeneic T cell growth
      factors in vitro. Meanwhile, DENV2 NS1 specific T cells might contribute to the
      immunopathology of vascular leakage of dengue.

PMID- 20138365
TI  - Studies of "supported" and "supportive" housing: a comprehensive review of model
      descriptions and measurement.
AB  - Supported housing is a service model that couples provision of independent
      housing with provision of community-based supports for individuals with
      psychiatric disabilities at risk of homelessness. Despite its promise as an
      alternative to traditional sequential residential rehabilitation programs,
      supported housing has not been evaluated to an extent that supports firm
      conclusions concerning the efficacy of specific program elements. We conducted a
      comprehensive review of the literature on supported housing and similarly labeled
      programs, to determine the degree of clarity in the supported housing model and
      the degree of fidelity to that model within the empirical literature, and to
      determine whether lack of clarity or fidelity are barriers to widespread,
      systematic program implementation and evaluation. We encountered a number of
      limitations in the literature, including conflicting use of program labels,
      inconsistent definitions of supported housing and its elements, and use of
      inadequate measurement indices in assessing adherence to program elements. Our
      findings suggest that greater model clarity, better specification of model
      elements, and greater standardization in measurement of program dimensions would
      aid in supported housing program implementation and evaluation. We present a
      number of recommendations for the field and suggestions for future research.

PMID- 20138366
TI  - Evaluation of program performance and expenditures in a report of performance
      measures (RPM) via a case study of two Florida county tuberculosis programs.
AB  - Health Department (HD) managers at both state and local levels are in desperate
      need of tools to assist in monitoring and evaluating programs. The purpose of
      this study is to assess the feasibility and utility of linking program
      performance scores and expenditures into a Report of Performance Measures (RPM).
      We analyzed secondary data on performance indicators, selected by HD staff, and
      expenditures, related to six surveillance activities, from two, similar, high
      incidence, tuberculosis (TB) programs in Florida from 2002 to 2003. We compared
      the findings between the county HDs as an illustration of basic cost
      effectiveness benchmarking, based on the cost-effectiveness grid. Data included
      here provide examples of: (1) two instances in which one county was operating
      relatively inefficiently compared to the other; (2) two instances in which
      performance and expenditures were similar for the counties; and (3) two instances
      in which one county spent more for higher performance scores than the other.
      These data illustrate how the RPM can be used to facilitate benchmarking, a basic
      evaluation tool. They also demonstrate ways to identify potential operational
      inefficiencies in a single time period and ultimately over time. It is thus
      likely to be a feasible and useful management tool.

PMID- 20138367
TI  - Anti-inflammatory actions of Syk inhibitors in macrophages involve non-specific
      inhibition of toll-like receptors-mediated JNK signaling pathway.
AB  - Toll-like receptors (TLRs) are a major family of pattern recognition receptors
      (PRRs) and play a crucial role in innate immune system. Even though non-receptor
      spleen tyrosine kinase (Syk) is a key signaling molecule of immunoreceptor
      tyrosine-based activation motifs-containing immunoreceptors, its role in TLRs
      signaling is not clearly understood. Herein, we investigated the role of Syk in
      TLR-mediated signaling and gene regulation. In bone marrow-derived macrophages
      (BMDMs) and RAW 264.7 macrophages, treatment of poly(I:C), LPS and CpG, which are
      specific ligands of TLR3, TLR4 and TLR9, respectively, can increase the mRNA
      levels of several pro-inflammatory cytokines and mediators, including IFNbeta,
      TNFalpha, MIP2, IL-6, IL-12beta, iNOS and COX-2. The gene upregulation caused by
      TLR was inhibited by Syk inhibitor (SykI) and JNK inhibitor (SP600125).
      Accordingly we found the abilities of TLR3, TLR4 and TLR9 ligands to induce Syk
      and JNK activation, as evidenced by increased Syk autophosphorylation on
      Y519/Y520, JNK phosphorylation and both kinase activities. We also found that
      TLRs-mediated JNK activation, but not IKK, p38 and ERK activation as well as
      IkappaB degradation in BMDM and RAW 264.7 cells, was blocked by SykI.
      Nevertheless TLR-mediated JNK activation as well as the increased protein
      expression of iNOS and COX-2 remained unchanged when Syk protein was knockdown by
      siRNA approach. With in vitro kinase assay we found two commercial Syk inhibitors
      (SykI, and BAY61-3606) have direct inhibition on JNK activity. These findings
      demonstrate that the non-selective action of SykI on JNK should be taken into
      consideration upon using them to explore the biological actions of Syk.

PMID- 20138368
TI  - A placebo-controlled trial of microplasmin intravitreous injection to facilitate
      posterior vitreous detachment before vitrectomy.
AB  - PURPOSE: To evaluate the safety and efficacy of a preoperative intravitreous
      injection of microplasmin in patients scheduled for vitreous surgery. DESIGN:
      Phase 2, multicenter, placebo-controlled, double-masked, parallel-group, dose
      ranging clinical trial. PARTICIPANTS: One hundred twenty-five patients scheduled
      for pars plana vitrectomy (PPV), primarily for treatment of either vitreomacular
      traction or macular hole. INTERVENTION: A single intravitreous injection of
      either microplasmin at 1 of 3 doses (25 microg, 75 microg, or 125 microg in 100
      microl) or placebo injection administered 7 days before PPV. MAIN OUTCOME
      MEASURES: Presence or absence of posterior vitreous detachment (PVD) at the time
      of PPV, progression of PVD, and resolution of vitreomacular interface abnormality
      precluding the need for PPV. RESULTS: Rates of total PVD at the time of surgery
      were 10%, 14%, 18%, and 31% in the placebo group (n = 30), 25-microg (n = 29), 75
      microg (n = 33), and 125-microg microplasmin groups (n = 32), respectively. The
      secondary end point resolution of vitreomacular interface abnormality precluding
      the need for vitrectomy at the 35-day time point was observed at rates of 3%,
      10%, 15%, and 31% in the placebo, and the 25-microg, the 75-microg, and the 125
      microg microplasmin groups, respectively. At the 180-day time point, the
      equivalent rates were 3%, 7%, 15%, and 28%, respectively. CONCLUSIONS:
      Microplasmin injection at a dose of 125 microg led to a greater likelihood of
      induction and progression of PVD than placebo injection. Patients receiving
      microplasmin were significantly more likely not to require vitrectomy surgery.
      More definitive evaluation in phase 3 clinical trials therefore is warranted.
      FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after
      the references.

PMID- 20138369
TI  - Corneal biomechanical metrics and anterior segment parameters in mild
      keratoconus.
AB  - PURPOSE: To compare corneal hysteresis (CH), corneal resistance factor (CRF),
      spherical equivalent (SE), average central keratometry (K-Avg), corneal
      astigmatism (CA), corneal volume (CV), anterior chamber (AC) depth, and central
      corneal thickness (CCT) between patients with mild keratoconus and healthy
      controls and to estimate the sensitivity and specificity of CH and CRF in
      discriminating mild keratoconus from healthy corneas. DESIGN: Comparative case
      series. PARTICIPANTS: Sixty-three eyes (40 patients) with mild keratoconus (group
      1) and 80 eyes from 40 gender- and age-matched controls (group 2). METHODS:
      Patients underwent a complete clinical eye examination, corneal topography
      (Humphrey ATLAS; Carl Zeiss Meditec, Dublin, CA), tomography (Pentacam; Oculus,
      Wetzlar, Germany), and biomechanical evaluations (ocular response analyzer;
      Reichert Ophthalmic Instruments, Depew, NY). The receiver operating
      characteristic (ROC) curve was used to identify cutoff points that maximized
      sensitivity and specificity in discriminating mild keratoconus from normal
      corneas. MAIN OUTCOME MEASURES: Corneal hysteresis, CRF, SE, K-Avg, CA, CV, AC
      depth, and CCT. The diagnostic performance of CH and CRF for detecting mild
      keratoconus was assessed using the ROC curve. RESULTS: In group 1 versus group 2,
      the SE values (mean+/-standard deviation) were -3.55+/-2.87 diopters (D) versus 
      1.46+/-3.09 D (P = 0); K-Avg, 45.09+/-2.24 versus 43.24+/-1.54 D (P = 0); CA,
      3.15+/-1.87 versus 1.07+/-0.83 D (P = 0); CV, 57.3+/-2.12 versus 60.86+/-3.39 mm3
      (P = 0); AC depth, 3.19+/-0.35 versus 3.05+/-0.43 mm (P = 0.0416); CCT, 503+/
      34.15 versus 544.71+/-35.89 microm (P = 0); CH, 8.50+/-1.36 versus 10.17+/-1.79
      mmHg (P = 0); CRF, 7.85+/-1.49 versus 10.13+/-2.0 mmHg (P = 0). The ROC curve
      analyses showed a poor overall predictive accuracy of CH (cutoff, 9.64 mmHg;
      sensitivity, 87%; specificity, 65%; test accuracy, 74.83%) and CRF (cutoff, 9.60
      mmHg; sensitivity, 90.5%; specificity, 66%; test accuracy, 76.97%) for detecting
      mild keratoconus. CONCLUSIONS: The values for CH, CRF, CV, and CCT were
      statistically lower and those for SE, K-Avg, CA, and AC depth were statistically
      higher in patients with mild keratoconus compared with controls. Corneal
      hysteresis and CRF were poor parameters for discriminating between mild
      keratoconus and normal corneas. FINANCIAL DISCLOSURE(S): Proprietary or
      commercial disclosure may be found after the references.

PMID- 20138370
TI  - The role of cognitive impairment in general functioning in major depression.
AB  - The association between cognitive performance and general functioning in
      depression is controversial. The present study evaluated the association between
      cognitive dysfunction and major depressive disorder (MDD, N=70) as compared with
      age- and gender-matched healthy controls (n=206) and its relationship to general
      functioning (physical and mental health quality of life, activities of daily
      living, and employment status) in participants with current MDD (n=26) and those
      with previous MDD only (n=44). Participants were assessed clinically using the
      Mini International Neuropsychiatric Interview (M.I.N.I.) for the depression
      groups and the Diagnostic Interview for Psychoses (DIP-DM) for the control group.
      Measures to evaluate cognition and quality of lifes comprised the Repeatable
      Battery for the Assessment of Neuropsychological Status (RBANS), the Short Form
      36 Health Survey Questionnaire, and the Activities/Instrumental Activities of
      Daily Living (ADL/IADL); employment status was also assessed in MDD. The results
      showed that a) while individuals with current depression had worse cognitive
      performance in all domains than healthy controls, those individuals with previous
      depression had lasting cognitive impairments in the domains of immediate memory
      and attention as compared with healthy controls; b) individuals with current
      depression had lower scores in the visuospatial/constructional and attention
      domains and the total score than individuals with previous depression; c)
      individuals in the depression group as a whole who were currently unemployed had
      significantly lower scores in all domains (except attention) of cognitive
      function; d) cognitive function was not related to either physical or mental
      quality of life or impairments of activities of daily living (ADL, IADL); e) that
      unemployment in previous depression was related to poor cognitive function
      similar to those with current depression. The results indicate that MDD may have
      detrimental and lasting effects on cognitive performance partly related to poorer
      general functioning.

PMID- 20138371
TI  - Disentangling the attentional deficit in schizophrenia: pointers from schizotypy.
AB  - It has been argued that schizophrenia is associated with abnormalities in the
      allocation of attention, and that such abnormalities extend to members of the
      healthy population who are high in schizotypy; however, alternative
      interpretations of previous experimental evidence relating to this issue are
      possible. We present a learned irrelevance paradigm that provides a less
      equivocal measure of attentional processing during learning, and demonstrate a
      reliable reduction in learned irrelevance among healthy participants with high
      scores on a dimension of schizotypy corresponding to the positive symptoms of
      schizophrenia. These results support the suggestion that high schizotypy (and, by
      extension, schizophrenia) is associated with deficits in the appropriate
      allocation of attention.

PMID- 20138372
TI  - The effect of viewpoint on visual stimuli: a study of episodic memory in
      schizophrenia.
AB  - In everyday life, objects are rarely perceived in the exact same position as they
      were the first time. This change of position alters the perceptual viewpoint
      influencing the likelihood of recognizing the object - the similarity effect.
      Moreover, this effect may be a contributing factor to the overall episodic memory
      deficits that are apparent in people with schizophrenia. The present study
      investigated the influence of viewpoint on memory recognition in 43 schizophrenia
      and 23 healthy comparison participants. Photos of target objects were presented
      during the encoding phase alone and then during the recognition phase (as an old
      object) along with never-before presented objects. The old objects, however, now
      appeared either from the same viewpoint (unaltered condition) or from a different
      viewpoint (altered condition). Participants performed an old/new discrimination
      task during the recognition phase. Results, for both groups, revealed better
      recognition performance when the viewpoint was unaltered; that is, memory
      recognition was sensitive to viewpoint manipulation. There was no significant
      interaction however, between this similarity effect and group. Thus, visual
      functions solicited by changing the viewpoint, as well as the influence on the
      encoding and the subsequent memory retrieval, are likely intact in people with
      schizophrenia.

PMID- 20138373
TI  - Milk supplemented with immune colostrum: protection against rotavirus diarrhea
      and modulatory effect on the systemic and mucosal antibody responses in calves
      experimentally challenged with bovine rotavirus.
AB  - Group A bovine rotavirus (BRV) is the major cause of neonatal calf diarrhea
      worldwide. As a preventive strategy, we evaluated the protection and
      immunomodulation in two groups of BRV-inoculated calves. All calves received
      control colostrum (CC; VN=65,536; IgG(1)=16,384) prior to gut closure followed by
      the milk supplemented with immune colostrum (VN=1,048,576; IgG(1)=262,144), twice
      a day, for 14 days. Calves received milk supplemented with 0.8% immune colostrum
      [(Gp 1) VN=16,384; IgG(1)=4096] or milk supplemented with 0.4% immune colostrum
      [(Gp 2) VN=1024; IgG(1)=1024]. Calves receiving CC or colostrum deprived calves
      (CD) fed antibody (Ab) free milk served as controls (Gp 3 and 4). Calves were
      inoculated with virulent BRV IND at 2 days of age. Group 1 calves (milk IgG(1)
      4096) showed 80% protection against BRV diarrhea and significantly reduced virus
      shedding. At 21 post-inoculation days (PID), the antibody secreting cell (ASC)
      responses of Gp 1 calves were limited mainly to duodenal and jejunal lamina
      propria (LP) with limited or no responses in systemic sites (spleen and PBL) and
      mesenteric lymph nodes. The profile of serum and fecal Ab responses as well as
      the ASC responses was also modulated by the presence of passive IgG(1) Abs and
      probably other colostrum components, toward higher titers of IgA Ab in serum and
      feces and a greater number of IgA ASC in the proximal intestine, reflecting
      positive modulation by colostrum toward this isotype associated with optimal
      protection of the intestinal mucosa. After challenge, at PID 21, all calves in Gp
      1 and 2 were fully protected against diarrhea and only 1 of 5 calves in Gp 1 shed
      virus asymptomatically, indicating that the passive Ab treatment for 14 days was
      effective in protecting most of the animals after a first and a second virus
      exposure. The final outcome was a positive modulation of the mucosal immune
      responses and a high protection rate against diarrhea and virus shedding during
      the period of peak susceptibility to BRV infection.

PMID- 20138374
TI  - The TLR7 agonist, imiquimod, increases IFN-beta production and reduces the
      severity of experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a well-characterised model of
      autoimmune inflammatory demyelination. Toll-like receptors (TLRs) recognise
      microbial components and initiate innate immune responses. We report in this
      study that TLR7 stimulation by imiquimod, a synthetic analog of ssRNA, suppresses
      disease severity in a chronic EAE model. Disease suppression is associated with
      increased IFN-beta production in spleens of mice treated with imiquimod. In vitro
      experiments on pDCs, which express high levels of TLR7 and are potent producers
      of IFN-beta, suggest that an amplification loop involving TLR7 and IFNAR is
      required for the observed effects.

PMID- 20138375
TI  - Structural dynamics of dendritic spines in memory and cognition.
AB  - Recent studies show that dendritic spines are dynamic structures. Their rapid
      creation, destruction and shape-changing are essential for short- and long-term
      plasticity at excitatory synapses on pyramidal neurons in the cerebral cortex.
      The onset of long-term potentiation, spine-volume growth and an increase in
      receptor trafficking are coincident, enabling a 'functional readout' of spine
      structure that links the age, size, strength and lifetime of a synapse. Spine
      dynamics are also implicated in long-term memory and cognition: intrinsic
      fluctuations in volume can explain synapse maintenance over long periods, and
      rapid, activity-triggered plasticity can relate directly to cognitive processes.
      Thus, spine dynamics are cellular phenomena with important implications for
      cognition and memory. Furthermore, impaired spine dynamics can cause psychiatric
      and neurodevelopmental disorders.

PMID- 20138376
TI  - Home management of hematological patients requiring hospital admission.
AB  - The hospital-at-home service (HHS) could be considered as an alternative to the
      traditional ward for elderly patients. We aimed at evaluating the home management
      of elderly people requiring transfusions. The ever-increasing demand on acute
      hospital services requires alternative methods of delivering all aspects of
      health care. HHS demonstrated to be as efficacious as a traditional ward for
      elderly and functionally compromised patients. The method was a retrospective
      descriptive study enrolling patients needing an hospital admission from 1st
      January 2007 to 31st December 2007 and reporting an hematological discharge's
      diagnosis as primary or secondary diagnosis. A total of 54 patients were
      evaluated in this study. Of them, 34 (62.9%) needed a hemocomponent transfusion
      for a total volume of 112 blood units and 49 platelet pools. Patients requiring
      at least one blood or platelet transfusion were more functionally compromised and
      presented a higher level of acute physiology and chronic health evaluation,
      compared to the non-transfused ones. The conclusion was that hematological
      subjects mainly the frail ones and functionally highly compromised with acute
      illnesses could be treated at home as an alternative of the traditional medical
      ward. This could be the starting point for future studies that will be able to
      increase the power of hospital-at-home service for this type of patients.

PMID- 20138377
TI  - The CID Chrono cobalt-chromium alloy carbofilm-coated coronary stent system.
AB  - BACKGROUND: In an attempt to improve the stent's safety, development of bare
      metal stents (BMS) continues, with new materials and geometry. Chrono (CID,
      Italy) is a thin strut cobalt-chromium (Co-Cr) stent combining the clinical
      benefits of the bio- and haemo-compatible Carbofilm coating. METHODS: We assessed
      the safety and efficacy of percutaneous coronary interventions (PCI) using the
      new Co-Cr Chrono stent in patients undergoing elective PCI for de novo lesions in
      native coronary vessels. The patients were followed for 12 months for the
      occurrence of major cardiac events (MACE, defined as death, myocardial
      infarction, repeat PCI and bypass surgery). Patients with complex (B2/C) lesions
      were compared to those with non-complex lesions (A/B1). RESULTS: A total of 340
      consecutive patients were analysed: 155 patients with complex lesions (Complex
      group) and 185 patients with non-complex lesions (Non-complex group). Dual
      antiplatelet therapy was maintained >1 month in 21% of patients in both Complex
      and Non-complex group. Stent length was longer in the Complex group (25 +/- 10 mm
      versus 17 +/- 6 mm; p<0.001). Stent diameter <3.0 mm was most frequent in the
      Complex group (35.5% versus 27.5%; p<0.05). During the 12-month follow-up period
      MACE occurred in 10.6% of the global population (12.3% in the Complex group and
      9.2% in the Non-complex group; p=0.43). Repeat PCI was most frequent in the
      Complex group (9.7% versus 3.8%; p=0.044). The incidence of definite and probable
      stent thrombosis (ARC criteria) was 1.29% in the Complex group and 1.08% in the
      Non-complex group (p=1.0). CONCLUSIONS: Implantation of the Co-Cr Chrono stent
      results in a good safety and efficacy for both complex and non-complex de-novo
      coronary artery lesions.

PMID- 20138378
TI  - Renal dysfunction and high levels of hsCRP are additively associated with hard
      endpoints after percutaneous coronary intervention with drug eluting stents.
AB  - BACKGROUND: Chronic kidney disease (CKD) and high C-reactive protein (CRP) are
      known risk factors of cardiovascular disease. In the drug eluting stent (DES)
      era, the relationship among CKD, CRP, and long-term outcomes after percutaneous
      coronary intervention (PCI) has not yet been demonstrated. We investigated the
      combined effects of renal dysfunction and CRP on outcomes in patients who
      underwent PCI using DES. METHODS: A total of 1859 patients (mean age 64 +/- 10
      years) who underwent PCI with DES between February 2003 and June 2006, were
      divided into 4 groups (quartile) according to estimated glomerular filtration
      rate (eGFR) and hsCRP at admission. RESULTS: The composite of cumulative death
      and non-fatal myocardial infarction (mortality+MI) during median follow-up of 27
      months, was significantly higher in the lowest eGFR quartile than in the other
      three groups (hazard ratio (HR) for mortality+MI: 3.32, 95% CI: 2.21-5.00,
      P<0.001). Mortality+MI was also significantly higher in the highest hsCRP
      quartile (HR: 3.29, 95% CI: 2.02-5.37, P<0.001). A combined analysis of
      mortality+MI on the basis of hsCRP and renal function showed the exaggerated
      hazard in the combined worst quartile of hsCRP and GFR (HR of the combined worst
      quartile, 10.876, 95% CI: 3.74-31.63, P<0.001). Furthermore, both the lowest eGFR
      quartile and the highest hsCRP quartile were significantly associated with
      increased risk of stent thrombosis. In a multivariate analysis, low GFR and high
      hsCRP were independent predictors of mortality+MI after PCI with DES along with
      left ventricular dysfunction, diabetes, and left main disease. CONCLUSIONS: In an
      unselected cohort of patients receiving PCI with DES, poor renal function and
      high hsCRP were additively associated with a higher risk of hard endpoints and
      were independent predictors of mortality+MI even after correction for other
      factors. Our data suggest the importance of systemic factors on mortality even in
      the DES era.

PMID- 20138379
TI  - Clinical performance of a transmission detector array for the permanent
      supervision of IMRT deliveries.
AB  - BACKGROUND AND PURPOSE: Clinical evaluation of a novel dosimetric accessory
      serving the permanent supervision of MLC function. MATERIALS AND METHODS: The
      DAVID system (PTW-Freiburg, Germany) is a transparent, multi-wire transmission
      ionization chamber, placed in the accessory holder of the treatment head. Since
      each of the 37 individual wires is positioned exactly below the associated leaf
      pair of the MLC, its signal records the opening of this leaf pair during patient
      treatment. RESULTS: The DAVID system closes a gap in the quality assurance
      program, permitting the permanent in-vivo verification of IMRT plans. During
      dosimetric plan verification with the 2D-ARRAY (PTW-Freiburg, Germany), reference
      values of the 37 DAVID signals are collected, with which the DAVID readings
      recorded during daily patient treatment are compared. This comparison is visually
      displayed in the control room, and warning and alarm levels of any discrepancies
      can be defined. The properties of the DAVID system as a transmission device, its
      sensitivity to beam delivery and leaflet errors as well as its stability have
      been analyzed for clinically relevant examples. In a recent version, the DAVID
      system has been equipped with 80 wires. CONCLUSIONS: The DAVID system permits the
      on-line detection of clinically relevant MLC discrepancies in IMRT deliveries.

PMID- 20138380
TI  - From point A to the sculpted pear: MR image guidance significantly improves
      tumour dose and sparing of organs at risk in brachytherapy of cervical cancer.
AB  - BACKGROUND AND PURPOSE: Brachytherapy in locally advanced cervical cancer is
      still widely based on 2D standard dose planning, although 3D image guidance is
      available. The purpose of this study was to compare point doses to 3D dose volume
      parameters for tumour and organs at risk (OARs), and to evaluate the improvement
      of dose parameters with MR image guided adaptive brachytherapy (IGABT). MATERIAL
      AND METHODS: MRI-based IGABT was performed in 72 consecutive patients. HR-CTV, IR
      CTV, bladder, rectum and sigmoid were contoured according to GEC-ESTRO
      recommendations. BT standard dose planning was compared to MRI-based dose
      optimisation. RESULTS: HR-CTV dose (D90) was highly variable in standard plans
      with point A dose prescription. In small tumours (<31 cc) HR-CTV was well covered
      by standard plans in 94% of patients, while OAR constraints were exceeded in 72%
      of patients. Optimisation decreased violation of OAR constraints to only 6% of
      patients while maintaining excellent target coverage. In large tumours (>31 cc)
      the dose optimisation improved the HR-CTV D90 by a mean of 7 Gy resulting in full
      coverage in 72% of patients as compared to 25% for standard plans, even while
      reducing violation of OAR constraints. CONCLUSION: Point A dose is a poor
      surrogate of HR-CTV dose, and the use of 3D image-based dose planning is
      encouraged. MRI-based IGABT significantly improves target coverage and OAR dose.

PMID- 20138381
TI  - Stereotactic radiation therapy for large vestibular schwannomas.
AB  - BACKGROUND AND PURPOSE: To evaluate the morbidity and tumor-control rate in the
      treatment of large vestibular schwannomas (VS) after stereotactic radiation
      therapy in our institution. MATERIAL AND METHODS: Twenty-five consecutive
      patients (17 men, 8 women) with large VS (diameter 3.0 cm or larger), treated
      with stereotactic radiotherapy (SRT) or stereotactic radiosurgery (SRS) between
      1992 and 2007, were retrospectively studied after a mean follow-up period of
      three years with respect to tumor-control rate and complications. RESULTS:
      Actuarial 5-year maintenance of pre-treatment hearing level probability of 30%
      was achieved. Five of 17 patients suffered permanent new facial nerve
      dysfunction. The actuarial 5-year facial nerve preservation probability was 80%.
      Permanent new trigeminal nerve neuropathy occurred in two of 15 patients,
      resulting in an actuarial 5-year trigeminal nerve preservation probability of
      85%. Tumor progression occurred in four of 25 (16%) patients. The overall 5-year
      tumor control probability was 82%. CONCLUSION: Increased morbidity rates were
      found in patients with large VS treated with SRT or SRS compared to the published
      series on regular sized VS and other smaller retrospective studies on large VS.

PMID- 20138382
TI  - Antimicrobial activities of tapioca starch/decolorized hsian-tsao leaf gum
      coatings containing green tea extracts in fruit-based salads, romaine hearts and
      pork slices.
AB  - The antimicrobial activities of edible coatings based on a tapioca
      starch/decolorized hsian-tsao leaf gum (dHG) matrix with various green tea
      extracts (GTEs) were evaluated. Its effect on the shelf-life extension of fruit
      based salads, romaine hearts, and pork slices were investigated as well. Three
      types of GTEs from hot water (80 degrees C) (W), 40% (E4) and 80% (E8) ethanol
      were prepared. It was found that all GTEs showed pronounced inhibition on Gram
      positive bacteria in agar media, including Staphylococcus aureus BCRC 10781,
      Bacillus cereus BCRC 11778 and Listeria monocytogenes BCRC 14848, but not on Gram
      negative bacteria, such as Escherichia coli DH10beta and Salmonella enteria BCRC
      10747. The antimicrobial activities increased with increasing GTEs concentration
      (1, 2 and 5%), but did not differentiate significantly in terms of the effect of
      extraction solvents. When various GTEs (1%) were added to an edible coating
      formulation based on 1.35% tapioca starch +0.15% dHG +0.225% glycerol, pronounced
      antimicrobial activity on Gram positive bacteria was also observed as evaluated
      by using cylinder diffusion and antimicrobial migration tests. It was believed
      that the active compounds in green tea extracts could leave the coating matrix
      and migrate to increase the non-growth area. When being sprayed on various real
      food models, all tapioca starch/dHG coatings containing GTEs could successfully
      reduce the aerobic counting and growth of yeasts/molds by 1 to 2 log cycles in
      fruit-based salads, as compared to the control sample. Furthermore, during
      refrigerated storage of romaine hearts and pork slices for 48h, tapioca
      starch/dHG coatings with E4 extracts demonstrated pronounced antimicrobial
      activity against Gram positive bacteria (4-6 log cycles reduction), followed by W
      extracts and E8 extracts in a decreasing order. Such results implied the high
      efficacy of antimicrobial migration of tapioca starch/dHG coatings containing
      GTEs and their application potentials on foods.

PMID- 20138383
TI  - Type 2 diabetes mellitus impairs bone healing of dental implants in GK rats.
AB  - Type 2 diabetes is an increasingly prevalent disease with oral health
      manifestations. In this study, titanium implants were placed in the femora of 10
      type 2 diabetic and 10 age-matched normal rats. We compared the results of bone
      histomorphometry around the dental implants at 4 and 8 weeks postsurgery.

PMID- 20138384
TI  - Prescription of physical activity is not sufficient to change sedentary behavior
      and improve glycemic control in type 2 diabetes patients.
AB  - OBJECTIVE: To assess the impact of personalized exercise prescription on habitual
      physical activity and glycemic control in sedentary, insulin treated type 2
      diabetes patients during a 2-y intervention period. RESEARCH DESIGN AND METHODS:
      74 patients were randomized to the intervention (n=38) or control (n=36) group.
      The intervention group was stimulated to increase daily physical activity through
      regular, structured, and personalized exercise prescription by a physical
      therapist over the 2-y intervention period. RESULTS: Physical activity levels at
      work or in leisure time were not modulated by the exercise prescription
      intervention. In accordance, no changes in body composition, glycemic control,
      medication use or risk factors for cardiovascular disease were observed.
      CONCLUSIONS: Long-term behavioral intervention programs, providing individualized
      exercise prescription, are not sufficient to change sedentary behavior and/or
      improve glycemic control in insulin treated, type 2 diabetes patients.

PMID- 20138385
TI  - Vouchers as demand side financing instruments for health care: a review of the
      Bangladesh maternal voucher scheme.
AB  - OBJECTIVES: Demand side financing (DSF) mechanisms transfer purchasing power to
      specified groups for defined goods and services in order to increase access to
      specified services. This is an important innovation in health care systems where
      access remains poor despite substantial subsidies towards the supply side. In
      Bangladesh, a maternal health DSF pilot in 33 sub-districts was launched in 2007.
      We report the results of a rapid review of this scheme undertaken during 2008
      after 1 year of its setup. METHODS: Quantitative data collected by DSF
      committees, facilities and national information systems were assessed alongside
      qualitative data, i.e. key informant interviews and focus group discussions with
      beneficiaries and health service providers on the operation of the scheme in 6
      sub-districts. RESULTS: The scheme provides vouchers to women distributed by
      health workers that entitle mainly poor women to receive skilled care at home or
      a facility and also provide payments for transport and food. After initial
      setbacks voucher distribution rose quickly. The data also suggest that the rise
      in facility based delivery appeared to be more rapid in DSF than in other non-DSF
      areas, although the methods do not allow for a strict causal attribution as there
      might be co-founding effects. Fears that the financial incentives for surgical
      delivery would lead to an over emphasis on Caesarean section appear to be
      unfounded although the trends need further monitoring. DSF provides substantial
      additional funding to facilities but remains complex to administer, requiring a
      parallel administrative mechanism putting additional work burden on the health
      workers. There is little evidence that the mechanism encourages competition due
      to the limited provision of health care services. CONCLUSIONS: The main question
      outstanding is whether the achievements of the DSF scheme could be achieved more
      efficiently by adapting the regular government funding rather than creating an
      entirely new mechanism. Also, improving the quality of health care services
      cannot be expected by the DSF mechanism alone within an environment lacking the
      pre-requirements for competition. Quality assurance mechanisms need to be put in
      place. A large-scale impact evaluation is currently underway.

PMID- 20138386
TI  - Automatic diagnosis of vocal fold paresis by employing phonovibrogram features
      and machine learning methods.
AB  - The clinical diagnosis of voice disorders is based on examination of the rapidly
      moving vocal folds during phonation (f0: 80-300Hz) with state-of-the-art
      endoscopic high-speed cameras. Commonly, analysis is performed in a subjective
      and time-consuming manner via slow-motion video playback and exhibits low inter-
      and intra-rater reliability. In this study an objective method to overcome this
      drawback is presented being based on Phonovibrography, a novel image analysis
      technique. For a collective of 45 normophonic and paralytic voices the laryngeal
      dynamics were captured by specialized Phonovibrogram features and analyzed with
      different machine learning algorithms. Classification accuracies reached 93% for
      2-class and 73% for 3-class discrimination. The results were validated by
      subjective expert ratings given the same diagnostic criteria. The automatic
      Phonovibrogram analysis approach exceeded the experienced raters' classifications
      by 9%. The presented method holds a lot of potential for providing reliable vocal
      fold diagnosis support in the future.

PMID- 20138387
TI  - Human umbilical cord matrix-derived stem cells expressing interferon-beta gene
      significantly attenuate bronchioloalveolar carcinoma xenografts in SCID mice.
AB  - Mesenchymal stem cells derived from the human umbilical cord matrix (hUCMSCs)
      have great potential for therapeutic use for multiple diseases. The strategy that
      uses therapeutic gene-transfected hUCMSCs as cellular vehicles for targeted
      biologic agent delivery has solved the problem of short half-life or excessive
      toxicity of biological agent(s) in vivo. Interferon-beta (IFN-beta) has
      demonstrated a potent antitumor effect on many types of cancer cell lines in
      vivo. The aim of this study was to determine the anti-cancer effect of IFN-beta
      gene-transfected hUCMSCs (IFN-beta-hUCMSCs) on cells derived from
      bronchioloalveolar carcinoma, a subset of lung adenocarcinoma that is difficult
      to treat. The co-culture of a small number of IFN-beta-hUCMSCs with the human
      bronchioloalveolar carcinoma cell lines H358 or SW1573 significantly inhibited
      growth of both types of carcinoma cell lines. The culture medium conditioned by
      these cells also significantly attenuated the growth of both carcinoma cells, but
      this attenuation was abolished by adding anti-IFN-beta antibody. Finally,
      systemic administration of IFN-beta-hUCMSCs through the tail vein markedly
      attenuated growth of orthotopic H358 bronchioloalveolar carcinoma xenografts in
      SCID mice by increasing apoptosis. These results clearly indicate that IFN-beta
      hUCMSCs caused cell death of bronchioloalveolar carcinoma cells through IFN-beta
      production, thereby attenuating tumor growth in vivo. These results indicate that
      IFN-beta-hUCMSCs are a powerful anti-cancer cytotherapeutic tool for
      bronchioloalveolar carcinoma.

PMID- 20138388
TI  - Meeting report: 2nd meeting of the European Thoracic Oncology Platform (ETOP).

PMID- 20138389
TI  - Belotecan for relapsing small-cell lung cancer patients initially treated with an
      irinotecan-containing chemotherapy: a phase II trial.
AB  - BACKGROUND: Belotecan is a topoisomerase I inhibitor. This phase II trial was
      conducted to evaluate the efficacy and toxicity of belotecan in relapsing small
      cell lung cancer (SCLC) patients after irinotecan failure. PATIENTS AND METHODS:
      SCLC patients, who had relapsed at least 3 months after achieving objective
      response to irinotecan plus platinum chemotherapy, were eligible. Belotecan was
      administered at a dose of 0.5 mg/m(2)/day for 5 consecutive days every 3 weeks.
      RESULTS: Twenty-seven patients were enrolled in this study. Twenty-five patients
      were evaluated for response, and 27 patients were evaluated for toxicity and
      survival. The overall response rate was 22%. The median time to progression was
      4.7 months (95% CI, 3.6-5.8 months), and the median overall survival was 13.1
      months (95% CI, 10.4-15.8 months). The most frequent grade 3/4 toxicities were
      neutropenia (93%) and thrombocytopenia (48%). There was one treatment-related
      death due to pneumonia. CONCLUSION: Belotecan showed modest activity and
      manageable toxicities in relapsing SCLC patients in this study which was
      conducted in Asia. But further study in Caucasian patients is needed.

PMID- 20138390
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis
      of lung cancer.
AB  - PURPOSE: We performed this study to evaluate the role of endobronchial ultrasound
      guided transbronchial needle aspiration (EBUS-TBNA) in the pathologic diagnosis
      of lung cancer including lung masses as well as lymph nodes as targets. METHODS:
      We retrospectively reviewed 126 patients who underwent EBUS-TBNA to diagnose
      radiologically suspected lung cancer. The patients had masses or lymph nodes that
      were highly suspicious for malignancy and accessible by EBUS-TBNA. RESULTS: EBUS
      TBNA was performed on 195 lesions (lymph nodes, n=151; lung masses, n=44). In 61
      cases, other diagnostic methods had failed previous to EBUS-TBNA. In 118
      patients, no definite endobronchial mucosal tumor invasion was observed. In eight
      patients with endobronchial tumor invasion, EBUS-TBNA was chosen due to tumor
      bleeding, necrosis, or difficult location for endobronchial biopsy. EBUS-TBNA
      confirmed 105 lung cancers, five other malignancies and six specific benign
      cases, demonstrating a diagnostic yield of 92.1% (116/126). Nine cases were
      diagnosed by other methods (lung cancer, n=2; other malignancies, n=2; benign
      cases, n=5). One case that was not confirmed by any diagnostic method was
      considered false negative. The sensitivity and diagnostic accuracy of EBUS-TBNA
      in the diagnosis of lung cancer were 97.2% (105/108) and 97.6% (123/126),
      respectively. CONCLUSIONS: EBUS-TBNA targeting lymph nodes or masses highly
      suspicious for malignancy demonstrated high diagnostic value in the diagnosis of
      lung cancer. EBUS-TBNA is recommended for these cases, especially when other
      diagnostic methods have failed or are difficult.

PMID- 20138391
TI  - Identification of different itineraries and retromer components for endosome-to
      Golgi transport of TGN38 and Shiga toxin.
AB  - The retrograde transport pathways from early/recycling endosomes are critical for
      recycling a range of endogenous cargo, as well as internalisation of bacterial
      and plant toxins. We have previously shown that the retrograde transport of the
      two model cargos, TGN38 and Shiga toxin, differs in the requirement for TGN
      golgins; transport of TGN38 requires the TGN golgin GCC88 whereas that of Shiga
      toxin requires GCC185. Here we have further defined the retrograde transport
      requirements of these two cargos. Tracking the transport of these cargos
      demonstrated that the bulk of Shiga toxin is transported from early endosomes to
      recycling endosomes en route to the TGN whereas the bulk of TGN38 is transported
      from early endosomes to the TGN with only low levels detected in recycling
      endosomes. In cells depleted of the TGN t-SNARE syntaxin 16, TGN38 accumulated
      predominantly in early endosomes whereas Shiga toxin accumulated in Rab11
      positive recycling endosomes, suggesting distinct routes for each cargo.
      Retrograde transport of Shiga toxin and TGN38 requires retromer, however, whereas
      sorting nexin 1 (SNX1) is specifically required for transport of Shiga toxin,
      sorting nexin 2 (SNX2) is required for the transport of TGN38. Overall, our data
      have identified different itineraries for the retrograde transport of Shiga toxin
      and TGN38 and distinct retromer components that regulate the transport of these
      cargos.

PMID- 20138392
TI  - Distinct functions of Mst77F and protamines in nuclear shaping and chromatin
      condensation during Drosophila spermiogenesis.
AB  - Chromatin reorganisation is a major event towards the end of mammalian and
      Drosophila spermatogenesis. In Drosophila, we previously identified protamine A,
      protamine B and Mst77F as major chromatin components of the mature sperm. Here,
      an antibody against Mst77F reveals a dual expression pattern of Mst77F as a
      chromatin component and in association with microtubules during nuclear shaping.
      Spermatids of ms(3)nc3 (Mst77F(1)) mutants show disturbed nuclear shaping,
      instability of perinuclear microtubules but no obvious chromatin condensation
      defects. Furthermore, we generated a deletion including both protamine genes
      (prot Delta) and observed that in Drosophila, protamine genes are not
      haploinsufficient in contrast to those of mice and humans. Moreover, we show that
      in prot Delta mutants, histone degradation, distribution of DNA breaks and
      Tpl(94D)-eGFP and Mst77F expression proceed as in wild-type males. Surprisingly,
      in homozygous prot Delta mutants, males are fertile and sperm are motile, while
      about 20% of sperm show abnormally shaped nuclei. The latter phenotype can be
      rescued by supplying protamine-eGFP but not by supplying Mst77F-eGFP. Finally, we
      demonstrate a 21% increase in X-ray-induced mutation rate of prot Delta sperm.
      These data support the long-standing hypothesis that the switch from a histone-
      to protamine-based chromatin protects the paternal genome from mutagens.

PMID- 20138393
TI  - Proteome study of the phloem sap of pumpkin using multidimensional protein
      identification technology.
AB  - The phloem is the major transport route for both small substances and large
      molecules, such as proteins and RNAs, from their sources to sink tissues. To
      investigate the proteins present in pumpkin phloem sap, proteome analysis using
      multidimensional protein identification technology was carried out. Pumpkin
      phloem peptides obtained by liquid chromatography/mass spectrometry/mass
      spectrometry were searched against pumpkin protein data derived from the National
      Center for Biotechnology Information. A total of 47 pumpkin phloem proteins were
      identified. The identified proteins mainly corresponded to enzymes involved in
      gibberellin biosynthesis, antioxidation processes, or defense mechanisms.
      Interestingly, seven enzymes required for gibberellin biosynthesis were
      identified for the first time by this proteomics approach. In summary, the new
      phloem proteins identified in this study provide strong evidence for stress and
      defense signaling and new insights regarding the role of gibberellin in the
      developmental programming of higher plants through the phloem.

PMID- 20138394
TI  - Atypical vascular lesion of the breast.
AB  - Atypical vascular lesions (AVLs) are vascular proliferations that develop after
      surgery and radiation for breast carcinoma and may represent precursors to
      angiosarcoma. AVLs are not well-known entities and currently lack official
      prognostic factors and guidelines for surgical treatment. We report the case of a
      patient who developed an AVL, vascular type, 4 years after lumpectomy and
      radiation therapy for ductal carcinoma in situ of the breast. The patient
      underwent wide local excision with 1-cm margins with subsequent pathologic
      examination confirming complete excision of the residual atypical vascular
      proliferation. This case highlights the importance of close cutaneous
      surveillance in patients with a history of surgery and radiation for breast
      carcinoma, and a low threshold for biopsy. More studies are needed to further
      delineate the risk of AVLs progressing to angiosarcoma and to identify histologic
      features or immunophenotypic markers, which may be predictive of this risk.
      Furthermore, formal treatment recommendations for these enigmatic entities would
      be helpful.

PMID- 20138395
TI  - Comparison of advertising strategies between the indoor tanning and tobacco
      industries.
AB  - The indoor tanning industry is large and continues to grow, with 2007 domestic
      sales in excess of $5 billion. Advertising is central to shaping the consumer's
      perception of indoor tanning as well as driving industry demand. This article
      aims to identify key drivers of consumer appeal by comparing tanning advertising
      strategies to those used by tobacco marketers. Tobacco advertising was selected
      as a reference framework because it is both well documented and designed to
      promote a product with known health hazards. Two thousand advertisements from 4
      large tobacco advertisement databases were analyzed for type of advertisement
      strategy used, and 4 advertising method categories were devised to incorporate
      the maximum number of advertisements reviewed. Subsequently, contemporary tanning
      advertisements were collected from industry magazines and salon websites and
      evaluated relative to the identified strategy profiles. Both industries have
      relied on similar advertising strategies, including mitigating health concerns,
      appealing to a sense of social acceptance, emphasizing psychotropic effects, and
      targeting specific population segments. This examination is a small observational
      study, which was conducted without rigorous statistical analysis, and which is
      limited both by the number of advertisements and by advertising strategies
      examined. Given the strong parallels between tobacco and tanning advertising
      methodologies, further consumer education and investigation into the public
      health risks of indoor tanning is needed.

PMID- 20138396
TI  - The importance of "shrinkage" in subgroup analyses.
AB  - STUDY OBJECTIVE: Subgroup analyses examine associations (eg, between treatment
      and outcome) within subsets of a larger study sample. The traditional approach
      evaluates the data in each of the subgroups independently. More accurate answers,
      however, may be expected when the rest of the data are considered in the analysis
      of each subgroup, provided there are 3 or more subgroups. METHODS: We present a
      conceptual introduction to subgroup analysis that makes use of all the available
      data and then illustrate the technique by applying it to a previously published
      study of pediatric airway management. Using WinBUGS, freely available computer
      software, we perform an empirical Bayesian analysis of the treatment effect in
      each of the subgroups. This approach corrects the original subgroup treatment
      estimates toward a weighted average treatment effect across all subjects.
      RESULTS: The revised estimates of the subgroup treatment effects demonstrate
      markedly less variability than the original estimates. Further, using these
      estimates will reduce our total expected error in parameter estimation compared
      with using the original, independent subgroup estimates. Although any particular
      estimate may be adjusted inappropriately, adopting this strategy will, on
      average, lead to results that are more accurate. CONCLUSION: When multiple
      subgroups are considered, it is often inadvisable to ignore the rest of the study
      data. Authors or readers who wish to examine associations within subgroups are
      encouraged to use techniques that reduce the total expected error.

PMID- 20138397
TI  - A prospective evaluation of emergency department bedside ultrasonography for the
      detection of acute cholecystitis.
AB  - STUDY OBJECTIVE: We assess the diagnostic accuracy of emergency physician
      performed bedside ultrasonography and radiology ultrasonography for the detection
      of cholecystitis, as determined by surgical pathology. METHODS: We conducted a
      prospective, observational study on a convenience sample of emergency department
      (ED) patients presenting with suspected cholecystitis from May 2006 to February
      2008. Bedside gallbladder ultrasonography was performed by emergency medicine
      residents and attending physicians at an academic institution. Emergency
      physicians assessed for gallstones, a sonographic Murphy's sign, gallbladder wall
      thickness, and pericholecystic fluid, and the findings were recorded before
      formal imaging. The test characteristics of bedside and radiology ultrasonography
      were determined by comparing their respective results to pathology reports and
      clinical follow-up at 2 weeks. RESULTS: Of the 193 patients enrolled, 189 were
      evaluated by bedside ultrasonography. Forty-three emergency physicians conducted
      the ultrasonography, and each physician performed a median of 2 tests. After the
      bedside ultrasonography, 125 patients received additional radiology
      ultrasonography. Twenty-six patients underwent cholecystectomy, 23 had pathology
      confirmed cholecystitis, and 163 were discharged home to follow-up. Twenty-five
      were excluded (23 lost to follow-up and 2 unavailable pathology). The test
      characteristics of bedside ultrasonography were sensitivity 87% (95% confidence
      interval [CI] 66% to 97%), specificity 82% (95% CI 74% to 88%), positive
      likelihood ratio 4.7 (95% CI 3.2 to 6.9), negative likelihood ratio 0.16 (95% CI
      0.06 to 0.46), positive predictive value 44% (95% CI 29% to 59%), and negative
      predictive value 97% (95% CI 93% to 99%). The test characteristics of radiology
      ultrasonography were sensitivity 83% (95% CI 61% to 95%), specificity 86% (95% CI
      77% to 92%), positive likelihood ratio 5.7 (95% CI 3.3 to 9.8), negative
      likelihood ratio 0.20 (95% CI 0.08 to 0.50), positive predictive value 59% (95%
      CI 41% to 76%), and negative predictive value 95% (95% CI 88% to 99%).
      CONCLUSION: The test characteristics of emergency physician-performed bedside
      ultrasonography for the detection of acute cholecystitis are similar to the test
      characteristics of radiology ultrasonography. Patients with a negative ED bedside
      ultrasonography result are unlikely to require cholecystectomy or admission for
      cholecystitis within 2 weeks of their initial presentation.

PMID- 20138398
TI  - Placing emergency care on the global agenda.
AB  - Emergency care serves a key function within health care systems by providing an
      entry point to health care and by decreasing morbidity and mortality. Although
      primarily focused on evaluation and treatment for acute conditions, emergency
      care also serves as an important locus of provision for preventive care with
      regard to injuries and disease progression. Despite its important and increasing
      role, however, emergency care has been frequently overlooked in the discussion of
      health systems and delivery platforms, particularly in developing countries.
      Little research has been done in lower- and middle-income countries on the burden
      of disease reduction attributable to emergency care, whether through injury
      treatment and prevention, urgent and emergency treatment of acute conditions, or
      emergency treatment of complications from chronic conditions. There is a critical
      need for research documenting the role of emergency care services in reducing the
      global burden of disease. In addition to applying existing methodologies toward
      this aim, new methodologies should be developed to determine the cost
      effectiveness of these interventions and how to effectively cover the costs of
      and demands for emergency care needs. These analyses could be used to emphasize
      the public health and clinical importance of emergency care within health systems
      as policymakers determine health and budgeting priorities in resource-limited
      settings.

PMID- 20138399
TI  - Coronary artery calcium scoring in the emergency department: identifying which
      patients with chest pain can be safely discharged home.
AB  - STUDY OBJECTIVE: Coronary artery calcium scoring (CACS) is a simple and readily
      available test for identifying coronary artery disease. Our objective is to
      evaluate whether a CACS of zero will identify chest pain patients who can be
      safely discharged home, without need for further cardiac testing. METHODS: This
      was a prospective observational cohort study conducted at an urban tertiary care
      hospital of stable patients presenting to the emergency department (ED) with
      chest pain of uncertain cardiac cause. Patients with a normal initial troponin
      level, nonischemic ECG, and no history of coronary artery disease had stress
      myocardial perfusion imaging (SPECT) and CACS within 24 hours of ED admission.
      Cardiac events were defined as an acute coronary syndrome during the index
      hospitalization or in follow-up. CACS results were assessed in relation to SPECT
      findings and cardiac events. RESULTS: The 1,031 patients enrolled (mean [SD] age
      54 [13] years) had a median CACS of 0 (61% with CACS of 0). The frequency of an
      abnormal SPECT ranged from 0.8% (CACS of 0) to17% (CACS>400). Cardiac events
      occurred in 32 patients (3.1%) during the index hospitalization (N=28) or after
      hospital discharge (N=4) (mean 7.4 [3.3] months). Only 2 events occurred in 625
      patients with a CACS of 0 (0.3%; 95% confidence interval 0.04% to 1.1%). Thus, 2
      of 32 patients with a cardiac event had a CACS of 0 (6%; 95% confidence interval
      0.8% to 21%). Both of these patients developed increased troponin levels during
      their index visit but had normal serial ECG and SPECT study results and no
      cardiac events at 6-month follow-up. CONCLUSION: A majority of patients (61% in
      our sample) evaluated for chest pain of uncertain cardiac cause have a CACS of 0,
      which predicts both a normal SPECT result and an excellent short-term outcome.
      Our results suggest that patients with a CACS of 0 can be discharged home,
      without further cardiac testing.

PMID- 20138400
TI  - Out-of-hospital endotracheal intubation experience and patient outcomes.
AB  - STUDY OBJECTIVE: Previous studies suggest improved patient outcomes for providers
      who perform high volumes of complex medical procedures. Out-of-hospital tracheal
      intubation is a difficult procedure. We seek to determine the association between
      rescuer procedural experience and patient survival after out-of-hospital tracheal
      intubation. METHODS: We analyzed probabilistically linked Pennsylvania statewide
      emergency medicine services, hospital discharge, and death data of patients
      receiving out-of-hospital tracheal intubation. We defined tracheal intubation
      experience as cumulative tracheal intubation during 2000 to 2005; low=1 to 10
      tracheal intubations, medium=11 to 25 tracheal intubations, high=26 to 50
      tracheal intubations, and very high=greater than 50 tracheal intubations. We
      identified survival on hospital discharge of patients intubated during 2003 to
      2005. Using generalized estimating equations, we evaluated the association
      between patient survival and out-of-hospital rescuer cumulative tracheal
      intubation experience, adjusted for clinical covariates. RESULTS: During 2003 to
      2005, 4,846 rescuers performed tracheal intubation. These individuals performed
      tracheal intubation on 33,117 patients during 2003 to 2005 and 62,586 patients
      during 2000 to 2005. Among 21,753 cardiac arrests, adjusted odds of survival was
      higher for patients intubated by rescuers with very high tracheal intubation
      experience; adjusted odds ratio (OR) versus low tracheal intubation experience:
      very high 1.48 (95% confidence interval [CI] 1.15 to 1.89), high 1.13 (95% CI
      0.98 to 1.31), and medium 1.02 (95% CI 0.91 to 1.15). Among 8,162 medical
      nonarrests, adjusted odds of survival were higher for patients intubated by
      rescuers with high and very high tracheal intubation experience; adjusted OR
      versus low tracheal intubation experience: very high 1.55 (95% CI 1.08 to 2.22),
      high 1.29 (95% CI 1.04 to 1.59), and medium 1.16 (95% CI 0.97 to 1.38). Among
      3,202 trauma nonarrests, survival was not associated with rescuer tracheal
      intubation experience; adjusted OR versus low tracheal intubation experience:
      very high 1.84 (95% CI 0.89 to 3.81), high 1.25 (95% CI 0.85 to 1.85), and medium
      0.92 (95% CI 0.67 to 1.26). CONCLUSION: Rescuer procedural experience is
      associated with improved patient survival after out-of-hospital tracheal
      intubation of cardiac arrest and medical nonarrest patients. Rescuer procedural
      experience is not associated with patient survival after out-of-hospital tracheal
      intubation of trauma nonarrest patients.

PMID- 20138401
TI  - Cardiopulmonary resuscitation interruptions with use of a load-distributing band
      device during emergency department cardiac arrest.
AB  - STUDY OBJECTIVE: Our primary aim is to measure no-flow time and no-flow ratio
      before and after an emergency department (ED) switched from manual to a load
      distributing band mechanical cardiopulmonary resuscitation (CPR) device. METHODS:
      This was a phased, before-after cohort evaluation at an urban tertiary hospital
      ED. We collected continuous video and chest compression data with the
      Physiocontrol CodeStat Suite 7.0 for resuscitations during the period just before
      and after adoption of load-distributing band CPR. All out-of-hospital,
      nontraumatic cardiac arrest, adult patients were eligible. From February 2007 to
      July 2008, there were 26 manual and 41 load-distributing band cases. RESULTS:
      Patients in both phases were comparable in terms of demographics, medical
      history, witnessed arrest, arrest location, bystander CPR rates, out-of-hospital
      defibrillation, initial rhythm, and ED defibrillation. The median no-flow time,
      defined as the sum of all pauses between compressions longer than 1.5 seconds,
      during the first 5 minutes of resuscitation, was manual CPR 85 seconds
      (interquartile range [IQR] 45 to 112 seconds) versus load-distributing band 104
      seconds (IQR 69 to 151 seconds). The mean no-flow ratio, defined as no-flow time
      divided by segment length, was manual 0.28 versus load-distributing band 0.40
      (difference=-0.12; 95% confidence interval -0.22 to -0.02). However, from 5 to 10
      minutes into the resuscitation, median no-flow time was manual 85 seconds (IQR 59
      to 151 seconds) versus load-distributing band 52 seconds (IQR 34 to 82 seconds)
      and mean no-flow ratio manual 0.34 versus load-distributing band 0.21
      (difference=0.13; 95% confidence interval 0.02 to 0.24). The average time to
      apply load-distributing band CPR during this period was 152 seconds. CONCLUSION:
      Application of a load-distributing band in the ED is associated with a higher no
      flow ratio than manual CPR in the first 5 minutes of resuscitation. We suggest
      that attention to team training, rapid application of the device to minimize
      interruption, and feedback from defibrillator and video recordings may be useful
      to improve resuscitation team performance.

PMID- 20138402
TI  - I(2)(PP2A) regulates p53 and Akt correlatively and leads the neurons to abort
      apoptosis.
AB  - A chronic neuron loss is the cardinal pathology in Alzheimer disease (AD), but it
      is still not understood why most neurons in AD brain do not accomplish apoptosis
      even though they are actually exposed to an environment with enriched
      proapoptotic factors. Protein phosphatase-2A inhibitor-2 (I(2)(PP2A)), an
      endogenous PP2A inhibitor, is significantly increased in AD brain, but the role
      of I(2)(PP2A) in AD-like neuron loss is elusive. Here, we show that I(2)(PP2A)
      regulates p53 and Akt correlatively. The mechanisms involve activated
      transcription and p38 MAPK activities. More importantly, we demonstrate that the
      simultaneous activation of Akt induced by I(2)(PP2A) counteracts the
      hyperactivated p53-induced cell apoptosis. Furthermore, I(2)(PP2A), p53 and Akt
      are all elevated in the brain of mouse model and AD patients. Our results suggest
      that the increased I(2)(PP2A) may trigger apoptosis by p53 upregulation, but due
      to simultaneous activation of Akt, the neurons are aborted from the apoptotic
      pathway. This finding contributes to the understanding of why most neurons in AD
      brain do not undergo apoptosis.

PMID- 20138403
TI  - Increased neural progenitors in vascular dementia.
AB  - Since groundbreaking studies demonstrated the presence of progenitor cells in the
      adult human brain, there have been intense interests in their potential
      therapeutic application, but to date only limited data has been obtained in man.
      An immunohistological study was performed in order to examine neurogenesis in
      both the subventricular and peri-infarct zones of vascular dementia patients
      compared to age-matched controls. The results were striking, showing a
      significant increase of progenitor cells in both the subventricular zone and in
      peri-infarct area in patients with vascular dementia compared to controls, which
      was sustained even in patients with infarcts occurring more than three months
      prior to autopsy. Moreover, the peri-infarct response appeared to be unified with
      that of the subventricular zone via a stream of cells, with some of them
      differentiating into immature neurons. We conclude that neurogenesis is
      stimulated in vascular dementia patients and, specifically, in patients with
      visible infarcts. Progenitors may migrate from the neurogenic niche to areas of
      infarction and differentiate into neurons, even three months after
      cerebrovascular damage, thus implicating the feasibility of enhancing
      neurogenesis as a novel treatment approach.

PMID- 20138404
TI  - FUS mutations in sporadic amyotrophic lateral sclerosis.
AB  - Mutations in the FUS gene have recently been described as a cause of familial
      amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of
      sporadic ALS is unclear. We undertook mutational screening of all coding exons of
      FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15
      represents a mutational hotspot, we sequenced this exon in an additional 1295
      sporadic cases. Six variants in six different cases were found, indicating that
      FUS mutations can underlie apparently sporadic ALS, but account for less than 1%
      of this form of disease.

PMID- 20138405
TI  - Changes in kinetics of amino acid uptake at the ageing ovine blood-cerebrospinal
      fluid barrier.
AB  - Amino acids (AA) in brain are precisely controlled by blood-brain barriers, which
      undergo a host of changes in both morphology and function during ageing. The
      effect of these age-related changes on AA homeostasis in brain is not well
      described. This study investigated the kinetics of four AA (Leu, Phe, Ala and
      Lys) uptakes at young and old ovine choroid plexus (CP), the blood-cerebrospinal
      fluid (CSF) barrier (BCB), and measured AA concentrations in CSF and plasma
      samples. In old sheep, the weight of lateral CP increased, so did the ratio of
      CP/brain. The expansion of the CP is consistent with clinical observation of
      thicker leptomeninges in old age. AA concentrations in old CSF, plasma and their
      ratio were different from the young. Both V(max) and K(m) of Phe and Lys were
      significant higher compared to the young, indicating higher trans-stimulation in
      old BCB. Cross-competition and kinetic inhibition studies found the sensitivity
      and specificity of these transporters were impaired in old BCB. These changes may
      be the first signs of a compromised barrier system in ageing brain leading
      increased AA influx into the brain causing neurotoxicity.

PMID- 20138406
TI  - [Variability in the measurement of the pharmaceutical prescription quality by
      autonomous communities].
AB  - AIM: To examine how the different Spanish health regions are evaluating
      pharmaceutical prescription quality and the type of prescribing indicators used.
      DESIGN: Cross-sectional study. SETTING: The 17 Spanish Autonomous Communities
      during the period from January to December 2007. MEASUREMENTS: Definition and
      type of prescribing indicators, measurement units. RESULTS: We obtained
      information from 16 of the 17 CCAA through their health services. All health
      services had developed quality indicators of drug prescription. The number of
      indicators varied from 3 to 22 between regions. Most of the regions are using
      indicators based on adequate selection of drugs. Nine of the 16 CCAA are also
      including prevalence indicators and only the Basque Country and Cantabria are
      using indicators based on the quality of the therapeutic process. Nine CCAA use
      the number of packs as measurement unit and the other seven CCAA measure
      prescriptions in defined daily doses (ddd). The indicators most frequently used
      are: percentage of new drugs in 15 CCAA (93%), omeprazole in total IBP drugs in
      13 (81.2%), percentage of generic drugs in 11 (68.7%) and selection of NSAID in
      10 (62%). CONCLUSION: Each regional health service has developed its own set of
      drug prescription quality indicators. Consequently, there is great variability
      between regions in the assessment of the quality of drug prescription. Common
      indicators are needed in order to establish a benchmarking process between
      regional health services.

PMID- 20138407
TI  - [Do we need multidisciplinary heart failure programmes in primary care?].

PMID- 20138408
TI  - [Fibrous dysplasia of the bone. Contribution of nuclear medicine in the diagnosis
      of suspicion of sarcomatous degeneration].
AB  - Fibrous dysplasia (FD) is a relatively frequent benign disease of the bone in
      which there is a maturation disorder of the bone-forming mesenchyme where the
      lamellar bone marrow is replaced with abnormal fibrous tissue. Its diagnosis is
      often an accidental finding when X-ray studies or bone scans are performed for
      other reasons since it is usually asymptomatic. There may be complications such
      as deformities, pathological fractures and exceptionally malignant
      transformation. The differential diagnosis between malignancy and FD can be
      complicated and lead to late diagnosis when sarcomatous degeneration already
      exists. In this context, the positron tomography with (18)F-fluorodeoxyglucose
      (FDG-PET) may be useful in the monitoring of this condition. We present two cases
      of patients diagnosed of FD with suspicion of malignization of their bone lesions
      who were referred to Nuclear Medicin.

PMID- 20138409
TI  - Synthesis, characterization, and biocide properties of semicarbazide-formaldehyde
      resin and its polymer metal complexes.
AB  - Semicarbazide-formaldehyde resin (SFRs) was prepared by the condensation of
      semicarbazide with formaldehyde in an acidic medium and its polymer metal
      complexes were prepared with transition metal ions. All the synthesized polymers
      were characterized by elemental analysis, FTIR, (1)H NMR, (13)C NMR, electronic
      spectroscopy, magnetic moment measurement and thermogravimetric analyses. The
      percentage of metal in all the polymer metal complexes was found to be consistent
      with 2:1 (resin: metal) stoichiometry. The magnetic susceptibility measurement
      and electronic spectra of all the polymer metal complexes confirmed the geometry
      of the complexes. All the synthesized polymeric compounds have been screened in
      vitro against Bacillus subtilis, Staphylococcus aureus (Gram-positive) and
      Escherichia coli, Salmonella typhi (Gram-negative) using shaking flask method.
      The entire polymer metal complexes showed excellent anti-bacterial activity and
      low toxicity when compared with their parental polymeric resin. The anti
      bacterial activity and toxicity of the entire synthesized compound is significant
      and they can be used as antimicrobial as well as anticancer agents for mammals in
      future.

PMID- 20138410
TI  - Moving in circles: a brief history of reports and inquiries relating to mental
      health content in undergraduate nursing curricula.
AB  - Since the abolition of specialist, undergraduate education in mental health
      nursing, serious concerns have been raised about the inadequate amount of theory
      and clinical experience devoted to this specialty in most pre-registration
      nursing programs in Australia. A number of government initiated reports and
      inquiries have been undertaken to scope the problem and provide recommendations
      with the aim of overcoming the identified deficits. Most inquiries have agreed
      that mental health nursing is under-represented in undergraduate programs and
      this has serious consequences for establishing a sustainable mental health
      nursing workforce and for providing optimal care for people experiencing a mental
      illness. The recommendations tend to support the continuation of comprehensive
      nursing education, but emphasise the need for increased mental health content.
      Terms like significant and substantial are often used which are not easily
      quantifiable. The repetitive nature of the recommendations and findings of the
      reports suggests that real change is not likely to occur unless specific minimum
      standards for the mental health content of undergraduate nursing programs are
      set.

PMID- 20138411
TI  - The supervision of professional doctorates: experiences of the processes and ways
      forward.
AB  - The doctoral research terrain is changing, as new-styles, for example
      professional doctorates, are being developed (Park, C., 2005. New variant PhDL
      the changing nature of the doctorate in the UK. Journal of Higher Education
      Policy and Management 27(2), 189-207). There is a scarcity of literature aimed at
      supervisors (Gatfield, T., 2005, An investigation into PhD supervisory management
      styles: development of a dynamic conceptual model and its managerial
      implications. Journal of Higher Education Policy and Management 27(3), 311-325)
      and this is particularly so in relation to professional doctorates. In this
      position paper we argue that the supervisory approach required for a professional
      doctorate student is different than that required for a PhD. Professional
      doctorate students, like PhD students, are required to make an explicit
      contribution to knowledge. Their emphasis, however, needs to be in producing
      knowledge that is theoretically sound, original, and of relevance to their
      practice area. This is of increasing importance within healthcare with the
      growing emphasis on patient driven translational research. As such, the students
      and their supervisors face unique challenges of balancing academic requirements
      with praxis. We suggest this requires specific tools to make explicit the
      dialogical relationship between a particular project and the cultural, social,
      educational and political aspects of its environment. We expose the potential of
      soft systems methodology as a means to highlight the emergent aspects of a
      doctoral practice development project, their respective and evolving supervisory
      interactions. This focus of this paper is therefore not about guiding supervision
      in a managerial sense, but rather at offering methodological suggestions that
      could underpin applied research at doctoral level.

PMID- 20138412
TI  - Fish oil regulates cell proliferation, protect DNA damages and decrease HER-2/neu
      and c-Myc protein expression in rat mammary carcinogenesis.
AB  - BACKGROUND & AIMS: The aim of this study is to assess the effect of dietary fish
      oil (MaxEPA) on DNA-strand breaks, cell proliferation and anti-apoptotic protein
      expressions in rat mammary carcinogenesis. METHODS: Eighty-one female Sprague
      Dawley rats were divided into two parts, one for DNA-strand breaks study and the
      other for immunohistochemical study. Female Sprague-Dawley rats were treated with
      7,12-dimethylbenz(alpha)anthracene (DMBA) (0.5 mg/0.2 ml corn oil/100 g body
      weight) by a tail vein injection. Rats were fed either fish oil or corn oil (0.5
      ml/day/rat) by oral gavage. RESULTS: Fish oil-treated group showed significant
      protection against generation of single-strand breaks (SSBs) (56.1%, P < 0.05)
      but increased effect (72.3%, P < 0.05) was found in the corn oil-treated group
      when compared to DMBA control group. Furthermore, fish oil-treated group
      exhibited substantial decrease in Ki-67 (P < 0.05), HER-2/neu (P < 0.05) and c
      Myc (P < 0.05) immunolabelling indices when compared to carcinogen counterpart.
      However, corn oil treatment resulted in significant increase in the above
      parameters. CONCLUSIONS: The above data support the role of n-3 PUFA as a
      preventive agent for DNA damages and a potential to inhibit mammary
      carcinogenesis.

PMID- 20138413
TI  - Early urinary markers of diabetic kidney disease: a nested case-control study
      from the Diabetes Control and Complications Trial (DCCT).
AB  - BACKGROUND: Urinary markers were tested as predictors of macroalbuminuria or
      microalbuminuria in patients with type 1 diabetes. STUDY DESIGN: Nested case
      control of participants in the Diabetes Control and Complications Trial (DCCT).
      SETTING & PARTICIPANTS: 87 cases of microalbuminuria were matched to 174 controls
      in a 1:2 ratio, while 4 cases were matched to 4 controls in a 1:1 ratio,
      resulting in 91 cases and 178 controls for microalbuminuria. 55 cases of
      macroalbuminuria were matched to 110 controls in a 1:2 ratio. Controls were free
      of micro-/macroalbuminuria when their matching case first developed micro
      /macroalbuminuria. PREDICTORS: Urinary N-acetyl-beta-d-glucosaminidase (NAG),
      pentosidine, advanced glycation end product (AGE) fluorescence, and albumin
      excretion rate (AER). OUTCOMES: Incident microalbuminuria (2 consecutive annual
      AERs > 40 but < or = 300 mg/d) or macroalbuminuria (AER > 300 mg/d).
      MEASUREMENTS: Stored urine samples from DCCT entry and 1-9 years later when macro
      or microalbuminuria occurred were measured for the lysosomal enzyme NAG and the
      AGE pentosidine and AGE fluorescence. AER and adjustor variables were obtained
      from the DCCT. RESULTS: Submicroalbuminuric AER levels at baseline independently
      predicted microalbuminuria (adjusted OR, 1.83; P < 0.001) and macroalbuminuria
      (adjusted OR, 1.82; P < 0.001). Baseline NAG excretion independently predicted
      macroalbuminuria (adjusted OR, 2.26; P < 0.001) and microalbuminuria (adjusted
      OR, 1.86; P < 0.001). Baseline pentosidine excretion predicted macroalbuminuria
      (adjusted OR, 6.89; P = 0.002). Baseline AGE fluorescence predicted
      microalbuminuria (adjusted OR, 1.68; P = 0.02). However, adjusted for NAG
      excretion, pentosidine excretion and AGE fluorescence lost the predictive
      association with macroalbuminuria and microalbuminuria, respectively.
      LIMITATIONS: Use of angiotensin-converting enzyme inhibitors was not directly
      ascertained, although their use was proscribed during the DCCT. CONCLUSIONS:
      Early in type 1 diabetes, repeated measurements of AER and urinary NAG excretion
      may identify individuals susceptible to future diabetic nephropathy. Combining
      the 2 markers may yield a better predictive model than either one alone. Renal
      tubule stress may be more severe, reflecting abnormal renal tubule processing of
      AGE-modified proteins, in individuals susceptible to diabetic nephropathy.

PMID- 20138414
TI  - Comparison of the prevalence and mortality risk of CKD in Australia using the CKD
      Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease
      (MDRD) Study GFR estimating equations: the AusDiab (Australian Diabetes, Obesity
      and Lifestyle) Study.
AB  - BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is
      more accurate than the Modification of Diet in Renal Disease (MDRD) Study
      equation. We applied both equations in a cohort representative of the Australian
      adult population. STUDY DESIGN: Population-based cohort study. SETTING &
      PARTICIPANTS: 11,247 randomly selected noninstitutionalized Australians aged >or=
      25 years who attended a physical examination during the baseline AusDiab
      (Australian Diabetes, Obesity and Lifestyle) Study survey. PREDICTORS & OUTCOMES:
      Glomerular filtration rate (GFR) was estimated using the MDRD Study and CKD-EPI
      equations. Kidney damage was defined as urine albumin-creatinine ratio >or= 2.5
      mg/mmol in men and >or= 3.5 mg/mmol in women or urine protein-creatinine ratio
      >or= 0.20 mg/mg. Chronic kidney disease (CKD) was defined as estimated GFR (eGFR)
      >or= 60 mL/min/1.73 m(2) or kidney damage. Participants were classified into 3
      mutually exclusive subgroups: CKD according to both equations; CKD according to
      the MDRD Study equation, but no CKD according to the CKD-EPI equation; and no CKD
      according to both equations. All-cause mortality was examined in subgroups with
      and without CKD. MEASUREMENTS: Serum creatinine and urinary albumin, protein, and
      creatinine measured on a random spot morning urine sample. RESULTS: 266
      participants identified as having CKD according to the MDRD Study equation were
      reclassified to no CKD according to the CKD-EPI equation (estimated prevalence,
      1.9%; 95% CI, 1.4-2.6). All had an eGFR >or= 45 mL/min/1.73 m(2) using the MDRD
      Study equation. Reclassified individuals were predominantly women with a
      favorable cardiovascular risk profile. The proportion of reclassified individuals
      with a Framingham-predicted 10-year cardiovascular risk >or= 30% was 7.2%
      compared with 7.9% of the group with no CKD according to both equations and 45.3%
      of individuals retained in stage 3a using both equations. There was no evidence
      of increased all-cause mortality in the reclassified group (age- and sex-adjusted
      hazard ratio vs no CKD, 1.01; 95% CI, 0.62-1.97). Using the MDRD Study equation,
      the prevalence of CKD in the Australian population aged >or= 25 years was 13.4%
      (95% CI, 11.1-16.1). Using the CKD-EPI equation, the prevalence was 11.5% (95%
      CI, 9.42-14.1). LIMITATIONS: Single measurements of serum creatinine and urinary
      markers. CONCLUSIONS: The lower estimated prevalence of CKD using the CKD-EPI
      equation is caused by reclassification of low-risk individuals.

PMID- 20138415
TI  - Potential new therapeutic agents for diabetic kidney disease.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease, and both
      the incidence and prevalence of diabetic nephropathy continue to increase.
      Currently, various treatment regimens and combinations of therapies provide only
      partial renoprotection. It is obvious that new approaches are desperately needed
      to retard the progression of diabetic nephropathy. Recently, a number of new
      agents have been described that have the potential to delay the progression of
      diabetic kidney disease and minimize the growing burden of end-stage renal
      disease. These include inhibitors and breakers of advanced glycation end
      products, receptor antagonists for advanced glycation end products, protein
      kinase C inhibitors, NADPH (reduced nicotinamide adenine dinucleotide phosphate)
      oxidase inhibitors, glycosaminoglycans, endothelin receptor antagonists,
      antifibrotic agents, and growth factor inhibitors. This review addresses these
      promising new therapeutic agents for delaying the progression of diabetic kidney
      disease.

PMID- 20138416
TI  - Light microscopic features of membranous nephropathy with unusual changes of the
      podocytes and glomerular basement membrane in a patient with sudden onset of
      nephrotic syndrome.

PMID- 20138417
TI  - The association between heart disease mortality and geographic access to
      hospitals: county level comparisons in Ohio, USA.
AB  - Greater distance to health care facilities is associated with poorer health care
      service utilization, yet little is known about how the 'decay effect' of distance
      influences the outcome of heart disease that requires frequent medical care.
      Heart disease has been a leading cause of death in the United States for a last
      few decades, even with significant improvements in treatment and management. In
      this study, we examined the association between physical distance to hospitals
      and heart disease mortality. The geographic information system (GIS) approach was
      taken to integrate, visualize and analyze data from multiple sources. Hospitals
      in the state of Ohio were geocoded and zonal statistics were computed to quantify
      geographical access to hospitals at the level of Ohio's 88 counties. Whereas the
      results of bivariate analysis showed a significant association between distance
      to hospitals and heart disease mortality, this relationship was not significant
      when accounting for socioeconomic and socio-demographic factors. This study
      demonstrates the usefulness of visualized health data and makes a case for
      further research on associations between disease outcomes and access to health
      care services.

PMID- 20138418
TI  - Perceived and objective neighborhood environment attributes and health related
      quality of life among the elderly in Bogota, Colombia.
AB  - This study examines associations between neighborhood environment attributes and
      health related quality of life (HRQOL) and self-rated health (SRH) among older
      adults (60 years and over) in Bogota, Colombia. Perceived and objective
      neighborhood environmental characteristics were assessed in a cross sectional
      multilevel design with 1966 older adults within 50 neighborhoods. Outcome
      variables included HRQOL (physical and mental dimensions) and SRH measured with
      the Spanish version of the Short Form 8 (SF-8). Independent variables included
      perceived and objective neighborhood characteristics as well as self-reported
      levels of walking. Hierarchical linear and logistic regression models were used
      for the analysis. Among perceived neighborhood characteristics, safety from
      traffic was positively associated with both HRQOL dimensions and SRH. Having safe
      parks was positively associated with the mental dimension of HRQOL and with SRH.
      Street noise was negatively associated with both HRQOL dimensions. Regarding
      objective neighborhood characteristics, residing in areas with more than eight
      percent of land covered by public parks was positively associated with SRH.
      Objective and perceived neighborhood characteristics could provide insight into
      potential interventions among older adults from rapidly urbanizing settings in
      Latin America.

PMID- 20138419
TI  - Use of panoramic x-ray to determine position of impacted maxillary canines.
AB  - PURPOSE: To evaluate the position of impacted maxillary canines in the alveolus
      using panoramic radiographs. MATERIALS AND METHODS: The present study was a
      retrospective chart review of 102 patients with 130 impacted maxillary canines
      from the University of Illinois at Chicago College of Dentistry and private
      practice. Of the 130 impacted maxillary canines, 59 were impacted buccally and 71
      were impacted palatally. The inclination of the impacted maxillary canines to a
      horizontal line from the mesiobuccal cusps of the maxillary molars was measured.
      We used these measurements to predict the position of the tooth and correlate
      this prediction with the actual approach used during surgery. RESULTS: The mean
      angulation of the buccally impacted maxillary canines was 75.1 degrees +/- 18.2
      degrees (range, 8 degrees to 111 degrees ). The mean angulation of the palatally
      impacted maxillary canines was 51.3 degrees +/- 15.3 degrees (range, 12 degrees
      to 91 degrees ). The mean difference between the angulation of the impacted
      maxillary canines as measured on the panoramic radiographs was statistically
      significant (P < .001). From a receiver-operator characteristic curve and using a
      logistic regression model, impactions greater than 65 degrees were 26.6 times
      more likely to be buccally impacted maxillary canines (P < .001). CONCLUSIONS:
      Panoramic radiographs are useful for predicting the location of impacted
      maxillary canines and the subsequent surgical approach required for exposure and
      orthodontic appliance attachment when computed tomography is unavailable or
      unnecessary otherwise. The use of panoramic radiographs for determing impacted
      maxillary canine position has a high sensitivity and specificity, with
      angulations greater than 65 degrees associated with buccal impactions.

PMID- 20138420
TI  - Bisphosphonate-related osteonecrosis of the jaw: is pH the missing part in the
      pathogenesis puzzle?
AB  - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of
      bisphosphonate therapy, primarily diagnosed in patients with cancer and
      metastatic bone disease and receiving intravenous administrations of nitrogen
      containing bisphosphonates. If diagnosis or treatment is delayed, BRONJ can
      develop to a severe and devastating disease. Numerous studies have focused on
      BRONJ, with possible pathomechanisms identified to be oversuppression of bone
      turnover, ischemia due to antiangiogenetic effects, local infections, or soft
      tissue toxicity. However, the precise pathogenesis largely remains elusive and
      questions of paramount importance await to be answered, namely 1) Why is only the
      jaw bone affected? 2) Why and how do the derivatives differ in their potency to
      induce a BRONJ? and 3) Why and when is BRONJ manifested? The present perspective
      reflects on existing theories and introduces the hypothesis that local tissue
      acidosis in the jaw bone offers a conclusive pathogenesis model and may prove to
      be the missing link in BRONJ.

PMID- 20138421
TI  - Prevalence and factors linked to atopic eczema in 10- and 11-year-old
      schoolchildren. Isaac 2 in Almeria, Spain.
AB  - BACKGROUND: Atopic eczema affects 5-10% of the Spanish paediatric population, and
      has increased in frequency over the last few decades, probably due to changes in
      the environment and lifestyle. Phase II of the ISAAC (International Study of
      Asthma and Allergies in Childhood) uses a standardised methodology to establish
      the prevalence of allergic disorders and factors linked to them in each centre.
      OBJECTIVES: To assess the prevalence and severity of atopic eczema, and to
      establish factors linked to atopic eczema in 10-11 year-old school children in
      the city of Almeria (South-East coast of Spain). MATERIAL AND METHODS: An
      ecological study was carried out as part of ISAAC II, using homologated
      questionnaires and allergic tests in 1143 schoolchildren. Statistic association
      was assessed by means of chi(2) test, and then logistic regression analysis was
      performed with the most significant variables from the univariant analysis.
      RESULTS: The prevalence of atopic eczema was 11.4%. The risk factors found in the
      multiple logistic regression analysis were: personal antecedents of severe asthma
      (OR 19 CI 95% 1.35-266) and severe rhinitis (OR 7.7 CI 95% 1.79-33), fungi in
      bedroom during the first year of life (OR 4.2 CI 95% 1.17-15.1) and atopic eczema
      in one parent (OR 5.2 CI 95% 2.69-10.1). CONCLUSIONS: The prevalence of atopic
      eczema is similar to that found in other studies within ISAAC Phase I. The most
      important risk factors for atopic eczema are family and personal history of other
      atopic diseases and the presence of fungi in the home.

PMID- 20138422
TI  - Differentiation potential of germ line stem cells derived from the postnatal
      mouse ovary.
AB  - General belief in reproductive biology is that in most mammals female germ line
      stem cells are differentiated to primary oocytes during fetal development and
      oogenesis starts from a pool of primordial follicles after birth. This idea has
      been challenged previously by using follicle kinetics studies and demonstration
      of mitotically active germ cells in the postnatal mouse ovary (Johnson et al.,
      2004; Kerr et al., 2006; Zhang et al., 2008). However, the existence of a
      population of self-renewing ovarian germ line stem cells in postnatal mammals is
      still controversial (Eggan et al., 2006; Telfer et al., 2005; Gosden, 2004).
      Recently, production of offspring from a germ line stem cell line derived from
      the neonatal mouse ovary was reported (Zou et al., 2009). This report strongly
      supports the existence of germ line stem cells and their ability to expand in
      vitro. Recently, using a transgenic mouse model in which GFP is expressed under a
      germ cell-specific Oct-4 promoter, we isolated and generated multipotent cell
      lines from male germ line stem cells (Izadyar et al., 2008). Using the same
      strategy we isolated and derived cell lines from postnatal mouse ovary.
      Interestingly, ovarian germ line stem cells expanded in the same culture
      conditions as the male suggesting that they have similar requirements for their
      self-renewal. After 1 year of culture and many passages, ovarian germ line stem
      cells maintained their characteristics and telomerase activity, expressed germ
      cell and stem cell markers and revealed normal karyotype. As standard protocol
      for differentiation induction, these cells were aggregated and their ability to
      form embryoid bodies (EBs) was investigated. EBs generated in the presence of
      growth factors showed classical morphology and expressed specific markers for
      three germ layers. However, in the absence of growth promoting factors EBs were
      smaller and large cells with the morphological and molecular characteristics of
      oocytes were formed. This study shows the existence of a population of germ line
      stem cell in postnatal mouse ovary with multipotent characteristics.

PMID- 20138423
TI  - Low quality of evidence for robot-assisted laparoscopic prostatectomy: results of
      a systematic review of the published literature.
AB  - BACKGROUND: Robot-assisted laparoscopic prostatectomy (RALP) is displacing
      radical retropubic prostatectomy as the gold standard surgical approach for
      clinically localised prostate cancer in the United States and is also being
      increasingly used in Europe and other parts of the world. This trend has occurred
      despite the paucity of high-quality evidence to support its relative superiority
      to more established treatment modalities. OBJECTIVE: We performed this study to
      critically assess the quality of published evidence on RALP to support this major
      shift in practice patterns. DESIGN, SETTING, AND PARTICIPANTS: We conducted a
      systematic review of the published literature through Medline and Embase (1966 to
      December 2008). All original research publications on RALP were included.
      Editorials, letters to the editor, and review articles were excluded.
      MEASUREMENTS: Two reviewers independently performed the data abstraction using a
      standardised form derived from the Strengthening the Reporting of Observational
      Studies in Epidemiology (STROBE) criteria. RESULTS AND LIMITATIONS: Seventy-five
      original research publications met eligibility criteria. Fifty-five (73.3%)
      studies were published between 2005 and 2008, and 20 studies (26.7%) were
      published between 2001 and 2004. Approximately three-quarters of the studies were
      case series (74.7%), and only two (2.7%) randomised, controlled trials (RCT) were
      identified. Twelve authors cowrote 72% (54 of 75) of the published studies.
      Reporting of STROBE criteria ranged from 100.0% (scientific rationale/background
      explained) to 1.3% (consideration of sample size), with no improvement over time.
      The study was limited to published literature in the English language.
      CONCLUSIONS: The published RALP literature is limited to observational studies of
      mostly low methodologic quality. Our findings draw into question to what extent
      valid conclusions about the relative superiority or equivalence of RALP to other
      surgical approaches can be drawn and whether published outcomes can be
      generalised to the broader community. There is an urgent need to raise the
      methodologic standards for clinical research on new urologic procedures and
      devices.

PMID- 20138424
TI  - Phosphorylated c-Jun NH2-terminal kinase is overexpressed in human papillary
      thyroid carcinomas and associates with lymph node metastasis.
AB  - To evaluate the associations of phosphorylated c-Jun NH2-terminal kinase (p-JNK)
      expression with clinicopathological features in patients with papillary thyroid
      carcinoma, p-JNK expression were immunohistochemically measured in 121 thyroid
      samples. p-JNK was overexpressed in papillary thyroid carcinomas with respect to
      matched nontumorous tissues (P=0.000), which was supported by western blot
      analysis. Increased p-JNK expression was significantly associated with the
      presence of lymph node metastases (P=0.001) and advanced TNM stages (P=0.02).
      Furthermore, p-JNK expression was positively correlated with osteopontin (OPN)
      expression (r=0.58, P<0.001). Activation of p-JNK may play a role in the
      carcinogenesis and lymph node metastasis of papillary thyroid carcinoma, and may
      be a molecular target for therapeutic intervention.

PMID- 20138425
TI  - Review: In situ and bioremediation of organic pollutants in aquatic sediments.
AB  - Organic pollutants in sediments are a worldwide problem because sediments act as
      sinks for hydrophobic, recalcitrant and hazardous compounds. Depending on
      biogeochemical processes these hydrocarbons are involved in adsorption,
      desorption and transformation processes and can be made available to benthic
      organisms as well as organisms in the water column through the sediment-water
      interface. Most of these recalcitrant hydrocarbons are toxic and carcinogenic,
      they may enter the food-chain and accumulate in biological tissue. Several
      approaches are being investigated or have been already used to remove organic
      hydrocarbons from sediments. This paper provides a review on types and sources of
      organic pollutants as well as their behavior in sediments. It presents the
      advantages and disadvantages of traditional sediment remediation techniques in
      use, such as dredging, capping and monitored natural attenuation. Furthermore, it
      describes new approaches with emphasis on bioremediation, like biostimulation,
      bioaugmentation and phytoremediation applied to sediments. These new techniques
      promise to be of lower impact and more cost efficient than traditional management
      strategies.

PMID- 20138426
TI  - High photocatalytic degradation activity of the polyvinyl chloride (PVC)-vitamin
      C (VC)-TiO2 nano-composite film.
AB  - A novel photodegradable polyvinyl chloride (PVC)-vitamin C (VC)-TiO(2) nano
      composite film was prepared by embedding VC modified nano-TiO(2) photocatalyst
      into the commercial PVC plastic. The solid-phase photocatalytic degradation
      behavior of PVC-VC-TiO(2) nano-composite film under UV light irradiation was
      investigated and compared with those of the PVC-TiO(2) film and the pure PVC
      film, with the aid of UV-Vis spectroscopy, scanning electron microscopy (SEM),
      weight loss monitoring, and X-ray diffraction spectra (XRD). The results show
      that PVC-VC-TiO(2) nano-composite film has a high photocatalytic activity; the
      photocatalytic degradation rate of it is two times higher than that of PVC-TiO(2)
      film and fifteen times higher than that of pure PVC film. The optimal mass ratio
      of VC to TiO(2) is found to be 0.5. The mechanism of enhancing photocatalytic
      activity is attributed to the formation of a Ti(IV)-VC charge-transfer complex
      with five-member chelate ring structure and a rapid photogenerated charge
      separation is thus achieved.

PMID- 20138427
TI  - Effect of inoculum/substrate ratio on methane yield and orthophosphate release
      from anaerobic digestion of Microcystis spp.
AB  - A batch anaerobic test was conducted to evaluate the effects of
      inoculum/substrate ratios (ISRs) on the methane yield and orthophosphate release
      from the anaerobic digestion of Microcystis spp. The results demonstrated an
      obvious influence on methane yield and orthophosphate release by ISR. The maximum
      methane yield decreased from 140.48 to 94.42 mL/gVS when the ISR decreased from
      2.0 to 0.5. The highest maximum methane yield calculated from Orskov equation was
      153.66 mL/gVS at ISR value of 1.0. The values of pH, ammonia and volatile fatty
      acids (VFAs) corroborated the appropriate stability of this anaerobic process.

PMID- 20138428
TI  - Co-existence of anammox and denitrification for simultaneous nitrogen and carbon
      removal--Strategies and issues.
AB  - The discovery of anaerobic ammonium oxidation (anammox) has greatly improved the
      understanding of the nitrogen cycle. Anammox provides great promise for the
      removal of nitrogen from wastewater, containing high concentration of ammonium.
      However, the presence of organic carbon is considered as unfavorable to this
      autotrophic process, i.e. anammox. Most of the real wastewaters contain both
      organic carbon and nitrogen. Under this circumstance, several processes have been
      established primarily for the complete removal of organic carbon. Subsequently,
      the wastewater containing no or low organic carbon and nitrogen is treated via a
      variety of nitrogen removal processes. The co-existence of anammox and
      denitrification could be useful for the simultaneous removal of nitrogen and
      organic carbon in a single system rather than a sequential chain of treatment.
      This review addresses the microbiology, strategies, consequences and the future
      research challenges in the co-existence of anammox and denitrification.

PMID- 20138429
TI  - The human vasodilator axon reflex - an exclusively peripheral phenomenon?
AB  - The effect of regional anesthesia of the brachial plexus on the size and
      intensity of the histamine-induced axon reflex flare (neurogenic inflammation) of
      the forearm and the upper arm was compared to that of the contralateral arm as
      control in humans. No changes in the axon reflex could be assessed. Thus the
      lateral spread of the axon reflex flare must be transmitted by peripheral nerve
      branches not affected by the anesthesia in the axilla. This excludes the
      existence of physiologically relevant amounts of proximal branchpoints, DRG
      neurons with multiple peripheral axons or spinal interneurons transmitting action
      potentials between peripheral C-afferents involved in the axon reflex flare.
      Mechanoinsensitive C-fibres are known to be activated by histamine and to be
      responsible for the neuropeptide release in the skin inducing the axon reflex
      flare. Reports on those proximal connections can therefore obviously not extend
      to mechanoinsensitive C-fibres and do not explain the origin of neurogenic
      inflammation in humans without prior sensitization.

PMID- 20138430
TI  - Reference values for quantitative sensory testing in children and adolescents:
      developmental and gender differences of somatosensory perception.
AB  - The Quantitative Sensory Testing (QST) protocol of the German research network on
      neuropathic pain (DFNS) encompassing all somatosensory modalities assesses the
      functioning of different nerve fibers and of central pathways. The aim of our
      study was: (1) to explore, whether this QST protocol is feasible for children,
      (2) to detect distribution properties of QST data and the impact of body site,
      age and gender and (3) to establish reference values for QST in children and
      adolescents. The QST protocol of the DFNS with modification of instructions and
      pain rating was used in 176 children aged 6.12-16.12years for six body sites. QST
      was feasible for children over 5years of age. ANOVAs revealed developmental,
      gender and body site differences of somatosensory functions similar to adults.
      The face was more sensitive than the hand and/or foot. Younger children (6
      8years) were generally less sensitive to all thermal and mechanical detection
      stimuli but more sensitive to all pain stimuli than older (9-12years) children,
      whereas there were little differences between older children and adolescents (13
      17years). Girls were more sensitive to thermal detection and pain stimuli, but
      not to mechanical detection and pain stimuli. Reference values differ from
      adults, but distribution properties (range, variance, and side differences) were
      similar and plausible for statistical factors. Our results demonstrate that the
      full QST protocol is feasible and valid for children over 5years of age with
      their own reference values.

PMID- 20138431
TI  - Epidemiologic aspects of an outbreak of Trypanosoma vivax in a dairy cattle herd
      in Minas Gerais state, Brazil.
AB  - The aim of this study was to assess the epidemiological situation of bovine
      trypanosomiasis caused by Trypanosoma vivax in a dairy cattle herd from Igarape,
      Minas Gerais state, Brazil. The herd was monitored from September 2007 to
      February 2009 by sampling blood for determination of packed cell volume (PCV),
      microhaematocrit centrifugation test of parasitaemia (MHCT), serology (IFA),
      morphological identification of T. vivax and molecular diagnosis by polymerase
      chain reaction (PCR). During all the experimental period, 25 animals were MHCT
      and PCR positive, considering that in each sample collection a mean of 70 animals
      was evaluated. The morphometric characteristics of trypomastigote forms confirmed
      the infection by T. vivax. The seroprevalence ranged from 7.4% in September 2007
      to 48% in February 2009, and the highest incidence observed could be correlated
      with an increased population of Stomoxys calcitrans flies in that region. Anaemia
      was the most important change found in infected animals, which showed lower
      averages of PCV than parasitologically negative animals (p<0.0001). Infected
      individuals showed lower averages of PCV than parasitologically negative animals
      (p<0.0001), indicating higher anaemia in the former compared with the latter
      group.

PMID- 20138432
TI  - Epidemiological features of fasciolosis in working donkeys in Ethiopia.
AB  - A cross-sectional coprological survey in the tropical regions of Ada, Akaki,
      Bereh and Boset, and a retrospective post-mortem investigation were conducted to
      study the epidemiology of fasciolosis in working donkeys in Ethiopia. Faecal
      samples from 803 donkeys were collected, and the number of liver flukes recovered
      from 112 donkeys at post-mortem between 1995 and 2004 were analysed. There was a
      high prevalence of fasciolosis irrespective of the age of the donkeys. The
      overall prevalence of the infection was 44.4% in coprologically examined donkeys,
      and the prevalence in the donkeys examined post-mortem was 41.9%. The infection
      prevalence was significantly higher in Bereh and Ada regions than in Akaki and
      Boset regions. Bereh with 72.6% and Boset with 21.5% showed a significantly
      higher and lower infection prevalence, respectively, than the rest of the regions
      (P<0.001). There was no significant difference between different age groups of
      donkeys in the infection prevalence (P>0.05) but infection intensity was
      significantly higher in donkeys 8 years old and above (P<0.0001). Both Fasciola
      hepatica and Fasciola gigantica were identified.

PMID- 20138433
TI  - A molecular survey of cystic echinococcosis in Sudan.
AB  - A survey of cystic echinococcosis in livestock was conducted from May 2001 to
      July 2003 in central, western and southern Sudan. Hydatid cysts were present in
      59% (466/779) of camels, 6% (299/4893) of cattle, 11% (1180/10,422) of sheep and
      2% (106/5565) of goats, with little variation among different geographical areas.
      532 of these cysts were examined by PCR and could be overwhelmingly (98.7%)
      allocated to Echinococcus canadensis G6/7 (all of 215 cysts from camels, 112 of
      114 cysts from cattle, 134 of 138 cysts from sheep, and all of 65 cysts from
      goats); the genotype G6 was identified by sequencing 13 of these isolates. Only 2
      cysts from cattle belonged to Echinococcus ortleppi. The mean number of cysts per
      infected animal was much higher in camels (5.1) than in the other species (1.0
      1.3), and cyst fertility was higher in camels and cattle (74% and 77%) than in
      goats and sheep (31% and 19%). Fertile cysts from five human patients from
      hospitals in Khartoum and Juba belonged to E. canadensis (G6). This study
      confirms the predominance of the 'camel strain' in Sudan and the infectivity of
      this strain for humans. This is the first genetic characterization of human CE in
      Sudan.

PMID- 20138434
TI  - Seroprevalence of equine piroplasms and host-related factors associated with
      infection in Greece.
AB  - Serum samples were collected from a total of 544 equids that included 524 horses,
      13 mules, and 7 ponies from various regions of mainland Greece and were examined
      by competitive-inhibition ELISA (cELISA) to evaluate the level of exposure of
      Greek equids to Theileria (Babesia) equi and/or Babesia caballi, the causative
      agents of piroplasmosis. Association between seropositivity and host-related
      factors of species, gender, age, origin, activity and location were investigated.
      The overall seroprevalence was 11.6% (9.1-14.6%) with 95% confidence limit. The
      seroprevalence for T. equi and B. caballi was found to be 11% (8.6-14%) and 2.2%
      (1.2-3.9%), respectively. The animal-related factors significantly linked with
      seropositivity were the species, activities of farming, racing, recreation, and
      geographic location in Attica, Macedonia, Peloponnese and Thessaly region
      (p<0.05). The relative risks for the presence of T. equi, B. caballi and mixed
      infection in mules compared to horses was 8.39, 33.58 and 40.31, respectively.
      The infection level for T. equi, B. caballi and mixed infection were
      significantly higher in farm equids than in racing equids (p<0.05). Also, the
      rate of infection of T. equi was higher in farm equids than recreational equids
      (p<0.05). The relative risk of T. equi infection between farming equids and
      equids used only for recreation activity was 3.25-1, while the relative risk of
      B. caballi infection was 0.14-1 for racing animals relative to recreation
      animals. The region with the highest level of infection to both parasites was
      Thessaly (38.8% T. equi and 6.1% B. caballi), followed by Peloponnese (10.4% T.
      equi and 3.9% B. caballi), Attica region (8.3% T. equi and 0.6% B. caballi) and
      finally Macedonia the region with the lowest prevalence (6.6% T. equi and 4.4% B.
      caballi). A higher seroprevalence rate was found among local animals compared to
      imported equids, indicating that equine piroplasm infection is enzootic in
      Greece. T. equi seroprevalence was significantly different and higher among
      increasing age groups of equids, suggesting persistent infections or lower
      transmission levels whereby animals may need to be exposed longer before
      acquiring the infection. Competent tick vectors Rhipicephalus bursa and
      Rhipicephalus sanguineus for the transmission of equine piroplasmosis were
      recovered from horses and dogs, respectively.

PMID- 20138435
TI  - Estradiol-induced desensitization of 5-HT1A receptor signaling in the
      paraventricular nucleus of the hypothalamus is independent of estrogen receptor
      beta.
AB  - Estradiol regulates serotonin 1A (5-HT(1A)) receptor signaling. Since
      desensitization of 5-HT(1A) receptors may be an underlying mechanism by which
      selective serotonin reuptake inhibitors (SSRIs) mediate their therapeutic effects
      and combining estradiol with SSRIs enhances the efficacy of the SSRIs, it is
      important to determine which estrogen receptors are capable of desensitizating 5
      HT(1A) receptor function. We previously demonstrated that selective activation of
      the estrogen receptor, GPR30, desensitizes 5-HT(1A) receptor signaling in rat
      hypothalamic paraventricular nucleus (PVN). However, since estrogen receptor-beta
      (ERbeta), is highly expressed in the PVN, we investigated the role of ERbeta in
      estradiol-induced desensitization of 5-HT(1A) receptor signaling. We first showed
      that a selective ERbeta agonist, diarylpropionitrile (DPN) has a 100-fold lower
      binding affinity than estradiol for GPR30. Administration of DPN did not
      desensitize 5-HT(1A) receptor signaling in rat PVN as demonstrated by agonist
      stimulated hormone release. Second, we used a recombinant adenovirus containing
      ERbeta siRNAs to decrease ERbeta expression in the PVN. Reductions in ERbeta did
      not alter the estradiol-induced desensitization of 5-HT(1A) receptor signaling in
      oxytocin cells. In contrast, in animals with reduced ERbeta, estradiol
      administration, instead of producing desensitization, augmented the ACTH response
      to a 5-HT(1A) agonist. Combined with the results from the DPN treatment
      experiments, desensitization of 5-HT(1A) receptor signaling does not appear to be
      mediated by ERbeta in oxytocin cells, but that ERbeta, together with GPR30, may
      play a complex role in central regulation of 5-HT(1A)-mediated ACTH release.
      Determining the mechanisms by which estrogens induce desensitization may aid in
      the development of better treatments for mood disorders.

PMID- 20138436
TI  - Prolonged inflammation following critical illness may impair long-term survival:
      a hypothesis with potential therapeutic implications.
AB  - Despite successful intensive care a substantial portion of critically ill
      patients dies after discharge from the intensive care unit or hospital.
      Observational studies investigating long-term survival of critically ill patients
      reported that most deaths occur during the first months or year after discharge.
      Only limited data on the causes of impaired quality of life and post-intensive
      care unit deaths exist in the current literature. In this manuscript we
      hypothesize that the acute inflammatory response which characteristically
      accompanies critical illness is ensued by a prolonged imbalance or activation of
      the immune system. Such a chronic low-grade inflammatory response to critical
      illness may be sub-clinical and persist for a variable period of time after
      discharge from the intensive care unit and hospital. Chronic inflammation is a
      well-recognized risk factor for long-term morbidity and mortality, particularly
      from cardiovascular causes, and may thus partly contribute to the impaired
      quality of life as well as increased morbidity and mortality following intensive
      care unit and hospital discharge of critically ill patients. Assuming that
      critical illness is indeed followed by a prolonged inflammatory response,
      important implications for treatment would arise. An interesting and potentially
      beneficial therapy could be the administration of immune-modulating drugs during
      the time after intensive care unit or hospital discharge until chronic
      inflammation has subsided. Statins are well-investigated and effective drugs to
      attenuate chronic inflammation and could potentially also improve long-term
      outcome of critically ill patients after intensive care unit or hospital
      discharge. Future studies evaluating the course of inflammation during and after
      critical illness as well as its response to statin therapy are required.

PMID- 20138437
TI  - Unexpected, periodic and permanent increase in medical inpatient care: man-made
      or new disease?
AB  - For many years medical admissions to acute hospitals have been increasing at a
      rate far higher than expected from demographic change. Factors such as emergency
      re-admission, GP thresholds, breakdown of the family unit and deficiencies in
      community and social care have been suggested to explain this widening gap.
      Solutions to the problem have revolved around demand management strategies. While
      such strategies do result in a relative reduction in demand they are unable to
      prevent the underlying long-term behaviour. Analysis of daily admissions in
      Scotland, England and at individual hospitals over the past 25 years shows that
      the admissions tend to increase in a step-like manner at an interval of three to
      six years. This causes a typical 10% step-increase in physician work-load and
      inpatient medical costs and across England adds over 1,200,000 occupied bed days
      of additional bed demand into the health service within the space of around three
      months. There are knock-on effects to demand for ambulance services, accident and
      emergency attendance and GP referral. The step-increase is characterised by a
      cluster of diagnoses, increases with age and effects women more than men. Such
      behaviour has similarities to an infectious outbreak and the evidence for this
      and alternative hypotheses are discussed.

PMID- 20138438
TI  - Human semen: the biological basis of sexual behaviour to promote human
      papillomavirus infection and cervical cancer.
AB  - Human papillomavirus (HPV) infection is the second leading cause of cancer
      associated morbidity and mortality among sexually active women worldwide due to
      its prerequisite role in cervical carcinogenesis. However, HPV infection alone is
      not sufficient to bring about cervical cancer. Sexual behaviour is consistently
      the most important co-factor for HPV infection and cervical cancer, but what is
      the underlying biological basis? In this paper, we postulate that human semen is
      the biological basis of sexual behaviour to promote HPV infection and cervical
      cancer. Based on international collaboration of epidemiological investigations
      and various HPV-infected in vivo models, it is likely for us to explore the exact
      role and pathogenesis of human semen in HPV infection and cervical
      carcinogenesis. If our hypothesis is true, regular use of condoms in the sexual
      intercourse should be recommended as a way of preventing genital transmission of
      HPV and reducing the incidence of cervical cancer, no matter women are infected
      by HPV or not.

PMID- 20138439
TI  - Sticking the pieces together: a unifying hypothesis for the acupuncture meridian
      pathways and extracellular signalling.

PMID- 20138440
TI  - Common chromosomal fragile sites (CFS) may be involved in normal and traumatic
      cognitive stress memory consolidation and altered nervous system immunity.
AB  - Previous reports of specific patterns of increased fragility at common
      chromosomal fragile sites (CFS) found in association with certain
      neurobehavioural disorders did not attract attention at the time due to a shift
      towards molecular approaches to delineate neuropsychiatric disorder candidate
      genes. Links with miRNA, altered methylation and the origin of copy number
      variation indicate that CFS region characteristics may be part of chromatinomic
      mechanisms that are increasingly linked with neuroplasticity and memory. Current
      reports of large-scale double-stranded DNA breaks in differentiating neurons and
      evidence of ongoing DNA demethylation of specific gene promoters in adult
      hippocampus may shed new light on the dynamic epigenetic changes that are
      increasingly appreciated as contributing to long-term memory consolidation. The
      expression of immune recombination activating genes in key stress-induced memory
      regions suggests the adoption by the brain of this ancient pattern recognition
      and memory system to establish a structural basis for long-term memory through
      controlled chromosomal breakage at highly specific genomic regions. It is
      furthermore considered that these mechanisms for management of epigenetic
      information related to stress memory could be linked, in some instances, with the
      transfer of the somatically acquired information to the germline. Here,
      rearranged sequences can be subjected to further selection and possible eventual
      retrotranscription to become part of the more stable coding machinery if proven
      to be crucial for survival and reproduction. While linkage of cognitive memory
      with stress and fear circuitry and memory establishment through structural DNA
      modification is proposed as a normal process, inappropriate activation of immune
      like genomic rearrangement processes through traumatic stress memory may have the
      potential to lead to undesirable activation of neuro-inflammatory processes.
      These theories could have a significant impact on the interpretation of risks
      posed by heredity and the environment and the search for neuropsychiatric
      candidate genes.

PMID- 20138441
TI  - Concordance between HER-2 and steroid hormone receptor expression between primary
      breast cancer, sentinel node metastases, and isolated tumor cells.
AB  - Our aim was to compare the HER-2 and hormone receptor status between primary
      tumor (PT) and sentinel node (SN) metastases in breast cancer. We analyzed 65 PTs
      with 42 macrometastases, 18 micrometastases, and 5 ITCs for the HER-2
      amplification status and for the hormone receptor status. In HER-2-positive PTs,
      26 of 29 metastases were HER-2-positive, including all six analyzed
      micrometastases and ITCs. Three macrometastases were HER-2-negative. In HER-2
      negative PTs, 35 of 36 metastases were HER-2-negative. A low-grade HER-2
      amplification was detected in one micrometastasis. A full concordance between the
      PT and SN metastases in both HER-2 amplification and ER and PR status was
      observed in 40 of 56 (71%) cases. These 40 fully concordant cases included 27
      macrometastatic, 9 micrometastatic, and 4 ITC-cases. The concordance in HER-2,
      ER, and PR was high between the PT and their SN metastases. However, the
      concordance may be remarkably lower when analyzed simultaneously for all three
      predictive factors.

PMID- 20138442
TI  - Long-term outcome and toxicity of salvage brachytherapy for local failure after
      initial radiotherapy for prostate cancer.
AB  - PURPOSE: To describe long-term outcomes and toxicity after salvage brachytherapy
      (BT) for local failure after initial radiotherapy for prostate cancer. METHODS
      AND MATERIALS: Between 1994 and 2008, 37 men with local failure after initial
      prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT)
      underwent salvage BT with (103)Pd or (125)I. Estimates of freedom from
      biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS)
      were calculated using the Kaplan-Meier method. Toxicities were graded using
      CTCv3.0. RESULTS: Median follow-up was 86 months (range, 2-156). The median dose
      to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and
      CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific
      antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with
      FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA
      <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only
      presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved
      FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph
      node dissection before salvage BT was the only variable significantly associated
      with Grade > or = 2 toxicity (p = 0.03). CONCLUSION: With a median follow-up of
      86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS
      of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was
      worse in patients who had undergone pelvic lymph node dissection before salvage
      BT. Careful patient selection for salvage BT may result in improved outcomes and
      reduced toxicity.

PMID- 20138443
TI  - Concurrent liposomal cisplatin (Lipoplatin), 5-fluorouracil and radiotherapy for
      the treatment of locally advanced gastric cancer: a phase I/II study.
AB  - PURPOSE: Liposomal drugs have a better tolerance profile and are highly
      accumulated in the tumor environment, properties that promise an optimal
      radiosensitization. We investigated the feasibility of the combination of 5
      fluorouracil/lecovorin-based radio-chemotherapy with the administration of high
      weekly dose of a liposomal platinum formulation (Lipoplatin). METHODS AND
      MATERIALS: Lipoplatin was given at a dose of 120 mg/m(2)/week, 5-fluorouracil at
      400mg/m(2)/week (Day 1), whereas radiotherapy was given through 3.5-Gy fractions
      on Days 2, 3, and 4. Two groups of 6 patients received four and five consecutive
      cycles, respectively. RESULTS: Minimal nephrotoxicity (18.2% Grade 1) and
      neutropenia (9% Grade 3) was noted. Fatigue Grade 2 appeared in 25% of cases.
      Abdominal discomfort was reported by 18% of patients. No liver, kidney, gastric,
      or intestinal severe acute or late sequellae were documented, although the median
      follow-up of 9 months is certainly too low to allow safe conclusions. A net
      improvement in the performance status (from a median of 1 to 0) was recorded 2
      months after the end of therapy. The response rates assessed with computed
      tomography, endoscopy, and biopsies confirmed 33% (2 of 6) tumor disappearance in
      patients treated with four cycles, which reached 80% (4 of 5) in patients
      receiving five cycles. CONCLUSIONS: Lipoplatin radio-chemotherapy is feasible,
      with minor hematological and nonhematological toxicity. The high complete
      response rates obtained support the testing of Lipoplatin in the adjuvant
      postoperative or preoperative radio-chemotherapy setting for the treatment of
      gastric cancer.

PMID- 20138444
TI  - Clinical study of the necessity of replanning before the 25th fraction during the
      course of intensity-modulated radiotherapy for patients with nasopharyngeal
      carcinoma.
AB  - PURPOSE: To quantify the target and normal structures on dose distributing
      variations during intensity-modulated radiotherapy (IMRT) and to assess the value
      of replanning for nasopharyngeal carcinoma (NPC) patients. METHODS AND MATERIALS:
      Twenty-eight NPC patients treated with IMRT were recruited. The IMRT was
      delivered in 33 fractions, to 70 to 76Gy, to the gross tumor volume (GTV). Before
      the 25th fraction of IMRT, a new simulation computed tomography (CT) scan was
      acquired for all patients. According to the dose constraint criterion in the
      Radiation Therapy Oncology Group (RTOG) 0225 protocol, the replanning was
      generated on the new simulation CT. With the Quality Assessment Center of a
      CORVUS 6.3 treatment planning system, a phantom plan was generated for each
      patient by applying the beam configurations of the initial plan to the anatomy of
      the new simulation CT. The dose-volume histograms of the phantom plan were
      compared with the replanning. RESULTS: The percentage of prescription dose
      delivered to the clinical target volume (CTV1) was significantly increased by
      4.91% +/- 10.89%, whereas the maximum dose to the spinal cord, mean dose to the
      left parotid, and V30 to the right parotid were significantly decreased by 5.00
      +/- 9.23Gy, 4.23 +/- 10.03Gy, and 11.47% +/- 18.89% respectively in the
      replanning, compared with the phantom plan (p < 0.05). Based on the dose
      constraint criterion in the RTOG0225 protocol, 50% of phantom plans (14/28) were
      out of limit for the dose to the normal critical structures, whereas no plan was
      out of limit in replanning (p < 0.001). CONCLUSION: Replanning for patients with
      NPC before the 25th fraction during IMRT helps to ensure adequate dose to the
      target volumes and safe doses to critical normal structures.

PMID- 20138445
TI  - Biomechanical comparison of contemporary clavicle fixation devices.
AB  - PURPOSE: Because recent studies have shown that malunited or nonunited clavicle
      fractures treated nonsurgically have poor outcomes, early fixation of certain
      clavicle shaft fractures using contemporary implants has become more common.
      Little is known about the physiologic loading of these implants. This study was
      designed to observe the biomechanical behavior and strength of implants used for
      fixation of the clavicle shaft. METHODS: We used synthetic clavicle bones that
      were produced in 2 pieces to replicate the conditions of a transverse fracture.
      Ten specimens per group were tested using 3 clavicle fixation constructs:
      precontoured clavicle plates with unicortical locking, precontoured clavicle
      plates with bicortical nonlocking screws, and intramedullary Rockwood clavicle
      pins. Two loading conditions were used: cantilever bending and 3-point bending.
      RESULTS: For cantilever bending, both plate groups failed by fracture at the most
      medial screw hole. The pin group was unable to resist the small torque associated
      with off-axis loading. The pin group failed at a lower maximum load, which
      occurred with a greater maximum displacement. The pin group was also less stiff
      than the plate group. In the 3-point bending test, the pin group was
      significantly more flexible and achieved higher failure loads than the plate
      groups. There were no significant differences between the unicortical and
      bicortical screws for any of the measured variables with either loading
      condition. CONCLUSIONS: Both locking and nonlocking constructs appear to provide
      similar rigid fixation under the tested mechanical conditions. The intramedullary
      pin can provide high resistance to failure loads in situations when rigidity and
      rotational stiffness are not required. Intramedullary pin fixation appears to be
      inadequate where rotational stiffness is required.

PMID- 20138446
TI  - Iron retention in preterm infants fed low iron intakes: a metabolic balance
      study.
AB  - There is little data on iron retention in healthy preterm infants. Twenty-four
      metabolic balance studies were carried out in 13 preterm infants between 17 and
      63 days of age, in 11 cases 2 balance were carried out 7d apart. Iron intake was
      1.11 mg/kg/day (SD 0.06), less than the 2 mg/kg/d typically recommended for
      preterm infants. Iron retention was positive in the majority (3/13) of the first
      balances, and in all 11 of the second balances. Iron retention increased
      significantly between the two balances (from 0.095 mg/kg/d (SD 0.178) to 0.270
      (SD 0.209)). Iron retention was significantly related to the time that the infant
      had been on enteral feeds at the time the balance was carried out. Iron retention
      was significantly greater than the requirement estimated to be needed to meet the
      needs for growth and expansion of the circulating red cell mass. Iron intakes of
      about 1mg/kg/d seem to be adequate to support the requirements for growth in
      preterm infants during this time period, but are significantly less than the
      estimated in utero accretion rate of the fetus.

PMID- 20138447
TI  - [Gastrointestinal stromal tumors (GIST)<5 cm in size: review of the literature
      and expert propositions for clinical management].
AB  - Clinical recommendations for diagnosis, treatment and follow-up of GIST have been
      established. However, management of tumors limited in size, more often diagnosed
      by gastroenterologists, remains controversial. The aim of this work was in a
      first part to analyze the literature on GIST less than 5cm in size and in a
      second part to elaborate propositions for the clinical management based on an
      expert panel opinion.

PMID- 20138448
TI  - Development of diffuse psoriasis with alopecia during treatment of Crohn's
      disease with infliximab.

PMID- 20138449
TI  - Comparative study of the sensitivity of ADC value and T2 relaxation time for
      early detection of Wallerian degeneration.
AB  - BACKGROUND AND PURPOSE: Wallerian degeneration (WD), the secondary degeneration
      of axons from cortical and subcortical injuries, is associated with poor
      neurological outcome. There is some quantitative MR imaging techniques used to
      estimate the biologic changes secondary to delayed neuronal and axonal losses.
      Our purpose is to assess the sensitivity of ADC value and T(2) relaxation time
      for early detection of WD. METHODS: Ten male Sprague-Dawley rats were used to
      establish in vivo Wallerian degeneration model of CNS by ipsilateral motor
      sensory cortex ablation. 5 days after cortex ablation, multiecho-T(2) relaxometry
      and multi-b value DWI were acquired by using a 7T MR imaging scanner. ADC-map and
      T(2)-map were reconstructed by post-processing. ROIs are selected according to
      pathway of corticospinal tract from cortex, internal capsule, cerebral peduncle,
      pons, medulla oblongata to upper cervical spinal cord to measure ADC value and
      T(2) relaxation time of healthy side and affected side. The results were compared
      between the side with cortical ablation and the side without ablation. RESULTS:
      Excluding ablated cortex, ADC values of the corticospinal tract were
      significantly increased (P<0.05) in affected side compared to the unaffected,
      healthy side; no difference in T(2) relaxation time was observed between the
      affected and healthy sides. Imaging findings were correlated with histological
      examinations. CONCLUSION: As shown in this animal experiment, ADC values could
      non-invasively demonstrate the secondary degeneration involving descending white
      matter tracts. ADC values are more sensitive indicators for detection of early WD
      than T(2) relaxation time.

PMID- 20138450
TI  - Effects of respiratory manoeuvres on hepatic vein Doppler waveform and flow
      velocities in a healthy population.
AB  - OBJECTIVE: This study was performed to determine the variations in Doppler
      waveforms and flow velocity during respiratory manoeuvres in healthy individuals
      with no liver disease. MATERIALS AND METHODS: In total, 100 individuals (75 women
      and 25 men) without known cardiac or liver disease were examined prospectively
      with duplex Doppler ultrasonography (US). We recorded the Doppler waveforms and
      peak systolic velocities (V(max)) of the middle hepatic vein during normal
      respiration, during breath-holding after quiet expiration and also during deep
      inspiration. Doppler waveforms are categorised as triphasic, biphasic or
      monophasic. RESULTS: During normal respiration, hepatic venous waveforms were
      triphasic in 93% of subjects, monophasic in 6% and biphasic in 1%. During breath
      holding after quiet expiration, the percentages were 91%, 6% and 3%,
      respectively. During deep inspiration, they were 80%, 18% and 2%, respectively.
      Although significant differences were noted between rates during deep inspiration
      and normal respiration, they were quite similar during normal respiration and
      breath-holding after quiet expiration (P<0.05). The values of V(max) were
      significantly higher during normal respiration compared to quiet expiration and
      during quiet expiration compared to deep inspiration (P<0.05). CONCLUSION: The
      velocities and waveforms of hepatic veins varied during respiratory manoeuvres.
      The status of respiration must be taken into consideration whilst examining the
      hepatic vein waveforms and velocities with duplex Doppler US.

PMID- 20138451
TI  - High resolution MR for evaluation of lower urogenital tract malformations in
      infants and children: feasibility and preliminary experiences.
AB  - INTRODUCTION: This retrospective study aimed to assess the value of supplementing
      heavily T2-weighted, high resolution MR-imaging for detailed anatomic assessment
      in paediatric lower urogenital tract (UGT) malformations. PATIENTS/METHODS:
      Sixteen patients (6 male and 10 female, median age=1.8 years, range=0-9 years)
      with suspected malformations of the lower UGT who were retrospectively identified
      from the PACS underwent a clinically indicated standard MR-urography study. In
      order to facilitate a better anatomic assessment of questioned specific lower UGT
      structures, an additional three-dimensional Constructive Interference in Steady
      State-sequence (3D-CISS) had been acquired in these patients. The final diagnosis
      was established by all imaging results and surgical or laprascopic findings. The
      findings from the CISS-sequence were compared to the results from standard MR
      urography for complementary anatomic information and conspicuity. RESULTS:
      Diagnostic 3D-CISS image quality was achieved in all patients. The 3D-CISS
      confirmed an ectopic ureteral insertion in six patients and reliably excluded
      ectopic insertion in 10 patients, whereas conventional MR-urography showed an
      ectopic insertion of the ureter in one case. In six patients with retrovesical
      complex formations (suspicious for an ectopic cystic renal bud or a cystic
      genital structure) the 3D-CISS showed increased conspicuity scores for image
      quality. CONCLUSION: The additional 3D-CISS-sequence increases the diagnostic
      yield in the pelvis in children with complex malformations of the lower UGT such
      as ectopic ureteral insertion or suspected cystic renal or genital malformations
      at only minimal additional time, compared to standard MR-urography.

PMID- 20138452
TI  - Low dose prospective ECG-gated delayed enhanced dual-source computed tomography
      in reperfused acute myocardial infarction comparison with cardiac magnetic
      resonance.
AB  - PURPOSE: To determine whether prospective electrocardiogram (ECG)-gated delayed
      contrast-enhanced dual-source computed tomography (DCE-DSCT) can accurately
      delineate the extension of myocardial infarction (MI) compared with delayed
      enhanced cardiac MR (DE-MR). MATERIAL AND METHODS: Eleven patients were examined
      using dual-source CT and cardiac MR in 2 weeks after a first reperfused MI. DCE
      DSCT scan protocol was performed with prospective ECG-gating sequential scan
      model 7 min after contrast administration. In a 17-model, infarcted myocardium
      detected by DE-MR was categorized as transmural and subendocardial extension.
      Segment of infarcted location and graded transmurality were compared between DCE
      MDCT and DE-MR. RESULTS: In all eleven patients, diagnostic quality was obtained
      for depicting delayed enhanced myocardium. Agreement between DCE-DSCT and MR was
      good on myocardial segment based comparison (kappa=0.85, p<0.001), and on
      transmural and subendocardial infarction type comparison (kappa=0.82, p<0.001,
      kappa=0.52, p<0.001, respectively). CT value was higher on infarcted region than
      that of normal region (100.02+/-9.57 HU vs. 72.63+/-7.32 HU, p<0.001). Radiation
      dose of prospectively ECG-gating protocol were 0.99+/-0.08 mSv (0.82-1.19 mSv).
      CONCLUSIONS: Prospective ECG-gated DCE-DSCT can accurately assess the extension
      and the patterns of myocardial infarction with low radiation dose.

PMID- 20138453
TI  - Analysis of in vitro release through reconstructed human epidermis and synthetic
      membranes of multi-vitamins from cosmetic formulations.
AB  - A convenient method for in vitro investigation of the release of lipid- and water
      soluble vitamins from cosmetic formulations was developed. The permeation of (d)
      alpha-tocopherol (vitamin E), retinyl acetate (pro-vitamin A), ascorbic acid
      (vitamin C) and pyridoxine (vitamin B6) through SkinEthic reconstructed human
      epidermis (RHE), and synthetic polyethersulfone and polycarbonate membranes was
      studied in vitro using a Franz-type diffusion apparatus, coupled either to a
      spectrophotometer for continuous reading (dynamic setting) or to HPLC-DAD
      analysis of the receptor medium (static setting). O/W and W/O emulsions were
      compared with simple aqueous solutions for their kinetic of vitamins release, to
      evaluate the influence of the cosmetic formulation on the bioavailability of
      active ingredients. Results indicate that synthetic membranes offer a limited
      barrier to the diffusion of vitamins, but may provide information on the release
      ability of the formulation. Penetration was more effective when water was the
      external phase of the formulation, i.e. W/O emulsions were less effective in the
      release of vitamins than O/W emulsion or aqueous solutions. RHE (17 days old)
      offered a significantly higher barrier to penetration of vitamins, as expected
      for native human epidermis. The relative ranking in coefficient of permeability
      (Ps (cm/h)) was: ascorbic acid>pyridoxine>>retinyl acetate>alpha-tocopherol
      approximately 0, the absolute values depending on the formulation. The method
      herein described showed to be a practical and convenient tool for the quality
      control and efficacy evaluation of cosmetic formulations.

PMID- 20138454
TI  - Determination of tegafur, 5-fluorouracil, gimeracil and oxonic acid in human
      plasma using liquid chromatography-tandem mass spectrometry.
AB  - S-1 is an oral anticancer drug, which consists of tegafur (FT), gimeracil (CDHP)
      and potassium oxonate (Oxo) at a molar ratio of 1:0.4:1. Among these, tegafur is
      a prodrug, and is rapidly metabolized to the active drug, 5-fluorouracil (5-FU),
      in vivo. To evaluate the pharmacokinetics of S-1 in patients, LC-MS/MS methods
      were developed and validated for determination of FT, 5-FU, CDHP and Oxo in human
      plasma. FT, 5-FU and CDHP were extracted from plasma following protein
      precipitation, separated on a Synergi Hydro-RP column and simultaneously
      quantified by LC-MS/MS. The mobile phase consisted of methanol-water-ammonia
      acetic acid (27:73:0.0018:0.018, v/v/v/v). The mass spectrometer was operated in
      negative mode using electrospray ionization. The calibration curves were linear
      in the range of 12.0-3000ng/mL for FT, and 2.00-500ng/mL for 5-FU and CDHP. The
      accuracy ranged from 93.1% to 110.7% and the precision ranged from 2.4% to 14.6%
      for each analyte. To determine Oxo in human plasma, an LC-MS/MS method employing
      pre-column derivatization was developed and validated. 4-Bromomethyl-7
      methoxycoumarin was chosen as the derivatization reagent and [(13)C(2),(15)N(3)]
      Oxo was used as the internal standard. The MS/MS detection was operated in
      positive mode using an APCI source. The calibration range was 2.00-150ng/mL. The
      accuracy and precision were within 95.9-99.1% and 4.4-10.0%, respectively. The
      validated methods were successfully applied to characterize the pharmacokinetic
      profiles of FT, 5-FU, CDHP and Oxo following oral administration of 60mg S-1
      tablets to patients with solid gastrointestinal tract tumors.

PMID- 20138455
TI  - UPLC-PDA-TOFMS based chemical profiling approach to rapidly evaluate chemical
      consistency between traditional and dispensing granule decoctions of traditional
      medicine combinatorial formulae.
AB  - In the present study, an ultra performance liquid chromatography coupled with
      photo-diode array detector and time-of-flight mass spectrometry (UPLC-PDA-TOFMS)
      based chemical profiling approach to rapidly evaluate chemical consistency
      between traditional and dispensing granule decoctions of traditional medicine
      combinatorial formulae was proposed and validated using San-Huang-Xie-Xin-Tang
      (SHXXT) as a model combinatorial formula. Two different kinds of decoctions,
      namely traditional decoction: water extract of mixed three constituent herbs of
      SHXXT, and dispensing granules decoction: mixed water extract of each individual
      herbs of SHXXT, were prepared. Batches of these two kinds of decoction samples
      were subjected to UPLC-PDA-TOFMS analysis, the datasets of t(R)-m/z pairs, ion
      intensities and sample codes were processed with supervised orthogonal partial
      least squared discriminant analysis (OPLS-DA) to holistically compare the
      difference between these two kinds of decoction samples. Once a clear
      classification trend was found in score plot, further statistics was performed to
      generate S-plot, in which the variables (t(R)-m/z pair) contributing most to the
      difference were clearly depicted as points at the two ends of "S", and the
      components that correlate to these ions were regarded as the most changed
      components during decocting of combinatorial formula. The identities of the
      changed components can be identified by comparing the mass/UV spectra and
      retention times with those of reference compounds and/or tentatively assigned by
      matching empirical molecular formulae with those of the known compounds published
      in the literatures. Using the proposed approach, global chemical difference was
      found between traditional and dispensing granule decoctions, and berberine,
      palmatine, epiberberine, baicalin, wonogoside, 2-O-golloyl-1-O-cinnamoylglucose
      and emodin were identified as the most changed components during decocting SHXXT.
      It is suggested that this newly established approach could be used practically
      for the evaluation of chemical consistency between traditional and dispensing
      granule decoctions of traditional medicine combinatorial formulae.

PMID- 20138456
TI  - GEMMA and MALDI-TOF MS of reactive PEGs for pharmaceutical applications.
AB  - One of the most prominent polymer group applied for drug conjugation is
      poly(ethylene) glycol (PEG). Since drug production is subjected to strict
      restrictions on the part of the FDA and EMEA, also PEG has to be characterized
      accurately. Particularly its molecular mass distribution (MMD) and polydispersity
      can result in unrequested inhomogeneous final products. Therefore evaluation of
      PEG before applying it to drug conjugation is essential. In this study a new
      analytical method for size and molecular mass determination based on
      electrophoretic mobility called GEMMA is used to characterize linear PEGs with
      two differing terminating functional groups. To confirm the data acquired by
      GEMMA a second, well-established method for molecular weight determination, MALDI
      TOF MS (matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry), was applied. Utilizing these two analytical approaches four
      monomethoxylated PEG-succinimidyl succinate (mPEG-SS) derivatives were
      investigated in terms of polydispersity and MMD. Although based on differing
      principles, both analytical methods yield comparable results. All obtained MMD
      maxima for the mPEG-SS batches lie within the company stated specifications,
      MMD+/-10% (based on MALDI-TOF MS data). For mPEG-SS 2K a polydispersity of 1.02
      and for mPEG-SS 5K, 10K and 20K a polydispersity of 1.01 were determined from
      GEMMA as well as from MALDI-TOF MS data and are in agreement with the company's
      data (based on GPC data), namely 1.05-1.10.

PMID- 20138457
TI  - On-line molecular imprinted solid-phase extraction flow-injection fluorescence
      sensor for determination of florfenicol in animal tissues.
AB  - A simple and convenient on-line molecular imprinted solid-phase extraction flow
      injection fluorescence sensor was developed in this study. Florfenicol (FF)
      imprinted polymer was prepared by self-assembly with acrylamide (AM) as
      functional monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker.
      The binding characteristics of the imprinted polymer to florfenicol were
      evaluated by equilibrium binding experiments, and the morphology of the imprinted
      polymer was studied by scanning electron microscope (SEM). Fluorescence intensity
      of 3-p-nitrylphenyl-5-(2'-sulfonophenylazo) rhodanine (4NRASP) and bovine serum
      albumin (BSA) was inhibited by FF. Under optimum conditions the intensity of
      fluorescence shows a linear relationship with the concentration of FF over the
      range of 1.2x10(-6) to 2.6x10(-5)gmL(-1) with a regression equation of
      DeltaI=23.54+17.86c (c 10(-6)gmL(-1)) (r=0.9965, n=6). The low detection limit of
      FF was found to be 3.4x10(-7)gmL(-1) according to 11 parallel determinations for
      the blank solution. The relative standard deviation for the determination of
      2.0x10(-6)gmL(-1) FF solution was 3.5% (n=11). This proposed sensor could be
      satisfactorily applied to the determination of FF in liver and meat samples.

PMID- 20138458
TI  - Isolation and structure characterization of related impurities in 10-O-(N,N
      dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H) bulk drug and
      quantitation by a validated RP-LC.
AB  - 10-O-(N,N-dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H), a novel
      active derivative of ginkgolide B, is a platelet-activating factor antagonist
      which is being under clinical trial. Two unknown related impurities were observed
      in analysis of XQ-1H bulk drug. A scaling up preparative liquid chromatography
      (Prep LC) was used for isolation of the two impurities. Based on LC-MS/MS and
      nuclear magnetic resonance (NMR) spectra, they were characterized as 10-O-(N,N
      dimethylaminoethyl)-11,12-seco-ginkgolide B (imp-1) and 10-O-(N,N
      dimethylaminoethyl)-11,12,2,15-diseco-3,14-dehydroginkgolide B (imp-2),
      respectively. A reversed-phase liquid chromatography (RP-LC) was developed for
      simultaneous determination of XQ-1H as well as imp-1 and imp-2. Main variables
      that significantly influence the chromatographic procedure were optimized and
      efficient chromatographic separation was achieved on a CN column with mobile
      phase consisting of 5mM dipotassium hydrogen phosphate (pH 7.5) and methanol
      delivered in a gradient mode at the flow rate of 1.0mLmin(-1). The method was
      validated and found to be suitable to check the quality of bulk samples of XQ-1H
      at test concentration of 5.0mgmL(-1) for a 20microL injection volume.

PMID- 20138459
TI  - Niacin toxicity resulting from urine drug test evasion.
AB  - BACKGROUND: Niacin, a well-established agent for treating dyslipidemia, has been
      promoted on the Internet as a method for passing urine drug screening, although
      there are no data to support its use for this purpose. In a handful of cases,
      this practice has resulted in serious niacin toxicity. OBJECTIVES: The aim of
      this article is to describe a unique clinical presentation of niacin toxicity.
      CASE REPORT: A 23-year-old previously healthy man presented to an Emergency
      Department with altered mental status, fever, acute renal failure,
      microangiopathic hemolytic anemia, thrombocytopenia, and coagulopathy. It was
      revealed that he had taken approximately 22.5 g of sustained-release niacin over
      the preceding 48 h in an attempt to pass a pre-employment urine drug screen.
      After a complicated hospital course that included mechanical ventilation for
      respiratory failure and hemodialysis for acute renal failure, the patient made a
      full recovery and was discharged 10 days after his initial presentation.
      CONCLUSION: After a massive niacin overdose, the young man in this case presented
      with a complex clinical picture that mimicked concurrent thrombotic
      thrombocytopenic purpura and disseminated intravascular coagulation. Although
      this patient was fortunate to make a full recovery, the case highlights the
      potential for multi-system toxicity with niacin overdose, and the potential for
      harm posed by medical misinformation on the Internet.

PMID- 20138460
TI  - TASER device-induced rhabdomyolysis is unlikely.

PMID- 20138461
TI  - [Pregnancy and pandemic influenza A(H1N1) 2009. Current concepts for anaesthesia
      and critical care medicine].
AB  - Pregnant women are particularly vulnerable to the pandemic influenza A(H1N1)
      2009. Indeed, they are at high risk of developing a severe or fatal form of the
      disease. The physiological changes and the "immune deviation" from cellular to
      humoral immunity occurring during pregnancy are hypotheses to explain this
      vulnerability. Severe forms, mainly viral pneumonias, require an urgent
      prescription of an effective antiviral therapy. Preventive measures, mainly
      vaccination, are essential to avoid the appearance of these severe forms.

PMID- 20138462
TI  - [Hospital reforms: how far will they go?].

PMID- 20138463
TI  - Eye tracking and visual attention to threating stimuli in veterans of the Iraq
      war.
AB  - Theoretical and clinical characterizations of attention in PTSD acknowledge the
      possibility for both hypervigilance and avoidance of trauma-relevant stimuli.
      This study used eye tracking technology to investigate visual orientation and
      attention to traumatic and neutral stimuli in nineteen veterans of the Iraq war.
      Veterans saw slides in which half the screen had a negatively valenced image and
      half had a neutral image. Negatively valenced stimuli were further divided into
      stimuli that varied in trauma relevance (either Iraq war or civilian motor
      vehicle accidents). Veterans reporting relatively higher levels of PSTD symptoms
      had larger pupils to all negatively valenced pictures and spent more time looking
      at them than did veterans lower in PTSD symptoms. Veterans higher in PTSD
      symptoms also showed a trend towards looking first at Iraq images. The findings
      suggest that post-traumatic pathology is associated with vigilance rather than
      avoidance when visually processing negatively valenced and trauma-relevant
      stimuli.

PMID- 20138464
TI  - Chromosomal abnormalities and neuromuscular disorders predict severity and
      outcome of noncompaction in addition to cardiac comorbidities.

PMID- 20138465
TI  - Anomalies associated with a prominent azygos vein on echocardiography in the
      pediatric population.
AB  - BACKGROUND: Prominent azygos veins (PAVs) have been described with interrupted
      inferior venae cavae (IVCs) with heterotaxy. At the authors' institution, cases
      of PAVs with uninterrupted IVCs have been noted. The aim of this study was to
      determine the occurrence rate of PAVs and associated lesions by echocardiography.
      METHODS: All patients with PAVs were collected; those with interrupted and
      uninterrupted IVCs were assigned to groups 1 and 2. Normal controls were assigned
      to group 3. RESULTS: Among 15,849 patients from January 1, 2001, to March 31,
      2008, 55 (0.3%) had PAVs, 42 (76%) in group 1 and 13 (24%) in group 2. Heterotaxy
      was prominent in group 1, whereas patients in group 2 had no heterotaxy. Patients
      in group 2 had more structurally normal hearts than those in group 1 (46% vs 14%,
      P<.01), partial anomalous pulmonary venous return, and one single ventricle. IVC
      measurements were the same in groups 2 and 3 (P=.65). CONCLUSIONS: This study
      demonstrates that a PAV without IVC interruption is not associated with
      heterotaxy. Patients with PAVs should be carefully examined for partial anomalous
      pulmonary venous return.

PMID- 20138466
TI  - Left atrial volume index: a predictor of adverse outcome in patients with
      hypertrophic cardiomyopathy.

PMID- 20138467
TI  - Transthoracic and transesophageal echocardiography for the indication of
      suspected infective endocarditis: vegetations, blood cultures and imaging.
AB  - BACKGROUND: The aim of this study was to investigate the ability of transthoracic
      echocardiography (TTE) to detect vegetations and the relationship between blood
      cultures and transesophageal echocardiography (TEE). METHODS: Five hundred eleven
      TTE and TEE pairs performed to evaluate endocarditis were retrospectively
      analyzed. Vegetation on TTE, prosthetic valve, change in regurgitation, and blood
      cultures were correlated with vegetation on TEE. RESULTS: TTE detected 45% of
      vegetations seen on TEE. There was no difference for prosthetic valves.
      Prosthetic valves (odds ratio, 1.7; P = .03) and increased regurgitation (odds
      ratio, 1.7; P = .01) were associated with vegetations on TEE; staphylococcal
      bacteremia and fungemia were not. Negative blood cultures were associated with
      negative results on TEE (P < .0001), but 27% of patients with prosthetic valves
      had culture-negative endocarditis or nonbacterial thrombotic endocarditis, and 6%
      had abscesses missed by TTE. CONCLUSION: This study demonstrates a limited
      capacity of TTE to detect vegetations. TEE may be an appropriate initial study to
      evaluate prosthetic valves. TEE for culture-negative endocarditis deserves
      further study.

PMID- 20138468
TI  - Prospective assessment of fetal cardiac function with speckle tracking in healthy
      fetuses and recipient fetuses of twin-to-twin transfusion syndrome.
AB  - BACKGROUND: The aim of this study was to assess speckle tracking-derived fetal
      cardiac function in a normal population and in recipient fetuses of twin-to-twin
      transfusion syndrome (TTTS). METHODS: A case-control study was conducted of 59
      uncomplicated singleton pregnancies and 17 recipient fetuses of TTTS. Peak
      systolic strain, strain rate, velocity, and displacement were calculated,
      corrected for gestational age, and compared between patients with TTTS and
      controls. RESULTS: The feasibility of speckle tracking was 83% in controls but
      only 61% in patients with TTTS. Myocardial velocity and displacement increased
      over gestation, and regional differences were present within each wall and
      between walls. Strain and strain rate were stable within each wall but were
      higher in the right ventricle than in the left ventricle and septum. Right
      ventricular strain was decreased in patients with TTTS compared with controls
      (0.75+/-0.34 vs 1.00+/-0.37 multiples of the median, P=.04). CONCLUSION: The
      feasibility of speckle tracking is low when imaging conditions are challenging,
      but it can identify right ventricular failure in selected patients with TTTS.

PMID- 20138469
TI  - High resolution speckle tracking dobutamine stress echocardiography reveals
      heterogeneous responses in different myocardial layers: implication for viability
      assessments.
AB  - BACKGROUND: Speckle-tracking echocardiography (STE) can be used to quantify wall
      strain in 3 dimensions and thus has the potential to improve the identification
      of hypokinetic but viable myocardium on dobutamine stress echocardiography (DSE).
      However, if different myocardial layers respond heterogeneously, STE-DSE will
      have to be standardized according to strain dimension and the positioning of the
      region of interest. Therefore, the aim of this study was to create a high
      resolution model for ejection time (ET) strain and tissue flow in 4 myocardial
      layers at rest, during hypoperfusion, and during dobutamine challenge to assess
      the ability of STE-DSE to detect deformation and functional improvement in
      various layers of the myocardium. METHODS: In 10 open chest pigs, the left
      anterior descending coronary artery was constricted to a constant stenosis,
      resulting in 35% initial flow reduction. Fluorescent microspheres were used to
      measure tissue flow. High-resolution echocardiography was performed epicardially
      to calculate ET strain in 4 myocardial layers in the radial, longitudinal, and
      circumferential directions using speckle-tracking software. Images were obtained
      at rest, during left anterior descending coronary artery constriction
      (hypoperfusion), and during a subsequent dobutamine stress period. RESULTS:
      Dobutamine stress at constant coronary stenosis increased flow in all layers. ET
      strain increased predominantly in the midmyocardial layers in the longitudinal
      and circumferential directions, whereas subendocardial strain did not improve in
      either direction. CONCLUSION: Dobutamine stress influences ET strain differently
      in the various axes and layers of the myocardium and only partially in
      correspondence to tissue flow. Longitudinal and circumferential functional
      reserve opens the potential for the specific detection of midsubendocardial
      viable tissue by high-resolution STE.

PMID- 20138470
TI  - Acquired pulmonary vein stenosis: one problem, two mechanisms.
AB  - Until the last decade, acquired pulmonary vein (PV) stenosis in the adult
      population was a rare finding, caused by neoplasm or inflammatory conditions such
      as sarcoidosis or fibrosing mediastinitis. With the increased use of catheter
      based ablation for the treatment of atrial fibrillation, PV stenosis is
      increasingly recognized as a complication of this procedure. Additionally, PV
      stenosis has been described as a rare complication of cardiac surgery. This
      report describes two cases of PV stenosis, one acquired as a result of multiple
      left atrial ablation procedures and the other after surgical cannulation of the
      right upper PV.

PMID- 20138471
TI  - Sequential changes of longitudinal and radial myocardial deformation indices in
      the healthy neonate heart.
AB  - BACKGROUND: Significant hemodynamic changes, including preload and afterload
      modifications, occur during the transition from the fetal to the neonatal
      environment. The ductus arteriosus closes, pulmonary vascular resistance
      decreases, and pulmonary blood flow increases. Strain rate (SR) and strain
      (epsilon) have been proposed as ultrasound indices for quantifying regional wall
      deformation. This study was designed to determine if these indices can detect
      variations in regional deformation between early and late neonatal periods.
      METHODS: Data were obtained from 30 healthy neonates (15 male). The initial study
      was performed at a mean age of 20.1+/-14 hours (exam 1) and the second at 31.9+/
      2.9 days (exam 2). Apical and parasternal views were used to quantify regional
      left ventricular (LV) and right ventricular (RV) longitudinal and radial SR and
      epsilon, and systolic, early, and late diastolic values were calculated from
      these curves. A paired-samples t test was performed comparing the two groups.
      RESULTS: Compared with exam 1, LV radial deformation showed significant
      reductions in peak systolic epsilon in the basal and mid segments (51+/-15% vs
      46+/-9%, P<.01). LV longitudinal deformation behaved similarly, showing
      significant peak systolic epsilon reductions in all measured segments. Systolic
      SR showed reductions only in the basal and apical segments of the lateral wall
      and in the mid portion of the inferior wall (-1.9+/-0.5 vs -1.7+/-0.3 s(-1) and 
      1.9+/-0.4 vs -1.7+/-0.2 s(-1), respectively, P=.03). RV longitudinal free and
      inferior wall systolic SR and epsilon values were significantly higher in exam 2.
      CONCLUSIONS: LV peak systolic epsilon decreases in exam 2 were possibly due to
      afterload increase and preload decrease. The lower RV initial deformation indices
      could be attributed to increased afterload caused by physiologic pulmonary
      hypertension or immature RV contractile properties. SR seemed to be a more robust
      index than epsilon and less influenced by preload and afterload hemodynamic
      alteration.

PMID- 20138472
TI  - Left atrial electromechanical conduction time can predict six-month maintenance
      of sinus rhythm after electrical cardioversion in persistent atrial fibrillation
      by Doppler tissue echocardiography.
AB  - BACKGROUND: The purpose of this study was to determine whether atrial
      electromechanical conduction time (EMT) measured by echocardiography can predict
      6-month maintenance of sinus rhythm (SR) after electrical cardioversion in
      patients with atrial fibrillation (AF). METHODS: Fifty-three patients with
      persistent AF (>1 month) who had successful cardioversion and 30 controls with SR
      were prospectively enrolled. SR maintenance was assessed during 6-month follow
      up. EMT was measured as the time interval from the onset of the P wave on
      electrocardiography to the peak of the late diastolic wave from the septal and
      lateral mitral annulus (EMT-S and EMT-L, respectively) and the lateral tricuspid
      annulus (EMT-T) on tissue Doppler echocardiography. RESULTS: Compared with
      controls, left atrial (LA) volume index, P-wave duration, and EMT were
      significantly larger in patients with AF (all P values<.001). In patients with
      AF, the duration of AF (P=.71) and P-wave duration (P=.24) were not different
      between the SR maintenance group (n=23) and the AF recurrence group (n=30), and
      there was a trend toward increased LA volume index in the AF recurrence group
      (47.0+/-12.4 vs 45.3+/-12.6 mL/m2, P=.07). EMT-S and EMT-L were significantly
      larger in the AF recurrence group (131.4+/-20.9 vs 116.3+/-15.5 ms, P=.005, and
      152.2+/-15.7 vs 128.9+/-13.8 ms, P<.001, respectively), but not EMT-T. EMT-S and
      EMT-L were related to LA volume index (r=.36, P=.008, and r=.33, P=.02,
      respectively). On multivariate logistic regression analysis, only EMT-L was an
      independent predictor of identifying patients who remained in SR (P<.001), and
      the sensitivity and specificity for the prediction of 6-month maintenance of
      restored SR were 82.6% and 83.3% using a cutoff value of EMT-L<or=138.0 ms (odds
      ratio, 0.862; 95% confidence interval, 0.788-0.942; P=.001). CONCLUSION: LA EMT
      was significantly prolonged in patients with recurring AF, indicating
      significantly depressed atrial conduction in enlarged LA, and can predict 6-month
      maintenance of SR after electrical cardioversion.

PMID- 20138473
TI  - Reliability of visual assessment of global and segmental left ventricular
      function: a multicenter study by the Israeli Echocardiography Research Group.
AB  - BACKGROUND: The purpose of this multicenter study was to determine the
      reliability of visual assessments of segmental wall motion (WM) abnormalities and
      global left ventricular function among highly experienced echocardiographers
      using contemporary echocardiographic technology in patients with a variety of
      cardiac conditions. METHODS: The reliability of visual determinations of left
      ventricular WM and global function was calculated from assessments made by 12
      experienced echocardiographers on 105 echocardiograms recorded using contemporary
      echocardiographic equipment. Ten studies were reread independently to determine
      intraobserver reliability. RESULTS: Interobserver reliability for visual
      differentiation between normal, hypokinetic, and akinetic segments had an
      intraclass correlation coefficient of 0.70. The intraclass correlation
      coefficient for dichotomizing segments into normal versus other abnormal was
      0.63, for hypokinetic versus other scores was 0.26, and for akinetic versus other
      scores was 0.58. Similar results were found for intraobserver reliability.
      Interobserver reliability for WM score index was 0.84 and for left ventricular
      ejection fraction was 0.78. Similar values were obtained for the intraobserver
      reliability of WM score index and ejection fraction. Compared to angiographic
      data, the accuracy of segmental WM assessments was 85%, and correct determination
      of the culprit artery was achieved in 59% of patients with myocardial
      infarctions. CONCLUSION: Among experienced readers using contemporary
      echocardiographic equipment, interobserver and intraobserver reliability was
      reasonable for the visual quantification of normal and akinetic segments but poor
      for hypokinetic segments. Reliability was good for the visual assessment of
      global left ventricular function by WM score index and ejection fraction.

PMID- 20138474
TI  - The treatment of dentinogenic ghost cell tumour.

PMID- 20138475
TI  - Characterization of dendritic cells and macrophages in irritant contact
      dermatitis.

PMID- 20138476
TI  - Carriage of genes for various extended-spectrum beta-lactamases: a novel
      resistance strategy of Klebsiella pneumoniae in Poland.
AB  - Among 110 randomly sampled strains from a collection of 247 extended-spectrum
      beta-lactamase (ESBL)-producing clinical isolates of Klebsiella pneumoniae
      collected from hospitalised children in three paediatric hospitals in Poland, 64
      strains (58.2%) with multiple ESBLs were found, including five non-clonal strains
      (4.5%) harbouring bla genes for ESBLs of three families (CTX-M, SHV and TEM).
      This is the first report of the emergence of triple ESBL-producing K. pneumoniae
      in Poland. In addition, K. pneumoniae strains harbouring bla genes for TEM-130
      and TEM-132 ESBLs were detected in Poland for the first time. Epidemiological
      analysis of the multiple ESBL-producing K. pneumoniae isolates by pulsed-field
      gel electrophoresis (PFGE) revealed a relatively high genetic diversity between
      isolates producing the same combination of enzymes. Clonally related strains were
      uncommon.

PMID- 20138477
TI  - Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi.
AB  - Scrub typhus is a public health concern for a population of over a billion
      humans, with an estimated incidence of one million cases/year in endemic areas.
      Although doxycycline remains the standard therapy, fluoroquinolones have been
      used successfully in a few patients. However, there is also clinical evidence
      that fluoroquinolones are ineffective in the treatment of scrub typhus. To
      clarify this matter, we determined the in vitro susceptibility of Orientia
      tsutsugamushi strain Kato to ciprofloxacin and ofloxacin and sequenced the
      quinolone resistance-determining region (QRDR) of the gyrA gene, the target of
      fluoroquinolones, of 18 fresh isolates from the Lao PDR. Orientia tsutsugamushi
      strain Kato was resistant to ciprofloxacin and ofloxacin in vitro (minimum
      inhibitory concentration=8 microg/mL). All sequences obtained, including those
      from the two available genomes of O. tsutsugamushi (strains Boryong and Ikeda),
      had a Ser83Leu mutation in their QRDR domain that is known to be associated with
      fluoroquinolone resistance. These findings re-emphasise the usefulness of in
      silico analysis for the prediction of antibiotic resistance and suggest that
      fluoroquinolones should not be used in the treatment of scrub typhus.

PMID- 20138478
TI  - CTX-M-35 extended-spectrum beta-lactamase conferring ceftazidime resistance in
      Citrobacter koseri.

PMID- 20138479
TI  - Differentiation of viral and bacterial pneumonia in influenza.

PMID- 20138480
TI  - Geographic distribution of fluoroquinolone-resistant Escherichia coli strains in
      Asia.
AB  - Fluoroquinolone (FQ) resistance is usually caused by point mutations within the
      quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and/or parE.
      However, little is known about the worldwide increase in FQ-resistant Escherichia
      coli or, more specifically, about the geographical distribution of QRDR mutations
      and the clonal spread of isolates. In this study, we analysed 68 FQ-resistant E.
      coli isolates from eight Asian countries using QRDR amino acid mutation patterns
      and examined their susceptibility to FQs. Of the isolates, 38% had mutations at
      S83 and D87 of GyrA and S80 of ParC (MM/-/M-/-) and 34% had mutations at S83 and
      D87 of GyrA, S80 of ParC and S458 of ParE (MM/-/M-/M). MIC(50) values (minimum
      inhibitory concentrations for 50% of the isolates) for isolates with at least
      mutation at S458 of ParE for ciprofloxacin and prulifloxacin were relatively
      higher than MIC(50) values of isolates without this mutation. Based on their
      geographic distribution and the QRDR mutation patterns, the isolates were divided
      into a common type in which the organisms were isolated from three or more
      countries, and a local type in which the isolates were from one or two countries.
      Mutation types at S83L and D87N in GyrA and S80I in ParC with no or another site
      in the QRDR were the most frequent among the FQ-resistant isolates, especially
      among the common type. Gene typing indicated that isolates in the common type
      were not similar between countries. These data suggest that the increase in FQ
      resistant E. coli strains is mainly generated by mutations in the QRDR in each
      geographical area rather than through intercontinental spread.

PMID- 20138481
TI  - High efficacy of clofazimine and its synergistic effect with amikacin against
      rapidly growing mycobacteria.
AB  - The aim of this study was to determine whether clofazimine, dapsone and
      cycloserine may be suitable antimicrobial agents for the treatment of infections
      due to rapidly growing mycobacteria (RGM). The antimicrobial activity of the
      three drugs against 117 Mycobacterium abscessus isolates, 48 Mycobacterium
      fortuitum isolates and 20 Mycobacterium chelonae isolates was evaluated based on
      their broth microdilution minimal inhibitory concentrations (MICs) against the
      isolates. Clofazimine was highly efficacious against these RGM. The vast majority
      of M. abscessus, M. fortuitum and M. chelonae isolates (99.1%, 91.7% and 100%,
      respectively) had clofazimine MICs of <or=1mg/L. MIC(50) values (MIC for 50% of
      the organisms) of clofazimine against the isolates ranged from 0.25mg/L to
      0.5mg/L and MIC(90) values (MIC for 90% of the organisms) ranged from 0.5mg/L to
      1.0mg/L. Cycloserine and dapsone had little or no activity against the isolates.
      The effects of combined application of clofazimine and amikacin on 40 M.
      abscessus isolates, 48 M. fortuitum isolates and 20 M. chelonae isolates were
      evaluated. Addition of 0.25x MIC of amikacin for the isolates to clofazimine
      reduced clofazimine MICs in all of the M. abscessus and M. chelonae isolates and
      in 48% of the M. fortuitum isolates tested. Clofazimine, either alone or combined
      with amikacin, may serve as a promising drug for the treatment of RGM infections.

PMID- 20138482
TI  - Neurobiological correlates of problem gambling in a quasi-realistic blackjack
      scenario as revealed by fMRI.
AB  - In the present study we obtained functional magnetic resonance imaging (fMRI)
      data in occasional gamblers (OG) and problem gamblers (PG) during a quasi
      realistic blackjack game. We focused on neuronal correlates of risk assessment
      and reward processing. Participants had to decide whether to draw or not to draw
      a card in a high-risk or low-risk blackjack situation. We assumed PG would show
      differences in prefrontal and ventral striatal brain regions in comparison to OG
      during risk assessment and due to the winning or losing of money. Although both
      groups did not differ in behavioral data, blood oxygen level dependent (BOLD)
      signals in PG and OG significantly differed in thalamic, inferior frontal, and
      superior temporal regions. Whereas PG demonstrated a consistent signal increase
      during high-risk situations and a decrease in low-risk situations, OG presented
      the opposite pattern. During reward processing as derived from contrasting
      winning vs. losing situations, both PG and OG groups showed an enhancement of
      ventral striatal and posterior cingulate activity. Furthermore, PG demonstrated a
      distinct fronto-parietal activation pattern which has been discussed to reflect a
      cue-induced addiction memory network which was triggered by gambling-related
      cues.

PMID- 20138483
TI  - Enhanced stability of enzyme organophosphate hydrolase interfaced on the carbon
      nanotubes.
AB  - In this paper we demonstrate that SWNTs and a covalent immobilization strategy
      enable very sensitive sensors with excellent long term stability.
      Organophosphorus hydrolase (OPH) functionalized single and multi-walled carbon
      nanotube (CNT) conjugates were exploited for direct amperometric detection of
      paraoxon, a model organophosphate. The catalytic hydrolysis of paraoxon produces
      equimoles of p-nitrophenol; oxidation was monitored amperometrically in real time
      under flow-injection (FIA) mode. OPH covalently immobilized on single-walled
      carbon nanotubes (SWNTs) demonstrated much higher activity than OPH conjugated to
      multi-walled carbon nanotubes (MWNTs). The dynamic concentration range for SWNT
      OPH was 0.5-8.5 micromolL(-1) with a detection limit of 0.01 micromolL(-1)
      (S/N=3). In addition to this high sensitivity, the immobilized OPH retained a
      significant degree of enzymatic activity, and displayed remarkable stability with
      only 25% signal loss over 7 months. These results suggest that covalent
      immobilization of OPH on CNTs can be used for specific immobilization with
      advantages of long term stability, high sensitivity, and simplicity.

PMID- 20138484
TI  - Stress response of fibroblasts adherent to the surface of plasma-treated
      poly(lactic-co-glycolic acid) nanofiber matrices.
AB  - Recent studies have shown that polymeric scaffolds as a synthetic extracellular
      matrix (ECM) are essential for regenerating tissues or organs in tissue
      engineering approaches. Controlling the surface functionality of polymer
      scaffolds is critical in regulation of cellular responses to the scaffolds during
      tissue formation. However, the stress response of cells to polymer scaffolds with
      different surface characteristics is not yet clear. We investigated the
      expression of heat shock protein (HSP) and Bcl-2 in fibroblasts cultured on
      electrospun nanofiber matrices with different surface characteristics. The
      hydrophilicity and chemical composition of electrospun poly(lactic-co-glycolic
      acid) (PLGA) nanofibers was regulated by plasma treatment in the presence of
      ammonia gas. We found that expression levels of HSP and Bcl-2 in fibroblasts were
      strongly dependent on the surface hydrophilicity and concentration of nitrogen
      containing functional groups on the nanofiber matrices. The controlled
      hydrophilicity and surface chemical composition of nanofiber matrices enhanced
      adhesion and spreading of cells on the matrices, resulting in reduction of
      cellular stress. This approach to controlling the surface properties and
      regulating expression of a stress gene could be useful in the design of synthetic
      ECMs for many tissue engineering applications.

PMID- 20138485
TI  - [A case of Kabuki syndrome admitted for acute diarrhea and growth retardation in
      a French hospital in tropical area].
AB  - The authors report on a 6-month-old girl with Kabuki syndrome, admitted for acute
      diarrhoea and growth retardation at the Mayotte hospital. From this case, they
      try to explain the way of understanding and management in front of dysmorphic
      features.

PMID- 20138486
TI  - Classification of functional voice disorders based on phonovibrograms.
AB  - OBJECTIVE: This work presents a computer-aided method for automatically and
      objectively classifying individuals with healthy and dysfunctional vocal fold
      vibration patterns as depicted in clinical high-speed (HS) videos of the larynx.
      METHODS: By employing a specialized image segmentation and vocal fold movement
      visualization technique - namely phonovibrography - a novel set of numerical
      features is derived from laryngeal HS videos capturing the dynamic behavior and
      the symmetry of oscillating vocal folds. In order to assess the discriminatory
      power of the features, a support vector machine is applied to the preprocessed
      data with regard to clinically relevant diagnostic tasks. Finally, the
      classification performance of the learned nonlinear models is evaluated to allow
      for conclusions to be drawn about suitability of features and data resulting from
      different examination paradigms. As a reference, a second feature set is
      determined which corresponds to more traditional voice analysis approaches.
      RESULTS: For the first time an automatic classification of healthy and
      pathological voices could be obtained by analyzing the vibratory patterns of
      vocal folds using phonovibrograms (PVGs). An average classification accuracy of
      approximately 81% was achieved for 2-class discrimination with PVG features. This
      exceeds the results obtained through traditional voice analysis features.
      Furthermore, a relevant influence of phonation frequency on classification
      accuracy was substantiated by the clinical HS data. CONCLUSION: The PVG feature
      extraction and classification approach can be assessed as being promising with
      regard to the diagnosis of functional voice disorders. The obtained results
      indicate that an objective analysis of dysfunctional vocal fold vibration can be
      achieved with considerably high accuracy. Moreover, the PVG classification method
      holds a lot of potential when it comes to the clinical assessment of voice
      pathologies in general, as the diagnostic support can be provided to the voice
      clinician in a timely and reliable manner. Due to the observed interdependency
      between phonation frequency and classification accuracy, in future comparative
      studies of HS recordings of oscillating vocal folds homogeneous frequencies
      should be taken into account during examination.

PMID- 20138487
TI  - Metastatic spinal cord compression: review of the evidence for a radiotherapy
      dose fractionation schedule.
AB  - Metastatic spinal cord compression is a frequent medical emergency, and the most
      common treatment offered is radiotherapy. The routine treatment prescription for
      spinal cord compression in the UK is 20 Gy in five daily fractions delivered over
      1 week. Here, we evaluate the evidence base for the radiotherapy dose for spinal
      cord compression. Evidence from the four prospective studies conducted so far and
      retrospective studies does not support a uniform dose of 20 Gy for all patients
      with spinal cord compression. Available evidence suggests that the radiotherapy
      dose should be tailored to the individual patient, depending on the subtype of
      the tumour, the extent of metastatic disease and expected survival. A risk
      stratification for the optimum dose prescription for patients with spinal cord
      compression is recommended.

PMID- 20138488
TI  - A comparative microanatomical study on cross sections of medial and lateral
      cutaneous nerves of forearm at the antecubital fossa: a cadaveric study.
AB  - BACKGROUND: The anterior branch of the medial antebrachial cutaneous nerve of the
      forearm (AMACN) and the lateral antebrachial cutaneous nerve of the forearm
      (LACN) are used as potential donor grafts for repairing sensory nerves. A higher
      percentage of connective tissue plays an important role in predicting prognosis
      after nerve repair. The aim is to perform a comparative study on cross-sectional
      microanatomy and age related changes in non-fascicular components of the AMACN
      and LACN. METHODS: Thirty six fresh human (from both sides of 14 male and 4
      female) cadaveric AMACN and LACN were collected at antecubital fossae and studied
      at different magnifications for morphometric analysis (total cross-sectional area
      (Asc), fascicular area (Af) and non-fascicular area (Anonf)), after histological
      (Masson's trichrome stain) processing. RESULTS: AMACN and LACN belong to
      polyfascicular type and showed differences in amount of connective and adipose
      tissues in non-fascicular areas. In the AMACN, there was less adipose tissue
      (19.38% in Asc and 25.57% in Anonf) with more collagen fibers (57.28% in Asc and
      75.57% in Anonf) and in the LACN, there was more adipose tissue (47.51% in Asc
      and 58.19% in Anonf) with fewer collagen fibers (34.10% in Asc and 41.76% in
      Anonf) in interfascicular domains. CONCLUSIONS: The amount of adipose tissue in
      LACN non-fascicular area was found to be high at all ages. The presence of less
      adipose tissue and collagen fibers in the non-fascicular area of the AMACN (below
      60 years) could be used for successful nerve grafting when compared to LACN.

PMID- 20138489
TI  - Dentin abnormalities in cheek teeth of wild red deer and roe deer from a fluoride
      polluted area in Central Europe.
AB  - This study analyses the severity and distribution of mineralization defects in
      the dentin of red and roe deer teeth (mandibular fourth premolars, first and
      third molars) obtained from individuals that had lived in a fluoride-polluted
      area along the Czech-German border. Mineralization defects presented as
      hypomineralized or interglobular dentin. In the P(4)s and M(3)s the entire dentin
      exhibited areas of defective mineralization, whereas in the M(1)s only the
      central and inner dentin portions were affected. This suggests that the early
      periods of dentin formation in the first molar, occurring during the late fetal
      and early postnatal (milk-feeding) periods of life, are protected against
      exposure to excess fluoride levels. Our findings are consistent with the
      hypothesis that certain protective mechanisms (partial placental diffusion
      barrier and blood-milk barrier to fluoride, clearance of fluoride from plasma by
      the rapidly growing skeleton) operate during these ontogenetic periods. Studying
      fluoride-induced dentin abnormalities in addition to enamel fluorosis broadens
      the time window during which fluoride effects on the developing dental hard
      tissues can be recorded. Including dentin in the analysis of dental fluorosis
      allows a more detailed reconstruction of lifetime fluoride exposure than would be
      possible by studying enamel fluorosis only, thereby adding to the significance of
      free-ranging deer as bioindicators of fluoride pollution.

PMID- 20138490
TI  - Assessment of the hemorheological profile of koala and echidna.
AB  - Koala, a marsupial, and echidna, a monotreme, are mammals native to Australia.
      Blood viscosity (62.5-1250s(-1)), red blood cell (RBC) deformability, RBC
      aggregation, aggregability and surface charge, and hematological parameters were
      measured in blood samples from six koalas and six echidnas and compared to adult
      human blood. Koala had the largest RBC mean cell volume (107.7+/-2.6fl) compared
      to echidna (81.3+/-2.6fl) and humans (88.4+/-1.2fl). Echidna blood exhibited the
      highest viscosity over the entire range of shear rates. Echidna RBC were
      significantly less deformable than koala RBC but more deformable than human RBC.
      Echidna RBC had significantly lower aggregability (i.e., aggregation in
      standardized dextran medium) than koala or human RBC, while aggregation in
      autologous plasma was similar for the three species. Erythrocyte surface charge
      as indexed by RBC electrophoretic mobility was similar for human and echidna
      cells but was 40% lower for koala RBC. Data obtained during this preliminary
      study indicate that koala and echidna have distinct hemorheological
      characteristics; investigation of these properties may reveal patterns relevant
      to specific behavioral and physiological features of these animals.

PMID- 20138491
TI  - Preselection of patients at risk for COPD by two simple screening questions.
AB  - BACKGROUND: The Burden of Obstructive Lung Disease study showed that in Germany,
      to confirm the diagnosis of chronic obstructive lung disease (COPD) in one
      subject, eight people >= 40 years of age have to be screened. The number-needed
      to-screen (NNS) increased to 18 for identifying a patient with COPD >= GOLD stage
      II. These high numbers limit the cost-effectiveness of COPD screening by
      population spirometry. We investigated in a primary care setting whether using
      two simple questions regarding smoking status and presence of cough and/or
      dyspnea may help to preselect patients for proper diagnosis of COPD. METHODS: A
      total of 1088 patients aged >= 40 yrs without a history of chronic lung disease,
      who were either current or ex-smokers and complained of cough and/or dyspnea,
      were examined by respiratory physicians. Spirometry was carried out to confirm
      COPD diagnosis and severity. RESULTS: A total of 61.6% of patients were male.
      Mean smoking history was 31.8 pack-yrs. In 516 patients (47.4%), a diagnosis of
      COPD was confirmed. Among these, 379 (34.8% of total) had at least GOLD stage II
      COPD, while 89 (8.2% of total) had advanced disease (GOLD stages III/IV). COPD
      prevalence was significantly associated with age and the extent of cigarette
      smoke exposure. CONCLUSIONS: Two questions regarding smoking status and presence
      of cough and/or dyspnea enabled general practitioners to select patients at risk
      for COPD for subsequent spirometry. This preselection reduced the NNS to 2.1 for
      identifying a COPD patient, and to 2.9 for identifying a patient of at least GOLD
      stage II.

PMID- 20138492
TI  - Effects of CPAP therapy on the sympathovagal balance and arterial stiffness in
      obstructive sleep apnea.
AB  - OBJECTIVE: Increased arterial stiffness and sympathovagal imbalance are noted in
      patients with obstructive sleep apnea (OSA). It has been thought that continuous
      positive airway pressure (CPAP) therapy can have beneficial effects on the
      vascular function in such cases. However, it is not yet clear whether the
      improvement of sympathovagal balance by CPAP might be related to reduction of the
      arterial stiffness, independent of changes in the blood pressure. METHODS: In 50
      consecutive eligible patients with OSA (apnea-hypopnea index>/=20/hour) receiving
      CPAP therapy, the brachial-ankle pulse wave velocity (baPWV), heart rate
      variability (LF, HF and LF/HF ratio), baroreceptor sensitivity (BRS), plasma
      levels of C-reactive protein (CRP), and endothelial function as assessed by
      changes in the forearm blood flow before and after reactive hyperemia (END) were
      measured before and after 3-months' CPAP therapy. RESULTS: Significant decrease
      of the LF/HF ratio, plasma levels of CRP, baPWV and heart rate were observed
      after 3 months' CPAP therapy. The change in the baPWV following 3-months' CPAP
      therapy was significantly correlated with the change in the LF/HF ratio and mean
      blood pressure (MBP), but not with that of the BRS, CRP or END after the therapy.
      Multivariate linear regression analysis demonstrated a significant correlation
      between the change in the LF/HF ratio and that in the baPWV (beta=0.305,
      p=0.041), independent of the changes in the MBP, plasma CRP levels and heart
      rate. CONCLUSIONS: Improvement of the sympathovagal balance by CPAP therapy may
      be significantly related to decreased stiffness of the central to middle-sized
      arteries, independent of the changes in the blood pressure and vascular
      endothelial status.

PMID- 20138493
TI  - Mechanical ventilation induces changes in exhaled breath condensate of patients
      without lung injury.
AB  - INTRODUCTION: Measurement of biomarkers in exhaled breath condensate (EBC) may be
      useful for monitoring lung inflammation and injury in mechanically ventilated
      patients. The aim of this study was to analyze changes in biomarkers of
      inflammation in EBC associated with prolonged mechanical ventilation. METHODS:
      EBC samples were collected from critically ill patients weaning from mechanical
      ventilation without lung disease and from healthy nonsmokers. The following
      parameters were measured: pH after helium deaeration, nitrogen oxide and 8
      isoprostane concentrations. RESULTS: EBC was obtained from 10 patients and 20
      controls. Ventilation time before the start of sample collection was 250 (85
      714)h. The post-deaeration pH of EBC samples was significantly lower in
      ventilated patients than controls (7.50 [7.28-7.70] vs 8.07 [7.60-8.40];
      P=0.008). Ventilation time before sample collection inversely correlated with pH
      (r=-0.636; P=0.048). A significantly higher concentration of nitrogen oxide (muM)
      was seen in ventilated patients vs controls (66.22 [22.26-83.13] vs 15.06 [10.73
      23.30]; P=0.002), whereas levels of 8-isoprostane (pg/mL) were not significantly
      different between both groups (5.73 [4.0-11.4] vs 9.09 [6.63-11.43]; P=0.169).
      The nitrogen oxide concentration correlated negatively with dynamic compliance
      (r=-0.952; P<0.001) and positively with respiratory rate (r=0.683; P=0.029).
      CONCLUSIONS: EBC analysis is a non-invasive technique that can be used to monitor
      ventilated patients. Mechanically ventilated patients had higher EBC acidity and
      nitrogen oxide concentrations. Duration of ventilation correlated with breath
      condensate pH.

PMID- 20138494
TI  - Different mechanisms of cis-9,trans-11- and trans-10,cis-12- conjugated linoleic
      acid affecting lipid metabolism in 3T3-L1 cells.
AB  - Conjugated linoleic acid (CLA) has been shown to reduce body fat mass in various
      experimental animals. It is valuable to identify its influence on enzymes
      involved in energy expenditure, apoptosis, fatty acid oxidation and lipolysis. We
      investigated isomer-specific effects of high dose, long treatment of CLA (75.4
      MUmol/L, 8 days) on protein and gene expression of these enzymes in cultured 3T3
      L1 cells. Proteomics identified significant up- or down-regulation of 52 proteins
      by either CLA isomer. Protein and gene expression of uncoupling protein (UCP) 1,
      UCP3, perilipin and peroxisome proliferator-activated receptor (PPAR) alpha
      increased whereas UCP2 reduced for both CLA isomers. And eight-day treatment of
      trans-10,cis-12 CLA, but not cis-9,trans-11 CLA, significantly up-regulated
      protein and mRNA levels of PKA (P<.05), CPT-1 and TNF-alpha (P<.01). Compared to
      protein expression, both isomers did not significantly influence the mRNA
      expression of HSL, ATGL, ACO and leptin. In conclusion, high-dose, long treatment
      of cis-9,trans-11 CLA did not promote apoptosis, fatty acid oxidation and
      lipolysis in adipocytes, but may induce an increase in energy expenditure. trans
      10,cis-12 CLA exhibited greater influence on lipid metabolism, stimulated
      adipocyte energy expenditure, apoptosis and fatty acid oxidation, but its effect
      on lipolysis was not obvious.

PMID- 20138495
TI  - Dietary alpha- and gamma-tocopherol supplementation attenuates lipopolysaccharide
      induced oxidative stress and inflammatory-related responses in an obese mouse
      model of nonalcoholic steatohepatitis.
AB  - Oxidative stress contributes towards the development of nonalcoholic
      steatohepatitis (NASH). Thus, antioxidants may decrease oxidative stress and
      ameliorate the events contributing to NASH. We hypothesized that alpha- or gamma
      tocopherol would protect against lipopolysaccharide (LPS)-triggered NASH in an
      obese (ob/ob) mouse model. Five-week-old obese mice (n=18/dietary treatment) were
      provided 15 mg/kg each of alpha- and gamma-tocopherol or 500 mg/kg of alpha- or
      gamma-tocopherol for 5-weeks. Then, all mice were injected ip once with LPS (250
      MUg/kg) before being sacrificed at 0, 1.5 or 6 h. Body weight and hepatic
      steatosis were unaffected by tocopherols and LPS. Hepatic alpha- and gamma
      tocopherol increased (P<.05) ~9.8- and 10-fold in respective tocopherol
      supplemented mice and decreased in response to LPS. LPS increased serum alanine
      aminotransferase (ALT) by 86% at 6 h and each tocopherol decreased this response
      by 29-31%. By 6 h, LPS increased hepatic malondialdehyde (MDA) and tumor necrosis
      factor-alpha by 81% and 44%, respectively, which were decreased by alpha- or
      gamma-tocopherol. Serum ALT was correlated (P<.05) to hepatic tumor necrosis
      factor-alpha (r=0.585) and MDA (r=0.592), suggesting that inflammation and lipid
      peroxidation contributed to LPS-triggered hepatic injury. alpha- and gamma
      Tocopherol similarly attenuated LPS-triggered increases in serum free fatty acid,
      and alpha-tocopherol only maintained the LPS-triggered serum triacylglycerol
      responses at 6 h. These findings indicate that increasing hepatic alpha- or gamma
      tocopherol protected against LPS-induced NASH by decreasing liver damage, lipid
      peroxidation, and inflammation without affecting body mass or hepatic steatosis.
      Further study is needed to define the mechanisms by which these tocopherols
      protected against LPS-triggered NASH.

PMID- 20138496
TI  - Test methods to aid in the evaluation of the diversion of biodegradable municipal
      waste (BMW) from landfill.
AB  - This response follows on from a recent discussion by Sanchez (2009) on test
      methods to aid in the evaluation of the diversion of biodegradable municipal
      waste (BMW) from landfill. Test methods to assess the
      biodegradability/biodegradable content of organic waste are of great interest
      across Europe for different purposes, such as landfill acceptance criteria,
      monitoring treatment facility performance and for monitoring the diversion of
      biodegradable municipal waste (BMW) from landfill. Many studies have recently
      attempted to correlate short-term test methods with long-term anaerobic test
      methods. This response discusses recent findings and conclusions made by Sanchez
      (2009) and describes recent work undertaken at Cranfield University to develop
      the enzymatic hydrolysis test (EHT) method. The EHT has previously shown
      potential as a short-term, non-biological, biodegradability assessment tool,
      however there is a requirement to further develop this test method. We conclude
      that aerobic and anaerobic biological test methods are not the only suitable
      methods of assessing waste treatment process performance; and that alternative
      methods such as EHT are feasible and potentially suitable.

PMID- 20138497
TI  - Selective organic compounds degradation under controlling composting conditions.
AB  - Organic matter stabilization resulted from the decrease of cellulose, xylan,
      arabinan, acetyl groups, glucuronic acids, galacturonic acids (easily
      biodegradable fractions) and the increase of lignin (resistant compound) and
      humic substances coming from the initial wastes have been studied. A central
      composite experimental design was used to investigate the influence of
      environmental composting parameters (moisture, aeration and particle size) on
      organic matter evolution. The organic matter evolution was clearly influenced by
      the studied composting parameters. All results were concordant, with an increase
      of humic substances and lignin and a decrease of the rest of the cellulose and
      hemicellulose compounds. Lower cellulose, xylan, acetyl groups and glucuronic
      acids contents (higher degradation) have been observed under low particle size
      (1cm) and higher moisture content (70%). However lower lignin and higher humic
      substances under medium (3cm) to low particle size and low moisture content (40%)
      have been found.

PMID- 20138498
TI  - QDs-DNA nanosensor for the detection of hepatitis B virus DNA and the single-base
      mutants.
AB  - We report here a quantum dots-DNA (QDs-DNA) nanosensor based on fluorescence
      resonance energy transfer (FRET) for the detection of the target DNA and single
      mismatch in hepatitis B virus (HBV) gene. The proposed one-pot DNA detection
      method is simple, rapid and efficient due to the elimination of the washing and
      separation steps. In this study, the water-soluble CdSe/ZnS QDs were prepared by
      replacing the trioctylphosphine oxide (TOPO) on the surface of QDs with 3
      mercaptopropionic acid (MPA). Subsequently, oligonucleotides were attached to the
      QDs surface to form functional QDs-DNA conjugates. Along with the addition of DNA
      targets and Cy5-modified signal DNAs into the QDs-DNA conjugates, sandwiched
      hybrids were formed. The resulting assembly brings the Cy5 fluorophore, the
      acceptor, and the QDs, the donor, into proximity, leading to fluorescence
      emission from the acceptor by means of FRET on illumination of the donor. In
      order to efficiently detect single-base mutants in HBV gene, oligonucleotide
      ligation assay was employed. If there existed a single-base mismatch, which could
      be recognized by the ligase, the detection probe was not ligated and no Cy5
      emission was produced due to the lack of FRET. The feasibility of the proposed
      method was also demonstrated in the detection of synthetic 30-mer oliginucleotide
      targets derived from the HBV with a sensitivity of 4.0nM by using a multilabel
      counter. The method enables a simple and efficient detection that could be
      potentially used for high throughput and multiplex detections of target DNA and
      the mutants.

PMID- 20138499
TI  - Direct colorimetric diagnosis of pathogen infections by utilizing thiol-labeled
      PCR primers and unmodified gold nanoparticles.
AB  - We describe here a greatly simplified colorimetric detection method to identify
      PCR-amplified nucleic acids. Our method relies on the PCR product having thiol
      group at one end, which is generated by employing thiolated PCR primer. After PCR
      amplification reaction, unmodified gold nanoparticles (AuNPs) are added into the
      reaction tube followed by the addition of NaCl to induce the aggregation of
      AuNPs. The PCR products strongly bind to the surface of AuNPs through the
      interaction of the terminal thiol groups and the long chain of DNA which has
      abundant negative charges enhances the electrostatic and steric repulsion among
      AuNPs, which consequently leads to the prevention of the salt-induced
      aggregation. As a result, the color of AuNPs remains red in the presence of the
      PCR-amplified nucleic acids, while the AuNPs change its color from red to blue
      due to the salt-induced aggregation in the absence of the PCR products. This
      simple but very efficient colorimetric strategy was successfully demonstrated by
      diagnosing Chlamydia infection using a real human urine sample. Since the results
      can be clearly seen with the naked eye without any complicated step such as
      surface modification of AuNPs or PCR product purification, this method can be
      easily applied to point-of-care diagnosis.

PMID- 20138500
TI  - Origin and analysis of microbial population heterogeneity in bioprocesses.
AB  - Heterogeneity of industrial production cultures is accepted to a certain degree;
      however, the underlying mechanisms are seldom perceived or included in the
      development of new bioprocess control strategies. Population heterogeneity and
      its basics, perceptible in the diverse proficiency of cells, begins with
      asymmetric birth and is found to recess during the life cycle. Since inefficient
      subpopulations have significant impact on the productivity of industrial
      cultures, cellular heterogeneity needs to be detected and quantified by using
      high speed detection tools like flow cytometry. Possible origins of population
      heterogeneity, sophisticated fluorescent techniques for detection of individual
      cell states, and cutting-edge Omics-technologies for extended information beyond
      the resolution of fluorescent labelling are highlighted.

PMID- 20138501
TI  - A technique for stereotactic radiosurgery treatment planning with helical
      tomotherapy.
AB  - The purpose of this study was to develop an efficient and effective planning
      technique for stereotactic radiosurgery using helical tomotherapy. Planning CTs
      and contours of 20 patients, previously treated in our clinic for brain
      metastases with linac-based radiosurgery using circular collimators, were used to
      develop a robust TomoTherapy planning technique. Plan calculation times as well
      as delivery times were recorded for all patients to allow for an efficiency
      evaluation. In addition, conformation and homogeneity indices were calculated as
      metrics to compare plan quality with that which is achieved with conventional
      radiosurgery delivery systems. A robust and efficient planning technique was
      identified to produce plans of radiosurgical quality using the TomoTherapy
      treatment planning system. Dose calculation did not exceed a few hours and
      resulting delivery times were less than 1 hour, which allows the process to fit
      into a single day radiosurgery workflow. Plan conformity compared favorably with
      published results for gamma knife radiosurgery. In addition, plan homogeneity was
      similar to linac-based approaches. The TomoTherapy planning software can be used
      to create plans of acceptable quality for stereotactic radiosurgery in a time
      that is appropriate for a radiosurgery workflow that requires that planning and
      delivery occur within 1 treatment day.

PMID- 20138502
TI  - Mechanisms that regulate the number of neurons during mouse neocortical
      development.
AB  - Cortical development progresses through an early phase of progenitor expansion, a
      middle phase of neurogenesis, and a final phase of gliogenesis. During the middle
      phase, the neurogenic phase, the neocortical primordium balances the production
      of neurons against the maintenance of neural precursor cells (NPCs). The final
      number of neurons is determined by the duration of the neurogenic phase, the rate
      of NPC division, and the mode of NPC division, that is, whether a division gives
      rise to two NPCs, one NPC and one cell committed to the neuronal lineage, or two
      committed cells. We discuss here recent advances in understanding these key
      aspects that are fundamental for normal brain development.

PMID- 20138503
TI  - Understanding biology by stretching proteins: recent progress.
AB  - Single molecule manipulation techniques combined with molecular dynamics
      simulations and protein engineering have enabled, during the last decade, the
      mechanical properties of proteins to be studied directly, thereby giving birth to
      the field of protein nanomechanics. Recent data obtained from such techniques
      have helped gain insight into the structural bases of protein resistance against
      forced unfolding, as well as revealing structural motifs involved in mechanical
      stability. Also, important technical developments have provided new perspectives
      into protein folding. Eventually, new and exciting data have shown that
      mechanical properties are key factors in cell signaling and pathologies, and have
      been used to rationally tune these properties in a variety of proteins.

PMID- 20138504
TI  - Predictive biomarkers for personalised anti-cancer drug use: discovery to
      clinical implementation.
AB  - A priority translational research objective in cancer medicine is the discovery
      of novel therapeutic targets for solid tumours. Ideally, co-discovery of
      predictive biomarkers occurs in parallel to facilitate clinical development of
      agents and ultimately personalise clinical use. However, the identification of
      clinically useful predictive biomarkers for solid tumours has proven challenging
      with many initially promising biomarkers failing to translate into clinically
      useful applications. In particular, the 'failure' of a predictive biomarker has
      often only become apparent at a relatively late stage in investigation. Recently,
      the field has recognised the need to develop a robust clinical biomarker
      development methodology to facilitate the process. This review discusses the
      recent progress in this area focusing on the key stages in the biomarker
      development process: discovery, validation, qualification and implementation.
      Concentrating on predictive biomarkers for selecting systemic therapies for
      individual patients in the clinic, the advances and progress in each of these
      stages in biomarker development are outlined and the key remaining challenges are
      discussed. Specific examples are discussed to illustrate the challenges
      identified and how they have been addressed. Overall, we find that significant
      progress has been made towards a formalised biomarker developmental process. This
      holds considerable promise for facilitating the translation of predictive
      biomarkers from discovery to clinical implementation. Further enhancements could
      eventually be found through alignment with regulatory processes.

PMID- 20138505
TI  - Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer
      impair survival? A meta-analysis.
AB  - BACKGROUND: In stage III colorectal cancer (CRC), adjuvant chemotherapy (CT) is
      usually prescribed within two months after curative surgery. Whether or not
      delaying initiation of CT affects survival is still debated. MATERIAL AND
      METHODS: We performed a meta-analysis (MA) of all published studies (full papers
      or abstracts) comparing delayed CT with standard care. Studies were obtained from
      a PubMed query (keywords: CRC, adjuvant treatment, delay of CT), a review (Chau
      et al., 2006), cross-checking references and abstracts from the proceedings of
      ASCO, ASCO GI and WCGI annual meetings. We chose a cutoff delay of 8 weeks. Risk
      Ratios (RRs) were calculated from the recorded events (deaths, relapses). We used
      EasyMA software (fixed-effect model). RESULTS: Fourteen studies (including four
      abstracts) were identified (17,645 patients; 5,952 males, 5,151 females, mean age
      70 years). Of these, three could not be statistically analysed and three used
      another cutoff (4, 5 or 6 weeks), leaving 8 studies for main MA (13,158 patients;
      3,932 males, 3,644 females, 5,942 missing data; 5,576 colon cancers, 6,677
      rectal, 1,265 missing data). Delaying CT more than 8 weeks was associated to
      worse Overall Survival (OS) (RR: 1.20; 95% Confidence Interval (CI) 1.15-1.26).
      In the MA including all studies whatever their cutoff, longer delay was similarly
      associated to a worse OS but not a worse Relapse-Free Survival (RFS) (five
      studies). CONCLUSION: Adjuvant chemotherapy should be started within 8 weeks
      after surgery. Delaying the initiation of adjuvant CT for more than 8 weeks after
      surgery significantly decreased OS but not RFS. This discrepancy might be due to
      factors not directly related to cancer (post-operative complications, social
      status) or to a more accurate appraisal of death.

PMID- 20138506
TI  - Questionnaires and instruments for a multidimensional assessment of the older
      cancer patient: what clinicians need to know?
AB  - Due to the ageing of the population in the Western world, a significant increase
      in the number of older patients diagnosed with neoplastic diseases is observed.
      Hence, there is an emerging need for tools to efficiently evaluate older
      patients' functional and global status. These tools can allow treating
      oncologists to better select patients, to propose treatment modifications,
      implement supportive measures and develop interventions to decrease the risk of
      toxicity and in general better tailor the treatment plan on an individual level.
      Currently significant uncertainty exists about the optimal tools and strategy for
      geriatric assessment, but on the other hand there is more than enough evidence
      that (some form of) geriatric assessment detects many previously unrecognised
      problems, and allows directed intervention which can improve outcome and
      compliance of proposed treatments. In the present paper, we discuss the most
      commonly used and studied tools for the assessment of functional status of older
      cancer patients.

PMID- 20138507
TI  - Future treatment of soft tissue sarcomas will be driven by histological subtype
      and molecular aberrations.
AB  - Soft tissue sarcomas, although sharing a mesenchymal origin, are a heterogeneous
      group of diseases. Nevertheless they are studied and frequently treated as if
      they were all the same. Recent developments suggest that a different approach may
      be more adequate. Genetic profiling studies have indicated that some soft tissue
      sarcoma subtypes, despite a distinct histo-pathological difference, may be
      closely related. Molecular biology research in addition has identified several
      subtype-specific oncogenes and their protein products that could serve as
      treatment targets. Since many of the new molecularly targeted agents do not
      induce tumour regression, but mainly result in growth inhibition, it is therefore
      necessary also to change the study end-point in screening studies in the search
      for active treatments. In view of all these it is proposed to consider using
      alternative end-points such as progression-free rates at pre-set times, or
      progression arrest at first evaluation. By using databases from large cooperative
      groups it should be possible to identify progression arrest rates for each
      specific subtype, and these could serve as reference for future trial design.
      Soft tissue sarcoma treatment and research will require a change of approach and
      necessitate global cooperation.

PMID- 20138508
TI  - Kinetic evaluation and performance of a mesophilic anaerobic contact reactor
      treating medium-strength food-processing wastewater.
AB  - High rate mesophilic anaerobic contact reactors (MACR) represent a proven
      sustainable technology for a wide range of different industrial effluents. These
      reactors demonstrate quite similar features to their aerobic counterparts,
      activated sludge systems. A lab-scale high rate mesophilic anaerobic contact
      reactor was operated with wastewater originated from a potato-processing plant,
      at six different loading rates of 1.1-5g COD/L per day. The operational
      performance of MACR was monitored from start-up by assessing COD removal
      efficiency, total volatile fatty acid production and biogas composition.
      Furthermore, various kinetic models have been successfully applied to the
      experimental data to determine substrate balance, maximum utilization rate and
      volumetric methane production. The COD removal efficiencies were found to be 78
      92% and the methane percentage of the biogas produced was 80-89%. Additionally,
      the methane yield coefficient was found to be 0.394 L CH(4)/gTCOD(rem).

PMID- 20138509
TI  - Conversion of cassava wastes for biofertilizer production using phosphate
      solubilizing fungi.
AB  - Two fungi characterized as Aspergillus fumigatus and Aspergillus niger, isolated
      from decaying cassava peels were used to convert cassava wastes by the semi-solid
      fermentation technique to phosphate biofertilizer. The isolates solubilized
      Ca(3)(PO(4))(2), AlPO(4) and FePO(4) in liquid Pikovskaya medium, a process that
      was accompanied by acid production. Medium for the SSF fermentation was composed
      of 1% raw cassava starch and 3% poultry droppings as nutrients and 96% ground
      (0.5-1.5mm) dried cassava peels as carrier material. During the 14days
      fermentation, both test organisms increased in biomass in this medium as
      indicated by increases in phosphatase activity and drop in pH. Ground cassava
      peels satisfied many properties required of carrier material particularly in
      respect of the organisms under study. Biofertilizer produced using A. niger
      significantly (p<.05) improved the growth of pigeon pea [Cajanus cajan (L.)
      Millsp.] in pot experiments but product made with A. fumigatus did not.

PMID- 20138510
TI  - 2-Amino-aryl-7-aryl-benzoxazoles as potent, selective and orally available JAK2
      inhibitors.
AB  - A series of novel benzoxazole derivatives has been designed and shown to exhibit
      attractive JAK2 inhibitory profiles in biochemical and cellular assays, capable
      of delivering compounds with favorable PK properties in rats. Synthesis and
      structure-activity relationship data are also provided.

PMID- 20138511
TI  - Biochemical analysis of cellular target of S-trityl-L-cysteine derivatives using
      affinity matrix.
AB  - Biochemical analysis of the cellular target of S-trityl-l-cysteine (STLC)
      derivatives was performed by using the newly synthesized STLC derivative
      immobilized affinity beads (3d). The affinity beads efficiently captured KSP in
      HCT116 cytoplasmic cell lysate. The results obtained from pull-down and
      competition experiments using 3d with STLC derivatives provided the first
      evidence for direct interaction of these derivatives with KSP in cancer cells.
      Design, synthesis and application of 3d were reported.

PMID- 20138512
TI  - Discovery of potent and bioavailable GSK-3beta inhibitors.
AB  - Here we report on the discovery of a series of maleimides which have high potency
      and good selectivity for GSK-3beta. The incorporation of polar groups afforded
      compounds with good bioavailability. The most potent compound 34 has an IC(50) of
      0.6nM for GSK-3beta, over 100-fold selectivity against a panel of other kinases,
      and shows efficacy in rat osteoporosis models. The X-ray structure of GSK-3beta
      protein with 34 bound revealed the binding mode of the template and provided
      insights for future optimization opportunities.

PMID- 20138513
TI  - N1-Alkyl pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse
      transcriptase.
AB  - A series of N1-alkyl pyrimidinediones were designed, synthesized and evaluated as
      HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Our efforts
      identified compound 10b, which represents the lead compound in this series with
      pharmacokinetics and antiviral potency that may support once-daily dosing.

PMID- 20138514
TI  - 3-Aryl-4-(arylhydrazono)-1H-pyrazol-5-ones: Highly ligand efficient and potent
      inhibitors of GSK3beta.
AB  - A series of 3-aryl-4-(arylhydrazono)-1H-pyrazol-5-one inhibitors of GSK3beta was
      developed from a low molecular weight, highly ligand efficient screening hit 1.
      Hit-to-lead optimization led to a number of highly potent inhibitors, while
      maintaining the high ligand efficiency of the screening hit.

PMID- 20138515
TI  - Synthesis and in vitro evaluation of (18)F-labelled S-fluoroalkyl
      diarylguanidines: Novel high-affinity NMDA receptor antagonists for imaging with
      PET.
AB  - Two S-[(18)F]fluoroalkylated diarylguanidines were synthesized and evaluated in
      vitro as potential tracers for imaging of N-methyl-d-aspartate receptors (NMDARs)
      with positron emission tomography (PET). [(18)F]1 and [(18)F]10 were synthesized
      by [(18)F]fluoroethylation and [(18)F]fluoromethylation of the thiol precursor 6,
      respectively. [(18)F]1 is a promising candidate NMDAR PET tracer, with low
      nanomolar affinity for the NMDA PCP-site, high selectivity and moderate
      lipophilicity.

PMID- 20138516
TI  - Discovery of potent and selective bicyclic A(2B) adenosine receptor antagonists
      via bioisosteric amide replacement.
AB  - Several new potent and selective A(2B) adenosine receptor antagonists have been
      prepared in which the aryl-amide moiety of the lead series, exemplified by 1a,
      has been replaced by bioisosteric bicyclic moieties. Although the majority of
      compounds had generally improved microsomal stability as compared to 1a, this was
      not translated into overall improvements in the pharmacokinetic profiles of a
      representative set of compounds.

PMID- 20138517
TI  - Stereospecific synthesis of oximes and oxime ethers of 3-azabicycles: A SAR study
      towards antimicrobial agents.
AB  - Libraries of 1-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O
      methyloximes 1-14/15-28/29-42 and 7-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9
      ones/oximes/O-methyloximes 43-48/49-54/55-60 were synthesized and their
      stereochemistry was established by 1D/2D NMR spectral and single crystal XRD
      studies. All the synthesized oximes and oxime ethers were screened for their in
      vitro antimicrobial activity against a panel of pathogenic bacteria (Bacillus
      subtilis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas
      aeruginosa) and fungi (Candida albicans, Candida parapsilosis, Aspergillus niger
      and Cryptococcus neoformans) using Gentamicin and Fluconazole as standards,
      respectively. From the SAR profile, the lead molecules were identified.

PMID- 20138518
TI  - Preparation and in vitro screening of symmetrical bispyridinium cholinesterase
      inhibitors bearing different connecting linkage-initial study for Myasthenia
      gravis implications.
AB  - Reversible inhibitors (e.g., pyridostigmine bromide, neostigmine bromide) of
      carbamate origin are used in the early treatment of Myasthenia gravis (MG) to
      block acetylcholinesterase (AChE) native function and conserve efficient amount
      of acetylcholine for decreasing number of nicotinic receptors. Carbamate
      inhibitors are known for many undesirable side effects related to the reversible
      inhibition of AChE. In contrast, this paper describes 20 newly prepared
      bispyridinium inhibitors of potential concern for MG. Although some compounds
      from this series have been known before, they were not assayed for cholinesterase
      inhibition yet. The newly prepared compounds were evaluated in vitro on human
      erythrocyte AChE and human plasmatic butyrylcholinesterase (BChE). Their
      inhibitory ability was expressed as IC(50) and compared to standard carbamate
      drugs. Three compounds presented promising inhibition (in muM range) of both
      enzymes in vitro similar to the used standards. The novel inhibitors did not
      present selectivity between AChE and BChE. Two newly prepared compounds were
      chosen for docking studies and confirmed apparent pi-pi or pi-cationic
      interactions aside enzyme's catalytic sites. The kinetics assay confirmed non
      competitive inhibition of AChE by two best newly prepared compounds.

PMID- 20138519
TI  - Novel molecular hybrids of cinnamic acids and guanylhydrazones as potential
      antitubercular agents.
AB  - In an attempt to identify potential new agents active against tuberculosis, 20
      novel phenylacrylamide derivatives incorporating cinnamic acids and
      guanylhydrazones were synthesized using microwave assisted synthesis. Activity of
      the synthesized compounds was evaluated using resazurin microtitre plate assay
      (REMA) against Mycobacterium tuberculosis H37Rv. Based on empirical structure
      activity relationship data it was observed that both steric and electronic
      parameters play major role in the activity of this series of compounds. Compound
      7s (2E)-N-((-2-(3,4-dimethoxybenzylidene) hydrazinyl) (imino) methyl)-3-(4
      methoxyphenyl) acrylamide showed MIC of 6.49microM along with good safety profile
      of >50-fold in VERO cell line. Thus, this compound could act as a potential lead
      for further antitubercular studies.

PMID- 20138520
TI  - The role of phosphate in the action of thymidine phosphorylase inhibitors:
      Implications for the catalytic mechanism.
AB  - The design and synthesis of 5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil
      (AIFU), a potent inhibitor of thymidine phosphorylase (TP) with K(i)-values of
      11nM (ecTP) and 17nM (hTP), are described. Kinetic studies established that the
      type of inhibition of TP by AIFU is uncompetitive with respect to inorganic
      phosphate (or arsenate). The results obtained suggest that AIFU and other
      zwitterionic thymine analog inhibitors of TP act as transition state analogs,
      mimicking the anionic thymine leaving group, consistent with an S(N)2-type
      catalytic mechanism, and anchored by their protonated side chains to the enzyme
      bound phosphate by electrostatic and H-bonding interactions.

PMID- 20138521
TI  - Development of improved inhibitors of wall teichoic acid biosynthesis with potent
      activity against Staphylococcus aureus.
AB  - A small molecule (1835F03) that inhibits Staphylococcus aureus wall teichoic acid
      biosynthesis, a proposed antibiotic target, has been discovered. Rapid, parallel,
      solution-phase synthesis was employed to generate a focused library of analogs,
      providing detailed information about structure-activity relationships and leading
      to the identification of targocil, a potent antibiotic.

PMID- 20138522
TI  - The ubiquitin code of yeast permease trafficking.
AB  - Yeast permeases, that act as transporters for nutrients including amino acids,
      nucleobases and metals, provide a powerful model system for dissecting the
      physiological control of membrane protein trafficking. Modification of these
      transporters by ubiquitin is known to target them for degradation in the vacuole,
      the degradation organelle of fungi. Recent studies have uncovered the role of
      specific adaptors for recruiting the Rsp5 ubiquitin ligase to these proteins. In
      addition, the role of ubiquitin at different trafficking steps including early
      endocytosis, sorting into the multivesicular body (MVB) pathway and Golgi-to
      endosome transit is now becoming clear. In particular, K63-linked ubiquitin
      chains now emerge as a specific signal for protein sorting into the MVB pathway.
      A complete view of the ubiquitin code governing yeast permease trafficking might
      not be far off.

PMID- 20138523
TI  - Indicators of dynamic stability in transtibial prosthesis users.
AB  - An improved understanding of factors related to dynamic stability in lower-limb
      prosthesis users is important, given the high occurrence of falls in this
      population. Current methods of assessing stability are unable to adequately
      characterize dynamic stability over a variety of walking conditions. F-Scan
      Mobile has been used to collect plantar pressure data and six extracted
      parameters were useful measures of dynamic stability. The aim of this study was
      to investigate dynamic stability in individuals with unilateral transtibial
      amputation based on these six parameters. Twenty community ambulators with a
      unilateral transtibial amputation walked over level ground, uneven ground,
      stairs, and a ramp while plantar pressure data were collected. For each limb
      (intact and prosthetic) and condition, six stability parameters related to
      plantar center-of-pressure perturbations and gait temporal parameters, were
      computed from the plantar pressure data. Parameter values were compared between
      limbs, walking condition, and groups (unilateral transtibial prosthesis users and
      able-bodied subjects). Differences in parameters were found between limbs and
      conditions, and between prosthesis users and able-bodied individuals. Further
      research could investigate optimizing parameter calculations for unilateral
      transtibial prosthesis users and define relationships between potential for falls
      and the dynamic stability measures.

PMID- 20138524
TI  - Classifying household and locomotive activities using a triaxial accelerometer.
AB  - The purpose of this study was to develop a new algorithm for classifying physical
      activity into either locomotive or household activities using a triaxial
      accelerometer. Sixty-six volunteers (31 men and 35 women) participated in this
      study and were separated randomly into validation and cross-validation groups.
      All subjects performed 12 physical activities (personal computer work, laundry,
      dishwashing, moving a small load, vacuuming, slow walking, normal walking, brisk
      walking, normal walking while carrying a bag, jogging, ascending stairs and
      descending stairs) while wearing a triaxial accelerometer in a controlled
      laboratory setting. Each of the three signals from the triaxial accelerometer was
      passed through a second-order Butterworth high-pass filter to remove the
      gravitational acceleration component from the signal. The cut-off frequency was
      set at 0.7 Hz based on frequency analysis of the movements conducted. The ratios
      of unfiltered to filtered total acceleration (TAU/TAF) and filtered vertical to
      horizontal acceleration (VAF/HAF) were calculated to determine the cut-off value
      for classification of household and locomotive activities. When the TAU/TAF
      discrimination cut-off value derived from the validation group was applied to the
      cross-validation group, the average percentage of correct discrimination was
      98.7%. When the VAF/HAF value similarly derived was applied to the cross
      validation group, there was relatively high accuracy but the lowest percentage of
      correct discrimination was 63.6% (moving a small load). These findings suggest
      that our new algorithm using the TAU/TAF cut-off value can accurately classify
      household and locomotive activities.

PMID- 20138525
TI  - A multivariate analysis of prognostic factors for health-related quality of life
      in patients with surgically managed meningioma.
AB  - The objective of this study was to examine the prognostic significance of health
      related quality of life (HQOL) parameters combined with baseline clinical factors
      in patients undergoing neurosurgery for treatment of meningioma. A total of 147
      patients (61 male, 86 female; mean age 43 years, range 5-77 years) who underwent
      resection of a meningioma between January 2002 and December 2004 were studied.
      HQOL was evaluated using a modified questionnaire based on the World Health
      Organization Quality of Life-100 Scale and the Karnofsky Performance Scale. The
      relationships between HQOL and clinical history, radiological findings, extent of
      resection, histological grade and recurrence were investigated using multivariate
      analysis. The mean HQOL score was 73.94+/-1.79 for preoperative patients with
      meningioma, 84.88+/-2.14 for postoperative patients, and 91.13+/-1.61 for healthy
      controls. HQOL for patients with meningioma was significantly lower than that for
      normal controls (P<0.001), and postoperative patients had a more satisfactory
      HQOL than preoperative (P<0.05). Cox proportional hazards analysis showed that
      significant predictors of health-related quality of life were tumor size, extent
      of surgical excision, and histologic grade. Multivariate backward logistic
      regression yielded the regression equation HQOL=119.1097 - 1.5002X(3) -
      8.6650X(6) - 10.4210X(7) (R=0.7466; where X(3) is tumor size, X(6) is extent of
      surgical excision, and X(7) is the histologic grade of the tumor). This equation
      can be used preoperatively to predict the HQOL of meningioma patients after
      neurosurgery. A specialized HQOL questionnaire for patients with meningioma
      provides useful information when planning the operative procedure, and may make
      it more likely that patients have a satisfactory HQOL after surgery.

PMID- 20138526
TI  - S-Arachidonoyl-2-thioglycerol synthesis and use for fluorimetric and colorimetric
      assays of monoacylglycerol lipase.
AB  - We report the first synthesis of 2-thioglycerol and S-arachidonoyl-2-thioglycerol
      (the thioester analog of the endocannabinoid 2-arachidonoylglycerol) in an eight
      or nine step procedure with a yield of approximately 25% and establish the use of
      this substrate for maleimide-based fluorescent and dithiobis(2-nitrobenzoic acid)
      based colorimetric assays of human recombinant monoacylglycerol (MAG) lipase
      (hMAGL) and human brain membrane MAG hydrolase activity. Inhibitor structure
      activity relationships observed here for hMAGL and 2-ATG correlate well
      (r(2)=0.93, n=9) with earlier findings for mouse brain MAG hydrolase with non
      thiol substrates.

PMID- 20138527
TI  - Synthesis and biological screening of a combinatorial library of beta-chlorovinyl
      chalcones as anticancer, anti-inflammatory and antimicrobial agents.
AB  - A combinatorial library of beta-chlorovinyl chalcones (4) were synthesized by
      Claisen-Schmidt condensation reaction. Catalytic reaction of substituted 3-chloro
      3-phenyl-propenal (2) and 1-(2,4-dimethoxy-phenyl)-ethanone or 1-(4-methoxy
      phenyl)-ethanone (3) in alkaline conditions furnished the target compound 5
      chloro-1-(2,4-dimethoxy-phenyl)-5-phenyl-penta-2,4-dien-1-one (4). The
      synthesized compounds were screened for their biological activity viz.
      anticancer, anti-inflammatory and antimicrobial activities. Synthesized compounds
      4g and 4h revealed promising anti-inflammatory activity (66-67% TNF-alpha and 95
      97% IL-6 inhibitory activity at 10 microM). Cytotoxicity of the compounds checked
      using CCK-8 cell lines and found to be nontoxic to slightly toxic. Furthermore,
      the anticancer activity (30-40%) was shown by compounds 4d, 4e, 4h and 4b at 10
      microM concentrations against ACHN followed by Calu 1, Panc1, HCT116 and H460
      cell lines. Some of the compounds 4d, 4e, 4a, 4i and 4b revealed promising
      antimicrobial activity at MIC 50-100 microg/mL against selected pathogenic
      bacteria and fungi.

PMID- 20138528
TI  - Geometry corrections for cylindrical neutron area survey meters.
AB  - MCNP calculations have been performed to investigate the effects of beam
      divergence on the response of selected cylindrical neutron area survey meters
      irradiated by selected neutron sources. By comparing the results to calculations
      performed using plane-parallel beam irradiations, geometry correction factors
      have been calculated that can be applied to instrument calibrations. The results
      indicate that the effective centres of cylindrical detectors may not lie on the
      axis of symmetry, as previously assumed.

PMID- 20138529
TI  - Development of simulated air filters for gamma-ray spectrometry proficiency
      testing.
AB  - A set of 60 spiked simulated air filter sources was developed for the 2004-2005
      proficiency test of the Italian radioactivity surveillance network. Each
      simulated filter source was prepared by reproducible volumetric dispensing of 19
      drops of a mixed radioactive solution containing Co-57, Cs-134, Cs-137, Co-60 and
      Eu-152. The spiking pattern was investigated and optimized by numerical
      simulations. The filter sources were checked by double counting on HPGe and
      NaI(Tl) detectors. The standard deviation (SD) of activity values was 1.5%.

PMID- 20138530
TI  - Syncytium gene expression in Glycine max([PI 88788]) roots undergoing a resistant
      reaction to the parasitic nematode Heterodera glycines.
AB  - The plant parasitic nematode, Heterodera glycines is the major pathogen of
      Glycine max (soybean). H. glycines accomplish parasitism by creating a nurse cell
      known as the syncytium from which it feeds. The syncytium undergoes two
      developmental phases. The first is a parasitism phase where feeding sites are
      selected, initiating the development of the syncytium. During this earlier phase
      (1-4 days post infection), syncytia undergoing resistant and susceptible
      reactions appear the same. The second phase is when the resistance response
      becomes evident (between 4 and 6dpi) and is completed by 9dpi. Analysis of the
      resistant reaction of G. max genotype PI 88788 (G. max([PI 88788])) to H.
      glycines population NL1-RHg/HG-type 7 (H. glycines([NL1-RHg/HG-type 7])) is
      accomplished by laser microdissection of syncytia at 3, 6 and 9dpi. Comparative
      analyses are made to pericycle and their neighboring cells isolated from mock
      inoculated roots. These analyses reveal induced levels of the jasmonic acid
      biosynthesis and 13-lipoxygenase pathways. Direct comparative analyses were also
      made of syncytia at 6 days post infection to those at 3dpi (base line). The
      comparative analyses were done to identify localized gene expression that
      characterizes the resistance phase of the resistant reaction. The most highly
      induced pathways include components of jasmonic acid biosynthesis, 13
      lipoxygenase pathway, S-adenosyl methionine pathway, phenylpropanoid
      biosynthesis, suberin biosynthesis, adenosylmethionine biosynthesis, ethylene
      biosynthesis from methionine, flavonoid biosynthesis and the methionine salvage
      pathway. In comparative analyses of 9dpi to 6dpi (base line), these pathways,
      along with coumarin biosynthesis, cellulose biosynthesis and homogalacturonan
      degradation are induced. The experiments presented here strongly implicate the
      jasmonic acid defense pathway as a factor involved in the localized resistant
      reaction of G. max([PI 88788]) to H. glycines([NL1-RHg/HG-type 7]).

PMID- 20138531
TI  - Postoperative atrial fibrillation in patients undergoing aortocoronary bypass
      surgery carries an eightfold risk of future atrial fibrillation and a doubled
      cardiovascular mortality.
AB  - OBJECTIVE: This article presents a study of postoperative atrial fibrillation
      (AF) and its long-term effects on mortality and heart rhythm. METHODS: The study
      cohort consisted of 571 patients with no history of AF who underwent primary
      aortocoronary bypass surgery from 1999 to 2000. Postoperative AF occurred in
      165/571 patients (28.9%). After a median follow-up of 6 years, questionnaires
      were obtained from 91.6% of surviving patients and an electrocardiogram (ECG)
      from 88.6% of all patients. Data from hospitalisations due to arrhythmia or
      stroke during follow-up were analysed. The causes of death were obtained for
      deceased patients. RESULTS: In postoperative AF patients, 25.4% had atrial
      fibrillation at follow-up compared with 3.6% of patients with no AF at surgery
      (p<0.001). An episode of postoperative AF was the strongest independent risk
      factor for development of late AF, with an adjusted risk ratio of 8.31 (95%
      confidence interval (CI) 4.20-16.43). Mortality was 29.7% (49 deaths/165
      patients) in the AF group and 14.8% (60 deaths/406 patients) in the non-AF group
      (p<0.001). Death due to cerebral ischaemia was more common in the postoperative
      AF group (4.2% vs 0.2%, p<0.001), as was death due to myocardial infarction (6.7%
      vs 3.0%, p=0.041). Postoperative AF was an age-independent risk factor for late
      mortality, with an adjusted hazard ratio of 1.57 (95% CI 1.05-2.34). CONCLUSIONS:
      Postoperative AF patients have an eightfold increased risk of developing AF in
      the future, and a doubled long-term cardiovascular mortality.

PMID- 20138532
TI  - Fontan completion in patients with atrial isomerism and separate hepatic venous
      drainage.
AB  - OBJECTIVE: Fontan completion in patients with atrial isomerism, in which the
      inferior vena cava (IVC) and the hepatic vein (HV) drain separately, is
      technically challenging. Herein, we review our surgical approach to these
      patients. METHODS: The medical records of 50 consecutive patients with atrial
      isomerism who underwent Fontan completion between 1998 and 2008 were reviewed
      retrospectively. RESULTS: Separate HV drainage was present in 17 patients.
      Patients with interrupted IVC were excluded. Patient characteristics were as
      follows: median age, 26 months (range 15-149); median weight, 9.6 kg (range 8.1
      47.2); right atrial isomerism, 16 patients; and left atrial isomerism, one. The
      IVC and the separate HV at the level of diaphragm were contralateral in 16
      patients, and ipsilateral in one. The surgical procedures for directing blood
      flow from the IVC and the separate HV to the pulmonary arteries were as follows:
      en bloc resection of the IVC and the HV and anastomosing these veins to an
      extracardiac conduit in 10 patients; connecting the IVC to the HV in a side-to
      side fashion before anastomosing them to an extracardiac conduit in one; and
      lateral tunnel in another. When the IVC and the HV were widely separated by the
      vertebrae, we chose an intra-extracardiac conduit (intra-atrial septation) in
      four patients and an extracardiac conduit for the IVC and the right HV and
      lateral tunnel for the separate left HV in one. There was no mortality. Five re
      operations were performed (pacemaker in two patients; one each of fenestration,
      release of outflow obstruction and ligation of collateral arteries). Sixteen
      patients underwent follow-up catheterisation, which revealed central venous
      pressure of 12.0 + or - 2.0 mmHg and arterial oxygen saturation of 92% + or - 6%.
      CONCLUSIONS: The mid-term results of the Fontan completion in patients with
      atrial isomerism and separate HV drainage were excellent. The distance between
      the IVC and the separate HV and the position of the vertebrae should be
      considered when choosing a surgical technique.

PMID- 20138533
TI  - Correction of leaflet prolapse extends the spectrum of patients suitable for
      valve-sparing aortic root replacement.
AB  - OBJECTIVE: Preservation of the native aortic valve in patients requiring aortic
      root replacement avoids the need for lifelong anticoagulation and potentially
      offers greater durability than a bio-prosthetic valve. Such techniques have
      generally been applied to patients with early grades of aortic regurgitation (AR)
      and less severe aortic root dilatation where leaflets have been minimally
      stretched. We reviewed our experience with these techniques and in particular the
      durability of the addition of leaflet prolapse correction in patients with more
      advanced aortic root pathology compared to those with non-prolapsing leaflets.
      METHODS: A total of 61 patients with tri-leaflet valves underwent valve-sparing
      aortic root replacement, of which 42 (69%) had leaflet prolapse correction. There
      were 48 (79%) males and mean age was 61 + or - 13 years. The majority of patients
      had either severe AR secondary to aortic root dilatation or aortic root
      aneurysms. Grade 3+ or 4+ AR was present in 47 (77%) patients. The re
      implantation technique was performed in 53 (87%) patients and the remodelling in
      eight (13%) patients. Concomitant cardiac procedures were performed in 29 (48%)
      patients including aortic arch reconstruction in 15 (25%). RESULTS: There were
      three (4.9%) in-hospital and one late death. Mean follow-up was 28 + or - 26
      months and was 98% complete. Five patients developed grade 3 or 4 AR, of whom
      three required aortic valve replacement (AVR), which was performed uneventfully.
      Five-year survival was 95 + or - 2.8%. Freedom from AR was 88 + or - 5.3% and
      freedom from AVR was 93 + or - 4.1% at 5 years. Patients who had correction of
      leaflet prolapse experienced equivalent freedom from significant AR to those who
      did not require it. CONCLUSION: Patients with large aortic root aneurysms and
      advanced AR often have stretched leaflets that will prolapse and lead to early
      failure if only root geometry is corrected. With the addition of leaflet prolapse
      correction, we have shown equivalent durability to those without stretched
      leaflets. This has allowed valve preservation in a sizable subgroup who would
      otherwise have received prosthetic valves. Greater patient numbers and longer
      follow-up are needed to fully validate this approach.

PMID- 20138534
TI  - Surgical assessment of malignant pleural mesothelioma: have we reached a critical
      stage?
AB  - OBJECTIVE: The International Mesothelioma Interest Group (IMIG) classification is
      the most widely used staging system but is based on post-resectional parameters.
      We aimed to test the association between clinical and pathological staging and to
      identify possible discrepancies. METHODS: We identified 164 consecutive patients
      (144 males and 20 females, with mean age 58 years) who underwent radical surgery
      (114 extrapleural pneumonectomy; 50 radical pleurectomy/decortication) for
      malignant pleural mesothelioma (MPM). The patients were clinically staged with CT
      + or - MRI (CT, computed tomography; MRI, magnetic resonance imaging). RESULTS:
      Clinical T (cT) stage proved to be the same as pathological T (pT) stage in 44%;
      understaged in 46% and overstaged in 10%. Clinical N (cN) stage proved to be the
      same as pathological N (pN) stage in 56%; understaged in 31% and overstaged in
      13%. Disease-free interval (DFI) was associated with cT stage (median DFI 29
      months, SE 13, 95% CI 3-54 months for cT1; median 5, SE 3, 95% CI 3-6 months for
      cT4, p=0.02) but not clinical N stage (median DFI 12 months, SE 1, 95% CI 9-15
      months for cN0; median DFI 11 months, SE 0.3, 95% CI 10-12 months for cN2, p=0.5)
      and was associated with both pT (median DFI 31 months, SE 17, 95% CI 0-64 months
      for pT1; median DFI 8 months, SE1, 95% CI 6-11 months for pT4, p=0.03) and pN
      stage (median DFI 14 months, SE 3, 95% CI 9-20 months for pN0; median DFI 10
      months, SE 1, 95% CI 8-13 months for pN2, p=0.02). Overall survival was
      associated with cT stage (median survival 25 months, SE 3, 95% CI 20-30 months
      for cT1; median survival 11 months, SE 3, 95% CI 10-11 months for cT4, p=0.01)
      but not cN stage (median survival 15 months, SE 2, 95% CI 11-19 months for cN0;
      median survival 15 months, SE 2, 95% CI 12-19 months for cN2, p=0.49) and pN
      stage (median survival 22 months, SE 3, 95% CI 19-27 months for pN0; median
      survival 14 months, SE 1, 95% CI 12-17 months for pN2, p=0.01) but not pT stage
      (median survival 27 months, SE 4, 95% CI 19-35 months for pT1; median survival 12
      months, SE 2, 95% CI 9-15 months for pT4, p=0.06). Pathological IMIG stage was
      associated with DFI and overall survival; however, preoperative IMIG stage was
      less useful. CONCLUSIONS: There are deficiencies in the current staging system
      for MPM and discrepancies between clinical and pathological systems. Future
      improvements are needed in clinical descriptors of nodal status and pathological
      descriptors of T stage. Subsequent IMIG stage grouping also needs revision.

PMID- 20138535
TI  - Giant unruptured non-coronary sinus of Valsalva aneurysm presenting as tricuspid
      stenosis.

PMID- 20138536
TI  - A simplified surgical approach for aortic valve replacement after previous
      coronary artery bypass grafting using upper mini-sternotomy approach.

PMID- 20138537
TI  - Cerebral functions and metabolism after antegrade selective cerebral perfusion in
      aortic arch surgery.
AB  - OBJECTIVES: Antegrade selective cerebral perfusion (ASCP) represents the best
      method of cerebral protection during surgery of the thoracic aorta. However,
      brain integrity and metabolism after antegrade cerebral perfusion have not yet
      been investigated. We assessed cerebral positron emission tomography (PET),
      diffusion-weighted imaging, proton magnetic resonance spectroscopy and cognitive
      functions in patients undergoing either ASCP or coronary artery bypass grafting
      (CABG) to elucidate whether cerebral perfusion was associated with postoperative
      neuronal alterations, metabolic deficit or cognitive decline. METHODS: Seventeen
      patients undergoing aortic arch surgery using ASCP with moderate hypothermia (26
      degrees C) (ASCP group) and 15 patients undergoing elective on-pump CABG (CABG
      group) were prospectively enrolled in the study. Brain PET, diffusion-weighted
      imaging, proton magnetic resonance spectroscopy and neuropsychometric testing
      were performed preoperatively, and at 1 week and 6 months postoperatively (T1, T2
      and T3, respectively). Patient data were compared for statistic analysis with a
      normal database made up of healthy subjects. RESULTS: One patient in each group
      was excluded because they refused postoperative evaluation. There were neither
      strokes nor hospital deaths. Two patients suffered from temporary neurological
      dysfunction (one in each group). Proton magnetic resonance spectroscopy did not
      reveal significant alterations in cortical N-acetyl-aspartate (NAA) content
      within and between the groups at T2 and T3. In the ASCP group, brain diffusion
      weighted magnetic resonance showed a significant increase of the apparent
      diffusion coefficient values, reflecting vasogenic cerebral oedema, at T2, that
      disappeared at T3. Magnetic resonance detected new focal brain lesions in two
      CABG group patients. In seven ASCP group patients, PET scan showed glucose
      hypometabolism in the occipital lobes at T2, which disappeared in five patients
      at successive examination (T3). Significant cognitive decline was not observed in
      any patient. Test score changes between and within groups were not significant.
      CONCLUSIONS: There was no evidence of ischaemic brain injury after ASCP even if
      some degree of reversible brain oedema secondary to cardiopulmonary bypass (CPB)
      was present. The cognitive outcomes in patients undergoing ASCP were comparable
      to patients undergoing coronary artery bypass. The lack of left subclavian artery
      perfusion during cerebral perfusion leads to temporary glucose hypometabolism in
      the occipital lobes without neuronal injury.

PMID- 20138538
TI  - Using ultra-weak photon emission to determine the effect of oligomeric
      proanthocyanidins on oxidative stress of human skin.
AB  - Exposure of skin to ultraviolet (UV) radiation triggers oxidative stress in skin
      tissue that can lead to erythema, early skin aging or even cancer. It is
      suggested that oligomeric proanthocyanidins (OPCs), phytonutrients that belong to
      the polyphenol family have an anti-oxidant/anti-inflammatory activity on the
      skin. Measuring ultra-weak photon emission (UPE) is a non-invasive, fairly
      sensitive and convenient technique for continuously monitoring oxidative stress.
      The present study was undertaken to confirm anti-oxidant activity of the specific
      OPCs cream formulation in human skin by measuring UPE of skin. In the present
      study 25 healthy female subjects participated. As a baseline measurement of skin,
      UPE was recorded from the dorsal surface of the subjects' hands before
      (spontaneous UPE) and after exposure to UV (UV-induced UPE). The effects of the
      OPCs cream on spontaneous and UV-induced UPE were measured using a fractionated
      UV exposure protocol. UV exposure resulted in an increase in UPE from both hands.
      Repeat UV exposure also resulted in a long-term increase of spontaneous UPE. This
      is likely due to depletion of anti-oxidant capacity of skin resulting in
      sensitization of skin to UV. It was assessed by measuring spontaneous UPE at 80
      min after each UV exposure. Application of the OPCs cream immediately after UV
      exposure resulted in a significant (approx. 30%) decrease in UV-induced UPE.
      Topical OPCs cream application also reduced sensitization of skin to UV following
      repeated UV exposure (i.e., reduced long-term increase in spontaneous UPE). This
      study indicates that the specific OPCs cream formulation significantly decreases
      UV-induced oxidative stress in human skin based on UPE measurement. It therefore
      suggests that regular use of this OPCs cream might protect skin from harmful
      effects of UV.

PMID- 20138539
TI  - Colon cancer.
AB  - Colon cancer is one of the leading tumours in the world and it is considered
      among the big killers, together with lung, prostate and breast cancer. In the
      recent years very important advances occurred in the field of treatment of this
      frequent disease: adjuvant chemotherapy was demonstrated to be effective, chiefly
      in stage III patients, and surgery was optimized in order to achieve the best
      results with a low morbidity. Several new target-oriented drugs are under
      evaluation and some of them (cetuximab and bevacizumab) have already exhibited a
      good activity/efficacy, mainly in combination with chemotherapy. The development
      of updated recommendations for the best management of these patients is crucial
      in order to obtain the best results, not only in clinical research but also in
      every-day practice. This report summarizes the most important achievements in
      this field and provides the readers useful suggestions for their professional
      practice.

PMID- 20138540
TI  - Genomic Grade Index: An important tool for assessing breast cancer tumor grade
      and prognosis.
AB  - Different multi-gene expression signatures have been shown to outperform classic
      histopathologic variables and therefore represent an important step towards
      personalizing breast cancer treatment. In particular, gene profiles overcome many
      of the limitations observed with classic histopathologic variables. The Genomic
      Grade Index (GGI) is a gene expression signature developed to better define
      histologic grade assessment. GGI divides classic histologic grade into low and
      high risk, instead of grades 1, 2 and 3. The ability of GGI to predict response
      to chemotherapy and separate hormone receptor positive breast cancer subtypes has
      also been demonstrated. This article critically reviews the limitations inherent
      in classic histologic grade evaluation; it also reviews the process of gene
      signature development in general and then focuses on GGI, its biologic
      significance, comparison with different gene signatures, and its applicability to
      clinical practise.

PMID- 20138541
TI  - Tomorrow's targeted therapies in breast cancer patients: what is the risk for
      increased radiation-induced cardiac toxicity?
AB  - Ongoing clinical trials are now investigating the benefits of new targeted
      therapies, including ErbB and tyrosine kinase inhibitors (TKI) and
      antiangiogenics. Those may carry a potential risk for additional cardiac
      toxicity, particularly in association with radiotherapy. Although the risk of
      symptomatic cardiotoxicity is low, more subtle functional declines may increase
      mortality with longer follow-up and necessitate caution when assessing concurrent
      or sequential trastuzumab or lapatinib with radiotherapy. Potential additive
      toxicity encourages more conformal irradiation modalities minimizing cardiac
      dose, such as gating, intensity-modulated radiotherapy or Helical Tomotherapy. We
      recommend the collection of substantial information relevant to cardiac
      radiotoxicity in further clinical trials of targeted agents in breast cancer
      treatment, including doses delivered to cardiac structures, especially the
      coronary arteries. The incorporation of new biomarkers or modalities for
      assessment of cardiac function may also become necessary to detect cardiac
      toxicity at earliest stage.

PMID- 20138542
TI  - Partners in crime: deregulation of AR activity and androgen synthesis in prostate
      cancer.
AB  - Prostate cancer remains a leading cause of cancer death, as there are no durable
      means to treat advanced disease. Treatment of non-organ-confined prostate cancer
      hinges on its androgen dependence. First-line therapeutic strategies suppress
      androgen receptor (AR) activity, via androgen ablation and direct AR antagonists,
      whereas initially effective, incurable, 'castration-resistant' tumors arise as a
      result of resurgent AR activity. Alterations of AR and/or associated regulatory
      networks are known to restore receptor activity and support resultant therapy
      resistant tumor progression. However, recent evidence also reveals an unexpected
      contribution of the AR ligand, indicating that alterations in pathways
      controlling androgen synthesis support castration-resistant AR activity. In this
      report, the mechanisms underlying the lethal pairing of AR deregulation and
      aberrant androgen synthesis in prostate cancer progression will be discussed.

PMID- 20138543
TI  - Fragmentation of alpha-radical cations of arginine-containing peptides.
AB  - Fragmentation pathways of peptide radical cations, M(+*), with well-defined
      initial location of the radical site were explored using collision-induced
      dissociation (CID) experiments. Peptide radical cations were produced by gas
      phase fragmentation of Co(III)(salen)-peptide complexes [salen = N,N'-ethylenebis
      (salicylideneiminato)]. Subsequent hydrogen abstraction from the beta-carbon of
      the side-chain followed by C(alpha)-C(beta) bond cleavage results in the loss of
      a neutral side chain and formation of an alpha-radical cation with the radical
      site localized on the alpha-carbon of the backbone. Similar CID spectra dominated
      by radical-driven dissociation products were obtained for a number of arginine
      containing alpha-radicals, suggesting that for these systems radical migration
      precedes fragmentation. In contrast, proton-driven fragmentation dominates CID
      spectra of alpha-radicals produced via the loss of the arginine side chain.
      Radical-driven fragmentation of large M(+*) peptide radical cations is dominated
      by side-chain losses, formation of even-electron a-ions and odd-electron x-ions
      resulting from C(alpha)-C bond cleavages, formation of odd-electron z-ions, and
      loss of the N-terminal residue. In contrast, charge-driven fragmentation produces
      even-electron y-ions and odd-electron b-ions.

PMID- 20138544
TI  - Evolution of innate and adaptive immune recognition structures.

PMID- 20138545
TI  - Cryoablation of osteoid osteoma: two case reports.
AB  - Contemporary treatment of osteoid osteoma involves percutaneous imaging-guided
      therapy. Radiofrequency ablation (under computed tomographic guidance) remains
      the standard of care. Herein, the authors describe the successful treatment of
      two osteoid osteomas by using percutaneous cryoablation in difficult-to-access
      areas.

PMID- 20138546
TI  - Hydronephrosis after embolization of internal iliac artery aneurysms.
AB  - The treatment of internal iliac artery aneurysms is aimed at the prevention of
      rupture. Traditionally, this is undertaken surgically; however, endovascular
      techniques are an acceptable alternative and these techniques are also not
      without complication. Herein, the authors describe the endovascular treatment of
      two patients with internal iliac aneurysms. Although the treatments were
      initially successful, both patients presented with ureteric obstruction and
      hydronephrosis 2 months later.

PMID- 20138547
TI  - Treatment of symptomatic focal nodular hyperplasia with percutaneous
      radiofrequency ablation.
AB  - The authors report a case of a 21-year-old woman taking oral contraceptives for
      severe dysmenorrhea who presented with a hepatic mass and worsening right upper
      quadrant pain. The oral contraceptives could not be discontinued because of her
      pelvic symptoms, necessitating treatment of the liver lesion for symptomatic
      relief. Computed tomography and percutaneous biopsy demonstrated the mass to be
      focal nodular hyperplasia. The patient opted for radiofrequency ablation rather
      than surgical enucleation for symptomatic relief. The ablation proved to be a
      safe and effective alternative to surgery to treat the benign tumor, and
      permitted more aggressive therapy of the dysmenorrhea.

PMID- 20138548
TI  - One-lung ventilation can alter the severity of aortic regurgitation.

PMID- 20138549
TI  - Cerebrospinal fluid drainage with bivalirudin and rFactor VIIa for thoracic
      aortic aneurysm surgery using left atrial-femoral artery bypass.

PMID- 20138550
TI  - Difficult management of anticoagulation with argatroban in a patient undergoing
      on-pump cardiac surgery.

PMID- 20138551
TI  - Assessment of surgical septal myectomy by real-time 3-dimensional transesophageal
      echocardiography.

PMID- 20138552
TI  - Global interference and spatial uncertainty in the Sustained Attention to
      Response Task (SART).
AB  - The Sustained Attention to Response Task (SART) is a Go-No-Go signal detection
      task developed to measure lapses of sustained conscious attention. In this study,
      we examined the impact global interference and spatial uncertainty has on SART
      performance. Ten participants performed either a SART (high-Go) or a
      traditionally formatted (low-Go) version of a global-local stimuli detection task
      with spatially certain and uncertain signals. Reaction time in the SART was
      insensitive to global interference and spatial uncertainty, whereas reaction time
      in the low-Go task was sensitive. Spatial uncertainty increased errors of
      omission in the SART, which was not expected if the SART measures mindlessness.
      There was a high correlation between participants' errors of commission rate and
      their reaction time in the SART. The results, overall, support the view that the
      SART is a better measure of response strategy than lapses in sustained attention
      or mindlessness.

PMID- 20138553
TI  - POLG DNA testing as an emerging standard of care before instituting valproic acid
      therapy for pediatric seizure disorders.
AB  - PURPOSE: To review our clinical experience and determine if there are appropriate
      signs and symptoms to consider POLG sequencing prior to valproic acid (VPA)
      dosing in patients with seizures. METHODS: Four patients who developed VPA
      induced hepatotoxicity were examined for POLG sequence variations. A subsequent
      chart review was used to describe clinical course prior to and after VPA dosing.
      RESULTS: Four patients of multiple different ethnicities, age 3-18 years,
      developed VPA-induced hepatotoxicity. All were given VPA due to intractable
      partial seizures. Three of the patients had developed epilepsia partialis
      continua. The time from VPA exposure to liver failure was between 2 and 3 months.
      Liver failure was reversible in one patient. Molecular studies revealed
      homozygous p.R597W or p.A467T mutations in two patients. The other two patients
      showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S.
      Clinical findings and POLG mutations were diagnostic of Alpers-Huttenlocher
      syndrome. CONCLUSION: Our cases underscore several important findings: POLG
      mutations have been observed in every ethnic group studied to date; early
      predominance of epileptiform discharges over the occipital region is common in
      POLG-induced epilepsy; the EEG and MRI findings varying between patients and
      stages of the disease; and VPA dosing at any stage of Alpers-Huttenlocher
      syndrome can precipitate liver failure. Our data support an emerging proposal
      that POLG gene testing should be considered in any child or adolescent who
      presents or develops intractable seizures with or without status epilepticus or
      epilepsia partialis continua, particularly when there is a history of psychomotor
      regression.

PMID- 20138554
TI  - Lung function measurement of single lungs by lung area segmentation on 2D dynamic
      MRI.
AB  - RATIONALE AND OBJECTIVES: Most lung disease is inhomogeneously distributed but
      diagnosed by global spirometry. Regional lung function might allow for earlier
      diagnosis. Dynamic two-dimensional magnetic resonance imaging (2D-MRI) can depict
      lung motion with high temporal resolution. We evaluated whether measurement of
      lung area on dynamic 2D-MRI has sufficient agreement with spirometry to allow for
      lung function testing of single lungs. MATERIAL AND METHODS: Ten healthy
      volunteers were examined in a 1.5 T MRI scanner with a Flash 2D-sequence (8.5
      images per second, sagittal and coronal orientation) with simultaneous
      spirometry. The lung area was segmented semiautomatically and the area changes
      were compared with spirometric volume changes. RESULTS: Segmentation of one time
      series took 191 seconds on average. Volume-time and flow-volume curves from MRI
      data were almost congruent with spirometric curves. Pearson correlation of MRI
      area with spirometry was very high (mean correlation coefficients >0.97). Bland
      Altman plots showed good agreement of lung area with spirometry (95% limits of
      agreement below 11% in each direction). Differences between lung area and
      spirometry were significantly smaller for sagittal measurement of the right lung
      than sagittal measurement of the left lung and coronal measurement. The relative
      forced expiratory volume in the first second differed less than 5% between MRI
      and spirometry in all but one volunteer. CONCLUSIONS: Measurement of lung area on
      2D-MRI allows for functional measurement of single lungs with good agreement to
      spirometry. Postprocessing is fast enough for application in a clinical context
      and possibly provides increased sensitivity for lung functional measurement of
      inhomogeneously distributed lung disease.

PMID- 20138555
TI  - Thoughts on the ethics of preventing and controlling epizootic diseases.

PMID- 20138556
TI  - Meta-analysis and functional effects of the SLC30A8 rs13266634 polymorphism on
      isolated human pancreatic islets.
AB  - BACKGROUND: The C-allele of rs13266634 located in SLC30A8 (ZNT8) has been
      strongly associated with decreased insulin release and with type 2 diabetes (T2D)
      susceptibility in some but not all studies. To shed further light on this issue,
      we performed a meta-analysis of the association between rs13266634 and T2D in
      different ethnic groups and assessed the relationships between SLC30A8 genotypes
      and some properties of isolated human islets. METHODS: From 32 original articles,
      a total of 77,234 control individuals and 44,945 subjects with T2D were studied
      in meta-analysis. To assess the relationships between SLC30A8 genotype and islet
      cell phenotype, insulin secretion in response to glucose, glucose plus arginine
      and glucose plus glibenclamide was determined in pancreatic islets isolated from
      82 multiorgan donors genotyped for the rs13266634 polymorphism. Quantitative
      expression of SLC30A8, Insulin and Glucagon mRNA was also measured. RESULTS:
      Overall, each SLC30A8 risk allele was associated with a 14% increased risk for
      T2D (P=2.78 x 10(-34)). The population risk of T2D attributable to this
      polymorphism was estimated at 9.5% in Europeans and 8.1% in East Asians. Basal
      and stimulated insulin secretion from human islets as well as islet expressions
      of SLC30A8, Insulin and Glucagon were not affected by the presence of the
      polymorphism. However, SLC30A8 expression was positively correlated with Insulin
      (r=0.75, P=6.43 x 10(-6)) and Glucagon (r: 0.70, P=4.89 x 10(-5)) levels.
      CONCLUSIONS: The SLC30A8 rs13266634 polymorphism is among the most confirmed
      genetic markers of T2D in Europeans and East Asians. In isolated human islets,
      the risk C-allele does not affect ex-vivo insulin secretion and SLC30A8
      expression, which is correlated with that of insulin and glucagon.

PMID- 20138557
TI  - Identification and characterization of a novel homozygous deletion in the alpha-N
      acetylglucosaminidase gene in a patient with Sanfilippo type B syndrome
      (mucopolysaccharidosis IIIB).
AB  - Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is an autosomal recessive
      disease that is caused by a deficiency of the lysosomal enzyme alpha-N
      acetylglucosaminidase (NAGLU). Over 100 different mutations in the NAGLU gene
      have been identified in Sanfilippo syndrome type B patients; however, no large
      deletions have been reported. Here we present the first case of a large
      homozygous intragenic NAGLU gene deletion identified in an affected child of
      consanguineous parents. Long range and multiplex PCR methods were used to
      characterize this deletion which encompasses exons 3 and 4 and is 1146 base pairs
      long. We propose that Alu element-mediated unequal homologous recombination
      between an Alu-Y in intron 2 and an Alu-Sx in intron 4 is the likely mechanism
      for this deletion, thereby contributing further insight into the molecular
      etiology of this disorder and providing additional evidence of its allelic
      heterogeneity.

PMID- 20138558
TI  - Feline immunodeficiency virus, feline leukemia virus and Bartonella species in
      stray cats on St Kitts, West Indies.
AB  - Stray cats trapped in various areas of Basseterre, the capital of St Kitts in the
      West Indies, were tested for infection with feline immunodeficiency virus (FIV)
      and feline leukemia virus (FeLV) using commercial kits. Of 99 (51 male and 48
      female) cats trapped in 2006/7, 15% (12 males and three females) were positive
      for FIV while none were positive for FeLV. Of 72 (41 males and 31 females) cats
      trapped in 2009, 14% (nine males and one female) were positive for FIV while none
      were positive for FeLV. Polymerase chain reaction analysis revealed DNA of
      Bartonella species in whole blood collected from 60/95 (63%) cats trapped in
      2006/7. Sequencing of the 16S-23S rRNA gene intergenic transcribed spacer (ITS)
      region of a convenience sample of nine amplicons and the 11 isolates made from 43
      blood samples which were cultured using Bartonella alpha Proteobacteria (BAPGM)
      enrichment medium revealed B henselae (14) and B clarridgeiae (six).

PMID- 20138559
TI  - Successful treatment of Bartonella henselae endocarditis in a cat.
AB  - This report describes the clinical presentation, diagnosis and treatment of a cat
      with vegetative valvular endocarditis temporally associated with natural
      infection with Bartonella henselae. Lethargy, abnormal gait and weakness were the
      main clinical signs that resulted in referral for diagnostic evaluation. Using a
      novel and sensitive culture approach, B henselae was isolated from the blood.
      Following antibiotic therapy there was total resolution of clinical signs, the
      heart murmur, the valvular lesion by echocardiography, and no Bartonella species
      was isolated or amplified from a post-treatment blood culture. In conjunction
      with previous case reports, infective endocarditis can be associated with natural
      B henselae infection in cats; however, early diagnosis and treatment may result
      in a better prognosis than previously reported.

PMID- 20138560
TI  - Synthesis of titanium dioxide by ultrasound assisted sol-gel technique: effect of
      amplitude (power density) variation.
AB  - Titanium dioxide was successfully synthesized by utilizing sol-gel technique
      modified by incorporation of ultrasound as a reaction aid. The effect of
      amplitude of irradiation (power input varied from 19.9 to 80.8 W) on % Rutile, %
      yield, % crystallinity, crystallite size and morphological (scanning electron
      microscopy) properties of the obtained nano-TiO(2) was studied. Calcination
      temperatures of all the samples were kept constant at 750 degrees C. With
      increasing ultrasonic irradiation amplitude it is observed that the values of %
      Rutile (after calcination) increased and reached a peak value after which further
      increase in amplitude resulted in a decrease in the % Rutile. A similar trend was
      observed in the case of % crystallinity and % yield of the reaction. On the basis
      of these results an optimum operating ultrasonic irradiation amplitude for the
      reaction has been suitably established.

PMID- 20138561
TI  - The effect of FES of the tibial nerve on physiological activation of leg muscles
      during gait.
AB  - The effects of surface functional electrical stimulation (FES) of the tibial
      nerve of healthy subjects were evaluated. The FES was applied at three different
      times during gait: early, mid and late stances. The purpose of this work is to
      understand the effect of unilateral stimulation on the bilateral activation
      patterns of leg muscles, because FES is used in practice to improve gait, while
      associated neuromuscular change is not often measured. The experimental protocol
      presented here will be transferred to stroke subjects, who could benefit from
      improved push-off during gait. Results show that FES of the tibial nerve changes
      the offset timing of the tibialis anterior muscle on the stimulated side and the
      on- and offset timings of the tibialis anterior muscle of the leg contralateral
      to stimulation. Additionally, activity levels of the semitendinosus ipsilateral
      and tibialis anterior contralateral to the stimulated leg significantly
      decreased, with respect to the non-stimulated condition. For the semitendinosus,
      this was a difference of 6-7microV, with p<0.05. For the tibialis anterior, this
      was a difference of 7-15microV, with a significance of p=0.00, respectively. This
      information is important for future applications of stimulation as it means that
      stimulation not only affects the stimulated muscle but also the physiological
      motor control by the CNS.

PMID- 20138562
TI  - Pain severity and catastrophising modify treatment success in neck pain patients
      in primary care.
AB  - The objective of this study was to evaluate whether clinical factors at baseline
      in patients with non-specific neck pain are related to recovery after treatment
      with manual therapy versus physiotherapy. Participating physiotherapists
      recruited new consulters with complaints of the neck and/or upper extremity. For
      this study we selected patients from this cohort with non-specific neck
      complaints. Participants filled in questionnaires at baseline, 3 and 6 months.
      The main outcome measure was recovery at 6 months follow-up. Possible predictors
      like complaint-specific factors, physical factors, social and psychological
      factors were evaluated for interaction with treatment. Of the 396 participants in
      this study, 97 (24.5%) received manual therapy, all others received
      physiotherapy, consisting of exercises, massage or physical applications. In the
      multivariable model four variables were significantly related to recovery:
      duration of complaint, catastrophising, distress and somatisation. Severity of
      main complaint and catastrophising appeared to show interaction with treatment.
      It appeared that every point increase in severity or catastrophising resulted in
      a lower chance to recover from physiotherapy compared to manual therapy. In
      conclusion, severity of main complaint and catastrophising seem to modify
      treatment success. Increased pain severity or catastrophising at baseline
      increased the chance of treatment success after manual therapy compared to
      physiotherapy.

PMID- 20138563
TI  - Seed desiccation: a bridge between maturation and germination.
AB  - The development of orthodox seeds concludes by a desiccation phase. The dry seeds
      then enter a phase of dormancy, also called the after-ripening phase, and become
      competent for germination. We discuss physiological processes as well as gene
      expression and metabolic programs occurring during the desiccation phase in
      respect to their contribution to the desiccation tolerance, dormancy competence
      and successful germination of the dry seeds. The transition of developing seeds
      from the phase of reserve accumulation to desiccation is associated with distinct
      gene expression and metabolic switches. Interestingly, a significant proportion
      of the gene expression and metabolic signatures of seed desiccation resemble
      those characterizing seed germination, implying that the preparation of the seeds
      for germination begins already during seed desiccation.

PMID- 20138564
TI  - Surgical outcomes and prognostic factors of oral cancer associated with betel
      quid chewing and tobacco smoking in Taiwan.
AB  - Oral squamous cell carcinoma (OSCC) is one of the most common cancers in
      geographic regions where betel quid (BQ) chewing is prevalent; OSCC is an
      extremely malignant neoplasm whose prognostic factors are multiple and complex.
      The purpose of this study was to assess clinicopathological prognostic factors
      and treatment outcomes in 698 consecutive OSCC patients who had undergone surgery
      as the primary treatment in an area with a high prevalence of both betel quid
      chewing and tobacco smoking. The prognostic factors were predicted using Cox's
      proportional-hazards regression model, and the survival rate was calculated using
      Kaplan-Meier analysis. The median followup for all patients was 44 months. The 5
      year cumulative overall, disease-specific, and locoregional control survival
      rates were 61%, 62%, and 46%, respectively. Multivariate analysis showed that the
      lower level of nodal metastasis, advanced stage, tumor thickness >7 mm, and
      treatment failures were independent risk factors of overall survival.
      Furthermore, history of alcohol drinking, lower level of nodal metastasis,
      advanced stage, poor cell differentiation, and treatment failures were
      independent predictors of poor disease-specific survival. However, we did not
      find any significant factor that affected locoregional recurrence. Due to the
      high frequencies of locoregional recurrence and second primary cancer, our
      findings emphasize that aggressive surgical excision, adjuvant treatments
      according to clinicopathological prognostic factors and close surveillance are
      important to the survival of OSCC patients in an area with a high prevalence of
      betel quid chewing and tobacco smoking.

PMID- 20138565
TI  - Plasmablastic lymphoma of the oral cavity: a review.
AB  - Plasmablastic lymphoma (PBL) is a rare AIDS associated non-Hodgkin's lymphoma
      (NHL), with predilection for the mucosa of oral cavity. It usually has a
      plasmablastic morphology, expressing plasma cell-associated antigens with weak or
      no expression of B-cell associated markers. The tumor cells also show monoclonal
      rearrangement of the immunoglobulin heavy chain gene (IgH) and/or clonal
      restriction of Ig light chain (IgL) gene expression in most of the cases. An
      etiological role for EBV seems likely but the association with HHV8 is
      questionable. The treatment guidelines for PBL are not well defined and patients
      have been treated heterogeneously with chemo and/or radiotherapy, although the
      prognosis is poor. The present article discusses the 68 cases reported in English
      medical literature with comprehensive review on PBL involving the oral cavity.

PMID- 20138566
TI  - Multivariate analyses to assess the effect of surgeon volume on survival rate in
      oral cancer: a nationwide population-based study in Taiwan.
AB  - Patients with oral cancer utilize considerable health care resources,
      particularly when wide resection of the tumor and reconstruction with pedicle
      flap/free flap is performed. This study was conducted to explore the relationship
      between survival rates and surgeon volume. A total of 1256 patients who underwent
      resections for oral cancer in 2005 were identified from the Taiwan National
      Health Insurance Research Database. Survival analysis, the Cox proportional
      regression model, and propensity score were used to evaluate the association
      between 3-year survival rates and surgeon caseloads. Oral cancer patients treated
      by high-volume surgeons (caseload 22-117) had better survival rates (hazard ratio
      [HR]=0.656; 95% confidence interval [CI], 0.484-0.89; P=0.007) using the Cox
      proportional regression model after adjusting for patients' comorbid conditions,
      hospital, and surgeon characteristics. When analyzed by propensity score, the
      adjusted 3-year survival rate was 74% for patients treated by high-volume
      surgeons compared to 58% in the low/medium-volume group (P=0.019). We concluded
      that for patients who underwent oral cancer resection and reconstruction, after
      adjusting for differences in the case mix, high-volume surgeons had better 3-year
      survival rates. Treatment strategies adopted by high-volume surgeons should be
      analyzed further and utilized more widely.

PMID- 20138567
TI  - Nuclear Survivin expression is correlated with malignant behaviors of head and
      neck cancer together with Aurora-B.
AB  - Survivin belongs to the inhibitors of apoptosis (IAP) gene family and inhibits
      apoptosis. Besides its role as IAP, Survivin recently appears to function as a
      subunit of the chromosomal passenger complex (CPC) for regulating cell division
      with other CPC proteins including Aurora-B and INCENP. Nuclear Survivin is
      suspected to control cell division, whereas cytoplasmic Survivin is considered
      cytoprotective. Although there are several studies on Survivin expression and its
      function as inhibition of apoptosis, there is no study on Survivin function as a
      CPC and its correlation with other CPC proteins in head and neck squamous cell
      carcinoma (HNSCC). Here, therefore, we examined nuclear Survivin expression and
      its functional correlation with Aurora-B in HNSCC. High expression of Survivin
      was well correlated with Aurora-B expression in nuclear fraction of HNSCC cell
      lines and tissues. Moreover, nuclear Survivin expression was significantly
      correlated with Ki-67 and Aurora-B expression by immunohistochemistry. Notably,
      HNSCC cases with nuclear Survivin and Aurora-B expression exhibited marked
      malignant behaviors. Interestingly, both Survivin and Aurora-B knockdown
      inhibited cell growth and tumorsphere formation. Overall suggest that nuclear
      Survivin may be involved in tumor progression together with Aurora-B, and that
      Survivin and Aurora-B can be useful diagnostic markers and therapeutic targets.

PMID- 20138568
TI  - Arecoline arrests cells at prometaphase by deregulating mitotic spindle assembly
      and spindle assembly checkpoint: implication for carcinogenesis.
AB  - One apparent feature of cancerous cells is genomic instability, which may include
      various types of chromosomal aberrations, such as translocation, aneuploidy, and
      the presence of micronuclei inside the cells. Mutagenic factors that promote the
      emergence of genomic instability are recognized as risk factors for the
      development of human malignancies. In Asia, betel quid (BQ) chewing is one of
      such risk factors for oral cancer. Areca nut is an essential constitute of BQ and
      is declared as a group I carcinogen by the International Agency for Research on
      Cancer. However, the molecular and cellular mechanisms regarding the
      carcinogenicity of areca nut are not fully explored. Here we reported that
      arecoline, a major alkaloid of areca nut, could arrest cells at prometaphase with
      large amounts of misaligned chromosomes. This prometaphase arrest was evidenced
      by condensed chromosome pattern, increased histone H3 phosphorylation, and
      accumulation of mitotic proteins, including aurora A and cyclin B(1). To
      investigate the molecular mechanisms accounting for arecoline-induced
      prometaphase arrest, we found that arecoline could stabilize mitotic spindle
      assembly, which led to distorted organization of mitotic spindles, misalignment
      of chromosomes, and up-regulation of spindle assembly checkpoint (SAC) genes. The
      SAC proteins BubR1 and Mps1 were differentially modified between the cells
      treated with arecoline and nocodazole. This together with aurora A overexpression
      suggested that SAC might be partly suppressed by arecoline. As a result, the
      arecoline-exposed cells might produce progeny that contained various chromosomal
      aberrations and exhibited genomic instability.

PMID- 20138569
TI  - Potential biomarkers in saliva for oral squamous cell carcinoma.
AB  - Sensitive and reliable early diagnostic markers for oral squamous cell carcinoma
      (OSCC) remain unavailable. Early identification of recurrence for OSCC is also a
      challenge. Unlike the other deep cancers, OSCC is located in oral cavity. The
      DNA, RNA, and protein derived from the living cancer cells and inflammatory cells
      then can be conveniently obtained from saliva. High-throughput genomic and
      proteomic approaches have been carried out to identify the potential biomarkers
      in body fluids such as saliva and blood for diagnosis and prognosis of OSCC. This
      article reviewed the recently identified biomarkers from saliva for OSCC. In
      addition, the biomarkers which have been correlated with OSCC tumor malignancy by
      molecular pathology analysis are also described. Finally, the potential
      biomarkers that have been demonstrated to associate with the malignant OSCC may
      be used for salivary screening for high-risk patients are suggested. This article
      may help to identify the potential biomarkers for screening and the molecular
      pathology analysis for high-risk patients of OSCC. Effective screening to
      identify high-risk patients can allow the clinician to provide the appropriate
      treatment without delay and to reduce the recurrence of OSCC.

PMID- 20138570
TI  - Scintigraphic evaluation of mandibular bone turnover in patients with solid
      tumors receiving zoledronic acid.
AB  - Bisphosphonates (BP) have been associated with the occurrence of osteonecrosis of
      the jaw (ONJ), possibly by causing an excessive bone turnover inhibition.
      However, little in vivo evidence exists to support this theory. The (99m)Tc
      medronate scintigrams of patients with skeletal metastases and BP use (n=40) were
      individually matched with cancer patients without BP exposure (n=40) and controls
      with neither malignancy nor BP use (n=40). Patients with established ONJ or
      intense focal abnormalities in the studied regions were excluded. Mandibular
      (MBT) bone turnover was quantified relative to the femur by defining regions-of
      interest with correction for background activity. The patients with BP exposure
      (34 female, 6 male) had a median age of 63 years (range 25-81) and received a
      median number of 11 zoledronic acid administrations (range 1-44). Most patients
      suffered from breast cancer (n=30). The mean ratio of the MBT in cancer patients
      with BP use over non-users was 0.88 (95% CI 0.80-0.96; p=0.003), and 0.83 (95% CI
      0.73-0.94; p=0.001) when BP using oncological patients were compared with
      controls without malignancy or BP use. The ratio of MBT's between BP naive
      patients was 0.95 (95% CI 0.83-1.07; p=0.8). No dose-response effect between the
      number of BP administrations and MBT could be demonstrated (r=0.02; p=0.9). These
      findings suggest that, relative to the femur, BP exert a stronger effect on
      mandibular bone turnover, which strengthens the hypothesis that the inhibition of
      bone turnover may be important in the pathophysiology of ONJ.

PMID- 20138571
TI  - Estimation of the ground and the first excited singlet-state dipole moments of
      1,4-disubstituted anthraquinone dyes by the solvatochromic method.
AB  - The both, ground-state (mu(g)) and the excited-state (mu(e)) dipole moments of
      three 1,4-disubstituted anthraquinones, namely 1,4-diaminoanthracene-9,10-dione
      (1,4-DAAQ), 1-amino-4-hydroxyanthracene-9,10-dione (1,4-AHAQ), and 1,4
      dihydroxyanthracene-9,10-dione (1,4-DHAQ) were estimated in binary solvent
      mixtures (methylcyclohexane-ethyl acetate and ethyl acetate-acetonitrile). The
      dipole moments (mu(g) and mu(e)) were estimated from Lippert-Mataga, Bakhshiev,
      Kawski-Chamma-Viallet, McRae, and Suppan equations by using the variation of
      Stokes shift with the solvent's relative permittivity and refractive index. The
      ground-state dipole moments were also calculated theoretically by Gaussian 03
      software using B3LYP/6-31 G* level of theory. Further, the change in dipole
      moment values Deltamu were also calculated by using the variation of Stokes shift
      with the molecular-microscopic empirical solvent polarity parameter (E(T)(N)).
      The excited-state dipole moments observed are larger than their ground-state
      counterparts, indicating a substantial redistribution of the pi-electron
      densities in a more polar excited state for all the molecules investigated.

PMID- 20138572
TI  - Fourier transformed infrared spectral investigations of molecular interactions in
      propionic acid-2-propanol binary system.
AB  - FTIR spectra of propionic acid (PA), 2-propanol (PROH) and its binary mixtures
      with varying molefraction of the PA were recorded in the region 500-3500 cm(-1),
      to investigate the formation of hydrogen bonded complexes in a mixed system. The
      observed features in nu(CO), nu(CO) and delta(COH) of PA, nu(CO) of PROH and
      delta(COH) of PA+PROH have been explained in terms of the hydrogen bonding
      interactions between PROH and PA and dipole-dipole interaction. The dipole moment
      derivative for the above mentioned vibrational modes have also been predicted
      from the integrated absorbance. The intrinsic linewidth for the vibrational modes
      nu(CO) and delta(COH) of PA has been elucidated using Bondarev and Mardaeva
      model.

PMID- 20138573
TI  - Studies of the spin-Hamiltonian parameters and the Jahn-Teller distortions for
      tetragonal Cu(H(2)O)(6)(2+) clusters in trigonal A(2)Mg(3)(NO(3))(12).24H(2)O
      (A=La, Bi) crystals.
AB  - The anisotropic and isotropic spin-Hamiltonian parameters (g factors and
      hyperfine structure constants) of tetragonal Cu(H(2)O)(6)(2+) clusters due,
      respectively, to the static and dynamic Jahn-Teller effects for Cu(2+) in
      trigonal A(2)Mg(3)(NO(3))(12).24H(2)O (A=La, Bi) crystals are calculated from the
      high-order perturbation formulas based on the cluster approach. In the approach,
      the admixture between the d orbitals of 3d(n) ion and the p orbitals of ligand
      ion via covalence effect is considered. All of the calculated results are in
      agreement with the experimental values. The tetragonal elongations (characterized
      by DeltaR=R(parallel)-R( perpendicular)) of Cu(H(2)O)(6)(2+) cluster due to the
      Jahn-Teller effect in A(2)Mg(3)(NO(3))(12).24H(2)O crystals are acquired from the
      calculations. The results are discussed.

PMID- 20138574
TI  - Substitution reactions of thorium(IV) acetate to synthesize nano-sized
      carboxylate complexes.
AB  - Some mixed-ligand thorium(IV) complexes with the general formula [Th(OOCCH(3))(4
      n)L(n)] (L=anions of myristic, palmitic or stearic acid and n=1-4) have been
      synthesized by the stepwise substitution of acetate ions of thorium(IV) acetate
      with straight chain carboxylic acids in toluene under reflux. The complexes were
      characterized by elemental analyses, spectral (electronic, infrared, NMR and
      powder XRD) studies, electrical conductance and magnetic susceptibility
      measurements. Doubly and triply bridged coordination modes of the ligands were
      established by their infrared spectra and nano-size of the complexes by powder
      XRD. Room temperature magnetic susceptibility measurements revealed diamagnetic
      nature of the complexes. Electronic absorption spectra of the complexes showed pi
      ->pi*, n-->pi* and charge transfer transitions. Molar conductance values
      indicated the complex to be non-electrolytes. These are a new type of mixed
      ligand thorium(IV) complexes for which a nano-sized, oxygen bridged polymeric
      structure has been established on the basis of physico-chemical studies.

PMID- 20138575
TI  - Synthesis and magnetic behaviour of Mn:ZnO nanocrystalline powders.
AB  - This paper reports on the magnetic properties of Mn:ZnO nanoparticles. XRD
      profiles have shown that the undertaken materials are in wurtzite structures. The
      crystallite size of the sample has been examined using TEM for one sample. In
      order to verify the lattice site occupancy and also valence state of the
      manganese ion, EPR spectral measurements have also been carried out for these
      samples. The magnetic properties of the samples have been investigated on a
      Vibrating Sample Magnetometer (VSM).

PMID- 20138576
TI  - Spectrophotometric and spectroscopic studies of charge transfer complexes of p
      toluidine as an electron donor with picric acid as an electron acceptor in
      different solvents.
AB  - The charge transfer complexes of the donor p-toluidine with pi-acceptor picric
      acid have been studied spectrophotometrically in various solvents such as carbon
      tetrachloride, chloroform, dichloromethane acetone, ethanol, and methanol at room
      temperature using absorption spectrophotometer. The results indicate that
      formation of CTC in non-polar solvent is high. The stoichiometry of the complex
      was found to be 1:1 ratio by straight-line method between donor and acceptor with
      maximum absorption bands. The data are discussed in terms of formation constant
      (K(CT)), molar extinction coefficient (epsilon(CT)), standard free energy
      (DeltaG(o)), oscillator strength (f), transition dipole moment (mu(EN)),
      resonance energy (R(N)) and ionization potential (I(D)). The results indicate
      that the formation constant (K(CT)) for the complex was shown to be dependent
      upon the nature of electron acceptor, donor and polarity of solvents that were
      used.

PMID- 20138577
TI  - Personal digital assistant with a barcode reader--a medical decision support
      system for nurses in home care.
AB  - INTRODUCTION: Inappropriate medication among elderly people increases the risk of
      adverse drug-drug interactions, drug-related falls and hospital admissions. In
      order to prevent these effects it is necessary to obtain a profile of the
      patients' medication. A personal digital assistant (PDA) can be used as a medical
      decision support system (MDSS) to obtain a profile of the patients' medication
      and to check for inappropriate drugs and drug combinations, and to reduce
      medication errors. AIM: The aim of the present study was to evaluate nurses'
      experiences of using a MDSS in a PDA with a barcode reader, in order to obtain
      profiles of the patients' medication, regarding drug-drug interactions,
      therapeutic duplications, and warnings for drugs unsuitable for elderly in home
      care. METHODS: The LIFe-reader is a MDSS in a PDA with a barcode reader. By
      scanning the drug packages in the patients' home, the LIFe-reader obtained
      profiles of the patients' medication and checked for drug-drug interactions,
      therapeutic duplications and warnings for drugs unsuitable for elderly people.
      The LIFe-reader also contained, e.g. drug information and medical reference
      works. Nurses (n=15) used the LIFe-reader for five weeks during their nursing
      home care practice assignment. The nurses answered questionnaires about the
      content and functions of the LIFe-reader before, during and after the nursing
      home care practice assignment, and were interviewed in focus groups. Descriptive
      statistics were used and content analysis was applied for qualitative data.
      RESULTS: By using the LIFe-reader, the majority of the nurses found it easy to
      obtain profiles of the patients' medication and check for drug-drug interactions,
      therapeutic duplications and warnings for drugs unsuitable for elderly people.
      Most nurses regarded the LIFe-reader to reduce drug-related risks of falling, and
      some thought it could reduce the drug-related admissions to hospitals. The
      scanning function was described as easy and time saving, although not always
      possible to use. The LIFe-reader was regarded as a useful and user-friendly MDSS,
      but more content and functions were requested. CONCLUSIONS: We found that the
      LIFe-reader has the potential to be a useful and user-friendly MDSS for nurses in
      home care when obtaining profiles of the patients' medication regarding drug-drug
      interactions, therapeutic duplications and warnings for drugs unsuitable for
      elderly. A regular scanning of the patients' drugs in their home might support
      nurses and general practitioners (GPs) in reducing the inappropriate use of
      drugs. If the LIFe-reader should be used in a larger scale among nurses, more
      content and functions are necessary.

PMID- 20138578
TI  - Cross-cultural differences in infant and toddler sleep.
AB  - BACKGROUND: To characterize cross-cultural sleep patterns and sleep problems in a
      large sample of children ages birth to 36 months in multiple predominantly-Asian
      (P-A) and predominantly-Caucasian (P-C) countries. METHODS: Parents of 29,287
      infants and toddlers (predominantly-Asian countries/regions: China, Hong Kong,
      India, Indonesia, Korea, Japan, Malaysia, Philippines, Singapore, Taiwan,
      Thailand, Vietnam; predominantly-Caucasian countries: Australia, Canada, New
      Zealand, United Kingdom, United States) completed an internet-based expanded
      version of the Brief Infant Sleep Questionnaire. RESULTS: Overall, children from
      P-A countries had significantly later bedtimes, shorter total sleep times,
      increased parental perception of sleep problems, and were more likely to both bed
      share and room-share than children from P-C countries, p<.001. Bedtimes ranged
      from 19:27 (New Zealand) to 22:17 (Hong Kong) and total sleep time from 11.6
      (Japan) to 13.3 (New Zealand) hours, p<.0001. There were limited differences in
      daytime sleep. Bed-sharing with parents ranged from 5.8% in New Zealand to 83.2%
      in Vietnam. There was also a wide range in the percentage of parents who
      perceived that their child had a sleep problem (11% in Thailand to 76% in China).
      CONCLUSIONS: Overall, children from predominantly-Asian countries had
      significantly later bedtimes, shorter total sleep times, increased parental
      perception of sleep problems, and were more likely to room-share than children
      from predominantly-Caucasian countries/regions. These results indicate
      substantial differences in sleep patterns in young children across culturally
      diverse countries/regions. Further studies are needed to understand the basis for
      and impact of these interesting differences.

PMID- 20138579
TI  - Sleep and body mass index in depressed children and healthy controls.
AB  - OBJECTIVE: Higher body mass index (BMI) has been associated with more sleep
      disturbance and depressive symptoms, but the combined effects of depression and
      BMI on sleep have not been studied in children. This study evaluated the
      relationship between BMI and polysomnography in children with major depressive
      disorder (MDD), compared to healthy controls (HCs). METHOD: The sample of 104
      subjects included 72 children, 8-17 years old, with MDD and 32 similarly aged HCs
      with no personal or family history of psychopathology. BMI was adjusted using the
      CDC formula for percentiles by age. Subjects were categorized as (1) normal
      weight (5-84th percentile) or (2) high weight, which included at risk of
      overweight and overweight (> or = 85th percentile). All analyses were adjusted
      for sex and Tanner maturational stage scores. RESULTS: In the MDD group only,
      higher BMI was significantly correlated with decreased sleep efficiency,
      decreased percentage of rapid eye movement sleep (REM%), and higher percentage of
      time spent awake and moving (TSPAM). In the HC group only, higher BMI correlated
      with higher total sleep time. Multivariate analyses revealed significant
      interactions between the BMI and diagnostic groups for several REM sleep
      parameters, such that high-weight children from the HC and MDD groups had
      increases and decreases in REM sleep, respectively. TSPAM increased in the high
      weight MDD group, but decreased in the high-weight HC group. CONCLUSIONS:
      Although limited by small sample size, these findings suggest that children and
      adolescents with MDD and a high BMI have more fragmented sleep than other
      children. The increased REM sleep patterns observed with MDD in this and other
      studies normalized in high-weight children with MDD. Prevention and treatment
      strategies should target both sleep and weight as factors that can potentially
      influence the development and course of MDD.

PMID- 20138580
TI  - Uridine insertion/deletion RNA editing in Trypanosomatids: specific stimulation
      in vitro of Leishmania tarentolae REL1 RNA ligase activity by the MP63 zinc
      finger protein.
AB  - U-insertion/deletion RNA editing of mitochondrial mRNAs in trypanosome
      mitochondria is mediated by a core complex (RECC) containing around 16-20
      proteins which is linked to several other multiprotein complexes by RNA. There
      are two known subcomplexes in the RECC: the REL1 subcomplex which contains the
      REL1 RNA ligase, the MP63 zinc finger-containing protein and the REX2 U-specific
      3'-5' exonuclease; and the REL2 subcomplex which contains the REL2 RNA ligase,
      the RET2 3' TUTase and the MP81 zinc finger-containing protein. In this study we
      have affinity isolated recombinant TAP-tagged Leishmania major RET2 and
      Leishmania tarentolae MP63, REL1 and REL2 proteins after expression in
      baculovirus-infected insect cells. Recombinant MP63 protein was found to
      stimulate several in vitro activities of recombinant REL1; these activities
      include autoadenylation, bridged ligation and even pre-cleaved gRNA-mediated U
      insertion editing with RET2 which is in the REL2 subcomplex. There was no effect
      of recombinant MP63 on similar REL2 ligation activities. The specificity for REL1
      is consistent with MP63 being a component of the REL1 subcomplex. These results
      suggest that in vivo the interaction of MP63 with REL1 may play a role in
      regulating the overall activity of RNA editing.

PMID- 20138581
TI  - Recent advances and future trends in multimodality cardiac imaging.
AB  - The cardiovascular imaging field has experienced marked growth and technical
      advancement in the past several decades. In the future, multimodality imaging
      will provide enhanced characterisation of disease states. Myocardial perfusion
      imaging will become more quantitative, permitting measurement of absolute blood
      flow and coronary flow reserves during stress states. A greater use of positron
      emission tomography (PET) can be expected for both assessing blood flow
      quantitatively and molecular imaging of atherosclerotic plaques and myocardial
      disease states. SPECT and PET imaging of myocardial metabolism and cardiac
      neuronal imaging have already shown great promise for identifying high-risk
      patients with coronary heart disease and nonischaemic cardiomyopathy. Further
      progress will occur in computed tomography imaging of the heart and coronary
      arteries and cardiac magnetic resonance imaging including quantitative estimates
      of coronary blood flow, coronary and peripheral vessel plaque characterisation,
      and detection of myocardial cellular dysfunction. Fusion imaging, in which two
      disparate image data sets are merged into one functional image, will become
      commonplace. Major breakthroughs in CV imaging will depend on discoveries in
      basic research, further refinement of instrumentation and software for image
      processing and analysis, and outcomes research demonstrating the worth of imaging
      technologies in reducing cardiovascular death and morbidity.

PMID- 20138582
TI  - Anticancer genes: inducers of tumour-specific cell death signalling.
AB  - Recent studies have revealed a new class of genes encoding proteins with specific
      anticancer activity. Upon ectopic expression, these factors cause cell death
      specifically in tumour cells by apoptosis, autophagy or mitotic catastrophe, yet
      normal cells are spared. Some of these genes or their encoded proteins are in
      clinical development and show promising results, and their signalling pathways
      are currently under intense investigation. Defining these genes as anticancer
      genes, we review what is known about their functions, the specific cell death
      signals they induce and the status of cancer therapy approaches that emulate
      their function. Systematic screening for such anticancer genes might lead to the
      identification of a repertoire of signalling pathways directed against cellular
      alterations that are specific for tumour cells.

PMID- 20138583
TI  - Motivation and its relationship to adherence to self-monitoring and weight loss
      in a 16-week Internet behavioral weight loss intervention.
AB  - OBJECTIVE: To examine changes in motivation and the relationship of motivation to
      adherence to self-monitoring and weight loss in a 16-week Internet behavioral
      weight-loss intervention. DESIGN: Two-group randomized design. SETTING: This
      study was conducted over the Internet. PARTICIPANTS: Sixty-six women, ages 22-65,
      with a body mass index (BMI) between 25 and 40, and with a home computer with
      Internet access, participated. INTERVENTION: These data are from an Internet
      behavioral weight-loss program in which all participants received a face-to-face
      initial session followed by the 16-week Internet program. MAIN OUTCOME MEASURES:
      Adherence to self-monitoring and weight loss were the main outcome measures.
      ANALYSIS: Linear regression and mediation analysis using the Baron and Kenny
      method were conducted. RESULTS: Autonomous motivation increased initially and
      remained high for those who ultimately achieved a 5% weight loss, but declined
      over time for participants who did not achieve a 5% weight loss. Autonomous
      motivation at 4 weeks was a predictor of adherence to self-monitoring and 16-week
      weight loss. Adherence mediated the relationship between autonomous motivation
      and weight loss. CONCLUSIONS AND IMPLICATIONS: These results suggest that
      autonomous motivation may be a promising intervention target for promoting
      program procedure adherence and weight loss.

PMID- 20138584
TI  - Behavioral change theories can inform the prediction of young adults' adoption of
      a plant-based diet.
AB  - OBJECTIVE: Drawing on the Theory of Planned Behavior (TPB) and the
      Transtheoretical Model (TTM), this study (1) examines links between stages of
      change for following a plant-based diet (PBD) and consuming more fruits and
      vegetables (FV); (2) tests an integrated theoretical model predicting intention
      to follow a PBD; and (3) identifies associated salient beliefs. DESIGN: Cross
      sectional. SETTING: Large public university in the northeastern United States.
      PARTICIPANTS: 204 college students. MAIN OUTCOME MEASURES: TPB and TTM constructs
      were assessed using validated scales. Outcome, normative, and control beliefs
      were measured using open-ended questions. ANALYSIS: The overlap between stages of
      change for FV consumption and adopting a PBD was assessed using Spearman rank
      correlation analysis and cross-tab comparisons. The proposed model predicting
      adoption of a PBD was tested using structural equation modeling (SEM). Salient
      beliefs were coded using automatic response coding software. RESULTS: No
      association was found between stages of change for FV consumption and following a
      PBD. Results from SEM analyses provided support for the proposed model predicting
      intention to follow a PBD. Gender differences in salient beliefs for following a
      PBD were found. CONCLUSIONS AND IMPLICATIONS: Results demonstrate the potential
      for effective theory-driven and stage-tailored public health interventions to
      promote PBDs.

PMID- 20138585
TI  - C-reactive protein in myocardial infarction binds to circulating microparticles
      but is not associated with complement activation.
AB  - BACKGROUND: C-reactive protein (CRP) is elevated in patients with acute
      myocardial infarction (AMI). When CRP binds to membrane phospholipids or Fc
      receptors, it activates the complement system. Recent studies show that CRP can
      be exposed on cell-derived microparticles (MP) and is associated complement
      activation. OBJECTIVES: We studied complement activation on circulating MP in AMI
      patients and healthy controls. METHODS: MP were isolated from plasma of AMI
      patients (n=21) and sex- and age-matched healthy individuals (n=10), and analyzed
      by flow cytometry for bound complement components (C1q, C4, C3) and complement
      inhibitor and activator molecules (C4bp, CRP, serum amyloid P component,
      immunoglobulins IgM and IgG). Concurrently, the levels of fluid phase complement
      activation products and inhibitor and activator molecules were determined.
      RESULTS: Fluid phase CRP, MP with bound CRP (CRP + MP), and C3 activation
      products were elevated in AMI patients compared to controls (P=0.032, P=0.031 and
      P=0.023, respectively), and fluid phase CRP correlated with CRP+ MP (r=0.84,
      P<0.001). Although CRP+ MP were elevated, they were not associated with C1q+ MP
      (r=0.32, P=0.174). In contrast, IgG+ MP were associated with C1q+ MP (r=0.73,
      P<0.001), C4+ MP and C3+ MP (r=0.78 and r=0.87, respectively; both P<0.001), and
      C4bp (r=0.63, P=0.004). In healthy individuals, CRP+ MP were strongly associated
      with C1q+ MP (r=0.82, P=0.007), which in turn were associated with C4+ MP and C3+
      MP (r=0.68, P=0.032 and r=0.68, P=0.031, respectively). CONCLUSIONS: Despite CRP
      associated complement activation on the surface of MP in healthy individuals and
      a strong correlation between MP-bound CRP and fluid phase CRP in AMI patients,
      the MP-associated complement activation is IgG- but not CRP-dependent in AMI
      patients.

PMID- 20138586
TI  - Inhibition of B cell-mediated antigen presentation by intravenous immunoglobulins
      (IVIg).
AB  - Previous work from our laboratory revealed that IVIg interacted with
      intracellular proteins involved in antigen presentation in B cells, suggesting
      that IVIg might interfere with the process of antigen presentation in these
      cells. In the present work, we used an in vitro assay with ovalbumin as model
      antigen and showed that IVIg inhibited both BCR-dependent and BCR-independent
      antigen presentation. The inhibition could not be explained by a modulation of
      expression of MHC II molecules expressed on B cells and was shown to occur in an
      FcgammaRIIb-independent manner, suggesting that the events responsible for the
      inhibitory effect occur at the intracellular level. This was supported by the
      observation of a direct correlation between the level of spontaneous
      internalization of two different proteins (IVIg and HSA) and their inhibitory
      potential. The inhibition of B cell-mediated antigen presentation reported here
      may help explain some of the anti-inflammatory effects of IVIg observed in
      treated patients, such as a decrease in autoantibody production.

PMID- 20138587
TI  - Suicidal thoughts in epilepsy: a community-based study in Brazil.
AB  - Epilepsy has been associated with increased risk of suicide; however, few studies
      have examined the relationship between epilepsy and suicidal behavior. The aims
      of this study were to evaluate the frequency of suicidal behavior in people with
      epilepsy and to identify characteristics that are associated with suicidal
      ideation in epilepsy. Of 171 people with epilepsy identified in a previous
      survey, 139 were included. A structured interview was conducted, and a second
      psychiatric evaluation was scheduled for those who agreed. The frequencies of
      suicidal thoughts, plans, and attempts during lifetime were 36.7, 18.2, and
      12.1%, respectively. The following conditions were strongly associated with
      suicidal thoughts: anxiety (OR=3.3, 95% CI=1.4-7.5, P=0.001), depression (OR=4.8,
      95% CI=1.9-12.5, P=0.001), and two or more standardized psychiatric diagnoses
      (OR=21.6, 95% CI=4.4-105.9, P<0.0001). Although specific characteristics of
      epilepsy were found to be related to suicidal thoughts, psychiatric diseases also
      play an essential role.

PMID- 20138588
TI  - Handedness, alexithymia, and focus laterality as risk factors for psychiatric
      comorbidity in patients with epilepsy.
AB  - The aim of the current study was to evaluate the effect of seizure
      lateralization, handedness, and alexithymia on psychopathology in patients with
      temporal lobe epilepsy. One hundred five patients were included in the study. The
      Hopkins Symptom Checklist--90 (SCL-90) and Toronto Alexithymia Scale (TAS-26)
      were used for psychopathological assessment of patients. Handedness was evaluated
      using Annett's scale. Among the patients studied were 74 right-handers and 31
      left-handers, and 25 alexithymic and 80 nonalexithymic persons. Left-sided foci
      were observed in 52, and right-sided foci in 53 persons. MANOVA was used for
      analysis of the interrelationship between nominal fixed factors (handedness,
      alexithymia, and focus laterality) and the dependent variables SCL-90, Hamilton
      Rating Scale for Depression, and Hamilton Rating Scale for Anxiety. MANOVA
      revealed that alexithymia exerts maximal effect on psychopathological variables,
      and maximal values of SCL-90 constructs were observed for persons with
      alexithymia/left-handedness and alexithymia/right-sided seizure focus
      combinations.

PMID- 20138589
TI  - A new homozygous mutation of the KCNQ1 gene associated with both Romano-Ward and
      incomplete Jervell Lange-Nielsen syndromes in two sisters.

PMID- 20138590
TI  - Warm SPA-induced hyperthermia confers protection to rats against airway
      inflammation evoked by capsaicin and substance P.
AB  - Solus par aqua (SPA) is a traditional health care therapy. Warm SPA may enhance
      immunity and cellular defense to protect body against diseases. The present study
      investigated whether the warm SPA could confer protection to neurogenic
      inflammation in rats. The rats were immersed in water where the body core
      temperatures were maintained at hyperthermia (41.5 degrees C) or normothermia (37
      degrees C) for a period of 15min. After SPA for 1 or 6 days, neurogenic
      inflammation was induced by intravenous injection of capsaicin (90microg/kg) or
      substance P (SP; 3microg/kg). The plasma leakage and arterial pressures in rats
      after neurogenic inflammation were monitored. The extent of capsaicin- or SP
      induced plasma leakage and hypotension was significantly attenuated in rats on
      day 1 after SPA hyperthermia. However, such resistance to neurogenic inflammation
      was not found on day 6 after hyperthermia. Western blotting analysis showed that
      the expression of heat shock protein 72 (HSP 72) in the trachea on days 1 and 2
      after hyperthermia was 9.61-fold and 6.66-fold, respectively, of that in
      normothermia. Afterwards, the hyperthermia-induced HSP 72 upregulation gradually
      declined in a time-dependent manner. Thus, SPA hyperthermia may protect rats
      against neurogenic inflammation through modulation of HSP expression.

PMID- 20138591
TI  - Functional residues on the surface of the N-terminal domain of yeast Pms1.
AB  - Saccharomyces cerevisiae MutLalpha is a heterodimer of Mlh1 and Pms1 that
      participates in DNA mismatch repair (MMR). Both proteins have weakly conserved C
      terminal regions (CTDs), with the CTD of Pms1 harboring an essential endonuclease
      activity. These proteins also have conserved N-terminal domains (NTDs) that bind
      and hydrolyze ATP and bind to DNA. To better understand Pms1 functions and
      potential interactions with DNA and/or other proteins, we solved the 2.5A crystal
      structure of yeast Pms1 (yPms1) NTD. The structure is similar to the homologous
      NTDs of Escherichia coli MutL and human PMS2, including the site involved in ATP
      binding and hydrolysis. The structure reveals a number of conserved, positively
      charged surface residues that do not interact with other residues in the NTD and
      are therefore candidates for interactions with DNA, with the CTD and/or with
      other proteins. When these were replaced with glutamate, several replacements
      resulted in yeast strains with elevated mutation rates. Two replacements also
      resulted in NTDs with decreased DNA binding affinity in vitro, suggesting that
      these residues contribute to DNA binding that is important for mismatch repair.
      Elevated mutation rates also resulted from surface residue replacements that did
      not affect DNA binding, suggesting that these conserved residues serve other
      functions, possibly involving interactions with other MMR proteins.

PMID- 20138592
TI  - Incorporating genetic potential when evaluating stature in children with cystic
      fibrosis.
AB  - OBJECTIVE: The 2002 Cystic Fibrosis Foundation (CFF) practice guidelines
      recommend adjusting for genetic potential when evaluating height status in
      children with CF. However, there is paucity of data to support this
      recommendation. We compared three methods of classifying short stature:
      unadjusted height percentile <10th, Himes adjusted height percentile <10th, and
      unadjusted height below the CFF target height lower bound. PATIENTS AND METHODS:
      Data from 3306 children with parental heights documented in the 1986-2005 CFF
      Patient Registry were analyzed. RESULTS: Mean height percentile of CF children
      (33rd) was lower than their parents' (mothers' 53rd, fathers' 57th), and 80% of
      CF children were below the average of their parental height percentiles. In
      children with short parents, Himes adjusted height percentile was significantly
      higher than unadjusted height percentile (27th vs. 8th), whereas the opposite was
      found in children with tall parents (Himes adjusted at 18th vs. unadjusted at
      49th). Consequently, the prevalence of short stature decreased from 52% to 22% in
      children with short parents and increased from 8% to 34% in children with tall
      parents after Himes adjustment. In children with discrepant classification on
      short stature before and after Himes adjustment, percent predicted forced
      expiratory volume in one second was negatively associated with unadjusted height
      percentile but positively associated with Himes adjusted height percentile. In
      children with short parents, the CFF method underestimated the prevalence of
      short stature (9%) compared to the Himes method (22%). CONCLUSION: Without
      adjustment of genetic potential, the prevalence of short stature is
      underestimated and the association between height and lung function is biased.

PMID- 20138593
TI  - The release kinetics of drug eluting stents containing sirolimus as coated drug:
      role of release media.
AB  - Prior understanding on the in vitro release profile of the drug from drug eluting
      devices such as stent (DES) is crucial in designing and optimizing the drug
      embedded coating or matrices. In fact, assessing in vitro release profile is a
      mandatory requirement prior to the clinical evaluation of DES. The in vitro
      release is also employed to estimate parameters such as T1/2. The release profile
      largely depends on the release medium selected for the studies. Normally PBS with
      a pH of 7.4 is used for assessing the release kinetics of the drug. Often drug
      undergoes irreversible changes such as hydrolysis in PBS leading to erroneous
      assessment of the release profile. This is particularly true in the case of
      sirolimus, one of the widely used drugs in various applications. We studied the
      influence of various media on the release profile of sirolimus from DES. The data
      generated suggested that a release medium consisting of 9:1 (v/v) of normal
      saline and isopropanol is a most suitable one for assessing in vitro the release
      kinetics of sirolimus from DES.

PMID- 20138594
TI  - Liquid chromatography-tandem mass spectrometry method for determination of the
      pyridinium aldoxime 4-PAO in brain, liver, lung, and kidney.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was validated
      and applied to the in vitro determination of 4-[(hydroxyimino)methyl]-1
      octylpyridinium cation (4-PAO), which can penetrate the blood-brain barrier and
      reactivate acetylcholinesterase (AChE) inhibited by alkylphosphonate in the
      brain, liver, lung, and kidney. The limit of detection (LOD) was 0.235 microg
      cation/g wet weight, and the quantification range and linearity of the
      calibration curve extended over a range of 0.470-941 microg cation/g wet weight.
      For the proof of applicability, when 4-PAO was administrated intravenously via
      the rat tail vein at 10% LD(50), we were able to quantify the 4-PAO concentration
      in the tissues: brain 7.60+/-1.32 microg cation/g wet weight (mean+/-SD, n=5),
      liver 26.8+/-2.82 microg cation/g, lung 76.4+/-24.9mugcation/g, and kidney 638+/
      266 microg cation/g. In addition, the methods for 4-[(hydroxyimino)methyl]-1
      decylpyridinium bromide (4-PAD) and 4-[(hydroxyimino)methyl]-1-(2-phenylethyl)
      pyridinium bromide (4-PAPE) were partly validated referring to the findings of
      the 4-PAO full validation. Thus, the LC-MS/MS method described in this study can
      be useful for quantification of pyridinium aldoxime methiodide (PAM)-type oximes
      in biological samples.

PMID- 20138595
TI  - Quantitation of polar analytes using column-switching: application to oxycodone
      and three metabolites in human plasma.
AB  - We present herein a sensitive and selective assay for the determination of
      oxycodone and its main metabolites, oxymorphone, noroxycodone and noroxymorphone
      in human plasma, using column-switching and liquid chromatography coupled to
      tandem mass spectrometry (LC-MS/MS). Sample preparation comprised protein
      precipitation with perchloric acid. After neutralization, the supernatant was
      injected without any evaporation step onto a polymeric, pH-resistant cartridge
      (HySphere Resin GP 10-12 microm) for sample clean-up (Prospekt II). The latter
      operation was achieved by using alkaline conditions to ensure retention of
      analytes and methanol for matrix interference removal. More than two hundred
      plasma samples could be analyzed with a single cartridge. Analytes were desorbed
      in the backflush mode and were separated on a conventional reversed phase column
      (XTerra MS 4.6 x 50 mm, 3.5 microm), using an acidic mobile phase (i.e.
      containing 0.1% of formic acid). Mass spectrometric detection was achieved with a
      4000 Q TRAP equipped with an atmospheric pressure chemical ionization (APCI)
      source, in positive ionization mode, operated in the selected reaction monitoring
      mode (SRM). Starting from a plasma volume of 250 microl, quantification ranges
      were 25-10,000 pg/ml for OXM and NOXM and 50-10,000 pg/ml for OXC and NOXC.
      Accuracy was found to be within 98% and 108% and precision better than 7%.
      Replicate determination of incurred or study samples ensured the method to be
      reproducible and usable for clinical studies.

PMID- 20138596
TI  - [Routine performance of thyroid ultrasound and fine-needle aspiration biopsy in
      the setting of a high-resolution endocrinology practice].
AB  - INTRODUCTION: Fine-needle aspiration biopsy (FNAB) is considered the reference
      diagnostic procedure for thyroid nodules. MATERIALS AND METHODS: Routine
      performance of thyroid ultrasound and ultrasound-guided FNAB by endocrinologists
      allows a more efficient approach in the setting of a high-resolution practice,
      thus reducing costs and the time elapsed until diagnosis. RESULTS: We present our
      initial results of this procedure 2 years after its introduction, with a total of
      286 biopsies performed. After a progressive learning curve over time and
      according to the endocrinologists' previous experience, 72.72% samples were
      considered satisfactory for diagnosis. Greater difficulty was observed in
      obtaining optimal cytological specimens in smaller nodules. In conclusion, we
      have successfully incorporated thyroid ultrasound and ultrasound-guided FNAB into
      routine endocrine practice. CONCLUSION: Routine performance of thyroid ultrasound
      in endocrine practice will considerably aid the management of nodular thyroid
      disease.

PMID- 20138597
TI  - A new way for improving the quality of colonoscopy?

PMID- 20138598
TI  - [Sputum induction in children: Technical development].
AB  - OBJECTIVE: To compare low and high flow nebulizers performance (total of samples)
      and its side effects on sputum induction in asthmatic children. PATIENTS AND
      METHODS: Sputum induction was performed by inhalation of a hypertonic saline
      solution at increasing concentrations (3%, 4% and 5%) using low flow (OMRON NE
      U07; flow rate 1ml/min), or high flow (OMRON NE-U12; flow rate 3ml/min, and
      DeVilbiss Ultraneb 3000; flow rate 2.5ml/min) ultrasonic nebulizers. RESULTS: We
      performed 49 inductions in 49 patients from 7 to 15 years old (in 15 children we
      used a low flow nebulizer (Omron NE-U07) and in 34 children a high flow nebulizer
      (OMRON NEU12, 6 patients, and DeVilbiss Ultraneb 3000, 28 patients). We obtained
      37 samples of which 36 had less than 20% of squamous cells, and 26 had a
      viability > or =60%. The test performance was higher with high-flow nebulizers,
      obtaining 85.3% of samples compared to 53% (p=0.04). A total of 69% of samples
      obtained with the high flow nebulizer were valid, compared to 62.5% (p=0.7) with
      the low flow nebulizers. With high flow rate nebulizers the incidence of cough
      (17.6%, p=0.08) and itchy eyes (0%, p=0.02) decreased with the low flow nebulizer
      (47% and 20% respectively), but bad taste (82.3%, p <0.001) and salivation
      (14.7%, p=0.3) increased. CONCLUSIONS: With high flow rate ultrasonic nebulizers
      we obtain a higher performance of the technique without an increase in
      significant side effects.

PMID- 20138599
TI  - [Clinical case: sulphur colloid scintigraphy, a diagnostic tool to differentiate
      between an infarction and osteomyelitis in a patient with drepanocytic anaemia].

PMID- 20138600
TI  - [Respiratory disease and diaphragm paralysis in Charcot-Marie-Tooth disease].
AB  - Diaphragmatic bilateral palsy is uncommon in children. The most important
      etiologies are thoracic surgery and obstetric trauma. Respiratory muscle
      impairment is a rare phenomenon in patients with Charcot-Marie-Tooth disease
      (CMT). However, it can be associated with restrictive pulmonary impairment,
      phrenic nerve dysfunction or thoracic cage abnormalities. We report two
      paediatric cases of CMT disease with type 2 respiratory failure due to
      diaphragmatic dysfunction. In both cases treatment with non-invasive mechanical
      ventilation resulted in satisfactory clinical improvement. Evidence of phrenic
      damage was the main clue in one patient in order to obtain an accurate diagnostic
      of her disease.

PMID- 20138601
TI  - Two-dimensional nanoarchitectonics based on self-assembly.
AB  - Top-down nanofabrication techniques, especially photolithography, have advanced
      nanotechnology to a point where system-process integration with bottom-up self
      assembly is now required. Because most lithographic techniques are constrained to
      two-dimensional planes, investigation of integrated self-assembly systems should
      focus on two-dimensional organization. In this review, research on two
      dimensional nanoartchitectonics is classified and summarized according to the
      type of interface used. Pattern formation following deposition of vaporized
      molecules onto a solid surface can be analyzed with high structural precision
      using scanning probe microscopy under ultra high vacuum. Transitions of adsorbed
      phases and adjustment of pattern mismatch by conformational changes of adsorbed
      molecules are discussed, in addition to the forces constraining pattern
      formation, i.e., two-dimensional hydrogen bond networks, van der Waals forces,
      and molecule-surface interactions. Molecular deposition at a liquid-solid
      interface broadens the range of molecules that can be investigated. The more
      complex molecules discussed in this work are C(60)-fullerene derivatives and
      designer DNA strands. Gas-liquid interfaces, e.g. between air and water, allow
      dynamic formations that can adjust to molecular conformational changes. In this
      case, any resulting patterns can be modulated by varying conditions
      macroscopically. Using flexible molecules at the fluid air-water interface also
      permits dynamic operation of molecular machines by macroscopic mechanical motion,
      thus enabling, hand-operated nanotechnology.

PMID- 20138602
TI  - Risk factors for radiation maculopathy after ophthalmic plaque radiation for
      choroidal melanoma.
AB  - PURPOSE: To determine how tumor characteristics and radiation dose affect the
      incidence of radiation maculopathy (RM). DESIGN: Retrospective, consecutive case
      series. METHODS: A consecutive case series of 384 uveal melanomas irradiated
      (mean apical dose, 71.2 Gy) were followed up for a mean 47.2 months. Tumor
      locations included: 122 (32%) centered anterior to the equator, 27 (7%)
      equatorial, and 235 (61%) posterior. Tumor sizes were American Joint Committee on
      Cancer class T1 (n = 180), T2 (n = 150), T3 (n = 47), and T4 (n = 7). RESULTS: RM
      occurred in 8 (7%) eyes with anterior uveal melanomas. In contrast, it was found
      in 82 (41%) eyes with posterior tumors. Multivariate analysis revealed the risk
      related to posterior location was greater compared with anterior location with a
      hazard ratio of 6.66 (95% confidence interval [CI], 4.94 to 22.50; P = .0001).
      Tumor height (> 6.0 mm) also demonstrated a high risk for RM (hazard ratio, 4.5;
      95% CI, 2.68 to 10.17; P = .0001). A significant dose-response relationship was
      found between dose to fovea and RM (P = .0005, for trend). As compared with a
      dose of < 35 Gy, the risk of RM was 1.74 (95% CI, 0.98 to 3.1) for doses from 35
      to 70 Gy, and the risk of RM was 2.43 (95% CI, 1.48 to 4.0) for doses of 70 Gy or
      more. Of interest, those anterior melanomas with RM had a mean apical height of
      9.4 mm, as compared with a mean height of 3.3 mm for anterior tumors not
      associated with RM. Visual acuity was preserved if the fovea dose was less than
      35 Gy. CONCLUSIONS: This study suggests that tumor location, tumor thickness, and
      radiation dose to the fovea are risk factors for the development of RM.

PMID- 20138603
TI  - Test-retest reliability of health-related quality-of-life questionnaires in
      adults with strabismus.
AB  - PURPOSE: To report the test-retest variability of two health-related quality-of
      life instruments: the new Adult Strabismus 20 (AS-20) and the National Eye
      Institute 25-item Visual Function Questionnaire (NEI VFQ-25), in adults with
      strabismus. DESIGN: Prospective case series. METHODS: Fifty-five adult patients
      in a clinical practice with stable strabismus completed the AS-20 and the NEI VFQ
      25 at 2 visits, without intervening treatment. Questionnaires were completed the
      second time either at a subsequent office visit, immediately before surgery, or
      by mail. Intraclass correlation coefficients were calculated. Ninety-five percent
      limits of agreement and 95% confidence intervals around the 95% limits of
      agreement also were calculated. RESULTS: There was excellent agreement of overall
      questionnaire scores for the AS-20 (intraclass correlation coefficient, 0.92) and
      NEI VFQ-25 (intraclass correlation coefficient, 0.94). The 95% limits of
      agreement for overall scores were 14.3 points (95% confidence interval, 10.9 to
      17.7) for the AS-20 and 11.1 points (95% confidence interval, 8.5 to 13.8) for
      the NEI VFQ-25. The lower test-retest variability of the VFQ-25 seemed to be
      partly the result of ceiling effects with many scores at the normal end of the
      range. CONCLUSIONS: The new AS-20 and the NEI VFQ-25 show excellent test-retest
      reliability in adults with strabismus. Change exceeding 95% limits of agreement
      (14 points on the AS-20 and 11 points on the VFQ-25) is indicative of real change
      in an individual patient. The AS-20 may be more useful than the VFQ-25 because it
      is less prone to ceiling effects in adults with strabismus.

PMID- 20138604
TI  - Outcomes and complications of rhegmatogenous retinal detachment repair with
      selective sutureless 25-gauge pars plana vitrectomy.
AB  - PURPOSE: To evaluate the outcomes and complications associated with the repair of
      rhegmatogenous retinal detachment (RRD) using 25-gauge pars plana vitrectomy
      (PPV) with selective sclerotomy suturing. DESIGN: Retrospective case series.
      METHODS: Analysis of consecutive 25-gauge pars plana vitrectomy cases performed
      for treating RRD was conducted. Reviewed parameters included demographics,
      ophthalmic history, results of ocular examinations, and intraoperative as well as
      postoperative complications. Analysis of the surgery digital video disc
      recordings revealed complications such as iatrogenic retinal breaks and retinal
      or subretinal tugging by the soft-tip cannula. RESULTS: Forty-two eyes with RRD
      were evaluated with a follow-up of at least 3 months. The preoperative best
      corrected visual acuity (BCVA) of 20 eyes with macula-on RRD ranged between 20/20
      and 20/40 (mean, 20/30). Twenty-two eyes with macula-off RRD had preoperative
      BCVA ranging between 20/70 and hand movements (mean, 20/400). The single-surgery
      success rate was 97.4%. The final BCVA of the macula-on eyes ranged between 20/20
      and 20/40 (mean, 20/30). In the eyes with macula-off RRD, the postoperative BCVA
      ranged between 20/30 and 20/400 (mean, 20/73). Sutures were placed on at least 1
      scleral wound because of intraoperative gas leakage in 36.4% of the eyes. On the
      first postoperative day, all the eyes receiving gas tamponade had a 100% fill.
      None of the eyes in the study had postoperative hypotony, ciliochoroidal
      effusion, or choroidal hemorrhage. No cases of postoperative subconjunctival gas
      or oil leakage were noted. CONCLUSIONS: Modification of the standard 25-gauge
      sutureless technique with selective scleral wound suturing may contribute to
      preventing wound leakage and possible postoperative complications of hypotony or
      partial tamponade.

PMID- 20138606
TI  - Tear measurement in prosthetic eye users with fourier-domain optical coherence
      tomography.
AB  - PURPOSE: To investigate whether Fourier-domain (FD) optical coherence tomography
      (OCT) can measure the tear meniscus of anophthalmic patients using prosthetic
      eyes and to compare the characteristics of normal and artificial eyes. DESIGN:
      Prospective, nonrandomized, observational case series. METHODS: Thirty-one
      patients who had undergone anophthalmic surgery in 1 eye and had been wearing
      artificial eyes for more than 6 months were included. Subjects with socket
      inflammation, contracted sockets, or other known lid disorders were excluded.
      Patients were asked to complete a questionnaire regarding their demographic
      status and dry eye symptoms before treatment, and FD OCT scanning and the
      Schirmer test were performed. Three images were obtained by FD OCT on each normal
      and anophthalmic eye, and the tear meniscus height, tear meniscus depth, and tear
      meniscus angle were measured with computer calipers. RESULTS: FD OCT was able to
      visualize the tear meniscus of both normal and artificial eyes. The mean tear
      meniscus height of artificial eyes was significantly lower than that of normal
      eyes (200.59 +/- 79.68 mum vs 261.24 +/- 86.17 mum; P < .001). Mean tear meniscus
      depth, tear meniscus area, and tear meniscus volume also were significantly lower
      in artificial eyes than in normal eyes. The dry eye symptom score showed
      significantly negative correlation with tear meniscus height. The Schirmer test
      results correlated with tear meniscus parameters in normal eyes, but not in
      artificial eyes. CONCLUSIONS: FD OCT is a valuable clinical tool in the
      evaluation of tear meniscus height in normal and artificial eyes. In addition,
      tear meniscus height can be a useful clinical parameter that estimates symptoms
      of ocular dryness and discomfort in both normal and artificial eyes.

PMID- 20138605
TI  - Ocular risk factors for age-related macular degeneration: the Los Angeles Latino
      Eye Study.
AB  - PURPOSE: To assess the association between ocular factors and age-related macular
      degeneration (AMD) in Latinos. DESIGN: Population-based, cross-sectional study of
      6357 self-identified Latinos aged 40 years and older. METHODS: Ophthalmic
      examination included subjective refraction, measurement of axial length,
      evaluation of iris color, Lens Opacities Classification System II (LOCS II)
      grading of cataracts, and stereoscopic macular photographs for AMD lesions.
      Generalized estimating equation analysis incorporated data from both eyes to
      estimate odds ratios (OR) adjusted for covariates. RESULTS: After controlling for
      confounders (age, gender, and smoking), prior cataract surgery was associated
      with advanced AMD (OR, 2.8; 95% CI, 1.01, 7.8), increased retinal pigment (OR,
      1.6; 95% CI, 1.02, 1.5), and retinal pigment epithelial depigmentation (OR, 2.2;
      95% CI, 1.1, 4.4). The presence of any lens opacity was associated with soft
      drusen (OR, 1.2; 95% CI, 1.002, 1.5). Longer axial length (per mm) was associated
      with decreased odds of soft drusen, increased retinal pigment, and geographic
      atrophy (GA) (ORs, 0.8 [95% CI, 0.7, 0.9], 0.8 [95% CI, 0.7, 0.9], 0.7 [95% CI,
      0.5, 0.9], respectively). Myopia was inversely associated with soft drusen (OR,
      0.8; 95% CI, 0.7, 0.99). Lighter-colored irises were associated with GA (OR, 5.0;
      95% CI, 1.0, 25.3). CONCLUSIONS: Cross-sectional associations of ocular factors
      such as cataract, cataract surgery, and refractive errors with early AMD lesions
      found in Latinos are consistent with those in non-Hispanic Whites. Additionally,
      prior cataract surgery was associated with advanced AMD.

PMID- 20138607
TI  - Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for
      keratoconus in Italy: the Siena eye cross study.
AB  - PURPOSE: To report the long-term results of 44 keratoconic eyes treated by
      combined riboflavin ultraviolet A collagen cross-linking in the first Italian
      open, nonrandomized phase II clinical trial, the Siena Eye Cross Study. DESIGN:
      Perspective, nonrandomized, open trial. METHODS: After Siena University
      Institutional Review Board approval, from September 2004 through September 2008,
      363 eyes with progressive keratoconus were treated with riboflavin ultraviolet A
      collagen cross-linking. Forty-four eyes with a minimum follow-up of 48 months
      (mean, 52.4 months; range, 48 to 60 months) were evaluated before and after
      surgery. Examinations comprised uncorrected visual acuity, best spectacle
      corrected visual acuity, spherical spectacle-corrected visual acuity, endothelial
      cells count (I Konan, Non Con Robo; Konan Medical, Inc., Hyogo, Japan), optical
      (Visante OCT; Zeiss, Jena, Germany) and ultrasound (DGH; Pachette, Exton,
      Pennsylvania, USA) pachymetry, corneal topography and surface aberrometry (CSO
      EyeTop, Florence, Italy), tomography (Orbscan IIz; Bausch & Lomb Inc., Rochester,
      New York, USA), posterior segment optical coherence tomography (Stratus OCT;
      Zeiss, Jena, Germany), and in vivo confocal microscopy (HRT II; Heidelberg
      Engineering, Rostock, Germany). RESULTS: Keratoconus stability was detected in 44
      eyes after 48 months of minimum follow-up; fellow eyes showed a mean progression
      of 1.5 diopters in more than 65% after 24 months, then were treated. The mean K
      value was reduced by a mean of 2 diopters, and coma aberration reduction with
      corneal symmetry improvement was observed in more than 85%. The mean best
      spectacle-corrected visual acuity improved by 1.9 Snellen lines, and the
      uncorrected visual acuity improved by 2.7 Snellen lines. CONCLUSIONS: The results
      of the Siena Eye Cross Study showed a long-term stability of keratoconus after
      cross-linking without relevant side effects. The uncorrected visual acuity and
      best spectacle-corrected visual acuity improvements were supported by clinical,
      topographic, and wavefront modifications induced by the treatment.

PMID- 20138608
TI  - Peripapillary dark choroid ring as a helpful diagnostic sign in advanced
      stargardt disease.
AB  - PURPOSE: To investigate the prevalence of a peripapillary dark choroid ring on
      fluorescein angiography (FA) and the associated clinical features in patients
      with Stargardt disease. DESIGN: Retrospective review of 135 patients with
      Stargardt disease. METHODS: The presence or absence of a peripapillary dark
      choroid ring on FA was noted and was compared with patient demographics and
      clinical features. RESULTS: Thirty-seven percent (50/135) had a peripapillary
      dark choroid ring on FA. When evaluated in subgroups, this sign was present in
      41% (9/22) of patients with 2 causative ABCA4 mutations, in 28% (5/18) of
      patients with 1 causative ABCA4 mutation and a clinical diagnosis of Stargardt
      disease, and in 38% (36/95) of patients with a clinical diagnosis of Stargardt
      disease pending mutational analysis. Ninety-four percent (44/47) of patients for
      whom mutational testing confirmed the presence of ABCA4 mutations demonstrated a
      dark choroid sign. The peripapillary dark choroid ring sign was associated with
      diffuse flecks (P < .001), worse logarithm of the minimal angle of resolution
      visual acuity (P = .03), larger central scotoma size (P = .0146), and the
      presence of complete macular atrophy (P = .0017) compared with patients without
      this sign. CONCLUSIONS: The presence of a peripapillary dark choroid ring on FA
      should prompt further evaluation for Stargardt disease by examination of
      peripheral retinal FA images for a dark choroid sign, followed by subsequent
      ABCA4 mutation screening.

PMID- 20138609
TI  - Evaluation of the aspheric tecnis multifocal intraocular lens: one-year results
      from the first cohort of the food and drug administration clinical trial.
AB  - PURPOSE: To evaluate the safety and effectiveness of the aspheric diffractive
      Tecnis multifocal ZM900 (TCMF) intraocular lens (IOL; Abbott Medical Optics, Inc,
      Santa Ana, California, USA). DESIGN: One-year, nonrandomized, multicenter,
      evaluator-masked, bilateral, parallel-group comparative clinical evaluation.
      METHODS: Subjects underwent bilateral implantation with the TCMF IOL or the CeeOn
      911A monofocal (CEMN) IOL (Abbott Medical Optics, Inc) according to subject
      preference. RESULTS: One-year results were available for 244 eyes of 125 TCMF IOL
      subjects and for 245 eyes of 123 CEMN IOL subjects. Mean distance visual acuities
      (VAs) were statistically and clinically equivalent between the 2 groups. Mean
      binocular and monocular uncorrected and distance-corrected near VAs were
      significantly better for the TCMF IOL versus the CEMN IOL group (P < .0001). A
      greater proportion of TCMF IOL versus CEMN IOL subjects achieved binocular
      combined VAs of 20/25 distance and 20/32 near (84.2% [96/114] vs 6.2% [7/113]; P
      < .0001). The TCMF IOL group had excellent depth of focus, maintaining a mean of
      20/40 or better for far, intermediate, and near distances. Mean contrast
      sensitivity scores were lower for the TCMF IOL versus the CEMN IOL group, but the
      differences were not considered clinically significant. Halos and night glare
      were more common in the TCMF IOL versus the CEMN IOL groups. Both reading acuity
      (20/20 vs 20/47; P < .0007) and speed (148 vs 117 words/minute; P < .0001) were
      significantly better for the TCMF IOL versus the CEMN IOL group, as were the
      proportions of the TCMF IOL group versus the CEMN IOL group that achieved
      spectacle independence (84.8% vs 5.2%; P < .0001) and that functioned comfortably
      at near without glasses (96.4% vs 30.4%; P < .0001). CONCLUSIONS: The TCMF IOL
      provided enhanced near VA, reading acuity per speed, depth of focus, and
      spectacle independence compared with the monofocal IOL.

PMID- 20138610
TI  - Observations by spectral-domain optical coherence tomography combined with
      simultaneous scanning laser ophthalmoscopy: imaging of the vitreous.
AB  - PURPOSE: To determine the ability to detect normal vitreous structure, evolving
      posterior vitreous detachment (PVD), and related vitreoretinal changes with
      combined spectral-domain optical coherence tomography (SD-OCT) and scanning laser
      ophthalmoscopy (SLO). DESIGN: Observational cross-sectional study. METHODS:
      Simultaneous SD-OCT and SLO imaging instruments (SD-OCT/SLO) were used to image
      both eyes of patients with symptoms of PVD. The vitreous cortex, preretinal
      lacunae, hyaloid, and its relations to the retinal surface were analyzed. In
      addition, ultrasound was performed in a subset of patients to determine the stage
      of PVD. RESULTS: Two-hundred two eyes of 113 subjects were scanned. There was a
      high correlation between diagnosis of complete PVD by clinical examination and
      OCT (95 vs 93 eyes, respectively; kappa, 0.82). A partial PVD was detected more
      frequently by SD-OCT/SLO than by biomicroscopy examination (45 vs 7 eyes; P <
      .0001). Ultrasound was performed in a subset of 30 eyes. A high agreement was
      found between ultrasound and SD-OCT/SLO results for both complete PVD (kappa,
      0.933) and incomplete PVD (kappa, 0.91). Vitreous cortex was detected in 181
      eyes, and posterior precortical vitreous pocket was detected in 85 eyes. The
      effects of PVD, including vitreoretinal traction, paravascular lamellar holes,
      and fine changes at the fovea, could be visualized reliably in detail only with
      SD-OCT/SLO. In all these eyes, SD-OCT/SLO allowed improved visualization of the
      vitreoretinal relationship. CONCLUSIONS: SD-OCT/SLO provides unprecedented in
      vivo information about the physiologic and pathologic vitreous structure; it
      allows an extremely detailed analysis of the vitreoretinal interface, and it is
      particularly useful for defining focal changes and PVD.

PMID- 20138611
TI  - Immunocytochemical detection of dentine matrix protein 1 in experimentally
      induced reactionary and reparative dentine in rat incisors.
AB  - OBJECTIVE: Although the general mechanisms of dentinogenesis are understood,
      several aspects regarding tertiary dentine formation still deserve investigation,
      especially regarding the presence and distribution of some noncollagenous matrix
      proteins. As dentine matrix protein 1 (DMP 1) is present in primary dentine, it
      is possible that this protein may also be present in the dentine matrix secreted
      after injury, but there are no immunocytochemical studies attempting its
      detection in tertiary dentine. The aim of this study was to examine the
      ultrastructural immunolocalization of DMP 1 in the tertiary dentine after
      extrusion of the rat incisor. STUDY DESIGN: Upper incisors were extruded 3mm and
      then repositioned into their sockets. After several periods, the incisors were
      fixed and processed for transmission electron microscopy and for
      immunocytochemistry for DMP 1. RESULTS: Extrusion yielded both types of tertiary
      dentine, which varied in aspect and related cells. DMP 1 was found in the
      mineralized matrix of all types of dentine, presenting high affinity for
      collagen, but rare colloidal gold particles over predentine. DMP 1 was evident in
      the supranuclear region and inside the nucleus of some odontoblast-like cells.
      CONCLUSION: The observed association between DMP 1 and collagen seem to be
      essential for reactionary and reparative dentine formation.

PMID- 20138612
TI  - "End-of-life" biases in moral evaluations of others.
AB  - When evaluating the moral character of others, people show a strong bias to more
      heavily weigh behaviors at the end of an individual's life, even if those
      behaviors arise in light of an overwhelmingly longer duration of contradictory
      behavior. Across four experiments, we find that this "end-of-life" bias uniquely
      applies to intentional changes in behavior that immediately precede death, and
      appears to result from the inference that the behavioral change reflects the
      emergence of the individual's "true self".

PMID- 20138613
TI  - A knowledge-driven probabilistic framework for the prediction of protein-protein
      interaction networks.
AB  - This study applied a knowledge-driven data integration framework for the
      inference of protein-protein interactions (PPI). Evidence from diverse genomic
      features is integrated using a knowledge-driven Bayesian network (KD-BN).
      Receiver operating characteristic (ROC) curves may not be the optimal assessment
      method to evaluate a classifier's performance in PPI prediction as the majority
      of the area under the curve (AUC) may not represent biologically meaningful
      results. It may be of benefit to interpret the AUC of a partial ROC curve whereby
      biologically interesting results are represented. Therefore, the novel
      application of the assessment method referred to as the partial ROC has been
      employed in this study to assess predictive performance of PPI predictions along
      with calculating the True positive/false positive rate and true positive/positive
      rate. By incorporating domain knowledge into the construction of the KD-BN, we
      demonstrate improvement in predictive performance compared with previous studies
      based upon the Naive Bayesian approach.

PMID- 20138614
TI  - Linked metabolites: a tool for the construction of directed metabolic graphs.
AB  - Metabolic pathway diagrams provide a wealth of information on how reactions
      combine to perform biological functions. While pathway diagrams are arranged in a
      way that allows a specific area of metabolism to be visualised, the inherent
      complexity of each pathway makes it difficult to identify the sets of reactions
      linking groups of compounds; a common task for researchers attempting to explain
      observed correlations or looking for further compounds of potential interest to
      use in validation work. Here we introduce Linked Metabolites, a tool that
      identifies sets of reactions linking groups of compounds in the context of the
      KEGG pathway diagrams.

PMID- 20138615
TI  - Intestinal Mycobacterium avium complex infection initially misdiagnosed and
      mistreated as Whipple disease.

PMID- 20138616
TI  - Transcecostomal colonic stent placement after US-guided percutaneous cecostomy.

PMID- 20138617
TI  - A gastric moonscape: lymph node penetration from subsequent Burkitt lymphoma
      after treatment of Hodgkin's lymphoma.

PMID- 20138618
TI  - Characteristics of HPV prevalence among women in Liaoning province, China.
AB  - OBJECTIVES: To investigate the prevalence rates of specific human papillomavirus
      (HPV) types infecting women in Liaoning Province, China. METHODS: Specimens from
      4780 patients with cervical disease and 165 age-matched controls were tested for
      HPV genotypes using a chip hybridization assay. RESULTS: The infection rates were
      35.66% for patients with cervicitis, 54.61% for those with ASCUS, 64.14% for
      those with CIN, 83.76% for those with cervical cancer in situ, and 83.12% for
      those with invasive cervical cancer. The most common HPV genotype was HPV-16,
      followed by HPV-58, HPV-52, HPV-33, HPV-53, and HPV-31. There were 1529 single
      and 731 multiple infections among the 4780 patients. Single infections with high
      risk genotypes were associated with various cervical diseases. HPV-16 was present
      in 399 of the patients with multiple infections. CONCLUSION: Compared with
      prevalence rates for other populations, the rates of specific HPV types infecting
      women are different in Liaoning Province of China.

PMID- 20138619
TI  - Pregnancy complications and obstetric outcomes among women with congenital
      uterine malformations.

PMID- 20138621
TI  - Estrogen attenuates vascular remodeling in Lp(a) transgenic mice.
AB  - OBJECTIVE: Although it is well known that Lipoprotein(a) (Lp(a)) is an
      atherogenic lipoprotein and an independent risk factor for cardiovascular
      disease, there is no confirmed therapy to decrease Lp(a) or prevent
      atherosclerosis induced by Lp(a). Thus, it is mandatory to develop novel therapy
      to prevent atherosclerosis in high Lp(a) concentration. Here, we focused on the
      effect of estrogen on Lp(a) level and Lp(a)-induced vascular remodeling. METHODS:
      We employed Lp(a) transgenic mice (human apo(a) yeast artificial chromosome (YAC)
      and human apoB double transgenic mice). Vascular remodeling was induced by
      ligation of the common carotid artery and the effect of estrogen was evaluated in
      female mice after ovariectomy with or without estrogen replacement. RESULTS:
      Estrogen deficiency caused by ovariectomy increased serum Lp(a), and continuous
      replacement of 17beta-estradiol (20 microg/kg/day) reversed the change. In the
      vascular remodeling model induced by carotid artery occlusion, neointima
      formation was significantly increased in ovariectomized female Lp(a) transgenic
      mice, but few in male Lp(a) transgenic mice, as compared to wild FVB mice.
      Importantly, continuous replacement of estrogen in ovariectomized mice
      significantly attenuated it. In cultured endothelial cells and macrophages,
      addition of Lp(a) increased mRNA of ICAM-1, VCAM-1, E-selectin and MCP-1 in
      endothelial cells and TNF-alpha, IL-1beta and MCP-1 in macrophages in a dose
      dependent manner. Importantly, pre-treatment with estrogen attenuated these
      changes in a dose-dependent manner. CONCLUSION: Estrogen negatively regulates
      both plasma Lp(a) level and Lp(a)-induced vascular remodeling, suggesting that
      estrogen might be a strong candidate to reduce serum Lp(a) concentration.

PMID- 20138620
TI  - Longitudinal association between toenail selenium levels and measures of
      subclinical atherosclerosis: the CARDIA trace element study.
AB  - OBJECTIVES: To examine the longitudinal association between toenail selenium
      levels and subclinical atherosclerosis over an 18-year period. METHODS: Toenail
      selenium concentrations were examined among 3112 Americans age 20-32 years in
      1987 and measured by instrumental neutron-activation analysis. Subclinical
      atherosclerosis, including common, bulb and internal carotid intima-media
      thickness (CIMT), was measured in 2005 and coronary artery calcium (CAC) score in
      2000 and 2005. General linear regression was developed examining the relation
      between toenail selenium levels and CIMTs, and logistic regression for repeated
      outcomes was employed estimating the risk of having CAC>0. RESULTS: After
      adjustment for potential confounders, no associations were observed between
      toenail selenium levels and CIMTs as well as CAC score. Comparing participants in
      the highest with the lowest quintile of selenium, the CIMT was 0.005 mm (SE=0.008
      mm, Ptrend=0.39), 0.018 mm (SE=0.019 mm, Ptrend=0.49), and 0.017 mm (SE=0.014 mm,
      Ptrend=0.21) thicker measured in common, bulb and internal carotid, respectively.
      The adjusted odds ratio of having CAC>0 was 0.95 (95% CI: 0.67-1.35;
      Ptrend=0.999). CONCLUSIONS: No associations were observed between toenail
      selenium and measures of subclinical atherosclerosis among American young adults.
      This study does not support an atherosclerotic mechanism of selenium for risk
      reduction of cardiovascular disease.

PMID- 20138622
TI  - Mycophenolic acid attenuates tumor necrosis factor-alpha-induced endothelin-1
      production in human aortic endothelial cells.
AB  - AIMS: Atherosclerotic cardiovascular disease is the major cause of morbidity and
      mortality in solid organ transplant recipients. Endothelin-1 (ET-1) is implicated
      in the pathogenesis of atherosclerosis and is one of the potential therapeutic
      targets. This study was conducted to evaluate the effect of mycophenolic acid
      (MPA), an immunosuppressant for the transplant recipients, on tumor necrosis
      factor-alpha (TNF-alpha)-induced ET-1 production in aortic endothelial cells.
      METHODS AND RESULTS: In cultured human aortic endothelial cells, TNF-alpha
      increased ET-1 through AP-1 and NF-kappaB, whereas MPA attenuated it by reducing
      both AP-1 and NF-kappaB DNA-binding activities. TNF-alpha increased ET-1 via c
      Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK),
      but not extracellular signal-regulated kinase. N-acetylcysteine that
      downregulated TNF-alpha-induced reactive oxygen species (ROS) inhibited JNK
      activation, but not p38 MAPK. N-acetylcysteine, SP600125 (JNK inhibitor) and
      SB203580 (p38 MAPK inhibitor) attenuated TNF-alpha-induced DNA-binding activities
      of both AP-1 and NF-kappaB. MPA inhibited JNK and p38 MAPK activations as well as
      ROS generation. N-acetylcysteine, SP600125, SB203580 and MPA had no effect on
      either TNF-alpha-induced IkappaBalpha degradation or p65 nuclear translocation,
      but attenuated p65 Ser276 phosphorylation. CONCLUSION: MPA attenuated TNF-alpha
      induced ET-1 production through inhibitions of ROS-dependent JNK and ROS
      independent p38 MAPK that regulated NF-kappaB as well as AP-1. These findings
      suggest that MPA could have an effect of amelioration of atherosclerosis.

PMID- 20138623
TI  - Cholesterol diet and effect of long-term withdrawal on plaque development and
      composition in the thoracic aorta of New Zealand White rabbits.
AB  - AIMS: Experimental study on plaque progression, regression and composition in
      atherosclerotic thoracic aorta of hypercholesterolemic rabbits after long-term
      withdrawal of cholesterol-enriched diet (CED). METHODS: Rabbits were fed 2%
      cholesterol for 6 weeks followed by withdrawal periods for 15, 23, 34, 68, or 78
      weeks. Cholesterol, triglyceride, and phospholipids levels in blood and
      cholesterol concentrations in aorta were quantified. Plaque size and cellularity,
      phenotype of macrophages and smooth muscle cells were
      (immuno)histomorphometrically analyzed in segments of the thoracic aorta.
      RESULTS: After 6 weeks of CED, blood cholesterol levels were about 80-fold
      higher, whereas atherosclerosis and cholesterol content in the thoracic aorta
      were only minimally increased. However, the latter significantly increased within
      15 weeks after cholesterol withdrawal, while serum cholesterol level was still 10
      fold increased. Thereafter plaque area and cholesterol content remained almost
      unchanged until the end of the study despite a long-term normalization of serum
      cholesterol level after withdrawal of CED. Directly after 6 weeks of CED the
      densities of macrophages and apoptotic cells within plaques were highest,
      decreasing after cholesterol withdrawal, whereas, vice versa the density of
      smooth muscle cells (SMCs) significantly increased. CONCLUSION: We suggest that
      atherosclerotic plaques respond to long-term withdrawal of CED by decrease in
      number and phenotype of macrophages and increase of SMCs without regression of
      the lesion size. The cellular changes are suggested to considerably contribute to
      higher plaque stability.

PMID- 20138624
TI  - Tocotrienol enriched palm oil prevents atherosclerosis through modulating the
      activities of peroxisome proliferators-activated receptors.
AB  - Palm oil is enriched in vitamin E in the form of alpha-, gamma-, and delta
      tocotrienols. Dietary tocotrienol supplements have been shown to prevent
      atherosclerosis development in patients and preclinical animal models. However,
      the mechanistic basis for this health beneficial effect is not well established.
      Peroxisome proliferator-activated receptors alpha, gamma, and delta (PPARalpha,
      PPARgamma, and PPARdelta) are ligand regulated transcription factors that play
      essential preventive roles in the development of atherosclerosis through
      regulating energy metabolism and inflammation. In this study, we presented data
      that the tocotrienol rich fraction (TRF) of palm oil activated PPARalpha,
      PPARgamma, and PPARdelta in reporter based assays. Importantly, TRF attenuated
      the development of atherosclerosis in ApoE-/- mice through inducing PPAR target
      gene liver X receptor alpha (LXRalpha) and its down-stream target genes
      apolipoproteins and cholesterol transporters, suggesting that modulating the
      activities of PPARs is a key aspect of the in vivo action of tocotrienols.

PMID- 20138625
TI  - An electrochemically enhanced solid-phase microextraction approach based on a
      multi-walled carbon nanotubes/Nafion composite coating.
AB  - In this paper, we proposed an approach using a multi-walled carbon nanotubes
      (MWCNTs)/Nafion composite coating as a working electrode for the
      electrochemically enhanced solid-phase microextraction (EE-SPME) of charged
      compounds. Suitable negative and positive potentials were applied to enhance the
      extraction of cationic (protonated amines) and anionic compounds (deprotonated
      carboxylic acids) in aqueous solutions, respectively. Compared to the direct SPME
      mode (DI-SPME) (without applying potential), the EE-SPME presented more effective
      and selective extraction of charged analytes primarily via electrophoresis and
      complementary charge interaction. The experimental parameters relating to
      extraction efficiency of the EE-SPME such as applied potentials, extraction time,
      ionic strength, sample pH were studied and optimized. The linear dynamic range of
      developed EE-SPME-GC for the selected amines spanned three orders of magnitude
      (0.005-1mugmL(-1)) with R(2) larger than 0.9933, and the limits of detection were
      in the range of 0.048-0.070ngmL(-1). All of these characteristics demonstrate
      that the proposed MWCNTs/Nafion EE-SPME is an efficient, flexible and versatile
      sampling and extraction tool which is ideally suited for use with chromatographic
      methods.

PMID- 20138626
TI  - On-line combination of single-drop liquid-liquid-liquid microextraction with
      capillary electrophoresis for sample cleanup and preconcentration: a simple and
      efficient approach to determining trace analyte in real matrices.
AB  - In order to improve the sensitivity of capillary electrophoresis (CE) and
      overcome the deficiency of commercial CE instruments in handling complex matrices
      directly, we proposed a novel technique which combined single-drop liquid-liquid
      liquid microextraction (SD-LLLME) with CE on-line. In this technique, SD-LLLME
      was realized using a commercial CE instrument and, to further concentrate the
      target analyte, large-volume sample stacking combined sweeping without polarity
      switching was utilized. Even though without agitating the donor phase in the
      extraction process, the model compound, adenine was enriched 550-fold in only 10
      min. The enrichment factors were 760 and 1030 when the extraction time was
      extended to 30 and 60 min, respectively. The relative standard deviations (RSDs)
      of adenine were 5.24% and 2.29% for peak area and migration time, respectively,
      which indicated that this method was much more reproducible compared to the
      existing methods that combined sample-preparation strategies with CE. In
      addition, this approach was selective while cleaning up target analyte. These
      mentioned advantages allowed the developed method to be an attractive approach to
      determining trace target compounds in complex real samples.

PMID- 20138627
TI  - Ultrasound-assisted surfactant-enhanced emulsification microextraction for the
      determination of carbamate pesticides in water samples by high performance liquid
      chromatography.
AB  - A novel ultrasound-assisted surfactant-enhanced emulsification microextraction
      (UASEME) coupled with high performance liquid chromatography-diode array
      detection has been developed for the extraction and determination of six
      carbamate pesticides (metolcarb, carbofuran, carbaryl, pirimicarb, isoprocarb and
      diethofencarb) in water samples. In the UASEME technique, Tween 20 was used as
      emulsifier, and chlorobenzene and chloroform were used as dual extraction solvent
      without using any organic dispersive solvent that is normally required in the
      previously described common dispersive liquid-liquid microextraction method.
      Parameters that affect the extraction efficiency, such as the kind and volume of
      the extraction solvent, the type and concentration of the surfactant, ultrasound
      emulsification time and salt addition, were investigated and optimized for the
      method. Under the optimum conditions, the enrichment factors were in the range
      between 170 and 246. The limits of detection of the method were 0.1-0.3 ng mL(-1)
      and the limits of quantification were between 0.3 and 0.9 ng mL(-1), depending on
      the compounds. The linearity of the method was obtained in the range of 0.3-200
      ng mL(-1) for metolcarb, carbaryl, pirimicarb, and diethofencarb, 0.6-200 ng mL(
      1) for carbofuran, and 0.9-200 ng mL(-1) for isoprocarb, with the correlation
      coefficients (r) ranging from 0.9982 to 0.9998. The relative standard deviations
      varied from 3.2 to 4.8% (n=5). The recoveries of the method for the six
      carbamates from water samples at spiking levels of 1.0, 10.0, 50.0 and 100.0 ng
      mL(-1) were ranged from 81.0 to 97.5%. The proposed UASEME technique has
      demonstrated to be simple, practical and environmentally friendly for the
      determination of carbamates residues in river, reservoir and well water samples.

PMID- 20138628
TI  - Optimized use of a 50mum ID secondary column in comprehensive two-dimensional gas
      chromatography-mass spectrometry.
AB  - The objective of the present research is directed towards the optimized use of a
      50microm ID secondary column, in a comprehensive two-dimensional gas
      chromatography-quadrupole mass spectrometry (GCxGC-qMS) system. The analytical
      aim was achieved by exploiting a split-flow GCxGC approach, and a rapid-scanning
      qMS instrument. The stationary phase combination consisted of an apolar
      (silphenylene polymer) 30mx0.25mm ID column, linked by means of a Y-union, to an
      MS-connected 1mx0.05mm ID polar one [poly(ethyleneglycol)], and to a 0.20mx0.05mm
      ID uncoated capillary segment; the latter was connected to a manually operated
      split-valve. It will be herein demonstrated that the split-flow GCxGC approach,
      successfully employed in previous H(2)-based, flame ionization detection
      experiments, provides equally satisfactory results using mass spectrometric
      detection and helium as carrier gas. An optimized split-flow GCxGC-qMS method was
      developed and exploited for the analysis of a perfume sample. The results
      attained were compared with those observed using the same analytical column
      combination, but with no flow-splitting. It was found that it is not convenient
      to employ a 50microm ID secondary column in a conventional GCxGC-MS instrument.
      On the contrary, the use a 50microm ID secondary column, in a split-flow, twin
      oven system, provided a good performance. A recently developed comprehensive
      chromatography software was used for data processing.

PMID- 20138629
TI  - Zirconium-doped and silicon-doped TiO2 photocatalysts synthesis from ionic-liquid
      like precursors.
AB  - Nanocrystalline titania powders doped with either zirconium or silicon were
      synthesized at low temperature via destabilization of ionic-liquid-like
      precursors. Titania materials prepared at low temperature (85 degrees C)
      consisted of anatase nanocrystals of about 25 nm, according to powder X-ray
      diffraction and transmission electron microscopy. Dopant incorporation was
      evaluated using inductively coupled plasma-optical emission spectrometry, and it
      was found that dopant/titanium ratios in the powder (0.011 for Zr and 0.026 for
      Si) were lower than those in the precursor (0.11 for both). Low-temperature
      nitrogen adsorption-desorption isotherms displayed the characteristic hysteresis
      loop of mesoporous materials. Specific surface areas reached values of 130 and
      155 m(2) g(-1) for Zr-doped and Si-doped TiO(2), respectively. The photocatalytic
      activity of the synthesized nanopowders was tested using methyl orange and 4
      chlorophenol as target pollutants.

PMID- 20138630
TI  - Photochemical formation of electrically conductive silver nanowires on polymer
      scaffolds.
AB  - A photochemical method has been exploited for the synthesis of electrically
      conductive silver (Ag) nanowires in a polymer solution in the presence of
      negatively charged Au seed particles. The synthesis was completed within 8 min of
      UV-photoirradiation in ambient conditions. The nanowires were fabricated on a PVA
      template having an average diameter of 135+/-20 nm and a length of 10-20 microm.
      The current-voltage (I-V) characterization showed that the PVA-Ag nanowires were
      continuous, having Ohmic behavior with low contact resistance. Results indicate
      that the PVA acted as a reducing agent, stabilizing agent, and a template for the
      nucleation and growth of Ag nanowires. The Ag deposition was highly selective and
      on the PVA only. Our research indicated that the PVA-Ag nanowires might be useful
      as interconnects in nanoscale integrated circuitry, functional nanodevices, and
      in optoelectronics.

PMID- 20138631
TI  - Studies on the conformational change of adsorbed BSA onto a moderately
      hydrophobic surface at different denaturant concentrations and surface coverages.
AB  - This paper is aimed at investigating the conformational change of denatured
      bovine serum albumin (BSA) in combination with thermodynamic functions and their
      fractions, adsorption isotherms, Fourier transform infrared (FTIR) spectroscopy,
      and differential scanning calorimetry (DSC). Microcalorimetric measurements of
      displacement adsorption enthalpies DeltaH of denatured BSA (by guanidine
      hydrochloride (GuHCl)) adsorbed onto a moderately hydrophobic surface (PEG-600)
      from solutions were carried out. The contents of secondary structure elements of
      BSA in solutions and in the adsorbed state were determined by FTIR and the
      thermal stability of adsorbed BSA was measured by DSC. The adsorption
      thermodynamic functions DeltaH, DeltaS, DeltaG, and their fractions were
      calculated based on the thermodynamics of the stoichiometric displacement theory
      for adsorption (SDT-A) and adsorption isotherms. The results showed that the
      surface can provide energy to denatured BSA and make it gain a more ordered
      conformation with GuHCl concentration increment. At a given GuHCl concentration,
      although the ordered secondary structure of adsorbed BSA molecules decreased,
      their tertiary structure may be more perfect with surface coverage increment. The
      thermodynamic analysis of four subprocesses associated with adsorption also
      confirmed the increment of conformational gain.

PMID- 20138632
TI  - Superhydrophobic PLA fabrics prepared by UV photo-grafting of hydrophobic silica
      particles possessing vinyl groups.
AB  - Superhydrophobic poly(lactic acid) (PLA) fabrics are prepared by UV photo
      grafting of hydrophobic silica particles possessing vinyl functional groups on
      the surfaces, which is a novel one-step process to provide surface with roughness
      as well as hydrophobicity simultaneously. For this purpose, hydrophobic silica
      particles with vinyl groups and average diameter of 1.51+/-0.05 microm are
      synthesized via a sol-gel process. The silica particles possessing vinyl groups
      are found to be effectively immobilized on PLA fabrics via UV photo-grafting
      reaction. The water contact angle of the treated PLA fabric is measured to be
      approximately 150 degrees, which is high enough to exhibit the Lotus effect as a
      result of the superhydrophobicity.

PMID- 20138633
TI  - Array comparative genomic hybridization as a diagnostic tool for syndromic heart
      defects.
AB  - OBJECTIVES: To investigate different aspects of the introduction of array
      comparative genomic hybridization (aCGH) in clinical practice. STUDY DESIGN: A
      total 150 patients with a syndromic congenital heart defect (CHD) of unknown
      cause were analyzed with aCGH at 1-Mb resolution. Twenty-nine of these patients,
      with normal results on 1Mb aCGH, underwent re-analysis with 244-K oligo
      microarray. With a logistic regression model, we assessed the predictive value of
      patient characteristics for causal imbalance detection. On the basis of our
      earlier experience and the literature, we constructed an algorithm to evaluate
      the causality of copy number variants. RESULTS: With 1-Mb aCGH, we detected 43
      structural variants not listed as clinically neutral polymorphisms, 26 of which
      were considered to be causal. A systematic comparison of the clinical features of
      these 26 patients to the remaining 124 patients revealed dysmorphism as the only
      feature with a significant predictive value for reaching a diagnosis with 1-Mb
      aCGH. With higher resolution analysis in 29 patients, 75 variants not listed as
      clinically neutral polymorphisms were detected, 2 of which were considered to be
      causal. CONCLUSIONS: Molecular karyotyping yields an etiological diagnosis in at
      least 18% of patients with a syndromic CHD. Higher resolution evaluation results
      in an increasing number of variants of unknown significance.

PMID- 20138634
TI  - The relationship of plasma transfusion from female and male donors with outcome
      after cardiac surgery.
AB  - OBJECTIVE: Pulmonary dysfunction is common in transfused patients recovering from
      heart surgery. Plasma transfusion from female donors has been linked with rare
      catastrophic lung injury, but its relationship with outcome after cardiac surgery
      is poorly understood. We examined whether plasma donor gender is related to
      postcardiac surgery pulmonary dysfunction and death or prolonged hospitalization.
      METHODS: In this retrospective case-control study, cardiac surgery candidates who
      received plasma perioperatively from only female donors were compared with male
      only recipients who were matched for the number of units transfused and surgery
      date. RESULTS: In a dataset of 2157 recipients, there were no blood bank-reported
      complications, but escalating plasma transfusion was associated with increased 30
      day mortality (odds ratio, 1.52 per unit; P = .0001). From the 1069 recipients
      receiving plasma exclusively from female or male donors, 390 matched pairs were
      identified. Recipients of female compared with male donor plasma had a lower
      incidence of pulmonary dysfunction (5.9% vs 10.8%; P = .01) and death or
      hospitalization more than 10 days (9% vs 16.4%; P = .002) but similar long-term
      survivals. CONCLUSIONS: Escalating plasma transfusion was associated with 30-day
      mortality, but female donor plasma recipients had less pulmonary dysfunction and
      fewer poor outcomes compared with male-only recipients. Although our
      retrospective study findings neither support nor refute a strategic policy to
      exclude female donor plasma to reduce catastrophic transfusion-related acute lung
      injury, they raise concern that such a policy may have unanticipated effects on
      outcome in patients undergoing cardiac surgery and highlight a need for
      additional studies in this and other patient groups.

PMID- 20138635
TI  - The effect of transplant center volume on survival after heart transplantation: a
      multicenter study.
AB  - OBJECTIVE: Few studies have examined the association between procedural volume
      and clinical outcomes in heart transplantation. This retrospective study was
      performed on a contemporary cohort of heart transplant recipients to better
      elucidate the effect of transplant center volume on 1-year mortality. METHODS:
      Data from the Scientific Registry of Transplant Recipients were used to analyze
      the relationship between transplant center volume and short-term survival. Center
      volume designation (very low, low, medium, and high) was assigned on the basis of
      quartiles with approximately equal numbers of patients per group. Survival
      differences were explored using Cox proportional hazards modeling to adjust for
      differences in variables between volume groups and to determine variables
      associated with 1-year mortality. RESULTS: Between January 1, 1999, and May 31,
      2005, 13,230 heart transplantations were performed at 147 transplant centers in
      the United States. Although most recipient and donor characteristics were similar
      across quartiles, larger volume centers were more likely to perform
      transplantations in older candidates and accept organs from older donors with
      longer cold ischemia times. A statistically significant relationship between
      transplant center volume and 1-year mortality was observed. Compared with the
      reference group (very low volume), the hazard ratios for the low, medium, and
      high-volume quartiles were 0.71, 0.64, and 0.56, respectively (P < .001 for each
      group compared with the reference). CONCLUSION: There was a significant
      association between transplant center volume and 1-year survival. Patients who
      undergo cardiac transplantation at very low-volume centers are at higher risk for
      early mortality than those who undergo transplantation in higher-volume centers.

PMID- 20138636
TI  - Cardiac dysfunction induced by experimental myocardial infarction impairs the
      host defense response to bacterial infection in mice because of reduced
      phagocytosis of Kupffer cells.
AB  - OBJECTIVE: This study was undertaken to investigate the effects of cardiac
      dysfunction induced by experimental myocardial infarction on the host defense
      response to bacterial infection and the role of Kupffer cells in mediating this
      response. METHODS: Myocardial infarction was induced in C57BL/6 mice by ligation
      of the left anterior descending coronary artery. Mice were challenged with
      Escherichia coli intravenously 1, 5, and 14 days after myocardial infarction or
      sham operation. Thereafter, the cytokine production and the function of their
      Kupffer cells were assessed. RESULTS: Mice with myocardial infarction showed
      remarkable cardiac dysfunction and had a significantly lower survival than sham
      mice after bacterial challenge at 5 days after surgery; bacterial challenge at 1
      or 14 days after surgery resulted in no difference in survival between myocardial
      infarction and sham mice. The phagocytic activity of Kupffer cells, assessed by
      fluorescein isothiocyanate microspheres, remarkably decreased in mice with
      myocardial infarction 5 days after surgery. Serum peaks of tumor necrosis factor
      and interferon-gamma after bacterial challenge were also suppressed in mice with
      myocardial infarction at 5 days. Production of these cytokines and immunoglobulin
      M from liver mononuclear cells was also impaired in mice with myocardial
      infarction. Enhancement of the phagocytic activity of Kupffer cells by C-reactive
      protein significantly improved survival after infection in mice with myocardial
      infarction, although neither interleukin-18 nor immunoglobulin-M treatment
      improved survival. CONCLUSIONS: Cardiac dysfunction induced by myocardial
      infarction renders mice susceptible to bacterial infection and increases
      mortality because of a reduced ability of Kupffer cells to clear infectious
      bacteria. C-reactive protein-enhanced phagocytic activity of Kupffer cells may
      improve the poor prognosis after bacterial infection in mice with myocardial
      infarction.

PMID- 20138637
TI  - [Malignant melanoma associated with blue naevus].

PMID- 20138638
TI  - [Foreword].

PMID- 20138639
TI  - [Gait disorders: mechanisms and classification].
AB  - Gait disorders are important because of their prevalence, particularly among the
      elderly, and the associated risk of falls and injury. The main physiological
      characteristics of locomotion and neural networks that organize locomotion and
      maintain balance are briefly reviewed. A simplified classification designed
      clinical practice and based upon clinical characteristics and more recent data
      obtained from quantified gait analysis is proposed.

PMID- 20138640
TI  - In vivo characterization of the aortic wall stress-strain relationship.
AB  - Arterial stiffness has been shown to be a good indicator of arterial wall
      disease. However, a single parameter is insufficient to describe the complex
      stress-strain relationship of a multi-component, non-linear tissue such as the
      aorta. We therefore propose a new approach to measure the stress-strain
      relationship locally in vivo noninvasively, and present a clinically relevant
      parameter describing the mechanical interaction between aortic wall constituents.
      The slope change of the circumferential stress-strain curve was hypothesized to
      be related to the contribution of elastin and collagen, and was defined as the
      transition strain (epsilon(theta)(T)). A two-parallel spring model was employed
      and three Young's moduli were accordingly evaluated, i.e., corresponding to the:
      elastic lamellae (E(1)), elastin-collagen fibers (E(2)) and collagen fibers
      (E(3)). Our study was performed on normal and Angiotensin II (AngII)-treated
      mouse abdominal aortas using the aortic pressure after catheterization and the
      local aortic wall diameters change from a cross-correlation technique on the
      radio frequency (RF) ultrasound signal at 30 MHz and frame rate of 8 kHz. Using
      our technique, the transition strain and three Young's moduli in both normal and
      pathological aortas were mapped in 2D. The slope change of the circumferential
      stress-strain curve was first observed in vivo under physiologic conditions. The
      transition strain was found at a lower strain level in the AngII-treated case,
      i.e., 0.029+/-0.006 for the normal and 0.012+/-0.004 for the AngII-treated
      aortas. E(1), E(2) and E(3) were equal to 69.7+/-18.6, 214.5+/-65.8 and 144.8+/
      55.2 kPa for the normal aortas, and 222.1+/-114.8, 775.0+/-586.4 and 552.9+/
      519.1 kPa for the AngII-treated aortas, respectively. This is because of the
      alteration of structures and content of the wall constituents, the degradation of
      elastic lamella and collagen formation due to AngII treatment. While such values
      illustrate the alteration of structure and content of the wall constituents
      related to AngII treatment, limitations regarding physical assumptions
      (isotropic, linear elastic) should be kept in mind. The transition strain,
      however, was shown to be a pressure independent parameter that can be clinically
      relevant and noninvasively measured using ultrasound-based motion estimation
      techniques. In conclusion, our novel methodology can assess the stress-strain
      relationship of the aortic wall locally in vivo and quantify important parameters
      for the detection and characterization of vascular disease.

PMID- 20138641
TI  - Differential expression and interaction of host factors augment HIV-1 gene
      expression in neonatal mononuclear cells.
AB  - We have previously shown a higher level of HIV-1 replication and gene expression
      in neonatal (cord) blood mononuclear cells (CBMC) compared with adult blood cells
      (PBMC), which could be due to differential expression of host factors. We
      performed the gene expression profile of CBMC and PBMC and found that 8013 genes
      were expressed at higher levels in CBMC than PBMC and 8028 genes in PBMC than
      CBMC, including 1181 and 1414 genes upregulated after HIV-1 infection in CBMC and
      PBMC, respectively. Several transcription factors (NF-kappaB, E2F, HAT-1, TFIIE,
      Cdk9, Cyclin T1), signal transducers (STAT3, STAT5A) and cytokines (IL-1beta, IL
      6, IL-10) were upregulated in CBMC than PBMC, which are known to influence HIV-1
      replication. In addition, a repressor of HIV-1 transcription, YY1, was down
      regulated in CBMC than PBMC and several matrix metalloproteinase (MMP-7, -12, 
      14) were significantly upregulated in HIV-1 infected CBMC than PBMC. Furthermore,
      we show that CBMC nuclear extracts interacted with a higher extent to HIV-1 LTR
      cis-acting sequences, including NF-kappaB, NFAT, AP1 and NF-IL6 compared with
      PBMC nuclear extracts and retroviral based short hairpin RNA (shRNA) for STAT3
      and IL-6 down regulated their own and HIV-1 gene expression, signifying that
      these factors influenced differential HIV-1 gene expression in CBMC than PBMC.

PMID- 20138642
TI  - Meteorological effects on the levels of fecal indicator bacteria in an urban
      stream: a modeling approach.
AB  - Gwangju Creek (GJC) in Korea, which drains a highly urbanized watershed, has
      suffered from substantial fecal contamination, thereby limiting the beneficial
      use of the water in addition to threatening public health. In this study, to
      quantitatively estimate the sinks and sources of fecal indicator bacteria (FIB)
      in GJC under varying meteorological conditions, two FIB (i.e., Escherichia coli
      and enterococci bacteria) were monitored hourly for 24h periods during both wet
      and dry weather conditions at four sites along GJC, and the collected data was
      subsequently used to develop a spatiotemporal FIB prediction model. The
      monitoring data revealed that storm washoff and irradiational die-off by sunlight
      are the two key processes controlling FIB populations in wet and dry weather,
      respectively. FIB populations significantly increased during precipitation, with
      greater concentrations occurring at higher rainfall intensity. During dry
      weather, FIB populations decreased in the presence of sunlight in daytime but
      quickly recovered at nighttime due to continuous point-source inputs. In this
      way, the contributions of the key processes (i.e., irradiational die-off by
      sunlight, settling, storm washoff, and resuspension) to the FIB levels in GJC
      under different meteorological conditions were quantitatively estimated using the
      developed model. The modeling results showed that the die-off by sunlight is the
      major sink of FIB during the daytime in dry weather with a minor contribution
      from the settling process. During wet weather, storm washoff and resuspension are
      equally important processes that are responsible for the substantial increase of
      FIB populations.

PMID- 20138643
TI  - History of Inuit community excretion of polychlorinated biphenyls recorded in
      sewage lake sediments.
AB  - Exposure to polychlorinated biphenyls (PCBs) is high among the Inuit resulting
      from ingestion of contaminated wild "country" foods. These contaminants originate
      in urban/industrial areas and reach the Arctic by long-range atmospheric
      transport. Ingested PCBs eventually equilibrate into various body components,
      including feces, which become an indication of body burden. Bulk domestic sewage
      residue from a community will accumulate PCBs from feces; long-term accumulated
      sediments from a sewage treatment system are a historical indicator of changes in
      community-wide PCB excretion. In this study, sediment cores were collected from
      the domestic sewage treatment lake, known as Annak, for the Inuit Hamlet of
      Sanikiluaq, Canada (established 1967), and were dated (Pb-210, Cs-137) and
      analyzed for 127 PCB congeners. We focused our attention on the 47 congeners that
      were observed consistently. Atmospheric and local inputs to a nearby lake
      accounted for local background. PCB inputs from sewage grew rapidly from the late
      1960s until 1990. The maximum 47 congener SigmaPCB excretion occurred in
      approximately 1989 (11116 ng person(-1)d(-1)); all sewage PCB inputs were
      dominated by PCB 153, PCB 138 and PCB 180. PCB ingestion from a Sanikiluaq food
      survey in 1989 for 11 of the most highly concentrated PCB congeners (7270 ng
      person(-1)d(-1)) was the same as our excretion estimate for the same congeners
      (7348 ng person(-1)d(-1)) that year, suggesting that by the late 1980s, the
      ingested amount of PCB was similar to what was excreted every day, although the
      latter is a reflection of body burden and not short-term exposure.

PMID- 20138644
TI  - HRGC/HRMS analysis of mirex in soil of Liyang and preliminary assessment of mirex
      pollution in China.
AB  - China is a country with the most severe termite damage in the world. Mirex is one
      of the two effective orgochlorine pesticides used in China for termite control. A
      high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS)
      was employed for mirex analysis in soil samples from Liyang city, which once was
      an important mirex production base in China. The detected mirex levels in soil in
      Liyang were 2.9-4300pgg(-1)dw (dry weight), with the geometric mean 26.83pgg(
      1)dw and the geometric standard deviation 5.02. The highest level occurred at the
      site near the Liyang Guanghua Chemical Factory. It implies the contribution of
      industrial activities to the mirex pollution in the surrounding environment.
      However, the factory only influenced very limited adjacent areas. A Level III
      fugacity model was developed to study the mirex pollution in Chinese provinces.
      The results show that the highest concentration occurred in Jiangxi Province,
      which has the largest consumption of mirex among Chinese provinces. On a regional
      scale, the calculated concentrations of mirex in the environment are generally so
      low that it indicates no harm to human and organisms. The total amount of mirex
      in the environment in China was estimated to be about 25.12tons, most of which
      exists in soil.

PMID- 20138645
TI  - Earthworms as colonisers: primary colonisation of contaminated land, and sediment
      and soil waste deposits.
AB  - This paper reviews the role of earthworms in the early colonisation of
      contaminated soils as well as sediment and waste deposits, which are worm-free
      because of anthropogenic activities such as open-cast mining, soil sterilisation,
      consistent pollution or remediation of contaminated soil. Earthworms live in
      close interaction with their soil environment and are able to change it
      considerably by their burrowing and litter comminuting behaviour. While
      earthworms have been studied extensively, several questions still remain
      unanswered such as: What are the characteristics of successful early colonisers?
      Do they function well in dispersal, individual establishment or population
      growth? Do the negative environmental conditions in these kinds of anthropogenic
      soils hamper colonization or are these colonizers relatively resistant to it? To
      what extent does colonization change the characteristics of the colonized
      substrate? In short, do earthworms impact the soil? In this paper, the
      characteristics that make earthworms successful colonisers are briefly described
      as well as which species are the most successful and under what circumstances,
      and what do earthworms contribute to the total process of succession. We propose
      that it is not so much eco-type or r-K strategy that govern success and
      succession of earthworm colonisation but rather environmental flexibility not
      only towards pH, desiccation, and temperature but also towards contaminants such
      as heavy metals. Moreover, the formation of an organic litter layer, in close
      connection with re-vegetation of the area, is essential for establishing
      earthworm populations, which, at first, are mainly superficially and shallow
      active species. The burrowing and organic matter digesting activity of these
      earthworms changes the upper soil to a well mixed humus layer suitable for deep
      burrowing earthworm species.

PMID- 20138646
TI  - Examining non-stationary effects of social determinants on cardiovascular
      mortality after cold surges in Taiwan.
AB  - Details about the impact of extreme cold on cardiovascular mortality are little
      known in the countries with warm winters like Taiwan. This study aimed to examine
      the ecological associations between various social determinants and
      cardiovascular mortality after cold surges in Taiwan with a spatial perspective
      focusing on spatial non-stationarity. The mortality rates at township level in
      Taiwan were observed from 1997 to 2003. Five social determinants (social
      disadvantage, lack of economic opportunity, stability, sensitive group, and
      rurality) were created with the 2000 Taiwan Census data. We analyzed the data
      using Geographically Weighted Poisson Regression. On average, an immediate
      increase in cardiovascular mortality was found right after cold surges. All of
      the five determinants were found to have spatial non-stationary effects on the
      cardiovascular mortality rates after cold surges. This finding provided an
      empirical basis for developing public health programs with local emphases on the
      impacts of extreme cold.

PMID- 20138647
TI  - Pathogens in septage in Vietnam.
AB  - Septage is widely acknowledged as a major source of infectious pathogens while
      disposal of septage, and the operation and maintenance of septic tanks, is not
      regulated in many developing countries. Twenty untreated septage and septage
      sludge samples were taken from Can Tho City, Vietnam to examine their pathogen
      content, and indicator micro-organisms. Escherichia coli and Enterococcus spp.
      were detected in all samples, regardless of sludge storage time. Phages were
      detected in 80% of samples. Salmonella spp. were detected in 70% of the untreated
      septage and 60% of septage sludge samples. Concentrations of phages and bacteria
      tested in septage sludge after many years of tank storage were much higher than
      the expected levels. Helminth ova were present in 95% of untreated septage
      samples with an average of 450 oval(-1), and were detected in all septage sludge
      samples with an average of 16,000 oval(-1). Twelve varieties of helminth ova were
      identified. More helminth ova varieties in higher concentrations were found in
      septage than those reported from stool samples. The varieties' frequency ranged
      from 10% to 50% and Ascaris lumbricoides predominated. Results show that
      pathogens and indicator micro-organisms, especially helminth ova, accumulate in
      sludge. Thus helminth ova should be considered when septage sludge is treated and
      used for agriculture. Proper health protection measures must be applied for
      people handling septage.

PMID- 20138648
TI  - Detection and estimation trends linked to air quality and mortality on French
      Riviera over the 1990-2005 period.
AB  - There is a profound relation between human health and well being from the one
      side and air pollution levels from the other. Air quality in South of France and
      more specifically in Nice, is known to be bad, especially in summer. The non
      parametric Mann-Kendall test has been developed for detecting and estimating
      monotonic trends in the time series and applied in our study at annual values of
      pollutants air concentrations and mortality. An important objective of many
      environmental monitoring programs is to detect changes or trends in pollution
      levels over time. Over the period 1990-2005, concerning the emissions of main
      pollutants, we obtained significant decreasing trends. By considering the ozone
      mean values in urban areas over the 1997-2005 period, an increase of 3.0% year(
      1) was obtained with annual averages and 3.9% year(-1) with median values. A
      clear increasing trend for PM(10) ambient concentrations is obtained. In
      addition, we observed an increase of the Olea (and Grass) pollination season.
      Over the same period, an annual change rate of +0.31% year(-1) for "airway
      diseases" and of +2.50% year(-1) for "unknown causes" were identified in the
      "Alpes Maritimes" county. To see the results, there seems to be a short-term link
      between the levels of these pollutants and mortality for respiratory causes. The
      other pollutants concentration showed a downward trend reflecting the reduction
      policy of the emissions. In addition, we obtained significant decreasing trends
      concerning the "ischemic heart diseases" (-1.20% year(-1)) and "asthma" (-4.03%
      year(-1)) categories. No significant gender-related difference was identified for
      these groups.

PMID- 20138649
TI  - A decision support tool to prioritize risk management options for contaminated
      sites.
AB  - The decisions on risk management (RM) of contaminated sites in Finland have
      typically been driven by practical factors such as time and money. However, RM is
      a multifaceted task that generally involves several additional determinants, e.g.
      performance and environmental effects of remediation methods, psychological and
      social factors. Therefore, we adopted a multi-criteria decision analysis approach
      and developed a decision support tool (DST) that is viable in decision-making in
      such a complex situation. The basic components of the DST are based on the Dutch
      REC system. However, our DST is more case-specific and allows the consideration
      of the type, magnitude and scale of contamination, land use, environmental
      conditions and socio-cultural aspects (e.g. loss of cultural heritage, image
      aspects). The construction of the DST was started by structuring the decision
      problem using a value tree. Based on this work we adopted the Multi-Attribute
      Value Theory (MAVT) for data aggregation. The final DST was demonstrated by two
      model sites for which the RM alternatives and site-specific data were created on
      the basis of factual remediation projects and by interviewing experts. The
      demonstration of the DST was carried out in a workshop where representatives of
      different stakeholders were requested to rank and weight the decision criteria
      involved. To get information on the consistency of the ranking of the RM
      alternatives, we used different weighting techniques (ratio estimation and pair
      wise weighting) and alternative ways to treat individual respondents' weights in
      calculating the preference scores for each RM alternative. These dissimilar
      approaches resulted in some differences in the preference order of the RM
      alternatives. The demonstration showed that attention has to be paid to the
      proper description of the site, the principles of the procedure and the decision
      criteria. Nevertheless, the procedure proved to enable efficient communication
      between different stakeholders and the identification of the preferred RM option.

PMID- 20138650
TI  - Mercury empirical relationships in sediments from three Ontario lakes.
AB  - Total mercury (THg), methyl mercury (MeHg), total organic carbon (TOC), sediment
      bulk density (SBD), redox potential (Eh) and percent fines measurements were made
      on sediment cores collected along transects from littoral to profundal depths in
      Harp, Dickie, and Blue Chalk lake located on the Canadian Shield near Dorset,
      Ontario, Canada to determine whether empirical relationships exist among these
      sediment properties. MeHg was positively correlated with THg in all sediments
      with a MeHg:THg ratio (0.004+/-0.004) comparable to other uncontaminated
      profundal lakes. MeHg, MeHg:THg and TOC decreased with sediment depth within the
      core for all lakes, whereas THg only showed a decrease in Harp Lake. MeHg:THg
      ratio in surficial sediments was positively correlated with Eh and negatively
      correlated with TOC [MeHg:THg=-0.009 TOC (%)+0.001 Eh (mV)-1.902, p=0.026];
      whereas THg was positively correlated with TOC [log THg (ppb)=0.026 TOC
      (%)+1.400, p<0.0001].

PMID- 20138651
TI  - Temperature-induced activation of freshwater Cyanophage AS-1 prophage.
AB  - Synechococcus sp. IU 625 is one of the freshwater cyanobacteria responsible for
      harmful algal blooms (HAB). Cyanophages can serve as natural control agents and
      may be responsible for algal bloom prevention and disappearance. Cyanophage AS-1,
      which infects Synechococcus sp. IU 625 (Anacystis nidulans) and Synechococcus
      cedrorum, plays an important role in the environment, significantly altering the
      numbers of its hosts. Since seasonal (temperature-dependent) lytic induction of
      cyanobacterial prophage has been proposed to affect seawater algal blooms, we
      investigated if the AS-1 lytic cycle could be induced by a shift to high
      temperature. Our hypothesis was confirmed, as more phages were released at 35
      degrees C than at 24 degrees C, with maximal induction observed with a shift from
      24 to 35 degrees C. Furthermore, transmission electron microscopy (TEM) images
      provide direct evidence of lysogenic to lytic conversion with temperature shift.
      Thus, temperature is an important inducer for AS-1 conversion from lysogenic to
      lytic cycle and could have applications in terms of modulating cyanobacterial
      populations in freshwater aquatic environments. The study gives insight into the
      effect of climate change on the interaction between cyanophage and cyanobacteria
      in freshwater ecosystems.

PMID- 20138652
TI  - WITHDRAWN: Immunohistochemical distribution of some regulatory peptides in the
      rat stomach.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 20138653
TI  - Acetylcholinesterase activity in an experimental rat model of Type C hepatic
      encephalopathy.
AB  - Patients with liver malfunction often suffer from hepatic encephalopathy, a
      neurological complication which can affect attention and cognition. Diverse
      experimental models have been used to study brain alterations that may be
      responsible for hepatic encephalopathy symptoms. The aim of the study was to
      determine whether cognitive impairment found in cirrhosis could be due to
      disturbance of acetylcholinesterase activity. Acetylcholinesterase activity was
      assessed in the brains of Wistar rats with thioacetamide-induced cirrhosis. The
      cirrhotic group displayed up-regulation of acetylcholinesterase levels in the
      entorrhinal cortex, anterodorsal and anteroventral thalamus and accumbens,
      whereas down-regulation was found in the CA1, CA3 and dentate gyrus of the
      hippocampus. Our results indicate that the experimental model of hepatic
      encephalopathy by chronic administration of thioacetamide presents alterations of
      acetylcholinesterase activity in brain limbic system regions, which play a role
      in attention and memory.

PMID- 20138654
TI  - Retroperitoneal Castleman's disease.
AB  - A 56-year-old postmenopausal woman with a history of colon cancer status after
      left hemicolectomy presented to our institution with abdominal pain, early
      satiety, and weight loss. Computerized tomography scan showed a large, enhancing,
      fat-containing mass displacing the left kidney posteriolaterally suspicious for a
      retroperitoneal liposarcoma. The lesion was also encasing the renal hilum. The
      patient underwent a wide excision of the mass as well as a radical nephrectomy
      and lymph node dissection by means of a thoracoabdominal approach. Final
      pathology revealed a large lymphatic mass consistent with Castleman's disease.

PMID- 20138655
TI  - Utility of urine cytology in the workup of asymptomatic microscopic hematuria in
      low-risk patients.
AB  - OBJECTIVES: To evaluate performance and cost-effectiveness of voided cytology in
      patients with pure asymptomatic microscopic hematuria (AMH). Although voided
      cytology has been validated for use in patients with a history of urothelial
      carcinoma (UC), its use in low-risk patients with AMH is controversial. METHODS:
      A total of 200 consecutive low-risk patients (median age, 64 years) with AMH were
      referred to the urology clinic between 2005 and 2007. All underwent cystoscopy,
      upper tract imaging, and voided urinary cytology. Results of voided cytology were
      classified as positive, atypical, or negative. Sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and costs were
      calculated. RESULTS: None had positive cytology, 23 (11.5%) had atypical
      cytology, and 177 (88.5%) had negative urinary cytology. Of 200 patients, 8 (4%)
      were found to have low-grade UC of bladder via cystoscopy; the cytology was
      negative in 4 patients and atypical in 4. Of 8, 4 were Ta and 4 were pT1 tumors.
      There was no upper urinary tract or renal malignancy identified. If atypical
      cytology was considered as positive, the sensitivity, specificity, PPV, and NPV
      of cytology were 50%, 90%, 17%, and 98%, respectively. If atypical cytology was
      considered as negative, the sensitivity, specificity, PPV, and NPV of cytology
      were 0%, 100%, 0%, and 96%, respectively. Cost of performing urinary cytology was
      estimated at $262.50 per patient. CONCLUSIONS: Although this study supports
      evaluating patients with AMH because a significant percentage of patients will
      have UC, voided urine cytology added a significant cost without any diagnostic
      benefit in the work-up of low-risk patients with AMH.

PMID- 20138656
TI  - Clinical parameters and semen analysis in 716 Austrian patients with varicocele.
AB  - OBJECTIVES: To evaluate different clinical parameters in association with the
      presence and severity of varicocele in a large group of Austrian men. METHODS:
      Records of 716 consecutive patients with clinical varicocele and infertility, who
      visited our andrology unit from 2001 to 2007, were retrospectively evaluated. The
      presence, grade, and side of any varicocele were recorded; varicoceles were
      confirmed by Doppler sonography. Semen samples, serum follicle-stimulating
      hormone, luteinizing hormone, estradiol, and testosterone levels were also
      assessed in all patients. RESULTS: Mean age was 29.6 +/- 0.3 years; 30% of
      patients presented with grade I varicocele, 39.0% with grade II, and 30.3% with
      grade III varicocele. About 33.3% of patients presented with normozoospermia,
      followed by asthenozoospermia (17.9%), oligoasthenoteratozoospermia syndrome
      (14.2%), and oligozoospermia (13.2%). Sperm density significantly decreased with
      increasing grade of varicocele. Body mass index was inversely proportional to
      varicocele. Serum testosterone levels were higher in grade III varicoceles (5.7
      +/- 0.2 nmol/L) compared with grade I (4.9 +/- 0.2 nmol/L) and grade II (5.0 +/-
      0.1 nmol/L) varicoceles (P <.001; range, 0.4-16.6 nmol/L). CONCLUSIONS: To our
      knowledge the current report is the first to describe a direct relationship
      between grade of varicocele and semen quality. Grade III varicocele was
      associated with decreased semen quality and, interestingly, with higher
      testosterone levels. Our study confirmed previous reports regarding the
      relationship between varicoceles and body mass index.

PMID- 20138657
TI  - Presence of human papillomavirus (HPV) in vulvar squamous cell carcinoma (VSCC)
      and sentinel node.
AB  - OBJECTIVE: To investigate the presence of HPV in VSCC and sentinel nodes (SN) in
      patients in Sweden and the possible influence of HPV on prognosis. PATIENTS AND
      MATERIALS: Primary tumors from 75 VSCC patients undergoing the SN procedure and
      SNs from 69 patients were tested for HPV DNA. Analyses were performed by PCR
      using general (GP5+/6+ and CPI/IIG) type-specific primers, and sequencing in
      paraffin-embedded VSCC and SN. RESULTS: HPV was detected in 23/75 (31%) of the
      tumors and in 10/23 (43%) of the SNs in patients with HPV-positive tumors and in
      one SN of a patient with an HPV-negative tumor. Patients with HPV-positive VSCC
      were younger at diagnosis (p<0.001) and had better survival (p=0.030), adjusted
      for age and lesion size, than those with HPV-negative tumors. In patients with
      HPV-positive tumors, SNs with metastases were more frequently HPV positive (5/5)
      than those without metastases (5/18) (p=0.007). CONCLUSION: The rate of 31% HPV
      positive VSCC in Sweden is similar to other reports. As far as we know, HPV in SN
      in VSCC never been investigated previously. The differences in age, tumor size,
      prevalence of HPV in SN and survival of patients with HPV-positive and negative
      VSCC support the assumption that VSCC develops through two different pathways,
      with better survival for patients with HPV-positive tumors. Presence of HPV DNA
      in SN was related to metastatic disease but did not affect survival in this
      study.

PMID- 20138658
TI  - Morphological/chemical imaging of demineralized dentin layer in its natural, wet
      state.
AB  - OBJECTIVE: Measuring the structure, composition or suitability for bonding of the
      acid-etched dentin substrate, especially in its hydrated state, has been a
      formidable problem. The purpose of this study was to determine the morphological
      and structural profiles of the dentin demineralized layer measured in its natural
      wet state using environmental scanning electron microscopy (ESEM) and micro-Raman
      imaging. MATERIALS AND METHODS: The occlusal 1/3 of the crown was removed from
      nine extracted, unerupted human third molars. Dentin surfaces were abraded with
      600-grit SiC sandpaper under water to create smear layers. The prepared dentin
      surfaces were randomly selected for treatment with the self-etching agent (Adper
      Prompt L-Pop) or the total-etching agent 35% H(3)PO(4) gel (with/without
      agitation). Micro-Raman spectra and imaging were acquired at 1-1.5microm spatial
      resolution at positions perpendicular to the treated surfaces; since this
      technique is non-destructive, the same specimens were also imaged with ESEM.
      Specimens were kept wet throughout spectral acquisition and ESEM observations.
      RESULTS: ESEM could be used to reveal demineralized layers in acid-etched dentin,
      but the resolution was low and no collagen fibrils were disclosed. The detailed
      chemical maps/profiles of demineralized dentin layers under wet conditions could
      be obtained using Raman imaging. It was shown that the mineral existed in the
      superficial layer of all etched dentin covered with smear layers. The mineral was
      much easier to be removed underneath the superficial layer. The depth, degree,
      and profile of dentin demineralization were dependent on the types of acids (self
      etching vs. total etching) and application procedures (with vs. without
      agitation). SIGNIFICANCE: Most current adhesives are applied using wet bonding
      techniques in which the dentin is kept fully hydrated throughout the bonding. Our
      ability to fully characterize the hydrated, etched dentin substrates is very
      important for understanding bonding under in vivo conditions.

PMID- 20138659
TI  - Effects of wave energy converters on the surrounding soft-bottom macrofauna (west
      coast of Sweden).
AB  - Offshore wave energy conversion is expected to develop, thus contributing to an
      increase in submerged constructions on the seabed. An essential concern related
      to the deployment of wave energy converters (WECs) is their possible impact on
      the surrounding soft-bottom habitats. In this study, the macrofaunal assemblages
      in the seabed around the wave energy converters in the Lysekil research site on
      the Swedish west coast and a neighbouring reference site were examined yearly
      during a period of 5 years (2004-2008). Macrobenthic communities living in the
      WECs' surrounding seabed were mainly composed by organisms typical for the area
      and depth off the Swedish west coast. At both sites the number of individuals,
      number of species and biodiversity were low, and were mostly small, juvenile
      organisms. The species assemblages during the first years of sampling were
      significantly different between the Lysekil research site and the nearby
      reference site with higher species abundance in the research site. The high
      contribution to dissimilarities was mostly due to polychaetes. Sparse macrofaunal
      densities can be explained by strong hydrodynamic forces and/or earlier trawling.
      WECs may alter the surrounding seabed with an accumulation of organic matter
      inside the research area. This indicates that the deployment of WECs in the
      Lysekil research site tends to have rather minor direct ecological impacts on the
      surrounding benthic community relative to the natural high variances.

PMID- 20138660
TI  - Biocompatible, hyaluronic acid modified silicone elastomers.
AB  - Although silicones possess many useful properties as biomaterials, their
      hydrophobicity can be problematic. To a degree, this issue can be addressed by
      surface modification with hydrophilic polymers such as poly(ethylene glycol), but
      the resulting structures are usually not conducive to cell growth. In the present
      work, we describe the synthesis and characterization of covalently linked
      hyaluronic acid (HA) (35 kDa) to poly(dimethylsiloxane) (PDMS) elastomer
      surfaces. HA is of interest because of its known biological properties; its
      presence on a surface was expected to improve the biocompatibility of silicone
      materials for a wide range of bioapplications. HA was introduced with a coupling
      agent in two steps from high-density, tosyl-modified, poly(ethylene glycol)
      tethered silicone surfaces. All materials synthesized were characterized by water
      contact angle, ATR-FTIR, XPS and (13)C solid state NMR spectroscopy. Biological
      interactions with these modified silicone surfaces were assessed by examining
      interactions with fibrinogen as a model protein as well as determining the in
      vitro response of fibroblast (3T3) and human corneal epithelial cells relative to
      unmodified poly(dimethylsiloxane) controls. The results suggest that HA
      modification significantly enhances cell interactions while decreasing protein
      adsorption and may therefore be effective for improving biocompatibility of PDMS
      and other materials.

PMID- 20138661
TI  - Morphological and mechanical characteristics of the reconstructed rat abdominal
      wall following use of a wet electrospun biodegradable polyurethane elastomer
      scaffold.
AB  - Although a variety of materials are currently used for abdominal wall repair,
      general complications encountered include herniation, infection, and mechanical
      mismatch with native tissue. An approach wherein a degradable synthetic material
      is ultimately replaced by tissue mechanically approximating the native state
      could obviate these complications. We report here on the generation of
      biodegradable scaffolds for abdominal wall replacement using a wet
      electrospinning technique in which fibers of a biodegradable elastomer,
      poly(ester urethane)urea (PEUU), were concurrently deposited with electrosprayed
      serum-based culture medium. Wet electrospun PEUU (wet ePEUU) was found to exhibit
      markedly different mechanical behavior and to possess an altered microstructure
      relative to dry processed ePEUU. In a rat model for abdominal wall replacement,
      wet ePEUU scaffolds (1x2.5 cm) provided a healing result that developed toward
      approximating physiologic mechanical behavior at 8 weeks. An extensive cellular
      infiltrate possessing contractile smooth muscle markers was observed together
      with extensive extracellular matrix (collagens, elastin) elaboration. Control
      implants of dry ePEUU and expanded polytetrafluoroethylene did not experience
      substantial cellular infiltration and did not take on the native mechanical
      anisotropy of the rat abdominal wall. These results illustrate the markedly
      different in vivo behavior observed with this newly reported wet electrospinning
      process, offering a potentially useful refinement of an increasingly common
      biomaterial processing technique.

PMID- 20138662
TI  - Effects of particle size and surface charge on cellular uptake and
      biodistribution of polymeric nanoparticles.
AB  - To elucidate the effects of particle size and surface charge on cellular uptake
      and biodistribution of polymeric nanoparticles (NPs), rhodamine B (RhB) labeled
      carboxymethyl chitosan grafted NPs (RhB-CMCNP) and chitosan hydrochloride grafted
      NPs (RhB-CHNP) were developed as the model negatively and positively charged
      polymeric NPs, respectively. These NPs owned well defined particle sizes (150-500
      nm) and Zeta potentials (-40 mV - +35 mV). FITC labeled protamine sulfate (FITC
      PS) loaded RhB-CMCNP and camptothecin (CPT) loaded RhB-CHNP with high
      encapsulation efficiency were prepared. The fluorescence stability in plasma and
      towards I(-) was investigated, and the result indicated it was sufficient for
      qualitative and quantitative analysis. NPs with high surface charge and large
      particle size were phagocytized more efficiently by murine macrophage. Slight
      particle size and surface charge differences and different cell lines had
      significant implications in the cellular uptake of NPs, and various mechanisms
      were involved in the uptake process. In vivo biodistribution suggested that NPs
      with slight negative charges and particle size of 150 nm were tended to
      accumulate in tumor more efficiently. These results could serve as a guideline in
      the rational design of drug nanocarriers with maximized therapeutic efficacy and
      predictable in vivo properties, in which the control of particle size and surface
      charge was of significance.

PMID- 20138663
TI  - Characterization of topographical effects on macrophage behavior in a foreign
      body response model.
AB  - Current strategies to limit macrophage adhesion, fusion and fibrous capsule
      formation in the foreign body response have focused on modulating material
      surface properties. We hypothesize that topography close to biological scale, in
      the micron and nanometric range, provides a passive approach without bioactive
      agents to modulate macrophage behavior. In our study, topography-induced changes
      in macrophage behavior was examined using parallel gratings (250 nm-2 mum line
      width) imprinted on poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA) and
      poly(dimethyl siloxane) (PDMS). RAW 264.7 cell adhesion and elongation occurred
      maximally on 500 nm gratings compared to planar controls over 48 h. TNF-alpha and
      VEGF secretion levels by RAW 264.7 cells showed greatest sensitivity to
      topographical effects, with reduced levels observed on larger grating sizes at 48
      h. In vivo studies at 21 days showed reduced macrophage adhesion density and
      degree of high cell fusion on 2 mum gratings compared to planar controls. It was
      concluded that topography affects macrophage behavior in the foreign body
      response on all polymer surfaces examined. Topography-induced changes,
      independent of surface chemistry, did not reveal distinctive patterns but do
      affect cell morphology and cytokine secretion in vitro, and cell adhesion in vivo
      particularly on larger size topography compared to planar controls.

PMID- 20138664
TI  - Bioactive hydrogels made from step-growth derived PEG-peptide macromers.
AB  - Synthetic hydrogels based on poly(ethylene glycol) (PEG) have been used as
      biomaterials for cell biology and tissue engineering investigations. Bioactive
      PEG-based gels have largely relied on heterobifunctional or multi-arm PEG
      precursors that can be difficult to synthesize and characterize or expensive to
      obtain. Here, we report an alternative strategy, which instead uses inexpensive
      and readily available PEG precursors to simplify reactant sourcing. This new
      approach provides a robust system in which to probe cellular interactions with
      the microenvironment. We used the step-growth polymerization of PEG diacrylate
      (PEGDA, 3400Da) with bis-cysteine matrix metalloproteinase (MMP)-sensitive
      peptides via Michael-type addition to form biodegradable photoactive macromers of
      the form acrylate-PEG-(peptide-PEG)(m)-acrylate. The molecular weight (MW) of
      these macromers is controlled by the stoichiometry of the reaction, with a high
      proportion of resultant macromer species greater than 500kDa. In addition, the
      polydispersity of these materials was nearly identical for three different MMP
      sensitive peptide sequences subjected to the same reaction conditions. When
      photopolymerized into hydrogels, these high MW materials exhibit increased
      swelling and sensitivity to collagenase-mediated degradation as compared to
      previously published PEG hydrogel systems. Cell-adhesive acrylate-PEG-CGRGDS was
      synthesized similarly and its immobilization and stability in solid hydrogels was
      characterized with a modified Lowry assay. To illustrate the functional utility
      of this approach in a biological setting, we applied this system to develop
      materials that promote angiogenesis in an ex vivo aortic arch explant assay. We
      demonstrate the formation and invasion of new sprouts mediated by endothelial
      cells into the hydrogels from embedded embryonic chick aortic arches.
      Furthermore, we show that this capillary sprouting and three-dimensional
      migration of endothelial cells can be tuned by engineering the MMP-susceptibility
      of the hydrogels and the presence of functional immobilized adhesive ligands
      (CGRGDS vs. CGRGES peptide). The facile chemistry described and significant
      cellular responses observed suggest the usefulness of these materials in a
      variety of in vitro and ex vivo biologic investigations, and may aid in the
      design or refinement of material systems for a range of tissue engineering
      approaches.

PMID- 20138665
TI  - Sperm associated antigen 9 expression and humoral response in chronic myeloid
      leukemia.
AB  - Early diagnosis and cure for patients with chronic myeloid leukemia (CML) exhibit
      significant clinical challenges because of the disease progression from chronic
      phase (CP) into a rapidly fatal blast crisis. Our earlier studies suggested an
      association of sperm associated antigen 9 (SPAG9) with various human
      malignancies. The present investigation revealed that SPAG9 mRNA and protein are
      expressed in CML patients (88%), in K562 and KCL-22 cells. Further, SPAG9 protein
      expression was also detected on cell surface suggesting that this molecule may be
      a suitable target for immunotherapy. Interestingly, 90% CML-CP patients showed
      humoral response against SPAG9, suggesting its important role in early diagnostic
      of CML-CP. Further investigation is warranted in establishing the potential of
      SPAG9 as a biomarker and immunotherapeutic target for early treatment of CML-CP
      patients.

PMID- 20138666
TI  - The essential roles of matrix metalloproteinase-2, membrane type 1
      metalloproteinase and tissue inhibitor of metalloproteinase-2 in the invasive
      capacity of acute monocytic leukemia SHI-1 cells.
AB  - The frequency of extramedullary infiltration (EMI) in acute myeloblastic leukemia
      (AML) is reported up to 40% and most prevalent in myelo-monoblastic and
      monoblastic subtypes of AML (M4 and M5 according to FAB classification). The
      majority of patients with EMI suffered poor prognosis. To explore mechanism
      underlying EMI, we analyzed SHI-1 cells, a highly invasive human acute monocytic
      leukemia cell line, and found their strong expression of matrix metalloproteinase
      2 (MMP-2), membrane type 1 MMP (MT1-MMP) and tissue inhibitor of
      metalloproteinase 2 (TIMP-2). SHI-1 cells showed higher invasive ability to
      traverse reconstituted basement membranes (Matrigel) and stronger activation of
      proMMP-2 than other leukemia cell line such as NB4, K562, U937 and THP-1 cells.
      When co-cultured with bone marrow stromal cells (BMSCs), the invasive capacity
      and proMMP-2 activation of SHI-1 cells enhanced remarkably. Furthermore, the
      inhibition of MMP-2, MT1-MMP, or TIMP-2 by small interfering RNA (siRNA)
      substantially impaired SHI-1 cells invasion and decreased proMMP-2 activation. In
      the contrast, up-regulated expression of TIMP-2 for 2-3 folds level increased
      cell invasion and proMMP-2 activation. These results demonstrated that
      constitutively high expression of MMP-2, MT1-MMP and TIMP-2 in SHI-1 cells
      facilitated cell invasion by promoting proMMP-2 activation. Moreover, up
      regulation of TIMP-2 exhibited not a repressive but an activating effect on SHI-1
      cells invasion. Our study indicated that increasing TIMP-2 in AML patients with
      EMI may potentially cause adverse effects, particularly in patients containing
      high levels of MMP-2 and MT1-MMP.

PMID- 20138667
TI  - Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio
      cytarabine:daunorubicin formulation, in bone marrow xenografts.
AB  - The objective of this study was to examine the pharmacodynamic basis for the
      potent preclinical and clinical anti-leukemic activity of CPX-351, a nano-scale
      liposome formulation of cytarabine and daunorubicin co-encapsulated at a
      synergistic 5:1 molar ratio. A bone marrow-engrafting CCRF-CEM leukemia model in
      Rag2-M mice was utilized to correlate the therapeutic and myelosuppressive
      properties of CPX-351 with bone marrow delivery and drug uptake in leukemia cells
      relative to normal bone marrow cell populations. When administered to mice
      bearing CCRF-CEM human leukemia xenografts, CPX-351 ablated bone marrow (BM)
      leukemic cells to below detectable levels for multiple weeks, whereas the free
      drug cocktail only transiently suppressed leukemia growth. In contrast to the
      activity against leukemia cells, CPX-351 and free-drug cocktail induced similar
      myelosuppression in non-tumor-bearing BM. In leukemia-laden BM, drug
      concentrations were markedly elevated for CPX-351 over free-drug cocktail and the
      first dose of CPX-351, but not free-drug cocktail, potentiated BM drug
      accumulation for subsequent doses. Confocal fluorescence microscopy revealed that
      CPX-351 liposomes are taken up by CCRF-CEM cells and subsequently release drugs
      intracellularly. The improved in vivo efficacy of CPX-351 appears related to
      increased and prolonged exposure of synergistic cytarabine:daunorubicin ratios in
      BM, and the selective killing of leukemia may arise from direct liposome-leukemia
      cell interactions. These features may also have broader applicability in the
      treatment of other haematological malignancies.

PMID- 20138668
TI  - An extraterrestrial sandwich: The perils of food in space.
AB  - Food was and is an essential component in human space exploration. If it had not
      proved possible to eat and digest in space, none of the long-term space missions
      of the last four decades would have been achievable. Every country that has sent
      an astronaut on a mission has used its national foods as a means of stating both
      their presence and their identity to their colleagues in the programme and their
      citizens at home: in space, as on earth, food has provided a means of asserting
      national culture. From the earliest missions, the US and USSR's differing
      attitudes to the programme have been reflected in the food provided and the
      respective administrations' approaches to feeding in space. The contrast between
      the US focus on space travel and the USSR's focus on space living is highlighted
      through their attitudes to the often vexed question of what astronauts and
      cosmonauts should be permitted to eat, illustrated by the corned-beef sandwich
      incident of 1965.

PMID- 20138669
TI  - Silencing of C5a receptor gene with siRNA for protection from Gram-negative
      bacterial lipopolysaccharide-induced vascular permeability.
AB  - Endothelial barrier dysfunction leading to increased permeability and vascular
      leakage is an underlying cause of several pathological conditions. Whereas these
      changes have been shown to be associated with activation of the complement
      system, leading to the release of C5a and interaction of C5a-C5a receptor (C5aR),
      the role of C5aR in endothelial cells remain(s) ill-defined. Here, we report an
      essential role of C5aR in endothelial cell injury and vascular permeability
      through silencing of the C5aR gene using siRNA. In the cultured mouse dermal
      microvascular endothelial cells (MEMECs) monolayer transfected with C5aR-siRNA,
      endotoxin-induced cell injury by evaluated as transendothelial flux, cell
      detachment, and cytoskeletal disorganization was inhibited. Upregulation of
      vascular cell adhesion molecule-1 (VCAM-1) was also suppressed. Studies exploring
      the underlying mechanism of siRNA-mediated suppression in VCAM-1 expression were
      related to reduction of NF-kappaB activation and nuclear localization of both p50
      and p65. The effect was associated with inhibition in activation of protein
      kinase Cdelta(PKC-delta) and induction of PKC-mediated mitogen-activated protein
      kinase phosphatases-1 (MKP-1) leading to the increased activity of p42/p44
      mitogen-activated protein (MAP) kinase cascade. In the model of mice
      administrated with C5aR-siRNA, endotoxin-induced plasma leakage was inhibited in
      local abdominal skin. Systemic administration of endotoxin to mice resulted in
      increased microvascular permeability in multiple organs was reduced. These
      studies demonstrate that the C5aR responsible for vascular endothelial cell
      injury and plasma permeability is an important factor, and that blockade of C5aR
      may be useful therapeutic targets for the prevention of vascular permeability in
      pathogenic condition.

PMID- 20138670
TI  - Tehranolide molecule modulates the immune response, reduce regulatory T cell and
      inhibits tumor growth in vivo.
AB  - Tehranolide named as new type of a sesquiterpene lactone with an endoperoxide
      group which purified from Artemisia diffusa and having similar structure to
      Artemisinin. Tehranolide is hypothesized to possess effects akin to Artemisinin,
      which is active against cancer cells. In the present research we emphasized on
      the direct correlation between the tumor sizes, immune response; including
      cytokin network, T regulatory cells and Tehranolide intraperitoneally injected
      Tehranolide. In this study, Tehranolide was purified from Artemisia difussa.
      First we evaluated the effects of Tehranolide on cell growth inhibition (in
      vitro) by MTT assay and second investigated the immune responses, these include
      measuring tumor growth in the female Balb/c mice transplanted with spontaneous
      mouse mammary tumor and treated with Tehranolide, splenocyte proliferation
      detected by using the BrdU kit, measurement of cytokine profile by ELISA and
      analysis of T-lymphocytes subpopulation in spleen by Flow cytometry. Our results
      showed a significant (p<0.05) decrease in the tumor volume and the level of IL-4
      in the animals treated with Tehranolide, compared to untreated group. In
      addition, a significant (p<0.05) increase in the lymphocytes proliferation and
      the level of IFN-gamma in the animals treated with Tehranolide in comparison with
      control group. Furthermore, we regulate the regulatory T cells in order to
      improve the outcome of cancer immunotherapy. The measurement of splenic
      CD4(+)CD25(+)Foxp3(+) T lymphocytes indicated that Tehranolide significantly
      (p<0.05) decreased the number of these lymphocytes. These findings show that the
      use of Tehranolide molecule represents a novel strategy with major suggestions
      for cancer therapy approaches.

PMID- 20138671
TI  - The stability of parental bonding reports: a 20-year follow-up.
AB  - BACKGROUND: Addressing the long-term reliability of retrospectively assessed
      parenting is underscored by the well-documented association between parenting
      behaviors, and mood disorders in offspring. The rarity of longitudinal research
      with follow-up periods exceeding 10 years creates a need for additional studies.
      METHODS: 134 offspring of depressed and non-depressed parents were assessed on
      Parental Bonding Instrument (PBI) scores, lifetime major depression (MDD), and
      current depressive symptoms at four waves across 20 years. PBI rank order and
      mean level stability, individual trajectories, and the impact of baseline age,
      gender, and lifetime MDD on stability, were obtained using multiple regression
      and linear mixed model analyses. RESULTS: Besides paternal overprotection which
      showed a 1.6-point average decrease, the PBI domains remained non-significant for
      mean level change over 20 years. However, there was a significant individual
      variation for all PBI domains. Lifetime MDD and age did not significantly impact
      retest correlations; older age at baseline was associated with higher average
      paternal overprotection. Sons had lower retest correlations than daughters, but
      did not differ from daughters on mean level stability. Current depressive
      symptoms were associated with PBI scores, but did not impact the effect of
      lifetime MDD, gender or age on mean level stability and individual trajectories.
      LIMITATIONS: Small sample sizes and measuring lifetime MDD as present or absent
      may have restricted our ability to detect effects of MDD history on PBI
      stability. CONCLUSION: The PBI is a robust measure of an important environmental
      risk for depressive disorders, and can be variably sensitive to sample
      characteristics, the passage of time and mood fluctuations. However, this
      sensitivity does not appear to significantly bias the long-term stability of this
      instrument.

PMID- 20138672
TI  - Emerging role of estrogen in the control of cardiometabolic disease.
AB  - Menopause is associated with an increased risk of cardiovascular and metabolic
      disease that is partly independent of aging. This increased risk is largely due
      to postmenopausal estrogen loss. Estrogen improves insulin sensitivity and ss
      cell function. This is consistent with the increased risk of diabetes after
      menopause and the finding that menopausal hormone therapy (MHT) lowers the
      incidence of diabetes. Experimental data suggest that estrogen has anti
      atherosclerotic and pro-thrombotic properties. This is consistent with
      observational and interventional studies suggesting that MHT reduces the risk of
      cardiovascular disease if initiated early in women with a low-risk profile, but
      might increase risk in older women and/or those with other risk factors (e.g.
      dyslipidemia). Future research focusing on improving prevention of
      cardiometabolic disease through MHT may help to identify agents with higher
      tissue- and estrogen receptor-isoform specificity than currently used hormones.

PMID- 20138673
TI  - Should I stay or should I go? Becoming a granule cell.
AB  - Cerebellar granule cells undergo profound and rapid morphological modifications
      during development while they migrate from their birthplace at the surface of the
      cerebellar cortex to its deepest layer. Post-mitotic granule cells extend bipolar
      axons and sequentially use the two main modes of migration, tangential and
      radial, to reach their final destinations. Recent studies show that protein
      degradation involving key cell-cycle regulators controls granule cell axon
      extension. The use of knockout mice deficient in different axon-guidance
      molecules combined with cutting-edge imaging methods has started to shed light on
      the molecular mechanisms that trigger granule cell migration. These studies
      suggest that a major reorganization of the cytoskeleton occurs as granule cells
      switch from tangential to radial migration.

PMID- 20138674
TI  - New frontiers of cognitive rehabilitation in geriatric age: the Mozart Effect
      (ME).
AB  - The ME was described for the first time in 1993. Subsequently other studies with
      similar designs were performed. The present study, therefore, proposes: (i) to
      verify the existence of the benefits of exposure to music in elderly subjects
      with mild cognitive impairment (MCI), (ii) to explore whether it is possible to
      find any lasting improvement after training, conducted for a long period of time,
      with such musical pieces, in the measurable cognitive performances. The study we
      conducted showed that the ME is present in geriatric patients with MCI; the
      influence on spatial-temporal abilities remains constant in time if the
      stimulation is maintained. The continuation of our study will consist of
      increasing the number of individuals examined and in having them listen to music
      during the study of ECG rhythms and during the acquisition of cerebral functional
      magnetic resonance imaging (fMRI), and, at the same time, testing them by
      neuropsychometric methods.

PMID- 20138675
TI  - Health and functional status and utilization of health care services among
      holocaust survivors and their counterparts in Israel.
AB  - To examine differences in health and functional status and in utilization of
      health services between holocaust survivors and their counterparts; and (b) to
      investigate if holocaust survivor status is a significant predictor of health
      status, functional status, and utilization of health services. The study included
      1255 respondents of whom 272 were holocaust survivors. Interviews were conducted
      face-to-face at the respondents' homes. Participants were asked about their
      health (self-rated health and comorbidity) and functional (ADL and IADL) status,
      utilization of inpatient and outpatient health care services, age, gender,
      education, marital status, length of residence in Israel, and if they were
      holocaust survivors. Holocaust survivors, who were frailer and more chronically
      ill compared to their counterparts, visited their family physician and the nurse
      at the health care clinic more often than their counterparts did, and received
      more homecare services. Yet, there were no differences between them in the
      utilization of other health care services such as visits to specialists,
      emergency department, and hospitalizations. Holocaust survivors are more
      homebound due to more morbidity and functional limitations and therefore receive
      more health home care services that offset the utilization of other health
      services.

PMID- 20138676
TI  - Recent advances in the echocardiographic diagnosis of mitral valve prolapse.

PMID- 20138677
TI  - Cardiac syndrome X: current concepts.
AB  - Cardiac syndrome X is a heterogeneous entity, both clinically and
      pathophysiologically, encompassing a variety of pathogenic mechanisms. Management
      of this syndrome represents a major challenge to the treating physician. They
      often seek medical care because of recurring and disabling chest pain, which may
      imply repetitive and costly invasive and non-invasive investigations. A careful
      patient evaluation for underlying pathophysiologic mechanism and exclusion of
      other causes of chest pain along with attention to various psychological aspects
      is helpful in reducing the stress and suffering of these patients. This article
      reviews the available literature on the pathophysiology and current controversies
      surrounding the management of this difficult to treat condition.

PMID- 20138679
TI  - Consequences of eliminating federal disability benefits for substance abusers.
AB  - Using annual, repeated cross-sections from national household surveys, we
      estimate how the January 1997 termination of federal disability insurance,
      Supplemental Security Income (SSI), for those with Drug Addiction and Alcoholism
      affected labor market outcomes among individuals targeted by the legislation. We
      also examine whether the policy change affected health insurance, health care
      utilization, and arrests. We employ propensity-score methods to address
      differences in observed characteristics between likely substance users and
      others, and we used a difference-in-difference-in-difference approach to mitigate
      potential omitted variables bias. In the short-run (1997-1998), declines in SSI
      receipt accompanied appreciable increases in labor force participation and
      current employment. There was little measurable effect of the policy change on
      insurance and utilization, but we have limited power to detect effects on these
      outcomes. In the later period after the policy change (1999-2002), the rate of
      SSI receipt rose, and short-run gains in labor market outcomes diminished.

PMID- 20138680
TI  - Microinflammation is a common risk factor for progression of nephropathy and
      atherosclerosis in Japanese patients with type 2 diabetes.
AB  - AIM: This study aimed to evaluate the change of serum levels of proinflammatory
      molecules in patients with type 2 diabetes and clarify the involvement of these
      molecules in diabetic nephropathy and atherosclerosis. METHODS: Sixty-six
      Japanese type 2 diabetic patients (T2DM) and 39 healthy control subjects were
      enrolled. We assessed clinical parameters, urinary albumin excretion rate (AER),
      brachial-ankle pulse wave velocity (baPWV), intima media thickness (IMT) and
      serum levels of proinflammatory molecules. RESULTS: Serum levels of IL-6, IP-10
      and MCP-1 were significantly higher in T2DM than in control subjects. In T2DM,
      serum levels of high-sensitivity (hs) CRP, IP-10, hsTNF-alpha, VCAM-1 and E
      selectin were positively correlated with AER. Serum levels of IP-10, hsTNF-alpha
      and VCAM-1 were positively correlated with baPWV. Serum levels of hsCRP, IL-6, IP
      10 and hsTNF-alpha were positively correlated with IMT. Multiple linear
      regression analysis revealed that serum levels of hsTNF-alpha were independently
      associated with AER (beta=0.235, P=0.038) and serum levels of IP-10 were
      independently associated with baPWV (beta=0.209, P=0.047) and IMT (beta=0.303,
      P=0.032). CONCLUSION: Our results suggest that low-grade inflammation,
      microinflammation, may be a common risk factor for diabetic nephropathy and
      atherosclerosis in Japanese type 2 diabetic patients.

PMID- 20138681
TI  - Diabetes Research and Clinical Practice Junior Research Prize: Conference report,
      2009.

PMID- 20138682
TI  - Increased plasma adiponectin closely associates with vascular endothelial
      dysfunction in type 2 diabetic patients with diabetic nephropathy.
AB  - Several studies found that adiponectin, an adipokine withstands atherosclerosis
      in vivo, is significantly increased in subjects with diabetic nephropathy (DN),
      but its clinical meaning remains unclear. For its structural similarity to
      complement C1q and collagen, we performed this study to explore the relationship
      between adiponectin and the vascular endothelial function alterations in DN
      patients. 50 type 2 diabetic patients without clinical cardiovascular
      complications were assigned to control group, microalbuminuria group (Micro-MA),
      and macroalbuminuria group (Macro-MA) according to the Mogensen's criteria.
      Plasma adiponectin and soluble vascular cell adhesion molecule-1 (sVCAM-1) were
      detected. Flow-mediated dilatation (FMD), nitroglycerin-induced dilatation (NID)
      and cardiologic parameters were measured by ultrasound cardiogram. Plasma
      adiponectin level was significantly and gradually increased in agreement with the
      amount of urine albumin excretion. sVCAM-1 was higher in Micro-MA and Macro-MA
      patients than in the controls, but it was comparable between the former 2 groups.
      FMD and NID were both remarkably decreased in Macro-MA group compared with Micro
      MA and control group. For the whole subjects, plasma adiponectin was negatively
      related to FMD (r=-0.397, P<0.01) and NID (r=-0.413, P<0.01). These results
      suggest that increased plasma adiponectin may predict co-existing vascular
      endothelial dysfunction in DN patients.

PMID- 20138683
TI  - Congenital disorders of glycosylation in hepatology: the example of polycystic
      liver disease.
AB  - Autosomal dominant polycystic liver disease (PCLD) is a rare progressive disorder
      characterized by an increased liver volume due to many (>20) fluid-filled cysts
      of biliary origin. Disease causing mutations in PRKCSH or SEC63 are found in
      approximately 25% of the PCLD patients. Both gene products function in the
      endoplasmic reticulum, however, the molecular mechanism behind cyst formation
      remains to be elucidated. As part of the translocon complex, SEC63 plays a role
      in protein import into the ER and is implicated in the export of unfolded
      proteins to the cytoplasm during ER-associated degradation (ERAD). PRKCSH codes
      for the beta-subunit of glucosidase II (hepatocystin), which cleaves two glucose
      residues of Glc(3)Man(9)GlcNAc(2) N-glycans on proteins. Hepatocystin is thereby
      directly involved in the protein folding process by regulating protein binding to
      calnexin/calreticulin in the ER. A separate group of genetic diseases affecting
      protein N-glycosylation in the ER is formed by the congenital disorders of
      glycosylation (CDG). In distinct subtypes of this autosomal recessive multisystem
      disease specific liver symptoms have been reported that overlap with PCLD. Recent
      research revealed novel insights in PCLD disease pathology such as the absence of
      hepatocystin from cyst epithelia indicating a two-hit model for PCLD
      cystogenesis. This opens the way to speculate about a recessive mechanism for
      PCLD pathophysiology and shared molecular pathways between CDG and PCLD. In this
      review we will discuss the clinical-genetic features of PCLD and CDG as well as
      their biochemical pathways with the aim to identify novel directions of research
      into cystogenesis.

PMID- 20138684
TI  - Public policy and the dependency of nursing home residents in Australia: 1968-69
      to 2006-07.
AB  - OBJECTIVE: The purpose of this paper is to derive annual estimates of the
      aggregate dependency of the nursing home population in Australia, and to use
      these data to consider the impact of Government policies to target nursing home
      services to those with high care-needs/dependency. Two related tools, the
      'Aggregate Dependency Value' and 'Aggregate Dependency Index', have been
      constructed using the principles of case-mixed based systems, to quantify the
      aggregate dependency of residents. Data on all residents 1968-1969 to 2006-2007,
      and on newly admitted residents 1992-1993 to 2006-2007 have been derived and
      analysed. METHODS: To construct the tools, the percent of residents classified
      into various dependency categories were weighted by proxy measures of their
      dependency. These were summed, and converted into index numbers to estimate rates
      of change in the aggregate dependency of residents. The derived data were used to
      consider possible impacts of the policies. RESULTS: The data indicate that the
      dependency of residents has, for the most part, increased over recent decades but
      that the rate of the increase has varied. An increase in the dependency of
      residents corresponds with the policies' objectives. CONCLUSIONS: The tools
      extend the ways the dependency of nursing home residents in Australia can be
      assessed. The estimates support the effectiveness of the Government's targeting
      policies but causal relationships have not been estimated.

PMID- 20138685
TI  - Boron deficiency results in induction of pathogenesis-related proteins from the
      PR-10 family during the legume-rhizobia interaction.
AB  - Boron (B) deficiency has a strong effect on molecular and cellular plant-bacteria
      interactions during the development of the legume-rhizobia symbiosis, leading to
      reduced infection and early necrosis of nodules, resembling a pathogenic-like
      rather than a symbiotic interaction. Therefore, induction of pathogenesis-related
      (PRs) proteins was investigated here in legume root nodules. Following two
      dimensional electrophoresis and MALDI-TOF spectrometry analysis of proteins
      extracted from Pisum sativum B-sufficient (+B) or B-deficient (-B) root nodules,
      two proteins from the family PR10, ABR17 and PR10.1, were identified as highly
      induced in -B nodules. Analysis of gene expression and the use of anti-ABR17
      confirmed that induction occurred in B-deficient young nodules and increased
      during nodule development. ABR17 was also induced in -B nodules of Phaseolus
      vulgaris. Boron deficiency did not significantly increase the expression of these
      PR10 in uninfected plant tissues. Moreover, independent of B, induction was
      detected in senescent tissues, although at a level weaker than in -B nodules. The
      immunochemical study of ABR17 antigen distribution showed that it was localized
      in all tissues of poorly invaded B-deficient nodules and accumulated around
      bacteria, which showed advanced degradation. These results suggest that, under B
      deficiency, the rhizobia-legume dialogue fails and the bacterium is recognized as
      a pathogen by the plant, which reacts to prevent infection by inducing at least
      these two identified PR10 proteins.

PMID- 20138686
TI  - Over-expression of superoxide dismutase exhibits lignification of vascular
      structures in Arabidopsis thaliana.
AB  - The present study demonstrated that over-expression of copper-zinc superoxide
      dismutase (Cu/Zn-SOD), an important enzyme scavenging reactive oxygen species,
      improved vascular structures through lignification and imparted tolerance to salt
      stress (NaCl) in Arabidopsis thaliana (Arabidopsis; accession Col-0). Transgenic
      plants of Arabidopsis were developed by over-expressing cytosolic Cu/Zn-SOD from
      Potentilla atrosanguinea under CaMV35S promoter via Agrobacterium tumefaciens
      mediated transformation. Homozygous T(3) lines were analyzed for morphological,
      anatomical and molecular differences in response to salt stress. The transgenic
      plants showed higher germination and survival percentage, larger root length,
      larger rosette area and the higher number of leaves as compared to the wild type
      (WT) under NaCl stress. Anatomical studies of the inflorescence stem revealed
      significant thickening of inter-vesicular cambium in transgenics under NaCl
      stress as compared to the (i) WT and the transgenics raised in the absence of
      NaCl stress, as well as (ii) WT raised under NaCl stress. This thickening was
      possibly due to lignification as evidenced by the confocal microscopy. Also, the
      up-regulation of transcripts of critical genes of lignin biosynthesis,
      phenylalanine ammonia-lyase1 (PAL1) and peroxidase (PRXR9GE) in the transgenics
      supported lignification of vascular tissue under the above stated conditions.
      Results have been discussed on the possible implication of over-expression of
      PaSOD in lignification of vascular structure under NaCl stress in Arabidopsis.

PMID- 20138687
TI  - [MRI in congenital nystagmus].
AB  - INTRODUCTION: Congenital nystagmus (CN) that is present by the age of 3 months is
      the most common form of nystagmus in childhood. We present a prospective study
      (2001-2008) in which we report imaging findings in 48 children with CN. MATERIALS
      AND METHODS: Twenty-six boys and 22 girls with CN underwent a complete
      ophthalmologic assessment and a cerebral MRI (mean age of examination under
      general anesthesia: 11 months). Three CN groups were formed: neurologic (n=27),
      sensory visual disturbance (n=14), and isolated (n=7). Cerebral MRI was
      interpreted by the same pediatric neuroradiologist (NG). Of the children studied,
      98 % were born at term. The MRI abnormalities were classified as morphologic
      abnormalities (malformative or nonmalformative) and as signal abnormalities. The
      location of brain abnormalities was within the posterior fossa, (brain stem,
      cerebellum, dental nuclei, cisterna magna) and the cerebral hemisphere (white
      matter, perivascular spaces, midline commissures, basal ganglia). RESULTS:
      Pendular nystagmus was prevalent in sensory and neurologic nystagmus. On fundus
      examination, optic disc abnormalities were present in 70 % (19) of neurologic CN
      and associated with white matter abnormalities of the optic radiations in 40 % of
      cases. On MRI, malformative morphologic abnormalities were present in 27 cases,
      nonmalformative abnormalities were found in 67, and signal abnormalities in 68.
      Within the brain stem, signal abnormalities were found as a cockade appearance of
      the posterior pons in the reticular regions (neurologic n=14, sensory n=6,
      isolated n=3). Other bright (most frequent) signal abnormalities were found
      within the dentate nuclei of the posterior fossa (neurologic n=10, sensory n=3,
      isolated n=3) and the cerebral white matter (neurologic n=17, sensory n=7,
      isolated n=5) of which 24 (neurologic n=15, sensory n=5, isolated n=4) involved
      the optic radiations. Most of these abnormalities were related and were seen most
      frequently in neurologic nystagmus. The most frequent association was signal
      abnormalities of the white matter, ventricular dilatation, and dilatation of the
      perivascular spaces (60.4 %) (neurologic n=13, sensory n=6). CONCLUSION: This
      study showed the fundamental contribution of the cerebral MRI in CN. Cerebral
      abnormalities were found at the pathways for ocular motility, particularly at the
      saccadic pathways.

PMID- 20138688
TI  - [Real-time PCR for early detection and monitoring of Legionella pneumophila in
      clinical specimens].

PMID- 20138689
TI  - [Utility of a commercial antigenic detection method for diagnosing pandemic
      influenza a (H1N1)].

PMID- 20138690
TI  - Peripheral facial palsy after varicella. Report of two cases and review of the
      literature.
AB  - BACKGROUND: There is little information regarding peripheral facial palsy (PFP)
      as a complication of varicella. We describe 2 adults who developed varicella
      related PFP, in 1 case as a part of Guillain-Barre syndrome (GBS), and review all
      reported cases of this condition. METHODS: MEDLINE search. RESULTS: A total of 10
      cases of isolated varicella-associated PFP have been reported. PFP was diagnosed
      3 to 16 days after the onset of skin manifestations. Four (40%) patients
      developed bilateral PFP. Two patients had varicella meningitis; both were PCR
      positive for varicella-zoster virus (VZV) in CSF. CSF IgG antibodies against VZV
      were demonstrated in 2 other patients. One patient had slight CSF albumino
      cytological dissociation. Five patients were treated with acyclovir, and 3 of
      them also received corticosteroids. Most patients showed a favorable course, with
      partial or complete recovery of PFP. In addition, 17 patients with GBS after the
      onset of varicella were reviewed. Mean time to the development of GBS after
      varicella onset was 9.3 days, and 9 patients had PFP as a part of the neurologic
      picture. Seven patients (41%) developed respiratory failure requiring mechanical
      ventilation. Six patients received treatment with intravenous immunoglobulin, and
      all of them showed optimal evolution. One patient died. CONCLUSIONS: Isolated PFP
      and GBS are rare peripheral nerve complications after varicella. Treatment should
      be individualized for each case, depending on the severity of the condition and
      the clinical evolution.

PMID- 20138691
TI  - [Pleural empyema due to salmonella enteritidis].

PMID- 20138692
TI  - The effects of fasting and refeeding with a 'metabolic preconditioning' drink on
      substrate reserves and mononuclear cell mitochondrial function.
AB  - BACKGROUND AND AIMS: Preoperative fasting induces metabolic stress and leads to
      reduced postoperative insulin sensitivity, changes attenuated by preoperative
      carbohydrate loading. However, the mechanisms underlying these effects remain
      unknown. We investigated the dynamic changes in substrate metabolism and
      mononuclear cell mitochondrial function after fasting followed by refeeding with
      a drink [ONS (Fresenius Kabi, Germany)] designed to improve metabolic function
      preoperatively. METHODS: Twelve healthy volunteers took part in this study. They
      were fed a standardized meal and studied 4h later (baseline 'fed' state), after
      12 and 24h of fasting, and 2, 4 and 6h after ingestion of ONS (contained 100g
      carbohydrate, 30g glutamine, and antioxidants). Changes in liver and muscle
      glycogen and lipids were studied using (13)C and (1)H magnetic resonance
      spectroscopy. The activities of mitochondrial electron transport chain complexes
      I, II and IV in blood mononuclear cells were measured spectrophotometrically.
      RESULTS: Compared to the baseline fed state, 12 and 24h fasts led to 29% and 57%
      decreases (P<0.001) in liver glycogen content, respectively. Fasting for 24h
      decreased mitochondrial membrane complexes I (-72%, P<0.05), II (-49%, P<0.01)
      and IV (-41%, P<0.05) activities compared to those following a 12h fast. A 23%
      increase (P<0.05) in calf intramyocellular lipid (IMCL) content occurred after a
      24h fast. Liver glycogen reserves increased by 47% (P<0.05) by 2h following
      ingestion of ONS. CONCLUSIONS: Short-term fasting (up to 24h) affected
      mononuclear cell mitochondrial function adversely and increased IMCL content.
      Refeeding with ONS partially reversed the changes in liver glycogen.

PMID- 20138693
TI  - Changes in resting energy expenditure and their relationship to insulin
      resistance and weight gain: a longitudinal study in pre-pubertal children
      (EarlyBird 17).
AB  - BACKGROUND & AIMS: In adults, adjustments in resting energy expenditure (REE) are
      used to defend energy balance against disturbance caused by over-and under
      nutrition, and may be linked to changes in insulin resistance and leptin. Little
      is known of these associations in children. Our aim was to test the hypothesis
      that long-term weight gain in children is met with adaptive changes in resting
      energy expenditure, mediated by insulin resistance and/or leptin. METHODS: REE by
      indirect calorimetry, anthropometry, body composition by DEXA, insulin resistance
      (HOMA-IR) and serum leptin were measured annually in 232 children from the age of
      7-10 y. RESULTS: REE rose from 7 to 10 y, and the rise exceeded that predicted by
      the concurrent rise in fat and fat-free mass by 184 kcal/day in the boys and by
      160 kcal/day in the girls. However, there were no significant relationships in
      either gender between this 'excess' rise in REE and change in body composition (r
      < or = 0.08, p > or = 0.42). The rise in both boys and girls was associated with,
      but not explained by, a rise in insulin resistance (p < or = 0.002). There was no
      association with serum leptin (p > or = 0.32). CONCLUSIONS: The data do not
      support the hypothesis of adaptive changes in REE in pre-pubertal children, and
      insulin resistance explains very little of the pre-pubertal rise in REE. The rise
      in REE beyond that explained by changes in body composition may reflect an
      increase in energy requirements prior to puberty.

PMID- 20138695
TI  - Pb isotopes as tracers of mining-related Pb in lichens, seaweed and mussels near
      a former Pb-Zn mine in West Greenland.
AB  - Identification of mining-related contaminants is important in order to assess the
      spreading of contaminants from mining as well as for site remediation purposes.
      This study focuses on lead (Pb) contamination in biota near the abandoned 'Black
      Angel Mine' in West Greenland in the period 1988-2008. Stable Pb isotope ratios
      and total Pb concentrations were determined in lichens, seaweed and mussels as
      well as in marine sediments. The results show that natural background Pb
      ((207)Pb/(206)Pb: 0.704-0.767) and Pb originating from the mine ore
      ((207)Pb/(206)Pb: 0.955) have distinct isotopic fingerprints. Total Pb in
      lichens, seaweed, and mussels was measured at values up to 633, 19 and 1536 mg
      kg(-1) dry weight, respectively, and is shown to be a mixture of natural Pb and
      ore-Pb. This enables quantification of mining-related Pb and shows that
      application of Pb isotope data is a valuable tool for monitoring mining
      pollution.

PMID- 20138696
TI  - [Cardiac tamponade due to a pleuropericardial cyst with invasive lung cancer].
AB  - Pericardial and pleuropericardial cysts are uncommon (7% of all mediastinal
      masses) and in the majority of cases are symptomatic and it is usually a casual
      finding. We present the case of a 62 year-old male with a left-sided
      pleuropericardial cyst which had the development of a cardiac tamponade; a rare
      finding in this type of disease. After it was surgically removed, the
      histopathology showed infiltration of the cyst by a poorly differentiated large
      cell carcinoma.

PMID- 20138697
TI  - [Bronchial atresia together with a gonadal teratoma: what is the relationship?].

PMID- 20138698
TI  - [Peak oxygen uptake during the six-minute walk test in diffuse interstitial lung
      disease and pulmonary hypertension].
AB  - INTRODUCTION: The six-minute walk test (6MWT) is widely used in evaluating
      diffuse interstitial lung disease (ILD) and pulmonary hypertension (PH). However,
      their physiological determining factors have not been well defined. OBJECTIVE: To
      evaluate the physiological changes that occur in ILD and PH during the 6MWT, and
      compare them with the cardiopulmonary exercise test (CPET). MATERIAL AND METHODS:
      Thirteen patients with ILD and 14 with PH were studied using the 6MWT and CPET on
      an ergometer cycle. The respiratory variables were recorded by means of telemetry
      during the 6MWT. RESULTS: Oxygen consumption (VO(2)), respiratory and heart rate
      reached a plateau from minute 3 of the 6MWT in both diseases. The VO(2) did not
      differ from the peak value in the CPET (14+/-2 and 15+/-2 ml/kg/min,
      respectively, in ILD; 16+/-6 and 16+/-6 ml/kg/min, in PH). The arterial oxygen
      saturation decreased in both diseases, although it was more marked in ILD (-12+/
      5%, p<0,01). The ventilatory equivalent for CO(2) (V(E)/VCO(2)) in PH during the
      6MWT was strongly associated with functional class (FC) (85+/-14 in FC III-IV,
      44+/-6 in FC I-II; p<0,001). CONCLUSIONS: The 6MWT in ILD and PH behaves like a
      maximal effort test, with similar VO(2) to the CPET, demonstrating a limit in
      oxygen transport capacity. Monitoring using telemetry during the 6MWT may be
      useful for the clinical evaluation of patients with ILD or PH.

PMID- 20138699
TI  - Polyurethane rotating disc system for post-treatment of anaerobically pre-treated
      sewage.
AB  - The performance of polyurethane rotating discs (RBC-1) versus polystyrene
      rotating discs (RBC-2) for the treatment of an up-flow anaerobic sludge blanket
      (UASB) reactor effluent fed with domestic wastewater was investigated. Both RBC
      units were operated at the same organic loading rate (OLR) of 10.5 gCOD/m(2) d.
      and a hydraulic retention time (HRT) of 2.5 h. The residual values of COD
      fractions (COD(suspended), COD(colloidal) and COD(soluble)) in the treated
      effluent of RBC-1 and RBC-2 were similar. However, the removal efficiency of
      ammonia in the RBC-1 (87 +/- 4%) was significantly higher than that found for RBC
      2 i.e. 24 +/- 6%. Moreover, RBC-1 achieved a substantial removal efficiency of
      99.0 +/- 1% for Escherichia coli (E. coli), while RBC-2 removed 91.2 +/- 0.3%.
      Based on these results, optimization of RBC-1 treating UASB reactor effluent was
      extensively performed. The RBC-1 was operated at an OLR's of 4.0, 11 and 23
      gCOD/m(2) d. The results obtained showed that increasing the OLR from 11.0 to
      23.0 gCOD/m(2) d and decreasing the HRT from 2.5 to 1.25 h significantly declined
      the effluent quality of COD(total) and ammonia. However, the residual values of
      COD(total) and ammonia remained unaffected when increasing the OLR from 4.0 to
      11.0 gCOD/m(2) d and by decreasing the HRT from 5 to 2.5 h. Bacteriological
      examination showed that the mean residual count of E. coli remained at a level of
      10(4)/100 ml, in the effluent of RBC-1 independent on the imposed HRT.
      Accordingly, it is recommended to operate RBC-1 for treatment of anaerobically
      pre-treated sewage at an OLR of 11 gCOD/m(2) d and an HRT of 2.5 h. A feed-less
      (ammonia limitation) period of 9.0 days followed by 9.0 days feeding with high
      OLR of 26 gCOD/m(2) d. (raw sewage) was investigated to elaborate, if the
      nitrifiers of the RBC-1 are capable to convert ammonia to nitrate after totally
      18 days when retuning back to the normal operating conditions. The results of the
      experiment clearly show a strong and immediate detrimental effect of imposing
      high OLR of 26 gCOD/m(2) d on the nitrification process in the nitrifying RBC
      unit. However, after returning back to the original OLR of 10.6 gCOD/m(2) d, the
      nitrification efficiency in the RBC unit was recovered within 2-3 days.

PMID- 20138701
TI  - Effect of protease and cellulase on the characteristic of activated sludge.
AB  - Sludge dewatering is a key part of sludge disposal since it can greatly reduce
      the volume of sludge and thus improve the treatment effect for handling and
      disposing. This study investigated the potential benefits of enzymatic
      pretreatment on activated sludge dewatering with protease and cellulase as a
      protein and polysaccharide degrading enzyme, respectively. Capillary suction time
      (CST) and the solid content after centrifugation were used to evaluate sludge
      dewatering. The particle size distribution, extracellular polymeric substances
      (EPS) content, infra-red (IR) spectrometry and microscope image were determined
      in an attempt to explain the observed changes in sludge dewaterability. The
      results indicated that adding protease and cellulase separately leads to an
      increase in CST and the increased value is higher with protease. Protease and
      cellulase both promote the degradation of protein and polysaccharide in the
      solids of activated sludge, leading to a smaller particle diameter and poorer
      dewaterability. However, due to the limited effects on the protein and
      polysaccharide content, the difference in sludge dewaterability is not large.
      Compared to the control, enzymatic pretreatment had no obvious effect on sludge
      IR spectrometry, while there was a detectable structure difference at a colloidal
      scale.

PMID- 20138703
TI  - Sequence heterogeneity in the gene encoding the rhoptry-associated protein-1 (RAP
      1) of Babesia caballi isolates from South Africa.
AB  - A competitive-inhibition enzyme-linked immunosorbent assay (cELISA) developed for
      the detection of antibody specific for Babesia caballi was used to test sera
      collected from 1237 South African horses. None of these samples tested positive
      using the cELISA, although 63 samples tested positive for B. caballi antibody
      using the indirect fluorescent antibody test (IFAT). We therefore characterized
      the rap-1 gene that codes for the antigen (rhoptry-associated protein, RAP-1)
      used in the cELISA, from South African B. caballi isolates. Three sets of primers
      were designed to amplify the complete gene and flanking regions (approximately
      1800 bp), but only one set of primers yielded PCR products, and we were only able
      to amplify a region at the 5' end of the gene (615 bp) from ten South African B.
      caballiin vitro-cultured isolates. Sequence data from seven of these were
      obtained. The sequences showed between 79% and 81% identity to B. caballirap-1
      gene sequences that have been reported in the literature (accession numbers:
      AF092736 and AB017700). The GenomeWalker Universal kit (Clonetech) was used to
      amplify the regions flanking the 615bp B. caballirap-1 fragment from two South
      African isolates. Amplified products were cloned into the pGEM-T Easy vector and
      sequenced. The complete rap-1 gene sequence, comprising a single open reading
      frame of 1479 bp that encodes a protein consisting of 493 amino acids, was
      obtained from the two South African isolates. This sequence data was used to
      redesign the amplification primers and rap-1 homologues were obtained from a
      further eight isolates. BLASTP analysis indicated an amino acid identity of
      between 57.9% and 65.1% to the two RAP-1 protein sequences, AF092736 and
      AB017700, with most differences occurring at the carboxy-terminus. The amino acid
      sequence differences probably explain why it was not possible to detect B.
      caballi antibody in IFAT positive sera from South Africa using the cELISA.
      Redesigning the current cELISA using a conserved epitope of the RAP-1 antigen, or
      a more conserved protein as the target antigen, may overcome this problem.

PMID- 20138704
TI  - Effect of Lysimachia ramosa (Primulaceae) on helminth parasites: motility,
      mortality and scanning electron microscopic observations on surface topography.
AB  - The alcoholic extract of Lysimachia ramosa Wall (Primulaceae) was tested in vitro
      against helminth parasites, Fasciolopsis buski and Ascaris suum, from porcine
      hosts and Raillietina echinobothrida from domestic fowl. The live adult
      parasites, collected from a freshly autopsied host, were exposed to different
      concentrations (5-50mg) of the test plant extract in physiological phosphate
      buffered saline (PBS) having 0.1% dimethyl sulphoxide (DMSO) at 37+/-1 degrees C.
      The treated parasites revealed complete inactivation and flaccid paralysis that
      was followed by death at varying periods of time. A dose-dependent loss of
      motility and mortality was observed in all the treated parasites. Scanning
      electron microscopic observations revealed conspicuous deformity of the surface
      architecture in all the parasites exposed to the test plant extract. The general
      tegument in F. buski showed shrinkage and loss of scale-like spines; proglottides
      all along the strobilar length in R. echinobothrida appeared shrunken and
      deformed and the cuticular surface of A. suum appeared disorganised, having lost
      transverse striations. The botanicals of the test plant seem to be effective
      against all the three types of helminth parasites.

PMID- 20138705
TI  - Molecular characterisation of Cryptosporidium isolates from Swedish dairy cattle
      in relation to age, diarrhoea and region.
AB  - Cryptosporidium positive samples from 176 preweaned calves, young stock and cows
      of 48 herds were subjected to molecular characterisation of the 18S rRNA gene to
      determine which species are present in Swedish dairy cattle. In addition, samples
      characterised as Cryptosporidium parvum were further analysed at the GP60 gene to
      investigate distribution and zoonotic potential of subtypes. The 18S rRNA gene
      was successfully sequenced in 110 samples, with Cryptosporidium bovis in 83, C.
      parvum in 15, Cryptosporidium ryanae in 10, and Cryptosporidium andersoni in two
      samples. C. bovis was the most common species, being identified in 74% of calf
      samples, in 77% of young stock samples and in 100% of cow samples. The youngest
      calves infected with C. bovis were 7 days old, showing that the prepatent period
      is shorter than the previously stated 10 days. C. parvum was detected in 15
      calves from nine farms, and samples were clustered in the southern parts of
      Sweden. Diarrhoeic calf samples contained C. parvum, C. bovis or C. ryanae.
      Sequencing of the GP60 gene was successful in 13 of the C. parvum samples. Eight
      subtypes, including three novel ones, were detected. Four of the subtypes have
      previously been identified in humans. This indicates that there is a zoonotic
      potential in C. parvum infected Swedish dairy calves.

PMID- 20138706
TI  - Toxocara vitulorum in beef calves in North Central Florida.
AB  - In this study, we evaluated the prevalence of Toxocara vitulorum in beef calves
      in North Central Florida. Fecal samples from 433 calves under 9 months of age
      were analyzed for the presence of eggs in their feces. The prevalence in calves
      less than 3 months of age was 17.6%, 3-4 months of age was 0.4% and those 5-6
      months old had a 0.9% prevalence. As expected, no eggs were detected in any
      calves older than 6 months. Calves were treated with fenbendazole (10% FBZ) at
      5mg/kg after fecal samples were collected. Twenty calves that had T. vitulorum
      eggs in the feces were resampled 2 weeks after treatment to evaluate
      effectiveness of FBZ. No T. vitulorum eggs were seen in the feces of 17/20 (85%)
      of the calves that were sampled after FBZ treatment. FBZ was effective in 85% of
      calves treated for T. vitulorum infection in calves. We would like to make beef
      ranchers and veterinarians in the southern states aware that the prevalence of
      this parasite has greatly increased recently in northern Florida beef units.

PMID- 20138707
TI  - Molecular interaction between arsenic hydrate microcrystals and the cell-surface
      endopeptidase CD10 (neprilysin) - a possible link to the development of renal and
      cutaneous malignancies upon occupational exposure to arsenic compounds?
AB  - Arsenic poisoning has become a worldwide public health concern since arsenic is
      recognized as a human carcinogen although the detailed mechanisms of
      carcinogenesis related to arsenic exposure are not completely understood at
      present. In particular, the skin and the kidneys are prone to neoplastic
      transformation upon occupational exposure of the human body to inorganic arsenic
      compounds. The cell-surface endopeptidase CD10 is variably expressed in cutaneous
      and renal malignancies, and due to this expression profile, might theoretically
      be implicated in arsenic-induced skin and renal neoplasias. From the functional
      point of view, CD10 conveys important anti-tumorigenic effects brought about by
      the inactivation of neuropeptide growth factors implicated in cancer progression.
      Placing the focus on the structural composition of arsenic hydrate microcrystals
      encountered in the cellular microenvironment, the present hypothesis suggests so
      far neglected molecular interactions between arsenic microcrystals and membrane
      bound CD10 to be implicated in arsenic-induced carcinogenesis.

PMID- 20138708
TI  - Asymmetric testicular levels in the crotch: authors' reply.

PMID- 20138709
TI  - From benign prostatic hyperplasia to benign chronic prostatopathy.

PMID- 20138710
TI  - HPV status in head and neck tumors.
AB  - HPV infection has been associated with head and neck carcinoma (HNSCC). In the
      present study, a tumor collective from Middle Germany was analyzed using two HPV
      detection methods, i.e., PCR followed by agarose gel electrophoresis and
      microarray chip hybridization. In addition, the predictive value of tumor
      morphology was assessed. In total, 76 HNSCCs from 52 patients were examined,
      including 23 pairs of primaries and corresponding metastases. The highest rate of
      positive tumors was observed in the tonsils, with 76% of the patients and 81% of
      tumor samples being positive for high-risk HPV. DNA chip analysis detected
      significantly more HPV-positive cases than did agarose gel electrophoresis.
      Except for one HPV-33-positive case, all others tumors harbored HPV 16. There was
      a good concordance between the HPV status of the primary tumor and its
      corresponding metastasis (21/23 cases, 91%). In two cases, HPV was found only in
      the primary tumor but not in the metastasis. Our results clearly confirmed the
      high prevalence of HR-HPV in tonsillar carcinomas with a rate that was even 20%
      higher than those reported in the literature. Morphology is a valuable indicator
      for an HPV association that needs to be confirmed by molecular tests.

PMID- 20138711
TI  - Correction of the typical cleft hand.
AB  - The correction of type II and III typical cleft hands can be complicated because
      each hand can contain a variation of congenital problems including syndactyly,
      camptodactyly, thumb hypoplasia, deficiency of the first web space, abnormal
      phalanges, maligned joints, and abnormal intrinsic muscles and extrinsic tendons.
      The most difficult problem is the index ray, which lies in a "no man's land"
      between the central cleft and the mobile thumb. Presented in this paper is a
      technique for correction and transposition of the index ray through a simple
      incision, which separates the glabrous from the dorsal skin surfaces. Skeletal
      alignment must be precise. Preservation of the adductor pollicis muscle, if
      present, is crucial to a functional pinch. Long-term problems such as persistent
      radial deviation of the index finger and unyielding flexion contractures can be
      avoided.

PMID- 20138712
TI  - Responsiveness of the Michigan Hand Outcomes Questionnaire and the Disabilities
      of the Arm, Shoulder, and Hand questionnaire in patients with hand injury.
AB  - PURPOSE: To compare responsiveness of the Michigan Hand Outcomes Questionnaire
      (MHQ) with that of the Disabilities of the Arm, Shoulder, and Hand (DASH)
      questionnaire in patients with hand injuries. We postulated that the MHQ may be
      more sensitive to functional changes in the hands, whereas the DASH questionnaire
      would have a closer association with days of disability. METHODS: Patients with
      hand injuries were consecutively recruited from 2 community hospitals. Each
      patient was asked to complete out the MHQ, the DASH questionnaire, the
      satisfaction with their health-related quality of life (Sat-HRQOL) measure, and
      Chinese Health Questionnaire (CHQ), which is a measure of psychological
      stressors. Disability days were defined as the duration of restricted activities
      of daily living during the previous 4 weeks. Patients repeated the same
      questionnaires between 2 and 9 months after enrollment (average: 4 mo). RESULTS:
      A total of 105 patients with hand injuries were recruited, and 50 of the 105
      patients returned for the second evaluation. There were no statistical
      differences between responders and nonresponders for age, gender, disability
      days, the MHQ, the DASH questionnaire, the CHQ, or the Sat-HRQOL. Responsiveness
      was evaluated by effect sizes and standardized response means: Those for the MHQ
      were 0.84 and 1.05, and those for the DASH were 0.67 and 0.86, respectively. A
      mixed model analysis for repeated measurements of the 50 participants showed a
      significant influence of psychological factors (CHQ) for both the Sat-HRQOL and
      disability days. After adjustment for the effects of age, gender, and the CHQ,
      there was an increment of one Sat-HRQOL unit for an MHQ score increment of 3.2,
      whereas the score decrement for the DASH questionnaire was 3.3 units.
      CONCLUSIONS: The MHQ might be slightly more sensitive to functional changes, but
      the DASH questionnaire seemed more correlated with disability days. Psychological
      factors are the strongest determinants of the HRQOL and disability.

PMID- 20138713
TI  - Reconstruction of the hypoplastic thumb.
AB  - Thumb hypoplasia is characterized by diminished thumb size, metacarpal adduction,
      metacarpophalangeal joint instability, thenar muscle hypoplasia or aplasia,
      extrinsic tendon dysplasia, and in the most severe cases, carpometacarpal joint
      instability or thumb aplasia. Severe thumb hypoplasia and aplasia are best
      treated by thumb ablation and pollicization of the index finger. Less severe
      thumb hypoplasia can be reconstructed by a combination of soft tissue release,
      first web space local flap coverage, metacarpophalangeal joint collateral
      ligament and capsule reconstruction, extrinsic tendon tenolysis, and muscle or
      tendon transfers.

PMID- 20138714
TI  - Treatment of acute peripheral nerve injuries: current concepts.
AB  - Although clinical outcomes of peripheral nerve injuries are often suboptimal, an
      adherence to well-established basic principles of evaluation and repair can
      optimize results of even the most complex injuries. Proper assessment of injury
      patterns both preoperatively and intraoperatively can guide treatment, and
      multiple repair techniques including strategies for overcoming both small and
      large gaps offer different advantages and disadvantages. New technologies and
      ideas address some unsolved problems, but more experience and research is
      necessary to elucidate fully their roles in the treatment algorithm.

PMID- 20138715
TI  - Acellular dermal regeneration template for soft tissue reconstruction of the
      digits.
AB  - PURPOSE: Trauma to the digits often leaves soft tissue defects with exposed bone,
      joint, and/or tendon that require soft tissue replacement. The objective of this
      study was to evaluate the effectiveness of acellular dermal regeneration template
      combined with full-thickness skin grafting for soft tissue reconstruction in
      digital injuries with soft tissue defects. METHODS: Acellular dermal regeneration
      template was used to reconstruct digital injuries with exposed bone, joint,
      tendon, and/or hardware not amenable to treatment with healing by secondary
      intention, rotation flaps, or primary skin grafts. Acellular dermal regeneration
      template was applied to 21 digits in 17 patients. Nineteen digits had exposed
      bone, 8 digits had exposed tendon, 6 digits had exposed joints, and 2 digits had
      exposed hardware. The acellular dermal regeneration template was sutured over the
      soft tissue defect. Over 3 weeks, a neodermis formed. The superficial silicone
      layer of the acellular dermal regeneration template was removed, and the digits
      received full-thickness epidermal autografting with cotton bolster. RESULTS: The
      duration of postoperative follow-up extended to a minimum of 12 months. For the
      injury sites where acellular dermal regeneration template was applied, the total
      area of application ranged from 1 cm(2) to 24 cm(2), with the largest individual
      site measuring 12 cm(2). Twenty of 21 digits demonstrated 100% incorporation of
      the acellular dermal regeneration template skin substitute. One digit that had
      sustained multilevel trauma developed necrosis requiring revision amputation.
      Full-thickness epidermal autografting was performed an average of 24 days after
      acellular dermal regeneration template skin substitute application and
      demonstrated a 100% take in 16 of 20 digits and partial graft loss of 15% to 25%
      in 4 of 20 digits that did not require further treatment. CONCLUSIONS: Acellular
      dermal regeneration template combined with secondary full-thickness skin grafting
      is an effective method of skin reconstruction in complex digital injuries with
      soft tissue defects involving exposed bone, tendon, and joint. The neodermis
      increases tissue bulk and facilitates epidermal autografting with digital
      injuries that otherwise would require flap coverage or skeletal shortening of the
      digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 20138716
TI  - Comparison of functional outcome after volar plate fixation with 2.4-mm titanium
      versus 3.5-mm stainless-steel plate for extra-articular fracture of distal
      radius.
AB  - PURPOSE: Open reduction and locked volar plate and screw fixation is a popular
      treatment method for extra-articular distal radius fractures with dorsal
      metaphyseal comminution. In this study, we compared the use of a titanium 2.4-mm
      precontoured plate with that of a stainless-steel oblique 3.5-mm T-shaped plate
      to test the null hypothesis that there would be no difference in wrist function
      or upper extremity-specific health status in the internal fixation of AO-type
      A3.2 distal radius fractures. METHODS: We retrospectively analyzed 24 patients
      treated with a 2.4-mm titanium plate and 38 patients treated with a 3.5-mm
      stainless-steel plate for an extra-articular and dorsally angulated distal radius
      fracture, from data gathered in a prospective cohort study of plate and screw
      fixation of distal radius fractures. The 2 cohorts were analyzed for differences
      in motion, grip strength, pain, Gartland and Werley score, Disabilities of the
      Arm, Shoulder, and Hand score, and Short Form-36 score at 6, 12, and 24 months of
      follow-up. Group differences and their change over time were determined using
      regression analysis and the likelihood ratio test. RESULTS: There were no
      significant differences in wrist function and arm-specific health status between
      patients treated with a 2.4-mm plate and those treated with a 3.5-mm plate at 6,
      12, or 24 months of follow-up. However, we observed a trend toward greater wrist
      flexion at 1 year (66 degrees vs 55 degrees ; p=.07) and greater flexion
      extension arc (137 degrees vs 123 degrees ; p=.08) and pronation-supination arc
      (172 degrees vs 160 degrees ; p=.07) at 24 months after surgery in patients
      treated with a 2.4-mm plate. CONCLUSIONS: Patients with a dorsally angulated
      extra-articular distal radius facture can expect similar results when treated
      with either a precontoured 2.4-mm titanium plate or a 3.5-mm stainless-steel T
      shaped plate. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 20138717
TI  - A time-course study of gene responses of chicken granulosa cells to Salmonella
      Enteritidis infection.
AB  - Consumption of eggs contaminated with Salmonella Enteritidis (SE) has been
      recognized as one of the important causes of human foodborne salmonellosis.
      Chicken granulosa cells (cGCs) comprise the last tissue layer surrounding the
      yolk in preovulatory follicles and are a preferred site for SE invasion. To
      understand the cGC response to SE infection, we conducted an in vitro time-course
      study to identify cGC transcriptional changes using chicken whole genome
      microarrays. The expression of 135 (4h postinfection) and 120 cGC genes (48 h
      postinfection) were altered (P<.01) compared to uninfected cells. Many of the
      altered genes were related to immune response, physiological processes, signal
      transduction, and transcription. Furthermore, we also found that the Jak-STAT
      pathway, which is essential in the regulation of cellular cytokines and growth
      factors, was highly active in this study. Among the genes identified by
      microarray, the mRNA levels of TLR15, IL-6, CXCLi1, CXCLi2, and K203 were shown
      to be upregulated by real-time RT-PCR (qRT-PCR). In contrast, the mRNA levels of
      RASD1 and HB-EGF decreased according to both microarray and qRT-PCR analyses.
      These results suggest that during the SE infection, cGCs recruit cells of the
      innate immune responses; the infection may also induce suppression of cGC cell
      proliferation, which alters follicular development and ovulation.

PMID- 20138718
TI  - Lactoferrin and prevention of late-onset sepsis in the pre-term neonates.
AB  - Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in
      neonatal intensive care units (NICUs) worldwide, with high morbidity and related
      mortality, and frequent occurrence of severe late neurodevelopmental impairment.
      Due to the frequency, severity and difficulties in early diagnosis and prompt
      therapy, prevention is crucial for decreasing the burden of infection-related
      complications in NICUs. It is well known that feeding with fresh maternal milk,
      hygiene measures and the cautious use of H2-blockers are related with a decreased
      risk of developing sepsis. However, evidence from randomised clinical trials
      exists only for fluconazole in the prevention of fungal infections in the NICU.
      Lactoferrin is the main whey protein in mammalian milk, and is involved in innate
      immune host defences. Notably, human lactoferrin can be found at increased
      concentrations in colostrum and in milk from mothers of premature neonates. Human
      (hLF) and bovine lactoferrin (bLF) share a high (77%) amino-acid homology, and
      the same N-terminal peptide responsible for antimicrobial activity, called
      lactoferricin. In vitro, bLF shows potent direct antimicrobial activity against
      all types of pathogens, which occurs via anti-cell wall actions and leads to
      disintegration of the micro-organism's membranes. bLF is also synergistic with
      many antimicrobials and antifungals, and promotes growth and differentiation of
      the immature gut. Based on this background data, a randomised clinical trial was
      recently conducted in very low birth weight pre-term neonates given bLF alone or
      with the probiotic Lactobacillus GG. The aim of the trial was to assess the
      ability of bLF to prevent late-onset sepsis of any origin in the studied infants
      during their stay in the NICU. This article discusses the preliminary data from
      this study, along with the proposed mechanisms of action of bLF in pre-term
      infants.

PMID- 20138719
TI  - Male breast cancer: an update in diagnosis, treatment and molecular profiling.
AB  - Significant advances have been made in the diagnosis and treatment of female
      breast cancer, resulting in a decline in incidence and a global improvement in
      clinical outcome. The statistics for male breast cancer (MBC) stand in sharp
      contrast-over the past several decades, there has been a steady rise in the
      incidence of this disease, and clinical outcome has improved at a much slower
      pace. In the current review, the clinicopathologic features of MBC are described
      in detail. An emphasis is placed on molecular profiling of MBC, which may
      identify candidate biomarkers and putative targets for pharmacologic
      intervention. The current role of cytotoxic chemotherapy and endocrine therapy
      (including tamoxifen, aromatase inhibitors and GnRH analogues) is defined in the
      context of currently available studies. Furthermore, the potential role of
      targeted agents, including HER2-directed therapies, PARP inhibitors, and
      angiogenesis inhibitors, is delineated.

PMID- 20138720
TI  - Levocabastine nasal spray significantly improves perennial allergic rhinitis: a
      single-blind placebo-controlled study.
AB  - OBJECTIVE: The efficacy of levocabastine nasal spray for relieving the symptoms
      of perennial allergic rhinitis was compared with placebo in a single-blind study.
      METHODS: Three hundred and thirty-five patients with moderate to severe perennial
      allergic rhinitis were randomized to three groups that were administered a high
      or low dose of levocabastine nasal spray or a placebo. Patients were not informed
      of their treatment. Efficacy was evaluated based on the changes of symptoms and
      rhinoscopy findings. RESULTS: Significant improvement of symptoms was observed in
      both the high-dose and low-dose levocabastine groups compared with the placebo
      group. There were no significant differences of efficacy between the high-dose
      and low-dose levocabastine groups. There was also no significant difference in
      the occurrence of adverse effects among the three groups. CONCLUSION:
      Levocabastine nasal spray is a safe and effective treatment for perennial
      allergic rhinitis.

PMID- 20138721
TI  - Diagnostic utility of DTI in prostate cancer.
AB  - PURPOSE: The aim of this study was to compare the diffusion tensor parameters of
      prostate cancer, prostatitis and normal prostate tissue. MATERIALS AND METHODS: A
      total of 25 patients with the suspicion of prostate cancer were included in the
      study. MRI was performed with 3 T system (Intera Achieva, Philips Medical
      Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each
      subject. TRUS-guided prostate biopsy was performed after the MRI examination.
      Images were analyzed by two radiologists using a special software system. ROI's
      were drawn according to biopsy zones which are apex, midgland, base and central
      zone on each sides of the gland. FA and ADC values in areas of cancer, chronic
      prostatitis and normal prostate tissue were compared using Student's t-test.
      RESULTS: Histopathological analysis revealed carcinoma in 68, chronic prostatitis
      in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was
      significantly higher (p<0.01) than the FA of chronic prostatitis and normal
      gland. The mean ADC of cancerous tissue was found to be significantly lower
      (p<0.01), compared with non-cancerous tissue. CONCLUSION: Decreased ADC and
      increased FA are compatible with the hypercellular nature of prostate tumors.
      These differences may increase the accuracy of MRI in the detection of carcinoma
      and to differentiate between cancer and prostatitis.

PMID- 20138722
TI  - Colour Doppler ultrasonography evaluation of vascularization in the wrist and
      finger joints in rheumatoid arthritis patients and healthy subjects.
AB  - OBJECTIVES: To evaluate the presence of blood flow by colour Doppler
      ultrasonography (CDUS) in the wrist and finger joints of rheumatoid arthritis
      (RA) patients and healthy subjects and to define a cut-off value of CDUS
      resistive index (RI). METHODS: Forty-three patients with RA and 43 healthy
      controls were examined by CDUS. The wrists, second and third metacarpophalangeal
      (MCP) and proximal interphalangeal (PIP) joints were evaluated in each patient
      and healthy subject. Spectral Doppler analysis was performed in order to
      characterize the type of flow and a mean RI was measured to define a cut-off
      level. The area under receiver operating characteristic curve was used to
      evaluate the screening method's performance. RESULTS: Flow was detected in 219 of
      the 430 total joints (50.9%) of RA patients (111 in the wrists, 49 in the MCP and
      30 in the PIP joints). Healthy subjects had a quantifiable flow in 45 of the 430
      joints (10.5%) and, in particular, 39 (86.4%) in the wrist, 5 (11.14%) in the MCP
      and 1 (2.2%) in the PIP joints. The intra- and inter-reader agreements for the
      detection of Doppler signal were very good (kappa 0.82 and 0.89, respectively).
      Mean RI values were 0.72+/-0.06 in RA patients and 0.86+/-0.06 in healthy
      subjects (p<0.01). At cut-off point of RI<0.79 the sensitivity was 89.6% and the
      specificity was 78.8% (positive likelihood ratio 4.22). CONCLUSION: DUS is a
      useful tool for the detection of abnormal blood flow in inflammatory joints of RA
      patients.

PMID- 20138723
TI  - High-resolution cartilage imaging of the knee at 3T: basic evaluation of modern
      isotropic 3D MR-sequences.
AB  - PURPOSE: To evaluate qualitative and quantitative image quality parameters of
      isotropic three-dimensional (3D) cartilage-imaging magnetic resonance (MR)
      sequences at 3T. MATERIALS AND METHODS: The knees of 10 healthy volunteers (mean
      age, 24.4+/-5.6 years) were scanned at a 3T MR scanner with water-excited 3D Fast
      Low Angle Shot (FLASH), True Fast Imaging with Steady-state Precession
      (TrueFISP), Sampling Perfection with Application-optimized Contrast using
      different flip-angle Evolutions (SPACE) as well as conventional and two
      individually weighted Double-Echo Steady-State (DESS) sequences. The MR images
      were evaluated qualitatively and quantitatively (signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR), SNR efficiency, CNR efficiency). Quantitative
      parameters were compared by means of a Tukey-test and sequences were ranked
      according to SNR/CNR, SNR/CNR efficiency and qualitative image grading. RESULTS:
      The highest SNR was measured for SPACE (34.0+/-5.6), the highest CNR/CNR
      efficiency (cartilage/fluid) for the individually weighted DESS (46.9+/
      18.0/2.18+/-0.84). SPACE, individually weighted and conventional DESS were ranked
      best with respect to SNR/CNR and SNR/CNR efficiency. The DESS sequences also
      performed best in the qualitative evaluation. TrueFISP performed worse, FLASH
      worst. The individually weighted DESS sequences were generally better than the
      conventional DESS with the significant increase of cartilage-fluid contrast
      (46.9+/-18.0/31.9+/-11.4 versus 22.0+/-7.3) as main advantage. CONCLUSION:
      Individually weighted DESS is the most promising candidate; all tested sequences
      performed better than FLASH.

PMID- 20138724
TI  - Pain and functional outcome after vertebroplasty and kyphoplasty. A comparative
      study.
AB  - PURPOSE: The aim of this study was to compare the effectiveness of percutaneous
      vertebroplasty and kyphoplasty to treat pain from non-neoplastic vertebral
      fractures and improve functional outcomes. MATERIALS AND METHODS: We compared 30
      patients treated by vertebroplasty for non-neoplastic vertebral fractures with 30
      patients treated by kyphoplasty for the same condition. Pain was measured with a
      visual analogue scale (VAS) and functional outcome with the Oswestry disability
      index (ODI). Baseline data were compared with measurements on the day after the
      procedure (for pain alone) and at 1 month, 6 months, and 1 year. RESULTS: The VAS
      pain score was reduced by 4-5 points on the day after either type of treatment, a
      statistically significant improvement. The global ODI was significantly improved
      (by 13-18 points) at 1 month after either procedure. These improvements persisted
      at 6 months and 1 year. No significant differences in functional outcome were
      observed between the techniques. CONCLUSION: Vertebroplasty and kyphoplasty
      obtain similar improvements in pain and functional outcomes in these patients.
      The choice of technique must therefore depend on other factors. An initial
      improvement with either technique is a good predictor of long-term improvement.

PMID- 20138725
TI  - Clarification letter. Re: Intra- and interobserver reliability of MRI examination
      of intervertebral disc abnormalities in patients with cervical myelopathy.

PMID- 20138726
TI  - Combinative method using HPLC fingerprint and quantitative analyses for quality
      consistency evaluation of an herbal medicinal preparation produced by different
      manufacturers.
AB  - A combinative method using HPLC-DAD fingerprint and quantitative analysis was
      developed and validated for manufacturer-to-manufacturer quality consistency
      evaluation of Yiqing preparations. For fingerprint analysis, 22 peaks were
      selected as the characteristic peaks to evaluate the similarities of different
      samples collected from different manufacturers. The similarities of 12 Yiqing
      samples were beyond 0.90, indicating that samples from different manufacturers
      were, to some extent, consistent. Additionally, simultaneous quantification of
      nine markers including berberine, aloe-emodin, rhein, emodin, chrysophanol,
      baicalin, baicalein, wogonoside, and wogonin in Yiqing was performed to interpret
      the quality consistency. The results from the quantitative data showed that the
      contents of these nine marker compounds were quite consistent for batches
      produced within one manufacturer and significantly different from manufacturer-to
      manufacturer. This study demonstrated that a combination of the chromatographic
      fingerprint and quantitative analysis offers an efficient way to quality
      consistency evaluation of herbal preparation.

PMID- 20138727
TI  - Development and validation of a HPLC method for the determination of sertraline
      and three non-chiral related impurities.
AB  - In this study, a screening on reversed-phase stationary phases (including C(8),
      C(18), CN, PEG and amide) was carried out in order to obtain an efficient HPLC
      method for the determination of sertraline and three of its more closely related
      synthetical and non-chiral impurities, without using ion-pair reagents. The best
      results in terms of both retention time and resolution of the target analytes
      were obtained with a Zorbax Bonus-RP column, which contains a polar amide group
      embedded in a C(14) alkyl chain. Once the most suitable stationary phase was
      chosen, the HPLC method was optimized by using a factorial design, evaluating
      three quantitative factors (column temperature, buffer pH and buffer
      concentration) in order to find the best conditions which maximize the resolution
      between impurities A and B (positional isomers) and minimize the total run time.
      The final HPLC conditions were set by means of a second experimental design,
      which allowed optimizing the effects of the buffer pH and the proportion of
      methanol in the mobile phase. The optimal conditions for simultaneously
      determining sertraline and its impurities, being baseline separated in less than
      10 min, were finally obtained with Zorbax Bonus-RP column (150 mmx4.6mm, 5
      microm), under isocratic conditions with phosphate buffer (pH 2.8; 10mM)-methanol
      (63:37, v/v) at 50 degrees C, at the flow-rate of 1.0 mL/min. UV detection was
      set at 220 nm. This method was successfully validated following ICH guidelines
      and it proved to be reliable for the determination of sertraline and related
      impurities in tablets as pharmaceutical forms.

PMID- 20138728
TI  - Renal parenchymal preservation after percutaneous renal angioplasty and stenting.
AB  - BACKGROUND: The intent of endovascular therapy for symptomatic atherosclerotic
      renal artery stenosis (ARAS) is to preserve parenchyma and avoid renal-related
      morbidity. The aim of this study is to examine the impact of renal artery
      intervention on parenchymal preservation. METHODS: We performed a retrospective
      analysis of records from patients who underwent endovascular intervention for
      ARAS and were followed by duplex ultrasound between 1990 and 2008. Renal volume
      (in cm(3)) was estimated in all patients as renal length (cm) x renal width (cm)
      x renal depth (cm) x 0.5. The normal renal volume was calculated as 2 x body
      weight (kg) in cm(3). Failure of preservation was considered to be a persistent
      10% decrease in volume. Clinical benefit defined as freedom from renal-related
      morbidity (increase in persistent creatinine >20% of baseline, progression to
      hemodialysis, death from renal-related causes) was calculated. RESULTS: Five
      hundred ninety-two renal artery interventions were performed. One hundred eighty
      six kidneys suffered parenchymal loss (>5%) with an actuarial parenchymal loss
      rate of 29% +/- 1% at five years respectively. There were no significant
      differences in age, gender, starting renal volume, or kidney size. However,
      patients with parenchymal loss had lower eGFR (45 +/- 24 vs 53 +/- 24 mL/min/1.73
      m(2); Loss vs noLoss, P = .0002, Mean +/- SD) higher resistive index (0.75 +/-
      0.9 vs 0.73 +/- 0.10; P = .0001) and worse nephrosclerosis grade (1.43 +/- 0.55
      vs 1.30 +/- 0.49; P = .006) then those not suffering parenchymal loss.
      Parenchymal loss was associated with significantly worse five-year survival (26%
      +/- 4% vs 48% +/- 2%; Loss vs noLoss; P < .001) and freedom from renal-related
      morbidity (70% +/- 5% vs 82% +/- 2%; P < .05) with increased numbers progressing
      to dialysis (17% vs 7%; P < .006). CONCLUSION: While parenchymal preservation
      occurs in most patients, parenchymal loss occurs in 31% of patients and is
      associated with markers of impaired parenchymal perfusion (resistive index and
      nephrosclerosis grade) at the time of intervention. Pre-existing renal size or
      volumes were not predictive of parenchymal loss. Parenchymal loss is associated
      with a significant decrease in survival and a marked increased renal related
      morbidity and progression to hemodialysis.

PMID- 20138730
TI  - Entrapment of the popliteal artery.

PMID- 20138731
TI  - A retrospective multicenter study of endovascular treatment of popliteal artery
      aneurysm.
AB  - PURPOSE: To evaluate the feasibility of endovascular exclusion of popliteal
      artery aneurysm (PAA) using stent grafts. METHODS: The clinical data of all
      patients who underwent endovascular exclusion of PAA at three French vascular
      departments between December 1999 and December 2007 were retrospectively
      analyzed. Outcome measures included graft patency and endoleak. The Kaplan-Meier
      method was used to calculate the primary and secondary patency curves. RESULTS: A
      total of 57 PAA in 50 patients (48 men; mean age, 72 +/- 11 years; range, 57-96
      years) were treated. The type of stent graft used was Hemobahn/Viabahn in 42
      (73.7%) cases, Wallgraft in 14 (24.5%) and Passager in one. The mean duration of
      hospitalization was 5 +/- 1.8 days (range, 3-11 days). No patients were lost from
      follow up (mean, 36 +/- 19.4 months; range, 6-96 months). Nine (16%) occlusions
      and six (10.5%) endoleaks occurred. The global limb salvage rate was 96.5% (55 of
      57 PAA). Kaplan-Meier estimates for primary and secondary patency were 85.8% and
      87.5% at one year and 82.3% and 87.5% at three years. CONCLUSIONS: Endovascular
      treatment of PAA is feasible in selected patients. The main determinants of
      success are suitable aneurysm anatomy and dual antiplatelet postoperative
      therapy. Further studies are warranted to determine long-term outcomes of
      endovascular repair for PAA.

PMID- 20138732
TI  - Obstructed small bowel ruptured toward the inguinal canal resulting from
      metastatic colon carcinoma in an irreducible, recurrent inguinal hernia with mesh
      plug repair: Report of a case.
AB  - Four years after treatment of colon cancer an 82-year-old man presented with an
      irreducible, recurrent inguinal hernia with mesh-plug repair. Delayed surgical
      exploration revealed metastatic cancer with small bowel adhesion to the mesh-plug
      and perforation. The mesh-plug with adherent tissue was removed through the
      inguinal incision, and the ruptured small bowel was resected. Histopathology
      revealed moderately differentiated mucinous adenocarcinoma of the tissue adhering
      to the prosthetic material corresponding to the original colon cancer.

PMID- 20138733
TI  - [Flexible laryngeal mask airway use during surgical burn management with head
      mobilisation: a feasibility study].
AB  - OBJECTIVE: To evaluate the feasibility and reliability of the flexible laryngeal
      mask airway (LMA flexible) use during scalp skin harvesting for surgical
      reparation of burn sequella. STUDY DESIGN: Observational prospective descriptive
      study. PATIENTS AND METHODS: Following local ethic committee approval, 26
      patients were included in the study during their preanaesthesia visit. The
      general anaesthesia induction of each patient was followed by the insertion of a
      LMA flexible. The number of attempts required to insert the mask and the
      procedure were documented. The oropharyngeal leak pressure, expired tidal volume
      and end tidal CO(2) were recorded in five different head positions (neutral,
      hyperflexion, hyperextension, right and left rotation) at the start and end of
      surgical procedure. In all ten study periods of 2-3 min each were evaluated.
      RESULTS: The airway device was inserted easily in all patients. While similar in
      four of the five head positions (neutral: 27.9+/-8.1 cmH(2)O, hyperextension,
      left and right rotation), the oropharyngeal leak pressure was significantly
      higher in the hyperflexion position (33.3+/-7.3 cmH(2)O). The end tidal volume
      was stable in all positions except hyperflexion (419+/-114 ml). While this value
      was significantly lower than the 471+/-68 ml recorded in the neutral position, it
      remained greater than 7 ml/kg. No significant change was observed for end tidal
      CO(2) for the ten study periods. CONCLUSION: The use of LMA flexible during
      surgical burn repair procedures, including head mobilisation for the harvesting
      of scalp skin grafts is feasible.

PMID- 20138734
TI  - New study on neural networks: the essential order of approximation.
AB  - For the nearly exponential type of feedforward neural networks (neFNNs), the
      essential order of their approximation is revealed. It is proven that for any
      continuous function defined on a compact set of R(d), there exist three layers of
      neFNNs with the fixed number of hidden neurons that attain the essential order.
      Under certain assumption on the neFNNs, the ideal upper bound and lower bound
      estimations on approximation precision of the neFNNs are provided. The obtained
      results not only characterize the intrinsic property of approximation of the
      neFNNs, but also proclaim the implicit relationship between the precision (speed)
      and the number of hidden neurons of the neFNNs.

PMID- 20138735
TI  - Implication of the CD47 pathway in autoimmune diabetes.
AB  - CD47 and signal regulatory protein (SIRP) interactions have been proposed to take
      part in autoimmune disease susceptibility. Importantly, a recent genome-wide
      association study for type 1 diabetes susceptibility highlighted the association
      of the 20p13 region comprising the SIRP cluster, where some of the SIRP proteins
      encode functional ligands to CD47. Using a TCR transgenic mouse model at the
      brink of autoimmune disease, we demonstrate that CD47-deficiency is sufficient to
      break the immune tolerance and provoke the onset of autoimmune diabetes.
      Interestingly, CD47-deficient mice show a severe reduction in the number of
      mature CD4(-)CD8(-) T cells, and passive transfer of these CD4(-)CD8(-) T cells
      is sufficient to restore immune tolerance and prevent diabetes progression.
      Together, these findings constitute an in vivo demonstration that CD47 is
      involved in diabetes susceptibility and controls the homeostatic regulation of
      CD4(-)CD8(-) T cells.

PMID- 20138736
TI  - EEG spindles in the rat: evidence for a synchronous network phenomenon.
AB  - Whether physiological and pathological electroencephalographic (EEG) spindling
      phenomena are generated by similar mechanisms remains unknown. We studied four
      different types of spindling events analysing the behaviour of 19 brain regions
      during these events in the intact brain of freely behaving rats hypothesising
      similar generation with a leading role of thalamus or cortex for the dominant
      rhythm of the spindles with a hierarchy of time delays for propagation throughout
      the brain led by these structures. Autoregressive analysis revealed that all
      structures studied were capable of leading a spindle, although some did so
      infrequently. The highest incidence of significant leadership was shown by
      hindlimb cortex with a proportion of 0.38 during picrotoxin spindles.
      Contralateral time delays within bilateral structures were extremely small
      demonstrating synchronous activity with no dominant hemisphere for any of the
      spindling activities (range: 0.1+/-0.4 ms for frontal cortex to 10.0+/-1.6 ms for
      piriform cortex). Between different structures, time delays demonstrated that
      spindling activity occurred in all structures almost simultaneously (range: 0.2+/
      1.4 ms between frontal cortex and piriform cortex to 12.3+/-1.2 ms between
      hindlimb cortex and amygdala). We conclude that different spindle types appear to
      be subtle alterations of a single phenomenon, during which many brain regions
      briefly synchronise.

PMID- 20138737
TI  - Antiepileptogenic and anticonvulsive actions of levetiracetam in a
      pentylenetetrazole kindling model.
AB  - Levetiracetam (LEV) is a unique antiepileptic drug that preferentially interacts
      with synaptic vesicle protein 2A (SV2A). To evaluate the antiepileptogenic action
      of LEV, we studied its effects on the development and acquisition of
      pentylenetetrazole (PTZ) kindling and compared them to those of sodium valproate
      (VPA). Anticonvulsive actions of LEV in PTZ-kindled animals were also determined.
      LEV did not affect PTZ seizures in naive animals even at high doses
      (approximately 300 mg/kg, i.p.). However, combined treatment of LEV (30 and 100
      mg/kg, i.p.) with PTZ significantly suppressed the development and acquisition of
      PTZ kindling. In addition, LEV at relatively low doses (3-30 mg/kg, i.p.)
      inhibited PTZ-evoked seizures in fully kindled animals. In contrast to LEV, VPA
      at sub-anticonvulsive doses (30 and 100 mg/kg, i.p.) failed to prevent the
      development of PTZ kindling and its anticonvulsive potency was similar in PTZ
      kindled and naive mice. The present study shows that LEV contrasts VPA by
      preventing the development of PTZ kindling and inhibiting seizures selectively in
      kindled animals.

PMID- 20138738
TI  - Psychopathology, social adjustment and personality correlates of schizotypy
      clusters in a large nonclinical sample.
AB  - INTRODUCTION: Correlational methods, unlike cluster analyses, cannot take into
      account the possibility that individuals score highly on more than one symptom
      dimension simultaneously. This may account for some of the inconsistency found in
      the literature of correlates of schizotypy dimensions. This study explored the
      clustering of positive and negative schizotypy dimensions in nonclinical subjects
      and whether schizotypy clusters have meaningful patterns of adjustment in terms
      of psychopathology, social functioning, and personality. METHODS: Positive and
      negative schizotypy dimensional scores were derived from the Chapman Psychosis
      Proneness Scales for 6137 college students and submitted to cluster analysis. Of
      these, 780 completed the NEO-PI-R and Social Adjustment Scale-self report
      version, and a further 430 were interviewed for schizophrenia-spectrum, mood, and
      substance use psychopathology. RESULTS: Four clusters were obtained: low
      (nonschizotypic), high positive, high negative, and mixed (high positive and
      negative) schizotypy. The positive schizotypy cluster presented high rates of
      psychotic-like experiences, schizotypal and paranoid symptoms, had affective and
      substance abuse pathology, and was open to experience and extraverted. The
      negative schizotypy cluster had high rates of negative and schizoid symptoms,
      impaired social adjustment, high conscientiousness and low agreeableness. The
      mixed cluster was the most deviant on almost all aspects. CONCLUSIONS: Our
      cluster solution is consistent with the limited cluster analytic studies reported
      in schizotypy and schizophrenia, indicating that meaningful profiles of
      schizotypy features can be detected in nonclinical populations. The clusters
      identified displayed a distinct and meaningful pattern of correlates in different
      domains, thus providing construct validity to the schizotypy types defined.

PMID- 20138739
TI  - Grey matter changes associated with host genetic variation and exposure to Herpes
      Simplex Virus 1 (HSV1) in first episode schizophrenia.
AB  - BACKGROUND: We previously reported reduced prefrontal cortex (PFC) grey matter
      volume among first episode, antipsychotic-naive schizophrenia subjects (SZ)
      exposed to HSV1 but not among healthy subjects (HS) (Prasad et al., 2007).
      Independently, rs1051788, an exonic polymorphism of the MHC Class I polypeptide
      related sequence B (MICB) gene was associated with HSV1 seropositivity, as well
      as SZ risk. In this study, we examined whether PFC grey matter changes associated
      with HSV1 exposure varied against the background of MICB genotypes. METHODS: We
      examined Caucasian individuals from the sample we studied in our previous report
      (Prasad et al., 2007) (SZ, n=21 and HS, n=19). Whole brain voxelwise analysis of
      structural MRI scans was conducted using Statistical Parametric Mapping, ver 5
      (SPM5). The impact of rs1051788 variation and HSV1 seropositivity on grey matter
      volumes was examined using regression models on the combined sample of cases and
      controls, and then within each diagnostic group. RESULTS: In the combined sample
      of cases and controls, we observed the main effects of HSV1 seropositivity and
      genotypes, and a significant joint effect of HSV1 seropositivity and genotype
      mainly in the PFC. The joint effect was more prominent among cases than among
      controls. DISCUSSION: Our observations suggest that rs1051788 and HSV1
      seropositivity are associated individually and jointly with reduced PFC grey
      matter volume. The patterns of these associations differ by diagnostic status,
      and these factors explain only a "small" portion of the variance in the grey
      matter volume reductions.

PMID- 20138740
TI  - Susceptibility to five antifungals of Aspergillus fumigatus strains isolated from
      chronically colonised cystic fibrosis patients receiving azole therapy.
AB  - Exposure of Aspergillus fumigatus to stressful antifungal therapies may result in
      decreased susceptibility. The aim of the present work was to evaluate the
      susceptibility to azole and non-azole antifungals of 159 isolates of A. fumigatus
      collected from cystic fibrosis (CF) patients receiving azole antifungal therapy.
      The genetic diversity of the fungal isolates was assessed using microsatellite
      genotyping, and some strains were found in patient's sputum samples more than 4
      years apart. No resistant isolates [minimal inhibitory concentration
      (MIC)/minimal effective concentration (MEC)>or=4 microg/mL] were identified to
      the antifungals amphotericin B, caspofungin, itraconazole and voriconazole. A
      single A. fumigatus isolate was identified outside of the epidemiological cut-off
      of 0.25 microg/mL for posaconazole. Susceptibility of the recurrent isolates was
      in agreement with the susceptibility of the first isolate identified (100%
      essential agreement). Even after azole exposure, several recurrent A. fumigatus
      strains were detected in the subsequent sputum samples. Development of resistance
      in A. fumigatus to antifungals appears to be rare amongst CF patients. However,
      it remains crucial to evaluate the importance of antifungal agents for allergic
      fungal diseases.

PMID- 20138741
TI  - Mechanisms of resistance to ciprofloxacin, ampicillin/sulbactam and imipenem in
      Acinetobacter baumannii clinical isolates in Taiwan.
AB  - Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii
      have been increasing in recent years, posing a threat to public health worldwide.
      The susceptibility to eight antimicrobial agents of 35 clinical A. baumannii
      isolates from Taiwan was tested. Isolates were examined by polymerase chain
      reaction (PCR) and sequencing for beta-lactamase genes and mutations in the gyrA
      and parC genes. Expression of AdeB, an efflux pump protein, was evaluated by real
      time quantitative PCR. The level of adeB expression correlated with resistance to
      ciprofloxacin and ampicillin/sulbactam in A. baumannii isolates. Almost all
      isolates with full resistance to ciprofloxacin had both high adeB expression and
      point mutations in parC and gyrA, but 4 intermediate-resistant isolates had only
      high adeB expression without point mutations in gyrA or parC, in contrast to 18
      susceptible isolates with low adeB expression and without mutations in gyrA or
      parC. Sixteen isolates (45.7%) carrying a type 1 integron were MDR as well as
      being more resistant to imipenem, amikacin, gentamicin, ceftazidime or cefepime
      than those without the integron. The class 1 integron in A. baumannii carried
      different resistance gene cassettes, including 5'CS-bla(IMP-1)-aadA4-3'CS, 5'CS
      aacA4-aadA1-3'CS and 5'CS-aacC1-aadA1-3'CS. In conclusion, expression of the adeB
      gene was associated with resistance to ciprofloxacin and ampicillin/sulbactam in
      A. baumannii. Multiple mutations in gyrA and parC also played a role in
      ciprofloxacin resistance. The major metallo-beta-lactamase contributing to
      imipenem resistance in A. baumannii in Taiwan was bla(IMP-1), which was carried
      by the class 1 integron. The class 1 integron was associated with the MDR
      phenotype in A. baumannii.

PMID- 20138742
TI  - [A rare cause of dyspnea in children: the pulmonary alveolar microlithiasis].

PMID- 20138743
TI  - Effects on antioxidant status of liver following atrazine exposure and its
      attenuation by vitamin E.
AB  - In the present investigation, the effect of atrazine on antioxidant enzymes and
      body weight was studied in male Wistar rats. Atrazine (300 mg/kgbw) was
      administered by gavage for 7, 14 and 21 days. A significant increase in hepatic
      lipid peroxidation (LPO) was observed following atrazine administration. Vitamin
      E treatment (100 mg/kgbw), on the otherhand, attenuated atrazine-induced LPO in
      liver. In addition, vitamin E treatment restored the GSH content and glucose-6
      phosophate dehydrogenase activity that was found to be lowered after atrazine
      administration. The activities of antioxidant enzymes: superoxide dismutase,
      catalase, glutathione peroxidase and glutathione-s-transferase were significantly
      increased following atrazine administration and vitamin E treatment could restore
      these activities. In conclusion, the results of the study demonstrate that
      atrazine induces oxidative stress in terms of enhanced lipid peroxidation.
      However, vitamin E treatment ameliorated the effects of atrazine suggesting it as
      potential antioxidant against atrazine-induced oxidative stress.

PMID- 20138744
TI  - Intoxication by Senna occidentalis seeds in pregnant goats: prenatal and
      postnatal evaluation.
AB  - Senna occidentalis is a weed toxic to different animal species. Very little is
      known about the effects of prolonged exposure to low doses of S. occidentalis on
      developmental toxicology. Thus, the present study proposes an approach to
      evaluate the perinatal toxicity of S. occidentalis seeds in goats. Twenty-one
      pregnant goats were fed rations containing 0% (control), 1% (So1 group), 2% (So2
      group) and 4% (So4 group) mature S. occidentalis seeds from pregnancy detection
      on day 27 after mating until parturition; weight gains and serum biochemistry
      were evaluated. Fetuses were evaluated using ultrasonographic measurements;
      neonates were evaluated by body morphometry, weight gains, and serum
      biochemistry. Fetal resorption occurred in 2 So4 dams and one dam died. Only a
      few minor alterations in serum biochemistry occurred in dams and kids; even so
      one So4 group dam had tissue lesions as vacuolations in hepatocytes and kidneys;
      necrosis in skeletal and cardiac muscles and for the first time lesions were
      observed in sciatic nerve cells. No relevant alterations in body morphometry were
      observed. This study suggests that 4% S. occidentalis seeds is toxic for pregnant
      goats, but levels of seeds less than 4% have little impact on fetal and post
      birth body development.

PMID- 20138745
TI  - Female genital morphology and mating behavior of Orchestina (Arachnida: Araneae:
      Oonopidae).
AB  - The unusual reproductive biology of many spider species makes them compelling
      targets for evolutionary investigations. Mating behavior studies combined with
      genital morphological investigations help to understand complex spider
      reproductive systems and explain their function in the context of sexual
      selection. Oonopidae are a diverse spider family comprising a variety of species
      with complex internal female genitalia. Data on oonopid phylogeny are preliminary
      and especially studies on their mating behavior are very rare. The present
      investigation reports on the copulatory behavior of an Orchestina species for the
      first time. The female genitalia are described by means of serial semi-thin
      sections and scanning electron microscopy. Females of Orchestina sp. mate with
      multiple males. On average, copulations last between 15.4 and 23.54min. During
      copulation, the spiders are in a position taken by most theraphosids and certain
      members of the subfamily Oonopinae: the male pushes the female back and is
      situated under her facing the female's sternum. Males of Orchestina sp. possibly
      display post-copulatory mate-guarding behavior. The female genitalia are complex.
      The genital opening leads into the uterus externus from which a single
      receptaculum emerges. The dorsal wall of the receptaculum forms a sclerite
      serving as muscle attachment. A sclerotized plate with attached muscles lies in
      the posterior wall of the uterus externus. The plate might be used to lock the
      uterus during copulation. The present study gives no direct evidence for cryptic
      female choice in Orchestina sp. but suggests that sexual selection occurs in the
      form of sperm competition through sperm mixing.

PMID- 20138746
TI  - TaqIB polymorphism in the CETP gene modulates the impact of HC/LF diet on the HDL
      profile in healthy Chinese young adults.
AB  - The aim of this study was to investigate the interactions of genetic variants in
      the genes of cholesterol ester transfer protein (CETP) and low-density
      lipoprotein receptor (LDLR) with high carbohydrate and low fat (HC/LF) diet on
      lipid profiles in a young and healthy Chinese Han population. Fifty-six healthy
      subjects (22.89+/-1.80 years) were given washout diets of 31% fat and 54%
      carbohydrate for 7 days, followed by HC/LF diets of 15% fat and 70% carbohydrate
      for 6 days, with no total energy restriction. Serum lipid profiles at baseline,
      after washout and following HC/LF diets, as well as CETP and LDLR polymorphisms
      were analyzed. Carriers of B2 allele of CETP TaqIB polymorphism had significantly
      higher levels of high density lipoprotein cholesterol (HDL-C) and apo A-I in the
      whole study population after the diet intervention. Notably, males with CETP
      TaqIB B1B1 experienced significantly increased HDL-C and apo A-I after HC/LF
      diet. Regarding the LDLR Pvu II polymorphism, both P1P1 subjects and P2 carriers
      experienced decreased total cholesterol (TC) and low-density lipoprotein
      cholesterol (LDL-C) levels after HC/LF diet with no statistically significant
      differences between the genotypes. Our results demonstrate that the elevated HDL
      C levels after HC/LF diet in healthy Chinese Han youth are associated with CETP
      TaqI B2 allele while males with B1B1 genotype are more susceptible to the
      influence of HC/LF diet on their HDL-C levels. The decreased TC and LDL-C levels
      after HC/LF diet are not associated with LDLR Pvu II polymorphism.

PMID- 20138747
TI  - Longitudinal trajectories of ketamine use among young injection drug users.
AB  - BACKGROUND: Ketamine is a dissociative anaesthetic that became increasingly
      popular in the club and rave scene in the 1980s and 1990s. Reports surfaced in
      the late 1990s indicating that ketamine was being injected in several U.S. cities
      by young injection drug users (IDUs). Since all studies on ketamine injection
      were cross-sectional, a longitudinal study was undertaken in 2005 to determine:
      characteristics of young IDUs who continue to inject ketamine; frequency of
      ketamine injection over an extended time period; risks associated with ongoing
      ketamine injection; and environmental factors that impact patterns of ketamine
      use. METHODS: Young IDUs aged 16-29 with a history of injecting ketamine (n=101)
      were recruited from public locations in Los Angeles and followed during a 2-year
      longitudinal study. A semi-structured instrument captured quantitative and
      qualitative data on patterns of ketamine injection and other drug use. A
      statistical model sorted IDUs who completed three or more interviews (n=66) into
      three groups based upon patterns of ketamine injection at baseline and follow-up.
      Qualitative analysis focused on detailed case studies within each group. RESULTS:
      IDUs recruited at baseline were typically in their early 20s, male, heterosexual,
      white, and homeless. Longitudinal injection trajectories included: "Moderates,"
      who injected ketamine several times per year (n=5); "Occasionals," who injected
      ketamine approximately once per year (n=21); and "Abstainers," who did not inject
      any ketamine during follow-up (n=40). Findings suggest that ketamine is
      infrequently injected compared to other drugs such as heroin, cocaine, and
      methamphetamine. Most IDUs who begin injecting ketamine will stop or curb use due
      to: negative or ambivalent experiences associated with ketamine; an inability to
      find the drug due to declining supply; or maturing out of injecting drugs more
      generally. CONCLUSION: Reducing ketamine injection among young IDUs may best be
      accomplished by targeting particular groups of IDUs identified in this study,
      such as homeless youth and homeless travellers.

PMID- 20138748
TI  - Siting MSW landfill using weighted linear combination and analytical hierarchy
      process (AHP) methodology in GIS environment (case study: Karaj).
AB  - Selection of landfill site is a complex process and needs many diverse criteria.
      The purpose of this paper is to evaluate the suitability of the studied site as
      landfill for MSW in Karaj. Using weighted linear combination (WLC) method and
      spatial cluster analysis (SCA), suitable sites for allocation of landfill for a
      20-year period were identified. For analyzing spatial auto-correlation of the
      land suitability map layer (LSML), Maron's I was used. Finally, using the
      analytical hierarchy process (AHP), the most preferred alternative for the
      landfill siting was identified. Main advantages of AHP are: relative ease of
      handling multiple criteria, easy to understand and effective handling of both
      qualitative and quantitative data. As a result, 6% of the study area is suitable
      for landfill siting and third alternative was identified as the most preferred
      for siting MSW landfill by AHP. The ranking of alternatives were obtained only by
      applying the WLC approach showed different results from the AHP. The WLC should
      be used only for the identification of alternatives and the AHP is used for
      prioritization. We suggest the employed procedure for other similar regions.

PMID- 20138749
TI  - Visual detection of sub-femtomole DNA by a gold nanoparticle seeded homogeneous
      reduction assay: toward a generalized sensitivity-enhancing strategy.
AB  - Gold nanoparticles (AuNPs) have been employed to design colorimetric visual
      sensing assays toward the detections of various targets including DNA, based on
      the aggregation induced color transitions of AuNPs. However, the relatively high
      detection limit (LOD 10nM) in the case of DNA detection has become a stumbling
      block on the road of the further development and applications of these assays.
      This research aims at overcoming this limit by virtue of a seeded gold reduction
      strategy. Typically, low concentrations of 13 nm AuNPs modified with suitable DNA
      probes are allowed to hybridize with a DNA target to form aggregates, which are
      then transferred into a gold-enhancing cocktail for further depositions of more
      gold on the initial AuNP seeds. The color of the assay thus sensitively reflects
      the initial aggregation status of the 13 nm AuNPs, which can be related to the
      concentrations of the DNA target. This assay has a sensitivity that is at least
      25-50 times improved. Under still not fully optimized conditions, 0.4 fmol DNA in
      a 2 microL sample can be confidently detected with the ability of distinguishing
      a single base mutation. It does not require isolations of the 13 nm AuNP
      aggregates during analyses and shares the advantages of a homogeneous assay,
      including simplicity, adaptability, convenience, and being free of interferences
      due to non-specific surface adsorptions.

PMID- 20138750
TI  - Colorimetric biosensing of mercury(II) ion using unmodified gold nanoparticle
      probes and thrombin-binding aptamer.
AB  - A colorimetric assay for the determination of mercury(II) (Hg2+) in the presence
      of lead(II) (Pb2+) was demonstrated with unmodified gold nanoparticles (AuNPs) as
      probes and 15-mer thrombin-binding aptamer (TBA, 5'-GGTTGGTGTGGTTGG-3') as
      sensing elements. Upon the addition of Hg2+ or Pb2+, TBA consisting of six
      thymidine units and nine guanosine units interacted specifically with both ions
      to form a hairpin-like or a quadruplex structure, respectively. As a result,
      these conformation changes facilitated the salt-induced AuNP aggregation.
      Subsequently, to eliminate Pb2+ interference in the determination of Hg2+, a
      novel technique by the use of a characteristic wavelength of aggregated AuNPs
      instead of the universal masking agent of Pb2+ (2,6-pyridinedicarboxylic acid,
      PDCA) was herein proposed. A comparison of the absorption spectra of the
      aggregated AuNPs in the presence of Hg2+ and Pb2+ showed that the characteristic
      wavelength of the aggregated AuNPs (800 nm) facilitated the determination of Hg2+
      in the presence of Pb2+. The calibration curve showed that the absorbance value
      at 800 nm increased linearly over the Hg2+ concentration range of 0.39-8.89
      microM with a limit of detection of 200 nM. Then, the assay was successfully
      employed to determine Hg2+ in several water samples.

PMID- 20138751
TI  - Data integration and analysis of biological networks.
AB  - During the past decade, bottom-up and top-down approaches of network
      reconstruction have greatly facilitated integration and analysis of biological
      networks, including transcriptional, protein interaction, and metabolic networks.
      As increasing amounts of multidimensional high-throughput data become available,
      biological networks have also been upgraded, allowing more accurate understanding
      of whole cellular characteristics. The network size is constantly expanding as
      larger volume of information and omics data are further integrated into the
      biological networks previously built upon a single type of data. Such effort more
      recently led to the modeling of human metabolic network and prediction of its
      tissue-specific metabolism, reconstruction of consensus yeast metabolic network,
      and simulation of mutual interactions among multiple microorganisms. It is
      expected that this trend will continue, the outcomes of which will allow
      development of more sophisticated networks integrating diverse omics data, and
      enhance our understanding of biological systems.

PMID- 20138752
TI  - The tricks learnt by human enteric pathogens from phytopathogens to persist
      within the plant environment.
AB  - Through recent advances in our understanding of microbial:plant interactions it
      is becoming apparent that human pathogens, principally, Escherichia coli O157:H7
      and Salmonella are adapted to survive in the plant environment. The
      aforementioned pathogens have surface epitopes that can bind to plant structures
      such as stomata to aid attachment. In addition, Salmonella is attracted and able
      to metabolize nutrients contained within the apoplastic fluid of plants. The
      question of internalization into the inner tissue of plants remains inconclusive
      largely because of the problems encountered in detecting low pathogen levels.
      Nevertheless, once internalized human pathogens can trigger and potentially evade
      plant defenses that are typically induced by phytopathogens. Although more
      research in this area is required, the hypothesis that human pathogens have
      adapted to the plant environment as part of their natural lifecycle appears to be
      supported.

PMID- 20138754
TI  - Nutrient recovery from the dry grind process using sequential micro and
      ultrafiltration of thin stillage.
AB  - The effectiveness of microfiltration (MF) and ultrafiltration (UF) for nutrient
      recovery from a thin stillage stream was determined. When a stainless steel MF
      membrane (0.1microm pore size) was used, the content of solids increased from
      7.0% to 22.8% with a mean permeate flux rate of 45L/m(2)/h (LMH), fat increased
      and ash content decreased. UF experiments were conducted in batch mode under
      constant temperature and flow rate conditions. Permeate flux profiles were
      evaluated for regenerated cellulose membranes (YM1, YM10 and YM100) with
      molecular weight cut offs of 1, 10 and 100kDa. UF increased total solids, protein
      and fat and decreased ash in retentate stream. When permeate streams from MF were
      subjected to UF, retentate total solids concentrations similar to those of
      commercial syrup (23-28.8%) were obtained. YM100 had the highest percent permeate
      flux decline (70% of initial flux) followed by YM10 and YM1 membranes. Sequential
      filtration improved permeate flux rates of the YM100 membrane (32.6-73.4LMH) but
      the percent decline was also highest in a sequential MF+YM100 system. Protein
      recovery was the highest in YM1 retentate. Removal of solids, protein and fat
      from thin stillage may generate a permeate stream that may improve water removal
      efficiency and increase water recycling.

PMID- 20138753
TI  - From circuits to behaviour: motor networks in vertebrates.
AB  - Neural networks in the hindbrain and spinal cord generate the simple patterns of
      motor activity that are necessary for breathing and locomotion. These networks
      function autonomously, producing simple yet flexible rhythmic motor behaviours
      that are highly responsive to sensory inputs and central control. This review
      outlines recent advances in our understanding of the genetic programmes
      controlling the assembly and functioning of circuits in the hindbrain and spinal
      cord that are responsible for respiration and locomotion. In addition, we
      highlight the influence that target-derived retrograde signaling and experience
      dependent mechanisms have on establishing connectivity, particularly with respect
      to sensory afferent innervation of the spinal cord.

PMID- 20138755
TI  - The removal of nitrogen and phosphorus from reject water of municipal wastewater
      treatment plant using ferric and nitrate bioreductions.
AB  - Reject water, which is the liquid fraction produced after dewatering of
      anaerobically digested activated sludge on the municipal wastewater treatment
      plants (MWWTPs), contributes up to 80% of the nitrogen and phosphorus loads to
      the MWWTP. It was proposed to combine the removal of nitrogen from reject water
      using the sequential biooxidation of NH(4)(+) and bioreduction of NO(3)(-) with
      precipitation of phosphate by Fe(2+) ions produced due to bioreduction of Fe(3+)
      in iron ore. Bioreduction of NO(3)(-) decreased Fe(3+) bioreduction rate in
      reject water from 37 to 21mg Fe(2+)/Ld due to competition between NO(3)(-) and
      Fe(3+) for electron donors. Addition of acetate as electron donor increased both
      bioreduction rates of Fe(3+) and NO(3)(-) but acetate interfered with the
      competition between nitrate and phosphate anions reacting with ferrous cations
      decreasing efficiency of the phosphate removal from reject water. The stages of
      denitrification and ferric bioreduction/phosphate precipitation must be performed
      sequentially.

PMID- 20138756
TI  - A new approach to the biobleaching of flax pulp with laccase using natural
      mediators.
AB  - The phenols syringaldehyde (SA), acetosyringone (AS) and p-coumaric acid (PCA)
      were used as natural laccase mediators in combination with a laccase from
      Pycnoporus cinnabarinus to bleach flax fibres. Their performance was compared
      with 1-hydroxybenzotriazole (HBT) in terms of enzyme stability, and pulp and
      effluent properties. HBT and PCA were found to inactivate laccase in the absence
      of pulp. However, in the presence of unbleached flax pulp stability was
      increased; for example with PCA, laccase retained 77% of its initial activity, in
      contrast with complete inactivation in the absence of pulp. This suggests a
      protective effect of the pulp against denaturalization of the enzyme. All natural
      mediators resulted in a reduced kappa number after the subsequent alkaline
      treatment with hydrogen peroxide; the reduction being especially marked with SA
      (about 2 units - with respect to the control sample) and comparable to that
      obtained by HBT. Brightness was significantly increased by all natural mediators,
      but especially by AS and SA (23% with both), which performed very similarly to
      HBT in this respect. Natural mediators therefore might constitute an effective
      alternative to synthetic mediators for flax pulp biobleaching. This paper
      demonstrates for the first time the use of natural mediators in the laccase
      assisted delignification of flax pulp and their effect on the properties of the
      resulting effluents.

PMID- 20138757
TI  - Biogas and CH(4) productivity by co-digesting swine manure with three crop
      residues as an external carbon source.
AB  - Co-digesting swine manure with three agricultural residues, i.e., corn stalks,
      oat straw, and wheat straw, to enhance biogas productivity was investigated in
      this study. A 3x3 experimental design with duplicates was adopted (3 crop
      residuesx3 carbon/nitrogen ratios) to examine the improvement of batch digestion
      in terms of biogas volume produced, CH(4) content in the biogas, and net CH(4)
      volume. The crop residues were first cut into small sections and then ground into
      fine particles smaller than 40 mesh size (0.422mm) before being added to
      digesters. All the digesters were run simultaneously under controlled temperature
      at 37+/-0.1 degrees C. The length of experiment was 25days. The results showed
      that all crop residues significantly increased biogas production and net CH(4)
      volume at all C/N ratios, among which corn stalks performed the best with
      increase in daily maximum biogas volume by 11.4-fold as compared to the control,
      followed by oat straw (8.45-fold) and wheat straw (6.12-fold) at the C/N ratio of
      20/1, which was found to be the optimal C/N ratio for co-digestion in the present
      study. In addition, corn stalks achieved the highest CH(4) content in the biogas
      ( approximately 68%), which was about 11% higher than that of oat straw (
      approximately 57%), whereas wheat straw and the control both had produced biogas
      with approximately 47% CH(4) content. Wheat straw demonstrated a lower biogas
      productivity than corn stalks and oat straw even it had a higher carbon content
      (46%) than the latter two residues (39%).

PMID- 20138758
TI  - Nitrous oxide emission from nitrifying activated sludge dependent on
      denitrification by ammonia-oxidizing bacteria.
AB  - Nitrous oxide (N(2)O) is emitted during the aerated nitrification process of
      wastewater treatment, but its mechanism is not understood. In this study, we
      employed a model system to clarify the mechanism of N(2)O emission, utilizing the
      activated sludge derived from a piggery effluent. Aerated incubation of the
      sludge with ammonium (NH(4)(+)) or hydroxylamine (NH(2)OH) resulted in the
      emission of a significant amount of N(2)O. The emission stopped when the
      nitrification substrate (NH(4)(+) or NH(2)OH) was exhausted. When NH(4)(+) was
      replaced with nitrate (NO(3)(-)) and nitrite (NO(2)(-)), no N(2)O was emitted.
      This result suggests that the N(2)O emission under nitrifying conditions did not
      depend on the oxidation of NO(2)(-) by nitrite-oxidizing bacteria (NOB) or
      denitrification by heterotrophic denitrifiers but depended on the oxidation of
      NH(4)(+) by ammonia-oxidizing bacteria (AOB). When NO(2)(-), the product of
      nitrification by AOB, was added to the NH(4)(+)-oxidizing system, N(2)O emission
      was enormously enhanced, suggesting that N(2)O was formed via denitrification.
      Diethyldithiocarbamate (DCD), an inhibitor of copper-containing nitrite reductase
      (NirK), strongly blocked N(2)O emission from NH(2)OH. Furthermore, the expression
      of the gene (nirK) encoding NirK of AOB was detected in the sludge exposed to the
      nitrifying conditions. The results showed that N(2)O emission during the
      nitrification process depends on denitrification by AOB that reside in the
      activated sludge. This study provides direct evidence for the cause of N(2)O
      emission from activated sludge (non-pure culture).

PMID- 20138759
TI  - Structure-activity relationships of bacterial outer-membrane permeabilizers based
      on polymyxin B heptapeptides.
AB  - A series of cationic cyclic heptapeptides based on polymyxin B have been
      synthesized for use as permeabilizers of the outer membrane of Gram-negative
      bacteria. Only analogs with the Dab(2)-d-Phe(3)-Leu(4)-Xxx(5) sequence (Xxx = Dab
      or Orn) showed a synergistic bactericidal effect when combined with conventional
      antibiotics, indicating that the Dab(2) residue plays a critical role in
      permeation of the outer membrane of Gram-negative bacteria.

PMID- 20138760
TI  - Novel 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one derivatives as potential
      anti-cancer agents.
AB  - A novel series of 3,5,6-trisubstituted pyrazolo[4,3-d]pyrimidin-7-one
      derivatives, especially 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-ones were
      synthesized and evaluated for their in vitro anticancer activities against
      various human cancer cell lines. The inhibitory activities for several kinases
      have also been tested. The prepared compounds library exhibited significant
      anticancer activity towards HT-29 colon and DU-145 prostate cancer cell lines.
      The structure-activity relationships of the 6-N-arylcarboxamidopyrazolo[4,3
      d]pyrimidin-7-one scaffold at R(1), R(2) and R(3) have been elucidated. Among the
      synthesized compounds, 12b was the most active compound with GI(50) value of
      0.44microM and 1.07microM against HT-29 and DU-145 cell lines, respectively, and
      13a was the most selective compound towards colon cancer cell line.

PMID- 20138761
TI  - Part 2: Structure-activity relationship (SAR) investigations of fused pyrazoles
      as potent, selective and orally available inhibitors of p38alpha mitogen
      activated protein kinase.
AB  - A novel class of pyrazolopyridazine p38alpha mitogen-activated protein kinase
      (MAPK) inhibitors is disclosed. A structure activity relationship (SAR)
      investigation was conducted driven by the ability of these compounds to inhibit
      the p38alpha enzyme, the secretion of TNFalpha in a LPS-challenged THP1 cell line
      and TNFalpha-induced production of IL-8 in the presence of 50% human whole blood
      (hWB). This study resulted in the discovery of several inhibitors with IC(50)
      values in the single-digit nanomolar range in hWB. Further investigation of the
      pharmacokinetic profiles of these lead compounds led to the identification of
      three potent and orally bioavailable p38alpha inhibitors 2h, 2m, and 13h.
      Inhibitor 2m was found to be highly selective for p38alpha/beta over a panel of
      402 other kinases in Ambit screening, and was highly efficacious in vivo in the
      inhibition of TNFalpha production in LPS-stimulated Lewis rats with an ED(50) of
      ca. 0.08mg/kg.

PMID- 20138762
TI  - Acidic elements in histamine H(3) receptor antagonists.
AB  - Antagonists of the human histamine H(3) receptor (hH(3)R) often contain a second
      basic moiety, which is well known to boost affinity on this histamine receptor
      subtype. Here, we prepared compounds with acidic moieties of different pK(a)
      values to figure out that the hH(3)R tolerates these functionalities when added
      to a common pharmacophore blueprint. Depending on the acidic, electronic and
      steric features the designed ligands showed hH(3)R affinities in the nanomolar
      concentration range. Additionally, selected ligands were tested but failed as
      dual acting hH(3)R/hPPAR (human peroxisome proliferator-activated receptor)
      ligands.

PMID- 20138763
TI  - 3-(Arylsulfonyl)-1-(azacyclyl)-1H-indoles are 5-HT(6) receptor modulators.
AB  - Novel 3-(arylsulfonyl)-1-(azacyclyl)-1H-indoles 6 were synthesized as potential 5
      HT(6) receptor ligands, based on constraining a basic side chain as either a
      piperidine or a pyrrolidine. Many of these compounds had good 5-HT(6) binding
      affinity with K(i) values <10nM. Depending on substitution, both agonists (e.g.,
      6o: EC(50)=60nM, E(max)=70%) and antagonists (6y: IC(50)=17 nM, I(max)=86%) were
      identified in a 5-HT(6) adenylyl cyclase assay.

PMID- 20138764
TI  - Metabolic activation of N-thiazol-2-yl benzamide as glucokinase activators:
      Impacts of glutathione trapping on covalent binding.
AB  - Glucokinase activators (GKAs) are currently under investigation as potential
      antidiabetic agents by many pharmaceutical companies. Most of GKAs reported
      previously possess N-aminothiazol-2-yl amide moiety in their structures because
      the aminothiazole moiety interacts with glucokinase (GK) and shows strong GK
      activation. During the development of N-aminothiazol-2-yl amide derivatives, we
      identified a bioactivation and metabolic liability of 2-aminothizole substructure
      of GKA 3 by assessing covalent binding, metabolites in liver microsomes and
      glutathione (GSH) trap assay.

PMID- 20138765
TI  - Light curtain for detecting footfall instants during treadmill walking--an
      exploratory study.
AB  - Footswitches, instrumented insoles, and forceplates are commonly used for
      detecting footfall instants during treadmill walking. This study aimed to explore
      the feasibility of using an optoelectronic light curtain for detecting initial
      foot contact (FC) and toe-off (TO) instants during treadmill walking. A
      commercial light curtain comprised of an array of parallel infrared light beams
      was installed 5 mm above the treadmill belt. Ten subjects walked on the treadmill
      at 0.5, 1.0 and 1.4 m/s and their gait was captured using seven optoelectronic
      cameras. Footswitches were secured over the heel and big toe of the right foot
      and the corresponding areas of the shoe. Footfall instants from the light
      curtain, markers, and foot footswitches were compared with the shoe footswitches
      serving as a criterion. The respective time differences were computed for each
      step and used to evaluate the agreement with the criterion and variability across
      subjects. FC instants from foot footswitches were on average within 10ms of the
      criterion. Both video and light curtain FC instants were detected at least 30 ms
      before the criterion. For TO, both the foot footswitches and video instants
      preceded the criterion. In contrast, the TO from the light curtain occurred >110
      ms after the criterion but the variability was the smallest. The results
      indicated that using a light curtain for detecting footfall instants is feasible.
      The advantages of light curtain are relatively low cost, no subject preparations,
      and real-time signals. Greater accuracy is expected with further optimization of
      the setup.

PMID- 20138766
TI  - An analysis of directional changes in the center of pressure trajectory during
      stance.
AB  - This study proposes a new approach of posturography analysis, which enables the
      evaluation of directional changes in the center of pressure trajectory. The
      concept is similar to that of so-called "stabilogram diffusion analysis". Instead
      of calculating the distance traveled by the center of pressure in a certain time
      interval, this new method calculates the cosine of the instantaneous velocity
      vectors of the center of pressure, which corresponds to the amount of change in
      the sway direction (cosine=1 corresponds to the identical direction; cosine=-1
      corresponds to the opposite direction). This method was applied to the analysis
      of the experimental data in which postural sway was collected under four
      conditions: open eyes, closed eyes, and two auditory biofeedback conditions. In
      the biofeedback conditions, auditory signal was given to the subjects when the
      center of pressure swayed out of a certain area. As results, the differences in
      the postural reaction under these conditions were clearly shown using the new
      method. The results indicated that the subjects reacted to the auditory signals
      by swaying in the opposite direction with biofeedback. It was also found that the
      eyes open condition exhibited a more random-like profile. As this method analyzes
      the directional change in the postural sway, this method can be utilized
      cooperatively together with such a method as stabilogram diffusion analysis,
      which analyzes the magnitude of sway.

PMID- 20138767
TI  - Life with or without AIF.
AB  - Apoptosis-inducing factor (AIF) was initially discovered as a caspase-independent
      death effector. AIF fulfills its lethal function after its release from
      mitochondria and its translocation to the nucleus of the dying cell. The
      contribution of AIF to programmed cell death is dependent upon the cell type and
      apoptotic insult. Recent in vivo data indicate that, in addition to its lethal
      activity, AIF plays a vital mitochondrial role in healthy cells. A segment of AIF
      which is dispensable for its apoptotic function carries an NADH-oxidase domain
      that regulates the respiratory chain complex I and is required for cell survival,
      proliferation and mitochondrial integrity. Mice that express reduced levels of
      AIF constitute a reliable model of complex I deficiency. Here we discuss recent
      reports on the survival-related function(s) of AIF.

PMID- 20138768
TI  - Synthesis and evaluation of 1,4-diphenylbutadiene derivatives as inhibitors of
      plasminogen activator inhibitor-1 (PAI-1) production.
AB  - Butadiene-imide 1 (T-686) derivatives were synthesized and evaluated for their
      inhibitory activity against PAI-1 production and their ADMET (DMPK and
      toxicology) profiles. Among these derivatives, compound 15k (T-2639) showed good
      antithrombotic activity in two rat thrombosis models without affecting bleeding
      time, indicating reduction of haemorrhagic risk. We also describe in this report
      a practical synthesis of 15k suitable for scale-up using Z,E-selective Stobbe
      condensation.

PMID- 20138769
TI  - Design, asymmetric synthesis, and evaluation of pseudosymmetric sulfoximine
      inhibitors against HIV-1 protease.
AB  - The HIV-1 protease is a validated drug target for the design of antiretroviral
      drugs to combat AIDS. We previously established the sulfoximine functionality as
      a valid transition state mimetic (TSM) in the HIV-1 protease inhibitors (PI)
      design and have identified a lead pseudosymmetric compound with nanomolar
      enzymatic inhibitory activity. Here, we report the asymmetric synthesis of this
      compound and its application in the synthesis of sulfoximine-based peptidomimetic
      HIV-1 protease inhibitors. Molecular modeling revealed the potential mode of
      binding of the sulfoximine inhibitor as a TSM. The predicted absolute binding
      free energies suggested similar inhibitory effect as observed in our enzymatic
      inhibitory studies.

PMID- 20138770
TI  - Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as
      anti-inflammatory and neuroprotective agents.
AB  - Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of
      appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted
      benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for
      their anti-inflammatory and neuroprotective properties in vitro. The active
      compounds were further studied in vivo by using the formalin-induced paw edema
      and the turpentine oil-induced granuloma pouch bioassays. We identified four
      novel compounds that showed protective effects in vitro at non-toxic
      concentrations, and were also effective in the animal models of acute and sub
      acute inflammation.

PMID- 20138771
TI  - SAR studies on new bis-aryls 5-HT7 ligands: Synthesis and molecular modeling.
AB  - Structure-activity relationships of a series of bis-arylic compounds,
      investigated as 5-HT(7)R ligands, are reported. The main structural modifications
      involved a central aryl moiety (phenyl, pyridine, diazine, triazine) and the
      nature and position of an amine-containing aliphatic chain. The affinity of the
      synthesized compounds (26 nM-10 microM) was systematically correlated with other
      previously reported series of bis-arylic ligands and rationalized by a ligand
      based pharmacophore approach.

PMID- 20138772
TI  - A validation of computational phantoms from photographic images for patient
      tailored whole body counting.
AB  - This study attempted to validate a new method for patient-tailored efficiency
      calibration. Digital calibration with Monte Carlo simulations was used to
      substitute the lack of precision limitation due to the limited number of
      experimental phantoms in whole body counting calibration for internal dosimetry.
      The validity of this approach was examined by comparing the simulation results to
      the measured values from actual measurements using family BOMAB phantoms. The
      computational voxel phantoms were constructed by a reconstruction technique using
      AP and lateral photographic images of the BOMAB phantoms, instead of using the
      given specifications provided with BOMAB phantoms. Although discrepancies to a
      certain degree between the computational simulation and measured efficiencies do
      exist, the results support the new approach of being an alternative to family
      BOMAB phantoms.

PMID- 20138773
TI  - Compton scatter imaging: A tool for historical exploration.
AB  - This review discusses the principles and technological realisation of a
      technique, termed Compton scatter imaging (CSI), which is based on spatially
      resolved detection of Compton scattered X-rays. The applicational focus of this
      review is to objects of historical interest. Following a historical survey of
      CSI, a description is given of the major characteristics of Compton X-ray
      scatter. In particular back-scattered X-rays allow massive objects to be imaged,
      which would otherwise be too absorbing for the conventional transmission X-ray
      technique. The ComScan (an acronym for Compton scatter scanner) is a commercially
      available backscatter imaging system, which is discussed here in some detail.
      ComScan images from some artefacts of historical interest, namely a fresco, an
      Egyptian mummy and a mediaeval clasp are presented and their use in historical
      analysis is indicated. The utility of scientific and technical advance for not
      only exploring history, but also restoring it, is briefly discussed.

PMID- 20138774
TI  - Induced biosynthesis of resveratrol and the prenylated stilbenoids arachidin-1
      and arachidin-3 in hairy root cultures of peanut: Effects of culture medium and
      growth stage.
AB  - Previously, we have shown that hairy root cultures of peanut provide a
      controlled, sustainable and scalable production system that can be induced to
      produce stilbenoids. However to leverage peanut hairy roots to study the
      biosynthesis of this polyphenolic biosynthetic pathway, growing conditions and
      elicitation kinetics of these tissue cultures must be defined and understood. To
      this end, a new peanut cv. Hull hairy root (line 3) that produces resveratrol and
      its prenylated analogues arachidin-1 and arachidin-3 upon sodium acetate-mediated
      elicitation was established. Two culture media were compared for impact on root
      growth and stilbenoid biosynthesis/secretion. The levels of ammonium, nitrate,
      phosphate and residual sugars were monitored along growth and elicitation period.
      A modified MS (MSV) medium resulted in higher root biomass when compared to B5
      medium. The stilbenoid profile after elicitation varied depending on the age of
      the culture (6, 9, 12, and 15-day old). After elicitation at day 9 (exponential
      growth in MSV medium), over 90% of the total resveratrol, arachidin-1 and
      arachidin-3 accumulated in the medium. Our studies demonstrate the benefits of
      the hairy root culture system to study the biosynthesis of stilbenoids including
      valuable prenylated polyphenolic compounds.

PMID- 20138775
TI  - Increase in catalase-3 activity as a response to use of alternative catabolic
      substrates during sucrose starvation.
AB  - Periods of carbohydrate deprivation are commonly encountered by plant cells.
      Plants respond to this nutrient stress by the mobilization of stored
      carbohydrates and the reallocation of other cellular macromolecules to
      degradative pathways. Previously we identified a number of metabolic genes that
      are upregulated in Arabidopsis thaliana cells during sucrose starvation. One of
      the genes identified encodes acyl-CoA oxidase-4 (ACX4, EC 1.3.3.6), a peroxisomal
      acyl-CoA oxidase that is unique to plants and involved in beta-oxidation of short
      chain fatty acids. Here we demonstrate that ACX4 activity increases during
      sucrose starvation, indicating a shift to a catabolic breakdown of fatty acids as
      a source of available carbon. This suggests a role for degradation of short-chain
      fatty acids in the response to sucrose starvation, leading in turn to the
      production of toxic H2O2. Catalase-3 (CAT3, EC 1.11.1.6) activity also increases
      during starvation as a direct response to the increase in oxidative stress caused
      by the rapid activation of alternative catabolic pathways, including a specific
      increase in ACX4 activity. Any disruption in ACX4 expression or in beta-oxidation
      of fatty acids in general prevents this increase in catalase activity and
      expression. We hypothesize that CAT3 activity increases to remove the H2O2
      produced by alternative catabolic processes induced during the carbohydrate
      shortages caused by extended periods of low-light conditions.

PMID- 20138776
TI  - Transgenic Leucaena leucocephala expressing the Rhizobium gene pydA encoding a
      meta-cleavage dioxygenase shows reduced mimosine content.
AB  - The use of the tree-legume Leucaena leucocephala (leucaena), which contains high
      levels of proteins in its foliage, is limited due to the presence of the toxic
      free amino acid mimosine. The goal of this research was to develop transgenic
      leucaena with reduced mimosine content. Two genes, pydA and pydB, encoding a meta
      cleavage dioxygenase (EC 1.13.11.2) and a pyruvate hydrolase (EC 3.7.1.6),
      respectively, from the mimosine-degrading leucaena symbiont Rhizobium sp. strain
      TAL1145, were used to transform leucaena. These bacterial genes were sequence
      optimized for expression in leucaena and cloned into the plant binary vector
      pCAMBIA3201 for Agrobacterium tumefaciens-mediated transformation. Using immature
      zygotic embryos as the start explant material, six pydA and three pydB transgenic
      lines were developed. The presence and expression of the bacterial genes in the
      transgenic lines were verified by PCR, reverse transcriptase PCR, and Southern
      analyses. HPLC analyses of the transgenic plants determined that the mimosine
      contents of the pydA-expressing lines were reduced up to 22.5% in comparison to
      the wild-type. No significant reduction in mimosine content was observed in the
      pydB-expressing lines. This is the first example of using a gene from a bacterial
      symbiont to reduce the toxicity of a tree-legume.

PMID- 20138777
TI  - Clinical impact of computerised tomographic angiography performed for
      preoperative evaluation before coronary artery bypass grafting.
AB  - OBJECTIVE: In our institution, computerised tomographic (CT) angiography has been
      performed as a near-routine test before coronary artery bypass grafting (CABG) to
      evaluate the aorta and its branches. We aimed to determine its impact on
      operative procedure and perioperative management. METHODS: From January 2006
      through December 2008, neck-to-leg systemic arteries were evaluated by 64-slice
      multidetector CT scan in 284 patients before CABG. For them, medical records and
      cardiac surgery database were retrospectively reviewed to investigate the
      incidence of pathologic lesions of the aorta and its major branches, other
      incidental lesions and procedure- or management-related decision affected by CT
      angiography. RESULTS: In 36 patients (12.7%), cannulation and clamping of the
      ascending aorta were thought too dangerous because of severe atherosclerotic
      change. The use of cardiopulmonary bypass was inevitable in 10 of them, and
      postoperative mortality rate was significantly higher (3/10, 30%) than in the
      remaining patients (2/274, 0.7%). Conduit selection or grafting strategy was
      changed due to severe left subclavian artery stenosis or leg vein varicosity in
      18 patients (6.3%). For the following problems, surgical interventions were
      performed in 34 patients (12.0%) concomitantly or during the same admission with
      CABG; > or = 90% stenosis in carotid (5.6%), iliofemoral (11.6%) or renal (4.6%)
      arteries, aortic aneurysm (14.4%, six of them met surgical indication) and
      incidental malignant neoplasm (2.8%). Counting all of the above, preoperative CT
      angiography affected risk assessment, CABG procedure itself, perioperative
      management or follow-up plan in 142 patients (50%). CONCLUSIONS: Because
      preoperative CT angiography considerably affected management in one half of
      patients, we recommend its use as a routine test before CABG, unless
      contraindicated.

PMID- 20138778
TI  - Does physiotherapy reduce the incidence of postoperative pulmonary complications
      following pulmonary resection via open thoracotomy? A preliminary randomised
      single-blind clinical trial.
AB  - OBJECTIVE: This study investigates whether targeted postoperative respiratory
      physiotherapy decreased the incidence of postoperative pulmonary complications
      and length of stay for patients undergoing elective pulmonary resection via open
      thoracotomy. METHODS: Seventy-six patients participated in a prospective, single
      blind, parallel-group, randomised trial with concealed allocation, assessor
      blinding and intention-to-treat analysis. Treatment group participants received
      daily respiratory physiotherapy interventions until discharge. Control group
      participants received standard medical/nursing care involving a clinical pathway.
      The presence of postoperative pulmonary complications was assessed on a daily
      basis during hospitalisation using a standardised diagnostic tool. Length of stay
      was recorded. RESULTS: Postoperative pulmonary complications developed in two
      participants (4.8%) in the treatment group and in one participant (2.9%) in the
      control group; the difference (treatment minus control) was 1.8% (95% confidence
      interval (CI) -10.6% to 13.1%) (p=1.00). No significant difference was found
      between groups for length of stay (treatment group, median 6.0 days; control
      group 6.0 days) (p=0.87). A preoperative forced expiratory volume in 1s of 1.5l
      or less (p=0.005) and a history of chronic obstructive pulmonary disease
      (p=0.008) were associated with a greater number of criteria for a postoperative
      pulmonary complication being met. CONCLUSIONS: In this patient population, given
      the low incidence of postoperative pulmonary complications, targeted respiratory
      physiotherapy may not be required in addition to standard care involving a
      clinical pathway following pulmonary resection via open thoracotomy. These
      results should be extrapolated with caution to those patients undergoing
      pulmonary resection with poor preoperative lung function.

PMID- 20138779
TI  - Perioperative thrombocytopenia in cardiac surgical patients - incidence of
      heparin-induced thrombocytopenia, morbidities and mortality.
AB  - OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is a life-threatening
      complication of heparin therapy. At our institution, postoperative cardiac
      surgical patients are screened for HIT antibodies, when platelet counts persist
      to be less than 50% of the baseline level or less than 50000 nl(-1). In the
      present study, we compared the outcomes in HIT-antibody-positive and HIT-antibody
      negative patients. METHODS: Patients who underwent a cardiac surgical procedure
      between 1999 and 2007 and in whom a clinical suspicion of HIT prompted a test for
      heparin-dependent platelet-activating antibodies, that is, the heparin-induced
      platelet activation (HIPA) test, were retrieved from the database. Patients were
      divided in group 1 (antibodies present) and group 2 (no antibodies present).
      RESULTS: In 153 of more than 10000 patients (1.5%), a HIPA test was performed, Of
      those, 21 patients tested positive (group 1) and 132 tested negative (group 2).
      Central venous and pulmonary thrombo-embolism was more frequent in group 1 (10%
      vs 2%, p=0.04). Intestinal, microvascular thrombo-embolism was more frequent in
      group 2 (15% as opposed to 0%, p=0.03). By multivariate analysis, only patient
      age (p=0.04, confidence interval (CI): 1.04 (1.00-1.08)), female sex (p=0.03 CI
      3.45 (1.51-7.86)) and perioperative sepsis (p<0.001 CI 6.88 (2.96-16.02)) were
      associated with mortality. CONCLUSION: Patients in whom a low platelet count
      prompted testing for HIT antibodies, had a high mortality (59%), independent of
      whether heparin-dependent antibodies were present, indicating that a persistently
      lowered platelet count is a bad prognostic sign after cardiac surgery.
      Interestingly, the HIPA-positive patients had more central venous and pulmonary
      embolisms. Patient age, female sex and perioperative sepsis were risk factors for
      perioperative mortality.

PMID- 20138780
TI  - Modification of the Ross aortic valve replacement to prevent late autograft
      dilatation.
AB  - OBJECTIVE: Aortic root dilatation with and without aortic regurgitation is seen
      in up to 20% of patients undergoing a Ross aortic root replacement at late follow
      up. We present our early experience with reduction annuloplasty combined with
      prosthetic Dacron graft replacement of the aorta above the autograft to prevent
      late dilation after a Ross aortic root replacement. METHODS: Since 2001, 31 of 97
      adult and paediatric patients (mean age 28.8+/-14.4 years; range 8-53 years) with
      bicuspid aortic valve and dilatation of the ascending aorta underwent a modified
      Ross procedure with reduction annuloplasty combined with prosthetic Dacron graft
      replacement of the ascending aorta. The diameter of the ascending aorta was
      measured before and early after surgery and then between 3 months and 8 years'
      follow-up (mean, 2.5+/-2.2 years). RESULTS: There were no early or late deaths.
      Reduction annuloplasty combined with ascending aortic graft replacement decreased
      the diameters of the ascending aorta from 42+/-7.0mm preoperatively to 25+/-2.9
      mm early after surgery (p<0.001). During follow-up, there was no significant
      increase of the aortic diameter compared with that during the postoperative
      period (27+/-4.3mm; p=0.07). The root diameter increased in only 3 of 31 patients
      (10%). No patient underwent re-operation. At last follow-up, mild (n=18) or
      trivial (n=13) aortic regurgitation was observed. CONCLUSION: Ross aortic root
      replacement combined with reduction annuloplasty and Dacron graft replacement of
      the ascending aorta demonstrated excellent early- to mid-term results in patients
      with bicuspid aortic valve and dilatation of the ascending aorta. Continued use
      and long-term follow-up imaging is necessary to further demonstrate the value of
      this technical modification.

PMID- 20138781
TI  - Sun, vitamin D, and cardiovascular disease.
AB  - Globally, cardiovascular disease (CVD) is the number one cause of death, being
      responsible for approximately 30% of deaths worldwide. Urbanization and a
      westernized lifestyle are thought to play a major role in the development of CVD.
      There is accumulating evidence that vitamin D is a nonclassical risk factor for
      CVD. The active vitamin D metabolite, 1,25-dihydroxyvitamin D, which is
      synthesized from its precursor 25-hydroxyvitamin D (25[OH]D), down-regulates
      several negative and up-regulates various protective pathways in the heart and
      vasculature. First randomized trials demonstrate that vitamin D supplementation
      leads to vasodilatation and suppresses cardiovascular risk markers such as
      triglycerides and the inflammation marker tumor necrosis factor-alpha. Solar UV-B
      radiation is the major source of vitamin D for humans. Consequently, the vitamin
      D status is largely influenced by season, geographic latitude, daily outdoor
      activities, and the percentage of body surface exposed to solar UV-B. A
      significant proportion of individuals in Europe and North America have vitamin D
      concentrations in the deficiency range (25[OH]D<25 nmol/l). Available data
      indicate that low solar UV-B exposure and/or low 25(OH)D concentrations are
      associated with an increased risk of CVD. Large nonrandomized studies indicate
      that CVD mortality is more than twice as high in older individuals with deficient
      25(OH)D concentrations compared with those individuals who have adequate 25(OH)D
      concentrations (>75 nmol/l). Together, experimental and epidemiological evidence
      does support a plausible role for improving vitamin D status in CVD prevention in
      the population at large. Nevertheless, future randomised clinical trials are
      needed to evaluate whether vitamin D is effective with respect to primary,
      secondary, and/or tertiary prevention of CVD.

PMID- 20138783
TI  - Amino acid influence on copper binding to peptides: cysteine versus arginine.
AB  - Matrix assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass
      spectrometry (MS) and theoretical calculations [density functional theory (DFT)]
      were utilized to investigate the influence of cysteine side chain on Cu(+)
      binding to peptides and how Cu(+) ions competitively interact with cysteine (
      SH/SO(3)H) versus arginine. Results from theoretical and experimental
      (fragmentation reactions) studies on [M + Cu](+) and [M + 2Cu - H](+) ions
      suggest that cysteine side chains (-SH) and cysteic acid (-SO(3)H) are important
      Cu(+) ligands. For example, we show that Cu(+) ions are competitively coordinated
      to the -SH or SO(3)H groups; however, we also present evidence that the proton of
      the SH/SO(3)H group is mobile and can be transferred to the arginine guanidine
      group. For [M + 2Cu - H](+) ions, deprotonation of the -SH/SO(3)H group is
      energetically more favorable than that of the carboxyl group, and the resulting
      thiolate/sulfonate group plays an important role in the coordination structure of
      [M + 2Cu - H](+) ions, as well as the fragmentation patterns.

PMID- 20138782
TI  - Bioactive products generated by group V sPLA(2) hydrolysis of LDL activate
      macrophages to secrete pro-inflammatory cytokines.
AB  - OBJECTIVE: Previous studies have established that hydrolysis of LDL by Group V
      secretory phospholipase A(2) (GV sPLA(2)) generates a modified particle capable
      of inducing macrophage foam cell formation. The aim of the present study was to
      determine whether GV sPLA(2)-hydrolyzed LDL (GV-LDL) produces pro-atherogenic
      effects in macrophages independent of cholesterol accumulation. METHODS AND
      RESULTS: J-774 cells incubated with GV-LDL produced more TNF-alpha and IL-6
      compared to cells incubated with control-LDL. Indirect immunofluorescence showed
      that GV-LDL but not control-LDL induced nuclear translocation of NFkappaB.
      Inhibitors of NFkappaB activation, effectively blocked cytokine production
      induced by GV-LDL. Control-LDL and GV-LDL were separated from albumin present in
      reaction mixtures by ultracentrifugation. The albumin fraction derived from GV
      LDL contained 80% of the FFA generated and was more potent than the re-isolated
      GV-LDL in inducing pro-inflammatory cytokine secretion. Linoleic acid (18:2) and
      oleic acid (18:1) were the most abundant FFAs generated, whereas newly formed
      lyso-PCs contained 14:0 (myristic), 16:1 (palmitic), and 18:2 fatty acyl groups.
      Experiments with synthetic FFA showed that 18:1 induced J-774 cells to secrete
      TNF-alpha and IL-6. CONCLUSIONS: These results indicate that in addition to
      promoting atherosclerotic lipid accumulation in macrophages, GV sPLA(2)
      hydrolysis of LDL leads to activation of NFkappaB, a key regulator of
      inflammation.

PMID- 20138784
TI  - Surgery for pseudoaneurysm of the ascending aorta: role of intraoperative 2
      dimensional and real-time 3-dimensional transesophageal echocardiography.

PMID- 20138785
TI  - Unusual short-axis aortic valve view.

PMID- 20138786
TI  - Transfemoral catheter thrombolysis and use of sildenafil in acute massive
      pulmonary embolism.

PMID- 20138787
TI  - Development of a loop-mediated isothermal amplification assay for the detection
      of Mycobacterium bovis.
AB  - Bovine tuberculosis caused by Mycobacterium bovis is an important zoonosis. In
      this study, a simple, rapid method for detecting this organism was developed
      based on loop-mediated isothermal amplification of the mpt83 gene. The technique
      will be of value in the clinical and field-based diagnosis of M. bovis and can
      differentiate it from other bacteria such as Corynebacterium diphtheriae,
      Streptococcus pneumoniae, beta-haemolytic streptococci, Pseudomonas aeruginosa,
      Yersinia pseudotuberculosis, Staphylococcus aureus, and Klebsiella pneumoniae.
      The limit of detection was 10 copies/MUL and the results were corroborated by
      PCR. The method was highly specific and more sensitive than PCR.

PMID- 20138788
TI  - Robotic-assisted treadmill therapy improves walking and standing performance in
      children and adolescents with cerebral palsy.
AB  - OBJECTIVE: Task-specific body-weight-supported treadmill therapy improves walking
      performance in children with central gait impairment. The aim of the study was to
      investigate the effect of robotic-assisted treadmill therapy on standing and
      walking performance in children and adolescents with cerebral palsy and to
      determine parameters influencing outcome. METHODS: 20 Patients (mean age 11.0 +/-
      5.1, 10 males and 10 females) with cerebral palsy underwent 12 sessions of
      robotic-assisted treadmill therapy using the driven gait orthosis Lokomat.
      Outcome measures were the dimensions D (standing) and E (walking) of the Gross
      Motor Function Measure (GMFM). RESULTS: Significant improvements in dimension D
      by 5.9% (+/- 5.2, p=0.001) and dimension E by 5.3% (+/- 5.6, p<0.001) of the GMFM
      were achieved. Improvements in the GMFM D and E were significantly greater in the
      mildly affected cohort (GMFCS I and II) compared to the more severely affected
      cohort (GMFCS III and IV). Improvement of the dimension E but not of D correlated
      positively with the total distance and time walked during the trial (r(s)=0.748,
      p<0.001). CONCLUSIONS: Children and adolescents with bilateral spastic cerebral
      palsy showed improvements in the functional tasks of standing and walking after a
      3-week trial of robotic-assisted treadmill therapy. The severity of motor
      impairment affects the amount of the achieved improvement.

PMID- 20138789
TI  - Reducing data acquisition times in phase-encoded velocity imaging using
      compressed sensing.
AB  - We present a method for accelerating the acquisition of phase-encoded velocity
      images by the use of compressed sensing (CS), a technique that exploits the
      observation that an under-sampled signal can be accurately reconstructed by
      utilising the prior knowledge that it is sparse or compressible. We present
      results of both simulated and experimental measurements of liquid flow through a
      packed bed of spherical glass beads. For this system, the best image
      reconstruction used a spatial finite-differences transform. The reconstruction
      was further improved by utilising prior knowledge of the liquid distribution
      within the image. Using this approach, we demonstrate that for a sampling
      fraction of approximately 30% of the full k-space data set, the velocity can be
      recovered with a relative error of 11%, which is below the visually detectable
      limit. Furthermore, the error in the total flow measured using the CS
      reconstruction is <3% for sampling fractions > or = 30%. Thus, quantitative
      velocity images were obtained in a third of the acquisition time required using
      conventional imaging. The reduction in data acquisition time can also be
      exploited in acquiring images at a higher spatial resolution, which increases the
      accuracy of the measurements by reducing errors arising from partial volume
      effects. To illustrate this, the CS algorithm was used to reconstruct gas-phase
      velocity images at a spatial resolution of 230 microm x 230 microm. Images at
      this spatial resolution are prohibitively time-consuming to acquire using full k
      space sampling techniques.

PMID- 20138790
TI  - Self-refocused slice selection by magic echo DANTE with 270 degrees flipping
      Gaussian RF modulation.
AB  - The method of slice selection proposed for solid-state MRI by combining DANTE
      selective excitation with magic echo (ME) line narrowing requires a rephasing
      period ca. 0.6 times the DANTE excitation period. The added rephasing period
      results in a significant loss of sensitivity due to transverse relaxation. To
      solve the sensitivity problem, we make use of the self-refocusing effect of the
      270 degrees Gaussian-shaped soft pulse by introducing a 270 degrees flipping
      Gaussian modulation to the ME DANTE method. This eliminates the rephasing period.
      The utility of the improved method is demonstrated by experiments performed on
      test samples of adamantane and polycarbonate.

PMID- 20138791
TI  - A quantum chemical study on a set of non-imidazole H3 antihistamine molecules.
AB  - Molecular orbital calculations were carried out on a set of 28 non-imidazole H(3)
      antihistamine compounds using the Hartree-Fock method in order to investigate the
      possible relationships between electronic structural properties and binding
      affinity for H(3) receptors (pK(i)). It was observed that the frontier effective
      for-reaction molecular orbital (FERMO) energies were better correlated with pK(i)
      values than highest occupied molecular orbital (HOMO) and lowest unoccupied
      molecular orbital (LUMO) energy values. Exploratory data analysis through
      hierarchical cluster (HCA) and principal component analysis (PCA) showed a
      separation of the compounds in two sets, one grouping the molecules with high
      pK(i) values, the other gathering low pK(i) value compounds. This separation was
      obtained with the use of the following descriptors: FERMO energies
      (epsilon(FERMO)), charges derived from the electrostatic potential on the
      nitrogen atom (N(1)), electronic density indexes for FERMO on the N(1) atom
      (Sigma((FERMO))c(i)(2)), and electrophilicity (omega'). These electronic
      descriptors were used to construct a quantitative structure-activity relationship
      (QSAR) model through the partial least-squares (PLS) method with three principal
      components. This model generated Q(2)=0.88 and R(2)=0.927 values obtained from a
      training set and external validation of 23 and 5 molecules, respectively. After
      the analysis of the PLS regression equation and the values for the selected
      electronic descriptors, it is suggested that high values of FERMO energies and of
      Sigma ((FERMO))c(i)(2), together with low values of electrophilicity and
      pronounced negative charges on N(1) appear as desirable properties for the
      conception of new molecules which might have high binding affinity.

PMID- 20138792
TI  - Homogentisic acid interference in routine urine creatinine determination.
AB  - We report the artifactual elevation of homogentisic acid (HGA) in urine from
      alkaptonuric patients after replacing the creatinine method (Jaffe reaction) in
      our laboratory with an automated enzymatic method. Samples with elevated HGA by
      GC-MS had lower creatinine values as determined by the enzymatic method than by
      the Jaffe reaction. The low creatinine values were due to interference by HGA in
      the enzymatic method. The enzymatic method is unsuitable for creatinine
      determination in urine of patients with alkaptonuria.

PMID- 20138793
TI  - Increased serum vitamin B12 levels are associated with adult-onset Still's
      disease with reactive macrophage activation syndrome.
AB  - BACKGROUND: Adult-onset Still's disease (AOSD) can be complicated by reactive
      macrophage activation syndrome (rMAS). The objective of this study was to
      evaluate vitamin B(12) values in AOSD with and without rMAS. METHODS: All
      patients' files with AOSD in one center were retrospectively reviewed.
      Hemophagocytosis was defined as phagocytosis of various hematopoietic cells by
      macrophages. Clinical data including fever, rash, sore throat, arthritis,
      lymphadenopathy were recorded. Laboratory tests included complete blood count,
      serum ferritin, transaminases, serum triglyceride and vitamin B(12) level. The
      control group was selected from our AOSD pool who had AOSD without rMAS. RESULTS:
      Seven patients (5 female) had AOSD with rMAS. Median age at the diagnosis of rMAS
      was 32 (range, 27-37) and median follow-up duration after rMAS diagnosis was 18
      months (range, 2-60). All of the patients with rMAS had fever, sore throat, rash,
      arthritis, anemia and hyperferritenemia. Five of seven patients had
      hepatosplenomegaly and lymphadenopathy. Four of seven patients had normal or low
      leucocyte count, three of seven patients had increased triglyceride level. The
      patients with AOSD and rMAS mean+/-standard deviation (S.D.) vitamin B(12) levels
      were significantly higher than without rMAS (1903+/-960 vs 542+/-328pg/ml,
      p=0.001). The specificity (75%) of increased vitamin B(12) level was high and
      sensitivity (100%) was excellent. CONCLUSION: Elevated vitamin B(12) levels seems
      to be a good marker for diagnostic marker in AOSD when complicated with rMAS.

PMID- 20138794
TI  - Pathogenesis of the discal cysts communicating with an adjacent herniated disc.
      Histological and ultrastructual studies of two cases.
AB  - Discal cyst of the lumbar spine is a very rare cause of back pain and sciatica.
      We report two cases of discal cysts communicating with an adjacent herniated
      disc. From CT and MRI findings, they were diagnosed as having a discal cyst in
      the epidural space, which compressed the nerve root. After an adequate surgical
      field was obtained with a microscope and a Casper retractor, the discal cyst
      could be excised and satisfactory decompression of the adjacent nerve root was
      obtained. From histological and electron microscopic study, the presence of
      residual herniated tissues was confirmed in the cyst wall. Macrophages played an
      important role in the absorption of herniated tissue and the formation of the
      discal cyst. Hemorrhage in the cyst wall will make the serous hemorrhagic fluid
      filled cystic structure in the absorbed spaces of the prolapsed disc. In this
      study, we confirmed that the discal cyst could have developed from the absorption
      process of a disc herniation.

PMID- 20138795
TI  - What determines our navigational abilities?
AB  - The ability to find one's way in our complex environments represents one of the
      most fundamental cognitive functions. Although involving basic perceptual and
      memory related processes, spatial navigation is particularly complex because it
      is a multisensory process in which information needs to be integrated and
      manipulated over time and space. Not surprisingly, humans differ widely in this
      ability, and recent animal and human work has begun to unveil the underlying
      mechanisms. Here, we consider three interdependent domains that have been related
      to navigational abilities: cognitive and perceptual factors, neural information
      processing and variability in brain microstructure. Together, the findings
      converge into an emerging model of how different factors interact to produce
      individual patterns of navigational performance.

PMID- 20138796
TI  - Kaposi's sarcoma of the head and neck: a review.
AB  - Important advances in Kaposi's sarcoma (KS) knowledge have been achieved, but KS
      is still a dilemma. It is an angioproliferative disorder classified as an
      intermediate neoplasm due to the absence of conventional clinical features of
      malignancy, but at the moment, it remains unclear if KS could be considered a
      reactive proliferation of endothelial cells and spindle cells, a true malignancy
      or both. In this review, the authors address the main epidemiological, clinical,
      and biological features, of the five types of KS, with emphasis on KS affecting
      the head and neck region. Also, a revision is done in relation with transmission,
      the role of saliva, and the pathogenic events associated with human herpesvirus
      type-8 (HHV-8). Treatment options are revised, highlighting the need for future
      approaches focused on targeting signaling pathways.

PMID- 20138797
TI  - Impact of second primary esophageal or lung cancer on survival of patients with
      head and neck cancer.
AB  - Second cancers following head and neck cancer (HNC) most often involve the
      esophagus and lung, yet the actual magnitude of impact of second primary
      esophageal or lung cancer on survival of HNC patients has not been well
      established, particularly by a large-scale epidemiological study. To provide a
      quantitative estimate of the survival impact, we conducted a population-based
      study including 63,720 cases of HNC subsets, of which 3658 developed at least one
      second primary malignancy, 253 had a second esophageal cancer and 388 had a
      second lung cancer. A Cox proportional hazards model which included age at
      initial cancer diagnosis and gender were employed to compare the survival rates
      between patients with different types of second cancers. Our results showed that
      the second esophageal or lung cancer contributed to a poorer outcome than the
      other types of second cancer, regardless of the index tumor site (all Ps < or =
      0.019). The overall median survival was 0.76+/-0.04 and 0.72+/-0.08 years for
      second esophageal and lung cancers, respectively. Compared to those without
      second cancers, the patients with second esophageal or lung cancer were
      associated with a significant reduction in survival, with an estimated 31-105%
      excess risk of death according to the site of the primary index tumor. In
      conclusion, the second esophageal and lung cancers have a significantly negative
      impact on the survival of HNC patients, thereby calling for a more effective
      program for surveillance and chemoprevention for these two sites.

PMID- 20138798
TI  - Characterization of different tissue changes in normal, betel chewers,
      potentially malignant lesions, conditions and oral squamous cell carcinoma using
      reflectance confocal microscopy: correlation with routine histopathology.
AB  - The goal of this study was to characterize the features of normal mucosa, mucosa
      in betel chewers and smokers, potentially malignant lesions and squamous cell
      carcinoma of oral mucosa using reflectance confocal microscopy. Oral cavity
      biopsies were acquired from 25 patients from College of Dental Surgery, Saveetha
      University who underwent screening for suspected lesions of Oral precancer and
      Oral cancer along with normal patients who underwent impaction. Biopsies were
      acquired from the clinically suspicious area and immediately placed in Dulbecco
      modified eagles growth medium (DMEM). Reflectance confocal images were obtained
      at multiple image plane depths from biopsies within 6h of excision. After
      imaging, biopsies were fixed in 10% formalin and submitted for routine
      histopathological examination by an experienced oral and maxillofacial
      pathologist. Reflectance confocal images were compared with histological images
      from the same sample to determine the tissue features which contribute to early
      cellular changes, image contrast and early diagnosis. The confocal images were
      obtained to a depth of up to 150 microns on intact biopsy specimens and
      subsequent 3-dimensional images, keratin thickness measurements, cell
      measurements, cell density analysis and graphical representations were performed
      using Leica image analysis software. In normal mucosa keratin deposition were
      seen as alternating dark and bright stacks and in different cell layers the
      nuclei were seen as disks of varying intensities. In pre-cancerous lesions the
      keratin thickness and cell nuclear density were found to be increased when
      compared to normal controls. In OSMF cases confocal images of fibrosis show
      scattering from individual fibres as hyperdense areas. Oral squamous cell
      carcinoma cases demonstrated extensive variations in cell size, nuclear size and
      nuclear morphology. At cellular level, dysplastic features like increased nuclear
      density, increased nuclear cytoplasmic ratio, nuclear and cellular pleomorphism
      with loss of cohesiveness were identified in all five cases. Our results support
      the potential of reflectance confocal microscopy to play a significant role in
      clinical evaluations of oral lesions, early diagnosis of potentially malignant
      and malignant oral lesions and real time identification of tumour margins.

PMID- 20138799
TI  - Socio-economic status and head and neck cancer incidence in Canada: a case
      control study.
AB  - In an earlier study we identified an increased incidence of head and neck cancer
      (HNC) in individuals with lower socio-economic status (SES) in the United States.
      The objective of this study was to determine if lower SES is associated with a
      similar increase in the incidence of HNC in Canadian patients. We obtained data
      on SES (income, education and immigration status), demographic characteristics,
      frequency of dental visits and smoking behavior for adult patients residing in
      the Eastern Ontario region who were referred to the Ottawa Regional Cancer Centre
      with HNC. We compared the SES and frequency of dental visits of these HNC
      patients with the SES and frequency of dental visits of a control sample in the
      same region from the 2004-2005 Statistics Canada Canadian Community Health Survey
      (CCHS 3.1). We then performed a logistic regression analysis on the combined
      sample of patients and controls using incidence of HNC as the dependent variable.
      This allowed us to eliminate confounding variables such as tobacco intake and to
      isolate the effect of SES, frequency of dental visits, and immigration status on
      HNC incidence. There was a statistically significant decrease in the incidence of
      HNC among adults with a higher median family income (OR=0.5429, CI=[.3352,
      .8795]). Also, adults with less than grade 8 education had significantly higher
      rates of HNC than adults who had completed high school (OR 3.65, CI=[1.88,
      7.08]). As well, immigrants had a significantly lower incidence of HNC than
      Canadian born adults (OR=0.3825, CI=[.2063, .7090]). Lastly, we found that
      individuals who typically visited a dentist less than once per year had a
      significantly higher incidence of HNC than individuals who typically visited a
      dentist at least once per year (OR=1.69, CI=[1.01, 2.83]). Even when controlling
      for tobacco intake, the incidence of HNC in Eastern Ontario was higher in
      patients with lower median family income and less than grade 8 education. It was
      higher in individuals who visited a dentist less than once per year, and lower in
      immigrants to Canada. This was similar to what has been observed in the United
      States. Further study into the reason for this increased incidence of HNC in
      patients with lower SES is warranted.

PMID- 20138800
TI  - miR-24 up-regulation in oral carcinoma: positive association from clinical and in
      vitro analysis.
AB  - MicroRNAs (miRNAs) play important roles in neoplastic process. miR-24 is
      localized on chromosome 9q22 and 19p13, regions frequently altered in oral
      squamous cell carcinoma (OSCC). This study showed that miR-24 was up-regulated in
      OSCC tissues relative to control samples. In addition, the plasma levels of miR
      24 in OSCC patients were significantly higher than in control individuals. miR-24
      expression was also higher in OSCC cell lines relative to normal oral
      keratinocytes. Experiments blocking miR-24 and using exogenous miR-24 expression
      indicated that miR-24 contributes to the growth of OSCC cells and that miR-24 may
      target p57. This study suggests that miR-24 is involved in the regulation of OSCC
      growth and that the miR-24's level in plasma may be validatable as a tumor marker
      for OSCC patients.

PMID- 20138801
TI  - Crystal structure and EPR studies of doped Cu(2+) ion in [Zn(sac)(2)(en)(2)]
      single crystal.
AB  - The tran-bis(ethylenediamine)bis(saccharinato)Zinc(II), [Zn(sac)(2)(en)(2)]
      (ZSED), (en: ethylenediamine and sac: saccharinate) complex has been synthesized
      and its crystal structure has been determined by X-ray diffraction analysis. The
      compound crystallizes in space group P2(1)/c. The Zn(II) ion is hexa-coordinated
      by four nitrogens of two bidentate en ligands composing the basal plane and two
      nitrogen atoms from the monodentate two sac ligands (N-bonded) occuping the axial
      sites, adopting an elongated octahedral sphere. Both en and sac ligands occupy
      the trans positions of the coordination octahedron. The Zn(II) ion in title
      compound sits on a inversion centre and is octahedrally coordinated two bidentate
      en (ethylenediamine) and two sac (saccharinate) (N-bonded) ligands. The magnetic
      environments of Cu(2+) doped [Zn(sac)(2)(en)(2)] complex have been identified by
      electron paramagnetic resonance (EPR) technique. Cu(2+) doped ZSED single
      crystals have been studied at room temperature in three mutually perpendicular
      planes. The calculated results of the Cu(2+) doped ZSED indicate that Cu(2+) ion
      contains two magnetically inequivalent Cu(2+) sites in distinct orientations
      occupying substitutional positions in the host lattice and show very high angular
      dependence.

PMID- 20138802
TI  - An EPR study of Cu(2+) doped [Na(Hmal)(H(2)O)(5)] single crystals.
AB  - The magnetic environments of Cu(2+) doped Na(+) complex have been identified by
      electron paramagnetic resonance (EPR) technique. The angular variation of the EPR
      spectra has shown that two different Cu(2+) complexes are located in different
      chemical environments, and each environment contains one magnetic Cu(2+) site
      occupying substantial positions in the lattice and showing very high angular
      dependence. The principal g, and the hyperfine structure parameter (A) values of
      two sets of Cu(2+) complex groups are determined. The covalency parameter, mixing
      coefficients and Fermi-contact term of the complex are obtained, and the ground
      state wave function of the Cu(2+) ion in the lattice has been constructed.

PMID- 20138803
TI  - Viral load assay sensitivity and low level viremia in HAART treated HIV patients.
AB  - BACKGROUND: The recent introduction of highly sensitive viral load assays
      resulted in a significant increase in number of treated HIV-infected patients
      with a detectable viral load. The significance of a viral load between 20 and 50
      copies/mL remains unclear. OBJECTIVES: To compare the performance of three viral
      load assays, with special attention for specificity and sensitivity at the lowest
      level of quantification. STUDY DESIGN: Samples (n=181) were selected from 62 HIV
      positive individuals that experience viral blips or episodes of low but
      detectable viremia under antiretroviral treatment, and from 216 HIV-negative
      individuals. Each sample was tested in at least two of three assays: the Cobas
      Amplicor HIV-1 Monitor (CAP/CA), the Cobas Ampliprep/Cobas TaqMan HIV-1 version 1
      (CAP/CTM1) and the Cobas Ampliprep/Cobas TaqMan HIV-1 version 2 (CAP/CTM2).
      RESULTS: No false positive results were recorded. Kappa statistics revealed fair
      to moderate agreement between the results of the three assays, but important
      differences in sensitivity were observed, with the highest sensitivity reported
      for CAP/CTM2 followed by CAP/CTM1 and CAP/CA. The differences in sensitivity
      remained after equalization of the detection limit for all assays at 50
      copies/mL. Analysis of samples collected over time showed that patients with
      single blips in CAP/CA present with recurrent blips in CAP/CTM1 and persistent
      detectable viremia in CAP/CTM2. CONCLUSIONS: Viral load results between 20 and 50
      copies/mL in either CAP/CTM1 or CAP/CTM2, indicate true viremia. The availability
      of highly sensitive assays force reconsideration of the terms 'undetectable'
      viral load and 'virological success' of antiretroviral treatment.

PMID- 20138804
TI  - Identification of G8 rotavirus strains determined as G12 by rotavirus genotyping
      PCR: updating the current genotyping methods.
AB  - BACKGROUND: Rotaviruses are classified into G- and P-types, which are determined
      by the reactivity with antibodies to the outer viral proteins, VP7 and VP4,
      respectively, or sequence variation in the genes encoding these proteins. There
      are presently a number of different rotavirus strains co-circulating within the
      UK, with the common human strains G1P[8], G2P[4] and G9P[8] being the most
      prevalent. As part of strain surveillance for the European Rotavirus Network
      (EuroRotaNet) a cluster (n=29) of G8 strains was detected in the UK between
      February and May 2009. OBJECTIVES: G8 strains were initially mistyped as G12
      through multiplex RT-PCR, therefore further investigation was performed to
      ascertain the reasons behind this mistyping. STUDY DESIGN: The genes encoding the
      VP7 of these G8 strains were sequenced and aligned with the existing G8- and G12
      specific oligonucleotide primers. RESULTS: Multiple alignment of sequences
      derived from these strains and the G8- and G12-specific oligonucleotide primers
      revealed a series of point mutations which resulted in mismatches at the 3' end
      of the G8-specific primer binding site that prevented amplification with the G8
      specific primer, whilst a close homology with the G12-specific primer allowed mis
      priming. Both the G8 and G12 primers were redesigned and their ability to
      correctly identify G8 and G12 strains was evaluated and confirmed. CONCLUSION:
      These findings highlight the importance of monitoring the specificity and
      sensitivity of the genotyping methods in order to detect changes in the genotype
      distribution and changes associated with genetic drift of common or uncommon
      genotypes.

PMID- 20138805
TI  - Incidence and characterization of cytomegalovirus resistance mutations among
      pediatric solid organ transplant patients who received valganciclovir
      prophylaxis.
AB  - BACKGROUND: Drug-resistant cytomegalovirus (CMV) infections can cause significant
      morbidity among high-risk transplant recipients. OBJECTIVES: The aims of this
      study were to determine the incidence and clinical consequences of CMV mutations
      conferring ganciclovir resistance in pediatric solid organ transplant (SOT)
      patients who received valganciclovir oral solution or tablets for prophylaxis of
      CMV disease. Recombinant CMV mutants were also generated to assess the role of
      two UL97 mutations of unknown significance. STUDY DESIGN: Genotypic resistance
      mutations and CMV viral load were sought in blood samples from pediatric SOT
      recipients who received valganciclovir prophylaxis for 100 days. Recombinant
      viruses containing novel CMV UL97 mutations were generated using a bacterial
      artificial chromosome containing the CMV genome to assess ganciclovir
      susceptibility. RESULTS: Overall, four known resistance UL97 mutations were
      observed in blood samples from 2 of 46 patients during the study with no
      development of CMV disease. Two UL97 changes (M615V and V466G) of unknown
      significance and one UL97 mutation (C603R) associated with ganciclovir
      resistance, but not yet confirmed by marker transfer, were also detected.
      Recombinant viruses containing these novel mutations were generated to assess
      ganciclovir susceptibility. The M615V recombinant virus was susceptible to
      ganciclovir while the V466G and C603R mutant viruses displayed 3.5-fold and 3.6
      fold decreases in susceptibility, respectively. CONCLUSIONS: The low incidence of
      ganciclovir resistance-associated mutations and the absence of clinical
      consequences associated with drug-resistant viruses observed in this pilot study
      should encourage the design of larger clinical trials aimed at evaluating the
      efficacy of valganciclovir prophylaxis and treatment in the pediatric setting.

PMID- 20138806
TI  - Clinical application of CT coronary angiography: state of the art.
AB  - In recent years, multi-slice computed tomography (MSCT) technology has developed
      rapidly, allowing high-resolution non-invasive imaging of the coronary arteries
      and surrounding structures. Since the introduction of MSCT, acquisition time,
      detector number, spatial and temporal resolution have continuously improved with
      each new scanner generation, resulting in excellent image quality and diagnostic
      accuracy in the detection of coronary artery disease (CAD). At the same time,
      developments in MSCT technology have focused on reduction of the radiation dose.
      In particular, the availability of dose modulation and prospective ECG gating
      have drastically reduced patient radiation dose. Moreover, with the introduction
      of 320-slice MSCT, volumetric scanning of the entire heart has become possible in
      a single heart beat or gantry rotation, thereby eliminating oversampling and
      stair-step artifact. The present article provides an overview of state of the art
      clinical applications of cardiac MSCT, including the diagnosis of CAD, evaluation
      of plaque morphology and composition, prognostification, and the evaluation of
      left ventricular function and aortic and mitral valve anatomy.

PMID- 20138807
TI  - Cardiovascular magnetic resonance imaging of non-ischaemic heart disease:
      established and emerging applications.
AB  - This review aims to summarise state-of-the-art CMR-methodology, established
      applications, future directions and potentials in the assessment of patients with
      NonIschaemic-Heart Disease. CMR offers the unique possibility to differentiate
      myocardial tissue changes. One of the most challenging tasks in cardiology is the
      differentiation of the underlying cause of a wall motion abnormality in case of
      unclear or conflicting results of conventional clinical assessment CMR offers the
      unique chance to fill that gap. Most of the presented data are ready for use in
      clinical routine.

PMID- 20138808
TI  - Radiotherapy, antihormonal therapy, and personalised medicine.

PMID- 20138809
TI  - Comparison of patient-reported breast, arm, and shoulder symptoms and body image
      after radiotherapy for early breast cancer: 5-year follow-up in the randomised
      Standardisation of Breast Radiotherapy (START) trials.
AB  - BACKGROUND: Few trials of adjuvant breast radiotherapy have incorporated patient
      reported breast symptoms and related areas of quality of life. We assessed these
      measures in a quality-of-life study that was part of the randomised START
      (Standardisation of Breast Radiotherapy) trials. METHODS: In START trial A, 2236
      patients were randomly assigned to receive either 39 Gy or 41.6 Gy delivered in
      13 fractions over 5 weeks or a global standard of 50 Gy in 25 fractions. In START
      trial B, 2215 women were randomly assigned to receive either 40 Gy in 15
      fractions over 3 weeks or the same control regimen (50 Gy in 25 fractions) as in
      trial A. 2739 patients were eligible for the quality-of-life study of whom 2208
      (81%) were accrued (1129 patients from trial A and 1079 from trial B).
      Participants completed the EORTC QLQ-C30 and BR23 questionnaires and protocol
      specific radiotherapy items up to 5 years after radiotherapy. We compared results
      across regimens with generalised estimating equations and survival analyses. The
      START trials are registered, ISRCTN59368779. FINDINGS: At 5 years, up to 40%
      women reported moderate or marked changes to the breast after radiotherapy, and
      arm and shoulder pain affected up to a third of patients. Breast symptoms and
      body image concerns reduced over time. Rates of radiotherapy adverse effects were
      lower for the 39 Gy regimen in trial A and the 40 Gy regimen in trial B, compared
      with the 50 Gy control regimen; rates of radiotherapy adverse effects were
      similar between the 41.6 Gy and 50 Gy regimens in trial A. Adverse change in skin
      appearance was significantly lower for patients who received 39 Gy compared with
      those who received 50 Gy (HR 0.63, 95% CI 0.47-0.84) and for those who received
      40 Gy compared with those who received 50 Gy (0.76, 0.60-0.97); no significant
      difference was observed between patients who received 41.6 Gy and those who
      received 50 Gy in trial A (0.83, 0.63-1.08). Patient self-ratings of breast
      symptoms discriminated a 10% difference in randomised dose intensity. Up to a
      third of women reported moderate or marked pain in the arm and shoulder over 5
      years whilst more than 10% experienced moderate or marked arm and hand swelling,
      with no significant difference in arm/shoulder subscale scores between the
      regimens in trial A or trial B; many baseline arm and shoulder symptoms were
      associated with prior surgery. INTERPRETATION: A substantial proportion of women
      report moderate or marked breast, arm, and shoulder symptoms over 5 years of
      follow-up after radiotherapy, but with no detriment to body image. Nonetheless,
      most patients stand to gain from hypofractionated radiotherapy regimens with a
      potential for fewer adverse effects; this strengthens the evidence from the START
      trials for hypofractionated regimens for women requiring radiotherapy for early
      breast cancer. FUNDING: Cancer Research UK, UK Medical Research Council, UK
      Department of Health.

PMID- 20138810
TI  - Concurrent or sequential adjuvant letrozole and radiotherapy after conservative
      surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial.
AB  - BACKGROUND: Letrozole radiosensitises breast cancer cells in vitro. In clinical
      settings, no data exist for the combination of letrozole and radiotherapy. We
      assessed concurrent and sequential radiotherapy and letrozole in the adjuvant
      setting. METHODS: This phase 2 randomised trial was undertaken in two centres in
      France and one in Switzerland between Jan 12, 2005, and Feb 21, 2007. 150
      postmenopausal women with early-stage breast cancer were randomly assigned after
      conserving surgery to either concurrent radiotherapy and letrozole (n=75) or
      sequential radiotherapy and letrozole (n=75). Randomisation was open label with a
      minimisation technique, stratified by investigational centres, chemotherapy (yes
      vs no), radiation boost (yes vs no), and value of radiation-induced lymphocyte
      apoptosis (< or = 16% vs >16%). Whole breast was irradiated to a total dose of 50
      Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal
      mammary node irradiation, the dose was 44-50 Gy. Letrozole was administered
      orally once daily at a dose of 2.5 mg for 5 years (beginning 3 weeks pre
      radiotherapy in the concomitant group, and 3 weeks post-radiotherapy in the
      sequential group). The primary endpoint was the occurrence of acute (during and
      within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced grade
      2 or worse toxic effects of the skin. Analyses were by intention to treat. This
      study is registered with ClinicalTrials.gov, number NCT00208273. FINDINGS: All
      patients were analysed apart from one in the concurrent group who withdrew
      consent before any treatment. During radiotherapy and within the first 12 weeks
      after radiotherapy, 31 patients in the concurrent group and 31 in the sequential
      group had any grade 2 or worse skin-related toxicity. The most common skin
      related adverse event was dermatitis: four patients in the concurrent group and
      six in the sequential group had grade 3 acute skin dermatitis during
      radiotherapy. At a median follow-up of 26 months (range 3-40), two patients in
      each group had grade 2 or worse late effects (both radiation-induced subcutaneous
      fibrosis). INTERPRETATION: Letrozole can be safely delivered shortly after
      surgery and concomitantly with radiotherapy. Long-term follow-up is needed to
      investigate cardiac side-effects and cancer-specific outcomes. FUNDING: Novartis
      Oncology France.

PMID- 20138811
TI  - Radiotherapy-induced skin changes and quality of life.

PMID- 20138812
TI  - Obstetric analgesia and anaesthesia. Preface.

PMID- 20138813
TI  - Analysis of lidocaine interactions with serum proteins using high-performance
      affinity chromatography.
AB  - High-performance affinity chromatography was used to study binding by the drug
      lidocaine to human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP). AGP
      had strong binding to lidocaine, with an association equilibrium constant (K(a))
      of 1.1-1.7 x 10(5) M(-1) at 37 degrees C and pH 7.4. Lidocaine had weak to
      moderate binding to HSA, with a K(a) in the range of 10(3) to 10(4) M(-1).
      Competitive experiments with site selective probes showed that lidocaine was
      interacting with Sudlow site II of HSA and the propranolol site of AGP. These
      results agree with previous observations in the literature and provide a better
      quantitative understanding of how lidocaine binds to these serum proteins and is
      transported in the circulation. This study also demonstrates how HPAC can be used
      to examine the binding of a drug with multiple serum proteins and provide
      detailed information on the interaction sites and equilibrium constants that are
      involved in such processes.

PMID- 20138814
TI  - Quantification of levetiracetam in plasma of neonates by ultra performance liquid
      chromatography-tandem mass spectrometry.
AB  - A sensitive and specific method using ultra performance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS) was developed for the determination of
      levetiracetam (LEV) in plasma of neonates. A plasma aliquot of 50 microl was
      deproteinized by addition of 500 microl methanol which contained 5 microg/ml UCB
      17025 as an internal standard. After centrifugation, 50 microl of supernatant was
      diluted with 1000 microl of 0.1% formic acid-10 mM ammonium formate in water (pH
      3.5) (mobile phase solution A) and 2 microl was injected onto the UPLC-system.
      Compounds were separated on a Acquity UPLC BEH C(18) 2.1 mm x 100 mm column using
      gradient elution with mobile phase solution A and 0.1% formic acid in methanol
      (mobile phase solution B) with a flow rate of 0.4 ml/min and a total runtime of
      4.0 min. LEV and the internal standard were detected using positive ion
      electrospray ionization followed by tandem mass spectrometry (ESI-MS/MS). The
      assay allowed quantification of LEV plasma concentrations in the range from 0.5
      microg/ml to 150 microg/ml. Inter-assay inaccuracy was within +/-2.7% and inter
      assay precision was less than 4.5%. Matrix effects were minor: the recovery of
      LEV was between 97.7% and 100%. The developed method required minimal sample
      preparation and less plasma sample volume compared to earlier published LC-MS/MS
      methods. The method was successfully applied in a clinical pharmacokinetic study
      in which neonates received intravenous administrations of LEV for the treatment
      of neonatal seizures.

PMID- 20138815
TI  - Polycystic liver diseases.
AB  - Polycystic liver diseases (PCLDs) are genetic disorders with heterogeneous
      etiologies and a range of phenotypic presentations. PCLD exhibits both autosomal
      or recessive dominant pattern of inheritance and is characterized by the
      progressive development of multiple cysts, isolated or associated with polycystic
      kidney disease, that appear more extensive in women. Cholangiocytes have primary
      cilia, functionally important organelles (act as mechanosensors) that are
      involved in both normal developmental and pathological processes. The absence of
      polycystin-1, 2, and fibrocystin/polyductin, normally localized to primary cilia,
      represent a potential mechanism leading to cyst formation, associated with
      increased cell proliferation and apoptosis, enhanced fluid secretion, abnormal
      cell-matrix interactions, and alterations in cell polarity. Proliferative and
      secretive activities of cystic epithelium can be regulated by estrogens either
      directly or by synergizing growth factors including nerve growth factor, IGF1,
      FSH and VEGF. The abnormalities of primary cilia and the sensitivity to
      proliferative effects of estrogens and different growth factors in PCLD cystic
      epithelium provide the morpho-functional basis for future treatment targets,
      based on the possible modulation of the formation and progression of hepatic
      cysts.

PMID- 20138816
TI  - [Validation of the transcutaneous carbon dioxide tension measurements in critical
      paediatric patients].
AB  - OBJECTIVE: To estimate the accuracy of the transcutaneous carbon dioxide tension
      measurement (PtCO(2)) compared to the measurement of the arterial carbon dioxide
      tension (PaCO(2)). MATERIAL AND METHODS: An analytical, longitudinal, prospective
      and observational study, of a dynamic cohort taken from the in-patients of a
      Paediatric Intensive Care Unit (PICU). The PtCO(2) was measured with the SenTec
      AG analyzer, and the sensor was applied with the specific Multi-Site Attachment
      Ring. PtCO(2) and PaCO(2) were recorded at the same time. The statistical
      significance of the association between paired measurements was evaluated with
      the Snedecor's F test, the Pearson's r(2) correlation coefficient and the
      Interclass Correlation Coefficient (ICC). The degree of agreement was evaluated
      with the Bland & Altman method. The consistency of the results was evaluated with
      the ANalysis Of the VAriance (ANOVA). RESULTS: One hundred and six paired
      measurements, PtCO(2) and PaCO(2), from twelve patients, were compared. The means
      of the PaCO(2) and PtCO(2) were 51.0+/-13mmHg and 50.1+/-14mmHg, respectively;
      r(2)=0.87 (p<0.001), ICC=0.96, (95% CI: 0.94-0.97). The Bland-Altman analysis
      showed a mean difference of-0.9mmHg (95% CI:-2.0 to 0.2mmHg). The correlation was
      better in cases with no respiratory disease, with low respiratory assistance,
      with PaCO(2)>50mmHg and with the sensor applied on the forehead. The results were
      consistent. No side effects derived from the use of the ring were observed.
      CONCLUSION: The correlation between PtCO(2) and PaCO(2) is excellent and stable.
      The ring sensor was safe and easy to use.

PMID- 20138817
TI  - Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury.
AB  - Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was
      previously shown to mediate cardioprotection during myocardial
      ischemia/reperfusion injury through large complexes of 50-100 nm. Here we show
      that these MSCs secreted 50- to 100-nm particles. These particles could be
      visualized by electron microscopy and were shown to be phospholipid vesicles
      consisting of cholesterol, sphingomyelin, and phosphatidylcholine. They contained
      coimmunoprecipitating exosome-associated proteins, e.g., CD81, CD9, and Alix.
      These particles were purified as a homogeneous population of particles with a
      hydrodynamic radius of 55-65 nm by size-exclusion fractionation on a HPLC.
      Together these observations indicated that these particles are exosomes. These
      purified exosomes reduced infarct size in a mouse model of myocardial
      ischemia/reperfusion injury. Therefore, MSC mediated its cardioprotective
      paracrine effect by secreting exosomes. This novel role of exosomes highlights a
      new perspective into intercellular mediation of tissue injury and repair, and
      engenders novel approaches to the development of biologics for tissue repair.

PMID- 20138818
TI  - Research projects on jaw function and occlusion published in 2008 by members of
      the Japan Prosthodontic Society: a review.
AB  - This article reviews the findings of 5 original papers in the areas of jaw
      function published in the Journal of the Japan Prosthodontic Society (J Japan
      Prosthodontic Soc; Nippon Hotetsu Shika Gakkai Zasshi in Medline/PubMed; issued
      in Volume 52, 2008). A variety of subjects in relation to body movement
      associated with mandibular movement, parameters for mandibular movement analysis,
      system evaluation for a new jaw tracking device and obstructive sleep apnea were
      examined in the listed articles.

PMID- 20138819
TI  - Malaria vectors in the Republic of Benin: distribution of species and molecular
      forms of the Anopheles gambiae complex.
AB  - Members of the Anopheles gambiae complex are among the best malaria vectors in
      the world, but their vectorial capacities vary between species and populations. A
      large-scale sampling of An. gambiae sensu lato was carried out in 2006 and 2007
      in various bioclimatic areas of Benin (West Africa). The objective of this study
      was to collate data on the relative frequencies of species and forms within the
      An. gambiae complex and to produce a map of their spatial distribution. Sampling
      took place at 30 sites and 2122 females were analyzed. Two species were
      identified through molecular methods. The overall collection showed a
      preponderance of An. gambiae s.s., but unexpectedly, An. arabiensis was reported
      in the coastal-Guinean bioclimatic area characterized by a mean annual rainfall
      of >1500 mm where only An. gambiae s.s. was reported previously. Our study of
      Benin indicates that An. arabiensis would be adapted not only to the urban areas
      but also to the rural humid regions. Among 1717 An. gambiae s.s., 26.5% were of
      the M form and 73.3% were S form. Few hybrid specimens between the M and S forms
      were observed (0.2%). Only the spatial distribution of the M form appears to be
      mainly a function of bioclimatic area. Factors that influence the distribution of
      these malaria vectors are discussed. This study underlines the need of further
      investigations of biological, ecological, and behavioral traits of these species
      and forms to better appreciate their vectorial capacities. Acquisition of
      entomological field data appears essential to better estimate the stratification
      of malaria risk and help improve malaria vector control interventions.

PMID- 20138820
TI  - Early transcriptional response to chloroquine of the Plasmodium falciparum
      antioxidant defence in sensitive and resistant clones.
AB  - Resistance to chloroquine (CQ) in Plasmodium falciparum has a major impact on
      malaria control worldwide. To gain insight into early parasite stress response,
      mRNA expression profiles were determined for a set of 10 antioxidant defence
      genes in synchronized CQ-sensitive (3D7) and CQ-resistant (Dd2) clones under
      transient IC50 CQ-exposure (Dd2, 200 nM; 3D7, 14 nM). Upon 2-h CQ challenge, the
      mRNA upregulation detected was greater in 3D7 (six genes overexpressed at 1/3 of
      the intraerythrocytic cycle) than in Dd2 clone (three genes responding),
      providing evidence of an early transcriptional response to CQ-induced oxidative
      stress which might underlie some of the parasite's metabolic adaptation to the
      drug.

PMID- 20138821
TI  - Characterization of human VDAC isoforms: a peculiar function for VDAC3?
AB  - VDACs are a family of pore-forming proteins mainly located in the mitochondrial
      outer membrane. In mammals three isoforms exist. In this work we review the
      information available about them with the addition of new results. We have
      compared the human VDACs transformed in a yeast strain lacking the endogenous
      porin. VDAC1 and 2 are able to complement the lack of porin in mitochondrial
      respiration and modulation of ROS. VDAC3 has a limited ability to support the
      mitochondrial respiration and has no influence in the control of ROS production.
      The over-expression of VDAC isoforms in wild type yeast strain led to a dramatic
      sensitivity to oxidative stress, especially for VDAC3, and a shorter lifespan in
      respiratory conditions. Real-time PCR comparison of the isoforms indicated that
      in HeLa cells VDAC1 is 10 times more abundant than VDAC2 and 100 times than
      VDAC3. The over-expression of any single isoform caused a 10 times increase of
      the transcripts of VDAC2 and VDAC3, while VDAC1 is not changed by the over
      expression of the other isoforms. Models of VDAC2 and VDAC3 isoform structure
      showed that they could be made of a 19-strand beta-barrel and an N-terminal
      sequence with variable features. In this work we show for the first time a
      functional characterization of VDAC3 in a cellular context.

PMID- 20138822
TI  - Interaction between CFTR and prestin (SLC26A5).
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated
      chloride channel that is present in a variety of epithelial cell types, and
      usually expressed in the luminal membrane. In contrast, prestin (SLC26A5) is a
      voltage-dependent motor protein, which is present in the basolateral membrane of
      cochlear outer hair cells (OHCs), and plays an important role in the frequency
      selectivity and sensitivity of mammalian hearing. By using in situ hybridization
      and immunofluorescence, we found that both mRNA and protein of CFTR are present
      in OHCs, and that CFTR localizes in both the apical and the lateral membranes.
      CFTR was not detected in the lateral membrane of inner hair cells (IHCs) or in
      that of OHCs derived from prestin-knockout mice, i.e., in instances where prestin
      is not expressed. These results suggest that prestin may interact physically with
      CFTR in the lateral membrane of OHCs. Immunoprecipitation experiments confirmed a
      prestin-CFTR interaction. Because chloride is important for prestin function and
      for the efferent-mediated inhibition of cochlear output, the prestin-directed
      localization of CFTR to the lateral membrane of OHCs has a potential
      physiological significance. Aside from its role as a chloride channel, CFTR is
      known as a regulator of multiple protein functions, including those of the solute
      carrier family 26 (SLC26). Because prestin is in the SLC26 family, several
      members of which interact with CFTR, we explored the potential modulatory
      relationship associated with a direct, physical interaction between prestin and
      CFTR. Electrophysiological experiments demonstrated that cAMP-activated CFTR is
      capable of enhancing voltage-dependent charge displacement, a signature of OHC
      motility, whereas prestin does not affect the chloride conductance of CFTR.

PMID- 20138823
TI  - Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c.
AB  - The release of cytochrome c from the mitochondrial intermembrane space is a
      decisive event in programmed cell death. Once in the cytoplasm, cytochrome c is
      involved in the formation of the macromolecular complex termed apoptosome, which
      activates procaspase-9 which in turn activates downstream procaspase-3. There are
      increasing evidence indicating that cyclophilin A is highly expressed in many
      tumors and cell lines where it exerts an anti-apoptotic function. In brain
      tissue, which over-expresses constitutively cyclophilin A, we found mixed dimers
      composed of cyclophilin A and cytochrome c. In a cell-free system we observed
      that pure cyclophilin A inhibited cytochrome c-dependent procaspase-3 activation.
      Moreover, we detected cyclophilin A-cytochrome c complexes within the cytoplasm
      of HCT116 cells following staurosporine-induced apoptosis. Our results strongly
      support that, in tumor cells, cyclophilin A is able to inhibit procaspase-3
      activation by sequestering cytochrome c.

PMID- 20138824
TI  - Crystal structure of a thermostable old yellow enzyme from Thermus scotoductus SA
      01.
AB  - Recent characterization of the chromate reductase (CrS) from the thermophile
      Thermus scotoductus SA-01 revealed this enzyme to be related to the Old Yellow
      Enzyme (OYE) family. Here, we report the structure of a thermostable OYE homolog
      in its holoform at 2.2A as well as its complex with p-hydroxybenzaldehyde (pHBA).
      The enzyme crystallized as octamers with the monomers showing a classical TIM
      barrel fold which upon dimerization yields the biologically active form of the
      protein. A sulfate ion is bound above the si-side of the non-covalently bound FMN
      cofactor in the oxidized solved structure but is displaced upon pHBA binding. The
      active-site architecture is highly conserved as with other members of this enzyme
      family. The pHBA in the CrS complex is positioned by hydrogen bonding to the two
      conserved catalytic-site histidines. The most prominent structural difference
      between CrS and other OYE homologs is the size of the "capping domain".
      Thermostabilization of the enzyme is achieved in part through increased proline
      content within loops and turns as well as increased intersubunit interactions
      through hydrogen bonding and complex salt bridge networks. CrS is able to reduce
      the C=C bonds of alpha,beta-unsaturated carbonyl compounds with a preference
      towards cyclic substrates however no activity was observed towards beta
      substituted substrates. Mutational studies have confirmed the role of Tyr177 as
      the proposed proton donor although reduction could still occur at a reduced rate
      when this residue was mutated to phenylalanine.

PMID- 20138825
TI  - SOX2 modulates alternative splicing in transitional cell carcinoma.
AB  - Aberrant alternative splicing of key cellular regulators may play a pivotal role
      in cancer development. To investigate the potential influence of altered
      alternative splicing on the development of transitional cell carcinoma (TCC),
      splicing activity in the TCC cell lines TSGH8301 and BFTC905 was examined using
      the SV40-immortalized uroepithelial cell line SV-HUC-1 as a reference. Our
      results indicate a significant alteration in splice site selection in the TCC
      cell lines. By gene expression profiling and subsequent validation, we discovered
      that sex-determining region Y-box protein 2 (SOX2) is specifically upregulated in
      BFTC905. Furthermore, ectopic expression of SOX2 modulates alternative splicing
      of the splicing reporter in vivo. More significantly, using an in vitro pull-down
      assay, it was found that SOX2 exhibits RNA-binding capability. Our observations
      suggest that SOX2 modulates alternative splicing by functioning as a splicing
      factor.

PMID- 20138826
TI  - Activation of Na+/H+ exchanger 1 by neurotensin signaling in pancreatic cancer
      cell lines.
AB  - Acidosis commonly observed in solid tumors like pancreatic cancer promotes
      genetic instability and selection of a more malignant phenotype of cancer cells.
      Overexpression or activation of integral membrane proteins mediating H+ efflux
      may contribute to extracellular acidification. Neurotensin (NT) induces
      intracellular alkalinization and stimulates interleukin-8 production in
      pancreatic cancer cells and, as demonstrated here, the stable NT analog Lys(8)
      psi-Lys(9)NT(8-13) enhances the amiloride-sensitive, Na+-dependent transmembrane
      H+ flux by a factor of 2.05+/-0.28 and 2.69+/-0.07 in BxPC-3 and PANC-1
      pancreatic cancer cells, respectively, by phosphorylation of the Na+/H+ exchanger
      1 (NHE1). Human genome-wide gene expression analysis was performed to detect
      effects of Lys(8)-psi-Lys(9)NT(8-13) on BxPC-3 cells. Results indicated
      upregulation of genes involved in regulation of NHE1, hypoxic response and
      glycolysis in response to Lys(8)-psi-Lys(9)NT(8-13) even under normoxic
      conditions. Therefore, our findings suggest that growth factors like NT may be
      implicated in the early progression of pancreatic cancer by localized
      acidification and induction of an aerobic glycolytic phenotype with higher
      metastatic potential in small cell aggregates.

PMID- 20138827
TI  - Similar incretin secretion in obese and non-obese Japanese subjects with type 2
      diabetes.
AB  - Incretin secretion and effect on insulin secretion are not fully understood in
      patients with type 2 diabetes. We investigated incretin and insulin secretion
      after meal intake in obese and non-obese Japanese patients with type 2 diabetes
      compared to non-diabetic subjects. Nine patients with type 2 diabetes and 5 non
      diabetic subjects were recruited for this study. Five diabetic patients were
      obese (BMI > or = 25) and 4 patients were non-obese (BMI < 25). In response to a
      mixed meal test, the levels of immunoreactive insulin during 15-90 min and C
      peptide during 0-180 min in non-obese patients were significantly lower than
      those in obese patients. Total GLP-1 and active GIP levels showed no significant
      difference between obese and non-obese patients throughout the meal tolerance
      test. In addition, there were no significant differences between diabetic
      patients and non-diabetic subjects. In conclusion, incretin secretion does not
      differ between Japanese obese and non-obese patients with type 2 diabetes and non
      diabetic subjects.

PMID- 20138828
TI  - MicroRNA-mediated signaling involved in plant root development.
AB  - MicroRNA (miRNA), recently recognized as a critical post-transcriptional
      modulator of gene expression, is involved in numerous biological processes in
      both animals and plants. Although eudicots and monocots, such as the model plants
      Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), possess distinct root
      systems, several homologous miRNA families are reported to be involved in root
      growth control in both plants. Consistent with recent notion that numerous
      signaling pathways are implicated in root development, these miRNAs are
      implicated in auxin signaling, nutrition metabolism, or stress response and have
      potential role in mediating the signal interactions. However, a recapitulative
      representation of these results is especially desired. This review provides a
      global view of the involvement of miRNAs in root development focusing on the two
      plants, Arabidopsis and rice. Based on current research advances, several
      innovative mechanisms of miRNA transcription, feedback regulatory circuit between
      miRNAs and transcription factors (TFs), and miRNA-mediated signal interactions
      are also discussed.

PMID- 20138829
TI  - Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K
      inhibitor in MCF-7 cells.
AB  - Curcumin has been shown to induce apoptosis in various malignant cancer cell
      lines. One mechanism of curcumin-induced apoptosis is through the PI3K/Akt
      signaling pathway. Akt, also known as protein kinase B (PKB), is a member of the
      family of phosphatidylinositol 3-OH-kinase regulated Ser/Thr kinases. The active
      Akt regulates cell survival and proliferation; and inhibits apoptosis. In this
      study we found that curcumin induces apoptotic cell death in MCF-7 cells, as
      assessed by MTT assay, DNA ladder formation, PARP cleavage, p53 and Bax
      induction. At apoptotic inducing concentration, curcumin induces a dramatic Akt
      phosphorylation, accompanied by an increased phosphorylation of glycogen synthase
      kinase 3beta (GSK3beta), which has been considered to be a pro-growth signaling
      molecule. Combining curcumin with PI3K inhibitor, LY290042, synergizes the
      apoptotic effect of curcumin. The inhibitor LY290042 was capable of attenuating
      curcumin-induced Akt phosphorylation and activation of GSK3beta. All together,
      our data suggest that blocking the PI3K/Akt survival pathway sensitizes the
      curcumin-induced apoptosis in MCF-7 cells.

PMID- 20138830
TI  - Chronic hepatitis C viral infection reduces NK cell frequency and suppresses
      cytokine secretion: Reversion by anti-viral treatment.
AB  - Impaired activity of NK (natural killer) cells has been proposed as a mechanism
      contributing to viral persistence and chronic infection in hepatitis C (HCV)
      infection. We aimed to assess the impact of HCV infection on NK cells regarding
      frequency, subset distribution, and cytotoxic and cytokine secretion functions,
      as well as IFN-alpha and ribavirin therapeutic effects on NK cells. Significant
      reduction of total NK frequency and the CD56(dim)16(+) subset was observed in
      chronic HCV patients. IFN-gamma expression upon stimulation with K562 was
      severely suppressed but cytotoxicity measured by CD107a expression was
      maintained. These adverse effects were reversed after treatment with pegylated
      IFN-alpha and ribavirin; however, these skewed functions were not recovered in
      treatment-resistant patients. Thus, HCV chronic infection severely affects NK
      functions, except for cytotoxicity. Altered NK cell frequency and cytokine
      secretion by HCV infection may contribute to impaired cellular immune response
      and virus persistence.

PMID- 20138831
TI  - Hydrogen-rich saline ameliorates the severity of l-arginine-induced acute
      pancreatitis in rats.
AB  - Molecular hydrogen, which reacts with the hydroxyl radical, has been considered
      as a novel antioxidant. Here, we evaluated the protective effects of hydrogen
      rich saline on the l-arginine (l-Arg)-induced acute pancreatitis (AP). AP was
      induced in Sprague-Dawley rats by giving two intraperitoneal injections of l-Arg,
      each at concentrations of 250mg/100g body weight, with an interval of 1h.
      Hydrogen-rich saline (>0.6mM, 6ml/kg) or saline (6ml/kg) was administered,
      respectively, via tail vein 15min after each l-Arg administration. Severity of AP
      was assessed by analysis of serum amylase activity, pancreatic water content and
      histology. Samples of pancreas were taken for measuring malondialdehyde and
      myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and
      nuclear factor kappa B (NF-kappaB) were detected with immunohistochemistry.
      Hydrogen-rich saline treatment significantly attenuated the severity of l-Arg
      induced AP by ameliorating the increased serum amylase activity, inhibiting
      neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover,
      hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit
      apoptosis and NF-kappaB activation. These results indicate that hydrogen
      treatment has a protective effect against AP, and the effect is possibly due to
      its ability to inhibit oxidative stress, apoptosis, NF-kappaB activation and to
      promote acinar cell proliferation.

PMID- 20138832
TI  - Direct interaction between Utp8p and Utp9p contributes to rRNA processing in
      budding yeast.
AB  - The small subunit (SSU) processome is an evolutionarily conserved
      ribonucleoprotein (RNP) complex that consists of U3 snoRNA and at least 40
      protein components. The SSU processome is required for the generation of 18S rRNA
      in the budding yeast Saccharomyces cerevisiae. In this study we demonstrate that
      two essential components of the SSU processome, Utp8p and Utp9p, must interact
      directly for the SSU processome to function properly. Disruption of the Utp8p
      Utp9p interaction by mutation of the respective interacting domain led to a
      compromised ability of yeast cells to process 35S pre-rRNA into 18S pre-rRNA.
      Loss of the Utp8p-Utp9p interaction also led to a decrease in the amount of Utp8p
      that interacted with U3 small nucleolar RNAs (snoRNAs) but did not affect the
      amount of Utp9p bound to U3 snoRNA, suggesting that Utp8p associates with the SSU
      processome by virtue of its interaction with Utp9p. Together, our data support a
      model where Utp8p and Utp9p must interact directly and functionally in the U3
      containing SSU processome for optimal rRNA biosynthesis to occur in budding
      yeast.

PMID- 20138833
TI  - Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived
      mesenchymal stem cells for cell therapy in regenerative medicine.
AB  - Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation
      into multiple cell lineages. Presently, bone marrow is considered as a prime
      source of MSCs; however, there are some drawbacks and limitations in use of these
      MSCs for cell therapy. In this study, we demonstrate that human gingival tissue
      derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs
      are easy to isolate, homogenous and proliferate faster than bone marrow MSCs
      without any growth factor. Importantly, gingival MSCs display stable morphology
      and do not loose MSC characteristic at higher passages. In addition, gingival
      MSCs maintain normal karyotype and telomerase activity in long-term cultures, and
      are not tumorigenic. Thus, we reveal that human gingiva is a better source of
      MSCs than bone marrow, and large number of functionally competent clinical grade
      MSCs can be generated in short duration for cell therapy in regenerative medicine
      and tissue engineering.

PMID- 20138834
TI  - Highly selective fusion and accumulation of hybrid liposomes into primary
      effusion lymphoma cells along with induction of apoptosis.
AB  - Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpes
      virus-8 infection, and is generally resistant to chemotherapy. Hybrid liposomes,
      composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (21)
      dodecyl ether (C12(EO)21) (HL-21), were rapidly accumulated in the membrane of
      PEL cells. HL-21 also increased membrane fluidity of PEL cells, and induced
      caspase-3 activation along with cell death. These results suggest that HL-21
      should be an effective and attractive regent for PEL treatment.

PMID- 20138835
TI  - Microdeletions within the hydrophobic core region of cellular prion protein alter
      its topology and metabolism.
AB  - The cellular prion protein (PrP(C)) is a GPI-anchored cell-surface protein. A
      small subset of PrP(C) molecules, however, can be integrated into the ER-membrane
      via a transmembrane domain (TM), which also harbors the most highly conserved
      regions of PrP(C), termed the hydrophobic core (HC). A mutation in HC is
      associated with prion disease resulting in an enhanced formation of a
      transmembrane form ((Ctm)PrP), which has thus been postulated to be a neurotoxic
      molecule besides PrP(Sc). To elucidate a possible physiological function of the
      transmembrane domain, we created a set of mutants carrying microdeletions of 2-8
      aminoacids within HC between position 114 and 121. Here, we show that these
      mutations display reduced propensity for transmembrane topology. In addition, the
      mutants exhibited alterations in the formation of the C1 proteolytic fragment,
      which is generated by alpha-cleavage during normal PrP(C) metabolism, indicating
      that HC might function as recognition site for the protease(s) responsible for
      PrP(C) alpha-cleavage. Interestingly, the mutant G113V, corresponding to a
      hereditary form of prion disease in humans, displayed increased (Ctm)PrP topology
      and decreased alpha-cleavage in our in vitro assay. In conclusion, HC represents
      an essential determinant for transmembrane PrP topology, whereas the high
      evolutionary conservation of this region is rather based upon preservation of
      PrP(C) alpha-cleavage, thus highlighting the biological importance of this
      cleavage.

PMID- 20138836
TI  - Cholesterol accumulation in Niemann Pick type C (NPC) model cells causes a shift
      in APP localization to lipid rafts.
AB  - It has been suggested that cholesterol may modulate amyloid-beta (Abeta)
      formation, a causative factor of Alzheimer's disease (AD), by regulating
      distribution of the three key proteins in the pathogenesis of AD (beta-amyloid
      precursor protein (APP), beta-secretase (BACE1) and/or presenilin 1 (PS1)) within
      lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1
      dysfunction, which causes Niemann Pick type C disease (NPC), causes increased
      partitioning of APP into lipid rafts leading to increased CTF/Abeta formation in
      these cholesterol-rich membrane microdomains. To test this we used CHO NPC1(-/-)
      cells (NPC cells) and parental CHOwt cells. By sucrose density gradient
      centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid
      raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore,
      gamma-secretase inhibitor treatment significantly increased fl-APP/CTF
      distribution in raft fractions in NPC vs. wt cells, suggesting that upon
      cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and
      its increased processing towards Abeta occurs in lipid rafts. Our results support
      that cholesterol overload, such as in NPC disease, leads to increased
      partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic
      processing of APP in these cholesterol-rich membranes. This work adds to the
      mechanism of the cholesterol-effect on APP processing and the pathogenesis of
      Alzheimer's disease and supports the role of lipid rafts in these processes.

PMID- 20138837
TI  - Lipid raft cholesterol and genistein inhibit the cell viability of prostate
      cancer cells via the partial contribution of EGFR-Akt/p70S6k pathway and down
      regulation of androgen receptor.
AB  - Soy isoflavones and cholesterol have been reported as dietary factors related to
      the incidence of prostate cancer. In this study, we investigated whether cell
      survival could be suppressed by a combination of the dispersion of lipid raft
      microdomains and treatment with genistein, a well-known potential isoflavone, in
      LNCaP prostate cancer cells. Cell viability was assayed by the property of
      reagent change upon reduction of resazurin to resorufin and apoptosis was
      evaluated by ethidium bromide/acridine orange (EB/AO) staining and PARP and
      caspase-3 expression. Signal transduction was investigated by immunoblot
      analysis. Cell viability decreased significantly more following successive double
      treatment with genistein and the cholesterol-lowering agent 2-hydroxypropyl-beta
      cyclodextrin (HPCD) than in response to either agent alone. Apoptotic cell
      staining and cleavage of PARP and caspase-3 appeared more clearly in double
      treated cells than in those treated with genistein alone. In cell signaling, both
      HPCD and genistein decreased the protein expressions of pAkt as well as the
      androgen receptors stimulated by EGF and DHT, respectively, in concentration
      dependent manners. This pattern was also present in protein levels of pAkt and
      the androgen receptor located in the lipid raft fraction. Furthermore, the
      phosphorylation cascade of Akt, GSK-3beta and p70S6k was markedly inhibited by
      the combination treatment. These data suggest that prostate cancer cells could be
      effectively inhibited by combination treatment of cholesterol-lowering strategies
      and genistein. The mechanism is likely to be partially via both the EGFR-mediated
      Akt or p70S6k pathways and a down-regulation of androgen receptor in the lipid
      raft microdomain.

PMID- 20138838
TI  - O-GlcNAc inhibits interaction between Sp1 and sterol regulatory element binding
      protein 2.
AB  - O-linked N-acetylglucosamine (O-GlcNAc), a monosaccharide N-acetylglucosamine on
      the serine and threonine residues of nucleocytoplasmic proteins, is a novel
      protein modification that is ubiquitous among eukaryotes and implicated in cell
      regulation. Recent evidence indicates that O-GlcNAc regulates protein-protein
      interactions. Here we provide evidence that O-GlcNAc interrupts a known
      interaction between Sp1 and sterol regulatory element binding protein 2 (SREBP2),
      thereby inhibiting expression of the gene encoding acetyl-CoA synthetase 1, which
      is involved in lipid synthesis. This study suggests a novel mechanism in which
      lipid biosynthesis may be regulated by O-GlcNAc.

PMID- 20138839
TI  - A vacuolar carboxypeptidase mutant of Arabidopsis thaliana is degraded by the
      ERAD pathway independently of its N-glycan.
AB  - Misfolded proteins produced in the endoplasmic reticulum (ER) are degraded by a
      mechanism, the ER-associated degradation (ERAD). Here we report establishment of
      the experimental system to analyze the ERAD in plant cells. Carboxypeptidase Y
      (CPY) is a vacuolar enzyme and its mutant CPY* is degraded by the ERAD in yeast.
      Since Arabidopsis thaliana has AtCPY, an ortholog of yeast CPY, we constructed
      and expressed fusion proteins consisting of AtCPY and GFP and of AtCPY*, which
      carries a mutation homologous to yeast CPY*, and GFP in A. thaliana cells. While
      AtCPY-GFP was efficiently transported to the vacuole, AtCPY*-GFP was retained in
      the ER to be degraded in proteasome- and Cdc48-dependent manners. We also found
      that AtCPY*-GFP was degraded by the ERAD in yeast cells, but that its single N
      glycan did not function as a degradation signal in yeast or plant cells.
      Therefore, AtCPY*-GFP can be used as a marker protein to analyze the ERAD
      pathway, likely for nonglycosylated substrates, in plant cells.

PMID- 20138840
TI  - Regulation of hepatic branched-chain alpha-keto acid dehydrogenase kinase in a
      rat model for type 2 diabetes mellitus at different stages of the disease.
AB  - Branched-chain alpha-keto acid dehydrogenase (BCKDH) kinase (BDK) is responsible
      for the regulation of BCKDH complex, which is the rate-limiting enzyme in the
      catabolism of branched-chain amino acids (BCAAs). In the present study, we
      investigated the expression and activity of hepatic BDK in spontaneous type 2
      diabetes using hyperinsulinemic Zucker diabetic fatty rats aged 9weeks and
      hyperglycemic, but not hyperinsulinemic rats aged 18weeks. The abundance of
      hepatic BDK mRNA and total BDK protein did not correlate with changes in serum
      insulin concentrations. On the other hand, the amount of BDK bound to the complex
      and its kinase activity were correlated with alterations in serum insulin levels,
      suggesting that hyperinsulinemia upregulates hepatic BDK. The activity of BDK
      inversely corresponded with the BCKDH complex activity, which was suppressed in
      hyperinsulinemic rats. These results suggest that insulin regulates BCAA
      catabolism in type 2 diabetic rats by modulating the hepatic BDK activity.

PMID- 20138841
TI  - Microarray analysis of tonsils in immunoglobulin A nephropathy patients.
AB  - BACKGROUND: Recently, combination of tonsillectomy and steroid pulse therapy was
      reported to be effective as the treatment of the immunoglobulin A nephropathy
      (IgAN). However, the gene expression difference between the tonsils in patients
      with IgAN and those in control patients is not established. METHODS: We performed
      tonsillectomy combined with steroid pulse as a treatment to IgAN, analyzed the
      gene expression in the tonsils (N=23) using microarray, compared with those with
      patients suffering from chronic tonsillitis (N=22). From some candidate genes
      related with IgAN, we confirmed the apolipoprotein B messenger RNA-editing enzyme
      catalytic polypeptides 2 (APOBEC2) gene expression in the tonsil and we also
      analyzed its expression levels and clinical features. RESULTS: Up-regulated genes
      seem to be categorized into two groups. One group belongs to the muscle related
      genes which might be caused by structural differences. The other group includes
      the immune system-related genes, such as APOBEC2, CALB2, DUSP27, and CXCL11.
      APOBEC2 was positively stained in the epithelium and the peripheral region of the
      germinal center in both tonsils. APOBEC2 expression level was negatively related
      with serum igg level, but did not correlate with clinical course after
      tonsillectomy. CONCLUSION: We confirmed gene expression differences related with
      immune system and muscle structure. The APOBEC2 was confirmed to be elevated in
      the tonsils with IgAN patients, and the gene expression level was negatively
      related with serum igg level in overall patients. These results might be helpful
      to reveal the mechanism of IgAN.

PMID- 20138842
TI  - Distinct developmental expression of two elongase family members in zebrafish.
AB  - Despite the known importance of long-chained polyunsaturated fatty acids (LC
      PUFA) during development, very little is known about their utilization and
      biosynthesis during embryogenesis. Combining the advantages of the existence of a
      complete range of enzymes required for LC-PUFA biosynthesis and the well
      established developmental biology tools in zebrafish, we examined the expression
      patterns of three LC-PUFA biosynthesis genes, Elovl2-like elongase (elovl2),
      Elovl5-like elongase (elovl5) and fatty acyl desaturase (fad) in different
      zebrafish developmental stages. The presence of all three genes in the brain as
      early as 24 hours post fertilization (hpf) implies LC-PUFA synthesis activity in
      the embryonic brain. This expression eventually subsides from 72 hpf onwards,
      coinciding with the initiation of elovl2 and fad expression in the liver and
      intestine, 2 organs known to be involved in adult fish LC-PUFA biosynthesis.
      Collectively, these patterns strongly suggest the necessity for localized
      production of LC-PUFA in the brain during in early stage embryos prior to the
      maturation of the liver and intestine. Interestingly, we also showed a specific
      expression of elovl5 in the proximal convoluted tubule (PCT) of the zebrafish
      pronephros, suggesting a possible new role for LC-PUFA in kidney development and
      function.

PMID- 20138843
TI  - NaCl flux between apical and basolateral side recruits claudin-1 to tight
      junction strands and regulates paracellular transport.
AB  - In multicellular organisms, epithelia separate and divide the internal
      environment maintaining appropriate conditions in each compartment. To maintain
      homeostasis in these compartments, claudins, major cell adhesion molecules in
      tight junctions (TJs), regulate movements of several substances through the
      paracellular pathway (barrier function). In this study, we investigated effects
      of the flux of several substances between apical and basolateral side on
      paracellular transport and TJ protein localization. NaCl flux from apical to
      basolateral side increased paracellular conductance (Gp) and recruited claudin-1
      from lateral cell membrane to the apical end with the colocalization with
      occludin, one of the TJ proteins concentrated at TJ strands. Oppositely-directed
      flux of sucrose against NaCl flux inhibited these reactions and same directional
      flux of sucrose with NaCl enhanced the increase of Gp, whereas 10-kDa dextran
      inhibited these reactions regardless of the side of administration. Our present
      findings indicated that TJ protein localization and barrier function are
      regulated depending on the environmental differences between apical and
      basolateral side.

PMID- 20138844
TI  - Glutamate induces neurotrophic factor production from microglia via protein
      kinase C pathway.
AB  - Microglia are intrinsic immune cells in the central nervous system and play key
      roles in the pathogenesis of various central nervous system disorders. Microglia
      have been shown to attack damaged neurons by secreting a variety of neurotoxic
      factors including inflammatory cytokines, reactive oxygen species and glutamate.
      On the other hand, they can produce neurotrophic factors (NTFs) which support
      neuronal survival and growth. However, the precise mechanism that regulates
      microglial NTF production is not fully understood, and the relation between
      glutamate and NTFs remains unclear. In the present study, we show that glutamate
      significantly induces microglial NTF production by the activation of N-methyl-d
      aspartate (NMDA) receptors, group III metabotropic glutamate receptors, and
      glutamate transporters. Activation of NMDA receptors and group III metabotropic
      glutamate receptors induces intracellular Ca(2+) release from the endoplasmic
      reticulum. Further, stimulation of glutamate transporters leads to influx of
      extracellular Ca(2+) in a Na(+)-dependent manner. This intracellular Ca(2+)
      elevation activates the protein kinase C pathway which induces microglial NTF
      expression and production. These results suggest that microglia play a
      neuroprotective role during the excitotoxic state in neurodegenerative diseases.

PMID- 20138845
TI  - Zinc differentially acts on components of long-term potentiation at hippocampal
      CA1 synapses.
AB  - Long-term potentiation (LTP) at hippocampal CA1 synapses consists of N-methyl-d
      aspartate (NMDA) receptor-dependent and NMDA receptor-independent forms. The
      action of divalent heavy metals, which are NMDA receptor antagonists, was
      examined focusing on the evidence that CA1 LTP induced by a 100-Hz tetanus for 1s
      is abolished in the presence of 2-amino-5-phosphonovalerate (APV), a NMDA
      receptor antagonist. Only ZnCl2 (5microM) of heavy metals tested potentiated CA1
      LTP. CA1 LTP induced by repeated 100-Hz tetanus (1s, 6 times, 10min interval),
      which reached a plateau in magnitude, was abolished in the presence of 50microM
      APV. In this case, CA1 LTP after the first tetanus was potentiated in the
      presence of 5microM ZnCl2, whereas CA1 LTP after the last tetanus was not
      potentiated. These results indicate that the magnitude of NMDA receptor-dependent
      CA1 LTP can be positively shifted with 5microM ZnCl2 in the range of the maximum
      magnitude. CA1 LTP induced by a 200-Hz tetanus for 1s was not potentiated in the
      presence of 5microM ZnCl2 and was partially inhibited in the presence of APV.
      Furthermore, CA1 LTP induced by a 200-Hz tetanus for 1s in the presence of APV
      was not potentiated in the presence of 5microM ZnCl2, indicating that NMDA
      receptor-independent CA1 LTP is not potentiated with 5microM ZnCl2. The present
      study suggests that zinc differentially acts on CA1 LTP components.

PMID- 20138846
TI  - Spinal GABA receptors mediate the suppressive effect of electroacupuncture on
      cold allodynia in rats.
AB  - This study was performed to determine whether spinal GABAergic systems mediate
      the relieving effects of low frequency electroacupuncture (EA) on cold allodynia
      in a rat tail model of neuropathic pain. For neuropathic surgery, the right
      superior caudal trunk was resected at the level between the S1 and S2 spinal
      nerves innervating the tail. Two weeks after the nerve injury, the intrathecal
      catheter was implanted. Five days after the catheterization, rats were
      intrathecally injected with gabazine (GABA(A) receptor antagonist, 0.0003, 0.001
      or 0.003mug), or saclofen (GABA(B) receptor antagonist, 3, 10 or 30mug). Ten
      minutes after the injection, EA (2Hz) was applied to the ST36 acupoint for 30min.
      The cold allodynia was assessed by the tail immersion test (i.e. immersing the
      tail in cold (4 degrees C) water and measuring the latency of an abrupt tail
      movement) before and after the EA treatment. EA stimulation at ST36 significantly
      inhibited the cold allodynia sign, whereas EA at non-acupoint and plain
      acupuncture at ST36 (without electrical stimulation) did not show antiallodynic
      effects. Intrathecal administration of gabazine or saclofen blocked the relieving
      effects of ST36 EA stimulation on cold allodynia. These results suggest that
      spinal GABA(A) and GABA(B) receptors mediate the suppressive effect of low
      frequency EA on cold allodynia in the tail neuropathic rats.

PMID- 20138847
TI  - Properties of gamma frequency oscillatory activity induced in hippocampal slices
      from the adult GAD67-GFP (Deltaneo) mouse.
AB  - The green fluorescent protein (GFP)-linked expression of protein in transgenic
      mice provides an ideal tool for the correlation of structure and function in the
      CNS. An important target of study is the role of GABAergic neurons in oscillatory
      activity in the hippocampus, and this would be facilitated with transgenic mice
      in which GFP is linked to the expression of GABA markers. One such mouse is the
      GAD67-GFP (Deltaneo), and here we compare the properties of kainate- and
      carbachol-induced oscillatory activity generated in CA3 of hippocampal slices
      from heterozygous GAD67-GFP (Deltaneo) mice and wild type litter mates. For both
      paradigms and in both mouse preparations oscillations were generated in the 20
      30Hz range, and for the kainate-, but not the carbachol-induced oscillations,
      there was a small but significant difference in peak frequency of the
      oscillations between GAD67-GFP (Deltaneo) mice (28.4+/-2.2Hz) and wild type mice
      (25+/-1.6Hz). For both oscillatory paradigms there was no significant difference
      between mouse strains in area power of the oscillatory activity in the stratum
      oriens lamina of CA3, but for the kainate-induced oscillations, area power became
      significantly diminished in the stratum radiatum lamina of the GAD67-GFP
      (Deltaneo) mouse compared with the wild type mouse after prolonged exposure to
      kainate. This gradual reduction in area power in CA3 of the transgenic mouse was
      rescued by inclusion of Guvacine, a GABA uptake inhibitor, suggesting that the
      reported lower levels of GABA in the GAD67-GFP (Deltaneo) mouse brain during
      development and in the adult may contribute to a reduction in the efficiency of
      GABA neurotransmission after prolonged stimulation of the GABAergic circuitry.

PMID- 20138848
TI  - Distribution of apoptosis-related proteins in sporadic Creutzfeldt-Jakob disease.
AB  - Apoptosis is one mode of programmed cell death in sporadic Creutzfeldt-Jakob
      disease (sCJD). Distribution of affected brain regions varies between subtypes of
      sCJD. To compare apoptosis-related proteins representing different stages of cell
      death, we evaluated 30 anatomical regions for PARP, NF-kappaB, C-Jun, caspase 3
      and 9, and BAX immunoreactivity in 12 sCJD cases of MM-1, MV-1, VV-2, and MV-2
      subtypes, and 4 control brains. Chi-square test was used to compare the regional
      presence of immunoreactivities in sCJD cases and controls. The total number of
      subregions showing neuronal immunoreactivity for any apoptosis-related protein,
      in particular caspase-3, BAX, and PARP, was significantly higher in sCJD than
      controls, differed between subtypes of sCJD, and inversely correlated with
      duration of illness. Thus, sCJD subtypes are both qualitatively and regionally
      distinct in the predominance of apoptosis-related proteins, confirming regional
      vulnerabilities of sCJD subtypes that potentially reflect distinct responses to
      pathogenetic events.

PMID- 20138849
TI  - Developmental appearance and disappearance of cortical events and oscillations in
      infant rats.
AB  - Until recently, organized and state-dependent neocortical activity in infant rats
      was thought to commence with the emergence of delta waves at postnatal day (P)11.
      This view is changing with the discovery of several forms of cortical activity
      that are detectable soon after birth, including spindle bursts (SBs) and slow
      activity transients (SATs). Here we provide further evidence of surprisingly rich
      cortical activity patterns during early development and document, in P5-P13 rats,
      the appearance, disappearance, and transient expression of three cortical events
      and oscillations. EEG activity in frontal, parietal, and occipital cortices was
      recorded in unanesthetized, head-fixed subjects using 16-channel laminar silicon
      electrodes and Ag-AgCl electrodes. In addition to SATs, we identified two novel
      forms of activity: cortical sharp potentials (CSPs) and gamma bursts (GBs). SBs
      were not observed in these areas. CSPs, defined as discrete, biphasic events with
      a duration of 250 ms, exhibited an inverted-U developmental trajectory with peak
      prevalence at P9. In contrast, GBs, defined as brief bursts of 40-Hz activity,
      increased steadily in prevalence and duration from P5 through P13. The prevalence
      of SATs decreased steadily across the ages tested here. Furthermore, both CSPs
      and GBs were more likely to occur during sleep than during wakefulness. Because
      SATs, CSPs, and GBs exhibit different developmental trajectories and rates of
      occurrence, and can occur independently of each other, they appear to be distinct
      patterns of neuronal activity. We hypothesize that these diverse patterns of
      neurophysiological activity reflect the instantaneous local structure and
      connectivity of the developing neocortex.

PMID- 20138850
TI  - Stress rapidly increases alpha 1d adrenergic receptor mRNA in the rat dentate
      gyrus.
AB  - The hippocampal formation is a highly plastic brain region that is sensitive to
      stress. It receives extensive noradrenergic projections, and noradrenaline is
      released in the hippocampus in response to stressor exposure. The hippocampus
      expresses particularly high levels of the alpha(1D) adrenergic receptor (ADR) and
      we have previously demonstrated that alpha(1d) ADR mRNA expression in the rat
      hippocampus is modulated by corticosterone. One of the defining features of a
      stress response is activation of the hypothalamic pituitary adrenal (HPA) axis,
      resulting in the release of corticosterone from the adrenal glands. However, the
      effect of stress on hippocampal expression of alpha(1d) ADR mRNA has not been
      determined. In this study, male rats were exposed to inescapable tail shock, loud
      noise or restraint, and the effect on alpha(1d) ADR mRNA expression in the
      hippocampus was determined by semi-quantitative in situ hybridization. All three
      stressors resulted in a rapid upregulation of alpha(1d) ADR mRNA in the dentate
      gyrus, with expression peaking at approximately 90min after the start of the
      stressor. Physical activity has previously been reported to counteract some of
      the effects of stress that occur within the dentate gyrus. However, 6weeks of
      voluntary wheel running in rats did not prevent the restraint stress-induced
      increase in alpha(1d) ADR mRNA expression in the dentate gyrus. Although the
      function of the alpha(1D) ADR in the dentate gyrus is not known, these data
      provide further evidence for a close interaction between stress and the
      noradrenergic system in the hippocampus.

PMID- 20138851
TI  - LPS-induced iNOS expression in Bv-2 cells is suppressed by an oxidative mechanism
      acting on the JNK pathway--a potential role for neuroprotection.
AB  - Activated microglia cells, observed during chronic inflammation, produce and
      secrete compounds that at high concentrations or during sustained production
      might cause neuronal cell death. Inducible nitric oxide synthase (iNOS) is
      expressed in response to various immunological stimuli and catalyses the
      formation of the free radical nitric oxide (NO), that at low and regulated levels
      participate in cell signaling and cytoprotective events, whereas its higher and
      unregulated production can promote neurotoxicity in cells or in tissues.
      Regulation of NO production is therefore central for maintaining NO-levels within
      a safe window. We have analyzed iNOS protein expression and NO production, in
      murine microglial Bv-2 cells after 16h treatment with the bacterial endotoxin
      lipopolysaccharide (LPS). We have further analyzed three MAPK pathways, by co
      treating the cells with LPS and the inhibitors of ERK1/2, p38 or JNK MAPK
      activities. To investigate participation of an oxidative regulatory mechanism,
      cells were also treated with the antioxidant N-acetyl-L-cysteine (NAC). Our
      results show that LPS-induced iNOS expression in Bv-2 cells is mainly mediated
      through JNK MAPK. In addition, co-treatment of the Bv-2 cells with LPS and NAC
      surprisingly further increased the iNOS expression, an effect also found to be
      mediated through the JNK MAPK pathway. The level of phosphorylated JNK MAPK (p46)
      was strongly increased by LPS alone and was further increased when combined with
      NAC. Our data indicate that iNOS and NO production are suppressed by an oxidative
      mechanism acting on the JNK MAPK pathway and we speculate that it might
      constitute a potential regulatory mechanism controlling the NO level.

PMID- 20138852
TI  - Cocoa-enriched diets enhance expression of phosphatases and decrease expression
      of inflammatory molecules in trigeminal ganglion neurons.
AB  - Activation of trigeminal nerves and release of neuropeptides that promote
      inflammation are implicated in the underlying pathology of migraine and
      temporomandibular joint (TMJ) disorders. The overall response of trigeminal
      nerves to peripheral inflammatory stimuli involves a balance between enzymes that
      promote inflammation, kinases, and those that restore homeostasis, phosphatases.
      The goal of this study was to determine the effects of a cocoa-enriched diet on
      the expression of key inflammatory proteins in trigeminal ganglion neurons under
      basal and inflammatory conditions. Rats were fed a control diet or an isocaloric
      diet enriched in cocoa for 14days prior to an injection of noxious stimuli to
      cause acute or chronic excitation of trigeminal neurons. In animals fed a cocoa
      enriched diet, basal levels of the mitogen-activated kinase (MAP) phosphatases
      MKP-1 and MKP-3 were elevated in neurons. Importantly, the stimulatory effects of
      acute or chronic peripheral inflammation on neuronal expression of the MAPK p38
      and extracellular signal-regulated kinases (ERK) were significantly repressed in
      response to cocoa. Similarly, dietary cocoa significantly suppressed basal
      neuronal expression of calcitonin gene-related peptide (CGRP) as well as
      stimulated levels of the inducible form of nitric oxide synthase (iNOS), proteins
      implicated in the underlying pathology of migraine and TMJ disorders. To our
      knowledge, this is the first evidence that a dietary supplement can cause
      upregulation of MKP, and that cocoa can prevent inflammatory responses in
      trigeminal ganglion neurons. Furthermore, our data provide evidence that cocoa
      contains biologically active compounds that would be beneficial in the treatment
      of migraine and TMJ disorders.

PMID- 20138853
TI  - Protective effects of pre-germinated brown rice diet on low levels of Pb-induced
      learning and memory deficits in developing rat.
AB  - Lead (Pb) is a known neurotoxicant in humans and experimental animals. Numerous
      studies have provided evidence that humans, especially young children, and
      animals chronically intoxicated with low levels of Pb show learning and memory
      impairments. Unfortunately, Pb-poisoning cases continue to occur in many
      countries. Because the current treatment options are very limited, there is a
      need for alternative methods to attenuate Pb toxicity. In this study, the weaning
      (postnatal day 21, PND21) rats were randomly divided into five groups: the
      control group (AIN-93G diet, de-ionized water), the lead acetate (PbAC) group
      (AIN-93G diet, 2g/L PbAC in de-ionized water), the lead acetate+WR group (white
      rice diet, 2g/L PbAC in de-ionized water; PbAC+WR), the lead acetate+BR group
      (brown rice diet, 2g/L PbAC in de-ionized water; PbAC+BR) and the lead acetate+PR
      group (pre-germinated brown rice diet, 2g/L PbAC in de-ionized water; PbAC+PR).
      The animals received the different diets until PND60, and then the experiments
      were terminated. The protective effects of pre-germinated brown rice (PR) on Pb
      induced learning and memory impairment in weaning rats were assessed by the
      Morris water maze and one-trial-learning passive avoidance test. The anti
      oxidative effects of feeding a PR diet to Pb-exposed rats were evaluated. The
      levels of reactive oxygen species (ROS) were determined by flow cytometry. The
      levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), gamma-aminobutyric acid (GABA) and
      glutamate were determined by HPLC. Our data showed that feeding a PR diet
      decreased the accumulation of lead and decreased Pb-induced learning and memory
      deficits in developing rats. The mechanisms might be related to the anti
      oxidative effects and large amount of GABA in PR. Our study provides a regimen to
      reduce Pb-induced toxicity, especially future learning and memory deficits in the
      developing brain.

PMID- 20138854
TI  - The antidotal efficacy of the bispyridinium oximes K027 and TMB-4 against tabun
      poisoning in mice.
AB  - A toxic effect of highly toxic nervous agents is irreversible inhibition of
      vitally important enzyme acethylcholinesterase (AChE). Inhibition of AChE results
      in accumulation of acetylcholine (ACh) at the synaptic cleft of the cholinergic
      neurons, leading to overstimulation of cholinergic receptors. The highly toxic
      nature of tabun has been known for many years, but there are still serious
      limitations to the antidotal therapy. In this paper a bispyridinium compound K027
      [1-(4-hydroxyiminomethylpyridinium)-3-(-4-carbamoylpyridinium) propane dibromide]
      was tested as potential antidote in tabun poisoned mice. Oxime TMB-4 was included
      for comparison. The therapeutic efficacy of applied antidotal regimens was tested
      as pretreatment given 15 min before tabun poisoning and/or as therapy given 1 min
      after tabun poisoning. Using oxime K027 (25% of its LD(50)) plus atropine as
      both, pretreatment and therapy, we showed that this combination can protect mice
      8 times better than the therapy alone. Under these experimental conditions we
      confirmed good antidotal efficacy of K027. Moreover, its low acute toxicity is as
      much as beneficial effect in contrast to high toxicity of currently used TMB-4.

PMID- 20138855
TI  - The +49A>G CTLA-4 polymorphism is associated with rheumatoid arthritis in Mexican
      population.
AB  - BACKGROUND: The Cytotoxic T lymphocyte antigen (CTLA-4) is one of the major
      susceptibility genes associated with autoimmune diseases. Susceptibility to
      rheumatoid arthritis (RA) is determined by both environmental and genetic
      factors. The genetic contribution approaches 50-60%. The association between RA
      with the +49A>G CTLA-4 polymorphism in the Mexican population was investigated.
      METHODS: The polymerase chain reaction-restriction fragment was used to amplify
      the +49A>G CTLA-4 polymorphism in RA patients and healthy subjects (HS). RESULTS:
      We analyzed the association between the +49A>G CTLA-4 polymorphism and RA. The G
      allele frequency was higher in RA patients than HS (46.8 vs 37.7%, OR=1.45,
      p=0.01). RA patients carrying the A/G genotype were significantly more likely to
      be positive to CRP and RF. There was no evidence of an association between SNP
      genotypes and the clinical characteristics of rheumatoid arthritis. CONCLUSIONS:
      The +49A>G CTLA-4 polymorphism is a genetic marker of susceptibility for RA in
      western Mexican population.

PMID- 20138856
TI  - High resolution melting analysis facilitates mutation screening of ETFDH gene:
      applications in riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.
AB  - BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) or gluaric aciduria
      type II is an autosomal recessive disease caused by defects in mitochondrial
      electron transfer system and metabolism of fatty acid. Recently, ETFDH mutations
      were reported to be major causes of riboflavin-responsive MADD. The present study
      is aimed at screening ETFDH mutations. METHODS: High resolution melting (HRM)
      analysis was performed to screen ETFDH mutations. Genomic DNA was extracted from
      peripheral blood samples of the 9 patients with MADD and normal controls. Total
      13 exons of ETFDH were screened by HRM analysis. The results were subsequently
      confirmed by direct DNA sequencing. RESULTS: This diagnostic strategy proved to
      be feasible in detecting 3 known (c.250G>A, c380T>A, c.524G>T) and 1 novel
      (c.1831G>A) ETFDH mutations. Each mutation could be readily and accurately
      identified in the difference plot curves. We estimated the carrier frequency of
      the hotspot mutation, c.250G>A, in the Taiwanese population to be 1:125 (0.8%).
      CONCLUSIONS: HRM analysis can be successfully applied to screen ETFDH mutations.
      Since riboflavin-responsive MADD is often treatable, especially with mutations in
      ETFDH, identifying ETFDH mutations is crucial for these patients.

PMID- 20138857
TI  - Therapeutic drug monitoring of topiramate by liquid chromatography-tandem mass
      spectrometry.
AB  - BACKGROUND: Topiramate (TPM) is a new antiepileptic drug (AED) used worldwide in
      patients with various types of epilepsies and also for prophylaxis of migraine. A
      rapid, selective, reliable, precise, accurate, and reproducible tandem mass
      spectrometric (MS/MS) method for quantification of TPM in human plasma using
      topiramate-d12 as an internal standard (IS) has been developed and validated to
      be used routinely for TDM of TPM. METHODS: The drug and IS were extracted by
      ether and analyzed on Symmetry C18 column. Quantitation was achieved using ESI
      interface employing MRM mode. RESULTS: The method was validated over the
      concentration range of 0.5-30 microg/ml (r>0.99). Intra- and inter-run precisions
      of TPM assay at three concentrations ranged from 0.7 to 7.8% with accuracy (bias)
      varied from -10.0 to 2.1% indicating good precision and accuracy. Analytical
      recoveries of TPM and IS from spiked human plasma were in the range of 84.1 to
      90.0% and 90.0 to 111.0%, respectively. Stability of TPM in human plasma samples
      at different conditions showed that the drug was stable under the studied
      conditions. Matrix effect study showed a lack of matrix effect on mass ions of
      TPM and IS. CONCLUSION: The described method compared well when assessed by
      Heathcontrol TDM theme program (r>0.99). The suitability of the developed method
      for TDM was demonstrated by measuring TPM in human plasma samples of epileptic
      patients treated with TPM. The proposed method is appropriate for routine TDM of
      TPM.

PMID- 20138858
TI  - Identification of orcinol reactive substance in pleural fluid cell lysate--a new
      parameter for classification of pleural effusion.
AB  - BACKGROUND: Cell-free DNA is observed to be more in exudative pleural effusions.
      Based on this fact development of a clinical chemistry test for classification of
      pleural effusion will require DNA extraction followed by PCR amplification and
      electrophoresis. These procedures may not be cost effective for the purpose for
      classification of pleural effusion as already established parameters are popular
      for the purpose which can be estimated by comparatively low cost colorimetric
      procedures. Therefore development of a simple colorimetric test for the
      classification of pleural fluid based on nucleic acid identification test can be
      attempted. The aim of this work is to develop such colorimetric test for
      classification of pleural effusion using only pleural fluid sample. METHODS: Cell
      pellet is obtained from 5 ml pleural fluid which is lysed and subjected to DNA
      extraction, followed by identification under UV-transilluminator after
      electrophoresis and orcinol and diphenylamine reaction. RESULT: Exudates show
      extractable DNA from 5 ml biofluid (n=52) which are not observed from transudate
      (n=32). Orcinol reaction is significantly positive in exudates (n=52) compared to
      the transudates (n=32). Diphenylamine test cannot differentiate exudate from
      transudate. CONCLUSION: Orcinol reaction of cell lysate obtained from pleural
      fluid can classify pleural fluid sample into exudate or transudate.

PMID- 20138859
TI  - Association between genetic polymorphisms of the NPHS1 gene and membranous
      glomerulonephritis in the Taiwanese population.
AB  - BACKGROUND: Membranous glomerulonephritis (MGN) is one of the most common causes
      of nephrotic syndrome in adults. NPHS1 encoding nephrin is a transmembrane
      protein of the immunoglobulin family. We clarified the relationship between NPHS1
      gene polymorphisms and the susceptibility or progression of MGN. METHODS: We
      recruited a cohort of 132 biopsy-diagnosed MGN patients and 257 healthy subjects.
      Genotyping of three SNPs (rs401824, rs437168 and rs3814995) at chromosome
      positions 41034749 (5'UTR), 41026259(exon17) and 41034052 (exon 3) was performed
      using a Taqman SNP genotyping assay. RESULTS: There was a significant difference
      in genotype frequency distribution of rs437168 polymorphism between MGN patients
      and controls. The results also showed that the frequency of the G allele was
      significantly higher in the patient group. Among the polymorphisms rs437168,
      rs401824 and rs3814995, no significant haplotype was shown in MGN patients. A
      stratified analysis revealed that a high disease progression in the AA genotype
      of rs401824 and GG genotype of rs437168 patients were associated with a low rate
      of remission. CONCLUSIONS: The presence of the different genotypes of NPHS1 was
      associated with susceptibility of MGN and the remission of proteinuria during
      disease progression after the therapy.

PMID- 20138860
TI  - MMP-2 and TIMP-2 gene polymorphisms and susceptibility to atrial fibrillation in
      Chinese Han patients with hypertensive heart disease.
AB  - BACKGROUND: MMP-2 and TIMP-2 play important roles in the pathogenesis of
      arrhythmogenic atrial remodeling, and may contribute to the development and
      persistence of atrial fibrillation (AF). Functional polymorphisms in the promoter
      of MMP-2 and TIMP-2 gene may modulate an individual's susceptibility to AF.
      METHODS: A total of 881 hypertensive heart disease patients from Chinese Han
      population (128 with and 753 without AF) were recruited in this study. The
      genotypes of the MMP2-1306C>T and -735C>T polymorphisms and TIMP-2 -418G>C
      polymorphisms were determined using PCR based method. The plasma concentration of
      TIMP-2 was measured by enzyme-linked immunosorbent assay in a subgroup with 81
      patients. RESULTS: Both genotype distribution and allele frequency of the TIMP-2 
      418G>C polymorphism were significantly different between the AF and control group
      (P=0.005 and P=0.001, respectively). The C allele carriers (GC+CC) had a
      significantly increased risk of AF compared with the GG homozygotes (odds
      ratio,1.77, 95% CI 1.21-2.92, P=0.009) in a logistic regression model after
      adjustment for age, left atrial dimension, left ventricular mass index, and
      antihypertensive drugs. The C allele carriers also had reduced levels of plasma
      TIMP-2 levels compared with GG homozygotes in both AF patients and control
      subjects. No relationship was found in this cohort between the presence of the
      MMP-2 -1306C>T and -735C>T polymorphism and AF. CONCLUSIONS: The TIMP-2 -418G>C
      polymorphism is significantly associated with an increased susceptibility to AF
      in Chinese Han patients with hypertensive heart disease. The -418C allele, which
      is associated with a decreased expression of TIMP-2, might be a genetic risk for
      the development of AF in this cohort.

PMID- 20138861
TI  - The polarity protein Pard3 is required for centrosome positioning during
      neurulation.
AB  - Microtubules are essential regulators of cell polarity, architecture and
      motility. The organization of the microtubule network is context-specific. In non
      polarized cells, microtubules are anchored to the centrosome and form radial
      arrays. In most epithelial cells, microtubules are noncentrosomal, align along
      the apico-basal axis and the centrosome templates a cilium. It follows that cells
      undergoing mesenchyme-to-epithelium transitions must reorganize their microtubule
      network extensively, yet little is understood about how this process is
      orchestrated. In particular, the pathways regulating the apical positioning of
      the centrosome are unknown, a central question given the role of cilia in fluid
      propulsion, sensation and signaling. In zebrafish, neural progenitors undergo
      progressive epithelialization during neurulation, and thus provide a convenient
      in vivo cellular context in which to address this question. We demonstrate here
      that the microtubule cytoskeleton gradually transitions from a radial to linear
      organization during neurulation and that microtubules function in conjunction
      with the polarity protein Pard3 to mediate centrosome positioning. Pard3
      depletion results in hydrocephalus, a defect often associated with abnormal
      cerebrospinal fluid flow that has been linked to cilia defects. These findings
      thus bring to focus cellular events occurring during neurulation and reveal novel
      molecular mechanisms implicated in centrosome positioning.

PMID- 20138862
TI  - Inhibition of brain [(3)H]cimetidine binding by improgan-like antinociceptive
      drugs.
AB  - [(3)H]cimetidine, a radiolabeled histamine H(2) receptor antagonist, binds with
      high affinity to an unknown hemoprotein in the brain which is not the histamine
      H(2) receptor. Improgan, a close chemical congener of cimetidine, is a highly
      effective pain-relieving drug following CNS administration, yet its mechanism of
      action remains unknown. To test the hypothesis that the [(3)H]cimetidine-binding
      site is the improgan antinociceptive target, improgan, cimetidine, and 8 other
      chemical congeners were studied as potential inhibitors of [(3)H]cimetidine
      binding in membrane fractions from the rat brain. All compounds produced a
      concentration-dependent inhibition of [(3)H]cimetidine binding over a 500-fold
      range of potencies (K(i) values were 14.5 to >8000nM). However, antinociceptive
      potencies in rats did not significantly correlate with [(3)H]cimetidine-binding
      affinities (r=0.018, p=0.97, n=10). These results suggest that the
      [(3)H]cimetidine-binding site is not the analgesic target for improgan-like
      drugs.

PMID- 20138863
TI  - Changes in the somatostatin (SOM)-like immunoreactivity within nervous structures
      of the porcine descending colon under various pathological factors.
AB  - This study reports on changes in the somatostatin-like immunoreactive (SOM-LI)
      nerve structures of the enteric nervous system (ENS) in the porcine descending
      colon, caused by chemically driven inflammation, proliferative enteropathy (PE),
      which is a "natural" inflammation with proliferative changes and nerve injury
      (axotomy). The distribution pattern of SOM-LI structures was studied using the
      immunofluorescence technique in the circular muscle layer, the myenteric (MP),
      outer submucous (OSP) and inner submucous plexuses (ISP) and also in the mucosal
      layer. Under physiological conditions SOM-LI perikarya have been shown to
      constitute 1.97+/-0.36%, 2.06+/-0.33% and 4.23+/-0.40% in the MP, OSP and ISP,
      respectively. Changes in SOM-immunoreactivity depended on the pathological factor
      and the part of the ENS studied. Numbers of the SOM-LI perikarya amounted 1.81+/
      0.30, 1.97+/-0.24 and 11.15+/-0.95 during chemically induced colitis and 3.21+/
      0.37%, 4.33+/-0.33% and 4.42+/-0.32% after axotomy in MP, OSP and ISP,
      respectively. Moreover during PE SOM-positive cell bodies were not observed at
      all in MP, whereas within OSP and ISP the number of SOM-LI perikarya amounted to
      3.34+/-0.36 and 10.92+/-059, respectively. All processes studied resulted in a
      decrease in the number of SOM-LI nerve fibers in the mucosal layer, whereas
      within the circular muscle layer chemically induced inflammation and axotomy
      caused an increase in the number of the SOM-LI nerve fibers contrary to PE, which
      reduced the number of such fibers. The obtained results suggest that SOM-LI nerve
      structures of the ENS may participate in various pathological states within the
      porcine descending colon and their functions probably depend on the type of
      pathological factor.

PMID- 20138866
TI  - Detection of matrix metallopeptidase-9-like proteins in Trypanosoma cruzi.
AB  - In this study, the cell-associated and extracellular peptidases of Trypanosoma
      cruzi grown in modified Roitman's complex (MRC) medium were analyzed by measuring
      peptidase activity in gelatin-containing zymograms. Our results showed that the
      cell-associated peptidases as well as peptidases extracellularly released by T.
      cruzi displayed two distinct proteolytic classes: cysteine and metallopeptidase
      activities. The major cysteine peptidase, cruzipain, synthesized by T. cruzi
      cells was detected in cellular parasite content, as a 50kDa reactive polypeptide,
      after probing with anti-cruzipain antibody. In addition, metallo-type peptidases
      belonging to the matrix metallopeptidase-9 (MMP-9) family were revealed, after
      Western blotting, as a 97kDa protein band in cellular extract and an 85kDa
      polypeptide in both cellular and secreted parasite extracts. The MMP-9-like
      activity present in cells and spent culture medium was immunoprecipitated by an
      anti-MMP-9 polyclonal antibody. The surface location of MMP-9-like proteins in T.
      cruzi was also evidenced by means of flow cytometry analysis. Furthermore,
      doxycycline that has direct MMP-9 inhibiting properties in vitro, inhibited MMP-9
      like activities in gel zymography, immunoprecipitation and flow cytometry
      analyses. This is the first report of the presence of MMP-9-like molecules in T.
      cruzi. The presence of a matrix extracellular-degrading enzyme may play a role in
      the T. cruzi-host cell interaction, making this enzyme a potential target for
      future drug development against this pathogenic trypanosomatid.

PMID- 20138864
TI  - Cross-regulation of signaling pathways: an example of nuclear hormone receptors
      and the canonical Wnt pathway.
AB  - Predicting the potential physiological outcome(s) of any given molecular pathway
      is complex because of cross-talk with other pathways. This is particularly
      evident in the case of the nuclear hormone receptor and canonical Wnt pathways,
      which regulate cell growth and proliferation, differentiation, apoptosis, and
      metastatic potential in numerous tissues. These pathways are known to intersect
      at many levels: in the intracellular space, at the membrane, in the cytoplasm,
      and within the nucleus. The outcomes of these interactions are important in the
      control of stem cell differentiation and maintenance, feedback loops, and
      regulating oncogenic potential. The aim of this review is to demonstrate the
      importance of considering pathway cross-talk when predicting functional outcomes
      of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as
      an example.

PMID- 20138865
TI  - Localization and function of GABA transporters in the globus pallidus of
      parkinsonian monkeys.
AB  - The GABA transporters GAT-1 and GAT-3 are abundant in the external and internal
      segments of the globus pallidus (GPe and GPi, respectively). We have shown that
      pharmacological blockade of either of these transporters results in decreased
      neuronal firing, and in elevated levels of extracellular GABA in normal monkeys.
      We now studied whether the electrophysiologic and biochemical effects of local
      intra-pallidal injections of GAT-1 and GAT-3 blockers, or the subcellular
      localization of these transporters, are altered in monkeys rendered parkinsonian
      by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The
      subcellular localization of the transporters in GPe and GPi, studied with
      electron microscopy immunoperoxidase, was similar to that found in normal
      animals: i.e., GAT-3 immunoreactivity was mostly confined to glial processes,
      while GAT-1 labeling was expressed in unmyelinated axons and glial processes. A
      combined injection/recording device was used to record the extracellular activity
      of single neurons in GPe and GPi, before, during and after administration of
      small volumes (1microl) of either the GAT-1 inhibitor, SKF-89976A hydrochloride
      (720ng), or the GAT-3 inhibitor, (S)-SNAP-5114 (500ng). In GPe, the effects of
      GAT-1 or GAT-3 blockade were similar to those seen in normal monkeys. However,
      unlike the findings in the normal state, the firing of most neurons was not
      affected by blockade of either transporter in GPi. These results suggest that,
      after dopaminergic depletion, the functions of GABA transporters are altered in
      GPi; without major changes in their subcellular localization.

PMID- 20138867
TI  - Entamoeba histolytica: expression and localization of Gal/GalNAc lectin in
      virulent and non-virulent variants from HM1:IMSS strain.
AB  - We have purified Gal/GalNAc lectin from Entamoeba histolytica by electroelution.
      The purified protein was used to immunize rabbits and obtain polyclonal IgG's
      anti-lectin. These antibodies were used as tools to analyze the expression and
      localization of the amoebic lectin in both virulent (vEh) and non-virulent (nvEh)
      variants of axenically cultured HM1:IMSS strain. vEh is able to induce liver
      abscesses in hamsters, whereas nvEh has lost this ability. In vitro, amoebic
      trophozoites from both variants equally express this protein as shown by
      densitometric analysis of the corresponding band in Western blots from lysates.
      In both types of trophozoites, the pattern of distribution of the lectin was
      mainly on the surface. We have also compared by immunohistochemistry the presence
      and distribution of lectin in the in vivo liver lesions produced in hamsters. In
      order to prolong the survival of nvEh to analyze both variants in an in vivo
      model, hamsters inoculated with nvEh were treated with methyl prednisolone. Our
      results suggest that the Gal/GalNAc lectin is equally expressed in both nvEh and
      vEh.

PMID- 20138868
TI  - Eimeria tenella: effects of diclazuril treatment on microneme genes expression in
      second-generation merozoites and pathological changes of caeca in parasitized
      chickens.
AB  - The effects of diclazuril on mRNA expression levels of invasion-related microneme
      genes were examined in second-generation merozoites of Eimeria tenella (E.
      tenella) by quantitative real-time (QRT) PCR. Diclazruil treatment of infected
      chickens significantly decreased the number of second-generation merozoites by
      65.13%, and resulted in downregulation of EtMIC genes: EtMIC1 by 65.63%, EtMIC2
      by 64.12%, EtMIC3 by 56.82%, EtMIC4 by 73.48%, and EtMIC5 by 78.17%. SEM images
      of caecum tissue from uninfected chickens showed regular intestinal villus
      structure. In infected chickens, a distinct loss of the superficial epithelium,
      with a flattened mucosa and large-area necrosis and anabrosis, was evident. In
      diclazruil-treated chickens, a decrease in merozoite number and a visibly
      improved appearance of the caeca were noted. These improvements appeared to be
      mediated in part by downregulation of the expression of invasion-related EtMIC
      genes in response to diclazuril.

PMID- 20138869
TI  - Molecular characterization of a truncated antigen (Wb14) of SXP-1 of Wuchereria
      bancrofti from four endemic regions in India.
AB  - Wb14 of Wuchereria bancrofti, an orthologue of Brugia malayi SXP-1 and W.
      bancrofti SXP-1, was amplified from genomic DNA of W. bancrofti microfilaria
      collected from four distant geographical locations in India viz., Vellore,
      Bhubaneshwar, Pondicherry and Sevagram. The gene was sub-cloned in a prokaryotic
      vector pRSET and expressed in Escherichia coli as a truncated protein
      (approximately 23kDa). The nucleotide sequence of the gene is 98% similar to that
      of WbSXP-1 and is found to be intron-less. However, the analysis and comparison
      of the derived amino acid sequence with WbSXP-1 showed that Wb14 is truncated at
      amino acid position 153. The distribution of the two genes in the studied four
      geographical locations indicated that WbSXP-1 is prevalent only in parasite
      samples from Sevagram while Wb14 is present in parasites from all the other
      locations. Only a limited polymorphism was observed in both the genes among the
      parasites from different geographical locations.

PMID- 20138870
TI  - Acanthamoeba castellanii: in vitro effects of selected biological, physical and
      chemical factors.
AB  - Trophozoites and cysts of free-living Acanthamoeba castellanii present a serious
      risk to human health as causative agents of human diseases such as fatal
      granulomatous amoebic encephalitis and Acanthamoeba keratitis that is reported
      from various part of the world, also in Poland, with increasing frequency,
      particularly in the contact lens wearers. The amphizoic amoebae are generally
      extremely resistant to different chemical agents, however, several
      strains/isolates within A. castellanii may differ in virulence. Among the
      features considered as associated with the amoeba pathogenicity, temperature
      tolerance and resistance to different environmental conditions are reported. In
      the present study, A. castellanii strain cultured in 26 degrees C after several
      year passages were tested for sensibility/tolerance to instant temperature
      changes as well as exposition to deuterium oxide, D2O. Significant decrease of
      number of viable amoebae during in vitro exposition to D2O occurred, but no
      changes in trophozoites/cysts ratio. The ability of the strain examined to
      develop in higher temperature may indicate a wide adaptation reserve and its
      pathogenic potential.

PMID- 20138871
TI  - Transovarial passage of Leishmania infantum kDNA in artificially infected
      Rhipicephalus sanguineus.
AB  - Phlebotomine sand flies are the only proven biological vectors of Leishmania
      parasites. However, Rhipicephalus sanguineus ticks have long been suspected to
      transmit Leishmania infantum in studies carried out in laboratory and natural
      conditions. In the present study, 5 microl of L. infantum promastigotes (1x10(6)
      cells per ml) was injected into the hemocel through the coxa I of four engorged
      females (F1, F2, F3 and F4). Control ticks (F5 and F6) were injected with sterile
      phosphate-buffered saline (PBS) using the same procedure. Then, these females,
      their eggs, and the originated larvae were tested by real time polymerase chain
      reaction (real-time PCR) for the presence of L. infantum kinetoplast DNA (kDNA).
      Females and eggs were tested after the end of the oviposition period (about 5
      weeks post-inoculation) whereas larvae were tested about 4 months after the
      inoculation of females. All artificially infected females were positive for L.
      infantum kDNA. In addition, two pools of eggs (one from F2 and other from F4) and
      four pools of larvae (one from each F1 and F4 and two from F2) were positive for
      L. infantum kDNA. These results showed, for the first time, the transovarial
      passage of L. infantum kDNA in R. sanguineus ticks, thus suggesting that the
      transovarial transmission of L. infantum protozoa in ticks is worth to be
      investigated.

PMID- 20138872
TI  - Entamoeba histolytica: molecular cloning and characterization of a novel neutral
      sphingomyelinase.
AB  - A novel neutral sphingomyelinase (nSMase) was characterized in Entamoeba
      histolytica trophozoites. SMase, a sphingomyelin-specific form of phospholipase
      C, catalyzes the hydrolysis of sphingomyelin to ceramide and phosphorylcholine.
      Three amebic putative nSMase genes were found to be actively transcribed. Mg(2+)
      independent nSMase activity in the soluble fraction of the trophozoites was
      stimulated by Mn(2+) and partially inhibited by Zn(2+). nSMase activity of the
      recombinant protein EhnSM1, increased 4.5-fold in the presence of 0.5mM Mn(2+),
      and abolished by 5mM Zn(2+). A dose-dependent inhibition of rEhnSM1 was observed
      with scyphostatin, a specific inhibitor of nSMases. The EhnSM1 and EhnSM3 were
      detected in the soluble fraction of the amebic lysate as 35-37kDa proteins by
      western blot analysis. Immunofluorescence assay showed that the overexpressed HA
      tagged EhnSM1 and EhnSM3 were localized to the cytosol. The biological role of
      these novel E. histolytica nSMases described in this work remains to be
      determined.

PMID- 20138873
TI  - Inflammatory changes in the central nervous system are associated with behavioral
      impairment in Plasmodium berghei (strain ANKA)-infected mice.
AB  - Experimental cerebral malaria is a neuroinflammatory condition that results from
      the host immune response to the parasite. Using intravital microscopy, we
      investigated leukocyte recruitment in the brain microcirculation and the temporal
      relationship of this process to the behavioral changes observed in Plasmodium
      berghei (strain ANKA)-infected C57Bl/6 mice. We found that leukocyte recruitment
      was increased from day 5 post-infection (p.i.) onwards. Histopathological changes
      and increased levels of inflammatory cytokines in the brain were also observed.
      Behavioral performance evaluated by the SHIRPA protocol showed functional
      impairment from day 6 p.i. onwards. Thus, early leukocyte migration into the
      brain and associated inflammatory changes may be involved in neurological
      impairment in parasite-infected C57Bl/6 mice.

PMID- 20138874
TI  - Regulation of immunity to Plasmodium: implications from mouse models for blood
      stage malaria vaccine design.
AB  - Malaria, a disease caused by the protozoan parasite Plasmodium, remains a serious
      healthcare problem in developing countries worldwide. While the host-parasite
      relationship in humans has been difficult to determine, the pliability of murine
      malaria models has enabled valuable contributions to the understanding of the
      pathogenesis of disease. Although no single model reflects precisely malaria
      infection of the human, different models collectively provide important
      information on the mechanisms of protective immunity and immunopathogenesis. This
      review summarizes progress towards understanding the broad spectrum of immune
      responsiveness to the blood stages of the malaria parasite during experimental
      infections in mice and highlights how examination of murine malarias sheds light
      on the factors involved in the modulation of vaccine-potentiated immunity.

PMID- 20138875
TI  - Trypanosoma evansi: cholinesterase activity in acutely infected Wistar rats.
AB  - The aim of this study was to evaluate cholinesterase activity during the early
      acute phase of Trypanosoma evansi infection in rats. Fifteen male Wistar rats
      were randomly distributed into three groups (n=5 animals per group): two
      trypanosome-infected groups (T3 and T5) and uninfected controls (C). The animals
      were inoculated intraperitoneally with 10(6) trypanosomes. The blood was
      collected by cardiac puncture on the 3rd (T3) or 5th day post-infection (T5 and
      C). Cerebrum and cerebellum were removed for the evaluation of
      acetylcholinesterase (AChE) activity. AChE activity was also evaluated in whole
      blood and butyrylcholinesterase activity (BUChE) in plasma samples. Parasitemia
      were progressive increase and parasites were observed in the peripheral blood of
      all infected animals one day post-inoculation. AChE activity was not altered in
      cerebrum and cerebellum tissues. AChE activity in blood significantly decreased
      in the T3 and T5 groups (26.63 and 25.86mU/lmolHb) compared with the control
      (37.84mU/lmolHb). In addition BUChE activity in plasma was lower in the T3
      (7.01micromol BTC hydrolyzed/h/mL) than the T5 and C groups (9.84 and
      12.00micromol BTC hydrolyzed/h/mL). This study therefore, shows that reductions
      in the activity of cholinesterase occur in acute infection by T. evansi in rats
      and this demonstrates an important change occurring in animals infected by the
      protozoan and may indicate a potential role the enzymes play in the mechanism of
      disease.

PMID- 20138876
TI  - Ectopic recombination in the central and peripheral nervous system by aP2/FABP4
      Cre mice: implications for metabolism research.
AB  - aP2-Cre mice have amply been used to generate conditional adipose selective
      inactivation of important signaling molecules. We show that the efficiency of Cre
      mediated recombination in adipocytes and adipose selectivity is not always
      guaranteed. In particular, Cre activity was found in ganglia of the peripheral
      nervous system (PNS), in adrenal medulla and in neurons throughout the central
      nervous system (CNS). Because these tissues have an important impact on adipose
      tissue, care should be taken when using aP2-Cre mice to define the role of the
      targeted genes in adipose tissue function.

PMID- 20138877
TI  - Myeloid translocation gene 16b is a dual A-kinase anchoring protein that
      interacts selectively with plexins in a phospho-regulated manner.
AB  - The myeloid translocation gene (MTG) homologue Nervy associates with PlexinA on
      the plasma membrane, where it functions as an A-kinase anchoring protein (AKAP)
      to modulate plexin-mediated semaphorin signaling in Drosophila. Mammalian MTG16b
      is an AKAP found in immune cells where plexin-mediated semaphorin signaling
      regulates immune responses. This study provides the first evidence that MTG16b is
      a dual AKAP capable of binding plexins. These interactions are selective
      (PlexinA1 and A3 bind MTG, while PlexinB1 does not) and can be regulated by PKA
      phosphorylation. Collectively, these data suggest a possible mechanism for the
      targeting and integration of adenosine 3',5'-cyclic monophosphate (cAMP) and
      semaphorin signaling in immune cells.

PMID- 20138878
TI  - Generating artificial homologous proteins according to the representative family
      character in molecular mechanics properties--an attempt in validating an
      underlying rule of protein evolution.
AB  - The molecular mechanics property is the foundation of many characters of
      proteins. Based on intramolecular hydrophobic force network, the representative
      family character underlying a protein's mechanics property is described by a
      simple two-letter scheme. The tendency of a sequence to become a member of a
      protein family is scored according to this mathematical representation. Remote
      homologs of the WW-domain family could be easily designed using such a
      mechanistic signature of protein homology. Experimental validation showed that
      nearly all artificial homologs have the representative folding and bioactivity of
      their assigned family. Since the molecular mechanics property is the only
      consideration in this study, the results indicate its possible role in the
      generation of new members of a protein family during evolution.

PMID- 20138879
TI  - Oxysterol represses high-affinity IgE receptor-stimulated mast cell activation in
      Liver X receptor-dependent and -independent manners.
AB  - Oxysterols activating liver X receptors (LXRs) repress expression of pro
      inflammatory genes and have anti-inflammatory effects. Here, we show for the
      first time that bone marrow-derived murine mast cells (BMMCs) predominantly
      express LXRbeta. 25-hydroxycholesterol, a representative LXR activating
      oxysterol, suppressed IL-6 production and degranulation response in BMMCs
      following engagement of high-affinity IgE receptor (FcepsilonRI). Interestingly,
      25-hydroxycholesterol reduced cell-surface FcepsilonRI expression by inhibiting
      assembly of FcepsilonRIalpha and FcepsilonRIbeta. We demonstrate that LXR
      activation was involved in the suppression of IL-6 production in BMMCs, but that
      reduced FcepsilonRI expression and degranulation response was mediated in an LXR
      independent manner.

PMID- 20138880
TI  - A molecular mechanism for proton-dependent gating in KcsA.
AB  - Activation gating in KcsA is elicited by changes in intracellular proton
      concentration. Thompson et al. identified a charge cluster around the inner gate
      that plays a key role in defining proton activation in KcsA. Here, through
      functional and spectroscopic approaches, we confirmed the role of this charge
      cluster and now provide a mechanism of pH-dependent gating. Channel opening is
      driven by a set of electrostatic interactions that include R117, E120 and E118 at
      the bottom of TM2 and H25 at the end of TM1. We propose that electrostatic
      compensation in this charge cluster stabilizes the closed conformation at neutral
      pH and that its disruption at low pH facilitates the transition to the open
      conformation by means of helix-helix repulsion.

PMID- 20138881
TI  - Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides
      insight into combined deficiency of factor V and factor VIII.
AB  - LMAN1 is a glycoprotein receptor, mediating transfer from the ER to the ER-Golgi
      intermediate compartment. Together with the co-receptor MCFD2, it transports
      coagulation factors V and VIII. Mutations in LMAN1 and MCFD2 can cause combined
      deficiency of factors V and VIII (F5F8D). We present the crystal structure of the
      LMAN1/MCFD2 complex and relate it to patient mutations. Circular dichroism data
      show that the majority of the substitution mutations give rise to a disordered or
      severely destabilized MCFD2 protein. The few stable mutation variants are found
      in the binding surface of the complex leading to impaired LMAN1 binding and
      F5F8D.

PMID- 20138882
TI  - The SLO3 sperm-specific potassium channel plays a vital role in male fertility.
AB  - Here we show a unique example of male infertility conferred by a gene knockout of
      the sperm-specific, pH-dependent SLO3 potassium channel. In striking contrast to
      wild-type sperm which undergo membrane hyperpolarization during capacitation, we
      found that SLO3 mutant sperm undergo membrane depolarization. Several defects in
      SLO3 mutant sperm are evident under capacitating conditions, including impaired
      motility, a bent "hairpin" shape, and failure to undergo the acrosome reaction
      (AR). The failure of AR is rescued by valinomycin which hyperpolarizes mutant
      sperm. Thus SLO3 is the principal potassium channel responsible for capacitation
      induced hyperpolarization, and membrane hyperpolarization is crucial to the AR.

PMID- 20138883
TI  - Swa2p-dependent clathrin dynamics is critical for Flo11p processing and 'Mat'
      formation in the yeast Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae is able to form complex multicellular
      structures called mats on low-density agar Petri plates. Mat formation strictly
      depends on Flo11p, a cell surface mannoprotein that mediates the adhesion of
      yeast cells to the agar surface. Here, we show that Swa2p, an auxilin ortholog
      required for clathrin-coated vesicle uncoating, is strictly required for biofilm
      formation. We show that the maturation and cellular levels of Flo11p are affected
      in Deltaswa2 cells, yet without compromising invasive growth. Both the TPR and J
      domains of Swa2p, but not its clathrin-binding and ubiquitin-association motifs,
      are required for its function in Flo11p processing.

PMID- 20138884
TI  - Vertebrate beta-thymosins: conserved synteny reveals the relationship between
      those of bony fish and of land vertebrates.
AB  - Using conservation of synteny I show how the four thymosins expressed by teleost
      fish are related to the three of tetrapods, which is not evident from their
      protein sequences. This clarification was aided by identification of a novel
      thymosin of reptilians that replaces the beta10 thymosin of mammals. Recent
      reconstruction of the ancestral vertebrate genome suggests that divergence of
      beta-thymosins began with duplication preceding the two rounds of whole genome
      duplication.

PMID- 20138885
TI  - Arginine vasopressin prevents against Abeta(25-35)-induced impairment of spatial
      learning and memory in rats.
AB  - Amyloid beta protein (Abeta) is thought to be responsible for loss of memory in
      Alzheimer's disease (AD). A significant decrease in [Arg(8)]-vasopressin (AVP)
      has been found in the AD brain and in plasma; however, it is unclear whether this
      decrease in AVP is involved in Abeta-induced impairment of spatial cognition and
      whether AVP can protect against Abeta-induced deficits in cognitive function. The
      present study examined the effects of intracerebroventricular (i.c.v.) injection
      of AVP on spatial learning and memory in the Morris water maze test and
      investigated the potential protective function of AVP against Abeta-induced
      impairment in spatial cognition. The results were as follows: (1) i.c.v.
      injection of 25 nmol Abeta(25-35) resulted in a significant decline in spatial
      learning and memory; (2) 1 nmol and 10 nmol, but not 0.1 nmol, AVP injections
      markedly improved learning and memory; (3) pretreatment with 1 nmol or 10 nmol,
      but not 0.1 nmol, AVP effectively reversed the impairment in spatial learning and
      memory induced by Abeta(25-35); and (4) none of the drugs, including Abeta(25-35)
      and different concentrations of AVP, affected the vision or swimming speed of the
      rats. These results indicate that Abeta(25-35) could significantly impair spatial
      learning and memory in rats, and pretreatment with AVP centrally can enhance
      spatial learning and effectively prevent the behavioral impairment induced by
      neurotoxic Abeta(25-35). Thus, the present study provides further insight into
      the mechanisms by which Abeta impairs spatial learning and memory, suggesting
      that up-regulation of central AVP might be beneficial in the prevention and
      treatment of AD.

PMID- 20138886
TI  - Transient expression of specific Cotesia plutellae bracoviral segments induces
      prolonged larval development of the diamondback moth, Plutella xylostella.
AB  - A polydnavirus, Cotesia plutellae bracovirus (CpBV), possesses a segmented and
      dispersed genome that is located on chromosome(s) of its symbiotic endoparasitic
      wasp, C. plutellae. When the host wasp parasitizes larvae of the diamondback
      moth, Plutella xylostella, at least 27 viral genome segments are delivered to the
      parasitized host along with the wasp egg. The parasitized P. xylostella exhibits
      significant immunosuppression and a prolonged larval development. Parasitized
      larvae take about 2 days longer than nonparasitized larvae to develop until the
      wandering stage of the final larval instar, and die after egress of the full
      grown wasp larvae. Developmental analysis using juvenile hormone and ecdysteroid
      analogs suggests that altering endocrine signals could induce the retardation of
      larval developmental rate in P. xylostella. In this study we used a transient
      expression technique to micro-inject individual CpBV genome segments, and tested
      their ability to induce delayed larval development of P. xylostella. We
      demonstrated that a CpBV segment was able to express its own encoded genes when
      it was injected into nonparasitized larvae, in which the expression patterns of
      the segment genes were similar to those in the larvae parasitized by C.
      plutellae. Twenty three CpBV genome segments were individually cloned and
      injected into the second instar larvae of P. xylostella and their effects
      assessed by measuring the time taken for host development to the cocooning stage.
      Three CpBV genome segments markedly interfered with the host larval development.
      When the putative genes of these segments were analyzed, it was found that they
      did not share any common genes. Among these segments able to delay host
      development, segment S27 was predicted to encode seven protein tyrosine
      phosphatases (CpBV-PTPs), some of which were mutated by insertional inactivation
      with transposons, while other encoded gene expressions were unaffected. The
      mutant segments were unable to induce prolonged larval development of P.
      xylostella. These results suggest that CpBV can induce prolonged larval
      development of P. xylostella, and that at least some CpBV-PTPs may contribute to
      the parasitic role probably by altering titers of developmental hormones.

PMID- 20138887
TI  - Orai1 and Stim1 regulate normal and hypertrophic growth in cardiomyocytes.
AB  - Cardiac hypertrophy is an independent risk for heart failure (HF) and sudden
      death. Deciphering signalling pathways dependent on extracellular calcium
      (Ca(2+)) influx that control normal and pathological cardiac growth may enable
      identification of novel therapeutic targets. The objective of the present study
      is to determine the role of the Ca(2+) release-activated Ca(2+) (CRAC) channel
      Orai1 and stromal interaction molecule 1 (Stim1) in postnatal cardiomyocyte store
      operated Ca(2+) entry (SOCE) and impact on normal and hypertrophic postnatal
      cardiomyocyte growth. Employing a combination of siRNA-mediated gene silencing,
      cultured neonatal rat ventricular cardiomyocytes together with indirect
      immunofluorescence, epifluorescent Ca(2+) imaging and site-specific protein
      phosphorylation and real-time mRNA expression analysis, we show for the first
      time that both Orai1 and Stim1 are present in cardiomyocytes and required for
      SOCE due to intracellular Ca(2+) store depletion by thapsigargin. Stim1-KD but
      not Orai1-KD significantly decreased diastolic Ca(2+) levels and caffeine
      releasable Ca(2+) from the sarcoplasmic reticulum (SR). Conversely, Orai1-KD but
      not Stim1-KD significantly diminished basal NRCM cell size, anp and bnp mRNA
      levels and activity of the calcineurin (CnA) signalling pathway although
      diminishing both Orai1 and Stim1 proteins similarly attenuated calmodulin kinase
      II (CamKII) and ERK1/2 activity under basal conditions. Both Orai1- and Stim1-KD
      completely abrogated phenylephrine (PE) mediated hypertrophic NRCM growth and
      enhanced natriuretic factor expression by inhibiting G(q)-protein conveyed
      activation of the CamKII and ERK1/2 signalling pathway. Interestingly, only Orai1
      KD but not Stim1-KD prevented Gq-mediated CaN-dependent prohypertrophic
      signalling. This study shows for the first time that both Orai1 and Stim1 have a
      key role in cardiomyocyte SOCE regulating both normal and hypertrophic postnatal
      cardiac growth in vitro.

PMID- 20138888
TI  - Dysregulation of cadherins in the intercalated disc of the spontaneously
      hypertensive stroke-prone rat.
AB  - The structural integrity of cardiac cells is maintained by the Ca(2+)-dependent
      homophilic cell-cell adhesion of cadherins. N-cadherin is responsible for this
      adhesion under normal physiological conditions. The role of cadherins in adverse
      cardiac pathology is less clear. We studied the hearts of the stroke-prone
      spontaneously hypertensive (SHRSP) rat as a genetic model of cardiac hypertrophy
      and compared them to Wistar-Kyoto control animals. Western blotting of protein
      homogenates from 12-week old SHRSP animals indicated that similar levels of beta,
      gamma-, and alpha-catenin and T, N and R-cadherin were expressed in the control
      and SHRSP animals. However, dramatically higher levels of E-cadherin were
      detected in SHRSP animals compared to controls at 6, 12 and 18 weeks of age. This
      was confirmed by quantitative Taqman PCR and immunohistochemistry. E-cadherin was
      located at the intercalated disc of the myocytes in co-localisation with connexin
      43. Adenoviral overexpression of E-cadherin in rat H9c2 cells and primary rabbit
      myocytes resulted in a significant reduction in myocyte cell diameter and
      breadth. E-cadherin overexpression resulted in re-localisation of beta-catenin to
      the cell surface particularly to cell-cell junctions. Subsequent
      immunohistochemistry of the hearts of WKY and SHRSP animals also revealed
      increased levels of beta-catenin in the intercalated disc in the SHRSP compared
      to WKY. Therefore, remodelling of the intercalated disc in the hearts of SHRSP
      animals may contribute to the altered function observed in these animals.

PMID- 20138889
TI  - A single-domain llama antibody potently inhibits the enzymatic activity of
      botulinum neurotoxin by binding to the non-catalytic alpha-exosite binding
      region.
AB  - Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a
      severe and frequently fatal disease. Current treatments rely on antitoxins,
      which, while effective, cannot reverse symptoms once BoNT has entered the neuron.
      For treatments that can reverse intoxication, interest has focused on developing
      inhibitors of the enzymatic BoNT light chain (BoNT Lc). Such inhibitors typically
      mimic substrate and bind in or around the substrate cleavage pocket. To explore
      the full range of binding sites for serotype A light chain (BoNT/A Lc)
      inhibitors, we created a library of non-immune llama single-domain VHH (camelid
      heavy-chain variable region derived from heavy-chain-only antibody) antibodies
      displayed on the surface of the yeast Saccharomyces cerevisiae. Library selection
      on BoNT/A Lc yielded 15 yeast-displayed VHH with equilibrium dissociation
      constants (K(d)) from 230 to 0.03 nM measured by flow cytometry. Eight of 15 VHH
      inhibited the cleavage of substrate SNAP25 (synaptosome-associated protein of
      25,000 Da) by BoNT/A Lc. The most potent VHH (Aa1) had a solution K(d) for BoNT/A
      Lc of 1.47 x 10(-)(10) M and an IC(50) (50% inhibitory concentration) of 4.7 x
      10(-)(10) M and was resistant to heat denaturation and reducing conditions. To
      understand the mechanism by which Aa1 inhibited catalysis, we solved the X-ray
      crystal structure of the BoNT/A Lc-Aa1 VHH complex at 2.6 A resolution. The
      structure reveals that the Aa1 VHH binds in the alpha-exosite of the BoNT/A Lc,
      far from the active site for catalysis. The study validates the utility of non
      immune llama VHH libraries as a source of enzyme inhibitors and identifies the
      BoNT/A Lc alpha-exosite as a target for inhibitor development.

PMID- 20138890
TI  - Structural and functional analyses of beta-glucosidase 3B from Thermotoga
      neapolitana: a thermostable three-domain representative of glycoside hydrolase 3.
AB  - Based on sequence and phylogenetic analyses, glycoside hydrolase (GH) family 3
      can be divided into several clusters that differ in the length of their primary
      sequences. However, structural data on representatives of GH3 are still scarce,
      since only three of their structures are known and only one of them has been
      thoroughly characterized-that of an exohydrolase from barley. To allow a deeper
      structural understanding of the GH3 family, we have determined the crystal
      structure of the thermostable beta-glucosidase from Thermotoga neapolitana, which
      has potentially important applications in environmentally friendly industrial
      biosynthesis at a resolution of 2.05 A. Selected active-site mutants have been
      characterized kinetically, and the structure of the mutant D242A is presented at
      2.1 A resolution. Bgl3B from Th. neapolitana is the first example of a GH3
      glucosidase with a three-domain structure. It is composed of an (alpha/beta)(8)
      domain similar to a triose phosphate isomerase barrel, a five-stranded alpha/beta
      sandwich domain (both of which are important for active-site organization), and a
      C-terminal fibronectin type III domain of unknown function. Remarkably, the
      direction of the second beta-strand of the triose phosphate isomerase barrel
      domain is reversed, which has implications for the active-site shape. The active
      site, at the interface of domains 1 and 2, is much more open to solvent than the
      corresponding site in the structurally homologous enzyme from barley, and only
      the -1 site is well defined. The structures, in combination with kinetic studies
      of active-site variants, allow the identification of essential catalytic residues
      (the nucleophile D242 and the acid/base E458), as well as other residues at the 
      1 subsite, including D58 and W243, which, by mutagenesis, are shown to be
      important for substrate accommodation/interaction. The position of the
      fibronectin type III domain excludes a direct participation of this domain in the
      recognition of small substrates, although it may be involved in the anchoring of
      the enzyme on large polymeric substrates and in thermostability.

PMID- 20138891
TI  - Crystal structure and catalytic mechanism of leucoanthocyanidin reductase from
      Vitis vinifera.
AB  - Leucoanthocyanidin reductase (LAR) catalyzes the NADPH-dependent reduction of
      2R,3S,4S-flavan-3,4-diols into 2R,3S-flavan-3-ols, a subfamily of flavonoids that
      is important for plant survival and for human nutrition. LAR1 from Vitis vinifera
      has been co-crystallized with or without NADPH and one of its natural products,
      (+)-catechin. Crystals diffract to a resolution between 1.75 and 2.72 A. The
      coenzyme and substrate binding pocket is preformed in the apoprotein and not
      markedly altered upon NADPH binding. The structure of the abortive ternary
      complex, determined at a resolution of 2.28 A, indicates the ordering of a short
      3(10) helix associated with substrate binding and suggests that His122 and Lys140
      act as acid-base catalysts. Based on our 3D structures, a two-step catalytic
      mechanism is proposed, in which a concerted dehydration precedes an NADPH
      mediated hydride transfer at C4. The dehydration step involves a Lys-catalyzed
      deprotonation of the phenolic OH7 through a bridging water molecule and a His
      catalyzed protonation of the benzylic hydroxyl at C4. The resulting quinone
      methide serves as an electrophilic target for hydride transfer at C4. LAR belongs
      to the short-chain dehydrogenase/reductase superfamily and to the PIP
      (pinoresinol-lariciresinol reductase, isoflavone reductase, and phenylcoumaran
      benzylic ether reductase) family. Our data support the concept that all PIP
      enzymes reduce a quinone methide intermediate and that the major role of the only
      residue that has been conserved from the short-chain dehydrogenase/reductase
      catalytic triad (Ser...TyrXXXLys), that is, lysine, is to promote the formation
      of this intermediate by catalyzing the deprotonation of a phenolic hydroxyl. For
      some PIP enzymes, this lysine-catalyzed proton abstraction may be sufficient to
      trigger the extrusion of the leaving group, whereas in LAR, the extrusion of a
      hydroxide group requires a more sophisticated mechanism of concerted acid-base
      catalysis that involves histidine and takes advantage of the OH4, OH5, and OH7
      substituents of leucoanthocyanidins.

PMID- 20138892
TI  - A survey of lambda repressor fragments from two-state to downhill folding.
AB  - We survey the two-state to downhill folding transition by examining 20 lambda(6
      85)* mutants that cover a wide range of stabilities and folding rates. We
      investigated four new lambda(6-85)* mutants designed to fold especially rapidly.
      Two were engineered using the core remodeling of Lim and Sauer, and two were
      engineered using Ferreiro et al.'s frustratometer. These proteins have probe
      dependent melting temperatures as high as 80 degrees C and exhibit a fast
      molecular phase with the characteristic temperature dependence of the amplitude
      expected for downhill folding. The survey reveals a correlation between melting
      temperature and downhill folding previously observed for the beta-sheet protein
      WW domain. A simple model explains this correlation and predicts the melting
      temperature at which downhill folding becomes possible. An X-ray crystal
      structure with a 1.64-A resolution of a fast-folding mutant fragment shows
      regions of enhanced rigidity compared to the full wild-type protein.

PMID- 20138893
TI  - Shape and flexibility in the titin 11-domain super-repeat.
AB  - Titin is a giant protein of striated muscle with important roles in the assembly,
      intracellular signalling and passive mechanical properties of sarcomeres. The
      molecule consists principally of approximately 300 immunoglobulin and fibronectin
      domains arranged in a chain more than 1 mum long. The isoform-dependent N
      terminal part of the molecule forms an elastic connection between the end of the
      thick filament and the Z-line. The larger, constitutively expressed C-terminal
      part is bound to the thick filament. Through most of the thick filament part, the
      immunoglobulin and fibronectin domains are arranged in a repeating pattern of 11
      domains termed the 'large super-repeat'. There are 11 contiguous copies of the
      large super-repeat making up a segment of the molecule nearly 0.5 mum long. We
      have studied a set of two-domain and three-domain recombinant fragments from the
      large super-repeat region by electron microscopy, synchrotron X-ray solution
      scattering and analytical ultracentrifugation, with the goal of reconstructing
      the overall structure of this part of titin. The data illustrate different
      average conformations in different domain pairs, which correlate with differences
      in interdomain linker lengths. They also illustrate interdomain bending and
      flexibility around average conformations. Overall, the data favour a helical
      conformation in the super-repeat. They also suggest that this region of titin is
      dimerized when bound to the thick filament.

PMID- 20138895
TI  - Catabolite repression of SOS-dependent and SOS-independent spontaneous
      mutagenesis in stationary-phase Escherichia coli.
AB  - Previous work in our laboratory established that a spontaneous mutagenesis
      process operating in stationary-phase Escherichia coli cells undergoing selection
      is subject to regulation by the global regulatory mechanism known as catabolite
      repression (formerly also called glucose-repression). Here, we set out to
      determine the identity of this hitherto unknown catabolite-repressible
      spontaneous mutation generation mechanism(s). We used two different spontaneous
      mutation detection assays, reversion of a Lac(-) (lacI33OmegalacZ) frameshift
      marker and forward mutation to valine-resistance, and tested the effects of
      varying the nature of the carbon source(s) present in the selective plating
      medium on the mutability of bacterial cells carrying known defects in the recA,
      umuDC and dinB genes, three well-known SOS response genes, whose products are
      important for mutagenesis in E. coli. Consistent with the results of our previous
      Lac(-)-->Lac(+) assay using otherwise SOS-proficient bacterial cells, we found
      that the overall numbers of spontaneous Lac(+)E. coli revertants were highest
      when the selective medium contained lactose and lowest when it contained lactose
      plus the non-utilizable but strongly catabolite-repressing glucose analogue,
      methyl-alpha-d-glucopyranoside (alphaMG). In contrast, we found that the numbers
      of Lac(+) revertants appearing on the lactose and lactose+alphaMG selection
      plates were greatly diminished and not significantly different when the bacterial
      cells concerned carried either a DeltarecA or DeltadinB mutation. Furthermore,
      introducing the DeltadinB mutant allele into bacterial cells over-expressing the
      recA gene reduced the numbers of Lac(+) mutations to those being recovered with
      the DeltadinB cells. These results appear to suggest that (i) the DinB-dependent
      mutation generation pathway is alone responsible for spontaneous reversion of the
      lacI33OmegalacZ frameshift marker, and (ii) the varying numbers of Lac(+)
      colonies that we recover on the lactose and lactose+alphaMG plates provide a
      direct measure of the differential effects of these particular carbon compounds
      on the overall expression of the dinB gene. Interestingly, the yields of
      spontaneous Val mutations arising in wild-type, DeltarecA, DeltadinB and
      DeltaumuDC cells were found to be similar, but always tended to be highest when
      the medium contained only a non-repressing carbon source (glycerol) and lowest
      when it had been supplemented with a strong catabolite repressor such as glucose
      or alphaMG. Together, our results would seem to establish that stationary-phase
      E. coli cells exposed to strong selection pressures can accumulate spontaneous
      mutations via SOS-dependent and SOS-independent mutation generation pathways
      whose levels of expression are regulated by catabolite repression.

PMID- 20138894
TI  - Protein-facilitated folding of group II intron ribozymes.
AB  - Multiple studies hypothesize that DEAD-box proteins facilitate folding of the
      ai5gamma group II intron. However, these conclusions are generally inferred from
      splicing kinetics, and not from direct monitoring of DEAD-box protein-facilitated
      folding of the intron. Using native gel electrophoresis and dimethyl sulfate
      structural probing, we monitored Mss-116-facilitated folding of ai5gamma intron
      ribozymes and a catalytically active self-splicing RNA containing full-length
      intron and short exons. We found that the protein directly stimulates folding of
      these RNAs by accelerating formation of the compact near-native state. This
      process occurs in an ATP-independent manner, although ATP is required for the
      protein turnover. As Mss 116 binds RNA nonspecifically, most binding events do
      not result in the formation of the compact state, and ATP is required for the
      protein to dissociate from such nonproductive complexes and rebind the unfolded
      RNA. Results obtained from experiments at different concentrations of magnesium
      ions suggest that Mss 116 stimulates folding of ai5gamma ribozymes by promoting
      the formation of unstable folding intermediates, which is then followed by a
      cascade of folding events resulting in the formation of the compact near-native
      state. Dimethyl sulfate probing results suggest that the compact state formed in
      the presence of the protein is identical to the near-native state formed more
      slowly in its absence. Our results also indicate that Mss 116 does not stabilize
      the native state of the ribozyme, but that such stabilization results from
      binding of attached exons.

PMID- 20138896
TI  - Trait anxiety affects decision-making differently in healthy men and women:
      towards gender-specific endophenotypes of anxiety.
AB  - Excessive levels of trait anxiety are a risk factor for psychiatric conditions,
      including anxiety disorders and substance abuse. High trait anxiety has been
      associated with altered cognitive functioning, in particular with an attentional
      bias towards aversive stimuli. Decision-making is a crucial aspect of cognitive
      functioning that relies on the correct processing and control of emotional
      stimuli. Interestingly, anxiety and decision-making share underlying neural
      substrates, involving cortico-limbic pathways, including the amygdala, striatum
      and medial and dorsolateral prefrontal cortices. In the present study, we
      investigated the relationship between trait anxiety, measured by the State-Trait
      Anxiety Inventory, and complex decision-making, measured by the Iowa Gambling
      Task, in healthy male and female volunteers. The main focus of this study was the
      inclusion of gender as a discriminative factor. Indeed, we found distinct gender
      specific effects of trait anxiety: in men, both low and high anxiety groups
      showed impaired decision-making compared to medium anxiety individuals, whereas
      in women only high anxiety individuals performed poorly. Furthermore, anxiety
      affected decision-making in men early in the task, i.e. the exploration phase, as
      opposed to an effect on performance in women during the second part of the test,
      i.e. the exploitation phase. These findings were related to different profiles of
      trait anxiety in men and women, and were independent of performance in the
      Wisconsin Card Sorting Test and cortisol levels. Our data show gender-specific
      effects of trait anxiety on emotional decision-making. We suggest gender-specific
      endophenotypes of anxiety to exist, that differentially affect cognitive
      functioning.

PMID- 20138897
TI  - Effects of lateral head inclination on multimodal spatial orientation judgments
      in neglect: evidence for impaired spatial orientation constancy.
AB  - Recent research revealed that patients with spatial hemineglect show deficits in
      the judgment of the subjective vertical and horizontal. Systematic deviations in
      the subjective axes have been demonstrated in the visual and tactile modality,
      indicating a supramodal spatial orientation deficit. Further, the magnitude of
      the bias was shown to be modulated by head- and body-position. The present study
      investigated the effect of passive lateral head inclination on the subjective
      visual and tactile vertical and horizontal in neglect patients, control patients
      with left- or right-sided brain damage without neglect and healthy controls.
      Subjects performed visual- and tactile-spatial judgments of axis orientations in
      an upright head orientation and with lateral head inclination 25 degrees in
      clockwise (CW) or counterclockwise (CCW) direction. Neglect patients displayed a
      marked variability as well as a systematic tilt in their spatial judgments. In
      line with a multisensory spatial orientation deficit their subjective vertical
      and horizontal was tilted CCW in the visual and in the tactile modality, while
      such a tilt was not evident in any other subject group. Furthermore, lateral head
      inclination had a differential effect in neglect patients, but not in control
      subjects. Neglect patients' judgments were modulated in the direction of the head
      tilt ('A-effect'). That is, a CCW inclination further increased the CCW spatial
      bias whereas a CW inclination decreased the spatial bias and thus led to
      approximately normal performance. The increased A-effect might be caused by a
      pathologically strong attraction of the subjective vertical by an idiotropic
      vector relying on the actual head orientation, as a consequence of impaired
      processing of gravitational information in neglect patients.

PMID- 20138898
TI  - Semantic integration processes at different levels of syntactic hierarchy during
      sentence comprehension: an ERP study.
AB  - An event-related potential (ERP) study was conducted to investigate the temporal
      neural dynamics of semantic integration processes at different levels of
      syntactic hierarchy during Chinese sentence reading. In a hierarchical structure,
      subject noun+verb+numeral+classifier+object noun, the object noun is constrained
      by selectional restrictions of the classifier at the lower-level and of the verb
      at the higher-level and the classifier is also constrained by the verb at the
      higher-level. Semantic congruencies between verb, classifier, and noun were
      manipulated, resulting in five types of sentences: correct sentences, sentences
      with the single classifier-noun mismatch, sentences with the single verb-noun
      mismatch, sentences with the double-mismatch in classifier-noun and verb-noun,
      and sentences with the triple-mismatch in classifier-noun, verb-noun and verb
      classifier. Compared with correct sentences, all four types of mismatches
      elicited N400 effects on the noun, with the effect in the double-mismatch equal
      to the effect in the single classifier-noun mismatch but larger than the effect
      in the single verb-noun mismatch. In addition, the single verb-noun mismatch and
      the double-mismatch elicited a left-posterior positivity effect and an anterior
      negativity effect in the 550-800 ms time window on the noun, with the effects
      larger in the double-mismatch than in the single-mismatch. The classifier-noun
      mismatch also elicited the late anterior negativity effect on the noun. Although
      the triple-mismatch did not induce a significant late positivity effect on the
      noun, it did on the classifier. The pattern of the N400 effects suggests that
      semantic processes at different levels of syntactic hierarchy interact in
      integrating the incoming word into the prior sentence context with neither
      process overriding the other. The late-posterior positivity effect may reflect
      the coordination of various semantic integration processes across hierarchical
      levels during sentence comprehension.

PMID- 20138899
TI  - Lack of awareness for spatial and verbal constructive apraxia.
AB  - It is still a matter of debate whether constructive apraxia (CA) should be
      considered a form of apraxia or, rather, the motor expression of a more pervasive
      impairment in visuo-spatial processing. Constructive disorders were linked to
      visuo-spatial disorders and to deficits in appreciating spatial relations among
      component sub-parts or problems in reproducing three-dimensionality. We screened
      a large population of brain-damaged patients for CA. Only patients with
      constructive disorders and no signs of neglect and/or aphasia were selected. Five
      apractic subjects were tested with both visuo-spatial and verbal tasks requiring
      constructive abilities. The former ones were tests such as design copying, while
      the latter were experimental tasks built to transpose into the linguistic domain
      the constructive process as phrasing by arranging paper scraps into a sentence. A
      first result showed a constructive impairment in both the visuo-spatial and the
      linguistic domain; this finding challenges the idea that CA is confined to the
      visuo-spatial domain. A second result showed a systematic association between CA
      and unawareness for constructive disorders. Third, lack of awareness was always
      associated with a lesion in the right dorsolateral prefrontal cortex, a region
      deemed as involved in managing a conflict between intentions and sensory feed
      back. Anosognosia for constructive disorders and the potential role of the right
      prefrontal cortex in generating the impairment, are discussed in the light of
      current models of action control. The core of CA could be the inability to detect
      any inconsistency between intended and executed action rather than a deficit in
      reproducing spatial relationship.

PMID- 20138900
TI  - Reading about the actions of others: biological motion imagery and action
      congruency influence brain activity.
AB  - Prior neuroimaging research has implicated regions within and near the posterior
      superior temporal sulcus (pSTS) in the visual processing of biological motion and
      of the intentions implied by specific movements. However, it is unknown whether
      this region is engaged during the processing of human motion at a conceptual
      level, such as during story comprehension. Here, we obtained functional magnetic
      resonance images from subjects reading brief stories that described a human
      character's background and then concluded with an action or decision made by the
      character. Half of the stories contained incidental descriptions of biological
      motion (such as the character's walking or grasping) while the remaining half did
      not. As a second factor, the final action of the story was either congruent or
      incongruent with the character's background and implied goals and intentions.
      Stories that contained biological motion strongly activated the pSTS bilaterally,
      along with ventral temporal areas, premotor cortex, left motor cortex, and the
      precuneus. Active regions of pSTS in individual subjects closely overlapped with
      regions identified with a separate biological motion localizer (point-light
      display) task. Reading incongruent versus congruent stories activated dorsal
      anterior cingulate cortex and bilateral anterior insula. These results support
      the hypothesis that reading can engage higher visual cortex in a content-specific
      manner, and suggest that the presence of biological motion should be controlled
      as a potential confound in fMRI studies using story comprehension tasks.

PMID- 20138901
TI  - Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic
      evidence.
AB  - In recent decades, temporal patterns in SSB intake have shown a close parallel
      between the upsurge in obesity and rising levels of SSB consumption. SSBs are
      beverages that contain added caloric sweeteners such as sucrose, high-fructose
      corn syrup or fruit-juice concentrates, all of which result in similar metabolic
      effects. They include the full spectrum of soft drinks, carbonated soft drinks,
      fruitades, fruit drinks, sports drinks, energy and vitamin water drinks,
      sweetened iced tea, cordial, squashes, and lemonade, which collectively are the
      largest contributor to added sugar intake in the US. It has long been suspected
      that SSBs have an etiologic role in the obesity epidemic, however only recently
      have large epidemiological studies been able to quantify the relationship between
      SSB consumption and long-term weight gain, type 2 diabetes (T2DM) and
      cardiovascular disease (CVD) risk. Experimental studies have provided important
      insight into potential underlying biological mechanisms. It is thought that SSBs
      contribute to weight gain in part by incomplete compensation for energy at
      subsequent meals following intake of liquid calories. They may also increase risk
      of T2DM and CVD as a contributor to a high dietary glycemic load leading to
      inflammation, insulin resistance and impaired beta-cell function. Additional
      metabolic effects from the fructose fraction of these beverages may also promote
      accumulation of visceral adiposity, and increased hepatic de novo lipogenesis,
      and hypertension due to hyperuricemia. Consumption of SSBs should therefore be
      replaced by healthy alternatives such as water, to reduce risk of obesity and
      chronic diseases.

PMID- 20138902
TI  - Comparison of C57BL/6 and DBA/2 mice in food motivation and satiety.
AB  - Demand functions describe the relationship between the consumption of a commodity
      and its mean or unit price. In the first experiment, we analyzed food demand in
      two strains of mice (C57BL/6 and DBA/2) that differ on several behavioral
      dimensions, but have not been examined extensively for differences in feeding and
      meal patterns. Mice worked for food pellets in a continuous access closed economy
      in which total intake and meal patterns could be measured. A series of fixed
      (FUP), variable (VUP), and progressive (PUP) unit price schedules were imposed.
      Under all schedules, DBA/2 mice consumed significantly more food than C57BL/6, a
      difference that was not attributable to disparity in body weight or weight gain.
      The higher intake of DBA/2 mice was due predominantly to larger meal size
      compared with C57BL/6, with no strain difference in meal frequency. In a second
      experiment, strain differences in meal size were not found to correlate with
      anorectic sensitivity to cholecystokinin (CCK) administration, or with c-Fos
      expression induced by CCK in PVN, AP and NTS. Thus, DBA/2 mice were motivated to
      sustain a higher daily food intake and meal size than C57BL/6 under the range of
      demand costs employed in the present work, but this strain difference is unlikely
      to be due to CCK action or responsiveness.

PMID- 20138903
TI  - The influence of beverage composition on delivery of phenolic compounds from
      coffee and tea.
AB  - Epidemiological data suggest that consumption of coffee and tea is associated
      with a reduced risk of several chronic and degenerative diseases including
      cardiovascular disorders, diabetes, obesity and neurodegenerative disorders. Both
      coffee and tea are a rich source of phenolic compounds including chlorogenic
      acids in coffee; and flavan-3-ols as well as complex theaflavins and thearubigens
      in tea. Coffee and tea are two of the most commonly consumed beverages in the
      world and thus represent a significant opportunity to positively affect disease
      risk and outcomes globally. Central to this opportunity is a need to better
      understand factors that may affect the bioavailability of specific phenolic
      components from coffee and tea based beverages. An overview of the phenolic
      composition of coffee and tea is discussed in the context of how processing and
      composition might influence phenolic profiles and bioavailability of individual
      phenolic components. Specifically, the impact of beverage formulation, the extent
      and type of processing and the influence of digestion on stability,
      bioavailability and metabolism of bioactive phenolics from tea and coffee are
      discussed. The impact of co-formulation with ascorbic acid and other
      phytochemicals are discussed as strategies to improve absorption of these health
      promoting phytochemicals. A better understanding of how the beverage composition
      impacts phenolic profiles and their bioavailability is critical to development of
      beverage products designed to deliver specific health benefits.

PMID- 20138904
TI  - WAY100635 blocks the hypophagia induced by 8-OH-DPAT in the hypothalamic nuclei.
AB  - This study examined the influence of pretreatment with N-[2-[4-(2-methoxyphenyl)
      1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide maleate (WAY100635,
      full 5-HT1A receptor antagonist, 37 nmol) on feeding effects evoked by local
      injections of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, 5-HT(1A) and 5
      HT(7) receptor agonist, 6 nmol) into the LH and into the ARC of female rats
      adapted to a wet mash diet (enriched with 10% sucrose), during diestrus or
      estrus. The results showed that the LH-pretreatment with WAY100635 suppressed the
      hypophagic effects evoked by 8-OH-DPAT during estrus as well as diestrus. The ARC
      pretreatment with WAY100635 blockaded the hypophagia evoked by 8-OH-DPAT in
      estrus rats. The previous treatment with WAY100635 in the ARC also suppressed the
      feeding duration decrease evoked by 8-OH-DPAT in estrus. The latency to start
      feeding, the drinking behavior and the durations of other non-ingestive behaviors
      were not affected by the different treatments, hypothalamic regions (LH or ARC),
      and/or estrous cycle stages (diestrus and estrus), except for the locomotion
      duration increase after 8-OH-DAPT in LH-pretreated rats in diestrus. The present
      findings confirm our previous suggestion that ARC- and the LH-5-HT(1A) receptors
      participate in the serotonergic control of feeding and that these feeding-related
      serotonergic circuits in LH are affected by ovarian hormones, since the treatment
      with WAY100635 evoked a hypophagia response during the diestrus phases.

PMID- 20138905
TI  - Comparison of toluene-induced locomotor activity in four mouse strains.
AB  - The mechanisms by which abused inhalants exert their neurobehavioral effects are
      only partially understood. In research with other drugs of abuse, specific inbred
      mouse strains have been useful in exploring genetic loci important to variation
      in behavioral reactions to these drugs. In the present investigation, mice from
      three inbred strains (Balb/cByj, C57BL/6J and DBA/2J) and one outbred strain
      (Swiss Webster) were studied for their acute and chronic sensitivity to toluene
      induced changes in locomotor activity. Mice were exposed to toluene (0, 100,
      2000, 8000, and 10,000 ppm) for 30 min in static exposure chambers equipped with
      activity monitors. In the acute condition, concentrations of toluene <8000 ppm
      increased ambulatory distance while the concentrations of > or =8000 ppm induced
      temporally biphasic effects with initial increases in activity followed by
      hypoactivity. Between-group differences in absolute locomotor activity levels
      were evident. The inbred Balb/cByj and DBA/2J strains as well as the outbred
      Swiss Webster strain of mice showed greater increases in activity after an acute
      challenge exposure to 2000 ppm than the inbred C57BL/6J strain. The same animals
      were then exposed 30 min/day to 8000 ppm toluene for 14 consecutive days. Re
      determination of responses to 2000-ppm challenge exposures revealed that
      sensitization developed in locomotor activity and that the DBA/2J strain showed
      the greatest increase in sensitivity. These baseline differences in acute
      sensitivity and the differential shifts in sensitivity after repeated exposures
      among the inbred mouse strains suggest a genetic basis for the behavioral effects
      to toluene. The results support the notion that like for other drugs of abuse,
      using various strains of mice may be useful for investigating mechanisms that
      underlie risk for inhalant abuse.

PMID- 20138906
TI  - Pentylenetetrazol produces a state-dependent conditioned place aversion to
      alcohol withdrawal in mice.
AB  - The purpose of this study was to determine if aversive effects of alcohol
      withdrawal could be detected in mice using the place conditioning procedure and
      whether the GABA(A) receptor antagonist, pentylenetetrazol (PTZ), would increase
      the aversive effects of alcohol withdrawal and increase the probability of
      detecting conditioned place aversion. Subjects were alcohol-naive mice from a
      specific line selectively bred for low alcohol preference (LAP1; n=91) and were
      assigned to three groups: alcohol withdrawal, PTZ alone, and PTZ+alcohol
      withdrawal. On four trials, mice received either a 4.0 g/kg intraperitoneal
      (i.p.) injection of alcohol (alcohol withdrawal, PTZ+alcohol withdrawal groups)
      or saline (PTZ group) 8 h prior to being placed on a distinctive floor texture
      for a 30-min conditioning session. Five minutes before these sessions, mice in
      the PTZ and PTZ+alcohol withdrawal groups received PTZ (5.0 mg/kg; i.p.) and the
      alcohol withdrawal group received saline. On intervening days mice received two
      saline injections at the same time points prior to being placed on a different
      floor texture. Post-conditioning floor preference was assessed in two 60-min
      tests; the first test was drug-free and the second test was state-dependent.
      Neither alcohol withdrawal nor PTZ produced significant place conditioning. The
      PTZ+alcohol withdrawal group showed a significant place aversion during the state
      dependent test. These data suggest that the combined stimulus properties of PTZ
      and alcohol withdrawal facilitated the expression of conditioned place aversion
      to alcohol withdrawal.

PMID- 20138907
TI  - Lipase immobilization on Polysulfone globules and their performances in olive oil
      hydrolysis.
AB  - We prepared Polysulfone (PS) globules by pouring the PS solution droplets in to
      the non-solvent water. PS solutions (10, 15, and 20% (w/v), concentrations) of
      different viscosities resulted different physical appearances in globules. The
      lipase immobilizing amount (4.32 mg/g) was maximum for PS 20% globules as it
      possessed maximum BET pore surface area. The olive oil hydrolytic reaction
      parameters were fitted into the Lineweaver-Burk plot. The K(m) (apparent) values
      of all the immobilized globules were higher (83.3mM) with respect to free lipases
      (62.5mM) where as V(max) (apparent) values followed the reverse trend (129.8 U/mg
      for 20% and 120.5 U/mg for both 15% and 10% PS immobilized globules and 153.8
      U/mg for the free lipase respectively). The hydrolytic activity to olive oil was
      decreased ( approximately 16-20%) after five cycles.

PMID- 20138908
TI  - Expression of feruloyl esterase from Aspergillus awamori in Escherichia coli:
      Characterization and crystal studies of the recombinant enzyme.
AB  - This paper describes cloning, expression, characterization and crystallization of
      feruloyl esterase from Aspergillus awamori. The gene coding for feruloyl esterase
      from A. awamori was amplified, cloned, and expressed in Escherichia coli. The
      recombinant enzyme was purified, characterized and used for crystallization. Its
      X-ray crystallographic data were collected and explained using molecular
      replacement theory. Also, the tertiary structure of the recombinant enzyme
      ferulic acid complex was also determined.

PMID- 20138909
TI  - Thermodynamic basis of the thermostability of CYP175A1 from Thermus thermophilus.
AB  - Detailed circular dichroism studies have been carried out to monitor thermal as
      well as denaturant induced unfolding of CYP175A1 from Thermus thermophilus and
      its mesophilic homologue, CYP101 from Pseudomonas putida. The unfolding midpoint
      temperatures for tertiary and secondary structures of the substrate-free CYP175A1
      were found to be 83.7 degrees C and 87 degrees C respectively, while the
      corresponding midpoint temperatures for substrate-free CYP101 were at 47.7
      degrees C and 51 degrees C respectively. The apparent C(m) value for GdnHCl
      induced unfolding of secondary structure of CYP175A1 was found to be 2.6M. The
      thermodynamic stability curves determined from GdnHCl induced unfolding of the
      enzymes at different temperatures, showed that CYP175A1 had higher free energy
      compared to CYP101 at temperature >10 degrees C. The results clearly established
      that the high thermostability of CYP175A1 arises predominantly due to higher
      enthalpy of the thermostable enzyme compared to CYP101. The larger number of salt
      bridges was proposed to be responsible for higher enthalpy of stabilization of
      CYP175A1.

PMID- 20138910
TI  - Remembering perceptual features unequally bound in object and episodic tokens:
      Neural mechanisms and their electrophysiological correlates.
AB  - We present a neurocognitive model of long-term object memory. We propose that
      perceptual priming and episodic recognition are phenomena based on three distinct
      kinds of representations. We label these representations types and tokens. Types
      are prototypical representations needed for object identification. The network of
      non-arbitrary features necessary for object categorization is sharpened in the
      course of repeated identification, an effect that we call type trace and which
      causes perceptual priming. Tokens, on the other hand, support episodic
      recognition. Perirhinal structures are proposed to bind intrinsic within-object
      features into an object token that can be thought of as a consolidated perceptual
      object file. Hippocampal structures integrate object- with contextual information
      in an episodic token. The reinstatement of an object token is assumed to generate
      a feeling of familiarity, whereas recollection occurs when the reinstatement of
      an episodic token occurs. Retrieval mode and retrieval orientation dynamically
      modulate access to these representations. In this review, we apply the model to
      recent empirical research (behavioral, fMRI, and ERP data) including a series of
      studies from our own lab. We put specific emphasis on the effects that sensory
      features and their study-test match have on familiarity. The type-token approach
      fits the data and additionally provides a framework for the analysis of concepts
      like unitization and associative reinstatement.

PMID- 20138911
TI  - Anorexia nervosa and estrogen: current status of the hypothesis.
AB  - Anorexia nervosa occurs predominantly in young women. Also, recent data suggest
      that a heritable, genetic defect may contribute to this feeding disorder. These
      observations support the hypothesis that an inherited, abnormal response of the
      brain to rising levels of estrogens at puberty may contribute to the symptoms of
      weight loss in anorexia. To evaluate the merits of this hypothesis, the current
      literature on feeding depression by estrogens in anorexic patients and possible
      genetic or developmental mechanisms that could alter brain responsiveness to
      estrogens are reviewed. It is concluded that a number of specific biochemical or
      developmental pathways-abnormalities in the classical or membrane-bound forms of
      estrogen receptors, in co-activators for estrogen, in thyroxine receptors, in
      steroid metabolizing enzymes, in quantitative trait loci, in perinatal
      androgenization, and in processes of puberty-could converge to produce an
      abnormal response to estrogen and the onset of anorexia nervosa.

PMID- 20138912
TI  - The functions of steryl glycosides come to those who wait: Recent advances in
      plants, fungi, bacteria and animals.
AB  - The attachment of a sugar moiety to the 3-hydroxy group of a sterol drastically
      increases the size of the hydrophilic part of the lipid. It is obvious that the
      glycosylation of a considerable fraction of membrane-bound free sterols alters
      the biophysical properties of the membrane. However, the consequences of such
      changes in the proportions of free sterols and steryl glycosides on the
      biological functions of a membrane are still unclear. This is the main hurdle in
      understanding the biological functions of steryl glycosides on a molecular level.
      The recent cloning of sterol glycosyltransferase genes from plants, fungi and
      bacteria has enabled genetic approaches to analyze steryl glycoside functions.
      Down regulation of phytosteryl beta-glycoside biosynthesis in Arabidopsis
      thaliana causes several dysfunctions in seed development. Ergosteryl beta
      glycoside depleted mutants of the yeast Pichia pastoris lose their ability to
      degrade their peroxisomes by an autophagic mechanism called micropexophagy. In
      the plant-pathogenic fungus Colletotrichum orbiculare the same defect impairs
      invasion of the cucumber host plants. Helicobacter pylori, a bacterium colonizing
      the human stomach, is unable to modulate the host's immune response when the
      cholesteryl alpha-glycoside biosynthesis of the bacterium is mutated. These
      mutants with manipulated steryl glycoside metabolism will inspire further studies
      with cell biological, biophysical and other methods that will provide us with a
      mechanistic understanding of steryl glycoside functions.

PMID- 20138913
TI  - Video-Tracking-Box linked to Smart software as a tool for evaluation of locomotor
      activity and orientation in brain-injured rats.
AB  - Injuries of the Central Nervous System (CNS) cause devastating and irreversible
      losses of function. In order to analyze the deficits subsequent to brain injury
      it is necessary to use behavioral tests which evaluate cerebral dysfunction. In
      this study, we describe a new tool, the Video-Tracking-Box (VTB) linked to Smart
      software. This new method adequately quantifies parameters related to locomotor
      activity and orientation in brain-injured rats. This method has been used in our
      laboratory in order to measure behavioral outcome after brain injury caused by
      intracerebral hemorrhage (ICH) in adult Wistar rats. In our experimental model,
      ICH was induced by stereotactic injection of 0.5U of collagenase type IV in
      striatum. ICH injured rats decreased its motor coordination and presented
      deficits in cognitive memory. VTB-Smart test was sensitive to chronic locomotor
      and orientation dysfunction, and it was performed between 1 and 5 months after
      ICH. Our results revealed a significant increase in motor latency and loss of
      spatial orientation in the damaged-animals compared with intact animals. The data
      demonstrate that our VTB, joined to Smart software, offers a reliable measure to
      assess motor dysfunction and orientation after brain injury.

PMID- 20138914
TI  - The precision of video and photocell tracking systems and the elimination of
      tracking errors with infrared backlighting.
AB  - Automated tracking offers a number of advantages over both manual and photocell
      tracking methodologies, including increased reliability, validity, and
      flexibility of application. Despite the advantages that video offers, our
      experience has been that video systems cannot track a mouse consistently when its
      coat color is in low contrast with the background. Furthermore, the local lab
      lighting can influence how well results are quantified. To test the effect of
      lighting, we built devices that provide a known path length for any given trial
      duration, at a velocity close to the average speed of a mouse in the open-field
      and the circular water maze. We found that the validity of results from two
      commercial video tracking systems (ANY-maze and EthoVision XT) depends greatly on
      the level of contrast and the quality of the lighting. A photocell detection
      system was immune to lighting problems but yielded a path length that deviated
      from the true length. Excellent precision was achieved consistently, however,
      with video tracking using infrared backlighting in both the open field and water
      maze. A high correlation (r=0.98) between the two software systems was observed
      when infrared backlighting was used with live mice.

PMID- 20138915
TI  - Direct detection of human herpesvirus 6 DNA in serum by variant specific loop
      mediated isothermal amplification in hematopoietic stem cell transplant
      recipients.
AB  - A variant specific direct loop-mediated isothermal amplification (LAMP) method
      was developed to detect human herpesvirus-6 (HHV-6) variants in serum samples.
      Specific primers were designed against HHV-6 U86 gene. Initial validation
      analysis confirmed high specificity and sensitivity of the method. This method
      was shown to be highly reliable for monitoring active HHV-6 infection in
      hematopoietic stem cell transplant recipients.

PMID- 20138916
TI  - LUX real-time PCR assay for the detection of porcine circovirus type 2.
AB  - Light Upon eXtension real-time PCR (LUX real-time PCR) assay was developed for
      the detection of porcine circovirus type 2 (PCV2). The primers flanking a 114 bp
      fragment were selected from ORF1. The optimized assay could detect 20 viral
      copies of pBluescript SK+ plasmid containing inserted PCV2 DNA. The dynamic range
      of quantitative analysis covered a 7-order interval ranging from 20 to 2 x 10(8)
      genome equivalents per assay with the best results in the range from 2 x 10(2) to
      2 x 10(7) viral copies. The LUX real-time PCR assay had a high specificity since
      it detected PCV2 but not PCV1, CSFV, PRRSV or negative samples. There was good
      agreement between the LUX real-time PCR and the conventional PCR when lymph nodes
      from PCV2 infected animals were tested. A comparison of the LUX real-time PCR
      with the TaqMan PCR and SYBR Green PCR indicated that the amount of viral copies
      determined using linear calibration curve differed from assay to assay but not
      more than an order. LUX real-time PCR, similar to the TaqMan PCR, was more
      specific for generation of fluorogenic signal than SYBR Green PCR.

PMID- 20138917
TI  - Evaluation of novel H1N1-specific primer-probe sets using commercial RT-PCR
      mixtures and a premixed reaction stored in a lyophilized format.
AB  - The recent emergence of a novel H1N1 influenza A virus in humans caused the first
      influenza pandemic of this century. Many clinical diagnostic laboratories are
      overwhelmed by the testing demands related to the infection. Three novel H1N1
      specific primer-probe sets reported during the early phase of the pandemic were
      tested in three commercial real-time RT-PCR mixtures. The amplification
      efficiencies and detection limits of these assays were determined. A ready-to-use
      premixed RT-PCR stored in a lyophilized format was developed. The detection
      limits of the studied assays were highly variable, ranging from 1.68E-01 to 1.68E
      05 TCID(50) per reaction. The detection limit of the lyophilized reaction mixture
      was found to be 1.68E-05 TCID(50) per reaction, but the amplification efficiency
      of the assay was lower than those deduced from the other assays. All respiratory
      samples from infected patients and all control nasopharyngeal aspirates were
      positive and negative, respectively, in the newly developed assay. The results
      highlighted that, to enhance the sensitivity of an assay, it is essential to
      evaluate a primer-probe set with different commercial RT-PCR assays. This study
      also demonstrated the feasibility of using lyophilized reaction mixtures for the
      molecular diagnosis of novel H1N1.

PMID- 20138918
TI  - Susceptibility of a potential animal model for pathological anxiety to chronic
      mild stress.
AB  - When anxiety-related behaviour in animals appears to lack adaptive value, it
      might be defined as pathological. Adaptive behaviour can be assessed for example
      by changes in behavioural responses over time, i.e. habituation. Thus, non
      adaptive anxiety would be reflected by a lack of habituation. Recently, we found
      that 129P3/J mice are characterised by non-adaptive avoidance behaviour after
      repeated test exposure. The present study was aimed at investigating the
      sensitivity of the behavioural profile of these animals to exposure to a chronic
      mild stress (CMS) paradigm followed by repeated exposure to the modified hole
      board test. If the behavioural profile of 129P3/J mice mirrors pathological
      anxiety, their behavioural habituation under repeated test exposure conditions
      should be affected by CMS treatment. The results confirm the profound lack of
      habituation with respect to anxiety-related behaviour in both control and CMS
      treated mice. Additionally, CMS treated animals revealed a lower exploratory
      behaviour, reduced locomotor activity and increased arousal-related behaviour
      over time when compared to control individuals, proving an extension of their
      impaired habituation behaviour. Although no effects of CMS treatment on plasma
      corticosterone levels were found, higher immediate early gene expression in the
      bed nucleus of the stria terminalis and the ventrolateral periaqueductal grey in
      CMS treated mice indicated that 129P3/J mice are susceptible to the negative
      effects of CMS treatment at both the behavioural and the functional level. These
      results support the hypothesis that 129P3/J mice might be an interesting model
      for pathological anxiety.

PMID- 20138919
TI  - Effect of deep brain stimulation in the pedunculopontine nucleus on motor
      function in the rat 6-hydroxydopamine Parkinson model.
AB  - The pedunculopontine nucleus (PPN) has been introduced only recently as a new
      target for deep brain stimulation (DBS) to treat gait disorders and postural
      instability in Parkinson's disease (PD). We here tested whether the 6
      hydroxydopamine (6-OHDA) PD rat model can be used to study the pathophysiological
      mechanisms of DBS of the pedunculopontine tegmental nucleus (PPTg), the
      equivalent to the human PPN. In male Sprague-Dawley rats with unilateral 6-OHDA
      induced nigrostriatal lesions and an electrode implanted into the ipsilateral
      PPTg the individual threshold for stimulation-induced side effects was higher for
      25 than for 130Hz, and lower for lesioned compared to sham-lesioned controls.
      Rats were thus divided into four groups, (1) sham-stimulation, (2,3) 130Hz and
      25Hz stimulation with the individual threshold determined for 130Hz, and (4) 25Hz
      stimulation at 20% below threshold (25Hz high). After 24h stimulation the rats
      were tested for limb use contralateral to the lesion (cylinder test and adhesive
      removal test), for locomotor activity (open field), and for postural instability
      (pole test). In lesioned rats 130Hz and 25Hz high stimulation improved postural
      instability in the pole test, but deteriorated limb use during adhesive removal.
      Additionally, 25Hz high deteriorated motor activity in the cylinder test and open
      field, while 25Hz stimulation marginally improved activity. Sham-lesioned rats
      were not affected by stimulation. Stimulation with different frequencies and
      intensities had complex effects on behavioral function tested. The present data
      provide foundation for future investigations on DBS of the PPTg in sensorimotor
      functions.

PMID- 20138920
TI  - Vitamin E improves learning performance and changes the expression of nitric
      oxide-producing neurons in the brains of diabetic rats.
AB  - We investigated the effects of chronic administration of vitamin E on nitric
      oxide (NO)-producing neurons in the brains of streptozotocin (STZ)-induced
      diabetic rats using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH
      d) histochemistry. We further evaluated the effects of diabetes and vitamin E
      treatment on experimental anxiety and memory processes using the elevated plus
      maze (EPM) Trial 1/2 protocol. Wistar rats were divided into four groups:
      normoglycemics (N), normoglycemics treated with vitamin E (NVE), diabetics (D),
      and diabetics treated with vitamin E (DVE). Diabetes mellitus was induced by a
      single intraperitoneal injection of STZ (35mg/kg). Vitamin E (100mg/kg) or
      vehicle was administered orally by gavage (1ml/kg) once each day for 7 weeks.
      After behavioral testing, the dentate gyrus of the hippocampus (DG), striatum,
      paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON), and
      dorsolateral periaqueductal grey (DLPAG) were analyzed for NADPH-d
      histochemistry. STZ-induced diabetic rats exhibited decreased locomotor activity
      and cognitive impairment compared with normoglycemic controls. The number of
      NADPH-d-positive neurons was increased in the DG, striatum, and DLPAG of diabetic
      rats. An increase in soma area was detected in all structures analyzed (DG,
      striatum, PVN, SON, and DLPAG) of STZ-induced diabetic animals. The present study
      showed that chronic administration of vitamin E ameliorates memory in STZ-induced
      diabetic rats and revealed that NOS-producing neurons have an increased soma area
      which can be restored, at least partially, by vitamin E treatment. These results
      suggest the potential use of vitamin E as an adjuvant therapy for the prevention
      and treatment of diabetic conditions.

PMID- 20138921
TI  - Lack of involvement of alpha-synuclein in unconditioned anxiety in mice.
AB  - Alpha-synuclein is implicated in the pathology of Parkinson disease (PD) and is
      involved in synaptic function, particularly in presynaptic events in dopamine
      (DA) synapses. Recently, a role for alpha-synuclein in reward and addiction,
      especially in alcoholism, has been reported. Since PD and alcohol dependence
      present a strong comorbidity with anxiety disorders, a role for alpha-synuclein
      in anxiety has been proposed. The aim of the present investigation was to study
      the involvement of alpha-synuclein in anxiety by testing alpha-synuclein knock
      out and wild type mice in three different emotionality tests: the open field, the
      elevated plus maze and the light-dark box. Alpha-synuclein knock out mice and
      wild type controls displayed consistently similar emotionality profiles in all
      the tests, suggesting a lack of involvement of alpha-synuclein in unconditioned
      anxiety in mice.

PMID- 20138922
TI  - The periaqueductal gray and its potential role in maternal behavior inhibition in
      response to predatory threats.
AB  - Animals faced with conflicting cues, such as predatory threat and a given
      rewarding stimulus, must make rapid decisions to engage in defensive versus other
      appetitive behaviors. The brain mechanisms mediating such responses are poorly
      understood. However, the periaqueductal gray (PAG) seems particularly suitable
      for accomplishing this task. The PAG is thought to have, at least, two distinct
      general roles on the organization of motivated responses, i.e., one on the
      execution of defensive and reproductive behaviors, and the other on the
      motivational drive underlying adaptive responses. We have presently examined how
      the PAG would be involved in mediating the behavioral choice between mutually
      incompatible behaviors, such as reproduction or defense, when dams are exposed to
      pups and cat odor. First, we established the behavioral protocol and observed
      that lactating rats, simultaneously exposed to pups and cat odor, inhibited
      maternal behavior and expressed clear defensive responses. We have further
      revealed that cat odor exposure up-regulated Fos expression in the dorsal PAG,
      and that NMDA cytotoxic lesions therein were able to restore maternal responses,
      and, at the same time, block defensive responsiveness to cat odor. Potential
      paths mediating the dorsal PAG influences on the inhibition of appetitive (i.e.,
      retrieving behavior) and consummatory (i.e., nursing) maternal responses are
      discussed. Overall, we were able to confirm the dual role of the PAG, where, in
      the present case, the dorsal PAG, apart from organizing defensive responses, also
      appears to account for the behavioral inhibition of non-defensive responses.

PMID- 20138923
TI  - The effects of strain and prenatal nicotine exposure on ethanol consumption by
      adolescent male and female rats.
AB  - Two studies of variables affecting voluntary ethanol consumption by adolescent
      male and female rats are reported. Sprague-Dawley (SD) and spontaneously
      hypertensive rats (SHRs) were compared in Experiment 1. Starting on postnatal day
      30 all had 24-h access to 2%, then 4%, and then 6% ethanol, followed by 1-h
      access to the 6% until intake stabilized. During the 1-h access SHR females
      consumed more ethanol than all other groups. In Experiment 2, the same procedure
      was used to compare SD groups prenatally exposed to nicotine, with controls.
      Nicotine-exposed females consumed more ethanol during 1-h access than both
      nicotine-exposed and control males; but after using water intake as a covariate,
      the differences were not significant. These data show that deprivation conditions
      need to be considered when generalizing the results of voluntary consumption
      studies, and that estrogens may be a modulator of addictive behavior.

PMID- 20138924
TI  - The protease resistant surface (PRS) glycoconjugate from Trypanosoma congolense
      has an inositol-acylated glycosylphosphatidylinositol anchor, containing a
      significant proportion of myristate at the sn-2 position.
AB  - In the tsetse fly, the surface of Trypanosoma congolense parasites is covered by
      a dense layer of glycosylphosphatidylinositol (GPI)-anchored molecules. These
      include EPGENGT procyclin and protease resistant surface molecule (PRS), as well
      as congolense epimastigote-specific protein, CESP, and glutamic acid- and alanine
      rich protein (GARP). The GPI structures of EPGENGT and GARP have been partially
      elucidated, but very little is known about PRS. We now purified PRS and analyzed
      its GPI lipid structure and carbohydrate composition using mass spectrometry. We
      found that unlike EPGENGT and GARP, the GPI anchor of PRS is unusually composed
      of inositol-acylated diacyl-phosphatidylinositols, including species containing
      either myristic or oleic acid at the sn-2 position of the glycerol backbone. This
      is the first identification of a tri-acylated GPI anchor containing myristate in
      procyclic form trypanosomes. In addition, we found that PRS is highly rich in
      galactose and sialic acid residues, suggesting that it may represent a major
      acceptor of the parasite trans-sialidase.

PMID- 20138925
TI  - Monitoring of phytoplankton community structure using terminal restriction
      fragment length polymorphism (T-RFLP).
AB  - To establish molecular monitoring for the phytoplankton community in aquatic
      ecosystems, we analysed the terminal restriction fragment length polymorphism (T
      RFLP) of small subunit ribosomal RNA gene (18S rDNA) sequences of nuclear genomes
      from the algal strains of culture collections and environmental samples of two
      freshwater reservoirs (Sangcheon reservoir and Seoho reservoir, Korea). Terminal
      restriction fragment (T-RF) length database was also constructed from twelve
      strains of algal culture collections to annotate and identify the phytoplankton
      species from T-RFLP profiles. Algal species in reservoirs were identified and
      monitored through the colony sequencing and T-RF length patterns of 18S rRNA. In
      this study, 41 unique clones were identified from two reservoirs including
      Chlorophyta, Cryptophyta, and Alveolata. In the case of Cryptomonas sp., we found
      significant linear relationships between T-RF peak areas and biovolumes by cell
      counting. Our results suggest that T-RFLP analysis can be a fast and quantitative
      monitoring tool for species changes in phytoplankton communities.

PMID- 20138926
TI  - Carbachol injection into the pontine reticular formation depresses laryngeal
      muscle activities and airway reflexes in decerebrate cats.
AB  - To understand the role of cholinoceptive, medial pontine reticular formation
      (mPRF) neurons in the control of upper airway, pharyngolaryngeal reflexes, we
      measured activities of intrinsic laryngeal muscles (posterior cricoarytenoid,
      PCA; thyroarytenoid, TA), diaphragm (DIA), genioglossus (GG) and a neck muscle
      (trapezius) in unanesthetized, decerebrated, spontaneously breathing cats with
      and without mPRF carbachol injections. The ethimoidal nerve was electrically
      stimulated to evoke sneezing, and the superior laryngeal nerve to evoke the
      laryngeal reflex, swallowing, and coughing. Carbachol reduced the amplitudes of
      the spontaneous electromyographic activities in the neck, TA, PCA, GG, and DIA to
      7%, 30%, 54%, 45% and 71% of control, respectively, reduced the respiratory rate
      to 53% without changes in expiratory CO(2) concentration; the magnitude of the
      laryngeal reflex in the TA muscle to 56%; increased its latency by 13%; and
      reduced the probability of stimulus-induced sneezing, swallowing, and coughing to
      less than 40%. These changes lasted more than 1h. These data demonstrate that
      important upper airway reflexes are suppressed by increasing cholinergic
      neurotransmission in the mPRF. Because acetylcholine release in the mPRF changes
      in accordance with sleep-wake cycles, the present findings are relevant to the
      control of upper airway reflexes during various vigilance states.

PMID- 20138927
TI  - Improved hydrogen production with expression of hemH and lba genes in chloroplast
      of Chlamydomonas reinhardtii.
AB  - The coding region of both the ferrochelatase gene, hemH, from Bradyrhizobium
      japonicum, and the leghemoglobin gene, lba, from Glycine max, were transferred
      into chloroplast of Chlamydomonas reinhardtii. As a result, transgenic C.
      reinhardtii cultures more rapidly consumed O(2) and increased H(2) output
      compared with controls in both sulfur-free and sulfur-containing medium. H(2)
      production of the transgenic algal cultures in sulfur-free medium was 4-fold
      greater than that of control cultures, approximately 3.3mlbottle(-1). Maximum
      expression of the hemH-lba fusion protein on day 5 coincided with the lowest
      levels of O(2) content and the highest H(2) evolution rate detected over 7 days
      of anaerobic induction in sulfur-free medium. When the concentration of sulfate
      in the growth medium was restored to 12.5 or 50microM, O(2) consumption and H(2)
      yield decreased more slowly in the transgenic algal cultures than in the control
      cultures. These results demonstrate that expression of the hemH-lba fusion
      protein in chloroplast of C. reinhardtii improved their H(2) yield by decreasing
      O(2) content in the medium, thereby representing the potential for H(2)
      production in green algae to be improved.

PMID- 20138928
TI  - Marker-free plasmids for gene therapeutic applications--lack of antibiotic
      resistance gene substantially improves the manufacturing process.
AB  - Plasmid DNA is being considered as a promising alternative to traditional protein
      vaccines or viral delivery methods for gene therapeutic applications. DNA-based
      products are highly flexible, stable, are easily stored and can be manufactured
      on a large scale. Although, much safer than viral approaches, issues have been
      raised with regard to safety due to possible integration of plasmid DNA into
      cellular DNA or spread of antibiotic resistance genes to intestinal bacteria by
      horizontal gene transfer. Accordingly, there is interest in methods for the
      production of plasmid DNA that lacks the antibiotic resistance gene to further
      improve their safety profile. Here, we report for the first time the gram-scale
      manufacturing of a minimized plasmid that is devoid of any additional sequence
      elements on the plasmid backbone, and merely consists of the target expression
      cassette and the bacterial origin of replication. Three different host/vector
      combinations were cultivated in a fed-batch fermentation process, comparing the
      progenitor strain JM108 to modified strains JM108murselect, hosting a plasmid
      either containing the aminoglycoside phosphotransferase which provides kanamycin
      resistance, or a marker-free variant of the same plasmid. The metabolic load
      exerted by expression of the aminoglycoside phosphotransferase was monitored by
      measuring ppGpp- and cAMP-levels. Moreover, we revealed that JM108 is deficient
      of the Lon protease and thereby refined the genotype of JM108. The main
      consequences of Lon-deficiency with regard to plasmid DNA production are
      discussed herein. Additionally, we found that the expression of the
      aminoglycoside phosphotransferase, conferring resistance to kanamycin, was very
      high in plasmid DNA producing processes that actually inclusion bodies were
      formed. Thereby, a severe metabolic load on the host cell was imposed,
      detrimental for overall plasmid yield. Hence, deleting the antibiotic resistance
      gene from the vector backbone is not only beneficial with regards to safety and
      potency of the end-product but also regarding the overall process performance.

PMID- 20138929
TI  - 3D-wound healing model: influence of morphine and solid lipid nanoparticles.
AB  - For efficient pain reduction in severe skin wounds, topically applied opioids may
      be a new option. Moreover, by stimulating keratinocyte migration opioids may also
      accelerate wound healing. Yet, conventional formulations failed to consistently
      provide sufficient pain control in patients which may be due to local drug
      degradation or insufficient concentrations at the target site. After having
      excluded major morphine glucuronidation by keratinocytes and fibroblasts, we next
      aimed for an optimised formulation. Since long intervals for painful wound
      dressing changes are intended, the formulations should allow for prolonged opioid
      release and should not impair the healing process. We developed morphine-loaded
      solid lipid nanoparticles (SLN, mean size about 180 nm), and tested improvement
      of wound closure in a new human-based 3D-wound healing model. Standardised wounds
      were induced by CO(2)-laser irradiation of reconstructed human full-thickness
      skin equivalents (EpiDermFT). Morphine, morphine-loaded and unloaded SLN
      accelerated reepithelialization. Keratinocytes almost completely covered the
      dermis equivalent after 4 days, which was not the case when applying the vehicle.
      In conclusion, acceleration of wound closure, low cytotoxicity and irritation as
      well as possible prolonged morphine release make SLN an interesting approach for
      innovative wound management.

PMID- 20138930
TI  - Design and prototyping of a chip-based multi-micro-organoid culture system for
      substance testing, predictive to human (substance) exposure.
AB  - Dynamic miniaturized human multi-micro-organ bioreactor systems are envisaged as
      a possible solution for the embarrassing gap of predictive substance testing
      prior to human exposure. A rational approach was applied to simulate and design
      dynamic long-term cultures of the smallest possible functional human organ units,
      human "micro-organoids", on a chip the shape of a microscope slide. Each chip
      contains six identical dynamic micro-bioreactors with three different micro
      organoid culture segments each, a feed supply and waste reservoirs. A liver, a
      brain cortex and a bone marrow micro-organoid segment were designed into each
      bioreactor. This design was translated into a multi-layer chip prototype and a
      routine manufacturing procedure was established. The first series of
      microscopable, chemically resistant and sterilizable chip prototypes was tested
      for matrix compatibility and primary cell culture suitability. Sterility and long
      term human cell survival could be shown. Optimizing the applied design approach
      and prototyping tools resulted in a time period of only 3 months for a single
      design and prototyping cycle. This rapid prototyping scheme now allows for fast
      adjustment or redesign of inaccurate architectures. The designed chip platform is
      thus ready to be evaluated for the establishment and maintenance of the human
      liver, brain cortex and bone marrow micro-organoids in a systemic
      microenvironment.

PMID- 20138931
TI  - Functional display of Pseudomonas and Burkholderia lipases using a translocator
      domain of EstA autotransporter on the cell surface of Escherichia coli.
AB  - Functional expression of the industrially important Pseudomonas and Burkholderia
      lipases, such as those from P. aeruginosa, B. cepacia and P. fluorescens, was
      achieved on the cell surface of Escherichia coli using the C-terminal
      translocator moiety (EstATu) of autotransporter protein (EstA) from P. putida. In
      particular, lipases which required a lipase-specific foldase (Lif) for their
      proper folding were for the first time displayed in the active form by
      coexpression of the Lif protein.

PMID- 20138932
TI  - G to A hypermutation of TT virus.
AB  - APOBEC3 proteins function as part of innate antiviral immunity and induce G to A
      hypermutation in retroviruses and hepatitis B virus (HBV) genomes. Whether
      APOBEC3 proteins affect viruses that replicate without a reverse transcription
      step is unknown. TT virus (TTV), known to present in serum of healthy individuals
      and HBV carriers, has a single-stranded circular DNA genome and replicates
      without reverse transcription. In this study, we examined 67 blood samples
      obtained from healthy individuals and HBV carriers and observed G to A
      hypermutation of genomes of TTV in both healthy individuals and HBV carriers.
      During ALT flare-up in HBV carriers, G to A hypermutation of HBV increased, but
      TTV genomes significantly decreased in number and hypermutated TTV genomes became
      undetectable. Our results show that hypermutated TTV exist in healthy individuals
      and HBV carriers and that TTV genomes were susceptible to immune reaction
      directed to HBV by interacting with APOBEC3 proteins.

PMID- 20138933
TI  - Polymorphisms of the BK virus subtypes and their influence on viral in vitro
      growth efficiency.
AB  - The major capsid protein, VP1, of the human polyomavirus BK (BKV) is structurally
      divided into five outer loops, referred to as BC, DE, EF, GH, and HI. The BC loop
      includes a short region, named the BKV subtyping region, spanning nucleotides
      1744-1812 and characterized by non-synonymous nucleotide polymorphisms that have
      been used to classify different strains of BKV into four subtypes. The aim of
      this study was to determine if the nucleotide changes clustered within the BKV
      subtyping region may influence the in vitro growth efficiency of the virus. We
      therefore infected the African Green Monkey kidney cell line Vero with four
      different viral strains (named BKV I, II, III, and IV) that contained the
      nucleotide sequences of the BKV subtypes within the same genomic background.
      Infected cells were followed for 59 days and viral replication was assessed at
      different time points by quantitative real-time PCR (Q-PCR). BKV I, II, and IV
      were successfully propagated over time in Vero cells, whereas BKV III viral loads
      progressively decreased during the infection course, demonstrating that the non
      synonymous nucleotide polymorphisms of subtype III confer a strong disadvantage
      for viral replication. Since subtype III differs from all the other subtypes at
      position 68 of the VP1, where Leu is replaced by Gln, we created viral strains
      bearing Gln at this position together with the polymorphisms of subtypes I, II,
      IV and tested their growth in Vero cells. Our results demonstrate that this amino
      acid substitution does not lower the replication efficiency of subtypes I, II,
      and IV. In conclusion, this study provides further insights to the importance of
      the BC loop of BKV in the virus life cycle. In addition, given the effect of the
      amino acid substitutions of the four BKV subtypes on infectious spread of the
      virus, our results suggest the need to investigate their potential association
      with BKV related complications.

PMID- 20138934
TI  - Shimoni bat virus, a new representative of the Lyssavirus genus.
AB  - During 2009, 616 bats representing at least 22 species were collected from 10
      locations throughout Kenya. A new lyssavirus, named Shimoni bat virus (SHIBV),
      was isolated from the brain of a dead Commerson's leaf-nosed bat (Hipposideros
      commersoni), found in a cave in the coastal region of Kenya. Genetic distances
      and phylogenetic reconstructions, implemented for each gene and for the
      concatenated alignment of all five structural genes (N, P, M, G and L),
      demonstrated that SHIBV cannot be identified with any of the existing species,
      but rather should be considered an independent species within phylogroup II of
      the Lyssavirus genus, most similar to Lagos bat virus (LBV). Antigenic reaction
      patterns with anti-nucleocapsid monoclonal antibodies corroborated these
      distinctions. In addition, new data on the diversity of LBV suggests that this
      species may be subdivided quantitatively into three separate genotypes. However,
      the identity values alone are not considered sufficient criteria for demarcation
      of new species within LBV.

PMID- 20138935
TI  - A mucoadhesive nanoparticulate system for the simultaneous delivery of
      macromolecules and permeation enhancers to the intestinal mucosa.
AB  - The feasibility of combining safe permeation enhancers in a mucoadhesive
      particulate system for the oral delivery of peptide drugs was investigated in
      this study. Polyelectrolyte complex nanoparticles (NPs) were prepared by ionic
      interaction of spermine (SPM) with polyacrylic acid (PAA) polymer. Cytotoxicity
      studies in Caco-2 monolayers revealed the safety of the delivery system in the
      concentration range used for permeation enhancement. The cellular transport of
      fluorescein isothiocyanate dextran (FD4) showed higher permeation enhancing
      profiles of SPM-PAA NPs, as compared to SPM solution or PAA NPs prepared by ionic
      gelation with MgCl(2) (Mg-PAA NPs). These permeation enhancing effects were
      associated with a reversible decrease in TEER values, suggesting a paracellular
      permeation pathway by reversible opening of the tight junctions. Furthermore,
      confocal microscopy results revealed strong association of the NPs prepared using
      fluorescence labeled PAA to Caco-2 cells. The permeation enhancing properties of
      SPM-PAA NPs were further evaluated in vivo after oral administration to rats,
      using FD4 and calcitonin as models of poorly permeating drugs. Confocal
      microscopy images of rats' small intestine confirmed previous findings in Caco-2
      cells and revealed a strong and prolonged penetration of FD4 from the mucosal to
      the basolateral side of the intestinal wall. In addition, the proposed NPs were
      efficient in improving the oral absorption of calcitonin, as evidenced by the
      significant and prolonged reduction of the blood calcemia in rats.

PMID- 20138936
TI  - Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid
      DNA carried by RGD-modified crosslinked polyplex micelles.
AB  - Disulfide crosslinked polyplex micelles with RGD peptides were formed through ion
      complexation of thiolated c(RGDfK)-poly(ethylene glycol)-block-poly(L-lysine)
      (c(RGDfK)-PEG-P(Lys-SH)) and plasmid DNA encoding sFlt-1 and tested for their
      therapeutic effect in BxPC3 pancreatic adenocarcinoma tumor bearing mice. These
      micelles, systemically injected, demonstrated significant inhibition of tumor
      growth up to day 18, as a result of the antiangiogenic effect that was confirmed
      by vascular density measurements. Significant therapeutic activity of the 15%
      crosslinked micelle (c(RGDfK)-PEG-P(Lys-SH15)) was achieved by combined effect of
      increased tumor accumulation, interaction with endothelial cells and enhanced
      intracellular uptake through receptor-mediated endocytosis. These results suggest
      that RGD targeted crosslinked polyplex micelles can be effective plasmid DNA
      carriers for antiangiogenic gene therapy.

PMID- 20138937
TI  - Functionalization of poly(amidoamine) dendrimers with hydrophobic chains for
      improved gene delivery in mesenchymal stem cells.
AB  - A new family of gene delivery vectors is synthesized consisting of a medium-size
      generation PAMAM dendrimer (generation 5, with amine termini) core randomly
      linked at the periphery to hydrophobic chains that vary in length (12 to 16
      carbon alkyl chains) and number (from 4.2 to 9.7 in average). The idea subjacent
      to the present work is to join the advantages of the cationic nature of the
      dendrimer with the capacity of lipids to interact with biological membranes.
      Unlike other amphiphilic systems designed for the same purpose, where the
      hydrophobic and hydrophilic moieties coexist in opposite sides, the present
      vectors have a hydrophilic interior and a hydrophobic corona. The vectors are
      characterized in respect to their ability to neutralize, bind and compact plasmid
      DNA (pDNA). The complexes formed between the vectors and pDNA are analyzed
      concerning their size, zeta-potential, resistance to serum nucleases, capacity of
      being internalized by cells and transfection efficiency. These new vectors show a
      remarkable capacity for mediating the internalization of pDNA with minimum
      cytotoxicity, being this effect positively correlated with the -CH(2)- content
      present in the hydrophobic corona. Gene expression in MSCs, a cell type with
      relevancy in the regenerative medicine clinical context, is also enhanced using
      the new vectors but, in this case, the higher efficiency is shown by the vectors
      containing the smallest hydrophobic chains.

PMID- 20138938
TI  - Silk fibroin encapsulated powder reservoirs for sustained release of adenosine.
AB  - Due to its unique properties, silk fibroin was studied as a biodegradable polymer
      vehicle for sustained, local delivery of the anticonvulsant adenosine from
      encapsulated reservoirs. Silk is a biologically derived protein polymer that is
      biocompatible, mechanically strong and degrades to non-toxic products in vivo. To
      achieve local, sustained, controlled adenosine release from fully degradable
      implants, solid adenosine powder reservoirs were coated with silk fibroin.
      Material properties of the silk coating including thickness, crystallinity and
      morphology were investigated to assess the relationships between silk coating
      biomaterial features and adenosine release from silk encapsulated reservoirs.
      Reservoir coating thickness was varied through manipulation of the silk coating
      solution concentration and number of coatings applied. Release studies were also
      performed in proteinase type XIV to model the effects of degradation. Increasing
      the barrier to diffusion, either by increasing coating thickness or crystallinity
      was found to delay adenosine burst, decrease average daily release rate, and
      increase duration of release. In the case of encapsulated reservoirs coated with
      eight layers of 8% (w/v) silk, a linear release profile was observed and
      adenosine release was sustained for 14days. The ability to achieve nearly
      constant release for 2weeks for adenosine via control of the silk coating
      suggests these encapsulated reservoirs represent a novel system for delivering
      adenosine. We anticipate that this approach could also be extended to other
      implant needs and small-molecule drugs to treat a range of clinical needs.

PMID- 20138939
TI  - RNA interference by nanofiber-based siRNA delivery system.
AB  - SiRNA delivery has found useful applications particularly as therapeutic agents
      against genetic diseases. Currently, the delivery of siRNA typically takes the
      form of nanoparticles. In order to expand the applications of these potent but
      labile molecules for long-term use required by tissue engineering and
      regenerative medicine, alternative delivery vehicles are required. This work
      presents a scaffold-mediated approach to siRNA delivery. By encapsulating siRNA
      within polycaprolactone (PCL) nanofibers (300-400nm in diameter) controlled
      release of intact siRNA could be achieved for at least 28days under physiological
      conditions. The successful transfection of HEK 293 cells with GAPDH siRNA
      released from fibrous scaffolds at day 5, 15 and 30 demonstrated that the
      encapsulated molecules remained bioactive throughout the period of sustained
      release, providing silencing efficiency of 61-81% that was comparable to
      conventional siRNA transfection. Direct seeding of cells on these biofunctional
      scaffolds, with and without transfection reagent, demonstrated enhanced cellular
      uptake and efficient GAPDH gene-silencing. This work demonstrates the potential
      of nanofibrous scaffold-mediated siRNA delivery for long-term gene-silencing
      applications. The combination of topographical features provided by nanofibrous
      scaffolds may provide synergistic contact guidance and biochemical signals to
      mediate and support cellular development in regenerative medicine.

PMID- 20138940
TI  - Therapeutic cell delivery and fate control in hydrogels and hydrogel hybrids.
AB  - Hydrogels are synthetic or natural polymer networks that closely mimic native
      extracellular matrices. As hydrogel-based vehicles are being increasingly
      employed in therapeutic cell delivery, two inherent traits of most common
      hydrogels, namely low cell affinity and high cell constraint, have significantly
      drawn the attention of biomedical community. These two properties lead to the
      unfavourable settlement of anchorage-dependent cells (ADCs) and unsatisfactory
      cell delivery or tissue formation in hydrogel matrices. Tissue engineers have
      correspondingly made many efforts involving chemical modification or physical
      hybridisation to facilitate ADC settlement and promote tissue formation. On the
      other hand, these two 'bio-inert' characteristics have particularly favoured
      oncological cell therapists, who expect to utilize hydrogels to provide
      sufficiently high confinement of the delivered cells for anti-cancer purposes. In
      general, control of cell fate and behaviours in these three-dimensional (3D)
      microenvironments has become the central aim for hydrogel-mediated cell delivery,
      towards which various models based on hydrogels and their hybrids have emerged.
      In this paper, we will first review the development of strategies aiming to
      overcome the aforementioned two 'shortcomings' by (i) establishing ADC survival
      and (ii) creating space for tissue formation respectively, and then introduce how
      people take advantage of these 'disadvantages' of hydrogel encapsulation for
      (iii) an enhanced confinement of cell motion.

PMID- 20138941
TI  - Can people make healthy changes to their diet and maintain them in the long term?
      A review of the evidence.
AB  - A diet high in saturated fat and low in fibre, fruit and vegetable intake is a
      risk factor in chronic conditions and in overall mortality. Current records show
      little long term dietary change in the general population. This review examined
      evidence for long term successful dietary changes in the daily intake of fat,
      fruit, vegetables and fibre. Eight randomized control trials with 17 intervention
      arms were included. There were 62,565 participants (89% women) randomized to
      intervention or active control group. Participants in most of the intervention
      groups were able to make changes in the daily intake of fat (reduction range: 1.6
      13.7%) fruit and vegetables (increase range: 0.2-4.6 svgs/day) and fibre
      (increase range: 0.9-13.5 g/day) as measured at 12 months. The magnitude of these
      changes diminished thereafter with each consecutive year following intervention
      with the exception of Polyp Prevention Trial where the changes were maintained
      for 4 years of trial duration. A well designed intervention motivated
      participants to make and maintain successful dietary changes in terms of
      reduction of daily fat intake and increased intake of fruit, vegetables and fibre
      over the course of 12 months. The differences in dietary intake as compared with
      baseline diminished steadily with each subsequent year of intervention unless the
      intervention programme remained highly intensive.

PMID- 20138942
TI  - Familiarity changes expectations about fullness.
AB  - Expected satiation (the extent to which a food is expected to deliver fullness)
      is an excellent predictor of self-selected portion size (kcal). Here, we explored
      the prospect that expected satiation changes over time. Fifty-eight participants
      evaluated expected satiation in eight test foods (including two 'candidate'
      foods: sushi and muesli) and reported how often they consumed each food. In one
      of the candidate foods (sushi), and across other test foods, expected satiation
      increased with familiarity. Together, these findings are considered in the
      context of 'satiation drift' - the hypothesis that foods are expected to deliver
      poor satiation until experience teaches us otherwise.

PMID- 20138943
TI  - Comparison of 150-mm versus 100-mm visual analogue scales in free living adult
      subjects.
AB  - The aim of this study was to verify whether appetite sensation scores obtained
      from 150-mm visual analogue scales (VAS) can be compared to those obtained from
      100-mm scales. On one occasion, using a within-subject design, 25 participants
      (mean age: 42.2 + or - 13.3 years, mean body mass index: 22.9 + or - 2.3 kg/m(2))
      recorded their appetite sensations before lunch, and at five additional time
      points during the postprandial period. At each time point, both VAS (150 mm and
      100 mm) were used to record desire to eat, hunger, fullness, satiety, and
      prospective food consumption. The VAS in the same booklet were completed
      immediately one after the other in a randomized order to eliminate the order
      effect. We observed that the immediate, successive completion of questionnaires
      varying in length resulted in no significant difference in appetite markers, with
      a strong linear relationship between the two tools (r from 0.80 to 0.98, P<0.01).
      We conclude that VAS scores obtained from 150-mm to 100-mm length scales are
      interchangeable, both before and in response to a meal.

PMID- 20138944
TI  - Emotional eating, depressive symptoms and self-reported food consumption. A
      population-based study.
AB  - We examined the associations of emotional eating and depressive symptoms with the
      consumption of sweet and non-sweet energy-dense foods and vegetables/fruit, also
      focusing on the possible interplay between emotional eating and depressive
      symptoms. The participants were 25-64-year-old Finnish men (n=1679) and women
      (n=2035) from the FINRISK 2007 Study (DILGOM substudy). The Three-Factor Eating
      Questionnaire-R18, Center for Epidemiological Studies Depression Scale, and a 132
      item Food Frequency Questionnaire were used. Emotional eating and depressive
      symptoms correlated positively (r=0.31 among men and women), and both were
      related to a higher body mass. Emotional eating was related to a higher
      consumption of sweet foods in both genders and non-sweet foods in men
      independently of depressive symptoms and restrained eating. The positive
      associations of depressive symptoms with sweet foods became non-significant after
      adjustment for emotional eating, but this was not the case for non-sweet foods.
      Depressive symptoms, but not emotional eating, were related to a lower
      consumption of vegetables/fruit. These findings suggest that emotional eating and
      depressive symptoms both affect unhealthy food choices. Emotional eating could be
      one factor explaining the association between depressive symptoms and consumption
      of sweet foods, while other factors may be more important with respect to non
      sweet foods and vegetables/fruit.

PMID- 20138945
TI  - Prediction of daily fruit and vegetable consumption among overweight and obese
      individuals.
AB  - The purpose of this study is twofold: to identify the determinants of daily fruit
      and vegetable (F&V) consumption and the moderators of the intention-behaviour
      relationship. A sample of 225 overweight or obese adults completed a TPB
      questionnaire. F&V behaviour was assessed at baseline and three months later.
      Statistical analyses revealed that past behaviour, perceived behavioural control
      (PBC) and age were significant predictors of daily F&V consumption. In addition,
      intention was found to interact with anticipated regret. Interventions should
      encourage the development of habit and PBC. However, the age and level of
      anticipated regret of the targeted population should be considered when designing
      interventions.

PMID- 20138946
TI  - Peptide DV-28 amide: An inhibitor of bradykinin-induced arterial smooth muscle
      relaxation encoded by Bombina orientalis skin kininogen-2.
AB  - Skin kininogens from bombinid toads encode an array of bradykinin-related
      peptides and one such kininogen from Bombina maxima also encodes the potent
      bradykinin B2-receptor antagonist, kinestatin. In order to determine if the skin
      secretion of the closely-related toad, Bombina orientalis, contained a bradykinin
      inhibitory peptide related to kinestatin, we screened reverse phase HPLC
      fractions of defensive skin secretion using a rat tail artery smooth muscle
      preparation. A fraction was located that inhibited bradykinin-induced relaxation
      of the preparation and this contained a peptide of 3198.5Da as determined by
      MALDI-TOF MS. Automated Edman degradation of this peptide established the
      identity of a 28-mer as: DMYEIKGFKSAHGRPRVCPPGEQCPIWV, with a disulfide-bridge
      between Cys(18) and Cys(24) and an amidated C-terminal Val residue. Peptide DV-28
      was found to correspond to residues 133-160 of skin pre-kininogen-2 of B.
      orientalis that also encodes two copies of (Thr(6))-bradykinin. The C-terminal
      residue, Gly-161, of the precursor open-reading frame, acts as the C-terminal
      amide donor of mature DV-28. DV-28 amide thus represents a new class of
      bradykinin inhibitor peptide from amphibian skin secretion.

PMID- 20138947
TI  - Identification of gonadotropin-inhibitory hormone in the zebra finch (Taeniopygia
      guttata): Peptide isolation, cDNA cloning and brain distribution.
AB  - Two novel RFamide peptides, kisspeptins and gonadotropin-inhibitory hormone
      (GnIH) are neuropeptides that appear critical in the regulation of the
      reproductive neuroendocrine axis. GnIH was first identified in avian brain,
      however, kisspeptins have not been identified in birds. To determine
      biochemically the presence of kisspeptins and GnIH in the zebra finch, a study
      was conducted to isolate these two peptides from zebra finch brain. Peptides were
      isolated by immunoaffinity purification and only one peptide was characterized by
      mass spectrometry. This peptide was confirmed to be a 12-amino acid sequence with
      RFamide at its C-terminus; its sequence is SIKPFSNLPLRFamide (zebra finch GnIH).
      By this approach, however, identification of kisspeptin from zebra finch brain
      was not achieved. Cloned zebra finch GnIH precursor cDNA encoded three peptides
      that possess characteristic LPXRFamide (X=L or Q) motifs at the C-termini. In
      situ hybridization and immunohistochemical analysis revealed the cellular
      localization of zebra finch GnIH mRNA and peptide in the paraventricular nucleus
      and the dorsomedial nucleus of the hypothalamus. Fluorescent immunohistochemistry
      with confocal microscopy indicated that GnIH-immunoreactive (ir) fibers are very
      close appositions with gonadotropin-releasing hormone-I (GnRH-I) cells.
      Furthermore GnIH-ir nerve fibers were widely distributed in the multiple brain
      regions including the septum, preoptic area, median eminence, optic tectum and
      median eminence. The prominent fibers were seen in the ventral tegmental area,
      midbrain central gray and dorsal motor nucleus of the vagus in the medulla. Thus,
      GnIH may participate in not only neuroendocrine functions but also regulation of
      motivation for social behavior and autonomic mechanisms.

PMID- 20138948
TI  - Functional neuroimaging of minocycline's effect in a patient with schizophrenia.

PMID- 20138949
TI  - A genetic schizophrenia-susceptibility region located between the ANKK1 and DRD2
      genes.
AB  - BACKGROUND: The gene coding for the D2 dopamine receptor (DRD2) is considered to
      be one of the most pertinent candidate genes in schizophrenia. However, genetic
      studies have yielded conflicting results whereas the promising TaqIA
      variant/rs1800497 has been mapped in a novel gene, ANKK1. METHODS: We
      investigated eleven single nucleotide polymorphisms (SNPs) spanning the DRD2 and
      ANKK1 genes, using both a case-control association study comparing 144
      independent patients to 142 matched healthy subjects, and a transmission
      disequilibrium test in 108 trios. This classical genetic study was coupled with a
      cladistic phylogeny-based association test of human variants, and with an
      interspecies evolution study of ANKK1. RESULTS: Case-control study, followed by a
      108 trios family-based association analysis for replication, revealed an
      association between schizophrenia and the ANKK1 rs1800497 (p=0.01, Odds
      Ratio=1.5, 95% Confidence Interval=1.1-2.2), and the intergenic rs2242592
      (p=2.10(-4), OR=1.8, 95%CI=1.3-2.5). A significant SNP-SNP interaction was also
      found (p<10(-5), OR=2.0, 95%CI=1.6-2.5). The phylogeny-based association test
      also identified an association between both these polymorphisms and
      schizophrenia. Finally, interspecies comparison of the sequences from chimpanzee,
      orangutan, rhesus macaque and human species suggested specific involvement of
      ANKK1 in the human lineage. CONCLUSIONS: Intergenic rs2242592 appears to be
      involved in the genetic vulnerability to schizophrenia, whereas the ANKK1
      rs1800497 appears to have a modifying rather than causative effect. Finally,
      ANKK1 may be a specific human lineage-trait involved in a specific human disease,
      schizophrenia.

PMID- 20138950
TI  - Evaluation of tolerable levels of dietary quercetin for exerting its
      antioxidative effect in high cholesterol-fed rats.
AB  - The tolerable level of dietary quercetin for exerting its antioxidative effect
      was evaluated in high cholesterol-fed rats, using quercetin-containing diets (31
      1260 mg quercetin/kg body weight/day) and onion diets (19-94 mg quercetin
      aglycone equivalent/kg body weight/day), from the viewpoint of a safety
      assessment. After feeding for 4 weeks, the urinary 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG) levels of the quercetin-containing diet groups fed more
      than 157 mg quercetin/kg body weight/day were higher than the group fed a
      quercetin-free diet, although the plasma quercetin metabolite levels and plasma
      antioxidative activity were elevated depending on the amounts of quercetin or
      onion diet intake. No significant effect on body weight gain by quercetin
      containing diets or onion diets was observed. However, ratios of the liver and
      kidney weights to the body weight were significantly increased in the quercetin
      containing diet groups fed more than 314 mg and 157 mg quercetin/kg body
      weight/day, respectively, and in the onion diet groups fed more than 47 mg
      quercetin aglycone equivalent/kg body weight/day. These results indicated that
      the tolerable level for dietary quercetin for exerting its antioxidative effect
      was between 126 and 157 mg/kg/day for the quercetin diet and between 19 and 34
      mg/kg/day for the onion diet.

PMID- 20138951
TI  - Mould incidence and mycotoxin contamination in maize kernels from Swat Valley,
      North West Frontier Province of Pakistan.
AB  - Mould incidence and aflatoxin B1 (AFB1) and ochratoxin A (OTA) contamination as
      well as proximate composition and minerals content of maize kernels from Swat
      Valley, North West Frontier Province of Pakistan was studied during the year,
      2007. Results indicated that the mean moisture content of the kernels was within
      the recommended safe storage levels of 15%. Across the whole valley, Aspergillus,
      Fusarium, Penicillium and Rhizopus were the most predominant fungal genera
      identified and amongst the mycotoxigenic species, Aspergillus flavus had the
      highest incidence. AFB1 content ranged from none to 30.92 microg/kg with the
      average values of 14.94 and 16.22 microg/kg for Upper and Lower Swat regions,
      respectively. Similar trend was observed for OTA with the contamination level
      ranged from <0.001 to 7.32 microg/kg. A significant numbers of samples contained
      AFB1 and OTA levels above the safe limits as recommended by the USFDA and EU but
      on the average the results were within the safe limit. These results indicate
      that maize consumers in Swat Valley may be exposed to the danger of aflatoxins
      and ochratoxins poisoning. Thus, there is a need for policy makers to establish
      and enforce maize quality standards and regulations related to moulds and
      mycotoxins across the area.

PMID- 20138952
TI  - Maternal fenvalerate exposure during pregnancy persistently impairs testicular
      development and spermatogenesis in male offspring.
AB  - Fenvalerate, a widely used pyrethroid insecticide, has been associated with poor
      semen quality. As yet, little is known about the effects of prenatal fenvalerate
      exposure on testicular development. The present study investigated the effects of
      prenatal fenvalerate exposure on testicular development and spermatogenesis. The
      pregnant mice were administered fenvalerate (30 mg/kg) by gavage daily from
      gestational day (gd) 13 to gd 18. The weights of testes and epididymides were
      significantly decreased in mice whose mothers were exposed to fenvalerate during
      pregnancy. Importantly, maternal fenvalerate exposure during pregnancy markedly
      decreased the number of mature seminiferous tubules (stages VII and VIII) in
      testes of adult male offspring. In addition, maternal fenvalerate exposure during
      pregnancy significantly reduced the number of epididymal spermatozoa in adult
      male offspring. Additional experiments showed that the level of serum
      testosterone (T) was significantly decreased in male fetuses whose mothers were
      exposed to fenvalerate during pregnancy. Correspondingly, mRNA and protein levels
      of P450(17alpha), a T synthetic enzyme, were significantly decreased in fetal
      testes. Moreover, the disruptive effect of prenatal fenvalerate exposure on
      testicular T synthesis was irreversible. In conclusion, prenatal fenvalerate
      exposure irreversibly impairs testicular development and spermatogenesis at least
      into early adulthood.

PMID- 20138953
TI  - Protective effect of fermented sea tangle against ethanol and carbon
      tetrachloride-induced hepatic damage in Sprague-Dawley rats.
AB  - Sea tangle has long been used as Korean folk remedy to promote material health,
      and is one of the popular dietary supplement. This study was designed to evaluate
      the protective effect of fermented sea tangle (FST) against ethanol and carbon
      tetrachloride (CCl(4))-induced hepatotoxicity in rats. Sprague-Dawley rats were
      orally treated with FST (25, 250, 2500 mg/kg/day) with administration of ethanol
      (5 mL/kg) for 13 weeks and the single intraperitoneal (i.p.) dose of 50% CCl(4)
      (5 mL/kg/day, CCl(4) in olive oil) at 12 week, and repeated i.p. dose of 20%
      CCl(4) (2 mL/kg/day) for 1 week. Hepatotoxicity was evaluated by measuring the
      serum levels of glutamic pyruvate transaminase (GPT), gamma glutamyl
      transpeptidase (gamma-GT) and malondialdehyde (MDA) as well as the tissue levels
      of antioxidant enzyme such as superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPx). Ethanol and CCl(4)-induced the rat liver damage,
      and significantly increased (p<0.05) the GPT, gamma-GT and MDA levels, and
      decreased the SOD, CAT and GPx levels. However, treatment with FST could decrease
      serum GPT, gamma-GT, and MDA levels significantly in plasma, and increase the
      activities of SOD, CAT, and GPx in liver tissues compared with ethanol and CCl(4)
      treated group.

PMID- 20138954
TI  - Comparative effects of 3,4-methylenedioxymethamphetamine and 4
      methylthioamphetamine on rat liver mitochondrial function.
AB  - Ecstasy, which is used as a recreational drug, is a common street name for 3, 4
      methylenedioxymethamphetamine (MDMA). Another drug of abuse chemically related,
      though less common than MDMA, is the amphetamine derivative 4
      methylthioamphetamine (MTA). MDMA and MTA induce different systemic and organ
      specific effects, including neurotoxicity, hyperthermia, nephrotoxicity,
      cardiotoxicity and hepatotoxicity. Therefore, it is clear that MDMA and MTA are
      responsible for inducing organ toxicity. The mechanisms underlying MDMA and MTA
      induced hepatotoxicity are multifactorial, and therefore not completely
      understood. Recent findings indicate interference with cellular bioenergetics as
      an important toxicological feature of ecstasy. However, less is known about the
      involvement of mitochondria in MTA-induced hepatotoxicity. Thus, we compared the
      direct influence of MDMA and MTA on rat liver mitochondrial function
      [mitochondrial permeability transition (MPT), mitochondrial oxidative stress, and
      mitochondrial bioenergetics]. It was shown that MTA (from 0.025 up to 0.1mM) was
      more potent than MDMA (from 0.2 up to 0.5mM) in decreasing the sensitivity of rat
      liver mitochondria to MPT. However, higher concentrations of MTA (from 0.5 up to
      2mM) were highly toxic to mitochondria. MTA simultaneously increased H(2)O(2)
      production in a monoamine oxidase (MAO)-dependent way, and uncoupled and
      inhibited mitochondrial respiration. In contrast, MDMA had only limited or no
      effects on these mitochondrial parameters. According to these results, it is
      possible to postulate that, depending on the concentration, MTA can potentially
      be more efficient in its effects on liver mitochondria than MDMA and, also, that
      its harmful effects may contribute to its hepatotoxicity.

PMID- 20138955
TI  - DNA-hydrolyzing activity of IgG antibodies from the sera of patients with tick
      borne encephalitis.
AB  - DNase autoantibodies (Abzs) can be found in the blood of patients with several
      autoimmune diseases, while the blood of healthy donors or patients with diseases
      with an insignificant disturbance of the immune status does not contain DNase
      Abzs. Here we present the first analysis of the DNase Abzs activity in the
      patients with tick-borne encephalitis (TBE). Several strict criteria have been
      applied to show that the DNase activity is an intrinsic property of IgGs from the
      sera of TBE patients but not from healthy donors. The relative activity of IgGs
      has been shown to vary extensively from patient to patient, but most of the
      preparations (91%) had detectable levels of the DNase activity. Polyclonal DNase
      IgGs were not active in the presence of EDTA or after a dialysis against EDTA,
      but could be activated by several externally added metal ions, with the level of
      activity decreasing in the order Mn(2+) + Ca(2+) > or = Mn(2+)+ Mg(2+) > or =
      Mn(2+) > or = Mg(2+) + Ca(2+) > or = Co(2+) > or = Mg(2+) > Ca(2+), while K(+),
      Na(+), Ni(2+), Zn(2+), and Cu(2+) did not stimulate DNA hydrolysis. Affinity
      chromatography on DNA-cellulose separated the DNase IgGs into many subfractions
      with various affinities for DNA and very different levels of the relative
      activity. Possible reasons for catalytic diversity of polyclonal human Abzs are
      discussed.

PMID- 20138956
TI  - Ammonia metabolism, the brain and fatigue; revisiting the link.
AB  - This review addresses the ammonia fatigue theory in light of new evidence from
      exercise and disease studies and aims to provide a view of the role of ammonia
      during exercise. Hyperammonemia is a condition common to pathological liver
      disorders and intense or exhausting exercise. In pathology, hyperammonemia is
      linked to impairment of normal brain function and the onset of the neurological
      condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise
      due to a diminished capacity for removal via the liver and lead to increased
      exposure of organs, such as the brain, to the toxic effects of ammonia. High
      levels of brain ammonia can lead to deleterious alterations in astrocyte
      morphology, cerebral energy metabolism and neurotransmission, which may in turn
      impact on the functioning of important signalling pathways within the neuron.
      Such changes are believed to contribute to the disturbances in neuropsychological
      function, in particular the learning, memory, and motor control deficits observed
      in animal models of liver disease and also patients with cirrhosis.
      Hyperammonemia in exercise occurs as a result of an increased production by
      contracting muscle, through adenosine monophosphate (AMP) deamination (the purine
      nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to
      oxidation. Plasma concentrations of ammonia during exercise often achieve or
      exceed those measured in liver disease patients, resulting in increased cerebral
      uptake. In this article we propose that exercise-induced hyperammonemia may lead
      to concomitant disturbances in brain function, potentially through similar
      mechanisms underpinning pathology, which may impact on performance as fatigue or
      reduced function, especially during extreme exercise.

PMID- 20138957
TI  - Effects of high-dose chemotherapy on bone marrow multipotent mesenchymal stromal
      cells isolated from lymphoma patients.
AB  - OBJECTIVE: High-dose chemotherapy (HDCT) followed by autologous stem cell
      transplantation is a widely applied treatment for hematological and autoimmune
      diseases. Little is known about the effects of this therapy on multipotent
      mesenchymal stromal cells (MSCs). We aimed to characterize, morphologically and
      functionally, MSCs isolated from bone marrow aspirates of patients after HDCT.
      MATERIALS AND METHODS: We studied 12 consecutive lymphoma patients submitted to
      BEAM conditioning regimen followed by autologous stem cell transplantation 28 to
      1836 days before the sample collection. Thirteen normal donors were used as
      control. MSCs were isolated by adherence to plastic and expanded ex vivo by
      culture in flasks containing alpha-minimum essential medium plus 15% fetal bovine
      serum. RESULTS: The cell population isolated showed a typical MSC morphology,
      immunophenotype, and differentiation capacity into adipogenic, osteogenic, and
      chondrogenic lineages. The MSCs obtained from patients with Hodgkin's disease and
      non-Hodgkin's lymphoma showed decreased fibroblastoid colony-forming unit count
      (p = 0.023) and increased doubling time (p = 0.031) related to the control group.
      The total cell expansion of MSCs from normal subjects was marginally superior to
      the patient group (p = 0.064). There were no differences in gene expression
      profile, MSCs plasticity, or hematopoiesis support capability between control and
      patient group. CONCLUSIONS: Results suggest that HDCT applied to lymphoma
      patients damaged MSCs, which was demonstrated by their reduced clonogenic
      potential, doubling time, and cell expansion rates when compared to controls.

PMID- 20138958
TI  - Iodine induces apoptosis via regulating MAPKs-related p53, p21, and Bcl-xL in
      thyroid cancer cells.
AB  - Thyroid cancer is the most common endocrine malignancy and exhibits the full
      range of malignant behaviors from the relatively indolent occult differentiated
      thyroid cancer to uniformly aggressive and lethal anaplastic thyroid cancer.
      Iodine is a well known key element in thyroid normal function maintenance and
      thyroid cancer development. However, the effects induced by iodine and the
      molecular mechanisms involved remain poorly understood in thyroid cancer. We
      investigated the apoptotic effect of iodine on three different subtypes of
      thyroid cancer cells. We observed that apoptosis induced by iodine was
      mitochondrial-mediated. Iodine treatment decreased the level of mutant p53
      including the R273H mutant that possesses anti-apoptotic features, but increased
      the p21 level. Surprisingly, high doses of iodine promoted instead of suppressed
      the expression of anti-apoptotic protein Bcl-xL expression. Moreover, iodine
      transiently activated the subfamily members of mitogen activated protein kinases
      (MAPKs) (ERK1/2, p38 and JNK1/2) which contribute to modulate p53, p21 and Bcl-xL
      expression. The further results showed the three subfamily members of MAPKs all
      worked as anti-apoptotic factors. Collectively, iodine-induced apoptotic pathway
      is involved in the activation of MAPKs-related p21, Bcl-xL and mutant p53
      regulation. The findings provide solid molecular evidence to explain the
      potential pathway for iodine to influence thyroid cancer development. It may also
      reveal some novel molecular targets for the treatment of thyroid cancer.

PMID- 20138959
TI  - Membrane receptors: structure and function of the relaxin family peptide
      receptors.
AB  - The receptors for members of the relaxin peptide family have only recently been
      discovered and are G-protein-coupled receptors (GPCRs). Relaxin and insulin-like
      peptide 3 (INSL3) interact with the leucine-rich-repeat-containing GPCRs (LGRs)
      LGR7 and LGR8, respectively. These receptors show closest similarity to the
      glycoprotein hormone receptors and contain large ectodomains with 10 leucine-rich
      repeats (LRRs) but are unique members of the LGR family (class C) as they have an
      LDL class A (LDLa) module at their N-terminus. In contrast, relaxin-3 and INSL5
      interact with another class of type I GPCRs which lack a large ectodomain, the
      peptide receptors GPCR135 and GPCR142, respectively. These receptors are now
      classified as relaxin family peptide (RXFP) receptors, RXFP1 (LGR7), RXFP2
      (LGR8), RXFP3 (GPCR135) and RXFP4 (GPCR142). This review outlines the
      identification of the peptides and receptors, their expression profiles and
      physiological roles and the functional interactions of the peptides with their
      unique receptors.

PMID- 20138960
TI  - Role of melanocortin receptor accessory proteins in the function of zebrafish
      melanocortin receptor type 2.
AB  - In this paper, we identify three different MRAPs in zebrafish, zfMRAP1, zfMRAP2a
      and zfMRAP2b, and demonstrate that zfMC2R is not functional in the absence of
      MRAP expression. ZfMRAP1 expression was restricted to adipose tissue and the
      anterior kidney whereas MRAP2a and MRAP2b were expressed in all the tissues
      tested. Quantification of surface receptor and immunofluorescence studies
      indicated that the receptor is unable to translocate to membrane in the absence
      of MRAP isoforms. MRAP1 and MRAP2b are localized in the plasma membrane in the
      absence of zfMC2R expression but MRAP2b is retained in perinuclear position.
      MRAP1 and MRAP2a displayed an equivalent translocation capacity to the membrane
      of zfMC2R but only zfMRAP1 expression led to intracellular cAMP increases after
      ACTH stimulation. ZfMRAP2b had no effect on zfMC2R activity but both zfMRAP2
      isoforms enhanced the zfMRAP1-assisted cAMP intracellular increase, suggesting an
      interaction between zfMRAP1 and zfMRAP2s when regulating zfMC2R activity.

PMID- 20138961
TI  - Inhibitory effect of pituitary adenylate cyclase activating polypeptide on the
      initial stages of rat follicle development.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is transiently
      expressed in preovulatory follicles of different species and positively affects
      parameters correlated with the ovulatory process. It has also been shown to be
      expressed in the interstitial tissue and in interstitial glandular cells in the
      proximity of primordial and preantral follicles. The aim of the present study was
      to investigate whether PACAP influences the recruitment of primordial follicles
      and the growth and differentiation of preantral follicles. Rat ovaries from 2-day
      old animals were cultured for 5 days in the presence of PACAP. This treatment
      significantly inhibited the primordial to primary follicle transition. PACAP
      inhibited granulosa cell proliferation without affecting cell viability. PACAP
      also inhibited the growth of isolated preantral follicles cultured under basal
      conditions or in the presence of follicle-stimulating hormone (FSH). These
      results suggest that PACAP is significantly involved in the cyclic recruitment of
      primordial follicles and in the FSH-dependent growth of preantral follicles.

PMID- 20138962
TI  - Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer
      cells.
AB  - Estrogens are structurally related steroids that regulate important physiological
      processes. 17beta-estradiol (E2) is reversibly oxidized to estrone (E1) and both
      E2 and E1 can be irreversibly converted to estriol (E3), which also originates
      directly from androstenedione. The action of E2 has been traditionally explained
      by the binding to the estrogen receptor (ER) alpha and ER beta, however the G
      protein-coupled receptor (GPR) 30 has been recently involved in the rapid
      signaling triggered by estrogens. Although the role of E2 in the development of
      breast cancer has been largely documented, the contribution of E3 still remains
      to be completely evaluated. Here, we demonstrate for the first time that E3 acts
      as a GPR30 antagonist since it was able to inhibit the GPR30-mediated responses
      such as the rapid ERK activation, the up-regulation of target genes like c-fos
      and connective tissue growth factor, the proliferative effects observed in ER
      negative SkBr3 cells.

PMID- 20138963
TI  - Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism.
AB  - TSH receptor (TSHR) germline mutations occur as activating mutations in familial
      non-autoimmune hyperthyroidism (FNAH) or sporadic non-autoimmune hyperthyroidism
      (SNAH). Up to date 17 constitutively activating TSHR mutations have been reported
      in 24 families with FNAH. The diagnosis of FNAH should be considered in cases
      with a positive family history, early onset of hyperthyroidism, goiter, absence
      of clinical stigmata of autoimmunity and recurrent hyperthyroidism. Moreover, 14
      subjects with sporadic non-autoimmune hyperthyroidism and 10 different TSH
      receptor germline mutations have been reported. The main characteristic of SNAH
      is a negative family history. Additional consequences of prolonged neonatal
      hyperthyroidism (mental retardation, speech disturbances and craniosynostosis)
      have often been reported in SNAH. No genotype-phenotype relationship has been
      reported in patients with germline TSHR mutations. There is no association of in
      vitro activities determined by linear regression analysis (LRA) and several
      clinical indicators of hyperthyroidism activity for SNAH. However, the comparison
      of the LRA values of sporadic TSHR mutations with LRA values of familial TSHR
      mutations does show a significantly higher median LRA value for sporadic as
      compared to familial autosomal dominant hyperthyroidism. This finding is in line
      with the clinical impression of a more active clinical course in patients with
      SNAH. However, additional genetic, constitutional or environmental factors are
      most likely responsible for the phenotypic variations of the disease and the lack
      of correlation between in vitro activities of the TSHR mutations and the severity
      of hyperthyroidism.

PMID- 20138964
TI  - TGF-beta induces telomerase-dependent pancreatic tumor cell cycle arrest.
AB  - Recent studies suggest that transforming growth factor beta (TGF-beta) inhibits
      telomerase activity by repression of the telomerase reverse transcriptase (TERT)
      gene. In this report, we show that TGF-beta induces TERT repression-dependent
      apoptosis in pancreatic tumor, vascular smooth muscle, and cervical cancer cell
      cultures. TGF-beta activates Smad3 signaling, induces TERT gene repression and
      results in G1/S phase cell cycle arrest and apoptosis. TERT over-expression
      stimulates the G1/S phase transition and alienates TGF-beta-induced cell cycle
      arrest and apoptosis. Our data suggest that telomere maintenance is a limiting
      factor of the transition of the cell cycle. TGF-beta triggers cell cycle arrest
      and death by a mechanism involving telomerase deregulation of telomere
      maintenance.

PMID- 20138966
TI  - Precipitated withdrawal counters the adverse effects of subchronic cannabinoid
      administration on male rat sexual behavior.
AB  - In the present study, sexual behavior of male rats was assessed following
      prolonged treatment with the CB(1) receptor agonist, HU-210 (0.1mg/mg/day for 10
      days) under conditions of drug maintenance, spontaneous withdrawal and
      precipitated withdrawal (induced via administration of the CB(1) receptor
      antagonist AM251; 1mg/kg). Following subchronic cannabinoid treatment, sexual
      activity in male rats was impaired under both the drug maintenance and
      spontaneous withdrawal conditions, as revealed by a reduction in frequency of
      both intromissions and ejaculations. Notably, the induction of precipitated drug
      withdrawal reversed the negative effects of subchronic HU-210 treatment on sexual
      activity as seen by a reversal of the suppression of ejaculations. These data
      illustrate that, contrary to expectations, the impairments in male sexual
      activity following protracted cannabinoid administration are not due to drug
      withdrawal, per se, but are likely mediated by neuroadaptive changes provoked by
      repeated drug exposure.

PMID- 20138965
TI  - Calcium fluxes cause nuclear shrinkage and the translocation of phospholipase C
      delta1 into the nucleus.
AB  - Phospholipase C-delta1 (PLCdelta1) is the most fundamental form of the eukaryotic
      PLC and thought to play important roles in the regulation of cells. We previously
      reported that PLCdelta1 shuttles between the cytoplasm and nucleus, and an influx
      of Ca2+ triggers the nuclear import of PLCdelta1 via Ca2+-dependent interaction
      with importin beta1, although the physiological meaning of this is unclear. Here
      we have examined the distribution of PLCdelta1 using primary cultures of rat
      hippocampal neurons. Treatment of 7DIV neurons with ionomycin or thapsigargin
      caused the nuclear localization of PLCdelta1 as has been observed in other cell
      lines. Similar results were obtained with neurons treated with glutamate,
      suggesting that the nuclear localization of PLCdelta1 plays some roles in
      excitotoxicity associated with ischemic stress. Generally, cells undergoing
      ischemic or hypoxic cell death show nuclear shrinkage. We confirmed that a
      massive influx of Ca2+ caused similar results. Furthermore, overexpression of GFP
      PLCdelta1 facilitated ionomycin-induced nuclear shrinkage in embryonic
      fibroblasts derived from PLCdelta1 gene-knockout mice (PLCdelta1KO-MEF). By
      contrast, an E341A mutant that cannot bind with importin beta1 and be imported
      into the nucleus by ionomycin and also lacks enzymatic activity did not cause
      nuclear shrinkage in PLCdelta1KO-MEF. Nuclear translocation and the PLC activity
      of PLCdelta1, therefore, may regulate the nuclear shape by controlling the
      nuclear scaffold during stress-induced cell death caused by high levels of Ca2+.

PMID- 20138967
TI  - Parallel development of contour integration and visual contrast sensitivity at
      low spatial frequencies.
AB  - It has been suggested that visual contrast sensitivity and contour integration
      functions exhibit a late maturation during adolescence. However, the relationship
      between these functions has not been investigated. The aim of this study was to
      assess the development of visual contrast sensitivity and contour integration in
      152 healthy volunteers aged between 5 and 30 years. The results revealed a
      significant maturation of contrast sensitivity at low spatial frequencies (0.5,
      1.2, and 1.9 cycles/degree) and contour integration. The largest developmental
      step was observed for both contrast sensitivity and contour integration tasks
      when the 5-8-year olds were compared with the 9-11-year olds. There was a
      significant correlation between the development of low spatial frequency contrast
      sensitivity and contour integration. These results raise the possibility that the
      development of low spatial frequency processing may affect attentional
      mechanisms, which may have an impact on early contour integration.

PMID- 20138968
TI  - Protective effect of albumin on VEGF and brain edema in acute ischemia in rats.
AB  - Vascular endothelial growth factor (VEGF) is known to be an important stroke
      related pathogenic factor for the formation of brain edema. We examined the
      therapeutic effect of human serum albumin on VEGF expression in acute ischemic
      stroke. Adult male Sprague-Dawley (SD) rats were subjected to Middle Cerebral
      Artery Occlusion (MCAO), the suture was withdrawn 2 h later, and 25% albumin
      (1.25 g/kg) or saline (5 ml/kg) was administered intravenously after reperfusion.
      The model was evaluated by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining,
      neurological deficits and brain water content. Serum albumin level was
      determined. VEGF expression was studied by enzyme linked immunosorbent assay
      (ELISA), quantitative real-time PCR and immunohistochemistry. We demonstrated
      that albumin administration maintained the serum albumin at a higher level than
      the sham group at 6 h, 1 d, 2 d and 3 d after MCAO, and significantly improved
      the neurological deficits and decreased the brain water content. In addition, the
      strong up-regulation of VEGF expression at 6 h and 1d after MCAO can be
      attenuated by albumin administration. However, albumin administration had no
      significant depressing effect on VEGF expression at 2 d, 3 d and 5 d after MCAO
      in the cortex and hippocampus. Strong up-regulation of VEGF immunoreactivity was
      noted in the saline group in the blood-brain barrier (BBB), and in neurons
      surrounding the peri-infarct area and periventricular area at 24 h after MCAO.
      The expression of VEGF in the albumin group was much weaker. Furthermore, there
      were high correlations between the brain water content with the serum albumin
      level, with serum VEGF protein level, and with brain VEGF mRNA expression at 24 h
      after MCAO. In conclusion, maintaining the serum albumin at a higher level, and
      attenuating endogenous VEGF expression at 6 h and 1d, but not 2 d, 3 d, or 5 d
      after MCAO, may partially contribute to the protective effects of albumin on
      reduction of brain edema in the early stage of ischemia.

PMID- 20138969
TI  - The differential effects of depression on evoked and spontaneous pain behaviors
      in olfactory bulbectomized rats.
AB  - Although it has been accepted that depression and pain are common comorbidities,
      their interaction is not fully understood. The current study was aimed to
      investigate the effects of depression on both evoked pain behavior (thermal
      induced nociception) and spontaneous pain behavior (formalin pain) using an
      olfactory bulbectomy (OB) rat model of depression. Emotional behaviors were
      assessed by open field and Morris water maze tests. The results showed that the
      depressed rats exhibited stronger tolerance to noxious thermal stimulation
      compared to non-depressed animals. In contrast, the spontaneous nociceptive
      behaviors induced by formalin injection were significantly enhanced in the OB
      rats in comparison to control rats. These results demonstrated that depression
      can have differential effects on stimulus-evoked pain and spontaneous pain, with
      alleviation in the former while aggravation in the latter. The present study has
      confirmed our previous findings that depression can inhibit evoked pain but
      facilitate spontaneous pain, and provides evidence that the OB depression model
      is a feasible model for studying the relationship between depression and pain.

PMID- 20138970
TI  - Absence of morphine analgesia and its underlying descending serotonergic
      activation in an experimental mouse model of fibromyalgia.
AB  - Mice exposed to intermittent cold stress (ICS), but not constant cold stress
      (CCS) showed sustained thermal hyperalgesia for up to 12 days. Systemic or
      intracerebroventricular (i.c.v.) injection of morphine caused no significant
      analgesia in ICS mice, but induced dose-dependent analgesia in control mice.
      However, significant analgesic effects were achieved by intrathecal or
      intraplantar injection of morphine. The i.c.v. injection of morphine
      significantly increased the turnover ratio (5-HIAA/5-HT) in the dorsal half of
      the spinal cord of control mice, but not in ICS mice. Collectively, these results
      indicate that the loss of descending serotonergic activation seems to be a key
      mechanism underlying the absence of morphine-induced analgesia.

PMID- 20138971
TI  - Inhibition of NGF-induced neurite outgrowth of rat pheochromocytoma cells (PC12)
      following administration of dioxyamphetamine.
AB  - Amphetamine analogs are known to induce not only neurotoxicity at serotonergic
      axon terminals but also neocortical neuronal degeneration. However, a much less
      studied aspect involves the impact of amphetamine exposure on neuronal
      development. The present study investigated whether pretreatment of PC12 cells
      with dioxyamphetamine (DA) alters differentiation of PC12 cells by NGF and, if
      so, which components of the Ras/Raf/MEK/ERK pathway known to be involved in the
      differentiation response to NGF are particularly affected. Though exposure of
      PC12 cells to DA 1h prior to NGF treatment resulted in apopotosis, several PC12
      cells survived. However, neurite outgrowth of these NGF-responsive cells was
      repressed. Immunoblots of whole cell extracts revealed a strong induction rather
      than inhibition of ERK phosphorylation up to 48h after DA/NGF treatment. Our
      results indicate that NGF-mediated neurite outgrowth was inhibited by
      pretreatment with DA, and this blockage of NGF-induced neuritogenesis was not due
      to an inhibition of ERK phosphorylation.

PMID- 20138972
TI  - A novel bifunctional peptidic aspartic protease inhibitor inhibits chitinase A
      from Serratia marcescens: Kinetic analysis of inhibition and binding affinity.
AB  - BACKGROUND: Chitinase inhibitors have chemotherapeutic potential as fungicides,
      pesticides and antiasthmatics. The majority of chitinase inhibitors reported are
      natural products like argifin, argifin linear fragments, argadin, allosamidin and
      disulfide-cyclized peptides. Here, we report a novel peptidic inhibitor API
      (Aspartic Protease Inhibitor), isolated from Bacillus licheniformis that inhibits
      chitinase A (ChiA) from Serratia marcescens. METHODS: The binding affinity of API
      with ChiA and type of inhibition was determined by the inhibition kinetics
      assays. Fluorescence and CD spectroscopic analysis and chemical modification of
      API with different affinity reagents elucidated the mechanism of binding of API
      with ChiA. RESULTS AND CONCLUSIONS: The peptide has an amino acid sequence N
      Ile(1)-Cys(2)-Glu(3)-Ala(4)-Glu(5)-His(6)-Lys(7)-Trp(8)-Gly(9)-Asp(10)-Tyr(11)
      Leu(12)-Asp(13)-C. The ChiA-API kinetic interactions reveal noncompetitive,
      irreversible and tight binding nature of API with I(50) = 600 nM and K(i)= 510 nM
      in the presence of chromogenic substrate p-nitrophenyl-N,N'-diacetyl-beta
      chitobioside[p-NP-(GlcNAc)(2)]. The inhibition progress curves show a two-step
      slow tight binding inhibition mechanism with the rate constant k(5) = 8.7 +/- 1 x
      10(-3) s(-1) and k(6) = 7.3 +/- 0.6 x 10(-5) s(-1). CD-spectra and tryptophanyl
      fluorescence analysis of ChiA incubated with increasing API concentrations
      confirms conformational changes in enzyme structure which may be due to
      irreversible denaturation of enzyme upon binding of API. Chemical modifications
      by WRK abolished the anti-chitinase activity of API and revealed the involvement
      of carboxyl groups in the enzyme inactivation. Abolished isoindole fluorescence
      of OPTA-labeled ChiA demonstrates the irreversible denaturation of ChiA upon
      incubation with API for prolonged time and distortion of active site of the
      enzyme. GENERAL SIGNIFICANCE: The data provide useful information that could lead
      to the generation of drug-like, natural product-based chitinase inhibitors.

PMID- 20138973
TI  - A cross-laboratory comparison of expression profiling data from normal human
      postmortem brain.
AB  - Expression profiling of post-mortem human brain tissue has been widely used to
      study molecular changes associated with neuropsychiatric diseases as well as
      normal processes such as aging. Changes in expression associated with factors
      such as age, gender or postmortem interval are often more pronounced than changes
      associated with disease. Therefore in addition to being of interest in their own
      right, careful consideration of these effects are important in the interpretation
      of disease studies. We performed a large meta-analysis of genome-wide expression
      studies of normal human cortex to more fully catalogue the effects of age,
      gender, postmortem interval and brain pH, yielding a "meta-signature" of gene
      expression changes for each factor. We validated our results by showing a
      significant overlap with independent gene lists extracted from the literature.
      Importantly, meta-analysis identifies genes which are not significant in any
      individual study. Finally, we show that many schizophrenia candidate genes appear
      in the meta-signatures, reinforcing the idea that studies must be carefully
      controlled for interactions between these factors and disease. In addition to the
      inherent value of the meta-signatures, our results provide critical information
      for future studies of disease effects in the human brain.

PMID- 20138974
TI  - Disturbance of rapid eye movement sleep in senescence-accelerated mouse prone/8
      mice is improved by retinoic acid receptor agonist Am80 (Tamibarotene).
AB  - Senescence-accelerated mouse prone/8 (SAMP8) mice are known to exhibit age
      related deterioration in sleep-wake architecture compared with senescence
      accelerated mouse resistant/1 (SAMR1) mice. We investigated whether treatment
      with Am80 (Tamibarotene), a retinoic acid receptor agonist, would improve sleep
      in 9-10-month-old SAMP8 mice. One week of Am80 administration improved the
      decrease in rapid eye movement (REM) sleep shown by SAMP8 mice. Real-time RT-PCR
      analysis demonstrated an impairment in the hippocampal retinoid cascade (retinoic
      acid receptor alpha and transthyretin) in SAMP8 in comparison to SAMR1 mice. Am80
      treatment induced an increase in mRNA expression in the vesicular acetylcholine
      transporter in the brainstem and transthyretin in the hippocampus. Furthermore,
      decreased cortical acetylcholine content in SAMP8 was improved by Am80
      administration. Decreased non-REM sleep and delta oscillation were also observed
      in SAMP8 mice; however, this was not improved by Am80 administration. These
      results partially support the hypothesis that the effects of aging on sleep-wake
      architecture are improved by the activation of retinoic acid receptors. The
      improvement may be induced by the activation of the cholinergic pathway.

PMID- 20138975
TI  - Do grazing sheep use species-based categorization to select their diet?
AB  - Food item categorization should reduce the cost of information processing by
      herbivores when selecting their diet in complex environments. We assessed the
      ability of sheep to categorize food items by offering them ryegrass (Rg) and
      fescue (Fe) in pots cut tall (T) or short (S). Ewes' preferences were tested in
      three binary choices, RgS-FeT, RgS-FeS and FeT-FeS, before and after aversive
      conditioning against RgT. After conditioning, the ewes decreased their preference
      for RgS, but their choice between tall and short fescue was unchanged. Thus the
      ewes generalized their aversion to the species but not to the sward height.
      Comparing the choices between the two species offered at the same height showed
      choices were similar between RgS and FeS here and between RgT and FeT in Ginane
      and Dumont (2006). We conclude that sheep can use species-based, open-ended
      categorization when selecting their diet, while other plant characteristics, such
      as sward height, are not used to define a category, despite their importance in
      diet selection.

PMID- 20138976
TI  - Spontaneous recovery in human instrumental learning: Integration of information
      and recency to primacy shift.
AB  - This experiment was conducted to study the effect of changes in the retention
      interval (RI) on spontaneous recovery within an acquisition-test interference
      task. College students learned a reversal conditional discrimination to solve a
      task involving conflicting phases across two training phases. When the test was
      conducted immediately after training, participants' performance revealed recency,
      behaving according to the information received during the last phase. Performance
      after retention interval averaged the information received across phases,
      regardless of the length of the RI (1.5, 3, 24 or 48 h). These results are not in
      agreement with traditional theories of spontaneous recovery as they predict a
      recency to primacy shift effect of the RI. An interpretation of spontaneous
      recovery based on a temporal weighting rule (TWR) is discussed.

PMID- 20138977
TI  - The inhibitory effect of hesperidin on tumor cell invasiveness occurs via
      suppression of activator protein 1 and nuclear factor-kappaB in human
      hepatocellular carcinoma cells.
AB  - Hesperidin (HES) has been reported to exhibit anti-invasive and antimetastatic
      activities by suppressing the enzymatic activity of matrix metalloproteinase-9
      (MMP-9). However, the underlying mechanism of anti-invasive activity remains
      unclear so far. First, we suggest that the expression of MMP-9 by TPA involves
      phosphorylation of IKK, p38, and PKC in hepG2. We also demonstrate that
      hesperidin reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell
      invasion and inhibited the secreted and cytosolic MMP-9 forms in HepG2 cells.
      Hesperidin significantly suppressed the TPA-induced the mRNA level of MMP-9.
      Hesperidin suppressed MMP-9 transcription by inhibiting nuclear factor-kappaB (NF
      kappaB) and Activator protein 1 (AP-1) activity. Hesperidin suppressed TPA
      stimulated NF-kappaB translocation into the nucleus through IkappaB inhibitory
      signaling pathways and also inhibited TPA-induced AP-1 activity by the inhibitory
      phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) signaling
      pathways. In conclusion, Hesperidin might be a potent antiinvasive agent that
      suppresses the MMP-9 enzymatic activity via NF-kappaB an AP-1 signaling pathway.

PMID- 20138978
TI  - The eccentricity effect for auditory saccadic reaction times is independent of
      target frequency.
AB  - Although much is understood about the stimulus properties affecting the latency
      of saccadic eye movements to visual targets, relatively little is known about the
      properties affecting saccades to auditory targets. This study examined the effect
      of three primary acoustic features-frequency, intensity, and spatial location-on
      auditory saccade characteristics in humans, and compared them to visual saccades.
      Saccade targets were presented from an azimuthal array of speakers and LEDs
      spanning +/-36 degrees. There was an 'eccentricity effect' for auditory saccades
      such that latencies decreased by up to 70 ms with eccentricity. This was observed
      for all frequencies and intensities tested. There was a smaller effect in the
      opposite direction effect for visual saccades. Auditory saccades had similar
      latencies to visual saccades (within 5 ms) for near midline locations, but were
      up to 90 ms faster at eccentric locations (+/-36 degrees). Overall, saccadic
      latencies were shortest for wideband noise and narrowband noises with center
      frequencies falling within the human speech range. Examination of saccade
      accuracy showed decreasing accuracy with increasing eccentricity, and a negative
      correlation between accuracy and latency for auditory stimuli.

PMID- 20138979
TI  - Reversal of age-associated memory impairment by rosuvastatin in rats.
AB  - Increased levels of iron in brain regions have been reported in neurodegenerative
      disorders as well as in normal brain aging. We have previously demonstrated that
      neonatal iron loading induces cognitive impairment in adult rats. Here, we
      evaluate the effects of neonatal iron treatment on cognition in aged rats. We
      also investigated the effects of a late subchronic rosuvastatin treatment on iron
      and age-induced cognitive deficits. Rats received vehicle or 10.0mg/kg Fe(2+)
      orally at postnatal days 12-14. When animals reached the age of 23 months, they
      received daily intraperitoneal injections of saline or rosuvastatin (0.2 or
      2.0mg/kg) for 21 days. Twenty-four hours after the last injection, they were
      submitted to novel object recognition training. Retention test sessions were
      performed 1.5 and 24h after training, in order to assess short-term and long-term
      memory, respectively. Results indicated that aged animals that received iron in
      the neonatal period showed more severe memory deficits than vehicle-treated ones,
      suggesting that iron potentiates age-associated memory impairments. Rosuvastatin
      improved recognition memory deficits associated with iron loading and aging,
      providing evidence that statins may be considered for the treatment of age
      associated cognitive decline.

PMID- 20138980
TI  - Biocatalytic transformation of nucleoside derivatives.
AB  - Nucleoside derivatives are a class of compounds that have attracted intense
      interest in biotechnology and medicine. Use of biocatalysts opens exciting
      opportunities for selective synthesis of many nucleoside derivatives, and such an
      approach offers simplicity, exquisite selectivity and environmentally benign
      processes. Here we reviewed current achievements in the biocatalytic
      transformation of nucleoside derivatives from the literature between 2000 and
      2009. This article is arranged according to the types of reactions that can be
      employed to transform nucleoside derivatives, which include acylation,
      deacylation, glycosylation, halogenation and deamination.

PMID- 20138981
TI  - Targeted high throughput sequencing of a cancer-related exome subset by specific
      sequence capture with a fully automated microarray platform.
AB  - Sequence capture methods for targeted next generation sequencing promise to
      massively reduce cost of genomics projects compared to untargeted sequencing.
      However, evaluated capture methods specifically dedicated to biologically
      relevant genomic regions are rare. Whole exome capture has been shown to be a
      powerful tool to discover the genetic origin of disease and provides a reduction
      in target size and thus calculative sequencing capacity of >90-fold compared to
      untargeted whole genome sequencing. For further cost reduction, a valuable
      complementing approach is the analysis of smaller, relevant gene subsets but
      involving large cohorts of samples. However, effective adjustment of target sizes
      and sample numbers is hampered by the limited scalability of enrichment systems.
      We report a highly scalable and automated method to capture a 480 Kb exome subset
      of 115 cancer-related genes using microfluidic DNA arrays. The arrays are
      adaptable from 125 Kb to 1 Mb target size and/or one to eight samples without
      barcoding strategies, representing a further 26 - 270-fold reduction of
      calculative sequencing capacity compared to whole exome sequencing. Illumina GAII
      analysis of a HapMap genome enriched for this exome subset revealed a
      completeness of >96%. Uniformity was such that >68% of exons had at least half
      the median depth of coverage. An analysis of reference SNPs revealed a
      sensitivity of up to 93% and a specificity of 98.2% or higher.

PMID- 20138982
TI  - Sickness behavior induced by endotoxin can be mitigated by the dietary soluble
      fiber, pectin, through up-regulation of IL-4 and Th2 polarization.
AB  - Peripheral activation of the immune system by infectious agents triggers the
      brain-cytokine system causing sickness behaviors which profoundly impact well
      being. Dietary fiber is a beneficial foodstuff that, from a gastrointestinal
      tract perspective, exists in both insoluble and soluble forms. We show that a
      diet rich in soluble fiber protects mice from endotoxin-induced sickness behavior
      by polarizing mice Th2 when compared to a diet containing only insoluble fiber.
      Mice fed soluble fiber became less sick and recovered faster from endotoxin
      induced sickness behaviors than mice fed insoluble fiber. In response to
      intraperitoneal endotoxin, mice fed soluble fiber had up-regulated IL-1RA and
      reduced IL-1beta and TNF-alpha in the brain as compared to mice fed insoluble
      fiber. Importantly, mice fed soluble fiber had a basal increase in IL-4 in the
      ileum and spleen which was absent in MyD88 knockout mice. Con-A stimulated
      splenocytes from mice fed soluble fiber showed increased IL-4 and IL-5 and
      decreased IL-2, IL-12 and IFN-gamma when compared to mice fed insoluble fiber.
      Likewise, endotoxin-stimulated macrophages from mice fed soluble fiber
      demonstrated decreased IL-1beta, TNF-alpha, IFN-gamma, IL-12 and nitrate and
      increased IL-1RA, arginase 1 and Ym1 when compared to mice fed insoluble fiber.
      Finally, the behavioral protection afforded by feeding mice soluble fiber was
      reduced in IL-4 knockout mice, as was the impact of soluble fiber on Con-A
      stimulated splenocytes and endotoxin activated macrophages. These data show that
      a diet rich in soluble fiber protects against endotoxin-induced sickness behavior
      by polarizing mice Th2 and promoting alternative activation of macrophages.

PMID- 20138983
TI  - Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during
      the course of experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple
      sclerosis, where disease is mediated by autoantigen-specific T cells. Although
      there is evidence linking CD4(+) T cells that secrete IL-17, termed Th17 cells,
      and IFN-gamma-secreting Th1 cells with the pathogenesis of EAE, the precise
      contribution of these T cell subtypes or their associated cytokines is still
      unclear. We have investigated the infiltration of CD4(+) T cells that secrete IFN
      gamma, IL-17 or both cytokines into CNS during development of EAE and have
      examined the role of T cells in microglial activation. Our findings demonstrate
      that Th17 cells and CD4(+) T cells that produce both IFN-gamma and IL-17, which
      we have called Th1/Th17 cells, infiltrate the brain prior to the development of
      clinical symptoms of EAE and that this coincides with activation of CD11b(+)
      microglia and local production of IL-1beta, TNF-alpha and IL-6 in the CNS. In
      contrast, significant infiltration of Th1 cells was only detected after the
      development of clinical disease. Co-culture experiments, using mixed glia and MOG
      specific T cells, revealed that T cells that secreted IFN-gamma and IL-17 were
      potent activators of pro-inflammatory cytokines but T cells that secrete IFN
      gamma, but not IL-17, were less effective. In contrast both Th1 and Th1/Th17
      cells enhanced MHC-class II and co-stimulatory molecule expression on microglia.
      Our findings suggest that T cells which secrete IL-17 or IL-17 and IFN-gamma
      infiltrate the CNS prior to the onset of clinical symptoms of EAE, where they may
      mediate CNS inflammation, in part, through microglial activation.

PMID- 20138984
TI  - Development of TaqMan allelic specific discrimination assay for detection of the
      most common Sardinian Wilson's disease mutations. Implications for genetic
      screening.
AB  - Wilson's disease (WD) is an autosomal recessive disorder caused by a defective
      function of the copper transporting ATP7B protein. Analysis of ATP7B gene in the
      Sardinian population revealed the presence of six common mutations that together
      account for 85% of WD chromosomes. We have developed an automated approach for
      the detection of these 6 common Sardinian mutations based on TaqMan technology.
      Ten DNA samples of WD patients carrying different combinations of the six most
      common Sardinian mutations and normal controls previously analysed were used in
      triplicate to set up the allelic discrimination assays. The system was validated
      in 96 samples obtained from WD patients carrying different combinations of the
      most common mutations under investigation. The results showed that allelic
      discrimination is a valid method that could be used for efficient diagnosis of
      single cases but also for a mass screening.

PMID- 20138985
TI  - Phosphorylation of PRAS40 on Thr246 by PKB/AKT facilitates efficient
      phosphorylation of Ser183 by mTORC1.
AB  - Type 2 diabetes is associated with alterations in protein kinase B (PKB/Akt) and
      mammalian target of rapamycin complex 1 (mTORC1) signalling. The proline-rich Akt
      substrate of 40-kDa (PRAS40) is a component of mTORC1, which has a regulatory
      function at the intersection of the PKB/Akt and mTORC1 signalling pathway.
      Phosphorylation of PRAS40-Thr246 by PKB/Akt, and PRAS40-Ser183 and PRAS40-Ser221
      by mTORC1 results in dissociation from mTORC1, and its binding to 14-3-3
      proteins. Although all phosphorylation sites within PRAS40 have been implicated
      in 14-3-3 binding, substitution of Thr246 by Ala alone is sufficient to abolish
      14-3-3 binding under conditions of intact mTORC1 signalling. This suggests that
      phosphorylation of PRAS40-Thr246 may facilitate efficient phosphorylation of
      PRAS40 on its mTORC1-dependent sites. In the present study, we investigated the
      mechanism of PRAS40-Ser183 phosphorylation in response to insulin. Insulin
      promoted PRAS40-Ser183 phosphorylation after a euglycaemic-hyperinsulinaemic
      clamp in human skeletal muscle. The insulin-induced PRAS40-Ser183 phosphorylation
      was further evidenced in vivo in rat skeletal and cardiac muscle, and in vitro in
      A14 fibroblasts, 3T3L1 adipocytes and L6 myotubes. Inhibition of mTORC1 by
      rapamycin or amino acid deprivation partially abrogated insulin-mediated PRAS40
      Ser183 phosphorylation in cultured cell lines. However, lowering insulin-induced
      PRAS40-Thr246 phosphorylation using wortmannin or palmitate in cell lines, or by
      feeding rats a high-fat diet, completely abolished insulin-mediated PRAS40-Ser183
      phosphorylation. In addition, replacement of Thr246 by Ala reduced insulin
      mediated PRAS40-Ser183 phosphorylation. We conclude that PRAS40-Ser183 is a
      component of insulin action, and that efficient phosphorylation of PRAS40-Ser183
      by mTORC1 requires the phosphorylation of PRAS40-Thr246 by PKB/Akt.

PMID- 20138986
TI  - Erk 5 is necessary for sustained PDGF-induced Akt phosphorylation and inhibition
      of apoptosis.
AB  - Extracellular regulated kinase (Erk) 5 is a member of the mitogen activated
      protein (MAP) kinase family that has been implicated in both cell proliferation
      and survival. In the present study, we found that stimulation with platelet
      derived growth factor (PDGF)-BB leads to a transient activation of Erk5, which
      was shown to be dependent on recruitment of both Src kinases and the tyrosine
      phosphatase Shp2 to the activated PDGF receptor beta (PDGFRbeta). We could also
      demonstrate that Shp2 docking to the receptor is critical for Src kinase
      activation, suggesting that Shp2 may contribute to Erk5 activation through its
      involvement in Src kinase activation. Under control conditions, PDGF-BB promoted
      a sustained Akt phosphorylation. However, reduction of the expression of Erk5 by
      siRNA resulted in only a transient Akt phosphorylation, and an inability of PDGF
      BB to suppress caspase 3 activation and inhibit apoptotic nuclear morphological
      changes such as condensed or fragmented chromatin under serum-free conditions.

PMID- 20138987
TI  - Vav1 couples the T cell receptor to cAMP response element activation via a PKC
      dependent pathway.
AB  - The transcription factor cAMP-responsive element binding protein (CREB) is a
      regulator of the expression of several genes important for lymphocyte activation
      and proliferation. However, the proximal signaling events leading to activation
      of CREB in T cells upon antigen receptor stimulation remain unknown. Here we
      identify a role for Vav1 in the activation of the cAMP response element (CRE),
      the binding site for CREB. T cell receptor (TCR)/CD28 - induced costimulation of
      Jurkat T cells expressing Vav1 but not a GEF-deficient mutant showed increased
      CRE activation (7.2+/-2.4 fold over control), whereas Vav1 downregulation by
      siRNA reduced activation of CRE by 2.6+/-1.3 fold. Inhibition of PKC and MEK but
      not p38 could reduce Vav1-mediated CRE activation, suggesting that Vav1 transmits
      TCR and CD28 signals to activation of CRE via PKC and ERK signaling pathways. As
      a consequence, downregulation of Vav1 impaired the expression of several CRE
      containing genes like cyclin D1, INFgamma and IL-2, whereas overexpression of
      Vav1 enhanced CRE-dependent gene expression. Furthermore, cAMP-induced CRE
      dependent transcription and gene expression was also modulated by Vav1, but did
      not require activation of PKC and the GEF function of Vav1. Our data provide
      insights into the signal transduction events regulating CRE-mediated gene
      expression in T cells, which affects T cell development, proliferation and
      activation. We identify Vav1 as an essential component of TCR-induced CRE
      activation and gene expression, which underlines the central role for Vav1 as key
      player for TCR signal transduction and gene expression.

PMID- 20138988
TI  - The scientific legacy of Jacques Monod.
AB  - The operon model was the last "great" discovery of molecular biology, and a
      decisive event for the entrance of molecular biology into embryology. But the
      work of Monod was not limited to the elaboration of this model. He was one of the
      founders of molecular biology, in the paradigm of which biologists still work. I
      focus on two episodes of Monod's career--his strong opposition to Lysenkoism and
      the elaboration of the allosteric model--to outline the ideas and convictions of
      the early molecular biologists.

PMID- 20138989
TI  - Heat shock protein 90 interacts with vitamin D receptor in human leukemia cells.
AB  - The active form of vitamin D, 1alpha,25-dihydroxyvitamin D3 (1,25D), has a broad
      range of effects which are mediated by nuclear vitamin D receptor (VDR). Many
      experiments that investigate the role of VDR can be done in human acute myeloid
      leukemia (AML) cells, since these cells are responsive to 1,25D and express VDR
      in a 1,25D-regulated manner. In this paper we show that in HL60 and in THP-1
      cells VDR protein interacts with heat shock protein 90 (Hsp90) and that Hsp90 is
      important for differentiation of AML cells. Geldanamycin (GA), an Hsp90
      inhibitor, is able to suppress 1,25-induced differentiation of HL60 cells.

PMID- 20138990
TI  - The transcription factors Snail1 and Snail2 repress vitamin D receptor during
      colon cancer progression.
AB  - Vitamin D receptor (VDR) mediates the antitumoral action of the active vitamin D
      metabolite 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). However, VDR expression
      is lost during colon cancer progression, possibly causing unresponsiveness to
      1,25(OH)2D3. Although several mechanisms responsible for resistance to
      1,25(OH)2D3 action in different types of cancer had been reported, none explained
      the loss of VDR expression. We have found that the transcription factors Snail1
      and Snail2, known as inducers of epithelial-to-mesenchymal transition (EMT),
      inhibit VDR expression and block 1,25(OH)2D3 action in colon cancer cells. Snail1
      and Snail2 have an additive repressing effect on VDR gene promoter. These effects
      are specific to the Snail family, as other transcription factors that function as
      EMT inducers do not inhibit VDR expression in colon cancer cells. Moreover, we
      also found that the RNA expression of SNAI1 and SNAI2 is upregulated in human
      colorectal tumors and inversely correlates with that of VDR. Our results suggest
      that high levels of SNAIL1 and SNAIL2 are a probable cause of VDR downregulation
      and 1,25(OH)2D3 unresponsiveness in colon cancer. In addition, they may
      contribute to the improvement of protocols for the clinical use of vitamin D
      compounds, as they indicate that advanced colon cancer patients overexpressing
      SNAIL1 and SNAIL2 are not suitable candidates for this therapy.

PMID- 20138991
TI  - The vitamin D receptor, the skin and stem cells.
AB  - The active metabolite of vitamin D, 1,25-dihydroxyvitamin D, has been shown to
      have pro-differentiation and antiproliferative effects on keratinocytes that are
      mediated by interactions with its nuclear receptor. Other cutaneous actions of
      the vitamin D receptor have been brought to light by the cutaneous phenotype of
      humans and mice with non-functional vitamin D receptors. Although mice lacking
      functional vitamin D receptors develop a normal first coat of hair, they exhibit
      impaired cyclic regeneration of hair follicles that leads to the development of
      alopecia. Normal hair cycling involves reciprocal interactions between the dermal
      papilla and the epidermal keratinocyte. Studies in mice with targeted ablation of
      the vitamin D receptor demonstrate that the abnormality in the hair cycle is due
      to a defect in the keratinocyte component of the hair follicle. Furthermore,
      expression of mutant vitamin D receptor transgenes in the keratinocytes of
      vitamin D receptor knockout mice demonstrates that the effects of the receptor
      that maintain hair follicle homeostasis are ligand-independent. Absence of a
      functional vitamin D receptor leads to impaired function of keratinocyte stem
      cells, both in vivo and in vitro. This is manifested by impaired cyclic
      regeneration of the hair follicle, a decrease in bulge keratinocyte stem cells
      with ageing and an abnormality in lineage progression of these cells, leading to
      their preferential differentiation into sebocytes.

PMID- 20138992
TI  - Deep brain stimulation changes basal ganglia output nuclei firing pattern in the
      dystonic hamster.
AB  - Dystonia is a heterogeneous syndrome of movement disorders characterized by
      involuntary muscle contractions leading to abnormal movements and postures. While
      medical treatment is often ineffective, deep brain stimulation (DBS) of the
      internal pallidum improves dystonia. Here, we studied the impact of DBS in the
      entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus
      internus, on basal ganglia output in the dt(sz)-hamster, a well-characterized
      model of dystonia by extracellular recordings. Previous work has shown that EP
      DBS improves dystonic symptoms in dt(sz)-hamsters. We report that EP-DBS changes
      firing pattern in the EP, most neurons switching to a less regular firing pattern
      during DBS. In contrast, EP-DBS did not change the average firing rate of EP
      neurons. EP neurons display multiphasic responses to each stimulation impulse,
      likely underlying the disruption of their firing rhythm. Finally, neurons in the
      substantia nigra pars reticulata display similar responses to EP-DBS, supporting
      the idea that EP-DBS affects basal ganglia output activity through the activation
      of common afferent fibers.

PMID- 20138993
TI  - The intricate involvement of the Insulin-like growth factor receptor signaling in
      mild traumatic brain injury in mice.
AB  - Insulin-like growth factor-1 (IGF-1) was suggested as a potential neuroprotective
      treatment for traumatic brain injury (TBI) induced damage (cognitive as well as
      cellular). The main goal of the present study was to evaluate the role of the IGF
      1R activation in spatial memory outcome following mild traumatic brain injury.
      mTBI-induced phosphorylation of IGF-1R, AKT and ERK1/2, in mice hippocampus,
      which was inhibited when mice were pretreated with the selective IGF-1R inhibitor
      AG1024. IGF-1 administration prevented spatial memory deficits following mTBI.
      Surprisingly, blocking the IGF-1R signaling in mTBI mice did not augment the
      spatial memory deficit. In addition, this data imply an intriguing and complex
      role of the IGF-1 signaling axis in the cellular and behavioral events following
      mTBI.

PMID- 20138994
TI  - Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in a
      mutant mouse model of Rett syndrome.
AB  - Motor and cognitive functions are severely impaired in Rett syndrome (RTT). Here,
      we examined local synaptic circuits of layer 2/3 (L2/3) pyramidal neurons in
      motor-frontal cortex of male hemizygous MeCP2-null mice at 3 to 4weeks of age. We
      mapped local excitatory input to L2/3 neurons using glutamate uncaging and laser
      scanning photostimulation, and compared synaptic input maps recorded from MeCP2
      null and wild type (WT) mice. Local excitatory input was significantly reduced in
      the mutants. The strongest phenotype was observed for lateral (horizontal,
      intralaminar) inputs, that is, L2/3-->2/3 inputs, which showed a large reduction
      in MeCP2(-/y) animals. Neither the amount of local inhibitory input to these L2/3
      pyramidal neurons nor their intrinsic electrophysiological properties differed by
      genotype. Our findings provide further evidence that excitatory networks are
      selectively reduced in RTT. We discuss our findings in the context of recently
      published parallel studies using selective MeCP2 knockdown in individual L2/3
      neurons.

PMID- 20138995
TI  - The GABA B receptor antagonists CGP35348 and CGP52432 inhibit glycine exocytosis:
      study with GABA B1- and GABA B2-deficient mice.
AB  - GABA(B) receptors mediate inhibition of neurotransmitter exocytosis from nerve
      endings. Unexpectedly, the well known GABA(B) receptor antagonist CGP35348 and,
      in part, the compound CGP52432, are now found to inhibit on their own the K(+)
      evoked exocytosis of glycine when added at low micromolar concentrations to
      superfused mouse glycinergic nerve endings prelabelled with [(3)H]glycine through
      GLYT2 transporters. CGP35348 inhibited [(3)H]glycine release both in spinal cord
      and in hippocampus, but was also able to prevent the inhibitory effect of (-)
      baclofen; CGP52432 exhibited intrinsic activity only in the hippocampus; in
      spinal cord, it behaved exclusively as a silent orthosteric antagonist by
      blocking the release inhibition brought about by (-)-baclofen. The intrinsic
      activity of CGP35348 in spinal cord was not prevented by CGP52432, indicating
      that CGP35348 is not a partial GABA(B) agonist in this experimental system.
      CGP54626, an extremely potent antagonist, exhibited only a minimal intrinsic
      activity. SCH50911, a GABA(B) antagonist belonging to a different chemical class,
      was devoid of significant activity, while phaclofen was effective only at 100-300
      microM. In synaptosomes purified from the spinal cord or the hippocampus of mice
      lacking either the GABA(B1) (GABA(B1-/-) mice) or the GABA(B2) (GABA(B2-/-) mice)
      subunit, the evoked exocytosis of [(3)H]glycine was no longer inhibited by (-)
      baclofen, whereas the intrinsic activity of CGP35348 and CGP52432 was not
      decreased. Activation of unknown sites on glycinergic terminals is likely to be
      involved. These unexpected effects should not be ignored when interpreting
      results obtained with the above GABA(B) receptor antagonists.

PMID- 20138996
TI  - Pharmacological manipulations of CNS sirtuins: potential effects on metabolic
      homeostasis.
AB  - Sirtuins are deacetylases and/or mono-ADP-ribosyltransferases found in organisms
      ranging from bacteria to humans. These enzymes use oxidized nicotinamide adenine
      dinucleotide (NAD(+)) and a long array of different proteins (e.g.: histones,
      transcription factors, cofactors, members of the electron transport chain, etc.)
      as substrates. Sirtuins-mediated reactions yield deacetylated proteins,
      nicotinamide (NAM) and 2'-O-acetyl-ADP-ribose (O-AADPr) or mono-ADP-ribosylated
      proteins and NAM. As these post-translational modifications change the activity
      of their targets and sirtuins depend on NAD(+) to function, these enzymes are
      thought to link metabolic statuses with cellular gene expression, activity and
      fate; as such sirtuins are thought to be bona fide metabolic-sensor proteins. Due
      to their diverse targets, sirtuins affect metabolism, senescence, longevity,
      circadian rhythms and many other biological and physiological programs. In this
      review we focus on their known roles on metabolic homeostasis with particular
      emphasis on their functions in neurons within the central nervous system (CNS).
      We also touch upon the possible metabolic outcomes of pharmacological
      manipulations of CNS sirtuins.

PMID- 20138997
TI  - The dual fatty acid amide hydrolase/TRPV1 blocker, N-arachidonoyl-serotonin,
      relieves carrageenan-induced inflammation and hyperalgesia in mice.
AB  - Given that the pharmacological or genetic inactivation of fatty acid amide
      hydrolase (FAAH) counteracts pain and inflammation, and on the basis of the
      established involvement of transient receptor potential vanilloid type-1 (TRPV1)
      channels in inflammatory pain, we tested the capability of a dual FAAH/TRPV1
      blocker, N-arachidonoyl-serotonin (AA-5-HT), to relieve oedema and pain in a
      model of acute inflammation, and compared its efficacy with that of a single FAAH
      inhibitor (URB597) or TRPV1 antagonist (capsazepine). Acute inflammation was
      induced by intraplantar injection of lambda-carrageenan into mice and the anti
      inflammatory and anti-nociceptive actions of AA-5-HT were assessed at different
      doses, time points and treatment schedule. In addition, endocannabinoid levels
      were measured in paw skin and spinal cord. Systemic administration of AA-5-HT
      elicited dose-dependent anti-oedemigen and anti-nociceptive effects, whereas it
      was devoid of efficacy when given locally. When tested in a therapeutic regimen,
      the compound retained comparable anti-inflammatory effects. TRPV1 receptor
      mediated the anti-inflammatory property of AA-5-HT, whereas both CB(1) and TRPV1
      receptors were involved in its anti-hyperalgesic activity. These effects were
      accompanied by an increase of the levels of the endocannabinoid anandamide (AEA)
      in both inflamed paw and spinal cord. AA-5-HT was more potent than capsazepine as
      anti-oedemigen and anti-hyperalgesic drug, whereas it shows an anti-oedemigen
      property similar to URB597, which was, however, devoid of the anti-nociceptive
      effect. AA-5-HT did not induce unwanted effects on locomotion and body
      temperature. In conclusion AA-5-HT has both anti-inflammatory and anti
      hyperalgesic properties and its employment offers advantages, in terms of
      efficacy and lack of adverse effects, deriving from its dual activity.

PMID- 20138998
TI  - Bias in the Cq value observed with hydrolysis probe based quantitative PCR can be
      corrected with the estimated PCR efficiency value.
AB  - For real-time monitoring of PCR amplification of DNA, quantitative PCR (qPCR)
      assays use various fluorescent reporters. DNA binding molecules and hybridization
      reporters (primers and probes) only fluoresce when bound to DNA and result in the
      non-cumulative increase in observed fluorescence. Hydrolysis reporters (TaqMan
      probes and QZyme primers) become fluorescent during DNA elongation and the
      released fluorophore remains fluorescent during further cycles; this results in a
      cumulative increase in observed fluorescence. Although the quantification
      threshold is reached at a lower number of cycles when fluorescence accumulates,
      in qPCR analysis no distinction is made between the two types of data sets.
      Mathematical modeling shows that ignoring the cumulative nature of the data
      leaves the estimated PCR efficiency practically unaffected but will lead to at
      least one cycle underestimation of the quantification cycle (C(q) value),
      corresponding to a 2-fold overestimation of target quantity. The effect on the
      target-reference ratio depends on the PCR efficiency of the target and reference
      amplicons. The leftward shift of the C(q) value is dependent on the PCR
      efficiency and with sufficiently large C(q) values, this shift is constant. This
      allows the C(q) to be corrected and unbiased target quantities to be obtained.

PMID- 20138999
TI  - Using oocyte nuclei for studies on chromatin structure and gene expression.
AB  - The giant nucleus of amphibian oocytes is generally referred to as the germinal
      vesicle (GV). Its size allows relatively easy manual isolation from the rest of
      the oocyte and also presents a large target in situ for microinjection of
      macromolecules including plasmid DNA, RNA species, antibodies and other proteins
      and even whole organelles, including somatic cell nuclei. Thus the use of GVs is
      excellent for two major types of study: the function of endogenous nuclear
      processes such as gene transcription, RNA processing and intra-nuclear dynamics;
      and the use of the nuclear components to effect processes such as chromatin
      assembly, expression of foreign genes and nucleocytoplasmic transport of injected
      biomolecules. This article outlines some basic techniques appropriate for GV
      studies, particularly the preparation of oocytes for microinjection and the
      isolation of germinal vesicles into an oil phase. As an aid to the targeting of
      the GV within the nucleus, descriptions are given of the use of oocytes from
      albino animals.

PMID- 20139000
TI  - Measuring the conformational space of square four-helical bundles with the
      program samCC.
AB  - Four-helical bundles are the most abundant topological motif among helical folds.
      Their constituent helices show crossing angles that mainly cluster around +20
      degrees (aligned) or -50 degrees (orthogonal). Bundles with all helices aligned
      are called 'square' and comprise four-helical coiled coils as their structurally
      most regular form. Since coiled coils can be described fully by parametric
      equations, they can serve as a reference point for quantifying the conformational
      space of all square bundles. To this end we have developed a program, samCC,
      which measures the deviation of a given bundle from an idealized coiled coil and
      decomposes this into axial rotation and axial, radial, and angular shifts. We
      present examples of analyses performed with the program and focus in particular
      on the axial rotation states of helices in coiled coils, in order to gain further
      insight into a proposed mechanism for transmembrane signal transduction, which
      involves a 26 degrees axial rotation of helices between a canonical coiled coil
      and a variant called the Alacoil. We find that, unlike expected from the
      mechanistic model, coiled coils show a continuum of axial rotation states,
      suggesting that the Alacoil does not represent a single, defined state. We also
      find that one of the originally proposed Alacoil proteins, Rop, in fact has
      canonical packing. SamCC is freely available as a web service
      athttp://toolkit.tuebingen.mpg.de/samcc.

PMID- 20139001
TI  - Specific coiled-coil interactions contribute to a global model of the structure
      of the spindle pole body.
AB  - As the microtubule-organizing center of yeast, the spindle pole body (SPB) is
      essential for cell viability. Structural studies of the SPB are limited by its
      low copy number in the cell, its large size and heterogeneous composition, and
      its association with the nuclear membrane. However, low-resolution or indirect
      structural information about the SPB may be deciphered through a variety of
      techniques. Interestingly, a large proportion of SPB proteins are predicted to
      contain one or more coiled coils, a common protein interaction motif. The high
      frequency of coiled coils suggests that this structure is important for
      establishing the overall architecture of the complex. Support for this hypothesis
      was reported previously for coiled coils from some SPB proteins. Here, we extend
      this approach of isolating and characterizing additional SPB coiled coils to
      improve our understanding of SPB structure and organization. Self-associating
      coiled coils from Bbp1, Mps2, and Nbp1 were observed to form stable parallel
      homodimers in solution. Coiled-coil peptides from Bbp1 and Mps2 were also
      observed to hetero-associate. Experimental coiled-coil interaction data from this
      work and previous studies, as well as predicted and experimental structures for
      other SPB protein fragments and domains, were integrated to generate a model of
      the SPB structure.

PMID- 20139002
TI  - Molecular cloning, expression and antioxidant activity of a peroxiredoxin 2
      homologue from Lampetra japonica.
AB  - Peroxiredoxin (Prx) is a cellular antioxidant protein family that plays important
      roles in oxidative stress and immune cytotoxicity. In this study, we cloned a
      homologue of the Prx2 from the buccal gland of Lampetra japonica (L. japonica).
      L. japonica Prx2 (Lj-Prx2) contained two highly conserved motifs and shared more
      than 70% identity with the homologs from other vertebrate species. Phylogenetic
      analysis revealed that Lj-Prx2 is closely related to other available teleost
      Prx2. The real-time PCR results demonstrated that the Prx2 gene was widely
      expressed in adult lamprey. In addition, the expression of Prx2 gene was
      particularly up-regulated in red blood cells (RBCs) after the experimental
      animals were challenged with lipopolysaccharide (LPS) in vivo. Lj-Prx2 gene was
      subcloned into the pET23b vector and expressed in Escherichia coli BL21 (DE3).
      The recombinant L. japonica Prx2 (rLj-Prx2) was purified by using His Bind
      affinity chromatography. Polyclonal antibody to rLj-Prx2 was generated in New
      Zealand Rabbit. Western blot analysis showed that the Lj-Prx2 is present in the
      buccal gland secretion, suggesting the secretory feature of it. The function
      assays revealed that rLj-Prx2 has the capability to reduce the H2O2 when
      dithiothreitol (DTT) is used as a reducing equivalent and to protect DNA from
      oxidative damage. These findings suggested that Lj-Prx2 probably plays an
      essential role in antioxidant defense in RBCs to keep lamprey alive.

PMID- 20139003
TI  - Immunomodulatory effect of dietary Saccharomyces cerevisiae, beta-glucan and
      laminaran in mercuric chloride treated Nile tilapia (Oreochromis niloticus) and
      experimentally infected with Aeromonas hydrophila.
AB  - Six hundred and forty Nile tilapia (Oreochromis niloticus) weighing 80-100g were
      randomly allocated into eight equal groups (80 each). The first group acts as
      control. Groups S, B and L were fed on a ration supplemented with Saccharomyces
      cerevisiae, beta-glucans and laminaran, respectively for 21 days. Groups M, MS,
      MB and ML were subjected throughout the experiment to sublethal concentration of
      mercuric chloride (0.05 ppm). Gps. MS, MB and ML were fed on a ration containing
      S. cerevisiae, beta-glucan and laminaran respectively for 21 days. Fish were
      challenged with Aeromonas hydrophila (0.4 x 10(7) cells mL(-1)) via intra
      peritoneal injection and the mortality rate was recorded up to 10 day post
      challenge. The non-specific defense mechanisms, cellular and humoral immunity,
      beside the total and differential leukocytic count were determined. Lymphocyte
      transformation index, phagocytic activity percent, phagocytic index, total
      lymphocyte count, serum bactericidal activity and nitric oxide as well as the
      survival rate were insignificantly changed after 21 day in gps. MS&ML, when
      compared with mercuric chloride immune depressed group M. These parameters as
      well as the neutrophil adhesion, serum nitric oxide and survival rate were
      significantly increased in gp. MB when compared with gp. M. Meanwhile the
      cellular and humoral immunity beside the survival rate were significantly
      increased in groups S, B, L when compared with control group. It could be
      concluded that the whole yeast S. cerevisiae, beta-glucan and laminaran can be
      used as immunostimulants for the farmed Nile tilapia. The beta-glucans could be
      used in farmed Nile tilapia, under immune depressive stressful condition to
      increase their resistance to diseases.

PMID- 20139004
TI  - The Zalpha domain of PKZ from Carassius auratus can bind to d(GC)(n) in negative
      supercoils.
AB  - PKZ was the most recently discovered member of eIF2alpha kinase family in fish.
      CaPKZ, the first identified fish PKZ, possessed a conserved eIF2alpha kinase
      catalytic domain in C-terminal and two Z-DNA binding domains (Zalpha) in N
      terminal. The Zalpha of CaPKZ closely resembled that of other Z-DNA binding
      proteins: ADAR1, DLM-1, and E3L. In order to understand more about the function
      of CaPKZ, we expressed and purified three constructed peptides of CaPKZ
      (P(Zalpha)): P(Zalpha1Zalpha2), P(Zalpha1Zalpha1) and P(Zalpha2)(Zalpha2).
      Moreover, most of the plasmids containing d(GC)(n) inserts were maintained in the
      Z-conformation, as confirmed by using inhibition of methylation experiments and
      anti-Z-DNA antibody. Gel mobility shift assays were then used to examine the
      affinity of these P(Zalpha) to the recombinant plasmids. Meanwhile, a competition
      experiment using P(Zalpha1Zalpha2) and anti-Z-DNA antibody was performed. The
      results revealed that P(Zalpha1Zalpha2) and P(Zalpha1Zalpha1) were able to bind
      to the recombinant plasmids with high affinity, whereas P(Zalpha2)(Zalpha2) could
      not bind to it. In addition, dimerization of P(Zalpha1Zalpha2) indicated the
      function unit of Zalpha of CaPKZ would be a dimer.

PMID- 20139005
TI  - Characterization of the flounder IL-6 promoter and its regulation by the p65 NF
      kappaB subunit.
AB  - Interleukin (IL)-6 plays important roles in the regulation of the immune response
      and inflammation in many cell types and its induction by bacterial endotoxins or
      cytokines is regulated at the transcriptional level. The present study
      demonstrates the isolation and characterization of the flounder IL-6 promoter
      sequence and its transcriptional regulation in olive flounder (hirame) natural
      embryo (HINAE) cells. The promoter region (-400 to +79 bp from the transcription
      initiation site) of the flounder IL-6 gene contains putative cis-regulatory
      elements for CCAAT-enhancer-binding proteins (C/EBP; -346 to -355 bp and -166 to 
      160 bp), cAMP response element binding (CREB; -81 to -85 bp), the activator
      protein 1 (AP-1; -56 to -62 bp), and NF-kappaB (-39 to -48 bp). Transfection of
      p65 stimulated the PoIL-6-luc-WT reporter, but not the PoIL-6-luc-kappaB mt
      reporter, and treatment with LPS augmented p65-stimulated reporter activity in
      HINAE cells. In contrast, transfection of C/EBPbeta or c-Jun failed to induce
      synergistic effects in the LPS-driven PoIL-6-luc-WT reporter activity. These
      results give us new insight into the regulation of flounder IL-6 transcription by
      the p65 NF-kappaB subunit.

PMID- 20139006
TI  - Effects of the probiotic, Bacillus subtilis E20, on the survival, development,
      stress tolerance, and immune status of white shrimp, Litopenaeus vannamei larvae.
AB  - In this study, the probiotic, Bacillus subtilis E20, isolated from the human
      health food, natto, was used for white shrimp, Litopenaeus vannamei, larvae
      breeding to improve the larval survival rate and development by adding probiotic
      to the rearing water at (control), 10(8), and 10(9) cfu L(-1) salt water once
      every 3 days during the 14 days of breeding experiment. Thereafter, stress
      tolerance and immune status of postlarvae were evaluated. Shrimp larval
      development was significantly accelerated after adding the probiotic to the
      larval rearing water at a level of 10(9) cfu L(-1). The survival rate of larvae
      was significantly higher in the treatment with 10(9) cfu L(-1) compared to the
      control and the treatment with 10(8) cfu L(-1) after all larvae had metamorphosed
      to postlarvae. Adding the probiotic to the shrimp larvae rearing water produced a
      weak inhibition of bacterial growth by an analysis of the total bacterial count
      and presumptive Vibrio count. For stress tests, no postlarvae died when they were
      reared in water in which the temperature was decreased from 30 to 2 degrees C at
      a rate of 0.1 degrees C min(-1). Postlarvae had significantly lower cumulate
      mortality in the treatments with 10(8) and 10(9) cfu L(-1) compared to the
      control when they were suddenly exposed to fresh water and 60 per thousand salt
      water. A significant decrease in the cumulative mortality of postlarvae treated
      with the probiotic at a level of 10(9) cfu L(-1) was recorded after the sudden
      transfer to 300 mg L(-1) nitrite-N compared to the control and treatment with
      10(8) cfu L(-1). The analysis of immune-related gene expressions showed that the
      gene expression of prophenoloxidase I, prophenoloxidase II, and lysozyme of
      larvae were significantly increased after being reared in probiotic-containing
      water at the levels of 10(8) and 10(9) cfu L(-1). However, no significant
      difference in serine proteinase or glutathione peroxidase gene expressions was
      recorded in this study. It is therefore suggested that 10(9) cfu L(-1) of
      probiotic, B. subtilis E20 adding to rearing water for shrimp larva breeding.

PMID- 20139007
TI  - Administration of the hot-water extract of Spirulina platensis enhanced the
      immune response of white shrimp Litopenaeus vannamei and its resistance against
      Vibrio alginolyticus.
AB  - White shrimp Litopenaeus vannamei which had been injected with the hot-water
      extract of Spirulina platensis at 6, 10, and 20 microg g(-1), or immersed in
      aerated seawater containing extract at 200, 400, and 600 mg L(-1) were challenged
      with Vibrio alginolyticus at 1.5 x 10(6) or 1.4 x 10(6) colony-forming units
      (cfu) shrimp(-1), and then placed in seawater. Survival rates of shrimp that
      received the extract of S. platensis at 6-20 microg g(-1), and those of shrimp
      immersed in seawater containing the extract at 400 and 600 mg L(-1) were
      significantly higher than those of control shrimp after 24-96 and 48-96 h,
      respectively. In a separate experiment, the hyaline cell (HC) count, granular
      cell (GC, including semi-granular cell) count, total haemocyte count (THC),
      phenoloxidase (PO) activity, respiratory burst (RB), superoxide dismutase (SOD)
      activity, glutathione peroxidase (GPx) activity, and lysozyme activity were
      measured when shrimp were injected with the extract at 6, 10, and 20 microg g(
      1), and immersed in seawater containing the extract at 200, 400, and 600 mg L(
      1). These parameters directly increased with the concentration, and significantly
      increased when shrimp were immersed in the seawater containing the extract at 0.5
      4 h. L. vannamei that received all doses of the extract via injection or via
      immersion all had increased phagocytic activity and clearance efficiency to V.
      alginolyticus at 12-72 h and 3-4 h, respectively. It was concluded that L.
      vannamei that received the hot-water extract of S. platensis had enhanced innate
      immunity and increased resistance against V. alginolyticus infection.

PMID- 20139008
TI  - Effects of dietary beta-1,3-glucan on the growth, survival, physiological and
      immune response of marron, Cherax tenuimanus (smith, 1912).
AB  - Six isonitrogenous and isocalorific diets supplemented with five different levels
      of beta-1,3-glucan (0.08%, 0.1%, 0.2%, 0.4% and 0.8%) were formulated and tested
      for marron (Cherax tenuimanus) growth, survival, organosomatic indices,
      osmoregulatory capacity and immunological parameters (total and differential
      haemocyte counts, haemolymph clotting time and bacteraemia). The sixth diet
      without any beta-1,3-glucan was used as a control. Each diet was provided to 18
      marron (0.47 +/- 0.02 g initial weight) replicated 3 times in individual 250 L
      fiberglass cylindrical tanks. Each tank was provided with a biological filtration
      recirculating water system. After 84 days of culture, the survival and yield were
      higher in the marron fed 0.1% beta glucan supplemented diet. The different levels
      of beta glucan did not alter any of the physiological parameters of marron.
      However, dietary supplementation with beta glucan resulted in significantly
      higher (P < 0.05) total haemocyte count (THC) and granular cells. The bacteraemia
      rank was lower in all diets having beta glucan supplemented with more than or
      equal to 0.1% compared to the control and 0.08% beta glucan supplemented diets.
      Results suggest that dietary beta-1,3-glucan at a minimum concentration of 0.1
      0.2% can improve the immune system of marron.

PMID- 20139009
TI  - Three dimensional echo-planar imaging at 7 Tesla.
AB  - Functional MRI (fMRI) most commonly employs 2D echo-planar imaging (EPI). The
      advantages for fMRI brought about by the increasingly popular ultra-high field
      strengths are best exploited in high-resolution acquisitions, but here 2D EPI
      becomes impractical for several reasons, including the very long volume
      acquisitions times. In this study at 7 T, a 3D EPI sequence with full parallel
      and partial Fourier imaging capability along both phase encoding axes was
      implemented and used to evaluate the sensitivity of 3D and corresponding 2D EPI
      acquisitions at four different spatial resolutions ranging from small to typical
      voxel sizes (1.5-3.0 mm isotropic). Whole-brain resting state measurements (N=4)
      revealed a better, or at least comparable sensitivity of the 3D method for gray
      and white matter. The larger vulnerability of 3D to physiological effects was
      outweighed by the much shorter volume TR, which moreover allows whole-brain
      coverage at high resolution within fully acceptable limits for event-related
      fMRI: TR was only 3.07 s for 1.5 mm, 1.88 s for 2.0 mm, 1.38 s for 2.5 mm and
      1.07 s for 3.0 mm isotropic resolution. In order to investigate the ability to
      detect and spatially resolve BOLD activation in the visual cortex, functional 3D
      EPI experiments (N=8) were performed at 1 mm isotropic resolution with parallel
      imaging acceleration of 3x3, resulting in a TR of only 3.2 s for whole-brain
      coverage. From our results, and several other practical advantages of 3D over 2D
      EPI found in the present study, we conclude that 3D EPI provides a useful
      alternative for whole-brain fMRI at 7 T, not only when high-resolution data are
      required.

PMID- 20139011
TI  - Focal epileptiform spikes do not show a canonical BOLD response in patients with
      benign rolandic epilepsy (BECTS).
AB  - Simultaneous EEG and functional MRI (EEG-fMRI) studies of focal epileptiform
      spikes commonly use the canonical haemodynamic response function (HRF) to model
      the blood-oxygenation-level-dependent (BOLD) response to these events. Support
      for the use of the canonical HRF has come from large studies that contain mixed
      cohorts of epilepsy syndromes and discharge types, and has demonstrated plausible
      epileptic localisation results in the majority of patients. Other studies,
      however, have reported that some patients show a BOLD response that differs
      markedly from a canonical HRF. Our aim in this study was to see if the BOLD
      response is well modelled by a canonical HRF in a homogeneous cohort of patients
      with benign epilepsy with centrotemporal spikes (BECTS), an idiopathic partial
      epilepsy with stereotypical centrotemporal spikes on the EEG. We studied eight
      well-characterised and typical BECTS patients and found that the shape of the
      average BOLD response was different to the canonical HRF. Furthermore, a
      localisation analysis using the group-average response provided increased
      sensitivity and specificity compared to the canonical HRF. Our findings suggest
      that the canonical HRF may not provide the best model for the BOLD response in
      some epilepsy syndromes or spike-types. In studies of homogeneous patient groups,
      therefore, localisation results may be improved by using a group-specific BOLD
      response.

PMID- 20139010
TI  - Mapping Alzheimer's disease progression in 1309 MRI scans: power estimates for
      different inter-scan intervals.
AB  - Neuroimaging centers and pharmaceutical companies are working together to
      evaluate treatments that might slow the progression of Alzheimer's disease (AD),
      a common but devastating late-life neuropathology. Recently, automated brain
      mapping methods, such as tensor-based morphometry (TBM) of structural MRI, have
      outperformed cognitive measures in their precision and power to track disease
      progression, greatly reducing sample size estimates for drug trials. In the
      largest TBM study to date, we studied how sample size estimates for tracking
      structural brain changes depend on the time interval between the scans (6-24
      months). We analyzed 1309 brain scans from 91 probable AD patients (age at
      baseline: 75.4+/-7.5 years) and 189 individuals with mild cognitive impairment
      (MCI; 74.6+/-7.1 years), scanned at baseline, 6, 12, 18, and 24 months.
      Statistical maps revealed 3D patterns of brain atrophy at each follow-up scan
      relative to the baseline; numerical summaries were used to quantify temporal lobe
      atrophy within a statistically-defined region-of-interest. Power analyses
      revealed superior sample size estimates over traditional clinical measures. Only
      80, 46, and 39 AD patients were required for a hypothetical clinical trial, at 6,
      12, and 24 months respectively, to detect a 25% reduction in average change using
      a two-sided test (alpha=0.05, power=80%). Correspondingly, 106, 79, and 67
      subjects were needed for an equivalent MCI trial aiming for earlier intervention.
      A 24-month trial provides most power, except when patient attrition exceeds 15
      16%/year, in which case a 12-month trial is optimal. These statistics may
      facilitate clinical trial design using voxel-based brain mapping methods such as
      TBM.

PMID- 20139012
TI  - Reduced neural selectivity increases fMRI adaptation with age during face
      discrimination.
AB  - Ventral-visual activity in older adults has been characterized by
      dedifferentiation, or reduced distinctiveness, of responses to different
      categories of visual stimuli such as faces and houses, that typically elicit
      highly specialized responses in the fusiform and parahippocampal brain regions
      respectively in young adults (Park et al., 2004). In the present study, we
      demonstrate that age-related neural dedifferentiation applies to within-category
      stimuli (different types of faces) as well, such that older adults process less
      distinctive representations for individual faces than young adults. We performed
      a functional magnetic resonance imaging adaptation experiment while young and
      older participants made same-different judgments to serially presented face-pairs
      that were Identical, Moderate in similarity through morphing, or Different. As
      expected, older adults showed adaptation in the fusiform face area (FFA), during
      the Identical as well as the Moderate conditions relative to the Different
      condition. Young adults showed adaptation during the Identical condition, but
      minimal adaptation to the Moderate condition. These results indicate that older
      adults' FFA treated the morphed faces as Identical faces, reflecting decreased
      fidelity of neural representation of faces with age.

PMID- 20139013
TI  - COMT Val(108/158)Met polymorphism effects on emotional brain function and
      negativity bias.
AB  - Biases toward processing negative versus positive information vary as a function
      of level of awareness, and are modulated by monoamines. Excessive biases are
      associated with individual differences in mood and emotional stability, and
      emotional disorder. Here, we examined the impact of the catechol-O
      methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and
      norepinephrine catabolism, on both emotional brain function and self-reported
      negativity bias. COMT genotyping and self-reported level of negativity bias were
      completed for 46 healthy participants taking part in the Brain Resource
      International Database. Functional MRI was undertaken during perception of facial
      expressions of fear and happiness presented under unmasked (consciously
      identified) and masked (to prevent conscious detection) conditions. Structural MR
      images were also acquired. A greater number of COMT Met alleles predicted
      increased activation in brainstem, amygdala, basal ganglia and medial prefrontal
      regions for conscious fear, but decreased activation for conscious happiness.
      This pattern was also apparent for brainstem activation for the masked condition.
      Effects were most apparent for females. These differences could not be explained
      by gray matter variations. The Met-related profile of activation, particularly
      prefrontally, predicted greater negativity bias associated with risk for
      emotional disorder. The findings suggest that the COMT Met allele modulates
      neural substrates of negative versus positive emotion processing. This effect may
      contribute to negativity biases, which confer susceptibility for emotional
      disorders.

PMID- 20139014
TI  - Spontaneous brain activity and EEG microstates. A novel EEG/fMRI analysis
      approach to explore resting-state networks.
AB  - The brain is active even in the absence of explicit input or output as
      demonstrated from electrophysiological as well as imaging studies. Using a
      combined approach we measured spontaneous fluctuations in the blood oxygen level
      dependent (BOLD) signal along with electroencephalography (EEG) in eleven healthy
      subjects during relaxed wakefulness (eyes closed). In contrast to other studies
      which used the EEG frequency information to guide the functional MRI (fMRI)
      analysis, we opted for transient EEG events, which identify and quantify brain
      electric microstates as time epochs with quasi-stable field topography. We then
      used this microstate information as regressors for the BOLD fluctuations. Single
      trial EEGs were segmented with a specific module of the LORETA (low resolution
      electromagnetic tomography) software package in which microstates are represented
      as normalized vectors constituted by scalp electric potentials, i.e., the related
      3-dimensional distribution of cortical current density in the brain. Using the
      occurrence and the duration of each microstate, we modeled the hemodynamic
      response function (HRF) which revealed BOLD activation in all subjects. The BOLD
      activation patterns resembled well known resting-state networks (RSNs) such as
      the default mode network. Furthermore we "cross validated" the data performing a
      BOLD independent component analysis (ICA) and computing the correlation between
      each ICs and the EEG microstates across all subjects. This study shows for the
      first time that the information contained within EEG microstates on a millisecond
      timescale is able to elicit BOLD activation patterns consistent with well known
      RSNs, opening new avenues for multimodal imaging data processing.

PMID- 20139015
TI  - Neuroelectric source imaging using 3SCO: a space coding algorithm based on
      particle swarm optimization and l0 norm constraint.
AB  - The electroencephalogram (EEG) neuroelectric sources inverse problem is usually
      underdetermined and lacks a unique solution, which is due to both the
      electromagnetism Helmholtz theorem and the fact that there are fewer observations
      than the unknown variables. One potential choice to tackle this issue is to solve
      the underdetermined system for a sparse solution. Aiming to the sparse solution,
      a novel algorithm termed 3SCO (Solution Space Sparse Coding Optimization) is
      presented in this paper. In 3SCO, after the solution space is coded with some
      particles, the particle-coded space is compressed by the evolution of particle
      swarm optimization algorithm, where an l0 constrained fitness function is
      introduced to guarantee the selection of a suitable sparse solution for the
      underdetermined system. 3SCO was first tested by localizing simulated EEG sources
      with different configurations on a realistic head model, and the comparisons with
      minimum norm (MN), LORETA (low resolution electromagnetic tomography), l1 norm
      solution and FOCUSS (focal underdetermined system solver) confirmed that a good
      sparse solution for EEG source imaging could be achieved with 3SCO. Finally, 3SCO
      was applied to localize the neuroelectric sources in a visual stimuli related
      experiment and the localized areas were basically consistent with those reported
      in previous studies.

PMID- 20139016
TI  - A three-dimensional digital atlas of the zebrafish brain.
AB  - In the past three decades, the zebrafish has become a vital animal model in a
      range of biological sciences. To augment current neurobiological research, we
      have developed the first three-dimensional digital atlas of the zebrafish brain
      from T2-weighted magnetic resonance histology (MRH) images acquired on a 16.4-T
      superconducting magnet. We achieved an isotropic resolution of 10 microm, which
      is the highest resolution achieved in a vertebrate brain and, for the first time,
      is comparable in slice thickness to conventional histology. By using manual
      segmentation, 53 anatomical structures, including fiber tracts as small as 40
      microm, were delineated. Using Amira software, structures were also individually
      segmented and reconstructed to create three-dimensional animations. Additional
      quantitative information including, volume, surface areas, and mean gray scale
      intensities were also determined. Finally, we established a stereotaxic
      coordinate system as a framework in which maps created from other modalities can
      be incorporated into the atlas.

PMID- 20139017
TI  - Nuclear and mitochondrial DNA sequence data reveal the evolutionary history of
      Barbus (Cyprinidae) in the ancient lake systems of the Balkans.
AB  - Freshwater fauna of ancient lakes frequently contain endemic taxa thought to have
      originated during the long existence of these lakes, yet uncertainties remain as
      to whether they represent distinct genetic lineages with respect to more
      widespread relatives and to the relative roles of isolation and dispersal in
      their evolution. Phylogenetic analyses of sequence variation at nuclear and
      mitochondrial genes were used to examine these issues for the freshwater fish
      genus Barbus in two European ancient lake systems on the Balkan Peninsula. The
      nuclear and mitochondrial data yielded concordant phylogeographic patterns though
      incomplete sorting of nuclear haplotypes between some mitochondrial clades was
      detected. The distributions of two currently recognized species investigated here
      do not match the distributions of evolutionary lineages revealed by phylogenetic
      analyses. The Prespa barbel, Barbus prespensis, is not endemic to the lakes
      Prespa as previously thought but is instead found to be widespread in the south
      eastern Adriatic Sea basin, with a distribution largely corresponding to the
      basin of the now extinct Lake Maliq historically connected with Lake Prespa. On
      the other hand, a cryptic phylogenetic subdivision in a widespread species, B.
      rebeli, was discovered to be more distant from B. rebeli than from other Barbus
      species and to be endemic to the system of connected lakes Ohrid and Shkodra. The
      division coincides with the hydrogeographical boundary delimiting distributions
      of other freshwater fishes, and we suggest that this newly discovered
      evolutionary lineage represents a distinct species. These findings support the
      emerging pattern that endemic taxa have evolved not through isolation of
      individual lakes, but in systems of currently and historically interconnected
      lakes and their wider basins.

PMID- 20139018
TI  - Multigene phylogenetic analysis of Lygodactylus dwarf geckos (Squamata:
      Gekkonidae).
AB  - The genus Lygodactylus is a group of small, diurnal geckos distributed mainly in
      Africa and Madagascar. A closely related, monotypic genus is Microscalabotes from
      Madagascar. We examined fragments of two moderate- to slow-evolving nuclear genes
      (RAG-1, RAG-2) and of two fast-evolving mitochondrial genes (16SrRNA, cytochrome
      b) to estimate phylogenetic relationships among 28 (of about 60) species
      (including Microscalabotes). Since cytochrome b provided little resolution for
      analysis of interspecific relationships in Lygodactylus, it was excluded from the
      concatenated Bayesian analysis. Our well-resolved Bayesian inference tree and its
      resulting clades confirm many previously suggested relationships among dwarf
      geckos based mainly on morphological characters, while several novel
      relationships lead us to regroup some species and to synonymize the genus
      Microscalabotes with the genus Lygodactylus. Our phylogenetic analysis well
      supports the monophyly of Lygodactylus (including Microscalabotes). However, it
      rejects monophyly of the Madagascan Lygodactylus. On the other hand, the data do
      not reject monophyly of the African forms. Though Africa is currently the main
      centre of diversity of Lygodactylus, our data suggest that the most parsimonious
      scenario would be a Madagascan origin, one dispersal to Africa, and one back to
      Madagascar.

PMID- 20139019
TI  - Phylogeography of endemic toads and post-Pliocene persistence of the Brazilian
      Atlantic Forest.
AB  - The Plio-Pleistocene refugia hypothesis recently gained support in explaining
      Brazilian Atlantic Forest megadiversity from combined analyses of species
      paleodistributions and genetic diversity. Here we examine genetic differentiation
      and historical distributions in the Rhinella crucifer group of toads, endemic to
      and widely distributed within this biome. We analyzed sequences of mitochondrial
      (control region, ND1, and ND2) and nuclear (beta-crystallin and rhodopsin) DNA
      markers from 65 individuals representing five species. We found deep structure
      across the range at mitochondrial markers; genetic diversity is geographically
      structured in four main haplotype clades with the oldest divergence, dated to the
      Pliocene, between the southernmost populations and other regions of the species'
      range. Remaining populations are distributed in haplotype clades that may have
      diverged throughout the Pleistocene. Our paleoecological distribution models
      support a scenario of habitat fragmentation associated with glacial cycling, but
      we found limited congruence of phylogeographic patterns with the refugia. We
      found that some genetic breaks geographically coincide with putative barriers
      associated to neotectonic activity, but finer-scale sampling will be necessary to
      test the relative importance of distinct isolation mechanisms. Overall, the data
      refute the recently proposed hypothesis of a southern Holocene colonization of
      the Atlantic Forest from northern refugia, suggesting instead persistence of
      forested habitats in the south. Our unexpected results underscore the need to
      consider distinct organismal histories in planning biome-level conservation. We
      discuss species correspondence to clades recovered in our phylogenetic analyses.

PMID- 20139020
TI  - Molecular phylogeny and historical biogeography of Nacella (Patellogastropoda:
      Nacellidae) in the Southern Ocean.
AB  - The evolution and the historical biogeography of the Southern Ocean marine
      benthic fauna are closely related to major tectonic and climatic changes that
      occurred in this region during the last 55 million years (Ma). Several families,
      genera and even species of marine organisms are shared between distant
      biogeographic provinces in this region. This pattern of distribution in marine
      benthic invertebrates has been commonly explained by vicariant speciation due to
      plate tectonics. However, recent molecular studies have provided new evidence for
      long-distance dispersion as a plausible explanation of biogeographical patterns
      in the Southern Ocean. True limpets of the genus Nacella are currently
      distributed in different biogeographic regions of the Southern Ocean such as
      Antarctica, Kerguelen Province, southern New Zealand Antipodean Province, North
      Central Chile and South American Magellanic Province. Here, we present
      phylogenetic reconstructions using two mitochondrial DNA markers (Cytochrome
      Oxidase I and Cytochrome b) to look into the relationships among Nacella species
      and to determine the origin and diversification of the genus. Phylogenies were
      reconstructed using two methods, Maximum Parsimony and Bayesian Inference, while
      divergence time among Nacella species was estimated following a relaxed Bayesian
      approach. For this purpose, we collected inter- and subtidal species belonging to
      four biogeographic regions in the Southern Ocean: Antarctica, Kerguelen Province,
      Central Chile, and Magellanic Province. Our molecular results agree with previous
      morphological and molecular studies supporting the monophyly of Nacella and its
      sister relationship with Cellana. Two rounds of diversification are recognized in
      the evolution of Nacella. The first one occurred at the end of the Miocene and
      gave rise to the main lineages, currently distributed in Antarctica, South
      America or Kerguelen Province. Large genetic divergence was detected among
      Nacella species from these distant biogeographic provinces emphasizing the
      significance of trans-oceanic discontinuities and suggesting long-distance
      dispersal was relatively unimportant. The second diversification round consisted
      of a more recent Pleistocene radiation in the Magellanic region. In this
      province, different morphological species of Nacella exhibit extreme low levels
      of genetic divergence with absence of reciprocal monophyly among them. According
      to our time estimation, the origin and diversification of Nacella in the Southern
      Ocean is more recent (<15 MY) than the expected under the hypothesis of vicariant
      speciation due to plate tectonics. The evolution of this genus seems to be
      closely related to drastic climatic and oceanographic changes in the Southern
      Ocean during the middle-Miocene climatic transition. In spite of the high number
      of species described for the Magellanic Province, molecular results indicate that
      these species are the most derived ones in the evolution of the genus and
      therefore that the Magellanic region does not need to correspond to the origin
      center of Nacella. The absence of genetic divergence among these species supports
      a very recent radiation process accompanied by rapid morphological and ecological
      diversification.

PMID- 20139021
TI  - Troubleshooting: Quantification of mobilization of progenitor cell subsets from
      bone marrow in vivo.
AB  - INTRODUCTION: The molecular mechanisms that control the mobilization of specific
      stem cell subsets from the bone marrow are currently being intensely
      investigated. It is anticipated that boosting the mobilization of these stem
      cells via pharmacological intervention will not only produce more effective
      strategies for bone marrow transplant patients, but also provide novel
      therapeutic approaches for tissue regeneration. METHODS: Measurement of stem cell
      mobilization by sampling peripheral blood is problematic because it is
      technically difficult to accurately determine absolute numbers of rare progenitor
      cells by blood sampling. Furthermore a rise in progenitors may be caused by
      release of stem cells from tissues other than the bone marrow (e.g. spleen and
      adipose), or indeed an inhibition of stem cell homing back to the bone marrow or
      other tissues. Finally it is not possible to distinguish whether the
      pharmacological agent is acting directly at the level of the bone marrow or
      mobilizing progenitors by a distinct indirect mechanism. To resolve these
      problems, we have developed a technique that allows perfusion of the vasculature
      of the hind limb bone marrow in situ in mice. In this system, the femoral artery
      and vein are cannulated in situ such that the femur and tibia bone marrow are
      perfused in isolation under anaesthesia. As such, pharmacological agents can be
      administered directly into the bone marrow vasculature. Mobilized cells are then
      collected via the femoral vein and colony assays performed in defined growth
      media to allow identification of haematopoietic, endothelial, and mesenchymal
      progenitor cells. We have used this system to determine the ability of a CXCR4
      antagonist to mobilize these distinct types of progenitor cells from the bone
      marrow of mice pre-conditioned with either G-CSF or VEGF. RESULTS AND CONCLUSION:
      This isolated hind limb perfusion system has allowed comparisons to be made
      between cytokines (G-CSF and VEGF) that act chronically, either alone or in
      combination with agents that act acutely on the bone marrow (CXCR4 antagonist) on
      their ability to directly mobilize specific populations of stem cells. Data
      obtained therefore gives a more accurate understanding of the efficacy of
      different mobilizing strategies compared to peripheral blood analysis.

PMID- 20139022
TI  - First report of Parabacteroides goldsteinii bacteraemia in a patient with
      complicated intra-abdominal infection.
AB  - Using 16S rRNA sequence analysis, we report the first isolation of
      Parabacteroides goldsteinii as a monobacterial isolate from blood culture in a
      patient with abdominal sepsis. P. goldsteinii phenotypically resembles
      Parabacteroides merdae and Parabacteroides distasonis and may be misidentified by
      commonly used enzymatic systems, suggesting that it may be more frequently
      present in clinical specimens than previously appreciated but either
      misidentified or ignored.

PMID- 20139024
TI  - Response to Letter from Demetrios S. Theodoropoulos, MD, DSc.

PMID- 20139023
TI  - Natural killer cell killing of acute myelogenous leukemia and acute lymphoblastic
      leukemia blasts by killer cell immunoglobulin-like receptor-negative natural
      killer cells after NKG2A and LIR-1 blockade.
AB  - Although the study of natural killer (NK) cell alloreactivity has been dominated
      by studies of killer cell immunoglobulin-like receptors (KIRs), we hypothesized
      that NKG2A and LIR-1, present on 53% +/- 13% and 36% +/- 18% of normal NK cells,
      respectively, play roles in the NK cell killing of primary leukemia targets. KIR(
      ) cells, which compose nearly half of the circulating NK cell population, exhibit
      tolerance to primary leukemia targets, suggesting signaling through other
      inhibitory receptors. Both acute myelogenous leukemia and acute lymphoblastic
      leukemia targets were rendered susceptible to lysis by fresh resting KIR(-) NK
      cells when inhibitory receptor-major histocompatibility class I interactions were
      blocked by pan-HLA antibodies, demonstrating that these cells are functionally
      competent. Blockade of a single inhibitory receptor resulted in slightly
      increased killing, whereas combined LIR-1 and NKG2A blockade consistently
      resulted in increased NK cell cytotoxicity. Dual blockade of NKG2A and LIR-1 led
      to significant killing of targets by resting KIR(-) NK cells, demonstrating that
      this population is not hyporesponsive. Together these results suggest that
      alloreactivity of a significant fraction of KIR(-) NK cells is mediated by NKG2A
      and LIR-1. Thus strategies to interrupt NKG2A and LIR-1 in combination with anti
      KIR blockade hold promise for exploiting NK cell therapy in acute leukemias.

PMID- 20139025
TI  - Long-term follow-up of an intensified myeloablative conditioning regimen with in
      vivo T cell depletion followed by allografting in patients with advanced multiple
      myeloma.
AB  - We report long-term results after a median follow-up of 105 months in 18 patients
      with multiple myeloma who received an intensified myeloablative conditioning
      regimen regimen consisting of modified total body irradiation, busulfan,
      cyclophosphamide, and antithymocyte globulin, followed by allogeneic stem cell
      transplantation (SCT). Grade II-IV acute graft-versus-host disease occurred in 7
      patients (44%), and treatment-related mortality was 17%. Complete remission (CR)
      with negative immunofixation after allogeneic SCT occurred in 53% of the
      patients. For all patients, the estimated overall survival at 12 years was 50%
      (95% confidence interval [CI], 26%-74%), and the estimated event-free survival
      (EFS) was 35% (95% CI, 23%-57%). Those patients who achieved CR after SCT had a
      12-year estimated PFS of 60%, whereas none of the patients without CR remained
      progression-free. Our data indicate that an intensified myeloablative
      conditioning regimen followed by allogeneic SCT can produce long-term survival
      and freedom from disease in patients with multiple myeloma who achieve CR.

PMID- 20139026
TI  - Oral symptom intensity, health-related quality of life, and correlative salivary
      cytokines in adult survivors of hematopoietic stem cell transplantation with oral
      chronic graft-versus-host disease.
AB  - Oral chronic graft-versus-host disease (cGVHD) is a frequent, clinically
      significant sequela of allogeneic hematopoietic stem cell transplantation (HSCT).
      This study was designed to elucidate relationships among clinical characteristics
      of oral cGVHD and related oral pain and oral dryness, salivary proinflammatory
      cytokine interleukin (IL)-6 and IL-1alpha concentrations, and health-related
      quality of life (HRQL). An understanding of the characteristics and correlates of
      oral cGVHD manifestations and related symptoms, such as oral dryness, is
      fundamental to the development of therapeutic interventions. Oral cGVHD severity
      was assessed with the Oral Mucositis Rating Scale (OMRS). Oral pain and perceived
      intensity of oral dryness were self-reported via a visual analog scale and a
      numeric rating scale, respectively. HRQL was assessed with the Functional
      Assessment of Cancer Therapy-General (FACT-G). Salivary IL-1alpha and IL-6
      concentrations were measured by enzyme-linked immunosorbent assay. All 42 adult
      subjects (59% males) had clinician-assessed oral cGVHD by the OMRS scale (mean
      score, 18.38 +/- 12.99; range, 2-46). Oral dryness (in 43% of subjects; mean OMRS
      score, 2.56 +/- 3.45; range, 0-10) was more prevalent than oral pain (8%; mean
      score, 0.13 +/- 0.47). Salivary IL-6 was associated with oral cGVHD severity (r =
      0.49; P < .01), oral ulceration (r = 0.38; P = .04), and erythema (r = 0.63; P <
      .01). FACT-G total score and physical and emotional well-being subscale scores
      were meaningfully lower than U.S. population normative values. Participants with
      more severe oral cGVHD manifestations had significantly inferior social/family
      well being (r = -0.49; P < .01). Oral dryness was associated with higher salivary
      IL-1alpha (r = 0.41; P = .04) and, controlling for cGVHD severity, with lower
      HRQL (r = -0.41; P = .03). Subjects with moderate to severe oral dryness tended
      to report the poorest overall HRQL. This study provides preliminary evidence of
      the relationship between oral dryness and HRQL, the contribution of oral cGVHD to
      inferior HRQL, and the association between IL-6 and oral cGVHD severity,
      ulceration, and erythema. The high prevalence of oral dryness and its
      relationship to HRQL in a sample of subjects with oral cGVHD underscores the
      importance of improving our evaluation and management of this symptom in long
      term survivors of allogeneic HSCT. The positive associations between IL-6 and
      oral cGVHD severity and erythema, as well as the positive trend with oral
      ulceration, warrant further exploration of this cytokine as a potential biomarker
      of active oral cGVHD.

PMID- 20139027
TI  - N-glycosylation at non-canonical Asn-X-Cys sequence of an insect recombinant
      cathepsin B-like counter-defense protein.
AB  - CmCatB, a cowpea bruchid cathepsin B-like cysteine protease, facilitates insects
      coping with dietary protease inhibitor challenge. Expression of recombinant
      CmCatB using a Pichia pastoris system yielded an enzymatically active protein
      that was heterogeneously glycosylated, migrating as a smear of > or =50kDa on SDS
      PAGE. Treatment with peptide:N-glycosidase F indicated that N-glycosylation was
      predominant. CmCatB contains three N-glycosylation Asn-X-Ser/Thr consensus
      sequences. Simultaneously replacing all three Asn residues with Gln via site
      directed mutagenesis did not result in completely unglycosylated protein,
      suggesting the existence of additional atypical glycosylation sites. We
      subsequently investigated potential N-glycosylation at the two Asn-X-Cys sites
      (Asn(100) and Asn(236)) in CmCatB. Asn to Gln substitution at Asn(100)-X-Cys on
      the background of the double mutation at the canonical sites (m1m2, Asn(97)-->Gln
      and Asn(207)-->Gln) resulted in a single discrete band on the gel, namely m1m2c1
      (Asn(97)-->Gln, Asn(207)-->Gln and Asn(100)-->Gln). However, another triple
      mutant protein m1m2c2 (Asn(97)-->Gln, Asn(207)-->Gln and Asn(236)-->Gln) and
      quadruple mutant protein m1m2c1c2 were unable to be expressed in Pichia cells.
      Thus Asn(236) appears necessary for protein expression while Asn(100) is
      responsible for non-canonical glycosylation. Removal of carbohydrate moieties,
      particularly at Asn(100), substantially enhanced proteolytic activity but
      compromised protein stability. Thus, glycosylation could significantly impact
      biochemical properties of CmCatB.

PMID- 20139028
TI  - Locust adipokinetic hormones mobilize diacylglycerols selectively.
AB  - The diacylglycerols (DG) molecular species and their fatty acid (FA) composition
      were investigated by electrospray mass spectrometry (ESI-MS) and by gas
      chromatography with flame ionisation detection (GC-FID) in haemolymph of Locusta
      migratoria after application of adipokinetic hormones Locmi-AKH-I, -II and -III.
      The analyses showed (1) a heterogeneous distribution of individual DGs in
      haemolymph after the hormone application. The results revealed that mobilization
      of the DGs is molecular species-specific with the highest proportion of 34:1 DG
      (16:0/18:1 - mw 594Da) for all Locmi-AKHs bearing palmitic acid (C16:0) and oleic
      acid (C18:1) residues, and forming about 20% of the total mobilized DG content.
      (2) Analysis of fat body triacylglycerols revealed that all Locmi-AKHs mobilize
      the DGs selectively with the preference of those possessing the C18 and C16 FAs.
      The fat body FAs with carbon chain longer than 18 did not participate in the
      mobilization. (3) A distribution of FAs in the DG structures obtained by LC/ESI
      MS, and FA analysis by GC-FID after transmethylation indicated a certain degree
      of Locmi-AKH selectivity toward the mobilized DGs and hence the FAs. The Locmi
      AKH-I significantly prefers mobilization of DGs containing unsaturated FAs, while
      Locmi-AKH-II and -III prefer mobilization of saturated FAs.

PMID- 20139029
TI  - The in vitro genotoxicity of orthopaedic ceramic (Al2O3) and metal (CoCr alloy)
      particles.
AB  - One of the biggest problems with orthopaedic joint replacements has been the
      tendency for metal-on-polyethylene implants to produce particulate wear debris.
      These particles stimulated adjacent macrophage infiltration, which caused
      destruction of bone and soft tissue, resulting in aseptic loosening of the
      implant. This problem led to the development of new implants with articulating
      surfaces that produce less volumetric wear (metal-on-metal, MOM, and ceramic-on
      ceramic, COC). To determine whether there could be adverse biological effects
      from exposure to particulate wear debris after total hip replacement (THR), we
      investigated the in vitro genotoxic effects of alumina ceramic (Al(2)O(3))
      particles in comparison with cobalt-chrome metal (CoCr alloy) particles. Primary
      human fibroblasts were exposed to Al(2)O(3) nanoparticles or CoCr alloy particles
      (0.1-10mg/T-75 flask) for 5 days. There were no significant differences in cell
      viability between control and ceramic-treated cells, at all doses and time-points
      studied. Cells exposed to CoCr alloy particles showed both dose- and time
      dependent cytotoxicity. There was a small but significant increase in
      micronucleated binucleate cells after 24h of treatment with >1mg/T-75 flask of
      alumina particulates compared with controls, although no clear dose-response was
      observed. The induction of micronuclei was unaffected by the size or shape of the
      ceramic particles. The increase in micronucleated binucleate cells was much
      greater after exposure to CoCr particles for 24h, showing a clear dose-response
      curve. No increase in gamma-H2AX foci was noted in cells exposed to ceramic
      particles, in contrast with a significant increase of these foci in cells exposed
      to CoCr particles at comparable mass/surface doses. Cytogenetic analysis showed
      that both types of particle caused mainly numerical rather than structural
      chromosomal aberrations, with a greater number and variation of lesions induced
      by CoCr particles. In conclusion, our results show that alumina (Al(2)O(3))
      ceramic particles are only weakly genotoxic to human cells in vitro when compared
      with metal (CoCr alloy) particles.

PMID- 20139030
TI  - Comparison between two kinds of cigarette smoke condensates (CSCs) of the
      cytogenotoxicity and protein expression in a human B-cell lymphoblastoid cell
      line using CCK-8 assay, comet assay and protein microarray.
AB  - The differences of the cytogenotoxicity and proteins expression of human B-cell
      lymphoblastoid cells exposed to cigarette smoke condensates (CSCs) from two kinds
      of cigarettes were detected with CCK-8 assay, comet assay, protein microarray and
      western blot assay in vitro. Human B-cell lymphoblastoid cell line was exposed to
      CSCs from two cigarettes (which delivers approximately 3mg tar, 0.3mg nicotine,
      3mg CO per cigarette for cigarette 1 and 15mg tar, 1.3mg nicotine, 15mg CO per
      cigarette for cigarette 2), and the exposure doses were 2.5, 5.0, 7.5, 10.0 and
      12.5x10(-3)cigarettes/ml of CSCs for 24h in CCK-8 assay, 6.0, 8.0, 10.0, 12.0 and
      14.0x10(-3)cigarettes/ml of CSCs for 4h in comet assay, and 10.0x10(
      3)cigarettes/ml of CSCs for 4h in protein levels analysis. The results of CCK-8
      assay and comet assay in the present study suggested that the cytogenotoxicity in
      cigarette 2 group was significantly higher than that in cigarette 1 group. The
      results of protein microarray and western blot assay showed that there were the
      differences of the expression levels of four proteins (i.e., RAR-beta, 14-3-3
      sigma, XPF, and p57(Kip2) Ab-7) between cigarette 1 group and cigarette 2 group.
      Hence, it is possible that the RAR-beta, 14-3-3 sigma, XPF, and p57(Kip2) Ab-7
      proteins serve as the molecular biomarkers in studying the cytogenotoxicity
      induced by CSCs.

PMID- 20139031
TI  - Tryptase promotes human monocyte-derived macrophage foam cell formation by
      suppressing LXRalpha activation.
AB  - Accumulated mast cells in atherosclerotic plaques secrete a high level of
      tryptase that may participate in the pathogenesis of atherosclerotic disease by
      diverse pathways. However, the role of tryptase in the lipid metabolism of
      macrophages remains to be defined. In the present study, we found that the
      addition of tryptase into THP-1-derived macrophages increased both intracellular
      lipid accumulation and total cholesterol level. Tryptase promoting foam cell
      formation was also observed by transmission electron microscope. These effects
      were resisted by APC366, a selective inhibitor of mast cell tryptase. Tryptase
      dramatically resisted 22RHC induced activation of LXRalpha protein expression,
      which can be reversed by SAM-11 (a PAR-2-specific neutralizing antibody) and
      reduced LXRalpha, ABCG1, ABCA1 and SREBP-1c mRNA levels and ABCG1 protein level,
      which were all blocked by APC366. PAR-2 agonist also redeemed 22RHC stimulation
      to activate LXRalpha, ABCG1 protein expression, and mRNA levels of LXRalpha and
      its target genes in both THP-1-derived macrophages and primary human monocyte
      derived macrophages. In primary macrophages that were first transfected with PAR
      2 siRNA and then treated with tryptase, both the ABCG1 protein level and mRNA
      levels of LXRalpha and ABCG1 were higher than those in the control siRNA-treated
      cells. Taken together, our data clarified the PAR-2 expression of human
      macrophages and suggested that tryptase might promote lipid accumulation in
      macrophages and foam cell formation by suppressing LXRalpha activation via PAR
      2/LXRalpha/LXRalpha target genes signaling pathway. This investigation sheds a
      new light on the role of tryptase in foam cell formation and pathogenesis of
      atherosclerosis.

PMID- 20139032
TI  - Ammodytoxin content of Vipera ammodytes ammodytes venom as a prognostic factor
      for venom immunogenicity.
AB  - Venoms are complex mixtures of proteins, peptides and other compounds whose
      biochemical and biological variability has been clearly demonstrated. These
      molecules have been used as antigens for immunization of anti-venom-producing
      animals (horses or sheep). Ammodytoxins (Atx) are potently neurotoxic compounds,
      and the most toxic compounds isolated so far from the Vipera ammodytes ammodytes
      (Vaa) venom. Recently we have shown that the level of antibodies specific to Vaa
      venom's most toxic component, ammodytoxin A (AtxA), (anti-AtxA IgG) in Vaa venom
      immunized rabbit sera highly correlated to the venom toxicity-neutralization
      potential of these sera. Here we investigated whether Atx content of Vaa venom
      could influence the outcome of immunization procedure. The novel ELISA was
      developed for precise determination of Atx content and Atx was quantified in
      venom samples used for immunization of rabbits. We clearly showed that animals
      immunized with the venom containing lower amount of Atx produced sera with
      significantly lower venom toxicity-neutralizing power and, vice versa, animals
      immunized with venoms containing higher amount of Atx produced sera with higher
      venom toxicity-neutralizing ability. Thus, the content of Atx in Vaa venom is a
      relevant parameter of its suitability in the production of highly protective Vaa
      anti-venom.

PMID- 20139033
TI  - Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of
      Crohn's disease.
AB  - BACKGROUND & AIMS: Infliximab might prevent postsurgical recurrence of Crohn's
      disease. However, it is unclear whether long-term therapy is necessary and
      whether alternative strategies could be applied to minimize potential side
      effects and reduce the costs of treatment. METHODS: We performed a prospective
      cohort study in 12 consecutive patients, treated immediately after surgery with
      maintenance infliximab (5 mg/kg), who did not have clinical or endoscopic
      evidence of disease recurrence after 24 months; they were followed up for an
      additional year. Infliximab treatment was then discontinued; patients with
      disease recurrence, based on endoscopy (Rutgeerts score, >or=2), were given lower
      doses of infliximab (starting with 1 mg/kg) to re-establish mucosal integrity.
      Surrogate markers of disease activity (fecal calprotectin [FC], C-reactive
      protein, and erythrocyte sedimentation rate) were assessed after each infliximab
      dose. RESULTS: None of the patients had clinical or endoscopic recurrence of
      Crohn's disease 3 years after surgery. However, discontinuation of infliximab
      caused endoscopic recurrence after 4 months in 10 of 12 patients (83%). All 10
      patients then were treated again with infliximab, which, at a dose of 3 mg/kg
      every 8 weeks, restored and maintained mucosal integrity for 1 year. Among the
      surrogate markers, FC levels correlated with endoscopic scores (Wald test, P <
      .0001). CONCLUSIONS: Long-term maintenance therapy with infliximab is required to
      maintain mucosal integrity in patients after surgery for Crohn's disease.
      However, a dose of 3 mg/kg (a 40% reduction from the standard dose) was
      sufficient to avoid disease recurrence, determined by endoscopy, in all patients
      at 1 year. FC levels correlate with mucosal status at different infliximab doses.

PMID- 20139034
TI  - Elucidating the spread of the emerging canid nematode Angiostrongylus vasorum
      between Palaearctic and Nearctic ecozones.
AB  - Angiostrongylus vasorum is an emerging parasite that is currently distributed
      through Western Europe and parts of South America. An isolated population is also
      present in Newfoundland, Canada. This presents a risk of onward spread into North
      America, but its origin is unknown. To ascertain the phylogeographic
      relationships and genetic diversity of A. vasorum within the western Palaearctic
      and eastern Nearctic ecozones, a total of 143 adult and larval nematode specimens
      were collected from foxes (Vulpes vulpes) and dogs (Canis lupus familiaris) in
      Canada, Denmark, France, Germany, Ireland, the Netherlands, Portugal and the
      United Kingdom, and a coyote (Canis latrans) in Canada. DNA was extracted and the
      second internal transcribed spacer and two mitochondrial loci were amplified and
      sequenced. Multiple haplotypes (n=35) based on combined mitochondrial sequences
      (1078bp) of the partial cytochrome oxidase subunit I (COI), large subunit
      ribosomal RNA (rrnL) and the complete nicotinamide adenine dinucleotide
      dehydrogenase 3 (NADH3) sequences, were observed throughout the Palaearctic
      countries sampled; however, only a single haplotype was observed for the Canadian
      A. vasorum population. The likely origin of A. vasorum in Newfoundland is
      therefore inferred to be within the western Palaearctic. There was no evidence of
      genetic segregation of parasites in dogs, foxes and coyotes, supporting the
      hypothesis that transmission occurs between wild and domestic canids. The
      transmission dynamics and population structure of this nematode are further
      discussed.

PMID- 20139035
TI  - Accumulated immune complexes of IgE and omalizumab trap allergens in an in vitro
      model.
AB  - The best understood mechanisms of omalizumab are that it neutralizes free IgE and
      down-regulates high-affinity IgE.Fc receptors (FcepsilonRI) on basophils and mast
      cells. It has been proposed that since complexes of IgE and omalizumab are
      accumulated to 5-10 times the basal levels of IgE, they may trap incoming
      allergens, contributing to omalizumab's effectiveness. In order to investigate
      the ability of IgE:omalizumab complexes in trapping allergens and inhibiting
      basophil activation in an in vitro reconstitution model, the ability of
      IgE:omalizumab complexes to tie up antigen and hence inhibit (a) antigen binding
      to IgE bound by FcepsilonRI, and (b) antigen-mediated activation of basophils,
      was examined. The free IgE was prepared by mixing different proportions of
      antigen-nonspecific IgE secreted by U266 cells and antigen-specific IgE, SE44
      IgE, which recognizes a synthetic 15 a.a. peptide, R15K. The antigen was
      (R15K)(8)-ova, i.e. ovalbumin conjugated with an average of 8 copies of R15K per
      molecule. The solid-phase FcepsilonRI was a recombinant protein representing the
      extracellular portion of the alpha chain of the FcepsilonRI receptor complex. The
      model FcepsilonRI(+) basophilic cell line was RBL.SX-38, a rat basophilic
      leukemic line transfected with the genes for alpha, beta and gamma subunits of
      human FcepsilonRI. The results showed that the IgE:omalizumab complexes trapped
      increasing amounts of antigen with increasing (a) concentration of IgE, (b)
      proportion of antigen-specific IgE in total IgE, and (c) concentration of total
      immune complexes. Such trapping decreased the antigen-induced activation of
      FcepsilonRI(+) cells that had been pulsed with antigen-specific IgE, resulting in
      decreased mediator release. These results suggest that the rapidly accumulated
      IgE:omalizumab complexes in omalizumab-treated patients can capture allergens and
      consequently contribute to the pharmacological effects of omalizumab.

PMID- 20139036
TI  - Utility of DNA methylation markers for diagnosing cancer.
AB  - DNA methylation occurs at the CpG residues and serves as a powerful epigenetic
      mechanism that negatively regulates gene expression. This process is catalyzed by
      DNA methyltransferases and occurs within "CpG islands" found in the promoter
      regions of >70% of human genes. Given the important role of DNA methylation in
      regulating gene expression, un-programmed changes in methylation patterns are
      expected to either silence or activate transcription of tumor suppressor genes
      (via hypermethylation) or oncogenes (via demethylation), respectively, and by
      doing so promote a disease state. In light of the fact that a number of different
      cancers are frequently associated with hypermethylated tumor suppressor genes
      together with the observation that tumor derived genomic DNAs are present in
      various body fluids including serum/plasma, urine, sputum and bronchial lavage,
      methylated DNA has shown tremendous promise to serve as a robust biomarker for
      detecting cancer. Over the last several years protocols for capturing small
      amounts of DNA in circulation have been developed. Once captured, DNA methylation
      may be readily monitored by restriction enzyme digestion or bisulfite conversion
      followed by amplification of the desired genomic region with the polymerase chain
      reaction (PCR). New technologies which employ methyl-binding protein or
      antibodies that bind specifically to methylated-CpG residues have now enabled
      investigators to interrogate the status of entire "DNA methyome" of diseased
      tissue in an efficient and cost-effective manner. In this review, we describe the
      various tumor suppressor genes that are frequently hypermethylated in different
      cancers and how these and other methylated loci may be employed as clinically
      useful biomarkers for diagnosing cancer noninvasively using readily available
      body fluids.

PMID- 20139037
TI  - Protein biomarker discovery for head and neck cancer.
AB  - Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common
      cancer worldwide. Despite improvements in diagnosis and treatment, the five-year
      survival rate of advanced HNSCC has only moderately increased, which is largely
      due to the high proportion of patients that present with advanced disease stage
      and the frequent development of relapse and second primary tumors. Protein
      biomarkers allowing early detection of primary HNSCC or relapse may aid to
      improve clinical outcome. Screening for precursor changes in the mucosal linings
      preceding the development of invasive tumors and for accurate prediction of risk
      of malignant transformation, may be propitious opportunities, which are as yet
      difficult. This review summarizes recent results in HNSCC proteomics for
      biomarker research. Despite the wide diversity of experimental designs, a few
      common markers have been detected. Although some of these potential biomarkers
      are very promising, they still have to be further clinically validated. Finally,
      treatment of advanced cancers of several sites within the head and neck has
      shifted significantly during the last decade, and also, targeted drugs have
      entered the clinic. This has major consequences for the research questions in
      HNSCC research and accordingly for the future direction of proteome research in
      HNSCC biomarker discovery.

PMID- 20139038
TI  - Chromatin dynamics during herpes simplex virus-1 lytic infection.
AB  - Herpes simplex virus type 1 is a DNA virus that can establish lytic infections in
      epithelial cells and latent infections in sensory neurons. Upon entry into the
      nucleus the genome of HSV-1 rapidly associates with histone proteins. Similar to
      the genomes of the cellular host, HSV-1 is subject to chromatin-based regulation
      of transcription and replication. However, unlike the host genome, nucleosomes
      appear to be underrepresented on the HSV genome. During lytic infection, when the
      genome is transcribed, the HSV-1 chromatin structure appears to be disorganized,
      and characterized by histone variant sub-types and post-translational
      modifications representative of active chromatin. In contrast, during latency,
      when the majority of the viral genome is transcriptionally silent, the chromatin
      is compacted into a regularly repeating, compact heterochromatic structure. Here
      we discuss recent studies that underscore the importance of chromatin regulation
      during the lytic phase of the HSV-1 life-cycle.

PMID- 20139039
TI  - Growth restriction of an experimental live attenuated human parainfluenza virus
      type 2 vaccine in human ciliated airway epithelium in vitro parallels attenuation
      in African green monkeys.
AB  - Human parainfluenza viruses (HPIVs) are common causes of severe pediatric
      respiratory viral disease. We characterized wild-type HPIV2 infection in an in
      vitro model of human airway epithelium (HAE) and found that the virus replicates
      to high titer, sheds apically, targets ciliated cells, and induces minimal
      cytopathology. Replication of an experimental, live attenuated HPIV2 vaccine
      strain, containing both temperature sensitive (ts) and non-ts attenuating
      mutations, was restricted >30-fold compared to rHPIV2-WT in HAE at 32 degrees C
      and exhibited little productive replication at 37 degrees C. This restriction
      paralleled attenuation in the upper and lower respiratory tract of African green
      monkeys, supporting the HAE model as an appropriate and convenient system for
      characterizing HPIV2 vaccine candidates.

PMID- 20139040
TI  - Cold agglutinin-induced acrocyanosis in a patient with subclinical chronic
      lymphocytic leukemia; a beneficial response to rituximab.

PMID- 20139041
TI  - Stroke evaluation and treatment.
AB  - Cerebrovascular accidents remain the third leading cause of death in the United
      States, with many left with life-long disabilities. The causes and contributing
      factors of stroke are beginning to be well defined, but what is not appreciated
      are the various techniques for assisting recovery. Understanding what parts of
      the neurological and musculoskeletal exams predict short-term and long-term
      disabilities helps guide patients and families. Newer and effective
      rehabilitative approaches are available as are home, outpatient, and hospital
      based sites for recovery. Improvements after stroke are now recognized to
      continue for months to years after the event. Available therapeutic techniques
      and evaluative studies are presented in this review.

PMID- 20139042
TI  - Team assessment in stroke rehabilitation.
AB  - Goal planning is one of the most universal approaches in rehabilitation, yet its
      application is much more than just setting specific behavior-focused goals. This
      article aims to emphasize the fundamental aspects of the process and reference
      the key literature in the area. At its heart, goal planning is about producing
      lasting behavior change, and the central role of the patient in the assessment
      and rehabilitation process is highlighted throughout. The team-based nature of
      assessment is promoted and the benefit of measuring verbal (a patient's knowledge
      of his or her condition and ability to instruct others in its management) as well
      as physical capability, as incorporated by one of the measures, is discussed. A
      hierarchical approach to the setting of goals is suggested so that individual
      patient need can be reflected in the process rather than setting goals which
      centre on specific professional skills. The article provides information about
      the long-term benefits for the patient and service that arise from this change of
      emphasis and maps the goal-planning process onto an adjustment model. Practical
      case examples of patient involvement in the assessment and goal-setting process
      are given.

PMID- 20139043
TI  - Assessment of stroke survivors: assisting families of stroke survivors on acute
      rehabilitation units.
AB  - Stroke affects a significant number of individuals in the United States each
      year, leaving survivors with varying levels of physical or cognitive impairments.
      Because of the sudden onset of symptoms that can result in physical and cognitive
      changes, a stroke can be viewed as a crisis in many families. Family members are
      often the primary caretakers of stroke survivors, and this article reviews the
      literature on the need for providing families with support and education and the
      issues related to discharge and after-care and caretaker coping. Education and
      support while the patient is on an acute rehabilitation unit is therefore
      essential and is the focus of this article. Suggestions for working with families
      and sharing information related to neuropsychological testing data and
      rehabilitation progress are also given.

PMID- 20139044
TI  - Effects of right hemisphere strokes on personality functioning.
AB  - Strokes affecting large areas of the right hemisphere are common. However, many
      of the most frequently seen deficits that accompany such strokes are
      underassessed, go untreated, and are never reported or described to family
      members or patients. Too often, this creates devastating but avoidable
      consequences. As a result, many individuals return to their homes with family
      members who cannot understand their behavior changes, who do not seek appropriate
      treatment for the stroke-injured person, and who cannot come to an acceptance of
      the individual's strengths and limitations. This article discusses those deficits
      to remind those working with right hemisphere stroke patients of the importance
      of considering them when assessing and treating these individuals and when
      working with their family members.

PMID- 20139045
TI  - Mutual trust: the key to successful assessment and treatment.
AB  - When we first meet the individual who has just had a stroke and their family
      members, we have an opportunity to set the stage for the individual's long-term
      adjustment to the effects of their cerebrovascular event. Or we can squander that
      opportunity. By using an empathetic approach with individuals, we can often have
      a dramatically positive effect on adjustment and outcome over time. Building
      trust can make all the difference. When an individual is compromised by stroke,
      the family can become the bridge between the patient and the staff by providing
      the vital information needed to build trust. The assessment process gives the
      staff an opportunity to develop a trusting relationship with the individual and
      their family members. Only the investment of time on the part of the staff will
      guarantee the opportunity to develop and establish the rapport needed for
      effective treatment outcomes.

PMID- 20139046
TI  - Rehabilitation length of stay in patients suffering from aphasia after stroke.
AB  - BACKGROUND AND PURPOSE: Few studies have assessed the relationship between
      aphasia and rehabilitation length of stay (LOS). The aim of the current
      prospective study was to evaluate LOS in patients with aphasia and its relation
      to functional improvement. METHODS: The study was performed in 252 patients
      admitted for rehabilitation follow-up of their first stroke (126 patients with
      aphasia and hemiparesis [aphasia group] and 126 patients with hemiparesis but
      without aphasia [control group]). All patients were submitted to clinical,
      neurological, and neuropsychological examinations. The following tests were
      performed: Aachen Aphasia Test, Albert's test, anosognosia scale, Cumulative
      Illness Rating Scale (CIRS), Fugl-Meyer Scale, and FIM. RESULTS: LOS was 50.7 and
      46.7 days in the aphasia and control groups, respectively. There was no
      statistically significant difference in the LOS between aphasia and control
      groups (p = .056). A longer LOS was correlated with low admission aphasia score
      (r = -0.19). The increase in motor FIM per day obtained by therapy (LOS-Eff) was
      0.54 +/- 0.3 in the aphasia group and 0.75 +/- 0.5 in the control group. The LOS
      Eff was significantly poorer in the aphasia group (p = .000). A high LOS-Eff was
      correlated with high aphasia score (r = 0.31). In multivariate regression
      analyses, aphasia was an important predictor of LOS-Eff (beta = 0.18).
      CONCLUSIONS: In patients with aphasia, LOS is few days longer and LOS-Eff is
      significantly poorer compared to patients without aphasia. Aphasia is a
      significant independent predictor of LOS-Eff at discharge.

PMID- 20139047
TI  - Vision-related quality of life in patients with complete homonymous hemianopia
      post stroke.
AB  - PURPOSE: The aim is to determine the characteristics of vision-specific quality
      of life restriction using the National Eye Institute Visual Function
      Questionnaire (NEI VFQ-25) and Veterans Affairs Low Vision Visual Function
      Questionnaire (VA LV VFQ-48) in patients with complete homonymous hemianopia (HH)
      post stroke. METHOD: Prospective cohort study of patients with complete HH
      compared to age- and gender-matched subjects with normal visual fields. RESULTS:
      In the NEI VFQ-25, scores on five subscales were significantly reduced after
      multiple logistic regression accounting for vision and comorbidities. The five
      subscales are vision-specific social functioning, vision-specific mental health,
      vision-specific dependency, driving, and peripheral vision. In the VA LV VFQ-48
      postregression analysis, mobility is the only domain that is significantly
      affected in the people with HH. CONCLUSION: Identification of the significant
      areas of visual difficulties and their effects on quality of life is important as
      it can help better address the patients' rehabilitation needs. The current study
      identifies the need for orientation and mobility training as well as independent
      living rehabilitation in patients with HH to help address the difficulties in
      their vision-specific quality of life and maximize their residual vision.

PMID- 20139048
TI  - Falling through the cracks: a literature review to understand the reality of mild
      stroke survivors.
AB  - PURPOSE: To review the existing literature on mild stroke, its consequences for
      patients and families, and the effectiveness of rehabilitation services targeting
      mild stroke. METHOD: A systematic search was conducted on Ovid (EMBASE and
      MEDLINE, 1950-2008), PubMed, CINAHL, and Cochrane (to 4th quarter 2008). Articles
      had to be written in French or English. The term "mild stroke" was combined with
      a variety of key words. Titles, abstracts, and results sections were screened,
      and the sample had to be composed of not greater-than 50% mild stroke. Two
      reviewers were involved in the selection process to ensure the research was
      reproducible and that all the literature was screened properly. RESULTS: Thirteen
      articles meeting inclusion and exclusion criteria were found. Mild stroke
      survivors may present impairments that do not interfere with basic activities of
      daily living but do affect performance of complex tasks. The consequences for
      families remain unknown. Home interventions were found to help patients maximize
      their functions and reduce stroke sequelae. CONCLUSION: The majority of mild
      stroke survivors are sent home without referral to rehabilitation services
      although they present deficits that, if not addressed, can lead to deconditioning
      and impede community reengagement. The impact of mild stroke on families needs to
      be studied.

PMID- 20139049
TI  - Evidence-Based Review of Stroke Rehabilitation: executive summary, 12th edition.

PMID- 20139050
TI  - Stem cells, DNA damage, ageing and cancer.
AB  - A comprehensive knowledge of adult stem cells not only sheds light on their
      significant roles in many fundamental biological process, but also on their
      implications in a variety of deleterious disorders including leukemia, lymphoma,
      ageing and other relevant degenerative disorders. Elucidating the diverse
      signaling pathways in stem cells paves the way for development of targeted
      therapeutic approaches against degenerative disorders. Despite emerging studies,
      our understanding of the key molecular machineries that profoundly influence key
      stem cell properties is poor. This review discusses the seminal aspects of stem
      cell self-renewal mechanisms with an emphasis on various influencing factors,
      including DNA damage, and intrinsic and extrinsic factors that govern the
      significant characteristics of tissue stem cells under normal and stress
      conditions. Also outlined are intriguing aspects of how molecular interventions
      in key stem cell pathways could be exploited to develop novel therapies against
      stem cell disorders.

PMID- 20139051
TI  - Newly diagnosed multiple myeloma in Taiwan: the evolution of therapy, stem cell
      transplantation and new treatment agents.
AB  - Multiple myeloma is a clonal plasma cell dyscrasia with clinical heterogeneity.
      As of now, two key questions need to be answered before starting to treat a newly
      diagnosed myeloma patient. One is whether the patient is a candidate for high
      dose chemotherapy with stem cell support and the other is risk stratification. As
      novel therapeutics have emerged, it is increasingly important to introduce a risk
      adapted approach. The heterogeneity of the disease is established, for the most
      part, by disease biology, predominantly genetics. Cytogenetic analysis by either
      banding technique or fluorescent in situ hybridization is able to identify high
      risk subpopulations. The new international staging system based on beta2
      microglobulin and albumin levels in serum is also very helpful in defining the
      high-risk group (stage 3). This group of patients may not respond well to high
      dose chemotherapy and require early introduction of newer treatments such as the
      bortezomib-containing regimen. The main factor in determining the eligibility for
      stem cell transplants is age. Based on the current literature and situation in
      Taiwan, we suggest stem cell transplantation if the patient is younger than 55
      years of age. Each case should be considered individually if the age of the
      patient is between 55 and 70 years. Finally, we have also reviewed the status and
      the treatment of multiple myeloma in Taiwan. Fortunately, there has been an
      improvement in awareness, diagnosis and treatment. Cytogenetic studies have been
      applied in risk evaluations, but are limited in a few centers due to lack of
      availability. With the exception of the agent lenalidomide, new novel agents are
      available for treating of myeloma in Taiwan.

PMID- 20139052
TI  - Validation of tissue microarray biomarker expression of breast carcinomas in
      Saudi women.
AB  - BACKGROUND: Analysis of immunohistochemical expression of a large number of tumor
      tissue samples with conventional techniques is costly, tedious and slow. Tissue
      microarray (TMA) technology can facilitate the sampling of over 500 tumors on a
      one-glass slide, which then can be analyzed by fluorescence in situ hybridization
      (FISH), RNA in situ hybridization, or immunohistochemistry. We attempted to
      validate this technique in breast cancer specimens by comparing the staining
      result obtained by TMA with the conventional whole-section method. PATIENTS AND
      METHODS: Eighty cases of breast cancer of diverse subtypes were used to build a
      breast cancer biomarker evaluation model. Serial sections of the recipient block
      were immunostained with a panel of 4 anti- bodies (ER, PR, HER2 and p53).
      Concordance of immunohistochemical expression between TMA sections and whole
      sections was expressed as a kappa statistic. RESULTS: Target tumors were
      accurately sampled by two cores in 19 of 26 donor blocks, and by only one core in
      5 blocks. Failure to sample tumor was seen in 2 blocks. Concordance between the
      staining results of TMA and whole sections was good for PR (kappa=0.67) and ER
      (kappa=0.67) and very good for p53 (kappa=0.91) and HER2 (kappa=0.91), when all
      the 26 recipient blocks were included. The rate improved to excellent for p53
      (kappa=1.0) and did not change for the other markers when concordance analysis
      was limited to recipient blocks that had been sampled by two cores. CONCLUSION:
      TMA is a reliable technique for examining a large set of tumors. It shows
      immunostaining scores comparable to those obtained by conventional whole-section
      evaluation in breast cancer. However, some alterations are not detected due to
      heterogeneity of biomarker expression inherent in these tumors, but this
      shortfall can be improved.

PMID- 20139053
TI  - Maternal acute lymphoctic leukemia with rearrangement of the mixed lineage
      leukemia gene occurring during pregnancy.
AB  - Acute lymphoblastic leukemia (ALL) is a relatively rare disease during pregnancy,
      accounting for about 15% of all cases of pregnancy-associated leukemia. Although
      mixed lineage leukemia gene (MLL) rearrangement is the dominant genetic
      aberration in infantile acute leukemia, the occurrence of MLL gene rearrangement
      in maternal ALL occurring during pregnancy has not been reported. Out of 31 cases
      of maternal leukemia diagnosed during pregnancy at our institution, 5 were ALL
      cases. Three of the 5 patients had MLL gene rearrangement. The data for these 5
      patients are presented in this report. We believe that the association of MLL
      gene rearrangement with maternal leukemia is biologically plausible and this
      observation needs to be validated in a larger cohort of pregnancy-associated
      maternal leukemia cases.

PMID- 20139054
TI  - Accuracy of the Fischer scoring system and the Breast Imaging Reporting and Data
      System in identification of malignant breast lesions.
AB  - BACKGROUND AND OBJECTIVES: Fischer developed a scoring system in 1999 that made
      identifying malignant lesions much easier for inexperienced radiologists. Our
      study was performed to assess whether this scoring system would help beginners to
      accurately diagnose breast lesions on magnetic resonance (MR) imaging and to
      assess the correlation between the magnetic resonance mammography Breast Imaging
      Reporting and Data System (MRM BI-RADS) grade and the final diagnosis. PATIENTS
      AND METHODS: The lesion morphology and contrast kinetics of 63 masses in 41
      patients were evaluated on MRI and accorded a MRM BI-RADS final assessment
      category using the Fischer scoring system. The accuracy was evaluated after the
      final diagnosis was obtained by tissue sampling and follow-up imaging. RESULTS:
      There were 25 malignant and 30 benign lesions. Eight lesions were seen by MRI
      only and we could not verify their pathology since we did not have MR-guided
      biopsy facilities at the time of the study. On MR mammography, the proven
      carcinomatous lesions were characterized as BI-RADS category V in 16 (64%),
      category IV in 7 (28%), and category III in 2 (8%) lesions. Benign lesions were
      graded as category V in 3 (10%), category IV in 6 (20%), and category III in 3
      (10%), category II in 10 (33%) and category I in 8 (27%) lesions. The MRM BI-RADS
      category accurately predicted malignancy in 92% and a benign pathology in 70% of
      the lesions. The overlap between the MRM features of chronic inflammatory lesions
      and carcinomas resulted in a lower accuracy in diagnosing benign as compared to
      malignant lesions. CONCLUSION: The MRM BI-RADS lexicon using the Fischer scoring
      system is useful and has a high predictive value, especially for malignant breast
      lesions, and is easy to apply. Overlapping features between benign inflammatory
      and malignant lesions might yield a reduced accuracy in inflammatory pathologies.

PMID- 20139055
TI  - The many faces of Ewing sarcoma: difficult to diagnose pediatric cases.
AB  - Ewing sarcoma (ES) is the second most frequent primary malignant bone cancer,
      following osteosarcoma. ES is a small round-cell tumor typically arising in the
      bones, rarely in soft tissues, of children and adolescents. We describe four
      children aged 3, 3.5, 9, and 9.5 years, who presented with two femur masses
      simultaneously (patient 1), a huge mediastinal mass (patient 2), an abdomino
      mediastinal mass with dysphagia (patient 3), and a huge abdomino-pelvic mass
      (patient 4). Our patients were of younger age and had abnormal presentations that
      made initial diagnosis difficult, but also are representative of the different
      problems encountered in pediatric practice. Biopsy initially revealed round cell
      tumor and by immunohistochemistry, CD99 was positive, which confirmed the
      diagnosis of ES. Our patients were difficult to diagnosis.The patients were
      misdiagnosed initially, so there was a delay in diagnosis. Definitive diagnosis
      required use of various radiological imaging methods and immunohistochemistry.

PMID- 20139056
TI  - Systemic amyloidosis presenting as mucocutaneous bullous lesions.
AB  - A 65-year-old male presented with hemorrhagic bullous skin lesions with purpura
      and ecchymoses. There was increased skin fragility with a strongly positive
      Nikolsky sign. Histopathology of the skin revealed large amounts of amyloid
      deposits in the dermis with a positive Congo Red staining around the dermal
      vessels. Examination and tests in this patient also revealed anemia,
      hepatomegaly, infiltrative cardiomyopathy, polyneuropathy and immunoglobulin l
      deposition, favoring a diagnosis of primary amyloidosis (AL type). The present
      case is reported in view of the rarity of the bullous variant of primary systemic
      amyloidosis as well as presence of mucosal lesions and a positive Nikolsky sign.

PMID- 20139057
TI  - Infantile hepatic hemangioendothelioma: an 8-month old infant successfully
      treated with a corticosteroid.
AB  - Infantile hemangioendothelioma is a rare benign vascular tumor of the liver. We
      report a case of hepatic hemangioendothelioma in an 8- month-old female infant
      who presented with hepatomegaly and respiratory distress, which was successfully
      treated with oral prednisolone for six months.

PMID- 20139058
TI  - Perivascular epithelioid cell tumor (PEComa) of the uterus with aggressive
      behavior at presentation.
AB  - Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor composed
      of histologically and immunohistochemically distinctive perivascular epithelioid
      cells (PECs). Both benign and malignant tumors have been identified, but the
      criteria for diagnosis of malignancy have not been fully established due to the
      rarity of the tumor. We report on a case of uterine PEComa in a 33-year old woman
      with lymph node metastasis at presentation. The tumor had the characteristic
      histologic features of PEComa with cytologic atypia, mitotic activity of 2/10
      high power field (HPF), and necrosis; it exhibited immunopositivity for HMB-45,
      calponin and desmin and was negative for melan-A. The patient received
      neoadjuvant chemotherapy, debulking surgery and adjuvant chemotherapy. No
      evidence of recurrence or metastasis was apparent 8 months after surgery.

PMID- 20139059
TI  - Spontaneous recovery of chylothorax caused by lymphoma.
AB  - Chylothorax is a rare complication with both traumatic and non-traumatic causes.
      The most common non-traumatic cause is malignancy, especially lymphoma. Lymph
      discharges into the pleural space, causing nutritional, metabolic, immunologic
      and respiratory complications. We evaluated the case of a patient suffering from
      a low-grade lymphoma who developed chylothorax that did not respond to
      chemotherapy and conservative treatment. This patient recovered spontaneously.

PMID- 20139060
TI  - Effect of urea on protein separation by ion-exchange chromatography.
AB  - Ion-exchange chromatography (IEC) is the most frequently used chromatographic
      technique for the separation of proteins and peptides. In this article, the
      effects of urea on IEC separation of kiwifruit actinidin, egg white and urinary
      proteins were examined. The purity and relative amount of each protein in
      different conditions (in the presence or absence of urea) were compared with each
      other. The three parameters, including resolution, selectivity and efficiency of
      column in the presence of urea, were calculated and compared with the absence of
      urea. The results revealed that urea improved the purity of proteins and the
      resolution, selectivity and efficiency of IEC in separation of studied proteins.

PMID- 20139061
TI  - Role of the G-protein and tyrosine kinase--Rho/ROK pathways in 15
      hydroxyeicosatetraenoic acid induced pulmonary vasoconstriction in hypoxic rats.
AB  - It has been previously reported by us that hypoxia activates lung 15-lipoxygenase
      (15-LO), which catalyzes arachidonic acid to 15-hydroxyeicosatetraenoic acid (15
      HETE), leading to the constriction of pulmonary artery (PA). Rho-associated
      serine/threonine kinase (ROK), a downstream effector of small GTPase RhoA that
      may be modulated by G-protein and tyrosine kinase, plays an important role in
      smooth muscle contraction. However, whether the 15-HETE induced PA
      vasoconstriction involves the Rho/ROK pathway remains to be demonstrated.
      Therefore, we studied the contribution of ROK as well as G-protein and tyrosine
      kinase to the 15-HETE induced pulmonary vasoconstriction using PA ring technique,
      RNA interference technology, RP-HPLC, western blot and RT-PCR combined with the
      blockers. The hypoxia-induced expression of ROK is regulated by 15-HETE in rat PA
      smooth muscle cells (PASMCs), leading to vasoconstriction. The up-regulation of
      ROK expression caused by 15-HETE appears to be mediated by the G-protein and
      tyrosine kinase pathways. The translocation of ROK2 from the nucleus to the
      cytoplasm during hypoxia exposure relies on the mechanism for 15-HETE production.
      These results suggest that 15-HETE may mediate the up-regulation of ROK
      expression through G-protein and tyrosine kinase pathways under hypoxic
      condition, leading to PA vasoconstriction.

PMID- 20139062
TI  - Expression and characterization of PKL01, an Ndr kinase homolog in Lotus
      japonicus.
AB  - We isolated cDNA clones for novel protein kinases by expression cloning from
      Lotus japonicus. The LNZ001, one of the isolated clones, encodes a protein of 547
      amino acids with a predicted molecular weight of 63,349. Since the protein
      contains 12 highly conserved subdomains specific to Ser/Thr protein kinases, we
      designated it PKL01. When homology searches based on the PKL01 sequence were
      carried out, the protein was found to show sequence homology with nuclear Dbf2
      related kinases (Ndr kinases). When PKL01 was produced using an Escherichia coli
      expression system and purified to homogeneity, it underwent intermolecular
      autophosphorylation. The major autophosphorylation site was identified as Ser-317
      by using various point mutants, and phosphorylation at this site was found to be
      critical for the kinase activity. PKL01 was found to be widely distributed in the
      leaves, stems, roots and root nodules by northern hybridization experiments. When
      endogenous substrates were screened using fractionated preparations from various
      parts of plants, PKL01 preferentially phosphorylated basic proteins in tissue
      extracts. These results suggest that PKL01 is an Ndr kinase homolog in L.
      japonicus and may be involved in the regulation of cellular functions through
      phosphorylation of basic protein substrates such as histones.

PMID- 20139063
TI  - Triptolide reduces cyst formation in a neonatal to adult transition Pkd1 model of
      ADPKD.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), a major cause
      of end-stage renal failure, results from genetic mutation of either polycystin-1
      (Pkd1) or polycystin-2 (Pkd2). In order to develop novel therapies to treat the
      advancement of disease progression, numerous rodent models of different genetic
      backgrounds are available to study cyst development. METHODS: Here, a Pkd1-floxed
      inducible mouse model using the interferon responsive Mx1Cre-recombinase was
      utilized to test the effect of the small molecule triptolide. Relative to other
      Pkd1 inactivation models, cyst progression in this neonatal to adult transition
      model is attenuated. Following the characterization of inducible cyst formation
      in these mice, the development of kidney cysts from triptolide or vehicle-treated
      animals was analysed. RESULTS: Although Pkd1 deletion on postnatal Days P10 and
      P12 resulted in numerous cysts by P35, daily injections with triptolide beginning
      on Day P16 significantly reduced the total number of cysts per kidney, with a
      pronounced effect on the number of microcysts and the overall cystic burden.
      Additionally, renal function as assessed by blood urea nitrogen levels was also
      improved in triptolide-treated mice at both the P22 and P35 time points. As the
      Pkd1(flox/flox);Mx1Cre model has not been previously used for drug development
      studies, the feasibility of a 6-month adult Pkd1 inactivation study was also
      tested. While kidney cyst formation was minimal and focal in nature, livers of
      these Pkd1-deficient mice were severely cystic, enlarged and pale. CONCLUSIONS:
      These results suggest that the Pkd1(flox/flox);Mx1Cre model of ADPKD is amenable
      to short-term kidney cyst formation drug studies; however, it may be problematic
      for long-term therapeutic research where widespread liver cysts and fibrosis
      could compromise drug metabolism.

PMID- 20139064
TI  - Combined liver-kidney transplantation in patients with cirrhosis and chronic
      kidney disease.
AB  - The outcome of patients with cirrhosis and chronic kidney disease treated with
      combined liver-kidney transplantation (CLKT) is not well known because most
      series of patients treated with CLKT include not only patients with cirrhosis but
      also patients with inherited diseases without cirrhosis. To evaluate to what
      extent the combined kidney transplantation impairs posttransplantation outcome
      compared to liver transplantation (LT) alone, the outcome of patients with
      cirrhosis and chronic kidney disease treated with CLKT (n = 20) was compared to
      that of a group of patients with cirrhosis without chronic kidney disease treated
      with LT alone matched by age, sex, year of transplantation and severity of
      cirrhosis (n = 60). The primary end point of the study was survival, and
      secondary end points were outcome of renal function and complications within 6
      months of transplantation. Patients with CLKT had a higher incidence of bacterial
      infections and transfusion requirements compared to LT patients. The incidence of
      acute renal failure during the first 6 months was similar, yet the severity of
      renal failure was greater in patients with CLKT. Hospital and intensive care unit
      (ICU) stays were longer in the CLKT group. One- and three-year survival
      probabilities in patients treated with CLKT were 80 and 75% compared to 97 and
      88%, respectively, in patients treated with LT. In conclusion, CLKT for patients
      with cirrhosis and chronic kidney disease is associated with a relatively high
      frequency of postoperative complications that moderately impairs short-term
      survival. However, 3-year survival of patients with cirrhosis treated with CLKT
      is excellent.

PMID- 20139065
TI  - Impact of peritoneal transport characteristics on cardiac function in paediatric
      peritoneal dialysis patients: a Turkish Pediatric Peritoneal Dialysis Study Group
      (TUPEPD) report.
AB  - BACKGROUND: The peritoneal equilibration test (PET) is recommended in paediatric
      peritoneal dialysis (PD) patients to assist prescription management. Despite
      contradictory reports, high transporter status is associated with reduced
      survival rate in adults. Since cardiac disease is one of the main causes of
      mortality in paediatric PD patients, we aimed to evaluate whether transport
      features have any effect on biochemical data and cardiac function in this group.
      METHODS: One hundred and ten PD patients (13 +/- 5 years, PD vintage: 31 +/- 27
      months) were enrolled into the study. Four-hour dialysate/plasma creatinine ratio
      was used for differentiating PET groups. Thirty-eight patients were high
      transporters, 29 were high-average transporters and 43 were low-average/low
      transporters. Echocardiography was performed in all subjects. RESULTS: Age, PD
      vintage, dialysate glucose concentration, ultrafiltration volume, urine volume
      and blood pressure levels were similar in all PET groups. No biochemical or
      echocardiographic data (ejection fraction, fractional shortening, left
      ventricular mass index, myocardial performance index, power Doppler E/tissue
      Doppler E ratio reflecting diastolic function) were different among PET groups
      except lower albumin (P = 0.025) levels in high transporters and higher high
      sensitivity C-reactive protein (P = 0.026) levels in high and high-average
      transporters compared to other transport groups. CONCLUSIONS: Cardiac structural
      and functional abnormalities are highly prevalent among paediatric PD patients.
      Transport rates did not have a significant effect on biochemical parameters or
      cardiac structural/functional parameters. It might be suggested that being a high
      transporter does not provide a disadvantage in terms of atherogenic tendency and
      cardiac disease in paediatric PD patients. Oligoanuria, anaemia and hypertension
      were independent predictors of cardiac disease.

PMID- 20139066
TI  - Statistical methods for the assessment of prognostic biomarkers (Part I):
      discrimination.

PMID- 20139067
TI  - Isopeptide bonds block the mechanical extension of pili in pathogenic
      Streptococcus pyogenes.
AB  - In the early stages of an infection, pathogenic bacteria use long fibrous
      structures known as pili as adhesive anchors for attachment to the host cells.
      These structures also play key roles in colony and biofilm formation. In all
      those processes, pili must withstand large mechanical forces. The pili of the
      nasty gram-positive human pathogen Streptococcus pyogenes are assembled as
      single, micrometer long tandem modular proteins of covalently linked repeats of
      pilin proteins. Here we use single molecule force spectroscopy techniques to
      study the mechanical properties of the major pilin Spy0128. In our studies, we
      engineer polyproteins containing repeats of Spy0128 flanked by the well
      characterized I27 protein which provides an unambiguous mechanical fingerprint.
      We find that Spy0128 is an inextensible protein, even when pulled at forces of up
      to 800 pN. We also found that this remarkable mechanical resilience, unique among
      the modular proteins studied to date, results from the strategically located
      intramolecular isopeptide bonds recently identified in the x-ray structure of
      Spy0128. Removal of the isopeptide bonds by mutagenesis readily allowed Spy0128
      domains to unfold and extend, albeit at relatively high forces of 172 pN (N
      terminal domain) or 250 pN (C-terminal domain). Our results show that in contrast
      to the elastic roles played by large tandem modular proteins such as titin and
      fibronectin, the giant pili of S. pyogenes evolved to abrogate mechanical
      extensibility, a property that may be crucial in the pathogenesis of this most
      virulent bacterium and, therefore, become the target of new therapeutic
      approaches against its infections.

PMID- 20139068
TI  - Generation of human induced pluripotent stem cells from umbilical cord matrix and
      amniotic membrane mesenchymal cells.
AB  - The umbilical cord and placenta are extra-embryonic tissues of particular
      interest for regenerative medicine. They share an early developmental origin and
      are a source of vast amounts of cells with multilineage differentiation potential
      that are poorly immunogenic and without controversy. Moreover, these cells are
      likely exempt from incorporated mutations when compared with juvenile or adult
      donor cells such as skin fibroblasts or keratinocytes. Here we report the
      efficient generation of induced pluripotent stem cells (iPSCs) from mesenchymal
      cells of the umbilical cord matrix (up to 0.4% of the cells became reprogrammed)
      and the placental amniotic membrane (up to 0.1%) using exogenous factors and a
      chemical mixture. iPSCs from these 2 tissues homogeneously showed human embryonic
      stem cell (hESC)-like characteristics including morphology, positive staining for
      alkaline phosphatase, normal karyotype, and expression of hESC-like markers
      including Nanog, Rex1, Oct4, TRA-1-60, TRA-1-80, SSEA-3, and SSEA-4. Selected
      clones also formed embryonic bodies and teratomas containing derivatives of the 3
      germ layers, and could as well be readily differentiated into functional motor
      neurons. Among other things, our cell lines may prove useful for comparisons
      between iPSCs derived from multiple tissues regarding the extent of the
      epigenetic reprogramming, differentiation ability, stability of the resulting
      lineages, and the risk of associated abnormalities.

PMID- 20139069
TI  - FKBP38 protects Bcl-2 from caspase-dependent degradation.
AB  - The cellular processes that regulate Bcl-2 at the posttranslational levels are as
      important as those that regulate bcl-2 synthesis. Previously we demonstrated that
      the suppression of FK506-binding protein 38 (FKBP38) contributes to the
      instability of Bcl-2 or leaves Bcl-2 unprotected from degradation in an unknown
      mechanism. Here, we studied the underlying molecular mechanism mediating this
      process. We first showed that Bcl-2 binding-defective mutants of FKBP38 fail to
      accumulate Bcl-2 protein. We demonstrated that the FKBP38-mediated Bcl-2
      stability is specific as the levels of other anti-apoptotic proteins such as Bcl
      X(L) and Mcl-1 remained unaffected. FKBP38 enhanced the Bcl-2 stability under the
      blockade of de novo protein synthesis, indicating it is posttranslational. We
      showed that the overexpression of FKBP38 attenuates reduction rate of Bcl-2, thus
      resulting in an increment of the intracellular Bcl-2 level, contributing to the
      resistance of apoptotic cell death induced by the treatment of kinetin riboside,
      an anticancer drug. Caspase inhibitors markedly induced the accumulation of Bcl
      2. In caspase-3-activated cells, the knockdown of endogenous FKBP38 by small
      interfering RNA resulted in Bcl-2 down-regulation as well, which was
      significantly recovered by the treatment with caspase inhibitors or
      overexpression of FKBP38. Finally we presented that the Bcl-2 cleavage by caspase
      3 is blocked when Bcl-2 binds to FKBP38 through the flexible loop. Taken
      together, these results suggest that FKBP38 is a key player in regulating the
      function of Bcl-2 by antagonizing caspase-dependent degradation through the
      direct interaction with the flexible loop domain of Bcl-2, which contains the
      caspase cleavage site.

PMID- 20139070
TI  - Kidney-specific overexpression of Sirt1 protects against acute kidney injury by
      retaining peroxisome function.
AB  - Sirt1, a NAD-dependent protein deacetylase, is reported to regulate intracellular
      metabolism and attenuate reactive oxidative species (ROS)-induced apoptosis
      leading to longevity and acute stress resistance. We created transgenic (TG) mice
      with kidney-specific overexpression of Sirt1 using the promoter sodium-phosphate
      cotransporter IIa (Npt2) driven specifically in proximal tubules and investigated
      the kidney-specific role of Sirt1 in the protection against acute kidney injury
      (AKI). We also elucidated the role of number or function of peroxisome and
      mitochondria in mediating the mechanisms for renal protective effects of Sirt1 in
      AKI. Cisplatin-induced AKI decreased the number and function of peroxisomes as
      well as mitochondria and led to increased local levels of ROS production and
      renal tubular apoptotic cells. TG mice treated with cisplatin mitigated AKI,
      local ROS, and renal tubular apoptotic tubular cells. Consistent with these
      results, TG mice treated with cisplatin also exhibited recovery of peroxisome
      number and function, as well as rescued mitochondrial function; however,
      mitochondrial number was not recovered. Immunoelectron microscopic findings
      consistently demonstrated that the decrease in peroxisome number by cisplatin in
      wild type mice was restored in transgenic mice. In HK-2 cells, a cultured
      proximal tubule cell line, overexpression of Sirt1 rescued the cisplatin-induced
      cell apoptosis through the restoration of peroxisome number, although the
      mitochondria number was not restored. These results indicate that Sirt1
      overexpression in proximal tubules rescues cisplatin-induced AKI by maintaining
      peroxisomes number and function, concomitant up-regulation of catalase, and
      elimination of renal ROS levels. Renal Sirt1 can be a potential therapeutic
      target for the treatment of AKI.

PMID- 20139071
TI  - Cul8/Rtt101 forms a variety of protein complexes that regulate DNA damage
      response and transcriptional silencing.
AB  - The budding yeast, Saccharomyces cerevisiae, has three cullin proteins, which act
      as platforms for Cullin-based E3 ubiquitin ligases. Genetic evidence indicates
      that Cul8, together with Mms1, Mms22, and Esc4, is involved in the repair of DNA
      damage that can occur during DNA replication. Cul8 is thought to form a complex
      with these proteins, but the composition and the function of Cul8-based E3
      ubiquitin ligases remain largely uncharacterized. Herein, we report a
      comprehensive biochemical analysis of Cul8 complexes. Cul8 was found to form a
      Cul8-Mms1-Mms22-Esc4 complex under physiological conditions, with Mms1 bridging
      Cul8 and Mms22 and Mms22 bridging Mms1 and Esc4. Domain analysis demonstrated
      that the N-terminal region of Mms1 and the C-terminal region of Mms22 are
      required for the Mms1-Mms22 interaction, whereas the N-terminal region of Mms22
      is required for the Mms22-Esc4 interaction. We also found other Cul8-Mms1-binding
      proteins Ctf4, Esc2, and Orc5 using yeast two-hybrid screening. Esc4 and Ctf4
      bound to Mms22 directly and bound to Cul8-Mms1 in the presence of Mms22, whereas
      Esc2 and Orc5 interacted with both Cul8 and Mms1, independently. We found that
      Cul8, Mms1, and Mms22 participated in the regulation of transcriptional silencing
      of yeast telomeres. These results suggest that Cul8-Mms1, as part of various
      protein complexes, is involved in the regulation of chromatin metabolism.

PMID- 20139072
TI  - Unfolding of metastable linker region is at the core of Hsp33 activation as a
      redox-regulated chaperone.
AB  - Hsp33, a molecular chaperone specifically activated by oxidative stress
      conditions that lead to protein unfolding, protects cells against oxidative
      protein aggregation. Stress sensing in Hsp33 occurs via its C-terminal redox
      switch domain, which consists of a zinc center that responds to the presence of
      oxidants and an adjacent metastable linker region, which responds to unfolding
      conditions. Here we show that single mutations in the N terminus of Hsp33 are
      sufficient to either partially (Hsp33-M172S) or completely (Hsp33-Y12E) abolish
      this post-translational regulation of Hsp33 chaperone function. Both mutations
      appear to work predominantly via the destabilization of the Hsp33 linker region
      without affecting zinc coordination, redox sensitivity, or substrate binding of
      Hsp33. We found that the M172S substitution causes moderate destabilization of
      the Hsp33 linker region, which seems sufficient to convert the redox-regulated
      Hsp33 into a temperature-controlled chaperone. The Y12E mutation leads to the
      constitutive unfolding of the Hsp33 linker region thereby turning Hsp33 into a
      constitutively active chaperone. These results demonstrate that the redox
      controlled unfolding of the Hsp33 linker region plays the central role in the
      activation process of Hsp33. The zinc center of Hsp33 appears to act as the redox
      sensitive toggle that adjusts the thermostability of the linker region to the
      cell redox status. In vivo studies confirmed that even mild overexpression of the
      Hsp33-Y12E mutant protein inhibits bacterial growth, providing important evidence
      that the tight functional regulation of Hsp33 chaperone activity plays a vital
      role in bacterial survival.

PMID- 20139073
TI  - Insulin-like growth factor-1 (IGF-1)-induced processing of amyloid-beta precursor
      protein (APP) and APP-like protein 2 is mediated by different metalloproteinases.
AB  - alpha-Secretase cleavage of the amyloid precursor protein (APP) is of great
      interest because it prevents the formation of the Alzheimer-linked amyloid-beta
      peptide. APP belongs to a conserved gene family including the two paralogues APP
      like protein (APLP) 1 and 2. Insulin-like growth factor-1 (IGF-1) stimulates the
      shedding of all three proteins. IGF-1-induced shedding of both APP and APLP1 is
      dependent on phosphatidylinositol 3-kinase (PI3-K), whereas APLP2 shedding is
      independent of this signaling pathway. Here, we used human neuroblastoma SH-SY5Y
      cells to investigate the involvement of protein kinase C (PKC) in the proteolytic
      processing of endogenously expressed members of the APP family. Processing was
      induced by IGF-1 or retinoic acid, another known stimulator of APP alpha
      secretase shedding. Our results show that stimulation of APP and APLP1 processing
      involves multiple signaling pathways, whereas APLP2 processing is mainly
      dependent on PKC. Next, we wanted to investigate whether the difference in the
      regulation of APLP2 shedding compared with APP shedding could be due to
      involvement of different processing enzymes. We focused on the two major alpha
      secretase candidates ADAM10 and TACE, which both are members of the ADAM (a
      disintegrin and metalloprotease) family. Shedding was analyzed in the presence of
      the ADAM10 inhibitor GI254023X, or after transfection with small interfering RNAs
      targeted against TACE. The results clearly demonstrate that different alpha
      secretases are involved in IGF-1-induced processing. APP is mainly cleaved by
      ADAM10, whereas APLP2 processing is mediated by TACE. Finally, we also show that
      IGF-1 induces PKC-dependent phosphorylation of TACE.

PMID- 20139074
TI  - Metallothionein-1 isoforms and vimentin are direct PU.1 downstream target genes
      in leukemia cells.
AB  - PU.1 is a key transcription factor for hematopoiesis and plays important roles in
      various hematological malignancies. To clarify the molecular function of PU.1, we
      initially tried to identify bona fide target genes regulated by PU.1. Dual
      microarrays were employed for this study to compare PU.1-knockdown K562 cells
      (K562PU.1KD) stably expressing PU.1 short inhibitory RNAs versus control cells
      and PU.1-overexpressing K562 cells (K562PU.1OE) versus control cells. In these
      analyses, we found that several genes, including metallothionein (MT)-1 isoforms
      (MT-1G and MT-1A) and vimentin (VIM), were markedly induced while Jun
      dimerization protein (JDP) 2 was suppressed in K562PU.1KD cells. Furthermore, the
      mRNA expressions of the MT-1 and VIM genes were inversely correlated and the mRNA
      expression of JDP2 was positively correlated with PU.1 mRNA expression in 43
      primary acute myeloid leukemia specimens (MT-1G: R = -0.50, p < 0.001; MT-1A: R =
      -0.58, p < 0.0005; VIM: R = -0.39, p < 0.01; and JDP2: R = 0.30, p < 0.05). Next,
      we analyzed the regulation of the MT-1 and VIM genes. We observed increased
      associations of acetylated histones H3 and H4 with the promoters of these genes
      in K562PU.1KD cells. Sequence analyses of the regions approximately 1 kb upstream
      from the transcription start sites of these genes revealed numerous CpG sites,
      which are potential targets for DNA methylation. Chromatin immunoprecipitation
      assays revealed that methyl CpG-binding protein 2 (MeCP2) and PU.1 bound to the
      CpG-rich regions in the MT-1 and VIM promoters. Bisulfite sequencing analyses of
      the PU.1-bound regions of these promoters revealed that the proportions of
      methylated CpG sites were tightly related to the PU.1 expression levels.

PMID- 20139075
TI  - Ubiquitin ligase cullin 7 induces epithelial-mesenchymal transition in human
      choriocarcinoma cells.
AB  - Germ line mutations of the ubiquitin ligase cullin 7 (CUL7) are linked to 3-M
      syndrome and Yakuts short stature syndrome, both of which are characterized by
      pre- and post-natal growth retardation. CUL7 knock-out mice show placental and
      embryonic defects similar to intrauterine growth retardation, suggesting a role
      of CUL7 in placentation. CUL7 was found in this study to be highly expressed in
      first trimester invasive human placental villi as well as in HTR8/SVneo and
      B6Tert cells, two cell lines derived from human first trimester trophoblast
      cells. However, CUL7 levels in term trophoblast cells or JEG-3 cells, which are
      derived from human choriocarcinoma but exhibit weak invasion capacity, were low
      or undetectable. Forced expression of CUL7 in JEG-3 cells induced cell
      morphological changes characteristic of epithelial-mesenchymal transition, which
      was accompanied by a complete loss of the epithelial markers E-cadherin and P
      cadherin and a significant elevation of mesenchymal markers Vimentin and N
      cadherin. JEG-3 cells expressing CUL7 exhibited enhanced cell migration and
      invasion. Conversely, CUL7-specific RNA interference in HTR8/SVneo cells resulted
      in increased E-cadherin expression and reduced cell migration and invasion.
      Furthermore, CUL7 expression down-regulated E-cadherin mRNA expression by up
      regulating ZEB1 and Slug, two transcriptional repressors of E-cadherin. Finally,
      CUL7-induced loss of E-cadherin expression was partially reversed by treatment of
      CUL7-expressing cells with the proteasome inhibitor MG-132. These results suggest
      that the CUL7 E3 ligase is a key regulator in trophoblast cell epithelial
      mesenchymal transition and placental development.

PMID- 20139076
TI  - Two-color photoactivatable probe for selective tracking of proteins and cells.
AB  - We report the development and application of photoactivatable Green Cherry
      (G(PA)C), the first genetically encoded "continuously red-photoactivatable green"
      two-color probe for live cell imaging. G(PA)C is unique in that it enables real
      time tracking of selected subpopulations of proteins and organelles in the cell
      or of cells within tissues and whole organisms, with constant reference to the
      entire population of the probe. Using G(PA)C-zyxin as proof of utility, we
      obtained new insights into the dynamic movement of the cytoskeletal protein
      zyxin. We show that zyxin is continuously and rapidly recruited from the cytosol
      into established focal adhesions. It can also move rapidly within a given focal
      adhesion and "hop" between adjacent focal adhesions, emphasizing the dynamic
      nature of proteins within these structures. The in vivo utility of G(PA)C is
      exemplified by tracking hemocyte movements using a versatile transgenic
      Drosophila model engineered to express G(PA)C in tissues and cells of interest
      under the control of the GAL4-inducible promoter.

PMID- 20139077
TI  - Transcriptional regulation of p21/CIP1 cell cycle inhibitor by PDEF controls cell
      proliferation and mammary tumor progression.
AB  - The Ets family of transcription factors control a myriad of cellular processes
      and contribute to the underlying genetic loss of cellular homeostasis resulting
      in cancer. PDEF (prostate-derived Ets factor) has been under investigation for
      its role in tumor development and progression. However, the role of PDEF in
      cancer development has been controversial. Some reports link PDEF to tumor
      promoter, and others show tumor-suppressing functions in various systems under
      different conditions. So far, there has been no conclusive evidence from in vivo
      experiments to prove the role of PDEF. We have used both in vitro and in vivo
      systems to provide a conclusive role of PDEF in the progression process. PDEF
      expressing cells block the cell growth rate, and this retardation was reversible
      when PDEF expression was silenced with PDEF-specific small interfering RNA. When
      these PDEF-expressing cells were orthotopically implanted into the mouse mammary
      gland, tumor incidence and growth rate were significantly retarded. Cell cycle
      analysis revealed that PDEF expression partially blocked cell cycle progression
      at G(1)/S without an effect on apoptosis. PDEF overexpression resulted in an
      increase in p21/CIP1 at both the mRNA and protein levels, resulting in decreased
      Cdk2 activity. Promoter deletion analysis, electrophoresis mobility shift assays,
      and chromatin immunoprecipitation studies identified the functional Ets DNA
      binding site at -2118 bp of the p21/CIP1 gene promoter. This site is capable of
      binding and responding to PDEF. Furthermore, we silenced p21/CIP1 expression in
      PDEF-overexpressing cells by small interfering RNA. p21-silenced PDEF cells
      exhibited significantly increased cell growth in vitro and in vivo, demonstrating
      the p21 regulation by PDEF as a key player. These experiments identified PDEF as
      a new transcription factor that directly regulates p21/CIP1 expression under non
      stressed conditions. This study conclusively proves that PDEF is a breast tumor
      suppressor for the first time using both in vitro and in vivo systems. PDEF can
      be further developed as a target for designing therapeutic intervention of breast
      cancer.

PMID- 20139078
TI  - Structure-function study of the N-terminal domain of exocyst subunit Sec3.
AB  - The exocyst is an evolutionarily conserved octameric complex involved in
      polarized exocytosis from yeast to humans. The Sec3 subunit of the exocyst acts
      as a spatial landmark for exocytosis through its ability to bind phospholipids
      and small GTPases. The structure of the N-terminal domain of Sec3 (Sec3N) was
      determined ab initio and defines a new subclass of pleckstrin homology (PH)
      domains along with a new family of proteins carrying this domain. Respectively, N
      and C-terminal to the PH domain Sec3N presents an additional alpha-helix and two
      beta-strands that mediate dimerization through domain swapping. The structure
      identifies residues responsible for phospholipid binding, which when mutated in
      cells impair the localization of exocyst components at the plasma membrane and
      lead to defects in exocytosis. Through its ability to bind the small GTPase Cdc42
      and phospholipids, the PH domain of Sec3 functions as a coincidence detector at
      the plasma membrane.

PMID- 20139079
TI  - Critical requirement of GABPalpha for normal T cell development.
AB  - GA binding protein (GABP) consists of GABPalpha and GABPbeta subunits. GABPalpha
      is a member of Ets family transcription factors and binds DNA via its conserved
      Ets domain, whereas GABPbeta does not bind DNA but possesses transactivation
      activity. In T cells, GABP has been demonstrated to regulate the gene expression
      of interleukin-7 receptor alpha chain (IL-7Ralpha) and postulated to be critical
      in T cell development. To directly investigate its function in early thymocyte
      development, we used GABPalpha conditional knock-out mice where the exons
      encoding the Ets DNA-binding domain are flanked with LoxP sites. Ablation of
      GABPalpha with the Lck-Cre transgene greatly diminished thymic cellularity,
      blocked thymocyte development at the double negative 3 (DN3) stage, and resulted
      in reduced expression of T cell receptor (TCR) beta chain in DN4 thymocytes. By
      chromatin immunoprecipitation, we demonstrated in DN thymocytes that GABPalpha is
      associated with transcription initiation sites of genes encoding key molecules in
      TCR rearrangements. Among these GABP-associated genes, knockdown of GABPalpha
      expression by RNA interference diminished expression of DNA ligase IV, Artemis,
      and Ku80 components in DNA-dependent protein kinase complex. Interestingly,
      forced expression of prearranged TCR but not IL-7Ralpha can alleviate the DN3
      block in GABPalpha-targeted mice. Our observations collectively indicate that in
      addition to regulating IL-7Ralpha expression, GABP is critically required for TCR
      rearrangements and hence normal T cell development.

PMID- 20139080
TI  - Switch action of troponin on muscle thin filament as revealed by spin labeling
      and pulsed EPR.
AB  - We have used pulsed electron-electron double resonance (PELDOR) spectroscopy to
      measure the distance between spin labels at Cys(133) of the regulatory region of
      TnI (TnI133) and a native or genetically substituted cysteine of TnC (TnC44,
      TnC61, or TnC98). In the +Ca(2+) state, the TnC44-TnI133-T distance was 42 A,
      with a narrow distribution (half-width of 9 A), suggesting that the regulatory
      region binds the N-lobe of TnC. Distances for TnC61-TnI133 and TnC98-TnI133 were
      also determined to be 38 A (width of 12 A) and 22 A (width of 3.4 A),
      respectively. These values were all consistent with recently published crystal
      structure (Vinogradova, M. V., Stone, D. B., Malanina, G. G., Karatzaferi, C.,
      Cooke, R., Mendelson, R. A., and Fletterick, R. J. (2005) Proc. Natl Acad. Sci.
      U.S.A. 102, 5038-5043). Similar distances were obtained with the same spin pairs
      on a reconstituted thin filament in the +Ca(2+) state. In the -Ca(2+) state, the
      distances displayed broad distributions, suggesting that the regulatory region of
      TnI was physically released from the N-lobe of TnC and consequently fluctuated
      over a variety of distances on a large scale (20-80 A). The interspin distance
      appeared longer on the filament than on troponin alone, consistent with the
      ability of the region to bind actin. These results support a concept that the
      regulatory region of TnI, as a molecular switch, binds to the exposed hydrophobic
      patch of TnC and traps the inhibitory region of TnI away from actin in Ca(2+)
      activation of muscle.

PMID- 20139081
TI  - A fused alpha-beta "mini-spectrin" mimics the intact erythrocyte spectrin head-to
      head tetramer.
AB  - Head-to-head assembly of two spectrin heterodimers to form an actin-cross-linking
      tetramer is a physiologically dynamic interaction that contributes to red cell
      membrane integrity. Recombinant beta-spectrin C-terminal and alpha-spectrin N
      terminal peptides can form tetramer-like univalent complexes, but they cannot
      evaluate effects of the open-closed dimer interactions or lateral associations of
      the two-spectrin strands on tetramer formation. In this study we produced and
      characterized a fused "mini-spectrin dimer" containing the beta-spectrin C
      terminal region linked to the alpha-spectrin N-terminal region. This fused mini
      spectrin mimics structural and functional properties of intact, full-length
      dimers and tetramers, including lateral association of the alpha and beta
      subunits in the dimer and formation of a closed dimer. High performance liquid
      chromatography gel filtration analyses of this mini-spectrin provide the first
      direct non-imaging experimental evidence for open and closed spectrin dimers and
      show that dimer-tetramer-oligomer interconversion is slow at low temperatures and
      accelerated at 30 degrees C, analogous to full-length spectrin. This protein
      exhibits wild type dimer-tetramer dissociation constants of approximately 1 mum
      at 30 degrees C, independent of initial oligomeric state. Conformational states
      of the mini-spectrin dimer were probed further using chemical cross-linking,
      which identified distinct groups of cross-links for "open" and "closed" dimers
      and confirmed the N-terminal region of alpha-spectrin remains highly flexible in
      the complex, exhibiting closely analogous structures to those observed for the
      isolated alpha-spectrin N-terminal using NMR (Park, S., Caffrey, M. S., Johnson,
      M. E., and Fung, L. W. (2003) J. Biol. Chem. 278, 21837-21844). This fusion
      protein should serve as a useful template for structural and functional studies
      of the divalent tetramer site.

PMID- 20139082
TI  - Kinetic evaluation of cell membrane hydrolysis during apoptosis by human isoforms
      of secretory phospholipase A2.
AB  - Some isoforms of secretory phospholipase A(2) (sPLA(2)) distinguish between
      healthy and damaged or apoptotic cells. This distinction reflects differences in
      membrane physical properties. Because various sPLA(2) isoforms respond
      differently to properties of artificial membranes such as surface charge, they
      should also behave differently as these properties evolve during a dynamic
      physiological process such as apoptosis. To test this idea, S49 lymphoma cell
      death was induced by glucocorticoid (6-48 h) or calcium ionophore. Rates of
      membrane hydrolysis catalyzed by various concentrations of snake venom and human
      groups IIa, V, and X sPLA(2) were compared after each treatment condition. The
      data were analyzed using a model that evaluates the adsorption of enzyme to the
      membrane surface and subsequent binding of substrate to the active site. Results
      were compared temporally to changes in membrane biophysics and composition. Under
      control conditions, membrane hydrolysis was confined to the few unhealthy cells
      present in each sample. Increased hydrolysis during apoptosis and necrosis
      appeared to reflect substrate access to adsorbed enzyme for the snake venom and
      group X isoforms corresponding to weakened lipid-lipid interactions in the
      membrane. In contrast, apoptosis promoted initial adsorption of human groups V
      and IIa concurrent with phosphatidylserine exposure on the membrane surface.
      However, this observation was inadequate to explain the behavior of the groups V
      and IIa enzymes toward necrotic cells where hydrolysis was reduced or absent.
      Thus, a combination of changes in cell membrane properties during apoptosis and
      necrosis capacitates the cell for hydrolysis differently by each isoform.

PMID- 20139083
TI  - Metabolomic changes accompanying transformation and acquisition of metastatic
      potential in a syngeneic mouse mammary tumor model.
AB  - Breast cancer is the most common cancer type for women in the western world.
      Despite decades of research, the molecular processes associated with breast
      cancer progression are still inadequately defined. Here, we focus on the
      systematic alteration of metabolism by using the state of the art metabolomic
      profiling techniques to investigate the changes of 157 metabolites during the
      progression of normal mouse mammary epithelial cells to an isogenic series of
      mammary tumor cell lines with increasing metastatic potentials. Our results
      suggest a two-step metabolic progression hypothesis during the acquisition of
      tumorigenic and metastatic abilities. Metabolite changes accompanying tumor
      progression are identified in the intracellular and secreted forms in several
      pathways, including glycolysis, the tricarboxylic acid cycle, the pentose
      phosphate pathway, fatty acid and nucleotide biosynthesis, and the GSH-dependent
      antioxidative pathway. These results suggest possible biomarkers of breast cancer
      progression as well as opportunities of interrupting tumor progression through
      the targeting of metabolic pathways.

PMID- 20139084
TI  - Down-regulation of MyoD by calpain 3 promotes generation of reserve cells in
      C2C12 myoblasts.
AB  - Calpain 3 is a calcium-dependent cysteine protease that is primarily expressed in
      skeletal muscle and is implicated in limb girdle muscular dystrophy type 2A. To
      date, its best characterized function is located within the sarcomere, but this
      protease is found in other cellular compartments, which suggests that it exerts
      multiple roles. Here, we present evidence that calpain 3 is involved in the
      myogenic differentiation process. In the course of in vitro culture of myoblasts
      to fully differentiated myotubes, a population of quiescent undifferentiated
      "reserve cells" are maintained. These reserve cells are closely related to
      satellite cells responsible for adult muscle regeneration. In the present work,
      we observe that reserve cells express higher levels of endogenous Capn3 mRNA than
      proliferating myoblasts. We show that calpain 3 participates in the establishment
      of the pool of reserve cells by decreasing the transcriptional activity of the
      key myogenic regulator MyoD via proteolysis independently of the ubiquitin
      proteasome degradation pathway. Our results identify calpain 3 as a potential new
      player in the muscular regeneration process by promoting renewal of the satellite
      cell compartment.

PMID- 20139085
TI  - Suprastructures and dynamic properties of Mycobacterium tuberculosis FtsZ.
AB  - Tuberculosis causes the most death in humans by any bacterium. Drug targeting of
      bacterial cytoskeletal proteins requires detailed knowledge of the various
      filamentous suprastructures and dynamic properties. Here, we have investigated by
      high resolution electron microscopy the assembly of cell division protein and
      microtubule homolog FtsZ from Mycobacterium tuberculosis (MtbFtsZ) in vitro in
      the presence of various monovalent salts, crowding agents and polycations.
      Supramolecular structures, including two-dimensional rings, three-dimensional
      toroids, and multistranded helices formed in the presence of molecular crowding,
      were similar to those observed by fluorescence microscopy in bacteria in vivo.
      Dynamic properties of MtbFtsZ filaments were visualized by light scattering and
      real time total internal reflection fluorescence microscopy. Interestingly,
      MtbFtsZ revealed a form of dynamic instability at steady state. Cation-induced
      condensation phenomena of bacterial cytomotive polymers have not been
      investigated in any detail, although it is known that many bacteria can contain
      high amounts of polycations, which may modulate the prokaryotic cytoskeleton. We
      find that above a threshold concentration of polycations which varied with the
      valence of the cation, ionic strength, and pH, MtbFtsZ mainly formed sheets. The
      general features of these cation-induced condensation phenomena could be
      explained in the framework of the Manning condensation theory. Chirality and
      packing defects limited the dimensions of sheets and toroids at steady state as
      predicted by theoretical models. In first approximation simple physical
      principles seem to govern the formation of MtbFtsZ suprastructures.

PMID- 20139086
TI  - Identification of specific lipid-binding sites in integral membrane proteins.
AB  - Protein-lipid interactions are increasingly recognized as central to the
      structure and function of membrane proteins. However, with the exception of
      simplified models, specific protein-lipid interactions are particularly difficult
      to highlight experimentally. Here, we used molecular dynamics simulations to
      identify a specific protein-lipid interaction in lactose permease, a prototypical
      model for transmembrane proteins. The interactions can be correlated with the
      functional dependence of the protein to specific lipid species. The technique is
      simple and widely applicable to other membrane proteins, and a variety of lipid
      matrices can be used.

PMID- 20139087
TI  - Genetic dissection of a mitochondria-vacuole signaling pathway in yeast reveals a
      link between chronic oxidative stress and vacuolar iron transport.
AB  - Deletion of two homologous genes, MRS3 and MRS4, that encode mitochondrial iron
      transporters affects the activity of the vacuolar iron importer Ccc1. Ccc1 levels
      are decreased in Deltamrs3Deltamrs4 cells, but the activity of the transporter is
      increased, resulting is reduced cytosolic iron. Overexpression of CCC1 in
      Deltamrs3Deltamrs4 cells results in a severe growth defect due to decreased
      cytosolic iron, referred to as the mitochondria-vacuole signaling (MVS)
      phenotype. Mutants were identified that suppress the MVS growth defect, and FRA1
      was identified as a gene that suppresses the MVS phenotype. Overexpression of
      FRA1 suppresses altered transition metal metabolism in Deltamrs3Deltamrs4 cells,
      whereas deletion of FRA1 is synthetically lethal with Deltamrs3Deltamrs4. Fra1
      binds to Tsa1, which encodes a thioredoxin-dependent peroxidase. Deletion of TSA1
      or TRR1 is synthetically lethal in Deltamrs3Deltamrs4 cells, suggesting that
      Deltamrs3Deltamrs4 cells generate reactive oxygen metabolites. The generation of
      reactive oxygen metabolites in Deltamrs3Deltamrs4 cells was confirmed by use of
      the reporter molecule 2',7'-dichlorodihydrofluorescein diacetate. These results
      suggest that mitochondria-induced oxidant damage is responsible for activating
      Ccc1 and that Fra1 and Tsa1 can reduce oxidant damage.

PMID- 20139088
TI  - Selective translocation of the Bordetella pertussis adenylate cyclase toxin
      across the basolateral membranes of polarized epithelial cells.
AB  - The catalytic domain of Bordetella pertussis adenylate cyclase toxin (ACT)
      translocates directly across the plasma membrane of mammalian cells to induce
      toxicity by the production of cAMP. Here, we use electrophysiology to examine the
      translocation of toxin into polarized epithelial cells that model the mucosal
      surfaces of the host. We find that both polarized T84 cell monolayers and human
      airway epithelial cultures respond to nanomolar concentrations of ACT when
      applied to basolateral membranes, with little or no response to toxin applied
      apically. The induction of toxicity is rapid and fully explained by increases in
      intracellular cAMP, consistent with toxin translocation directly across the
      basolateral membrane. Intoxication of T84 cells occurs in the absence of
      CD11b/CD18 or evidence of another specific membrane receptor, and it is not
      dependent on post-translational acylation of the toxin or on host cell membrane
      potential, both previously reported to be required for toxin action. Thus,
      elements of the basolateral membrane render epithelial cells highly sensitive to
      the entry of ACT in the absence of a specific receptor for toxin binding.

PMID- 20139089
TI  - Molecular interaction and functional regulation of ClC-3 by Ca2+/calmodulin
      dependent protein kinase II (CaMKII) in human malignant glioma.
AB  - Glioblastoma multiforme is the most common and lethal primary brain cancer in
      adults. Tumor cells diffusely infiltrate the brain making focal surgical and
      radiation treatment challenging. The invasion of glioma cells into normal brain
      is facilitated by the activity of ion channels aiding dynamic regulation of cell
      volume. Recent studies have specifically implicated ClC-3, a voltage-gated
      chloride channel, in this process. However, the interaction between ClC-3
      activity and cell movement is poorly understood. Here, we demonstrate that ClC-3
      is highly expressed on the plasma membrane of human glioma cells where its
      activity is regulated through phosphorylation via Ca(2+)/calmodulin-dependent
      protein kinase II (CaMKII). Intracellular infusion of autoactivated CaMKII via
      patch pipette enhanced chloride currents 3-fold, and this regulation was
      inhibited by autocamtide-2 related inhibitory peptide, a CaMKII-specific
      inhibitor. CaMKII modulation of chloride currents was also lost upon stable small
      hairpin RNA knockdown of ClC-3 channels indicating a specific interaction of ClC
      3 and CaMKII. In ClC-3-expressing cells, inhibition of CaMKII reduced glioma
      invasion to the same extent as direct inhibition of ClC-3. The importance of the
      molecular interaction of ClC-3 and CaMKII is further supported by our finding
      that CaMKII co-localizes and co-immunoprecipitates with ClC-3. ClC-3 and CaMKII
      also co-immunoprecipitate in tissue biopsies from patients diagnosed with grade
      IV glioblastoma. These tumor samples show 10-fold higher ClC-3 protein expression
      than nonmalignant brain. These data suggest that CaMKII is a molecular link
      translating intracellular calcium changes, which are intrinsically associated
      with glioma migration, to changes in ClC-3 conductance required for cell
      movement.

PMID- 20139090
TI  - The Rho guanine nucleotide exchange factor AKAP13 (BRX) is essential for cardiac
      development in mice.
AB  - A fundamental biologic principle is that diverse biologic signals are channeled
      through shared signaling cascades to regulate development. Large scaffold
      proteins that bind multiple proteins are capable of coordinating shared signaling
      pathways to provide specificity to activation of key developmental genes.
      Although much is known about transcription factors and target genes that regulate
      cardiomyocyte differentiation, less is known about scaffold proteins that couple
      signals at the cell surface to differentiation factors in developing heart cells.
      Here we show that AKAP13 (also known as Brx-1, AKAP-Lbc, and proto-Lbc), a unique
      protein kinase A-anchoring protein (AKAP) guanine nucleotide exchange region
      belonging to the Dbl family of oncogenes, is essential for cardiac development.
      Cardiomyocytes of Akap13-null mice had deficient sarcomere formation, and
      developing hearts were thin-walled and mice died at embryonic day 10.5-11.0.
      Disruption of Akap13 was accompanied by reduced expression of Mef2C. Consistent
      with a role of AKAP13 upstream of MEF2C, Akap13 siRNA led to a reduction in Mef2C
      mRNA, and overexpression of AKAP13 augmented MEF2C-dependent reporter activity.
      The results suggest that AKAP13 coordinates Galpha(12) and Rho signaling to an
      essential transcription program in developing cardiomyocytes.

PMID- 20139091
TI  - Non-consensus heptamer sequences destabilize the RAG post-cleavage complex,
      making ends available to alternative DNA repair pathways.
AB  - V(D)J recombination entails double-stranded DNA cleavage at the antigen receptor
      loci by the RAG1/2 proteins, which recognize conserved recombination signal
      sequences (RSSs) adjoining variable (V), diversity (D) and joining (J) gene
      segments. After cleavage, RAG1/2 remain associated with the coding and signal
      ends (SE) in a post-cleavage complex (PCC), which is critical for their proper
      joining by classical non-homologous end joining (NHEJ). Certain mutations in
      RAG1/2 destabilize the PCC, allowing DNA ends to access inappropriate repair
      pathways such as alternative NHEJ, an error-prone pathway implicated in
      chromosomal translocations. The PCC is thus thought to discourage aberrant
      rearrangements by controlling repair pathway choice. Since interactions between
      RAG1/2 and the RSS heptamer element are especially important in forming the RAG
      SE complex, we hypothesized that non-consensus heptamer sequences might affect
      PCC stability. We find that certain non-consensus heptamers, including a cryptic
      heptamer implicated in oncogenic chromosomal rearrangements, destabilize the PCC,
      allowing coding and SEs to be repaired by non-standard pathways, including
      alternative NHEJ. These data suggest that some non-consensus RSS, frequently
      present at chromosomal translocations in lymphoid neoplasms, may promote genomic
      instability by a novel mechanism, disabling the PCC's ability to restrict repair
      pathway choice.

PMID- 20139093
TI  - Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of
      IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor
      acute lymphoblastic leukemia.
AB  - Gene expression profiling of 207 uniformly treated children with high-risk B
      progenitor acute lymphoblastic leukemia revealed 29 of 207 cases (14%) with
      markedly elevated expression of CRLF2 (cytokine receptor-like factor 2). Each of
      the 29 cases harbored a genomic rearrangement of CRLF2: 18 of 29 (62%) had a
      translocation of the immunoglobulin heavy chain gene IGH@ on 14q32 to CRLF2 in
      the pseudoautosomal region 1 of Xp22.3/Yp11.3, whereas 10 (34%) cases had a 320
      kb interstitial deletion centromeric of CRLF2, resulting in a P2RY8-CRLF2 fusion.
      One case had both IGH@-CRLF2 and P2RY8-CRLF2, and another had a novel CRLF2
      rearrangement. Only 2 of 29 cases were Down syndrome. CRLF2 rearrangements were
      significantly associated with activating mutations of JAK1 or JAK2, deletion or
      mutation of IKZF1, and Hispanic/Latino ethnicity (Fisher exact test, P < .001 for
      each). Within this cohort, patients with CRLF2 rearrangements had extremely poor
      treatment outcomes compared with those without CRLF2 rearrangements (35.3% vs
      71.3% relapse-free survival at 4 years; P < .001). Together, these observations
      suggest that activation of CRLF2 expression, mutation of JAK kinases, and
      alterations of IKZF1 cooperate to promote B-cell leukemogenesis and identify
      these pathways as important therapeutic targets in this disease.

PMID- 20139094
TI  - Gas6 deficiency in recipient mice of allogeneic transplantation alleviates
      hepatic graft-versus-host disease.
AB  - Growth arrest-specific gene 6 (Gas6) is expressed in antigen-presenting cells and
      endothelial cells (ECs) but not in T cells. When wild-type (WT) or Gas6(-/-) mice
      received allogeneic non-T cell-depleted bone marrow cells, hepatic graft-versus
      host disease (GVHD) was alleviated in Gas6(-/-) recipients regardless of donor
      genotype, but not in WT recipients. T-cell infiltration was more prominent and
      diffuse in WT than in Gas6(-/-) recipients' liver. When mice received 0.5 x 10(6)
      allogeneic T cells with T cell-depleted allogeneic bone marrow, clinical signs
      indicated that GVHD was less severe in Gas6(-/-) than in WT recipients, as shown
      by a significant improvement of the survival and reduced liver GVHD. These data
      demonstrate that donor cells were not involved in the protection mechanism. In
      addition, lack of Gas6 in antigen-presenting cells did not affect WT or Gas6(-/-)
      T-cell proliferation. We therefore assessed the response of WT or Gas6(-/-) ECs
      to tumor necrosis factor-alpha. Lymphocyte transmigration was less extensive
      through Gas6(-/-) than WT ECs and was not accompanied by increases in adhesion
      molecule levels. Thus, the lack of Gas6 in ECs impaired donor T-cell
      transmigration into the liver, providing a rationale for considering Gas6 pathway
      as a potential nonimmunosuppressive target to minimize GVHD in patients receiving
      allogeneic hematopoietic stem cell transplantation.

PMID- 20139095
TI  - Targeted delivery of interferon-alpha via fusion to anti-CD20 results in potent
      antitumor activity against B-cell lymphoma.
AB  - The anti-CD20 antibody rituximab has substantially improved outcomes in patients
      with B-cell non-Hodgkin lymphomas. However, many patients are not cured by
      rituximab-based therapies, and overcoming de novo or acquired rituximab
      resistance remains an important challenge to successful treatment of B-cell
      malignancies. Interferon-alpha (IFNalpha) has potent immunostimulatory properties
      and antiproliferative effects against some B-cell cancers, but its clinical
      utility is limited by systemic toxicity. To improve the efficacy of CD20-targeted
      therapy, we constructed fusion proteins consisting of anti-CD20 and murine or
      human IFNalpha. Fusion proteins had reduced IFNalpha activity in vitro compared
      with native IFNalpha, but CD20 targeting permitted efficient antiproliferative
      and proapoptotic effects against an aggressive rituximab-insensitive human
      CD20(+) murine lymphoma (38C13-huCD20) and a human B-cell lymphoma (Daudi). In
      vivo efficacy was demonstrated against established 38C13-huCD20 grown in
      syngeneic immunocompetent mice and large, established Daudi xenografts grown in
      nude mice. Optimal tumor eradication required CD20 targeting, with 87% of mice
      cured of rituximab-insensitive tumors. Gene knockdown studies revealed that tumor
      eradication required expression of type I IFN receptors on the tumor cell
      surface. Targeting type I IFNs to sites of B-cell lymphoma by fusion to anti-CD20
      antibodies represents a potentially useful strategy for treatment of B-cell
      malignancies.

PMID- 20139096
TI  - Plasmacytoid dendritic cells regulate B-cell growth and differentiation via CD70.
AB  - The ability of plasmacytoid dendritic cells (pDCs) to promote plasma cell
      differentiation and immunoglobulin (Ig) secretion through the production of type
      I interferon and interleukin-6 has been well documented, although the role of
      additional factors, including tumor necrosis factor receptor-ligand interactions,
      has not been addressed. On stimulation with the Toll-like receptor ligand CpG (B
      type, 2006) we found that pDCs exhibit strong and stable expression of CD70, a
      tumor necrosis factor family ligand that binds to its receptor CD27 expressed on
      memory B cells and promotes plasma cell differentiation and Ig secretion. Using a
      pDC/B-cell coculture system, we found that CpG-stimulated pDCs can induce the
      proliferation of CD40L-activated human peripheral B cells and Ig secretion. This
      occurs independently of interferon and residual CpG, and requires physical
      contact between pDCs and B cells. CpG-stimulated pDCs can induce the
      proliferation of both naive and memory B cells, although Ig secretion is
      restricted to the memory subset. Blocking the interaction of CD70 with CD27 using
      an antagonist anti-CD70 antibody reduces the induction of B-cell proliferation
      and IgG secretion by CpG-stimulated pDCs. We have therefore identified CD70 as an
      important factor in the regulation of B-cell growth and differentiation by pDCs.

PMID- 20139097
TI  - Multiple alterations of platelet functions dominated by increased secretion in
      mice lacking Cdc42 in platelets.
AB  - Platelet activation at sites of vascular injury is crucial for hemostasis, but it
      may also cause myocardial infarction or stroke. Cytoskeletal reorganization is
      essential for platelet activation and secretion. The small GTPase Cdc42 has been
      implicated as an important mediator of filopodia formation and exocytosis in
      various cell types, but its exact function in platelets is not established. Here,
      we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild
      thrombocytopenia and a small increase in platelet size in mice. Unexpectedly,
      Cdc42-deficient platelets were able to form normally shaped filopodia and spread
      fully on fibrinogen upon activation, whereas filopodia formation upon selective
      induction of GPIb signaling was reduced compared with wild-type platelets.
      Furthermore, Cdc42-deficient platelets showed enhanced secretion of alpha
      granules, a higher adenosine diphosphate (ADP)/adenosine triphosphate (ATP)
      content, increased aggregation at low agonist concentrations, and enhanced
      aggregate formation on collagen under flow. In vivo, lack of Cdc42 resulted in
      faster occlusion of ferric chloride-injured arterioles. The life span of Cdc42
      deficient platelets was markedly reduced, suggesting increased clearing of the
      cells under physiologic conditions. These data point to novel multiple functions
      of Cdc42 in the regulation of platelet activation, granule organization,
      degranulation, and a specific role in GPIb signaling.

PMID- 20139098
TI  - Latent herpesvirus infection arms NK cells.
AB  - Natural killer (NK) cells were identified by their ability to kill target cells
      without previous sensitization. However, without an antecedent "arming" event, NK
      cells can recognize, but are not equipped to kill, target cells. How NK cells
      become armed in vivo in healthy hosts is unclear. Because latent herpesviruses
      are highly prevalent and alter multiple aspects of host immunity, we hypothesized
      that latent herpesvirus infection would arm NK cells. Here we show that NK cells
      from mice latently infected with Murid herpesvirus 4 (MuHV-4) were armed as
      evidenced by increased granzyme B protein expression, cytotoxicity, and
      interferon-gamma production. NK-cell arming occurred rapidly in the latently
      infected host and did not require acute viral infection. Furthermore, NK cells
      armed by latent infection protected the host against a lethal lymphoma challenge.
      Thus, the immune environment created by latent herpesvirus infection provides a
      mechanism whereby host NK-cell function is enhanced in vivo.

PMID- 20139099
TI  - Nonredundant roles for Runx1 alternative promoters reflect their activity at
      discrete stages of developmental hematopoiesis.
AB  - The transcription factor Runx1 is a pivotal regulator of definitive hematopoiesis
      in mouse ontogeny. Vertebrate Runx1 is transcribed from 2 promoters, the distal
      P1 and proximal P2, which provide a paradigm of the complex transcriptional and
      translational control of Runx1 function. However, very little is known about the
      biologic relevance of alternative Runx1 promoter usage in definitive
      hematopoietic cell emergence. Here we report that both promoters are active at
      the very onset of definitive hematopoiesis, with a skewing toward the P2.
      Moreover, functional and morphologic analysis of a novel P1-null and an
      attenuated P2 mouse model revealed that although both promoters play important
      nonredundant roles in the emergence of definitive hematopoietic cells, the
      proximal P2 was most critically required for this. The nature of the observed
      phenotypes is indicative of a differential contribution of the P1 and P2
      promoters to the control of overall Runx1 levels, where and when this is most
      critically required. In addition, the dynamic expression of P1-Runx1 and P2-Runx1
      points at a requirement for Runx1 early in development, when the P2 is still the
      prevalent promoter in the emerging hemogenic endothelium and/or first committed
      hematopoietic cells.

PMID- 20139100
TI  - Biomarkers in pulmonary embolism.

PMID- 20139101
TI  - The size of the spleen by magnetic resonance imaging in patients with cystic
      fibrosis; with and without diabetes--a novel observational study.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been shown to be a useful tool
      to evaluate the volume of the pancreas. There is currently no information about
      the size of the spleen in cystic fibrosis (CF) patients. PATIENTS AND METHODS: We
      investigated 51 adult volunteers: 28 pancreatic insufficient CF patients [13 with
      CF-related diabetes (CFRD) and 15 non-diabetic] and 23 male non-CF patients [12
      with type 1 diabetes mellitus (T1DM) and 11 healthy control subjects]. Patients
      with known liver cirrhosis or portal hypertension were excluded. The size of the
      spleen was measured in all subjects by an investigator unaware of patients'
      clinical status. For comparison of spleen size in the four study groups only male
      CF patients were included. For CF patients, spleen size was compared with forced
      expiratory volume in 1 s (FEV(1)), body mass index (BMI), total number of days of
      intravenous (IV) antibiotic treatment for pulmonary exacerbations in year
      previous to study, levels of circulating white blood cells, glycosylated
      haemoglobin A1c (HbA1c), and exocrine function of the pancreas, as assessed by
      daily requirement of oral lipase. RESULTS: Amongst the four study groups, spleen
      size was greatest in the male non-diabetic CF patients (P = 0.01). For CF
      patients, spleen size was greater in male compared to female patients (P =
      0.012). For patients with CFRD, there was an inverse correlation between the
      spleen size and HbA1c (r = -0.59, P = 0.04) and the daily intake of supplementary
      lipase (r = -0.63, P = 0.02). The size of the spleen in patients with CFRD, but
      not in CF patients without CFRD, inversely correlated with the days of IV
      antibiotic treatment received in the year previous to the study (r = -0.67, P =
      0.012). There was no correlation between spleen size and BMI, FEV1 and white
      blood cell counts in any group. CONCLUSION: On MRI, the spleen size was greatest
      in male non-diabetic CF patients in comparison with other groups. The size of the
      spleen in CFRD patients was smaller when diabetes was poorly controlled, when
      exocrine pancreatic function was greatly impaired and in those with greater need
      for IV antibiotics in the year prior to the study.

PMID- 20139102
TI  - A national survey of the management of delirium in UK intensive care units.
AB  - BACKGROUND: Delirium is an acute organ dysfunction common amongst patients
      treated in intensive care units. The associated morbidity and mortality are known
      to be substantial. Previous surveys have described which screening tools are used
      to diagnose delirium and which medications are used to treat delirium, but these
      data are not available for the United Kingdom. AIM: This survey aimed to describe
      the UK management of delirium by consultant intensivists. Additionally, knowledge
      and attitudes towards management of delirium were sought. The results will inform
      future research in this area. METHODS: A national postal survey of members of the
      UK Intensive Care Society was performed. A concise two page questionnaire survey
      was sent, with a second round of surveys sent to non-respondents after 6 weeks.
      The questionnaire was in tick-box format. RESULTS: Six hundred and eighty-one
      replies were received from 1308 questionnaires sent, giving a response rate of
      52%. Twenty-five percent of respondents routinely screen for delirium, but of
      these only 55% use a screening tool validated for use in intensive care. The
      majority (80%) of those using a validated instrument used the Confusion
      Assessment Method for the Intensive Care Unit. Hyperactive delirium is treated
      pharmacologically by 95%; hypoactive delirium is treated pharmacologically by
      25%, with haloperidol the most common agent used in both. Over 80% of respondents
      agreed that delirium prolongs mechanical ventilation and hospital stay and
      requires active treatment. CONCLUSION: This UK survey demonstrates screening for
      delirium is sporadic. Pharmacological treatment is usually with haloperidol in
      spite of the limited evidence to support this practice. Hypoactive delirium is
      infrequently treated pharmacologically.

PMID- 20139103
TI  - Hepatitis C and hepatic steatosis.
AB  - Hepatic steatosis is commonly seen in patients with chronic hepatitis C
      infection, and the two together have a greater association than by chance alone.
      Hepatitis C virus is closely associated with lipid metabolism throughout its
      lifecycle. Hepatic steatosis is more common in genotype 3 infection, due to
      direct viral effects including through microsomal triglyceride transfer protein,
      peroxisome proliferator activating receptor, and sterol regulatory element
      binding protein. In non-genotype 3 infection, hepatic steatosis is considered
      largely to be due to alterations in host metabolism, particularly through insulin
      resistance. The clinical relevance of this association has yet to be fully
      explored. Hepatic steatosis is associated with increased hepatic fibrosis and a
      reduced level of sustained virological response to pegylated interferon and
      ribavirin. Small studies trialing adjuvant anti-diabetic therapies or HMG-CoA
      reductase inhibitors with pegylated-interferon and ribavirin have shown an
      improved sustained virological response and reduced viral titer. Furthermore,
      simple lifestyle alterations showed positive effects on parameters of disease
      activity. These insights raise the possibility of novel treatment options.

PMID- 20139105
TI  - Survival of community-associated methicillin-resistant Staphylococcus aureus in 3
      different swimming pool environments (chlorinated, saltwater, and biguanide
      nonchlorinated).
AB  - The aim of this study was to examine the viability of methicillin-resistant
      Staphylococcus aureus (MRSA) in 3 types of swimming pool environments. This study
      demonstrates that after 1 hour, all MRSA inoculants were found to be nonviable in
      chlorinated water, saltwater, and biguanide-treated water. This study indicates
      that swimming pool water that is properly maintained in both public and private
      swim centers is not likely to be a vehicle to spread MRSA from swimmer to
      swimmer.

PMID- 20139106
TI  - The program evaluation of services in a primary care clinic: attaining a medical
      home.
AB  - A program evaluation of a pediatric primary care training clinic was conducted
      using the criteria of a "medical home" set forth by the American Academy of
      Pediatrics (AAP). A total of 107 parents completed questionnaires regarding
      demographics, satisfaction with care, and questions related to the definition of
      medical home. Medical providers completed questionnaires regarding demographics,
      job satisfaction, and community resources. Parents reported acceptable levels of
      satisfaction with the quality of care provided, and the essential parts of the
      medical home definition were met. There were several areas that were designated
      as having room for improvement, including shortening clinic wait times and
      instructing the medical providers to be more sensitive to cultural differences in
      beliefs about health and wellness. The concepts of medical home set forth by the
      AAP are attainable for pediatric primary care clinics, but routine evaluations
      may be needed to ensure that goals continue to be met.

PMID- 20139107
TI  - Facial nerve palsy in the pediatric population.

PMID- 20139108
TI  - Adolescent conversion disorder and the importance of competence discussing sexual
      orientation.

PMID- 20139109
TI  - Inhibition/switching is not necessarily harder than inhibition: an analysis of
      the D-KEFS color-word interference test.
AB  - The Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test
      (CWIT) was designed to improve upon the Stroop task by including an
      inhibition/switching trial, which was designed to be more difficult than the
      inhibition trial in terms of time to completion and number of errors. The D-KEFS
      standardization data support this view. However, in clinical practice, we have
      noticed that many people perform better on the inhibition/switching trial than
      the inhibition trial. We examined the prevalence and correlates of this atypical
      performance pattern on the CWIT. Patients seeking outpatient neuropsychological
      evaluation (n = 119) completed the CWIT as part of a larger test battery. About
      57.1% of patients demonstrated an atypical pattern of performance for either
      completion time or errors. Patients with an atypical pattern for completion time
      were significantly slower at color naming and word reading than patients with a
      typical pattern. Patients with an atypical pattern for errors performed better on
      measures of learning and semantic verbal fluency than patients with a typical
      pattern. A majority of patients in our sample exhibited atypical performance on
      the CWIT, and some preliminary correlates of this pattern might aid clinical
      interpretation.

PMID- 20139110
TI  - Using the Rey-Osterrieth and modified Taylor complex figures with older adults: a
      preliminary examination of accuracy score comparability.
AB  - Although considerable research has now shown that the Rey-Osterrieth Complex
      Figure (ROCF) and its original companion figure, the Taylor Complex Figure (TCF),
      are "not" comparable measures of visuospatial learning and memory, recent studies
      have provided evidence to suggest that the Modified TCF (MTCF) is a comparable
      measure to the ROCF. The primary aim of the present study was to examine the
      comparability of ROCF and MTCF accuracy scores with older adults using the
      traditional incidental learning procedure. A secondary aim was to examine whether
      performance on the two figures showed comparable gender effects and relationships
      with age and education. Comparable recall performance, but not copy performance,
      was found for the two figures in this sample of older adults. No gender
      differences were found on either figure and similar relationships with age and
      education were reported for the two figures. These findings are discussed within
      the context of previous research with consideration given to the clinical
      implications of the findings and future research recommendations.

PMID- 20139111
TI  - Using grip strength force curves to detect simulation: a preliminary
      investigation.
AB  - Analysis of grip strength force curves has successfully detected suboptimal
      effort in industrial rehabilitation research. This study examined force curve
      analysis as an effort measure when grip strength was administered according to
      standardized neuropsychological procedures in a sample without reported
      neurologic and upper extremity injury. Eighty-two undergraduates were randomized
      to control (n = 26), naive simulator (n = 28), and coached simulator (n = 28)
      conditions. Outcome measures included grip strength in kilograms, variables
      calculated from grip strength force curves, and the Word Memory Test (WMT). While
      average force in kilograms was not significantly different between groups,
      significant differences were found on the average to peak force ratio as
      calculated from grip strength force curves. The classification accuracy of
      average to peak force ratio was lower than the WMT, but comparable to other
      effort measures. Force curve analysis may warrant further study in a clinical
      sample.

PMID- 20139112
TI  - Oxidative stress contributes to methamphetamine-induced left ventricular
      dysfunction.
AB  - AIMS: Our aim was to test the hypothesis that the repeated, binge administration
      of methamphetamine would produce oxidative stress in the myocardium leading to
      structural remodeling and impaired left ventricular function. METHODS AND
      RESULTS: Echocardiography and Millar pressure-volume catheters were used to
      monitor left ventricular structure and function in rats subjected to four
      methamphetamine binges (3 mg/kg, iv for 4 days, separated by a 10-day drug-free
      period). Hearts from treated and control rats were used for histological or
      proteomic analysis. When compared with saline treatment, four methamphetamine
      binges produced eccentric left ventricular hypertrophy. The drug also
      significantly impaired systolic function (decreased fractional shortening,
      ejection fraction, and adjusted maximal power) and produced significant diastolic
      dysfunction (increased -dP/dt and tau). Dihydroethedium staining showed that
      methamphetamine significantly increased (285%) the levels of reactive oxygen
      species in the left ventricle. Treatment with methamphetamine also resulted in
      the tyrosine nitration of myofilament (desmin, myosin light chain) and
      mitochondrial (ATP synthase, NADH dehydrogenase, cytochrome c oxidase,
      prohibitin) proteins. Treatment with the superoxide dismutase mimetic, tempol in
      the drinking water prevented methamphetamine-induced left ventricular dilation
      and systolic dysfunction; however, tempol (2.5 mM) did not prevent the diastolic
      dysfunction. Tempol significantly reduced, but did not eliminate dihydroethedium
      staining in the left ventricle, nor did it prevent the tyrosine nitration of
      mitochondrial and contractile proteins. CONCLUSION: This study shows that
      oxidative stress plays a significant role in mediating methamphetamine-induced
      eccentric left ventricular dilation and systolic dysfunction.

PMID- 20139113
TI  - MMP-7 mediates cleavage of N-cadherin and promotes smooth muscle cell apoptosis.
AB  - AIMS: Vascular smooth muscle cell (VSMC) apoptosis can lead to thinning of the
      fibrous cap and plaque instability. We previously showed that cell-cell contacts
      mediated by N-cadherin reduce VSMC apoptosis. This study aimed to determine
      whether matrix-degrading metalloproteinase (MMP)-dependent N-cadherin cleavage
      causes VSMC apoptosis. METHODS AND RESULTS: Induction of human VSMC apoptosis
      using different approaches, including 200 ng/mL Fas ligand (Fas-L) and culture in
      suspension, caused N-cadherin cleavage and resulted in the appearance of a C
      terminal fragment of N-cadherin (approximately 35 kDa). Appearance of this
      fragment during apoptosis was inhibited by 47% with the broad-spectrum MMP
      inhibitor BB-94. We observed retarded cleavage of N-cadherin after treatment with
      Fas-L in aortic mouse VSMCs lacking MMP-7. Furthermore, VSMC apoptosis, measured
      by quantification of cleaved caspase-3, was 43% lower in MMP-7 knockout mouse
      VSMCs compared with wild-type VSMCs following treatment with Fas-L. Addition of
      recombinant active MMP-7 increased the amount of N-cadherin fragment by 82% and
      augmented apoptosis by 53%. The involvement of MMP-7 was corroborated using human
      cells, where a MMP-7 selective inhibitor reduced the amount of fragment formed by
      51%. Importantly, we observed that treatment with Fas-L increased levels of
      active MMP-7 by 80%. Finally, we observed significantly increased cleavage of N
      cadherin, MMP-7 activity, and apoptosis in human atherosclerotic plaques compared
      with control arteries, and a significant reduction in apoptosis in
      atherosclerotic plaques from MMP-7 knockout mice. CONCLUSION: This study
      demonstrates that MMP-7 is involved in the cleavage of N-cadherin and modulates
      VSMC apoptosis, and may therefore contribute to plaque development and rupture.

PMID- 20139114
TI  - Vascular endothelial growth factor is crucial for erythropoietin-induced
      improvement of cardiac function in heart failure.
AB  - AIMS: We intended to delineate the mechanisms of erythropoietin (EPO)-induced
      cardiac vascular endothelial growth factor (VEGF) production and to establish if
      VEGF is crucial for EPO-induced improvement of cardiac performance. METHODS AND
      RESULTS: The effects of EPO on VEGF expression were studied in cultured cardiac
      cells and EPO-treated hearts. The role of VEGF in EPO-induced neovascularization
      was studied with two distinct VEGF-neutralizing antibodies or irrelevant control
      IgG in an aortic sprouting assay and in rats with heart failure (HF) after
      myocardial infarction (MI) treated with EPO. EPO-alfa (10 IU/mL) was used in
      vitro and darbepoetin alfa (40 microg/kg/3 weeks, starting 3 weeks after MI) in
      vivo. EPO stimulated VEGF mRNA expression through the signal transducers and
      activators of transcription-3 (STAT-3) pathway in neonatal rat cardiomyocytes,
      but not in endothelial cells or fibroblasts. Similarly, the direct effects of EPO
      on endothelial sprouting were modest and VEGF independent. In rats with HF, EPO
      increased VEGF protein expression predominantly in cardiomyocytes, associated
      with a 37% increase in capillary density and improved cardiac performance.
      Administration of VEGF-neutralizing antibodies abrogated the salutary effects of
      EPO on cardiac microvascularization and function. VEGF neutralization attenuated
      EPO-induced proliferation of myocardial endothelial cells and reduced myocardial
      incorporation of endothelial progenitor cells (EPCs) in rats with alkaline
      phosphatase-labelled bone marrow cells. CONCLUSION: VEGF is crucial for EPO
      induced improvement of cardiac function in HF. EPO fosters VEGF expression
      predominantly in cardiomyocytes, which in turn stimulates myocardial endothelial
      proliferation and incorporation of EPCs.

PMID- 20139115
TI  - Raised MCP-4 levels in symptomatic carotid atherosclerosis: an inflammatory link
      between platelet and monocyte activation.
AB  - AIMS: Several studies suggest a pro-atherogenic role for the CC chemokine
      receptor 2 (CCR2), thought to reflect interaction with monocyte chemoattractant
      protein (MCP)-1. Based on its ability to attract leucocytes into inflamed tissue,
      we hypothesized a pro-atherogenic role for MCP-4, another CCR2 ligand. METHODS
      AND RESULTS: Our main findings were: (i) patients with symptomatic carotid
      stenosis (n = 29), but not those with asymptomatic plaques (n = 31), had
      significantly raised plasma levels of MCP-4 compared with healthy controls (n =
      20); (ii) in vitro, releasate from activated platelets markedly increased the
      expression of MCP-4 and CCR2 in THP-1 monocytes, and enhanced the MCP-4-mediated
      effect on interleukin-8 secretion in these cells, involving the platelet-derived
      chemokine RANTES; (iii) while MCP-1 had no effect on the release of RANTES and
      interferon-inducible protein of 10 kDa in tumour necrosis factor alpha-pre
      activated THP-1 monocytes, MCP-4 profoundly enhanced the release of these pro
      atherogenic chemokines; and (iv) the data indicate an inflammatory interaction
      between RANTES and MCP-4, involving CCR2, and mRNA levels of these mediators were
      markedly up-regulated within symptomatic atherosclerotic carotid plaque (n = 81).
      CONCLUSION: Our findings suggest that the pro-atherogenic effects of CCR2 may not
      be restricted to interaction with MCP-1, but could also involve activation by MCP
      4, being an inflammatory link between platelet and monocyte activation.

PMID- 20139116
TI  - Neural differences in the processing of semantic relationships across cultures.
AB  - The current study employed functional MRI to investigate the contribution of
      domain-general (e.g. executive functions) and domain-specific (e.g. semantic
      knowledge) processes to differences in semantic judgments across cultures.
      Previous behavioral experiments have identified cross-cultural differences in
      categorization, with East Asians preferring strategies involving thematic or
      functional relationships (e.g. cow-grass) and Americans preferring categorical
      relationships (e.g. cow-chicken). East Asians and American participants underwent
      functional imaging while alternating between categorical or thematic strategies
      to sort triads of words, as well as matching words on control trials. Many
      similarities were observed. However, across both category and relationship trials
      compared to match (control) trials, East Asians activated a frontal-parietal
      network implicated in controlled executive processes, whereas Americans engaged
      regions of the temporal lobes and the cingulate, possibly in response to conflict
      in the semantic content of information. The results suggest that cultures differ
      in the strategies employed to resolve conflict between competing semantic
      judgments.

PMID- 20139117
TI  - Epigenetic regulation of endometrium during the menstrual cycle.
AB  - The endometrium undergoes morphological and functional changes during the
      menstrual cycle which are essential for uterine receptivity. These changes are
      driven by estrogen and progesterone and involve the fine control of many
      different genes-several of which have been identified as being epigenetically
      regulated. Epigenetic modification may therefore influence the functional changes
      in the endometrium required for successful implantation. There is, however, only
      limited information on epigenetic regulation in endometrium. We review the
      potential role of epigenetic regulation of key processes during the menstrual
      cycle and present our own findings following a preliminary study into global
      acetylation levels in the human endometrium. A changing epigenetic state is
      associated with the differentiation of stem cells into different lineages and
      thus may be involved in endometrial regeneration. Histone acetylation is
      implicated in the vascular endothelial growth factor pathway during angiogenesis,
      and studies using histone deacetylase inhibitors suggest an involvement in
      endometrial proliferation and differentiation. The processes of decidualization
      and implantation are also associated with epigenetic change and epigenetic
      modulators show variable expression across the menstrual cycle. Our own studies
      found that endometrial global histone acetylation, as determined by western
      blotting, changed throughout the menstrual cycle and correlated well with
      expected transcription activity during the different phases. This suggests that
      epigenetics may be involved in the regulation of endometrial gene expression
      during the menstrual cycle and that abnormal epigenetic modifications may
      therefore be associated with implantation failure and early pregnancy loss as
      well as with other endometrial pathologies.

PMID- 20139118
TI  - Polymorphisms associated with ventricular tachyarrhythmias: rationale, design,
      and endpoints of the 'diagnostic data influence on disease management and
      relation of genomics to ventricular tachyarrhythmias in implantable
      cardioverter/defibrillator patients (DISCOVERY)' study.
AB  - Implantable cardioverter-defibrillator (ICD) therapy is effective in primary and
      secondary prevention for patients who are at high risk of sudden cardiac death.
      However, the current risk stratification of patients who may benefit from this
      therapy is unsatisfactory. Single nucleotide polymorphisms (SNPs) are DNA
      sequence variations occurring when a single nucleotide in the genome differs
      among members of a species. A novel concept has emerged being that these common
      genetic variations might modify the susceptibility of a certain population to
      specific diseases. Thus, genetic factors may also modulate the risk for
      arrhythmias and sudden cardiac death, and identification of common variants could
      help to better identify patients at risk. The DISCOVERY study is an
      interventional, longitudinal, prospective, multi-centre diagnostic study that
      will enrol 1287 patients in approximately 80 European centres. In the genetic
      part of the DISCOVERY study, candidate gene polymorphisms involved in coding of
      the G-protein subunits will be correlated with the occurrence of ventricular
      arrhythmias in patients receiving an ICD for primary prevention. Furthermore, in
      order to search for additional sequence variants contributing to ventricular
      arrhythmias, a genome-wide association study will be conducted if sufficient a
      priori evidence can be gathered. In the second part of the study, associations of
      SNPs with ventricular arrhythmias will be sought and a search for potential new
      biological arrhythmic pathways will be investigated. As it is a diagnostic study,
      DISCOVERY will also investigate the impact of long-term device diagnostic data on
      the management of patients suffering from chronic cardiac disease as well as
      medical decisions made regarding their treatment.

PMID- 20139119
TI  - Surgical ablation of lone atrial fibrillation on the beating heart: the chaos
      continues.

PMID- 20139120
TI  - Circumferential pulmonary vein ablation of atrial fibrillation via superior vena
      cava approach in a patient with interruption of the inferior vena cava.
AB  - Interruption of the inferior vena cava (IVC) is a very rare congenital
      abnormality. Such patients have many difficulties during ablation procedures. We
      report a case of successful ablation of paroxysmal atrial fibrillation using the
      superior vena cava in a patient with interruption of the IVC.

PMID- 20139121
TI  - Optimal strategy in lead failure.

PMID- 20139122
TI  - SpermCheck Fertility, an immunodiagnostic home test that detects normozoospermia
      and severe oligozoospermia.
AB  - BACKGROUND: A simple and inexpensive home sperm test could be of considerable
      value to couples attempting to conceive and to men curious about their fertility
      potential. A two-strip lateral flow immunochromatographic diagnostic device that
      allows men to evaluate their sperm count at low cost in the privacy of their own
      homes is described. METHODS: The ability of SpermCheck Fertility to predict sperm
      counts obtained using a hemacytometer procedure based on standard World Health
      Organization methodology was assessed. Test results obtained by lay users were
      also compared with those obtained by trained laboratory professionals, and the
      ease of use of the device was evaluated in consumer studies. RESULTS: A total of
      225 semen samples were analyzed in the method comparison, and the performance of
      SpermCheck Fertility was excellent with over 96% of all samples correctly
      classified as normozoospermic (> or =2 x 10(7) sperm/ml), oligozoospermic (5 x
      10(6)-2 x 10(7) sperm/ml) or severely oligozoospermic (<5 x 10(6) sperm/ml).
      Consumer studies with 164 lay users demonstrated that SpermCheck Fertility was
      easy to use. Lay users and laboratory professionals agreed 95% of the time when
      reading the same test independently. Overall, the correct response rate on a 20
      question survey about the test was over 97%. CONCLUSIONS: SpermCheck Fertility is
      a simple and reliable immunodiagnostic test that can quickly inform men as to
      whether their sperm count is normal, low or very low. This home test can assist
      couples in deciding whether to seek comprehensive clinical evaluation of the
      fertility status of the male partner.

PMID- 20139125
TI  - Invited commentary: positivity in practice.
AB  - Positivity, or the experimental treatment assignment assumption, requires that
      there be both exposed and unexposed participants at every combination of the
      values of the observed confounders in the population under study. Positivity is
      essential for inference but is often overlooked in practice by epidemiologists.
      This issue of the Journal includes 2 articles featuring discussions related to
      positivity. Here the authors define positivity, distinguish between deterministic
      and random positivity, and discuss the 2 relevant papers in this issue. In
      addition, the commentators illustrate positivity in simple 2 x 2 tables, as well
      as detail some ways in which epidemiologists may examine their data for
      nonpositivity and deal with violations of positivity in practice.

PMID- 20139124
TI  - Time scale and adjusted survival curves for marginal structural cox models.
AB  - Typical applications of marginal structural time-to-event (e.g., Cox) models have
      used time on study as the time scale. Here, the authors illustrate use of time on
      treatment as an alternative time scale. In addition, a method is provided for
      estimating Kaplan-Meier-type survival curves for marginal structural models. For
      illustration, the authors estimate the total effect of highly active
      antiretroviral therapy on time to acquired immunodeficiency syndrome (AIDS) or
      death in 1,498 US men and women infected with human immunodeficiency virus and
      followed for 6,556 person-years between 1995 and 2002; 323 incident cases of
      clinical AIDS and 59 deaths occurred. Of the remaining 1,116 participants, 77%
      were still under observation at the end of follow-up. By using time on study, the
      hazard ratio for AIDS or death comparing always with never using highly active
      antiretroviral therapy from the marginal structural model was 0.52 (95%
      confidence interval: 0.35, 0.76). By using time on treatment, the analogous
      hazard ratio was 0.44 (95% confidence interval: 0.32, 0.60). In time-to-event
      analyses, the choice of time scale may have a meaningful impact on estimates of
      association and precision. In the present example, use of time on treatment
      yielded a hazard ratio further from the null and more precise than use of time on
      study as the time scale.

PMID- 20139126
TI  - Pooling dietary data using questionnaires with open-ended and predefined
      responses: implications for comparing mean intake or estimating odds ratios.
AB  - In the current era of diet-gene analyses, large sample sizes are required to
      uncover the etiology of complex diseases. As such, consortia form and often
      combine available data. Food frequency questionnaires, which commonly use 2
      different types of responses about the frequency of intake (predefined responses
      and open-ended responses), may be pooled to achieve the desired sample size. The
      common practice is to categorize open-ended responses into the predefined
      response categories. A problem arises when the predefined categories are
      noncontiguous: possible open-ended responses may fall in gaps between the
      predefined categories. Using simulated data modeled from frequency of intake
      among 1,664 controls in a lung cancer case-control study at The University of
      Texas M. D. Anderson Cancer Center (Houston, Texas, 2000-2005), the authors
      describe the effect of different categories of open-ended responses that fall in
      between noncontiguous, predefined response sets on estimates of the mean
      difference in intake and the odds ratios. A significant inflation of false
      positives appears when comparing mean differences of intake, while the bias in
      estimating odds ratios may be acceptably small. Therefore, if pooling data cannot
      be restricted to the same type of response, inferences should focus on odds ratio
      estimation to minimize bias.

PMID- 20139128
TI  - The association between persistent fetal occiput posterior position and perinatal
      outcomes: an example of propensity score and covariate distance matching.
AB  - In a retrospective cohort study of 18,880 full-term, cephalic singletons born in
      San Francisco, California, during 1976-2001, the authors used multivariable
      logistic regression (MVLR) and propensity score analysis (PSA) to examine the
      association between persistent fetal occiput posterior (OP) position and
      perinatal outcomes. The principles and applications of these techniques are
      compared and discussed. Pregnancies with OP positions at delivery were compared
      with those with occiput anterior positions. Perinatal outcomes were examined as
      adjusted odds ratios determined by MVLR and PSA and as risk differences
      determined by propensity score matched bootstrapping based on covariate distance.
      Persistent OP position was associated with operative delivery and maternal
      morbidity. The odds ratio estimates based on PSA were somewhat larger than those
      obtained with standard MVLR, and the confidence intervals were narrower. When
      statistical inference was evaluated with the permutation test, the results were
      more consistent with the PSA. These analyses demonstrate that PSA is likely to
      provide more precise estimates of exposure associations and more reliable
      statistical inferences than MVLR. The authors show that PSA can be extended with
      Mahalanobis distance matching to obtain estimates of risk difference between
      exposed and unexposed subjects that avoid violations of the experimental
      treatment assignment (positivity) assumption that is required for valid causal
      inference.

PMID- 20139129
TI  - Effects of socioeconomic and racial residential segregation on preterm birth: a
      cautionary tale of structural confounding.
AB  - Confounding associated with social stratification or other selection processes
      has been called structural confounding. In the presence of structural
      confounding, certain covariate strata will contain only subjects who could never
      be exposed, a violation of the positivity or experimental treatment effect
      assumption. Thus, structural confounding can prohibit the exchangeability
      necessary for meaningful causal contrasts across levels of exposure. The authors
      explored the presence and magnitude of structural confounding by estimating the
      independent effects of neighborhood deprivation and neighborhood racial
      composition (segregation) on rates of preterm birth in Wake and Durham counties,
      North Carolina (1999-2001). Tabular analyses and random-intercept fixed-slope
      multilevel logistic models portrayed different structural realities in these
      counties. The multilevel modeling results suggested some nonsignificant effect of
      residence in tracts with high levels of socioeconomic deprivation or racial
      residential segregation on adjusted odds of preterm birth for white and black
      women living in these counties, and the confidence limit ratios indicated fairly
      consistent levels of precision around the estimates. The results of the tabular
      analysis, however, suggested that many of these regression modeling findings were
      off-support and based on no actual data. The implications for statistical and
      public health inference, in the presence of no data, are considered.

PMID- 20139130
TI  - An integrative genomic approach in oesophageal cells identifies TRB3 as a bile
      acid responsive gene, downregulated in Barrett's oesophagus, which regulates NF
      kappaB activation and cytokine levels.
AB  - Reflux of gastroduodenal contents and consequent inflammatory responses are
      associated with the development of Barrett's oesophagus (BO) and the promotion of
      oesophageal adenocarcinoma (OAC). Deregulation of inflammatory processes is a
      hallmark of oesophageal cancer. In this study, we aimed to investigate (i) the
      transcriptional responses to deoxycholic acid (DCA) in cell lines representative
      of either end of the oesophageal cancer sequence, (ii) the expression of DCA
      regulated genes in data charting oesophageal carcinogenesis and (iii) the impact
      of these genes on oesophageal inflammatory signalling. Gene expression
      microarrays were utilized to demonstrate differential transcriptional responses
      between squamous (HET-1A) and adenomatous (SKGT4) cell lines exposed to DCA.
      Differential basal and DCA-inducible expression of cytokines such as interleukin
      (IL) 8 was observed between both cell types. A cohort of DCA-regulated genes
      specific to each cell type was identified in microarray experimentation and
      subsequently validated. Cell type-specific genes included TRB3, CXCL14, GDF15 and
      LIF in HET-1A cells, with COX2-, ESM1-, URHF1- and IL1alpha-and IL1beta-specific
      expression in SKGT4 cells. Over 30% of the genes altered in BO and OAC were shown
      to be regulated by DCA utilizing an integrative genomic approach. One such gene,
      tribbles-homology-3 (TRB3) was induced specifically in HET-1A cells, absent in
      SKGT4 cells and decreased in BO samples in silico and in vivo. Inhibition and re
      introduction of TRB3 in HET-1A and SKGT4 cells, respectively, demonstrated the
      ability of TRB3 to regulate inflammatory signalling through nuclear factor
      kappaB. This study identifies mechanisms through which bile acids such as DCA, in
      conjunction with the loss of key signalling molecules, could regulate oesophageal
      metaplasticity.

PMID- 20139131
TI  - Reduction of biofilm on orthodontic brackets with the use of a
      polytetrafluoroethylene coating.
AB  - SUMMARY: Treatment with fixed orthodontic appliances can cause enamel
      demineralization by increased biofilm adhesion. The purpose of the present study
      was to investigate whether a polytetrafluoroethylene (PTFE) coating reduces
      biofilm formation on orthodontic brackets. One PTFE-coated bracket and one
      uncoated stainless steel bracket were bonded symmetrically on the first or second
      (four maxillary and nine mandibular) primary molars in 13 adolescent patients
      (five females and eight males, aged 11.2 +/- 2.8 years; four dropouts) for 8
      weeks. Quantitative biofilm formation on brackets was analysed with the
      Rutherford backscattering detection (RBSD) method, a scanning electron microscopy
      technique. A total of five RBSD micrographs were obtained per bracket with views
      from the buccal, mesial, distal, cervical, and occlusal aspects. A two-sided
      paired t-test was used to compare data. A P-value less than 0.05 was considered
      significant. Total biofilm formation was 4.0 +/- 3.6 per cent of the surface on
      the PTFE-coated brackets and 22.2 +/- 5.4 per cent on uncoated brackets.
      Differences between the two groups were statistically significant (P < 0.05).
      Pairwise comparison of biofilm formation with respect to location (buccal,
      mesial, distal, cervical, and occlusal) revealed a significantly lower biofilm
      accumulation on PTFE-coated brackets on all surfaces. The results indicate that
      PTFE coating of brackets reduces biofilm adhesion to a minimum and might have the
      potential to reduce iatrogenic side effects, e.g. decalcification during
      orthodontic treatment with fixed appliances.

PMID- 20139132
TI  - Variations in surface characteristics and corrosion behaviour of metal brackets
      and wires in different electrolyte solutions.
AB  - The aim of this study was to assess the surface characteristics and to compare
      the corrosion potential of metal brackets and wires in environments containing
      different media. Four brands of metal brackets and two types of orthodontic wires
      [stainless steel and nickel-titanium (NiTi)] were investigated. An
      electrochemical assay was used to compare the corrosion potential (V) of the
      brackets and wires in different electrolyte media at 37 degrees C. The test media
      were acidulated sodium fluoride (NaF) and pH 4 and pH 6 artificial saliva
      solutions. The data were analysed using analysis of variance with a predetermined
      significance level of alpha = 0.05. Scanning electron microscopy (SEM) was used
      to observe surface defects and corrosion. The results of the potentiodynamic
      curve showed that most brands of metal brackets were easily corroded in the NaF
      and pH 4 environments, while the NiTi and stainless steel wires were easily
      corroded in the pH 4 artificial saliva. SEM observations showed that defects or
      pitting corrosion occurred on the surfaces of the brackets and wires in all
      tested media.

PMID- 20139133
TI  - A high level of physical fitness is associated with more efficient response
      preparation in older adults.
AB  - This study assessed the relationship between cardiovascular fitness and temporal
      preparation in elderly persons. 110 older adults (aged 60-69 or 70-79 years) were
      sorted into low- and high-fit groups based on aerobic fitness level estimated
      with a walking test. Response preparation processes were assessed with reaction
      time tasks in which short (1, 3, 5 s) and long (5, 7, 9 s) preparatory intervals
      varied randomly. The results suggest a better ability in high-fit individuals to
      maintain preparation over time (up to 9 s). Results of the present study suggest
      that in older adults, a high level of aerobic fitness is associated with more
      efficient response preparation processes.

PMID- 20139134
TI  - "Going with the flow"--a comparison of interstate elderly migration during 1970
      2000 using the (I)PUMS versus full census data.
AB  - OBJECTIVES: We investigate how much state-to-state elderly migration patterns
      have changed during 1970-2000 and compare the findings from 2 commonly used
      sources of data, the census flow tabulations and the integrated public use
      microdata series (IPUMS). METHODS: We calculate descriptive statistics such as
      migration rates, the distribution of top destination and origin states, and a new
      migration Herfindahl-Hirschman Index that measures geographic concentration.
      Comparisons over time and between data sources are formalized using correlations
      and regression analyses that permit persistent flow patterns. RESULTS: After an
      increase between 1970 and 1980, elderly migration rates have been stable, with a
      slight decline. Elderly migration has become less geographically concentrated;
      the decline of California and Florida and ascension of Nevada and the Carolinas
      as top destinations are evident. Correlation and regression analyses reveal that
      migration patterns are overall very persistent over time, especially using census
      tabulations based on a larger sample. DISCUSSION: Elderly migration patterns have
      been quite stable since 1970. Using the IPUMS, as most migration studies do,
      exaggerates the changes in elderly migration over time in both descriptive and
      statistical analyses, a result that is likely due to its smaller sample size and
      the relative rarity of an interstate move.

PMID- 20139135
TI  - Recent developments in survival analysis.

PMID- 20139136
TI  - A pilot trial of telemedicine-assisted, integrated care for patients with
      advanced amyotrophic lateral sclerosis and their caregivers.
AB  - Patients with amyotrophic lateral sclerosis (ALS) need a care programme as the
      disease progresses. We used telemedicine-assisted integrated care (TAIC) in 40
      patients with ALS, for a mean duration of 8.6 months (range 1-12). A nurse-tutor
      played the key role, supported by respiratory physicians, neurologists and
      psychologists. Each patient used a portable pulse oximeter during the daily
      telephone contacts to assess clinical/oxygen variations. Patients also completed
      a satisfaction questionnaire. During the study period, each patient used TAIC at
      least five times per month. There were 1907 scheduled telephone calls (86% of the
      total) and 317 unscheduled calls. Of the unscheduled calls, 84% were managed by
      the nurse-tutor and only 16% of them required specialist intervention. The most
      common item was the ALS clinical interview (58%), followed by the description of
      acute symptoms, cough ability and oxygenation. TAIC staff recommended 4 out of 12
      emergency hospital admissions (33%) and 77% of the other hospitalizations.
      Patients and caregivers were extremely satisfied (79%) with the nurse assistance
      provided and the patients' confidence in handling their disease improved in 71%
      of the cases. TAIC provides a nurse-centred, home-monitoring programme that can
      be a useful way of following up ALS patients.

PMID- 20139138
TI  - Pharmaceutical review using telemedicine--a before and after feasibility study.
AB  - Only 42 of the 116 public hospitals in Queensland employ qualified pharmacists to
      staff their pharmacies. We undertook a feasibility study to determine if
      pharmaceutical reviews, undertaken face-to-face by a visiting pharmacist, could
      be replicated using telemedicine. The study was conducted in two phases, with the
      same pharmacist coordinating the project from the main hospital to two rural
      hospitals, which relied on supply nurses for all their pharmaceutical services.
      All inpatients admitted between October 2006 and May 2007 were included in the
      study. In Phase I the pharmacist made weekly visits to both facilities, to
      perform face-to-face pharmaceutical reviews of the current inpatients. In Phase
      2, all pharmaceutical reviews were performed remotely by the pharmacist by
      telephone or videoconference. In Phase 1, 186 pharmaceutical activities were
      performed (mean 3.9 per patient). Of these, 78 pharmacist-initiated changes were
      recommended and 47 (60%) were implemented. In Phase 2, a total of 296 activities
      were performed (mean 3.1 per patient) and of the 140 recommendations made by the
      remote pharmacist, 74 (53%) were accepted. Of the accepted recommendations, there
      were 11 major interventions (those with a potential to prevent harm to the
      patient) in Phase 1 and 32 in Phase 2. There were no significant differences in
      the pharmaceutical activity rates in the two phases. Telepharmacy therefore may
      be an effective method of providing pharmaceutical reviews for patients in rural
      inpatient facilities, without an on-site pharmacist.

PMID- 20139139
TI  - Expert visual guidance of ultrasound for telemedicine.
AB  - Expert visual guidance (EVG) is computer assistance that displays to the examiner
      how the image plane moves towards (or away from) a desired anatomical location as
      the ultrasound probe is manipulated over the patient's body. We tested whether
      EVG by a remote expert could assist inexperienced examiners in acquiring
      abdominal ultrasound images. The inexperienced examiners were 20 medical
      students, who were randomly assigned to verbal instruction alone (Group 1) or to
      EVG (Group 2). The examiners were tested on their ability to visualize the
      abdominal aorta and the right kidney. Group 2 was more successful in identifying
      specified anatomy in longitudinal and cross-sectional views of the aorta (95 vs.
      75%, P = 0.032) and kidney (98 vs. 88%, P = 0.09). The groups succeeded equally
      well in obtaining a true cross-sectional view of the aorta. Kidney length was
      also similar when measured by the two groups. The results demonstrate that an
      inexperienced ultrasonographer can be significantly assisted by EVG compared to
      verbal instruction alone. This could be useful for tele-mentoring in rural
      hospitals as well as for teaching, both in person and at a remote site.

PMID- 20139140
TI  - Costs and benefits of tele-endoscopy clinics in a remote location.
AB  - We assessed the cost and benefits of tele-endoscopy clinics in a remote location
      in Scotland. Before the introduction of a tele-endoscopy service, patients whose
      symptoms suggested possible cancer of the airways had to travel to the mainland
      (to Aberdeen) to receive an endoscopy. The costs of staff, capital, disposables
      and travel were estimated for the tele-endoscopy clinic and for the conventional,
      mainland clinic. The benefits of the two types of clinic were estimated from a
      sample of the general public using a survey method called the discrete choice
      experiment. The average cost per patient was lower for the tele-endoscopy clinic
      (pounds sterling 353) than for the mainland clinic (pounds sterling 381). This
      was true if more than 27 patients were seen per year. Assuming equal waiting
      times, individuals preferred the tele-endoscopy clinic to the mainland clinic.
      The net benefits were larger for tele-endoscopy clinics as long as the additional
      waiting time was not longer than four weeks. Tele-endoscopy clinics in Shetland
      are an efficient alternative to conventional practice. The results are sensitive
      to both economies of scale and scope. The model can readily be applied to
      mainland communities outside the main population centres in Scotland.

PMID- 20139141
TI  - Detection of GES-5-producing Klebsiella pneumoniae in Brazil.

PMID- 20139142
TI  - Activity of telavancin against heterogeneous vancomycin-intermediate
      Staphylococcus aureus (hVISA) in vitro and in an in vivo mouse model of
      bacteraemia.
AB  - OBJECTIVES: Infections caused by heterogeneous vancomycin-intermediate
      Staphylococcus aureus (hVISA) are associated with high rates of vancomycin
      treatment failure. Telavancin is a bactericidal lipoglycopeptide active in vitro
      against Gram-positive pathogens including hVISA and vancomycin-intermediate S.
      aureus (VISA). This study characterizes the microbiological activity of
      telavancin against vancomycin-susceptible S. aureus (VSSA), hVISA and VISA
      strains. METHODS: Reference strains of VSSA, hVISA and VISA were assessed for
      potential telavancin heteroresistance by population analysis. In addition, the
      efficacies of telavancin (40 mg/kg subcutaneously every 12 h for 4 days) and
      vancomycin (110 mg/kg subcutaneously every 12 h for 8 days) were compared in a
      neutropenic murine model (immunocompromised female non-Swiss albino mice) of
      bacteraemia caused by hVISA strain Mu3. Blood and spleen bacterial titres were
      quantified from cohorts of mice euthanized pre-treatment and at 24 h intervals
      post-treatment for 8 days. RESULTS: Telavancin was active against all strains of
      S. aureus tested, with MIC values < or =0.5 mg/L. Population analyses revealed no
      evidence of subpopulations with reduced susceptibility to telavancin. In the
      murine bacteraemia model of hVISA infection, all animals were bacteraemic pre
      treatment and mortality was 100% within 16-24 h post-infection in untreated
      animals. Treatment with telavancin was associated with lower spleen bacterial
      titres, lower rates of bacteraemia and lower overall mortality than treatment
      with vancomycin. CONCLUSIONS: These in vitro and pre-clinical in vivo studies
      demonstrate that telavancin has the potential to be efficacious in infections
      caused by hVISA.

PMID- 20139143
TI  - Reassessment of intravenous antibiotic therapy using a reminder or direct
      counselling.
AB  - OBJECTIVES: Encouraging reassessment of intravenous antibiotic therapy at days 3
      4 is an important step in the management of patients and may be done by
      delivering a questionnaire or through systematic infectious disease physician
      (IDP) advice to prescribers. PATIENTS AND METHODS: In this before-and-after
      study, prescriptions of 13 selected intravenous antibiotics from surgical or
      medical wards were screened from a computer-generated listing and prospectively
      included. Three strategies were compared over three consecutive 8 week periods:
      conventional management by the attending physician (control group); distribution
      of a questionnaire to the physician (questionnaire group); or distribution of the
      questionnaire followed by IDP advice (Q-IDP group). The primary outcome was the
      percentage of modifications of antibiotic therapy at day 4, including withdrawal
      of therapy, de-escalation, oral switch or reducing the planned duration of
      therapy. RESULTS: Overall, 402 prescriptions were included. At day 4, 48.9% and
      54.5% of prescriptions were modified in the control and questionnaire groups,
      respectively (P = 0.35). In contrast, more prescriptions (66.2%) were modified in
      the Q-IDP group as compared with the control group (P = 0.004). Stopping therapy
      in the absence of apparent bacterial infection occurred significantly more often
      in the Q-IDP group than in the control (P < 0.0001) or questionnaire groups (P =
      0.002). CONCLUSIONS: This study shows a modest impact of only distributing a
      questionnaire aimed at reminding physicians to reassess therapy, whereas
      systematic IDP intervention improves the modification rate.

PMID- 20139144
TI  - Use of a prolactin-Cre/ROSA-YFP transgenic mouse provides no evidence for
      lactotroph transdifferentiation after weaning, or increase in
      lactotroph/somatotroph proportion in lactation.
AB  - In rats, a shift from somatotroph dominance to lactotroph dominance during
      pregnancy and lactation is well reported. Somatotroph to lactotroph
      transdifferentiation and increased lactotroph mitotic activity are believed to
      account for this and associated pituitary hypertrophy. A combination of cell
      death and transdifferentiation away from the lactotroph phenotype has been
      reported to restore non-pregnant pituitary proportions after weaning. To attempt
      to confirm that a similar process occurs in mice, we generated and used a
      transgenic reporter mouse model (prolactin (PRL)-Cre/ROSA26-expression of yellow
      fluorescent protein (EYFP)) in which PRL promoter activity at any time resulted
      in permanent, stable, and highly specific EYFP. Triple immunochemistry for GH,
      PRL, and EYFP was used to quantify EYFP+ve, PRL-ve, and GH+ve cell populations
      during pregnancy and lactation, and for up to 3 weeks after weaning, and
      concurrent changes in cell size were estimated. At all stages, the EYFP reporter
      was expressed in 80% of the lactotrophs, but in fewer than 1% of other pituitary
      cell types, indicating that transdifferentiation from those lactotrophs where
      reporter expression was activated is extremely rare. Contrary to expectations, no
      increase in the lactotroph/somatotroph ratio was seen during pregnancy and
      lactation, whether assessed by immunochemistry for the reporter or PRL: findings
      confirmed by PRL immunochemistry in non-transgenic mice. Mammosomatotrophs were
      rarely encountered at the age group studied. Individual EYFP+ve cell volumes
      increased significantly by mid-lactation compared with virgin animals. This, in
      combination with a modest and non-cell type-specific estrogen-induced increase in
      mitotic activity, could account for pregnancy-induced changes in overall
      pituitary size.

PMID- 20139145
TI  - Resistance exercise, skeletal muscle FOXO3A, and 85-year-old women.
AB  - This investigation examined Akt-FOXO3A signaling in young women (YW) and old
      women (OW) before and after 12 weeks of high-intensity resistance training.
      Muscle biopsies were taken from the vastus lateralis before and immediately after
      resistance exercise (RE) in the untrained and trained states. In response to RE
      in YW and OW, phospho Akt Thr308 increased in untrained and trained states, with
      no change on Ser473 site. FOXO3A-Ser253 site was dephosphorylated in untrained
      state among YW and OW, and nuclear phospho-FOXO3A increased mainly in YW in
      trained state. In the basal state, OW displayed lower cytosolic phospho-FOXO3A
      before training, higher total nuclear FOXO3A, and a trend for higher nuclear-to
      cytosolic FOXO3A ratio versus YW after 12 weeks. Basal level MuRF-1 and myostatin
      mRNA decreased in YW, while OW increased myostatin mRNA after 12-weeks. These
      data suggest that FOXO3A signaling and FOXO3A-related target gene expression are
      altered in OW and may partially explain the attenuated training adaptations
      previously reported in these octogenarian women.

PMID- 20139146
TI  - Revisiting the contribution of cis-elements to expression divergence between
      duplicated genes: the role of chromatin structure.
AB  - Although divergence in expression is thought to be a hallmark of functional
      dispersal between paralogs postduplication, there is currently a limited
      understanding of the mechanisms underlying the necessary transcriptional
      alterations as recent studies have suggested that only a very small proportion of
      expression variation could be explained by transcriptional variation between
      paralogs. To further this understanding, we examined comprehensively curated
      regulatory interactions and genomewide nucleosome occupancy in budding yeast to
      specifically determine the contribution of cis-elements to expression divergence
      between extant duplicates. We found that divergence in activation by
      transcription factors plays a more important role in expression divergence of
      paralogs than previously appreciated; further, analysis of promoter chromatin
      structure demonstrated that differential nucleosome organization is coupled with
      divergent expression of paralogs. By incorporating information of cis-elements
      encoding transcriptional regulation and chromatin structure, we improved the
      fraction of expression variation that was previously shown to be explained based
      on known cis-transcriptional effects by approximately 3-fold. Taken together, our
      analysis highlights the importance of chromatin divergence involved in expression
      evolution between paralogs.

PMID- 20139147
TI  - Molecular basis of the waxy endosperm starch phenotype in broomcorn millet
      (Panicum miliaceum L.).
AB  - Waxy varieties of the tetraploid cereal broomcorn millet (Panicum miliaceum L.)
      have endosperm starch granules lacking detectable amylose. This study
      investigated the basis of this phenotype using molecular and biochemical methods.
      Iodine staining of starch granules in 72 plants from 38 landrace accessions found
      58 nonwaxy and 14 waxy phenotype plants. All waxy types were in plants from
      Chinese and Korean accessions, a distribution similar to that of the waxy
      phenotype in other cereals. Granule-bound starch synthase I (GBSSI) protein was
      present in the endosperm of both nonwaxy and waxy individuals, but waxy types had
      little or no granule-bound starch synthase activity compared with the wild types.
      Sequencing of the GBSSI (Waxy) gene showed that this gene is present in two
      different forms (L and S) in P. miliaceum, which probably represent homeologues
      derived from two distinct diploid ancestors. Protein products of both these forms
      are present in starch granules. We identified three polymorphisms in the exon
      sequence coding for mature GBSSI peptides. A 15-bp deletion has occurred in the S
      type GBSSI, resulting in the loss of five amino acids from glucosyl transferase
      domain 1 (GTD1). The second GBSSI type (L) shows two sequence polymorphisms. One
      is the insertion of an adenine residue that causes a reading frameshift, and the
      second causes a cysteine-tyrosine amino acid polymorphism. These mutations appear
      to have occurred in parallel from the ancestral allele, resulting in three GBSSI
      L alleles in total. Five of the six possible genotype combinations of the S and L
      alleles were observed. The deletion in the GBSSI-S gene causes loss of protein
      activity, and there was 100% correspondence between this deletion and the waxy
      phenotype. The frameshift mutation in the L gene results in the loss of L-type
      protein from starch granules. The L isoform with the tyrosine residue is present
      in starch granules but is nonfunctional. This loss of function may result from
      the substitution of tyrosine for cysteine, although it could not be determined
      whether the cysteine isoform of L represents the functional type. This is the
      first characterization of mutations that occur in combination in a functionally
      polyploid species to give a fully waxy phenotype.

PMID- 20139148
TI  - The health implications of apologizing after an adverse event.
AB  - Australia is working towards a National Open Disclosure Standard in which all
      adverse incidents are disclosed to patients in all health-care facilities in the
      country. Among the many good reasons for this approach, one that has not
      attracted attention is the possibility that disclosure of an adverse incident may
      moderate its impact on the recovery and general health of patients. In this
      article, we discuss this perspective with reference to relevant psychological and
      physiological literature. In the absence of existing research that pursues this
      specific hypothesis on disclosure and health effects, we called on the extensive
      evidence that analogous traumatic events can lead to a prolonged state of
      negative affect and hyperarousal that are deleterious to recovery and health.
      This state is called 'unforgiveness' by some psychologists. Research suggests
      that unforgiveness can be alleviated if people who feel aggrieved forgive those
      they blame for the harm. Forgiving is a complex process, but there is evidence
      that it is promoted by an apologetic response that incorporates expressions of
      responsibility, regret and intended action. With the exception of responsibility,
      these components are part of open disclosure as envisaged in the Standard. We
      conclude that there is preliminary support from the psychological and
      physiological literature for further investigation of the hypothesis that
      disclosure can moderate the recovery and health of patients after an adverse
      incident, provided that the disclosure incorporates an admission of
      responsibility.

PMID- 20139149
TI  - Estrogen promotes stress sensitivity in a prefrontal cortex-amygdala pathway.
AB  - We have recently reported in male rats that medial prefrontal cortex (mPFC)
      neurons that project to the basolateral nucleus of the amygdala (BLA) are
      resilient to stress-induced dendritic remodeling. The present study investigated
      whether this also occurs in female rats. This pathway was identified using the
      retrograde tracer Fast Blue injected into the BLA of ovariectomized female rats
      with estrogen replacement (OVX + E) and without (OVX + veh). Animals were exposed
      for 10 days either to 2-h immobilization stress or to home cage rest, after which
      layer III mPFC neurons that were either retrogradely labeled by Fast Blue or
      unlabeled were filled with Lucifer Yellow and analyzed for apical dendritic
      length and spine density. No dendritic remodeling occurred in unlabeled neurons
      from OVX + veh or OVX + E animals. In BLA-projecting neurons, however, stress had
      no effect on length in OVX + veh animals, but stressed OVX + E females showed
      greater dendritic length than controls at intermediate branches. Stress also
      caused an increase in spine density in all neurons in OVX + veh animals and a
      spine density increase in BLA-projecting neurons in OVX + E females. Estrogen
      also increased spine density on BLA-projecting neurons in unstressed animals.
      These data demonstrate both independent effects of estrogen on pyramidal cell
      morphology and effects that are interactive with stress, with the BLA-projecting
      neurons being sensitive to both kinds of effects.

PMID- 20139151
TI  - Risk-adapted FDG-PET/CT-based follow-up in patients with diffuse large B-cell
      lymphoma after first-line therapy.
AB  - BACKGROUND: The purpose of this study was to evaluate the impact of 2-[fluorine
      18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG
      PET/CT) during follow-up of patients with diffuse large B-cell lymphoma (DLBCL)
      being in complete remission or unconfirmed complete remission after first-line
      therapy. PATIENTS AND METHODS: DLBCL patients receiving FDG-PET/CT during follow
      up were analyzed retrospectively. Confirmatory biopsy was mandatory in cases of
      suspected disease recurrence. RESULTS: Seventy-five patients were analyzed and 23
      (30%) had disease recurrence. The positive predictive value (PPV) of FDG-PET/CT
      was 0.85. Patients >60 years [P = 0.036, hazard ratio (HR) = 3.82, 95% confidence
      interval (CI) 1.02-7.77] and patients with symptoms indicative of a relapse (P =
      0.015; HR = 4.1; 95% CI 1.20-14.03) had a significantly higher risk for relapse.
      A risk score on the basis of signs of relapse, age >60 years, or a combination of
      these factors identified patients at high risk for recurrence (P = 0.041).
      CONCLUSIONS: FDG-PET/CT detects recurrent DLBCL after first-line therapy with
      high PPV. However, it should not be used routinely and if only in selected high
      risk patients to reduce radiation burden and costs. On the basis of our
      retrospective data, FDG-PET/CT during follow-up is indicated for patients <60
      years with clinical signs of relapse and in patients >60 years with and without
      clinical signs of relapse.

PMID- 20139150
TI  - Reading networks at rest.
AB  - Resting-state functional connectivity (RSFC) approaches offer a novel tool to
      delineate distinct functional networks in the brain. In the present functional
      magnetic resonance imaging (fMRI) study, we elucidated patterns of RSFC
      associated with 6 regions of interest selected primarily from a meta-analysis on
      word reading (Bolger DJ, Perfetti CA, Schneider W. 2005. Cross-cultural effect on
      the brain revisited: universal structures plus writing system variation. Hum
      Brain Mapp. 25: 92-104). In 25 native adult readers of English, patterns of
      positive RSFC were consistent with patterns of task-based activity and functional
      connectivity associated with word reading. Moreover, conjunction analyses
      highlighted the posterior left inferior frontal gyrus and the posterior left
      middle temporal gyrus (post-LMTG) as potentially important loci of functional
      interaction among 5 of the 6 reading networks. The significance of the post-LMTG
      has typically been unappreciated in task-based studies on unimpaired readers but
      is frequently reported to be a locus of hypoactivity in dyslexic readers and
      exhibits intervention-induced changes of activity in dyslexic children. Finally,
      patterns of negative RSFC included not only regions of the so-called default mode
      network but also regions involved in effortful controlled processes, which may
      not be required once reading becomes automatized. In conclusion, the current
      study supports the utility of resting-state fMRI for investigating reading
      networks and has direct relevance for the understanding of reading disorders such
      as dyslexia.

PMID- 20139152
TI  - Need for a new trial to evaluate postoperative radiotherapy in renal cell
      carcinoma: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: A meta-analysis was conducted to assess the impact of postoperative
      radiotherapy (PORT) in renal cell carcinoma (RCC) on overall survival (OS),
      disease-free survival (DFS) and locoregional failure (LRF). MATERIALS AND
      METHODS: The Medline, CANCERLIT, Cochrane library database and search engines
      were searched to identify randomized controlled studies comparing radical
      nephrectomy alone with radical nephrectomy followed by PORT for localized RCC.
      Further, radiotherapy techniques and associated side-effects were evaluated.
      RESULTS: Seven controlled trials with a total patient population of 735 were
      identified. Pooled results from these trials showed a significant reduction of
      LRF in patients treated with PORT (P < or = 0.0001). However, there was no
      difference in OS (P = 0.29) and DFS (P = 0.14). The majority of patients was
      treated with larger field sizes with parallel-opposed anteroposterior fields.
      PORT was generally well tolerated; in total, six PORT-related deaths were seen.
      The resultant funnel plot was broader (Egger test P = 0.14) due to low number of
      patients. CONCLUSIONS: PORT significantly reduces LRF but has no effect on OS and
      DFS. However, due to poor patient accrual and older radiotherapy techniques in
      previous studies, there is a need for a new trial to evaluate PORT using
      conformal and intensity-modulated radiotherapy techniques.

PMID- 20139153
TI  - Experience with fulvestrant acetate in castration-resistant prostate cancer
      patients.

PMID- 20139154
TI  - From randomized trial to practice: single institution experience using the GOG
      172 i.p. chemotherapy regimen for ovarian cancer.
AB  - BACKGROUND: The objective of the study was to evaluate completion rates and toxic
      effects of an i.p. chemotherapy regimen in a cross-section of nonselected
      patients with ovarian cancer (OC). PATIENTS AND METHODS: All patients with stage
      IIIC OC consecutively operated at our institution from January 2006 to December
      2007 were prospectively collected and analyzed. RESULTS: Eighty-nine patients
      with stage IIIC OC optimally debulked were evaluated for this study. An i.p. port
      was primarily placed in 53 of 89 (60%), and i.p. chemotherapy was recommended in
      55 patients. Reasons for not recommending i.p. chemotherapy in patients optimally
      debulked included postoperative complications (n = 7: 8%), poor
      nutritional/functional status (n = 5: 6%), and extensive surgery including bowel
      resection (n = 9: 10%). Thirty-three patients (33/55: 60%) recommended to receive
      i.p. chemotherapy-initiated i.p. treatment. Fifty-two percent of those beginning
      i.p. therapy (17/33) received three or more cycles with 36% (12/33) successfully
      completing six cycles. Reasons for discontinuation included grade 3-4
      nephrotoxicity in 3 of 21 (14%), febrile neutropenia/sepsis in 3 of 21 (14%),
      port infection or malfunction in 8 of 21 (38%). CONCLUSIONS: The i.p.
      chemotherapy regimen used in a consecutive cohort of patients carries could be
      completed in only a small percentage of patients. Less toxic regimens with higher
      acceptability should be considered.

PMID- 20139155
TI  - Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves
      prognosis: how much is it true?

PMID- 20139156
TI  - Incidence, patterns of care and prognostic factors for outcome of
      gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the
      National Cancer Registry of Spain (RGETNE).
AB  - BACKGROUND: Neuroendocrine tumors (NETs) are an unusual family of neoplasms with
      a wide and complex spectrum of clinical behavior. Here, we present the first
      report of a National Cancer Registry of gastroenteropancreatic neuroendocrine
      tumors from a Southern European country. PATIENTS AND METHODS: Data was provided
      online at www.retegep.net by participating centers and assessed for internal
      consistency by external independent reviewers. RESULTS: The study cohort
      comprised 907 tumors. The most common tumor types were carcinoids (55%),
      pancreatic nonfunctional tumors (20%), metastatic NETs of unknown primary (9%),
      insulinomas (8%) and gastrinomas (4%). Forty-four percent presented with distant
      disease at diagnosis, most often those from small intestine (65%), colon (48%),
      rectum (40%) and pancreas (38%), being most unusual in appendix primaries (1.3%).
      Stage at diagnosis varied significantly according to sex, localization of primary
      tumor, tumor type and grade. Overall 5-year survival was 75.4% (95% confidence
      interval 71.3% to 79.5%) and was significantly greater in women, younger patients
      and patients with hormonal syndrome and early stage or lower grade tumors.
      Prognosis also differed according to tumor type and primary tumor site. However,
      stage and Ki-67 index were the only independent predictors for survival.
      CONCLUSION: This national database reveals relevant information regarding
      epidemiology, current clinical practices and prognosis of NETs in Spain,
      providing valuable insights that may contribute to understand regional
      disparities in the incidence, patterns of care and survival of this heterogeneous
      disease across different continents and countries.

PMID- 20139157
TI  - Coming to a decision about cochlear implantation: parents making choices for
      their deaf children.
AB  - This study combined quantitative and qualitative methods in a sequential approach
      to investigate the experiences of parents making decisions about cochlear
      implants for their deaf children. Quantitative findings from a survey instrument
      completed by 247 parents were extended and elaborated by qualitative findings
      from in-depth interviews with 27 of the survey respondents. Although parents used
      a variety of information sources when considering an implant, cochlear implant
      centers and doctors comprised their major source of information. Most parents
      found the decision-making process difficult and stressful, but a proportion
      reported finding the decision easy, believing that there was no other option for
      their child, and were keen for implantation to proceed as soon as possible.
      Implications for professionals working with families are discussed.

PMID- 20139158
TI  - A peroxidase contributes to ROS production during Arabidopsis root response to
      potassium deficiency.
AB  - Reactive oxygen species (ROS) play an important role in root responses to
      potassium deprivation by regulating the expression of the high-affinity K(+)
      transporter gene AtHAK5 and other genes. Activation-tagged lines of Arabidopsis
      plants containing the AtHAK5 promoter driving luciferase were screened for
      bioluminescence under potassium-sufficient conditions. A member of the type III
      peroxidase family, RCI3, was isolated and when it was overexpressed by the
      activation tag, this led to the enhanced expression of luciferase and the
      endogenous AtHAK5. RCI3 was found to be up-regulated upon potassium deprivation.
      Plants overexpressing RCI3 (RCI3-ox) showed more ROS production and AtHAK5
      expression whereas the ROS production and AtHAK5 expression were reduced in rci3
      1 under K(+)-deprived conditions. These results suggested that RCI3 is involved
      in the production of ROS under potassium deprivation and that RCI3-mediated ROS
      production affects the regulation of AtHAK5 expression. This peroxidase appears
      to be another component of the low-potassium signal transduction pathway in
      Arabidopsis roots.

PMID- 20139159
TI  - Regulation of sulfate uptake and assimilation--the same or not the same?
AB  - Plant take up the essential nutrient sulfur as sulfate from the soil, reduce it,
      and assimilate into bioorganic compounds, with cysteine being the first product.
      Both sulfate uptake and assimilation are highly regulated by the demand for the
      reduced sulfur, by availability of nutrients, and by environmental conditions. In
      the last decade, great progress has been achieved in dissecting the regulation of
      sulfur metabolism. Sulfate uptake and reduction of activated sulfate, adenosine
      5'-phosphosulfate (APS), to sulfite by APS reductase appear to be the key
      regulatory steps. Here, we review the current knowledge on regulation of these
      processes, with special attention given to similarities and differences.

PMID- 20139160
TI  - Structure of a heterotetrameric geranyl pyrophosphate synthase from mint (Mentha
      piperita) reveals intersubunit regulation.
AB  - Terpenes (isoprenoids), derived from isoprenyl pyrophosphates, are versatile
      natural compounds that act as metabolism mediators, plant volatiles, and
      ecological communicators. Divergent evolution of homomeric prenyltransferases
      (PTSs) has allowed PTSs to optimize their active-site pockets to achieve
      catalytic fidelity and diversity. Little is known about heteromeric PTSs,
      particularly the mechanisms regulating formation of specific products. Here, we
      report the crystal structure of the (LSU . SSU)(2)-type (LSU/SSU = large/small
      subunit) heterotetrameric geranyl pyrophosphate synthase (GPPS) from mint (Mentha
      piperita). The LSU and SSU of mint GPPS are responsible for catalysis and
      regulation, respectively, and this SSU lacks the essential catalytic amino acid
      residues found in LSU and other PTSs. Whereas no activity was detected for
      individually expressed LSU or SSU, the intact (LSU . SSU)(2) tetramer produced
      not only C(10)-GPP at the beginning of the reaction but also C(20)-GGPP
      (geranylgeranyl pyrophosphate) at longer reaction times. The activity for
      synthesizing C(10)-GPP and C(20)-GGPP, but not C(15)-farnesyl pyrophosphate,
      reflects a conserved active-site structure of the LSU and the closely related
      mustard (Sinapis alba) homodimeric GGPPS. Furthermore, using a genetic
      complementation system, we showed that no C(20)-GGPP is produced by the mint GPPS
      in vivo. Presumably through protein-protein interactions, the SSU remodels the
      active-site cavity of LSU for synthesizing C(10)-GPP, the precursor of volatile
      C(10)-monoterpenes.

PMID- 20139161
TI  - Embryo and endosperm inherit distinct chromatin and transcriptional states from
      the female gametes in Arabidopsis.
AB  - Whether deposited maternal products are important during early seed development
      in flowering plants remains controversial. Here, we show that RNA interference
      mediated downregulation of transcription is deleterious to endosperm development
      but does not block zygotic divisions. Furthermore, we show that RNA POLYMERASE II
      is less active in the embryo than in the endosperm. This dimorphic pattern is
      established late during female gametogenesis and is inherited by the two products
      of fertilization. This juxtaposition of distinct transcriptional activities
      correlates with differential patterns of histone H3 lysine 9 dimethylation, LIKE
      HETEROCHROMATIN PROTEIN1 localization, and Histone H2B turnover in the egg cell
      versus the central cell. Thus, distinct epigenetic and transcriptional patterns
      in the embryo and endosperm are already established in their gametic progenitors.
      We further demonstrate that the non-CG DNA methyltransferase CHROMOMETHYLASE3
      (CMT3) and DEMETER-LIKE DNA glycosylases are required for the correct
      distribution of H3K9 dimethylation in the egg and central cells, respectively,
      and that plants defective for CMT3 activity show abnormal embryo development. Our
      results provide evidence that cell-specific mechanisms lead to the
      differentiation of epigenetically distinct female gametes in Arabidopsis
      thaliana. They also suggest that the establishment of a quiescent state in the
      zygote may play a role in the reprogramming of the young plant embryo.

PMID- 20139162
TI  - SLOW MOTION is required for within-plant auxin homeostasis and normal timing of
      lateral organ initiation at the shoot meristem in Arabidopsis.
AB  - The regular arrangement of leaves and flowers around a plant's stem is a
      fascinating expression of biological pattern formation. Based on current models,
      the spacing of lateral shoot organs is determined by transient local auxin maxima
      generated by polar auxin transport, with existing primordia draining auxin from
      their vicinity to restrict organ formation close by. It is unclear whether this
      mechanism encodes not only spatial information but also temporal information
      about the plastochron (i.e., the interval between the formation of successive
      primordia). Here, we identify the Arabidopsis thaliana F-box protein SLOW MOTION
      (SLOMO) as being required for a normal plastochron. SLOMO interacts genetically
      with components of polar auxin transport, and mutant shoot apices contain less
      free auxin. However, this reduced auxin level at the shoot apex is not due to
      increased polar auxin transport down the stem, suggesting that it results from
      reduced synthesis. Independently reducing the free auxin level in plants causes a
      similar lengthening of the plastochron as seen in slomo mutants, suggesting that
      the reduced auxin level in slomo mutant shoot apices delays the establishment of
      the next auxin maximum. SLOMO acts independently of other plastochron regulators,
      such as ALTERED MERISTEM PROGRAM1 or KLUH/CYP78A5. We propose that SLOMO
      contributes to auxin homeostasis in the shoot meristem, thus ensuring a normal
      rate of the formation of auxin maxima and organ initiation.

PMID- 20139164
TI  - Mother knows best: maternal influence on early embryogenesis.

PMID- 20139163
TI  - The Arabidopsis rcn1-1 mutation impairs dephosphorylation of Phot2, resulting in
      enhanced blue light responses.
AB  - Phototropins (phot) sense blue light through the two N-terminal chromophore
      binding LOV domains and activate the C-terminal kinase domain. The resulting
      phototropin autophosphorylation is essential for biological activity. We
      identified the A1 subunit of Ser/Thr protein phosphatase 2A (PP2A) as interacting
      with full-length phot2 in yeast and also interacting with phot2 in an in vitro
      protein binding assay. Phenotypic characterizations of a phot1-5 rcn1-1 (for root
      curling in n-naphthylphthalamic acid1) double mutant, in which phot2 is the only
      functional phototropin and PP2A activity is reduced, showed enhanced phototropic
      sensitivity and enhanced blue light-induced stomatal opening, suggesting that
      PP2A activity is involved in regulating phot2 function. When treated with
      cantharidin, a chemical inhibitor of PP2A, the phot1-5 mutant exhibited enhanced
      phot2-mediated phototropic responses like those of the phot1-5 rcn1-1 double
      mutant. Immunoblot analysis to examine phot2 endogenous phosphorylation levels
      and in vitro phosphorylation assays of phot2 extracted from plants during dark
      recovery from blue light exposure confirmed that phot2 is more slowly
      dephosphorylated in the reduced PP2A activity background than in the wild-type
      PP2A background, suggesting that phosphorylated phot2 is a substrate of PP2A
      activity. While reduced PP2A activity enhanced the activity of phot2, it did not
      enhance either phot1 dephosphorylation or the activity of phot1 in mediating
      phototropism or stomatal opening.

PMID- 20139165
TI  - Functional characterization of cytochrome P450 2A6 allelic variants CYP2A6*15,
      CYP2A6*16, CYP2A6*21, and CYP2A6*22.
AB  - Variation in CYP2A6 levels and activity can be attributed to genetic polymorphism
      and, thus, functional characterization of allelic variants is necessary to define
      the importance of CYP2A6 polymorphism in humans. The aim of the present study was
      to investigate the reported alleles CYP2A6*15, CYP2A6*16, CYP2A6*21, and
      CYP2A6*22, in terms of the functional consequences of their mutations on the
      enzyme catalytic activity. With use of the wild-type CYP2A6 cDNA as template,
      site-directed mutagenesis was performed to introduce nucleotide changes encoding
      K194E substitution in CYP2A6*15, R203S substitution in CYP2A6*16, K476R
      substitution in CYP2A6*21, and concurrent D158E and L160I substitutions in
      CYP2A6*22. Upon sequence verification, the CYP2A6 wild-type and mutant constructs
      were individually coexpressed with NADPH-cytochrome P450 reductase in Escherichia
      coli. A kinetic study using a coumarin 7-hydroxylase assay indicated that
      CYP2A6*15 exhibited higher V(max) than the wild type, whereas all mutant
      constructs, except for variant CYP2A6*16, exhibited higher K(m) values. Analysis
      of the V(max)/K(m) ratio revealed that all mutants demonstrated 0.85- to 1.05
      fold differences from the wild type, with the exception of variant CYP2A6*22,
      which only portrayed 39% of the wild-type intrinsic clearance. These data
      suggested that individuals carrying the CYP2A6*22 allele are likely to have lower
      metabolism of CYP2A6 substrate than individuals expressing CYP2A6*15, CYP2A6*16,
      CYP2A6*21, and the wild type.

PMID- 20139166
TI  - An important role of increase in tetrahydrobiopterin via H2O2-JAK2 signalling
      pathway in late phase of ischaemic preconditioning.
AB  - The goal of this study was to elucidate whether there is an increase in
      myocardial tetrahydrobiopterin (BH4), which is a cofactor for nitric oxide
      synthase, during the late phase of ischaemic preconditioning (IPC) leading to
      cardioprotection against myocardial infarction and, if so, to examine the
      induction mechanisms of BH4 synthesis. Rats were preconditioned with four cycles
      of 3 min left main coronary artery (LCA) occlusion followed by 10 min
      reperfusion. Twenty-four hours later, the rats were subjected to 20 min ischaemia
      by LCA ligation and 2 h reperfusion, and the infarct size was determined by 2,3,5
      triphenyltetrazolium chloride staining. The IPC protocol reduced the infarct
      size, and increased the BH4 content and expression of GTP-cyclohydrolase I
      (GTPCH), which is the rate-limiting enzyme for BH4 synthesis. Administration of a
      GTPCH inhibitor attenuated both the reduction in infarct size and the increase in
      BH4 levels. Moreover, the increase in BH4 content was reduced by administration
      of catalase or a Janus tyrosine kinase-2 (JAK2) inhibitor. These observations
      suggest that upregulation of BH4 synthesis in the heart contributes to an
      acquisition of ischaemic tolerance in late IPC, and the increase in myocardial
      BH4 content seems to be mediated by the induction of GTPCH via the H(2)O(2)-JAK2
      pathway.

PMID- 20139167
TI  - Branched fibres in old dystrophic mdx muscle are associated with mechanical
      weakening of the sarcolemma, abnormal Ca2+ transients and a breakdown of Ca2+
      homeostasis during fatigue.
AB  - In the dystrophinopathies, skeletal muscle fibres undergo cycles of degeneration
      and regeneration, with regenerated fibres displaying a branched morphology. This
      study tests the hypothesis that regenerated branched fibres are mechanically
      weakened by the presence of branches and are damaged by contractions which do not
      affect unbranched dystrophin-negative fibres. Experiments were carried out on
      single fast-twitch fibres and whole muscle from the dystrophin-negative mdx
      mouse. Fura-2 was ionophoresed into fibres to measure intracellular Ca(2+)
      concentration ([Ca(2+)](i)). Single branched mdx fibres have abnormal Ca(2+)
      kinetics, with the [Ca(2+)](i) transient at the peak of the twitch depressed, are
      damaged by fatiguing activation, resulting in a breakdown of Ca(2+) homeostasis,
      and break at branch points when submaximally activated in skinned fibre
      experiments. When old intact isolated mdx muscles, with >90% branched fibres, are
      eccentrically activated with a moderate eccentric protocol there is a 40 +/- 8%
      reduction in maximal force. Isolated single fibres from these muscles show areas
      of damage at fibre branch points. This same eccentric protocol causes no force
      loss in either littermate control muscles or mdx muscles with <10% branched
      fibres. I present a two-stage hypothesis for muscle damage in the
      dystrophinopathies, as follows: stage 1, the absence of dystrophin disrupts ion
      channel function, causing an activation of necrotizing Ca(2+)-activated
      proteases, which results in regenerated branched fibres; and stage 2, branched
      fibres are mechanically damaged during contraction. These results may have
      implications when considering therapies for boys with Duchenne muscular
      dystrophy. In particular, any therapy aimed at rescuing the defective gene will
      presumably have to do so before the number of branched fibres has increased to a
      level where the muscle is mechanically compromised.

PMID- 20139168
TI  - Aerobic exercise acutely improves insulin- and insulin-like growth factor-1
      mediated vasorelaxation in hypertensive rats.
AB  - Limited information is available concerning the effects of aerobic exercise on
      vasorelaxation in hypertension. The aim of this study was to investigate the
      effects of a single bout of aerobic exercise on insulin- and insulin-like growth
      factor-1 (IGF-1)-induced vasorelaxation in hypertensive rats. Four-month-old
      spontaneously hypertensive rats were randomly divided into a sedentary group
      (SHR) and an exercise group (SHR+Ex) subjected to a single bout of aerobic
      exercise conducted by treadmill running at 21 m min(1) for 1 h. Age-matched
      Wistar-Kyoto rats were used as a normotensive control group (WKY). Insulin- and
      IGF-1-induced vasorelaxant responses in the three groups were evaluated by using
      isolated aortic rings, with or without endothelial denudation, in organ baths.
      Possible roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase
      (NOS) involved in the NO-dependent vasorelaxation were examined by adding
      selective inhibitors. The role of superoxide was also clarified by adding
      superoxide dismutase (SOD). In addition, the endothelium-independent vascular
      responses to sodium nitroprusside (SNP), a NO donor, were examined. The insulin-
      and IGF-1-induced vasorelaxation was significantly (P < 0.05) decreased in the
      SHR group compared with the WKY group. This decreased response in SHR was
      improved by exercise. These vasorelaxant responses among the three groups became
      similar after endothelial denudation and pretreatment with the PI3K inhibitor,
      NOS inhibitor or SOD. Also, no difference among groups was found in the SNP
      induced vasorelaxation. We concluded that a single bout of aerobic exercise
      acutely improves insulin- and IGF-1-mediated vasorelaxation in an endothelium
      dependent manner in hypertensive rats.

PMID- 20139169
TI  - Exercise training attenuates ageing-induced BKCa channel downregulation in rat
      coronary arteries.
AB  - Physical inactivity and ageing are widely recognized as risk factors for
      development of coronary artery disease. One of the characteristic changes that
      occurs in aged coronary artery is downregulation of their large-conductance
      voltage- and calcium-activated K(+) (BK(Ca)) channels. In this study, we
      investigated the effects of moderate exercise training (ET) on the activity of
      BK(Ca) channels in coronary arteries of aged rats. Old Fischer 344 rats (23-26
      months old) were randomly assigned to sedentary (O-SED, n = 24) or exercise
      trained groups (O-ET, n = 28). The O-ET rats underwent a progressive treadmill
      exercise-training programme for 60 min day(1), 5 days week(1) for 12 weeks. Young
      animals were used for comparison. Coronary arteries were mounted on a wire
      myograph, and contractions in response to 1, 10, 30, 50 and 100 nmoll(1)
      iberiotoxin were compared. Iberiotoxin (100 nmol l(1)) contracted coronary
      arteries of young, O-SED and O-ET rats by 115 +/- 14, 36 +/- 5.6 and 61 +/- 5% of
      5-hydroxytryptamine-induced contractions, respectively. Patch-clamp studies
      revealed a larger magnitude of BK(Ca) current in young (104 +/- 15.6 pA pF(1))
      compared with O-ET (44 +/- 9 pA pF(1)) and least in O-SED coronary smooth muscle
      cells (8.6 +/- 2 pA pF(1)). Western immunoblotting was performed to study
      expression levels of BK(Ca) channel proteins. The alpha and beta1 subunits of the
      BK(Ca) channel were reduced by 40 +/- 3.5 and 30 +/- 2.6%, respectively, in
      coronary arteries of old compared with young rats, and ET attenuated this
      reduction in expression level to 28 +/- 2 and 12 +/- 4%, respectively. Our
      results showed that ageing was associated with a reduction in BK(Ca) channels,
      and ET partly reversed this reduction. We conclude that low-intensity ET may be
      beneficial in restoring age-related decline in coronary vasodilatory properties
      mediated by BK(Ca) channels.

PMID- 20139170
TI  - Anti-vascular endothelial growth factor therapies and cardiovascular toxicity:
      what are the important clinical markers to target?
AB  - BACKGROUND: Therapies targeting vascular endothelial growth factor (VEGF) are
      associated with hypertension, cardiotoxicity, and thromboembolic events. METHODS:
      All prospective phase I-III clinical trials published up to December 2008 of
      approved anti-VEGF therapies (bevacizumab, sunitinib, sorafenib) and relevant
      literature were reviewed. RESULTS: The rates of Common Toxicity Criteria (version
      3) grade 3-4 hypertension with bevacizumab, sunitinib, and sorafenib were 9.2%,
      6.9%, and 7.2%, respectively. Grade 3-4 left ventricular systolic dysfunction was
      noted in 0.3%, 1.4%, and 0.05% of patients, respectively, whereas the rates of
      grade 3-4 thromboembolism were 9.6%, 1.2%, and 3.8%, respectively. The renin
      angiotensin-aldosterone system (RAAS) may play a key role in vasoconstriction and
      capillary rarefaction, which are unleashed when VEGF signaling is targeted.
      Inhibiting RAAS may be the optimal approach for managing these toxicities.
      CONCLUSIONS: In anticipation of cardiovascular complications with anti-VEGF
      therapies, early detection and personalized management may improve clinical
      outcomes and tolerance.

PMID- 20139171
TI  - Extensive rearrangement of the Arabidopsis mitochondrial genome elicits cellular
      conditions for thermotolerance.
AB  - Three nuclear genes involved in plant mitochondrial recombination surveillance
      have been previously identified. Simultaneous disruption of two of these genes,
      MutS Homolog1 (MSH1) and RECA3, results in extensive rearrangement of the
      mitochondrial genome and dramatic changes in plant growth. We have capitalized on
      these changes in mitochondrial genome organization to understand the role
      mitochondria play in plant cellular and developmental processes. Transcript
      profiling of the double mutants grown under normal conditions revealed
      differential regulation of numerous nuclear genes involved in stress responses
      together with increased levels of polyadenylated mitochondrial transcripts. We
      show that extensive rearrangement of the mitochondrial genome in Arabidopsis
      (Arabidopsis thaliana) directly elicits physiological stress responses in plants,
      with msh1 recA3 double mutants exhibiting enhanced thermotolerance. Likewise, we
      show that mitochondrial transcriptional changes are associated with genome
      recombination, so that differential gene modulation is accomplished, at least in
      part, through altered gene copy number.

PMID- 20139172
TI  - GITR engagement preferentially enhances proliferation of functionally competent
      CD4+CD25+FoxP3+ regulatory T cells.
AB  - Naturally occurring regulatory T cells (Treg) express high levels of
      glucocorticoid-induced tumour necrosis factor receptor (GITR). However, studies
      of the role of GITR in Treg biology has been complicated by the observation that
      upon activation effector CD4(+) T (Teff) cells also express the receptor. Here,
      we dissect the contribution of GITR-induced signaling networks in the expansion
      and function of FoxP3(+) Treg. We demonstrate that a high-affinity soluble Fc
      GITR-L dimer, in conjugation with alphaCD3, specifically enhances in vitro
      proliferation of Treg, which retain their phenotypic markers (CD25 and FoxP3) and
      their suppressor function, while minimally affecting Teff cells. Furthermore, Fc
      GITR-L does not impair Teff susceptibility to suppression, as judged by
      cocultures employing GITR-deficient and GITR-sufficient CD4(+) T-cell subsets.
      Notably, this expansion of Treg could also be seen in vivo, by injecting FoxP3
      IRES-GFP mice with Fc-GITR-L even in the absence of antigenic stimulation. In
      order to test the efficacy of these findings therapeutically, we made use of a
      C3H/HeJ hemophilia B-prone mouse model. The use of liver-targeted human
      coagulation factor IX (hF.IX) gene therapy in this model has been shown to induce
      liver toxicity and the subsequent failure of hF.IX expression. Interestingly,
      injection of Fc-GITR-L into the hemophilia-prone mice that were undergoing liver
      targeted hF.IX gene therapy increased the expression of F.IX and reduced the
      anticoagulation factors. We conclude that GITR engagement enhances Treg
      proliferation both in vitro and in vivo and that Fc-GITR-L may be a useful tool
      for in vivo tolerance induction.

PMID- 20139173
TI  - Molecular analysis of IgD-positive human germinal centres.
AB  - It is controversially discussed whether human IgM(+)IgD(+)CD27(+) B cells, which
      carry somatically mutated Ig variable region (IgV) genes, are derived from
      germinal centres (GC) B cells or originate from another developmental pathway. GC
      composed of IgM(+)IgD(+) B cells, which co-express the CD70 surface marker, have
      been described in approximately 10% of tonsils. As IgM(+)IgD(+)CD27(+) B cells
      might be generated in such GC, we characterized IgD(+) tonsillar GC cells. GC
      dominated by IgD(+) B cells were present in 10 of 67 tonsils analyzed. Three GC
      were additionally positive for CD70. Detailed analysis of one such GC by
      microdissection and single-cell DNA PCR revealed IgD(+) GC B cells undergoing
      somatic hypermutation during clonal expansion. However, further analysis of this
      GC as well as five additional microdissected GC by reverse transcription (RT)-PCR
      for clonally related Igmu and Igdelta transcripts indicated that the B-cell
      clones in five of these six IgD(+) GC belong to the IgD-only B cell subset, which
      has deleted the Cmu gene, and that only one GC harboured a large IgM(+)IgD(+) B
      cell clone. Hence, most IgD(+) GC consist of IgD-only B cells and fully developed
      IgM(+)IgD(+)(CD70(+)) GC are very rare. This indicates that the rare IgM(+)IgD(+)
      GC B-cell clones from IgD(+) GC contribute little to the large population of
      IgM(+)IgD(+)CD27(+) B cells. Finally, an RT-PCR analysis with clone-specific
      primers for two IgD(+) GC B-cell clones showed an absence of IgG or IgA class
      switched clone members, indicating strict regulation of class switching and a
      selective production of IgD(+) B cells from such clones.

PMID- 20139174
TI  - Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in
      mice.
AB  - CD4(+)CD25(+) regulatory T (Treg) cells cause immune suppression by inhibiting T
      cell effector functions and play pivotal roles not only in self-tolerance but
      also in immune response to parasitic microbial pathogens. Mycobacteria are major
      parasitic bacterial pathogens, but the role of CD4(+)CD25(+) Treg cells in
      mycobacterial infection is not yet defined. In this study we found that, at the
      early stage of infection, depletion of CD25(+) cells reduced both bacterial load
      and granuloma formation in mice infected with Mycobacterium tuberculosis strains,
      such as M. tuberculosis Erdman or M. tuberculosis Kurono. However, at a later
      stage of infection, bacterial burden and histopathology were similar regardless
      of depletion of CD25(+) cells. Severe combined immunodeficient (SCID) mice
      reconstituted with CD4(+)CD25(-) T cells alone or a combination of CD4(+)CD25(+)
      and CD4(+)CD25(-) T cells showed similar bacterial loads and survival kinetics
      after infection with M. tuberculosis Erdman. Consistent with in vivo data, in
      vitro studies revealed that mycobacterial antigens, purified protein derivative
      of tuberculin (PPD), failed to induce the suppressive function of CD4(+)CD25(+)
      Treg cells to CD4(+)CD25(-) effector T cells, as demonstrated by the lack of
      response of CD4(+)CD25(+) T cells to PPD, in mice chronically infected with
      Mycobacterium bovis bacillus Calmette-Guerin and M. tuberculosis. Our data show
      that CD4(+)CD25(+) Treg cells have a transient effect at the early stage of
      mycobacterial infection but, contrary to the expectation, have little impact on
      the overall course of infection.

PMID- 20139175
TI  - The study of B cells and antibodies in Japan: a historical perspective.
AB  - Japanese scientists were involved in pioneering work on therapeutic antisera and
      have made huge contributions to the characterization of the antibody molecules
      that are responsible for this and many other biological activities, as well as
      working back to understand the B cells that produce these Igs. This review
      emphasizes the role of Japanese immunologists in this field, starting with their
      work in developing antisera and studying the structure of Igs. It describes the
      molecular mechanisms that generate the enormous antibody repertoire and regulate
      B-cell development and signaling. It also details the importance of the germinal
      center in generating B-cell memory and the terminal differentiation of B cells as
      antibody-secreting plasma cells.

PMID- 20139176
TI  - Inflammatory stimulation and hypoxia cooperatively activate HIF-1{alpha} in
      bronchial epithelial cells: involvement of PI3K and NF-{kappa}B.
AB  - The transcription factor hypoxia-inducible factor (HIF)-1 plays a central
      physiological role in oxygen and energy homeostasis, and is activated during
      hypoxia by stabilization of the subunit HIF-1alpha. Recent studies have
      demonstrated that non-hypoxic stimuli can also activate HIF-1alpha in a cell
      specific manner. Here, we demonstrate that stimulation of BEAS-2B cells and
      primary human bronchial epithelial cells by proinflammatory cytokines TNFalpha/IL
      4 strongly induced expression and transcriptional activity of HIF-1alpha under
      normoxic conditions and amplified hypoxic HIF-1alpha activation. TNFalpha/IL-4
      stimulated de novo HIF-1alpha gene transcription and translation rather than
      affected HIF-1alpha protein degradation and mRNA decay process. The activation of
      HIF-1alpha by TNFalpha/IL-4 was countered by the phosphoinositol 3-kinase (PI3K)
      inhibitor LY-294002 and rapamycin, an antagonist of mammalian target of rapamycin
      (mTOR), but not by inhibition of the MAPK pathway. In line, TNFalpha/IL-4 also
      activated NF-kappaB, whereas blocking of NF-kappaB by an inhibitor or silencing
      NF-kappaB subunit p65 attenuated HIF-1alpha activation by TNFalpha/IL-4. We also
      found the collaborative induction of VEGF, a potent angiogenic factor required
      for airway remodeling, by TNFalpha/IL-4 and hypoxia partially via HIF-1alpha
      pathway in BEAS-2B cells. This study reports the previously unsuspected
      collaborative regulation of HIF-1alpha by TNFalpha/IL-4 and hypoxia in bronchial
      epithelial cells partially via PI3K-mTOR and NF-kappaB pathway, and thereby will
      lead to the elucidation of the importance of HIF-1 in integrating inflammatory
      and hypoxic response in the pathogenesis of airway diseases.

PMID- 20139177
TI  - Reduction of collagen VII anchoring fibrils in the airway basement membrane zone
      of infant rhesus monkeys exposed to house dust mite.
AB  - Collagen VII anchoring fibrils in the basement membrane zone (BMZ) are part of a
      supracellular anchoring network that attaches the epithelium to the BMZ.
      Sloughing of airway epithelium in asthmatics (creola bodies) is a pathology
      associated with the supracellular anchoring network. In a rhesus monkey model of
      house dust mite (HDM)-induced allergic asthma, we found increased deposition of
      collagen I in the BMZ. In this study, we determine whether HDM also affected
      deposition of collagen VII in the BMZ. In the developing airway of rhesus
      monkeys, the width of collagen VII anchoring fibrils in the BMZ was 0.02 +/- 0.04
      microm at 1 mo of age. At 6 mo the width had increased to 1.28 +/- 0.34 microm
      and at 12 mo 2.15 +/- 0.13 microm. In animals treated with HDM, we found a 42.2%
      reduction in the width of collagen VII layer in the BMZ at 6 mo (0.74 +/- 0.15
      microm; P < 0.05). During recovery, the rate of collagen VII deposition returned
      to normal. However, the amount of collagen VII lost was not recovered after 6 mo.
      We concluded that normal development of the collagen VII attachment between the
      epithelium and BMZ occurs in coordination with development of the BMZ. However,
      in HDM-treated animals, the collagen VII attachment with the epithelium was
      significantly reduced. Such a reduction in collagen VII may weaken the
      supracellular anchoring network and be associated with sloughing of the
      epithelium and formation of creola bodies in asthmatics.

PMID- 20139178
TI  - Upregulation of Oct-4 isoforms in pulmonary artery smooth muscle cells from
      patients with pulmonary arterial hypertension.
AB  - Oct-4 is a transcription factor considered to be one of the defining pluripotency
      markers in embryonic stem cells. Its expression has also been demonstrated in
      adult stem cells, tumorigenic cells, and, most recently and controversially, in
      somatic cells. Oct-4 pseudogenes also contribute to carcinogenesis. Oct-4 may be
      involved in the excessive proliferation of pulmonary arterial smooth muscle cells
      (PASMC) in patients with idiopathic pulmonary arterial hypertension (IPAH),
      contributing to the pathogenesis of IPAH. In this study, we show that Oct-4
      isoforms are upregulated in IPAH-PASMC. Human embryonic stem cells (H9 line) and
      human PASMC from normotensive subjects were used throughout the investigation as
      positive and negative controls. In addition to significant upregulation of Oct-4
      in a population of IPAH-PASMC, HIF-2alpha, a hypoxia-inducible transcription
      factor that has been shown to bind to the Oct-4 promoter and induces its
      expression and transcriptional activity, was also increased. Interestingly, a
      substantial upregulation of Oct-4 isoforms and HIF-2alpha was also observed in
      normal PASMC exposed to chronic hypoxia. In conclusion, the data suggest that
      both Oct-4 isoforms are upregulated and potentially have a significant role in
      the development of vascular abnormalities associated with the pathogenesis of
      IPAH and in pulmonary hypertension triggered by chronic hypoxia.

PMID- 20139179
TI  - Hyperoxia inhibits protein synthesis and increases eIF2alpha phosphorylation in
      the newborn rat lung.
AB  - Prolonged exposure to hyperoxia contributes to aberrant lung growth in premature
      infants. Of the deleterious effects induced by hyperoxia, alterations in protein
      synthesis are likely to be of great importance to the developing lung. Regulation
      of mRNA translation occurs predominantly at the level of initiation via control
      of mRNA/ribosome binding by proteins known as eukaryotic initiation factors
      (eIF). Although hyperoxia is known to suppress mRNA translation in adult lungs,
      little is known regarding the effects in newborns or the involved mechanism. This
      study was performed to determine the effect of exposure to 95% O(2) on pulmonary
      protein synthesis in 4-day-old Sprague-Dawley rat pups. We found that hyperoxia
      suppressed the incorporation of [(3)H]phenylalanine into lung protein over time,
      resulting in a 23% reduction after 72 h compared with pups reared in room air.
      This effect was preceded by a shift in total lung RNA to lower order polysomes.
      Hyperoxia increased eIF4G-eIF4E binding, a surrogate maker of eIF4F complex
      assembly, and initially activated, then suppressed, the phosphorylation of
      ribosomal S6 kinase 1 and ribosomal S6 protein, downstream targets of mammalian
      target of rapamycin. Exposure to 95% O(2) enhanced the phosphorylation of the
      translational repressor eIF2alpha in whole lung extracts and the immunoreactivity
      of phosphorylated eIF2alpha in epithelial cells. Cell culture studies further
      demonstrated that hyperoxia increases eIF2alpha phosphorylation in lung
      epithelial cells, but not in lung fibroblasts. These findings illustrate that
      hyperoxia-induced suppression of mRNA translation in the newborn lung is
      accompanied by increased phosphorylation of eIF2alpha in the epithelium.

PMID- 20139180
TI  - Mechanisms for lung function impairment and airway hyperresponsiveness following
      chronic hypoxia in rats.
AB  - Although chronic normobaric hypoxia (CH) alters lung function, its potential to
      induce bronchial hyperreactivity (BHR) is still controversial. Thus the effects
      of CH on airway and tissue mechanics separately and changes in lung
      responsiveness to methacholine (MCh) were investigated. To clarify the
      mechanisms, mechanical changes were related to end-expiratory lung volume (EELV),
      in vivo results were compared with those in vitro, and lung histology was
      assessed. EELV was measured plethysmographically in two groups of rats exposed to
      21 days of CH (11% O(2)) or to normoxia. Total respiratory impedance was measured
      under baseline conditions and following intravenous MCh challenges (2-18 microg x
      kg(-1) x min(-1)). The lungs were then excised and perfused, and the pulmonary
      input impedance was measured, while MCh provocations were repeated under a
      pulmonary capillary pressure of 5, 10, and 15 mmHg. Airway resistance, tissue
      damping, and elastance were extracted from the respiratory impedance and
      pulmonary input impedance spectra. The increases in EELV following CH were
      associated with decreases in airway resistance, whereas tissue damping and
      elastance remained unaffected. CH led to the development of severe BHR to MCh
      (206 +/- 30 vs. 95 +/- 24%, P < 0.001), which was not detectable when the same
      lungs were studied in vitro at any pulmonary capillary pressure levels
      maintained. Histology revealed pulmonary arterial vascular remodeling with
      overexpression of alpha-smooth muscle actin antibody in the bronchial wall. These
      findings suggest that, despite the counterbalancing effect of the increased EELV,
      BHR develops following CH, only in the presence of intact autonomous nervous
      system. Thus neural control plays a major role in the changes in the basal lung
      mechanics and responsiveness following CH.

PMID- 20139181
TI  - Hypoxia-induced proliferation of human pulmonary microvascular endothelial cells
      depends on epidermal growth factor receptor tyrosine kinase activation.
AB  - We hypothesized that hypoxia would activate epidermal growth factor receptor
      (EGFR) tyrosine kinase, leading to increased arginase expression and resulting in
      proliferation of human pulmonary microvascular endothelial cell (hPMVEC). To test
      this hypothesis, hPMVEC were incubated in normoxia (20% O(2), 5% CO(2)) or
      hypoxia (1% O(2), 5% CO(2)). Immunoblotting for EGFR and proliferating cell
      nuclear antigen was done, and protein levels of both total EGFR and proliferating
      cell nuclear antigen were greater in hypoxic hPMVEC than in normoxic hPMVEC.
      Furthermore, hypoxic hPMVEC had greater levels of EGFR activity than did normoxic
      hPMVEC. Hypoxic hPMVEC had a twofold greater level of proliferation compared with
      normoxic controls, and this increase in proliferation was prevented by the
      addition of AG-1478 (a pharmacological inhibitor of EGFR). Immunoblotting for
      arginase I and arginase II demonstrated a threefold induction in arginase II
      protein levels in hypoxia, with little change in arginase I protein levels. The
      hypoxic induction of arginase II protein was prevented by treatment with AG-1478.
      Proliferation assays were performed in the presence of arginase inhibitors, and
      hypoxia-induced proliferation was also prevented by arginase inhibition. Finally,
      treatment with an EGFR small interfering RNA prevented hypoxia-induced
      proliferation and urea production. These findings demonstrate that hypoxia
      activates EGFR tyrosine kinase, leading to arginase expression and thereby
      promoting proliferation in hPMVEC.

PMID- 20139182
TI  - The N-acetylmuramic acid 6-phosphate etherase gene promotes growth and cell
      differentiation of cyanobacteria under light-limiting conditions.
AB  - Inactivation of sll0861 in Synechocystis sp. strain PCC 6803 or the homologous
      gene alr2432 in Anabaena sp. strain PCC 7120 had no effect on the growth of these
      organisms at a light intensity of 30 micromol photons m(-2) s(-1) but reduced
      their growth at a light intensity of 5 or 10 micromol photons m(-2) s(-1). In
      Anabaena, inactivation of the gene also significantly reduced the rate of
      heterocyst differentiation under low-light conditions. The predicted products of
      sll0861 and alr2432 and homologs of these genes showed similarity to N
      acetylmuramic acid 6-phosphate etherase (MurQ), an enzyme involved in
      peptidoglycan recycling, in Escherichia coli. E. coli murQ and the cyanobacterial
      homologs could functionally substitute for each other. We hypothesize that murQ
      in cyanobacteria promotes low-light adaptation through reutilization of
      peptidoglycan degradation products.

PMID- 20139183
TI  - Genome sequence of Streptococcus gallolyticus: insights into its adaptation to
      the bovine rumen and its ability to cause endocarditis.
AB  - Streptococcus gallolyticus (formerly known as Streptococcus bovis biotype I) is
      an increasing cause of endocarditis among streptococci and frequently associated
      with colon cancer. S. gallolyticus is part of the rumen flora but also a cause of
      disease in ruminants as well as in birds. Here we report the complete nucleotide
      sequence of strain UCN34, responsible for endocarditis in a patient also
      suffering from colon cancer. Analysis of the 2,239 proteins encoded by its 2,350
      kb-long genome revealed unique features among streptococci, probably related to
      its adaptation to the rumen environment and its capacity to cause endocarditis.
      S. gallolyticus has the capacity to use a broad range of carbohydrates of plant
      origin, in particular to degrade polysaccharides derived from the plant cell
      wall. Its genome encodes a large repertoire of transporters and catalytic
      activities, like tannase, phenolic compounds decarboxylase, and bile salt
      hydrolase, that should contribute to the detoxification of the gut environment.
      Furthermore, S. gallolyticus synthesizes all 20 amino acids and more vitamins
      than any other sequenced Streptococcus species. Many of the genes encoding these
      specific functions were likely acquired by lateral gene transfer from other
      bacterial species present in the rumen. The surface properties of strain UCN34
      may also contribute to its virulence. A polysaccharide capsule might be
      implicated in resistance to innate immunity defenses, and glucan
      mucopolysaccharides, three types of pili, and collagen binding proteins may play
      a role in adhesion to tissues in the course of endocarditis.

PMID- 20139184
TI  - Role of the DinB homologs Rv1537 and Rv3056 in Mycobacterium tuberculosis.
AB  - The environment encountered by Mycobacterium tuberculosis during infection is
      genotoxic. Most bacteria tolerate DNA damage by engaging specialized DNA
      polymerases that catalyze translesion synthesis (TLS) across sites of damage. M.
      tuberculosis possesses two putative members of the DinB class of Y-family DNA
      polymerases, DinB1 (Rv1537) and DinB2 (Rv3056); however, their role in damage
      tolerance, mutagenesis, and survival is unknown. Here, both dinB1 and dinB2 are
      shown to be expressed in vitro in a growth phase-dependent manner, with dinB2
      levels 12- to 40-fold higher than those of dinB1. Yeast two-hybrid analyses
      revealed that DinB1, but not DinB2, interacts with the beta-clamp, consistent
      with its canonical C-terminal beta-binding motif. However, knockout of dinB1,
      dinB2, or both had no effect on the susceptibility of M. tuberculosis to
      compounds that form N(2)-dG adducts and alkylating agents. Similarly, deletion of
      these genes individually or in combination did not affect the rate of spontaneous
      mutation to rifampin resistance or the spectrum of resistance-conferring rpoB
      mutations and had no impact on growth or survival in human or mouse macrophages
      or in mice. Moreover, neither gene conferred a mutator phenotype when expressed
      ectopically in Mycobacterium smegmatis. The lack of the effect of altering the
      complements or expression levels of dinB1 and/or dinB2 under conditions predicted
      to be phenotypically revealing suggests that the DinB homologs from M.
      tuberculosis do not behave like their counterparts from other organisms.

PMID- 20139185
TI  - Characterization of a mannose utilization system in Bacillus subtilis.
AB  - The mannose operon of Bacillus subtilis consists of three genes, manP, manA, and
      yjdF, which are responsible for the transport and utilization of mannose.
      Upstream and in the same orientation as the mannose operon a regulatory gene,
      manR, codes for a transcription activator of the mannose operon, as shown in this
      study. Both mannose operon transcription and manR transcription are inducible by
      mannose. The presence of mannose resulted in a 4- to 7-fold increase in
      expression of lacZ from the manP promoter (P(manP)) and in a 3-fold increase in
      expression of lacZ from the manR promoter (P(manR)). The transcription start
      sites of manPA-yjdF and manR were determined to be a single A residue and a
      single G residue, respectively, preceded by -10 and -35 boxes resembling a
      vegetative sigma(A) promoter structure. Through deletion analysis the target
      sequences of ManR upstream of P(manP) and P(manR) were identified between bp -80
      and -35 with respect to the transcriptional start site of both promoters.
      Deletion of manP (mannose transporter) resulted in constitutive expression from
      both the P(manP) and P(manR) promoters, indicating that the phosphotransferase
      system (PTS) component EII(Man) has a negative effect on regulation of the
      mannose operon and manR. Moreover, both P(manP) and P(manR) are subject to carbon
      catabolite repression (CCR). By constructing protein sequence alignments a DNA
      binding motif at the N-terminal end, two PTS regulation domains (PRDs), and an
      EIIA- and EIIB-like domain were identified in the ManR sequence, indicating that
      ManR is a PRD-containing transcription activator. Like findings for other PRD
      regulators, the phosphoenolpyruvate (PEP)-dependent phosphorylation by the
      histidine protein HPr via His15 plays an essential role in transcriptional
      activation of P(manP) and P(manR). Phosphorylation of Ser46 of HPr or of the
      homologous Crh protein by HPr kinase and formation of a repressor complex with
      CcpA are parts of the B. subtilis CCR system. Only in the double mutant with an
      HPr Ser46Ala mutation and a crh knockout mutation was CCR strongly reduced. In
      contrast, P(manR) and P(manP) were not inducible in a ccpA deletion mutant.

PMID- 20139186
TI  - Genetic modification of the Salmonella membrane physical state alters the pattern
      of heat shock response.
AB  - It is now recognized that membranes are not simple physical barriers but
      represent a complex and dynamic environment that affects membrane protein
      structures and their functions. Recent data emphasize the role of membranes in
      sensing temperature changes, and it has been shown that the physical state of the
      plasma membrane influences the expression of a variety of genes such as heat
      shock genes. It has been widely shown that minor alterations in lipid membranes
      are critically involved in the conversion of signals from the environment to the
      transcriptional activation of heat shock genes. Previously, we have proposed that
      the composition, molecular arrangement, and physical state of lipid membranes and
      their organization have crucial roles in cellular responses during stress caused
      by physical and chemical factors as well as in pathological states. Here, we show
      that transformation of Salmonella enterica serovar Typhimurium LT2 (Salmonella
      Typhimurium) with a heterologous Delta(12)-desaturase (or with its trans-membrane
      regions) causes major changes in the pathogen's membrane dynamic. In addition,
      this pathogen is strongly impaired in the synthesis of major stress proteins
      (heat shock proteins) under heat shock. These data support the hypothesis that
      the perception of temperature in Salmonella is strictly controlled by membrane
      order and by a specific membrane lipid/protein ratio that ultimately causes
      transcriptional activation of heat shock genes. These results represent a
      previously unrecognized mode of sensing temperature variation used by this
      pathogen at the onset of infection.

PMID- 20139187
TI  - Global regulation of food supply by Pseudomonas putida DOT-T1E.
AB  - Pseudomonas putida DOT-T1E was used as a model to develop a "phenomics" platform
      to investigate the ability of P. putida to grow using different carbon, nitrogen,
      and sulfur sources and in the presence of stress molecules. Results for growth of
      wild-type DOT-T1E on 90 different carbon sources revealed the existence of a
      number of previously uncharted catabolic pathways for compounds such as
      salicylate, quinate, phenylethanol, gallate, and hexanoate, among others.
      Subsequent screening on the subset of compounds on which wild-type DOT-TIE could
      grow with four knockout strains in the global regulatory genes Deltacrc,
      Deltacrp, DeltacyoB, and DeltaptsN allowed analysis of the global response to
      nutrient supply and stress. The data revealed that most global regulator mutants
      could grow in a wide variety of substrates, indicating that metabolic fluxes are
      physiologically balanced. It was found that the Crc mutant did not differ much
      from the wild-type regarding the use of carbon sources. However, certain pathways
      are under the preferential control of one global regulator, i.e., metabolism of
      succinate and d-fructose is influenced by CyoB, and l-arginine is influenced by
      PtsN. Other pathways can be influenced by more than one global regulator; i.e., l
      valine catabolism can be influenced by CyoB and Crp (cyclic AMP receptor protein)
      while phenylethylamine is affected by Crp, CyoB, and PtsN. These results
      emphasize the cross talk required in order to ensure proper growth and survival.
      With respect to N sources, DOT-T1E can use a wide variety of inorganic and
      organic nitrogen sources. As with the carbon sources, more than one global
      regulator affected growth with some nitrogen sources; for instance, growth with
      nucleotides, dipeptides, d-amino acids, and ethanolamine is influenced by Crp,
      CyoB, and PtsN. A surprising finding was that the Crp mutant was unable to
      flourish on ammonium. Results for assayed sulfur sources revealed that CyoB
      controls multiple points in methionine/cysteine catabolism while PtsN and Crc are
      needed for N-acetyl-l-cysteamine utilization. Growth of global regulator mutants
      was also influenced by stressors of different types (antibiotics, oxidative
      agents, and metals). Overall and in combination with results for growth in the
      presence of various stressors, these phenomics assays provide multifaceted
      insights into the complex decision-making process involved in nutrient supply,
      optimization, and survival.

PMID- 20139188
TI  - Analyses of the regulatory mechanism and physiological roles of Pseudomonas
      aeruginosa OhrR, a transcription regulator and a sensor of organic
      hydroperoxides.
AB  - ohrR encodes an organic hydroperoxide sensor and a transcriptional repressor that
      regulates organic hydroperoxide-inducible expression of a thiol peroxidase gene,
      ohr, and itself. OhrR binds directly to the operators and represses transcription
      of these genes. Exposure to an organic hydroperoxide leads to oxidation of OhrR
      and to subsequent structural changes that result in the loss of the repressor's
      ability to bind to the operators that allow expression of the target genes.
      Differential induction of ohrR and ohr by tert-butyl hydroperoxide suggests that
      factors such as the repressor's dissociation constants for different operators
      and the chemical nature of the inducer contribute to OhrR-dependent organic
      hydroperoxide-inducible gene expression. ohrR and ohr mutants show increased and
      decreased resistance to organic hydroproxides, respectively, compared to a
      parental strain. Moreover, the ohrR mutant had a reduced-virulence phenotype in
      the Pseudomonas aeruginosa-Caenorhabditis elegans pathogenicity model.

PMID- 20139189
TI  - Myxococcus xanthus viability depends on groEL supplied by either of two genes,
      but the paralogs have different functions during heat shock, predation, and
      development.
AB  - Myxococcus xanthus DK1622 contains two paralogous groEL gene loci that possess
      both different sequences and different organizations within the genome. Deletion
      of either one of these two genes alone does not affect cell viability. However,
      deletion of both groEL genes results in cell death unless a complemented groEL1
      or groEL2 gene is present. The groEL1 gene was determined to be essential for
      cell survival under heat shock conditions; a strain with mutant groEL2 caused
      cells to be more sensitive than the wild-type strain to higher temperatures.
      Mutants with a single deletion of either groEL1 (MXAN_4895) or groEL2 (MXAN_4467)
      had a growth curve similar to that of the wild-type strain DK1622 in medium
      containing hydrolyzed proteins as the substrate. However, when cells were
      cultured on medium containing either Escherichia coli cells or casein as the
      substrate, deletion of groEL2, but not groEL1, led to a deficiency in cell
      predation and macromolecular feeding. Furthermore, groEL1 was found to play an
      indispensable role in the development and sporulation of cells, but deletion of
      groEL2 had no visible effects. Our results suggest that, although alternatively
      required for cell viability, the products of the two groEL genes have divergent
      functions in the multicellular social life cycle of M. xanthus DK1622.

PMID- 20139190
TI  - Relevance of DNA alkylation damage repair systems in Salmonella enterica
      virulence.
AB  - Systematic inactivation of pathways involved in DNA alkylation damage repair
      demonstrated that inactivation of the ada, ogt, tag, uvrA, and mfd genes is
      required to detect a Salmonella enterica virulence decrease. Furthermore, the
      fitness of S. enterica, defective in these genes, is lowered only when the
      bacterium is orally, but not intraperitoneally, inoculated.

PMID- 20139191
TI  - Increased expression of the type IV secretion system in piliated Neisseria
      gonorrhoeae variants.
AB  - Neisseria gonorrhoeae produces a type IV secretion system that secretes
      chromosomal DNA. The secreted DNA is active in the transformation of other
      gonococci in the population and may act to transfer antibiotic resistance genes
      and variant alleles for surface antigens, as well as other genes. We observed
      that gonococcal variants that produced type IV pili secreted more DNA than
      variants that were nonpiliated, suggesting that the process may be regulated.
      Using microarray analysis, we found that a piliated strain showed increased
      expression of the gene for the putative type IV secretion coupling protein TraD,
      whereas a nonpiliated variant showed increased expression of genes for
      transcriptional and translational machinery, consistent with its higher growth
      rate compared to that of the piliated strain. These results suggested that type
      IV secretion might be controlled by either traD expression or growth rate. A
      mutant with a deletion in traD was found to be deficient in DNA secretion.
      Further mutation and complementation analysis indicated that traD is
      transcriptionally and translationally coupled to traI, which encodes the type IV
      secretion relaxase. We were able to increase DNA secretion in a nonpiliated
      strain by inserting a gene cassette with a strong promoter to drive the
      expression of the putative operon containing traI and traD. Together, these data
      suggest a model in which the type IV secretion system apparatus is made
      constitutively, while its activity is controlled through regulation of traD and
      traI.

PMID- 20139192
TI  - Effects of sequential Campylobacter jejuni 81-176 lipooligosaccharide core
      truncations on biofilm formation, stress survival, and pathogenesis.
AB  - Campylobacter jejuni is a highly prevalent human pathogen for which pathogenic
      and stress survival strategies remain relatively poorly understood. We previously
      found that a C. jejuni strain 81-176 mutant defective for key virulence and
      stress survival attributes was also hyper-biofilm and hyperreactive to the UV
      fluorescent dye calcofluor white (CFW). We hypothesized that screening for CFW
      hyperreactive mutants would identify additional genes required for C. jejuni
      pathogenesis properties. Surprisingly, two such mutants harbored lesions in
      lipooligosaccharide (LOS) genes (waaF and lgtF), indicating a complete loss of
      the LOS outer core region. We utilized this as an opportunity to explore the role
      of each LOS core-specific moiety in the pathogenesis and stress survival of this
      strain and thus also constructed DeltagalT and DeltacstII mutants with more minor
      LOS truncations. Interestingly, we found that mutants lacking the LOS outer core
      (DeltawaaF and DeltalgtF but not DeltagalT or DeltacstII mutants) exhibited
      enhanced biofilm formation. The presence of the complete outer core was also
      necessary for resistance to complement-mediated killing. In contrast, any LOS
      truncation, even that of the terminal sialic acid (DeltacstII), resulted in
      diminished resistance to polymyxin B. The cathelicidin LL-37 was found to be
      active against C. jejuni, with the LOS mutants exhibiting modest but tiled
      alterations in LL-37 sensitivity. The DeltawaaF mutant but not the other LOS
      mutant strains also exhibited a defect in intraepithelial cell survival, an
      aspect of C. jejuni pathogenesis that has only recently begun to be clarified.
      Finally, using a mouse competition model, we now provide the first direct
      evidence for the importance of the C. jejuni LOS in host colonization.
      Collectively, this study has uncovered novel roles for the C. jejuni LOS,
      highlights the dynamic nature of the C. jejuni cell envelope, and provides
      insight into the contribution of specific LOS core moieties to stress survival
      and pathogenesis.

PMID- 20139193
TI  - Changes in membrane fluid state and heat shock response cause attenuation of
      virulence.
AB  - So far attenuation of pathogens has been mainly obtained by chemical or heat
      treatment of microbial pathogens. Recently, live attenuated strains have been
      produced by genetic modification. We have previously demonstrated that in several
      prokaryotes as well as in yeasts and mammalian cells the heat shock response is
      controlled by the membrane physical state (MPS). We have also shown that in
      Salmonella enterica serovar Typhimurium LT2 (Salmonella Typhimurium)
      overexpression of a Delta(12)-desaturase gene alters the MPS, inducing a sharp
      impairment of transcription of major heat shock genes and failure of the pathogen
      to grow inside macrophage (MPhi) (A. Porta et al., J. Bacteriol. 192:1988-1998,
      2010). Here, we show that overexpression of a homologous Delta(9)-desaturase
      sequence in the highly virulent G217B strain of the human fungal pathogen
      Histoplasma capsulatum causes loss of its ability to survive and persist within
      murine MPhi along with the impairment of the heat shock response. When the
      attenuated strain of H. capsulatum was injected in a mouse model of infection, it
      did not cause disease. Further, treated mice were protected when challenged with
      the virulent fungal parental strain. Attenuation of virulence in MPhi of two
      evolutionarily distant pathogens was obtained by genetic modification of the MPS,
      suggesting that this is a new method that may be used to produce attenuation or
      loss of virulence in both other intracellular prokaryotic and eukaryotic
      pathogens. This new procedure to generate attenuated forms of pathogens may be
      used eventually to produce a novel class of vaccines based on the genetic
      manipulation of a pathogen's membrane fluid state and stress response.

PMID- 20139194
TI  - Delayed papillary muscle rupture following repair of post-infarction ventricular
      septal defect.
AB  - Ventricular septal defect (VSD) and papillary muscle rupture are severe
      complications of myocardial infarction which are usually observed individually
      although their simultaneous occurrence has been observed in pathological studies.
      An 82-year-old female underwent repair of a post-infarction VSD and 13 days later
      required mitral valve replacement due to delayed papillary muscle rupture.
      Mechanical complications of myocardial infarction can occur in the same patient
      even in delayed fashion and a two-stage correction may be successfully
      accomplished.

PMID- 20139195
TI  - Acute and late obstruction of a modified Blalock-Taussig shunt: a two-center
      experience in different catheter-based methods of treatment.
AB  - Modified Blalock-Taussig (B-T) shunt occlusion results in a sudden reduction of
      pulmonary vascular perfusion, causing dramatic saturation drop and cyanosis which
      pose a direct hazard to a child's life. The results of percutaneous local r-tpa
      infusion, balloon angioplasty and additionally stent implantation in obstructed
      modified B-T shunts were studied to assess their role as an alternative to a re
      do surgery. We outline two pediatric centers' experience (period 2004-2008)
      regarding the effectiveness of various emergency treatment methods for occlusion
      or critical stenosis of systemic-to-pulmonary arterial shunts in 23 children.
      Local r-tpa infusion via catheter was performed in 12/23 patients, balloon
      angioplasty in 22/23 and additionally stent implantation in 3/23 children.
      Procedures were successful in 22/23 patients (96%), with an increase in arterial
      saturation [average: 30%; standard deviation (S.D.) 15%; Shapiro-Wilk test;
      dependent t-test-P<0.01]. Unrestricted contrast flow was achieved in 18 patients,
      reduced central flow in three and minimal flow in one child. Neither local nor
      systemic complications occurred. Our experience demonstrates the possibility of
      successful early shunt recanalization with the use of local thrombolytic therapy
      combined with the balloon angioplasty. The presence of old fixed thrombus with
      neointimal hypertrophy in the shunt constitutes an indication for endovascular
      stent implantation.

PMID- 20139196
TI  - Echocardiographic analysis with a two-dimensional strain of chronic myocardial
      ischemia induced with ameroid constrictor in the pig.
AB  - Despite much progress in the medical management of myocardial ischemia, several
      problems remain and experimental models help to improve our understanding of the
      pathophysiology involved in this domain. The ameroid constrictor model is the
      most widely used to create ischemia but evaluation of patent ischemia is still
      under debate. In the present study, we describe the potential of a two
      dimensional (2D) strain for experimentally evaluating myocardial ischemia in the
      pig. An ameroid constrictor was placed around the circumflex artery in 30 pigs.
      Angiography showed 90% stenosis at one and two months. Left ventricular function
      was moderately altered and associated with mitral valve insufficiency in 30% of
      cases. Longitudinal and circumference strains were dramatically modified in the
      ischemic inferior-lateral zone compared to the healthy anterior zone (P<0.01) at
      one and two months. We correlated these results to myocardial ischemia by using
      contrast echocardiography, which showed a significant reduction in myocardial
      perfusion in the ischemic zone compared to the uninjured area, and by using
      histological analysis. We showed that evaluation of the 2D strain could be an
      interesting approach for assessing myocardial ischemia after ameroid constrictor
      implantation. The 2D strain represents a useful tool for the evaluation of
      experimental models of myocardial ischemia.

PMID- 20139197
TI  - Stake through the chest.
AB  - We present a fascinating case of major penetrating trauma to the chest which
      resulted in a successful outcome. Often such trauma is associated with a poor
      outcome due to injury to the heart, lungs or major blood vessels with subsequent
      massive blood loss, pnuemothorax or haemo-pneumothorax. Late complications
      include infection rarely mediastinitis, empyema and occasionally chylothorax from
      damage to the thoracic duct.

PMID- 20139198
TI  - Extracorporeal membrane oxygenation for intraoperative cardiac support in
      children with congenital heart disease.
AB  - OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is commonly used in
      children to allow recovery from ischemic injury or cardiac surgery, to support
      the circulation in case of end-stage cardiomyopathy, as bridge-to-bridge therapy
      and as bridge to transplantation as well. It has achieved success in providing
      cardiac support for these kind of patients with expected mortality due to severe
      myocardial dysfunction. In this modern era, ECMO support should be considered an
      important option for children with cardiopulmonary failure refractory to medical
      therapy or resuscitation. We report our experience in pediatric patients
      supported by ECMO for intraoperative cardiac failure between November 1991 and
      December 2006. METHODS AND RESULTS: Sixty-six patients with a mean age of 5.2+/-4
      years (range: 1 day-17 years) and mean weight of 14.3+/-11 kg (range: 2.8-69 kg)
      had intraoperative ECMO support for failure to wean off cardiopulmonary bypass
      (n=46, 69.7%), low cardiac output syndrome (n=8, 12.1%), isolated right
      ventricular failure (n=6, 9.1%), isolated left ventricular failure (n=3, 4.5%),
      malignant arrhythmia (n=1, 1.5%) and pulmonary hypertension (n=2, 3.1%). Mean
      duration of ECMO support was 5.1+/-3 days. Overall 30 (45.4%) patients were
      successfully weaned off ECMO and survived to decannulation. Overall 6 (9.1%)
      patients were successfully bridged to heart transplantation while on ECMO
      support. Thirty patients died (54.4%) (16 while on ECMO and 14 after
      decannulation) because of multi-factorial complications, i.e. cerebral
      hemorrhage, pulmonary failure, consumption coagulopathy and therapy-resistant
      myocardial insufficiency, leding to an overall hospital mortality rate of 45.4%.
      Mean survival time after decannulation was 28+/-16 h. Overall survival rate on
      ECMO as bridge to recovery and transplantation has been 54.5% with successful
      hospital discharge of patients. CONCLUSIONS: Our experience shows that ECMO
      support can be offered intraoperatively to any children after palliative or
      corrective surgery for congenital heart disease with potentially reversible
      pulmonary, cardiac or cardiopulmonary failure. In the majority of patients who
      did not survive late after weaning from ECMO support, significant myocardial
      dysfunction persisted or pulmonary hypertensive events. Nevertheless, an
      acceptable proportion of patients who were successfully weaned from ECMO
      ultimately survived to leave the hospital.

PMID- 20139199
TI  - Postconditioning in mouse hearts is inhibited by blocking the reverse mode of the
      sodium-calcium exchanger.
AB  - Ischemic postconditioning and inhibition of the reverse mode of the sodium
      calcium exchanger (NCX) are both cardioprotective. We hypothesized that a
      combination of these techniques might have an additive effect mediated by protein
      kinases (see below). Isolated perfused mouse hearts were subjected to 35 min of
      ischemia and 60 min of reperfusion. Each series had its own control ischemia
      group, the other groups were postconditioning with three cycles of 10 s of
      reperfusion and 10 s of ischemia immediately after sustained ischemia; the
      vehicle of the NCX blocker KB-R7943 was added to the perfusate 5 min before
      ischemia in series 1; KB-R7943 was added to the perfusate 5 min before ischemia
      with and without postconditioning in series 2; KB-R7943 was added to the
      perfusate for 5 min from the start of reperfusion with and without
      postconditioning in series 3. Infarct size was measured and cardiac function was
      evaluated. Phosphorylation of AKT, ERK1/2, PKCdelta and PKCepsilon was measured
      by immunoblotting. Postconditioning alone reduced infarct size by 37% and
      activated AKT (P=0.02). Blockade of NCX reduced infarct size when applied before
      ischemia (29%) and at start of reperfusion (32%). Combining NCX blockade with
      postconditioning abolished cardioprotection despite phosphorylation of ERK1/2
      (P=0.03) and PKCepsilon (P=0.01).

PMID- 20139200
TI  - Inflammatory myofibroblastic tumour of the lung in a five-year-old girl.
AB  - The inflammatory myofibroblastic tumour of the lung is considered a rare
      diagnosis of lung masses. We report the case of a five-year-old girl who
      presented with recurrent pyrexia, dry cough, and shortness of breath. Chest X-ray
      and computed tomography showed a total atelectasis of the left lower lobe and a
      segmental atelectasis of the left upper lobe. The mass was removed in toto,
      histopathology revealed the diagnosis of an inflammatory myofibroblastic tumour
      of the lung. The patient is without any signs of relapse 30 months after surgery.

PMID- 20139201
TI  - In patients with cardiac injuries caused by sewing needles is the surgical
      approach the recommended treatment?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: 'In patients with sewing needle cardiac
      injuries is the surgical approach the recommended treatment?' The scientific
      literature was reviewed by searching Medline, using Ovid interface, from 1950 to
      August 2009. Six hundred and twenty-six papers were found, of which 24 were
      deemed relevant to this topic. The authors, journal, date and country of
      publication, patient group studied, study type, relevant outcomes and results of
      these papers were tabulated. The cause of injury may delay the timing of
      presentation the diagnosis and consequently the therapeutic strategy. In nearly
      all the cases in the reviewed papers the authors surgically removed the needle
      from the heart. However, out of the 24 papers, four patients had a conservative
      treatment. Most of the authors recommend early removal of the needle to prevent
      migration and further anatomical damage. The early surgical removal of foreign
      bodies in the heart is considered an effective approach to prevent complications.
      The heart is more vulnerable to serious injuries when the foreign body is
      extracardiac than when the foreign body is completely intracardiac. The unceasing
      motion of the heart against the sharp point of the fixed foreign body will result
      in repetitive wounding with bleeding and consequent cardiac tamponade. Due to the
      tendency of the needle to migrate, the preoperative use of computer tomography
      scan, trans-thoracic and trans-oesophageal echocardiography have been advocated
      to locate the exact position of the needle and its correlation with the
      surrounding tissues. The intraoperative use of epicardial ultrasound or
      fluoroscopy is also recommended. However, in cases of late diagnosis, in
      previously untreated patients, treatment can be individualized. If the symptoms
      are less severe it is reasonable to adopt a conservative approach as with time
      most foreign bodies become safely encysted and do no harm. Patients can remain
      asymptomatic for many years. However, they may present many years later with
      complications such as pericarditis, tamponade or endocarditis. Strict follow-up
      is useful in those patients.

PMID- 20139202
TI  - Minimally invasive left-heart decompression during venoarterial extracorporeal
      membrane oxygenation: an alternative to a percutaneous approach.
AB  - Decompression of the left-heart following initiation of extracorporeal membrane
      oxygenation, is at times required. In the setting of a closed chest this can
      present a challenge. We present a minimally invasive approach to left-heart
      decompression in an adult-sized patient, where a percutaneous option was not
      feasible.

PMID- 20139203
TI  - Recurrent chest wall abscesses overlying a pneumonectomy scar: an unusual
      presentation of a cholecystocutaneous fistula.
AB  - We report a case of recurrent chest wall abscesses overlying a right thoracotomy
      scar four years after a pneumonectomy for a right middle lobe bronchus squamous
      cell carcinoma. Exploration of the abscess cavities revealed no intra-thoracic or
      intra-abdominal communication. The patient developed sinuses in his thoracotomy
      scar and two years later, two gallstones were expelled from these sinuses. A
      cholecystocutaneous fistula was confirmed on a fistulogram.

PMID- 20139204
TI  - Use of the world wide web by cardiac surgery patients.
AB  - Internet use has expanded globally over the last 10 years. The aim of this study
      was to determine the extent that cardiac patients researched their forthcoming
      procedures using the internet and to determine their perception of reliability.
      Sixty-eight consecutive cardiac patients (51 men, median age 67 years) were
      surveyed on their frequency of internet use, whether they used the internet to
      research their operation and how reliable they regarded the information found.
      Forty-two patients had access to the internet, 29 patients used the web on a
      regular basis but 33 reported that they never used the web. Fourteen patients
      used the internet to research their operation themselves. Patients <65 years were
      over twice as likely to have internet access (P<0.0001). However, the use of the
      internet to do research is low irrespective of age (P=0.28). Forty-five patients
      felt that information found on the internet was reliable. Despite a general
      increase in internet access, there is still low usage amongst cardiac patients to
      research their operation. Patients do, however, have confidence in what is
      available on-line. Patient education by the multi-disciplinary team before
      surgery remains of paramount importance.

PMID- 20139205
TI  - Successful surgical repair for Emery-Dreifuss muscular dystrophy valvular disease
      with long-term follow-up.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked muscular dystrophy in
      which cardiac involvement can be serious. The disease progresses rapidly and the
      prognosis is strongly associated with cardiac involvement. We present the case of
      a 49-year-old man who was admitted with shortness of breath. Echocardiography
      revealed a huge right atrium and severe tricuspid regurgitation caused by annular
      dilatation and destruction of leaflets and chordae by pacemaker leads. Tricuspid
      valve replacement, right atrial plication and implantation of epicardial
      pacemaker leads were performed. The patient is in a good condition seven years
      after surgery. Cardiac transplantation is the desired therapy for valvular
      disease in EDMD cardiomyopathy, but this case indicates that valve replacement is
      also acceptable if performed with the appropriate timing.

PMID- 20139208
TI  - GMC strikes off GP who arranged late abortion for her daughter.

PMID- 20139213
TI  - Presentation, pattern, and natural course of severe symptoms, and role of
      antibiotics and antibiotic resistance among patients presenting with suspected
      uncomplicated urinary tract infection in primary care: observational study.
AB  - OBJECTIVE: To assess the natural course and the important predictors of severe
      symptoms in urinary tract infection and the effect of antibiotics and antibiotic
      resistance. DESIGN: Observational study. SETTING: Primary care. PARTICIPANTS: 839
      non-pregnant adult women aged 18-70 presenting with suspected urinary tract
      infection. MAIN OUTCOME MEASURE: Duration and severity of symptoms. RESULTS: 684
      women provided some information on symptoms; 511 had both laboratory results and
      complete symptom diaries. For women with infections sensitive to antibiotics,
      severe symptoms, rated as a moderately bad problem or worse, lasted 3.32 days on
      average. After adjustment for other predictors, moderately bad symptoms lasted
      56% longer (incidence rate ratio 1.56, 95% confidence interval 1.22 to 1.99,
      P<0.001) in women with resistant infections; 62% longer (1.62, 1.13 to 2.31,
      P=0.008) when no antibiotics prescribed; and 33% longer (1.33, 1.14 to 1.56,
      P<0.001) in women with urethral syndrome. The duration of symptoms was shorter if
      the doctor was perceived to be positive about diagnosis and prognosis (continuous
      7 point scale: 0.91, 0.84 to 0.99; P=0.021) and longer when the woman had
      frequent somatic symptoms (1.03, 1.01 to 1.05, P=0.002; for each symptom), a
      history of cystitis, urinary frequency, and more severe symptoms at baseline.
      CONCLUSION: Antibiotic resistance and not prescribing antibiotics are associated
      with a greater than 50% increase in the duration of more severe symptoms in women
      with uncomplicated urinary tract infection. Women with a history of cystitis,
      frequent somatic symptoms (high somatisation), and severe symptoms at baseline
      can be given realistic advice that they are likely to have severe symptoms
      lasting longer than three days.

PMID- 20139214
TI  - Effectiveness of five different approaches in management of urinary tract
      infection: randomised controlled trial.
AB  - OBJECTIVE: To assess the impact of different management strategies in urinary
      tract infections. DESIGN: Randomised controlled trial. SETTING: Primary care.
      PARTICIPANTS: 309 non-pregnant women aged 18-70 presenting with suspected urinary
      tract infection. INTERVENTION: Patients were randomised to five management
      approaches: empirical antibiotics; empirical delayed (by 48 hours) antibiotics;
      or targeted antibiotics based on a symptom score (two or more of urine
      cloudiness, urine smell, nocturia, or dysuria), a dipstick result (nitrite or
      both leucocytes and blood), or a positive result on midstream urine analysis.
      Self help advice was controlled in each group. MAIN OUTCOME MEASURES: Symptom
      severity (days 2 to 4) and duration, and use of antibiotics. RESULTS: Patients
      had 3.5 days of moderately bad symptoms if they took antibiotics immediately.
      There were no significant differences in duration or severity of symptoms (mean
      frequency of symptoms on a 0 to 6 scale: immediate antibiotics 2.15, midstream
      urine 2.08, dipstick 1.74, symptom score 1.77, delayed antibiotics 2.11;
      likelihood ratio test for the five groups P=0.177). There were differences in
      antibiotic use (immediate antibiotics 97%, midstream urine 81%, dipstick 80%,
      symptom score 90%, delayed antibiotics 77%; P=0.011) and in sending midstream
      urine samples (immediate antibiotics 23%, midstream urine 89%, dipstick 36%,
      symptom score 33%, delayed antibiotics 15%; P<0.001). Patients who waited at
      least 48 hours to start taking antibiotics reconsulted less (hazard ratio 0.57
      (95% confidence interval 0.36 to 0.89), P=0.014) but on average had symptoms for
      37% longer than those taking immediate antibiotics (incident rate ratio 1.37
      (1.11 to 1.68), P=0.003), particularly the midstream urine group (73% longer, 22%
      to 140%; none of the other groups had more than 22% longer duration). CONCLUSION:
      All management strategies achieve similar symptom control. There is no advantage
      in routinely sending midstream urine samples for testing, and antibiotics
      targeted with dipstick tests with a delayed prescription as backup, or empirical
      delayed prescription, can help to reduce antibiotic use. STUDY REGISTRATION:
      National Research Register N0484094184 ISRCTN: 03525333.

PMID- 20139215
TI  - Meta-analysis of individual participant data: rationale, conduct, and reporting.

PMID- 20139216
TI  - Use of venlafaxine compared with other antidepressants and the risk of sudden
      cardiac death or near death: a nested case-control study.
AB  - OBJECTIVE: To assess whether use of the antidepressant venlafaxine is associated
      with an increased risk of sudden cardiac death or near death compared with other
      commonly used antidepressants. DESIGN: Population based observational study.
      SETTING: We did a nested case-control analysis within a new user cohort formed
      using the United Kingdom General Practice Research Database. PARTICIPANTS: New
      users of venlafaxine, fluoxetine, citalopram, or dosulepin on or after 1 January
      1995, aged 18 to 89 years, with a diagnosis of depression or anxiety.
      Participants were followed-up until February 2005, or the occurrence of sudden
      cardiac death or near death, identified from medical records indicating non-fatal
      acute ventricular tachyarrhythmia, sudden death due to cardiac causes, or out of
      hospital deaths from acute ischaemic cardiac events. For each case, 30 controls
      were selected matched for age, sex, calendar time, and indication. We used
      conditional logistic regression to calculate the adjusted odds ratio of sudden
      cardiac death or near death associated with current use of venlafaxine compared
      with current use of fluoxetine, citalopram or dosulepin. RESULTS: 207 384
      participants were followed-up for an average of 3.3 years. There were 568 cases
      of sudden cardiac death or near death, which were matched to 14 812 controls. The
      adjusted odds ratio of sudden cardiac death or near death associated with
      venlafaxine use was 0.66 (95% confidence interval 0.38 to 1.14) relative to
      fluoxetine use, whereas compared with citalopram it was 0.89 (0.50 to 1.60) and
      with dosulepin 0.83 (0.46 to 1.52). CONCLUSIONS: In this large, population based
      study, the use of venlafaxine was not associated with an excess risk of sudden
      cardiac death or near death compared with fluoxetine, dosulepin, or citalopram,
      in patients with depression or anxiety.

PMID- 20139217
TI  - Women's views about management and cause of urinary tract infection: qualitative
      interview study.
AB  - OBJECTIVES: To explore the views of women with urinary tract infection on the
      acceptability of different strategies for managing the infection, including
      delayed use of antibiotics, and the cause of infection. DESIGN: Qualitative
      interview study with semistructured one to one interviews within a randomised
      controlled trial of different management strategies. Analysis drew on some of the
      principles of constant comparison to generate key themes grounded in reported
      experiences and understandings. SETTING: Seven general practices across four
      counties in southern England. PARTICIPANTS: 21 women presenting to general
      practices who were taking part in the larger trial. RESULTS: Women preferred not
      to take antibiotics and were open to alternative management approaches. With a
      strategy of "antibiotic delay" some women felt a lack of validation or that they
      were not listened to by their general practitioner. Women attributed urinary
      tract infection to lifestyle habits and behaviours, such as poor hygiene, general
      "negligence," and even a "penalty of growing old." CONCLUSION: A clear
      acknowledgment of women's triggers to consult is needed. If women are asked to
      delay taking antibiotics, the clinician must address the particular worries that
      women might have and explain the rationale for not using antibiotics immediately.

PMID- 20139218
TI  - Cost effectiveness of management strategies for urinary tract infections: results
      from randomised controlled trial.
AB  - OBJECTIVE: To assess the cost effectiveness of different management strategies
      for urinary tract infections. DESIGN: Cost effectiveness analysis alongside a
      randomised controlled trial with a one month follow-up. SETTING: Primary care.
      PARTICIPANTS: 309 non-pregnant adult women aged 18-70 presenting with suspected
      urinary tract infection. INTERVENTIONS: Patients were randomised to five basic
      management approaches: empirical antibiotics, empirical delayed (by 48 hours)
      antibiotics, or targeted antibiotics based on either a high symptom score (two or
      more of urine cloudiness, smell, nocturia, dysuria), dipstick results (nitrite or
      leucocytes and blood), or receipt of a positive result on midstream urine
      analysis. MAIN OUTCOME MEASURE: Duration of symptoms and cost of care. RESULTS:
      Management with targeted antibiotics with midstream urine analysis was more
      costly over the period of one month. Costs for the midstream urine analysis and
      dipstick management groups were pound37 and pound35, respectively; these compared
      with pound31 for immediate antibiotics. Cost effectiveness acceptability curves
      suggested that if avoiding a day of moderately bad symptoms was valued at less
      than pound10, then immediate antibiotics is likely to be the most cost effective
      strategy. For values over pound10, targeted antibiotics with dipstick testing
      becomes the most cost effective strategy, though because of the uncertainty we
      can never be more than 70% certain that this strategy truly is the most cost
      effective. CONCLUSION: Dipstick testing with targeted antibiotics is likely to be
      cost effective if the value of saving a day of moderately bad symptoms is pound10
      or more, but caution is required given the considerable uncertainty surrounding
      the estimates.

PMID- 20139219
TI  - Venlafaxine and cardiovascular toxicity.

PMID- 20139220
TI  - Urinary tract infection in primary care.

PMID- 20139221
TI  - Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated
      genital diseases in young women.
AB  - BACKGROUND: The impact of the prophylactic vaccine against human papillomavirus
      (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital
      disease was investigated in a population that approximates sexually naive women
      in that they were "negative to 14 HPV types" and in a mixed population of HPV
      exposed and -unexposed women (intention-to-treat group). METHODS: This analysis
      studied 17 622 women aged 15-26 years who were enrolled in one of two randomized,
      placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient
      on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo
      was given at day 1, month 2, and month 6. All women underwent cervicovaginal
      sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months
      thereafter. Outcomes were any cervical intraepithelial neoplasia; any external
      anogenital and vaginal lesions; Pap test abnormalities; and procedures such as
      colposcopy and definitive therapy. Absolute rates are expressed as women with
      endpoint per 100 person-years at risk. RESULTS: The average follow-up was 3.6
      years (maximum of 4.9 years). In the population that was negative to 14 HPV
      types, vaccination was up to 100% effective in reducing the risk of HPV16/18
      related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related
      genital warts. In the intention-to-treat group, vaccination also statistically
      significantly reduced the risk of any high-grade cervical lesions (19.0%
      reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95%
      confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7%
      reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI =
      0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo
      = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3%
      reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI
      = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine =
      1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83),
      irrespective of causal HPV type. CONCLUSIONS: High-coverage HPV vaccination
      programs among adolescents and young women may result in a rapid reduction of
      genital warts, cervical cytological abnormalities, and diagnostic and therapeutic
      procedures. In the longer term, substantial reductions in the rates of cervical,
      vulvar, and vaginal cancers may follow.

PMID- 20139222
TI  - The DMM complex prevents spreading of DNA methylation from transposons to nearby
      genes in Neurospora crassa.
AB  - Transposable elements are common in genomes and must be controlled. Many
      organisms use DNA methylation to silence such selfish DNA, but the mechanisms
      that restrict the methylation to appropriate regions are largely unknown. We
      identified a JmjC domain protein in Neurospora, DNA METHYLATION MODULATOR-1 (DMM
      1), that prevents aberrant spreading of DNA and histone H3K9 methylation from
      inactivated transposons into nearby genes. Mutation of a conserved residue within
      the JmjC Fe(II)-binding site abolished dmm-1 function, as did mutations in
      conserved cysteine-rich domains. Mutants defective only in dmm-1 mutants grow
      poorly, but growth is restored by reduction or elimination of DNA methylation
      using the drug 5-azacytosine or by mutation of the DNA methyltransferase gene dim
      2. DMM-1 relies on an associated protein, DMM-2, which bears a DNA-binding motif,
      for localization and proper function. HP1 is required to recruit the DMM complex
      to the edges of methylated regions.

PMID- 20139223
TI  - Airway wall expression of OX40/OX40L and interleukin-4 in asthma.
AB  - BACKGROUND: The costimulatory molecule OX40 and its ligand, OX40L, mediate key
      aspects of allergic airway inflammation in animal models of asthma, including
      eosinophilic airway inflammation, airway hyperresponsiveness, and T helper 2
      polarization. We sought to examine OX40/OX40L and interleukin (IL)-4 expression
      in asthma across severities. METHODS: Bronchial biopsies were obtained from 27
      subjects with asthma (mild Global Initiative for Asthma [GINA] 1 [n = 10],
      moderate GINA 2-3 [n = 7], and severe GINA 4-5 [n = 10]) and 13 healthy controls.
      The number of OX40(+), OX40L(+), IL-4(+), and IL-4 receptor alpha (IL-4Ralpha)(+)
      cells in the lamina propria and airway smooth muscle (ASM) bundle and the
      intensity of IL-4Ralpha(+) expression by the ASM were assessed. RESULTS: The
      number of OX40(+), OX40L(+), and IL-4(+) cells in the lamina propria and OX40(+)
      and IL-4(+) cells in the ASM bundle was significantly increased in subjects with
      mild asthma, but not in those with moderate or severe asthma, compared with
      healthy controls. In the subjects with asthma, OX40/OX40L expression was
      positively correlated with the number of eosinophils and IL-4(+) cells in the
      lamina propria. The number of IL-4Ralpha(+) cells in the lamina propria was
      significantly increased in moderate-to-severe disease, but not in mild asthma,
      compared with controls. IL-4Ralpha expression by the ASM bundle was not different
      among groups. CONCLUSIONS: OX40/OX40L expression is increased in the bronchial
      submucosa in mild asthma, but not in moderate-to-severe disease, and is related
      to the degree of tissue eosinophilia and IL-4 expression. Whether these
      costimulatory molecules have a role as targets for asthma requires further
      investigation.

PMID- 20139224
TI  - Reversible cardiac dysfunction associated with pandemic 2009 influenza A(H1N1).
AB  - Historical influenza A epidemics have carried elevated rates of cardiovascular
      disease, including transient cardiac dysfunction. Whether such an association
      holds for the novel influenza A strain, pandemic 2009 influenza A(H1N1)
      [A(H1N1)], remains unknown. We report an index case of transient cardiac
      dysfunction associated with A(H1N1) infection. Next, we reviewed 123 sequential
      cases of patients hospitalized with pandemic A(H1N1) at a single academic medical
      center in the United States from April 1, 2009, through October 31, 2009. We
      identified that 4.9% (6/123) of patients had either new or worsened left
      ventricular dysfunction. These cases ranged in age from 23 to 51 years, and all
      had preexisting medical conditions. ICU level care was required in 83% (5/6) of
      the cases. Sixty-seven percent (4/6) of the cases had follow-up echocardiograms,
      and left ventricular function improved in all four. We conclude that potentially
      reversible cardiac dysfunction is a relatively common complication associated
      with hospitalized pandemic A(H1N1) influenza.

PMID- 20139225
TI  - Sleep-disordered breathing in obese children: the southern Italy experience.
AB  - BACKGROUND: The association of obesity with sleep-associated respiratory
      disturbances, which has traditionally been described as a problem in adults,
      actually originates in childhood. We sought an association between sleep
      disordered breathing (SDB) and overweight and/or obesity in a large cohort of
      school- and preschool-aged children in Southern Italy. METHODS: One thousand two
      hundred seven children (612 girls and 595 boys; mean age 7.3 years) were screened
      by self-administered questionnaires. According to answers, subjects were divided
      into three groups: nonsnorers (NS), occasional snorers (OS), and habitual snorers
      (HS). All HS, who also failed an oximetry study at home, underwent
      polysomnographic monitoring for the definition of SDB. BMI was calculated
      according to Italian growth charts. RESULTS: A total of 809 subjects (67.0%) were
      eligible for the study. Of them, 44 subjects (5.4%) were classified as HS, 138
      (17.0%) as OS, and 627 (77.5%) as NS. Fourteen subjects (1.7%) were given a
      diagnosis of obstructive sleep apnea syndrome (OSAS). Sixty-four subjects (7.9%)
      were defined as obese, 121 (14.9%) as overweight, and 624 (77.2%) as normal
      weight. The frequency of HS was significantly higher in obese subjects than in
      overweight and normal-weight subjects (12.5% vs 5.8% vs 4.6%, respectively; P =
      .02), whereas the frequency of OSAS was 1.6% in normal-weight, 1.6% in
      overweight, and 3.1% in obese subjects (P = not significant). CONCLUSIONS: Our
      findings in a large sample of Italian children suggest that obesity is associated
      with snoring.

PMID- 20139226
TI  - Relationship between critical pressure and volume exhaled during negative
      pressure in awake subjects with sleep-disordered breathing.
AB  - BACKGROUND: Critical pressure (Pcrit) is considered a reliable parameter to
      evaluate the mechanical properties of the passive upper airway (UA) and is
      significantly increased in patients with obstructive sleep apnea-hypopnea (OSAH)
      compared with normal subjects. The volume exhaled in the first 0.5 s after
      application at the mouth of 5 cm H(2)O negative pressure at the onset of
      expiration (V,NEP(0.5)) during wakefulness has been used as a marker of UA
      collapsibility. The aim of this study was to investigate if there is a
      significant relationship between V,NEP(0.5) and Pcrit in normal subjects,
      snorers, and patients with OSAH. METHODS: Thirty men, 10 with OSAH (aged 64 +/-
      9.1 years, BMI 32 +/- 4.9 kg/m(2), apnea-hypopnea index [AHI] 43.8 +/- 24, neck
      circumference 46.6 +/- 3.7 cm), 10 snorers (aged 68 +/- 11 years, BMI 26.6 +/-
      4.6 kg/m(2), AHI 3.5 +/- 0.8, snoring time > or = 30% of sleep time, neck
      circumference 42.2 +/- 3.9 cm), and 10 controls (aged 67 +/- 12 years, BMI 25.4
      +/- 2.2 kg/m(2), AHI 1.9 +/- 1.2, neck circumference 41.2 +/- 2.2 cm) underwent
      V,NEP(0.5) measurement in supine position while awake and Pcrit measurement
      during sleep. Correlation between V,NEP(0.5) and Pcrit was performed in all
      subjects. RESULTS: Controls had V,NEP(0.5) of 456 +/- 82 mL and Pcrit of -1.38 +/
      0.6 cm H(2)O, snorers had V,NEP(0.5) of 321 +/- 33 mL and Pcrit -0.55 +/- 0.3 cm
      H(2)O, and patients with OSAH showed V,NEP(0.5) of 295 +/- 67 mL and Pcrit of
      0.99 +/- 1 cm H(2)O (P < .001 vs normal subjects). A strong correlation was found
      between V,NEP(0.5) and Pcrit (r(2) = 0.61, P < .0001). CONCLUSIONS: In males with
      neck circumference > 37 cm, V,NEP(0.5) during wakefulness strongly reflects Pcrit
      in a wide range of values. Our findings suggest that V,NEP(0.5) can be used as
      valuable substitute for Pcrit to assess UA collapsibility for clinical and
      research purposes in these subjects.

PMID- 20139227
TI  - Fluorescence in situ hybridization in the definitive diagnosis of malignant
      mesothelioma in effusion cytology.
AB  - BACKGROUND: Distinction of malignant mesothelioma (MM) from reactive mesothelial
      cells (RM) in effusions is notoriously difficult. The aim of our study was to
      test chromosomal aberrations detected by fluorescence in situ hybridization
      (FISH) in the diagnosis of MM in effusion cytology and to explore the potential
      role of p16, p14, and p15 gene methylation as an alternative mechanism of tumor
      suppressor gene inactivation. METHODS: Fifty-two effusions of biopsy-proven MM
      and 28 benign effusions were retrospectively analyzed by multitarget FISH assay
      for aberrations of chromosomes 3, 7, 17, and 9p21. In case of a negative result,
      the corresponding MM biopsy specimen was analyzed. Methylation-specific
      polymerase chain reaction (MSP) for p16, p14, and p15 was performed on FISH
      negative MM biopsy specimens. RESULTS: Seventy-nine percent of effusions with
      biopsy-proven MM had chromosomal aberrations, with loss of 9p21 as the most
      common finding. All benign effusions were FISH negative. Sensitivity,
      specificity, and positive and negative predictive values for detection of MM by
      FISH were 79%, 100%, 100%, and 72%, respectively. Six of nine FISH-negative
      effusions with biopsy-proven MM were also FISH negative in the MM biopsy
      specimens. Four of five FISH-negative biopsy specimens showed promoter
      methylation in p16 and p14 as compared with one of 12 benign controls.
      CONCLUSIONS: FISH is a sensitive and highly specific method for the definitive
      diagnosis of MM in effusion cytology. In the subset of FISH-negative MM, tumor
      suppressor genes on the chromosomal region 9p21 are often inactivated by promoter
      methylation.

PMID- 20139228
TI  - Risk of COPD from exposure to biomass smoke: a metaanalysis.
AB  - BACKGROUND: Although many studies have suggested that biomass smoke is a risk
      factor for COPD, the relationship between the two has not been firmly
      established. In particular, the extent of the association between exposure of
      biomass smoke and COPD in different populations, as well as the relationship
      between biomass smoke and cigarette smoke, is not clear. To ascertain the
      relationship between biomass smoke and COPD, we performed a metaanalysis.
      METHODS: We searched MEDLINE, EMBASE, and the Latin American and Caribbean
      Literature in Health Sciences Database and analyzed 15 epidemiologic (11 cross
      sectional and four case-control) studies that met our criteria. Data were
      extracted and analyzed independently by two investigators using a standardized
      protocol. RESULTS: Overall, people exposed to biomass smoke have an odds ratio
      (OR) of 2.44 (95% CI, 1.9-3.33) for developing COPD, relative to those not
      exposed to biomass smoke. Biomass smoke exposure was clearly identified as a risk
      factor for developing COPD in both women (OR, 2.73; 95% CI, 2.28-3.28) and men
      (OR, 4.30; 95% CI, 1.85-10.01), and in both the Asian population (OR, 2.31; 95%
      CI, 1.41-3.78) and the non-Asian population (OR, 2.56; 95% CI, 1.71-3.83). This
      risk factor has also been revealed in patients with chronic bronchitis (OR, 2.56;
      95% CI, 1.77-3.70) and COPD (OR, 2.65; 95% CI, 1.75-4.03), and in cigarette
      smokers (OR, 4.39; 95% CI, 1.40-4.66) and non-cigarette smokers (OR, 2.55; 95%
      CI, 2.06-3.15). CONCLUSIONS: Exposure to biomass smoke is a risk factor for COPD.

PMID- 20139229
TI  - Comparison of pleural fluid N-terminal pro-brain natriuretic peptide and brain
      natriuretic-32 peptide levels.
AB  - BACKGROUND: Current evidence indicates that measurement of pleural fluid N
      terminal pro-brain natriuretic peptide (NT-proBNP) levels can aid in
      distinguishing pleural effusions of cardiac origin from those of noncardiac
      origin. To date, only one study, to our knowledge, has described simultaneous
      measurement of pleural fluid brain natriuretic-32 peptide (BNP) and NT-proBNP.
      The purpose of the present study was to determine pleural fluid BNP and NT-proBNP
      levels and analyze the relationship between these two measurements. We
      hypothesized that there would be a positive correlation between pleural fluid NT
      proBNP and BNP, whereas NT-proBNP levels would be higher than BNP levels.
      METHODS: Levels of pleural fluid NT-proBNP and BNP were measured by enzyme
      immunoassay in a total of 80 patients: 20 with congestive heart failure, 20
      status post-coronary artery bypass graft, 20 with carcinoma, and 20 with
      pneumonia. RESULTS: Comparison of NT-proBNP and BNP concentrations using the
      Spearman method of statistical analysis revealed a correlation coefficient of
      0.572, P < .001. Evaluation of the diagnostic accuracy of BNP and NT-proBNP in
      patients with pleural effusions of cardiac origin demonstrated an area under the
      receiver operating characteristic curve of 0.700 (95% CI, 0.569-0.831) and 0.835
      (95% CI, 0.721-0.949), respectively. CONCLUSIONS: Although levels of pleural
      fluid BNP have a statistically significant correlation with those of NT-proBNP,
      this relationship only explains 32% of the variance in NT-proBNP levels.
      Furthermore, when compared with BNP, NT-proBNP is a more accurate diagnostic aid
      in the evaluation of pleural effusions of cardiac origin.

PMID- 20139230
TI  - Androgen abuse in athletes: detection and consequences.
AB  - CONTEXT: Doping with anabolic androgenic steroids (AAS) both in sports
      (especially power sports) and among specific subsets of the population is
      rampant. With increasing availability of designer androgens, significant efforts
      are needed by antidoping authorities to develop sensitive methods to detect their
      use. EVIDENCE ACQUISITION: The PubMed and Google Scholar search engines were used
      to identify publications addressing various forms of doping, methods employed in
      their detection, and adverse effects associated with their use. EVIDENCE
      SYNTHESIS: The list of drugs prohibited by the World Anti-Doping Agency (WADA)
      has grown in the last decade. The newer entries into this list include
      gonadotropins, estrogen antagonists, aromatase inhibitors, androgen precursors,
      and selective androgen receptor modulators. The use of mass spectrometry has
      revolutionized the detection of various compounds; however, challenges remain in
      identifying newer designer androgens because their chemical signature is unknown.
      Development of high throughput bioassays may be an answer to this problem. It
      appears that the use of AAS continues to be associated with premature mortality
      (especially cardiovascular) in addition to suppressed spermatogenesis,
      gynecomastia, and virilization. CONCLUSION: The attention that androgen abuse has
      received lately should be used as an opportunity to educate both athletes and the
      general population regarding their adverse effects. The development of sensitive
      detection techniques may help discourage (at least to some extent) the abuse of
      these compounds. Investigations are needed to identify ways to hasten the
      recovery of the gonadal axis in AAS users and to determine the mechanism of
      cardiac damage by these compounds.

PMID- 20139231
TI  - Muscle fiber conduction slowing and decreased levels of circulating muscle
      proteins after short-term dexamethasone administration in healthy subjects.
AB  - CONTEXT: Glucocorticoids are known to decrease protein synthesis and impair
      membrane excitability of muscle fibers. However, their short-term effects on
      muscle structure and function of healthy subjects remain poorly understood.
      OBJECTIVE: Our objective was to investigate whether steroid administration could
      decrease the circulating levels of muscle proteins and modify myoelectric indexes
      of sarcolemmal excitability and fatigability. DESIGN: We conducted a single
      blind, placebo-controlled study in 20 men randomized to receive dexamethasone (8
      mg/d) or placebo for 1 wk. Blood sampling, force measurements for knee extensors
      and elbow flexors, and electrophysiological tests for biceps brachii, vastus
      lateralis and medialis, and tibialis anterior muscles were performed before and
      after the intervention. RESULTS: Dexamethasone administration improved force by
      6.0 +/- 6.0% (P = 0.01) for elbow flexors and by 8.5 +/- 5.5% (P < 0.01) for knee
      extensors, decreased levels of creatine kinase by 50.5 +/- 30.0% (P < 0.01) and
      myoglobin by 41.8 +/- 17.5% (P < 0.01), and impaired sarcolemmal excitability, as
      shown by the decline of muscle fiber conduction velocity for the four muscles
      (range from -6 to -10.5%, P < 0.05). Moreover, significant reductions of the
      myoelectric manifestations of fatigue were observed for the four muscles; the
      decrease in the rate of change of the mean frequency of the electromyographic
      power spectrum ranged from -22.6 to -43.9% (P < 0.05). In contrast, no
      significant changes were observed in muscle excitability and fatigability in
      subjects who received the placebo. CONCLUSIONS: The demonstration that
      glucocorticoid-induced muscle impairments can be unraveled by means of blood
      sampling and noninvasive electrophysiological tests has clinical implications for
      the early identification of subclinical or preclinical forms of myopathy in
      treated patients.

PMID- 20139232
TI  - Soluble CD36 (sCD36) clusters with markers of insulin resistance, and high sCD36
      is associated with increased type 2 diabetes risk.
AB  - CONTEXT AND OBJECTIVE: Soluble CD36 (sCD36) may be an early marker of insulin
      resistance and atherosclerosis. The objective of this prospective study was to
      evaluate sCD36 as a predictor of type 2 diabetes and to study its relationship
      with components of the metabolic syndrome (MetSy). DESIGN, SETTING, PARTICIPANTS,
      AND OUTCOME MEASURES: We conducted a case-referent study nested within a
      population-based health survey. Baseline variables included sCD36, body mass
      index, blood pressure, blood lipids, adipokines, inflammatory markers, and beta
      cell function. A total of 173 initially nondiabetic cohort members who developed
      type 2 diabetes during 10 yr of follow-up were matched (1:2) with referents.
      Exploratory factor analysis was applied to hypothesize affiliation of sCD36 to
      the MetSy components. RESULTS: Doubling of baseline sCD36 increases the odds
      ratio for diabetes development by 1.24 in the general study population and by
      1.45 in the female population (P < 0.025). Comparing upper sCD36 quartiles with
      lower, odds ratio for diabetes was 4.6 in women (P = 0.001), 3.15 in men (P =
      0.011), and 2.6 in obese individuals (P < 0.025). Multivariate analysis shows
      that sCD36 does not predict diabetes independent of fasting plasma glucose and
      insulin. Factor analysis of 15 variables generates a six-factor model explaining
      66-69% of total variance, where sCD36, body mass index, insulin, proinsulin, and
      leptin were assigned to the obesity/insulin resistance cluster. CONCLUSIONS:
      Upper quartile sCD36 is associated with elevated diabetes risk independent of
      age, gender, and obesity. Baseline sCD36 does not, however, predict diabetes
      independent of fasting glucose and insulin. sCD36 clusters with important markers
      of insulin resistance and MetSy that are key predictors of type 2 diabetes.

PMID- 20139233
TI  - Effects on lipoprotein particles of long-term dehydroepiandrosterone in elderly
      men and women and testosterone in elderly men.
AB  - CONTEXT: Although age-related declines in dehydroepiandrosterone sulfate (DHEAS)
      and testosterone are associated with cardiovascular risk, it remains to be
      determined whether replacement of these hormones improves cardiovascular risk
      factors. OBJECTIVE: This study sought to determine the effect of long-term
      replacement of dehydroepiandrosterone (DHEA) in elderly men and women and
      testosterone in elderly men on lipid and lipoprotein concentrations and particle
      sizes. METHODS: A 2-yr randomized, placebo-controlled, double-blind study was
      conducted in 87 elderly men with low levels of DHEAS and bioavailable
      testosterone and 57 elderly women with low levels of DHEAS. Among elderly men, 29
      received DHEA (75 mg/d), 27 received testosterone (5 mg/d), and 31 received
      placebo. Among the elderly women, 27 received DHEA (50 mg/d), and 30 received
      placebo. Baseline lipoprotein profiles in the elderly were compared to healthy
      younger participants. Low-density lipoprotein (LDL) and high-density lipoprotein
      (HDL) particle sizes and concentrations were quantified using nuclear magnetic
      resonance spectroscopy. RESULTS: The elderly had higher concentrations of total
      cholesterol, triglycerides, LDL cholesterol, total LDL particles, and small,
      dense LDL particles than the young. In men, neither DHEA nor testosterone
      affected LDL or HDL particle concentrations. In women, DHEA reduced HDL
      cholesterol [median difference (95% confidence intervals), -5.0 (-8.0, -2.0)
      mg/dl; P = 0.002] and the number of large HDL particles [-1.0 (-1.8, -0.2)
      micromol/liter; P = 0.003]. CONCLUSIONS: Long-term DHEA and testosterone had no
      significant effect on plasma lipoproteins in elderly men, but elderly women
      showed a lowering of the large HDL particles that may have potential adverse
      clinical implications.

PMID- 20139234
TI  - To stimulate or withdraw? A cost-utility analysis of recombinant human
      thyrotropin versus thyroxine withdrawal for radioiodine ablation in patients with
      low-risk differentiated thyroid cancer in the United States.
AB  - CONTEXT: Use of recombinant human TSH (rhTSH) prior to radioactive iodine remnant
      ablation for patients with differentiated thyroid cancer avoids the hypothyroid
      state and improves quality of life. European studies have shown that use of rhTSH
      vs. thyroid hormone withdrawal is a cost-effective method for preparing patients
      for ablation. OBJECTIVE: The objective of the study was to determine the cost
      utility of rhTSH prior to ablation in the United States. DESIGN/SETTING/SUBJECTS:
      A Markov decision model was developed for a hypothetical group of adult patients
      with low-risk differentiated thyroid cancer who were prepared for ablation by
      either rhTSH or thyroid hormone withdrawal. Patients entered the model after
      initial thyroidectomy; follow-up was in accordance with current American Thyroid
      Association guidelines. Input data were obtained from the literature, Medicare
      reimbursement schedule, and U.S. Bureau of Labor Statistics. Sensitivity analyses
      were performed for all clinically relevant inputs. MAIN OUTCOME MEASURES: Cost
      utility, measured in U.S. dollars per quality-adjusted life-year ($/QALY), was
      measured. RESULTS: Use of rhTSH yielded an incremental cost-utility of
      $52,554/QALY (95% confidence interval $52,058-53,050/QALY) (incremental societal
      cost of $1,365/patient; incremental benefit of 0.026 QALY/patient). The majority
      of cost and benefit occurs during the preablation, ablation, and postablation
      period; differences in cost are due to cost of rhTSH and differences in
      productivity loss (days off work). The model was most sensitive to changes in
      time off work, cost of rhTSH, and differences in utilities of health states.
      CONCLUSIONS: In the United States, the cost-effectiveness of rhTSH for ablation
      in patients with low-risk differentiated thyroid cancer is highly dependent on
      potential variations in cost of rhTSH, rates of remnant ablation, time off work,
      and quality of life.

PMID- 20139235
TI  - Maternal vitamin D status determines bone variables in the newborn.
AB  - CONTEXT: Vitamin D regulates 3% of the human genome, including effects on bone
      health throughout life. Maternal vitamin D status may program neonatal skeletal
      development. The objective here was to determine the association of mothers'
      vitamin D status with bone variables of their newborns. SUBJECTS AND METHODS: In
      a birth hospital, pregnant women (n = 125) participated in a cross-sectional
      study with a longitudinal follow-up of the pregnancy. The mean (sd) values for
      age, body mass index before pregnancy, pregnancy weight gain, and total vitamin D
      intake in mothers were 31 (4) yr, 23.5 (3.7) kg/m(2), 13.1 (4.3) kg, and 14.3
      (5.8) microg, respectively. All newborns were full-term, 99% were appropriate for
      gestational age, and 53% were boys. Blood samples were collected from mothers
      during the first trimester and 2 d postpartum and from umbilical cords at birth
      for analysis of serum 25-hydroxyvitamin D (S-25-OHD), PTH, and bone remodeling
      markers. Bone variables were measured by pQCT at the 20% site of the newborn
      tibia on an average of 10 (11) d postpartum. Bone contour was analyzed with a
      single threshold of 180 mg/mm(3) for the detection of total bone mineral density
      (BMD), bone mineral content (BMC), and cross-sectional area (CSA). RESULTS: Mean
      S-25-OHD was 41.0 (13.6), 45.1 (11.9), and 50.7 (14.9) nmol/liter during the
      first trimester, postpartum, and in the umbilical cord, respectively. The median
      value of the individual means for first trimester and the 2-d postpartum S-25-OHD
      was 42.6 nmol/liter, which was used as cutoff to define two equal-sized groups.
      Groups are called below median and above median in the text. Newborns below
      median were heavier (P = 0.05), and 60% were boys. Tibia bone mineral content was
      0.047 (95% confidence interval, 0.011-0.082) g/cm higher (P = 0.01), and cross
      sectional area was 12.3 (95% confidence interval, 2.0-22.6) mm(2) larger (P =
      0.02), but no difference in bone mineral density was observed, above median
      compared with below median group. These results were adjusted for newborn Z-score
      birth weight, maternal height, and newborn age at the measurement. A positive,
      significant correlation was observed between remodeling markers in mothers at
      different time points and above median group in the cord. CONCLUSIONS: Although
      the mean total intake of vitamin D among mothers met current Nordic
      recommendations, 71% of women and 15% of newborns were vitamin D deficient during
      the pregnancy. Our results suggest that maternal vitamin D status affects bone
      mineral accrual during the intrauterine period and influences bone size. More
      efforts should be made to revise current nutrition recommendations for pregnant
      women that may have permanent effects on the well-being of children.

PMID- 20139236
TI  - Disinfection by-products in drinking water and colorectal cancer: a meta
      analysis.
AB  - BACKGROUND: There is inconclusive evidence from observational studies that
      disinfection by-products (DBPs) in drinking water are associated with colorectal
      cancer. METHODS: A literature search, without language or time limits, was
      performed to identify relevant case-control and cohort studies. Separate risk
      estimates for colon and rectal cancer were extracted from studies meeting the
      inclusion criteria. Relative risks (RRs) or odds ratios (ORs) comparing the
      highest exposure category with the lowest were pooled using random effects
      methods. RESULTS: A total of 13 studies (3 cohort and 10 case-control) were
      analysed. For colon cancer, the pooled RR estimates were 1.11 [95% confidence
      interval (CI): 0.73-1.70] for cohort studies, 1.33 (95% CI: 1.12-1.57) for case
      control studies and 1.27 (95% CI: 1.08-1.50) combining both study types. For
      rectal cancer, the corresponding RR estimates were 0.88 (0.57-1.35), 1.40 (1.15
      1.70) and 1.30 (1.06-1.59). Sensitivity analysis showed these results were not
      importantly influenced by any single study. Publication bias was not evident for
      the colon cancer analysis but may have been a minor issue for the rectal cancer
      analysis. The results for rectal cancer may have been influenced by the quality
      of the studies. CONCLUSIONS: The study findings provide limited evidence of a
      positive association between colorectal cancer and exposure to DBPs in drinking
      water. The small number of studies and limitations in study quality prevent
      causal inference.

PMID- 20139237
TI  - Activated alleles of the Schizosaccharomyces pombe gpa2+ Galpha gene identify
      residues involved in GDP-GTP exchange.
AB  - The Schizosaccharomyces pombe glucose/cyclic AMP (cAMP) signaling pathway
      includes the Gpa2-Git5-Git11 heterotrimeric G protein, whose Gpa2 Galpha subunit
      directly binds to and activates adenylate cyclase in response to signaling from
      the Git3 G protein-coupled receptor. To study intrinsic and extrinsic regulation
      of Gpa2, we developed a plasmid-based screen to identify mutationally activated
      gpa2 alleles that bypass the loss of the Git5-Git11 Gbetagamma dimer to repress
      transcription of the glucose-regulated fbp1(+) gene. Fifteen independently
      isolated mutations alter 11 different Gpa2 residues, with all but one conferring
      a receptor-independent activated phenotype upon integration into the gpa2(+)
      chromosomal locus. Biochemical characterization of three activated Gpa2 proteins
      demonstrated an increased GDP-GTP exchange rate that would explain the mechanism
      of activation. Interestingly, the amino acid altered in the Gpa2(V90A) exchange
      rate mutant protein is in a region of Gpa2 with no obvious role in Galpha
      function, thus extending our understanding of Galpha protein structure-function
      relationships.

PMID- 20139238
TI  - F-actin dynamics in Neurospora crassa.
AB  - This study demonstrates the utility of Lifeact for the investigation of actin
      dynamics in Neurospora crassa and also represents the first report of
      simultaneous live-cell imaging of the actin and microtubule cytoskeletons in
      filamentous fungi. Lifeact is a 17-amino-acid peptide derived from the
      nonessential Saccharomyces cerevisiae actin-binding protein Abp140p. Fused to
      green fluorescent protein (GFP) or red fluorescent protein (TagRFP), Lifeact
      allowed live-cell imaging of actin patches, cables, and rings in N. crassa
      without interfering with cellular functions. Actin cables and patches localized
      to sites of active growth during the establishment and maintenance of cell
      polarity in germ tubes and conidial anastomosis tubes (CATs). Recurrent phases of
      formation and retrograde movement of complex arrays of actin cables were observed
      at growing tips of germ tubes and CATs. Two populations of actin patches
      exhibiting slow and fast movement were distinguished, and rapid (1.2 microm/s)
      saltatory transport of patches along cables was observed. Actin cables
      accumulated and subsequently condensed into actin rings associated with septum
      formation. F-actin organization was markedly different in the tip regions of
      mature hyphae and in germ tubes. Only mature hyphae displayed a subapical collar
      of actin patches and a concentration of F-actin within the core of the
      Spitzenkorper. Coexpression of Lifeact-TagRFP and beta-tubulin-GFP revealed
      distinct but interrelated localization patterns of F-actin and microtubules
      during the initiation and maintenance of tip growth.

PMID- 20139240
TI  - Ste12 and Ste12-like proteins, fungal transcription factors regulating
      development and pathogenicity.
AB  - Ste12 and Ste12-like proteins are transcription factors found exclusively in the
      fungal kingdom. In the yeast model Saccharomyces cerevisiae, where the first
      member was identified, Ste12p was shown to regulate mating and
      invasive/pseudohyphal growth. In recent literature, there have been several
      reports of Ste12-like factors in multiple fungal systems, yeasts or filamentous
      fungi, with saprophytic or parasitic life-styles. In all these models, Ste12 and
      Ste12-like factors are involved in the regulation of fungal development and
      pathogenicity. In this review, we discuss the features, the regulation, and the
      role of Ste12 and Ste12-like factors by highlighting the similarities and
      dissimilarities that occur within this group.

PMID- 20139239
TI  - Genetic engineering of algae for enhanced biofuel production.
AB  - There are currently intensive global research efforts aimed at increasing and
      modifying the accumulation of lipids, alcohols, hydrocarbons, polysaccharides,
      and other energy storage compounds in photosynthetic organisms, yeast, and
      bacteria through genetic engineering. Many improvements have been realized,
      including increased lipid and carbohydrate production, improved H(2) yields, and
      the diversion of central metabolic intermediates into fungible biofuels.
      Photosynthetic microorganisms are attracting considerable interest within these
      efforts due to their relatively high photosynthetic conversion efficiencies,
      diverse metabolic capabilities, superior growth rates, and ability to store or
      secrete energy-rich hydrocarbons. Relative to cyanobacteria, eukaryotic
      microalgae possess several unique metabolic attributes of relevance to biofuel
      production, including the accumulation of significant quantities of
      triacylglycerol; the synthesis of storage starch (amylopectin and amylose), which
      is similar to that found in higher plants; and the ability to efficiently couple
      photosynthetic electron transport to H(2) production. Although the application of
      genetic engineering to improve energy production phenotypes in eukaryotic
      microalgae is in its infancy, significant advances in the development of genetic
      manipulation tools have recently been achieved with microalgal model systems and
      are being used to manipulate central carbon metabolism in these organisms. It is
      likely that many of these advances can be extended to industrially relevant
      organisms. This review is focused on potential avenues of genetic engineering
      that may be undertaken in order to improve microalgae as a biofuel platform for
      the production of biohydrogen, starch-derived alcohols, diesel fuel surrogates,
      and/or alkanes.

PMID- 20139241
TI  - Cholecalciferol loading dose guideline for vitamin D-deficient adults.
AB  - INTRODUCTION: Severe vitamin D deficiency is very common. Evidence-based
      guidelines for rapid correction with high-dose oral cholecalciferol are not yet
      available. OBJECTIVE: To develop a practical cholecalciferol loading dose
      regimen. MATERIALS AND METHODS: A total of 208 vitamin D-deficient subjects
      (serum 25-hydroxyvitamin D(3) (25-OHD(3)) level <50 nmol/l), aged 18-88 years,
      were treated with solubilized cholecalciferol, 50,000 IU/ml. They received either
      25,000 IU every fortnight for 8 weeks (total dose 100,000 IU), 25,000 IU every
      week for 6 weeks (total dose 150,000 IU), or 25 000 IU every week for 8 weeks
      (total dose 200,000 IU). Blood samples were collected at baseline and 10 days
      after the final dose of cholecalciferol. Results Most patients were severely
      vitamin D deficient: 76% had a serum 25-OHD(3) level <30 nmol/l at baseline.
      Cholecalciferol in a cumulative dose of 100,000, 150,000, and 200,000 IU
      increased mean serum 25-OHD(3) level by 29 nmol/l (95% confidence interval (CI):
      23-35 nmol/l), 43 nmol/l (95% CI: 36-50 nmol/l), and 69 nmol/l (95% CI: 64-75
      nmol/l) respectively. The change in 25-OHD(3) (Delta25-OHD(3)) was related to the
      dose per kilogram body weight (R(2)=0.38, P<0.0001), and is described by the
      equation: Delta25-OHD(3)=0.025x(dose per kg body weight). CONCLUSION: The
      cholecalciferol loading dose required to reach the serum 25-OHD(3) target level
      of 75 nmol/l can be calculated as follows: dose (IU)=40x(75-serum 25-OHD(3))xbody
      weight.

PMID- 20139242
TI  - Odontogenic myxofibroma synchronous with primary angiosarcoma of the spleen.
AB  - Odontogenic myxofibroma of the temporomandibular joint (TMJ) is a rare tumour;
      moreover, primary splenic angiosarcoma (PAS) in paediatric patients is extremely
      rare. We report on a 15-year-old boy who presented with right TMJ swelling and
      subsequently developed epigastric and right upper quadrant pain. The TMJ swelling
      proved to be odontogenic myxofibroma and the abdominal pain was a result of
      primary splenic angiosarcoma with hepatic metastasis. We report for the first
      time the synchronous presentation of PAS and odontogenic myxofibroma in a
      paediatric patient, and we describe the radiological features along with the
      histological diagnosis and clinical outcome. Uptake in (18)F-2-fluoro-2-deoxy-D
      glucose positron emission tomography is also described for the first time for
      both these tumours.

PMID- 20139243
TI  - Cryptococcal choroid plexitis: rare imaging findings of central nervous system
      cryptococcal infection in an immunocompetent individual.
AB  - Central nervous system (CNS) cryptococcosis is a common opportunistic fungal
      infection in immunocompromised patients, and the imaging findings differ from
      those in immunocompetent patients. Here, we present the imaging findings in an
      immunocompetent woman of a rare case of central nervous system cryptococcal
      choroid plexitis with trapped temporal horns, enlarged enhancing bilateral
      choroid plexuses and multiple intraventricular choroid plexus cysts.

PMID- 20139244
TI  - Intracranial transthecal subarachnoid fat emboli and subarachnoid haemorrhage
      arising from a sacral fracture and dural tear.
AB  - We present the case of a 28-year-old man with an unusual aetiology of lipid-dense
      material in the subarachnoid space. CT of the head at presentation was normal.
      MRI of the spine revealed a defect in the dura at L5/S1, with avulsed left L5 and
      S1 nerve roots. Haematoma and marrow fat were observed in close relation to the
      dural tear adjacent to the sacral fracture. Head CT and MRI subsequently
      demonstrated new lipid-dense material and haemorrhage in the subarachnoid space
      after sacral instrumentation, presumably owing to transthecal displacement of
      fatty marrow.

PMID- 20139245
TI  - Transjugular intrahepatic portocaval shunt placed through the strut of an
      inferior vena cava stent in a patient with Budd-Chiari syndrome: a technical
      modification.
AB  - Transjugular intrahepatic portocaval shunt (TIPS) is performed in patients with
      symptomatic Budd-Chiari syndrome (BCS) who do not have repairable hepatic veins.
      We report the case of a patient who had an inferior vena cava (IVC) stent placed
      previously as part of the management for BCS, and who subsequently required TIPS.
      The TIPS tract was created through the strut of the previously placed IVC stent;
      the TIPS stent was placed after dilatation of the liver parenchyma as well as the
      strut of the IVC stent. This novel technique of "strutplasty" of a previously
      placed stent as part of TIPS has not been reported in the literature.

PMID- 20139246
TI  - Misplaced pulmonary arteries in an adult patient with pulmonary hypertension.
AB  - Misalignment of pulmonary vessels, with or without alveolar capillary dysplasia,
      is a rare cause of persistent pulmonary hypertension in the newborn. The
      prognosis is poor, with virtually all patients succumbing to unremitting
      hypoxaemic respiratory failure and death during the newborn period. We report the
      CT and histological findings of misplaced pulmonary arteries in a previously
      healthy young adult patient who presented with pulmonary arterial hypertension.
      Contiguous high-resolution spiral CT angiography showed small pulmonary arteries
      coursing within the interlobular septa and enlarged central pulmonary arteries.
      Surgical lung biopsy demonstrated anomalous muscularised pulmonary arteries in
      the interlobular septa. This is, to our knowledge, the first report of misplaced
      pulmonary arteries presenting in an adult patient and may represent a forme
      fruste of the neonatal vascular anomaly. A possible association with pulmonary
      arterial hypertension is also suggested in this case.

PMID- 20139247
TI  - An unusual breast lesion: the ultrasonographic, mammographic, MRI and nuclear
      medicine findings of mammary hibernoma.
AB  - We report the case of a 42-year-old woman being treated for an ovarian cancer who
      was diagnosed at the age of 40. A CT-positron emission tomography (PET) scan
      performed as follow-up documented abnormal uptake in the right breast. Mammograms
      were negative for malignancy, while a focal hyperechoic lesion was observed on
      ultrasonography in the same breast. Thus, she was referred to our institution for
      breast MRI, which showed a focal area of enhancement with atypical features.
      Percutaneous biopsy was performed, and a mammary hibernoma was diagnosed.
      Radiological and pathological correlation was provided. To our knowledge, this is
      the only report that describes the features of this rare tumour on four different
      imaging modalities (mammography, ultrasonography, MRI and CT-PET).

PMID- 20139248
TI  - Benchmarking in radiology: apples and oranges?

PMID- 20139249
TI  - The radiation protection and therapy effects of mesenchymal stem cells in mice
      with acute radiation injury.
AB  - The aim of this study was to investigate the effects and mechanisms of
      mesenchymal stem cells (MSCs) on haematopoietic reconstitution in reducing bone
      marrow cell apoptosis effects in irradiated mice, and to research the safe and
      effective dosage of MSCs in mice with total body irradiation (TBI). After BALB/c
      mice were irradiated with 5.5 Gy cobalt-60 gamma-rays, the following were
      observed: peripheral blood cell count, apoptosis rate, cell cycle, colony-forming
      unit-granulocyte macrophage (CFU-GM) and colony-forming unit-fibroblast (CFU-F)
      counts of bone marrow cells and pathological changes in the medulla. The survival
      of mice infused with three doses of MSCs after 8.0 Gy or 10 Gy TBI was examined.
      The blood cells recovered rapidly in the MSC groups. The apoptotic ratio of bone
      marrow cells in the control group was higher at 24 h after radiation. A lower
      ratio of G0/G1 cell cycle phases and a higher ratio of G2/M and S phases, as well
      as a greater number of haematopoietic islands and megalokaryocytes in the bone
      marrow, were observed in the MSC-treated groups. MSCs induced recovery of CFU-GM
      and CFU-GM and improved the survival of mice after 8 Gy TBI, but 1.5 x 10(8) kg(
      1) of MSCs increased mortality. These results indicate that MSCs protected and
      treated irradiated mice by inducing haematopoiesis and reducing apoptosis. MSCs
      may be a succedaneous or intensive method of haematopoietic stem cell
      transplantation under certain radiation dosages, and could provide a valuable
      strategy for acute radiation syndrome.

PMID- 20139250
TI  - Increased renal uptake of technetium-99m HEDP in a patient with breast cancer.

PMID- 20139251
TI  - High-resolution CT findings in a patient with influenza A (H1N1) virus-associated
      pneumonia.

PMID- 20139253
TI  - Case report. Fractionated Helical Tomotherapy as an alternative to radiosurgery
      in patients unwilling to undergo additional radiosurgery for recurrent brain
      metastases.
AB  - Our clinic routinely treats brain metastases with stereotactic radiosurgery using
      a 6 megavoltage (MV) linear accelerator, cones, and a surgically attached head
      frame. Four patients declined repeat radiosurgery for new lesions due to their
      previous discomfort and a fifth patient could not complete radiosurgery because
      of uncontrolled nausea. Instead patients were treated with Helical Tomotherapy
      (HT). This report discusses the spatial dose distribution of HT as measured in a
      head phantom and the clinical course of these five patients. The planning target
      volume (PTV) was a 3 mm geometric expansion of the gross tumour volume (GTV). The
      prescribed dose to the PTV was 27 Gy in five daily fractions with the
      distribution optimised to deliver 30 Gy to the GTV. Patients were immobilised
      with a mask and the lesions were targeted by MV computerised tomography, an
      inherent feature of the system. One patient died six weeks later from systemic
      disease; the remaining patients survived eight to 16 months. No patient
      experienced an exacerbation of neurological symptoms following Helical
      Tomotherapy. These results suggest that fractionated Helical Tomotherapy for
      brain metastases may be a viable alternative to radiosurgery in patients unable
      or unwilling to undergo that procedure.

PMID- 20139254
TI  - MR spectroscopy and MR perfusion character of cerebral sparganosis: a case
      report.
AB  - The authors report the case of a 46-year-old woman with cerebral sparganosis
      resulting from infection with a larva of Spirometra. Computed tomography and
      magnetic resonance imaging revealed a mass lesion with prominent perifocal oedema
      in the left parietal lobe. Advanced imaging pulse sequences, including MR
      spectroscopy and MR perfusion, were performed. During surgery for the removal of
      a granuloma, the parasite was discovered and excised. Following treatment, the
      patient's neurological deficits markedly improved.

PMID- 20139255
TI  - Case report. Atlantoaxial synovial cyst causing isolated unilateral hypoglossal
      nerve paralysis.
AB  - Cervical synovial cysts are rare entities that are, most of the time,
      asymptomatic. They can cause nerve root or spinal cord compression, especially
      when acute haemorrhage or a marked increase in size occurs. Isolated unilateral
      hypoglossal nerve paralysis caused by compression of its cisternal segment is
      also an extremely rare condition. We report the case of a 51-year-old woman who
      presented with dysarthria and tongue fasciculation. MRI revealed an atlantoaxial
      synovial cyst that extended cranially through the hypoglossal canal and
      compressed the fibres of the left XII nerve on its cisternal segment. To our
      knowledge, this is the first case report of XII nerve paralysis being caused by
      an atlantoaxial synovial cyst.

PMID- 20139256
TI  - Case report. PET/CT appearance of desmoid tumour of the chest wall.
AB  - Desmoid tumours are rare, poorly circumscribed tumours that have a firm
      consistency and, although benign, have a remarkable tendency to infiltrate into
      surrounding structures. Extra-abdominal desmoid tumours involve mainly the
      extremities or the chest wall and are usually managed by wide radical resection.
      Moreover, desmoid tumours involving the chest wall are locally aggressive tumours
      with a high recurrence rate. We report a case of a pathologically proven desmoid
      tumour of the chest wall in a patient with a history of bilateral breast cancer
      and oesophageal cancer. We discuss the imaging appearances of this tumour on
      positron emission tomography combined with computed tomography (PET/CT) and
      magnetic resonance imaging.

PMID- 20139257
TI  - Case report. Primary hypothalamic third ventriclular Burkitt's lymphoma: a case
      report with emphasis on differential diagnosis.
AB  - A patient with primary Burkitt-type lymphoma of the central nervous system is
      presented. A hypothalamic-third ventricular tumour in a man 71 years of age was
      diagnosed histologically as Burkitt's lymphoma. Primary Burkitt's lymphoma of the
      hypothalamic region is extremely rare and has not been previously reported in
      adults.

PMID- 20139258
TI  - The impact factor game: the rising impact factor of the British Journal of
      Radiology--a success story?

PMID- 20139259
TI  - Evaluating novel radiation techniques for the treatment of cerebral metastases.

PMID- 20139260
TI  - Primary care access to diagnostics: a paradigm shift.
AB  - There is increasing medico-political impetus for the provision of direct access
      imaging services to primary care. This is likely to have fundamental effects on
      the way that imaging services are organised and provided, and radiologists need
      to be aware of the paradigm shift that is being promoted. This commentary
      summarises some of the key issues arising, and has been written to complement a
      recent conference organised by the British Institute of Radiology.

PMID- 20139261
TI  - Imaging acute pancreatitis.
AB  - Acute pancreatitis is a common condition (thought to be increasing in incidence
      worldwide), which has a highly variable clinical course. The radiologist plays a
      key role in the management of such patients, from diagnosis and staging to
      identification and treatment of complications, as well as in determining the
      underlying aetiology. The aim of this article is (i) to familiarize the reader
      with the pathophysiology of acute pancreatitis, the appearances of the various
      stages of pancreatitis, the evidence for the use of staging classifications and
      the associated complications and (ii) to review current thoughts on optimising
      therapy.

PMID- 20139262
TI  - Long-term melatonin administration attenuates low-LET gamma-radiation-induced
      lymphatic tissue injury during the reproductively active and inactive phases of
      Indian palm squirrels (Funambulus pennanti).
AB  - A comparative analysis of low linear energy transfer (LET) gamma-radiation
      induced damage in the lymphatic tissue of a tropical seasonal breeder, Indian
      palm squirrel (Funambulus pennanti), during its reproductively active phase (RAP)
      and inactive phase (RIP) was performed with simultaneous investigation of the
      effects of long-term melatonin pre-treatment (100 microg/100 g body weight). A
      total of 120 squirrels (60 during RAP and 60 during RIP) were divided into 12
      groups and sacrificed at 4, 24, 48, 72 and 168 h following 5 Gy gamma-radiation
      exposure; control groups were excluded from exposure. Total leukocyte count and
      absolute lymphocyte count (ALC) and melatonin only of peripheral blood,
      stimulation index, thiobarbituric-acid-reactive substances (TBARS) level,
      superoxide dismutase (SOD) activity, and the apoptotic index of spleen as
      analysed by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine
      triphosphate (dUTP) nick-end labelling (TUNEL) noted at observed time-points were
      significantly reduced in melatonin pre-treated groups during RAP and RIP. Long
      term melatonin pre-treatment mitigated radiation-induced alterations more
      prominently during RIP, as assessed by ALC, TBARS, SOD, TUNEL and caspase-3
      activity, at some time-points. Our results demonstrate an inhibitory role of
      melatonin on caspase-3 activity in splenocytes during RAP and RIP following gamma
      radiation-induced caspase-mediated apoptosis. Hence, we propose that melatonin
      might preserve the viability of immune cells of a seasonal breeder against
      background radiation, which is constantly present in the environment.

PMID- 20139263
TI  - Radiation dose and cancer risk in retrospectively and prospectively ECG-gated
      coronary angiography using 64-slice multidetector CT.
AB  - This study aimed to estimate the radiation dose and cancer risk to adults in
      England, the USA and Hong Kong associated with retrospectively and prospectively
      electrocardiogram (ECG)-gated coronary computed tomography angiography (CTA)
      using currently practised protocols in Hong Kong. The doses were simulated using
      the ImPACT spreadsheet. For retrospectively ECG-gated CTA with pitches of 0.2,
      0.22 and 0.24, the effective doses were 27.7, 23.6 and 20.7 mSv, respectively,
      for males and 23.6, 20.0 and 18.8 mSv, respectively, for females. For
      prospectively ECG-gated CTA, the effective dose was 3.7 mSv for both males and
      females. A table of lifetime attributable risks (LAR) of cancer incidence was set
      up for the English population for the purpose of estimating cancer risk induced
      by low-dose radiation exposure, as previously reported for US and Hong Kong
      populations. From the tables, the LAR of cancer incidence for a representative 50
      year-old subject was calculated for retrospectively ECG-gated CTA to be 0.112%
      and 0.227% for English males and females, respectively, 0.103% and 0.228% for US
      males and females, respectively, and was comparatively higher at 0.137% and
      0.370% for Hong Kong males and females, respectively; for prospectively ECG-gated
      CTA, the corresponding values were calculated to be 0.014% and 0.035% for English
      males and females, respectively, and 0.013% and 0.036% for US males and females,
      respectively, and again were higher at 0.017% and 0.060% for Hong Kong males and
      females, respectively. Our study shows that prospectively ECG-gated CTA reduces
      radiation dose and cancer risks by up to 87% compared with retrospectively ECG
      gated CTA.

PMID- 20139264
TI  - Vascular supply with angio-CT for superselective intra-arterial chemotherapy in
      advanced maxillary sinus cancer.
AB  - Recently popularised, the combined angiography and CT (angio-CT) system is useful
      for correctly identifying the feeding arteries and their perfusion in various
      organs. We applied this system for advanced maxillary cancer to expose its
      feeding arteries and their supplying territories. In addition to the maxillary
      artery, extramaxillary feeding arteries were usually observed, including the
      ophthalmic, accessory meningeal, facial, transverse facial and ascending palatine
      arteries. These extramaxillary feeding arteries exhibited uniform tendencies,
      depending on the site of extramaxillary tumour extension.

PMID- 20139265
TI  - High-resolution computed tomography findings in an HIV-positive patient with
      swine-origin influenza A (H1N1) virus-associated pneumonia.

PMID- 20139266
TI  - Case of the month. Ultrasound and MRI features of connatal cysts:
      clinicoradiological differentiation from other supratentorial periventricular
      cystic lesions.

PMID- 20139267
TI  - Does a flat panel detector reduce the patient radiation dose in interventional
      cardiology?
AB  - An internal audit has been performed to evaluate the patient radiation dose in
      the clinical use of X-ray cardiac flat panel detector (FPD) systems. Fluoroscopy
      and image acquisition (cine mode) programs are optimised for low-dose settings.
      The diagnostic and therapeutic interventional cardiac procedures are performed at
      6 pulse s(-1) for fluoroscopy and 15 frames s(-1) for image acquisition. The FPD
      entrance dose is configured for 29 nGy pulse(-1) in the fluoroscopy mode and 0.10
      microGy frame(-1) in the cine mode. From the data collected, the following local
      reference levels for coronary angiography and angioplasty have been obtained:
      kerma-area products 23 and 44 Gy cm(2), cumulative doses 376 and 776 mGy,
      fluoroscopy times 5 and 15.5 min and cine images 617 and 1163 images.

PMID- 20139268
TI  - Clinical relevance of the ROC and free-response paradigms for comparing imaging
      system efficacies.
AB  - Observer performance studies are widely used to assess medical imaging systems.
      Unlike technical/engineering measurements observer performance include the entire
      imaging chain and the radiologist. However, the widely used receiver operating
      characteristic (ROC) method ignores lesion localisation information. The free
      response ROC (FROC) method uses the location information to appropriately reward
      or penalise correct or incorrect localisations, respectively. This paper
      describes a method for improving the clinical relevance of FROC studies. The
      method consists of assigning appropriate risk values to the different lesions
      that may be present on a single image. A high-risk lesion is one that is critical
      to detect and act upon, and is assigned a higher risk value than a low-risk
      lesion, one that is relatively innocuous. Instead of simply counting the number
      of lesions that are detected, as is done in conventional FROC analysis, a risk
      weighted count is used. This has the advantage of rewarding detections of high
      risk lesions commensurately more than detections of lower risk lesions.
      Simulations were used to demonstrate that the new method, termed case-based
      analysis, results in a higher figure of merit for an expert who detects more high
      risk lesions than a naive observer who detects more low-risk lesions, even though
      both detect the same total number of lesions. Conventional free-response analysis
      is unable to distinguish between the two types of observers. This paper also
      comments on the issue of clinical relevance of ROC analysis vs. FROC for tasks
      that involve lesion localisation.

PMID- 20139269
TI  - Patient peak skin doses from cardiac interventional procedures.
AB  - Interventional cardiac procedures not only lead to significant effective doses
      for the patient but also can potentially cause deterministic effects on the
      patient's skin. Information about the peak (maximal) skin doses (PSD) received by
      patients during percutaneous transluminal coronary angioplasty procedures were
      collected from three cardiac catheter rooms. Cumulative dose at the
      interventional reference point (CD(IRP)) was collected for 161 patients and for
      16 patients PSD was determined using Gafchromic dosimetry films. The comparison
      showed that CD(IRP) readings give a useful but conservative estimation of patient
      peak skin dose as it can lead to a significant overestimation. The median and
      third quartile values of CD(IRP) were 0.64 and 0.92 Gy, respectively. The 2 Gy
      threshold for deterministic effects was exceeded in nine patients. A good
      correlation was found between CD(IRP) and kerma area product measurements while
      the correlation with fluorography time was very weak.

PMID- 20139270
TI  - Trends for the past 10 years and international comparisons of the structure of
      Korean radiation oncology.
AB  - OBJECTIVE: Study aims include determination of nationwide structural
      characteristics of radiation oncology facilities, types of radiation therapy
      equipment, availability of human resources and trends and comparisons with
      previous surveys. METHODS: An annual nationwide survey was conducted to collect
      the statistics of infrastructure since 1997. All requested questionnaires have
      been identical for 10 years. The questionnaires included status on basic
      radiation therapy facilities, human resources and radiation therapy equipment.
      Journal and statistical data reviews were performed to evaluate the structure of
      other countries. RESULTS: Radiation oncology facilities have steadily increased
      for 10 years and reached 60 sites in 2006. Also a steady increase of 1.5 times
      for linear accelerators, 5.8 times for computed tomography simulators and 3.0
      times for radiation treatment planning systems was noted. Meanwhile, cobalt-60
      teletherapy units and hyperthermia equipment had steadily deceased for 10 years.
      The number of human resources has steadily increased for the past 10 years,
      especially for radiation therapy technologists. However, radiation therapy
      equipment and human resources per population are relatively low compared with
      advanced countries. CONCLUSIONS: This study will assist preparation of the
      administrative planning policy of radiation oncology and should be useful to
      indicate the direction of future development and educational training programs in
      Korea and possibly in other countries.

PMID- 20139271
TI  - Anti-programmed cell death 1 antibody reduces CD4+PD-1+ T cells and relieves the
      lupus-like nephritis of NZB/W F1 mice.
AB  - Programmed cell death 1 (PD-1) is an immunosuppressive receptor that transduces
      an inhibitory signal into activated T cells. Although a single nucleotide
      polymorphism in the gene for PD-1 is associated with susceptibility to systemic
      lupus erythematosus, the role of PD-1 in systemic lupus erythematosus is still
      not well understood. In this study, we used NZB/W F1 mice, a model of lupus-like
      nephritis, to examine the function of PD-1 and its ligands. PD-1 was
      predominantly expressed on CD4(+) T cells that infiltrated the kidney, and
      CD4(+)PD-1(high) T cells produced higher levels of IFN-gamma than CD4(+)PD-1(low)
      or CD4(+)PD-1(-) T cells. Stimulation with PMA/ionomycin caused splenic CD4(+)PD
      1(+) T cells to secrete high levels of IFN-gamma, IL-10, low levels of TNF-alpha,
      faint levels of IL-2, IL-21, and no IL-4, IL-17. In vivo anti-PD-1 mAb treatment
      reduced the number of CD4(+)PD-1(+) T cells in the kidney of NZB/W F1 mice and
      significantly reduced their mortality rate (p = 0.03). Conversely, blocking PD-L1
      using an anti-PD-L1 mAb increased the number of CD4(+)PD-1(+) T cells in the
      kidney, enhanced serum IFN-gamma, IL-10, and IgG2a ds-DNA-Ab levels, accelerated
      the nephritis, and increased the mortality rate. We conclude that CD4(+)PD
      1(high) T cells are dysregulated IFN-gamma-producing, proinflammatory cells in
      NZB/W F1 mice.

PMID- 20139272
TI  - Therapeutic glucocorticoid-induced TNF receptor-mediated amplification of CD4+ T
      cell responses enhances antiparasitic immunity.
AB  - Chronic infectious diseases and cancers are often associated with suboptimal
      effector T cell responses. Enhancement of T cell costimulatory signals has been
      extensively studied for cancer immunotherapy but not so for the treatment of
      infectious disease. The few previous attempts at this strategy using infection
      models have lacked cellular specificity, with major immunoregulatory mechanisms
      or innate immune cells also being targeted. In this study, we examined the
      potential of promoting T cell responses via the glucocorticoid-induced TNF
      receptor (GITR) family-related protein in a murine model of visceral
      leishmaniasis. GITR stimulation during established infection markedly improved
      antiparasitic immunity. This required CD4(+) T cells, TNF, and IFN-gamma, but
      crucially, was independent of regulatory T (Treg) cells. GITR stimulation
      enhanced CD4(+) T cell expansion without modulating Treg cell function or
      protecting conventional CD4(+) T cells from Treg cell suppression. GITR
      stimulation substantially improved the efficacy of a first-line visceral
      leishmaniasis drug against both acute hepatic infection and chronic infection in
      the spleen, demonstrating its potential to improve clinical outcomes. This study
      identifies a novel strategy to therapeutically enhance CD4(+) T cell-mediated
      antiparasitic immunity and, importantly, achieves this goal without impairment of
      Treg cell function.

PMID- 20139273
TI  - IL-17 activates the canonical NF-kappaB signaling pathway in autoimmune B cells
      of BXD2 mice to upregulate the expression of regulators of G-protein signaling
      16.
AB  - We previously identified that autoreactive B cells from BXD2 mice can be targeted
      by IL-17, leading to upregulation of the expression of regulators of G-protein
      signaling (Rgs) genes that facilitated the development of spontaneous germinal
      centers. Little is known about the signaling pathway used by IL-17 to upregulate
      RGS. In the current study, we found that IL-17 rapidly activates the canonical NF
      kappaB signaling pathway and that BXD2 B cells exhibit higher basal and activated
      phosphorylated p65 levels than B6 or BXD2-Il17ra(-/-) B cells. Inhibition of p65
      phosphorylation downregulated RGS16 expression and abrogated the IL-17-induced
      chemotactic arrest of B cells in response to CXCL12. Knockdown of TNFR-associated
      factor 6 or NF-kappaB activator 1 in 70Z/3 pre-B cells led to decreased Rgs16
      expression, indicating that both of these two genes are involved in IL-17
      mediated activation of NF-kappaB signaling in B cells. These findings identify
      the signaling pathway regulated by IL-17 to contribute to the development of
      spontaneous germinal centers in autoimmune BXD2 mice.

PMID- 20139274
TI  - IL-33 exacerbates autoantibody-induced arthritis.
AB  - Rheumatoid arthritis pathogenesis comprises dysregulation in both innate and
      adaptive immunity. There is therefore intense interest in the factors that
      integrate these immunologic pathways in rheumatoid arthritis. In this paper, we
      report that IL-33, a novel member of the IL-1 family, can exacerbate anti-glucose
      6-phosphate isomerase autoantibody-induced arthritis (AIA). Mice lacking ST2
      (ST2(-/-)), the IL-33 receptor alpha-chain, developed attenuated AIA and reduced
      expression of articular proinflammatory cytokines. Conversely, treatment of wild
      type mice with rIL-33 significantly exacerbated AIA and markedly enhanced
      proinflammatory cytokine production. However, IL-33 failed to increase the
      severity of the disease in mast cell-deficient or ST2(-/-) mice. Furthermore,
      mast cells from wild-type, but not ST2(-/-), mice restored the ability of ST2(-/
      ) recipients to mount an IL-33-mediated exacerbation of AIA. IL-33 also enhanced
      autoantibody-mediated mast cell degranulation in vitro and in synovial tissue in
      vivo. Together these results demonstrate that IL-33 can enhance autoantibody
      mediated articular inflammation via promoting mast cell degranulation and
      proinflammatory cytokine production. Because IL-33 is derived predominantly from
      synovial fibroblasts, this finding provides a novel mechanism whereby a host
      tissue-derived cytokine can regulate effector adaptive immune response via
      enhancing innate cellular activation in inflammatory arthritis.

PMID- 20139275
TI  - IL-12 and IL-27 sequential gene therapy via intramuscular electroporation
      delivery for eliminating distal aggressive tumors.
AB  - Eradication of residual malignancies and metastatic tumors via a systemic
      approach is the key for successfully treating cancer and increasing cancer
      patient survival. Systemic administration of IL-12 protein in an acute large dose
      is effective but toxic. Systemic administration of IL-12 gene by persistently
      expressing a low level of IL-12 protein may reduce the systemic toxicity but only
      eradicates IL-12-sensitive tumors. In this study, we discovered that sequential
      administration of IL-12- and IL-27-encoding DNA, referred to as sequential IL-12-
      >IL-27 (IL-12 administration followed by IL-27 administration 10 d after) gene
      therapy, not only eradicated IL-12-sensitive CT26 tumors from 100% of mice but
      also eradicated the highly malignant 4T1 tumors from 33% of treated mice in
      multiple independent experiments. This IL-12-->IL-27 sequential gene therapy is
      not only superior to IL-12-encoding plasmid DNA given a total of two times at a
      10-d interval sequential gene therapy for eliminating tumors but also for
      inducing CTL activity, increasing T cell infiltration into tumors, and yielding a
      large number of tumor-specific IFN-gamma-positive CD8 T cells. Notably, depletion
      of either T or NK cells during the IL-27 treatment phase reverses tumor
      eradication, suggesting an NK cell requirement for this sequential gene therapy
      mediated tumor eradication. Both reversal of the administration sequence and
      coadministration of IL-12 and IL-27 impaired tumor eradication in 4T1 tumor
      bearing mice. This IL-12-->IL-27 sequential gene therapy, via sequential
      administration of IL-12- and IL-27-encoding plasmid DNA into tumor-bearing mice
      through i.m. electroporation, provides a simple but effective approach for
      eliminating inaccessible residual tumors.

PMID- 20139276
TI  - Complement component C3 binds to activated normal platelets without preceding
      proteolytic activation and promotes binding to complement receptor 1.
AB  - It has been reported that complement is activated on the surface of activated
      platelets, despite the presence of multiple regulators of complement activation.
      To reinvestigate the mechanisms by which activated platelets bind to complement
      components, the presence of complement proteins on the surfaces of nonactivated
      and thrombin receptor-activating peptide-activated platelets was analyzed by flow
      cytometry and Western blot analyses. C1q, C4, C3, and C9 were found to bind to
      thrombin receptor-activating peptide-activated platelets in lepirudin
      anticoagulated platelet-rich plasma (PRP) and whole blood. However, inhibiting
      complement activation at the C1q or C3 level did not block the binding of C3 to
      activated platelets. Diluting PRP and chelating divalent cations also had no
      effect, further indicating that the deposition of complement components was
      independent of complement activation. Furthermore, washed, activated platelets
      bound added C1q and C3 to the same extent as platelets in PRP. The use of mAbs
      against different forms of C3 demonstrated that the bound C3 consisted of
      C3(H(2)O). Furthermore, exogenously added soluble complement receptor 1 was shown
      to bind to this form of platelet-bound C3. These observations indicate that there
      is no complement activation on the surface of platelets under physiological
      conditions. This situation is in direct contrast to a number of pathological
      conditions in which regulators of complement activation are lacking and
      thrombocytopenia and thrombotic disease are the ultimate result. However, the
      generation of C3(H(2)O) represents nonproteolytic activation of C3 and after
      factor I cleavage may act as a ligand for receptor binding.

PMID- 20139277
TI  - NK cell patrolling and elimination of donor-derived dendritic cells favor
      indirect alloreactivity.
AB  - Direct presentation of foreign MHC molecules expressed by donor-derived dendritic
      cells (DCs) has generally been considered the dominant pathway of allorecognition
      in acute transplant rejection. However, recent studies implicate preferential
      activation of the indirect pathway by host DCs. The respective importance of each
      pathway and the mechanisms that determine their relative contributions remain to
      be clearly established. In this study, using two-photon microscopy, we visualized
      host NK cell interactions with syngeneic and allogeneic DCs within intact lymph
      nodes of mice. Upon contact with allogeneic DCs, NK cells formed prolonged
      interactions that led directly to target cell lysis. This rapid elimination
      limited the ability of allogeneic DCs to stimulate primary and recall T cell
      responses. To discriminate whether donor or host DCs are principally involved in
      presenting Ag derived from allografts, we used CD11c-diphtheria toxoid receptor
      mice to conditionally ablate CD11c(+) DCs and to show that direct presentation by
      donor DCs is alone insufficient to elicit acute allograft rejection. We thus
      propose that rapid elimination of allogeneic DCs limits direct Ag presentation
      and thereby favors the indirect pathway of alloreactivity.

PMID- 20139278
TI  - Public TCR use by herpes simplex virus-2-specific human CD8 CTLs.
AB  - Recombination of germline TCR alpha and beta genes generates polypeptide
      receptors for MHC peptide. Ag exposure during long-term herpes simplex infections
      may shape the T cell repertoire over time. We investigated the CD8 T cell
      response to HSV-2 in chronically infected individuals by sequencing the
      hypervariable regions encoding TCR alpha and beta polypeptides from T cell clones
      recognizing virion protein 22 aa 49-57, an immunodominant epitope. The most
      commonly detected TCRBV gene segment, found in four of five subjects and in 12 of
      50 independently derived T cell clones, was TCRBV12-4. Nineteen to seventy-two
      percent of tetramer-binding cells in PBMCs were stained ex vivo with a TCRBV12
      mAb. Three alpha-chain and three beta-chain public TCR sequences were shared
      between individuals. Public heterodimers were also detected. Promiscuous pairing
      of a specific TCRVA1-1 sequence with several different TCRB polypeptides was
      observed, implying a dominant structural role for the TCRA chain for these
      clonotypes. Functional avidity for cytotoxicity and IFN-gamma release was
      relatively invariant, except for one subject with both high avidity and unique
      TCR sequences and lower HSV-2 shedding. These data indicate that the CD8 response
      to a dominant alpha-herpesvirus epitope converges on preferred TCR sequences with
      relatively constant functional avidity.

PMID- 20139279
TI  - Five HLA-DP molecules frequently expressed in the worldwide human population
      share a common HLA supertypic binding specificity.
AB  - Compared with DR and DQ, knowledge of the binding repertoires and specificities
      of HLA-DP alleles is somewhat limited. However, a growing body of literature has
      indicated the importance of DP-restricted responses in the context of cancer,
      allergy, and infectious disease. In the current study, we developed high
      throughput binding assays for the five most common HLA-DPB1 alleles in the
      general worldwide population. Using these assays on a comprehensive panel of
      single-substitution analogs and large peptide libraries, we derived novel
      detailed binding motifs for DPB1*0101 and DPB1*0501. We also derived more
      detailed quantitative motifs for DPB1*0201, DPB1*0401, and DPB1*0402, which were
      previously characterized on the basis of sets of eluted ligands and/or limited
      sets of substituted peptides. Unexpectedly, all five DP molecules, originally
      selected only on the basis of their frequency in human populations, were found to
      share largely overlapping peptide motifs. Testing panels of known DP epitopes and
      a panel of peptides spanning a set of Phleum pratense Ags revealed that these
      molecules also share largely overlapping peptide-binding repertoires. This
      demonstrates that a previously hypothesized DP supertype extends far beyond what
      was originally envisioned and includes at least three additional very common DP
      specificities. Taken together, these DP supertype molecules are found in >90% of
      the human population. Thus, these findings have important implications for
      epitope-identification studies and monitoring of human class II-restricted immune
      responses.

PMID- 20139280
TI  - Stimulation of naive CD8+ T cells by a variant viral epitope induces activation
      and enhanced apoptosis.
AB  - Classically, naive T cells recognize a specific peptide-MHC complex resulting in
      their activation and differentiation. However, it is known that T cells also have
      the ability to interact productively with variant ligands, indicating a
      flexibility in TCR Ag recognition. These altered peptide ligands have been shown
      to trigger responses ranging from complete activation to full inhibition of T
      cell responses, and thus may play an important role in initiating or sustaining T
      cell-mediated immunity. We have found that influenza virus-specific CD8(+) TCR
      transgenic T cells differentially respond to a native (agonist) and variant viral
      epitope, differing in two amino acids that are thought to alter TCR recognition.
      In response to stimulation with the agonist epitope, these cells activate,
      proliferate, and differentiate into effector CTLs. Conversely, stimulation with
      the variant epitope results in activation, proliferation, and development of
      effector activity followed by rapid and extensive apoptotic cell death.
      Stimulation of the T cells with the altered ligand results in an inability to
      sustain the expression of the prosurvival molecules, Bcl-2 and Bcl-xL. These data
      suggest that the response to the agonist and variant epitopes may reflect TCR
      avidity-dependent differential signaling through the TCR, resulting either in
      activation-dependent T cell proliferative expansion and survival or in the
      accelerated death of acutely activated differentiating T cells. This process of
      CD8(+) T cell activation, proliferation, and differentiation followed by rapid
      cell death may represent a novel mechanism of altered peptide ligand-induced
      apoptosis programmed by initial Ag receptor engagement.

PMID- 20139281
TI  - Streptococcus ursoris sp. nov., isolated from the oral cavities of bears.
AB  - Three Gram-positive, catalase-negative, coccus-shaped organisms were isolated
      from the oral cavities of bears. The isolates were tentatively identified as a
      streptococcal species based on the results of biochemical tests. Comparative 16S
      rRNA gene sequencing studies confirmed that the organisms were members of the
      genus Streptococcus, but they did not correspond to any recognized species of the
      genus. The nearest phylogenetic relative of the new isolates was Streptococcus
      ratti ATCC 19645(T) (98.6 %), however, DNA-DNA hybridization analysis showed that
      the isolates displayed less than 15 % DNA-DNA relatedness with the type strain of
      S. ratti. Colonies of the novel strains grown on mitis salivarius agar showed an
      extracellular polysaccharide-producing colony morphology. Based on phenotypic and
      phylogenetic evidence, it is proposed that the novel isolates are classified in
      the genus Streptococcus as Streptococcus ursoris sp. nov. The type strain of S.
      ursoris is NUM 1615(T) (=JCM 16316(T)=DSM 22768(T)).

PMID- 20139282
TI  - Proposal of Mingxiaea gen. nov. for the anamorphic basidiomycetous yeast species
      in the Bulleribasidium clade (Tremellales) based on molecular phylogenetic
      analysis, with six new combinations and four novel species.
AB  - The distinction and monophyletic property of the basidiomycetous yeast species in
      the Bulleribasidium clade of the order Tremellales was resolved by molecular
      phylogenetic analysis based on the combined sequences of the 18S rRNA gene,
      internal transcribed spacer (ITS) region including 5.8S rRNA gene and 26S rRNA
      gene D1/D2 domain. The addition to the clade of new anamorphic species identified
      among ballistoconidium-forming yeasts isolated from China confirmed and
      strengthened the separation of this clade from other clades or lineages in the
      order Tremellales. A new anamorphic genus, Mingxiaea gen. nov. (type species
      Mingxiaea variabilis comb. nov.) is therefore proposed to accommodate the
      anamorphic species in the Bulleribasidium clade. Six new combinations are
      proposed for the described species of this clade which were formerly assigned to
      the genus Bullera. Four novel species in the new genus were identified among 16
      ballistoconidium-forming yeast strains isolated from plant leaves collected in
      Hainan province, southern China, by D1/D2 and ITS sequence analyses. The novel
      species are described as Mingxiaea sanyaensis sp. nov. (type strain SY-3.23(T)
      =AS 2. 3623(T) =CBS 11408(T)), Mingxiaea hainanensis (type strain WZS-8.13(T) =AS
      2.4161(T) =CBS 11409(T)), Mingxiaea foliicola (type strain WZS-8.14(T) =AS
      2.3518(T) =CBS 11407(T)) and Mingxiaea wuzhishanensis (type strain WZS-29.8(T)
      =AS 2.4163(T) =CBS 11411(T)).

PMID- 20139283
TI  - Scardovia wiggsiae sp. nov., isolated from the human oral cavity and clinical
      material, and emended descriptions of the genus Scardovia and Scardovia
      inopinata.
AB  - Six strains of anaerobic, pleomorphic Gram-positive bacilli, isolated from the
      human oral cavity and an infected arm wound, were subjected to a comprehensive
      range of phenotypic and genotypic tests and were found to comprise a homogeneous
      group. 16S rRNA gene sequence analysis revealed that the isolates were most
      closely related to Scardovia inopinata CCUG 35729(T) (94.8-94.9 % 16S rRNA gene
      sequence similarity). The isolates were saccharolytic and produced acetic and
      lactic acids as end products of fermentation. The major fatty acids were C(16 :
      0) (49.8 %) and C(18 : 1)omega9c (35.8 %). Polar lipid analysis revealed a
      variety of glycolipids, diphosphatidylglycerol, an unidentified phospholipid and
      an unidentified phosphoglycolipid. No respiratory quinones were detected. The
      peptidoglycan was of the type A4alpha L-Lys-Thr-Glu, with L-lysine partially
      replaced by L-ornithine. The DNA G+C content of one of the strains, C1A_55(T)(,)
      was 55 mol%. A novel species, Scardovia wiggsiae sp. nov., is proposed to
      accommodate the six isolates, with the type strain C1A_55(T) (=DSM 22547(T)=CCUG
      58090(T)).

PMID- 20139284
TI  - Larkinella bovis sp. nov., isolated from fermented bovine products, and emended
      descriptions of the genus Larkinella and of Larkinella insperata Vancanneyt et
      al. 2006.
AB  - A novel bacterial strain, designated M2T2B15(T), was isolated from fermented
      bovine products and was characterized by using a polyphasic approach. Colonies
      were reddish pink and circular with entire margins. Cells were strictly aerobic,
      Gram-reaction-negative, oxidase- and catalase-positive rods that lacked flagella
      and were motile by gliding. Flexirubin-type pigments were absent. 16S rRNA gene
      sequence analysis indicated that strain M2T2B15(T) was related most closely to
      Larkinella insperata LMG 22510(T) (94.4 % similarity) but shared <87 % similarity
      with other members of the phylum Bacteroidetes. The major cellular fatty acids
      were C(16 : 1)omega5c, iso-C(15 : 0) and iso-C(17 : 0) 3-OH. The polar lipids
      were phosphatidylethanolamine, phosphatidylserine, two unidentified
      aminophospholipids and two unidentified polar lipids. Menaquinone 7 (MK-7) was
      the major respiratory quinone. The G+C content of the DNA of strain M2T2B15(T)
      was 52&emsp14;mol%. The phenotypic, genotypic and phylogenetic data presented
      clearly indicate that strain M2T2B15(T) represents a novel species of the genus
      Larkinella, for which the name Larkinella bovis sp. nov. is proposed. The type
      strain is M2T2B15(T) (=KACC 14040(T) =NBRC 106324(T)). Emended descriptions of
      the genus Larkinella and of Larkinella insperata Vancanneyt et al. 2006 are also
      proposed.

PMID- 20139287
TI  - Combination therapy with verteporfin and anti-VEGF agents in neovascular age
      related macular degeneration: where do we stand?

PMID- 20139289
TI  - Z-suture: a new knotless technique for transscleral suture fixation of
      intraocular implants.
AB  - The presented Z-suture is a simple, rapid and safe knotless technique that
      facilitates transscleral suture fixation of various intraocular implants in the
      ciliary sulcus, such as sutured intraocular lenses, artificial iris prostheses
      and iris diaphragms. As the knotless approach reliably avoids suture erosion,
      external fixation can be performed without any protecting scleral flaps or
      lamellar grooves. The needle is simply passed through the sulcus and the emerging
      polypropylene suture is secured in the sclera using a zigzag-shaped intrascleral
      suture (Z-suture). Each pass starts directly adjacent to the exiting site. Five
      passes are sufficient to reliably fix the suture so that it resists even maximum
      tractive forces. Once this procedure is done, the suture can be cut without any
      knot. By avoiding suture knots, and hence the need for intrascleral flaps, this
      knotless approach may help to reduce suture-related complications such as scleral
      atrophy, suture erosion and infections.

PMID- 20139290
TI  - Transcleral delivery of triamcinolone acetonide and ranibizumab to retinal
      tissues using macroesis.
AB  - AIM: To determine the feasibility of macroesis for the delivery of ranibizumab
      and triamcinolone acetonide via a transcleral route. METHODS: Macroesis is a non
      invasive method of drug delivery that uses alternating current (AC) to deliver
      drugs to target tissues. Two preclinical models of drug delivery were used for
      feasibility studies of delivering ranibizumab and triamcinolone acetonide to
      ocular tissues. In the first model, full-thickness sections of rabbit ocular
      tissue (conjunctiva to retina) were placed on an interdigitated electrode
      platform, and the drug was placed on the surface of the tissue. A non-uniform
      electrical field was applied to the ocular tissue, and electrical conductivity, a
      measurement of drug delivery, was monitored during the course of the experiment.
      In a second model, termed a 'simulated vitreous model,' the same full-thickness
      sections of rabbit ocular tissue were mounted below the electrode device, and the
      test compounds were placed on the electrodes. The fluid below the tissue, which
      simulated the vitreous cavity, was analysed using UV spectroscopy at the end of
      the study for the presence of drug. RESULTS: In the electrical conductivity
      studies, the electric characteristics of the tissue-drug system clearly showed
      movement of the drug through the tissue to the dielectric sensor based on changes
      in the electrical conductivity of the tissue sample with triamcinolone. No change
      in tissue conductivity was observed when no drug was placed. No heat generation
      occurred during the course of the study; nor was any gross tissue destruction
      noted. In the simulated vitreous model, studies using triamcinolone yielded
      concentrations ranging from 0.280 to 0.970 mg/ml, depending on the voltage,
      frequency and time applied. In as little as 6.7 min, clinically efficacious doses
      could be obtained in the preclinical system. Studies using ranibizumab yielded
      concentrations of 0.070-0.171 mg/ml, depending on the voltage, frequency, and
      time applied. In as little at 6.7 min, 92.8% throughput could be achieved.
      CONCLUSION: Successful delivery of ranibizumab and triamcinolone acetonide can be
      achieved with macroesis in preclinical studies.

PMID- 20139291
TI  - Vision self-management for older adults: a randomised controlled trial.
AB  - BACKGROUND/AIMS: Ageing of the population will result in unprecedented numbers of
      older adults living with age-related vision loss (ARVL). Self-management models
      improve health outcomes and reduce healthcare costs; however, the principles have
      rarely been applied in low vision services. METHODS: A two-armed randomised
      controlled trial of older adults (n=77) with ARVL compared 'usual care' provided
      by a not-for-profit community agency with an extended model of care (usual
      care+self-management group intervention). The primary outcome variable
      (participation in life situations) was measured using the Activity Card Sort.
      Secondary outcome measures examined general health and vision-specific domains.
      RESULTS: The intention-to-treat analysis demonstrated that the extended model
      produced significantly better participation in life situations at post-test when
      compared with the usual care only group. Gains were made regardless of whether
      participants were, or were not, depressed at baseline. The addition of the self
      management group was also successful in significantly reducing depression,
      increasing physical and mental health, generalised and domain-specific self
      efficacy, and adjustment to ARVL. With the exception of adjustment and mental
      health, differences were still apparent at 12 weeks' follow-up. CONCLUSION:
      Addition of self-management significantly improved general health and vision
      specific rehabilitation outcomes for older adults with ARVL.

PMID- 20139292
TI  - Photorefractive keratectomy for the treatment of purely refractive accommodative
      esotropia: 6 years' experience.
AB  - AIMS: To report the long term outcomes of photorefractive keratectomy (PRK) for
      the treatment of hyperopia associated with purely refractive accommodative
      esotropia. METHODS: This study was a retrospective chart review of 40 patients
      aged 17-39 years who underwent PRK to eliminate their dependence on glasses. Pre-
      and postoperative best spectacle corrected visual acuity (BSCVA), uncorrected
      visual acuity (UCVA), refractive spherical equivalent (SEQ), ocular alignment and
      stereoacuity were reviewed. RESULTS: Forty patients (80 eyes) with a mean age of
      27.9 years were treated for a mean preoperative SEQ of +3.06 D hyperopia. The
      mean final postoperative SEQ was +0.06 D. Preoperative BSCVA was 0.04 logarithm
      of the minimum angle of resolution (logMAR), and did not change postoperatively.
      Mean UCVA significantly improved from 0.30 logMAR preoperatively to 0.08 logMAR
      post-operatively. Mean pre-operative esotropia at distance and near was 18.6
      prism D. All patients were orthophoric without correction at the 1 month, 1 year
      and final postoperative evaluations. Visual acuity, refractive error and
      alignment remained stable after the 1 year postoperative examination.
      Stereoacuity was unchanged in 80% of patients postoperatively. There were no
      complications. CONCLUSION: PRK can be used to treat low to moderate hyperopia
      associated with purely refractive accommodative esotropia in young adults.

PMID- 20139293
TI  - Management of submacular haemorrhage in age-related macular degeneration with
      intravitreal tenecteplase.

PMID- 20139294
TI  - Primary epithelioid haemangioendothelioma of the eyelid.

PMID- 20139295
TI  - In vivo corneal confocal microscopic findings and gene analysis of three patients
      with Thiel-Behnke corneal dystrophy.

PMID- 20139296
TI  - Presence of paravascular lamellar holes in patients with idiopathic premacular
      fibrosis.

PMID- 20139297
TI  - Neurodevelopmental outcomes with congenital ocular motor apraxia.

PMID- 20139298
TI  - Endothelial cells analysis after intravitreal ranibizumab (Lucentis) in age
      related macular degeneration treatment: a pilot study.

PMID- 20139299
TI  - The photonic "smart grid" of the chloroplast in action.

PMID- 20139300
TI  - Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor-dependent
      signaling pathways in renal collecting duct cells.
AB  - Vasopressin's action in renal cells to regulate water transport depends on
      protein phosphorylation. Here we used mass spectrometry-based quantitative
      phosphoproteomics to identify signaling pathways involved in the short-term V2
      receptor-mediated response in cultured collecting duct cells (mpkCCD) from mouse.
      Using Stable Isotope Labeling by Amino acids in Cell culture (SILAC) with two
      treatment groups (0.1 nM dDAVP or vehicle for 30 min), we carried out
      quantification of 2884 phosphopeptides. The majority (82%) of quantified
      phosphopeptides did not change in abundance in response to dDAVP. Analysis of the
      273 phosphopeptides increased by dDAVP showed a predominance of so-called
      "basophilic" motifs consistent with activation of kinases of the AGC family.
      Increases in phosphorylation of several known protein kinase A targets were
      found. In addition, increased phosphorylation of targets of the calmodulin
      dependent kinase family was seen, including autophosphorylation of calmodulin
      dependent kinase 2 at T286. Analysis of the 254 phosphopeptides decreased in
      abundance by dDAVP showed a predominance of so-called "proline-directed" motifs,
      consistent with down-regulation of mitogen-activated or cyclin-dependent kinases.
      dDAVP decreased phosphorylation of both JNK1/2 (T183/Y185) and ERK1/2 (T183/Y185;
      T203/Y205), consistent with a decrease in activation of these proline-directed
      kinases in response to dDAVP. Both ERK and JNK were able to phosphorylate residue
      S261of aquaporin-2 in vitro, a site showing a decrease in phosphorylation in
      response to dDAVP in vivo. The data support roles for multiple vasopressin V2
      receptor-dependent signaling pathways in the vasopressin signaling network of
      collecting duct cells, involving several kinases not generally accepted to
      regulate collecting duct function.

PMID- 20139301
TI  - Complete HOX cluster characterization of the coelacanth provides further evidence
      for slow evolution of its genome.
AB  - The living coelacanth is a lobe-finned fish that represents an early evolutionary
      departure from the lineage that led to land vertebrates, and is of extreme
      interest scientifically. It has changed very little in appearance from fossilized
      coelacanths of the Cretaceous (150 to 65 million years ago), and is often
      referred to as a "living fossil." An important general question is whether long
      term stasis in morphological evolution is associated with stasis in genome
      evolution. To this end we have used targeted genome sequencing for acquiring
      1,612,752 bp of high quality finished sequence encompassing the four HOX clusters
      of the Indonesian coelacanth Latimeria menadoensis. Detailed analyses were
      carried out on genomic structure, gene and repeat contents, conserved noncoding
      regions, and relative rates of sequence evolution in both coding and noncoding
      tracts. Our results demonstrate conclusively that the coelacanth HOX clusters are
      evolving comparatively slowly and that this taxon should serve as a viable
      outgroup for interpretation of the genomes of tetrapod species.

PMID- 20139302
TI  - Close association of RNA polymerase II and many transcription factors with Pol
      III genes.
AB  - Transcription of the eukaryotic genomes is carried out by three distinct RNA
      polymerases I, II, and III, whereby each polymerase is thought to independently
      transcribe a distinct set of genes. To investigate a possible relationship of RNA
      polymerases II and III, we mapped their in vivo binding sites throughout the
      human genome by using ChIP-Seq in two different cell lines, GM12878 and K562
      cells. Pol III was found to bind near many known genes as well as several
      previously unidentified target genes. RNA-Seq studies indicate that a majority of
      the bound genes are expressed, although a subset are not suggestive of stalling
      by RNA polymerase III. Pol II was found to bind near many known Pol III genes,
      including tRNA, U6, HVG, hY, 7SK and previously unidentified Pol III target
      genes. Similarly, in vivo binding studies also reveal that a number of
      transcription factors normally associated with Pol II transcription, including c
      Fos, c-Jun and c-Myc, also tightly associate with most Pol III-transcribed genes.
      Inhibition of Pol II activity using alpha-amanitin reduced expression of a number
      of Pol III genes (e.g., U6, hY, HVG), suggesting that Pol II plays an important
      role in regulating their transcription. These results indicate that, contrary to
      previous expectations, polymerases can often work with one another to globally
      coordinate gene expression.

PMID- 20139303
TI  - Genetic discontinuity of big fish in a small sea.

PMID- 20139304
TI  - Arabidopsis IWS1 interacts with transcription factor BES1 and is involved in
      plant steroid hormone brassinosteroid regulated gene expression.
AB  - Plant steroid hormones, brassinosteroids (BRs), regulate essential growth and
      developmental processes. BRs signal through membrane-localized receptor BRI1 and
      several other signaling components to regulate the BES1 and BZR1 family
      transcription factors, which in turn control the expression of hundreds of target
      genes. However, knowledge about the transcriptional mechanisms by which BES1/BZR1
      regulate gene expression is limited. By a forward genetic approach, we have
      discovered that Arabidopsis thaliana Interact-With-Spt6 (AtIWS1), an
      evolutionarily conserved protein implicated in RNA polymerase II (RNAPII)
      postrecruitment and transcriptional elongation processes, is required for BR
      induced gene expression. Loss-of-function mutations in AtIWS1 lead to overall
      dwarfism in Arabidopsis, reduced BR response, genome-wide decrease in BR-induced
      gene expression, and hypersensitivity to a transcription elongation inhibitor.
      Moreover, AtIWS1 interacts with BES1 both in vitro and in vivo. Chromatin
      immunoprecipitation experiments demonstrated that the presence of AtIWS1 is
      enriched in transcribed as well as promoter regions of the target genes under BR
      induced conditions. Our results suggest that AtIWS1 is recruited to target genes
      by BES1 to promote gene expression during transcription elongation process.
      Recent genomic studies have indicated that a large number of genes could be
      regulated at steps after RNAPII recruitment; however, the mechanisms for such
      regulation have not been well established. The study therefore not only
      establishes an important role for AtIWS1 in plant steroid-induced gene expression
      but also suggests an exciting possibility that IWS1 protein can function as a
      target for pathway-specific activators, thereby providing a unique mechanism for
      the control of gene expression.

PMID- 20139305
TI  - Genomic code for Sox10 activation reveals a key regulatory enhancer for cranial
      neural crest.
AB  - The neural crest is a multipotent, stem cell-like population that migrates
      extensively in the embryo and forms a wide array of derivatives, ranging from
      neurons to melanocytes and cartilage. Analyses of the gene regulatory network
      driving neural crest development revealed Sox10 as one of the earliest neural
      crest-specifying genes, cell-autonomously driving delamination and directly
      regulating numerous downstream effectors and differentiation gene batteries. In
      search of direct inputs to the neural crest specifier module, we dissected the
      chick Sox10 genomic region and isolated two downstream regulatory regions with
      distinct spatiotemporal activity. A unique element, Sox10E2 represents the
      earliest-acting neural crest cis-regulatory element, critical for initiating
      Sox10 expression in newly formed cranial, but not vagal and trunk neural crest. A
      second element, Sox10E1, acts in later migrating vagal and trunk crest cells.
      Deep characterization of Sox10E2 reveals Sox9, Ets1, and cMyb as direct inputs
      mediating enhancer activity. ChIP, DNA-pull down, and gel-shift assays
      demonstrate their direct binding to the Sox10E2 enhancer in vivo, whereas
      mutation of their corresponding binding sites, or inactivation of the three
      upstream regulators, abolishes both reporter and endogenous Sox10 expression.
      Using cis-regulatory analysis as a tool, our study makes critical connections
      within the neural crest gene regulatory network, thus being unique in
      establishing a direct link of upstream effectors to a key neural crest specifier.

PMID- 20139306
TI  - Intrinsic reactivity and driving force dependence in concerted proton-electron
      transfers to water illustrated by phenol oxidation.
AB  - Three experimental techniques, laser flash photolysis, redox catalysis, and
      stopped-flow, were used to investigate the variation of the oxidation rate
      constant of phenol in neat water with the driving force offered by a series of
      electron acceptors. Taking into account a result previously obtained with a low
      driving force electron acceptor thus allowed scanning more than half an electron
      volt driving force range. Variation of the rate constant with pH showed the
      transition between a direct phenol oxidation reaction at low pH, where the rate
      constant does not vary with pH, and a stepwise reaction involving the prior
      deprotonation of phenol by OH(-), characterized by a unity-slope variation.
      Analyses of the direct oxidation kinetics, based on its variation with the
      driving force and on the determination of H/D isotope effects, ruled out a
      stepwise mechanism in which electron transfer is followed by the deprotonation of
      the initial cation radical at the benefit of a pathway in which proton and
      electron are transferred concertedly. Derivation of the characteristics of
      counterdiffusion in termolecular reactions allowed showing that the concerted
      process is under activation control. It is characterized by a remarkably small
      reorganization energy, in line with the electrochemical counterpart of the
      reaction, underpinning the very peculiar behavior of water as proton acceptor
      when it is used as the solvent.

PMID- 20139307
TI  - Biofilm formation by Campylobacter jejuni is increased under aerobic conditions.
AB  - The microaerophilic human pathogen Campylobacter jejuni is the leading cause of
      food-borne bacterial gastroenteritis in the developed world. During transmission
      through the food chain and the environment, the organism must survive stressful
      environmental conditions, particularly high oxygen levels. Biofilm formation has
      been suggested to play a role in the environmental survival of this organism. In
      this work we show that C. jejuni NCTC 11168 biofilms developed more rapidly under
      environmental and food-chain-relevant aerobic conditions (20% O(2)) than under
      microaerobic conditions (5% O(2), 10% CO(2)), although final levels of biofilms
      were comparable after 3 days. Staining of biofilms with Congo red gave results
      similar to those obtained with the commonly used crystal violet staining. The
      level of biofilm formation by nonmotile aflagellate strains was lower than that
      observed for the motile flagellated strain but nonetheless increased under
      aerobic conditions, suggesting the presence of flagellum-dependent and flagellum
      independent mechanisms of biofilm formation in C. jejuni. Moreover, preformed
      biofilms shed high numbers of viable C. jejuni cells into the culture supernatant
      independently of the oxygen concentration, suggesting a continuous passive
      release of cells into the medium rather than a condition-specific active
      mechanism of dispersal. We conclude that under aerobic or stressful conditions,
      C. jejuni adapts to a biofilm lifestyle, allowing survival under detrimental
      conditions, and that such a biofilm can function as a reservoir of viable
      planktonic cells. The increased level of biofilm formation under aerobic
      conditions is likely to be an adaptation contributing to the zoonotic lifestyle
      of C. jejuni.

PMID- 20139308
TI  - Probabilistic model for Listeria monocytogenes growth during distribution, retail
      storage, and domestic storage of pasteurized milk.
AB  - A survey on the time-temperature conditions of pasteurized milk in Greece during
      transportation to retail, retail storage, and domestic storage and handling was
      performed. The data derived from the survey were described with appropriate
      probability distributions and introduced into a growth model of Listeria
      monocytogenes in pasteurized milk which was appropriately modified for taking
      into account strain variability. Based on the above components, a probabilistic
      model was applied to evaluate the growth of L. monocytogenes during the chill
      chain of pasteurized milk using a Monte Carlo simulation. The model predicted
      that, in 44.8% of the milk cartons released in the market, the pathogen will grow
      until the time of consumption. For these products the estimated mean total growth
      of L. monocytogenes during transportation, retail storage, and domestic storage
      was 0.93 log CFU, with 95th and 99th percentiles of 2.68 and 4.01 log CFU,
      respectively. Although based on EU regulation 2073/2005 pasteurized milk produced
      in Greece belongs to the category of products that do not allow the growth of L.
      monocytogenes due to a shelf life (defined by law) of 5 days, the above results
      show that this shelf life limit cannot prevent L. monocytogenes from growing
      under the current chill chain conditions. The predicted percentage of milk
      cartons-initially contaminated with 1 cell/1-liter carton-in which the pathogen
      exceeds the safety criterion of 100 cells/ml at the time of consumption was
      0.14%. The probabilistic model was used for an importance analysis of the chill
      chain factors, using rank order correlation, while selected intervention and
      shelf life increase scenarios were evaluated. The results showed that simple
      interventions, such as excluding the door shelf from the domestic storage of
      pasteurized milk, can effectively reduce the growth of the pathogen. The door
      shelf was found to be the warmest position in domestic refrigerators, and it was
      most frequently used by the consumers for domestic storage of pasteurized milk.
      Furthermore, the model predicted that a combination of this intervention with a
      decrease of the mean temperature of domestic refrigerators by 2 degrees C may
      allow an extension of pasteurized milk shelf life from 5 to 7 days without
      affecting the current consumer exposure to L. monocytogenes.

PMID- 20139309
TI  - Population diversity of Listeria monocytogenes LO28: phenotypic and genotypic
      characterization of variants resistant to high hydrostatic pressure.
AB  - A comparative phenotype analysis of 24 Listeria monocytogenes LO28 stress
      resistant variants obtained after high-pressure treatment was performed to assess
      their robustness and growth performance under a range of food-relevant
      conditions. In addition, genetic analysis was conducted to characterize the
      promoter regions and open reading frames of the class I and III transcriptional
      repressors CtsR and HrcA, which control production of specific sets of stress
      proteins. Analysis of stress survival capacity, motility, biofilm formation, and
      growth under various conditions showed all variants to be more resistant to
      pressure and heat than the wild type; however, differences among variants were
      observed in acid resistance, growth rate, motility, and biofilm-forming capacity.
      Genetic analysis revealed no variation in the genetic make-up of hrcA and its
      upstream region, but two variants had deletions in the upstream region of ctsR
      and seven variants had mutations in the ctsR gene itself. The results of the
      characterization were cluster analyzed to obtain insight into the diversity of
      variants. Ten unique variants and three clusters with specific features could be
      identified: one cluster consisting of seven variants having a mutation in the
      CtsR regulator gene, one cluster containing two variants with an aerobic biofilm
      formation capacity similar to that of the wild type, and a cluster composed of
      five immotile variants. The large population diversity of L. monocytogenes stress
      resistant variants signifies the organism's genetic flexibility, which in turn
      may contribute to the survival and persistence of this human pathogen in food
      processing environments.

PMID- 20139310
TI  - Effects of Swine manure on macrolide, lincosamide, and streptogramin B
      antimicrobial resistance in soils.
AB  - Current agricultural practices involve inclusion of antimicrobials in animal feed
      and result in manure containing antimicrobials and antimicrobial-resistant
      microorganisms. This work evaluated the effects of land application of swine
      manure on the levels of tetracycline, macrolide, and lincosamide antimicrobials
      and on macrolide, lincosamide, and streptogramin B (MLS(B)) resistance in field
      soil samples and laboratory soil batch tests. MLS(B) and tetracycline
      antimicrobials were quantified after solid-phase extraction using liquid
      chromatography-tandem mass spectrometry. The prevalence of the ribosomal
      modification responsible for MLS(B) resistance in the same samples was quantified
      using fluorescence in situ hybridization. Macrolide antimicrobials were not
      detected in soil samples, while tetracyclines were detected, suggesting that the
      latter compounds persist in soil. No significant differences in ribosomal
      methylation or presumed MLS(B) resistance were observed when amended and
      unamended field soils were compared, although a transient (<20-day) increase was
      observed in most batch tests. Clostridium cluster XIVa accounted for the largest
      fraction of resistant bacteria identified in amended soils. Overall, this study
      did not detect a persistent increase in the prevalence of MLS(B) resistance due
      to land application of treated swine manure.

PMID- 20139311
TI  - Rickettsia felis infection in a common household insect pest, Liposcelis
      bostrychophila (Psocoptera: Liposcelidae).
AB  - Many species of Rickettsia are well-known mammalian pathogens transmitted by
      blood-feeding arthropods. However, molecular surveys are continually uncovering
      novel Rickettsia species, often in unexpected hosts, including many arthropods
      that do not feed on blood. This study reports a systematic molecular
      characterization of a Rickettsia infecting the psocid Liposcelis bostrychophila
      (Psocoptera: Liposcelidae), a common and cosmopolitan household pest.
      Surprisingly, the psocid Rickettsia is shown to be Rickettsia felis, a human
      pathogen transmitted by fleas that causes serious morbidity and occasional
      mortality. The plasmid from the psocid R. felis was sequenced and was found to be
      virtually identical to the one in R. felis from fleas. As Liposcelis insects are
      often intimately associated with humans and other vertebrates, it is speculated
      that they acquired R. felis from fleas. Whether the R. felis in psocids causes
      disease in vertebrates is not known and warrants further study.

PMID- 20139312
TI  - High-throughput method for rapid induction of prophages from lysogens and its
      application in the study of Shiga Toxin-encoding Escherichia coli strains.
AB  - A high-throughput 96-well plate-based method for the rapid induction of
      endogenous prophages from individual bacterial strains was developed. The
      detection of endogenous prophages was achieved by the filtration of the culture
      liquor following norfloxacin induction and subsequent PCRs targeting
      bacteriophage-carried gene markers. The induction method was tested on 188
      putative Shiga toxin (Stx)-producing Escherichia coli (STEC) strains and
      demonstrated the ability to detect both lambdoid and stx-carrying bacteriophages
      in strains for which plaques were not observed via plaque assay. Lambdoid
      bacteriophages were detected in 37% of the induced phage preparations via
      amplification of the Q gene, and Stx1- and Stx2-encoding phages were detected in
      2 and 14% of the strains, respectively. The method therefore provided greater
      sensitivity for the detection of Stx and other lambdoid bacteriophage populations
      carried by STEC strains than that for the established method of plaque assay
      using bacterial indicator strains, enabling, for the first time, large-scale
      bacteriophage population and diversity studies.

PMID- 20139313
TI  - Requirement of a mitogen-activated protein kinase for appressorium formation and
      penetration of insect cuticle by the entomopathogenic fungus Beauveria bassiana.
AB  - Beauveria bassiana is an important insect-pathogenic fungus that invades insects
      by direct penetration of the host cuticle. To delineate the molecular mechanisms
      involved in fungal infection, a mitogen-activated protein kinase (MAPK) gene,
      Bbmpk1, which encodes a YERK1 family MAPK was isolated and characterized.
      Targeted gene disruption of Bbmpk1 resulted in a complete loss of virulence when
      applied topically to host insects but did not affect growth of the fungus when
      conidia were injected directly into the hemocoel. Hyphae of the mutant strain
      growing in the insect hemocoel were unable to penetrate the cuticle growing
      outwards and consequently failed to sporulate on the cadaver surface. These data
      suggest that BbMPK1 is essential for penetration of the insect cuticle both from
      the outside and from the inside-out in order to escape and disperse from the
      host. Inactivation of BbMPK1 also caused a significant decrease in fungal
      adhesion to insect cuticles and eliminated their ability to form appressoria. In
      order to identify downstream genes regulated by BbMPK1, a suppressive subtractive
      hybridization (SSH) library was generated comparing mutant and wild-type
      transcripts isolated during appressorium formation. Thirty-one genes screened
      from the SSH library were determined to be expressed in the wild-type strain but
      either significantly reduced or not expressed in the mutant. Ten genes showed
      high or medium similarity to known protein encoding genes, including proteins
      involved in cell surface hydrophobicity, lipid metabolism, microtubule dynamics,
      mitochondrial electron transport, chromatin remodeling, transcription, rRNA
      processing, small nucleolar RNA accumulation, oxidation of aldehydes,
      translation, and likely other cellular processes.

PMID- 20139314
TI  - Identification of ciliate grazers of autotrophic bacteria in ammonia-oxidizing
      activated sludge by RNA stable isotope probing.
AB  - It is well understood that protozoa play a major role in controlling bacterial
      biomass and regulating nutrient cycling in the environment. Little is known,
      however, about the movement of carbon from specific reduced substrates, through
      functional groups of bacteria, to particular clades of protozoa. In this study we
      first identified the active protozoan phylotypes present in activated sludge, via
      the construction of an rRNA-derived eukaryote clone library. Most of the
      sequences identified belonged to ciliates of the subclass Peritrichia and
      amoebae, confirming the dominance of surface-associated protozoa in the activated
      sludge environment. We then demonstrated that (13)C-labeled protozoan RNA can be
      retrieved from activated sludge amended with (13)C-labeled protozoa or (13)C
      labeled Escherichia coli cells by using an RNA stable isotope probing (RNA-SIP)
      approach. Finally, we used RNA-SIP to track carbon from bicarbonate and acetate
      into protozoa under ammonia-oxidizing and denitrifying conditions, respectively.
      RNA-SIP analysis revealed that the peritrich ciliate Epistylis galea dominated
      the acquisition of carbon from bacteria with access to CO(2) under ammonia
      oxidizing conditions, while there was no evidence of specific grazing on acetate
      consumers under denitrifying conditions.

PMID- 20139315
TI  - Enhancement of enteric adenovirus cultivation by viral transactivator proteins.
AB  - Human enteric adenoviruses (HAdVs; serotypes 40 and 41) are important waterborne
      and food-borne pathogens. However, HAdVs are fastidious, are difficult to
      cultivate, and do not produce a clear cytopathic effect during cell culture
      within a reasonable time. Thus, we examined whether the viral transactivator
      proteins cytomegalovirus (CMV) IE1 and hepatitis B virus (HBV) X promoted the
      multiplication of HAdVs. Additionally, we constructed a new 293 cell line
      expressing CMV IE1 protein for cultivation assays. We analyzed the nucleic acid
      sequences of the promoter regions of both E1A and hexon genes, which are
      considered to be the most important regions for HAdV replication. Expression of
      either HBV X or CMV IE1 protein significantly increased the promoter activities
      of E1A and hexon genes of HAdVs by as much as 14-fold during cell cultivation.
      The promotion of HAdV expression was confirmed by increased levels of both
      adenoviral DNA and mRNA expression. Finally, the newly developed 293 cell line
      expressing CMV IE1 protein showed an increase in viral DNA ranging from 574% to
      619% compared with the conventional 293 cell line. These results suggest that the
      newly constructed cell line could be useful for efficient cultivation and
      research of fastidious HAdVs.

PMID- 20139316
TI  - Characterization of the Aspergillus nidulans monodictyphenone gene cluster.
AB  - Deletion of cclA, a component of the COMPASS complex of Aspergillus nidulans,
      results in the production of monodictyphenone and emodin derivatives. Through a
      set of targeted deletions in a cclA deletion strain, we have identified the genes
      required for monodictyphenone and emodin analog biosynthesis. Identification of
      an intermediate, endocrocin, from an mdpHDelta strain suggests that mdpH might
      encode a decarboxylase. Furthermore, by replacing the promoter of mdpA (a
      putative aflJ homolog) and mdpE (a putative aflR homolog) with the inducible alcA
      promoter, we have confirmed that MdpA functions as a coactivator. We propose a
      biosynthetic pathway for monodictyphenone and emodin derivatives based on
      bioinformatic analysis and characterization of biosynthetic intermediates.

PMID- 20139317
TI  - Negative effects of sample pooling on PCR-based estimates of soil microbial
      richness and community structure.
AB  - In this study, we examined the effect of various pooling strategies on the
      characterization of soil microbial community composition and phylotype richness
      estimates. Automated ribosomal intergenic spacer analysis (ARISA) profiles were
      determined from soil samples that were (i) unpooled (extracted and amplified
      individually), (ii) pooled prior to PCR amplification, or (iii) pooled prior to
      DNA extraction. Regression analyses suggest that the less even the soil microbial
      community (i.e., low Shannon equitability, E(H)), the greater was the impact of
      either pooling strategy on microbial detection (R(2) = 0.766). For example, at a
      tropical rainforest site, which had the most uneven fungal (E(H) of 0.597) and
      bacterial communities (E(H) of 0.822), the unpooled procedure detected an
      additional 67 fungal and 115 bacterial phylotypes relative to either of the
      pooled procedures. Phylotype rarity, resulting in missed detection upon pooling,
      differed between the fungal and bacterial communities. Fungi were typified by
      locally abundant but spatially rare phylotypes, and the bacteria were typified by
      locally rare but spatially ubiquitous phylotypes. As a result, pooling
      differentially influenced plot comparisons, leading to an increase in similarity
      for the bacterial community and a decrease in the fungal community. In
      conclusion, although pooling reduces sample numbers and variability, it could
      mask a significant portion of the detectable microbial community, particularly
      for fungi due to their higher spatial heterogeneity.

PMID- 20139318
TI  - Quantification of burkholderia coxL genes in Hawaiian volcanic deposits.
AB  - Isolation of multiple carbon monoxide (CO)-oxidizing Burkholderia strains and
      detection by culture-independent approaches suggest that Burkholderia may be an
      important component of CO-oxidizing communities in Hawaiian volcanic deposits.
      The absolute and relative abundance of the bacteria in these communities remains
      unknown, however. In this study, a quantitative PCR (Q-PCR) approach has been
      developed to enumerate Burkholderia coxL genes (large subunit of carbon monoxide
      dehydrogenase). This represents the first attempt to enumerate coxL genes from CO
      oxidizers in environmental samples. coxL copy numbers have been determined for
      samples from three sites representing a vegetation gradient on a 1959 volcanic
      deposit that included unvegetated cinders (bare), edges of vegetated sites
      (edge), and sites within tree stands (canopy). Q-PCR has also been used to
      estimate copy numbers of Betaproteobacteria 16S rRNA gene copy numbers and total
      Bacteria 16S rRNA. coxL genes could not be detected in the bare site (detection
      limit, > or = 4.7 x 10(3) copies per reaction) but average 1.0 x 10(8) + or - 2.4
      x 10(7) and 8.6 x 10(8) + or - 7.6 x 10(7) copies g(-1) (dry weight) in edge and
      canopy sites, respectively, which differ statistically (P = 0.0007). Average
      Burkholderia coxL gene copy numbers, expressed as a percentage of total Bacteria
      16S rRNA gene copy numbers, are 6.2 and 0.7% for the edge and canopy sites,
      respectively. Although the percentage of Burkholderia coxL is lower in the canopy
      site, significantly greater gene copy numbers demonstrate that absolute abundance
      of coxL increases in vegetated sites and contributes to the expansion of CO
      oxidizer communities during biological succession on volcanic deposits.

PMID- 20139319
TI  - Role of extracellular DNA during biofilm formation by Listeria monocytogenes.
AB  - Listeria monocytogenes is a food-borne pathogen that is capable of living in
      harsh environments. It is believed to do this by forming biofilms, which are
      surface-associated multicellular structures encased in a self-produced matrix. In
      this paper we show that in L. monocytogenes extracellular DNA (eDNA) may be the
      only central component of the biofilm matrix and that it is necessary for both
      initial attachment and early biofilm formation for 41 L. monocytogenes strains
      that were tested. DNase I treatment resulted in dispersal of biofilms, not only
      in microtiter tray assays but also in flow cell biofilm assays. However, it was
      also demonstrated that in a culture without eDNA, neither Listeria genomic DNA
      nor salmon sperm DNA by itself could restore the capacity to adhere. A search for
      additional necessary components revealed that peptidoglycan (PG), specifically N
      acetylglucosamine (NAG), interacted with the DNA in a manner which restored
      adhesion. If a short DNA fragment (less than approximately 500 bp long) was added
      to an eDNA-free culture prior to addition of genomic or salmon sperm DNA,
      adhesion was prevented, indicating that high-molecular-weight DNA is required for
      adhesion and that the number of attachment sites on the cell surface can be
      saturated.

PMID- 20139320
TI  - Two types of endosymbiotic bacteria in the enigmatic marine worm Xenoturbella
      bocki.
AB  - Two types of endosymbiotic bacteria were identified in the gastrodermis of the
      marine invertebrate Xenoturbella bocki (Xenoturbellida, Bilateria). While
      previously described Chlamydia-like endosymbionts were rare, Gammaproteobacteria
      distantly related to other endosymbionts and pathogens were abundant. The
      endosymbionts should be considered when interpreting the poorly understood
      ecology and evolution of Xenoturbella.

PMID- 20139321
TI  - Detection and quantification of functional genes of cellulose- degrading,
      fermentative, and sulfate-reducing bacteria and methanogenic archaea.
AB  - Cellulose degradation, fermentation, sulfate reduction, and methanogenesis are
      microbial processes that coexist in a variety of natural and engineered anaerobic
      environments. Compared to the study of 16S rRNA genes, the study of the genes
      encoding the enzymes responsible for these phylogenetically diverse functions is
      advantageous because it provides direct functional information. However, no
      methods are available for the broad quantification of these genes from uncultured
      microbes characteristic of complex environments. In this study, consensus
      degenerate hybrid oligonucleotide primers were designed and validated to amplify
      both sequenced and unsequenced glycoside hydrolase genes of cellulose-degrading
      bacteria, hydA genes of fermentative bacteria, dsrA genes of sulfate-reducing
      bacteria, and mcrA genes of methanogenic archaea. Specificity was verified in
      silico and by cloning and sequencing of PCR products obtained from an
      environmental sample characterized by the target functions. The primer pairs were
      further adapted to quantitative PCR (Q-PCR), and the method was demonstrated on
      samples obtained from two sulfate-reducing bioreactors treating mine drainage,
      one lignocellulose based and the other ethanol fed. As expected, the Q-PCR
      analysis revealed that the lignocellulose-based bioreactor contained higher
      numbers of cellulose degraders, fermenters, and methanogens, while the ethanol
      fed bioreactor was enriched in sulfate reducers. The suite of primers developed
      represents a significant advance over prior work, which, for the most part, has
      targeted only pure cultures or has suffered from low specificity. Furthermore,
      ensuring the suitability of the primers for Q-PCR provided broad quantitative
      access to genes that drive critical anaerobic catalytic processes.

PMID- 20139322
TI  - Inhibition of telomerase activity alters tight junction protein expression and
      induces transendothelial migration of HIV-1-infected cells.
AB  - Telomerase, via its catalytic component telomerase reverse transcriptase (TERT),
      extends telomeres of eukaryotic chromosomes. The importance of this reaction is
      related to the fact that telomere shortening is a rate-limiting mechanism for
      human life span that induces cell senescence and contributes to the development
      of age-related pathologies. The aim of the present study was to evaluate whether
      the modulation of telomerase activity can influence human immunodeficiency virus
      type 1 (HIV-1)-mediated dysfunction of human brain endothelial cells (hCMEC/D3
      cells) and transendothelial migration of HIV-1-infected cells. Telomerase
      activity was modulated in hCMEC/D3 cells via small interfering RNA-targeting
      human TERT (hTERT) or by using a specific pharmacological inhibitor of
      telomerase, TAG-6. The inhibition of hTERT resulted in the upregulation of HIV-1
      induced overexpression of intercellular adhesion molecule-1 via the nuclear
      factor-kappaB-regulated mechanism and induced the transendothelial migration of
      HIV-1-infected monocytic U937 cells. In addition, the blocking of hTERT activity
      potentiated a HIV-induced downregulation of the expression of tight junction
      proteins. These results were confirmed in TERT-deficient mice injected with HIV-1
      specific protein Tat into the cerebral vasculature. Further studies revealed that
      the upregulation of matrix metalloproteinase-9 is the underlying mechanisms of
      disruption of tight junction proteins in hCMEC/D3 cells with inhibited TERT and
      exposed to HIV-1. These results indicate that the senescence of brain endothelial
      cells may predispose to the HIV-induced upregulation of inflammatory mediators
      and the disruption of the barrier function at the level of the brain endothelium.

PMID- 20139323
TI  - Ventricular function and natriuretic peptides in sequentially combined models of
      hypertension.
AB  - Hemodynamic parameters and natriuretic peptide levels were evaluated in cardiac
      hypertrophy produced by sequentially applied renovascular (RV) and
      deoxycorticosterone acetate-salt (DS) models of hypertension. We studied
      hypertensive rats by RV or DS treatment at 2 and 4 wk, as well as by the
      combination of 2 wk of each treatment in an inverse sequence: RV 2 wk/DS 2 wk
      (RV2/DS2) and DS 2 wk/RV 2 wk (DS2/RV2). The in vivo cardiac function,
      interstitial fibrosis, and synthesis and secretion of types A (ANP) and B (BNP)
      natriuretic peptides were monitored in hypertensive models compared with their
      corresponding sham (Sh2, Sh4). There were no differences in relaxation parameters
      among RV or DS groups and combined treatments. Left ventricular +dP/dt(max)
      increased only in RV4 (P < 0.01 vs. Sh4), and this increase was abolished in
      RV2/DS2. Interstitial collagen concentration increased after 4 wk in both RV4 and
      RV2/DS2 groups. Although there were no changes in collagen concentration in
      either DS2 or DS4 groups, clipping after 2 wk of DS (DS2/RV2) remarkably
      stimulated interstitial fibrosis (P < 0.01 vs. DS2). Plasma BNP increased in RV
      treatment at 4 wk (P < 0.001 vs. Sh4), but not in DS. Interestingly, RV applied
      after the 2 wk of DS treatment induced a marked increase in BNP levels (P < 0.001
      vs. Sh4). In this regard, plasma BNP appears to be a reliable indicator of
      pressure overload. Our results suggest that the second stimulus of mechanical
      overload in combined models of hypertension determines the evolution of
      hypertrophy and synthesis and secretion of ANP and BNP.

PMID- 20139324
TI  - Intrinsic sex-specific differences in microvascular endothelial cell
      phosphodiesterases.
AB  - The importance of gonadal hormones in the regulation of vascular function has
      been documented. An alternate and essential contribution of the sex chromosomes
      to sex differences in vascular function is poorly understood. We reported
      previously sex differences in microvessel permeability (P(s)) responses to
      adenosine that were mediated by the cAMP signaling pathway (Wang J, PhD thesis,
      2005; Wang J and Huxley V, Proceedings of the VIII World Congress of
      Microcirculation, 2007; Wang J and Huxley VH, Am J Physiol Heart Circ Physiol
      291: H3094-H3105, 2006). The two cyclic nucleotides, cAMP and cGMP, central to
      the regulation of vascular barrier integrity, are hydrolyzed by
      phosphodiesterases (PDE). We hypothesized that microvascular endothelial cells
      (EC) would retain intrinsic and inheritable sexually dimorphic genes with respect
      to the PDEs modulating EC barrier function. Primary cultured microvascular EC
      from skeletal muscles isolated from male and female rats, respectively, were
      used. SRY (a sex-determining region Y gene) mRNA expression was observed
      exclusively in male, not female, cells. The predominant isoform among PDE1-5,
      present in both XY and XX EC, was PDE4. Expression mRNA levels of PDE1A (male >
      female) and PDE3B (male < female) were sex dependent; PDE2A, PDE4D, and PDE5A
      were sex independent. Barrier function, P(s), was determined from measures of
      albumin flux across confluent primary cultured microvessel XY and XX EC
      monolayers. Consistent with intact in situ microvessels, basal monolayer P(s) did
      not differ between XY (1.7 +/- 0.2 x 10(-6) cm/s; n = 8) and XX (1.8 +/- 0.1 x
      10(-6) cm/s; n = 10) EC. Cilostazol, a PDE3 inhibitor, reduced (11%, P < 0.05)
      P(s) in XX, not XY, cells. These findings demonstrate the presence and
      maintenance of intrinsic sex-related differences in gene expression and cellular
      phenotype by microvascular EC in a gonadal-hormone-free environment. Furthermore,
      intrinsic cell-sex likely contributes significantly to sexual dimorphism in
      cardiovascular function.

PMID- 20139325
TI  - Expression of sensory neuropeptides in tendon is associated with failed healing
      and activity-related tendon pain in collagenase-induced tendon injury.
AB  - BACKGROUND: Increase in expression of substance P (SP) and calcitonin gene
      related peptide (CGRP) has been reported in clinical samples of tendinopathy.
      PURPOSE: To examine the spatial-temporal expression of these neuropeptides as
      well as their association with activity-related tendon pain, matrix degeneration,
      failed healing, and pathologic calcification in an established collagenase
      induced tendon injury rat model. STUDY DESIGN: Controlled laboratory study.
      METHODS: Collagenase or saline was injected into the patellar tendon of rats. At
      weeks 2, 4, 8, 12, and 16, just before the rats were sacrificed, the double
      stance duration of rats was examined by gait analysis method. After sacrifice,
      the patellar tendons were harvested for histologic analysis and
      immunohistochemical staining of SP and CGRP. RESULTS: There was an increase of SP
      and CGRP immunopositivity in tendon fibroblasts at week 2. The immunopositive
      signals decreased at weeks 4 and 8 and were observed in chondrocyte-like cells.
      At weeks 12 and 16, the immunopositive staining increased again and was observed
      in cells embedded in calcific deposits in addition to tendon fibroblasts and
      chondrocyte-like cells. The expression pattern was consistent with matrix
      degeneration, calcification, and failed healing in the animal model. There were
      significant positive correlations of immunopositivity of SP (rho = .502, P =
      .002) and CGRP (rho = .483, P = .003) with double-stance duration after
      collagenase injection. CONCLUSION: There was increased expression of SP and CGRP
      after collagenase-induced tendon injury, and their expression was positively
      associated with double-stance duration. Clinical Relevance Substance P and CGRP
      might be involved in the pathogenesis and origin of pain of tendinopathy and
      could be the targets for future intervention.

PMID- 20139326
TI  - Treatment of the unstable ankle with an osteochondral lesion: results and long
      term follow-up.
AB  - BACKGROUND: Few reports have studied the treatment of osteochondral lesions of
      the talus (OLTs) in the setting of lateral ankle instability. HYPOTHESIS:
      Arthroscopic treatment of an OLT and lateral ankle stabilization in the same
      sitting is safe and leads to reliable improvement of symptoms. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Of 37 patients who underwent concomitant
      treatment of an OLT and lateral ankle stabilization, 31 (84%) were evaluated at a
      mean of 7.3 years postoperatively. Patients were evaluated by physical
      examination, the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot
      Scale, the modified Weber Scale, the Single Assessment Numeric Evaluation, the
      Berndt and Harty Scale, and the Medical Outcomes Study 36-Item Short-Form Health
      Survey. RESULTS: The average postoperative ankle-hindfoot score was 89, the mean
      modified Weber score was 85, and the mean Single Assessment Numeric Evaluation
      was 86. In sum, 74% of patients had a good result on the Berndt and Harty Scale,
      23% had a fair result, and 3% had a poor result. Of the short-form survey, the
      mean physical function score was 86.5, and the mean summary physical component
      score was 52.3. For the 13 patients for whom prospective ankle-hindfoot scores
      were available, a statistically significant improvement was seen, from 75 points
      preoperatively to 91 points postoperatively (P <.001). CONCLUSION: Simultaneous
      arthroscopic treatment of an OLT and open lateral ankle stabilization is a safe
      and effective procedure. The presence of an osteochondral lesion had a negative
      effect on the overall result when compared to that of patients who underwent
      lateral ankle stabilization as an isolated procedure.

PMID- 20139327
TI  - Chronic ankle instability alters central organization of movement.
AB  - BACKGROUND: Chronic ankle instability alters spinal level sensorimotor function
      and is hypothesized to alter supraspinal motor control mechanisms. Gait
      initiation is a functional task modulated by supraspinal pathways, but the effect
      of chronic ankle instability, a peripheral musculoskeletal impairment, on gait
      initiation and thus supraspinal motor control mechanisms remains unknown.
      PURPOSE: This study was conducted to determine if supraspinal aspects of motor
      control are altered in subjects with chronic ankle instability. STUDY DESIGN:
      Controlled laboratory study. METHODS: Subjects with chronic ankle instability (5
      males, 15 females; age, 20.5 +/- 1.0 years; height, 169.8 +/- 9.8 cm; weight,
      74.2 +/- 20.2 kg) and uninjured controls (4 males, 16 females; age, 20.85 +/- 1.6
      years; height, 164.3 +/- 7.9 cm; weight, 64.2 +/- 10.62 kg) completed 5 gait
      initiation trials for each leg at a self-selected pace. The resulting trajectory
      of the center of pressure trace was investigated and peak center of pressure
      excursions in the anteroposterior and mediolateral directions, peak resultant
      center of pressure excursions, and average direction-specific velocities were
      calculated. RESULTS: Significant group x limb interactions were noted during the
      first (resultant center of pressure displacement [F(1,37) = 4.60, P = .04]) and
      second (mediolateral center of pressure displacement [F(1,37) = 3.82, P = .05])
      period of gait initiation. Center of pressure displacement was reduced (impaired)
      in the involved limb of the chronic ankle instability group (resultant, 0.29 +/-
      0.02; mediolateral, 0.72 +/- 0.02) relative to the uninvolved limb of the chronic
      ankle instability group (resultant, 0.32 +/- 0.02; mediolateral, 0.76 +/- 0.02)
      and both limbs of the control group (resultant, 0.32 +/- 0.02; mediolateral, 0.74
      +/- 0.02) when the involved limb of the chronic ankle instability group served as
      the initial stance limb. CONCLUSION: These interactions suggest that supraspinal
      motor control mechanisms are altered in subjects with chronic ankle instability
      to place a greater emphasis on reducing the postural demands on the involved
      limb. CLINICAL RELEVANCE: These changes suggest that supraspinal adaptations to
      motor control may be an important contributor to the underlying neurophysiologic
      mechanism of chronic ankle instability. The presence of supraspinal adaptations
      in subjects with chronic ankle instability also indicates that health care
      providers and rehabilitation specialists treat chronic ankle instability as a
      global/central and not just a local/peripheral injury.

PMID- 20139328
TI  - Epidemiology of weight training-related injuries presenting to United States
      emergency departments, 1990 to 2007.
AB  - BACKGROUND: As participation in weight training in the United States increases,
      the number of persons at injury risk increases. PURPOSE: To examine weight
      training-related injuries in patients presenting to US emergency departments from
      1990 to 2007. Study Design Descriptive epidemiology study. METHODS: Weight
      training-related injury data were analyzed from the US Consumer Product Safety
      Commission's National Electronic Injury Surveillance System. Sample weights
      provided by this organization calculated national estimates of weight training
      related injuries from the 100-hospital sample. RESULTS: From 1990 to 2007, 25 335
      weight training injuries were seen in US emergency departments, correlating to an
      estimated 970 801 injuries nationwide. Patients' mean age was 27.6 years (range,
      6-100 years); 82.3% were male. The upper trunk (25.3%) and lower trunk (19.7%)
      were the most commonly injured body parts. The most common diagnosis was
      sprain/strain (46.1%). The most common mechanism of injury was weights dropping
      on the person (65.5%). A large number of injuries occurred with free weights
      (90.4%). Males had a larger proportion of upper trunk injuries (26.8%; injury
      proportion ratio [IPR], 1.45; 95% confidence interval [CI]: 1.36-1.57; P <.001)
      than females (18.4%). Females had a larger proportion of foot injuries (22.9%;
      IPR, 2.09; 95% CI: 1.93-2.26; P <.001) than males (11.0%). Persons 12 years and
      younger had a larger proportion of hand (37.9%; IPR, 2.08; 95% CI: 1.76-2.46; P
      <.001) injuries than persons 13 years or older (18.2%). Persons 55 years and
      older were injured more when using machines (18.2%; IPR, 1.96; 95% CI: 1.47-2.61,
      P <.001) than persons 54 years and younger (9.3%). Persons using free weights
      sustained a greater proportion of fractures/dislocations (23.6%; IPR, 2.44; 95%
      CI: 1.92-3.09; P <.001) than persons using machines (9.7%). CONCLUSION: Further
      research is needed to drive development of targeted, age- and gender-specific,
      evidence-based injury prevention strategies to decrease injury rates among weight
      training participants.

PMID- 20139329
TI  - Effects of fatigue due to contraction of evertor muscles on the ankle joint
      position sense in male soccer players.
AB  - BACKGROUND: The high incidence of ankle sprains that occur later in matches
      suggests that fatigue may contribute to altered neuromuscular control of the
      ankle. Moreover, deficits in ankle joint position sense (JPS) were seen in
      patients with a history of recurrent ankle sprains. It has been hypothesized that
      ankle sprains may be related to altered ankle JPS as a consequence of fatigue.
      PURPOSE: To evaluate if fatiguing contractions of evertor muscles alter the ankle
      JPS. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty-six soccer
      players (age, 24.7 +/- 1.3 years; height, 183.7 +/- 8.2 cm; weight, 78.9 +/- 7.9
      kg) were recruited. Subjects were asked to recognize 2 positions (15 degrees of
      inversion and maximal active inversion minus 5 degrees ) for 2 conditions: normal
      and fatigue. Muscular fatigue was induced in evertor muscles of the dominant leg
      by using isometric contractions. The average of the absolute and variable errors
      of 3 trials were recorded for both fatigue and nonfatigue conditions. A matched
      control group of 36 soccer players (age, 23.9 +/- 0.9 years; height, 181.2 +/-
      6.9 cm; weight, 77.8 +/- 6.5 kg) was asked to recognize the same positions,
      before a soccer match and after 45 minutes of playing, and their same scores were
      recorded. Finally, results of the 2 groups were compared. RESULTS: There was
      significant decrease in subjects' ability to recognize passive and active
      repositioning of their ankle after a fatigue protocol (P <.001). Passive and
      active JPS were reduced after playing (P <.001). There was no significant
      difference between 2 groups in the results of JPS before and after the
      intervention (P > .1). CONCLUSION: The acuity of the ankle JPS is reduced
      subsequent to a fatigue protocol and after a soccer match. CLINICAL RELEVANCE:
      Evaluation of athletes' ankle JPS before returning to physical activity may
      prevent further injuries.

PMID- 20139330
TI  - Implantation of autogenous meniscal fragments wrapped with a fascia sheath
      enhances fibrocartilage regeneration in vivo in a large harvest site defect.
AB  - BACKGROUND: Concerning meniscal tissue regeneration, many investigators have
      studied the development of a tissue-engineered meniscus. However, the utility
      still remains unknown. HYPOTHESIS: Implantation of autogenous meniscal fragments
      wrapped with a fascia sheath into the donor site meniscal defect may
      significantly enhance fibrocartilage regeneration in vivo in the defect. STUDY
      DESIGN: Controlled laboratory study. METHODS: Seventy-five mature rabbits were
      used in this study. In each animal, an anterior one-third of the right medial
      meniscus was resected. Then, the animals were divided into the following 3 groups
      of 25 rabbits each: In group 1, no treatment was applied to the meniscal defect.
      In group 2, the defect was covered with a fascia sheath. In group 3, after the
      resected meniscus was fragmented into small pieces, the fragments were grafted
      into the defect. Then, the defect with the meniscal fragments was covered with a
      fascia sheath. In each group, 5 rabbits were used for histological evaluation at
      3, 6, and 12 weeks after surgery, and 5 rabbits were used for biomechanical
      evaluation at 6 and 12 weeks after surgery. RESULTS: Histologically, large round
      cells in group 3 were scattered in the core portion of the meniscus-shaped
      tissue, and the matrix around these cells was positively stained by safranin O
      and toluisin blue at 12 weeks. The histological score of group 3 was
      significantly higher than that of group 1 and group 2. Biomechanically, the
      maximal load and stiffness of group 3 were significantly greater than those of
      groups 1 and 2. CONCLUSION: This study clearly demonstrated that implantation of
      autogenous meniscal fragments wrapped with a fascia sheath into the donor site
      meniscal defect significantly enhanced fibrocartilage regeneration in vivo in the
      defect at 12 weeks after implantation in the rabbit. CLINICAL RELEVANCE: This
      study proposed a novel strategy to treat a large defect after a meniscectomy.

PMID- 20139331
TI  - Combined flexor-pronator mass and ulnar collateral ligament injuries in the
      elbows of older baseball players.
AB  - BACKGROUND: Ulnar collateral ligament reconstruction techniques have afforded
      baseball players up to a reported 90% return to prior or higher level of play. A
      subpopulation exists with less impressive clinical outcomes potentially related
      to the presence of a concomitant flexor-pronator mass injury. HYPOTHESIS/PURPOSE:
      Combined flexor-pronator and ulnar collateral ligament injuries occur in older
      players, and results in this group are inferior to those reported for isolated
      ulnar collateral ligament reconstructions. STUDY DESIGN: Case Series; Level of
      evidence, 4. METHODS: All baseball players who had ulnar collateral ligament
      reconstructions by 1 surgeon over a 6-year period were identified, and the
      authors studied those treated for a combined flexor-pronator and ulnar collateral
      ligament injury. The ulnar collateral ligament reconstruction was accomplished
      using the docking technique, and the flexor-pronator injury was treated with
      debridement if tendinotic or reattachment if torn. A 2-sample t test was
      conducted to evaluate the likelihood of developing the combined flexor
      pronator/ulnar collateral ligament compared with ulnar collateral ligament injury
      based on age, while a Pearson chi(2) test was used to evaluate the likelihood of
      a patient being > or =30 years of age in the combined flexor-pronator/ulnar
      collateral ligament versus ulnar collateral ligament groups. Outcome was assessed
      using a modified Conway classification. RESULTS: A total of 187 male baseball
      players between 14 and 42 years of age (mean, 20.7 years) had an ulnar collateral
      ligament reconstruction by 1 surgeon. Eight (4%) of 187 baseball players were
      treated for the combined flexor-pronator/ulnar collateral ligament injury. There
      was a statistically significant difference in age between the ulnar collateral
      ligament group (20.1 years) and the flexor-pronator/ulnar collateral ligament
      group (33.4 years) (P < .001). Age > or =30 years was a statistically significant
      age limit to predict the presence of a combined flexor-pronator/ulnar collateral
      ligament injury (88%) compared with an isolated ulnar collateral ligament injury
      (1%) (P < .001). Outcomes were 1 excellent (12.5%), 2 fair (25%), and 5 poor
      (62.5%). Conclusion Combined fflexor-pronator and ulnar collateral ligament
      injuries in baseball players may portend a worse prognosis, with a 12.5% return
      to prior level of play. Older age (> or =30 years) is a risk factor in the
      development of this combined injury. When combined flexor-pronator/ulnar
      collateral ligament injury is suspected preoperatively, patients should be
      counseled on expected outcomes appropriately.

PMID- 20139332
TI  - Single-tunnel double-bundle anterior cruciate ligament reconstruction with
      anatomical placement of hamstring tendon graft: can it restore normal knee joint
      kinematics?
AB  - BACKGROUND: Anatomical reconstruction techniques that can restore normal joint
      kinematics without increasing surgical complications could potentially improve
      clinical outcomes and help manage anterior cruciate ligament injuries more
      efficiently. HYPOTHESIS: Single-tunnel double-bundle anterior cruciate ligament
      reconstruction with anatomical placement of hamstring tendon graft can more
      closely restore normal knee anterior-posterior, medial-lateral, and internal
      external kinematics than can conventional single-bundle anterior cruciate
      ligament reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS:
      Kinematic responses after single-bundle anterior cruciate ligament reconstruction
      and single-tunnel double-bundle anterior cruciate ligament reconstruction with
      anatomical placement of hamstring tendon graft were compared with the intact knee
      in 9 fresh-frozen human cadaveric knee specimens using a robotic testing system.
      Kinematics of each knee were determined under an anterior tibial load (134 N), a
      simulated quadriceps load (400 N), and combined torques (10 N.m valgus and 5 N.m
      internal tibial torques) at 0 degrees , 15 degrees , 30 degrees , 60 degrees ,
      and 90 degrees of flexion. RESULTS: Anterior tibial translations were more
      closely restored to the intact knee level after single-tunnel double-bundle
      reconstruction with anatomical placement of hamstring tendon graft than with a
      single-bundle reconstruction under the 3 external loading conditions. Under
      simulated quadriceps load, the mean internal tibial rotations after both
      reconstructions were lower than that of the anterior cruciate ligament-intact
      knee with no significant differences between these 3 knee conditions at 0 degrees
      and 30 degrees of flexion (P > .05). The increased medial tibial shifts of the
      anterior cruciate ligament-deficient knees were restored to the intact level by
      both reconstruction techniques under the 3 external loading conditions.
      CONCLUSION: Single-tunnel double-bundle anterior cruciate ligament reconstruction
      with anatomical placement of hamstring tendon graft can better restore the
      anterior knee stability compared with a conventional single-bundle
      reconstruction. Both reconstruction techniques are efficient in restoring the
      normal medial-lateral stability but overcorrect the internal tibial rotations.
      CLINICAL RELEVANCE: Single-tunnel double-bundle anterior cruciate ligament
      reconstruction with anatomical placement of hamstring tendon graft could provide
      improved clinical outcomes over a conventional single-bundle reconstruction.

PMID- 20139333
TI  - Tunnel position and relationship to postoperative knee laxity after double-bundle
      anterior cruciate ligament reconstruction with a transtibial technique.
AB  - BACKGROUND: Several laboratory studies have pointed out a potential risk of
      femoral tunnel misplacement in anterior cruciate ligament reconstruction with a
      transtibial technique. The tunnel malposition away from the anatomic attachment
      may result in increased postoperative knee laxity in double-bundle
      reconstruction. PURPOSE: This study was conducted to evaluate the femoral and
      tibial tunnel positions in transtibial double-bundle reconstruction, and to
      determine the relationship between the tunnel positions and the results of the
      postoperative knee laxity examinations. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Fifty-three of 71 patients who underwent transtibial double
      bundle reconstruction from 2004 to 2005 were followed more than 24 months. The
      tunnel positions for the anteromedial and posterolateral grafts were measured
      using 3-dimensional computed tomography images applying the quadrant method. The
      postoperative knee laxity was examined with the KT-1000 arthrometer manual
      maximum test, anterior drawer test, and pivot-shift test. RESULTS: The deep
      shallow position (parallel to Blumensaat's line) and high-low position
      (perpendicular to Blumensaat's line) of the femoral tunnels were 27.7% +/- 5.6%
      from the most posterior condylar contour and 16.3% +/- 5.2% from Blumensaat's
      line for the anteromedial graft, and 35.5% +/- 6.4% and 48.0% +/- 5.4% for the
      posterolateral graft. The medial-lateral and anterior-posterior positions of the
      tibial tunnels were 46.1% +/- 2.6% from the most medial contour and 36.5% +/-
      4.9% from the most anterior contour for the anteromedial graft, and 47.5% +/-
      3.1% and 51.6% +/- 5.0% for the posterolateral graft. There was no statistical
      correlation between any parameters of the femoral or tibial tunnel position and
      the results of the knee laxity tests. CONCLUSION: The femoral tunnels placed in
      transtibial double-bundle reconstruction were located appropriately in high-low
      and deep-shallow orientation, but had larger variability than the previously
      reported data of the anatomic femoral attachment. However, the variability of the
      femoral tunnel position was not so large as to result in graft insufficiency with
      increased postoperative knee laxity.

PMID- 20139334
TI  - Cerebral localization of functions and the neurology of language: fact versus
      fiction or is it something else?
AB  - Over the last 15 years there has been a burgeoning number of publications using
      functional brain imaging (>40,000 articles based on an ISI/Web of Science search)
      to localize behavioral and cognitive processes to specific areas in the human
      brain that are often not confirmed by traditional, lesion-based studies. Thus,
      there is a need to reassess what cerebral localization of functions is and is
      not. Otherwise, there is no rational way to interpret the escalating claims of
      localization in the functional imaging literature that is taking on the
      appearance of neurophysiologic "phrenology". This article will present arguments
      to suggest that functional localization in the brain is a robust but very
      dynamic, four-dimensional process. It is a learned phenomenon driven over time by
      large-scale, spatially distributed, neural networks seeking to efficiently
      maximize the processing, storage, and manipulation of information for cognitive
      and behavioral operations. Because of historical considerations and space
      limitations, the main focus will be on localization of language-related functions
      whose theoretical neurological basis can be generalized for any complex cognitive
      behavioral function.

PMID- 20139335
TI  - FSH aggravates periodontitis-related bone loss in ovariectomized rats.
AB  - Alveolar bone loss is one of the prominent pathologic and clinical features of
      periodontitis. Recently, the direct effect of follicle-stimulating hormone (FSH)
      on bone resorption has been demonstrated. However, the effect of FSH on alveolar
      bone loss remains unknown. This study tested the hypothesis that FSH would
      exacerbate periodontitis-related alveolar bone loss. Experimental periodontitis
      was induced in ovariectomized rats, and the rats were treated with extrinsic FSH
      or its inhibitor, leuprorelin. After mandibles were collected, we performed
      morphological examinations to evaluate bone loss, enzyme histochemical tests for
      osteoclasts, and immunohistochemical examinations for FSH receptor (FSHR). The
      results showed that FSH significantly increased alveolar bone resorption compared
      with non-FSH-treated ovariectomized rats (P < 0.05), and the number of FSHR
      positive cells was positively correlated with alveolar bone loss area (r = 0.682,
      P < 0.01). Our results suggested that FSH can aggravate alveolar bone loss by
      FSHR, independent of estrogen.

PMID- 20139336
TI  - Factors affecting wound healing.
AB  - Wound healing, as a normal biological process in the human body, is achieved
      through four precisely and highly programmed phases: hemostasis, inflammation,
      proliferation, and remodeling. For a wound to heal successfully, all four phases
      must occur in the proper sequence and time frame. Many factors can interfere with
      one or more phases of this process, thus causing improper or impaired wound
      healing. This article reviews the recent literature on the most significant
      factors that affect cutaneous wound healing and the potential cellular and/or
      molecular mechanisms involved. The factors discussed include oxygenation,
      infection, age and sex hormones, stress, diabetes, obesity, medications,
      alcoholism, smoking, and nutrition. A better understanding of the influence of
      these factors on repair may lead to therapeutics that improve wound healing and
      resolve impaired wounds.

PMID- 20139337
TI  - Tooth loss, apolipoprotein E, and decline in delayed word recall.
AB  - Our previous research suggests an association between a low number of teeth and
      increased risk of dementia. The aim of the present study was to determine if a
      low number of teeth is specifically related to memory decline as evidenced by low
      Delayed Word Recall scores. In addition, we examined the combined effect of a low
      number of teeth and the apolipoprotein E epsilon4 allele on Delayed Word Recall
      scores. We hypothesized that the scores of those who had the allele and a low
      number of teeth (0-9) would decline more rapidly over time than those
      participants with a greater number of teeth who lacked the allele. We found that
      individuals with both risk factors (the allele and fewer teeth) had lower Delayed
      Word Recall scores at the first examination and declined more quickly compared
      with participants with neither of these risk factors or with either risk factor
      alone.

PMID- 20139338
TI  - Anxiety and quality of life in phobic dental patients.
AB  - Little is known about the anxiety patients experience before attending for dental
      treatment. The aim of this study was to determine, in dentally phobic patients,
      the temporal relationship of pre-operative anxiety levels, and the disruption to
      daily life caused by this. Twenty-four phobic and 19 comparison (non-phobic)
      dental patients were recruited. Four validated questionnaires were used to assess
      anxiety and quality of life, which each patient completed for 5 days prior to,
      and on the day of, treatment. Those in the experimental group were found to have
      significantly greater levels of dental and general anxiety, and a significantly
      lower quality of life compared with those in the comparison group. Significant
      temporal relationships were found with all of the questionnaires. Dental and
      general anxiety scores were significantly correlated with quality-of-life
      measures. This study suggests that phobic dental patients are experiencing
      significant increased anxiety, and significant negative quality-of-life effects,
      in this period.

PMID- 20139340
TI  - In vivo dentin remineralization by calcium-phosphate cement.
AB  - Minimally invasive caries-removal procedures remove only caries-infected dentin
      and preserve caries-affected dentin that becomes remineralized. Dental cements
      containing calcium phosphate promote remineralization. This study evaluated the
      in vivo remineralization capacity of resin-based calcium-phosphate cement (Ca-P)
      used for indirect pulp-capping. Carious and sound teeth indicated for extraction
      were randomly restored with the Ca-P base or without base (control), followed by
      adhesive restoration. Study teeth were extracted after three months, followed by
      elemental analysis of the cavity floor. Mineral content of affected or sound
      dentin at the cavity floor was quantified by electron probe micro-analysis to 100
      mum depth. After three months, caries-affected dentin underneath the Ca-P base
      showed significantly increased calcium and phosphorus content to a depth of 30
      mum. Mineral content of treated caries-affected dentin was in the range of
      healthy dentin, revealing the capacity of Ca-P base to promote remineralization
      of caries-affected dentin.

PMID- 20139339
TI  - Biofilm dispersal: mechanisms, clinical implications, and potential therapeutic
      uses.
AB  - Like all sessile organisms, surface-attached communities of bacteria known as
      biofilms must release and disperse cells into the environment to colonize new
      sites. For many pathogenic bacteria, biofilm dispersal plays an important role in
      the transmission of bacteria from environmental reservoirs to human hosts, in
      horizontal and vertical cross-host transmission, and in the exacerbation and
      spread of infection within a host. The molecular mechanisms of bacterial biofilm
      dispersal are only beginning to be elucidated. Biofilm dispersal is a promising
      area of research that may lead to the development of novel agents that inhibit
      biofilm formation or promote biofilm cell detachment. Such agents may be useful
      for the prevention and treatment of biofilms in a variety of industrial and
      clinical settings. This review describes the current status of research on
      biofilm dispersal, with an emphasis on studies aimed to characterize dispersal
      mechanisms, and to identify environmental cues and inter- and intracellular
      signals that regulate the dispersal process. The clinical implications of biofilm
      dispersal and the potential therapeutic applications of some of the most recent
      findings will also be discussed.

PMID- 20139341
TI  - Lack of serotype antigen in A. actinomycetemcomitans.
AB  - Aggregatibacter actinomycetemcomitans is divided into 6 serotypes. Occurrence of
      non-serotypeable strains is known, but background reasons are unclear. We
      hypothesized that non-serotypeable strains represent new serotypes or have
      altered expression of serotype-specific polysaccharide antigen (S-PA). We first
      characterized 311 strains from 189 individuals using both immunoassay- and PCR
      based serotyping. Next, using natural human infection and rabbit immunization
      approaches, we clarified whether the phenotypically non-serotypeable strains
      expressed S-PA. Immunoassay identified serotypes a-f among 216 strains from 159
      individuals. The remaining 95 strains from 30 individuals were phenotypically non
      serotypeable. Yet, all these strains were identified by PCR-typing as serotype a
      , b-, c-, or f. Non-serotypeability was confirmed by Western immunoblot with
      respective rabbit antisera. Patient sera remained non-reactive with autologous
      non-serotypeable strains at the serotype-specific region. Rabbit immunization
      with a phenotypically non-serotypeable strain induced no antibody production
      against S-PA. Thus, phenotypically non-serotypeable strains did not include novel
      serotypes, but lacked S-PA expression.

PMID- 20139342
TI  - Alpha2-adrenoceptors coordinate swallowing and respiration.
AB  - Because the discoordination between swallowing and respiration may cause severe
      respiratory disorders such as aspiration pneumonia, understanding the neuronal
      mechanisms underlying such coordination is important. Recently, it was reported
      that medullary noradrenergic neurons are involved in evoking esophageal-gastric
      relaxation reflex, leading to a hypothesis that such neurons are also involved in
      swallowing-respiration coordination. We tested this hypothesis using an in vitro
      brain-stem preparation obtained from neonatal rats. A temporal inhibition of
      respiratory rhythm was consistently observed when swallowing activity was induced
      by electrical stimulations to the supralaryngeal nerve. We found that a broad
      adrenergic receptor agonist, norepinephrine, markedly blocked the swallowing
      induced temporal inhibition of respiration. Further studies revealed that
      swallowing-induced respiratory inhibition is blocked by an alpha2-adrenergic
      receptor agonist and enhanced by an alpha2-adrenergic receptor antagonist,
      indicating an important role of alpha2-adrenergic receptors in regulation of the
      coordination between swallowing and respiration in vitro.

PMID- 20139343
TI  - Ume6 is required for the MATa/MATalpha cellular identity and transcriptional
      silencing in Kluyveromyces lactis.
AB  - To explore the similarities and differences of regulatory circuits among budding
      yeasts, we characterized the role of the unscheduled meiotic gene expression 6
      (UME6) gene in Kluyveromyces lactis. We found that Ume6 was required for
      transcriptional silencing of the cryptic mating-type loci HMLalpha and HMRa.
      Chromatin immunoprecipitation (ChIP) suggested that Ume6 acted directly by
      binding the cis-regulatory silencers of these loci. Unexpectedly, a MATa ume6
      strain was mating proficient, whereas a MATalpha ume6 strain was sterile. This
      observation was explained by the fact that ume6 derepressed HMLalpha2 only
      weakly, but derepressed HMRa1 strongly. Consistently, two a/alpha-repressed genes
      (MTS1 and STE4) were repressed in the MATalpha ume6 strain, but were expressed in
      the MATa ume6 strain. Surprisingly, ume6 partially suppressed the mating defect
      of a MATa sir2 strain. MTS1 and STE4 were repressed in the MATa sir2 ume6 double
      mutant strain, indicating that the suppression acted downstream of the a1/alpha2
      repressor. We show that both STE12 and the MATa2/HMRa2 genes were overexpressed
      in the MATa sir2 ume6 strain. Consistent with the idea that this deregulation
      suppressed the mating defect, ectopic overexpression of Ste12 and a2 in a MATa
      sir2 strain resulted in efficient mating. In addition, Ume6 served as a block to
      polyploidy, since ume6/ume6 diploids mated as pseudo a-strains. Finally, Ume6 was
      required for repression of three meiotic genes, independently of the Rpd3 and
      Sin3 corepressors.

PMID- 20139344
TI  - Alterations in DNA replication and histone levels promote histone gene
      amplification in Saccharomyces cerevisiae.
AB  - Gene amplification, a process that increases the copy number of a gene or a
      genomic region to two or more, is utilized by many organisms in response to
      environmental stress or decreased levels of a gene product. Our previous studies
      in Saccharomyces cerevisiae identified the amplification of a histone H2A-H2B
      gene pair, HTA2-HTB2, in response to the deletion of the other H2A-H2B gene pair,
      HTA1-HTB1. This amplification arises from a recombination event between two
      flanking Ty1 elements to form a new, stable circular chromosome and occurs at a
      frequency higher than has been observed for other Ty1-Ty1 recombination events.
      To understand the regulation of this amplification event, we screened the S.
      cerevisiae nonessential deletion set for mutations that alter the amplification
      frequency. Among the deletions that increase HTA2-HTB2 amplification frequency,
      we identified those that either decrease DNA replication fork progression
      (rrm3Delta, dpb3Delta, dpb4Delta, and clb5Delta) or that reduce histone H3-H4
      levels (hht2-hhf2Delta). These two classes are related because reduced histone H3
      H4 levels increase replication fork pauses, and impaired replication forks cause
      a reduction in histone levels. Consistent with our mutant screen, we found that
      the introduction of DNA replication stress by hydroxyurea induces the HTA2-HTB2
      amplification event. Taken together, our results suggest that either reduced
      histone levels or slowed replication forks stimulate the HTA2-HTB2 amplification
      event, contributing to the restoration of normal chromatin structure.

PMID- 20139345
TI  - The role of advantageous mutations in enhancing the evolution of a recombination
      modifier.
AB  - Although the evolution of recombination is still a major problem in evolutionary
      genetics, recent theoretical studies have shown that recombination can evolve by
      breaking down interference ("Hill-Robertson effects") among multiple loci. This
      leads to selection on a recombination modifier in a population subject to
      recurrent deleterious mutation. Here, we use computer simulations to investigate
      the evolution of a recombination modifier under three different scenarios of
      recurrent mutation in a finite population: (1) mutations are deleterious only,
      (2) mutations are advantageous only, and (3) there is a mixture of deleterious
      and advantageous mutations. We also investigate how linkage disequilibrium, the
      strength of selection acting on a modifier, and effective population size change
      under the different scenarios. We observe that adding even a small number of
      advantageous mutations increases the fixation rate of modifiers that increase
      recombination, especially if the effects of deleterious mutations are weak.
      However, the strength of selection on a modifier is less than the summed
      strengths had there been deleterious mutations only and advantageous mutations
      only.

PMID- 20139346
TI  - Evaluating the impact of intimate partner violence on the perpetrator: the
      Perceived Consequences of Domestic Violence Questionnaire.
AB  - Surprisingly, little is known about how IPV perpetrators perceive the conse
      quences of their violent behavior. This article describes the development and
      evaluation of the Perceived Consequences of Domestic Violence Questionnaire
      (PCDVQ). The PCDVQ is a 27 item self report instrument designed to assess the
      consequences of intimate partner violence (IPV) as perceived by the perpetrator.
      Data from 124 nontreatment seeking, male, IPV perpetrators recruited from the
      community provided support for the internal consistency of the PCDVQ.
      Participants reported an average of 9.97 (SD = 4.57) consequences. Scores on the
      PCDVQ significantly predicted motivation for change, beta =.19, t(113) = 2.03, p
      < .05, and treatment seeking, chi(2)(df = 1) = 10.79, p < .01, odds ratio = 1.27
      (95% CI: 1.10 1.46). Clinical implications of this instrument are discussed.

PMID- 20139347
TI  - Exploring the nature and reasons for sexual violence within marriage among young
      women in Nepal.
AB  - Sexual violence within marriage (SVWM) is a major public health and human right
      issue and yet remains a much neglected research area, especially in Nepal. An
      exploratory study using free listing, in-depth case histories and causal flow
      analysis was conducted among two major ethnic groups in Nepal. Descriptive data
      collected from free listing indicate that about half of the married women aged 15
      to 24 years reported ever experiencing SVWM. Data revealed that the underlying
      reasons for SVWM are complex and complicated due to the multiple forms and
      contexts in which it occurs. For many couples, multiple factors alongside, and
      within, their socioeconomic and cultural contexts contribute to the risk of
      experiencing SVWM. Major factors escalating the risk to SVWM include gender
      norms, economic dependence of women, poverty, alcohol consumption of husband,
      lack of knowledge, social stigma, and lack of supportive familial and social
      environment. Raising awareness about sexual violence is required for its
      prevention and for managing the consequences. Further research is required to
      identify the determinants, the effects of SVWM on sexual and reproductive health
      outcomes and to help programs develop the best strategies for dealing with SVWM
      among young couples.

PMID- 20139348
TI  - Shelter and service receipt for victims of domestic violence in Illinois.
AB  - There is little empirical research about the services victims of violence in
      shelters receive and when, yet such information would increase our understanding
      of their unmet service needs especially after they leave shelter. This article
      utilizes data from a randomly selected sample of individuals in shelter to
      examine their service trajectories. Results indicate that most individuals
      receive service while in shelter. Individual counseling is likely to continue
      after shelter, but group counseling, employment, and educational assistance tend
      to end once shelter is over. The policy and practice implications of these
      results are discussed.

PMID- 20139349
TI  - Neural crest cell origin and signals for intrinsic neurogenesis in the mammalian
      respiratory tract.
AB  - Our study investigates the innervation of the respiratory tract during mouse
      embryonic development, with a focus on the identification of cell origin and
      essential developmental signals for the resident, or intrinsic, neurons. Using
      lineage tracing, we show that these intrinsic neurons are exclusively derived
      from neural crest cells, and cluster to form ganglia that reside in the dorsal
      trachea and medial bronchi with diminishing frequency. Comparisons of intrinsic
      neurogenesis between wild-type, glial cell-derived neurotrophic factor (GDNF)(-/
      ), neurturin(-/-), and tyrosine kinase receptor Ret(-/-) embryos, in combination
      with lung organ cultures, identified that Ret signaling, redundantly activated by
      GDNF family members, is required for intrinsic neurogenesis in the trachea and
      primary bronchi. In contrast, Ret deficiency exerts no effect on the innervation
      of the rest of the respiratory tract, suggesting that innervation by neurons
      whose cell bodies are located outside of the lung (so-called extrinsic neurons)
      is independent of Ret signaling. Furthermore, although the trachea, the
      esophagus, and their intrinsic neurons share foregut endoderm and a neural crest
      cell origin, respectively, the signals required for their intrinsic neurogenesis
      are divergent. Together, our results not only establish the neural crest lineage
      of intrinsic neurons in the respiratory tract, but also identify regional
      differences in the abundance and developmental signals of intrinsic neurons along
      the respiratory tract and in the esophagus.

PMID- 20139350
TI  - Nitric oxide inhibits highly selective sodium channels and the Na+/K+-ATPase in
      H441 cells.
AB  - Nitric oxide (NO) is an important regulator of Na(+) reabsorption by pulmonary
      epithelial cells and therefore of alveolar fluid clearance. The mechanisms by
      which NO affects epithelial ion transport are poorly understood and vary from
      model to model. In this study, the effects of NO on sodium reabsorption by H441
      cell monolayers were studied in an Ussing chamber. Two NO donors, (Z)-1-[N-(3
      aminopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate and diethylammonium (Z)-1
      (N,N-diethylamino)diazen-1-ium-1,2-diolate, rapidly, reversibly, and dose
      dependently reduced amiloride-sensitive, short-circuit currents across H441 cell
      monolayers. This effect was neutralized by the NO scavenger hemoglobin and was
      not observed with inactive NO donors. The effects of NO were not blocked by 8
      bromoguanosine-3',5'-cyclic monophosphate or by soluble guanylate cyclase
      inhibitors (methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) and
      were therefore independent of soluble guanylate cyclase signaling. NO targeted
      apical, highly selective, amiloride-sensitive Na(+) channels in basolaterally
      permeabilized H441 cell monolayers. NO had no effect on the activity of the human
      epithelial sodium channel heterologously expressed in Xenopus oocytes. NO
      decreased Na(+)/K(+)-ATPase activity in apically permeabilized H441 cell
      monolayers. The inhibition of Na(+)/K(+)-ATPase activity by NO was reversed by
      mercury and was mimicked by N-ethylmaleimide, which are agents that reverse and
      mimic, respectively, the reaction of NO with thiol groups. Consistent with these
      data, S-NO groups were detected on the Na(+)/K(+)-ATPase alpha subunit in
      response to NO-donor application, using a biotin-switch approach coupled to a
      Western blot. These data demonstrate that, in the H441 cell model, NO impairs
      Na(+) reabsorption by interfering with the activity of highly selective Na(+)
      channels and the Na(+)/K(+)-ATPase.

PMID- 20139352
TI  - Authorship intricacies.

PMID- 20139351
TI  - Non-muscle myosin light chain kinase isoform is a viable molecular target in
      acute inflammatory lung injury.
AB  - Acute lung injury (ALI) and mechanical ventilator-induced lung injury (VILI),
      major causes of acute respiratory failure with elevated morbidity and mortality,
      are characterized by significant pulmonary inflammation and alveolar/vascular
      barrier dysfunction. Previous studies highlighted the role of the non-muscle
      myosin light chain kinase isoform (nmMLCK) as an essential element of the
      inflammatory response, with variants in the MYLK gene that contribute to ALI
      susceptibility. To define nmMLCK involvement further in acute inflammatory
      syndromes, we used two murine models of inflammatory lung injury, induced by
      either an intratracheal administration of lipopolysaccharide (LPS model) or
      mechanical ventilation with increased tidal volumes (the VILI model). Intravenous
      delivery of the membrane-permeant MLC kinase peptide inhibitor, PIK, produced a
      dose-dependent attenuation of both LPS-induced lung inflammation and VILI (~50%
      reductions in alveolar/vascular permeability and leukocyte influx). Intravenous
      injections of nmMLCK silencing RNA, either directly or as cargo within
      angiotensin-converting enzyme (ACE) antibody-conjugated liposomes (to target the
      pulmonary vasculature selectively), decreased nmMLCK lung expression (~70%
      reduction) and significantly attenuated LPS-induced and VILI-induced lung
      inflammation (~40% reduction in bronchoalveolar lavage protein). Compared with
      wild-type mice, nmMLCK knockout mice were significantly protected from VILI, with
      significant reductions in VILI-induced gene expression in biological pathways
      such as nrf2-mediated oxidative stress, coagulation, p53-signaling, leukocyte
      extravasation, and IL-6-signaling. These studies validate nmMLCK as an attractive
      target for ameliorating the adverse effects of dysregulated lung inflammation.

PMID- 20139353
TI  - Impact of personal relevance and contextualization on word-picture matching by
      people with aphasia.
AB  - PURPOSE: To determine the effect of personal relevance and contextualization of
      images on the preferences and word-picture matching accuracy of people with
      severe aphasia. METHOD: Eight adults with aphasia performed 2 experimental tasks
      to reveal their preferences and accuracy during word-picture matching. The
      researchers used 3 types of visual stimuli-personally relevant, contextualized
      photographs; non-personally relevant, contextualized photographs; and
      noncontextualized, iconic images-paired with 3 types of target words-labels of
      people or objects, actions, and socially relevant events-as the stimulus
      materials. RESULTS: Data analysis showed that participants (a) preferred using
      personally relevant, contextualized photographs rather than other types of
      photographs/images to represent target words and (b) performed more accurate word
      picture matching when presented with target words associated with personally
      relevant, contextualized photographs than target words associated with
      noncontextualized or nonpersonalized photographs/images. CONCLUSIONS: Clinically,
      the findings highlight the importance of using personally relevant,
      contextualized photographs rather than generic contextualized photographs or
      noncontextualized, iconic images to support the communication attempts of people
      with aphasia who cannot communicate effectively using natural speech alone.

PMID- 20139354
TI  - DVT: a new era in anticoagulant therapy.

PMID- 20139355
TI  - CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle cell
      growth and migration.
AB  - OBJECTIVE: CCN3 belongs to the CCN family, which constitutes multifunctional
      secreted proteins that act as matrix cellular regulators. We investigated the
      pathophysiological roles of CCN3 in the vessels. METHODS AND RESULTS: We examined
      the effects of CCN3 on the proliferation and migration of rat vascular smooth
      muscle cells (VSMC). CCN3 knockout mice were created, and vascular phenotypes and
      neointimal hyperplasia induced by photochemically induced thrombosis were
      investigated. CCN3 suppressed the VSMC proliferation induced by fetal bovine
      serum. The neutralizing antibody for transforming growth factor-beta did not
      affect the growth inhibitory effect of CCN3. Moreover, CCN3 enhanced the mRNA
      expression of cyclin-dependent kinase inhibitors, p21 and p15. Gamma secretase
      inhibitor, an inhibitor of Notch signaling, partially inhibited the enhanced
      expression of p21 induced by CCN3. CCN3 also inhibited the VSMC migration.
      Finally, the histopathologic evaluation of the arteries 21 days after the
      endothelial injury revealed a 6-fold enhancement of neointimal thickening in the
      null mice compared with the wild-type mice. CONCLUSIONS: CCN3 suppresses
      neointimal thickening through the inhibition of VSMC migration and proliferation.
      Our findings indicate the involvement of CCN3 in vascular homeostasis, especially
      on injury, and the potential usefulness of this molecule in the modulation of
      atherosclerotic vascular disease.

PMID- 20139356
TI  - Coagulation factor IXa as a target for treatment and prophylaxis of venous
      thromboembolism.
AB  - Venous thromboembolism remains a frequent cause of vascular death. Despite
      advances in anticoagulant drug development, unmet needs remain, including limited
      treatment options for patients with severe renal impairment and the inability to
      fully reverse the effects of anticoagulants approved or in late-stage
      development. Because coagulation factor IXa plays a pivotal role in tissue factor
      mediated thrombin generation, it represents an attractive target for
      anticoagulant development. This article discusses the rationale for factor IXa as
      an anticoagulant target and the potential role in venous thromboembolism
      prevention or management of the 2 factor IXa inhibitors that have undergone
      testing in phase 1 or 2 trials: TTP889, an oral, small-molecule compound, and
      RB006, an aptamer-based compound, the intravenous and subcutaneous formulations
      of which are the anticoagulant components of the REG1 and REG2 anticoagulation
      systems, respectively.

PMID- 20139357
TI  - Rivaroxaban: a new oral factor Xa inhibitor.
AB  - Rivaroxaban is a direct inhibitor of factor Xa, a coagulation factor at a
      critical juncture in the blood coagulation pathway leading to thrombin generation
      and clot formation. It is selective for human factor Xa, for which it has >10 000
      fold greater selectivity than for other biologically relevant serine proteases
      (half-maximal inhibitory concentration [IC(50)], >20 micromol/L). Rivaroxaban
      inhibits factor Xa in a concentration-dependent manner (inhibitory constant
      [K(i)], 0.4 nmol/L) and binds rapidly (kinetic association rate constant [k(on)],
      1.7x10(7) mol/L(-1) s(-1)) and reversibly (kinetic dissociation rate constant
      [k(off)], 5x10(-3) s(-1)). By inhibiting prothrombinase complex-bound (IC(50),
      2.1 nmol/L) and clot-associated factor Xa (IC(50), 75 nmol/L), rivaroxaban
      reduces the thrombin burst during the propagation phase. In animal models of
      venous and arterial thrombosis, rivaroxaban showed dose-dependent antithrombotic
      activity. In healthy individuals, rivaroxaban was found to have predictable
      pharmacokinetics and pharmacodynamics across a 5- to 80-mg total daily dose
      range, inhibiting factor Xa activity and prolonging plasma clotting time. In
      phase III clinical trials, rivaroxaban regimens reduced rates of venous
      thromboembolism in patients after total hip or knee arthroplasty compared with
      enoxaparin regimens, without significant differences in rates of major bleeding,
      showing that rivaroxaban has a favorable benefit-to-risk profile.

PMID- 20139358
TI  - Oxidized low-density lipoprotein-activated c-Jun NH2-terminal kinase regulates
      manganese superoxide dismutase ubiquitination: implication for mitochondrial
      redox status and apoptosis.
AB  - OBJECTIVE: Oxidized low-density lipoprotein (oxLDL) modulates intracellular redox
      status and induces apoptosis in endothelial cells. However, the signal pathways
      and molecular mechanism remain unknown. In this study, we investigated the role
      of manganese superoxide dismutase (Mn-SOD) on oxLDL-induced apoptosis via c-Jun
      NH2-terminal kinase (JNK)-mediated ubiquitin/proteasome pathway. METHODS AND
      RESULTS: OxLDL induced JNK phosphorylation that peaked at 30 minutes in human
      aortic endothelial cells. Fluorescence-activated cell sorting analysis revealed
      that oxLDL increased mitochondrial superoxide production by 1.88+/-0.19-fold and
      mitochondrial membrane potential by 18%. JNK small interference RNA (siJNK)
      reduced oxLDL-induced mitochondrial superoxide production by 88.4% and
      mitochondrial membrane potential by 61.7%. OxLDL did not affect Mn-SOD mRNA
      expression, but it significantly reduced Mn-SOD protein level, which was restored
      by siJNK. Immunoprecipitation by ubiquitin antibody revealed that oxLDL increased
      ubiquitination of Mn-SOD, which was inhibited by siJNK. OxLDL-induced caspase-3
      activities were also attenuated by siJNK but were enhanced by Mn-SOD small
      interfering RNA. Furthermore, overexpression of Mn-SOD abrogated oxLDL-induced
      caspase-3 activities. CONCLUSIONS: OxLDL-induced JNK activation regulates
      mitochondrial redox status and Mn-SOD protein degradation via JNK-dependent
      ubiquitination, leading to endothelial cell apoptosis.

PMID- 20139359
TI  - From bystander to commander: how smooth muscle cells promote lymphoid tissue
      neogenesis.

PMID- 20139360
TI  - Blockade of the Ras-extracellular signal-regulated kinase 1/2 pathway is involved
      in smooth muscle 22 alpha-mediated suppression of vascular smooth muscle cell
      proliferation and neointima hyperplasia.
AB  - OBJECTIVE: Vascular smooth muscle cells (VSMCs) can switch between differentiated
      and dedifferentiated phenotypes, and this phenotype switch is believed to be
      essential for repair of vascular injury. We studied the inhibitory effect of
      smooth muscle 22 alpha (SM22 alpha) on VSMC proliferation in vitro and in vivo
      and explored the potential molecular mechanisms of this effect. METHODS AND
      RESULTS: By using coimmunoprecipitation and glutathione S-transferase pull-down
      assays, we have shown that SM22 alpha binds to Ras in SM22 alpha-overexpressed
      VSMCs in the presence or absence of platelet-derived growth factor-BB
      stimulation. SM22 alpha arrested cell cycle progression through segregation of
      Ras with Raf-1 and downregulation of the Raf-1-MEK1/2-extracellular signal
      regulated kinase 1/2 mitogen-activated protein kinase signaling cascade. The
      inhibitory effect of SM22 alpha on VSMC proliferation was verified in vivo. The
      infection of rat carotid arteries with recombinant adenovirus encoding SM22 alpha
      inhibited neointimal hyperplasia via suppression of the Raf-1-MEK1/2
      extracellular signal-regulated kinase 1/2 signaling pathway. CONCLUSIONS: These
      findings suggest that high expression of SM22 alpha inhibits cell proliferation
      via reduction of the response to mitogen stimuli in VSMCs and provide a novel
      mechanism by which VSMCs maintain their contractile phenotype and resist
      mitogenic stimuli in an SM22 alpha-dependent manner.

PMID- 20139361
TI  - Periprocedural anticoagulation management of patients with venous
      thromboembolism.
AB  - OBJECTIVE: Patients with venous thromboembolism (VTE) often require temporary
      warfarin interruption for an invasive procedure. The incidence of thromboembolism
      and bleeding related to periprocedural anticoagulation management of such
      patients is unknown. METHODS AND RESULTS: In a protocol-driven, inception cohort
      design study, all VTE patients (n=775) referred for periprocedural
      anticoagulation management (1997-2007) were followed-up to estimate the 3-month
      cumulative incidence of thromboembolism and bleeding. Patients were stratified by
      thrombus acuity (acute, <30 days; subacute, 31-90 days; or chronic > or =91
      days). Decisions to provide "bridging" low-molecular-weight heparin were based on
      estimated thromboembolism and bleeding risk. Low-molecular-weight heparin was
      more often administered in acute (87%) and subacute (81%) VTE compared to chronic
      VTE (59%; P<0.001). The 3-month cumulative incidence of thromboembolism (1.8%),
      major hemorrhage (1.8%), and mortality (1.7%) were low and did not differ by
      management strategy. Active cancer was the only independent predictor of
      thrombotic recurrence (HR, 4.86; 95% CI, 1.6-14.5; P=0.005), major hemorrhage
      (HR, 6.8; 95% CI, 2.1-21.7; P=0.001), and death (HR, 32.7; 95% CI, 4.3-251.2;
      P=0.0008). CONCLUSIONS: Thromboembolism, bleeding, and death among VTE patients
      in whom anticoagulation is temporarily interrupted for an invasive procedure is
      low. Cancer patients require particular care given their propensity for both
      clotting and bleeding.

PMID- 20139362
TI  - Magnetic resonance molecular imaging of thrombosis in an arachidonic acid mouse
      model using an activated platelet targeted probe.
AB  - OBJECTIVE: Atherosclerotic plaque rupture leads to acute thrombus formation and
      may trigger serious clinical events such as myocardial infarction or stroke.
      Therefore, it would be valuable to identify atherothrombosis and vulnerable
      plaques before the onset of such clinical events. We sought to determine whether
      the noninvasive in vivo visualization of activated platelets was effective when
      using a target-specific MRI contrast agent to identify thrombi, hallmarks of
      vulnerable or high-risk atherosclerotic plaques. METHODS AND RESULTS:
      Inflammatory thrombi were induced in mice via topical application of arachidonic
      acid on the carotid. Thrombus formation was imaged with intravital fluorescence
      microscopy and molecular MRI. To accomplish the latter, a paramagnetic contrast
      agent (P975) that targets the glycoprotein alpha(IIb)beta(3), expressed on
      activated platelets, was investigated. The specificity of P975 for activated
      platelets was studied in vitro. In vivo, high spatial-resolution MRI was
      performed at baseline and longitudinally over 2 hours after injecting P975 or a
      nonspecific agent. The contralateral carotid, a sham surgery group, and a
      competitive inhibition experiment served as controls. P975 showed a good affinity
      for activated platelets, with an IC(50) (concentration of dose that produces 50%
      inhibition) value of 2.6 micromol/L. In thrombosed animals, P975 produced an
      immediate and sustained increase in MRI signal, whereas none of the control
      groups revealed any significant increase in MRI signal 2 hours after injection.
      More important, the competitive inhibition experiment with an alpha(IIb)beta(3)
      antagonist suppressed the MRI signal enhancement, which is indicative for the
      specificity of P975 for the activated platelets. CONCLUSIONS: P975 allowed in
      vivo target-specific noninvasive MRI of activated platelets.

PMID- 20139363
TI  - Inhibition of factor XIa as a new approach to anticoagulation.
AB  - The dose-limiting issue with available anticoagulant therapies is bleeding. Is
      there an approach that could provide antithrombotic protection with reduced
      bleeding? One hypothesis is that targeting proteases upstream from the common
      pathway provides a reduction in thrombin sufficient to impede occlusive
      thrombosis yet allows enough thrombin generation to support hemostasis. The
      impairment of intrinsic coagulation by selective inhibition of factor XI (FXI)
      leaves the extrinsic and common pathways of coagulation intact, making FXI a drug
      target. This concept is supported by the observation that human deficiency in FXI
      results in a mild bleeding disorder compared with other coagulation factor
      deficiencies, and that elevated levels of FXI are a risk factor for
      thromboembolic disease. Moreover, FXI knockout mice have reduced thrombosis with
      little effect on hemostasis. The results from genetic models have been supported
      by studies using neutralizing antibodies, peptide inhibitors, and small-molecule
      inhibitors. These agents impede thrombosis without affecting bleeding time in a
      variety of experimental animals, including primates. Together, these data
      strongly support FXIa inhibition as a viable method to increase the ratio of
      benefit to risk in an antithrombotic drug.

PMID- 20139364
TI  - Current treatment of venous thromboembolism.
AB  - Venous thromboembolism, comprising deep vein thrombosis and pulmonary embolism,
      is a common disorder with at least 250 000 new events occurring each year in the
      United States alone. Treatment of venous thromboembolism includes
      anticoagulation, which is achieved initially with the use of a parenterally
      administered agent followed by a more prolonged course of treatment with an oral
      vitamin K antagonist. The duration of treatment depends on the clinical
      assessment of the benefit-to-risk ratio of prolonged anticoagulation versus the
      risk of recurrent events. In this review, we discuss some of the issues that we
      believe are among the most critical unanswered questions in the management of
      venous thromboembolism in the present era.

PMID- 20139365
TI  - D609 inhibits progression of preexisting atheroma and promotes lesion stability
      in apolipoprotein e-/- mice: a role of phosphatidylcholine-specific phospholipase
      in atherosclerosis.
AB  - OBJECTIVE: Atherosclerosis is considered to be a chronic inflammatory disease.
      Previous research has demonstrated that phosphatidylcholine-specific
      phospholipase C (PC-PLC) plays critical roles in various inflammatory responses.
      However, the association between PC-PLC and atherosclerosis is undetermined.
      Therefore, we sought to investigate whether PC-PLC was implicated in
      atherosclerosis. METHODS AND RESULTS: Immunofluorescence analysis revealed an
      upregulation of PC-PLC in the aortic endothelium from apolipoprotein E-deficient
      (apoE(-/-)) mice. PC-PLC level and activity were also increased in human
      umbilical vein endothelial cells in response to oxidized low-density lipoprotein
      treatment. Pharmacological blockade of PC-PLC by D609 inhibited the progression
      of preexisting atherosclerotic lesions in apoE(-/-) mice and changed the lesion
      composition into a more stable phenotype. Using a combination of pharmacological
      inhibition, polyclonal antibodies, confocal laser scanning microscopy and Western
      blotting, we demonstrated that PC-PLC was required for endothelial expression of
      lectin-like oxidized low-density lipoprotein receptor-1. In addition, D609
      treatment significantly decreased the aortic endothelial expression of the
      vascular cell adhesion molecule-1 and the intercellular adhesion molecule-1.
      Furthermore, inhibition of PC-PLC in human umbilical vein endothelial cells
      reduced the oxidized low-density lipoprotein induced expression of vascular cell
      adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic
      protein-1. CONCLUSIONS: Our data suggest that PC-PLC contributes to the
      progression of atherosclerosis.

PMID- 20139366
TI  - SERCA2b activity is regulated by cyclophilins in human platelets.
AB  - OBJECTIVE: The role of cyclophilins (chaperones that are widely expressed in
      different cell types, including human platelets) was explored in sarcoendoplasmic
      calcium (Ca(2+)) adenosine triphosphatase (SERCA) activity. METHODS AND RESULTS:
      Cyclophilin inhibition by cyclosporin A (CsA) evoked a time- and concentration
      dependent reduction of Ca(2+) uptake by SERCA2b. However, other Ca(2+)-adenosine
      triphosphatases expressed in platelets, such as SERCA3 and plasma membrane Ca(2+)
      adenosine triphophatase, remained unaltered after CsA treatment. Cypermethrin, a
      non-CsA-related calcineurin inhibitor, did not alter SERCA2b activity.
      Furthermore, SERCA2b was affected by other CsA analogues, which do not interfere
      with calcineurin, such as PKF-211-811-NX5 (NIM811) and sanglifehrin A. Inhibition
      of the immunophilin family members using FK506 (tacrolimus) did not alter SERCA2b
      ability to sequester Ca(2+) into the dense tubular system. Coimmunoprecipitation
      experiments confirmed that cyclophilin A associates with SERCA2b and stromal
      interaction molecule-1 in resting platelets. This interaction is attenuated by
      the physiological agonist thrombin but enhanced by treatment with CsA or
      sanglifehrin A. CONCLUSIONS: Cyclophilin A is a regulator of SERCA2b in human
      platelets.

PMID- 20139368
TI  - Assigning "frailty".

PMID- 20139367
TI  - Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizer-like
      cells on combined tumor necrosis factor receptor-1/lymphotoxin beta-receptor NF
      kappaB signaling.
AB  - OBJECTIVE: Mouse aorta smooth muscle cells (SMC) express tumor necrosis factor
      receptor superfamily member 1A (TNFR-1) and lymphotoxin beta-receptor (LTbetaR).
      Circumstantial evidence has linked the SMC LTbetaR to tertiary lymphoid
      organogenesis in hyperlipidemic mice. Here, we explored TNFR-1 and LTbetaR
      signaling in cultured SMC. METHODS AND RESULTS: TNFR-1 signaling activated the
      classical RelA NF-kappaB pathway, whereas LTbetaR signaling activated the
      classical RelA and alternative RelB NF-kappaB pathways, and both signaling
      pathways synergized to enhance p100 inhibitor processing to the p52 subunit of NF
      kappaB. Microarrays showed that simultaneous TNFR-1/LTbetaR activation resulted
      in elevated mRNA encoding leukocyte homeostatic chemokines CCL2, CCL5, CXCL1, and
      CX3CL1. Importantly, SMC acquired features of lymphoid tissue organizers, which
      control tertiary lymphoid organogenesis in autoimmune diseases through
      hyperinduction of CCL7, CCL9, CXCL13, CCL19, CXCL16, vascular cell adhesion
      molecule-1, and intercellular adhesion molecule-1. TNFR-1/LTbetaR cross-talk
      resulted in augmented secretion of lymphorganogenic chemokine proteins.
      Supernatants of TNFR-1/LTbetaR-activated SMC markedly supported migration of
      splenic T cells, B cells, and macrophages/dendritic cells. Experiments with ltbr(
      /-) SMC indicated that LTbetaR-RelB activation was obligatory to generate the
      lymphoid tissue organizer phenotype. CONCLUSIONS: SMC may participate in the
      formation of tertiary lymphoid tissue in atherosclerosis by upregulation of
      lymphorganogenic chemokines involved in T-lymphocyte, B-lymphocyte, and
      macrophage/dendritic cell attraction.

PMID- 20139370
TI  - Advanced identification of proteins in uncharacterized proteomes by pulsed in
      vivo stable isotope labeling-based mass spectrometry.
AB  - Despite progress in the characterization of their genomes, proteomes of several
      model organisms are often only poorly characterized. This problem is aggravated
      by the presence of large numbers of expressed sequence tag clones that lack
      homologues in other species, which makes it difficult to identify new proteins
      irrespective of whether such molecules are involved in species-specific
      biological processes. We have used a pulsed stable isotope labeling with amino
      acids in cell culture (SILAC)-based mass spectrometry method, which is based on
      the detection of paired peptides after [(13)C(6)]lysine incorporation into
      proteins in vivo, to greatly increase the confidence of protein identification in
      cross-species database searches. The method was applied to identify nearly 3000
      proteins in regenerating tails of the urodele amphibian Notophthalmus
      viridescens, which possesses outstanding capabilities in the regeneration of
      complex tissues. We reason that pulsed in vivo SILAC represents a versatile tool
      to identify new proteins in species for which only limited sequence information
      exists.

PMID- 20139373
TI  - Response to earlier letter.

PMID- 20139371
TI  - Differential protein expression profiling by iTRAQ-two-dimensional LC-MS/MS of
      human bladder cancer EJ138 cells transfected with the metastasis suppressor KiSS
      1 gene.
AB  - KiSS-1 is a metastasis suppressor gene reported to be involved in the progression
      of several solid neoplasias. The loss of KiSS-1 gene expression has been shown to
      be inversely correlated with increasing tumor stage, distant metastases, and poor
      overall survival in bladder tumors. To identify the molecular pathways associated
      with the metastasis suppressor role of KiSS-1 in bladder cancer, we carried out a
      proteomics analysis of bladder cancer cells (EJ138) transiently transfected with
      a vector encompassing the full-length KiSS-1 gene using an iTRAQ (isobaric tags
      for relative and absolute quantitation) approach. Protein extracts collected
      after 24- and 48-h transfection were fractionated and cleaved with trypsin, and
      the resulting peptides were labeled with iTRAQ reagents. The labeled peptides
      were separated by strong cation exchange and reversed phase LC and analyzed by
      MALDI-TOF/TOF MS. Three software packages were utilized for data analysis:
      ProteinPilot for identification and quantification of differentially expressed
      proteins, Protein Center for gene ontology analysis, and Ingenuity Pathways
      Analysis to provide insight into biological networks. Comparative analysis among
      transfected, mock, and empty vector-exposed cells identified 1529 proteins with
      high confidence (>99%) showing high correlation rates among replicates (70%). The
      involvement of the identified proteins in biological networks served to
      characterize molecular pathways associated with KiSS-1 expression and to select
      critical candidates for verification analyses by Western blot using independent
      transfected replicates. As part of complementary clinical validation strategies,
      immunohistochemical analyses of proteins regulated by KiSS-1, such as Filamin A,
      were performed on bladder tumors spotted onto tissue microarrays (n = 280). In
      summary, our study not only served to uncover molecular mechanisms associated
      with the metastasis suppressor role of KiSS-1 in bladder cancer but also to
      reveal the biomarker role of Filamin A in bladder cancer progression and clinical
      outcome.

PMID- 20139374
TI  - Self-poisoning in older patients.

PMID- 20139375
TI  - Dysregulation of the Wnt/beta-catenin signaling pathway in canine cutaneous
      melanotic tumor.
AB  - The Wnt/beta-catenin signal transduction pathway is important in many
      developmental processes and during tumorigenesis. beta-Catenin acts as a signal
      transducer. To investigate whether the Wnt/beta-catenin signal transduction
      pathway is involved in canine cutaneous melanomagenesis, 18 formalin-fixed
      paraffin-embedded canine cutaneous melanotic tumor tissues were examined. For
      cloning and sequencing of the full-length canine ctnnb1 gene encoding beta
      catenin, conserved sequences of the human and mouse ctnnb1 gene were used to
      design the primers. For analysis of expression and translocation of beta-catenin
      in canine cutaneous melanotic tumors, semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemistry were performed. The
      canine ctnnb1 sequence showed a high degree of similarity to those of human and
      mouse. Semiquantitative RT-PCR showed a substantial increase in expression of
      ctnnb1 mRNA in canine cutaneous melanotic tumors compared to normal canine
      melanocytes, regardless of whether the tumor was benign or malignant.
      Immunohistochemistry revealed cytoplasmic accumulation of beta-catenin in
      melanotic tumors. In melanoma tissues, nuclear translocation of beta-catenin was
      also observed. The present study demonstrated that abnormal intracellular
      accumulation and substantially increased expression of beta-catenin are involved
      in canine cutaneous melanotic tumor.

PMID- 20139376
TI  - The Portuguese version of the Breastfeeding Self-Efficacy Scale-Short Form.
AB  - The objective of this study was to translate and psychometrically assess a
      Portuguese version of the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF).
      The original English version of the BSES-SF was translated to Portuguese and
      tested among a sample of 89 mothers in southern Brazil from the 2nd to 12th
      postpartum week followed by face-to-face interviews. The mean total score of the
      Portuguese version of the BSES-SF was 63.6 +/- 6.22. The reliability analysis of
      each item in the scale attained significant Cronbach's alphas of 0.63 or
      superior. The Cronbach's alpha generated by the entire range of 14 questions was
      0.71. A factor analysis identified one factor that contributed to 20% of the
      variance. This study demonstrates that the original English version of the BSES
      SF was successfully adapted to Portuguese. The Portuguese version of the BSES-SF
      constitutes a reliable research instrument for evaluating breastfeeding self
      efficacy in Brazil.

PMID- 20139377
TI  - Breastfeeding in preterm and term twins--maternal factors associated with early
      cessation: a population-based study.
AB  - To investigate the duration of breastfeeding and the impact of maternal factors
      for cessation of breastfeeding in twin infants, the authors undertook a
      population-based cohort study. Breastfeeding data obtained from Child Health
      Centres were matched with data on infant and maternal demographics from Swedish
      national registers. A total of 1.657 twins were included, of whom 695 were born
      preterm. Breastfeeding frequencies in preterm twins were 79% at 2 months, 58% at
      4 months, 39% at 6 months, 14% at 9 months, and 6% at 12 months. In term twins,
      the corresponding frequencies were 84%, 63%, 45%, 18%, and 6%, respectively. In
      both preterm and term mothers, mothers who had a lower educational level or
      smoked at first antenatal care visit were subject to earlier cessation of
      breastfeeding by 6 months of age. In addition, in mothers of term infants,
      mothers who were < 23 years old or primiparous had a higher risk for cessation of
      breastfeeding before 6 months. Thus, mothers of twins have a good potential to
      breastfeed, but additional support is needed for those more susceptible to early
      cessation of breastfeeding.

PMID- 20139378
TI  - International disease monitoring, October to December 2009.

PMID- 20139379
TI  - Number and ownership profiles of cats and dogs in the UK.
AB  - A random sample of 2980 households in the UK in 2007 showed that 26 per cent and
      31 per cent of households owned cats and dogs, respectively. Households with
      gardens were more likely to own cats and dogs than households without gardens.
      Households in which someone was qualified to degree level were more likely to own
      cats and less likely to own dogs than other households. Cats were more likely to
      be owned by semi-urban/rural households and by female respondents. Dog ownership
      significantly decreased the likelihood of cat ownership, and respondents aged 65
      years or more were less likely to report that their household owned a cat than
      younger respondents. Households with one or more dogs and children aged 11 to 15
      years were more likely to own a cat than other households. The likelihood of dog
      ownership increased as household size increased. Dogs were more likely to be
      owned by rural households, and less likely to be owned by households with cats or
      children aged 10 years or younger. Female respondents and those aged less than 55
      years were more likely to report dog ownership than other respondents. The
      estimated size (and 95 per cent confidence intervals) of the owned cat and dog
      populations in the UK in 2006 was 10,332,955 (9,395,642 to 11,270,269) cats and
      10,522,186 (9,623,618 to 11,420,755) dogs.

PMID- 20139380
TI  - Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a
      phaeochromocytoma.
AB  - Urinary adrenaline (epinephrine), noradrenaline, dopamine, metadrenaline
      (metanephrine) and normetadrenaline to creatinine ratios were measured from spot
      samples of seven client-owned dogs with a histologically confirmed
      phaeochromocytoma. Urine was collected on day 0 in the hospital in six dogs, and
      additionally on days 2, 6 and 7 after discharge in two of these dogs. In one dog,
      urine was sampled on day 7 only. Samples were also collected from 10 healthy
      control dogs on days 0, 1 and 7. In dogs with phaeochromocytomas,
      normetadrenaline:creatinine ratios at all time points ranged from 103 to 6430
      nmol/mmol. From day 0, ratios of samples taken at the hospital (range 157 to 925
      nmol/mmol) were significantly higher (P<0.0012) compared with control samples
      (range 14 to 91 nmol/mmol). The highest normetadrenaline:creatinine ratios were
      found in two dogs with bilateral phaeochromocytomas. Adrenaline:creatinine and
      noradrenaline:creatinine ratios were also significantly increased (P<0.016) in
      dogs with a phaeochromocytoma at day 0 compared with controls, although the
      difference was less pronounced than that between controls and dogs with a
      phaeochromocytoma for the normetadrenaline:creatinine ratio. Urine
      normetadrenaline:creatinine ratios may be useful in the diagnosis of canine
      phaeochromocytomas.

PMID- 20139381
TI  - Cutaneous TB caused by Mycobacterium bovis in a veterinary surgeon following
      exposure to a tuberculous alpaca (Vicugna pacos).

PMID- 20139382
TI  - Outbreak of rhinitis caused by equine herpesvirus type 3.

PMID- 20139384
TI  - Official Veterinarian fee review.

PMID- 20139385
TI  - Use of antibiotics.

PMID- 20139386
TI  - Angiostrongylus vasorum infection in a stoat.

PMID- 20139387
TI  - Pathogenesis and treatment of anemia in inflammatory bowel disease.

PMID- 20139388
TI  - Molecular basis of juvenile myelomonocytic leukemia.

PMID- 20139389
TI  - High hematocrit as a risk factor for venous thrombosis. Cause or innocent
      bystander?

PMID- 20139390
TI  - Stem cell transplantation for autoimmune diseases.

PMID- 20139391
TI  - Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves
      rapid and durable cytogenetic responses and high transformation-free survival
      rates in chronic phase chronic myeloid leukemia patients with resistance,
      suboptimal response or intolerance to imatinib.
AB  - BACKGROUND: Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase
      inhibition and is approved for chronic-phase chronic myeloid leukemia patients
      resistant or intolerant to imatinib. To better assess durability of response to
      and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose
      optimization study in chronic-phase chronic myeloid leukemia are reported here.
      DESIGN AND METHODS: In a phase 3 study, 670 chronic-phase chronic myeloid
      leukemia patients with resistance, intolerance, or suboptimal response to
      imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140
      mg once-daily, or 70 mg twice-daily. RESULTS: Data from a 2-year minimum follow
      up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic
      response and complete cytogenetic response rates comparable to those in the other
      treatment arms, and reduces the frequency of key side effects. Comparable 2-year
      progression-free survival and overall survival rates were observed (80% and 91%,
      respectively, for 100 mg once daily, and 75%-76% and 88%-94%, respectively, in
      other arms). Complete cytogenetic responses were achieved rapidly, typically by 6
      months. In patients treated with dasatinib 100 mg once daily for 6 months without
      complete cytogenetic response, the likelihood of achieving such a response by 2
      years was 50% for patients who had achieved a partial cytogenetic response, and
      only 8% or less for patients with minor, minimal, or no cytogenetic response.
      Less than 3% of patients suffered disease transformation to accelerated or blast
      phase. CONCLUSIONS: Intermittent kinase inhibition can achieve rapid and durable
      responses, indistinguishable from those achieved with more continuous inhibition.

PMID- 20139392
TI  - Lymphoma stem cells: enough evidence to support their existence?
AB  - While leukemia-originating stem cells are critical in the initiation and
      maintenance of leukemias, the existence of similar cell populations that may
      generate B-cell lymphoma upon mutation remains uncertain. Here we propose that
      committed lymphoid progenitor/precursor cells with an active V-D-J recombination
      program are the initiating cells of follicular lymphoma and mantle cell lymphoma
      when targeted by immunoglobulin (IG)- gene translocations in the bone marrow.
      However, these pre-malignant lymphoma-initiating cells cannot drive complete
      malignant transformation, requiring additional cooperating mutations in specific
      stem-cell programs to be converted into the lymphoma-originating cells able to
      generate and sustain lymphoma development. Conversely, diffuse large B-cell
      lymphoma and sporadic Burkitt's lymphoma derive from B lymphocytes that acquire
      translocations through IG-hyper-mutation or class-switching errors within the
      germinal center. Although secondary reprogramming mutations are generally
      required, some cells such as centroblasts or memory B cells that have certain
      stem cell-like features, or lymphocytes with MYC rearrangements that deregulate
      self-renewal pathways, may bypass this need and directly function as the lymphoma
      originating cells. An alternative model supports an aberrant epigenetic
      modification of gene sets as the first occurring hit, which either leads to
      retaining stem-cell features in hematopoietic stem or progenitor cells, or
      reprograms stemness into more committed lymphocytes, followed by secondary
      chromosomal translocations that eventually drive lymphoma development. Isolation
      and characterization of the cells that are at the origin of the different B-cell
      non-Hodgkin's lymphomas will provide critical insights into the disease
      pathogenesis and will represent a step towards the development of more effective
      therapies.

PMID- 20139393
TI  - Peripheral neuropathy and new treatments for multiple myeloma: background and
      practical recommendations.
AB  - In multiple myeloma, peripheral neuropathy has for a long time been considered as
      mainly secondary to the plasma cell dyscrasia itself. With the advent of new
      targeted drugs such as thalidomide and bortezomib, the iatrogenic neurotoxicity
      has become the leading cause of peripheral neuropathy. This review discusses the
      pathogenesis, incidence, risk factors, diagnosis, characteristics, and management
      of peripheral neuropathy related to new multiple myeloma drugs, mainly bortezomib
      and thalidomide. The current knowledge of the pathophysiology of the new forms of
      peripheral neuropathy is still limited. The mechanisms involved depend on the
      agents used, patient's medical history, and duration of exposure and/or treatment
      doses or sequence. Diagnosis of such peripheral neuropathy is often easier than
      treatment. A full anamnesis and regular clinical evaluation are necessary.
      Electrophysiological assessments may support the diagnosis, although their
      contribution remains insufficient. Complex clinical features may require a
      specialized neurological assessment within the context of a multi-disciplinary
      approach. Finally, early detection of peripheral neuropathy and the use of dose
      adjustment algorithms as in the case of bortezomib, should help reduce the side
      effects while maintaining anti-tumor efficacy.

PMID- 20139394
TI  - Treatment with mycophenolate mofetil followed by recombinant human erythropoietin
      in patients with low-risk myelodysplastic syndromes resistant to erythropoietin
      treatment.

PMID- 20139396
TI  - Retraction. The integrin {alpha}9{beta}1 on hematopoietic stem and progenitor
      cells: involvement in cell adhesion, proliferation and differentiation.

PMID- 20139397
TI  - Hospital safety climate and safety outcomes: is there a relationship in the VA?
AB  - Strengthening safety climate is recognized as a necessary strategy for improving
      patient safety. Yet there is little empirical evidence linking hospitals' safety
      climate with safety outcomes.The authors explored the potential relationship
      between safety climate and Veterans Health Administration hospital safety
      performance using the Patient Safety Indicator (PSI) rates. Safety climate survey
      data were merged with hospital discharge data to calculate PSIs. Linear
      regressions examined the relationship between hospitals' safety climate and
      dimensions of safety climate with individual PSIs and a PSI composite measure,
      controlling for organizational-level variables. Safety climate overall was not
      related to the PSIs or to the PSI composite, although a few individual dimensions
      of safety climate were associated with specific PSIs. Perceptions of frontline
      staff were more closely aligned with PSIs than those of senior managers.

PMID- 20139398
TI  - Lost the feel for the game: meanings of onset and diagnosis of AIDS dementia for
      significant others.
AB  - The onset and diagnosis of AIDS dementia marks a new dimension to living with
      HIV, an aspect few imagine or are equipped for. As a result of the profound
      changes that AIDS dementia makes to the ways the person with HIV acts, the life
      of significant others is similarly altered. Drawing on the metaphor of "the game"
      from Bourdieu's work on habitus, I explore how the onset and subsequent diagnosis
      of AIDS dementia comes to signify for significant others a moment in which life
      is permanently altered, whereby they no longer have the feel for the game. With
      AIDS dementia, life ("the game") is altered. Significant others feel that AIDS
      dementia is not a normal or acceptable AIDS illness: fears are contested, secrets
      managed and disclosed, and relations strained. This change in play further
      marginalizes significant others, and increases their sense of alterity from
      others living with and affected by HIV alone, because dementia is not the
      socially acceptable way of being ill with HIV.

PMID- 20139399
TI  - The research relationship as a facilitator of remoralization and self-growth:
      postearthquake suffering and healing.
AB  - In new-paradigm research, empathic witnessing by the researcher might create
      within the researcher-participant relationship a space for participants to share
      and transcend their suffering. I explore this theme through the constructionist
      grounded theory analysis of interviews, fieldnotes, and my self-reflexive
      commentary from an original study conducted to understand the experiences of
      suffering and healing among the survivors of an earthquake that occurred in India
      in 2001. The five categories that emerged--getting overwhelmed while verbalizing
      suffering, search for the cultural meaning of the research relationship, piecing
      together of self, reaffirmation of moral status, and continuing bond revalidating
      the self--provide insights about this theme. Also, my reflections on
      participants' suffering and healing not only facilitated my healing but also
      inspired me to expand my boundary of I to feel "oneness" with all forms of nature
      or existence. The findings and discussion not only enhance understanding of the
      communications and complexities of the researcher-participant relationship, but
      indicate the nature of support and education needed if researchers are to be
      effective witnesses to suffering.

PMID- 20139400
TI  - Long-term oral baclofen treatment in a child with cerebral palsy:
      electroencephalographic changes and clinical adverse effects.
AB  - Baclofen is widely used to control spasticity in children with cerebral palsy.
      Several publications described clinical adverse effects of baclofen oral
      treatment, but the effect of baclofen on seizure potentiation is still
      controversial. We describe a 10-year-old female patient with cerebral palsy,
      epilepsy, and mental retardation who developed clinical adverse effects
      (confusion, agitated state, insomnia, diffuse hypotonia, and hyporeflexia) and
      electroencephalographic (EEG) changes (quasiperiodic, generalized burst of sharp
      waves that take up >50% of standard EEG) during long-term oral baclofen
      treatment, after gradually increasing the dosage but still within the therapeutic
      dose. Our case showed clearly that the EEG changes in our patient, with a history
      of epilepsy in good control, have been induced by the baclofen increase, and we
      describe the possible mechanisms that could explain proconvulsive effect of
      baclofen.

PMID- 20139401
TI  - Atypical propositional language organization in prenatal and early-acquired
      temporal lobe lesions.
AB  - This study investigated differences in propositional language organization in
      children with developmental and acquired brain lesions. We evaluated 30 right
      handed subjects with intractable epilepsy due to either focal cortical dysplasia
      or hippocampal sclerosis with neuropsychological testing and functional MRI prior
      to epilepsy surgery. Atypical activations were seen in both prenatal and early
      postnatal lesions, but the contribution of specific histopathological substrate
      was minimal. Atypical organization of both temporal and frontal language areas
      also correlated inversely with receptive vocabulary scores. The data demonstrated
      a greater propensity toward atypical activation patterns for receptive than
      expressive networks, particularly when lesions were located in the dominant
      temporal lobe. Atypical language organization was not correlated with seizure
      related factors such as age at onset or duration of epilepsy. The patterns of
      atypical language activation support prior studies implicating proximity of
      pathology to eloquent cortex in the dominant hemisphere as the primary
      determinant of functional reorganization.

PMID- 20139402
TI  - Unusual spinal tuberculosis with cord compression in an infant.
AB  - Spinal abscess is rare in children, especially in young infants. The most common
      etiology is bacteria, Staphylococcus aureus in particular. Mycobacterium
      tuberculosis is another cause. We report an unusual cervical spinal abscess with
      spinal cord compression in a 13-month-old child. The presenting symptoms were
      weakness in the right arm and, predominantly, the right leg for 1 month. Magnetic
      resonance imaging showed an abscess of the cervical spine, extension with bony
      destruction, and spinal cord compression. The patient underwent an emergency
      neurosurgical decompression and laminectomy. Pathology and culture results
      confirmed Mycobacterium tuberculosis. After 12 months of antituberculosis
      treatment, the child could walk with a walker. At 37 months, he was able to walk
      without assistance. We conclude that spinal tuberculosis should be considered in
      cases of children with spinal cord-compression symptoms and an image showing an
      extraspinal abscess. Early diagnosis and prompt treatment are critical for
      maximizing a functional recovery.

PMID- 20139403
TI  - Corpus callosum segment circumference is associated with response control in
      children with attention-deficit hyperactivity disorder (ADHD).
AB  - Response control is impaired in attention-deficit hyperactivity disorder (ADHD).
      Given the corpus callosum's role in response control, we compared callosal
      morphology in 64 children with ADHD and 64 typically developing children, aged 7
      to 13 years, and investigated the relationships between callosal morphology and
      response control. Area and circumference of 5 callosal segments (genu, rostral
      body, midbody, isthmus, and splenium) were normalized for cerebral volume and
      examined for correlation with mean reaction time, intrasubject variability,
      and/or commission error rate from a go/no-go task. There were no between-group
      differences in segment areas or circumferences. Reaction time correlated with
      midbody circumference for boys with ADHD and isthmus circumference for girls with
      ADHD. For the entire cohort, rostral body circumference correlated with
      intrasubject variability. Impaired response control in ADHD is associated with
      anomalies in frontal interhemispheric connections. Future studies examining
      callosal shape will illuminate the anatomic basis of correlations between
      callosal segment circumference and response control.

PMID- 20139404
TI  - Midazolam or diazepam administration during electroencephalography helps to
      diagnose subacute sclerosing panencephalitis (SSPE).
AB  - Although diagnostic contribution of intravenous diazepam administration during
      electroencephalography (EEG) recording in subacute sclerosing panencephalitis has
      been known, no another drug with less potential side effects has been studied in
      this procedure. In this study, diazepam is compared with midazolam in 25 subacute
      sclerosing panencephalitis-diagnosed children and 10 children with subacute
      sclerosing panencephalitis-suggesting symptoms, normal EEG findings and no
      certain diagnosis. Neither midazolam nor diazepam affected typical periodic slow
      wave complexes. However, in the patients with atypical EEG abnormalities,
      midazolam, like diazepam, attenuated sharp or sharp-and-slow waves, and therefore
      made the identification of periodic slow-wave paroxysms easier. In the patients
      with normal EEGs, both midazolam and diazepam revealed typical periodic complexes
      on EEG recording in the same 3 patients. Cerebrospinal fluid examination verified
      the diagnosis of subacute sclerosing panencephalitis. The findings suggest that
      midazolam or diazepam administration increases the contribution of EEG recording
      in atypical cases with subacute sclerosing panencephalitis.

PMID- 20139405
TI  - Midbrain and spinal cord magnetic resonance imaging (MRI) changes in
      poliomyelitis.
AB  - Poliomyelitis, though eradicated from most parts of the world, continues to occur
      in India. There is paucity of data on the magnetic resonance imaging (MRI)
      changes in poliomyelitis. We report a 3(1/2)-year-old boy who presented with
      subacute onset flaccid paralysis and altered sensorium. Stool culture was
      positive for wild polio virus type 3. Magnetic resonance imaging revealed signal
      changes in bilateral substantia nigra and anterior horns of the spinal cord.
      These MRI changes may be of potential diagnostic significance in a child with
      poliomyelitis.

PMID- 20139406
TI  - Alanine-shaving mutagenesis to determine key interfacial residues governing the
      assembly of a nano-cage maxi-ferritin.
AB  - The fundamental process of protein self-assembly is governed by protein-protein
      interactions between subunits, which combine to form structures that are often on
      the nano-scale. The nano-cage protein, bacterioferritin from Escherichia coli, a
      maxi-ferritin made up of 24 subunits, was chosen as the basis for an alanine
      shaving mutagenesis study to discover key amino acid residues at symmetry-related
      protein-protein interfaces that control protein stability and self-assembly. By
      inspection of these interfaces and "virtual alanine scanning," nine mutants were
      designed, expressed, purified, and characterized using transmission electron
      microscopy, size exclusion chromatography, dynamic light scattering, native PAGE,
      and temperature-dependent CD. Many of the selected amino acids act as hot spot
      residues. Four of these (Arg-30, which is located at the two-fold axis, and Arg
      61, Tyr-114, and Glu-128, which are located at the three-fold axis), when
      individually mutated to alanine, completely shut down detectable solution
      formation of 24-mer, favoring a cooperatively folded dimer, suggesting that they
      may be oligomerization "switch residues." Furthermore, two residues, Arg-30 and
      Arg-61, when changed to alanine form mutants that are more thermodynamically
      stable than the native protein. This investigation into the structure and
      energetics of this self-assembling nano-cage protein not only can act as a
      jumping off point for the eventual design of novel protein nano-structures but
      can also help to understand the role that structure plays on the function of this
      important class of proteins.

PMID- 20139407
TI  - Polymerized type I collagen reduces chronic cyclosporine nephrotoxicity.
AB  - BACKGROUND: Polymerized type I collagen (P-collagen) has been successfully used
      to reduce human hypertrophic scars due to its anti-fibrotic and anti-inflammatory
      properties. We therefore carried out a study to determine if P-collagen reduces
      functional and structural injury in chronic cyclosporine [cyclosporine A (CsA)]
      nephropathy. METHODS: Four groups of six male Wistar rats fed with a low sodium
      diet were treated with vehicle, P-collagen (0.8 mg/day, i.p.), CsA (15 mg/kg) or
      CsA + P-collagen for 15 days. Mean arterial pressure, renal blood flow and
      glomerular filtration rate were measured in all groups. Structural injury such as
      arteriolopathy, tubulo-interstitial fibrosis (TI-fibrosis) and positive apoptotic
      cells were quantified. The mRNA expression levels of transforming growth factor
      beta (TGF-beta), kidney injury molecule (Kim-1), alpha-smooth muscle actin (alpha
      SMA), glutathione peroxidase, catalase and Cu/Zn superoxide dismutase (SOD) as
      well as MnSOD were assessed. Antioxidant enzyme activity, renal lipoperoxidation
      and urinary excretion of oxygen peroxide (UH(2)O(2)V) were determined. RESULTS:
      Cyclosporine produced renal dysfunction and induced the development of
      arteriolopathy, TI-fibrosis and tubular apoptosis. These alterations were
      associated with increases in TGF-beta, Kim-1 and alpha-SMA mRNA levels as well as
      with a significant increase of oxidative stress and a reduction of SOD activity.
      P-Collagen partially ameliorated CsA-induced renal dysfunction and structural
      injury and prevented both tubular apoptosis and increased oxidative stress. This
      renoprotective effect was found to be associated with a reduction of TGF-beta,
      Kim-1 and alpha-SMA mRNA levels. CONCLUSIONS: This study has therefore
      demonstrated that P-collagen appears to have anti-fibrotic and anti-apoptotic
      properties and highlights the possibility that the compound might be useful in a
      strategy to reduce chronic CsA nephrotoxicity.

PMID- 20139408
TI  - Disease classification: a pitfall of the ERA/EDTA registry?

PMID- 20139409
TI  - Systems biology: opening new avenues in clinical research.

PMID- 20139410
TI  - Child neurology practice and neurological disorders in East Africa.
AB  - Neurological disorders, including neurodevelopmental disorders, have been
      identified by the World Health Organization (WHO) as one of the greatest threats
      to global public health. It is generally believed that these conditions are more
      prevalent in the developing than the developed world because of multiple known
      risk factors such as infections, malnutrition, and limited resources for
      obstetric and neonatal management. In East Africa, few investigations have been
      conducted to obtain data on the magnitude and description of neurological
      disorders among children, and the practice of child neurology is faced with
      challenges cutting across areas of health personnel, patient diagnosis,
      management, and rehabilitation. This article reviews the burden, types, and
      causes of neurological disorders in the East African region. The challenges and
      successes in the practice of child neurology and recommendations for the future
      are discussed.

PMID- 20139411
TI  - The effect of hydrocortisone on neurodevelopmental outcome in premature infants
      less than 29 weeks' gestation.
AB  - The use of postnatal dexamethasone in premature newborns can be associated with a
      deleterious neurodevelopmental outcome. The effect of hydrocortisone on
      developmental outcome in these patients is less clear. We therefore sought to
      examine the effect of hydrocortisone on early developmental outcome in premature
      newborns. We retrospectively examined the effect of hydrocortisone on
      developmental outcome during the first 2 years of life in premature infants <29
      weeks' gestation at birth. Even though hydrocortisone was used in infants with a
      greater risk for poor outcome, its use, unless prolonged >7 days, was generally
      not associated with a worse developmental outcome or higher rate of referral for
      early intervention. A short course of hydrocortisone in sick premature newborns
      does not appear to have a deleterious effect on developmental outcome.

PMID- 20139412
TI  - Pilot study of a novel computerized task to assess spatial learning in children
      and adolescents with neurofibromatosis type 1.
AB  - Difficulties with visual-spatial learning are frequently observed and often
      considered to be the hallmark of neurocognitive impairment in neurofibromatosis
      type 1. The computerized Arena Maze is a virtual environment task that has been
      developed as a human paradigm to the Morris Water Maze, which is used to evaluate
      spatial learning in animal models. The authors evaluated this task as a measure
      of spatial learning in children with neurofibromatosis type 1 compared with their
      unaffected siblings. Affected children were able to learn the task and navigate
      the virtual environment; however, they performed more poorly on standard measures
      of spatial learning and spatial working memory than their siblings. The group
      with neurofibromatosis type 1 demonstrated decreased proficiency in earlier
      target trials and had more difficulty in remembering target location. This study
      demonstrates the potential utility of a novel virtual task to assess spatial
      learning deficits in children with neurofibromatosis type 1.

PMID- 20139413
TI  - APOE epsilon4: a potential modulation factor in Rett syndrome.
AB  - Rett syndrome is a neurodevelopmental disorder mainly caused by de novo mutations
      in the MECP2 (methyl-CpG-binding protein 2) gene. There is considerable variation
      in the severity of clinical features among Rett syndrome patients, even among
      patients with the same MECP2 mutation. In addition to X-chromosome inactivation
      pattern, the genetic background of the affected individual might also have a role
      in determining the severity of the disorder. We suggest that APOE is one of the
      genetic modulating factors. We analyzed clinical phenotypes of 46 patients with
      Rett syndrome, with confirmed MECP2 mutation. We discovered that among epsilon4
      carriers, some clinical features were more severe, and the developmental
      regression occurred 4 months earlier on average than in those without the
      epsilon4 allele. Earlier onset of regression suggests a possible trend; however,
      it did not achieve distinctive statistical significance. Nevertheless, the
      epsilon4 allele of APOE may serve as a candidate modulation factor for the Rett
      syndrome phenotype.

PMID- 20139414
TI  - Nox4 B-loop creates an interface between the transmembrane and dehydrogenase
      domains.
AB  - By targeting redox-sensitive amino acids in signaling proteins, the NADPH oxidase
      (Nox) family of enzymes link reactive oxygen species to physiological processes.
      We previously analyzed the sequences of 107 Nox enzymes and identified conserved
      regions that are predicted to have important functions in Nox structure or
      activation. One such region is the cytosolic B-loop, which in Nox1-4 contains a
      conserved polybasic region. Previous studies of Nox2 showed that certain basic
      residues in the B-loop are important for activity and translocation of
      p47(phox)/p67(phox), suggesting this region participates in subunit assembly.
      However, conservation of this region in Nox4, which does not require
      p47(phox)/p67(phox), suggested an additional role for the B-loop in Nox function.
      Here, we show by mutation of Nox4 B-loop residues that this region is important
      for Nox4 activity. Fluorescence polarization detected binding between Nox4 B-loop
      peptide and dehydrogenase domain (K(d) = 58 +/- 12 nm). This interaction was
      weakened with Nox4 R96E B-loop corresponding to a mutation that also markedly
      decreases the activity of holo-Nox4. Truncations of the dehydrogenase domain
      localize the B-loop-binding site to the N-terminal half of the NADPH-binding
      subdomain. Similarly, the Nox2 B-loop bound to the Nox2 dehydrogenase domain, and
      both the Nox2 and Nox4 interactions were dependent on the polybasic region of the
      B-loop. These data indicate that the B-loop is critical for Nox4 function; we
      propose that the B-loop, by binding to the dehydrogenase domain, provides the
      interface between the transmembrane and dehydrogenase domains of Nox enzymes.

PMID- 20139415
TI  - A real-time assay for CpG-specific cytosine-C5 methyltransferase activity.
AB  - A real-time assay for CpG-specific cytosine-C5 methyltransferase activity has
      been developed. The assay applies a break light oligonucleotide in which the
      methylation of an unmethylated 5'-CG-3' site is enzymatically coupled to the
      development of a fluorescent signal. This sensitive assay can measure rates of
      DNA methylation down to 0.34 +/- 0.06 fmol/s. The assay is reproducible, with a
      coefficient of variation over six independent measurements of 4.5%. Product
      concentration was accurately measured from fluorescence signals using a linear
      calibration curve, which achieved a goodness of fit (R(2)) above 0.98. The
      oligonucleotide substrate contains three C5-methylated cytosine residues and one
      unmethylated 5'-CG-3' site. Methylation yields an oligonucleotide containing the
      optimal substrate for the restriction enzyme GlaI. Cleavage of the fully
      methylated oligonucleotide leads to separation of fluorophore from quencher,
      giving a proportional increase in fluorescence. This method has been used to
      assay activity of DNMT1, the principle maintenance methyltransferase in human
      cells, and for the kinetic characterization of the bacterial cytosine-C5
      methyltransferase M.SssI. The assay has been shown to be suitable for the real
      time monitoring of DNMT1 activity in a high-throughput format, with low
      background signal and the ability to obtain linear rates of methylation over long
      periods, making this a promising method of high-throughput screening for
      inhibitors.

PMID- 20139416
TI  - Recurrent RNA motifs as probes for studying RNA-protein interactions in the
      ribosome.
AB  - To understand how the nucleotide sequence of ribosomal RNA determines its
      tertiary structure, we developed a new approach for identification of those
      features of rRNA sequence that are responsible for formation of different short-
      and long-range interactions. The approach is based on the co-analysis of several
      examples of a particular recurrent RNA motif. For different cases of the motif,
      we design combinatorial gene libraries in which equivalent nucleotide positions
      are randomized. Through in vivo expression of the designed libraries we select
      those variants that provide for functional ribosomes. Then, analysis of the
      nucleotide sequences of the selected clones would allow us to determine the
      sequence constraints imposed on each case of the motif. The constraints shared by
      all cases are interpreted as providing for the integrity of the motif, while
      those ones specific for individual cases would enable the motif to fit into the
      particular structural context. Here we demonstrate the validity of this approach
      for three examples of the so-called along-groove packing motif found in different
      parts of ribosomal RNA.

PMID- 20139417
TI  - Efficient conditional and promoter-specific in vivo expression of cDNAs of choice
      by taking advantage of recombinase-mediated cassette exchange using FlEx gene
      traps.
AB  - Recombinase-mediated cassette exchange (RMCE) exploits the possibility to
      unidirectionally exchange any genetic material flanked by heterotypic recombinase
      recognition sites (RRS) with target sites in the genome. Due to a limited number
      of available pre-fabricated target sites, RMCE in mouse embryonic stem (ES) cells
      has not been tapped to its full potential to date. Here, we introduce a universal
      system, which allows the targeted insertion of any given transcriptional unit
      into 85 742 previously annotated retroviral conditional gene trap insertions,
      representing 7013 independent genes in mouse ES cells, by RMCE. This system can
      be used to express any given cDNA under the control of endogenous trapped
      promoters in vivo, as well as for the generation of transposon 'launch pads' for
      chromosomal region-specific 'Sleeping Beauty' insertional mutagenesis. Moreover,
      transcription of the gene-of-interest is only activated upon Cre-recombinase
      activity, a feature that adds conditionality to this expression system, which is
      demonstrated in vivo. The use of the RMCE system presented in this work requires
      one single-cloning step followed by one overnight gateway clonase reaction and
      subsequent cassette exchange in ES cells with efficiencies of 40% in average.

PMID- 20139418
TI  - The DNA binding CXC domain of MSL2 is required for faithful targeting the Dosage
      Compensation Complex to the X chromosome.
AB  - Dosage compensation in Drosophila melanogaster involves the selective targeting
      of the male X chromosome by the dosage compensation complex (DCC) and the
      coordinate, approximately 2-fold activation of most genes. The principles that
      allow the DCC to distinguish the X chromosome from the autosomes are not
      understood. Targeting presumably involves DNA sequence elements whose combination
      or enrichment mark the X chromosome. DNA sequences that characterize 'chromosomal
      entry sites' or 'high-affinity sites' may serve such a function. However, to date
      no DNA binding domain that could interpret sequence information has been
      identified within the subunits of the DCC. Early genetic studies suggested that
      MSL1 and MSL2 serve to recognize high-affinity sites (HAS) in vivo, but a direct
      interaction of these DCC subunits with DNA has not been studied. We now show that
      recombinant MSL2, through its CXC domain, directly binds DNA with low nanomolar
      affinity. The DNA binding of MSL2 or of an MSL2-MSL1 complex does not
      discriminate between different sequences in vitro, but in a reporter gene assay
      in vivo, suggesting the existence of an unknown selectivity cofactor. Reporter
      gene assays and localization of GFP-fusion proteins confirm the important
      contribution of the CXC domain for DCC targeting in vivo.

PMID- 20139419
TI  - Modifications in host cell cytoskeleton structure and function mediated by
      intracellular HIV-1 Tat protein are greatly dependent on the second coding exon.
AB  - The human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for
      viral replication because it achieves complete elongation of viral transcripts.
      Tat can be released to the extracellular space and taken up by adjacent cells,
      exerting profound cytoskeleton rearrangements that lead to apoptosis. In
      contrast, intracellular Tat has been described as protector from apoptosis. Tat
      gene is composed by two coding exons that yield a protein of 101 amino acids
      (aa). First exon (1-72aa) is sufficient for viral transcript elongation and
      second exon (73-101 aa) appears to contribute to non-transcriptional functions.
      We observed that Jurkat cells stably expressing intracellular Tat101 showed gene
      expression deregulation 4-fold higher than cells expressing Tat72. Functional
      experiments were performed to evaluate the effect of this deregulation. First, NF
      kappaB-, NF-AT- and Sp1-dependent transcriptional activities were greatly
      enhanced in Jurkat-Tat101, whereas Tat72 induced milder but efficient activation.
      Second, cytoskeleton-related functions as cell morphology, proliferation,
      chemotaxis, polarization and actin polymerization were deeply altered in Jurkat
      Tat101, but not in Jurkat-Tat72. Finally, expression of several cell surface
      receptors was dramatically impaired by intracellular Tat101 but not by Tat72.
      Consequently, these modifications were greatly dependent on Tat second exon and
      they could be related to the anergy observed in HIV-1-infected T cells.

PMID- 20139420
TI  - Structure and DNA binding activity of the mouse condensin hinge domain highlight
      common and diverse features of SMC proteins.
AB  - Structural Maintenance of Chromosomes (SMC) proteins are vital for a wide range
      of processes including chromosome structure and dynamics, gene regulation and DNA
      repair. Eukaryotes have three SMC complexes, consisting of heterodimeric pairs of
      six different SMC proteins along with several specific regulatory subunits. In
      addition to their other functions, all three SMC complexes play distinct roles in
      DNA repair. Cohesin (SMC1-SMC3) is involved in DNA double-strand break repair,
      condensin (SMC2-SMC4) participates in single-strand break (SSB) repair, and the
      SMC5-SMC6 complex functions in various DNA repair pathways. SMC proteins consist
      of N- and C-terminal domains that fold back onto each other to create an ATPase
      'head' domain, connected to a central 'hinge' domain via long coiled-coils. The
      hinge domain mediates dimerization of SMC proteins and binds DNA, but it is not
      clear to what purpose this activity serves. We studied the structure and function
      of the condensin hinge domain from mouse. While the SMC hinge domain structure is
      largely conserved from prokaryotes to eukaryotes, its function seems to have
      diversified throughout the course of evolution. The condensin hinge domain
      preferentially binds single-stranded DNA. We propose that this activity plays a
      role in the SSB repair function of the condensin complex.

PMID- 20139421
TI  - Dual FRET assay for detecting receptor protein interaction with DNA.
AB  - We present here a new assay that is based on the idea of the molecular beacon.
      This assay makes it possible to investigate two proteins interacting with DNA at
      two binding sites that are close to each other. The effectiveness of the test
      depends on the exclusive binding of three DNA fragments in the presence of two
      proteins, and the monitoring of the process depends upon observing the quenching
      of two independent fluorescence donors. As a model we used the components of the
      heterodimeric ecdysteroid receptor proteins ultraspiracle (Usp) and ecdysone
      receptor (EcR) from Drosophila melanogaster and a response element from the
      promoter of the hsp27 gene. The response element consists of two binding sites
      (half-sites) for the DNA binding domains (DBDs). We have shown that protein
      protein interactions mediate cooperative binding of the ecdysteroid receptor DBDs
      to a hsp27(pal) response element. The analysis of the microscopic dissociation
      constants obtained with the DMB led to the conclusion that there was increased
      affinity of UspDBD to the 5' half-site in the presence of EcRDBD when the 3' half
      site was occupied, and increased affinity of EcRDBD to the 3' half-site when the
      5' half-site was occupied.

PMID- 20139422
TI  - Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine
      phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via
      specific domains regulate excitatory synapse formation.
AB  - Synaptic cell adhesion molecules regulate various steps of synapse formation. The
      trans-synaptic adhesion between postsynaptic NGL-3 (for netrin-G ligand-3) and
      presynaptic LAR (for leukocyte antigen-related) regulates excitatory synapse
      formation in a bidirectional manner. However, little is known about the molecular
      details of the NGL-3-LAR adhesion and whether two additional LAR family proteins,
      protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma, also interact with
      NGL-3 and are involved in synapse formation. We report here that the leucine-rich
      repeat (LRR) domain of NGL-3, containing nine LRRs, interacts with the first two
      fibronectin III (FNIII) domains of LAR to induce bidirectional synapse formation.
      Moreover, Gln-96 in the first LRR motif of NGL-3 is critical for LAR binding and
      induction of presynaptic differentiation. PTPdelta and PTPsigma also interact
      with NGL-3 via their first two FNIII domains. These two interactions promote
      synapse formation in a different manner; the PTPsigma-NGL-3 interaction promotes
      synapse formation in a bidirectional manner, whereas the PTPdelta-NGL-3
      interaction instructs only presynaptic differentiation in a unidirectional
      manner. mRNAs encoding LAR family proteins display overlapping and differential
      expression patterns in various brain regions. These results suggest that trans
      synaptic adhesion between NGL-3 and the three LAR family proteins regulates
      excitatory synapse formation in shared and distinct neural circuits.

PMID- 20139423
TI  - Snf1 dependence of peroxisomal gene expression is mediated by Adr1.
AB  - Eukaryotes utilize fatty acids by beta-oxidation, which occurs in the
      mitochondria and peroxisomes in higher organisms and in the peroxisomes in yeast.
      The AMP-activated protein kinase regulates this process in mammalian cells, and
      its homolog Snf1, together with the transcription factors Adr1, Oaf1, and Pip2,
      regulates peroxisome proliferation and beta-oxidation in yeast. A constitutive
      allele of Adr1 (Adr1(c)) lacking the glucose- and Snf1-regulated phosphorylation
      substrate Ser-230 was found to be Snf1-independent for regulation of peroxisomal
      genes. In addition, it could compensate for and even suppress the requirement for
      Oaf1 or Pip2 for gene induction. Peroxisomal genes were found to be regulated by
      oleate in the presence of glucose, as long as Adr1(c) was expressed, suggesting
      that the Oaf1/Pip2 heterodimer is Snf1-independent. Consistent with this
      observation, Oaf1 binding to promoters in the presence of oleate was not reduced
      in a snf1Delta strain. Exploring the mechanism by which Adr1(c) permits Snf1
      independent peroxisomal gene induction, we found that strength of promoter
      binding did not correlate with transcription, suggesting that stable binding is
      not a prerequisite for enhanced transcription. Instead, enhanced transcriptional
      activation and suppression of Oaf1, Pip2, and Snf1 by Adr1(c) may be related to
      the ability of Adr1(c) to suppress the requirement for and enhance the
      recruitment of transcriptional coactivators in a promoter- and growth medium
      dependent manner.

PMID- 20139424
TI  - A nucleosome surface formed by histone H4, H2A, and H3 residues is needed for
      proper histone H3 Lys36 methylation, histone acetylation, and repression of
      cryptic transcription.
AB  - Set2-mediated H3 Lys(36) methylation is a histone modification that has been
      demonstrated to function in transcriptional elongation by recruiting the Rpd3S
      histone deacetylase complex to repress intragenic cryptic transcription.
      Recently, we identified a trans-histone pathway in which the interaction between
      the N terminus of Set2 and histone H4 Lys(44) is needed to mediate trans-histone
      H3 Lys(36) di- and trimethylation. In the current study, we demonstrate that
      mutation of the lysine 44 residue in histone H4 or the Set2 mutant lacking the
      histone H4 interaction motif leads to intragenic cryptic transcripts, indicating
      that the Set2 and histone H4 interaction is important to repress intragenic
      cryptic transcription. We also determine that histone H2A residues (Leu(116) and
      Leu(117)), which are in close proximity to histone H4 Lys(44), are needed for
      proper trans-histone H3 Lys(36) methylation. Similar to H4 Lys(44) mutants,
      histone H2A Leu(116) and Leu(117) mutations exhibited decreased H3 Lys(36) di-
      and trimethylation, increased histone H4 acetylation, increased resistance to 6
      azauracil, and cryptic transcription. Interestingly, the combined histone H4
      Lys(44) and H2A mutations have more severe methylation defects and increased H4
      acetylation levels. Furthermore, we identify that additional histone H2A and H3
      core residues are also needed for H3 Lys(36) di- and trimethylation. Overall, our
      results show and suggest that multiple H4, H2A, and H3 residues contribute to and
      form a Set2 docking/recognition site on the nucleosomal surface so that proper
      Set2-mediated H3 Lys(36) di- and trimethylation, histone acetylation, and
      transcriptional elongation can occur.

PMID- 20139425
TI  - Sodium selenite improves the in vitro follicular development by reducing the
      reactive oxygen species level and increasing the total antioxidant capacity and
      glutathione peroxide activity.
AB  - BACKGROUND: The aim of this study was to investigate the effect of sodium
      selenite (SS) on reactive oxygen species (ROS) production, total antioxidant
      capacity (TAC) and glutathione peroxide (GPx) activity of cultured pre-antral
      follicles derived from vitrified and non-vitrified ovarian tissue. METHODS:
      Immature mouse ovaries were vitrified, and mechanically isolated pre-antral
      follicles from vitrified and non-vitrified samples were cultured in TCM 199
      medium supplemented with different concentrations (0, 5 and 10 ng/ml) of SS.
      Follicular, oocyte and embryo development was assessed. In parallel, ROS, TAC and
      GPx levels were analyzed after 0, 12, 24, 48, 72 and 96 h of culture. RESULTS:
      Development rates of follicles, oocytes and embryos were significantly higher in
      SS-supplemented groups (P < 0.005). ROS production was increased, and TAC levels
      and GPx activities were decreased after 24 h of culture of pre-antral follicles
      in vitrified and non-vitrified groups, whereas in the presence of SS, ROS
      production was decreased and TAC levels and selenium-dependent GPx-specific
      activities were increased after 96 h of culture. Vitrified and non-vitrified
      samples responded in a similar manner. CONCLUSION: SS caused an increase in
      follicular TAC level and GPx activity and a decrease in ROS level, thus improving
      the in vitro development of follicles.

PMID- 20139426
TI  - A case of Kallmann syndrome carrying a missense mutation in alternatively spliced
      exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor
      receptor 1.
AB  - Fibroblast growth factor receptor 1 (FGFR1) is one of the causative genes for
      Kallmann syndrome (KS), which is characterized by isolated hypogonadotropic
      hypogonadism with anosmia/hyposmia. The third immunoglobulin-like domain (D3) of
      FGFR1 has the isoforms FGFR1-IIIb and FGFR1-IIIc, which are generated by
      alternative splicing of exons 8A and 8B, respectively. To date, the only
      mutations to have been identified in D3 of FGFR1 are in exon 8B. We performed
      mutation analysis of FGFR1 in a 23-year-old female patient with KS and found a
      missense mutation (c.1072C>T) in exon 8A of FGFR1. The c.1072C>T mutation was not
      detected in her family members or in 220 normal Japanese and 100 Caucasian female
      controls. No mutation in other KS genes, KS 1, prokineticin-2, prokineticin
      receptor-2 and FGF-8 was detected in the affected patient or in her family
      members. Therefore, this is the first case of KS carrying a de novo missense
      mutation in FGFR1 exon 8A, suggesting that isoform FGFR1-IIIb, as well as isoform
      FGFR1-IIIc, plays a crucial role in the pathogenesis of KS.

PMID- 20139427
TI  - Effects of oral and vaginal administration of levonorgestrel emergency
      contraception on markers of endometrial receptivity.
AB  - BACKGROUND: The standard regimen of the levonorgestrel-only pill (1.5 mg either
      in a single dose or in a dose of 0.75 mg twice, 12 h apart) administered orally
      for emergency contraception (EC) has been shown to have no effect on endometrial
      development and markers of endometrial receptivity. We aimed to explore whether
      repeated oral and single vaginal administration of levonorgestrel affect the
      endometrium and thus potentially increase the EC efficacy, compared with the
      standard regimen. METHODS: Endometrial biopsies were taken from non-smoking,
      healthy women with proven fertility on cycle days LH + 6 to LH + 8 in control and
      levonorgestrel treatment cycles (each woman serving as her own control).
      Levonorgestrel was administered either orally (0.75 mg x 4, at 24 h intervals on
      LH + 1 to LH + 4; n = 8) or vaginally (a single dose of 1.5 mg on LH + 2; n = 7).
      Immunohistochemistry and real-time RT-PCR was performed to compare the levels of
      protein and mRNA for sex steroid receptors, interleukin-1beta, leukaemia
      inhibitory factor (LIF), vascular endothelial growth factor, cyclooxygenase-2,
      tumour necrosis factor-alpha, integrin alpha(v)beta(3) and mucin 1 in endometrial
      cells. RESULTS: Following the repeated oral treatment, the immunoreactivity of
      both progesterone receptor (PR)-A and PR-B declined in glandular epithelium (P =
      0.03 and P = 0.02, respectively), whereas stromal immunoreactivity and mRNA
      expression of LIF increased compared with control (P < 0.001 and P = 0.03,
      respectively). However, vaginal levonorgestrel did not cause any significant
      endometrial changes. CONCLUSIONS: The two regimens of levonorgestrel caused
      either only minor or no alterations in markers of endometrial receptivity. New
      agents targeting the endometrial development should be explored in order to
      increase EC efficacy.

PMID- 20139428
TI  - Parental infertility and developmental coordination disorder in children.
AB  - BACKGROUND: It has previously been reported that children born after infertility
      treatment had a slight delay in early motor milestones. In this study, we
      examined whether children of infertile couples with or without infertility
      treatment had a higher risk of developmental coordination disorder (DCD).
      METHODS: We used data on parental infertility and DCD among 23 167 singletons
      from the Danish National Birth Cohort (1996-2002). Data on time to pregnancy
      (TTP) and infertility treatment were collected early in pregnancy. Data on DCD in
      children were collected using the Developmental Coordination Disorder
      Questionnaire, filled in by the mothers during follow-up when the children were 7
      years old. We used the recommended cut-off for the age group to classify
      children. RESULTS: Compared with children born of fertile couples, children
      conceived after a waiting TTP of longer than 12 months had a slightly higher risk
      of DCD [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.03-1.77], but the
      estimated OR was not significant in children born after infertility treatment (OR
      1.19, 95% CI 0.86-1.66). None of the individual treatment procedures was
      significantly associated with a higher risk of DCD. Children of parents who had
      not planned their pregnancy showed no elevated risk. CONCLUSIONS: Our findings
      are overall reassuring, although it is possible that low fecundity may be
      associated with a modestly increased risk of DCD.

PMID- 20139429
TI  - Sperm DNA: organization, protection and vulnerability: from basic science to
      clinical applications--a position report.
AB  - This article reports the results of the most recent in a series of EHSRE
      workshops designed to synthesize the current state of the field in Andrology and
      provide recommendations for future work (for details see Appendix). Its focus is
      on methods for detecting sperm DNA damage and potential application of new
      knowledge about sperm chromatin organization, vulnerability and repair to improve
      the diagnosis and treatment of clinical infertility associated with that damage.
      Equally important is the use and reliability of these tests to identify the
      extent to which environmental contaminants or pharmaceutical agents may
      contribute to the incidence of sperm DNA damage and male fertility problems. A
      working group (for workshop details, see Appendix) under the auspices of ESHRE
      met in May 2009 to assess the current knowledgebase and suggest future basic and
      clinical research directions. This document presents a synthesis of the working
      group's understanding of the recent literature and collective discussions on the
      current state of knowledge of sperm chromatin structure and function during
      fertilization. It highlights the biological, assay and clinical uncertainties
      that require further research and ends with a series of 5 key recommendations.

PMID- 20139430
TI  - The non-ergot derived dopamine agonist quinagolide in prevention of early ovarian
      hyperstimulation syndrome in IVF patients: a randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) seems to be induced by the
      ovarian release of vascular endothelial growth factor (VEGF), which increases
      vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation
      and thereby decrease vascular permeability. METHODS: A randomized, double-blind,
      placebo-controlled, multicentre study assessing three oral doses (50, 100, 200
      microg/day) of the non-ergot derived dopamine agonist quinagolide started on the
      day of human chorionic gonadotrophin (hCG) and continued for 17-21 days without
      dose-titration in comparison to placebo in preventing moderate/severe early OHSS
      (onset < or =9 days after hCG administration) in 182 IVF patients with > or =20
      but less than 30 follicles > or =10 mm. RESULTS: The incidence of moderate/severe
      early OHSS was 23% (12/53) in the placebo group and 12% (6/51), 13% (7/52) and 4%
      (1/26) in the quinagolide 50, 100 and 200 microg/day groups, respectively. The
      moderate/severe early OHSS rate was significantly lower with all quinagolide
      groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09-0.81)]. The
      incidence of ultrasound evidence of ascites among patients with no clinical
      pregnancy was significantly reduced from 31% (8/26) with placebo to 11% (8/70)
      with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10-0.88)], although
      there was no difference for those with clinical pregnancy. Quinagolide did not
      have a detrimental effect on pregnancy or live birth rates. The incidence of
      gastrointestinal and central nervous system adverse events increased with
      increasing doses of quinagolide. CONCLUSIONS: Quinagolide appears to prevent
      moderate/severe early OHSS while not affecting treatment outcome. The effect is
      more marked in patients who did not achieve a clinical pregnancy. Quinagolide
      administered in high doses without dose-titration is associated with poor
      tolerability. ClinicalTrials.gov Identifier: NCT00329693.

PMID- 20139431
TI  - Trends in delivery and neonatal outcome after in vitro fertilization in Sweden:
      data for 25 years.
AB  - BACKGROUND: Marked changes have occurred in in vitro fertilization (IVF)
      methodology during the past 25 years but also in characteristics of couples
      undergoing treatment. METHODS: This study was based on 27 386 women undergoing
      IVF treatment from 1982 to 2006 and giving birth to 31 850 infants. Outcomes of
      deliveries were studied using Swedish health registers. Comparisons were made
      with all deliveries in the population (n = 2 603 601). Adjusted odds ratios were
      calculated when important changes in background rates had occurred. RESULTS:
      There was a substantial increase in the use of intracytoplasmatic sperm injection
      (ICSI) and the transfer of cryopreserved embryos. Among all ICSI cases, the
      proportion using epididymal or testicular sperm varied between 5 and 10%.
      Maternal characteristics changed during the observation period but the median age
      remained relatively constant in spite of the increasing maternal age in the
      population. There was a decline in the rate of some maternal pregnancy diagnoses
      (notably pre-eclampsia, premature rupture of membranes) and some neonatal
      diagnoses (notably preterm births, low birthweight, cerebral hemorrhage,
      respiratory diagnoses, use of continuous positive airway pressure and mechanical
      ventilation, sepsis/pneumonia). Up till 1992, the twinning rate increased to a
      maximum of about 30% and then declined to 5% towards the end of the period
      whereas higher order multiples nearly disappeared. The total rate of infants with
      congenital malformations changed only little. CONCLUSIONS: The decrease in
      unwanted outcomes can, to a large extent, be explained by the reduced rate of
      multiple births but was seen also among singletons. Other explanations can be
      sought in changes in the characteristics of patients undergoing IVF.

PMID- 20139432
TI  - Information for decision making: lot quality assurance sampling in the spotlight.

PMID- 20139433
TI  - LQAS: User Beware.
AB  - BACKGROUND: Researchers around the world are using Lot Quality Assurance Sampling
      (LQAS) techniques to assess public health parameters and evaluate program
      outcomes. In this paper, we report that there are actually two methods being
      called LQAS in the world today, and that one of them is badly flawed. METHODS:
      This paper reviews fundamental LQAS design principles, and compares and contrasts
      the two LQAS methods. We raise four concerns with the simply-written, freely
      downloadable training materials associated with the second method. RESULTS: The
      first method is founded on sound statistical principles and is carefully designed
      to protect the vulnerable populations that it studies. The language used in the
      training materials for the second method is simple, but not at all clear, so the
      second method sounds very much like the first. On close inspection, however, the
      second method is found to promote study designs that are biased in favor of
      finding programmatic or intervention success, and therefore biased against the
      interests of the population being studied. CONCLUSION: We outline several
      recommendations, and issue a call for a new high standard of clarity and face
      validity for those who design, conduct, and report LQAS studies.

PMID- 20139434
TI  - Commentary: Understanding practical lot quality assurance sampling.

PMID- 20139435
TI  - An assessment of Lot Quality Assurance Sampling to evaluate malaria outcome
      indicators: extending malaria indicator surveys.
AB  - BACKGROUND: Large investments and increased global prioritization of malaria
      prevention and treatment have resulted in greater emphasis on programme
      monitoring and evaluation (M&E) in many countries. Many countries currently use
      large multistage cluster sample surveys to monitor malaria outcome indicators on
      a regional and national level. However, these surveys often mask local-level
      variability important to programme management. Lot Quality Assurance Sampling
      (LQAS) has played a valuable role for local-level programme M&E. If incorporated
      into these larger surveys, it would provide a comprehensive M&E plan at little,
      if any, extra cost. METHODS: The Mozambique Ministry of Health conducted a
      Malaria Indicator Survey (MIS) in June and July 2007. We applied LQAS
      classification rules to the 345 sampled enumeration areas to demonstrate
      identifying high- and low-performing areas with respect to two malaria program
      indicators-'household possession of any bednet' and 'household possession of any
      insecticide-treated bednet (ITN)'. RESULTS: As shown by the MIS, no province in
      Mozambique achieved the 70% coverage target for household possession of bednets
      or ITNs. By applying LQAS classification rules to the data, we identify 266 of
      the 345 enumeration areas as having bednet coverage severely below the 70%
      target. An additional 73 were identified with low ITN coverage. CONCLUSIONS: This
      article demonstrates the feasibility of integrating LQAS into multistage cluster
      sampling surveys and using these results to support a comprehensive national,
      regional and local programme M&E system. Furthermore, in the recommendations we
      outlined how to integrate the Large Country-LQAS design into macro-surveys while
      still obtaining results available through current sampling practices.

PMID- 20139436
TI  - Action towards healthy living--for all.

PMID- 20139437
TI  - Atrial fibrillation and circulating endothelial progenitor cells.

PMID- 20139438
TI  - Research into practice: 10 years of international public health partnership
      between the UK and Swaziland.
AB  - BACKGROUND: There is increasing interest in global health partnerships. However,
      evidence of benefit remains weak. We report on the impact of a 10-year public
      health partnership between the UK and Swaziland. Swaziland has the highest rates
      of TB and HIV in the world. Health services are being overwhelmed and patients
      suffer the cost and inconvenience of centralized services. Our international
      health partnership was set up to promote the translation of public health
      research into practice. METHODS: The partnership is based on six principles:
      sustainability; robust measurement; evidence-based practice; patient-centred
      improvement; systems approach and researchers as implementers. Based on rigorous
      health needs assessments and informed by international evidence, we have achieved
      a number of successful changes. RESULTS: The partnership has been successful in
      the development of a community TB service; a chronic disease programme for
      epilepsy; implementation of guidelines; implementation of ART programmes; nurse
      led community ART clinics; innovations to improve follow-up and expert patients.
      CONCLUSION: Global inequalities are increasing rapidly and international
      partnership has an important role in tackling this threat. Partnerships should be
      based on sustainable, long-term links with a strong foundation of trust and
      mutual support. Effective leadership, good communication, clinical engagement and
      interagency collaboration are pre-requisites for the successful implementation of
      success.

PMID- 20139439
TI  - Predictors of exercise capacity and symptoms in severe aortic stenosis.
AB  - AIMS: This study investigated the association between invasive and non-invasive
      estimates of left ventricular (LV) filling pressure and exercise capacity, in
      order to find new potential candidates for risk markers in severe aortic valve
      stenosis (AS). METHODS AND RESULTS: Twenty-nine patients with AS, aortic valve
      area (AVA) < 1 cm(2), performed a symptom-limited multistage supine bicycle
      exercise test. Immediately before the exercise test, the pulmonary capillary
      wedge pressure (PCWP), Doppler index for LV filling (E/e'), and left atrial (LA)
      volume were measured. Symptomatic status was determined by senior staff doctors
      blinded to the results of this study. All patients terminated the exercise test
      because of dyspnoea. There were no significant differences in AVA between
      asymptomatic patients (n = 9) and symptomatic patients (n = 20), and AVA did not
      correlate with exercise capacity (r = -0.16, P = NS). In contrast, PCWP, LA
      volume, and E/e' were significantly increased in the symptomatic group and they
      all correlated with exercise capacity (r = -0.66, -0.75, and -0.62, respectively,
      P < 0.001). Receiver operating characteristic curve analysis confirmed that PCWP,
      LA volume index, and E/e' all provided incremental information [area under the
      curve (AUC) = 0.90, 0.92, and 0.90, respectively, P < 0.05] over AVA index (AUC =
      0.66, NS) in predicting symptomatic status. CONCLUSION: PCWP, LA volume, or E/e'
      is closely related to exercise capacity and symptomatic status, and may therefore
      be important markers of disease severity in AS. Clinical Trials.gov Identifier:
      NCT00252317 (http://clinicaltrials.gov/ct2/results?term=NCT00252317).

PMID- 20139440
TI  - Automated border detection in three-dimensional echocardiography: principles and
      promises.
AB  - Several automated border detection approaches for three-dimensional
      echocardiography have been developed in recent years, allowing quantification of
      a range of clinically important parameters. In this review, the background and
      principles of these approaches and the different classes of methods are described
      from a practical perspective, as well as the research trends to achieve a robust
      method.

PMID- 20139441
TI  - Impact of high altitude on echocardiographically determined cardiac morphology
      and function in patients with coronary artery disease and healthy controls.
AB  - AIMS: To evaluate the impact of high altitude on cardiac morphology and function
      in patients with coronary artery disease (CAD) and healthy controls. METHODS AND
      RESULTS: Eight patients with a history of acute myocardial infarction [53 +/- 8
      years, left ventricular (LV) ejection fraction 54 +/- 6%] and a low risk score
      were compared with seven healthy controls (41 +/- 16 years) during the Dutch
      Heart Expedition 2007 at the Aconcagua (6960 m) in Argentina. An exercise test
      and echocardiography were performed at sea level and at base camp (4200 m). In
      the apical four-chamber view, right ventricular (RV) diameter, tricuspid annular
      plane systolic excursion (TAPSE), early transmitral inflow peak velocity (E),
      atrial transmitral inflow peak velocity (A), and peak tissue velocity during
      early diastole (E') were obtained. Changes in global LV function and wall motion
      score index (WMSI) were used as markers of ischaemia. There were no significant
      differences in individual global LV function and WMSI at high altitude compared
      with sea level in both groups. A significant increase in RV diameter was observed
      in the patient group at 4200 m compared with sea level and a trend towards the
      same result in the control group. A decrease in TAPSE was observed. Measurements
      of the E' showed a significant decrease in the LV septum and lateral wall at high
      altitude compared with sea level in both groups. CONCLUSION: Symptoms and
      echocardiographic signs of myocardial ischaemia were absent in low-risk patients
      with a history of CAD during and after exercise up to an altitude of 4200 m.
      Patients and healthy controls showed comparable changes at high altitude compared
      with sea level with an increase in RV diameter, a decrease in TAPSE, and
      decreased E' as early signs of pulmonary hypertension and LV diastolic
      dysfunction. As these alterations are most likely physiological adaptation to
      high altitude, the results seem to affirm current guidelines. The safety of
      expanding previous recommendations to patients with low-risk CAD to an altitude
      ascent of 4200 m requires confirmation in a larger study with appropriately
      defined clinical endpoints.

PMID- 20139443
TI  - The XBP-Bax1 helicase-nuclease complex unwinds and cleaves DNA: implications for
      eukaryal and archaeal nucleotide excision repair.
AB  - XPB helicase is an integral part of transcription factor TFIIH, required for both
      transcription initiation and nucleotide excision repair (NER). Along with the XPD
      helicase, XPB plays a crucial but only partly understood role in defining and
      extending the DNA repair bubble around lesions in NER. Archaea encode clear
      homologues of XPB and XPD, and structural studies of these proteins have yielded
      key insights relevant to the eukaryal system. Here we show that archaeal XPB
      functions with a structure-specific nuclease, Bax1, as a helicase-nuclease
      machine that unwinds and cleaves model NER substrates. DNA bubbles are extended
      by XPB and cleaved by Bax1 at a position equivalent to that cut by the XPG
      nuclease in eukaryal NER. The helicase activity of archaeal XPB is dependent on
      the conserved Thumb domain, which may act as the helix breaker. The N-terminal
      damage recognition domain of XPB is shown to be crucial for XPB-Bax1 activity and
      may be unique to the archaea. These findings have implications for the role of
      XPB in both archaeal and eukaryal NER and for the evolution of the NER pathway.
      XPB is shown to be a very limited helicase that can act on small DNA bubbles and
      open a defined region of the DNA duplex. The specialized functions of the
      accessory domains of XPB are now more clearly delineated. This is also the first
      direct demonstration of a repair function for archaeal XPB and suggests strongly
      that the role of XPB in transcription occurred later in evolution than that in
      repair.

PMID- 20139445
TI  - The involuntary capture of attention by novel feature pairings: a study of voice
      location integration in auditory sensory memory.
AB  - Past researchers of the integration of information in memory have typically
      required participants to attend to and/or commit to memory the stimuli conveying
      distinct features, rendering difficult the examination of whether the maintenance
      of the feature pairings can occur involuntarily. To address this issue, the
      integration of voice and location information in auditory sensory memory was
      measured using a cross-modal oddball task, in which task-irrelevant auditory
      deviants are known to capture attention in an involuntary fashion. Participants
      categorized visual digits presented shortly after to-be-ignored sounds. These
      sounds consisted in the same phoneme played simultaneously in both ears but in
      different voices (female in one ear, male in the other). On most trials, the
      pairing of voice to location was constant (standard sound). On rare and
      unpredictable trials, the voices swapped locations (deviant sound). In line with
      past work on attention capture by auditory novelty, the participants were
      significantly slower to judge the visual digits following the deviant sound,
      indicating the involuntary encoding of the links between voice and location in
      auditory memory. These results suggest that voices and locations are integrated
      in memory and that this binding occurs in conditions in which participants do not
      intend to commit any information to memory.

PMID- 20139446
TI  - Eye movements in active visual search: a computable phenomenological model.
AB  - We present a computational model and corresponding computer simulations that
      mimic phenomenologically the eye movement trajectories observed in a conjunctive
      visual search task. The element of randomness is captured in the model through a
      Monte Carlo selection of a particular eye movement based on its probability,
      which depends on three factors, adjusted to match to the observed saccade
      amplitude distribution, forward bias in consecutive saccades, and return rates.
      Memory is assumed to operate through tagging of objects already recognized as
      nontargets, which, in turn, requires their processing within the attentional area
      of conspicuity (AC). That AC is adjusted so that computer simulations optimally
      reproduce the distribution of the number of saccades, the failure rate for
      capturing the target, and the return rate to previously inspected locations. For
      their viability, computer simulations critically depend on memory's being long
      ranged. In turn, the simulations confirm the formation of circulating or
      spiraling patterns in the observed eye trajectories. We also relate consistently
      the average number of saccades per trial to the saccade amplitude distribution by
      modeling analytically the combined roles of the AC in attention and memory. The
      full Supplemental Appendix A for this article may be downloaded from
      http://app.psychonomic-journals.org/content/supplemental.

PMID- 20139447
TI  - Executive working memory load does not compromise perceptual processing during
      visual search: evidence from additive factors analysis.
AB  - Executive working memory (WM) load reduces the efficiency of visual search, but
      the mechanisms by which this occurs are not fully known. In the present study, we
      assessed the effect of executive load on perceptual processing during search.
      Participants performed a serial oculomotor search task, looking for a circle
      target among gapped-circle distractors. The participants performed the task under
      high and low executive WM load, and the visual quality (Experiment 1) or
      discriminability of targets and distractors (Experiment 2) was manipulated across
      trials. By the logic of the additive factors method (Sternberg, 1969, 1998), if
      WM load compromises the quality of perceptual processing during visual search,
      manipulations of WM load and perceptual processing difficulty should produce
      nonadditive effects. Contrary to this prediction, the effects of WM load and
      perceptual difficulty were additive. The results imply that executive WM load
      does not degrade perceptual analysis during visual search.

PMID- 20139448
TI  - The attentional blink and lag 1 sparing are nonspatial.
AB  - The attentional blink (AB) refers to the finding that the perception of the
      second of two targets (T2) is impaired when presented in close temporal proximity
      to the first target (T1). An exception to this deficit occurs when T2 immediately
      follows T1, an effect referred to as lag 1 sparing. So far, it has been unclear
      whether the AB is location specific or nonspatial in nature. Most demonstrations
      of an AB across different locations have shown an absence of lag 1 sparing, due
      to accompanying spatial switch costs. This means that the AB pattern itself may
      be explained through such switch costs. In this study, to minimize spatial switch
      costs, attention was made to move continuously across multiple locations by aid
      of a cue. An AB across different locations was found, including lag 1 sparing. We
      conclude that the AB and lag 1 sparing are not tied to a location but represent a
      central deficit, in line with current theory.

PMID- 20139449
TI  - What is top-down about contingent capture?
AB  - In the present study, we explored the mechanisms involved in the contingent
      capture phenomenon, using a variant of the classic precuing paradigm of Folk,
      Remington, and Johnston (1992). Rather than keeping the target fixed over a whole
      block of trials (as has traditionally been done with contingent capture
      experiments), we encouraged participants to adopt a top-down set before each
      trial. If top-down attentional set determines which property captures attention,
      as is claimed by the contingent capture hypothesis, one would expect that only
      properties that match the top-down set would capture attention. We showed that
      even though participants knew what the target would be on the upcoming trial,
      both relevant and irrelevant properties captured attention (Experiment 1). An
      intertrial analysis (Experiments 1 and 2) showed that previous contingent capture
      findings may, to a large extent, be explained by intertrial priming. In addition,
      when participants were further forced into adopting the required top-down set
      (Experiments 3 and 4), irrelevant cues were suppressed, suggesting that top-down
      control might operate through disengagement of attention from the location of a
      property that does not match top-down goals. The present findings suggest that
      top-down control and intertrial priming make their own distinct contributions to
      the contingent capture phenomenon.

PMID- 20139450
TI  - Variations in the magnitude of attentional capture: testing a two-process model.
AB  - Although large variations in the magnitude of attentional capture have been
      evidenced across a wide range of studies and paradigms (see Burnham, 2007, for a
      review), the nature of these variations is unclear. In the present study, we used
      a modified spatial cuing task to address two related issues. In the first
      experiment, we explored the hypothesis that the magnitude of attentional capture
      varies systematically as a function of cue-target similarity. Targets of a
      particular color were preceded by uninformative peripheral cues carrying varying
      percentages of the target color. As was predicted, the magnitude of attentional
      capture varied directly with the similarity between cue and target. In the second
      experiment, we explored whether these similarity effects reflect a mixture of
      trials on which attention is fully captured and trials on which attention is not
      captured at all (i.e., a two-process model). A mixture analysis conducted on
      obtained reaction time distributions proved inconsistent with a two-process
      model.

PMID- 20139451
TI  - Selective attention and subjective confidence calibration.
AB  - In the present experiments, failures of selective visual attention were invoked
      using the B. A. Eriksen and C. W. Eriksen (1974) flanker task. On each trial, a
      three-letter stimulus array was flashed briefly, followed by a mask. The identity
      of the two flanking letters was response congruent, neutral, or incongruent with
      the identity of the middle target letter. On half of the trials, confidence
      ratings were obtained after each response. In the first three experiments,
      participants were highly overconfident in the accuracy of their responding to
      incongruent flanker stimulus arrays. In a final experiment, presenting a
      prestimulus target location cue greatly reduced both selective attention failure
      and overconfidence. The findings demonstrate that participants are often unaware
      of such selective attention failures and provide support for the notion that, in
      these cases, decisional processing is driven largely by the identities of the
      incongruent flankers. In addition, responding was invariably slower and sometimes
      more accurate when confidence was required than when it was not required,
      demonstrating that the need to provide posttrial confidence reports can affect
      decisional processing. Moreover, there was some evidence that the presence of
      neutral contextual flanking information can slow responding, suggesting that such
      nondiagnostic information can, indeed, contribute to decisional processing.

PMID- 20139452
TI  - Time course of visual attention with emotional faces.
AB  - When a briefly presented and then masked visual object is identified, it impairs
      the identification of the second target for several hundred milliseconds. This
      phenomenon is known as attentional blink or attentional dwell time. The present
      study is an attempt to investigate the role of salient emotional information in
      shifts of covert visual attention over time. Two experiments were conducted using
      the dwell time paradigm, in which two successive targets are presented at
      different locations with a variable stimulus onset asynchrony (SOA). In the first
      experiment, real emotional faces (happy/sad) were presented as the first target,
      and letters (L/T) were presented as the second target. The order of stimulus
      presentation was reversed in the second experiment. In the first experiment,
      identification of the letters preceded by happy faces showed better performance
      than did those preceded by sad faces at SOAs less than 200 msec. Similarly, happy
      faces were identified better than sad faces were at short SOAs in Experiment 2.
      The results show that the time course of visual attention is dependent on
      emotional content of the stimuli. The findings indicate that happy faces are
      associated with distributed attention or broad scope of attention and require
      fewer attentional resources than do sad faces.

PMID- 20139453
TI  - Audiovisual bounce-inducing effect: when sound congruence affects grouping in
      vision.
AB  - Two disks moving from opposite points in space, overlapping, and stopping at one
      another's starting point can be seen as either bouncing off one another or
      streaming through one another. With silent displays, observers report streaming,
      whereas, if a sound is played when the disks are in the overlap region, observers
      report bouncing. The change in perception is thought to be modulated by a lack of
      attention that inhibits the integration of the motion signal when disks overlap
      and by the sound that increases the congruence of the display, in comparison with
      a real elastic bounce. Here, we accompanied the disks' motion with either a
      bounce-congruent sound (a billiard ball) or with bounce-incongruent sounds (a
      water drop, a firework). When the sound was switched on 200 msec before the
      disks' overlap, (1) all the audiovisual displays induced more bounce responses
      than did the silent display, but (2) the bounce-congruent sound induced more
      bounce responses than did the bounce-incongruent sounds. However, when the sound
      was switched on at the disks' overlap, only the first result was observed. These
      results highlight both the role of attention and that of sound congruence.

PMID- 20139454
TI  - Combined effects of perceptual grouping cues on object representation: evidence
      from motion-induced blindness.
AB  - We investigated the combined effects of perceptual grouping cues (proximity and
      contour closure/proximity and orientation similarity) on object representation,
      using motion-induced blindness, a phenomenon in which salient visual stimuli
      perceptually disappear when surrounded by moving patterns. We presented as visual
      targets two stimuli in which a solid square was embedded in an outlined square.
      Participants reported whether the targets disappeared independently or
      simultaneously. The results showed that a relatively high proximity cue (with a
      0.2-deg separation between the targets) modulated the perceptions of the
      independent or simultaneous disappearances of targets, regardless of other
      grouping cues. The contour closure cue modulated these disappearances in the 0.4-
      to 0.8-deg separations. Finally, the orientation similarity cue began to modulate
      these disappearances in the 0.6- to 0.8-deg separations. We suggest that the
      separation between the visual stimuli modulates the combined effects of
      perceptual grouping cues on complete object representation.

PMID- 20139455
TI  - Unmasking the standing wave of invisibility: an account in terms of object
      mediated representational updating.
AB  - A central bar presented in counterphase with two flanking bars creates the
      perception of only two bars, instead of three, flickering (standing wave of
      invisibility illusion). Current explanations of this illusion highlight the
      importance of local interactions between the central bar and the flankers as a
      reason for the invisibility of the central bar. In three experiments, we show
      that the reduction in visibility of the central bar occurs even when the flankers
      are spatially separated from the central bar. Thus local mechanisms-low-level
      lateral inhibition or border-ownership competition-do not suffice to account for
      the decreased visibility. Furthermore, the reduced visibility of the central bar
      is accompanied by the perception of the flankers in apparent motion at all
      separations. We suggest an account of the standing wave phenomenon in terms of
      object updating: The representation of the central bar is updated with the
      representation of the flankers leaving the perception of just the flankers moving
      across space. The stimuli for the key conditions from this study, in QuickTime
      format, may be down loaded from http://app.psychonomic
      journals.org/content/supplemental.

PMID- 20139456
TI  - Where do we look when we count? The role of eye movements in enumeration.
AB  - Two experiments addressed the coupling between eye movements and the cognitive
      processes underlying enumeration. Experiment 1 compared eye movements in a
      counting task with those in a "look" task, in which subjects were told to look at
      each dot in a pattern once and only once. Experiment 2 presented the same dot
      patterns to every subject twice, to measure the consistency with which dots were
      fixated between and within subjects. In both experiments, the number of fixations
      increased linearly with the number of objects to be enumerated, consistent with
      tight coupling between eye movements and enumeration. However, analyses of
      fixation locations showed that subjects tended to look at dots in dense, central
      regions of the display and tended not to look at dots in sparse, peripheral
      regions of the display, suggesting a looser coupling between eye movements and
      enumeration. Thus, the eyes do not mirror the enumeration process very directly.

PMID- 20139457
TI  - The role of higher order image statistics in masking scene gist recognition.
AB  - In the present article, we investigated whether higher order image statistics,
      which are known to be carried by the Fourier phase spectrum, are sufficient to
      affect scene gist recognition. In Experiment 1, we compared the scene gist
      masking strength of four masking image types that varied in their degrees of
      second- and higher order relationships: normal scene images, scene textures,
      phase-randomized scene images, and white noise. Masking effects were the largest
      for masking images that possessed significant higher order image statistics
      (scene images and scene textures) as compared with masking images that did not
      (phase-randomized scenes and white noise), with scene image masks yielding the
      largest masking effects. In a control study, we eliminated all differences in the
      second-order statistics of the masks, while maintaining differences in their
      higher order statistics by comparing masking by scene textures rather than by
      their phase-randomized versions, and showed that the former produced
      significantly stronger gist masking. Experiments 2 and 3 were designed to test
      whether conceptual masking could account for the differences in the strength of
      the scene texture and phase-randomized masks used in Experiment 1, and revealed
      that the recognizability of scene texture masks explained just 1% of their
      masking variance. Together, the results suggest that (1) masks containing the
      higher order statistical structure of scenes are more effective at masking scene
      gist processing than are masks lacking such structure, and (2) much of the
      disruption of scene gist recognition that one might be tempted to attribute to
      conceptual masking is due to spatial masking.

PMID- 20139458
TI  - Vertical position as a cue to pictorial depth: height in the picture plane versus
      distance to the horizon.
AB  - Two often cited but frequently confused pictorial cues to perceived depth are
      height in the picture plane (HPP) and distance to the horizon (DH). We report two
      psychophysical experiments that disentangled their influence on perception of
      relative depth in pictures of the interior of a schematic room. Experiment 1
      showed that when HPP and DH varied independently with both a ceiling and a floor
      plane visible in the picture, DH alone determined judgments of relative depth;
      HPP was irrelevant. Experiment 2 studied relative depth perception in single
      plane displays (floor only or ceiling only) in which the horizon either was not
      visible or was always at the midpoint of the target object. When the target
      object was viewed against either a floor or a ceiling plane, some observers used
      DH, but others (erroneously) used HPP. In general, when DH is defined and
      unambiguous, observers use it to determine the relative distance to objects, but
      when DH is undefined and/or ambiguous, at least some observers use HPP.

PMID- 20139459
TI  - 3-D localization of virtual sound sources: effects of visual environment,
      pointing method, and training.
AB  - The ability to localize sound sources in three-dimensional space was tested in
      humans. In Experiment 1, naive subjects listened to noises filtered with subject
      specific head-related transfer functions. The tested conditions included the
      pointing method (head or manual pointing) and the visual environment (VE;
      darkness or virtual VE). The localization performance was not significantly
      different between the pointing methods. The virtual VE significantly improved the
      horizontal precision and reduced the number of front-back confusions. These
      results show the benefit of using a virtual VE in sound localization tasks. In
      Experiment 2, subjects were provided with sound localization training. Over the
      course of training, the performance improved for all subjects, with the largest
      improvements occurring during the first 400 trials. The improvements beyond the
      first 400 trials were smaller. After the training, there was still no significant
      effect of pointing method, showing that the choice of either head- or manual
      pointing method plays a minor role in sound localization performance. The results
      of Experiment 2 reinforce the importance of perceptual training for at least 400
      trials in sound localization studies.

PMID- 20139460
TI  - Auditory color constancy: calibration to reliable spectral properties across
      nonspeech context and targets.
AB  - Brief experience with reliable spectral characteristics of a listening context
      can markedly alter perception of subsequent speech sounds, and parallels have
      been drawn between auditory compensation for listening context and visual color
      constancy. In order to better evaluate such an analogy, the generality of
      acoustic context effects for sounds with spectral-temporal compositions distinct
      from speech was investigated. Listeners identified nonspeech sounds-extensively
      edited samples produced by a French horn and a tenor saxophone-following either
      resynthesized speech or a short passage of music. Preceding contexts were
      "colored" by spectral envelope difference filters, which were created to
      emphasize differences between French horn and saxophone spectra. Listeners were
      more likely to report hearing a saxophone when the stimulus followed a context
      filtered to emphasize spectral characteristics of the French horn, and vice
      versa. Despite clear changes in apparent acoustic source, the auditory system
      calibrated to relatively predictable spectral characteristics of filtered
      context, differentially affecting perception of subsequent target nonspeech
      sounds. This calibration to listening context and relative indifference to
      acoustic sources operates much like visual color constancy, for which reliable
      properties of the spectrum of illumination are factored out of perception of
      color.

PMID- 20139461
TI  - Listeners' perception of compensatory shortening.
AB  - English exhibits compensatory shortening, whereby a stressed syllable followed by
      an unstressed syllable is measured to be shorter than the same stressed syllable
      alone. This anticipatory shortening is much greater than backward shortening,
      whereby an unstressed syllable is measured to shorten a following stressed
      syllable. We speculated that measured shortening reflects not true shortening,
      but coarticulatory hiding. Hence, we asked whether listeners are sensitive to
      parts of stressed syllables hidden by following or preceding unstressed
      syllables. In two experiments (Experiments 1A and 1B), we found the point of
      subjective equality-that is, the durational difference between a stressed
      syllable in isolation and one followed by an unstressed syllable-at which
      listeners cannot tell which is longer. In a third experiment (Experiment 2), we
      found the point of subjective equality for stressed monosyllables and disyllables
      with a weak-strong stress pattern. In all of the experiments, the points of
      subjective equality occurred when stressed syllables in disyllables were measured
      to be shorter than those in monosyllables, as if the listeners heard the
      coarticulatory onset or the continuation of a stressed syllable within unstressed
      syllables.

PMID- 20139462
TI  - Shortening of subjective tone intervals followed by repetitive tone stimuli.
AB  - Accumulated evidence shows that a subjective time interval is lengthened by
      preceding or concurrent presentation of flickers or repetitive tone stimuli that
      have been hypothesized to increase the frequency of pulse generation by a brain
      pacemaker. In the present study, we presented a series of repetitive tone stimuli
      after an interval that started and ended with tone markers. We found that
      subjective perception of the preceding interval was not lengthened but shortened
      by the tone stimuli that followed the interval. The perceived duration decreased
      as the frequency of the repetitive tone stimuli increased. The effect disappeared
      when the repetitive tone stimuli were delivered with a delay of 500 msec after
      the test interval or when continuous sound was delivered instead of delivering a
      rapid series of tones. On the basis of the results, we propose that the pulse
      count accumulated during a test interval was normalized by the clock frequency
      just after the test interval in a postdictive manner.

PMID- 20139463
TI  - Improved segregation of simultaneous talkers differentially affects perceptual
      and cognitive capacity demands for recognizing speech in competing speech.
AB  - Perception of speech in competing speech is facilitated by spatial separation of
      the target and distracting speech, but this benefit may arise at either a
      perceptual or a cognitive level of processing. Load theory predicts different
      effects of perceptual and cognitive (working memory) load on selective attention
      in flanker task contexts, suggesting that this paradigm may be used to
      distinguish levels of interference. Two experiments examined interference from
      competing speech during a word recognition task under different perceptual and
      working memory loads in a dual-task paradigm. Listeners identified words produced
      by a talker of one gender while ignoring a talker of the other gender. Perceptual
      load was manipulated using a nonspeech response cue, with response conditional
      upon either one or two acoustic features (pitch and modulation). Memory load was
      manipulated with a secondary task consisting of one or six visually presented
      digits. In the first experiment, the target and distractor were presented at
      different virtual locations (0 degrees and 90 degrees , respectively), whereas in
      the second, all the stimuli were presented from the same apparent location.
      Results suggest that spatial cues improve resistance to distraction in part by
      reducing working memory demand.

PMID- 20139464
TI  - Haptic perception of volume and surface area of 3-D objects.
AB  - Haptic perception of volume (Experiment 1) and surface area (Experiment 2) was
      studied with tetrahedrons, cubes, and spheres as stimuli (2-14 cm(3)). The
      results of Experiment 1 showed that subjects perceived a tetrahedron to be larger
      in volume than either a cube or a sphere of the same physical volume and that
      they perceived a cube to be larger than a sphere. This pattern was independent of
      object size. The biases were smaller in conditions with mass information than in
      those without. The average biases in the different conditions ranged from 7% to
      67%. Analyses revealed that the subjects apparently based their volume judgments
      on the surface area of objects. Experiment 2 showed that surface area itself
      could be perceived accurately, almost independently of the objects' shape.
      Experiment 3 investigated volume perception of objects in the absence of surface
      area (wire-frame objects) and showed larger biases than those observed with solid
      objects. With wire-frame objects, the maximal distance between two vertex points
      was probably the dimension on which the volume judgment was based. In conclusion,
      haptic volume perception of geometric objects has to be inferred from other
      object properties, but surface area can be perceived unbiased.

PMID- 20139465
TI  - A prospective view of the impact of prime validity on response speed and
      selection in the arrow classification task with free choice trials.
AB  - Bodner and Masson (2001, 2003, 2004) demonstrated that masked priming effects in
      many cognitive tasks become larger when the proportion of related trials
      increases (prime validity effects). Those authors claimed that these effects are
      due to participants' recruiting prime information to aid target processing when
      it is useful to do so (e.g., there are a large number of related trials-the
      memory recruitment account). Bodner and Mulji (in press) recently reported
      similar effects in an arrow classification task with free choice trials. In the
      present research, we examined whether the memory recruitment account can
      adequately explain prime validity effects in that task. In this experiment,
      participants classified arrow direction (i.e., left-right) and responded to free
      choice stimuli (i.e., two-sided arrows that allow either a left or right
      response) following arrow primes when the prime-target relationship for the arrow
      target trials was always congruent, always incongruent, or unpredictive. Prime
      validity effects for the either-way targets emerged with both 77- and 165-msec
      prime-target intervals. The results in the unpredictive conditions, however,
      suggest that those effects were due to the impact of automatic response biases
      initially created by the prime, which participants attempt to suppress when it is
      advantageous to do so.

PMID- 20139466
TI  - On the choice of adequate randomization ranges for limiting the use of unwanted
      cues in same-different, dual-pair, and oddity tasks.
AB  - A major concern when designing a psychophysical experiment is that participants
      may use a stimulus feature (cue) other than that intended by the experimenter.
      One way to avoid this problem is to apply random variations to the corresponding
      feature across stimulus presentations to make the unwanted cue unreliable. An
      important question facing experimenters who use this randomization (roving)
      technique is how large the randomization range should be to ensure that the
      participants cannot achieve a certain proportion correct by using the unwanted
      cue, while at the same time avoiding unnecessary interference of the
      randomization with task performance. Previous researchers have provided formulas
      for the selection of adequate randomization ranges in yes-no and multiple
      alternative forced choice tasks. In this article, we provide figures and tables
      that can be used to select randomization ranges that are better suited to
      experiments involving a same-different, dual-pair, or oddity task.

PMID- 20139467
TI  - A novel method for the construction of verbal rating scales at the ratio scale
      level of measurement precision: the multidimensional-psychophysical scaling
      procedure (M-PSP).
AB  - The multidimensional-psychophysical scaling procedure was employed to construct
      verbal rating scales at the ratio scale level of measurement precision. The
      multidimensional individual differences scaling model (INDSCAL) demonstrated a
      one-dimensional solution in the group stimulus space, with the eight verbal
      descriptors and the eight electrical stimulus intensities interdigitated with
      respect to their perceived strength. A plot of these stimulus coordinates against
      a scale of electrical intensities in milliwatts yielded an exponential function.
      To construct the rating scales, the four attributes that could be discerned
      within the dimension-namely, perceived intensities of the electrical stimuli and
      the attributes of the subjective experiences evoked by the electrical stimuli:
      pain qualities, somatosensory qualities, and emotional qualities-were plotted as
      separate scales against a subjective intensity scale. Although not presented
      here, INDSCAL also yields a subject coordinate space that quantifies the
      importance or saliency to each subject of each pole, stoical or complainer, of
      the dimension.

PMID- 20139468
TI  - Modeling macro-molecular interfaces with Intervor.
AB  - SUMMARY: Intervor is a software computing a parameter-free representation of
      macro-molecular interfaces, based on the alpha-complex of the atoms. Given two
      interacting partners, possibly with water molecules squeezed in-between them,
      Intervor computes an interface model which has the following characteristics: (i)
      it identifies the atoms of the partners which are in direct contact and those
      whose interaction is water mediated, (ii) it defines a geometric complex
      separating the partners, the Voronoi interface, whose geometric and topological
      descriptions are straightforward (surface area, number of patches, curvature),
      (iii) it allows the definition of the depth of atoms at the interface, thus going
      beyond the traditional dissection of an interface into a core and a rim. These
      features can be used to investigate correlations between structural parameters
      and key properties such as the conservation of residues, their polarity, the
      water dynamics at the interface, mutagenesis data, etc. AVAILABILITY: Intervor
      can be run from the web site http://cgal.inria.fr/abs/Intervor or upon
      downloading the binary file. Plugins are also made available for VMD and Pymol.

PMID- 20139470
TI  - Snoopy--a unifying Petri net framework to investigate biomolecular networks.
AB  - SUMMARY: To investigate biomolecular networks, Snoopy provides a unifying Petri
      net framework comprising a family of related Petri net classes. Models can be
      hierarchically structured, allowing for the mastering of larger networks. To move
      easily between the qualitative, stochastic and continuous modelling paradigms,
      models can be converted into each other. We get models sharing structure, but
      specialized by their kinetic information. The analysis and iterative reverse
      engineering of biomolecular networks is supported by the simultaneous use of
      several Petri net classes, while the graphical user interface adapts dynamically
      to the active one. Built-in animation and simulation are complemented by exports
      to various analysis tools. Snoopy facilitates the addition of new Petri net
      classes thanks to its generic design. AVAILABILITY: Our tool with Petri net
      samples is available free of charge for non-commercial use at http://www
      dssz.informatik.tu-cottbus.de/snoopy.html; supported operating systems: Mac OS X,
      Windows and Linux (selected distributions).

PMID- 20139469
TI  - Metscape: a Cytoscape plug-in for visualizing and interpreting metabolomic data
      in the context of human metabolic networks.
AB  - SUMMARY: Metscape is a plug-in for Cytoscape, used to visualize and interpret
      metabolomic data in the context of human metabolic networks. We have developed a
      metabolite database by extracting and integrating information from several public
      sources. By querying this database, Metscape allows users to trace the
      connections between metabolites and genes, visualize compound networks and
      display compound structures as well as information for reactions, enzymes, genes
      and pathways. Applying the pathway filter, users can create subnetworks that
      consist of compounds and reactions from a given pathway. Metscape allows users to
      upload experimental data, and visualize and explore compound networks over time,
      or experimental conditions. Color and size of the nodes are used to visualize
      these dynamic changes. Metscape can display the entire metabolic network or any
      of the pathway-specific networks that exist in the database. AVAILABILITY:
      Metscape can be installed from within Cytoscape 2.6.x under 'Network and
      Attribute I/O' category. For more information, please visit
      http://metscape.ncibi.org/tryplugin.html.

PMID- 20139471
TI  - Biomechanical evaluation of the acromioclavicular capsular ligaments and
      reconstruction with an intramedullary free tissue graft.
AB  - BACKGROUND: Multiple techniques have been reported to treat chronic
      acromioclavicular joint injuries. However, many have failed to restore native
      stability, and few have addressed reconstructing the acromioclavicular ligaments.
      HYPOTHESIS: An intramedullary free semitendinosus graft reconstruction of the
      acromioclavicular ligaments will demonstrate joint stability comparable with that
      of the intact acromioclavicular joint. STUDY DESIGN: Controlled laboratory study.
      METHODS: Six matched pairs of cadaveric specimens with only the acromioclavicular
      capsule/ligament intact were tested at 10 N and 15 N in the anteroposterior and
      superoinferior directions under acromioclavicular joint compression loads of 10
      N, 20 N, and 30 N. One of each pair randomly underwent reconstruction of the
      acromioclavicular ligaments with an intramedullary free semitendinosus graft, and
      the translational testing was repeated. Both the intact and reconstructed
      specimens then underwent load-to-failure testing via superior clavicle
      distraction at a rate of 50 mm/min. RESULTS: The reconstructed specimens
      reproduced the stability of the intact specimens during all translational and
      joint compression load trials. Progressively decreased translation was observed
      for the reconstructed specimens that reached statistical significance (P <.05) in
      the anteroposterior direction at 10 N of joint compression under 10-N and 15-N
      translation loads and in the superoinferior direction at 10 N of joint
      compression and 10-N translational load. With regard to load-to-failure testing,
      the reconstructed specimens demonstrated significantly lower (P < .05) values for
      linear stiffness, yield load, ultimate load, and energy absorbed, ranging from
      40% to 48% of the values for the intact specimens. CONCLUSION: Intramedullary
      free semitendinosus graft reconstruction of the acromioclavicular ligaments
      reproduced anteroposterior and superoinferior translational stability and
      partially reproduced load-to-failure characteristics. CLINICAL RELEVANCE: When
      surgical intervention after higher grade acromioclavicular joint injuries is
      required, reconstruction of the acromioclavicular ligaments with an
      intramedullary free semitendinosus graft, in addition to reconstructing the
      coracoclavicular ligaments, may result in improved stability of the joint
      complex, improved maintenance of joint reduction, and increased patient
      satisfaction.

PMID- 20139472
TI  - Rational use of antibiotics for pneumonia.

PMID- 20139473
TI  - Acute respiratory infection Boston university's collaborative research work in
      the last decade.
AB  - In the last decade, Boston University, in collaboration with the Child and
      Adolescent Health Division of the World Health Organization (WHO), has conducted
      a number of multi-center clinical trials aimed at reducing the childhood
      mortality associated with acute respiratory infections (ARI). These studies have
      addressed questions of program relevance and challenges faced by implementing WHO
      case management guidelines. The spectrum of research studies has extended from
      endorsing WHO guidelines for using antibiotics in all children with fast
      breathing to evaluation of ARI guidelines for management of severe pneumonia.
      Research priorities have included assessing the capacity of community health
      workers to provide appropriate early treatment to children with pneumonia and to
      manage both pneumonia and malaria in countries with a dual burden of these
      childhood illnesses. These contributions are likely to have a long lasting impact
      on reducing the mortality and morbidity associated with childhood pneumonia.

PMID- 20139474
TI  - 2009 pandemic influenza in India.
AB  - Pandemic-09-H1N1 virus caused the pandemic starting in the second quarter of
      2009. The world was prepared to face the pandemic since it was anticipated for
      over one decade. Most countries, including India, had made detailed pandemic
      preparedness plans well ahead of its actual occurrence. The infection rapidly
      spread to the whole country within 2-3 months. The national tactics were to slow
      down its importation through international air travelers and to slow down its
      spread in cities and major towns. More than 75% of all infected persons were
      urban dwellers, suggesting that efforts were concentrated in urban communities.
      In general the illness of pandemic influenza has been similar to endemic/seasonal
      influenza; however, there is insufficient epidemiological and clinical data on
      the latter. We hope that the unprecedented experience of managing the pandemic
      will encourage the Government of India to plan to confront endemic/seasonal
      influenza more systematically. The pandemic seems to have reached a peak in
      September/October and has been on the decline since then.

PMID- 20139475
TI  - Vaccines as tools to reduce ARI burden: merits and some inherent verticality in
      the debate.

PMID- 20139476
TI  - Evidence-based treatment of tuberculosis for children: the unfinished agenda.

PMID- 20139477
TI  - Consensus statement on childhood tuberculosis.
AB  - JUSTIFICATION: Revised National Tuberculosis Control Program (RNTCP) has focused
      on adults with smear positivity a tool not so well used in children with
      tuberculosis. There is a need to redefine standardization of diagnosis and
      management protocols for childhood tuberculosis. PROCESS: Indian Academy of
      Pediatrics constituted a Working Group to develop consensus statement on
      childhood tuberculosis (TB). Members of the Group were given individual
      responsibilities to review the existing literature on different aspects of the
      childhood TB. The group deliberated and developed a consensus which was
      circulated to all the members for review. Efforts were made to ensure that the
      recommendations are standardized. OBJECTIVES: To produce recommendations and
      standard protocols for reasonably accurate diagnosis and rational treatment of
      tuberculosis in children. RECOMMENDATIONS: Fever and or cough > 2 weeks with loss
      of weight and recent contact with infectious case should arouse suspicion of TB.
      Chest Xray and trial with broad-spectrum antibiotic for 7-10 days is justified.
      In case of clinical and radiological non-response, Mantoux test and sputum or
      gastric aspirate for AFB is recommended. If AFB is positive, diagnosis is
      confirmed. If AFB is negative but chest Xray is suggestive and Mantoux test is
      positive, it is a probable case and if these tests are negative, alternate
      diagnosis must be sought and referral made to an expert. Ideally it is
      recommended to use 1TU of PPD for Mantoux test but 2 or 5 TU may be acceptable
      (but less preferred). Cut-off point of 10 mms for natural infection may be used
      for test done with 1, 2 or 5 TU. There is no linear relation of reaction to
      tuberculin strength and so no more than 5 TU should be used. BCG test is not
      recommended. Diagnosis must not be made without an attempt to look for AFB in
      gastric aspirate or sputum, as it is possible to get AFB even in primary complex.
      Elisa and PCR tests for TB are not recommended. There is no place for trial of
      anti tubercular therapy. Lymphnode enlargement > 2 cm with or without typical
      findings suggestive of TB and failure of antibiotic response demands FNAC for
      histopathology and bacteriology. Clinical suspicion of tubercular meningitis
      (TBM) should be confirmed by CSF examination and CT scan though none of these
      investigations are confirmatory and hence should not be considered in isolation.
      CSF tests for TB antibody and PCR are not recommended for routine use. Diagnosis
      of abdominal TB is made on circumstantial evidence and there are no standard
      guidelines. For treatment, disease is divided into three categories. The Category
      I and III are recommended for different types of new cases i.e. those who have
      received treatment for not more than 4 weeks. Category III includes primary
      pulmonary complex, one site peripheral lymphadenitis and pleural effusion, while
      all other forms of TB are included in Category I, that corresponds to smear
      positive TB in adults. This is because AFB is often found in many Category I
      disease in children. Category II includes defaulters, relapses and failure cases
      irrespective of the site of disease. Standard protocol is followed for each of
      these categories. Intermittent thrice weekly therapy with higher dose has been
      found to be equally effective as daily therapy and so is recommended in DOTS
      Direct Observed Therapy Short term. Compliance of treatment must be ensured.
      Repeat chest X-ray is ideal at the end of therapy. Liver function tests are not
      routinely recommended. Recommendations are also made for special situations such
      as MDRTB, TB and HIV and neonate born to mother suffering from TB.

PMID- 20139478
TI  - Pertinent issues in diagnosis and management of wheezing in under-five children
      at community level.
AB  - Wheezing in acute respiratory infections is a rule rather than exception. A large
      proportion of children (up to 75%) having pneumonia or severe pneumonia as per
      WHO definitions have associated wheezing. The current strategies to diagnose and
      manage wheeze in the community need to be updated, as audible wheeze is present
      in only less than one third of wheezy children, and can not be relied upon
      solely. A history of previous episodes of respiratory distress has a high
      sensitivity to diagnose wheezy disorders. In a significant proportion of
      children, the respiratory rate comes back to normal and the chest indrawing
      disappear after two to three cycles of inhaled bronchodilator medications.
      Operational research is needed to evaluate the feasibility of including
      management of wheezing in the community based ARI management programs.

PMID- 20139479
TI  - Zinc supplementation for prevention or treatment of childhood pneumonia: a
      systematic review of randomized controlled trials.

PMID- 20139480
TI  - Current status of tuberculosis and acute respiratory infections in India: much
      more needs to be done!

PMID- 20139481
TI  - Prevalence of Mycobacterium tuberculosis infection in children in western Uttar
      Pradesh.
AB  - This study was conducted to estimate the prevalence of tubercular infection and
      compute the Annual risk of tuberculosis infection (ARTI) in Bijnor district of
      western Uttar Pradesh through a hospital-based tuberculin survey conducted at a
      pediatric hospital. A total of 1085 children below 18 years (0-4 years 866, 5-17
      years 219), attending the out-patient department during October 2007 through
      September 2008 were included. Tuberculin skin test using standard PPD RT23 with
      Tween 80 was performed on every 4th child attending the out-patient department
      and induration was measured after 48 to 72 hours. Using a cut-off of 15 mm among
      0-4 y aged children, the average prevalence rate was 7.4%, and using cut-off of
      10 mm in 5-17 y age group the average prevalence rate was 26.9%. ARTI was 4.11%
      (95% CI 3.09-5.14) and 3.50 % (2.46-4.48), respectively in the two age groups.

PMID- 20139482
TI  - H1N1 guidelines.

PMID- 20139483
TI  - Knowledge, attitude and practices regarding novel H1N1 (swine) flu among
      pediatricians of Chandigarh.

PMID- 20139485
TI  - The synthesis and hydrogen storage properties of pure nanostructured Mg2FeH6.
AB  - In this work, pure nanostructured Mg(2)FeH(6) is successfully synthesized by
      sintering of a mixture of 2Mg + Fe nanoparticles. The successful preparation of
      pure Mg(2)FeH(6) can be attributed to the small particle sizes of Mg and Fe
      nanoparticles prepared by hydrogen plasma-metal reaction (HPMR), which benefits
      the synthesis. The hydrogen storage properties of Mg(2)FeH(6) and the synthesis
      mechanism of the Mg-Fe-H system are studied. The sample desorbs 5.0 wt% of
      hydrogen rapidly in 6 min under an initial hydrogen pressure of approximately 100
      Pa at 623 K. The enthalpy and entropy of the reaction are deduced from the
      equilibrium plateau pressures of the desorption isotherms. The obtained
      Mg(2)FeH(6) shows favorable hydrogen storage properties due to the specific
      nanostructure of the materials.

PMID- 20139486
TI  - DNA-decorated carbon-nanotube-based chemical sensors on complementary metal oxide
      semiconductor circuitry.
AB  - We present integration of single-stranded DNA (ss-DNA)-decorated single-walled
      carbon nanotubes (SWNTs) onto complementary metal oxide semiconductor (CMOS)
      circuitry as nanoscale chemical sensors. SWNTs were assembled onto CMOS circuitry
      via a low voltage dielectrophoretic (DEP) process. Besides, bare SWNTs are
      reported to be sensitive to various chemicals, and functionalization of SWNTs
      with biomolecular complexes further enhances the sensing specificity and
      sensitivity. After decorating ss-DNA on SWNTs, we have found that the sensing
      response of the gas sensor was enhanced (up to approximately 300% and
      approximately 250% for methanol vapor and isopropanol alcohol vapor,
      respectively) compared with bare SWNTs. The SWNTs coupled with ss-DNA and their
      integration on CMOS circuitry demonstrates a step towards realizing ultra
      sensitive electronic nose applications.

PMID- 20139487
TI  - Scanning probe nanoscale patterning of highly ordered pyrolytic graphite.
AB  - In this work we present precision scanning probe etching of highly ordered
      pyrolytic graphite. We corroborate that the lithography is due to an
      electrochemical, polarity-dependent, meniscus-mediated etching of the carbon
      surface. By changing the etching temperature, we are able to reduce the feature
      size by 24%. External feedback control and probe tip cleaning enables desired cut
      patterns with high precision. Using a feedback-controlled atomic force
      microscope, we demonstrate an array of 105 trenches using 370 etching operations,
      with 136 +/- 6 and 183 +/- 5 nm precision over an area of 2.5 microm x 2.5
      microm. This results in a precision of 4.4% and 2.7%, respectively.

PMID- 20139488
TI  - A passive wireless hydrogen surface acoustic wave sensor based on Pt-coated ZnO
      nanorods.
AB  - Using a passive wireless sensor to detect hydrogen can reach the goals of
      reducing cost and increasing the lifetime since the sensor can work without
      batteries. In this paper, a passive wireless hydrogen SAW sensor operating at
      room temperature has been achieved by combining a SAW tag and a resistive
      hydrogen sensor. The SAW tag is fabricated on a 128 degrees YX-LiNbO(3) substrate
      and its central frequency is 433 MHz. The resistive hydrogen sensor with the Pt
      coated ZnO nanorods as the sensing film has the advantages of high stability,
      good repeatability and simple fabrication. The ZnO nanorods are synthesized by
      using the aqueous solution method and the Pt coating is employed as a catalyst
      for the hydrogen detection. The property of the resistive hydrogen sensor is
      examined before combining with the SAW tag. Results show that the resistance
      changes caused by the variations of relative humidity and temperature are
      negligible. Finally, the hydrogen SAW sensor is configured and measured
      wirelessly for various hydrogen concentrations at room temperature. The
      difference of the relative return loss caused by the hydrogen concentration
      variation is obvious and recognizable. All responses show that the proposed
      hydrogen sensor not only has good repeatability and high sensitivity but is
      capable of passive wireless detection.

PMID- 20139489
TI  - Parallel-aligned GaAs nanowires with 110 orientation laterally grown on [311]B
      substrates via the gold-catalyzed vapor-liquid-solid mode.
AB  - We report parallel aligned GaAs nanowires (NWs) with 110 orientation laterally
      grown on [311]B substrates via the vapor-liquid-solid mode and demonstrate their
      controllability and growth mechanism. We control the size, density, and site of
      the lateral NWs by using size- and density-selective Au colloidal particles and
      Au dot arrays defined by electron-beam lithography. The lateral NWs grow only
      along the [110] and [Formula: see text] directions and formation of the stable
      facets of (111)B and (001) on the sides of the lateral NWs is crucial for lateral
      NW growth. We clarify the growth mechanism by comparing the growth results on
      [311]B, (311)A, and (001) substrates and the surface energy change of lateral and
      freestanding NWs.

PMID- 20139490
TI  - Nanobubble-assisted formation of carbon nanostructures on basal plane highly
      ordered pyrolytic graphite exposed to aqueous media.
AB  - Ambient gas nanobubbles of size approximately 10(1)-10(2) nm occupying the
      hydrophobic surface of basal plane highly ordered pyrolytic graphite (HOPG)
      immersed in aqueous media at room temperature cause exfoliation of the top
      graphene layers, as revealed by both in situ and ex situ atomic force microscope
      (AFM) imaging. The formation of nanoparticles composed mostly from graphene-based
      nanoscrolls, nanohorn-like and onion-like nanostructures was resolved by high
      resolution transmission electron microscopy (TEM) and examined by diffraction and
      x-ray photoelectron spectroscopy (XPS) analyses. The diameter of nanostructures
      varied from about 5 nm for single-layered scrolls to tens of nanometres for
      multishells. Raman spectroscopy confirmed the structural rearrangement of the
      HOPG basal plane after the above-mentioned treatment. The implications for
      nanobubble interfacial forces are discussed.

PMID- 20139491
TI  - Mn-doped ZnO nanonails and their magnetic properties.
AB  - Mn-doped ZnO nanonails composed of hexagonal caps and shafts with large doping
      concentrations from 11.7 to 35.1 at.% were synthesized via a simple and
      straightforward non-aqueous solution-based route. The chemical composition,
      morphology and structure of the obtained nanocrystals were characterized by
      energy-dispersive x-ray analysis, powder x-ray diffraction and transmission
      electron microscopy. The results show that the nanonails possess a single-crystal
      wurtzite structure. Electron paramagnetic resonance results indicate that Mn(2+)
      ions substitute for the zinc sites in the ZnO matrix, which is also confirmed by
      high-resolution electron microscopy. Thermal tolerance experiments show that the
      Mn-doped nanonails can maintain their crystalline structure up to 700 degrees C.
      The influence of reaction conditions on the size and shape of the ZnO-based
      samples has been investigated in detail, and the possible growth mechanism of the
      nanonails has also been discussed.

PMID- 20139492
TI  - Enhanced microwave absorption of Fe nanoflakes after coating with SiO2 nanoshell.
AB  - Fe nanoflakes were prepared by the ball-milling technique, and then were coated
      with 20 nm-thick SiO(2) to prepare Fe/SiO(2) core-shell nanoflakes. Compared with
      the uncoated Fe nanoflakes, the permittivity of Fe/SiO(2) nanoflakes decreases
      dramatically, while the permeability decreases slightly. Consequently, reflection
      losses exceeding - 20 dB of Fe/SiO(2) nanoflakes are obtained in the frequency
      range of 3.8-7.3 GHz for absorber thicknesses of 2.2-3.6 mm, while the reflection
      loss of uncoated Fe nanoflakes almost cannot reach - 10 dB in the same thickness
      range. The enhanced microwave absorption of Fe/SiO(2) nanoflakes can be
      attributed to the combination of the proper electromagnetic impedance match due
      to the decrease of permittivity and large magnetic loss due to strong and
      broadband natural resonance. The key to the combination is the coexistence of the
      nanoshell microstructure and the nanoflake morphology.

PMID- 20139493
TI  - Synthesis of Ag/CNT hybrid nanoparticles and fabrication of their nylon-6 polymer
      nanocomposite fibers for antimicrobial applications.
AB  - Ag-coated CNTs hybrid nanoparticles (Ag/CNTs) were prepared by ultrasonic
      irradiation of dimethylformamide (DMF) and silver (I) acetate precursors in the
      presence of CNTs. The morphology of Ag/CNTs was characterized using x-ray
      diffraction and transmission electron microscopy (TEM) techniques. The Nylon-6
      powder and 1 wt% Ag/CNTs mixture was dispersed uniformly using a noncontact
      spinning technique. The dried mixture was melted in a single screw extrusion
      machine and then extruded through an orifice. Extruded filaments were later
      stretched and stabilized by sequentially passing them through a set of tension
      adjusters and a secondary heater. The Nylon-6/Ag/CNT hybrid polymer nanocomposite
      (HPNC) fibers, which were of approximately 80 microm size, were tested for their
      tensile properties. The failure stress and modulus of the extruded HPNC fibers
      (doped with 1% Ag/CNTs) was about 72.19 % and 342.62% higher than the neat
      extruded Nylon-6 fiber, respectively. DSC results indicated an increase in the
      thermal stability and crystallization for HPNC fibers. The antibacterial activity
      of the Ag-coated CNTs, commercial Ag, neat Nylon-6 and plain CNTs were evaluated.
      Ag-coated CNTs at 25 microg demonstrated good antimicrobial activity against four
      common bacterial pathogens as tested by the Kirby-Bauer assay. The mean diameters
      of the zones of inhibition were 27.9 +/- 6.72 mm, 19.4 +/- 3.64 mm, 21.9 +/- 4.33
      mm, and 24.1 +/- 4.14 mm, respectively, for Staphylococcus aureus, Streptococcus
      pyogenes, Escherichia coli and Salmonella enterica serovar Typhimurium. By
      comparison, those obtained using the broad spectrum antibiotic amoxicillin
      clavulanic acid were 37.7 +/- 2.13 mm, 28.6 +/- 4.27 mm, 22.6 +/- 1.27 mm, and
      27.0 +/- 1.41 mm, respectively, for the same strains. The zones of inhibition
      obtained for Nylon-6 Ag-coated CNT powder at 25 microg were also high, ranging
      from 15.2 to 25.3 mm in contrast to commercial silver or neat Nylon-6, which did
      not inhibit the bacterial strains tested. Further, the Nylon-6 nanocomposite
      fibers infused with Ag/CNTs inhibited bacterial growth by 11-20%. Our results
      suggest that nylon nanocomposite fibers infused with Ag-coated CNTs have
      significant antimicrobial activity.

PMID- 20139494
TI  - Erythropoietin in traumatic brain injury: the "golden bullet" on the horizon?

PMID- 20139495
TI  - Time to improve awareness of restless legs syndrome.

PMID- 20139496
TI  - Toxic neuropathies.
AB  - Toxic neuropathies generally result in length dependent axonal neuropathy with
      the exception of diphtheria and a few toxic neuropathies. In spite of occurrence
      of diphtheria in India there is paucity of published reports on diphtheritic
      neuropathy. Arsenic neuropathy commonly occurs in Bengal and Bangladesh because
      of ground water contamination whereas in Punjab it is due to contamination of
      opium. Lead neuropathy is rare and has been reported in battery workers and
      silver refining workers. It produces motor neuropathy resulting in foot drop and
      wrist drop. Organophosphates are used as pesticides, industrial chemicals and
      food adulterant. Certain organophosphates such as triorthocresyl phosphate used
      for or oil adulteration inhibit neurotoxic esterase and result in a delayed type
      of axonal neuropathy. Alcohol related neuropathy is a controversial issue whether
      it is due to alcohol related toxicity or due to nutritional deficiencies. Indian
      studies have revealed that neuropathy occurs both in alcoholic and nonalcoholic
      cirrhosis. Hexane neuropathy is reported in screen printers and these cases
      highlight the need for better preventive and occupational measures. Iatrogenic
      toxic neuropathies have been reported with cisplatin and vincristine. Because of
      geographical, occupational and health related conditions toxic neuropathies are
      likely to be more common than reported and greater awareness is needed.

PMID- 20139497
TI  - Transplantation and stem cell research in neurosciences: where does India stand?
AB  - The nearly absent ability of the neurons to regenerate or multiply has prompted
      neuroscientists to search for the mean to replace damaged or dead cells. The
      failed attempts using adult tissue, initiated nearly a century ago, ultimately
      brought rays of hope when developing fetal neurons were used for transplantation
      in 1970s. The initial excitement was tempered by limited success and ethical
      issues. But these efforts unequivocally established the feasibility of successful
      neural transplantation provided appropriate tissue was available. The ability to
      derive embryonic stem cells with their totipotent potential by Thomson in 1998
      rekindled the interest in their use for replacement therapy for damaged brain
      tissue. The present review surveys the current status of this promising field of
      stem cell research especially in respect to their therapeutic potentials for
      purposes of neural transplantation. A brief account is provided of the ongoing
      Indian efforts in this direction.

PMID- 20139498
TI  - "Free-hand" technique for thoracolumbar pedicle screw instrumentation: critical
      appraisal of current "state-of-art".
AB  - Pedicle screws are widely used for instrumentation of the thoracolumbar spine.
      The anatomic studies performed in the last two decades, detailing the complex
      morphometry and three-dimensional anatomy of the thoracolumbar pedicles, have
      enabled the emergence of the so-called "free-hand" technique of pedicle screw
      placement based exclusively on anatomical parameters. However, in the thoracic
      spine, the benefits of pedicle screws have been tempered by its potential risks,
      such as, spinal canal violation, pedicle fracture, nerve root compression, and
      vascular lesions. Furthermore, the narrow and inconsistent shape of the thoracic
      pedicles, especially in spinal deformity, makes their placement technically
      challenging. In this article, the authors make a critical appraisal of current
      "state-of-art" of "free-hand" technique of pedicle instrumentation, analyzing its
      anatomical basis, surgical technique, present indications and limitations as well
      as the role of adjuvant image-guided and neurophysiological monitoring methods.

PMID- 20139499
TI  - Erythropoietin can promote survival of cerebral cells by downregulating Bax gene
      after traumatic brain injury in rats.
AB  - BACKGROUND: Traumatic brain injury (TBI) is an important cause of adult mortality
      and morbidity. Erythropoietin (Epo) has been shown to promote the viability of
      cerebral cells by upregulating Bcl-2 gene; however, Epo may exert its
      antiapoptotic effect via the differential regulation of the expression of genes
      involved in the apoptotic process. AIM: The present study examined the
      neuroprotective effect of Epo as a survival factor through the regulation of the
      Bax. MATERIALS AND METHODS: Wistar rats were randomly divided into three groups:
      Recombinant human EPO treated (rhEPO) TBI, vehicle-treated TBI, and sham
      operated. Traumatic brain injury was induced by the Feeney free-falling model.
      Rats were killed 5, 12, 24, 72, 120, or 168 h after TBI. Regulation of Bcl-2 was
      detected by reverse transcription-polymerase chain reaction (RT-PCR), western
      blotting and immunofluorescence. RESULTS: Bax mRNA and protein levels were lower
      in the rhEPO)-treated rat brains than in the vehicle-treated rat brains.
      Induction of Bax expression peaked at 24 h and remained stable for 72-120 h in
      vehicle-treated rat brains, whereas induction of Bax expression was only slightly
      elevated in rhEPO-treated rat brains. The number of TdT-mediated dUTP Nick-End
      Labeling(TUNEL)-positive cells in the rhEPO-treated rat brains was far fewer than
      in the vehicle-treated rat brains. CONCLUSIONS: Epo exerts neuroprotective effect
      against traumatic brain injury via reducing Bax gene expression involved in
      inhibiting TBI-induced neuronal cell death.

PMID- 20139500
TI  - The prevalence and clinical features of restless legs syndrome: a door to door
      population study in Orhangazi, Bursa in Turkey.
AB  - BACKGROUND: Restless leg syndrome (RLS) has negative effects on the quality of
      life of the patients. Epidemiological studies on RLS are limited. AIM: To
      determine the prevalence of RLS among people aged 40 years and above in Orhangazi
      district of Bursa, Turkey. MATERIALS AND METHODS: The study was carried out
      between 2004 and 2005. This population-based study was conducted in two phases.
      In the phase 1, residents conducted door-to-door interviews using a short
      questionnaire to determine the possible cases of RLS. In the phase 2, physicians
      ascertained the suspected cases of RLS. Diagnosis of RLS was made using the
      criteria proposed by the International Restless Legs Syndrome Study Group
      (IRLSSG) and also the rating scale for RLS. RESULTS: Out of 1, 256 subjects
      screened in phase 1, 1,124 (89.6%) were included in the study. Also, 161 cases
      with suspected symptoms of RLS were detected in phase 1, 49 of the suspected
      cases could not be evaluated in phase 2. A diagnosis of RLS was also made in 60
      cases during phase 2. CONCLUSIONS: We defined the prevalence of RLS as 9.71%
      among 40 years of age and older population. The prevalence of RLS did not differ
      by age and was 2.6 times more in women. None of the patients were diagnosed as
      RLS sought medical care for the symptoms, possibly due to lack of knowledge of
      patients and physicians about RLS. Prevalence studies help to provide knowledge
      on morbidity, which is essential for diagnosis and early treatment.

PMID- 20139501
TI  - Duchenne muscular dystrophy: a clinical, histopathological and genetic study at a
      neurology tertiary care center in Southern India.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common muscular
      dystrophy that affects young boys and the dystrophin gene on the X chromosome has
      been found to be associated with the disorder. MATERIALS AND METHODS: In this
      prospective study, 112 clinically diagnosed DMD patients had muscle biopsy and
      were tested for exon deletions. Genotyping was also carried out at STR44, STR45,
      STR49 and STR 50 markers in 15 families. RESULTS: Of the 112 clinically suspected
      DMD patients, the diagnosis of DMD was confirmed by histopathology and/or
      genetics in 101 patients. The mean age of onset was 3.1+/-1.44 years (1-6 years)
      and the mean age at presentation was 8.0+/-3.1 years (1.1-18.0 years). Delayed
      motor milestones were present in 63 (62.3%) patients. The mean creatine kinase
      value was 11822.64+/-8206.90 U/L (1240-57,700). Eighty-four patients had muscle
      biopsy and immunohistochemistry was done in 60 muscle samples, all of which
      demonstrated absence of dystrophin staining. Of the 60 dystrophin-negative cases,
      73% showed deletion of at least one exon. Single exon deletion was found in
      20.4%. Distal hotspot Exons 45, 47, 49 and 50 were the commonly deleted xenons
      and the deletion rates were 36%, 35%, 33.7% and 38.5% respectively. CONCLUSIONS:
      In this study population in south India the deletion rate was 73% and were more
      frequent in the distal end exon. With the availability of genetic analysis, the
      first investigation of choice in DMD should be genetic studies and muscle biopsy
      should be considered only if the genetic tests are negative or not available.

PMID- 20139502
TI  - Does intravenous rtPA benefit patients in the absence of CT angiographically
      visible intracranial occlusion?
AB  - BACKGROUND: In patients with acute stroke receiving intravenous tissue
      plasminogen activator (tPA), we postulated that the presence of intracranial
      occlusion on CT angiography (CTA) modifies the benefit of thrombolysis. MATERIALS
      AND METHODS: Using a retrospective cohort design, we identified patients with
      acute ischemic stroke in our CTA database between May 2002 and August 2007. All
      the patients had a CTA within 12 h of onset, a premorbid modified Rankin scale
      (mRS) < or = 1, and a baseline National Institute of Health Stroke Scale
      score(NIHSS)f > or = 6. The primary outcome was early effectiveness of tPA
      defined as an NIHSS score of < or = 2 at 24 h or a 4-point NIHSS improvement at
      24 h. Secondary outcome included mRS < or = 1 at 90 days. The relationship
      between intracranial occlusion on CTA and benefit of tPA was assessed using a
      test for interaction. RESULTS: A total of 287 patients met the criteria
      [occlusion present N =168; (98 with tPA; 70 without tPA) and occlusion absent N =
      119; (52 with tPA; 67 without tPA)]. Those with intracranial occlusion were
      likely to have more severe strokes (NIHSS > or = 15; P < 0.001) and abnormal
      brain imaging (ASPECTS < or =7; P < 0.001). For outcome of 4-point NIHSS score
      improvement at 24 h, benefit from tPA was observed only among patients with a
      visible occlusion (absolute difference in favor of tPA: 20.4% vs. 0.7%; P =
      0.06). CONCLUSION: In patients with acute ischemic stroke, thrombolysis produced
      a better early clinical response among patients with intracranial occlusion,
      which needs to be confirmed in stroke thrombolysis trials.

PMID- 20139503
TI  - Characterization of morphologically benign biologically aggressive meningiomas.
AB  - BACKGROUND: Meningiomas are presently categorized into three grades by World
      Health Organization (WHO). Grade I, in general, is expected to behave in a benign
      fashion. However, a borderline group of grade I meningioma also exists, which may
      behave aggressively. AIMS AND OBJECTIVE: To evaluate the proliferation index and
      p53 antigen expression of meningiomas and correlate with histological grade and
      clinical course. MATERIALS AND METHODS: All 123 cases of meningiomas, diagnosed
      between January 2000 and August 2007, were regraded according to WHO 2000
      criteria. Immunostaining for Ki-67 antigen and p53 protein were performed on 68
      cases selected for the study. RESULTS: Six of the 68 cases presented with
      recurrence. Mean Ki-67 labeling index (Ki-67 LI) was 3.8%, 13.7%, 19.4% for grade
      I, II, and III cases, respectively. Multivariate analysis of mean Ki-67 LI showed
      statistically significant difference between subgroups. Mean p53 expression was
      found to be 15.5%, 57%, 60.8%, and 62.5% for grade I, II, III, and recurrent
      cases, respectively. Multivariate analysis of mean p53 expression showed no
      statistically significant difference between higher grades. All recurrent cases
      were histologically WHO grade I, and showed a high Ki-67 LI and p53 expression
      with mean Ki-67 LI and p53 expression of 8.6% and 62.5% respectively. CONCLUSION:
      Utilization of markers for proliferation and cell cycle regulators in combination
      with histopathological features helps in the identification of a subset of
      biologically aggressive morphologically benign meningiomas.

PMID- 20139504
TI  - Surgical interventions in intracranial arteriovenous malformations: indications
      and outcome analysis in a changing scenario.
AB  - BACKGROUND: Intracranial arteriovenous malformations (AVM) are being increasingly
      managed by multimodality approach. This changing scenario encouraged us to study
      the present state of surgery in intracranial AVMs and the outcomes. MATERIALS AND
      METHODS: Of a total of 868 patients evaluated for suspected or known AVMs between
      January 2000 and July 2008, 790 had intracranial AVMs. The clinical
      characteristics and surgical outcomes of the 111 operated patients were analyzed.
      RESULTS: Of the 111 patients, 73 were males. Clinical features included: Headache
      (70%), loss of consciousness (48%) and seizures (32%). The commonest AVM grade
      was Spetzler-Martin (SM) grade II (41%), 7% had AVM > 6 cm and 78% had evidence
      of bleed. In total 143 surgeries were performed and 22% of patients required
      multiple interventions. The types of surgical interventions included elective
      excision of AVM in 23%, emergency surgery (either AVM excision or evacuation of
      hematoma) in 55%, surgery following radiosurgery/embolization in 5% and
      palliative non-definitive surgeries (e.g. shunt) in 15%. Post-operative
      angiography was done in 67% of patients. Obliteration rates for elective excision
      of AVM in Spetzler Martin Grade I, II, IIIa, IIIb and IV were 100%, 71%, 33%, 50%
      and 67% respectively (mean follow-up:31.6 months). Of 39 patients with residual
      AVMs, 33 received gamma knife and four underwent embolization. Outcome was
      modified Rankin scale (mRS) grade 1 in 34% of patients and the overall favorable
      outcome was 83% and there were six deaths. CONCLUSION: In our patients' cohort
      one in every eight patients required surgery. In intracranial AVMs, surgery still
      plays an important role. In developing countries like India it may be beneficial
      to electively excise Grade I and II AVMs if cost is a consideration.

PMID- 20139505
TI  - Primary central nervous system lymphoma: a profile of 26 cases from Western
      India.
AB  - BACKGROUND: Primary central nervous system (CNS) lymphoma (PCNSL) is a rare
      malignant non-Hodgkin's lymphoma and it accounts for 1% of all intracranial
      tumors. Only a few PCNSL studies have been reported from India, and studies on
      prognostic factors determining outcome, or evaluation of the response to
      currently accepted treatment, are lacking. AIMS: This study attempts to further
      delineate the clinical, radiological and pathological profile of PCNSL in India,
      to evaluate response to treatment and to assess usefulness of the International
      Extranodal Lymphoma Study Group (IELSG) score. SETTINGS AND DESIGN: All patients
      with pathologically proven PCNSL admitted over three years at a large tertiary
      care institution were studied. MATERIALS AND METHODS: Clinical features, IELSG
      prognostic score, imaging and pathological features, and response to treatment
      were evaluated. Results were analyzed using chi 2 test. RESULTS: Of 26 patients
      found, all except two were immunocompetent. Median age at diagnosis was 59 years.
      Focal deficits (76.9%) and neuropsychiatric symptoms (57.6%) were the commonest
      presenting complaints. Except for one case, at least some contrast enhancement
      was seen in brain lesions of all patients. Pathological studies showed high grade
      diffuse large B-cell (DLBCL) histology in 96.2% of patients. Of 22 patients who
      received methotrexate (MTX) based chemotherapy with/without radiotherapy; six
      died, with a response rate of 72.7%. Median survival was 10 months. Median follow
      up duration was 14.5 months. Four patients developed treatment-related cognitive
      decline. All six patients with IELSG score of 4/5 died, while all 16 patients
      with a score of 0-3 survived. CONCLUSIONS: PCNSL presents most commonly in the
      sixth decade with focal neurological deficit, behavioral symptoms and cognitive
      decline. High grade DLBCL is the commonest histological subtype. Steroids should
      ideally be withheld until biopsy as they may confound the diagnosis. Most
      immunocompetent patients respond well to high dose MTX-based chemotherapy
      with/without radiation. High IELSG scores correlate with worse prognosis in
      patients with PCNSL.

PMID- 20139506
TI  - Intra-arterial thrombolysis in acute ischemic stroke: a single center experience.
AB  - Intra-arterial thrombolysis (IAT) is a treatment modality in patients with acute
      large vessel occlusive ischemic stroke. To our knowledge, this is probably the
      first reported study of intra-arterial thrombolysis in acute ischemic stroke from
      India. Of the 17 patients treated who recieved IAT, successful recanalization was
      achieved in nine patients, Thrombolysis in Myocardial Infarction (TIMI) score of
      2 or 3. At 90-day follow-up, eight patients achieved modified Rankin Scale (mRS)
      score of < 2.

PMID- 20139507
TI  - Effects of motor skill practice on reaction time and learning retention in
      Parkinson's disease.
AB  - One of the prominent disturbances in Parkinson's disease (PD) is bradykinesia. We
      studied performance of hand-to-mouth reach reaction time (RT) in right-handed PD
      patients and nine age and sex matched healthy control subjects. Participants
      practiced hand-to-mouth reach skill in response to a visual stimulus, 120 times a
      day for a period of one week. Using Kinemetrix 3D Motion Analysis system, the
      effects of motor skill practice and learning retention were investigated. Pretest
      performance was compared with performances on the second and seventh day of the
      study, and also performance on fourteenth day with no further practice for one
      week. There was a significant reduction in the mean RT in the control group after
      one week of practice. In PD patients the reduction in the mean RT was significant
      between pretest and first test sessions (P < 0.01). However, the difference was
      not significant between the first and second session (P = 0.06) and also between
      the second and third test sessions (P = 1.0). Short-term practice can improve
      bradykinesia in patients with PD but it is not long-lasting.

PMID- 20139508
TI  - Association of meningioma and intracranial aneurysm: report of five cases and
      review of literature.
AB  - Meningiomas associated with intracranial aneurysms are very rare. The co
      existence of both lesions is not only a diagnostic challenge but also has
      important therapeutic implications. We analyzed our experience of five such
      patients, the second largest group in the literature. All the lesions were
      successfully managed surgically. All the patients were female. The location of
      the meningioma was clinoidal (2), planum sphenoidale (1), petroclival (1) and
      pterional (1). Three patients had posterior communicating (PCOM) artery aneurysm
      associated with meningioma. The other aneurysms were internal carotid artery
      (ICA) and anterior communicating artery (ACOM). One patient with pterional
      meningioma had an anomalous meningeal artery arising from the right ophthalmic
      artery. In three patients both lesions underwent treatment at the same sitting.
      In two patients meningioma underwent excision first followed by aneurysm
      clipping. From our experience the incidence of meningiomas associated with
      aneurysms was 1.1%, which is not higher than the incidence of aneurysms in the
      general population.

PMID- 20139509
TI  - A new method of patient's head positioning in suboccipital retrosigmoid approach.
AB  - BACKGROUND: The retrosigmoid approach is a common route to the cerebellopontine
      angle and lateral clivus. Patient's head positioning just before the operation is
      crucial to perform the procedure effectively and safely. AIM: The aim of the
      study is to determine the positional angle of the head on preoperative axial
      sequences of the cranial magnetic resonance imaging (MRI). MATERIALS AND METHODS:
      The angle between the line drawn along the petrous bone ventral to the internal
      auditory canal and the line drawn parallel to the dorsal face of the clivus on
      the axial view of MRI sequences was measured. RESULTS: This method of patient
      positioning has resulted in minimal cerebellar retraction, less time in the
      preoperative preparation period and less postoperative headache and neck pain.
      CONCLUSIONS: This method can provide quick and better exposure of the
      cerebellopontine angle. Preoperative measurement of positional angle on axial MRI
      sequences is a very simple and sufficient way to determine the angle of the head
      that is turned to the contralateral side.

PMID- 20139510
TI  - Treatment of stroke after carotid endarterectomy using intravenous abciximab.
AB  - A 59-year old man developed perioperative stroke following left carotid
      endarterectomy seconday to thrombosis at the endarterectomy site. Transcranial
      Doppler ultrasonography revealed very frequent microembolization in the left
      middle cerebral artery territory. The patient was successfully treated with
      intravenous abciximab with complete neurological recovery.

PMID- 20139511
TI  - Familial recurrent Bell's palsy.
AB  - Bell's palsy is a peripheral facial palsy of sudden onset. The etiology of Bell's
      palsy is unknown and hereditary components may play a role in familial recurrent
      Bell's palsy. We report three families in which eight patients had a total of 12
      episodes of typical Bell's palsy. The pathophysiology of familial recurrent
      Bell's palsy is discussed.

PMID- 20139512
TI  - Coexistence of a single cerebral arteriovenous malformation and spinal
      arteriovenous malformation.
AB  - The coexistence of a cerebral and a spinal arteriovenous malformation (AVM)
      together is extremely rare. We present a 31-year-old woman, who suffered from
      severe root pains in the left upper extremity. Magnetic resonance imaging (MRI)
      revealed the abnormal vessels in the left occipital lobe and upper cervical
      segment of spinal cord. Cerebral angiography and spinal angiogram revealed two
      AVMs: One was in the right occipital lobe and the other was located in the C1-C2
      segments of cervical cord. She had no other vascular lesions, and nor did her
      other family members. As the primary problem in her was left upper extremity root
      pains, which we considered was related to the spinal AVM, the first therapeutic
      treatment was focused on spinal AVM. The cerebral AVM of the right occipital lobe
      was surgically resected after part embolization.

PMID- 20139513
TI  - Movement disorder: a manifestation of HIV and its response to therapy.
AB  - Both akinetic and hyperkinetic movement disorders may rarely be the presenting
      feature of human immunodeficiency virus (HIV) infection. The possible pathogenic
      basis is the involvement of subcortical structures by the HIV infection-related
      pathology. Opportunistic infections, or mass lesions complicating HIV infection.
      In addition dopaminergic dysfunction and medications may also play a role. We
      report a HIV infected male who presented with progressive choreoathetoid
      movements and dystonia. He had remarkable improvement of the movement disorder
      with tetrabenazine and anti-retroviral therapy (HAART) treatment.

PMID- 20139514
TI  - Endoscopic diagnosis of a pineal papillary glioneuronal tumor with extensive
      ventricular involvement: case report with review of literature.
AB  - Papillary glioneuronal tumor (PGNT) is a newly described mixed glioneuronal
      tumor, recently included in the World Health Organization classification of
      central nervous system tumors. We report morphologic and immunohistochemical
      characteristics PGNT of the pineal region extending into the third and lateral
      ventricles in a four-year-old male child and reviewed all the cases reported in
      the international literature till date. In this child the diagnosis of PGNT was
      established by endoscopic biopsy and squash smear examination.

PMID- 20139515
TI  - Desmoplastic non-infantile ganglioglioma: a low-grade tumor, report of two
      patients.
AB  - Desmoplastic infantile gangliogliomas (DIGG) are low-grade (WHO Grade I) tumors
      of early childhood rarely occurring in older children and young adults. The
      mainstay of treatment is surgical. We report two older children with DIGG, both
      showing atypical radiology. One case was treated with radiation. The recurrence
      treated with only surgical excision showed excellent response to treatment.

PMID- 20139516
TI  - Giant intraparenchymal neurocysticercosis: report of surgical aspects two cases.
AB  - Giant parenchymal cysticercosis is a relatively rare condition and surgical
      treatment may be required when it is associated with elevated intracranial
      pressure. We report two patients with giant parenchymal cysticercosis who were
      treated surgically for the elevated intracranial pressure. In both the patients
      the preoperative diagnosis was of a cystic glioma. Total excision of the lesions
      was achieved in both the patients. In countries endemic to neurocysticercosis
      gaint parenchymal cysticercosis should be considered in the differential
      diagnosis of cystic enhancing mass lesion. Surgical excision may be indicated
      when it is associated with elevated intracranial pressure.

PMID- 20139517
TI  - Partial median corpectomy for C2-C3 intradural arachnoid cyst: case report and
      review of the literature.
AB  - Anterior cervical location of arachnoid cyst is a rare and only 22 cases have
      been reported in the literature. The surgical approach was quite varied and
      mostly these cysts were accessed via dorsal laminectomy, with few patients
      developing postoperative neurological deficit. We report a 51-year-old male with
      a cervical arachnoid cyst extending from the dens to the inferior border of the
      C3 body, which was successfully decompressed via an anterior cervical approach
      through the partial corpectomy of C2. This is probably the first case report
      demonstrating the safety of anterior partial median corpectomy of the C2 body
      with micro discectomy of C2-C3 space for excision of the anterior cervical
      archnoid cyst. The additional advantage of this procedure is that it may not
      result in spinal instability.

PMID- 20139518
TI  - Isolated interrupted aortic arch complicated by subarachnoid hemorrhage in an
      adult patient.

PMID- 20139520
TI  - Administration of recombinant tissue plasminogen activator to a case of cerebral
      infarction in the setting of painless aortic dissection.

PMID- 20139519
TI  - First do no harm - a case of limb shaking TIA.

PMID- 20139521
TI  - Familial monomelic amyotrophy (Hirayama disease): two brothers with classical
      flexion induced dynamic changes of the cervical dural sac.

PMID- 20139522
TI  - Acquired hepatolenticular degeneration: is the T1 hyperintensity due to manganese
      deposition?

PMID- 20139523
TI  - Incontinentia pigmenti with sensorimotor polyneuropathy: a novel association.

PMID- 20139524
TI  - Intracerebral hemorrhages in Vogt-Koyanagi-Harada disease.

PMID- 20139525
TI  - Intravascular lymphomatosis with recurrent cerebral hemorrhages.

PMID- 20139526
TI  - Cerebral pial arteriovenous fistula with associated varix treated by direct
      surgery.

PMID- 20139527
TI  - Spinal teratoma with salivary glandular differentiation.

PMID- 20139528
TI  - Intraspinal meningioma in a four-month-old infant.

PMID- 20139529
TI  - Giant solitary fibrous tumor of the middle cranial fossa.

PMID- 20139530
TI  - Lipoma of conus medullaris without spinal dysraphism in an adult.

PMID- 20139531
TI  - Ruptured anterior communicating artery aneurysm presenting with monocular
      blindness.

PMID- 20139532
TI  - Intramedullary Ewing's sarcoma of the spinal cord associated with hydrocephalus.

PMID- 20139533
TI  - Simple depressed skull fracture causing posterior third superior sagittal sinus
      occlusion and elevated intracranial pressure.

PMID- 20139534
TI  - An unusual variant of the ruptured anterior communicating artery aneurysm located
      on the planum sphenoidale.

PMID- 20139535
TI  - Paraganglioma of the cauda equina.

PMID- 20139536
TI  - Methanol poisoning.

PMID- 20139537
TI  - Neurosyphilis.

PMID- 20139538
TI  - Imaging for diagnosis of Marchiafava-Bignami disease.

PMID- 20139539
TI  - Mitroxantrone in multiple sclerosis.

PMID- 20139540
TI  - Oral mucosa grafts for urethral reconstruction.
AB  - BACKGROUND: Urethral reconstruction has continued to present formidable and
      enormous challenges for urologic, paediatric and plastic surgeons as diverse
      opinions have been expressed on the quality and type of ideal substitution
      material. This literature review is aimed at drawing attention of surgeons to the
      versatile nature of oral mucosal grafts. METHODS: A review of the utilization of
      oral mucosa in urethral reconstruction was made. Structured Medline search was
      performed looking at all aspects of utilization of oral mucosa including mucosal
      harvest, donor site morbidity and outcome. RESULTS: The unique demands of the
      urethra set a high standard for autogenous graft substitutes; hence literature
      reports reveal that split and full thickness skin grafts from the scrotum, penis,
      extragenital sites (ureter, saphenous vein, appendix, colon, medial upper arm,
      neck, lateral chest, abdomen, bladder mucosa) and more recently oral mucosa have
      been used. Unlike other tissues, oral mucosa grafts are flexible, easy to harvest
      and trim and have an excellent microvasculature favorable for graft-taking.
      Furthermore, the natural moist location of the oral mucosa in the oral
      environment favours its easy adaptability in the urethral passage thus giving
      good long-term results. However, there are reports of complications at the donor
      site with the commonest being anaesthesia or paraesthesia of the cheek or lips.
      Regional variations of the oral mucosa, length of the graft required, the
      decision to close or leave donor site open and harvesting technique are some of
      the factors suggested to account for differences in donor site morbidity.
      CONCLUSION: Oral mucosal graft is a versatile urethral substitute with excellent
      outcome. It is becoming the gold standard for urethral substitution.

PMID- 20139541
TI  - Awareness and knowledge of mother-to-child transmission of HIV among mothers
      attending the pediatric HIV clinic, Kano, Nigeria.
AB  - BACKGROUND: Nigeria accounts for about 10% of all HIV/AIDS cases in the world.
      Globally women constitute 48% of adults infected with HIV; in Nigeria, they
      constitute 57%. There is an increase in the number of children infected with HIV
      in recent years as the number of HIV-positive women has increased. However, more
      than 90% of HIV infections in children aged less than 15 years are due to mother
      to-child transmission of HIV. OBJECTIVE: To evaluate the awareness and knowledge
      of mother-to-child transmission of HIV, HIV/AIDS and the methods to prevent
      mother-to-child transmission of HIV. METHODS: This is a descriptive study. The
      study was carried out at the pediatric HIV clinic of Aminu Kano Teaching Hospital
      from 1 st July 2006 to 30 th December 2006. Mothers included in the study were
      mothers in first contact with HIV facilities, which was at our center, before any
      form of counseling. The instrument used was a questionnaire designed to assess
      awareness of the mothers about HIV/AIDS, evaluate their knowledge of possible
      routes of transmission and measures to prevent vertical transmission. The
      questionnaire was then pre-tested for comprehensibility, appropriateness of
      language, sensitivity of questions and average duration of administration.
      RESULTS: A total of 164 mothers brought their children for treatment to the
      pediatric HIV clinic. The level of awareness about HIV/AIDS among mothers was
      very high (100%), and the main sources of information were radio (48.8%) and
      television (37.8%). Ninety-one percent of mothers were aware of mother-to-child
      transmission of HIV. Transplacental route (41%) was the commonly identified route
      of transmission. The level of knowledge and perceptions of mother-to-child
      transmission of HIV is inadequate. CONCLUSION: There is a need to scale up
      education about mother-to-child transmission of HIV in our health facilities.

PMID- 20139542
TI  - Prevalence and predictors of illicit drug use among school-going adolescents in
      Harare, Zimbabwe.
AB  - OBJECTIVE: To estimate the prevalence and predictors of illicit drug use among
      school-going adolescents in Harare, Zimbabwe. METHODS: We used data from the
      Global School-based Health Survey (GSHS) conducted in 2003 in Harare to obtain
      frequencies of a selected list of characteristics. We also carried out logistic
      regression to assess the association between illicit drug use and explanatory
      variables. For the purpose of this study, illicit drug use was defined as
      marijuana or glue use. RESULTS: A total of 1984 adolescents participated in the
      study. Most of the sample were females (50.7%), 15-year- olds (30.3%), nonsmokers
      and non-alcohol drinkers. Nine percent of the subjects (13.4% males and 4.9%
      females) reported having ever used marijuana or glue. Males were more likely to
      have used marijuana or glue than females (OR=2.70; 95% CI [1.47, 4.96]).
      Marijuana or glue use was positively associated with cigarette smoking (OR=11.17;
      95% CI [4.29, 29.08]), alcohol drinking (OR=7.00; 95% CI [3.39, 14.47]) and
      sexual intercourse (OR=5.17; 95% CI [2.59, 10.29]). Parental supervision was a
      protective factor for marijuana or glue use (OR=0.31; 95% CI [0.16, 0.61]).
      CONCLUSIONS: Public health intervention aimed to prevent marijuana or glue use
      among adolescents should be designed with the understanding that illicit drug use
      may be associated with other behaviors such as teenage sexual activity, cigarette
      smoking and alcohol use.

PMID- 20139543
TI  - Trends in maternal mortality in a tertiary institution in Northern Nigeria.
AB  - OBJECTIVE: To look at the trends in maternal mortality in our institution over 5
      years. METHODS: Records of 112 maternal deaths were retrospectively reviewed to
      determine the trends and the likely direct cause of each death over the study
      period. RESULTS: There were a total of 112 maternal deaths, while 3931 deliveries
      were conducted over the 5-year period. The maternal mortality ratio (MMR) was
      2849/100,000 deliveries. The highest MMR of 6234/100,000 was observed in 2003,
      with remarkable decline to 1837/100,000 in 2007. Eclampsia consistently remained
      the leading cause, accounting for 46.4% of the maternal deaths, followed by
      sepsis and postpartum hemorrhage (PPH) contributing 17% and 14.3%, respectively.
      There were no statistically significant differences in the corresponding
      percentages of maternal deaths between various age groups (chi2=6.68; P =0.083).
      Grandmultiparas accounted for a significant proportion of maternal deaths as
      compared to low parity, with chi2=10.43; P =0.00054. Lack of seeking antenatal
      care (unbooked) and illiteracy were observed to be significant determinants of
      maternal mortality (chi2=64.69, P =0.00000; and chi2=18.52, P =0.0000168,
      respectively). CONCLUSION: In spite of decrease in the maternal mortality ratio
      over the years, it still remains high, with eclampsia persistently contributing
      most significantly. Community enlightenment on the need to avail of antenatal
      care and hospital delivery services, and improvement in the quality of skilled
      maternity care will, among other factors, drastically curtail these preventable
      causes of maternal death and reduce MMR.

PMID- 20139544
TI  - Social marketing potential of qualitative cost-free-to-patient eye care program
      in a Nigerian community.
AB  - BACKGROUND: In 2006, a qualitative, cost-free-to-patient eye care program took
      place in Owo, Nigeria. This study sought to identify factors that are of
      marketing importance in qualitative cost-free-to-patient eye care program.
      METHODS: A cross-sectional survey of postoperative patients using interviewer
      administered questionnaire to probe into patient socio-demographic factors,
      source of awareness about the eye care program, initial perception of the
      program, assessment of the performance of eye care personnel and overall
      assessment of the eye care program was carried out. Comments of patients on
      problems encountered and suggestions from them for improvement were noted.
      RESULTS: Ninety-nine patients comprising of 47 men and 52 women, with age range
      of 24 to 98 years, participated. Factors of marketing importance identified
      included publicity through people (46.5%), town criers (21.2%), radio (15.2%),
      churches (8.1%), mosques (5.1%) and banners (4.0%). Patients' assessment of the
      program was as follows: Service to the community (83%); excellent eye care team
      performance (80%); and overall program rating as follows: Very satisfactory
      (76%), satisfactory (22%). The remarkable problem was long waiting period
      (15.3%). Suggestions of the patients were as follows: Improve program
      sustainability (10.1%); increase eye care manpower (7.1%); and public support for
      the sponsor in order to continue with perceived laudable project 4 (4.0%).
      CONCLUSION: Adequate publicity, patients' good perception, excellent eye care
      team performance and patients' overall satisfaction can create awareness about
      the need to avail of eye care services.

PMID- 20139545
TI  - Associations of advertisement-promotion-sponsorship-related factors with current
      cigarette smoking among in-school adolescents in Zambia.
AB  - BACKGROUND: Tobacco use is the leading cause of noncommunicable disease morbidity
      and mortality. Most smokers initiate the smoking habit as adolescents or young
      adults. METHODS: Survey data from the 2007 Lusaka (Zambia) Global Youth Tobacco
      Survey were used to estimate the prevalence of current cigarette smoking and
      assess whether exposure to pro-tobacco media and perception of the potential harm
      of secondhand smoke are associated with adolescents' smoking. Logistic regression
      analysis was used to estimate the associations. RESULTS: Altogether, 2378
      students, of whom 56.8% were females, participated in the study. Overall, 10.5%
      of the students (9.3% among males and 12.1% among females) smoked cigarettes in
      the 30 days prior to the survey. Students who favored banning smoking in public
      places were 33% (OR = 0.67; 95% CI [0.47, 0.96]) less likely to smoke cigarettes
      compared to those who were not in favor of the ban. Seeing actors smoking in TV
      shows, videos or movies was positively associated with smoking (OR = 1.90; 95% CI
      [1.26, 2.88]). However, possessing an item with a cigarette brand logo on it,
      seeing advertisements of cigarettes on billboards and being ever offered a free
      cigarette by a cigarette sales representative were negatively associated with
      smoking (OR=0.39, 95% CI [0.26, 0.58]; OR=0.63, 95% CI [0.43, 0.92]; and OR=0.43,
      95% CI [0.29, 0.65], respectively). CONCLUSION: Findings from this study indicate
      that TV advertisement-promotion-sponsorship was positively associated with
      smoking, while it was the opposite with other forms of advertisement; there is a
      need for further studies.

PMID- 20139546
TI  - The range of abdominal surgical emergencies in children older than 1 year at the
      Komfo Anokye Teaching Hospital, Kumasi, Ghana.
AB  - BACKGROUND: Acute abdominal conditions are a common reason for emergency
      admission of children. Little is available in the literature about such
      conditions in our subregion, especially Ghana. OBJECTIVE: The aim of this study
      was to investigate the range of emergency abdominal surgical conditions amongst
      children in the subregion, with particular reference to Komfo Anokye Teaching
      Hospital, Kumasi, Ghana. A prospective survey of all children older than 1 year
      undergoing an emergency abdominal surgery was carried out. METHODS: Details of
      all children (except infants) operated for an acute surgical abdominal condition
      over a 5-year period were entered into a specially designed form, capturing
      patient characteristics, surgical causes of the emergency, operative procedure,
      complications, morbidity and mortality rates. RESULTS: Nine hundred fifty-five
      children aged > 1 year but < 15 years were enrolled in the study. The mean age
      was 8.8 +/- 3.2 years. The leading causes of surgical abdominal emergencies were
      typhoid perforation (TP) of the gastrointestinal tract (GIT), 68%; acute
      appendicitis, 16%; abdominal trauma and intestinal obstruction (including
      intussusception), 4.7% each; irreducible external hernias, 2.5%; primary
      peritonitis, 1.0%; gallbladder disease and gastric perforation, 0.8% each. Many
      children died from the TP group; case fatality for TP alone was 12.6%. The
      overall mortality was 9.7%. Morbidity was influenced by the presence of major
      peritoneal contamination, continuing peritonitis and surgical site infections
      (SSIs), which led to long hospital stay. CONCLUSIONS: In our hospital, TP of the
      GIT, acute appendicitis, intestinal obstruction, irreducible external hernias and
      primary peritonitis were the most common abdominal emergencies encountered in
      children after infancy. The high morbidity and mortality in TP is attributable to
      ignorance, poor sanitation and delay in reporting to hospital for treatment.

PMID- 20139547
TI  - Perceptions of working conditions amongst health workers in state-owned
      facilities in northeastern Nigeria.
AB  - BACKGROUND: The health care sector depends to a large extent on human labor. Poor
      worker motivation can greatly affect health outcomes and patient safety. There is
      little information on the health workers' perceptions of working conditions in
      resource-poor settings. METHOD: Three state-owned facilities in each state were
      selected by simple random sampling technique. The selected facilities were
      visited on weekdays between 9 and 10 a.m. A self-administered structured
      questionnaire was given to all health care workers on duty in the facility at the
      time of visit. RESULTS: A total of 299 questionnaires were returned. The response
      rate was 85.43%. Two hundred four (68.2%) workers experienced general
      satisfaction with their current jobs. The relationships between general job
      satisfaction and presence of conflict at work (P = 0.001), freedom of expression
      (P > 0.001), managerial support for staff welfare (P > 0.001), managerial support
      for staff career development (P > 0.001), availability of tools and consumables
      in the workplace (P > 0.001) and progress towards personal professional goals (P
      = 0.001) were statistically significant. CONCLUSION: The level of general job
      satisfaction was high. Though salaries were important, presence of conflict at
      work, freedom of expression, managerial support for staff welfare, managerial
      support for staff career development, availability of tools and consumables in
      the workplace and progress towards personal professional goals appear to play a
      role in worker motivation.

PMID- 20139548
TI  - Epidural anesthesia: views and outcomes of women in labor in a Nigerian hospital.
AB  - BACKGROUND: Pain during childbirth is a well known cause of dissatisfaction
      amongst women in labor. The use of epidural analgesia in labor is becoming
      widespread due to its benefit in terms of pain relief. METHOD: After approval of
      the local Ethics Committee on Research and obtaining informed written consent, 50
      American Society of Anesthesiologists (ASA) class I-II consecutive multiparous
      women in labor requesting pain relief were enrolled in this prospective study.
      After providing description of the two options of pain relief available to them,
      they were allocated into two groups according to their request-to receive either
      parenteral opioid/sedative or epidural labor analgesia. Both groups received
      analgesia of choice at 4-cm cervical os dilatation. The epidural group received
      0.125% plain bupivacaine, while the other group received pentazocine/promethazine
      intravenously. The time taken to locate the epidural space, catheter-related
      complications encountered and the amount of intravenous fluid used were
      documented. RESULT: The two groups were comparable in terms of socio-demographic
      data. The mean duration of the first and second stages of labor, respectively,
      were significantly shorter in the epidural group when compared with those in the
      non-epidural group ([P < 0.01] and [P < 0.02]). There was no difference in the
      rate of cesarean delivery between them - epidural analgesia (32% [8/25]) versus
      parenteral opioid/sedative (44% [11/25]), (OR, 0.60; 95% CI, 0.19-1.90). The
      maternal blood loss from delivery was minimal, with no statistical difference
      between the two groups (P = 0.27). The neonatal outcome was the same in both
      groups. Closed questionnaire showed that the overall experience of labor was much
      better (it was also better than expected) in the epidural group when compared
      with that in the non-epidural group (80% versus 4%). Eighteen (72%) women had
      inadequate pain relief in the non-epidural group as compared to 2 (8%) women in
      the epidural group. CONCLUSION: The study shows that epidural labor analgesia is
      acceptable to women in our setting. More women in the epidural analgesia group
      were satisfied with the experience of labor than those who did not receive this
      form of analgesia than among those who received parenteral opioid/sedative.

PMID- 20139549
TI  - CD4+ T-lymphocytes cell counts in adults with human immunodeficiency virus
      infection at the medical department of a tertiary health institution in Nigeria.
AB  - OBJECTIVES: To evaluate the CD4+ cell counts in adults with human
      immunodeficiency virus (HIV) infections presenting at the medical department of
      the Federal Medical Centre, Ido-Ekiti, Nigeria. METHODS: This study was carried
      out at the medical department of the Federal Medical Centre (FMC), Ido-Ekiti,
      Nigeria, in the period July-December 2006. FMC, Ido, was recently upgraded to
      serve as the only center for HIV/AIDS referral, diagnosis and treatment in Ekiti
      State. The center offers free antiretroviral therapy. All patients with a
      diagnosis of HIV/AIDS, either diagnosed at the center or referred from other
      hospitals, admitted to the medical department within the study period had their
      blood sample taken for CD4 cell counts estimation at the first visit to the
      center, as part of the routine workup to assess their disease status and need for
      antiretroviral therapy. RESULTS: A total of 87 patients comprising of 54 (62.1%)
      females and 33 (37.9%) males had their CD4+ T-Lymphocytes cell counts evaluated
      within their first week of presentation. The total mean age of the population
      studied was 33.17 +/- 7.01 years. The mean age of the females was 31 +/- 5.6
      years, while that of the males was 36.5 +/- 8.2 years. The difference between the
      mean ages of females and males was statistically significant (P = 0.0004). The
      female: male ratio was 1.6:1. Out of the 87 patients, 30 were referrals from
      other hospitals within the state. The total mean CD4+ cell count was 230.7 +/-
      311.9 cells/microL. The mean CD4 cell count of females was 212.17 +/- 264.96
      cells/microL, while that of males was 261.0 +/- 389.19 cells/microL. This
      difference was not significant (P = 0.4876). Majority of the patients (75,
      [86.2%]), had CD4 cell count < 350 cells/microL, comprising of 48 females and 27
      males. Of the 75 patients, 57 (76%) had a CD4 cell count < 200 cells/microL (33
      females vs. 24 males). CONCLUSION: At the time of HIV diagnosis, majority of our
      patients had a CD4+ cell count < 200 cells/microL. This was consistent with a
      relatively advanced disease. More women than men in the population were found
      positive for HIV. More sustained and vigorous awareness campaigns need be
      embarked upon in the HIV propaganda in the Ekiti State on one hand and Nigeria on
      the other hand to bring down this Hydra-headed monster called HIV/AIDS.

PMID- 20139550
TI  - Awareness and perception of maternal mortality among women in a semi-urban
      community in the Niger Delta of Nigeria.
AB  - BACKGROUND: Maternal mortality rates are very high in Nigeria. Increased level of
      awareness and perception will reduce maternal mortality rates. OBJECTIVE: The
      study was aimed at assessing the awareness and perception of maternal mortality
      among women in the reproductive age group at Ogunu community in Warri South Local
      Government Area of Delta State. METHODOLOGY: This was a descriptive cross
      sectional study that was carried out in Ogunu town in Delta State. A simple
      random sampling technique was used to select 400 women, who gave consent to be
      enrolled in the study. They were assisted in filling a semi-structured
      questionnaire containing questions on awareness and perception of maternal
      mortality among women in the community. Information generated was recorded on a
      data collection sheet designed for the study. The coded data were fed into the
      computer using the SPSS program to determine the mean values and frequencies.
      RESULTS: A total of 400 questionnaires were distributed; of these, 349 were
      completely filled and returned. The mean age of the study subjects was 31.6 +/-
      7.7 years. Among these subjects, 54.7% were married, while 32.7%, 28.7% and 26.5%
      had tertiary, secondary and primary education, respectively. The study revealed
      that 96.3% of the subjects felt that death can occur from pregnancy-related
      problems, while 69.1% were aware of maternal mortality. Majority of the subjects
      agreed that one or more forms of delay could be responsible for their death. This
      study shows that a good proportion of subjects was aware of maternal mortality
      and also had a good perception of it. CONCLUSION: Efforts should be directed
      towards educating women about the risk of delivering in homes of traditional
      birth attendants, maternity homes and health centers, and the concept of early
      referral of women to the hospital should be reinforced. Providing information to
      women on prevention of maternal mortality and community participation and
      mobilization will help prevent maternal mortality to some extent in Nigeria.

PMID- 20139551
TI  - Circumcision mishaps in Nigerian children.
AB  - BACKGROUND/OBJECTIVE: Circumcision may be associated with complications which are
      usually minor but could be life threatening on certain occasions. This study
      determined contributory factors, pattern of presentation, challenges of
      management and outcome of circumcision mishaps in Benin City, Nigeria. METHODS: A
      retrospective analysis of all male children managed for circumcision mishaps
      between January 1998 and December 2007 at the University of Benin Teaching
      Hospital, Benin City, Nigeria. RESULTS: There were 346 male children aged between
      6 days and 12 years. Period of presentation to the unit ranged between 1 hour and
      12 years. Redundant prepuce, 51 (14.7%); glandulopenile adhesions, 30 (8.7%);
      implantation cyst, 10 (2.9%); penile chordee, 11 (3.2%); local wound infection,
      17 (4.9%); and proximal migration of plastibell ring, 11 (3.2%), were common
      mishaps treated with good outcome. On the other hand, urethrocutaneous fistula,
      73 (21.1%); hemorrhage, 46 (13.3%); glandular amputation, 9 (2.6%); penile tissue
      avulsion, 24 (7.0%); and transmission of infections, 4 (1.2%), were challenging
      mishaps to manage. These resulted in 18 children with residual penile deformity
      and 4 deaths. Challenging mishaps and late referrals were common among children
      circumcised by traditional circumcisionists (P < 0.0001). Inadequate training of
      circumcisionists; circumcision in unhygienic environment; circumcision with
      unsterilized instruments; circumcision without the use of anesthesia, analgesia
      and antibiotics - which were compounded by late referrals - influenced the
      development and final outcome of circumcision mishaps. CONCLUSION: Circumcision
      mishaps presenting very late with resultant poor outcome are still common in our
      setting. Hospital circumcision by experts, health awareness campaigns, adequate
      training of circumcisionists and early referrals of affected children should be
      encouraged.

PMID- 20139552
TI  - Pattern and outcome of diabetic admissions at a federal medical center: a 5-year
      review.
AB  - BACKGROUND: Prevalence of diabetes mellitus (DM) is increasing worldwide, with
      the major increases expected to occur in developing countries. It has been
      observed that the pattern of hospital admissions can be used to determine the
      effectiveness of outpatient care of DM. OBJECTIVE: This study was aimed to
      examine diabetes-related admissions to medical wards of a federal medical center
      in Ekiti, Nigeria. Such data would be useful to determine the burden on health
      care system and in the planning of appropriate management strategies. METHODS: A
      5-year retrospective analysis of diabetes-related admissions to the medical wards
      of Federal Medical Centre, Ido Ekiti, Ekiti State, between 2003 and 2007 was
      carried out using medical records of the patients. SPSS 13 software was used to
      analyze data. RESULTS: Of the total 2,696 medical admissions, 118 (4.4%) were
      diabetes related. The mean age of these patients was 57 +/- 16.2 years. Majority
      (37.29%) of the patients were admitted for diabetic foot ulcer. Other major
      reasons for admission were severe hypertension (13.56%), uncontrolled
      hyperglycemia (13.56%), hyperglycemic emergencies (11.86%) and stroke (10.17%).
      Duration of hospital stay ranged from 1 to 107 days, with a mean duration of 17.5
      +/- 9.2 days. Mean duration of hospital stay was the longest (25.3 +/- 23.9 days)
      for those admitted for diabetic foot ulcer. Most (74.6%) of the patients were
      discharged and only 4 (3.4%) died. Majority of those who left against medical
      advice were admitted for diabetic foot ulcer. CONCLUSION: There is a need to
      emphasize foot care as one of the cardinal features of optimal diabetes care.
      Establishing clinics specializing in treating diabetes and having facilities for
      treatment of all aspects of diabetes, including diabetic complications, will help
      in providing better patient care and in minimizing hospital admissions.

PMID- 20139553
TI  - Trainee ophthalmologists' opinions on ways to improve cataract surgical rate.
AB  - OBJECTIVE: To know the opinions of trainee ophthalmologists on ways to improve
      cataract surgical rate (CSR) with a view to having insight into actions that
      should be of high priority for achieving this improvement. METHODS: A survey of
      27 trainee ophthalmologists using structured self-administered questionnaire.
      RESULTS: Most trainees had a positive view about actions towards raising CSR:
      Structured ophthalmic training- 25 (92.6%), monthly cataract camps by eye
      departments in teaching hospitals- 21 (77.8%), rural allowance for
      ophthalmologists- 26 (96.3%) and welfare package for indigent cataract patients-
      21 (77.8%). Other actions included local production of cataract consumables- 22
      (81.5%), duty-free importation of ophthalmic materials- 23 (85.2%), employment of
      ophthalmologists in the services of the state governments- 24 (88.9%) and local
      governments- 20 (74.1%), effective primary eye care- 25 (92.6%) and marketing of
      cataract surgical services- 23 (85.2%). However, only 16 (59.3%) trainees wanted
      first ladies (wives of the president, governors and local government chairmen) to
      adopt cataract elimination as pet projects, and 24 (88.9%) opposed the
      introduction of cataract surgeons. CONCLUSION: Most trainees had positive
      perceptions about most actions that can raise CSR. However, top-priority actions
      to improve CSR were attractive rural allowance, structured training, resource
      availability, cost reduction and marketing of cataract surgical services.
      Multiple actions might be necessary to raise CSR.

PMID- 20139554
TI  - Outcome of grommet tube insertions among adult Nigerians with serous otitis
      media.

PMID- 20139555
TI  - Audit of emergency throughput of a plastic surgery unit in a developing country.

PMID- 20139556
TI  - Hepatocellular carcinoma in pregnancy.

PMID- 20139557
TI  - Continuing dental education.

PMID- 20139558
TI  - SEM evaluation of marginal sealing on composite restorations using different
      photoactivation and composite insertion methods.
AB  - AIM: This in vitro study evaluates the influence of marginal sealing methods in
      composite restorations with different adhesive systems submitted to mechanical
      load. MATERIALS AND METHODS: Eighty bovine incisor crowns were embedded in
      Polyvinyl chloride (PVC) molds with the buccal surface exposed, where cavities
      (4mm x 4mm x 3mm) were made. Samples had the adhesive systems, Single Bond or
      Clearfil SE Bond, applied according to the manufacturer's recommendations. The
      cavities were filled with a Z-250 composite according to the restoration
      technique (bulk filling or three increments) and photoactivation (conventional,
      soft start, pulsatile light or light-emitting diode [LED]). The samples were
      duplicated with epoxy resin for scanning electron microscopy observations.
      Samples were also submitted to mechanical load (200,000 cycles; 2 Hz) and new
      replicas were made. RESULTS: The results, in percentages, were submitted to ANOVA
      followed by Tukey's test (P < 0.05). There was statistical difference between the
      cycle group (23.84%) and the non cycle group (18.63%). Comparing the restoration
      technique, there was no statistical difference between bulk filling (19.62%) and
      three increments (22.84%). There was no statistical difference among the groups:
      Pulsatile light (24.38%), soft start (22.75%), LED (21.47%) or conventional
      (16.34%). Furthermore, there were no statistical differences between the adhesive
      systems: Clearfil SE Bond (21.32%) and Single Bond (20.83%). CONCLUSIONS: The
      photoactivation methods, the restorative techniques and the adhesive systems did
      not influence gap formation.

PMID- 20139559
TI  - Canal-centring ability of three rotary file systems in simulated curved canals: a
      comparative study.
AB  - OBJECTIVE: To compare the canal-centring ability of M two , ProFile and RaCe
      rotary files, in simulated curved canals. MATERIALS AND METHODS: About 30
      simulated canals were prepared by M two , ProFile and RaCe rotary files. Pre and
      post-operative pictures were super-imposed and transportations recorded.
      Measurements were carried out at five different points: Canal orifice (O); half
      way to the orifice in the straight section (HO); the beginning of the curve (BC);
      the apex of the curve (AC); the end point (EP). Intra- and inter-group
      comparisons were carried out by Wilcoxon;s signed ranks test and Kruskal-Wallis
      test respectively, using SPSS 14.0 software. RESULTS: ProFile did not change
      canal centricity in any point. RaCe kept centricity at HO, BC, AC and EP. M two
      changed canal centricity in points BC, AC and EP. M two group kept the centricity
      significantly less than the other two groups at BC (P = 0.004), AC (P = 0.015)
      and EP (P = 0.01). There was no significant difference between these three rotary
      files at HO. However, the difference between RaCe, M two and ProFile was
      significant at O (P = 0.015). CONCLUSION: ProFile and RaCe rotary files remained
      better centred than M two rotary files.

PMID- 20139560
TI  - Effect of a single-use toothbrush on plaque microflora.
AB  - AIM: To study and compare the microbial flora of dental plaque after the use of a
      self-contaminated toothbrush and that of a single-use toothbrush. MATERIALS AND
      METHODS: The study group included 40 young volunteers from Yenepoya Dental
      College, who were free from any systemic or oral disease. In these subjects,
      plaque samples were collected after 1 month use of a self-contaminated
      toothbrush. Each subject was given a set of 30 new toothbrushes and a toothpaste
      tube and instructed to use one toothbrush everyday and discard it after use. The
      plaque samples were collected on a weekly interval and cultured on Mitis
      Salivarius agar. The colonies were identified and speciated and their count was
      recorded. RESULTS: Streptococcus mitis, S. mutans, S. sanguis, S. milleri and
      Candida were recovered from the samples. A highly significant decrease in their
      numbers was found after the use of a single-use toothbrush (P value 0.001).
      CONCLUSIONS: As a contaminated toothbrush can reintroduce microorganisms into the
      oral cavity, it may be a sound practice to change the toothbrush as frequently as
      possible.

PMID- 20139561
TI  - Correlation of " in vivo" microcirculation and degeneration of the basal cells of
      the epithelium in lingual lichen planus.
AB  - BACKGROUND: Oral lichen planus is an inflammatory chronic disease with an
      autimmune pathogenesis and unknown etiology that affects oral mucosa, with or
      without the involvement of the skin and other mucous membranes. The principal
      histological characteristics are the degeneration of the basal cell layer and the
      abnormal infiltration of inflammatory cells into the subepithelial layer of
      connective tissue. OBJECTIVES: This study is aimed to appraise if lingual lichen
      planus (LLP) is sustained by alteration of the oral microcirculation and if this
      abnormal vascularisation increases the degeneration of basal keratinocytes and
      the disruption of the basement membrane. MATERIALS AND METHODS: Fifteen patients
      with a histological diagnosis of LLP with higher degree of degeneration of the
      basement membrane, fifteen LLP patients with lower degree of basement membrane
      (BM) degeneration and fifteen healthy patients were included in the study. The
      microcirculation of the left margin of the lingual mucosa of all the patients and
      subjects was analysed with the videocapillaroscopy. The following parameters were
      analyzed on each capillaroscopic image: c0 apillary loop length, loop diameter,
      and capillary density. The results obtained by videocapillaroscopy software were
      subjected to statistical analysis using Mann Whitney U-test (P < 0.001).
      Statistical analysis was performed using PAST software, v. 1.53. RESULTS:
      Capillary density, loop length, and total diameter showed statistically
      significant differences between LLP patients with histologically lower degree of
      BM degeneration and healthy subjects and a meaningful significant difference
      between LLP patients with higher degree of BM degeneration. CONCLUSIONS: A
      remarkable increase in capillary density was showed by videocapillaroscopic exam.
      The increased value of the density could be associated with angiogenesis
      mechanism and it could be an indicator of the evolutionary condition of LLP.
      Videocapillaroscopy may be useful for the evaluation of the evolution or
      regression of the disease.

PMID- 20139562
TI  - A comparative study of inter-abutment distance of dies made from full arch dual
      arch impression trays with those made from full arch stock trays: an in vitro
      study.
AB  - OBJECTIVES: The dual-arch impression technique is convenient in that it makes the
      required maxillary and mandibular impressions, as well as the inter-occlusal
      record in one procedure. The accuracy of inter-abutment distance in dies
      fabricated from dual-arch impression technique remains in question because there
      is little information available in the literature. MATERIALS AND METHODS: This
      study was conducted to evaluate the accuracy of inter-abutment distance in dies
      obtained from full arch dual-arch trays with those obtained from full arch stock
      metal trays. RESULTS AND CONCLUSION: The metal dual-arch trays showed better
      accuracy followed by the plastic dual-arch and stock dentulous trays,
      respectively, though statistically insignificant. The pouring sequence did not
      have any effect on the inter-abutment distance statistically, though pouring the
      non-working side of the dual-arch impression first showed better accuracy.

PMID- 20139563
TI  - Evaluation of gastric tolerability, antinociceptive and antiinflammatory activity
      of combination NSAIDs in rats.
AB  - BACKGROUND: Non-steroidal antiinflammatory drugs (NSAIDs) are one of the most
      commonly prescribed drugs in clinical practice. Presently, several varieties of
      fixed dose combinations (FDCs) of NSAIDs are available over the counter and are
      being prescribed too. There is paucity of literature regarding comparative
      efficacy of these combinations against their individual component. Various
      clinical studies have documented increased incidence of gastric ulcerations with
      usage of more than one NSAID simultaneously. OBJECTIVES: To study gastric
      tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs
      in rats. MATERIALS AND METHODS: Gastric tolerability of different NSAIDs was
      observed after administration of drugs for 7 days orally. On 7 th day, 4 h after
      drug administration, rats were sacrificed and stomach mucosa was examined for
      ulcerations. Analgesic or antinociceptive activity of single and combination
      NSAIDs was evaluated using Writhing test model. For induction of writhing, 4%
      normal saline (hypertonic saline) was injected (0.1 ml/10 gm) intraperitoneally.
      Evaluation of antiinflammatory activity for FDCs of NSAIDs was done by using rat
      paw edema model with the aid of plethysmometer. Paw edema was induced by
      injecting 0.1 ml of 1% formalin in sub-planter region of hind paw. RESULTS:
      Analgesic activity was found to be enhanced or significant only in the group
      pretreated with combination of nimesulide with ibuprofen as compared to ibuprofen
      alone group (P = 0.01). Decrease in mean paw edema (antiinflammatory activity)
      was not significant in rats pretreated with combination NSAIDs as compared to
      NSAID-alone group. Mean gastric ulcer index was significant in groups pretreated
      with diclofenac alone (P = 0.03) and in combination groups of nimesulide with
      diclofenac and ibuprofen with paracetamol as compared to control (P = 0.03, P =
      0.007). CONCLUSION: Addition of ibuprofen to paracetamol and combining diclofenac
      to nimesulide, significantly increased severity of gastric ulcerations. Fixed
      dose combination does not possess additional analgesic activity over their
      individual components, only exception being combination of nimesulide with
      ibuprofen, which has additional analgesic activity over ibuprofen alone, and this
      combination was not found to be ulcerogenic. Antiinflammatory activity of
      ibuprofen, paracetamol and nimesulide was significantly enhanced after addition
      of diclofenac.

PMID- 20139564
TI  - Community periodontal index of treatment needs index: an indicator of anaerobic
      periodontal infection.
AB  - BACKGROUND: Community periodontal index of treatment needs (CPITN) index is
      commonly used to measure periodontal disease. It's uniqueness, apart from
      assessing the periodontal status, also gives the treatment needs for the
      underlying condition. Benzoyl-DL-arginine napthylamide (BANA) test is a chair
      side diagnostic test used to detect the presence of putative periodontal
      pathogens. We correlated the CPITN scores of patients with BANA test results to
      assess the validity of CPITN as an indicator of anaerobic periodontal infection.
      OBJECTIVES: The present study was aimed to correlate the CPITN scores with the
      BANA activity of subgingival plaque. The objective was to assess the validity of
      CPITN index as indicator of anaerobic periodontal infection. PATIENTS AND
      METHODS: A total of 80 sites were selected from 20 patients with generalized
      chronic periodontitis. After measuring the probing depth with CPITN C probe, the
      highest score from each sextant was selected according to the CPITN criteria and
      subgingival plaque samples were collected using a sterile curette and the BANA
      test was performed. RESULTS: Kendall's tau-b and Chi-square test were used to
      assess the correlation between the BANA test results and CPITN scores. Results
      indicated sensitivity (92.86%), specificity (80%) and agreement (91.25%);
      indicating the validity of CPITN in assessing anaerobic infection. CONCLUSION:
      There was a significant correlation between BANA test results and scores 3 and
      score 4 of CPITN index (P < 0.001) clearly indicating the presence of anaerobic
      periodontal infection.

PMID- 20139565
TI  - Relationship between the size of patency file and apical extrusion of sodium
      hypochlorite.
AB  - BACKGROUND: Sodium hypochlorite (NaOCl) is the most widely used endodontic
      irrigant because of its excellent antimicrobial, organic tissue dissolving, and
      lubricating properties. However, it is highly cytotoxic to the periapical
      tissues. AIM: This study evaluated in vitro the extrusion of 5.25% NaOCl through
      the apical foramina of mesiobuccal (MB) root canals of maxillary first molars in
      two experimental conditions: Before apical debridement and after apical
      debridement with different instrument sizes to ensure direct access to the apical
      foramen (apical patency). MATERIALS AND METHODS: Coronal accesses were prepared
      in 17 teeth and the apical foramina of the distobuccal and palatal root canals
      were sealed. The teeth were held in acrylic receptacles with the roots turned
      upwards to reproduce their position in the maxillary dental arch. The receptacles
      were filled with a starch/KI solution (a reagent that changes its color to blue
      after contacting NaOCl) covering the roots. The experiment had two phases: P1:
      Irrigation of the MB canals with 5.25% NaOCl without previous establishment of
      apical patency; P2: Canal irrigation after use of size 10 K-file and size 15
      Flexofile as patency files. Only specimens with no NaOCl extrusion in P1 were
      assigned to P2. NaOCl was delivered pressureless at the canal entrance. The
      moment that the starch/KI solution contacted NaOCl was captured on digital
      photographs. RESULTS AND CONCLUSIONS: There was no NaOCl extrusion in nine
      specimens in P1, but all of these teeth had irrigant extrusion in P2. The 5.25%
      NaOCl used as an endodontic irrigant showed great capacity to extrude beyond both
      intact and small-sized apical foramina of MB root canals of maxillary first
      molars.

PMID- 20139566
TI  - Effect of water storage on resin-dentin bond strengths formed by different
      bonding approaches.
AB  - OBJECTIVES: The purpose of this study was to evaluate the influence of water
      storage on resin-dentin bond strengths [microTBS] using different adhesive
      bonding approaches. MATERIALS AND METHODS: Flat superficial dentin surfaces of 24
      extracted human third molars were exposed and polished to create a standardized
      smear layer. The teeth were randomly distributed into four different groups:
      Three-step etch-and-rinse (Adper Scotchbond Multi-Purpose, 3M ESPE-SBMP), two
      step etch-and-rinse (Adper Single Bond 2, 3 M ESPE-SB); two-step self-etch
      (AdheSE, Ivoclar/Vivadent-AD); and self-etch 1 step (Adper Prompt L-Pop, 3M ESPE
      LP). Following the adhesive application (n = 6), resin composite was
      incrementally applied (Filtek Supreme XT-3 M ESPE) in order to obtain bonded
      sticks, with a cross-sectioned area of 0.81 mm2. The bonded sticks were randomly
      divided and assigned to be tested after one day [OD] (n 30) or six months [6 M]
      of water storage [6 M] (n = 30). RESULTS: Two-way ANOVA and Tukey's test showed
      that none of the adhesives showed degradation after 6 M. SB achieved the highest
      microTBS both in the [OD] (49.13 MPa) and [6M] (40.27 MPa). Despite the highest
      values in both time evaluations, the microTBS of SB significantly reduced after
      6M. LP showed the lowest microTBS in both periods of evaluation (18.35 and 18.34
      MPa). CONCLUSIONS: Although a significant degradation was only observed for SB,
      this was the adhesive that showed the highest microTBS after 6 M of water
      storage.

PMID- 20139567
TI  - In vitro evaluation of force-expansion characteristics in a newly designed
      orthodontic expansion screw compared to conventional screws.
AB  - OBJECTIVE: Expansion screws like Hyrax, Haas and other types, produce heavy
      interrupted forces which are unfavorable for dental movement and could be harmful
      to the tooth and periodontium. The other disadvantage of these screws is the need
      for patient cooperation for their regular activation. The purpose of this study
      was to design a screw and compare its force- expansion curve with other types.
      MATERIALS AND METHODS: A new screw was designed and fabricated in the same
      dimension, with conventional types, with the ability of 8 mm expansion (Free wire
      length: 12 mm, initial compression: 4.5 mm, spring wire diameter: 0.4 mm, spring
      diameter: 3 mm, number of the coils: n0 ine, material: s0 tainless steel). In
      this in vitro study, the new screw was placed in an acrylic orthodontic
      appliance, and after mounting on a stone cast, the force-expansion curve was
      evaluated by a compression test machine and compared to other screws. RESULTS:
      Force-expansion curve of designed screw had a flatter inclination compared to
      other screws. Generally it produced a light continuous force (two to 3.5 pounds)
      for every 4 mm of expansion. CONCLUSION: In comparison with heavy and interrupted
      forces of other screws, the newly designed screw created light and continuous
      forces.

PMID- 20139568
TI  - Effects of platelet-rich plasma on healing of alveolar socket: split-mouth
      histological and histometric evaluation in Cebus apella monkeys.
AB  - CONTEXT: The prediction of implant treatment is directly influenced by the
      quality of the remaining bone after tooth extraction. AIMS: The purpose of this
      experimental study was to, histologically and histometrically, evaluate the bone
      repair process in the central areas of extraction sockets filled with platelet
      rich plasma. MATERIALS AND METHODS: Four young adult male Cebus apella monkeys
      were used. The extraction of both right and left inferior second premolars was
      accomplished. After extraction, in one of the extraction sockets, coagulum was
      maintained while in the other it was removed; the alveolus was dried with gauze
      compress and filled up with platelet concentrate. For PRP production,
      Sonnleitner's protocol was followed. The specimens for histological and
      histometric assessment were obtained in 30, 90, 120 and 180 days intervals.
      RESULTS: In 30 days new bone formation was intense in both experimental and
      control sockets and no significant differences were observed between the two
      groups. After 90 days of the extraction, while the control group showed signs of
      decrease in osteogenesis, in the experimental unit, the process of bone formation
      and fibroblast-like cell proliferation remained intense. After 120 days, the PRP
      treated socket was occupied by large trabeculae of bone. After 180 days, the
      control unit was occupied mostly with bone marrow. The experimental unit remained
      occupied with large amounts of bone tissue. CONCLUSIONS: It was possible to
      conclude that bone repair was enhanced by the use of platelet- rich plasma in
      alveolar sockets.

PMID- 20139569
TI  - A comparative evaluation of metallurgical properties of stainless steel and TMA
      archwires with timolium and titanium niobium archwires--an in vitro study.
AB  - OBJECTIVES: This study aims to evaluate and compare the mechanical and
      metallurgical properties of stainless steel and titanium molybdenum alloy (TMA)
      archwires, with recently introduced timolium and titanium niobium arch wires.
      MATERIALS AND METHODS: Archwires were categorized into four groups (group I to
      IV) with 10 samples in each group. They were evaluated for tensile strength,
      yield strength, modulus of elasticity, load deflection, frictional properties and
      weld characteristics. RESULTS: The results were statistically analyzed using
      ANOVA test and it indicated that stainless steel has high strength, high
      stiffness and low friction compared to other arch wires, thereby proving that it
      is the best choice for both sliding as well as frictionless retraction mechanics.
      TMA with its high formability, low stiffness and low load deflection property is
      suited to apply consistent force in malaligned teeth but, high friction limits
      its use in retraction only with loop mechanics. CONCLUSION: Timolium possesses
      comparatively low stiffness, better strength and behaves as an intermediate
      between stainless steel and TMA and hence can be tried for almost all clinical
      situations. Low springback and high formability of titanium-niobium archwire
      allows creation of finishing bends and thus it can be used as finishing archwire.

PMID- 20139570
TI  - Comparative reliability of cheiloscopy and palatoscopy in human identification.
AB  - BACKGROUND: Establishing a person's identity in postmortem scenarios can be a
      very difficult process. Dental records, fingerprint and DNA comparisons are
      probably the most common techniques used in this context, allowing fast and
      reliable identification processes. However, under certain circumstances they
      cannot always be used; sometimes it is necessary to apply different and less
      known techniques. In forensic identification, lip prints and palatal rugae
      patterns can lead us to important information and help in a person's
      identification. This study aims to ascertain the use of lip prints and palatal
      rugae pattern in identification and sex differentiation. MATERIALS AND METHODS: A
      total of 100 subjects, 50 males and 50 females were selected from among the
      students of Subharti Dental College, Meerut. The materials used to record lip
      prints were lipstick, bond paper, cellophane tape, a brush for applying the
      lipstick, and a magnifying lens. To study palatal rugae, alginate impressions
      were taken and the dental casts analyzed for their various patterns. RESULTS:
      Statistical analysis (applying Z-test for proportion) showed significant
      difference for type I, I', IV and V lip patterns (P < 0.05) in males and females,
      while no significant difference was observed for the same in the palatal rugae
      patterns (P > 0.05). CONCLUSION: This study not only showed that palatal rugae
      and lip prints are unique to an individual, but also that lip prints is more
      reliable for recognition of the sex of an individual.

PMID- 20139571
TI  - Ultrasonographic evaluation of inflammatory swellings of buccal space.
AB  - OBJECTIVES: The main objective of the study was a) to differentiate cellulitis
      and abscess in buccal space region, b) to study the ultrasonographic anatomy of
      cheek region and c) to investigate the use of ultrasound in the diagnosis of
      inflammatory swellings of cheek region. PATIENTS AND METHODS: The study consisted
      of 25 patients with unilateral buccal space inflammatory swellings of odontogenic
      origin. The contra lateral side was used as control. Toshiba ultrasonographic
      device with a linear array transducer (5-8 MHz) was used. The areas of interest
      were scanned under both transverse and longitudinal sections and were interpreted
      by a single observer. The clinical diagnosis of cellulitis or abscess was
      confirmed by the absence or presence of pus respectively both sonographically and
      by aspiration. Also various anatomical structures present in buccal space were
      studied. RESULTS: Clinically 23 (92%) were diagnosed as buccal space abscess and
      2 (8%) were cellulitis. Ultrasonographically and therapeutically 24 (96%) were
      buccal space abscess and 1 (4%) was cellulits. The sensitivity of clinical
      criteria over ultrasonographic diagnosis was 96% with a specificity of 100%. Also
      the cheek thickness in males and females varied from 8.2 to 17.1 mm with a mean
      of 11.6 mm+/-2.1 (SD) and 8.2 mm to 14.2 mm with a mean of 11+/-1.8 (SD). The
      subcutaneous tissue appeared moderately echogenic, buccinator--highly echogenic,
      deep adipose tissue--less echogenic and parotid duct was appreciated as a thin
      hyperechogenic band crossing the buccinator muscle. Buccal space, masticator
      space and parotid space were appreciated. CONCLUSION: This study supports the
      ultrasonographic method of imaging of orofacial inflammatory swellings with high
      sensitivity and specificity. This imaging modality can also help in aspiration of
      pus in different spaces. We have described the ultrasonographic anatomy of the
      above mentioned spaces which can help a beginner in this field.

PMID- 20139572
TI  - Evaluation of oral health awareness in parents of preschool children.
AB  - OBJECTIVES: Little data are available on the initiative shown by the parents for
      dental health care of their preschool children in India. This study was conducted
      to evaluate the status of oral health awareness in parents of preschool children.
      MATERIALS AND METHODS: A total of 230 preschool children were included in the
      study and their parents were analyzed for their child dental awareness by holding
      free dental checkups and interactive meetings with the help of their respective
      schools. RESULTS AND CONCLUSION: Results revealed that there is a low initiation
      of the parents when oral health care of small children is concerned; however, an
      active collective effort of the school and dental team can make awareness program
      effective.

PMID- 20139573
TI  - Periodontitis as a potential risk factor for chronic obstructive pulmonary
      disease: a retrospective study.
AB  - AIMS AND OBJECTIVES: A relationship between poor periodontal health and
      respiratory disease has been suggested by a number of recent studies. The present
      study was undertaken to evaluate potential association between respiratory
      diseases and periodontal health status and to co-relate the severity of
      periodontal disease with that of chronic obstructive pulmonary disease (COPD).
      MATERIALS AND METHODS: 150 patients of COPD (test group) and 50 Patients without
      COPD (control group) were recruited for the study. Information regarding
      patient's demographic and socioeconomic status and lifestyle (history of smoking)
      were considered in the study. Patients with COPD were grouped into mild, moderate
      and severe category on the basis of Spirometry. Periodontal health was assessed
      by measuring probing pocket depth, Clinical Attachment Loss (CAL) and Oral
      Hygiene Index (OHI). RESULTS: The results showed that the subjects with COPD had
      significantly more mean CAL) and a higher mean OHI than those without COPD. The
      risk for COPD appeared to be significantly elevated when attachment loss was
      found to be severe. A trend was noted in that lung function appeared to diminish
      as the amount of attachment loss increased. CONCLUSION: On the basis of the
      observed results of the study it can be concluded that the risk for COPD appeared
      to be significantly elevated when attachment loss was found to be severe. It is
      conceivable that oral interventions that improve oral health status may prove to
      lower the severity of lung infection in susceptible populations.

PMID- 20139574
TI  - Calcium phosphate cement as a "barrier-graft" for the treatment of human
      periodontal intraosseous defects.
AB  - BACKGROUND: Calcium phosphate cements (CPC) are apparently good candidates for
      periodontal treatment by virtue of their biocompatibility, mouldability and
      osteoconductivity. However, the clinical efficacy in this regard has not been
      established. This study is aimed at the evaluation of the efficacy of a
      formulation of CPC in healing human periodontal intraosseous defects in
      comparison with hydroxyapatite ceramic granules. MATERIALS AND METHODS: In this
      clinical study, 60 patients with periodontal defects were divided into 2 test
      groups and 1 control group. The defect sites in the test groups were repaired
      with CPC and hydroxyapatite ceramic granules (HAG). Debridement alone was given
      in the control group. The progress was assessed at 3, 6, 9 and 12 months
      observation intervals through soft tissue parameters (probing depth, attachment
      level and gingival recession). RESULTS: CPC showed significantly better outcome.
      Probing depth reduction values of CPC, HAG and Control at 6 months were 5.40 +/-
      1.43, 3.75 +/- 1.71 and 2.90 +/- 1.48, and those at 12 months were 6.20 +/- 1.80,
      4.5 +/- 1.91 and 2.95 +/- 1.73. Clinical attachment gain values of CPC, HAG and
      Control at 6 months were 5.15 +/- 1.50, 3.45 +/- 1.96 and 2.25 +/- 1.52, and
      those at 12 months were 5.80 +/- 2.02, 3.55 +/- 2.06 and 2.30 +/- 1.78, In both
      cases the P value was < 0.001 showing high significance. The gingival recession
      over 12 months, for the CPC group is lesser than that in the HAG group and the
      value for the control group is marginally higher than both. Soft-tissue
      measurements were appended by postoperative radiographs and surgical re-entry in
      selected cases. CONCLUSIONS: Calcium phosphate cement is found to be
      significantly better than hydroxyapatite ceramic granules. The material could be
      considered as a "barrier-graft".

PMID- 20139575
TI  - The efficacy of a herbal-based toothpaste in the control of plaque and
      gingivitis: a clinico-biochemical study.
AB  - OBJECTIVE: A double-blinded controlled clinical trial with parallel groups was
      designed to investigate the effectiveness of a herbal-based toothpaste in the
      control of plaque and gingivitis as compared with a conventional dentifrice. The
      efficacy of Colgate Herbal over Colgate tooth paste was assessed in this study.
      MATERIALS AND METHODS: Thirty subjects with gingivitis participated in the study.
      All participants had at least 20 natural teeth with no probing depths greater
      than 3 mm and a plaque index score of 2 or more at baseline. At baseline, the
      clinical parameters like gingival index, plaque index and salivary pH were
      estimated. Paired t-test was used to compare the difference within the groups and
      unpaired t-test was used to compare the difference between the groups at baseline
      and on the 30th day. RESULTS: At the end of the study, there were statistically
      significant reductions in the gingival index and the plaque index scores within
      the test group. However, there were no statistically significant differences
      between the test and the control groups. The salivary pH changes were not
      statistically significant in the test group but were displaced more toward the
      acidic range in the control group. CONCLUSION: It was however concluded that the
      herbal-based toothpaste was as effective as the conventionally formulated
      dentifrice in the control of plaque and gingivitis.

PMID- 20139576
TI  - Prosthetic rehabilitation of patients with microstomia.
AB  - Microstomia is defined as an abnormally small oral orifice which can be due to
      various factors. Microstomia is a definite prosthodontic hindrance to carry out
      the different treatment successfully. To rehabilitate a patient with microstomia,
      successfully, the methods and designs incorporated in the prosthesis have to be
      modified. In the past, various techniques have been tried, incorporating certain
      biological and scientific methods to rehabilitate patients with microstomia. This
      article reviews the previously described treatment modalities in case of patients
      with microstomia.

PMID- 20139577
TI  - Obstructive sleep apnea: clinical and diagnostic features.
AB  - Obstructive sleep apnea (OSA) is an increasingly common disorder. It is
      characterized by frequent episodes of airway obstruction associated with a
      reduced caliber of the upper airway and is vulnerable to further narrowing and
      collapse. Acute and repetitive effects of apnea and hypopnea include oxygen
      desaturation, reduction in intrathoracic pressure, excessive daytime sleepiness,
      impaired executive function and central nervous system arousals. The apnea
      hypopnea index and respiratory distress index help quantify the severity of the
      condition. The condition is associated with several clinical symptoms of which
      daytime sleepiness is considered the cardinal symptom. Obesity is one of the
      major predisposing factors. Three types of apneas have been recognized 
      obstructive, central and mixed; OSA is the commonest. This review will cover
      aspects of their radiologic features, diagnosis and management.

PMID- 20139578
TI  - Fabrication of fixed partial dentures using functionally generated path technique
      and double casting.
AB  - Harmonious occlusion is a critical requirement for successful oral
      rehabilitation. Conventional techniques of construction have been unsuccessful in
      producing a prosthesis that can be inserted without intraoral occlusal
      adjustment. This article discusses the use of functionally generated path
      technique with double casting to fabricate fixed partial dentures. The merits of
      this approach and the technique involved are discussed in detail.

PMID- 20139579
TI  - Phalange metastasis from carcinoma of alveolus.
AB  - Metastatic involvement of a phalanx by head and neck cancers is rare. We report a
      case of a 66-year-old man with squamous cell carcinoma of the alveolus who had no
      residual disease or local recurrence after treatment but presented with
      metastasis to the middle phalanx of the middle finger.

PMID- 20139580
TI  - Sialography: report of 3 cases.
AB  - Salivary gland examination is an important part of oral examination, especially
      because of it's involvement in most of the systemic diseases. Patients most
      commonly seek medical attention when the major salivary glands like parotid and
      submandibular gland become enlarged or painful. The various imaging modalities
      practiced to check the salivary gland disorders include conventional radiography,
      sialography, ultrasonography, computerized tomography, radionuclide imaging and
      magnetic resonance imaging. Sialography is one of the oldest imaging procedures
      and still most commonly practiced, as it is a chair side procedure, simple to
      perform, and cost effective. We report the role of sialography as an adjuvant in
      the diagnosis of bacterial sialadenitis and sialadenosis and as a diagnostic and
      therapeutic aid in a case of juvenile recurrent parotitis.

PMID- 20139581
TI  - A rare case of sarcoid-like reaction of lymph nodes associated with squamous cell
      carcinoma of alveolar mucosa.
AB  - Non-necrotizing granulomas are occasionally seen in patients with certain
      malignant disorders and are termed as "sarcoid-like reaction," which have many
      similarities with sarcoidosis. Sarcoidosis is a multisystem granulomatous disease
      of unknown etiology characterized by organ involvement and interference of organ
      function by granuloma or fibrosis. Sarcoidosis is occasionally found in a variety
      of malignant diseases with an overall incidence of 4.4% in carcinoma patients. We
      present here a rare case of moderately differentiated squamous cell carcinoma of
      alveolar mucosa with regard to mandible associated with sarcoid-like reaction of
      cervical lymph nodes in a female patient in the absence of clinical evidence of
      systemic sarcoidosis. The relevant literature including pathogenesis is also
      discussed.

PMID- 20139582
TI  - Tooth regeneration: current status.
AB  - Regeneration of a functional tooth has the potential to be a promising
      therapeutic strategy. Experiments have shown that with the use of principles of
      bioengineering along with adult stem cells, scaffold material, and signaling
      molecules, tooth regeneration is possible. Research work is in progress on
      creating a viable bioroot with all its support. A new culture needs to be created
      that can possibly provide all the nutrients to the stem cells. With the ongoing
      research, tissue engineering is likely to revolutionize dental health and well
      being of people by regenerating teeth over the next decade.

PMID- 20139583
TI  - Progeria.
AB  - Hutchinson Gilford Progeria Syndrome (HGPS) is a rare, sporadic, autosomal
      dominant syndrome that involves premature ageing and death at early age due to
      myocardial infarction or stroke. A 30-year-old male with clinical and radiologic
      features highly suggestive of HGPS is presented here with description of
      differential diagnosis, dental considerations and review of literature.

PMID- 20139584
TI  - Nanotechnology: role in dental biofilms.
AB  - Biofilms are surface-adherent populations of microorganisms consisting of cells,
      water and extracellular matrix material Nanotechnology is promising field of
      science which can guide our understanding of the role of interspecies interaction
      in the development of biofilm. Streptococcus mutans with other species of
      bacteria has been known to form dental biofilm. The correlation between
      genetically modified bacteria Streptococcus mutans and nanoscale morphology has
      been assessed using AFMi.e atomic force microscopy. Nanotechnology application
      includes 16O/18O reverse proteolytic labeling,use of quantum dots for labeling of
      bacterial cells, selective removal of cariogenic bacteria while preserving the
      normal oral flora and silver antimicrobial nanotechnology against pathogens
      associated with biofilms. The future comprises a mouthwash full of smart
      nanomachines which can allow the harmless flora of mouth to flourish in a healthy
      ecosystem.

PMID- 20139585
TI  - Osteoid osteoma.
AB  - Osteoid osteoma is a benign tumor of the bone which arises from osteoblasts and
      is extremely rare in jaws. Only 15 cases of osteoid osteoma have been reported in
      English-language literature. This case report is presented here due to its
      rarity.

PMID- 20139586
TI  - Copper content of various constituents of betel quid.

PMID- 20139587
TI  - Comment on 'standards on restoratives'.

PMID- 20139588
TI  - Regenerative endodontics: a paradigm shift in dental practice.

PMID- 20139589
TI  - Some aspects of dental care in Russia.

PMID- 20139590
TI  - Dental research: some bitter aspects.....

PMID- 20139591
TI  - The multiplicity of N-glycan structures of bovine milk 18 kda lactophorin (milk
      GlyCAM-1).
AB  - Lactophorin is a heat-stable phosphoglycoprotein, also known as milk
      glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1). Bovine 18 kDa
      lactophorin was purified by heparin affinity chromatography from cow's milk whey.
      Its N-glycans were obtained by proteomic techniques, including two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE), followed by in-gel digestion with
      peptide-N(4)-(N-acetyl-beta-glucosaminyl)-asparagine amidase (PNGase F). The
      released N-glycans were derivatized with 2-aminopryridine (PA) and analyzed by
      matrix-assisted laser desorption ionization quadruple ion trap time of flight
      mass spectrometry (MALDI-QIT-TOF MS). Among the MS analyzed peaks, 15 peaks were
      found to be N-glycan molecules as detected by MS(2) analysis. These glycans
      consisted of mono-sialylated bi-, tri-, and tetra-antennary complex-type N
      glycans carrying Gal-GlcNAc (LacNAc) or GalNAc-GlcNAc (LacdiNAc) with and without
      core-fucose.

PMID- 20139592
TI  - The pathway of leucine to mevalonate in halophilic archaea: efficient
      incorporation of leucine into isoprenoidal lipid with the involvement of
      isovaleryl-CoA dehydrogenase in Halobacterium salinarum.
AB  - The pathway of leucine to mevalonate, which has attracted attention in the study
      of the biosynthesis of isoprenoid in parasitic protozoa and myxobacterium, was
      observed in the biosynthesis of the lipid core in halophilic archaea. The
      involvement of isovaleryl-CoA dehydrogenase was strongly suggested, with
      stereospecific conversion of the diastereotopic methyl group of leucine to
      isoprenoidal lipid.

PMID- 20139593
TI  - Gene cloning, bacterial expression, and purification of a novel rice (Oryza
      sativa L.) ubiquitin-related protein, RURM1.
AB  - A rice ubiquitin-related modifier-1 (Rurm1) gene was cloned and transformed in
      Escherichia coli. We successfully expressed the RURM1 protein as a glutathione S
      transferase (GST)-fusion protein by cultivating the E. coli cells at 16 degrees C
      for 16 h. After cleavage of GST, we obtained a single protein of 12 kDa. This
      protein was identified as the RURM1 protein by western blot analysis.

PMID- 20139594
TI  - Cellulase hyperproducing mutants derived from the fungus Trichoderma reesei
      QM9414 produced large amounts of cellulase at the enzymatic and transcriptional
      levels.
AB  - Cellulase hyperproducing mutants derived from the fungus Trichoderma reesei
      QM9414 were analyzed. They exhibited higher filter-paper degrading activity and a
      lower growth rate than the wild-type QM9414 strain. Transcription of the
      cellobiohydrolase I and endoglucanase I genes in the mutants was also greater
      than that of QM9414, suggesting that cellulase hyperproduction by these mutants
      was regulated at the transcriptional level.

PMID- 20139595
TI  - Cloning of the gene encoding an endo-acting pectate lyase from Streptomyces
      thermocarboxydus.
AB  - An endo-acting family 3 pectate lyase (PL I) gene from Streptomyces
      thermocarboxydus was cloned and expressed in Escherichia coli. The deduced PL I
      sequence had highest similarity to a putative pectate lyase of S. coelicolor.
      Recombinant PL I had significantly lower specific activity, probably a result of
      incorrect folding, as indicated by circular dichroism spectra analysis.

PMID- 20139596
TI  - A novel method of screening cell-cycle blockers as candidates for anti-tumor
      reagents using yeast as a screening tool.
AB  - The mechanisms of eukaryotic cell-cycle regulation are closely linked to cellular
      tumorigenesis. Compounds that affect the cell cycle are good candidates for
      developing anti-tumor drugs. We developed a screening method for cell-cycle
      blockers using a Saccharomyces cerevisiae cdc2-1 rad9Delta strain that can detect
      the activity of substances by cell growth. We performed screening on culture
      broth of various microbes, and identified five compounds, borrelidin,
      mycophenolic acid, UCS15A, copiamycin analog, and fredericamycin A, that were
      known to possess anti-tumor activity. These results indicate that this screening
      method is effective as a first-screening system for anti-tumor agents.

PMID- 20139597
TI  - Insight into the mechanism of the stabilization of moloney murine leukaemia virus
      reverse transcriptase by eliminating RNase H activity.
AB  - We explored the mechanism of the stabilization of Moloney murine leukaemia virus
      reverse transcriptase (MMLV RT) by eliminating RNase H activity. Without the
      template-primer (T/P) poly(rA)-p(dT)(15), the temperature reducing initial
      reverse-transcription activity by 50% over a 10-min incubation of the RNase H
      activity-deficient variant D524A was higher by 3.7 degrees C than that of the
      wild-type enzyme (WT). In the reverse transcription reaction, the K(m) values for
      T/P of WT and D524A were almost the same. These results suggest that elimination
      of RNase H activity enhanced the intrinsic thermal stability of MMLV RT rather
      than its affinity toward T/P.

PMID- 20139598
TI  - Structural changes in cuticles on violin bow hair caused by wear.
AB  - A bow with horse tail hair is used to play the violin. New and worn-out bow hairs
      were observed by atomic force microscopy. The cuticles of the new bow hair were
      already damaged by bleach and delipidation, however the worn-out bow hairs were
      much more damaged and broken off by force, which relates to wearing out.

PMID- 20139599
TI  - The chloride ion is an environmental factor affecting the biosynthesis of
      pyoluteorin and 2,4-diacetylphloroglucinol in Pseudomonas sp. YGJ3.
AB  - The effects of Cl(-) on the antibiotics productivity of Pseudomonas sp. YGJ3 were
      investigated. YGJ3 produced pyoluteorin and 2,4-diacetylphloroglucinol, depending
      on the concentration of Cl(-) in the culture medium. Cl(-) stimulated the
      biosynthesis of pyoluteorin, thereby repressing 2,4-diacetylphloroglucinol
      biosynthesis. The cell-free extract from the bacteria grown without Cl(-) showed
      high activity of monoacetylphloroglucinol acetyltransferase, an essential enzyme
      in 2,4-diacetylphloroglucinol biosynthesis.

PMID- 20139600
TI  - Transient up-regulation of immunity- and apoptosis-related genes in Caco-2 cells
      cocultured with THP-1 cells evaluated by DNA microarray analysis.
AB  - We analyzed changes in gene expression in Caco-2 cells cocultured with THP-1
      cells over time periods of 0, 1, 3, 6, 24, and 48 h using a DNA microarray.
      Differentially expressed genes extracted with maSigPro indicated that an early
      defense response and cell death occured at the same time, causing an inflammatory
      condition.

PMID- 20139601
TI  - Solid state fermentation for extracellular polysaccharide production by
      Lactobacillus confusus with coconut water and sugar cane juice as renewable
      wastes.
AB  - Extracellular polysaccharide (EPS) production by Lactobacillus confusus in liquid
      and solid state fermentation was carried out using coconut water and sugarcane
      juice as renewable wastes. High concentrations of EPS of 62 (sugarcane juice) and
      18 g/l of coconut water were produced in solid state fermentation when nitrogen
      sources were reduced 5-fold from the original medium.

PMID- 20139602
TI  - Identification of novel L-amino acid alpha-ligases through Hidden Markov Model
      based profile analysis.
AB  - L-Amino acid alpha-ligase (Lal), catalyzing the formation of alpha-dipeptides
      from unprotected L-amino acids in an ATP-dependent manner, is used in cost
      effective fermentative production of dipeptides. We searched for novel Lals by in
      silico screening using Hidden Markov Model-based profile analysis, and identified
      five novel Lals that showed low similarity and different substrate specificity
      from known Lals.

PMID- 20139603
TI  - Purification and characterization of alpha-N-acetylgalactosaminidases I and II
      from the starfish Asterina amurensis.
AB  - Two alpha-N-acetylgalactosaminidases, alpha-N-acetylgalactosaminidase (alpha
      GalNAcase) I and II, were purified from the digestive organ of starfish. Purified
      alpha-GalNAcase I and II gave nearly single protein bands on SDS-polyacrylamide
      gel electrophoresis, individually. Even the final preparation of alpha-GalNAcase
      I contained alpha-galactosidase activity, while alpha-GalNAcase II was almost
      free from that activity with p-nitrophenyl and 4-methylumbelliferyl alpha-N
      acetylgalactosaminides as substrates. alpha-GalNAcase I and II both hydrolyzed
      terminal alpha-N-acetylgalactosaminyl linkages of the natural compounds
      investigated: Forssman hapten glycolipid, blood group A active oligosaccharide
      and GalNAc-alpha1-O-serine. On the other hand, oligosaccharides, and glycolipid
      containing alpha-galactosyl terminals were hydrolyzed by alpha-GalNAcase I but
      not by alpha-GalNAcase II. The substrate specificities and other enzymatic
      properties of alpha-GalNAcase I were similar to those of human placental alpha
      GalNAcase, but distinct from alpha-GalNAcase II.

PMID- 20139604
TI  - Expression, purification, and characterization of a recombinant neutral
      ceramidase from Mycobacterium tuberculosis.
AB  - Ceramidase (CDase) catalyzes the hydrolysis of ceramide (Cer) to sphingosine
      (Sph) and fatty acid. We have reported the molecular cloning and preliminary
      characterization of the Mycobacterium CDase (MtCDase) (J. Biol. Chem., 274, 36616
      36622 (1999)). To determine its function further, MtCDase was expressed in
      Escherichia coli and purified by Ni-Sepharose and gelfiltration. The purified
      recombinant enzyme showed a single band and a molecular weight estimated to be 71
      kDa on SDS-PAGE. It had a pH optimum at 8.0-9.0 and quite broad specificity for
      various Cers. Of the Cers of different fatty acid moieties tested, those composed
      of C6-C24 fatty acids were well hydrolyzed, and Cers with mono unsaturated fatty
      acids were much more hydrolyzed than those with saturated fatty acids. Using N
      dodecanoyl-7-nitrobenz-2-oxa-1,3-4-diazole (NBD)-D-erythro-sphingosine (C12-NBD
      Cer) as substrates, the reaction followed normal Michaelis-Menten kinetics. The
      apparent Km and Vmax values for C12-NBD-Cer were 98.7 muM and 21.1 pmol/min
      respectively. The purified enzyme also catalyzed the synthesis of Cer in vitro,
      using NBD-labeled dodecanoic acid and Sph as substrates.

PMID- 20139605
TI  - Protective effects of kaempferol (3,4',5,7-tetrahydroxyflavone) against amyloid
      beta peptide (Abeta)-induced neurotoxicity in ICR mice.
AB  - To determine the effects of kaempferol, rat pheochromocytoma cells (PC12) and
      Institute of Cancer Research (ICR) mice were utilized as neuronal models. Using
      in vitro assays, kaempferol was shown to have protective effects against
      oxidative stress-induced cytotoxicity in PC12 cells. Administration of kaempferol
      also significantly reversed amyloid beta peptide (Abeta)-induced impaired
      performance in a Y-maze test. Taken altogether, the results reported here suggest
      that further investigation is warranted of the influence of kaempferol on
      pathways related to Alzheimer's disease.

PMID- 20139606
TI  - Administration of antibiotics during infancy promoted the development of atopic
      dermatitis-like skin lesions in NC/Nga mice.
AB  - This study aimed to determine whether oral antibiotic administration during
      infancy is associated with the spontaneous development of atopic dermatitis-like
      skin lesions by modulating intestinal microbiota. Female NC/Nga mice at 3 weeks
      of age were orally administered kanamycin or polymyxin B. Clinical symptoms,
      scratching behavior, and serum antibody levels were evaluated. Changes in
      intestinal microbiota were determined by culture-independent analysis and
      cultural analysis. The kanamycin-treated mice showed higher clinical scores and
      scratching frequency than the control mice. IgE levels were significantly higher
      in the kanamycin-treated mice than in the control mice. Transient changes in
      intestinal microbiota were observed under kanamycin treatment. Polymyxin B
      treatment failed to affect scratching behavior. These results suggest that oral
      administration of kanamycin during infancy promoted the development of atopic
      dermatitis-like skin lesions in NC/Nga mice and was associated with a transient
      change in intestinal microbiota.

PMID- 20139607
TI  - Structural and functional characterization of recombinant human serum transferrin
      secreted from Pichia pastoris.
AB  - Serum transferrin is an iron-binding glycoprotein with a bilobal structure. It
      binds iron ions in the blood serum and delivers them into target cells via
      transferrin receptor. We identified structural and functional characteristics of
      recombinant human transferrin which is produced in the yeast Pichia pastoris.
      Using the signal sequence of the alpha factor of the yeast Saccharomyces
      cerevisiae, high-level secretion was obtained, up to 30 mg/l of culture medium.
      Correct processing at designed sites was confirmed by N-terminal sequence
      analysis. Carbohydrate modification was determined by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis
      after digestion with endo-beta-N-acetylglucosaminidase H. Reflecting the
      secondary structure, the circular dichroism spectrum of the recombinant protein
      was indistinguishable from that of serum transferrin. Consequently, the
      recombinant product had an iron binding function just as the serum specimen has:
      two Fe(3+) sites existed in a recombinant transferrin molecule, as estimated by
      titration analysis using visible absorption, fluorescence spectra, and
      electrophoretic behavior in urea denaturing polyacrylamide gel electrophoresis
      (PAGE).

PMID- 20139608
TI  - Synthesis of anti-tumor dimeric indole alkaloids in catharanthus roseus was
      promoted by irradiation with near-ultraviolet light at low temperature.
AB  - We have found that coupling between catharanthine and vindoline occurs non
      enzymatically in the presence of flavin mononucleotide and manganese ions with
      near-ultraviolet light irradiation in vitro. The present study found that the
      concentrations of catharanthine and vindoline in Catharanthus roseus decreased
      and those of dimeric indole alkaloids increased under near-ultraviolet light at 4
      degrees C. It indicates that this coupling reaction at 4 degrees C occurs non
      enzymatically.

PMID- 20139609
TI  - Inulin-type fructans stimulated the growth of exogenously administered
      Lactobacillus plantarum No. 14 in the mouse gastrointestinal tract.
AB  - This study examined the effects of the inulin-type fructans known as fructo
      oligosaccharide (FOS) and inulin on the growth and persistence of Lactobacillus
      plantarum No. 14 (LP14) in the gut. Cultivation in medium that contained either
      FOS or inulin revealed that both fructans supported the growth of LP14. Fecal
      recovery of viable L. plantarum at 24 and 30 h following administration of LP14
      were highest in mice fed inulin, followed by mice fed FOS and the control diet.
      However, neither of the fructans prolonged the appearance of LP14 in the gut.
      Cultivation in fecal extract medium prepared from mice fed each of the test diets
      showed higher growth of LP14 in the mice fed fructans. Histological analysis
      following fluorescein-stained LP14 administration showed that LP14 was largely
      localized to the luminal contents. These results suggest that inulin-type
      fructans support the growth of LP14 in the luminal contents only during their
      passage through the gut.

PMID- 20139610
TI  - Prorenin processing enzyme (PPE) produced by Baculovirus-infected Sf-9 insect
      cells: PPE is the cysteine protease encoded in the acMNPV gene.
AB  - In infection cultures of Spodoptera frugiperda (Sf-9) insect cells with a
      recombinant baculovirus, vhpR, carrying human preprorenin cDNA in the polyhedrin
      locus of Autographa californica multiple nuclear polyhedrosis virus (AcMNPV), the
      expressed inactive recombinant human (rh)-prorenin is reported to be
      proteolytically processed to yield active rh-renin in the very late phase of
      culture (Takahashi et al., Biosci. Biotechnol. Biochem., 71, 2610-2613 (2007)).
      To identify the enzyme that catalyzes the processing of rh-prorenin, referred to
      as prorenin processing enzyme (PPE), we purified potential PPE from virus
      infected Sf-9 culture supernatant by the use of an internally quenched
      fluorescent (IQF) substrate for PPE. The 32-kDa protein band agreed well with PPE
      activity on the final Mono Q FPLC. By N-terminal amino acid sequence analysis,
      the protein was revealed to be a cysteine protease encoded by the AcMNPV gene.
      Enzyme activity was inhibited by cysteine protease inhibitors but not by other
      protease inhibitors. When the purified rh-prorenin was incubated with the 32-kDa
      protein, renin activity appeared concomitant with the disappearance of rh
      prorenin. The N-terminal amino acid sequence of the activated product was
      identical to that of the rh-renin that had accumulated in the infection cultures.
      These results indicate that the 32-kDa cysteine protease derived from the AcMNPV
      gene is the enzyme PPE of virus-infected Sf-9 cells.

PMID- 20139611
TI  - L-Trp and L-Leu-OEt derivatives of the monascus pigment exert high anti-obesity
      effects on mice.
AB  - High-fat diets (HFDs) supplemented with the L-Trp and L-Leu-OEt derivatives of
      the monascus pigment were fed to mice. Compared to the HFD group, the average
      body weight gain of the four HFD-pigment groups was decreased by 13.6-50.9%, and
      the intra-peritoneal adipose tissues weight was reduced by 16.7-30.5%. The
      derivatives also reduced the respective serum total cholesterol and triglyceride
      levels of the mice by 9.7-14.4% and 12.5-17.2%. The L-Trp derivative greatly
      increased the HDL-cholesterol level by 64.8-66.4% and the HTR value by 73.8
      81.7%. The L-Leu-OEt and L-Trp derivatives decreased the total cholesterol level
      in the mice liver by 9.7-24.2% and 36.2-39.9%, respectively. Reductions in the
      triglyceride level were 21.5-22.4% for the L-Leu-OEt derivative and 17.9-18.8%
      for the L-Trp derivative. The L-Leu-OEt derivative exhibited higher in vitro
      inhibitory activities against HMG-CoA reductase and lipoprotein lipase than the L
      Trp derivative. An in vivo test with mice showed the L-Trp derivative to have
      higher anti-obesity effects than the L-Leu-OEt derivative.

PMID- 20139612
TI  - Behavior of various hosts of the IncP-7 carbazole-degradative plasmid pCAR1 in
      artificial microcosms.
AB  - pCAR1 endows carbazole-degrading ability on its host. Three different host
      Pseudomonas (P. fluorescens Pf0-1, P. resinovorans CA10dm4, and P. chlororaphis
      IAM1511) were prepared to compare their behaviors in artificial microcosms
      (sterile soil and water supplemented with carbazole) with previous results for P.
      putida SM1443 (Shintani et al., Appl. Microbiol. Biotechnol., 80, 485-497
      (2008)). We monitored carbazole degradation, bacterial survival, and conjugative
      transfer of pCAR1. Carbazole degradations were not detected with any of three
      hosts in the soil microcosms, but were in most of the water microcosms.
      Degradative efficiency varied host by host. SM1443 is an appropriate host for
      carbazole degradation in soil microcosms, while CA10dm4 is for water microcosms.
      pCAR1 transfers were detected only in the water microcosms inoculated with SM1443
      or IAM1511 as the host. This is the first report to compare the behaviors of
      various hosts of the same plasmid in these microcosms.

PMID- 20139613
TI  - An active part of Artemisia sacrorum Ledeb. attenuates hepatic lipid accumulation
      through activating AMP-activated protein kinase in human HepG2 cells.
AB  - Artemisia sacrorum Ledeb. (Compositae) (ASL) is a traditional Chinese medicine
      used to treat different hepatic diseases. However, a hypolipidemic effect of ASL
      on fatty liver disease has not been reported. Therefore, we investigated whether
      95% ethanol eluate (EE), an active part of ASL, would attenuate hepatic lipid
      accumulation in human HepG2 cells by activating AMP-activated protein kinase
      (AMPK). Significant decreases in triglyceride levels and increases in AMPK and
      acetyl-CoA carboxylase (ACC) phosphorylation were observed when the cells were
      treated with 95% EE. EE down-regulated the lipogenesis gene expression of sterol
      regulatory element-binding protein 1c (SREBP1c) and its target genes, such as
      fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), in a time- and
      dose-dependent manner. In contrast, the lipolytic gene expression of peroxisome
      proliferator-activated receptor alpha (PPAR-alpha) and CD36 increased in a time-
      and dose-dependent manner. These effects were abolished by pretreatment with
      compound C, an AMPK inhibitor. However, there were no differences in the gene
      expression of SREBP2, low density lipoprotein receptor (LDLR), hydroxymethyl
      glutaryl CoA reductase (HMG-CoA), or glucose transporter 2 (GLUT2). At the same
      time, 95% EE significantly increased the gene expression of acyl CoA oxidase
      (ACOX) in a time- and dose-dependent manner. Thus, AMPK mediated 95% EE induced
      suppression of SREBP1c and activation of PPAR-alpha respectively. These finding
      indicate that 95% EE attenuates hepatic lipid accumulation through AMPK
      activation and may be active in the prevention of serious diseases such as fatty
      liver, obesity, and type-2 diabetic mellitus.

PMID- 20139614
TI  - Development of a fucoidan-specific antibody and measurement of fucoidan in serum
      and urine by sandwich ELISA.
AB  - Fucoidan exhibits various biological properties. We raised a novel antibody
      against fucoidan extracted from Cladosiphon okamuranus and developed a sandwich
      ELISA method to measure fucoidan. The fucoidan antibody was specific and did not
      cross-react with other polysulfated polysaccharides. Fucoidan recovery from serum
      and urine by ELISA was 86-113%. Intra- and inter-assay CVs were 1.5-13.4%. Assay
      linearity was maintained after 3-fold dilution of each sample with phosphate
      buffer saline (PBS). In the serum and urine of healthy volunteers (n=10),
      fucoidan was not detected before administration, and the levels markedly
      increased 6 and 9 h after oral administration. The molecular weight of the serum
      fucoidan determined by HPLC gel filtration remained unchanged, whereas that of
      urine fucoidan was significantly reduced. This is the first ELISA method of
      measuring serum and urine fucoidan levels after oral administration. The method
      is simple, reliable, and practical for the analysis of samples, especially urine
      samples.

PMID- 20139615
TI  - Welsh onion attenuates hyperlipidemia in rats fed on high-fat high-sucrose diet.
AB  - The effects of two types of Welsh onion, green-leafy and white-sheath types, on
      hyperlipidemia in rats fed on diets high in fat and sucrose were studied. A
      significant lowering effect on cholesterol in the plasma and on total lipids,
      triacylglycerol, and cholesterol in the liver was observed in rats fed on the
      green, but not white, Welsh onion. These Welsh onions had no significant effect
      on the hepatic enzyme activities responsible for fatty acid synthesis and
      degradation. The results suggest that the green Welsh onion might be effective in
      attenuating hyperlipidemia in a manner other than affecting fatty acid metabolism
      in the liver. Kaempferol seemed to be one of the components in green Welsh onion
      acting to lower lipid deposition.

PMID- 20139616
TI  - Antibiotic susceptibility of bifidobacterial strains distributed in the Japanese
      market.
AB  - The aim of the present study was to analyze the antibiotic susceptibility of
      bifidobacterial strains distributed in the Japanese market. A total of 23
      strains, including probiotic isolates from foods, supplements, pharmaceuticals
      and reference strains of each species (or subspecies), were tested for
      susceptibility to 15 antibiotics by the broth microdilution method and examined
      for the presence of possible resistant determinants. The strains were susceptible
      overall to chloramphenicol, ampicillin, vancomycin and linezolid, and were
      intrinsically resistant to aminoglycoside group agents. Susceptibility to
      erythromycin, clindamycin, rifampicin, tetracycline and trimethoprim varied among
      the strains. All strains of Bifidobacterium animalis subsp. lactis were resistant
      to tetracycline and appeared to harbor tet(W) genes. No risk factor for safety
      was found for bifidobacterial strains distributed in the Japanese market in
      respect of their antimicrobial resistance, although the presence of the tet(W)
      gene in some strains stresses the need for future evaluation.

PMID- 20139617
TI  - Determination of sialyl and neutral oligosaccharide levels in transition and
      mature milks of Samoan women, using anthranilic derivatization followed by
      reverse phase high performance liquid chromatography.
AB  - An improved analytical method using reverse-phase high performance liquid
      chromatography following anthranilic acid derivatization for the measurement of
      each oligosaccharide level in transition (5 to 10 d lactation) and mature (21 to
      155 d lactation) milks of sixteen Samoan women is described. The method was
      applied for the measurement of sialyl as well as neutral oligosaccharide levels.
      We found that disialyllacto-N-tetraose (DSLNT), sialylacto-N-tetraose c (LSTc),
      and 6'-sialyllactose (6'-SL) were the most abundant of the sialyl
      oligosaccharides. In the neutral oligosaccharide fraction, lacto-N-fucopentaose
      II and III combined (LNFP II+III) were the most dominant, followed by lacto-N
      tetraose (LNT) and 3-fucosyllactose (3-FL). 2'-Fucosyllactose (2'-FL) and lacto-N
      fucopentaose I (LNFP I) were absent in some and found at low levels in most of
      the Samoan women. Our study indicates that the milk oligosaccharide composition
      in Samoan women is similar to that of Japanese women with respect to sialyl but
      not to neutral oligosaccharides. The differences in neutral oligosaccharides
      might have a genetic origin.

PMID- 20139618
TI  - Isolation and identification of FR198248, a hydroxylated 1,3
      dihydroisobenzofuran, from Aspergillus flavipes as an inhibitor of peptide
      deformylase.
AB  - Two highly hydroxylated 1,3-dihydroisobenzofurans, FR198248 (1) and FR202306 (2),
      were isolated as peptide deformylase (PDF) inhibitors from Aspergillus flavipes.
      Compounds 1 and 2 inhibited Staphylococus aureus PDF with IC(50) values of 3.6
      and 2.5 microM, respectively, and also showed antibacterial activity with an MIC
      value of 25 microg/ml. In contrast, 6-O-methyl derivative 3 of compound 2 was
      inactive against both PDF and S. aureus.

PMID- 20139619
TI  - Development of a highly sensitive latex reagent directed against C-reactive
      protein (CRP) using epitope analysis with monoclonal antibodies.
AB  - C-Reactive protein (CRP) is an acute-phase protein that increases during systemic
      inflammation and is currently one of the most frequently studied inflammatory
      markers in epidemiology. We have determined CRP concentration using novel latex
      reagent with polyclonal antibody. In the present study, we determined the
      concentration of CRP using monoclonal antibodies, and evaluated the interaction
      of antigen-antibody reactive sites and latex agglutination to detect low CRP
      concentrations. We developed four novel monoclonal antibodies that we classified
      into two major groups, and that were used to prepare the latex reagents. The
      latex reagents prepared using a cocktail of monoclonal antibodies for different
      epitopes appeared highly sensitive. The lower limit of CRP detection, which was
      defined using the mean 3 SD method, was calculated to be 5 ng/ml for the latex
      reagents when oligoclonal antibodies were utilized. Furthermore, the latex
      reagents were found to react specifically with CRP in clinical samples.

PMID- 20139620
TI  - A novel amphipathic linear peptide with both insect toxicity and antimicrobial
      activity from the venom of the scorpion Isometrus maculatus.
AB  - Scorpion venoms are composed of a number of peptides, many of which show
      neurotoxicity. In addition to these neurotoxins, several antimicrobial peptides
      have also been isolated from the venoms. The scorpion Isometrus maculatus,
      belonging to the Buthidae family, is found in many tropical regions including
      Japan, but little attention has been paid to its biological activity and chemical
      composition. In this study, we isolated a novel insect toxin, Im-1, by bioassay
      guided fractionation of the venom of I. maculatus. Rapid and reversible paralysis
      was observed after injection of Im-1 into crickets. Im-1 consists of 56 amino
      acids, and is predicted to form an amphipathic alpha-helix. Since Im-1 shares
      sequence similarity to an antimicrobial peptide, parabutoporin, we evaluated its
      effects on several bacterial strains and found that it showed an antimicrobial
      activity profile similar to parabutoporin. This suggests that Im-1 and
      parabutoporin exert their antimicrobial effects through similar mechanisms.

PMID- 20139621
TI  - Expression of mutant RPA in human cancer cells causes telomere shortening.
AB  - Replication protein A (RPA) binds to single-stranded DNA generated during DNA
      replication and other processes. The roles of RPA in telomere maintenance have
      been demonstrated in yeasts, but not in telomerase-positive human cells. In this
      study, we found that expression of mutant RPA70 in human cells caused telomere
      shortening, suggesting that RPA is required for telomere-length regulation in
      human cancer cells.

PMID- 20139622
TI  - Pediococcus pentosaceus Sn26 inhibits IgE production and the occurrence of
      ovalbumin-induced allergic diarrhea in mice.
AB  - We investigated the anti-allergic effect of a new strain (Pediococcus pentosaceus
      Sn26, the Sn26 strain) among 59 strains isolated from Japanese fermented
      vegetable pickles, the Sunki pickle. The Sn26 strain increased Th1 type cytokine
      (IL-12 and IFN-gamma) production of Peyer's patch (PP) cells in BALB/c mice,
      improved the Th1/Th2 balance, and inhibited IgE production of splenocytes of
      ovalbumin (OVA)-induced allergic diarrheic mice. Next we demonstrated, by
      neutralizing IL-12 and IFN-gamma, that the Sn26 strain first induced IL-12, that
      IL-12 induced IFN-gamma, and that decreases in IL-4 and IgE production followed.
      Furthermore, oral administration of the Sn26 strain decreased serum OVA-specific
      IgE levels and ameliorated the appearance of diarrhea in OVA-induced allergic
      diarrheic mice. Based on these results, it was assumed that oral administration
      of the Sn26 strain ameliorated type-1 allergies through improvement of the
      Th1/Th2 balance and decreases in IgE production.

PMID- 20139623
TI  - The hypoglycemic effects of Camellia assamica var. kucha extract.
AB  - Kucha (Camellia assamica var. kucha) is an endemic tea that grows in cloudy and
      foggy highlands in southwest China. Its hypoglycemic effects were studied here.
      The postprandial blood glucose levels in mice after sucrose and soluble starch
      loading were significantly reduced by Kucha administration. The glycosidase
      inhibitory activities were effective both in vitro and in vivo. It is concluded
      that the hypoglycemic effects of Kucha might be due to inhibition of
      disaccharidases activities.

PMID- 20139624
TI  - Structural changes in ribonuclease P RNA in the hyperthermophilic archaeon
      Pyrococcus horikoshii OT3 induced on interaction with proteins.
AB  - The activated structure of RNase P RNA (PhopRNA) in Pyrococcus horikoshii OT3 was
      characterized by circular dichroism (CD) and ultraviolet (UV) absorbance spectra.
      The results suggested that interaction of four RNase P proteins (PhoPop5,
      PhoRpp21, PhoRpp29, and PhoRpp30) with PhopRNA results in destabilization of base
      stacking in PhopRNA, whereas the addition of a fifth protein, PhoRpp38, increases
      base stacking in PhopRNA.

PMID- 20139625
TI  - Interaction between food substances and the intestinal epithelium.
AB  - The small intestine is an organ responsible for nutrient absorption, barrier
      functions, signal recognition/transduction, and the production of bioactive
      compounds. These functions are known to be regulated by such factors as hormones
      and cytokines, but substances contained in the daily diet are also thought to
      play roles as major modulators of intestinal functions. Intestinal epithelial
      cells (IECs), which form a monolayer covering the inside surface of the
      intestinal tract, are particularly important in this modulation, because they
      directly interact with intestinal contents, including food substances, their
      digests, and gut microbial components. Using cell-based in vitro assays, we
      investigated the food-IEC interactions at the cellular and molecular levels, and
      found that a variety of food substances affected the transporter activity, tight
      junction permeability, metabolic enzyme expression, immune functions, and so on.
      Modulation of the intestinal functions by dietary substances is therefore
      essential to promote health.

PMID- 20139626
TI  - Leonurus sibiricus herb extract suppresses oxidative stress and ameliorates
      hypercholesterolemia in C57BL/6 mice and TNF-alpha induced expression of adhesion
      molecules and lectin-like oxidized LDL receptor-1 in human umbilical vein
      endothelial cells.
AB  - In Leonurus sibiricus herb extract (LHE)-supplemented animals, plasma cholesterol
      decreased and high-density lipoprotein-cholesterol increased, resulting in a
      lowered atherogenic index. The plasma trolox equivalent antioxidant capacity,
      levels of hepatic thiobarbituric acid-reactive substances, and protein carbonyl
      values decreased significantly in LHE-supplemented mice (p<0.05), whereas the
      hepatic antioxidant indicators were all significantly elevated (p<0.05). In human
      umbilical vein endothelial cells stimulated with tumor necrosis factor alpha, LHE
      significantly suppressed intracellular reactive oxygen species, LOX-1, and
      adhesion molecules. LHE supplementation may modulate the lipoprotein composition
      and attenuate oxidative stress by elevated antioxidant processes, thus
      suppressing the activation of inflammatory mediators. This is a possible
      mechanism of the anti-atherogenic effect.

PMID- 20139627
TI  - Molecular mechanisms underlying sex pheromone production in moths.
AB  - Many species of female moths produce sex pheromones to attract conspecific males.
      Most moth species utilize Type I pheromones that consist of straight-chain
      compounds 10-18 carbons in length with a functional group of a primary alcohol,
      aldehyde, or acetate ester, and usually with several double bonds. Studies over
      the past three decades have demonstrated that female moths usually produce sex
      pheromones as multi-component blends in which the ratio of the individual
      components is precisely controlled, making it possible to generate species
      specific pheromone blends. As for the biosynthesis of Type I pheromones, it is
      well established that they are de novo synthesized in the pheromone gland (PG)
      through modifications of fatty acid biosynthetic pathways. However, because many
      of the molecular components within the PG cells (enzymes, proteins, and small
      regulatory molecules) had not been functionally characterized, the molecular
      mechanisms underlying sex pheromone production in PG cells remained poorly
      understood. To address this, we have characterized some of the key molecules
      involved in the biosynthesis of the sex pheromone bombykol in the silkmoth,
      Bombyx mori. Characterization of these molecules has facilitated our
      understanding of the precise mechanisms underlying lepidopteran sex pheromone
      production.

PMID- 20139628
TI  - Anti-inflammatory effects of gomisin N, gomisin J, and schisandrin C isolated
      from the fruit of Schisandra chinensis.
AB  - Schiandra chinensis is a well-known Chinese traditional medicine for the
      treatment of hepatic disease. In this study, we investigated whether the nine
      major compounds of Schiandra chinensis could be applied to suppress
      lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages
      (Raw 264.7 cells). Among the nine lignans, three, gomisin J, gomisin N, and
      schisandrin C, were found to reduce nitric oxide (NO) production from LPS
      stimulated Raw 264.7 cells. These three lignans showed low cytotoxic effects in
      Raw 264.7 cells. Pre-treatment of Raw 264.7 cells with gomisin J, gomisin N, or
      schisandrin C reduced the expression of mRNA and the secretion of pro
      inflammatory cytokines. These inhibitory effects were found to be caused by
      blockage of p38 mitogen-activated protein kinase (MAPK), extracellular signal
      regulated kinases 1 and 2 (ERK 1/2), and c-Jun N-terminal kinase (JNK)
      phosphorylation.

PMID- 20139629
TI  - Archaeal homologs of human RNase P protein pairs Pop5 with Rpp30 and Rpp21 with
      Rpp29 work on distinct functional domains of the RNA subunit.
AB  - We examined the functional equivalency between Escherichia coli RNase P protein
      (C5) and Pyrococcus horikoshii RNase P proteins (PhoPop5, PhoRpp21, PhoRpp29,
      PhoRpp30, and PhoRpp38) for RNase P activity. The C5 protein and P. horikoshii
      RNase P proteins were unable to activate non-congnate RNase P RNAs, P. horikoshii
      RNase P RNA (PhopRNA) and E. coli RNase P RNA (M1 RNA) respectively. Two chimeric
      RNAs, in which functional C- and S-domains of M1 RNA and PhopRNA were exchanged,
      were prepared and characterized with respect to the cleavage of P. horikoshii pre
      tRNA(Tyr) in the presence of C5 or P. horikoshii proteins. The results suggest
      that PhoPop5 and PhoRpp30 function equivalently to the C5 protein in the E. coli
      RNase P, being involved in activation of the PhopRNA C-domain. On the other hand,
      PhoRpp21 and PhoRpp29 are implicated in stabilization of the PhopRNA S-domain.

PMID- 20139630
TI  - Suppressive ability of defatted rice bran against lipid oxidation in cookies
      containing iron.
AB  - Cookies containing iron, defatted rice bran, and several oils were prepared, and
      their oxidative stability evaluated. Oxidation was suppressed by the defatted
      rice bran, but a limit to the suppressive effect was observed. The maximum
      peroxide values obtained with defatted rice bran were low, and similar,
      regardless of the degree of unsaturation of the oils. A chemical analysis
      suggested that proteins and polyphenols in the defatted rice bran contributed to
      the suppressive effect. Cookies without the defatted rice bran showed decreasing
      maximum peroxide value as the relative humidity increased. No such dependence was
      observed for the cookies containing defatted rice bran. The water sorption
      isotherm of defatted rice bran indicated that the weak dependence was due to low
      water sorption.

PMID- 20139631
TI  - Electrophiles in foods: the current status of isothiocyanates and their chemical
      biology.
AB  - Unlike many classical signals and hormones, exposure of the cells to
      electrophilic molecules potentially induces a series of characteristic and wide
      ranging biological responses by covalently attaching with macromolecules such as
      proteins as well as small cellular reductants. In addition to chemicals
      originated from xenobiotics or lipid peroxidation, electrophiles in foods have
      recently attracted much attention. These compounds have recently been found to
      induce expression of cytoprotective proteins that are involved in the elimination
      or inactivation of oxidative stress and carcinogenic electrophiles implicated in
      several pathogeneses. The redox-sensitive regulating systems such as
      Keap1/Nrf2/ARE play a key role in this induction and thus are considered to be
      the most important target of electrophiles in foods. This review highlights the
      food-derived electrophiles as promising protectors against various diseases, with
      an emphasis on possible molecular mechanisms. Current knowledge of
      isothiocyanates (ITCs), representative electrophile compounds from cruciferous
      vegetables, is discussed also, with consideration of the chemistry, metabolism,
      absorption, and factors influencing the biological activities of ITCs. In
      addition, this review attempts to provide a balanced perspective on the relative
      beneficial and harmful effects of the food electrophiles.

PMID- 20139632
TI  - Assessment of the biological similarity of three capsaicin analogs (Capsinoids)
      found in non-pungent chili pepper (CH-19 Sweet) fruits.
AB  - CH-19 Sweet is a newly found chili pepper breed bearing much less pungent fruits.
      Because CH-19 Sweet fruits were found to contain three analogs (capsinoids) of
      capsaicin, a major component of pungency of hot peppers (the analogs are capsiate
      or CST, dihydrocapsiate or DCT, and nordihydrocapsiate or NDCT), we assessed in
      this study the bio-potencies of these three capsinoids by comparing them with
      capsaicin. The three capsinoids bound to transient potential vanilloid 1 (TRPV1)
      receptors expressed in cultured cells and activated Ca(2+) influx in a
      concentration-dependent manner with similar magnitudes. In contrast to capsaicin,
      capsinoids at the same concentration induced virtually no nociceptive responses
      when applied to the eyes or the oral cavities of mice. Intravenous administration
      of capsaicin or 20-fold increased doses of each capsinoid to rats induced
      significant increases in plasma catecholamine levels. Orally administered, each
      capsinoid enhanced oxygen consumption in mice. Based on the present results,
      capsaicin and these three capsinoids should have similar bio-potency, though
      capsinoids do not generate pungency or sensory irritation.

PMID- 20139633
TI  - Short-term intermittent PTH 1-34 administration enhances bone formation in
      SCID/Beige mice.
AB  - The anabolic effect of intermittent PTH on bone is variable depending on the
      species studied, duration/mode of administration, and location of skeletal
      response investigated. We tested the hypothesis low dose, short term,
      intermittent PTH 1-34 administration is sufficient to enhance bone formation
      without altering bone resorption. To test our hypothesis, mice were treated
      intermittently with one of three concentrations of PTH 1-34 (1 microg/kg; low, 10
      microg/kg, or 20 microg/kg; high) for three weeks. The skeletal response was
      identified by quantifying: serum markers of bone turnover, cancellous bone
      parameters in distal femur, proximal tibia, and lumbar vertebrae by microCT, and
      number of osteoblasts and osteoclasts in distal femur. Mice receiving 20
      microg/kg of PTH 1-34 demonstrated a 30% increase in serum osteocalcin, but no
      differences in serum calcium, type I collagen teleopeptides, or TRACP 5b. For all
      bones, microCT analysis suggested mice receiving 20 microg/kg of PTH 1-34 had
      increased cancellous bone mineral density, trabecular thickness and spacing, but
      decreased trabecular number. A 60% increase in the number of alkaline phosphatase
      positive osteoblasts in the distal femur was also observed in tissue sections;
      however, the number of TRAP positive osteoclasts was not different between test
      and control groups. While animals administered 10 microg/kg demonstrated similar
      trends for all bone turnover indices, such alterations were not observed in
      animals administered PTH 1-34 at 1 microg/kg per day. Thus, PTH 1-34,
      administered intermittently for three weeks at 20 microg/kg is sufficient to
      enhance bone formation without enhancing resorption.

PMID- 20139634
TI  - Evaluation of plasma, salivary, and urinary cortisol levels for diagnosis of
      Cushing's syndrome.
AB  - As a screening test for Cushing's syndrome, the evaluation of late-night cortisol
      levels is indispensable. We evaluated the usefulness and accuracy of plasma,
      urinary, and salivary cortisol levels measured late at night for the diagnosis of
      Cushing's syndrome. High cortisol levels (> 5 microg/dL) during the night are
      indicative of Cushing's syndrome, although night plasma cortisol levels are not
      readily reproducible because of the stressful situation. There was no correlation
      between plasma and urinary cortisol levels late at night, and late-night urinary
      cortisol levels provided weak information for the diagnosis of Cushing's
      syndrome. By contrast, late-night plasma and salivary cortisol levels showed a
      positive correlation, and salivary cortisol sampling was found to be useful for
      the diagnosis of Cushing's syndrome, because more than 0.4 microg/dL of late
      night salivary cortisol levels gave a sensitivity of 86% and a specificity of
      100% in our hospital. This method is also useful for the diagnosis of early or
      mild stage Cushing's syndrome, so-called subclinical Cushing's syndrome. Inherent
      differences between assays make it difficult to define optimal diagnostic
      criteria. However, the relative levels of salivary cortisol ratio, which is
      presented as a relative level, compared with the mean levels of healthy subjects
      in each institute, is useful for the screening of Cushing's syndrome as the cut
      off level of 1.5 shows both high sensitivity and specificity in subclinical and
      overt Cushing's syndrome. Late-night salivary cortisol measurement is therefore a
      primary method of choice in the screening of patients suspected of having
      Cushing's syndrome.

PMID- 20139636
TI  - [Development of "Field Medicine" for the elderly from Kahoku in Japan to Asian
      worlds].

PMID- 20139635
TI  - Hormonal regulation of acetyl-CoA carboxylase isoenzyme gene transcription.
AB  - Both glucocorticoid and insulin are known to have an anabolic effect on
      lipogenesis. Acetyl-CoA, an intermediate product of glycolysis, is supplied for
      fatty acid synthesis when carbohydrate intake is sufficient. Acetyl-CoA
      carboxylase (ACC), consisting of two isoenzymes ACC1 and ACC2, mediates the
      conversion from acetyl-CoA to malonyl-CoA, and thus plays a key role for the
      regulation of lipogenesis. In this study, we surveyed the effects of
      glucocorticoid and insulin on the transcriptional activity of the alternative
      promoters of ACCs (PI-PIII for ACC1, and PI and PII for ACC2) using the HepG2
      human hepatocyte cell line in vitro. We also examined the roles of the insulin
      and/or glucose-regulated transcriptional factor(s) such as SREBP1c,
      LXRalpha/beta, and ChREBP on each promoter of the ACC genes. We found that both
      insulin and glucocorticoid had potent positive effects on all the promoters
      examined, and additive effects of both hormones were recognized in ACC1 PI and
      ACC2 PI. Furthermore, a representative insulin-responsive transcription factor
      SREBP1c showed significant stimulatory effects on all the promoters of ACC genes,
      among which those on ACC1 PIII and ACC2 PI were most prominent. On the other
      hand, the effect of LXRalpha was rather selective; it showed a marked stimulatory
      effect only on ACC1 PII. LXRbeta and ChREBP had minimal, if any, effects on some
      of the promoters. Altogether, our data suggest that insulin and glucocorticoid
      have positive effects on both ACC1 and ACC2 gene transcription. SREBP1c might be
      a master regulator of the expression of both genes regardless of the promoter
      utilized, whereas LXRalpha seems to play a promoter-specific role. Since ACC1
      facilitates lipogenesis by stimulating fatty acid synthesis and ACC2 inhibits
      lipolysis, both insulin and glucocorticoid seem to play an important role in the
      pathogenesis of obesity and/or hepatic steatosis.

PMID- 20139637
TI  - [Hypertension research originating from Okohcho].

PMID- 20139638
TI  - [Seven-day (24-hour) ambulatory blood pressure monitoring and frequently observed
      day-to-day differences in the elderly].
AB  - AIM: The goal of this study was to quantify the extent of possible day-to-day
      differences in 24-hour ambulatory blood pressure (ABP) monitoring results
      especially in association with age. METHOD: A total of 514 community-dwelling
      subjects were initially recruited to participate in this study, and 450 subjects
      (average 58.8 years, 186 men and 264 women) had ABP monitoring for at least 6
      days using an oscillometric monitor (TM-2430). We calculated the mean ABP and
      blood pressure (BP) dipping ratio for each day. Subjects were divided into 3
      groups, 91 subjects aged from 40 to 49 years (average 41.8 years, younger group),
      192 subjects from 50 to 64 years (average 57.5 years, middle-aged group), and 167
      subjects over 65 years of age (average 69.5 years, elderly group). A mean ABP of
      >130/80 mm Hg was a criteria for hypertension (HT), and a decrease of less than
      10% in BP during the night was defined as non-dipper. From the view point of day
      to-day difference of ABP, 450 subjects were classified into (1) persistent
      normotension, masked ABP HT, intermittent ABP HT and persistent HT, and (2)
      persistent dipper, masked non-dipper, intermittent non-dipper and persistent non
      dipper. RESULTS: Frequency of masked and intermittent ABP HT was higher in the
      elderly group than the younger or middle-aged groups (47.3% vs. 27.5% or 39.6%),
      and the frequency of masked and intermittent non-dippers was also higher in
      association with age (55.0%, 59.5%, 69.7%, p<0.01). CONCLUSION: Aging can affect
      ABP variability. ABP monitoring should be used more precisely for the better
      diagnosis and treatment of HT in the elderly.

PMID- 20139639
TI  - [Regional network for the treatment of acute myocardial infarction].

PMID- 20139640
TI  - [A hint of the community medicine reproduction to be able to see from medical
      care in remote areas and remote islands].

PMID- 20139641
TI  - [The prescription to save the collapse of Japan medical system].

PMID- 20139642
TI  - [How to make regional medicine revive from the medical crisis or collapse due to
      the severe paucity of medical doctors: a plan with "the magnet hospital"].
AB  - BACKGROUND: In 2002-2003, the practice of doctors lending their names to appear
      as "staff" of hospitals became known. Problems regarding funds from public
      hospitals were also revealed. Tohoku University asked regional societies how to
      improve the medical situation, and redefined its responsibilities. The
      Educational Development Center for Local Medicine and Department of Local Medical
      Service System were set up (2005-2008). INVESTIGATION AND RESEARCH: A severe
      shortage of medical doctors prevails in Japan: the number of doctors per
      population is at the 4th lowest among OECD countries, and the number per hospital
      bed is the lowest. We have no nursing homes whose beds are not counted as
      hospital beds. The number of faculty staff in Japanese medical schools is 1/3 to
      those of Western countries. The reported number of doctors working in hospitals
      and offices surpasses that by census for medical doctors by >40,000. Japanese
      doctors work for >60 hours per week. RESULTS AND CONCLUSIONS: I propose essential
      plans to improve Japanese situation for medical service: 1. Immediately increase
      the number of doctors by at least 50%. Based on our calculation, we need 450,000
      doctors. 2. When the shortage of doctors is severe, establish a magnet hospital
      with c.a. 500 beds for every 200,000 population, capable of treating highly
      emergency patients and attracting doctors who need medical training. Hospitals
      should not belong to each city or town. 3. Establish a comprehensive organization
      to nurture doctors on a long-term basis. It should consist of a medical school,
      hospitals, and the prefectural government. It should help doctors to move between
      hospitals, and be responsible both for designing doctors' career paths and for
      allocating them appropriately.

PMID- 20139643
TI  - [Challenges for a regional university hospital].

PMID- 20139644
TI  - [Practical considerations on nutrition for the elderly at the end-of-life stage].

PMID- 20139645
TI  - [Nutrition methods of terminal elderly at the institution].

PMID- 20139646
TI  - [Nutritional issue of home care elderly in end of life].

PMID- 20139647
TI  - [Tube feeding in the bedridden elderly patients].

PMID- 20139648
TI  - [Cooperation in the nutritional care at the end-of-life].

PMID- 20139649
TI  - [Influence of plasma glucose variability and age on onset of diabetic retinopathy
      in diabetic patients analysis of results of long-term outpatient follow-up for 30
      years or more].
AB  - AIM: Diabetes mellitus (DM) outpatients were followed for 30 years or more. The
      impact of age and variability of fasting plasma glucose (FPG) and HbA(1C) on the
      onset of simple diabetic retinopathy (SDR) was analyzed. METHODS: The analysis
      included 84 DM patients who were free of retinopathy on their first visit between
      1969 and 1977, then followed at the outpatients clinic through 2006. The plasma
      glucose and HbA(1C) were measured on every visit. The indices of variability were
      expressed as standard deviation (SD), coefficient of variance (CV) and range.
      RESULTS: The SDR incidence was significantly higher in the group of FPG SD > or
      =37 mg/dl (n=21) than in that of < 37 mg/dl (n=63). The hazard ratio, adjusted
      for the mean FPG, presence of hypoglycemia, age, duration of diabetes,
      hypertension and treatment of diabetes was 2.64 (95% CI: 1.26-5.50). The mean
      HbA(1C), HbA(1C) SD, mean FPG and FPG SD were significant risk factors for onset
      of SDR. Multivariate analysis identified the mean HbA(1C) and FPG SD as
      significant independent factors of increase in the risk of SDR onset. The SDR
      incidence was significantly lower in those aged 42 y or more (n=45) than in those
      under 42 y (n=39). The hazard ratio, adjusted for the mean FPG, gender, duration
      of diabetes, hypertension, and treatment of diabetes was 0.53 (95% CI: 0.30
      0.95). All values for mean, SD and CV of FPG were significantly lower in the age
      group of > or = 42 y. CONCLUSIONS: The risk of SDR onset in DM patients increased
      with the mean values of HbA(1C) and/or FPG and also with the variability of these
      parameters. The risk decreased in the group above age 42, which was speculated to
      be due to the smaller variability in FPG and also due to the fact that subjects
      included in the group started SDR at the age exceeded the age of predilection for
      SDR onset.

PMID- 20139650
TI  - [Analysis of issues of insulin self-injection in elderly].
AB  - AIM AND METHOD: To elucidate the problems of insulin self-injection in elderly,
      we evaluated the procedure in 194 outpatients, using a checklist. RESULT: Errors
      in insulin self-injection were found in about two-thirds of patients. There is no
      difference in error frequency among any age group. Also, there was no error
      difference between the elderly group (people aged 65 or over) and the adult group
      (under 65). However, there were more errors in the elderly group than in the
      adult group on rechecking after guidance. CONCLUSION: It is necessary to perform
      periodical confirmation of insulin self-injection at all ages. In particular,
      early re-inspection should be done in the elderly patients.

PMID- 20139651
TI  - [Marked PT-INR prolongation associated with appetite loss due to urinary tract
      infection in a late elderly case with chronic atrial fibrillation].
AB  - An 80-year old woman presented with macroscopic hematuria on June 4(th), 2008.
      She had been suffering from general malaise and appetite loss since about 10 days
      previously. She had received anticoagulant therapy with warfarin due to chronic
      atrial fibrillation and PT-INR was well controlled between 1.6-2.2. When she
      presented, PT-INR was 12.88, and urinary tract infection (UTI) and
      hypoalbuminemia (2.2 g/dl) were observed. Therefore, warfarin therapy was
      discontinued, and antibiotics and vitamin K were administered. Normalization of
      PT-INR resulted in the disappearance of hematuria and UTI improved as a result of
      antibiotics administration. As the appetite loss improved, for serum albumin
      level increased. The previous dose of warfarin achieved PT-INR around 1.8. Her
      drug compliance had been good, and she took no drug nor food which could interact
      with warfarin. We also found no liver dysfunction, acute renal failure,
      malignancy, nor hyper- or hypo-thyroidism. Hypoalbuminemia caused by appetite
      loss due to UTI seems very likely to increase concentration of circulating free
      warfarin resulting in extreme prolongation of PT-INR. Our findings in the present
      case may suggest that we should pay more attention on changes of drug
      pharmacokinetics in elderly patients because of their poor adaptation to their
      circumstances such as infection or dehydration.

PMID- 20139652
TI  - [A case of type 2 diabetes mellitus associated with familial hypercholesterolemia
      confirming the improvement of blood glucose control by colestimide].
AB  - A 65-year-old woman had been treated for type 2 diabetes mellitus, familial
      hypercholesterolemia and old myocardial infarction. Combination therapy of
      atorvastatin (40 mg/day), ethyl icosapentate (1,200 mg/day), probucol (500
      mg/day) and colestimide (1 g/day) had never reached an ideal low-density
      lipoprotein cholesterol (LDL-C) level. However the conversion to high dose of
      colestimide (4 g/day) with the same dose of atorvastatin, ethyl icosapentate, and
      probucol obviously decreased her LDL-C level from 181.2 mg/dl to 148 mg/dl.
      Reduction of LDL-C level was also associated with the lowering of glycohemoglobin
      A1c from 10.7% to 8.7% simultaneously. Challenge tests by the cessation and
      resumption of only colestimide treatment clearly indicated that colestimide has
      both cholesterol and blood glucose lowering effect. Her body weight and appetite
      did not change by colestimide treatment. We think that colestimide therapy might
      provide a beneficial effect on atherosclerotic disease in diabetes mellitus with
      dyslipidemia through reduction of cholesterol and blood glucose.

PMID- 20139653
TI  - [A case of a primary effusion lymphoma in the elderly].
AB  - We report a 90-year-old man who was given a diagnosis of pleural effusion
      lymphoma (PEL) based on the detailed immunochemical and DNA analyses of the
      pleural effusion. He was bed-ridden and on enteral nutrition due to severe
      Alzheimer's disease, and also had diabetes mellitus. He was transferred to our
      hospital with fever and massive pleural effusion. A cytological examination of
      the pleural effusion revealed class 5 atypical lymphocytes with a high
      nucleus/cytoplasm ratio. The origin of the atypical cells could not be determined
      by flow cytometry of the pleural effusion, which only suggested the existence of
      inflammatory changes. Considering his general physical status, further
      investigations were not performed. The respiratory failure progressed, and he
      died on the 45(th) hospital day. At autopsy, no atypical cells were identified in
      his organs other than in the right thoracic space. We conducted immunochemical
      staining after making a cell block from the effusion sample. Most of the atypical
      cells were CD30 positive, with human herpes virus-8 (HHV-8)-associated protein. A
      PCR analysis of the immunoglobulin heavy chain gene detected monoclonal
      rearrangement, thus indicating the atypical cells to be involved in the B-cell
      lineage. These findings led to a final diagnosis of PEL. PEL is a rare type of
      lymphoma confined to the body cavities without any prominent tumor mass, and its
      pathogenesis is related to HHV-8 infection. PEL develops mostly in
      immunocompromised patients, such as those with AIDS. However, it may also occur
      in elderly patients as well. We should therefore also consider the possibility of
      PEL in elderly patients presenting with pleural effusion of unknown origin.

PMID- 20139654
TI  - [Frontotemporal dementia with motor neuron disease diagnosed after the
      development of type II respiratory failure].
AB  - A 79-year-old woman attended the Center for Comprehensive Care of Memory
      Disorders at the Kyorin University Hospital in 2006 due to forgetfulness. Her
      initial diagnosis was vascular dementia. In 2007, her cognition declined
      gradually. Then, impaired verbal fluency and stuttering, the symptoms of non
      fluent aphasia, were presented. Thereafter, 5 mg/day donepezil hydrochloride was
      prescribed. She later suffered type II respiratory failure. Needle
      electromyography revealed denervation of lower motor neurons. This led to the
      diagnosis of frontotemporal dementia with motor neuron disease. Interestingly,
      before developing type II respiratory failure, cognitive decline and non-fluent
      aphasia occurred in this case.

PMID- 20139655
TI  - [Visiting home care for old patients: comparative study of home- and hospital
      deaths].

PMID- 20139656
TI  - [Clinical process guideline for end-of-life care st geriatric health services
      facilities].

PMID- 20139657
TI  - Using functional data analysis models to estimate future time trends in age
      specific breast cancer mortality for the United States and England-Wales.
AB  - BACKGROUND: Mortality/incidence predictions are used for allocating public health
      resources and should accurately reflect age-related changes through time. We
      present a new forecasting model for estimating future trends in age-related
      breast cancer mortality for the United States and England-Wales. METHODS: We used
      functional data analysis techniques both to model breast cancer mortality-age
      relationships in the United States from 1950 through 2001 and England-Wales from
      1950 through 2003 and to estimate 20-year predictions using a new forecasting
      method. RESULTS: In the United States, trends for women aged 45 to 54 years have
      continued to decline since 1980. In contrast, trends in women aged 60 to 84 years
      increased in the 1980s and declined in the 1990s. For England-Wales, trends for
      women aged 45 to 74 years slightly increased before 1980, but declined
      thereafter. The greatest age-related changes for both regions were during the
      1990s. For both the United States and England-Wales, trends are expected to
      decline and then stabilize, with the greatest decline in women aged 60 to 70
      years. Forecasts suggest relatively stable trends for women older than 75 years.
      CONCLUSIONS: Prediction of age-related changes in mortality/incidence can be used
      for planning and targeting programs for specific age groups. Currently, these
      models are being extended to incorporate other variables that may influence age
      related changes in mortality/incidence trends. In their current form, these
      models will be most useful for modeling and projecting future trends of diseases
      for which there has been very little advancement in treatment and minimal cohort
      effects (eg. lethal cancers).

PMID- 20139658
TI  - Utility of subjective sleep assessment tools for healthy preschool children: a
      comparative study between sleep logs, questionnaires, and actigraphy.
AB  - BACKGROUND: Sleep pattern is an important factor in a child's mental, behavioural
      and physical status. To evaluate the sleep patterns of children, subjective tools
      such as sleep logs and questionnaires are still widely used in addition to
      objective methods of sleep assessment. Despite the established correlation
      between subjective and objective sleep variables, the characteristic features of
      subjective assessment have not been elucidated. METHODS: To investigate the
      characteristics of parental sleep assessment (daily sleep log and brief
      questionnaire) in preschool children, a 7-day actigraphic sleep study was
      conducted in 48 healthy 5-year-old children. RESULTS: Sleep schedule variables in
      the parental reports generally correlated well with actigraphic assessment of
      sleep patterns; however, sleep periods were longer in parental reports than in
      actigraphic recordings. Although the daily sleep log was better correlated with
      actigraphy, the brief questionnaire showed a good correlation with sleep pattern
      on weekday actigraphic assessments. Parental reports recorded fewer than 10% of
      the night wakings recorded by actigraphy. CONCLUSIONS: Subjective sleep
      assessments remain useful, although their utility depends on the purpose and size
      of the study in question. However, knowledge of the potential biases and
      characteristics of such assessments is essential for correct interpretation of
      the data.

PMID- 20139660
TI  - Immunization therapy for Alzheimer disease: a comprehensive review of active
      immunization strategies.
AB  - Based on the amyloid cascade hypothesis, various strategies targeting amyloid
      beta protein (Abeta) have been invented for prevention and treatment of Alzheimer
      disease (AD). Active and passive immunizations with Abeta and Abeta antibodies
      successfully reduced AD pathology and improved cognitive functions in an AD mouse
      model. However, active immunization with AN-1792, a mixture of Abeta1-42 peptide
      and adjuvant QS21 induced autoimmune encephalitis in humans. Surprisingly,
      although AN-1792 cleared senile plaque amyloid, it showed no benefit in humans.
      It is speculated that AN-1792 failed in deleting more toxic forms of Abeta such
      as oligomers and intracellular Abeta, suggesting that newly developing vaccines
      should delete these toxic molecules. Since T cell epitopes exist mainly in the C
      terminal portion of Abeta, vaccines using shorter N-terminal peptides are under
      development. In addition, since T helper 1 (Th1) immune responses activate
      encephalitogenic T cells and induce continuous inflammation in the central
      nervous system, vaccines inducing Th2 immune responses seem to be more promising.
      These are N-terminal short Abeta peptides with Th2 adjuvant or Th2-stimulating
      molecules, DNA vaccines, recombinant viral vector vaccines, recombinant
      vegetables and others. Improvement of vaccines will be also achieved by the
      administration method, because Th2 immune responses are mainly induced by mucosal
      or trans-cutaneous immunizations. Here I review recent progress in active
      immunization strategies for AD.

PMID- 20139659
TI  - The association between cancer risk and age at onset of smoking in Japanese.
AB  - BACKGROUND: Young age at onset of smoking is a known risk factor for cancer;
      however, few studies have investigated the risk of cancer associated with onset
      of smoking during adolescence in Japan. METHODS: We analyzed a portion of the
      data from a population-based cohort of 40 897 subjects aged 40 to 69 years with a
      history of smoking and no history of cancer at baseline. RESULTS: During a 14
      year follow-up period, 4386 total cancers and 681 lung cancers were newly
      diagnosed. As compared with smokers who started smoking after the age of 20
      years, those who started before the age of 17 years smoked a significantly larger
      number of cigarettes per day for a significantly longer duration; they also had a
      significantly higher risk of lung cancer. The hazard ratios in men and women were
      1.48 (95% confidence interval, 1.11-1.96) and 8.07 (2.34-27.85), respectively.
      After further adjustment for smoking amount, the associations remained
      significant. There was a statistically significant inverse correlation between
      lung cancer risk and age at onset of smoking in male current smokers whose
      baseline age was 50 to 59 years; no such association was detected among other age
      strata. CONCLUSIONS: There was no clear evidence of increased risk of cancer due
      to adolescent smoking. However, adolescent smoking appeared to indirectly
      increase lung cancer risk because it was associated with a longer duration and
      larger amount of smoking.

PMID- 20139661
TI  - Increase in the heart rate variability with deep breathing in diabetic patients
      after 12-month exercise training.
AB  - Autonomic neuropathy in diabetes leads to impaired regulation of blood pressure
      and heart rate variability (HRV), which is due to a shift in cardiac autonomic
      balance towards sympathetic dominance. Lower HRV has been considered a predictor
      of cardiac mortality and morbidity. Deep breathing test is a simple method to
      measure HRV and it provides a sensitive measure of cardiac autonomic function.
      The effect of long-term physical activity on HRV in type-2 diabetes mellitus is
      inconclusive. We aimed to evaluate the effects of regular physical exercise on
      HRV with deep breathing in type 2 diabetes (n = 105). Thirty normotensive
      diabetic patients and 25 hypertensive diabetic patients underwent physical
      exercise program for 12 months, and the other 50 patients (22 normotensive and 28
      hypertensive diabetic patients) were considered the non-exercised group.
      Electrocardiogram was recorded during deep breathing and HRV was measured.
      Regular exercise significantly increased HRV in diabetic patients with and
      without hypertension. The degree of the increase in HRV was greater in
      hypertensive diabetic patients (p < 0.01) than in normotensive diabetic patients
      (p < 0.05). After exercise, glycosylated hemoglobin levels were decreased in both
      groups of diabetic patients. Moreover, the hypertensive diabetic patients showed
      a decrease (p < 0.05) in blood pressure after regular exercise. Thus, regular
      exercise training increases HRV, suggesting that there is a shift in the cardiac
      sympathovagal balance in favor of parasympathetic dominance in diabetic patients.
      Long-term physical training may be an effective means to reverse the autonomic
      dysregulation seen in type 2 diabetes.

PMID- 20139662
TI  - High micronucleus frequency in peripheral blood lymphocytes of untreated cancer
      patients irrespective of gender, smoking and cancer sites.
AB  - Chromosomal instability could be one of primary causes for malignant cell
      transformation. The objective of the present study was to evaluate the
      spontaneous genetic damages in circulated lymphocytes of newly diagnosed cancer
      patients by using cytokinesis-block micronucleus (CBMN) assay, with respect to
      the factors that might affect micronucleus frequency (i.e. age, gender, smoking
      habits and cancer sites). Micronuclei (MN) are small nuclei that are originated
      from chromosome fragments or whole chromosomes. The analyzed samples included 44
      untreated cancer patients (19 females and 25 males with mean age of 60.89 years)
      with different cancer sites (12 patients with breast cancer, 5 with uterine
      cancer and 27 with cancer of pharynx). Control group included 40 healthy donors
      (28 females and 12 males with mean age of 43.95 years). The mean baseline MN
      frequency was significantly higher (p < 0.001) in cancer patients (15.18 +/- 5.05
      MN/1000 BN cells ranging from 4 to 27) than the baseline frequency in healthy
      controls (6.45 +/- 2.75 MN/1000 BN cells, ranging from 1 to 11). There was no
      gender difference in baseline MN frequency in cancer patients and healthy
      controls. Moreover, the MN frequency did not significantly differ among cancer
      sites, and between smokers and non-smokers in both patient and control samples.
      In conclusion, untreated cancer patients may be associated with an increase of
      chromosomal instability in peripheral blood lymphocytes, irrespective of gender,
      cigarette smoking and cancer sites.

PMID- 20139663
TI  - Gemtuzumab ozogamicin therapy for isolated extramedullary AML relapse after
      allogeneic hematopoietic stem-cell transplantation.
AB  - The treatment of isolated extramedullary relapse (IEMR) after allogeneic
      hematopoietic stem-cell transplantation (allo-HSCT) poses a challenge for which
      no standard approach exists. Gemtuzumab ozogamicin (GO) is a recombinant
      humanized monoclonal antibody, conjugated to calicheamicin, which targets the
      CD33 antigen that is expressed in acute myelogenous leukemia (AML) blasts. The
      selectivity of GO for CD33-positive leukemic cells makes it an attractive agent
      for use in patients with multiple sites of IEMR after allo-HSCT, because GO does
      not suppress cells responsible for the putative graft-versus-leukemia (GVL)
      effect. Herein, we describe a 54-year-old male patient who developed AML with
      multiple sites of extramedullary (EM) relapse after allo-HSCT, and who exhibited
      apparent donor-derived hematopoiesis in the bone marrow. At approximately 120
      days after allo-HSCT, the patient complained of severe lumbago. T2-weighted
      magnetic resonance images and fluorodeoxyglucose-positron emission tomography
      showed multiple mass lesions in soft tissue and bone. A biopsy specimen from a
      lumbar soft tissue mass confirmed EM relapse, and revealed that donor T
      lymphocytes were present in the relapse site and that leukemic cells expressed
      CD33. Therefore, to maintain the GVL effect of donor T lymphocytes, the patient
      was treated with GO as a single agent. He achieved complete hematological
      remission, and has remained in remission, with only mild liver injury, for more
      than 10 months since GO treatment. GO can be an effective therapy for IEMR after
      allo-HSCT, especially when cytotoxic T lymphocytes react to leukemic cells at the
      site of EM relapse.

PMID- 20139664
TI  - Fractionation of mature eosinophils in GATA-reporter transgenic mice.
AB  - Eosinophils contribute to the pathophysiology of allergic and infectious
      diseases, albeit their molecular functions remain unknown. Mature eosinophils are
      identified by their unique morphology and staining characteristics. However, it
      is difficult to fractionate living eosinophils by flow cytometry because these
      granulocytes express multiple cell surface markers that are shared by other cells
      of hematopoietic or non-hematopoietic origin. In this study, we describe a flow
      cytometry-based method to enumerate and fractionate eosinophils by developmental
      stages. To fractionate these cell types, we used transgenic mouse lines that
      express fluorescent proteins under control of the Gata1 gene hematopoietic
      regulatory region (Gata1-HRD), which is exclusively active in Gata1-expressing
      hematopoietic cells, including eosinophils. As expected, mature eosinophils were
      highly enriched in the fluorescent reporter-expressing subfraction of bone marrow
      myeloid cells that were negatively selected by using multiple antibodies against
      B220, CD4, CD8, Ter119, c-Kit and CD71. Cytochemical analyses of flow-sorted
      cells identified the cells in this fraction as eosinophils harboring eosinophilic
      granules. Additionally, expression of eosinophil-specific genes, for instance
      eosinophil enzymes and the IL-5 receptor alpha gene, were specifically detected
      in this fraction. The expression of these eosinophil-specific genes increased as
      the cells differentiated. This method for enrichment of bone marrow eosinophils
      is applicable to fractionation of eosinophils and bronchoalveolar lavage fluid
      from transgenic mice with atopic asthma. Thus, both pathological and
      developmental stages of eosinophils are efficiently fractionated by this flow
      cytometry-based method using Gata1-HRD transgenic reporter mice. This study,
      therefore, proposes a useful means to study the experimental allergic and
      inflammatory systems.

PMID- 20139665
TI  - Transplantation of mesenchymal stem cells preconditioned with diazoxide, a
      mitochondrial ATP-sensitive potassium channel opener, promotes repair of
      myocardial infarction in rats.
AB  - Myocardial infarction (MI) causes myocardium injury and scar formation, and the
      transmural infarction is associated with ventricular hypofunction. Stem cell
      transplantation therapy has improved cardiac function in animal models of MI.
      However, the poor survival of the donor cells in the host myocardium hampers the
      therapeutic efficacy of stem cell transplantation. Diazoxide, a mitochondrial ATP
      sensitive potassium channel opener, has been applied to suppress cell apoptosis
      and promote cell survival. We therefore assessed the effects of diazoxide on the
      selected mesenchymal stem cells (SMSCs). Pretreatment of SMSCs with diazoxide
      (200 micromol/L) for 30 min protected cells from oxidative stress injury by
      upregulating the expression of basic fibroblast growth factor and hepatocyte
      growth factor mRNAs and phospho-Akt and by preventing mitochondral cytochrome c
      translocation into the cytoplasm. Expression of mRNAs and proteins was detected
      by RT-PCR and western blot analyses. Thirty min after establishment of MI (the
      ligation of the left anterior descending of coronary artery) in female rats, the
      male rat SMSCs preconditioned with diazoxide were injected at four sites on the
      edge of the infarcted area. At 4 weeks after cell tranplantation, the donor cells
      in the recipient myocardium were tracked with Y chromosome. Preconditioning with
      diazoxide improved the survival rate of the transplanted SMSCs, compared to the
      untreated SMSCs. Moreover, transplantation of the diazoxide-pretreated SMSCs
      reduced the infarct size and increased left ventricular function, as judged by
      transthoracic echocardiography. In conclusion, diazoxide preconditioning is
      effective to promote SMSCs survival under oxidative stress and attenuates cardiac
      injury in MI.

PMID- 20139666
TI  - Long-term suicide mortality rates decrease in men and increase in women after the
      Niigata-Chuetsu earthquake in Japan.
AB  - A devastating earthquake causes psychological distress, and may increase suicide
      mortality thereafter, yet previous studies have made inconsistent conclusions
      regarding this issue. The purpose of the present study was to determine whether
      the 2004 Niigata-Chuetsu earthquake in Japan affected long-term mortality from
      suicide. We conducted a comparative study of suicide mortality rates during the 5
      year period preceding and the 3-year period following the earthquake in the
      disaster area and a control area in Niigata Prefecture, by analyzing death
      certificate data from October 1, 1999, to September 30, 2007. In men, baseline
      suicide mortality rates (5 years preceding the earthquake) were 48.4 per 100,000
      person-years in the disaster area and 46.1 in the control area, and suicide
      mortality rates during the 3-year period following the earthquake were 46.0 and
      45.1, respectively. In women, baseline suicide mortality rates were 22.3 in the
      disaster area and 18.7 in the control area, and post-earthquake suicide mortality
      rates were 20.2 and 15.3, respectively. In consequence, the decrease in suicide
      mortality rate during the 3 years post-earthquake was significantly higher in the
      disaster area (2.5) than in the control area (1.0) (p = 0.0013) in men, whereas
      the decrease in suicide mortality rate was 2.1 in the disaster area and 3.0 in
      the control area (p = 0.1246) in women. We have concluded that the long-term
      mortality from suicide after the earthquake decreases in men and increases in
      women, suggesting that post-earthquake suicide mortality is sex-dependent. Post
      earthquake suicide prevention strategies should more aggressively target women.

PMID- 20139667
TI  - Pretreatment with a traditional Chinese formula, guanxin II, reduces cardiac
      apoptosis via the Akt survival pathway in rats with myocardial ischemia.
AB  - Guanxin II (GXII) is a traditional Chinese formula to treat coronary heart
      disease in China. Previous studies indicate cardioprotection of GXII are related
      to cardiomyocyte apoptosis. Akt is necessary and sufficient for inhibition of
      apoptosis in cardiomyocytes. Our aim was to examine whether or not the
      antiapoptotic mechanisms of GXII are related to the Akt pathway. Male Sprague
      Dawley rats were randomly assigned to four groups: GXII administered at 2.5 or
      0.5 g raw materials/kg, the vehicle control and sham-operated oral 0.9% NaCl.
      They were pretreated once a day for 15 consecutive days by gavage. Thirty min
      after the last administration, the left anterior descending coronary artery was
      occluded to induce myocardial ischemia except for the sham-operated rats.
      Compared with rats receiving vehicle, those rats pretreated with GXII at 2.5 g/kg
      significantly reduced infarct size and decrease apoptosis. Furthermore, GXII (2.5
      g/kg) significantly activated Akt kinase, increased the Bcl-2/Bax ratio,
      inhibited cytochrome c release, reduced caspase-9 activation, and attenuated
      subsequent caspase-3 activation. GXII at 0.5 g/kg have no noticeable effect on
      these parameters. Meanwhile, GXII at 2.5 g/kg did not change myocardial blood
      flow of ischemic zone, indicating a direct action on cardiomyocytes. These
      results suggest GXII at 2.5 g/kg ensures the survival of myocardium by enhancing
      the Akt-mediated antiapoptosis pathway. The findings provide new evidence of the
      effective and safe therapy with GXII for patients with chronic coronary heart
      disease.

PMID- 20139669
TI  - Spectrophotometric evaluation of the age of bruises in children: measuring
      changes in bruise color as an indicator of child physical abuse.
AB  - Physical abuse of children is a severe social problem and is usually identified
      by the presence of bruises of various ages. The visual appearance of bruises is
      widely used to identify victims of abuse. Therefore, to objectively evaluate the
      age of bruises, we used a spectrophotometer to examine 86 bruises that occurred
      accidentally in healthy child volunteers, with consent from appropriate
      guardians. The bruise color was measured using a spectrophotometer and plotted
      using the CIE-L*a*b* color system, a method that expresses color numerically. The
      differences [Delta] in L* (lightness), a* (red and green content) and b* (yellow
      and blue content) color values relative to neighboring healthy/unbruised skin
      were measured for 7-10 days until the bruise disappeared. A characteristic
      pattern was observed in 21 bruises; DeltaL* increased from the negative peak and
      returned to baseline, Deltaa* decreased from the positive peak to baseline, and
      Deltab* increased above baseline and then slowly returned to baseline. The
      pattern of these color changes could be classified into three phases according to
      the time between bruising and the peak values for DeltaL* (negative peak, 38.9 +/
      19.5 hours), Deltaa* (positive peak, 37.6 +/- 21.7 hours), and Deltab* (negative
      and positive peak, 43.5 +/- 18.7 and 132.6 +/- 40.4 hours). Thus,
      spectrophotometric measurement of the color of bruises is helpful to estimate the
      approximate age of bruises and to distinguish between old and new bruises. This
      objective method could be introduced to clinical practice and social care to
      evaluate possible cases of child abuse.

PMID- 20139668
TI  - Genetic diagnosis of community-acquired MRSA: a multiplex real-time PCR method
      for Staphylococcal cassette chromosome mec typing and detecting toxin genes.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide range of
      infections in health care settings and community environments. In particular,
      community-acquired MRSA (CA-MRSA) is important for clinicians because many fatal
      cases in healthy populations have been reported. Staphylococcal cassette
      chromosome mec (SCCmec) is a mobile genetic element and carries the central
      determinant for broad-spectrum beta-lactam resistance encoded by the mecA gene.
      The emergence of MRSA is due to the acquisition and insertion of the SCCmec
      element into the chromosome. CA-MRSA is characterized as SCCmec type IV. Thus, we
      aimed to establish a novel multiplex real-time PCR method to distinguish SCCmec
      type, which enables us to evaluate the pathogenicity of MRSA. A total of 778 MRSA
      were isolated at Nagasaki University Hospital from 2000 to 2007. All isolates
      were subjected to minimal inhibitory concentration testing and PCR for SCCmec
      typing and detecting genes of toxins: tst (toxic shock syndrome toxin 1), sec
      (encoded enterotoxin type c), etb (exfoliative toxin type b), and lukS/F-PV
      (Panton-Valentine leukocidin). PCR was performed to amplify a total of 10 genes
      in the same run. The 667 MRSA clones detected from pus in 778 clones were
      classified as SCCmec type II (77.7%), type IV (19.2%), and type I (3.0%). 87.5%
      of SCCmec type II clone had tst and sec genes. No isolate was lukS/F-PV positive.
      The present study indicates the high rate of lukS/F-PV-negative SCCmec type IV in
      Nagasaki. Our PCR method is convenient for typing MRSA and detecting toxins in
      Japan.

PMID- 20139670
TI  - Growth and later health: a general perspective.
AB  - Whilst growth and its derangement in disease have been a long-standing focus in
      pediatrics, increasing evidence points to a further, fundamental role of early
      growth in the programming of later health. In studies on animals and humans,
      rapid early growth is associated with higher risk of obesity and cardiovascular
      disease, and in animals, senescence and life span - a concept encapsulated in the
      postnatal growth acceleration hypothesis. This hypothesis explains the benefits
      of breastfeeding to infants for reduced cardiovascular disease risk in terms of
      their slower early growth and the fetal origins hypothesis in terms of the
      adverse postnatal catch-up growth in infants born small. Early growth, notably
      prior to full term, also influences brain development and cognition - and
      emerging evidence suggests diverse, broader effects, for instance cancer and the
      onset of puberty. Understanding the mechanisms, triggers and windows for such
      effects is important, given the major public health implications, including
      potential new opportunities for primary prevention of adult disease.

PMID- 20139671
TI  - Early infancy as a critical period for development of obesity and related
      conditions.
AB  - The current obesity epidemic has affected even the youngest children in our
      societies, including those in the first months of life. Animal experiments
      suggest that the early postnatal period may be critical to development of
      healthful energy homeostasis and thus prevention of obesity. In humans,
      observational studies and follow-up of randomized feeding trials show that rapid
      weight gain in the first half of infancy predicts later obesity and higher blood
      pressure. Despite the mounting consistency of results, several questions remain
      to be answered before clinical or public health implications are clear. These
      include the need for body composition data in infancy and data from the
      developing world to identify modifiable determinants of gain in adiposity in the
      early weeks of life, to mount interventions to modify these determinants, to
      examine tradeoffs of more vs. less rapid weight gain for different outcomes, and
      to incorporate any interventions that prove to be efficacious into clinical and
      public health practice in a cost-effective manner.

PMID- 20139672
TI  - Leptin, nutrition, and the programming of hypothalamic feeding circuits.
AB  - A large body of epidemiological data suggests that adverse early environments,
      including obesity during pregnancy or early postnatal life, are linked to an
      elevated prevalence of metabolic disease in adult offspring. The mechanisms
      underlying these effects are still poorly understood, but recent data from
      rodents provide insight into a potential role for the brain in this 'metabolic
      programming.' This review summarizes the developmental changes that have been
      observed in the hypothalamus in response to changes in the early nutritional and
      hormonal environment. It also discusses how resetting a diverse array of
      neuroendocrine systems may have long-term effects on the regulation of metabolism
      and energy balance.

PMID- 20139673
TI  - Early growth and ageing.
AB  - Effects of in utero and early life conditions on adult health and disease such as
      cardiovascular disease and type 2 diabetes are well documented by epidemiological
      and clinical observations. Animal models including intrauterine artery ligation,
      maternal restriction of iron, protein or general caloric intake, provide
      invaluable tools to understand mechanisms linking early growth and later diseases
      in adult life. In addition, the rodent model of maternal protein restriction has
      revealed that longevity can be influenced either positively or negatively by
      early growth patterns. Recent rapid advances in the ageing field using model
      organisms involving caloric restriction and genetic mutation as well as gene
      overexpression demonstrated the importance of insulin/ IGF-1 signaling pathways,
      oxidative damage and SIRT1 in the regulation of lifespan. Studies using rodent
      models of maternal protein restriction suggest that alteration in insulin
      metabolism, changes in expression of antioxidant defense systems and in levels of
      oxidative damage (including telomere attrition) may also play a key role in
      regulation of lifespan by the early environment. It is suggested that
      neuroendocrine systems and epigenetic modification may be the potential
      mechanisms underlying beneficial or detrimental effects of early growth on the
      regulation of lifespan. Further studies in this area are warranted.

PMID- 20139674
TI  - Does early growth affect long-term risk factors for cardiovascular disease?
AB  - The concept that early growth and nutrition have long-term biological effects is
      based on extensive studies in animals dating from the 1930s. More recently,
      compelling evidence for a long-term influence, or programming effect, of growth
      has also emerged in humans. Substantial evidence now supports the hypothesis that
      'accelerated' or too fast infant growth increases the propensity to the major
      components of the metabolic syndrome (glucose intolerance, obesity, raised blood
      pressure and dyslipidemia), the clustering of risk factors which predispose to
      cardiovascular morbidity and mortality. The association between infant growth and
      these risk factors is strong, consistent, shows a dose-response effect, and is
      biologically plausible. Moreover, experimental data from prospective randomized
      controlled trials strongly support a causal link between infant growth and later
      cardiovascular risk factors. These observations suggest therefore that the
      primary prevention of cardiovascular disease could begin from as early as the
      first few months of life. The present review considers this evidence, the
      underlying mechanisms involved and its implications for public health.

PMID- 20139675
TI  - Developing world perspective: the importance of growth for short-term health.
AB  - Recently, concern has been raised about the potential adverse long-term
      consequences of rapid child growth. Rapid early childhood weight gain is
      associated with increased likelihood of being overweight or obese later in
      childhood and of having risk factors for the development of chronic disease such
      insulin resistance and elevated blood pressure. This has led to concerns about
      the wisdom of promoting catch-up growth in infants born small for gestational age
      or in children with poor growth after birth. In considering the costs and
      benefits of promoting catch-up growth, we must not lose sight of the immediate
      health threats to children in resource-poor environments in developing countries
      where child morbidity and mortality remain high. The literature on short-term
      consequences of growth is limited by its focus on attained size as an indicator
      of prior nutritional status, but generally shows that children with evidence of
      poor prior growth are at greater risk of morbidity and mortality from common
      infectious diseases, including lower respiratory infections and diarrhea. In
      these settings, failure to promote compensatory growth may have devastating short
      term consequences.

PMID- 20139676
TI  - Postnatal growth and development in the preterm and small for gestational age
      infant.
AB  - A clear relationship exists between undernutrition, poorer growth and poor
      development in term and preterm infants. However, preterm infants are at greater
      risk than term infants. Undernutrition is more common and 'programmed' growth
      rates are almost six times faster. Thus, even short periods of nutritional
      deprivation may have significant effects. Recent advances have led to an
      improvement in early growth but very low birthweight infants remain small for
      gestational age at hospital discharge. Studies suggest that a 'window of
      opportunity' exists after hospital discharge, in that better growth between
      discharge and 2-3 months corrected age is paralleled by better development, and
      poorer growth is associated with poorer development. However, interventions aimed
      at improving growth and development have yielded varying results. This may partly
      be related to differences in study design as well as the composition of the
      nutrient-enriched formulas. Irrespective, one point is concerning, i.e. infant
      boys appear to be at a developmental disadvantage when fed a term infant formula
      after discharge. A single study has also suggested that dietary intervention can
      improve brain growth in term and preterm infants with perinatal brain injury.
      However, concern has been expressed about rapid 'catch-up' growth in preterm
      infants and the development of insulin resistance and visceral adiposity. Data
      from our group do not support the idea of increased or altered adiposity in
      preterm infants fed a nutrient-enriched formula after hospital discharge.

PMID- 20139677
TI  - Interrelationship between growth and development in low and middle income
      countries.
AB  - Early childhood growth failure is a significant public health problem in
      developing countries. We examine relationships between low birthweight and
      stunting with child development. Compared to children born with normal
      birthweight, low birth-weight children have substantially poorer cognitive and
      schooling outcomes later in life. Linear growth failure leading to stunting
      mostly occurs before age 2 years, with stunting in older children reflecting
      growth failure in early life. Many studies show that stunting is associated with
      poor mental and motor development in infants and with low scores in cognitive
      tests, increased frequency of behavioral problems and poor school achievement in
      older children. Very few studies have assessed the relative importance for
      development of prenatal vs. postnatal growth failure and even fewer have done so
      using appropriate statistical techniques. The limited evidence to date suggests
      growth during the first 2 years of life is more important than growth at any
      other time, including the prenatal period, for predicting later cognitive
      development, schooling and educational achievement. In conclusion, children in
      settings of poverty who experience growth failure prior to age 2 years have
      reduced potential to succeed in school and to be productive members of society.

PMID- 20139678
TI  - Role of long-chain polyunsaturated fatty acids in neurodevelopment and growth.
AB  - There has been intense interest in the role of the n-3 long-chain polyunsaturated
      fatty acid (LCPUFA) docosahexaenoic acid (DHA, 22:6n-3), in growth and
      development of infants. In 2009, there are at least twelve published randomized
      controlled trials (RCT) assessing the effects of LCPUFA supplementation of infant
      formula for preterm infants and seventeen RCTs involving formula-fed term
      infants. In addition, at least five RCTs have investigated the effect of DHA
      supplementation during pregnancy and/or lactation on infant and early child
      development. Collectively, the published literature has demonstrated no harm of
      dietary LCPUFA for infants regardless of whether they are born preterm or at
      term. However, developmental benefit is more consistently observed in infants
      born preterm. This may be explained by the fact that DHA accretion to neural
      tissues peaks during the fetal brain growth spurt in the last trimester of
      pregnancy. Infants born preterm are denied the full gestation period to
      accumulate DHA and are at risk of incomplete DHA accumulation. New research is
      focused on the timing and dose of DHA supplementation needed to optimize
      developmental outcomes.

PMID- 20139679
TI  - Growth and development of the brain and impact on cognitive outcomes.
AB  - Understanding human brain development from the fetal life to adulthood is of
      great clinical importance as many neurological and neurobehavioral disorders have
      their origin in early structural and functional cerebral maturation. The
      developing brain is particularly prone to being affected by endogenous and
      exogenous events through the fetal and early postnatal life. The concept of
      'developmental plasticity or disruption of the developmental program' summarizes
      these events. Increases in white matter, which speed up communication between
      brain cells, growing complexity of neuronal networks suggested by gray and white
      matter changes, and environmentally sensitive plasticity are all essential
      aspects in a child's ability to mentalize and maintain the adaptive flexibility
      necessary for achieving high sociocognitive functioning. Advancement in
      neuroimaging has opened up new ways for examining the developing human brain in
      vivo, the study of the effects of early antenatal, perinatal and neonatal events
      on later structural and functional brain development resulting in developmental
      disabilities or developmental resilience. In this review, methods of quantitative
      assessment of human brain development, such as 3D-MRI with image segmentation,
      diffusion tensor imaging to assess connectivity and functional MRI to visualize
      brain function will be presented.

PMID- 20139680
TI  - Benefits and harms of iron supplementation in iron-deficient and iron-sufficient
      children.
AB  - Due to high iron requirements, young children are at risk for iron deficiency
      anemia. Iron supplements are therefore often recommended, especially since iron
      deficiency anemia in children is associated with poor neurodevelopment. However,
      in contrast to most other nutrients, excess iron cannot be excreted by the human
      body and it has recently been suggested that excessive iron supplementation of
      young children may have adverse effects on growth, risk of infections, and even
      on cognitive development. Recent studies support that iron supplements are
      beneficial in iron-deficient children but there is a risk of adverse effects in
      those who are iron replete. In populations with a low prevalence of iron
      deficiency, general supplementation should therefore be avoided. Iron-fortified
      foods can still be generally recommended since they seem to be safer than
      medicinal iron supplements, but the level of iron fortification should be
      limited. General iron supplementation is recommended in areas with a high
      prevalence of iron deficiency, with the exception of malarious areas where a
      cautious supplementation approach needs to be adopted, based either on screening
      or a combination of iron supplements and infection control measures. More studies
      are urgently needed to better determine the risks and benefits of iron
      supplementation and iron-fortified foods given to iron-deficient and iron
      sufficient children.

PMID- 20139681
TI  - Effects of selective dropout on infant growth standards.
AB  - Exclusively breastfed (EBF) infants have higher weight gain during the first 2
      months, and lower thereafter. The explanation for this phenomenon is not clear.
      Longitudinal data from the Social Medical Survey of Children Attending Child
      Health Clinics study with a cohort of 2,151 Dutch children were analyzed
      according to a pattern mixture model. It appears that higher than average growth
      of EBF infants during the first 2 months is primarily attributable to selective
      dropout. Furthermore, between months 2 and 6, light nonEBF infants gain more
      weight than light EBF infants. Both factors aid in explaining differences in
      growth between EBF and nonEBF infants. The WHO Child Growth Standards for weight
      for-age have been calculated from a subgroup of 903 infants (out of 1,743) that
      complied with strict feeding criteria. If similar dropout mechanisms operate in
      the Multicentre Growth Reference Study, then the WHO weight-for-age standards are
      expected to be systematically different from those for the entire group of 1,743
      infants.

PMID- 20139682
TI  - The 2000 Centers for Disease Control and Prevention growth charts: several
      insights after 8 years.
AB  - This paper explores three issues related to the 2000 Centers for Disease Control
      and Prevention growth charts. First, it clarifies the methods that were used to
      create the charts as it has become apparent that the smoothing techniques have
      been somewhat misunderstood. The techniques included smoothing-selected
      percentiles between and including the 3rd and 97th percentiles and then
      approximating these smoothed curves using a procedure to provide the
      transformation parameters, lambda, mu, and sigma. Only the selected percentiles
      were used in this process due to small sample sizes beyond these percentiles.
      Second, given the concern that the infant charts were created with relatively few
      data points in the first few months of life, it compares the original observed
      percentiles with percentiles that include newly available US national data for
      the first few months of life. Third, it discusses the issues that arise if a 99th
      percentile is extrapolated based on the lambda, mu, and sigma parameters. The
      99th percentile of the body mass index-for-age chart has been recommended to
      identify extremely obese children, yet the 97th percentile is the highest
      available percentile on the Centers for Disease Control and Prevention growth
      charts.

PMID- 20139683
TI  - Growth charts compared.
AB  - Growth assessment of children requires comparison of growth measurements with
      normative references, usually in the form of growth charts. Traditionally growth
      charts (growth references) have described the growth of children who were
      considered normal and were living in a defined geographic area. The new WHO
      growth charts, on the other hand, are growth standards that aim to represent
      growth as it occurs worldwide. Moreover, they represent growth as it occurs under
      optimal circumstances and is thought to be conducive to optimal long-term health.
      Most growth references are single-country references, exemplified here by charts
      from the UK, the Netherlands and the USA. By contrast, the Euro-Growth reference
      and the WHO standard are based on multinational samples. Comparison of these five
      charts reveals surprisingly large differences that are for the most part
      unexplained. Differences between the WHO charts and other charts are only
      partially explained by the use of a prescriptive approach and by the data
      truncation employed. The large differences between charts probably are of merely
      trivial consequence when charts are used in monitoring individual children. When
      charts are used in health assessment of groups of children, the impact of the
      differences, however, is substantial.

PMID- 20139684
TI  - Body composition in infancy: impact on health later in life.
AB  - From retrospective studies, there is substantial evidence that birthweight and
      the rate of weight gain during early infancy are associated with increased risk
      for adverse health outcomes later in life. Birthweight is the marker of the
      integrative effects of the prenatal environment, while the rate of weight gain
      after birth reflects both genetic potential and external postnatal influences.
      The adulthood-to-infancy associations constitute the basis for the 'fetal
      origins' and 'catch-up growth' hypotheses for some diseases. However, these
      findings are based on the assumption that anthropometric-based indices reflect
      body composition during both time periods, with the body mass index
      (weight/stature2) being the most frequently used index. More direct measures of
      body composition were simply not available at the time of the births of the
      adults participating in these studies. Nowadays, there are a number of in vivo
      techniques that can be used to examine body composition in infancy. In
      particular, what does the body mass index reflect in terms of body composition
      for the infant? Is it an adequate index?

PMID- 20139685
TI  - Endocrinology of growth.
AB  - Growth is a remarkably complex biological phenomenon, requiring the coordinated
      production of multiple hormones and growth factors. Human growth is characterized
      by several distinct features, including: (1) rapid growth in late gestation; (2)
      growth deceleration immediately following birth; (3) a prolonged childhood and a
      mid-childhood growth spurt; (4) a pubertal growth spurt; (5) relatively late
      attainment of adult height, and (6) minimal sexual dimorphism of adult stature.
      Secular changes in the height of humans probably reflect nutritional and
      environmental factors, rather than major genomic changes. While multiple hormones
      impact growth, the growth hormone (GH)-insulin-like growth factor (IGF) axis
      plays a central role in both intrauterine and postnatal growth. GH, after being
      secreted by the pituitary, binds to a transmembrane receptor and activates a
      postreceptor signaling cascade, ultimately leading to phosphorylation of signal
      transducer and activator of transcription (STAT) 5b. STAT5b transcriptionally
      regulates the genes for IGF-I and for key IGF-binding proteins. IGF-I, in turn,
      binds to the type 1 IGF receptor, resulting in chondrocyte proliferation and
      statural growth. IGF-deficient states may be divided into secondary forms,
      reflecting defects in GH production, and primary forms. Molecular defects of the
      GH-IGF axis have been identified in humans, with phenotypes that correspond to
      the specific genetic lesions. Therapy with GH or IGF-I can now be matched to
      specific defects in the GH-IGF axis.

PMID- 20139686
TI  - [Bronchial asthma in adult].

PMID- 20139687
TI  - [Bronchial asthma in children].

PMID- 20139688
TI  - [Features and molecular mechanisms of nucleic acid adjuvants].

PMID- 20139689
TI  - [Immunological tolerance and allergy].

PMID- 20139690
TI  - [Investigation of factors childhood asthma persisting into adulthood].
AB  - BACKGROUND: A questionnaire survey was conducted to determine the percentages of
      patients with childhood-onset asthma persisting into adulthood and adult-relapse
      asthma in the adult asthmatic population, and to identify the factors the
      childhood-onset asthma persisting into adulthood. METHODS: The questionnaire
      survey included 822 adult asthmatic patients who visited out patient clinic at
      Nishikata Hospital. The characteristics of the three groups of adult asthmatics,
      namely, the childhood-onset asthma persisting into adulthood, adult-onset asthma
      and adult-relapse asthma, were compared with those of a group of 153 pediatric
      asthma patients with remission (control group). RESULTS: 1) The numbers of
      patients with adult-onset asthma, childhood-onset asthma persisting into
      adulthood and adult-relapse asthma in the survey population were 531 (64.7%), 168
      (20.4%) and 123 (14.9%), respectively. 2) Comparison of the characteristics of
      the two groups of adult asthmatics (childhood-onset asthma persisting into
      adulthood and adult-relapse asthma) and control group revealed that the average
      age at onset and percentage of patients with a history of without preventive
      treatment, and delay in the start of early interventions were higher in the
      former groups than in the control group (p<0.01). Furthermore, the frequencies of
      severe asthma were significantly higher in the patients with childhood-onset
      asthma persisting into adulthood than in control group (p<0.01). The percentage
      of smokers was higher in the adult-relapse asthma group and childhood-onset
      asthma persisting into adulthood group than in control group. CONCLUSION: 1) In
      this adult asthmatic study population, the percentages of childhood-onset asthma
      persisting into adulthood and adult-relapse asthma in adult asthmatic population
      were 35.3%. 2) To prevent persistence of childhood-onset asthma into adulthood,
      it is important to prevent smoking, not keeping pets, and not delay in the onset
      of early interventions in childhood.

PMID- 20139691
TI  - [Survey of asthma control and anti-asthma medication use among Japanese adult
      patients].
AB  - BACKGROUND: The purpose of this study was to clarify disease control and
      medication use among Japanese adult asthmatic patients. METHOD: We studied the
      reality of adult outpatients and inpatients with asthma at 26 national hospitals
      across Japan who visited the clinic between September and October 2006. Anti
      asthma medication use and asthma control were assessed. Disease severity was
      determined according to the 2006 Japanese Guideline. The results of this study
      were compared with those obtained in 1995 after standardization by age and
      gender. RESULTS: Of 2524 patients, the prevalence of inhaled corticosteroid use
      in 2006 was 89%, which was higher than that in 1995 (62%). Although the
      prevalence of patients who experienced asthma hospitalization once or more in
      their lifetime in 1995 was 73%, that in 2006 decreased to 49%. The prevalences of
      hospitalization and unscheduled doctor visit in the last 12 months in 2006 were
      8% and 25% respectively. The percentage of patients in 2006 who did not reach an
      acceptable level of control despite treatment at step 4 of the 2006 Japanese
      guideline was 15%. CONCLUSIONS: A favorable change in asthma medication use and
      asthma control was observed from 1995 to 2006; that is, increased prevalence of
      inhaled corticosteroid use and decreased prevalence of patients who experienced
      hospitalization for asthma once or more in their lifetime. However, some patients
      remained symptomatic despite high-dose inhaled corticosteroid treatment.

PMID- 20139692
TI  - [Regional differences in the prevalence of Japanese cedar-pollen allergy].
AB  - PURPOSE: According to the 2008 survey conducted by Baba et al., the average
      prevalence of Japanese cedar-pollen allergy is 26.5% in Japan, although there are
      great regional differences in the prevalence of this disease. In this study, we
      investigated the causes of its regional differences. METHODS: Regional
      differences in the 2008 prevalence of cedar-pollen allergy in 47 prefectures,
      obtained by Baba et al., were examined in terms of the correlations with the
      following factors: mean cedar pollen count in each region, the pollen dispersal
      period, relative humidity in February and March, and the concentrations of SPM,
      NOx and Ox. The pollen counts of cedar and cypress and the sum of these pollen
      counts were also measured. RESULTS: The prevalence of cedar-pollen allergy had
      the highest correlation with the pollen dispersal period, followed by the
      correlation with the pollen count and relative humidity in the order. There was
      no statistically significant correlation between the prevalence of cedar-pollen
      allergy and air pollutants such as SPM.

PMID- 20139693
TI  - [A case of an allergic reaction due to Anisakis simplex after the ingestion of
      salted fish guts made of Sagittated calamari: allergen analysis with recombinant
      and purified Anisakis simplex allergens].
AB  - A 75-year-old man ingested salted fish guts made of Sagittated calamari which he
      caught in the daytime, with alcohol and then dozed. Five hours later, he woke up
      due to itching over his entire body and noticed generalized urticaria and a
      swollen tongue, which was too large for him to close his mouth. Serum total IgE
      was 456 IU/ml and ImmunoCAP was positive for anisakis, but negative for squid,
      shrimp, and ascaris. A skin prick test (SPT) was positive for anisakis extract
      (10 mg/ml) and house dust mites, but negative for squid and shrimp. He was
      diagnosed with IgE-mediated allergy due to Anisakis simplex after the ingestion
      of salted fish guts made of Sagittated calamari, which had been parasitized by
      Anisakis simplex. Furthermore, we performed SPT with six extracts of purified or
      recombinant allergens (Ani s 1, 3, 4, 5, 6, and 8) to identify the causative
      allergens in this case. Only Ani s 3 (tropomyosin) was positive, indicating that
      Ani s 3 was the causative allergen in this case. Third stage larvae of the
      nematode Anisakis simplex often parasitize not only marine fish but also
      invertebrates, including squid. It is necessary to consider Anisakis simplex
      allergy for urticarial reactions that develop after the ingestion of squid.

PMID- 20139694
TI  - Integrin signaling and lung cancer.
AB  - The poor prognosis of most non small cell lung carcinomas is due to their ability
      to efficiently invade surrounding tissues and blood vessels, finally
      metastasizing to distant organs. Integrin mediated adhesive interaction with the
      surrounding extracellular matrix is a key limiting step in the regulation of the
      invasive properties of several cancer cell types. Here, we examine the rising
      evidences about the role that integrins can play in the physiopathology of non
      small cell lung carcinomas by regulating cell adhesion as well as the activation
      of growth factors and the traffic of their cognate receptors. Modulation of the
      signaling pathways controlled by integrins in lung cancer cells might offer the
      opportunity to design and develop new drugs that might be successfully combined
      with conventional chemotherapy and radiotherapy.

PMID- 20139695
TI  - An up to date look at lung cancer screening.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. At the time
      of initial presentation, most patients are at an advance stage of disease and
      have a poor associated prognosis. Those diagnosed and treated at earlier stages
      have a significantly better outcome with 5-year survival for stage I disease
      approaching 75%. Ideally a screening strategy for lung cancer would detect
      disease at an earlier stage and allow for potential surgical cure. The purpose of
      this review is to examine past and current evidence as it relates to lung cancer
      screening.

PMID- 20139696
TI  - MET molecular mechanisms and therapies in lung cancer.
AB  - The MET tyrosine kinase signaling pathway is upregulated in many cancers,
      including lung cancer. The pathway normally promotes mitosis, cell motility and
      cell survival; but in cancer it can also promote cell proliferation, invasion,
      metastasis and angiogenesis. The activating ligand, hepatocyte growth factor
      (HGF) is normally secreted by fibroblasts and smooth muscle cells, but can also
      be produced by tumor cells. MET upregulation in lung cancer is caused by
      overexpression and mutation. These mutations can vary with ethnicity. MET
      signaling affects cytoskeletal proteins such as paxillin, which participates in
      cell adhesion, growth and motility. Therapeutic approaches that block MET
      signaling are being studied, and include the use of: small interference RNA,
      Geldanamycin, competitive HGF homologues, decoy receptors and direct MET
      inhibitors such as K252a, SU11274, PHA665752 and PF2341066. It is hoped that
      blocking MET signaling may one day become an effective treatment for some lung
      cancers.

PMID- 20139697
TI  - Role of cell cycle regulators in lung carcinogenesis.
AB  - Cellular division is an ordered, tightly regulated process involving multiple
      checkpoints that assess extracellular growth signals, cell size and DNA
      integrity. Progression throughout the cell cycle is based on the activation of
      different CDK-cyclin complexes that prevent cells from entering into a new phase
      until thay have successfully complete the previous one. In addition, a series of
      cell cycle checkpoints are designed to preserve genome integrity and chromosomal
      stability. Neoplastic lung cells develop the ability to bypass several of these
      checkpoints, and tumor cell proliferation is frequently associated with genetic
      or epigenetic alterations in key regulators of the cell cycle. The goal of this
      review is to summarize the knowledge about the dysregulation of major cell cycle
      regulators in lung cancer pathogenesis and to discuss the use of these proteins
      as targets for therapeutic intervention.

PMID- 20139698
TI  - Lung cancer: a modified epigenome.
AB  - Epigenetic is the study of heritable changes in gene expression that occur
      without changes in DNA sequence. This process is important for gene expression
      and genome stability and its disruption is now thought to play a key role in the
      onset and progression of numerous tumor types. The most studied epigenetic
      phenomena includes post-translational modifications in DNA and histone proteins
      as well as microRN As expression. As epigenetic aberrations are potentially
      reversible, their correction has emerged as a potential strategy for the
      treatment of cancer. This review highlights the roles of chromatin epigenetic
      modifications and of microRN As expression in lung tumorigenesis and discusses
      the emerging epigenetic therapies which are being developed for the treatment of
      lung cancer.

PMID- 20139700
TI  - Second international conference on F-BAR proteins: October 1-3, 2009 at Ranas
      Slott, Sweden.

PMID- 20139699
TI  - Guidance molecules in lung cancer.
AB  - Guidance molecules were first described in the nervous system to control axon
      outgrowth direction. They are also widely expressed outside the nervous system
      where they control cell migration, tissue development and establishment of the
      vascular network. In addition, they are involved in cancer development, tumor
      angiogenesis and metastasis. This review is primarily focused on their functions
      in lung cancer and their involvement in lung development is also presented. Five
      guidance molecule families and their corresponding receptors are described,
      including the semaphorins/neuropilins/plexins, ephrins and Eph receptors,
      netrin/DCC/UNC5, Slit/Robo and Notch/Delta. In addition, the possibility to
      target these molecules as a therapeutic approach in cancer is discussed.

PMID- 20139702
TI  - Harnessing Listeria monocytogenes to target tumors.
AB  - Because of its cytosolic localization, Listeria monocytogenes (LM) has long been
      considered an attractive tool for delivering tumor-associated antigens (TAA)
      antigens in vivo to combat cancer. LM directly infects antigen-presenting cells
      (APC) such as monocytes, macrophages and dendritic cells (DC), thereby delivering
      the TAA into their cytoplasm, resulting in processing, and presentation of the
      antigen to the immune system. This activates adaptive and innate immune responses
      to the TAA, mediating tumor cell cytolysis. Recently we discovered additional
      pathways by which Listeria can be harnessed to induce tumor cell death, which
      suggest new directions in the development of vaccines or therapies against
      cancer. In one approach, we have used Listeria to induce immune responses that
      destroy tumor vasculature. Another new pathway involves selective infection of
      cancer cells with Listeria, followed by tumor cell death through the production
      of high levels of reactive oxygen species (ROS) and through Listeria-specific
      cytotoxic T lymphocytes (CTL). This review will focus on the most recent studies
      on the multiple pathways of LM and how they can be harnessed in the battle
      against cancer. 

PMID- 20139701
TI  - Chromosomal and genomic changes in lung cancer.
AB  - Lung cancer is a complex spectrum of diseases characterized by extensive genomic
      instability, which can be detected among both histological subtypes and different
      foci within a tumor. Conventional and cutting edge investigative technologies
      have uncovered scores of genomic changes in individual specimens that have been
      used to characterize specific molecular subtypes. Oncogenes with predominant
      roles in lung cancer include EGFR, MYC and RAS family members, PIK3CA, NKX2-1 and
      ALK; tumor suppressor genes include TP53, RB1, CDKN2, and a cluster of genes
      mapped at 3p. MicroRNA regulators also have been linked to lung cancer. The
      functional role of the recurrent genomic changes in lung tumors has been
      explored, which has led to a better understanding of cell growth, differentiation
      and apoptotic pathways. Additionally, this knowledge has supported the
      development of novel therapeutics and translational tools for selection of
      patients for personalized therapy.

PMID- 20139703
TI  - Refining methylation-targeting therapies for pancreatic cancer-focusing on DNMT1.

PMID- 20139704
TI  - Bone-specific growth inhibition of prostate cancer metastasis by atrasentan.
AB  - Advanced prostate cancer frequently metastasizes to bone and remains an incurable
      disease. One recent experimental therapy involves endothelin receptor A (ETA)
      antagonists (e.g., atrasentan). Clinical results to date have been mixed, with
      atrasentan not meeting its primary endpoints in a Phase III trial. It remains an
      open question whether some patients might benefit from this therapy, while others
      may not. Preclinical data supports the concept that the endothelin signaling axis
      may be particularly important for tumor growth in bone, but the extent to which
      it is involved in metastatic colonization of other organ sites in prostate cancer
      remains unclear. Here we evaluate the efficacy of atrasentan in a mouse model of
      prostate cancer metastatic colonization. Using bioluminescence imaging, we show
      that atrasentan does inhibit tumor growth in, but not the initial colonization
      of, bony sites in intracardially-injected 22Rv1 prostate cancer cells. However,
      atrasentan shows little efficacy in soft tissues such as adrenal gland or liver.
      Our studies show that whether atrasentan exhibits significant overall antitumor
      efficacy and survival benefit depends on the presence of bone metastasis evident
      in that animal. Though in contrast to previous findings efficacy is apparent in a
      prostate tumor model that elicits mixed osteoblastic/osteolytic lesions. These
      data confirm the notion that atrasentan may exhibit selective activity against
      prostate cancer bone metastasis, mirroring clinical findings, and suggest that
      the role of endothelin signaling in bone metastasis may be more complex than
      previously appreciated. The model described here may provide a valuable tool for
      unraveling this complexity.

PMID- 20139705
TI  - ZD6474, a dual tyrosine kinase inhibitor of EGFR and VEGFR-2, inhibits MAPK/ERK
      and AKT/PI3-K and induces apoptosis in breast cancer cells.
AB  - Abnormalities in gene expression and signaling pathways downstream of the
      epidermal growth factor receptor (EGFR) and vascular endothelial growth factor
      receptor (VEGFR) contribute to the progression, invasion, and maintenance of the
      malignant phenotype in human cancers, including breast. Consequently, the dual
      kinase inhibitor of EGFR and VEGFR ZD6474 represents a promising biologically
      based treatment that is currently undergoing clinical trials for non-small cell
      lung cancer. Patients suffering from breast cancers have a poor prognosis because
      of the lack of effective agents and treatment strategies. We hypothesized that
      inhibition of phosphorylation of the EGFR and VEGFR by ZD6474 would inhibit
      breast cancer cell proliferation and induce apoptosis. This hypothesis was tested
      using human breast cancer cell lines. ZD6474 inhibited cell proliferation in a
      dose-dependent manner, by blocking cell progression at the G(0)-G(1) stage,
      through downregulation of expression of cyclin D1 and cyclin E. In vitro, ZD6474
      inhibited growth factor-induced phosphorylation of EGFR, VEGFR-2, MAPK and Akt.
      ZD6474 also downregulated anti-apoptotic markers including Bcl-2, upregulated pro
      apoptotic signaling events involving expression of bax, activation of caspase-3,
      and induction of poly (ADP-ribose) polymerase during apoptosis. ZD6474 inhibited
      anchorage independent colony formation using soft agar assays, and invasion of
      breast cancer cells in vitro using Boyden chamber assays. In a xenograft model
      using human MDA-MB-231 breast cancer cells, ZD6474 inhibited tumor growth and
      induced cancer-specific apoptosis. Collectively, these data imply that ZD6474 a
      dual kinase inhibitor has potential for the targeted therapy of breast cancer.

PMID- 20139706
TI  - Helical motion of an S4 voltage sensor revealed by gating pore currents.
AB  - The mechanism by which the voltage sensors of voltage-gated ion channels move
      gating charge during the activation process is a subject of active debate. In
      this issue of Channels, Gamal El-Din et al. probe the movements of the S4 voltage
      sensor of Shaker K(+) channels through clever use of omega gating pore currents
      generated by paired gating-charge mutations. Their results provide strong support
      for a sliding helix or helical screw mechanism of gating charge movement.

PMID- 20139707
TI  - Changes in intra-luminal calcium during spontaneous calcium waves following
      sensitization of ryanodine receptor channels.
AB  - Cardiac contraction during systole is dependent on action potential-triggered
      Ca(2+) release from the sarcoplasmic reticulum (SR) through ryanodine receptor
      (RyR) channels. SR Ca(2+) release can also occur spontaneously during diastole,
      which causes a decrease in Ca(2+) content within the SR and contributes to
      arrhythmogenesis. Here, we use measurements of cytosolic Ca(2+) and intra-SR
      Ca(2+) ([Ca(2+)](SR)) to examine how RyR sensitization alters spontaneous SR
      Ca(2+) release events in rabbit ventricular myocytes. RyR sensitization with
      caffeine (250 microM) increased the open probability of single RyR channels,
      increased the initial frequency and amplitude of local SR Ca(2+) release events
      (Ca(2+) sparks), and decreased the [Ca(2+)](SR) level where Ca(2+) sparks
      terminated. In intact myocytes, caffeine applied during rest after steady-state
      electrical stimulation increased the frequency of spontaneous Ca(2+) waves and
      decreased the [Ca(2+)](SR) level where waves terminated. These effects caused a
      marked loss of SR Ca(2+) content. Therefore, increasing RyR activity has complex
      effects on cardiac function. Increased RyR activity during systole is beneficial
      as it increases SR Ca(2+) release and contractile strength. However, increased
      RyR activity during diastole produces spontaneous, arrhythmogenic Ca(2+) release
      events that lower SR Ca(2+) content and subsequently decrease contractility.

PMID- 20139708
TI  - K(V)4.2 channels tagged in the S1-S2 loop for alpha-bungarotoxin binding provide
      a new tool for studies of channel expression and localization.
AB  - We report the first successful insertion of an engineered, high-affinity alpha
      bungarotoxin (Bgtx) binding site into a voltage-gated ion channel, K(V)4.2, using
      a short, intra-protein embedded sequence (GGWRYYESSLEPYPDGG), derived from a
      previously described mimotope peptide, HAP. A major benefit to this approach is
      the ability to live-image the distribution and fate of functional channels on the
      plasma membrane surface. The Bgtx binding sequence was introduced into the
      putative extracellular loop between the S1 and S2 transmembrane domains of
      K(V)4.2. Following co-expression with KChIP3 in tsA201 cells, S1-S2 HAP-tagged
      channels express at levels comparable to wild-type K(V)4.2, and their activation
      and inactivation kinetics are minimally altered under most conditions. Binding
      assays, as well as live staining of surface-expressed K(V)4.2 channels with
      fluorescent-Bgtx, readily demonstrate specific binding of Bgtx to HAP-tagged
      K(V)4.2 expressed on the surface of tsA201 cells. Similar live-imaging results
      were obtained with HAP-tagged K(V)4.2 transfected into hippocampal neurons in
      primary culture suggesting applicability for future in vivo studies. Furthermore,
      the activation kinetics of S1-S2-tagged K(V)4.2 channels are minimally affected
      by the binding of Bgtx, suggesting a limited role if any for the S1-S2 loop in
      voltage sensing or gating associated conformational changes. Successful
      functional insertion of the HAP sequence into the S1-S2 linker of K(V)4.2
      suggests that other related channels may similarly be amenable to this tagging
      strategy.

PMID- 20139710
TI  - Further analysis of counterion permeation through anion-selective glycine
      receptor channels.
AB  - The functional role of ion channels, which allow counterion permeation, depends
      critically on their relative anion-cation relative selectivity. From whole-cell
      patch clamp reversal potential measurements under dilution potential conditions,
      we have already shown that anion-cation permeabilities of anion-selective wild
      type (WT) and mutant (with larger pore diameter) glycine receptor (GlyR) channels
      in the presence of Li(+), Na(+) and Cs(+) counterions, were inversely correlated
      with the equivalent hydration diameter of the counterion, with chloride-cation
      permeability increasing as counterion equivalent hydration diameter increased
      with respect to the channel minimum pore diameter. Corrected for liquid junction
      potentials (LJPs; using ion activities), the previous chloride-cation
      permeabilities for the alkali cations were 23.4 (Li(+)), 10.9 (Na(+)) and 5.0
      (Cs(+)) for the smaller WT channel. Further analysis to incorporate an initial
      offset potential correction, to fully allow for slight differences between
      internal cell composition and external control salt solution, changed the above
      permeability ratios to 30.6 (Li(+)), 11.8 (Na(+)) and 5.0 (Cs(+)), adding
      enhanced support for the inverse correlation between anion-to-counterion
      permeability ratio and equivalent hydrated counterion diameter relative to
      channel pore diameter (erroneously ignoring LJPs reduces each permeability ratio
      to about 4). Also, new direct measurements of LJPs (for NaCl and LiCl salt
      dilutions) using a 3M KCl-agar reference salt bridge (with freshly-cut end for
      each solution composition change) have shown excellent agreement with calculated
      LJPs (using ion activities), validating calculated LJP values. We continue to
      suggest that counterion cations permeate with chloride ions as neutral pairs.

PMID- 20139709
TI  - KCNQ1/KCNE1 assembly, co-translation not required.
AB  - Voltage-gated potassium channels are often assembled with accessory proteins that
      increase their functional diversity. KCNE proteins are small accessory proteins
      that modulate voltage-gated potassium (K(V)) channels. Although the functional
      effects of various KCNE proteins have been described, many questions remain
      regarding their assembly with the pore-forming subunits. For example, while
      previous experiments with some K(V) channels suggest that the association of the
      pore-subunit with the accessory subunits occurs co-translationally in the
      endoplasmic reticulum, it is not known whether KCNQ1 assembly with KCNE1 occurs
      in a similar manner to generate the medically important cardiac slow delayed
      rectifier current (I(Ks)). In this study we used a novel approach to demonstrate
      that purified recombinant human KCNE1 protein (prKCNE1) modulates KCNQ1 channels
      heterologously expressed in Xenopus oocytes resulting in generation of I(Ks).
      Incubation of KCNQ1-expressing oocytes with cycloheximide did not prevent I(Ks)
      expression following prKCNE1 injection. By contrast, incubation with brefeldin A
      prevented KCNQ1 modulation by prKCNE1. Moreover, injection of the trafficking
      deficient KCNE1-L51H reduced KCNQ1 currents. Together, these observations
      indicate that while assembly of KCNE1 with KCNQ1 does not require co-translation,
      functional KCNQ1-prKCNE1 channels assemble early in the secretory pathway and
      reach the plasma membrane via vesicular trafficking.

PMID- 20139711
TI  - Targeted gene replacement by homologous recombination in Drosophila stimulates
      production of second-site mutations.
AB  - Gene replacement by homologous recombination is a powerful technique for
      generating mutations in Drosophila. while using this technique for the BEAF gene,
      we encountered non-targeted lethal mutations on the target chromosome that
      complicated the analysis of the BEAF mutations until they were discovered and
      removed by meiotic recombination. Subsequent experiments indicated that the gene
      targeting method leads to a modest but significant three-fold increase in the
      rate of production of non-targeted lethal mutations. It is important to be aware
      of this phenomenon when using this method.

PMID- 20139712
TI  - The past, present and future of gene targeting in Drosophila.
AB  - The beginnings of Drosophila as a model organism reach far back into the 1900s to
      Thomas Hunt Morgan's first fly room. The success of this system for the study of
      genetics is closely linked to the fact that the fly is amenable to complex
      genetic manipulations so that random mutagenesis screens can be easily performed.
      Nonetheless, current advances in genomics and in our ability to predict protein
      function emphasize the importance of mutagenesis methods that are not random, but
      rather give the researcher control over how the gene is modified. Gene targeting
      in Drosophila, developed almost a decade ago, makes use of the organism's own DNA
      repair machinery to exchange genetic information between a chromosomal target and
      an exogenous template. Here we discuss available targeting methods and recent
      advances that facilitate repeated targeting and open the doors to routine allelic
      studies.

PMID- 20139713
TI  - Proteome profiling reveals tissue-specific protein expression in the male
      reproductive system of Drosophila melanogaster.
AB  - The reproductive systems of male and female Drosophila have been well studied
      genetically and cytologically because of the importance of meiotic mechanisms in
      understanding inheritance and speciation. Recently, there has been increasing
      interest in proteomics of Drosophila melanogaster, because detailed and
      comprehensive gene annotations have made it straightforward to identify proteins
      analyzed by mass spectrometry. We have applied proteomic analysis to the male
      reproductive system with the aim of understanding sperm maturation not only
      during the process of spermatogenesis, but also during the movement of sperm from
      the seminal vesicle through the male reproductive system and into the uterus
      following copulation. In this article, we will provide an overview of the
      principles of recent proteomic technologies and describe a few proteomic profiles
      of the male reproductive organs.

PMID- 20139714
TI  - Fragment molecular orbital calculations reveal that the E200K mutation markedly
      alters local structural stability in the human prion protein.
AB  - The E200K mutation of the human prion protein (PrP) is known to cause familial
      Creutzfeldt-Jakob disease. In order to elucidate the effects of the mutation on
      the local structural stability of PrP, we performed ab initio fragment molecular
      orbital calculations for the wild-type human PrP and the E200K variant modeled
      under neutral and mild acidic conditions. The calculations revealed that this
      substitution markedly altered the intramolecular interactions in the PrP,
      suggesting that the local structural instabilities induced by the E200K mutation
      might cause initial denaturation of the PrP and its subsequent conversion to a
      pathogenic form. This work presents a new approach for quantitatively elucidating
      structural instabilities in proteins that cause misfolding diseases.

PMID- 20139715
TI  - Comparative and functional analysis of the archaeal cell cycle.
AB  - The temporal and spatial organization of the chromosome replication, genome
      segregation and cell division processes is less well understood in species
      belonging to the Archaea, than in those from the Bacteria and Eukarya domains.
      Novel insights into the regulation and key components of the Sulfolobus
      acidocaldarius cell cycle have been obtained through genome-wide analysis of cell
      cycle-specific gene expression, followed by cloning and characterization of gene
      products expressed at different cell cycle stages. Here, the results of the
      transcript profiling are further explored, and potential key players in archaeal
      cell cycle progression are highlighted in an evolutionary context, by comparing
      gene expression patterns and gene conservation between three selected microbial
      species from different domains of life. We draw attention to novel putative
      nucleases and helicases implicated in DNA replication, recombination and repair,
      as well as to potential genome segregation factors. Focus is also placed upon
      regulatory features, including transcription factors and protein kinases inferred
      to be involved in the execution of specific cell cycle stages, and regulation
      through metabolic coupling is discussed.

PMID- 20139716
TI  - Calorie restriction: decelerating mTOR-driven aging from cells to organisms
      (including humans).
AB  - Although it has been known since 1917 that calorie restriction (CR) decelerates
      aging, the topic remains highly controversial. What might be the reason? Here I
      discuss that the anti-aging effect of CR rules out accumulation of DNA damage and
      failure of maintenance as a cause of aging. Instead, it suggests that aging is
      driven in part by the nutrient-sensing TOR (target of rapamycin) network. CR
      deactivates the TOR pathway, thus slowing aging and delaying diseases of aging.
      Humans are not an exception and CR must increase both maximal and healthy
      lifespan in humans to the same degree as it does in other mammals. Unlike mice,
      however, humans benefit from medical care, which prolongs lifespan despite
      accelerated aging in non-restricted individuals. Therefore in humans the effect
      of CR may be somewhat blunted. Still how much does CR extend human lifespan? And
      could this extension be surpassed by gerosuppressants such as rapamycin?

PMID- 20139717
TI  - Biological impact of freezing Plk1 in its inactive conformation in cancer cells.
AB  - Human polo-like kinase 1 (Plk1), a key regulator of mitosis, is overexpressed in
      various human tumors. It is a negative prognostic factor for cancer patients and
      a measure for the aggressiveness of a tumor. Thus, targeting Plk1 might be a
      promising approach for cancer therapy. Kinase inhibitors are divided in type I
      inhibitors, targeting the highly conserved active conformation, and the more
      selective type II inhibitors, targeting the inactive conformation of kinases. We
      analyzed our previously identified type II Plk1 inhibitor SBE13 which is able to
      inhibit Plk1 activity. To determine its ability to induce cell death in cancer
      cells, we applied kinase assays, western blot analyses, FACScan analyses, Caspase
      assays and immunofluorescence studies. We detected decreased cell proliferation,
      delayed progression through the cell cycle in lower SBE13 concentrations, a
      G(2)/M arrest using higher SBE13 concentrations followed by apoptosis, and
      abnormal mitotic figures. Notably, SBE13 did not influence activity of other
      kinases (Plk2, Plk3, Aurora A), indicating the selectivity of this type II Plk1
      inhibitor. This study suggests that Plk1 kinase inhibitors targeting the inactive
      conformation of Plk1 may be considered for the development of cancer
      therapeutics.

PMID- 20139718
TI  - 26S proteasome exhibits endoribonuclease activity controlled by extra-cellular
      stimuli.
AB  - 26S proteasome is a large multi-subunit protein complex involved in proteolytic
      degradation of proteins. In addition to its canonical proteolytic activity, the
      proteasome is also associated with recently characterized endoribonuclease (endo-
      RNAse) activity. However, neither functional significance, nor the mechanisms of
      its regulation are currently known. In this report, we show that 26S proteasome
      is able to hydrolyze various cellular RNAs, including AU-rich mRNA of c-myc and c
      fos. The endonucleolytic degradation of these mRNAs is exerted by one of the 26S
      proteasome subunits, PSMA5 (alpha5). The RNAse activity of 26S proteasome is
      differentially affected by various extra-cellular signals. Moreover, this
      activity contributes to the process of degradation of c-myc mRNA during induced
      differentiation of K562 cells, and may be controlled by phosphorylation of the
      adjacent subunits, PSMA1 (alpha6) and PSMA3 (alpha7). Collectively, the data
      presented in this report suggest a causal link between cell signalling pathways,
      endo-RNAse activity of the 26S proteasome complex and metabolism of cellular
      RNAs.

PMID- 20139719
TI  - Mitogen activated protein kinase phosphatases and cancer.
AB  - Deregulation of cell signaling is a vital part of cancer development. The mitogen
      activated protein kinase (MAPK) family is involved in regulating both cell growth
      and cell death. This family of kinases is negatively regulated by mitogen
      activated protein kinase phosphatases (MKPs). MKPs are dual specificity
      phosphatases that target threonine and tyrosine residues that appear in a TXY
      motif. There are eleven members of the MKP family. Expression of MKPs has been
      shown to be altered in many different types of cancer. Most of what is known
      centers on MKP-1, MKP-2 and MKP-3. This review will focus on their role in cancer
      development and progression.

PMID- 20139720
TI  - Adenovirus RIDalpha protein reveals novel autophagic mechanism that regulates
      cholesterol homeostasis.

PMID- 20139721
TI  - MicroRNAs and metastases--the neuroblastoma link.

PMID- 20139722
TI  - An allosteric Akt inhibitor effectively blocks Akt signaling and tumor growth
      with only transient effects on glucose and insulin levels in vivo.
AB  - The PI3K-Akt pathway is dysregulated in the majority of solid tumors.
      Pharmacological inhibition of Akt is a promising strategy for treating tumors
      resistant to growth factor receptor antagonists due to mutations in PI3K or PTEN.
      We have developed allosteric, isozyme-specific inhibitors of Akt activity and
      activation, as well as ex vivo kinase assays to measure inhibition of individual
      Akt isozymes in tissues. Here we describe the relationship between PK, Akt
      inhibition, hyperglycemia and tumor efficacy for a selective inhibitor of Akt1
      and Akt2 (AKTi). In nude mice, AKTi treatment caused transient insulin resistance
      and reversible, dose-dependent hyperglycemia and hyperinsulinemia. Akt1 and Akt2
      phosphorylation was inhibited in mouse lung with EC50 values of 1.6 and 7 MUM,
      respectively, and with similar potency in other tissues and xenograft tumors.
      Weekly subcutaneous dosing of AKTi resulted in dose-dependent inhibition of LNCaP
      prostate cancer xenografts, an AR-dependent tumor with PTEN deletion and
      constitutively activated Akt. Complete tumor growth inhibition was achieved at
      200 mpk, a dose that maintained inhibition of Akt1 and Akt2 of greater than 80%
      and 50%, respectively, for at least 12 hours in xenograft tumor and mouse lung.
      Hyperglycemia could be controlled by reducing C(max), while maintaining efficacy
      in the LNCaP model, but not by insulin administration. AKTi treatment was well
      tolerated, without weight loss or gross toxicities. These studies supported the
      rationale for clinical development of allosteric Akt inhibitors and provide the
      basis for further refining of pharmacokinetic properties and dosing regimens of
      this class of inhibitors.

PMID- 20139723
TI  - CEP215 is involved in the dynein-dependent accumulation of pericentriolar matrix
      proteins for spindle pole formation.
AB  - CEP 215 is a human orthologue of Drosophila centrosomin which is a core
      centrosome component for the pericentriolar matrix protein recruitment. Recent
      investigations revealed that CEP 215 is required for centrosome cohesion,
      centrosomal attachment of the gamma-TuRC, and microtubule dynamics. However, it
      remains obscure how CEP 215 functions for recruitment of the centrosomal proteins
      during the centrosome cycle. Here, we investigated a role of CEP 215 during
      mitosis. Knockdown of CEP 215 resulted in characteristic mitotic phenotypes,
      including monopolar spindle formation, a decrease in distance between the spindle
      pole pair, and detachment of the centrosomes from the spindle poles. We noticed
      that CEP 215 is critical for centrosomal localization of dynein throughout the
      cell cycle. As a consequence, the selective centrosomal proteins were not
      recruited to the centrosome properly. Finally, the centrosomal localization of
      CEP 215 also depends on the dynein-dynactin complex. Based on the results, we
      propose that CEP 215 regulates a dynein-dependent transport of the pericentriolar
      matrix proteins during the centrosome maturation.

PMID- 20139724
TI  - Multiple two-polymerase mechanisms in mammalian translesion DNA synthesis.
AB  - The encounter of replication forks with DNA lesions may lead to fork arrest
      and/or the formation of single-stranded gaps. A major strategy to cope with these
      replication irregularities is translesion DNA synthesis (TLS), in which
      specialized error-prone DNA polymerases bypass the blocking lesions. Recent
      studies suggest that TLS across a particular DNA lesion may involve as many as
      four different TLS polymerases, acting in two-polymerase reactions in which
      insertion by a particular polymerase is followed by extension by another
      polymerase. Insertion determines the accuracy and mutagenic specificity of the
      TLS reaction, and is carried out by one of several polymerases such as poleta,
      polkappa or poliota. In contrast, extension is carried out primarily by polzeta.
      In cells from XPV patients, which are deficient in TLS across cyclobutane
      pyrimidine dimers (CPD) due to a deficiency in poleta, TLS is carried out by at
      least two backup reactions each involving two polymerases: One reaction involves
      polkappa and polzeta, and the other poliota and polzeta. These mechanisms may
      also assist poleta in normal cells under an excessive amount of UV lesions.

PMID- 20139725
TI  - gammaH2AX foci analysis for monitoring DNA double-strand break repair: strengths,
      limitations and optimization.
AB  - DNA double-strand breaks (DSBs) represent an important radiation-induced lesion
      and impaired DSB repair provides the best available correlation with
      radiosensitivity. Physical techniques for monitoring DSB repair require high, non
      physiological doses and cannot reliably detect subtle defects. One outcome from
      extensive research into the DNA damage response is the observation that H2AX, a
      variant form of the histone H2A, undergoes extensive phosphorylation at the DSB,
      creating gammaH2AX foci that can be visualized by immunofluorescence. There is a
      close correlation between gammaH2AX foci and DSB numbers and between the rate of
      foci loss and DSB repair, providing a sensitive assay to monitor DSB repair in
      individual cells using physiological doses. However, gammaH2AX formation can
      occur at single-stranded DNA regions which arise during replication or repair and
      thus does not solely correlate with DSB formation. Here, we present and discuss
      evidence that following exposure to ionizing radiation, gammaH2AX foci analysis
      can provide a sensitive monitor of DSB formation and repair and describe
      techniques to optimize the analysis. We discuss the limitations and benefits of
      the technique, enabling the procedure to be optimally exploited but not misused.

PMID- 20139726
TI  - The many facets of the Tim-Tipin protein families' roles in chromosome biology.
AB  - Failures in DNA replication are a potent force for driving genome instability.
      The proteins which form the replisome, the DNA replication machinery, play a
      fundamental role in preventing replicative catastrophes. The Tim
      (TIMELESS/TIMEOUT) and Tipin proteins are two conserved replisome associated
      proteins which have functions in preventing replication fork collapse and
      replicative checkpoint signalling in response to factors which slow the
      progression of the replisome. Intriguingly, TIMELESS family members have been
      implicated in the regulation of the biological clock, giving a tantalising
      pointer to a possible link between DNA replication and circadian rhythm control.
      Here we report on our current understanding of the many facets of these protein
      families in maintaining genome stability and replication checkpoint control.

PMID- 20139727
TI  - Putting one step before the other: distinct activation pathways for Cdk1 and Cdk2
      bring order to the mammalian cell cycle.
AB  - Eukaryotic cell division is controlled by the activity of cyclin-dependent
      kinases (CDKs). Cdk1 and Cdk2, which function at different stages of the
      mammalian cell cycle, both require cyclin-binding and phosphorylation of the
      activation (T-) loop for full activity, but differ with respect to the order in
      which the two steps occur in vivo. To form stable complexes with either of its
      partners-cyclins A and B-Cdk1 must be phosphorylated on its T-loop, but that
      phosphorylation in turn depends on the presence of cyclin. Cdk2 can follow a
      kinetically distinct path to activation in which T-loop phosphorylation precedes
      cyclin-binding, and thereby out-compete the more abundant Cdk1 for limiting
      amounts of cyclin A. Mathematical modeling suggests this could be a principal
      basis for the temporal ordering of CDK activation during S phase, which may
      dictate the sequence in which replication origins fire. Still to be determined
      are how: (1) the activation machinery discriminates between closely related CDKs,
      and (2) coordination of the cell cycle is affected when this mechanism of pathway
      insulation breaks down.

PMID- 20139728
TI  - Role of endogenous annexin-A1 in the regulation of thymocyte positive and
      negative selection.
AB  - We have recently shown that endogenous Annexin-A1 (AnxA1) plays a homeostatic
      regulatory role in mature T cells by modulating the strength of TCR signaling. In
      this study we investigated the role of endogenous AnxA1 in thymocyte maturation.
      Analysis of AnxA1(-/-) thymocyte populations at the immature CD4(-)CD8(-) double
      negative (DN) stage showed a proportional decrease in the DN1 and an increase in
      the DN3 subsets compared to control littermates. There were no significant
      differences in thymocyte numbers or proportions of CD4(+) and CD8(+) single
      positive (SP) populations between Anx1(-/-) and AnxA1(+/+) mice. However, when we
      crossed AnxA1(-/-) mice onto HY-TCR transgenic mice, we observed an increase in
      CD4(+)CD8(+) double positive (DP) and CD4 SP cells in male AnxA1(-/-)/HY-TCR
      compared to AnxA1(+/+)/HY-TCR. Conversely, female AnxA1(-/-)/HY-TCR mice showed
      an increase in DP and a decrease in CD8 (SP) cells compared to female
      AnxA1(+/+)/HY-TCR. Biochemical analysis of the signaling pathways responsible for
      these effects showed a decrease in anti-CD3-induced Erk phosphorylation and
      NFkappaB activation in AnxA1(-/-) thymocytes compared to control littermates.
      Together these findings demonstrate a role for endogenous AnxA1 in regulating
      both positive and negative selection of the TCR repertoire. These results suggest
      that targeting AnxA1 expression or function in T cells could represent a useful
      approach for the development of novel therapies for the treatment of autoimmune
      diseases.

PMID- 20139729
TI  - Transient increases in p53-responsible gene expression at early stages of Epstein
      Barr virus productive replication.
AB  - Expression of Epstein-Barr Virus BZLF1, a key protein initiating the switch from
      latent to lytic infection, is known to cause cell growth arrest by accumulating
      p53 and p21(WAF1/CIP1) in epithelial cells, but its molecular mechanism remains
      elusive. We found here that the BZLF1 protein stimulates p53 binding to its
      recognition sequence. The BZLF1 accelerated the rate of p53-DNA complex formation
      through the interaction with p53 protein and also enhanced p53-specific
      transcription in vitro. Furthermore, p53 protein was found to bind to its target
      promoter regions specifically in the early stages of lytic replication.
      Overexpression of p53 at the early stages of lytic replication enhanced viral
      genome replication, supporting the idea that p53 plays an important role in the
      initiation steps of EBV replication. Taking the independent role of BZLF1 on p53
      degradation into consideration, we propose that the BZLF1 protein regulates p53
      and its target gene products in two distinctive manners; transient induction of
      p53 at the early stages for the initiation of viral productive replication and
      p53 degradation at the later stages for S-phase like environment preferable for
      viral replication.

PMID- 20139730
TI  - Study of DNA replication in Drosophila using cell free in vitro system.
AB  - Using Drosophila early egg extracts we have developed an optimized cell free
      system to study DNA replication. The efficiency of replication depends on a cold
      treatment of Drosophila embryos before the extract preparation and a formation of
      nuclei facilitated by the addition of membrane fractions to the extracts. In
      vitro DNA replication is ORC and CDC6 dependent, as a removal of these proteins
      from the extracts abolishes DNA replication. The N-terminal part of Orc1 protein,
      which is important for non-replicative functions of ORC, is dispensable for the
      replication in vitro. We also show that the conserved ATP ase motif of CDC6 is
      crucial for the replication. Our studies indicate that a Drosophila cell free
      system proves to be an extremely useful tool for a functional dissection of the
      processes and factors involved in DNA replication in metazoans.

PMID- 20139731
TI  - Upregulation of biosynthetic processes associated with growth by trehalose 6
      phosphate.
AB  - Trehalose 6-phosphate (T6P), the precursor of trehalose, is a signaling molecule
      in plants with strong effects on metabolism, growth and development. We recently
      showed that in growing tissues T6P is an inhibitor of SnRK1 of the SNF1-related
      group of protein kinases. SnRK1 acts as transcriptional integrator in response to
      carbon and energy supply. In microarray experiments on seedlings of transgenic
      Arabidopsis with elevated T6P content we found that expression of SnRK1 marker
      genes was affected in a manner to be predicted by inhibition of SnRK1 by T6P in
      vivo. A large number of genes involved in reactions that utilize carbon, e.g.,
      UDP-glucose dehydrogenase genes involved in cell wall synthesis, were
      upregulated. T6P was also found to affect developmental signaling pathways,
      probably in a SnRK1-independent manner. This includes upregulation of genes
      encoding UDP-glycosyltransferases that are involved in the glycosylation of
      hormones. In addition, genes involved in auxin response and light signaling were
      affected. Many of these genes belong to pathways that link the circadian clock to
      plant growth and development. The overall pattern of changes in gene expression
      supports a role for T6P in coordinating carbon supply with biosynthetic process
      involved in growth and development.

PMID- 20139732
TI  - Signal percolation through plants and the shape of the calcium signature.
AB  - Plants respond to almost any kind of external stimulus with transients in their
      cytoplasmic free calcium concentration ([Ca(2+)](c)). A huge variety of kinetics
      recorded by optical techniques has been reported in the past. This variety has
      been credited the specificity needed to explain how information about incoming
      stimuli is evaluated by the organism and turned into the right physiological
      responses which provide advantages for survival and reproduction. A physiological
      response often takes place away from the site of stimulation. This requires cell
      to-cell communication. Hence, responding cells are not necessarily directly
      stimulated but rather receive an indirect stimulus via cell-to-cell
      communication. It appears unlikely that the '[Ca(2+)](c) signature' in the
      primarily stimulated cell is conveyed over long distances via cell-to-cell
      communication from the 'receptor cells' to the 'effector cells'. Here, a novel
      aspect is highlighted to explain the variety of [Ca(2+)] kinetics seen by
      integrating methods of [Ca(2+)](c) recording. Plants can generally be seen as
      cellular automata with specific morphology and capable for cell-to-cell
      communication. Just a few rules are needed to demonstrate how waves of
      [Ca(2+)](c)-increases percolate through the organism and thereby deliver a broad
      variety of 'signatures'. Modelling intercellular signalling may be a possible way
      to find explanations for different kinds of signal transmission, signal
      amplification, wave formation, oscillations and stimulus-response coupling. The
      basic examples presented here show that care has to be taken when interpreting
      cellular '[Ca(2+)](c) signatures' recorded by optical techniques which integrate
      over a big number of cells or even whole plants.

PMID- 20139733
TI  - Mimicry of molecular pretenders: the terminal structures of satellites associated
      with plant RNA viruses.
AB  - Satellite RNAs (satRNAs) and satellite viruses depend on the replicase complexes
      provided by their cognate helper viruses and host plants for replication,
      pretending that they are part of the viral genomes. Although satRNAs and
      satellite viruses do not share significant nucleotide sequence similarity with
      the helper viruses, the essential cis-acting elements recognized by the replicase
      complexes must reside on their genomes, acting as the mimicry for the molecular
      pretenders. By understanding how this molecular mimicry deceives the helper
      viruses into supporting the satellites, a significant amount of knowledge of the
      basic requirements and mechanisms for replication of viruses and satellites has
      been obtained. Here we review the recent advances in understanding the effects of
      the cis elements at the termini of satRNAs and satellite viruses on their
      accumulation. Several well-characterized satellite/helper virus systems,
      representing the non-coding short satRNAs, mRNA-type long satRNAs, circular
      satRNAs and satellite viruses, are compared and contrasted. It is concluded that
      different satellites may adopt different strategies to exploit the
      replication/transcription/translation machineries of their helper viruses, and
      different mimicries may be implemented by the same molecular pretender for
      different biological functions.

PMID- 20139734
TI  - Transposon defense in Drosophila somatic cells: a model for distinction of self
      and non-self in the genome.
AB  - Genomes need an immune system much like entire organisms, because their integrity
      is threatened by selfish genetic elements which transpose and proliferate at the
      cost of the host. Unlike bacteria or viruses, these DNA parasites do not have any
      particular feature that helps to detect them as foreign sequences within the
      genome-they have no "antigen" so to speak. Nonetheless, sequence-specific defense
      mechanisms have evolved: The germ-line piRNAs rely on previous exposure that has
      left degenerate copies of many transposon-families in certain genomic loci from
      which small RNA sentinels are produced. In addition, the somatic cells of
      Drosophila deploy transposon-complementary endo-siRNAs to repress their activity.
      It was unclear how their precursors are generated or which mechanism leads to
      preferential targeting of transposons. Several publications now report progress
      in our understanding of endo-siRNA biogenesis and propose the first models for
      how "self"-DNA might be distinguished from selfish DNA.

PMID- 20139735
TI  - Understanding the molecular mechanism of transcriptional regulation of banana
      Sucrose phosphate synthase (SPS) gene during fruit ripening: an insight into the
      functions of various cis-acting regulatory elements.
AB  - Recently, we have reported the characterization of promoter region of Sucrose
      phosphate synthase (SPS) gene in banana and investigated the role of some cis
      elements/motifs, present in the promoter of SPS, in the transcriptional
      regulation of the gene. DNA-protein interaction studies have demonstrated the
      presence of specific trans-acting factors which showed specific interactions with
      ethylene, auxin, low temperature and light responsive elements in regulating SPS
      transcription. Transient expression analyses have demonstrated the functional
      significance of the various cis-acting regulatory elements present in banana SPS
      promoter in regulating SPS expression during ripening. (1) Here, we have further
      discussed the possible role of these regulatory sequences in the regulation of
      transcriptional network and comment on their function in relation to sucrose
      metabolism during banana fruit ripening. 

PMID- 20139736
TI  - Helping in food-deceptive orchids? A possible new mechanism maintaining
      polymorphism of floral signals.
AB  - Why different colour morphs have evolved in flowering plants, and how they are
      maintained in populations, have long intrigued ecologists. The impact of
      variation in floral colour and odour (the two are frequently associated) on
      reproductive success remains poorly understood. In European rewardless orchids,
      many species occasionally show rare white-flowered individuals within populations
      of the common-coloured morph. In a recent study, we found that in Orchis mascula
      the presence of rare white-flowered morphs significantly increased the
      reproductive success (from 6% to 27%) of purple-flowered plants, while success of
      the white morph remained low. This surprising result appears due solely to floral
      color polymorphism, which in this species is not associated with odour
      polymorphism. We hypothesize that colour variation plays the key role in
      pollinator attraction, and that white-flowered individuals may be regarded to
      function as "sensory traps". We also propose that the maintenance of white
      flowered mutants in O. mascula may result through kin selection, in which they
      act as helpers increasing the reproductive success of related purple individuals.

PMID- 20139737
TI  - The multifunctionality of dehydrins: an overview.
AB  - Dehydrins are highly hydrophilic proteins that accumulate during embryogenesis
      and water stress responses in plants. Although dehydrins were discovered in the
      1980s, their physiological functions are unknown. However, recent molecular-based
      studies have provided insights into the multifunctionality of dehydrins. The
      functional versatility of dehydrins is reviewed using recent experimental
      evidence, and perspectives in the functional studies of dehydrins are also
      discussed. 

PMID- 20139738
TI  - Plant vaccination: stimulation of defense system by caffeine production in
      planta.
AB  - Plants produce up to 100,000 secondary metabolites. One of their biological
      functions is self-denfese, and it is referred as chemical defense, directly
      and/or indirectly counteracting biotic and abiotic stresses. Alkaloids constitute
      12% of total secondary metabolites, and some of them exhibit detrimental effects
      on living organisms. Caffeine (1,3,7-trimethylxanthine) is a member of purine
      alkaloids, and its exogenous application to plants at relatively high
      concentrations (0.01-0.1%) effectively repelled herbivores and pathogenic
      microbes. This allowed the construction of transgenic crops that endogenously
      produce caffeine to tolerate stresses. Experimentally, tobacco and chrysanthemum
      were successfully transformed with three distinct N-methyltranferases involved in
      the caffeine biosynthesis pathway. They produced 0.4-5 mug caffeine/g tissue (5 x
      10(-4)%), this being three magnitudes lower than values found in caffeine
      producing plants and in vitro experiments. Nevertheless, they exhibited strong
      repellence against pest insects, and high resistance to virus and bacterial
      infection. They also exhibited accelerated self-defense, as estimated by
      constitutive expression of defense-related genes, and by elevated production of
      salicylic acid, a critical signaling molecule for defense response. Since
      caffeine content was low in transgenic lines, observed effects might not be
      direct, but rather indirect. We presume that, as endogenously produced caffeine
      could be toxic, the host plants activated its own self-defense system, which
      commonly occurs regarding other stresses. Eventually the host became on standby
      to cope with a broad range of biotic stresses. The procedure resembles mammalian
      vaccination, in which antigen-antibody system is critical. We propose that plants
      can also be vaccinated as far as proper "antigenic" chemicals are expressed in
      planta. 

PMID- 20139740
TI  - Receptor-like proteins: searching for functions.
AB  - Receptor-like proteins (RLPs) are cell surface receptors, which are composed of
      several distinct domains including a signal peptide, an extracellular leucine
      rich repeat (LRR) region, a transmembrane domain and a short cytoplasmic tail.
      RLPs are implicated in plant growth and development as well as in disease
      resistance. Our previous genome-wide functional analysis of 57 Arabidopsis RLP
      genes (AtRLPs) revealed that mutant phenotypes were only observed for a few genes
      including the two reported genes CLAVATA2 (CLV2) and TOO MANY MOUTHS, despite the
      wide range of growth and developmental stages and treatments that were tested. In
      a recent study, we reported on further insights into the biological role of a few
      AtRLPs closely-related to CLV2. Two AtRLPs (AtRLP2 and AtRLP12), which share high
      sequence similarity with CLV2, were found to be able to rescue the clv2 mutant
      phenotype when expressed under the control of the CLV2 promoter, suggesting that
      the specialization among CLV2, AtRLP2 and AtRLP12 is largely ascribed to
      differences in their expression patterns. Our data further indicated that the
      island domain of CLV2 is dispensable for its function and the C3-F domain of CLV2
      could be replaced by that of AtRLP38. In this Addendum, we are elaborating on
      further strategies concerning the function of largely unknown AtRLPs. 

PMID- 20139739
TI  - A membrane-bound NAC transcription factor as an integrator of biotic and abiotic
      stress signals.
AB  - Transcription factors are central components of gene regulatory networks that
      mediate virtually all aspects of growth and developmental processes in biological
      systems. The activity of transcription factors is regulated at multiple steps,
      such as gene transcription, posttranscriptional RNA processing, posttranslational
      modification, protein-protein interactions, and controlled protein turnover.
      Controlled activation of dormant, membrane-bound transcription factor (MTF) is an
      intriguing regulatory mechanism that ensures quick transcriptional responses to
      environmental fluctuations in plants, in which various stress hormones serve as
      signaling mediators. NTL6 is proteolytically activated upon exposure to cold and
      induces expression of the Pathogenesis-Related (PR) genes. The membrane-mediated
      cold signaling in inducing pathogen resistance is considered to be an adaptive
      strategy that protects plants against infection by hydrophilic pathogens
      frequently occurring during cold season. We found that NTL6 also mediates
      abscisic acid (ABA) regulation of abiotic stress responses in Arabidopsis. NTL6
      is proteolytically activated by ABA. Transgenic plants overexpressing a nuclear
      NTL6 form (35S:6DeltaC) exhibited a hypersensitive response to ABA and high
      salinity in seed germination. Taken together, these observations indicate that
      NTL6 plays an integrative role in plant responses to both biotic and abiotic
      stress conditions. 

PMID- 20139741
TI  - Function of plant defense secondary metabolite in cytokinin degradation.
AB  - The flavoenzyme cytokinin dehydrogenase (CKX) catalyzes an irreversible
      deactivation of plant hormones cytokinins through oxidative cleavage of the
      cytokinin side chain to yield adenine or adenosine and an aldehyde. In the
      catalytic cycle of CKX, the cytokinin-reduced flavin cofactor is reoxidized by a
      suitable electron acceptor. We have recently demonstrated that the oxidation
      products of natural hydroxamic acid 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one
      (DIMBOA) function as effective electron acceptors of apoplastic CKX from maize.
      The stable oxidation product of DIMBOA reacting with peroxidase or laccase was
      identified as 4-nitrosoresorcinol 1-monomethyl ether (coniferron), which,
      however, is only a weak electron acceptor of CKX. Further analyses suggested
      formation of transient free radicals that were estimated to reoxidize the
      cytokinin-reduced flavin cofactor of CKX with the rates comparable to those of
      flavin reduction. 

PMID- 20139742
TI  - Postresection CA 19-9 value as a prognostic factor: in response to the letter by
      Kilickap and Arslan.

PMID- 20139743
TI  - Ureteral stenosis after postprostatectomy intensity-modulated radiotherapy.

PMID- 20139744
TI  - Malignant thymoma with immunodeficiency (Good syndrome) associated with
      mucormycosis.

PMID- 20139750
TI  - Per-contact probability of HIV transmission in homosexual men in Sydney in the
      era of HAART.
AB  - OBJECTIVE: The objective of this study is to estimate per-contact probability of
      HIV transmission in homosexual men due to unprotected anal intercourse (UAI) in
      the era of HAART. DESIGN: Data were collected from a longitudinal cohort study of
      community-based HIV-negative homosexual men in Sydney, Australia. METHODS: A
      total of 1427 participants were recruited from June 2001 to December 2004. They
      were followed up with 6-monthly detailed behavioral interviews and annual testing
      for HIV till June 2007. Data were used in a bootstrapping method, coupled with a
      statistical analysis that optimized a likelihood function for estimating the per
      exposure risks of HIV transmission due to various forms of UAI. RESULTS: During
      the study, 53 HIV seroconversion cases were identified. The estimated per-contact
      probability of HIV transmission for receptive UAI was 1.43% [95% confidence
      interval (CI) 0.48-2.85] if ejaculation occurred inside the rectum, and it was
      0.65% (95% CI 0.15-1.53) if withdrawal prior to ejaculation was involved. The
      estimated transmission rate for insertive UAI in participants who were
      circumcised was 0.11% (95% CI 0.02-0.24), and it was 0.62% (95% CI 0.07-1.68) in
      uncircumcised men. Thus, receptive UAI with ejaculation was found to be
      approximately twice as risky as receptive UAI with withdrawal or insertive UAI
      for uncircumcised men and over 10 times as risky as insertive UAI for circumcised
      men. CONCLUSION: Despite the fact that a high proportion of HIV-infected men are
      on antiretroviral treatment and have undetectable viral load, the per-contact
      probability of HIV transmission due to UAI is similar to estimates reported from
      developed country settings in the pre-HAART era.

PMID- 20139751
TI  - The evolution of protease mutation 76V is associated with protease mutation 46I
      and gag mutation 431V.
AB  - Recently, first-line lopinavir failure was observed due to protease mutation 76V.
      In the present study, we found 76V associated with protease mutation 46I and gag
      cleavage-site mutation 431V. Longitudinal analysis of patients failing protease
      inhibitor therapies demonstrated that 76V strictly occurs either together with
      46I and/or 431V or in HIV isolates already harbouring one of both mutations.
      Therefore, all three mutations seem to cooperate in terms of protease inhibitor
      resistance.

PMID- 20139752
TI  - Effect of tenofovir disoproxil fumarate on risk of renal abnormality in HIV-1
      infected children on antiretroviral therapy: a nested case-control study.
AB  - OBJECTIVE: To investigate the association between tenofovir disoproxil fumarate
      (TDF) use and renal abnormality in a large cohort of HIV-1-infected children on
      antiretroviral therapy (ART). DESIGN: Nested case-control study. METHODS:
      Patients were from the Collaborative HIV Paediatric Study, a cohort of
      approximately 95% of HIV-1-infected children in the UK/Ireland. Serum (but not
      urine) biochemistry results for 2002-2008 were obtained for 456 ART-exposed
      children (2-18 years) seen at seven hospitals. Cases had either confirmed
      hypophosphataemia DAIDS grade at least 2 or estimated glomerular filtration rate
      (eGFR) less than 60 ml/min per 1.73 m; three controls per case were matched by
      hospital. Conditional logistic regression identified risk factors for renal
      abnormality. RESULTS: Twenty of 456 (4.4%) had hypophosphataemia, and one had
      eGFR less than 60 ml/min per 1.73 m. Ten of 20 (50%) cases versus 11 of 60 (18%)
      controls had taken TDF-containing ART for a median [interquartile range (IQR)] of
      18 [17-20] months, as part of second-line or salvage therapy. The
      hypophosphataemia incidence rate was 4.3/100 person-years in the TDF group versus
      0.9/100 person-years in those not exposed to TDF. In multivariable analysis, only
      TDF exposure in the previous 6 months was associated with hypophosphataemia [odds
      ratio (OR) = 4.81, 95% confidence interval (CI) 1.45-16.0, P = 0.01]. In six of
      10 children with hypophosphataemia and at least four subsequent phosphate
      measurements, phosphate values returned to normal when TDF was stopped; in four
      with three measures or less, values rose but remained subnormal. CONCLUSIONS:
      Hypophosphataemia was uncommon (4%), but was associated with prolonged TDF use,
      and was generally reversible following TDF withdrawal. Findings highlight the
      importance of continuing to monitor longer-term renal function, in particular
      tubular function, especially in those taking TDF. Further studies assessing urine
      biochemistry measures which more accurately indicate renal tubular damage are
      required.

PMID- 20139753
TI  - Primary cutaneous PEComa.
AB  - A 48-year-old woman attended a physician because of a solitary cutaneous nodule
      on the left lower leg. Microscopic examination of the excisional specimen
      revealed a dermal tumor composed of nests of epithelioid cells exhibiting clear
      cytoplasm. They had centrally located vesicular nuclei with distinct nucleoli. A
      rich network of capillaries was present throughout. The tumor showed an
      infiltrative border. There was no epidermal involvement. Periodic acid-Shif (PAS)
      and PAS-Diastase stains demonstrated glycogen deposition within the cytoplasm of
      the clear cells. Immunohistochemical evaluation revealed that the tumor cells
      were positive for HMB-45 and microftalmia associated transcription factor (MITF).
      Focal desmin positivity was also seen. The tumor cells were negative for S-100
      protein, alfa smooth muscle actin, HHF-35, and various cytokeratins. The case is
      one of a primary cutaneous pecoma. Pecomas are rare, recently described
      mesenchymal tumors composed of perivascular epithelioid cells. They constitute a
      spectrum of lesions in different organs including angiomyolipoma of the kidney
      and liver, sugar tumor of the lung, lymphangiomatosis, and lymphangiomyoma.
      Primary cutaneous PEComas are exceptionally rare and have only recently been
      recognized. To date, these are approximately 22 cases in the English literature.
      Follow-up data is limited but they appear to behave in a benign fashion. We
      report an additional case with the goal of alerting dermatopathologists to this
      distinctive unusual neoplasm.

PMID- 20139754
TI  - Systematic examination of the dura mater in pediatric pathology.

PMID- 20139755
TI  - Carbon monoxide poisoning from disposable charcoal barbeques.
AB  - Carbon monoxide poisoning is a common cause of accidental death and suicide. This
      article reports 4 cases of carbon monoxide poisoning following the inhalation of
      fumes from disposable charcoal barbeques in a confined space. All of the cases
      occurred within a 2-year period in Northern Ireland. 

PMID- 20139756
TI  - Neurocysticercosis causing sudden death.
AB  - Neurocysticercosis causes significant morbidity due to neurologic manifestations
      including seizures. Sudden unexpected death in epilepsy (SUDEP) is responsible
      for mortality associated with seizure disorders. This case highlights death from
      neurocysticercosis and possible SUDEP in a nonendemic country.

PMID- 20139757
TI  - Preferential expression of MUC6 in oncocytic and pancreatobiliary types of
      intraductal papillary neoplasms highlights a pyloropancreatic pathway, distinct
      from the intestinal pathway, in pancreatic carcinogenesis.
AB  - The expression of different MUC glycoproteins has helped define cellular lineage
      in variety of pancreatic neoplasms, and has helped identify distinct carcinogenic
      pathways such as the intestinal pathway characterized by diffuse/strong MUC2/CDX2
      expression in intestinal-type intraductal papillary mucinous neoplasms (IPMNs)
      and their associated colloid carcinomas (CCs). In this study, the expression
      profile of MUC6, a pyloric-type mucin, was investigated in both preinvasive and
      invasive pancreatic neoplasia. Florid papillary ("in-situ") components of 9
      intraductal oncocytic papillary neoplasms (IOPNs), 24 IPMNs, and 7 mucinous
      cystic neoplasms (MCNs), were analyzed immunohistochemically for MUC6 expression,
      as were 15 PanINs, 112 usual invasive ductal adenocarcinomas (DAs), and 14 CCs.
      In PanINs, MUC6 expression was limited to the very early areas of PanIN-1A that
      typically have pyloric features. Expression was lost in later stages. Similarly,
      in IOPNs or IPMNs or MCNs, MUC6 expression was detectable in the cystic or flat
      areas that have pyloric-like histology. However, in the more advanced (papillary)
      components of these neoplasms, MUC6 expression was mostly limited to the
      "cuboidal-cell" but was not seen in the "columnar-cell" phenotype: there was
      diffuse or strong expression in 8/9 IOPN and, relatively weaker but consistent
      expression in all 6/6 pancreatobiliary-type IPMNs; whereas virtually no
      expression in villous or intestinal-type IPMNs. The 7/8 gastric or foveolar-type
      IPMNs were also negative; in the single case with positivity, the labeling was
      limited to high-grade dysplastic areas. Interestingly, the papillae in MCNs were
      also mostly negative. Among invasive carcinomas, 39/112 DAs and only 1/14 CC
      expressed MUC6. In DA, the expression did not correlate with survival (P=0.94),
      or any of the markers of aggressiveness: more than 2-cm tumor size (P=0.76),
      positive surgical margins (P=0.27), lymph node metastasis (P=0.82), or high grade
      (P=0.08). IN CONCLUSION: (1) The expression of MUC6 in oncocytic and
      pancreatobiliary-type neoplasms but not in villous or intestinal-type neoplasms
      supports the presence of a pyloropancreatic pathway distinct from the MUC2/CDX2
      expressing intestinal pathway in intraductal papillary neoplasia. (2) MUC6
      expression is present in the earliest (nonpapillary) form of any type of
      preinvasive neoplasia regardless of whether it is PanIN or IOPN or IPMN or MCN
      suggesting that these entities may share some characteristics early on, but
      evolve along divergent pathways as they progress.

PMID- 20139758
TI  - Dermatofibrosarcoma protuberans of the vulva: a clinicopathologic and
      immunohistochemical study of 13 cases.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a low-grade sarcoma seldom seen in the
      vulva with only 29 cases reported. We present the clinicopathologic and
      immunohistochemical features of 13 such cases seen in our institution over a
      period of 29 years (1978 to 2007). Patient age ranged from 23 to 76 years (mean,
      46 y). Twelve patients had a vulvar mass. One patient presented with a pigmented
      skin lesion. Tumor size ranged from 1.2 to 15 cm (median, 4 cm). Microscopically,
      all the cases showed typical features of DFSP. In 1 case, myxoid changes were
      also noted; 3 cases showed fibrosarcomatous transformation. Of interest, in 7 of
      our 13 cases, a variety of diagnoses, such as cellular dermatofibroma, cellular
      leiomyoma, neurofibroma, low-grade leiomyosarcoma, fibrosarcoma, low-grade
      malignant schwannoma, desmoplastic melanoma, cellular neurofibroma, and low-grade
      malignant peripheral nerve sheet tumor were initially considered. All 11 cases
      tested for CD34 were positive, whereas 7/9 cases, 8/9 cases, and 9/9 cases were
      positive for PDGFR-alpha, PDGFR-beta, and c-abl, respectively. All patients were
      initially treated with excisional biopsy, wide local excision, or radical
      vulvectomy. Local recurrences occurred in 7 cases. One patient also developed
      distant metastases. All recurrences were treated surgically; 1 patient also
      received chemotherapy and radiotherapy and another received imatinib (Gleevec).
      Follow-up data ranging from 2 to 444 months was available for all patients. Nine
      patients had no evidence of disease, 2 patients were alive with disease, 1
      patient had died of disease, and 1 patient had died of other causes. DFSP affects
      women of a wide age range and has a propensity to recur locally. The frequent
      expression of PDGFR-alpha, PDGFR-beta, and c-abl in these cases agrees with the
      findings of other investigators and supports the use of imatinib (Gleevec) in
      cases that are recurrent or not amenable to surgery.

PMID- 20139759
TI  - Lipid-rich and clear cell neuroendocrine tumors ("carcinoids") of the appendix:
      potential confusion with goblet cell carcinoid.
AB  - The so-called clear cell change has been described in neuroendocrine tumors at
      several locations. Those associated with von Hippel Lindau disease are
      pathognomonically "clear" and the cytoplasmic appearance has been ascribed to
      intracytoplasmic lipid. However, lipid has not been demonstrated in all cases of
      clear cell carcinoid tumors. Such variants have not been described in carcinoid
      tumors of the appendix and cases with a prominent proportion of clear or more
      correctly, lipid-rich cytoplasm may bear a superficial resemblance to goblet cell
      carcinoid and/or signet ring adenocarcinoma. Seven cases, in 5 females and 2
      males ranging in age from 22 to 65 years, were noted to have a population of
      lipid-rich and vacuolated clear cells accounting for 25% or more of the tumor
      population. The carcinoid tumors were incidental in all cases with 4 of patients
      presenting with appendicitis, 2 with concomitant mucinous cystadenocarcinomas of
      the appendix and 1 with an adenocarcinoma of the ascending colon.
      Morphologically, the tumors had a nested and trabecular pattern and were composed
      of an admixture of microvesicular and clear lipid-rich cells. There were no
      mitoses, areas of necrosis of lymphovascular invasion and all cases extended to
      the mesoappendix. All cases were positive for synaptophysin, chromogranin, and
      serotonin but negative for inhibin. Three cases were examined ultrastructurally,
      and showed the presence of intracytoplasmic lipid and neurosecretory granules.
      None of the patients have shown evidence of recurrent disease. The importance of
      recognizing this variant of carcinoid tumor in the appendix is to avoid confusion
      with goblet cell carcinoid tumors with or without a signet ring adenocarcinoma.
      The presence of multi-vacuolated, foamy and clear cells, some resembling signet
      ring or goblet cells, in otherwise classic carcinoid tumors is rare but should be
      considered in this context in the appendix.

PMID- 20139760
TI  - Epstein-Barr virus-associated diffuse large B-cell lymphoma arising on cardiac
      prostheses.
AB  - Primary cardiac lymphoma is extremely rare and lymphoma arising in association
      with prosthetic valves has been described in only 3 case reports. We describe 3
      patients with diffuse large B-cell lymphoma (DLBCL) involving prosthetic heart
      valves and a synthetic tube graft. All 3 specimens showed shallow layering of
      acellular fibrinous debris over the prosthetic or synthetic materials, with tumor
      lymphocytes present at the luminal surface. There were frequent mitoses and
      abundant karyorrhectic debris. All demonstrated a nongerminal center B-cell
      phenotype. All 3 cases were positive for Epstein-Barr virus, but there was no
      staining for human herpes virus 8. There was no other evidence of distant disease
      at the time of diagnosis and no recurrence or dissemination occurred after
      surgical removal of the prosthesis, though follow-up was limited. On the basis of
      2008 World Health Organization diagnostic criteria, we believe these cases should
      be classified as DLBCL associated with chronic inflammation. However, unlike the
      characteristically poor prognosis reported in this entity, we hypothesize that
      the disease resectability in these cardiac sites, in many cases, may allow for a
      better prognosis than DLBCL with chronic inflammation at other less resectable
      sites.

PMID- 20139761
TI  - Distinctive association of p16INK4a overexpression with penile intraepithelial
      neoplasia depicting warty and/or basaloid features: a study of 141 cases
      evaluating a new nomenclature.
AB  - From the pathogenic point of view, penile cancers may be grouped in human
      papillomavirus-related and unrelated tumors, each one of them with distinctive
      morphologic features. The former are predominantly composed of small,
      undifferentiated basaloid cells, with more or less prominent koilocytic changes,
      and the latter of keratinizing differentiated squamous cells. The same cellular
      types are observed in precancerous lesions. On the basis of these observations,
      we constructed a novel nomenclature for penile precancerous lesions and
      classified them as penile intraepithelial neoplasia (PeIN) of differentiated,
      warty, basaloid, and warty-basaloid types. The aim of this study was to test the
      usefulness of immunohistochemical p16 overexpression, considered as a surrogate
      for high-risk human papillomavirus infection, using this classification system.
      We pathologically evaluated 141 patients with PeIN, associated (123 cases) and
      unassociated (18 cases) with invasive cancer. Distribution of PeIN types was:
      differentiated, 72%; basaloid, 9%; warty-basaloid, 7%; warty, 4%; and mixed, 7%.
      There was a striking similarity in the morphology of in situ and invasive
      squamous cell carcinomas. Differentiated PeIN was commonly associated with usual,
      verrucous, papillary, and other low-grade keratinizing variants of squamous cell
      carcinoma whereas in basaloid and warty carcinomas the presence of in situ
      lesions with similar morphology was habitual. We evaluated p16 overexpression
      using a 4-tiered (0, 1, 2, and 3) pattern-based system. To properly distinguish
      differentiated PeIN from in situ lesions with warty and/or basaloid features only
      pattern 3, which requires full-thickness staining in all epithelial cells, was
      considered positive. Using this approach, there was a significant association of
      the negative patterns and differentiated PeIN and of the positive pattern and
      warty, basaloid, and warty-basaloid PeIN (P<0.0001). Basaloid variant had the
      strongest association. The sensitivity rate of p16 positivity for discriminating
      types of PeIN was of 82%, with a specificity of 100% and an accuracy of 95%.
      Lichen sclerosus was identified in 42 cases and their epithelial component was
      p16 negative in all cases. Although more studies are necessary to confirm these
      observations, p16 overexpression seems to be a useful tool for discriminating
      differentiated from warty, basaloid, and warty-basaloid PeIN.

PMID- 20139762
TI  - Urothelial carcinoma of the bladder, lipid cell variant: clinicopathologic
      findings and LOH analysis.
AB  - In this report, we present the clinicopathologic features of 27 cases of the
      lipid cell variant of urothelial bladder carcinoma. This is a rare variant of
      bladder cancer recognized by the current WHO classification of urologic tumors.
      The lipid cell component varied from 10% to 50% of the tumor specimen; in 11
      cases the lipid cell component composed greater than 30% of the tumor. The
      architectural pattern of the tumor varied from solid expansile to infiltrative
      nests. The large epithelial tumor cells had an eccentrically placed nucleus and
      abundant vacuolated cytoplasm resembling signetring lipoblasts. Mucin stains were
      negative in all the cases. Typical features of high grade conventional urothelial
      carcinoma were present in all the cases with micropapillary or plasmacytoid
      carcinoma in 2 and 1 cases, respectively; extensive squamous or glandular
      differentiation was present in 2 additional cases. Most neoplastic cells had
      nuclei of intermediate nuclear grade with occasional nuclear pleomorphism.
      Immunohistochemical staining showed that the lipid cell component was positive
      for cytokeratins 7, 20, CAM 5.2, high molecular weight (34ssE12) and AE1/AE3,
      epithelial membrane antigen, and thrombomodulin; vimentin and S100 protein were
      negative. The loss of heterozygosity (LOH) analysis was done on 8 cases using 4
      polymorphic microsatellite markers (D9S171, D9S177, IFNA, and TP 53); LOH at
      least in 1 marker was present in 6 cases. The LOH results were the same for lipid
      variant and conventional urothelial carcinoma. Pathologic stage was Ta (n=1), T1
      (=2), T2, at least (n=7), T3a (n=4), T3b (n=8), and T4a (n=5). Electron microcopy
      analysis based on 2 cases supported lipid content in tumor cells. Follow-up
      information was available in all the cases, ranging from 6 to 58 months (mean, 28
      mo). Sixteen of the patients died of disease at 16 to 58 months (mean, 33 mo) and
      8 patients were alive with disease at 8 to 25 months (mean, 22 mo). Another 3
      patients died of other causes at 6 to 15 months (mean, 10 mo). In summary, lipid
      cell urothelial bladder carcinoma is typically associated with advanced stage
      high-grade urothelial carcinoma, in which the prognosis is poor and clonally
      related to the concurrent conventional urothelial carcinoma. In limited samples,
      it may be misdiagnosed as liposarcoma, sarcomatoid carcinoma (carcinosarcoma), or
      signetring cell carcinoma. Morphologic distinction from other malignant neoplasms
      with lipid cell phenotype is critical for its clinical management.

PMID- 20139763
TI  - Screening and treating asymptomatic bacteriuria in pregnancy.
AB  - PURPOSE OF REVIEW: Asymptomatic bacteriuria (ASB) in pregnancy, if left
      undiagnosed and appropriately treated can lead to acute pyelonephritis in mothers
      and low birth weight in infants. Urine culture is the gold standard for
      diagnosing ASB. Unfortunately, urine culture is limitedly available. The present
      review aims at evaluating performance of various screening tests and
      effectiveness of antibiotic regimens for ASB. RECENT FINDINGS: Positive dipslide
      test is very likely to have a definitive diagnosis of ASB, whereas a negative
      result effectively rules out ASB. Available evidences regarding the performance
      of urine dipstick are still conflicting, it is currently not appropriate to
      recommend urine dipstick for screening ASB in pregnancy. Choice of antibiotics
      should be guided by antimicrobial susceptibility testing whenever possible.
      Nitrofurantoin seems to be antibiotic of choice for ASB in pregnancy. Seven-day
      regimen of antibiotics gives a better microbiological cure rate but no difference
      in important clinical outcomes compared with 1-day regimen. SUMMARY: Dipslide
      culture is a promising screening test for ASB. Pregnant women with ASB should be
      treated with 7-day regimen of antibiotics, although 1-day regimen might be
      appropriate in some settings. More research is needed for identifying appropriate
      screening tests for ASB.

PMID- 20139764
TI  - The clinical use of inflammatory markers during pregnancy.
AB  - PURPOSE OF REVIEW: There is overwhelming evidence that intrauterine infection and
      inflammation play an important role in the pathogenesis of spontaneous preterm
      labor, preterm prelabor rupture of the membranes and fetal injury resulting in
      long-term sequelae. Early diagnosis of subclinical infection and inflammation may
      therefore aid clinicians institute interventions focusing on such adverse
      outcomes. RECENT FINDINGS: Biomarkers of intrauterine inflammation such as
      interleukin-6, although sensitive, are not specific. Thus, decision to deliver
      remote from term because of intrauterine infection and/or inflammation should be
      based on clinical signs and/or bacterial culture or Gram stain of amniotic fluid.
      In patients with preterm contractions and intact membranes, the risk of delivery
      is 1% within the week following a negative fetal fibronectin in cervicovaginal
      secretions. This aids to decide whether antenatal steroids should be administered
      to patients presenting with preterm contractions between 24 and 34 weeks'
      gestation. Biomarkers in cervical secretions and amniotic fluid identify those
      who may benefit from cerclage when the cervix is shortened (<25 mm) and dilated
      in the second trimester. SUMMARY: So far, few interventions utilizing
      inflammatory biomarkers have shown clinical benefit. Future efforts should focus
      on the quest for accurate biomarkers that can be obtained noninvasively and allow
      early prediction of subclinical disease to initiate appropriate risk-specific
      intervention.

PMID- 20139765
TI  - Fetal transfusion: the spectrum of clinical research in the past year.
AB  - PURPOSE OF REVIEW: Our goal is to review recent articles that examine the current
      state of fetal transfusion therapy from technique to education. RECENT FINDINGS:
      Even as technology facilitates physicians' diagnosis and treatment of rare
      disorders requiring fetal transfusion therapy, longstanding questions remain such
      as the use of intravascular versus intraperitoneal transfusion sites. However,
      the recent progress seen with molecular techniques, disease markers, and
      mathematical models demonstrates that despite unanswered questions, there is much
      to be hopeful about in improving our understanding of fetal transfusions and
      their application to a variety of diseases. SUMMARY: Systematic and collaborative
      approaches to studying low-frequency disorders treatable by fetal transfusions
      are necessary. Continued refinement of techniques should improve the timeliness
      and accuracy of diagnosis, as well as assist in determining the appropriate
      timing, site, and duration of treatments.

PMID- 20139766
TI  - Newborn screening--the unique role of unique evidence.

PMID- 20139768
TI  - Working alliance and vocational outcomes for cancer survivors: an initial
      analysis.
AB  - This study examines the sex differences in the perception of working alliance and
      the perceptions of optimism regarding future employment and job satisfaction with
      adult cancer survivors receiving vocational rehabilitation services. No
      significant differences were found between males and females in terms of the
      three components of the working alliance. However, examination of effect sizes
      indicated that the females reported higher levels of tasks (d=0.40) and goals
      (d=0.55) than their male counterparts. The three components of working alliance
      explained 60% of the variance with bonds (beta=0.865) making a significant and
      unique contribution to employment prospects. Working alliance was not associated
      with current job satisfaction in the employed group. Overall results of this
      study suggest that working alliance seems to be an important variable in the
      vocational outcomes for cancer survivors receiving vocational services.

PMID- 20139769
TI  - Office and 24-h ambulatory blood pressure control by treatment in general
      practice: the 'Monitoraggio della pressione ARteriosa nella medicina
      TErritoriale' study.
AB  - BACKGROUND: Guidelines recommend that blood pressure (BP) should be lowered in
      hypertensive patients to prevent cardiovascular accidents. Management of
      antihypertensive treatment by general practitioners is usually based on office
      measurements, which may not allow an assessment of BP control over 24 h, which
      requires ambulatory BP monitoring (ABPM) to be implemented. This is rarely done
      in general practice, and limited information is available on the consistency
      between the evaluations of the response to treatment provided by office
      measurement and by ABPM in this setting. AIM: To assess concordance between
      office BP measurements and ABPM-based estimates of hypertension control in a
      general practice setting. DESIGN OF STUDY: Prospective, comparative between
      techniques. SETTING: General practice. METHODS: Seventy-eight general practices,
      representative of all Italian regions, participated in this study by recruiting
      sequential hypertensive adults on stabilized treatment, who were subdivided into
      even groups with office BP, respectively, controlled or noncontrolled by
      treatment. In each individual, ABPM was applied by the general practitioner after
      appropriate training, and 24-h ABP values were defined as controlled or not
      according to current guidelines. Concordance between office and ABPM evaluation
      of BP control was assessed with kappa statistics. Positive and negative
      predictive values of office measurement versus ABPM were estimated. RESULTS:
      Between July 2005 and November 2006, 190 general practitioners recruited 2059
      hypertensive patients based on office BP measurements; in 1728 patients, a 24-h
      ABPM was performed, yielding 1524 recordings considered as valid for further
      analysis. The agreement between the assessment of BP control by office
      measurement and by ABPM was poor (kappa = 0.120), with office measurements
      showing a satisfactory positive predictive value (0.842) and a poor negative
      predictive value (0.278); the situation was worse in patients with three or more
      among the following features: male sex, age of at least 65 years, alcohol
      consumption, diabetes, and obesity (negative predictive value = 0.149).
      CONCLUSION: In general practice, the agreement between assessment of BP control
      by treatment provided by office and ambulatory BP measurements is better in
      patients of 'uncontrolled' office BP than in 'controlled' office BP patients.
      This emphasizes the need for the larger use of out-of-office BP monitoring in a
      general practice setting, in particular, in patients considered as 'controlled'
      during consultation.

PMID- 20139767
TI  - "I know what you told me, but this is what I think:" perceived risk of Alzheimer
      disease among individuals who accurately recall their genetics-based risk
      estimate.
AB  - PURPOSE: This study evaluates the Alzheimer disease risk perceptions of
      individuals who accurately recall their genetics-based Alzheimer disease risk
      assessment. METHODS: Two hundred forty-six unaffected first-degree relatives of
      patients with Alzheimer disease were enrolled in a multisite randomized
      controlled trial examining the effects of communicating APOE genotype and
      lifetime Alzheimer disease risk information. RESULTS: Among the 158 participants
      who accurately recalled their Alzheimer disease risk assessment 6 weeks after
      risk disclosure, 75 (47.5%) believed their Alzheimer disease risk was more than
      5% points different from the Alzheimer disease risk estimate they were given.
      Within this subgroup, 69.3% believed that their Alzheimer disease risk was higher
      than what they were told (discordant high), whereas 30.7% believed that their
      Alzheimer disease risk was lower (discordant low). Participants with a higher
      baseline risk perception were more likely to have a discordant-high risk
      perception (P < 0.05). Participants in the discordant-low group were more likely
      to be APOE epsilon4 positive (P < 0.05) and to score higher on an Alzheimer
      disease controllability scale (P < 0.05). CONCLUSION: Our results indicate that
      even among individuals who accurately recall their Alzheimer disease risk
      assessment, many people do not take communicated risk estimates at face value.
      Further exploration of this clinically relevant response to risk information is
      warranted.

PMID- 20139770
TI  - Stimulating autoantibodies against the angiotensin II type 1 receptor are not
      associated with preeclampsia in Mexican-Mestizo women.
AB  - OBJECTIVE: Recent studies have demonstrated that stimulating autoantibodies
      against the angiotensin II type 1 receptor (AT1R-AA) are frequently detected in
      the sera from women with preeclampsia, suggesting that they may play an important
      role in the pathogenesis of this disease. Nevertheless, the real clinical
      significance of AT1R-AA in preeclampsia is still controversial due to the paucity
      of appropriate large comparative studies that require cumbersome, time-consuming,
      and expensive bioassays to detect AT1R-AA. At present, the prevalence of AT1R-AA
      in large populations of preeclamptic women is unknown. In an attempt to clarify
      this issue, we assessed the presence and potential clinical significance of AT1R
      AA in a large population of Mexican-Mestizo women with preeclampsia. METHODS:
      Using a cross-sectional design, we determined the presence of AT1R-AA in 525
      pregnant women (99 healthy pregnant, 96 with mild preeclampsia, and 330 with
      severe preeclampsia) by a new bioassay that employs human embryonic kidney-293
      cells stably expressing the recombinant rat AT1R and a 4x nuclear factor of
      activated T cells responsive luciferase construct as well as by the reference
      assay in Chinese hamster ovary (CHO) cells. RESULTS: We found that IgG obtained
      from sera of healthy pregnant women and patients with preeclampsia were unable to
      induce luciferase activity in both HEK-293 and Chinese hamster ovary cells
      expressing functional angiotensin II receptor type 1. Therefore, the frequency of
      patients with AT1R-AA was zero. CONCLUSION: We concluded that in Mexican-Mestizo
      women agonistic AT1R-AA cannot be invoked as a factor involved in the
      pathogenesis of preeclampsia. Whether these findings can be attributed to genetic
      or environmental factors remains unknown.

PMID- 20139772
TI  - Association between the sympathetic firing pattern and anxiety level in patients
      with the metabolic syndrome and elevated blood pressure.
AB  - OBJECTIVE: Recent evidence indicates that stress is associated with obesity,
      hypertension and metabolic abnormalities. Stress pathways, including both the
      hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, are
      activated in individuals with the metabolic syndrome. In order to gain some
      insight into the relation between sympathetic nervous system activation,
      metabolic profile and stress, we examined the pattern of sympathetic nervous
      firing in eight women and 17 men with the metabolic syndrome and elevated blood
      pressure (BP) in relation to their underlying psychological stress. METHODS AND
      RESULTS: Both multiunit and single-unit muscle sympathetic nerve activity (MSNA)
      were recorded by using the technique of microneurography and psychological stress
      was assessed by Spielberger's State and Trait Anxiety scores and the Beck
      Depression Inventory II (BDI-II). Women had higher cholesterol levels, higher
      depressive symptom scores and similar multiunit MSNA compared with the men but
      displayed a disturbed firing pattern of sympathetic activity as indicated by a
      higher incidence of multiple spikes per burst (P < 0.05). In all individuals,
      regression analysis after adjustment for sex indicated that the single-unit
      sympathetic nerve-firing pattern did not correlate with any aspect of the
      metabolic profile; however it was significantly associated with anxiety state and
      trait and the affective component of the BDI scores. In particular, higher
      incidence of multiple firing (more than two spikes) during a sympathetic neural
      burst was associated with higher trait anxiety score (R = 0.557, P = 0.004) and
      higher affective depressive symptoms (R = 0.517, P = 0.008). Somatic symptoms
      bore no association with the sympathetic firing pattern. CONCLUSION: These
      results suggest that chronic mental stress modulates the pattern of sympathetic
      activity, which, in turn, may confer greater cardiovascular risk on individuals
      with the metabolic syndrome and elevated BP.

PMID- 20139771
TI  - Effects of chromogranin A deficiency and excess in vivo: biphasic blood pressure
      and catecholamine responses.
AB  - OBJECTIVE: The phenotype of the chromogranin A (Chga) null (knockout) mouse is
      hypertensive. However, hypertensive humans and spontaneously hypertensive rats
      display elevated CHGA expression. This study addresses the paradox that both
      ablation and elevation of CHGA result in hypertension. METHODS: Mice with varying
      copy number of the CHGA gene were generated. In these mice CHGA, catecholamine
      and blood pressure (BP) were measured. Also a cohort of healthy human individuals
      was stratified into tertiles based on plasma CHGA expression and phenotyped for
      characteristics including their BP response to environmental (cold) stress.
      RESULTS: The mice displayed a direct CHGA gene dose-dependent (0-4 copies/genome)
      activation of CHGA expression in both plasma and adrenal gland, yet the BP
      dependence of CHGA gene dose was U-shaped, maximal at 0 and four copies of the
      gene, whereas minimal at two copies (i.e., the wild-type gene dosage). Plasma
      catecholamine showed a parallel U-shaped dose/response in mice, whereas adrenal
      epinephrine exhibited a reciprocal (inverted) U-shaped response, suggesting
      dysregulated neurotransmission at both extremes of CHGA expression. The human
      individuals also showed a nonlinear relationship between CHGA expression and
      pressor responses to environmental (cold) stress, that were maximal in the
      highest and lowest tertiles, though basal BPs did not differ among the groups.
      The human CHGA tertiles also differed in epinephrine secretion as well as degree
      of CHGA processing to catestatin (catecholamine release-inhibitory peptide
      derived from CHGA processing). CONCLUSION: Thus, across mammalian species, an
      optimal amount of CHGA may be required to establish appropriate catecholamine
      storage and release, and hence BP homeostasis.

PMID- 20139773
TI  - Soluble iC3b as an early marker for pancreatic adenocarcinoma is superior to
      CA19.9 and radiology.
AB  - Pancreatic adenocarcinoma as an aggressive tumor still lacks specific markers.
      Resection offers the only potential cure, and earlier diagnosis could benefit
      many patients. Here, we analyzed siC3b as a potential diagnostic marker. Soluble
      iC3b is generated in the fluid phase after binding of autoantibodies to tumor
      cells and subsequent inactivation of the complement cascade by interaction with
      complement regulatory proteins. Two hundred thirty-two plasma samples from
      patients with adjuvant treatment after resection, from healthy volunteers, and
      from vulnerable patients were collected prospectively and analyzed for siC3b.
      Every 3 months, the patients underwent imaging and the results from siC3b enzyme
      linked immunosorbent assay were categorized according to radiologically defined
      recurrence within 4 months after blood withdrawal. Furthermore, the regulatory
      factors of the complement system were analyzed in tumor cells and in urine. The
      most important finding was that up to 4 months before radiologically defined
      recurrence, siC3b plasma level is increased with a sensitivity and specificity
      resulting in an area under the curve of 0.85, which could be further increased by
      combining it with CA19.9 (area under the curve=0.92). Complement regulatory
      proteins are highly expressed in pancreatic carcinoma cells and detectable in the
      patient's urine. In summary, screening for siC3b in patients with an increased
      risk for pancreatic ductal adenocarcinoma (patients with chronic pancreatitis,
      hereditary pancreatitis, after curative resection, and patients with a variety of
      familial cancer syndromes) allows for early detection with high sensitivity, as
      siC3b plasma levels are increased up to 4 months before radiologic evidence.
      Sensitivity could be further increased by combining this approach with CA19.9.

PMID- 20139774
TI  - Low-dose cyclophosphamide treatment impairs regulatory T cells and unmasks AFP
      specific CD4+ T-cell responses in patients with advanced HCC.
AB  - Immunotherapy represents a potential therapeutic option for patients with
      hepatocellular carcinoma (HCC). However, CD4CD25Foxp regulatory T cells, which
      suppress potential antigen-specific T-cell responses, are increased in patients
      with HCC and might impair the effect of an immune-based therapeutic approach. In
      this study, we demonstrate that depletion of regulatory T cells in vitro unmasks
      alpha-fetoprotein-specific T-cell responses in HCC patients. On the basis of
      these results, we performed a clinical trial, in which 13 patients with advanced
      HCC ineligible for any other type of treatment were treated with 150, 250, or 350
      mg/m cyclophosphamide on day 1 and 29 to suppress regulatory T cells in these
      patients (NCT00396682). The primary end point of this trial was regulatory T-cell
      number and function. Low-dose cyclophosphamide treatment (150 and 250 mg/m)
      induced a decrease in the absolute and relative frequency of CD4CD25Foxp
      regulatory T cells in peripheral blood on days 8 and 29. Suppressor function of
      regulatory T cells was impaired after treatment of patients with 250 mg/m on days
      8 and 21. Finally, alpha-fetoprotein-specific T-cell responses were unmasked in
      6/13 treated patients. In summary, systemic treatment of HCC patients with low
      dose cyclophosphamide decreases the frequency and suppressor function of
      circulating CD4CD25Foxp regulatory T cells in peripheral blood and could be used
      in combination with immunotherapeutic approaches in HCC.

PMID- 20139775
TI  - Dendritic cells (DCs) can be successfully generated from leukemic blasts in
      individual patients with AML or MDS: an evaluation of different methods.
AB  - Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived
      dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen
      repertoire without knowledge of distinct leukemia antigens and are regarded as
      promising candidates for a vaccination strategy. We studied the capability of 6
      serum-free DC culture methods, chosen according to different mechanisms, to
      induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating
      substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"),
      bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine
      bypass method ("Ca-ionophore"). The quality/quantity of DC generated was
      estimated by flow cytometry studying (co) expressions of "DC"antigens,
      costimulatory, maturation, and blast-antigens. Comparing these methods on average
      15% to 32% DC, depending on methods used, could be obtained from blast-containing
      mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In
      all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be
      converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%).
      Average results of all culture methods tested were comparable, however not every
      given case of AML could be differentiated to DC with 1 selected method. However
      performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca
      ionophore) we could generate DC in any given case. Functional analyses provided
      proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although
      an anti-leukemic reaction was not achieved in every case. In summary our data
      show that a successful, quantitative DC/DCleu generation is possible with the
      best of 3 previously tested methods in any given case. Reasons for different
      functional behaviors of DC-primed T cells must be evaluated to design a
      practicable DC-based vaccination strategy.

PMID- 20139776
TI  - TAR1, a human anti-p53 single-chain antibody, restores tumor suppressor function
      to mutant p53 variants.
AB  - The tumor suppressor gene p53 is mutated in more than half of human tumors. One
      important characteristic of p53 mutants is their accumulation in the nucleus of
      cancer cells. Thus, reactivation of mutant p53 proteins may trigger massive
      apoptosis in tumor cells. Pharmacologic methods are currently under development
      to induce mutant p53 proteins to resume their wild-type function. We have
      identified a human single-chain Fv fragment, designated as transcriptional
      transactivation and apoptosis restoring (TAR1), which specifically and with high
      affinity binds to mutant p53 and restores its wild-type active conformation.
      Binding of TAR1 to mutant p53 induced transcriptional transactivation of p53
      target genes and down-regulation of mutant p53 transcriptional target genes. TAR1
      treatment induced apoptosis in a variety of cell lines endogenously expressing
      p53 carrying different point mutations DNA contact or structural p53 mutants.
      Moreover, in an animal model of mice carrying human xenografts, TAR1 induced
      tumor regression with no apparent deleterious side effects. Thus, it may be
      considered as a potential candidate for anticancer treatment, targeting tumors
      with mutant p53.

PMID- 20139777
TI  - 25-on-25: twenty-five perspectives on twenty-five years of cardiopulmonary
      imaging.

PMID- 20139778
TI  - A pessimistic explanatory style is prognostic for poor lung cancer survival.
AB  - BACKGROUND: Several studies have demonstrated the importance of personality
      constructs on health behaviors and health status. Having a pessimistic outlook
      has been related to negative health behaviors and higher mortality. However, the
      construct has not been well explored in cancer populations. METHODS: Survival
      time of 534 adults who were diagnosed with lung cancer was examined. The patients
      had completed the Minnesota Multiphasic Personality Inventory approximately 18.2
      years before receiving their lung cancer diagnosis. Minnesota Multiphasic
      Personality Inventory Optimism-Pessimism scores were divided into high (60 or
      more) and low scores (<60), and log-rank tests and Kaplan-Meier curves were used
      to determine survival differences. Multivariate Cox models were used for
      assessing prognostic values of pessimism along with other known predictors for
      lung cancer survival outcome. Bootstrapping of the survival models was used as a
      sensitivity analysis. RESULTS: At the time of lung cancer diagnosis, patients
      were at an average age of 67 years old; 48% of them were women, 85% had non-small
      cell lung cancer, 15% had small cell lung cancer, 30% were stage I, 4% were stage
      II, 31% were stage III/limited, and 35% were stage IV/extensive. Patients who
      exhibited a nonpessimistic explanatory style survived approximately 6 months
      longer than patients classified as having a pessimistic explanatory style.
      CONCLUSION: Among lung cancer patients, those having a pessimistic explanatory
      style experienced a less favorable survival outcome, which may be related to
      cancer treatment decisions. Further research in this area is warranted.

PMID- 20139779
TI  - Effect of infraction type on head impact severity in youth ice hockey.
AB  - PURPOSE: To identify the effects of infractions sustained during participation in
      youth ice hockey on biomechanical measures of head impact severity. METHODS:
      Sixteen adolescent Bantam-aged male ice hockey players (age = 14.0 +/- 0.5 yr,
      height = 171.3 +/- 4.5 cm, mass = 63.7 +/- 6.6 kg) were equipped with
      accelerometer-instrumented helmets to collect biomechanical measures relating to
      head impacts (linear acceleration, rotational acceleration, and Head Impact
      Technology severity profile (HITsp)) sustained while participating in ice hockey.
      Single-camera video footage from 54 games was synchronized with the head impact
      data, and all viewable collisions (n = 665) were evaluated as resulting from a
      legal collision or an infraction. Infractions were further categorized into
      boarding or charging, checking from behind, and elbowing or intentional head
      contact. Statistical analyses included random-intercepts general linear mixed
      models. RESULTS: Infractions were observed in 17.3% (115/665) of all body
      collisions. Overall, collisions involving infractions had higher linear
      accelerations (P = 0.012) and HITsp (P = 0.021) than collisions with no
      infraction. Specifically, elbowing, head contact, and high sticking infractions
      resulted in greater linear acceleration (P = 0.005) and HITsp (P = 0.010) than
      collisions with no infraction. A strong trend for higher rotational accelerations
      in this infraction type compared with legal collisions was also present (P =
      0.059). CONCLUSIONS: Infractions result in higher measures of head impact
      severity than noninfraction collisions. Athletes and coaches should conform to
      playing rules, and officials should enforce more stringently existing rules and
      assess more severe penalties to participants who purposefully attempt to foul an
      opponent at the youth ice hockey level.

PMID- 20139780
TI  - Adaptations in athletic performance after ballistic power versus strength
      training.
AB  - PURPOSE: To determine whether the magnitude of improvement in athletic
      performance and the mechanisms driving these adaptations differ in relatively
      weak individuals exposed to either ballistic power training or heavy strength
      training. METHODS: Relatively weak men (n = 24) who could perform the back squat
      with proficient technique were randomized into three groups: strength training (n
      = 8; ST), power training (n = 8; PT), or control (n = 8). Training involved three
      sessions per week for 10 wk in which subjects performed back squats with 75%-90%
      of one-repetition maximum (1RM; ST) or maximal-effort jump squats with 0%-30% 1RM
      (PT). Jump and sprint performances were assessed as well as measures of the force
      velocity relationship, jumping mechanics, muscle architecture, and neural drive.
      RESULTS: Both experimental groups showed significant (P < or = 0.05) improvements
      in jump and sprint performances after training with no significant between-group
      differences evident in either jump (peak power: ST = 17.7% +/- 9.3%, PT = 17.6%
      +/- 4.5%) or sprint performance (40-m sprint: ST = 2.2% +/- 1.9%, PT = 3.6% +/-
      2.3%). ST also displayed a significant increase in maximal strength that was
      significantly greater than the PT group (squat 1RM: ST = 31.2% +/- 11.3%, PT =
      4.5% +/- 7.1%). The mechanisms driving these improvements included significant (P
      < or = 0.05) changes in the force-velocity relationship, jump mechanics, muscle
      architecture, and neural activation that showed a degree of specificity to the
      different training stimuli. CONCLUSIONS: Improvements in athletic performance
      were similar in relatively weak individuals exposed to either ballistic power
      training or heavy strength training for 10 wk. These performance improvements
      were mediated through neuromuscular adaptations specific to the training
      stimulus. The ability of strength training to render similar short-term
      improvements in athletic performance as ballistic power training, coupled with
      the potential long-term benefits of improved maximal strength, makes strength
      training a more effective training modality for relatively weak individuals.

PMID- 20139781
TI  - Palm cooling delays fatigue during high-intensity bench press exercise.
AB  - Local cooling can induce an ergogenic effect during a short-term intense
      exercise. One proposed method of personal cooling involves heat extraction from
      the palm. PURPOSE: In this study, we hypothesized that local palm cooling (PC)
      during rest intervals between progressive weight training sets will increase
      total repetitions and exercise volume in resistance-trained subjects exercising
      in a thermoneutral (TN) environment. METHODS: Sixteen male subjects (mean +/- SD;
      age = 26 +/- 6 yr, height = 178 +/- 7 cm, body mass = 81.5 +/- 11.3 kg, one
      repetition maximum (1RM) bench press = 123.5 +/- 12.6 kg, weight training
      experience = 10 +/- 6 yr) performed four sets of 85% 1RM bench press exercise to
      fatigue, with 3-min rest intervals. Exercise trials were performed in a
      counterbalanced order for 3 d, separated by at least 3 d: TN, palm heating (PH),
      and PC. Heating and cooling were applied by placing the hand in a device called
      the rapid thermal exchanger, set to 45 degrees C for heating or 10 degrees C for
      cooling. This device heats or cools the palm while negative pressure (-35 to -45
      mm Hg) is applied around the hand. RESULTS: Total exercise volume during the four
      PC sets (2480 +/- 636 kg) was significantly higher than that during TN (1972 +/-
      632 kg) and PH sets (2156 +/- 668 kg, P < 0.01). The RMS of the surface EMG with
      PC exercise was higher (P < 0.01), whereas esophageal temperature (P < 0.05) and
      RPE (P < 0.05) were lower during PC compared with TN and PH. CONCLUSIONS: PC from
      35 degrees C to 20 degrees C temporarily overrides fatigue mechanism(s) during
      intense intermittent resistance exercise. The mechanisms for this ergogenic
      function remain unknown.

PMID- 20139783
TI  - Fatness, fitness, and cardiometabolic risk factors among sixth-grade youth.
AB  - PURPOSE: Examine whether cardiometabolic risk factors are predicted by fitness or
      fatness among adolescents. METHODS: Participants are 4955 (2614 female) sixth
      grade students with complete data from 42 US middle schools. Fasting blood
      samples were analyzed for total cholesterol, HDL- and LDL-cholesterol,
      triglyceride, glucose, and insulin concentrations. Waist circumference and blood
      pressure were assessed. Body mass index (BMI) was categorized as normal weight,
      overweight, or obese as a measure of fatness. Fitness was assessed using the
      multistage shuttle test and was converted into gender-specific quintiles. Gender
      specific regression models, adjusted for race, pubertal status, and household
      education, were run to identify whether BMI group predicted risk factors. Models
      were repeated with fitness group and both fitness and fatness groups as
      predictors. RESULTS: Means for each risk factor (except HDL, which was the
      reverse) were significantly higher (P < 0.0001) with increased fatness and
      differed across all BMI groups (P < 0.001). Waist circumference, LDL-cholesterol,
      triglycerides, diastolic blood pressure, and insulin were inversely associated
      with fitness (P < 0.001). When both fatness and fitness were included in the
      model, BMI was associated (P < 0.001) with almost all cardiometabolic risk
      factors; fitness was only associated with waist circumference (both genders), LDL
      cholesterol (males), and insulin (both genders). Other associations between
      fitness and cardiometabolic risk factors were attenuated after adjustment for BMI
      group. CONCLUSIONS: Both fatness and fitness are associated with cardiometabolic
      risk factors among sixth-grade youth, but stronger associations were observed for
      fatness. Although maintaining high levels of fitness and preventing obesity may
      positively affect cardiometabolic risk factors, greater benefit may be obtained
      from obesity prevention.

PMID- 20139784
TI  - Increased cardiometabolic risk is associated with increased TV viewing time.
AB  - PURPOSE: Television viewing time, independent of leisure time physical activity,
      has cross-sectional relationships with the metabolic syndrome and its individual
      components. We examined whether baseline and 5-yr changes in self-reported
      television viewing time are associated with changes in continuous biomarkers of
      cardiometabolic risk (waist circumference, triglycerides, HDL-cholesterol,
      systolic and diastolic blood pressure, fasting plasma glucose, and a clustered
      cardiometabolic risk score) in Australian adults. METHODS: The Australian
      Diabetes, Obesity and Lifestyle Study (AusDiab) is a prospective, population
      based cohort study with biological, behavioral, and demographic measures
      collected in 1999-2000 and 2004-2005. Noninstitutionalized adults aged > or =25
      yr were measured at baseline (11,247; 55% of those completing an initial
      household interview); 6400 took part in the 5-yr follow-up biomedical
      examination, and 3846 met the inclusion criteria for this analysis. Multiple
      linear regression analysis was used, and unstandardized B coefficients (95%
      confidence intervals (CI)) are provided. RESULTS: Baseline television viewing
      time (10 h.wk-1 unit) was not significantly associated with change in any of the
      biomarkers of cardiometabolic risk. Increases in television viewing time over 5
      yr (10 h.wk-1 unit) were associated with increases in waist circumference (men:
      0.43 cm, 95% CI = 0.08-0.78 cm, P = 0.02; women: 0.68 cm, 95% CI = 0.30-1.05, P <
      0.001), diastolic blood pressure (women: 0.47 mm Hg, 95% CI = 0.02-0.92 mm Hg, P
      = 0.04), and the clustered cardiometabolic risk score (women: 0.03, 95% CI = 0.01
      0.05, P = 0.007). These associations were independent of baseline television
      viewing time and baseline and change in physical activity and other potential
      confounders. CONCLUSIONS: These findings indicate that an increase in television
      viewing time is associated with adverse cardiometabolic biomarker changes.
      Further prospective studies using objective measures of several sedentary
      behaviors are required to confirm causality of the associations found.

PMID- 20139785
TI  - Relative workload determines exercise-induced increases in PGC-1alpha mRNA.
AB  - INTRODUCTION: The hypothesis that brief intermittent exercise-induced increases
      in human skeletal muscle metabolic mRNA is dependent on relative workload was
      investigated. METHODS: Trained (n = 10) and untrained (n = 8) subjects performed
      exhaustive intermittent cycling exercise (4 x 4 min at 85% of VO(2peak),
      interspersed by 3 min). Trained subjects also performed the intermittent exercise
      at the same absolute workload as the untrained subjects, corresponding to 70% of
      VO(2peak) (n = 6). RESULTS: Exercise at 85% of V(O2peak) elevated (P < 0.001)
      venous plasma lactate to 10.1 +/- 0.4 and 10.8 +/- 0.5 mM in the trained and
      untrained subjects, respectively. Peroxisome proliferator-activated receptor
      gamma coactivator 1alpha (PGC-1alpha) mRNA expression was increased (P < 0.001)
      approximately four- to fivefold for several hours after exercise in both groups.
      After exercise at 70% of VO(2peak), venous plasma lactate was less (P < 0.001)
      elevated (3.1 +/- 0.7 mM) and PGC-1alpha mRNA content was less (P < 0.05)
      increased (approximately threefold) than after exercise at 85% of VO(2peak).
      Likewise, pyruvate dehydrogenase kinase 4 and hexokinase II mRNA expressions were
      increased (P < 0.05) only after exercise performed at 85% of VO(2peak) in the
      trained subjects. Hypoxia-inducible factor 2alpha mRNA only increased (P < 0.05)
      3 h into recovery in trained subjects, with no difference between the 70% and 85%
      of VO(2peak) trial. No change in hypoxia-inducible factor 1alpha,
      phosphofructokinase, citrate synthase, or lactate dehydrogenase, heart and muscle
      isoforms, mRNA expressions was detected after any of the exercise trials.
      CONCLUSIONS: The relative intensity of brief intermittent exercise is of major
      importance for the exercise-induced increase of several mRNA, including PGC
      1alpha.

PMID- 20139787
TI  - Quiet eye duration and gun motion in elite shotgun shooting.
AB  - INTRODUCTION: No literature exists to document skill-related differences in
      shotgun shooting and whether these may be a function of eye movements and control
      of gun motion. We therefore conducted an exploratory investigation of the visual
      search behaviors and gun barrel kinematics used by elite and subelite shooters
      across the three shotgun shooting subdisciplines. METHODS: Point of gaze and gun
      barrel kinematics were recorded in groups of elite (n = 24) and subelite (n = 24)
      shooters participating in skeet, trap, and double trap events. Point of gaze was
      calculated in relation to the scene, while motion of the gun was captured by two
      stationary external cameras. Quiet eye (final fixation or tracking gaze that is
      located on a specific location/object in the visual display for a minimum of 100
      ms) duration and onset were analyzed as well as gun motion profiles in the
      horizontal and vertical planes. RESULTS: In skeet, trap, and double trap
      disciplines, elite shooters demonstrated both an earlier onset and a longer
      relative duration of quiet eye than their subelite counterparts did. Also, in all
      three disciplines, quiet eye duration was longer and onset earlier during
      successful compared with unsuccessful trials for elite and subelite shooters.
      Kinematic analyses indicated that a slower movement of the gun barrel was used by
      elite compared with subelite shooters. CONCLUSIONS: Overall, stable gun motion
      and a longer quiet eye duration seem critical to a successful performance in all
      three shotgun disciplines.

PMID- 20139786
TI  - Glycemic status affects cardiopulmonary exercise response in athletes with type I
      diabetes.
AB  - PURPOSE: This study aimed to (a) examine the influence of type I diabetes on the
      cardiopulmonary exercise response in trained subjects and (b) determine whether
      glycemic control affects these responses. METHODS: The cardiopulmonary responses
      to maximal incremental cycle ergometry were compared in 12 Ironman triathletes
      with type I diabetes and 10 age- and sex-matched control subjects without
      diabetes. Athletes with type I diabetes were then stratified into low-
      (glycosylated hemoglobin (HbA1c) < 7%, n = 5) and high-HbA1c (HbA1c > 7%, n = 7)
      groups for comparison. Cardiac output, stroke volume, arterial blood pressure,
      and calculated systemic vascular resistance along with airway function were
      measured at rest and during steady-state exercise. RESULTS: During peak exercise
      HR, stroke volume and cardiac output were not different between the groups with
      and without diabetes; however, forced expiratory flow at 50% of the forced vital
      capacity was lower in subjects with diabetes (P < 0.05). Within the group with
      diabetes, HbA1c was lower in the low-HbA1c versus high-HbA1c group (6.5 +/- 0.3
      vs 7.8 +/- 0.4, respectively; P < 0.05), but training volume was not different.
      At rest, the low-HbA1c group had greater cardiac output and lower systemic
      vascular resistance than the high-HbA1c group, and all pulmonary function
      measurements were greater in the low-HbA1c group (P < 0.05). During peak
      exercise, the VO2, workload, HR, stroke volume, and cardiac output were greater
      in the low-HbA1c versus the high-HbA1c group (P < 0.05). In addition, all indices
      of pulmonary function were higher in the low-HbA1c group (P < 0.05). Finally,
      within the subjects with diabetes, there was a weak inverse correlation between
      HbA1c and exercise training volume (r2 = -0.352) and stroke volume (r2 = -0.339).
      These data suggest that highly trained individuals with type I diabetes can
      achieve the same cardiopulmonary exercise responses as trained subjects without
      diabetes, but these responses are reduced by poor glycemic control.

PMID- 20139788
TI  - Applying generalizability theory to estimate habitual activity levels.
AB  - PURPOSE: Relative and absolute decisions in physical activity research are
      commonly based on a single assessment period that may not represent habitual
      activity behavior. This study used the generalizability theory to 1) quantify
      multiple sources of measurement error and 2) estimate the number of days and
      seasons needed to characterize long-term levels of activity. METHODS: Between
      2005 and 2006, youth participating in an intervention program were asked to wear
      a pedometer across seven consecutive days during three separate months
      (September, January, and May). Total variance in activity was partitioned and
      quantified according to differences among participants, inconsistency across
      days, relative differences among seasons, and the interactions among variables.
      Two coefficients (generalizability and phi) were calculated from multiple
      decision studies using a random and mixed design to determine the study protocol
      needed to achieve a reliability of 0.80 for relative and absolute decisions,
      respectively. Data were analyzed in 2009. RESULTS: Complete data were available
      for 42 boys and 38 girls. Residual variance accounted for the largest source of
      measurement error (55.64%), whereas smaller amounts were attributed to the
      participant (18.74%), season (6.59%), and day (2.67%) terms. Using a random
      design, both coefficients failed to reach an acceptable level of reliability
      using a single season. In contrast, using a mixed design, an acceptable level of
      reliability could be reached using 7-8 d from a single, fixed season.
      CONCLUSIONS: This study demonstrates the potential for using the generalizability
      theory to make decisions regarding the rank order of activity among individuals
      (relative decision) and compliance rates for physical activity recommendations
      (absolute decision).

PMID- 20139789
TI  - Osteogenic index and changes in bone markers during a jump training program: a
      pilot study.
AB  - PURPOSE: This study was designed as a proof-of-concept study to assess the
      osteogenic index (OI) and changes in bone markers during an 8-wk jump training
      program. On the basis of the OI, jumps were completed in one or two daily
      sessions with total jumps per day being equal. METHODS: Seven males served as
      controls and participated in their normal strength training program. Fourteen
      males were divided into two groups, jumping once daily (J1x) or jumping twice
      daily (J2x), with a 6-h recovery period between sessions (J2x only). Jumping-type
      exercises were performed on a Plyo Press and started at 20 plyo-jumps per day,
      three times per week and progressed to 60 plyo-jumps per day, three times per
      week for the last 3 wk. Blood samples were collected at baseline and at 4 and 8
      wk to determine serum concentrations of bone-specific alkaline phosphate and C
      terminal telopeptides of type I collagen. RESULTS: OI for each session and week
      were different (P < 0.05) between the two jumping groups (baseline OI per week,
      J1x = 28 +/- 0.9, J2x = 34 +/- 0.9). There was a significant change (P = 0.005)
      in bone-specific alkaline phosphate over time, with 8-wk values being
      significantly higher than baseline values (change from baseline: J1x = 2.7 +/-
      1.4 microg.L-1, J2x = 3.5 +/- 1.3 microg.L-1). J2x had an overall mean change
      significantly different from zero. C-terminal telopeptides of type I collagen did
      not change significantly during the 8 wk. CONCLUSIONS: The data demonstrate that
      the bone of young adult males does respond to a high-impact exercise. In
      addition, compared with completing all plyo-jumps in one session, the use of
      recovery periods between exercise sessions on the same day may result in positive
      changes in bone turnover, indicative of an osteogenic effect. The beneficial
      impact of the OI and how it can be used to design programs to influence bone
      turnover still remain to be determined.

PMID- 20139790
TI  - Effect of a simulated active commute to school on cardiovascular stress
      reactivity.
AB  - PURPOSE: Stress-induced cardiovascular reactivity is associated with the
      pathogenesis of cardiovascular disease. This study tested whether a simulated
      active commute to school dampened cardiovascular reactivity to a cognitive
      stressor typical to what children might experience during school. METHODS: Forty
      children (20 girls and 20 boys) aged 10-14 yr were randomly assigned to simulated
      sedentary drive-to-school or active-commute (walking) groups. The walking group
      completed a self-paced 1.6-km walk on a treadmill while images from a real 1.6-km
      walk through a pleasant neighborhood that finished at a school were projected in
      front of them. The drive-to-school group sat in a chair and watched the same
      slideshow of images of the neighborhood environment. Standardized residualized
      gain scores of cardiovascular reactivity during a cognitive stressor, the Stroop
      task, were calculated and used as dependent variables. RESULTS: Children in the
      walking group self-selected a walking intensity of 60.6% +/- 1.6% HRmax and
      covered the 1.6-km distance in 21.5 +/- 0.5 min. Children in the walking group
      had lower HR (2 +/- 1 vs 11 +/- 1 bpm, P < 0.001), systolic blood pressure (4 +/-
      1 vs 12 +/- 1 mm Hg, P < 0.001), pulse pressure (-4 +/- 1 vs 6 +/- 1 mm Hg, P <
      0.001), and perceived stress (1.4 +/- 0.1 vs 3.0 +/- 0.1 cm, P < 0.001)
      reactivities to cognitive stress than the control group. CONCLUSIONS: Active
      commuting to school may dampen cardiovascular reactivity and perceived stress
      when confronted with stressful cognitive challenges during the school day. This
      may help reduce the risk for cardiovascular disease later in life.

PMID- 20139791
TI  - Exercise enhances whole-body cholesterol turnover in mice.
AB  - PURPOSE: Regular exercise reduces cardiovascular risk in humans by reducing
      cholesterol levels, but the underlying mechanisms have not been fully explored.
      Exercise might provoke changes in cholesterol and bile acid metabolism and
      thereby reduce cardiovascular risk. We examined whether voluntary wheel running
      in mice modulates cholesterol and bile acid metabolism. METHODS: Male mice (10 wk
      old) were randomly assigned to have access to a voluntary running wheel for 2 wk
      (RUN group) or remained sedentary (SED group). Running wheel activity was
      recorded daily. In a first experiment, fecal sterol outputs, fecal bile acid
      profiles, plasma parameters, and expression levels of genes involved in
      cholesterol and bile acid metabolism were determined. In a second experiment,
      bile flow, biliary bile acid profile, and biliary secretion rates of cholesterol,
      phospholipids, and bile acids were determined. RESULTS: The RUN group ran an
      average of 10 km.d and displayed lower plasma cholesterol compared with SED (P =
      0.030). Fecal bile acid loss was induced by approximately 30% in running mice
      compared with SED (P = 0.0012). A approximately 30% increase in fecal cholesterol
      output in RUN (P = 0.014) was consistent with changes in parameters of
      cholesterol absorption, such as reduced plasma plant sterol-cholesterol ratio (P
      = 0.044) and decreased jejunal expression of Npc1l1 (P = 0.013). Supportive of an
      increased cholesterol synthesis to compensate for fecal sterol loss were
      increased hepatic mRNA levels of HMGCoA reductase (P = 0.006) and an increased
      plasma lathosterol-cholesterol ratio (P = 0.0011) in RUN. CONCLUSIONS: Voluntary
      wheel running increased cholesterol turnover in healthy mice owing to an
      increased fecal bile acid excretion and a decreased intestinal cholesterol
      absorption. Enhanced cholesterol turnover may contribute to the established
      reduction of cardiovascular risk induced by regular exercise.

PMID- 20139792
TI  - Assessing physical activity in persons with rheumatoid arthritis using
      accelerometry.
AB  - PURPOSE: To investigate empirically if the nonwear threshold and the "valid day"
      definition for accelerometer data from the general adult US population are
      appropriate for accelerometer data from persons with rheumatoid arthritis (RA).
      METHODS: This study analyzed data from 107 persons with RA participating in the
      baseline (2006-2008) accelerometer assessment from two studies with common
      inclusion/exclusion criteria. We examined candidate nonwear thresholds ranging
      from 20 to 300 min of zero activity count. The effect of the selected nonwear
      threshold is examined in regard to 1) mean daily activity counts, 2) activity
      counts per wear hour, 3) mean daily minutes of moderate to vigorous physical
      activity (MVPA) according to count thresholds that occur in 10-min bouts, and 4)
      MVPA bout minutes per wear hour. The effect of ranging the definition of a valid
      day of accelerometer data from 8 h of wear time to 12 h on data retention was
      also examined. RESULTS: In 737 d of accelerometer data analyzed, the average
      daily wear hours increased with length of nonwear threshold of allowed continuous
      zero activity count minutes. The mean number of nonzero activity count minutes
      increased with the chosen nonwear threshold until it stabilized at 478 min.d of
      activity, which corresponded to the 90-min nonwear threshold. Choosing this
      threshold and requiring at least 10 h of wear time to constitute a valid day were
      associated with 92.8% of days of collected data defined as "valid." CONCLUSIONS:
      Data supported increasing the allowed nonwear threshold in this RA subpopulation
      from 60 to 90 min, while retaining the 10-h day as the measure of the "valid
      day."

PMID- 20139793
TI  - Effect of exercise on oxidative stress: a 12-month randomized, controlled trial.
AB  - PURPOSE: This study examined the effect of a yearlong exercise intervention on F2
      isoprostane, a specific marker of lipid peroxidation and a general marker of
      oxidative stress. METHODS: In a randomized, controlled trial, 173 overweight or
      obese, postmenopausal, sedentary women were randomized either to an aerobic
      exercise intervention (60%-75% observed maximal HR) for > or =45 min.d-1, 5 d.wk
      1 (n = 87), or to a stretching control group (n = 86), on an intent-to-treat
      basis. Baseline and 12-month measures included urinary F2-isoprostane, maximal O2
      uptake, body weight, body fat percentage, waist circumference, and intra
      abdominal fat surface area. Urine samples were available from 172 and 168 women
      at baseline and 12 months, respectively. RESULTS: During the 12-month study,
      controls minimally changed maximal O2 uptake (+0.2%) and body weight (+0.1 kg),
      whereas exercisers increased maximal O2 uptake (+13.6%; P < 0.0001 vs controls)
      and decreased body weight (-1.3 kg; P = 0.007 vs controls). F2-isoprostane
      increased slightly among controls (+3.3%) and decreased in exercisers (-6.2%),
      although the effect was not statistically significant (P = 0.26). In planned
      subgroup analyses, F2-isoprostane decreased linearly with gain in maximal O2
      uptake (Ptrend = 0.005) relative to controls; exercisers who increased maximal O2
      uptake by >15% decreased F2-isoprostane by 14.1% (P = 0.005 vs controls). A
      borderline statistically significant trend was observed between decreased waist
      circumference and F2-isoprostane (P = 0.06). Similar subgroup analyses by 12
      month changes in body fat percentage, weight, and intra-abdominal fat were not
      statistically significant. CONCLUSIONS: These findings suggest that aerobic
      exercise, when accompanied by relatively marked gains in aerobic fitness,
      decreases oxidative stress among previously sedentary older women and that these
      effects occur with minimal change in mass or body composition.

PMID- 20139795
TI  - Nanotechnology: pediatric applications.
AB  - Ventilator-associated pneumonia (VAP) is a serious and costly clinical problem
      affecting pediatrics today. This device-related infection is thought to be
      directly linked to the colonization of the endotracheal tube (ETT) during long
      term mechanical ventilation. Because of unspecific radiographic and clinical
      signs, VAP is especially difficult to diagnose in the pediatric population.
      Treatment with antibiotics is often ineffective, and VAP is associated with high
      morbidity, mortality, and medical costs. The use of nanomodified coatings on ETT
      may provide an effective strategy to prevent biofilm formation and ETT
      colonization. Nanoparticles such as selenium and iron oxide have been shown to
      penetrate into the biofilm reaching the protected cells antibiotics often miss.
      Moreover, nanoetching techniques can modify the topography of the ETT surface
      interfering with bacterial adhesion. This review seeks to examine the
      antimicrobial properties of both nanoparticles and nanomodified surfaces and to
      characterize their effectiveness at reducing bacterial colonization on ETT.

PMID- 20139796
TI  - Molecular thermometry.
AB  - Conventional temperature measurements rely on material responses to heat, which
      can be detected visually. When Galileo developed an air expansion based device to
      detect temperature changes, Santorio, a contemporary physician, added a scale to
      create the first thermometer. With this instrument, patients' temperatures could
      be measured, recorded, and related to changing health conditions. Today, advances
      in materials science and bioengineering provide new ways to report temperature at
      the molecular level in real time. In this review, the scientific foundations and
      history of thermometry underpin a discussion of the discoveries emerging from the
      field of molecular thermometry. Intracellular nanogels and heat sensing
      biomolecules have been shown to accurately report temperature changes at the
      nanoscale. Various systems will soon provide the ability to accurately measure
      temperature changes at the tissue, cellular, and even subcellular level, allowing
      for detection and monitoring of very small changes in local temperature. In the
      clinic, this will lead to enhanced detection of tumors and localized infection,
      and accurate and precise monitoring of hyperthermia-based therapies. Some
      nanomaterial systems have even demonstrated a theranostic capacity for heat
      sensitive, local delivery of chemotherapeutics. Just as early thermometry rapidly
      moved into the clinic, so too will these molecular thermometers.

PMID- 20139797
TI  - Extensive splicing of transcripts encoding the bile acid-conjugating enzyme
      UGT2B4 modulates glucuronidation.
AB  - BACKGROUND AND AIMS: UGT2B4 is a member of the UDP-glucuronosyltransferase (UGT)
      superfamily, a major detoxifying system in humans. UGT2B4 is involved in bile
      acids metabolism and highly expressed in liver and extrahepatic tissues. The aim
      of this study was to uncover new molecular mechanisms underlying interindividual
      variability in the UGT2B4 pathway. METHODS: We carried out a comprehensive scan
      for additional exons at this locus and discovered multiple alternative splicing
      events. We then assessed the expression profile of alternatively spliced
      transcripts in human tissues and the activity of the corresponding overexpressed
      proteins toward bile acids. RESULTS: We discovered three previously unidentified
      UGT2B4 exons, increasing the total known gene length to 46 kb. Molecular analyses
      revealed at least eight distinct mRNAs produced by (i) alternative promoter
      usage, (ii) complete and partial exon skipping, and (iii) use of alternative 3'
      splice sites. These splice variants were predominantly expressed in liver,
      gastrointestinal tract, and other extrahepatic tissues. Quantitative analyses of
      splicing events further sustain their prevalence in the liver. UGT2B4 proteins
      produced from these mRNA variants had undetectable transferase activity in human
      cells. However, when stably co-expressed with the active UGT2B4 isoform 1, three
      newly identified UGT2B4 isoforms (i2, i3, and i5) were found to negatively
      regulate glucuronidation. CONCLUSION: In addition to heritable genetic mutations
      and control of gene expression, the newly discovered diversity of UGT2B4 mRNAs
      may introduce variability in this glucuronidation pathway.

PMID- 20139800
TI  - High-resolution optical coherence tomography shows new aspects of Bietti
      crystalline retinopathy.

PMID- 20139798
TI  - ADME pharmacogenetics: investigation of the pharmacokinetics of the
      antiretroviral agent lopinavir coformulated with ritonavir.
AB  - BACKGROUND: An ADME (absorption, distribution, metabolism and excretion)
      pharmacogenetics association study may identify functional variants relevant to
      the pharmacokinetics of lopinavir co-formulated with ritonavir (LPV/r), a first
      line anti-HIV agent. METHODS: An extensive search of literature and web resources
      helped select ADME genes and single nucleotide polymorphisms (SNPs, functional
      and HapMap tagging SNPs) with a proven or potentially relevant role in LPV/r
      pharmacokinetics. The study followed a two-stage design. Stage 1 (discovery)
      considered a Caucasian population (n=638) receiving LPV/r, where we selected 117
      individuals with low LPV clearance (cases) and 90 individuals with high clearance
      (controls). Genotyping was performed by a 1536-SNP customized GoldenGate Illumina
      BeadArray. Stage 2 (confirmation) represented a replication study of candidate
      SNPs from the stage 1 in 148 individuals receiving LPV/r. The analysis led to
      formal population pharmacokinetic-pharmacogenetic modeling of demographic,
      environmental and candidate SNP effects. RESULTS: One thousand three hundred and
      eighty SNPs were successfully genotyped. Nine SNPs prioritized by the stage 1
      analysis were brought to replication. Stage 2 confirmed the contribution of two
      functional SNPs in SLCO1B1, one functional SNP in ABCC2 and a tag SNP of the
      CYP3A locus in addition to body weight effect and ritonavir coadministration.
      According to the population pharmacokinetic-pharmacogenetic model, genetic
      variants explained 5% of LPV variability. Individuals homozygous rs11045819
      (SLCO1B1*4) had a clearance of 12.6 l/h, compared with 5.4 l/h in the reference
      group, and 3.9 l/h in individuals with two or more variant alleles of rs4149056
      (SLCO1B1*5), rs717620 (ABCC2) or rs6945984 (CYP3A). A subanalysis confirmed that
      although a significant part of the variance in LPV clearance was attributed to
      fluctuation in ritonavir levels, genetic variants had an additional effect on LPV
      clearance. CONCLUSION: The two-stage strategy successfully identified genetic
      variants affecting LPV/r pharmacokinetics. Such a general approach of ADME
      pharmacogenetics should be generalized to other drugs.

PMID- 20139801
TI  - An elementary and effective method for silicone oil removal.

PMID- 20139802
TI  - Micromass culture of human anulus cells: morphology and extracellular matrix
      production.
AB  - STUDY DESIGN: Micromass culture was assessed as a cell culture microenvironment
      for anulus cells from the human intervertebral disc. OBJECTIVE: To determine
      whether the micromass culture technique might be useful for the culture of human
      anulus cells. SUMMARY OF BACKGROUND DATA: Culture of cells in micromass has been
      traditionally used as a method to culture chondrocytes in a three-dimensional
      (3D) microenvironment with specialized chondrocyte media which allows expression
      of the chondrocytic phenotype. Recently it has also been used for disc cell 3D
      culture. METHODS: Following approval of our human subjects Institutional Review
      Board, cells isolated from human anulus intervertebral disc tissue was cultured
      in micromass culture under control conditions or with addition of 5 ng/mL
      transforming growth factor-beta (TGF-beta). Cultures were grown for 7 days, and
      then analyzed for morphology with light microscopy, for extracellular matrix
      (ECM) production with transmission electron microscopy and quantitative
      measurement of total sulfated proteoglycan production. Immunohistochemistry was
      also performed to assess types I and II collagen, decorin, keratan sulfate, and
      chondroitin sulfate content of ECM. RESULTS: Human anulus cells form multilayered
      colonies when cultured with minimal media and 20% fetal bovine serum in the
      micromass methodology. Stimulation of ECM production occurs when 5 ng/mL TGF-beta
      was added to the micromass media. TGF-beta also significantly increased the
      production of sulfated proteoglycans (P = 0.026). Under both control and TGF-beta
      supplementation, the resulting micromass formed by anulus cells is not as compact
      as the micromass which results when stem cells cultured in chondrogenic media.
      Ultrastructural studies showed the presence of apoptotic cells and the presence
      of peroxisomes within cells. Immunohistochemical studies on production of type I
      collagen, decorin and keratan sulfate showed that there was localized production
      of these ECM components in focal regions; chondroitin sulfate and type II
      collagen, however, showed a more uniform overall production by cells within the
      micromass. CONCLUSION: Human anulus cells were successfully cultured under
      micromass conditions in nonchondrogenic media and with TGF-beta supplementation
      which increased ECM production. The resulting anulus cell micromass, however, was
      not as rounded or compact as that which occurs with routine chondrocyte micromass
      or stem cells induced into chondrocyte differentiation. The presence of
      peroxisomes noted on ultrastructural studies may reflect cell stress or uneven
      distribution of nutrition within the micromass during the 7-day micromass culture
      period. Immunohistochemical studies showed nonuniform ECM gene expression and
      production within the micromass, suggesting variable gene expression patterns
      with this culture method.

PMID- 20139803
TI  - C-arm cone beam computed tomography needle path overlay for fluoroscopic guided
      vertebroplasty.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To report our early clinical
      experience using C-arm cone beam computed tomography (C-arm CBCT) with
      fluoroscopic overlay for needle guidance during vertebroplasty. SUMMARY OF
      BACKGROUND DATA: C-arm CBCT is advanced three-dimensional (3-D) imaging
      technology that is currently available on state-of-the-art flat panel based
      angiography systems. The imaging information provided by C-arm CBCT allows for
      the acquisition and reconstruction of "CT-like" images in flat panel based
      angiography/interventional suites. As part of the evolution of this technology,
      enhancements allowing the overlay of cross-sectional imaging information can now
      be integrated with real time fluoroscopy. We report our early clinical experience
      with C-arm CBCT with fluoroscopic overlay for needle guidance during
      vertebroplasty. METHODS: This is a retrospective review of 10 consecutive
      oncology patients who underwent vertebroplasty of 13 vertebral levels using C-arm
      CBCT with fluoroscopic overlay for needle guidance from November 2007 to December
      2008. Procedural data including vertebral level, approach (transpedicular vs.
      extrapedicular), access (bilateral vs. unilateral) and complications were
      recorded. Technical success with the overlay technology was assessed based on
      accuracy which consisted of 4 measured parameters: distance from target to needle
      tip, distance from planned path to needle tip, distance from midline to needle
      tip, and distance from the anterior 1/3 of the vertebral body to needle tip.
      Success within each parameter required that the distance between the needle tip
      and parameter being evaluated be no more than 5 mm on multiplanar CBCT or
      fluoroscopy. RESULTS: Imaging data for 12 vertebral levels was available for
      review. All vertebral levels were treated using unilateral access and 9 levels
      were treated with an extrapedicular approach. Technical success rates were 92%
      for both distance from planned path and distance from midline to final needle
      tip, 100% when distance from needle tip to the anterior 1/3 border of the
      vertebral body was measured, and 75% when distance from target to needle tip was
      measured. There were no major complications. Minor complications consisted of 3
      cases (25%) of cement extravasation. CONCLUSION: C-arm CBCT with needle path
      overlay for fluoroscopic guided vertebroplasty is feasible and allows for
      reliable unilateral therapy of both lumbar and thoracic vertebral bodies.
      Extrapedicular approaches were performed safely and with good accuracy of
      reaching the targets.

PMID- 20139804
TI  - Lumbar axial loading device alters lumbar sagittal alignment differently from
      upright standing position: a computed tomography study.
AB  - STUDY DESIGN: A study was performed using an axial loading device in healthy
      young subjects. OBJECTIVE: To determine whether sagittal alignment during axial
      loading using a compression device can accurately simulate the standing posture.
      SUMMARY OF BACKGROUND DATA: Axial compression devices are widely used for
      simulation of standing position during magnetic resonance imaging (MRI) or
      computed tomography (CT) scans. However, images taken during axial loading have
      not been compared with those obtained in a standing posture. METHODS: The study
      population comprised 14 asymptomatic healthy volunteers (7 men and 7 women: age
      21-32, mean 27 years). Lumbar lateral radiograph films obtained in the standing
      posture (standing condition), lumbar CT images with axial loading using a
      DynaWell compression device (axial loading condition), and CT images without
      loading (control) were compared. Changes in spinal length, lumbar disc height,
      segmental lordotic angle, and total lumbar lordotic angle were compared among the
      conditions. RESULTS: Spinal length was significantly decreased in both the axial
      loading and standing conditions compared with controls. The magnitude of the
      changes was greater in the standing condition than in the axial loading
      condition. Segmental lordotic angle at L2/3 and L3/4 was significantly increased
      in both axial loading and standing conditions. However, disc lordotic angle at
      L5/S was significantly decreased in the axial loading condition, while the
      standing condition showed no significant change. Consequently, the pelvic angle
      showed a significant decrease in the axial loading condition. CONCLUSION: The
      compression device simulates the lumbar segmental alignment change from supine to
      standing posture in L1/2, L2/3, L3/4, and L4/5. However, in L5/S, axial loading
      using the DynaWell altered lumbar segmental alignment with a kyphotic change,
      while no significant difference was observed in this level between standing and
      supine positions. Awareness of these phenomena are essential for accurate
      interpretation of imaging results.

PMID- 20139805
TI  - Bone morphogenetic protein-2 and bone marrow aspirate with allograft as
      alternatives to autograft in instrumented revision posterolateral lumbar spinal
      fusion: a minimum two-year follow-up study.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Compare the efficacy of
      rhBMP-2 and bone marrow aspirate with allograft (BMAA) as alternatives to
      autograft in instrumented revision posterolateral lumbar fusion (PLF). SUMMARY OF
      BACKGROUND DATA: The use of autogenous bone graft is the current gold standard in
      revision PLF; however, this practice is associated with significant donor-site
      morbidity. Revision PLF pose the additional challenges of a less than ideal
      fusion environment and a limited quantity of autogenous bone graft. rhBMP-2 and
      BMAA have been shown to be acceptable bone graft substitutes in several primary
      orthopedic procedures. The role of these bone graft substitutes in instrumented
      revision PLF has yet to be determined. METHODS: Sixty-two patients (125 levels)
      who underwent instrumented revision PLF with a minimum 2-year follow-up were
      included. Group 1 contained 24 patients (13 single- [group 1A] and 11 multilevel
      [group 1B]) who underwent instrumented revision PLF using rhBMP-2 on an
      absorbable collagen sponge. Group 2 included 18 patients (7 single- [group 2A]
      and 11 multilevel [group 2B]) with procedures using BMAA. Group 3 consisted of 20
      patients (10 single- [group 3A] and 10 multilevel [group 3B]) with procedures
      using autograft. Demographic, surgical, and clinical data were collected from
      medical records. Time to solid fusion mass formation, fusion rate, complications,
      and clinical outcomes were evaluated. The progression of the fusion mass was
      evaluated by reviewing radiographs. A diagnosis of nonunion was based on
      exploration during an additional revision surgery or evidence of nonunion on
      dynamic radiographs or computerized tomography. Clinical outcomes were assessed
      using a visual analog scale (VAS) before surgery and at 6-week, 6-, 12-, and 24
      month follow-ups. RESULTS: Overall fusion rate was 93.5% (58/62). All single
      level revision PLF achieved solid fusion. Groups 1B and 3B achieved 100% fusion,
      (11/11) and (10/10), respectively;whereas group 2B had a fusion rate of 63.6%
      (7/11). Group 1 also developed a solid fusion mass earlier than the other groups.
      There was a significant decrease between preoperative and 2-year postoperative
      VAS scores in all groups, but no significant difference among groups. Three
      patients in group 2 required an additional revision surgery. CONCLUSION: rhBMP-2
      may be an appropriate alternative to autogenous bone graft in both single- and
      multilevel revision PLF, whereas BMAA may be appropriate as a substitute in
      single-level revision PLF. The use of BMAA in single-level revisions may be a
      more cost-effective option than rhBMP-2.

PMID- 20139806
TI  - Variations in pelvic and other sagittal spinal parameters as a function of race
      in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A retrospective review of clinical and radiographic data from a
      multicenter adolescent idiopathic scoliosis (AIS) database. OBJECTIVE.: The
      purpose of this study was to perform a comprehensive radiographic evaluation of
      the differences in pelvic parameters between 2 groups (white and black) in a
      scoliotic population. SUMMARY OF BACKGROUND DATA: Increasingly, the importance of
      spinopelvic alignment and balance is appreciated as a major factor in the energy
      efficient posture of the individual in the normal and diseased states. Pelvic
      incidence (PI) determines the lordosis of the patient and equations defining the
      interplay of pelvic parameters, lordosis, and kyphosis have been developed to
      guide surgical decision-making for spinal deformity. PI and thoracic lordosis
      have been previously shown to be increased in the AIS population. METHODS: Data
      were obtained from a prospective multicenter AIS database from a total of 1658
      patients. We evaluated the 2 largest racial subsets in our database. We
      identified 421 whites and 115 black patients who met inclusion criteria. The
      parameters evaluated on preoperative full-length coronal and lateral radiographs
      were PI, sacral slope (SS), pelvic tilt, lumbar lordosis (LL), thoracic kyphosis,
      sagittal Cobb angle, and the shift of the sagittal C7 plumb line. RESULTS: Age,
      gender, major and minor cobb angles were similar in the 2 groups. PI, pelvic
      tilt, and LL were found to be significantly greater in the black group when
      compared with the white group (black: 56.0, 13.9, and -63.6 vs. white: 52.5,
      10.8, and -59.1). CONCLUSION: In our study, significant differences were found in
      3 of the 6 sagittal plane parameters between the 2 groups. With a larger PI, a
      larger LL is required in order maintain a neutral sagittal balance. Our results
      suggest that race may influence an individual's natural spinopelvic alignment,
      and serves as a reminder when planning surgical reconstruction for spinal
      deformity.

PMID- 20139807
TI  - Cross-cultural adaptation and clinimetric property of Korean version of the
      Chronic Pain Coping Inventory-42 in patients with chronic low back pain.
AB  - STUDY DESIGN: Validation of a translated, culturally adapted questionnaire.
      OBJECTIVE: We developed a Korean version of the Chronic Pain Coping Inventory-42
      (CPCI-42) by performing a cross-cultural adaptation, and evaluated its
      reliability and validity. SUMMARY OF BACKGROUND DATA: The CPCI is widely used and
      validated instruments for measuring coping strategies in chronic pain. However,
      no validated and culturally adapted version was available in Asian countries.
      METHODS: We assessed 142 patients with chronic low back pain using the CPCI-42
      and measures of physical disability, pain, and quality of life. Results for 93 of
      the 142 patients exhibited test-retest reliability. The interval time of
      collecting retest data varied from 2 weeks to 1 month. Criterion validity was
      evaluated using correlations between the CPCI-42 and the Oswestry Disability
      Index, the Brief Pain Inventory, and the Short Form 36-item Health Survey
      (version 2.0). Construct validity was computed using exploratory factor analysis.
      RESULTS: The Korean version of the CPCI-42 had a high internal consistency
      (Cronbach's alpha >0.70) with the exception of results for task persistence and
      relaxation. Illness-focused coping (guarding, resting, asking for assistance) and
      other-focused coping (seeking social support) were most significantly correlated
      with Oswestry Disability Index, Brief Pain Inventory, and Short Form 36-item
      Health Survey, respectively. Outcomes for task persistence were contrary to other
      subscales in wellness-focused coping. Construct validity by factor analysis
      produced similar results to the original CPCI subscale. However, several factors
      showed cross-loading in 8 factor solutions. CONCLUSION: Despite linguistic and
      cultural differences, the Korean version of the CPCI-42 is overall a meaningful
      tool, and produces results sufficiently similar to the original CPCI-42.

PMID- 20139808
TI  - How does surgery affect sexual desire and activities in patients with lumbar disc
      herniation?
AB  - STUDY DESIGN: A retrospective survey using privacy-conscious questionnaires.
      OBJECTIVE: To determine the quality and frequency of sexual activities in
      patients with lumbar disc herniation before and after surgery. SUMMARY OF
      BACKGROUND DATA: Patients and health care professionals often hesitate to talk
      about the effects of disease, illness, or surgery on sexuality, but it is
      imperative that sexuality issues be addressed. METHODS: Of 90 consecutive
      patients, 64 who had surgically-treated lumbar disc herniation participated in
      this survey after informed consent. There were 43 males and 21 females with mean
      age of 36 years. Duration of symptom was averaged 42 weeks. The patients were
      asked to complete questionnaires concerning sexual desire, activity, adjustment,
      and satisfaction. About 83% of the patients had sexual desire, and 89% achieved
      satisfaction during sexual activities in presick period. RESULTS: Lumbar disc
      herniation decreased sexual desire in 50% and frequency of sexual activity in 59%
      of the patients. About 67% of males and 81% of females felt discomfort during
      sexual activity; satisfaction decreased in 28% of male and 41% of females.
      Adjustment in sexual position was required in 54% of males and 86% of females.
      Surgery improved sexual desire, frequency of sexual activity, and satisfaction in
      85%, 88%, and 94%, respectively. However, 31% of females did not regain sexual
      desire and 46% still felt discomfort during sexual activity (the rates were 7%
      and 17% in males, respectively). Sexual activity was resumed within 2
      postoperative weeks in 23% (27% in males and 14% in females), and 4 weeks in 53%.
      Males resumed sexual activity earlier than females. CONCLUSION: Lumbar disc
      herniation largely impacted sexual desire, activity, and satisfaction. Adjustment
      in sexual position was required in large number of patients to avoid discomfort
      during sexual activities. Surgical treatment improved quality of sexual
      activities, but more females did not regain sexual desire, felt sexual
      discomfort, and thereby resumed sexual activities later than males after surgery.

PMID- 20139809
TI  - Appropriateness criteria for surgery improve clinical outcomes in patients with
      low back pain and/or sciatica.
AB  - STUDY DESIGN: Prospective, controlled, observational outcome study using
      clinical, radiographic, and patient/physician-based questionnaire data, with
      patient outcomes at 12 months follow-up. OBJECTIVE: To validate appropriateness
      criteria for low back surgery. SUMMARY OF BACKGROUND DATA: Most surgical
      treatment failures are attributed to poor patient selection, but no widely
      accepted consensus exists on detailed indications for appropriate surgery.
      METHODS: Appropriateness criteria for low back surgery have been developed by a
      multispecialty panel using the RAND appropriateness method. Based on panel
      criteria, a prospective study compared outcomes of patients appropriately and
      inappropriately treated at a single institution with 12 months follow-up
      assessment. Included were patients with low back pain and/or sciatica referred to
      the neurosurgical department. Information about symptoms, neurologic signs, the
      health-related quality of life (SF-36), disability status (Roland-Morris), and
      pain intensity (VAS) was assessed at baseline, at 6 months, and at 12 months
      follow-up. The appropriateness criteria were administered prospectively to each
      clinical situation and outside of the clinical setting, with the surgeon and
      patients blinded to the results of the panel decision. The patients were further
      stratified into 2 groups: appropriate treatment group (ATG) and inappropriate
      treatment group (ITG). RESULTS: Overall, 398 patients completed all forms at 12
      months. Treatment was considered appropriate for 365 participants and
      inappropriate for 33 participants. The mean improvement in the SF-36 physical
      component score at 12 months was significantly higher in the ATG (mean: 12.3
      points) than in the ITG (mean: 6.8 points) (P = 0.01), as well as the mean
      improvement in the SF-36 mental component score (ATG mean: 5.0 points; ITG mean: 
      0.5 points) (P = 0.02). Improvement was also significantly higher in the ATG for
      the mean VAS back pain (ATG mean: 2.3 points; ITG mean: 0.8 points; P = 0.02) and
      Roland-Morris disability score (ATG mean: 7.7 points; ITG mean: 4.2 points; P =
      0.004). The ATG also had a higher improvement in mean VAS for sciatica (4.0
      points) than the ITG (2.8 points), but the difference was not significant (P =
      0.08). The SF-36 General Health score declined in both groups after 12 months,
      however, the decline was worse in the ITG (mean decline: 8.2 points) than in the
      ATG (mean decline: 1.2 points) (P = 0.04). Overall, in comparison to ITG
      patients, ATG patients had significantly higher improvement at 12 months, both
      statistically and clinically. CONCLUSION: In comparison to previously reported
      literature, our study is the first to assess the utility of appropriateness
      criteria for low back surgery at 1-year follow-up with multiple outcome
      dimensions. Our results confirm the hypothesis that application of
      appropriateness criteria can significantly improve patient outcomes.

PMID- 20139810
TI  - Finite element analysis of the effects of pedicle screw fixation nut loosening on
      lumbar interbody fusion based on the elasto-plateau plasticity of bone
      characteristics.
AB  - STUDY DESIGN: Cylindrical cages and pedicle screw fixation (PSF) have been used
      for the setting of a lumbar interbody fusion. OBJECTIVE: To investigate the
      effects of PSF-nut loosening on lumbar interbody fusion based on the elasto
      plateau plasticity of bone characteristics. SUMMARY OF BACKGROUND DATA: The
      stress-strain curves of bone materials beneath the cages show linear elastic
      behavior before yielding and then seem to be plateau plastic deformation with
      further compression strain until opposing cell walls contact. METHODS: Cancellous
      bone was assumed to be linearly elastic followed by nonlinearly plastic such as
      crushable foam behavior. The deformation and failure processes caused by
      loosening of PSF-nuts, in particular, are addressed by means of finite element
      analysis. Two finite element models, including anterior (or posterior) lumbar
      interbody fusion for the human lumbar L4-L5 segments, were constructed. In the
      respective models, 2 types of PSF were considered such as a solid PSF without
      relative movement between rod and screw, and a tightened PSF with relative axial
      movement of the rod between them due to the slight loosening of 2 nuts of L4.
      RESULTS: The slight loosening of nuts showed much greater levels of bone strain
      with relative motion at the bone-implant interface compared with the PSF with
      firmly tightened nuts. The loosening 2 of the 4 nuts imposed an excessive burden
      on the remaining screws. CONCLUSION: By the consideration of the elasto-plateau
      plastic behavior of cancellous bone and the relative motion at the contact
      interface between screw and rod, much more exact behaviors of bone failure were
      predicted. Slight loosening of the nut would cause a possible risk of segmental
      instability. With difficulty in either tightening the nut firmly during actual
      operation or keeping the nut-locking mechanism functioning perfectly in the
      postoperative state, an enhanced design methodology with more effective locking
      mechanism is required. Slight PSF-nut loosening may increase risks of failure
      processes such as rod migration, rod breakage, screw breakage, screw loosening or
      cage loosening. Different mechanisms however, can be considered; rod breakage and
      screw breakages are related to the higher stress level of the rod and screw while
      rod migration is associated with slight nut-loosening. Especially, in the case of
      a nonsymmetric nut-loosening the risk would be increased. Thus, further study is
      necessary for improving the current design of PSFs.

PMID- 20139811
TI  - Closed suction irrigation for the treatment of postoperative wound infections
      following posterior spinal fusion and instrumentation.
AB  - STUDY DESIGN: Retrospective review of clinical cases. OBJECTIVE: This study
      describes the success rate of closed suction irrigation system (CSIS) in the
      treatment of post operative spinal infections. SUMMARY OF BACKGROUND DATA: Given
      the widening use of spinal instrumentation, the management of related
      postoperative deep wound infections has become increasingly important. In the
      literature, there have been reports of several treatment methods yet no firmly
      established protocol for management of postoperative deep wound infections
      exists. The goal of this study was to determine the effectiveness of our protocol
      employing (CSIS) in the treatment of postoperative deep wound infections.
      METHODS: A retrospective record review of 500 posterior instrumented fusions
      between 1990 and 2002. Twenty-eight consecutive infections (5%) were diagnosed
      and treated by a standardized treatment protocol of Incision and Drainage, and
      CSIS. Cultures were obtained, wounds closed primarily, and appropriate
      intravenous antibiotic treatments initiated. For statistical evaluation, patients
      were assigned a risk factor (RF) described by Levi et al (J Neurosurg.
      1997;86:975-980). Point values were assigned to medical comorbidities that may
      contribute to postoperative infection risk; higher RF values indicate an
      increased risk. RESULTS: Twenty-one acute and 7 late (>6 months) infections were
      followed for 22.3 months (1-86 months), post-CSIS treatment. Twenty-one (75%)
      resolved without recurrence with one CSIS treatment. Seven acute infections (25%)
      required a second course of treatment. Hospitalization for the index procedure
      averaged 15.4 days; 28.9 days for reinfections. No patient with an acute
      infection required implant removal. The reinfection group had higher blood loss,
      more levels fused, and longer hospitalization. The reinfection group was
      comprised entirely of pediatric patients. CONCLUSION: No correlation was found
      between RF values and greater risk of recurrent infection. Removal of implants is
      unnecessary in acute infections, provided the infection does not return. CSIS is
      an effective method for treatment of postoperative wound infections following
      instrumented spinal fusion avoiding the need for secondary closure.

PMID- 20139813
TI  - Validity of a computer touch-screen questionnaire system in back patients.
AB  - STUDY DESIGN: Validation study. OBJECTIVE: A system for patient self-recording on
      a computer touch-screen was developed. The validity of this method compared with
      the use of regular paper-and-pen questionnaires was studied. SUMMARY OF
      BACKGROUND DATA: Systematic evaluation of health problems often involves the use
      of self-reporting questionnaires in order to collect data on different variables.
      Recording of such data for subsequent analysis requires several steps including
      filling out of paper forms and secretarial work. Missing values and misrecordings
      are frequent problems. METHODS: Seventy-nine patients with back problems visiting
      our outpatient clinic for surgical evaluation were invited to take part in the
      study by answering a mailed questionnaire concerning background data, pain,
      function, quality of life, and depressive symptoms approximately 3 weeks before
      their visit. At the day of the visit they were asked to again answer the same
      questions with a replicate response option format displayed on a computer touch
      screen. RESULTS: The agreement concerning background history questions, measured
      by kappa values was generally good (0.71-1.0). For visual analogue scale
      recordings (0-100) of back and leg pain, the mean of the differences were 1.1 and
      2.1, respectively, and the correlations (Pearson) 0.72 and 0.87. The Euro-Qol 5
      Dimension Score, the General Function Score, the Zung Depression Scale and the
      physical dimensions of the Short Form-36 showed a high degree of agreement
      between paper and screen recordings with difference means close to 0 and
      reliabilities comparing well to published methodologic errors for paper form
      versions. There were, however, differences concerning the mental components of
      the SF-36 with somewhat higher ratings on screen recordings. Missing values were
      0% for screen recordings and for paper forms, 2.3% on individual questions and
      12% on composite scores. CONCLUSION: Computerized touch-screen questionnaires
      virtually eliminates missing values and show good validity and reliability
      compared to paper forms. The SF-36 tended to produce slightly higher values on
      touch-screen recordings in questions concerning mental health.

PMID- 20139814
TI  - Spontaneous transition of an autonomously functioning thyroid adenoma to Graves'
      disease.
AB  - We report a case of a 57-year-old postmenopausal woman with an autonomously
      functioning thyroid adenoma spontaneously developing Graves' disease (GD) as
      documented by I-123 scintigraphy. To date, anecdotal case reports citing the
      progression of an autonomous nodule to GD have documented either a major
      thyroidal insult, spontaneous or therapeutic, or the activation of thyroid tissue
      by circulating thyroid stimulating IgG, with variable progression
      characteristics. In contradiction to the proposed inciting factors, our patient
      underwent a minimally invasive fine needle aspiration biopsy followed by
      suppressive pharmacotherapy. Her antithyroid antibody assay detected low titers
      of thyroperoxidase antibody (<10 U/mL). We conclude that this is a rare case of
      autonomously functioning adenoma where neither significant thyroid tissue damage
      nor the presence of thyroid stimulating IgG can be implicated as an inciting
      trigger in its progression to GD.

PMID- 20139812
TI  - Back and neck pain and psychopathology in rural sub-Saharan Africa: evidence from
      the Gilgel Gibe Growth and Development Study, Ethiopia.
AB  - STUDY DESIGN: Community-based cross-sectional analysis of the relation between
      symptoms of psychopathology and back pain (BP) or neck pain (NP) in rural
      southwest Ethiopia. OBJECTIVE: Using data from a community-based sample, we
      assessed the prevalence and psychopathologic correlates of BP or NP in rural sub
      Saharan Africa. SUMMARY OF BACKGROUND DATA: BP and NP are among the most
      prevalent pain conditions. Psychopathology has been shown to be associated with
      both BP and NP in developed and urban developing contexts. Little is known about
      the relation between psychopathology and BP or NP in the rural, developing
      context. METHODS: Data on self-reported BP and NP, symptoms of depression,
      anxiety, and post-traumatic stress (PTS), gender, age, and socioeconomic status
      were collected from a representative cohort sample (N = 900) in rural southwest
      Ethiopia. We calculated univariate statistics to assess the prevalence of BP and
      NP. We used bivariate chi2 tests and multivariate logistic regression models to
      assess the relation between psychopathology and BP and NP. RESULTS: The
      prevalence of BP was 16.7%; that of NP was 5.0%. In chi2 analyses, symptoms of
      depression, anxiety, and PTS were significantly associated with increased risk
      for each outcome. In models adjusted for age, household assets, and gender,
      depression symptomatology was associated with increased risk for BP (OR = 3.44,
      95% CI: 2.37-5.00) and NP (OR = 4.92, 95% CI: 2.49-9.74). Anxiety symptomatology
      was also associated with increased risk for BP (OR = 2.88, 95% CI: 1.98-4.20) and
      NP (OR = 2.67, 95% CI: 1.41-5.09). PTS symptomatology was associated with
      increased risk for BP (OR = 2.89, 95% CI: 1.78-4.69). CONCLUSION: In the first
      known study about the relation between psychopathologic symptomatology and BP and
      NP in a rural context in a developing country, the prevalence of BP and NP were
      comparable to published data in developed and developing countries. Symptoms of
      depression and anxiety were correlates of BP and NP, and symptoms of PTS were a
      correlate of BP. Comparative studies about the relation between psychopathology
      and chronic pain conditions between rural and urban contexts in the global south
      are needed.

PMID- 20139815
TI  - FDG PET-CT in the management of primary breast lymphoma.
AB  - OBJECTIVE: Primary breast lymphoma (PBL) is a rare disease and its management
      differs from other breast cancers. The purpose of this study is to evaluate the
      role of FDG PET-CT in the management of PBL. We carried out 16 PET-CT scans and
      reviewed the literature. MATERIALS AND METHODS: A total of 16 FDG PET-CT scans
      were done in 8 female patients with PBL with a median age of 49 years (range: 27
      68). Of the 16 PET-CT scans, 1 scan was done for primary diagnosis and staging (1
      patient), 2 for staging (2 patients), 7 for evaluation of treatment response (6
      patients), and 6 for detecting recurrence (4 patients). PET-CT image
      interpretation and analysis were performed qualitatively (visually) and
      semiquantitatively using standardized uptake value (SUV). Absence of uptake in
      the postchemotherapy follow-up PET-CT scan was considered as a complete response,
      and a fall of more than 50% of baseline SUV was considered as a significant
      response. RESULTS: One patient was successfully diagnosed to have PBL and staged
      using PET-CT. Two patients were correctly staged with the help of FDG PET-CT.
      Complete response was noted in all 6 patients (3 had a positive baseline scan and
      showed complete resolution of FDG uptake, the other 3 who did not have baseline
      PET-CT and lesions were detected on CT, and also showed complete resolution). Of
      the 4 patients evaluated for recurrence, 1 patient was positive and 3 patients
      were negative for recurrence in follow-up PET-CT scans done after 18, 22, and 24
      months, respectively. CONCLUSION: FDG PET-CT has a definitive role in every step
      of management (diagnosis, staging, treatment response evaluation, and detection
      of recurrence) in patients with primary breast lymphoma.

PMID- 20139816
TI  - Problematic aspects of sentinel lymph node biopsy and its relation to previous
      excisional biopsy in breast cancer.
AB  - PURPOSE: The aim of the study is to review problematic aspects of sentinel lymph
      node biopsy (SLNB) and to evaluate the influence of a previous excisional biopsy
      on these problems. MATERIALS AND METHODS: A total of 345 patients were evaluated
      retrospectively, 156 of them had a previous biopsy. Tc-99m tin colloid was
      injected the day before surgery at 4 quadrants around the areola intradermally.
      Problems complicating SLNB are reviewed in 3 topics: visualization or gamma probe
      detection problems, dilated lymphatic channels, and misleading activity
      accumulation. RESULTS: SLN detection rate and mean sentinel lymph node numbers
      were as follows in patients with and without biopsy, respectively: 95.5% versus
      99.4% and 1.71 +/- 0.97 versus 1.70 +/- 0.92. Problems complicating the procedure
      occurred in 20 patients (5.8%). Among these 20 patients, 15 had a prior
      excisional biopsy, and incisions were located in the upper, outer and periareolar
      zones. Visualization or gamma probe detection problems occurred in 8 patients.
      Except for one with faint uptake in a sentinel node, all had a prior biopsy.
      Lymphatic channel dilatation complicated the procedure in 7 patients. Of these 7
      patients, 4 had a previous biopsy. Misleading activity accumulations compromised
      SLNB in 5 patients, 4 of whom had a prior biopsy. CONCLUSION: Although SLNB is
      still applicable with a high success rate in cases with excisional biopsy, a
      review of problematic aspects of SLNB demonstrated a relation with the presence
      of a previous biopsy and its localization. The demonstration of nonvisualization
      preoperatively and the precise localization of atypically located activity
      accumulation may be helpful in the prevention of potential complications.

PMID- 20139817
TI  - Sentinel node mapping in vulvovaginal melanoma using SPECT/CT lymphoscintigraphy.
AB  - We report 2 cases of vulvovaginal melanoma in which sentinel node mapping,
      performed using Tc-99m filtered sulfur colloid SPECT/CT lymphoscintigraphy, added
      important information to that provided by planar imaging and played a critical
      role in surgical planning and subsequent management. In the first case,
      lymphoscintigraphy planar imaging showed only foci of tracer uptake in the right
      groin and an equivocal focus in the left groin. SPECT/CT precisely localized
      these radioactive foci to the right and left inguinal sentinel nodes. The patient
      then underwent bilateral inguinal sentinel node sampling. In the second case, F
      18 FDG PET/CT performed prior to lymphoscintigraphy demonstrated a moderately FDG
      avid right inguinal lymph node that was indeterminate in nature. SPECT/CT
      revealed this lymph node to be a radioactive sentinel lymph node that was seen in
      the right groin on planar imaging. The patient then underwent right inguinal
      sentinel node sampling. Because pathologic study showed metastasis to the
      sentinel node, a planned pelvic exenteration was canceled, and the patient was
      referred for systemic treatment. Preoperative SPECT/CT lymphoscintigraphy is
      ideal for mapping the unpredicted lymphatic drainage pathways within the complex
      pelvic anatomy and this technique may also be used in the preoperative workup of
      other gynecologic malignancies.

PMID- 20139818
TI  - F-18 FDG PET/CT in the diagnosis of fever of unknown origin.
AB  - METHODS: The utility of Fluorine-18 fluorodeoxyglucose positron emission
      tomography/CT in identifying the causal source was assessed in this retrospective
      study. A total of 68 patients (33 men, 35 women; age range, 23-91 years) with
      fever of unknown origin (FUO) underwent a positron emission tomography/computed
      tomography (PET/CT) scan. PET/CT was considered helpful when abnormal results
      allowed an accurate diagnosis, based on histopathology, microbiologic assays, or
      clinical and imaging follow-up. RESULTS: PET/CT demonstrated suspected pathologic
      foci of Fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in 41 patients (60%), in
      38 of these 41 patients (93%) F-18 FDG PET/CT helped in identifying the causal
      source, including infection in 25 patients, inflammation in 11 patients, a benign
      neoplasm in 1 patient, and in 1 patient rejection of a pancreas transplant. In 27
      negative F-18 FDG PET/CT studies, no focal pathologic disease was diagnosed in
      the follow-up. In 6 of these 27 patients, a systemic disease without a focal
      manifestation was the cause for FUO. In the remaining 21 patients, fever and
      other signs subsided during follow-up. CONCLUSION: Overall 56% of the F-18 FDG
      PET/CT studies contributed in the identification of the source in patients with
      FUO, and elevated erythrocyte sedimentation rate and C-reactive protein (positive
      predictive value 93%). When systemic diseases are excluded F18-FDG PET/CT has a
      high negative predictive value for focal etiologies of FUO (negative predictive
      value 100%).

PMID- 20139819
TI  - Attenuation correction of somatostatin receptor SPECT by integrated low-dose CT:
      is there an impact on sensitivity?
AB  - AIM: Somatostatin receptor scintigraphy (SRS) is an established imaging modality
      for neuroendocrine tumors (NET). Additional single photon emission computed
      tomography (SPECT-CT) not only permits image fusion but also attenuation
      correction (AC) of SPECT data. This study evaluated whether attenuation corrected
      SPECT-images (SPECT[AC]) are more sensitive than nonattenuation corrected SPECT
      reconstructions (SPECT[NAC]) for the detection of NET lesions. METHODS: The
      imaging data (planar In-111-octreotide scintigraphy and SPECT-CT) of 50
      consecutive patients (28 male; 22 female; age, 34-80; mean, 65 years) with NET
      were included in this retrospective analysis. SPECT data were reconstructed with
      and without integrated CT-based AC and then analyzed by 2 experienced readers for
      the presence of pathologic uptake in a blinded consensus reading. Fused SPECT-CT,
      contemporary CT/MRI, and clinical as well as imaging follow-up served as a
      reference standard. All foci were rated in both the SPECT(NAC)- and SPECT(AC)
      reconstructions for intensity and contrast using a 6-point-score ("0 = no
      uptake/no delineation from surrounding tissue" to "5 = very high uptake/very
      strong delineation from surrounding tissue"). The scores were analyzed in a 6 x 6
      contingency table using the McNemar Bowker test. RESULTS: A total of 222
      pathologic foci were detected by SPECT(NAC) and 227 foci by SPECT(AC),
      respectively. In 67 of 227 foci (29.5%), focus intensity/contrast increased after
      AC, whereas only 5 foci showed a decrease (P < 0.001). Sensitivity increased by
      2.2% (P = 0.025; 95% CI: 0.02%-4.1%) as 5 foci were detected only by SPECT(AC).
      However, as these 3 patients were already diagnosed with systemic disease, there
      was no influence on the therapeutic strategy chosen. CONCLUSION: Attenuation
      correction of somatostatin receptor scintigraphy-SPECT significantly improves
      focus visualization and, albeit slightly, also significantly increases
      sensitivity.

PMID- 20139820
TI  - Dual time point C-11 acetate PET imaging can potentially distinguish focal
      nodular hyperplasia from primary hepatocellular carcinoma.
AB  - C-11 acetate positron emission tomography (PET) is known to have high sensitivity
      in detecting hepatocellular carcinoma. However, one of the shortcomings of C-11
      acetate PET in the diagnosis of hepatocellular carcinoma is that C-11 acetate
      also accumulates in focal nodular hyperplasia, which makes it challenging to
      distinguish hepatocellular carcinoma form focal nodular hyperplasia when a
      conventional single time point PET imaging method is used. Two patients with
      suspected hepatocellular carcinoma and negative fluoro-deoxy-glucose PET scans
      underwent C-11 acetate PET dual time imaging in which both early and delayed
      images were acquired. One patient was subsequently confirmed having
      hepatocellular carcinoma while the other had focal nodular hyperplasia. C-11
      acetate imaging was positive in both patients. Interestingly, in hepatocellular
      carcinoma the C-11 acetate activity in the delayed images is higher than in the
      early images while in focal nodular hyperplasia, the C-11 acetate activity
      decreased in the delayed image when compared with early images. Our findings
      suggest that dual time point imaging has potential to improve the diagnostic
      accuracy of C-11 acetate PET in the diagnosis of hepatocellular carcinoma.

PMID- 20139822
TI  - Thyroid hemiagenesis and Graves' disease in a child.
AB  - Hemiagenesis of the thyroid is a rare malformation and Graves' disease with
      ophthalmopathy is reported quite rarely in adult patients but is not seen in
      children. This is a report of an 8-year-old girl with congenital absence of the
      left thyroid lobe, or hemiagenesis.

PMID- 20139821
TI  - Comparative evaluation of F-18 FDOPA, F-18 FDG, and F-18 FLT-PET/CT for metabolic
      imaging of low grade gliomas.
AB  - INTRODUCTION: We undertook this prospective study to compare amino acid
      metabolism, glucose metabolism, and proliferation in primary and recurrent low
      grade gliomas using positron emission tomography (PET)/computed tomography with F
      18 FDOPA, F-18 FDG, and F-18 FLT. METHODS: Fifteen patients with newly diagnosed
      or previously treated low grade gliomas (WHO grade I or II) were subjected to F
      18-FDOPA, F-18 FDG, and F-18 FLT PET/computed tomography studies on consecutive
      days. This included 2 patients in remission as control subjects. Uptake of all
      the 3 tracers were analyzed visually and quantified using standardized uptake
      values and tumor to normal (T/N) ratios. The accuracy of all the 3 PET tracers in
      the detection of newly diagnosed and recurrent low grade gliomas was compared.
      RESULTS: F-18 FDOPA was positive in all cases of primary and recurrent low grade
      gliomas and negative in the patients in remission. Tumor was visualized on F-18
      FDG in 7 of 13 cases, F-18-FLT was positive in 4 of 13 cases. Average tumor
      standardized uptake values max for F-18 FDOPA (5.75 +/- 4.9) and F-18 FLT (1.8 +/
      0.91) was lower than that of F-18 FDG (8.5 +/- 4.4). T/N ratios for F-18-FDOPA
      (2.3 +/- 0.51) and F-18 FLT (1.8 +/- 0.91) were higher than F-18 FDG (1.03 +/-
      0.64) providing good image contrast for tumor detection in positive cases.
      CONCLUSION: F-18 FDOPA scan is superior to both F-18 FLT and F-18 FDG for
      visualization of primary and recurrent low grade gliomas. F-18-FLT should not be
      considered for evaluation of recurrent low grade gliomas.

PMID- 20139823
TI  - F-18 FDG PET/CT characterization of talc pleurodesis-induced pleural changes over
      time: a retrospective study.
AB  - PURPOSE: The current study characterized pleural changes induced by talc
      pleurodesis (TP), based on serial positron emission tomography/computer
      tomography (PET/CT) with F-18 fluorodeoxyglucose (FDG). MATERIALS AND METHODS: A
      total of 8 cancer patients who had both TP and PET/CT and no evidence of active
      pleural involvement after TP were retrospectively evaluated. Maximum standard
      uptake values, maximum Hounsfield units (HU), and thickness were followed over
      time. RESULTS: The 8 patients had 25 PET/CT scans performed in an average of 22
      months after TP. An increased FDG uptake was associated with an increase in
      pleural thickness within 5 months after TP, and both parameters showed
      statistical significance as compared with findings before TP. After 5 months of
      TP, the standard uptake value appeared to persist or increase further, and the
      pleural thickening stabilized. The formation of calcification was a slow process
      and might lag behind the changes in FDG metabolism and pleural thickness. The HU
      did not change significantly once pleural calcification had been formed.
      CONCLUSIONS: Knowledge of aforementioned pleural changes may help differentiate
      TP induced pleural inflammation from pleural malignancy and to avoid false
      positive interpretation of FDG PET/CT exams.

PMID- 20139824
TI  - Epstein-Barr virus mimicking lymphoma on FDG-PET/CT.
AB  - We report the case of a 17-year-old girl who presented with a several month
      history of fevers and abdominal pain. After cytomegalovirus (CMV) and Epstein
      Barr virus (EBV) titers returned normal, FDG-PET/CT was obtained due to concern
      for lymphoma. FDG-PET/CT revealed a pattern of hypermetabolic activity in the
      adenoids, bilateral cervical lymph nodes, abdominal lymph nodes, and spleen,
      highly concerning for lymphoma. However, subsequent biopsy of a cervical lymph
      node revealed lymphadenitis consistent with EBV. This case highlights infection
      as the most well-known false-positive cause on FDG-PET, and how biopsy is
      essential to definitively distinguish malignancy from infection.

PMID- 20139825
TI  - Cutaneous graft-versus-host disease on Tc-99m leukocyte scintigraphy.

PMID- 20139826
TI  - Multi-level lumbar Baastrup disease on F-18 FDG PET-CT.

PMID- 20139827
TI  - Radiography, bone scintigraphy, SPECT/CT and MRI of fibrous dysplasia of the
      third lumbar vertebra.

PMID- 20139828
TI  - Role of labeled white cell scintigraphy with SPECT/CT in Crohn disease.

PMID- 20139829
TI  - FDG PET-CT findings in epiploic appendagitis.

PMID- 20139830
TI  - Reperfusion injury to skeletal muscle on bone scan.

PMID- 20139831
TI  - Scintigraphic findings of growing herniation pits of the femoral neck during
      serial follow-up studies.

PMID- 20139832
TI  - Aggressive noonan-like multiple giant cell lesion syndrome on Tc-99m MDP bone
      scan.

PMID- 20139833
TI  - Shoulder pain in a young break-dancer evaluated with bone scintigraphy.

PMID- 20139834
TI  - Abnormal F-18 FDG uptake in two epidermoid cysts on PET/CT.

PMID- 20139835
TI  - Tc-99m hynic octreotide SPECT-MRI in brain metastasis of thyroid papillary
      insular cancer.

PMID- 20139836
TI  - An unusual case of synchronous renal cell carcinoma in a horseshoe kidney and
      intrahepatic cholangiocarcinoma.

PMID- 20139837
TI  - Incidental detection of renal transplantation urinary leakage on FDG-PET/CT
      imaging for evaluation of lung metastases.

PMID- 20139838
TI  - FDG avid patchy bone marrow misinterpreted as melanoma metastases to bone in a
      case of aplastic anemia.

PMID- 20139839
TI  - Cerebral blood flow on ECD SPECT in a patient with adult onset Alexander disease.

PMID- 20139840
TI  - Detection of metastases to internal jugular vein and superior vena cava on 131-I
      scan.

PMID- 20139841
TI  - Lymphoma of the superior vena cava detected with FDG PET/CT.

PMID- 20139842
TI  - Detection of a mammographically occult invasive lobular breast carcinoma by
      PET/CT in a patient with lymphoma.

PMID- 20139843
TI  - Unilateral pulmonary oligemia detected on blood pool images from a Tc-99m MDP
      bone scan.

PMID- 20139844
TI  - Thallium-201 scintigraphy of myxofibrosarcoma.

PMID- 20139845
TI  - Cervical tuberculous lymphadenitis mimicking distant lymph node metastasis on F
      18 FDG PET/CT in a patient with gastric carcinoid tumor.

PMID- 20139846
TI  - A case of malignant melanoma with cardiac and gallbladder metastases detected by
      FDG PET-CT.

PMID- 20139847
TI  - Elevated FDG activity in the spinal cord and the sciatic nerves due to
      neuropathy.

PMID- 20139848
TI  - Encephalitis depicted by a combination of C-11 acetate and F-18 FDG PET/CT.

PMID- 20139850
TI  - Portosystemic collateral circulation: demonstrated by Tc-99m-RBC SPECT/CT.

PMID- 20139849
TI  - In-111 DTPA ommaya cisternography with delayed radiotracer activity demonstrated
      in the peritoneal cavity.

PMID- 20139851
TI  - Lack of splenic uptake of In-111 pentetreotide due to splenic embolization.

PMID- 20139852
TI  - Synchronous prostate cancer incidentally detected by FDG-PET/CT in staging a
      patient with newly diagnosed nasopharyngeal cancer.

PMID- 20139854
TI  - Left maxillary sinus malignant fibrous histiocytoma on FDG PET-CT.

PMID- 20139853
TI  - Identifying Ga-67 uptake in brown adipose tissue with SPECT/CT.

PMID- 20139855
TI  - Current readings in nuclear medicine.

PMID- 20139856
TI  - A pilot study comparing hydrocortisone premedication to concomitant azathioprine
      treatment in preventing loss of response to infliximab.
AB  - OBJECTIVES: Antibodies to infliximab may lead to loss of response to infliximab
      (IFX) in Crohn's disease. Azathioprine (AZA) coadministration prevents the
      formation, whereas hydrocortisone (HC) premedication reduces the levels of
      antibodies to IFX. This pilot study aims at assessing the efficacy of these
      strategies to prevent loss of response to IFX. METHODS: Eligible patients had
      active steroid-dependent luminal Crohn's disease and received IFX (5 mg/kg at
      weeks 0, 2, and 6 for induction and then scheduled q8 week for remission
      maintenance). Patients were stratified in a 1 : 1 ratio to oral AZA (2-2.5
      mg/kg/day, stratum A) or HC premedication (250 mg intravenously, stratum B).
      Stratum A included only patients naive to AZA; stratum B included both AZA naive
      and intolerant patients. Steroids were tapered within 6-8 weeks. Patients were
      followed up with monthly clinical assessments, laboratory tests, Crohn's Disease
      Activity Index calculations, adverse-events check up, and adherence to treatment.
      RESULTS: Overall, 23 patients received IFX/HC and 23 IFX/AZA. There were no
      differences at baseline in any patient-related or disease-related parameters.
      Seventeen (74%) patients on IFX/AZA completed the study; six patients were
      withdrawn for primary nonresponse (one patient), lost response to IFX (two
      patients), or AZA-related adverse events. Eighteen (78%) patients on IFX/HC
      completed the study; five patients were withdrawn for primary nonresponse (one
      patient), loss of response (two patients), or infusion reactions to IFX. No
      significant differences emerged between strata in clinical remission rates or
      lost response to IFX. CONCLUSION: This prospective 2-year pilot study has not
      confirmed superiority of any available strategy to maintain the efficacy of IFX.

PMID- 20139864
TI  - Depletion of specific cell populations by complement depletion.
AB  - The purification of immune cell populations is often required in order to study
      their unique functions. In particular, molecular approaches such as real-time PCR
      and microarray analysis require the isolation of cell populations with high
      purity. Commonly used purification strategies include fluorescent activated cell
      sorting (FACS), magnetic bead separation and complement depletion. Of the three
      strategies, complement depletion offers the advantages of being fast,
      inexpensive, gentle on the cells and a high cell yield. The complement system is
      composed of a large number of plasma proteins that when activated initiate a
      proteolytic cascade culminating in the formation of a membrane-attack complex
      that forms a pore on a cell surface resulting in cell death(1). The classical
      pathway is activated by IgM and IgG antibodies and was first described as a
      mechanism for killing bacteria. With the generation of monoclonal antibodies
      (mAb), the complement cascade can be used to lyse any cell population in an
      antigen-specific manner. Depletion of cells by the complement cascade is achieved
      by the addition of complement fixing antigen-specific antibodies and rabbit
      complement to the starting cell population. The cells are incubated for one hour
      at 37 degrees C and the lysed cells are subsequently removed by two rounds of
      washing. MAb with a high efficiency for complement fixation typically deplete 95
      100% of the targeted cell population. Depending on the purification strategy for
      the targeted cell population, complement depletion can be used for cell
      purification or for the enrichment of cell populations that then can be further
      purified by a subsequent method.

PMID- 20139865
TI  - Ophiosetin, a new tetramic acid derivative from the mycopathogenic fungus
      Elaphocordyceps ophioglossoides.

PMID- 20139866
TI  - Two novel nucleosidyl-peptide antibiotics: Sansanmycin F and G produced by
      Streptomyces sp SS.

PMID- 20139867
TI  - Anti-leishmanial activity of betulin derivatives.
AB  - Leishmanicidal activity of 24 derivatives of naturally occurring and abundant
      triterpenes belonging to the lupane series, betulin, betulinic acid and betulonic
      acid, is described in this study. The easily modified positions of the lupane
      skeleton, the hydroxy groups of C-3 and C-28, as well as the carbon-carbon double
      bond C-20-C-29 were used as a starting point to prepare a library of triterpenoid
      derivatives for bioactivity studies. The compounds were evaluated against
      Leishmania donovani axenic amastigotes on a microplate assay at 50 microM. GI(50)
      values of the most effective compounds were evaluated, as well as their
      cytotoxicity on the human macrophage cell line THP-1, and anti-leishmanial
      activity against L. donovani-infected THP-1 macrophages was determined. Betulonic
      acid was the most potent derivative, yielding a GI(50) value of 14.6 microM.
      Promising and distinct structure-activity relationships were observed, and these
      compounds can be regarded as significant lead molecules for further improvement
      and optimization.

PMID- 20139869
TI  - Mid-level providers in gastroenterology.
AB  - One response to the challenges of modern day clinical practice has been to employ
      "mid-level providers" (MLPs), such as physician assistants and nurse
      practitioners. MLPs may complement physicians by supporting patient self
      management and performing routine, protocol-guided management. In turn, MLPs may
      improve health outcomes and simultaneously lower costs. Within gastroenterology,
      the prevalence of MLPs remains unknown, though it appears to be significant and
      increasing. Additionally, professional organizations predict that in the future,
      MLPs will play a central role in digestive disease care. Although incorporating
      MLPs into gastroenterology has great potential, numerous challenges exist, and
      their specific roles must first be defined and evaluated.

PMID- 20139870
TI  - Incorporating quality measurement and improvement into a gastroenterology
      practice.

PMID- 20139871
TI  - Fuzzy diagnoses.

PMID- 20139874
TI  - Beta-defensins and Crohn's disease: confusion from counting copies.
AB  - Recent research has suggested that a family of antimicrobial and inflammatory
      molecules, called beta-defensins, are involved in the etiology of Crohn's
      disease. In this issue, Bentley and colleagues provide data that disagree with
      previous studies. They show that the beta-defensins that are copy number
      polymorphic have, on average, higher genomic copy number in patients when
      compared with healthy controls. This editorial places these new data in the
      context of previous research on the genetics of beta-defensin copy number
      polymorphism and association with Crohn's disease. It also suggests a path
      allowing this research area to move forward with confidence.

PMID- 20139877
TI  - The difficulty in predicting outcome in acute pancreatitis.
AB  - Current methods to predict the development of severe pancreatitis are complex,
      cumbersome, and inaccurate. Simpler scoring systems like the one studied in this
      issue of the Journal are an improvement in simplicity but not in accuracy. More
      sophisticated approaches are needed for more accurate prediction, which would
      allow improved triage and management of these patients.

PMID- 20139878
TI  - PPIs may not predispose to eosinophilic esophagitis.

PMID- 20139879
TI  - Re: Might the use of acid-suppressive medications predispose to the development
      of eosinophilic esophagitis?

PMID- 20139881
TI  - A paradigm shift is required to facilitate recognition of iron deficiency.

PMID- 20139882
TI  - A confusing relationship between Child-Turcotte-Pugh class A and compensated
      cirrhosis.

PMID- 20139885
TI  - Campylobacter infection in patients with ileal pouches.

PMID- 20139886
TI  - Is preterm delivery in inflammatory bowel disease women part of the burden of
      innate immunity deficiency?

PMID- 20139887
TI  - Retinal detachment as a presenting feature of metastatic esophageal
      adenocarcinoma.

PMID- 20139888
TI  - Sodium phosphate tablets and acute phosphate nephropathy: how much hydration is
      "adequate"?

PMID- 20139892
TI  - The disruption of the rod-derived cone viability gene leads to photoreceptor
      dysfunction and susceptibility to oxidative stress.
AB  - Rod-derived cone viability factor (RdCVF) is a thioredoxin-like protein, which
      has therapeutic potential for rod-cone dystrophies such as retinitis pigmentosa
      (RP). Cone loss in rodent models of RP is effectively reduced by RdCVF treatment.
      In this study, we investigate the physiological role of RdCVF in the retina by
      analyzing the phenotype of the mouse lacking the RdCVF gene, Nxnl1. Although the
      mice do not show an obvious developmental defect, an age-related reduction of
      both cone and rod function and a delay in the dark-adaptation of the retina are
      recorded by electroretinogram (ERG). This functional change is accompanied by a
      17% reduction in cone density and a 20% reduction in thickness of the outer
      nuclear layer. The transcriptome of the retina reveals early changes in the
      expression of genes involved in programmed cell death, stress-response and redox
      signaling, which is followed by a generalized injury response with increased
      microglial activation, GFAP, FGF2 and lipid peroxidation levels. Furthermore,
      cones of the mice lacking Nxnl1 are more sensitive to oxidative stress with a
      reduction of 65% in the cone flicker ERG amplitude measured under hyperoxic
      conditions. We show here that the RdCVF gene, in addition to therapeutic
      properties, has an essential role in photoreceptor maintenance and resistance to
      retinal oxidative stress.

PMID- 20139893
TI  - Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem
      like characteristics in a hypoxic environment.
AB  - Abl tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are
      ineffective against Bcr-Abl(+) leukemic stem cells. Thus, the identification of
      novel agents that are effective in eradicating quiescent Bcr-Abl(+) stem cells is
      needed to cure leukemias caused by Bcr-Abl(+) cells. Human Bcr-Abl(+) cells
      engrafted in the bone marrow of immunodeficient mice survive under severe
      hypoxia. We generated two hypoxia-adapted (HA)-Bcr-Abl(+) sublines by selection
      in long-term hypoxic cultures (1.0% O(2)). Interestingly, HA-Bcr-Abl(+) cells
      exhibited stem cell-like characteristics, including more cells in a dormant,
      increase of side population fraction, higher beta-catenin expression, resistance
      to Abl TKIs, and a higher transplantation efficiency. Compared with the
      respective parental cells, HA-Bcr-Abl(+) cells had higher levels of protein and
      higher enzyme activity of glyoxalase-I (Glo-I), an enzyme that detoxifies
      methylglyoxal, a cytotoxic by-product of glycolysis. In contrast to Abl TKIs, Glo
      I inhibitors were much more effective in killing HA-Bcr-Abl(+) cells both in
      vitro and in vivo. These findings indicate that Glo-I is a novel molecular target
      for treatment of Bcr-Abl(+) leukemias, and, in particular, Abl TKI-resistant
      quiescent Bcr-Abl(+) leukemic cells that have acquired stem-like characteristics
      in the process of adapting to a hypoxic environment.

PMID- 20139894
TI  - Granzymes in age-related cardiovascular and pulmonary diseases.
AB  - Chronic inflammation is a hallmark of age-related cardiovascular and pulmonary
      diseases. Granzymes are a family of serine proteases that have been traditionally
      viewed as initiators of immune-mediated cell death. However, recent findings
      suggest that the pathophysiological role of granzymes is complex. Emerging
      functions for granzymes in extracellular matrix degradation, autoimmunity, and
      inflammation suggests a multifactorial mechanism by which these enzymes are
      capable of mediating tissue damage. Recent discoveries showing that granzymes can
      be produced and secreted by nonimmune cells during disease provide an additional
      layer of intricacy. This review examines the emerging biochemical and clinical
      evidence pertaining to intracellular and/or extracellular granzymes in the
      pathogenesis of aging and cardiopulmonary diseases.

PMID- 20139895
TI  - TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate
      1.
AB  - Lipid rafts have been known to be platforms to initiate cellular signal
      transduction of insulin-like growth factor (IGF) inducing skeletal muscle
      differentiation and hypertrophy. Here, tripartite motif 72 (TRIM72), with a
      really interesting new gene (RING)-finger domain, a B-box, two coiled-coil
      domains, and a SPRY (SPla and RYanodine receptor) domain, was revealed to be
      predominantly expressed in the sarcolemma lipid rafts of skeletal and cardiac
      muscles. Adenoviral TRIM72 overexpression prevented but RNAi-mediated TRIM72
      silencing enhanced C2C12 myogenesis by modulating the IGF-induced insulin
      receptor substrate-1 (IRS-1) activation through the molecular association of
      TRIM72 with IRS-1. Furthermore, myogenic activity was highly enhanced with
      increased IGF-induced Akt activation in the satellite cells of TRIM72(-/-) mice,
      compared to those of TRIM72+/+ mice. Because TRIM72 promoter analysis shows that
      two proximal E-boxes in TRIM72 promoter were essential for MyoD- and Akt
      dependent TRIM72 transcription, we can conclude that TRIM72 is a novel antagonist
      of IRS-1, and is essential as a negative regulator of IGF-induced muscle
      differentiation.

PMID- 20139896
TI  - Baicalin attenuates oxygen-glucose deprivation-induced injury by inhibiting
      oxidative stress-mediated 5-lipoxygenase activation in PC12 cells.
AB  - AIM: To determine whether the flavonoid baicalin attenuates oxygen-glucose
      deprivation (OGD)-induced injury by inhibiting oxidative stress-mediated 5
      lipoxygenase (5-LOX) activation in PC12 cells. METHODS: The effects of baicalin
      and the 5-LOX inhibitor zileuton on the changes induced by OGD/recovery or
      H(2)O(2) (an exogenous reactive oxygen species [ROS]) in green fluorescent
      protein-5-LOX-transfected PC12 cells were compared. RESULTS: Both baicalin and
      zileuton attenuated OGD/recovery- and H(2)O(2)-induced injury and inhibited
      OGD/recovery-induced production of 5-LOX metabolites (cysteinyl leukotrienes) in
      a concentration-dependent manner. However, baicalin did not reduce baseline
      cysteinyl leukotriene levels. Baicalin also reduced OGD/recovery-induced ROS
      production and inhibited 5-LOX translocation to the nuclear envelope and p38
      phosphorylation induced by OGD/recovery and H(2)O(2). In contrast, zileuton did
      not show these effects. CONCLUSION: Baicalin can inhibit 5-LOX activation after
      ischemic injury, which may partly result from inhibition of the ROS/p38 mitogen
      activated protein kinase pathway.

PMID- 20139897
TI  - Repurposing an old drug for a new use: glybenclamide exerts antiplatelet activity
      by interacting with the thromboxane A(2) receptor.
AB  - AIM: To investigate the potential antagonistic activity of the antidiabetic agent
      glybenclamide for the human platelet thromboxane A(2) receptor (abbreviated as
      TPR). METHODS: Platelets were obtained from healthy donors. Aggregation studies
      were performed in a model 700 aggregometry system. Radioactivity was counted in a
      Beckman LS 6000 liquid scintillation counter and calcium imaging was performed
      using an LS50B PerkinElmer Fluorescence Spectrometer. RESULTS: It was found that
      glybenclamide: 1) inhibited aggregation induced by the TPR agonist U46619
      (IC(50)=2.3+/-0.31 micromol/L) and by the thromboxane A(2) precursor arachidonic
      acid (IC(50)=2.6+/-0.24 micromol/L); 2) displaced SQ29,548 from its binding sites
      on platelets; 3) lacked any detectable effects on aggregation stimulated by ADP,
      or the thrombin receptor activating-peptide 4; 4) blocked calcium mobilization
      induced by U46619, but not by ADP; and 5) failed to raise cAMP levels.
      CONCLUSION: The findings indicate that glybenclamide exerts inhibitory effects on
      platelets by interacting with TPR. Thus, glybenclamide or a rationally designed
      derivative has the potential to serve as an antithrombotic agent.

PMID- 20139898
TI  - Hydrogen peroxide stress stimulates phosphorylation of FoxO1 in rat aortic
      endothelial cells.
AB  - AIM: To examine whether the phosphorylation of the O subfamily of forkhead
      transcription factors (FoxO) is involved in response to oxidative stress in rat
      aortic endothelial cells (RAECs). METHODS: RAECs were treated with H(2)0(2) and
      phosphorylation status of proteins were evaluated by Western blot analysis. The
      subcellular localization of FoxO1 was determined by nuclear and cytosolic
      fractionation followed by Western blot analysis as well as immunocytochemistry.
      The transcriptional activity of FoxO1 in H(2)0(2) stress was assessed by
      luciferase reporter assay. Expression of FoxO1 target gene was determined by real
      time PCR analysis. RESULTS: H(2)0(2) stress stimulated phosphorylation of FoxO1
      at Thr24 and Ser256 in a concentration and time dependent manner in RAECs.
      Pretreatment of RAECs with PI-3K inhibitors abolished the activation of Akt and
      prevented the phosphorylation of FoxO1. Akt-mediated phosphorylation promoted
      nuclear exclusion of FoxO1. An IRS-driven luciferase activity transactivated by
      exogenous FoxO1 was modestly suppressed by hydrogen peroxide stress. The
      expression of Bim, a target gene of FoxO factors, was negatively regulated by Akt
      mediated phosphorylation in response to hydrogen peroxide stimulation.
      CONCLUSION: Our data demonstrate that phosphorylation of FoxO1 by PI-3K/Akt
      signaling is implicated in response to oxidative stress in vascular endothelial
      cells.

PMID- 20139899
TI  - CPU86017, a berberine derivative, attenuates cardiac failure through normalizing
      calcium leakage and downregulated phospholamban and exerting antioxidant
      activity.
AB  - AIM: To investigate whether CPU86017, a berberine derivative, attenuates heart
      failure by blocking calcium influx and exerting its antioxidant activity.
      METHODS: Myocardial infarction was induced in male Sprague-Dawley rats for 17 d
      followed by isoproterenol (ISO) (5 mg/kg, sc) treatment for 5 d to reduce cardiac
      function. The rats were divided into 5 groups: sham operation, myocardial
      infarction (MI), MI plus ISO, and co-treated (in mg/kg, po) with either
      propranolol (PRO, 10) or CPU86017 (80). Hemodynamic measurements were conducted,
      and measurements of the redox system, calcium handling proteins and endothelin
      (ET) system in vivo were done. Furthermore, calcium flux studies and PLB
      immunocytochemistry were conducted in vitro. RESULTS: Compared to sham operation,
      HF was evident following MI and further worsened by ISO treatment. This occurred
      in parallel with downregulated mRNA and protein production of SERCA2a, PLB, and
      FKBP12.6, and was associated with upregulation of preproET-1, endothelin
      converting enzyme, and PKA mRNA production in the myocardium in vivo. Calcium
      leakage was induced by ISO treatment of isolated beating myocytes in vitro. These
      changes were attenuated by treatment with either PRO or CPU86017. PLB
      fluorescence in myocytes was downregulated by ISO treatment, and was relieved
      significantly by treatment with antioxidant aminoguanidine, ascorbic acid or
      CPU86017 in vitro. CONCLUSION: HF, calcium leakage, downregulated PLB, FKBP12.6,
      SERCA2a production, and upregulated PKA were caused by ISO treatment, and were
      abolished by CPU86017 treatment. The beneficial effects of CPU86017 are
      attributable to its antioxidant and calcium influx blocking effects.

PMID- 20139900
TI  - Protective role of PI3-kinase/Akt/eNOS signaling in mechanical stress through
      inhibition of p38 mitogen-activated protein kinase in mouse lung.
AB  - AIM: To test the hypothesis that PI3K/Akt/eNOS signaling has a protective role in
      a murine model of ventilation associated lung injury (VALI) through down
      regulation of p38 MAPK signaling. METHODS: Male C57BL/J6 (wild-type, WT) or eNOS
      knockout mice (eNOS(-/-)) were exposed to mechanical ventilation (MV) with low
      (LV(T), 7 mL/kg) and high tidal volume (HV(T), 20 mL/kg) for 0-4 h. A subset of
      WT mice was administered the specific inhibitors of PI3K (100 nmol/L Wortmannin
      [Wort], ip) or of p38 MAPK (SB203580, 2 mg/kg, ip) 1 h before MV. Cultured type
      II alveolar epithelial cells C10 were exposed to 18% cyclic stretch for 2 h with
      or without 20 nmol/L Wort pretreatment. At the end of the experiment, the
      capillary leakage in vivo was assessed by extravasation of Evans blue dye (EBD),
      wet/dry weight ratio and lung lavage protein concentration. The lung tissue and
      cell lysate were also collected for protein and histological review. RESULTS: MV
      decreased PI3K/Akt phosphorylation and eNOS expression but increased phospho-p38
      MAPK expression along with a lung leakage of EBD. Inhibitions of phospho-Akt by
      Wort worsen the lung edema, whereas inhibition of p38 MAPK kinase restored
      activation of Akt together with alleviated capillary leakage. eNOS(-/-) mice
      showed an exacerbated lung edema and injury. The stretched C10 cells demonstrated
      that Wort diminished the activation of Akt, but potentiated phosphorylation of
      MAPK p38. CONCLUSION: Our results indicate that PI-3K/Akt/eNOS pathway has
      significant protective effects in VALI by preventing capillary leakage, and that
      there is a cross-talk between PI3K/Akt and p38 MAPK pathways in vascular barrier
      dysfunction resulting from VALI.

PMID- 20139901
TI  - SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in
      Chinese type 2 diabetics treated with metformin.
AB  - AIM: To investigate the potential relationship between the SLC22A2 gene
      polymorphism and blood lactate concentration in Shanghai Hans suffering from type
      2 diabetes mellitus (T2DM). METHODS: The SLC22A2 single nucleotide polymorphism
      (SNP) 808G/T was genotyped in 400 T2DM patients, including a metformin-treated
      group (n=200) and a non-metformin-treated group (n=200). Fasting plasma lactic
      acid levels were measured with an enzyme-electrode assay. Biochemical indexes,
      including plasma alanine aminotransferase (ALT), creatinine (Cr), and glycolated
      hemoglobin (HbA1c), were also measured. RESULTS: The fasting plasma lactate
      concentration in the metformin-treated group was significantly higher than that
      in the non-metformin-treated group (1.29+/-0.45 mmol/L vs 1.18+/-0.44 mmol/L,
      P=0.015). Additionally, the ratio of patients with hyperlactacidemia was 8%
      (16/200) for the metformin-treated group and 5.5% (11/200) for the non-metformin
      treated group, with no lactic acidosis found in either group. The frequency of
      the SLC22A2 808G/T T allele was 12.9%. Patients with the mutant genotype (TT) had
      a higher blood lactate concentration in the metformin-treated group than those in
      the non-metformin-treated group (t=2.492, P=0.013). This trend was not observed
      in the GG and GT genotypes when compared with metformin-treated and non-metformin
      treated groups. Patients with the mutant genotype (TT) in the metformin-treated
      group also had a higher incidence of hyperlactacidemia compared with the GG
      genotype (40.0% vs 6.9%, P=0.050) in the metformin-treated group and the GG
      (6.0%, P=0.042) or GT (4.3%, P=0.043) genotypes in the non-metformin-treated
      group. In the metformin-treated group, there were significant gender differences
      in lactate concentrations in the TT (2.18+/-0.15 vs 1.04+/-0.27 mmol/L, P=0.008)
      and GG genotypes (1.40+/-0.51 vs 1.19+/-0.35 mmol/L, P=0.004). The lactate levels
      of women with the TT genotype were the highest in the metformin-treated group,
      but differences in lactate levels among the genotypes were not observed in the
      non-metformin-treated group. CONCLUSION: There is an 808G/T polymorphism in the
      SLC22A2 gene in Chinese Hans with T2DM. The 808G>T variance in the SLC22A2 gene
      can affect the plasma lactate level and the incidence of hyperlactacidemia in
      T2DM patients undergoing metformin therapy. Additionally, the female patients
      carrying the TT genotype are prone to lactatemia.

PMID- 20139902
TI  - Immunomodulatory activity of andrographolide on macrophage activation and
      specific antibody response.
AB  - AIM: To investigate the immunomodulatory effects of andrographolide on both
      innate and adaptive immune responses. METHODS: Andrographolide (10 microg/mL in
      vitro or 1 mg/kg in vivo) was used to modulate LPS-induced classical activated
      (M1) or IL-4-induced alternative activated (M2) macrophages in vitro and humor
      immune response to HBsAg in vivo. Cytokine gene expression profile (M1 vs M2) was
      measured by real-time PCR, IL-12/IL-10 level was detected by ELISA, and surface
      antigen expression was evaluated by flow cytometry, whereas phosphorylation level
      of ERK 1/2 and AKT was determined by Western blot. The level of anti-HBs
      antibodies in HBsAg immunized mice was detected by ELISA, and the number of HBsAg
      specific IL-4-producing splenocyte was enumerated by ELISPOT. RESULTS:
      Andrographolide treatment in vitro attenuated either LPS or IL-4 induced
      macrophage activation, inhibited both M1 and M2 cytokines expression and
      decreased IL-12/IL-10 ratio (the ratio of M1/M2 polarization). Andrographolide
      down-regulated the expression of mannose receptor (CD206) in IL-4 induced
      macrophages and major histocompability complex/costimulatory molecules (MHC I,
      CD40, CD80, CD86) in LPS-induced macrophages. Correspondingly, anti-HBs antibody
      production and the number of IL-4-producing splenocytes were reduced by in vivo
      administration of andrographolide. Reduced phosphorylation levels of ERK1/2 and
      AKT were observed in macrophages treated with andrographolide. CONCLUSION:
      Andrographolide can modulate the innate and adaptive immune responses by
      regulating macrophage phenotypic polarization and Ag-specific antibody
      production. MAPK and PI3K signaling pathways may participate in the mechanisms of
      andrographolide regulating macrophage activation and polarization.

PMID- 20139903
TI  - Downregulation of Dickkopf-1 is responsible for high proliferation of breast
      cancer cells via losing control of Wnt/beta-catenin signaling.
AB  - AIM: To investigate the role of DKK-1/Wnt/beta-catenin signaling in high
      proliferation of LM-MCF-7 breast cancer cells, a sub-clone of MCF-7 cell line.
      METHODS: Two cell lines (MCF-7 and LM-MCF-7) with different proliferation
      abilities were used. LM-MCF-7 cells were transiently transfected with the pcDNA3
      DKK-1 plasmid encoding the DKK-1 gene (or MCF-7 cells were transfected siRNA
      targeting DKK-1 mRNA). Flow cytometry analysis and 5-bromo-2'-deoxyuridine (BrdU)
      incorporation assay were applied to detect the cell proliferation. The expression
      levels of beta-catenin, phosphorylated beta-catenin, c-Myc, cyclin D1 and
      Survivin were examined by Western blot analysis. The regulation of Survivin was
      investigated by Luciferase reporter gene assay. RESULTS: Western blot and RT-PCR
      analysis showed that the expression level of DKK-1 was downregulated in LM-MCF-7
      relative to MCF-7 cells. Flow cytometry and BrdU incorporation assay showed DKK-1
      could suppress growth of breast cancer cells. Overexpression of DKK-1 was able to
      accelerate phosphorylation-dependent degradation of beta-catenin and downregulate
      the expression of beta-catenin, c-Myc, cyclin D1 and Survivin. Luciferase
      reporter gene assay demonstrated that Survivin could be regulated by beta
      catenin/TCF4 pathway. CONCLUSION: We conclude that the downregulation of DKK-1 is
      responsible for the high proliferation ability of LM-MCF-7 breast cancer cells
      via losing control of Wnt/beta-catenin signaling pathway, in which c-Myc,
      cyclinD1 and Survivin serve as essential downstream effectors. Our finding
      provides a new insight into the mechanism of breast cancer cell proliferation.

PMID- 20139904
TI  - The epoxyeicosatrienoic acid-stimulated phosphorylation of EGF-R involves the
      activation of metalloproteinases and the release of HB-EGF in cancer cells.
AB  - AIM: To test the hypothesis that the epoxyeicosatrienoic acid (EET)-induced
      transactivation of EGF-R depends on the activation of metalloproteinases and the
      subsequent release of HB-EGF in cancer cells. METHODS: Exogenous 14,15-EET were
      added to four human-derived cancer cell lines Tca-8113, A549, HepG2, and MDA-MB
      231, or these same cell lines were transfected with a mutant CYP epoxygenase
      (CYP102 F87V, an active 14,15-epoxygenase). The effects of elevated EET levels on
      the phosphorylation of tyrosine residues in the EGF receptor and on ERK1/2
      activation were then assessed. RESULTS: Both the addition of 14,15-EET and the
      transfection of cells with CYP102 F87V markedly increased the phosphorylation of
      the tyrosine residues of EGF-R and ERK1/2, an effect that was blocked by a
      selective EGF-R tyrosine kinase inhibitor (tyrphostin AG1478), a broad-spectrum
      metalloproteinase inhibitor (1,10-phenanthroline), and an inhibitor of HB-EGF
      release (CRM197) in Tca-8113 cells. In addition, AG1478, 1,10-phenanthroline, and
      CRM197 also inhibited the tyrosine phosphorylation of EGF-R and ERK1/2 that was
      induced by 14,15-EET in the A549, HepG2, and MDA-MB-231 cell lines. CONCLUSION:
      These results suggest that the EET-induced transactivation of EGF-R depends on
      activation of metalloproteinases and the subsequent release of HB-EGF in cancer
      cell lines.

PMID- 20139905
TI  - Bicyclol protects HepG2 cells against D-galactosamine-induced apoptosis through
      inducing heat shock protein 27 and mitochondria associated pathway.
AB  - AIM: To study the inducing effect of bicyclol on heat shock protein 27 (HSP27)
      and its role on anti-apoptosis in HepG2 cells intoxicated with D-galactosamine (D
      GaIN). METHODS: HepG2 cells were treated with various concentrations of bicyclol
      and then subjected to D-GaIN intoxication. Apoptosis was assayed by hoechst 33258
      staining and flow cytometry analysis. HSP27, cytochrome c, apoptosis inducing
      factor (AIF) and c-Jun N-terminal kinase (JNK) were assayed by Western blot. Heat
      shock factor 1 (HSF1) was determined by electrophoretic mobility shift assay and
      the interactions of HSP27 with cytochrome c and AIF were detected by co
      immunoprecipitation. RESULTS: The results showed that bicyclol induced HSP27
      protein and mRNA expression in HepG2 cells in both time- and dose-dependent
      manners (the maximal response: 1.23 fold increase at 100 micromol/L). Bicyclol
      treatment stimulated HSF1 activation and increased the HSF1-HSE binding activity
      (the maximal response: 2.1 fold increase at 100 micromol/L). This inducing effect
      of bicyclol on HSP27 and HSF1 was markedly blocked by quercetin. Pretreatment of
      the cells with bicyclol markedly attenuated D-GaIN-induced apoptosis and the
      release of cytochrome c and AIF from mitochondria. The induced HSP27 by bicyclol
      suppressed the activity of caspase-3 and the phosphorylation of JNK caused by D
      GaIN in HepG2 cells. All the above effect of bicyclol against D-GaIN-induced
      hepatocytes apoptosis were significantly reversed by quercetin. CONCLUSION: HSP27
      is involved in the anti-hepatocytes apoptosis of bicyclol, and this effect of
      bicyclol-induced HSP27 is mainly through inhibition of mitochondria and JNK
      apoptotic pathways.

PMID- 20139906
TI  - Microarray analysis reveals the inhibition of nuclear factor-kappa B signaling by
      aristolochic acid in normal human kidney (HK-2) cells.
AB  - AIM: To study the molecular mechanism underlying the effect of aristolochic acid
      (AA), a major active component of plants from the Aristolochiaceae family using
      microarray analysis. METHODS: Human kidney (HK-2) cells were treated with AA (0,
      10, 30, and 90 micromol/L) for 24 h, and the cell viability was measured by a 3
      (4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Complementary
      DNA microarrays were used to investigate the gene expression pattern of HK-2
      cells exposed to AA in triplicate. A quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR) assay was used to verify the microarray data
      for selected nuclear factor kappa B (NF-kappaB)-regulated genes. Furthermore, the
      subcellular localization of NF-kappaB p65 was visualized by immunofluorescence
      confocal microscopy in HK-2 cells. The NF-kappaB activity was examined by a
      luciferase reporter assay in HK-2/NF-kappaB transgenic cells. RESULTS: AA
      exhibited a dose-dependent cytotoxic effect in HK-2 cells and induced alterations
      in the gene expression profiles related to the DNA damage response, DNA repair,
      macromolecule metabolic process, carbohydrate metabolic process, DNA metabolic
      process, apoptosis, cell cycle, and transcription. In addition, 9 biological
      pathways associated with immunomodulatory functions were down-regulated in AA
      treated HK-2 cells. A network analysis revealed that NF-kappaB played a central
      role in the network topology. Among NF-kappaB-regulated genes, 8 differentially
      expressed genes were verified by qRT-PCR. The inhibition of NF-kappaB activity by
      AA was further confirmed by immunofluorescence confocal microscopy and by NF
      kappaB luciferase reporter assay. CONCLUSION: Our data revealed that AA could
      suppress NF-kappaB activity in normal human cells, perhaps partially accounting
      for the reported anti-inflammatory effects of some plants from the genus
      Aristolochia.

PMID- 20139907
TI  - Effect of lactoferrin- and transferrin-conjugated polymersomes in brain
      targeting: in vitro and in vivo evaluations.
AB  - AIM: To evaluate the effect of lactoferrin (Lf) and transferrin (Tf) in brain
      targeting. METHODS: Polymersomes (PSs), employed as vectors, were conjugated with
      Lf or Tf and were characterized by morphology, particle size, zeta potential, and
      surface densities of the Lf or Tf molecules. In vitro uptake of Lf-PS and Tf-PS
      by bEnd.3 cells was investigated using coumarin-6 as a fluorescent probe. In vivo
      tissue distribution and pharmacokinetics of (125)I-Lf-PS and (125)I-Tf-PS were
      also examined. RESULTS: The mean particle size of PS, Lf-PS, and Tf-PS was around
      150 nm and the zeta potential of the PSs was about -20 mV. Less than 0.12% of the
      coumarin was released from coumarin-6-loaded PS in 84 h indicating that coumarin
      6 was an accurate probe for the PSs' behavior in vitro. It was shown that the
      uptake of Lf-PS and Tf-PS by bEnd.3 cells was time-, temperature-, and
      concentration-dependent. Both Lf and Tf could increase the cell uptake of PSs at
      37 degrees C, but the uptake of Tf-PS was significantly greater than that of Lf
      PS. In vivo tissue distribution and pharmacokinetics in mice revealed higher
      brain uptake and distribution of Tf-PS than Lf-PS, which was in accordance with
      in vitro uptake results. The drug targeting index (DTI) of Tf-PS with regard to
      Lf-PS was 1.51. CONCLUSION: Using a PS as the delivery vector and bEnd.3 cells as
      the model of the blood-brain barrier (BBB), Tf was more effective than Lf in
      brain targeting.

PMID- 20139908
TI  - Structural studies of B-type Aurora kinase inhibitors using computational
      methods.
AB  - AIM: To characterize the structural features of quinazoline-based Aurora B
      inhibitors that influence its inhibitor activity. METHODS: Two geometrical
      methods, Method 1 and Method 2, were used to develop the 3D-QSAR models. The most
      active ligand was used as the template for the alignment of all the ligands in
      Method 1, and a conformer of the cocrystal ligand was used as the template for
      the alignment of all the ligands in Method 2. RESULTS: The models suggest that
      highly active ligands can be designed by varying the R1 substituent at position 7
      of the quinazoline ring with positively charged, bulky, hydrophobic groups, while
      bulky and hydrophobic groups around the thiazole ring are desirable for higher
      activity. CONCLUSION: This study emphasizes that the bioactive conformer is
      rather different from the minima. The steric, electrostatic, and hydrophobic
      field effects contribute to its inhibitory activity.

PMID- 20139909
TI  - Cytotoxicity and reversal of multidrug resistance by tryptanthrin-derived
      indoloquinazolines.
AB  - AIM: To evaluate the effects and elucidate the mechanisms of a series of
      indoloquinazolines as novel anticancer agents. METHODS: Condensation of the
      substituted isatoic anhydride with the substituted isatin was performed to
      prepare compounds 1-4, followed by adding malononitrile to prepare compounds 5-7.
      Cytotoxicity was measured by MTT assays. Apoptosis induction was evaluated using
      DNA fragmentation, cell cycle assay, caspase 3/7 activity and Western blot.
      RESULTS: Compounds 3, 4, and 5 display cytotoxicity against MCF-7, HeLa, SKOV3,
      and A498 cancer cells. DNA ladders appear in cells treated with compounds 3, 4,
      and 5. Within those, compound 4 exhibits the greatest activity in regards to sub
      G(1) accumulations in the cell cycle and the activation of caspase-3/7.
      Furthermore, Fas and Fas ligand levels are elevated by compound 4, implying that
      the apoptosis is in part mediated through the signals. On the other hand,
      compounds 1 and 7 display chemosensitizing activity since cytotoxicity of
      doxorubicine and etoposide is enhanced in combination with compound 1 and 7,
      respectively, in MCF-7/adr (doxorubicin-resistant) and MCF-7/vp (etoposide
      resistant). CONCLUSION: The cytotoxicity of indoloquinazolines is structure
      dependent rather than cell type-dependent due to the similar degree of
      cytotoxicity induced by the individual compounds in all four cell lines. Further
      modification of the tryptanthrin skeleton is important to develop novel
      anticancer agents bearing either cytotoxicity against MCF-7 cells or drug
      resistance reversal in MCF-7/adr and MCF-7/vp.

PMID- 20139910
TI  - Amplification of 8q21 in breast cancer is independent of MYC and associated with
      poor patient outcome.
AB  - Copy number gains involving the long arm of chromosome 8, including high-level
      amplifications at 8q21 and 8q24, have been frequently reported in breast cancer.
      Although the role of the MYC gene as the driver of the 8q24 amplicon is well
      established, the significance of the 8q21 amplicon is less clear. The breast
      cancer cell line SK-BR-3 contains three separate 8q21 amplicons, the distal two
      of which correspond to putative target genes TPD52 and WWP1. To understand the
      effect of proximal 8q21 amplification on breast cancer phenotype and patient
      prognosis, we analyzed 8q21 copy number changes using fluorescence in situ
      hybridization (FISH) in a tissue microarray containing more than 2000 breast
      cancers. Amplification at 8q21 was found in 3% of tumors, and was associated with
      medullary type (P<0.03), high tumor grade (P<0.0001), high Ki67 labeling index
      (P<0.05), amplification of MYC (P<0.0001), HER2, MDM2, and CCND1 (P<0.05 each),
      as well as the total number of gene amplifications (P<0.0001). 8q21 copy number
      gains were significantly related to unfavorable patient outcome in univariate
      analysis. However, multivariate Cox regression analysis did not reveal an
      independent prognostic value of 8q21 amplification. The position of our FISH
      probe and data of a previously performed high-resolution CGH study in the breast
      cancer cell line SK-BR-3 involve TCEB1 and TMEM70 as new possible candidate
      oncogenes at 8q21 in breast cancer.

PMID- 20139911
TI  - Eyelid necrosis after local anaesthesia for lacrimal sac surgery.

PMID- 20139912
TI  - Surgical outcome of single-staged three horizontal muscles squint surgery for
      extra-large angle exotropia.
AB  - PURPOSE: To report the surgical outcomes of 24 patients undergoing single-staged
      three horizontal muscles squint surgery for extra-large angle exotropia. PATIENTS
      AND METHODS: Prospective case series of 24 consecutive patients with primary
      exotropia>60 prism diopters (PD) at distant and underwent single-staged three
      horizontal muscles squint surgery from 2003 to 2006. Surgery consisted of
      bilateral lateral rectus recession of 9.0 mm for 50 PD exotropic correction. For
      every 5 PD remaining angle exceeding 50 PD, we additionally performed 1.0 mm of
      unilateral medial rectus resection. The mean follow-up period was 15.8 months
      (range 6.0-38.0 months; SD 9.5 months). RESULTS: The mean age at surgery was 31.2
      years old (range 7-78 years old, SD 18.2 years old). The mean distant
      preoperative deviation was 71.3 PD (range 60-85 PD, SD 7.7 PD). No limitation of
      eye movement or diplopia was found. The success rate was higher in the
      intermittent group (88.2%) than the constant group (42.9%) (P=0.02) and in cases
      with preoperative deviation of <80 PD (84.2%) compared with those with
      deviation>or=80 PD (40.0%) (P=0.042). CONCLUSION: Measurement of preoperative
      deviation and the surgery for extra-large angle exotropia made management of this
      condition difficult. Single-staged three horizontal muscles squint surgery can be
      one of the options. Further researches on management of exotropia of >80 PD are
      warranted.

PMID- 20139913
TI  - A preliminary trial to determine whether prevention of dark adaptation affects
      the course of early diabetic retinopathy.
AB  - This study was designed to determine whether a new form of treatment of diabetic
      retinopathy (DR) was acceptable to patients and whether reduction in the maximal
      activity of rods in diabetes could affect the progress of DR. METHODS: In 12
      patients, trans-lid retinal illumination of one eye was employed during sleep to
      prevent the depolarisation of rods and thus reduce their metabolic activity.
      TECHNIQUES: A headband was used to place a source of chemical light over one eye,
      with its fellow as a control. MEASUREMENTS: Colour contrast thresholds were
      measured before and after a period of treatment in treated eyes, and the changes
      were compared to those in untreated fellow eyes, and areas of 'dark retinal
      anomalies' (microaneurysms, dot haemorrhages) were measured at the same time
      points. RESULTS: Patients found this intervention to be acceptable, and no
      adverse effects were noted. In the majority of cases, and for each outcome
      measure, the treated eyes improved relative to their fellows. The intervention
      significantly reduced the tritan thresholds in treated eyes relative to their
      fellows (P=0.03), and the area of dark retinal anomalies decreased in treated
      eyes and increased in untreated eyes, with a similar probability. CONCLUSIONS:
      The study showed that this intervention is safe. Although the study was not
      powered to study efficacy, the results are promising and consistent with other
      reports that indicate the retina in DR is suffering from hypoxia; however,
      further trials should be undertaken.

PMID- 20139914
TI  - Targeted mydriasis strategies for diabetic retinopathy screening clinics.
AB  - PURPOSE: To examine factors necessitating pupil dilation to achieve gradable
      diabetic screening photographs using a digital non-mydriatic camera and to
      establish techniques to predict the need for dilation and to validate them.
      METHODS: Prospective clinic-based cross-sectional study with follow-up validation
      study. The participants' involved consecutive patients attending the diabetic
      retinopathy screening clinic at a University Hospital. Best corrected visual
      acuity, age, sex, pupil size, mean spherical equivalent, cataract grade and the
      requirement for dilation to achieve gradable photographs in 90 patients were
      recorded. Data analysis using principal component analysis and multivariate
      analysis of variance derived a set of equations to predict the requirement for
      dilation. The predictive powers of these equations were validated in an
      independent group of 51 patients. RESULTS: Smaller pupil size, denser nuclear
      colour, older age, poorer best-corrected visual acuity, cortical lens opacity and
      posterior subcapsular lens opacity were associated with the need for dilation
      (P<0.001 in all). Single variables used in isolation had a poorer predictive
      value than combining variables. Dilating patients with either a pupil size>3.75
      mm or age>59 years correctly allocates 83 and 78% of patients, respectively to
      dilation or not. Combining pupil size with age produces a decision table that
      improves the predictive value to 84%. In the validation study this table had a
      predictive value of 80%. CONCLUSION: We have produced and validated criteria
      based on a range of clinical variables for application in a clinical setting that
      allows for the development of targeted mydriasis.

PMID- 20139915
TI  - Is there an effect of perioperative blood pressure on intraoperative
      complications during phacoemulsification surgery under local anaesthesia?
AB  - PURPOSE: The practice of deferring phacoemulsification procedure on recording
      raised blood pressure (BP) in the immediate perioperative period is based on the
      perception of increased intraoperative risk. The significance of perioperative BP
      recordings on the surgical complications during phacoemulsification procedure was
      evaluated. SETTING: Hairmyres Hospitals, Lanarkshire Acute Hospitals NHS Trust.
      PATIENTS AND METHODS: Patients were classified as hypertensive on the basis of
      the British Hypertension Society Guidelines. BP recordings during preoperative
      assessment, admission, and 1-hour postoperatively were recorded in 734
      hypertensives and 740 normotensives undergoing phacoemulsification procedure. In
      addition, BP recordings in the holding area before giving local anaesthesia were
      noted in the 734 hypertensives. Patient's peri- and intraoperative complications
      during the procedure were noted. RESULTS: The mean age was 72+/-10.5 years and
      74+/-11.6 years among the hypertensives and normotensives. There was a
      significant increase in the number of hypertensives who developed isolated
      systolic hypertension in the holding area (95% confidence interval=2.82, P<0.001)
      where the mean BP was 171.38/78.31 mm Hg (+/-30.55/16.29). A total of 21
      hypertensives and 18 normotensives developed intraoperative complications during
      the phacoemulsification procedure. There was no significant difference (P=0.41)
      in the intraoperative complications between the hypertensives and normotensives.
      CONCLUSION: Perioperative increase in BP noted in the holding area among
      hypertensives did not increase the risk of surgical complications during
      phacoemulsification procedure when compared with normotensives. We recommend that
      BP should not be routinely measured in the holding area before
      phacoemulsification surgery under local anaesthesia.

PMID- 20139916
TI  - Surgical management of the late complications of proliferative diabetic
      retinopathy.
AB  - The late complications of proliferative diabetic retinopathy (PDR) comprise
      vitreous haemorrhage, tractional retinal detachment, combined tractional
      rhegmatogenous retinal detachment, and severe fibrovascular proliferation
      (including macular distortion or dragging, tractional macular oedema, and media
      opacity due to fibrovascular tissue). This article will review the indications,
      techniques, and outcomes of vitrectomy surgery to treat these conditions. A
      careful assessment of the surgical anatomy, with particular attention to the
      configuration of vitreoretinal attachments, is important when determining the
      precise surgical procedure required. The surgical outcome after diabetic
      vitrectomy has steadily improved with advances in vitreoretinal surgical
      instrumentation and technique. Significant post-operative complications may,
      however, occur including cataract formation, recurrent vitreous cavity
      haemorrhage (early or delayed), rhegmatogenous retinal detachment, and
      neovascular glaucoma. Most patients will regain or retain useful vision after
      diabetic vitrectomy, although the visual outcome does remain unpredictable. The
      development of adjunctive pharmacotherapy should enable further improvements in
      visual outcome in the future.

PMID- 20139917
TI  - Prediction of the clinical phenotype of Fabry disease based on protein sequential
      and structural information.
AB  - Fabry disease is a genetic disorder caused by a deficiency of alpha
      galactosidase, exhibiting a wide clinical spectrum, from the early-onset severe
      'classic' form to the late-onset mild 'variant' one. Recent screening of newborns
      revealed that the incidence of Fabry disease is unexpectedly high, and that the
      genotypes of patients with this disease are quite heterogeneous and many novel
      mutations have been identified in them. This suggests that a lot of Fabry
      patients will be found in an early clinical stage when the prognosis is obscure
      and a proper therapeutic schedule for them cannot be determined. Thus, it is
      significant to predict the clinical phenotype of this disease resulting from a
      novel mutation. Herein, we proposed a phenotype prediction model based on
      sequential and structural information. As far as we know, this is the first
      report of phenotype prediction for Fabry disease. First, we investigated the
      sequential and structural changes in the alpha-galactosidase molecule responsible
      for Fabry disease. The results showed that there are quite large differences in
      several properties between the classic and variant groups. We then developed a
      phenotype prediction model involving the decision tree technique. The accuracy of
      this prediction model is high (86%), and Matthew's correlation coefficient is
      also high (0.49). The phenotype predictor proposed in this paper may be useful
      for determining a proper therapeutic schedule for this disease.

PMID- 20139918
TI  - Modernization, less physical activity, more obesity and hypertension.

PMID- 20139920
TI  - Effect of moxonidine and amlodipine on serum YKL-40, plasma lipids and insulin
      sensitivity in insulin-resistant hypertensive patients-a randomized, crossover
      trial.
AB  - Moxonidine is a selective imidazoline receptor agonist with comparable blood
      pressure-lowering efficacy to first-line antihypertensives and favorable
      metabolic effects. YKL-40 (chitinase-3-1-protein) has been proposed as a new
      marker of inflammation, atherosclerosis and endothelial dysfunction in
      neoplastic, cardiovascular and metabolic diseases but has not yet been studied in
      the context of essential hypertension. Fifteen patients (10 M, 5 F; age 48+/-14
      years) with arterial hypertension and insulin resistance (HOMA-IR index >2.77) on
      at least two antihypertensive drugs were randomized to receive either moxonidine
      (0.4 mg) or amlodipine (10 mg) for two 8-week periods with a 7-day wash-out.
      Serum insulin, glucose, C-reactive protein (CRP), lipids, uric acid, YKL-40 and
      blood pressure were measured and insulin sensitivity was calculated (HOMA) at the
      beginning and end of each study phase. Mean BP decreased significantly with both
      moxonidine and amlodipine (-9.8+/-7.6 and -10.4+/-7.3 mm Hg, respectively). Serum
      high-density lipoprotein cholesterol increased with both therapies, but only
      moxonidine-affected serum triglycerides. No significant changes in serum uric
      acid, CRP, YKL-40 (2.3 and 3.3 ng ml(-1), respectively) or HOMA index (0.70+/-2.4
      and 0.76+/-2.8) were observed. There was a strong negative correlation between
      serum uric acid and YKL-40 concentration at baseline (r=-0.77, P=0.01). Serum YKL
      40 did not correlate with blood pressure, biochemical parameters or HOMA index.
      Moxonidine is an effective adjunctive antihypertensive agent for use in patients
      with hypertension and insulin resistance that induces beneficial effects on serum
      lipid profile but does not reduce insulin resistance, inflammation or serum YKL
      40 concentration.

PMID- 20139919
TI  - Increased leukocyte rho kinase (ROCK) activity and endothelial dysfunction in
      cigarette smokers.
AB  - Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis
      of atherosclerosis. Although smoking is associated with endothelial dysfunction
      and ROCK inhibitors improve endothelial function in smokers, it is not known
      whether ROCK activity is increased in smokers and whether this correlates with
      endothelial dysfunction. The purpose of this study was to evaluate the
      relationship between ROCK activity and endothelial function in smokers. We
      evaluated flow-mediated vasodilatation (FMD) using ultrasonography and ROCK
      activity in peripheral leukocytes using western blot analysis in 14 male smokers
      (28.1+/-3.9 years) and 15 healthy male non-smokers (28.3+/-3.6 years). ROCK
      activity was defined as the ratio of phospho-myosin-binding subunit (MBS) on
      myosin light-chain phosphatase to total MBS. FMD was significantly less in
      smokers than in non-smokers (4.7+/-3.1 vs. 9.0+/-3.8%, P=0.005). Nitroglycerine
      induced vasodilation was similar in the two groups. ROCK activity was greater in
      smokers than in non-smokers (0.78+/-0.27 vs. 0.54+/-018, P=0.012). The expression
      of total MBS, ROCK1 and ROCK2 were similar in the two groups. ROCK activity
      correlated with systolic blood pressure (r=0.42, P=0.039). Multiple regression
      analysis revealed that smoking is an independent predictor of ROCK activity.
      There was a significant correlation between FMD and ROCK activity (r=-0.42,
      P=0.035). No other variable was correlated with FMD. These findings suggest that
      ROCK activity is enhanced by smoking and is a predictor of endothelial function.

PMID- 20139921
TI  - Significance of the second peak of systolic blood pressure for identifying both
      high and low cardiovascular risk states.
AB  - This study was conducted to clarify whether the second peak of the systolic blood
      pressure (SBP2) has significant information about cardiovascular (CV) risk state,
      independent of the brachial BP. SBP2 was measured by radial pressure wave
      analysis in 7847 Japanese subjects (50+/-10 years old), and the Framingham risk
      score (FRS) and general cardiovascular disease risk score were calculated
      (FRSgen). The results of multivariate analysis revealed that the SBP2 showed a
      significant correlation with the FRS (beta=0.04, t-value=3.92, P<0.01) and FRSgen
      (beta=0.05, t-value=6.55, P<0.01), independent of the brachial SBP. The non
      standardization coefficient of SBP2 was smaller than that of brachial SBP. The
      logistic regression analysis showed that SBP2 (2 mm Hg per increase) had a
      significant odds ratio to identify not only subjects with a high risk for
      coronary heart disease (CHD) and general CV disease (CVDgen), but also subjects
      with a low risk for CHD and CVDgen, independent of the brachial SBP. However,
      when the analysis was limited to subjects of >or=49 years of age, SBP2 could not
      identify either high or low CV risk subjects. Thus, in middle-aged Japanese
      subjects, SBP2 may provide little, yet significant, information reflecting both
      high and low CV risk states, independent of the brachial BP. SBP2 seems to be
      more applicable for CV risk stratification in younger subjects than in older
      subjects.

PMID- 20139922
TI  - CAVI vs. pressure and stiffness gradients in the arterial tree.

PMID- 20139923
TI  - Incremental predictive value of carotid intima-media thickness to arterial
      stiffness for impaired coronary flow reserve in untreated hypertensives.
AB  - Coronary microcirculation is disturbed in patients with arterial hypertension.
      Carotid intima-media thickness (IMT) and arterial stiffness are markers of
      subclinical atherosclerosis with prognostic significance. We investigated whether
      the combination of increased carotid IMT and arterial stiffness has a greater
      predictive value for the presence of impaired coronary flow reserve (CFR) than
      each index alone in never-treated hypertensives. We studied 110 untreated
      patients (age: 54.5+/-12 years) with newly diagnosed arterial hypertension. We
      measured (1) carotid-to-femoral artery pulse wave velocity (PWV), (2) carotid IMT
      and (3) CFR by means of color-guided Doppler echocardiography after adenosine
      infusion. Among other confounders, arterial stiffness and IMT were independent
      determinants of CFR (coefficient B=-0.146 and B=-0.006, P<0.05). Arterial
      stiffness and IMT had an incremental value for the determination of CFR when
      added to a model including other confounders (chi(2) change=4.423, P for
      change=0.038 after addition of IMT; and chi(2) change=5.369, P for change=0.020
      after addition of PWV). Receiver operating curve analysis showed that PWV>10.2 m
      s(-1) and IMT>1 mm were the optimal cutoff values to predict a CFR<2.5. Patients
      with IMT>1 mm, PWV>10.2 m s(-1) or their combination had an odds ratio of 3.5,
      5.0 and 11.2, P<0.05, for a CFR<2.5, respectively. The combination of increased
      carotid IMT and arterial stiffness has a greater predictive value for impaired
      CFR than each index alone in never-treated hypertensives.

PMID- 20139924
TI  - Adenoviral targeting of gene expression to tumors.
AB  - Using biochemical, imaging and histological methods, we employed transcriptional
      targeting to increase the specificity of tumor gene expression in vivo for
      intravenously administered recombinant adenovirus vectors. Surprisingly, the
      relative specificity of tumor expression in comparison with other tissues was
      increased for a constitutively expressing recombinant adenovirus, AdCMVLuc, by
      simply reducing the viral dose. Even at lower doses, however, the high frequency
      of viral infection and transgene expression in the liver using constitutive
      promoters still represents a substantial problem. To further augment tumor
      specificity, we constructed a series of adenoviruses expressing luciferase from
      several other promoters and tested their ability to selectively transcribe genes
      in tumor cells, both in vitro and in vivo. Constitutively active viral promoters
      (RSV, SRalpha) varied widely in their tumor selectivity, but hypoxia-responsive
      promoters (carbonic anhydrase 9, PAI-1, SOD2 and several chimeric constructs)
      showed the most tumor-selective expression. Our results show that tumor targeting
      to HT1080 fibrosarcomas was readily achieved using transcriptional targeting
      mechanisms. We attribute the relatively high level of gene transfer and
      expression in HT1080 tumors in vivo to increased viral access to the tumor,
      presumably due to discontinuities in tumor vasculature and augmented expression
      from stress-responsive promoters in the hypoxic and inflammatory tumor
      microenvironment.

PMID- 20139925
TI  - Impossible fixes.

PMID- 20139926
TI  - PhRMA wants you!

PMID- 20139927
TI  - PML problems loom for Rituxan.

PMID- 20139928
TI  - Pfizer stakes a claim in plant cell-made biopharmaceuticals.

PMID- 20139929
TI  - Amylin's $1 billion heavyweight deal.

PMID- 20139930
TI  - EC convenes crisis talks on European biotech sector.

PMID- 20139932
TI  - Report blames GM crops for herbicide spike, downplays pesticide reductions.

PMID- 20139938
TI  - FDA balks on MedImmune's cell-grown flu vaccine.

PMID- 20139940
TI  - Coming to terms.

PMID- 20139941
TI  - The HER2 testing conundrum.

PMID- 20139942
TI  - Fab-arm exchange.

PMID- 20139944
TI  - An economic and technical evaluation of microalgal biofuels.

PMID- 20139946
TI  - Never again.

PMID- 20139945
TI  - Ontology engineering.

PMID- 20139947
TI  - Going to ridiculous lengths--European coexistence regulations for GM crops.

PMID- 20139948
TI  - Changing the rules of the game: addressing the conflict between free access to
      scientific discovery and intellectual property rights.

PMID- 20139950
TI  - ChIPs and regulatory bits.

PMID- 20139951
TI  - From genomics to crop breeding.

PMID- 20139952
TI  - Spilling the beans on legume biology.

PMID- 20139953
TI  - Systematic tracking of cell fate changes.

PMID- 20139961
TI  - Fourth quarter lag in biotech hiring.

PMID- 20139963
TI  - Organic-walled microfossils in 3.2-billion-year-old shallow-marine siliciclastic
      deposits.
AB  - Although the notion of an early origin and diversification of life on Earth
      during the Archaean eon has received increasing support in geochemical,
      sedimentological and palaeontological evidence, ambiguities and controversies
      persist regarding the biogenicity and syngeneity of the record older than Late
      Archaean. Non-biological processes are known to produce morphologies similar to
      some microfossils, and hydrothermal fluids have the potential to produce abiotic
      organic compounds with depleted carbon isotope values, making it difficult to
      establish unambiguous traces of life. Here we report the discovery of a
      population of large (up to about 300 mum in diameter) carbonaceous spheroidal
      microstructures in Mesoarchaean shales and siltstones of the Moodies Group, South
      Africa, the Earth's oldest siliciclastic alluvial to tidal-estuarine deposits.
      These microstructures are interpreted as organic-walled microfossils on the basis
      of petrographic and geochemical evidence for their endogenicity and syngeneity,
      their carbonaceous composition, cellular morphology and ultrastructure,
      occurrence in populations, taphonomic features of soft wall deformation, and the
      geological context plausible for life, as well as a lack of abiotic explanation
      falsifying a biological origin. These are the oldest and largest Archaean organic
      walled spheroidal microfossils reported so far. Our observations suggest that
      relatively large microorganisms cohabited with earlier reported benthic microbial
      mats in the photic zone of marginal marine siliciclastic environments 3.2 billion
      years ago.

PMID- 20139964
TI  - Enzyme-inhibitor-like tuning of Ca(2+) channel connectivity with calmodulin.
AB  - Ca(2+) channels and calmodulin (CaM) are two prominent signalling hubs that
      synergistically affect functions as diverse as cardiac excitability, synaptic
      plasticity and gene transcription. It is therefore fitting that these hubs are in
      some sense coordinated, as the opening of Ca(V)1-2 Ca(2+) channels are regulated
      by a single CaM constitutively complexed with channels. The Ca(2+)-free form of
      CaM (apoCaM) is already pre-associated with the isoleucine-glutamine (IQ) domain
      on the channel carboxy terminus, and subsequent Ca(2+) binding to this 'resident'
      CaM drives conformational changes that then trigger regulation of channel
      opening. Another potential avenue for channel-CaM coordination could arise from
      the absence of Ca(2+) regulation in channels lacking a pre-associated CaM.
      Natural fluctuations in CaM concentrations might then influence the fraction of
      regulable channels and, thereby, the overall strength of Ca(2+) feedback.
      However, the prevailing view has been that the ultrastrong affinity of channels
      for apoCaM ensures their saturation with CaM, yielding a significant form of
      concentration independence between Ca(2+) channels and CaM. Here we show that
      significant exceptions to this autonomy exist, by combining electrophysiology (to
      characterize channel regulation) with optical fluorescence resonance energy
      transfer (FRET) sensor determination of free-apoCaM concentration in live cells.
      This approach translates quantitative CaM biochemistry from the traditional test
      tube context into the realm of functioning holochannels within intact cells. From
      this perspective, we find that long splice forms of Ca(V)1.3 and Ca(V)1.4
      channels include a distal carboxy tail that resembles an enzyme competitive
      inhibitor that retunes channel affinity for apoCaM such that natural CaM
      variations affect the strength of Ca(2+) feedback modulation. Given the ubiquity
      of these channels, the connection between ambient CaM levels and Ca(2+) entry
      through channels is broadly significant for Ca(2+) homeostasis. Strategies such
      as ours promise key advances for the in situ analysis of signalling molecules
      resistant to in vitro reconstitution, such as Ca(2+) channels.

PMID- 20139965
TI  - Tbx3 improves the germ-line competency of induced pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells can be obtained by the introduction of
      defined factors into somatic cells. The combination of Oct4 (also known as
      Pou5f1), Sox2 and Klf4 (which we term OSK) constitutes the minimal requirement
      for generating iPS cells from mouse embryonic fibroblasts. These cells are
      thought to resemble embryonic stem cells (ESCs) on the basis of global gene
      expression analyses; however, few studies have tested the ability and efficiency
      of iPS cells to contribute to chimaerism, colonization of germ tissues, and most
      importantly, germ-line transmission and live birth from iPS cells produced by
      tetraploid complementation. Using genomic analyses of ESC genes that have roles
      in pluripotency and fusion-mediated somatic cell reprogramming, here we show that
      the transcription factor Tbx3 significantly improves the quality of iPS cells.
      iPS cells generated with OSK and Tbx3 (OSKT) are superior in both germ-cell
      contribution to the gonads and germ-line transmission frequency. However, global
      gene expression profiling could not distinguish between OSK and OSKT iPS cells.
      Genome-wide chromatin immunoprecipitation sequencing analysis of Tbx3-binding
      sites in ESCs suggests that Tbx3 regulates pluripotency-associated and
      reprogramming factors, in addition to sharing many common downstream regulatory
      targets with Oct4, Sox2, Nanog and Smad1. This study underscores the intrinsic
      qualitative differences between iPS cells generated by different methods, and
      highlights the need to rigorously characterize iPS cells beyond in vitro studies.

PMID- 20139966
TI  - Transition from a strong-yet-brittle to a stronger-and-ductile state by size
      reduction of metallic glasses.
AB  - Amorphous metallic alloys, or metallic glasses, are lucrative engineering
      materials owing to their superior mechanical properties such as high strength and
      large elastic strain. However, their main drawback is their propensity for highly
      catastrophic failure through rapid shear banding, significantly undercutting
      their structural applications. Here, we show that when reduced to 100 nm, Zr
      based metallic glass nanopillars attain ceramic-like strengths (2.25 GPa) and
      metal-like ductility (25%) simultaneously. We report separate and distinct
      critical sizes for maximum strength and for the brittle-to-ductile transition,
      thereby demonstrating that strength and ability to carry plasticity are decoupled
      at the nanoscale. A phenomenological model for size dependence and brittle-to
      homogeneous deformation is provided.

PMID- 20139967
TI  - A nonviral minicircle vector for deriving human iPS cells.
AB  - Owing to the risk of insertional mutagenesis, viral transduction has been
      increasingly replaced by nonviral methods to generate induced pluripotent stem
      cells (iPSCs). We report the use of 'minicircle' DNA, a vector type that is free
      of bacterial DNA and capable of high expression in cells, for this purpose. Here
      we use a single minicircle vector to generate transgene-free iPSCs from adult
      human adipose stem cells.

PMID- 20139968
TI  - Silencing neurotransmission with membrane-tethered toxins.
AB  - At synaptic terminals, high voltage-activated Ca(v)2.1 and Ca(v)2.2 calcium
      channels have an essential and joint role in coupling the presynaptic action
      potential to neurotransmitter release. Here we show that membrane-tethered toxins
      allowed cell-autonomous blockade of each channel individually or simultaneously
      in mouse neurons in vivo. We report optimized constitutive, inducible and Cre
      recombinase-dependent lentiviral vectors encoding fluorescent recombinant toxins,
      and we also validated the toxin-based strategy in a transgenic mouse model.
      Toxins delivered by lentiviral vectors selectively inhibited the dopaminergic
      nigrostriatal pathway, and transgenic mice with targeted expression in
      nociceptive peripheral neurons displayed long-lasting suppression of chronic
      pain. Optimized tethered toxins are tools for cell-specific and temporal
      manipulation of ion channel-mediated activities in vivo, including blockade of
      neurotransmitter release.

PMID- 20139969
TI  - Computational prediction of neural progenitor cell fates.
AB  - Understanding how stem and progenitor cells choose between alternative cell fates
      is a major challenge in developmental biology. Efforts to tackle this problem
      have been hampered by the scarcity of markers that can be used to predict cell
      division outcomes. Here we present a computational method, based on algorithmic
      information theory, to analyze dynamic features of living cells over time. Using
      this method, we asked whether rat retinal progenitor cells (RPCs) display
      characteristic phenotypes before undergoing mitosis that could foretell their
      fate. We predicted whether RPCs will undergo a self-renewing or terminal division
      with 99% accuracy, or whether they will produce two photoreceptors or another
      combination of offspring with 87% accuracy. Our implementation can segment, track
      and generate predictions for 40 cells simultaneously on a standard computer at 5
      min per frame. This method could be used to isolate cell populations with
      specific developmental potential, enabling previously impossible investigations.

PMID- 20139970
TI  - MAZe: a tool for mosaic analysis of gene function in zebrafish.
AB  - To trace cell lineages in a developing vertebrate and to observe, in vivo, how
      behaviors of individual cells are affected by the genes they express, we created
      a zebrafish line containing a transgene called mosaic analysis in zebrafish
      (MAZe), built around a self-excising hsp70:Cre cassette. Heat shock triggers Cre
      recombinase-mediated recombination in a random subset of cells, bringing the
      transcriptional activator Gal4:VP16 under control of the EF1alpha promoter. Gal4
      VP16 then activates expression of a fluorescent protein from an upstream
      activating sequence (UAS) promoter. Marked clones of cells expressing any desired
      gene product can be generated by crossing MAZe fish with other lines containing
      UAS-driven transgenes. The number of clones induced, and their time of origin,
      could be varied by adjusting heat-shock timing and duration. As an alternative to
      heat shock, we introduced Cre under a tissue-specific promoter in MAZe fish to
      generate clones in a designated tissue.

PMID- 20139971
TI  - Histone H3 Thr 45 phosphorylation is a replication-associated post-translational
      modification in S. cerevisiae.
AB  - Post-translational histone modifications are crucial for the regulation of
      numerous DNA-templated processes, and are thought to mediate both alteration of
      chromatin dynamics and recruitment of effector proteins to specific regions of
      the genome. In particular, histone Ser/Thr phosphorylation regulates multiple
      nuclear functions in the budding yeast Saccharomyces cerevisiae, including
      transcription, DNA damage repair, mitosis, apoptosis and sporulation. Although
      modifications to chromatin during replication remain poorly understood, a number
      of recent studies have described acetylation of the histone H3 N-terminal alpha
      helix (alphaN helix) at Lys 56 as a modification that is important for
      maintenance of genomic integrity during DNA replication and repair. Here, we
      report phosphorylation of H3 Thr 45 (H3-T45), a histone modification also located
      within the H3 alphaN helix in S. cerevisiae. Thr 45 phosphorylation peaks during
      DNA replication, and is mediated by the S phase kinase Cdc7-Dbf4 as part of a
      multiprotein complex identified in this study. Furthermore, loss of
      phosphorylated H3-T45 causes phenotypes consistent with replicative defects, and
      prolonged replication stress results in H3-T45 phosphorylation accumulation over
      time. Notably, the phenotypes described here are independent of Lys 56
      acetylation status, and combinatorial mutations to both Thr 45 and Lys 56 of H3
      cause synthetic growth defects. Together, these data identify and characterize H3
      T45 phosphorylation as a replication-associated histone modification in budding
      yeast.

PMID- 20139972
TI  - TGF-beta type II receptor phosphorylates PTH receptor to integrate bone
      remodelling signalling.
AB  - Parathyroid hormone (PTH) regulates calcium homeostasis and bone metabolism by
      activating PTH type I receptor (PTH1R). Here we show that transforming growth
      factor (TGF)-beta type II receptor (TbetaRII) forms an endocytic complex with
      PTH1R in response to PTH and regulates signalling by PTH and TGF-beta. TbetaRII
      directly phosphorylates the PTH1R cytoplasmic domain, which modulates PTH-induced
      endocytosis of the PTH1R-TbetaRII complex. Deletion of TbetaRII in osteoblasts
      increases the cell-surface expression of PTH1R and augments PTH signalling.
      Conditional knockout of TbetaRII in osteoblasts in mice results in a high bone
      mass with increased trabecular bone and decreased cortical bone, similar to the
      bone phenotype in mice expressing a constitutively active PTH1R. Disruption of
      PTH signalling by injection of PTH(7-34) or ablation of PTH1R rescues the bone
      phenotype of TbetaRII knockout mice. These studies reveal a previously
      unrecognized function for TbetaRII and a mechanism for integration of PTH and
      local growth factor at the membrane receptor level.

PMID- 20139973
TI  - Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase
      signaling.
AB  - To assess the importance of brain cytochrome P450 (P450) activity in mu opioid
      analgesic action, we generated a mutant mouse with brain neuron-specific
      reductions in P450 activity; these mice showed highly attenuated morphine
      antinociception compared with controls. Pharmacological inhibition of brain P450
      arachidonate epoxygenases also blocked morphine antinociception in mice and rats.
      Our findings indicate that a neuronal P450 epoxygenase mediates the pain
      relieving properties of morphine.

PMID- 20139974
TI  - Bimodal control of stimulated food intake by the endocannabinoid system.
AB  - Activation of cannabinoid type-1 receptors (CB(1)) is universally recognized as a
      powerful endogenous orexigenic signal, but the detailed underlying neuronal
      mechanisms are not fully understood. Using combined genetic and pharmacological
      approaches in mice, we found that ventral striatal CB(1) receptors exerted a
      hypophagic action through inhibition of GABAergic transmission. Conversely, brain
      CB(1) receptors modulating excitatory transmission mediated the well-known
      orexigenic effects of cannabinoids.

PMID- 20139975
TI  - Diversity and wiring variability of olfactory local interneurons in the
      Drosophila antennal lobe.
AB  - Local interneurons are essential in information processing by neural circuits.
      Here we present a comprehensive genetic, anatomical and electrophysiological
      analysis of local interneurons (LNs) in the Drosophila melanogaster antennal
      lobe, the first olfactory processing center in the brain. We found LNs to be
      diverse in their neurotransmitter profiles, connectivity and physiological
      properties. Analysis of >1,500 individual LNs revealed principal morphological
      classes characterized by coarsely stereotyped glomerular innervation patterns.
      Some of these morphological classes showed distinct physiological properties.
      However, the finer-scale connectivity of an individual LN varied considerably
      across brains, and there was notable physiological variability within each
      morphological or genetic class. Finally, LN innervation required interaction with
      olfactory receptor neurons during development, and some individual variability
      also likely reflected LN-LN interactions. Our results reveal an unexpected degree
      of complexity and individual variation in an invertebrate neural circuit, a
      result that creates challenges for solving the Drosophila connectome.

PMID- 20139976
TI  - Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse
      via Rac1.
AB  - Synaptic spines are dynamic structures that regulate neuronal responsiveness and
      plasticity. We examined the role of the schizophrenia risk factor DISC1 in the
      maintenance of spine morphology and function. We found that DISC1 anchored
      Kalirin-7 (Kal-7), regulating access of Kal-7 to Rac1 and controlling the
      duration and intensity of Rac1 activation in response to NMDA receptor activation
      in both cortical cultures and rat brain in vivo. These results explain why Rac1
      and its activator (Kal-7) serve as important mediators of spine enlargement and
      why constitutive Rac1 activation decreases spine size. This mechanism likely
      underlies disturbances in glutamatergic neurotransmission that have been
      frequently reported in schizophrenia that can lead to alteration of dendritic
      spines with consequential major pathological changes in brain function.
      Furthermore, the concept of a signalosome involving disease-associated factors,
      such as DISC1 and glutamate, may well contribute to the multifactorial and
      polygenetic characteristics of schizophrenia.

PMID- 20139977
TI  - Common variants near TERC are associated with mean telomere length.
AB  - We conducted genome-wide association analyses of mean leukocyte telomere length
      in 2,917 individuals, with follow-up replication in 9,492 individuals. We
      identified an association with telomere length on 3q26 (rs12696304, combined P =
      3.72 x 10(-14)) at a locus that includes TERC, which encodes the telomerase RNA
      component. Each copy of the minor allele of rs12696304 was associated with an
      approximately 75-base-pair reduction in mean telomere length, equivalent to
      approximately 3.6 years of age-related telomere-length attrition.

PMID- 20139978
TI  - Genome-wide association study of hematological and biochemical traits in a
      Japanese population.
AB  - We report genome-wide association studies for hematological and biochemical
      traits from approximately 14,700 Japanese individuals. We identified 60
      associations for 8 hematological traits and 29 associations for 12 biochemical
      traits at genome-wide significance levels (P < 5 x 10(-8)). Of these, 46
      associations were new to this study and 43 replicated previous reports. We
      compared these associated loci with those reported in similar GWAS in European
      populations. When the minor allele frequency was >10% in the Japanese population,
      32 (94.1%) and 31 (91.2%) of the 34 hematological loci previously reported to be
      associated in a European population were replicated with P-values less than 0.05
      and 0.01, respectively, and 31 (73.8%) and 27 (64.3%) of the 42 European
      biochemical loci were replicated.

PMID- 20139979
TI  - A basic helix-loop-helix transcription factor controls cell growth and size in
      root hairs.
AB  - Postmitotic cell growth defines cell shape and size during development. However,
      the mechanisms regulating postmitotic cell growth in plants remain unknown. Here
      we report the discovery of a basic helix-loop-helix (bHLH) transcription factor
      called RSL4 (ROOT HAIR DEFECTIVE 6-LIKE 4) that is sufficient to promote
      postmitotic cell growth in Arabidopsis thaliana root-hair cells. Loss of RSL4
      function resulted in the development of very short root hairs. In contrast,
      constitutive RSL4 expression programmed constitutive growth, resulting in the
      formation of very long root hairs. Hair-cell growth signals, such as auxin and
      low phosphate availability, modulate hair cell extension by regulating RSL4
      transcript and protein levels. RSL4 is thus a regulator of growth that integrates
      endogenous developmental and exogenous environmental signals that together
      control postmitotic growth in root hairs. The control of postmitotic growth by
      transcription factors may represent a general mechanism for regulating cell size
      across diverse organisms.

PMID- 20139980
TI  - Identification of DOK genes as lung tumor suppressors.
AB  - Genome-wide analyses of human lung adenocarcinoma have identified regions of
      consistent copy-number gain or loss, but in many cases the oncogenes and tumor
      suppressors presumed to reside in these loci remain to be determined. Here we
      identify the downstream of tyrosine kinase (Dok) family members Dok1, Dok2 and
      Dok3 as lung tumor suppressors. Single, double or triple compound loss of these
      genes in mice results in lung cancer, with penetrance and latency dependent on
      the number of lost Dok alleles. Cancer development is preceded by an aberrant
      expansion and signaling profile of alveolar type II cells and bronchioalveolar
      stem cells. In human lung adenocarcinoma, we identify DOK2 as a target of copy
      number loss and mRNA downregulation and find that DOK2 suppresses lung cancer
      cell proliferation in vitro and in vivo. Given the genomic localization of DOK2,
      we propose it as an 8p21.3 haploinsufficient human lung tumor suppressor.

PMID- 20139981
TI  - alpha-Helical nascent polypeptide chains visualized within distinct regions of
      the ribosomal exit tunnel.
AB  - As translation proceeds, the nascent polypeptide chain passes through a tunnel in
      the large ribosomal subunit. Although this ribosomal exit tunnel was once thought
      only to be a passive conduit for the growing nascent chain, accumulating evidence
      suggests that it may in fact play a more active role in regulating translation
      and initial protein folding events. Here we have determined single-particle cryo
      electron microscopy reconstructions of eukaryotic 80S ribosomes containing
      nascent chains with high alpha-helical propensity located within the exit tunnel.
      The maps enable direct visualization of density for helices as well as allowing
      the sites of interaction with the tunnel wall components to be elucidated. In
      particular regions of the tunnel, the nascent chain adopts distinct conformations
      and establishes specific contacts with tunnel components, both ribosomal RNA and
      proteins, that have been previously implicated in nascent chain-ribosome
      interaction.

PMID- 20139982
TI  - Systematic identification of fragile sites via genome-wide location analysis of
      gamma-H2AX.
AB  - Phosphorylation of histone H2AX is an early response to DNA damage in eukaryotes.
      In Saccharomyces cerevisiae, DNA damage or replication-fork stalling results in
      phosphorylation of histone H2A yielding gamma-H2A (yeast gamma-H2AX) in a Mec1
      (ATR)- and Tel1 (ATM)-dependent manner. Here, we describe the genome-wide
      location analysis of gamma-H2A as a strategy to identify loci prone to engaging
      the Mec1 and Tel1 pathways. Notably, gamma-H2A enrichment overlaps with loci
      prone to replication-fork stalling and is caused by the action of Mec1 and Tel1,
      indicating that these loci are prone to breakage. Moreover, about half the sites
      enriched for gamma-H2A map to repressed protein-coding genes, and histone
      deacetylases are necessary for formation of gamma-H2A at these loci. Finally, our
      work indicates that high-resolution mapping of gamma-H2AX is a fruitful route to
      map fragile sites in eukaryotic genomes.

PMID- 20139983
TI  - Intersubunit capture of regulatory segments is a component of cooperative CaMKII
      activation.
AB  - The dodecameric holoenzyme of calcium-calmodulin-dependent protein kinase II
      (CaMKII) responds to high-frequency Ca(2+) pulses to become Ca(2+) independent. A
      simple coincidence-detector model for Ca(2+)-frequency dependency assumes
      noncooperative activation of kinase domains. We show that activation of CaMKII by
      Ca(2+)-calmodulin is cooperative, with a Hill coefficient of approximately 3.0,
      implying sequential kinase-domain activation beyond dimeric units. We present
      data for a model in which cooperative activation includes the intersubunit
      'capture' of regulatory segments. Such a capture interaction is seen in a crystal
      structure that shows extensive contacts between the regulatory segment of one
      kinase and the catalytic domain of another. These interactions are mimicked by a
      natural inhibitor of CaMKII. Our results show that a simple coincidence-detection
      model cannot be operative and point to the importance of kinetic dissection of
      the frequency-response mechanism in future experiments.

PMID- 20139984
TI  - SF2/ASF autoregulation involves multiple layers of post-transcriptional and
      translational control.
AB  - SF2/ASF is a prototypical serine- and arginine-rich protein, with important roles
      in splicing and other aspects of mRNA metabolism. Splicing factor,
      arginine/serine-rich 1 (SFRS1), the gene encoding SF2/ASF, is a potent proto
      oncogene with abnormal expression in many tumors. We found that SF2/ASF
      negatively autoregulates its expression to maintain homeostatic levels. We
      characterized six alternatively spliced SF2/ASF mRNA isoforms: the major isoform
      encodes full-length protein, whereas the others are either retained in the
      nucleus or degraded by nonsense-mediated mRNA decay. Unproductive splicing
      accounts for only part of the autoregulation, which occurs primarily at the
      translational level. The effect is specific to SF2/ASF and requires RNA
      recognition motif 2 (RRM2). The ultraconserved 3' untranslated region (UTR) is
      necessary and sufficient for downregulation. SF2/ASF overexpression shifts the
      distribution of target mRNA toward monoribosomes, and translational repression is
      partly independent of Dicer and a 5' cap. Thus, multiple post-transcriptional and
      translational mechanisms are involved in fine-tuning the expression of SF2/ASF.

PMID- 20139985
TI  - One SNARE complex is sufficient for membrane fusion.
AB  - In eukaryotes, most intracellular membrane fusion reactions are mediated by the
      interaction of SNARE proteins that are present in both fusing membranes. However,
      the minimal number of SNARE complexes needed for membrane fusion is not known.
      Here we show unambiguously that one SNARE complex is sufficient for membrane
      fusion. We performed controlled in vitro Forster resonance energy transfer (FRET)
      experiments and found that liposomes bearing only a single SNARE molecule are
      still capable of fusion with other liposomes or with purified synaptic vesicles.
      Furthermore, we demonstrated that multiple SNARE complexes do not act
      cooperatively, showing that synergy between several SNARE complexes is not needed
      for membrane fusion. Our findings shed new light on the mechanism of SNARE
      mediated membrane fusion and call for a revision of current views of fusion
      events such as the fast release of neurotransmitters.

PMID- 20139986
TI  - Chromogranin A is an autoantigen in type 1 diabetes.
AB  - Autoreactive CD4(+) T cells are involved in the pathogenesis of many autoimmune
      diseases, but the antigens that stimulate their responses have been difficult to
      identify and in most cases are not well defined. In the nonobese diabetic (NOD)
      mouse model of type 1 diabetes, we have identified the peptide WE14 from
      chromogranin A (ChgA) as the antigen for highly diabetogenic CD4(+) T cell
      clones. Peptide truncation and extension analysis shows that WE14 bound to the
      NOD mouse major histocompatibility complex class II molecule I-A(g7) in an
      atypical manner, occupying only the carboxy-terminal half of the I-A(g7) peptide
      binding groove. This finding extends the list of T cell antigens in type 1
      diabetes and supports the idea that autoreactive T cells respond to unusually
      presented self peptides.

PMID- 20139987
TI  - HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of
      reactive oxygen species.
AB  - Voltage-gated proton currents regulate generation of reactive oxygen species
      (ROS) in phagocytic cells. In B cells, stimulation of the B cell antigen receptor
      (BCR) results in the production of ROS that participate in B cell activation, but
      the involvement of proton channels is unknown. We report here that the voltage
      gated proton channel HVCN1 associated with the BCR complex and was internalized
      together with the BCR after activation. BCR-induced generation of ROS was lower
      in HVCN1-deficient B cells, which resulted in attenuated BCR signaling via
      impaired BCR-dependent oxidation of the tyrosine phosphatase SHP-1. This resulted
      in less activation of the kinases Syk and Akt, impaired mitochondrial respiration
      and glycolysis and diminished antibody responses in vivo. Our findings identify
      unanticipated functions for proton channels in B cells and demonstrate the
      importance of ROS in BCR signaling and downstream metabolism.

PMID- 20139988
TI  - Raising the NKT cell family.
AB  - Natural killer T cells (NKT cells) are CD1d-restricted, lipid antigen-reactive,
      immunoregulatory T lymphocytes that can promote cell-mediated immunity to tumors
      and infectious organisms, including bacteria and viruses, yet paradoxically they
      can also suppress the cell-mediated immunity associated with autoimmune disease
      and allograft rejection. Furthermore, in some diseases, such as atherosclerosis
      and allergy, NKT cell activity can be deleterious to the host. Although the
      precise means by which these cells carry out such contrasting functions is
      unclear, recent studies have highlighted the existence of many functionally
      distinct NKT cell subsets. Because their frequency and number vary widely between
      individuals, it is important to understand the mechanisms that regulate the
      development and maintenance of NKT cells and subsets thereof, which is the
      subject of this review.

PMID- 20139989
TI  - Agmatine-conjugated cytidine in a tRNA anticodon is essential for AUA decoding in
      archaea.
AB  - A modified base at the first (wobble) position of some tRNA anticodons is
      critical for deciphering the genetic code. In eukaryotes and eubacteria, AUA
      codons are decoded by tRNAsIle with modified bases pseudouridine (and/or inosine)
      and lysidine, respectively. The mechanism by which archaeal species translate AUA
      codons is unclear. We describe a polyamine-conjugated modified base, 2
      agmatinylcytidine (agm(2)C or agmatidine), at the wobble position of archaeal
      tRNA(Ile) that decodes AUA codons specifically. We demonstrate that archaeal
      cells use agmatine to synthesize agm(2)C of tRNA(Ile). We also identified a new
      enzyme, tRNA(Ile)-agm(2)C synthetase (TiaS), that catalyzes agm(2)C formation in
      the presence of agmatine and ATP. Although agm(2)C is chemically similar to
      lysidine, TiaS constitutes a distinct class of enzyme from tRNA(Ile)-lysidine
      synthetase (TilS), suggesting that the decoding systems evolved convergently
      across domains.

PMID- 20139990
TI  - Chemical phylogenetics of histone deacetylases.
AB  - The broad study of histone deacetylases in chemistry, biology and medicine relies
      on tool compounds to derive mechanistic insights. A phylogenetic analysis of
      class I and II histone deacetylases (HDACs) as targets of a comprehensive,
      structurally diverse panel of inhibitors revealed unexpected isoform selectivity
      even among compounds widely perceived as nonselective. The synthesis and study of
      a focused library of cinnamic hydroxamates allowed the identification of, to our
      knowledge, the first nonselective HDAC inhibitor. These data will guide a more
      informed use of HDAC inhibitors as chemical probes and therapeutic agents.

PMID- 20139991
TI  - Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone
      anabolic treatment for osteoporosis.
AB  - Osteoporosis is a disease of low bone mass most often caused by an increase in
      bone resorption that is not sufficiently compensated for by a corresponding
      increase in bone formation. As gut-derived serotonin (GDS) inhibits bone
      formation, we asked whether hampering its biosynthesis could treat osteoporosis
      through an anabolic mechanism (that is, by increasing bone formation). We
      synthesized and used LP533401, a small molecule inhibitor of tryptophan
      hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis. Oral
      administration of this small molecule once daily for up to six weeks acts
      prophylactically or therapeutically, in a dose-dependent manner, to treat
      osteoporosis in ovariectomized rodents because of an isolated increase in bone
      formation. These results provide a proof of principle that inhibiting GDS
      biosynthesis could become a new anabolic treatment for osteoporosis.

PMID- 20139993
TI  - The challenge of dementia therapy.

PMID- 20139992
TI  - Development of replication-defective lymphocytic choriomeningitis virus vectors
      for the induction of potent CD8+ T cell immunity.
AB  - Lymphocytic choriomeningitis virus (LCMV) exhibits natural tropism for dendritic
      cells and represents the prototypic infection that elicits protective CD8(+) T
      cell (cytotoxic T lymphocyte (CTL)) immunity. Here we have harnessed the
      immunobiology of this arenavirus for vaccine delivery. By using producer cells
      constitutively synthesizing the viral glycoprotein (GP), it was possible to
      replace the gene encoding LCMV GP with vaccine antigens to create replication
      defective vaccine vectors. These rLCMV vaccines elicited CTL responses that were
      equivalent to or greater than those elicited by recombinant adenovirus 5 or
      recombinant vaccinia virus in their magnitude and cytokine profiles, and they
      exhibited more effective protection in several models. In contrast to recombinant
      adenovirus 5, rLCMV failed to elicit vector-specific antibody immunity, which
      facilitated re-administration of the same vector for booster vaccination. In
      addition, rLCMV elicited T helper type 1 CD4+ T cell responses and protective
      neutralizing antibodies to vaccine antigens. These features, together with low
      seroprevalence in humans, suggest that rLCMV may show utility as a vaccine
      platform against infectious diseases and cancer.

PMID- 20139994
TI  - Poststroke dementia--what's in a name?

PMID- 20139995
TI  - Delays in the timely diagnosis of stroke in children.

PMID- 20139996
TI  - The clinical use of structural MRI in Alzheimer disease.
AB  - Structural imaging based on magnetic resonance is an integral part of the
      clinical assessment of patients with suspected Alzheimer dementia. Prospective
      data on the natural history of change in structural markers from preclinical to
      overt stages of Alzheimer disease are radically changing how the disease is
      conceptualized, and will influence its future diagnosis and treatment. Atrophy of
      medial temporal structures is now considered to be a valid diagnostic marker at
      the mild cognitive impairment stage. Structural imaging is also included in
      diagnostic criteria for the most prevalent non-Alzheimer dementias, reflecting
      its value in differential diagnosis. In addition, rates of whole-brain and
      hippocampal atrophy are sensitive markers of neurodegeneration, and are
      increasingly used as outcome measures in trials of potentially disease-modifying
      therapies. Large multicenter studies are currently investigating the value of
      other imaging and nonimaging markers as adjuncts to clinical assessment in
      diagnosis and monitoring of progression. The utility of structural imaging and
      other markers will be increased by standardization of acquisition and analysis
      methods, and by development of robust algorithms for automated assessment.

PMID- 20139997
TI  - The use of PET in Alzheimer disease.
AB  - In Alzheimer disease (AD), which is the most common cause of dementia, the
      underlying disease pathology most probably precedes the onset of cognitive
      symptoms by many years. Thus, efforts are underway to find early diagnostic
      markers as well as disease-modifying treatments for this disorder. PET enables
      various brain systems to be monitored in living individuals. In patients with AD,
      PET can be used to investigate changes in cerebral glucose metabolism, various
      neurotransmitter systems, neuroinflammation, and the protein aggregates that are
      characteristic of the disease, notably the amyloid deposits. These investigations
      are helping to further our understanding of the complex pathophysiological
      mechanisms that underlie AD, as well as aiding the early and differential
      diagnosis of the disease in the clinic. In the future, PET studies will also be
      useful for identifying new therapeutic targets and monitoring treatment outcomes.
      Amyloid imaging could be useful as early diagnostic marker of AD and for
      selecting patients for anti-amyloid-beta therapy, while cerebral glucose
      metabolism could be a suitable PET marker for monitoring disease progression. For
      the near future, multitracer PET studies are unlikely to be used routinely in the
      clinic for AD, being both burdensome and expensive; however, such studies are
      very informative in a research context.

PMID- 20139998
TI  - Primary progressive aphasia: clinicopathological correlations.
AB  - Primary progressive aphasia (PPA) is a disorder of declining language that is a
      frequent presentation of neurodegenerative diseases such as frontotemporal lobar
      degeneration. Three variants of PPA are recognized: progressive nonfluent
      aphasia, semantic dementia, and logopenic progressive aphasia. In an era of
      etiology-specific treatments for neurodegenerative conditions, determining the
      histopathological basis of PPA is crucial. Clinicopathological correlations in
      PPA emphasize the contributory role of dementia with Pick bodies and other
      tauopathies, TDP-43 proteinopathies, and Alzheimer disease. These data suggest an
      association between a specific PPA variant and an underlying pathology, although
      many cases of PPA are associated with an unexpected pathology. Neuroimaging and
      biofluid biomarkers are now emerging as important adjuncts to clinical diagnosis.
      There is great hope that the addition of biomarker assessments to careful
      clinical examination will enable accurate diagnosis of the pathology associated
      with PPA during a patient's life, and that such findings will serve as the basis
      for clinical trials in this spectrum of disease.

PMID- 20139999
TI  - The secretases: enzymes with therapeutic potential in Alzheimer disease.
AB  - The amyloid hypothesis has yielded a series of well-validated candidate drug
      targets with potential for the treatment of Alzheimer disease (AD). Three
      proteases that are involved in the processing of amyloid precursor protein-alpha
      secretase, beta-secretase and gamma-secretase-are of particular interest as they
      are central to the generation and modulation of amyloid-beta peptide and can be
      targeted by small compounds in vitro and in vivo. Given that these proteases also
      fulfill other important biological roles, inhibiting their activity will clearly
      be inherently associated with mechanism-based toxicity. Carefully determining a
      suitable therapeutic window and optimizing the selectivity of the drug treatments
      towards amyloid precursor protein processing might be ways of overcoming this
      potential complication. Secretase inhibitors are likely to be the first small
      molecule therapies aimed at AD modification that will be fully tested in the
      clinic. Success or failure of these first-generation AD therapies will have
      enormous consequences for further drug development efforts for AD and possibly
      other neurodegenerative conditions.

PMID- 20140000
TI  - Can Alzheimer disease be prevented by amyloid-beta immunotherapy?
AB  - Alzheimer disease (AD) is the most common form of dementia. The amyloid-beta
      (Abeta) peptide has become a major therapeutic target in AD on the basis of
      pathological, biochemical and genetic evidence that supports a role for this
      molecule in the disease process. Active and passive Abeta immunotherapies have
      been shown to lower cerebral Abeta levels and improve cognition in animal models
      of AD. In humans, dosing in the phase II clinical trial of the AN1792 Abeta
      vaccine was stopped when approximately 6% of the immunized patients developed
      meningoencephalitis. However, some plaque clearance and modest clinical
      improvements were observed in patients following immunization. As a result of
      this study, at least seven passive Abeta immunotherapies are now in clinical
      trials in patients with mild to moderate AD. Several second-generation active
      Abeta vaccines are also in early clinical trials. On the basis of preclinical
      studies and the limited data from clinical trials, Abeta immunotherapy might be
      most effective in preventing or slowing the progression of AD when patients are
      immunized before or in the very earliest stages of disease onset. Biomarkers for
      AD and imaging technology have improved greatly over the past 10 years and, in
      the future, might be used to identify presymptomatic, at-risk individuals who
      might benefit from Abeta immunization.

PMID- 20140002
TI  - Differential binding of bispyridinium oxime drugs with acetylcholinesterase.
AB  - AIM: To performe a time-dependent topographical delineation of protein-drug
      interactions to gain molecular insight into the supremacy of Ortho-7 over HI-6 in
      reactivating tabun-conjugated mouse acetylcholinesterase (mAChE). METHODS: We
      conducted all-atom steered molecular dynamics simulations of the two protein-drug
      complexes. Through a host of protein-drug interaction parameters (rupture force
      profiles, hydrogen bonds, water bridges, hydrophobic interactions), geometrical,
      and orientation ordering of the drugs, we monitored the enzyme's response during
      the release of the drugs from its active-site. RESULTS: The results show the
      preferential binding of the drugs with the enzyme. The pyridinium ring of HI-6
      shows excellent complementary binding with the peripheral anionic site, whereas
      one of two identical pyridinium rings of Ortho-7 has excellent binding
      compatibility in the enzyme active-site where it can orchestrate the reactivation
      process. We found that the active pyridinium ring of HI-6 undergoes a complete
      turn along the active site axis, directed away from the active-site region during
      the course of the simulation. CONCLUSION: Due to excellent cooperative binding of
      Ortho-7, as rendered by several cation-pi interactions with the active-site gorge
      of the enzyme, Ortho-7 may be a more efficient reactivator than HI-6. Our work
      supports the growing body of evidence that the efficacy of the drugs is due to
      the differential bindings of the oximes with AChE and can aid to the rational
      design of oxime drugs.

PMID- 20140003
TI  - Point-of-care test of heart-type fatty acid-binding protein for the diagnosis of
      early acute myocardial infarction.
AB  - AIM: To investigate the efficacies of point-of-care test of heart-type fatty-acid
      binding protein (H-FABP) and its combinations with the conventional biomarkers in
      the diagnosis of early acute myocardial infarction (AMI). METHODS: 227 patients
      suspected of AMI were consecutively recruited in two centers. Biomarkers
      including H-FABP, myoglobin (MYO), creatine kinase-myocardial band (CK-MB) and
      cardiac troponin T (cTnT) were determined simultaneously at admission. AMI was
      defined according to the universal definition of myocardial infarction. Chi
      Square test was adopted for the analysis. RESULTS: In patients presenting within
      12 h of symptom onset, the sensitivity of H-FABP[93.0% (95% CI: 86.6%-96.9%)] was
      significantly higher than that of initial CK-MB [67.5% (95% CI: 58.1%-76.0%),
      P<0.0001], cTnT [69.3% (95%CI: 60.0%-77.6%), P<0.0001] and MYO [68.6% (95% CI:
      54.1%-80.9%), P<0.05]. The negative predictive value of H-FABP [92.8% (95%CI:
      86.3%-96.8%)] was significantly higher than that of initial CK-MB [74.7% (95% CI:
      66.8%-81.5%), P<0.001] and cTnT [75.9% (95% CI: 68.1%-82.6%), P<0.001]. The
      sensitivity of H-FABP+cTnT combination [94.7% (95% CI: 88.9%-98.0%)] was
      significantly higher than that of admission cTnT [69.3% (95% CI: 60.0%-77.6%),
      P<0.0001], CK-MB+cTnT [75.4% (95% CI: 66.5%-83.0%), P<0.0001] and MYO+CK-MB+cTnT
      [74.5% (95% CI: 60.4%-85.7%), P<0.05]. The negative predictive value of H
      FABP+cTnT [94.5% (95% CI: 88.4%-98.0%] was significantly higher than that of
      initial cTnT [75.9% (95% CI: 68.1%-82.6%), P<0.001] and CK-MB+cTnT [79.1% (95%
      CI: 71.2%-85.6%), P<0.001]. Subgroup analysis showed that the superiorities of
      both the sensitivities and the negative predictive values of H-FABP and H
      FABP+cTnT combination occurred only in patients who presented within 6 h of the
      symptom onset. CONCLUSION: Point-of-care test of H-FABP can be used as a valuable
      biomarker to detect or exclude an early-stage AMI. Combining H-FABP and cTnT
      provides the best performance for early AMI diagnosis.

PMID- 20140004
TI  - Lack of effect of genetic polymorphisms of SLCO1B1 on the lipid-lowering response
      to pitavastatin in Chinese patients.
AB  - AIM: To investigate the SLCO1B1 388A>G and 521T>C polymorphisms in hyperlipidemia
      patients and evaluate the effect of the two polymorphisms on the lipid-lowering
      efficacy of pitavastatin. METHODS: The functional polymorphisms of SLCO1B1
      (388A>G and 521T>C) were genotyped in 140 Chinese patients with essential
      hyperlipidemia using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and one-step tetra-primers ARMS-PCR. Eighty-five patients
      were enrolled in the clinical trial and given 2 mg of pitavastatin daily for 8
      weeks. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL),
      and low-density lipoprotein (LDL) serum levels were measured at baseline, after 4
      weeks and after 8 weeks of treatment. RESULTS: The allele frequencies of SLCO1B1
      388A>G and 521T>C in essential hyperlipidemia patients were 71.1% and 11.1%,
      respectively. The 4- and 8-week treatment with pitavastatin significantly reduced
      TC, TG, and LDL levels, but there was no statistical difference among patients
      with wild type, SLCO1B1 388A>G or SLCO1B1 521T>C in the lipid-lowering efficacy
      of pitavastatin. CONCLUSION: The present study found that the allele frequencies
      of SLCO1B1 388A>G and 521T>C in Chinese patients with essential hyperlipidemia
      are comparable to those in healthy Chinese population. SLCO1B1 388A>G and 521T>C
      do not affect the lipid-lowering efficacy of pitavastatin.

PMID- 20140005
TI  - Protective effects of ginsenoside Rb(3) on oxygen and glucose deprivation-induced
      ischemic injury in PC12 cells.
AB  - AIM: To investigate the protective effects of ginsenoside Rb(3), a triterpenoid
      saponin isolated from the leaves of Panax notoginseng, on ischemic and
      reperfusion injury model of PC12 cells and elucidate the related mechanisms.
      METHODS: PC12 cells exposed to oxygen and glucose deprivation (OGD) and
      restoration (OGD-Rep) were used as an in vitro model of ischemia and reperfusion.
      3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and
      lactate dehydrogenase (LDH) leakage were used to evaluate the protective effects
      of ginsenoside Rb(3). Cellular apoptosis and mitochondrial membrane potential
      (MMP) were analyzed using flow cytometry. Intracellular calcium ion concentration
      ([Ca(2+)](i)) was detected using fluorophotometer system. Caspase-3, -8, and -9
      activities were measured using assay kits with an ELISA reader. Western blotting
      assay was used to evaluate the release of cytochrome c and expression of caspase
      3, Bcl-2 and Bax proteins. RESULTS: It was shown that ginsenoside Rb(3) (0.1-10
      micromol/L) significantly increased cell viability and inhibited LDH release in a
      dose-dependent manner on the ischemic model. In addition, ginsenoside Rb(3) also
      significantly inhibited ischemic injury-induced apoptosis, [Ca(2+)](i) elevation,
      and decrease of MMP. Meanwhile, pretreatment with ginsenoside Rb(3) significantly
      induced an increase of Bcl-2 protein expression and a decrease of cytosolic
      cytochrome c, cleaved-caspase 3 and Bax protein expression, the caspase-3, -8,
      and -9 activity were also inhibited. CONCLUSION: The results indicated that
      ginsenoside Rb(3) could markedly protected OGD-Rep induced ischemic injury and
      the mechanisms maybe related to its suppression of the intracellular Ca(2+)
      elevation and inhibition of apoptosis and caspase activity. Ginsenoside Rb(3)
      could be a promising candidate in the development of a novel class of anti
      ischemic agent.

PMID- 20140006
TI  - Blockade of CD28 by a synthetical peptoid inhibits T-cell proliferation and
      attenuates graft-versus-host disease.
AB  - CD28 is one of the costimulatory molecules crucial for T-cell activation and thus
      has become an attractive target for therapeutic immunomodulation. Conventional
      strategies for blocking CD28 activity using monoclonal antibodies, Fab fragments,
      antagonistic peptide and fusion proteins, have apparent disadvantages such as
      inherent immunogenicity, unwanted Fc signaling, poor tissue penetration and
      bioinstability. Recent research has been directed toward the creation of non
      natural, sequence-specific biomimetic oligomers with bioinspired structures that
      capture the amino-acid interface of the targeted proteins. One such family of
      molecules is the poly-N-substituted glycines or peptoids, which have close
      structural similarity to peptides but are essentially invulnerable to protease
      degradation. To screen for peptoids that specifically target CD28, we first
      designed and chemically synthesized 19 candidate peptoids based on molecular
      modeling and docking. Using the phage-displaying system that expresses the
      extracellular domain of the CD28 homodimer and contains the core B7-binding
      motif, a peptoid (No. 9) with a molecular formula of C(21)H(29)N(3)O(7), was
      identified to display the highest binding activity to CD28. This peptoid not only
      inhibited the lymphocyte proliferation in vitro, but suppressed immunoresponses
      against alloantigens in vivo, and attenuated the graft-versus-host disease in a
      mouse bone-marrow transplantation model. These results suggested that peptoids
      targeting CD28 are effective agents for blocking the CD28-mediated costimulation
      and suitable for development of novel therapeutic approaches for diseases
      involving this pathway.

PMID- 20140007
TI  - Epigallocatechin-3-gallate (EGCG) attenuates inflammation in MRL/lpr mouse
      mesangial cells.
AB  - Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been
      reported to exert anti-inflammatory effects on immune cells. EGCG is also shown
      to activate the metabolic regulator, adenosine 5'-monophosphate-activated protein
      kinase (AMPK). Reports have also indicated that EGCG inhibits the immune
      stimulated phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin
      (mTOR) pathway. The PI3K/Akt/mTOR pathway has been implicated in mesangial cell
      activation in lupus. Mesangial cells from MRL/lpr lupus-like mice are hyper
      responsive to immune stimulation and overproduce nitric oxide (NO) and other
      inflammatory mediators when stimulated. In our current studies, we sought to
      determine the mechanism by which EGCG attenuates immune-induced expression of pro
      inflammatory mediators. Cultured mesangial cells from MRL/lpr mice were pre
      treated with various concentrations of EGCG and stimulated with
      lipopolysaccharide (LPS)/interferon (IFN)-gamma. EGCG activated AMPK and blocked
      LPS/IFN-gamma-induced inflammatory mediator production (iNOS expression,
      supernatant NO and interleukin-6). Interestingly, EGCG attenuated inflammation
      during AMPK inhibition indicating that the anti-inflammatory effect of EGCG may
      be partially independent of AMPK activation. Furthermore, we found that EGCG
      effectively inhibited the immune-stimulated PI3K/Akt/mTOR pathway independently
      of AMPK, by decreasing phosphorylation of Akt, suggesting an alternate mechanism
      for EGCG-mediated anti-inflammatory action in mesangial cells. Taken together,
      these studies show that EGCG attenuated inflammation in MRL/lpr mouse mesangial
      cells via the PI3K/Akt/mTOR pathway. Our findings suggest a potential therapeutic
      role for the use of EGCG to regulate inflammation and control autoimmune disease.

PMID- 20140008
TI  - Role of activating transcription factor 3 (ATF3) in sublytic C5b-9-induced
      glomerular mesangial cell apoptosis.
AB  - Sublytic complement C5b-9 complexes can cause cell apoptosis, but the mechanism
      of glomerular mesangial cell (GMC) apoptosis mediated by these complexes has not
      been well defined. The activating transcription factor 3 (ATF3) gene is an
      immediate early gene for the cell to cope with a variety of stress signals and
      can promote apoptosis of some cells. In this study, ATF3 expression and cell
      apoptosis in GMCs induced by sublytic C5b-9 were measured, and then the effects
      of ATF3 gene over-expression or knockdown on GMC apoptosis induced by sublytic
      C5b-9 were examined at a fixed time. The results showed that both ATF3 expression
      and GMC apoptosis were markedly increased and ATF3 over-expression obviously
      increased sublytic C5b-9-induced GMC apoptosis, whereas ATF3 gene silencing had a
      significant opposite effect. Collectively, these findings indicate that
      upregulation of ATF3 gene expression is involved in regulating GMC apoptosis
      induced by sublytic C5b-9 complexes.

PMID- 20140009
TI  - Premetastatic milieu explained by TLR4 agonist-mediated homeostatic inflammation.
AB  - Accumulating evidence suggests that Toll-like receptor 4 (TLR4), a sensor for
      danger signals, is expressed not only in immune cells, but also in resident
      epithelial cells, and appears to participate in tissue homeostasis. To explain
      the premetastatic microenvironment created by the newly discovered endogenous
      TLR4 ligands, I propose a hypothesis of homeostatic inflammation that includes
      the classical danger hypothesis.

PMID- 20140010
TI  - Enhancement of antitumor immunity by low-dose total body irradiationis associated
      with selectively decreasing the proportion and number of T regulatory cells.
AB  - Low-dose total body irradiation (LTBI) is used in the treatment of some cancers
      mainly for immune enhancement rather than cell killing. However, the mechanism
      underlying LTBI remains unknown. In this study, by analyzing the immune patterns
      of lymphocytes, we found that the percentage and absolute number of
      CD4(+)CD25(+)Foxp3(+) regulatory T cells are markedly decreased in naive mice
      following treatment with LTBI. On the contrary, the CD4(+)CD44(+)/CD8(+)CD44(+)
      effect or-memory T cells are greatly increased. Importantly, naive mice treated
      with dendritic cell-gp 100 tumor vaccines under LTBI induced an enhancement of
      antigen-specific proliferation and cytotoxicity as well as interferon-gamma (IFN
      gamma) secretion against F10 melanoma tumor challenge, compared to treatment with
      either the tumor vaccine or LTBI alone. Consequently, the treatment resulted in a
      reduced tumor burden and prolonged mouse survival. Our data demonstrate that
      LTBI's enhancement of antitumor immunity was mainly associated with selectively
      decreasing the proportion and number of T regulatory cells,implying the potential
      application of the combination of LTBI and a tumor vaccine in antitumor therapy.

PMID- 20140011
TI  - Increased expression of human T-cell immunoglobulin- and mucin-domain-containing
      molecule-4 in peripheral blood mononuclear cells from patients with system lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease. Innate and
      adaptive immunity cooperatively contribute to the development of SLE. Antigen
      presenting cells (APCs) have been suggested to link innate and adaptive immunity.
      T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4; also known
      as Timd4), expressed primarily on the surface of APCs, is a member of the TIM
      family, a recently described group of molecules that have received much attention
      as potential regulators of the immune system. In this study, we used quantitative
      real-time reverse transcription-polymerase chain reaction to examine the mRNA
      expression of Tim-4 in peripheral blood mononuclear cells (PBMCs) from SLE
      patients and further analyzed the correlation between the expression of Tim-4 and
      Tim-1 (a potential ligand for Tim-4) in PBMCs and serum tumor necrosis factor
      (TNF)-alpha levels. The results showed that Tim-4 mRNA expression in PBMCs was
      significantly higher in SLE patients than in healthy controls, especially those
      patients in the active phase of disease. Moreover, Tim-4 mRNA levels were closely
      correlated with Tim-1 mRNA levels in PBMCs and with serum TNF-alpha levels in SLE
      patients but not in the control group. Taken together, these results demonstrate
      that Tim-4 may be involved in the pathogenesis of SLE.

PMID- 20140013
TI  - VAV2 regulates epidermal growth factor receptor endocytosis and degradation.
AB  - Vav proteins are guanine nucleotide exchange factors for Rho GTPases that
      regulate cell adhesion, motility, spreading and proliferation in response to
      growth factor signalling. In this work, we show that Vav2 expression delayed
      epidermal growth factor receptor (EGFR) internalization and degradation, and
      enhanced EGFR, ERK and Akt phosphorylations. This effect of Vav2 on EGFR
      degradation is dependent on its guanine nucleotide exchange function. Knockdown
      of Vav2 in HeLa cells enhanced EGFR degradation and reduced cell proliferation.
      epidermal growth factor stimulation led to co-localization of Vav2 with EGFR and
      Rab5 in endosomes. We further show that the effect of Vav2 on EGFR stability is
      modulated by its interaction with two endosome-associated proteins and require
      RhoA function. Thus, in this work, we report for the first time that Vav2 can
      regulate growth factors receptor signalling by slowing receptor internalization
      and degradation through its interaction with endosome-associated proteins.

PMID- 20140012
TI  - Flanking sequence specificity determines coding microsatellite heteroduplex and
      mutation rates with defective DNA mismatch repair (MMR).
AB  - The activin type II receptor (ACVR2) contains two identical microsatellites in
      exons 3 and 10, but only the exon 10 microsatellite is frameshifted in mismatch
      repair (MMR)-defective colonic tumors. The reason for this selectivity is not
      known. We hypothesized that ACVR2 frameshifts were influenced by DNA sequences
      surrounding the microsatellite. We constructed plasmids in which exons 3 or 10 of
      ACVR2 were cloned +1 bp out of frame of enhanced green fluorescent protein
      (EGFP), allowing -1 bp frameshift to express EGFP. Plasmids were stably
      transfected into MMR-deficient cells, and subsequent non-fluorescent cells were
      sorted, cultured and harvested for mutation analysis. We swapped DNA sequences
      flanking the exon 3 and 10 microsatellites to test our hypothesis. Native ACVR2
      exon 3 and 10 microsatellites underwent heteroduplex formation (A(7)/T(8)) in
      hMLH1(-/-) cells, but only exon 10 microsatellites fully mutated (A(7)/T(7)) in
      both hMLH1(-/-) and hMSH6(-/-) backgrounds, showing selectivity for exon 10
      frameshifts and inability of exon 3 heteroduplexes to fully mutate. Substituting
      nucleotides flanking the exon 3 microsatellite for nucleotides flanking the exon
      10 microsatellite significantly reduced heteroduplex and full mutation in hMLH1(
      /-) cells. When the exon 3 microsatellite was flanked by nucleotides normally
      surrounding the exon 10 microsatellite, fully mutant exon 3 frameshifts appeared.
      Mutation selectivity for ACVR2 lies partly with flanking nucleotides surrounding
      each microsatellite.

PMID- 20140014
TI  - Molecular basis of S100 proteins interacting with the p53 homologs p63 and p73.
AB  - S100 proteins modulate p53 activity by interacting with its tetramerization
      (p53TET, residues 325-355) and transactivation (residues 1-57) domains. In this
      study, we characterized biophysically the binding of S100A1, S100A2, S100A4,
      S100A6 and S100B to homologous domains of p63 and p73 in vitro by fluorescence
      anisotropy, analytical ultracentrifugation and analytical gel filtration. We
      found that S100A1, S100A2, S100A4, S100A6 and S100B proteins bound different p63
      and p73 tetramerization domain variants and naturally occurring isoforms with
      varying affinities in a calcium-dependent manner. Additional interactions were
      observed with peptides derived from the p63 and p73 N-terminal transactivation
      domains. Importantly, S100 proteins bound p63 and p73 with different affinities
      in their different oligomeric states, similarly to the differential modes of
      binding to p53. On the basis of our data, we hypothesize that S100 proteins
      regulate the oligomerization state of all three p53 family members and their
      isoforms, with a potential physiological relevance in developmental and disease
      related processes. The regulation of the p53 family by S100 is complicated and
      depends on the target preference of each individual S100 protein, the
      concentration of the proteins and calcium, as well as the splicing variation of
      p63 or p73. Our results outlining the complexity of the interaction should be
      considered when studying the functional effects of S100 proteins in their
      biological context.

PMID- 20140015
TI  - Peptide-based interference of the transmembrane domain of neuropilin-1 inhibits
      glioma growth in vivo.
AB  - Angiogenesis in glioblastoma is largely dependent on vascular endothelial growth
      factor (VEGF) signalling. Consistently, the VEGF coreceptor NRP1 promotes
      angiogenesis and tumour growth in gliomas. Here, we provide data showing that an
      innovative peptidic tool targeting the transmembrane domain of NRP1 efficiently
      blocks rat and human glioma growth in vivo. We show both in vivo and in vitro
      that the antitumour effect results from the anti-proliferative, anti-migratory
      and anti-angiogenic properties of the compound. The proposed NRP1 antagonizing
      peptide is therefore a promising novel class of anti-angiogenic drugs that might
      prolong glioma patient survival. Our results finally show for the first time that
      the transmembrane domain of important signalling receptors can be antagonized in
      vivo thereby providing a new avenue towards the development of atypical
      antagonists with strong therapeutic potential.

PMID- 20140016
TI  - Pim1 kinase synergizes with c-MYC to induce advanced prostate carcinoma.
AB  - The oncogenic PIM1 kinase has been implicated as a cofactor for c-MYC in prostate
      carcinogenesis. In this study, we show that in human prostate tumors,
      coexpression of c-MYC and PIM1 is associated with higher Gleason grades. Using a
      tissue recombination model coupled with lentiviral-mediated gene transfer we find
      that Pim1 is weakly oncogenic in naive adult mouse prostatic epithelium. However,
      it cooperates dramatically with c-MYC to induce prostate cancer within 6-weeks.
      Importantly, c-MYC/Pim1 synergy is critically dependent on Pim1 kinase activity.
      c-MYC/Pim1 tumors showed increased levels of the active serine-62 (S62)
      phosphorylated form of c-MYC. Grafts expressing a phosphomimetic c-MYCS62D mutant
      had higher rates of proliferation than grafts expressing wild type c-MYC but did
      not form tumors like c-MYC/Pim1 grafts, indicating that Pim1 cooperativity with c
      MYC in vivo involves additional mechanisms other than enhancement of c-MYC
      activity by S62 phosphorylation. c-MYC/Pim1-induced prostate carcinomas show
      evidence of neuroendocrine (NE) differentiation. Additional studies, including
      the identification of tumor cells coexpressing androgen receptor and NE cell
      markers synaptophysin and Ascl1 suggested that NE tumors arose from
      adenocarcinoma cells through transdifferentiation. These results directly show
      functional cooperativity between c-MYC and PIM1 in prostate tumorigenesis in vivo
      and support efforts for targeting PIM1 in prostate cancer.

PMID- 20140017
TI  - Activating ROCK1 somatic mutations in human cancer.
AB  - Cancer cells acquire characteristics of deregulated growth, survival and
      increased metastatic potential. Genetic mutations that provide a selective
      advantage by promoting these characteristics have been termed 'drivers,' whereas
      mutations that do not contribute to disease initiation/progression are termed
      'passengers.' The advent of high-throughput methodologies has facilitated large
      scale screening of cancer genomes and the subsequent identification of novel
      somatic mutations. Although this approach has generated valuable results, the
      data remain incomplete until the functional consequences of these mutations are
      determined to differentiate potential drivers from passengers. ROCK1 is an
      essential effector kinase downstream of Rho GTPases, an important pathway
      involved in cell migration. The Cancer Genome Project identified three
      nonsynonymous mutations in the ROCK1 gene. We now show that these somatic ROCK1
      mutations lead to elevated kinase activity and drive actin cytoskeleton
      rearrangements that promote increased motility and decreased adhesion,
      characteristics of cancer progression. Mapping of the kinase-interacting regions
      of the carboxy terminus combined with structural modeling provides an insight
      into how these mutations likely affect the regulation of ROCK1. Consistent with
      the frequency of ROCK1 mutations in human cancer, these results support the
      conclusion that there is selective pressure for the ROCK1 gene to acquire
      'driver' mutations that result in kinase activation.

PMID- 20140018
TI  - Lysine methylation regulates the pRb tumour suppressor protein.
AB  - The pRb tumour suppressor protein has a central role in coordinating early cell
      cycle progression. An important level of control imposed on pRb occurs through
      post-translational modification, for example, phosphorylation. We describe here a
      new level of regulation on pRb, mediated through the targeted methylation of
      lysine residues, by the methyltransferase Set7/9. Set7/9 methylates the C
      terminal region of pRb, both in vitro and in cells, and methylated pRb interacts
      with heterochromatin protein HP1. pRb methylation is required for pRb-dependent
      cell cycle arrest and transcriptional repression, as well as pRb-dependent
      differentiation. Our results indicate that methylation can influence the
      properties of pRb, and raise the interesting possibility that methylation
      modulates pRb tumour suppressor activity.

PMID- 20140019
TI  - Interleukin-6 induces increased motility, cell-cell and cell-substrate dyshesion
      and epithelial-to-mesenchymal transformation in breast cancer cells.

PMID- 20140020
TI  - Role of Mdm4 in drug sensitivity of breast cancer cells.
AB  - The p53 tumor suppressor protein is frequently mutated in human tumors. It is
      thought that the p53 pathway is indirectly impaired in the remaining tumors, for
      example by overexpression of its important regulators Mdm2 and Mdm4, making them
      attractive targets for the development of anti-cancer agents. Recent studies have
      suggested that Mdm4 levels determine the sensitivity of tumor cells for anti
      cancer therapy. To investigate this possibility, we studied the drug sensitivity
      of several breast cancer cell lines containing wild-type p53, but expressing
      different Mdm4 levels. We show that endogenous Mdm4 levels can affect the
      sensitivity of breast cancer cells to anti-cancer agents, but in a cell line
      dependent manner and depending on an intact apoptotic response. Furthermore,
      treatment with the non-genotoxic agent Nutlin-3 sensitizes cells for doxorubicin,
      showing that activation of p53 by targeting its regulators is an efficient
      strategy to decrease cell viability of breast cancer cells. These results confirm
      a function of Mdm4 in determining the efficacy of chemotherapeutic agents to
      induce apoptosis of cancer cells in a p53-dependent manner, although additional
      undetermined factors also influence the drug response. Targeting Mdm4 to
      sensitize tumor cells for chemotherapeutic drugs might be a strategy to
      effectively treat tumors harboring wild-type p53.

PMID- 20140021
TI  - Myc heterozygosity attenuates the phenotypes of APC deficiency in the small
      intestine.
AB  - The adenomatous polyposis coli (APC) gene encodes APC tumour suppressor protein,
      germline mutation of which causes familial adenomatous polyposis, an autosomal
      intestinal cancer syndrome. We have previously demonstrated that the proto
      oncogene c-Myc is essential for all the phenotypes that occur after APC loss in
      the murine small intestine. One caveat to this study is that it was performed in
      the complete absence of c-Myc. In this study, we show that heterozygosity for Myc
      reduces the phenotypes of APC loss and Wnt target gene expression and slows
      tumourigenesis. Crucially, the levels of Myc are twofold higher than wild-type
      levels showing that the level of Myc induced by Wnt signalling is absolutely
      vital for the fate of APC-deficient cells. Taken together, this suggests that c
      Myc inhibition may be a viable chemoprevention strategy for colorectal cancer.

PMID- 20140022
TI  - Differential chemokine expression in chronic GVHD of the conjunctiva.
AB  - In chronic GVHD after BMT, the conjunctiva represents a target organ. GVHD can
      lead to severe inflammation and dry-eye syndrome (sicca syndrome). The molecular
      mechanisms are largely unknown. We examined the expression of chemokines in the
      conjunctiva in cases of chronic GVHD. In this study, we included 10 patients with
      chronic GVHD and 10 healthy controls. Clinical data were collected and tear film
      analysis and conjunctival cytology were carried out. Conjunctival biopsies were
      taken from all participants. Gene expression profiles of chemokines and their
      corresponding receptors were evaluated by means of quantitative real-time PCR.
      Chemokine protein expression was analysed by immunohistochemical analyses.
      Expressions of the Th1-associated chemokines, chemokine (C-X-C motif) ligand
      (CXCL) 9 (Mig), CXCL10 (IP-10), and their receptor chemokine (C-X-C motif)
      receptor 3 (CXCR3) were significantly increased in GVHD patients.
      Immunohistochemical analysis confirmed marked expression of the inflammatory
      CXCR3 ligands. A total of six patients had a moderate or severe sicca syndrome.
      Impression cytology revealed a mild keratinisation, moderate keratinisation or
      severe squamous metaplasia in three patients, respectively. Chronic GVHD of the
      conjunctiva is characterised by the expression of Th1-associated chemokines.
      Taken together, our results confirm that the conjunctiva is a target organ in
      this T cell-mediated process and add to molecular understanding of conjunctival
      GVHD.

PMID- 20140023
TI  - Focal nodular hyperplasia in pediatric allogeneic hematopoietic cell transplant:
      case series.

PMID- 20140024
TI  - MTX or mycophenolate mofetil with CsA as GVHD prophylaxis after reduced-intensity
      conditioning PBSCT from HLA-identical siblings.
AB  - Mycophenolate mofetil (MMF) in combination with CsA seems to lead to earlier post
      transplant hematological recovery and less mucositis than MTX, with a similar
      incidence of GVHD. In this study we analyzed the post transplant outcomes of two
      cohorts of patients who underwent an HLA-identical sibling reduced intensity
      conditioning transplantation (allo-RIC) with GVHD prophylaxis consisting of CsA
      in combination with either MMF or a short course of MTX. We included 145
      consecutive allo-RIC transplants performed between April 2000 and August 2007.
      The median follow-up for survivors was 41 months (4-105 months). The study group
      included 91 males. Median age was 55 years (range 18-71 years). Diagnoses
      included myeloid (n=65) and lymphoid (n=80) malignancies. GVHD prophylaxis
      consisted of CsA/MMF in 52 and CsA/MTX in 93 patients. The conditioning regimen
      was based on fludarabine in combination with BU (n=59) or melphalan (n=86). The
      occurrence of grade 2-4 mucositis was higher in the CsA/MTX group than in the
      CsA/MMF group (57 vs 23%, P=0.001). The cumulative incidence of acute and chronic
      GVHD was similar, 48 vs 50% and 71 vs 68%, respectively (P>0.7). The 2-year
      relapse and OS were similar in the CsA/MTX and CsA/MMF groups (29 vs 21%, P=0.3
      and 52 vs 51%, P=0.7, respectively). Our results support further prospective
      studies comparing the use of the CsA/MMF combination with CsA/MTX as GVHD
      prophylaxis in HLA-identical sibling donor allo-RIC recipients.

PMID- 20140027
TI  - Translational control in the C. elegans hermaphrodite germ line.
AB  - The formation of a fully developed gamete from an undifferentiated germ cell
      requires progression through numerous developmental stages and cell fate
      decisions. The precise timing and level of gene expression guides cells through
      these stages. Translational regulation is highly utilized in the germ line of
      many species, including Caenorhabditis elegans, to regulate gene expression and
      ensure the proper formation of gametes. In this review, we discuss some of the
      developmental stages and cell fate decisions involved in the formation of
      functional gametes in the C. elegans germ line in which translational control has
      been implicated. These stages include the mitosis versus meiosis decision, the
      sperm/oocyte decision, and gamete maturation. We also discuss some of the
      techniques used to identify mRNA targets; the identification of these targets is
      necessary to clearly understand the role each RNA-binding protein plays in these
      decisions. Relatively few mRNA targets have been identified, thus providing a
      major focus for future research. Finally, we propose some reasons why
      translational control may be utilized so heavily in the germ line. Given that
      many species have this substantial reliance on translational regulation for the
      control of gene expression in the germ line, an understanding of translational
      regulation in the C. elegans germ line is likely to increase our understanding of
      gamete formation in general.

PMID- 20140028
TI  - Comparison of the chromosome maps around a resistance hot spot on chromosome 5 of
      potato and tomato using BAC-FISH painting.
AB  - Potato chromosome 5 harbours numerous genes for important qualitative and
      quantitative traits, such as resistance to the root cyst nematode Globodera
      pallida and the late blight fungus, Phytophthora infestans. The genes make up
      part of a "hot spot" for resistances to various pathogens covering a genetic map
      length of 3 cM between markers GP21 and GP179. We established the physical size
      and position of this region on chromosome 5 in potato and tomato using
      fluorescence in situ hybridization (FISH) on pachytene chromosomes. Five potato
      bacterial artificial chromosome (BAC) clones with the genetically anchored
      markers GP21, R1-contig (proximal end), CosA, GP179, and StPto were selected,
      labeled with different fluorophores, and hybridized in a five-colour FISH
      experiment. Our results showed the location of the BAC clones in the middle of
      the long arm of chromosome 5 in both potato and tomato. Based on chromosome
      measurements, we estimate the physical size of the GP21-GP179 interval at 0.85 Mb
      and 1.2 Mb in potato and tomato, respectively. The GP21-GP179 interval is part of
      a genome segment known to have inverted map positions between potato and tomato.

PMID- 20140029
TI  - A native QTL for Fusarium head blight resistance in North American barley
      (Hordeum vulgare L.) independent of height, maturity, and spike type loci.
AB  - Fusarium head blight (FHB), caused by Fusarium graminearum Schwabe (teleomorph
      Gibberella zeae (Schwein.) Petch), is one of the major diseases of barley
      (Hordeum vulgare L.) in eastern China, the Upper Midwest of the USA, and the
      eastern Prairie Provinces of Canada. To identify quantitative trait loci (QTL)
      controlling FHB resistance, a recombinant inbred line population (F6:7) was
      developed from the cross Zhenongda 7/PI 643302. The population was phenotyped for
      resistance to FHB in two experiments in China and four experiments in North
      Dakota. Accumulation of the mycotoxin deoxynivalenol was determined in one
      experiment in China and two in North Dakota. Simplified composite interval
      mapping was performed on the whole genome level using the software MQTL. The QTL
      FHB-2 from PI 643302 for FHB resistance was found on the distal portion of
      chromosome 2HL in all six FHB screening environments. This QTL accounted for 14%
      of phenotypic variation over six environments and was not associated with heading
      date or plant height. The FHB resistance QTL FHB-2 detected near the end of
      chromosome 2HL is in a different location from those found previously and is
      therefore probably unique. Because the QTL was not contributed by the Chinese
      cultivar Zhenongda 7, it is likely a native QTL present in North American barley.
      The QTL FHB-2 represents the first reported QTL for native FHB resistance in
      North American germ plasm and has been given the provisional name Qrgz-2H-14.
      This QTL should be considered for pyramiding with other FHB QTL previously
      mapped.

PMID- 20140025
TI  - The phasevarion: phase variation of type III DNA methyltransferases controls
      coordinated switching in multiple genes.
AB  - In several host-adapted pathogens, phase variation has been found to occur in
      genes that encode methyltransferases associated with type III restriction
      modification systems. It was recently shown that in the human pathogens
      Haemophilus influenzae, Neisseria gonorrhoeae and Neisseria meningitidis phase
      variation of a type III DNA methyltransferase, encoded by members of the mod gene
      family, regulates the expression of multiple genes. This novel genetic system has
      been termed the 'phasevarion' (phase-variable regulon). The wide distribution of
      phase-variable mod family genes indicates that this may be a common strategy used
      by host-adapted bacterial pathogens to randomly switch between distinct cell
      types.

PMID- 20140030
TI  - Genetic analysis and mapping of a thermosensitive genic male sterility gene,
      tms6(t), in rice (Oryza sativa L.).
AB  - Thermosensitive genic male-sterile (TGMS) rice is widely used in hybrid rice
      production. Because of its specific temperature requirement, it can be used only
      in a narrow rice-growing zone in Asia. A newly discovered TGMS line, G20S, has an
      opposite phenotype compared with normal TGMS lines. G20S is completely sterile
      when the temperature is lower than 29.5 degrees C. Thus, it can be widely used in
      a larger area. Genetic analysis indicated that the sterility of G20S was
      controlled by a single recessive gene that was named tms6(t). An F2 population
      from the cross between G20S and Jing226 was developed and used for molecular
      mapping of the tms6(t) gene. The simple sequence repeat technique, combined with
      bulked segregant analysis, was used to screen markers linked to the target gene,
      and linkage markers such as RM216, RM2504, RM3152, and RM4455 were identified.
      These markers are all located on chromosome 10; therefore, tms6(t) was
      subsequently mapped on chromosome 10. Co-segregation analysis using the F2
      population showed that two of these markers, RM3152 and RM4455, were closely
      linked to tms6(t) at distances of 3.00 cM and 1.10 cM, respectively.
      Additionally, integration of the genetic and physical maps showed that there were
      15 BAC/PAC clones overlapping between RM3152 and RM4455, and tms6(t) was mapped
      to an interval of 1455 kb.

PMID- 20140026
TI  - Bacterial nucleoid-associated proteins, nucleoid structure and gene expression.
AB  - Emerging models of the bacterial nucleoid show that nucleoid-associated proteins
      (NAPs) and transcription contribute in combination to the dynamic nature of
      nucleoid structure. NAPs and other DNA-binding proteins that display gene
      silencing and anti-silencing activities are emerging as key antagonistic
      regulators of nucleoid structure. Furthermore, it is becoming clear that the
      boundary between NAPs and conventional transcriptional regulators is quite
      blurred and that NAPs facilitate the evolution of novel gene regulatory circuits.
      Here, NAP biology is considered from the standpoints of both gene regulation and
      nucleoid structure.

PMID- 20140031
TI  - Comparative cytogenetic analysis of Avena macrostachya and diploid C-genome Avena
      species.
AB  - The chromosome set of Avena macrostachya Balansa ex Coss. et Durieu was analyzed
      using C-banding and fluorescence in situ hybridization with 5S and 18S-5.8S-26S
      rRNA gene probes, and the results were compared with the C-genome diploid Avena
      L. species. The location of major nucleolar organizer regions and 5S rDNA sites
      on different chromosomes confirmed the affiliation of A. macrostachya with the C
      genome group. However, the symmetric karyotype, the absence of "diffuse
      heterochromatin" and the location of large C-band complexes in proximal
      chromosome regions pointed to an isolated position of A. macrostachya from other
      Avena species. Based on the distribution of rDNA loci on the C-genome chromosomes
      of diploid and polyploid Avena species, we propose a model of the chromosome
      alterations that occurred during the evolution of oat species.

PMID- 20140032
TI  - Prion protein gene (PRNP) polymorphisms in native Chinese cattle.
AB  - Polymorphisms in four regions of the bovine prion protein gene (PRNP) confer
      susceptibility to bovine spongiform encephalopathy (BSE). These polymorphisms
      include a 23-bp insertion/deletion (indel) in the promoter region, a 12-bp indel
      in intron 1, an octapeptide repeat or 24-bp indel in the open reading frame, and
      a single nucleotide polymorphism (SNP) in the coding region. In this study, we
      investigated the frequency distributions of genotypes, alleles, and haplotypes at
      these indel sites in 349 native Chinese cattle and sequence variants in 50
      samples. Our results showed that cattle in southern China have low frequencies of
      the 12-bp deletion allele and the 23-bp deletion / 12-bp deletion haplotype,
      which have been suggested to be relevant to BSE susceptibility. Interestingly, a
      significant difference was observed between BSE-affected cattle and healthy
      Chinese cattle in the 12-bp indel polymorphism. A total of 14 SNPs were
      discovered in the coding region of PRNP in Chinese cattle. Three of these SNPs
      were associated with amino acid changes (K3T, P54S, and S154N). The E211K
      substitution that was recently reported in the US atypical BSE case was not
      detected in this study.

PMID- 20140033
TI  - Production and genetic analysis of partial hybrids from intertribal sexual
      crosses between Brassica napus and Isatis indigotica and progenies.
AB  - With the dye and medicinal plant Isatis indigotica (2n = 14) as pollen parent,
      intertribal sexual hybrids with Brassica napus (2n = 38, AACC) were obtained and
      characterized. Among a lot of F1 plants produced, only five hybrids (H1-H5) were
      distinguished morphologically from female B. napus parents by showing low
      fertility and some characters of I. indigotica, and also by having different
      chromosome numbers. H1-H4 had similar but variable chromosome numbers in their
      somatic and meiotic cells (2n = 25-30), and H5 had 2n = 19, the same number as
      the haploid of B. napus. GISH analysis of the cells from H1 and H5 detected one
      I. indigotica chromosome and one or two chromosome terminal fragments. New B.
      napus types with phenotypic and genomic alterations were produced by H1 after
      pollination by B. napus and selfing for several generations, and by H5 after
      selfing. A progeny plant (2n = 20) was derived from H1 after pollination by I.
      indigotica twice and had a phenotype similar to a certain type of B. rapa,
      showing that hybrid H1 likely retained all chromosomes of the A genome and lost
      some of the C genome in parental B. napus. The reasons for the formation of the
      partial hybrids with unexpected chromosomal complements and for the chromosome
      elimination are discussed.

PMID- 20140034
TI  - Commemorating the 20th century Darwin: Ernst Mayr's words and thoughts, five
      years later. Interview by Rob J. Kulathinal.
AB  - It has been five years since Ernst Mayr, one of the most influential evolutionary
      biologists of the last century, passed away. Mayr's seminal work as a naturalist
      and, in particular, as a bird systematist allowed him to approach the species
      problem in a revolutionary way. As a leading architect of the Modern Evolutionary
      Synthesis, Mayr helped integrate Darwinian theory with the broad fields of
      systematics and genetics. We pay tribute to this legend by publishing an
      interview taken shortly before his death.

PMID- 20140035
TI  - NIH state-of-the-science conference statement: Enhancing use and quality of
      colorectal cancer screening.
AB  - OBJECTIVE: To provide health care providers, patients, and the general public
      with a responsible assessment of currently available data on enhancing use and
      quality of colorectal cancer screening. PARTICIPANTS: A non-DHHS, nonadvocate 13
      member panel representing the fields of cancer surveillance, health services
      research, community-based research, informed decision-making, access to care,
      health care policy, health communication, health economics, health disparities,
      epidemiology, statistics, thoracic radiology, internal medicine,
      gastroenterology, public health, end-of-life care, and a public representative.
      In addition, 20 experts from pertinent fields presented data to the panel and
      conference audience. EVIDENCE: Presentations by experts and a systematic review
      of the literature prepared by the RTI International-University of North Carolina
      Evidence-based Practice Center, through the Agency for Healthcare Research and
      Quality. Scientific evidence was given precedence over anecdotal experience.
      CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence
      presented in open forum and on published scientific literature. The draft
      statement was presented on the final day of the conference and circulated to the
      audience for comment. The panel released a revised statement later that day at
      http://consensus.nih.gov. This statement is an independent report of the panel
      and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS:
      The panel found that despite substantial progress toward higher colorectal cancer
      screening rates nationally, screening rates fall short of desirable levels.
      Targeted initiatives to improve screening rates and reduce disparities in
      underscreened communities and population subgroups could further reduce
      colorectal cancer morbidity and mortality. This could be achieved by utilizing
      the full range of screening options and evidence-based interventions for
      increasing screening rates. With additional investments in quality monitoring,
      Americans could be assured that all screening achieves high rates of cancer
      prevention and early detection. To close the gap in screening, this report
      identifies the following priority areas for implementation and research to
      enhance the use and quality of colorectal cancer screening: * Eliminate financial
      barriers to colorectal cancer screening and appropriate follow up. * Widely
      implement interventions that have proven effective at increasing colorectal
      cancer screening, including patient reminder systems and one-on-one interactions
      with providers, educators, or navigators. * Conduct research to assess the
      effectiveness of tailoring programs to match the characteristics and preferences
      of target population groups to increase colorectal cancer screening. * Implement
      systems to ensure appropriate follow-up of positive colorectal cancer screening
      results. * Develop systems to assure high quality of colorectal cancer screening
      programs. * Conduct studies to determine the comparative effectiveness of the
      various colorectal cancer screening methods in usual practice settings.

PMID- 20140036
TI  - [Physical morphology of the root canal taper in the apical region of human
      permanent first molars].
AB  - OBJECTIVE: To investigate the physical morphology of the root canal taper in
      human maxillary and mandibular permanent first molars. METHODS: Forty maxillary
      and 44 mandibular extracted human permanent first molars were investigated. The
      roots were dissected transversely from their apical foramen vertical to the long
      axis of the root, and 1-mm-thick serial sections were made. The root apex side of
      each section was observed with a stereomicroscope at 30 x magnification. The
      maximum and minimum canal diameters were measured at 0, 1, 2, and 3 mm from the
      apical foramen. The physical canal taper in the apical section was calculated.
      RESULTS: 47.5%-60.0% of the narrowest diameter of root canals were present at the
      foramen, and 25.0%-42.5% located at the level of 1 mm from apical foramen. Almost
      all physical configurations of root canals in 3 mm apical region showed a
      bottleneck-like taper. Canal diameters increased rapidly at 1-2 mm with the
      biggest taper, and the taper had a bigger variance (0.07-0.35). The ring of
      shrunken bottleneck was formed at the level of 1 mm from apical foramen. The
      taper of canal in maximal diameter was larger than the one in minimal diameter.
      CONCLUSION: The physical morphology of bottleneck-like taper in apical canal was
      helpful to locate the canal apical stop in root canal treatment.

PMID- 20140037
TI  - [Combination therapy of periodontal intrabony defects with demineralized freeze
      dried bone powder and platelet-rich plasma].
AB  - OBJECTIVE: To evaluate the effect of decalcified freeze-dried bone allograft
      (DFDBA) and DFDBA with platelet-rich plasma (PRP) in the treatment of periodontal
      infrabony defects. METHODS: Fifteen periodontal infrabony defects (30 sites) in
      12 patients with periodontitis (9 patients with chronic periodontitis and 3
      patients with aggressive periodontitis) were selected. Three months after initial
      therapy, they were assigned to either the DFDBA group (10 defects with 20 sites)
      or the DFDBA with PRP group (5 defects with 10 sites). The patients were
      evaluated for plaque index (PI), bleeding index (BI), probing depths (PD) and
      clinical attachment loss (CAL) before the treatment and at 6 months after
      periodontal bone graft surgery. RESULTS: The PI, BI, PD and CAL in the DFDBA
      group were 1.7, 2.7, 6.0 mm and 7.0 mm at baseline; 1.5, 1.8, 3.9 mm and 4.4 mm
      at the 6 months after periodontal surgery. The PD, CAL and BI in DFDBA with PRP
      group at baseline were 6.2 mm, 7.1 mm and 2.9; 3.2 mm, 3.6 mm and 1.7 at the 6
      months after periodontal surgery. The PI did not change significantly after
      surgery in both groups. While both groups showed significant improvement (P<0.01)
      in BI, PD and CAL, the improvement in the DFDBA with PRP group was significant
      greater than in the DFDBA group (P<0.05). CONCLUSION: DFDBA is an effective
      therapy for periodontal intrabony defects. DFDBA with PRP can significantly
      improve the clinical effect of periodontal infrabony defects.

PMID- 20140038
TI  - [FBAT analysis of polymorphisms of vitamin D receptor (Taq I and Fok I) in
      aggressive periodontitis families].
AB  - OBJECTIVE: To analyze the correlation between polymorphisms of the vitamin D
      receptor gene (Taq I and Fok I) and the aggressive periodontitis by FBAT method.
      METHODS: 93 AgP nuclear families including 93 probands and their 155 relatives
      were recruited. The genotype frequency and polymorphism for VDR for the patients
      and their pedigree were detected by using polymerase chain reaction (PCR)
      combined with restriction fragment length polymorphism (RFLP). RESULTS: The
      frequency of allele T and t accounted for 94.6 % and 5.4 % in the total
      populations. No tt genotype were detected. The fathers of probands carried more
      allele t than the mothers(9.8% vs 1.6%, P=0.005). The frequency of allele F and f
      accounted for 57.1 % and 42.9 % in the total populations. The result of family
      based associated test (FBAT) including additive model, dominant model and
      recessive model showed that different alleles of Taq I and Fok I had no
      correlation with the onset of AgP(P>0.05). CONCLUSION: This was the first time to
      detect the VDR gene polymorphisms in Chinese families. The result of FBAT
      analysis can not show the correlation between vitamin D receptor gene
      polymorphisms (Taq I and Fok I) and the onset of AgP.

PMID- 20140039
TI  - [Detection of periodental pathogens in atherosclerotic lesions in patients].
AB  - OBJECTIVE: To detect periodontopathic bacterial DNA in atherosclerotic vascular
      lesions in a group of Chinese patients by using polymerase chain reaction (PCR)
      techniques. METHODS: Ten human specimens of atherosclerotic plaque were obtained
      sterilely. The sclerotic lesions were blade into fine pieces and DNA was isolated
      from the samples. To detect Porphyromonas gingivalis(Pg), Tannerella
      forsythia(Tf), Aggregatibacter actinomycetemcomitans(Aa), Prevotella
      intermedia(Pi), Prevotella nigrescens(Pn), Treponema denticola(Td), Campylobacter
      rectus(Cr), PCR amplification of bacterial 16S ribosomal DNA (rDNA) was carried
      out. RESULTS: PCR assays for bacterial 16S rDNA indicated the presence of
      periodontal pathogens in 3 out of 10 surgical specimens. DNA of Pg were found in
      3 samples, Tf was found only in one among the 3 samples and Pn was found in
      another sample among the 3 samples. CONCLUSION: The data confirm that DNA of
      periodontal pathogens present in atherosclerotic plaques. Pg, Tf, Pn may play a
      role in the development and progression of atherosclerosis in these Chinese
      patients. Further studies with large size samples are needed.

PMID- 20140040
TI  - [Correlation study on polymorphisms of vitamin D receptor gene in patients with
      periodontitis].
AB  - OBJECTIVE: To investigate the relationship between vitamin D receptor (VDR) gene
      polymorphisms and periodontitis. METHODS: Ninety patients with aggressive
      periodontitis(AgP), 34 patients with chronic periodontitis and 91 healthy
      controls were recruited in this study. VDR gene was analyzed by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) with Taq I
      restriction endonuclease. RESULTS: The detection frequency of Tt genotype was
      higher in the aggressive periodontitis patients than in the healthy controls
      (16.7% vs 7.7%, P>0.05). The difference between the female aggressive
      periodontitis patients and healthy controls (20.8% vs 4.2%, P<0.05) was
      statistically significant, but no difference was found between the male patients
      and controls (10.8% vs 11.6%, P>0.05). There was a strong association between
      aggressive periodontitis and Tt genotype in females (AgP patients vs healthy
      controls, OR=6.02). The detection frequency of Taq I ER-alpha genotypes was not
      statistically different between the chronic periodontitis patients and healthy
      controls. CONCLUSION: In female Han Chinese population, the Tt VDR genotype may
      be associated with aggressive periodontitis.

PMID- 20140041
TI  - [Evaluation of the in vitro quantitative measurement of II degree furcation
      involvements in mandibular molars by cone-beam computed tomography].
AB  - OBJECTIVE: To evaluate the accuracy of measurement of II degree furcation
      involvements in molars of dry mandibles by cone-beam computed tomography (CBCT).
      METHODS: Twenty molars with II degree furcation involvements in dry mandibles
      were examined directly and measured by CBCT. Eight parameters were selected to
      describe the exact appearance of each II degree furcation involvements, including
      vertical defect dimensions, horizontal defect dimensions and furcation entrance
      dimensions. The results were compared with the corresponding data obtained by
      probing and periapical radiograph. RESULTS: All furcation involvements could be
      correctly classified by CBCT. For 5 of 8 parameters, no significant difference
      was found between the data obtained by CBCT and probing measurements (P>0.05).
      The distances from furcation entrance to alveolar crest, to bottom of bone
      pocket, and to the deepest site of horizontal bone defect measured by CBCT were
      less than those probed directly (P<0.05), but the differences were less than 0.5
      mm (0.21, 0.24, 0.35 mm, respectively). The localization of furcation entrance
      may cause the differences. Two out of 20 furcation involvements could not be
      detected on periapical radiographs, and only 2 of 8 parameters could be measured
      on periapical radiographs. CONCLUSION: CBCT could provide precise and detailed 3D
      images of II degree furcation involvements in vitro.

PMID- 20140042
TI  - [Fatigue damage analysis of porcelain in all-ceramic crowns].
AB  - OBJECTIVE: To investigate the fatigue damage mechanism of porcelain, and its
      relation with the microscopic defects in clinically failed all-ceramic crowns.
      METHODS: Collecting the bilayered all-ceramic crowns failed in vivo. The
      fractured surfaces and occlusial surfaces of failed crowns were examined by an
      optical microscope followed by detailed fractography investigations using a field
      emission scanning electron microscope. When chemical impurities were of concern,
      energy-dispersive X-ray spectroscopy analysis was performed to examine chemical
      composition. A standard practice for fractography failure analysis of advanced
      ceramics is applied to disclose the fracture mode, and damage character. RESULTS:
      Three types of fracture features are defined as breakdown of the entire crown,
      and porcelain chipping-off/delamination. Alumina crowns were usually
      characterized by breakdown of the entire crown, while zirconia crowns by
      porcelain chipping-off and delamination. The fatigue damage of porcelain was
      classified into surface wear, cone crack, and porcelain delamination. The
      observed microscopic defects in this study included air bubbles and impurity
      particles. CONCLUSION: The multi-point occlusial contacts were recommended in all
      ceramic restorations clinically. The thickness of porcelain is important for the
      anti-fatigue ability of porcelain. Cautions have to be taken to avoid
      contaminations during the veneering processes.

PMID- 20140043
TI  - [Experimental occlusal interference induces the expression of protein gene
      products and substance P in masseter muscles of rats].
AB  - OBJECTIVE: To investigate the peripheral mechanism by studying the histological
      changes of masseter muscles using HE stains and substance P (SP) and protein gene
      product 9.5 (PGP9.5) immunohistochemical stains. METHODS: Fifteen male Sprague
      Dawley were randomly assigned into occlusal interference group (n=12) and control
      group (n=3). In occlusal interference group, 0.4 mm thick crowns were bonded to
      the rats' first molar of the maxillary. In the control group, rats were
      anesthetized and mouths were forced open for about 5 min but restorations were
      not applied. 1, 5, 10, and 21 d after 0.4 mm occlusal alteration treatment,
      mechanical pain thresholds of bilateral masseter muscles were quantitatively
      measured by modified electronic anesthesiometer in control group and occlusal
      interference group. The rats were euthanized by transcardiac perfusion after deep
      anesthetization at different time points. The paraffin sections of masseter
      muscles were made and processed for HE, SP, and PGP9.5 immunohistochemical
      staining. RESULTS: Decreased head withdrawal threshold to mechanical pressure was
      detected in masseter muscles on both sides following occlusal interference.
      Histological stains of masseter muscles presented intact following occlusal
      interference, and no inflammatory cells were observed in both sides. Intensely
      stained PGP9.5 was observed at 1 d in occlusal interference groups and maintained
      until the end of the experiment. SP expression was the most obviously increased
      at 5 d in both sides and gradually decreased to the level of control. CONCLUSION:
      Experimental occlusal interference-induced masticatory muscle pain is associated
      with peripheral sensitization of nociceptive neurons rather than muscle damage
      and inflammation.

PMID- 20140044
TI  - [Relationship of the terminal position of the muscular contraction path and
      centric relation position in different vertical dimension].
AB  - OBJECTIVE: To investigate the relationship of the terminal position of the
      muscular contraction path and centric relation position with different vertical
      dimension. METHODS: The terminal position of the muscular contraction path and
      centric relation position with different vertical dimension were recorded for ten
      edentulous patients with gothic arch. RESULTS: The mesial distance between the
      terminal position of the muscular contraction path and centric relation position
      increased with the vertical dimension. The lateral dimension between the terminal
      position of the muscular contraction path and centric relation position, the
      distribution of the terminal position of the muscular contraction path are not
      correlated to the vertical dimension. The center of the terminal position of the
      muscular contraction path is 1-4 mm ahead of the centric relation position and
      (0.42 + or - 0.47) mm lateral to the centric relation position. The distribution
      of the terminal position of the muscular contraction path is (1.36 + or - 0.58)
      mm in the mesial-distal direction, (1.56 + or - 0.62) mm in the lateral
      direction. CONCLUSION: With the increase of the vertical dimension, the mesial
      distance between the terminal position of the muscular contraction path and
      centric relation position increased.

PMID- 20140045
TI  - [Clinical evaluation of denture made of pure titanium].
AB  - OBJECTIVE: To evaluate the clinical effect of pure titanium used for complete
      denture and removable partial denture. METHODS: Sixty edentulous patients were
      selected. Thirty patients in the test group for pure titanium denture and the
      other 30 in control for Co-Cr Alloy denture. RESULTS: No significant differences
      in clinical effect between dental casting pure titanium and casting Co-Cr alloy
      used for complete denture or removable partial denture. CONCLUSION: Due to the
      properties and biocompatibility, pure titanium can be used for denture base and
      frameworks of removable partial denture.

PMID- 20140046
TI  - [Clinical application of computer-aided design and rapid prototyping technique
      for radioactive seeds contained maxillary device].
AB  - OBJECTIVE: To test a new method to manufacture a maxillary applicator containing
      radioactive seeds for brachytherapy of malignant neoplasms based on computer
      aided design (CAD) and rapid prototyping (RP). METHODS: Six patients with
      maxillary malignancy which had eroded the inferior wall of orbit and skull base
      were included in this study. After excision of the tumors, head CT data of these
      patients were transmitted into the computer. Three-dimensional digital image of
      the patient's defected region was then obtained with special software processing
      based on Mimics 8.11 and Geomagic 7.0 and the resin cast of the defected region
      was manufactured by rapid prototyping. The elastic obturator was then made on
      this resin cast which can duplicate the undercut tissue of the defected region.
      After the obturator was completed, the radiotherapy plan was made. (125)I
      radioactive seeds were implanted into the tissues, and they were also implanted
      into the target area of the obturator which was used as a maxillary applicator at
      the same time. The number of radioactive seeds was then counted and the stability
      of radioactive seeds was determined by CT examination. All these 6 patients were
      followed-up for 12 months. RESULTS: All the obturators had good retention and
      stability and fitted the designed target tissue very well. (125)I radioactive
      seeds in the form of the obturator applicator were stable. For all patients, the
      total number of radioactive seeds used was 189. Among them, 105 seeds, 55.6% of
      the total, were contained in obturator applicators. After the obturator
      applicators were used, the amount of radioactive seeds irradiating the target
      regions was significantly increased when compared with that of before. After
      follow-up of 12 months, there was no recurrence nor severe complications.
      CONCLUSION: (125)I radioactive seeds contained maxillary applicator made by
      computer aided design and rapid prototyping can effectively improve the
      brachytherapy of (125)I when it is used for the post-operation radiotherapy of
      maxillary malignant tumors.

PMID- 20140047
TI  - [Impact of magnetic attachment keepers on magnetic resonance imaging
      examination].
AB  - OBJECTIVE: To evaluate the effects of magnetic attachment keepers on MRI images.
      METHODS: In in vitro part, keepers of MAGFIT EX 400, MAGFIT EX 600 and MAGNEDISC
      800 magnetic attachment systems were cast into standard root-caps with different
      alloy respectively, including nickel-chromium alloy and gold-palladium alloy, or
      not be cast for contrast. In in vivo part, volunteers with keepers in different
      position and amount were included. All the specimens and volunteers were imaged
      by a Siemens SONATA 1.5-T MRI scanner. Extent of the artifacts in every slice was
      measured. The magnitude of the artifacts and the distortion of the anatomic
      structures were compared. RESULTS: All kinds of keepers being studied produced
      obvious MRI artifacts. The extent of MRI artifacts induced by MAGFIT EX 400
      keepers, MAGFIT EX 600 keepers and MAGNEDISC 800 keepers are 158.94 mm, 168.52 mm
      and 173.00 mm, respectively. The images of mental region, tongue, palate, jawbone
      and sinus were evidently obscured by artifacts in all cases. When keeper was put
      in the molar region, the keeper-related MRI artifact may obscure the imaging of
      brain, spinal cord. SE sequence with right-left frequency-encoding direction was
      more desirable in MRI for the patients with magnetic attachment keepers.
      CONCLUSION: Keepers of magnetic attachment system did induce obvious artifacts in
      MRI examination.

PMID- 20140048
TI  - [Effects of different concentrations of glucose infusion during the cleft lip and
      palate repair in infant patients].
AB  - OBJECTIVE: To analyze the feasibility of regular infusion with different
      concentrations of dextrose and blood glucose monitor in infant from 2 to 12
      months during operation. METHODS: Ninety ASA(American Society of
      Anesthesiologists) I-II infants (age 2-12 months) who undertook cleft lip and
      palate repair (excluding patients with congenital diabetes) were divided into
      three groups (30 cases per group). Group I patients were infused with normal
      saline, Group II with 2.5% (mass fraction) dextrose in normal saline and Group
      III with 5% (mass fraction) dextrose, all by a rate of 6-8 mL/ (kg x h). Once the
      patient was sent into the operation room, Electrocardiogram(ECG) and Pulse Oxygen
      Saturation[SpO(2)] monitor were applied regularly; and anesthesia was inducted
      and maintained with sevoflurane in oxygen. The infants' age, gender, weight,
      fasting time, operation time and duration of anesthesia were recorded and the
      blood glucose concentrations before infusion, 10 minutes and 30 minutes after
      induction as well as at the end of operation were recorded. RESULTS: There were
      no differences in age, gender, weight, fasting time, operation time and duration
      of anesthesia among the three groups. The differences of blood glucose
      concentrations before induction had no statistical significance among the three
      groups. The blood glucose concentration after induction was higher than that
      before induction in each group. The occurrence of lower level of blood glucose in
      Group I was 13.3% (4/30, 2.8-4.3 mmol/L), with the lowest value being 3.1 mmol/L.
      None was detected hyperglycemia. In Group II, blood glucose value after induction
      was lower than Group III and higher than Group I at every time point and
      incidence rate of hyperglycemia was 10% (3/30, >11.1 mmol/L), with the highest
      value being 12.7 mmol/L. Blood glucose in Group III was higher than both Group I
      and Group II after infusion. Incidence rate of hyperglycemia in Group III was 70%
      (21/30, >11.1 mmol/L), with the highest value being 22.1 mmol/L. After induciton
      5, 10 min and the end of operation, blood glucose values with group I were (5.8 +
      or - 1.3) mmol/L, (8.4 + or - 1.7) mmol/L and (10.6 + or - 2.8) mmol/L; group II
      were (6.3 + or - 1.4) mmol/L, (8.5 + or - 2.5) mmol/L and (11.3 + or - 2.9)
      mmol/L; group III were (6.6 + or - 1.5) mmol/L, (8.2 + or - 2.1) mmol/L and (12.2
      + or - 3.5) mmol/L. CONCLUSION: 2.5% dextrose (at a rate of 6-8 mL/ (kg x h) is
      appropriate for infants during cleft lip and palate repair, while regular blood
      glucose monitor should be applied during operation.

PMID- 20140049
TI  - [Clinical evaluation of oral midazolam sedation for dental treatment in
      children].
AB  - OBJECTIVE: To assess the safety, effectiveness and acceptability of oral
      midazolam sedation for dental treatment in children. METHODS: Twenty-three health
      children aged 4 to 14 (ASA I), who were classified as 4 or 5 by modified Venham's
      clinic anxiety and cooperative behavior rating scale, referred for dental
      treatment were included in the study. Each child was treated under sedation with
      oral midazolam (0.15-0.70 mg/kg), and totally 45 sedations were conducted. At
      each visit, heart rate, arterial oxygen saturation, respiration rate, sedation
      and behavioral scores were recorded. The level of acceptance and satisfaction of
      the patients and their guardians were recorded after the treatment. RESULTS:
      Among the 23 children, 19 were boys and 4 were girls with mean age of 6.2 years
      old. In all the 45 treatments, the heart rate, respiratory rate and arterial
      oxygen saturation levels were within acceptable clinical limits. Forty planned
      treatments were completed satisfactorily. Oral sedation was ineffective in 3
      children, and they were treated under general anesthesia. Only 2 guardians
      refused to have oral midazolam sedation again. Six of seven children who had
      regular dental check-up could be treated under normal condition. CONCLUSION: Oral
      midazolam (0.15-0.70 mg/kg) could be a safe and acceptable approach of sedation
      for pediatric dental patients.

PMID- 20140050
TI  - [Determinations of the bonding strength with pressure in the same direction for
      two enamel adhesion techniques: self-etching and all-etching].
AB  - OBJECTIVE: To compare the shear strength of the self-etching techniques and the
      all-etching techniques for enamel adhesion and to provide evidence for the
      selection of different bonding methods in clinical practice. METHODS: Ten middle
      incisors recently extracted were collected, each was cut into two parts following
      its sagittal axis, thus divide each tooth into two groups. For group 1 Single
      Bond 2 was used to bond Filtek Z250 resin to the teeth. For group 2, SE Bond was
      used to bond Filtek Z250 resin to the teeth. After that, according to the
      principle of pressing from the incisal margin to the cervix, the shear strength
      of each bonding unit was tested and statistically analyzed. RESULTS: The shear
      strength of Single Bond 2 was significantly higher than that of SE Bond(P<0.01).
      CONCLUSION: All-etching bonding system can provide higher shear strength for
      enamel bonding than that of self-etching bonding system. It is suggested that all
      etching technique should be selected for dental restoration with resin.

PMID- 20140051
TI  - [Histochemical and immunohistochemical double staining for osteolytic related
      factors in keratocystic odontogenic tumor].
AB  - OBJECTIVE: To investigate the activities of bone resorption related cytokines at
      the capsule wall of the keratocystic odontogenic tumor (KCOT) by histochemical
      and immunohistochemical double staining for tartrate-resistant acid phosphatase
      staining (TRAP), receptor activator of nuclear factor-kappaB ligand(RANKL),
      osteoprotegerin(OPG), interleukin1alpha(IL-1alpha)and parathyroid hormone-related
      protein (PTHrP). METHODS: Twenty paraffin blocks of KCOT were sectioned in
      sequence into five slices. One slice was stained with hematoxylin and eosin to
      confirm pathological diagnosis. Each of other four slices was histochemically and
      immunohistochemically double stained separately by TRAP with RANKL, TRAP with
      OPG. TRAP with IL-1alpha and TRAP with PTHrP to observe expressions of these
      factors in KCOT. RESULTS: TRAP positive expression was shown in 10 cases.
      Positive expression of both TRAP and RANKL were detected in 5 cases. RANKL
      positive staining mainly scattered in fibrous connective tissue, blood vessels
      and epithelium was shown in 12 cases. OPG positive staining was detected in 4
      cases. IL-1alpha positive cells were also observed in 10 cases and PTHrP positive
      cells were seen in 6 cases. The TRAP and RANKL positive cells were scattered
      within the connective tissues near the bone. The IL-1alpha positive staining
      cells were observed both in epithelium and connective tissues, but predominately
      in the former. CONCLUSION: The mechanism of osteoclastogenesis of KCOT may also
      be mediated by osteolytic factors such as RANKL, IL-1alpha and PTHrP. These
      factors involved in the activation and differentiation of pre-osteoclasts to form
      osteoclasts, thus finally resulted in jaw bone resorption.

PMID- 20140052
TI  - [Clinical analysis of dental trauma patients in the emergency room].
AB  - OBJECTIVE: To Analyze the etiological and clinical characteristics of dental
      trauma in dental emergency. METHODS: A comprehensive review of 975 emergencies of
      dental trauma seen at the Emergency Room of Peking University School and Hospital
      of Stomatology during a two-year period was performed. General characteristics,
      such as age and gender, time of visit, causes of dental trauma, places where the
      dental trauma happened, diagnoses, and related treatments were analyzed. RESULTS:
      The two age peaks of dental trauma patients under 18 years were 2 to 4 years and
      7 to 12 years. There were more male patients than females in the groups above 7
      year-old, but there were no difference in gender distribution in infants and
      toddlers. Spring had the lowest frequency of dental traumatic emergencies, but
      winter was the busiest season. Dental emergencies with traumatic causes followed
      a pattern during the week. Most patient visits presented during weekends. 24.1%
      of the patients presented to the dental clinic within 2 hours after injury, only
      4.7% of the patients visited the clinic after 24 hours. 64.4% of the children
      younger than 5 years were injured at home, but 82.3% of children aged 5 and older
      and 93.1% adults were injured in the outdoor environment. The number of injured
      teeth in left and right side had no significant difference (P>0.05). Maxillary
      incisors were easily to be affected, especially the maxillary central incisor.
      Crown fracture was the most common traumatic type. The combination of dental
      trauma and oral and maxillofacial soft tissue injury was experienced by 692
      patients (71.0%). CONCLUSION: Dental trauma was one of the common diseases in
      oral emergencies. Knowledge of the etiological and clinical characteristics of
      emergency dental trauma could help us to treat them and make specific preventive
      measures. Clinical examination should be comprehensive and meticulous to avoid
      misdiagnosis, for emergency dental trauma often involving multiple teeth, and
      associated with different degrees of maxillofacial soft tissue injury.

PMID- 20140053
TI  - [Clinical effects of ridge augmentation with the half-columnar shaped mandibular
      bone block for the placement of dental implants].
AB  - OBJECTIVE: To evaluate the treatment effects of the half-columnar shaped
      mandibular block bone onlay grafting technique for augmentation of the resorbed
      maxillary anterior alveolar ridge after single tooth missing. METHODS: A total of
      15 sites of 14 patients received ridge augmentation surgeries. The recipient
      sites were prepared with trephines, the half-columnar shaped bone blocks were
      harvested from the ramus and external oblique ridges with trephines according to
      diameters of the recipient sites. The bone blocks were placed as lateral onlay
      grafts on recipient beds and secured by means of titanium screws. Particulate
      bone was added and absorbable membranes were used to stabilize and protect the
      grafts. After a mean interval of 4.5 months of healing the flaps were re-opened,
      the screws were removed and non-submerged implants were placed. The width and
      height of the alveolar ridges were recorded. After 3 months, implant-supported
      crowns were provided to the patients. One year later, the peri-impant condition
      and the marginal bone resorption on the proximal sites were observed. RESULTS:
      Mean lateral augmentation obtained at the time of bone grafting was (3.8 + or -
      0.8) mm, 5 out of 15 sites exhibited a mean of 3 mm of vertical augmentation. The
      mean healing time was 4.5 months, the mean percentage of horizontal and vertical
      bone resorption in the mean time were 8% and 7% respectively. No major
      complications were recorded at donor sites. No implant was lost during the study
      period. Clinical parameters and probing depth (< or = 4 mm) demonstrated the
      presence of a healthy peri-implant mucosa after 1 year of prosthetic
      reconstruction. The clinical and radiographic bone observations showed no more
      than 1.2 mm of resorption after bone graft and implant placement. CONCLUSION: The
      half-columnar shaped mandibular bone graft (from the ramus and external oblique
      ridge) is a promising technique for bone augmentation in localized alveolar ridge
      defects after single tooth missing. This procedure offers easy access, good bone
      quantity for localized repair, low morbidity, decreased complaints of
      postoperative sensory disturbances or discomfort, minimal graft resorption, and a
      shorter healing time as compared with other methods for bone repair.

PMID- 20140054
TI  - [Validity of tooth volume determinations using cone beam computed tomography].
AB  - OBJECTIVE: To determine the accuracy of volumetric analysis of teeth in vivo
      using cone beam computed tomography (CBCT). METHODS: The physical volume (Vw) of
      24 bicuspids extracted for orthodontic purposes (16 were imaged with the i-CAT
      and 8 with the CB MercuRay before extraction) was determined using water
      displacement technique. Corresponding pre-treatment CBCT image data were uploaded
      into Amira 4.0 for segmentation and radiographic volume (Va). All measurements
      were performed twice by two observers. The statistical difference between Vw and
      Va was assessed using a paired t-test. The intra- and inter-observer reliability
      was determined by calculating Pearson correlation coefficients and intraclass
      correlation coefficients (ICC). RESULTS: The overall mean Vw of teeth specimens
      was (0.553 + or - 0.082) cm(3), while the mean Va was (0.548 + or - 0.079) cm(3),
      (0.529 + or - 0.078) cm(3) for observer 1, and (0.567 + or - 0.085) cm(3) for
      observer 2. There were statistically significant differences between Va and Vw
      (P<0.05). Between two observers, Va had statistically significant difference
      (P<0.05). The inter- and intra-observers correlation coefficient for Vw was high.
      Lastly, surface smoothing reduced the volume by 3%-12%. CONCLUSION: In vivo
      determination of tooth volumes from CBCT data is feasible. The measurements
      slightly deviate from the physical volumes within -4% to 7%. Smoothing operations
      reduce volume measurements.

PMID- 20140055
TI  - [Clinical study of the application of non-invasive porcelain veneer to improve
      the aesthetic effects in maxillary anterior area].
AB  - OBJECTIVE: To evaluate the clinical results of application of non-invasive
      porcelain veneer to reduce the black triangle of implant and adjacent teeth and
      to improve the aesthetic effect in the maxillary anterior area. METHODS: The
      study included 10 patients (Male: 4, Female: 6; average age: 41.5) accessioned
      during May 2007 to August 2009 in Peking University School of Stomatology. The
      provisional restorations were delivery on implant after 3-6 months healing period
      of the implant. The non-invasive porcelain veneers were used in the round tip
      adjacent teeth with gingival recession in the indicated patients. Main measured
      parameters on the model included horizontal distance and vertical distance. The
      Horizontal distance refers to the black triangle bottom which is from adjacent
      surface of the natural teeth to the implant restoration at the gingival level.
      The vertical distance is from mid-point of the triangle bottom to the contact
      point. Clinical observed items included bleeding index (BI), integrity of
      porcelain veneer and degree of satisfaction of the patients. RESULTS: A total of
      14 adjacent natural teeth in 10 patients were cemented with porcelain veneer. No
      porcelain veneer was lost or fracture during follow-up period (range 6 to 27
      months, mean of 10.4 months). Mean bleeding index 0-1. The horizontal distance
      was reduced from (3.1 + or - 0.8) mm before restoration to (1.1 + or - 0.5) mm
      after restoration. Vertical distance from (5.3 + or - 1.1) mm to (2.9 + or - 0.7)
      mm. All patients were satisfied with the clinical result. CONCLUSION: The data
      and the experience described in this study indicate that improvement of aesthetic
      effects by using no-invasive porcelain veneer techniques can be a predictable
      technique for patients with periodontal disease. Further study is needed to
      determine the long-term result of the technique.

PMID- 20140056
TI  - [Methodology of computer-aided design of automatic artificial tooth selection for
      complete denture].
AB  - OBJECTIVE: To study the method of automatic tooth selection for computer-aided
      design in complete denture, evaluate the results by comparison with traditional
      denture tooth selection. METHODS: 3D data of occlusal rim made by the dentist
      were obtained with a 3D laser scanner and specific points on the occlusal rim
      were measured on Imageware11 platform. Based on Matlab 7.1 software platform, an
      automatic tooth selection software was programmed with adequate consideration of
      complete denture tooth selection factors, for example: face form of the patient,
      mesiodistal diameter of the artificial anterior teeth and posterior teeth, etc.
      Oclusal rim and edentulous models were selected from 20 patients. The artifical
      teeth were selected by both technician and software. The result of automatic
      tooth selection was evaluated by comparison with traditional method. RESULTS: In
      20 cases the concordant rate of automatic and traditional method is 70%.
      CONCLUSION: The method of automatic tooth selection for computer-aided design in
      complete denture was realized in accordance with traditional method of denture
      tooth selection, the relationship between the curve of artificial teeth arranged
      on the occlusal rim and cuspid line--which was calculated accurately; automatic
      denture tooth selection; the denture tooth selected by software can be directly
      used in CAD complete denture tooth arrangement.

PMID- 20140057
TI  - [Computer-aided design for occlusal rest of the removable partial denture].
AB  - OBJECTIVE: To explore the route of automatic computer-aided design for occlusal
      rest of the removable partial denture. METHODS: A new module for the design of
      occlusal rest was developed. The three-dimensional data of a partially dentate
      dental cast was obtained and imported into the new module. The contour of the
      occlusal's tissue surface was identified. Then, the tissue surface and polished
      surface were constructed respectively and connected to each other to form an
      integrated entity. RESULTS: The surface of the occlusal rest was smooth and the
      curvature matched that of the surrounding area of the abutment tooth. The
      accuracy was satisfying. CONCLUSION: Design of occlusal rest was much more
      convenient and time-saving using the newly developed module. The future
      development of special software package for the design of removable partial
      denture will benefit from it.

PMID- 20140058
TI  - [Post-operation nursing for patients with autologous transplantation of the
      microvascular submandibular gland].
AB  - OBJECTIVE: To summarize the complications' prevention and nursing experience for
      patients after autologous transplantation of the microvascular submandibular
      gland for severe keratoconjunctivis sicca. METHODS: Retrospective analysis of 141
      patients(151 sides) after autologous microvascular submandibular gland transfer
      operation was undertaken to record the timing and incidence of major
      complications and to summarize the nursing experience. RESULTS: The main
      complications after the transplantation were: vascular crisis, catheter
      obstruction, salivary fistula and temporary paralysis of hypoglossal nerve.
      Related nursing measures in response to these complications were discussed.
      CONCLUSION: Targeted nursing interventions for patients with autologous
      transplantation the submandibular gland have a positive effect on the prevention
      of the surgical complications.

PMID- 20140059
TI  - [Progress on study on oral lesions in patients with AIDS].
AB  - A large number of studies showed that hairy leukoplakia, pseudomembranous
      candidiasis, Kaposi' sarcoma, non-Hodgkin's lymphoma, linear gingival erythema,
      necrotizing ulcerative periodontitis and necrotizing ulcerative gingivitis were
      the most common lesions in patients with HIV infection and AIDS, and their higher
      prevalence and incidence rates correlated with the falling CD4 counts and higher
      virus load of the patients. The use of highly active antiretroviral therapy
      (HAART) was associated with decreases in the prevalence of oral diseases. Oral
      manifestations may represent early signs of AIDS disease and call attention to
      disease progression. Oral fluid has been shown to possess superior sensitivity
      for HIV antibody detection as serum.

PMID- 20140060
TI  - Oxonium Ion Mediated Synthesis of 4-Substituted Spiro-Isoxazolines.
AB  - The stereoselective synthesis of 4-bromo-spiro-isoxazolines was achieved in one
      step through the bromination of various isoxazoles that contain a pendant alcohol
      or carboxylic acid functional group. Isoxazole bromination leads to a bromonium
      ion intermediate which opens either by neighboring oxygen lone pair electrons or
      by intramolecular nucleophilic attack. Single X-ray crystal data provides
      evidence that the two contiguous stereocenters of the spiro-isoxazoline are
      formed by the anti intramolecular attack of the nucleophile relative to bromine
      since there is an anti stereochemical relationship between the spirocyclic ring
      oxygen and the bromine atom.

PMID- 20140061
TI  - Bright, Red Single-Molecule Emitters: Synthesis and Properties of Environmentally
      Sensitive Dicyanomethylenedihydrofuran (DCDHF) Fluorophores with Bisaromatic
      Conjugation.
AB  - A group of new fluorescent dye materials for single-molecule imaging applications
      comprised of an amine donor, a pi-system comprised of phenyl and thiophene rings
      and a 2-dicyanomethylene-3-cyano-2,5-dihydrofuran acceptor group have been
      synthesized. Relative to comparable single-ring compounds these doubly aromatic
      conjugated fluorophores have red-shifted absorption and emission usually
      accompanied by significantly increased quantum yields. Solvatochromism studies
      indicate that the photophysical properties of these dyes are sensitive to the
      solvent polarity and environmental rigidity. Photophysical studies demonstrate
      that these DCDHF dye materials are strong single-molecule emitters and the total
      number of detected photons per molecule is among the highest thus far for this
      family of fluorophores.

PMID- 20140063
TI  - Sequence Analysis of the Full-length cDNA and Protein Structure Homology Modeling
      of FABP2 from Paralichthys Olivaceus.
AB  - Using zebrafish intestinal fatty acid-binding protein 2 (FABP2) mRNA sequence as
      the initial query probe, four highly homologous Paralichthys olivaceus EST
      sequences were retrieved from Genbank database. The assembled full-length cDNA
      contains the open reading frame of P. olivaceus FABP2 gene, which was validated
      by subsequent RT-PCR cloning. In the coding region, the average GC content is
      56%, but it would reach 76.8% if only counting for the third base of the codons.
      The deduced P. olivaceus FABP2 polypeptide contains 132 amino acids (aa), with a
      predicted molecular size of 15.3 kD and pI at 6.74. This protein multiple
      alignment has shown that this peptide is 75.7% identical to the corresponding
      homologous protein in Danio rerio. Among the 7 aa that are essential for FABP2
      function, 3 were found to be conserved among P. olivaceus, Danio rerio, Tetraodon
      nigroviridi, Rattus norvegicus, and Homo sapiens. The study provides essential
      information on molecular evolution and function of FABP family.

PMID- 20140062
TI  - Classifying coding DNA with nucleotide statistics.
AB  - In this report, we compared the success rate of classification of coding
      sequences (CDS) vs. introns by Codon Structure Factor (CSF) and by a method that
      we called Universal Feature Method (UFM). UFM is based on the scoring of purine
      bias (Rrr) and stop codon frequency. We show that the success rate of CDS/intron
      classification by UFM is higher than by CSF. UFM classifies ORFs as coding or non
      coding through a score based on (i) the stop codon distribution, (ii) the product
      of purine probabilities in the three positions of nucleotide triplets, (iii) the
      product of Cytosine (C), Guanine (G), and Adenine (A) probabilities in the 1st,
      2nd, and 3rd positions of triplets, respectively, (iv) the probabilities of G in
      1st and 2nd position of triplets and (v) the distance of their GC3 vs. GC2 levels
      to the regression line of the universal correlation. More than 80% of CDSs (true
      positives) of Homo sapiens (>250 bp), Drosophila melanogaster (>250 bp) and
      Arabidopsis thaliana (>200 bp) are successfully classified with a false positive
      rate lower or equal to 5%. The method releases coding sequences in their coding
      strand and coding frame, which allows their automatic translation into protein
      sequences with 95% confidence. The method is a natural consequence of the
      compositional bias of nucleotides in coding sequences.

PMID- 20140064
TI  - A Rough Set-Based Model of HIV-1 Reverse Transcriptase Resistome.
AB  - Reverse transcriptase (RT) is a viral enzyme crucial for HIV-1 replication.
      Currently, 12 drugs are targeted against the RT. The low fidelity of the RT
      mediated transcription leads to the quick accumulation of drug-resistance
      mutations. The sequence-resistance relationship remains only partially
      understood. Using publicly available data collected from over 15 years of HIV
      proteome research, we have created a general and predictive rule-based model of
      HIV-1 resistance to eight RT inhibitors. Our rough set-based model considers
      changes in the physicochemical properties of a mutated sequence as compared to
      the wild-type strain. Thanks to the application of the Monte Carlo feature
      selection method, the model takes into account only the properties that
      significantly contribute to the resistance phenomenon. The obtained results show
      that drug-resistance is determined in more complex way than believed. We
      confirmed the importance of many resistance-associated sites, found some sites to
      be less relevant than formerly postulated and-more importantly-identified several
      previously neglected sites as potentially relevant. By mapping some of the newly
      discovered sites on the 3D structure of the RT, we were able to suggest possible
      molecular-mechanisms of drug-resistance. Importantly, our model has the ability
      to generalize predictions to the previously unseen cases. The study is an example
      of how computational biology methods can increase our understanding of the HIV-1
      resistome.

PMID- 20140065
TI  - Gene expression based leukemia sub-classification using committee neural
      networks.
AB  - Analysis of gene expression data provides an objective and efficient technique
      for sub-classification of leukemia. The purpose of the present study was to
      design a committee neural networks based classification systems to subcategorize
      leukemia gene expression data. In the study, a binary classification system was
      considered to differentiate acute lymphoblastic leukemia from acute myeloid
      leukemia. A ternary classification system which classifies leukemia expression
      data into three subclasses including B-cell acute lymphoblastic leukemia, T-cell
      acute lymphoblastic leukemia and acute myeloid leukemia was also developed. In
      each classification system gene expression profiles of leukemia patients were
      first subjected to a sequence of simple preprocessing steps. This resulted in
      filtering out approximately 95 percent of the non-informative genes. The
      remaining 5 percent of the informative genes were used to train a set of
      artificial neural networks with different parameters and architectures. The
      networks that gave the best results during initial testing were recruited into a
      committee. The committee decision was by majority voting. The committee neural
      network system was later evaluated using data not used in training. The binary
      classification system classified microarray gene expression profiles into two
      categories with 100 percent accuracy and the ternary system correctly predicted
      the three subclasses of leukemia in over 97 percent of the cases.

PMID- 20140066
TI  - An Efficient Method to Identify Conditionally Activated Transcription Factors and
      their Corresponding Signal Transduction Pathway Segments.
AB  - A signal transduction pathway (STP) is a cascade composed of a series of signal
      transferring steps, which often activate one or more transcription factors (TFs)
      to control the transcription of target genes. Understanding signaling pathways is
      important to our understanding of the molecular mechanisms of disease. Many
      condition-annotated pathways have been deposited in public databases. However,
      condition-annotated pathways are far from complete, considering the large number
      of possible conditions. Computational methods to assist in the identification of
      conditionally activated pathways are greatly needed. In this paper, we propose an
      efficient method to identify conditionally activated pathway segments starting
      from the identification of conditionally activated TFs, by incorporating protein
      DNA binding data, gene expression data and protein interaction data. Applying our
      methods on several microarray datasets, we have discovered many significantly
      activated TFs and their corresponding pathway segments, which are supported by
      evidence in the literature. AVAILABILITY:
      http://www.cs.ucf.edu/~haihu/Download/BBI/ACTPATH.htm.

PMID- 20140067
TI  - Using the Multiple Analysis Approach to Reconstruct Phylogenetic Relationships
      among Planktonic Foraminifera from Highly Divergent and Length-polymorphic SSU
      rDNA Sequences.
AB  - The high sequence divergence within the small subunit ribosomal RNA gene (SSU
      rDNA) of foraminifera makes it difficult to establish the homology of individual
      nucleotides across taxa. Alignment-based approaches so far relied on time
      consuming manual alignments and discarded up to 50% of the sequenced nucleotides
      prior to phylogenetic inference. Here, we investigate the potential of the
      multiple analysis approach to infer a molecular phylogeny of all modern
      planktonic foraminiferal taxa by using a matrix of 146 new and 153 previously
      published SSU rDNA sequences. Our multiple analysis approach is based on eleven
      different automated alignments, analysed separately under the maximum likelihood
      criterion. The high degree of congruence between the phylogenies derived from our
      novel approach, traditional manually homologized culled alignments and the fossil
      record indicates that poorly resolved nucleotide homology does not represent the
      most significant obstacle when exploring the phylogenetic structure of the SSU
      rDNA in planktonic foraminifera. We show that approaches designed to extract
      phylogenetically valuable signals from complete sequences show more promise to
      resolve the backbone of the planktonic foraminifer tree than attempts to
      establish strictly homologous base calls in a manual alignment.

PMID- 20140068
TI  - affyPara-a Bioconductor Package for Parallelized Preprocessing Algorithms of
      Affymetrix Microarray Data.
AB  - Microarray data repositories as well as large clinical applications of gene
      expression allow to analyse several hundreds of microarrays at one time. The
      preprocessing of large amounts of microarrays is still a challenge. The
      algorithms are limited by the available computer hardware. For example, building
      classification or prognostic rules from large microarray sets will be very time
      consuming. Here, preprocessing has to be a part of the cross-validation and
      resampling strategy which is necessary to estimate the rule's prediction quality
      honestly.This paper proposes the new Bioconductor package affyPara for
      parallelized preprocessing of Affymetrix microarray data. Partition of data can
      be applied on arrays and parallelization of algorithms is a straightforward
      consequence. The partition of data and distribution to several nodes solves the
      main memory problems and accelerates preprocessing by up to the factor 20 for 200
      or more arrays.affyPara is a free and open source package, under GPL license,
      available form the Bioconductor project at www.bioconductor.org. A user guide and
      examples are provided with the package.

PMID- 20140069
TI  - Universal Features for the Classification of Coding and Non-coding DNA Sequences.
AB  - In this report, we revisited simple features that allow the classification of
      coding sequences (CDS) from non-coding DNA. The spectrum of codon usage of our
      sequence sample is large and suggests that these features are universal. The
      features that we investigated combine (i) the stop codon distribution, (ii) the
      product of purine probabilities in the three positions of nucleotide triplets,
      (iii) the product of Cytosine, Guanine, Adenine probabilities in 1st, 2nd, 3rd
      position of triplets, respectively, (iv) the product of G and C probabilities in
      1st and 2nd position of triplets. These features are a natural consequence of the
      physico-chemical properties of proteins and their combination is successful in
      classifying CDS and non-coding DNA (introns) with a success rate >95% above 350
      bp. The coding strand and coding frame are implicitly deduced when the sequences
      are classified as coding.

PMID- 20140070
TI  - Graphical user interfaces for molecular dynamics-quo vadis?
AB  - In the past years an increasing number of graphical user interfaces for Molecular
      Dynamics (MD) were presented and concomitantly, more and more Molecular Dynamics
      studies were published. With the easier application of MD software packages the
      field runs the risk however, of being pervaded with unreliable results.
      Therefore, possible benefits and caveats have to be carefully balanced. Here we
      outline in which respects a broader access of MD via graphical user interfaces
      may help to increase the usability of Molecular Dynamics simulations while
      maintaining their quality.

PMID- 20140071
TI  - Bioinformatics as a tool for assessing the quality of sub-cellular proteomic
      strategies and inferring functions of proteins: plant cell wall proteomics as a
      test case.
AB  - Bioinformatics is used at three different steps of proteomic studies of sub
      cellular compartments. First one is protein identification from mass spectrometry
      data. Second one is prediction of sub-cellular localization, and third one is the
      search of functional domains to predict the function of identified proteins in
      order to answer biological questions. The aim of the work was to get a new tool
      for improving the quality of proteomics of sub-cellular compartments. Starting
      from the analysis of problems found in databases, we designed a new Arabidopsis
      database named ProtAnnDB (http://www.polebio.scsv.ups-tlse.fr/ProtAnnDB/). It
      collects in one page predictions of sub-cellular localization and of functional
      domains made by available software. Using this database allows not only
      improvement of interpretation of proteomic data (top-down analysis), but also of
      procedures to isolate sub-cellular compartments (bottom-up quality control).

PMID- 20140072
TI  - Predicting consensus structures for RNA alignments via pseudo-energy
      minimization.
AB  - Thermodynamic processes with free energy parameters are often used in algorithms
      that solve the free energy minimization problem to predict secondary structures
      of single RNA sequences. While results from these algorithms are promising, an
      observation is that single sequence-based methods have moderate accuracy and more
      information is needed to improve on RNA secondary structure prediction, such as
      covariance scores obtained from multiple sequence alignments. We present in this
      paper a new approach to predicting the consensus secondary structure of a set of
      aligned RNA sequences via pseudo-energy minimization. Our tool, called RSpredict,
      takes into account sequence covariation and employs effective heuristics for
      accuracy improvement. RSpredict accepts, as input data, a multiple sequence
      alignment in FASTA or ClustalW format and outputs the consensus secondary
      structure of the input sequences in both the Vienna style Dot Bracket format and
      the Connectivity Table format. Our method was compared with some widely used
      tools including KNetFold, Pfold and RNAalifold. A comprehensive test on different
      datasets including Rfam sequence alignments and a multiple sequence alignment
      obtained from our study on the Drosophila X chromosome reveals that RSpredict is
      competitive with the existing tools on the tested datasets. RSpredict is freely
      available online as a web server and also as a jar file for download at
      http://datalab.njit.edu/biology/RSpredict.

PMID- 20140073
TI  - Automated detection of conformational epitopes using phage display Peptide
      sequences.
AB  - BACKGROUND: Precise determination of conformational epitopes of neutralizing
      antibodies represents a key step in the rational design of novel vaccines. A
      powerful experimental method to gain insights on the physical chemical nature of
      conformational epitopes is the selection of linear peptides that bind with high
      affinities to a monoclonal antibody of interest by phage display technology.
      However, the structural characterization of conformational epitopes from these
      mimotopes is not straightforward, and in the past the interpretation of peptide
      sequences from phage display experiments focused on linear sequence analysis to
      find a consensus sequence or common sequence motifs. RESULTS: We present a fully
      automated search method, EpiSearch that predicts the possible location of
      conformational epitopes on the surface of an antigen. The algorithm uses peptide
      sequences from phage display experiments as input, and ranks all surface exposed
      patches according to the frequency distribution of similar residues in the
      peptides and in the patch. We have tested the performance of the EpiSearch
      algorithm for six experimental data sets of phage display experiments, the human
      epidermal growth factor receptor-2 (HER-2/neu), the antibody mAb Bo2C11 targeting
      the C(2) domain of FVIII, antibodies mAb 17b and mAb b12 of the HIV envelope
      protein gp120, mAb 13b5 targeting HIV-1 capsid protein and 80R of the SARS
      coronavirus spike protein. In all these examples the conformational epitopes as
      determined by the X-ray crystal structures of the antibody-antigen complexes,
      were found within the highest scoring patches of EpiSearch, covering in most
      cases more than 50% residues of experimental observed conformational epitopes.
      Input options of the program include mapping of a single peptide or a set of
      peptides on the antigen structure, and the results of the calculation can be
      visualized on our interactive web server. AVAILABILITY: Users can access the
      EpiSearch from our web server http://curie.utmb.edu/episearch.html.

PMID- 20140074
TI  - Gromita: a fully integrated graphical user interface to gromacs 4.
AB  - Gromita is a fully integrated and efficient graphical user interface (GUI) to the
      recently updated molecular dynamics suite Gromacs, version 4. Gromita is a cross
      platform, perl/tcl-tk based, interactive front end designed to break the command
      line barrier and introduce a new user-friendly environment to run molecular
      dynamics simulations through Gromacs. Our GUI features a novel workflow interface
      that guides the user through each logical step of the molecular dynamics setup
      process, making it accessible to both advanced and novice users. This tool
      provides a seamless interface to the Gromacs package, while providing enhanced
      functionality by speeding up and simplifying the task of setting up molecular
      dynamics simulations of biological systems. Gromita can be freely downloaded from
      http://bio.demokritos.gr/gromita/.

PMID- 20140075
TI  - Inferring Transcriptional Interactions by the Optimal Integration of ChIP-chip
      and Knock-out Data.
AB  - How to combine heterogeneous data sources for reliable prediction of
      transcriptional regulation is a challenge. Here we present an easy but powerful
      method to integrate Chromatin immunoprecipitation (ChIP)-chip and knock-out data.
      Since these two types of data provide complementary (physical and functional)
      information about transcription, the method combining them is expected to achieve
      high detection rates and very low false positive rates. We try to seek the
      optimal integration of these two data using hyper-geometric distribution. We
      evaluate our method on yeast data and compare our predictions with YEASTRACT,
      high-quality ChIP-chip data, and literature. The results show that even using low
      quality ChIP-chip data, our method uncovers more relations than those inferred
      before from high-quality data. Furthermore our method achieves a low false
      positive rate. We find experimental and computational evidence in literature for
      most transcription factor (TF)-gene relations uncovered by our method.

PMID- 20140076
TI  - New sensitive kinetic spectrophotometric methods for determination of omeprazole
      in dosage forms.
AB  - New rapid, sensitive, and accurate kinetic spectrophotometric methods were
      developed, for the first time, to determine omeprazole (OMZ) in its dosage forms.
      The methods were based on the formation of charge-transfer complexes with both
      iodine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The variables that
      affected the reactions were carefully studied and optimized. The formed complexes
      and the site of interaction were examined by UV/VIS, IR, and (1)H-NMR techniques,
      and computational molecular modeling. Under optimum conditions, the stoichiometry
      of the reactions between OMZ and the acceptors was found to be 1 : 1. The order
      of the reactions and the specific rate constants were determined. The
      thermodynamics of the complexes were computed and the mechanism of the reactions
      was postulated. The initial rate and fixed time methods were utilized for the
      determination of OMZ concentrations. The linear ranges for the proposed methods
      were 0.10-3.00 and 0.50-25.00 mug mL(-1) with the lowest LOD of 0.03 and 0.14 mug
      mL(-1) for iodine and DDQ, respectively. Analytical performance of the methods
      was statistically validated; RSD was <1.25% for the precision and <1.95% for the
      accuracy. The proposed methods were successfully applied to the analysis of OMZ
      in its dosage forms; the recovery was 98.91-100.32% +/- 0.94-1.84, and was found
      to be comparable with that of reference method.

PMID- 20140077
TI  - Evaluation of Fructooligosaccharides and Inulins as Potentially Health Benefiting
      Food Ingredients by HPAEC-PED and MALDI-TOF MS.
AB  - This paper describes the complementarity of high-performance anion exchange
      chromatography coupled with pulsed electrochemical detection (HPAEC-PED) and
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF-MS) to
      evaluate commercial available fructans (fructooligosaccharides (FOS) and
      inulins), having different degrees of polymerization (DP) which are usually
      employed by food industry as functional ingredients either for their prebiotic
      properties or as a fat replacer, giving a fat-like mouth feel and texture. The
      developed HPAEC-PED methods are able to analyze FOS (fructans with DP 3-10) and
      inulins (DP ranging from 3 to 80) with a good resolution and relatively short
      retention times to evaluate structural differences between fructooligosaccharide
      and inulins and the possible presence of inulooligosaccharides as well as of
      branching. To characterize FOS and inulin at different degrees of polymerization
      and to assure correct molecular assignment, MALDI-TOF MS analysis was also
      investigated. The 2,5-dihydroxy benzoic acid (2,5-DHB) was found to be the best
      matrix for FOS analysis as Actilight and Raftilose P95 products, while 3
      aminoquinoline (3-AQ) seems to be the best matrix for inulin with higher DP. The
      applicability of the optimized methods to the identification and determination of
      FOS contained in a symbiotic milk as well as a type of inulin added as functional
      ingredient to a cooked ham is demonstrated.

PMID- 20140078
TI  - Kinetic spectrophotometric determination of certain cephalosporins in
      pharmaceutical formulations.
AB  - A simple, reliable, and sensitive kinetic spectrophotometric method was developed
      for determination of eight cephalosporin antibiotics, namely, Cefotaxime sodium,
      Cephapirin sodium, Cephradine dihydrate, Cephalexin monohydrate, Ceftazidime
      pentahydrate, Cefazoline sodium, Ceftriaxone sodium, and Cefuroxime sodium. The
      method depends on oxidation of each of studied drugs with alkaline potassium
      permanganate. The reaction is followed spectrophotometrically by measuring the
      rate of change of absorbance at 610 nm. The initial rate and fixed time (at 3
      minutes) methods are utilized for construction of calibration graphs to determine
      the concentration of the studied drugs. The calibration graphs are linear in the
      concentration ranges 5-15 mug mL(-1) and 5-25 mug mL(-1) using the initial rate
      and fixed time methods, respectively. The results are validated statistically and
      checked through recovery studies. The method has been successfully applied for
      the determination of the studied cephalosporins in commercial dosage forms.
      Statistical comparisons of the results with the reference methods show the
      excellent agreement and indicate no significant difference in accuracy and
      precision.

PMID- 20140079
TI  - A Multidisciplinary Investigation to Determine the Structure and Source of
      Dimeric Impurities in AMG 517 Drug Substance.
AB  - In the initial scale-up batches of the experimental drug substance AMG 517, a
      pair of unexpected impurities was observed by HPLC. Analysis of data from initial
      LC-MS experiments indicated the presence of two dimer-like molecules. One
      impurity had an additional sulfur atom incorporated into its structure relative
      to the other impurity. Isolation of the impurities was performed, and further
      structural elucidation experiments were conducted with high-resolution LC-MS and
      2D NMR. The dimeric structures were confirmed, with one of the impurities having
      an unexpected C-S-C linkage. Based on the synthetic route of AMG 517, it was
      unlikely that these impurities were generated during the last two steps of the
      process. Stress studies on the enriched impurities were carried out to further
      confirm the existence of the C-S-C linkage in the benzothiazole portion of AMG
      517. Further investigation revealed that these two dimeric impurities originated
      from existing impurities in the AMG 517 starting material, N-acetyl
      benzothiazole. The characterization of these two dimeric impurities allowed for
      better quality control of new batches of the N-acetyl benzothiazole starting
      material. As a result, subsequent batches of AMG 517 contained no reportable
      levels of these two impurities.

PMID- 20140080
TI  - Selective Spectrophotometric and Spectrofluorometric Methods for the
      Determination of Amantadine Hydrochloride in Capsules and Plasma via
      Derivatization with 1,2-Naphthoquinone-4-sulphonate.
AB  - New selective and sensitive spectrophotometric and spectrofluorometric methods
      have been developed and validated for the determination of amantadine
      hydrochloride (AMD) in capsules and plasma. The methods were based on the
      condensation of AMD with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline
      medium to form an orange-colored product. The spectrophotometric method involved
      the measurement of the colored product at 460 nm. The spectrofluorometric method
      involved the reduction of the product with potassium borohydride, and the
      subsequent measurement of the formed fluorescent reduced AMD-NQS product at 382
      nm after excitation at 293 nm. The variables that affected the reaction were
      carefully studied and optimized. Under the optimum conditions, linear
      relationships with good correlation coefficients (0.9972-0.9974) and low LOD
      (1.39 and 0.013 mug mL(-1)) were obtained in the ranges of 5-80 and 0.05-10 mug
      mL(-1) for the spectrophotometric and spectrofluorometric methods, respectively.
      The precisions of the methods were satisfactory; RSD </=2.04%. Both methods were
      successfully applied to the determination of AMD in capsules. As its higher
      sensitivity, the spectrofluorometric method was applied to the determination of
      AMD in plasma; the recovery was 96.3-101.2 +/- 0.57-4.2%. The results obtained by
      the proposed methods were comparable with those obtained by the official method.

PMID- 20140081
TI  - Preparation, characterization, and analytical application of ramipril membrane
      based ion-selective electrode.
AB  - The fabrication and electrochemical evaluation of two PVC membrane-based Ion
      Selective electrodes responsive for ramipril drug have been proposed. The
      sensitive membranes were prepared using ramipril-phosphomolibdate and ramipril
      tetraphenylborate ion-pair complexes as electroactive sensing materials in
      plasticized PVC support. The electrodes based on these materials provide near
      Nernestian response (sensitivity of 53 +/- 0.5-54 +/- 0.5 mV/concentration
      decade) covering the concentration range of 1.0 x 10(-2)-1.0 x 10(-5) mol L(-1)
      with a detection limit of 3.0 x 10(-6)-4.0 x 10(-6) mol L(-1). The suggested
      electrodes have been successfully used in the determination of ramipril drug in
      some pharmaceutical formulations using direct potentiometry with average recovery
      of >96% and mean standard deviation of <3% (n = 5).

PMID- 20140082
TI  - Synthesis and Characterization of Organic-Inorganic Nanocomposite Poly-o
      anisidine Sn(IV) Arsenophosphate: Its Analytical Applications as Pb(II) Ion
      Selective Membrane Electrode.
AB  - Poly-o-anisidine Sn(IV) arsenophosphate is a newly synthesized nanocomposite
      material and has been characterized on the basis of its chemical composition, ion
      exchange capacity, TGA-DTA, FTIR, X-RAY, SEM, and TEM studies. On the basis of
      distribution studies, the exchanger was found to be highly selective for lead
      that is an environmental pollutant. For the detection of lead in water a
      heterogeneous precipitate based ion-selective membrane electrode was developed by
      means of this composite cation exchanger as electroactive material. The membrane
      electrode is mechanically stable, with a quick response time, and can be operated
      over a wide pH range. The selectivity coefficients were determined by mixed
      solution method and revealed that the electrode is sensitive for Pb(II) in
      presence of interfering cations. The practical utility of this membrane electrode
      has been established by employing it as an indicator electrode in the
      potentiometric titration of Pb(II).

PMID- 20140083
TI  - Chromatographic and Spectral Analysis of Two Main Extractable Compounds Present
      in Aqueous Extracts of Laminated Aluminum Foil Used for Protecting LDPE-Filled
      Drug Vials.
AB  - Laminated aluminum foils are increasingly being used to protect drug products
      packaged in semipermeable containers (e.g., low-density polyethylene (LDPE)) from
      degradation and/or evaporation. The direct contact of such materials with primary
      packaging containers may potentially lead to adulteration of the drug product by
      extractable or leachable compounds present in the closure system. In this paper,
      we described a simple and reliable HPLC method for analysis of an aqueous extract
      of laminated aluminum foil overwrap used for packaging LDPE vials filled with
      aqueous pharmaceutical formulations. By means of combined HPLC-UV, GC/MS,
      LC/MS/MS, and NMR spectroscopy, the two major compounds detected in the aqueous
      extracts of the representative commercial overwraps were identified as cyclic
      oligomers with molecular weights of 452 and 472 and are possibly formed from poly
      condensation of the adhesive components, namely, isophthalic acid, adipic acid,
      and diethylene glycol. Lower molecular weight compounds that might be associated
      with the "building blocks" of these compounds were not detected in the aqueous
      extracts.

PMID- 20140085
TI  - The effect of orthology and coregulation on detecting regulatory motifs.
AB  - BACKGROUND: Computational de novo discovery of transcription factor binding sites
      is still a challenging problem. The growing number of sequenced genomes allows
      integrating orthology evidence with coregulation information when searching for
      motifs. Moreover, the more advanced motif detection algorithms explicitly model
      the phylogenetic relatedness between the orthologous input sequences and thus
      should be well adapted towards using orthologous information. In this study, we
      evaluated the conditions under which complementing coregulation with orthologous
      information improves motif detection for the class of probabilistic motif
      detection algorithms with an explicit evolutionary model. METHODOLOGY: We
      designed datasets (real and synthetic) covering different degrees of coregulation
      and orthologous information to test how well Phylogibbs and Phylogenetic sampler,
      as representatives of the motif detection algorithms with evolutionary model
      performed as compared to MEME, a more classical motif detection algorithm that
      treats orthologs independently. RESULTS AND CONCLUSIONS: Under certain conditions
      detecting motifs in the combined coregulation-orthology space is indeed more
      efficient than using each space separately, but this is not always the case.
      Moreover, the difference in success rate between the advanced algorithms and MEME
      is still marginal. The success rate of motif detection depends on the complex
      interplay between the added information and the specificities of the applied
      algorithms. Insights in this relation provide information useful to both
      developers and users. All benchmark datasets are available at
      http://homes.esat.kuleuven.be/~kmarchal/Supplementary_Storms_Valerie_PlosONE.

PMID- 20140084
TI  - Keratin promoter based gene manipulation in the murine conducting airway.
AB  - Systems capable of targeting genetic manipulations to keratin-positive airway
      basal cells are more poorly developed than systems targeting other airway
      epithelial cell populations and this has likely hindered development of animal
      models of diseases such as lung squamous cell carcinoma. Although keratin
      promoter driven-Cre recombinase constructs are potentially useful for targeting
      these cells, these constructs have substantially higher activity in the skin and
      oral epithelium than in the airways. We developed a method for delivering RU486,
      the conditional activator of Cre recombinase progesterone receptor (CrePR) fusion
      proteins to the lung and then examined the activity of three keratin-driven CrePR
      constructs in the conducting airways. We also developed a technique for survival
      bronchioalveolar lavage on non-ventilated animals to examine the effects of the
      acetone/oil vehicle required to deliver RU486 to the lung. K5CrePR1 and K14CrePR1
      constructs differ only in the keratin promoter used to target CrePR1 expression
      while K5Cre*PR contains a truncated progesterone receptor designed to reduce
      RU486-independent Cre activity. While all three constructs demonstrate RU486
      inducible Cre activity in the conducting airways, both construct activity and
      tightness of regulation vary considerably. K5Cre*PR is the most tightly regulated
      Cre driver making it ideal for targeting somatic mutations to the airway
      epithelia while K5CrePR1 and K14CrePR1 may be better suited to studying diseases
      of the conducting airways where gene targeting of keratin expressing cells and
      their derivatives is desired.

PMID- 20140086
TI  - Genetic variation at selected SNPs in the leptin gene and association of alleles
      with markers of kidney disease in a Xhosa population of South Africa.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a significant public health problem
      that leads to end-stage renal disease (ESRD) with as many as 2 million people
      predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and
      leptin, the obesity hormone, correlates with body fat mass and markers of renal
      function. A number of clinical and experimental studies have suggested a link
      between serum leptin and kidney disease. We hypothesised that variants in the
      leptin gene (LEP) may be associated with markers of CKD in indigenous black
      Africans. METHODOLOGY/PRINCIPAL FINDINGS: Black South Africans of Xhosa (distinct
      cultural Bantu-speaking population) descent were recruited for the study and four
      common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653
      [ENSSNP5824596]) were analysed for genotype and haplotype association with urine
      albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR),
      Serum creatinine (Scr) and serum leptin level. In one of the four single
      nucleotide polymorphisms (SNPs) we examined, an association with the renal
      phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of
      the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and
      significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis.
      Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio
      in normotensive subjects (p = 0.0482). CONCLUSIONS/SIGNIFICANCE: These results
      suggest that genetic variations of the LEP may be associated with phenotypes that
      are markers of CKD in black Africans.

PMID- 20140087
TI  - Comprehensive identification and modified-site mapping of S-nitrosylated targets
      in prostate epithelial cells.
AB  - BACKGROUND: Although overexpression of nitric oxide synthases (NOSs) has been
      found associated with prostate diseases, the underlying mechanisms for NOS
      related prostatic diseases remain unclear. One proposed mechanism is related to
      the S-nitrosylation of key regulatory proteins in cell-signaling pathways due to
      elevated levels of NO in the prostate. Thus, our primary objective was to
      identify S-nitrosylated targets in an immortalized normal prostate epithelial
      cell line, NPrEC. METHODOLOGY/PRINCIPAL FINDINGS: We treated NPrEC with nitroso
      cysteine and used the biotin switch technique followed by gel-based separation
      and mass spectrometry protein identification (using the LTQ-Orbitrap) to discover
      S-nitrosylated (SNO) proteins in the treated cells. In parallel, we adapted a
      peptide pull-down methodology to locate the site(s) of S-nitrosylation on the
      protein SNO targets identified by the first technique. This combined approach
      identified 116 SNO proteins and determined the sites of modification for 82 of
      them. Over 60% of these proteins belong to four functional groups: cell
      structure/cell motility/protein trafficking, protein folding/protein
      response/protein assembly, mRNA splicing/processing/transcriptional regulation,
      and metabolism. Western blot analysis validated a subset of targets related to
      disease development (proliferating cell nuclear antigen, maspin, integrin beta4,
      alpha-catenin, karyopherin [importin] beta1, and elongation factor 1A1). We
      analyzed the SNO sequences for their primary and secondary structures, solvent
      accessibility, and three-dimensional structural context. We found that about 80%
      of the SNO sites that can be mapped into resolved structures are buried, of which
      approximately half have charged amino acids in their three-dimensional
      neighborhood, and the other half residing within primarily hydrophobic pockets.
      CONCLUSIONS/SIGNIFICANCE: We here identified 116 potential SNO targets and mapped
      their putative SNO sites in NPrEC. Elucidation of how this post-translational
      modification alters the function of these proteins should shed light on the role
      of NO in prostate pathologies. To our knowledge, this is the first report
      identifying SNO targets in prostate epithelial cells.

PMID- 20140088
TI  - Optimal waist-to-hip ratios in women activate neural reward centers in men.
AB  - Secondary sexual characteristics convey information about reproductive potential.
      In the same way that facial symmetry and masculinity, and shoulder-to-hip ratio
      convey information about reproductive/genetic quality in males, waist-to-hip
      ratio (WHR) is a phenotypic cue to fertility, fecundity, neurodevelopmental
      resources in offspring, and overall health, and is indicative of "good genes" in
      women. Here, using fMRI, we found that males show activation in brain reward
      centers in response to naked female bodies when surgically altered to express an
      optimal (approximately 0.7) WHR with redistributed body fat, but relatively
      unaffected body mass index (BMI). Relative to presurgical bodies, brain
      activation to postsurgical bodies was observed in bilateral orbital frontal
      cortex. While changes in BMI only revealed activation in visual brain substrates,
      changes in WHR revealed activation in the anterior cingulate cortex, an area
      associated with reward processing and decision-making. When regressing ratings of
      attractiveness on brain activation, we observed activation in forebrain
      substrates, notably the nucleus accumbens, a forebrain nucleus highly involved in
      reward processes. These findings suggest that an hourglass figure (i.e., an
      optimal WHR) activates brain centers that drive appetitive sociality/attention
      toward females that represent the highest-quality reproductive partners. This is
      the first description of a neural correlate implicating WHR as a putative honest
      biological signal of female reproductive viability and its effects on men's
      neurological processing.

PMID- 20140089
TI  - Conduction properties distinguish unmyelinated sympathetic efferent fibers and
      unmyelinated primary afferent fibers in the monkey.
AB  - BACKGROUND: Different classes of unmyelinated nerve fibers appear to exhibit
      distinct conductive properties. We sought a criterion based on conduction
      properties for distinguishing sympathetic efferents and unmyelinated, primary
      afferents in peripheral nerves. METHODOLOGY/PRINCIPAL FINDINGS: In anesthetized
      monkey, centrifugal or centripetal recordings were made from single unmyelinated
      nerve fibers in the peroneal or sural nerve, and electrical stimuli were applied
      to either the sciatic nerve or the cutaneous nerve endings, respectively. In
      centrifugal recordings, electrical stimulation at the sympathetic chain and
      dorsal root was used to determine the fiber's origin. In centrifugal recordings,
      sympathetic fibers exhibited absolute speeding of conduction to a single pair of
      electrical stimuli separated by 50 ms; the second action potential was conducted
      faster (0.61 0.16%) than the first unconditioned action potential. This was never
      observed in primary afferents. Following 2 Hz stimulation (3 min), activity
      dependent slowing of conduction in the sympathetics (8.6 0.5%) was greater than
      in one afferent group (6.7 0.5%) but substantially less than in a second afferent
      group (29.4 1.9%). In centripetal recordings, most mechanically-insensitive
      fibers also exhibited absolute speeding to twin pulse stimulation. The subset
      that did not show this absolute speeding was responsive to chemical stimuli
      (histamine, capsaicin) and likely consists of mechanically-insensitive afferents.
      During repetitive twin pulse stimulation, mechanosensitive afferents developed
      speeding, and speeding in sympathetic fibers increased. CONCLUSIONS/SIGNIFICANCE:
      The presence of absolute speeding provides a criterion by which sympathetic
      efferents can be differentiated from primary afferents. The differences in
      conduction properties between sympathetics and afferents likely reflect
      differential expression of voltage-sensitive ion channels.

PMID- 20140090
TI  - Sex and ethnic differences in 47 candidate proteomic markers of cardiovascular
      disease: the Mayo Clinic proteomic markers of arteriosclerosis study.
AB  - BACKGROUND: Cardiovascular disease (CVD) susceptibility differs between men and
      women and varies with ethnicity. This variability is not entirely explained by
      conventional CVD risk factors. We examined differences in circulating levels of
      47 novel protein markers of CVD in 2561 men and women of African-American (AA)
      and non-Hispanic White (NHW) ethnicity, enrolled at geographically distinct
      sites. METHODOLOGY/PRINCIPAL FINDINGS: Participants (1,324 AAs, mean age 63.5 y,
      71% women; 1,237 NHWs, mean age 58.9 y, 57% women) belonged to sibships
      ascertained on the basis of hypertension. Solid-phase immunoassays and
      immunoturbidometric, clot-based, chromogenic, and electrophoretic assays were
      used to measure the 47 protein markers in plasma or serum. Marker levels were log
      transformed and outliers were adjusted to within 4 SD. To identify markers
      independently associated with sex or ethnicity, we employed multivariable
      regression analyses that adjusted for conventional risk factors, prior history of
      CVD, medication use and lifestyle factors (physical activity, alcohol consumption
      and education). Generalized estimating equations were used to correct for
      intrafamilial correlations. After adjustment for the above covariates, female sex
      was associated with higher levels of 29 markers and lower levels of 6 markers.
      Female sex was independently associated with higher levels of several
      inflammatory markers as well as lipoproteins, adipokines, natriuretic peptides,
      vasoconstrictor peptides and markers of calcification and thrombosis. AA
      ethnicity was associated with higher levels of 19 markers and lower levels of 6
      markers, including higher levels of several inflammatory makers, higher leptin
      and lower adiponectin levels, lower levels of vasodilator-natriuretic peptides,
      higher levels of vasoconstrictor-antidiuretic peptides and markers of
      calcification and thrombosis. CONCLUSIONS/SIGNIFICANCE: Plasma levels of several
      novel protein markers of CVD differ significantly in the context of sex and
      ethnicity. These results have implications for individualized CVD risk
      assessment.

PMID- 20140091
TI  - Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis
      patients correlates with severe disease manifestations.
AB  - BACKGROUND: Sarcoidosis is a poorly understood chronic inflammatory condition.
      Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis,
      however previous reports suggest that circulating lymphocyte counts are low in
      some patients with the disease. The goal of this study was to evaluate lymphocyte
      subsets in peripheral blood in a cohort of sarcoidosis patients to determine the
      prevalence, severity, and clinical features associated with lymphopenia in major
      lymphocyte subsets. METHODOLOGY/PRINCIPAL FINDINGS: Lymphocyte subsets in 28
      sarcoid patients were analyzed using flow cytometry to determine the percentage
      of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally
      low CD4, CD8, or CD19 counts (p<4x10(-10)). Lymphopenia was profound in some
      cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and
      CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57,
      p = 0.0017), and 10 patients had low counts in all three subsets. Patients with
      severe organ system involvement including neurologic, cardiac, ocular, and
      advanced pulmonary disease had lower lymphocyte subset counts as a group than
      those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026,
      CD19 p = 0.033). No significant relationships were observed between various
      medical therapies and lymphocyte counts, and lymphopenia was present in patients
      who were not receiving any medical therapy. CONCLUSIONS/SIGNIFICANCE: Significant
      lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis
      patients and correlated with disease severity. Our findings suggest that
      lymphopenia relates more to disease pathology than medical treatment.

PMID- 20140092
TI  - Active fragments from pro- and antiapoptotic BCL-2 proteins have distinct
      membrane behavior reflecting their functional divergence.
AB  - BACKGROUND: The BCL-2 family of proteins includes pro- and antiapoptotic members
      acting by controlling the permeabilization of mitochondria. Although the
      association of these proteins with the outer mitochondrial membrane is crucial
      for their function, little is known about the characteristics of this
      interaction. METHODOLOGY/PRINCIPAL FINDINGS: Here, we followed a reductionist
      approach to clarify to what extent membrane-active regions of homologous BCL-2
      family proteins contribute to their functional divergence. Using isolated
      mitochondria as well as model lipid Langmuir monolayers coupled with Brewster
      Angle Microscopy, we explored systematically and comparatively the membrane
      activity and membrane-peptide interactions of fragments derived from the central
      helical hairpin of BAX, BCL-xL and BID. The results show a connection between the
      differing abilities of the assayed peptide fragments to contact, insert,
      destabilize and porate membranes and the activity of their cognate proteins in
      programmed cell death. CONCLUSION/SIGNIFICANCE: BCL-2 family-derived pore-forming
      helices thus represent structurally analogous, but functionally dissimilar
      membrane domains.

PMID- 20140093
TI  - Characterization of a Chinese hamster ovary cell mutant having a mutation in
      elongation factor-2.
AB  - Retroviral insertional mutagenesis provides an effective forward genetic method
      for identifying genes involved in essential cellular pathways. A Chinese hamster
      ovary cell line mutant resistant to several bacterial ADP-ribosylating was
      obtained by this approach. The toxins used catalyze ADP-ribosylation of
      eukaryotic elongation factor 2 (eEF-2), block protein synthesis, and cause cell
      death. Strikingly, in the CHO PR328 mutant cells, the eEF-2 substrate of these
      ADP-ribosylating toxins was found to be modified, but the cells remained viable.
      A systematic study of these cells revealed the presence of a structural mutation
      in one allele of the eEF-2 gene. This mutation, Gly717Arg, is close to His715,
      the residue that is modified to become diphthamide. This Arg substitution
      prevents diphthamide biosynthesis at His715, rendering the mutated eEF-2 non
      responsive to ADP-ribosylating toxins, while having no apparent effect on protein
      synthesis. Thus, CHO PR328 cells are heterozygous, having wild type and mutant
      eEF-2 alleles, with the latter allowing the cells to survive even in the presence
      of ADP-ribosylating toxins. Here, we report the comprehensive characterization of
      these cells.

PMID- 20140094
TI  - Prevalence and risk factors for trachoma in central and southern Malawi.
AB  - BACKGROUND: Trachoma, one of the neglected tropical diseases is suspected to be
      endemic in Malawi. OBJECTIVES: To determine the prevalence of trachoma and
      associated risk factors in central and southern Malawi. METHODOLOGY/PRINCIPAL
      FINDINGS: A population based survey conducted in randomly selected clusters in
      Chikwawa district (population 438,895), southern Malawi and Mchinji district
      (population 456,558), central Malawi. Children aged 1-9 years and adults aged 15
      and above were assessed for clinical signs of trachoma. In total, 1010 households
      in Chikwawa and 1016 households in Mchinji districts were enumerated within 108
      clusters (54 clusters in each district). A total of 6,792 persons were examined
      for ocular signs of trachoma. The prevalence of trachomatous inflammation,
      follicular (TF) among children aged 1-9 years was 13.6% (CI 11.6-15.6) in
      Chikwawa and 21.7% (CI 19.5-23.9) in Mchinji districts respectively. The
      prevalence of trachoma trichiasis (TT) in women and men aged 15 years and above
      was 0.6% (CI 0.2-0.9) in Chikwawa and 0.3% (CI 0.04-0.6) in Mchinji respectively.
      The presence of a dirty face was significantly associated with trachoma
      follicular (TF) in both Chikwawa and Mchinji districts (P<0.001).
      CONCLUSION/SIGNIFICANCE: Prevalence rates of trachoma follicles (TF) in Central
      and Southern Malawi exceeds the WHO guidelines for the intervention with mass
      antibiotic distribution (TF>10%), and warrants the trachoma SAFE control strategy
      to be undertaken in Chikwawa and Mchinji districts.

PMID- 20140095
TI  - How cholesterol constrains glycolipid conformation for optimal recognition of
      Alzheimer's beta amyloid peptide (Abeta1-40).
AB  - Membrane lipids play a pivotal role in the pathogenesis of Alzheimer's disease,
      which is associated with conformational changes, oligomerization and/or
      aggregation of Alzheimer's beta-amyloid (Abeta) peptides. Yet conflicting data
      have been reported on the respective effect of cholesterol and glycosphingolipids
      (GSLs) on the supramolecular assembly of Abeta peptides. The aim of the present
      study was to unravel the molecular mechanisms by which cholesterol modulates the
      interaction between Abeta(1-40) and chemically defined GSLs (GalCer, LacCer, GM1,
      GM3). Using the Langmuir monolayer technique, we show that Abeta(1-40)
      selectively binds to GSLs containing a 2-OH group in the acyl chain of the
      ceramide backbone (HFA-GSLs). In contrast, Abeta(1-40) did not interact with GSLs
      containing a nonhydroxylated fatty acid (NFA-GSLs). Cholesterol inhibited the
      interaction of Abeta(1-40) with HFA-GSLs, through dilution of the GSL in the
      monolayer, but rendered the initially inactive NFA-GSLs competent for Abeta(1-40)
      binding. Both crystallographic data and molecular dynamics simulations suggested
      that the active conformation of HFA-GSL involves a H-bond network that restricts
      the orientation of the sugar group of GSLs in a parallel orientation with respect
      to the membrane. This particular conformation is stabilized by the 2-OH group of
      the GSL. Correspondingly, the interaction of Abeta(1-40) with HFA-GSLs is
      strongly inhibited by NaF, an efficient competitor of H-bond formation. For NFA
      GSLs, this is the OH group of cholesterol that constrains the glycolipid to adopt
      the active L-shape conformation compatible with sugar-aromatic CH-pi stacking
      interactions involving residue Y10 of Abeta(1-40). We conclude that cholesterol
      can either inhibit or facilitate membrane-Abeta interactions through fine tuning
      of glycosphingolipid conformation. These data shed some light on the complex
      molecular interplay between cell surface GSLs, cholesterol and Abeta peptides,
      and on the influence of this molecular ballet on Abeta-membrane interactions.

PMID- 20140096
TI  - Replication, pathogenesis and transmission of pandemic (H1N1) 2009 virus in non
      immune pigs.
AB  - The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised
      important questions, including origin and host range [1], [2]. Two of the three
      pandemics in the last century resulted in the spread of virus to pigs (H1N1,
      1918; H3N2, 1968) with subsequent independent establishment and evolution within
      swine worldwide [3]. A key public and veterinary health consideration in the
      context of the evolving pandemic is whether the H1N1/09 virus could become
      established in pig populations [4]. We performed an infection and transmission
      study in pigs with A/California/07/09. In combination, clinical, pathological,
      modified influenza A matrix gene real time RT-PCR and viral genomic analyses have
      shown that infection results in the induction of clinical signs, viral
      pathogenesis restricted to the respiratory tract, infection dynamics consistent
      with endemic strains of influenza A in pigs, virus transmissibility between pigs
      and virus-host adaptation events. Our results demonstrate that extant H1N1/09 is
      fully capable of becoming established in global pig populations. We also show the
      roles of viral receptor specificity in both transmission and tissue tropism.
      Remarkably, following direct inoculation of pigs with virus quasispecies
      differing by amino acid substitutions in the haemagglutinin receptor-binding
      site, only virus with aspartic acid at position 225 (225D) was detected in nasal
      secretions of contact infected pigs. In contrast, in lower respiratory tract
      samples from directly inoculated pigs, with clearly demonstrable pulmonary
      pathology, there was apparent selection of a virus variant with glycine (225G).
      These findings provide potential clues to the existence and biological
      significance of viral receptor-binding variants with 225D and 225G during the
      1918 pandemic [5].

PMID- 20140097
TI  - Differential expression of proteoglycans in tissue remodeling and
      lymphangiogenesis after experimental renal transplantation in rats.
AB  - BACKGROUND: Chronic transplant dysfunction explains the majority of late renal
      allograft loss and is accompanied by extensive tissue remodeling leading to
      transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix
      proteoglycans mediate cell-cell and cell-matrix interactions and play key roles
      in tissue remodeling. The aim of this study was to characterize differential
      heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in
      transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal
      allografts with chronic transplant dysfunction. METHODS: Renal allografts were
      transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark
      Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served
      as controls. Allograft and isograft recipients were sacrificed 66 and 81 days
      (mean) after transplantation, respectively. Heparan sulfate proteoglycan
      (collXVIII, perlecan and agrin) and chondroitin sulfate proteoglycan (versican)
      expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium,
      respectively) expression were (semi-) quantitatively analyzed using
      immunofluorescence. FINDINGS: Arteries with transplant vasculopathy and sclerotic
      glomeruli in allografts displayed pronounced neo-expression of collXVIII and
      perlecan. In contrast, in interstitial fibrosis expression of the chondroitin
      sulfate proteoglycan versican dominated. In the cortical tubular basement
      membranes in both iso- and allografts, induction of collXVIII was detected.
      Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts
      and non-transplanted controls), which was associated with induced perlecan
      expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to
      isografts and non-transplanted controls, respectively). Both the magnitude of
      lymphangiogenesis and perlecan expression correlated with severity of
      interstitial fibrosis and impaired graft function. INTERPRETATION: Our results
      reveal that changes in the extent of expression and the type of proteoglycans
      being expressed are tightly associated with tissue remodeling after renal
      transplantation. Therefore, proteoglycans might be potential targets for clinical
      intervention in renal chronic transplant dysfunction.

PMID- 20140098
TI  - Antigenic characterization of recombinant hemagglutinin proteins derived from
      different avian influenza virus subtypes.
AB  - Since the advent of highly pathogenic variants of avian influenza virus (HPAIV),
      the main focus of avian influenza research has been the characterization and
      detection of HPAIV hemagglutinin (HA) from H5 and H7 subtypes. However, due to
      the high mutation and reassortation rate of influenza viruses, in theory any
      influenza strain may acquire increased pathogenicity irrespective of its subtype.
      A comprehensive antigenic characterization of influenza viruses encompassing all
      16 HA and 9 neuraminidase subtypes will provide information useful for the design
      of differential diagnostic tools, and possibly, vaccines. We have expressed
      recombinant HA proteins from 3 different influenza virus HA subtypes in the
      baculovirus system. These proteins were used to generate polyclonal rabbit
      antisera, which were subsequently employed in epitope scanning analysis using
      peptide libraries spanning the entire HA. Here, we report the identification and
      characterization of linear, HA subtype-specific as well as inter subtype
      conserved epitopes along the HA proteins. Selected subtype-specific epitopes were
      shown to be suitable for the differentiation of anti-HA antibodies in an ELISA.

PMID- 20140099
TI  - Sleep deprivation impairs object-selective attention: a view from the ventral
      visual cortex.
AB  - BACKGROUND: Most prior studies on selective attention in the setting of total
      sleep deprivation (SD) have focused on behavior or activation within fronto
      parietal cognitive control areas. Here, we evaluated the effects of SD on the top
      down biasing of activation of ventral visual cortex and on functional
      connectivity between cognitive control and other brain regions.
      METHODOLOGY/PRINCIPAL FINDINGS: Twenty-three healthy young adult volunteers
      underwent fMRI after a normal night of sleep (RW) and after sleep deprivation in
      a counterbalanced manner while performing a selective attention task. During this
      task, pictures of houses or faces were randomly interleaved among scrambled
      images. Across different blocks, volunteers responded to house but not face
      pictures, face but not house pictures, or passively viewed pictures without
      responding. The appearance of task-relevant pictures was unpredictable in this
      paradigm. SD resulted in less accurate detection of target pictures without
      affecting the mean false alarm rate or response time. In addition to a reduction
      of fronto-parietal activation, attending to houses strongly modulated
      parahippocampal place area (PPA) activation during RW, but this attention-driven
      biasing of PPA activation was abolished following SD. Additionally, SD resulted
      in a significant decrement in functional connectivity between the PPA and two
      cognitive control areas, the left intraparietal sulcus and the left inferior
      frontal lobe. CONCLUSIONS/SIGNIFICANCE: SD impairs selective attention as
      evidenced by reduced selectivity in PPA activation. Further, reduction in fronto
      parietal and ventral visual task-related activation suggests that it also affects
      sustained attention. Reductions in functional connectivity may be an important
      additional imaging parameter to consider in characterizing the effects of sleep
      deprivation on cognition.

PMID- 20140100
TI  - Antidepressants and suicide in adolescents and adults: a public health experiment
      with unintended consequences?

PMID- 20140101
TI  - A review of cardiovascular risks associated with medications used to treat type-2
      diabetes mellitus.

PMID- 20140102
TI  - American society of clinical oncology, 45th annual meeting.

PMID- 20140103
TI  - Pharmaceutical approval update.

PMID- 20140104
TI  - Chart Review: Prophylaxis of Pneumocystis Pneumonia at a Large Metropolitan HIV
      Clinic.

PMID- 20140105
TI  - Will pharma twitter?

PMID- 20140106
TI  - Warfarin pharmacogenomics.
AB  - Warfarin, an anticoagulant, is used to prevent and treat thromboembolic disease.
      One of the drawbacks of this agent, also known as Coumadin (Bristol-Myers
      Squibb), is that it is difficult to administer at the correct dose as a result of
      its narrow therapeutic index, its tendency to cause bleeding, and the individual
      variability in patient response. Achieving safe and effective doses of warfarin
      therapy is both an urgent and important concern for many clinicians.Recent
      research has focused on single-nucleotide polymorphisms (SNPs) of genes that
      encode two proteins: the cytochrome P450 2C9 enzyme and VKORC1 (vitamin K epoxide
      reductase complex). Studies suggest that CYP 2C9 influences warfarin metabolism,
      whereas VKORC1 plays a role in the pharmacodynamic response in expression of the
      enzymatic target of warfarin. Patients who carry CYP 2C9*2 and CYP 2C9*3 alleles
      tend to require lower warfarin maintenance doses because of their slowed
      metabolism compared with patients who carry the "wild-type" allele. Patients who
      carry the VKORC1 A haplotype tend to require lower wafarin maintenance doses as a
      result of a decreased expression of messenger RNA (mRNA), which produces the
      proteins necessary for the formation of VKORC1.

PMID- 20140107
TI  - Off-label drug information: regulation, distribution, evaluation, and related
      controversies.

PMID- 20140108
TI  - Medical design and manufacturing East conference and exhibition 2009: marketing
      medical devices in the United States.

PMID- 20140109
TI  - American diabetes association and European league against rheumatism.

PMID- 20140110
TI  - Down to the wire on health care reform: stakes high for pharmaceutical industry
      sectors.

PMID- 20140111
TI  - Thiazolidinediones and cardiovascular events in high-risk patients with type-2
      diabetes mellitus: a comparison with other oral antidiabetic agents.
AB  - CONTEXT.: The use of thiazolidinediones (TZDs) in patients with type-2 diabetes
      mellitus appears to be associated with an increased risk of myocardial infarction
      (MI) compared with placebo or other oral antidiabetic drug regimens. OBJECTIVE.:
      We conducted a study to investigate whether there was a difference in the risk of
      acute MI and hemorrhagic and non-hemorrhagic stroke between specific TZDs, namely
      rosiglitazone maleate (Avandia) and pioglitazone (Actos), and other oral
      antidiabetic agents in a high-risk, largely underrepresented and largely minority
      Medicaid population. STUDY DESIGN, SETTING, AND PATIENTS.: We analyzed patient
      encounter data using propensity-scoring methods and logistic regression to
      compare the risk of cardiovascular (CV) events in patients with type-2 diabetes
      in a high-risk population. MAIN OUTCOME MEASURES.: Outcomes were identified
      through International Classification of Disease (ICD-9) codes 410-411 for acute
      MI; 430-438 for stroke; and revenue (emergency department) codes 450-459 in the
      case of MI. RESULTS.: Using retrospective medical encounter and prescription data
      analyses, we found that rosiglitazone, compared with other oral antidiabetic
      agents, was associated with an increased rate of CV events by 20% in a high-risk
      cohort of diabetic patients. Neither pioglitazone nor the TZD drug class as a
      whole was associated with an increased CV risk. CONCLUSION.: Rosiglitazone was
      associated with a significant increase in CV events (MI and stroke) among high
      risk patients with type-2 diabetes, whereas pioglitazone was not. We recommend
      further research to capture risk factors that were not observed in our encounter
      data.

PMID- 20140112
TI  - Therapies for insomnia and comorbid chronic obstructive pulmonary disease with a
      focus on ramelteon (rozerem).

PMID- 20140113
TI  - Pharmaceutical approval update.

PMID- 20140114
TI  - Should Your Genes Be Subject To Patents? No, Says a New ACLU Lawsuit.

PMID- 20140115
TI  - Prescribing trends with levalbuterol (xopenex) at a community hospital.

PMID- 20140116
TI  - Erlotinib (tarceva) for the treatment of non-small-cell lung cancer and
      pancreatic cancer.
AB  - Erlotinib (Tarceva) is a small-molecule, orally dosed, anti-cancer drug that
      inhibits the epidermal growth factor receptor. Randomized, controlled clinical
      studies have demonstrated that erlotinib significantly improved survival in
      patients with previously treated non-small-cell lung cancer and, in combination
      with chemotherapy, in patients with untreated pancreatic cancer. In this article,
      we describe the clinical evidence and value of erlotinib as a therapy for non
      small-cell lung cancer and pancreatic cancer and discuss ongoing clinical studies
      to optimize its use in various settings and to identify appropriate patient
      populations.

PMID- 20140118
TI  - Pharmaceutical approval update.

PMID- 20140117
TI  - European society of cardiology, 2009 congress and a comparison of two asthma
      medications.

PMID- 20140119
TI  - Psychiatry investigation : the next step forward.

PMID- 20140120
TI  - Imaging improves diagnosis of dementia with lewy bodies.
AB  - Dementia with Lewy bodies (DLB) is the second most common cause of degenerative
      dementia after Alzheimer's disease (AD), and is clinically characterized by the
      progressive cognitive decline with fluctuations in cognition and alertness,
      recurrent visual hallucinations and Parkinsonism. Once these characteristic
      symptoms of DLB emerge, discriminating it from AD is relatively easy. However, in
      the early disease stages, the clinical symptoms of various types of dementias
      largely overlap and it is difficult to distinguish DLB from other
      neurodegenerative dementias based on clinical manifestations alone. To increase
      the accuracy of antemortem diagnosis of DLB, the latest diagnostic criteria
      incorporate findings from 123I-metaiodobenzylguanidine (MIBG) myocardial
      scintigraphy, or from neuroimaging such as computed tomography (CT), magnetic
      resonance imaging (MRI), single photon emission computed tomography (SPECT), and
      positron emission tomography (PET). In the present guidelines, decreased dopamine
      transporter uptake revealed by SPECT or PET receives the greatest importance
      among various neuroimaging findings and is listed as one of the suggestive
      features. Supportive features that commonly present but are not proven to have
      diagnostic specificity include relatively-preserved medial-temporal-lobe
      structures, occipital hypoperfusion, and abnormal MIBG myocardial scintigraphy.
      In this paper, we review the major findings on various neuroimaging modalities
      and discuss the clinical usefulness of them for the diagnosis of DLB. Although
      there is not enough evidence to reach the conclusion, considering the
      accessibility in clinical practice, in our personal views, we recommend the use
      of brain-perfusion SPECT and MIBG myocardial scintigraphy to improve the
      diagnosis of DLB.

PMID- 20140121
TI  - The associations of coping mechanism with arterial stiffness in hwa-byung
      patients.
AB  - OBJECTIVE: The goal of this study is to assess the relationship between stress
      coping mechanisms and the risk of atherosclerosis in patients with Hwa-Byung.
      METHODS: The Korean version of the Ways of Coping Checklist (WOCC) was
      administered to 50 patients with Hwa-Byung (49.1+/-10.1 years, 6 males). Brachial
      ankle pulse wave velocity (baPWV) and serum cholesterol level were assessed in
      all participants. RESULTS: After controlling for age, sex, diagnosis of
      hypertension, Body Mass Index (BMI), and serum cholesterol level, the score of
      seeking social support in coping strategies was negatively correlated with right
      and left baPWV (r=-0.356, p=0.016; r=-0.373, p=0.012, respectively). In addition,
      the score of active coping mechanism was negatively correlated with both sides of
      baPWV (r=-0.383, p=0.009; r=-0.389, p=0.008, respectively). CONCLUSION: The
      seeking social support and active coping mechanism were inversely related to the
      severity of arterial stiffness in Hwa-Byung patients. Therefore, our result may
      suggest a possibility that coping strategies in Hwa-Byung patients are associated
      with the risk of atherosclerosis.

PMID- 20140122
TI  - The effect of cognitive behavior therapy-based psychotherapy applied in a forest
      environment on physiological changes and remission of major depressive disorder.
AB  - OBJECTIVE: Psychotherapeutic intervention combined with pharmacotherapy is
      helpful for achieving remission of depressive disorder. We developed and tested
      the effect of cognitive behavior therapy (CBT)-based psychotherapy applied in a
      forest environment on major depressive disorder. METHODS: We performed 4 sessions
      during 4 weeks (3 hours/session) in patients with major depressive disorder
      during pharmacotherapy. For the forest group, sessions were performed in the
      forest; for the hospital group, sessions were performed in the hospital. The
      control group was treated with the usual outpatient management. RESULTS: A total
      of 63 patients completed the study: 23 in the forest group, 19 in the hospital
      group, and 21 in the control group. Hamilton Rating Scales for Depression (HRSD)
      scores of the forest group were significantly decreased after 4 sessions compared
      with controls. Montgomery-Asberg Depression Rating Scales (MADRS) scores of the
      forest group were significantly decreased compared with both the hospital group
      and the controls. The remission rate (7 and below in HRSD) of the forest group
      was 61% (14/23), significantly higher than both the hospital group (21%, 4/19)
      and the controls (5%, 1/21). In heart rate variability (HRV) analysis, some
      measurements representing HRV and parasympathetic nerve tone were increased in
      the forest group after 4 sessions. The salivary cortisol levels of the forest
      group were significantly decreased. CONCLUSION: CBT-based psychotherapy applied
      in the forest environment was helpful in the achievement of depression remission,
      and its effect was superior to that of psychotherapy performed in the hospital
      and the usual outpatient management. A good environment such as a forest helps
      improve the effect of psychotherapeutic intervention because it includes various
      natural instruments and facilitators in the treatment of depression.

PMID- 20140123
TI  - Association between Painful Physical Symptoms and Clinical Outcomes in Korean
      Patients with Major Depressive Disorder: A Three-Month Observational Study.
AB  - OBJECTIVE: This paper aims to examine the association between painful physical
      symptoms (PPS) and major depressive disorder (MDD) in a naturalistic clinical
      practice setting within a Korean population. METHODS: Patients with acute MDD
      that joined a multicountry, observational, three-month study in six Asian
      countries and regions were classified as PPS+ (mean score >/=2) and PPS- (mean
      score <2) using the modified Somatic Symptom Inventory. In this analysis, we
      report the results from the Korean subset, where depression severity was assessed
      using the Clinical Global Impression of Severity (CGI-S) scale and 17-item
      Hamilton Depression Rating Scale (HAMD(17)). Pain severity was measured using a
      visual analogue scale (VAS), while the EuroQoL (EQ-5D) assessed patient well
      being. RESULTS: Of 198 patients, 45.96% (91/198) of patients were classified as
      PPS+, of which 78.02% (71/91) were women. PPS+ patients had significantly more
      severe depression at baseline {CGI-S score, mean [standard deviation (SD)], PPS+:
      5.09 [0.79]; PPS-: 4.63 [0.76]; p<0.001; HAMD(17) total score, mean [SD], PPS+:
      24.34 [5.24]; PPS-: 20.76 [5.12]; p<0.001} and poorer quality of life [EQ-5D
      overall health state, mean (SD), PPS+: 39.37 (20.52); PPS-: 51.27 [20.78];
      p<0.001] than PPS- patients. Both groups improved significantly (p<0.001) in
      depression and pain severity outcomes, as well as quality of life by endpoint,
      but no significant within-group baseline-to-endpoint change wase observed.
      CONCLUSION: The frequency of PPS was common in Korean patients with MDD, and was
      associated with more severe depression, poorer quality of life, and a trend
      towards poorer clinical outcome.

PMID- 20140125
TI  - Validation Study of Kim's Smoking Cessation Motivation Scale and Its Predictive
      Implications for Smoking Cessation.
AB  - OBJECTIVE: The purpose of this study was to develop a scale to measure motivation
      for smoking cessation. Motivation is known to be important for success of smoking
      cessation. The reliability of the scale was assessed and its predictive validity
      for smoking cessation was evaluated. METHODS: We recruited 333 men aged 20 to 70
      that visited smoking cessation clinics at seven public health centers. The
      demographic characteristics were recorded and the Korean version of Stages of
      Readiness for Change and Eagerness for Treatment Scale for Smoking (K-SO-CRATES
      S) performed. A smoking cessation motivation scale was developed with 10
      questions based on the theory of motivation enhancement therapy. RESULTS: The
      motivation scale was composed of four subscales based on the factor analysis;
      each subscale had an adequate degree of internal consistency. In addition, the
      newly developed scale had a high degree of validity based on its significant
      correlation with the smoking version of SOCRATES. Moreover, the precontemplation
      level of motivation was found to significantly predict the success of smoking
      cessation. And one of the subscales of the Korean Nicotine Dependence Syndrome
      Scale (K-NDSS), stereotypy which also significantly predicted the success of
      smoking cessation, significantly correlated with the preparation 1 and 2 level of
      motivation. CONCLUSION: The smoking cessation motivation scale with 10 questions
      that was developed in this study was a highly reliable and valid scale for the
      prediction of success for smoking cessation for those who wanted to stop smoking.

PMID- 20140124
TI  - Depressive Symptoms and Brain Metabolite Alterations in Subjects at Ultra-high
      Risk for Psychosis: A Preliminary Study.
AB  - OBJECTIVE: Recent neuroimaging studies have suggested that brain changes occur in
      subjects at ultra-high risk (UHR) for psychosis while experiencing prodromal
      symptoms, among which depression may increase the risk of developing a psychotic
      disorder. The goal of this study is to examine brain metabolite levels in the
      anterior cingulate cortex, the left dorsolateral prefrontal cortex and the left
      thalamus in subjects at UHR for psychosis and to compare brain metabolite levels
      between the UHR subjects with comorbid major depressive disorder and healthy
      controls. METHODS: Proton magnetic resonance spectroscopy was used to examine
      brain metabolite levels. Twenty UHR subjects and 20 age- and intelligence
      quotient (IQ)-matched healthy controls were included in this study. RESULTS:
      Overall, no significant differences were observed in any metabolite between the
      UHR and healthy control group. However, UHR subjects with major depressive
      disorder showed significantly higher myo-inositol (Ins) levels in the left
      thalamus, compared to the healthy control. CONCLUSION: Our results demonstrate
      that increased thalamic Ins level is associated with prodromal depressive
      symptoms. Further longitudinal follow-up studies with larger UHR sample sizes are
      required to investigate the function of Ins concentrations as a biomarker of
      vulnerability to psychosis.

PMID- 20140126
TI  - Perinatal and familial risk factors are associated with full syndrome and
      subthreshold attention-deficit hyperactivity disorder in a korean community
      sample.
AB  - OBJECTIVE: The objective of this study was to examine the effect of perinatal and
      familial risk factors on full syndrome and subthreshold attention
      deficit/hyperactivity disorder (ADHD) among Korean children and adolescents.
      METHODS: A sample of 2,673 students was randomly selected from 19 representative
      schools in Seoul, Korea. The parents of the students completed the Diagnostic
      Interview Schedule for Children-version IV (DISC-IV), as well as questionnaires
      on perinatal and familial risk factors. RESULTS: Maternal stress and alcohol use
      during pregnancy, parental marital discord, parental separation or divorce,
      changes in primary caregivers, and notbreastfeeding were significantly associated
      with full syndrome ADHD; however, maternal stress during pregnancy was the only
      variable that differentiated subthreshold ADHD from non-ADHD. CONCLUSION: Our
      results provide evidence the perinatal and familial risk factors contribute to
      the development of ADHD in Korea children and adolescents, and suggest that these
      perinatal and familial risk factors are more closely related to full syndrome
      than to subthreshold ADHD.

PMID- 20140127
TI  - Comparative Analysis of Cognitive Function in Schizophrenia with and without
      Obsessive Compulsive Disorder.
AB  - OBJECTIVE: We investigated the neurocognitive deficits in schizophrenic patients
      with and without obsessive-compulsive disorder (OCD). METHODS: We grouped 27
      patients as either obsessive-compulsive or non-obsessive-compulsive based on the
      presence of OCD. The two groups completed the Yale-Brown Obsessive-Compulsive
      Scale (Y-BOCS), Positive and Negative Symptom Scale (PANSS), and Hamilton
      Depression Scale. The intelligence quotient (IQ) was tested using the Korean
      Wechsler Adult Intelligence Scale. The memory quotient (MQ) was tested using the
      Korean-Auditory Verbal Learning and Korean-Complex Figure Test. The executive
      intelligence quotient (EIQ) was determined using the Kims executive intelligence
      test (EXIT). RESULTS: Ten of the 27 patients had OCD. The compulsion score of Y
      BOCS was positively correlated with positive symptoms, negative symptoms, and the
      total scores of PANSS. The OCD-schizophrenia patients had higher IQs. No
      difference was found in MQ. Although the EIQ did not differ between the two
      groups, the OCD-schizophrenia patients performed better at the Stroop
      interference and verbal fluency tests, which was highly dependent on executive
      function. CONCLUSION: Our findings suggest that OCD may have a protective effect
      on some cognitive function, at least in relatively early stage of illness.
      Moreover, based on clinical, neurocognitive features, schizophrenia with OCD
      could be considered as a distinct subtype of schizophrenia.

PMID- 20140128
TI  - The pNNx Heart Rate Variability Statistics: An Application to Neuroautonomic
      Dysfunction of Clozapine-Treated Subjects.
AB  - OBJECTIVE: The percentage of successive normal cardiac interbeat intervals
      greater than 50 msec (pNN50) is a widely used heart rate variability measure,
      which is useful in identifying the neuroautonomic dysfunction of psychiatric
      disorders. However, pNN50 is only one member of a larger family of pNNx
      statistics, where x is greater than 0 msec. The potential application of the
      general pNNx statistics has not yet been explored in the psychiatric field. The
      authors examined the pNNx statistics in clozapine-treated subjects and normal
      controls to evaluate the usefulness of the general pNNx statistics. METHODS:
      Sixty-one schizophrenic patients treated with clozapine and fifty-nine normal
      controls were evaluated. Probability values for the differences between the
      groups at each pNN value (range: pNN1-pNN100) were calculated using data obtained
      from a 30-minute electrocardiogram. RESULTS: The conventional pNN50 and pNNx
      values with x<50 msec were all significantly lower in the patient group (p<0.05).
      The distinction between the two groups was more prominent at pNN values less than
      50 msec than that observed at pNN50. The maximum separation between groups
      occurred at pNN5 (68.2+/-19.1 vs. 22.5+/-20.5, p<10(-22)). CONCLUSION: The pNNx
      with x<50 msec provided more robust discrimination between the groups than the
      conventional pNN50, suggesting the importance of analyzing very small variations
      of interbeat interval in discriminating normal and pathological heart rate
      patterns. The results also suggest that the general pNNx statistics may be
      applied and useful in evaluating the neuroautonomic dysfunction in patients
      treated with clozapine, complementing the traditionally computed pNN50 value.

PMID- 20140129
TI  - Decreased serum brain-derived neurotrophic factor levels in elderly korean with
      dementia.
AB  - OBJECTIVE: The primary purpose of this study was to investigate the differences
      in the serum brain-derived neurotrophic factor (BDNF) level between elderly
      Korean people over 65 years with and without dementia. METHODS: 171 individuals
      over 65 years were enrolled in this study. Screening for cognitive impairments
      was carried out using the Mini-Mental Status Examination-Korean version (MMSE
      KC). One hundred thirty-two subjects scored below 1.5 standard deviations (SD) of
      the mean MMSE-KC score, and these were evaluated using the Consortium to
      Establish a Registry for Alzheimer's Disease, Korean version (CERAD-K) and the
      Geriatric Depression Scale (GDS). The Clinical Dementia Rating Scale (CDRS) and
      the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM
      IV) diagnostic criteria were used for further evaluation. Subjects with a CDRS
      score of 1 or higher were classified as having Alzheimer's disease (AD), and
      subjects with a CDRS score of 0.5 were classified as having a mild cognitive
      impairment (MCI). Subjects with a CDRS score of 0 were classified as having aging
      associated cognitive decline (AACD). Serum BDNF levels were analyzed using the
      enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The serum BDNF levels
      were significantly lower in the subjects with MCI and AD compared with the
      healthy controls (p<0.01). A significant correlation was found between the total
      MMSE-KC score and serum BDNF level (r=0.295; p<0.01). However, no significant
      correlation was observed between the severity of MMSE-KC and the total GDS score.
      A significant difference was found in the total score of GDS between the AACD
      group and subjects with AD (p<0.05). CONCLUSION: This study suggested that BDNF
      might be involved in the pathophysiology of cognitive decline in elderly people.

PMID- 20140131
TI  - Resolution of pregabalin and mirtazapine associated restless legs syndrome by
      bupropion in a patient with major depressive disorder.
AB  - Bupropion is a selective norepinephrine and dopamine reuptake inhibitor with no
      serotonergic activity, and is therefore an antidepressant with unique
      pharmacological properties. There are some reports that selective serotonin
      reuptake inhibitors (SSRIs) or mirtazapine can induce adverse effects including
      restless legs syndrome (RLS) and that bupropion can reverse these adverse
      effects. Here, we report about a patient with a major depressive disorder who
      exhibited RLS after being treated with pregabalin and mirtazapine. This adverse
      effect disappeared after having switched from mirtazapine to bupropion. Bupropion
      inhibits the reuptake of dopamine and increases dopamine neurotransmission in
      both the nucleus accumbens and the prefrontal cortex. This pharmacological
      profile can be effective in patients with RLS related to dopamine hypoactivity.
      However, the limitations of this single case report mean that further
      investigations with larger samples are needed.

PMID- 20140130
TI  - Failure to detect borna disease virus antibody and RNA from peripheral blood
      mononuclear cells of psychiatric patients.
AB  - OBJECTIVE: Borna disease virus (BDV) is a highly neurotropic agent causing
      various neuropsychiatric symptoms in animals. Over the past two decades, it has
      been suggested that BDV might be associated with human psychiatric diseases. We
      aimed to investigate whether BDV is associated with psychiatric patients in
      Korea. METHODS: We recruited 60 normal controls and 198 psychiatric patients (98
      patients with depressive disorder, 60 with schizophrenia, and 40 with bipolar
      disorder). We used an indirect immunofluorescence antibody (IFA) test for the BDV
      antibody and a real-time reverse transcriptase polymerase chain reaction (rRT
      PCR) assay for p24 and p40 RNA from peripheral blood mononuclear cells (PBMCs).
      RESULTS: Neither the BDV antibody nor p24, p40 RNA was detected in controls and
      patients groups. CONCLUSION: Our results suggest that BDV might not be associated
      with psychiatric patients in Korea.

PMID- 20140132
TI  - Strategies to find candidate genes for bipolar disorder.

PMID- 20140134
TI  - What's in a Name?

PMID- 20140133
TI  - Mandatory vaccination of health care workers: whose rights should come first?

PMID- 20140135
TI  - An Interview Series with Members of the ASHP Expert Panel on Formulary
      Management: Part 1: Linda S. Tyler, PharmD.

PMID- 20140136
TI  - American society for bone and mineral research.

PMID- 20140137
TI  - Heparin revisions: a call for heightened vigilance and monitoring.

PMID- 20140138
TI  - Pharmaceutical approval update.

PMID- 20140139
TI  - A Human Monoclonal Antibody Against Tumor Necrosis Factor-alpha.

PMID- 20140140
TI  - An Interview Series with Members of the ASHP Expert Panel on Formulary
      Management: Part 2: J. Russell May, PharmD.

PMID- 20140141
TI  - Using Meta-analysis to Compare the Efficacy of Medications for Attention
      Deficit/Hyperactivity Disorder in Youths.
AB  - Medications used to treat attention-deficit/hyperactivity disorder (ADHD) have
      been well researched, but comparisons among agents are hindered by the absence of
      head-to-head clinical trials. By using meta-analysis, we sought to compare the
      efficacy of these medications for the symptoms of ADHD. We analyzed published
      literature on the pharmacotherapy of ADHD to describe the variability of drug
      placebo effect sizes and conducted a literature search to identify double-blind,
      placebo-controlled studies of youths with ADHD that were published after 1979.
      Meta-analysis regression was used to assess the influence of the medication type
      on drug effects. We also assessed for publication bias.Thirty-two trials met our
      criteria and were included in this meta-analysis. These trials involved 16 drugs
      using 20 different outcome measures of ADHD behaviors. The effect sizes for
      immediate-release stimulants and long-acting stimulants were similar and were
      greater than the effect sizes for non-stimulants. There was no evidence of
      publication bias.Although nearly all of the ADHD medications had significant
      effects, we found substantial variability. When translated into the costs of
      treating large numbers of patients, these effect sizes have implications for
      formulary medication choices.

PMID- 20140142
TI  - Comparative effectiveness research: valuable insight or government intrusion?

PMID- 20140143
TI  - Health Care Blog Watch: Pay-for-Delay and Authorized Generics Back in the
      Spotlight.

PMID- 20140145
TI  - Pharmaceutical approval update.

PMID- 20140144
TI  - American college of clinical pharmacy.

PMID- 20140146
TI  - Anatomical variations of the lumbar plexus: a descriptive anatomy study with
      proposed clinical implications.
AB  - This study used dissection of 34 lumbar plexes to look at the prevalence of
      anatomical variations in the lumbar plexus and the six peripheral branches from
      the origin at the ventral roots of (T12) L1-L4 to the exit from the pelvic
      cavity. Prevalence of anatomical variation in the individual nerves ranged from
      8.8-47.1% with a mean prevalence of 20.1%. Anatomical variations included absence
      of the iliohypogastric nerve, an early split of the genitofemoral nerve into
      genital and femoral branches, an aberrant segmental origin for the lateral
      femoral cutaneous nerve, bifurcation of the lateral femoral nerve prior to
      exiting the pelvic cavity, bifurcation of the femoral nerve into two to three
      slips separated by psoas major muscle fibers, the presence of a single anterior
      femoral cutaneous nerve rather than the normal presentation of two separate
      anterior femoral cutaneous branches, and the presence of an accessory obturator
      nerve. Comparison with relevant research literature showed a wide variation in
      reported prevalence of the anatomical variations noted in this study. Clinical
      implications and directions for future research are proposed.

PMID- 20140147
TI  - Re: "Interrater reliability of a new classification scheme for patients with
      neural low back-related leg pain" Schafer A et al. J Man Manip Ther 2009;17:109
      116.

PMID- 20140148
TI  - Author response.

PMID- 20140149
TI  - Continuity and change.

PMID- 20140150
TI  - An Exploration of Maitland's Concept of Pain Irritability in Patients with Low
      Back Pain.
AB  - Maitland's construct of musculoskeletal pain irritability is widely used by
      physical therapists for making decisions about the vigor of examination and
      treatment, but this construct has not been defined to the extent that its
      measurement properties can be tested. The purposes of this study were to 1)
      determine if physical therapists utilize low back pain (LBP) irritability
      judgments to make treatment decisions, 2) identify LBP characteristics
      appropriate for an LBP irritability construct, and 3) develop a measurement
      construct of LBP irritability. Physical therapists evaluated and treated 183
      subjects with LBP. The therapists judged the subjects' LBP as irritable or non
      irritable, and recorded treatments provided at the initial visit. A principal
      components analysis (PCA) was performed on 14 patient-reported LBP
      characteristics to identify potential components of a measurement construct of
      LBP irritability. The therapists' irritability judgments were found to be
      associated with the types of treatments prescribed. Five dimensions of LBP
      irritability were identified by the PCA from the 14 LBP characteristics
      considered. Four of these dimensions were associated with the therapists' LBP
      irritability judgments. The Roland-Morris Disability Questionnaire, presence of
      distal symptoms, and forward bending tolerance were found to have a stronger
      association with the irritability judgments than the dimensions of irritability
      identified in this study. Validated measures of LBP characteristics in current
      clinical use may adequately capture Maitland's concept of irritability.

PMID- 20140151
TI  - Effectiveness of manual physical therapy for painful shoulder conditions: a
      systematic review.
AB  - Multiple disease-specific systematic reviews on the effectiveness of physical
      therapy intervention for shoulder dysfunction have been inconclusive. To date,
      there have been two systematic reviews that examined manual therapy specifically
      but both considered effects within diagnoses. The purpose of this systematic
      review was to identify the effectiveness of manual therapy to the glenohumeral
      joint across all painful shoulder conditions. A search of MEDLINE, CINAHL, Web of
      Science, and Cochrane Central Register of Randomized Controlled Trials for
      articles dated 1996 to June 2009 was performed. Inclusion for review were manual
      therapy performed to the glenohumeral joint only; non-surgical painful shoulder
      disorders; subjects 18-80 years; and outcomes of range of motion, pain, function,
      and/or quality of life. Quality assessment was performed using the PEDro scale
      with subsequent data extraction. Seventeen related articles were found with seven
      fitting the inclusion criteria. The average PEDro score was 7.86, meeting the
      cutoff score for high quality. Significant heterogeneity in outcome measures
      prohibited meta-analysis. Five studies demonstrated benefits utilizing manual
      therapy for mobility, and four demonstrated a trend towards decreasing pain
      values. Functional outcomes and quality-of-life measures varied greatly among all
      studies. Manual therapy appears to increase either active or passive mobility of
      the shoulder. A trend was found favoring manual therapy for decreasing pain, but
      the effect on function and quality of life remains inconclusive. Future research
      utilizing consistent outcome measurements is necessary.

PMID- 20140152
TI  - A Case Study Examining the Effectiveness of Mechanical Diagnosis and Therapy in a
      Patient who Met the Clinical Prediction Rule for Spinal Manipulation.
AB  - This single-subject case study was conducted as a part of a randomized trial
      investigating the efficacy of mechanical diagnosis and therapy (MDT) and spinal
      thrust manipulation (STM) in patients who meet a clinical prediction rule (CPR)
      for spinal manipulation. Following initial examination, a patient who met the CPR
      was treated initially with STM and then eventually with MDT. The Oswestry
      Disability Questionnaire (ODI), Fear-Avoidance Beliefs Questionnaire, and the
      Numerical Pain Rating Scale (NPRS) were administered at the initial examination
      and at a two-week follow-up. Data were analyzed based on changes in the pain
      rating scale, ODI, and straight leg raise scores from initial examination to
      discharge. In accordance with a study protocol in which the patient was part of,
      this patient was changed from STM to MDT after the second physical therapy visit
      due to failure of overall improvement. The patient received MDT during the third
      session and continued with this approach until discharge. This patient responded
      favorably to MDT presenting with a 20 degrees improvement in SLR on the left and
      10 degrees on the right, 6 points lower on the NPRS, and a 4% decrease on the OSW
      after a total of 6 visits.

PMID- 20140153
TI  - Inter-tester Reliability in Classifying Acute and Subacute Low Back Pain Patients
      into Clinical Subgroups: A Comparison of Specialists and Non-Specialists. A Pilot
      Study.
AB  - Many systems have been suggested for classifying low back pain (LBP); the most
      commonly used among physiotherapists involves a
      pathoanatomical/pathophysiological tissue classification system. Few studies have
      examined whether this form of classification of LBP disorders can be performed in
      a reliable manner between specialists with advanced training, or between
      specialists with advanced training and non-specialists who lack advanced
      training. The purpose of this paper was to examine the inter-tester reliability
      of two specialists, and the ability of a specialist and non-specialist to
      independently classify patients with LBP, utilizing clinical tests and history
      based classification methods after a short educational course on the
      classification system. Subjects were acute or sub-acute patients with LBP who
      visited their occupational healthcare or municipal healthcare center. Inter
      tester reliability between the specialist and non-specialists was at almost the
      same level: overall Kappa 0.60 (95%CI; 0.40 to 0.85), overall agreement 70%, as
      between the two specialists: overall Kappa 0.65 (95%CI; 0.33-0.86), overall
      agreement 77%. The findings suggest that a short educational course can provide
      rather reliable examination tools to allow non-specialized physiotherapists to
      classify patients according to tissue origination.

PMID- 20140154
TI  - The immediate effects of thoracic spine and rib manipulation on subjects with
      primary complaints of shoulder pain.
AB  - Shoulder pain is a common orthopedic condition seen by physical therapists, with
      many potential contributing factors and proposed treatments. Although manual
      physical therapy interventions for the cervicothoracic spine and ribs have been
      investigated for this patient population, the specific effects of these
      treatments have not been reported. The purpose of this investigational study is
      to report the immediate effects of thoracic spine and rib manipulation in
      patients with primary complaints of shoulder pain. Using a test-retest design, 21
      subjects with shoulder pain were treated during a single treatment session with
      high-velocity thrust manipulation to the thoracic spine or upper ribs. Post
      treatment effects demonstrated a 51% (32mm) reduction in shoulder pain, a
      corresponding increase in shoulder range of motion (30 degrees -38 degrees ), and
      a mean patient-perceived global rating of change of 4.2 (median 5). These
      immediate post-treatment results suggest that thoracic and rib manipulative
      therapy is associated with improved shoulder pain and motion in patients with
      shoulder pain, and further these interventions support the concept of a regional
      interdependence between the thoracic spine, upper ribs, and shoulder.

PMID- 20140155
TI  - The effectiveness of thoracic spine manipulation for the management of
      musculoskeletal conditions: a systematic review and meta-analysis of randomized
      clinical trials.
AB  - Thoracic spine manipulation (TSM) is an intervention practiced by different
      professions, and recently an incursion of research using TSM has been published.
      The purpose of this review was to examine the effectiveness of TSM for the
      management of musculoskeletal conditions and the quality of trials that included
      TSM techniques. A comprehensive search of online databases was performed, and
      first authors of studies identified were contacted. Thirteen randomized clinical
      trials were included in the final review. The methodological quality of all
      studies was assessed using the 10-point PEDro scale. Seven of the 13 studies were
      of high quality. Three studies looked at TSM for treatment of shoulder
      conditions; however, there is limited evidence to support the use of TSM for
      shoulder conditions. Nine studies used TSM for the management of neck conditions.
      The meta-analysis identified a subset of homogeneous studies evaluating neck
      pain. The value of the pooled estimator (1.33) was statistically significant for
      the treatment effect of TSM in the studies with researcher effect removed (95 %
      confidence interval: 1.15, 1.52). This analysis suggests there is sufficient
      evidence to support the use of TSM for specific subgroups of patients with neck
      conditions. This review also identifies the need for further studies to examine
      the effectiveness of TSM to treat shoulder conditions and the effectiveness of
      TSM on neck conditions with long-term follow-up studies.

PMID- 20140156
TI  - Management and treatment of temporomandibular disorders: a clinical perspective.
AB  - A temporomandibular disorder (TMD) is a very common problem affecting up to 33%
      of individuals within their lifetime. TMD is often viewed as a repetitive motion
      disorder of the masticatory structures and has many similarities to
      musculoskeletal disorders of other parts of the body. Treatment often involves
      similar principles as other regions as well. However, patients with TMD and
      concurrent cervical pain exhibit a complex symptomatic behavior that is more
      challenging than isolated TMD symptoms. Although routinely managed by medical and
      dental practitioners, TMD may be more effectively cared for when physical
      therapists are involved in the treatment process. Hence, a listing of situations
      when practitioners should consider referring TMD patients to a physical therapist
      can be provided to the practitioners in each physical therapist's region. This
      paper should assist physical therapists with evaluating, treating, insurance
      billing, and obtaining referrals for TMD patients.

PMID- 20140158
TI  - Prolonged bone-conducted vibration in superior semicircular canal dehiscence and
      in otosclerosis: comparison of the 3D eye movement evaluation.
AB  - Vibration-induced nystagmus, as clinical sign, was recently introduced in
      outpatient clinical practice for the study and evaluation of otoneurological
      patients. This response, which can only be evoked by bone conducted vibratory
      stimulation in the mastoid region or at the location on the forehead in the
      midline at the hairline, was essentially designed for patients with persistent
      unilateral vestibular deficit and was interpreted as the result of excitatory
      functional activity of the vestibular system on the non-affected side. Vibratory
      stimulation is, in fact, considered to reach both systems, which in the case of
      functional asymmetry, respond asymmetrically with greater excitatory activation
      on the more responsive side. On the other hand, little information is available
      concerning vibration-induced nystagmus in subjects with symmetrical vestibular
      function. The limited experience with this recently proposed test and incomplete
      knowledge regarding its mechanisms suggest that it must be investigated in
      clinical conditions, having a known pathophysiological basis: the responses
      obtained could help provide insight into the potential of this test and
      contribute to the diagnostic definition of the superior semicircular canal
      dehiscence or otosclerosis. Analysis of Vibration-induced nystagmus, recently
      proposed to study transmission of excitatory stimuli by bone conduction, may be
      appropriate for altered input caused by defects of the labyrinthine capsule. This
      promises to be an interesting new field of research.

PMID- 20140157
TI  - Human Papilloma Virus (HPV) in head and neck region: review of literature.
AB  - The evidence that human papillomavirus infection is related to head and neck
      squamous cell carcinoma is supported by molecular and epidemiological data. The
      definition of a distinct subset of head and neck squamous cell carcinoma,
      independent of the traditional risk factors and with different clinical
      presentation and outcome, has led to increasing interest in human papillomavirus
      infection. This review summarizes current knowledge regarding human
      papillomavirus biology, oncogenic mechanisms, risk factors for transmission,
      clinical significance and prophylactic strategies.

PMID- 20140159
TI  - Nasal and lung function in competitive swimmers.
AB  - Nasal and sinusal complaints are considered common among swimmers. Aim of the
      present study was to evaluate the nasal and bronchial functions, before and after
      swimming, and the relationship between nasal resistances and FEV1 in competitive
      swimmers. A group of 30 competitive swimmers were examined: spirometry and nasal
      respiratory tests were carried out before and after swimming. Moreover, both the
      competitive swimmers and the 150 visitors of a swimming pool were asked to
      complete a specific questionnaire. In this questionnaire, 18% of the population
      reported nasal-sinusal symptoms after swimming. The differences between nasal
      volumes and resistances before and after swimming were not statistically
      significant. Nasal patency increased or remained unchanged in 21/30 athletes. The
      variations in FEV1 were not statistically significant. In conclusion, results
      showed that swimming is able to increase nasal patency or to leave it unchanged.
      Temporary worsening of the nasal patency was observed in only a few hyper
      reactive patients. In the whole group, no variations, at bronchial level, were
      found.

PMID- 20140160
TI  - Videokymographic analysis of patients after frontolateral laryngectomy with
      sternohyoid muscle flap reconstruction.
AB  - A retrospective study was conducted to analyse videokymographic findings from
      patients who underwent vertical frontolateral laryngectomy with reconstruction
      using a sternohyoid muscle flap. Overall, 22 patients with T1b and T2 glottic
      tumours and more than one year of follow-up were studied. Two experienced
      observers analysed the recorded videokymographic data. A cross-sectional
      descriptive design was used. The images showed the vocal vibratory behaviour
      during sustained /i/ phonation. The vibratory source was supraglottic in 7/22
      patients, glottic in 11 and mixed in 4. The mean duration of the glottic cycles
      extracted from the supraglottic, mixed and glottic vibratory sources was 6.4 ms,
      5 ms and 4.6 ms, corresponding to the fundamental frequency (f0) of 188.7 Hz, 200
      Hz and 215.7 Hz, respectively. Of the 11 patients with a glottic vibratory
      source, 4 did not present a closed phase in the glottic cycle. The mean open
      quotient was 79%, 40% and 63%, for the supraglottic, mixed and glottic vibratory
      sources, respectively. All 11 reconstructed vocal cords presented a rounded
      lateral peak. Of the 15 preserved vocal cords, 11 presented a rounded lateral
      peak and 4 had sharp peaks. All patients with a glottic vibratory source
      presented a rounded medial peak. All the vocal cords evaluated presented a
      mucosal wave, which was normal in 3 patients with a glottic source and clearly
      reduced in the others. Only one case presented phase asymmetry. The mean values
      for the amplitude asymmetry index were 0.92 and 0.68, for the mixed and
      supraglottic vibratory sources, respectively.

PMID- 20140161
TI  - Complications of using laryngeal mask airway during anaesthesia in patients
      undergoing major ear surgery.
AB  - Use of the laryngoscope and tracheal tube during general anaesthesia results in
      many complications such as sore throat, cough, vocal cord paralysis, compulsory
      injection of muscle relaxants for tube insertion and risky emergence of
      anaesthesia. This study investigated the use of laryngeal mask airway (LMA) as a
      safe and complication-free device in patients undergoing ear surgery. This is a
      retrospective cross-sectional study on a population comprising patients from 3 to
      70 years of age who have undergone major ear surgery, in Amir Alam Hospital, from
      1999 to 2006. Laryngeal mask airway replaced the tracheal tube in all patients.
      Of the 2000 patients who underwent major ear surgery with general anaesthesia
      using LMA, 246 (12.3%) developed haemodynamic instability. A significant
      relationship was observed between age and haemodynamic instability (p value =
      0.03); 14.9% of these patients were aged between 16 and 40 years and 20% were
      aged > 60 years. No relationship was observed between the occurrence of this
      complication and duration of surgery (p value = 0.2). Furthermore, no significant
      relationship was observed between sex and haemodynamic instability. In
      conclusion, considering the low rate of complications with laryngeal mask airway,
      replacing tracheal tube with this device in major ear surgery will lead to a
      noticeable decrease in associated complications.

PMID- 20140162
TI  - Salivary glands: report of a rare case of myoepithelial carcinoma involving
      tongue base treated by CO2 Laser.
AB  - Epithelial-myoepithelial carcinoma is a rare malignant tumour of the salivary
      glands. Herewith, the clinical evolution, anatomo-pathological characteristics
      and treatment adopted are described in a case occurring in the minor salivary
      glands of the tongue base. To our knowledge, this location has not been
      previously described in the literature. In fact, due to the rarity of the
      epithelial-myoepithelial carcinoma, there is no uniformity of data in the
      literature and very different therapeutic strategies have been suggested. In this
      report, the possibility of applying conservative surgery using CO(2) Laser is
      proposed. Results obtained in the case described confirm that conservative
      surgery is feasible in this type of neoplastic lesion of the tongue.

PMID- 20140163
TI  - Necrotizing fasciitis of the neck associated with Lemierre syndrome.
AB  - Necrotizing fasciitis of the head and neck is a rare, life-threatening, soft
      tissue infection rapidly involving superficial fat and fascia with necrosis of
      the overlying skin. If septic thrombophlebitis of the internal jugular vein
      complicates a parapharyngeal abscess, the clinical condition is referred to as
      Lemierre syndrome, also known as post-anginal sepsis. A lethal case of
      necrotizing fasciitis of the neck is herewith reported that developed following
      tooth extraction and was complicated by thrombosis of the internal jugular vein
      and superior vena cava in an elderly diabetic patient.

PMID- 20140165
TI  - Gradenigo's syndrome and Dorello's canal.

PMID- 20140164
TI  - Esthesioneuroblastoma metastatic to the trachea.
AB  - Esthesioneuroblastoma is a rare tumour, for which a multimodal approach,
      including a combination of surgery and radiation, appears to provide the best
      disease-free and overall survival. Well-known for its tendency for local
      recurrence and distant spreading by both lymphatic and haematogenous routes, the
      most common sites of metastases are lungs and bones, followed by liver, spleen,
      scalp, breast, adrenals and ovary. One single case of metastasis to the trachea
      has been reported in the literature. The case is reported here of a patient who
      developed metastatic esthesioneuroblastoma to the trachea 18 months after primary
      surgery and radiation therapy. The patient was treated by two subsequent N-YAG
      laser endoscopic resections and chemotherapy.

PMID- 20140169
TI  - eCAM: Proteomics, BioArt and Integrative Medicine?

PMID- 20140170
TI  - Identification of adverse drug events: the use of ICD-10 coded diagnoses in
      routine hospital data.
AB  - BACKGROUND: Adverse drug events (ADE) are a common cause of hospital admission as
      well as a common complication of inpatient care. The current reporting systems in
      Germany are of only limited use for the identification of ADE. The aim of this
      study is to examine the potential usefulness of ICD-10 coded diagnoses in routine
      hospital data for the identification of ADE. METHODS: The common, major
      manifestations of ADE were mapped to the ICD-10-GM, and categories in the ICD-10
      GM for which a possible causal relationship with medications is explicitly
      mentioned were included as well. A total of 505 relevant ICD-10-GM codes were
      identified. An evaluation was carried out on the basis of an aggregated data set
      from eleven million inpatients treated in 2006. RESULTS: 0.7% of hospital
      admissions were revealed by routine data to be causally related to the
      administration of a drug. In 5.3% of admissions, there was at least a reason to
      suspect such a causal relation. Furthermore, one of the 505 relevant codes was
      found to be present in 9.0% of the secondary diagnoses. CONCLUSIONS: The
      available ICD-10-GM codes for manifestations of ADE are used in routine hospital
      data in Germany. Their usefulness for the identification of ADE should be better
      exploited. Our results and other relevant published literature imply that this
      procedure will result in both false-positive and false-negative findings, which
      will have to be taken into account as well.

PMID- 20140171
TI  - Follow-up endoscopy in gastroenterology: when is it helpful?
AB  - BACKGROUND: The indications for follow-up endoscopy have not been established in
      all diseases that can be diagnosed by endoscopy. METHODS: Selective review of the
      literature and a survey of national guidelines. RESULTS: In confirmed erosive or
      non-erosive reflux disease, follow-up endoscopy is indicated only in the presence
      of complications or Barrett's esophagus. In the case of gastric ulcer or
      complicated duodenal ulcer, monitoring by endoscopy is mandatory. There is no
      consensus regarding the indication for follow-up biopsy in confirmed endemic
      sprue. In an acute episode of confirmed ulcerative colitis, endoscopy is
      indicated only if the treatment depends on the findings. In confirmed Crohn's
      disease, this procedure is indicated only in the presence of complications, if
      the findings are unclear, and before elective intestinal surgery. Those at risk
      of hereditary colorectal carcinoma without polyposis should undergo colonoscopy
      annually, starting 5 years before the youngest age of occurrence in their family
      or at the age of 25 years, whichever comes first. CONCLUSIONS: With particular
      reference to further gastrointestinal diseases discussed in the main text, this
      review unfortunately shows that many of the indications for follow-up endoscopy
      remain to be ascertained. Controlled studies are needed to establish with
      sufficient certainty what really helps our patients.

PMID- 20140172
TI  - How up to date was this information?

PMID- 20140173
TI  - Recommended fluid intake should be tailored to the individual.

PMID- 20140174
TI  - Psychosocial aftercare after organ transplantation.

PMID- 20140176
TI  - Correction required.

PMID- 20140177
TI  - Clinical relevance.

PMID- 20140178
TI  - Bacteriological stool examinations.

PMID- 20140181
TI  - Course and pathogenesis.

PMID- 20140182
TI  - In silico analysis of the apolipoprotein E and the amyloid beta peptide
      interaction: misfolding induced by frustration of the salt bridge network.
AB  - The relationship between Apolipoprotein E (ApoE) and the aggregation processes of
      the amyloid beta (A beta) peptide has been shown to be crucial for Alzheimer's
      disease (AD). The presence of the ApoE4 isoform is considered to be a
      contributing risk factor for AD. However, the detailed molecular properties of
      ApoE4 interacting with the A beta peptide are unknown, although various
      mechanisms have been proposed to explain the physiological and pathological role
      of this relationship. Here, computer simulations have been used to investigate
      the process of A beta interaction with the N-terminal domain of the human ApoE
      isoforms (ApoE2, ApoE3 and ApoE4). Molecular docking combined with molecular
      dynamics simulations have been undertaken to determine the A beta peptide binding
      sites and the relative stability of binding to each of the ApoE isoforms. Our
      results show that from the several ApoE isoforms investigated, only ApoE4
      presents a misfolded intermediate when bound to A beta. Moreover, the initial
      alpha-helix used as the A beta peptide model structure also becomes unstructured
      due to the interaction with ApoE4. These structural changes appear to be related
      to a rearrangement of the salt bridge network in ApoE4, for which we propose a
      model. It seems plausible that ApoE4 in its partially unfolded state is incapable
      of performing the clearance of A beta, thereby promoting amyloid forming
      processes. Hence, the proposed model can be used to identify potential drug
      binding sites in the ApoE4-A beta complex, where the interaction between the two
      molecules can be inhibited.

PMID- 20140184
TI  - Distinct external signals trigger sequential release of apical organelles during
      erythrocyte invasion by malaria parasites.
AB  - The invasion of erythrocytes by Plasmodium merozoites requires specific
      interactions between host receptors and parasite ligands. Parasite proteins that
      bind erythrocyte receptors during invasion are localized in apical organelles
      called micronemes and rhoptries. The regulated secretion of microneme and rhoptry
      proteins to the merozoite surface to enable receptor binding is a critical step
      in the invasion process. The sequence of these secretion events and the external
      signals that trigger release are not known. We have used time-lapse video
      microscopy to study changes in intracellular calcium levels in Plasmodium
      falciparum merozoites during erythrocyte invasion. In addition, we have developed
      flow cytometry based methods to measure relative levels of cytosolic calcium and
      study surface expression of apical organelle proteins in P. falciparum merozoites
      in response to different external signals. We demonstrate that exposure of P.
      falciparum merozoites to low potassium ion concentrations as found in blood
      plasma leads to a rise in cytosolic calcium levels through a phospholipase C
      mediated pathway. Rise in cytosolic calcium triggers secretion of microneme
      proteins such as the 175 kD erythrocyte binding antigen (EBA175) and apical
      membrane antigen-1 (AMA-1) to the merozoite surface. Subsequently, interaction of
      EBA175 with glycophorin A (glyA), its receptor on erythrocytes, restores basal
      cytosolic calcium levels and triggers release of rhoptry proteins. Our results
      identify for the first time the external signals responsible for the sequential
      release of microneme and rhoptry proteins during erythrocyte invasion and provide
      a starting point for the dissection of signal transduction pathways involved in
      regulated exocytosis of these key apical organelles. Signaling pathway components
      involved in apical organelle discharge may serve as novel targets for drug
      development since inhibition of microneme and rhoptry secretion can block
      invasion and limit blood-stage parasite growth.

PMID- 20140183
TI  - Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular
      degeneration.
AB  - A common haplotype on 10q26 influences the risk of age-related macular
      degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data
      have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del)
      that destabilizes its message, is causally related with the disorder. Here we
      show that loss of LOC387715 is insufficient to explain AMD susceptibility, since
      a nonsense mutation (R38X) in this gene that leads to loss of its message resides
      in a protective haplotype. At the same time, the common disease haplotype tagged
      by the in/del and rs11200638 has an effect on the transcriptional upregulation of
      the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the
      pathogenesis of AMD and highlight the importance of exploring multiple functional
      consequences of alleles in haplotypes that confer susceptibility to complex
      traits.

PMID- 20140185
TI  - Replication and active demethylation represent partially overlapping mechanisms
      for erasure of H3K4me3 in budding yeast.
AB  - Histone modifications affect DNA-templated processes ranging from transcription
      to genomic replication. In this study, we examine the cell cycle dynamics of the
      trimethylated form of histone H3 lysine 4 (H3K4me3), a mark of active chromatin
      that is viewed as "long-lived" and that is involved in memory during cell state
      inheritance in metazoans. We synchronized yeast using two different protocols,
      then followed H3K4me3 patterns as yeast passed through subsequent cell cycles.
      While most H3K4me3 patterns were conserved from one generation to the next, we
      found that methylation patterns induced by alpha factor or high temperature were
      erased within one cell cycle, during S phase. Early-replicating regions were
      erased before late-replicating regions, implicating replication in H3K4me3 loss.
      However, nearly complete H3K4me3 erasure occurred at the majority of loci even
      when replication was prevented, suggesting that most erasure results from an
      active process. Indeed, deletion of the demethylase Jhd2 slowed erasure at most
      loci. Together, these results indicate overlapping roles for passive dilution and
      active enzymatic demethylation in erasing ancestral histone methylation states in
      yeast.

PMID- 20140186
TI  - Explicit kinetic heterogeneity: mathematical models for interpretation of
      deuterium labeling of heterogeneous cell populations.
AB  - Estimation of division and death rates of lymphocytes in different conditions is
      vital for quantitative understanding of the immune system. Deuterium, in the form
      of deuterated glucose or heavy water, can be used to measure rates of
      proliferation and death of lymphocytes in vivo. Inferring these rates from
      labeling and delabeling curves has been subject to considerable debate with
      different groups suggesting different mathematical models for that purpose. We
      show that the three most common models, which are based on quite different
      biological assumptions, actually predict mathematically identical labeling curves
      with one parameter for the exponential up and down slope, and one parameter
      defining the maximum labeling level. By extending these previous models, we here
      propose a novel approach for the analysis of data from deuterium labeling
      experiments. We construct a model of "kinetic heterogeneity" in which the total
      cell population consists of many sub-populations with different rates of cell
      turnover. In this model, for a given distribution of the rates of turnover, the
      predicted fraction of labeled DNA accumulated and lost can be calculated. Our
      model reproduces several previously made experimental observations, such as a
      negative correlation between the length of the labeling period and the rate at
      which labeled DNA is lost after label cessation. We demonstrate the reliability
      of the new explicit kinetic heterogeneity model by applying it to artificially
      generated datasets, and illustrate its usefulness by fitting experimental data.
      In contrast to previous models, the explicit kinetic heterogeneity model 1)
      provides a novel way of interpreting labeling data; 2) allows for a non
      exponential loss of labeled cells during delabeling, and 3) can be used to
      describe data with variable labeling length.

PMID- 20140187
TI  - Deletion of the huntingtin polyglutamine stretch enhances neuronal autophagy and
      longevity in mice.
AB  - Expansion of a stretch of polyglutamine in huntingtin (htt), the protein product
      of the IT15 gene, causes Huntington's disease (HD). Previous investigations into
      the role of the polyglutamine stretch (polyQ) in htt function have suggested that
      its length may modulate a normal htt function involved in regulating energy
      homeostasis. Here we show that expression of full-length htt lacking its
      polyglutamine stretch (DeltaQ-htt) in a knockin mouse model for HD
      (Hdh(140Q/DeltaQ)), reduces significantly neuropil mutant htt aggregates,
      ameliorates motor/behavioral deficits, and extends lifespan in comparison to the
      HD model mice (Hdh(140Q/+)). The rescue of HD model phenotypes is accompanied by
      the normalization of lipofuscin levels in the brain and an increase in the steady
      state levels of the mammalian autophagy marker microtubule-associate protein 1
      light chain 3-II (LC3-II). We also find that DeltaQ-htt expression in vitro
      increases autophagosome synthesis and stimulates the Atg5-dependent clearance of
      truncated N-terminal htt aggregates. DeltaQ-htt's effect on autophagy most likely
      represents a gain-of-function, as overexpression of full-length wild-type htt in
      vitro does not increase autophagosome synthesis. Moreover, Hdh(DeltaQ/DeltaQ)
      mice live significantly longer than wild-type mice, suggesting that autophagy
      upregulation may be beneficial both in diseases caused by toxic intracellular
      aggregate-prone proteins and also as a lifespan extender in normal mammals.

PMID- 20140188
TI  - Genomic hotspots for adaptation: the population genetics of Mullerian mimicry in
      the Heliconius melpomene clade.
AB  - Wing patterning in Heliconius butterflies is a longstanding example of both
      Mullerian mimicry and phenotypic radiation under strong natural selection. The
      loci controlling such patterns are "hotspots" for adaptive evolution with great
      allelic diversity across different species in the genus. We characterise
      nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium,
      and candidate gene expression at two loci and across multiple hybrid zones in
      Heliconius melpomene and relatives. Alleles at HmB control the presence or
      absence of the red forewing band, while alleles at HmYb control the yellow
      hindwing bar. Across HmYb two regions, separated by approximately 100 kb, show
      significant genotype-by-phenotype associations that are replicated across
      independent hybrid zones. In contrast, at HmB a single peak of association
      indicates the likely position of functional sites at three genes, encoding a
      kinesin, a G-protein coupled receptor, and an mRNA splicing factor. At both HmYb
      and HmB there is evidence for enhanced linkage disequilibrium (LD) between
      associated sites separated by up to 14 kb, suggesting that multiple sites are
      under selection. However, there was no evidence for reduced variation or
      deviations from neutrality that might indicate a recent selective sweep,
      consistent with these alleles being relatively old. Of the three genes showing an
      association with the HmB locus, the kinesin shows differences in wing disc
      expression between races that are replicated in the co-mimic, Heliconius erato,
      providing striking evidence for parallel changes in gene expression between
      Mullerian co-mimics. Wing patterning loci in Heliconius melpomene therefore show
      a haplotype structure maintained by selection, but no evidence for a recent
      selective sweep. The complex genetic pattern contrasts with the simple genetic
      basis of many adaptive traits studied previously, but may provide a better model
      for most adaptation in natural populations that has arisen over millions rather
      than tens of years.

PMID- 20140189
TI  - The overlap of small molecule and protein binding sites within families of
      protein structures.
AB  - Protein-protein interactions are challenging targets for modulation by small
      molecules. Here, we propose an approach that harnesses the increasing structural
      coverage of protein complexes to identify small molecules that may target protein
      interactions. Specifically, we identify ligand and protein binding sites that
      overlap upon alignment of homologous proteins. Of the 2,619 protein structure
      families observed to bind proteins, 1,028 also bind small molecules (250-1000
      Da), and 197 exhibit a statistically significant (p<0.01) overlap between ligand
      and protein binding positions. These "bi-functional positions", which bind both
      ligands and proteins, are particularly enriched in tyrosine and tryptophan
      residues, similar to "energetic hotspots" described previously, and are
      significantly less conserved than mono-functional and solvent exposed positions.
      Homology transfer identifies ligands whose binding sites overlap at least 20% of
      the protein interface for 35% of domain-domain and 45% of domain-peptide mediated
      interactions. The analysis recovered known small-molecule modulators of protein
      interactions as well as predicted new interaction targets based on the sequence
      similarity of ligand binding sites. We illustrate the predictive utility of the
      method by suggesting structural mechanisms for the effects of sanglifehrin A on
      HIV virion production, bepridil on the cellular entry of anthrax edema factor,
      and fusicoccin on vertebrate developmental pathways. The results, available at
      http://pibase.janelia.org, represent a comprehensive collection of structurally
      characterized modulators of protein interactions, and suggest that homologous
      structures are a useful resource for the rational design of interaction
      modulators.

PMID- 20140190
TI  - A kinase-independent role for the Rad3(ATR)-Rad26(ATRIP) complex in recruitment
      of Tel1(ATM) to telomeres in fission yeast.
AB  - ATM and ATR are two redundant checkpoint kinases essential for the stable
      maintenance of telomeres in eukaryotes. Previous studies have established that
      MRN (Mre11-Rad50-Nbs1) and ATRIP (ATR Interacting Protein) interact with ATM and
      ATR, respectively, and recruit their partner kinases to sites of DNA damage.
      Here, we investigated how Tel1(ATM) and Rad3(ATR) recruitment to telomeres is
      regulated in fission yeast. Quantitative chromatin immunoprecipitation (ChIP)
      assays unexpectedly revealed that the MRN complex could also contribute to the
      recruitment of Tel1(ATM) to telomeres independently of the previously established
      Nbs1 C-terminal Tel1(ATM) interaction domain. Recruitment of Tel1(ATM) to
      telomeres in nbs1-c60Delta cells, which lack the C-terminal 60 amino acid
      Tel1(ATM) interaction domain of Nbs1, was dependent on Rad3(ATR)-Rad26(ATRIP),
      but the kinase domain of Rad3(ATR) was dispensable. Thus, our results establish
      that the Rad3(ATR)-Rad26(ATRIP) complex contributes to the recruitment of
      Tel1(ATM) independently of Rad3(ATR) kinase activity, by a mechanism redundant
      with the Tel1(ATM) interaction domain of Nbs1. Furthermore, we found that the N
      terminus of Nbs1 contributes to the recruitment of Rad3(ATR)-Rad26(ATRIP) to
      telomeres. In response to replication stress, mammalian ATR-ATRIP also
      contributes to ATM activation by a mechanism that is dependent on the MRN complex
      but independent of the C-terminal ATM interaction domain of Nbs1. Since telomere
      protection and DNA damage response mechanisms are very well conserved between
      fission yeast and mammalian cells, mammalian ATR-ATRIP may also contribute to the
      recruitment of ATM to telomeres and to sites of DNA damage independently of ATR
      kinase activity.

PMID- 20140191
TI  - A variant of TNFR2-Fc fusion protein exhibits improved efficacy in treating
      experimental rheumatoid arthritis.
AB  - Etanercept, a TNF receptor 2-Fc fusion protein, is currently being used for the
      treatment of rheumatoid arthritis (RA). However, 25% to 38% of patients show no
      response which is suspected to be partially due to insufficient affinity of this
      protein to TNFalpha. By using computational protein design, we found that residue
      W89 and E92 of TNFR2 were critical for ligand binding. Among several mutants
      tested, W89Y/E92N displayed 1.49-fold higher neutralizing activity to TNFalpha,
      as compared to that of Etanercept. Surface plasmon resonance (SPR) based binding
      assay revealed that the equilibrium dissociation constant of W89Y/E92N to
      TNFalpha was 3.65-fold higher than that of Etanercept. In a rat model of collagen
      induced arthritis (CIA), W89Y/E92N showed a significantly better ability than
      Etanercept in reducing paw swelling and improvement of arthritic joint
      histopathologically. These data demonstrate that W89Y/E92N is potentially a
      better candidate with improved efficacy in treating RA and other autoimmune
      diseases.

PMID- 20140192
TI  - Immunoelectron microscopic evidence for Tetherin/BST2 as the physical bridge
      between HIV-1 virions and the plasma membrane.
AB  - Tetherin/BST2 was identified in 2008 as the cellular factor responsible for
      restricting HIV-1 replication at a very late stage in the lifecycle. Tetherin
      acts to retain virion particles on the plasma membrane after budding has been
      completed. Infected cells that express large amounts of tetherin display large
      strings of HIV virions that remain attached to the plasma membrane. Vpu is an HIV
      1 accessory protein that specifically counteracts the restriction to virus
      release contributed by tetherin. Tetherin is an unusual Type II transmembrane
      protein that contains a GPI anchor at its C-terminus and is found in lipid rafts.
      The leading model for the mechanism of action of tetherin is that it functions as
      a direct physical tether bridging virions and the plasma membrane. However,
      evidence that tetherin functions as a physical tether has thus far been indirect.
      Here we demonstrate by biochemical and immunoelectron microscopic methods that
      endogenous tetherin is present on the viral particle and forms a bridge between
      virion particles and the plasma membrane. Endogenous tetherin was found on HIV
      particles that were released by partial proteolytic digestion. Immunoelectron
      microscopy performed on HIV-infected T cells demonstrated that tetherin forms an
      apparent physical link between virions and connects patches of virions to the
      plasma membrane. Linear filamentous strands that were highly enriched in tetherin
      bridged the space between some virions. We conclude that tetherin is the physical
      tether linking HIV-1 virions and the plasma membrane. The presence of filaments
      with which multiple molecules of tetherin interact in connecting virion particles
      is strongly suggested by the morphologic evidence.

PMID- 20140193
TI  - Structural and biochemical characterization of SrcA, a multi-cargo type III
      secretion chaperone in Salmonella required for pathogenic association with a
      host.
AB  - Many Gram-negative bacteria colonize and exploit host niches using a protein
      apparatus called a type III secretion system (T3SS) that translocates bacterial
      effector proteins into host cells where their functions are essential for
      pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the
      bacterial cytosol, establishing protein interaction networks needed for effector
      translocation into host cells. In Salmonella enterica serovar Typhimurium, a T3SS
      encoded in a large genomic island (SPI-2) is required for intracellular
      infection, but the chaperone complement required for effector translocation by
      this system is not known. Using a reverse genetics approach, we identified a
      multi-cargo secretion chaperone that is functionally integrated with the SPI-2
      encoded T3SS and required for systemic infection in mice. Crystallographic
      analysis of SrcA at a resolution of 2.5 A revealed a dimer similar to the CesT
      chaperone from enteropathogenic E. coli but lacking a 17-amino acid extension at
      the carboxyl terminus. Further biochemical and quantitative proteomics data
      revealed three protein interactions with SrcA, including two effector cargos
      (SseL and PipB2) and the type III-associated ATPase, SsaN, that increases the
      efficiency of effector translocation. Using competitive infections in mice we
      show that SrcA increases bacterial fitness during host infection, highlighting
      the in vivo importance of effector chaperones for the SPI-2 T3SS.

PMID- 20140194
TI  - An extensive circuitry for cell wall regulation in Candida albicans.
AB  - Protein kinases play key roles in signaling and response to changes in the
      external environment. The ability of Candida albicans to quickly sense and
      respond to changes in its environment is key to its survival in the human host.
      Our guiding hypothesis was that creating and screening a set of protein kinase
      mutant strains would reveal signaling pathways that mediate stress response in C.
      albicans. A library of protein kinase mutant strains was created and screened for
      sensitivity to a variety of stresses. For the majority of stresses tested, stress
      response was largely conserved between C. albicans, Saccharomyces cerevisiae, and
      Schizosaccharomyces pombe. However, we identified eight protein kinases whose
      roles in cell wall regulation (CWR) were not expected from functions of their
      orthologs in the model fungi Saccharomyces cerevisiae and Schizosaccharomyces
      pombe. Analysis of the conserved roles of these protein kinases indicates that
      establishment of cell polarity is critical for CWR. In addition, we found that
      septins, crucial to budding, are both important for surviving and are
      mislocalized by cell wall stress. Our study shows an expanded role for protein
      kinase signaling in C. albicans cell wall integrity. Our studies suggest that in
      some cases, this expansion represents a greater importance for certain pathways
      in cell wall biogenesis. In other cases, it appears that signaling pathways have
      been rewired for a cell wall integrity response.

PMID- 20140195
TI  - TgMORN1 is a key organizer for the basal complex of Toxoplasma gondii.
AB  - Toxoplasma gondii is a leading cause of congenital birth defects, as well as a
      cause for ocular and neurological diseases in humans. Its cytoskeleton is
      essential for parasite replication and invasion and contains many unique
      structures that are potential drug targets. Therefore, the biogenesis of the
      cytoskeletal structure of T. gondii is not only important for its pathogenesis,
      but also of interest to cell biology in general. Previously, we and others
      identified a new T. gondii cytoskeletal protein, TgMORN1, which is recruited to
      the basal complex at the very beginning of daughter formation. However, its
      function remained largely unknown. In this study, we generated a knock-out mutant
      of TgMORN1 (DeltaTgMORN1) using a Cre-LoxP based approach. We found that the
      structure of the basal complex was grossly affected in DeltaTgMORN1 parasites,
      which also displayed defects in cytokinesis. Moreover, DeltaTgMORN1 parasites
      showed significant growth impairment in vitro, and this translated into greatly
      attenuated virulence in mice. Therefore, our results demonstrate that TgMORN1 is
      required for maintaining the structural integrity of the parasite posterior end,
      and provide direct evidence that cytoskeleton integrity is essential for parasite
      virulence and pathogenesis.

PMID- 20140197
TI  - Neutrophil-derived CCL3 is essential for the rapid recruitment of dendritic cells
      to the site of Leishmania major inoculation in resistant mice.
AB  - Neutrophils are rapidly and massively recruited to sites of microbial infection,
      where they can influence the recruitment of dendritic cells. Here, we have
      analyzed the role of neutrophil released chemokines in the early recruitment of
      dendritic cells (DCs) in an experimental model of Leishmania major infection. We
      show in vitro, as well as during infection, that the parasite induced the
      expression of CCL3 selectively in neutrophils from L. major resistant mice.
      Neutrophil-secreted CCL3 was critical in chemotaxis of immature DCs, an effect
      lost upon CCL3 neutralisation. Depletion of neutrophils prior to infection, as
      well as pharmacological or genetic inhibition of CCL3, resulted in a significant
      decrease in DC recruitment at the site of parasite inoculation. Decreased DC
      recruitment in CCL3(-/-) mice was corrected by the transfer of wild type
      neutrophils at the time of infection. The early release of CCL3 by neutrophils
      was further shown to have a transient impact on the development of a protective
      immune response. Altogether, we identified a novel role for neutrophil-secreted
      CCL3 in the first wave of DC recruitment to the site of infection with L. major,
      suggesting that the selective release of neutrophil-secreted chemokines may
      regulate the development of immune response to pathogens.

PMID- 20140196
TI  - Reverse genetics in Candida albicans predicts ARF cycling is essential for drug
      resistance and virulence.
AB  - Candida albicans, the major fungal pathogen of humans, causes life-threatening
      infections in immunocompromised individuals. Due to limited available therapy
      options, this can frequently lead to therapy failure and emergence of drug
      resistance. To improve current treatment strategies, we have combined
      comprehensive chemical-genomic screening in Saccharomyces cerevisiae and
      validation in C. albicans with the goal of identifying compounds that can couple
      with the fungistatic drug fluconazole to make it fungicidal. Among the genes
      identified in the yeast screen, we found that only AGE3, which codes for an ADP
      ribosylation factor GTPase activating effector protein, abrogates fluconazole
      tolerance in C. albicans. The age3 mutant was more sensitive to other sterols and
      cell wall inhibitors, including caspofungin. The deletion of AGE3 in drug
      resistant clinical isolates and in constitutively active calcineurin signaling
      mutants restored fluconazole sensitivity. We confirmed chemically the AGE3
      dependent drug sensitivity by showing a potent fungicidal synergy between
      fluconazole and brefeldin A (an inhibitor of the guanine nucleotide exchange
      factor for ADP ribosylation factors) in wild type C. albicans as well as in drug
      resistant clinical isolates. Addition of calcineurin inhibitors to the
      fluconazole/brefeldin A combination only initially improved pathogen killing.
      Brefeldin A synergized with different drugs in non-albicans Candida species as
      well as Aspergillus fumigatus. Microarray studies showed that core
      transcriptional responses to two different drug classes are not significantly
      altered in age3 mutants. The therapeutic potential of inhibiting ARF activities
      was demonstrated by in vivo studies that showed age3 mutants are avirulent in
      wild type mice, attenuated in virulence in immunocompromised mice and that
      fluconazole treatment was significantly more efficacious when ARF signaling was
      genetically compromised. This work describes a new, widely conserved, broad
      spectrum mechanism involved in fungal drug resistance and virulence and offers a
      potential route for single or improved combination therapies.

PMID- 20140198
TI  - Exacerbated innate host response to SARS-CoV in aged non-human primates.
AB  - The emergence of viral respiratory pathogens with pandemic potential, such as
      severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1,
      urges the need for deciphering their pathogenesis to develop new intervention
      strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop
      into life-threatening acute respiratory distress syndrome (ARDS) with advanced
      age correlating positively with adverse disease outcome. The molecular pathways,
      however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined.
      Here, we show that SARS-CoV-infected aged macaques develop more severe pathology
      than young adult animals, even though viral replication levels are similar.
      Comprehensive genomic analyses indicate that aged macaques have a stronger host
      response to virus infection than young adult macaques, with an increase in
      differential expression of genes associated with inflammation, with NF-kappaB as
      central player, whereas expression of type I interferon (IFN)-beta is reduced.
      Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces
      pathology and diminishes pro-inflammatory gene expression, including interleukin
      8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in
      SARS-CoV-infected aged macaques developed as a result of an exacerbated innate
      host response. The anti-inflammatory action of type I IFN reveals a potential
      intervention strategy for virus-induced ALI.

PMID- 20140200
TI  - Perturbation of the P-body component Mov10 inhibits HIV-1 infectivity.
AB  - Exogenous retroviruses are obligate cellular parasites that co-opt a number of
      host proteins and functions to enable their replication and spread. Several host
      factors that restrict HIV and other retroviral infections have also recently been
      described. Here we demonstrate that Mov10, a protein associated with P-bodies
      that has a putative RNA-helicase domain, when overexpressed in cells can inhibit
      the production of infectious retroviruses. Interestingly, reducing the endogenous
      Mov10 levels in virus-producing cells through siRNA treatment also modestly
      suppresses HIV infectivity. The actions of Mov10 are not limited to HIV, however,
      as ectopic expression of Mov10 restricts the production of other lentiviruses as
      well as the gammaretrovirus, murine leukemia virus. We found that HIV produced in
      the presence of high levels of Mov10 is restricted at the pre-reverse
      transcription stage in target cells. Finally, we show that either helicase
      mutation or truncation of the C-terminal half of Mov10, where a putative RNA
      helicase domain is located, maintained most of its HIV inhibition; whereas
      removing the N-terminal half of Mov10 completely abolished its activity on HIV.
      Together these results suggest that Mov10 could be required during the lentiviral
      lifecycle and that its perturbation disrupts generation of infectious viral
      particles. Because Mov10 is implicated as part of the P-body complex, these
      findings point to the potential role of cytoplasmic RNA processing machinery in
      infectious retroviral production.

PMID- 20140199
TI  - IPS-1 is essential for the control of West Nile virus infection and immunity.
AB  - The innate immune response is essential for controlling West Nile virus (WNV)
      infection but how this response is propagated and regulates adaptive immunity in
      vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to
      RIG-I-like receptor (RLR) signaling, is essential for triggering of innate
      immunity and for effective development and regulation of adaptive immunity
      against pathogenic WNV. IPS-1(-/-) mice exhibited increased susceptibility to WNV
      infection marked by enhanced viral replication and dissemination with early viral
      entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic
      cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS
      1-dependent RLR signaling was essential for triggering IFN defenses and
      controlling virus replication in these key target cells of infection.
      Intriguingly, infected IPS-1(-/-) mice displayed uncontrolled inflammation that
      included elevated systemic type I IFN, proinflammatory cytokine and chemokine
      responses, increased numbers of inflammatory DCs, enhanced humoral responses
      marked by complete loss of virus neutralization activity, and increased numbers
      of virus-specific CD8+ T cells and non-specific immune cell proliferation in the
      periphery and in the CNS. This uncontrolled inflammatory response was associated
      with a lack of regulatory T cell expansion that normally occurs during acute WNV
      infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was
      coupled with a failure to protect against WNV infection. Our data define an
      innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling
      that regulates the quantity, quality, and balance of the immune response to WNV
      infection.

PMID- 20140201
TI  - Fas/CD95 deficiency in ApcMin/+ mice increases intestinal tumor burden.
AB  - BACKGROUND: Fas, a member of the tumor necrosis family, is responsible for
      initiating the apoptotic pathway when bound to its ligand, Fas-L. Defects in the
      Fas-mediated apoptotic pathway have been reported in colorectal cancer.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a variant of the Apc(Min/+)
      mouse, a model for the human condition, Familial Adenomatous Polyposis (FAP), was
      generated with an additional deficiency of Fas (Apc(Min/+)/Fas(lpr)) by cross
      breeding Apc(Min/+) mice with Fas deficient (Fas(lpr)) mice. One of the main
      limitations of the Apc(Min/+) mouse model is that it only develops benign polyps.
      However, Apc(Min/+)/Fas(lpr) mice presented with a dramatic increase in tumor
      burden relative to Apc(Min/+) mice and invasive lesions at advanced ages.
      Proliferation and apoptosis markers revealed an increase in cellular
      proliferation, but negligible changes in apoptosis, while p53 increased at early
      ages. Fas-L was lower in Apc(Min/+)/Fas(lpr) mice relative to Apc(Min/+) cohorts,
      which resulted in enhanced inflammation. CONCLUSIONS/SIGNIFICANCE: This study
      demonstrated that imposition of a Fas deletion in an Apc(Min/+) background
      results in a more aggressive phenotype of the Apc(Min/+) mouse model, with more
      rapid development of invasive intestinal tumors and a decrease in Fas-L levels.

PMID- 20140202
TI  - Genomic approaches uncover increasing complexities in the regulatory landscape at
      the human SCL (TAL1) locus.
AB  - The SCL (TAL1) transcription factor is a critical regulator of haematopoiesis and
      its expression is tightly controlled by multiple cis-acting regulatory elements.
      To elaborate further the DNA elements which control its regulation, we used
      genomic tiling microarrays covering 256 kb of the human SCL locus to perform a
      concerted analysis of chromatin structure and binding of regulatory proteins in
      human haematopoietic cell lines. This approach allowed us to characterise further
      or redefine known human SCL regulatory elements and led to the identification of
      six novel elements with putative regulatory function both up and downstream of
      the SCL gene. They bind a number of haematopoietic transcription factors (GATA1,
      E2A LMO2, SCL, LDB1), CTCF or components of the transcriptional machinery and are
      associated with relevant histone modifications, accessible chromatin and low
      nucleosomal density. Functional characterisation shows that these novel elements
      are able to enhance or repress SCL promoter activity, have endogenous promoter
      function or enhancer-blocking insulator function. Our analysis opens up several
      areas for further investigation and adds new layers of complexity to our
      understanding of the regulation of SCL expression.

PMID- 20140203
TI  - Transient dimers of allergens.
AB  - BACKGROUND: Allergen-mediated cross-linking of IgE antibodies bound to the
      FcepsilonRI receptors on the mast cell surface is the key feature of the type I
      allergy. If an allergen is a homodimer, its allergenicity is enhanced because it
      would only need one type of antibody, instead of two, for cross-linking.
      METHODOLOGY/PRINCIPAL FINDINGS: An analysis of 55 crystal structures of allergens
      showed that 80% of them exist in symmetric dimers or oligomers in crystals. The
      majority are transient dimers that are formed at high protein concentrations that
      are reached in cells by colocalization. Native mass spectrometric analysis showed
      that native allergens do indeed form transient dimers in solution, while
      hypoallergenic variants of them exist almost solely in the monomeric form. We
      created a monomeric Bos d 5 allergen and show that it has a reduced capability to
      induce histamine release. CONCLUSIONS/SIGNIFICANCE: The results suggest that
      dimerization would be a very common and essential feature for allergens. Thus,
      the preparation of purely monomeric variants of allergens could open up novel
      possibilities for specific immunotherapy.

PMID- 20140204
TI  - Campylobacter jejuni colonization in wild birds: results from an infection
      experiment.
AB  - Campylobacter jejuni is a common cause of bacterial gastroenteritis in most parts
      of the world. The bacterium has a broad host range and has been isolated from
      many animals and environments. To investigate shedding patterns and putative
      effects on an avian host, we developed a colonization model in which a wild bird
      species, the European Robin Erithacus rubecula, was inoculated orally with C.
      jejuni from either a human patient or from another wild bird species, the Song
      Thrush Turdus philomelos. These two isolates were genetically distinct from each
      other and provoked very different host responses. The Song Thrush isolate
      colonized all challenged birds and colonization lasted 6.8 days on average. Birds
      infected with this isolate also showed a transient but significant decrease in
      body mass. The human isolate did not colonize the birds and could be detected
      only in the feces of the birds shortly after inoculation. European Robins
      infected with the wild bird isolate generated a specific antibody response to C.
      jejuni membrane proteins from the avian isolate, which also was cross-reactive to
      membrane proteins of the human isolate. In contrast, European Robins infected
      with the human isolate did not mount a significant response to bacterial membrane
      proteins from either of the two isolates. The difference in colonization ability
      could indicate host adaptations.

PMID- 20140205
TI  - Cofactor requirement of HpyAV restriction endonuclease.
AB  - BACKGROUND: Helicobacter pylori is the etiologic agent of common gastritis and a
      risk factor for gastric cancer. It is also one of the richest sources of Type II
      restriction-modification (R-M) systems in microorganisms. PRINCIPAL FINDINGS: We
      have cloned, expressed and purified a new restriction endonuclease HpyAV from H.
      pylori strain 26695. We determined the HpyAV DNA recognition sequence and
      cleavage site as CCTTC 6/5. In addition, we found that HpyAV has a unique metal
      ion requirement: its cleavage activity is higher with transition metal ions than
      in Mg(++). The special metal ion requirement of HpyAV can be attributed to the
      presence of a HNH catalytic site similar to ColE9 nuclease instead of the
      canonical PD-X-D/EXK catalytic site found in many other REases. Site-directed
      mutagenesis was carried out to verify the catalytic residues of HpyAV. Mutation
      of the conserved metal-binding Asn311 and His320 to alanine eliminated cleavage
      activity. HpyAV variant H295A displayed approximately 1% of wt activity.
      CONCLUSIONS/SIGNIFICANCE: Some HNH-type endonucleases have unique metal ion
      cofactor requirement for optimal activities. Homology modeling and site-directed
      mutagenesis confirmed that HpyAV is a member of the HNH nuclease family. The
      identification of catalytic residues in HpyAV paved the way for further
      engineering of the metal binding site. A survey of sequenced microbial genomes
      uncovered 10 putative R-M systems that show high sequence similarity to the HpyAV
      system, suggesting lateral transfer of a prototypic HpyAV-like R-M system among
      these microorganisms.

PMID- 20140206
TI  - beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the
      aryl hydrocarbon receptor.
AB  - BACKGROUND: Prostate cancer is a common and heterogeneous disease, where androgen
      receptor (AR) signaling plays a pivotal role in development and progression. The
      initial treatment for advanced prostate cancer is suppression of androgen
      signaling. Later on, essentially all patients develop an androgen independent
      stage which does not respond to anti hormonal treatment. Thus, alternative
      strategies targeting novel molecular mechanisms are required. beta-TrCP is an E3
      ligase that targets various substrates essential for many aspects of
      tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that beta-TrCP
      depletion suppresses prostate cancer and identify a relevant growth control
      mechanism. shRNA targeted against beta-TrCP reduced prostate cancer cell growth
      and cooperated with androgen ablation in vitro and in vivo. We found that beta
      TrCP inhibition leads to upregulation of the aryl hydrocarbon receptor (AhR)
      mediating the therapeutic effect. This phenomenon could be ligand independent, as
      the AhR ligand 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) did not alter prostate
      cancer cell growth. We detected high AhR expression and activation in basal cells
      and atrophic epithelial cells of human cancer bearing prostates. AhR expression
      and activation is also significantly higher in tumor cells compared to benign
      glandular epithelium. CONCLUSIONS/SIGNIFICANCE: Together these observations
      suggest that AhR activation may be a cancer counteracting mechanism in the
      prostate. We maintain that combining beta-TrCP inhibition with androgen ablation
      could benefit advanced prostate cancer patients.

PMID- 20140207
TI  - Analysis of high-throughput sequencing and annotation strategies for phage
      genomes.
AB  - BACKGROUND: Bacterial viruses (phages) play a critical role in shaping microbial
      populations as they influence both host mortality and horizontal gene transfer.
      As such, they have a significant impact on local and global ecosystem function
      and human health. Despite their importance, little is known about the genomic
      diversity harbored in phages, as methods to capture complete phage genomes have
      been hampered by the lack of knowledge about the target genomes, and difficulties
      in generating sufficient quantities of genomic DNA for sequencing. Of the
      approximately 550 phage genomes currently available in the public domain, fewer
      than 5% are marine phage. METHODOLOGY/PRINCIPAL FINDINGS: To advance the study of
      phage biology through comparative genomic approaches we used marine cyanophage as
      a model system. We compared DNA preparation methodologies (DNA extraction
      directly from either phage lysates or CsCl purified phage particles), and
      sequencing strategies that utilize either Sanger sequencing of a linker
      amplification shotgun library (LASL) or of a whole genome shotgun library (WGSL),
      or 454 pyrosequencing methods. We demonstrate that genomic DNA sample preparation
      directly from a phage lysate, combined with 454 pyrosequencing, is best suited
      for phage genome sequencing at scale, as this method is capable of capturing
      complete continuous genomes with high accuracy. In addition, we describe an
      automated annotation informatics pipeline that delivers high-quality annotation
      and yields few false positives and negatives in ORF calling.
      CONCLUSIONS/SIGNIFICANCE: These DNA preparation, sequencing and annotation
      strategies enable a high-throughput approach to the burgeoning field of phage
      genomics.

PMID- 20140208
TI  - A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks
      tumor growth in xenograft models.
AB  - Rabbit antibodies have been widely used in research and diagnostics due to their
      high antigen specificity and affinity. Though these properties are also highly
      desirable for therapeutic applications, rabbit antibodies have remained untapped
      for human disease therapy. To evaluate the therapeutic potential of rabbit
      monoclonal antibodies (RabMAbs), we generated a panel of neutralizing RabMAbs
      against human vascular endothelial growth factor-A (VEGF). These neutralizing
      RabMAbs are specific to VEGF and do not cross-react to other members of the VEGF
      protein family. Guided by sequence and lineage analysis of a panel of
      neutralizing RabMAbs, we humanized the lead candidate by substituting non
      critical residues with human residues within both the frameworks and the CDR
      regions. We showed that the humanized RabMAb retained its parental biological
      properties and showed potent inhibition of the growth of H460 lung carcinoma and
      A673 rhabdomyosarcoma xenografts in mice. These studies provide proof of
      principle for the feasibility of developing humanized RabMAbs as therapeutics.

PMID- 20140209
TI  - Regulation of gene expression in hepatic cells by the mammalian Target of
      Rapamycin (mTOR).
AB  - BACKGROUND: We investigated mTOR regulation of gene expression by studying
      rapamycin effect in two hepatic cell lines, the non-tumorigenic WB-F344 cells and
      the tumorigenic WB311 cells. The latter are resistant to the growth inhibitory
      effects of rapamycin, thus providing us with an opportunity to study the gene
      expression effects of rapamycin without confounding effects on cell
      proliferation. METHODOLOGY/PRINCIPAL FINDINGS: The hepatic cells were exposed to
      rapamycin for 24 hr. Microarray analysis on total RNA preparations identified
      genes that were affected by rapamycin in both cell lines and, therefore,
      modulated independent of growth arrest. Further studies showed that the promoter
      regions of these genes included E-box-containing transcription factor binding
      sites at higher than expected rates. Based on this, we tested the hypothesis that
      c-Myc is involved in regulation of gene expression by mTOR by comparing genes
      altered by rapamycin in the hepatic cells and by c-Myc induction in fibroblasts
      engineered to express c-myc in an inducible manner. Results showed enrichment for
      c-Myc targets among rapamycin sensitive genes in both hepatic cell lines.
      However, microarray analyses on wild type and c-myc null fibroblasts showed
      similar rapamycin effect, with the set of rapamycin-sensitive genes being
      enriched for c-Myc targets in both cases. CONCLUSIONS/SIGNIFICANCE: There is
      considerable overlap in the regulation of gene expression by mTOR and c-Myc.
      However, regulation of gene expression through mTOR is c-Myc-independent and
      cannot be attributed to the involvement of specific transcription factors
      regulated by the rapamycin-sensitive mTOR Complex 1.

PMID- 20140210
TI  - Generation of diversity in Streptococcus mutans genes demonstrated by MLST.
AB  - Streptococcus mutans, consisting of serotypes c, e, f and k, is an oral aciduric
      organism associated with the initiation and progression of dental caries. A total
      of 135 independent Streptococcus mutans strains from caries-free and caries
      active subjects isolated from various geographical locations were examined in two
      versions of an MLST scheme consisting of either 6 housekeeping genes [accC
      (acetyl-CoA carboxylase biotin carboxylase subunit), gki (glucokinase), lepA (GTP
      binding protein), recP (transketolase), sodA (superoxide dismutase), and tyrS
      (tyrosyl-tRNA synthetase)] or the housekeeping genes supplemented with 2
      extracellular putative virulence genes [gtfB (glucosyltransferase B) and spaP
      (surface protein antigen I/II)] to increase sequence type diversity. The number
      of alleles found varied between 20 (lepA) and 37 (spaP). Overall, 121 sequence
      types (STs) were defined using the housekeeping genes alone and 122 with all
      genes. However pi, nucleotide diversity per site, was low for all loci being in
      the range 0.019-0.007. The virulence genes exhibited the greatest nucleotide
      diversity and the recombination/mutation ratio was 0.67 [95% confidence interval
      0.3-1.15] compared to 8.3 [95% confidence interval 5.0-14.5] for the 6
      concatenated housekeeping genes alone. The ML trees generated for individual MLST
      loci were significantly incongruent and not significantly different from random
      trees. Analysis using ClonalFrame indicated that the majority of isolates were
      singletons and no evidence for a clonal structure or evidence to support serotype
      c strains as the ancestral S. mutans strain was apparent. There was also no
      evidence of a geographical distribution of individual isolates or that particular
      isolate clusters were associated with caries. The overall low sequence diversity
      suggests that S. mutans is a newly emerged species which has not accumulated
      large numbers of mutations but those that have occurred have been shuffled as a
      consequence of intra-species recombination generating genotypes which can be
      readily distinguished by sequence analysis.

PMID- 20140211
TI  - Gut microbiota in human adults with type 2 diabetes differs from non-diabetic
      adults.
AB  - BACKGROUND: Recent evidence suggests that there is a link between metabolic
      diseases and bacterial populations in the gut. The aim of this study was to
      assess the differences between the composition of the intestinal microbiota in
      humans with type 2 diabetes and non-diabetic persons as control. METHODS AND
      FINDINGS: The study included 36 male adults with a broad range of age and body
      mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2.
      The fecal bacterial composition was investigated by real-time quantitative PCR
      (qPCR) and in a subgroup of subjects (N = 20) by tag-encoded amplicon
      pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum
      Firmicutes and class Clostridia were significantly reduced in the diabetic group
      compared to the control group (P = 0.03). Furthermore, the ratios of
      Bacteroidetes to Firmicutes as well as the ratios of Bacteroides-Prevotella group
      to C. coccoides-E. rectale group correlated positively and significantly with
      plasma glucose concentration (P = 0.04) but not with BMIs. Similarly, class
      Betaproteobacteria was highly enriched in diabetic compared to non-diabetic
      persons (P = 0.02) and positively correlated with plasma glucose (P = 0.04).
      CONCLUSIONS: The results of this study indicate that type 2 diabetes in humans is
      associated with compositional changes in intestinal microbiota. The level of
      glucose tolerance should be considered when linking microbiota with metabolic
      diseases such as obesity and developing strategies to control metabolic diseases
      by modifying the gut microbiota.

PMID- 20140212
TI  - A top-performing algorithm for the DREAM3 gene expression prediction challenge.
AB  - A wealth of computational methods has been developed to address problems in
      systems biology, such as modeling gene expression. However, to objectively
      evaluate and compare such methods is notoriously difficult. The DREAM (Dialogue
      on Reverse Engineering Assessments and Methods) project is a community-wide
      effort to assess the relative strengths and weaknesses of different computational
      methods for a set of core problems in systems biology. This article presents a
      top-performing algorithm for one of the challenge problems in the third annual
      DREAM (DREAM3), namely the gene expression prediction challenge. In this
      challenge, participants are asked to predict the expression levels of a small set
      of genes in a yeast deletion strain, given the expression levels of all other
      genes in the same strain and complete gene expression data for several other
      yeast strains. I propose a simple -nearest-neighbor (KNN) method to solve this
      problem. Despite its simplicity, this method works well for this challenge,
      sharing the "top performer" honor with a much more sophisticated method. I also
      describe several alternative, simple strategies, including a modified KNN
      algorithm that further improves the performance of the standard KNN method. The
      success of these methods suggests that complex methods attempting to integrate
      multiple data sets do not necessarily lead to better performance than simple yet
      robust methods. Furthermore, none of these top-performing methods, including the
      one by a different team, are based on gene regulatory networks, which seems to
      suggest that accurately modeling gene expression using gene regulatory networks
      is unfortunately still a difficult task.

PMID- 20140213
TI  - Greedy selection of species for ancestral state reconstruction on phylogenies:
      elimination is better than insertion.
AB  - Accurate reconstruction of ancestral character states on a phylogeny is crucial
      in many genomics studies. We study how to select species to achieve the best
      reconstruction of ancestral character states on a phylogeny. We first show that
      the marginal maximum likelihood has the monotonicity property that more taxa give
      better reconstruction, but the Fitch method does not have it even on an
      ultrametric phylogeny. We further validate a greedy approach for species
      selection using simulation. The validation tests indicate that backward greedy
      selection outperforms forward greedy selection. In addition, by applying our
      selection strategy, we obtain a set of the ten most informative species for the
      reconstruction of the genomic sequence of the so-called boreoeutherian ancestor
      of placental mammals. This study has broad relevance in comparative genomics and
      paleogenomics since limited research resources do not allow researchers to
      sequence the large number of descendant species required to reconstruct an
      ancestral sequence.

PMID- 20140215
TI  - MutS and MutL are dispensable for maintenance of the genomic mutation rate in the
      halophilic archaeon Halobacterium salinarum NRC-1.
AB  - BACKGROUND: The genome of the halophilic archaeon Halobacterium salinarum NRC-1
      encodes for homologs of MutS and MutL, which are key proteins of a DNA mismatch
      repair pathway conserved in Bacteria and Eukarya. Mismatch repair is essential
      for retaining the fidelity of genetic information and defects in this pathway
      result in the deleterious accumulation of mutations and in hereditary diseases in
      humans. METHODOLOGY/PRINCIPAL FINDINGS: We calculated the spontaneous genomic
      mutation rate of H. salinarum NRC-1 using fluctuation tests targeting genes of
      the uracil monophosphate biosynthesis pathway. We found that H. salinarum NRC-1
      has a low incidence of mutation suggesting the presence of active mechanisms to
      control spontaneous mutations during replication. The spectrum of mutational
      changes found in H. salinarum NRC-1, and in other archaea, appears to be unique
      to this domain of life and might be a consequence of their adaption to extreme
      environmental conditions. In-frame targeted gene deletions of H. salinarum NRC-1
      mismatch repair genes and phenotypic characterization of the mutants demonstrated
      that the mutS and mutL genes are not required for maintenance of the observed
      mutation rate. CONCLUSIONS/SIGNIFICANCE: We established that H. salinarum NRC-1
      mutS and mutL genes are redundant to an alternative system that limits
      spontaneous mutation in this organism. This finding leads to the puzzling
      question of what mechanism is responsible for maintenance of the low genomic
      mutation rates observed in the Archaea, which for the most part do not have MutS
      and MutL homologs.

PMID- 20140214
TI  - Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results
      of a phase 1 randomized controlled trial.
AB  - BACKGROUND: The objective was to evaluate the safety and immunogenicity of the
      AMA1-based malaria vaccine FMP2.1/AS02(A) in children exposed to seasonal
      falciparum malaria. METHODOLOGY/PRINCIPAL FINDINGS: A Phase 1 double blind
      randomized controlled dose escalation trial was conducted in Bandiagara, Mali,
      West Africa, a rural town with intense seasonal transmission of Plasmodium
      falciparum malaria. The malaria vaccine FMP2.1/AS02(A) is a recombinant protein
      (FMP2.1) based on apical membrane antigen 1 (AMA1) from the 3D7 clone of P.
      falciparum, formulated in the Adjuvant System AS02(A). The comparator vaccine was
      a cell-culture rabies virus vaccine (RabAvert). One hundred healthy Malian
      children aged 1-6 years were recruited into 3 cohorts and randomized to receive
      either 10 microg FMP2.1 in 0.1 mL AS02(A), or 25 microg FMP2.1 in 0.25 mL
      AS02(A), or 50 microg FMP2.1 50 microg in 0.5 mL AS02(A), or rabies vaccine.
      Three doses of vaccine were given at 0, 1 and 2 months, and children were
      followed for 1 year. Solicited symptoms were assessed for 7 days and unsolicited
      symptoms for 30 days after each vaccination. Serious adverse events were assessed
      throughout the study. Transient local pain and swelling were common and more
      frequent in all malaria vaccine dosage groups than in the comparator group, but
      were acceptable to parents of participants. Levels of anti-AMA1 antibodies
      measured by ELISA increased significantly (at least 100-fold compared to
      baseline) in all 3 malaria vaccine groups, and remained high during the year of
      follow up. CONCLUSION/SIGNIFICANCE: The FMP2.1/AS02(A) vaccine had a good safety
      profile, was well-tolerated, and induced high and sustained antibody levels in
      malaria-exposed children. This malaria vaccine is being evaluated in a Phase 2
      efficacy trial in children at this site. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00358332 [NCT00358332].

PMID- 20140216
TI  - International migration of doctors, and its impact on availability of
      psychiatrists in low and middle income countries.
AB  - BACKGROUND: Migration of health professionals from low and middle income
      countries to rich countries is a large scale and long-standing phenomenon, which
      is detrimental to the health systems in the donor countries. We sought to explore
      the extent of psychiatric migration. METHODS: In our study, we use the respective
      professional databases in each country to establish the numbers of psychiatrists
      currently registered in the UK, US, New Zealand, and Australia who originate from
      other countries. We also estimate the impact of this migration on the
      psychiatrist population ratios in the donor countries. FINDINGS: We document
      large numbers of psychiatrists currently registered in the UK, US, New Zealand
      and Australia originating from India (4687 psychiatrists), Pakistan (1158),
      Bangladesh (149), Nigeria (384), Egypt (484), Sri Lanka (142), Philippines
      (1593). For some countries of origin, the numbers of psychiatrists currently
      registered within high-income countries' professional databases are very small
      (e.g., 5 psychiatrists of Tanzanian origin registered in the 4 high-income
      countries we studied), but this number is very significant compared to the 15
      psychiatrists currently registered in Tanzania). Without such emigration, many
      countries would have more than double the number of psychiatrists per 100,000
      population (e.g. Bangladesh, Myanmar, Afghanistan, Egypt, Syria, Lebanon); and
      some countries would have had five to eight times more psychiatrists per 100,000
      (e.g. Philippines, Pakistan, Sri Lanka, Liberia, Nigeria and Zambia).
      CONCLUSIONS: Large numbers of psychiatrists originating from key low and middle
      income countries are currently registered in the UK, US, New Zealand and
      Australia, with concomitant impact on the psychiatrist/population ratio n the
      originating countries. We suggest that creative international policy approaches
      are needed to ensure the individual migration rights of health professionals do
      not compromise societal population rights to health, and that there are public
      and fair agreements between countries within an internationally agreed framework.

PMID- 20140217
TI  - Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system
      components: temporal profiling of gene expression in alpha9 null mice.
AB  - BACKGROUND: It has previously been shown that deletion of chrna9, the gene
      encoding the alpha9 nicotinic acetylcholine receptor (nAChR) subunit, results in
      abnormal synaptic terminal structure. Additionally, all nAChR-mediated cochlear
      activity is lost, as characterized by a failure of the descending efferent system
      to suppress cochlear responses to sound. In an effort to characterize the
      molecular mechanisms underlying the structural and functional consequences
      following loss of alpha9 subunit expression, we performed whole-transcriptome
      gene expression analyses on cochleae of wild type and alpha9 knockout (alpha9(-/
      )) mice during postnatal days spanning critical periods of synapse formation and
      maturation. PRINCIPAL FINDINGS: Data revealed that loss of alpha9 receptor
      subunit expression leads to an up-regulation of genes involved in synaptic
      transmission and ion channel activity. Unexpectedly, loss of alpha9 receptor
      subunit expression also resulted in an increased expression of genes encoding
      GABA receptor subunits and the GABA synthetic enzyme, glutamic acid
      decarboxylase. These data suggest the existence of a previously unrecognized
      association between the nicotinic cholinergic and GABAergic systems in the
      cochlea. Computational analyses have highlighted differential expression of
      several gene sets upon loss of nicotinic cholinergic activity in the cochlea.
      Time-series analysis of whole transcriptome patterns, represented as self
      organizing maps, revealed a disparate pattern of gene expression between alpha9(
      /-) and wild type cochleae at the onset of hearing (P13), with knockout samples
      resembling immature postnatal ages. CONCLUSIONS: We have taken a systems biology
      approach to provide insight into molecular programs influenced by the loss of
      nicotinic receptor-based cholinergic activity in the cochlea and to identify
      candidate genes that may be involved in nicotinic cholinergic synapse formation,
      stabilization or function within the inner ear. Additionally, our data indicate a
      change in the GABAergic system upon loss of alpha9 nicotinic receptor subunit
      within the cochlea.

PMID- 20140218
TI  - Reduced cul-5 activity causes aberrant follicular morphogenesis and germ cell
      loss in Drosophila oogenesis.
AB  - Drosophila oogenesis is especially well suited for studying stem cell biology,
      cellular differentiation, and morphogenesis. The small modifier protein ubiquitin
      regulates many cellular pathways. Ubiquitin is conjugated to target proteins by a
      diverse class of enzymes called ubiquitin E3 ligases. Here we characterize the
      requirement of Cul-5, a key component of a subgroup of Cullin-RING-type ubiquitin
      E3 ligases, in Drosophila oogenesis. We find that reduced cul-5 activity causes
      the formation of aberrant follicles that are characterized by excess germ cells.
      We show that germ line cells overproliferate in cul-5 mutant females, causing the
      formation of abnormally large germ line cysts. Also, the follicular epithelium
      that normally encapsulates single germ line cysts develops aberrantly in cul-5
      mutant, leading to defects in cyst formation. We additionally found that Cul-5 is
      required for germ cell maintenance, as germ cells are depleted in a substantial
      fraction of cul-5 mutant ovaries. All of these cul-5 phenotypes are strongly
      enhanced by reduced activity of gustavus (gus), which encodes a substrate
      receptor of Cul-5-based ubiquitin E3 ligases. Taken together, our results
      implicate Cul-5/Gus ubiquitin E3 ligases in ovarian tissue morphogenesis, germ
      cell proliferation and maintenance of the ovarian germ cell population.

PMID- 20140219
TI  - Role of QuantiFERON-TB gold, interferon gamma inducible protein-10 and tuberculin
      skin test in active tuberculosis diagnosis.
AB  - BACKGROUND: The measurement of Interferon gamma or Interferon gamma inducible
      protein (IP)-10 in antigen stimulated blood samples is suggested as an
      alternative method for latent tuberculosis (TB) diagnosis. Nonetheless, their
      role in active TB diagnosis, particularly in TB endemic settings is yet to be
      defined. In this study, the sensitivities and specificities of Interferon gamma
      release assay (IGRA), IP-10 assay and tuberculin skin test (TST) in detecting
      active TB cases were assessed in human immunodeficiency virus (HIV) sero-negative
      TB patients and healthy controls respectively. METHODS/PRINCIPAL FINDINGS: A
      total of 177 adult TB patients and 100 healthy controls were included for this
      study. QuantiFERON-TB Gold In-tube (QFT-IT) method was used to analyze the
      sensitivity and specificity of IGRA. QFT-IT, IP-10 and TST yielded the diagnostic
      sensitivities of 90.6% (95%CI: 86.3%-94.9%), 92.5% (95%CI: 88.6%-96.4%) and 68.9%
      (95%CI: 60.6%-77.2%) and specificities of 55% (95% CI: 35.2%-54.8%), 48% (95% CI:
      38.2%-57.8%) and 75.5% (95% CI: 66.8%-84.2%), respectively. The extent of
      pulmonary involvement or presence of diabetes mellitus did not appear to
      influence the sensitivities of any of these tests. The combination of any of the
      two tests among QFT-IT, IP-10 and TST showed >98% sensitivity among smear
      negative cases and particularly the combination of IP-10, TST and smear
      microscopy showed 100% sensitivity, however, the specificity was decreased to
      44.8%. CONCLUSIONS/SIGNIFICANCE: QFT-IT and IP-10 were highly sensitive in
      detecting active TB cases. The combination with TST improved the sensitivity of
      QFT-IT and IP-10 significantly. Although the higher sensitivity of combination of
      QFT-IT/IP-10 and TST may be useful in active TB diagnosis, they are limited by
      their poor specificity due to the high prevalence of latent TB in our settings.

PMID- 20140220
TI  - Differential patterns of infection and disease with P. falciparum and P. vivax in
      young Papua New Guinean children.
AB  - BACKGROUND: Where P. vivax and P. falciparum occur in the same population, the
      peak burden of P. vivax infection and illness is often concentrated in younger
      age groups. Experiences from malaria therapy patients indicate that immunity is
      acquired faster to P. vivax than to P. falciparum challenge. There is however
      little prospective data on the comparative risk of infection and disease from
      both species in young children living in co-endemic areas. METHODOLOGY/PRINCIPAL
      FINDINGS: A cohort of 264 Papua New Guinean children aged 1-3 years (at
      enrolment) were actively followed-up for Plasmodium infection and febrile illness
      for 16 months. Infection status was determined by light microscopy and PCR every
      8 weeks and at each febrile episode. A generalised estimating equation (GEE)
      approach was used to analyse both prevalence of infection and incidence of
      clinical episodes. A more pronounced rise in prevalence of P. falciparum compared
      to P. vivax infection was evident with increasing age. Although the overall
      incidence of clinical episodes was comparable (P. falciparum: 2.56, P. vivax 2.46
      episodes / child / yr), P. falciparum and P. vivax infectious episodes showed
      strong but opposing age trends: P. falciparum incidence increased until the age
      of 30 months with little change thereafter, but incidence of P. vivax decreased
      significantly with age throughout the entire age range. For P. falciparum, both
      prevalence and incidence of P. falciparum showed marked seasonality, whereas only
      P. vivax incidence but not prevalence decreased in the dry season.
      CONCLUSIONS/SIGNIFICANCE: Under high, perennial exposure, children in PNG begin
      acquiring significant clinical immunity, characterized by an increasing ability
      to control parasite densities below the pyrogenic threshold to P. vivax, but not
      to P. falciparum, in the 2(nd) and 3(rd) year of life. The ability to relapse
      from long-lasting liver-stages restricts the seasonal variation in prevalence of
      P. vivax infections.

PMID- 20140221
TI  - Performance of epigenetic markers SEPT9 and ALX4 in plasma for detection of
      colorectal precancerous lesions.
AB  - BACKGROUND: Screening for colorectal cancer (CRC) has shown to reduce cancer
      related mortality, however, acceptance and compliance to current programmes are
      poor. Developing new, more acceptable non-invasive tests for the detection of
      cancerous and precancerous colorectal lesions would not only allow preselection
      of individuals for colonoscopy, but may also prevent cancer by removal of
      precancerous lesions. METHODS: Plasma from 128 individuals (cohort I -
      exploratory study: 73 cases / 55 controls) was used to test the performance of a
      single marker, SEPT9, using a real-time quantitative PCR assay. To validate
      performance of SEPT9, plasma of 76 individuals (cohort II - validation study: 54
      cases / 22 controls) was assessed. Additionally, improvement of predictive
      capability considering SEPT9 and additionally ALX4 methylation was investigated
      within these patients. RESULTS: In both cohorts combined, methylation of SEPT9
      was observed in 9% of controls (3/33), 29% of patients with colorectal
      precancerous lesions (27/94) and 73% of colorectal cancer patients (24/33). The
      presence of both SEPT9 and ALX4 markers was analysed in cohort II and was
      observed in 5% of controls (1/22) and 37% of patients with polyps (18/49).
      Interestingly, also 3/5 (60%) patients with colorectal cancer were tested
      positive by the two marker panel in plasma. CONCLUSIONS: While these data confirm
      the detection rate of SEPT9 as a biomarker for colorectal cancer, they also show
      that methylated DNA from advanced precancerous colorectal lesions can be detected
      using a panel of two DNA methylation markers, ALX4 and SEPT9. If confirmed in
      larger studies these data indicate that screening for colorectal precancerous
      lesions with a blood-based test may be as feasible as screening for invasive
      cancer.

PMID- 20140222
TI  - VAV2 and VAV3 as candidate disease genes for spontaneous glaucoma in mice and
      humans.
AB  - BACKGROUND: Glaucoma is a leading cause of blindness worldwide. Nonetheless, the
      mechanism of its pathogenesis has not been well-elucidated, particularly at the
      molecular level, because of insufficient availability of experimental genetic
      animal models. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that
      deficiency of Vav2 and Vav3, guanine nucleotides exchange factors for Rho
      guanosine triphosphatases, leads to an ocular phenotype similar to human
      glaucoma. Vav2/Vav3-deficient mice, and to a lesser degree Vav2-deficient mice,
      show early onset of iridocorneal angle changes and elevated intraocular pressure,
      with subsequent selective loss of retinal ganglion cells and optic nerve head
      cupping, which are the hallmarks of glaucoma. The expression of Vav2 and Vav3
      tissues was demonstrated in the iridocorneal angle and retina in both mouse and
      human eyes. In addition, a genome-wide association study screening glaucoma
      susceptibility loci using single nucleotide polymorphisms analysis identified
      VAV2 and VAV3 as candidates for associated genes in Japanese open-angle glaucoma
      patients. CONCLUSIONS/SIGNIFICANCE: Vav2/Vav3-deficient mice should serve not
      only as a useful murine model of spontaneous glaucoma, but may also provide a
      valuable tool in understanding of the pathogenesis of glaucoma in humans,
      particularly the determinants of altered aqueous outflow and subsequent elevated
      intraocular pressure.

PMID- 20140223
TI  - Ribosylation rapidly induces alpha-synuclein to form highly cytotoxic molten
      globules of advanced glycation end products.
AB  - BACKGROUND: Alpha synuclein (alpha-Syn) is the main component of Lewy bodies
      which are associated with several neurodegenerative diseases such as Parkinson's
      disease. While the glycation with D-glucose that results in alpha-Syn misfold and
      aggregation has been studied, the effects of glycation with D-ribose on alpha-Syn
      have not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that
      ribosylation induces alpha-Syn misfolding and generates advanced glycation end
      products (AGEs) which form protein molten globules with high cytotoxcity. Results
      from native- and SDS-PAGE showed that D-ribose reacted rapidly with alpha-Syn,
      leading to dimerization and polymerization. Trypsin digestion and sequencing
      analysis revealed that during ribosylation the lysinyl residues (K(58), K(60),
      K(80), K(96), K(97) and K(102)) in the C-terminal region reacted more quickly
      with D-ribose than those of the N-terminal region. Using Western blotting, AGEs
      resulting from the glycation of alpha-Syn were observed within 24 h in the
      presence of D-ribose, but were not observed in the presence of D-glucose. Changes
      in fluorescence at 410 nm demonstrated again that AGEs were formed during early
      ribosylation. Changes in the secondary structure of ribosylated alpha-Syn were
      not clearly detected by CD spectrometry in studies on protein conformation.
      However, intrinsic fluorescence at 310 nm decreased markedly in the presence of D
      ribose. Observations with atomic force microscopy showed that the surface
      morphology of glycated alpha-Syn looked like globular aggregates. thioflavin T
      (ThT) fluorescence increased during alpha-Syn incubation regardless of
      ribosylation. As incubation time increased, ribosylation of alpha-Syn resulted in
      a blue-shift (approximately 100 nm) in the fluorescence of ANS. The light
      scattering intensity of ribosylated alpha-Syn was not markedly different from
      native alpha-Syn, suggesting that ribosylated alpha-Syn is present as molten
      protein globules. Ribosylated products had a high cytotoxicity to SH-SY5Y cells,
      leading to LDH release and increase in the levels of reactive oxygen species
      (ROS). CONCLUSIONS/SIGNIFICANCE: alpha-Syn is rapidly glycated in the presence of
      D-ribose generating molten globule-like aggregations which cause cell oxidative
      stress and result in high cytotoxicity.

PMID- 20140224
TI  - Gene expression profiling and network analysis reveals lipid and steroid
      metabolism to be the most favored by TNFalpha in HepG2 cells.
AB  - BACKGROUND: The proinflammatory cytokine, TNFalpha, is a crucial mediator of the
      pathogenesis of several diseases, more so in cases involving the liver wherein it
      is critical in maintaining liver homeostasis since it is a major determiner of
      hepatocyte life and death. Gene expression profiling serves as an appropriate
      strategy to unravel the underlying signatures to envisage such varied responses
      and considering this, gene transcription profiling was examined in control and
      TNFalpha treated HepG2 cells. METHODS AND FINDINGS: Microarray experiments
      between control and TNFalpha treated HepG2 cells indicated that TNFalpha could
      significantly alter the expression profiling of 140 genes; among those up
      regulated, several GO (Gene Ontology) terms related to lipid and fat metabolism
      were significantly (p<0.01) overrepresented indicating a global preference of fat
      metabolism within the hepatocyte and those within the down-regulated dataset
      included genes involved in several aspects of the immune response like
      immunoglobulin receptor activity and IgE binding thereby indicating a compromise
      in the immune defense mechanism(s). Conserved transcription factor binding sites
      were identified in identically clustered genes within a common GO term and SREBP
      1 and FOXJ2 depicted increased occupation of their respective binding elements in
      the presence of TNFalpha. The interacting network of "lipid metabolism, small
      molecule biochemistry" was derived to be significantly overrepresented that
      correlated well with the top canonical pathway of "biosynthesis of steroids".
      CONCLUSIONS: TNFalpha alters the transcriptome profiling within HepG2 cells with
      an interesting catalog of genes being affected and those involved in lipid and
      steroid metabolism to be the most favored. This study represents a composite
      analysis of the effects of TNFalpha in HepG2 cells that encompasses the altered
      transcriptome profiling, the functional analysis of the up- and down- regulated
      genes and the identification of conserved transcription factor binding sites.
      These could possibly determine TNFalpha mediated alterations mainly the
      phenotypes of hepatic steatosis and fatty liver associated with several hepatic
      pathological states.

PMID- 20140225
TI  - Microgravity promotes differentiation and meiotic entry of postnatal mouse male
      germ cells.
AB  - A critical step of spermatogenesis is the entry of mitotic spermatogonia into
      meiosis. Progresses on these topics are hampered by the lack of an in vitro
      culture system allowing mouse spermatogonia differentiation and entry into
      meiosis. Previous studies have shown that mouse pachytene spermatocytes cultured
      in simulated microgravity (SM) undergo a spontaneous meiotic progression. Here we
      report that mouse mitotic spermatogonia cultured under SM with a rotary cell
      culture system (RCCS) enter into meiosis in the absence of any added exogenous
      factor or contact with somatic cells. We found that isolated Kit-positive
      spermatogonia under the RCCS condition enter into the prophase of the first
      meiotic division (leptotene stage), as monitored by chromosomal organization of
      the synaptonemal complex 3 protein (Scp3) and up-regulation of several pro
      meiotic genes. SM was found to activate the phosphatidyl inositol 3 kinase (PI3K)
      pathway and to induce in Kit-positive spermatogonia the last round of DNA
      replication, typical of the preleptotene stage. A PI3K inhibitor abolished Scp3
      induction and meiotic entry stimulated by RCCS conditions. A positive effect of
      SM on germ cell differentiation was also observed in undifferentiated (Kit
      negative) spermatogonia, in which RCCS conditions stimulate the expression of Kit
      and Stra8. In conclusion, SM is an artificial environmental condition which
      promotes postnatal male germ cell differentiation and might provide a tool to
      study the molecular mechanisms underlying the switch from mitosis to meiosis in
      mammals.

PMID- 20140226
TI  - F-actin binding regions on the androgen receptor and huntingtin increase
      aggregation and alter aggregate characteristics.
AB  - Protein aggregation is associated with neurodegeneration. Polyglutamine expansion
      diseases such as spinobulbar muscular atrophy and Huntington disease feature
      proteins that are destabilized by an expanded polyglutamine tract in their N
      termini. It has previously been reported that intracellular aggregation of these
      target proteins, the androgen receptor (AR) and huntingtin (Htt), is modulated by
      actin-regulatory pathways. Sequences that flank the polyglutamine tract of AR and
      Htt might influence protein aggregation and toxicity through protein-protein
      interactions, but this has not been studied in detail. Here we have evaluated an
      N-terminal 127 amino acid fragment of AR and Htt exon 1. The first 50 amino acids
      of ARN127 and the first 14 amino acids of Htt exon 1 mediate binding to
      filamentous actin in vitro. Deletion of these actin-binding regions renders the
      polyglutamine-expanded forms of ARN127 and Htt exon 1 less aggregation-prone, and
      increases the SDS-solubility of aggregates that do form. These regions thus
      appear to alter the aggregation frequency and type of polyglutamine-induced
      aggregation. These findings highlight the importance of flanking sequences in
      determining the propensity of unstable proteins to misfold.

PMID- 20140227
TI  - CpG methylation of a silent controlling element in the murine Avy allele is
      incomplete and unresponsive to methyl donor supplementation.
AB  - BACKGROUND: The viable yellow allele of agouti (A(vy)) is remarkable for its
      unstable and partially heritable epigenetic state, which produces wide variation
      in phenotypes of isogenic mice. In the A(vy) allele an inserted intracisternal A
      particle (IAP) acts as a controlling element which deregulates expression of
      agouti by transcription from the LTR of the IAP; the phenotypic state has been
      linked to CpG methylation of the LTR. Phenotypic variation between A(vy) mice
      indicates that the epigenetic state of the IAP is unstable in the germline.
      PRINCIPAL FINDINGS: We have made a detailed examination of somatic methylation of
      the IAP using bisulphite allelic sequencing, and find that the promoter is
      incompletely methylated even when it is transcriptionally silent. In utero
      exposure to supplementary methyl donors, which alters the spectrum of A(vy)
      phenotypes, does not increase the density of CpG methylation in the silent LTR.
      CONCLUSIONS: Our findings suggest that, contrary to previous supposition, methyl
      donor supplementation acts through an indirect mechanism to silence A(vy). The
      incomplete cytosine methylation we observe at the somatically silent A(vy) allele
      may reflect its unstable germline state, and the influence of epigenetic
      modifications underlying CpG methylation.

PMID- 20140228
TI  - Classification of genes and putative biomarker identification using distribution
      metrics on expression profiles.
AB  - BACKGROUND: Identification of genes with switch-like properties will facilitate
      discovery of regulatory mechanisms that underlie these properties, and will
      provide knowledge for the appropriate application of Boolean networks in gene
      regulatory models. As switch-like behavior is likely associated with tissue
      specific expression, these gene products are expected to be plausible candidates
      as tissue-specific biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: In a systematic
      classification of genes and search for biomarkers, gene expression profiles
      (GEPs) of more than 16,000 genes from 2,145 mouse array samples were analyzed.
      Four distribution metrics (mean, standard deviation, kurtosis and skewness) were
      used to classify GEPs into four categories: predominantly-off, predominantly-on,
      graded (rheostatic), and switch-like genes. The arrays under study were also
      grouped and examined by tissue type. For example, arrays were categorized as
      'brain group' and 'non-brain group'; the Kolmogorov-Smirnov distance and Pearson
      correlation coefficient were then used to compare GEPs between brain and non
      brain for each gene. We were thus able to identify tissue-specific biomarker
      candidate genes. CONCLUSIONS/SIGNIFICANCE: The methodology employed here may be
      used to facilitate disease-specific biomarker discovery.

PMID- 20140231
TI  - Inverse Correlation Between an Organ's Cancer Rate and Its Evolutionary
      Antiquity.
AB  - Human cancer rates vary dramatically across the range of internal organs in the
      body, but there is no single model to explain the variation and there is also no
      obvious overall pattern to it. Theories have been proposed to account for high
      rates in particularly cancer-prone organs, and they usually concentrate on the
      peculiar vulnerability of certain cells to mutation (e.g., lung cells' direct
      exposure to airborne carcinogens). These explanations are valuable for
      understanding mechanisms of disease and also for cancer prevention, but they
      address neither the overall distribution of cancers nor the possibility that some
      states of differentiation may be intrinsically less stable than others to the
      effects of random mutation, a possibility predicted on purely theoretical grounds
      many years ago. This brief report describes an overall pattern to human organ
      specific cancer incidence data and shows that organ-specific cancer rates
      correlate negatively with an organ's evolutionary antiquity. Although the
      relationship may just be coincidental, it suggests the possibility that recently
      evolved differentiation states may be intricnsically more vulnerable to
      neoplastic change. Extrapolation of the regression line to a cancer incidence of
      zero equates to a level of tissue organization typical of 660 Myr ago; the
      inferred beginning of neoplasia therefore coincides with the rise of complex
      multicellular animals.

PMID- 20140229
TI  - Staphylococcal PknB as the first prokaryotic representative of the proline
      directed kinases.
AB  - In eukaryotic cell types, virtually all cellular processes are under control of
      proline-directed kinases and especially MAP kinases. Serine/threonine kinases in
      general were originally considered as a eukaryote-specific enzyme family.
      However, recent studies have revealed that orthologues of eukaryotic
      serine/threonine kinases exist in bacteria. Moreover, various pathogenic species,
      such as Yersinia and Mycobacterium, require serine/threonine kinases for
      successful invasion of human host cells. The substrates targeted by bacterial
      serine/threonine kinases have remained largely unknown. Here we report that the
      serine/threonine kinase PknB from the important pathogen Staphylococcus aureus is
      released into the external milieu, which opens up the possibility that PknB does
      not only phosphorylate bacterial proteins but also proteins of the human host. To
      identify possible human targets of purified PknB, we studied in vitro
      phosphorylation of peptide microarrays and detected 68 possible human targets for
      phosphorylation. These results show that PknB is a proline-directed kinase with
      MAP kinase-like enzymatic activity. As the potential cellular targets for PknB
      are involved in apoptosis, immune responses, transport, and metabolism, PknB
      secretion may help the bacterium to evade intracellular killing and facilitate
      its growth. In apparent agreement with this notion, phosphorylation of the host
      cell response coordinating transcription factor ATF-2 by PknB was confirmed by
      mass spectrometry. Taken together, our results identify PknB as the first
      prokaryotic representative of the proline-directed kinase/MAP kinase family of
      enzymes.

PMID- 20140230
TI  - Designed coiled-coil peptides inhibit the type three secretion system of
      enteropathogenic Escherichia coli.
AB  - BACKGROUND: Enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC)
      are two categories of E. coli strains associated with human disease. A major
      virulence factor of both pathotypes is the expression of a type three secretion
      system (TTSS), responsible for their ability to adhere to gut mucosa causing a
      characteristic attaching and effacing lesion (A/E). The TTSS translocates
      effector proteins directly into the host cell that subvert mammalian cell
      biochemistry. METHODS/PRINCIPAL FINDINGS: We examined synthetic peptides designed
      to inhibit the TTSS. CoilA and CoilB peptides, both representing coiled-coil
      regions of the translocator protein EspA, and CoilD peptide, corresponding to a
      coiled-coil region of the needle protein EscF, were effective in inhibiting the
      TTSS dependent hemolysis of red blood cells by the EPEC E2348/69 strain. CoilA
      and CoilB peptides also reduced the formation of actin pedestals by the same
      strain in HEp-2 cells and impaired the TTSS-mediated protein translocation into
      the epithelial cell. Interestingly, CoilA and CoilB were able to block EspA
      assembly, destabilizing the TTSS and thereby Tir translocation. This blockage of
      EspA polymerization by CoilA or CoilB peptides, also inhibited the correct
      delivery of EspB and EspD as detected by immunoblotting. Interestingly, electron
      microscopy of bacteria incubated with the CoilA peptide showed a reduction of the
      length of EspA filaments. CONCLUSIONS: Our data indicate that coiled-coil
      peptides can prevent the assembly and thus the functionality of the TTSS
      apparatus and suggest that these peptides could provide an attractive tool to
      block EPEC and EHEC pathogenesis.

PMID- 20140232
TI  - Fine-tuning of early events in the jasmonate response.
AB  - Jasmonates (JAs) control many aspects of plant defense and development, for
      instance by inhibiting growth and eliciting secondary metabolism. The mechanisms
      by which JAs regulate these processes are currently under intensive
      investigation. Examination of transcriptional changes upon methyl jasmonate
      (MeJA) perception in a fast-growing Arabidopsis thaliana cell suspension culture
      revealed a quick and direct dual effect of JAs on the plant's cellular processes.
      Simultaneously, JA-elicited Arabidopsis cells activated phenylpropanoid
      metabolism and repressed cell cycle progression. Early JA response genes were
      predominantly implicated in transcriptional regulation and JA biosynthesis. In
      two parallel screens, we identified both early responsive transcriptional
      activators (ORA47 and MYC2) and transcriptional repressors (STZ/ZAT10 and AZF2)
      that putatively regulate the expression of the JA biosynthesis gene LOX3. In this
      addendum, we provide additional data demonstrating that MYC2, STZ/ZAT10 and AZF2
      might also control the expression of JAZ1/TIFY10a that encodes a key repressor in
      the JA signaling cascade.

PMID- 20140233
TI  - Dynamics of the bacterial intermediate filament crescentin in vitro and in vivo.
AB  - BACKGROUND: Crescentin, the recently discovered bacterial intermediate filament
      protein, organizes into an extended filamentous structure that spans the length
      of the bacterium Caulobacter crescentus and plays a critical role in defining its
      curvature. The mechanism by which crescentin mediates cell curvature and whether
      crescentin filamentous structures are dynamic and/or polar are not fully
      understood. METHODOLOGY/PRINCIPAL FINDINGS: Using light microscopy, electron
      microscopy and quantitative rheology, we investigated the mechanics and dynamics
      of crescentin structures. Live-cell microscopy reveals that crescentin forms
      structures in vivo that undergo slow remodeling. The exchange of subunits between
      these structures and a pool of unassembled subunits is slow during the life cycle
      of the cell however; in vitro assembly and gelation of C. crescentus crescentin
      structures are rapid. Moreover, crescentin forms filamentous structures that are
      elastic, solid-like, and, like other intermediate filaments, can recover a
      significant portion of their network elasticity after shear. The assembly
      efficiency of crescentin is largely unaffected by monovalent cations (K(+),
      Na(+)), but is enhanced by divalent cations (Mg(2+), Ca(2+)), suggesting that the
      assembly kinetics and micromechanics of crescentin depend on the valence of the
      ions present in solution. CONCLUSIONS/SIGNIFICANCE: These results indicate that
      crescentin forms filamentous structures that are elastic, labile, and stiff, and
      that their low dissociation rate from established structures controls the slow
      remodeling of crescentin in C. crescentus.

PMID- 20140234
TI  - Network-based elucidation of human disease similarities reveals common functional
      modules enriched for pluripotent drug targets.
AB  - Current work in elucidating relationships between diseases has largely been based
      on pre-existing knowledge of disease genes. Consequently, these studies are
      limited in their discovery of new and unknown disease relationships. We present
      the first quantitative framework to compare and contrast diseases by an
      integrated analysis of disease-related mRNA expression data and the human protein
      interaction network. We identified 4,620 functional modules in the human protein
      network and provided a quantitative metric to record their responses in 54
      diseases leading to 138 significant similarities between diseases. Fourteen of
      the significant disease correlations also shared common drugs, supporting the
      hypothesis that similar diseases can be treated by the same drugs, allowing us to
      make predictions for new uses of existing drugs. Finally, we also identified 59
      modules that were dysregulated in at least half of the diseases, representing a
      common disease-state "signature". These modules were significantly enriched for
      genes that are known to be drug targets. Interestingly, drugs known to target
      these genes/proteins are already known to treat significantly more diseases than
      drugs targeting other genes/proteins, highlighting the importance of these core
      modules as prime therapeutic opportunities.

PMID- 20140235
TI  - Fis is essential for capsule production in Pasteurella multocida and regulates
      expression of other important virulence factors.
AB  - P. multocida is the causative agent of a wide range of diseases of animals,
      including fowl cholera in poultry and wild birds. Fowl cholera isolates of P.
      multocida generally express a capsular polysaccharide composed of hyaluronic
      acid. There have been reports of spontaneous capsule loss in P. multocida, but
      the mechanism by which this occurs has not been determined. In this study, we
      identified three independent strains that had spontaneously lost the ability to
      produce capsular polysaccharide. Quantitative RT-PCR showed that these strains
      had significantly reduced transcription of the capsule biosynthetic genes, but
      DNA sequence analysis identified no mutations within the capsule biosynthetic
      locus. However, whole-genome sequencing of paired capsulated and acapsular
      strains identified a single point mutation within the fis gene in the acapsular
      strain. Sequencing of fis from two independently derived spontaneous acapsular
      strains showed that each contained a mutation within fis. Complementation of
      these strains with an intact copy of fis, predicted to encode a transcriptional
      regulator, returned capsule expression to all strains. Therefore, expression of a
      functional Fis protein is essential for capsule expression in P. multocida. DNA
      microarray analysis of one of the spontaneous fis mutants identified
      approximately 30 genes as down-regulated in the mutant, including pfhB_2, which
      encodes a filamentous hemagglutinin, a known P. multocida virulence factor, and
      plpE, which encodes the cross protective surface antigen PlpE. Therefore these
      experiments define for the first time a mechanism for spontaneous capsule loss in
      P. multocida and identify Fis as a critical regulator of capsule expression.
      Furthermore, Fis is involved in the regulation of a range of other P. multocida
      genes including important virulence factors.

PMID- 20140236
TI  - Wing patterns in the mist.

PMID- 20140237
TI  - DNA binding of centromere protein C (CENPC) is stabilized by single-stranded RNA.
AB  - Centromeres are the attachment points between the genome and the cytoskeleton:
      centromeres bind to kinetochores, which in turn bind to spindles and move
      chromosomes. Paradoxically, the DNA sequence of centromeres has little or no role
      in perpetuating kinetochores. As such they are striking examples of genetic
      information being transmitted in a manner that is independent of DNA sequence
      (epigenetically). It has been found that RNA transcribed from centromeres remains
      bound within the kinetochore region, and this local population of RNA is thought
      to be part of the epigenetic marking system. Here we carried out a genetic and
      biochemical study of maize CENPC, a key inner kinetochore protein. We show that
      DNA binding is conferred by a localized region 122 amino acids long, and that the
      DNA-binding reaction is exquisitely sensitive to single-stranded RNA. Long,
      single-stranded nucleic acids strongly promote the binding of CENPC to DNA, and
      the types of RNAs that stabilize DNA binding match in size and character the RNAs
      present on kinetochores in vivo. Removal or replacement of the binding module
      with HIV integrase binding domain causes a partial delocalization of CENPC in
      vivo. The data suggest that centromeric RNA helps to recruit CENPC to the inner
      kinetochore by altering its DNA binding characteristics.

PMID- 20140238
TI  - Human and non-human primate genomes share hotspots of positive selection.
AB  - Among primates, genome-wide analysis of recent positive selection is currently
      limited to the human species because it requires extensive sampling of genotypic
      data from many individuals. The extent to which genes positively selected in
      human also present adaptive changes in other primates therefore remains unknown.
      This question is important because a gene that has been positively selected
      independently in the human and in other primate lineages may be less likely to be
      involved in human specific phenotypic changes such as dietary habits or cognitive
      abilities. To answer this question, we analysed heterozygous Single Nucleotide
      Polymorphisms (SNPs) in the genomes of single human, chimpanzee, orangutan, and
      macaque individuals using a new method aiming to identify selective sweeps genome
      wide. We found an unexpectedly high number of orthologous genes exhibiting
      signatures of a selective sweep simultaneously in several primate species,
      suggesting the presence of hotspots of positive selection. A similar significant
      excess is evident when comparing genes positively selected during recent human
      evolution with genes subjected to positive selection in their coding sequence in
      other primate lineages and identified using a different test. These findings are
      further supported by comparing several published human genome scans for positive
      selection with our findings in non-human primate genomes. We thus provide
      extensive evidence that the co-occurrence of positive selection in humans and in
      other primates at the same genetic loci can be measured with only four species,
      an indication that it may be a widespread phenomenon. The identification of
      positive selection in humans alongside other primates is a powerful tool to
      outline those genes that were selected uniquely during recent human evolution.

PMID- 20140239
TI  - Genomic hotspots for adaptation: the population genetics of Mullerian mimicry in
      Heliconius erato.
AB  - Wing pattern evolution in Heliconius butterflies provides some of the most
      striking examples of adaptation by natural selection. The genes controlling
      pattern variation are classic examples of Mendelian loci of large effect, where
      allelic variation causes large and discrete phenotypic changes and is responsible
      for both convergent and highly divergent wing pattern evolution across the genus.
      We characterize nucleotide variation, genotype-by-phenotype associations, linkage
      disequilibrium (LD), and candidate gene expression patterns across two unlinked
      genomic intervals that control yellow and red wing pattern variation among
      mimetic forms of Heliconius erato. Despite very strong natural selection on color
      pattern, we see neither a strong reduction in genetic diversity nor evidence for
      extended LD across either patterning interval. This observation highlights the
      extent that recombination can erase the signature of selection in natural
      populations and is consistent with the hypothesis that either the adaptive
      radiation or the alleles controlling it are quite old. However, across both
      patterning intervals we identified SNPs clustered in several coding regions that
      were strongly associated with color pattern phenotype. Interestingly, coding
      regions with associated SNPs were widely separated, suggesting that color pattern
      alleles may be composed of multiple functional sites, conforming to previous
      descriptions of these loci as "supergenes." Examination of gene expression levels
      of genes flanking these regions in both H. erato and its co-mimic, H. melpomene,
      implicate a gene with high sequence similarity to a kinesin as playing a key role
      in modulating pattern and provides convincing evidence for parallel changes in
      gene regulation across co-mimetic lineages. The complex genetic architecture at
      these color pattern loci stands in marked contrast to the single casual mutations
      often identified in genetic studies of adaptation, but may be more indicative of
      the type of genetic changes responsible for much of the adaptive variation found
      in natural populations.

PMID- 20140240
TI  - Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3,
      cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial
      Rosai-Dorfman disease.
AB  - The histiocytoses are a heterogeneous group of disorders characterised by an
      excessive number of histiocytes. In most cases the pathophysiology is unclear and
      treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been
      classed as an autosomal recessively inherited form of histiocytosis with
      similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis
      with massive lymphadenopathy (SHML)). To elucidate the molecular basis of FHC, we
      performed autozygosity mapping studies in a large consanguineous family and
      identified a novel locus at chromosome 10q22.1. Mutation analysis of candidate
      genes within the target interval identified biallelic germline mutations in
      SLC29A3 in the FHC kindred and in two families reported to have familial RDD.
      Analysis of SLC29A3 expression during mouse embryogenesis revealed widespread
      expression by e14.5 with prominent expression in the central nervous system, eye,
      inner ear, and epithelial tissues including the gastrointestinal tract. SLC29A3
      encodes an intracellular equilibrative nucleoside transporter (hENT3) with
      affinity for adenosine. Recently germline mutations in SLC29A3 were also
      described in two rare autosomal recessive disorders with overlapping phenotypes:
      (a) H syndrome (MIM 612391) that is characterised by cutaneous hyperpigmentation
      and hypertrichosis, hepatomegaly, heart anomalies, hearing loss, and
      hypogonadism; and (b) PHID (pigmented hypertrichosis with insulin-dependent
      diabetes mellitus) syndrome. Our findings suggest that a variety of clinical
      diagnoses (H and PHID syndromes, FHC, and familial RDD) can be included in a new
      diagnostic category of SLC29A3 spectrum disorder.

PMID- 20140241
TI  - A universal trend of reduced mRNA stability near the translation-initiation site
      in prokaryotes and eukaryotes.
AB  - Recent studies have suggested that the thermodynamic stability of mRNA secondary
      structure near the start codon can regulate translation efficiency in Escherichia
      coli, and that translation is more efficient the less stable the secondary
      structure. We survey the complete genomes of 340 species for signals of reduced
      mRNA secondary structure near the start codon. Our analysis includes bacteria,
      archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly
      all species show evidence for reduced mRNA stability near the start codon. The
      reduction in stability generally increases with increasing genomic GC content. In
      prokaryotes, the reduction also increases with decreasing optimal growth
      temperature. Within genomes, there is variation in the stability among genes, and
      this variation correlates with gene GC content, codon bias, and gene expression
      level. For birds and mammals, however, we do not find a genome-wide trend of
      reduced mRNA stability near the start codon. Yet the most GC rich genes in these
      organisms do show such a signal. We conclude that reduced stability of the mRNA
      secondary structure near the start codon is a universal feature of all cellular
      life. We suggest that the origin of this reduction is selection for efficient
      recognition of the start codon by initiator-tRNA.

PMID- 20140242
TI  - Elevated cardiac troponin I in sepsis and septic shock: no evidence for thrombus
      associated myocardial necrosis.
AB  - BACKGROUND: Elevated cardiac troponin I (cTnI) is frequently observed in patients
      with severe sepsis and septic shock. However, the mechanisms underlying cTnI
      release in these patients are still unknown. To date no data regarding
      coagulation disturbances as a possible mechanism for cTnI release during sepsis
      are available. METHODOLOGY/PRINCIPAL FINDINGS: Consecutive patients with systemic
      inflammatory response syndrome (SIRS), sepsis or septic shock without evidence of
      an acute coronary syndrome were analyzed. Coagulation parameters (clotting time
      (CT), clot formation time (CFT), maximum clot firmness (MCF), alpha-angle) were
      assessed in native whole blood samples, and using specific activators to evaluate
      the extrinsic and intrinsic as well as the fibrin component of the coagulation
      pathway with the use of rotational thrombelastometry (ROTEM). Thirty-eight
      patients were included and 22 (58%) were cTnI-positive. Baseline characteristics
      between TnI-positive and -negative patients were similar. The CT, CFT, MCF and
      the alpha-angle were similar between the groups with trends towards shorter CT in
      the extrinsic and fibrin activation. CONCLUSIONS/SIGNIFICANCE: We found no
      differences in coagulation parameters analyzed with rotational thrombelastometry
      between cTnI-positive and -negative patients with SIRS, severe sepsis, and septic
      shock. These findings suggest that pathophysiological mechanisms other than
      thrombus-associated myocardial damage might play a major role, including
      reversible myocardial membrane leakage and/or cytokine mediated apoptosis in
      these patients.

PMID- 20140243
TI  - Genetically-defined deficiency of mannose-binding lectin is associated with
      protection after experimental stroke in mice and outcome in human stroke.
AB  - BACKGROUND: The complement system is a major effector of innate immunity that has
      been involved in stroke brain damage. Complement activation occurs through the
      classical, alternative and lectin pathways. The latter is initiated by mannose
      binding lectin (MBL) and MBL-associated serine proteases (MASPs). Here we
      investigated whether the lectin pathway contributes to stroke outcome in mice and
      humans. METHODOLOGY/PRINCIPAL FINDINGS: Focal cerebral ischemia/reperfusion in
      MBL-null mice induced smaller infarctions, better functional outcome, and
      diminished C3 deposition and neutrophil infiltration than in wild-type mice.
      Accordingly, reconstitution of MBL-null mice with recombinant human MBL (rhMBL)
      enhanced brain damage. In order to investigate the clinical relevance of these
      experimental observations, a study of MBL2 and MASP-2 gene polymorphism rendering
      the lectin pathway dysfunctional was performed in 135 stroke patients. In
      logistic regression adjusted for age, gender and initial stroke severity,
      unfavourable outcome at 3 months was associated with MBL-sufficient genotype (OR
      10.85, p = 0.008) and circulating MBL levels (OR 1.29, p = 0.04). Individuals
      carrying MBL-low genotypes (17.8%) had lower C3, C4, and CRP levels, and the
      proinflammatory cytokine profile was attenuated versus MBL-sufficient genotypes.
      CONCLUSIONS/SIGNIFICANCE: In conclusion, genetically defined MBL-deficiency is
      associated with a better outcome after acute stroke in mice and humans.

PMID- 20140244
TI  - Large direct repeats flank genomic rearrangements between a new clinical isolate
      of Francisella tularensis subsp. tularensis A1 and Schu S4.
AB  - Francisella tularensis subspecies tularensis consists of two separate populations
      A1 and A2. This report describes the complete genome sequence of NE061598, an F.
      tularensis subspecies tularensis A1 isolated in 1998 from a human with clinical
      disease in Nebraska, United States of America. The genome sequence was compared
      to Schu S4, an F. tularensis subspecies tularensis A1a strain originally isolated
      in Ohio in 1941. It was determined that there were 25 nucleotide polymorphisms
      (22 SNPs and 3 indels) between Schu S4 and NE061598; two of these polymorphisms
      were in potential virulence loci. Pulsed-field gel electrophoresis analysis
      demonstrated that NE061598 was an A1a genotype. Other differences included repeat
      sequences (n = 11 separate loci), four of which were contained in coding
      sequences, and an inversion and rearrangement probably mediated by insertion
      sequences and the previously identified direct repeats I, II, and III. Five new
      variable-number tandem repeats were identified; three of these five were unique
      in NE061598 compared to Schu S4. Importantly, there was no gene loss or gain
      identified between NE061598 and Schu S4. Interpretation of these data suggests
      there is significant sequence conservation and chromosomal synteny within the A1
      population. Further studies are needed to determine the biological properties
      driving the selective pressure that maintains the chromosomal structure of this
      monomorphic pathogen.

PMID- 20140245
TI  - Neurofilament heavy polypeptide regulates the Akt-beta-catenin pathway in human
      esophageal squamous cell carcinoma.
AB  - Aerobic glycolysis and mitochondrial dysfunction are common features of
      aggressive cancer growth. We observed promoter methylation and loss of expression
      in neurofilament heavy polypeptide (NEFH) in a significant proportion of primary
      esophageal squamous cell carcinoma (ESCC) samples that were of a high tumor grade
      and advanced stage. RNA interference-mediated knockdown of NEFH accelerated ESCC
      cell growth in culture and increased tumorigenicity in vivo, whereas forced
      expression of NEFH significantly inhibited cell growth and colony formation. Loss
      of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of
      pyruvate dehydrogenase, via activation of the Akt/beta-catenin pathway, resulting
      in enhanced aerobic glycolysis and mitochondrial dysfunction. The acceleration of
      glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed
      in the absence of beta-catenin expression, and was decreased by the treatment of
      2-Deoxyglucose, a glycolytic inhibitor, or API-2, an Akt inhibitor. Loss of NEFH
      activates the Akt/beta-catenin pathway and increases glycolysis and mitochondrial
      dysfunction. Cancer cells with methylated NEFH can be targeted for destruction
      with specific inhibitors of deregulated downstream pathways.

PMID- 20140246
TI  - Bilingualism accentuates children's conversational understanding.
AB  - BACKGROUND: Although bilingualism is prevalent throughout the world, little is
      known about the extent to which it influences children's conversational
      understanding. Our investigation involved children aged 3-6 years exposed to one
      or more of four major languages: English, German, Italian, and Japanese. In two
      experiments, we examined the children's ability to identify responses to
      questions as violations of conversational maxims (to be informative and avoid
      redundancy, to speak the truth, be relevant, and be polite). PRINCIPAL FINDINGS:
      In Experiment 1, with increasing age, children showed greater sensitivity to
      maxim violations. Children in Italy who were bilingual in German and Italian
      (with German as the dominant language L1) significantly outperformed Italian
      monolinguals. In Experiment 2, children in England who were bilingual in English
      and Japanese (with English as L1) significantly outperformed Japanese
      monolinguals in Japan with vocabulary age partialled out. CONCLUSIONS: As the
      monolingual and bilingual groups had a similar family SES background (Experiment
      1) and similar family cultural identity (Experiment 2), these results point to a
      specific role for early bilingualism in accentuating children's developing
      ability to appreciate effective communicative responses.

PMID- 20140247
TI  - Group hunting-a reason for sociality in molossid bats?
AB  - Many bat species live in groups, some of them in highly complex social systems,
      but the reasons for sociality in bats remain largely unresolved. Increased
      foraging efficiency through passive information transfer in species foraging for
      ephemeral insects has been postulated as a reason for group formation of male
      bats in the temperate zones. We hypothesized that benefits from group hunting
      might also entice tropical bats of both sexes to live in groups. Here we
      investigate whether Molossus molossus, a small insectivorous bat in Panama, hunts
      in groups. We use a phased antenna array setup to reduce error in telemetry
      bearings. Our results confirmed that simultaneously radiotracked individuals from
      the same colony foraged together significantly more than expected by chance. Our
      data are consistent with the hypothesis that many bats are social because of
      information transfer between foraging group members. We suggest this reason for
      sociality to be more widespread than currently assumed. Furthermore, benefits
      from group hunting may also have contributed to the evolution of group living in
      other animals specialized on ephemeral food sources.

PMID- 20140248
TI  - Increasing tPA activity in astrocytes induced by multipotent mesenchymal stromal
      cells facilitate neurite outgrowth after stroke in the mouse.
AB  - We demonstrate that tissue plasminogen activator (tPA) and its inhibitors
      contribute to neurite outgrowth in the central nervous system (CNS) after
      treatment of stroke with multipotent mesenchymal stromal cells (MSCs). In vivo,
      administration of MSCs to mice subjected to middle cerebral artery occlusion
      (MCAo) significantly increased activation of tPA and downregulated PAI-1 levels
      in the ischemic boundary zone (IBZ) compared with control PBS treated mice,
      concurrently with increases of myelinated axons and synaptophysin. In vitro, MSCs
      significantly increased tPA levels and concomitantly reduced plasminogen
      activator inhibitor 1 (PAI-1) expression in astrocytes under normal and oxygen
      and glucose deprivation (OGD) conditions. ELISA analysis of conditioned medium
      revealed that MSCs stimulated astrocytes to secrete tPA. When primary cortical
      neurons were cultured in the conditioned medium from MSC co-cultured astrocytes,
      these neurons exhibited a significant increase in neurite outgrowth compared to
      conditioned medium from astrocytes alone. Blockage of tPA with a neutralizing
      antibody or knock-down of tPA with siRNA significantly attenuated the effect of
      the conditioned medium on neurite outgrowth. Addition of recombinant human tPA
      into cortical neuronal cultures also substantially enhanced neurite outgrowth.
      Collectively, these in vivo and in vitro data suggest that the MSC mediated
      increased activation of tPA in astrocytes promotes neurite outgrowth after
      stroke.

PMID- 20140249
TI  - Structure and kinetic investigation of Streptococcus pyogenes family GH38 alpha
      mannosidase.
AB  - BACKGROUND: The enzymatic hydrolysis of alpha-mannosides is catalyzed by
      glycoside hydrolases (GH), termed alpha-mannosidases. These enzymes are found in
      different GH sequence-based families. Considerable research has probed the role
      of higher eukaryotic "GH38" alpha-mannosides that play a key role in the
      modification and diversification of hybrid N-glycans; processes with strong
      cellular links to cancer and autoimmune disease. The most extensively studied of
      these enzymes is the Drosophila GH38 alpha-mannosidase II, which has been shown
      to be a retaining alpha-mannosidase that targets both alpha-1,3 and alpha-1,6
      mannosyl linkages, an activity that enables the enzyme to process
      GlcNAc(Man)(5)(GlcNAc)(2) hybrid N-glycans to GlcNAc(Man)(3)(GlcNAc)(2). Far less
      well understood is the observation that many bacterial species, predominantly but
      not exclusively pathogens and symbionts, also possess putative GH38 alpha
      mannosidases whose activity and specificity is unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we show that the Streptococcus pyogenes (M1 GAS SF370) GH38 enzyme
      (Spy1604; hereafter SpGH38) is an alpha-mannosidase with specificity for alpha
      1,3 mannosidic linkages. The 3D X-ray structure of SpGH38, obtained in native
      form at 1.9 A resolution and in complex with the inhibitor swainsonine (K(i) 18
      microM) at 2.6 A, reveals a canonical GH38 five-domain structure in which the
      catalytic "-1" subsite shows high similarity with the Drosophila enzyme,
      including the catalytic Zn(2+) ion. In contrast, the "leaving group" subsites of
      SpGH38 display considerable differences to the higher eukaryotic GH38s; features
      that contribute to their apparent specificity. CONCLUSIONS/SIGNIFICANCE: Although
      the in vivo function of this streptococcal GH38 alpha-mannosidase remains
      unknown, it is shown to be an alpha-mannosidase active on N-glycans. SpGH38 lies
      on an operon that also contains the GH84 hexosaminidase (Spy1600) and an
      additional putative glycosidase. The activity of SpGH38, together with its
      genomic context, strongly hints at a function in the degradation of host N- or
      possibly O-glycans. The absence of any classical signal peptide further suggests
      that SpGH38 may be intracellular, perhaps functioning in the subsequent
      degradation of extracellular host glycans following their initial digestion by
      secreted glycosidases.

PMID- 20140250
TI  - Effect of a high intake of conjugated linoleic acid on lipoprotein levels in
      healthy human subjects.
AB  - BACKGROUND: Trans fatty acids are produced either by industrial hydrogenation or
      by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids
      lower high-density lipoprotein (HDL) cholesterol, raise low-density lipoprotein
      (LDL) cholesterol, and increase the risk of coronary heart disease. The effects
      of trans fatty acids from ruminants are less clear. We investigated the effect on
      blood lipids of cis-9, trans-11 conjugated linoleic acid (CLA), a trans fatty
      acid largely restricted to ruminant fats. METHODOLOGY/PRINCIPAL FINDINGS: Sixty
      one healthy women and men were sequentially fed each of three diets for three
      weeks, in random order, for a total of nine weeks. Diets were identical except
      for 7% of energy (approximately 20 g/day), which was provided either by oleic
      acid, by industrial trans fatty acids, or by a mixture of 80% cis-9, trans-11 and
      20% trans-10, cis-12 CLA. After the oleic acid diet, mean (+/- SD) serum LDL
      cholesterol was 2.68+/-0.62 mmol/L compared to 3.00+/-0.66 mmol/L after
      industrial trans fatty acids (p<0.001), and 2.92+/-0.70 mmol/L after CLA
      (p<0.001). Compared to oleic acid, HDL-cholesterol was 0.05+/-0.12 mmol/L lower
      after industrial trans fatty acids (p = 0.001) and 0.06+/-0.10 mmol/L lower after
      CLA (p<0.001). The total-to-HDL cholesterol ratio was 11.6% higher after
      industrial trans fatty acids (p<0.001) and 10.0% higher after CLA (p<0.001)
      relative to the oleic acid diet. CONCLUSIONS/SIGNIFICANCE: High intakes of an
      80:20 mixture of cis-9, trans-11 and trans-10, cis-12 CLA raise the total to HDL
      cholesterol ratio in healthy volunteers. The effect of CLA may be somewhat less
      than that of industrial trans fatty acids. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00529828.

PMID- 20140251
TI  - Single assay for simultaneous detection and differential identification of human
      and avian influenza virus types, subtypes, and emergent variants.
AB  - For more than four decades the cause of most type A influenza virus infections of
      humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In
      contrast, avian and other vertebrate species are a reservoir of type A influenza
      virus genome diversity, hosting strains representing at least 120 of 144
      combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral
      genome segment reassortments and mutations emerging within this reservoir may
      spawn new influenza virus strains as imminent epidemic or pandemic threats to
      human health and poultry production. Traditional methods to detect and
      differentiate influenza virus subtypes are either time-consuming and labor
      intensive (culture-based) or remarkably insensitive (antibody-based). Molecular
      diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT
      PCR) have short assay cycle time, and high analytical sensitivity and
      specificity. However, none of these diagnostic tests determine viral gene
      nucleotide sequences to distinguish strains and variants of a detected pathogen
      from one specimen to the next. Decision-quality, strain- and variant-specific
      pathogen gene sequence information may be critical for public health, infection
      control, surveillance, epidemiology, or medical/veterinary treatment planning.
      The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed
      and target gene sequencing-based alternative to both traditional culture- or
      biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential
      diagnostic assay for all subtype combinations of type A influenza viruses and for
      30 other viral and bacterial pathogens that may cause influenza-like illness.
      These other pathogen targets of RPM-Flu may co-infect and compound the morbidity
      and/or mortality of patients with influenza. The informative specificity of a
      single RPM-Flu test represents specimen-specific viral gene sequences as
      determinants of virus type, A/HN subtype, virulence, host-range, and resistance
      to antiviral agents.

PMID- 20140253
TI  - From dynamic live cell imaging to 3D ultrastructure: novel integrated methods for
      high pressure freezing and correlative light-electron microscopy.
AB  - BACKGROUND: In cell biology, the study of proteins and organelles requires the
      combination of different imaging approaches, from live recordings with light
      microscopy (LM) to electron microscopy (EM). METHODOLOGY: To correlate dynamic
      events in adherent cells with both ultrastructural and 3D information, we
      developed a method for cultured cells that combines confocal time-lapse images of
      GFP-tagged proteins with electron microscopy. With laser micro-patterned culture
      substrate, we created coordinates that were conserved at every step of the sample
      preparation and visualization processes. Specifically designed for cryo-fixation,
      this method allowed a fast freezing of dynamic events within seconds and their
      ultrastructural characterization. We provide examples of the dynamic
      oligomerization of GFP-tagged myotubularin (MTM1) phosphoinositides phosphatase
      induced by osmotic stress, and of the ultrastructure of membrane tubules
      dependent on amphiphysin 2 (BIN1) expression. CONCLUSION: Accessible and
      versatile, we show that this approach is efficient to routinely correlate
      functional and dynamic LM with high resolution morphology by EM, with immuno-EM
      labeling, with 3D reconstruction using serial immuno-EM or tomography, and with
      scanning-EM.

PMID- 20140252
TI  - Complete-proteome mapping of human influenza A adaptive mutations: implications
      for human transmissibility of zoonotic strains.
AB  - BACKGROUND: There is widespread concern that H5N1 avian influenza A viruses will
      emerge as a pandemic threat, if they become capable of human-to-human (H2H)
      transmission. Avian strains lack this capability, which suggests that it requires
      important adaptive mutations. We performed a large-scale comparative analysis of
      proteins from avian and human strains, to produce a catalogue of mutations
      associated with H2H transmissibility, and to detect their presence in avian
      isolates. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a dataset of influenza A
      protein sequences from 92,343 public database records. Human and avian sequence
      subsets were compared, using a method based on mutual information, to identify
      characteristic sites where human isolates present conserved mutations. The
      resulting catalogue comprises 68 characteristic sites in eight internal proteins.
      Subtype variability prevented the identification of adaptive mutations in the
      hemagglutinin and neuraminidase proteins. The high number of sites in the
      ribonucleoprotein complex suggests interdependence between mutations in multiple
      proteins. Characteristic sites are often clustered within known functional
      regions, suggesting their functional roles in cellular processes. By isolating
      and concatenating characteristic site residues, we defined adaptation signatures,
      which summarize the adaptive potential of specific isolates. Most adaptive
      mutations emerged within three decades after the 1918 pandemic, and have remained
      remarkably stable thereafter. Two lineages with stable internal protein
      constellations have circulated among humans without reassorting. On the contrary,
      H5N1 avian and swine viruses reassort frequently, causing both gains and losses
      of adaptive mutations. CONCLUSIONS: Human host adaptation appears to be complex
      and systemic, involving nearly all influenza proteins. Adaptation signatures
      suggest that the ability of H5N1 strains to infect humans is related to the
      presence of an unusually high number of adaptive mutations. However, these
      mutations appear unstable, suggesting low pandemic potential of H5N1 in its
      current form. In addition, adaptation signatures indicate that pandemic H1N1/09
      strain possesses multiple human-transmissibility mutations, though not an
      unusually high number with respect to swine strains that infected humans in the
      past. Adaptation signatures provide a novel tool for identifying zoonotic strains
      with the potential to infect humans.

PMID- 20140254
TI  - High-precision radiosurgical dose delivery by interlaced microbeam arrays of high
      flux low-energy synchrotron X-rays.
AB  - Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated
      to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray
      beams on the basis of spatial beam fractionation. Due to the radioresistance of
      normal brain vasculature to MRT, a continuous blood supply can be maintained
      which would in part explain the surprising tolerance of normal tissues to very
      high radiation doses (hundreds of Gy). Based on this well described normal tissue
      sparing effect of microplanar beams, we developed a new irradiation geometry
      which allows the delivery of a high uniform dose deposition at a given brain
      target whereas surrounding normal tissues are irradiated by well tolerated
      parallel microbeams only. Normal rat brains were exposed to 4 focally interlaced
      arrays of 10 microplanar beams (52 microm wide, spaced 200 microm on-center, 50
      to 350 keV in energy range), targeted from 4 different ports, with a peak
      entrance dose of 200Gy each, to deliver an homogenous dose to a target volume of
      7 mm(3) in the caudate nucleus. Magnetic resonance imaging follow-up of rats
      showed a highly localized increase in blood vessel permeability, starting 1 week
      after irradiation. Contrast agent diffusion was confined to the target volume and
      was still observed 1 month after irradiation, along with histopathological
      changes, including damaged blood vessels. No changes in vessel permeability were
      detected in the normal brain tissue surrounding the target. The interlacing
      radiation-induced reduction of spontaneous seizures of epileptic rats illustrated
      the potential pre-clinical applications of this new irradiation geometry.
      Finally, Monte Carlo simulations performed on a human-sized head phantom
      suggested that synchrotron photons can be used for human radiosurgical
      applications. Our data show that interlaced microbeam irradiation allows a high
      homogeneous dose deposition in a brain target and leads to a confined tissue
      necrosis while sparing surrounding tissues. The use of synchrotron-generated X
      rays enables delivery of high doses for destruction of small focal regions in
      human brains, with sharper dose fall-offs than those described in any other
      conventional radiation therapy.

PMID- 20140255
TI  - Lack of sik1 in mouse embryonic stem cells impairs cardiomyogenesis by down
      regulating the cyclin-dependent kinase inhibitor p57kip2.
AB  - Sik1 (salt inducible kinase 1) is a serine/threonine kinase that belongs to the
      stress- and energy-sensing AMP-activated protein kinase family. During murine
      embryogenesis, sik1 marks the monolayer of future myocardial cells that will
      populate first the primitive ventricle, and later the primitive atrium suggesting
      its involvement in cardiac cell differentiation and/or heart development. Despite
      that observation, the involvement of sik1 in cardiac differentiation is still
      unknown. We examined the sik1 function during cardiomyocyte differentiation using
      the ES-derived embryoid bodies. We produced a null embryonic stem cell using a
      gene-trap cell line carrying an insertion in the sik1 locus. In absence of the
      sik1 protein, the temporal appearance of cardiomyocytes is delayed. Expression
      profile analysis revealed sik1 as part of a genetic network that controls the
      cell cycle, where the cyclin-dependent kinase inhibitor p57(Kip2) is directly
      involved. Collectively, we provided evidence that sik1-mediated effects are
      specific for cardiomyogenesis regulating cardiomyoblast cell cycle exit toward
      terminal differentiation.

PMID- 20140256
TI  - Primary metabolism of chickpea is the initial target of wound inducing early
      sensed Fusarium oxysporum f. sp. ciceri race I.
AB  - BACKGROUND: Biotrophic interaction between host and pathogen induces generation
      of reactive oxygen species that leads to programmed cell death of the host tissue
      specifically encompassing the site of infection conferring resistance to the
      host. However, in the present study, biotrophic relationship between Fusarium
      oxysporum and chickpea provided some novel insights into the classical concepts
      of defense signaling and disease perception where ROS (reactive oxygen species)
      generation followed by hypersensitive responses determined the magnitude of
      susceptibility or resistant potentiality of the host. METHODOLOGY/PRINCIPAL
      FINDINGS: Microscopic observations detected wound mediated in planta pathogenic
      establishment and its gradual progression within the host vascular tissue. cDNA
      AFLP showed differential expression of many defense responsive elements. Real
      time expression profiling also validated the early recognition of the wound
      inducing pathogen by the host. The interplay between fungus and host activated
      changes in primary metabolism, which generated defense signals in the form of
      sugar molecules for combating pathogenic encounter. CONCLUSIONS/SIGNIFICANCE: The
      present study showed the limitations of hypersensitive response mediated
      resistance, especially when foreign encounters involved the food production as
      well as the translocation machinery of the host. It was also predicted from the
      obtained results that hypersensitivity and active species generation failed to
      impart host defense in compatible interaction between chickpea and Fusarium. On
      the contrary, the defense related gene(s) played a critical role in conferring
      natural resistance to the resistant host. Thus, this study suggests that natural
      selection is the decisive factor for selecting and segregating out the suitable
      type of defense mechanism to be undertaken by the host without disturbing its
      normal metabolism, which could deviate from the known classical defense
      mechanisms.

PMID- 20140257
TI  - Effects of caller characteristics on auditory laterality in an early primate
      (Microcebus murinus).
AB  - BACKGROUND: Auditory laterality is suggested to be characterized by a left
      hemisphere dominance for the processing of conspecific communication.
      Nevertheless, there are indications that auditory laterality can also be affected
      by communicative significance, emotional valence and social recognition.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to gain insight into the effects of
      caller characteristics on auditory laterality in the early primate brain, 17 gray
      mouse lemurs were tested in a head turn paradigm. The head turn paradigm was
      established to examine potential functional hemispheric asymmetries on the
      behavioral level. Subjects were presented with playbacks of two conspecific call
      types (tsak calls and trill calls) from senders differing in familiarity
      (unfamiliar vs. familiar) and sex (same sex vs. other sex). Based on the head
      turn direction towards these calls, evidence was found for a right ear/left
      hemisphere dominance for the processing of calls of the other sex (Binomial test:
      p = 0.021, N = 10). Familiarity had no effect on the orientation biases.
      CONCLUSIONS/SIGNIFICANCE: The findings in this study support the growing
      consensus that auditory laterality is not only determined by the acoustic
      processing of conspecific communication, but also by other factors like the sex
      of the sender.

PMID- 20140258
TI  - Contribution of genome-wide HCV genetic differences to outcome of interferon
      based therapy in Caucasian American and African American patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) has six major genotypes, and patients
      infected with genotype 1 respond less well to interferon-based therapy than other
      genotypes. African American patients respond to interferon alpha-based therapy at
      about half the rate of Caucasian Americans. The effect of HCV's genetic variation
      on treatment outcome in both racial groups is poorly understood. METHODOLOGY: We
      determined the near full-length pre-therapy consensus sequences from 94 patients
      infected with HCV genotype 1a or 1b undergoing treatment with peginterferon alpha
      2a and ribavirin through the Virahep-C study. The sequences were stratified by
      genotype, race and treatment outcome to identify HCV genetic differences
      associated with treatment efficacy. PRINCIPAL FINDINGS: HCV sequences from
      patients who achieved sustained viral response were more diverse than sequences
      from non-responders. These inter-patient diversity differences were found
      primarily in the NS5A gene in genotype 1a and in core and NS2 in genotype 1b.
      These differences could not be explained by host selection pressures. Genotype 1b
      but not 1a African American patients had viral genetic differences that
      correlated with treatment outcome. CONCLUSIONS & SIGNIFICANCE: Higher inter
      patient viral genetic diversity correlated with successful treatment, implying
      that there are HCV genotype 1 strains with intrinsic differences in sensitivity
      to therapy. Core, NS3 and NS5A have interferon-suppressive activities detectable
      through in vitro assays, and hence these activities also appear to function in
      human patients. Both preferential infection with relatively resistant HCV
      variants and host-specific factors appear to contribute to the unusually poor
      response to therapy in African American patients.

PMID- 20140259
TI  - Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and
      enhance cytotoxic response against human melanoma cells.
AB  - BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due
      to the defective expression of class I major histocompatibility antigens (MHC-I)
      and costimulatory molecules. We have previously shown that geranylgeranyl
      transferase inhibition (done with GGTI-298) stimulates anti-melanoma immune
      response through MHC-I and costimulatory molecule expression in the B16F10 murine
      model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that
      vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection
      against untreated tumor growth and pulmonary metastases implantation.
      Furthermore, using a human melanoma model (LB1319-MEL), we demonstrated that in
      vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I
      and a costimulatory molecule CD86 and down regulation of an inhibitory molecule
      PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC)
      revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected
      melanoma cells, enables the stimulation of lymphocytes from HLA compatible
      healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment
      with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient
      at inducing the: i) activation of CD8 T lymphocytes (CD8+/CD69+); ii)
      proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+); iii) secretion
      of hIFN-gamma; and iv) anti-melanoma specific cytotoxic cells.
      CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of
      melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity
      and could be a novel approach to produce tumor cells suitable for vaccination and
      for stimulation of anti-melanoma effector cells.

PMID- 20140260
TI  - Does parenteral nutrition influence electrolyte and fluid balance in preterm
      infants in the first days after birth?
AB  - BACKGROUND: New national guidelines recommend more restricted fluid intake and
      early initiation of total parenteral nutrition (TPN) in very preterm infants. The
      aim was study the effect of these guidelines on serum sodium and potassium levels
      and fluid balance in the first three days after birth. METHODS: Two cohorts of
      infants <28 weeks gestational age, born at the Leiden University Medical Center
      in the Netherlands, were compared retrospectively before (2002-2004, late-TPN)
      and after (2006-2007, early-TPN) introduction of the new Dutch guideline. Outcome
      measures were serum sodium and potassium levels, diuresis, and changes in body
      weight in the first three postnatal days. RESULTS: In the first three postnatal
      days no differences between late-TPN (N = 70) and early-TPN cohort (N = 73) in
      mean (SD) serum sodium (141.1 (3.8) vs 141.0 (3.7) mmol/l) or potassium (4.3
      (0.5) vs 4.3 (0.5) mmol/l) were found, but in the early-TPN cohort diuresis (4.5
      (1.6) vs 3.2 (1.4) ml/kg/h) and loss of body weight were decreased (-6.0% (7.7)
      vs -0.8% (8.0)). CONCLUSIONS: Initiation of TPN immediately after birth and
      restricted fluid intake in very preterm infants do not seem to influence serum
      sodium and potassium levels in first three postnatal days. Further research is
      needed to see if a decreased diuresis and loss of body weight in the first days
      is the result of a delayed postnatal adaptation or better energy balance.

PMID- 20140261
TI  - Genes confer similar robustness to environmental, stochastic, and genetic
      perturbations in yeast.
AB  - Gene inactivation often has little or no apparent consequence for the phenotype
      of an organism. This property-enetic (or mutational) robustness-is pervasive, and
      has important implications for disease and evolution, but is not well understood.
      Dating back to at least Waddington, it has been suggested that mutational
      robustness may be related to the requirement to withstand environmental or
      stochastic perturbations. Here I show that global quantitative data from yeast
      are largely consistent with this idea. Considering the effects of mutations in
      all nonessential genes shows that genes that confer robustness to environmental
      or stochastic change also buffer the effects of genetic change, and with similar
      efficacy. This means that selection during evolution for environmental or
      stochastic robustness (also referred to as canalization) may frequently have the
      side effect of increasing genetic robustness. A dynamic environment may therefore
      promote the evolution of phenotypic complexity. It also means that "hub" genes in
      genetic interaction (synthetic lethal) networks are generally genes that confer
      environmental resilience and phenotypic stability.

PMID- 20140262
TI  - Maternal and fetal genetic associations of PTGER3 and PON1 with preterm birth.
AB  - OBJECTIVE: The purpose of this study was to identify associations between
      maternal and fetal genetic variants in candidate genes and spontaneous preterm
      birth (PTB) in a Norwegian population and to determine the effect size of those
      associations that corroborate a previous study of PTB. METHODS: DNA from 434
      mother-baby dyads (214 cases and 220 controls) collected from the Norwegian
      Mother and Child Cohort (MoBa) was examined for association between 1,430 single
      nucleotide polymorphisms in 143 genes and PTB. These results were compared to a
      previous study on European Americans (EA) from Centennial Women's Hospital in
      Nashville, TN, USA. Odds ratios for SNPs that corroborated the Cenntennial study
      were determined on the combined MoBa and Centennial studies. RESULTS: In maternal
      samples the strongest results that corroborated the Centennial study were in the
      prostaglandin E receptor 3 gene (PTGER3; rs977214) (combined genotype p = 3x10(
      4)). The best model for rs977214 was the AG/GG genotypes relative to the AA
      genotype and resulted in an OR of 0.55 (95% CI = 0.37-0.82, p = 0.003),
      indicating a protective effect. In fetal samples the most significant association
      in the combined data was rs854552 in the paraoxonase 1 gene (PON1) (combined
      allele p = 8x10(-4)). The best model was the TT genotype relative to the CC/CT
      genotypes, and resulted in an OR of 1.32 (95% CI = 1.13-1.53, p = 4x10(-4)).
      CONCLUSIONS: These studies identify single locus associations with preterm birth
      for both maternal and fetal genotypes in two populations of European ancestry.

PMID- 20140263
TI  - Only slight impact of predicted replicative capacity for therapy response
      prediction.
AB  - BACKGROUND: Replication capacity (RC) of specific HIV isolates is occasionally
      blamed for unexpected treatment responses. However, the role of viral RC in
      response to antiretroviral therapy is not yet fully understood. MATERIALS AND
      METHODS: We developed a method for predicting RC from genotype using support
      vector machines (SVMs) trained on about 300 genotype-RC pairs. Next, we studied
      the impact of predicted viral RC (pRC) on the change of viral load (VL) and
      CD4(+) T-cell count (CD4) during the course of therapy on about 3,000 treatment
      change episodes (TCEs) extracted from the EuResist integrated database.
      Specifically, linear regression models using either treatment activity scores
      (TAS), the drug combination, or pRC or any combination of these covariates were
      trained to predict change in VL and CD4, respectively. RESULTS: The SVM models
      achieved a Spearman correlation (rho) of 0.54 between measured RC and pRC. The
      prediction of change in VL (CD4) was best at 180 (360) days, reaching a
      correlation of rho = 0.45 (rho = 0.27). In general, pRC was inversely correlated
      to drug resistance at treatment start (on average rho = -0.38). Inclusion of pRC
      in the linear regression models significantly improved prediction of virological
      response to treatment based either on the drug combination or on the TAS (t-test;
      p-values range from 0.0247 to 4 10(-6)) but not for the model using both TAS and
      drug combination. For predicting the change in CD4 the improvement derived from
      inclusion of pRC was not significant. CONCLUSION: Viral RC could be predicted
      from genotype with moderate accuracy and could slightly improve prediction of
      virological treatment response. However, the observed improvement could simply be
      a consequence of the significant correlation between pRC and drug resistance.

PMID- 20140264
TI  - Multiple origins of elytral reticulation modifications in the west palearctic
      Agabus bipustulatus complex (coleoptera, dytiscidae).
AB  - The Agabus bipustulatus complex includes one of Europe's most widely distributed
      and common diving beetles. This complex, which is known for its large
      morphological variation, has a complex demographic and altitudinal variation in
      elytral reticulation. The various depth of the reticulation imprint, both in
      smaller and larger meshes, results in both mat and shiny individuals, as well as
      intermediate forms. The West Palearctic lowland is inhabited by a sexually
      dimorphic form, with shiny males and mat females. In mountain regions, shiny
      individuals of both sexes are found intermixed with mat individuals or in pure
      populations in central and southern areas, whereas pure populations of mat
      individuals are exclusively found in the northern region at high altitude. Sexual
      selection is proposed as a driving force in shaping this variation. However, the
      occurrence of different types of reticulation in both sexes and disjunct
      geographical distribution patterns suggest an additional function of the
      reticulation. Here we investigate the phylogeographical history, genetic
      structure and reticulation variation of several named forms within the Agabus
      bipustulatus complex including A. nevadensis. The molecular analyses recognised
      several well-supported clades within the complex. Several of the named forms had
      two or more independent origins. Few south European populations were uniform in
      reticulation patterns, and the males were found to display large variation.
      Reticulation diversity and population genetic variability were clearly correlated
      to altitude, but no genetic differences were detected among populations with
      mixed or homogenous forms. Observed reduction in secondary reticulation in female
      and increased variance in male at high altitude in South Europe may be explained
      by the occurrence of an additional selective force, beside sexual selection. The
      combined effect of these selective processes is here demonstrated in an extreme
      case to generate isolation barriers between populations at high altitudes. Here
      we discuss this selective force in relation to thermal selection.

PMID- 20140265
TI  - Visualizing neuronal network connectivity with connectivity pattern tables.
AB  - Complex ideas are best conveyed through well-designed illustrations. Up to now,
      computational neuroscientists have mostly relied on box-and-arrow diagrams of
      even complex neuronal networks, often using ad hoc notations with conflicting use
      of symbols from paper to paper. This significantly impedes the communication of
      ideas in neuronal network modeling. We present here Connectivity Pattern Tables
      (CPTs) as a clutter-free visualization of connectivity in large neuronal networks
      containing two-dimensional populations of neurons. CPTs can be generated
      automatically from the same script code used to create the actual network in the
      NEST simulator. Through aggregation, CPTs can be viewed at different levels,
      providing either full detail or summary information. We also provide the open
      source ConnPlotter tool as a means to create connectivity pattern tables.

PMID- 20140266
TI  - Neurophysiological Distinction between Schizophrenia and Schizoaffective
      Disorder.
AB  - Schizoaffective disorder (SA) is distinguished from schizophrenia (SZ) based on
      the presence of prominent mood symptoms over the illness course. Despite this
      clinical distinction, SA and SZ patients are often combined in research studies,
      in part because data supporting a distinct pathophysiological boundary between
      the disorders are lacking. Indeed, few studies have addressed whether
      neurobiological abnormalities associated with SZ, such as the widely replicated
      reduction and delay of the P300 event-related potential (ERP), are also present
      in SA. Scalp EEG was acquired from patients with DSM-IV SA (n = 15) or SZ (n =
      22), as well as healthy controls (HC; n = 22) to assess the P300 elicited by
      infrequent target (15%) and task-irrelevant distractor (15%) stimuli in separate
      auditory and visual "oddball" tasks. P300 amplitude was reduced and delayed in
      SZ, relative to HC, consistent with prior studies. These SZ abnormalities did not
      interact with stimulus type (target vs. task-irrelevant distractor) or modality
      (auditory vs. visual). Across sensory modality and stimulus type, SA patients
      exhibited normal P300 amplitudes (significantly larger than SZ patients and
      indistinguishable from HC). However, P300 latency and reaction time were both
      equivalently delayed in SZ and SA patients, relative to HC. P300 differences
      between SA and SZ patients could not be accounted for by variation in symptom
      severity, socio-economic status, education, or illness duration. Although both
      groups show similar deficits in processing speed, SA patients do not exhibit the
      P300 amplitude deficits evident in SZ, consistent with an underlying
      pathophysiological boundary between these disorders.

PMID- 20140267
TI  - Novelty encoding by the output neurons of the Basal Ganglia.
AB  - Reinforcement learning models of the basal ganglia have focused on the
      resemblance of the dopamine signal to the temporal difference error. However the
      role of the network as a whole is still elusive, in particular whether the output
      of the basal ganglia encodes only the behavior (actions) or it is part of the
      valuation process. We trained a monkey extensively on a probabilistic conditional
      task with seven fractal cues predicting rewarding or aversive outcomes (familiar
      cues). Then in each recording session we added a cue that the monkey had never
      seen before (new cue) and recorded from single units in the Substantia Nigra pars
      reticulata (SNpr) while the monkey was engaged in a task with new cues
      intermingled within the familiar ones. The monkey learned the association between
      the new cue and outcome and modified its licking and blinking behavior which
      became similar to responses to the familiar cues with the same outcome. However,
      the responses of many SNpr neurons to the new cue exceeded their response to
      familiar cues even after behavioral learning was completed. This dissociation
      between behavior and neural activity suggests that the BG output code goes beyond
      instruction or gating of behavior to encoding of novel cues. Thus, BG output can
      enable learning at the levels of its target neural networks.

PMID- 20140268
TI  - Better than expected or as bad as you thought? The neurocognitive development of
      probabilistic feedback processing.
AB  - Learning from feedback lies at the foundation of adaptive behavior. Two prior
      neuroimaging studies have suggested that there are qualitative differences in how
      children and adults use feedback by demonstrating that dorsolateral prefrontal
      cortex (DLPFC) and parietal cortex were more active after negative feedback for
      adults, but after positive feedback for children. In the current study we used
      functional magnetic resonance imaging (fMRI) to test whether this difference is
      related to valence or informative value of the feedback by examining neural
      responses to negative and positive feedback while applying probabilistic rules.
      In total, 67 healthy volunteers between ages 8 and 22 participated in the study
      (8-11 years, n = 18; 13-16 years, n = 27; 18-22 years, n = 22). Behavioral
      comparisons showed that all participants were able to learn probabilistic rules
      equally well. DLPFC and dorsal anterior cingulate cortex were more active in
      younger children following positive feedback and in adults following negative
      feedback, but only when exploring alternative rules, not when applying the most
      advantageous rules. These findings suggest that developmental differences in
      neural responses to feedback are not related to valence per se, but that there is
      an age-related change in processing learning signals with different informative
      value.

PMID- 20140269
TI  - Knowledge-Driven Contrast Gain Control is Characterized by Two Distinct
      Electrocortical Markers.
AB  - Sensitivity to variations in luminance (contrast) is fundamental to perception
      because contrasts define the edges and textures of visual objects. Recent
      research has shown that contrast sensitivity, in addition to being controlled by
      purely stimulus-driven mechanisms, is also affected by expectations and prior
      knowledge about the contrast of upcoming stimuli. The ability to adjust contrast
      sensitivity based on expectations and prior knowledge could help to maximize the
      information extracted when scanning familiar visual scenes. In the present study
      we used the event-related potentials (ERP) technique to resolve the stages that
      mediate knowledge-driven aspects of contrast gain control. Using groupwise
      independent components analysis and multivariate partial least squares, we
      isolated two robust spatiotemporal patterns of electrical brain activity
      associated with preparation for upcoming targets whose contrast was predicted by
      a cue. The patterns were sensitive to the informative value of the cue. When the
      cues were informative, these patterns were also able to differentiate among cues
      that predicted low-contrast targets and cues that predicted high-contrast
      targets. Both patterns were localized to parts of occipitotemporal cortex, and
      their morphology, latency, and topography resembled P2/N2 and P3 potentials.
      These two patterns provide electrophysiological markers of knowledge-driven
      preparation for impending changes in contrast and shed new light on the manner in
      which top-down factors modulate sensory processing.

PMID- 20140270
TI  - Electrophysiological correlates of learning-induced modulation of visual motion
      processing in humans.
AB  - Training on a visual task leads to increased perceptual and neural responses to
      visual features that were attended during training as well as decreased responses
      to neglected distractor features. However, the time course of these attention
      based modulations of neural sensitivity for visual features has not been
      investigated before. Here we measured event related potentials (ERP) in response
      to motion stimuli with different coherence levels before and after training on a
      speed discrimination task requiring object-based attentional selection of one of
      the two competing motion stimuli. We found that two peaks on the ERP waveform
      were modulated by the strength of the coherent motion signal; the response
      amplitude associated with motion directions that were neglected during training
      was smaller than the response amplitude associated with motion directions that
      were attended during training. The first peak of motion coherence-dependent
      modulation of the ERP responses was at 300 ms after stimulus onset and it was
      most pronounced over the occipitotemporal cortex. The second peak was around 500
      ms and was focused over the parietal cortex. A control experiment suggests that
      the earlier motion coherence-related response modulation reflects the extraction
      of the coherent motion signal whereas the later peak might index accumulation and
      readout of motion signals by parietal decision mechanisms. These findings suggest
      that attention-based learning affects neural responses both at the sensory and
      decision processing stages.

PMID- 20140271
TI  - Cognitive function in early onset schizophrenia: a selective review.
AB  - Schizophrenia is widely regarded as the clinical outcome of aberrant
      neurodevelopment caused by a combination of genetic and non-genetic factors.
      Early Onset Schizophrenia (EOS) manifests in childhood or adolescence and
      represents a more severe variant of the Adult Onset form of the disorder (AOS).
      EOS offers a unique opportunity of exploring the impact of disease related
      mechanisms on the developmental trajectory of cognitive function. The present
      review focused on the domains of general intellectual ability (IQ), attention,
      executive function and memory. Significant methodological variability was noted
      across the different studies that examined these aspects of cognition in EOS
      patients. Despite this, a consistent pattern emergent from the data suggesting
      that (a) EOS patients compared to healthy children and adolescents show
      impairments of medium to large effect size in IQ, attention, memory and executive
      function (b) despite increased clinical severity, the cognitive profile of EOS
      patients is comparable to that of AOS patients (c) healthy adolescents show age
      related improvement in their ability to perform tests of attention, memory and
      executive function; this is not present in EOS patients thus resulting in
      increased age-related deviance in patients' performance. This apparent decline is
      mostly attributable to patients' failure to acquire new information and to use
      more sophisticated cognitive strategies.

PMID- 20140272
TI  - High glucose inhibits gene expression of tyrosyl-tRNA synthetase in osteoblast
      cells.
AB  - It has been suggested that bone metabolism disorders are one of the major
      complications of diabetes mellitus. However, the exact mechanisms as to how
      diabetes affects bone metabolism are yet to be determined. In the present study,
      we have searched for high glucose regulated genes in osteoblast-like UMR-106
      cells. UMR-106 cells were treated with normal glucose (5.5 mM), high glucose
      (16.5 mM or 30.5 mM) and mannitol (16.5 mM) as a hyperosmotic control. Following
      the isolation of total RNA, GeneFishing differential display-PCR (DDPCR) was
      carried out and followed by cloning, sequencing and searching in a gene bank data
      base to identify the high glucose induced gene(s). Through the DD-PCR technique
      which employs Annealing Control Primer, or ACP, it has been found that expression
      of a PCR product was significantly decreased by high glucose treatment: it was
      identified as tyrosyl-tRNA synthetase. Furthermore, reverse transcriptase PCR
      analysis confirmed that high glucose significantly decreases mRNA expression of
      tyrosyl-tRNA synthetase, whereas mannitol treatment does not cause any change in
      such expression. These results suggest that high glucose may play a significant
      role in the protein synthesis process of osteoblast cells by decreasing
      expression of tyrosyl-tRNA synthetase. In a Western blot analysis, the protein
      expression of tyrosyl-tRNA synthetase was also decreased by high glucose
      treatment. Taken together, these results suggest that high glucose could affect
      bone metabolism by regulating the expression of tyrosyl-tRNA synthetase genes.

PMID- 20140273
TI  - Antipyretic and antinociceptive properties of Mentha longifolia Huds. (Lamiaceae)
      leaf aqueous extract in rats and mice.
AB  - The antipyretic and antinociceptive properties of Mentha longifolia Huds.
      (Lamiaceae) leaf aqueous extract were investigated using lipopolysaccharide (LPS)
      induced pyrexia in rats, and acetic acid and hot plate analgesia tests in mice.
      Pentoxifylline, paracetamol and morphine were used as standard drugs for
      comparison. M. longifolia leaf aqueous extract and pentoxifylline (37.5-150 mg/kg
      i.p.) significantly (P < 0.05-0.02) reduced the LPS (50 g/kg i.m.)-elicited
      pyrexia. Pentoxifylline (50 mg/kg i.p.) also significantly (P < 0.01) reduced LPS
      (50 g/kg i.m.)-induced pyrexia. M. longifolia leaf aqueous extract (6.25-100
      mg/kg i.p.) and paracetamol (500 mg/kg i.p.) profoundly inhibited the writhes
      produced by 3% acetic acid. Furthermore, the plant extract (25-400 mg/kg i.p.)
      and morphine (10 mg/kg i.p.) significantly (P < 0.001) delayed the hot plate
      reaction time in mice. The LD(50) values for oral and intraperitoneal
      administration of the plant extract were > 3200 mg/kg and 1730 mg/kg,
      respectively. Phytochemical analysis revealed the presence of flavonoids,
      saponins, tannins, reducing sugars, cardiac glycosides and triterpene steroids in
      the leaves of M. longifolia. These data indicate that M. longifolia leaf aqueous
      extract has antipyretic and antinociceptive properties. Furthermore, the
      relatively high LD(50) values obtained for oral and intraperitoneal
      administration of the plant extract demonstrate that the plant extract is non
      toxic to mice.

PMID- 20140274
TI  - Anxiolytic-like effect of Aronia melanocarpa fruit juice in rats.
AB  - The main biologically active constituents of Aronia melanocarpa fruit juice
      (AMFJ) are polyphenolics, amongst them flavonoids, mainly anthocyanins. The aim
      of the present study was to investigate the effects of AMFJ (5 and 10 mL/kg) on
      anxiety using the social interaction test, on locomotor activity in the open
      field test and on working memory in the object recognition test in rats. AMFJ
      showed an anxiolytic-like effect which was demonstrated by a dose-dependent
      increase in the time of active social contacts between the test partners. The
      effects of both AMFJ doses were comparable to the effect of diazepam (1 mg/kg).
      AMFJ neither changed significantly horizontal and vertical locomotor activity,
      nor did it adversely affect working memory.

PMID- 20140275
TI  - Effects of a proprietary Bacillus coagulans preparation on symptoms of diarrhea
      predominant irritable bowel syndrome.
AB  - Symptoms of irritable bowel syndrome (IBS) have a profound impact on quality of
      life for many patients and current treatments are sometimes unsatisfactory. This
      controlled pilot study was conducted to evaluate effects of the proprietary
      GanedenBC(30) (Bacillus coagulans GBI-30, 6086) probiotic on IBS symptoms, in a
      randomized, double-blind, placebo-controlled clinical trial including patients
      with diarrhea-predominant IBS (IBS-D). Patients were randomized to receive either
      B. coagulans GBI-30, 6086 or placebo once a day for 8 weeks. Patients filled out
      a quality-of-life questionnaire, and self-assessment diaries were provided to
      record stool count and consistency, symptom severity, and medication consumption.
      Of the 61 patients enrolled, six did not meet the inclusion criteria and three
      were lost to follow-up. Of the remaining 52 patients with IBS-D, the average
      number of bowel movements per day was significantly reduced for patients treated
      with B. coagulans GBI-30, 6086 when compared to placebo (P = 0.042). Large
      variability in baseline scores prevented the assessment of severity scores and
      quality of life. This small pilot study provides evidence that the proprietary B.
      coagulans GBI-30, 6086 probiotic is safe and effective for reducing daily bowel
      movements in patients with IBS-D.

PMID- 20140276
TI  - Gateways to clinical trials.
AB  - [Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir
      dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren
      fumarate, AMG-221, Amlodipine besylate/olmesartan medoxomil, Aprepitant;
      Bavituximab, Bevacizumab, Bexarotene, BIBW-2992, BMS-690514, Bortezomib,
      Bosentan, Briakinumab; Capecitabine, Certolizumab pegol, Cetuximab,
      Cholecalciferol, Choline fenofibrate, Chorionic gonadotropin (human),
      Cixutumumab, Clopidogrel, CP-690550 citrate; Dabigatran, Dacetuzumab, Daclizumab,
      Dapagliflozin, Darbepoetin alfa, Dasatinib, Denosumab; Efavirenz, Elisidepsin,
      Enoxaparin, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib
      hydrochloride, Everolimus, Exenatide; Fenobam, Figitumumab, Filibuvir,
      Fondaparinux sodium, Fresolimumab; Gefitinib, Golimumab, Golnerminogene
      pradenovec; Ifosfamide, Imatinib mesylate, Ipilimumab, Ivabradine hydrochloride,
      Ixabepilone; Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride,
      Liposomal vincristine, Liraglutide; M-118, Masitinib mesylate, Metformin
      hydrochloride, Micafungin sodium, Moxifloxacin hydrochloride; Neratinib;
      Oblimersen sodium, Ofatumumab, Olmesartan medoxomil; Paclitaxel nanoparticles,
      Palifosfamide lysine, Panobacumab, Panobinostat, Patupilone, Peginterferon alfa
      2a, Pegylated arginine deiminase 20000, Piclozotan hydrochloride hydrate,
      Pixantrone maleate, Prasterone, Prasugrel, Prednisone, Progesterone,
      Prucalopride, pVGI.1 (VEGF-2); Retigabine, rhFSH, Rituximab, Rivaroxaban,
      Rosuvastatin calcium; Salinosporamide A, Selumetinib, Sipuleucel-T, Somatropin,
      Sorafenib, SSR-244738, Sunitinib malate; Tamoxifen citrate, Teduglutide,
      Telavancin hydrochloride, Telmisartan, Telmisartan/amlodipine,
      Telmisartan/hydrochlorothiazide, Temsirolimus, Tenofovir disoproxil fumarate,
      Tipifarnib, Tolvaptan, Trastuzumab, Trastuzumab-MCC-DM1, Travoprost,
      Tremelimumab; Valsartan/amlodipine besylate, Valsartan/amlodipine
      besylate/hydrochlorothiazide, Valsartan/hydrochlorothiazide, Vandetanib,
      Vorinostat.

PMID- 20140277
TI  - Kisspeptin: a novel role in the regulation of reproductive function.
AB  - Kisspeptin appears to have a pivotal role in the regulation of reproductive
      function and may have a therapeutic role in the treatment of disorders of
      reproduction. In this review we summarise the evidence regarding kisspeptin and
      its function in the hypothalamic pituitary gonadal axis and also examine future
      therapeutic applications.

PMID- 20140278
TI  - The role of Wnt signaling in neuroprotection.
AB  - The Wnt signaling pathway has a role in several cellular processes, including
      cellular communication, embryonic development and cancer. Recent studies show
      that the Wnt pathway also has an important role in some aspects of neuronal
      circuit development, such as neuronal migration, synaptic differentiation, mature
      synapse modulation and synaptic plasticity. Wnt signaling begins during neural
      development and is crucial for long-term potentiation in the adult brain. The Wnt
      pathway may have potential in the prevention of neurodegenerative diseases that
      involve synaptic impairment. Several years ago our laboratory found a
      relationship between the loss of Wnt signaling and amyloid-beta-peptide (Abeta)
      neurotoxicity, which is involved in Alzheimer's disease (AD). The activation of
      the Wnt signaling cascade prevents Abeta-dependent cytotoxic effects. We proposed
      that beta-catenin-dependent Wnt ligands have a role in the modulation of
      presynaptic processes such as neurotransmitter release. beta-catenin-independent
      Wnt signaling controls the postsynaptic site, increasing the incorporation of PSD
      95 and glutamatergic receptors in the postsynaptic region. This could prevent the
      effects of Abeta exposure at the postsynaptic level. The study of the Wnt pathway
      is a promising approach in the search for possible targets to fight the
      deleterious effects of neurodegenerative conditions such as AD.

PMID- 20140279
TI  - Targeted therapy for advanced prostate cancer: Looking through new lenses.
AB  - Prostate cancer is the most common noncutaneous malignancy in men and also the
      third leading cause of death due to cancer in males. The conventional initial
      therapy for localized advanced or metastatic disease is hormone or androgen
      deprivation therapy. Although hormone-based therapies generally result in rapid
      responses, the disease then progresses to a phase when they fail to control the
      malignancy despite castrate testosterone levels. Some patients with castration
      resistant prostate cancer continue to respond to secondary hormonal
      manipulations, and docetaxel-based chemotherapy improves median survival to about
      18 months. Prostate cancer is termed hormone-refractory when it no longer
      responds to hormonal therapy. Currently, other therapeutic options, such as
      radical prostatectomy, radiation therapy or cryotherapy offer improvement in
      survival mostly in early stages. New therapy approaches based on a deeper
      understanding of especially metastatic prostate cancer are of vital importance.
      Here we discuss up-to-date clinical trials of agents with novel targets and
      present paradigms in prostate cancer vaccine therapy, metastasis suppressor
      genes, and some provocative findings on combination therapies of cytotoxic
      agents, which might provide a platform for developing effective treatment for
      advanced prostate cancer.

PMID- 20140281
TI  - Molecule of the Month. Nalfurafine hydrochloride.

PMID- 20140280
TI  - BRCA in breast cancer: from risk assessment to therapeutic prediction.
AB  - BRCA1/2 mutations are the most commonly identified germ line gene mutations in
      patients with hereditary breast cancer. These proteins have many critical
      cellular functions, including repair of DNA double-strand breaks. The role of
      defective BRCA1/2 as a predictor of response to DNA-damaging agents has been
      studied extensively in preclinical models, but prospective clinical validation is
      lacking. Poly [ADP-ribose] polymerase (PARP) inhibitors illustrate the concept of
      synthetic lethality in cells with defective BRCA1/2 and numerous PARP inhibitors
      are being evaluated in patients with BRCA1/2-associated tumors. BRCA1/2 mutation
      or functional loss will likely serve as a useful predictive biomarker of response
      to treatment with PARP inhibitors.

PMID- 20140282
TI  - World Immune Regulation Meeting (WIRM)--III: special focus on regulatory and
      effector mechanisms.
AB  - Immune regulation is one of the most important topics in basic and clinical
      research, and IL-17-producing T helper cells (Th17) cells and regulatory T-cells
      (Tregs) are at the forefront of immunological research. The annual World Immune
      Regulation Meeting gathers some of the best experts in this field, and this
      year's meeting included presentations on new regulators of Th17 differentiation,
      novel mechanisms of immunosuppression by Tregs, and innovative systems for the ex
      vivo generation of Tregs. Novel targets for allergic inflammation were also
      discussed.

PMID- 20140283
TI  - Optimizing drugs for local delivery.
AB  - An international panel of speakers together with approximately 70 delegates were
      brought together by The Society for Medicines Research's symposium on Optimising
      Drugs for Local Delivery, held on June 11, 2009 at the Novartis Institutes for
      Biomedical Research, Horsham, UK. The focus of the conference was on the delivery
      of drugs direct to the site of action and the consequences of this delivery route
      on delivery technologies, formulation science and molecular design.

PMID- 20140284
TI  - [A "darwinian" prospective on the future of Angiology and Vascular Surgery].

PMID- 20140285
TI  - [Revista Portuguesa de Cirurgia Cardio-Toracica e Vascular. Highlights].

PMID- 20140286
TI  - [DiGeorge syndrome and vascular ring. An unusual association with
      multidisciplinary approach].
AB  - Velo-cardio-facial syndrome/DiGeorge/CATCH 22 is a spectrum of association,
      characterized by unusual face, cleft or incompetent palate, congenital heart
      disease with defects of the outflow tracts, absence of the thymus and parathyroid
      glands, often associated with developmental and behavioral disorders. This
      association is caused by a microdeletion in chromosome band 22q11.2. In a 4-month
      old infant, with obstructive lower respiratory distress and poor weight gain
      since 2 months of age, truncus arteriosus was diagnosed and surgically corrected.
      On the postoperative period maintained dependency on mechanical ventilation, with
      persistent hypoventilation of the left lung. Fiberoptic bronchoscopy revealed
      complete obstruction of the left main bronchus by an extrinsic compression due to
      a vascular ring diagnosed by cardiac catheterization that showed a common
      anomalous origin of both right and left subclavian arteries and the ligamentum
      arteriosum. A second surgery by left lateral thoracotomy corrected the vascular
      ring. The maintenance of the collapse of the left main bronchus led to selective
      endobronchial stenting. The migration of the stent to the trachea, with acute
      respiratory distress, required emergent endoscopic removal of the stent.
      Thereafter, the evolution was uneventful. The association of DiGeorge syndrome
      with vascular ring is unusual. Unexpected evolution in these patients require a
      multidisciplinary technical approach for diagnosis and eventual emergent
      intervention.

PMID- 20140287
TI  - [Primary myxoma of the pulmonary artery. Clinical report].
AB  - The cardiac myxoma is a benign clinical entity, characterised by the growth of a
      gelatinous mass composed by primary connective tissue and stroma, representing
      the most common cardiac tumour. Usually found within one of the cardiac chambers,
      it affects the left atrium in 75% of the cases. Rare cases in literature describe
      extra-cardiac locations of myxomas. In this paper, the authors report the
      clinical case of a patient with a primary myxoma of the pulmonary artery.

PMID- 20140288
TI  - [Castleman disease with pericardial location. Third case of the literature].
AB  - An intra-thoracic mass is a diagnostic challenge. We report the clinical case of
      an intra-thoracic mass which was incidentally detected in a 14-year old
      adolescent after a chest X-rays. The clinical investigation revealed a
      pericardial tumor. The immunohistological examination was consistent with
      Castleman disease. The rarity of this location was confirmed in the literature
      with only two cases previously published, to our knowledge.

PMID- 20140289
TI  - [Mediastinal teratoma with malignant transformation of the somatic component.
      Clinical report].
AB  - Mediastinal germ cell tumours (M-GCT) are rare forms of neoplasms compared with
      other tumours of the same location. They are classified in seminomas, malignant
      non-seminomatous GCT and teratomas. The malignant transformation of the somatic
      component of the teratoma, with sarcomatous or carcinomatous degeneration, is
      even more uncommon. We report the clinical case of a 32 year old man who
      presented with severe chest pain on the right hemithorax. The image exams
      revealed the existence of a large heterogeneous lesion with a diameter of 7.7 cm,
      with areas of lipomatous density and a calcic image with the appearance of a
      tooth, in the right projection of the anterior mediastinum, in the vicinity of
      the large vessels, compatible with teratoma. The transthoracic biopsy (CT guided)
      showed morphologic aspects of sarcoma. The patient was operated on with the en
      bloc resection of the mediastinal mass, right lung, a segment of the pericardium
      and the thymus. The pathological studies showed a teratoma with malignant
      transformation of the mesenquimatous component, with muscular differentiation
      into leiomiosarcoma and rabdomiosarcoma. After surgery, the patient was treated
      with a scheme of doxorubicin and ifosfamide. The most prominent concepts related
      to this clinical entity, as well as its treatment, are debated in this article,
      based on the most recent publications dedicated to the subject.

PMID- 20140290
TI  - [The utilization of the "simplified technique" in the simultaneous management of
      independent thoracic and abdominal aortic aneurysms. A clinical report].
AB  - The coexistence of independent aneurysms of the thoracic and abdominal aorta in a
      single individual, with operative indication has been regarded, since ever, as an
      enormous challenge to the vascular surgeons and is a source of controversy,
      regarding the hierarchy, priorities and methods of expeditious management. The
      authors report the clinical case of a 65 years old male, with a descending
      thoracic aortic aneurysm, extended to the abdominal visceral vessels, having 6.5
      cm of maximum size, together with an infrarenal aortic aneurysm, with 4.5 cm of
      major diameter. The patient underwent the surgical treatment of both aneurysms,
      in the same operation, utilizing the "simplified technique", introduced by
      ourselves in 1984, for the management of thoracoabdominal aortic aneurysms. The
      efficacy, safety and excellency of the procedure as well as of the clinical
      result, assessed by angio-CT scans, allow us to enhance one more indication for
      the "simplified technique" in the management of complex aortic pathology, thus
      justifying its presentation and divulgation.

PMID- 20140291
TI  - [High output heart failure due to an iatrogenic arteriovenous fistula after
      cardiac catheterization].
AB  - The occurrence of an arteriovenous fistula is a potential complication of cardiac
      catheterization. Most of these fistulas cause no harm. We report the clinical
      case of a 70 years old woman with high-output heart failure caused by an
      arteriovenous fistula (FAV) in the groin. The fistula was successfully closed by
      surgical repair and the heart failure was resolved. This case confirms the
      potential harmfulness for the vascular bed of certain surgical/endovascular
      interventions and intravascular monitoring techniques. When heart failure of
      uncertain etiology appears in patients previously submitted to one of the above
      mentioned procedures, a careful clinical examination can lead to a correct
      diagnosis of iatrogenic FAV, whose surgical correction is usually followed by the
      restoration of a normal cardiac function.

PMID- 20140292
TI  - [Chronic contained rupture of a descending thoracic aortic aneurysm simulating an
      esophagus tumor. Conventional surgical management].
AB  - The authors report the clinic case of a 54 years old male, whose chief complaints
      were dysphagia for solid foods, epigastralgias and remarkable weight loss, of 20
      kilos in two months. Admitted in another hospital with the diagnosis of esophagus
      tumor, an upper G.I. endoscopy disclosed an extensive external compresion of the
      esophagus middle third and the CT-chest scans revealed a large descending
      thoracic aortic aneurysm, in chronic contained rupture, as the cause of the
      compression. The patient was immediately transferred to our hospital and
      underwent the conventional surgical management, consisting in the aneurysm
      resection and replacement with a 30 mm Dacron prosthesis. The post-operative
      course was uneventful and reviewed four months following the operation he was
      found in good condition, asymptomatic and displaying a remarkable weight gain. In
      era of a progressive expansion of the field of the endovascular management of
      thoracic aortic aneurysms, some cases, like the present clinical case, seem to
      represent a formal contraindication to the endovascular technology, due to the
      irreducible external compression of organs such as the esophagus, thus remaining
      an exclusive indication for the conventional surgical management.

PMID- 20140293
TI  - [The impact of selective clamping of portal vein in hepatocellular function. An
      experimental study].
AB  - The influence of selective clamping of the elements of hepatic pedicle in the
      hepatocellular function and viability were evaluated in our department. AIM:
      Study the effect of selective clamping of the portal vein (CPV) in hepatocellular
      function in an animal model with normal liver. METHOD: Three groups of Wistar
      rats (males, 2 months) were subjected a CPV for 60 min: group A (n=21) submitted
      to a continuous inflow occlusion; group B (n=12) underwent to a CPV for 30 min
      with 5 min of reperfusion; group C (n=10) underwent a CPV for 15 min with 5 min
      of reperfusion. The group D (n=9) was not subjected to a CPV. A hepatic biopsy
      was done at the end of surgery. The degree of tissue injury was evaluated using:
      1) blood markers: AST, ALT, total bilirubin (TB), GGT alkaline-phosphatase, LDH
      and hepatic extraction fraction (HEF) by radioisotopic methods three days before
      laparotomy (BS) and after surgery (AS); 2) apoptosis, necrosis were investigated
      after collagenase cell isolation from hepatectomy pieces by flow-cytometry using
      the followed probes: propidium-iodide and annexin-V. STATISTICAL ANALYSIS:
      variance analysis, post-hoc comparisons by Turkey-test (p<0.05). RESULTS: 1)
      Mortality: Group A - 62%, Group B - 17%, Group C - 30%, Group D - 0% (p<0.03). 2)
      We observed statistical differences in these parameters: ALT (p<0,025) and LDH
      (p<0,002) preferentially in groups A but without differences between the A,B,C
      and D Groups (ns). 3) We also verified a significant decrease in HEF values
      (p<0,0001) preferentially in group A without differences between the groups. 4)
      No difference were observed when analysed apoptosis and necrosis and cell
      viability between the groups. CONCLUSIONS: Postoperative liver failure is the
      leading cause of mortality after hepatectomy, however selective clamping of the
      portal vein, is reflected in an increase in cell viability and a decrease in the
      type of cell death (necrosis ou apoptosis) compared to studies carried out
      previously by us and thus may be regarded as an alternative to the Pringle
      maneuver. However, selective clamping of the portal vein for periods above 30'
      should be avoided, given the high mortality verified.

PMID- 20140295
TI  - Some ultrastructural observations of the vegetative, resting and excysting
      ciliate, urostyla grandis (urostylidae, hypotrichida).
AB  - In order to reveal the differentiation characteristics of organelles of ciliates
      under different physiological status, the cellular ultrastructure of Urostyla
      grandis was studied by transmission electron microscopy. In the resting cells
      most ciliary shafts, kinetosomes and sub-pellicle microtubules were resorbed, and
      the endoplasmic reticulum (ER) disappeared with the autophagocytosis taking place
      within the cytoplasm. As well, the nuclear matrix of the macronucleus was
      extruded into the cytoplasm, forming pseudopodia-like structures with large
      quantities of heterochromatin (CH) attached to the inner nuclear membrane. During
      excystment, membraneous structures developed and gradually increased in number to
      form the ER. Autophagic vacuoles (AVs) appeared containing mitochondria,
      paraglycogen particles (PGP), membranous structures, etc. Moreover, the number of
      nucleoli decreased with the chromatin, condensing in parallel with the process of
      recombination. Based on these observations, it could be concluded that the de
      differentiation of microtubular organelles and the changes occurring in
      macronuclei in the resting Urostyla grandis, as well as the differentiation of
      cytoplasmic organelles, digestion by AVs, and the recombination of chromatin
      during excystment, are not similar to events that occur in non-kinetosome
      resorbing cysts (NKR).

PMID- 20140294
TI  - [Displastic aneurysm of the internal carotid artery simulating a carotid body
      tumor].

PMID- 20140296
TI  - Bioactivity of crude ethanol extract and fractions of Eugenia uniflora
      (Myrtaceae) in the hepatopancreas of Oreochromis niloticus L.
AB  - This study evaluates the bioactivity of the crude ethanol extract and ethyl
      acetate, hexane and chloroform fractions obtained from Eugenia uniflora leaves
      using the hepatopancreas of Oreochromis niloticus L. as an experimental model.
      The ethanol extract and fractions were administered to the fish orally with their
      feed. Twenty-four hours later, the fish were sacrificed and their livers
      dissected, fixed in neutral formalin, embedded in paraffin and sectioned.
      Histological analyses were performed using Masson's trichrome and Haematoxylin
      Eosin. Histochemical studies were performed using Feulgen, PAS (Periodic Acid
      Schiff) and PAS + salivary amylase and Sudan IV stain. The qualitative analysis
      of the material showed that the crude extract and the ethyl, chloroform and
      hexane fractions induced vasodilation, vascular congestion and toxicity due to
      the presence of eosinophilic granular cells, rodlet cells, some leukocytic
      infiltrate and rare focal necroses. The Nile tilapia proved to be a satisfactory
      model for screening plant products.

PMID- 20140297
TI  - Effect of the monocyte locomotion inhibitory factor (MLIF) produced by E.
      histolityca on cytokines and chemokine receptors in T CD4+ lymphocytes.
AB  - Entamoeba histolytica produces Monocyte Locomotion Inhibitory Factor (MLIF),
      which may contribute to the delayed inflammation observed in amoebic hepatic
      abscesses. Leukocytes are affected through the modulation of cytokine expression
      and/or production. We evaluated the effects of MLIF on the activation and
      production of intracellular cytokines in human CD4+ T lymphocytes by flow
      cytometry. Cells were stimulated for 24 h with PMA, MLIF, or PMA+MLIF. Cellular
      activation was measured using anti-CD69. Th1/Th2 production was studied by the
      expression of intracellular cytokines and cytokine/chemokine receptors. MLIF
      increased CD69 and induced the over-expression of the IL-lss, IFN-gamma, IL-2, IL
      4, and IL-10 intracellular cytokines; PMA+MLIF inhibited Th1 cytokine (IFN-gamma)
      and increased Th2 cytokines (IL-4 and IL-10). The co-expression of the cytokine
      and chemokine receptors IFN-gamma/CCR5 and IL-1ss/CCR5 was inhibited by PMA+MLIF
      and Th2 co-expression was increased. MLIF effects varied depending on the
      conditions. MLIF alone activated the Th1 and Th2 cytokines and cytokine/receptor
      expression; however, PMA+MLIF increased the expression of Th2 but inhibited it in
      Th1.

PMID- 20140298
TI  - Biofilm formation and acyl homoserine lactone production in Hafnia alvei isolated
      from raw milk.
AB  - The objective of this study was to detect the presence of acyl homoserine
      lactones (AHLs), signal molecules of the quorum sensing system in biofilm formed
      by Hafnia alvei strains. It also evaluated the effect of synthetic quorum sensing
      inhibitors in biofilm formation. AHLs were assayed using well diffusion
      techniques, thin layer chromatography (TLC) and detection directly in biofilm
      with biomonitors. The extracts obtained from planktonic and sessile cell of H.
      alvei induced at least two of three monitor strains evaluated. The presence of
      AHLs with up to six carbon atoms was confirmed by TLC. Biofilm formation by H.
      alvei was inhibited by furanone, as demonstrated by 96-well assay of crystal
      violet in microtitre plates and by scanning electron microscopy. The H. alvei 071
      hall mutant was deficient in biofilm formation. All these results showed that the
      quorum sensing system is probably involved in the regulation of biofilm formation
      by H. alvei.

PMID- 20140299
TI  - Mycophenolate mofetil versus Rapamycin in Han: SPRD rats with Polycystic Kidney
      Disease.
AB  - OBJECTIVE: We aimed to explore the effect of Mycophenolate mofetil (MMF) on loss
      of renal function and cyst progression compared to rapamycin in Han: SPRD rats.
      We also sought to assess whether the effect of combination therapy of MMF plus
      rapamycin was better than that of monotherapy. METHODS: Sixty heterozygous (Cy/+)
      and littermate control (+/+) male Han: SPRD rats were weaned at 4 weeks of age,
      then divided into four groups randomly to receive different treatments by
      intragastric administration for 2 months: vehicle-treated group as control, MMF
      treated group (20mg/kg/day), rapamycin-treated group (2mg/kg/day), and MMF+Rapa-
      treated group (MMF 20mg/kg/day plus Rapamycin 2mg/kg/day). RESULLS: After 2
      months of treatment, rapamycin caused a 22 % decrease in body weight in
      comparison to the control group, whereas MMF had no significant effect on weight
      gain. The steady increase of BUN in Cy/+ rats was reduced by 15% in MMF-treated
      Cy/+ rats. However, rapamycin and combination therapy reduced BUN by 42% and 43%,
      respectively. CCr was 0.93+/-0.11ml/min in vehicle-treated Cy/+ rats, 1.67+/-0.23
      ml/min in MMF-treated Cy/+ rats (P<0.05), 1.72+/-0.44 ml/min and 1.83+/-0.21
      ml/min in rapamycin- and MMF+Rapa-treated Cy/+ rats, respectively (.P<0.01). Cyst
      volume density was 57.1 % in vehicle-treated Cy/+ rats, 45.2% in MMF-treated Cy/+
      rats (P<0.05), 32.9% and 37.7% in rapamycin- and MMF+Rapa-treated Cy/+ rats,
      respectively (P<0.01). MMF markedly ameliorated interstitial inflammation and
      fibrosis. Rapamycin showed a similar effect on interstitial inflammation and
      fibrosis, but to a lesser degree. CONCLUSION: MMF is more tolerable than
      rapamycin and can retard deterioration of renal function in Han: SPRD rats,
      though its effect is weaker than that of rapamycin. Combination therapy does not
      exert more favorable effect than monotherapy.

PMID- 20140300
TI  - Alterations in core histone variant ratios during maize root differentiation,
      callus formation and in response to plant hormone treatment.
AB  - Although several histone variants have been studied in both animal and plant
      organisms, little is known about their distribution during processes that involve
      alterations in chromatin function, such as differentiation, dedifferentiation and
      hormone treatment. In this study we evaluated the ratio of each histone variant
      in each of the four core histone classes in the three developmental zones of
      maize (Zea mays L.) root and in callus cultures derived from them, in order to
      define possible alterations either during plant cell differentiation or
      dedifferentiation. We also evaluated core histone variant ratios in the
      developmental zones of roots treated with auxin and gibberellin in order to
      examine the effects of exogenously applied plant hormones to histone variant
      distribution. Finally, immunohistochemical detection was used to identify the
      root tissues containing modified forms of core histones and correlates them with
      the physiological status of the plant cells. According to the results presented
      in this study, histone variant ratios are altered in all the cases examined, i.e.
      in the developmental zones of maize root, in callus cultures derived from them
      and in the developmental zones of roots treated either with auxin or gibberellin.
      We propose that the alterations in linker histone variant ratios are correlated
      with plant cell differentiation and physiological status in each case.

PMID- 20140301
TI  - VEGFA polymorphisms and cardiovascular anomalies in 22q11 microdeletion syndrome:
      a case-control and family-based study.
AB  - Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes.
      Most patients share a common 3Mb deletion, but the clinical manifestations are
      very heterogeneous. Congenital heart disease is present in 50-80% of patients and
      is a significant cause of morbidity and mortality. The phenotypic variability
      suggests the presence of modifiers. Polymorphisms in the VEGFA gene, coding for
      the vascular endothelial growth factor A, have been associated with non-syndromic
      congenital heart disease, as well as with the presence of cardiovascular
      anomalies in patients with microdeletion 22q11. We evaluated the association of
      VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G
      (rs2010963) with congenital heart disease in Chilean patients with microdeletion
      22q11. The study was performed using case-control and family-based association
      designs. We evaluated 122 patients with microdeletion 22q11 and known anatomy of
      the heart and great vessels, and their parents. Half the patients had congenital
      heart disease. We obtained no evidence of association by either method of
      analysis. Our results provide further evidence of the incomplete penetrance of
      the cardiovascular phenotype of microdeletion 22ql 1, but do not support
      association between VEGFA promoter polymorphisms and the presence of congenital
      heart disease in Chilean patients with this syndrome.

PMID- 20140302
TI  - Donepezil reverses buprenorphine-induced central respiratory depression in
      anesthetized rabbits.
AB  - Buprenorphine is a mixed opioid receptor agonist-antagonist used in acute and
      chronic pain management. Although this agent's analgesic effect increases in a
      dose-dependent manner, buprenorphine-induced respiratory depression shows a
      marked ceiling effect at higher doses, which is considered to be an indicator of
      safety. Nevertheless, cases of overdose mortality or severe respiratory
      depression associated with buprenorphine use have been reported. Naloxone can
      reverse buprenorphine-induced respiratory depression, but is slow-acting and
      unstable, meaning that new drug candidates able to specifically antagonize
      buprenorphine-induced respiratory depression are needed in order to enable
      maximal analgesic effect without respiratory depression. Acetylcholine is an
      excitatory neurotransmitter in central respiratory control. We previously showed
      that a long-acting acetylcholinesterase inhibitor, donepezil, antagonizes
      morphine-induced respiratory depression. We have now investigated how donepezil
      affects buprenorphine-induced respiratory depression in anesthetized, paralyzed,
      and artificially ventilated rabbits. We measured phrenic nerve discharge as an
      Index of respiratory rate and amplitude, and compared discharges following the
      injection of buprenorphine with discharges following the injection of donepezil.
      Buprenorphine-induced suppression of the respiratory rate and respiratory
      amplitude was antagonized by donepezil (78.4 +/- 4.8 %, 92.3% +/- 22.8 % of
      control, respectively). These findings indicate that systemically administered
      donepezil restores buprenorphine-induced respiratory depression in anesthetized
      rabbits.

PMID- 20140303
TI  - DNA damage and related modifier genes in Italian cystic fibrosis patients.
AB  - Cystic Fibrosis (CF) is an autosomal recessive multisystemic disorder showing a
      highly heterogeneous phenotype, even among siblings carrying identical CFTR
      mutations. Moreover, oxidative stress is of central importance in the
      pathogenesis of cystic fibrosis. The present study seeks to value the presence of
      oxidative damage in CF patients and the possible modifier effect of repair and
      glutathione-S-transferase genes. We analysed the presence of DNA damage in
      leukocytes of 63 CF patients at an Italian CF centre and 63 controls, through the
      alkaline Comet assay to detect DNA strand breaks. Furthermore, controls and 93 CF
      subjects were genotyped for 5 genes by RFLP-PCR (XRCC1,0GG1,GSTP1) and PCR assay
      (GSTM1, GSTT1). No difference in Comet assay values was observed comparing
      controls to CF patients, although CF subjects showed slightly higher mean values.
      The crude Odds-Ratio (OR) was higher than one for XRCC1 and GSTP1 genotypes and
      liver status and for XRCC1 and OGG1 genotypes and pancreatic insufficiency, but
      in all cases the p-values were not significant. In this case-control study,
      neither DNA damage nor gene polymorphisms seem to influence CF manifestation.

PMID- 20140304
TI  - Upregulation of liver inducible nitric oxide synthase following thyroid hormone
      preconditioning: suppression by N-acetylcysteine.
AB  - 3,3-5-L-Triiodothyronine (T(3)) exerts significant protection against ischemia
      reperfusion (IR) liver injury in rats. Considering that the underlying mechanisms
      are unknown, the aim of this study was to assess the involvement of inducible
      nitric oxide synthase (iNOS) expression and oxidative stress in T(3)
      preconditioning (PC). Male Sprague-Dawley rats given a single dose of 0.1 mg of
      T(3)/kg were subjected to 1-hour ischemia followed by 20 hours reperfusion, in
      groups of animals pretreated with 0.5 g of N-acetylcysteine (NAC)/kg 0.5-hour
      prior to T3 or with the respective control vehicles. At the end of the
      reperfusion period, liver samples were taken for analysis of iNOS mRNA levels (RT
      PCR), liver NOS activity, and hepatic histology. T(3) protected against hepatic
      IR injury, with 119% enhancement in liver iNOS mRNA/18S rRNA ratios (p<0.05) and
      12.7-fold increase (p<0.05) in NOS activity in T(3)-treated animals subjected to
      IR over values in control-sham operated rats, with a net 7.7-fold enhancement
      (p<0.05) in the net effect of T(3) on liver iNOS expression and a net enhancement
      of 0.58 units in NOS activity, changes that were abolished by NAC treatment
      before T(3). It is concluded that T(3)-induced liver PC is associated with
      upregulation of iNOS expression as a protective mechanisms against IR injury,
      which is achieved through development of transient and reversible oxidative
      stress.

PMID- 20140305
TI  - Y chromosomal STR polymorphism in northern Chinese populations.
AB  - Y chromosomal STRs show sufficient variability among individduals in a population
      and a high degree of geographical differentiation, such that their polymorphic
      character makes them especially suited for population genetic studies. To
      investigate the polymorphism of a set of 17 Y-STR loci in northern China, we
      genotyped the 17 Y chromosomal STR loci in a population sample of 377 unrelated
      males from eight ethnic populations in northern China. We calculated the
      haplotype frequencies, Rst value and carried out the analysis of molecular
      variance (AMOVA). We then drew the multidimensional scaling analysis (MDS) plot
      and phylogenetic tree based on the Rst value. All populations showed a high level
      of haplotype diversity, with low inter-population variance as measured by an
      analysis of molecular variance. However, the genetic distances were significant
      when the eight populations were compared to other populations. By MDS and the
      phylogenetic tree, we found that the eight populations had a close relationship
      and Xibo had a northeast origination.

PMID- 20140306
TI  - Characterization of calreticulin expression in mouse endometrium during embryo
      implantation.
AB  - Calreticulin (CRT), a Ca(2+)-binding storage protein and chaperone in the
      endoplasmic reticulum, modulates cell adhesiveness and integrin-dependent Ca(2+)
      signaling. However, the role of CRT during implantation remains poorly
      understood. In the present study, we characterized the expression of CRT mRNA and
      the protein in mouse endometria from pregnancy DI to D7. Real-Time PCR and in
      situ hybridization results showed that the levels of CRT mRNA in the endometria
      of pregnant mice were significantly higher than those of non-pregnant mice
      (P<0.05), and increased gradually from pregnancy DI to D4, reaching the maximum
      level on D4, followed by a plateau from D4 to D7. Using immunofluorescence
      histochemistry and western blot, changes of CRT expression in the endometria of
      pregnant mice were consistent with the expression of CRT mRNA. Furthermore,
      antisense CRT oligodeoxynucleotide was injected into the uterus horns of pregnant
      mice (D3) to investigate its effect on embryo implantation. The result showed
      that the number of implanted embryos markedly decreased in the side of uterine
      horns receiving antisense CRT oligodeoxynucleotide(i(>)<0.05). These findings
      suggest that CRT may play an important role in embryo implantation in mice.

PMID- 20140307
TI  - Induction of programmed cell death by Prangos uloptera, a medicinal plant.
AB  - Inhibition of the cell growth or induction of cell death is the most promising
      area in cancer therapy. The induction of apoptosis by dichloromethane extract of
      Prangos uloptera was evaluated on the McCoy cell line. This plant's roots, aerial
      parts and fruit have medicinal value. Cell growth inhibitory and cell
      cytotoxicity effects of the extract were assayed by MTT and Trypan-blue tests,
      respectively. Morphological changes and DNA fragmentation were also evaluated.
      The viability tests showed 0.49 and 0.3 mg/ml as 50% inhibition concentration and
      50% cytotoxicity concentration after 24 hours of treatment, respectively.
      Fluorescent microscopy analysis revealed chromatin fragmentation and scanning
      electron microscopy showed cell shrinkage and cytoplasmic blebbing. These
      findings were confirmed by DNA fragmentation analysis. The results demonstrated
      efficient induction of apoptosis by the plant extract in moderate concentrations,
      but administration of higher concentrations showed that the primary manner of
      cell death was necrosis.

PMID- 20140308
TI  - [Human papillomavirus (HPV) genotypes in cervix uterine cancer patients in a
      public hospital and private clinic from Santiago, Chile].
AB  - We compared HPV genotypes among squamous cervical cancer samples from a public
      hospital (n = 55) and a private clinic (n = 35 cases) of Santiago. Paraffin
      embedded specimens were analyzed by PCR followed by an immunoenzimatic assay.
      Reverse line blotting was used for the identification of 36 HPV genotypes. We
      found HPVDNAm 94.4% of all cancers. Single mfections: HPV16: 40.0%, (clinic
      37.1%, hospital 41.8%) VPH18:7.8% (clinic 2.9%, hospital 10.9%); single+multiple
      mfections: VPH16: 61.1% (clinic 53.1%, hospital 71.7%), VPH18: 34.4% (clinic
      21.9%, hospital 45.2%). HPV16 orHPV18 occurredin 75.6% of cases, higher in the
      hospital than the clinic (87.3%-95% CI: 84.9-96.3 - and 57. l%-95% CI: 46.6-66 -
      respectively, p = 0.002). Other genotypes in single mfections: HPV 26, 31, 33,
      45, 58, 67; in co-mfections: HPV 35,52,56,59 and 66. HPV16 but specially HPV 18
      were significantly more frequent in the public hospital; 75.6% of squamous
      cervical cancer were associated to the vaccine preventable HPV16/18.

PMID- 20140309
TI  - [PIRO classification in pediatric severe sepsis and septic shock: a new model for
      staging and its potential usefulness in prognoses].
AB  - BACKGROUND: Sepsis is a dynamic process that involves complex interactions
      between the pathogenic micro-organisms and the host. The understanding of this
      heterogeneous disease has led to the development of a new system for
      stratification of septic patients: the PIRO system: Predisposition (P) 
      Insult/Infection (I) -Response (R) -Organ disfunction (O), a classification aimed
      to determine the risk of death in patients with sepsis. Only a few studies have
      validated this classification system in children. OBJECTIVE: To empirically test
      the accuracy of the PIRO system in pediatric patients with septic shock and
      severe sepsis and associate its individual components to predict mortality.
      PATIENTS AND METHOD: A retrospective chart review was performed in a 13 bed PICU
      during 24 months (January 2006 to December 2007) Demographic, clinical and
      microbiological data were recorded in all patients with a diagnosis of septic
      shock and severe sepsis during the study period. For all patients the PIRO
      classification system was applied by one of four authors using paramethers
      measured at admission. RESULTS: Atotal of 42 patients were included with a mean
      age of 11 months (range 3.25-58.3) of which 52% were male. Overall mortality was
      19% and variables associated with mortality for each category were: (P) Chronic
      illness (OR: 7 IC95% 0.95-51) and Immunodeficiency (OR: 6.2; IC95% 1.1-35.2); (R)
      leucopema (OR 9; IC95%: 1.96-41.72); (O) more thanthree dysfunctional organs (OR:
      6.1; IC95%: 1.22-31). None of the (I) variables were associated with mortality.
      CONCLUSIONS: The PIRO classification system identified factors associated with a
      fatal outcome in our population. The test is relatively simple to apply but cross
      sectional studies are required to define variables associated with death that
      should then be prospectivelly validated.

PMID- 20140310
TI  - [Leonard bernstein and "casamiento de negros"].

PMID- 20140311
TI  - [Amphotericin B deoxycholate prescription and adverse events in a Chilean
      university hospital].
AB  - Amphotericin B deoxycholate is associated with infusion-related toxicity and
      renal toxicity. PURPOSE: To evaluate medical indications of this compound in a
      tertiary care center, analyze adverse reactions, infusion protocols and outcome
      of treated patients. PATIENTS AND METHODS: Retrospective analysis of 39
      treatments indicated in 33 patients during 2007, exploring indications, infusion
      protocols and renal protective measures, infusion-related adverse reactions,
      nephrotoxicity, hypokalemia and outcomes. RESULTS: On average, therapy lasted 12
      days (2 to 39) and reached 600 mg of accumulated dose (100 to 1950) respectively.
      24-hours infusions were applied in 63.2% of prescriptions and 35.9% received a 4
      6 hour infusion schedule. In addition, 36.8% received daily a saline infusion
      before amphotericin. Adverse reactions were observed in 40% of treatments,
      predominating fever (25%). Nonetheless, nephrotoxicity was infrequent (9.4%), of
      low magnitude, only affecting patients without previous renal disease, and not
      requiring dialysis. Hypokalemia developed in 21.6% of treatments. More than half
      of medical indications were empirical (59%), for presumed infections by either
      filamentous fungi or yeasts. In the subgroup with microbiological information,
      main indications were invasive aspergillosis (15.4% of total), systemic
      candidiasis (12.8%) or meningeal cryptococcosis (10.3%). A favorable response was
      registered in 41%, and only 48.5% of patients survived. In a multivariate
      analysis, only age > 60 years remained as an independent factor for developing
      infusion-related adverse reactions. In the same manner, a SOFA score > 3 and
      corticosteroids administration at the same time than amphotericin B, were
      independently associated to a fatal outcome. CONCLUSION: infusion-related adverse
      reactions are frequent during amphotericin B deoxycholate therapy, but renal
      toxicity is occasionally observed. Amphotercin B was used mainly as empirical
      therapy in this study.

PMID- 20140312
TI  - [Biological risk accidents among undergraduate healthcare students: five years
      experience].
AB  - Undergraduate healthcare students are exposed to bloodborne pathogens, and data
      from developing countries is scarce. We report the experience of a comprehensive
      program dedicated to the management of this risk. The program includes financial
      coverage, a 24-hour attention system, HIV, HBV, HCV testing, and free provision
      of post-exposure antiretroviral drugs. During 2003-2007, incidence rates of these
      exposures reached 0.9 per 100 student-years. Events were only observed among
      medicine, nursing, and midwifery students, with rates highest among nursing
      students (RR 3.5 IC95 1.93 - 6.51). Cuts and needle stick injuries predominated
      (74.7% of accidents). Three students were exposed to HIV patients (1.9%), all of
      them received prophylactic drugs, infection was discarded after follow up, and
      also discarded after exposures to HBV or HCV (0.6% of all accidents). Cost per
      1000 student-year was less than 2000 USD. Healthcare students are exposed to
      biological risks during their studies and a comprehensive program is feasible in
      a developing country.

PMID- 20140313
TI  - [Report of four clinical cases of Hafnia alvei bacteremia in a pediatric cardiac
      surgery unit].
AB  - INTRODUCTION: The gram-negative bacillus Hafnia alvei is the only species of the
      genus Hafnia, family Enterobacteriaceae. It occasionally behaves as an
      opportunistic pathogen in humans, causing intestinal and respiratory infection
      and sepsis. It rarely causes bacteremia, usually of unknown focus. OBJECTIVE: To
      describe a nosocomial outbreak of four pediatric patients with bacteremia by
      Hafnia alvei. METHODS: Descriptive study using clinical records of pediatric
      patients diagnosed with Hafnia alvei bacteremia in a pediatric cardio surgical
      unit, in October 2008. RESULTS: The attack rate was 4/8 (50%), lethality rate 2/4
      (50%) and mortality 2/8 (25%). The microbiological study and pulsed-field gel
      electrophoresis confirmed the same clonal bacterial strain. DISCUSSION: The
      source of bacteremia was identified only in two patients and was associated with
      central venous catheters. The other two cases had no known infectious source.
      Epidemiological surveillance of emerging agents must be maintained.

PMID- 20140314
TI  - [Streptococcus pseudopneumoniae].

PMID- 20140315
TI  - [Varicella outbreak in a village in Uruguay].
AB  - A varicella outbreak occurred in a Uruguayan village that introduced the
      varicella vaccine in 1999 with currently high vaccination rates. AIM: To
      investigate the cause of the outbreak, vaccine effectiveness, and to describe the
      measures adopted. MATERIAL AND METHODS: Cases that occurred in the kindergarten
      and schools in the village were investigated. Vaccination cards were examined,
      history of chickenpox and clinical characteristic of the current episode were
      obtained and the outcome of the measures was evaluated. An estimate was made of
      the vaccine's effectiveness. RESULTS: 37 cases of varicella were reported, 14
      occurring in previously vaccinated children, in a one total population of 313
      children. The global effectiveness of the vaccine was 80%, and 100% for severe
      cases. A shift of cases towards older ages was demonstrated; vaccinated children
      had a trend of less fever and lower number of lesions. Immunization of healthy
      unvaccinated children, mainly adolescents stopped the outbreak. COMMENTS: The
      vaccine proved to be highly effectiveness. In an outbreak situation, immunization
      policies should consider "catch up" vaccination in non-immunized adolescents
      without a previous history of varicella.

PMID- 20140316
TI  - [Hantavirosis: clinical and epidemiological characteristics of pediatric patients
      in Chile].
AB  - BACKGROUND: The first cases of Hantavirus cardiopulmonary syndrome in children
      were described in the United States and represented 8% of the total reported
      cases; in Chile, the proportion of pediatric cases represents 15% of all national
      cases. AIM: To describe the epidemiology and clinical course of 82 children
      reported to the Chilean Ministry of Health up to 2007 and to characterize more
      extensively a subgroup of 24 children whose detailed clinical data were
      available. RESULTS: Forty patients were under 10 years old. Seventeen (17/82) of
      82 cases (20.7%) presented in the context of a family cluster. Ninety eight
      percent of cases (80/82) occurred among individuals living in rural areas and 66%
      during summer months). The overall fatality rate was 36.6%. Fever (93%),
      respiratory distress (75%) and gastrointestinal symptoms (75%) were the most
      frequent symptoms encountered in the 28 children studied more extensively.
      Abnormal blood coagulation test were significantly associated with death while an
      increased hematocrit was associated with severe cases (hemodynamic unstability).
      CONCLUSION: An early diagnosis should favor early onset of aggressive treatment
      that could potentially save lives. Increasing knowledge on the clinical
      presentation of the disease in children should improve early clinical diagnosis
      among health care professionals.

PMID- 20140317
TI  - [Microbiologic diagnosis of sexually transmitted diseases: Part II. STD of viral
      origin].
AB  - Sexually transmitted diseases are highly prevalent and a public health concern
      worldwide. Herpes simplex virus (HSV) and human papilloma virus (HPV) are
      described. The development of rapid, sensible and specific diagnostic assays has
      been difficult because of their pathogenic features. In the last years, molecular
      biology based techniques allowed a better and wider range of diagnosis, as in the
      HPV-cancer association. In this article, standardized diagnostic methodologies
      for HSV and HPV are reviewed.

PMID- 20140318
TI  - [Depression in HIV infection: prevalence, risk factors and management].
AB  - Depression is one of the main psychiatric co-morbidities in HIV infection,
      presenting with a significantly higher prevalence than in the general population
      (around 35%). Its presence has been associated with poor quality of life, HIV
      disease progression and poor adherence to antiretroviral therapy. Although
      antidepressive treatment has demonstrated effectiveness on the management of
      depressive symptoms, improvement of clinical and laboratory parameters, and
      enhancement of antiretroviral adherence, depression is frequently under diagnosed
      and under treated in these patients. We analyzed the main international findings
      on depression prevalence, risk factors, con-sequences and management in people
      with HIV disease.

PMID- 20140319
TI  - [Sooner or later].

PMID- 20140320
TI  - [Disentery and hepatic abscess in the colonial and republican Chile. Doctor
      Miguel Claro Vasquez].
AB  - The frequency and severity of dysentery and hepatic abscess during the colonial
      and republican era in Chile are reviewed. The amebian etiology was confirmed in
      both clinical entities. Also, Miguel Claro Vasquez, physician and later priest
      and bishop of the Catholic Church, was distinguished for his contribution to
      hepatic abscess surgery.

PMID- 20140321
TI  - [Brucella abortus endocarditis: survival of a 74 year old patient].
AB  - Brucellosis is not frequent in Chile but it may present with life threatening
      complications like endocarditis. The case reported refers to a 74 year old man
      admitted to the Infectious Diseases Hospital Dr. Lucio Cordova in Santiago. He
      had been febrile for 3 months with no specific symptoms. The trans-esophageal
      echocardiography confirmed multiple large vegetations and important involvement
      of the aortic valve. Blood cultures yielded Brucella abortus. The patient
      required cardiac surgery, along with antibiotics, and he had a satisfactory
      outcome, being alive at the moment of this report???. Brucellosis can be the
      responsible for prolonged fever of unknown origin. It is necessary to take in
      mind brucellosis to obtain the specific laboratory tests. For a best prognosis an
      early treatment with associated antibiotics for at least 4 a 6 weeks is
      important. If endocarditis is present valve replacement is often necessary.

PMID- 20140322
TI  - [Candida rugosa fungemia: new emergent infection case].

PMID- 20140324
TI  - Socioeconomic inequities in the health and nutrition of children in low/middle
      income countries.
AB  - OBJECTIVE: To describe the effects of social inequities on the health and
      nutrition of children in low and middle income countries. METHODS: We reviewed
      existing data on socioeconomic disparities within-countries relative to the use
      of services, nutritional status, morbidity, and mortality. A conceptual framework
      including five major hierarchical categories affecting inequities was adopted:
      socioeconomic context and position, differential exposure, differential
      vulnerability, differential health outcomes, and differential consequences. The
      search of the PubMed database since 1990 identified 244 articles related to the
      theme. Results were also analyzed from almost 100 recent national surveys,
      including Demographic Health Surveys and the UNICEF Multiple Indicator Cluster
      Surveys. RESULTS: Children from poor families are more likely, relative to those
      from better-off families, to be exposed to pathogenic agents; once they are
      exposed, they are more likely to become ill because of their lower resistance and
      lower coverage with preventive interventions. Once they become ill, they are less
      likely to have access to health services and the quality of these services is
      likely to be lower, with less access to life-saving treatments. As a consequence,
      children from poor family have higher mortality rates and are more likely to be
      undernourished. CONCLUSIONS: Except for child obesity and inadequate
      breastfeeding practices, all the other adverse conditions analyzed were more
      prevalent in children from less well-off families. Careful documentation of the
      multiple levels of determination of socioeconomic inequities in child health is
      essential for understanding the nature of this problem and for establishing
      interventions that can reduce these differences.

PMID- 20140325
TI  - Causes of the accelerated decline in child undernutrition in Northeastern Brazil
      (1986-1996-2006).
AB  - OBJECTIVE: To describe changes in prevalence of child undernutrition in
      Northeastern Brazil in two successive time periods, identifying, in each period,
      the major factors responsible for these changes. METHODS: Data analyzed are from
      probabilistic samples of underfives from three Demographic Health Surveys carried
      out in 1986 (n=1,302), 1996 (n=1,108), and 2006 (n=950). Identification of
      factors responsible for temporal changes in child undernutrition (height-for-age
      below < -2 z) took into account time changes in five potential determinants of
      child nutritional status, statistical modeling of the independent association
      between determinants and risk of undernutrition, and calculation of attributable
      fractions. RESULTS: Prevalence of child undernutrition fell by one-third between
      1986 and 1996 (from 33.9% to 22.2%) and by almost three-quarters between 1996 and
      2006 (from 22.2% to 5.9%). Improvements in maternal schooling and in the coverage
      of water and sewage services were particularly important for the decline in child
      undernutrition in the first period, while increasing purchasing power of the
      poorest families and, again, maternal schooling were more relevant in the second
      period. CONCLUSIONS: The acceleration of the decline in child undernutrition
      between the two periods was consistent with accelerated improvement of maternal
      schooling, water supply and sewage, health care, and maternal reproductive
      antecedents, as well as with the outstanding increase in purchasing power among
      the poor during the second period. If the rate of decline in growth deficits is
      kept at around the rate of the most recent period, child undernutrition will be
      controlled in the Brazilian Northeast in less than ten years. Achieving this will
      depend on sustaining the increase in purchasing power among the poor and on
      ensuring public investment in completing the universalization of access to
      essential services such as education, health, and sanitation.

PMID- 20140326
TI  - Experiences of discrimination among university students in the city of Rio de
      Janeiro.
AB  - OBJECTIVE: To understand experiences of discrimination lived by undergraduate
      students and to analyze their applicability to the construction of a Brazilian
      discrimination scale. METHODOLOGICAL PROCEDURES: In a qualitative study five
      focus groups were conducted with 43 university students from the city of Rio de
      Janeiro, Southeastern Brazil, in 2008. Students from undergraduate courses with
      different candidate/place ratios; of both sexes; self-identified as white, mixed
      or black; and belonging to two public higher education institutions were
      selected. An interview guide focusing on issues related to 'prejudice' and
      'discrimination' and asking participants about their experiences of
      discrimination was used. The method of interpretation of meanings was adopted,
      seeking to understand the context, reasons and logics of participants' speech.
      ANALYSIS OF RESULTS: Prejudice was interpreted as something belonging to the
      field of ideas, probably equivocated, and which could be either positive or
      negative. Discrimination was attributed to the field of observable behaviors and
      with an invariably negative connotation. The interpretation of a discriminatory
      event as such was influenced by subjective factors, such as personal interests
      and the level of affectivity established between individuals. However, the limit
      between what was interpreted as discriminatory or not depended strongly on the
      specific context in which the interaction among individuals occurred. Different
      situations and, at times, more than one motivation were simultaneously indicated
      as regards discriminatory experiences. Participants saw themselves as both
      victims and perpetrators of discrimination. CONCLUSIONS: The interpretation of an
      event as discriminatory involves great complexity and the experiences of
      discrimination can hardly be generalized. When evident, the reasons for which
      individuals suppose they have been discriminated against may be multiple and
      associated with each other. Such aspects must be considered when constructing
      items for the discrimination scale.

PMID- 20140327
TI  - Locus of control and contraceptive knowledge, attitude and practice among
      university students.
AB  - OBJECTIVE: To assess the relationship between locus of control and knowledge,
      attitude and practice regarding pill and condom use among university students.
      METHODS: The inquiry was developed in Campinas, a city in Southeastern Brazil, in
      2006. A total of 295 adolescent newcomers to a public university answered a
      structured questionnaire and Levenson's multidimensional locus of control scale.
      The scores of the dimensions of locus of control were calculated and Spearman's
      correlation coefficient was used to assess their correlation with knowledge and
      practice concerning pill and condom use. In order to assess the relationship
      between the dimensions of locus of control and sociodemographic variables and
      variables related to the individuals' sex life, Kruskal-Wallis and Mann-Whitney
      tests were used. RESULTS: Male adolescents had higher scores of powerful others
      externality when compared to female adolescents (p=0.01). Students living alone
      had lower internality (p=0.01). When locus of control was compared to condom use
      in the first intercourse, considering only the 102 students who informed the age
      of the beginning of sexual activity, greater internality was found among male
      adolescents who did not use condoms (p<0.05). When the locus of control scores
      were correlated with contraceptive knowledge and practice, it was found that the
      higher the powerful others externality locus, the lower the adequate use of
      contraceptive methods (r = -0.22, p=0.03). CONCLUSIONS: The powerful others
      externality locus influences the practice of contraceptive use in this group of
      adolescents.

PMID- 20140328
TI  - Youth map of the city of Santo Andre, Southeastern Brazil: an instrument to read
      social inequalities.
AB  - OBJECTIVE: To analyze social inequalities in young adults living in an urban area
      by mapping sociodemographic and economic data. METHODS: Using data from the 2000
      Demographic Census, 57 sociodemographic and economic variables of young adults
      aged from 15 to 24 years, living in the city of Santo Andre, Southeastern Brazil,
      were distributed among 43 areas of statistical data, corresponding to a division
      of the region into smaller districts. Data from the year 2000 were collected from
      the Santo Andre City Hall Department of Socioeconomic Indicators. Using factorial
      analysis, 13 variables were grouped in two factors - working conditions and life
      conditions, which distinguished areas that were similar to one another
      statistically. Cluster analysis of areas was performed, resulting in four social
      groups. RESULTS: The area that concentrated young adults with higher access to
      wealth was classified as central and that including individuals with lower access
      to wealth was classified as peripheral. Two intermediate areas could be
      identified, one closer to the highest access to wealth ('almost central') and
      another close to the lowest access to wealth ('almost peripheral').
      Discriminating variables were associated with work, migration, level of
      education, fertility, adolescent's position in the household, presence of spouse
      or partner, living conditions and assets owned. CONCLUSIONS: Differences among
      social groups revealed important inequalities among young adults who live, study
      and/or work in the city, which will contribute to the planning of public social
      policies aimed at these groups.

PMID- 20140329
TI  - Intimate partner violence and alcohol consumption.
AB  - OBJECTIVE: To estimate the prevalence of intimate partner violence and alcohol
      consumption during episodes of violence. METHODS: Cross-sectional study with a
      multi-stage probability sample, representative of the Brazilian population.
      Sample was comprised of 1,445 men and women, married or cohabitating, interviewed
      between November 2005 and April 2006. Interviews were conducted in the
      interviewees' homes, using a standardized closed questionnaire. Rates of
      prevalence of intimate partner violence were estimated and chi-square tests were
      used to assess gender differences in this prevalence. RESULTS: General prevalence
      of intimate partner violence was 10.7% in men and 14.6% in women. Men consumed
      alcohol in 38.1% of cases and women in 9.2%. As regards perception of alcohol
      consumption by intimate partner, men reported their female partners consumed
      alcohol in 30.8% of episodes of violence, while women reported that their male
      partners consumed it in 44.6% of episodes. CONCLUSIONS: Women were more
      frequently involved in mild and serious episodes of violence (perpetration,
      victimization or both) than men. The fact that episodes of violence reported were
      four times more frequent in intoxicated men enables the assumption that
      prevention of intimate partner violence may be promoted by public policies aimed
      at reducing alcohol consumption.

PMID- 20140330
TI  - Delivering rapid HIV tests results after delivery: a threat to breastfeeding at
      birth.
AB  - OBJECTIVE: To analyze factors associated with failure to breastfeed during the
      first hour of life, especially the influence of time of delivery of rapid HIV
      test results. METHODS: Cohort study, beginning with the administration of the
      rapid test and ending the first time the baby is breastfed. The study population
      included 944 delivering mothers that received rapid HIV testing with a negative
      result in five Baby-Friendly hospitals of the High-Risk Pregnancy System in the
      city of Rio de Janeiro, Southeastern Brazil, in 2006. Trained interviewers
      obtained data from laboratory and patient charts and interviewed mothers shortly
      after delivery. The influence of sociodemographic variables and antenatal and
      delivery care characteristics on failure to breastfeed during the first hour of
      life was determined through a multilevel model. RESULTS: Among participants,
      15.6% received the result of rapid HIV testing before delivery, 30.8% after
      delivery, and 53.6% had not yet been informed of their results at the time of the
      interview. Prevalence of failure to breastfeed in the first hour of life was
      52.5% (95% CI: 49.3;55.8). After adjustment, having received the result of rapid
      testing only after delivery doubled the risk of failing to breastfeed in the
      first hour (RR=2.06; 95% CI: 1.55;2.75). Other risk factors included nonwhite
      skin color, maternal income of up to one minimum wage, delivery by C-section,
      mother's lack of desire to breastfeed at birth, and mother's report that the
      hospital staff did not listen to her. Lack of knowledge of HIV testing from the
      mother's part was found to be a protective factor. CONCLUSIONS: The major risk
      factor for not breastfeeding in the first hour of life was failure to receive the
      results of rapid HIV testing prior to delivery. HIV testing should be made widely
      available during antenatal care; rapid testing should be performed upon
      admission, only when indicated, and with active search and prompt delivery of
      results to expecting mothers.

PMID- 20140331
TI  - Factors associated with cesarean sections in Brazilian hospitals.
AB  - OBJECTIVE: To assess the prevalence of cesarean sections in Brazilian hospitals.
      METHODS: A cross-sectional study was carried out with data from the World Health
      Organization's Global Data System for Maternal and Perinatal Health, for the
      Brazilian states of Sao Paulo, Pernambuco and the Federal District. Data relating
      to 15,354 women who gave birth between September/2004 and March/2005 were
      analyzed, according to sociodemographic, reproductive, and hospital-related
      characteristics. Bivariate analyses - with calculations of the prevalence ratios
      and respective confidence intervals - and multivariate Poisson regression
      analyses were performed. RESULTS: The prevalence ratio of cesarean sections was
      significantly higher among older women, who were married/living with a partner
      and with higher body mass index. The following conditions during pregnancy or
      birth were associated with higher cesarean section prevalence ratio: parturient
      being diagnosed as HIV-positive, heavier weight and greater head circumference of
      the newborn, and more prenatal consultations. In regression analysis, the
      following variables showed direct association with the outcome: parturient being
      older and with higher schooling level, presence of hypertension/eclampsia,
      chronic condition or some other medical condition, newborn's greater head
      circumference, being primiparous, having had a cesarean in the last pregnancy and
      having received an epidural block or rachidian analgesic during labor. Although
      the proportion of cesareans was higher in hospitals with a high complexity index,
      the difference was not statistically significant, as well as for other
      characteristics of hospitals. CONCLUSIONS: The conditions of the pregnancy,
      newborn and the sociodemographic and reproductive characteristics of the
      parturient were independently associated with cesarean delivery. The hospital
      complexity index was not associated with cesarean delivery, probably due to the
      homogeneity of the hospital sample.

PMID- 20140332
TI  - Risk factors for cesarean section by category of health service.
AB  - OBJECTIVE: To analyze the rate of cesarean section and differences in risk
      factors by category of health service, either public or private. METHODS: A cross
      sectional study was carried out including all pregnant women in labor admitted to
      hospitals in the city of Rio Grande, Southern Brazil, between January 1 and
      December 31, 2007. A pre-coded and pre-tested questionnaire was used to collect
      on social, demographic, obstetric and newborn care information. Two regression
      models were constructed: one for public users and the other one for private ones.
      Poisson regression was used in each model in the multivariate analysis.
      Prevalence rates and 95% confidence intervals were calculated for each adjusted
      factor. RESULTS: The rate of cesarean section was 43% and 86% among public and
      private users. Sociodemographic factors and twin births have a more significant
      impact among public users as well as number of pregnancies (25% vs. 13% reduction
      in public and private users, respectively) and previous cesarean section (86% vs.
      24% increase in public and private users, respectively). Prenatal care visits and
      hospital admissions affected the outcome only in women users of public services.
      CONCLUSIONS: Cesarean section rates were high in both groups studied, but it was
      twice as high among women cared in the private sector. Associated factors differ
      in magnitude by category of service used.

PMID- 20140333
TI  - Physical activity during pregnancy and fetal outcomes: a case-control study.
AB  - OBJECTIVE: To investigate the relationship between physical activity during the
      second trimester pregnancy and low birth weight, preterm birth, and intrauterine
      growth restriction. METHODS: Case-control study including 273 low birth weight
      newborns and 546 controls carried out in the city of Sao Paulo, Southeastern
      Brazil, in 2005. Low birth weight cases were grouped into two subsamples: preterm
      birth (n=117) and intrauterine growth restriction (n=134), with their related
      controls. Information was collected by means of interviews with mothers shortly
      after birth and transcription of medical records. Data were analyzed using
      conditional multiple and hierarchical logistic regression. RESULTS: Light
      physical activity for over 7 hours per day was shown to be protective against low
      birth weight (adjusted OR=0.61; 95% CI 0.39-0.94) with a dose-response
      relationship (p-value for trend=0.026). A similar trend was found for
      intrauterine growth restriction (adjusted OR=0.51; 95% CI 0.26-0.97). Homemaking
      activities were associated as a protective factor for both low birth weight and
      preterm birth (p-value for trend=0.013 and 0.035, respectively). Leisure-time
      walking was found to be protective against preterm birth. CONCLUSIONS: Mild
      physical activity during the second trimester of pregnancy such as walking has an
      independent protective effect on low birth weight, preterm birth, and
      intrauterine growth restriction.

PMID- 20140334
TI  - Trends in hospital admission and infant mortality from diarrhea: Brazil, 1995
      2005.
AB  - OBJECTIVE: To analyze trends in hospitalization and mortality rates for diarrhea
      in children less than one year old. METHODS: An ecological time-series study,
      between 1995 and 2005, was performed for Brazil as a whole and for the state
      capitals. Secondary data from the Ministry of Health was utilized, obtained from
      the Hospital Information System and from the Mortality Information System. During
      the study period, 1,505,800 hospitalizations and 39,421 deaths from diarrhea were
      registered among children under one year. Polynomial regression models were used
      to analyze the trends in hospitalization and mortality rates. RESULTS: There were
      reductions in hospitalizations and in infant deaths from diarrhea in the country
      and in 13 capitals. Eight capitals experienced reductions only in mortality from
      diarrhea, whereas three showed decreases only in hospitalization rates from
      diarrhea. In the combined analysis of diarrhea indicators and of general
      indicators, reductions in all the historical series were observed only in Brazil
      as a whole and in four capitals. CONCLUSIONS: The reduction in hospitalization
      and mortality rates from diarrhea observed through the time-series could be the
      result of prevention and control measures implemented.

PMID- 20140335
TI  - Blood donation prevalence and associated factors in Pelotas, Southern Brazil.
AB  - OBJECTIVE: To estimate the prevalence of blood donation and factors associated.
      METHODS: A cross-sectional study was carried out with a representative sample of
      2,986 individuals, aged 20 or more, in the municipality of Pelotas, Southern
      Brazil, in 2007. Three outcomes were considered: ever donating blood, donation
      during in the previous year and frequent donation pattern (at least two donations
      in the previous year). Each outcome was analyzed according to demographic,
      socioeconomic and health factors, exposure to blood donation publicity campaigns
      and whether the donor had a relative or friend who donated blood. The crude and
      multivariable analyses were performed using Poisson's regression, adjusted for
      sample design effect. RESULTS: Blood donation prevalence - ever, in the previous
      year and a frequent donation pattern - were 32%, 7.7% and 3.6%, respectively.
      Blood donation was more prevalent among males and increased in accordance with
      the economic level and health self-perception. The prevalence of ever donating
      blood was higher in the 50 to 65 years age group; in the previous year, it was
      higher among younger people (20 to 29 years); frequent donation was more
      prevalent in the 30 to 49 group. There was no association of the outcomes with
      skin color, marital status, religion, having a relative or friend who donates or
      knowing about publicity campaigns. CONCLUSIONS: Blood donation was more prevalent
      in men and in those who have better self-perception of health and a higher
      economic level. Campaigns encouraging blood donation should diversify the donor
      profile for reaching those groups of people who are less inclined to donate
      blood.

PMID- 20140336
TI  - Impact on human health of particulate matter emitted from burnings in the
      Brazilian Amazon region.
AB  - OBJECTIVE: To analyze the impact on human health of exposure to particulate
      matter emitted from burnings in the Brazilian Amazon region. METHODS: This was an
      ecological study using an environmental exposure indicator presented as the
      percentage of annual hours (AH%) of PM2.5 above 80 microg/m3. The outcome
      variables were the rates of hospitalization due to respiratory disease among
      children, the elderly and the intermediate age group, and due to childbirth. Data
      were obtained from the National Space Research Institute and the Ministry of
      Health for all of the microregions of the Brazilian Amazon region, for the years
      2004 and 2005. Multiple regression models for the outcome variables in relation
      to the predictive variable AH% of PM2.5 above 80 microg/m3 were analyzed. The
      Human Development Index (HDI) and mean number of complete blood counts per 100
      inhabitants in the Brazilian Amazon region were the control variables in the
      regression analyses. RESULTS: The association of the exposure indicator (AH%) was
      higher for the elderly than for other age groups (beta = 0.10). For each 1%
      increase in the exposure indicator there was an increase of 8% in child
      hospitalization, 10% in hospitalization of the elderly, and 5% for the
      intermediate age group, even after controlling for HDI and mean number of
      complete blood counts. No association was found between the AH% and
      hospitalization due to childbirth. CONCLUSIONS: The indicator of atmospheric
      pollution showed an association with occurrences of respiratory diseases in the
      Brazilian Amazon region, especially in the more vulnerable age groups. This
      indicator may be used to assess the effects of forest burning on human health.

PMID- 20140337
TI  - Cultural adaptation and psychometric properties of Brazilian Need for Recovery
      Scale.
AB  - OBJECTIVE: To translate the Need for Recovery Scale (NFR) into Brazilian
      Portuguese and culturally adapt it and assess the stability, internal consistency
      and convergent validity of the Brazilian scale among industrial workers. METHODS:
      The translation process followed the guidelines for cultural adaptation of
      questionnaires including the steps of translation, synthesis, back translation,
      expert committee review, and pre-testing. The Brazilian Portuguese NFR, final
      version (Br-NFR) was assessed for stability (n=52) and internal consistency
      (n=192) and for convergent validity through simultaneous assessment with other
      instruments: the Borg Scale (n=59); the Chalder Fatigue Questionnaire (n=57) and
      3 subscales of the SF-36 (n=56). RESULTS: Stability and internal consistency met
      the criterion for a reliable measure (ICC=0.80 and Cronbach's alpha =0.87,
      respectively). The convergent validity between Br-NFR and other instruments also
      showed good results: Borg Scale (r= 0.64); Chalder Questionnaire (r= 0.67); SF-36
      subscales: vitality (r= -0.84), physical functioning (r= -0.54), and role
      physical (r= -0.47). CONCLUSIONS: The Br-NFR proved to be a reliable instrument
      to evaluate work-related fatigue symptoms in industrial workers. Furthermore, it
      showed significant and good correlations with well-established instruments such
      as the Borg Scale, the Chalder Questionnaire and SF-36 vitality subscale,
      supporting the validity of the Br-NFR.

PMID- 20140338
TI  - Validation of the Brazilian version of the 'Spanish Burnout Inventory' in
      teachers.
AB  - OBJECTIVE: To assess factorial validity and internal consistency of the Brazilian
      version of the 'Spanish Burnout Inventory' (SBI). METHODS: The translation
      process of the SBI into Brazilian Portuguese included translation, back
      translation, and semantic equivalence. A confirmatory factor analysis was carried
      out using a four-factor model, which was similar to the original SBI. The sample
      consisted of 714 teachers working in schools in the metropolitan area of the city
      of Porto Alegre, Southern Brazil, in 2008. The instrument comprises 20 items and
      four subscales: Enthusiasm towards job (5 items), Psychological exhaustion (4
      items), Indolence (6 items), and Guilt (5 items). The model was analyzed using
      LISREL 8. RESULTS: Goodness-of-Fit statistics showed that the hypothesized model
      had adequate fit: chi2(164) = 605.86 (p<0.000); Goodness-of-Fit Index = 0.92;
      Adjusted Goodness-of-Fit Index = 0.90; Root Mean Square Error of Approximation =
      0.062; Nonnormed Fit Index = 0.91; Comparative Fit Index = 0.92; and Parsimony
      Normed Fit Index = 0.77. Cronbach's alpha measures for all subscales were higher
      than 0.70. CONCLUSIONS: The study showed that the SBI has adequate factorial
      validity and internal consistency to assess burnout in Brazilian teachers.

PMID- 20140339
TI  - Time orientation and executive functions in the prediction of mortality in the
      elderly: Epidoso study.
AB  - OBJECTIVE: To analyze the predictive ability of a functional cognitive index of
      mortality in the elderly. METHODS: Cohort study performed with 1,667 elderly
      individuals aged more than 65 years and living in the city of Sao Paulo,
      Southeastern Brazil, between 1991 and 2001. Functional cognitive index was
      constructed from time orientation and executive functions (going shopping and
      taking medication), controlled by sociodemographic variables, life habits,
      morbidity, self-perception of health, hospitalization, edentulism and social
      support. Deaths occurred during this period were analyzed with family members in
      home interviews, notary public offices and records from the Fundacao Seade (State
      System of Data Analysis Foundation), until 2003. Crude and adjusted relative
      risks were calculated with their respective 95% confidence intervals, using
      bivariate and multiple analysis with Poisson regression and p<0.05. RESULTS: In
      the final multivariate model, the following independent risk factors were
      identified by the index: partial loss of time orientation or executive functions
      (RR=1.37; 95% CI: 1.03;1.83); total loss of orientation and partial loss of
      functions (RR=1.71; 95% CI: 1.24;2.37); partial loss of orientation and total
      loss of functions (RR=1.76; 95% CI: 1.35;2.28); and total loss of orientation and
      functions (RR=1.64; 95% CI: 1.30;2.06). As regards health conditions, the
      following were observed: hospitalization (RR=1.45; 95% CI: 1.22;1.73); diabetes
      (RR=1.20; 95% CI: 1.00;1.44); and total edentulism (RR=1.34; 95% CI: 1.09;1.66).
      Monthly contact with relatives was identified as a protective factor (RR=0.83;
      95% CI: 0.69;1.00). CONCLUSIONS: The Functional Cognitive Index can help
      clinicians and health planners to make decisions on strategies for follow-up and
      prevention of treatable causes of cognitive deficit and functional loss to reduce
      mortality in the elderly.

PMID- 20140340
TI  - Role of autonomy in self-assessment of health by the elderly.
AB  - OBJECTIVE: To understand the meanings attributed to self-assessment of health by
      the elderly. METHODS: Qualitative study performed with 17 elderly individuals (>
      70 years of age) of both sexes, living in the city of Bambui, Southeastern
      Brazil, in 2008. An anthropological approach based on the model of signs,
      meanings and actions, which associates individual actions, cultural codes and the
      macro-social context, was used. Semi-structured interviews were conducted,
      focusing on self-assessment of health, description of health as 'good' and 'poor'
      and the criteria used by the elderly to rate their own health. ANALYSIS OF
      RESULTS: The idea organizing reports associates self-assessment of health by the
      elderly with the 'participating in life' and 'being anchored in life' logics. The
      first logic has autonomy as its basic line of thinking, including the following
      categories: remaining active within advanced instrumental and functional
      abilities, being in charge of one's life (as opposed to being dependent on
      others), being able to solve problems and acting at will. The second logic unites
      the following categories: being able to interact, being engaged in meaningful
      relationships and being able to rely on family members, friends and neighbors.
      CONCLUSIONS: Health is understood by the elderly as having autonomy in the
      exercise of functional abilities required by society, such as the ability to meet
      family obligations and the ability to perform social roles. By defining their
      health as good or fair, the elderly individual is not characterized as someone
      free from diseases, but rather able to act over the environment.

PMID- 20140341
TI  - Home care as change of the technical-assistance model.
AB  - OBJECTIVE: To analyze home care practices of outpatient and hospital services and
      their constitution as a substitute healthcare network. METHODOLOGICAL PROCEDURES:
      A qualitative study was carried out using tracer methodology to analyze four
      outpatient home care services from the Municipal Health Department and one
      service from a philanthropic hospital in the municipality of Belo Horizonte,
      Southeastern Brazil, between 2005 and 2007. The following procedures were carried
      out: interviews with the home care services' managers and teams, analysis of
      documents and follow-up of cases, holding interviews with patients and
      caregivers. The analysis was guided by the analytical categories home care
      integration into the healthcare network and technical-assistance model. RESULTS:
      Home care implementation was preceded by a political-institutional decision, both
      with a rationalizing orientation, intending to promote cost reduction, and also
      with the aim of carrying out the technical-assistance rearrangement of the
      healthcare networks. These two types of orientation were found to be in conflict,
      which implies difficulties for conciliating interests of the different players
      involved in the network, and also the creation of shared management spaces. It
      was possible to identify technological innovation and families' autonomy in the
      implementation of the healthcare projects. The teams proved to be cohesive,
      constructing, in the daily routine, new forms of integrating different
      perspectives so as to transform the healthcare practices. Challenges were
      observed in the proposal of integrating the different substitutive healthcare
      services, as the home care services' capacity to change the technical-assistance
      model is limited. CONCLUSIONS: Home care has potential for constituting a
      substitutive network by producing new care modalities that cross the projects of
      users, family members, social network, and home care professionals. Home care as
      a substitute healthcare modality requires political, conceptual and operational
      sustainability, as well as recognition of the new arrangements and articulation
      of ongoing proposals.

PMID- 20140342
TI  - Actions of health group coordinators within the teaching/care network.
AB  - OBJECTIVE: To analyze the model for actions by health promotion group
      coordinators, in primary healthcare units with links to professional training.
      METHODOLOGICAL PROCEDURES: A qualitative study was carried out in the
      municipality of Florianopolis, Southern Brazil, in 2001. Four groups were
      evaluated, over a total of 24 sessions at primary healthcare units. Participant
      observation was performed to start the fieldwork. The reports were analyzed by
      means of the technique of enunciative-pragmatic discourse analysis. ANALYSIS OF
      RESULTS: The types of action among the coordinators that were congruent with the
      preventive model were: oppression, bench teaching, biologism and higienism,
      prescription of approaches, blame apportionment, infantilization, reduction of
      collective problems, denigration of group settings and use of monologue. The
      types of action consonant with the new promotion model were: facilitation of free
      expression and autonomy, empathetic communication, constructivism, receptiveness,
      active listening and promotion of overcoming of violence and alienation.
      CONCLUSIONS: The coordinators acted primarily by means of the preventive model,
      without using technical and theoretical resources that allude to group
      methodology in the field of healthcare. The actions within the preventive and new
      health promotion models that were identified reveal characteristics that are
      grounded in, respectively, the ethics of oppression/subordination of users and
      cooperation/acceptance of users as free and responsible for their choices and
      consequences.

PMID- 20140343
TI  - Exporting 'failure': why research from rich countries may not benefit the
      developing world.
AB  - The '10/90 gap' was first highlighted by the Global Forum for Health Research. It
      refers to the finding that 90% of worldwide medical research expenditure is
      targeted at problems affecting only 10% of the world's population. Applying
      research results from the rich world to the problems of the poor may be a
      tempting, potentially easy and convenient solution for this gap. This paper had
      the objective of presenting arguments that such an approach runs the risk of
      exporting failure. Health interventions that are shown to be effective in the
      specific context of a Western industrialized setting will not necessarily work in
      the developing world.

PMID- 20140344
TI  - Knowledge industry: a powerful mechanism.
AB  - The paper deals with the pharmaceutical industry's links to the knowledge
      industry, through powerful marketing strategies. With the aim of scientifically
      legitimizing its products, the pharmaceutical industry interferes with the
      production of medical knowledge. In the form of a mechanism for directing
      economic interests, it funds drug research, biases its results and stimulates the
      production and publication of scientific papers. This is a mechanism that
      threatens important ethical issues: it transforms the process of scientific
      legitimization into a marketing strategy, compromises the credibility of the
      process of constructing medical knowledge and encourages distortions of the
      criteria for evaluating the quality of scientific papers.

PMID- 20140345
TI  - [Changes in tuberculosis treatment].

PMID- 20140346
TI  - [Neglected diseases: the strategies of the Brazilian Ministry of Health].

PMID- 20140347
TI  - Scalp folliculitis with Demodex: innocent observer or pathogen?

PMID- 20140348
TI  - Biochemical association between essential trace elements and susceptibility to
      Leishmania major in BALB/c and C57BL/6 mice.
AB  - Several enzymes that contribute to immune system responses require zinc and
      copper as trace elements for their activity. We examined zinc and copper levels
      in two susceptible Balb/c mouse lines and resistant C57bl/6 mice infected with
      Leishmania major MRHO/IR/75/ER, a prevalent strain that causes cutaneous
      leishmaniasis in Iran. Serum Zn and Cu were determined by flame atomic absorption
      spectrophotometry. Higher Cu levels were found in infected C57bl/6 mice and
      higher Zn levels were found in infected Balb/c mice. Also, Cu/Zn ratios were
      increased in both the Balb/c and the C57bl/6 mice. We conclude that
      concentrations of essential trace elements vary during cutaneous leishmaniasis
      infection and that this variation is associated with susceptibility/resistance to
      Leishmania major in Balb/c and C57bl/6 mice. We detected Zn deficiency in the
      plasma of infected Balb/c mice; possibly, therapeutic administration of Zn would
      be useful for treating this form of leishmaniasis. Increases in Cu level might
      increase resistance to leishmaniasis. Based on our findings, the Cu/Zn ratio
      could be a useful marker for the pathophysiology of leishmaniasis.

PMID- 20140349
TI  - Brucella melitensis: a rarely suspected cause of infections of genitalia and the
      lower urinary tract.
AB  - We examined the clinical presentation and outcome of Brucellar infections of
      genitalia and the lower urinary tract through a review of the medical records of
      10 cases of male patients with brucellar infections of the genitalia and lower
      urinary tract. The mean age of the patients with brucellosis was 49.2, (median
      52, range 15-77 years). Eleven out of 17 patients were rural residents, 15
      reported that they might have consumed unpasteurized dairy products, and four
      reported occupational exposure. Symptoms onset was acute in almost all cases.
      Scrotal pain, epidedimal swelling and fever were the most common symptoms. The
      Wright test was positive in 13 patients, while Brucella sp. was isolated from
      blood cultures in six cases. Only two patients were found with abnormal liver
      ultrasonography. All patients underwent treatment with doxycycline and
      aminoglycoside for seven days and doxycycline alone for two months. Most of them
      responded to antibiotic therapy with rapid regression of symptoms. One patient
      failed to respond to therapy and presented necrotizing orchitis, as well as
      abscesses, which required orchectomy. Brucellar infections of the genitalia and
      lower urinary tract have no specific clinical presentation; the usual laboratory
      examination is not sufficient to diagnose this kind of infection, therefore it
      could easily be misdiagnosed. An analytical medical history (including overall
      dietary habits and recent consumption of non-pasteurized dairy products) could
      indicate Brucellosis as would the persistence of symptoms despite a one-week
      antibiotic treatment. In general, patients afflicted by brucellar
      epididymoorchitis respond to Brucellosis antibiotic therapy, except for some rare
      cases that present necrotizing orchitis and require surgical treatment.

PMID- 20140350
TI  - Antimicrobial susceptibility of gram-positive bacteria isolated in Brazilian
      hospitals participating in the SENTRY Program (2005-2008).
AB  - We report the antimicrobial susceptibility patterns of the most frequently
      isolated Gram-positive bacteria in the Brazilian hospitals participating in the
      SENTRY Antimicrobial Surveillance Program. The strains were consecutively
      collected (one per patient) between January 2005 and September 2008 and
      susceptibility tested by reference broth microdilution methods at the JMI
      Laboratories (North Liberty, Iowa, USA). A total of 3,907 Gram-positive cocci
      were analyzed. The Gram-positive organisms most frequently isolated from
      bloodstream infections were Staphylococcus aureus (2,218 strains; 20.2% of
      total), coagulase-negative staphylococci (CoNS; 812 strains [14.7%]), and
      Enterococcus spp. (754 strains; 5.0%). S. aureus ranked first (28.1%) and
      Enterococcus faecalis ranked 7th (4.5%) among cases of skin and soft tissue
      infections. S. aureus was also the second most frequently isolated pathogen from
      patients with lower respiratory tract infections (24.9% of cases) after
      Pseudomonas aeruginosa (30.5%). Resistance to oxacillin was observed in 31.0% of
      S. aureus and the vast majority of oxacillin-resistant (MRSA) strains were also
      resistant to clindamycin, ciprofloxacin and levofloxacin. Vancomycin, linezolid
      and daptomycin were all very active against S. aureus strains tested (>99.9
      100.0% susceptible), but daptomycin (MIC(50), 0.25 g/mL and MIC(90), 0.5 g/mL)
      was four- to eight-fold more potent than vancomycin (MIC(50) and MIC(90) of 1
      g/mL) and linezolid (MIC(50), 1 g/mL and MIC(90), 2 g/mL). Vancomycin resistance
      increased significantly among enterococci during the study period, but it was
      restrict to only one medical center until 2007 and emerged in a second medical
      center in 2008. Daptomycin was the most active antimicrobial tested against
      enterococci in general (100.0% susceptible), followed by linezolid (99.9%
      susceptible), ampicillin (87.4%) and vancomycin (84.6%). In conclusion,
      daptomycin and linezolid showed excellent in vitro activity against contemporary
      Gram-positive organisms (3,907) collected in Brazilian hospitals monitored by the
      SENTRY Program, including MRSA, vancomycin-resistant enterococci (VRE) and other
      multi-drug-resistant organisms. Although vancomycin resistance rates in Brazil
      appears to be relatively low compared to those reported in the USA, VRE has
      emerged and rapidly disseminated in some Brazilian medical centers.

PMID- 20140351
TI  - Identifying and controlling a multiresistant Pseudomonas aeruginosa outbreak in a
      Latin-American cancer centre and its associated risk factors.
AB  - Pseudomonas aeruginosa is an important and frightening microorganism for patients
      suffering from cancer. Multiresistant P. aeruginosa (MRPA) may appear as a
      consequence of exposure to multiple antibiotics or from a breakdown in infection
      control practices. This article reports an MRPA outbreak in a cancer treatment
      centre and the consequent case control study. Mechanical ventilation was
      identified as being the main risk factor for developing MRPA colonisation or
      infection; molecular analysis confirmed the outbreak. A multifaceted strategy was
      adopted, involving reinforcing hand-washing practices, contact isolation,
      antibiotic restriction and suction devices for mechanically-ventilated patients.
      MRPA was controlled and the outbreak ended. Such strategy may be effective in
      controlling MRPS in low-resource environments amongst high risk cancer patients.

PMID- 20140352
TI  - Ineffectiveness for infants of immunization of mothers with pneumococcal capsular
      polysaccharide vaccine during pregnancy.
AB  - Pneumococcal (Pnc) carriage is associated with pneumococcal diseases. Breast
      feeding and maternal vaccination may be a useful approach to prevent pneumococcal
      infection in young infants. We examined the risk of Pnc carriage by infants at
      six months of age after pneumococcal polysaccharide vaccination of pregnant
      women. We selected 139 pregnant woman. The woman were randomly allocated to
      receive 23-valent polysaccharide vaccines during pregnancy (Group 1) after
      pregnancy (Group 2) or not receive any vaccine (Group 3). Nasopharyngeal swabs
      were collected from the infants at three and six months of age. The infants were
      evaluated monthly during the first six months. We included 47 mothers in Group 1,
      45 mothers in Group 2 and 47 mothers in Group 3. Forty-seven percent of the
      babies were exclusively breast fed until six months, 26% received both breast
      feeding and artificial feeding and 13% received only artificial feeding. Among
      those patients, 26% were colonized by Pnc at six months (12 from Group 1, 13 from
      Group 2, and 12 from Group 3). There was no significant difference in
      colonization between the three groups. Thirty percent of the children were
      colonized by a non-susceptible strain. We concluded that young infants (three
      months old) are already susceptible to pneumococcal carriage. Vaccination during
      pregnancy with a polysaccharide vaccine did not decrease Pnc colonization.

PMID- 20140353
TI  - Evaluation of the automated system Vitek2 for identification and antimicrobial
      susceptibility testing of Brazilian Gram-positive cocci strains.
AB  - Automated instruments offer many advantages for clinical laboratories.
      Nevertheless, they can have problems identifying and determining susceptibilities
      of some pathogens. Vitek2 (bioMerieux) is an automated system that was recently
      introduced to Brazil. We evaluated the performance of this equipment for
      Brazilian isolates that had been characterized using reference identification and
      antimicrobial susceptibility testing methods. Ninety-nine strains of Gram
      positive cocci from a local reference center collection were analyzed, consisting
      of 50 coagulase-negative Staphylococcus (CoNS) and 49 Enterococcus and related
      species. Vitek2 correctly identified 79.8% (79/99) of the isolates. Oxacillin
      resistance was detected in 76% (19/25) of resistant S. epidermidis strains and in
      88% (22/25) of other resistant CoNS species strains. Vancomycin resistance was
      detected in 100% (20/20) of resistant Enterococcus and related species strains.
      Vitek2 performed very well for the identification of S. epidermidis and non
      epidermidis staphylococci, and for the detection of vancomycin resistance in
      Enterococcus and related species. However, the system needs improvement in order
      to provide reliable results for the characterization of some CoNS species,
      identification of Enterococcus and related species and for detecting oxacillin
      resistance in CoNS.

PMID- 20140354
TI  - Nosocomial infections in Brazilian pediatric patients: using a decision tree to
      identify high mortality groups.
AB  - Nosocomial infections (NI) are frequent events with potentially lethal outcomes.
      We identified predictive factors for mortality related to NI and developed an
      algorithm for predicting that risk in order to improve hospital epidemiology and
      healthcare quality programs. We made a prospective cohort NI surveillance of all
      acute-care patients according to the National Nosocomial Infections Surveillance
      System guidelines since 1992, applying the Centers for Disease Control and
      Prevention 1988 definitions adapted to a Brazilian pediatric hospital. Thirty
      eight deaths considered to be related to NI were analyzed as the outcome variable
      for 754 patients with NI, whose survival time was taken into consideration. The
      predictive factors for mortality related to NI (p < 0.05 in the Cox regression
      model) were: invasive procedures and use of two or more antibiotics. The mean
      survival time was significantly shorter (p < 0.05 with the Kaplan-Meier method)
      for patients who suffered invasive procedures and for those who received two or
      more antibiotics. Applying a tree-structured survival analysis (TSSA), two groups
      with high mortality rates were identified: one group with time from admission to
      the first NI less than 11 days, received two or more antibiotics and suffered
      invasive procedures; the other group had the first NI between 12 and 22 days
      after admission and was subjected to invasive procedures. The possible modifiable
      factors to prevent mortality involve invasive devices and antibiotics. The TSSA
      approach is helpful to identify combinations of predictors and to guide
      protective actions to be taken in continuous-quality-improvement programs.

PMID- 20140355
TI  - Multidrug-resistant bacteria isolated from intensive-care-unit patient samples.
AB  - We examined epidemiological aspects and bacterial resistance patterns of bacteria
      isolated from intensive care unit (ICU) patient samples. During a 10 month period
      (from June 2006 to March 2007), 812 samples of blood, urine and cerebral spinal
      fluid (CSF) from 553 hospitalized patients, in ICU wards, including pediatric
      surgical, neonatal, adult surgical I, adult surgical II, general pediatrics,
      neurosurgical I, neurosurgical II, and internal medical, were collected. Minimum
      inhibitory concentration (MIC) of antibiotics for bacteria isolates was
      determined by the E-test method. The internal medicine ICU with 28.7% admissions
      gave the largest contribution. Coagulase negative staphylococci at frequencies of
      66.7 % and 36.5 % and E. coli at 20.9% were the bacteria most frequently isolated
      from the blood, CSF and urine samples, respectively. Samples taken from patients
      20-40 years old were the most frequent (32.2%), while the group of patients over
      sixty years contributed least (18.5%). Both Gram-positive and - negative isolates
      expressed resistance to most of the penicillins and cephalosporins tested.
      Combined therapy with vancomycin and meropenem or imipenem gave the most
      effective treatment against Gram-positive and Gram-negative isolates based on
      empirical therapy. High frequencies of multiresistant bacteria in ICUs warn us to
      administer a few effective antibiotics in our hospitals more wisely in order to
      reduce selective pressure on sensitive strains. This could help save the life of
      ICU patients and prevent of spread of resistant isolates in these critical wards.
      Due to continuous changes in antibacterial susceptibility patterns, periodical
      antibacterial sensitivity assessment in ICUs should be mandatory.

PMID- 20140356
TI  - In vitro fosfomycin activity in vancomycin-resistant Enterococcus faecalis.
AB  - Enterococci are part of the endogenous flora of human beings, are naturally
      resistant to several classes of antimicrobials, and are able to acquire
      resistance with relative ease. Currently the vancomycin-resistant enterococci are
      spread all over the world and treatment options for infections caused by it are
      often extremely limited. We assessed 193 vancomycin-resistant Enterococcus
      faecalis isolates collected from four different hospitals in Porto Alegre for
      their susceptibility to fosfomycin using the E-test and agar diffusion.
      Fosfomycin proved to be active in vitro against the great majority of isolates,
      indicating that it is a valid option in the treatment of these infections.

PMID- 20140357
TI  - Chronic hepatitis C virus in the state of Piaui, northeastern Brazil.
AB  - Knowledge of genotype distribution of hepatitis C virus (HCV) has clinical
      importance due to genotype 1 lower response to treatment compared with genotypes
      2 and 3. The goal of this survey was to describe clinical and laboratorial
      profiles of patients with chronic hepatitis C (CHC) in the State of Piaui, as
      well as to expand the overall awareness of the distribution of HCV genotyping in
      Northeast of Brazil. A retrospective cross-sectional study was carried out
      between April 1999 and August 2005. A total of 153 patients were included, 119
      (77.8%) males and 34 (22.2%) females; mean age = 48.01 +/- 9.11 years. We
      observed a homogeneous distribution between genotypes 1 (50.0%) and 3 (49.0%),
      while the most frequent subtype noticed was 3a (49.0%). The mean viral load among
      patients with subtype 1b (1,232,476 UI/mL) was significantly superior to the
      subtype 1a (391,204 UI/mL; p = 0.010) and to the subtype 3a (594,228 UI/mL; p =
      0.047). The average levels of gamma-glutamiltransferase of genotype 1 (144 mg/dL)
      had statistical differences when compared to genotype 3 (74 mg/dL; p = 0.014).
      Most patients showed mild to moderate degrees of histopathological
      necroinflammatory activity and hepatic fibrosis (79.0% and 56.2%, respectively).
      We concluded that most candidates to treatment of CHC in the State of Piaui
      presented with clinically stable hepatic illness; the distribution of genotypes 1
      and 3 was virtually homogeneous; and there was no significant demographic or
      clinical differences among genotypes or subtypes of HCV.

PMID- 20140358
TI  - Metabolic effects associated to the highly active antiretroviral therapy (HAART)
      in AIDS patients.
AB  - The aim of this study was to evaluate the metabolic abnormalities (dyslipidaemia
      and insulin resistance) associated with highly active antiretroviral therapy
      (HAART) in AIDS patients, treated in Campo Grande, Mato Grosso do Sul, Brazil.
      The patients were distributed in five different groups: Group 1, HIV-infected
      without antiretroviral therapy; Group 2, with Zidovudine, Lamivudine and
      Efavirenz or Nevirapine; Group 3, with Zidovudine, Lamivudine and Protease
      Inhibitor; Group 4, with Stavudine, Lamivudine and Efavirenz or Nevirapine; and
      Group 5, with Stavudine, Lamivudine and Protease Inhibitor. The lipid and glucose
      profile were determined and statistics comparison was made. The findings of this
      study showed significant statistics elevations of total cholesterol and
      triglycerides levels in patients of Groups 3, 4 and 5, when comparing to patients
      of Groups 1 and 2. Significant differences were not observed between the groups
      in the others parameters evaluated: Glucose, HDL cholesterol and LDL cholesterol.
      Comparing two drugs of same class (NNRTI) through the subgroups II-efavirenz and
      II-nevirapine, significant differences in the serum levels of total cholesterol,
      triglycerides and glucose favorable to the subgroup II-NVP were observed. These
      findings suggest that combinations including Protease Inhibitors and/or Stavudine
      could cause more adverse metabolic effects, and if possible, should be avoided in
      patients with others cardiovascular risk factors to prevent the precocious
      atherosclerosis in AIDS patients receiving HAART.

PMID- 20140359
TI  - Tuberculosis and AIDS co-morbidity in Brazil: linkage of the tuberculosis and
      AIDS databases.
AB  - This study evaluated differences in AIDS patients with and without tuberculosis
      (TB) in Espirito Santo State, Brazil. Standard regional AIDS (SINAN, SISCEL,
      SICLOM and SIM) and tuberculosis (SINAN) databases were used. TB and AIDS
      databases were linked using Reclink software, version 3, with SPSS software
      support to identify co-infected cases. Data from July 2000 to June 2006 in
      Espirito Santo State were linked. The results showed 3,523 adult AIDS cases and
      9,958 adult TB cases resulted in 430 co-infected patients, who were compared to
      1,290 AIDS patients who never developed TB. Among 430 co-infected patients, TB
      was diagnosed first in 223 (51.9%), AIDS was first in 44 (10.2%), and AIDS and TB
      were diagnosed concurrently in 163 (37.9%). Median age did not differ between co
      infected cases (36 years (interquartile range [IQR] 29-43) and non-co-infected
      cases (34 years; IQR 28-42). Pulmonary tuberculosis was diagnosed in 239 (55.6%);
      109 (25.3%) had extra-pulmonary TB and 82 (19.1%) had both presentations. In the
      final logistic regression model, living in a metropolitan area [Odds Ratio
      (OR)=1.43 (95% Confidence Interval (CI) 1.05-1.95)], education < 3 years [OR=3.03
      (95%CI 1.56-5.88)] and CD4 counts < 200/mm(3) [OR=1.14 (95%CI 1.09-1.18)] were
      associated with co-infection. This report emphasizes the significance of
      tuberculosis among AIDS cases in Brazil, and highlights the importance of
      evaluating secondary data for purposes of improving data quality and developing
      public health interventions.

PMID- 20140360
TI  - Comparison of immunoperoxidase and immunofluorescence assays for pp65
      cytomegalovirus antigen in immunocompromised patients.
AB  - We compared the pp65 antigen detection by an in house method (immunoperoxidase
      assay) and by a commercial kit (immunofluorescence assay) available for
      cytomegalovirus infection diagnosis in immunocompromised patients. Sixty-four
      blood samples were analyzed in duplicate for both techniques. Eight-six percent
      of the samples had concordant qualitative results. The discordant results
      occurred more frequently in samples with low quantity of positive cells. There
      were no significant differences with qualitative and quantitative results of the
      methods.

PMID- 20140361
TI  - Transverse myelitis associated to HCV infection.
AB  - Complications involving the central nervous system in patients suffering from
      hepatitis C virus (HCV) infection have been rare. Among them, it appears the
      transverse myelitis, which has already been reported in likely association with
      HCV. This paper presents the case study of a 65-year-old woman who developed
      cervical transverse myelitis linked to chronic HCV infection and anti-HCV
      antibodies in the spinal fluid, being excluded other etiologies for transverse
      myelitis. Current evidence has reinforced the likely association between chronic
      HCV infection and transverse myelitis, especially as recurrent manifestations of
      the disease. These findings reveal the need for more searching to establish the
      causal relationship between transverse myelitis and hepatitis C.

PMID- 20140362
TI  - Primary nodular hepatic tuberculosis mimicking hepatic neoplasia in an
      immunocompetent host.
AB  - We present and describe a case of nodular primary hepatic tuberculosis mimicking
      hepatic neoplasia in an immunocompetent host. This particularly rare
      presentation, associated with unspecific imaging, laboratory and clinical
      findings and relatively unspecific microbiological results make diagnosis
      extremely difficult, usually requiring surgical intervention.

PMID- 20140363
TI  - Delayed diagnosis of multibacillary leprosy: a report of eight cases.
AB  - Leprosy is an important public health problem in Brazil. However, this disease is
      still poorly diagnosed in its early stages, leading to permanent disability and
      disfigurement. We examined eight patients with clinical and histological
      diagnosis of multibacillary leprosy who were being treated for other diseases for
      about three years without clinical hypothesis of leprosy. These cases illustrate
      the importance of medical education and public information about leprosy's signs
      and symptoms for prompt recognition and treatment, which are necessary to prevent
      permanent disabilities and eradicate the disease.

PMID- 20140364
TI  - Agranulocytosis induced by multidrug therapy in leprosy treatment: a case report.
AB  - Multidrug therapy (WHO/MDT) in multibacillary leprosy consists of treatment with
      rifampicin, dapsone and clofazimine. However, adverse effects can cause the
      patient to abandon treatment. We report on a patient who presented
      agranulocytosis and hemolytic anemia associated with this treatment regime. We
      also examined the importance of laboratory exams for diagnosis and follow-up of
      the patient, and for early detection of adverse effects,with a view to improving
      adhesion to treatment and contributing to the eradication of Hansen's disease as
      a public health issue.

PMID- 20140365
TI  - Inhibition of Trypanosoma cruzi proline racemase affects host-parasite
      interactions and the outcome of in vitro infection.
AB  - Proline racemase is an important enzyme of Trypanosoma cruzi and has been shown
      to be an effective mitogen for B cells, thus contributing to the parasite's
      immune evasion and persistence in the human host. Recombinant epimastigote
      parasites overexpressing TcPRAC genes coding for proline racemase present an
      augmented ability to differentiate into metacyclic infective forms and
      subsequently penetrate host-cells in vitro. Here we demonstrate that both anti T.
      cruzi proline racemase antibodies and the specific proline racemase inhibitor
      pyrrole-2-carboxylic acid significantly affect parasite infection of Vero cells
      in vitro. This inhibitor also hampers T. cruzi intracellular differentiation.

PMID- 20140366
TI  - Absence of Fas-L aggravates renal injury in acute Trypanosoma cruzi infection.
AB  - Trypanosoma cruzi infection induces diverse alterations in immunocompetent cells
      and organs, myocarditis and congestive heart failure. However, the physiological
      network of disturbances imposed by the infection has not been addressed
      thoroughly. Regarding myocarditis induced by the infection, we observed in our
      previous work that Fas-L-/- mice (gld/gld) have very mild inflammatory
      infiltration when compared to BALB/c mice. However, all mice from both lineages
      die in the early acute phase. Therefore, in this work we studied the
      physiological connection relating arterial pressure, renal function/damage and
      cardiac insufficiency as causes of death. Our results show that a broader set of
      dysfunctions that could be classified as a cardio/anaemic/renal syndrome is more
      likely responsible for cardiac failure and death in both lineages. However,
      gld/gld mice had very early glomerular deposition of IgM and a more intense renal
      inflammatory response with reduced renal filtration, which is probably
      responsible for the premature death in the absence of significant myocarditis in
      gld/gld.

PMID- 20140367
TI  - Morphological study of the eggs and nymphs of Triatoma dimidiata (Latreille,
      1811) observed by light and scanning electron microscopy (Hemiptera: Reduviidae:
      Triatominae).
AB  - Eggs and nymphs of Triatoma dimidiata were described using both light and
      scanning electron microscopy. The egg body and operculum have an exochorion
      formed by irregular juxtaposed polygonal cells; these cells are without sculpture
      and the majority of them are hexagonal in shape. The five instars of T.
      dimidiatacan be distinguished from each other by characteristics of the pre, meso
      and metanotum. The number of setiferous tubercles increases progressively among
      instars. The sulcus stridulatorium of 1st instar nymphs is amorphous, showing
      median parallel grooves; from the 2nd instar on the sulcus is, progressively,
      elongate, deep and posteriorly pointed with stretched parallel grooves. All
      instars have a trichobothrium on the apical 1/3 of segment II of the antenna. The
      opening of the Brindley's gland is on the mesopleura. Fifth instar nymphs have an
      apical ctenidium on the ventral surface of the fore tibia. Dorsal glabrous
      patches are found on the lateral 1/3 of abdomen. Bright oval patches are found on
      the ventral median line of the abdomen, from segment IV-VI; 1st instar nymphs
      lack these patches. Abdominal dorsal plates are present from the 1st-5th instars;
      the 1st instar also contains a rectangular plate in segment IX. From the 2nd
      instar on, variably-shaped plates are present on segments VII to IX. Morphometric
      data were also obtained and proved to be useful for distinguishing T. dimidiata
      instars.

PMID- 20140368
TI  - Gap junction reduction in cardiomyocytes following transforming growth factor
      beta treatment and Trypanosoma cruzi infection.
AB  - Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse
      conduction in the heart and are affected by transforming growth factor-beta (TGF
      beta). This cytokine increases during Trypanosoma cruzi infection, modulating
      fibrosis and the parasite cell cycle. We studied Cx43 expression in
      cardiomyocytes exposed or not to TGF-beta T. cruzi, or SB-431542, an inhibitor of
      TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts
      with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta
      signalling had been shown previously to be highly activated. We demonstrated that
      TGF-beta treatment induced disorganised gap junctions in non-infected
      cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A
      similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with
      high TGF-beta secretion. Both results were reversed if the cells were incubated
      with SB-431542. Similar tests were performed using human chronic chagasic
      patients and we confirmed a down-regulation of Cx43 expression, an altered
      distribution of plaques in the heart and a significant reduction in the number
      and length of Cx43 plaques, which correlated negatively with cardiomegaly. We
      conclude that elevated TGF-beta levels during T. cruzi infection promote heart
      fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse
      conduction and arrhythmia that characterise severe cardiopathy in Chagas disease.

PMID- 20140369
TI  - Dengue-2 infection and the induction of apoptosis in human primary monocytes.
AB  - Monocytes/macrophages are important targets for dengue virus (DENV) replication;
      they induce inflammatory mediators and are sources of viral dissemination in the
      initial phase of the disease. Apoptosis is an active process of cellular
      destruction genetically regulated, in which a complex enzymatic pathway is
      activated and may be trigged by many viral infections. Since the mechanisms of
      apoptotic induction in DENV-infected target cells are not yet defined, we
      investigated the virus-cell interaction using a model of primary human monocyte
      infection with DENV-2 with the aim of identifying apoptotic markers. Cultures
      analyzed by flow cytometry and confocal microscopy yielded DENV antigen positive
      cells with rates that peaked at the second day post infection (p.i.), decayed
      afterwards and produced the apoptosis-related cytokines TNF-alpha and IL-10.
      Phosphatidylserine, an early marker for apoptosis, was increased at the cell
      surface and the Fas death receptor was upregulated at the second day p.i. at
      significantly higher rates in DENV infected cell cultures than controls. However,
      no detectable changes were observed in the expression of the anti-apoptotic
      protein Bcl-2 in infected cultures. Our data support virus modulation of
      extrinsic apoptotic factors in the in vitro model of human monocyte DENV-2
      infection. DENV may be interfering in activation and death mechanisms by inducing
      apoptosis in target cells.

PMID- 20140370
TI  - A new approach for potential drug target discovery through in silico metabolic
      pathway analysis using Trypanosoma cruzi genome information.
AB  - The current drug options for the treatment of chronic Chagas disease have not
      been sufficient and high hopes have been placed on the use of genomic data from
      the human parasite Trypanosoma cruzi to identify new drug targets and develop
      appropriate treatments for both acute and chronic Chagas disease. However, the
      lack of a complete assembly of the genomic sequence and the presence of many
      predicted proteins with unknown or unsure functions has hampered our complete
      view of the parasite's metabolic pathways. Moreover, pinpointing new drug targets
      has proven to be more complex than anticipated and has revealed large holes in
      our understanding of metabolic pathways and their integrated regulation, not only
      for this parasite, but for many other similar pathogens. Using an in
      silicocomparative study on pathway annotation and searching for analogous and
      specific enzymes, we have been able to predict a considerable number of
      additional enzymatic functions in T. cruzi. Here we focus on the energetic
      pathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and
      lipid metabolism. We point out many enzymes that are analogous to those of the
      human host, which could be potential new therapeutic targets.

PMID- 20140371
TI  - The triatominae species of French Guiana (Heteroptera: Reduviidae).
AB  - An annotated list of the triatomine species present in French Guiana is given. It
      is based on field collections carried out between 1993-2008, museum collections
      and a literature review. Fourteen species, representing four tribes and six
      genera, are now known in this country and are illustrated (habitus). Three
      species are recorded from French Guiana for the first time: Cavernicola pilosa,
      Microtriatoma trinidadensis and Rhodnius paraensis. The two most common and
      widely distributed species are Panstrongylus geniculatus and Rhodnius pictipes.
      The presence of two species (Panstrongylus megistus and Triatoma maculata) could
      be fortuitous and requires confirmation. Also, the presence of Rhodnius prolixus
      is doubtful; while it was previously recorded in French Guiana, it was probably
      mistaken for R. robustus. A key for French Guiana's triatomine species is
      provided.

PMID- 20140373
TI  - Occurrence of hybrids and laboratory evidence of fertility among three species of
      the Phyllosoma complex (Hemiptera: Reduviidae) in Mexico.
AB  - In seven studied communities of Western Mexico, triatomine specimens were
      sympatrically collected, some with atypical morphological characteristics in
      contrast to pure specimens, which were presumed to be hybrids. More than 200
      specimens of Meccus pallidipennis and Meccus longipennis with brown-yellow
      markings on dorsal connexival segments were collected in Ahuacapan and Quitupan.
      In La Mesa, more than 60 specimens similar to Meccus picturatus in most
      morphological characteristics (including size) were collected, although they
      presented a largely yellowish corium like M. pallidipennis. Interfertility was
      proven between all of the studied wild hybrid specimens, as well as between all
      the experimental laboratory hybrids. Two different phenotypes (M. picturatus and
      M. longipennis) were obtained from crosses between M. picturatus x M. picturatus
      and M. longipennis x M. longipennis from the three studied localities in state of
      Nayarit as from La Mesita. Results support the hypothesis that the subspecific
      ranking of those triatomines may, therefore, be more appropriate because
      reproductive isolation has not been developed and complete interbreeding was
      recorded.

PMID- 20140372
TI  - Species composition and natural infectivity of anthropophilic Anopheles (Diptera:
      Culicidae) in the states of Cordoba and Antioquia, Northwestern Colombia.
AB  - Malaria is a serious health problem in the states of Cordoba and Antioquia,
      Northwestern Colombia, where 64.4% of total Colombian cases were reported in
      2007. Because little entomological information is available in this region, the
      aim of this work was to identify the Anopheles species composition and natural
      infectivity of mosquitoes distributed in seven localities with highest malaria
      transmission. A total of 1,768 Anopheles mosquitoes were collected using human
      landing catches from March 2007-July 2008. Ten species were identified; overall,
      Anopheles nuneztovari s.l. was the most widespread (62%) and showed the highest
      average human biting rates. There were six other species of the Nyssorhynchus
      subgenus: Anopheles albimanus (11.6%), Anopheles darlingi (9.8%), Anopheles
      braziliensis (6.6%), Anopheles triannulatus s.l. (3.5%), Anopheles albitarsis
      s.l. and Anopheles oswaldoi s.l. at < 1%; and three of the Anopheles subgenus:
      Anopheles punctimacula, Anopheles pseudopunctipennis s.l. and Anopheles
      neomaculipalpusat < 1% each. Two species from Cordoba, An. nuneztovari and An.
      darlingi, were found to be naturally infected by Plasmodium vivax VK247, as
      determined by ELISA and confirmed by nested PCR. All species were active indoors
      and outdoors. These results provide basic information for targeted vector control
      strategies in these localities.

PMID- 20140374
TI  - Cloning, expression and characterisation of an HtrA-like serine protease produced
      in vivo by Mycobacterium leprae.
AB  - Members of the high temperature requirement A (HtrA) family of chaperone
      proteases have been shown to play a role in bacterial pathogenesis. In a recent
      report, we demonstrated that the gene ML0176, which codes for a predicted HtrA
      like protease, a gene conserved in other species of mycobacteria, is transcribed
      by Mycobacterium leprae in human leprosy lesions. In the present study, the
      recombinant ML0176 protein was produced and its enzymatic properties
      investigated. M. lepraerecombinant ML0176 was able to hydrolyse a variety of
      synthetic and natural peptides. Similar to other HtrA proteins, this enzyme
      displayed maximum proteolytic activity at temperatures above 40 degrees C and was
      completely inactivated by aprotinin, a protease inhibitor with high selectivity
      for serine proteases. Finally, analysis of M. leprae ML0176 specificity suggested
      a broader cleavage preference than that of previously described HtrAs homologues.
      In summary, we have identified an HtrA-like protease in M. lepraethat may
      constitute a potential new target for the development of novel prophylactic
      and/or therapeutic strategies against mycobacterial infections.

PMID- 20140375
TI  - Clinical and laboratory status of patients with chronic Chagas disease living in
      a vector-controlled area in Minas Gerais, Brazil, before and nine years after
      aetiological treatment.
AB  - Twenty-eight Chagas disease patients (CD), 22 with the indeterminate clinical
      form (IND) and six with the cardiac or digestive form (CARD/DIG), were treated
      with benznidazole and underwent clinical and laboratorial analysis before (IND
      and CARD/DIG) and nine years after [patients after treatment (CDt), patients with
      the indeterminate clinical form at treatment onset (INDt) and with the cardiac or
      digestive form at treatment onset (CARD/DIGt)] treatment. The data demonstrate
      that 82.1% of CDt patients (23/28) remained clinically stable and 95.4% of the
      INDt (21/22) and 33.3% of the CARD/DIGt (2/6) patients showed unaltered physical
      and laboratorial examinations. The clinical evolution rate was 2%/year and was
      especially low in INDt patients (0.5%/year) relative to CARD/DIGt patients
      (7.4%/year). Positive haemoculture in treated patients was observed in 7.1% of
      the cases. None of the INDt (0/21) and 33.3% of the CARD/DIGt (2/6) patients
      displayed positive cultures. The PCR presented a positive rate significantly
      higher (85.2%, 23/27) than haemoculture and two samples from the same patient
      revealed the same result 57.7% of the patients. Conventional serology-ELISA on 16
      paired samples remained positive in all individuals. Semi-quantitative ELISA
      highlighted significant decreases in reactivity, particularly in INDt relative to
      IND. Non-conventional serology-FC-ALTA-IgG, after treatment, showed positive
      results in all sera and 22 paired samples examined at seven and nine years after
      treatment, demonstrated significantly lower reactivity, particularly in INDt
      patients. This study was retrospective in nature, had a low number of samples and
      lacked an intrinsic control group, but the data corroborate other results found
      in the literature. The data also demonstrate that, even though a cure has not
      been detected in the none-treated patients, the benefits for clinical evolution
      were selectively observed in the group of INDt patients and did not occur for
      CARD/DIGt patients.

PMID- 20140376
TI  - Dispersal and survival of Nyssomyia intermedia and Nyssomyia neivai (Diptera:
      Psychodidae: Phlebotominae) in a cutaneous leishmaniasis endemic area of the
      speleological province of the Ribeira Valley, state of Sao Paulo, Brazil.
AB  - The dispersal and survival of the phlebotomines Nyssomyia intermedia and
      Nyssomyia neivai (both implicated as vectors of the cutaneous leishmaniasis
      agent) in an endemic area was investigated using a capture-mark-release technique
      in five experiments from August-December 2003 in municipality of Iporanga, state
      of Sao Paulo, Brazil. A total of 1,749 males and 1,262 females of Ny. intermedia
      and 915 males and 411 females of Ny. neivai were marked and released during the
      five experiments. Recapture attempts were made using automatic light traps,
      aspiration in natural resting places and domestic animal shelters and Shannon
      traps. A total of 153 specimens (3.48%) were recaptured: 2.59% (78/3,011) for Ny.
      intermedia and 5.35% (71/1,326) for Ny. neivai. Both species were recaptured up
      to 144 h post-release, with the larger part of them recaptured within 48 h. The
      median dispersion distances for Ny. intermedia and Ny. neivai, respectively, were
      109 m and 100 m. The greatest dispersal range of Ny. intermedia was 180 m, while
      for Ny. neivai one female was recaptured in a pasture at 250 m and another in a
      pigsty at 520 m, showing a tendency to disperse to more open areas. The daily
      survival rates calculated based on regressions of the numbers of marked insects
      recaptured on the six successive days after release were 0.746 for males and
      0.575 for females of Ny. intermedia and 0.649 for both sexes of Ny. neivai. The
      size of the populations in the five months ranged from 8,332-725,085 for Ny.
      intermedia males, 2,193-104,490 for Ny. intermedia females, 1,687-350,122 for Ny.
      neivai males and 254-49,705 for Ny. neivai females.

PMID- 20140377
TI  - Surveillance of Chagas disease vectors in municipalities of the state of Ceara,
      Brazil.
AB  - The present study aimed to analyse the dwelling infestation rates and the
      distribution and natural Trypanosoma cruzi infection rates, among triatomines
      captured in the 13 municipalities of the state of Ceara. The records relating to
      the capture of intradomicile and peridomicile triatomines during the Chagas
      disease control program of 1998-2008 were available. Among the triatomines
      captured and in all of the municipalities studied, Triatoma brasiliensis
      presented the highest incidence in intradomicile and Triatoma pseudomaculata in
      peridomicile and some were positive for infection by T. cruzi. We emphasise that
      it is important to have sustainable epidemiological surveillance in the region,
      since when the control measures decreased, the incidence of T. pseudomaculata in
      intradomicile grew.

PMID- 20140378
TI  - Ecological niche modelling and differentiation between Rhodnius neglectus Lent,
      1954 and Rhodnius nasutus Stal, 1859 (Hemiptera: Reduviidae: Triatominae) in
      Brazil.
AB  - Ecological niche modelling was used to predict the potential geographical
      distribution of Rhodnius nasutus Stal and Rhodnius neglectus Lent, in Brazil and
      to investigate the niche divergence between these morphologically similar
      triatomine species. The distribution of R. neglectus covered mainly the cerrado
      of Central Brazil, but the prediction maps also revealed its occurrence in
      transitional areas within the caatinga, Pantanal and Amazon biomes. The potential
      distribution of R. nasutus covered the Northeastern Region of Brazil in the semi
      arid caatinga and the Maranhao babacu forests. Clear ecological niche differences
      between these species were observed. R. nasutus occurred more in warmer and drier
      areas than R. neglectus. In the principal component analysis PC1 was correlated
      with altitude and temperature (mainly temperature in the coldest and driest
      months) and PC2 with vegetation index and precipitation. The prediction maps
      support potential areas of co-occurrence for these species in the Maranhao babacu
      forests and in caatinga/cerrado transitional areas, mainly in state of Piaui.
      Entomologists engaged in Chagas disease vector surveillance should be aware that
      R. neglectus and R. nasutus can occur in the same localities of Northeastern
      Brazil. Thus, the identification of bugs in these areas should be improved by
      applying morphometrical and/or molecular methods.

PMID- 20140379
TI  - Bromeliad-inhabiting mosquitoes in an urban botanical garden of dengue endemic
      Rio de Janeiro--are bromeliads productive habitats for the invasive vectors Aedes
      aegypti and Aedes albopictus?
AB  - Immatures of both Aedes aegypti and Aedes albopictus have been found in water
      holding bromeliad axils in Brazil. Removal of these plants or their treatment
      with insecticides in public and private gardens have been undertaken during
      dengue outbreaks in Brazil despite uncertainty as to their importance as
      productive habitats for dengue vectors. From March 2005-February 2006, we sampled
      120 randomly selected bromeliads belonging to 10 species in a public garden less
      than 200 m from houses in a dengue-endemic neighborhood in Rio de Janeiro. A
      total of 2,816 mosquito larvae and pupae was collected, with an average of 5.87
      immatures per plant per collection. Culex (Microculex) pleuristriatus and Culex
      spp of the Ocellatus Group were the most abundant culicid species, found in all
      species of bromeliads; next in relative abundance were species of the genus
      Wyeomyia. Only two individuals of Ae. aegypti (0.07%) and five of Ae.
      albopictus(0.18%) were collected from bromeliads. By contrast, immatures of Ae.
      aegypti were found in manmade containers in nearly 5% of nearby houses. These
      results demonstrate that bromeliads are not important producers of Ae. aegypti
      and Ae. albopictus and, hence, should not be a focus for dengue control. However,
      the results of this study of only one year in a single area may not represent
      outcomes in other urban localities where bromeliads, Ae. aegypti and dengue
      coincide in more disturbed habitats.

PMID- 20140380
TI  - Zoonotic parasites associated with felines from the Patagonian Holocene.
AB  - Feline coprolites were examined for parasites with the aim of studying ancient
      infections that occurred in the Patagonian region during the Holocene period.
      Eggs compatible to Trichuris sp., Calodium sp., Eucoleus sp., Nematodirus sp.,
      Oesophagostomum sp. (Nematoda), Monoecocestus sp. (Cestoda) and Eimeria
      macusaniensis (Coccidia) were recovered from faecal samples. The results obtained
      from the analysis provide evidence of consumption by felids of the viscera of
      both rodents and camelids. This knowledge allows for improved explanations as to
      the distribution of parasitism and its significance to the health of humans and
      animals inhabiting the area under study during the Middle Holocene.

PMID- 20140381
TI  - The first report of the main vector of visceral leishmaniasis in America,
      Lutzomyia longipalpis (Lutz & Neiva) (Diptera: Psychodidae: Phlebotominae), in
      the state of Rio Grande do Sul, Brazil.
AB  - Visceral leishmaniasis (VL) is a widespread zoonosis in Brazil and, up to now,
      there has been no record of the main vector of its agent, Lutzomyia longipalpis,
      in the Southern Region. Due to the diagnosis of VL in a dog in October 2008 in
      the city of Sao Borja, in the southernmost Brazilian state of Rio Grande do Sul,
      a collection of phlebotomines was undertaken to detect the presence of the vector
      Lu. longipalpis. The captures were carried out with CDC light traps on three
      consecutive nights in 2008. A total of 39 specimens of Lu. longipalpis were
      captured, thereby increasing the knowledge of the geographical distribution of
      this important vector.

PMID- 20140382
TI  - Effect of untreated bed nets on blood-fed Phlebotomus argentipes in kala-azar
      endemic foci in Nepal and India.
AB  - Observational studies in the Indian subcontinent have shown that untreated nets
      may be protective against visceral leishmaniasis (VL). In this study, we
      evaluated the effect of untreated nets on the blood feeding rates of Phlebotomus
      argentipes as well as the human blood index (HBI) in VL endemic villages in India
      and Nepal. The study had a 'before and after intervention' design in 58
      households in six clusters. The use of untreated nets reduced the blood feeding
      rate by 85% (95% CI 76.5-91.1%) and the HBI by 42.2% (95% CI 11.1-62.5%). These
      results provide circumstantial evidence that untreated nets may provide some
      degree of personal protection against sand fly bites.

PMID- 20140383
TI  - Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role
      for toll-like receptor 9 (TLR9).
AB  - Toxoplasma gondii infection is an important mediator of ocular disease in Brazil
      more frequently than reported from elsewhere. Infection and pathology are
      characterized by a strong proinflammatory response which in mice is triggered by
      interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A
      powerful way to identify the role of TLRs in humans is to determine whether
      polymorphisms at these loci influence susceptibility to T. gondii-mediated
      pathologies. Here we report on a small family-based study (60 families; 68
      affected offspring) undertaken in Brazil which was powered for large effect sizes
      using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of
      markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association
      Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5; p
      corrected = 1.2 x 10-4] between the C allele (frequency = 0.424; odds ratio = 7;
      95% confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic
      retinochoroiditis in Brazil. This supports the hypothesis that direct interaction
      between T. gondii and TLR9 may trigger proinflammatory responses that lead to
      severe pathologies such as the ocular disease that is associated with this
      infection in Brazil.

PMID- 20140384
TI  - Association of Lutzomyia longipalpis (Diptera: Psychodidae) population density
      with climate variables in Montes Claros, an area of American visceral
      leishmaniasis transmission in the state of Minas Gerais, Brazil.
AB  - In the present paper, we evaluate the relationship between climate variables and
      population density of Lutzomyia longipalpis in Montes Claros, an area of active
      transmission of American visceral leishmaniasis (AVL) in Brazil. Entomological
      captures were performed in 10 selected districts of the city, between September
      2002-August 2003. A total of 773 specimens of L. longipalpiswere captured in the
      period and the population density could be associated with local climate
      variables (cumulative rainfall, average temperature and relative humidity)
      through a mathematical linear model with a determination coefficient (Rsqr) of
      0.752. Although based on an oversimplified statistical analysis, as far as the
      vector is concerned, this approach showed to be potentially useful as a starting
      point to guide control measures for AVL in Montes Claros.

PMID- 20140385
TI  - Further evaluation of an updated PCR assay for the detection of Schistosoma
      mansoni DNA in human stool samples.
AB  - A previously reported sensitive PCR assay for the detection of Schistosoma
      mansoni DNA was updated and evaluated. Changes in the DNA extraction method,
      including the use of a worldwide available commercial kit and the inclusion of
      additional quality control measures, increased the robustness of the test, as
      confirmed by the analysis of 67 faecal samples from an endemic area in Brazil.
      The PCR assay is at hand as a proven, reliable diagnostic test for the control of
      schistosomiasis in specific settings.

PMID- 20140386
TI  - Should reproductively isolated populations of Lutzomyia longipalpis sensu lato
      receive taxonomically valid names?
AB  - A group of 18 research workers involved in different aspects of the biology of
      Lutzomyia longipalpis discussed whether or not it is important to give
      taxonomically valid names to populations that have been defined by biological,
      biochemical and molecular methods to be reproductively isolated. The type
      material of this medically important species has been lost and because of this it
      was recommended that a colony should be established from insects captured in the
      region of the type area and that their description should serve as the basis for
      future descriptions. It was pointed out that there is a lack of uniformity in the
      naming of closely related American sand flies and that some of the differences
      between populations of Lu. longipalpis are greater than those between accepted
      species. The majority of the participants agreed that the populations that have
      been defined in the literature as sibling species should be named.

PMID- 20140387
TI  - [The CBC journal is at Medline / PubMed].

PMID- 20140388
TI  - [Epidemiologic study of mandible fractures in a public hospital of Sao Paulo].
AB  - OBJECTIVE: To analyze the frequency epidemiological description of mandibular
      fractures correlating gender, age, etiological factors, anatomic location, and
      types of fracture's traces. METHODS: A retrospective survey of the medical
      history of 883 patients with facial fractures, attended at the Buco-Maxilo-Facial
      Surgery and Traumatology Service of the Hospital Geral de Vila Penteado in Sao
      Paulo (Sao Paulo - Brazil), in a period of 3 years (from January 2004 to December
      2006). RESULTS: From 883 patients evaluated, 270 presented mandibular fracture
      (30,5%). The male gender was the most affected (76,7%) in the age of 20 to 29
      years (33,0%), the most frequent etiological factor was the car accident (35,2%),
      the body of the mandible was the most affected anatomic location (47,4%) and the
      single traces prevailed (76,7%). CONCLUSION: The majority of the fractures were
      simple, located in the body of the mandible, and higligted in males, aged from 20
      t0 29 years, and caused by car accident.

PMID- 20140389
TI  - [Risk factors for distant metastasis in head and neck cancer].
AB  - OBJECTIVE: To identify risk factors for the development of distant metastasis
      (MD) among patients with head and neck squamous cell carcinoma (SCC) surgically
      treated. METHODS: A retrospective study of 253 patients from January, 1997 to
      December, 2002 was performed. Out of them, 10 patients presented DM during the
      follow up. The following aspects were analyzed: gender, age, tumor primary site,
      TNM classification, cervical lymph node status, and the presence of extracapsular
      spread - gross or microscopic. RESULTS: The survival average for the patients
      with DM, after finishing the oncological treatment, was 16 months (standard
      deviation = 2.256). The presence of both gross extracapsular spread (Odd ratio =
      14.429) and the microscopic one (OR = 17.471) and the both the neck advanced
      pathological staging (OR = 4.409) and the primary tumor staging (RR = 2.929)
      presented statistical significance as risk fators for the occurrence of DM.
      CONCLUSION: The risk factors for DM were: microscopic and gross extracapsular
      spread, the pathological presence of positive neck lymph node and advanced primay
      tumor.

PMID- 20140390
TI  - [Thoracic trauma: analysis of 124 patients who underwent thoracotomy].
AB  - OBJECTIVE: To analyze patients who underwent thoracotomy for the treatment of
      chest trauma in the City of Manaus. METHODS: We performed a retrospective study
      through analyzed records in the two main reference hospitals for trauma adults in
      this city during a period of 5 years. We considered for this study the
      epidemiological data, causal agent, type of incision, anatomical classification
      score of trauma, prognostic factors and mortality. RESULTS: We analyzed 124
      patients who underwent thoracotomy with a mean age of 28 years. Stab wounds were
      the most common casual agent (68%). The main indication for thoracotomy was
      massive hemothorax with 50.7% of cases, followed by cardiogenic or hypovolemic
      shock with 48.4%. There were 28 deaths (20.6%). Patients with vena cava injuries
      (5 patients) and aorta lesions (2 patients) had 100% mortality rate. There was a
      higher mortality in patients with major index of trauma (p = 0004), and largest
      quantity of blood transfused (p = 0090). CONCLUSION: Thoracic trauma patients
      submitted to exploratory thoracotomy were young, males and victims of stab wound
      trauma. The most contributing death factors were the lethal anatomical score,
      more than 15 points, and the association with major vascular lesions, as the
      aorta and vena cava.

PMID- 20140391
TI  - [Local therapy for hepatocellular carcinoma as a bridge to liver
      transplantation].
AB  - OBJECTIVE: To analyze the results of pre-operative local therapy for
      hepatocellular carcinoma in patients who were subjected to liver transplantation.
      METHODS: Cadaveric and living-related liver transplants done in cirrotic patients
      with hepatocellular carcinoma within the Milan criteria were included. The
      nodules were analyzed according to its number and diameter before and after the
      institution of the local therapy and on the explant evaluation. RESULTS: 22
      patients with 31 nodules that measured 28.8+/-12 mm in diameter were included.
      They were subjected to 21 sessions of percutaneous ethanol injection and 29
      sessions of transarterial chemoembolization. After the local therapy, 29 nodules
      that measured 24.6+/-12 mm in diameter were detected. All of them were within the
      Milan criteria and there was no difference compared to the diameter before the
      treatment. The patients were subjected to 17 cadaveric and 5 living-related liver
      transplantations. In six cases the tumors exceeded the Milan criteria on the
      explant evaluation: 4 due to its number and 2 due to its diameter. Sixteen cases
      were within the criteria and there were 14 neoplastic nodules with 30+/-14 mm in
      diameter. In these cases no difference was observed compared to the diameter
      before and after the local therapy. CONCLUSION: Local therapy for hepatocellular
      carcinoma with percutaneous ethanol injection and transarterial chemoembolization
      partially controlled tumor evolution considering the Milan criteria in patients
      waiting for liver transplantation. Significant differences were observed in terms
      of the Milan criteria on pre-operative examination compared to the explant
      evaluation.

PMID- 20140392
TI  - [Laparoscopic treatment of liver cysts].
AB  - OBJECTIVE: The authors present their experience with the laparoscopic management
      of non-parasitic liver cysts. METHODS: During the period from May 2003 to August
      2006, thirteen patients with non-parasitic liver cysts underwent laparoscopic
      fenestration. Eleven patients were female (84.6%) and two (15.4%) were male. The
      average age at diagnosis was 48.3 years (range 35-72). The majority of patients
      presented with pain, discomfort, dyspepsia, or early satiety at diagnosis.
      Computed tomography scans were performed in all cases. The cysts were solitary in
      eleven patients (84.6%) and polycystic liver disease in two patients (15.4%). The
      average size of the solitary cysts was 11.3 cm (range 9.5-17 cm), and the
      polycystic liver disease was 10.6 cm (range 9.2-12.1 cm). Operation was indicated
      due to symptoms in all patients. The technique performed was laparoscopic cyst
      fenestration. RESULTS: Laparoscopic fenestration was completed in all patients.
      Mean operative time was 85 minutes (range 53-110). Intraoperative complications
      were not detected and there was no death. Postoperative complications were
      observed in two patients (15.4%). Bile leakage was present in one patient, and
      ascites in another patient. Both cases were treated conservatively. The average
      hospital stay was 3.5 days (range 2-9 days). Mean follow-up was 36 months. There
      was one asymptomatic recurrence (7.6%) in a patient with polycystic liver disease
      after two years of follow-up. CONCLUSION: Laparoscopic fenestration is the
      preferred method of treatment for non-parasitic liver cyst. This operation causes
      low morbidity and the recurrence is uncommon. Adequate selection of patients and
      the laparoscopic technique are important for the treatment.

PMID- 20140393
TI  - [Cytophotometric expression of tumor antigen markers Ki-67 and CD-34 in prostate
      adenocarcinoma].
AB  - OBJECTIVE: To quantify the percentage of immunostaining through the labeling
      index as well as the optical density of Ki-67 and CD34 in prostate adenocarcinoma
      and compare the results between markers. METHODS: Markers Ki-67 and CD34 were
      studied using immunohistochemistry in 34 cases of prostate adenocarcinoma from
      radical prostatectomies performed at the Hospital Regional do Gama in Brasilia,
      Brazil from 2000 through 2005. Those markers were quantified using the SAMBA 4000
      software - Automated Scanning Microscopic Analysis System - and the IMMUNO
      software in the analysis of the variables labeling index and optical density.
      Spearman's correlation coefficient was estimated in order to evaluate the
      association between the expression levels of the markers. For the comparison of
      lesion types, Student's paired t-test and the nonparametric Wilcoxon test were
      used. RESULTS: Of the 34 blocks referred for the study of the tumor markers, 15
      were positive for Ki-67, 34 showed CD34 expression, and 14 were positive for both
      markers. The median value for the labeling index of CD34 was 72.72%; the minimum
      was 5.14% and the maximum, 88.81%. The median for the Ki-67 labeling index was
      73.78%, while the minimum was 16.87%, and the maximum, 87.47%. The median value
      for the optical density of CD34 was 48.33, the minimum was 35.65 and the maximum,
      85.86. For the optical density of Ki-67, the median was 40.03, while the minimum
      and maximum values were 21.53 and 52.43, respectively. CONCLUSION: The
      cytophotometric expression of Ki-67 had a mean labeling index of 64.04%, and the
      mean CD34 labeling index was 61.64%. The cytophotometric expression of the mean
      optical density of Ki-67 was 39.49, while for CD34 it was 53.69. There was a
      significant difference between Ki-67 and CD34 immunostaining with respect to
      optical density (P=0.025); no significant difference occurred regarding labeling
      index (P=0.470).

PMID- 20140394
TI  - [Accelerated protocol of rehabilitation after anterior cruciate ligament
      reconstruction with patellar tendon- normative data].
AB  - OBJECTIVE: evaluate the gotten results of the accelerated protocol adapted to the
      clinic conditions in CLA post operatory patients. METHODS: 30 patients were
      selected and submitted to an isokynetic test at the pre operatory and 4 months
      post operatory. RESULTS: the isokinetics evaluations at the pre operatory
      presented: flexor peak torque 93% at 60 degrees /s and 97,3% at 180 degrees /s.
      Extensor 87,3% at 60 degrees /s and 94,7% at 180 degrees /s; power of the flexor
      muscles of 93,3% and extensors of 96,7%; the muscular work of the flexors was of
      91,7% and extensors of 90,3%; the flexor peak torque angle was at 28,7 degrees .
      At the extensor musculature the angle was at 62,2 degrees ; flexors eccentric
      peak torque of 78,3% and the extensors of 12,8%. With 4 months of post operatory
      the gotten results showed: flexor peak torque 95,4% at 60 degrees /s and 97,1%.
      at 180 degrees /s; extensor 70% at 60 degrees /s and 75,7%. at 180 degrees /s;
      power of the flexor muscles of 97,1% and extensors of 79,8%; the muscular work of
      the flexors was of 94,2% and extensors of 94,2%; flexors eccentric peak torque of
      84% and extensors of 24,2%; the flexor peak torque angle was at 27,3 degrees ; in
      extensor musculature the angle was at 61,7 degrees . CONCLUSION: showed that the
      patients treated with the adapted protocol presented similar results to the
      original protocol in relation to the muscular conditions.

PMID- 20140395
TI  - [Effect of ascorbic acid and hidrocortisone on intestinal anastomotic tension].
AB  - OBJECTIVE: The effects of vitamin C and hidrocortisone on anastomotic healing
      process are controversial. The objective of the present paper was to compare the
      jejunal anastomotic tension in different postoperative periods. METHODS: 40 male
      rats weighing 200 to 400 grams were submitted to laparotomy. The jejunum was
      transversally cut 10 cm from the duodenojejunal flexure, and subsequently
      anastomosed. The rats were divided into four groups (n=10). Group I - control,
      Group II - oral administration of vitamin C (100 mg/kg), Group III -
      intraperitoneal administration of hidrocortisone (10 mg/kg), and Group IV -
      administration of vitamin C and hidrocortisone at the above mentioned doses. The
      anastomotic resistance was determined by using bursting pressure test on the 5th
      and 21st postoperative days. RESULTS: The resistances of the groups with vitamin
      C, isolated or associated to hidrocortisone trend to be higher in both
      postoperative periods. However, the administration of intraperitoneal steroid did
      not change the resistance of murine jejunal anastomosis. CONCLUSION: The results
      of the present study suggest that vitamin C enhances the resistance of jejunal
      anastomosis in the rat.

PMID- 20140396
TI  - [Experimental model in rats for the development of pseudoarthrosis].
AB  - OBJECTIVE: We sought to describe a new model of pseudoarthrosis in rats free of
      pathogenic species (Rattus norvegicus albinus - SPF). METHODS: The animals were
      randomly distributed into two groups were used: Group 1 - Control (n =6); Group 2
      - Experimental (n =6). In the Control group an access to the femur followed by
      the synthesis of the muscular and skin layers was done. The Experimental group
      was submitted to osteotomy of the femur and a pedicle flap of the fascia lata was
      interposed between the segments resulting from the surgically induced fracture.
      The procedure was carried on with both alignment and approximation of the
      fractured bone through the use of mononylon thread introduced into holes created
      in the proximal and distal. RESULTS: Radiological and anatomopathological studies
      showed the absence of bone consolidation with persistence of fibro-osteoid tissue
      up to 120 days of follow-up. CONCLUSION: The experimental model is suitable for
      the development of a pseudoarthrosis in rats.

PMID- 20140397
TI  - [Management of renal trauma].
AB  - Trauma incidence is increasing nowadays. Kidney injuries occur in about 10% of
      patients with blunt or penetrating trauma, and those lesions add morbidity and
      mortality when not appropriate care is carried out. A literature review of the
      most recent papers was done by the authors to clarify diagnosis and final
      treatment. The correct management is a must to preserve and keep the kidney
      function, moreover, the quality of life after a trauma event.

PMID- 20140398
TI  - [Hemicorporectomy with double barreled wet colostomy: an extremely rare
      procedure].
AB  - The Hemicorporectomy associated to Double-barreled wet colostomy is a high
      complex and heroic procedure and is to be used only exceptionally, when it is the
      last resource for treating locally advanced pelvic diseases in the absence of
      evidences of distant metastasis. We retrospectively analyzed the surgical
      technical details and the results from a hemicorporectomy with double-barreled
      wet colostomy in a single surgical time in a case of epidermoide carcinoma from a
      coetaneous pressure ulcer.

PMID- 20140399
TI  - [Surgeons training: today as always?].
AB  - This paper proposes to discuss the training methodologies for young surgeons,
      considering the modern needs, by discussing their expectations and the reality of
      the surgeons' job market nowadays. Scientific and technological novelties, the
      huge amount of information imposed daily, managerial interventions and cost
      issues modified radically the activities of the surgeons, especially if compared
      to classical conceptions. Recent re-readings of the classical ethical postulates
      demand a new behavior of the doctors concerning the patients and the society per
      se. Contemporaneous social culture bring about individual expectations concerning
      quality of life and professional perspective issues. It becomes necessary to
      modify the training methods for surgeons to make them adequate to the need of
      continuous learning and adaptation to new technological instruments. They also
      should adapt to social interactions with the patients and the other health
      professionals that fit nowadays expectations. Those structural adaptations are
      fundamental to maintain the interest of the new professionals in the area of
      surgery.

PMID- 20140400
TI  - [Intestinal intussusception in young adults: literature review].
AB  - Although intussusception is the main cause of intestinal obstruction in the
      pediatric population, it is a rare condition in adults, and when it happens, the
      clinical characteristics differ a lot from the pediatric group. The purpose of
      this article is to report a case of a 16 years-old male that was seen at the
      Emergency Room of the University Hospital of Sao Paulo with an intestinal
      intussusception as the first clinical presentation of a Burkitt lymphoma. A
      literature review was carried out and relevant aspects of the case are discussed.

PMID- 20140401
TI  - [Laparoscopic resection of the left lateral segment of the liver in living donor
      liver transplantation].
AB  - Laparoscopic resection of the left lateral segment of the liver in donors of
      living liver transplantation. The authors present a case of laparoscopic
      resection of the left lateral segment of the liver in a donor of living liver
      transplantation. The procedure was done in six hours and the left lateral segment
      of the liver was removed through a 15 cm right subcostal incision. The patient
      was discharged on the 5th post-operative day. A 40 mL intrabdominal collection of
      bile was percutaneously drained guided by ultra-sonography. The drain was removed
      after five days. Afterwards, the patient had good recovery with no other
      complication.

PMID- 20140404
TI  - Comprehensive rehabilitation programmes in the chronic phase after severe brain
      injury: a systematic review.
AB  - OBJECTIVE: The aim of this study was to perform a systematic review of the
      effectiveness of comprehensive rehabilitation programmes for adults in the
      chronic phase after severe acquired brain injury. METHODS: PubMed, PsychINFO and
      PsychLit were searched for articles published between 1990 and 2008 and a quality
      assessment was performed. The comprehensive programmes were subdivided into
      neurobehavioral interventions, residential community reintegration and day
      treatment programmes. The extracted data included study characteristics, patient
      characteristics and intervention characteristics. RESULTS: Thirteen studies met
      pre-established criteria. Two studies were randomized controlled trials, 5 were
      controlled comparative studies and 6 were uncontrolled longitudinal cohort
      studies. Overall, their methodological quality was limited. The investigated
      programmes led to substantial improvement in daily life functioning and community
      integration of severe chronic brain injury patients, with lasting effects at
      follow-up. Day-treatment programmes had the highest level of evidence.
      CONCLUSION: Comprehensive rehabilitation programmes appear to be effective in
      terms of a reduction in psychosocial problems, a higher level of community
      integration and an increase in employment. Although this is the first review to
      differentiate between specific programmes, clear-cut clinical recommendations
      cannot yet be set out due to limited methodological quality and poor description
      of patient and intervention characteristics. Specific recommendations for future
      studies are given.

PMID- 20140405
TI  - Benefits of treatment theory in the design of explanatory trials: cognitive
      treatment of illness perception in chronic low back pain rehabilitation as an
      illustrative example.
AB  - BACKGROUND: Evidence-based treatment is not effective for all patients. Research
      must therefore be carried out to help clinicians to decide for whom and under
      what circumstances certain treatment is effective. Treatment theory can assist in
      designing research that will provide results on which clinical decision-making
      can be based. OBJECTIVE: To illustrate how treatment theory can be helpful in the
      design of explanatory trials that assist clinical decision-making. METHODS: The
      benefit of treatment theory was demonstrated by approaching the design of a
      clinical trial from two perspectives: one without the use of treatment theory and
      one with the explicit use of treatment theory. Evaluation of the effectiveness of
      cognitive treatment of illness perceptions for patients with chronic low back
      pain was used as an illustrative example. ISSUES: With treatment theory as the
      main focus, the intervention became the starting point for the design of an
      explanatory trial. Potentially relevant patient selection criteria, essential
      treatment components, the optimal choice of a control group and the selection of
      outcome measures were specified. CONCLUSION: This paper not only describes
      problems encountered in research on the effectiveness of treatment, but also ways
      in which to address these problems.

PMID- 20140406
TI  - Is transcutaneous peroneal stimulation beneficial to patients with chronic stroke
      using an ankle-foot orthosis? A within-subjects study of patients' satisfaction,
      walking speed and physical activity level.
AB  - OBJECTIVE: The aim of this study was to evaluate whether community-dwelling
      chronic stroke patients wearing an ankle-foot orthosis would benefit from
      changing to functional electrical stimulation of the peroneal nerve. METHODS: In
      26 community-dwelling chronic (> 6 months post-onset) patients after stroke,
      their ankle-foot orthosis was replaced by a surface-based functional electrical
      stimulation device (NESS L300). Comfortable walking speed over 10 m was measured
      at baseline with the ankle-foot orthosis and after 2 and 8 weeks with both ankle
      foot orthosis and functional electrical stimulation. The level of physical
      activity was assessed with a pedometer, and patients' satisfaction was assessed
      with a questionnaire at baseline and at week 8 regarding ankle-foot orthosis and
      functional electrical stimulation, respectively. RESULTS: Ankle-foot orthosis and
      functional electrical stimulation were equally effective with regard to walking
      speed and activity level. The participants were more satisfied with functional
      electrical stimulation than with their ankle-foot orthosis regarding the effort
      and stability of walking, quality of the gait pattern, walking distance, comfort
      of wearing and appearance of the device. CONCLUSION: The patients judged
      functional electrical stimulation superior to their ankle-foot orthosis, but
      measurements of walking speed and physical activity could not objectify the
      experienced benefits of functional electrical stimulation. Other outcome measures
      focusing on the stability and effort of ambulation may objectify the perceived
      benefits of functional electrical stimulation in community-dwelling chronic
      stroke patients.

PMID- 20140407
TI  - Effects of group-based versus individual-based exercise training on motor
      performance in children with developmental coordination disorder: a randomized
      controlled study.
AB  - OBJECTIVE: To compare the effects of group-based and individual-based motor skill
      training on motor performance in children with developmental coordination
      disorder. DESIGN: Randomized controlled pilot intervention study.
      SUBJECTS/PATIENTS: Twenty-three children (4 girls) with developmental
      coordination disorder (mean age (standard deviation (SD)) 8 years (1 year and 2
      months)). METHODS: Twelve children were randomly assigned to undergo a motor
      training programme once a week for 8 consecutive weeks in a group setting, and 11
      children received the same training on an individual basis during the same
      period. Each child was also instructed to perform home exercises on a daily
      basis. The Movement Assessment Battery for Children (MABC) was used to assess
      motor ability. Home exercise compliance and parental satisfaction with the
      programmes were also evaluated. RESULTS: A significant reduction in the MABC
      total impairment score was found following both group-based (mean -4.4 (SD 5.0),
      p = 0.003) and individual-based training (mean -5.2 (SD 5.1), p = 0.016).
      However, the change in total impairment score did not differ significantly
      between the 2 groups (p = 0.379). There was similarly no significant between
      group difference in home exercise compliance (p = 0.288) and parental
      satisfaction (p = 0.379). CONCLUSION: Group-based training produced similar gains
      in motor performance to individual-based training. Group-based training may be
      the preferred treatment option due to the associated cost savings.

PMID- 20140408
TI  - Rehabilitation using manual mobilization for thoracic kyphosis in elderly
      postmenopausal patients with osteoporosis.
AB  - OBJECTIVE: To explore the feasibility and effects of rehabilitation using manual
      mobilization of the thoracic spine in elderly female patients with osteoporosis.
      METHODS: Forty-eight postmenopausal patients with osteoporosis (age 76 -/+ 7
      years) were randomly assigned to 3 months rehabilitation (18 sessions including
      manual mobilization, taping and exercises, n = 29) or control (wait-list, n =
      19). The primary outcome was thoracic kyphosis degree (Spinal-Mouse). Secondary
      outcomes were back pain (visual analogue scale) and quality of life (Qualeffo
      41). Explanatory outcomes were compliance with rehabilitation, complications, and
      patients' and therapists' perceptions regarding the rehabilitation programme.
      RESULTS: Thoracic kyphosis improved significantly following rehabilitation
      compared with controls (intention-to-treat analysis, p = 0.017); and in patients
      who were compliant with rehabilitation (n = 15) compared with those who were non
      compliant (p = 0.002) and controls (p = 0.001). Mental health worsened slightly
      in the rehabilitation group (p = 0.029), but not significantly compared with
      controls. Neither patients nor physical therapists reported serious adverse
      effects. CONCLUSION: Three months of rehabilitation with manual mobilization can
      attenuate thoracic kyphosis in elderly patients with osteoporosis. Its impact on
      back pain and quality of life remains unclear and needs further investigation.

PMID- 20140409
TI  - Ultrasonographic guided botulinum toxin type A treatment for plantar fasciitis:
      an outcome-based investigation for treating pain and gait changes.
AB  - OBJECTIVE: To evaluate the effectiveness of ultrasonographic guided botulinum
      toxin type A injections into the plantar fascia to reduce pain and improve gait
      in patients with unilateral plantar fasciitis. DESIGN: A randomized double-blind
      control study. SUBJECTS: Fifty patients with chronic unilateral plantar fasciitis
      were recruited, and divided into experimental and control groups. METHODS:
      Subjects in the experimental group were injected with 50 units botulinum toxin
      type A, reconstituted with normal saline, into the plantar fascia under
      ultrasonographic guidance. Follow-up evaluations were made 3 weeks and 3 months
      after injection. The control group subjects were injected with normal saline
      under ultrasonographic guidance. Outcome measures included comparing scores from
      the visual analogue pain scale, changes in thickness of the plantar fascia and
      fat pad, and gait assessment including the maximal centre of pressure velocity
      during first step loading response. RESULTS: Visual analogue pain scale and
      plantar fascia thickness in the symptomatic foot decreased significantly, as
      noted at follow-up 3 weeks and 3 months after botulinum toxin type A injections
      (p < 0.001). However, the fat pad thickness remained unchanged. The centre of
      pressure velocity during loading response increased 3 months after injection (p <
      0.05). Outcome measures of the control group remained unchanged. CONCLUSION:
      Botulinum toxin type A is effective in the treatment of foot pain associated with
      plantar fasciitis and increases the centre of pressure velocity during loading
      response without inducing fat pad atrophy.

PMID- 20140410
TI  - A qualitative examination of wheelchair configuration for optimal mobility
      performance in wheelchair sports: a pilot study.
AB  - OBJECTIVE: To examine wheelchair athletes' perceptions of wheelchair
      configuration in relation to aspects of mobility performance. METHODS: Nine elite
      wheelchair athletes from wheelchair basketball, wheelchair rugby and wheelchair
      tennis were interviewed using a semi-structured format. Interview transcripts
      were analysed using an Interpretative Phenomenological Analysis, whereby emergent
      themes with common connections were identified and clustered into 3 superordinate
      themes: (i) performance indicators; (ii) principal areas of wheelchair
      configuration; and (iii) supplementary areas of wheelchair configuration.
      RESULTS: Participants revealed that stability was the most important contributor
      towards successful performance. Whilst there was some agreement amongst
      participants on how manipulating most areas of wheelchair configuration
      influenced performance, opinions were divided as to whether camber had a positive
      or negative effect on straight line performance. CONCLUSION: Experienced athletes
      seemed to display a good understanding of how modifying wheelchair configurations
      can affect sports performance, yet the methods offered for identifying optimal
      settings were extremely subjective. Therefore, future quantitative research into
      specific areas of configuration is imperative to identify these optimums and to
      inform athletes about the decisions they make when configuring a new sports
      wheelchair.

PMID- 20140411
TI  - Effects of functional electrical stimulation cycling exercise on bone mineral
      density loss in the early stages of spinal cord injury.
AB  - OBJECTIVE: To determine whether bone mineral density loss after spinal cord
      injury can be attenuated by an early intervention with functional electrical
      stimulation cycling exercises (FESCE) and to ascertain whether the effect
      persists after FESCE is discontinued. DESIGN: A prospective study. SUBJECTS:
      Twenty-four individuals with spinal cord injury, 26-52 days after spinal cord
      injury, were divided into FESCE or control groups. METHODS: FESCE was applied in
      the initial 3 months and then suspended in the subsequent 3 months. Bone mineral
      density in the femoral neck and distal femur was measured using dual energy X-ray
      absorptiometry before training, immediately after the initial 3 months of
      training, and at the end of the subsequent 3 months. RESULTS: The bone mineral
      density decrease rate in the distal femur in the FESCE group was significantly
      less than that in the control group during the initial 3 months. However, there
      was no significant difference in the subsequent 3 months. CONCLUSION: FESCE in
      the early stages of spinal cord injury can partly attenuate bone mineral density
      loss in the distal femur. However, bone mineral density loss in the distal femur
      cannot be ameliorated completely by FESCE. In addition, the effect on the
      attenuation of bone loss in the distal femur faded once FESCE was discontinued.

PMID- 20140412
TI  - Life satisfaction in younger individuals after stroke: different predisposing
      factors among men and women.
AB  - OBJECT: To describe self-reported life satisfaction of younger persons after
      stroke and to investigate differences between men and women and factors
      associated with life satisfaction. DESIGN: A cross-sectional study. METHODS:
      Subjects were all persons after stroke, aged 18-55 years, registered in the
      Swedish National Quality Register for Stroke Care. A questionnaire was completed
      by 1068 individuals 8-36 months after stroke. Perceived Life Satisfaction was
      measured with LiSat-9. RESULTS: Less than half of the participants were satisfied
      with life as a whole. For women, significant associations were found between not
      being satisfied with life as a whole and haemorrhage (odds ratio (OR) 4.00) as
      well as a deteriorated ability to concentrate (OR 2.11). For men, significant
      associations were found to be not having a significant other (OR 3.17), not
      working (OR 2.26) and deteriorated ability to concentrate (OR 2.04). CONCLUSION:
      There were different factors for being satisfied with life as a whole between men
      and women, indicating a need for a more gender-specific rehabilitation than is
      currently used. The impact that deteriorated ability to concentrate has on life
      satisfaction is an important finding that needs to be considered in the
      rehabilitation process of younger patients after stroke.

PMID- 20140413
TI  - Determinants of return to work following non life threatening acute orthopaedic
      trauma: a prospective cohort study.
AB  - OBJECTIVE: To determine factors associated with return to work following acute
      non-life-threatening orthopaedic trauma. DESIGN: Prospective cohort study.
      PARTICIPANTS: One hundred and sixty-eight participants were recruited and
      followed for 6 months. The study achieved 89% participant follow-up. METHODS:
      Baseline data were obtained by survey and medical record review. Participants
      were further surveyed at 2 weeks, 3 and 6 months post-injury. Logistic regression
      was used to examine the association between potential predictors and first return
      to work by these 3 time-points. RESULTS: Sixty-eight percent of participants
      returned to work within 6 months. Those who sustained isolated upper extremity
      injuries were more likely to return to work early. Significant positive
      determinants of return to work included a strong belief in recovery, the presence
      of an isolated injury, education to university level and self-employment.
      Determinants associated with non-return to work included the receipt of
      compensation, older age, pain attitudes and blue-collar work. The primary reason
      given for return to work was financial security. CONCLUSION: Demographic, injury,
      occupation and psychosocial factors were significant predictors of return to
      work. The relative importance of factors at different time-points suggests that
      return to work is a multifactorial process that involves the complex interaction
      of many factors in a time-dependent manner.

PMID- 20140414
TI  - Development and initial psychometric evaluation of an item bank created to
      measure upper extremity function in persons with stroke.
AB  - OBJECTIVE: To create and illustrate the development of a method to parsimoniously
      and hierarchically assess upper extremity function in persons after stroke.
      DESIGN: Data were analyzed using Rasch analysis. SETTING: Re-analysis of data
      from 8 studies involving persons after stroke. SUBJECTS: Over 4000 patients with
      stroke who participated in various studies in Montreal and elsewhere in Canada.
      METHODS: Data comprised 17 tests or indices of upper extremity function and
      health-related quality of life, for a total of 99 items related to upper
      extremity function. Tests and indices included, among others, the Box and Block
      Test, the Nine-Hole Peg Test and the Stroke Impact Scale. Data were collected at
      various times post-stroke from 3 days to 1 year. RESULTS: Once the data fit the
      model, a bank of items measuring upper extremity function with persons and items
      organized hierarchically by difficulty and ability in log units was produced.
      CONCLUSION: This bank forms the basis for eventual computer adaptive testing. The
      calibration of the items should be tested further psychometrically, as should the
      interpretation of the metric arising from using the item calibration to measure
      the upper extremity of individuals.

PMID- 20140415
TI  - Revised version of the ability for basic movement scale (ABMS II) as an early
      predictor of functioning related to activities of daily living in patients after
      stroke.
AB  - BACKGROUND: The objective of this study was to test the predictive validity of a
      new scale, the Revised Version of the Ability for Basic Movement Scale (ABMS II).
      METHODS: A total of 71 patients after stroke participated in this prospective
      study. In addition to the ABMS II score, age, limb paresis as measured by the
      Brunnstrom stage, and functional ability as measured by the Barthel Index were
      also selected as predictor variables. RESULTS: Pearson's correlation coefficient
      analysis showed that the state of functional ability according to the 4-week
      Barthel Index had significant positive correlations with total scores of ABMS II
      and Brunnstrom stage at all data collection time-points. The results of linear
      stepwise regression analysis indicated that the 'turn over from supine position'
      at the start of rehabilitation and 'remain sitting' items of ABMS II at 2 weeks
      after onset of the stroke, in addition to the 2-week Barthel Index and 2-week
      Brunnstrom stage, were significant predictors (88.9%) of functional ability at 4
      weeks after onset of stroke. CONCLUSION: This study provides evidence for the
      predictive value of the ABMS II with regard to functional ability in patients
      after stroke.

PMID- 20140416
TI  - A definition of disability emphasizing the interaction between individual and
      social aspects that existed among Scandinavian precursors of rehabilitation
      medicine as early as 1912.

PMID- 20140417
TI  - Graded exercise for chronic fatigue syndrome: too soon to dismiss reports of
      adverse reactions.

PMID- 20140418
TI  - Comments of the community-based rehabilitation Africa network regarding the
      special report from the international rehabilitation forum.

PMID- 20140419
TI  - The oldest haplogyne spider (Araneae: Plectreuridae), from the Middle Jurassic of
      China.
AB  - New fossil spiders (Arachnida: Araneae) from Middle Jurassic (ca. 165 Ma) strata
      of Daohugou, Inner Mongolia, China are described as Eoplectreurys gertschi gen.
      et sp. nov. and referred to the modern haplogyne family Plectreuridae. This small
      family is restricted to southwestern USA, Mexico, and the adjacent Caribbean area
      today and hitherto has only a sparse Cenozoic fossil record. The morphology of
      Eoplectreurys is remarkably similar to modern forms and thus demonstrates great
      evolutionary conservatism. This new discovery not only extends the fossil record
      of the family by at least 120 Ma to the Middle Jurassic but also supports the
      hypothesis of a different distribution of the family in the past than today and
      subsequent extinction over much of its former range.

PMID- 20140420
TI  - The recognition of mental health disorders and its association with psychiatric
      scepticism, knowledge of psychiatry, and the Big Five personality factors: an
      investigation using the overclaiming technique.
AB  - The present study examined the general public's ability to recognise mental
      health disorders and this ability's association with psychiatric scepticism,
      knowledge of psychiatry, and the Big Five personality factors. A total of 477
      members of the British general public completed an overclaiming scale, in which
      they were asked to rate the degree to which they believed 20 mental health
      disorders (of which five were foils designed to resemble real disorders) were
      real or fake. Participants also completed a novel scale measuring psychiatric
      scepticism, a single-item measure of knowledge of psychiatry, and a measure of
      the Big Five personality factors. Results showed that participants were
      significantly more likely to rate foils as fake disorders than real disorders. In
      addition, the difference between real and foil ratings was significantly
      predicted by knowledge of psychiatry, psychiatric scepticism, and the Big Five
      personality factors of agreeableness and openness to experience. These results
      are discussed in relation to the overclaiming technique as a novel method to
      study mental health literacy.

PMID- 20140421
TI  - Multiplane ultrasound approach to quantify pleural effusion at the bedside.
AB  - OBJECTIVE: To assess the accuracy of a multiplane ultrasound approach to measure
      pleural effusion volume (PEV), considering pleural effusion (PE) extension along
      the cephalocaudal axis and PE area. METHODS: Prospective study performed on 58
      critically ill patients with 102 PEs. Thoracic drainage was performed in 46
      patients (59 PEs) and lung computed tomography (CT) in 24 patients (43 PEs). PE
      was assessed using bedside lung ultrasound. Adjacent paravertebral intercostal
      spaces were examined, and ultrasound PEV was calculated by multiplying the
      paravertebral PE length by its area, measured at half the distance between the
      apical and caudal limits of the PE. RESULTS: Ultrasound PEV was compared to
      either the volume of the drained PE (59 PE) or PEV assessed on lung CT (43 PE).
      In patients with lung CT, the accuracy of this new method was compared to the
      accuracy of previous methods proposed for PEV measurement. Ultrasound PEV was
      tightly correlated with drained PEV (r = 0.84, p < 0.001) and with CT PEV (r =
      0.90, p < 0.001). The mean biases between ultrasound and actual volumes of PE
      were -33 ml when compared to drainage (limits of agreement -292 to +227 ml) and 
      53 ml when compared to CT (limits of agreement -303 to +198 ml). This new method
      was more accurate than previous methods to measure PEV. CONCLUSION: Using a
      multiplane approach increases the accuracy of lung ultrasound to measure the
      volume of large to small pleural effusions in critically ill patients.

PMID- 20140422
TI  - Surgical therapies of female stress urinary incontinence: experience in 228
      cases.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study is to compare the
      efficacy and safety of tension-free vaginal tape (TVT) with Marshall-Marchetti
      Krantz (MMK) procedure in stress urinary incontinence (SUI) treatment. METHODS:
      Two hundred twenty-eight patients were enrolled in this study. TVT procedure was
      performed in 105 cases, MMK procedure was performed in 81 cases, Chi-square test
      was used, and P < 0.01 was considered statistically significant. RESULTS: The
      short-term success rate was about 89% in MMK group. However, the success rate
      fell to 68.2% at 5 years and 32% at 10 years. The short-term cure rate of TVT
      procedure was about 90.0%, and the 5-year cure rate was 84.3%. CONCLUSIONS: The
      short-term cure rate in both groups was similar, but the long-term success rate
      of the MMK procedure decreased sharply with time. The TVT technique provides long
      term cure rates of over 84% with minimal complications. Patients who underwent
      TVT experienced shorter operation time, less blood loss, and less hospital stay.

PMID- 20140423
TI  - Inhibitory activity against the fish pathogen Lactococcus garvieae produced by
      Lactococcus lactis TW34, a lactic acid bacterium isolated from the intestinal
      tract of a Patagonian fish.
AB  - After enrichment of Odontesthes platensis intestinal contents, 53 lactic acid
      bacteria (LAB) were isolated. From the four isolates that showed inhibitory
      activity against Lactococcus garvieae 03/8460, strain TW34 was selected because
      it exerted the strongest inhibition. It also inhibited other Gram-positive
      bacteria, but not Gram-negative fish pathogens. Phenotypic and 16S rDNA
      phylogenetic analyses showed that TW34 belongs to Lactococcus lactis. In
      addition, TW34 showed to be sensitive to different antibiotics. The production of
      the inhibitory agent against L. garvieae was growth associated, and it was
      significantly influenced by the incubation temperature. The optimal temperature
      for the antimicrobial production was as low as 15 degrees C. Both acidification
      and hydrogen peroxide production were ruled out as the source of inhibition. In
      contrast, the antimicrobial activity was completely lost by treatment with
      proteolytic enzymes, which confirmed that the inhibitory substance was a
      bacteriocin. The bacteriocin was highly thermostable (121 degrees C for 15 min)
      and active between pH 3 and 11. It remained stable for up to 2 months when stored
      at 4 degrees C and up to 6 months at -20 degrees C. Our results suggest that the
      strain L. lactis TW34 could provide an alternative for lactococcosis control and
      therefore be considered for future challenge experiments with fish.

PMID- 20140424
TI  - The toxicokinetics of ketoprofen in Gyps coprotheres: toxicity due to zero-order
      metabolism.
AB  - In a safety study, Cape Griffon vultures (Gyps coprotheres) were dosed with
      ketoprofen at single doses of ~1 mg/kg (n = 5) and 5 mg/kg (n = 11). No toxicity
      was reported in the 1 mg/kg group, with the AUC(inf), V(z) and Cl being 10.42
      MUg/ml h, 0.37 l/kg and 0.10 l/h kg, respectively. Toxicity occurred in the 5
      mg/kg group, with 7 of the 11 birds dying. Clinical signs of toxicity included
      depression, loss of appetite and apparent coma. Animals died within 48 h of
      dosing. The AUC(inf), V(z) and Cl in the birds that survived were 52.26 MUg/ml h,
      0.45 l/kg and 0.10 l/h kg, respectively. The AUC(inf), V(z) and Cl in the birds
      those died were 207.90 MUg/ml h, 0.26 l/kg and 0.02 l/h kg, respectively. Based
      on the increase in the AUC(inf) and C(max) in the birds that died, we surmise
      that toxicity resulted from saturation of the metabolic process. While the exact
      metabolic pathway remains unknown in these vultures, we believe that toxicity may
      be due to pharmacogenomic differences in the cytochrome P450 pathway.

PMID- 20140425
TI  - Ambient particulate matter and preterm birth or birth weight: a review of the
      literature.
AB  - To review epidemiologic evidence on maternal exposure to particulate matter and
      adverse pregnancy outcomes, we performed a MEDLINE search of the literature up to
      June 2009. We considered all original studies published in English including
      information on total suspended particles (TSP), respirable (PM(10)) or fine
      (PM(2.5)) particles and the risk of preterm birth, low birth weight (LBW) or very
      low birth weight (VLBW) and small for gestational age (SGA). We identified a
      total of 30 papers, including 13 with information on preterm birth, 17 on LBW or
      VLBW, and 4 on SGA. Eight studies on preterm birth, 11 studies on LBW/VLBW and
      two studies on SGA reported some increased risk (by about 10-20%) in relation to
      exposure to PM; no meaningful associations was found in the remaining studies.
      However, even in studies reporting some excess risk, this was inconsistent across
      exposure levels and pregnancy periods. Epidemiologic studies on maternal exposure
      to PM during pregnancy thus do not provide convincing evidence of an association
      with the risk of preterm birth and LBW/VLBW and SGA. The excess risks, if any,
      are small, and it is unclear whether they are causal, due to misclassification of
      the exposure or some sources of bias/residual confounding.

PMID- 20140426
TI  - 2-(5-Benzoacridine)ethyl-p-toluenesulfonate as sensitive reagent for the
      determination of bile acids by HPLC with fluorescence detection and online
      atmospheric chemical ionization-mass spectrometric identification.
AB  - 2-(5-Benzoacridine)ethyl-p-toluenesulfonate (BAETS), a dual-sensitive probe, was
      reacted with bile acids in the presence of K(2)CO(3) catalyst in dimethyl
      sulfoxide (DMSO) solvent to give BAETS-bile acid derivatives. Derivatives
      exhibited intense fluorescence (FL) with an excitation maximum at lambda(ex) 270
      nm and an emission maximum at lambda(em) 510 nm. MS analysis using APCI-MS
      indicated that derivatives had excellent APCI-MS ionizability with percentage
      ionization delta values changing from 0 to 88.83% in aqueous acetonitrile and
      from 0 to 89.15% in aqueous methanol. The collision induced dissociation spectra
      of m/z [M + H](+) contained specific fragment ions at m/z [M + H-H(2)O](+), [M +
      H-2H(2)O](+), [M + H-3H(2)O](+), 347.3, and 290.1. Repeatability was good for LC
      separation of BAETS-bile acid derivatives with aqueous acetonitrile as mobile
      phase. The relative standard deviations (RSDs) of retention time and peak area at
      6.6 nmol mL(-1) levels with fluorescence detection (FL) were from 0.045 to 0.072%
      and from 2.16 to 2.73%, respectively. Excellent linear responses were observed,
      with regression coefficients >0.9995. The FL detection limits (S/N = 3) were in
      the range of 18.0-36.1 fmol. The online APCI-MS detection limits are in the range
      of 500-790 fmol (at a signal-to-noise ratio of 3).

PMID- 20140427
TI  - Olanzapine and pancytopenia with severe folate deficiency.

PMID- 20140428
TI  - Engineering of protein secretion in yeast: strategies and impact on protein
      production.
AB  - Yeasts combine the ease of genetic manipulation and fermentation of a
      microorganism with the capability to secrete and modify foreign proteins
      according to a general eukaryotic scheme. Their rapid growth, microbiological
      safety, and high-density fermentation in simplified medium have a high impact
      particularly in the large-scale industrial production of foreign proteins, where
      secretory expression is important for simplifying the downstream protein
      purification process. However, secretory expression of heterologous proteins in
      yeast is often subject to several bottlenecks that limit yield. Thus, many
      studies on yeast secretion systems have focused on the engineering of the
      fermentation process, vector systems, and host strains. Recently, strain
      engineering by genetic modification has been the most useful and effective method
      for overcoming the drawbacks in yeast secretion pathways. Such an approach is now
      being promoted strongly by current post-genomic technology and system biology
      tools. However, engineering of the yeast secretion system is complicated by the
      involvement of many cross-reacting factors. Tight interdependence of each of
      these factors makes genetic modification difficult. This indicates the necessity
      of developing a novel systematic modification strategy for genetic engineering of
      the yeast secretion system. This mini-review focuses on recent strategies and
      their advantages for systematic engineering of yeast strains for effective
      protein secretion.

PMID- 20140429
TI  - Clinical and imaging findings of systemic hyalinosis: two cases presenting with
      congenital arthrogryposis.
AB  - Systemic hyalinosis is a rare, multisystem, progressive, autosomal recessive
      disorder of connective tissue characterized by diffuse hyaline deposition in the
      skin, bone or viscera. Owing to its rarity and initial manifestations that
      resemble arthrogryposis congenital multiplexa, correct diagnosis can be elusive
      and often delayed. We present the computed tomography (CT) and whole-body (WB)
      magnetic resonance (MR) findings in two unrelated children with systemic
      hyalinosis who came to medical attention because of multiple joint contractures
      and limitation of motion in early infancy.

PMID- 20140430
TI  - The role of ultrasonography in the diagnosis of gluteal muscle contracture.
AB  - AIM: To evaluate the use of ultrasonography (US) in the diagnosis of gluteal
      muscle contracture (GMC) by analysis of its imaging characteristics. MATERIALS
      AND METHODS: Thirty-nine patients suspected of having GMC due to abnormal gait
      underwent pre-operative US. RESULTS: The diagnosis of GMC was confirmed by
      surgery in 27 patients. Six patients were diagnosed with congenital hip
      dysplasia, and the remaining six patients were diagnosed with sciatic nerve
      damage, post-poliomyelitis sequelae, and myasthenia gravis. For the patients with
      GMC, US showed muscle thinning and hyperechoic strips (specific for muscular
      contracture) in the muscles involved. In three patients with GMC, the strips were
      integrated into muscle bundles, demonstrating both strong and weak sonographic
      echoes. The sensitivity and specificity of the diagnosis of GMC using the
      presence of strips were 88.9% and 83.3%, respectively, and using muscle thinning,
      the sensitivity and specificity were 92.6% and 50%, respectively. The contracture
      strips, as measured by US, were significantly smaller than the actual
      measurements at the time of surgery, but there was a significant correlation
      between the two measurements (r = 0.814, P < 0.01). The highest detection rate of
      GMC by US was found in the gluteus maximus muscle (91.8%), and the lowest rate
      was found in the piriformis muscle (52.9%). CONCLUSION: Ultrasonography is a
      valuable tool for the diagnosis of GMC, especially for the detection of specific
      contracture strips in involved muscles. Its role in the pre-operative diagnosis
      of GMC also provides surgical planning that can guide subsequent treatment.

PMID- 20140431
TI  - HLA-A2-restricted T-cell epitopes specific for prostatic acid phosphatase.
AB  - Prostatic acid phosphatase (PAP) has been investigated as the target of several
      antigen-specific anti-prostate tumor vaccines. The goal of antigen-specific
      active immunotherapies targeting PAP would ideally be to elicit PAP-specific CD8+
      effector T cells. The identification of PAP-specific CD8+ T-cell epitopes should
      provide a means of monitoring the immunological efficacy of vaccines targeting
      PAP, and these epitopes might themselves be developed as vaccine antigens. In the
      current report, we hypothesized that PAP-specific epitopes might be identified by
      direct identification of pre-existing CD8+ T cells specific for HLA-A2-restricted
      peptides derived from PAP in the blood of HLA-A2-expressing individuals. 11
      nonamer peptides derived from the amino acid sequence of PAP were used as
      stimulator antigens in functional ELISPOT assays with peripheral blood
      mononuclear cells from 20 HLA-A2+ patients with prostate cancer or ten healthy
      blood donors. Peptide-specific T cells were frequently identified in both groups
      for three of the peptides, p18-26, p112-120, and p135-143. CD8+ T-cell clones
      specific for three peptides, p18-26, p112-120, and p299-307, confirmed that these
      are HLA-A2-restricted T-cell epitopes. Moreover, HLA-A2 transgenic mice immunized
      with a DNA vaccine encoding PAP developed epitope-specific responses for one or
      more of these three peptide epitopes. We propose that this method to first
      identify epitopes for which there are pre-existing epitope-specific T cells could
      be used to prioritize MHC class I-specific epitopes for other antigens. In
      addition, we propose that the epitopes identified here could be used to monitor
      immune responses in HLA-A2+ patients receiving vaccines targeting PAP to identify
      potentially therapeutic immune responses.

PMID- 20140433
TI  - Towards a duty of care for biodiversity.
AB  - The decline in biodiversity is a worldwide phenomenon, with current rates of
      species extinction more dramatic than any previously recorded. Habitat loss has
      been identified as the major cause of biodiversity decline. In this article we
      suggest that a statutory duty of care would complement the current mix of policy
      options for biodiversity conservation. Obstacles hindering the introduction of a
      statutory duty of care include linguistic ambiguity about the terms 'duty of
      care' and 'stewardship' and how they are applied in a natural resource management
      context, and the absence of a mechanism to guide its implementation. Drawing on
      international literature and key informant interviews we have articulated
      characteristics of duty of care to reduce linguistic ambiguity, and developed a
      framework for implementing a duty of care for biodiversity at the regional scale.
      The framework draws on key elements of the common law 'duty of care', the
      concepts of 'taking reasonable care' and 'avoiding foreseeable harm', in its
      logic. Core elements of the framework include desired outcomes for biodiversity,
      supported by current recommended practices. The focus on outcomes provides
      opportunities for the development of innovative management practices. The
      framework incorporates multiple pathways for the redress of non-compliance
      including tiered negative sanctions, and positive measures to encourage
      compliance. Importantly, the framework addresses the need for change and
      adaptation that is a necessary part of biodiversity management.

PMID- 20140432
TI  - Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in
      peripheral blood from paclitaxel hematotoxicity.
AB  - Bone marrow myelotoxicity is a major limitation of chemotherapy. While
      granulocyte colony stimulating factor (G-CSF) treatment is effective, alternative
      approaches to support hematopoietic recovery are sought. We previously found that
      a beta-glucan extract from maitake mushroom Grifola frondosa (MBG) enhanced
      colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow
      and human hematopoietic progenitor cells (HPC), stimulated G-CSF production and
      spared HPC from doxorubicin toxicity in vitro. This investigation assessed the
      effects of MBG on leukocyte recovery and granulocyte/monocyte function in vivo
      after dose intensive paclitaxel (Ptx) in a normal mouse. After a cumulative dose
      of Ptx (90-120 mg/kg) given to B6D2F1mice, daily oral MBG (4 or 6 mg/kg),
      intravenous G-CSF (80 microg/kg) or Ptx alone were compared for effects on the
      dynamics of leukocyte recovery in blood, CFU-GM activity in bone marrow and
      spleen, and granulocyte/monocyte production of reactive oxygen species (ROS).
      Leukocyte counts declined less in Ptx + MBG mice compared to Ptx-alone (p =
      0.024) or Ptx + G-CSF treatment (p = 0.031). Lymphocyte levels were higher after
      Ptx + MBG but not Ptx + G-CSF treatment compared to Ptx alone (p < 0.01). MBG
      increased CFU-GM activity in bone marrow and spleen (p < 0.001, p = 0.002) 2 days
      after Ptx. After two additional days (Ptx post-day 4), MBG restored
      granulocyte/monocyte ROS response to normal levels compared to Ptx-alone and
      increased ROS response compared to Ptx-alone or Ptx + G-CSF (p < 0.01, both). The
      studies indicate that oral MBG promoted maturation of HPC to become functionally
      active myeloid cells and enhanced peripheral blood leukocyte recovery after
      chemotoxic bone marrow injury.

PMID- 20140434
TI  - Unnecessary gastric decompression in distal elective bowel anastomoses in
      children: a randomized study.
AB  - BACKGROUND: The goal of this study was to investigate the role of nasogastric
      drainage in preventing postoperative complications in children with distal
      elective bowel anastomosis. Nasogastric drainage has been used as a routine
      measure after gastrointestinal surgery in children and adults to hasten bowel
      function, prevent postoperative complications, and shorten hospital stay.
      However, there has been no study that shows in a scientific manner the benefit of
      nasogastric drainage in children. METHODS: We performed a clinical, controlled,
      randomized trial comprising 60 children who underwent distal elective bowel
      anastomoses and compared postoperative complications between a group with
      nasogastric tube in place (n = 29) and one without it (n = 31). RESULTS:
      Demographic data and diagnoses were comparable in both groups (P = NS). No
      anastomotic leaks or enterocutaneous fistulae were found in any patient. There
      were no significant differences between the two groups with respect to abdominal
      distension, infection, or hospital stay. Only one patient in the experimental
      group required placement of the nasogastric tube due to persistent abdominal
      distension (3.2%). CONCLUSIONS: The routine use of nasogastric drainage after
      distal elective intestinal surgery in children can be eliminated. Its use should
      depend on the individual patient's situation.

PMID- 20140435
TI  - Exclusion of malignancy in thyroid nodules with indeterminate fine-needle
      aspiration cytology after negative 18F-fluorodeoxyglucose positron emission
      tomography: interim analysis.
AB  - BACKGROUND: In all, 20% of fine-needle aspiration (FNA) biopsies of thyroid
      nodules have an indeterminate diagnosis; of these, 80% are found to be benign
      after thyroidectomy. Some previous reports indicate that positron emission
      tomography (PET) with (18)F-fluorodeoxyglucose (FDG) imaging may predict
      malignancy status. We now report results on the first 51 patients in the largest
      prospective study of FDG-PET in patients with an indeterminate thyroid nodule
      FNA. METHODS: Eligible patients had a dominant thyroid nodule that was palpable
      or >or=1 cm in greatest dimension as seen by ultrasonography, and indeterminate
      histology of the FNA biopsy specimen. Participants underwent preoperative neck
      FDG-PET alone or FDG-PET with computed tomography (FDG-PET/CT). Images were
      evaluated qualitatively and semiquantitatively using the maximum standardized
      uptake value (SUV(max)). Final diagnosis was determined by histopathologic
      analysis after thyroidectomy. Descriptive statistical analysis was performed.
      RESULTS: A total of 51 patients underwent preoperative FDG-PET or FDG-PET/CT.
      Studies without focally increased uptake localized to the lesion were considered
      negative. For all lesions (10 malignant, 41 benign), the sensitivity,
      specificity, positive-predictive value (PPV), and negative-predictive value (NPV)
      were 80%, 61%, 33%, and 93%, respectively. Postoperatively, two malignant and six
      benign lesions were found to be <1 cm by pathology examination; one lesion was
      not measured. When these lesions were excluded, the sensitivity, specificity,
      PPV, and NPV were 100%, 59%, 36%, and 100%, respectively. CONCLUSIONS: Based on
      these preliminary data, FDG-PET may have a role in excluding malignancy in
      thyroid nodules with an indeterminate FNA biopsy. This finding justifies ongoing
      accrual to our target population of 125 participants.

PMID- 20140436
TI  - Occurrence of Vibrio parahaemolyticus and its specific phages from shrimp ponds
      in east coast of India.
AB  - Vibrio parahaemolyticus is a natural microflora of marine and coastal water
      bodies and associated with mortality of larval shrimp in penaeid shrimp in ponds.
      Bacteriophages occur virtually in all places where their hosts exist. In this
      study, total distribution of V. parahaemolyticus and its phages were examined in
      shrimp ponds, seawater, estuary, animal surface, and tissues. Total vibrio count
      in sediments of two ponds was found to be 2.6 * 10(3) and 5.6 * 10(3) cfu/g.
      Incidence of V. parahaemolyticus in the ponds was close, while it was markedly
      higher in the animal surface and tissue samples. Biochemically identified eight
      strains of V. parahaemolyticus (V1, V3-V6, V9, V11, and V12) were taken for
      further infection studies with bacteriophage. Totally five bacteriophages capable
      of infecting V. parahaemolyticus MTCC-451 strain were isolated from all the
      samples. One of the isolated bacteriophage Vp1 from estuary was able to lyse all
      the isolated V. parahaemolyticus strains we used. Therefore, the morphology of
      Vp1 was estimated in TEM. Vp1 phage head measuring approximately about 50-60 nm
      diameter with icosahedral outline and a contractile tails of diameter 7 nm and
      length 100 nm and it was identified as Myoviridae. Therefore, the phages have the
      potential application in destroying bacterial pathogens.

PMID- 20140437
TI  - The effect of tolterodine 4 and 8 mg on the heart rate variability in healthy
      subjects.
AB  - PURPOSE: To investigate the potential effect of tolterodine on the human heart
      rate variability (HRV). Oral antimuscarinic treatment for overactive bladder
      might significantly alter HRV, which is an important predictor for cardiac and
      all-cause mortality. Yet, little information exists regarding the influence of
      oral antimuscarinics on the HRV. METHODS: Healthy female volunteers were randomly
      assigned to either placebo, tolterodine extended release (ER) 4 or 8 mg. Before
      and 4 h post treatment, a 10 min electrocardiogram (ECG) was recorded in supine
      position. Frequency domain and time domain analysis of both ECG measurements
      resulted in very low frequency (VLF), low frequency (LF), and high frequency (HF)
      data, the root mean square of differences of successive NN (= normal to normal,
      i.e. interval between two R-peaks) intervals (RMSSD), and the standard deviation
      of the NN intervals (SDNN). RESULTS: Thirty subjects (mean age: 23.7 +/- 2.3
      years) were investigated. Placebo caused no significant HRV changes. Tolterodine
      4 mg significantly increased heart rate (HR) and significantly decreased VLF.
      Tolterodine 8 mg significantly decreased HF, VLF, RMSSD and SDNN and
      significantly increased HR and LF/HF ratio. The changes observed with 4 mg were
      not significantly different versus placebo, but 8 mg significantly increased
      LF/HF as compared to placebo. CONCLUSIONS: A single dose of 8 mg tolterodine ER,
      but not 4 mg seems to reduce resting HRV versus placebo in young healthy
      subjects. This might be particular relevant for patients with pre-existing
      cardiac conditions on daily overactive bladder drug treatment and should be
      further investigated in larger trials.

PMID- 20140438
TI  - Utility of NT-pro-BNP in patients undergoing transapical aortic valve
      replacement.
AB  - BACKGROUND: Transapical aortic valve replacement (TAVR) is increasingly being
      applied in conventionally inoperable patients with aortic stenosis. The utility
      of the cardiac marker NT-pro-BNP has yet not been assessed in this setting.
      METHODS: NT-pro-BNP was assessed preoperatively, postoperatively (day 1, 3, 5 and
      8) and 2 months after the intervention in 31 consecutive patients (13 men, 18
      women; median age 84) undergoing TAVR and the association with baseline
      characteristics and outcome was analysed. RESULTS: Baseline NT-pro-BNP was
      associated with baseline creatinine, left-ventricular mass index and NYHA class
      and predicted regression of LV-mass after 2 months. There was no correlation of
      NT-pro-BNP with measures of the aortic valve function before or after
      replacement. The increase of NT-pro-BNP 3 days after TAVR was inversely
      associated with a functional improvement of >or=1 NYHA class at 2 months.
      Baseline NT-pro-BNP was not associated with 2-month mortality and major adverse
      events (death/neurological deficit), whereas the postoperative increase of NT-pro
      BNP after TAVR showed a slightly significant inverse and the EuroSCORE a
      significant correlation. CONCLUSIONS: In multimorbid patients undergoing TAVR, NT
      pro-BNP independently predicted regression of LV-mass after 2 months and early
      decrease of NT-pro-BNP postoperatively indicated improvement of functional
      capacity at 2 months. There was no association of NT-pro-BNP with 2-month
      mortality.

PMID- 20140439
TI  - Sporadic four-repeat tauopathy with frontotemporal lobar degeneration,
      Parkinsonism, and motor neuron disease: a distinct clinicopathological and
      biochemical disease entity.
AB  - Tau is the pathological protein in several neurodegenerative disorders classified
      as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration
      (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in
      three Japanese patients presenting with Parkinsonism and motor neuron disease
      (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were
      examined). At autopsy, all cases showed FTLD with the most severe neuronal loss
      and gliosis evident in the premotor and precentral gyri. Although less severe,
      such changes were also observed in other brain regions, including the basal
      ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and
      degeneration of the corticospinal tract were evident. In addition, the affected
      regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary
      tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4
      repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic
      inclusions in the central nervous system; the astrocytic tau lesions were unique,
      and different in morphology from astrocytic plaques in CBD, or tufted astrocytes
      in PSP. However, immunoblotting of frozen brain samples available in two cases
      revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low
      molecular mass tau fragments characteristic of CBD and PSP, respectively. No
      mutations were found in the tau gene in either of the two cases. Based on these
      clinicopathological, biochemical, and genetic findings, we consider that the
      present three patients form a distinct 4R tauopathy associated with sporadic
      FTLD.

PMID- 20140440
TI  - Phosphaturic mesenchymal tumor of spinal nerve in a patient with osteomalacia and
      multiple fractures.

PMID- 20140441
TI  - Critical appraisal of case-control studies of risk factors or etiology of
      Hyperemesis gravidarum.
AB  - OBJECTIVE: Critical appraisal of published case-control studies examining the
      etiology or risk factors of Hyperemesis gravidarum (HG). MATERIALS AND METHODS:
      We searched the Medline/PubMed database from 1966 to February 12, 2009. A total
      of 48 case-control studies were retrieved and each article was evaluated using a
      structured assessment devised for the purpose. RESULTS: The case-control studies
      were published between 1978 and 2008. The majority investigated hormonal,
      gastrointestinal, and metabolic risk factors associated with hyperemesis
      gravidarum (37 studies). Selection bias and non-response received insufficient
      attention in many articles. Sample size varied widely with a median number of 40
      cases and 42 controls. Association uncommonly was expressed by odds ratios and
      confidence intervals (9 studies), confounding rarely controlled for (10 studies)
      and few examined effect modification (2 studies). CONCLUSION: We are concerned as
      far the inadequacies in the design, analysis, and reporting of case-control
      studies examining the etiology of HG. It is mandatory to follow adequate clinical
      research methodology in executing and reporting such studies.

PMID- 20140442
TI  - The mtDNA composition of Uzbekistan: a microcosm of Central Asian patterns.
AB  - In order to better characterize and understand the mtDNA population genetics of
      Central Asia, the mtDNA control regions of over 1,500 individuals from Uzbekistan
      have been sequenced. Although all samples were obtained from individuals residing
      in Uzbekistan, individuals with direct ancestry from neighboring Central Asian
      countries are included. Individuals of Uzbek ancestry represent five distinct
      geographic regions of Uzbekistan: Fergana, Karakalpakstan, Khorezm, Qashkadarya,
      and Tashkent. Individuals with direct ancestry in nearby countries originate from
      Kazakhstan, Kyrgyzstan, Russia, Afghanistan, Turkmenistan, and Tajikistan. Our
      data reinforce the evidence of distinct clinal patterns that have been described
      among Central Asian populations with classical, mtDNA, and Y-chromosomal markers.
      Our data also reveal hallmarks of recent demographic events. Despite their
      current close geographic proximity, the populations with ancestry in neighboring
      countries show little sign of admixture and retain the primary mtDNA patterns of
      their source populations. The genetic distances and haplogroup distributions
      among the ethnic populations are more indicative of a broad east-west cline among
      their source populations than of their relatively small geographic distances from
      one another in Uzbekistan. Given the significant mtDNA heterogeneity detected,
      our results emphasize the need for heightened caution in the forensic
      interpretation of mtDNA data in regions as historically rich and genetically
      diverse as Central Asia.

PMID- 20140443
TI  - Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449
      outpatients with Parkinson's disease.
AB  - Neuropsychiatric symptoms (NPS) of Parkinson's disease (PD) are of growing
      diagnostic and therapeutic importance. Data on their prevalence and
      characteristics have been primarily derived from highly selective clinical
      populations. We have conducted a national study in the outpatient care sector to
      provide a fuller characterization of the frequency of dementia, depression, and
      other NPS in PD outpatients. We also examined associations with biosocial and
      neurological variables. A nationwide representative sample of 1,449 PD
      outpatients was examined with a standardized clinical interview. PD severity was
      rated with the Hoehn and Yahr (HY) scale and the Unified Parkinson's Disease
      Rating Scale. Depression was measured with the Montgomery-Asberg Depression
      Rating Scale. Cognitive impairment and dementia were assessed with the Mini
      Mental State Exam and according to diagnostic criteria. Logistic regression
      analyses were used to investigate associations. At least one NPS occurred in 71%
      of all patients with PD. The estimated prevalences (ranges) by age group and HY
      stage were: depression, 25% (13.2-47.9%), dementia, 29% (12.2-59.4%), and
      psychotic syndromes, 12.7% (3.1-40.9%). Other frequent complications were sleep
      disturbances (49%) and anxiety (20%). Depression was associated with gender but
      not with age. Dementia was associated with age. The rates and comorbidity of
      depression and dementia were driven by PD severity. NPS were highly prevalent in
      our comprehensive patient sample, largely representative of management problems
      occurring in an outpatient setting. PD outpatients are at an increased risk for
      all neuropsychiatric conditions, increasing with PD severity but not with age or
      age of onset (except dementia), revealing challenging symptom patterns.

PMID- 20140444
TI  - Early development of spasticity following stroke: a prospective, observational
      trial.
AB  - This study followed a cohort of 103 patients at median 6 days, 6 and 16 weeks
      after stroke and recorded muscle tone, pain, paresis, Barthel Index and quality
      of life score (EQ-5D) to identify risk-factors for development of spasticity.
      24.5% of stroke victims developed an increase of muscle tone within 2 weeks after
      stroke. Patients with spasticity had significantly higher incidences of pain and
      nursing home placement and lower Barthel and EQ-5D scores than patients with
      normal muscle tone. Early predictive factors for presence of severe spasticity
      [modified Ashworth scale score (MAS) >or=3] at final follow-up were moderate
      increase in muscle tone at baseline and/or first follow-up (MAS = 2), low Barthel
      Index at baseline, hemispasticity, involvement of more than two joints at first
      follow-up, and paresis at any assessment point. The study helps to identify
      patients at highest risk for permanent and severe spasticity, and advocates for
      early treatment in this group.

PMID- 20140445
TI  - Remote cerebral hematomas in patients treated with intravenous rt-PA.
AB  - The frequency, clinical presentation, radiological features, and prognosis of
      remote cerebral hematomas (rPH) are not well known. We report our experience in
      patients treated with intravenous rt-PA. We reviewed our database of consecutive
      patients treated at our hospital from 1999 to 2008. We used the
      inclusion/exclusion criteria of the ECASS-2 study from 1999 to 2003, and the
      criteria of the SITS-MOST study since 2004. A follow-up CT scan was obtained in
      all of the patients within the first 36 h of treatment. Cerebral hemorrhagic
      complications were classified as hemorrhagic infarction (HI-1/HI-2) and
      parenchymal hematoma (PH-1/PH-2). The rPH was defined as any extra-ischemic
      hemorrhagic lesion observed in the follow-up CT. A favorable outcome was defined
      as a score 0-1 on the Rankin scale at 3 months. We treated 210 patients (mean age
      67.6 +/- 12.4 years, 56% were men). The median initial NIHSS score was 14.
      Patients with rPH (n = 7) had a mean age of 72.4 +/- 7.5 years and 43% were men.
      The median initial NIHSS score was 15. Three patients had multifocal rPH; three
      patients had a single rPH and in one patient the rPH was associated with a PH-2.
      rPH were lobar in six patients and in brainstem in one patient, symptomatic in
      five patients and asymptomatic in two patients. The outcome was unfavorable in
      all of them; four deaths (57%) were recorded. Remote cerebral hemorrhage is an
      infrequent complication after rt-PA treatment (3.3%), it is usually lobar and
      symptomatic and has an uniformly unfavorable outcome.

PMID- 20140446
TI  - Spontaneous regression of a midbrain lesion in a patient with chronic
      transtentorial herniation: is it a pre-syrinx?

PMID- 20140447
TI  - The effects of two nights of sleep deprivation with or without energy restriction
      on immune indices at rest and in response to cold exposure.
AB  - The purpose of the study was to determine the effects of two nights of sleep
      deprivation with or without energy restriction on immune indices at rest and in
      response to cold exposure. On three randomised occasions ten males slept normally
      [mean (SD): 436 (21) min night(-1); CON], were totally sleep-deprived (SDEP), or
      were totally sleep-deprived and 90% energy-restricted (SDEP + ER) for 53 h. After
      53 h (1200 h) participants performed a seated cold air test (CAT) at 0.0 degrees
      C until T (re) decreased to 36.0 degrees C. Circulating leucocyte counts,
      neutrophil degranulation, stress hormones and saliva secretory IgA (S-IgA) were
      determined at 0 h, 24 h, 48 h, pre-CAT, post-CAT, 1-h and 2-h post-CAT. One night
      on SDEP increased bacterially stimulated neutrophil degranulation (21%, P <
      0.05), and two nights on SDEP and SDEP + ER increased S-IgA concentration (40 and
      44%; P < 0.01). No other significant effects were observed for immuno-endocrine
      measures prior to CAT. CAT duration was not different between trials [mean (SD):
      133 (53) min] and T (re) decreased to 35.9 (0.3) degrees C. Modest whole-body
      cooling decreased circulating lymphocyte counts (25%; P < 0.01), S-IgA
      concentration (36%; P < 0.01) and secretion rate (24%; P < 0.05). A neutrophilia
      occurred post-CAT on CON and SDEP and 2-h post-CAT on SDEP + ER (P < 0.01).
      Modest whole-body cooling also decreased neutrophil degranulation on CON (22%)
      and SDEP (18%; P < 0.05). Plasma cortisol and norepinephrine increased post-CAT
      (31 and 346%, P < 0.05), but modest whole-body cooling did not alter plasma
      epinephrine. In conclusion, two nights of SDEP or SDEP + ER did not compromise
      resting immune indices. However, modest whole-body cooling (T(re) 35.9 degrees C)
      decreased circulating lymphocytes, neutrophil degranulation and S-IgA, but
      responses were not amplified by prior SDEP or SDEP + ER.

PMID- 20140448
TI  - Effects of acupuncture and heating on blood volume and oxygen saturation of human
      Achilles tendon in vivo.
AB  - The purpose of this study was to investigate the effects of acupuncture (dry
      needling) and heating (application of hot pack) treatments on the blood volume
      and oxygen saturation of the human Achilles tendon in vivo. Nine healthy males
      participated in this study. During the treatments (acupuncture and heating; both
      10 min) and recovery period (30 min), the blood volume and oxygen saturation of
      the Achilles tendon were measured using red laser lights. During needle
      insertion, the blood volume and oxygen saturation of the tendon increased
      significantly from the pre-treatment level and these values remained high
      throughout the 30-min recovery period. During heating treatment, the blood volume
      and oxygen saturation of the tendon also increased significantly. Although the
      increased blood volume was not maintained after removal of the hot pack, the
      oxygen saturation remained significantly elevated throughout the 30-min recovery
      period. These results suggested that acupuncture and heating treatments enhanced
      the blood flow in the tendon. The long-lasting increase, especially with
      acupuncture treatment, in the blood supply to the tendon implies that these
      treatments may have therapeutic effects on injured tendons.

PMID- 20140449
TI  - Hydrogen peroxide as an endothelium-derived hyperpolarizing factor.
AB  - The endothelium plays an important role in maintaining cardiovascular homeostasis
      by synthesizing and releasing several vasodilating substances, including
      vasodilator prostaglandins, nitric oxide (NO), and endothelium-derived
      hyperpolarizing factor (EDHF). Since the first report on the existence of EDHF,
      several substances/mechanisms have been proposed for the nature of EDHF,
      including epoxyeicosatrienoic acids (metabolites of arachidonic P450 epoxygenase
      pathway), K ions, and electrical communications through myoendothelial gap
      junctions. We have demonstrated that endothelium-derived hydrogen peroxide
      (H(2)O(2)) is an EDHF in animals and humans. For the synthesis of H(2)O(2)/EDHF,
      endothelial NO synthase system that is functionally coupled with Cu,Zn-superoxide
      dismutase plays a crucial role. Importantly, endothelium-derived H(2)O(2) plays
      important protective roles in the coronary circulation, including coronary
      autoregulation, protection against myocardial ischemia/reperfusion injury, and
      metabolic coronary vasodilatation. Indeed, our H(2)O(2)/EDHF theory demonstrates
      that endothelium-derived H(2)O(2), another reactive oxygen species in addition to
      NO, plays important roles as a redox-signaling molecule to cause vasodilatation
      as well as cardioprotection. In this review, we summarize our current knowledge
      on H(2)O(2)/EDHF regarding its identification and mechanisms of synthesis and
      actions.

PMID- 20140450
TI  - Genetically modified mice-successes and failures of a widely used technology.
AB  - Genetically modified mice, created by random integration of a transgene into the
      genome or by targeted mutation of a specific gene, have proven to be extremely
      powerful tools for studying gene function in vivo. In this article, we give (1) a
      short overview of the traditional methods in mouse transgenesis and (2) a
      discussion of the problems with these methods, (3) more recent methods that were
      developed to overcome these problems, and (4) an outlook on future directions in
      gene targeting.

PMID- 20140451
TI  - Trypanocidal activity and acute toxicity assessment of triterpene acids.
AB  - The present study evaluates the in vitro and in vivo trypanocidal activity of
      ursolic acid and oleanolic acid against the Bolivia strain of Trypanosoma cruzi.
      Their acute toxicity is also assessed on the basis of median lethal dose (DL50)
      determination and quantification of biochemical parameters. Ursolic acid is the
      most active compound in vitro, furnishing IC50 of 25.5 microM and displaying 77%
      of trypomastigote lysis at a concentration of 128 microM. In agreement with in
      vitro assays, the results obtained for the in vivo assay reveals that ursolic
      acid (at a dose of 20 mg/Kg/day) provides the most significant reduction in the
      number of parasites at the parasitemic peak. Results concerning the LD50 assay
      and the biochemical parameters evaluated in the present study demonstrate that
      these substances can be safely used on an experimental basis.

PMID- 20140452
TI  - Ticks (Acari: Ixodidae) infesting wild birds in the eastern Amazon, northern
      Brazil, with notes on rickettsial infection in ticks.
AB  - The aim of the study was to report tick infestations on wild birds in a region of
      the eastern Brazilian Amazon and evaluate the rickettsial infection of these
      ticks. Wild birds captured by mist nets were examined for the presence of ticks,
      which were collected and identified to species by morphology or molecular
      methods. In addition, part of these ticks was individually tested by polymerase
      chain reaction targeting portions of the rickettsial genes gltA and ompA. Among
      331 captured birds, representing 56 species, 133 individuals (40.2%) from 34
      species were found infested by 443 ticks, being Amblyomma longirostre (Koch) the
      most common (103 larvae, 12 nymphs), followed by Amblyomma humerale Koch (15
      larvae, 3 nymphs), Amblyomma geayi Neumann (seven larvae, one nymph), Amblyomma
      calcaratum Neumann (one larva, four nymphs), Amblyomma coelebs Neumann (two
      larvae), and Haemaphysalis juxtakochi Cooley (one larva, two nymphs). Other 285
      larvae and 7 nymphs collected from birds could not be identified to species and
      were morphologically identified as Amblyomma spp. The species A. humerale and A.
      geayi are recorded for first time parasitizing birds in the Neotropical region.
      Among 67 A. longirostre and 7 A. geayi, 38 (56.7%) and 4 (57.1%), respectively,
      were found infected by Rickettsia amblyommii. In spite of R. amblyommii being not
      currently recognized as human or animal pathogen, there has been serological
      evidence for human and canine infection by this agent in the USA and in the
      Brazilian western Amazon.

PMID- 20140453
TI  - Monitoring of failure of chloroquine treatment for Plasmodium vivax using
      polymerase chain reaction in Sanliurfa province, Turkey.
AB  - Malaria is a complex disease that varies widely in epidemiology and clinical
      manifestation in the southeastern part of Turkey. In many regions of the world,
      chloroquine (CQ) has been the standard treatment for Plasmodium vivax. However,
      the resistance of the Plasmodium species to antimalarial drugs has become an
      increasing problem and a concern worldwide. Our target was to determine the
      Plasmodium species in the southeast region of Turkey and the therapeutic efficacy
      of CQ used in the treatment of malaria. Blood samples were collected from 180
      patients infected with malaria before and after CQ treatment and were subjected
      to DNA isolation. The isolated DNA was amplified by a seminested multiplex
      polymerase chain reaction (SnM-PCR) including primers selected on Plasmodium
      small subunit ribosomal RNA (ssrRNA) genes for identification of the malaria
      species. The SnM-PCR results showed that only P. vivax exists in this province.
      It was also determined that there is a therapeutic failure to CQ in 9.5% of
      patients. These were the second report on identification of P. vivax and the
      third report on determination of the therapeutic failure in patients who used CQ
      to cure human malaria in the southeastern region of Turkey. Our results
      demonstrate that the SnM-PCR is a sensitive, specific, and a rapid tool for the
      differentiation of malaria species.

PMID- 20140454
TI  - The foundation of extranuclear inheritance: plastid and mitochondrial genetics.
AB  - In 1909 two papers by Correns and by Baur published in volume 1 of Zeitschrift
      fur induktive Abstammungs- und Vererbungslehre (now Molecular Genetics and
      Genomics) reported on the non-Mendelian inheritance of chlorophyll deficiencies.
      These papers, reporting the very first cases of extranuclear inheritance, laid
      the foundation for a new field: non-Mendelian or extranuclear genetics. Correns
      observed a purely maternal inheritance (in Mirabilis), whereas Baur found a
      biparental inheritance (in Pelargonium). Correns suspected the non-Mendelian
      factors in the cytoplasm, while Baur believed that the plastids carry these
      extranuclear factors. In the following years, Baur's hypothesis was proved to be
      correct. Baur subsequently developed the theory of plastid inheritance. In many
      genera the plastids are transmitted only uniparentally by the mother, while in a
      few genera there is a biparental plastid inheritance. Commonly there is random
      sorting of plastids during ontogenetic development. Renner and Schwemmle as well
      as geneticists in other countries added additional details to this theory.
      Pioneering studies on mitochondrial inheritance in yeast started in 1949 in the
      group of Ephrussi and Slonimski; respiration-deficient cells (petites in yeast,
      poky in Neurospora) were demonstrated to be due to mitochondrial mutations.
      Electron microscopical and biochemical studies (1962-1964) showed that plastids
      and mitochondria contain organelle-specific DNA molecules. These findings laid
      the molecular basis for the two branches of extranuclear inheritance: plastid and
      mitochondrial genetics.

PMID- 20140455
TI  - Gain of deleterious function causes an autoimmune response and Bateson-Dobzhansky
      Muller incompatibility in rice.
AB  - Reproductive isolation plays an important role in speciation as it restricts gene
      flow and accelerates genetic divergence between formerly interbreeding
      population. In rice, hybrid breakdown is a common reproductive isolation observed
      in both intra and inter-specific crosses. It is a type of post-zygotic
      reproductive isolation in which sterility and weakness are manifested in the F(2)
      and later generations. In this study, the physiological and molecular basis of
      hybrid breakdown caused by two recessive genes, hbd2 and hbd3, in a cross between
      japonica variety, Koshihikari, and indica variety, Habataki, were investigated.
      Fine mapping of hbd2 resulted in the identification of the causal gene as casein
      kinase I (CKI1). Further analysis revealed that hbd2-CKI1 allele gains its
      deleterious function that causes the weakness phenotype by a change of one amino
      acid. As for the other gene, hbd3 was mapped to the NBS-LRR gene cluster region.
      It is the most common class of R-gene that triggers the immune signal in response
      to pathogen attack. Expression analysis of pathogen response marker genes
      suggested that weakness phenotype in this hybrid breakdown can be attributed to
      an autoimmune response. So far, this is the first evidence linking autoimmune
      response to post-zygotic isolation in rice. This finding provides a new insight
      in understanding the molecular and evolutionary mechanisms establishing post
      zygotic isolation in plants.

PMID- 20140456
TI  - The classical pathway of melanogenesis is not essential for melanin synthesis in
      the adult retinal pigment epithelium.
AB  - Premelanosomes are presumed to be essential for melanogenesis in melanocytes and
      pre-natal retinal pigment epithelium (RPE) cells. We analysed melanin synthesis
      in adenoviral-transduced tyrosinase-gene-expressing amelanotic RPE (ARPE) 19
      cells to determine whether premelanosome formation is needed for post-natal
      melanogenesis. The synthesis of melanogenic proteins and melanin granules was
      investigated by immunocytochemistry and light and electron microscopy. The
      occurrence of tyrosinase was analysed ultrastructurally by dihydroxyphenylalanine
      histochemistry. The viability of transduced cell cultures was examined via MTT
      assay. We found active tyrosinase in small granule-like vesicles throughout the
      cytoplasm and in the endoplasmic reticulum and nuclear membrane. Tyrosinase was
      also associated with multi-vesicular and multi-lamellar organelles. Typical
      premelanosomes, structural protein PMEL17, tyrosinase-related protein 1 and
      classic melanosomal stages I-IV were not detected. Instead, melanogenesis took
      place inside multi-vesicular and multi-lamellar bodies of unknown origin.
      Viability was not affected up to 10 days after transduction. We thus demonstrate
      a pathway of melanin formation lacking typical hallmarks of melanogenesis.

PMID- 20140457
TI  - Muscle and neuronal differentiation in primary cell culture of larval Mytilus
      trossulus (Mollusca: Bivalvia).
AB  - Molluscan in vitro technology allows the study of the differentiation of isolated
      cells undergoing experimental manipulations. We have used the immunofluorescence
      technique and laser scanning microscopy to investigate the organization of muscle
      proteins (actin, myosin, paramyosin, and twitchin) and the localization of
      neurotransmitters (serotonin and FMRFamide) in cultured mussel larval cells.
      Differentiation into muscle and neuron-like cells occurs during the cultivation
      of mussel cells from premyogenic and prenervous larval stages. Muscle proteins
      are colocalized in contractile cells through all stages of cultivation. The
      cultivation of mussel cells on various substrates and the application of integrin
      receptor blockers suggest that an integrin-dependent mechanism is involved in
      cell adhesion and differentiation. Dissociated mussel cells aggregate and become
      self-organized in culture. After 20 days of cultivation, they form colonies in
      which serotonin- and FMRFamide-immunoreactive cells are located centrally,
      whereas muscle cells form a contractile network at the periphery. The pattern of
      thick and thin filaments in cultivated mussel cells changes according to the
      scenario of muscle arrangement in vivo: initially, a striated pattern of muscle
      filaments forms but is then replaced by a smooth muscle pattern with a diffuse
      distribution of muscle proteins, typical of muscles of adult molluscs. Myogenesis
      in molluscs thus seems to be a highly dynamic and potentially variable process.
      Such a "flexible" developmental program can be regarded as a prerequisite for the
      evolution of the wide variety of striated and smooth muscles in larval and adult
      molluscs.

PMID- 20140458
TI  - Hyperpolarization-activated and cyclic nucleotide-gated channels are
      differentially expressed in juxtaglomerular cells in the olfactory bulb of mice.
AB  - In the olfactory bulb, input from olfactory receptor neurons is processed by
      neuronal networks before it is relayed to higher brain regions. In many neurons,
      hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels generate
      and control oscillations of the membrane potential. Oscillations also appear
      crucial for information processing in the olfactory bulb. Four channel isoforms
      exist (HCN1-HCN4) that can form homo- or heteromers. Here, we describe the
      expression pattern of HCN isoforms in the olfactory bulb of mice by using a novel
      and comprehensive set of antibodies against all four isoforms. HCN isoforms are
      abundantly expressed in the olfactory bulb. HCN channels can be detected in most
      cell populations identified by commonly used marker antibodies. The combination
      of staining with marker and HCN antibodies has revealed at least 17 different
      staining patterns in juxtaglomerular cells. Furthermore, HCN isoforms give rise
      to an unexpected wealth of co-expression patterns but are rarely expressed in the
      same combination and at the same level in two given cell populations. Therefore,
      heteromeric HCN channels may exist in several cell populations in vivo. Our
      results suggest that HCN channels play an important role in olfactory information
      processing. The staining patterns are consistent with the possibility that both
      homomeric and heteromeric HCN channels are involved in oscillations of the
      membrane potential of juxtaglomerular cells.

PMID- 20140460
TI  - Cryptogenic organizing pneumonia after rituximab therapy for presumed post-kidney
      transplant lymphoproliferative disease.
AB  - Cryptogenic organizing pneumonia (COP, formerly bronchiolitis obliterans
      organizing pneumonia) is rare in children. We describe an 11-year-old girl with
      Epstein-Barr virus (EBV) reactivation/presumed post-transplant
      lymphoproliferative disease (PTLD) 15 months after undergoing a deceased donor
      kidney transplantation. Treatment with reduced immunosuppression, ganciclovir,
      and cytomegalovirus immunoglobulin was complicated by severe graft rejection,
      prompting therapy with methylprednisolone, anti-thymocyte globulin and four
      weekly doses of rituximab (total 1500 mg/m(2)). Tacrolimus- and prednisone-based
      anti-rejection prophylaxis was complemented with low-dose sirolimus. When the
      lactate dehydrogenase and uric acid levels rose 10 weeks after the first
      rituximab infusion and bilateral pulmonary nodules were detected by computerized
      tomography, recurrence of PTLD was suspected. Open lung biopsy of the clinically
      asymptomatic patient identified the nodules as COP, characterized by abundant
      CD3(+) T-cells, few B-cells, and the absence of EBV, cytomegalovirus, or
      adenovirus antigens. With normalization of the peripheral B-cell count, EB
      viremia reappeared and persisted, despite minimal immunosuppression. Four years
      later, the patient was diagnosed with classical Hodgkin lymphoma-type PTLD with
      multiple pulmonary and abdominal nodes. This first report of rituximab
      associated, pediatric COP highlights the risk of pulmonary complications after
      treatment with B-cell depleting agents in solid organ transplant recipients, and
      the importance of a histopathologic diagnosis and vigilant follow-up of such
      lesions.

PMID- 20140461
TI  - General anesthesia in a patient with Parkes Weber syndrome with high-output
      cardiac failure due to multiple arteriovenous fistulas complicated by severe
      aortic regurgitation.
AB  - Parkes Weber syndrome is a rare disease characterized by overgrowth of an
      extremity linked to the presence of an arteriovenous malformation with multiple
      arteriovenous fistulas (AVFs). We report a patient with Parkes Weber syndrome
      with high-output cardiac failure due to multiple AVFs complicated by severe
      aortic regurgitation (AR) who required surgical treatment for AVFs. Division of
      the left deep femoral artery and banding of the left superficial femoral artery
      were performed. Such procedures can cause aggravation of AR and left ventricular
      failure due to the sudden increase in cardiac afterload. Pulmonary artery
      pressure, mixed venous oxygen saturation and cardiac index monitored by a
      thermodilution catheter, and a transesophageal echocardiography were useful in
      evaluating the effect of the surgical procedure and resultant acute increase in
      cardiac afterload on cardiac output and left ventricular function.

PMID- 20140462
TI  - Effects of landiolol on left ventricular function during electroconvulsive
      therapy: a transthoracic echocardiographic study.
AB  - The purpose of this study was to examine the effects of landiolol on left
      ventricular (LV) systolic function, using transthoracic echocardiography, during
      electroconvulsive therapy (ECT). Fourteen patients undergoing ECT were studied.
      Bilateral ECT was performed after administration of thiopentone (2 mg/kg),
      succinylcholine (1 mg/kg), and initiation of assisted mask ventilation with 100%
      oxygen. Patients received a bolus injection of landiolol (0.125 mg/kg) or saline
      immediately after anesthetic induction and prior to electrical shock. LV systolic
      function was examined by transthoracic echocardiography prior to anesthetic
      induction, throughout the ECT procedure, and for 10 min after the seizure.
      Electrical shock resulted in a significant decrease in fractional area change
      (FAC) when compared with the awake condition in the control group [FAC when
      awake: 48 +/- 3%; 1 min after ECT: 38 +/- 4%*; 2 min after ECT: 36 +/- 4%*; 3 min
      after ECT: 40 +/- 3%*; mean +/- standard deviation, *p < 0.05 compared with
      awake]. Landiolol infusion stabilized systemic hemodynamics and LV systolic
      function. The study demonstrated that landiolol is a suitable agent to minimize
      hemodynamic changes and transthoracic echocardiographic variability after ECT.

PMID- 20140463
TI  - Minimal invasive anterior lumbar interbody fusion (mini ALIF).

PMID- 20140464
TI  - Rotational hypermobility of disc wedging using kinematic CT: preliminary study to
      investigate the instability of discs in degenerated scoliosis in the lumbar
      spine.
AB  - The number of patients showing lumbar degenerative scoliosis, including disc
      wedging, has increased, and examination of the mechanism of spinal nerve
      compression due to lateral and rotational mobility of the lumbar spine is
      necessary. Thirty-two patients with L4-L5 disc wedging but without antero- or
      retrospondylolisthesis and ten age-matched controls were examined. The angle of
      disc wedging and change in the angle between left and right bending were
      evaluated by anterior-posterior X-ray images of patients while they were in a
      standing position. The degree of disc degeneration and existence of vacuum
      phenomena were evaluated at the L4-L5 discs. Rotational mobility between maximal
      right and left rotation was examined by computed tomography (CT). Rotational
      mobility was measured using the spinal transverse processes of L4 and L5. The
      relationship between these factors was statistically evaluated using multivariate
      analysis and Spearman's correlation test. There was a significant increase in the
      average rotational mobility of the L4-L5 disc-wedging group. In the L4-L5 disc
      wedging group, the increased angle of disc wedging and change in the angle
      between left and right bending correlated with increased rotational mobility. The
      degree of disc degeneration did not affect rotational mobility. However,
      existence of vacuum phenomena increased the rotational mobility of the L4-L5 disc
      wedging group. This is the first study to evaluate the rotational hypermobility
      of L4-L5 disc wedging in patients without antero- or retrospondylolisthesis using
      kinematic CT. Increases in the wedging angle and abnormal instability of lateral
      bending correlated with increased rotational mobility. For surgical planning of
      degenerative L4-L5 disc wedging, it is important to consider rotational
      hypermobility using kinematic CT or X-ray imaging findings of lateral bending.

PMID- 20140465
TI  - Accuracy and complications of transpedicular C2 screw placement without the use
      of spinal navigation.
AB  - The objective of the study was to describe the technique, accuracy of placement
      and complications of transpedicular C2 screw fixation without spinal navigation.
      Patients treated by C2 pedicle screw fixations were identified from the surgical
      log book of the department. Clinical data were extracted retrospectively from the
      patients' charts. Pedicle screw placement accuracy was assessed on postoperative
      CT scans according to Gertzbein and Robbins (GRGr). A total of 27 patients were
      included in the study. The mean age of the patients was 56 +/- 22.0 years; 51.9%
      of them were female. As much as 17 patients suffered from trauma, 5 of
      degenerative disease, 3 of inflammations and 2 of metastatic disease. A total of
      47 C2 transpedicular screw fixations were performed. The canulated screws were
      inserted under visual control following the preparation of the superior surface
      of the isthmus and of the medial surface of the pedicles of the C2.
      Intraoperative fluoroscopy was additionally used. The postoperative CT findings
      showed in 55.3% GRGr 1, in 27.7% GRGr 2, in 10.6% GRGr 3, and in 6.3% GRGr 4
      pedicle screw insertion accuracy. Screw insertions GRGr 5 were not observed.
      Screw malpositioning (i.e., GRGr 3 and 4) was significantly associated with thin
      (<5 mm) pedicle diameters and with surgery for C2 fractures. In the three
      patients with screw insertions GRGr 4, postoperative angiographies were performed
      to exclude vertebral artery affections. In one of these three cases, the screw
      caused a clinically asymptomatic vertebral artery compression. Hardware failures
      did not occur. In one patient, postoperative pneumonia resulted in the death of
      the patient. Careful patient selection and surgical technique is necessary to
      avoid vertebral artery injury in C2 pedicle screw fixation without spinal
      navigation. A slight opening of the vertebral artery canal (Gertzbein and Robbins
      grade < or =3) does not seem to put the artery at risk. However, the high rate of
      misplaced screws when inserted without spinal navigation, despite the fact that
      no neurovascular injury occurred, supports the use of spinal navigation in C2
      pedicle screw insertions.

PMID- 20140466
TI  - Ranunculus glacialis L.: successful reproduction at the altitudinal limits of
      higher plant life.
AB  - Biodiversity decreases with increasing altitude, mainly because of the
      increasingly adverse climate. In the European Alps, only a few plant species
      occur above 4,000 m a.s.l., among these is Ranunculus glacialis L. Current
      studies have shown that R. glacialis has a highly conservative growth strategy
      and low developmental plasticity in response to different dates of snowmelt.
      Therefore, it was of particular interest to observe whether this strategy is
      maintained at higher altitudes and to reveal the reproductive limits. We examined
      the effect of the date of snowmelt on reproductive development and reproductive
      success in R. glacialis over several years at two subnival sites (2,650 and 2,880
      m a.s.l.) and at a nival site (3,440 m a.s.l.) in the Austrian Alps. At the
      subnival sites, reproductive performance was relatively stable (prefloration
      period, i.e. snowmelt to onset of anthesis, 2-3 weeks; postfloration period, i.e.
      onset of anthesis until fruit maturity, 4-5 weeks). Depending on the date of
      flowering, the mean seed/ovule (S/O) ratio was 0.5-0.8. The temporal safety
      margin between seed maturation and the onset of winter conditions was at least 1
      month. The situation was quite different in the nival zone: the prefloration
      period usually lasted 1 month, anthesis up to 2 weeks, and seed development 6-7
      weeks; when seeds matured in time, the S/O ratio was 0.4-0.6. Overall, R.
      glacialis shows a high developmental plasticity. At higher altitudes, R.
      glacialis can double the time taken for seed development but runs a high risk of
      seeds not maturing in time.

PMID- 20140467
TI  - A comparative light and electron microscopic analysis of microspore and tapetum
      development in fertile and cytoplasmic male sterile radish.
AB  - To gain further insight into the abortive stages and ultrastructural changes
      leading to pollen degeneration of a novel cytoplasmic male sterile radish 805A,
      we compared differences of cellular and subcellular structure of sterile anther
      with fertile anther by light and electron microscopy analysis. Two types of
      locule degeneration in sterile anther were detected, of which the time of
      degeneration occurred and completed was different. In type I, abnormality of
      pollen mother cells (PMCs) and tapetal cells, including condensation of cytoplasm
      and large vacuoles within tapetal cells, was shown at PMC stage. In type II,
      meiosis and early tetrad stage progressed normally except for large vacuoles that
      appeared in tapetal cells. Ultrastructural alterations of the cellular
      organization were observed in the type II locules, such as chromatin condensation
      at the periphery of the nucleus and degeneration of the karyotheca, compared with
      normal pollen development. The results suggested that the cytoplasmic male
      sterility anther degeneration was probably caused by dysfunctions of tapetum and
      vacuolation of tapetum, PMCs, and microspores. Thus, the identical factors, which
      induced CMS in the same cytoplasmic and nuclear genetic background, might affect
      development of tapetum and microspore at different stages during the cytoplasmic
      male sterile 805A anther development.

PMID- 20140468
TI  - Identification of genes regulated by ammonium availability in the roots of
      maritime pine trees.
AB  - Conifers have a preference for ammonium over nitrate as the main inorganic
      nitrogen source. However, it is unknown how changes in nitrogen nutrition may
      affect transcription profiles. In this study, microarray analysis and suppressive
      subtraction hybridization were used to identify differentially expressed genes in
      the roots of maritime pine exposed to changes in ammonium availability. A total
      of 225 unigenes that were differentially regulated by changes in ammonium
      nutrition were identified. Most of the unigenes were classified into seven
      functional categories by comparison with sequences deposited in the databases. A
      significant proportion of these genes were encoded for ammonium-regulated
      proteins of unknown functions. The differential expression of selected candidate
      genes was further validated in plants subjected to ammonium excess/deficiency.
      The transcript levels of representative genes were compared in maritime pine
      roots, 1, 15 and 35 days after nutritional treatments. Gene expression patterns
      suggest the existence of potential links between ammonium-responsive genes and
      genes involved in amino acid metabolism, particularly in asparagine biosynthesis
      and utilization. Functional analyses and exploration of the natural variability
      in maritime pine populations for a number of relevant genes are underway.

PMID- 20140469
TI  - Current understanding of the factors regulating methionine content in vegetative
      tissues of higher plants.
AB  - Methionine is a nutritionally essential, sulfur-containing amino acid found in
      low levels in plants, which often limits its value as a source of dietary protein
      to humans and animals. Methionine is also a fundamental metabolite in plant cells
      since, through its first metabolite, S-adenosylmethionine (SAM), it controls the
      level of several key metabolites, such as ethylene, polyamines and biotin. SAM is
      also the primary methyl group donor that regulates different processes in plants.
      Despite its nutritional and regulatory significance, the factors regulating
      methionine content in plants are not fully known. In this review, we summarize
      the current knowledge and recent progress made in our understanding of the
      methionine metabolism. The enzymes and substrates that regulate methionine
      synthesis were described, as well as the influences of the catabolic pathways of
      methionine on its content. The current effort to tailor an improvement of
      methionine content in vegetative tissues with minimal interference in plant
      growth and productivity is described as well. The accumulated knowledge has
      provided new insights into the control of methionine level in plants and, in some
      cases, has resulted in significant improvements in the nutritional value of
      plants.

PMID- 20140470
TI  - Ten-year survival of ART restorations in permanent posterior teeth.
AB  - This study evaluated the 10-year clinical performance of high-viscosity glass
      ionomer cement placed in posterior permanent teeth by means of the Atraumatic
      Restorative Treatment (ART) approach. One operator placed 167 single- and 107
      multiple-surface restorations in 43 high-risk caries pregnant women (mean decayed
      teeth = 9.8 +/- 5.5). Examinations were performed at 1-, 2-, and 10-year
      intervals according to ART criteria. In the last evaluation, the US Public Health
      Service (USPHS) criteria were also used. After 10 years, 129 restorations (47.1%)
      were evaluated and achieved a cumulative survival rate of 49.0% (SE 7.2%). The 10
      year survival of single- and multiple-surface ART restorations assessed using the
      ART criteria were 65.2% (SE 7.3%) and 30.6% (SE 9.9%), respectively. This
      difference was significant (jackknife SE of difference; p < 0.05). Using the
      USPHS criteria, the 10-year survival of single- and multiple-surface ART
      restorations were 86.5% and 57.6%, respectively. The primary causes of failure
      were total loss (9.3%) and marginal defects (5.4%). The survival rates observed,
      especially for the single-surface restorations, confirm the potential of the ART
      approach for restoring and saving posterior permanent teeth.

PMID- 20140471
TI  - Exploring the molecular basis for selective binding of Mycobacterium tuberculosis
      Asp kinase toward its natural substrates and feedback inhibitors: a docking and
      molecular dynamics study.
AB  - Tuberculosis (TB) is still a major public health problem, compounded by the human
      immunodeficiency virus (HIV)-TB co-infection and recent emergence of multidrug
      resistant (MDR) and extensively drug resistant (XDR)-TB. In this context,
      aspartokinase of mycobacterium tuberculosis has drawn attention for designing
      novel anti-TB drugs. Asp kinase is an enzyme responsible for the synthesis of 4
      phospho-L-aspartate from L-aspartate and involved in the branched biosynthetic
      pathway leading to the synthesis of amino acids lysine, threonine, methionine and
      isoleucine. An intermediate of lysine biosynthetic branch, mesodiaminopimelate is
      also a component of the peptidoglycan which is a component of bacterial cell
      wall. To interfere with the production of all these amino acids and cell wall, it
      is possible to inhibit Asp kinase activity. This can be achieved using Asp kinase
      inhibitors. In order to design novel Asp kinase inhibitors as effective anti-TB
      drugs, it is necessary to have an understanding of the binding sites of Asp
      kinase. As no crystal structure of the enzyme has yet been published, we built a
      homology model of Asp kinase using the crystallized Asp kinase from M.
      Jannaschii, as template structures (2HMF and 3C1M). After the molecular dynamics
      refinement, the optimized homology model was assessed as a reliable structure by
      PROCHECK, ERRAT, WHAT-IF, PROSA2003 and VERIFY-3D. The results of molecular
      docking studies with natural substrates, products and feedback inhibitors are in
      agreement with the published data and showed that ACT domain plays an important
      role in binding to ligands. Based on the docking conformations, pharmacophore
      model can be developed by probing the common features of ligands. By analyzing
      the results, ACT domain architecture, certain key residues that are responsible
      for binding to feedback inhibitors and natural substrates were identified. This
      would be very helpful in understanding the blockade mechanism of Asp kinase and
      providing insights into rational design of novel Asp kinase inhibitors for
      M.tuberculosis.

PMID- 20140472
TI  - Photodimerizations of hydroxy- and benzoylated 4-azachalcones and quantum
      chemical investigation of the reactions.
AB  - Photodimerization reactions of compounds 4-6 gave four new cyclobutane-containing
      compounds (7-9) with full control over the stereochemistry at the four
      stereogenic centers. These new cyclobutane-containing compounds had beta-truxinic
      (7a), delta-truxinic (7b and 9), and epsilon-truxillic (8) structures. However, o
      , m-, and p-hydroxy 4-azachalcones (1-3) did not give photochemical cyclization
      products under any conditions (in solvent or in their solid or molten states).
      Experimental data suggested the possibility of frontier orbital control over
      stereochemical behavior, so some theoretical calculations were performed. Full
      geometrical optimization of compounds 1-9 was performed via DFT B3LYP/6-31(+)G**,
      and their electronic structures were also investigated. The geometries of the
      singlet and triplet states were initially optimized by density functional theory
      (DFT) and the configuration interaction singles (CIS) B3LYP/3-21(+)G** level. An
      additional calculation was performed for the triplet state using the ground-state
      geometry. The possible photochemical dimerization products of compounds 7-9 (a-g)
      and the intrinsic reaction coordinates (IRCs) of the reactions of compounds 4-6
      were calculated theoretically by the DFT/3-21(+)G** method. The configurations
      (reactant, transition state, product, and reaction pathway) corresponding to the
      stationary points (minima or saddle points) were determined. The intrinsic
      reaction coordinates were followed to verify the energy profiles that connect
      each TS to the appropriate local minimum. The dimeric products expected from the
      calculations coincided with the dimers produced experimentally.

PMID- 20140473
TI  - Diffuse systemic sclerosis and autoimmune hepatitis: a unique association.
AB  - Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology
      characterized by continuing hepatocellular necrosis and inflammation that
      afflicts 100,000 to 200,000 persons in the United States. It is a rare
      manifestation of systemic sclerosis. Only about nine reports of this association
      have been previously reported in the literature. Importantly, all cases had the
      limited clinical form of systemic. The authors describe herein the first report
      of a patient with diffuse systemic sclerosis who was diagnosed with AIH with
      positive antimitochondrial antibody and had an excellent response to
      immunosuppressive drugs. We also briefly review the literature regarding this
      issue.

PMID- 20140474
TI  - Reliability and validity of the foot and ankle outcome score: a validation study
      from Iran.
AB  - The aims of this study were to culturally adapt and validate the Persian version
      of Foot and Ankle Outcome Score (FAOS) and present data on its psychometric
      properties for patients with different foot and ankle problems. The Persian
      version of FAOS was developed after a standard forward-backward translation and
      cultural adaptation process. The sample included 93 patients with foot and ankle
      disorders who were asked to complete two questionnaires: FAOS and Short-Form 36
      Health Survey (SF-36). To determine test-retest reliability, 60 randomly chosen
      patients completed the FAOS again 2 to 6 days after the first administration.
      Test-retest reliability and internal consistency were assessed using intraclass
      correlation coefficient (ICC) and Cronbach's alpha, respectively. To evaluate
      convergent and divergent validity of FAOS compared to similar and dissimilar
      concepts of SF-36, the Spearman's rank correlation was used. Dimensionality was
      determined by assessing item-subscale correlation corrected for overlap. The
      results of test-retest reliability show that all the FAOS subscales have a very
      high ICC, ranging from 0.92 to 0.96. The minimum Cronbach's alpha level of 0.70
      was exceeded by most subscales. The Spearman's correlation coefficient for
      convergent construct validity fell within 0.32 to 0.58 for the main hypotheses
      presented a priori between FAOS and SF-36 subscales. For dimensionality, the
      minimum Spearman's correlation coefficient of 0.40 was exceeded by most items. In
      conclusion, the results of our study show that the Persian version of FAOS seems
      to be suitable for Iranian patients with various foot and ankle problems
      especially lateral ankle sprain. Future studies are needed to establish stronger
      psychometric properties for patients with different foot and ankle problems.

PMID- 20140475
TI  - A case of Serratia granuloma in the soft tissue around the left kidney: a role of
      PTHrP in the formation of Serratia granuloma.
AB  - Serratia marcescens is an ubiquitous, saprophytic gram-negative bacillus that is
      associated with infections such as bacteremia, pneumonia and osteomyelitis.
      However, it has not been known to form granulomas. A 72-year-old man with a
      history of tricuspidal insufficiency, mitral insufficiency and ureterolithiasis
      presented with lumbago on the left side. He was admitted to our hospital, where
      abscess formation in the subcapsular space and perirenal fat space of the left
      kidney, and left renal calculi were identified by computed tomography of the
      abdomen. As infection and/or a tumor were suspected, nephrectomy was performed.
      The histopathological findings in the resected kidney indicated severe
      infiltration by inflammatory cells with lymphoid follicles in the interstitium,
      and the proliferation of mesangial cells and matrix in glomerulus. Furthermore,
      giant cell granulomas were observed in the soft tissue around the kidney. As an
      aerobic culture of the abscess from the granulomas only produced Serratia
      marcescens, these granulomas were diagnosed as Serratia marcescens granulomas. In
      addition, expressions of PTHrP and PTH/PTHrP-receptor were observed in the giant
      cells in Serratia granuloma, which suggested that PTHrP might be involved in
      giant cell formation in Serratia granuloma by autocrine and/or paracrine
      mechanisms.

PMID- 20140476
TI  - Cryopyrin-associated periodic syndromes: background and therapeutics.
AB  - Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations of the
      gene encoding the NLR family protein NLRP3, which together with caspase-1 and
      adaptor proteins constitutes a protein complex termed the inflammasome. In innate
      immune reactions, a variety of stimuli activate the NLRP3 inflammasome,
      triggering caspase-1 to process proIL-1 and thus to produce mature IL-1.
      Excessive production of IL-1 by monocytes/macrophages is the central
      pathophysiology of CAPS, and daily injection of the IL-1 receptor antagonist
      anakinra rapidly ameliorates the inflammatory symptoms in most cases.
      Furthermore, double-blind, placebo-controlled clinical trials have recently
      confirmed the efficacy and safety of rilonacept, a fusion protein of the IL-1
      receptor and IgG Fc, and canakinumab, a human anti-IL-1 monoclonal antibody, as
      novel long-lasting agents for treating CAPS.

PMID- 20140477
TI  - Characterization of Plasmodium falciparum co-chaperone p23: its intrinsic
      chaperone activity and interaction with Hsp90.
AB  - It is well known that the co-chaperone p23 regulates Hsp90 chaperone activity in
      protein folding. In Plasmodium falciparum, a putative p23 (Pfp23) has been
      identified through genome analysis, but its authenticity has remained unconfirmed
      since co-immunoprecipitation experiments failed to show its interaction with P.
      falciparum Hsp90 (PfHsp90). Thus, recombinant Pfp23 and PfHsp90 proteins purified
      from expressed clones were used in this study. It was clear that Pfp23 exhibited
      chaperone activity by virtue of its ability to suppress citrate synthase
      aggregation at 45 degrees C. Pfp23 was also shown to interact with PfHsp90 and to
      suppress its ATPase activity. Analyses of modeled Pfp23-PfHsp90 protein complex
      and site-directed mutagenesis further revealed strategically placed amino acid
      residues, K91, H93, W94 and K96, in Pfp23 to be crucial for binding PfHsp90.
      Collectively, this study has provided experimental evidence for the inherent
      chaperone function of Pfp23 and its interaction with PfHsp90, a sequel widely
      required for client protein activation.

PMID- 20140478
TI  - The impact on microtubule network of a bracovirus IkappaB-like protein.
AB  - Polydnavirus-encoded IkappaB-like proteins are similar to insect and mammalian
      IkappaB, and an immunosuppressive function in the host cells has been inferred to
      these proteins. Here we show that the expression of one of these IkappaB-like
      viral genes, the TnBVank1, in the Drosophila germline affects the localization of
      gurken, bicoid, and oskar mRNAs whose gene products are relevant for proper
      embryonic patterning. The altered localization of these mRNAs is suggestive of
      general defects in the intracellular, microtubule-based, trafficking routes.
      Analysis of microtubule motor proteins components such as the dynein heavy chain
      and the kinesin heavy chain revealed defects in the polarized microtubule
      network. Interestingly, the TnBVANK1 viral protein is uniformly distributed over
      the entire oocyte cortex, and appears to be anchored to the microtubule ends. Our
      data open up a very interesting issue on novel function(s) played by the ank gene
      family by interfering with cytoskeleton organization.

PMID- 20140480
TI  - Mesenteric vein thrombosis after laproscopic gastric sleeve procedure.

PMID- 20140479
TI  - Venous thromboembolism and cancer: a systematic review.
AB  - Venous thromboembolism (VTE) is a serious and potentially fatal disorder, which
      is often associated with a significant impact on the quality of life and on the
      clinical outcome of cancer patients. The pathophysiology of the association
      between thrombosis and cancer is complex: malignancy is associated with a
      baseline hypercoagulable state due to many factors including release of
      inflammatory cytokines, activation of the clotting system, expression of
      hemostatic proteins on tumor cells, inhibition of natural anticoagulants, and
      impaired fibrinolysis. Several risk factors, related to the patient, the disease,
      and the therapeutic interventions, have been identified as contributing to the
      occurrence of VTE. There is convincing evidence to recommend the use of heparins
      or fondaparinux for prevention of VTE in selected cancer patients, and,
      especially in some particular types of malignancies and cancer treatments.
      Management of VTE in patients with cancer is more challenging and bleeding
      complications associated with the use of anticoagulants are significantly higher
      in cancer patients than in those without malignancy. Important issues that need
      to be considered in all cases are interference with anticancer therapy,
      inconvenience of treatment, and impact on quality of life.

PMID- 20140481
TI  - Microbicidal effect of the lactoferrin peptides lactoferricin17-30,
      lactoferrampin265-284, and lactoferrin chimera on the parasite Entamoeba
      histolytica.
AB  - Entamoeba histolytica is a parasitic protozoan that produces amoebiasis, an
      intestinal disease characterized by ulcerative colitis and dysentery. In some
      cases, trophozoites can travel to the liver leading to hepatic abscesses and
      death. Recently, lactoferrin and lactoferricin B have been shown to be
      amoebicidal in axenic cultures. The aim of this work was to determine whether the
      lactoferrin-peptides lactoferricin amino acids 17-30, lactoferrampin amino acids
      265-284, and lactoferrin chimera which is a fusion product of the two peptides,
      are capable of producing a microbicidal effect to trophozoites of E. histolytica.
      We evaluated the killing effect of these peptides in growth kinetics carried out
      in axenic culture medium to which different concentrations of peptides were
      added. At 50 muM of peptide concentration, lactoferricin and lactoferrampin had a
      moderate amoebicidal effect, since a 45-50% of trophozoites remained viable at 24
      h culture. However, at 50 microM of the lactoferrin chimera 75% amoeba were
      killed whereas at 100 microM all cells died. These data indicate that of
      lactoferrin-peptides mainly the chimera have amoebicidal activity in a time- and
      concentration-dependent manner. The lactoferrin-peptides might be useful as
      therapeutic agents against amoebiasis and thereby diminish the use of
      metronidazole, which is extremely toxic for the host.

PMID- 20140482
TI  - Do clinicians working within the same context make consistent return-to-work
      recommendations?
AB  - INTRODUCTION: Healthcare providers play important roles in the process of making
      return-to-work (RTW) recommendations, which have important consequences for
      injured workers and their employers. We studied the inter-rater reliability of
      RTW determinations between clinicians in a specific workers' compensation
      setting. METHODS: Three case scenarios were given to clinicians working at one
      rehabilitation facility to examine consistency between clinicians in RTW
      recommendations. Additionally, we examined what information clinicians relied on
      to make decisions. Analysis included percentage agreement and other descriptive
      statistics. RESULTS: Thirty-six clinicians (13 physiotherapists, 10 occupational
      therapists, 8 exercise therapists, and 5 physicians) responded to the
      questionnaire. Subjects showed a high percentage agreement regarding RTW
      readiness on fracture and dislocation scenarios (97.2 and 94.4%, respectively),
      while agreement on a back pain scenario was modest (55.6%). In all cases, more
      than 50% of clinicians relied on biomedical information, such as physical
      examination. CONCLUSIONS: Clinicians demonstrated a high level of agreement
      (>94%) when making RTW recommendations for injuries with clear pathology.
      However, a lower level of agreement (56%) was observed for back pain where the
      etiology of pain and disability is often more complex. Clinicians most commonly
      recommended RTW with restrictions, underlining the importance of workplace
      accommodations and modified duties in facilitating resumption of work.

PMID- 20140483
TI  - Workplace health understandings and processes in small businesses: a systematic
      review of the qualitative literature.
AB  - INTRODUCTION: Small businesses (SBs) play an important role in global economies,
      employ half of all workers, and pose distinct workplace health problems. This
      systematic review of qualitative peer-reviewed literature was carried out to
      identify and synthesize research findings about how SB workplace parties
      understand and enact processes related to occupational health and safety (OHS).
      METHODS: The review was conducted as part of a larger mixed-method review and in
      consultation with stakeholders. A comprehensive literature search identified 5067
      studies. After screening for relevance, 20 qualitative articles were identified.
      Quality assessment led to 14 articles of sufficient quality to be included in the
      meta-ethnographic findings synthesis. RESULTS: This review finds that SBs have
      distinctive social relations of work, apprehensions of workplace risk, and
      legislative requirements. Eight themes were identified that consolidate knowledge
      on how SB workplace parties understand OHS hazards, how they manage risk and
      health problems, and how broader structures, policies and systems shape the
      practice of workplace health in SBs. The themes contribute to 'layers of
      evidence' that address SB work and health phenomena at the micro (e.g. employer
      or worker behavior), meso (e.g. organizational dynamics) and macro (e.g. state
      policy) levels. CONCLUSIONS: This synthesis details the unique qualities and
      conditions of SBs that merit particular attention from planners and occupational
      health policy makers. In particular, the informal workplace social relations can
      limit workers' and employers' apprehension of risk, and policy and complex
      contractual conditions in which SBs are often engaged (such as chains of
      subcontracting) can complicate occupational health responsibilities. This review
      questions the utility of SB exemptions from OHS regulations and suggests a
      legislative focus on the particular needs of SBs. It considers ways that workers
      might activate their own workplace health concerns, and suggests that more
      qualitative research on OHS solutions is needed. It suggests that answers to the
      SB OHS problems identified in this review might lie in third party interventions
      and improved worker representation.

PMID- 20140484
TI  - Employee retention and integrated disability management practices as demand side
      factors.
AB  - INTRODUCTION: Demand-side employment research on company policies and practices
      related to retention and absence and disability management (ADM) can contribute
      to our understanding of employment issues related to people with disabilities
      from the employers' perspective. AIM: To examine company ADM and retention
      practices and their effectiveness, as well as how these company policies and
      practices might influence hiring of people with disabilities. METHOD: Disability
      Management Employer Coalition employer members (N = 650) were surveyed by
      internet and the survey data were analyzed using descriptive statistics,
      correlation, and multiple regression. RESULTS: Ninety-five participants responded
      to the survey resulting in a response rate of 14%. Retention practice was found
      to be associated with retention effectiveness (r = .39, P < .01). Items most
      highly correlated with retention effectiveness address the provision of
      development opportunities to employees at every level, seeking the ideas and
      involvement of employees, and assuring they know how their work and performance
      support the mission. ADM practice was related to improving health and managing
      health conditions (r = .26, P < .05) and resolving disability and bringing back
      to work (r = .37, P < .01). Consistent RTW procedures (r = .21), employee
      oriented culture (r = .23), safety/risk prevention (r = .21), and very early
      intervention (r = .21) correlated with delaying/preventing employment exits
      related to health impairment. Retention practice, ADM practice, retention
      effectiveness, ADM effectiveness and disability attitudes comprised a model to
      predict the hiring of people with disabilities. The six-predictor model was
      significant, F(6, 86) = 13.54, P < .001 and accounted for 49% of the variance in
      hiring. However, only the disability attitudes factor (beta = .628, P < .001) was
      found to be significantly associated with hiring. CONCLUSIONS: Findings
      substantiate a positive relationship among retention practices, ADM practices and
      outcomes. Both are associated with retaining employees who develop potentially
      disabling conditions; but they are not directly connected to hiring people with
      disabilities. These appear to be two different policy and practice issues within
      most companies.

PMID- 20140485
TI  - Illness: a collection of poems.

PMID- 20140486
TI  - Barriers to cancer screening in Hmong Americans: the influence of health care
      accessibility, culture, and cancer literacy.
AB  - Hmong Americans face high cancer mortality rates even in comparison to their
      Asian American counterparts, and report low utilization of cancer screenings. To
      date, no study has been conducted on the cultural barriers this population faces
      in undergoing cancer screenings. A systematic review of the literature was
      conducted to examine the existing knowledge regarding the barriers to cancer
      screening for Hmong Americans. Potential barriers were identified from this
      examination to include: health access factors (type of health insurance,
      ethnicity of provider, low English proficiency, and years spent in the U.S.);
      cultural factors (belief in the spiritual etiology of diseases, patriarchal
      values, modesty, and mistrust of the western medical system); and cancer literacy
      factors (cancer and prevention illiteracy). Based on this review, potential
      cultural and ethnic group-specific prevention strategies and cancer health
      policies are discussed to address these barriers and enhance screening behavior
      among the Hmong.

PMID- 20140487
TI  - Sexual orientation versus age of onset as bases for typologies (subtypes) for
      gender identity disorder in adolescents and adults.
AB  - The most widely used and influential typologies for transsexualism and gender
      identity disorder (GID) in adolescents and adults employ either sexual
      orientation or age of onset of GID-related symptoms as bases for categorization.
      This review compares these two typological approaches, with the goal of
      determining which one should be employed for the diagnosis of GID in Adolescents
      or Adults (or its successor diagnosis) in the forthcoming revision of the
      Diagnostic and Statistical Manual of Mental Disorders (DSM). Typologies based on
      sexual orientation and age of onset of GID-related symptoms are roughly
      comparable in ease and reliability of subtype assignment. Typologies based on
      sexual orientation, however, employ subtypes that are less ambiguous and better
      suited to objective confirmation and that offer more concise, comprehensive
      clinical description. Typologies based on sexual orientation are also superior in
      their ability to predict treatment-related outcomes and comorbid psychopathology
      and to facilitate research. Commonly expressed objections to typologies based on
      sexual orientation are unpersuasive when examined closely. The DSM should
      continue to employ subtypes based on sexual orientation for the diagnosis of GID
      in Adolescents or Adults or its successor diagnosis.

PMID- 20140488
TI  - Finding the common core: evidence-based practices, clinically relevant evidence,
      and core mechanisms of change.
AB  - Improving the quality of children's mental health care can benefit from the
      adoption of evidence based and evidence informed treatments. However, the promise
      of moving science into practice is hampered by three core elements that need to
      be addressed in the current conversation among key stakeholders: (1) expanding
      our understanding of the clinical relevance of different types of evidence, (2)
      emphasizing the identification of core mechanisms of change, and (3) re
      conceptualizing what evidence-based practice means. This paper focuses on these
      elements in an attempt to find a common core among stakeholders that may create
      opportunities for more inclusive conversation to move the field of children's
      mental health care forward.

PMID- 20140489
TI  - The eye of the beholder: youths and parents differ on what matters in mental
      health services.
AB  - The goal of this study was to examine the degree to which youths and caregivers
      attend to different factors in evaluating their experiences with mental health
      programs. Youth (n = 251) receiving mental health services at community agencies
      and their caregivers (n = 275) were asked open-ended questions regarding the
      positive and negative aspects of the services. Qualitative analyses revealed some
      agreement but also divergence between youth and caregivers regarding the criteria
      by which services were evaluated and aspects of services that were valued most
      highly. Youths' positive comments primarily focused on treatment outcomes while
      caregivers focused more on characteristics of the program and provider. Youths'
      negative comments reflected dissatisfaction with the program, provider, and types
      of services offered while caregivers expressed dissatisfaction mainly with
      program characteristics. Results support the importance of assessing both youth
      and caregivers in attempts to understand the factors used by consumers to
      evaluate youth mental health services.

PMID- 20140490
TI  - Assessment of Social Information Processing in early childhood: development and
      initial validation of the Schultz Test of Emotion Processing-Preliminary Version.
AB  - Crick and Dodge's (Psychological Bulletin 115:74-101, 1994) social information
      processing model has proven very useful in guiding research focused on aggressive
      and peer-rejected children's social-cognitive functioning. Its application to
      early childhood, however, has been much more limited. The present study responds
      to this gap by developing and validating a video-based assessment tool
      appropriate for early childhood, the Schultz Test of Emotion Processing
      Preliminary Version (STEP-P). One hundred twenty-five Head Start preschool
      children participated in the study. More socially competent children more
      frequently attributed sadness to the victims of provocation and labeled
      aggressive behaviors as both morally unacceptable and less likely to lead to
      positive outcomes. More socially competent girls labeled others' emotions more
      accurately. More disruptive children more frequently produced physically
      aggressive solutions to social provocations, and more disruptive boys less
      frequently interpreted social provocations as accidental. The STEP-P holds
      promise as an assessment tool that assesses knowledge structures related to the
      SIP model in early childhood.

PMID- 20140491
TI  - Competing core processes in attention-deficit/hyperactivity disorder (ADHD): do
      working memory deficiencies underlie behavioral inhibition deficits?
AB  - The current study examined competing predictions of the working memory and
      behavioral inhibition models of ADHD. Behavioral inhibition was measured using a
      conventional stop-signal task, and central executive, phonological, and
      visuospatial working memory components (Baddeley 2007) were assessed in 14
      children with ADHD and 13 typically developing (TD) children. Bootstrapped
      mediation analyses revealed that the visuospatial working memory system and
      central executive both mediated the relationship between group membership (ADHD,
      TD) and stop-signal task performance. Conversely, stop-signal task performance
      mediated the relationship between group membership and central executive
      processes, but was unable to account for the phonological and visuospatial
      storage/rehearsal deficits consistently found in children with ADHD. Comparison
      of effect size estimates for both models suggested that working memory deficits
      may underlie impaired stop-signal task performance in children with ADHD. The
      current findings therefore challenge existing models of ADHD that describe
      behavioral inhibition as a core deficit of the disorder.

PMID- 20140492
TI  - Dopaminergic modulation of spiny neurons in the turtle striatum.
AB  - Intracellular recordings were obtained from brain slice preparation in neurons of
      the striatum of the turtle Trachemys scripta elegans, analogous to the mammalian
      striatum in its topographic organization, synaptic connectivity,
      cytoarchitecture, and neurochemistry. Here we show that these similarities extend
      to the electrophysiological properties of its neurons. Biocytin staining revealed
      that 85% of the recorded neurons were medium spiny neurons while 15% were aspiny
      neurons. Spiny neurons of the turtle resembled those found in the mammalian and
      avian striatum and express dopaminergic D(1) and D(2) class receptors. Because
      the striatum of the turtle receives a dense dopaminergic innervation from
      tegmental dopaminergic neurons we investigated the postsynaptic actions of
      selective dopamine receptor agonists in the excitability of spiny neurons. As in
      mammals and birds, activation of D(1)-receptors enhances, whereas activation of
      D(2)-receptors decreases the evoked discharge. Apparently, actions of dopamine
      agonists occur via the modulation of L-type (Ca(V)1) Ca2+-conductances. Strong
      cellular evidence suggests that the role of dopamine in the modulation of motor
      networks is preserved along vertebrate evolution.

PMID- 20140493
TI  - Development of spontaneous activity and response properties of primary lagenar
      neurons in the chick.
AB  - Here, we report for the first time developmental changes in spontaneous activity
      and in response properties of single nerve fibers from the macular chick lagena.
      Such aspects are important in order to get insight into the functional role of
      the lagena which remains undetermined. For this purpose, we used intracellular
      and extracellular single-unit recording techniques in an isolated inner ear
      preparation from the chicken at ages E15 and P1. At E15, afferent fibers
      displayed a low irregular spontaneous discharge rate (41 +/- 14 spikes/s, CV =
      1.17 +/- 0.1), which was replaced by regular high frequency spontaneous activity
      at P1 (CV = 0.48 +/- 0.8, 89 +/- 27 spikes/s). During the developmental period
      including E15, the percentage of silent neurons was 60% while that of P1 was 40%.
      The synaptic activity was higher at E15 than at P1. The action potential waveform
      generated at E15 had small amplitude and derivative depolarization, and
      consequently, a large duration in correlation with respect to action potential
      waveform at P1 (respectively: 53 +/- 2 vs. 65 +/- 3 mV, 60 +/- 11 vs. 109 +/- 20
      mV/ms, 3.6 +/- 0.4 vs. 1.1 +/- 0.12 ms). In addition, we recognized two response
      dynamics to the injection of current steps: phasic, or rapidly adapting neurons
      and tonic, or slowly adapting neurons. Our results indicate similar developmental
      processes for the lagena as described for the vestibular system in other species,
      in agreement with the known morphological characteristics of this otholitic end
      organ. The presence of more than one subtype of afferent neuron also correlates
      with previous reports on vestibular afferents with analogous electrophysiological
      properties, strongly suggesting the vestibular nature of the lagena.

PMID- 20140495
TI  - From anatomical 'competence' to complex capability. The views and experiences of
      UK tutors on how we should teach anatomy to medical students.
AB  - Developments in clinical education have recently challenged the identity of
      anatomy teaching and learning, leading to high profile debate over the potential
      implications for the competence levels of new doctors. However, the emphasis
      remains on methods of teaching, rather than a review of what well-rounded
      anatomical learning actually entails, and how teaching can address contemporary
      learning needs. This paper identifies and addresses some of these issues, drawing
      on expert views captured in qualitative research with anatomy tutors at twenty
      different medical schools in the UK. Three main themes emerging from our analysis
      are described: anatomy as a subject matter, the challenges of teaching or
      learning anatomy, and the use of teaching methods. We also detail how inductive
      analysis generated new hypotheses worthy of further consideration. These fall
      into two key categories: (1) improving anatomy curriculum design and (2)
      advancing anatomy education research.

PMID- 20140494
TI  - Quality of life among women recently diagnosed with invasive breast cancer: the
      Pathways Study.
AB  - Few studies have assessed quality of life (QOL) of women diagnosed with breast
      cancer within the first few weeks of their initial diagnosis. We describe QOL
      among 950 women recently diagnosed with invasive breast cancer. Starting in
      January 2006, we invited women aged > or =21 years who were diagnosed with first
      primary invasive breast cancer within Kaiser Permanente Northern California
      (KPNC) to enroll in the Pathways Study, a prospective study of breast cancer
      survivorship. QOL was measured using the Functional Assessment of Cancer Therapy
      Breast Cancer (FACT-B), along with sociodemographic and social support
      information. Clinical characteristics were obtained from the KPNC cancer registry
      and electronic medical record. We used multivariable linear regression models to
      identify factors associated with QOL scores calculated from the FACT-B. The mean
      age +/- SD of the sample was 59.6 years (+/-11.9 years), and the mean time +/-SD
      from diagnosis until interview was 8.0 weeks (+/-3.2 weeks). Younger age at
      diagnosis was associated with lower scores in all QOL domains (P < 0.01), and
      later stage at diagnosis was associated with lower scores in all domains (P <
      0.05) except for social well-being. Higher levels of social support were
      associated with higher QOL except for physical well-being (P < 0.05). These
      associations were stronger within 2 months of breast cancer diagnosis. Quality of
      life as influenced by a diagnosis of breast cancer is an important factor in
      cancer survivorship. Age, stage at diagnosis, and social support are key factors
      in this important variable.

PMID- 20140496
TI  - Immobilization of 293 cells using porous support particles for adenovirus vector
      production.
AB  - Adenovirus vector production by anchorage-independent 293 cells immobilized using
      porous biomass support particles (BSPs) was investigated in static and shake
      flask cultures for efficient large-scale production of adenovirus vectors for
      gene therapy applications. The density of cells immobilized within BSPs was
      evaluated by measuring their WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)
      5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) reduction activity. In
      shake-flask culture, 293-F cells, which were adapted to serum-free suspension
      culture, were not successfully retained within reticulated polyvinyl formal (PVF)
      resin BSPs (2 * 2 * 2 mm cubes) with matrices of relatively small pores (pore
      diameter 60 MUm). When the BSPs were coated with a cationic polymer
      polyethyleneimine, a high cell density of more than 10(7) cells cm(-3)-BSP was
      achieved in both static and shake-flask cultures with regular replacement of the
      culture medium. After infection with an adenovirus vector carrying the enhanced
      green fluorescent protein gene (Ad EGFP), the specific Ad EGFP productivity of
      the immobilized cells was comparable to the maximal productivity of non
      immobilized 293-F cells by maintaining favorable conditions in the culture
      environment.

PMID- 20140497
TI  - Assessment of the statistical significance of seasonal groundwater quality change
      in a karstic aquifer system near Izmir-Turkey.
AB  - The main objective of this study was to statistically evaluate the significance
      of seasonal groundwater quality change and to provide an assessment on the
      spatial distribution of specific groundwater quality parameters. The studied area
      was the Mount Nif karstic aquifer system located in the southeast of the city of
      Izmir. Groundwater samples were collected at 57 sampling points in the rainy
      winter and dry summer seasons. Groundwater quality indicators of interest were
      electrical conductivity (EC), nitrate, chloride, sulfate, sodium, some heavy
      metals, and arsenic. Maps showing the spatial distributions and temporal changes
      of these parameters were created to further interpret spatial patterns and
      seasonal changes in groundwater quality. Furthermore, statistical tests were
      conducted to confirm whether the seasonal changes for each quality parameter were
      statistically significant. It was evident from the statistical tests that the
      seasonal changes in most groundwater quality parameters were statistically not
      significant. However, the increase in EC values and aluminum concentrations from
      winter to summer was found to be significant. Furthermore, a negative correlation
      between sampling elevation and groundwater quality was found. It was shown that
      with simple statistical testing, important conclusions can be drawn from limited
      monitoring data. It was concluded that less groundwater recharge in the dry
      period of the year does not always imply higher concentrations for all
      groundwater quality parameters because water circulation times, lithology,
      quality and extent of recharge, and land use patterns also play an important role
      on the alteration of groundwater quality.

PMID- 20140498
TI  - Fluoride incidence in groundwater: a case study from Talupula, Andhra Pradesh,
      India.
AB  - Fluoride-rich groundwater is well known in granite aquifers in India and the
      world. This study examines the fluoride content of well water in different parts
      of Talupula area of Anantapur district, Andhra Pradesh. It also focuses on
      fluorides and their relationship to water-quality parameters and their impacts on
      humans through groundwater resources. Most parts of the area covered in this
      region are inherently enriched with fluorides threatening several ecosystems. The
      fluoride concentration ranges between 0.78 and 6.10 mg L-1. The alkaline pH and
      high bicarbonate are responsible for release of fluoride-bearing minerals into
      groundwater. The arid climate of the region, the granitic rocks and the low
      freshwater exchange due to periodical drought conditions are the factors
      responsible for the higher incidence of fluorides in the groundwater resources.
      Apart from these prevailing natural conditions, years of neglect and lack of
      restoration programs on terrestrial and aquatic environments have led to
      accumulative impacts on groundwater, soils, plants, and animals including humans.
      The people dependent on these groundwater resources are prone to dental fluorosis
      and mild skeletal fluorosis.

PMID- 20140499
TI  - Assessment of heavy metals in sediments from a typical catchment of the Yangtze
      River, China.
AB  - An intensive investigation was conducted to study the accumulation, speciation,
      and distribution of various heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in
      sediments from the Yangtze River catchment of Wuhan, China. The potential
      ecological risks posed by these heavy metals also were estimated. The median
      concentrations of most heavy metals (As, Cd, Cr, Cu, Ni, Pb, and Zn) were higher
      than the background values of soils in Wuhan and were beyond the threshold effect
      level (TEL), implying heavy metal contamination of the sediments. Carbonate-bound
      Cd and exchangeable Cd, both of which had high bioavailability, were 40.2% and
      30.5% of the total for Cd, respectively, demonstrating that Cd poses a high
      ecological risk in the sediments. The coefficients of the relationship among Pb,
      Hg, and Cu were greater than 0.797 using correlation analysis, indicating the
      highly positive correlation among these three elements. Besides, total organic
      carbon content played an important role in determining the behaviors of heavy
      metals in sediments. Principal component analysis was used to study the
      distribution and potential origin of heavy metals. The result suggested three
      principal components controlling their variability in sediments, which accounted
      for 36.72% (factor 1: Hg, Cu, and Pb), 28.69% (factor 2: Cr, Zn, and Ni), and
      19.45% (factor 3: As and Cd) of the total variance. Overall, 75% of the studied
      sediment samples afforded relatively low potential ecological risk despite the
      fact that generally higher concentrations of heavy metals relative to TEL were
      detected in the sediments.

PMID- 20140500
TI  - Geoprocessing applied to the assessment of environmental noise: a case study in
      the city of Sorocaba, Sao Paulo, Brazil.
AB  - Noise mapping has been used as an instrument for assessment of environmental
      noise, helping to support decision making on urban planning. In Brazil, urban
      noise is not yet recognized as a major environmental problem by the government.
      Besides, cities that have databases to drive acoustic simulations, making use of
      advanced noise mapping systems, are rare. This study sought an alternative method
      of noise mapping through the use of geoprocessing, which is feasible for the
      Brazilian reality and for other developing countries. The area chosen for the
      study was the central zone of the city of Sorocaba, located in Sao Paulo State,
      Brazil. The proposed method was effective in the spatial evaluation of equivalent
      sound pressure level. The results showed an urban area with high noise levels
      that exceed the legal standard, posing a threat to the welfare of the population.

PMID- 20140501
TI  - Attenuation of dissolved metals in neutral mine drainage in the Zambian
      Copperbelt.
AB  - Behaviour of metals like Cu and Co was studied in nearly neutral (pH >= 6.4) mine
      drainage seepage in a stream downgradient of a tailing dam at Chambishi site in
      the Copperbelt of Zambia. They are attenuated by precipitation of ferruginous
      ochres that incorporate significant quantities of metals. Using chemical
      analysis, X-ray powder diffraction and Mossbauer spectroscopy, we show that the
      ochres are composed mostly of amorphous ferric hydroxide. Close to the seepage
      face, the total Fe content of ochres increases due to precipitation of amorphous
      ferric hydroxide, but total Fe in sediment decreases further downstream. The
      stream then flows through wetland (dambo) where the remaining fraction of metals
      is removed. During rainy periods, increased flow rate may result in re-suspension
      of ochres, increasing thus the mobility of metals. Major ions like sulphate are
      conservative at the start of the dry period (May), but gypsum may probably
      precipitate later at the end of the dry period. Sequential extractions of bulk
      sediments indicate that Mn behaves differently to Fe, with a trend of increasing
      Mn with distance from the tailing dam. There is much more Fe than Mn in residual
      (Aqua Regia) fraction, indicating that amorphous ferric hydroxides are
      transformed to more crystalline phases deeper in sediment. Environmental impact
      of mine drainage is relatively limited due to its neutral character.

PMID- 20140502
TI  - The design of long-term air quality monitoring networks in urban areas using a
      spatiotemporal approach.
AB  - The implementation and maintenance of an air pollution monitoring program can be
      expensive and time consuming, especially when the aim is for long-term monitoring
      over a significant area. Consequently, it is essential that sites are optimized
      to provide the best representative cover while minimizing costs. In the past,
      there has been a tendency to locate sampling stations at pollution hot-spots.
      While this is acceptable for determining a maximum potential exposure or
      identifying the extent of a risk, there are limitations to this approach when
      assessing the potential impact of any future abatement strategies or determining
      the level of exposure outside the vicinity. This paper presents an approach in
      which representative air quality assessments can be undertaken for an urban area
      using the minimum number of measurement sites. A novel methodology is described
      that involves site selection to capture the maximum variance in measured
      pollutants, while minimizing spatiotemporal autocorrelation between the selected
      sites. A case study is presented for Yazd, Iran. Overall, the results show that
      the proposed methodology can be effective and enable the long-term monitoring of
      air pollution to be undertaken on a cost-effective basis in urban areas. In
      addition, there is the potential for the methodology to be utilized for other
      forms of pollution (e.g., water, soil, and noise).

PMID- 20140503
TI  - Mapping urban forest tree species using IKONOS imagery: preliminary results.
AB  - A stepwise masking system with high-resolution IKONOS imagery was developed to
      identify and map urban forest tree species/groups in the City of Tampa, Florida,
      USA. The eight species/groups consist of sand live oak (Quercus geminata), laurel
      oak (Quercus laurifolia), live oak (Quercus virginiana), magnolia (Magnolia
      grandiflora), pine (species group), palm (species group), camphor (Cinnamomum
      camphora), and red maple (Acer rubrum). The system was implemented with soil
      adjusted vegetation index (SAVI) threshold, textural information after running a
      low-pass filter, and brightness threshold of NIR band to separate tree canopies
      from non-vegetated areas from other vegetation types (e.g., grass/lawn) and to
      separate the tree canopies into sunlit and shadow areas. A maximum likelihood
      classifier was used to identify and map forest type and species. After IKONOS
      imagery was preprocessed, a total of nine spectral features were generated,
      including four spectral bands, three hue-intensity-saturation indices, one SAVI,
      and one texture image. The identified and mapped results were examined with
      independent ground survey data. The experimental results indicate that when
      classifying all the eight tree species/ groups with the high-resolution IKONOS
      image data, the identifying accuracy was very low and could not satisfy a
      practical application level, and when merging the eight species/groups into four
      major species/groups, the average accuracy is still low (average accuracy = 73%,
      overall accuracy = 86%, and kappa = 0.76 with sunlit test samples). Such a low
      accuracy of identifying and mapping the urban tree species/groups is attributable
      to low spatial resolution IKONOS image data relative to tree crown size, to
      complex and variable background spectrum impact on crown spectra, and to
      shadow/shaded impact. The preliminary results imply that to improve the tree
      species identification accuracy and achieve a practical application level in
      urban area, multi-temporal (multi-seasonal) or hyperspectral data image data
      should be considered for use in the future.

PMID- 20140504
TI  - Importance-performance analysis of municipal solid waste management in
      uncertainty.
AB  - The aim of this study was to evaluate and position the perceptions of importance
      and performance of municipal solid waste management aspects and criteria. The
      study results propose dependence relations among four aspects and 33 criteria
      pertaining to metropolitan Taipei. Evaluation was based on linguistically
      described preferences and multiple aspects and criteria analysis; in particular,
      applied fuzzy set theory was used to evaluate linguistic vagueness, and the
      analytic network process was applied for dependence relations among the aspects
      and criteria. In order to compile managerial implications and concluding remarks,
      importance-performance analysis was conducted, using several mathematical
      techniques applied to the objectives as well as the participation and input of
      professionals and academicians. Overall results and concluding remarks are
      discussed.

PMID- 20140505
TI  - Corrections for measurements of tritium in subterranean vapor using silica gel.
AB  - Hazardous contaminants buried within vadose zones can accumulate in soil gas. The
      concentrations and spatial extent of these contaminants are measured to evaluate
      potential transport to groundwater for public risk evaluation. Tritium is an
      important contaminant found and monitored for in vadose zones across numerous
      sites within the US nuclear weapons complex, including Los Alamos National
      Laboratory. The extraction, collection, and laboratory analysis of tritium from
      subterranean soil gas presents numerous technical challenges that have not been
      fully studied. Particularly, the lack of moisture in the soil gas in the vadose
      zone makes it difficult to obtain enough sample (e.g., > 5 g) to provide for the
      required measurement sensitivity, and often, only small amounts of moisture can
      be collected. Further, although silica gel has high affinity for water vapor and
      is prebaked prior to sampling, there is still sufficient residual moisture in the
      prebaked gel to dilute the relatively small amount of sampled moisture; thereby,
      significantly lowering the "true" tritium concentration in the soil gas. This
      paper provides an evaluation of the magnitude of the bias from dilution, provides
      methods to correct past measurements by applying a correction factor (CF), and
      evaluates the uncertainty of the CF values. For this, 10,000 Monte Carlo
      calculations were performed, and distribution parameters of CF values were
      determined and evaluated. The mean and standard deviation of the distribution of
      CF values were 1.53 +/- 0.36, and the minimum, median, and maximum values were
      1.14, 1.43, and 5.27, respectively.

PMID- 20140506
TI  - Information needs for siting new, and evaluating current, nuclear facilities:
      ecology, fate and transport, and human health.
AB  - The USA is entering an era of energy diversity, and increasing nuclear capacity
      and concerns focus on accidents, security, waste, and pollution. Physical buffers
      that separate outsiders from nuclear facilities often support important natural
      ecosystems but may contain contaminants. The US Nuclear Regulatory Commission
      (NRC) licenses nuclear reactors; the applicant provides environmental assessments
      that serve as the basis for Environmental Impact Statements developed by NRC. We
      provide a template for the types of information needed for safe siting of nuclear
      facilities with buffers in three categories: ecological, fate and transport, and
      human health information that can be used for risk evaluations. Each item on the
      lists is an indicator for evaluation, and individual indicators can be selected
      for specific region. Ecological information needs include biodiversity (species,
      populations, communities) and structure and functioning of ecosystems, habitats,
      and landscapes, in addition to common, abundant, and unique species and
      endangered and rare ones. The key variables of fate and transport are sources of
      release for radionuclides and other chemicals, nature of releases (atmospheric
      vapors, subsurface liquids), features, and properties of environmental media
      (wind speed, direction and atmospheric stability, hydraulic gradient, hydraulic
      conductivity, groundwater chemistry). Human health aspects include receptor
      populations (demography, density, dispersion, and distance), potential pathways
      (drinking water sources, gardening, fishing), and exposure opportunities
      (lifestyle activities). For each of the three types of information needs, we
      expect that only a few of the indicators will be applicable to a particular site
      and that stakeholders should agree on a site-specific suite.

PMID- 20140507
TI  - Comprehensive approach for the development of traffic noise prediction model for
      Jaipur city.
AB  - The main objective of the present study was to develop an empirical noise
      prediction model for the evaluation of equivalent noise level (Leq) in terms of
      equivalent traffic density number under heterogeneous traffic flow conditions.
      Ten commercial road networks are selected for monitoring and modeling. A new
      factor, i.e., equivalent number of light vehicles (EqLv) and for heavy vehicles
      (EqHv), has been used for evaluating the equivalent traffic density for each
      class of vehicles, and correlation graphs are plotted between equivalent traffic
      density with respect to EqLv and EqHv and observed equivalent noise level
      [Leq(o)] for the calculation of equivalent noise levels in terms of light
      vehicles [Leq(Lv)] and heavy vehicles [Leq(Hv)] for different identified
      locations as well as for the entire city. Furthermore, regression noise
      prediction equations have been developed between Leq(o), Leq(Lv), and Leq(Hv).
      After comparison of the results, it can be depicted that the light motor vehicles
      are the main source of noise pollution in the city and gives significantly higher
      correlation coefficient values. This model can be applied for the calculation of
      road traffic noise under interrupted traffic flow conditions in urban areas of
      Indian cities.

PMID- 20140508
TI  - Determination of total and partially extractable solid-bound element
      concentrations using collision/reaction cell inductively coupled plasma-mass
      spectrometry and their significance in environmental studies.
AB  - Determination of solid-bound element concentrations is an important initial step
      in environmental studies especially for assessment of contamination level, and of
      origin, relative mobility, and fate of contaminants. This study revealed that a
      relatively new collision/reaction cell inductively coupled plasma-mass
      spectrometry is a potent tool for determining total and partially extractable
      solid-bound element (V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, and Pb) concentrations in
      a complex matrix solution containing HF and/or HCl. Six different extraction
      methods commonly used for environmental monitoring studies were tested for their
      bias and variability using estuarine and marine standard reference materials.
      Microwave-assisted methods based on concentrated [HNO3] or [HNO3 + HF (4:1)] and
      [HNO3 + HF + HCl (10:3:2)] were applied for determining pseudo-total and total
      element concentrations, respectively. Dilute-acids (1 M HNO3, 1 M HCl, and 0.5 M
      HCl) were utilized in single-step partial extraction protocols. Except the 0.5 M
      HCl cold-extraction method which was performed at room temperature, other partial
      extraction protocols used microwave-digestion. This study demonstrated that the
      use of microwave-assisted methods in studies aimed at determining the non
      residual, non-specific extractable fractions of elements in solid environmental
      samples may result in overestimation, and thus needs to be re-examined. We
      believe that the cold extraction method will play a significant role in future
      environmental monitoring studies. Nevertheless, results of the cold extraction
      method not accompanied with total element concentrations have limited value, as
      the amount of extraction may vary significantly with the nature (origin) of the
      elements, and with the types of the samples. Therefore, we suggest combining
      microwave-assisted total digestion and 0.5 M HCl cold-extraction methods as a
      relatively cost- and time-effective, environmentally sound screening procedure
      for routine environmental monitoring programs involving a large number of samples
      from diverse geological and anthropogenic settings.

PMID- 20140509
TI  - Multi-year monitoring of estuarine sediments as ultimate sink for DDT, HCH, and
      other organochlorinated pesticides in Argentina.
AB  - Forty-nine superficial sediment samples used in this study were collected from
      eight sites in the Bahia Blanca Estuary, located in the Buenos Aires Province
      southwest, Argentina, in a period between April 2005 and March 2009, to assess
      the concentration levels, spatial and seasonal distribution, and putative input
      sources of 18 selected organochlorine pesticides (OCs), following UNEP-IAEA
      procedures. Average concentration levels in sediments ranged between 3.54 and
      63.79 ng g-1, d.w. (mean = 15.99 ng g-1, d.w.), for ?OCs, and from nondetectable
      to 8.03 ng g-1, d.w. (mean = 2.16 ng g-1, d.w.), and from nondetectable to 3.20
      ng g-1 (mean = 0.97 ng g-1, d.w.) for hexachlorocyclohexanes (HCHs) and
      dichlorodiphenyltrichloroethanes (DDTs), respectively. Principal component
      analysis allowed the classification of sampling sites according to the main OCs
      inputs over the estuary. In comparison to other worldwide locations and to the
      world coastal sediment concentrations range, sediment DDTs and HCHs levels were
      in the low range; on the opposite, ?OCs average was in the medium range. OCs
      seasonal distribution was found to be highly correlated with the precipitations
      seasonality and sowing seasons in the adjacent agriculture fields. In addition,
      an ecotoxicological risk assessment pointed industrial and agriculture catchment
      zones with intermediate probability of adverse effects to biota, while the city
      sewage outfall was classified with none indication of an immediate threat. Data
      indicated that the estuary sediments were functioning as a sink for persistent OC
      pesticides (either in use or banned), however, it was found a declining trend on
      their environmental burden.

PMID- 20140510
TI  - Spatial distribution of metals in top soils of Islamabad City, Pakistan.
AB  - Present study was conducted in rapidly growing city Islamabad, and surface soils
      were collected from three major land cover types viz., built-up, drain side, and
      green areas. A total of seven physicochemical parameters and 11 metals were
      determined in surface soils. Factor analysis based on principal component
      analysis explained total variance of 68.0%, 64.5%, and 60.2% of three land cover
      types and showed high loadings for major elements (Mg and K) in built-up and
      green area and Fe in drain side. Top soil pollution index was carried out by
      using geo-accumulation index and metal pollution index (MPI6). Concentration of
      major elements (Ca, Mg, Na, K) in surface soils is derived by parent material,
      whereas concentration of Fe, Ni, Pb, and Zn were mainly related with
      anthropogenic sources. Geostatistical methods such as kirging identified hotspot
      areas of metal contamination by Pb, Ni, and Zn in built-up areas influenced
      mainly by vehicular emissions and waste disposal. The results stresses that land
      clearing should be avoided to reduce contamination and management of urban soils.

PMID- 20140511
TI  - Effects of first postpartum progesterone rise, metabolites, milk yield, and body
      condition score on the subsequent ovarian activity and fertility in lactating
      Holstein dairy cows.
AB  - Seventy multiparous healthy lactating Holstein cows (fat-corrected milk yield =
      7,561.8 kg) were monitored from 14 days before to 70 days after calving.
      Transrectal ultrasound scanning was performed twice weekly from 7 to 65 days
      postpartum. Blood samples were also collected twice weekly to measure serum P(4)
      and biweekly to detect serum beta-hydroxybutyrate (betaHB) and nonesterified
      fatty acid (NEFA) concentrations. Body condition score (BCS) was taken biweekly
      after calving. Based on the serum P(4) profile of 59 cows (11 cows were excluded
      due to the occurrence of postpartum diseases) studied, 27 (45.8%) had normal
      ovarian activity, while 21 (35.6%), six (10.1%), three (5.1%), and two (3.4%) had
      delayed ovulation (DOV), prolonged luteal phase (PLP), short luteal phase (SLP),
      and cessation of ovarian activity, respectively. Cows with PLP had an earlier
      ovulation compared to that of cows with normal ovarian activity (23.16 +/- 4.02
      vs 31.9 +/- 8.35 days; P < 0.05). PLP cows also had a greater mean +/- standard
      deviation peak milk yield (44.2 +/- 5.8 vs 37.2 +/- 5.7 kg/day, 75 days
      postpartum; P < 0.05) than cows with normal postpartum ovarian activity. The PLP
      group also had greater milk production in the previous lactation period. Logistic
      regression analysis indicated that cows with P(4) concentration > or =1 ng/ml on
      day 24 after calving were more at risk for PLP by 1.1 for each 1 kg increase in
      mean peak milk yield during 75 days after calving. BCS was lower in cows with DOV
      compared to that of cows with normal ovarian activity at any time after calving
      (P < 0.05). Serum betaHB concentrations in DOV cows were significantly higher
      than that of normal cows on day 42 after calving (0.69 +/- 0.29 vs 0.54 +/- 0.12
      mmol/L, P < 0.05). No significant difference was found in the mean concentrations
      of NEFA between cows in different groups at any time after calving (P > 0.05).
      The concentrations of P(4) on days 28 and 31 were negatively correlated with
      betaHB concentration on day 42 after calving in cows with normal ovarian activity
      (R = -0.44, P = 0.02). In conclusion, these findings suggest that early ovulation
      and hence early postpartum P(4) rise in addition to the high milk production
      could partly be responsible for the occurrence of PLP in dairy cows.

PMID- 20140512
TI  - Generalizations about bacteriology: thermodynamic, open systems, genetic
      instructions, and evolution.
AB  - Biological generalizations about bacteriology are discussed to provide a broad
      perspective of what we know about bacteria. Bacteriology (and possibly all
      biology) from an overall perspective can be researched and understood as
      observations and experimentations on mass and energy, which are themselves the
      products of evolutionary change for about 3.5-3.9 billion years. All organisms
      have mass, transform, store and use biochemical energy and obey the most
      fundamental of all laws--the laws of thermodynamics. Bacteria can be viewed as
      semi-permeable, thermodynamically open systems of mass, controlled by relatively
      small amounts of genetic instructions with lower entropy than their higher
      entropy, surrounding environments. Some fundamental properties describing
      bacterial life are also presented.

PMID- 20140513
TI  - Microbial engineering of dehydro-amino acids and lanthionines in non-lantibiotic
      peptides.
AB  - This minireview focuses on the use of bacteria to introduce dehydroresidues and
      (methyl)lanthionines in (poly)peptides. It mainly describes the broad
      exploitation of bacteria containing lantibiotic enzymes for the engineering of
      these residues in a wide variety of peptides in particular in peptides unrelated
      to lantibiotics. Lantibiotic dehydratases dehydrate serines and threonines
      present in peptides preceded by a lantibiotic leader peptide thus forming
      dehydroalanine and dehydrobutyrine, respectively. These dehydroresidues can be
      coupled to cysteines thus forming (methyl)lanthionines. This coupling is
      catalysed by lantibiotic cyclases. The design, synthesis, and export of
      microbially engineered dehydroresidue and or lanthionine-containing peptides in
      non-lantibiotic peptides are reviewed, illustrated by some examples which
      demonstrate the high relevance of these special residues. This minireview is the
      first with special focus on the microbial engineering of nonlantibiotic peptides
      by exploiting lantibiotic enzymes.

PMID- 20140514
TI  - Susceptibility of Candida biofilms to histatin 5 and fluconazole.
AB  - Candida-associated denture stomatitis has a high rate of recurrence. Candida
      biofilms formed on denture acrylic are more resistant to antifungals than
      planktonic yeasts. Histatins, a family of basic peptides secreted by the major
      salivary glands in humans, especially histatin 5, possess significant antifungal
      properties. We examined antifungal activities of histatin 5 against planktonic or
      biofilm Candida albicans and Candida glabrata. Candida biofilms were developed on
      poly(methyl methacrylate) discs and treated with histatin 5 (0.01-100 microM) or
      fluconazole (1-200 microM). The metabolic activity of the biofilms was measured
      by the XTT reduction assay. The fungicidal activity of histatin 5 against
      planktonic Candida was tested by microdilution plate assay. Biofilm and
      planktonic C. albicans GDH18, UTR-14 and 6122/06 were highly susceptible to
      histatin 5, with 50% RMA (concentration of the agent causing 50% reduction in the
      metabolic activity; biofilm) of 4.6 +/- 2.2, 6.9 +/- 3.7 and 1.7 +/- 1.5 microM,
      and IC(50) (planktonic cells) of 3.0 +/- 0.5, 2.6 +/- 0.1 and 4.8 +/- 0.5,
      respectively. Biofilms of C. glabrata GDH1407 and 6115/06 were less susceptible
      to histatin 5, with 50% RMA of 31.2 +/- 4.8 and 62.5 +/- 0.7 microM,
      respectively. Planktonic C. glabrata was insensitive to histatin 5 (IC(50) > 100
      microM). Biofilm-associated Candida was highly resistant to fluconazole in the
      range 1-200 microM; e.g. at 100 microM only approximately 20% inhibition was
      observed for C. albicans, and approximately 30% inhibition for C. glabrata. These
      results indicate that histatin 5 exhibits antifungal activity against biofilms of
      C. albicans and C. glabrata developed on denture acrylic. C. glabrata is
      significantly less sensitive to histatin 5 than C. albicans.

PMID- 20140515
TI  - Knowledge of cardiovascular risk factors in West African refugee women living in
      Western Australia.
AB  - As obesity and cardiovascular disease are elevated in refugees who have migrated
      recently to Western countries, barriers to healthy eating and exercise were
      investigated in West African women who had entered Australia recently as
      refugees. Questionnaires on diet and exercise were administered to convenience
      samples of 51 West African women and 100 Australian women. Eighty percent of the
      West African women were overweight or obese compared with 49% of Australian
      women. The West African women were less clear about nutritional guidelines and
      had more misconceptions about exercise than the Australian women. BMI increased
      with age in both groups, and increased with fewer years at school and the number
      of internal barriers to exercise in Australian women. Dietary changes, limited
      nutritional knowledge of Western foods, a sedentary lifestyle, and barriers to
      participating in physical activity programmes may increase vulnerability to
      obesity and cardiovascular disease in West African women who have entered
      Australia recently as refugees.

PMID- 20140516
TI  - Antenatal screening for mother to child infections in immigrants and residents:
      the case of toxoplasmosis in northern Italy.
AB  - In Italy, serological screening is recommended to prevent congenital
      toxoplasmosis as part of the antenatal care protocol. Our study investigates (1)
      adherence to screening among Italian and migrant women and (2) specific T. gondii
      seroprevalence among hospitalized puerperas in Brescia and Udine, in northern
      Italy. All migrants (Group B) and a random Italian sample (Group A) filled in a
      questionnaire. Serological screening was rated as adequate when performed before
      conception or by the 12th week of gestation, and periodically repeated during
      pregnancy whenever negative. Nine hundred and twenty-two (922) puerperas were
      enrolled (Group A: 743; Group B: 179). Mean gestational age at first antenatal
      visit was 9.3 week, significantly more delayed in migrants (11.2w vs 8.9w; P <
      0.0001). Toxoplasmosis was mentioned as a potential vertically transmitted
      infection by 380/922 (41.2%), but only by 13.4% of migrants (P < 0.0001). Anti
      Toxoplasma IgG-Ab tested positive in 319/892 (35.8%), while the information was
      missing for 9 and 21 women resulted untested. Patients from northern Africa had
      an higher (AOR 3.63%; P = 0.002), while Asian patients a lower (AOR 0.33; P =
      0.045) probability of being immune. A late screening was recorded in 115/848
      (13.6%) women (Group A: 9.35%; Group B: 31.9%; P < 0.0001) and 82.1% of eligible
      migrants were not correctly monitored for toxoplasmosis during pregnancy. A late
      toxoplasma serological test in migrant women precludes the timely application of
      preventive measure and may represent an indicator of suboptimal antenatal care.

PMID- 20140517
TI  - Utilisation of hospital services in Italy: a comparative analysis of immigrant
      and Italian citizens.
AB  - In Italy, immigrants from Less Developed Countries (LDCs) have doubled every 10
      years since the 1970s and this number grew to 330,000 at the end of 1981, and to
      more than 1,300,000 in 2001. As the presence of immigrants increases, it becomes
      ever more important to assess their health needs and utilisation of health
      services, in order to promote adequate programmes and policies. This study was
      aimed to compare the patterns of hospital use by immigrants from LDCs living in
      the Lazio Region, Italy, with those of the resident Italians. The study was based
      on the hospital discharge data collected by the Lazio Region Hospital Information
      System. Discharges of immigrants from acute hospitals in Lazio during 2005 were
      compared with discharges of resident Italians. Age- and sex-specific
      hospitalisation rates (per 1,000) were also calculated for legal immigrants and
      Italians aged 18 years and over. Of 56,610 foreign patients from LCDs admitted to
      hospitals in Lazio during 2005, 88% were legally residing in the region. The
      immigrants were younger than the Italians (mean age 30.6 and 51.7 years,
      respectively), more than half were female and single, and about 1/3 had studied
      for 9 or more years. Among males, a similar pattern of hospital use by age was
      observed for foreigners and Italians, with the rates for foreigners in acute care
      being higher among young people (due to traumatic accidents) and lower among the
      oldest. Differently, among foreign females, the admission rates for both acute
      and day care settings varied with women's age, the pattern of hospital use being
      strongly influenced by reproductive events. The main reason for hospitalisation
      of foreign males in acute care was injuries (approximately 1/4 of all
      discharges), and in day care was neoplasms; among females, more than half of the
      admissions were for childbirth in acute or induced abortions in day care.
      Injuries for males and induced abortions for females were identified as critical
      areas for migrants' health, in which public health interventions may be promoted.

PMID- 20140518
TI  - Numerical simulations of ethacrynic acid transport from precorneal region to
      trabecular meshwork.
AB  - Topical application of drugs for treatment of intraocular diseases is often
      limited by inadequate transport and induced toxicity in corneal tissues. To
      improve the drug delivery, a mathematical model was developed to numerically
      simulate the transport process of ethacrynic acid (ECA), a potential drug for
      glaucoma treatment, in the anterior segment of a typical human eye. The model
      considered diffusion of ECA in all tissues and the aqueous humor (AH) as well as
      convection of ECA in the AH. The simulation results showed that ECA concentration
      in the eye depended on the rate of AH production, the half-life of ECA in the
      precorneal tear film, and the transport parameters in the model. In addition, the
      main pathway for ECA clearance from the eye was the trabecular meshwork (TM) and
      the rate of clearance was approximately proportional to the AH production rate.
      The model predicted that the most effective approach to improving topical drug
      delivery was to prolong its half-life in the precorneal tear film. These
      simulation results and model prediction, which could be verified experimentally,
      might be useful for improving delivery of ECA and other therapeutic agents to the
      TM as well as other tissues in the anterior segment of the eye.

PMID- 20140519
TI  - From cellular mechanotransduction to biologically inspired engineering: 2009
      Pritzker Award Lecture, BMES Annual Meeting October 10, 2009.
AB  - This article is based on a lecture I presented as the recipient of the 2009
      Pritzker Distinguished Lecturer Award at the Biomedical Engineering Society
      annual meeting in October 2009. Here, I review more than thirty years of research
      from my laboratory, beginning with studies designed to test the theory that cells
      use tensegrity (tensional integrity) architecture to stabilize their shape and
      sense mechanical signals, which I believed to be critical for control of cell
      function and tissue development. Although I was trained as a cell biologist, I
      found that the tools I had at my disposal were insufficient to experimentally
      test these theories, and thus I ventured into engineering to find critical
      solutions. This path has been extremely fruitful as it has led to confirmation of
      the critical role that physical forces play in developmental control, as well as
      how cells sense and respond to mechanical signals at the molecular level through
      a process known as cellular mechanotransduction. Many of the predictions of the
      cellular tensegrity model relating to cell mechanical behaviors have been shown
      to be valid, and this vision of cell structure led to discovery of the central
      role that transmembrane adhesion receptors, such as integrins, and the
      cytoskeleton play in mechanosensing and mechanochemical conversion. In addition,
      these fundamental studies have led to significant unexpected technology fallout,
      including development of micromagnetic actuators for non-invasive control of
      cellular signaling, microfluidic systems as therapeutic extracorporeal devices
      for sepsis therapy, and new DNA-based nanobiotechnology approaches that permit
      construction of artificial tensegrities that mimic properties of living materials
      for applications in tissue engineering and regenerative medicine.

PMID- 20140520
TI  - Bioengineering the skin-implant interface: the use of regenerative therapies in
      implanted devices.
AB  - This discussion and review article focuses on the possible use of regenerative
      techniques applied to the interfaces between skin and medical implants. As is
      widely known, the area of contact between an implant and the skin--the skin
      implant interface--is prone to recurrent and persistent problems originated from
      the lack of integration between the material of the implant and the skin.
      Producing a long-term successful biointerface between skin and the implanted
      device is still an unsolved problem. These complications have prevented the
      development of advanced prosthetics and the evolution of biointegrated devices
      with new technologies. While previous techniques addressing these issues have
      relied mostly on the coating of the implants or the modification of the topology
      of the devices, recent in vitro developed techniques have shown that is possible
      to introduce biocompatible and possibly regenerative materials at the skin-device
      interface. These techniques have also shown that the process of delivering the
      materials has biological effects on the skin surrounding the implant, thus
      converting bioinert into bioactive, dynamic interfaces. Given that the best
      clinical outcome is the long-term stabilization and integration of the soft
      tissue around the implant, this article presents the basis for the selection of
      regenerative materials and therapies for long-term use at the skin-device
      interface, with focus on the use of natural biopolymers and skin cell
      transplantation.

PMID- 20140522
TI  - Cell death beyond worms, flies and humans: Unusual model systems for cell death
      research.

PMID- 20140521
TI  - Apoptotic cell-based therapies against transplant rejection: role of recipient's
      dendritic cells.
AB  - One of the ultimate goals in transplantation is to develop novel therapeutic
      methods for induction of donor-specific tolerance to reduce the side effects
      caused by the generalized immunosuppression associated to the currently used
      pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis
      exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)
      presenting cells (APC) like dendritic cells (DC) and macrophages. This
      observation led to the idea that apoptotic cell-based therapies could be employed
      to deliver donor-Ag in combination with regulatory signals to recipient's APC as
      therapeutic approach to restrain the anti-donor response. This review describes
      the multiple mechanisms by which apoptotic cells down-modulate the immuno
      stimulatory and pro-inflammatory functions of DC and macrophages, and the role of
      the interaction between apoptotic cells and APC in self-tolerance and in
      apoptotic cell-based therapies to prevent/treat allograft rejection and graft
      versus-host disease in murine experimental systems and in humans. It also
      explores the role that in vivo-generated apoptotic cells could have in the
      beneficial effects of extracorporeal photopheresis, donor-specific transfusion,
      and tolerogenic DC-based therapies in transplantation.

PMID- 20140523
TI  - Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term
      pulmonary function in patients treated with recombinant human N
      acetylgalactosamine 4-sulfatase.
AB  - Pulmonary function is impaired in untreated mucopolysaccharidosis type VI (MPS
      VI). Pulmonary function was studied in patients during long-term enzyme
      replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB; rhN
      acetylgalactosamine 4-sulfatase). Pulmonary function tests prior to and for up to
      240 weeks of weekly infusions of rhASB at 1 mg/kg were completed in 56 patients
      during Phase 1/2, Phase 2, Phase 3 and Phase 3 Extension trials of rhASB and the
      Survey Study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)
      and, in a subset of patients, maximum voluntary ventilation (MVV), were analyzed
      as absolute volume in liters. FEV1 and FVC showed little change from baseline
      during the first 24 weeks of ERT, but after 96 weeks, these parameters increased
      over baseline by 11% and 17%, respectively. This positive trend compared with
      baseline continued beyond 96 weeks of treatment. Improvements from baseline in
      pulmonary function occurred along with gains in height in the younger group (5.5%
      change) and in the older patient group (2.4% change) at 96 weeks. Changes in MVV
      occurred earlier within 24 weeks of treatment to approximately 15% over baseline.
      Model results based on data from all trials showed significant improvements in
      the rate of change in pulmonary function during 96 weeks on ERT, whereas little
      or no improvement was observed for the same time period prior to ERT. Thus,
      analysis of mean percent change data and longitudinal modeling both indicate that
      long-term ERT resulted in improvement in pulmonary function in MPS VI patients.

PMID- 20140525
TI  - Assessment of clinical practices among cancer genetic counselors.
AB  - Various models of cancer genetics service delivery have been published, and
      practice guidelines were set forth by the National Society of Genetic Counselors
      (NSGC) in 2004. While the demand for services has increased, there has not been a
      comprehensive study of current practice models. An online survey of the NSGC
      Familial Cancer Risk Counseling Special Interest Group was conducted to study
      current methods of providing clinical cancer genetics services. Respondents were
      asked to quantify patient volume, support staff availability, and physician
      involvement in cases. Two case examples were used to further describe current
      practices including the number of genetic counseling tasks performed, time spent
      in these tasks, and number of in-person visits versus phone encounters. Although
      published cancer genetic counseling guidelines advise a 3-visit model (initial
      consult, sample draw, and result disclosure), 29.3% of respondents have adopted a
      1-visit model, where the sample is drawn at the first visit and phone disclosure
      replaces the third visit. The content of the initial consult does not vary
      significantly, and is consistent with the NSGC practice guidelines. Furthermore,
      56% report spending >15 min on case preparation, and 27 respondents self-reported
      redundancy in tasks such as documentation. It appears that a proportion of
      genetic counselors are following a new model of service delivery. However,
      insufficient documentation and case preparation are apparent, and many
      respondents reported lack of support staff as a barrier to efficient patient
      care. Factors contributing to the variability in current practice, and how they
      affect efficiency, require further study.

PMID- 20140524
TI  - A comparison of echocardiography to invasive measurement in the evaluation of
      pulmonary arterial hypertension in a rat model.
AB  - Pulmonary arterial hypertension (PAH) is a life-threatening condition
      characterized by progressive elevation in pulmonary artery pressure (PAP) and
      total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques
      have allowed the development of new echocardiographic parameters to evaluate
      disease progression. However, there are no reports comparing the diagnostic
      performance of these non-invasive parameters to each other and to invasive
      measurements. Therefore, we investigated the diagnostic yield of
      echocardiographically derived TPVR and Doppler parameters of PAP in screening and
      measuring the severity of PAH in a rat model. Serial echocardiographic and
      invasive measurements were performed at baseline, 21 and 35 days after
      monocrotaline-induction of PAH. The most challenging echocardiographic derived
      TPVR measurement had good correlation with the invasive measurement (r = 0.92, P
      < 0.001) but also more simple and novel parameters of TPVR were found to be
      useful although the non-invasive TPVR measurement was feasible in only 29% of the
      studies due to lack of sufficient tricuspid valve regurgitation. However,
      echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT)
      and deceleration (PAD), were measurable in all animals, and correlated with
      invasive PAP (r = -0.74 and r = 0.75, P < 0.001 for both). Right ventricular
      thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001
      for both). Observer variability of the invasive and non-invasive parameters was
      low except in tissue-Doppler derived isovolumetric relaxation time. These non
      invasive parameters may be used to replace invasive measurements in detecting
      successful disease induction and to complement invasive data in the evaluation of
      PAH severity in a rat model.

PMID- 20140526
TI  - Can self-esteem, mastery and perceived stigma predict long-term adjustment in
      women carrying a BRCA1/2-mutation? Evidence from a multi-center study.
AB  - Little is known about protective and vulnerability factors of long-term
      adjustment with BRCA1/2 carrier status. Specifically, the role of personal
      resources and perceptions of stigmatization have not been studied in the context
      of adjustment with hereditary breast cancer. The present study, therefore,
      explored associations of personal resources and stigma with cancer-specific
      anxiety in female BRCA1/2-carriers within a cross-sectional multi-center study.
      Participants (n = 237) had received carrier notification between 4 months and 8
      years before data collection and experienced a low level of cancer-related
      anxiety on average. Younger age was associated with both higher perceptions of
      stigma (P = .002) and cancer-specific anxiety (P = .034). Time since receiving
      test results, affected status, having undergone prophylactic mastectomy or
      prophylactic oophorectomy was not associated with demographic or psychological
      variables. Global self-esteem (P = .002) and mastery (P < .001) were associated
      with fewer intrusive and avoidant thoughts, whereas stigma was associated with
      more (P < .001). Time since test result receipt did not moderate relations of
      self-esteem, mastery or stigma and cancer-specific anxiety. Cancer-specific
      anxiety did not vary as a function of time since carrier notification. Hence
      cancer-specific distress may be explained by past and ongoing experiences of
      cancer in the family rather than by the time point of carrier notification.
      Psychological interventions may benefit from specifically addressing feelings of
      stigmatization, and promoting self-worth and personal control in order to affect
      cancer-specific anxiety.

PMID- 20140527
TI  - Is lymphadenectomy a predictor or savior for patients with gastric cancer?

PMID- 20140528
TI  - The effect of providing information about lymphedema on the cognitive and symptom
      outcomes of breast cancer survivors.
AB  - BACKGROUND: Despite recent advances in breast cancer treatment, breast cancer
      related lymphedema (BCRL) continues to be a significant problem for many
      survivors. Some BCRL risk factors may be largely unavoidable, such as mastectomy,
      axillary lymph node dissection (ALND), or radiation therapy. Potentially
      avoidable risk factors unrelated to breast cancer treatment include minor upper
      extremity infections, injury or trauma to the arm, overuse of the limb, and air
      travel. This study investigates how providing information about BCRL affects the
      cognitive and symptomatic outcome of breast cancer survivors. METHODS: Data were
      collected from 136 breast cancer survivors using a Demographic and Medical
      Information interview instrument, a Lymphedema Education Status interview
      instrument, a Knowledge Test for cognitive outcome, and the Lymphedema and Breast
      Cancer Questionnaire for symptom outcome. Data analysis included descriptive
      statistics, t tests, chi-square (chi(2)) tests, and regression. RESULTS: BCRL
      information was given to 57% of subjects during treatment. The mean number of
      lymphedema-related symptoms was 3 symptoms. Patients who received information
      reported significantly fewer symptoms and scored significantly higher in the
      knowledge test. After controlling for confounding factors, patient education
      remains an additional predictor of BCRL outcome. Significantly fewer women who
      received information about BCRL reported swelling, heaviness, impaired shoulder
      mobility, seroma formation, and breast swelling. CONCLUSIONS: Breast cancer
      survivors who received information about BCRL had significantly reduced symptoms
      and increased knowledge about BCRL. In clinical practice, breast cancer survivors
      should be engaged in supportive dialogues so they can be educated about ways to
      reduce their risk of developing BCRL.

PMID- 20140529
TI  - Pathologic response after neoadjuvant therapy is the major determinant of
      survival in patients with esophageal cancer.
AB  - BACKGROUND: Esophageal cancer remains a malignancy with high morbidity and
      mortality despite improvements to diagnosis, staging, chemotherapy, radiation,
      and surgery. Neoadjuvant therapy (NT) may improve oncologic outcome in many
      patients, however the degree to which patients benefit remains unclear. We
      examined the relationship between pathologic response to NT and magnitude of
      benefit in patients with esophageal cancer. METHODS: Using a comprehensive
      esophageal cancer database, we identified patients who underwent esophagectomy
      between 1994 and 2008. Pathologic response was denoted as complete (pCR), partial
      (pPR), and nonresponse (NR). Clinical and pathologic data were compared using
      Fisher's exact and chi-square when appropriate, while Kaplan-Meier estimates were
      used for survival analysis. RESULTS: We identified 347 patients who underwent
      esophagectomy, and 262 (75.5%) were treated with NT. The median age was 66 years
      (28-86 years) with median follow-up of 20 months (1-177 months). There were 106
      (40.5%) patients exhibiting pCR, 95 (36.3%) with pPR, and 61 (23.3%) with NR. The
      rate of R0 resections was higher amongst pCR (100%) compared with 94.7% in pPR (P
      = 0.02) and 87.5% in NR (P = 0.0007). There were 15 (14.2%) recurrences in pCR,
      22 (23.7%) in pPR, and 17 (28.8%) in NR (P = 0.04). Patients achieving pCR had 5
      year disease-free survival (DFS) and overall survival (OS) of 52% and 52%,
      respectively, compared with 36% and 38% in pPR and 22% and 19% in NR (P < 0.0001,
      P < 0.0001). CONCLUSIONS: Esophageal cancer patients frequently succumb to their
      disease. However, patients treated with neoadjuvant therapy who achieve pCR have
      a higher rate of R0 resections, fewer recurrences, and improved 5-year OS and
      DFS.

PMID- 20140531
TI  - Improving breast cancer surgery: a classification and quadrant per quadrant atlas
      for oncoplastic surgery.
AB  - BACKGROUND: Oncoplastic surgery (OPS) has emerged as a new approach for extending
      breast conserving surgery (BCS) possibilities, reducing both mastectomy and re
      excision rates, while avoiding breast deformities. OPS is based upon the
      integration of plastic surgery techniques for immediate reshaping after wide
      excision for breast cancer. A simple guide for choosing the appropriate OPS
      procedure is not available. OBJECTIVE: To develop an Atlas and guideline for
      oncoplastic surgery (OPS) to help in patient selection and choice of optimal
      surgical procedure for breast cancer patients undergoing BCS. METHODS: We
      stratify OPS into two levels based on excision volume and the complexity of the
      reshaping technique. For resections less than 20% of the breast volume (level I
      OPS), a step-by-step approach allows easy reshaping of the breast. For larger
      resections (level II OPS), a mammoplasty technique is required. RESULTS: We
      identified three elements that can be used for patient selection and for
      determination of the appropriate OPS technique: excision volume, tumor location,
      and glandular density. For level II techniques, we defined a quadrant per
      quadrant Atlas that offers a different mammoplasty for each quadrant of the
      breast. CONCLUSIONS: OPS is the "third pathway" between standard BCS and
      mastectomy. The OPS classification and Atlas improves patient selection and
      allows a uniform approach for surgeons. It proposes a specific solution for
      different scenarios and helps improve breast conservation outcomes.

PMID- 20140532
TI  - Identification of medicinal Dendrobium species by phylogenetic analyses using
      matK and rbcL sequences.
AB  - Species identification of five Dendrobium plants was conducted using phylogenetic
      analysis and the validity of the method was verified. Some Dendrobium plants
      (Orchidaceae) have been used as herbal medicines but the difficulty in
      identifying their botanical origin by traditional methods prevented their full
      modern utilization. Based on the emerging field of molecular systematics as a
      powerful classification tool, a phylogenetic analysis was conducted using
      sequences of two plastid genes, the maturase-coding gene (matK) and the large
      subunit of ribulose 1,5-bisphosphate carboxylase-coding gene (rbcL), as DNA
      barcodes for species identification of Dendrobium plants. We investigated five
      medicinal Dendrobium species, Dendrobium fimbriatum, D. moniliforme, D. nobile,
      D. pulchellum, and D. tosaense. The phylogenetic trees constructed from matK data
      successfully distinguished each species from each other. On the other hand, rbcL,
      as a single-locus barcode, offered less species discriminating power than matK,
      possibly due to its being present with little variation. When results using matK
      sequences of D. officinale that was deposited in the DNA database were combined,
      D. officinale and D. tosaense showed a close genetic relationship, which brought
      us closer to resolving the question of their taxonomic identity. Identification
      of the plant source as well as the uniformity of the chemical components is
      critical for the quality control of herbal medicines and it is important that the
      processed materials be validated. The methods presented here could be applied to
      the analysis of processed Dendrobium plants and be a promising tool for the
      identification of botanical origins of crude drugs.

PMID- 20140534
TI  - Management and outcome of gastrointestinal stromal tumors of the duodenum.
AB  - BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are uncommon and
      relatively small subset of GISTs whose optimal surgical procedure has not been
      well defined. We conducted this study to present the surgical experience in our
      institution and to analyze the postoperative outcome of duodenal GISTs. METHODS:
      A retrospective clinicopathologic analysis was performed for nine duodenal GIST
      patients who underwent surgery from May 2001 to April 2009. The median follow-up
      period was 22 months (range: 13-61 months). RESULTS: A total of nine patients
      (six males/three females) with a median age of 52 years (range: 45-73 years) were
      treated. The most common presentation was abdominal pain (45%), and the second
      portion of duodenum (45%) was most common dominant site. All of the patients
      underwent limited resection: there were seven wedge resections with primary
      closures (five open/two laparoscopic) and two segmental resections with end-to
      end duodenojejunostomies. The median tumor size was 3.5 cm (range: 1.9-5.5 cm),
      and the mitotic count was less than fivemitoses/50 high power fields (HPF) in all
      cases. None patients had neoadjuvant or adjuvant therapy. All of the patients
      were alive and disease-free. CONCLUSION: We obtained excellent disease-free
      survival following limited resection with clear margins. Limited resection should
      be considered a treatment option for duodenal GIST.

PMID- 20140533
TI  - Neighborhood socioeconomic environment and sexual network position.
AB  - Rates of sexually transmitted infections (STIs) are strongly associated with
      neighborhood poverty; however, the mechanisms responsible for this association
      remain unclear. Using a population-based study of sexual networks among urban
      African American adolescents, we tested the hypothesis that poverty,
      unemployment, and the sex ratio drive STI rates by affecting sexual network
      structure. Participants were categorized as being in one of three network
      positions that had previously been found to be strongly linked to infection with
      chlamydia and gonorrhea: being in a confirmed dyad (i.e., a monogamous pair),
      being connected to a larger network through one partner, and being in the center
      of a larger network. We found that only poverty was statistically significantly
      associated with sexual network position. Residing in the poorest third of
      neighborhoods was associated with 85% decreased odds of being in confirmed dyads.
      There was no association of sexual network position with neighborhood employment.
      Living in a neighborhood with an unequal number of young men and women appeared
      to be associated with a higher likelihood of being in a confirmed dyad; however,
      the differences were not statistically significant. These results suggest that
      poverty may impact STI rates by shaping sexual network structure, but we did not
      find any evidence that this association operates through unemployment or the sex
      ratio.

PMID- 20140535
TI  - Pterostilbene inhibits pancreatic cancer in vitro.
AB  - INTRODUCTION: Stilbenes are phenolic compounds present in grapes and blueberries.
      Resveratrol, a naturally occurring compound present in grapes, has been shown to
      have potent antioxidant properties as well as an ability to induce apoptosis.
      Resveratrol has also been reported to have significant inhibitory effects against
      a variety of primary tumors including breast, colon, and prostate. Pterostilbene,
      a naturally occurring analogue of resveratrol found in blueberries, also has
      antioxidant and antiproliferative properties. It is also substantially more
      bioavailable orally than resveratrol. These effects have not been studied in
      pancreatic cancer. We hypothesized that pterostilbene would inhibit pancreatic
      cancer cell growth in vitro. MATERIALS AND METHODS: Two pancreatic cancer cell
      lines (MIA PaCa and PANC-1) were cultured using standard techniques. Cells were
      treated with graduated doses of pterostilbene ranging from 10 to 100 microM. Cell
      viability was measured by MTT at 24, 48, and 72 h. RESULTS: Pterostilbene
      decreases cell viability in both cancer cell lines in a concentration- and time
      dependent manner. Higher doses (75-100 microM) caused a significant reduction in
      cell viability at 24 and 48 h. However, by 72 h, all tested concentrations of
      pterostilbene (10 to 100 microM) resulted in significantly reduced cell viability
      in both pancreatic cancer cell lines in a dose-dependent fashion. Pterostilbene
      caused a dose-dependent 10-63% inhibition in MIA PaCa-2 cells and 10-75%
      inhibition in PANC-1 cells. DISCUSSION: Treatment of pancreatic cancer cells in
      vitro with Pterostilbene leads to inhibition of cell proliferation and/or cell
      death, cell cycle arrrest, mitochondrial membrane depolarization, and activation
      of effector caspases. This naturally occurring agent may have a role in treating
      pancreatic cancer. CONCLUSIONS: Pterostilbene inhibits the growth of pancreatic
      cancer in vitro. Further, in vitro mechanistic studies and in vivo experiments
      are warranted to determine its potential for the treatment of pancreatic cancer.

PMID- 20140536
TI  - Influence of body mass index on complications and oncologic outcomes following
      hepatectomy for malignancy.
AB  - BACKGROUND: Following hepatectomy for malignancy, the effect of body mass index
      (BMI) on hepatic and oncologic outcomes is unknown. METHODS: Two hundred seventy
      nine post-hepatectomy patients with malignancy from our center were included in
      the cohort (1996-2006). BMI was categorized using World Health Organization
      criteria. The effect of BMI was evaluated using risk-adjusted Cox models for time
      to recurrence and overall survival. RESULTS: Seventy-nine patients (28.3%) had
      primary hepatobiliary cancers, 134 (48.0%) had colorectal metastases, and 66
      (25.3%) had other metastases. Thirty-five percent of patients were obese (BMI >
      30). Obese patients had more hepatic-specific perioperative complications (27.8%
      vs. 15.9%, p = 0.018), bile leaks (18.6% vs. 9.9%, p = 0.030), post-operative
      pneumonia (9.3% vs. 2.2%, p = 0.0074), intra-abdominal abscesses (7.2% vs. 1.7%,
      p = 0.017), acute renal failure (7.2% vs. 1.7%, p = 0.017), urinary tract
      infections (16.4% vs. 7.7%, p = 0.024), and longer lengths of stay (10.5 vs.8.6
      days, p = 0.029). Obese and non-obese patients had similar perioperative
      mortality, time to recurrence, and overall survival on univariate analysis.
      However, after adjusting for demographic, tumor, and operative characteristics,
      and complications, increasing BMI displayed improved recurrence-free (HR 0.90,
      95% CI 0.86-0.95) and overall survival (HR 0.96, 95% CI 0.92-0.99). CONCLUSIONS:
      High BMI patients may have better oncologic outcomes despite higher perioperative
      morbidity and hepatic complications following hepatectomy. These findings have
      important clinical and biological implications.

PMID- 20140537
TI  - Altered expression of the small guanosine triphosphatase RhoA in human temporal
      lobe epilepsy.
AB  - The small guanosine triphosphatase RhoA has recently been implicated in the
      pathogenesis of epilepsy in animals. In this study, we investigated the
      expression of RhoA in human epilepsy. Brain tissue samples from 40 patients with
      intractable epilepsy and 14 histologically normal temporal lobes from control
      patients were used to compare RhoA immunoreactivity using immunohistochemistry,
      immunofluorescent staining, and western blotting. Immunohistochemical staining
      and western blot analysis showed that RhoA immunoreactivity was increased in the
      patient group (p < 0.05). Immunofluorescent staining showed that RhoA was mainly
      expressed on cell membranes and in the cytoplasm. Our findings demonstrate that
      upregulation of RhoA immunoreactivity occurs in the brains of patients with
      intractable epilepsy.

PMID- 20140538
TI  - Sperm retrieval during critical illness.
AB  - Objective of this study is to review technical methods to retrieve sperm from
      critically ill/injured patients after an appropriate family request, possible
      harmful effects on sperm production/function by ICU medications or concurrent
      illnesses, and ethical considerations for hospitals and care providers in
      providing this resource. Design used for this study includes: literature review,
      PubMed 1998-2009, and authors' files. There are no interventions. In conclusion,
      although successful and unsuccessful pregnancies following sperm removal from
      critically-ill patients are reported, no firm probability predictions for either
      result are known. Acute and chronic diseases that effect the hypothalamic
      pituitary-gonadal axis and multiple medications common to the ICU may reduce
      sperm production or function. Retrieval methods before and after cardio
      respiratory death differ and often require intracytoplasmic sperm injection or
      other in vitro fertilization techniques to achieve a subsequent pregnancy. The
      proactive development of a collaborative policy/procedure to identify appropriate
      roles for the hospital, its employees, and affiliated critical care and urology
      physicians is strongly recommended.

PMID- 20140540
TI  - Acute promyelocytic leukemia in a young patient with breast cancer.

PMID- 20140539
TI  - Changes in brain cholesterol metabolome after excitotoxicity.
AB  - Excitotoxicity due to excess stimulation of glutamate receptors in neurons is
      accompanied by increased Ca(2+) influx, stimulation of Ca(2+)-dependent enzymes,
      ATP depletion, increase in lipid peroxidation products, and loss of glutathione.
      These changes resemble neurochemical alterations in acute neuronal injury
      (stroke, spinal cord injury, and traumatic brain injury) and chronic
      neurodegenerative diseases such as Alzheimer's disease. Intracerebroventricular
      injection of the potent glutamate analog kainate in rats results in increased
      cholesterol concentration in the hippocampus at short to medium time intervals,
      i.e., 3 days-1 week post-injection, as detected by gas chromatography-mass
      spectrometry in the lesioned hippocampus. This is accompanied by an early
      increase in levels of cholesterol biosynthetic precursors and increases in both
      enzymatically derived oxysterols such as 24-hydroxycholesterol and cholesterol
      oxidation products (COPs) generated by reactive oxygen species, including
      cholesterol epoxides and 7-ketocholesterol. In contrast to COPs, no change in
      concentration of the neurosteroid pregnenolone was found after KA injury.
      Cholesterol and COPs significantly increase exocytosis in cultured PC12 cells and
      neurons, and both oxysterols and COPs are able to induce cytotoxic and apoptotic
      injuries in different cell types, including neurons. Together, the findings
      suggest that increased cholesterol and COPs after KA excitotoxicity could
      themselves lead to disturbed neuronal ion homeostasis, increased neurotransmitter
      release, and propagation of excitotoxicity.

PMID- 20140541
TI  - Diagnostic approaches to acute transfusion reactions.
AB  - The erroneous transfusion of ABO-incompatible red cells may lead to life
      threatening hemolysis and complement-induced shock, resulting in death in less
      than 10% of cases (acute hemolytic transfusion reaction, AHTR). Identification of
      the cause of an erroneous transfusion is accomplished in nearly all incidents
      merely by checking the identity of the patient, blood sample and blood bag. The
      erroneous transfusion is confirmed by serological and--in the case of a fatality-
      immunohistochemical methods. The differential diagnosis should rule out
      transfusion-related acute lung injury (TRALI), other immunologically triggered
      causes such as febrile nonhemolytic transfusion reaction (FNHTR) or allergic
      reactions, but also nonimmunological causes such as bacterial contamination of
      the blood components, transfusion-associated circulatory overload (TACO) and
      other rare events such as citrate overload or embolism (by air or debris). In the
      case of a fatality, evaluation of a patient's medical records, serological and
      microbiological analyses, autopsy and histology, taken together, clarify
      questions of causality.

PMID- 20140542
TI  - Implicit attitudes and explicit motivation prospectively predict physical
      activity.
AB  - BACKGROUND: Contemporary approaches to physical activity motivation and promotion
      focus on explicit motivational processes which regulate intentional physical
      activity. Less is known about the role of implicit processes, which may be
      instrumental in regulating habitual aspects of unintentional (i.e., incidental)
      physical activity (PA). PURPOSE: To test the proposition that the routine nature
      of unintentional PA makes it amenable to control by implicit processes. METHODS:
      Participants (N = 201) completed measures of explicit motivation (i.e., efficacy
      beliefs, outcome expectations, behavioral intentions, perceived behavioral
      control) and implicit attitudes toward physical activity, and then wore a
      pedometer for 1 week. RESULTS: Implicit attitudes positively predicted PA after
      controlling for well-established predictors of intentional physical activity.
      CONCLUSIONS: PA motivation involves both explicit and implicit processes, and PA
      promotion efforts may be enhanced by attending to relevant implicit motivation
      processes.

PMID- 20140543
TI  - Frovatriptan in the practice of office-based neurologists/pain therapists:
      Results of postmarketing surveillance study ALADIN.
AB  - INTRODUCTION: Large postmarketing surveillance (PMS) studies have demonstrated
      the efficacy and tolerability of frovatriptan for treatment of acute migraine in
      patients attending general practitioners (GPs). The aim of the ALADIN (Allegro
      Anwendung durch interessierte Neurologen [Allegro application by interested
      neurologists]) PMS study was to evaluate frovatriptan in patients attending
      neurologists or pain therapists. METHODS: Patients fulfilling International
      Headache Society criteria for migraine, with or without aura, were enrolled.
      Patients completed an attack diary, including details of the attack, time to
      onset of action of frovatriptan, and recurrence of headache. Physicians completed
      a case report form detailing prior and actual migraine treatment. Frovatriptan
      2.5 mg was administered for up to three consecutive attacks. RESULTS: In total,
      2160 patients were enrolled and data were obtained for 5831 attacks. Patients
      attending neurologists had more frequent attacks and longer history of migraine
      compared with those attending GPs. Median time to frovatriptan onset of action
      was 40 min and time to freedom from headache 70 min. An average of 1.2
      frovatriptan tablets was required per attack, and mean additional analgesic use
      was 0.13. Recurrent headache occurred in 13.6%-15.5% of patients. Physicians as
      well as patients judged frovatriptan onset and duration of action as at least
      "good" in approximately 80% of attacks. A similar number judged the efficacy of
      frovatriptan against headache as "better" than previous treatment. The study drug
      was generally well tolerated. The frequency of adverse events was 0.6%.
      CONCLUSION: Frovatriptan, with fast onset of action and low rate of headache
      recurrence, was efficacious and well accepted by migraineurs attending
      neurologists or pain therapists. Approximately 80% of patients wished to continue
      migraine treatment with frovatriptan.

PMID- 20140544
TI  - [Neoplastic meningitis. Diagnosis and individualised therapy].
AB  - Neoplastic meningitis is a diffuse dissemination of tumour cells in the
      cerebrospinal fluid (CSF), leptomeninges, or both. It occurs in approximately 5
      10% of malignant diseases, most often in breast cancer, lung cancer, melanoma,
      and B-cell lymphoma. Symptoms of neoplastic meningitis include head or back pain,
      cranial nerve palsies, diffuse radicular symptoms, and psychiatric disturbances.
      Magnetic resonance imaging shows nodular contrast enhancement lining the CSF
      spaces. Positive CSF cytology requires optimal sampling and processing, and the
      treatment of neoplastic meningitis must be individualized. The CSF dissemination
      can be treated with intrathecal chemotherapy with methotrexate or Ara-C.
      Radiotherapy should be applied only to symptomatic solid spinal manifestations or
      fast progressing cranial nerve palsies. Systemic chemotherapy is needed to
      control solid manifestations or, in the case of substances entering the CSF, to
      support intrathecal chemotherapy.

PMID- 20140545
TI  - [DGPPN young physician campaign 4. "Psychiatry and psychotherapy without
      physicians? The current perspective"].

PMID- 20140602
TI  - Double-bundle ACL reconstruction: how big is the learning curve?
AB  - The study aim was to determine whether an experienced ACL surgeon could convert
      from a single-bundle to a double-bundle technique with relative accuracy. We also
      wanted to determine whether there was a significant learning curve. Ten double
      bundle ACL reconstruction procedures were carried out on suitable individuals.
      Following the procedure, all patients underwent a CT scan of the relevant knee.
      Femoral and tibial tunnel locations were then measured and compared to reference
      anatomical locations previously described in the literature. The results were not
      known to the surgeon until all 10 cases were completed. The total percentage
      difference between the sum of all four study tunnel locations from their
      reference anatomical positions was calculated for each patient to assess overall
      accuracy in tunnel placement. Surgical time and all complications were recorded.
      There were no complications. The surgical time for patient 1 was 125 min and 65
      min for patient 10. There was a tendency to place the anteromedial tunnel on the
      femur more distal than its anatomical location. The femoral posterolateral tunnel
      position was placed distal to its anatomical location in all cases. As a
      consequence, it was also slightly anterior compared to its anatomical location.
      Accurate tibial tunnel placement was achieved for both the AM and the PL tunnels.
      An improvement in tunnel placement was observed over the 10 cases. This present
      study shows that it is possible for an experienced ACL surgeon to convert from a
      transtibial single-bundle technique to a medial portal double-bundle
      reconstruction with relative accuracy.

PMID- 20140603
TI  - BDNF plasma levels decrease during benzodiazepine withdrawal in patients
      suffering from comorbidity of depressive disorder and benzodiazepine dependence.

PMID- 20140604
TI  - Fetoscopic fetal transesophageal electrocardiography: a minimally invasive tool
      for cardiac monitoring, diagnostics, and intervention in human fetuses.
AB  - Therapy-refractory supraventricular tachycardias commonly result in hydrops and
      death in human fetuses. Fetal transesophageal electrocardiography may aid in
      understanding its underlying electrophysiological mechanism and allow
      stimulation. Percutaneous fetoscopic deployment of an electrode catheter into the
      fetal esophagus by way of a single trocar was performed in a human fetus and
      permitted the recording of a fetal transesophageal electrocardiogram at 35 + 6
      weeks of gestation. Fetal transesophageal electrocardiography can be achieved in
      human fetuses by way of a minimally invasive percutaneous fetoscopic approach and
      carries the potential to improve diagnosis and management of therapy-refractory
      supraventricular tachycardias in human fetuses.

PMID- 20140605
TI  - Complete heart block and echocardiographic abnormalities caused by pyrotechnic
      chest trauma.

PMID- 20140606
TI  - Effect of cibenzoline on biventricular pressure gradients in a pediatric patient
      with hypertrophic obstructive cardiomyopathy.
AB  - This report presents the case of an 8-year-old male with biventricular
      hypertrophic obstructive cardiomyopathy who achieved a successful reduction of
      the pressure gradients by treatment with cibenzoline. Ultrasound echocardiography
      showed marked intraventricular septal hypertrophy and left midventricular and
      right ventricular outflow obstructions. A cardiac catheterization revealed left
      midventricular and right outflow obstructions associated with pressure gradients
      of 100 and 35 mmHg, respectively. An intravenous injection of 28 mg (1.4 mg/kg)
      cibenzoline immediately improved the biventricular pressure gradients. Therefore,
      oral cibenzoline treatment was initiated, the dose was increased to 150 mg/day,
      and both pressure gradients remained low, without any complications at the time
      of discharge, 4 months later.

PMID- 20140607
TI  - Malignant coronary artery anomaly in a survivor of Hodgkin's lymphoma.

PMID- 20140608
TI  - Magnetic resonance imaging-aided diagnosis of an inferior sinus venosus defect: a
      case report.

PMID- 20140609
TI  - MicroRNAs in cardiac development.
AB  - The transcriptional regulation of cardiovascular development requires precise
      spatiotemporal control of gene expression, and heterozygous mutations of
      transcription factors have frequently been implicated in human cardiovascular
      malformations. A novel mechanism involving post-transcriptional regulation by
      small, noncoding microRNAs (miRNAs) has emerged as a central regulator of many
      cardiogenic processes. We are beginning to understand the functions that miRNAs
      play during essential biologic processes, such as cell proliferation,
      differentiation, apoptosis, stress response, and tumorigenesis. The
      identification of miRNAs expressed in specific cardiac and vascular cell types
      has led to the discovery of important regulatory roles for these small RNAs
      during cardiomyocyte differentiation, cell cycle, conduction, and vessel
      formation. Here, we overview the recent findings on miRNA regulation in
      cardiovascular development. Further analysis of miRNA function during
      cardiovascular development will allow us to determine the potential for novel
      miRNA-based therapeutic strategies.

PMID- 20140610
TI  - Occurrence and persistence of erythromycin resistance genes (erm) and
      tetracycline resistance genes (tet) in waste treatment systems on swine farms.
AB  - Animal manure from modern animal agriculture constitutes the single largest
      source of antibiotic resistance (AR) owing to the use of large quantities of
      antibiotics. After animal manure enters the environment, the AR disseminates into
      the environment and can pose a potentially serious threat to the health and well
      being of both humans and animals. In this study, we evaluated the efficiency of
      three different on-farm waste treatment systems in reducing AR. Three classes of
      erythromycin resistance genes (erm) genes (B, F, and X) conferring resistances to
      macrolide-lincosamides-streptogramin B (MLS(B)) and one class of tetracycline
      resistance genes (tet) gene (G) conferring resistance to tetracyclines were used
      as models. Real-time polymerase chain reaction assays were used to determine the
      reservoir sizes of these AR genes present in the entire microbiome. These classes
      of AR genes varied considerably in abundance, with erm(B) being more predominant
      than erm(F), erm(X), and tet(G). These AR genes also varied in persistence in
      different waste treatment systems. Aerobic biofiltration reduced erm(X) more
      effectively than other AR genes, while mesophilic anaerobic digestion and lagoon
      storage did not appreciably reduce any of these AR genes. Unlike chemical
      pollutants, some AR genes could increase after reduction in a preceding stage of
      the treatment processes. Season might also affect the persistence of AR. These
      results indicate that AR arising from swine-feeding operations can survive
      typical swine waste treatment processes and thus treatments that are more
      effective in destructing AR on farms are required.

PMID- 20140611
TI  - Risk stratification of solitary pulmonary nodules by means of PET using (18)F
      fluorodeoxyglucose and SUV quantification.
AB  - PURPOSE: (18)F-fluorodeoxyglucose (FDG) PET is the most accurate imaging modality
      in characterizing a solitary pulmonary nodule (SPN). Besides visual image
      interpretation, semiquantitative analysis using standardized uptake values (SUV)
      is performed to improve diagnostic accuracy. Mostly, an SUV threshold of 2.5 is
      applied to differentiate between benign and malignant lesions. In this study we
      analysed the use different SUV thresholds to predict the post-test probability of
      malignancy for the individual patient considering his pre-test probability.
      Furthermore, we investigated the prognostic value of SUV in SPN for survival.
      METHODS: This retrospective study included 140 consecutive patients who underwent
      FDG PET for evaluation of SPN. Visual interpretation was performed by two
      readers. For semiquantitative analysis, maximum SUV (SUV(max)) was measured in
      all SPN. A final diagnosis was obtained by pathological examination or follow-up
      of more than 2 years. In a nomogram, positive and negative predictive values (PPV
      and NPV) were plotted against the hypothetical SUV threshold to determine the
      optimum SUV threshold. Survival was analysed using the Kaplan-Meier method and
      log-rank test. RESULTS: The prevalence of malignancy was 57%. The FDG uptake in
      malignant SPNs was higher than in benign SPNs (SUV 9.7 +/- 5.5 vs 2.6 +/- 2.5, p
      < 0.01). More than 90% of SPNs with an SUV below 2.0 were benign (sensitivity,
      specificity, NPV of 96, 55 and 92%). The highest diagnostic accuracy was achieved
      with an SUV of 4.0 (sensitivity, specificity and accuracy of 85%). Visual
      interpretation achieved corresponding values of 94, 70 and 84%, respectively. In
      lung cancer higher FDG uptake (SUV(max) >or= 9.5) was associated with shorter
      survival (median survival 20 months) and low FDG uptake with longer survival (>75
      months). CONCLUSION: FDG PET allows assessment of the individual risk for
      malignancy in SPNs by considering tumoural SUV and pre-test probability. Higher
      FDG uptake in lung cancer as measured by SUV analysis is a prognostic factor. In
      patients with low FDG uptake in an SPN and increased risk during surgery omission
      of diagnostic thoracotomy may be warranted.

PMID- 20140612
TI  - Assessment of the Na/I symporter as a reporter gene to visualize oncolytic
      adenovirus propagation in peritoneal tumours.
AB  - PURPOSE: In vivo imaging of the spread of oncolytic viruses using the Na/I
      symporter (NIS) has been proposed. Here, we assessed whether the presence of NIS
      in the viral genome affects the therapeutic efficacy of the oncolytic adenovirus
      dl922-947 following intraperitoneal administration, in a mouse model of
      peritoneal ovarian carcinoma. METHODS: We generated AdAM7, a dl922-947 oncolytic
      adenovirus encoding the NIS coding sequence. Iodide uptake, NIS expression,
      infectivity and cell-killing activity of AdAM7, as well as that of relevant
      controls, were determined in vitro. In vivo, the propagation of this virus in the
      peritoneal cavity of tumour-bearing mice was determined using SPECT/CT imaging
      and its therapeutic efficacy was evaluated. RESULTS: In vitro infection of
      ovarian carcinoma IGROV-1 cells with ADAM7 led to functional expression of NIS.
      However, the insertion of NIS into the viral genome resulted in a loss of
      efficacy of the virus in terms of replication and cytotoxicity. In vivo, on
      SPECT/CT imaging AdAM7 was only detectable in the peritoneal cavity of animals
      bearing peritoneal ovarian tumours for up to 5 days after intraperitoneal
      administration. Therapeutic experiments in vivo demonstrated that AdAM7 is as
      potent as its NIS-negative counterpart. CONCLUSION: This study demonstrated that
      despite the detrimental effect observed in vitro, insertion of the reporter gene
      NIS in an oncolytic adenovirus did not affect its therapeutic efficacy in vivo.
      We conclude that NIS is a highly relevant reporter gene to monitor the fate of
      oncolytic adenovectors in live subjects.

PMID- 20140613
TI  - Integrating imaging modalities: what makes sense from a workflow perspective?
AB  - PURPOSE: From a workflow/cost perspective integrated imaging is not an obvious
      solution. An analysis of scanning costs as a function of system cost and relevant
      imaging times is presented. This analysis ignores potential clinical advantages
      of integrated imaging. METHODS: An analysis comparing separate vs integrated
      imaging costs was performed by deriving pertinent equations and using reasonable
      cost numbers for imaging devices and systems, room and other variable costs.
      Integrated systems were divided into those sequentially and simultaneously.
      Sequential scanning can be done with two devices placed in a single or in two
      different scanning rooms. Graphs were derived which represent the cost difference
      between integrated imaging system options and their separate counterparts vs
      scanning time on one of the devices and cost ratio of an integrated system and
      its counterpart of separate devices. RESULTS: Integrated systems are favoured by
      the fact that patients have to be up- and downloaded only once. If imaging times
      become longer than patient changing times, imaging on separate devices is
      advantageous. An integrated imaging cost advantage is achieved if the integrated
      systems typically and overall cost three fourths or less of the separate systems.
      If PET imaging takes 15 min or less, PET/CT imaging costs less than separate PET
      and CT imaging, while this time is below 5 min for SPECT/CT. A two-room
      integrated system has the added advantage that patient download time is not cost
      relevant, when imaging times on the two devices differ by more than the patient
      download time. CONCLUSION: PET/CT scanning is a cost-effective implementation of
      an integrated system unlike most current SPECT/CT systems. Integration of two
      devices in two rooms by a shuttle seems the way how to make PET/MR cost-effective
      and may well also be a design option for SPECT/CT systems.

PMID- 20140614
TI  - Molecular imaging of vascular inflammation.

PMID- 20140616
TI  - Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose
      rate, in combination with cisplatin in patients with advanced non-small-cell lung
      cancer.
AB  - INTRODUCTION: Although some studies have suggested that gemcitabine delivered as
      a fixed dose rate (FDR) infusion of 10 mg/m(2)/min could be more effective than
      when administered as the standard 30-min infusion, the available pharmacokinetic
      data are still too limited to draw definitive conclusions. This study is aimed to
      investigate the plasmatic and intracellular pharmacokinetics of gemcitabine given
      as FDR at doses of 600 and 1,200 mg/m(2) in combination with 75 mg/m(2) of
      cisplatin in advanced non-small-cell lung cancer (NSCLC) patients. PATIENTS AND
      METHOD: The patients were divided into two groups receiving different initial
      doses of the drug: 4 patients received 600 mg/m(2) gemcitabine 60-min i.v.
      infusion and 4 patients 1,200 mg/m(2) gemcitabine 120-min i.v. infusion both as a
      FDR of 10 mg/m(2)/min on days 1 and 8 of a 21-day cycle (at first cycle). At the
      second cycle, all patients were treated with gemcitabine at 1,200 mg/m(2) 120-min
      i.v. infusion (FDR of 10 mg/m(2)/min) on days 1 and 8 of a 21-day cycle. At each
      cycle, gemcitabine was administered alone on day one, and in combination with 75
      mg/m(2) of cisplatin on day 8. Plasmatic and intracellular pharmacokinetic
      analyses were performed on blood samples collected at defined time points before,
      during and after gemcitabine infusion. RESULTS: The plasmatic pharmacokinetic
      parameters were clearly different when the patients received a higher gemcitabine
      dose in the second cycle compared to the lower dose of the first course; in the
      same time, the intracellular drug levels were not modified. Comparing the
      pharmacokinetic parameters of different patients treated at different dose
      levels, the results appeared to be quite similar. CONCLUSIONS: A substantially
      higher accumulation of metabolites in peripheral blood mononuclear cells was
      observed when the longer infusion time was employed, suggesting a pharmacological
      advantage for this treatment schedule.

PMID- 20140618
TI  - [Correction of corneal astigmatism with toric lenses : Theory and clinical
      aspects].
AB  - In the last decades, the implantation of pseudophakic and phakic toric lenses has
      become widespread for correcting corneal astigmatism: in cataract surgery cases
      with implantation of a posterior chamber lens and in refractive surgery cases
      with implantation of phakic lenses. The purpose of this educational and training
      article is to familiarize the reader with the application of pseudophakic and
      phakic toric lenses, to show which parameters are necessary for calculating toric
      lenses, to present a matrix-based calculation scheme for pseudophakic and phakic
      toric lenses, to explicitly demonstrate the step-by-step calculations with
      clinical examples, and to show the impact of lens dislocation (especially
      rotation) on refractive outcome.

PMID- 20140619
TI  - Prospective randomized trial comparing short-term antibiotic therapy versus
      standard therapy for acute uncomplicated sigmoid diverticulitis.
AB  - PURPOSE: To date, the standard therapy used for acute episodes of uncomplicated
      sigmoid diverticulitis has been a 7-10-day antibiotic treatment regimen. Thanks
      to the development of highly potent, broad-spectrum antibiotics such as
      ertapenem, the question arises as to whether the duration of treatment of acute
      uncomplicated sigmoid diverticulitis can be reduced by using highly effective
      antibiotics. METHODS: To compare the efficacy of short-term therapy (4 days)
      versus standard therapy (7 days) for uncomplicated sigmoid diverticulitis, a
      prospective randomized multicenter trial was conducted. Patients were randomized
      to treatment groups after 4 days. Both patient groups were monitored until
      discharge and were followed up after 4-6 weeks and 52 weeks. [corrected] The
      results were standardized and statistically evaluated. RESULTS: Between 16
      December 2004 and 15 November 2007, 123 patients from 11 hospitals were enrolled
      in the study. Seventeen patients dropped out. In the remaining 106 cases, no
      significant differences were discerned between the two groups in terms of the
      basic data, apart from the mean number of diverticulitis episodes (short term
      1.28 +/- 0.64 versus standard 1.64 +/- 1.07, p = 0.037). The mean hospital stay
      was 8.8 days, with significant differences seen between short-term and standard
      therapy (7.8 +/- 2.8 versus 9.7 +/- 3.2 days; p = 0.002). After 4 days, treatment
      was classified as having proved successful in 98.0% of cases and after 7 days in
      98.2% of cases. An overall success rate of 95.1% (94.0% versus 96.2%, n.s.) was
      recorded after 1 month. CONCLUSION: The results obtained with short-term
      ertapenem therapy (4 days) showed that this was as effective as standard therapy
      (7 days) for treatment of uncomplicated sigmoid diverticulitis.

PMID- 20140620
TI  - Subcutaneous Redon drains do not reduce the incidence of surgical site infections
      after laparotomy. A randomized controlled trial on 200 patients.
AB  - PURPOSE: Surgical site infections (SSI) cause excess morbidity and mortality in
      modern surgery. Several different approaches to reduce the incidence of SSI have
      been investigated with variable results. METHOD: This is to our knowledge the
      first systematic randomized evaluation in patients undergoing laparotomy in
      visceral surgery to clarify whether widely used subcutaneous drains (Redon)
      affect wound infection as the primary outcome measure. RESULTS: In 200 patients,
      we were unable to show a statistically significant impact on the postoperative
      healing process in patients with the full variety of abdominal surgical
      interventions. Overall, we observed surgical site infection in 9.5% of all
      patients (n = 19), of these n = 9 (47.4%) were in the control group without a
      drain, and 10 (52.6%) were in the experimental group with a Redon drain (not
      significant). CONCLUSION: As this study could not demonstrate a reduction of SSI
      by the use of Redon drains, there is no indication for prophylactic subcutaneous
      suction drains after laparotomy.

PMID- 20140617
TI  - Bendamustine pharmacokinetic profile and exposure-response relationships in
      patients with indolent non-Hodgkin's lymphoma.
AB  - PURPOSE: The pharmacokinetic profiles of bendamustine and active metabolites were
      defined in patients with rituximab-refractory, relapsed indolent B-cell non
      Hodgkin's lymphoma, and supported understanding of exposure-response
      relationships for efficacy and safety. METHODS: Bendamustine was administered as
      a 60-min 120 mg/m(2) intravenous infusion on days 1 and 2 of six 21-day cycles.
      Pharmacokinetic models were developed, with covariate assessment. Correlations
      between bendamustine exposure and responder status or occurrence of neutropenia,
      thrombocytopenia, fatigue, nausea, and vomiting were examined. RESULTS: Following
      a single dose of bendamustine HCl, concentrations declined in a triphasic manner,
      with rapid distribution, intermediate, and slow terminal phases. The intermediate
      t (1/2) (40 min) was considered the pharmacologically relevant (beta elimination)
      t (1/2) since the initial phases accounted for 99% of the AUC. Age, sex,
      mild/moderate renal, or mild liver impairment did not alter pharmacokinetics.
      Metabolite concentrations were low relative to parent. No correlation was
      observed between exposure and safety or efficacy measures because of the limited
      range of exposures after 120 mg/m(2) administration, except bendamustine C (max)
      was a significant (P value = 0.013) predictor of the probability of nausea in
      patients, most of whom were pretreated with antiemetics. CONCLUSIONS: The BSA
      based dosing regimen for bendamustine achieved the targeted exposure and was
      associated with a high incidence of therapeutic response. Given the short t (1/2)
      and low concentrations of bendamustine observed by 12 h after dosing, the single
      dose profile for bendamustine described by these analyses is expected to be
      representative of the multiple-dose profile. The occurrence of nausea was
      significantly related to bendamustine exposure, with the probability of nausea
      increasing as bendamustine C (max) increases.

PMID- 20140621
TI  - Design and finite-element evaluation of a versatile assembled lumbar interbody
      fusion cage.
AB  - INTRODUCTION: When an interbody cage is inserted into a human being's lumbar
      spine, not only the design, but also the material used is considerably crucial,
      particularly when minimally invasive lumbar fusion (MILIF) approaches are
      considered. The purpose of this study was to design a multi-function cage (either
      for MILIF or open lumbar interbody fusion) and also to evaluate the strength of
      the design based on a finite-element model analysis. METHOD: Three-dimensional
      finite-element models that were instrumental in the reproduction of post
      operative conditions under which different cages, such as assembled lumbar
      interbody fusion cages (ALIFC) and the separated ones, could be examined and
      traced after implantation were developed. Simulations were run to realize various
      loading conditions including axial compression, flexion, extension, lateral
      bending and rotation under a constant compressive preload. Meanwhile, the
      evaluation results derived from FEMs data focused on endplate stress
      distribution, peak stress of von Mises and stress of cage. Stress distributions
      on the bone surface were evaluated and discussed as well. RESULTS: The
      consequences of cage insertion, high strains and stresses, were concentrated in
      the areas where the cage and endplate were in contact with each other.
      Simultaneously, contact stresses around the implants seemed to be concentrated
      around the periphery of the device. After implantation of ALIFC, the stiffness of
      the new cages was similar to that of traditional cages in an assemble condition,
      according to the biomechanical data dealing with FEM. Once a separated cage was
      in the place of an assembled cage, the stresses would get symmetrically
      distributed in the lateral areas of the endplate and decrease significantly at
      the center where the separated cage was not in contact with the endplate. The
      stress of the cage was going to be high once being rotating; most significant
      difference of stresses distribution due to the alternative choice has been found
      in the state of rotation. On comparison of peak von Mises stresses on the
      endplates in the new cage, the stresses were symmetrically distributed in the
      lateral areas of the endplate when a separated cage was used in place of an
      assembled cage. CONCLUSION: The new cage was more advantages with regard to
      endplate stress distribution, peak stress of von Mises and stress of cage than
      the assembled state. ALIFC can provide sufficient primary stability for lumbar
      intervertebral fusion and the new cage may be regarded as a suitable device for
      load-bearing implantation.

PMID- 20140622
TI  - Limbal relaxing incision during cataract extraction versus photoastigmatic
      keratectomy after cataract extraction in controlling pre-existing corneal
      astigmatism.
AB  - BACKGROUND: The techniques of limbal relaxing incision (LRI) and photoastigmatic
      keratectomy (PAK) are both effective methods for correcting pre-existing
      astigmatism with cataract extraction, but no previous study has directly compared
      them. PURPOSE: To compare the effects of limbal relaxing incision (LRI) and
      photoastigmatic keratectomy (PAK) on preoperative astigmatism and higher-order
      aberrations (HOAs) in eyes undergoing cataract surgery. SETTING: Kitasato
      University Hospital, Japan. PATIENTS AND METHODS: A retrospective study of eyes
      which had undergone phacoemulsification and intraocular lens implantation through
      an astigmatically neutral incision either accompanied by LRI (LRI group, 20 eyes)
      or followed after 3 months by PAK (PAK group, 27 eyes), to control pre-existing
      corneal astigmatism. RESULTS: Among eyes that underwent LRI, manifest astigmatism
      (corrected to the corneal plane) averaged -1.72 +/- 0.95 D preoperatively and 
      0.98 +/- 0.58 D postoperatively. Corneal astigmatism averaged 2.03 +/- 0.49 D
      preoperatively and 1.34 +/- 0.60 D postoperatively. Among eyes that underwent
      PAK, manifest astigmatism averaged -2.02 +/- 0.64 D preoperatively and -0.70 +/-
      0.58 D postoperatively. Corneal astigmatism averaged 2.30 +/- 0.81 D
      preoperatively and 1.05 +/- 0.36 D postoperatively. With regard to HOAs, in the
      LRI group, corneal HOAs averaged 0.172 +/- 0.051 microm (total aberrations for 4
      mm pupil diameter) and 0.681 +/- 0.433 microm (total, 6 mm) preoperatively, but
      0.172 +/- 0.053 microm (total, 4 mm) and 0.651 +/- 0.187 microm (total, 6 mm)
      postoperatively. In the PAK group, the corneal HOAs averaged 0.179 +/- 0.073
      microm (total, 4 mm) and 0.679 +/- 0.314 microm (total, 6 mm) preoperatively, but
      0.206 +/- 0.095 microm (total, 4 mm) and 0.816 +/- 0.380 microm (6 mm, total)
      postoperatively. The only statistically significant differences in the
      postoperative HOAs between LRI and PAK groups were in the S4 and S6 (spherical
      and spherical-like aberrations being bigger in the PAK group ).There were no
      vision-threatening complications in either group. CONCLUSIONS: PAK is more
      effective than LRI in the control of pre-existing manifest astigmatism. LRI
      causes less accentuation of the spherical HOAs than PAK.

PMID- 20140623
TI  - Colorectal cancer and adenomas are rare in individuals of Turkish descent living
      in the Zaanstreek region in the Netherlands.
AB  - BACKGROUND: Colorectal cancer is one of the most common malignancies in the
      Western world. Screening and detection of its precursor lesion, the adenoma could
      prevent development of colorectal cancer. Many studies have been done to evaluate
      the prevalence of colorectal cancer in different countries. In daily practice, it
      was noticed that colorectal cancer was rarely seen in patients of Turkish decent.
      AIM: To evaluate the prevalence of colorectal cancer and adenoma in patients
      living in the Zaanstreek region, the Netherlands, and correlate these findings
      with ethnicity. MATERIALS AND METHODS: All patients undergoing endoscopy of the
      colon and rectum during a period of 16 consecutive years in whom colorectal
      cancer and/or a polyp were diagnosed, were included in this study. All available
      histological data were retrieved in order to confirm the endoscopic diagnosis.
      RESULTS: In the study period, 907 patients were diagnosed with colorectal cancer.
      Of these 13 (1.4%) were of Turkish descent (10 men and 3 women). The remaining
      894 were authentic Dutch (473 men and 421 women). A total of 2,744 patients had
      one or more polyp(s) during endoscopy. There were 2,705 authentic Dutch (1,386
      men, 1,319 women) and 39 Turkish patients (25 men, 14 women). There was no
      significant difference in gender in either of the groups. CONCLUSION: Colorectal
      cancer and colonic adenoma are rare in patients of Turkish descent living in the
      Zaanstreek region, the Netherlands.

PMID- 20140625
TI  - Single-nucleotide polymorphisms in BER and HRR genes, XRCC1 haplotypes and breast
      cancer risk in Caucasian women.
AB  - PURPOSE: This study aimed to assess whether haplotypes in XRCC1 and SNPs in OGG1
      and XRCC3 were associated with an increased risk of developing breast cancer (BC)
      and early adverse reactions after radiotherapy. METHODS: 43 Italian breast cancer
      patients and 31 healthy controls were genotyped for XRCC1(-77T-->C,194,399), OGG1
      326 and XRCC3-241 by RFLP-PCR. RESULTS: XRCC1-77T-->C, XRCC1-194, OGG1 and XRCC3
      were not associated with BC. On the contrary, we found a significant association
      (p <or= 0.05) between breast cancer occurrence and XRCC1-399. The haplotype (H3)
      containing the variant allele at codon 399, together with variant C allele in the
      promoter and wild-type G allele at codon 194 was associated with higher BC risk
      [p = 0.009, OR = 7.04(1.63-30)]. The probability for developing this tumor was
      also increased by the number of SNPs in different genes. We found a significantly
      higher BC risk in subjects with >or=3 SNPs [OR = 2.72 (0.99-7.39), p = 0.04].
      CONCLUSION: In our study, the 399-Gln allele of XRCC1 increased significantly the
      risk of BC and it may act as a dominant allele [Arg/Arg vs. (Gln/Gln + Arg/Gln),
      OR = 4.67 (95% CI 1.65-13.23), p = 0.005]. The combination of variant alleles at
      codon 399 and in position -77 could affect XRCC1 protein activity, impairing
      genome integrity and promoting cancer occurrence. Also, the number of SNPs in
      several genes involved in BER and HRR mechanisms made higher the risk of sporadic
      BC. We can conclude that genetic variants in multiple repair pathways may have a
      joint or additive effect in cancer risk.

PMID- 20140624
TI  - Effect of type 1 insulin-like growth factor receptor targeted therapy on
      chemotherapy in human cancer and the mechanisms involved.
AB  - INTRODUCTION: Chemotherapy is administered only to patients with advanced
      cancers, typically to modest avail. Hence, the search for innovative approaches
      to treat cancer is growing rapidly. One such approach involves targeting
      molecular pathways identified as encouraging tumor growth and maintenance,
      particularly the type 1 insulin-like growth factor (IGF-1) and its receptor (IGF
      1R) pathway that is important in conferring chemoresistance. MATERIALS AND
      METHODS: This study focuses on IGF-1R targeted therapy, which will enhance
      chemotherapy efficacy, through reviewing recent literature from PubMed and
      Medline databases. CONCLUSION: This review examines data and strategies
      addressing an approach conquering chemoresistance through the combination of IGF
      1R targeted therapy and chemotherapy in cancer patients, as well as the
      mechanisms by which IGF-1R acts as a target. This will impact on future research
      on treatment selection, thereby improving patient prognosis.

PMID- 20140626
TI  - Prognostic and metastatic value of phosphatase of regenerating liver-3 in
      invasive breast cancer.
AB  - PURPOSE: The aim of this study was to investigate the expression of the PRL-3 in
      human invasive breast cancer and to evaluate its clinical and prognostic
      significance. Its potential role in the invasive-metastatic properties of
      invasive breast cancer was also investigated. METHODS: Protein expression of PRL
      3 was evaluated by immunohistochemistry for a consecutive series of 82 invasive
      human breast cancer tissues and 63 matched lymph node metastases, including PRL-3
      mRNA expression analyzed by reverse transcriptase-polymerase chain reaction (RT
      PCR) in malignant, nonmalignant breast tissue samples and lymph node metastases.
      We investigated the correlation of PRL-3 with clinicopathologic features, Overall
      and recurrence-free survival distribution curves were assessed using the Kaplan
      Meier test and log-rank statistics, followed by Cox proportional hazards
      regression model. RESULTS: We found that 70.7% patients expressed a high level of
      PRL-3 protein in their tumors, and its over expression was positive correlated
      with lymph node metastasis (LNM) (P = 0.011). Moreover, The PRL-3 mRNA expression
      was significantly higher in malignant compared to benign breast tissue, while
      increased expression of PRL-3 mRNA was significantly associated with LNM (P =
      0.002). Univariate analysis showed that the positive expression of PRL-3 was a
      poor risk prognostic factor (OS, P = 0.045; RFS, P = 0.034). Multivariate
      analysis using the Cox regression model indicated that high PRL-3 expression was
      an independent unfavorable prognostic factor for RFS. CONCLUSIONS: These results
      strongly suggest that PRL-3 expression can indicate the potential role of LNM to
      some extent. Increasing the risk of tumor metastasis (OR = 3.889). Our results
      also imply that PRL-3 might be a novel molecular marker for predicting relapse of
      invasive breast cancer.

PMID- 20140627
TI  - Potential roles for PA28beta in gastric adenocarcinoma development and diagnosis.
AB  - PURPOSE: This study aimed to investigate the expression level of human proteasome
      activator PA28beta subunit (PA28beta) in gastric adenocarcinomas (GA) tissues and
      investigate its potential role in GA carcinogenesis. METHODS: To investigate the
      expression profile of PA28beta in patients with GA, we employed
      immunohistochemistry for detection of 287 cases of paired GA and adjacent non
      neoplastic tissues. To evaluate the role of PA28beta in GA cells, we measured
      cell growth, colony formation, soft agar, and nude mice tumorigenicity assays in
      MKN-45 GA cells pre- and post-PA28beta transfection. RESULTS: PA28beta had lower
      expression in 183 of 287 GA cases compared to paired normal samples (63.76%; P <
      or = 0.001). Decreased expression was dependent on histological type, TNM stage,
      and differentiation grade. Significantly decreased expression was correlated with
      a diffuse histological type (88/116, 75.86%) compared to an intestinal type
      (84/152, 55.26%; P < or = 0.001), with advanced TNM stages (T3: 44/59, 74.58%;
      T4:25/32, 78.13%) compared to earlier stages (T1: 25/47, 53.19%; T2: 90/149,
      60.40%; P = 0.004), and poorer differentiation grade (poor: 68/90, 75.56%)
      compared to a higher grade (high: 9/18, 50%, moderate: 74/134, 55.22%) (P =
      0.006). Over-expression of PA28beta inhibited cell growth, proliferation, and
      tumorigenicity of MKN-45 GA cells. CONCLUSIONS: These results indicated that
      PA28beta might participate in the origin and progression of GA cancer through
      changes to cell proliferation activity and tumorigenicity. Therefore, PA28beta
      might be a novel biomarker for GA.

PMID- 20140629
TI  - Model for understanding thermal hysteresis during heat stress: a matter of
      direction.
AB  - Thermal hysteresis may be used to quantify and characterize the amount of heat
      stress an animal experiences. Heat stress studies of farm animals suggest that
      above a certain threshold body temperature (Tb) is driven by ambient temperature
      (Ta). Patterns in the Tb-Ta phase diagram indicate the presence of hysteresis.
      When hysteresis is present, there are two values for Tb depending on whether Ta
      is increasing or decreasing. A theoretical delay-relay model is proposed to
      illustrate the hysteretic dynamics of the Tb-Ta relationship when Ta is cyclic.
      Two types of hysteresis, transitional and thermal, are identified. Thermal
      hysteresis becomes prominent when Ta forces Tb into an elliptical limit cycle.
      The area of the ellipse is an indication of the animal's heat load. Also, the
      resulting Tb-Ta pattern depends on the delay (or lag) between Tb and Ta. The
      delay suggests possible levels of heat stress. A greater delay between Tb and Ta
      indicates more time is needed to dissipate the heat load, implying the animal is
      suffering more heat stress. For a given Ta, the Tb on the decreasing (recovery)
      path is always higher than the Tb on the increasing (challenge) path.
      Essentially, the animal requires more energy to dissipate heat than to absorb it.

PMID- 20140628
TI  - Gastrin-releasing peptide links stressor to cancer progression.
AB  - INTRODUCTION: Gastrin-releasing peptide (GRP) plays an important role in cancer
      growth and metastasis; however, the mechanisms of how GRP affects cancer
      progression are not well understood. Recent studies revealed that chronic stress
      is a major risk factor for cancer progression, and this effect may be mediated by
      GRP. In this review, we will discuss the mechanisms and implications of GRP
      linking stressor to cancer progression. MATERIALS AND METHODS: We retrieved the
      studies of the relationship between GRP, stress and cancers through PubMed using
      systematic methods to search, select, and evaluate the findings. RESULTS: The
      results suggested that GRP can mediate the effects of stress on cancers at
      systemic, tissue and cellular levels: Stress elicits the secretion of GRP in the
      brain and GRP in turn activates the stress response pathways resulting in an
      elevation of stress hormones and GRP in the plasma and tissues. GRP in synergy
      with stress hormones stimulates the growth and invasion of cancer cells by
      suppressing the anti-tumor immune function and directly activating the pro
      proliferative and pro-migratory signaling pathways in cancer cells. CONCLUSION:
      GRP is a multi-functional peptide, which acts as a stress mediator as well as a
      growth factor linking stressor to cancer progression. GRP and its high-affinity
      receptor are useful targets for the diagnosis and treatment of cancers.

PMID- 20140630
TI  - Pituitary apoplexy: an overview of 186 cases published during the last century.
AB  - BACKGROUND: Pituitary apoplexy is a rare and life-threatening complication
      occurring in 0.6-10.5% of all cases of pituitary adenomas. Although the
      association between pituitary apoplexy and visual dysfunction has been recognized
      for a long time, the optimal management of this problem still remains
      controversial. The purpose of this overview was to present the surgical
      experience by analyzing the literature on the management of pituitary apoplexy
      for better treatment of these cases. MATERIALS AND METHOD: To establish a new
      guideline for the surgical treatment of this entity, publications reported during
      the last century and databases containing medical literature were analyzed. In
      addition, an illustrative case with pituitary apoplexy presenting with complaints
      of sudden onset severe headache associated with nausea, vomiting, and a sudden
      loss of vision was described. In fact, the experience in our complicated patient
      prompted us to review the available literature on the management of pituitary
      apoplexy to date. CONCLUSIONS: Based on an overview of 186 cases of apoplectic
      pituitary adenoma presenting with monocular or binocular blindness, we highlight
      the importance of correct diagnosis and an early, but not necessarily emergency,
      surgery within the first week of admission to optimize visual outcome of such
      patients. The illustrative case further exemplifies the value of close
      interaction between members of the management team for optimal outcome.

PMID- 20140634
TI  - Patient selection for revascularization procedures in adult Moyamoya disease
      based on dynamic perfusion computerized tomography with acetazolamide challenge
      (PCTA).
AB  - The usefulness of dynamic perfusion computerized tomography for early diagnosis
      of stroke is well established. However, limited data exists to assess the value
      of PCT in the evaluation of patients with chronic cerebral ischemia. The purpose
      of the study was to assess the utility of perfusion computerized tomography with
      acetazolamide challenge (PCTA) in the evaluation of cerebral perfusion and
      cerebrovascular reserve (CVR) in adult Moyamoya patients. From 2005-2008, 41
      patients with Moyamoya were scrutinized by PCTA. Of these, 22 patients (12
      females, ten males, mean age 41 years) with ischemic symptoms from Moyamoya
      disease were found to have no response or decreased cerebrovascular flow post
      acetazolamide indicating compromised CVR. Eight had bilateral symptoms. Based on
      matching symptoms and decreased CVR on PCTA, those 22 patients underwent 30
      superficial temporal artery-to-middle cerebral artery (STA-MCA) by-pass (eight
      with bilateral abnormal PCTA had bilateral STA-MCA by-pass). After a mean follow
      up of 14 months (range, 3-36 months), no new strokes or symptoms were reported.
      Graft patency, as documented by postoperative computerized tomography angiography
      at a mean 12 weeks after surgery was 100%. Eight patients had postoperative PCTA
      documenting improved CVR after STA-MCA by-pass. At latest follow-up, none of the
      19 patients with PCTA findings suggestive of normal CVR had any ischemic
      symptoms. CVR testing by means of PCTA may have a key role in patient selection
      for revascularization surgery and postoperative follow-up. These promising
      results warrant further testing of the technique.

PMID- 20140632
TI  - Child and adolescent psychiatric genetics.
AB  - The current status of child and adolescent psychiatric genetics appears promising
      in light of the initiation of genome-wide association studies (GWAS) for diverse
      polygenic disorders and the molecular elucidation of monogenic Rett syndrome, for
      which recent functional studies provide hope for pharmacological treatment
      strategies. Within the last 50 years, tremendous progress has been made in
      linking genetic variation to behavioral phenotypes and psychiatric disorders. We
      summarize the major findings of the Human Genome Project and dwell on largely
      unsuccessful candidate gene and linkage studies. GWAS for the first time offer
      the possibility to detect single nucleotide polymorphisms and copy number
      variants without a priori hypotheses as to their molecular etiology. At the same
      time it is becoming increasingly clear that very large sample sizes are required
      in order to enable genome wide significant findings, thus necessitating further
      large-scaled ascertainment schemes for the successful elucidation of the
      molecular genetics of childhood and adolescent psychiatric disorders. We conclude
      by reflecting on different scenarios for future research into the molecular basis
      of early onset psychiatric disorders. This review represents the introductory
      article of this special issue of the European Child and Adolescent Psychiatry.

PMID- 20140633
TI  - Predicting adult emotional and behavioral problems from externalizing problem
      trajectories in a 24-year longitudinal study.
AB  - The aim of this study was to examine the prediction of adult behavioral and
      emotional problems from developmental trajectories of externalizing behavior in a
      24-years longitudinal population-based study of 2,076 children. The adult
      psychiatric outcome of these trajectories has not yet been examined. Trajectories
      of the four externalizing behavior types: aggression, opposition, property
      violations and status violations were determined separately through latent class
      growth analysis using data of five waves, covering ages 4-18 years. We used
      regression analyses to determine the associations between children's trajectories
      and adults' psychiatric problems based on the Adult Self-Report. The
      developmental trajectories of the four types of externalizing behavior mostly
      predicted intrusive, aggressive and rule-breaking behavior in adulthood. Non
      destructive behaviors in childhood such as opposition and status violations
      predict adult problems to a larger extent than destructive behaviors such as
      aggression and property violations. In general, children who develop through high
      level trajectories are likely to suffer from both internalizing and externalizing
      problem behavior in adulthood, regardless the direction of change (i.e.
      increasing/decreasing/persisting) of the high-level trajectory. We can conclude
      that the level rather than the developmental change of externalizing behavior
      problems has a larger impact on adult outcome.

PMID- 20140635
TI  - Quick PCR based diagnosis of typhoid using specific genetic markers.
AB  - A quick multiplex PCR based detection method was developed for early diagnosis of
      typhoid using specific genetic markers of S. typhi. Primers of tyv gene, flag
      gene, viaB gene and ratA gene confirmed the specificity and sensitivity of the
      PCR. The serum samples of the suspected typhoid patients were taken directly for
      PCR without culturing and isolating genomic DNA. Overall diagnosis required 2 h
      which is the least time ever reported for a PCR based methods. The sensitivity of
      the method is up to 5 fg genomic DNA. The genetic markers are specific and the
      four pairs of primers give selective amplification and differentiate S. typhi
      from closely related S. typhimurium.

PMID- 20140636
TI  - Regulation of human organic anion transporter 4 by protein kinase C and NHERF-1:
      altering the endocytosis of the transporter.
AB  - PURPOSE: Human organic anion transporter 4 (hOAT4) belongs to a family of organic
      anion transporters that play critical roles in the body disposition of clinically
      important drugs. We have previously shown that the activity of hOAT4 was down
      regulated by activation of PKC and up-regulated by PDZ protein NHERF-1. Here, we
      investigated the mechanisms underlying such regulations. METHODS: COS-7 cells
      expressing hOAT4 were treated with PKC activator phorbol 12-myristate 13-acetate
      (PMA) or transfected with dominant negative mutants of dynamin-2 or Eps15 or
      transfected with NHERF-1. The internalization and the function of hOAT4 were then
      determined. RESULTS: We showed that hOAT4 constitutively internalized from and
      recycled back to plasma membrane. Transfection of dominant negative mutants of
      dynamin-2 or Eps15 into the cells, all of which block clathrin-dependent
      endocytotic pathway, significantly blocked hOAT4 internalization. Treatment of
      cells with PMA accelerated hOAT4 internalization, whereas transfection of cells
      with NHERF-1 attenuated hOAT4 internalization. CONCLUSION: Our studies
      demonstrated that i) hOAT4 undergoes constitutive trafficking between cell
      surface and intracellular compartments, ii) hOAT4 internalization partly occurs
      through clathrin-dependent pathway, iii) the down-regulation of hOAT4 activity by
      activation of PKC and the up-regulation of hOAT4 activity by NHERF-1 are mediated
      through alteration of hOAT4 internalization.

PMID- 20140637
TI  - Hepatic disposition of ximelagatran and its metabolites in pig; prediction of the
      impact of membrane transporters through a simple disposition model.
AB  - PURPOSE: The double prodrug, ximelagatran, is bioconverted, via the intermediates
      ethylmelagatran and N-hydroxymelagatran, to the direct thrombin inhibitor,
      melagatran. The primary aim of this study was to investigate the hepatic
      metabolism and disposition of ximelagatran and the intermediates in pig. A
      secondary aim was to explore a simple in vitro methodology for quantitative
      investigations of the impact of membrane transporters on the disposition of
      metabolized drugs. METHODS: Porcine S1 (supernatant fraction obtained by
      centrifuging at 1,000 g for 10 min) liver fractions and hepatocytes were
      incubated in the absence and presence of known membrane transporter inhibitors.
      The in vitro kinetics and disposition were determined by simultaneously fitting
      the disappearance of ximelagatran and the appearance of the metabolites. RESULTS:
      In S1 liver fractions, the metabolism was significantly inhibited by co
      incubation of verapamil or ketoconazole, but not by erythromycin, quinine or
      quinidine. The disposition of ximelagatran and the intermediate metabolites in
      hepatocytes were influenced, to various degrees, by carrier-mediated transport
      processes. CONCLUSION: This work demonstrates that it is possible to obtain
      profound information on the general mechanisms that are important in the drug
      liver disposition using the combination of common in vitro systems and the simple
      disposition model proposed in this study.

PMID- 20140638
TI  - Executive functioning in children with Asperger syndrome, ADHD-combined type,
      ADHD-predominately inattentive type, and controls.
AB  - The purpose of the study was to evaluate neuropsychological and behavioral rating
      measures of executive functions (EF) in children with two subtypes of ADHD,
      Asperger syndrome (AS), and controls. Relative to the control group, the clinical
      groups experienced more difficulty in EF. The AS group showed the most difficulty
      in emotional control, behavioral regulation, fluid reasoning, and planning
      compared to the ADHD groups. Number of symptoms of ADHD or AS was found to be
      significantly related to ratings of difficulty with behavior regulation,
      metacognition, and general behavioral regulation across the sample. These
      findings indicate that children with AS or ADHD may have a differing EF profile
      and thus, may respond differentially to interventions.

PMID- 20140639
TI  - A simple and efficient method for preparation of isolated ovarian follicles for
      transmission electron microscopy.
AB  - OBJECTIVE: A simple method for preparation of isolated ovarian follicles for
      transmission electron microscopy (TEM) using transwell inserts is described.
      MATERIALS AND METHODS: Pre-antral follicles were enzymatically isolated from
      mouse ovaries and cultured overnight on transwell insert polyester membranes. The
      following day, isolated ovarian follicles were processed for TEM by moving the
      transwell insert through successive wells containing the fixation and embedding
      reagents. After polymerization of the resin, the polyester membrane with the
      follicles embedded in the resin was disengaged from the transwell unit. The resin
      was sectioned. Semi-thin sections were stained with toluidine blue while ultra
      thin sections were stained by uranyl acetate and examined by light microscopy and
      TEM, respectively. RESULTS: Isolated ovarian follicles were easily processed in
      groups for TEM. Follicles were well embedded and there appeared to be no loss of
      tissue during processing. The ultra-structure of processed isolated ovarian
      follicles was well preserved with little evidence of processing artifacts.
      CONCLUSIONS: In situ processing and preparation of isolated ovarian follicles by
      first allowing attachment on transwell insert membranes was shown to be a simple,
      rapid and effective method for TEM.

PMID- 20140640
TI  - Ovarian hyperstimulation syndrome: pathophysiology and prevention.
AB  - PURPOSE: To review and discuss the pathophysiology and prevention strategies for
      ovarian hyperstimulation syndrome (OHSS), which is a condition that may occur in
      up to 20% of the high risk women submitted to assisted reproductive technology
      cycles. METHODS: The English language literature on these topics were reviewed
      through PubMed and discussed with emphasis on recent data. RESULTS: The role of
      estradiol, luteinizing hormone, human chorionic gonadotropin (hCG), inflammatory
      mediators, the renin-angiotensin system and vascular endothelial growth factor is
      discussed in the pathophysiology of OHSS. In addition we consider the prevention
      strategies, including coasting, administration of albumin, renin-angiotensin
      system blockage, dopamine agonist administration, non-steroidal anti-inflammatory
      administration, GnRH antagonist protocols, reducing hCG dosage, replacement of
      hCG and in vitro maturation of oocytes (IVM). CONCLUSIONS: Among the many
      prevention strategies that have been discussed, the current evidence points to
      the replacement of hCG by GnRH agonists in antagonist cycles and the performance
      of IVM procedures as the safest approaches.

PMID- 20140641
TI  - Oocyte cryopreservation: is it time to remove its experimental label?
AB  - As more reproductive-age women survive cancer at the expense of gonadotoxic
      therapy, the need for viable fertility preservation options has become paramount.
      Embryo cryopreservation, often using donor sperm, has been the standard offered
      these women over the past 20 years. Preservation of unfertilized oocytes now
      represents an acceptable and often equally viable alternative, particularly for
      single women, due to technologic advances made in the past decade. Given such,
      oocyte cryopreservation's experimental designation and need for IRB approval
      should thus be revisited.

PMID- 20140642
TI  - Do Medicare Advantage enrollees tend to be admitted to hospitals with better or
      worse outcomes compared with fee-for-service enrollees?
AB  - The hospitals selected by or for Medicare beneficiaries might depend on whether
      the patient is enrolled in a Medicare Advantage (MA) plan. A theoretical model of
      profit maximization by MA plans takes into account the tradeoffs of consumer
      preferences for annual premium versus outcomes of care in the hospital and other
      attributes of the plan. Hospital discharge databases for 13 states in 2006,
      maintained by the Agency for Healthcare Research and Quality, are the main source
      of data. Risk-adjusted mortality rates are available for all non-maternity adult
      patients in each of 15 clinical categories in about 1,500 hospitals. All-adult
      postoperative safety event rates covering 9 categories of events are calculated
      for surgical cases in about 900 hospitals. Instrumental variables are used to
      address potential endogeneity of the choice of a MA plan. The key findings are
      these: enrollees in MA plans tend to be treated in hospitals with lower resource
      cost and higher risk-adjusted mortality compared to Fee-for-Service (FFS)
      enrollees. The risk-adjusted mortality measure is about 1.5 percentage points
      higher for MA plan enrollees than the overall mean of 4%. However, the rate of
      safety events in surgical patients favors MA plan enrollees--the rate is 1
      percentage point below the average of 3.5%. These discrepant results are
      noteworthy and are plausibly due to greater discretion by the health plan in
      approving patients for elective surgery and as well as selecting hospitals for
      surgical patients. Emergency patients are generally excluded for the safety
      outcome measures. In addition, the current mortality measures may not adequately
      represent all surgical patients. Such caveats should be prominently highlighted
      when presenting comparative data. With that proviso, the study justifies
      informing Medicare beneficiaries about the mortality and safety outcome measures
      for hospitals being used by a MA plan compared to hospitals used by FFS
      enrollees.

PMID- 20140643
TI  - Expression of Caenorhabditis elegans RNA-directed RNA polymerase in transgenic
      Drosophila melanogaster does not affect morphological development.
AB  - Drosophila melanogaster, along with all insects and the vertebrates, lacks an
      RdRp gene. We created transgenic strains of Drosophila melanogaster in which the
      rrf-1 or ego-1 RdRp genes from C. elegans were placed under the control of the
      yeast GAL4 upstream activation sequence. Activation of the gene was performed by
      crossing these lines to flies carrying the GAL4 transgene under the control of
      various Drosophila enhancers. RT-PCR confirmed the successful expression of each
      RdRp gene. The resulting phenotypes indicated that introduction of the RdRp genes
      had no effect on D. melanogaster morphological development.

PMID- 20140645
TI  - Atypical rectal bleeding: the challenge of diagnosing mild ulcerative colitis.

PMID- 20140644
TI  - The reliability of an education-related self-efficacy scale for people with
      psychiatric disabilities.
AB  - We investigated the reliability of the Education-related Self Efficacy Scale (ESS
      40), a measure of self-efficacy at a core task level designed for people with
      psychiatric disabilities. Sixty community residents with schizophrenia or
      schizoaffective disorder participated. The ESS-40 was administered twice via
      telephone interview. Short cycle test-retest reliability was very good for the
      total score and most items. The measure demonstrated signs of a coherent internal
      structure, adequate face validity, good client acceptability, and promising
      utility. The reliability evidence supports its use in community mental health
      services and in psychiatric rehabilitation settings. Sensitivity and predictive
      validity require further investigation.

PMID- 20140646
TI  - Taking a broad approach to public health program adaptation: adapting a family
      based diabetes education program.
AB  - Diabetes health disparities among Hispanic populations have been countered with
      federally funded health promotion and disease prevention programs. Dissemination
      has focused on program adaptation to local cultural contexts for greater
      acceptability and sustainability. Taking a broader approach and drawing on our
      experience in Mexican American communities at the U.S.-Mexico Border, we
      demonstrate how interventions are adapted at the intersection of multiple
      cultural contexts: the populations targeted, the community- and university-based
      entities designing and implementing interventions, and the field team delivering
      the materials. Program adaptation involves negotiations between representatives
      of all contexts and is imperative in promoting local ownership and program
      sustainability.

PMID- 20140647
TI  - Enhancing community capacity to support physical activity: the development of a
      community-based indoor-outdoor walking program.
AB  - The University at Albany Prevention Research Center, guided by a needs assessment
      in two underserved communities (one urban, one rural), initiated a pilot project
      that opened a public school for community walking in a rural setting. This study
      examined a 9-week program for potential barriers, benefits, influential factors,
      and the physical activity levels of program participants. Evaluation was based on
      daily logs, pedometer diaries, participant surveys, and focus groups. Results
      indicated that rural schools provide a useful resource for residents and increase
      participants' physical activity levels. A more comprehensive rural community
      walking program has been implemented as a result of these findings.

PMID- 20140648
TI  - Molecular cloning, characterization and expression of cDNA encoding
      translationally controlled tumor protein (TCTP) from Jatropha curcas L.
AB  - A cDNA encoding translationally controlled tumor protein (TCTP) of Jatropha
      curcas L., JcTCTP, was isolated from an endosperm cDNA library. JcTCTP consisted
      of a 5' untranslated region (UTR) of 526 bp, a 3' UTR of 377 bp and an open
      reading frame (ORF) of 507 bp, encoding a protein of 168 amino acid residues,
      which contained two signature sequences of TCTP family. Its deduced amino acid
      sequence was similar to the other known plants TCTPs in a range of 77.4-92.3%.
      Expression of JcTCTP was the highest in the stem, endosperm at embryo formation
      stage and embryo of J. curcas tissues, and the lowest in the endosperm at seminal
      leaf embryo stage and flower, demonstrating a pattern of temporal and spatial
      specific expression.

PMID- 20140649
TI  - The effects of elevated carbon dioxide levels on a Vibrio sp. isolated from the
      deep-sea.
AB  - INTRODUCTION: The effect of oceanic CO2 sequestration was examined exposing a
      deep-sea bacterium identified as Vibrio alginolyticus (9NA) to elevated levels of
      carbon dioxide and monitoring its growth at 2,750 psi (1,846 m depth). FINDINGS:
      The wild-type strain of 9NA could not grow in acidified marine broth below a pH
      of 5. The pH of marine broth did not drop below this level until at least 20.8 mM
      of CO2 was injected into the medium. 9NA did not grow at this CO2 concentration
      or higher concentrations (31.2 and 41.6 mM) for at least 72 h. Carbon dioxide at
      10.4 mM also inhibited growth, but the bacterium was able to recover and grow.
      Exposure to CO2 caused the cell to undergo a morphological change and form a
      dimple-like structure. The membrane was also damaged but with no protein leakage.

PMID- 20140650
TI  - Atmospheric polycyclic aromatic hydrocarbons in remote European and Atlantic
      sites located above the boundary mixing layer.
AB  - BACKGROUND, AIM AND SCOPE: Ambient air concentrations of polycyclic aromatic
      hydrocarbons (PAH) were determined at five elevated mountain sites on the
      European continent and the Atlantic Ocean. All sites can be considered remote
      background areas since they are situated above the timberline and they lack local
      emission sources of these compounds. RESULTS AND DISCUSSION: Average gas phase
      concentrations of SigmaPAH were 165, 1,475, 1,553, 1,822 and 4,443 pg m(-3) for
      Tenerife, Pyrenees, Central Norway, Tyrolean Alps and High Tatras, respectively.
      Particulate phase concentrations were 55, 70, 383, 196 and 708 pg m(-3),
      respectively. The PAH profiles of samples from the different sites are very
      similar, being typical of PAH mixtures after long-range atmospheric transport.
      Part of the fluctuations in PAH concentrations are explained by the influence of
      temperature on the particulate/gas phase partitioning. CONCLUSION: The
      differences in PAH levels between sites, with the lowest concentrations found in
      Tenerife and the highest in the High Tatras, suggest the geographical influence
      of regional emissions on the sites, especially in the cold periods and for the
      sites in the eastern sector of the European continent. This is supported by air
      mass back-trajectories analysis for the samples on the different sites. The
      influence of the continent is not detectable in the case of the elevated site of
      Tenerife where the free troposphere has been sampled. The results in this study
      are consistent with the PAH levels found in soils and/or high mountain lake
      sediments from these areas.

PMID- 20140652
TI  - Selenium modifies the effect of short-term chilling stress on cucumber plants.
AB  - The objective of this study was to investigate the effect of selenium (Se) supply
      (0, control; 2.5, 5, 10, or 20 MUM) on cucumber (Cucumis sativus L.) cv. Polan F1
      plants grown under short-term low temperature stress. About 14-16 day-old
      seedlings, grown at an optimal temperature (25/20 degrees C; day/night), were
      exposed to short-term chilling stress with a day/night temperature of 10 degrees
      C/5 degrees C for 24 h, for a further 24 h at 20 degrees C/15 degrees C, and then
      transferred to 25/20 degrees C (re-warming) for 7 days. Se did not affect the
      fresh weight (FW) of plants at a concentration of 2.5-10 MUM, but in the presence
      of 20 MUM Se, the biomass of shoots significantly decreased. The contents of
      chlorophylls and carotenoids witnessed no significant change after Se
      supplementation. Compared with the control, the Se-treated plants showed an
      increase of proline content in leaves, once after chilling and again after 7 days
      of re-warming. However, proline levels were much higher immediately after
      chilling than after re-warming. The malondialdehyde (MDA) content in the root of
      plants treated with 2.5-10 MUM Se decreased directly after stress. This was in
      comparison with the plants grown without Se, whereas it increased in roots and
      leaves of plants exposed to 20 MUM Se. Seven days later, the MDA level in the
      root of plants grown in the presence of Se was still lower than those of plants
      not treated with Se and generally witnessed no significant change in leaves.
      Although Se at concentrations of 2.5-10 MUM modified the physiological response
      of cucumber to short-term chilling stress, causing an increase in proline content
      in leaves and diminishing lipid peroxidation in roots, the resistance of plants
      to low temperature was not clearly enhanced, as concluded on the basis of FW and
      photosynthetic pigments accumulation.

PMID- 20140651
TI  - Potential physiological effects of pharmaceutical compounds in Atlantic salmon
      (Salmo salar) implied by transcriptomic analysis.
AB  - BACKGROUND, AIM, AND SCOPE: Pharmaceuticals are emerging pollutants widely used
      in everyday urban activities which can be detected in surface, ground, and
      drinking waters. Their presence is derived from consumption of medicines,
      disposal of expired medications, release of treated and untreated urban
      effluents, and from the pharmaceutical industry. Their growing use has become an
      alarming environmental problem which potentially will become dangerous in the
      future. However, there is still a lack of knowledge about long-term effects in
      non-target organisms as well as for human health. Toxicity testing has indicated
      a relatively low acute toxicity to fish species, but no information is available
      on possible sublethal effects. This study provides data on the physiological
      pathways involved in the exposure of Atlantic salmon as representative test
      species to three pharmaceutical compounds found in ground, surface, and drinking
      waters based on the evaluation of the xenobiotic-induced impairment resulting in
      the activation and silencing of specific genes. MATERIALS AND METHODS:
      Individuals of Atlantic salmon (Salmo salar) parr were exposed during 5 days to
      environmentally relevant concentrations of three representative pharmaceutical
      compounds with high consumption rates: the analgesic acetaminophen (54.77+/-34.67
      microg L(-1)), the anticonvulsant carbamazepine (7.85+/-0.13 microg L(-1)), and
      the beta-blocker atenolol (11.08+/-7.98 microg L(-1)). Five immature males were
      selected for transcriptome analysis in brain tissues by means of a 17k salmon
      cDNA microarray. For this purpose, mRNA was isolated and reverse-transcribed into
      cDNA which was labeled with fluorescent dyes and hybridized against a common pool
      to the arrays. Lists of significantly up- and down-regulated candidate genes were
      submitted to KEGG (Kyoto Encyclopedia of Genes and Genomes) in order to analyze
      for induced pathways and to evaluate the usefulness of this method in cases of
      not completely annotated test organisms. RESULTS: Exposure during 5 days to
      environmentally relevant concentrations of the selected pharmaceutical compounds
      acetaminophen, carbamazepine, and atenolol produced differences in the expression
      of 659, 700, and 480 candidate genes, respectively. KEGG annotation numbers (KO
      annotations) were obtained for between 26.57% and 33.33% of these differently
      expressed genes per treatment in comparison to non-exposure conditions. Pathways
      that showed to be induced did not always follow previously reported targets or
      metabolic routes for the employed treatments; however, several other pathways
      have been found (four or more features) to be significantly induced. DISCUSSION:
      Energy-related pathways have been altered under exposure in all the selected
      treatments, indicating a possible energy budget leakage due to additional
      processes resulting from the exposure to environmental contaminants. Observed
      induction of pathways may indicate additional processes involved in the mode of
      action of the selected pharmaceuticals which may not have been detected with
      conventional methods like quantitative PCR in which only suspected features are
      analyzed punctually for effects. The employment of novel high-throughput
      screening techniques in combination with global pathway analysis methods, even if
      the organism is not completely annotated, allows the examination of a much
      broader range of candidates for potential effects of exposure at the gene level.
      CONCLUSIONS: The continuously growing number of annotations of representative
      species relevant for environmental quality testing is facilitating pathway
      analysis processes for not completely annotated organisms. KEGG has shown to be a
      useful tool for the analysis of induced pathways from data generated by
      microarray techniques with the selected pharmaceutical contaminants
      acetaminophen, carbamazepine, and atenolol, but further studies have to be
      carried out in order to determine if a similar expression pattern in terms of
      fold change quantity and pathways is observed after long-term exposure. Together
      with the information obtained in this study, it will then be possible to evaluate
      the potential risk that the continuous release of these compounds may have on the
      environment and ecosystem functioning.

PMID- 20140653
TI  - Multiple endocrine neoplasms and serous cysts of the pancreas in a patient with
      von Hippel-Lindau disease.
AB  - INTRODUCTION: Patients with the von Hippel-Lindau (VHL) syndrome have an
      increased risk of developing pancreatic endocrine neoplasms. CASE REPORT: A 40
      year-old female with a past history of bilateral adrenal pheochromocytomas, whose
      brother had a history of a malignant pheochromocytoma, was referred to our
      institution with symptoms of adrenal crisis including general fatigue and
      insomnia in spite of increasing predonisolone therapy. Screening by ultrasonogram
      and computed tomography demonstrated multiple well-demarcated, enhancing nodules
      (maximum, 3 cm) in the head and tail of pancreas and multiple cystic lesions
      throughout the entire pancreas. Although this patient met the criteria for VHL,
      magnetic resonance imaging for her brain did not reveal any lesions.
      Pancreatoduodenectomy with partial distal pancreatectomy was performed.
      Histologic examination of the resected pancreas revealed multiple well
      differentiated endocrine neoplasms accompanied with multiple serous cysts. The
      patient remains free of disease 5 years after surgery.

PMID- 20140654
TI  - Letter to the editor: new equations for predicting postoperative risk in patients
      with hip fracture.

PMID- 20140655
TI  - Founding of the julius wolff institut charite - universitatsmedizin berlin:
      editorial comment.
AB  - This Editorial on Julius Wolff corresponds to a translation of the historic text,
      Zur Lehre von der Fracturenheilung, available at DOI 10.1007/s11999-010-1240-9 ;
      and a translation and abridgement of the historic text, Ueber die Innere
      Architectur der Knochen und ihre Bedeutung fur die Frage vom Knochenwachstum,
      available at DOI 10.1007/s11999-010-1239-2 . (Supplemental materials are
      available with the online version of CORR.) An accompanying biographical sketch
      is available at DOI 10.1007/s11999-010-1258-z .

PMID- 20140656
TI  - Systems biology of recombinant protein production in Bacillus megaterium.
AB  - Over the last two decades the Gram-positive bacterium Bacillus megaterium was
      systematically developed to a useful alternative protein production host.
      Multiple vector systems for high yield intra- and extracellular protein
      production were constructed. Strong inducible promoters were combined with DNA
      sequences for optimised ribosome binding sites, various leader peptides for
      protein export and N- as well as C-terminal affinity tags for affinity
      chromatographic purification of the desired protein. High cell density
      cultivation and recombinant protein production were successfully tested. For
      further system biology based control and optimisation of the production process
      the genomes of two B. megaterium strains were completely elucidated, DNA arrays
      designed, proteome, fluxome and metabolome analyses performed and all data
      integrated using the bioinformatics platform MEGABAC. Now, solid theoretical and
      experimental bases for primary modeling attempts of the production process are
      available.

PMID- 20140657
TI  - Analysis and engineering of metabolic pathway fluxes in Corynebacterium
      glutamicum.
AB  - The Gram-positive soil bacterium Corynebacterium glutamicum was discovered as a
      natural overproducer of glutamate about 50 years ago. Linked to the steadily
      increasing economical importance of this microorganism for production of
      glutamate and other amino acids, the quest for efficient production strains has
      been an intense area of research during the past few decades. Efficient
      production strains were created by applying classical mutagenesis and selection
      and especially metabolic engineering strategies with the advent of recombinant
      DNA technology. Hereby experimental and computational approaches have provided
      fascinating insights into the metabolism of this microorganism and directed
      strain engineering. Today, C. glutamicum is applied to the industrial production
      of more than 2 million tons of amino acids per year. The huge achievements in
      recent years, including the sequencing of the complete genome and efficient post
      genomic approaches, now provide the basis for a new, fascinating era of research 
      analysis of metabolic and regulatory properties of C. glutamicum on a global
      scale towards novel and superior bioprocesses.

PMID- 20140658
TI  - Integration of systems biology with bioprocess engineering: L: -threonine
      production by systems metabolic engineering of Escherichia coli.
AB  - Random mutation and selection or targeted metabolic engineering without
      consideration of its impact on the entire metabolic and regulatory networks can
      unintentionally cause genetic alterations in the region, which is not directly
      related to the target metabolite. This is one of the reasons why strategies for
      developing industrial strains are now shifted towards targeted metabolic
      engineering based on systems biology, which is termed systems metabolic
      engineering. Using systems metabolic engineering strategies, all the metabolic
      engineering works are conducted in systems biology framework, whereby entire
      metabolic and regulatory networks are thoroughly considered in an integrated
      manner. The targets for purposeful engineering are selected after all possible
      effects on the entire metabolic and regulatory networks are thoroughly
      considered. Finally, the strain, which is capable of producing the target
      metabolite to a high level close to the theoretical maximum value, can be
      constructed. Here we review strategies and applications of systems biology
      successfully implemented on bioprocess engineering, with particular focus on
      developing L: -threonine production strains of Escherichia coli.

PMID- 20140659
TI  - Multi-scale spatio-temporal modeling: lifelines of microorganisms in bioreactors
      and tracking molecules in cells.
AB  - Agent-based models are rigorous tools for simulating the interactions of
      individual entities, such as organisms or molecules within cells and assessing
      their effects on the dynamic behavior of the system as a whole. In context with
      bioprocess and biosystems engineering there are several interesting and important
      applications. This contribution aims at introducing this strategy with the aid of
      two examples characterized by striking distinctions in the scale of the
      individual entities and the mode of their interactions. In the first example a
      structured-segregated model is applied to travel along the lifelines of single
      cells in the environment of a three-dimensional turbulent field of a stirred
      bioreactor. The modeling approach is based on an Euler-Lagrange formulation of
      the system. The strategy permits one to account for the heterogeneity present in
      real reactors in both the fluid and cellular phases, respectively. The individual
      response of the cells to local variations in the extracellular concentrations is
      pictured by a dynamically structured model of the key reactions of the central
      metabolism. The approach permits analysis of the lifelines of individual cells in
      space and time.The second application of the individual modeling approach deals
      with dynamic modeling of signal transduction pathways in individual cells.
      Usually signal transduction networks are portrayed as being wired together in a
      spatially defined manner. Living circuitry, however, is placed in highly
      malleable internal architecture. Creating a homogenous bag of molecules, a well
      mixed system, the dynamic behavior of which is modeled with a set of ordinary
      differential equations is normally not valid. The dynamics of the MAP kinase and
      a steroid hormone pathway serve as examples to illustrate how single molecule
      tracking can be linked with the stochasticity of biochemical reactions, where
      diffusion and reaction occur in a probabilistic manner. The problem of hindered
      diffusion caused by macromolecular crowding is also taken into account.

PMID- 20140660
TI  - Cytotoxicity and genotoxicity reporter systems based on the use of mammalian
      cells.
AB  - With the dramatic increase in the number of new agents arising from the chemical,
      pharmaceutical, and agricultural industries, there is an urgent need to develop
      assays for rapid evaluation of potential risks to man and environment. The panel
      of conventional tests used for cytotoxicity and genotoxicity and the strategies
      to progress from small scale assays to high content screening in toxicology are
      discussed. The properties of components necessary as sensors and reporters for
      new reporter assays, and the application of genetic strategies to design assays
      are reviewed. The concept of cellular reporters is based on the use of promoters
      of chemical stress-regulated genes ligated to a suitable luminescent or
      fluorescent reporter gene. Current reporter assays designed from constructs
      transferred into suitable cell lines are presented.

PMID- 20140662
TI  - Marker-assisted characterization of durum wheat Langdon-Golden Ball disomic
      substitution lines.
AB  - The durum wheat cultivar 'Golden Ball' (GB) is a source of resistance to wheat
      sawfly due to its superior solid stem. In the late 1980s, Dr. Leonard Joppa
      developed a complete set of 14 'Langdon' (LDN)-GB disomic substitution (DS) lines
      by using GB as the chromosome donor and LDN as the recipient. However, these
      substitution lines have not been previously characterized and reported in the
      literature. The objectives of this study were to confirm the authenticity of the
      substituted chromosomes and to analyze the genetic background of the 14 LDN-GB DS
      lines with the aid of molecular markers, and to further use the substitution
      lines for chromosomal localization of DNA markers and genes conferring the
      superior stem solidness in GB. Results from simple sequence repeat marker
      analysis validated the authenticity of the substituted chromosomes in 14 LDN-GB
      DS lines. Genome-wide scans using the target region amplification polymorphism
      (TRAP) marker system produced a total of 359 polymorphic fragments that were used
      to compare the genetic background of substitution lines with that of LDN. Among
      the polymorphic TRAP markers, 134 (37.3%) and 185 (51.5%) were present in LDN and
      GB, respectively, with only 10 (2.8%) derived from Chinese Spring. Therefore,
      marker analysis demonstrated that each LDN-GB DS line had a pair of chromosomes
      from GB with a genetic background similar to that of LDN. Of the TRAP markers
      generated in this study, 200 were successfully assigned to specific chromosomes
      based on their presence or absence in the corresponding LDN-GB DS lines. Also,
      evaluation of stem solidness in the substitution lines verified the presence of a
      major gene for stem solidness in chromosome 3B. Results from this research
      provides useful information for the utilization of GB and LDN-GB DS lines for
      genetic and genomic studies in tetraploid wheat and for the improvement of stem
      solidness in both durum and bread wheat.

PMID- 20140661
TI  - Increased size of solid organs in patients with Chuvash polycythemia and in mice
      with altered expression of HIF-1alpha and HIF-2alpha.
AB  - Chuvash polycythemia, the first hereditary disease associated with dysregulated
      oxygen-sensing to be recognized, is characterized by a homozygous germ-line loss
      of-function mutation of the VHL gene (VHL(R200W)) resulting in elevated hypoxia
      inducible factor (HIF)-1alpha and HIF-2alpha levels, increased red cell mass and
      propensity to thrombosis. Organ volume is determined by the size and number of
      cells, and the underlying molecular control mechanisms are not fully elucidated.
      Work from several groups has demonstrated that the proliferation of cells is
      regulated in opposite directions by HIF-1alpha and HIF-2alpha. HIF-1alpha
      inhibits cell proliferation by displacing MYC from the promoter of the gene
      encoding the cyclin-dependent kinase inhibitor, p21(Cip1), thereby inducing its
      expression. In contrast, HIF-2alpha promotes MYC activity and cell proliferation.
      Here we report that the volumes of liver, spleen, and kidneys relative to body
      mass were larger in 30 individuals with Chuvash polycythemia than in 30 matched
      Chuvash controls. In Hif1a(+/-) mice, which are heterozygous for a null
      (knockout) allele at the locus encoding HIF-1alpha, hepatic HIF-2alpha mRNA was
      increased (2-fold) and the mass of the liver was increased, compared with wild
      type littermates, without significant difference in cell volume. Hepatic
      p21(Cip1) mRNA levels were 9.5-fold lower in Hif1a(+/-) mice compared with wild
      type littermates. These data suggest that, in addition to increased red cell
      mass, the sizes of liver, spleen, and kidneys are increased in Chuvash
      polycythemia. At least in the liver, this phenotype may result from increased HIF
      2alpha and decreased p21(Cip1) levels leading to increased hepatocyte
      proliferation.

PMID- 20140663
TI  - Prison suicide in 12 countries: an ecological study of 861 suicides during 2003
      2007.
AB  - BACKGROUND: Although suicide rates among prisoners are high and vary between
      countries, it is uncertain whether this reflects the importation of risk from the
      general population or is associated with incarceration rates. METHODS: We
      collected data on suicides and undetermined deaths in 12 countries (Australia,
      Belgium, Canada, Denmark, England and Wales, Finland, Ireland, Netherlands, New
      Zealand, Norway, Scotland, and Sweden) directly from their prison administrations
      for 2003-2007. These were compared with rates of suicides in the general
      population separately by gender using Pearson's correlations. In addition, they
      were compared with rates of incarceration. Linear regression was used to examine
      any association after adjustment for rates of incarceration. RESULTS: Data were
      collected on 861 suicides in prison, of which 810 were in men. In the men, crude
      relative rates of suicide were at least three times higher than the general
      population. Western European countries had similar rates of prisoner suicide
      which were mostly higher than those in Australia, Canada, and New Zealand. There
      was no association between rates of suicide in prisoners and general population
      rates or rates of incarceration. In the women, inmate suicide rates varied widely
      and were mostly raised compared with rates in the general population. In
      addition, these rates did not appear to be associated with general population
      rates of suicide. CONCLUSIONS: Rates of prison suicide do not reflect general
      population suicide rates, suggesting that variations in prison suicide rates
      reflect differences in criminal justice systems including, possibly, the
      provision of psychiatric care in prison.

PMID- 20140664
TI  - Automated mass spectrometric analysis of urinary and plasma serotonin.
AB  - Serotonin emerges as crucial neurotransmitter and hormone in a growing number of
      different physiologic processes. Besides extensive serotonin production
      previously noted in patients with metastatic carcinoid tumors, serotonin now is
      implicated in liver cell regeneration and bone formation. The aim was to develop
      a rapid, sensitive, and highly selective automated on-line solid-phase extraction
      method coupled to high-performance liquid chromatography-tandem mass spectrometry
      (XLC-MS/MS) to quantify low serotonin concentrations in matrices such as platelet
      poor plasma and urine. Fifty microliters plasma or 2.5 microL urine equivalent
      were pre-purified by automated on-line solid-phase extraction, using weak cation
      exchange. Chromatography of serotonin and its deuterated internal standard was
      performed with hydrophilic interaction chromatography. Mass spectrometric
      detection was operated in multiple reaction monitoring mode using a quadrupole
      tandem mass spectrometer with positive electrospray ionization. Serotonin
      concentrations were determined in platelet-poor plasma of metastatic carcinoid
      patients (n = 23) and healthy controls (n = 22). Urinary reference intervals were
      set by analyzing 24-h urine collections of 120 healthy subjects. Total run-time
      was 6 min. Intra- and inter-assay analytical variation were <10%. Linearity in
      the 0-7300 micromol/L calibration range was excellent (R(2) > 0.99).
      Quantification limits were 30 and 0.9 nmol/L in urine and plasma, respectively.
      Platelet-poor serotonin concentrations in metastatic carcinoid patients were
      significantly higher than in controls. The urinary reference interval was 10-78
      micromol/mol creatinine. Serotonin analysis with sensitive and specific XLC-MS/MS
      overcomes limitations of conventional HPLC. This enables accurate quantification
      of serotonin for both routine diagnostic procedures and research in serotonin
      related disorders.

PMID- 20140665
TI  - Analytical evaluation of a rapid on-site oral fluid drug test.
AB  - There is a need for a reliable rapid on-site oral fluid test that can be used in
      police controls to detect impaired drivers. We evaluated the Varian Oralab6 and
      collected two oral fluid samples from 250 subjects, one with the Varian Oralab6
      and one with the StatSure Saliva Sampler. The Oralab6 can detect six drug types:
      amphetamines, methamphetamine, cocaine, opiates, delta9-tetrahydrocannabinol
      (THC), and phencyclidine (PCP). On-site results were obtained within 10 to 15
      min. The sample collected with StatSure was analyzed using liquid chromatography
      tandem mass spectrometry after liquid-liquid extraction and these results were
      used as a reference to determine prevalence, sensitivity, and specificity. Two
      cut-off values were used in the evaluation. The Varian cut-off values were:
      amphetamine 50 ng/mL, cocaine 20 ng/mL, opiates 40 ng/mL, and THC 50 ng/mL. The
      DRUID cut-offs were: amphetamine 25 ng/mL, cocaine 20 ng/mL, opiates 20 ng/mL,
      and THC 1 ng/mL. Applying the first cut-offs, prevalence, sensitivity, and
      specificity were: amphetamine 10%, 76%, 100%; cocaine 23%, 34%, 100%; opiates
      38%, 83%, 94%; and THC 18%, 41%, 99%. The DRUID cut-off values gave the following
      results: amphetamine 14%, 56%, 100%; cocaine 28%, 34%, 100%; opiates 49%, 68%,
      98%, and THC 45%, 16%, 99%. The specificity of the Oralab6 is generally good. For
      both cut-offs, sensitivity was low for cocaine and THC. Therefore, the Varian
      Oralab6 test is not sensitive enough to be applied during roadside police
      controls.

PMID- 20140666
TI  - Colorimetric and electrochemical phosphodiesterase inhibition assays for
      yessotoxin detection: development and comparison with LC-MS/MS.
AB  - This work describes the development and applicability of two functional assays
      for the detection of yessotoxin (YTX), a polycyclic ether marine toxin produced
      by dinoflagellates. The assays are based on the interaction between this toxin
      and the phosphodiesterase (PDE) enzyme and the subsequent measurement of the
      enzyme activity by colorimetric and electrochemical methods. Firstly, several
      enzyme substrates were tested in order to select those able to be detected by
      colorimetry or electrochemistry after enzymatic hydrolysis. The substrates that
      provided the highest absorbance values and density currents were p-nitrophenyl
      phenylphosphonate and alpha-naphthyl phosphate, respectively. After optimisation
      of the experimental parameters, limits of detection of 0.8 and 0.6 microM were
      attained by colorimetry and electrochemistry, respectively. An inhibitory effect
      of YTX on the PDE activity was observed. The assays have been applied to the
      analysis of YTX production by Protoceratium reticulatum cultures, and results
      were compared with liquid chromatography-tandem mass spectrometry analysis.

PMID- 20140667
TI  - Interaction of a commercial lipid dispersion and local anesthetics in human
      plasma: implications for drug trapping by "lipid-sinks".
AB  - Interactions between Intralipid dispersion and local anesthetics (bupivacaine,
      prilocaine, and lidocaine) were investigated. The amount of bupivacaine (the most
      cardiotoxic analyte of the local anesthetics studied) entrapped in Intralipid in
      the presence of plasma was studied using an off-line filtration and solid phase
      extraction method combined with capillary zone electrophoresis for quantification
      of free unbound bupivacaine. To confirm interactions between the analytes and
      Intralipid at lower concentrations, direct injection mass spectrometry was used.
      The use of immobilized Intralipid chromatography-atmospheric pressure ionization
      ion trap mass spectrometry in the study of interactions between drugs and
      Intralipid dispersion is demonstrated. Finally, interactions between Intralipid
      dispersion and local anesthetics were investigated by electrokinetic capillary
      chromatography. The electrophoretic mobility of the Intralipid dispersed phase
      was calculated using the iterative procedure and a homologous series of alkyl
      phenyl benzoates (C(1)-C(6)), and the retention factors for the analytes were
      determined.

PMID- 20140668
TI  - Melatonin modulates hippocampus NMDA receptors, blood and brain oxidative stress
      levels in ovariectomized rats.
AB  - We investigated the effects of melatonin administration on ovariectomy-induced
      oxidative toxicity and N-methyl-D: -aspartate receptor (NMDAR) subunits in the
      blood of rats. Thirty-two rats were studied in three groups. The first and second
      groups were control and ovariectomized rats. Melatonin was daily administrated to
      the ovariectomized rats in the third group for 30 days. Blood, brain cortical and
      hippocampal samples were taken from the three groups after 30 days. Brain
      cortical, erythrocyte and plasma lipid peroxidation (LP) levels were higher in
      the ovariectomized group than in controls, although the LP level was decreased in
      the ovariectomized group with melatonin treatment. Brain cortical and plasma
      concentrations of vitamins A, C and E as well as the NMDAR 2B subunit were lower
      in the ovariectomized group than in controls, although, except for plasma vitamin
      C, they were increased by the treatment. Brain cortical and erythrocyte reduced
      glutathione (GSH) levels were lower in the ovariectomized group than in controls,
      although erythrocyte GSH levels were higher in the melatonin group than in the
      ovariectomized group. Brain cortical and erythrocyte glutathione peroxidase
      activity and NMDAR 2A subunit concentrations were not found to be different in
      all groups statistically. Oxidative stress has been proposed to explain the
      biological side effect of experimental menopause. Melatonin prevents experimental
      menopause-induced oxidative stress to strengthen antioxidant vitamin and NMDAR 2A
      subunit concentrations in ovariectomized rats.

PMID- 20140670
TI  - Valgus osteotomy in recent intracapsular femoral neck fractures.

PMID- 20140669
TI  - Effects of dithiothreitol on the amyloid fibrillogenesis of hen egg-white
      lysozyme.
AB  - At least 25 human proteins can fold abnormally to form pathological deposits that
      are associated with several degenerative diseases. Despite extensive
      investigation on amyloid fibrillation, the detailed molecular mechanisms remain
      rather elusive and there are currently no effective cures for treating these
      amyloid diseases. The present study examined the effects of dithiothreitol on the
      fibrillation of hen egg-white lysozyme (HEWL). Our results revealed that the
      fibrillation of hen lysozyme was significantly inhibited by reduced
      dithiothreitol (DTT(red)) while oxidized dithiothreitol (DTT(ox)) had no anti
      aggregating activity. Effective inhibitory activity against hen lysozyme
      fibrillation was observed only when DTT(red) was added within 8 days of
      incubation. Our results showed that the initial addition of DTT(red) interacted
      with HEWL, leading to a loss in conformational stability. It was concluded from
      our findings that DTT(red)-induced attenuation of HEWL fibrillation may be
      associated with disulfide disruption and extensive structural unfolding of HEWL.
      Our data may contribute to rational design of effective therapeutic strategies
      for amyloid diseases.

PMID- 20140672
TI  - Assessing public preferences for forest biomass based energy in the southern
      United States.
AB  - This article investigated public preferences for forest biomass based liquid
      biofuels, particularly ethanol blends of 10% (E10) and 85% (E85). We conducted a
      choice experiment study in three southern states in the United States: Arkansas,
      Florida, and Virginia. Reducing atmospheric CO(2), decreasing risk of wildfires
      and pest outbreaks, and enhancing biodiversity were presented to respondents as
      attributes of using biofuels. Results indicated that individuals had a positive
      extra willingness to pay (WTP) for both ethanol blends. The extra WTP was greater
      for higher blends that offered larger environment benefits. The WTPs for E10 were
      $0.56 gallon(-1), $0.58 gallon(-1), and $0.48 gallon(-1), and for E85 they were
      $0.82 gallon(-1), $1.17 gallon(-1), and $1.06 gallon(-1) in Arkansas, Florida,
      and Virginia, respectively. Although differences in WTP for E10 were
      statistically insignificant among the three states, significant differences were
      found in the WTP for E85 between AR and FL and between AR and VA. Preferences for
      the environmental attributes appeared to be heterogeneous, as respondents' were
      willing to pay a premium for E10 in all three states to facilitate the reduction
      of CO(2) and the improvement of biodiversity but were not willing to pay more for
      E85 in order to enhance biodiversity.

PMID- 20140671
TI  - Enhanced bone formation in large segmental radial defects by combining adipose
      derived stem cells expressing bone morphogenetic protein 2 with nHA/RHLC/PLA
      scaffold.
AB  - In this study, rabbit adipose-derived stem cells (rASCs) were isolated, cultured
      in vitro, and transfected with recombinant adenovirus vector containing human
      bone morphogenetic protein 2 (Ad-hBMP2). These cells were combined with a nano
      hydroxyapatite/recombinant human-like collagen/poly(lactic acid) scaffold
      (nHA/RHLC/PLA) to fabricate a new biocomposite (hBMP2/rASCs-nHA/RHLC/PLA, group
      1) and cultured in osteogenic medium. Non-transfected rASCs mixed with
      nHA/RHLC/PLA (rASCs-nHA/RHLC/PLA, group 2) and nHA/RHLC/PLA scaffold alone (group
      3) served as controls. Scanning electron microscope (SEM) demonstrated
      integration of rASCs with the nHA/RHLC/PLA scaffold. Quantitative real-time RT
      PCR analyses of collagen I, osteonectin, and osteopontin cDNA expression
      indicated that the osteogenic potency of rASCs was enhanced by transfection with
      Ad-hBMP2. After in vitro culture for seven days, three groups were implanted into
      15-mm length critical-sized segmental radial defects in rabbits. After 12 weeks,
      radiographic and histological analyses were performed. In group 1, the medullary
      cavity was recanalised, bone was rebuilt and moulding was finished, the bone
      contour had begun to remodel and scaffold was degraded completely. In contrast,
      bone defects were not repaired in groups 2 or 3. Furthermore, the scaffold
      degradation rate in group 1 was significantly higher than in groups 2 or 3. In
      summary, after transduction with Ad-hBMP2, the osteogenesis of rASCs was
      enhanced; a new biocomposite created with these cells induced repair of a
      critical bone defect in vivo in a relatively short time.

PMID- 20140673
TI  - An estimation of the effects of China's Priority Forestry Programs on farmers'
      income.
AB  - In the late 1990s, the Chinese government initiated some new programs and
      consolidated other existing ones of ecological restoration and resource
      development in its forest sector, and renamed them as "Priority Forestry
      Programs," or PFPs. They include the Natural Forest Protection Program (NFPP),
      the Sloping Land Conversion Program (SLCP), the Desertification Combating Program
      around Beijing and Tianjin (DCBT), the Shelterbelt Development Program (SBDP),
      and the Wildlife Conservation and Nature Reserve Development Program (WCNR). In
      addition to improving the environmental and resource conditions, a frequently
      reiterated goal of these PFPs is to increase rural households' income, therefore
      discussing why looking at rural household income impacts might be an important
      part of forest program evaluation. Thus, an interesting and important question
      is: How has implementing the PFPs affected the farmers' income and poverty
      status? This article addresses this question using a fixed-effects model and a
      panel dataset that covers 1968 households in four provinces for ten consecutive
      years (1995-2004). The empirical evidence indicates that their effects are mixed.
      The SLCP, the SBDP, and the NFPP have made positive impact and, by far, the SLCP
      has the largest effect. But the WCNR and the DCBT still have not had a pronounced
      overall effect due to their short time span of execution, even though they may
      have exerted certain influence at the margin. Notably, the impact of the WCNR, if
      any, is negative.

PMID- 20140674
TI  - Index of alien impact: a method for evaluating potential ecological impact of
      alien plant species.
AB  - Alien plant species are stressors to ecosystems and indicators of reduced
      ecosystem integrity. The magnitude of the stress reflects not only the quantity
      of aliens present, but also the quality of their interactions with native
      ecosystems. We develop an Index of Alien Impact (IAI) to estimate the collective
      ecological impact of in situ alien species. IAI summarizes the frequency of
      occurrence and potential ecological impact (Invasiveness-Impact Score (I ( i )))
      of individual alien species for all aliens present in a particular location or
      community type. A component metric, I (i), is based on ecological species traits
      (life history, ecological amplitude, and ability to alter ecosystem processes)
      that reflect mechanisms, which can increase impact to ecosystem structure and
      function. While I (i) is less complex than some other multi-metric rankings of
      alien impact, it compares well to these metrics and to qualitative judgments. IAI
      can be adapted for different ecological settings by modifying the set of species
      traits incorporated in I (i) to reflect properties likely to breach biotic and
      abiotic barriers or alter ecosystem function in a particular region or community
      type of interest. To demonstrate our approach, we created versions of IAI and I
      (i), applicable to the diverse streamside vegetation of a river basin (19,631
      km(2)) spanning low-elevation arid to mesic montane habitats in eastern Oregon,
      USA. In this demonstration effort, we (1) evaluate relationships of IAI to
      metrics describing invasion level, and (2) illustrate the potential utility of
      IAI for prioritizing alien species management activities and informing
      restoration goals.

PMID- 20140675
TI  - JAX Colony Management System (JCMS): an extensible colony and phenotype data
      management system.
AB  - The Jackson Laboratory Colony Management System (JCMS) is a software application
      for managing data and information related to research mouse colonies, associated
      biospecimens, and experimental protocols. JCMS runs directly on computers that
      run one of the PC Windows operating systems, but can be accessed via web browser
      interfaces from any computer running a Windows, Macintosh, or Linux operating
      system. JCMS can be configured for a single user or multiple users in small- to
      medium-size work groups. The target audience for JCMS includes laboratory
      technicians, animal colony managers, and principal investigators. The application
      provides operational support for colony management and experimental workflows,
      sample and data tracking through transaction-based data entry forms, and date
      driven work reports. Flexible query forms allow researchers to retrieve database
      records based on user-defined criteria. Recent advances in handheld computers
      with integrated barcode readers, middleware technologies, web browsers, and
      wireless networks add to the utility of JCMS by allowing real-time access to the
      database from any networked computer.

PMID- 20140676
TI  - Target-approaching behavior of barn owls (Tyto alba): influence of sound
      frequency.
AB  - We studied the influence of frequency on sound localization in free-flying barn
      owls by quantifying aspects of their target-approaching behavior to a distant
      sound source during ongoing auditory stimulation. In the baseline condition with
      a stimulus covering most of the owls hearing range (1-10 kHz), all owls landed
      within a radius of 20 cm from the loudspeaker in more than 80% of the cases and
      localization along the azimuth was more accurate than localization in elevation.
      When the stimulus contained only high frequencies (>5 kHz) no changes in striking
      behavior were observed. But when only frequencies from 1 to 5 kHz were presented,
      localization accuracy and precision decreased. In a second step we tested whether
      a further border exists at 2.5 kHz as suggested by optimality models. When we
      compared striking behavior for a stimulus having energy from 2.5 to 5 kHz with a
      stimulus having energy between 1 and 2.5 kHz, no consistent differences in
      striking behavior were observed. It was further found that pre-takeoff latency
      was longer for the latter stimulus than for baseline and that center frequency
      was a better predictor for landing precision than stimulus bandwidth. These data
      fit well with what is known from head-turning studies and from neurophysiology.

PMID- 20140677
TI  - Intralateral hypothalamic area injection of isoproterenol and propranolol affects
      food and water intake in broilers.
AB  - The role played by adrenergic system in water intake, especially food intake, has
      long been known in mammals. In avian species, there have been many experiments
      exploring the effects of the adrenergic system in different sites in the central
      nervous system in meat- and egg-type poultry. This study was designed to examine
      the possible effects of intralateral hypothalamic area (ILHy) microinjections of
      a beta-adrenergic agonist, isoproterenol, and a beta-adrenoceptor blocker,
      propranolol, on food and water intake in 3-h food-deprived and 3-h water-deprived
      broiler cockerels. Our findings suggest that the beta-adrenergic system directly
      affects food especially water intake in broilers. Although isoproterenol
      significantly (P < or = 0.05) decreased food intake for the first 15 min, it
      reduced food intake during the experiment. Isoproterenol reduced water intake
      significantly (P < or = 0.05), which was abolished by pretreatment with
      propranolol. It is proposed that beta-adrenoceptors in LHy play a direct and
      indirect role in the regulation of food especially water intake in broiler
      cockerels.

PMID- 20140678
TI  - Postnatal development of muscle biochemistry in nursing harbor seal (Phoca
      vitulina) pups: limitations to diving behavior?
AB  - Adult marine mammal muscles rely upon a suite of adaptations for sustained
      aerobic metabolism in the absence of freely available oxygen (O(2)). Although the
      importance of these adaptations for supporting aerobic diving patterns of adults
      is well understood, little is known about postnatal muscle development in young
      marine mammals. However, the typical pattern of vertebrate muscle development,
      and reduced tissue O(2) stores and diving ability of young marine mammals suggest
      that the physiological properties of harbor seal (Phoca vitulina) pup muscle will
      differ from those of adults. We examined myoglobin (Mb) concentration, and the
      activities of citrate synthase (CS), beta-hydroxyacyl coA dehydrogenase (HOAD),
      and lactate dehydrogenase (LDH) in muscle biopsies from harbor seal pups
      throughout the nursing period, and compared these biochemical parameters to those
      of adults. Pups had reduced O(2) carrying capacity ([Mb] 28-41% lower than
      adults) and reduced metabolically scaled catabolic enzyme activities (LDH/RMR 20
      58% and CS/RMR 29-89% lower than adults), indicating that harbor seal pup muscles
      are biochemically immature at birth and weaning. This suggests that pup muscles
      do not have the ability to support either the aerobic or anaerobic performance of
      adult seals. This immaturity may contribute to the lower diving capacity and
      behavior in younger pups. In addition, the trends in myoglobin concentration and
      enzyme activity seen in this study appear to be developmental and/or exercise
      driven responses that together work to produce the hypoxic endurance phenotype
      seen in adults, rather than allometric effects due to body size.

PMID- 20140679
TI  - Serum profiles of monocyte chemoattractant protein-1 as a biomarker for patients
      recovering from myocardial infarction.
AB  - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays a key role in the
      pathogenesis of atherosclerosis and has been proposed as a biomarker for patients
      with cardiovascular disease. METHODS: To assess its clinical usefulness, serum
      MCP-1 concentrations were measured in patients with ST-elevation myocardial
      infarction (MI) at admission, immediately after percutaneous coronary
      intervention (PCI), at 24 h, and after 6 months. RESULTS: We found no differences
      in MCP-1 concentrations between patients with acute MI, patients with stable
      coronary artery disease and healthy individuals. Although median MCP-1
      concentrations in patients with MI were similar at admission and after 6 months,
      there were significant differences between individuals in how MCP-1 levels
      changed with time. As demonstrated by comparing baseline quartiles of MCP-1, the
      levels of MCP-1 tended to increase in patients with low MCP-1 concentration at
      admission, and decrease in patients with initially high MCP-1 levels. We found an
      inverse correlation between MCP-1 concentration at baseline and the time to
      reperfusion, and detected a significant decrease in MCP-1 concentration
      immediately after PCI. We also observed lower MCP-1 concentrations over time in
      patients who developed restenosis within 6 months. However, we did not confirm
      the association between MCP-1 concentrations at baseline and a number of
      previously implicated demographic, clinical and laboratory criteria. CONCLUSIONS:
      Our data demonstrate some new aspects of MCP-1 measurement in patients with MI,
      but do not corroborate many earlier observations.

PMID- 20140680
TI  - In vitro interactions between aged garlic extract and drugs used for the
      treatment of cardiovascular and diabetic patients.
AB  - BACKGROUND: Disease preventing effects gained by garlic consumption have been
      recognized since early period of history, making commercially available garlic
      supplements attractive to the general public. Possible pharmacokinetic
      interactions which could occur between applied drugs and aged garlic extract
      (AGE) are unknown. AIM: To test in vitro impact of some garlic phytochemicals on
      P-glycoprotein (Pgp), the most recognized efflux transporter, and the effect of
      AGE on passive membrane permeability, absorptive and secretory intestinal
      transporters. METHODS: Rat small intestine and Caco-2 cell monolayers, mounted in
      side-by-side diffusion chambers were used. RESULTS: Hydrophilic sulphur compounds
      increased Pgp mediated Rhodamine 123 (Rho123) efflux, whereas the lipophilic ones
      increased Pgp efflux through rat ileum but not through Caco-2 cell monolayers.
      Increased activities of secretory (Pgp, multidrug-resistance associated protein
      2) and absorptive (monocarboxylate transporter 1, organic anion transporting
      polypeptide) transporters involved in drug absorption were observed in rat small
      intestine and Caco-2 cell monolayers in the presence of AGE. Transport of drugs
      mediated by breast cancer resistance protein and H(+)-oligopeptide transporter 1
      was activated in rat intestine but inhibited through Caco-2 cells. Passive
      membrane permeability of tested compounds remained unaltered through rat small
      intestine, while significant changes were observed with Caco-2 cell monolayers.
      CONCLUSIONS: Due to the observed in vitro pharmacokinetic interactions between
      AGE and investigated cardiovascular, antidiabetic and antiviral drugs, in vivo
      absorption changes are possible, but the magnitude of change depends on the most
      profound process involved (influx, efflux, passive diffusion) in compounds
      permeability.

PMID- 20140681
TI  - Reduction of hypoxia-induced angiogenesis in ovarian cancer cells by inhibition
      of HIF-1 alpha gene expression.
AB  - PURPOSE: The goal of this study was to investigate the effects of silencing HIF-1
      alpha gene expression with specific small interfering RNA (siRNA) on VEGF
      production and angiogenesis in epithelial ovarian cancer (EOC) cells. METHODS:
      Two EOC cell lines, MDAH-2774 and SKOV-3, were cultured under normoxic (20% O(2))
      and hypoxic (2% O(2)) conditions using standard techniques. After EOC cells were
      transfected with siRNA, HIF-1 alpha and VEGF mRNA levels were measured by real
      time RT-PCR. Angiogenesis was evaluated utilizing an in vitro assay model
      consisting of human umbilical vein endothelial cells (HUVEC) and polymerized ECM
      Matrix. RESULTS: Both EOC cell lines evaluated constitutively expressed HIF-1
      alpha and VEGF mRNA. HIF-1 alpha and VEGF mRNA levels were significantly
      increased in response to hypoxia (P < 0.05). Under hypoxic conditions, inhibition
      of HIF-1 alpha gene expression by a specific siRNA resulted in a significant
      reduction in HIF-1 alpha and VEGF mRNA levels (P < 0.05). In the in vitro
      angiogenesis model, supernatant from the hypoxic EOC cells induced the HUVEC to
      form a complex tubular network, a hallmark of angiogenesis. Semi-quantitative
      analysis of the angiogenesis assay revealed a significant reduction in tube
      formation when supernatant from HIF-1 alpha siRNA-treated hypoxic EOC cell was
      used (P < 0.05). CONCLUSION: Inhibition of HIF-1 alpha expression by specific
      siRNA resulted in a significant decrease in VEGF production and angiogenesis.
      Further investigation of HIF-1 alpha inhibition for anti-tumor activity is
      warranted and may potentially prove HIF-1 alpha as a therapeutic target in the
      management ovarian cancer.

PMID- 20140682
TI  - Short-term exercise training does not improve whole-body heat loss when rate of
      metabolic heat production is considered.
AB  - We evaluated the effects of an 8-week exercise training program in previously
      sedentary individuals on whole-body heat balance during exercise at a constant
      rate of metabolic heat production. Prior to and after 8 weeks of training, ten
      participants performed 60-min of cycling exercise at a constant rate of heat
      production (approximately 450 W) followed by 60-min of recovery, at 30 degrees C
      and 15% relative humidity. Rate of total heat loss was measured directly by whole
      body calorimetry, while rate of metabolic heat production was measured
      simultaneously by indirect calorimetry. Esophageal (T(es)), skin blood flow
      (SkBF) and local sweat rate (LSR) were also measured continuously. The 8-week
      exercise training program elicited a 10% increase in maximal aerobic capacity (P
      < 0.001). Furthermore, exercise training reduced (P <or= 0.05) baseline (37.10 +/
      0.28 vs. 36.95 +/- 0.24 degrees C) and end-exercise (37.85 +/- 0.30 vs. 37.55 +/
      0.20 degrees C) values for T (es) as well as onset thresholds for LSR (37.23 +/-
      0.26 vs. 36.96 +/- 0.22 degrees C, P < 0.001) and SkBF (37.16 +/- 0.38 vs. 36.83
      +/- 0.26 degrees C, P < 0.001). However, these improvements in thermoregulatory
      function did not translate into a greater rate of total heat loss between the pre
      and post-training exercise trials (P = 0.762). Furthermore, there were no
      differences in SkBF (P = 0.546) and LSR (P = 0.475) from pre- to post-training.
      Although physical training resulted in significant improvements of
      cardiorespiratory and thermoregulatory functions, these adaptations did not
      improve whole-body and local heat loss responses during exercise performed at a
      given rate of metabolic heat production.

PMID- 20140683
TI  - The effect of strength training and short-term detraining on maximum force and
      the rate of force development of older men.
AB  - This study examined the effect of strength training (ST) and short-term
      detraining on maximum force and rate of force development (RFD) in previously
      sedentary, healthy older men. Twenty-four older men (70-80 years) were randomly
      assigned to a ST group (n = 12) and C group (control, n = 12). Training consisted
      of three sets of six to ten repetitions on an incline squat at 70-90% of one
      repetition maximum three times per week for 16 weeks followed by 4 weeks of
      detraining. Regional muscle mass was assessed before and after training by dual
      energy X-ray absorptiometry. Training increased RFD, maximum bilateral isometric
      force, and force in 500 ms, upper leg muscle mass and strength above pre-training
      values (14, 25, 22, 7, 90%, respectively; P < 0.05). After 4 weeks detraining all
      neuromuscular variables were significantly (P < 0.05) lower than after 16 weeks
      training but remained significantly (P < 0.05) higher than pre-training levels
      except for RFD which had returned to pre-training levels. These findings
      demonstrate that high-intensity ST can improve maximum force and RFD of older
      men. However, older individuals may lose some neuromuscular performance after a
      period of short-term detraining and that resistance exercise should be performed
      on a regular basis to maintain training adaptations.

PMID- 20140685
TI  - A cold-adapted reptile becomes a more effective thermoregulator in a thermally
      challenging environment.
AB  - Thermoregulation is of great importance for the survival and fitness of
      ectotherms as physiological functions are optimized within a narrow range of body
      temperature (T(b)). The precision with which reptiles thermoregulate has been
      proposed to be related to the thermal quality of their environments. Although a
      number of studies have looked at the effect of thermal constraints imposed by
      diel, seasonal and altitudinal variation on thermoregulatory strategies, few have
      addressed this question in a laboratory setting. We conducted a laboratory
      experiment to test whether tuatara, Sphenodon punctatus (order Rhynchocephalia),
      a cold-adapted reptile endemic to New Zealand, modify their thermoregulatory
      behaviour in response to different thermal environments. We provided tuatara with
      three thermal treatments: high-quality habitat [preferred T(b) (T(sel)) could be
      reached for 8 h/day], medium-quality habitat (T(sel) available for 5 h/day) and
      low-quality habitat (T(sel) available for 3 h/day). All groups maintained body
      mass, but tuatara in the low-quality habitat thermoregulated more accurately and
      tended to maintain higher T (b)s than tuatara in the high-quality habitat. This
      study thus provides experimental evidence that reptiles are capable of adjusting
      their thermoregulatory behaviour in response to different thermal constraints.
      This result also has implications for the conservation of tuatara. A proposed
      translocation from their current habitat to a higher latitudinal range within New
      Zealand (similar to the shift from our 8 h/day to our 5 h/day regime) is unlikely
      to induce thermoconformity; rather, tuatara will probably engage in more
      effective thermoregulatory behaviour.

PMID- 20140686
TI  - The treatment of co-morbidities in older patients with metastatic cancer.
AB  - PURPOSE: The purpose of the study was to determine whether older patients with
      metastatic cancer continue to take medications for the treatment of pre-existing
      co-morbidities after the diagnosis of metastatic disease. METHODS: Between
      November 2008 and June 2009, patients over the age of 65 with metastatic cancer
      were interviewed. Medical records were reviewed in order to ascertain current
      medication use and relevant past medical history. Classes of medication of
      interest were prospectively defined; these were anti-hypertensives, lipid
      lowering drugs, anti-platelet agents, anti-coagulants and bisphosphonates.
      RESULTS: One hundred patients were recruited, with a median age of 73.5 years
      (range 65-88); 52% were women. The primary cancer sites were breast, 36%;
      prostate, 27%; colon, 14%; other, 23%. The median performance status of the
      patients was 2. The median number of medications was 7 (range 1-17). Eighty-one
      percent of patients were found to be taking one or more of the predefined
      medications for treatment of a long-term co-morbidity. Overall 52% of patients
      had side effects attributed to these medications. CONCLUSIONS: Patients with
      metastatic cancer continue to take drugs for prevention of co-morbidities which
      are associated with side effects and inconvenience. The benefits of these drugs
      are likely to be minimal, and medication reviews should be undertaken to address
      their appropriateness.

PMID- 20140684
TI  - Gap junctions in inherited human disease.
AB  - Gap junctions (GJ) provide direct intercellular communication. The structures
      underlying these cell junctions are membrane-associated channels composed of six
      integral membrane connexin (Cx) proteins, which can form communicating channels
      connecting the cytoplasms of adjacent cells. This provides coupled cells with a
      direct pathway for sharing ions, nutrients, or small metabolites to establish
      electrical coupling or balancing metabolites in various tissues. Genetic
      approaches have uncovered a still growing number of mutations in Cxs related to
      human diseases including deafness, skin disease, peripheral and central
      neuropathies, cataracts, or cardiovascular dysfunctions. The discovery of a
      growing number of inherited human disorders provides an unequivocal demonstration
      that gap junctional communication is crucial for diverse physiological processes.

PMID- 20140687
TI  - A diketoreductase exhibits unique renaturation profile from thermal-induced
      protein unfolding.
AB  - Proteins can refold from thermal-induced denaturation. Apo-diketoreductase
      exhibited a unique refolding profile, in which the degree of refolding from
      higher temperature was more complete. Partial aggregation and structural change
      may provide possible explanation on this phenomenon.

PMID- 20140688
TI  - Exploring the cause of drug resistance by the detrimental missense mutations in
      KIT receptor: computational approach.
AB  - In this work, we computationally identified the most detrimental missense
      mutations of KIT receptor causing gastrointestinal stromal tumors and analyzed
      the drug resistance of these missense mutations. Out of 31 missense mutations, 19
      variants were commonly found less stable, deleterious and damaging by I-Mutant
      2.0, SIFT and PolyPhen programs, respectively. Subsequently, we performed
      modeling of these 19 variants to understand their change in conformations with
      respect to native KIT receptor by computing their RMSD. Further, the native and
      19 mutants were docked with the drug 'Imatinib' to explain the drug resistance of
      these detrimental missense mutations. Among the 19 mutants, we found by docking
      studies that 12 mutants, namely, F584C, F584L, V654A, L656P, T670I, R804W, D816F,
      D816V, D816Y, N822K, Y823D and E839K had less binding affinity with Imatinib than
      the native type. Finally, we analyzed that the loss of binding affinity of these
      12 mutants, was due to altered flexibility in their binding amino acids with
      Imatinib as compared with native type by normal mode analysis. In our work, we
      found the novel data that the majority of the drug-binding amino acids in those
      12 mutants had encountered loss of flexibility, which could be the theoretical
      basis for the cause of drug insensitivity.

PMID- 20140689
TI  - Biochemical characteristics and inhibitor selectivity of mouse indoleamine 2,3
      dioxygenase-2.
AB  - The first step in the kynurenine pathway of tryptophan catabolism is the cleavage
      of the 2,3-double bond of the indole ring of tryptophan. In mammals, this
      reaction is performed independently by indoleamine 2,3-dioxygenase-1 (IDO1),
      tryptophan 2,3-dioxygenase (TDO) and the recently discovered indoleamine 2,3
      dioxygenase-2 (IDO2). Here we describe characteristics of a purified recombinant
      mouse IDO2 enzyme, including its pH stability, thermal stability and structural
      features. An improved assay system for future studies of recombinant/isolated
      IDO2 has been developed using cytochrome b (5) as an electron donor. This, the
      first description of the interaction between IDO2 and cytochrome b (5), provides
      further evidence of the presence of a physiological electron carrier necessary
      for activity of enzymes in the "IDO family". Using this assay, the kinetic
      activity and substrate range of IDO2 were shown to be different to those of IDO1.
      1-Methyl-D-tryptophan, a current lead IDO inhibitor used in clinical trials, was
      a poor inhibitor of both IDO1 and IDO2 activity. This suggests that its
      immunosuppressive effect may be independent of pharmacological inhibition of IDO
      enzymes, in the mouse at least. The different biochemical characteristics of the
      mouse IDO proteins suggest that they have evolved to have distinct biological
      roles.

PMID- 20140690
TI  - Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity
      on bacteria, protozoan parasites, insects, and human cancer cells.
AB  - Cupiennin 1a, a cytolytic peptide isolated from the venom of the spider
      Cupiennius salei, exhibits broad membranolytic activity towards bacteria,
      trypanosomes, and plasmodia, as well as human blood and cancer cells. In
      analysing the cytolytic activity of synthesised all-D: - and all-L: -cupiennin 1a
      towards pro- and eukaryotic cells, a stereospecific mode of membrane destruction
      could be excluded. The importance of negatively charged sialic acids on the outer
      leaflet of erythrocytes for the binding and haemolytic activity of L: -cupiennin
      1a was demonstrated. Reducing the overall negative charges of erythrocytes by
      partially removing their sialic acids or by protecting them with tri- or
      pentalysine results in reduced haemolytic activity of the peptide.

PMID- 20140691
TI  - Expressions of IL-18 and its binding protein in peripheral blood leukocytes and
      kidney tissues of lupus nephritis patients.
AB  - To investigate the expressions of IL-18 and its binding protein (IL-18BP) in
      peripheral blood leukocytes and kidney tissues in patients with lupus nephritis
      (LN). SYBR-green-dye-I-based real-time quantitative PCR method was used to
      compare the gene expression levels (indicated as 2(-DeltaDeltaCT) value) of IL-18
      and IL-18BP in the peripheral blood leucocytes of LN patients and those in normal
      controls. Serum levels of IL-18 were measured with ELISA method.
      Immunohistochemical evaluation of IL-18 and Il-18BP expression in LN was carried
      out on frozen renal biopsy sections. IL-18BP mRNA expression levels in LN
      patients were significantly lower than those of normal controls (P < 0.01). Serum
      levels of IL-18 in LN patients were significantly higher than those of normal
      controls (P < 0.01). It is noticeable that serum IL-18 levels in the patients
      treated with glucocorticoids and cyclophosphamide was lower than those treated
      with glucocorticoids only or glucocorticoids and other immune inhibitors such as
      chloroquine/hydroxychloroquine and azathioprine. Expression of IL-18 in renal
      glomeruli was higher in type-IV and type-V LN patients than in type-III LN
      patients. LN patients present lower IL-18BP mRNA expression and higher serum
      levels of IL-18 than those in normal controls. The preponderance of IL-18 in
      glomeruli from LN patients indicates IL-18 may be concerned with the local
      inflammation. Up-regulation of IL-18BP expression and control of the biological
      activity of IL-18 may be a therapeutic approach to LN patients.

PMID- 20140692
TI  - Anti-influenza vaccination in systemic lupus erythematosus patients: an analysis
      of specific humoral response and vaccination safety.
AB  - The objective of this study is to evaluate efficacy and safety of influenza
      vaccine in systemic lupus erythematosus (SLE) patients. We studied SLE patients
      and healthy subjects immunised with inactivated influenza vaccine. Efficacy was
      measured by comparing humoral response to vaccine antigens between groups. Safety
      was monitored by SLEDAI and serological markers. Subjects attended visits at
      baseline and on post-vaccination weeks 4 and 12. We enrolled 62 SLE patients and
      47 healthy subjects. In post-immunisation week 4, anti-haemagglutinin antibody
      titres rose in the patient group at least 6.23-fold, compared to 11.90-fold among
      controls (P < or = 0.05). The seroconversion rate range was 53-56% among patients
      and 72-85% among controls (P < 0.05 for strains H1N1 and H3N2, NS for strain type
      B). The seroprotection rate ranged between 62% and 73% and between 90% and 98% in
      the patient and control group, respectively (P < 0.05). In post-vaccination week
      12, the antibody titre was higher at least 3.86-fold in the patient group and
      7.65-fold among controls. The seroconversion rate range was 32-40% among patients
      and 64-70% among controls, while the seroprotection rate ranged between 43% and
      50% and between 79% and 94%, respectively (P < 0.005 for three strains). We
      identified one severe and six mild to moderate SLE exacerbations by week 12. The
      anti-nuclear antibodies and anti-double-stranded DNA titres grew by post
      immunisation week 4 (P < 0.05). The post-vaccination response was weaker in SLE
      patients compared to healthy subjects. Immunisation did not change underlying
      disease activity.

PMID- 20140693
TI  - Characteristics of implicit chaining in cotton-top tamarins (Saguinus oedipus).
AB  - In human cognition there has been considerable interest in observing the
      conditions under which subjects learn material without explicit instructions to
      learn. In the present experiments, we adapted this issue to nonhumans by asking
      what subjects learn in the absence of explicit reinforcement for correct
      responses. Two experiments examined the acquisition of sequence information by
      cotton-top tamarins (Saguinus oedipus) when such learning was not demanded by the
      experimental contingencies. An implicit chaining procedure was used in which
      visual stimuli were presented serially on a touchscreen. Subjects were required
      to touch one stimulus to advance to the next stimulus. Stimulus presentations
      followed a pattern, but learning the pattern was not necessary for reinforcement.
      In Experiment 1 the chain consisted of five different visual stimuli that were
      presented in the same order on each trial. Each stimulus could occur at any one
      of six touchscreen positions. In Experiment 2 the same visual element was
      presented serially in the same five locations on each trial, thereby allowing a
      behavioral pattern to be correlated with the visual pattern. In this experiment
      two new tests, a Wild-Card test and a Running-Start test, were used to assess
      what was learned in this procedure. Results from both experiments indicated that
      tamarins acquired more information from an implicit chain than was required by
      the contingencies of reinforcement. These results contribute to the developing
      literature on nonhuman analogs of implicit learning.

PMID- 20140695
TI  - Pattern electroretinogram changes after intravitreal bevacizumab injection for
      diabetic macular edema.
AB  - We aimed at investigating the efficacy of intravitreal bevacizumab injection by
      evaluation of pattern electroretinogram (PERG) in diabetic patients with
      clinically significant macular edema (CSME). Thirty-five eyes of 35 patients with
      diabetes were treated with 2.5 mg of intravitreal bevacizumab injection as the
      primary therapy for CSME. The main outcome measures included best-corrected
      visual acuity, fundus fluorescein angiography, and P(50) amplitudes of pattern
      electroretinogram (PERG) before and after intravitreal injection. Mean visual
      acuity improved significantly from a mean LogMAR value of 1.1 +/- 0.2 at baseline
      to a maximum of 0.7 +/- 0.3 after a mean follow-up time of 6.4 months. The mean
      baseline P(50) and N(95) amplitudes of PERG before intravitreal injection were
      1.4 +/- 0.7 and 2.4 +/- 0.8 microV, respectively. After the treatment, the mean
      P(50) amplitude of PERG was 2.4 +/- 0.9 microV at 1-month, 2.3 +/- 0.8 microV at
      3-month, and 2.2 +/- 0.8 microV at the last visit, and the mean N(95) amplitude
      of PERG was 3.4 +/- 1.05 microV at 1-month, 3.3 +/- 0.9 microV at 3-month, and
      3.2 +/- 0.9 microV at the last visit, and the mean P(50) and N(95) amplitudes
      were significantly higher when compared with baseline values (for each, P <
      .001). Mild anterior chamber inflammation in four eyes was controlled with
      topical corticosteroids. Eyes with diabetic macular edema treated with
      intravitreal bevacizumab showed improvement in visual acuity that was accompanied
      by improvement in PERG amplitudes. Further randomized trials are needed to
      investigate the role of PERG measurements in the evaluation of the efficacy of
      intravitreal bevacizumab injection.

PMID- 20140696
TI  - Optimal control and sensitivity analysis of an influenza model with treatment and
      vaccination.
AB  - We formulate and analyze the dynamics of an influenza pandemic model with
      vaccination and treatment using two preventive scenarios: increase and decrease
      in vaccine uptake. Due to the seasonality of the influenza pandemic, the dynamics
      is studied in a finite time interval. We focus primarily on controlling the
      disease with a possible minimal cost and side effects using control theory which
      is therefore applied via the Pontryagin's maximum principle, and it is observed
      that full treatment effort should be given while increasing vaccination at the
      onset of the outbreak. Next, sensitivity analysis and simulations (using the
      fourth order Runge-Kutta scheme) are carried out in order to determine the
      relative importance of different factors responsible for disease transmission and
      prevalence. The most sensitive parameter of the various reproductive numbers
      apart from the death rate is the inflow rate, while the proportion of new
      recruits and the vaccine efficacy are the most sensitive parameters for the
      endemic equilibrium point.

PMID- 20140694
TI  - Association between serum amyloid A and obesity: a meta-analysis and systematic
      review.
AB  - BACKGROUND: Emerging evidence indicates an association of the acute-phase protein
      serum amyloid A (SAA) with obesity. Here we review and summarize quantitatively
      the available data related to this association. METHODS: PubMed was
      systematically searched using the terms "serum amyloid A" and "obesity." Eighty
      one relevant studies between January 1966 and July 2009 were identified. Of
      these, only 11 cross-sectional studies and 10 prospective studies with successful
      interventions met our inclusion criteria for the meta-analysis. All analyses were
      conducted using the Comprehensive Meta-Analysis software. Literature pertaining
      to the relationship between SAA and other inflammatory markers, and the
      association between SAA and obesity-related disorders, such as cardiovascular
      diseases, atherosclerosis, diabetes, and insulin resistance was also reviewed.
      RESULTS: A strong association between body mass index and SAA levels was found in
      the 11 cross-sectional studies. The overall correlation coefficient is 0.230 (95%
      CI 0.160-0.297, P < 0.0005). The ten prospective studies were subsequently
      analyzed, and the difference in SAA levels before and after weight loss,
      expressed as standardized mean difference was -0.480 (95% CI -0.678 to -0.283, P
      < 0.0005). We discuss some potential underlying mechanisms and clinical
      applications for reducing SAA levels in obesity.

PMID- 20140697
TI  - Statistical medium optimization and biodegradative capacity of Ralstonia eutropha
      toward p-nitrophenol.
AB  - The effect of p-nitrophenol (PNP) concentration with or without glucose and yeast
      extract on the growth and biodegradative capacity of Ralstonia eutropha was
      examined. The chemical constituents of the culture medium were modeled using a
      response surface methodology. The experiments were performed according to the
      central composite design arrangement considering PNP, glucose and yeast extract
      as the selected variables whose influences on the degradation was evaluated
      (shaking in reciprocal mode, temperature of 30 degrees C, pH 7 and test time of
      about 9 h). Quadratic polynomial regression equations were used to quantitatively
      explain variations between and within the models (responses: the biodegradation
      capacity and the biomass formation). The coefficient of determination was high
      (R(adjusted)(2) = 0.9783), indicating the constructed polynomial model for PNP
      biodegradative capacity explains the variation between the regressors fairly
      well. A PNP removal efficiency of 74.5% occurred within 9 h (15 mg/L as the
      initial concentration of PNP with use of yeast extract at 0.5 g/L).

PMID- 20140698
TI  - Synthesis of PVP-coated ultra-small Fe3O4 nanoparticles as a MRI contrast agent.
AB  - Ultra-small Fe(3)O(4) nanoparticles were prepared by using the coprecipitation
      method, in which the polyvinylpyrrolidone (PVP) serves as a stabilizer. The
      nanoparticles were characterized by means of X-ray diffraction (XRD),
      transmission electron microscopy (TEM), infra spectrum (IR), X-ray photoelectron
      spectroscopy (XPS) and in vivo magnetic resonance imaging (MRI) test. The results
      showed that the particles' size was determined by the dripping rate and that PVP
      molecules played the role of preventing the aggregation and restricting the size
      of Fe(3)O(4) nanoparticles. The Fe(3)O(4) nanoparticles with diameter from 6.5 to
      1.9 nm obviously exhibited negative contrast enhancement and concentrated at the
      target area guided by a permanent magnet.

PMID- 20140699
TI  - Biocompatibility of individually designed scaffolds with human periosteum for use
      in tissue engineering.
AB  - The aim of this study was to evaluate and compare the biocompatibility of
      computer-assisted designed (CAD) synthetic hydroxyapatite (HA) and
      tricalciumphosphate (TCP) blocks and natural bovine hydroxyapatite blocks for
      augmentations and endocultivation by supporting and promoting the proliferation
      of human periosteal cells. Human periosteum cells were cultured using an
      osteogenic medium consisting of Dulbecco's modified Eagle medium supplemented
      with fetal calf serum, Penicillin, Streptomycin and ascorbic acid at 37 degrees C
      with 5% CO(2). Three scaffolds were tested: 3D-printed HA, 3D-printed TCP and
      bovine HA. Cell vitality was assessed by Fluorescein Diacetate (FDA) and
      Propidium Iodide (PI) staining, biocompatibility with LDH, MTT, WST and BrdU
      tests, and scanning electron microscopy. Data were analyzed with ANOVAs. RESULTS:
      After 24 h all samples showed viable periosteal cells, mixed with some dead cells
      for the bovine HA group and very few dead cells for the printed HA and TCP
      groups. The biocompatibility tests revealed that proliferation on all scaffolds
      after treatment with eluate was sometimes even higher than controls. Scanning
      electron microscopy showed that periosteal cells formed layers covering the
      surfaces of all scaffolds 7 days after seeding. CONCLUSION: It can be concluded
      from our data that the tested materials are biocompatible for periosteal cells
      and thus can be used as scaffolds to augment bone using tissue engineering
      methods.

PMID- 20140700
TI  - Glial cells are involved in the exciting effects of doxapram on brainstem slices
      in vitro.
AB  - This study tested whether the glial cells are involved in the exciting effects of
      doxapram on brainstem slice in vitro. Experiments were performed in brainstem
      slice preparations from neonatal rats. The medial area of nucleus retrofacialis
      (mNRF) and the hypoglossal nerve (XII nerve) were contained in the preparations.
      The slices were perfused with modified Kreb's solution (MKS), and the rhythmical
      respiratory discharge activity (RRDA) was simultaneously recorded from the XII
      nerve by using suction electrodes, including the discharge time course of
      inspiratory (Ti), expiratory (Te), respiratory cycle (RC), and integrity
      amplitude of inspiratory discharge (IA). After applying of doxapram (5 microM) to
      the MKS for 10 min, Ti and IA increased significantly (85.0 +/- 25.0%, 13.2 +/-
      2.5%, respectively, P < 0.05), the Te and the RC decreased significantly (19.0 +/
      1.4%, 12.8 +/- 1.4%, respectively, P < 0.05) when compared with control group.
      When the methionine sulfoximine (MS, 10 microM), a blockage of glutamine
      synthetase, was applied, all the exciting effects of doxapram on RRDA were
      reversed. After the glutamine (20 microM) was applied to the MKS for 10 min, the
      exciting effects were revealed again. Our results suggest that the normal
      metabolism of glial cells takes a key role in the modification of the RRDA in the
      slices. In conclusion, glial cells are involved in the exciting effects of
      doxapram on brainstem slice in vitro.

PMID- 20140701
TI  - Genetic variants on chromosome 5p12 are associated with risk of breast cancer in
      African American women: the Black Women's Health Study.
AB  - Two single nucleotide polymorphisms (SNPs), rs4415084, and rs10941679 on
      chromosome 5p12 were associated with risk of breast cancer in a recent genome
      wide association study (GWAS) of women of European ancestry. Both SNPs are
      located in a large high-LD region and the causal variant(s) are still unknown. We
      conducted a nested case-control study in a cohort of African American women to
      replicate and narrow the region carrying the causal variant(s). We evaluated 14
      tagging SNPs in a 98 kb LD block surrounding the index SNPs in 886 breast cancer
      cases and 1,089 controls from the Black Women's Health Study. We used the Cochran
      Armitage trend test to assess association with breast cancer risk. Odds ratios
      were derived from logistic regression analyses adjusted for potential confounders
      including percent European admixture. We confirmed the reported association of
      rs4415084 SNP with overall risk of breast cancer (P = 0.06), and, as in the
      original study, observed a stronger association with estrogen receptor positive
      tumors (P = 0.03). We identified four other SNPs (rs6451770, rs12515012,
      rs13156930, and rs16901937) associated with risk of breast cancer at the nominal
      alpha value of 0.05; all of them were located in a 59 kb HapMap YRI LD block.
      After correction for multiple testing, the association with SNP rs16901937
      remained significant (P permutated = 0.038). The G allele was associated with a
      21% increased risk of breast cancer overall and with a 32% increase in tumors
      positive for both estrogen and progesterone receptors. The present results from
      an African ancestry (AA) population confirm the presence of breast cancer
      susceptibility genetic variants in the chromosome 5p12 region. We successfully
      used the shorter range of LD in our AA sample to refine the localization of the
      putative causal variant.

PMID- 20140702
TI  - Past recreational physical activity, body size, and all-cause mortality following
      breast cancer diagnosis: results from the Breast Cancer Family Registry.
AB  - Few studies have considered the joint association of body mass index (BMI) and
      physical activity, two modifiable factors, with all-cause mortality after breast
      cancer diagnosis. Women diagnosed with invasive breast cancer (n = 4,153) between
      1991 and 2000 were enrolled in the Breast Cancer Family Registry through
      population-based sampling in Northern California, USA; Ontario, Canada; and
      Melbourne and Sydney, Australia. During a median follow-up of 7.8 years, 725
      deaths occurred. Baseline questionnaires assessed moderate and vigorous
      recreational physical activity and BMI prior to diagnosis. Associations with all
      cause mortality were assessed using Cox proportional hazards regression,
      adjusting for established prognostic factors. Compared with no physical activity,
      any recreational activity during the 3 years prior to diagnosis was associated
      with a 34% lower risk of death [hazard ratio (HR) = 0.66, 95% confidence interval
      (CI): 0.51-0.85] for women with estrogen receptor (ER)-positive tumors, but not
      those with ER-negative tumors; this association did not appear to differ by
      race/ethnicity or BMI. Lifetime physical activity was not associated with all
      cause mortality. BMI was positively associated with all-cause mortality for women
      diagnosed at age > or =50 years with ER-positive tumors (compared with normal
      weight women, HR for overweight = 1.39, 95% CI: 0.90-2.15; HR for obese = 1.77,
      95% CI: 1.11-2.82). BMI associations did not appear to differ by race/ethnicity.
      Our findings suggest that physical activity and BMI exert independent effects on
      overall mortality after breast cancer.

PMID- 20140703
TI  - The use of FDG-PET in assessing axillary lymph node status in breast cancer: a
      systematic review and meta-analysis of the literature.
AB  - Axillary lymph node status is the most powerful prognostic indicator in patients
      with breast cancer. FDG-PET has been suggested as a non-invasive method of
      staging the axilla. The aim of this study was to review and aggregate all studies
      that measured the performance of FDG-PET in patients with breast cancer, using
      surgically obtained axillary histology as a reference, in a meta-analysis. A
      systematic review of the literature was performed and data extracted from all
      eligible studies. These were then analysed using meta-analysis software and
      summary receiver operating characteristic (SROC) curves were plotted for the
      aggregate data. The data was then tested to determine which parameters impacted
      on the sensitivity and specificity of the studies. Sensitivities ranging from 20
      to 100% and specificities ranging from 65 to 100% have been reported. An
      aggregated ROC analysis found an area under the curve of 0.95 (95% CI 0.91-0.97)
      and a Q* value of 0.89 (95% CI 0.85-0.92) in a total of 25 studies involving
      2,460 patients. The AUC and Q* values indicated little difference between the
      compared study characteristics. The performance of the technique currently
      remains below, which is required to replace assessment of axillary node status by
      surgical biopsy and histological assessment. However, sensitivity and specificity
      are high and FDG-PET may have a role to play under particular circumstances.
      Moreover, the additional benefit of an assessment of distal metastatic spread
      provided by FDG-PET requires further investigation.

PMID- 20140704
TI  - ICG fluorescence-guided sentinel node biopsy for axillary nodal staging in breast
      cancer.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy is a selective approach to axillary
      staging of breast cancer with reduced morbidity. Current detection methods
      including radioisotope and blue dye show good results but some drawbacks are
      remaining. Indocyanine green (ICG) fluorescence detection was evaluated as a new
      method for SLN biopsy in breast cancer allowing both transcutaneous visualization
      of lymphatic vessels and intraoperative identification of SLN. METHODS: Forty
      three women with clinically node negative breast cancer received subareolar
      injection of ICG for fluorescence detection of SLN. All patients underwent either
      planned axillary lymph node dissection (ALND) with SLN biopsy or selective SLN
      biopsy to determine need for ALND. Clinical feasibility, detection rate,
      sensitivity, and axillary recurrence after isolated SLN biopsy were analyzed.
      RESULTS: Overall ICG fluorescence imaging identified 2.0 SLN in average in 42 of
      43 patients (detection rate: 97.7%). Metastatic involvement of the SLN was found
      in 17 of 18 nodal positive patients by conventional histopathology (sensitivity:
      94.4%). Immunohistochemistry revealed isolated tumor cells in five further cases.
      There was only one false-negative case in 43 patients (5.6%). In 17 of 23 overall
      nodal positive patients, the SLN was the only positive lymph node. After a median
      follow-up of 4.7 years none of the patients presented with axillary recurrence.
      CONCLUSION: ICG fluorescence imaging is a new method for SLN biopsy in breast
      cancer with acceptable sensitivity and specificity comparable to conventional
      methods. One advantage of this technique is that it allows transcutaneous
      visualization of lymphatic vessels and intraoperative lymph node detection
      without radioisotope.

PMID- 20140705
TI  - Drug treatments in a neonatal setting: focus on the off-label use in the first
      month of life.
AB  - OBJECTIVE: The purpose of this work was to analyse drugs prescribed in the first
      month of life among a group of newborns admitted to the Neonatal Intensive Care
      Unit and Neonatal Pathology of Cagliari University Hospital. METHOD: This pilot
      study was prospectively conducted during a 1-month period and involved all
      newborns admitted to our hospital that received a pharmacotherapy. After
      obtaining written parental consent, data collected from each newborn included
      date of birth, sex, gestational age and weight. Also, diagnosis and information
      about each drug administered during the first month of life: dose, frequency,
      route of administration, and indication for use was collected. RESULTS: Among the
      79 newborn infants admitted to our hospital during the study period, 38 received
      a pharmacotherapy and were enrolled in our study. A total of 88 treatments were
      given: 41 (47%) followed the terms of the product license, 47 (53%) were used in
      an unlicensed or off-label manner. CONCLUSION: Our results confirm this trend of
      drug use in the neonatological field and suggest the need to update information
      contained in the data sheets of medicines.

PMID- 20140706
TI  - Characterization of microRNAs from sheep (Ovis aries) using computational and
      experimental analyses.
AB  - Ovis aries is one of the most important agricultural livestock for meat
      production, and also is an ideal model organism for biological and comparative
      genomics studies. Many miRNAs have been reported for their important roles in
      developmental processes in various animals, but there is limited information
      about O. aries miRNAs. In this study, combining a computational method based on
      expressed sequence tag (EST) analysis with experimental identification based on
      small RNA cDNA library, we identified 31 miRNAs belong to 24 families in sheep, 2
      of which were novel miRNAs which had never been previously identified in any
      species. Especially, we cloned 12 miRNAs from the sheep skeletal muscle, which
      were good candidate miRNAs to be studied about the miRNA-dependant regulated
      process of muscle development, and we identified four pairs of miRNA/miRNA and
      one pair of miRNA-3p/miRNA-5p from sheep EST sequences. Expression analysis
      indicated that some miRNAs were expressed in a specific tissue, and the pair of
      miRNA-3p/miRNA-5p and one pair of miRNA/miRNA had a similar relative expression
      pattern in some tissues, respectively. Further, we predicted 120 potential target
      genes of 31 oar-miRNAs on the 3'UTR of O. aries genes. Gene ontology analysis
      showed that most of these genes took part in the cellular process and metabolic
      process. Our results enriched the O. aries miRNA database and provided useful
      information for investigating biological functions of miRNAs and miRNA in sheep.

PMID- 20140707
TI  - Polymorphisms in the bovine ghrelin precursor (GHRL) and Syndecan-1 (SDC1) genes
      that are associated with growth traits in cattle.
AB  - Transgenically expressed Syndecan-1 was found in the hypothalamic nuclei that
      control energy balance, and was associated with maturity-onset obesity, while
      ghrelin has been shown to play important roles in the control of food intake,
      gastric acid secretion, energy homeostasis, and glucose and lipid metabolism.
      However, the roles of genetic variations of Syndecan-1 and ghrelin on growth
      trait have few been reported in cattle. Herein, five Chinese cattle breeds were
      analyzed by PCR-SSCP and DNA sequencing methods. The bovine ghrelin gene showed
      eleven SNPs g.[267G>A, 271G>A, 290C>T, 326A>G, 327T>C, 420C>A, 569A>G, 945C>T,
      993C>T, 4491A>G, 4644G>A] and three SNPs g.[420C>A, 569 A>G, 945C>T] were firstly
      detected in cattle. The bovine Syndecan-1 gene showed two SNPs. One SNP showed a
      transition C>G at position 21514, resulting in a synonymous mutation
      p.G(GGC)169G(GGG) and another showed a transversion C>T at position 22591,
      resulting in a synonymous mutation p.D(GAC)283D(GAT). In ghrelin gene, no
      significant associations were revealed between any variant sites and body weight,
      average daily gain, body sizes for different growth periods (6, 12, 18, and 24
      months old), as well as for the milk yield at 305 days, milk protein rate and
      milk fat percentage. However, the polymorphism of Syndecan-1 gene was
      significantly associated with bovine birth weight and body length. Hence, we
      first suggested that Syndecan-1 gene could be regarded as molecular marker for
      superior birth weight and body length.

PMID- 20140708
TI  - Molecular characterization and polymorphisms of the caprine Somatostatin (SST)
      and SST Receptor 1 (SSTR1) genes that are linked with growth traits.
AB  - Somatostatin (SST) and its receptors (SSTR1-5) appear to be important in central
      regulation of many metabolic systems that affect growth, adiposity and nutrient
      absorption. In this study, we investigated polymorphisms within the caprine SST
      and SSTR1 genes and determined their relationship with growth traits. As there
      were no sequence information of the caprine SST and SSTR1 genes, we explored
      their DNA sequence and genomic organizations. The caprine SST gene is organized
      in two exons and is transcribed into an mRNA containing 351 bp of sequence coding
      for a protein of 116 amino acids. Its protein sequences showed substantial
      similarity (97-99%) to its respective orthologs from cattle, human and mouse. We
      also cloned and sequenced a 1.2 kb DNA fragment which contained the major part of
      the coding region and 3' UTR of the caprine SSTR1 gene. We then detected the
      polymorphisms in these determined sequences by PCR-SSCP and DNA sequencing
      methods in 459 goats from four breeds. Four SNPs (GU014693:g.647T>C,
      GU014693:g.844A>C, GU014693:g.970T>C, GU014693:g.1039T>A), segregating as two
      haplotypes (T-A-T-T and C-C-C-A), were identified in intron 1 of the caprine SST
      gene and showed the associations to body length and body height (P < 0.05). Two
      SNPs (GU014695:g.801 C>T, GU014695:g.948 C>T) were identified in the caprine
      SSTR1 gene. Significant associations between the three genotypes of GU014695:801
      C>T and body length, body height, and chest circumference was observed (P <
      0.05). These results suggest that the caprine SST and SSTR1 genes are strong
      candidate genes that influence growth traits in goat.

PMID- 20140709
TI  - Characterization of an ADP-glucose pyrophosphorylase small subunit gene expressed
      in developing cotton (Gossypium hirsutum) fibers.
AB  - ADP-glucose pyrophosphorylase (ADPGp, EC 2.7.7.27) is a tetrameric protein
      composed of two small and two large subunits that catalyzes the biosynthesis of
      ADP-glucose from glucose-phosphate which is used to provide the glucose subunits
      for starch biosynthesis. A second cotton gene encoding an ADPGp small subunit has
      been cloned and characterized. The gene contains eight introns similar to
      previously reported potato and cotton ADPGp small subunit genes. The deduced
      translation of the gene contained a poorly conserved transit peptide and well
      conserved catalytic and regulatory elements typical of other plant ADPGps. The 5'
      end of the mRNA was cloned and sequenced to identify the transcriptional start
      site (TSS). The promoter region upstream of the TSS did not contain the core
      promoter sequence in the typical positions indicating this gene may not use a
      standard core promoter. Other sequence motifs associated with tissue specific
      expression and phytohormone response were present. Reverse transcription (RT)-PCR
      with gene specific primers identified the sites of expression of this gene.
      Expression was most abundant in the meristem region, and immature stem and
      relatively lower in starch accumulating roots demonstrating that this gene has a
      different pattern of expression than the previously reported cotton ADPGp small
      subunit gene. Additionally this gene was differentially expressed in cotton
      fibers. The presence of starch was confirmed in developing cotton fibers
      suggesting that starch metabolism plays a role in cotton fiber development.

PMID- 20140710
TI  - Two novel SNPs of the ABCG2 gene and its associations with milk traits in Chinese
      Holsteins.
AB  - The ATP-binding cassette transporter ABCG2 (also known as breast cancer
      resistance protein, BCRP) belongs to the ATP-binding cassette (ABC) family of
      transmembrane drug transporters, playing a crucial role in the protection of
      various cells and tissues against xenotoxins and/or endotoxins. Recently, several
      studies have proposed it as the potential gene underlying the QTL on bovine
      chromosome 6. Hence, in this study, the PCR-SSCP method was applied to detect two
      polymorphisms (A -> C and A -> G) in the target sequence coding nucleotide
      binding domain (NBD) region of ABCG2 and evaluate its associations with milk
      production traits and mastitis-related traits among Chinese Holsteins. In the
      analyzed population, the allelic frequencies for the A and B alleles were 0.5990
      and 0.4010, respectively and the genotypic frequencies were in Hardy-Weinberg
      disequilibrium (P < 0.01). Moreover, significant statistical relationships
      between the polymorphisms of ABCG2 gene and following traits, including milk
      yields, milk protein percentage and somatic cell scores (SCS), were found (P <
      0.05). When compared with AA genotype, BB genotype was associated with higher
      milk yields during 1st and 2nd lactations, as well as lower milk protein
      percentage and SCS. Thus, BB genotype is suggested to be a molecular marker for
      superior milk performance.

PMID- 20140711
TI  - Whole effluent assessment of industrial wastewater for determination of bat
      compliance: Part 1: Paper manufacturing industry.
AB  - BACKGROUND, AIM AND SCOPE: The applicability of the Whole Effluent Assessment
      concept for the proof of compliance with the "best available techniques" has been
      analysed with paper mill wastewater from Germany by considering its persistency
      (P), potentially bio-accumulative substances (B) and toxicity (T). MATERIALS AND
      METHODS: Twenty wastewater samples from 13 paper mills using different types of
      cellulose fibres as raw materials have been tested in DIN or ISO standardised
      bioassays: the algae, daphnia, luminescent bacteria, duckweed (Lemna), fish-egg
      and umu tests with lowest ineffective dilution (LID) as test result. The
      potentially bio-accumulative substances (PBS) were determined by solid-phase
      microextraction and referred to the reference compound 2,3-dimethylnaphthalene.
      Usually, a primary chemical-physical treatment of the wastewater was followed by
      a single or multi-stage biological treatment. One indirectly discharged
      wastewater sample was pre-treated biologically in the Zahn-Wellens test before
      determining its ecotoxicity. RESULTS: No toxicity or genotoxicity at all was
      detected in the acute daphnia and fish egg as well as the umu assay. In the
      luminescent bacteria test, moderate toxicity (up to LIDlb=6) was observed.
      Wastewater of four paper mills demonstrated elevated or high algae toxicity (up
      to LIDA=128), which was in line with the results of the Lemna test, which mostly
      was less sensitive than the algae test (up to LIDDW=8). One indirectly discharged
      wastewater sample was biodegraded in the Zahn-Wellens test by 96% and was not
      toxic after this treatment. Low levels of PBS have been detected (median 3.27
      mmol L(-1)). The colouration of the wastewater samples in the visible band did
      not correlate with algae toxicity and thus is not considered as its primary
      origin. Further analysis with a partial wastewater stream from thermomechanically
      produced groundwood pulp (TMP) revealed no algae or luminescent bacteria toxicity
      after pre-treatment of the sample in the Zahn-Wellens test (chemical oxygen
      demand elimination 85% in 7 days). Thus, the algae toxicity of the respective
      paper mill cannot be explained with the TMP partial stream; presumably other raw
      materials such as biocides might be the source of algae toxicity. DISCUSSION:
      Comparative data from wastewater surveillance of authorities confirmed the range
      of ecotoxicity observed in the study. Wastewater from paper mills generally has
      no or a moderate ecotoxicity (median LID 1 and 2) while the maximum LID values,
      especially for the algae and daphnia tests, are considerably elevated (LIDA up to
      128, LIDD up to 48). CONCLUSIONS: Wastewater from paper mills generally is low to
      moderately ecotoxic to aquatic organisms in acute toxicity tests. Some samples
      show effects in the chronic algae growth inhibition test which cannot be
      explained exclusively with colouration of the samples. The origin of elevated
      algae ecotoxicity could not be determined. In the algae test, often flat dose
      response relationships and growth promotion at higher dilution factors have been
      observed, indicating that several effects are overlapping. RECOMMENDATIONS AND
      PERSPECTIVES: At least one bioassay should be included in routine wastewater
      control of paper mills because the paper manufacturing industry is among the most
      water consuming. Although the algae test was the most sensitive test, it might
      not be the most appropriate test because of the complex relationship of
      colouration and inhibition and the smooth dose-effect relationship or even
      promotion of algae growth often observed. The Lemna test would be a suitable
      method which also detects inhibitors of photosynthesis and is not disturbed by
      wastewater colouration.

PMID- 20140712
TI  - Electron transfer in Paracoccus denitrificans with the modified fbc operon.
AB  - Membrane fragments of two mutant strains of Paracoccus denitrificans genetically
      modified in the bc(1) complex have been studied for comparison of enzymic
      activities of succinate-cytochrome-c reductase and its components, viz. succinate
      dehydrogenase (Complex II) and ubiquinol-cytochrome-c reductase (Complex III) and
      their response to changes in concentration of succinate, cytochrome c, ionic
      strength, pH, temperature and sensitivity to antimycin A. The mutants synthesized
      and assembled the b and c hemes in the ratio characteristic for the wild type
      strain. The mutant strain M 71 expressing the truncated copy of cytochrome c(1)
      (devoid of a stretch of 150 mainly acidic amino acids) was less sensitive to
      increasing concentration of cytochrome c and changes in ionic strength of the
      medium, but maintained the original affinity to succinate and sensitivity to
      antimycin A. The mutant strain M 36 with an overexpressed bc(1) content showed
      the highest response to changes in ionic strength and physical parameters,
      exhibited the lowest turnover number values with succinate-cytochrome-c
      reductase, but positively affected the succinate dehydrogenase. In view of the
      interaction of the redox components in native membranes the functional analyses
      of separated Complexes II and III should be regarded with caution.

PMID- 20140713
TI  - Isolation and characterization of a N,N'-dicyclohexylcarbodiimide-resistant
      mutant of Methanothermobacter thermautotrophicus with alterations to the ATP
      synthesis machinery.
AB  - A spontaneous mutant of Methanothermobacter thermautotrophicus resistant toward
      the ATP-synthase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD) was isolated.
      DCCD normally inhibits methanogenic electron-transport-driven ATP synthesis,
      however, the DCCD-resistant strain exhibited methanogenesis in the presence of
      300 micromol/L DCCD. Total ATP synthesis was shown to be higher in the mutant
      strain, both in the presence and absence of DCCD. These results suggested a
      modification in the ATP-synthesizing system of the mutant strain. Using Blue
      Native PAGE combined with MALDI TOF/TOF mass spectrometry, increased
      concentrations of both the A(1) and A(o) subcomplexes of the A(1)A(o)-type
      synthase were identified in the mutant strain. However, no alterations were found
      in the structural genes (atp) for the A(1)A(o) ATP synthase. The results imply
      that DCCD resistance is a consequence of increased A(1)A(o) ATP synthase
      expression, and suggest that genes involved in regulating synthase expression are
      responsible for DCCD resistance.

PMID- 20140714
TI  - Biochemical and molecular characterization of delta-endotoxins in Bacillus
      thuringiensis.
AB  - The delta-endotoxins (delta-ETX) of four native strains (RT7, RT19, RT25, and
      RT25), and one reference strain (4L1) of Bacillus thuringiensis were
      biochemically and molecularly characterized to determine their potential toxic
      activity against lepidopteran larvae. Crystals of delta-ETX were purified through
      a two-phase system to determine their morphology, molar mass, solubility, and
      resistance to proteinases. Toxic activity and cry gene content were also
      determined. Crystals from native strains exhibited polyhedral, irregular and
      cuboidal shapes, while those from 4L1 were bipyramidal. Seven proteins with
      estimated molar mass approximately 30-134 kDa were detected as the main
      components of the native delta-ETX. Only crystals from 4L1, RT24, and RT25
      underwent complete solubilization at pH >12.0. Crystals from all strains produced
      trypsin-resistant peptides. None of the cry genes associated with toxicity in
      lepidopterans (cry1, cry2, cry9) was found in the native strains; however, 4L1
      strain harbors cry1 and cry2 genes. Strains RT19 and RT25 caused significant
      mortality against Trichoplusia ni larvae with partial solubilization at pH 10,
      strain 4L1 caused 100 % mortality. Toxicity of native strains may come from a
      novel cry gene.

PMID- 20140715
TI  - Genotoxic activity of Eucalyptus globulus essential oil in Aspergillus nidulans
      diploid cells.
AB  - Eucalyptus globulus essential oil was evaluated for its genotoxic potential using
      a somatic segregation assay and a diploid strain of the fungus Aspergillus
      nidulans, heterozygous for nutritional and conidia color markers. The main
      compounds of the current essential oil sample were eucalyptol (49.0 %), alpha
      pinene (8.9), beta-pinene (1.5), globulol (6.9), alpha-eudesmol (1.12),
      spathulenol (1.42), gamma-cadinene (1.45), trans-beta-elemenone (1.23) and
      aromandendrene (2.3), totaling 74 % of oil. Oil at 0.12 and 0.25 microL/mL was
      found to increase the mitotic instability of the original diploid strain and the
      number of diploid mitotic recombinants of A. nidulans. The genotoxicity of the
      oil was associated with the induction of mitotic crossing-over or with oil-broken
      chromosomes.

PMID- 20140716
TI  - Extracellular enzyme production in Metarhizium anisopliae isolates.
AB  - Extracellular enzymes produced by Metarhizium anisopliae are believed to play a
      key role in cuticle hydrolysis. The in-vitro production of cuticle-degrading
      enzymes, such as chitinase, proteinase, caseinase, lipase and amylase in fourteen
      isolates of M. anisopliae exhibited significant natural isolate variability. The
      isolates were also evaluated for chitinase and proteinase enzyme assays in order
      to quantify the enzyme production. The growth characteristics and colony
      morphology of the isolates showed variation and few isolates formed sectors and
      the colonies were either fluffy or powdery. Among the isolates studied, isolate
      UM2 was found to show good consistence with the results on enzyme measurements as
      well as the growth characteristics and colony morphology. Such characterization
      of isolate variability could rationally be used in the selection of isolates for
      the production of improved myco-pesticides in the integrated pest management
      programs.

PMID- 20140717
TI  - Modulation of enzyme activities of a lead-adapted strain of Rhizopus arrhizus
      during bioaccumulation of lead.
AB  - Activity of some enzymes of a Pb-adapted strain of Rhizopus arrhizus augmented
      significantly during bioaccumulation of Pb from a chemically defined medium. The
      mycelium of a Pb-adapted strain exposed to 1 microg/mL Pb in a defined medium for
      10 d at 28 +/- 2 degrees C exhibited, relative to a wild-type strain, increased
      activities of antioxidant enzymes, i.e. SOD, CAT and GPX and of enzymes like AP
      and PPO involved in defense against pathogens. Another response is a significant
      increase in the cellular thiol content after 4 d. The responses to Pb exposure
      thus include an increase in the antioxidant and anti-pathogen defense, and an
      increased metal-chelating ability.

PMID- 20140718
TI  - Efficient biocatalytic production of D-4-hydroxyphenylglycine by whole cells of
      recombinant Ralstonia pickettii.
AB  - The first establishment of a homologous expression system in the host Ralstonia
      pickettii CGMCC1596 using the compatible broad-host-range plasmid pWB5 is
      described. When whole cells of the recombinant strain R. pickettii MMYY01
      (CGMCC1596/pYY05) were used as the biocatalyst to transform DL-4
      hydroxyphenylhydantoin (DL-HPH) to D-4-hydroxyphenylglycine (D-HPG), the
      conversion rate reached 94 % in first 9 h, at a production rate of 2.8 g L(-1) h(
      1), with the rapid reduction of the intermediate [N-carbamoyl-2-(4
      hydroxyphenyl)glycine], compared with 80 % in >50 h at a rate of 0.5 g L(-1) h(
      1) for the CGMCC1596. The stability of the recombinant plasmid pYY05 is
      sufficient for its application in industrial batch fermentation. An alternative
      strategy for the conversion of DL-HPH to D-HPG by resting CGMCC1596 cells and
      heterologous DCase expressed by E. coli is discussed.

PMID- 20140719
TI  - Susceptibility of Staphylococcus aureus strains toward combinations of oxacillin
      2,4-dihydroxychalcone.
AB  - In order to determine the existence of synergism of the bacteriostatic action of
      flavonoids against G(+) bacteria between a clinically interesting conventional
      antibiotic and a flavonoid, combinations of oxacillin (OXC) and 2,4
      dihydroxychalcone (DCH) as enhancer were assayed against methicillin-sensitive
      Staphylococcus aureus ATCC 29 213 and methicillin-resistant S. aureus ATCC 43
      300. Using a kinetic-turbidimetric method, growth kinetics was monitored in a
      broth containing variable amounts of OXC alone and combinations of variable OXC
      constant DCH. The minimum inhibitory concentrations (MIC) of OXC alone and in
      combination with DCH were evaluated. For the 29 213 strain, OXC MIC was 25
      microg/mL, while combinations of 2-8 microg/mL OXC with 10 microg/mL of DCH
      totally inhibited growth and showed synergism. The resistance of the 43 300
      strain in the presence of OXC was verified; OXC-DCH combinations decreased
      bacterial growth by 35 %. DCH augments the action of OXC against methicillin
      susceptible S. aureus and therefore constitutes a good bacteriostatic agent for
      methicillin-resistant S. aureus.

PMID- 20140720
TI  - The effects of thiamine inhibition on ruminal fermentation: a preliminary study.
AB  - Inhibition of methanogenesis in ruminal cultures was attempted by hindering
      thiamine availability through its degradation by 'polyphenols' and competition
      for active sites on enzymes and transporters using thiamine structural analogs.
      Effects on fermentation were small and not consistently reversed by adding
      thiamine. Lack of major effects of the compounds evaluated could be due to
      intracellular synthesis of thiamine covering most requirements.

PMID- 20140721
TI  - Comparison of nisin and monensin effects on ciliate and selected bacterial
      populations in artificial rumen.
AB  - The effect of daily supplementation of nisin (2 mg/L), monensin (5.88 mg/L) and
      nisin and monensin (2 + 5.88 mg/L) on ovine ruminal ciliates and bacteria was
      investigated using the artificial rumen RUSITEC. Major groups in RUSITEC were
      Entodinium spp. and Dasytricha ruminantium. The supplementation of nisin
      significantly increased the population of both major ciliate groups. The
      supplementation of monensin significantly decreased the population of both
      groups. The combined effect of nisin and monensin was similar to the effect of
      monensin. Monensin had strong antiprotozoic effects in contrast to the
      stimulatory effects of nisin. D. ruminantium followed by Entodinium spp. appeared
      more resistant to tested compounds than other rumen ciliates. Tested additives
      did not significantly influence the presence and growth of amylolytic
      streptococci and enterococci but nisin showed a tendency to decreasing the
      concentration of Escherichia coli and lactobacilli.

PMID- 20140722
TI  - Probiotic Lactobacillus strains: in vitro and in vivo studies.
AB  - Three Lactobacillus strains (LOCK 0900, LOCK 0908, LOCK 0919) out of twenty-four
      isolates were selected according to their antagonistic activity against
      pathogenic bacteria, resistance to low pH and milieu of bile salts. Intragastric
      administration of a mixture of these strains to Balb/c mice affected cytokine
      T(H)1-T(H)2 balance toward nonallergic T(H)1 response. Spleen cells, isolated
      from lactobacilli-treated mice and re-stimulated in vitro with the mixture of
      heat-inactivated tested strains, produced significantly higher amounts of anti
      allergic tumor necrosis factor- and interferon-gamma than control animals whereas
      the level of pro-allergic interleukin-5 was significantly lower. Lactobacillus
      cells did not translocate through the intestinal barrier into blood, liver and
      spleen; a few Lactobacillus cells found in mesenteric lymph nodes could create
      antigenic reservoir activating the immune system. The mixture of Lactobacillus
      LOCK 0900, LOCK 0908 and LOCK 0919 strains represents a probiotic bacterial
      preparation with possible use in prophylaxis and/or therapy of allergic diseases.

PMID- 20140723
TI  - Enterococci from piglets--probiotic properties and responsiveness to natural
      antibacterial substances.
AB  - Fifty-five strains of enterococci isolated from the piglet intestine were
      characterized in vitro for probiotic activity. Identification of the isolates
      revealed Enterococcus faecium as the predominant species (84 %). Forty strains
      (73 %) were found to produce bacteriocin-like substances (only into solid media)
      with activity almost only toward Gram-positive genera. Thirty-eight % of strains
      were resistant to tetracycline, 27 % to chloramphenicol, 18 % to erythromycin and
      16 % to vancomycin. In addition to control of strain safety, 6 % of isolates were
      beta-hemolytic and 16 % produced gelatinase. Seven strains selected for further
      probiotic assays exhibited sufficient survival rate at pH 3.0 after 3 h, in the
      presence of 1 % ox-bile and lysozyme after 1 d (over 107 CFU/mL in all tests).
      The adhesion of tested strains to porcine and human intestinal mucus was found in
      a similar range (1.4-14.0 % and 1.4-17.6 %, respectively). In accordance with
      current research effort to use and/or to combine various health promoting
      substances, the sensitivity of all isolates toward plant extracts and toward
      bacteriocins produced by animal and environmental strains was determined. All
      enterococci were sensitive toward oregano and sage extracts and toward one (E.
      faecium EF55--chicken isolate, activity of 25 600 AU/mL) of ten bacteriocin
      substances. It means that a similar anti-enterococcal potential of some
      bacteriocin substances may be observed as for certain plant extracts.

PMID- 20140724
TI  - Influence of selenium on innate immune response in kids.
AB  - The effect is described of selenium supplemented in an inorganic and organic form
      on the innate immune response of goats. Though the phagocytic activity (as a
      marker of the immune function) was found to be lower in organic-Se-treated group
      than in control (54.5 +/- 4.32 vs. 60.2 +/- 9.15 %), it did not generally exhibit
      any significant differences; similarly, no differences were found in the
      phagocytic index. The production of reactive oxygen species (ROS) was determined
      using the luminol-enhanced chemiluminescence (CL) (estimated as peak CL, integral
      CL and a peak time after addition of calcium ionophore A23187, opsonised zymosan
      (OZP) and phorbol-12-myristate-13-acetate as effectors. A significant ROS
      increase reflected in integral CL and a peak time was found in the inorganic-Se
      treated group when OZP was used as activator; other parameters did not exhibit
      significant changes. The supplementation of Se in inorganic form can thus be seen
      to influence positively the innate immune system of kids.

PMID- 20140725
TI  - Stimulation of protective and cross-protective immunity against influenza B virus
      after adjuvant mucosal immunization of mice.
AB  - Intratracheal immunization of mice with inactivated influenza B virus and
      delipidated Bacillus firmus as adjuvant increases protection of mice against
      infection with the homologous virus strain and induces cross-protection: mice
      immunized by influenza virus B/Yamanashi 166/98 were protected even against
      phylogenetically distant virus drift variant B/Lee/40 lethal for mice.

PMID- 20140726
TI  - Seroprevalence of Toxoplasma gondii antibodies in the Slovak Republic.
AB  - One-thousand eight-hundreds forty-five individuals were examined for the presence
      of Toxoplasma gondii antibodies, 31.3 % prevalence of them being found by using
      the complement fixation test as a screening method. The determined total
      antibodies were present mainly in low titers which show evidence of past or
      latent infection. The acute stage of toxoplasmosis by the detection of specific
      IgM and IgA was diagnosed. The occurrence of acute toxoplasmosis in the healthy
      population is very low and presents only at 0.3 %. There was no significant
      difference between genders (p = 0.232), but significant differences in the
      prevalence of toxoplasmosis depending on age (p < 0.001) and regions (p = 0.007)
      were found.

PMID- 20140727
TI  - Bacterial biofilms in patients with chronic rhinosinusitis.
AB  - The possible presence of biofilms was examined in mucosal specimens of 15
      patients, undergoing functional endoscopic sinus surgery or a modified Caldwell
      Luc approach for chronic rhinosinusitis (CRS). Biofilms were found in 7 of the 15
      patients, positive cultures being obtained in most samples, which supports the
      role of biofilms as an important factor in the pathogenesis of CRS.

PMID- 20140728
TI  - Two cases of severe invasive infections in children caused by Streptococcus
      pneumoniae serotype 14--case report.
AB  - Two cases are presented of severe pneumococcal infections in infants caused by
      serotype 14 Streptococcus pneumoniae. The first case--meningitis--caused by S.
      pneumoniae (pneumococcus) with low-level penicillin susceptibility has developed
      from acute otitis media and resulted in fatal outcome. The second one--an
      immunocompromised child presenting recurrent otitis and chronic mastoiditis-
      developed into pneumococcal pneumonia. Both cases demonstrate the extreme
      importance of a relevant initial treatment of localized pneumococcal infections,
      preventing the development of generalized infection. Amoxicillin (an oral
      treatment option in both upper and lower respiratory tract infections caused also
      by Pneumococcus strains with low-level penicillin susceptibility due to its
      beneficial pharmacokinetics and pharmacodynamics) was not used in either case.

PMID- 20140729
TI  - Cryptococcal meningitis--a follow-up study of a serious clinical entity: quick
      cytological and microbiological diagnostics using a special staining procedure in
      cerebrospinal fluid specimens.
AB  - A routine diagnostic procedure of cryptococcal meningitis using Alcian Blue and
      Nuclear Fast Red staining is described in a group of 16 patients. Cerebrospinal
      fluid findings, including clinical cytology, routine biochemistry and protein
      fractions, are presented.

PMID- 20140730
TI  - Phenethyl isocyanate is not the metabolite of phenethyl isothiocyanate
      responsible for mechanism-based inhibition of cytochrome P450.
AB  - Phenethyl isothiocyanate is a chemopreventive phytochemical present in
      cruciferous vegetables where it exists as the glucosinolate gluconasturtiin. It
      is a mechanism-based inhibitor of both rat and human cytochrome P450 enzymes. The
      principal objective of the present study was to ascertain whether phenethyl
      isocyanate, formed by the cytochrome P450-mediated oxidative desulphuration of
      phenethyl isothiocyanate, is the metabolite responsible for the mechanism-based
      inhibition. Phenethyl isothiocyanate, following incubation with Aroclor 1254
      induced rat liver microsomes in the presence of NADPH, markedly suppressed the
      CYP1A-mediated O-deethylation of ethoxyresorufin; extent of inhibition was
      directly related to the pre-incubation time and was antagonised by reduced
      glutathione. When human liver microsomes were used, the inhibitory effect of
      phenethyl isothiocyanate, which was once again related to the pre-incubation
      time, was even more pronounced. When the ability of phenethyl isothiocyanate and
      phenethyl isocyanate to directly inhibit the O-deethylation of ethoxyresorufin in
      rat microsomes was compared, the latter compound was only moderately more
      effective. In human microsomes, both compounds were equipotent. In phenobarbital
      induced lung microsomes, phenethyl isothiocyanate was a direct and potent
      inhibitor of the O-depentylation of pentoxyresorufin; pre-incubation of the
      isothiocyanate had no impact. Human precision-cut liver slices were more
      effective than rat slices in metabolising phenethyl isothiocyanate. Pre-treatment
      of rats, however, with phenobarbitone significantly enhanced the metabolism of
      isothiocyanate. It may be inferred from the present studies that: (a) phenethyl
      isocyanate is not the metabolite of phenethyl isothiocyanate responsible for its
      mechanism-based inhibition, and (b) CYP2B is an important catalyst of the
      metabolism of phenethyl isothiocyanate.

PMID- 20140731
TI  - Spreading epidural hematoma and deep subcutaneous edema: indirect MRI signs of
      posterior ligamentous complex injury in thoracolumbar burst fractures.
AB  - OBJECTIVES: The purpose of this study was to evaluate the diagnostic value of a
      spreading epidural hematoma (SEH) and deep subcutaneous edema (DSE) as indirect
      signs of posterior ligamentous complex (PLC) injuries on MR imaging of
      thoracolumbar burst fractures. MATERIALS AND METHODS: We retrospectively reviewed
      spinal MR images of 43 patients with thoracolumbar burst fractures: 17 patients
      with PLC injuries (study group) and 26 without PLC injuries (control group). An
      SEH was defined as a hemorrhagic infiltration into the anterior or posterior
      epidural space that spread along more than three vertebrae including the level of
      the fracture. A DSE was regarded as a fluid-like signal lesion in the deep
      subcutaneous layer of the back, and its epicenter was at the burst fracture
      level. The frequency of the SEH/DSE in the two groups was analyzed. In addition,
      the association between each sign and the degree of vertebral collapse, the
      severity of central canal compromise, and surgical decisions were analyzed.
      RESULTS: Magnetic resonance images showed an SEH in 20 out of 43 patients (46%)
      and a DSE in 17 (40%). The SEH and DSE were more commonly seen in the study group
      with PLC injuries (SEH, 15 out of 17 patients, 80%; DSE, 16 out of 17 patients,
      94%) than in the control group without PLC injuries (SEH, 5 out of 26, 19%; DSE,
      1 out of 26, 4%) (P <0.0001). The SEH and DSE were significantly associated with
      surgical management decisions (17 out of 20 patients with SEH, 85%, vs 8 out of
      the 23 without SEH, 35%, P =0.002; 15 out of 17 with DSE, 88%, vs 10 out of 26
      without DSE, 38%, P =0.002). The SEH and DSE did not correlate with the degree of
      vertebral collapse or the severity of central canal compromise. CONCLUSION: The
      SEH and DSE may be useful secondary MR signs of posterior ligamentous complex
      injury in thoracolumbar burst fractures.

PMID- 20140732
TI  - Rheumatoid wrist deformity and risk of extensor tendon rupture evaluated by 3DCT
      imaging.
AB  - OBJECTIVE: Extensor tendon rupture on the dorsum of the wrist is commonly seen in
      patients with rheumatoid arthritis (RA). It causes immediate dysfunction of the
      hand and surgical reconstruction is usually required. The purpose of this study
      was to clarify the risk of extensor tendon rupture by quantifying wrist deformity
      on three-dimensional computed tomography (3DCT) images. MATERIALS AND METHODS:
      Three-dimensional CT images of 108 wrists in 102 patients with RA and 38 wrists
      in 38 healthy volunteers were analyzed retrospectively. All of the rheumatoid
      wrists had caused persistent pain for more than 6 months despite ongoing medical
      treatment. Extensor tendon rupture was noted in 49 wrists in 47 patients, and no
      rupture was noted in 59 wrists in 56 patients. The dorsal subluxation ratio (DSR)
      of the ulnar head and the carpal supination angle (CSA) were measured utilizing a
      new technique. RESULTS: The average DSR and CSA in the rupture group (n = 49),
      the non-rupture group (n = 59), and the normal wrist group (n = 38) were 37%,
      19%, and 26%, and 15 degrees , 11 degrees , and 6 degrees respectively. The cut
      off values for extensor tendon rupture in the wrists of patients with RA were 32%
      (sensitivity; 70%, specificity; 75%) in the DSR, and 14 degrees (71%, 68%) in the
      CSA. CONCLUSION: By utilizing 3DCT imaging of the rheumatoid wrist, these
      parameters can help improve our ability to predict extensor tendon rupture.

PMID- 20140733
TI  - Pancreas divisum in pancreaticobiliary maljunction in children.
AB  - PURPOSE: Pancreaticobiliary maljunction (PBM) is defined as a congenital anomaly
      in which the main pancreatic and common bile ducts are joined outside the
      duodenal wall and forms the long common channel. Although PBM and pancreas
      divisum are congenital anomalies causing pancreatitides, distinct data about the
      incidence of pancreas divisum in pediatric PBM has not been reported to date. The
      present study was designed to reveal the incidence and clinical features of
      pancreas divisum in cases of PBM. METHODS: The configurations of pancreatic ducts
      of 78 pediatric cases of PBM were assessed by endoscopic retrograde
      cholangiopancreatography (ERCP) and/or intraoperative cholangiopancreatography.
      Additional cannulation of the minor papilla was performed when the entire length
      of the main pancreatic duct was not detected with cannulation of the major
      papilla alone. RESULTS: Clear pancreatography was obtained in 71 cases out of 78
      cases of PBM. Abnormal fusion of the pancreatic duct was detected in 1 case
      (1.4%) with complete pancreas divisum. This case was asymptomatic preoperatively
      and for 10 years postoperatively. CONCLUSION: Pancreas divisum exists in 1.4% of
      PBM. Although pancreas divisum is one of the pathogenesis of pancreatitis in PBM,
      is rarely associated with PBM and not always causes pancreatitis.

PMID- 20140734
TI  - Injection volumes of dextranomer/hyaluronic acid are increasing in the endoscopic
      management of vesicoureteral reflux.
AB  - PURPOSE: Dextranomer/hyaluronic acid (Deflux) has been increasingly used for the
      treatment of vesicoureteral reflux (VUR). Experience has shown that injecting
      more volume of material is necessary to achieve greater success. We evaluate
      trends in the number of vials being used to treat VUR using a multi-institutional
      database and data from patients treated at our own institution. METHODS: Children
      of age 0-19 years in the Pediatric Health Information System (PHIS) database from
      2003 to 2008 were extracted with a VUR diagnosis (ICD-9 593.7x) and subureteric
      injection procedure code (CPT 52327). We identified children with reflux treated
      with endoscopic injection at Seattle Children's Hospital from 2005 to 2008.
      Hospital trends of the number of vials used were evaluated using multivariate
      linear regression. RESULTS: From 2003 to 2008, we identified 4,078 endoscopic
      injection procedures in PHIS. There was a 33% increase in the average number of
      vials used per patient (p < 0.0001) with more than a threefold increase in the
      number of patients receiving three or more vials per procedure. All institutions
      increased the average vials used per patient with the most pronounced increase at
      the highest-volume centers. These trends were also present in the 186 children
      treated at our own institution. CONCLUSION: Over the study period there was an
      increase in the number of vials of dextranomer/hyaluronic acid being used per
      patient to treat children with VUR. This practice may improve success rates but
      will increase the cost of treatment due to the inherent expense of the material.

PMID- 20140735
TI  - LigaSure compared with ligatures and endoclips in experimental appendectomy: how
      safe is it?
AB  - PURPOSE: The present study aims to compare strength, healing, and inflammation of
      appendiceal stumps closed by LigaSure Precise (Valleylab, Boulder, CO, USA)
      device, ligatures using polyglactin 910 (Vicryl, Ethicon, Edinburgh, UK) and
      endoclips (Ligaclip ERCA, Ethicon, OH, USA), and operation time (OT) in
      experimental appendectomy. METHODS: Forty-eight Sprague-Dawley rats were divided
      into two (Group A and B). Each group was further subdivided into three subgroups
      (AS, AC, AL, BS, BC, BL) containing eight rats. Appendectomy was performed and
      stump was closed by ligatures in S, by endoclips in C and by LigaSure in L
      subgroups. OT was recorded. In Group A, cecum bursting pressures (BP) were
      determined instantly after the operation. In Group B, BP, histological
      evaluations, and measurements of collagen contents estimated by the tissue
      hydroxyproline (HPL) level were made on the seventh postoperative day.
      Statistical analyses were performed with Kruskal-Wallis test and Mann-Whitney U
      test. P value was considered significant at less than 0.05. RESULTS: BPs of
      subgroups were comparable on postoperative immediate period and day 7. HPLs and
      OTs were significantly better in L subgroups. BL had the least inflammation.
      CONCLUSION: Better healing, less inflammation, shorter OT, and equal strength
      achieved with LigaSure device comparing with polyglactin 910 ties and endoclips
      in experimental appendectomy is encouraging.

PMID- 20140736
TI  - A novel splice-acceptor site mutation in CDH3 gene in a consanguineous family
      exhibiting hypotrichosis with juvenile macular dystrophy.
AB  - Mutations in CDH3 gene, encoding P-cadherin, are responsible for hypotrichosis
      with juvenile macular dystrophy (HJMD), which is a rare autosomal recessive
      disorder. The HJMD is characterized by congenital sparse hair on scalp and
      progressive severe degenerative changes of the retinal macula which leads to
      variable degrees of blindness. The present study reports a large consanguineous
      Pakistani family with six individuals affected with HJMD. Genotyping using
      polymorphic microsatellite markers showed linkage of the family to CDH3 gene on
      chromosome 16q22.1. Sequence analysis of the CDH3 gene revealed a novel splice
      site mutation (c.IVS10-1 G -> A) in intron 10, which leads to skipping of exon 11
      and probably synthesizing a non-functional premature truncated protein.

PMID- 20140737
TI  - Correlation between beta-2-glycoprotein I gene polymorphism and anti-beta-2
      glycoprotein I antibodies in patients with multibacillary leprosy.
AB  - Antiphospholipid antibodies, such as anti-beta2-glycoprotein I (beta2GPI), are
      present in multibacillary leprosy (MB) patients; however, MB patients do not
      usually present with antiphospholipid antibody syndrome (APS), which is
      characterized by thromboembolic phenomena (TEP). Rare cases of TEP occur in
      leprosy patients, but the physiopathology of this condition remains unclear. In
      this case-control study, we examined whether single-nucleotide polymorphisms
      (SNPs) of the beta2GPI gene contributed to the risk of leprosy and APS co
      morbidity. SNPs Ser88Asn, Leu247Val, Cys306Gly and Trp316Ser were identified in
      113 Brazilian leprosy patients. Additionally, anti-beta2GPI antibodies and plasma
      concentrations of beta2GPI were quantified. The Ser88Asn, Cys306Gly and Trp316Ser
      SNPs were not risk factors for APS in leprosy. A higher frequency of Val/Val
      homozygosity was observed in leprosy patients compared to controls (36 vs. 5%; P
      < 0.001). Forty-two percent of MB and 17% of paucibacillary leprosy patients were
      positive for anti-beta2GPI IgM (P = 0.014). There was no correlation between SNP
      Ser88Asn or Cys306Gly and anti-beta2GPI antibody levels. In MB patients with
      positive anti-beta2GPI IgM, the frequency of Val/Val homozygosity was higher than
      in controls (32 vs. 15%; P = 0.042). The frequency of the mutant allele Ser316
      was higher in MB patients with positive rather than negative anti-beta2GPI IgM
      levels (6 vs. 0%; P = 0.040) and was greater than in the control group (6 vs. 1%;
      P = 0.034). The studied polymorphisms did not influence the plasma concentrations
      of beta2GPI. These results suggest that Leu247Val and Trp316Ser SNPs may
      represent genetic risk factors for anti-beta2GPI antibody production in MB
      patients.

PMID- 20140738
TI  - Apolipoprotein epsilon4 allele is associated with psoriasis severity: reply.

PMID- 20140739
TI  - A chemical screen for suppressors of the avrRpm1-RPM1-dependent hypersensitive
      cell death response in Arabidopsis thaliana.
AB  - Arabidopsis thaliana RPM1 encodes an intracellular immune sensor that conditions
      disease resistance to Pseudomonas syringae expressing the type III effector
      protein AvrRpm1. Conditional expression of this type III effector in a transgenic
      line carrying avrRpm1 under the control of a steroid-inducible promoter results
      in RPM1-dependent cell death that resembles the cell death response of the
      incompatible RPM1-avrRpm1 plant-bacterium interaction. This line was previously
      used in a genetic screen, which revealed two genes that likely function in the
      folding of pre-activation RPM1. We established a chemical screen for small
      molecules that suppress steroid-inducible and RPM1-avrRpm1-dependent cell death
      in Arabidopsis seedlings. Screening of a library comprising 6,800 compounds of
      natural origin identified two trichothecene-type mycotoxins, 4,15
      diacetoxyscirpenol (DAS) and neosolaniol (NEO), which are synthesized by Fusarium
      and other fungal species. However, protein blot analysis revealed that DAS and
      NEO inhibit AvrRpm1 synthesis rather than suppress RPM1-mediated responses. This
      inhibition of translational activity likely explains the survival of the
      seedlings under screening conditions. Likewise, flg22-induced defense responses
      are also impaired at the translational, but not the transcriptional, level by DAS
      or NEO. Unexpectedly, both compounds not only prevented AvrRpm1 synthesis, but
      rather caused an apparent hyper-accumulation of RPM1 and HSP70. The hyper
      accumulation phenotype is likely unrelated to the ribotoxic function of DAS and
      NEO and could be due to an inhibitory activity on the proteolytic machinery of
      Arabidopsis or elicitor-like activities of type A trichothecenes.

PMID- 20140740
TI  - Peripheral blood gene expression of B7 and CD28 family members associated with
      tumor progression and microscopic lymphovascular invasion in colon cancer
      patients.
AB  - PURPOSE: To associate the global gene expression of B7/CD28 family transcripts
      with pathologic features of colon cancer, we determined the B7/CD28 family
      transcripts in peripheral blood mononuclear cells (PBMCs) from normal subjects
      and patients with adenomatous polyps and colon cancer, and correlated the results
      with pathologic features of colon cancer. METHODS: PBMCs from age-matched normal
      subjects and patients with adenomatous polyps and colon cancer were analyzed for
      peripheral blood transcripts (PBTs) of B7/CD28 family using real-time PCR.
      Differences in expression levels of B7/CD28 PBTs across all cancer stages and
      between colon cancer patients with or without microscopic lymphovascular invasion
      (LVI) were analyzed. RESULTS: The results showed a significant upregulation of
      PBTs of co-inhibitory molecules such as B7-H3 and PD-1 and a significant PBT
      downregulation of co-stimulatory molecules including CD28 and ICOS in colon
      cancer patients. Furthermore, the increase of B7-H3 PBT was strongly associated
      with tumor invasion (P = 0.025) and advanced TNM stages (P = 0.019), whereas the
      decline of co-stimulatory ligand B7-H2 PBT was related to regional lymph node
      metastasis (P = 0.028) and aggressive tumor invasion (P = 0.031). In addition,
      the ratios of PBT expression of CD28 family to B7 family such as CTLA-4 to B7-H2
      and PD-1 to B7-H2 were significantly higher in colon cancer patients with
      microscopic LVI than in those without LVI (P = 0.001 and P = 0.016,
      respectively). CONCLUSIONS: Our results suggest that B7/CD28 family PBTs may
      serve as valuable markers reflecting the pathological features of colon cancer.

PMID- 20140741
TI  - Epigenetic alterations in disseminated neuroblastoma tumour cells: influence of
      TMS1 gene hypermethylation in relapse risk in NB patients.
AB  - PURPOSE: Most neuroblastoma patients over 18 months of age at diagnosis present
      disseminated disease. The presence of neuroblastoma cells in bone marrow can be
      used to evaluate the response to treatment. It is possible that alterations in
      certain tumour cells might confer a selective advantage over tumour dissemination
      process, and probably be helpful in the clonal selection of tumour-specific cells
      that could originate metastasis. METHODS: We performed real-time quantitative PCR
      to identify the presence of disseminated tumour cells in bone marrow samples, and
      we used MSP to analyse the methylation profile of 20 genes putatively implied in
      dissemination. RESULTS: We described epigenetic alterations in the methylated
      status of certain genes in disseminated tumour cells from bone marrow. Those
      cases with high rate of hypermethylation showed an increased probability of
      relapse during or after treatment. We found significantly poor prognosis in event
      free survival in cases with hypermethylation of TMS1, MGMT and RARbeta2 genes.
      CONCLUSION: We could not confirm the presence of a specific methylation profile
      in disseminated neuroblastoma tumour cells, but a high accumulation of epigenetic
      events in those cells is associated with a high risk of relapse, independently of
      MYCN amplification.

PMID- 20140742
TI  - Selective inhibition of human leukemia cell growth and induction of cell cycle
      arrest and apoptosis by pseudolaric acid B.
AB  - PURPOSE: The leukemias account for the largest number of cases of childhood
      cancer and remain the primary cause of cancer-related mortality among children in
      the United States. There is a need for novel antileukemia agents due to toxicity
      and resistant to existing chemotherapeutic agents. In this study, the effects of
      pseudolaric acid B (PAB) on three human leukemia cell lines, acute promyelocytic
      leukemia HL-60 cells, acute lymphoblastic leukemia CCRF-CEM cells, and human
      chronic myeloid leukemia blast-phase K562 cells were investigated in vitro,
      compared to normal human peripheral blood mononuclear cells (PBMC). METHODS: Cell
      viability was determined using CellTiter-Glo luminescent reagent. Colony
      formation was assessed by Microtitration cloning assay. Cell cycle analysis was
      carried out by flow cytometry. Tubulin polymerization was measured by recording
      the increase in absorbance. Inhibition of topoisomerase I (topo I) and
      topoisomerase II (topo II) enzyme activities was measured by DNA relaxation assay
      using topo I and II drug screening kit. Apoptosis was observed by DAPI staining
      assay and Caspase3/7 activities was measured using Caspase-Glo((R)) 3/7 assay
      kit. RESULTS: Pseudolaric acid B selectively inhibited the growth of human
      leukemia HL-60, CCRF-CEM and K562 cells, but not normal PBMC. PAB suppressed
      colony formation in HL-60 cells. Cell cycle analysis showed that PAB blocked the
      cell cycle at G(2)/M phase in HL-60 cells, suggesting that it suppresses mitosis.
      DNA topo I and topo II were not inhibited, but tubulin polymerization was
      inhibited. PAB-induced apoptosis and activated caspase-3/7 activity. CONCLUSIONS:
      This study indicates that PAB has a potential for use against leukemia and its
      effects might be mediated by inhibiting tubulin polymerization, preventing cell
      division and activating caspase-3, which leads to apoptosis.

PMID- 20140743
TI  - Suppression of human MDA-MB-435S tumor by U6 promoter-driven short hairpin RNAs
      targeting focal adhesion kinase.
AB  - PURPOSE: Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase
      implicated in cancer cell survival, proliferation, and in various steps in the
      metastatic cascade. In the present study, we took advantage of a cationic
      liposome as gene carrier and targeted FAK function through both in vitro and in
      vivo approaches. METHODS: We utilized a plasmid-encoded hairpin RNA targeting the
      human FAK mRNA (pGensil2-shRNA/FAK), as a means to inhibit FAK expression for
      evaluating its anti-tumor effect in vitro and in vivo. Human MDA-MB-435S breast
      cancer cells were transfected with pGensil2-shRNA/FAK and examined for apoptosis
      by propidium iodide staining, DNA ladder, and flow cytometric analysis. For in
      vivo study, subcutaneous breast carcinomatosis models in nude mice were
      established to evaluate the therapeutic potential of pGensil2-shRNA/FAK.
      Assessments of proliferation (Ki-67), apoptosis (TUNEL) and angiogenesis (CD31)
      were done using immunohistochemical analysis. RESULTS: Transcripts expressed from
      plasmid both in vitro and in vivo were identified by northern blot analysis.
      pGensil2-shRNA/FAK effectively down-regulated the expression of FAK as
      demonstrated in vitro by real time RT-PCR and western blot analysis, whereas by
      real time RT-PCR and IHC staining of MDA-MB-435S tumors growing subcutaneously.
      Breast cancer cells lacking FAK expression undergo apoptosis in vitro. Systemic
      delivery of cationic liposome-complexed plasmids targeting FAK, resulted in the
      diminishment of subcutaneous tumor growth beyond the effects observed with
      liposomes carrying a non-specific shRNA. This diminishment in growth was
      associated with elevated levels of apoptosis (TUNEL staining), decreased cell
      proliferation (Ki-67 staining) and diminished endothelial cell density (CD31
      staining). CONCLUSION: These results indicate that the systemic delivery of
      plasmid DNA targeting FAK function using cationic liposome as a gene carrier,
      represents a promising avenue for breast cancer therapy.

PMID- 20140744
TI  - Serum thymidine kinase 1 concentration as a prognostic factor of chemotherapy
      treated non-Hodgkin's lymphoma patients.
AB  - PURPOSE: This study was performed to examine possible use of thymidine kinase 1
      concentration in serum (STK1) for prognosis of non-Hodgkin's lymphoma patients
      following chemotherapy treatment. METHODS: The STK1 levels of 37 patients were
      determined by enhanced chemiluminescent dot-blot assay on the day before
      chemotherapy, and on day 1 and day 28 after start of the treatment. The
      specificity and sensitivity was evaluated by Western blot with anti-TK1 IgY
      antibody and by receiver operating characteristic (ROC) analysis. RESULTS:
      Western blot and ROC analysis of TK1 in serum showed high specificity and
      sensitivity. The mean STK1 level of the non-Hodgkin's lymphoma patients was
      significantly higher compared to healthy persons (p < 0.001). The mean STK1 level
      increased significantly (p < 0.001) on day 1 and then declined, reaching on day
      28 values corresponding to those of healthy persons. The mean STK1 values before
      treatment and at 1 and 28 days after start of the treatment also correlated
      significantly with the clinical response (CR, PR and NR) and five-year survival.
      CONCLUSION: Although the number of patients was limited in this study, TK1 in
      serum might possess an important reference value in the evaluation of treatment
      and prognosis of non-Hodgkin's lymphoma following chemotherapy.

PMID- 20140745
TI  - Percutaneous approach to the foramen ovale: an anatomical study of the
      extracranial trajectory with the incorrect trajectories to be avoided.
AB  - OBJECTIVE: Meckel's Cave may be accessed percutaneously through the foramen ovale
      (FO). Detailed knowledge of the region's anatomical surroundings is invaluable in
      improving target accuracy and preventing complications with this approach. The
      approach has been used in the treatment of trigeminal neuralgia as well as in
      performing biopsies of lesions located in the parasellar region, described
      formerly by the senior author (M.S.). A comprehensive cadaveric study of the
      region traversed by needle is thus presented. MATERIALS AND METHODS: Three
      cadaveric heads (six sides) were fixed in formaldehyde and injected with latex. A
      detailed description of the regional anatomical needle trajectories was
      performed. RESULTS: An "inverted pyramid" subdivided into three segments is
      described. The inferior third begins at cutaneous penetration and ends at the
      parotid duct (PD). The middle third extends from the PD to the lateral pterygoid
      muscle (LPM). The superior third starts from the LPM and ends at the FO. The main
      vascular anatomical variation was with regard to the maxillary artery (MA). In
      half of the cases, the MA traveled though the middle of the pyramid and in the
      other half through the upper third. CONCLUSIONS: Although widely used, the FO
      approach carries risks. Special attention is warranted when the needle traverses
      the upper third of the pyramid to avoid the variant course of the MA. Image
      guided techniques and detailed anatomical knowledge are necessary to expand the
      use of this route not just for approach to lesions within the parasellar and
      upper third of the petroclival region but also to lesions invading the
      infratemporal fossa.

PMID- 20140746
TI  - The perioperative use of oral anticoagulants during surgical procedures for
      carpal tunnel syndrome. A preliminary study.
AB  - BACKGROUND: To evaluate the feasibility of designing a randomized controlled
      study whether open carpal tunnel release (OCTR) surgery can be performed safely
      under systemic anticoagulant therapy using acetylsalicylacid (ASA) or
      acenocoumarol (ACM), this preliminary, observational study was performed.
      METHODS: Prospectively, during 1 year, data were collected from all patients who
      underwent conventional OCTR at the neurosurgical department of the Canisius
      Wilhelmina Hospital, Nijmegen, The Netherlands. Patients continued anticoagulant
      treatment perioperatively. RESULTS: A total of 364 patients were operated on, of
      whom 45 continued ASA and seven ACM treatment. Only one patient using ASA
      complained of a postoperative subcutaneous hemorrhage. In the control group
      without anticoagulants, none of the patients had a bleeding postoperatively.
      CONCLUSION: Continuation of anticoagulant treatment is safe for OCTR. The adverse
      effects of stopping treatment for surgery can be severe. As a result of this
      study, we have changed our surgery protocol for OCTR and continue anticoagulant
      treatment perioperatively.

PMID- 20140747
TI  - Apoptosis and apoptotic mimicry: the Leishmania connection.
AB  - Different death-styles have been described in unicellular organisms. In most
      cases they evolve with phenotypic features similar to apoptotic death of animal
      cells, such as phosphatidylserine (PS) exposure, oligonucleosomal DNA
      fragmentation, and loss of mitochondrial transmembrane potential, hinting that
      similar mechanisms operate in both situations. However, the biochemical pathways
      underlying death in unicellular organisms are still unclear. Host recognition of
      PS exposed on the surface of unicellular parasites is an important feature of the
      process of infection and progression of the disease. Here, we discuss data
      showing that entirely different mechanisms of PS exposure co-exist during the
      life-cycle of Leishmania amazonensis: in the case of promastigotes, a sub
      population dies by apoptosis; in the case of amastigotes, the entire population
      exposes PS, not necessarily followed by apoptotic death. This phenomenon has been
      called apoptotic mimicry. The elusive caspase-like activities described in
      protozoa are also discussed.

PMID- 20140748
TI  - Estrogen augments the T cell-dependent but not the T-independent immune response.
AB  - Estrogen plays a critical regulatory role in the development and maintenance of
      immunity. Its role in the regulation of antibody synthesis in vivo is still not
      completely clear. Here, we have compared the effect of estrogen on T cell
      dependent (TD) and T cell-independent type 2 (TI-2) antibody responses. The
      results provide the first evidence that estrogen enhances the TD but not the TI-2
      response. Ovariectomy significantly decreased, while estrogen re-administration
      increased the number of hapten-specific IgM- and IgG-producing cells in response
      to TD antigen. In vitro experiments also show that estrogen may have a direct
      impact on B and T cells by inducing rapid signaling events, such as Erk and AKT
      phosphorylation, cell-specific Ca(2+) signal, and NFkappaB activation. These non
      transcriptional effects are mediated by classical estrogen receptors and partly
      by an as yet unidentified plasma membrane estrogen receptor. Such receptor-
      mediated rapid signals may modulate the in vivo T cell-dependent immune response.

PMID- 20140751
TI  - Functional expression of Phanerochaete chrysosporium cellobiose dehydrogenase
      flavin domain in Escherichia coli.
AB  - Cellobiose dehydrogenase (CDH; EC 1.1.99.18) is an extracellular glycosylated
      protein composed of two distinct domains, a C-terminal catalytic flavin domain
      and an N-terminal cytochrome-b-type heme domain, which transfers electrons from
      the flavin domain to external electron acceptors. The soluble flavin domain of
      the Phanerochaete chrysosporium CDH was successfully expressed in Escherichia
      coli. The enzyme showed dye-mediated CDH activity higher than that of the
      complete CDH, composed of flavin domain and heme domain, prepared using Pichia
      pastoris as the host microorganism. The ability to conveniently express the
      recombinant CDH flavin domain in E. coli provides great opportunities for the
      molecular engineering of the catalytic properties of CDH.

PMID- 20140749
TI  - From carrot to clinic: an overview of the retinoic acid signaling pathway.
AB  - Vitamin A is essential for the formation and maintenance of many body tissues. It
      is also important for embryonic growth and development and can act as a teratogen
      at critical periods of development. Retinoic acid (RA) is the biologically active
      form of vitamin A and its signaling is mediated by the RA and retinoid X
      receptors. In addition to its role as an important molecule during development,
      RA has also been implicated in clinical applications, both as a potential anti
      tumor agent as well as for the treatment of skin diseases. This review presents
      an overview of how dietary retinoids are converted to RA, hence presenting the
      major players in RA metabolism and signaling, and highlights examples of
      treatment applications of retinoids. Moreover, we discuss the origin and
      diversification of the retinoid pathway, which are important factors for
      understanding the evolution of ligand-specificity among retinoid receptors.

PMID- 20140752
TI  - The "toxic dose" of system problems: why some injured workers don't return to
      work as expected.
AB  - Introduction Most workers who incur an injury on the job follow a relatively
      straightforward path through a workers' compensation claim, recovery and return
      to work. However, a minority of compensation claims is prolonged and can be
      disproportionately costly. We conducted this qualitative study in order to gain
      an understanding of systemic, process-related problems affecting injured workers
      who had failed to return to work as expected. Method A total of 69 in-depth
      interviews were conducted with injured workers with complex and extended workers'
      compensation claims and with return-to-work (RTW) providers such as health care
      providers, insurers, legal advisors, and workplaces. The study was based in
      Ontario, Canada. A modified grounded theory analysis led to the identification of
      common mechanisms in RTW problems. Results We identify problems with return to
      work and extended workers' compensation claims in dysfunctions in organizational
      dynamics across RTW systems including the workplace, healthcare, vocational
      rehabilitation and workers' compensation. These system problems are difficult to
      identify because they appear as relatively mundane and bureaucratic. These
      appeared to have damaging effects on workers in the form of a 'toxic dose'
      affecting the worker beyond the initial injury. Conclusions Worker's problems
      with extended claims were linked to RTW policies that did not easily accommodate
      conflict or power imbalances among RTW parties and by social relations and
      processes that impeded communication about RTW situations and problems. Avenues
      for intervention are located in a shift to a critical lens to RTW process that
      addresses differences of knowledge, resources, and interests among different
      parties.

PMID- 20140750
TI  - A llama-derived gelsolin single-domain antibody blocks gelsolin-G-actin
      interaction.
AB  - RNA interference has tremendously advanced our understanding of gene function but
      recent reports have exposed undesirable side-effects. Recombinant Camelid single
      domain antibodies (VHHs) provide an attractive means for studying protein
      function without affecting gene expression. We raised VHHs against gelsolin
      (GsnVHHs), a multifunctional actin-binding protein that controls cellular actin
      organization and migration. GsnVHH-induced delocalization of gelsolin to
      mitochondria or the nucleus in mammalian cells reveals distinct subpopulations
      including free gelsolin and actin-bound gelsolin complexes. GsnVHH 13
      specifically recognizes Ca(2+)-activated gelsolin (K (d) approximately 10 nM)
      while GsnVHH 11 binds gelsolin irrespective of Ca(2+) (K (d) approximately 5 nM)
      but completely blocks its interaction with G-actin. Both GsnVHHs trace gelsolin
      in membrane ruffles of EGF-stimulated MCF-7 cells and delay cell migration
      without affecting F-actin severing/capping or actin nucleation activities by
      gelsolin. We conclude that VHHs represent a potent way of blocking structural
      proteins and that actin nucleation by gelsolin is more complex than previously
      anticipated.

PMID- 20140753
TI  - Depressive symptomatology in high school students: the role of age, gender and
      academic pressure.
AB  - To clarify the prevalence of depressive symptomatology in high school students in
      Athens and to evaluate risk factors for depressive symptomatology the CES-D scale
      was administered to 713 students (age 15-18). Demographic, school performance and
      extracurricular activities data were collected. A high prevalence (26.2%) of
      depressive symptomatology (CES-D cut-off score >28) was found. Regression
      analysis showed depressive symptomatology to be associated to gender (girls had
      higher scores than boys), school record (students with a better record had lower
      scores) and the interaction of gender and grade (males were found to have higher
      depressive symptomatology scores as they grew older).

PMID- 20140754
TI  - Characteristics of patients referred to psychiatric emergency services by crisis
      intervention team police officers.
AB  - The Crisis Intervention Team (CIT) program trains police officers in crisis
      intervention skills and local psychiatric resources. Because the safety and
      appropriateness of any new intervention is a crucial consideration, it is
      necessary to ensure that CIT training does not result in excessive or
      inappropriate referrals to psychiatric emergency services (PES). Yet, aside from
      one prior report by Strauss et al. (2005) in Louisville, Kentucky, little is
      known about the comparability of patients referred to PES by CIT-trained officers
      in relation to other modes of referral. The research questions driving this
      retrospective chart review of patients referred to PES were: (1) What types of
      patients do CIT-trained officers refer to PES?, and (2) Do meaningful differences
      exist between patients referred by family members, non-CIT officers, and CIT
      trained officers? Select sociodemographic and clinical variables were abstracted
      from the medical records of 300 patients during an eight-month period and
      compared by mode of referral. Differences across the three groups were found
      regarding: race, whether or not the patient was held on the locked observation
      unit, severe agitation, recent substance abuse, global functioning, and unkempt
      or bizarre appearance. However, there were virtually no differences between
      patients referred by CIT-trained and non-CIT officers. Thus, while there were
      some expected differences between patients referred by law enforcement and those
      referred by family members, CIT-trained officers appear to refer individuals
      appropriately to PES, as evidenced by such patients differing little from those
      referred by traditional, non-CIT police officers. Trained officers do not have a
      narrower view of people in need of emergency services (i.e., bringing in more
      severely ill individuals), and they do not have a broader view (i.e., bringing in
      those not in need of emergency services). Although CIT training does not appear
      to affect the type of individuals referred to PES, future research should examine
      the effect of CIT training on the frequency of referrals or proportion of
      subjects encountered that are referred, which may be expected to differ between
      CIT-trained and non-CIT officers.

PMID- 20140756
TI  - Immunoprophylaxis of tuberculosis: an update of emerging trends.
AB  - Developing effective prophylactics to combat tuberculosis is currently in an
      exploratory stage. The HIV pandemic and emergence of multi- and extensively drug
      resistant strains of Mycobacterium tuberculosis indicate that the current
      preventive measures against this ever-evolving pathogen are inadequate. The
      currently available vaccine BCG in its present form affords variable protection
      which usually wanes with aging. Various reasons have been cited to explain the
      discrepancies in the efficacy of BCG, including generic differences in the
      different BCG vaccine strains used in immunization program throughout the world.
      The low efficacy of BCG vaccine has promoted the search for novel vaccines for
      tuberculosis. The search strategies aim at completely replacing the existing
      vaccine and/or augmenting/improving the current BCG vaccine. Among new vaccine
      candidates are live attenuated M. tuberculosis vaccines, recombinant BCG, DNA
      vaccines, subunit vaccine, and fusion protein-based vaccines. More than 200 new
      vaccine candidates have been developed as a result of research work over the past
      few years. To date, at least eight vaccine candidates are undergoing clinical
      evaluation, with a few of them successfully qualifying in the first phase of
      clinical testing. These recent advances present an optimistic insight whereby a
      new tuberculosis vaccine might be expected to be available for public use in the
      next few years.

PMID- 20140757
TI  - A case of Hughes-Stovin syndrome associated with hyperhomocysteinemia.
AB  - We report a case of Hughes-Stovin syndrome (HSS) associated with
      hyperhomocysteinemia. A 24-year-old man who has no clinical features suggestive
      of Behcet's disease was admitted for hemoptysis and dyspnea. Radiological and
      laboratory evaluation revealed multifocal pulmonary artery aneurysms involving
      bilateral segmental pulmonary artery, thrombi in right atrium and ventricle, and
      hyperhomocysteinemia. Accordingly, HSS associated with hyperhomocysteinemia was
      diagnosed, and the clinical and radiological improvement was achieved after
      treatment with prednisolone, warfarin, and folic acid.

PMID- 20140758
TI  - Methotrexate treatment in rheumatoid arthritis: management in clinical remission,
      common infection and tuberculosis. Results from a systematic literature review.
AB  - This work was performed as part of the Portuguese participation in the 3E
      Initiative 2007-2008, dedicated to the use of methotrexate (MTX) in rheumatic
      conditions. Three questions raised by Portuguese rheumatologists and considered
      relevant to clinical practice remained out of the selection of a set of ten key
      questions formulated to further establish multinational recommendations on the
      use of MTX in rheumatic diseases. The authors collected and analyzed all the
      evidence available by using a systematic literature search methodology and
      selection criteria concerning the following issues in rheumatoid arthritis (RA):
      (1) the management of MTX after clinical remission; (2) the management of MTX
      during infections and (3) the screening and treatment of tuberculosis in patients
      on MTX treatment. A total of 1,862 references were identified, of which 163 were
      selected for detailed analysis and 12 included in the final review. The evidence
      was appraised according to the Oxford Centre for Evidence-based Medicine (EBM)
      levels of evidence. Although with limited evidence, the authors concluded that:
      (1) extending the interval for MTX therapy may be a valid alternative regimen in
      a subset of RA patients in clinical remission (EBM level 2b); (2) MTX may be safe
      during some common infections in RA patients (EBM level 3b/4); (3) screening and
      treatment of TB in patients on MTX should be similar to the general population
      (EBM level 4). The evidence available to support clinical decisions in this area
      is very limited in number and quality. There is a need for further research and
      while that is unavailable, practical decisions have to rely on experience and
      expert opinion.

PMID- 20140759
TI  - Cetuximab in combination therapy: from bench to clinic.
AB  - Cetuximab, a chimeric IgG(1) monoclonal antibody directed against the ligand
      binding domain of the epidermal growth factor receptor, offers a paradigm for the
      combination of molecularly targeted therapies with cytotoxic agents. In
      preclinical models, the addition of cetuximab to chemotherapy or radiation
      therapy enhances antitumor activity. Proposed mechanisms include reducing tumor
      cell proliferation, angiogenesis, and DNA repair capacity; increasing apoptosis;
      and inducing cell cycle arrest at treatment-sensitive points. These effects may
      enhance and restore tumor sensitivity to cytotoxic therapies. In clinical trials,
      the addition of cetuximab to chemotherapy improves outcomes of patients who had
      previously failed such agents, as illustrated in irinotecan-resistant and
      oxaliplatin-refractory metastatic colorectal cancer. As initial therapy, the
      addition of cetuximab to chemotherapy extends survival in colorectal cancer, lung
      cancer, and head and neck cancer. Combining cetuximab with radiation therapy
      extends survival in locally advanced head and neck cancer. As predictive
      biomarkers are identified, it may become possible to select patients most likely
      to benefit from such combinations.

PMID- 20140760
TI  - Flavonoid transport across RBE4 cells: A blood-brain barrier model.
AB  - There is a growing interest in dietary therapeutic strategies to combat oxidative
      stress-induced damage to the Central Nervous System (CNS), which is associated
      with a number of pathophysiological processes, including Alzheimer's and
      Parkinson's diseases and cerebrovascular diseases. Identifying the mechanisms
      associated with phenolic neuroprotection has been delayed by the lack of
      information concerning the ability of these compounds to enter the CNS. The aim
      of this study was to evaluate the transmembrane transport of flavonoids across
      RBE-4 cells (an immortalized cell line of rat cerebral capillary endothelial
      cells) and the effect of ethanol on this transport. The detection and
      quantification of all of the phenolic compounds in the studied samples
      (basolateral media) was performed using a HPLC-DAD (Diode Array Detector). All of
      the tested flavonoids (catechin, quercetin and cyanidin-3-glucoside) passed
      across the RBE-4 cells in a time-dependent manner. This transport was not
      influenced by the presence of 0.1% ethanol. In conclusion, the tested flavonoids
      were capable of crossing this blood-brain barrier model.

PMID- 20140761
TI  - The physiological and morphological phenotype of a yeast mutant resistant to the
      quaternary ammonium salt N-(dodecyloxycarboxymethyl)-N,N,N-trimethyl ammonium
      chloride.
AB  - We investigated the action of the quaternary ammonium salt (QAS) called IM (N
      (dodecyloxycarboxymethyl)-N,N,N-trimethyl ammonium chloride) on Saccharomyces
      cerevisiae yeast cells. Changes in the yeast cell ultrastructure were confirmed
      by electron microscopy. We treated resistant mutant cells with QAS, and confirmed
      destruction of the mutant cytoplasm, an increase in the thickness of the cell
      wall, separation of the cell wall from the cytoplasm, and the accumulation of
      numerous lipid droplets. We also observed a relatively high production of lipids
      in the cells of the parental wild-type strain Sigma1278b and in its IM-resistant
      (IM(R)) mutant in the presence of the QAS. The IM(R) mutant showed increased
      sensitivity to CaCl(2) and SDS, and resistance to ethidium bromide,
      chloramphenicol, erythromycin and osmotic shock. It also tolerated growth at low
      pH. We suggest that the resistance to IM could be connected with the level of
      permeability of the cell membrane because the IM(R) mutant was sensitive to this
      compound in vivo in the presence of SDS and guanidine hydrochloride, which cause
      increased permeability of the cell plasma membrane.

PMID- 20140762
TI  - Acute lymphoblastic leukemia: an unusual cause of nephromegaly in infancy.

PMID- 20140763
TI  - Fulminant hepatic failure in an infant with severe dengue infection.
AB  - Fulminant hepatic failure due to dengue infection is rare, although mild liver
      dysfunction is common. Here we report a fatal case of fulminant hepatitis in an
      infant infected with dengue 3 serotype. Attention must be given to the use of
      hepatotoxic drugs in some cases of dengue especially in infants.

PMID- 20140764
TI  - Misuse of the wooden tongue depressor.

PMID- 20140765
TI  - Huge dermoid cyst of the spleen.
AB  - Primary splenic cysts are uncommon lesions of the spleen. Splenic cysts are
      classified as primary or secondary on the basis of presence or absence of an
      epithelial lining. The primary cysts are further subdivided as parasitic or non
      parasitic. The congenital non-parasitic cysts are rarely met in clinical practice
      and it constitutes approximately 10% of all splenic cysts. Congenital cysts are
      true cysts with an epithelial. Secondary cysts are in most cases posttraumatic.
      Patient at admission had lower abdominal pain and splenic cyst was asymptomatic.
      In routine abdominal pain investigation we found cyst of the spleen in diameter 2
      cm. We made serodiagnostic tests for echinococcosis which were negative. After 3
      years she came with left upper quadrant enlargement with tangible abdominal mass,
      increasing abdominal girth, decrease of appetite and sometimes vomiting. CT scan
      showed cyst enlargement in diameter 8 x 6 cm. Operative treatment was necessary
      and splenectomy was done. However, splenectomy remains a relatively safe
      procedure, associated with few complications and avoiding any future problems.

PMID- 20140766
TI  - Empyema caused by optochin sensitive Streptococcus mitis in the course of
      varicella.

PMID- 20140767
TI  - Rickets: a preventable cause of delayed walking in toddlers.

PMID- 20140768
TI  - Congenital chylothorax--successful management with chemical pleurodesis.
AB  - Congenital chylothorax is a rare entity which is characterized by abnormal
      accumulation of chyle in pleural cavity. Chylothorax presenting as non-immune
      hydrops is even rarer. We report a case of congenital bilateral chylothorax
      presenting as non immune hydrops and managed successfully with chemical
      pleurodesis. A term male baby presented at birth with bilateral pleural effusions
      and subcutaneous edema. It was initially managed with ventilation and
      intercostals drainage (ICD). After the initiation of feeds, re-accumulation of
      pleural fluid led to the diagnosis of congenital chylothorax. Management with ICD
      and octreotide was unsuccessful but responded to chemical pleurodesis with 4%
      povidine iodine done on 3 separate occasions.

PMID- 20140769
TI  - Migratory polyarthritis in familial hypercholesterolemia (type IIa
      hyperlipoproteinemia).
AB  - Metabolic disorders are often encountered in clinical practice. Some of these
      diseases are associated with dermatological and musculoskeletal manifestations.
      Familial hypercholesterolemia is a disorder of lipoprotein metabolism
      characterized by elevated cholesterol, low-density lipoprotein cholesterol,
      xanthomas and early onset atherosclerosis. Tendinitis and arthritis have been
      rarely reported in patients with familial hypercholesterolemia. Here is presented
      a case of a young girl with migratory polyarthritis, who was diagnosed as
      probable homozygote familial hypercholesterolemia with hypercholesterolemic
      arthritis. A proper knowledge of cutaneous manifestations helps to identify
      patients at risk, establish the underlying diagnosis, and start early and
      effective therapy.

PMID- 20140770
TI  - Thoraco-abdominal mature teratoma in a left diaphragmatic hernia.
AB  - This case describes a contiguous mediastinal and retroperitoneal mature teratoma
      in a congenital diaphragmatic defect, a combination that is hitherto unreported
      in literature. It substantiates embryological chronology of events during the
      cephalad migration of the primordial germ cells through the developing diaphragm,
      prior to its closure.

PMID- 20140771
TI  - Osseous involvement in pediatric Hodgkin's lymphoma.
AB  - Presented here is a report of 3 children, out of 66 total pediatric Hodgkin's
      lymphoma (HL) patients (4.5%) with bone involvement over a 3 and a half year
      period. Two patients presented with osseous lesions at the time of relapse and
      one had concurrent evidence of non-osseous disease. The clinical presentation,
      radiographic findings, histology, treatment and outcome of these patients are
      discussed. Boys and girls are nearly equally affected, local bone pain is the
      commonest symptom and B-symptoms are common. Vertebrae and pelvis are most
      frequently involved, commonly with an osteolytic picture. Nodular sclerosis is
      the predominant histological subtype. Most children received combined modality
      treatment and the overall response and survival are good.

PMID- 20140772
TI  - Morbidity among infants in South India: a longitudinal study.
AB  - To study the incidence and types of morbidity in the first year of life in a
      birth cohort, a longitudinal study. This study was undertaken in northern part of
      Karnataka state in India. Birth cohort consisted of all the children born during
      first six months of the study period. They were assessed at the time of
      enrollment and monthly follow up was done till they attained one yr of age. Out
      of the 194 newborns, 46.4% were boys and 53.6% were girls. 24.8% of newborns were
      of low birth weight and 5.1% were preterm. Four (2.1%) had congenital anomalies
      and 2.5% developed birth asphyxia. Diarrhea (10.8%) and skin diseases (8.2%) were
      the commonest morbidities in the neonatal period. The incidence of morbidity was
      3.28 per infant per yr. It was more among boys and in the second half of infancy.
      Commonest morbidities during infancy were respiratory tract infection (62.4%),
      diarrhea 42.8% and skin diseases (21.6%). Incidence of disease in infancy
      highlights the need to improve and plan health programmes.

PMID- 20140773
TI  - Matrix metalloproteinase-9 and its inhibitor in idiopathic pulmonary
      hemosiderosis.

PMID- 20140774
TI  - Post obstructive pulmonary edema following accidental strangulation.

PMID- 20140775
TI  - Influence of parental obesity on school children.
AB  - OBJECTIVE: To find out the association between parental obesity and childhood
      obesity. METHODS: Children in middle schools were screened for obesity. For each
      obese child two controls were studied. RESULTS: Parental history of obesity was
      present for 32.7% of obese children. Children with parental history of obesity
      showed 25.2 times more chances of developing obesity than controls. 33.8% of the
      obese girls and 31.6% of the obese boys had history of parental obesity. If the
      father was obese, boys had 6.5 times more chance and girls had 40.1 times more
      chance of developing obesity. Mother's obesity had an influence on 23.7 % of the
      boys and only 16 % of the girls. CONCLUSION: The childhood obesity has been
      influenced by genetic factors in the present study and it also shows that
      maternal obesity mainly passes to boys and paternal obesity to girls.

PMID- 20140776
TI  - BMI and serum lipid.

PMID- 20140777
TI  - Head injuries in children resulting from the fall of television.
AB  - Case records of children admitted with head injury due to TV fall in a pediatric
      tertiary care hospital in Chennai, during March 2007-February 2008 were analysed
      retrospectively. Out of the 11 children admitted 6 (54%) were in 1-2 yr age
      group. Bleeding from the ear, nose and throat was the commonest, finding followed
      by a skull fracture, seen on imaging studies. These were observed in 9 (81.81%)
      and 8 (72.8%) children respectively. There was no mortality.

PMID- 20140778
TI  - Prepubertal gynecomastia a rare complication of growth hormone therapy.
AB  - We report a case of prepubertal gynecomastia diagnosed during growth hormone (GH)
      treatment. In our patient gynecomastia appeared 6 months after GH was started.
      This condition appears to be self-limited and benign. In our patient
      gynaecomastia resolved on its own.

PMID- 20140779
TI  - Status epilepticus and capillary leak syndrome in a neonate related to perinatal
      hypoxic-ischemic encephalopathy.
AB  - Hypoxic-ischemic cerebral injury that occurs during the perinatal period is one
      of the most commonly recognized cause of long-term neurological deficit in
      children, often referred to as cerebral palsy. We describe a case with capillary
      leak syndrome and seizures to co-morbid status epilepticus related to perinatal
      hypoxic-ischemic encephalopathy in newborn period.

PMID- 20140780
TI  - Gossypiboma in a child presenting as peri-nephric abscess.

PMID- 20140781
TI  - Myasthenia gravis developing in a patient with CNS lymphoma.
AB  - A patient was initially diagnosed with right basal ganglia lymphoma causing left
      hemiparesis. His disease was resistant to intravenous methotrexate, so he
      received radiation therapy with remarkable regression of the mass. However, 6
      months after his initial diagnosis, he developed symmetric weakness of the
      proximal muscles. Electromyography was consistent with myasthenia gravis and anti
      acetylcholine receptor antibodies were elevated. Treatment with pyridostigmine
      and corticosteroids improved his symptoms. The residual lymphoma was further
      treated with rituximab and temozolomide with complete resolution. Pyridostigmine
      and corticosteroids were stopped after 14 months of initiation with good results.
      Our case is the first case report of paraneoplastic myasthenia gravis developing
      in a patient with primary CNS lymphoma. The diagnosis of paraneoplastic
      myasthenia should be considered in patients with CNS lymphoma who develop muscle
      weakness and speech problems.

PMID- 20140782
TI  - Paroxysmal nocturnal hemoglobinuria turning Coombs-positive.

PMID- 20140783
TI  - [Is the determination of biomarkers worth its price? Review of the literature
      taking brain natriuretic peptides (BNP) as an example].
AB  - Heart failure is an important cardiac disease with an increasing prevalence in
      Western societies. In addition to a significant reduction of the patient's
      physical capability and quality of life, cardiac insufficiency is associated with
      considerable expenditure by national health care systems. A number of imaging
      techniques are available for the detection of heart failure (e.g.,
      echocardiography), and the use of biomarkers such as brain natriuretic peptides
      (BNP or NT-proBNP) becomes increasingly popular in the process of screening and
      diagnosis. Until now, there is a lack of information regarding health-economic
      aspects of this biomarker use. For this reason, a systematic literature search
      was conducted in MEDLINE including all relevant studies published up to and
      including August 2009. The primary objective was to summarize the main findings
      of all relevant investigations which focus on health-economic aspects of BNP use
      as well as NT-proBNP use. Out of 64 initial search results, 13 relevant studies
      were identified which met the inclusion criteria. Eleven studies were finally
      included in this literature review. Although the methodology of these studies was
      very heterogeneous, the majority of investigations indicate that the use of BNP
      and NT-proBNP, respectively, is a cost-effective procedure for heart failure
      diagnosis and prognosis, as well as for heart failure screening. However, keeping
      in mind that the transferability of economics study results is limited due to a
      number of differences between national health care systems, there are no
      investigations with a focus on the financial implications for Germany. Further
      research is required in this context.

PMID- 20140784
TI  - [Biomarker for diagnosis of rejection after heart transplantation].
AB  - Heart transplantation is an established therapeutic modality in patients with end
      stage heart failure. In the 1st year after transplantation acute cellular
      rejection is still important. The diagnosis of acute cellular rejection is based
      on the histological evaluation of endomyocardial biopsy (EMB) specimens. EMB is
      an invasive procedure with a definite risk and poor tolerance in some patients.
      Imaging methods like echocardiography and magnetic resonance imaging as well as
      intracardiac ECG have been used for noninvasive diagnosis of acute cellular
      rejection. In addition, a large number of circulating biomarkers have been
      evaluated for noninvasive diagnosis of rejection. B-type natriuretic peptide,
      troponin and inflammatory markers are the most important biomarkers in this
      field. Although these parameters are useful, none of them has the potential to
      replace EMB as the gold standard for diagnosis of rejection. In the near future
      microarray technology might get important for diagnosis of acute cellular
      rejection. Using microarray technique gene expression profiles can be detected,
      which are associated with an increased risk for rejection. Ongoing studies will
      demonstrate, whether microarrays can at least reduce the number of EMBs.

PMID- 20140786
TI  - Call for standards in technical documentation of intracoronary stents.
AB  - At present, the product information of intracoronary stents provided by the
      industry contains only limited technical data restricting judgments on the in
      vivo performance of individual products. Available experimental and clinical
      evidence suggests that interventional target sites display highly heterogeneous
      biomechanical behavior needed to be matched by specific stent and stent delivery
      system characteristics. To allow individualized stent-lesion matching, both,
      understanding of biomechanical properties of the atherosclerotic coronary artery
      lesions and expert knowledge of the intracoronary stent systems, are required.
      Here, the authors review some of the initial data on mechanical properties of
      coronary artery lesions potentially relevant to stenting and suggest standards
      for technical documentation of intracoronary stents.

PMID- 20140785
TI  - Congenital heart disease in pregnancies complicated by maternal diabetes
      mellitus. An international clinical collaboration, literature review, and meta
      analysis.
AB  - PURPOSE: Investigation of the incidence and distribution of congenital structural
      cardiac malformations among the offspring of mothers with diabetes type 1 and of
      the influence of periconceptional glycemic control. METHODS: Multicenter
      retrospective clinical study, literature review, and meta-analysis. The incidence
      and pattern of congenital heart disease in the own study population and in the
      literature on the offspring of type 1 diabetic mothers were compared with the
      incidence and spectrum of the various cardiovascular defects in the offspring of
      nondiabetic mothers as registered by EUROCAT Northern Netherlands. Medical
      records were, in addition, reviewed for HbA(1c) during the 1st trimester.
      RESULTS: The distribution of congenital heart anomalies in the own diabetic study
      population was in accordance with the distribution encountered in the literature.
      This distribution differed considerably from that in the nondiabetic population.
      Approximately half the cardiovascular defects were conotruncal anomalies. The
      authors' study demonstrated a remarkable increase in the likelihood of visceral
      heterotaxia and variants of single ventricle among these patients. As expected,
      elevated HbA(1c) values during the 1st trimester were associated with offspring
      fetal cardiovascular defects. CONCLUSION: This study shows an increased
      likelihood of specific heart anomalies, namely transposition of the great
      arteries, persistent truncus arteriosus, visceral heterotaxia and single
      ventricle, among offspring of diabetic mothers. This suggests a profound
      teratogenic effect at a very early stage in cardiogenesis. The study emphasizes
      the frequency with which the offspring of diabetes-complicated pregnancies suffer
      from complex forms of congenital heart disease. Pregnancies with poor 1st
      trimester glycemic control are more prone to the presence of fetal heart disease.

PMID- 20140788
TI  - Image of the month. Bluish-black pigmentation of the sclera and the aortic valve
      in a patient with alkaptonuric ochronosis.

PMID- 20140787
TI  - [Electromyostimulation (EMS) in cardiac patients. Will EMS training be helpful in
      secondary prevention?].
AB  - BACKGROUND: Current guidelines concerning the treatment of patients with chronic
      congestive heart failure (CHF) include ergospirometry-directed dynamic exercises
      on a daily basis. Several prospective, randomized trials have confirmed its
      positive influence on clinical symptoms and prognosis of the disease. Patients
      with stable coronary artery disease (CAD) can benefit from a 27% reduction of
      mortality, as shown in meta-analyses of several studies. By contrast, patients
      with CHF have traditionally been discouraged from physical activities, which may
      have had detrimental consequences. They became even less able to participate in
      daily activities that in turn hastened the disease-driven atrophies of skeletal
      muscles. On the other hand, well-adjusted endurance training at 50-70% of maximum
      oxygen uptake was shown to improve overall fitness. In a recent metaanalysis, the
      mortality of patients with CHF was reduced by 35% by sports, and the rate of
      hospitalizations dropped by 28%. It is a well-perceived clinical problem that
      successful treatment is not possible without intensive guidance and a close
      therapeutic relationship. Being left in their routine situation and
      circumstances, the majority of patients cannot cope with the day-to-day challenge
      of an independent, active lifestyle. Among the primary reasons not to sustain
      physical activity are mental, psychological or social barriers. PATIENTS AND
      METHODS: The authors have begun, in a cohort of patients with CHF, a prospective
      pilot study to investigate the impact of, and attitude to, electromyostimulation
      (EMS). Unique features of this treatment include its passive nature that remains
      independent of mental attitude. RESULTS: An up to 96% increase of peak oxygen
      uptake at the anaerobic threshold could be shown (pre- vs. posttraining phase,
      VO(2at) 19.39 [+/- 5.3] ml/kg vs. 24.25 [+/- 6.34] ml/kg). The diastolic blood
      pressure decreased significantly. A 14% gain in muscle volume was observed, while
      overall body weight remained unchanged. All patients kept up the training until
      the conclusion of the study and found their overall fitness to be considerably
      improved. CONCLUSION: The results may indicate the enormous potential of EMS for
      the treatment of patients within the cardiologic arena, especially those with
      CHF.

PMID- 20140789
TI  - Primary PCI for acute myocardial infarction in a patient with idiopathic
      thrombocytopenic purpura. A case report and review of the literature.
AB  - BACKGROUND AND PURPOSE: The occurrence of acute myocardial infarction (AMI) in
      patients with idiopathic thrombocytopenic purpura (ITP) is rare, especially when
      the platelet count is low. Since only few case reports have been published, there
      are no recommendations for the management of thrombocytopenic patients with AMI.
      The aim of the present study is to discuss different aspects of this challenging
      issue and to review limited data available in the literature. CASE STUDY: An 80
      year-old patient with ITP (platelet count 5 . 10(9)/l) is presented who developed
      an AMI (ST segment elevation myocardial infarction) and was successfully treated
      by primary percutaneous coronary intervention (PCI). CONCLUSION: Considering the
      high bleeding risk in patients with ITP and AMI, careful balance between usual
      anticoagulation and antiplatelet therapy on the one hand, and efforts to raise
      platelet count on the other hand are needed.

PMID- 20140791
TI  - Desire for a child among HIV-infected women receiving antiretroviral therapy in
      Cameroon: results from the national survey EVAL (ANRS 12-116).
AB  - The majority of HIV-infected people in sub-Saharan Africa are women, many of
      reproductive age. Cameroon is severely hit by the AIDS epidemic and has developed
      a large national program for improving access to antiretroviral treatment (ART).
      The reproductive intentions of women living with HIV/AIDS (WLHA) who obtain
      access to ART in this country remain poorly documented. Our study aimed at
      exploring factors associated with the desire to have a child among 1433 ART
      treated fertile WLHA aged <50. Analyses were based on data collected during the
      national cross-sectional survey EVAL (ANRS 12-116), which was conducted between
      September 2006 and March 2007 in 27 HIV care centers in Cameroon. Logistic
      regression was used to explore factors associated with women's desire to have a
      child, defined as reporting the wish to have a/another child. A total of 791
      women (55%) reported the desire to have a child. After adjusting for age,
      matrimonial status, number of biological children, and sexual activity, the main
      factors independently associated with this desire in a multivariate analysis were
      having a good physical health-related quality of life (1.02 [1.01-1.03] for a one
      point increment on the 12-item Short-Form Health Survey scale) and a CD4 count at
      ART initiation <200 cells/mm(3) (1.7 [1.2-2.4]). As a conclusion, the desire to
      have a child is frequent among ART-treated WLHA in Cameroon. HIV care and family
      planning programs should be integrated more thoroughly in order to support WLHA's
      reproductive choices.

PMID- 20140792
TI  - Validation of the MOS-HIV as a measure of health-related quality of life in
      persons living with HIV and liver disease.
AB  - BACKGROUND: Management of human immunodeficiency virus (HIV) infection with
      potent antiretroviral medication has transformed HIV into a chronic condition and
      has shifted much of the burden of disease to co-morbid conditions such as liver
      disease (LD). LD alone has been shown to have a significant effect on one's
      health-related quality of life (HRQOL). Clinical evidence suggests that the
      growing number of persons living with HIV+LD may have a poorer HRQOL than persons
      with HIV without LD. To date, the widely accepted instrument to assess HRQOL,
      Medical Outcomes Study-HIV Health Survey (MOS-HIV), has not been evaluated for
      reliability and validity in a population of HIV-infected persons with LD.
      METHODS: HRQOL was prospectively assessed using the MOS-HIV in a sample of 532
      HIV-infected adults on antiretroviral therapy (n=305 HIV and n=227 HIV+LD). In
      addition, participants completed standardized questionnaires of sociodemographics
      and co-morbid conditions. RESULTS: The psychometric properties of the MOS-HIV
      were supported by testing reliability and construct, convergent, discriminative,
      and predictive validity. The MOS-HIV discriminated between those persons living
      with HIV with and without LD on the basis of the physical function subscale
      scores (p=0.018). CONCLUSION: This study found the MOS-HIV valid and reliable
      instrument in persons with HIV+LD.

PMID- 20140793
TI  - The benefits of using a mixed methods approach--quantitative with qualitative--to
      identify client satisfaction and unmet needs in an HIV healthcare centre.
AB  - Research into patient satisfaction with HIV ambulatory healthcare facilities is
      limited due to confidentiality restraints, the short history of the condition and
      the stigma attached. Furthermore, most satisfaction studies of this client group
      have not used mixed methods (quantitative with qualitative) despite its
      increasing use since the 1990s in healthcare research. This cross-sectional study
      demonstrates how a mixed methods approach is beneficial in assessing HIV client
      satisfaction and in identifying unmet needs in HIV healthcare. Conducted at the
      largest ambulatory HIV healthcare centre in Australia, this study consisted of
      two phases conducted sequentially: Phase One, a quantitative self-administered
      questionnaire survey, provided an overall statistical picture of satisfaction
      levels. This was followed by Phase Two, qualitative semi-structured face-to-face
      interviews, which enabled in-depth investigation of the reasons for
      satisfaction/dissatisfaction. Phase One had 166 respondents, giving a high
      response rate of 71%, while Phase Two had 22 participants. The study demonstrates
      the three advantages of using a mixed methods approach. Firstly, it increased the
      comprehensiveness of overall findings, by showing how qualitative data (Phase
      Two) provided explanations for statistical data (Phase One). Secondly, it
      expanded the dimensions of the research topic, as Phase Two enabled investigation
      of the determinants of satisfaction/dissatisfaction more broadly after assessing
      the client satisfaction levels in Phase One. Thirdly, it increased the
      methodological rigour as findings in both phases could be checked for
      consistency. Thus using a mixed methods approach can greatly enhance our
      understanding of client satisfaction in HIV/AIDS research.

PMID- 20140794
TI  - A qualitative study of participant adherence in a randomized controlled trial of
      herpes suppressive therapy for HIV prevention in Tanzania.
AB  - Poor participant adherence to treatment may contribute to lack of impact in some
      biomedical HIV prevention trials. This qualitative study explored adherence in a
      randomized controlled trial of herpes suppressive therapy to reduce HIV
      acquisition and infectivity among 1305 Tanzanian women. The trial found
      participants completed 72% of visits on treatment; 52-56% of women on treatment
      had > or = 90% adherence by pill count estimate; and between six and nine months
      30/86 (35%) of urine samples from acyclovir recipients tested acyclovir negative,
      and 7/86 (8%) from placebo recipients tested acyclovir positive. Twenty in-depth
      interviews (IDIs) were conducted after 30 months with respondents randomly
      selected from "acyclovir negative" acyclovir recipients and "acyclovir positive"
      placebo recipients, or by preliminary pill count adherence categories ("under
      users," "good users," and "over users"). Almost all respondents reported
      appropriate adherence and positive trial attitudes, e.g., trusting staff,
      appreciating services, perceiving pills as beneficial. Fourteen understood
      placebo use, and six understood the trial purpose. Notably, 5/9 acyclovir
      recipients and 1/11 placebo recipients believed their pills had treated pre
      existing sexually transmitted infections. Limited understanding did not
      negatively affect reported adherence. Reported adherence problems usually related
      to illness, travel, and/or family obligations (e.g., husband's disapproval).
      "Acyclovir positive" placebo recipients denied taking other participants' pills.
      The IDIs also did not resolve discrepant reports of pill loss or theft.
      Biomedical HIV interventions often have strong behavioral components that require
      close attention during intervention development, trial design, and process and
      impact evaluation. This study identified topics which warrant further
      consideration, including: information reinforcement and comprehension assessment
      throughout a trial for long-term participant understanding; involving partners in
      adherence promotion activities; strategizing with participants to maintain
      adherence during familial illnesses or other crises; and close monitoring,
      identification, and follow-up of (1) individuals with discrepant biological
      tests, and (2) other sources of the treatment in the trial area. Methodological
      research is also needed to improve adherence measures.

PMID- 20140795
TI  - Explaining perceived ability among older people to provide care as a result of
      HIV and AIDS in South Africa.
AB  - In South Africa, older people have become the primary caregivers of children and
      grandchildren infected or affected by HIV and AIDS. This study explores the
      determinants of the perceived ability to care for children and grandchildren in
      the domains of providing nursing care, communicating with (grand) children,
      generating income and to relax. Structured one-on-one interviews were conducted
      among 409 isiXhosa speaking older people in two sites in the Eastern Cape
      Province of South Africa. Results showed that perceived ability among older
      people to provide nursing care was primarily dependent on the level of knowledge
      on accessing grants and personal norm towards providing care. Perceived ability
      to communicate effectively with children and grandchildren was most strongly
      predicted by a positive attitude towards communication and perceived ability to
      provide income was influenced by a more negative attitude towards people living
      with HIV or AIDS. Perceived ability to relax was dependent on more negative
      attitudes towards communication, lower perceived responsibility to provide income
      and a higher perceived behaviour control over providing nursing care. The
      findings of this study add relevant information to understanding the psychosocial
      context in which older people provide HIV and AIDS related care and support the
      development of targeted programmes to assist older people in their role as
      caregiver.

PMID- 20140796
TI  - Evaluation of DNA extraction methods from complex phototrophic biofilms.
AB  - Phototrophic biofilms are used in a variety of biotechnological and industrial
      processes. Understanding their structure, ie microbial composition, is a
      necessary step for understanding their function and, ultimately, for the success
      of their application. DNA analysis methods can be used to obtain information on
      the taxonomic composition and relative abundance of the biofilm members. The
      potential bias introduced by DNA extraction methods in the study of the diversity
      of a complex phototrophic sulfide-oxidizing biofilm was examined. The efficiency
      of eight different DNA extraction methods combining physical, mechanical and
      chemical procedures was assessed. Methods were compared in terms of extraction
      efficiency, measured by DNA quantification, and detectable diversity (16S rRNA
      genes recovered), evaluated by denaturing gradient gel electrophoresis (DGGE).
      Significant differences were found in DNA yields ranging from 116 +/- 12 to 1893
      +/- 96 ng of DNA. The different DGGE fingerprints ranged from 7 to 12 bands.
      Methods including phenol-chloroform extraction after enzymatic lysis resulted in
      the greatest DNA yields and detectable diversity. Additionally, two methods
      showing similar yields and retrieved diversity were compared by cloning and
      sequencing. Clones belonging to members of the Alpha-, Beta- and Gamma-
      proteobacteria, Bacteroidetes, Cyanobacteria and to the Firmicutes were recovered
      from both libraries. However, when bead-beating was applied, clones belonging to
      the Deltaproteobacteria were also recovered, as well as plastid signatures.
      Phenol-chloroform extraction after bead-beating and enzymatic lysis was therefore
      considered to be the most suitable method for DNA extraction from such highly
      diverse phototrophic biofilms.

PMID- 20140798
TI  - Outflow boundary conditions for 3D simulations of non-periodic blood flow and
      pressure fields in deformable arteries.
AB  - The simulation of blood flow and pressure in arteries requires outflow boundary
      conditions that incorporate models of downstream domains. We previously described
      a coupled multidomain method to couple analytical models of the downstream
      domains with 3D numerical models of the upstream vasculature. This prior work
      either included pure resistance boundary conditions or impedance boundary
      conditions based on assumed periodicity of the solution. However, flow and
      pressure in arteries are not necessarily periodic in time due to heart rate
      variability, respiration, complex transitional flow or acute physiological
      changes. We present herein an approach for prescribing lumped parameter outflow
      boundary conditions that accommodate transient phenomena. We have applied this
      method to compute haemodynamic quantities in different physiologically relevant
      cardiovascular models, including patient-specific examples, to study non-periodic
      flow phenomena often observed in normal subjects and in patients with acquired or
      congenital cardiovascular disease. The relevance of using boundary conditions
      that accommodate transient phenomena compared with boundary conditions that
      assume periodicity of the solution is discussed.

PMID- 20140797
TI  - The effects of copper additives on the quantity and cell viability of adherent
      Staphylococcus epidermidis in silicone implants.
AB  - This in vitro study evaluated the antibacterial effect of copper additives in
      silicone implants. Specimens of a standard silicone material used in breast
      augmentation and modified copper-loaded silicone specimens were prepared and
      incubated in a Staphylococcus epidermidis suspension (2 h, 37 degrees C). After
      the quantification of adhering staphylococci using a biofluorescence assay
      (Resazurin), the viability of the adhering bacterial cells was quantified by live
      or dead cell labeling in combination with fluorescence microscopy. In the
      Resazurin fluorometric quantification, a higher amount of adhering S. epidermidis
      cells was detected on pure silicone (4612 [2319/7540] relative fluorescence units
      [rfu]) than on silicone with copper additives (2701 [2158/4153] rfu).
      Additionally, a significantly higher amount of adhering bacterial cells (5.07%
      [2.03%/8.93%]) was found for pure silicone than for silicone with copper
      additives (1.72% [1.26%/2.32%]); (p < 0.001). Calculations from live or dead
      staining showed that the percentage of dead S. epidermidis cells adhered on pure
      silicone (52.1%) was significantly lower than on silicone with copper additives
      (79.7%); (p < 0.001). In vitro, silicone material with copper additives showed
      antibacterial effects against S. epidermidis. Copper-loaded silicone may prevent
      bacterial colonization, resulting in lower infection rates of silicone implants.

PMID- 20140799
TI  - St. John's wort may improve some symptoms of attention-deficit hyperactivity
      disorder.
AB  - There is evidence for the efficacy of noradrenaline and serotonin reuptake
      inhibitors treating attention-deficit hyperactivity disorder (ADHD). In this open
      trial, we checked St. John's wort, a serotonin and noradrealine reuptake
      inhibitor, and actually used as an antidepressant, for this indication. Three 14
      16-year-old male psychiatric outpatients, diagnosed with ADHD have been rated at
      baseline and while taking St. John's wort or a placebo, respectively, by the
      Conner Scale and by the Continuous Performance Test, to determine its efficacy as
      a treatment option for ADHD. Patients' mean scores improved for Conners'
      hyperactivity, inattention and immaturity factors. Although the sample size is
      very small and therefore generalisation is very difficult, this observation
      indicates that St. John's wort might be a slightly effective treatment for ADHD
      also.

PMID- 20140800
TI  - Antioxidant properties and principal phenolic phytochemicals of Indian medicinal
      plants from Asclepiadoideae and Periplocoideae.
AB  - The subfamily Asclepiadoideae (Apocynaceae) and the closely-related
      Periplocoideae are sources of many indigenous Indian medicinal plants. We
      surveyed antioxidant properties and total phenolic and flavonoid contents of 15
      samples, representing 12 Indian medicinal plant species from these subfamilies.
      Total antioxidant assay was performed using the 2,2-azinobis-3
      ethylbenzothiazoline-6-sulfonic acid and ferric-reducing antioxidant power
      methods. Total phenolic and flavonoid contents were measured using colourimetric
      methods. Principal phenolic compounds were detected by liquid chromatography-mass
      spectrometry (LC-MS). The highest antioxidant capacity and high levels of total
      phenolics and flavonoids were found in the leaves of Decalepis hamiltonii. The
      stems of Sarcostemma brevistigma exhibited the highest xanthine oxidase (XO)
      inhibitory activity. The roots of Hemidesmus indicus showed the highest OH(-)
      radical scavenging activity. In general, Periplocoideae members exhibited higher
      antioxidant activity than Asclepiadoideae members. The highly significant and
      positive correlations (R > 0.914) between total antioxidant capacity parameters
      and total phenolic content indicated that the phenolic compounds contributed
      significantly to the antioxidant activity of the tested plant samples. The
      principal phenolic phytochemicals from these plants were identified by LC-MS,
      including flavonoids, phenolic acids and phenolic terpenoids. Chlorogenic acid
      and rutin were detected in almost all of the plant samples. The LC-MS analysis
      provided full fingerprints of the principal phenolic compounds in the medicinal
      plants from these two subfamilies, which are useful for their authentication and
      quality evaluation.

PMID- 20140801
TI  - Isolation of acetylcholinesterase inhibitory alkaloids from Nerine bowdenii.
AB  - Alzheimer's disease (AD) is associated with a steady loss of attention and
      memory, which has been correlated with the impairment of brain cholinergic
      neurotransmission, particularly a deficit of cholinergic neurons in the nucleus
      basalis of Meynert. Therefore, one of the methods that has proven successful in
      the treatment of AD is the use of inhibitors of acetylcholinesterase (AchE) to
      supplement the acetylcholine level. Herein we describe the isolation of several
      AchE-inhibiting alkaloids from the bulbs of Nerine bowdenii, an Amaryllidaceae
      species. For the first time 11-O-acetylambelline and filofiline, previously
      reported from Brunsvigia josephinea and Nerine filifolia, respectively, were
      isolated.

PMID- 20140802
TI  - Molecular evaluation of extracellular activity of medicinal herb Clinacanthus
      nutans against herpes simplex virus type-2.
AB  - Clinacanthus nutans (Burm. f.) Lindau (C. nutans), a medicinal herb belonging to
      the family Acanthaceae, has traditionally been used in herpes simplex virus (HSV)
      treatment in Thailand. Clinical trials have indicated that topical preparations
      produced from its extracts were effective in HSV-2 treatment. However, there is
      no clear evidence of the mechanism of action or a molecular target of C. nutans.
      In this study, the extracellular activity of C. nutans extracts against HSV-2
      infected on HEp-2 cells was investigated in terms of its molecular aspects. HSV-2
      was treated with the extracts and adsorped into the HEp-2 cells. After infection,
      HSV-2 DNA quantities in the infected cells were assessed and compared by the
      quantitative dot blot hybridisation technique. The results showed that treating
      the viruses with either less or more highly purified extracts before infection
      resulted in great reductions of viral infectivity. Further investigation was
      performed by Western blot analysis to determine the activities of the extracts on
      the viral proteins. At least eight viral proteins of the infected cell proteins
      (ICP) and some structural proteins, including 146, 125, 78, 69, 55, 44, 40 and 20
      KDa proteins, were depleted and reduced gradually with higher and lower
      concentrated herb extracts, respectively. These suggest that the C. nutans
      extracts highly inactivated or inhibited HSV-2 before infection.

PMID- 20140803
TI  - A crystal lapiferin derived from Ferula vesceritensis induces apoptosis pathway
      in MCF-7 breast cancer cells.
AB  - Ferula vesceritensis is a plant that is used in the traditional medicine in
      Algeria. Chromatographic investigation of the methylene chloride/methanol extract
      of the aerial parts of F. vesceritensis afforded a crystal carotene sesquiterpene
      designed lapiferin (10alpha-acetoxy-6alpha-angeloyloxy-8alpha,9alpha-epoxy-trans
      caxotan-4beta-ol) for the first time from this species. The structure was
      determined by comprehensive NMR studies, including DEPT, COSY, NOE, HMQC, HMBC
      and HRMS, and X-ray data of lapiferin. We report here for the first time the
      isolation of lapiferin from F. vesceritensis as a new natural source, and we
      additionally report the first X-ray data for lapiferin. We also report for the
      first time the specific anti-cancer activity of lapiferin against human breast
      cancer cells (MCF-7), which is due to apoptosis and not necrosis. Moreover, we
      have identified for the first time the cell death pathway induced by lapiferin in
      human breast cancer cells, and also that lapiferin evokes multiple consequences
      that trigger apoptotic cell death, involving the enhancement of DNA
      fragmentation, the activation of caspases and the induction of histone
      acetylation in MCF-7 cells. In conclusion, we record here F. vesceritensis as a
      new natural source of lapiferin and its first X-ray analysis, and the promising
      specific anti-cancer activity against human breast cancer of lapiferin and
      accordingly F. vesceritensis extract.

PMID- 20140804
TI  - Antihyperglycaemic effect of an unusual amino acid (4-hydroxyisoleucine) in
      C57BL/KsJ-db/db mice.
AB  - The present report confirms the anti-hyperglycaemic and anti-dyslipidemic
      properties of 4-hydroxyisoleucine, an unusual amino acid isolated from Trigonella
      foenum-graecum seeds, for the first time in a well-characterised model of type II
      diabetes, i.e. db/db mice. 4-Hydroxyisoleucine, when given orally to these mice
      at 50 mg kg(-1) dose level, significantly (p < 0.05) declined their elevated
      blood glucose, plasma insulin, triglycerides, total cholesterol, low-density
      lipoprotein-cholesterol levels and raised their declined plasma high-density
      lipoprotein-cholesterol level. These results indicate that 4-hydroxyisoleucine
      exhibits significant potential as an anti-diabetic agent by suppressing
      progression of type II diabetic states that is suggested by enhancement of
      insulin sensitivity and glucose uptake in peripheral tissue.

PMID- 20140805
TI  - A new anti-inflammatory flavonol glycoside from Alchornea floribunda leaves.
AB  - Alchornea floribunda leaves are widely used in African ethnomedicine for the
      management of acute and chronic inflammatory disorders. In the present study,
      bioactivity-guided fractionation of the ethyl acetate fraction of the methanol
      leaf extract of the plant material led to the isolation of a new flavonol
      glycoside (AFF1). The anti-inflammatory activity of this novel compound was
      evaluated using egg albumen-induced rat paw oedema as a model of inflammation.
      AFF1 showed significant inhibition of the rat paw oedema in a dose-dependent
      manner. The activity of AFF1 (50 mg kg(-1)) was higher than that of the standard
      anti-inflammatory drug, aspirin (100 mg kg(-1)). The compound also significantly
      (p < 0.001) inhibited heat-induced haemolysis of human erythrocytes in vitro. The
      structure of AFF1 was elucidated as 3,5,7,3'-tetrahydroxyflavone-3-O-alpha-L
      rhamnoside, using a combination of UV, IR, 1D and 2D (COSY) 1H-NMR spectroscopy.
      This compound, in part, accounts for the anti-inflammatory effect of A.
      floribunda leaves.

PMID- 20140806
TI  - Dual effects of ouabain, digoxin and proscillaridin A on the regulation of
      apoptosis in human fibroblasts.
AB  - In this study, we looked at the effect of ouabain, digoxin and proscillaridin A
      on human fibroblasts. These data show that low concentrations of ouabain, digoxin
      and proscillaridin A can activate proliferation of human fibroblasts, suggesting
      that the Na+, K+-adenosine triphosphatase complex may act as a transducing
      receptor. It was shown that 30 nM ouabain, digoxin and proscillaridin A
      stimulated an antiapoptotic action by the increase in the level of phosphorylated
      extracellular signal-regulated kinases (P-ERK 1/2). Ouabain, digoxin and
      proscillaridin A only at the relatively high concentration of 300 nM increased
      intracellular Ca2+ concentration, activated caspase-3 and induced apoptosis in
      human fibroblasts. In terms of reduction in cell viability, antiproliferative and
      apoptotic activity, these cardiac glycosides rank in the order proscillaridin A
      >digoxin >ouabain.

PMID- 20140807
TI  - Chitosan enhances xanthone production in Hypericum perforatum subsp.
      angustifolium cell cultures.
AB  - Hypericum perforatum is an important medicinal plant containing numerous
      biologically active compounds. The effect of chitosan elicitation on xanthone
      biosynthesis in calli and in cell suspension cultures of H. perforatum subsp.
      angustifolium was evaluated. Elicited cell cultures showed an increase in
      xanthone production and a simultaneous decrease in flavonoid production. Chitosan
      also induced the production of 1,7-dihydroxyxanthone (euxanthone) and cadensin G,
      which were not detected in either the calli nor the non-elicited cell cultures.
      1,7-Dihydroxyxanthone was in part (21%) released in the culture medium.

PMID- 20140808
TI  - Isolation of a new glycoside from starfish, Asterias amurensis Lutken, and its
      stimulation activity on the proliferation of the UMR106 cell.
AB  - A new glycoside compound (1) was isolated from the starfish Asteria amurensis
      Lutken. The structure for compound 1 was identified as 1-O-{beta-D
      quinovopyranosyl-(1-2)-beta-D-fucopyranosyl-(1-4)-[beta-D-fucopyranosyl(1-2)]
      beta-D-quinovopyranosyl}-butanol by extensive NMR experiments as well as chemical
      evidence. The effects of compound 1 on UMR106 cell proliferation were screened by
      MTT assay. The results indicate that compound 1 (0.01-100 microM) significantly
      promotes osteoblastic proliferation.

PMID- 20140809
TI  - Phytochemical investigation and evaluation of in vitro free radical scavenging
      activity of Tabernaemontana divaricata Linn.
AB  - We evaluate the in vitro free radical scavenging activity of the leaves of
      Tabernaemontana divaricata Linn. Petroleum ether, ethanol and aqueous extracts of
      T. divaricata were prepared with successive extraction in a soxhlet apparatus.
      Each extract was selected to study the free radical scavenging activity by
      superoxide scavenging assay method. It was found that the aqueous extract
      contained carbohydrates, glycosides, amino acids, flavonoids, tannins, alkaloids,
      and steroids, and the ethanolic extract contained glycosides, amino acids,
      flavonoids, tannins, alkaloids and steroids. The ethanolic extract of T.
      divaricata showed 58.7 +/- 0.62% inhibition in the superoxide scavenging model.
      The aqueous extract also showed almost similar activity (54.9 +/- 0.53% compared
      to the ethanolic extract), while petroleum ether extract showed poor inhibition
      of superoxide scavenging activity. All extracts showed the dose- and time
      dependent inhibition of the superoxide scavenging activity.

PMID- 20140810
TI  - Diagnosing and alleviating the impact of performance pressure on mathematical
      problem solving.
AB  - High-pressure academic testing situations can lead people to perform below their
      actual ability levels by co-opting working memory (WM) resources needed for the
      task at hand (Beilock, 2008). In the current work we examine how performance
      pressure impacts WM and design an intervention to alleviate pressure's negative
      impact. Specifically, we explore the hypothesis that high-pressure situations
      trigger distracting thoughts and worries that rely heavily on verbal WM.
      Individuals performed verbally based and spatially based mathematics problems in
      a low-pressure or high-pressure testing situation. Results demonstrated that
      performance on problems that rely heavily on verbal WM resources was less
      accurate under high-pressure than under low-pressure tests. Performance on
      spatially based problems that do not rely heavily on verbal WM was not affected
      by pressure. Moreover, the more people reported worrying during test performance,
      the worse they performed on the verbally based (but not spatially based) maths
      problems. Asking some individuals to focus on the problem steps by talking aloud
      helped to keep pressure-induced worries at bay and eliminated pressure's negative
      impact on performance.

PMID- 20140811
TI  - A year of successful cancer vaccines points to a path forward.
AB  - Results from recent clinical trials of the therapeutic vaccines sipuleucel-T
      (Dendreon Corp), PROSTVAC-VF-TRICOM (National Cancer Institute/BN
      ImmunoTherapeutics Inc) and BiovaxID (Biovest International Inc) are highlighted.
      These data support the further development of such vaccines, and provide guidance
      for the development of improved agents and protocols for the use of therapeutic
      vaccination to treat cancer.

PMID- 20140812
TI  - Whole-cell vaccines: A failure or a success waiting to happen?
AB  - Whole-cell vaccination has demonstrated efficacy in small phase I and II clinical
      trials. However, in the past 3 years several high-profile phase III trials have
      failed to meet the predicted endpoints, including trials of the GVAX technologies
      (BioSante Pharmaceuticals Inc [formerly Cell Genesys Inc]) conducted by Cell
      Genesys. This review discusses the potential reasons for the failure of selected
      phase III trials and summarizes the current status of whole-cell vaccination,
      with specific reference to trials conducted in the past 2 years. Recently, new
      paradigms have emerged in the field of cancer vaccine research. In particular,
      the potential use of combination therapies that incorporate immune modulators and
      standard radio- and chemotherapy to synergize with whole-cell vaccines is
      discussed. In addition, key measures for improvements within the field that may
      be required for the generation of effective antitumor immunity are identified.

PMID- 20140813
TI  - Developing cell culture-derived pandemic vaccines.
AB  - The growing prospect of avian influenza viruses achieving sustained interhuman
      transmission, combined with the recent emergence of a novel swine-origin A/H1N1
      influenza strain, has brought the issue of influenza vaccine production capacity
      into sharp focus. It is becoming increasingly clear that traditional egg-based
      manufacturing processes may be insufficient to meet global vaccine demands in a
      pandemic situation that is caused by a highly pathogenic influenza virus. This
      review introduces the concepts of modern, cell culture-derived influenza vaccines
      and their manufacture, and explains the advantages of these vaccines in terms of
      both speed and efficiency of production as well as immunogenic efficacy. Vaccine
      production technologies using the mammalian cell lines Vero, MDCK and PER.C6, as
      well as the baculovirus/insect cell platform, are described in detail. Clinical
      data are provided from cell culture-derived vaccines that are at an advanced
      stage of development, and insights are provided into recent developments in the
      preclinical evaluation of more experimental technologies.

PMID- 20140814
TI  - Recent progress in dengue vaccine research and development.
AB  - Recent data suggest that dengue immunity could be elicited via either humoral or
      cell-mediated routes. Directing the immune response to serotype-specific epitopes
      from domain (D)III of the dengue virus envelope protein (Env) may induce
      effective levels of neutralizing antibodies. Removing serotype-crossreactive
      epitopes from DIII, as well as DII, may reduce the potential for the vaccine to
      induce non-neutralizing antibodies associated with antibody-dependent enhancement
      (ADE) of infection. The use of consensus Env DIII sequences for each serotype,
      and perhaps even a single consensus sequence for all four serotypes of dengue
      virus, may direct the immune response to invariant neutralizing sequences, which
      might improve vaccine safety and long-term efficacy. Vaccines incorporating
      capsid and/or non-structural (NS) proteins may be capable of inducing tetravalent
      cell-mediated immunity without ADE. However, the potential of cell-mediated
      immunity to contribute to pathology is not well understood, and modifications of
      NS proteins, such as truncated NS1, may be necessary for optimal vaccine safety.
      This review discusses recent progress in the development of dengue vaccines.

PMID- 20140815
TI  - Future paths for HIV vaccine research: Exploiting results from recent clinical
      trials and current scientific advances.
AB  - More than 60 million individuals have been infected with HIV and approximately
      half of these individuals have died since the epidemic started. The quest for an
      effective vaccine to prevent HIV transmission, which is likely to be the most
      effective approach to halt the epidemic, has been and continues to be an
      insurmountable challenge. Traditional vaccine strategies that have been effective
      for other vaccines have proven unsuccessful or impractical for HIV because of
      safety concerns. Nonetheless, substantial efforts have been directed at the
      development and clinical testing of HIV vaccines during the past two decades.
      Four major HIV vaccine efficacy trials conducted by VaxGen Inc (AIDSVAX 003 and
      AIDSVAX 004) and the NIH-supported HIV Vaccine Trials Network (HVTN 502 and HVTN
      503) failed to demonstrate efficacy; however, a recent trial conducted in
      Thailand (RV144 trial) demonstrated a low level of efficacy, resulting in some
      renewed optimism. Dissecting the causes for vaccine failure and, more
      importantly, for the partial level of efficacy observed in the RV144 trial should
      provide important guidance to the field. This review discusses the ongoing HIV
      vaccine trials and also highlights recent scientific advances that have provided
      the field with new leads to invigorate the search for effective vaccines.

PMID- 20140816
TI  - DNA fusion gene vaccines.
AB  - DNA vaccines are versatile and safe, but limited immunogenicity has prevented
      their use in the clinical setting. Experimentally, immunogenicity may be enhanced
      by the use of new delivery technologies, by coadministration of cytokines and
      pathogen-associated molecular patterns, or by fusion of antigens into molecular
      domains that enhance antigen presentation. More specifically, the immunogenicity
      of DNA vaccines may benefit from increased protein synthesis, increased T-cell
      help and MHC class I presentation, and the addition of a range of specific
      cytokines and pathogen-associated molecular patterns that increase activation of
      the innate immune system. Importantly, viral-vectored vaccines that act through
      the induction of one or more of these factors also may benefit from cytokine
      coadministration and increased antigen presentation. In order to increase
      immunogenicity to the level achieved with viral-vectored vaccines, various
      synergistic components may need to be incorporated into DNA vaccines. From the
      perspective of the future clinical use of DNA vaccines, it has been suggested
      that antigen presentation should be improved and cytokine coadministration
      attempted. However, even with these modifications, it is likely that the primary
      use of DNA vaccines may be as primers for viral-vectored vaccines, rather than as
      single agents. This review discusses the approaches used to enhance DNA vaccine
      immunogenicity, with a primary focus on fusion strategies that enhance antigen
      presentation.

PMID- 20140817
TI  - Adoptive cancer immunotherapy using genetically engineered designer T-cells:
      First steps into the clinic.
AB  - The treatment of patients with cancer using passive vaccination with antibodies
      has been demonstrated to be a promising option, particularly for 'soft tumors',
      most likely because of their greater accessibility compared with bulky solid
      tumors. While effector T-cells are efficient in the rejection of large organs and
      foreign tissues, the wide application of tumor-specific T-cells for cancer
      therapy has been limited by the inherent restriction of T-cell recognition to
      self antigens, and the difficulty in obtaining sufficient numbers of such cells
      with defined specificity. Advances in gene transfer and cell therapy have enabled
      the genetic modification of T-cells by the ectopic expression of predefined,
      specific receptor genes that redirect such 'designer cells' to any target of
      interest. This review discusses two approaches to applying redirected T-cells for
      adoptive cancer immunotherapy: the 'T-body' approach, which employs chimeric
      receptors with tumor-specific antibody-derived specificity, and the use of
      transgenes encoding tumor-specific T-cell receptors. Particular emphasis is
      placed on recent attempts using these approaches in the treatment of patients
      with cancer.

PMID- 20140818
TI  - Malaria vaccines - The long synthetic peptide approach: Technical and conceptual
      advancements.
AB  - This review describes the advances in malaria antigen discovery and vaccine
      development using the long synthetic peptide platforms that have been made
      available during the past 5 years. The most recent technical developments
      regarding peptide synthesis with the optimized production of large synthetic
      fragments are discussed. Clinical trials of long synthetic peptides are also
      reviewed. These trials demonstrated that long synthetic peptides are safe and
      immunogenic when formulated with various adjuvants. In addition, long synthetic
      peptides can elicit an antibody response in humans and have demonstrated
      inhibitory activity against parasite growth in vitro. Finally, new approaches to
      exploit the abundance of genomic data and the flexibility and speed of peptide
      synthesis are proposed.

PMID- 20140819
TI  - Therapeutic vaccines for prostate cancer.
AB  - Although androgen deprivation is the standard of care for advanced prostate
      cancer, patients with metastatic disease eventually progress to a castration
      resistant state. The available options for secondary therapy are hormonal therapy
      and chemotherapy. Significant potential remains for the development of
      alternative approaches, which can improve survival with early treatment but do
      not cause the toxicities associated with chemotherapy. The field of immunotherapy
      for prostate cancer has recently made significant progress, and data from several
      clinical trials demonstrating the efficacy of this type of therapy have been
      reported. These reports include data from randomized controlled trials with
      sipuleucel-T (Dendreon Corp) and with PROSTVAC-VF-TRICOM (NCI/BN
      ImmunoTherapeutics Inc), both of which resulted in improvements in overall
      survival in patients with advanced prostate cancer. Although these results are
      encouraging, there are many unresolved questions regarding immunotherapy,
      including the best clinical setting for immunotherapy, the definition of relevant
      clinical and immunological endpoints, and the potential combination of
      immunotherapies with other treatments. This review discusses the most promising
      recent developments in vaccine therapy for prostate cancer, as well as the
      challenges remaining to be addressed.

PMID- 20140820
TI  - Gene-based vaccines: Recent developments.
AB  - Gene-based vaccines are under development for a broad variety of applications,
      ranging from vaccines to immunotherapies for infectious diseases, cancer,
      autoimmune diseases and allergy. In addition, following the licensing of DNA
      vaccines for use in fish and horses, and DNA immunotherapy for the treatment of
      cancer in dogs, several veterinary uses of vaccines have been demonstrated for
      species ranging from fish and shrimp to cattle and horses. A variety of
      publications describing preclinical and clinical studies of the technologies used
      to increase the potency of gene-based vaccines, and research further elucidating
      the immune mechanisms involved have recently become available. This review
      discusses the progress and observations described in the recent literature,
      including a survey of the diseases and approaches that are being targeted with
      gene-based vaccines.

PMID- 20140821
TI  - Tanezumab, a recombinant humanized mAb against nerve growth factor for the
      treatment of acute and chronic pain.
AB  - Persistent pain represents a major health problem, and most current therapeutic
      approaches are associated with unwanted effects and unsatisfactory pain relief.
      Therefore, an urgent need exists to develop more effective drugs that are
      directed toward new molecular targets. Nerve growth factor (NGF) is involved in
      pain transduction mechanisms, playing a key role as a master switch in many
      chronic and inflammatory pain states; the NGF ligand and its receptor TrkA
      constitute well-validated targets for pain therapy. Tanezumab (RN-624), a first
      in-class recombinant humanized mAb targeting NGF, is being developed by Pfizer
      Inc for the potential treatment of pain associated with several conditions. In
      preclinical studies, tanezumab, and its murine precursor muMab-911, effectively
      targeted the NGF pathway in various chronic and inflammatory pain models. Phase I
      and II clinical trials in osteoarthritic pain and chronic lower back pain
      demonstrated good efficacy for the compound, as well as a good safety and
      tolerability profile. Given that tanezumab is an antibody, the drug demonstrates
      the general advantages of this class of products (including good specificity and
      favorable pharmacokinetics), and also appears to be particularly well suited for
      targeting the chronic and inflammatory-mediating pain actions of NGF and its
      receptor system.

PMID- 20140822
TI  - AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the
      potential treatment of cancer, including acute myeloid leukemia.
AB  - In development by Antisoma plc, AS-1411 is the first oligodeoxynucleotide aptamer
      to reach phase I and II clinical trials for the potential treatment of cancers,
      including acute myelogenous leukemia (AML). As an aptamer, AS-1411 does not
      appear to engage in hybridization-requiring pathways such as antisense effect,
      siRNA or triple helix formation. Instead, AS-1411 appears to bind to nucleolin
      specifically, and is subsequently internalized into the tumor cell. Nucleolin is
      an abundant protein, with expression that is correlated with the proliferative
      status of the cell: nucleolin levels are higher in tumors and actively dividing
      cells. Because of the multifunctional nature of nucleolin, it is probable that
      many secondary targets are affected following treatment with AS-1411. AS-1411 has
      demonstrated preclinical growth inhibition activity against a wide variety of
      tumor cell lines at concentrations in the micromolar range, and resulted in good
      efficacy in mice xenografted with tumor cells of human origin. In a phase I
      clinical trial in patients with advanced, refractory cancers with metastases at
      multiple sites, AS-1411 was safe and well tolerated; in addition, one complete
      response and one ongoing partial response were reported in two patients with
      renal cell carcinoma. A phase II trial of AS-1411 in combination with cytarabine
      in patients with AML demonstrated the combination to be superior to cytarabine
      alone. Thus, AS-1411 appears to be a promising candidate for cancer treatment in
      these pathologies. A greater understanding of the mechanism of action of this
      agent is essential to aid in future research.

PMID- 20140823
TI  - TRU-015, a fusion protein derived from an anti-CD20 antibody, for the treatment
      of rheumatoid arthritis.
AB  - TRU-015, being developed by Trubion Pharmaceuticals Inc and Pfizer Inc, is an
      intravenously administered anti-CD20 IgG fusion protein for the treatment of
      rheumatoid arthritis. TRU-015 depletes B-cells from the peripheral blood in
      vitro, and can mediate complement-and antibody-dependent cellular cytotoxicity.
      TRU-015 was well tolerated in patients with rheumatoid arthritis in phase I and
      II clinical trials, and demonstrated an efficacy profile similar to other
      biological agents approved for rheumatoid arthritis. At the time of publication,
      phase II trials were ongoing in patients with rheumatoid arthritis. TRU-015 could
      represent a novel therapy for the treatment of rheumatoid arthritis, although the
      efficacy, safety profile and advantages of this compound compared with existing
      therapeutic options would need to be established in phase III trials. In
      addition, this agent also may be useful to the treatment of B-cell neoplasms and
      autoimmune diseases.

PMID- 20140824
TI  - MVA-85A, a novel candidate booster vaccine for the prevention of tuberculosis in
      children and adults.
AB  - MVA-85A, in development by Oxford-Emergent Tuberculosis Consortium Ltd and the EU
      funded research program TB-VAC, is a live attenuated viral vaccine expressing the
      immunodominant tuberculosis (TB) antigen 85A, and is intended for use in a
      heterologous prime-boost strategy to prevent TB. MVA-85A is highly immunogenic in
      both animals and humans, eliciting strong polyfunctional CD4+ T-cell responses
      when administered as a boost following BCG vaccination or when administered to
      individuals previously exposed to TB. Animal studies have demonstrated trends
      toward reduced pathology and bacillary burden for animals vaccinated with BCG
      prime followed by MVA-85A boost compared with BCG alone; however, these positive
      effects appear to be modest, and interpretation is limited by the small number of
      animals tested. The vaccine has an excellent safety profile in BCG-naive,
      previously BCG-vaccinated and TB-exposed adults, as well as in BCG-vaccinated
      adolescents and children. At the time of publication, MVA-85A was in a more
      advanced stage of clinical development than other novel TB vaccine candidates,
      with a large-scale, proof-of-concept phase IIb clinical trial underway for the
      determination of safety, immunogenicity and prevention of TB in infants.

PMID- 20140825
TI  - Diagnostic accuracy of esophageal capsule endoscopy versus conventional upper
      digestive endoscopy for suspected esophageal squamous cell carcinoma.
AB  - BACKGROUND AND STUDY AIM: A video capsule similar to that used in small-bowel
      capsule endoscopy is now available for esophageal exploration. The aim of our
      study was to compare the accuracy of upper endoscopy (esophageal
      gastroduodenoscopy [EGE]) with esophageal capsule endoscopy (ECE) in patients at
      risk of esophageal squamous cell cancer (SCC). PATIENTS AND METHODS: 68 patients
      at risk of SCC secondary to a history of head and neck neoplasia were included in
      this comparison of techniques for detecting SCC and dysplasia. ECE was done using
      the first generation Pillcam ESO and EGE was performed in accordance with the
      usual practice of each center, followed by examination with 2 % Lugol staining
      and biopsy of unstained areas (39 neoplasia comprising 5 low grade dysplasia, 8
      high grade dysplasia and 26 SCC). RESULTS: Compared with EGE with and without
      Lugol staining, the sensitivities of ECE for neoplasia diagnosis were 46 % and 54
      %, respectively. On a per-patient basis, the sensitivity, specificity, and
      positive and negative predictive value of ECE were 63 %, 86 %, 77 % and 76 %,
      respectively, compared with EGE without staining, and 61 %, 86 %, 77 % and 73 %
      compared with EGE with iodine staining. Neither the ECE transit time nor the
      distance between the esopharyngeal line and the neoplastic lesion differed
      between the 21 false-negative and 18 true-positive cases diagnosed by ECE; the
      only difference was a smaller median diameter among false negatives ( P < 0.001).
      CONCLUSION: In a cohort at high risk for esophageal SCC, ECE is not sensitive
      enough to diagnose neoplastic lesions.

PMID- 20140826
TI  - Value of high-frequency miniprobes and conventional radial endoscopic ultrasound
      in the staging of early Barrett's carcinoma.
AB  - BACKGROUND AND AIMS: High-frequency miniprobes (HFPs) and conventional radial
      endoscopic ultrasonography (crEUS) are considered valuable tools in the staging
      of early Barrett's cancer. However, there is some controversy on whether HFPs are
      superior in the T staging of Barrett's cancer or whether the same level of
      accuracy can be achieved by the sole use of crEUS. PATIENTS AND METHODS: Patients
      referred for endoscopic treatment for Barrett's cancer were included in this
      prospective crossover trial and were randomly assigned to either HFPs or crEUS as
      the initial diagnostic method. Afterwards, all of the patients were re-examined
      with the alternative procedure. The staging results obtained with each method
      were documented prospectively. RESULTS: A total of 43 patients (median age 66
      years [interquartile range: 58 - 73]; 34-male) were included. A total of 23
      mucosal and 16 submucosal Barrett's cancers were confirmed at histology.
      Histological confirmation was not possible in four patients. Assessment of the T
      category was not possible with HFPs in 7 % of patients, compared with 33 % with
      crEUS ( P < 0.0001) due to positioning problems. T category was correctly
      assessed with HFP in 64 % of patients and with crEUS in 49 %. CONCLUSIONS: HFPs
      are significantly superior to crEUS for local staging of Barrett's cancer.
      However, the accuracy of assessment of the T category was unsatisfactory with
      both techniques.

PMID- 20140827
TI  - Risk of hemorrhagic gastropathy associated with colonoscopy bowel preparation
      using oral sodium phosphate solution.
AB  - BACKGROUND AND STUDY AIMS: Oral sodium phosphate (NaP) solution is widely used
      for colonoscopy bowel preparation and it may cause aphthous ulcers in the colon.
      Our aim was to evaluate whether oral NaP solution is associated with gastric
      mucosal lesions. METHODS: A total of 20 070 individuals underwent
      esophagogastroduodenoscopy (EGD) with colonoscopy, and 4271 individuals underwent
      EGD without colonoscopy, for cancer screening. Oral NaP solutions were used for
      bowel preparation prior to colonoscopy. Hemorrhagic gastropathy was graded using
      a five-point scale for erosive mucosal injury. The effect of NaP bowel
      preparation on hemorrhagic gastropathy was estimated using multiple logistic
      regression analysis with odds ratios (ORs) and 95 % confidence intervals (CIs).
      RESULTS: The incidence of hemorrhagic gastropathy was 1.6 % (70/4271) in the EGD
      only group and 4.0 % (809/20 070) in the EGD with colonoscopy group ( P < 0.001,
      unadjusted OR 2.55, 95 %CI 1.99 - 3.27). The ORs for mild (grade 1 - 2), moderate
      (grade 3), and severe (grade 4) hemorrhagic gastropathy according to NaP use were
      1.92 (95 %CI 1.45 - 2.54), 4.72 (95 %CI 2.65 - 8.47), and 5.99 (95 %CI 1.46 -
      24.63), respectively. After adjustment for confounding factors, NaP solution was
      a significant risk factor for acute hemorrhagic gastropathy in the multivariate
      analysis (OR 1.92, 95 %CI 1.34-2.74). In addition, male sex, a body mass index
      (kg/m (2)) of less than 20, concurrent use of antihypertensive or nonsteroidal
      anti-inflammatory drugs, and duodenal ulcers were independently associated with
      the development of hemorrhagic gastropathy. HELICOBACTER PYLORI infection and
      atrophic gastritis were negatively associated with hemorrhagic gastropathy.
      CONCLUSION: Oral NaP bowel preparation for colonoscopy was associated with
      hemorrhagic gastropathy.

PMID- 20140828
TI  - Differences in the prevalence of colorectal polyps in patients undergoing
      endoscopic removal of gastric adenoma or early gastric cancer and in healthy
      individuals.
AB  - BACKGROUND AND AIMS: We compared the prevalence of adenomatous and cancerous
      colon polyps in patients who underwent endoscopic removal of gastric neoplasms
      and in healthy controls. MATERIALS AND METHODS: This retrospective study reviewed
      the medical records of 186 patients with gastric neoplasms and 186 healthy
      subjects from January 2002 to October 2008. The gastric neoplasm group was
      comprised of patients undergoing endoscopic removal of gastric adenomas or early
      gastric cancers and serial fiberoptic colonoscopy (FCS) for checkups. The control
      group was comprised of subjects undergoing fiberoptic esophagogastroduodenoscopy
      (FEGD) and FCS for general checkup and was matched for age and sex with the
      gastric neoplasm group. Advanced colonic neoplasm was defined by any of the
      following: (1) the presence of three or more polyps; (2) polyp size at least 1.0
      cm; (3) high-grade dysplasia or adenocarcinoma confirmed by histopathologic
      examination. RESULTS: Of the 372 persons, colorectal polyps were detected in 124
      (33.3 %), advanced colonic neoplasms in 44 (11.8 %), and adenocarcinomas in 10
      (2.7 %). The overall prevalence of adenomatous or cancerous polyps ("all polyps")
      and the prevalence of advanced colonic neoplasms were significantly higher in the
      gastric neoplasm group than in the control group (all polyps: 40.9 % in the
      gastric neoplasm group vs. 25.8 % in the control group, P = 0.002; advanced
      colonic neoplasms: 15.6 % vs. 8.1 %, P = 0.025). The risk factors for all polyps
      were age, male sex, diabetes mellitus, and being assigned to the gastric neoplasm
      group, and those for advanced colonic neoplasms were age and being assigned to
      the gastric neoplasm group. Confining the analysis to the gastric neoplasm group,
      the risk factors for all polyps were identical with those for the total group;
      however, those for advanced colonic neoplasm were different (age vs. diabetes and
      hypertriglyceridemia). CONCLUSION: Endoscopists should consider performing
      routine FCS in patients undergoing endoscopic removal of gastric neoplasms.

PMID- 20140829
TI  - Diagnostic efficacy of ERCP in cholestatic infants and neonates--a retrospective
      study on a large series.
AB  - BACKGROUND AND STUDY AIMS: Cholestatic jaundice in infants is a serious
      condition, requiring timely and accurate diagnostic evaluation. Our aim was to
      determine the safety and diagnostic efficacy of endoscopic retrograde
      cholangiopancreatography (ERCP) in the diagnosis of cholestatic liver disease in
      neonates and infants. PATIENTS AND METHODS: ERCP procedures in cholestatic
      infants performed in our endoscopy unit between December 1998 and March 2008 were
      reviewed retrospectively (n = 104 children, 48 boys, 56 girls; mean age 7 weeks,
      range 3 - 25 weeks; mean weight 4.05 kg, range 1.5 - 4.8 kg). Endoscopic findings
      were compared with final diagnoses. Statistical analysis was performed and
      sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of
      ERCP were calculated both separately for each diagnosis and on aggregate.
      RESULTS: Cannulation of the papilla was successful in 95 of 104 patients (success
      rate 91.3 %). Biliary atresia of any type was found in 51 children (53.7 %), with
      a sensitivity of 86 %, a specificity of 94 %, a PPV of 96 %, and a NPV of 100 %.
      Choledochal cysts were found in seven children (7.4 %), with a sensitivity of 100
      %, a specificity of 90 %, PPV of 86 %, and NPV of 100 %. Biliary stones were
      found in seven patients (7.4 %). Other structural pathology was found in six
      patients, and no abnormality was seen in 24 patients. No severe complications
      occurred during or after ERCP. CONCLUSIONS: ERCP in cholestatic infants, when
      performed in an expert center, is a safe and reliable procedure that can detect
      biliary tract abnormalities (e. g. biliary atresia, bile duct stones or
      choledochal cysts) with high sensitivity and specificity. Laparotomies can be
      prevented in infants by demonstrating normal patency of the biliary tract by ERCP
      or by magnetic resonance cholangiography if improvements in this technique are
      made.

PMID- 20140830
TI  - Quality reporting of endoscopic diagnostic studies in gastrointestinal journals:
      where do we stand on the use of the STARD and CONSORT statements?
AB  - BACKGROUND AND STUDY AIMS: Many papers have been published in the field of
      diagnostic endoscopy in the last few years. However, there are no reports on
      their quality. The aim of this study was to evaluate quality in recently
      published endoscopic articles. MATERIALS AND METHODS: The study reviewed
      published articles on diagnostic endoscopy from 1998 to 2008. Quality was
      assessed and independently quantified by two observers using the STARD (STandards
      for the Reporting of Diagnostic accuracy studies) and CONSORT (Consolidated
      Standards for Reporting of Trials) statements. The interobserver proportion of
      agreement and kappa coefficient were estimated. RESULTS: A total of 120 articles
      comprising 10 randomized controlled trials and 110 diagnostic accuracy studies
      were evaluated. Most studies related to colonic polyp detection (30 %) or
      evaluation of Barrett's esophagus (29 %). Chromoscopy (45 %), fluorescence (21
      %), and narrow-band imaging (14 %) were the technologies most often evaluated.
      The mean number of items (i. e. standard requirements) fulfilled by the
      randomized controlled trials was 15.7 +/- 2.2 out of 22 while for the diagnostic
      accuracy studies it was 12.2 +/- 3.6 out of 25. Reporting of study results was
      complete in 90 % of the randomized controlled trials, but only 65 % of the
      diagnostic accuracy studies presented a cross-table of results. The global
      proportion of agreement between observers was 97 % in randomized controlled
      trials and 95 % in diagnostic accuracy studies. CONCLUSIONS: Recent publications
      in diagnostic endoscopy achieve only medium quality according to the available
      statements. It seems that it would be useful for authors, reviewers, and editors
      to be familiar with and apply these statements. The development of a specific
      checklist for diagnostic endoscopy publications might be helpful toward achieving
      better quality reporting in the future.

PMID- 20140831
TI  - The role of EUS for diagnosis of pancreatic cysts: observe, needle, or brush?

PMID- 20140832
TI  - The future of bariatrics: endoscopy, endoluminal surgery, and natural orifice
      transluminal endoscopic surgery.
AB  - This review considers the evolving role of endoscopic techniques in the treatment
      of obesity, and developments in minimally invasive procedures in endoscopy,
      endoluminal surgery and natural orifice transluminal endoscopic surgery (NOTES).
      Endoscopic approaches that are similar to surgery but less invasive, relying on
      gastric restriction and/or malabsorption, show some promise. Intragastric
      injection of botulinum toxin is also considered, as is the role of minimally
      invasive bariatric endoscopic interventions. Gastrointestinal stimulation with
      implanted electrodes may have potential in the treatment of obesity and
      endoscopic applications have a role to play in post-surgical interventions.
      Evolving research into endosurgical approaches is described. Current work on the
      feasibility of a NOTES approach to bariatric procedures is described.

PMID- 20140833
TI  - Colonic stenting: a palliative measure only or a bridge to surgery?
AB  - Self-expandable metal stents (SEMS) are used to relieve malignant luminal
      obstruction throughout the gastrointestinal tract. Colonic SEMS are used most
      often for palliation of obstruction in nonoperative candidates or in patients
      with advanced disease. The other indication for colonic stent placement is as a
      preoperative modality for the relief of acute obstruction so that resection can
      be done on an elective basis after stabilization of the acute illness and bowel
      preparation. For both of these indications, the goal is avoidance of a temporary
      or permanent ostomy. In this manuscript the supporting data for each of these
      indications will be reviewed.

PMID- 20140834
TI  - Endoscopic band ligation of rectal varices: a case series.

PMID- 20140836
TI  - Can we simplify terminology in the endoscopic treatment of superficial
      gastrointestinal neoplasia? Yes, we can.

PMID- 20140837
TI  - Biased assessment of 3D optical coherence tomography in a single post
      radiofrequency ablation patient without histological correlation.

PMID- 20140840
TI  - Misinterpretation of NSAID-induced Colopathy as Crohn's disease.
AB  - Although NSAID-induced colonopathy characterised by erosions, ulcers, strictures
      and diaphragms has been known for quite some time, it is not infrequently
      misinterpreted endoscopically and histologically as Crohn's disease. This is
      exemplified by the present case history of a 39-year-old man with bloody
      diarrhoea and a stenosis in the transverse colon that was histologically
      interpreted as "consistent with Crohn's disease". Treatment with glucocorticoids,
      however, merely gave rise to adverse reactions. After surgical treatment of the
      stenosis, the episodes of bloody diarrhoea persisted, and endoscopy continued to
      reveal erosions and ulcers in the transverse colon. Changing treatment to
      azathioprine also failed to produce any positive response, merely causing side
      effects. Subsequent evaluation of the histological specimens by a consultant
      pathologist turned up the tentative diagnosis of NSAID-induced colonopathy. An
      analysis of the patient's medical history revealed that he was suffering from
      Bechterew's disease, for which he had long been taking diclofenac. This case
      history is a good example of the fact that NSAID-induced enterocolopathy is still
      too poorly recognised among internists, gastroenterologists and pathologists,
      and, on the basis of the discontinuous endoscopic and histological findings, is
      often misinterpreted as Crohn's disease.

PMID- 20140841
TI  - Endoscopic sedation and monitoring practice in Germany: results from the first
      nationwide survey.
AB  - BACKGROUND AND AIMS: The use of sedation (e. g., of short-acting propofol) for
      gastrointestinal endoscopy has shown an upward trend in the United States and
      Europe over the last decade. This survey aimed at providing nationwide data on
      the current practice of endoscopic sedation and monitoring in Germany. METHODS: A
      21-item survey regarding current practices of endoscopy, sedation and monitoring
      in gastrointestinal endoscopy was sent to 3 802 members of the German Society of
      Digestive and Metabolic Diseases (DGVS). RESULTS: A total of 1 061 / 3 802 (28%)
      questionnaires were returned. The respondents performed an average of 28
      esophagogastro-duodenoscopies (EGDs) and 25 colonoscopies per week. Endoscopic
      procedures were staged in a hospital setting (60%) more often than in private
      practices (40%). The majority of the EGDs (74%) and colonoscopies (87%) were
      carried out under sedation, however, this fact may be influenced by a recall
      bias. The most frequently used agents for sedation were midazolam in 82% and
      propofol in 74% of the cases. The most common sedation regimens applied were
      propofol plus benzodiazepines (38%) and benzodiazepines with an opioid (35%).
      Patients were routinely monitored by pulse oximetry (97%), automated blood
      pressure readings (29%) and/or electrocardiography (13%). Supplemental oxygen was
      routinely administered in 34% of them. Endoscopists' satisfaction with sedation
      was greater among those using propofol than in the group applying benzodiazepines
      (visual analogue scale, 8.8 +/- 0.9 vs. 8.2 +/- 1.3, p < 0.0001). CONCLUSION:
      Besides the common administration of short-acting benzodiazepines, sedation with
      propofol is also gaining ground in Germany; it is applied mainly in low doses (up
      to 150 mg). German endoscopists are highly satisfied with these sedation
      regimens, with propofol significantly leading the score. Patient monitoring
      predominantly follows currently prevailing guidelines.

PMID- 20140842
TI  - What should be done with echoic splenic tumors incidentally found by ultrasound?
AB  - PURPOSE: The incidentally found primary intrasplenic tumor is mostly benign, but
      leads to a well known clinical problem: B-mode sonography, as well as computed
      tomography and MRI are often non-specific, and it is unclear whether a
      histological verification is warranted or a sonographic follow-up is justified.
      PATIENTS AND METHODS: etween October 2003 and October 2007 40 consecutive
      patients showed an echoic primary tumor of the spleen incidentally found by B
      mode ultrasound (US) and were included in this prospective study. All tumors were
      classified regarding size and echogenity. In all patients contrast-enhanced
      ultrasound (CEUS) was perfomed and tumor enhancement was characterized in
      comparison to normal splenic enhancement. Patients were followed up every 3
      months during the first year, and then once a year. RESULTS: Sizes of the lesions
      were < 3 cm in diameter in 28 (70 %), between 3 - 5 cm in 10 (25 %) and > 5 cm in
      2 (5 %) patients. Lesions were classified as predominantly hypoechoic (n = 27)
      and hyperechoic (n = 13) on B-mode US. During the arterial phase the lesions
      showed a hyperechoic (n = 12), isoechoic (n = 8), hypoechoic (n = 14), and
      anechoic (n = 6) enhancement on CEUS. Median follow was 24.8 months (range 3 - 48
      months). Lesions were constant in size (n = 34) or shrinking (n = 5). In one
      patient a new 5 mm lesion was seen during follow-up. This patient refused the
      splenectomy and follow-up was continued without further tumor growth. CONCLUSION:
      Echoic splenic tumors incidentally found by ultrasound can be managed by
      sonographic follow-up examinations.

PMID- 20140843
TI  - [CMV-enterocolitis as a cause for repeated intestinal intussusceptions in an
      adult patient after liver transplantation?].
AB  - Intestinal intussusception in the adult is often idiopathic but also known to be
      associated with chronic inflammatory bowel disease, coeliac disease, tumours or
      previous abdominal operations. A 22-year-old women after liver transplantation
      due to Crigler Najar Syndrome suffered from repeated episodes of abdominal pain.
      The diagnosis of repeated self-limited intestinal intussusceptions was made by
      computed tomography and ultrasonography. A laparoscopy revealed no cause for the
      intussusceptions. During a new episode of abdominal pain caused again by an
      intussusception a colonoscopy was performed that showed aspects of a discreet
      colitis. In the biopsies CMV was detected by qualitative PCR, while blood tests
      for CMV pp65 antigen were negative. A therapy with gancyclovir was initiated
      which lead to remission of the patient's symptoms. A colonoscopy six weeks later
      showed a completely normal colon, while in the biopsies CMV was not detectable.
      After a follow-up of one year the patient has not suffered from any further
      episodes. This case demonstrates the role of chronic intestinal CMV infection as
      a possible causative factor for repeated intussusceptions in immunosuppressed
      patients. Whenever possible a PCR for CMV in colon biopsies should be carried out
      to detect an intestinal CMV infection because as shown in our case results for
      immunohistopathology and CMV pp65 can be negative despite a chronic infection.

PMID- 20140844
TI  - [Exceptional bilocular inflammatory myofibroblastic pseudotumour (IMT)
      characterized by recurrent thoracic tumour growth and a rare (adult) second
      manifestation within the mesenteric tissue of the small intestine].
AB  - BACKGROUND: Despite its rare occurrence, inflammatory myofibroblastic
      pseudotumour (IMT) is relevant in the differential diagnosis of intestinal
      lesions. By the mean of an extraordinary case report, tumour site and specific
      characteristics, finding of the correct diagnosis, therapeutic management, and
      outcome of extrapulmonary IMT is decribed based also on relevant references from
      the literature. CASE REPORT: A 39-year old man experienced a multifocal thoracic
      recurrence and abdominal metastasis of IMT 12 years after successful primary
      resection of pulmonary IMT. The intra-abdominal lesion localised in the jejunal
      mesenteric tissue was removed surgically (resection status, R 0) by segmental
      resection of the mid-jejunum (length: 80 cm) followed by jejunojejunostomy.
      Histology evaluation confirmed IMT. Thoracic surgeons advised against a surgical
      approach to the pulmonary and thoracic lesions because of their number and
      proximity to the superior vena cava as well as mediastinal infiltration. Despite
      receiving repeated advice from his physicians, the patient has not agreed to
      combined immunosuppressive treatment with cyclophosphamide and steroids, because
      of his desire for children. He underwent 5 months of systemic steroid treatment,
      starting in the third postoperative month, which he then chose to stop because of
      Cushing symptomatology. He agreed to a computed tomography (CT) scan follow-up 12
      months after surgery, which revealed slight local progression of the remaining
      pulmonary lesion. Administration of a second steroid medication was initiated at
      a lower dose. No further CT scans were obtained. At present, he is consulting
      with an alternative medicine practitioner. CONCLUSION: This report documents a
      rarely described case of IMT at a jejunal mesenteric tumour site, interpreted as
      an uncommon late and extraordinary, metastatic, multifocal recurrence found 12
      years (!) after surgical resection of the primary pulmonary tumour.

PMID- 20140845
TI  - [Duodenal diverticulum--a therapeutic challenge].
AB  - We report the case of an 81-year-old women with a duodenal diverticular bleeding
      in the second portion of the duodenum. Various therapies are used to halt
      haemorrhaging in this tissue, including surgical or endoscopic intervention and
      transarterial embolisation. The lesion was identified and treated endoscopically
      with hypertonic saline solution and epinephrine. Because of a fistula and a
      continual bleeding we use a hemoclip two days later. The bleeding was completely
      controlled. However, a small mucosal defect was noted at the site where the
      hemoclip was applied, and an operation was necessary. Finally we discuss the
      therapy optoins based on a review of the literature.

PMID- 20140846
TI  - Glycaemic control is correlated with well-being index (WHO-5) in subjects with
      type 2 diabetes.
AB  - The aim of this study was to examine the potential correlation of WHO-5 well
      being index with glycaemic control and chronic complications in subjects with
      type 2 diabetes. The study included 156 subjects (73 men, mean age 64.05+/-9.11
      years, mean diabetes duration 12.22+/-5.61 years). Well-being was assessed by the
      WHO-5 score via a validated questionnaire comprising 5 questions (Q1-Q5). HbA
      (1c) showed a significant negative correlation with overall WHO-5 score (r (s)=
      0.248, p=0.002) and individual Q1-Q4 scores (r (s)=-0.262, p=0.001; r (s)=-0.248,
      p=0.002; r (s)=-0.207, p=0.009 and r (s)=-0.169, p=0.035 respectively). Subjects
      with adequate glycaemic control (HbA (1c) < 7%, n=67) had a significantly higher
      WHO-5 score in comparison to those with inadequate glycaemic control (HbA (1c)
      >or= 7%, n=89) (mean+/-SD: 19.69+/-5.47 vs. mean+/-SD: 17.11+/-6.38, p=0.011).
      Finally, WHO-5 score was significantly (p=0.013) lower in subjects with
      neuropathic pain than in those without neuropathic pain. CONCLUSIONS: In type 2
      diabetic subjects, glycaemic control shows a significant correlation with well
      being, while neuropathic pain is associated with lower well-being score.

PMID- 20140847
TI  - Genetic risk markers related to diabetes-associated autoantibodies in young
      patients with type 1 diabetes in berlin, Germany.
AB  - AIMS: To determine the prevalence of genetic risk markers of type 1 diabetes
      (T1D) in children diagnosed at a single centre in Germany and to assess their
      relation to diabetes-associated autoantibodies. METHODS: Blood samples from 243
      paediatric patients were genotyped for the high-risk HLA haplotypes DR3-DQ2
      (DQA1*05-DQB1*02) and DR4-DQ8 (DRB1*0401/2/4/5-DQB1*0302) and PTPN22 C1858 T
      polymorphism. The patients (51.4% male) were diagnosed with T1D at a median age
      of 8.6 y. The T1D-related autoantibodies GADA, IAA and IA-2A were analysed at
      diagnosis. RESULTS: 166 patients (68.6%) carried the DR3-DQ2, 114 (47.1%) the DR4
      DQ8 haplotype, while 41 (16.9%) patients were negative for both. The PTPN22 CC
      genotype was detected in 177 (72.8%), CT in 58 (23.9%) and TT in eight (3.3%)
      patients, respectively. The prevalence of T1D-related autoimmunity was 77.0% for
      IA-2A, 71.6% for GADA and 43.6% for IAA. There were no differences between
      patients with and without the 1858 T allele in terms of the frequency, levels or
      number of autoantibodies, but the former were younger at diagnosis than the
      latter (p=0.002), IA-2A were positively related to HLA DR4-DQ8 (p=0.004) and
      inversely associated with HLA DR3-DQ2 (p=0.002). GADA-positive patients were
      older than those without GADA (p=0.004). In multivariate logistic regression
      analysis including gender and age as confounding variables, DR4-DQ8 (OR 2.56,
      95%CI 1.35-4.86) and DR3-DQ2 (OR 0.36, 95%CI 0.19-0.68) were the only independent
      predictors of IA-2A positivity. CONCLUSION: The prevalence of genetic risk
      markers in Berlin children with T1D is found to be comparable to other Caucasian
      T1D populations. The presence of IA-2A at diagnosis is strongly associated with
      the HLA risk haplotypes, but not with PTPN22 polymorphism.

PMID- 20140848
TI  - Insulin signal transduction in normal cells and its role in carcinogenesis.
AB  - Convincing epidemiological evidence exists for a causal relationship between
      increased risk of cancer development and progression and type 2 diabetes mellitus
      as well as obesity. Though the underlying mechanisms remain elusive, in light of
      the well-described mitogenic actions of insulin, hyperinsulinaemia in the
      presence of insulin resistance is probably a key factor. In this short review, an
      overview over the insulin signalling cascade is given paying special attention to
      the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI
      3-K)/mammalian target of rapamycin (mTOR) pathways which are involved in protein
      synthesis and cell growth.

PMID- 20140849
TI  - Trends in the Management of Type 2 Diabetes and its Prescription Drug Costs in
      Greece (1998 & 2006).

PMID- 20140850
TI  - Genetic variation in the G-50T polymorphism of the cytochrome P450 epoxygenase
      CYP2J2 gene and the risk of younger onset type 2 diabetes among Chinese
      population: potential interaction with body mass index and family history.
AB  - BACKGROUND: Cytochrome P450 (CYP) 2J2 is a regulatory enzyme in the biosynthesis
      of biologically active CIS-epoxyeicosatrienoic acids (EETs). EETs have been
      suggested to modulate PPAR-gamma and PPAR-alpha transcription activity and play a
      role in stimulus-secretion coupling in pancreatic beta cells. Genetic
      abnormalities in the expression of CYP2J enzymes may play a role in the
      pathogenesis of type 2 diabetes mellitus (T2DM). Our objective was to investigate
      CYP2J2 G-50T polymorphism (rs890293) in association with insulin resistance
      markers and T2DM in a Chinese population. METHODS: A total of 1 747 Chinese T2DM
      patients and 994 non-diabetic subjects were studied. The CYP2J2 G-50T
      polymorphism was determined by a restriction fragment-length polymorphism
      polymerase chain reaction. RESULTS: Neither the CYP2J2 genotype distribution nor
      allele frequency differed between the control subjects and the T2DM patients.
      However, among diabetics, subjects with a younger age at diagnosis (AAD; <40
      years) had significantly higher T variant frequency than those with an AAD>/=40
      years. When diabetic patients were stratified by their AAD in 10-year intervals,
      the trend was significantly linear among age grades. A significant interaction
      between the CYP2J2 T variant and younger onset diabetic subjects with positive
      family diabetes history, and BMI>/=27 kg/m (2) were observed to have the highest
      risk of diabetes and younger onset diabetics with the T variant had higher
      homeostasis model assessment estimate of insulin resistance (HOMA-IR) and HOMA
      beta values than their GG genotype counterparts. Plasma concentrations of stable
      EET metabolites were significantly lower in individuals with the G-50T SNP in
      younger onset diabetics. CONCLUSION: These data suggest that age of onset, family
      history, and obesity may modify the association between the CYP2J2 G-50T
      polymorphism and T2DM risk. CYP2J2 G-50T polymorphism may contribute to the
      pathogenesis of T2DM, partially by effects on insulin resistance, in patients
      with younger onset T2DM.

PMID- 20140851
TI  - Follow-up of adolescents with diabetes after transition from paediatric to adult
      care: results of a 10-year prospective study.
AB  - OBJECTIVE: Our main objective in this study was to identify the type of clinical
      care received by young type 1 diabetic patients who have made the transition from
      paediatric to adult care, and to assess the metabolic status of long-term
      treatment after the transition. METHODS: A standardized questionnaire was used
      prospectively to follow 99 patients with type 1 diabetes mellitus after their
      transition to adult care. This survey was done once a year, from 1998 to 2008.
      RESULTS: Directly after transition from paediatric care 38.4% of patients were
      found at specialised outpatient units; whereas 41.1% received care at a diabetes
      centre and 20.5% were monitored by general practitioners or specialists in
      internal medicine. Five-year results showed that 25.0% had continued to visit an
      outpatient unit; 41.7% were still visiting a diabetes centre; and 33.3% had
      remained in the care of general practitioners or internal specialists. We
      observed a trend showing slight improvements in the HbA1c values over time,
      however no major changes in metabolic control were observed after transition.
      CONCLUSIONS: Transition marks a critical phase for young, diabetic patients as
      they may frequently switch from one physician or centre to another. The
      individual optimization of therapy, established during paediatric care, provides
      the decisive groundwork for disease control in young adults.

PMID- 20140852
TI  - Direct costs for care and glycaemic control in patients with type 2 diabetes in
      Sudan.
AB  - The aim of this study was to estimate the contribution by type 2 diabetic
      patients in a low-income country from their own income in attempting to control
      the disease and to prevent chronic diabetes complications through good glycaemic
      control. Socio-economic and demographic data for study subjects were obtained
      from 822 adult diabetic patients attending public or private diabetic clinics in
      Khartoum State, Sudan. The average annual income of diabetic patients was
      estimated as USD 1.923. The direct cost of diabetes control was USD 175 per year.
      This included cost of drugs and ambulatory care, although drug supply was
      insufficient for 52% of the patients. Glycosylated hemoglobin as a measure of
      glycaemic control was determined to be unsatisfactory in 77% of patients. This
      gives an immediate indication that current practices in diabetes control in urban
      Sudan are not cost-effective. Patients attending private clinics had a higher
      income and cost of diabetes control than those attending public clinics. However,
      both groups had similar proportion of poor glycaemic control, which reflects the
      insufficient care given to diabetic patients, mainly due to deficient resources
      and inefficient utilization of what is scarcely available.

PMID- 20140853
TI  - [Why patients lose weight after bariatric operations].
AB  - The obesity epidemic is in Germany as well as worldwide a major health problem
      which is associated with increased morbidity and mortality. Bariatric surgery is
      currently the most effective therapy for significant and sustained weight loss.
      The most common form of bariatric surgery worldwide is Roux-en-Y gastric bypass
      surgery. The underlying mechanisms behind the superiority of this procedure are
      unclear and remain to be elucidated, but recent findings suggest that
      gastrointestinal hormones play an important role rather than malabsorption or
      restriction. It appears that gastric bypass surgery alters the physiology of
      weight regulation and eating behaviour in patients who have undergone the
      procedure. Gastrointestinal hormones have recently been found to be an important
      element in the physiology of appetite regulation due to the signals from the
      periphery to the brain. It is the purpose of this article to review the current
      knowledge about the regulation of body weight and eating behaviour by
      gastrointestinal hormones and how their levels are altered after bariatric
      surgery.

PMID- 20140854
TI  - CT features of foreign body granulomas after cosmetic paraffin injection into the
      cervicofacial area.
AB  - PURPOSE: Cosmetic injection of paraffin into cervicofacial tissues has been
      practiced in the past, especially in Asia, resulting in foreign body granuloma
      (paraffinoma). The purpose of this study was to describe the computed tomography
      (CT) findings of cervicofacial paraffinomas. MATERIALS AND METHODS: CT images of
      5 patients (4 women and 1 man; age range, 54-80 years; mean age, 67.6 years), who
      had received direct paraffin injections into cervicofacial tissues, were reviewed
      retrospectively. RESULTS: The lesions were bilateral and located in the
      subcutaneous fat layer of the cheek (n = 5), buccal space (n = 2), periorbital
      area (n = 1), periauricular area (n = 1), neck (n = 1), and nose (n = 1). The
      predominant CT features were speckled mass formation (n = 3), fat-density nodule
      (n = 5), high-density nodule (n = 5), nodular calcification (n = 5), and rim
      calcification (n = 4). CONCLUSION: Paraffinomas in the cervicofacial region have
      specific CT features that are distinct from other soft tissue masses.

PMID- 20140855
TI  - Conventional and diffusion-weighted MRI of extrahepatic hydatid cysts.
AB  - PURPOSE: To evaluate the value of conventional and diffusion-weighted (DW)
      magnetic resonance imaging (MRI) in the diagnosis of extrahepatic hydatid cysts.
      MATERIALS AND METHODS: Forty-one extrahepatic hydatid cysts (12 renal, 6
      pulmonary, 5 peritoneal, 4 bone, 3 soft tissue, 3 pancreatic, 2 splenic, 2
      retroperitoneal, 1 adrenal, 1 scrotal, 1 diaphragmatic, and 1 cardiac) were
      included in this retrospective study. After a series of routine conventional MRI,
      DW imaging was performed using a breath-hold, single-shot, echo-planar, spin echo
      sequence with three b factors (0, 500 and 1,000 s/mm(2)), and apparent diffusion
      coefficient (ADC) maps were created. On DW trace images, signal intensity of the
      cysts was visually compared to the signal intensity of the muscle with the use of
      a 3-point scale: 0, isointense; 1, moderately hyperintense; 2, significantly
      hyperintense. For quantitative evaluation, signal intensity ratio and ADC of the
      cystic lesions were calculated. RESULTS: On conventional MR images, all but 3
      patients had concomitant liver involvement. Three of them were disseminated. On
      DW trace images (b = 1,000 s/mm(2)), most hydatid cysts (86%) were hyperintense,
      while five hydatid cysts (14%) were isointense. Quantitatively, the mean ADC of
      the hydatid cysts was 2.8 x 10(-3) +/- 0.5 mm(2)/s. CONCLUSION: DW imaging may
      help in the differential diagnosis of extrahepatic hydatid cysts.

PMID- 20140856
TI  - The role of diffusion-weighted echo planar MRI in central nervous system
      infections regarding etiopathogeneses.
AB  - Neuroimaging constitutes an important component in the diagnosis of the
      underlying infectious agents in central nervous system (CNS) infections. Despite
      the recent advances in neuroimaging evaluation, the diagnosis of unclear
      infectious CNS diseases remains a challenge. Conventional magnetic resonance
      imaging (MRI) is used in routine practice to identify abnormal areas involved in
      CNS infections. More recent MRI techniques, such as diffusion-weighted imaging
      (DWI), provide additional helpful information in the assessment of CNS infectious
      lesions compared with conventional MRI. This pictorial essay summarizes the
      clinical role of DWI in the demonstration of CNS infections including meningitis,
      encephalitis and pyogenic infections, and determination of the lesions compared
      with conventional MRI on the basis of physiopathologic phases of the infections.

PMID- 20140857
TI  - Thrombolysis during the endovascular treatment of iliac artery occlusions.
AB  - PURPOSE: The purpose of this study was to assess the possible therapeutic
      advantage of thrombolysis prior to recanalization of iliac occlusions with
      percutaneous treatment angioplasty and stenting. MATERIALS AND METHODS: We
      retrospectively studied 28 cases of iliac occlusions in 26 patients, occurring
      over a six-year period. All patients suffered from claudication. Percutaneous
      treatments were performed using thrombolysis in 25 cases. The average duration of
      the infusion with urokinase-type plasminogen activator was 28.2 hours (range, 9
      48 hours); total dose was 1,820,000 units per hour. The average duration of the
      follow-up was 46.6 months (range, 2-81 months). RESULTS: In 21 of 25 cases (84%),
      we managed to correctly pass through the iliac occlusion using a guidewire and
      completed the thrombolysis. In all these cases, thrombolysis caused the complete
      dissolution of thrombi. All 21 cases with complete thrombolytic treatment had
      complete recanalization of the iliac axis. Twenty of these 21 cases (95%) were
      than successfully treated with percutaneous methodologies. CONCLUSION:
      Thrombolysis may give an advantage in approaching the percutaneous treatment of
      atherosclerotic iliac arterial occlusions.

PMID- 20140858
TI  - [Generation of factor VIII gene knockout mouse by tetraploid embryo
      complementation technology].
AB  - OBJECTIVE: Factor VIII( FVIII) gene knockout mouse model was established for
      further study on the treatment of hemophilia A. METHODS: Exons 16-19 of the mouse
      FVIII gene were knocked out by ET clone, ES homologous recombination and
      tetraploid embryo compensation technology. PCR, reverse transcriptase-PCR(RT-PCR)
      and immunohistochemistry were used to detect the transcription and translation
      pattern of FVIII. The phenotype of the knockout mice was analyzed by examining
      the activated partial thromboplastin time (APTT) and FVIII activity (FVIII:C).
      RESULTS: PCR, RT-PCR and immunohistochemistry confirmed that FVIII was deficient
      in the FVIII gene knockout mouse. The APTT results showed that FVIII-deficient
      mouse plasma had a prolonged clotting time compared to normal mouse plasma. The
      FVIII:C in heterozygous, hemizygous and homozygous mice was 80%, 8% and 10% of
      that in normal mice, respectively. CONCLUSION: The phenotype of the FVIII gene
      knockout mouse appears grossly similar to that of human with hemophilia A.
      Establishment of this model may promote the development of new technologies of
      treatment to hemophilia A.

PMID- 20140859
TI  - [Mutation spectrum of phenylalanine hydroxylase gene in patients with
      phenylketonuria in Tianjin and surrounding areas of Northern China].
AB  - OBJECTIVE: To investigate the characteristics of the phenylalanine hydroxylase
      (PAH) gene mutations in patients with phenylketonuria (PKU) in Tianjin and
      surrounding area, in order to provide basic information for genetic counseling
      and prenatal gene diagnosis. METHODS: All of the 13 exons and flanking introns of
      the PAH gene from 99 patients with PKU were amplified by polymerase chain
      reaction and analyzed by single strand conformation polymorphism (SSCP),
      denaturing high performance liquid chromatography (DHPLC) and DNA sequencing.
      RESULTS: Mutations were found in all exons or flanking introns of the PAH gene
      except for exons 9 and 13. A total of 41 different mutations were identified
      which corresponded to 93.94% (186/198) of the PAH alleles, including 22 missense
      mutations (53.6%), 7 nonsense mutations (17.1%), 9 splicing junction
      mutations(22.0%), and 3 deletion mutations (7.3%). Six novel mutations (IVS3nt+1g
      -> a, A165D, Q301X, G344D, P362L and R413G) were identified and another 6
      mutations (S16fsdelCT, R71H, IVS5nt+1g--> a, G239S, R243X and R261X) were
      reported in Chinese population for the first time according to the databases from
      http://www.pahdb.mcgill.ca. The most common mutations included 243Q
      (36/198,18.18%), V399V (22/198, 11.1%), R111X (19/198, 9.6%), E6nt-96A--> g
      (18/198, 9.1%), R413P (15/198, 7.6%) and Y356X (13/198, 6.6%). In addition, 4
      silent mutations (except V399V) in exons and 8 variations in introns were found
      in this study. The IVS1nt+40t--> g and IVS10nt-31g--> a were confirmed as novel
      variations by international PAH databases and IVS5nt-54g--> a was the first
      report in China. CONCLUSION: The frequencies of six common mutations were close
      to that in Beijing area of China, but it was different in sequence. The extensive
      mutation spectrum of the PAH gene showed higher heterogeneity in Tianjin and
      surrounding areas of Northern China comparing with other reports. According to
      this report, exons 7 and 11 are the hot spots and should be detected first for
      PAH gene quick diagnosis in this area, then comes exons 3, 6 and 12, and finally
      exons 5, 10 and others.

PMID- 20140860
TI  - [Clinical, molecular pathological and genetic analyses of a Chinese family with
      congenital muscular dystrophy type 1A].
AB  - OBJECTIVE: To analyze and characterize the clinical, molecular pathological and
      genetic features of a Chinese family with congenital muscular dystrophy type 1A
      (MDC1A). METHODS: Clinical data of the proband and her family members were
      collected. Immunohistochemistry staining was performed on muscular biopsy tissues
      with anti-merosin, alpha-dystroglycan, beta-dystroglycan and dystrophin
      antibodies. Genomic DNAs from the patient and her parents were extracted using
      standard procedures from the peripheral blood leukocytes. PCR and DNA direct
      sequencing were employed to analyze all of the 65 exons of the LAMA2 gene to
      determine the gene mutation, and the relationships between genotype and phenotype
      were analyzed. RESULTS: The proband presented with delayed motor development and
      a myopathic face. Her midrange elevated serum creatine kinase (CK) levels and
      white matter signal intensity changes are consistent with MDC1A, and was
      clinically diagnosed as MDC1A. The immunohistochemistry analysis for the proband
      exhibited complete loss of merosin staining. Further test with PCR detected a
      homozygous mutation of c.817A>T in exon 5, while her parents were heterozygotes
      for the mutation. CONCLUSION: The authors have defined the clinical manifestation
      of the Chinese family with MDC1A. The proband carried a homozygous nonsense
      mutation c.817A>T, and her parents were heterozygous carriers, consistent with
      autosomal recessive inheritance.

PMID- 20140861
TI  - [Autoimmune regulator gene mutations in a Chinese family with autoimmune
      polyendocrinopathy syndrome type I].
AB  - OBJECTIVE: To identify the mutation of the autoimmune regulator gene (AIRE) in a
      Chinese family with autoimmune polyendocrinopathy syndrome type I (APS-I).
      METHODS: The AIRE gene mutations were detected using PCR and direct DNA
      sequencing. Restriction enzyme analysis was used to confirm the mutations and
      bioinformatic methods were used to predict the possible impact of the mutations
      on the structure and function of the AIRE protein. RESULTS: A compound
      heterozygous mutation of A19T/R257X was detected in the proband. Her father had
      the A19T mutation in exon 1, but this mutation was not detected in 100 unrelated
      healthy individuals. Her mother had the R257X mutation in exon 6. CONCLUSION:
      This is the first report about AIRE mutations in Chinese APS-I kindred. The A19T
      mutation identified in this study has not been reported in the human gene
      mutation database (HGMD); the R257X has not been reported in Asians.

PMID- 20140862
TI  - [Polyglutamine-expanded ataxin-3 is degraded by autophagy].
AB  - OBJECTIVE: To investigate the role of autophagy on the pathogenesis of
      spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD). METHODS: HEK293 cells
      expressing polyglutamine-expanded ataxin-3 were used as cell model for SCA3/MJD.
      The level of polyglutamine-expanded ataxin-3 was detected after cells were
      treated with different inhibitors or inducer of autophagy. RESULTS: Inhibition of
      autophagy increased aggregate formation and cell death in HEK293 cells expressing
      mutated ataxin-3, and vice versa. CONCLUSION: The data suggested that autophagy
      is involved in the degradation of mutant ataxin-3, resulting in a decrease in the
      proportions of aggregate-containing cells and cell death in HEK293 cells
      expressing polyglutamine-expanded ataxin-3. It is possible that autophagy may be
      applied as a potential therapeutic approach for SCA3/MJD.

PMID- 20140863
TI  - [Association between the regulator of G-protein signaling 2 gene 1891-1892del TC
      polymorphism with hypertension in Xinjiang Kazakh population].
AB  - OBJECTIVE: To investigate the association of the 1891-1892del TC polymorphism of
      regulator of G-protein signalling 2 (RGS2) gene with hypertension in Xinjiang
      Kazakh population. METHODS: The case-control study was performed in 444 cases and
      489 controls. The genotypes of the individuals in the 1891-1892del TC locus were
      identified by TaqMan method. RESULTS: A significant association was observed
      between the1891-1892TC insertion/deletion polymorphism with hypertension in men
      (OR=1.698, P=0.03) and in the total population (OR=1.32, P=0.044). The mean
      systolic blood pressure and serum uric acid levels of the ID+DD carriers were
      significantly higher than that of the II carriers (adjusted, P=0.04 and P<0.01).
      CONCLUSION: The results suggest that the D allele of the 1891-1892TC
      insertion/deletion locus of the RGS2 gene might be an independent risk factor for
      hypertension in Xinjiang Kazakhs; and the polymorphism may have some influence on
      serum uric acid level in this population.

PMID- 20140864
TI  - [A clinical and laboratory study on acute myeloid leukemia with t(6;9)(p23;q34)].
AB  - OBJECTIVE: To explore the clinical and laboratory features of 6 cases of acute
      myeloid leukemia (AML) with t(6;9)(p23;q34). METHODS: Chromosome preparation of
      bone marrow cells was performed with regular method. R-banding by heating using
      Giemsa banding technique (RHG) was used for karyotype analysis. The immunoprofile
      was studied by flow cytometry (FCM) using a panel of monoclonal antibodies.
      Chromosome painting was performed by using whole chromosome paint probes for
      chromosomes 6 and 9 in all the 6 cases. The expression of fusion gene DEK/CAN and
      FLT3-ITD mutation were analyzed by reverse transcription-PCR(RT-PCR). RESULTS:
      The t(6;9)(p23;q34) was found in all the 6 cases including 4 cases of M2 and 2
      cases of M4. Blast cells were positive for CD13 and CD33 in 6 patients, for HLA
      DR in 4 patients, for CD34 and CD117 in 3 cases, for CD38 or CD15 each in 1 case,
      respectively. A reciprocal translocation between chromosome 6 and 9 was confirmed
      by chromosome painting technique in the 6 cases. The DEK/CAN fusion gene was
      found in all the 6 cases, FLT3-ITD mutation was detected in three of them. Follow
      up showed that 3 patients died with a survival time of 3 months, 5 months and 6
      months, respectively. The other three obtained complete remission and are still
      alive. CONCLUSION: The t(6;9)(p23;q34) is a rare recurrent abnormity. AML with
      t(6;9)(p23;q34) has unique clinical and laboratory features and its prognosis is
      poor in most cases.

PMID- 20140865
TI  - [Studies on the molecular diagnosis and prenatal diagnosis of the spinal muscular
      atrophy carriers by multiplex ligation-dependent probe].
AB  - OBJECTIVE: To study the application of the multiplex ligation-dependent probe
      amplification (MLPA) method in genetic and prenatal diagnosis for spinal muscular
      atrophy (SMA). METHODS: Four patients, 16 parents and 4 fetuses from 8 SMA
      pedigrees were included. MLPA was performed for molecular analysis, and
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was
      used for the mutation detection of the 4 patients. RESULTS: For all the four
      patients, the same homozygous deletion of the exons 7 and 8 of the survival motor
      neuron 1 (SMN1) gene, was detected by PCR-RFLP and MLPA. All fourteen parents
      from the 8 pedigrees were carriers of the SMN1 gene heterozygous deletion, except
      the mothers in pedigrees 1 and 4 in whom the mutations were different.
      CONCLUSION: MLPA is a simple and efficient quantitative method for copy number
      analysis of the SMN genes. It can be used for the genetic diagnosis and prenatal
      diagnosis of the SMA patients and carriers.

PMID- 20140866
TI  - [Evaluation of the fidelity of multiple displacement amplification from small
      number of cells].
AB  - OBJECTIVE: To evaluate the fidelity of multiple displacement amplification (MDA)
      from small number of cells (1-10 cells) by 10K 2.0 SNP mapping array. METHODS: A
      fibroblast cell line (Tri-18; GM02732, 47, XY, +18) was used as the template, and
      6 groups were set up in the study. Groups A and B were positive and negative
      control, respectively; groups C-F were experimental groups involving the MDA
      products from 1, 2, 5 and 10 cells respectively. In combination of single
      nucleotide polymorphism (SNP) array, the product of each group was assessed based
      on the genome coverage, loss of heterozygosity (LOH) rate and allele dropout
      (ADO) rate. RESULTS: The nonspecific product of negative control presented an
      average call rate of 3.2%. The genome coverage of the MDA product increased from
      86.4% to 96.4% with the increasing number of template from 1 to 10 cells, while
      the LOH rate and ADO rate decreased significantly (P<0.05). CONCLUSION: MDA is a
      highly efficient and reliable method for whole genome amplification. The fidelity
      of MDA will be improved significantly with the increasing number of template
      cells. 10K 2.0 SNP mapping array is a quick, accurate and comprehensive method to
      evaluate the fidelity of amplified DNA products, but the ADO SNPs should be
      distinguished from those of preferential amplification from the LOH loci to avoid
      errors.

PMID- 20140867
TI  - [Application of array-based comparative genomic hybridization in precise
      diagnosis of unbalanced chromosome aberration].
AB  - OBJECTIVE: To evaluate the method of array-based comparative genomic
      hybridization (array-CGH) in identifying unbalanced chromosome aberrations.
      METHODS: Four cases that could not be diagnosed by conventional cytogenetic
      technique were selected to undergo array-CGH analysis. DNA samples were extracted
      and hybridized with the Affymetrix SNP 6.0 arrays using Human Mapping SNP6.0
      assay kit following the manufacturer's standard protocol. The data were analyzed
      by two professional software packages, GCOS and Genotyping Console. RESULTS: By
      using array-CGH technique, all the four cases were diagnosed precisely through
      identifying two duplications and two complex derivative chromosomes. CONCLUSION:
      Array-CGH is an effective method for whole-genome identification of unbalanced
      chromosomal aberrations with high sensitivity and specificity. It has a great
      value to investigate the correlations between genotype and phenotype in clinical
      service, especially in prenatal diagnosis.

PMID- 20140868
TI  - [Histone deacetylase inhibitors as therapeutic agents for polyglutamine
      disorders].
AB  - During the past few years, gene expression studies have shown that the
      perturbation of transcription frequently results in neuronal dysfunction in
      polyglutamine (PolyQ) diseases such as Huntington's disease (HD). Histone
      deacetylases (HDACs) act as repressors of transcription through interaction with
      co-repressor complexes, leading to chromatin remodelling. Aberrant interaction
      between PolyQ proteins and regulators of transcription could be one mechanism by
      which transcriptional dysregulation occurs. Here, the authors discuss the
      possible mechanism of transcriptional dysfunction in PolyQ disease, including the
      effect of histone acetyltransferases (HATs) and HDACs on pathogenesis, and the
      potential therapeutic pathways through which histone deacetylase inhibitors
      (HDACIs) might act to correct the aberrant transcription observed in HD and other
      PolyQ diseases.

PMID- 20140869
TI  - [Current research advances of the relationship between non-coding RNAs and
      tumor].
AB  - Non-coding RNAs (ncRNAs) are RNA molecules that exclude mRNA, tRNA and rRNA, and
      do not code proteins. ncRNAs play a various roles in the regulation of important
      vital activities in many organisms such as bacteria, fungi and mammals. Recent
      researches have shown that ncRNAs, as oncogenes or tumor suppressor genes, have
      tremendous impacts on the occurrence and development of tumors. Meanwhile, ncRNAs
      have become a new type of tumor markers and new targets for cancer treatment.
      This review describes the research progresses of ncRNAs such as small
      interference RNA and microRNA, and their roles in carcinogenesis.

PMID- 20140870
TI  - [Analysis of the P53 transcriptional activity in gastric cancer].
AB  - OBJECTIVE: To investigate the transcriptional activity of P53 in gastric cancer.
      METHODS: The activity of p53 in gastric cancer was investigated by dual
      luciferase reporter assay. The coding sequence of the p53 was amplified by
      reverse transcription-polymerase chain reaction (RT-PCR) and sequenced. The
      expression of P21WAF1/Cip1, Gadd45alpha and Mdm2 was detected by
      immunohistochemistry in 76 samples of gastric carcinoma, and their adjacent
      tissues were analyzed as control. RESULTS: The p53 activity was higher in human
      normal cell lines than that of gastric cancer. Furthermore, the transcriptional
      activity of P53 was lowest in MKN28 cells in which p53 was mutated. The
      expression level of P21WAF1/Cip1, Gadd45alpha and Mdm2 in the adjacent tissues
      was higher than that of cancer tissues (P<0.05), and there was a tendency of
      decline in the positive ratio with the poor differentiation of the carcinoma
      (P<0.05). In addition, a strong linear correlation was observed between
      P21WAF1/Cip1, Gadd45alpha and Mdm2 (P<0.05). CONCLUSION: Changes of P53
      transcriptional activity play an important role in the development of gastric
      cancer. p53 mutation could affect its transcriptional activity. P21WAF1/Cip1,
      Gadd45alpha and Mdm2 are a group of effecters that could reflect P53
      transcriptional activity when detected together in cancer tissues.

PMID- 20140871
TI  - [The 521 T--> C mutation in the keratin 6A gene in a pedigree with pachyonychia
      congenita type I].
AB  - OBJECTIVE: To identify the mutation in the keratin 6A(K6A) gene in a pedigree
      with pachyonychia congenita type I (PC-I). METHODS: Blood samples were obtained
      from 2 affected, 3 unaffected members in this family, and 100 unrelated healthy
      individuals. Mutation detection was carried out by PCR amplification of the K6A
      gene and direct DNA sequencing. RESULTS: A heterozygous mutation of T--> C
      transition at position 521 in exon 1 of the K6A gene was found in the 2 affected,
      but not in the unaffected members and 100 unrelated healthy individuals.
      CONCLUSION: The mutation of 521T--> C in the K6A gene is the disease causing
      mutation in this PC-I family.

PMID- 20140872
TI  - [Expression of the NYGGF4 gene during human preadipocyte differentiation and the
      regulative role of tumor necrosis factor-alpha].
AB  - OBJECTIVE: To observe the changes of NYGGF4 gene expression during human
      preadipocyte differentiation and to explore the regulative role of tumor necrosis
      factor alpha (TNFalpha) on NYGGF4 gene expression in matured human adipocytes.
      METHODS: Human preadipocytes-visceral (HPA-v) were cultured in vitro and
      differentiated into the matured adipocytes. Fully differentiated adipocytes were
      treated with TNFalpha in different concentrations for 16 hours or at 10 ng/mL for
      various times. Levels of the NYGGF4 mRNA were evaluated by real-time reverse
      transcription-PCR(RT-PCR). RESULTS: (1) After induction of differentiation, more
      than 90% of the HPAs-v exhibited typical adipocyte morphology on the 17th day.
      (2) In human preadipocytes, the level of NYGGF4 mRNA expression remained low. The
      NYGGF4 mRNA level was gradually increased with the preadipocytes being
      differentiated into the matured adipocytes, and reached the highest level in the
      fully differentiated adipocytes. (3) Treatment of the human matured adipocytes
      with TNFalpha resulted in a significant increase in the level of NYGGF4 mRNA. The
      up-regulatory effect of TNFalpha on the NYGGF4 gene expression tended to be
      enhanced with the increasing concentrations and elongation of time. CONCLUSION:
      During human preadipocytes differentiation, the level of NYGGF4 gene mRNA
      expression increases gradually. TNFalpha could upregulate the expression of
      NYGGF4 mRNA in human matured adipocytes. The regulatory effect of TNFalpha on the
      NYGGF4 gene expression is of dose-dependent and time-correlated.

PMID- 20140873
TI  - [Quantitative detection of the hypermethylated RASSF1A gene in maternal plasma of
      pre-eclampsia].
AB  - OBJECTIVE: To investigate the level of hypermethylated ras association domain
      family 1A (RASSF1A) gene in maternal plasma of pre-eclampsia and its clinical
      value. METHODS: Sixty pre-eclampsia women including 30 mild and 30 severe cases
      were selected, 60 women with normal pregnancy were studied as control. Free DNA
      from plasma samples was extracted, fluorescence quantitative polymerase chain
      reaction (FQ-PCR) was used to detect the concentrations of RASSF1A gene before
      and after methylation-sensitive restriction digestion. Meanwhile, beta-actin gene
      was detected as a control to confirm complete enzyme digestion. RESULTS: The
      median concentration of hypermethylated RASSF1A gene was 3.31-fold higher in
      samples from pre-eclamptic pregnancies than that in controls. There was
      significant difference between the mild and severe pre-eclamptic subjects
      (P<0.05), with the median concentrations of 1659 copies/mL and 2036.50 copies/mL,
      respectively. CONCLUSION: Hypermethylated RASSF1A gene in pre-eclampsia plasma
      was significantly increased and the concentrations were related to the severity
      of pre-eclampsia.

PMID- 20140874
TI  - [A novel mutation of the KCNH2 gene in a family with congenital long QT
      syndrome].
AB  - OBJECTIVE: To perform mutation analysis in a family with long QT syndrome.
      METHODS: The medical record of the affected child and his parents were collected.
      The locus of gene associated with the long QT syndrome was mapped by linkage
      analysis. Mutation analysis was done by PCR-single strand conformation
      polymorphism (SSCP) and direct sequencing. RESULTS: A mutation (L539fs/47) and a
      SNP (L564L) were found in exon 7 of the KCNH2 gene of the proband. The mutation
      was from the father. CONCLUSION: A novel mutation of L539fs/47 in the KCNH2 gene
      was identified in the LQTS family, which might be the disease-causing mutation
      for the family.

PMID- 20140875
TI  - [P53 abnormality and clinical prognosis of leukemia patients with complex
      chromosomal abnormalities].
AB  - OBJECTIVE: To investigate the p53 deletion in leukemia patients with complex
      chromosomal abnormalities (CCA) and the clinical significance. METHODS: The p53
      deletion status of 38 leukemia cases with CCA and 24 cases without CCA were
      analyzed by interphase fluorescence in situ hybridization (I-FISH). RESULTS: The
      frequency of p53 deletion in the 38 patients with CCA (44.74%) was significantly
      higher than that in the 24 cases without CCA (4.16%) (P<0.01). The rate of
      complete remission in 13 cases of acute leukemia with CCA was 15.4%, with median
      survival time (MST) of 105 days. CONCLUSION: I-FISH is a rapid, accurate and
      sensitive technique for detection of p53 deletion, patients with CCA have a
      higher p53 deletion and a lower complete remission rate and MST.

PMID- 20140876
TI  - [Chromosome study on chronic lymphocytic leukemia using CpG-oligodeoxynucleotide
      as immunostimulant agent].
AB  - OBJECTIVE: To investigate whether CpG-oligodeoxynucleotide (CpG-ODN) can improve
      the detection rate of the karyotypic abnormalities in chronic lymphocytic
      leukemia (CLL). METHODS: The bone marrow (BM) or peripheral blood (PB) cells from
      57 cases of CLL were collected and cultured with CpG-ODN DSP30+interleukin-2 (IL
      2), phytohemagglutinin (PHA), pokeweed (PWM) or IL-2, respectively. Five days
      later cells were harvested for chromosome preparation. Karyotypic analysis was
      done using R banding technique. Panel fluorescence in situ hybridization (FISH)
      was carried out on 19 cases of CLL with normal karyotypes using the following
      probes: Cen12, D13S25, Rb1, ATM, p53, MYB and IgH. Genomic DNA from 21 cases of
      them was extracted from BM or PB leukocytes. The immunoglobulin variable heavy
      chain (IgVH) was amplified by polymerase chain reaction (PCR) and sequenced. CD38
      and ZAP70 expressions in the leukemic cells were determined by flow cytometry
      (FCM). RESULTS: The detection rate of karyotypic abnormalities in the CpG-ODN+IL
      2 group (43.85%) was obviously higher than that in the PHA (15.09%), PWM (17.31%)
      and IL-2 (3.13%) groups (P<0.01). Fifty-two types of karyotypic abnormalities
      were found. Among them, trisomy12 (+12) or +12 with other abnormalities were the
      most common, while translocations were the most frequent structural abnormalities
      including 3 unbalanced and 11 balanced translocations, among them 7 had
      rearrangements involving 14q32. Thirteen cases showed one or more abnormalities
      on FISH including trisomy 12 and p53 deletion each in one case, IgH rearrangement
      and partial deletion each in one case, 13q14.3 deletion in 11 cases of which 5
      cases also had Rb1 deletion, 1 case had Rb1 partial deletion. No case with ATM or
      MYB deletions was found. PCR detected IgVH mutations in 10/21 cases. FCM showed
      10/45 cases were CD38 positive, but 35 /45 were CD38 negative, 11/27 cases
      expressed ZAP70, but 16/27 did not. Among the 26 cases examined for CD38 and
      ZAP70 expressions simultaneously, 5 cases were CD38+ZAP70+, 13 were CD38-ZAP70-,
      6 were CD38-ZAP70+, and 2 were CD38+ZAP70-, respectively. Statistic analysis
      showed a correlation between complex karyotype and IgVH without mutation, but no
      association between karyotype and CD38 or ZAP70 expression was observed.
      CONCLUSION: CpG-ODN immunostimulation can obviously raise the detection rate of
      abnormal karyotypes, especially translocations in CLL. FISH is an important
      complement to conventional karyotypic analysis. The combination of both methods
      can provide more comprehensive genetic information for CLL.

PMID- 20140877
TI  - [The EXT2 gene mutation in a family with hereditary multiple exostoses].
AB  - OBJECTIVE: To identify the gene causing hereditary multiple exostoses in a
      Chinese pedigree. METHODS: Linkage analysis was carried out in the family using
      microsatellite markers close linkage to the EXT1 and EXT2 genes to define the
      candidate gene. Then the whole coding sequence and the intron-exon boundaries of
      the candidate gene were amplified and sequenced. RESULTS: The disease-causing
      gene of the family was linked to the EXT2 gene. A nonsense mutation of 536G>A in
      exon3 of the EXT2 gene was detected, which was co-segregated with the disease
      phenotype. The mutation resulted in a stop codon in codon 180. A nonpenetrant
      case was found in the family. CONCLUSION: The mutation 536G>A in the EXT2 gene is
      the disease-causing mutation in the pedigree with hereditary multiple exostoses.

PMID- 20140878
TI  - [Identification of a new human leukocyte antigen A allele, HLA-A*3020].
AB  - OBJECTIVE: To identify a novel human leukocyte antigen (HLA) A allele. METHODS: A
      new HLA-A allele was found during routine HLA genotyping by polymerase chain
      reaction-sequence specific oligonucleotide probes (PCR-SSOP) and sequencing-based
      typing (SBT). RESULTS: The novel HLA-A*30 allele was identical to A*300101 except
      that a nucleotide C at position 294 of exon 2 is substituted by A, resulting in
      codon 98 changed from GAC (D) to GAA (E). CONCLUSION: A new HLA allele, HLA
      A*3020, was identified, and was named officially by the WHO Nomenclature
      Committee.

PMID- 20140879
TI  - Social outcomes of long-term survivors of adolescent cancer.
AB  - OBJECTIVES: The study investigates psychosexual and family outcomes among German
      long-term survivors of adolescent cancer. METHODS: Survivors of cancer during
      adolescence (n = 820; age at onset of disease: M = 15.8 years, SD = 0.9, age at
      follow-up: M = 30.4, SD = 6.0 years) completed questionnaires on their family
      life and their psychosexual and autonomy development. Outcomes were compared to
      an age-matched sample (German Socio-Economic Panel, G-SOEP, n = 820, age: M =
      30.4, SD = 6.7 years) from the general population and to a control group of
      adults without cancer (n = 1027, age: M = 31.5, SD = 7.0 years). RESULTS:
      Compared to controls of the same sex, female survivors had achieved fewer
      developmental milestones in their psychosexual development such as having their
      first boyfriend, or reached these milestones later, and reported a significantly
      stronger desire for children. Male survivors were more likely to live with their
      parents when compared to same sex controls. Equivalent proportions of survivors
      and persons in the G-SOEP were living in a long-term relationship; however,
      survivors were less likely to have ever married or had children. At first
      marriage and at the birth of their first child, survivors were significantly
      older compared to the G-SOEP. About 14.5% of survivors reported cancer-related
      infertility. CONCLUSIONS: Survivors of adolescent cancer experience some social
      late effects of the disease in adulthood, such as a delayed social development as
      well as substantial differences in their family life and living conditions
      compared to healthy peers.

PMID- 20140880
TI  - An MSE-reduced estimator for the response proportion in a two-stage clinical
      trial.
AB  - Two-stage design is very useful in clinical trials for evaluating the validity of
      a specific treatment regimen. When the second stage is allowed to continue, the
      method used to estimate the response rate based on the results of both stages is
      critical for the subsequent design. The often-used sample proportion has an
      evident upward bias. However, the maximum likelihood estimator or the moment
      estimator tends to underestimate the response rate. A mean-square error weighted
      estimator is considered here; its performance is thoroughly investigated via
      Simon's optimal and minimax designs and Shuster's design. Compared with the
      sample proportion, the proposed method has a smaller bias, and compared with the
      maximum likelihood estimator, the proposed method has a smaller mean-square
      error.

PMID- 20140882
TI  - Prevention of postoperative adhesion formation by individual and combined
      administration of 4 per cent icodextrin and dimetindene maleate (Br J Surg 2009;
      96: 1476-1483).

PMID- 20140885
TI  - Long-term outcome in patients with adrenal metastases following resection of
      colorectal liver metastases (Br J Surg 2009; 96: 935-940).

PMID- 20140886
TI  - Recovery after ultrasound-guided foam sclerotherapy compared with conventional
      surgery for varicose veins (Br J Surg 2009; 96: 1262-1267).

PMID- 20140887
TI  - The role of seeing blood in non-suicidal self-injury.
AB  - Non-suicidal self-injury (NSSI) is a growing clinical problem, especially among
      adolescents and young adults. Anecdotal accounts, clinical reports, and popular
      media sources suggest that observing the blood resulting from NSSI often plays an
      important role in the behavior's reinforcement. However, research to date has not
      systematically assessed the role of blood in NSSI. The current study examined
      this phenomenon in 64 young adults from a college population with histories of
      non-suicidal skin-cutting. Approximately half the participants reported it was
      important to see blood during NSSI. These individuals reported spending five
      minutes or less looking at the blood after each instance of NSSI, and that seeing
      blood served several functions including "to relieve tension" and "makes me feel
      calm." In addition, wanting to see blood was associated with greater lifetime
      frequency of skin-cutting and greater endorsement of intrapersonal functions for
      NSSI (e.g., affect regulation, self-punishment). Finally, participants who
      reported wanting to see blood were more likely to endorse symptoms of bulimia
      nervosa and borderline personality disorder. Theoretical and clinical
      implications are discussed.

PMID- 20140888
TI  - Generation of conditional null alleles for APP and APLP2.
AB  - Proteolytical cleavage of the beta-amyloid precursor protein (APP) generates beta
      amyloid, which is deposited in the brains of patients suffering from Alzheimer's
      disease (AD). Despite the well-established key role of APP for AD pathogenesis,
      the physiological function of APP and its close homologues APLP1 and APLP2
      remains poorly understood. Previously, we generated APP(-/-) mice that proved
      viable, whereas APP(-/-)APLP2(-/-) mice and triple knockouts died shortly after
      birth, likely due to deficits of neuromuscular synaptic transmission. Here, we
      generated conditional knockout alleles for both APP and APLP2 in which the
      promoter and exon1 were flanked by loxP sites. No differences in expression were
      detectable between wt and floxed alleles, whereas null alleles were obtained upon
      crossing with Cre-transgenic deleter mice. These mice will now allow for tissue
      and time-point controlled knockout of both genes.

PMID- 20140889
TI  - A charge-sensitive loop in the FKBP38 catalytic domain modulates Bcl-2 binding.
AB  - The Bcl-2 inhibitor FKBP38 is regulated by the Ca(2+)-sensor calmodulin (CaM).
      Here we show a hitherto unknown low-affinity cation-binding site in the FKBP
      domain of FKBP38, which may afford an additional level of regulation based on
      electrostatic interactions. Fluorescence titration experiments indicate that in
      particular the physiologically relevant Ca(2+) ion binds to this site. NMR-based
      chemical shift perturbation data locate this cation-interaction site within the
      beta5-alpha1 loop (Leu90-Ile96) of the FKBP domain, which contains the acidic
      Asp92 and Asp94 side-chains. Binding constants were subsequently determined for
      K(+), Mg(2+), Ca(2+), and La(3+), indicating that the net charge and the radius
      of the ion influences the binding interaction. X-ray diffraction data furthermore
      show that the conformation of the beta5-alpha1 loop is influenced by the presence
      of a positively charged guanidinium group belonging to a neighboring FKBP38
      molecule in the crystal lattice. The position of the cation-binding site has been
      further elucidated based on pseudocontact shift data obtained by NMR via
      titration with Tb(3+). Elimination of the Ca(2+)-binding capacity by substitution
      of the respective aspartate residues in a D92N/D94N double-substituted variant
      reduces the Bcl-2 affinity of the FKBP38(35-153)/CaM complex to the same degree
      as the presence of Ca(2+) in the wild-type protein. Hence, this charge-sensitive
      site in the FKBP domain participates in the regulation of FKBP38 function by
      enabling electrostatic interactions with ligand proteins and/or salt ions such as
      Ca(2+).

PMID- 20140890
TI  - General exposures to prescription medications by race/ethnicity in a population
      based sample: results from the Boston Area Community Health Survey.
AB  - PURPOSE: Few recent U.S. studies have examined population-based patterns in
      prescription drug use and even fewer have considered detailed patterns by
      race/ethnicity. In a representative community sample, our objectives were to
      determine the most commonly used prescription drug classes, and to describe their
      use by age, gender, and race/ethnicity. METHODS: Cross-sectional epidemiologic
      study of 5503 (1767 black, 1877 Hispanic, 1859 white) community-dwelling
      participants aged 30-79 in the Boston Area Community Health (BACH) Survey (2002
      2005). Using medication information collected from an in-home interview and
      medication inventory, the prevalence of use of a therapeutic class (95%
      confidence interval (95%CI)) in the past month was estimated by gender, age
      group, and race/ethnicity. Estimates were weighted inversely to the probability
      of sampling for generalizablity to Boston, MA. RESULTS: The therapeutic class
      containing selective serotonin reuptake inhibitor/serotonin norepinephrine
      reuptake inhibitor (SSRI/SNRI) antidepressants was most commonly used (14.6%),
      followed by statins (13.9%), beta-adrenergic blockers (10.6%), and angiotensin
      converting enzyme (ACE) inhibitors (10.5%). Within all age groups and both
      genders, black participants were substantially less likely than white to use
      SSRI/SNRI antidepressants (e.g., black men: 6.0% [95%CI: 3.9-8.1%]; white men:
      15.0% [95%CI: 10.2-19.4%]). Other race/ethnic differences were observed: for
      example, black women were significantly less likely than other groups to use
      benzodiazepines (e.g., black: 2.6% [95%CI: 1.2-3.9%]; Hispanic: 9.4% [95%CI: 5.8
      13.0%]). CONCLUSIONS: Race/ethnic differences in use of prescription therapeutic
      classes were observed in our community sample. Examining therapeutic classes
      rather than individual drugs resulted in a different distribution of common
      exposures compared to other surveys.

PMID- 20140891
TI  - Dendritic cells lentivirally engineered to overexpress interleukin-10 inhibit
      contact hypersensitivity responses, despite their partial activation induced by
      transduction-associated physical stress.
AB  - BACKGROUND: Dendritic cells (DCs) constitute an attractive target for
      immunotherapeutic approaches. Because DCs are largely refractory to transfection
      with plasmid DNA, several viral transduction protocols were established. The
      potential side-effects of lentiviral transduction on the phenotype and activation
      state of DCs left unstimulated after transduction have not been assessed. There
      is a need to analyse these parameters as a result of the requirement of using DCs
      with a low activation state for therapeutic strategies intended to induce
      tolerance. METHODS: Lentivirally-transduced bone marrow (BM)-derived DCs (LV-DCs)
      in comparison with mock-transduced (Mock-DCs) and untreated DCs were analysed
      with regard to the induction of maturation processes on the RNA, protein and
      functional level. BM-DCs engineered to overexpress interleukin (IL)-10 were
      analysed for therapeutic potential in a mouse model of allergic contact
      dermatitis. RESULTS: Compared with untreated DCs, Mock-DCs and LV-DCs displayed
      an altered gene expression signature. Mock-DCs induced a stronger T cell
      proliferative response than untreated DCs. LV-DCs did not further augment the T
      cell proliferative response, but induced a slightly different T cell cytokine
      pattern compared to Mock-DCs. Accordingly, the gene promoter of the DC maturation
      marker fascin mediated efficient expression of the model transgene IL-10 in
      unstimulated-transduced BM-DCs. Nevertheless, IL-10 overexpressing BM-DCs exerted
      tolerogenic activity and efficiently inhibited the contact hypersensitivity
      response in previously hapten-sensitized mice. CONCLUSIONS: Lentiviral
      transduction of BM-DCs results in their partial activation. Nevertheless, the
      transduction of these DCs with a vector encoding the immunomodulatory cytokine IL
      10 rendered them tolerogenic. Thus, lentivirally-transduced DCs expressing
      immunomodulatory molecules represent a promising tool for induction of tolerance.

PMID- 20140892
TI  - Validation of claims-based diagnostic and procedure codes for cardiovascular and
      gastrointestinal serious adverse events in a commercially-insured population.
AB  - PURPOSE: To validate administrative claims codes with medical chart review for
      myocardial infarction (MI), ischemic stroke, and severe upper gastrointestinal
      (UGI) bleed events in a large, commercially-insured US population. METHODS: These
      validation studies were part of a larger study examining the risk of MI, ischemic
      stroke, and severe UGI bleeds in patients receiving a new prescription of
      selective cyclooxygenase (COX)-2 inhibitors (coxibs) and non-over-the-counter
      (OTC) non-steroidal anti-inflammatory drugs (NSAIDs), between 1 July 2002 and 30
      September 2004. Patients from the study cohort and other health plan members from
      the HealthCore Integrated Research Database(SM) (HIRD) experiencing these events
      were selected for these studies. The positive predictive value (PPV) of each of
      the claims code algorithms, using medical chart review as the gold standard, was
      calculated. RESULTS: Two hundred charts per event were abstracted. The PPV for MI
      was 88.4% (177/200; 95%CI, 83.2-92.5%); PPV for ischemic stroke was 87.4%
      (175/200; 95%CI, 82.0-91.7%); PPV for severe UGI bleed was 56.5% (109/193; 95%CI,
      49.2-63.6%). Refining the ischemic stroke claims algorithm resulted in a PPV of
      95.5% (95%CI, 91.0-98.2%); refining the claims algorithm for severe UGI bleed
      resulted in a PPV of 87.8% (95%CI, 78.7-94.0%). CONCLUSION: The results suggest
      that, for certain adverse events, claims data can serve as the basis for
      pharmacoepidemiology research and drug safety surveillance in the US.

PMID- 20140897
TI  - Manipulation of glycemic response with isomaltulose in a milk-based drink does
      not affect cognitive performance in healthy adults.
AB  - Previous research suggests that glucoregulation and nutrient interventions, which
      alter circulating glucose, impact cognitive function. To examine the effect of
      modulating glycemic response using isomaltulose on cognitive function 24 healthy
      male adult participants consumed energy and macronutrient-matched milk-based
      drinks containing 50 g isomaltulose, 50 g sucrose or a water control in a
      counterbalanced within-subject design. Interstitial glucose was measured
      continuously in 12 subjects and all provided 9 capillary measures on each test
      day. A 30-min cognitive test battery was administered before and twice (+35 and
      +115 min) after drink ingestion. Immediate, delayed, recognition, verbal and
      working memory, and psychomotor performance were assessed. Glycemic profiles
      induced by the drinks differed significantly during the first but not the second
      post-drink test battery. Neither administration of the sucrose nor isomaltulose
      drinks produced consistent effects on verbal or working memory, or psychomotor
      performance. This study used isomaltulose as an investigative tool to lower
      glycemic response. Importantly, it demonstrates a lack of effect of modulating
      glucose on cognitive performance based on reliable, continuously measured
      glycemia. It refutes the hypothesis that glycemia is associated with cognitive
      performance and questions the suggestion that isomaltulose has an effect on
      cognitive performance.

PMID- 20140898
TI  - Identification of aminoreductones as active components in Maillard reaction
      mixtures inducing nuclear NF-kappaB translocation in macrophages.
AB  - Coffee, a highly processed food, and Maillard mixtures are able to activate
      nuclear factor kappaB translocation in macrophages via generation of hydrogen
      peroxide. In this study, a substructure library was prepared and used to identify
      Maillard products that are responsible for this effect. Three different Maillard
      reaction products with aminoreductone substructure (C(6)-aminoreductone, C(4)
      aminoreductone, and aminohexose reductone) strongly induce nuclear factor kappaB
      translocation in macrophages. The effect was almost completely blocked by co
      incubation with catalase, indicating that cellular activation was mediated by the
      ability of the test compounds to generate hydrogen peroxide. The cellular effect
      of a Maillard mixture, which was produced under conditions favoring
      aminoreductone formation, could be almost completely related to the presence of
      C(6)-aminoreductone.

PMID- 20140899
TI  - Biological effects on granulosa cells of hydroxylated and methylated resveratrol
      analogues.
AB  - Several resveratrol analogues have been designed to improve bioactivity: among
      these polymethoxystilbenes appear to be particularly promising. The present study
      was set up to investigate the biological functions of polymethoxystilbenes 2 and
      3, recently found in our lab as antiangiogenic agents, on a well-defined swine
      granulosa cell model. Proliferative activity and effects on steroidogenesis were
      evaluated, as well as the effect on granulosa cell vascular endothelial growth
      factor (VEGF) production, since these cells in basic conditions synthesize the
      main proangiogenic peptide. Moreover, we considered the effect of these two
      resveratrol analogues on granulosa cell redox status. Analogue 3 inhibited
      granulosa cell growth, while it stimulated steroidogenesis. A similar effect was
      displayed by 2 on estradiol 17beta production and cell proliferation at the
      highest concentration tested. On the other hand, at the same dosage 2 decreased
      progesterone levels. Both analogues inhibited VEGF output. Granulosa cell redox
      status was unaffected by resveratrol analogue 2 while the highest concentration
      of 3 stimulated free radicals generation and scavenging enzyme activities. The
      overall results indicate that analogue 3 is the more powerful compound, thus
      suggesting that a slight modification in the structure markedly increases
      effectiveness. These data could be useful to develop more active resveratrol
      analogues for therapeutic use.

PMID- 20140900
TI  - Hans van Houwelingen and the art of summing up.
AB  - Some personal remarks about Hans van Houwelingen's approach to biostatistics in
      general are followed by a discussion of his article with Koos Zwinderman and Theo
      Stijnen outlining a bivariate approach to meta-analysis. It is concluded that
      this is more radical than many may realise in that it permits inter-trial
      information to be recovered. This has some advantages but in theory opens the
      door to bias. It is concluded that in practice the size of this bias is likely to
      be small. I end with some further personal remarks to Hans.

PMID- 20140901
TI  - A note on variance estimation of the Aalen-Johansen estimator of the cumulative
      incidence function in competing risks, with a view towards left-truncated data.
AB  - The Aalen-Johansen estimator is the standard nonparametric estimator of the
      cumulative incidence function in competing risks. Estimating its variance in
      small samples has attracted some interest recently, together with a critique of
      the usual martingale-based estimators. We show that the preferred estimator
      equals a Greenwood-type estimator that has been derived as a recursion formula
      using counting processes and martingales in a more general multistate framework.
      We also extend previous simulation studies on estimating the variance of the
      Aalen-Johansen estimator in small samples to left-truncated observation schemes,
      which may conveniently be handled within the counting processes framework. This
      investigation is motivated by a real data example on spontaneous abortion in
      pregnancies exposed to coumarin derivatives, where both competing risks and left
      truncation have recently been shown to be crucial methodological issues (Meister
      and Schaefer (2008), Reproductive Toxicology 26, 31-35). Multistate-type software
      and data are available online to perform the analyses. The Greenwood-type
      estimator is recommended for use in practice.

PMID- 20140902
TI  - The antimicrobial peptide LL-37 modulates the inflammatory and host defense
      response of human neutrophils.
AB  - The human cathelicidin antimicrobial peptide acts as an effector molecule of the
      innate immune system with direct antimicrobial and immunomodulatory effects. The
      aim of this study was to test whether the cathelicidin LL-37 modulates the
      response of neutrophils to microbial stimulation. Human neutrophils were exposed
      to LPS, Staphylococcus aureus and Pseudomonas aeruginosa subsequent to incubation
      with LL-37 and cytokine release was measured by ELISA. The incubation with LL-37
      significantly decreased the release of proinflammatory cytokines from stimulated
      human neutrophils. ROS production of neutrophils was determined by a luminometric
      and a flow cytometry method. The peptide induced the production of ROS and the
      engulfment of bacteria into neutrophils. Peritoneal mouse neutrophils isolated
      from CRAMP-deficient and WT animals were treated with LPS and TNF-alpha in the
      supernatant was measured by ELISA. Antimicrobial activity of neutrophils was
      detected by incubating neutrophils isolated from CRAMP-knockout and WT mice with
      bacteria. Neutrophils from CRAMP-deficient mice released significantly more TNF
      alpha after bacterial stimulation and showed decreased antimicrobial activity as
      compared to cells from WT animals. In conclusion, LL-37 modulates the response of
      neutrophils to bacterial activation. Cathelicidin controls the release of
      inflammatory mediators while increasing antimicrobial activity of neutrophils.

PMID- 20140903
TI  - Continuous CD27 triggering in vivo strongly reduces NK cell numbers.
AB  - NK cells are important mediators of the early defense. In mice, immature and
      mature NK (mNK) cells constitutively express the TNF receptor family member CD27;
      however, mNK cells eventually lose CD27 expression and become resting NK cells.
      Interaction of CD27 with its ligand, CD70, enhances proliferation and effector
      functions of NK cells. We used mice that constitutively express CD70 on B cells
      (CD70-Tg) to study the in vivo effects of continuous triggering of CD27 on NK
      cells. Continuous CD70-CD27 interaction resulted in strongly down-modulated CD27
      expression on NK cells and gradually reduced absolute NK cell numbers. This
      reduction was most prominent in the mNK cell subpopulation and was at least
      partially due to increased apoptosis. Residual NK cells showed lower expression
      of activating Ly49 receptors and normal (liver) or decreased (spleen) IFN-gamma
      production. Nevertheless, NK cells from CD70-Tg mice displayed higher YAC-1
      killing capacities. CD70-Tg NK cells exhibited up-regulated expression of NKG2D,
      which is in accordance with the increased YAC-1 lysis, as this is mainly NKG2D
      dependent. Taken together, this study is the first to demonstrate that continuous
      CD70 triggering of CD27 on NK cells in vivo results in a severe reduction of NK
      cells. On a single cell basis, however, residual NK cells display enhanced
      cytotoxicity.

PMID- 20140905
TI  - XTandem Parser: an open-source library to parse and analyse X!Tandem MS/MS search
      results.
AB  - Identification of proteins by MS plays an important role in proteomics. A crucial
      step concerns the identification of peptides from MS/MS spectra. The X!Tandem
      Project (http://www.thegpm.org/tandem) supplies an open-source search engine for
      this purpose. In this study, we present an open-source Java library called
      XTandem Parser that parses X!Tandem XML result files into an easily accessible
      and fully functional object model (http://xtandem-parser.googlecode.com). In
      addition, a graphical user interface is provided that functions as a usage
      example and an end-user visualization tool.

PMID- 20140904
TI  - Complement C5a regulates IL-17 by affecting the crosstalk between DC and
      gammadelta T cells in CLP-induced sepsis.
AB  - Complement 5a (C5a) and Interleukin-17 (IL-17) are two important inflammatory
      mediators in sepsis. Here we studied the mechanisms underlying regulation of IL
      17 by anaphylatoxin C5a. We found that C5a blockade increased the survival rate
      of mice following cecal ligation and puncture (CLP)-induced sepsis and decreased
      IL-17 expression in vivo. IL-17 was secreted mainly by gammadelta T cells in this
      model. Importantly, our data suggest that C5a participates in the regulation of
      IL-17 secretion by gammadelta T cells. Dendritic cells (DC) were found to act as
      a "bridge" between C5a and gammadelta T cells in a mechanism involving IL-6 and
      transforming growth factor beta (TGF-beta). These results imply that C5a affects
      the crosstalk between DC and gammadelta T cells during sepsis development, and
      this may result in a large production of inflammatory mediators such as IL-17.

PMID- 20140906
TI  - A comparative proteomic analysis of HepG2 cells incubated by S(-) and R(+)
      enantiomers of anti-coagulating drug warfarin.
AB  - Warfarin is a commonly prescribed oral anti-coagulant with narrow therapeutic
      index. It interferes with vitamin K cycle to achieve anti-coagulating effects.
      Warfarin has two enantiomers, S(-) and R(+) and undergoes stereoselective
      metabolism, with the S(-) enantiomer being more effective. We reported that the
      intracellular protein profile in HepG2 cells incubated with S(-) and R(+)
      warfarin, using iTRAQ-coupled 2-D LC-MS/MS. In samples incubated with S(-) and
      R(+) warfarin alone, the multi-task protein Protein SET showed significant
      elevation in cells incubated with S(-) warfarin but not in those incubated with
      R(+) warfarin. In cells incubated with individual enantiomers of warfarin in the
      presence of vitamin K, protein disulfide isomerase A3 which is known as a glucose
      regulated protein, in cells incubated with S(-) warfarin was found to be down
      regulated compared to those incubated with R(+) warfarin. In addition, Protein DJ
      1 and 14-3-3 Proteinsigma were down-regulated in cells incubated with either S(-)
      or R(+) warfarin regardless of the presence of vitamin K. Our results indicated
      that Protein DJ-1 may act as an enzyme for expression of essential enzymes in
      vitamin K cycle. Taken together, our findings provided molecular evidence on a
      comprehensive protein profile on warfarin-cell interaction, which may shed new
      lights on future improvement of warfarin therapy.

PMID- 20140907
TI  - Virtual expert mass spectrometrist: iTRAQ tool for database-dependent search,
      quantitation and result storage.
AB  - A frequent goal of MS-based proteomics experiments nowadays is to quantify
      changes in the abundance of proteins across several biological samples. The iTRAQ
      labeling method is a powerful technique; when combined with LC coupled to MS/MS
      it allows relative quantitation of up to eight different samples simultaneously.
      Despite the usefulness of iTRAQ current software solutions have limited
      functionality and require the combined use of several software programs for
      analysis of the data from different MS vendors. We developed an integrated tool,
      now available in the virtual expert mass spectrometrist (VEMS) program, for
      database-dependent search of MS/MS spectra, quantitation and database storage for
      iTRAQ-labeled samples. VEMS also provides useful alternative report types for
      large-scale quantitative experiments. The implemented statistical algorithms
      build on quantitative algorithms previously used in proposed iTRAQ tools as
      described in detail herein. We propose a new algorithm, which provides more
      accurate peptide ratios for data that show an intensity-dependent saturation. The
      accuracy of the proposed iTRAQ algorithm and the performance of VEMS are
      demonstrated by comparing results from VEMS, MASCOT and PEAKS Q obtained by
      analyzing data from a reference mixture of six proteins. Users can download VEMS
      and test data from "http://www.portugene.com/software.html".

PMID- 20140908
TI  - Synthesis of poly(vinyl alcohol)/C(60) and poly(N-vinylpyrrolidone)/C(60)
      nanohybrids as potential photodynamic cancer therapy agents.
AB  - Well-defined poly(vinyl acetate) (PVAc) and poly(N-vinylpyrrolidone)-co
      poly(vinyl acetate) (PNVP-co-PVAc) chains end-capped by Co(acac)(2)
      (acac=acetylacetonate) and prepared by cobalt-mediated radical polymerization
      (CMRP) are grafted onto a fullerene. Homolytic Co-C bond cleavage of the polymer
      chain ends at 30 degrees C releases the polymeric radicals that add onto C(60),
      thereby leading to the corresponding PVAc/C(60) and PNVP-co-PVAc/C(60)
      nanohybrids. The [polymer-Co(acac)(2)]/[C(60)] molar ratio was varied to adjust
      the structure of the nanohybrids, and more particularly the number of grafted
      arms. Finally, the potential of the hydrosoluble PVOH/C(60) nanohybrids, which
      result from the methanolysis of the ester groups of PVAc/C(60), and of the PNVP
      co-PVAc/C(60) nanohybrids as photosensitizers for photodynamic therapy (PDT), was
      approached. First, photobleaching tests demonstrated the ability of these
      nanohybrids to produce singlet oxygen upon irradiation, which can play a role in
      cell damage. Second, cell viability assays demonstrated that both types of
      nanohybrids are deprived of intrinsic cytotoxicity in the dark, whereas they
      promoted significant cell mortality when subjected to light treatment. The
      selective response of these materials to irradiation makes them promising
      compounds for PDT.

PMID- 20140909
TI  - Neuro-mesodermal patterns in artificially deformed embryonic explants: a role for
      mechano-geometry in tissue differentiation.
AB  - The mutual arrangement of neural and mesodermal rudiments in artificially bent
      double explants of Xenopus laevis suprablastoporal areas was compared with that
      of intact explants. While some of the bent explants straightened or became
      spherical, most retained and actively reinforced the imposed curvature, creating
      folds on their concave sides and expanding convex surfaces. In the intact
      explants, the arrangement of neural and mesodermal rudiments exhibited a distinct
      antero-posterior polarity, with some variability. In the bent explants, this
      polarity was lost: the neural rudiments were shifted towards concave while the
      mesodermal tissues moved towards the convex side, embracing the neural rudiments
      in a horseshoe-shaped manner. We associate these drastic changes in neuro
      mesodermal patterning with the active extension and contraction of the convex and
      concave sides, respectively, triggered by the imposed deformations. We speculate
      that similar events are responsible for the establishment of neuro-mesodermal
      patterns during normal development.

PMID- 20140910
TI  - Canonical wingless signaling regulates cone cell specification in the Drosophila
      retina.
AB  - Correct tissue patterning during development involves multiple morphogenetic
      events that include specification of different cell fates, cell proliferation,
      cell death, and coordinated changes in cell shape, position, and adhesion. Here,
      we use the Drosophila retina to explore the molecular mechanisms that regulate
      and integrate these various events. In a previous report, we found that wingless
      (wg) was required to induce a previously unknown surge of cell death ("early
      death") in the pupal retina. Here, we show that wg is also required to induce the
      more widely studied mid-pupal cell death ("late death") in a process that
      involves regulation of DIAP1. Furthermore, our data suggest that wg has a
      previously unreported role in specifying the glial-like cone cells. This activity
      requires canonical Wg signaling and is linked with Notch pathway activity. Our
      work broadens the role of canonical Wg signaling to encompass multiple patterning
      steps in the emerging Drosophila retina.

PMID- 20140912
TI  - Understanding the role of asymmetric cell division in cancer using C. elegans.
AB  - Asymmetric cell division is an important process to generate cell diversity and
      maintain tissue homeostasis. Recent evidence suggests that this process may also
      be crucial to prevent tumor formation. In the past 30 years, the embryo of the
      nematode Caenorhabditis elegans has proven to be a very powerful model to study
      the molecular and cellular basis of asymmetric cell division. Understanding this
      process in Caenorhabditis elegans may thus lead to a better understanding of stem
      cell function and tumorigenesis in humans.

PMID- 20140911
TI  - Integration of diverse inputs in the regulation of Caenorhabditis elegans DAF
      16/FOXO.
AB  - In a remarkably conserved insulin signaling pathway that is well-known for its
      regulation of longevity in worms, flies, and mammals, the major C. elegans
      effector of this pathway, DAF-16/FOXO, also modulates many other physiological
      processes. This raises the question of how DAF-16/FOXO chooses the correct
      targets to achieve the appropriate response in a particular context. Here, we
      review current knowledge of tissue-specificity and interacting partners that
      modulate DAF-16/FOXO functional output.

PMID- 20140913
TI  - A definitive answer to a bonding quandary? The role of one-electron resonance
      structures in the bonding of a {Cu3S2}3+ core.

PMID- 20140914
TI  - UC Pd: a new form of Pd/C for Sonogashira couplings.
AB  - Screening of different sources of Pd/C shows reagents of highly variable
      nanoparticle sizes and oxidation states of the metal. Typically, catalysts with
      higher surface area are viewed as likely to be the more reactive. In this paper a
      new form of Pd/C, "UC Pd" is described that is shown to contain larger
      nanoparticles yet it is the most reactive catalyst of those sold commercially for
      Sonogashira coupling reactions. UC Pd functions efficiently in the absence of a
      copper co-catalyst, under very mild and "green" conditions using inexpensive 95%
      EtOH at 50 degrees C. It is also the only form of Pd/C that can be recycled. In
      side-by-side reactions with several commercially available forms of Pd/C, none
      compete successfully with UC Pd under standardized conditions. Physical data
      obtained from extensive surface analysis using TEM, XRD, XPS, and CO-TPD
      measurements lead to an explanation behind the unique reactivity of this new
      recyclable form of Pd/C.

PMID- 20140915
TI  - Biaryl phosphite-oxazoline ligands from the chiral pool: highly efficient modular
      ligands for the asymmetric Pd-catalyzed Heck reaction.
AB  - A highly modular library of readily available phosphite-oxazoline ligands L1-L21a
      g was successfully applied in the asymmetric Pd-catalyzed Heck reactions of
      several substrates and triflates under thermal and microwave conditions. This
      ligand library contains three main ligand structures that have been designed by
      systematic modification of one of the most successful ligand families developed
      for this process. As well as studying the effect of these three ligand structures
      on the catalytic performance, we also evaluated the effect of modifying several
      ligand parameters in these ligand structures. The effectiveness of these ligands
      at transferring the chiral information into the product can be tuned by correctly
      choosing the ligand components. Both enantiomers of the Heck coupling products
      were obtained in excellent activities (conversion: >100% in 10 min),
      regioselectivities (>99%) and enantioselectivities (>99% ee). Under microwave
      irradiation conditions, the reaction times were considerably shorter (full
      conversion was achieved in a few minutes) and the regio- and enantioselectivities
      were still excellent.

PMID- 20140916
TI  - A 93Nb solid-state NMR and density functional theory study of four- and six
      coordinate niobate systems.
AB  - A variable B(0) field static (broadline) NMR study of a large suite of niobate
      materials has enabled the elucidation of high-precision measurement of (93)Nb NMR
      interaction parameters such as the isotropic chemical shift (delta(iso)),
      quadrupole coupling constant and asymmetry parameter (C(Q) and eta(Q)), chemical
      shift span/anisotropy and skew/asymmetry (Omega/Deltadelta and kappa/eta(delta))
      and Euler angles (alpha, beta, gamma) describing the relative orientation of the
      quadrupolar and chemical shift tensorial frames. These measurements have been
      augmented with ab initio DFT calculations by using WIEN2k and NMR-CASTEP codes,
      which corroborate these reported values. Unlike previous assertions made about
      the inability to detect CSA (chemical shift anisotropy) contributions from Nb(V)
      in most oxo environments, this study emphasises that a thorough variable B(0)
      approach coupled with the VOCS (variable offset cumulative spectroscopy)
      technique for the acquisition of undistorted broad (-1/2<-->+1/2) central
      transition resonances facilitates the unambiguous observation of both quadrupolar
      and CSA contributions within these (93)Nb broadline data. These measurements
      reveal that the (93)Nb electric field gradient tensor is a particularly sensitive
      measure of the immediate and extended environments of the Nb(V) positions, with
      C(Q) values in the 0 to >80 MHz range being measured; similarly, the delta(iso)
      (covering an approximately 250 ppm range) and Omega values (covering a 0 to
      approximately 800 ppm range) characteristic of these niobate systems are also
      sensitive to structural disposition. However, their systematic rationalisation in
      terms of the Nb-O bond angles and distances defining the immediate Nb(V) oxo
      environment is complicated by longer-range influences that usually involve other
      heavy elements comprising the structure. It has also been established in this
      study that the best computational method(s) of analysis for the (93)Nb NMR
      interaction parameters generated here are the all-electron WIEN2k and the gauge
      included projector augmented wave (GIPAW) NMR-CASTEP DFT approaches, which
      account for the short- and long-range symmetries, periodicities and interaction
      potential characteristics for all elements (and particularly the heavy elements)
      in comparison with Gaussian 03 methods, which focus on terminated portions of the
      total structure.

PMID- 20140917
TI  - One-dimensional ferromagnetically coupled bimetallic chains constructed with
      trans-[Ru(acac)2(CN)2]-: syntheses, structures, magnetic properties, and density
      functional theoretical study.
AB  - Four cyano-bridged 1D bimetallic polymers have been prepared by using the
      paramagnetic building block trans-[Ru(acac)(2)(CN)(2)](-) (Hacac=acetylacetone):
      {[{Ni(tren)}{Ru(acac)(2)(CN)(2)}][ClO(4)].CH(3)OH}(n) (1) (tren=tris(2
      aminoethyl)amine), {[{Ni(cyclen)}{Ru(acac)(2)(CN)(2)}][ClO(4)].CH(3)OH}(n) (2)
      (cyclen=1,4,7,10-tetraazacyclododecane), {[{Fe(salen)}{Ru(acac)(2)(CN)(2)}]}(n)
      (3) (salen(2-)=N,N'-bis(salicylidene)-o-ethyldiamine dianion) and [{Mn(5,5'
      Me(2)salen)}(2){Ru(acac)(2)(CN)(2)}][Ru(acac)(2)(CN)(2)].2CH(3)OH (4) (5,5'
      Me(2)salen=N,N'-bis(5,5'-dimethylsalicylidene)-o-ethylenediimine). Compounds 1
      and 2 are 1D, zigzagged NiRu chains that exhibit ferromagnetic coupling between
      Ni(II) and Ru(III) ions through cyano bridges with J=+1.92 cm(-1), zJ'=-1.37 cm(
      1), g=2.20 for 1 and J=+0.85 cm(-1), zJ'=-0.16 cm(-1), g=2.24 for 2. Compound 3
      has a 1D linear chain structure that exhibits intrachain ferromagnetic coupling
      (J=+0.62 cm(-1), zJ'=-0.09 cm(-1), g=2.08), but antiferromagnetic coupling occurs
      between FeRu chains, leading to metamagnetic behavior with T(N)=2.6 K. In
      compound 4, two Mn(III) ions are coordinated to trans-[Ru(acac)(2)(CN)(2)](-) to
      form trinuclear Mn(2)Ru units, which are linked together by pi-pi stacking and
      weak Mn...O* interactions to form a 1D chain. Compound 4 shows slow magnetic
      relaxation below 3.0 K with phi=0.25, characteristic of superparamagnetic
      behavior. The Mn(III)...Ru(III) coupling constant (through cyano bridges) and the
      Mn(III)...Mn(III) coupling constant (between the trimers) are +0.87 and +0.24 cm(
      1), respectively. Compound 4 is a novel single-chain magnet built from Mn(2)Ru
      trimers through noncovalent interactions. Density functional theory (DFT)
      combined with the broken symmetry state method was used to calculate the
      molecular magnetic orbitals and the magnetic exchange interactions between
      Ru(III) and M (M=Ni(II), Fe(III), and Mn(III)) ions. To explain the somewhat
      unexpected ferromagnetic coupling between low-spin Ru(III) and high-spin Fe(III)
      and Mn(III) ions in compounds 3 and 4, respectively, it is proposed that apart
      from the relative symmetries, the relative energies of the magnetic orbitals may
      also be important in determining the overall magnetic coupling in these
      bimetallic assemblies.

PMID- 20140918
TI  - A light-controlled molecular brake with complete ON-OFF rotation.
AB  - A light-controlled molecular machine based on cyclic azobenzenophanes consisting
      of a dioxynaphthalene rotating unit and a photoisomerizable dioxyazobenzene unit
      bridged by methylene spacers is reported. In compounds 1 and 2, 1,5- and 2,6
      dioxynaphthalene moieties, respectively, are linked to p-dioxyazobenzene by
      different methylene spacers (n=2 in 1a and 2; n=3 in 1b), whereas a 1,5
      dioxynaphthalene moiety is bonded to m-dioxyazobenzene by bismethylene spacers in
      3. In 1b and 2, the naphthalene ring can rotate freely in both the trans and cis
      states at room temperature. The rotation speed can be controlled either by
      photoinduced reversible trans-cis (E-Z) isomerization of the azobenzene or by
      keeping the system at low temperature, as is evident from its NMR spectra.
      Furthermore, for the first time, we demonstrate a light-controlled molecular
      brake, wherein the rotation of the naphthalene moiety through the cyclophane is
      completely OFF in the trans isomer of compound 3 due to its smaller cavity size.
      Such restricted rotation imparts planar chirality to the molecule, and the
      corresponding enantiomers could be resolved by chiral HPLC. However, the rotation
      of the naphthalene moiety is rendered ON in the cis isomer due to its increased
      cavity size, and it is manifested experimentally by the racemization of the
      separated enantiomers by photoinduced E-Z isomerization.

PMID- 20140919
TI  - Facile chemical solution deposition of high-mobility epitaxial germanium films on
      silicon.

PMID- 20140920
TI  - The first general, efficient and highly enantioselective reduction of
      quinoxalines and quinoxalinones.

PMID- 20140921
TI  - Antiferromagnetism or delocalized spin in a Cu3S2 core?

PMID- 20140922
TI  - Studying the origin of the antiferromagnetic to spin-canting transition in the
      beta-p-NCC6F4CNSSN* molecular magnet.
AB  - The crystal structure of the spin-canted antiferromagnet beta-p-NCC(6)F(4)CNSSN*
      at 12 K (reported in this work) was found to adopt the same orthorhombic space
      group as that previously determined at 160 K. The change in the magnetic
      properties of these two crystal structures has been rigorously studied by
      applying a first-principles bottom-up procedure above and below the magnetic
      transition temperature (36 K). Calculations of the magnetic exchange pathways on
      the 160 K structure reveal only one significant exchange coupling (J(d1)=-33.8
      cm(-1)), which generates a three-dimensional diamond-like magnetic topology
      within the crystal. The computed magnetic susceptibility, chi(T), which was
      determined by using this magnetic topology, quantitatively reproduces the
      experimental features observed above 36 K. Owing to the anisotropic contraction
      of the crystal lattice, both the geometry of the intermolecular contacts at 12 K
      and the microscopic J(AB) radical-radical magnetic interactions change: the J(d1)
      radical-radical interaction becomes even more antiferromagnetic (-43.2 cm(-1))
      and two additional ferromagnetic interactions appear (+7.6 and +7.3 cm(-1)).
      Consequently, the magnetic topologies of the 12 and 160 K structures differ: the
      12 K magnetic topology exhibits two ferromagnetic sublattices that are
      antiferromagnetically coupled. The chi(T) curve, computed below 36 K at the limit
      of zero magnetic field by using the 12 K magnetic topology, reproduces the shape
      of the residual magnetic susceptibility (having subtracted the contribution to
      the magnetization arising from spin canting). The evolution of these two
      ferromagnetic J(AB) contributions explains the change in the slope of the
      residual magnetic susceptibility in the low-temperature region.

PMID- 20140923
TI  - A cobalt-catalyzed sulfonate/copper exchange for the preparation of highly
      functionalized electron-deficient aryl copper reagents.

PMID- 20140924
TI  - The native conformation of the human VDAC1 N terminus.

PMID- 20140925
TI  - Water splitting by visible light: a nanophotocathode for hydrogen production.

PMID- 20140926
TI  - A persistent dipotassium 1,2,4-diazaphospholide radical complex: synthesis, X-ray
      structure, and bonding.

PMID- 20140927
TI  - Spin divergence induced by exohedral modification: ESR study of Sc3C2@C80
      fulleropyrrolidine.

PMID- 20140928
TI  - Nanotubular paramagnetic probes as contrast agents for magnetic resonance imaging
      based on the diffusion tensor.

PMID- 20140929
TI  - Multiferroic materials: the attractive approach of metal-organic frameworks
      (MOFs).

PMID- 20140930
TI  - A biomimetic ferric hydroperoxo porphyrin intermediate.

PMID- 20140931
TI  - A giant silver alkynyl cage with sixty silver(I) ions clustered around
      polyoxometalate templates.

PMID- 20140932
TI  - Ruthenium-catalyzed alkene synthesis by the decarbonylative coupling of aldehydes
      with alkynes.

PMID- 20140936
TI  - Current rectification in temperature-responsive single nanopores.
AB  - Herein we demonstrate a fully abiotic smart single-nanopore device that rectifies
      ionic current in response to the temperature. The temperature-responsive nanopore
      ionic rectifier can be switched between a rectifying state below 34 degrees C and
      a non-rectifying state above 38 degrees C actuated by the phase transition of the
      poly(N-isopropylacrylamide) [PNIPAM] brushes. On the rectifying state, the
      rectifying efficiency can be enhanced by the dehydration of the attached PNIPAM
      brushes below the LCST. When the PNIPAM brushes have sufficiently collapsed, the
      nanopore switches to the non-rectifying state. The concept of the temperature
      responsive current rectification in chemically-modified nanopores paves a new way
      for controlling the preferential direction of the ion transport in nanofluidics
      by modulating the temperature, which has the potential to build novel
      nanomachines with smart fluidic communication functions for future lab-on-chip
      devices.

PMID- 20140934
TI  - Cloning and characterization of the ravidomycin and chrysomycin biosynthetic gene
      clusters.
AB  - The gene clusters responsible for the biosynthesis of two antitumor antibiotics,
      ravidomycin and chrysomycin, have been cloned from Streptomyces ravidus and
      Streptomyces albaduncus, respectively. Sequencing of the 33.28 kb DNA region of
      the cosmid cosRav32 and the 34.65 kb DNA region of cosChry1-1 and cosChryF2
      revealed 36 and 35 open reading frames (ORFs), respectively, harboring tandem
      sets of type II polyketide synthase (PKS) genes, D-ravidosamine and D-virenose
      biosynthetic genes, post-PKS tailoring genes, regulatory genes, and genes of
      unknown function. The isolated ravidomycin gene cluster was confirmed to be
      involved in ravidomycin biosynthesis through the production of a new analogue of
      ravidomycin along with anticipated pathway intermediates and biosynthetic shunt
      products upon heterologous expression of the cosmid, cosRav32, in Streptomyces
      lividans TK24. The identity of the cluster was further verified through cross
      complementation of gilvocarcin V (GV) mutants. Similarly, the chrysomycin gene
      cluster was demonstrated to be indirectly involved in chrysomycin biosynthesis
      through cross-complementation of gilvocarcin mutants deficient in the oxygenases
      GilOII, GilOIII, and GilOIV with the respective chrysomycin monooxygenase
      homologues. The ravidomycin glycosyltransferase (RavGT) appears to be able to
      transfer both amino- and neutral sugars, exemplified through the structurally
      distinct 6-membered D-ravidosamine and 5-membered D-fucofuranose, to the coumarin
      based polyketide derived backbone. These results expand the library of
      biosynthetic genes involved in the biosyntheses of gilvocarcin class compounds
      that can be used to generate novel analogues through combinatorial biosynthesis.

PMID- 20140937
TI  - Taking quinazoline as a general support-Nog to design potent and selective kinase
      inhibitors: application to FMS-like tyrosine kinase 3.

PMID- 20140938
TI  - Failure of xenoimplantation using porcine synovium-derived stem cell-based
      cartilage tissue constructs for the repair of rabbit osteochondral defects.
AB  - The use of xenogeneic tissues offers many advantages with respect to
      availability, quality control, and timing of tissue harvest. Our previous study
      indicated that implantation of premature tissue constructs from allogeneic
      synovium-derived stem cells (SDSCs) facilitated cartilage tissue regeneration.
      The present study investigated the feasibility of xenoimplantation of SDSC-based
      premature tissue constructs for the repair of osteochondral defects. Porcine
      SDSCs were mixed with fibrin gel, seeded in polyglycolic acid (PGA) scaffolds,
      and cultured in a rotating bioreactor system supplemented for 1 month with growth
      factor cocktails. The engineered porcine premature tissues were implanted to
      repair surgically induced osteochondral defects in the medial femoral condyles of
      12 rabbits. Three weeks after surgery, the xenoimplantation group exhibited a
      smooth, whitish surface while the untreated control remained empty. Surprisingly,
      6 months after surgery, the xenoimplantation group displayed some tissue loss
      while the untreated control group was overgrown with fibrocartilage tissue. In
      the xenoimplantation group, chronic inflammation was observed in synovial tissue
      where porcine major histocompatibility complex (MHC) class II antigen positively
      stained in the engulfed foreign bodies. In addition, porcine source cells also
      migrated from the implantation site and may have been responsible for the
      observed loss of glycosaminoglycans (GAGs) underneath surrounding articular
      cartilage. The histological score was much worse in the xenoimplanted group than
      in the untreated control. Our study suggested that SDSC-based xenogeneic tissue
      constructs might cause delayed immune rejection. Xenotransplantation may not be
      an appropriate approach to repair osteochondral defects.

PMID- 20140939
TI  - Methylthioadenosine phosphorylase and activated insulin-like growth factor-1
      receptor/insulin receptor: potential therapeutic targets in chordoma.
AB  - Currently there is no effective chemotherapy for chordoma. Recent studies report
      co-expression of insulin-like growth factor-1 receptor (IGF1R) and its cognate
      ligand in chordoma, but it is unknown whether this receptor tyrosine kinase is
      activated in these tumours. Additionally, genetic studies have confirmed frequent
      deletions of chromosome 9p in chordomas, which encompasses the cyclin-dependent
      kinase inhibitor 2A (CDKN2A) locus. Another gene in this region,
      methylthioadenosine phosphorylase (MTAP), is an essential enzyme of the purine
      salvage pathway and has therapeutic relevance because MTAP-deficient cells are
      particularly sensitive to inhibitors of de novo purine synthesis. We investigated
      whether these pathways might be potential therapeutic targets for chordoma.
      Paraffin-embedded tissue samples from 30 chordomas were analysed by
      immunohistochemistry for expression of the phosphorylated isoforms of IGF1R or
      the insulin receptor (pIGF1R/pIR) and selected downstream signalling molecules,
      including BCL2-associated agonist of cell death protein (BAD). Expression of
      CDKN2A and MTAP proteins was also assessed. Skeletal chondrosarcomas, benign
      notochordal cell tumours, and fetal notochord were studied for comparison.
      Phosphorylated IGF1R/IR was detected in 41% of chordomas, together with activated
      downstream signalling molecules, and pIGF1R/pIR was absent in benign notochordal
      cell tumours and fetal notochord. Thirty-nine per cent of chordomas were negative
      for MTAP immunoreactivity. Patients with pIGF1R/pIR-positive tumours showed
      significantly decreased median disease-free survival in multivariate survival
      analysis (p = 0.036), whereas phosphorylation of BAD at serine-99 was found to be
      associated with a favourable prognosis (p = 0.002). Approximately 40% of
      chordomas demonstrate evidence of activation of the IGF1R/IR signalling pathway
      or loss of a key enzyme in the purine salvage pathway. Aberrant signalling
      cascades and disrupted metabolic pathways such as these may represent
      opportunities for novel targeted therapeutic approaches for the treatment of
      chordoma.

PMID- 20140940
TI  - Distinguishing affective and somatic dimensions of pain and depression: a
      confirmatory factor analytic study.
AB  - In this study, we examined the overlap between pain and depression in a sample of
      342 chronic pain patients treated at a specialty pain clinic. Confirmatory factor
      analysis was conducted to test the differentiation of pain and depression
      measured as latent factors derived from the subscales of the Short Form McGill
      Pain Questionnaire and the Center for Epidemiological Studies Depression Scale.
      The affective pain subscale did not load on latent depression and the somatic
      depression subscale loaded weakly on latent pain. Although pain and depression
      are linked, we found that affective pain is distinct from depression, and that
      somatic depression is distinct from pain. This finding justifies further
      examination of the casual relationship between pain and depression.

PMID- 20140943
TI  - Randomized controlled trial and cost-effectiveness analysis of silver-donating
      antimicrobial dressings for venous leg ulcers (VULCAN trial) (Br J Surg 2009; 96:
      1147-1156).

PMID- 20140945
TI  - Multicentre analysis of oncological and survival outcomes following anastomotic
      leakage after rectal cancer surgery (Br J Surg 2009; 96: 1066-1075).

PMID- 20140947
TI  - Sentinel lymph node biopsy in breast cancer guided by indocyanine green
      fluorescence (Br J Surg 2009; 96: 1289-1294).

PMID- 20140948
TI  - Optimizing the outcome of surgery in patients with rectal cancer and synchronous
      liver metastases (Br J Surg 2010; 97: 383-390).

PMID- 20140949
TI  - Randomized clinical trial to compare the effects of preoperative oral
      carbohydrate versus placebo on insulin resistance after colorectal surgery (Br J
      Surg 2010; 97: 317-327).

PMID- 20140950
TI  - Hepatitis B virus infection among American patients with chronic hepatitis C
      virus infection: prevalence, racial/ethnic differences, and viral interactions.
AB  - Little is known about hepatitis B virus (HBV) infection among patients with
      chronic hepatitis C virus (HCV) infection in the United States. We prospectively
      enrolled 1,257 patients with chronic HCV infection from two medical centers in
      New York City. A total of 61.5% (95% confidence interval, 58.8%-64.2%) had
      evidence of prior exposure to HBV (hepatitis B core antibody-positive), whereas
      5.8% (95% confidence interval, 4.5%-7.1%) had dual infection with HBV (hepatitis
      B surface antigen-positive). Multivariable logistic regression analysis
      identified age <40 years, Asian race, injection drug use, and a greater number of
      lifetime sexual partners as independent risk factors for HBV-HCV dual infection.
      Liver biopsy results in 26 HBV-HCV-infected and 658 HCV-monoinfected patients
      showed that stage 3 or 4 fibrosis was significantly more common in those with HBV
      HCV dual infection (84.6% versus 29.9%; P < 0.001). Patients infected with HBV
      and HCV had significantly lower median HCV RNA levels (1.3 versus 4.5 x 10(6)
      copies/mL; P < 0.001) and were less likely to have HCV RNA levels > or =5 x 10(6)
      copies/mL (12.3% versus 45.4%; P < 0.001) than those who had HCV monoinfection.
      All five patients with HBV-HCV dual infection who had undetectable HBV DNA levels
      had HCV RNA levels > or =5 x 10(6) copies/mL. CONCLUSION: American patients with
      chronic HCV infection should be tested for HBV, especially younger patients,
      Asians, injection drug users, and those with an increased number of lifetime
      sexual partners. The presence of severe liver disease and HBV-HCV viral
      interactions in patients with dual infection necessitates careful but aggressive
      clinical management, although the optimal strategy remains to be determined.

PMID- 20140951
TI  - The challenge of using randomized trials in wound healing.

PMID- 20140952
TI  - Melatonergic regulation of hemolymph sugar levels in the freshwater edible crab,
      Oziotelphusa senex senex.
AB  - In this study, the hyperglycemic effect of melatonin in the freshwater edible
      crab, Oziotelphusa senex senex, is investigated. Injection of melatonin induced
      hyperglycemia in a dose-dependent manner. Administration of melatonin produced
      hyperglycemia in both intact and eyestalk-ablated crabs. Bilateral eyestalk
      ablation resulted in significant increase in the total carbohydrates and glycogen
      levels with a significant decrease in phosphorylase activity in the
      hepatopancreas and muscle of the crabs. Injection of melatonin resulted in
      significant decrease in the total carbohydrate and glycogen levels, with an
      increase in phosphorylase activity in hepatopancreas and muscle of both intact
      and eyestalk-ablated crabs. From the results, it is hypothesized that melatonin
      induced hyperglycemia in the crab, O. senex senex, is not mediated by eyestalk
      hyperglycemic hormone.

PMID- 20140953
TI  - Deletion at chromosome arm 9p in relation to BRAF/NRAS mutations and prognostic
      significance for primary melanoma.
AB  - We report an investigation of gene dosage at 9p21.3 and mutations in BRAF and
      NRAS, as predictors of relapse and histological markers of poor melanoma
      prognosis. Formalin-fixed primary melanomas from 74 relapsed and 42 nonrelapsed
      patients were sequenced for common BRAF and NRAS mutations (N = 71 results) and
      gene dosage at 9p21.3 including the genes CDKN2A (which encodes CDKN2A and
      P14ARF), CDKN2B (CDKN2B), and MTAP was measured using multiplexed ligation
      dependant probe amplification (MLPA), (N = 75 results). BRAF/NRAS mutations were
      detected in 77% of relapsers and 58% of nonrelapsers (Fisher's exact P = 0.17),
      and did not predict ulceration or mitotic rate. There was no relationship between
      BRAF/NRAS mutations and gene dosage at 9p21.3. Reduced gene dosage at MTAP showed
      a borderline association with BRAF mutation (P = 0.04) and reduced gene dosage at
      the interferon gene cluster was borderline associated with wild type NRAS (P =
      0.05). Reduced gene dosage in the CDKN2A regions coding for CDKN2A was associated
      with an increased risk of relapse (P = 0.03). Reduced gene dosage across 9p21.3
      was associated with increased tumor thickness, mitotic rate, and ulceration (P =
      0.02, 0.02, and 0.002, respectively), specifically in coding regions impacting on
      CDKN2B and P14ARF and CDKN2A. Loss at MTAP (P = 0.05) and the interferon gene
      cluster (P = 0.03) on 9p21 was also associated with tumor ulceration. There was
      no association between reduced gene dosage at 9p21.3 and subtype or site of
      tumor. This study presents supportive evidence that CDKN2B, P14ARF, and CDKN2A
      may all play a tumor suppressor role in melanoma progression.

PMID- 20140954
TI  - TWIST1 hypermethylation is observed frequently in colorectal tumors and its
      overexpression is associated with unfavorable outcomes in patients with
      colorectal cancer.
AB  - Although growing evidence demonstrates that TWIST1 is an interesting tumor
      biomarker, little is known about the clinical significance of TWIST1 expression
      and TWIST1 methylation in human primary colorectal cancer. In this study, we
      examined the association of TWIST1 expression and TWIST1 methylation with
      clinicopathologic features in human primary colorectal tumors. Primary colorectal
      cancer (CRC) specimens from 319 patients, corresponding normal colorectal
      nontumorous mucosa from 251 patients with cancer, and colorectal adenomas from
      189 patients were used. Methylation and expression levels of TWIST1 were compared
      with clinicopathologic features. The TWIST1 methylation level was higher in
      colorectal adenoma and cancer than in normal colorectal mucosa. Elevated TWIST1
      mRNA expression in normal colorectal mucosa in patients with CRC as well as in
      primary CRC specimens was associated with unfavorable outcomes. There was no
      correlation between TWIST1 methylation and TWIST1 expression. Our results suggest
      that TWIST1 methylation may be a useful biomarker for screening colorectal
      tumors. In addition, TWIST1 mRNA expression is a possible molecular marker for
      predicting the outcome in patients with CRC. Confirmatory studies using
      independent data sets are needed to confirm our findings.

PMID- 20140955
TI  - Tropical hornbills (Aceros cassidix, Aceros undulatus, and Buceros hydrocorax)
      use ballistic transport to feed with their large beaks.
AB  - The most common and plesiomorphic mechanism of food transport in tetrapods is
      lingual-based. Neognathous birds use this mechanism for exploiting a large
      diversity of food resources, whereas paleognathous birds use cranioinertial
      mechanism with or without tongue involvement. Food transport in three hornbills'
      species (Aceros cassidix, A. undulatus, and Buceros hydrocorax) is defined by a
      ballistic transport mechanism. Only one transport cycle is used for moving the
      food from the tip of the beak to the pharynx. The tongue never makes contact with
      the food nor is it used to expand the buccal cavity. In hornbills, filmed through
      high-speed video, time to food release occurred between 0.11 and 0.16 sec before
      time to maximum gape. The ballistic curves show similar patterns. Maximum gape
      angle is significantly different between the three species. Each species show a
      different kinematic and motor pattern of head movements associated with ballistic
      transport. In A. undulatus, head rotation follows a continuous pattern similar to
      that reported earlier in toucans. A. cassidix rotates head downward at the time
      of maximum gape to permit food to reach the pharynx without touching the
      mandible. B. hydrocorax elevates the head along the transport cycle to avoid
      contact with the food to the cavity of the upper beak. Selection of large food
      items in the diet may explain the evolutionary trend of using ballistic transport
      in the feeding behavior of hornbills, which play a key role in tropical forest
      ecology by dispersing seeds.

PMID- 20140956
TI  - What do population-level welfare indices suggest about the well-being of zoo
      elephants?
AB  - To assess zoo elephants' welfare using objective population-level indices, we
      sought data from zoos and other protected populations (potential "benchmarks") on
      variables affected by poor well-being. Such data were available on fecundity,
      potential fertility, stillbirths, infant mortality, adult survivorship, and
      stereotypic behavior. Most of these can also be affected by factors unrelated to
      well-being; therefore, for each, we analyzed the potential role of these other
      factors. Population-level comparisons generally indicate poor reproduction, and
      poor infant and adult survivorship in zoos compared with benchmark populations
      (with some differences between zoo regions and over time). Stereotypic behavior
      also occurs in c. 60% of zoo elephants; as the population-level welfare index
      least open to alternative interpretations, this represents the strongest evidence
      that well-being is/has been widely compromised. Poor well-being is a parsimonious
      explanation for the diverse range of population-level effects seen, but to test
      this hypothesis properly, data are now needed on, for example, potential
      confounds that can affect these indices (to partition out effects of factors
      unrelated to well-being), and causes of the observed temporal effects, and
      differences between species and zoo regions. Regardless of whether such
      additional data implicate poor well-being, our findings suggest that elephant
      management has generally been sub-optimal. We also discuss the selection and
      utilization of benchmark data, as a useful future approach for evaluating such
      issues.

PMID- 20140957
TI  - Internalization and intracellular trafficking of a PTD-conjugated anti-fibrotic
      peptide, AZX100, in human dermal keloid fibroblasts.
AB  - A challenge in advanced drug delivery is selectively traversing the plasma
      membrane, a barrier that prohibits the intracellular delivery of most peptide and
      nucleic acid-based therapeutics. A variety of short amino acid sequences termed
      protein transduction domains (PTDs) first identified in viral proteins have been
      utilized for over 20 years to deliver proteins nondestructively into cells,
      however, the mechanisms by which this occurs are varied and cell-specific. Here
      we describe the results of live cell imaging experiments with AZX100, a cell
      permeable anti-fibrotic peptide bearing an "enhanced" PTD (PTD4). We monitored
      fluorescently labeled AZX100 upon cell surface binding and subsequent
      intracellular trafficking in the presence of cellular process inhibitors and
      various well-defined fluorescently labeled cargos. We conclude that AZX100 enters
      cells via caveolae rapidly, in a manner that is independent of glycoconjugates,
      actin/microtubule polymerization, dynamins, multiple GTPases, and clathrin, but
      is associated with lipid rafts as revealed by methyl-beta-cylodextrin. AZX100
      treatment increases the expression of phospho-caveolin (Y14), a critical effector
      of focal adhesion dynamics, suggesting a mechanistic link between caveolin-1
      phosphorylation and actin cytoskeleton dynamics. Our results reveal novel and
      interesting properties of PTD4 and offer new insight into the cellular mechanisms
      facilitating an advanced drug delivery tool.

PMID- 20140958
TI  - Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal
      model of Alzheimer's disease.
AB  - Astrocytes are fundamental for brain homeostasis and are at the fulcrum of
      neurological diseases including Alzheimer's disease (AD). Here, we monitored
      changes in astroglia morphology throughout the age-dependent progression of AD.
      We used an immunohistochemical approach that allows us to determine the domain of
      glial cytoskeleton, by measuring the surface, volume, and the relationship
      between astrocytes and neuritic plaques. We investigated astroglia in the
      hippocampus of a triple transgenic mouse model of AD (3xTg-AD) that mimics the
      progression of the human disease. The numerical density of astrocytes is affected
      neither by AD nor by age. We found reduction of surface and volume of GFAP
      profiles from early ages (6 months; 43.84 and 52.76%, respectively), persisting
      at 12 (40.73 and 45.39%) and 18 months (64.80 and 71.95%) in the dentate gyrus
      (DG) of 3xTg-AD, whereas in CA1 it appears at 18 months (29.42 and 32.74%). This
      cytoskeleton atrophy is accompanied by a significant reduction of glial somata
      volume in DG at 12 and 18 months (40.46 and 75.55%, respectively), whereas in CA1
      it is significant at 18 months (42.81%). However, while astroglial atrophy
      appears as a generalized process, astrocytes surrounding plaques are clearly
      hypertrophic as revealed by increased surface (48.06%; 66.66%), and volume
      (57.10%; 71.06%) of GFAP profiles in DG and CA1, respectively, at 18 months. We
      suggest differential effects of AD on astroglial populations depending on their
      association with plaques accounting for the progressive disruption of neural
      networks connectivity and neurotransmitters imbalance which underlie mnesic and
      cognitive impairments observed in AD.

PMID- 20140959
TI  - Glutamine synthetase deficiency in murine astrocytes results in neonatal death.
AB  - Glutamine synthetase (GS) is a key enzyme in the "glutamine-glutamate cycle"
      between astrocytes and neurons, but its function in vivo was thus far tested only
      pharmacologically. Crossing GS(fl/lacZ) or GS(fl/fl) mice with hGFAP-Cre mice
      resulted in prenatal excision of the GS(fl) allele in astrocytes. "GS-KO/A" mice
      were born without malformations, did not suffer from seizures, had a suckling
      reflex, and did drink immediately after birth, but then gradually failed to feed
      and died on postnatal day 3. Artificial feeding relieved hypoglycemia and
      prolonged life, identifying starvation as the immediate cause of death. Neuronal
      morphology and brain energy levels did not differ from controls. Within control
      brains, amino acid concentrations varied in a coordinate way by postnatal day 2,
      implying an integrated metabolic network had developed. GS deficiency caused a 14
      fold decline in cortical glutamine and a sevenfold decline in cortical alanine
      concentration, but the rising glutamate levels were unaffected and glycine was
      twofold increased. Only these amino acids were uncoupled from the metabolic
      network. Cortical ammonia levels increased only 1.6-fold, probably reflecting
      reduced glutaminolysis in neurons and detoxification of ammonia to glycine. These
      findings identify the dramatic decrease in (cortical) glutamine concentration as
      the primary cause of brain dysfunction in GS-KO/A mice. The temporal dissociation
      between GS(fl) elimination and death, and the reciprocal changes in the cortical
      concentration of glutamine and alanine in GS-deficient and control neonates
      indicate that the phenotype of GS deficiency in the brain emerges coincidentally
      with the neonatal activation of the glutamine-glutamate and the associated
      alanine-lactate cycles.

PMID- 20140961
TI  - Natural history and manifestations of the hypermobility type Ehlers-Danlos
      syndrome: a pilot study on 21 patients.
AB  - Hypermobility type Ehlers-Danlos syndrome (HT-EDS) is a relatively frequent,
      although commonly misdiagnosed variant of Ehlers-Danlos syndrome, mainly
      characterized by marked joint instability and mild cutaneous involvement. Chronic
      pain, asthenia, and gastrointestinal and pelvic dysfunction are characteristic
      additional manifestations. We report on 21 HT-EDS patients selected from a group
      of 40 subjects with suspected mild hereditary connective tissue disorder.
      General, mucocutaneous, musculoskeletal, cardiovascular, neurologic,
      gastrointestinal, urogynecological, and ear-nose-throat abnormalities are
      investigated systematically and tabulated. Six distinct clinical presentations of
      HT-EDS are outlined, whose tabulation is a mnemonic for the practicing clinical
      geneticist in an attempt to diagnose this condition accurately. With detailed
      clinical records and phenotype comparison among patients of different ages, the
      natural history of the disorder is defined. Three phases (namely, hypermobility,
      pain, and stiffness) are delineated based on distinguishing manifestations. A
      constellation of additional, apparently uncommon abnormalities is also
      identified, including dolichocolon, dysphonia, and Arnold-Chiari type I
      malformation. Their further investigation may contribute to an understanding of
      the pathogenesis of the protean manifestations of HT-EDS, and a more effective
      approach to the evaluation and management of affected individuals.

PMID- 20140960
TI  - Temporal dynamics of myelination in the zebrafish spinal cord.
AB  - Knowledge of the precise timing of myelination is critical to the success of
      zebrafish-based in vivo screening strategies for potential remyelination
      therapies. This study provides a systematic review of the timing of myelination
      in the zebrafish spinal cord and a critique of techniques by which it may be
      accurately assessed. The onset of myelination was found to be 3 days
      postfertilization (d.p.f.); earlier than previously reported. This coincided with
      the dorsal migration and differentiation of oligodendrocytes and the expression
      of myelin basic protein (Mbp) transcripts and protein. Our data suggests that
      immunohistochemistry with zebrafish-specific anti-Mbp from 3 d.p.f. is the
      optimal histological method for myelin visualization, while quantification of
      myelination is more reliably achieved by quantitative polymerase chain reaction
      (qPCR) for mbp from 5 d.p.f.. Transgenic fluorescent lines such as olig2:EGFP can
      be used to assess oligodendrocyte cell number at 3 d.p.f. and the development of
      new, more specific lines may enable real time visualization of myelin itself.
      Quantitative ultrastructural analysis revealed that the myelination of zebrafish
      axons is regulated according to axonal growth and not absolute axonal size. This
      study confirms the use of the zebrafish larvae as a versatile and efficient in
      vivo model of myelination and provides a platform on which future myelination
      screening studies can be based.

PMID- 20140962
TI  - Potocki-Shaffer syndrome: comprehensive clinical assessment, review of the
      literature, and proposals for medical management.
AB  - Potocki-Shaffer syndrome is a rare contiguous gene deletion syndrome due to
      haploinsufficiency of the 11p11.2p12 region and is characterized by craniofacial
      abnormalities, developmental delay, intellectual disability, multiple exostoses,
      and biparietal foramina. In this study, six patients with the Potocki-Shaffer
      syndrome were identified and evaluated using a multidisciplinary protocol that
      included assessments by a geneticist, ophthalmologist, otolaryngologist,
      orthopedist, nephrologist, audiologist, and neuropsychologist. Diagnostic studies
      included skeletal survey, magnetic resonance imaging of the brain, renal
      ultrasound, complete blood count, comprehensive metabolic panel, thyroid studies,
      and urinalysis. Using array comparative genomic hybridization, we further
      characterized the deletion in five of these patients. The results of these
      evaluations were combined with a comprehensive review of reported cases. Our data
      highlight the characteristic facial features, biparietal foramina, moderate-to
      severe developmental delay and intellectual disability, myopia and strabismus,
      and multiple exostoses seen with this disorder. We also identify for the first
      time an association of Potocki-Shaffer syndrome with sensorineural hearing loss
      and autistic behaviors. Finally, we provide recommendations for the health
      maintenance of patients with Potocki-Shaffer syndrome.

PMID- 20140963
TI  - FOXE3 plays a significant role in autosomal recessive microphthalmia.
AB  - FOXE3 forkhead transcription factor is essential to lens development in
      vertebrates. The eyes of Foxe3/foxe3-deficient mice and zebrafish fail to develop
      normally. In humans, autosomal dominant and recessive mutations in FOXE3 have
      been associated with variable phenotypes including anterior segment anomalies,
      cataract, and microphthalmia. We undertook sequencing of FOXE3 in 116 probands
      with a spectrum of ocular defects ranging from anterior segment dysgenesis and
      cataract to anophthalmia/microphthalmia. Recessive mutations in FOXE3 were found
      in four of 26 probands affected with bilateral microphthalmia (15% of all
      bilateral microphthalmia and 100% of consanguineous families with this
      phenotype). FOXE3-positive microphthalmia was accompanied by aphakia and/or
      corneal defects; no other associated systemic anomalies were observed in FOXE3
      positive families. The previously reported c.720C > A (p.C240X) nonsense mutation
      was identified in two additional families in our sample and therefore appears to
      be recurrent, now reported in three independent microphthalmia families of varied
      ethnic backgrounds. Several missense variants were identified at varying
      frequencies in patient and control groups with some apparently being race
      specific, which underscores the importance of utilizing race/ethnicity-matched
      control populations in evaluating the relevance of genetic screening results. In
      conclusion, FOXE3 mutations represent an important cause of nonsyndromic
      autosomal recessive bilateral microphthalmia.

PMID- 20140964
TI  - De novo triple segmental aneuploid of 1p, 1q, and 4q in a girl with hypertrophic
      cardiomyopathy, muscle hypotonia, and multiple congenital anomalies.

PMID- 20140965
TI  - Phenotypic manifestations and management of hyperostosis cranialis interna, a
      hereditary bone dysplasia affecting the calvaria and the skull base.
AB  - Hyperostosis cranialis interna is a hereditary bone disorder that is
      characterized by endosteal hyperostosis and osteosclerosis of the calvaria and
      the skull base (OMIM 144755). The progressive bone overgrowth causes entrapment
      and dysfunction of cranial nerves I, II, V, VII, and VIII, its first symptoms
      often presenting during the second decade. This study analyzes the clinical
      course of 13 affected individuals of three related families (32 individuals). The
      disorder appears to have an autosomal-dominant transmission pattern. Facial and
      vestibulocochlear nerve dysfunction are most frequently reported. Surgical
      decompression of the accessible impaired cranial nerves is advised in the early
      symptomatic period or even in the presymptomatic period in high-risk individuals.

PMID- 20140966
TI  - Cloning and characterization of a new gene from the PAT protein family, in a
      marsupial, the stripe-faced dunnart (Sminthopsis macroura).
AB  - Recent studies of PAT proteins in Drosophila and Xenopus have revealed
      significant roles for this family of proteins in the polarized transport of lipid
      droplets and maternal determinants during early embryogenesis. In mammals, PAT
      proteins are known to function mainly in lipid metabolism, yet research has yet
      to establish a role for PAT proteins in mammalian embryogenesis. Oocytes and
      early cleavage stages in Sminthopsis macroura show obvious polarized cytoplasmic
      distribution of organelles, somewhat similar to Drosophila and Xenopus,
      suggesting that a PAT protein may also be involved in S. macroura embryonic
      development. In the present study, we identified a new marsupial gene for PAT
      family proteins, DPAT, from S. macroura. Expression analyses by RT-PCR and whole
      mount fluorescent in situ hybridization revealed that DPAT expression was
      specific to oocytes and cleavage stage conceptuses. Analysis of the localization
      of lipid droplets during S. macroura early embryonic development found a
      polarized distribution of lipid droplets at the two- and four-cell stage, and an
      asymmetric enrichment in blastomeres on one side of conceptuses from two- to
      eight-cell stage. Lipid droplets largely segregate to pluriblast cells at the 16
      cell stage, suggesting a role in pluriblast lineage allocation.

PMID- 20140967
TI  - Divergent regulation of angiopoietin-1 and -2, Tie-2, and thrombospondin-1
      expression by estrogen in the baboon endometrium.
AB  - Estrogen has an important role in the reconstruction of a new vascular network in
      the endometrium during each menstrual cycle; however, the underlying mechanisms
      are incompletely understood. Angiopoietin-1 (Ang-1) promotes vessel assembly,
      whereas Ang-2 and thrombospondin-1 (TSP-1) cause vessel breakdown. To determine
      the potential effect of estrogen on the expression of these angioregulatory
      factors in the endometrium, Ang-1, Ang-2, TSP-1, and Tie-2 receptor mRNA levels
      were assessed by real-time reverse transcriptase polymerase chain reaction in
      glandular epithelial and stromal cells isolated from the endometrium of
      ovariectomized baboons treated acutely with estradiol. Corresponding protein
      expression was assessed by immunocytochemistry and the proximity ligation assay
      (PLA) during advancing stages of the baboon menstrual cycle. Serum estradiol
      levels in ovariectomized baboons were 400 pg/ml within 4-6 hr of estradiol
      treatment. Ang-1 mRNA levels in glandular epithelial cells increased threefold (P
      < 0.01) within 4 hr of estradiol administration. In contrast, TSP-1 mRNA levels
      decreased four- to fivefold (P < 0.01) in endometrial glandular epithelial and
      stromal cells 4-6 hr after estradiol, whereas Ang-2 and Tie-2 expression was
      unaltered. Immunostaining for Ang-1 increased, TSP-1 decreased, and Ang-2 and Tie
      2 were unaltered in the endometrium during the secretory compared with the
      proliferative phase of the cycle. Endometrial Ang-1 protein expression,
      quantified by PLA, increased 10-fold (P < 0.05) between the early proliferative
      and late proliferative/mid-secretory phases of the menstrual cycle in association
      with the rise in estrogen. In summary, estrogen induced a rapid, divergent, and
      cell-specific change in expression of angiostimulatory and angioinhibitory growth
      factors in the endometrium of the nonhuman primate.

PMID- 20140968
TI  - Low-cost, high-throughput, automated counting of bacterial colonies.
AB  - Research involving bacterial pathogens often requires enumeration of bacteria
      colonies. Here, we present a low-cost, high-throughput colony counting system
      consisting of colony counting software and a consumer-grade digital camera or
      document scanner. We demonstrate that this software, called "NICE" (NIST's
      Integrated Colony Enumerator), can count bacterial colonies as part of a high
      throughput multiplexed opsonophagocytic killing assay used to characterize
      pneumococcal vaccine efficacy. The results obtained with NICE correlate well with
      the results obtained from manual counting, with a mean difference of less than
      3%. NICE is also rapid; it can count colonies from multiple reaction wells within
      minutes and export the results to a spreadsheet for data processing. As this
      program is freely available from NIST, NICE should be helpful in bacteria colony
      enumeration required in many microbiological studies, and in standardizing colony
      counting methods.

PMID- 20140969
TI  - Enumeration and phenotypic assessment of human plasmacytoid and myeloid dendritic
      cells in whole blood.
AB  - Traditionally, flow cytometry analysis of dendritic cells (DC) has followed a
      negative selection procedure, often limiting the characterization of individual
      DC subsets to enumeration. We demonstrate the development, evaluation, and
      clinical application of a novel 6 color/8 parameter flow cytometry panel to allow
      enumeration and monitoring of activation status of circulating human myeloid
      (MDC1) and plasmacytoid (PDC) dendritic cells in human whole blood. Enumeration
      showed a trend of greater numbers of MDC1s and PDCs being collected for fresh
      whole blood than frozen PBMCs, with this difference being statistically
      significant (P = 0.04) for unstimulated PDC enumeration. Intra-assay variation
      had a coefficient of variation <10% and interassay results between operators
      showed good correlation (r > 0.95). Our results on fresh whole blood showed a
      significant up regulation of CD83 on both MDC1 and PDC at 4 h post Toll-like
      ligand stimulus and this activity was comparable in frozen PBMC samples.
      Comparison for the late activation marker CCR7 showed a significant difference (P
      <0.05) in expression between fresh and frozen samples, precluding its use for
      batch analysis of frozen samples. In addition, the level of activation is
      dependent on the anticoagulant used for sample collection. For CD83 expression at
      4 h both EDTA and lithium heparin samples are comparable for MDC1 and PDC
      populations. Whereas for CCR7 expression, lithium heparin is preferable as EDTA
      increases the background expression in PDC, preventing further functional
      assessments. We demonstrate the importance of establishing the kinetic profile of
      activation marker expression and the importance of evaluating sample collection
      tubes and sample type before application of novel cytometry panels to a clinical
      study. We have shown that this DC enumeration flow cytometry panel is a robust
      analysis system that allows the flexibility of including activation markers.

PMID- 20140970
TI  - Formulation and biopharmaceutical evaluation of a transdermal patch containing
      letrozole.
AB  - The purpose of this study was to formulate a drug-in-adhesive (DIA) transdermal
      patch containing letrozole, a third generation aromatase inhibitor for the
      treatment of breast cancer, using pressure-sensitive-adhesives (PSAs) and to
      evaluate the percutaneous penetration and pharmacokinetics of letrozole after
      transdermal administration, compared with that for the oral route. The
      formulation factors for such a patch, including the PSAs, enhancers and amount of
      drug loaded were investigated. Among the tested preparations, the formulation
      with DURO-TAK 87-4098, Azone and propylene glycol showed the highest letrozole
      permeation. The pharmacokinetic characteristics of an optimized DIA patch
      containing letrozole were determined using rats, while orally administered
      letrozole in solution was used as a control. The pharmacokinetic parameter, such
      as the mean residence time (MRT) was significantly (p<0.05) different following
      transdermal administration compared with oral administration. The in vivo results
      observed with the patches in rats were in good agreement with the plasma
      concentrations predicted from the in vitro penetration data. As a patient
      friendly, convenient, high local drug concentration and sustained dosing
      therapeutic system, the transdermal patches incorporating letrozole provide a
      useful strategy for the prevention and treatment of breast cancer.

PMID- 20140972
TI  - Using an ultrapure 4He spike in tritium measurements of environmental water
      samples by the 3He-ingrowth method.

PMID- 20140973
TI  - MR molecular imaging of HER-2 in a murine tumor xenograft by SPIO labeling of
      anti-HER-2 affibody.
AB  - In vivo molecular imaging is a rapidly growing research area both for basic and
      clinical science. Non-invasive imaging of in vivo conditions at the molecular
      level increases understanding of the biological characteristics of normal and
      diseased tissues without the need for invasive surgical procedures. Among the
      various imaging modalities, magnetic resonance imaging (MRI) has garnered
      interest as a molecular imaging modality due to its high spatial resolution.
      Here, we have demonstrated that the combined use of HER-2 targeting affibody, a
      small 7 kDa molecule that behaves similarly to antibodies, and superparamagnetic
      iron oxide (SPIO) can non-invasively image HER-2 expressing cells or tissues both
      in vitro and in vivo by MRI. This preliminary study demonstrates that affibody
      SPIO is a feasible, target-specific contrast agent for in vivo MR molecular
      imaging.

PMID- 20140974
TI  - Metal dependent hydrolysis of beta-casein by sIgA antibodies from human milk.
AB  - We present the first evidence that electrophoretically and immunologically
      homogeneous sIgAs purified from milk of healthy human mothers by chromatography
      on Protein A-Sepharose and FPLC gel filtration contain intrinsically bound metal
      ions (Ca  >  Mg >= Al > Fe approximately  Zn >= Ni >= Cu >= Mn), the removal of
      which by a dialysis against ethylenediamine tetraacetic acid (EDTA) leads to a
      significant decrease in the beta-casein-hydrolyzing activity of these antibodies
      (Abs). An affinity chromatography of total sIgAs on benzamidine-Sepharose
      interacting with canonical serine proteases separates a small metalloprotease
      sIgA fraction (6.8 +/- 2.4%) from the main part of these Abs with a serine
      protease-like beta-casein-hydrolyzing activity. The relative activity of this
      metalloprotease sIgA fraction containing intrinsically bound metal ions increases
      ~1.2-1.9-fold after addition of external metal ions (Mg(2+) > Fe(2+) > Cu(2+) >=
      Ca(2+) >= Mn(2+)) but decreases by 85 +/- 7% after the removal of the
      intrinsically bound metals. The metalloprotease sIgA fraction free of intrinsic
      metal ions demonstrates a high beta-casein-hydrolyzing activity in the presence
      of individual external metal ions (Fe(2+) > Ca(2+) > Co(2+) >= Ni(2+)) and
      especially several combinations of metals: Co(2+) + Ca(2+) < Mg(2+) + Ca(2+) <
      Ca(2+) + Zn(2+) < Fe(2+) + Zn(2+) < Fe(2+) + Co(2+) < Fe(2+) + Ca(2+). The
      patterns of hydrolysis of a 22-mer oligopeptide corresponding to one of sIgA
      dependent specific cleavage sites in beta-casein depend significantly on the
      metal used. Metal-dependent sIgAs demonstrate an extreme diversity in their
      affinity for casein-Sepharose and chelating Sepharose, and interact with
      Sepharoses bearing immobilized monoclonal mouse IgGs against lambda- and kappa
      type light chains of human Abs. Possible ways of the production of
      metalloprotease abzymes (Abz) by human immune system are discussed.

PMID- 20140975
TI  - Evaluation of rHA labeled with Gd-DTPA for blood pool imaging and targeted
      contrast delivery.
AB  - A new contrast agent was developed by linking Gd-DTPA chelate to recombinant
      human albumin in the laboratory. The molar relaxivity of the new agent was tested
      in aqueous solution at B(0) 1.5 T and temperature 20 degrees C. The soluble
      compound had a higher molar longitudinal relaxivity and molar transverse
      relaxivity in water (r(1) = 7.2 s(-1) mM(-1), r(2) = 18.4 s(-1) mM(-1)) than
      those measured for Gd-DTPA solution (r(1) = 3.5 s(-1) mM(-1), r(2) = 5.5 s(-1)
      mM(-1)). The performance of the compound as a blood pool agent was investigated
      with soluble and microparticulate forms of the compound and comparisons were made
      with Gd-DTPA and the polymeric blood-pool agent, Gadomer. T(1)-weighted imaging
      experiments show that the soluble compound acts as a highly effective blood pool
      agent with hyperintensity in the vasculature persisting beyond 2 h post
      administration, compared with free Gd-DTPA, which was cleared from the blood pool
      after approximately 10 min. The clearance kinetics of the new agents were
      examined, due to the incomplete elimination within 14 days post injection; both
      rHA labeled compounds are probably not suitable for development as routine blood
      pool contrast media. However, with free sites on the Gd-loaded rHA molecule,
      there are possibilities for binding the agent to antibodies in the laboratory,
      which was demonstrated, and thus there exist potential applications for in vivo
      molecular imaging with this agent.

PMID- 20140976
TI  - Optimization of N-methyl-N-[tert-butyldimethylsilyl]trifluoroacetamide as a
      derivatization agent for determining isotopic enrichment of glycerol in very-low
      density lipoproteins.
AB  - Stable isotope kinetic studies play an important role in the study of very-low
      density lipoprotein (VLDL) metabolism, including basic and clinical research.
      Today, [1,1,2,3,3-(2)H(5)]glycerol is the most cost-effective alternative to
      measure glycerol and triglyceride kinetics. Recycling of glycerol from glycolysis
      and gluconeogenesis may lead to incompletely labelled tracer molecules. Many
      existing methods for the measurement of glycerol isotopic enrichment involve the
      production of glycerol derivatives that result in fragmentation of the glycerol
      molecule after ionization. It would be favourable to measure the intact tracer
      molecule since incompletely labelled tracer molecules may be measured as fully
      labelled. The number of methods available to measure the intact tracer in
      biological samples is limited. The aim of this project was to develop a gas
      chromatography/mass spectrometry (GC/MS) method for glycerol enrichment that
      measures the intact glycerol backbone and is suitable for electron ionization
      (EI), which is widely available. A previously published method for N-methyl-N
      [tert-butyldimethylsilyl]trifluoroacetamide (MTBSTFA) derivatization was
      significantly improved; we produced a stable derivative and increased recovery 27
      fold in standards. We used the optimized MTBSTFA method in VLDL-triglyceride and
      found that further modification was required to take matrix effects into account.
      We now have a robust method to measure glycerol isotopic enrichment by GC/EI-MS
      that can be used to rule out the known problem of tracer recycling in studies of
      VLDL kinetics.

PMID- 20140977
TI  - Adapting by calibration the sample size of a phase III trial on the basis of
      phase II data.
AB  - The problem of estimating the sample size for a phase III trial on the basis of
      existing phase II data is considered, where data from phase II cannot be combined
      with those of the new phase III trial. Focus is on the test for comparing the
      means of two independent samples. A launching criterion is adopted in order to
      evaluate the relevance of phase II results: phase III is run if the effect size
      estimate is higher than a threshold of clinical importance. The variability in
      sample size estimation is taken into consideration. Then, the frequentist
      conservative strategies with a fixed amount of conservativeness and Bayesian
      strategies are compared. A new conservative strategy is introduced and is based
      on the calibration of the optimal amount of conservativeness - calibrated optimal
      strategy (COS). To evaluate the results we compute the Overall Power (OP) of the
      different strategies, as well as the mean and the MSE of sample size estimators.
      Bayesian strategies have poor characteristics since they show a very high mean
      and/or MSE of sample size estimators. COS clearly performs better than the other
      conservative strategies. Indeed, the OP of COS is, on average, the closest to the
      desired level; it is also the highest. COS sample size is also the closest to the
      ideal phase III sample size M(I) , showing averages and MSEs lower than those of
      the other strategies. Costs and experimental times are therefore considerably
      reduced and standardized. However, if the ideal sample size M(I) is to be
      estimated the phase II sample size n should be around the ideal phase III sample
      size, i.e. n >=2M(I) /3.

PMID- 20140978
TI  - Emerging trends.  HIV is leading cause of death among younger women, WHO says.

PMID- 20140979
TI  - Treatment.  Feelings of stigmatization may discourage proper HIV care.

PMID- 20140980
TI  - SSI.  ALJ awards disability payments to deceased man's mother.

PMID- 20140981
TI  - ADA.  Employee allowed to proceed with HIV disability lawsuit.

PMID- 20140982
TI  - Antiretroviral rounds.  When your patient is too busy to take meds.

PMID- 20140983
TI  - World HIV treatment making progress, but domestic AIDS agenda floundering. 
      Funding cuts could make everything worse.

PMID- 20140984
TI  - Fatigue chief complaint?  A surprising explanation.

PMID- 20140985
TI  - Social support research provides clues to possible adherence strategies.  Study
      looks at its impact.

PMID- 20140986
TI  - Detecting highly transmissible acute HIV.  CDC: NY success may lead to national
      effort.

PMID- 20140987
TI  - Condom wrap-up, new options for prevention.

PMID- 20140988
TI  - Fatal H1N1 infection in an HIV positive woman.  Negative flu tests, HIV infection
      delay treatment.

PMID- 20140989
TI  - FDA notifications.  Combination lamivudine and tenofovir tablet approved.

PMID- 20140990
TI  - HIV/AIDS programmes for Latino communities in the USA.

PMID- 20140992
TI  - [Urinary epithelial cancer].

PMID- 20140991
TI  - [Renal cell carcinoma].

PMID- 20140993
TI  - [Chemical prevention of prostatic neoplasms].

PMID- 20140994
TI  - [Current trend in the treatment of stage I testicular tumor].

PMID- 20140995
TI  - [Specific parameters of blood lipid spectrum in adolescents with various forms of
      hypertension].
AB  - Lipid metabolic parameters were studied in 45 adolescents aged 14-17 years with
      labile or persistent hypertension. The concentration of atherogenic lipid
      fractions, such as very low-density lipoproteins and triglycerides was found to
      be significantly higher in the study group than that in the control groups. In
      the hypertension groups, the atherogeneity index was statistically more
      significant that in the controls. At the early stage of the pathological process,
      increased atherogenic fractions are a risk factor of hypertension in adolescents.

PMID- 20140996
TI  - [Molecular mass distribution of proteins in serum and synovial fluid].
AB  - The Laemmli polyacrylamide gel protein electrophoresis method was used to assess
      the protein molecular mass distribution in the serum and synovial fluid from
      apparently healthy individuals and patients with knee osteoarthritis of various
      etiologies. The development of inflammatory complications in joint diseases was
      shown to be identified on the protein separation spectra as a rise in the
      synovial fluid concentration of protein fractions with the extremely low
      molecular mass (to 20 kD). The protein molecular mass distribution in the sera in
      all the groups and that in the synovial fluid from the apparently healthy joints
      were virtually equal.

PMID- 20140997
TI  - [Relationships between serum content of tocopherol, retinol, and reproductive
      hormones in children].
AB  - Changes in the relations between the blood levels of vitamins E, A, and the
      hormones of the pituitary-gonad hormones (gonadotropic, sex steroid hormones)
      were studied in children at different pubertal stages. It has been found that at
      different pubertal stages, there is a change in the correlations the nature of
      which is determined by the relation to the blood concentrations of vitamins E and
      A.

PMID- 20140998
TI  - [Role of three-color flow cytofluorometry in the algorithm for detection of
      minimal residual disease in children with acute lymphoblastic and acute
      myeloblastic leukemia].
AB  - Three-color flow cytofluorometry (FCF) was used to identify minimal residual
      disease in 124 patients with acute lymphoblastic leukemia (ALL) treated in
      accordance with the ALL-myeloblastic leukemia (MBL)-2002/2008 protocol and 36
      patients with MBL treated under the MBL-MM-2000 protocol. It was shown that
      approximately a fifth of children with ALL, 3-color FCF could not monitor minimal
      residual disease, which required the use of 4- or more-color FCF and parallel
      determination in these MBL samples by molecular genetic methods. An algorithm of
      study of MBL by FCF, by additionally using molecular genetic methods, is
      presented.

PMID- 20140999
TI  - [Value of dynamic study of cytokines in serum and leukocytes in patients with
      acute leukemia].
AB  - A number of interleukins and iron metabolic parameters were studied in acute
      leukemia over time. Regulation of hemopoiesis and the cytokine network has been
      found to be impaired, which appears as the increased synthesis of ferritin and
      hepsidin by macrophages that are activated by imbalance in the cytokine network.
      A severe impairment of the parameters responsible for a regulatory process is
      shown to occur in leukemia. There is no complete normalization of these
      parameters during hematological remission, which is likely to lead to a further
      relapse of leukemic process.

PMID- 20141000
TI  - [Significance of considering hemoglobin derivatives and acid-base balance in the
      evaluation of the blood oxygen-transport system].
AB  - Factor analysis was used to study the pattern of relationships of a number of
      hematological parameters in clinically healthy young subjects and in patients
      with moderate anemia. The level of total hemoglobin and the concentration of red
      blood cells were ascertained to control blood oxygen-transporting function in not
      full measure and these might be referred to as basic characteristics only
      conventionally. To clarify the picture, these criteria should be supplemented by
      the information on other parameters. It is concluded that the introduction of the
      ratio of a number of hemoglobin derivatives, blood oxygen regimen and acid-base
      balance can substantially increase the validity of clinical opinions as to this
      blood function.

PMID- 20141001
TI  - [Novel immunoassay for laboratory assessment of the erythron state].
AB  - The paper presents the results of a study of embryonic or primitive hemoglobin
      (HbP), by using the authors' developed immunodiffusion monovalent test system in
      the neonatal umbilical blood and in girls than in the boys. HbP was also detected
      in patients with erythema (66.7%) and acute myeloleukemia (22.22%), it was absent
      in those with chronic lympholeukemia. The findings suggest that the early
      antenatal type of hemoglobin is likely to be of diagnostic value in assessing the
      degree of hypoxia in the differential diagnosis of hemoblastoses.

PMID- 20141002
TI  - [Fibrinogen determination by the Clauss method. Reagents and analyzers].
AB  - The Clauss method was recommended by the WHO to measure plasma fibrinogen levels.
      The purpose of this study was to assess the application of test systems made by
      the RENAM Research-and-Production Association (Moscow) on different types of
      clinical laboratory analyzers to measure fibrinogen by the Clauss method. The
      calibration line is shown to be of major value in obtaining correct results on
      each coagulometer. The findings suggest the accuracy and reproducibility of the
      determination of fibrinogen concentrations by the Clauss when the REHAM test
      systems are used to measure fibrinogen concentrations on various analyzers if
      accurate calibration lines are obtained.

PMID- 20141003
TI  - [Comparative analysis of ViroSeq and Trugene HIV-1 genotyping systems in the
      application to the virus variants in Russia].
AB  - The ViroSeq (Celera Diagnostics) and Trugene (Bayer HealthCare) HIV-1 genotyping
      systems are widely used today in world clinical practice to detect drug
      resistance mutations resulting from ineffective treatment for HIV infection. Only
      the former test has gained acceptance. The present study has compared ViroSeq and
      Trugene genotyping systems used to identify both mutations of drug resistance and
      those of polymorphism in the HIV variants circulating in Russia where the unique
      strain IDU-A prevails. Analysis of 18 samples from HIV-infected patients who
      received and did not receive specific therapy has demonstrated that the agreement
      of the results of the tests was 95% (180 of the 190 mutations). At the same time,
      the results of resistance mutation detection by the ViroSeq and Trugene HIV-1
      genotyping systems coincided completely. The fact that the Trugene HIV-1
      genotyping system may be used along with the ViroSeq test system in clinical
      diagnostic laboratories is shown in the paper.

PMID- 20141004
TI  - [The prevalence and clinicoepidemiological characteristics of diseases caused by
      streptococcus group A in Russia].
AB  - AIM: to assess the significance of Streptococcus group A (SGA) infection in
      Moscow and the Russian Federation (RF). MATERIALS AND METHODS: The materials
      contained in the 1996-2007 annual official statistical records (forms Nos. 12,
      14, 16-BH, C-51, of the State Committee for Statistics) were analyzed. RESULTS
      AND DISCUSSION: An average of 3.1 million (207.1 per 10,000 population) cases of
      SGA infection were annually notified in Russia. In the latter, the average annual
      rates of the incidence and prevalence of SGA infection (other than scarlet fever)
      in all age groups were much greater than those in Moscow. The average annual
      incidence of rheumatism was 5.1 and 6.0 per 10,000 in the RF and Moscow,
      respectively. The cases and days of temporary disability in Moscow were 2-3 times
      lower than those in the RF. The incidence and prevalence of other forms of SGA
      infection among the RF population significantly increased from 1 to 4%. In
      Moscow, there was a significant reduction in the incidence and prevalence of
      renal diseases, a decrease in the incidence of chronic rhinitis, nasopharyngitis,
      and sinusitis and in their prevalence. The prevalence of chronic tonsillitis,
      adenoiditis and paratonsillar abscesses tended to increase while their incidence
      showed no significant changes. CONCLUSION: Despite the significant declining
      trends for its incidence, prevalence, temporary disability, and mortality, SGA
      infection continues to cause a substantial socioeconomic damage and to remain to
      be one of the urgent public health problems of the country.

PMID- 20141005
TI  - [Bile biochemical composition changes in patients with chronic viral hepatitis].
AB  - AIM: to study the biochemical composition of cystic and hepatic bile in patients
      with different forms of viral hepatitis. SUBJECTS AND METHODS: Four hundred and
      fifty-seven patients with different forms of viral hepatitis were examined. The
      concentration and debit of cholic acid (CA), total cholesterol, total bilirubin,
      phospholipids, calcium, and C-reactive protein were determined by a bile
      biochemical study. Cholate-cholesterol and phospholipid-cholesterol ratios were
      simultaneously calculated for each bile portion. RESULTS: CA levels and cholate
      cholesterol ratios were significantly decreased in all patients with viral
      hepatitis. The findings suggest that duodenal digestion was impaired, CA
      secretion was lowered and the majority of patients with viral hepatitis had
      biliary insufficiency. CONCLUSION: Stepwise chromatic duodenal intubation should
      be used, by making a biochemical study of bile portions and calculating the total
      debit of bile components secreted per hour after administration of a stimulus, in
      order to make a complex diagnosis of exocrine function of the liver in patients
      with viral hepatitis.

PMID- 20141006
TI  - [Antiphospholipid syndrome at the onset of clinical manifestations of chronic
      autoimmune hepatitis of type I].
AB  - The paper describes a case of chronic autoimmune hepatitis of type I (CAH-I) that
      showed an onset accompanied by the antiphospholipid syndrome (APS). At the same
      type, CAH-I ran without both clinical manifestations and the major laboratory
      syndrome - cytolytic one, which substantially made the diagnosis of a hepatic
      disease difficult. It is concluded that the clinical manifestations fitting into
      the APS necessitates meticulous clinical, laboratory, and instrumental studies to
      find out the underlying disease.

PMID- 20141007
TI  - [Immune mechanisms of comorbidity of HIV infection and pulmonary tuberculosis].
AB  - AIM: to study the immune system in patients with tuberculosis-associated HIV
      infection at different stages of disease and during antiretroviral therapy
      (ARVT). SUBJECTS AND METHODS: The study included 90 patients with tuberculosis
      associated HIV infection; a control group comprised 117 HIV-infected patients.
      The total number of T lymphocytes and their subpopulations (CD3+, CD4+, and CD8+)
      and the levels of the cytokines TNF-alpha, IL-6, and their soluble receptors
      SRp55 of TNF-alpha (type I), SRp75 of TNF-alpha (type II), and SR of IL-6 in the
      serum. RESULTS: T-cell immunodeficiency was detected at all stages of HIV
      infection accompanied by CD3+ and CD4+ cell deficiency and decreased
      immunoregulatory index. The cytokine profile changes were indicative of a more
      noticeable reduction in the functional activity of T helper cells type I in
      patients with HIV-associated tuberculosis. CONCLUSION: The efficiency of ARVT in
      patients with HIV-associated tuberculosis was confirmed by a lower viral load and
      higher CD4+ cells. Heterodirectional changes in the content of cytokines and
      their receptors characterized by a considerable increase in the levels of TNF
      alpha, IL-6, SR of TNF-alpha and a drastic reduction in the level of SR of IL-6
      may be considered as a marker of immune recovery.

PMID- 20141008
TI  - [Effect of ascorbic acid and emoxypin on the efficiency of complex chemotherapy
      for infiltrative pulmonary tuberculosis].
AB  - AIM: to evaluate the effect of ascorbic acid and emoxypin on the efficiency of
      complex chemotherapy for infiltrative pulmonary tuberculosis. SUBJECTS AND
      METHODS: One hundred patients with infiltrative pulmonary tuberculosis in a phase
      of decay were examined. The patients were divided into 3 groups. Group 1 received
      the standard therapy (n = 34); Groups 2 (n = 33) and 3 (n = 33) had additionally
      daily intravenous dropwise infusions of ascorbic acid (500 mg) (OAO
      "Novosibkhimpharm") or emoxypin (150 mg) (Moscow Endocrine Plant). The drugs were
      injected for 10 days. Therapeutic efficiency was evaluated during 12 months.
      RESULTS: Additional use of ascorbic acid decreased the likelihood of progression
      of the disease to fibrocavernous tuberculosis and promotes a good completion of
      12-month course of therapy providing small posttuberculous changes. The
      administration of emoxypin contributes to eradication of Mycobacterium
      tuberculosis, reduces the time of decay cavity closure and a need for surgical
      treatment of pulmonary tuberculosis. CONCLUSION: The findings show it expedient
      to include ascorbic acid and emoxypin into the combined treatment regimen for
      infiltrative tuberculosis in a phase of decay.

PMID- 20141009
TI  - [Clinical and prognostic criteria for different forms and types of the course of
      Yersinia infection].
AB  - AIM: to reveal the prognostically significant symptom complexes of
      pseudotuberculosis/yersiniasis in their different forms and types. SUBJECTS AND
      METHODS: A comprehensive examination and a long-term follow-up were made in 295
      patients with yersiniasis and pseudotuberculosis. A special score scale was
      developed to evaluate the prognostic value of their clinical symptoms. RESULTS:
      The symptom complexes prognostically significant to the outcome of Yersinia
      infection were found. CONCLUSION: The use of the described prognostically
      significant symptom complexes of Yersinia infection makes it possible to
      correctly evaluate the course of the disease in each case, identify risk-group
      patients, and to use adequate treatment.

PMID- 20141010
TI  - [Hemostatic disorders and their implication in the pathogenesis of Astrakhan
      rickettsial fever].
AB  - AIM: to define a role of hemostatic disorders in the pathogenesis of Astrakhan
      rickettsial fever (ARL). SUBJECTS AND METHODS: Platelet functional activity and
      plasma hemostatic parameters were studied in 89 patients of moderate ARL.
      RESULTS: The clinical manifestations of hemostatic disorders at the height of ARL
      were characterized by the appearance of typhoid maculopapular rashes in 91.4% of
      the patients, solitary elements of which were transformed to petechiae in 20% of
      cases. At convalescence (on day 10.2 +/- 1.3 of the disease), all eruptions
      regressed via pigmentation. At the peak of the fever, there were nasal
      hemorrhages and bleedings from the sites of injections; lowered platelet
      aggregation was detectable in the presence of thrombocytopenia at the height.
      Coagulation hemostasis changes were characterized only by elevated fibrinogen
      levels. Increased platelet functional activity and decreased fibrinogen
      concentrations were observed at convalescence. CONCLUSION: The basis of the
      clinical manifestations of ARL is hemostatic disorders due to thrombocytopenia
      and diminished platelet functional activity. In early convalescence, there was
      improved platelet aggregatability; however, the increasing trend for the rate of
      aggregation and the radius of aggregates suggests a risk of thrombogenesis in
      convalescents, which requires their follow-up with obligatory hemostatic
      monitoring.

PMID- 20141011
TI  - [Optimization of use of beta-adrenoblockers in the treatment of chronic heart
      failure in the outpatient setting].
AB  - AIM: to evaluate of the effectiveness of switching from beta-adrenoblockers (BAB)
      non-included into the guidelines for the management of chronic heart failure
      (CHF) to nebivolol and bisoprolol for outpatients. SUBJECTS AND METHODS: The
      study included 67 patients with stable Functional Classes (FC) II and II CHF who
      received the standard therapy and BAB non-included into the guidelines for the
      management of CHF. The patients were randomized to the groups taking bisoprolol
      (n = 35) or nebivolol (n = 32) in doses of 1.25 to 10 mg/day. Before and 6 months
      after therapy, the investigators assessed the patient's clinical status and
      quality of life (QL), performed a six-minute walk test and echography, and
      determined the blood level of the N-terminal fragment of brain natriuretic
      peptide prohormone (NT-proBNP). RESULTS: The switching to bisoprolol and
      nebivolol was followed by a significant clinical improvement, a larger covered
      distance, and better QL. Left ventricular ejection fraction was increased along
      with a reduction in mean FC CHF. There were no significant changes in NT-proBNP
      in the total patient group, but it was significantly decreased in the subgroup of
      those with the baseline high level of the peptide. CONCLUSION: The switching of
      patients with stable CHF from therapy with BAB not included into the guidelines
      for the management of CHF to nebivolol or bisoprolol yields positive results and
      improves left ventricular systolic function (which is attended by the reduction
      in NT-proBNP levels) and may be recommended for treatment in the outpatient
      setting.

PMID- 20141012
TI  - [The degree of cognitive disorders and related psychovegative and hemodynamic
      impairments in patients with essential hypertension].
AB  - AIM: to study the specific features of clinical, hemodynamic, and
      psychovegetative impairments in patients with essential hypertension (EH) in
      relation to the degree of cognitive disorders (CD). SUBJECTS AND METHODS: Seventy
      five patients with EH were examined and, according to the presence and degree of
      CD were divided into 3 groups: 1) 17 patients without cognitive deficit; 2) 35
      patients with mild CD; 3) 23 patients with moderate CD. Risk factors, clinical
      manifestations, and hemodynamic and autonomic regulation features were assessed.
      RESULTS: In EH patients without cognitive deficit, blood pressure (BP)
      corresponded to grade 1; among cerebral disorders, there was a preponderance of
      early signs of dyscirculatory encephalopathy (DEP) that were accompanied by
      subclinical anxiety disorders, preserved autonomic adaptation, and symmetrical
      blood flow in the common carotid artery (CCA) bed. Sympathetic autonomic tone and
      the occurrence of anxiety-depressive disorders were noted in EH patients with
      mild CD along with progression of cerebral disorders and impairments in the 24
      hour BP profile and hemodynamics in the CCA bed. In patients with EH and moderate
      CD, the 24-hour BP profile corresponded to grade 2 and the significant cerebral
      symptoms were associated with the significantly impaired elastotonic properties
      of the vascular wall in the CCA bed and with the presence of signs of its
      stenosis, with the increased sympathetic and central effects on cardiac rhythm,
      and with moderate anxiety-depressive disorders. CONCLUSION: In EH patients,
      moderate CD is attended by significant BP circadian rhythm disturbances, the
      functional and structural changes in the vascular wall of the CCA bed, which are
      combined with autonomic disregulation and anxiety-depressive disorders. The
      severity of the cardiac-cerebral syndrome in patients with EH should be borne in
      mind on elaborating individual and preventive programs.

PMID- 20141013
TI  - [Peptic ulcer in patients with neurotic and affective disorders: comorbidity,
      clinicoendoscopic and psychopathological features, approaches to therapy].
AB  - AIM: to study clinicoendoscopic and psychopathological relationships and the
      course of peptic ulcer (PU) in patients with neurotic and affective disorders and
      to evaluate the efficiency of psychopharmacotherapy, by applying a comprehensive
      approach to the treatment of comorbidies. SUBJECTS AND METHODS: The study covered
      245 patients aged 43.3 +/- 8.8 years from the Department of Borderline Conditions
      who had been diagnosed as having duodenal PU and gastric PU with a prevalence of
      stress-associated neurotic disorders, as well as affective and other ones.
      Clinical psychopathological and experimental psychological tests and rating
      psychometric scales were used to evaluate the patients' mental status. Somatic
      diseases were verified by endoscopic, morphological, and ultrasound diagnostic
      techniques. RESULTS: Multivariate analysis has revealed a relationship of the
      phase of an ulcerative process and age to the first manifestations of
      psychopathology, its duration, and gender. Assessment of psychopharmacotherapy in
      patients with PU has shown the high efficacy of the antidepressant of coaxil in
      the treatment of the comorbidity. CONCLUSION: The polymorphism of
      psychopathological disorders and their trend are determined by the clinical
      changes in the course of an ulcerative or erosive process. The inclusion of
      coaxil into the combined treatment regimen for PU in patients with neurotic and
      affective disorders is expedient and pathogenetically founded at all stages of a
      follow-up.

PMID- 20141014
TI  - [Comparative assessment of bile and blood cholesterol, pigment, and protein
      metabolic parameters in patients with cholelithiasis in the presence and absence
      of opisthorchiasis].
AB  - AIM: to study the regularities of lithogenesis in patients with cholelithiasis
      (CL) and opisthorchiasis. SUBJECTS AND METHODS: Fifty-one patients with CL and
      opisthorchiasis were examined. Comparison groups comprised 32 with CL without
      opisthorchiasis and 14 patients with opisthorchiasis without CL. All the patients
      underwent a comprehensive examination involving laboratory and ultrasound
      studies. RESULTS: Opisthorchis invasion leads to increases in vesicular and
      hepatic bile cholesterol saturation and bile albumin levels due to intrahepatic
      ductal cholestasis, to a rise in bile unconjugated bilirubin concentration, which
      is caused by the activation of proliferative inflammation in the bile ducts and
      by the increased deposits of bilirubin complexes resulting from higher bile
      globulin levels. CONCLUSION: In opisthorchiasis, bile lithogenic factors mostly
      activate in the development of CH in patients with significant manifestations of
      cholestasis, angiocholitis with the most preserved concentration function of the
      gallbladder.

PMID- 20141015
TI  - [Detection of distal forearm osteopenia and osteoporosis in Perm women aged 50
      years or older].
AB  - AIM: to assess the prevalence of subnormal bone mineral density (BMD) of the
      distal forearm among women living in Perm and the Perm Region, by taking into
      account the data of distal forearm X-ray densitometry and risk factors of
      osteoporosis (OP). SUBJECTS AND MATERIALS: This one-stage study included 1765
      women aged 50-90 years (mean age 61.8 years, standard deviation 8.1). All the
      participants filled in the questionnaire of the National Program of Osteoporosis
      Risk Factors Study. Radial BMD (of the radius) was estimated by X-ray
      absorptiometry on a DTX 200 unit. RESULTS: Osteopenia was detected 593 (33.6%)
      females aged 50 years or older and OP was found in 391 (22.2%). The women with
      the osteopenic syndrome had lower body weight. Those with OP showed much more
      frequently vertebral fractures and essential hypertension. Irrespective of the
      BMD, the proportion of regular dairy produce was very small. CONCLUSION: In more
      than a half of the 50-year-old or more women residing in Perm and the Perm Region
      have lower distal forearm BMD and increased risk for fractures in minimal injury.
      The proportion of women with EH is statistically significant higher among the
      women with the osteopenic syndrome.

PMID- 20141016
TI  - [Lymphocytic sensitization to insulin as a risk factor of diabetes mellitus].
AB  - AIM: to search for immunological risk factors of diabetes and prediabetes.
      SUBJECTS AND METHODS: The prospective study included 91 patients (26 males and 65
      females; mean age 45.9 years; body mass index 27 +/- 3 kg/m2). Follow-ups were
      made in 1993 to 1995 and in 2005 to 2007. All the patients were divided into 2
      groups depending on the presence or absence of an autoimmune reaction to insulin.
      The incidence of hyperglycemia, diabetes, essential hypertension, coronary heart
      disease (CHD), obesity, and inflammatory skin diseases was determined in each
      group. RESULTS: The incidence of hyperglycemia, diabetes, or CHD was much higher
      in the patients having an autoimmune reaction to insulin. An excess body weight
      of more than 30% and additional 10 years of life from the baseline increased a
      risk for diabetes in persons showing a lymphocytic sensitization to insulin, this
      was not seen in those without this responsiveness. CONCLUSION: Lymphocytic
      sensitization to insulin is a risk factor of diabetes and prediabetes. Aging,
      female sex, and overweight are provocative factors for diabetes in persons with
      an autoimmune reaction to insulin.

PMID- 20141017
TI  - [Role of tumor necrosis factor in the development of metabolic syndrome].
AB  - AIM: to study a relationship of the proinflammatory cytokine - alpha-tumor
      necrosis factor (alpha-TNF) to the values of carbohydrate and lipid metabolisms,
      lipid peroxidation, and hemorheology in patients with components of the metabolic
      syndrome (MS). SUBJECTS AND METHODS: Eighty-seven patients (35 males and 52
      females) aged 21 to 69 years were examined. Groups were formed depending on the
      number of components of MS and its existing complications. Physical examination
      was conducted; the values of lipid and carbohydrate metabolisms, lipid
      peroxidation, and hemorheology were estimated. The serum alpha-TNF levels were
      measured by enzyme immunoassay. The neural network technique was used to analyze
      the factor correlations of different types of MS. RESULTS: The estimation of a
      diversity of homeostatic parameters could ascertain the significance of the level
      of alpha-TNF in different types of MS. Its high level is associated with the
      elevated concentrations of low-density lipoprotein cholesterol (LDL-C) and
      apolipoprotein A1 (apoA1) in the presence of 1-2 risk factors for MS. In the
      individuals with 3 components of MS or more, as well as in the presence of its
      complications, the levels of alpha-TNF were closely related to those of LDL-C and
      apoA1, insulin resistance, and the changes in lipid peroxidation and hemostasis.
      CONCLUSION: The early stage of MS is marked by the higher alpha-TNF level, its
      correlation with the changes in lipid metabolism and insulin concentrations.
      Alpha-TNF may be considered not only as an early marker of a systemic
      inflammatory reaction in the development of cardiovascular events, as well as a
      risk factor for MS.

PMID- 20141018
TI  - [The extrahepatic site of hepatitis C virus: clinical manifestations and
      prognostic value].
AB  - The high incidence of recurrent chronic hepatitis C after a course of antiviral
      therapy determines the urgency of determining the extrahepatic reservoirs of
      hepatitis C virus (HCV). The most extrahepatic site for the virus is peripheral
      mononuclear cells (PMC). Assuming that there may be HCV replication in the PMC),
      these cells can be considered as a potential reservoir of HCV infection. The most
      common extrahepatic manifestation of HCV is cryoglobulinemia, the genesis of
      which may be active viral replication in the cells of the immune system. There is
      evidence that HCV is detectable just in the tissues of the involved organs. Thus,
      most systemic manifestations may be directly associated with extrahepatic HCV
      replication.

PMID- 20141019
TI  - [Prospects for treating mosquito-borne flavivirus encephalitides].
AB  - The Japanese encephalitis virus and West Nile virus belong to the family
      Flaviviridae, genus Flavivirus; they have a similar transmission cycle, with
      birds serving as the natural vertebrate host and mosquitoes, primarily, Culex
      species, both serving as the enzootic vectors and infecting humans. These
      arboviruses have caused more human cases of severe neuroinvasive disease
      worldwide during the past decade than other mosquito-borne flaviviruses. The
      current data and concepts on the clinical manifestations, pathogenesis,
      diagnosis, and treatment of infections caused by West Nile virus and Japanese
      encephalitis virus, are considered. The need for developing innovative approaches
      to etiotropic therapy for West Nile fever and Japanese encephalitis is
      emphasized; these approaches should be based on the comprehensive insight and
      extensive studies of the pathogenesis of flaviviral infections.

PMID- 20141020
TI  - [Diastolic heart failure: are problems in its diagnosis and treatment solvable?].
AB  - The paper discusses the problem of chronic heart failure (CHF) in left
      ventricular diastolic dysfunction - diastolic heart failure (DHF). It considers
      whether DHF is an independent phenotype or nothing more than a step in the
      development of systolic heart failure. The results of a number of studies
      evaluating the efficiency of treatment for DHF with angiotensin-converting enzyme
      inhibitors, angiotensin II receptor blockers, spironolactone, and beta-blockers
      are given. It is concluded that diastolic dysfunction should be necessarily kept
      in mind on examining patients with CHF.

PMID- 20141021
TI  - Royal College of Nursing, Australia--the first 60 years.

PMID- 20141022
TI  - Colonel Coralie Gerrard: a lifetime of distinction.

PMID- 20141023
TI  - The H1N1 influenza 09 and its potential impact on the Australian nursing
      workforce.

PMID- 20141024
TI  - Changing the mindset: an inter-disciplinary approach to management of the
      bariatric patient.
AB  - Obesity is a major health issue throughout the world. Modern nomenclature has
      replaced the word obesity with bariatric-related terminology. A bariatric person
      is defined as one who has health limitations due to their physical size, lack of
      mobility and environmental access. Obese people are often characterised by
      society as being lazy and unattractive, and this perception is prevalent among
      healthcare professionals also. This paper describes an innovative approach to
      obesity management in a large Australian health district in Queensland.

PMID- 20141025
TI  - Why fellowship? Peak professional bodies, peer recognition and credentialing in
      Australia.
AB  - BACKGROUND: Professions frequently distinguish themselves from trades or
      vocations, by creating professional peak bodies. Usually professional peak bodies
      offer two levels of subscription: membership and fellowship. Fellowship of a peak
      body is widely considered as offering status and prestige by recognising
      contribution made to one's profession. Fellowship therefore, often brings with it
      specific privileges of a symbolic or material nature, or both. AIM: To describe
      the criteria for eligibility for fellowship; the perceived benefits of fellowship
      to individuals from the organisations' viewpoint; the process of obtaining and
      maintaining fellowship across a range of professional peak bodies; and to apply
      the outcomes from the survey to nursing professional peak bodies. METHOD: A
      telephone survey of 25 professional organisations representing a range of
      disciplines and industries in Australia was conducted. Each organisation was
      telephoned and the manager responsible for membership was invited to participate
      in a 10-min telephone survey. RESULTS: Of the 25 organisations approached, 24
      agreed to participate (response rate 96%). For six (25%) of these participating
      organisations, membership was exclusively limited to nurses and/or midwives.
      Fellowship was offered in 22 organisations (92%). Significant professional
      experience (73%) was the most frequently cited criterion for fellowship.
      Professional leadership/contribution to the profession was listed by less than
      half (45%) organisations surveyed. Over half (55%) of those organisations that
      offered fellowship programs also were credentialing bodies. The main benefit of
      fellowship reported was the prospect of peer recognition and higher professional
      standing (77%). DISCUSSION: The majority of organisations reported offering
      fellowship status and all hadriteria for fellowship. The most frequently cited
      criteria were, however, based on longevity in the profession and continued
      financial membership rather than demonstrated leadership within the profession.
      There was variability in how fellowship was attained and maintained which may be
      linked to whether organisations have a credentialing role or not. A more in depth
      study of fellowship is warranted.

PMID- 20141026
TI  - An investigation of emotional wellbeing and its relationship to contemporary
      nursing practice.
AB  - This paper is an investigation of emotional wellbeing and its relationship to
      contemporary nursing practice for women community health nurses (CHNs) who are
      providing palliative care. Palliative care provision has been acknowledged as a
      source of job satisfaction for many nurses however emotional interactions place
      increasing strain on nurses' wellbeing. Psychosocial aspects of care are reported
      as having a personal as well as a professional impact. Work related stress places
      nurses at increased risk of harm and impaired wellbeing. An emancipatory
      methodology was chosen for this study. Semi-structured interviews and reflective
      journaling were the methods used. The data was collected over a 16-month period
      during 2006-2007. There were fifteen participants. This qualitative study
      explored Australian rural and urban community nurses' experiences with wellbeing,
      emotional work and their professional practice. The findings revealed opposing
      social forces, an inner 'dialectical' tension between the nurses' expectations of
      their professional practices and what is valued in their practice settings. In
      terms of emotional wellbeing, two overarching themes will be discussed: feeling
      balanced and feeling out of balance. Workplace environments that were not always
      conducive to healing increased the emotional strain on nurses. Nurses' work
      promotes the healing of others therefore to deny the healing of nurses' is to
      deny others of healing. The need for further qualitative research investigating
      the emotional wellbeing and professional practice of community nurses who provide
      palliative care is necessary.

PMID- 20141027
TI  - Registered nurses' and midwives' knowledge of epidural analgesia.
AB  - BACKGROUND: Despite epidural analgesia increasingly being utilized in hospitals,
      very little research-based evidence is available about registered nurses' (RNs)
      and midwives' knowledge of this technique. OBJECTIVE: To describe the current
      epidural knowledge levels of RNs and midwives in a multi-site setting. METHOD:
      RNs and midwives at four, regional teaching facilities completed an epidural
      knowledge test. The instrument included demographic items and five knowledge
      subscales relating to epidural analgesia: spinal cord anatomy and physiology;
      epidural pharmacology; complications of epidural analgesia; assessment of sensory
      and motor blockade and the general management of patients with epidural
      analgesia. RESULTS: A total of 408 (99.7% response) RNs and midwives completed
      the test. Respondents demonstrated good knowledge of sensory and motor blockade
      assessment and the general management of epidural analgesia subscales with
      correct responses to 75 and 77% of the questions in these subscales,
      respectively. Fair knowledge relating to the spinal cord anatomy and physiology
      subscale was demonstrated with 69% of the questions answered correctly. The
      knowledge subscales relating to epidural pharmacology (57% correct responses) and
      the complications of epidural analgesia (56% correct responses) were problematic
      for the sample. CONCLUSION: The research results provide generalizable
      information about what RNs and midwives know about epidural analgesia. These
      results are an important guide in the development of new and existing dedicated
      epidural education programs. The results also provide some direction for further
      research into this important topic.

PMID- 20141028
TI  - Absolutely fabulous--but are we? Carers' perspectives on satisfaction with a
      palliative homecare service.
AB  - People with terminal diagnoses are increasingly encouraged to stay at home for
      the trajectory of their illness. Consequently, relatives and friends are
      progressively undertaking the informal carer role more frequently in conjunction
      with formal palliative care teams. Although there is international literature on
      the efficacy of and satisfaction with publicly funded palliative homecare, to
      date, there is scant literature reporting satisfaction with privately funded
      palliative homecare especially in Australia. Survey and focus group methods were
      used to explore carers' levels of satisfaction with a private Australian
      palliative homecare service and to uncover unmet carer needs. There were 300
      (41.7%) responses to the survey. Three focus groups were conducted, separately
      comprising current carers, past carers and palliative homecare staff. While there
      was a high level of satisfaction with the service generally, carers identified a
      lack of knowledge about aspects of the illness and treatment course. A desire to
      have time with nursing staff independent of the patient, including continued
      contact after the death of the patient, was also expressed. Themes relating to
      service delivery concerned lack of continuity of attending nursing staff and a
      perceived inadequate number of service visits. These findings were similar to
      results reported in the literature for publicly funded services. Therefore
      interventions used in the public sector to meet carer needs are likely to be
      successful if applied in the private sector.

PMID- 20141029
TI  - Planning and development of the continuous National Survey of Family Growth.
AB  - OBJECTIVES: This report describes how the continuous National Survey of Family
      Growth (NSFG) (begun in 2006) was designed, planned, and implemented. The NSFG is
      a continuous national survey of men and women 15-44 years of age designed to
      provide national estimates of factors affecting pregnancy and birth rates; men's
      and women's health; and parenting. METHODS: The survey used in-person, face-to
      face interviews conducted by trained female interviewers. One person per
      household was interviewed from a national area probability sample. The data
      collection used computer-assisted personal interviewing (CAPI). Separate
      questionnaires were used for male and female respondents. The last section of the
      questionnaires used a self-administered technique called audio computer-assisted
      self-interviewing or ACASI. Each data collection period lasted 12 weeks-10 weeks
      for "Phase 1," the main data collection protocol, and 2 weeks for "Phase 2," an
      intensive attempt to locate and interview nonrespondents. RESULTS: Each year,
      about 5,000 persons were interviewed in about 33 areas, called primary sampling
      units (PSUs). Over a 4-year period, 110 PSUs will be used. This report gives an
      overview of the procedures used in the conduct of the continuous NSFG. A later
      report will describe response rates and other results of the data collection, but
      the early fieldwork has gone well.

PMID- 20141030
TI  - [Significance of mitotic spindle checkpoint genes in leukemia].
AB  - Leukemia is a clonal proliferative disorder of the multipotent hematopoietic stem
      cells that leads to abnormal cell growth and (or) differentiation. The hallmark
      of the disease is the presence of oncogene expression in bone marrow or
      peripheral blood as a result of some chromosome translocations. The development
      of leukemia with transfer to disease progression presents a multistage process
      implicating series of molecular changes leading to chromosomal instability and
      aneuploidy. The most possible of these changes include the followings: appearance
      of additional chromosome translocations, activation of other not previously
      expressed oncogenes, loss of tumor suppressor genes, abnormal centrosome
      duplication, and dysfunction of the genes which coordinate the accurate
      chromosome alignment and chromosome segregation during mitosis. The two latter
      molecular changes which are controlled by mitotic spindle checkpoints play the
      role in leukemogenesis and are probably involved in apoptosis.

PMID- 20141031
TI  - [Cell therapy for type I diabete].
AB  - Cell therapy is a modern and promising approach to type I diabetes mellitus
      treatment. Nowadays a wide range of cells is used in laboratory experiments and
      clinical studies, including allogeneic and xenogeneic cells of Langergance
      islets, bone marrow cells, haematopoietic stem cells, mesenchymal stem cells, and
      cord blood stem cells. Any type of the cells named could correct the status of
      the patients to a certain extent. However, full recovery after cell therapy has
      not been achieved yet.

PMID- 20141032
TI  - [Effect of alpha-lipoic acid on fibroblasts 3T3 and 3T3-SV40. Comparison with N
      acetylcysteine action].
AB  - In this study we investigated the effect of alpha-lipoic acid (ALA) in
      concentration range 0.7-5.0 mM on the intracellular level of reduced glutathione,
      the cell cycle phase distribution, the structure of microfilaments and
      microtubules of normal (3T3) and transformed (3T3-SV40) fibroblasts. We obtained
      that ALA increased the glutathione content in transformed cells, but did not
      change its level in normal cells, induced cell cycle arrest of 3T3 cells (but not
      3T3-SV40 cells), and disrupted actin microfilaments in cells of both lines. The
      effect of ALA was compared with N-acetylcysteine (NAC) action. The whole complex
      of findings allows us to affirm that each of these antioxidants acts on its own
      target molecules in normal and transformed cells and activates different signal
      and metabolic pathways in these cells. But at the same time the intermediate
      steps of ALA and NAC action can be common (alteration of the intracellular level
      of glutathione, reorganization of actin cytoskeleton, etc.).

PMID- 20141033
TI  - [Cellular repair potential in families of ataxia-telangiectasia patients].
AB  - The key protein of the global cellular response to DNA damage is proteinkinase
      ATM. Ataxia-telangiectasia (AT), a genetic disorder due to mutations in both
      alleles of ATM gene, is characterized by numerous neurological abnormalities,
      increased frequency of malignant tumors, premature ageing and increased radio
      sensitivity. AT is the most frequently found disease displaying inherited radio
      sensitivity. The data accumulated by this time on the role of the protein ATM in
      regulation of cellular response to DNA damage and detailed description of its
      proteins-targets allows to analyze repair potential and manifestation of
      premature ageing markers both in the cells obtained from AT patients and in the
      cells of their heterozygous parents. Primary skin fibroblasts obtained from AT
      patients and their heterozygous parents were analyzed by the flow cytometry and
      comet assay. It has been shown that cells of the patient AT8SP do not initiate
      cell cycle blockade after ionizing irradiation during all the experiment, unlike
      the healthy donor cells where cell cycle blockade is observed. Irradiated cells
      of the heterozygous parents demonstrated less brightly expressed changes in cell
      cycle parameters than healthy donor's cells did. The ability to repair DNA double
      strand breaks (DSBs) after irradiation is reduced in the cells of AT patients and
      their heterozygous parents in comparison with the healthy donor's cells. Cells of
      the healthy donor were capable to repair not less than 90 % of DNA damage for 2.5
      h. The repair efficiency in the cells of AT patients came only to about 30 % of
      DNA damage and in the cells of heterozygous carries of the disease was
      approximately 50 %. The difference in the dynamics of DNA damage repair process
      in different proband's families is in accordance with the reports about great
      phenotypic variety of the given disease.

PMID- 20141034
TI  - [Ultrastructural study of spermatogenesis in silversides Oncorhynchus kisutch and
      cherry salmon O. masou (Salmonidae, Teleostei)].
AB  - Spermatogenesis in the silversides Oncorhynchus kisutch and cherry salmon O.
      masou, was investigated by transmission electron microscopy. It has been shown
      that male germ cells of both species had no difference in dimensional and
      ultrastructural parameters. The characteristic feature of spermatogonia was the
      presence of germ determinant substance, a cytoplasmic barker of sex line cells.
      Primary and secondary spermatocytes, as well as early spermatids were arranged in
      clusters consisted of synchronously developing cells. The spermiogenesis was
      peculiar in arising of electron-lucent vesicle which formed a structural complex
      with apical dense part of nuclear envelope. This complex has clear similarity
      with unformed spermatid acrosomes in many Metazoa and has been termed by the
      authors as an acrosome-like structure (AS). Disappearance of AS occurring at the
      final stage of the spermiogenesis allows considering AS as a temporary existing
      structure recapitulating the ancestral morphotype of salmonid sperm. Spermatozoa
      of both species are typical acrosome lacking cells which are characteristic of
      many representatives of Teleostei having external fertilization.

PMID- 20141035
TI  - [The influence of dopamine on the ultrastructure of BHK-21 cells].
AB  - The influence of dopamine on the haloperidol of BHK-21 cells being in suspension
      or attached to substrate was investigated. It was shown that the ultrastructural
      changes affected mainly the cellular loci enriched by the cytoskeleton actin such
      as intercellular desmosome-like contacts, microvilli and cortical layer or mesh
      just beneath the plasmatic membrane. The desmosome-like contacts were
      hypertrophied, their electron density was increased and fibrilar bridges appeared
      in specialized contacts. Many microvilli fused with each other and with plasma
      membrane of the neighboring cells, or, on the contrary, split up. Frequently, the
      membrane surface between microvilli and particularly their apical parts was seen
      to be pierced by thin thread, morphologically similar to actin filaments. The
      cytoplasmatic matrix onto ultrathin sections had blotched appearance and at the
      ultrastructural level was represented by numerous randomly oriented actin
      filaments. The effect of dopamine was more pronounced in the BHK-21 cells when
      being in suspension than in attached to the substrate ones, which presumably
      occurred due to known lesser differentiation of the cytoskeleton in the formers.
      Finally, it was established that the preliminary blockade of cellular D2
      receptors with haloperidol neither affected the ultrastructure of BHK-21 cells
      nor prevented the following effect of dopamine. The data obtained suggest the
      direct interactions of dopamine with the actin cytoskeleton.

PMID- 20141036
TI  - [The role of ZF5 and CGGBP-20 transcription factors in expression regulation of
      human FMR1 gene responsible for X-fragile syndrome].
AB  - The human FMR1 gene encodes an RNA-binding protein taking part in translation
      regulation. The 5'-untranslated region of FMR1 gene contains a large number of
      tandem repeats of GCC triplets (5-50) which increasing (more then 200) is
      responsible for X-fragile syndrome (human congenital anomaly). As it has been
      shown earlier, al least two transcription factors (ZF5 and CGGBP-20) are capable
      of interacting specifically with GCC-repeats in regulatory regions of some genes.
      In this work, their roles in FMR1 gene expression regulation were studied. It was
      demonstrated by electrophoretic mobility shift assay that ZF5 recombinant protein
      specifically bound with GCC-triplet repeats (GCC9). Tissue-specific distributions
      of ZF5 and FMR1 proteins are very overlapped in mammalian. Inhibition of ZF5
      expression in HepG2 cells (by RNA interference) leads to at least 1.5 times
      stimulations of FMR1 gene expression in these cells. To estimate the contribution
      of GCC-triplet repeats in FMR1 gene expression regulation we used two alternative
      variants of genetic construction: containing luciferase reporter gene under 5'
      regulatory region fragment devoid of GCC-triplet repeats or including the GCC9
      nucleotide sequence. HepG2 cells were co-transfected by these constructions and
      expressions vectors of ZF5 or (and) CGGBP-20 respectively. It was found that ZF5
      downregulated the activity of 5'-regulatory region of FMR1 gene in both cases
      (acting probably through canonic 5'-GCGCGC3' sites). The presence of GCC-triplet
      repeats in the construction weakens this ZF5 effect. CGGBP-20 downregulates the
      activity of 5'-region of FMR1 gene in the presence of GCC-triplets only. The data
      obtained evidently indicate differently directed ZF5 effects on FMR1 gene
      expression and suggest the mechanism to explain the earlier demonstrated
      phenomenon about increasing of mRNA level in permutation FMR1 allele carries.

PMID- 20141037
TI  - [Inhibition of the adenylyl cyclase signaling system by colchicine and
      vinblastine in ciliate Dileptus anser].
AB  - Cytoskeleton plays a key role in functioning of hormonal signaling systems in
      vertebrate animals. The data on the influence of cytoskeleton components, in
      particular the microtubules, on functional activity of chemosignaling systems of
      unicellular organisms are absent at the present time. The aim of this work was
      the study of influence of microtubule-disrupting agents, colchicine and
      vinblastine, on the adenylyl cyclase (AC) system of free-living ciliate Dileptus
      anser. The treatment of D. anser with colchicine and vinblastine (10(-5)-10(-6)
      M) weakly influenced basal activity of AC, but caused essential decrease or
      complete blocking of AC stimulation by non-hormonal (GppNHp, sodium fluoride) and
      hormonal (aldrenaline, serotonin, glucagon) agents. As a result of this
      treatment, a decrease of the basal level of GTP-binding of heterotrimeric G
      proteins and inhibition of G-protein stumulation by the hormones were found. In
      the case of adrenaline it was that colchicine and vinblastine disturb the AC
      stimulation by the hormone, mediated with the G(s)-protein, but weakly influence
      its inhibitory AC effect, realized via the G(i)-protein. Thus, it was established
      for the first time that microtubules in unicellular organisms such as the ciliate
      D. anser are involved in regulation of functional activity of AC system, and
      their action is realized at the level of the G-proteins similar to the G(s)
      proteins of the vertebrates.

PMID- 20141038
TI  - [Heat shock proteins of 70 kDa family in the cells of free living and amphizoic
      amoeboid organisms].
AB  - The content of constitutive from of 70 kDa family heat shock pritein (Hsp70) was
      determined by the method of immunoblotting. 9 strains of representatives of the
      genus Acanthamoeba including 8 amphizoic (facultative parasitic) strains and one
      free-living (isolated from upper horizons of Arctic soils) were studied. We also
      examined 15 strains of free-living freshwater amoebae of various geographic
      origin, age and species. 14 of them belonging to the genus Amoeba and one to the
      genus Trichamoeba. The presence of Hsp70 was demonstrated in the cells of all 25
      freshwater amoeba strains, whereas it was shown only for 2 of amphizoic
      acanthamoebae strains. In all these cases, the position of zone at the blot,
      revealed by monoclonal anti-HSP70 antibodies, corresponded to polypeptide with
      molecular mass about 70 kDa. We also found rather high level of constitutive
      Hsp70 in the cells of contemporary free-living tundra soil representative.
      However, in this case, the stained zone occupied the position corresponding to MW
      about 60 kDa which was just the same as earlier obtained for the ancient tundra
      acanthamoebae strain from permafrost.

PMID- 20141039
TI  - [Application of Schiff's reagents with various spectral characteristics to
      determine the content of labile and stable glycogen fractions in isolated
      hepatocytes].
AB  - The dynamics of the total glycogen accumulation, its labile and stable fraction
      contents were studied in hepatocytes after administration of 30 % glucose to rats
      that had been starving for 48 h. In the study, the original method based on the
      use of Schiffs reagents with various spectral characteristics (auramine-SO2 - Au
      SO2 - and ethidium bromide-SO2 - EtBr-SO2) was applied allowing detection and
      quantitative determination of the labile and stable glycogen fractions in the
      same hepatocytes to be achieved. Staining of the preparation by Au-SO2 during 40
      min revealed the labile glycogen fraction (green fluorescence, lambda(max) = 526
      nm). The following staining of the same sample by EtBr-SO2 during 50 min revealed
      stable glycogen fractions (red fluorescence, lambda(max) = 620 nm) in the cells.
      The measurement of fluorescence intensity in the corresponding spectrum permits
      the quantity of each glycogen fractions in isolated liver cells to be determined.
      It has been shown that as the glycogen accumulates in the hepatocytes its labile
      fraction content increases. The correlation coefficient (r) between the labile
      fraction content and the total glycogen content in hepatocytes obtained from the
      liver of starving rats was 0.95, and in hepatocytes isolated 20 and 30 min after
      the beginning of glucose refeeding to starving rats it was 0.95 and 0.98,
      respectively. 90 and 120 min after administration of glucose to starving rats,
      when the hepatocyte population becomes non-synchronous with respect to synthesis
      and degradation of glycogen in cells, the dependence of the labile fraction
      content upon the quantity of the total glycogen becomes less expressed (r= 0.71
      and 0.82, respectively). Thus the application of Schiff's reagents with various
      spectral characteristics enables us to obtain valuable information about glycogen
      structure in cells and about the processes of its synthesis and degradation in
      the cell population.

PMID- 20141040
TI  - [Beta-endorphin as the endogenous regulator of immune processes].
AB  - Endogenous opioid peptides represent the group of bioregulatory factors
      possessing a wide range of biologically active effects. One of most essential
      functions of endogenous opioids appears to be the realization of cellular
      interaction between nervous and immune systems. Beta-endorphin is a peptide
      hormone that is the most active and multi-functional representative of the opioid
      peptide family. This review summarizes current observations on the nature ofbeta
      endorphin, its production by the immune system cells, opiate receptor structure
      and expression, as well as the peptide effect on the processes of cellular
      activation, proliferation, and differentiation in innate and adaptive immunity.

PMID- 20141041
TI  - A tribute to Elena Korneva: reversal of aging and cancer by Pavolvian
      conditioning: neuroimmunmodulation--some history.

PMID- 20141042
TI  - [Response of hypothalamic orexin-containing neurons to stimuli of antigen and non
      antigen nature].
AB  - Orexin is a hypothalamic peptide, a neurotransmitter described in 1998.
      Orexinergic neurons are localized in hypothalamic structures and play a
      significant role in regulation of various physiological functions. The
      localization oforexin-containing neurons and their projections in hypothalamus of
      Wistar rats and other structures of CNS are presented. The participation of
      orexinergic neurons in the regulation of feeding behavior and in the sleep/wake
      cycle as well as their involvement in the regulation of immune functions is
      discussed. There are experimental data, containing comparative analysis oforexin
      containing neurons responses to stimuli of antigenic and non-antigenic nature,
      which suggest functional heterogeneity of orexin-containing neurons of
      hypothalamus that leads, particularly, to involvement of different neurons in the
      realization of brain reaction to antigen and non-antigen stimuli. Both analyses
      ofpreproorexin gene expression level and morphofunctional characteristics of
      orecxin-containing neurons of hypothalamus after antigen challenge suggest the
      possibility of their participation in the mechanisms of realization of brain
      reaction to antigen challenge.

PMID- 20141043
TI  - [Cellular and molecular mechanisms of interaction between the neuroendocrine and
      immune systems under chronic fatigue syndrome in experiment].
AB  - One of the main mechanisms of chronic fatigue syndrome development involves
      disturbances of interaction between the immune and neuroendocrine systems. The
      adequate experimental model for the search of these mechanisms is induction of
      fatigue in animals via the single intraperitoneal administration of synthetic
      double-stranded RNA - Poly I : C. Investigation of alterations in cytotoxic and
      proliferation activities of splenocytcs, the intensity of immunomodulatory
      cytokines signaling via the sphingomyelin pathways in membrane P2 fraction of the
      brain cortex, as well as the activity of hypothalamic-pituitary adrenal (HP A)
      axis in the dynamics of chronic fatigue syndrome in rats has performed.
      Inhibition of both cytotoxic and proliferative activities of splenocytes during
      the period of fatigue development has been shown. Priority data concerning the
      suppression of the activity of neutral sphingomyelinase (nSMase) - the key enzyme
      of the sphingomyelin cascade - in membranes ofthe cells from the brain cortex on
      the 3d day after Poly I : C administration to rats have been obtained. It was
      found that Poly I : C injection to rats led to disturbed HPA axis functions which
      was manifested by decreased corticosterone concentration in standard functional
      assays with ACTH and hydrocortisone administration. It is suggested that
      disturbances in interaction between the immune and neuroendocrine systems during
      development of chronic fatigue syndrome, including alterations in HPA axis
      activity, are realized both on the level of changes in the activity of immune
      competent cells and immediately on membranes of the brain cells.

PMID- 20141044
TI  - [Comparative analysis of orexin-containing neurons reactions in the rat
      hypothalamus after lipopolysaccharide injection in different doses].
AB  - Nowadays many investigations are focused on the participation of orexin
      containing neurons in CNS reactions caused by antigen injection, for instance
      lipopolysaccharide (LPS). The analysis of orexin-containing neuron: quantity in
      2, 4 and 6 hours after injection of low non-septic dose of LPS in comparison with
      a higher subseptic dose, was carried on. The increase of the orexin-immunoractive
      neurons quantity was observed in 2 and 4 hours after administration of 25 meg/kg
      of LPS, whereas in 6 hours the decrease of it was demonstrated. Injection of
      higher dose of LPS (500 meg/kg) was shown to cause the more significant decrease
      of the quantity of orexin-positive neurons only in 6 hours after antigen
      administration. The obtained data evidence the alteration of orexin content
      detected in neurons somas and the shift of the balance of its synthesis and
      utilization processes in response to the LPS injection.

PMID- 20141045
TI  - [Immunereactivity of hypothalamic orexin-containing neurons after restraint and
      cold stress in rats].
AB  - Studying of immunereactivity of orexin-containing neurons after restraint and
      cold stress has allowed to reveal a selective change of a degree
      ofimmunereactivity ofhypothalamic orexin-containing neurons. Orexin-containing
      neurons are located in structures 28, 29, 31 levels of brain slices and have the
      different degree of immunereactivity that indicates functional heterogeneity of a
      population of hypothalamic orexin-containing neurons. Structures and zones of
      hypothalamus involved in development of complex brain responses to restraint or
      cold stress applications were identified. Changes of immunereactivity of orexin
      containing neurons located in the areas involved in system of regulation
      ofthermogenesis (DMH, PH and some zones LHA) suggest a possibility of orexin
      containing neurons participation in thermoregulation.

PMID- 20141046
TI  - [Functional activity of bone marrow-derived peptides (myelopeptides)].
AB  - The review describes structure and functions of bone marrow-derived peptides
      (myelopeptides). The final biological effects of these endogenous bioregulators
      (antitumor, antiviral, anti-infectious, antileukemia etc.) are due to their
      immunocorrecting and differentiating activity. Myelopeptides are the integral
      parts of the immune homeostasis maintenance system. Nowadays, medical
      preparations with no side effects and natural mechanisms of action are being
      developed on the basis of synthesized myelopeptides.

PMID- 20141047
TI  - Prandial increases of leptin and orexin in the brain modulate spatial learning
      and memory.
AB  - Leptin is well known to be involved in the inhibition of feeding, hermogenesis,
      reproduction and neuroendocrine functions through its actions on the rodents
      hypothalamic receptors. Leptin facilitated the presynaptic transmitter release
      and postsynaptic sensitivity to the transmitters in the hippocampal CA1 neurons.
      Thus long-term potentiation (LTP) and the phosphorylation of Ca2+/calmodulin
      protein kinase II (CaMK II) were facilitated in the CA1 neurons. Therefore
      behavioral performance related to spatial learning and memory was improved by
      leptin in vivo applications. Orexin-A produced by glucose-sensitive neurons in
      the lateral hypothalamic area (LHA) and released during food intake facilitates
      feeding. Orexin-A suppressed LTP and CaMK II phosphorylation without affecting
      the presynaptic transmitter release. Therefore behavioral performance on learning
      and memory was impaired. The present studies suggest that leptin and orexin
      signalings in the brain may have important implications for cognitive function.

PMID- 20141048
TI  - The role of immune cells in brain metastasis of lung cancer cells and neuron
      tumor cell interaction.
AB  - Following any type of brain injury such as lesion, stroke, and tumor/cancer
      invasion, microglia are rapidly activated and recruited to the site of injury.
      Microglia is the main immune effector cell population of the central nervous
      system and control immune cell recruitment. However, the molecular mechanism of
      brain metastasis and interaction between neuron-glia-tumor cells are poorly
      understood. Therefore, we established an animal model for brain metastasis using
      human lung cancer-derived cells (HARA-B) in nude mice. Accumulation of activated
      microglia was observed around tumor cells depending on the size of metastatic
      foci and the area of the brain. In vitro study, conditioned medium from primary
      cultured mouse microglia inhibited the proliferation of tumor cells, while tumor
      cell-conditioned medium inhibited the proliferation of primary cultured neurons
      from mouse cortex. Though the responsible factors released from microglia and
      tumor cells are still under investigation, these studies will contribute to
      understand the mechanism of cell-cell interaction in the brain and possible
      therapeutic target for brain metastasis.

PMID- 20141049
TI  - [Dose-dependent effects of neuroimmunomodulator interferon alpha on behavior of
      humans and animals].
AB  - The review analyses the literature on polyfunctional activity of the cytokine
      interferon-alpha (IA) which has neuroimmunomodulatory properties and is used for
      treatment of viral and oncologic diseases. The major intention is devoted to
      action of small and high doses of IA on different forms of animals and human
      behavior. We suggest that chronic treatment with small IA doses is more effective
      than high dose therapy.

PMID- 20141050
TI  - [Activity of calpaines in spinal cord cells of the rats with experimental
      allergic encephalomyelitis of different grades].
AB  - In simulation of experimental allergic encephalomyelitis (EAE), a hyperactivation
      of calpaines occurs due to m-calpaines. The m-calpaines involvement in the
      process of initiation of neurons and glial cells death in the EAE development was
      suggested.

PMID- 20141052
TI  - [On the second international symposium "The interaction of nervous and immune
      systems under normal and pathological conditions"].

PMID- 20141051
TI  - [In search of the guilty: analysis of encephalitogenic T cell migration pathways
      on preclinical phase of EAE after their intravenous or intraperitoneal
      injection].
AB  - Adaptive-transfer experimental autoimmune encephalomyelitis is an inflammatory
      neurodegenerative disease which is induced by injection of activated
      encephalitogenic T cells. Adaptive-transfer experimental autoimmune
      encephalomyelitis is a major experimental tool for investigation ofT cell
      function in multiple sclerosis development. Activated myelin basic protein
      specific T cells are able to invade and inflame the central nervous system which
      is followed by axonal injury and paralysis on the third day after injection. In
      the prodromal phase of EAE encephalitic T cells migrate through different organs
      which alter their phenotype before invading the CNS. We compared migratory
      patterns of encephalitic T cells after intravenous and intraperitoneal injection
      to elucidate which organs may play an important role in the formation of
      "migratory" phenotype. We found that encephalitogenic T cells ultimately migrate
      through spleen and parathymic lymph nodes regardless of the start point of cells
      migration after i.p. and i.v. injection. We hypothesise that cellular and
      extracellular components of these organs could be involved in the formation of T
      cells "migratory" phenotype which is necessary for penetration via blood-brain
      barrier.

PMID- 20141053
TI  - [Influence of the treatment of the atrioventricular reentry tachycardia by RF
      catheter ablation on the left ventricular systolic and diastolic function and
      exercise capacity].
AB  - INTRODUCTION: The purpose of the present study was to evaluate the effects of RF
      ablation on parameters of left ventricular (LV) function and exercise capacity in
      patients with AVRT. MATERIAL AND METHODS: The study population consisted of 24
      subjects (10M, 14F), mean age 38.1+/-8.9 years. Subjects over 50 years of age,
      with concomitant cardiovascular disease and EF<50% were excluded from the study.
      The following examinations were performed in all patients at baseline and at six
      months after the procedure: 1) physical examination, 2) standard ECG recording,
      3) 24hr Holter monitoring, 4) transthoracic ECHO, 5) treadmill exercise test
      using the modified Bruce protocol to evaluate exercise duration, peak heart rate
      and workload achieved. RESULTS: After RF ablation NYHA functional class improved
      in the whole population. The left ventricular dimensions (LVESD, LVEDD), left
      ventricular ejection fraction (LVEF), fractional shortening (FS) in AVRT group
      remained unchanged. Parameters of LV diastolic function significantly improved,
      whereas systolic pulmonary venous flow S and pulmonary venous atrial reversal
      flow AR were significantly reduced (p<0.005, p<0.001, respectively). All
      dimensions of the left atrium significantly decreased after the procedure
      (p<0.001). In all patients parameters of exercise capacity were increased after
      the procedure. CONCLUSIONS: In patients with AVRT RF ablation did not affect
      significantly left ventricular dimensions and systolic function. Elimination of
      AVRT resulted in improved NYHA functionalclass, diastolic LV function, exercise
      capacity and reduction of left atrial size.

PMID- 20141054
TI  - The influence of low-frequency magnetic field on plasma antioxidant capacity and
      heart rate.
AB  - INTRODUCTION: Low-frequency magnetic field is widely applied as magnetotherapy in
      physiotherapeutic treatment. Recognition of positive and negative effects of the
      magnetic field has been the subject of numerous studies. Experimental studies
      concern, among others, the effect of this field on the heart rate and plasma
      antioxidant capacity. The aim of the study was to check whether a time-variable
      magnetic field of constant frequency and induction affects the heart rate and
      plasma antioxidant capacity. MATERIAL AND METHODS: The tests were performed on
      Spraque-Dawley rats exposed to the magnetic field of the following parameters:
      frequency - 40 Hz, induction - 7 mT, time of exposure - 30 and 60 minutes. The
      measurements of ECG and plasma antioxidant capacity expressed in the number of
      reduced iron ions were performed on experimental animals: before, after a single
      exposure and after 14 days of exposure. RESULTS: A significant decrease of the
      heart rate was observed after 14 days of exposure. A variable magnetic field of
      the parameters: frequency - 40 Hz, induction - 7 mT and exposure time of 14 days
      caused an increase of the organism antioxidant defence, whereas a variable
      magnetic field of the frequency of 40 Hz, induction - 7 mT and exposure time 60
      minutes for 14 days caused a significant decrease of the organism antioxidant
      defence. CONCLUSIONS: The exposure time affects heart rate, plasma antioxidant
      capacity and the organism defense ability against free radicals.

PMID- 20141055
TI  - [Activity of GSH-dependent enzymes in blood serum of patients with acute and
      chronic pancreatitis].
AB  - INTRODUCTION: Since one of the many proposed factors in the pathogenesis of acute
      and chronic pancreatitis is oxidative stress, the aim of the research was
      evaluation of antioxidant defense mechanisms, with particular emphasis on the
      role of reduced glutathione and GSH-dependent enzymes. MATERIAL AND METHODS: The
      study involved a group of 35 patients with pancreatitis treated at the Clinic of
      General Surgery and Transplantation Medical University of Warsaw in the period
      from 2005 to 2007. This group consisted of 20 patients with mild symptoms (edema)
      of the form of acute pancreatitis and 15 patients with chronic pancreatitis,
      short duration of the disease. In all patients with acute and chronic
      pancreatitis qualified for the study were measured in serum markers of oxidative
      stress: concentrations of reactive thiobarbituric acid (TBARS), which determines
      the level of lipid peroxidation and reduced levels of glutathione (GSH) and
      activity of antioxidant enzymes: total glutathione peroxidase (cal. GSHPx),
      glutathione S-transferase (GST) and glutathione reductase (GSHR). RESULTS: We
      found increased lipid peroxidation level, decreased level of GSH, and changes in
      activity of GSH-dependent enzymes in blood serum of patients with acute and
      chronic pancreatitis, compared to blood serum from healthy persons. CONCLUSIONS:
      Obtained results indicate participation of oxidative stress in pathogenesis of
      those diseases, and systemic impairment of antioxidative mechanisms.

PMID- 20141056
TI  - [Application of long term subcutaneously implanted access into the central veins
      system of "PORT" type in the Clinic of Pediatry, Pediatric Hematology and
      Oncology in Zabrze--15 year own observations].
AB  - INTRODUCTION: Long term disease treatment in children is a very special medical
      problem due to a necessity of maintaining an efficient venous access for many
      months and even years. Vascular ports applied in those children improved the
      conditions of treatment and a quality of life, additionally, made the job of
      personnel taking care of them easier. MATERIAL AND METHODS: The study presents
      own experience in long-term venous access into the central veins system, so
      called vascular ports, gathered for 15 years of using them in children with
      hemato-oncogical diseases. The analysis of 309 of implanted vascular ports was
      done taking into consideration the maintenance and complications. Ports were
      implanted in 300 children with oncological diseases. The received results are
      presented in numbers and percentage. RESULTS: Mean time of port insertion has
      decreased in comparison to earlier studies by 35 days and now is 722 days, median
      658 days, however, minimal and maximal time of port insertion has changed
      respectively 7 and 2099 days. The total time of port insertion in this period was
      232 536 days. The observation showed 31 (10.03%) cases of complications, out of
      which the most common were set infection (16 - 5.18%), catheter occlusion by a
      clot (7 - 2.27%) and "spontaneous" catheter move out of vessel lumen (3 - 0.97%),
      migration of a torn-off catheter into the right heart ventricle (2 - 0.65%).
      CONCLUSIONS: 1. Application of vascular ports enabled a long-term and intensive
      chemotherapy in children with oncological and hematological diseases. 2.
      Application of vascular ports bears a minor risk of complications, the most
      dangerous observed complication was a replacement of a torn-off catheter into the
      right heart ventricle.

PMID- 20141057
TI  - [Evaluation of frequency of fatigue syndrome in patients with multiple
      sclerosis].
AB  - INTRODUCTION: Fatigue is a common symptom occuring in different neurological
      diseases. It has an influence on social and proffesional live, and daily living
      activities of the patients. The aim of the study was to assess frequency of
      fatigue and its association with depression and anxiety in patients with multiple
      sclerosis (MS). MATERIAL AND METHODS: The examined group consisted of 44 patients
      with MS (mean age: 36.3+/-9.4 years). The control group involved 30 healthy
      volunteers. All the subjects fulfilled two questionnaires: Fatigue Severity Scale
      and Hospital Anxiety and Depression Scale. RESULTS: Fatigue was present in 29 MS
      patients (66%) and in 8 controls (26.7%) (p=0.0002). Anxiety was noticed in 11 MS
      patients (25%) and in 2 controls (6.7%) (p=0.002). Depression was diagnosed in 3
      MS patients (6.8%) and 2 controls (6.7%) (NS). Frequency of fatigue was similar
      in women and men, but anxiety and depression were more common in women. There was
      no correlation between fatigue and age, duration of the disease and EDSS. An
      association between fatigue and depression, but not anxiety, was observed.
      CONCLUSIONS: Fatigue is a very common symptom in MS, sometimes associated with
      depression. It should be considered in every patient with MS, independently from
      age, sex, disability and duration of the disease.

PMID- 20141058
TI  - The image of one's own body and the effectiveness of weight loss therapy.
AB  - INTRODUCTION: Aim of this study was to check the relation between body image and
      the effectiveness of weight loss therapy. MATERIAL AND METHODS: Four body image
      aspects were separated: a declarative, a sensory, an imaginable and a perceived
      one. Five research methods were used: an objective body weight measurement, the
      silhouette test, the body mass assessment scale, the body satisfaction scale and
      a questionnaire. All methods were used: at the beginning of the therapy, after 5
      per cent, 10 per cent and 15 per cent reduction in initial body weight. SUBJECTS:
      150 overweight women, participants of an outpatient weight loss therapy. RESULTS:
      The biggest body weight reduction was linked with: an earlier appearance of
      excess weight (Z=-2.281, P<0.05), bigger planned body mass reduction (Z=-2.472,
      P<0.05), more overweight declarative self-estimation (Z=-2.136, P<0.05), worse
      declarative sense of looking nice (Z=-2.126, P<0.05), rare confirmation that once
      they had looked as an imaginary Self (Z=-1.990, P<0.05), greater general
      satisfaction with the appearance of their imaginary Self (Z=-2.357, P<0.05),
      frequent statement that an imaginary Self is attractive (Z=-2.060, P<0.05) and
      agile (Z=-2.387, P<0.05),worse perceived looking nice (Z=-2.596, P<0.01). A 15%
      (R2=0.148) reduction in initial body weight was explained with initial values of
      the position in the silhouette test in a perceptive (Beta=0.256, P<0.01) and an
      imaginable (Beta=-0.256, P<0.001) body image aspect and the BMI of an imaginary
      Self (Beta=0.318, P<0.01). CONCLUSIONS: The effectiveness of weight loss therapy
      is supported by describing and seeing oneself as an obese person as well as
      imagining oneself as slim but characterized by high body mass index.

PMID- 20141059
TI  - [Obstruction of jejunum due to adenocarcinoma].
AB  - The paper presents a rare case of jejunum adenocarcinoma at a 66-year old female.
      The patient was admitted to the hospital due to not characteristic abdominal pain
      and periodical nausea and vomitting lasting few months. After realized laboratory
      investigation, especially on the basis of contrast, radiological procedure of the
      gastrointestinal tract, the high obstruction was detected. Then the patient has
      been operated on. Postoperative period proceeded without complications. Eleven
      monthly observation after the operation showed no recurrence of cancer. The
      presented case confirms vole of contrast radiological procedure of the
      gastrointestinal tract, which is simple and generaly available examination, in
      the diagnosis of bowel obstruction. The correct interpretation of the result was
      an indication of surgical intervention. However the final diagnose is established
      on the base of postoperative histopatological examination.

PMID- 20141060
TI  - [Pancytopenia after methotrexate treatment].
AB  - The use of methotrexate is associated with the risk of numerous, sometimes life
      threatening, side effects. We describe a 76-year-old female patient treated with
      methotrexate (MTX) due to vertebral joint disease of unknown etiology. During the
      outpatient therapy, which was not conformed to doctor's recommendations, acute
      liver failure and symptoms of bone marrow damage developed. Despite intensive
      hospital treatment, the patient died.

PMID- 20141061
TI  - [Clostridium spp. spores in pathomechanism of autism].
AB  - Autism is a syndrom with unknown etiology, however many hypothesis are described
      in medical publications. These hypothesis include clostridial spores as key
      elements. Exo- and also endogenous spores are possible cause of autism:
      antibiotics have lack of effects on spores, which germinate after discontinuation
      of antibiotic therapy to vegetative neurotoxin producing forms. In this paper we
      discuss possible role of gastrointestinal tract and intestinal microflora in
      pathomechanism of autism on the light of recent publications.

PMID- 20141062
TI  - [Sudden infant death syndrome--current opinions on etiology and pathogenesis].
AB  - Sudden infant death syndrome (SIDS) remains still unsolved medical entity. At
      present about 80 theories and hypotheses concerning SIDS exist. The authors
      describe current opinions concerning SIDS pathogenesis and etiology.

PMID- 20141063
TI  - [Health-related quality of life in women with endometriosis].
AB  - According to definition, endometriosis is a chronic gynaecological disease which
      results from ectopic location of the endometrium outside the uterine cavity. On
      the basis of various researches it is estimated that prevalence of endometriosis
      in the general population is 10% and the disease concerns women mainly in
      reproductive age. As an effect of the disease, following common gynaecological
      and psychiatric symptoms appear: chronic pelvic pain which occurs in different
      circumstances, depressive and anxiety disturbances. In relation to pathological
      changes, decrease of health-related quality of life (QOL) is observed. The topic
      of medical researches concerns frequently an influence of pharmacological and
      surgical treatment on QOL improvement in women with endometriosis. To achieve
      objective results in evaluation of quality of life, it is recommended to use
      standardized and validated questionnaires, such as EHP-30, EHP-5, SF-36, WHOQOF
      100 or WHOQOL-BREF.

PMID- 20141064
TI  - [Erectile dysfunction in patients treated for bladder and prostate cancer].
AB  - The disorders of the erectile dysfunction are well-known complication connected
      with the operating interventions of abdominal and pelvic surgery. Radical
      treatment of the malignancy, vascular operations and transurethral resection can
      lead to the rise of these disorders. The majority of these interventions is
      carried out at patients in the old age at which the disorders of the erection
      already existed about the various degree of intensification before treating
      operating how also the presence of the illnesses of the leaders to their rise or
      intensification after finishing the treatment (diabetes, arterial hypertension,
      arteriosclerosis). Patients in the young aged wait not only curing from the
      malignancy from second side, but also the behaviour of the quality of the life
      (QOL - quality of life), which the correct erection enabling is one of elements
      satisfying living together.

PMID- 20141065
TI  - [The rules of ethics, legal aspects, and the issue of euthanasia].
AB  - The issue of euthanasia is gaining greater momentum in Poland. It is a matter of
      fact that Poland is a country with an increasing aging population. As a result of
      this increased awareness, this topic is also becoming increasingly controversial.
      Does a doctor have the right to decide, on behalf of another person, if they
      should end their life? What limitations should doctors be bound by in terms of
      their legal and ethical obligations? The purpose of this study is to investigate
      the ethical and legal implications associated with euthanasia.

PMID- 20141066
TI  - Fibrolamellar hepatocellular carcinoma at a tertiary centre in South Africa: a
      case series.
AB  - BACKGROUND: Fibrolamellar carcinoma (FLC) is an uncommon malignant tumour of
      hepatocyte origin that differs from hepatocellular carcinoma (HCC) in aetiology,
      demographics, condition of the affected liver, and tumour markers. Controversy
      exists whether FLC demonstrates a more favourable prognosis than typical HCC. A
      review of existing literature reveals a dearth of FLC data from the African
      continent. METHODS: We utilised the prospective liver resection database at
      Groote Schuur Hospital to identify all patients who underwent surgery for FLC
      between 1990 and 2008. RESULTS: Seven patients (median age 21 years, range 19 -
      42, 5 men, 2 women) underwent surgery for FLC. No patient had underlying liver
      disease or an elevated alpha fetoprotein (AFP) at either initial presentation or
      recurrence. Six patients had a solitary tumour at diagnosis (mean largest
      diameter = 12cm), and underwent left hepatectomy (N=2), right hepatectomy (N=1),
      extended right hepatectomy (N=1), right hepatectomy (N=1), extended right
      hepatectomy (N=1), and segmentectomies (N=2). Three patients underwent a portal
      lymphadenectomy for regional lymphatic tumour involvement. One patient with
      advanced extrahepatic portal nodal metastasis was unresectable. No peri-operative
      deaths occurred. Recurrence occurred post resection in all 6 patients. Median
      overall survival was 60 months, and overall 5-year survival was 4 out of 7 (57%).
      Post-resection survival (N=6) was 61 months, with a 5-year survival rate of 4 out
      of 6 (67%). The patient with unresectable disease survived 38 months after tumour
      embolisation with Lipiodol. CONCLUSION: Our series suggests that despite (i) a
      high resection rate of solitary lesions with clear tumour resection margins, and
      (ii) absence of underlying liver disease, FLC has a high recurrence rate with an
      ultimately poor clinical outcome. These findings concur with recent international
      experience of FLC. experience of FLC.

PMID- 20141067
TI  - Long-term prospective randomised clinical and manometric comparison between
      surgical and chemical sphincterotomy for treatment of chronic anal fissure.
AB  - AIM: To compare surgical and chemical sphincterotomy for treatment of chronic
      anal fissure. METHODS: The 160 patients studied were randomly divided into four
      equal groups, treated by lateral internal sphincterotomy (group S), local
      diltiazem ointment (group D), local glyceryl trinitrate ointment (group GTN), or
      injection of botulinum toxin into the internal anal sphincter (group BT). Anal
      manometry was performed before and 3 months after treatment. Patients were
      followed up for 5 years. RESULTS: Complete pain relief was achieved in means (+/-
      standard deviation) of 5.7+/-7.8 days (group S), 15.7+/-5.9 days (group D),
      15.6+/-5.9 days (group GTN) and 2.7+/-3.6 days (group BT). The mean times to
      healing were 4.5+/-1.2 weeks (group 1), 5.1+/-1.1 weeks (group D), 5.0+/-1.1
      weeks (group GTN) and 5.1+/-1.3 weeks (group BT). Mean resting and squeeze anal
      pressures decreased significantly after sphincterotomy. Recurrence rates were 10%
      in group S, 65% in group D, 57.5% in group GTN and 52.5% in group BT. CONCLUSION:
      Lateral internal sphincterotomy is an easy procedure with satisfactory results,
      minimal complications and a low recurrence rate. Medical sphincterotomy is safe
      and easy, with mild complications. Its effect is reversible, and relapse is
      common. We recommend that medical sphincterotomy be tried before surgery or in
      patients who are unable or unwilling to undergo surgery.

PMID- 20141068
TI  - Tuberculous anal fistulas--prevalence and clinical features in an endemic area.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of
      tuberculosis (TB) in anal fistulas at a referral hospital in Cape Town, and to
      document the clinical features and course of patients with tuberculous anal
      fistulas. PATIENTS AND METHODS: This was a prospective study of all patients who
      underwent surgery for anal fistulas at the Colorectal Surgery Unit at Groote
      Schuur Hospital, Cape Town, from 2004 to 2006. Tissue was submitted for
      histopathological examination, Ziehl-Neelsen (ZN) staining and TB culture. The
      patients with proven TB were followed up until January 2008. RESULTS: During the
      3-year study period, 117 operations were performed on 96 patients. TB was
      diagnosed in 7 of the 96 patients (7.3%). In 5 of these 7 cases, the diagnosis of
      TB could be proven on histological examination and ZN staining, while in 2 cases
      the diagnosis could only be made on TB culture. None of the 7 patients had
      systemic features suggestive of TB, and only 1 had evidence of TB on a chest
      radiograph, Five patients were HIV-negative, and 2 declined testing. After a
      median follow-up of 2 years, 5 of 7 patients had evidence of recurrent or
      persistent fistulas, despite having completed 6 months of TB treatment.
      CONCLUSION: At a referral hospital in an endemic area, TB was present in 7.3% of
      anal fistulas. Histopathological examination including ZN staining was inadequate
      to make the diagnosis in a third of these patients. Tissue from anal fistulas
      should therefore routinely be sent for TB culture as well as histopathological
      examination and ZN staining in areas where TB is prevalent.

PMID- 20141069
TI  - An audit of the quality of care of traumatic brain injury at a busy regional
      hospital in South Africa.
AB  - Access to care by a dedicated neurosurgical unit is limited in the developing
      world, and the vast majority of patients who sustain a head injury are managed by
      general surgeons. Prevention of secondary brain injury is paramount. While the
      principles of management are relatively straightforward, delivering this care may
      be difficult. This audit looks at the spectrum of head injuries presenting to a
      busy regional hospital and attempts to measure the quality of care offered to
      these patients. PATIENTS AND METHODS: The audit includes three separate sections.
      The first is a prospective audit of all patients with a traumatic brain injury
      presenting to the Accident and Emergency (AE) department at Edendale Hospital,
      Pietermaritzburg, over a 2-month period. The next two sub-audits consist of a
      random review of referral letters and AE clerking notes to assess the quality of
      care received by these patients. A total of 25 referral letters and 28 AE
      inpatient notes were randomly chosen for review and compared with agreed
      standardised markers for quality of care. RESULTS: Over the 2 months October and
      November 2007, 150 patients with a head injury were seen in the AE department. Of
      these 117 were male. A total of 76 were discharged home after investigation with
      a head injury warning chart, 49 were admitted to the general wards, 11 were
      admitted to the surgical intensive care unit, 10 were referred to the
      neurosurgical centre in Durban, and 4 died in the AE department. Of the 10 who
      needed advanced neurosurgical care, 3 required urgent burr-holes before referral.
      One of these patients died. All the remaining 9 patients who were transferred to
      the neurosurgery unit survived. The referral letters and AE clerking notes
      revealed major deficits. CONCLUSION: Traumatic brain injury is a common problem.
      Only a small subset of patients require specialised neurosurgical care. Although
      many patients with intracranial injury can tolerate the delay associated with
      transfer, some cases are acute and urgent intervention by non-neurosurgeons is
      needed. Prevention of secondary brain injury is poorly understood and not
      prioritised. This situation needs to be improved. The introduction of formalised
      standard referral and management sheets may help to improve care.

PMID- 20141070
TI  - Situs inversus abdominalis and duodenal atresia: a case report and review of the
      literature.
AB  - Fewer than 20 patients born with situs inversus and duodenal atresia have been
      reported in the literature. We present a patient with this condition. A newborn
      baby presented shortly after birth with persistent bilious vomiting. An abdominal
      radiograph showed a right-sided stomach bubble and a second bubble on the left -
      typical of duodenal atresia but with mirror image configuration. Laparotomy
      confirmed the diagnosis of situs inversus abdominalis, which was also
      demonstrated by contrast studies and ultrasound. Duodenoduodenostomy was
      performed and the patient discharged on day 8 postoperatively. Situs inversus is
      associated with other congenital malformations including splenic malformations,
      left-sided liver and cardiac abnormalities; it is rarely associated with duodenal
      atresia. Duodenal obstruction in the presence of situs inversus has been
      described, including obstruction due to a web, stenosis, pre-duodenal portal vein
      and complete atresia. The patient presented in this paper had a duodenal web in
      the second part of the duodenum. Before undertaking surgery it is important to
      establish the presence of associated gastrointestinal and cardiac abnormalities.

PMID- 20141071
TI  - Osteopetrosis--a challenge for the orthopaedic surgeon.
AB  - Osteopetrosis (OP) is a rare heterogeneous group of inherited skeletal dysplasias
      characterised by osteoclast dysfunction, impaired bone resorption and poor bone
      remodelling. Three groups can be categorised on the basis of clinical findings.
      These include neurological symptoms, haematological abnormalities and renal
      tubular acidosis in the first group. Increased bone density, osteomyelitis and
      frequent fractures are the clinical findings in the second group, and the third
      group have normal life expectancy but may develop cranial nerve compression and
      osteomyelitis. Fractures in patients with OP are common and require appropriate
      pre-, peri- and postoperative management. The long bones are most frequently
      affected, fractures of the femoral neck and proximal (upper third) shaft being
      particularly common. This case report proposes possible operative fracture
      treatment in a patient with OP and highlights the potential perioperative
      pitfalls in this rare surgical population.

PMID- 20141072
TI  - In total oesophageal reconstruction, try, try and try again.

PMID- 20141073
TI  - [Prognosis of type A acute aortic dissection treated conservatively].
AB  - We examined 58 cases of type A acute aortic dissection treated from 2003 to 2005
      in our hospital. Thirty-three patients were treated surgically and 25 patients
      were treated conservatively. Among the 25 patients treated conservatively, 13
      patients had open false lumen, and were eligible for surgical therapy. Surgical
      therapy was abandoned however, for various reasons (stroke, advanced age,
      malignancy, renal disease, lung disease, or patient's reject). Thirteen patients
      (52%) treated conservatively died while only 1 patient (3%) treated surgically
      died. Patients with thrombosed false lumen had good prognosis while those with
      open false lumen or ischemic complication had poor prognosis. It is concluded
      that patients with thrombosed false lumen of type A acute aortic dissection could
      receive conservative therapy with surgical team's back up and close computed
      tomography (CT) follow up to detect recanalization and enlargement of the aorta.

PMID- 20141074
TI  - [Pleomorphic liposarcoma in anterior mediastium].
AB  - The patient was 70-year-old man. He had complained of general fatigue and
      hoarseness for 5 months. Chest computed tomography scan demonstrated a large
      anterior mediastinal tumor. The diagnosis of high grade malignant sarcoma was
      established with needle biopsy and the complete resection through median
      sternotomy was conducted. The tumor was histopathologically diagnosed pleomorphic
      liposarcoma. Six months after operation, right supraclavicular lymph node
      metastasis was noted. Radiotherapy was performed, but the liver metastasis
      appeared subsequently 16 months after operation. Pleomorphic type is considered
      one of the poorest prognostic liposarcoma and should be required special
      attention.

PMID- 20141075
TI  - [Severe coronary artery spasm immediately after aortic valve replacement].
AB  - We report a case of 72-year-old man with severe manifestations of coronary artery
      spasm immediately after aortic valve replacement (AVR), which was associated with
      hemodynamic and arrhythmic instability. The AVR was performed under mild
      hypothermic cardiopulmonary bypass (34 degrees C), and retrograde blood
      cardioplegia was intermittently delivered at the same temperature. Immediately
      after the operation, the patient suddenly developed severe bradycardia and
      hypotension, and repeated ventricular fibrillation. Percutaneous cardiopulmonary
      support system (PCPS) and intra-aortic balloon pumping (IABP) were required for
      this circulatory collapse. Echocardiography revealed left ventricular segmental
      dysfunction, and coronary artery bypass grafting (CABG) to the right coronary
      artery and the left ascending artery was performed [during CABG, coronary spasm
      was strongly suspected by repetitive ST elevation and depression on
      electrocardiogram (ECG) monitor]. Eventually, the spasm subsided with the
      intravenous infusion of nitrates, nicorandil, and diltiazem. The remaining
      postoperative course was uneventful and the patient was discharged on the 24th
      postoperative day in good clinical condition.

PMID- 20141076
TI  - [Simultaneous operation for Ebstein's anomaly and lung cancer].
AB  - The number of patients with coexisting cardiac disease and lung cancer have been
      increasing. The issue of performing simultaneous pulmonary resection and cardiac
      surgery remains controversial. We report a patient who underwent simultaneous
      surgery for Ebstein's anomaly and lung cancer with a good outcome. The tricuspid
      valve replacement with bioprothesis and the closure of a foramen ovale for
      Ebstein's anomaly was 1st performed under cardiopulmonary bypass. The resection
      of the right upper pulmonary lobe and mediastinal lymph nodes followed. The
      postoperative course was uneventful.

PMID- 20141077
TI  - [Experience of damage control as the primary surgery for thoraco-abdominal injury
      with hemorrhagic shock].
AB  - We experienced a traumatic victim with thoracic and abdominal injury with
      hemorrhagic shock, who was successfully treated with damage control. Thoracic
      drainage revealed more than 300 ml/hour of continuous hemorrhage in the left
      thoracic cavity with 60-80 mmHg of non-responding hypotention. Although we
      performed emergency partial resection of the injured lung, intraabdominal packing
      and transcatheter arterial embolization, intrathoracic hemorrhage and hemorrhagic
      shock was not controlled. We decided re-thoracotomy and performed peri-pulmonary
      packing around the injured lung, by which we successfully controlled temporary
      intrathoracic hemorrhage and definitive left lower lobectomy. Peri-pulmonary
      packing was effective for intrathoracic hemostasis without lethal ventilatory and
      circulatory complication in this case.

PMID- 20141078
TI  - [Pacemaker infection on the neonate with congenital heart disease].
AB  - A 6-day-old girl underwent pacemaker implantation for complete atrioventricular
      block through a subxiphoid incision. Epicardial leads were sutured on the right
      ventricle, and the pulse generator was buried in a subcutaneous pocket on the
      abdomen. After 3 days, the pacemaker site became infected. The whole pacing
      system was extracted immediately and replaced by temporary pacing leads. After
      the infection was controlled, a new pacemaker was implanted through a left
      thoracotomy during which an original Blalock-Taussig shunt was established. The
      new pulse generator was buried in a subcutaneous pocket in the left precordial
      area. The patient's postoperative course was uneventful, and there have been no
      signs of lead problems or re-infection. Using temporary pacing leads as a bridge
      to implant a new system and choosing a precordial subcutaneous pocket for the
      implantation site following suturing of the leads on the left ventricle through a
      left thoracotomy were useful in this case.

PMID- 20141079
TI  - [Chemotherapy with linezolid for chronic synthetic graft infection].
AB  - Infection of thoracic synthetic grafts is a serious problem, potentially leading
      to septicemia. Total removal of infected grafts might be too invasive for
      patients in poor general condition or who have long synthetic grafts. Effective
      and safe chemotherapy regimens are needed to control infection. A 75-year-old man
      with infected synthetic grafts of the ascending aorta, aortic arch, descending
      aorta, and thoracoabdominal aorta caused by methicillin-resistant Staphylococcus
      aureus was admitted to our hospital because of septicemia. He had previously
      received vancomycin for about 1 year at an outpatient clinic. The blood culture
      after admission was positive for vancomycin-intermediate Staphylococcus aureus.
      Linezolid was effective against septicemia, but caused side effects, such as
      blurred vision, severe diarrhea, and thrombocytopenia. Intermittent oral
      treatment with linezolid (1,200 mg/day) was then given for 7 days every 2 weeks.
      This treatment decreased the incidence of the side effects and had a beneficial
      effect on the infection.

PMID- 20141080
TI  - [Mycotic distal arch aneurysm successfully operated through L-incision approach].
AB  - A 70-year-old female who had undergone pancreato-duodenectomy 1 month before,
      presented with back pain. Computed tomography (CT) revealed a saccular aneurysm
      in the distal aortic arch (40 mm in diameter) and she was referred to our
      department. Despite proper antibiotic treatment, CT revealed progressive
      enlargement of the aneurysm and operation was performed. The aneurysm was treated
      by debridement of the infected aortic tissue and in situ replacement with a
      rifampicin-soaked vascular prosthesis through L-incision approach. After surgery,
      antibiotics were administrated intravenously for 1 month, followed by oral
      antibiotics. The patient is doing well 1 year after the operation.

PMID- 20141081
TI  - [Solitary metachnonous jejunum and duodenum metastasis after surgical resection
      of lung cancer].
AB  - We report a rare case of a 58-year-old man of long-term survival after surgical
      treatment of solitary metachnonous jejunum and duodenum metastasis from lung
      cancer. He underwent right upper lobectomy with a diagnosis of lung cancer which
      was histologically diagnosed as large cell carcinoma (pT4-MONO, stage IIIB). One
      month after the operation, he suffered from ileus caused by metastasis in the
      jejunum. Partial resection of the jejunum and postoperative chemotherapy were
      performed. Two years after the 2nd surgery, another metastatic tumor was found in
      the duodenum, and pancreatoduodenectomy was performed. The postoperative course
      of the patient was uneventful without recurrence 6 years after surgical resection
      of lung cancer.

PMID- 20141082
TI  - [Syndrome of inappropriate secretion of antidiuretic hormone associated with
      resection of pulmonary squamous cell carcinoma].
AB  - Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) shows various
      symptoms based on hyponatremia and brings catastrophic outcome occasionally. A 75
      years-old man was found to have an abnormal shadow of the right lung on chest X
      ray. Bronchoscopic examination showed that the abnormal shadow was aterectasis
      caused by the squamous cell carcinoma of middle lobe bronchus, and middle and
      lower lobectomy of the right lung was performed. On the postoperative day 2,
      suddenly the serum sodium concentration decreased to 116 mEq/l and serum
      osmolarity also decreased to 246 mOsm/l. Inspite of hyponatremia, the urine
      sodium level elevated to 73 mEq/l. So the urine osmolarity elevated to 752
      mOsm/l, too. In addition to these data, edema and dehydration were absent, and
      both renal and adrenal function were normal. So we diagnosed that this abnormal
      conditions-hyponatremia with corresponding serum hypoosmolality and an
      inappropriately high urinary osmolality due to continued sodium excretion was
      induced by SIADH. Fluid restriction and antibiotics therapy for pneumonia
      resulted in an appropriate rise in the serum sodium level to 138 mEq/l on the
      postoperative day 21. To avoid catastrophic outcome in the cases of hyponatremia
      after surgery, it is important to remember that hyponatremia may be induced by
      SIADH.

PMID- 20141083
TI  - [Chordoma which was found as a solitary lung tumor].
AB  - We report a rare case of chordoma which was found as a well-circumscribed lesion
      on chest X-ray films without any symptoms, and removed surgically. According to
      immunohistochemical examination, it has both of epithelial and mesenchymal cell
      nature, with characteristically positivestaining of S-100. Therefore, it was
      diagnosed as a lung metastasis of chordoma. The primary focus was unclear in
      magnetic resonance imaging (MRI) and the whole body positron emission tomography
      computed tomography (PET-CT) inspection. The possibility to be primary lung
      chordoma can not be denied.

PMID- 20141084
TI  - [Surgically treated tracheo-innominate artery fistula].
AB  - Tracheo-innominate artery fistula (TIF) is one of the highly lethal complications
      after the tracheostomy. We report a case of successful surgical treatment of TIF
      4-year after the tracheostomy due to subacute sclerosing panencephalitis. Once
      the bleeding was controlled by the position and the high pressure of the
      tracheostomy tube cuff, but was not able to be controlled 24-hour after the
      hospitalization. At surgery, innominate artery was clamped simply at its origin
      under a median sternotomy. The each side orifice of the fistula was closed
      directly. The thymus was interposed between the innominate artery and the trachea
      to prevent the infection and the re-adhesion. After surgery, the cerebral
      infarction due to the procedure was not detected by the brain computed tomography
      (CT) and also the stenosis of the innominate artery was not detected by the chest
      enhanced CT.

PMID- 20141085
TI  - [Catamenial pneumothorax; report of a case].
AB  - A 40-year-old female had right-sided pneumothorax. She was treated with a chest
      tube. On the 2nd day, her menstruation started. Because of a persistent air leak,
      she underwent a thoracoscopic operation on the 15th day. During the operation, we
      noted a pulmonary bulla at the apex and multiple blue berry spots both on the
      visceral pleura and the tendinous part of the diaphragm. We performed a resection
      of the pulmonary bulla, partial diaphragmatic excision plus suture. Section of
      visceral pleura and diaphragm shows ductal structures, which is insistent with
      endometriosis. The serum CA125 level decreased to 39 U/ml. Following surgery,
      oral contraceptives was started and no recurrence was encountered thereafter.

PMID- 20141086
TI  - [Spontaneous hemopneumothorax treated with video-assisted thoracoscopic surgery;
      report of two cases].
AB  - Case 1: A 41-year-old man developed right chest pain. Computed tomography (CT)
      revealed right tension hemopneumothorax. Chest tube was placed in the pleral
      cavity immediately. Because of continuous bleeding and inadequate lung expansion,
      video-assisted thoracic surgery (VATS) was performed on day 11 afer admission.
      Thoracoscopic view clearly showed bleeding point at the thoracic apex. Hemostasis
      was performed and peel was removed for expansion of lung. Case 2: A 38-year-old
      man developed right chest pain and dyspnea. CT revealed right hemopneumothorax.
      Because of massive continuous bleeding, emergent VATS was performed.
      Thoracoscopic view clearly showed bleeding point at the thoracic apex and the
      hemostasis and the resection of bullae was performed. Postoperative course of
      both cases was uneventful. It is thought to be important to consider early
      surgical approach for hemopneumothorax to identify the cause of airleakage before
      forming thick peel on the visceral pleura.

PMID- 20141087
TI  - [Repair of Morgagni's hernia by thoracoscopic surgery; report of a case].
AB  - An 84-year-old woman visited a local clinic with the complaint of upper abdominal
      pain and was referred to our hospital because of a suspected mediastinal tumor.
      Chest and abdominal computed tomography (CT) scanning were performed and
      Morgagni's hernia that contained omentum was identified on multiplanar
      reconstruction (MPR) images. Repair surgery was performed via mini-thoracotomy
      with thoracoscopy. The omentum witch was adherent to the hernial sac in the
      thorax was carefully dissected and was replaced in the abdomen. The diaphragmatic
      defect was closed and was reinforced with an expanded proline mesh patch. The
      thoracoscopic surgery with mini-thoracotomy can be a safe and effective method
      for repairing a Morgagni's hernia of which contents are thought to be omentum and
      when intrathoracic adhesions in the hernial sac are suspected.

PMID- 20141088
TI  - [Synchronous multiple lung cancer including a lesion with a thin-walled cavity;
      report of a case].
AB  - A 79-year-old woman underwent video-assisted thoracic surgery (VATS)-left S6
      segmentectomy for left lung cancer (papillary adenocarcinoma, pT1N0M0, stage IA),
      and were followed-up at our hospital. Chest X-ray and chest computed tomography
      (CT) showed ground-glass opacity (GGO) with thin-walled cavity in the right S1, 3
      cm in size and small nodule in the right S2, S3 at 1st operation. The shadow in
      S1 was not changed but nodular lesion in S2, S3 enlarged 7 months later. CT
      guided biopsy revealed well differentiated adenocarcinoma VATS-right upper
      lobectomy was performed and both lesions were diagnosed as "adenocarcinoma with
      mixed subtypes (BAC : acinar type), synchronous multiple lung cancer one of which
      formed thin-walled cavity" histopathologically. The patient was discharged on
      20th-postoperative day and alive without any signs of recurrence for 16 months
      post-operatively.

PMID- 20141089
TI  - [Inflammatory myofibroblast tumor after surgery for primary lung cancer; report
      of a case].
AB  - Inflammatory myofibroblast tumor of the lung is a rare disease, and is difficult
      todistinguish from lung cancer. We report a case of inflammatory myofibroblast
      tumor which was found and resected postsurgery for lung cancer. The patient
      underwent right middle and lower lobectomy due to squamous cell carcinoma in
      right S6 of the lung. A nodular density of 15 mm in diameter was found in the
      right apex on computed tomography (CT) 1 year and 11 months after surgery. The
      right apical mass was resected by partial resection of the residual lobe and
      inflammatory myofibroblast tumor was diagnosed pathologically. It was a case for
      which recurrence or 2nd primary lung cancer was strongly suspected from the
      radiological findings and its rapid growth.

PMID- 20141090
TI  - The new asthma guidelines.

PMID- 20141092
TI  - Nonmalignant chronic pain: taking the time to treat.

PMID- 20141093
TI  - Antibiotics for acute maxillary sinusitis.

PMID- 20141094
TI  - Custom vs. prefabricated orthoses for foot pain.
AB  - Compared with placebo or sham, custom-made foot orthoses modestly reduce foot
      pain from pes cavus (high arch), arthritis, plantar fasciitis, and painful hallux
      valgus. However, there is no evidence that custom orthoses are more effective
      than prefabricated ones.

PMID- 20141095
TI  - Overview of changes to asthma guidelines: diagnosis and screening.
AB  - The Expert Panel Report 3 of the National Asthma Education and Prevention Program
      represents a major advance in the approach to asthma care by emphasizing the
      monitoring of clinically relevant aspects of care and the importance of planned
      primary care, and by providing patients practical tools for self-management.
      Treatment of asthma should be guided by a new system of classification that
      assesses severity at initial evaluation and control at all subsequent visits.
      Asthma severity is determined by current impairment (as evidenced by impact on
      day-to-day activities) and risk of future exacerbations (as evidenced by
      frequency of oral systemic corticosteroid use), and allows categorization of
      disease as intermittent, persistent-mild, persistent-moderate, and persistent
      severe. Initial treatment is guided by the disease-severity category. The degree
      of control is also determined by the analysis of current impairment and future
      risk. Validated questionnaires can be used for following the impairment domain of
      control with patients whose asthma is categorized as "well controlled," "not well
      controlled," and "very poorly controlled." Decisions about medication adjustment
      and planned follow-up are based on the category of disease control. Whereas a
      stepwise approach for asthma management continues to be recommended, the number
      of possible steps has increased.

PMID- 20141096
TI  - Zinc: an essential micronutrient.
AB  - Zinc is an essential micronutrient for human metabolism that catalyzes more than
      100 enzymes, facilitates protein folding, and helps regulate gene expression.
      Patients with malnutrition, alcoholism, inflammatory bowel disease, and
      malabsorption syndromes are at an increased risk of zinc deficiency. Symptoms of
      zinc deficiency are nonspecific, including growth retardation, diarrhea,
      alopecia, glossitis, nail dystrophy, decreased immunity, and hypogonadism in
      males. In developing countries, zinc supplementation may be effective for the
      prevention of upper respiratory infection and diarrhea, and as an adjunct
      treatment for diarrhea in malnourished children. Zinc in combination with
      antioxidants may be modestly effective in slowing the progression of intermediate
      and advanced age-related macular degeneration. Zinc is an effective treatment for
      Wilson disease. Current data do not support zinc supplementation as effective for
      upper respiratory infection, wound healing, or human immunodeficiency virus. Zinc
      is well tolerated at recommended dosages. Adverse effects of long-term high-dose
      zinc use include suppressed immunity, decreased high-density lipoprotein
      cholesterol levels, anemia, copper deficiency, and possible genitourinary
      complications.

PMID- 20141098
TI  - Generalized anxiety disorder: practical assessment and management.
AB  - Generalized anxiety disorder is common among patients in primary care. Affected
      patients experience excessive chronic anxiety and worry about events and
      activities, such as their health, family, work, and finances. The anxiety and
      worry are difficult to control and often lead to physiologic symptoms, including
      fatigue, muscle tension, restlessness, and other somatic complaints. Other
      psychiatric problems (e.g., depression) and nonpsychiatric factors (e.g.,
      endocrine disorders, medication adverse effects, withdrawal) must be considered
      in patients with possible generalized anxiety disorder. Cognitive behavior
      therapy and the first-line pharmacologic agents, selective serotonin reuptake
      inhibitors, are effective treatments. However, evidence suggests that the effects
      of cognitive behavior therapy may be more durable. Although complementary and
      alternative medicine therapies have been used, their effectiveness has not been
      proven in generalized anxiety disorder. Selection of the most appropriate
      treatment should be based on patient preference, treatment success history, and
      other factors that could affect adherence and subsequent effectiveness.

PMID- 20141097
TI  - Cardiomyopathy: an overview.
AB  - Cardiomyopathy is an anatomic and pathologic diagnosis associated with muscle or
      electrical dysfunction of the heart. Cardiomyopathies represent a heterogeneous
      group of diseases that often lead to progressive heart failure with significant
      morbidity and mortality. Cardiomyopathies may be primary (i.e., genetic, mixed,
      or acquired) or secondary (e.g., infiltrative, toxic, inflammatory). Major types
      include dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive
      cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although
      cardiomyopathy is asymptomatic in the early stages, symptoms are the same as
      those characteristically seen in any type of heart failure and may include
      shortness of breath, fatigue, cough, orthopnea, paroxysmal nocturnal dyspnea, and
      edema. Diagnostic studies include B-type natriuretic peptide levels, baseline
      serum chemistries, electrocardiography, and echocardiography. Treatment is
      targeted at relieving the symptoms of heart failure and reducing rates of heart
      failure-related hospitalization and mortality. Treatment options include
      pharmacotherapy, implantable cardioverter-defibrillators, cardiac
      resynchronization therapy, and heart transplantation. Recommended lifestyle
      changes include restricting alcohol consumption, losing weight, exercising,
      quitting smoking, and eating a low-sodium diet.

PMID- 20141099
TI  - Nerve damage from soft tissue injury to the forearm.

PMID- 20141101
TI  - Molecular basis of processing wheat gluten toward biobased materials.
AB  - The unique properties of the wheat grain reside primarily in the gluten-forming
      storage proteins of its endosperm. Wheat gluten's structural and functional
      properties have led to an expanding diversity of applications in food products.
      However, its viscoelastic properties and low water solubility also are very
      interesting features for nonfood applications. Moreover, gluten is annually
      renewable and perfectly biodegradable. In the processing and setting of gluten
      containing products, temperature plays a very important role. In this review, the
      structure and reactivity of gluten are discussed and the importance of sulfhydryl
      (SH) and disulfide (SS) groups is demonstrated. Wheat gluten aggregation upon
      thermosetting proceeds through direct covalent cross-linking in and between its
      protein groups, glutenin and gliadin. Predominant reactions include SH oxidation
      and SH/SS interchange reactions leading to the formation of SS cross-links.
      Additionally, thermal treatment of gluten can result in the formation of other
      than SS covalent bonds. We here review two main technological approaches to make
      gluten-based materials: wet processes resulting in thin films and dry processes,
      such as extrusion or compression molding, exploiting the thermoplastic properties
      of proteins under low moisture conditions and potentially resulting in very
      useful materials. Gluten bioplastics can also be reinforced with natural fibers,
      resulting in biocomposites. Although a lot of progress has been made the past
      decade, the current gluten materials are still outperformed by their synthetic
      polymer counterparts.

PMID- 20141102
TI  - Assimilation of Cd and Cu by the carnivorous plant Sarracenia leucophylla raf.
      fed contaminated prey.
AB  - Many species of carnivorous plants have become endangered through exposure to
      multiple risks such as habitat loss, illegal poaching, and pollution. A potential
      threat to these plants posed by pollution stems from the contamination of their
      invertebrate prey with trace metals. This study examined the potential for prey
      to act as sources of the trace metals Cd and Cu for the pitcher plant Sarracenia
      leucophylla. Cd- and Cu-contaminated Diptera larvae were fed to S. leucophylla
      plants in separate experiments. The results demonstrated that Cd and Cu were
      readily transferred to the shoots of S. leucophylla in a dose-dependent manner.
      While the assimilation of Cu decreased with treatment level, the assimilation of
      Cd did not. Some assimilated Cu appeared to be translocated to the roots, but Cd
      was strongly retained in the shoots, where it was related to a reduction in shoot
      biomass. This suggested that on exposure to Cd-contaminated prey, the plants
      either experienced phytotoxicity or there was disruption of nutrient acquisition
      from the prey. Accumulation of Cu was not related to any sign of phytotoxicity.

PMID- 20141103
TI  - System approach for evaluating the potential yield and plantation of Jatropha
      curcas L. on a global scale.
AB  - Many Jatropha curcas Linnaeus (JCL) plantations have been established in tropical
      and subtropical regions worldwide. To assess the potential of JCL for biofuel
      production, the potential areas for JCL plantations, and the yields of JCL must
      be estimated as accurately as possible. Here, we present a system approach to
      estimate JCL yields, classify yield levels, and estimate productivity of future
      JCL plantations. We used a process-based net primary productivity (NPP) model to
      estimate potential JCL yields. The model estimated that the potential yield of
      JCL dry seed will vary from 0 to 7.62 ton ha(-1) y(-1), in contrast to estimates
      of 1.50-7.80 ton ha(-1) y(-1) from previous assessments. We formulated a zoning
      scheme that takes into account land cover status and potential yield levels. This
      scheme was used to evaluate the potential area and production of future
      plantations at the global, regional, and national levels. The estimated potential
      area of JCL plantations is 59-1486 million hectares worldwide, and the potential
      production is 56-3613 million ton dry seed y(-1). This study provides scientific
      information on global patterns of potential plantation areas and yields, which
      can be used to support bioenergy policy makers to plan commercial-scale JCL
      plantations.

PMID- 20141104
TI  - Direct and indirect water withdrawals for U.S. industrial sectors.
AB  - Effective water management is critical for social welfare and ecosystem health.
      Nevertheless, information necessary to meaningfully assess sustainable water use
      is incomplete. In particular, little information is available on supply chain or
      indirect water use for the production of goods and services in the United States.
      We estimate a vector of water withdrawals for all 428 sectors in the 2002 U.S.
      economic input-output table. The vector was applied using economic input-output
      life cycle assessment (EIO-LCA) methods to estimate direct and indirect water
      withdrawals for each sector's production, both in terms of total withdrawals and
      per dollar of output. Agriculture and power generation account for an
      overwhelming majority of direct water withdrawals (90%). A majority of water use
      (60%) is indirect ("embodied" or "virtual" water) with 96% of the sectors using
      more water indirectly in their supply chains than directly. The food and beverage
      industry accounts for 30% of indirect withdrawals. These results can be useful
      for environmental life cycle assessment of U.S. production and other studies,
      especially to avoid truncation errors due to boundary setting associated with
      process based life cycle impact assessments. However, we conclude that better
      information on water use would be helpful for effective water management.

PMID- 20141105
TI  - Efficient separation of small molecules using a large surface area
      hypercrosslinked monolithic polymer capillary column.
AB  - Monolithic poly(styrene-co-vinylbenzyl chloride-co-divinylbenzene) precursor
      capillary columns have been prepared and then hypercrosslinked to afford a
      monolith containing an array of small pores. This monolithic column exhibited a
      surface area of 663 m(2)/g or more than 1 order of magnitude larger than measured
      for the precursor column. Because it contains mesopores, this monolithic column
      affords good separation of uracil and alkylbenzenes in isocratic mobile phase
      mode and also proved useful for separations in size exclusion mode. A column
      efficiency as high as 73,000 plates/m was determined for uracil. In contrast, the
      presence of mesopores in this hypercrosslinked monolithic column had a
      detrimental effect on the separation of proteins.

PMID- 20141106
TI  - Variations in the spatial distribution of sonoluminescing bubbles in the presence
      of an ionic surfactant and electrolyte.
AB  - It has been established that the addition of sodium dodecylsulfate (SDS) to water
      to a concentration of 1 mM increased the integrated sonoluminescence (SL)
      intensity to a maximum. Moreover, further increase in the SDS concentration to 10
      mM decreased the SL intensity to a level comparable to that obtained for water.
      Photographic images of water and 10 mM SDS have revealed a localized distribution
      of SL bubbles near the liquid surface. For 1 mM SDS, a homogeneous distribution
      of SL bubbles was observed throughout the liquid. In this study, a comprehensive
      investigation was performed to determine the variations in the spatial
      distribution of SL bubbles as a function of SDS concentration, with and without
      the addition of sodium chloride (NaCl). It was found that the integrated SL
      intensity passed through a local minimum as the distribution of SL bubbles
      transformed from an isolated to a homogeneous distribution at 0.25 and 2.4 mM
      SDS. Similar transformations in the spatial distribution of SL bubbles within
      these SDS solutions were also observed upon the addition of a few millimolar
      NaCl. These variations in the spatial distribution of SL bubbles in aqueous
      solutions containing an ionic surfactant and electrolyte were believed to be the
      result of changes in the coalescence stability of bubbles, the attenuation of the
      acoustic wave, and the standing wave ratio.

PMID- 20141107
TI  - Detection of microenvironmental changes induced by protein adsorption onto self
      assembled monolayers using an extended gate-field effect transistor.
AB  - Nonspecific protein adsorption on self-assembled monolayer (SAM) alkanethiols
      with various terminal groups was investigated qualitatively and quantitatively
      using an extended gate-field effect transistor (extended gate-FET). The SAMs were
      characterized by XPS, cyclic voltammogram and water contact angle measurements.
      Changes in gate voltage of 1 mV caused by intrinsic charges of adsorbed protein
      on an undecanethiol SAM in 15 mM Dulbecco's phosphate buffered saline were
      equivalent to 3.6 ng cm(-2), 1.3 ng cm(-2), and 16 ng cm(-2) for bovine serum
      albumin (BSA), lysozyme, and bovine plasma fibrinogen (BPF), respectively, as
      calculated by the Debye-Huckel model. Adsorption coefficients, maximum adsorption
      densities, and Gibbs free energies of adsorption were successfully determined
      using the Langmuir equation. The isotherms depended on the surface properties of
      the SAMs for BSA and lysozyme adsorption. In contrast, changes in gate voltage
      were almost independent of SAM type for BPF adsorption. Adsorption of large
      proteins may not be quantitatively detected because of the large dimensions of
      the biomolecules compared with the Debye length. In summary, the FET measurement
      is a nonlabeling, highly sensitive, and quantitative method for detecting
      nonspecific adsorption of small proteins with dimensions that are comparable to
      the Debye length of a solution.

PMID- 20141108
TI  - Preliminary study of the influence of environment conditions on the successive
      hydrogenations of CO.
AB  - The successive hydrogenation of CO has been investigated by two methods. The
      first is hydrogenation of a CO surface. The second is co-injection of CO
      molecules and H atoms. Both methods have been performed at 3 and 10 K. In the
      first method, the interaction of H atoms with solid CO at 10 K shows that CO is
      consumed to form H(2)CO and CH(3)OH. No trace of species such as HCO and CH(3)O
      is detected. No product was observed when the same experiment was performed at 3
      K. In the second method, when H and CO are codeposited at 10 K, HCO and CH(3)O
      are observed. In fact, the yield of these intermediate species depends on the
      amount of the H radicals interacting with CO molecules. At 3 K, the presence of
      H(2) in the solid screens the hydrogenation reaction. This causes a termination
      for the reaction in the stage of the formation of HCO and H(2)CO. At 10 K, H(2)
      cannot condense, and the reaction between CO and H is total. In this case,
      species such as HCO, H(2)CO, CH(3)O, and CH(3)OH are observed.

PMID- 20141109
TI  - Spatial conformation and charge recombination properties of polythiophene
      derivatives with thienylene-vinylene side chains investigated by static and
      femtosecond spectroscopy.
AB  - We report herein the photophysics of three two-dimensional polythiophene
      derivatives, with different lengths of thienylene-vinylene conjugated side
      chains, in comparison with regioregular poly(3-hexylthiophene) (P3HT). In
      solution, an evolution from stimulated emission to photoinduced absorption (PIA)
      at emission peak is discovered with increasing length of side chains, indicating
      larger steric hindrance by longer side chains. The exciton lifetime is reduced by
      a factor of five when the thienylene-vinylene side chain is prolonged to three
      units. In the film form, we investigate the dynamics of the two PIA bands,
      assigned to intrachain exciton and interchain polaron pairs, respectively. The
      analysis of the dynamics suggests that their intrachain exciton decays are
      similar to the one-dimensional P3HT. The recombination possibility of delocalized
      interchain polaron pairs occurring in 0.9 ps is reduced with longer thienylene
      vinylene side chain samples. Compared with regioregular P3HT film, which self
      organizes to form lamellae crystal morphology, the morphologies of these three
      two-dimensional polythiophenes are amorphous, attributed to the large steric
      hindrance caused by the existence of side chains. This design of polythiophene
      derivatives provides the reduction of recombination possibility for delocalized
      interchain polaron pairs generated in the polymer.

PMID- 20141110
TI  - Ligand-free open-closed transitions of periplasmic binding proteins: the case of
      glutamine-binding protein.
AB  - The ability to undergo large-scale domain rearrangements is essential for the
      substrate-binding function of periplasmic binding proteins (PBPs), which are
      indispensable for nutrient uptake in Gram-negative bacteria. Crystal structures
      indicate that PBPs typically adopt either an "open" unliganded configuration or a
      "closed" liganded one. However, it is not clear whether, as a general rule, PBPs
      remain open until ligand-induced interdomain closure or are in equilibrium with a
      minor population of unliganded, closed species. Evidence for the latter has been
      recently reported on maltose-binding protein (MBP) in aqueous solution [Tang, C.,
      et al. (2007) Nature 449, 1078-1082] via paramagnetic relaxation enhancement
      (PRE), a technique able to probe lowly populated regions of conformational space.
      Here, we use PRE to study the unliganded open-closed transition of another PBP:
      glutamine-binding protein (GlnBP). Through a combination of domain structure
      knowledge and intermolecular and concentration dependence PRE experiments, a set
      of surface residues was found to be involved in intermolecular interactions.
      Barring such residues, PRE data on ligand-free GlnBP, paramagnetically labeled at
      two sites (one at a time), could be appropriately explained by the unliganded,
      open crystal structure in that it both yielded a good PRE fit and was not
      significantly affected by PRE-based refinement. Thus, contrary to MBP, our data
      did not particularly suggest the coexistence of a minor closed conformer. Several
      possibilities were explored to explain the observed differences in such closely
      structurally related systems; among them, a particularly interesting one arises
      from close inspection of the interdomain "hinge" region of various PBPs: strong
      hydrogen bond interactions discourage large-scale interdomain dynamics.

PMID- 20141111
TI  - Extended Morse function model for angle-dependent hydrogen bond in protein
      protein interactions.
AB  - Backbone-backbone, backbone-asparagine, and serine-backbone hydrogen bonds (HBs)
      are the most abundant interactions at the interface of protein-protein complex.
      Here, we propose an angle-dependent potential energy function for these HBs
      constructed by the product of the radial and the angular Morse functions whose
      various parameters are optimized with high-level density functional theory (DFT)
      calculations. The new angular variables, the interatomic distance between the
      donor and the acceptor atoms (R(theta)) and that between the hydrogen and the
      base atom of the acceptor (R(phi)), are employed to define the angular Morse
      functions. The angular part in the new potential function is found to be
      comparable in the magnitude of energy values to the radial one, which is
      consistent with the significant angular dependence of HBs. The HB binding
      energies calculated with the new potential function compare well with those
      obtained by high-level DFT calculations with the associated squared correlation
      coefficients ranging from 0.82 to 0.85. This agreement indicates the suitability
      of the new energy functions as a potential function for HB in modeling the
      protein-protein interactions.

PMID- 20141112
TI  - Efficient synthesis of symmetrical alpha,alpha-disubstituted beta-amino acids and
      alpha,alpha-disubstituted aldehydes via dialkylation of nucleophilic beta-alanine
      equivalent.
AB  - Homologation of the nucleophilic beta-alanine equivalent beta-Ala Ni(II)-PABP
      [Ni(II) complex of beta-alanine Schiff base with 2-[N-(alpha
      picolyl)amino]benzophenone (PABP), 1] via alkyl halide alkylation was
      systematically studied as a general method for preparing symmetrically
      alpha,alpha-disubstituted beta-amino acids. The dialkylation reactions could be
      easily performed and did not require inert atmosphere, dried solvents, and low
      temperatures, thereby affording the benefits of operationally convenient
      experimental procedure and high atom economy. Further, the methodology developed
      by us can also be used to generate symmetrical alpha,alpha-disubstituted
      aldehydes through an alternative decomposition method.

PMID- 20141113
TI  - Are sp lithiated carbons more nucleophilic than sp2 or sp3 ones? A comparative
      DFT study of the condensation of propynyllithium aggregates on formaldehyde.
AB  - The interaction between 1-propynyllithium, taken as a model of sp organolithium
      compound, and formaldehyde has been investigated with DFT theoretical methods.
      The unsolvated monomer, homogeneous dimer, trimer, tetramer, and hexamer have
      been considered, as well as the mixed aggregates with lithium dimethylamide in
      various oligomeric forms. In most cases, the separate entities, their docking
      complexes, the transition states, and the condensation products have been
      characterized. Overall, the general reaction scheme remains the same whatever the
      hybridization and the aggregation. However, the dimeric sp nucleophiles are
      expected to be more reactive (at least in kinetic conditions), while monomeric
      sp(3) entities would be the best nucleophiles in kinetic and thermodynamic
      conditions, even if its docking is the least exothermic. This work also suggests
      that the aggregation plays a relatively limited role on the model reaction.

PMID- 20141114
TI  - MRI sensing based on the displacement of paramagnetic ions from chelated
      complexes.
AB  - We introduce a mechanism for ion sensing by MRI in which analytes compete with
      paramagnetic ions for binding to polydentate chelating agents. Displacement of
      the paramagnetic ions results in alteration of solvent interaction parameters and
      consequent changes in relaxivity and MRI contrast. The MRI changes can be tuned
      by the choice of chelator. As an example, we show that calcium-dependent
      displacement of Mn(2+) ions bound to EGTA and BAPTA results in a T(1)-weighted
      MRI signal increase, whereas displacement from calmodulin results in a signal
      decrease. The changes are ion selective and can be explained using relaxivity
      theory. The ratio of T(2) to T(1) relaxivity is also calcium-dependent,
      indicating the feasibility of "ratiometric" analyte detection, independent of the
      probe concentration. Measurement of paramagnetic ion displacement effects could
      be used to determine analyte ion concentrations with spatial resolution in opaque
      specimens.

PMID- 20141115
TI  - Ruthenium intermetallics grown from La-Ni flux: synthesis, structure, and
      physical properties.
AB  - Crystals of three new intermetallic compounds were grown from reactions of
      ruthenium with other elements in La(0.8)Ni(0.2) eutectic flux. The new boride
      LaRu(2)Al(2)B crystallizes in a filled CeMg(2)Si(2) structure type (P4/mmm, a =
      4.2105(5) A, c = 5.6613(8); Z = 1, R(1) = 0.014), with Ru atoms forming a planar
      square net; B atoms center alternating Ru squares, which is an unusual
      coordination of boron by transition metals. Al atoms connect the Ru(2)B layers,
      forming large voids where La ions reside. The chemical bonding analysis using the
      electron localization function (ELF) reveals two-center covalent bonding between
      Al atoms, an absence of direct Ru-Ru interactions, and three-centered bonds
      between Ru and B or Al atoms. The band structure calculation shows LaRu(2)Al(2)B
      to be metallic, which is in agreement with the observed temperature independent
      paramagnetism and heat capacity data. The crystal structure of La(2)Ni(2
      x)Ru(x)Al (HT-Pr(2)Co(2)Al-type; x = 0.21(1) and x = 0.76(1); C2/c; a = 9.9001(3)
      A, b = 5.7353(1) A, c = 7.8452(2) A, beta = 104.275(1); Z = 4, R(1) = 0.016 for x
      = 0.76(1)) features infinite [Ni(2-x)Ru(x)Al] spiral-twisted chains composed of
      Al(2)M(2)-rhombic units (M = Ni/Ru) seen in many La-Ni-Al intermetallics. The
      structure of La(6)SnNi(3.67)Ru(0.76)Al(3.6) (Nd(6)Co(5)Ge(2.2)-type; P6m2, a =
      9.620(1) A, c = 4.2767(9) A; Z = 1, R(1) = 0.015) is composed of a three
      dimensional [Ni(3.67)Ru(0.76)Al(3.6)](3)(infinity) network with large hexagonal
      channels accommodating interconnected tin-centered lanthanum clusters Sn@La(9).

PMID- 20141117
TI  - Systematic study of modifications to ruthenium(II) polypyridine dyads for
      electron injection enhancement.
AB  - Spatial localization of excited-state electrons in transition-metal complexes
      used as photocatalysts or dye sensitizers in solar cells is important for
      efficient electron injection into the metal oxide nanoparticles. We use density
      functional theory to investigate the excited states in a prototype catalyst
      chromophore assembly [(bpy)(H(2)O)Ru(tpy-tpy)Ru(tpy)](4+)
      ([Ru(tpy)(bpy)(H(2)O)](2+) = catalyst, [Ru(tpy)(2)](2+) = chromophore, tpy =
      2,2':6',2''-terpyridine, and bpy = 2,2'-bipyridine) and a series of related
      compounds. We explore several bridging ligand and terminal tpy ligand
      modifications of the prototype assembly, with the aim of inducing electronic
      excitations into the terminal tpy ligand upon irradiation with visible light. The
      excitations into the terminal ligand (i.e., ligand covalently attached to the
      semiconductor in the photocatalytic synthetic cell) should, in turn, enhance
      electron injection into the semiconductor. Our results suggest that both
      introduction of a spacer group (such as phenylene or alkane) into the tpy-tpy
      bridge and replacement of the terminal tpy group by a more extended pi-conjugated
      ligand are necessary to shift the electronic excitations from the bridging ligand
      into the terminal ligand. These results have implications for the design of
      photocatalysts and dye-sensitizer assemblies based on ruthenium(II) terpyridine
      compounds.

PMID- 20141116
TI  - Conformations of some large-ring cyclodextrins derived from conformational search
      with molecular dynamics simulations and principal component analysis.
AB  - Principal component analysis (PCA) was applied for postprocessing of trajectories
      from conformational search, based on 50.0 ns molecular dynamics (MD) simulations,
      with the purpose to elucidate the conformations of some large-ring cyclodextrins
      (LR-CDs), CDn (n = 24, 25, 26, 27, 28, 29). The dominant PCA modes for concerted
      motions of the macroring atoms were monitored in a lower-dimension subspace. The
      first 10 lowest indexed modes describe more than 90% of the total atomic motions
      in all cases, with about 85% (CD27, CD29) to more than 90% (CD24, CD25)
      contribution coming from the six highest-eigenvalue principal components.
      Representative average geometries of the cyclodextrin macrorings were also
      obtained for the whole simulation and for the five 10.0 ns time intervals of the
      simulation. Two conformations for CD26, the largest LR-CD for which X-ray data is
      available, are characterized by possessing, respectively, one and two helical
      turns. Resemblance to computed representative conformations of CD26 in water was
      found for CD27 and CD28, with the similarity being better expressed for the
      former case. Only CD24, among the two smaller size LR-CDs, displays resemblance
      during short simulation intervals to one of the conformations of CD26. The
      formation of small loops of six to seven glucose units is a favorable deformation
      mode of the macrorings. Besides, once a small loop of six to seven glucoses is
      formed, the next natural mode for deformation of the macromolecule is toward the
      creation of a short helix that further enhances the stability of the structure.
      The average geometry of CD29 has no likeness at all to the conformations of CD26.
      Thus, the difference of three glucose units between CD26 and CD29 already
      influences significantly the shape of the most probable conformation.

PMID- 20141118
TI  - One-dimensional hypersonic phononic crystals.
AB  - We report experimental observation of a normal incidence phononic band gap in one
      dimensional periodic (SiO(2)/poly(methyl methacrylate)) multilayer film at
      gigahertz frequencies using Brillouin spectroscopy. The band gap to midgap ratio
      of 0.30 occurs for elastic wave propagation along the periodicity direction,
      whereas for inplane propagation the system displays an effective medium behavior.
      The phononic properties are well captured by numerical simulations. The porosity
      in the silica layers presents a structural scaffold for the introduction of
      secondary active media for potential coupling between phonons and other
      excitations, such as photons and electrons.

PMID- 20141119
TI  - Synthesis of polycyclic nitrogen heterocycles via alkene
      aminopalladation/carbopalladation cascade reactions.
AB  - A new method for the synthesis of tricyclic nitrogen heterocycles from N,2
      diallylaniline derivatives is described. These transformations proceed via
      sequential alkene aminopalladation of an intermediate L(n)Pd(Ar)(NRR') species
      followed by alkene carbopalladation of the resulting L(n)Pd(Ar)(R) complex. Both
      alkene insertion steps occur in preference to C-N or C-C bond-forming reductive
      elimination. An unusual 1,3-palladium shift occurs when 2-Allyl-N-(2
      vinylphenyl)aniline is employed as substrate, which yields a tetracyclic molecule
      with three contiguous stereocenters.

PMID- 20141120
TI  - An effective method for allylic oxidation of Delta5-steroids using tert-butyl
      hydroperoxide.
AB  - An allylic oxidation method for Delta(5)-steroids using TBHP as oxidant with a 2
      quinoxalinol salen Cu(II) complex as catalyst is reported. A variety of Delta(5)
      steroidal substrates are selectively oxidized to the corresponding enones.
      Excellent yields are achieved (up to 99% under optimized conditions) while
      significantly reducing reaction times required as compared to other current
      methods.

PMID- 20141121
TI  - Evaluation of the biosynthetic proposal for the synthesis of marineosins A and B.
AB  - The first synthetic efforts toward marineosins A and B, novel spiroaminals from a
      Streptomyces actinomycete, are described by evaluation of the proposed
      biosynthesis. The hypothesized biosynthetic C1-C25 Diels-Alder substrate was
      prepared in 8 steps in 5.1% overall yield; however, the proposed biomimetic
      inverse-electron-demand hetero-Diels-Alder reaction failed to deliver the
      marineosin core. Molecular mechanics supports this observation.

PMID- 20141122
TI  - A general approach for preparation of polymer-supported chiral organocatalysts
      via acrylic copolymerization.
AB  - Polymer-supported chiral organocatalysts, as well as most other forms of
      immobilized catalysts, are traditionally prepared by a postmodification approach
      where modified catalyst precursors are anchored onto prefabricated polymer beads.
      Herein, we report an alternative and more scalable approach where polymer
      supported chiral enamine and iminium organocatalysts are prepared in a bottom-up
      fashion where methacrylic functional monomers are prepared in an entirely
      nonchromatographic manner and subsequently copolymerized with suitable comonomers
      to give cross-linked polymer beads. All syntheses have been conducted on
      multigram scale for all intermediates and finished polymer products, and the
      catalysts have proven successful in reactions taking place in solvents spanning a
      wide range of solvent polarity. While polymer-supported proline and prolineamides
      generally demonstrated excellent results and recycling robustness in asymmetric
      aldol reactions of ketones and benzaldehydes, the simplest type of
      Jorgensen/Hayashi diarylprolinol TMS-ether showed excellent selectivity, but
      rather sluggish reactivity in the Enders-type asymmetric cascade. The polymer
      supported version of the first-generation MacMillan imidazolidinone had a pattern
      of reactivity very similar to that of the monomeric catalyst, but is too unstable
      to allow recycling.

PMID- 20141123
TI  - Conjugated oligoyne-bridged [60]fullerene molecular dumbbells: syntheses and
      thermal and morphological properties.
AB  - A series of linear and star-shaped pi-conjugated oligomer hybrids (2-5) composed
      of an oligoyne core, ranging from 1,3-butadiyne to 1,3,5,7,9,11-dodecahexayne,
      and fullerenyl end-capping groups has been synthesized and studied. The molecular
      structures of these fullerene-oligoyne hybrids were assembled through three key
      reactions: Pd-catalyzed cross-coupling, Cu-catalyzed oxidative homocoupling, and
      an in situ alkynylation reaction on [60]fullerene. The properties of these
      compounds were investigated by UV-vis spectroscopy, differential scanning
      calorimetry (DSC), and atomic force microscopy (AFM) with the purpose of
      understanding the thermal reactivity arising from the oligoyne moieties as well
      as the morphological properties on surface. Our study shows that these fullerene
      oligoyne hybrids tend to aggregate in different morphologies, including
      nanospheres, nanoflakes, and continuous thin films, while the morphological
      properties appear to be subject to the influence of molecular factors such as
      oligomer chain length, solubilizing alkylphenyl groups, and the thermal
      reactivity of the oligoyne unit. The correlation between molecular property and
      interfacial aggregation behavior evinced by these fullerene-oligoyne hybrids
      suggests a viable approach to exert bottom-up control over the structures and
      properties of fullerene based nanomaterials.

PMID- 20141124
TI  - Correlation between surface area and photocatalytic activity for acetaldehyde
      decomposition over bismuth tungstate particles with a hierarchical structure.
AB  - The photocatalytic oxidative decomposition of gaseous acetaldehyde (AcH) in air
      under visible light irradiation (wavelength >400 nm) was driven by bismuth
      tungstate (Bi(2)WO(6)) polycrystalline particles with a hierarchical structure,
      flake-ball particles, prepared by hydrothermal reaction at various temperatures.
      Complete decomposition of AcH into CO(2) was proven for all of the flake-ball
      particle photocatalysts. The rate of CO(2) liberation was increased in
      proportional to the specific surface area for flake-ball particles with similar
      high degrees of crystallinity. Kinetic analysis assuming Langmuirian adsorption
      of AcH revealed that the initial rate of photocatalytic decomposition could be
      reproduced by first-order kinetics with respect to the amount of surface-adsorbed
      AcH. A linear relationship between the photocatalytic activity and surface area
      of photocatalysts under conditions in which other physical properties such as the
      photoabsorption property, crystalline content, exposed crystal facets, and
      secondary particle size are almost the same was experimentally revealed.

PMID- 20141125
TI  - Comparative theoretical study of 1,3-dipolar cycloadditions of allyl-anion type
      dipoles to free and Pt-bound nitriles.
AB  - 1,3-Dipolar cycloadditions of a series of 12 allyl-anion type 1,3-dipoles X=Y(+)
      Z(-) (X, Z = CH(2), NH, O; Y = N(Me), O) to acetonitrile MeC[triple bond]N, both
      free and coordinated to Pt(II) and Pt(IV) in the complexes trans
      [PtCl(n)(NCMe)(2)] (n = 2, 4), were investigated by theoretical methods. The
      reactivity increases along the following sequence of dipoles, the first three
      being inert toward nitriles: ON(Me)O < NHN(Me)O < NHN(Me)NH < CH(2)N(Me)O < OOO
      approximately NHONH < CH(2)N(Me)NH < NHOO < CH(2)N(Me)CH(2) < CH(2)OCH(2)
      approximately CH(2)ONH < CH(2)OO. The thermodynamic stability of the
      cycloaddition products (reaction energies) inversely correlates with the
      activation energies with exception of dioxadiazoles N=C(Me)OO NH which cannot
      exist in the uncoordinated state. A complete ortho selectivity of these reactions
      is predicted. Coordination of MeCN to platinum accelerates the reactions of
      CH(2)N(Me)CH(2), CH(2)ONH, and particularly CH(2)N(Me)O and CH(2)N(Me)NH and
      stabilizes the corresponding products. Coordination accelerates the reactions of
      CH(2)OCH(2), CH(2)OO, and NHONH only slightly and inhibits the reactions of NHOO
      and OOO. The cycloadditions of nitrones to nitriles are potentially interesting
      for dynamic combinatorial chemistry. The details of the reaction mechanisms and
      correlations of activation and reaction energies, synchronicity, and charge
      transfer vs dipole nature, FMO energies, atomic charges, HSAB properties,
      distortion energies, and regioisomeric pathways are discussed.

PMID- 20141127
TI  - Transformation of stable glasses into supercooled liquids: growth fronts and
      anomalously fast liquid diffusion.
AB  - Physical vapor deposition onto substrates near 0.85T(g) can prepare organic
      glasses with low enthalpy, high density, and high thermal stability. Isotopically
      labeled multilayer films of tris(naphthyl)benzene and indomethacin stable glasses
      were prepared and secondary ion mass spectrometry was used to study the evolution
      of these materials upon heating above T(g). In contrast to ordinary glasses, when
      stable glasses are held above T(g) they transform to a liquid via a growth front
      mechanism. In these experiments, growth fronts are initiated at the free surface
      of the glass and in some cases at the glass/substrate interface or an internal
      interface in the glass. For tris(naphthyl)benzene, the velocity of this growth
      front is observed to be nearly independent of the stability of the glass.
      Diffusion in the liquid that results from the growth front is initially 2-5 times
      faster than for the equilibrium supercooled liquid at the same temperature; the
      nature of this liquid is unclear. Under some circumstances, the slow evolution of
      this unusually mobile liquid into the equilibrium supercooled liquid can be
      observed.

PMID- 20141126
TI  - Electrochemistry of conductive polymers. 45. Nanoscale conductivity of PEDOT and
      PEDOT:PSS composite films studied by current-sensing AFM.
AB  - [Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)] (PEDOT:PSS, Baytron P)
      composite films were prepared under various conditions and their conductivities
      were studied by the current-sensing atomic force microscopy (CS-AFM) technique.
      Topographic and current images of pristine and additive-treated PEDOT:PSS as well
      as electrochemically synthesized PEDOT films were obtained in nanoscale using the
      CS-AFM. The as-prepared pristine PEDOT:PSS films showed a low population of
      conductive spots isolated by large insulating regions; both their population and
      the conductivities increased upon addition of a few additives to the PEDOT:PSS
      solution before spin-coating. From the current-voltage (I-V) traces recorded at a
      few representative spots of different electronic states, much improved pathways
      for charge percolation appeared to have been established in the additive-treated
      films. Electrochemically prepared PEDOT films showed much better electrical
      properties compared with spin-casted films of chemically prepared polymers. The
      conductivity of all these films was shown to be significantly enhanced by the
      electrochemical doping process.

PMID- 20141128
TI  - Differentially protected diboron for regioselective diboration of alkynes:
      internal-selective cross-coupling of 1-alkene-1,2-diboronic acid derivatives.
AB  - A differentially protected diboron bearing the naphthalene-1,8-diaminato group on
      one of the two boron atoms undergoes highly regioselective diboration with
      terminal alkynes in the presence of Pt or Ir catalysts, giving 1-alkene-1,2
      diboronic acid derivatives in which the less reactive B(dan) group is located at
      the terminal position. The products undergo selective Suzuki-Miyaura coupling
      with aryl bromides at the internal boronyl group, leading to the formation of 2,2
      disubstituted alkenylboronic acid derivatives.

PMID- 20141130
TI  - Mesoporous Co3O4 and Au/Co3O4 catalysts for low-temperature oxidation of trace
      ethylene.
AB  - Low-temperature catalysts of mesoporous Co(3)O(4) and Au/Co(3)O(4) with high
      catalytic activities for the trace ethylene oxidation at 0 degrees C are reported
      in this paper. The catalysts were prepared by using the nanocasting method, and
      the mesostructure was replicated from three-dimensional (3D) cubic KIT-6 silicas.
      High resolution transmission electron microscopy (HRTEM) studies revealed that
      {110} facets were the exposed active surfaces in the mesoporous Co(3)O(4),
      whereas the Co(3)O(4) nanosheets prepared by the precipitation method exhibited
      the most exposed {112} facets. We found that the mesoporous Co(3)O(4) was
      significantly more active for ethylene oxidation than the Co(3)O(4) nanosheets.
      The results indicated that the crystal facet {110} of Co(3)O(4) played an
      essential role in determining its catalytic oxidation performance. The
      synthesized Au/Co(3)O(4) materials, in which the gold nanoparticles were
      assembled into the pore walls of the Co(3)O(4) mesoporous support, exhibited
      stable, highly dispersed, and exposed gold sites. Gold nanoparticles present on
      Co(3)O(4) readily produced surface-active oxygen species and promoted ethylene
      oxidation to achieve a 76% conversion at 0 degrees C, which is the highest
      conversion reported yet.

PMID- 20141131
TI  - Live-cell one- and two-photon uncaging of a far-red emitting acridinone
      fluorophore.
AB  - Total synthesis and photophysical properties of PENB-DDAO, a photoactivatable 1,3
      dichloro-9,9-dimethyl-9H-acridin-2(7)-one (DDAO) derivative of a far-red emitting
      fluorophore, are described. The photoremovable group of the DDAO phenolic
      function comprises a donor/acceptor biphenyl platform which allows an efficient
      (> or = 95%) and rapid (< 15 micros time-range) release of the fluorescent signal
      and displays remarkable two-photon uncaging cross sections (delta(a) x Phi(u) =
      3.7 GM at 740 nm). PENB-DDAO is cell permeable as demonstrated by the triggering
      of cytoplasmic red fluorescent signal in HeLa cells after one-photon irradiation
      (lambda(exc) around 360 nm) or by the generation of a red fluorescent signal in a
      delineated area of a single cell after two-photon photoactivation (lambda(exc) =
      770 nm).

PMID- 20141132
TI  - Cyclobutanone analogues of beta-lactams revisited: insights into conformational
      requirements for inhibition of serine- and metallo-beta-lactamases.
AB  - The most important mode of bacterial resistance to beta-lactam antibiotics is the
      expression of beta-lactamases. New cyclobutanone analogues of penams and penems
      have been prepared and evaluated for inhibition of class A, B, C, and D beta
      lactamases. Inhibitors which favor conformations in which the C4 carboxylate is
      equatorial were found to be more potent than those in which the carboxylate is
      axial, and molecular modeling studies with enzyme-inhibitor complexes indicate
      that an equatorial orientation of the carboxylate is required for binding to beta
      lactamases. An X-ray structure of OXA-10 complexed with a cyclobutanone confirms
      that a serine hemiketal is formed in the active site and that the inhibitor
      adopts the exo envelope. An unsaturated penem analogue was also found to enhance
      the potency of meropenem against carbapenem-resistant MBL-producing strains of
      Chryseobacterium meningosepticum and Stenotrophomonas maltophilia. These
      cyclobutanones represent the first type of reversible inhibitors to show moderate
      (low micromolar) inhibition of both serine- and metallo-beta-lactamases and
      should be considered for further development into practical inhibitors.

PMID- 20141133
TI  - Na-doped p-type ZnO microwires.
AB  - p-Type ZnO microwires were first synthesized by a simple chemical vapor
      deposition method using Na as the dopant source. p-Type doping was confirmed by
      the electrical transport in single-wire field-effect transistors and low
      temperature photoluminescence. The carrier mobility of the microwires was
      estimated to be approximately 2.1 cm(2) V(-1) S(-1).

PMID- 20141134
TI  - Characterization of radicals formed following enzymatic reduction of 3
      substituted analogues of the hypoxia-selective cytotoxin 3-amino-1,2,4
      benzotriazine 1,4-dioxide (tirapazamine).
AB  - The mechanism by which the 1,2,4-benzotriazine 1,4-dioxide (BTO) class of
      bioreductive hypoxia-selective prodrugs (HSPs) form reactive radicals that kill
      cancer cells has been investigated by steady-state radiolysis, pulse radiolysis
      (PR), electron paramagnetic resonance (EPR), and density functional theory (DFT)
      calculations. Tirapazamine (TPZ, 3-amino BTO, 1) and a series of 3-substituted
      analogues, -H (2), -methyl (3), -ethyl (4), -methoxy (5), -ethoxymethoxy (6), and
      -phenyl (7), were reduced in aqueous solution under anaerobic steady-state
      radiolysis conditions, and their radicals were found to remove the substrates by
      short chain reactions of different lengths in the presence of formate ions.
      Multiple carbon-centered radical intermediates, produced upon anaerobic
      incubation of the compounds with cytochrome P(450) reductase enriched microsomes,
      were trapped by N-tert-butyl-alpha-phenylnitrone and observed using EPR. The
      highly oxidizing oxymethyl radical, from compound 5, was identified, and
      experimental spectra obtained for compounds 1, 2, 3, and 7 were well simulated
      after the inclusion of aryl radicals. The identification of a range of oxidizing
      radicals in the metabolism of the BTO compounds gives a new insight into the
      mechanism by which these HSPs can cause a wide variety of damage to biological
      targets such as DNA.

PMID- 20141135
TI  - Approach to profile proteins that recognize post-translationally modified histone
      "tails".
AB  - Post-translational modifications (PTMs) of histones, proteins onto which DNA is
      packaged, are involved in many biological processes, including transcription,
      recombination, and chromosome segregation. As these PTMs can be dynamic,
      combinatorial, and mediators of weak interactions, the comprehensive profiling of
      all proteins that recognize histone PTMs is a daunting task. Here we describe an
      approach to design probes that can be used to identify proteins that directly
      interact with modified histones. Protein structure was used to guide the
      introduction of a photo-cross-linker in the probe, so as to convert weak
      interactions into covalent linkages. The probe also included an alkyne group to
      facilitate click chemistry-mediated conjugation of reporter tags for the rapid
      and sensitive detection (via rhodamine) and affinity enrichment (via biotin) of
      labeled proteins. In particular, we developed and validated a probe that can
      selectively capture proteins that recognize trimethyled lysine-4 of histone H3
      (H3K4me3) in whole proteomes. A complete profiling of H3K4Me3 binding proteins
      should shed new light on cellular processes regulated by this PTM.

PMID- 20141136
TI  - A metal-catalyzed intermolecular [5+2] cycloaddition/Nazarov cyclization sequence
      and cascade.
AB  - The bicyclo[5.3.0]decane skeleton is one of the most commonly encountered
      bicyclic subunits in nature and the core scaffold of a wide range of targets of
      structural, biological, and therapeutic importance. Prompted by the interest in
      such structures, we report the first studies of metal-catalyzed [5+2]
      cycloadditions of vinylcyclopropanes (VCPs) and enynones. The resultant
      efficiently formed dienone cycloadducts serve as substrates for subsequent
      Nazarov cyclizations and as intermediates for single-operation [5+2]/Nazarov
      serial reactions and catalytic cascades. In many cases the one-flask process can
      be carried out in shorter reaction times and with comparable or superior yields
      to the two-flask procedure. Significantly, a single catalyst can be used to
      mediate both transformations. These [5+2]/Nazarov reaction sequences and cascades
      collectively provide strategically novel and facile access to the
      bicyclo[5.3.0]decane skeleton from simple and readily available components.

PMID- 20141137
TI  - Ultrafast X-ray solution scattering reveals different reaction pathways in the
      photolysis of triruthenium dodecacarbonyl (Ru3(CO)12) after ultraviolet and
      visible excitation.
AB  - Ultrafast (ps) time-resolved X-ray scattering was used to study the structural
      dynamics of Ru(3)(CO)(12) in cyclohexane after photolysis at 260 nm. Two
      intermediates form after 100 ps at the onset of the reaction: Ru(3)(CO)(10) for
      the CO loss channel and Ru(3)(CO)(11)(mu-CO) for the metal-metal cleavage
      channel. In our previous study at 390 nm, by contrast, three intermediates were
      observed simultaneously at the onset of the reaction that all relax back to
      Ru(3)(CO)(12) with different lifetimes. The major difference between photolysis
      at 260 and 390 nm is that in the first case Ru(3)(CO)(10)(mu-CO) is formed by
      bimolecular recombination of Ru(3)(CO)(10) with a free CO in 50 ns, whereas in
      the second case it forms directly from Ru(3)(CO)(12) at the onset of the
      reaction. The differences between the photofragmentation pathways are related to
      the absorption bands available at the two wavelengths. The extrema in the
      difference radial distribution functions (RDFs) are unambiguously assigned by
      decomposing the total signal into contributions from the solutes, the solvent and
      the solute-solvent cross-terms, and also contributions from each candidate
      species. The difference RDFs reveal the depletion of Ru-Ru bonds (2.88 A) in the
      initial Ru(3)(CO)(12) molecule and formation of Ru(3)(CO)(10) as the major
      photoproduct. The high-resolution X-ray (88 keV) scattering pattern of pure
      liquid C(6)H(12) indicates that the solvent dynamics at early time delays is due
      to broadening of the intermolecular interatomic correlations at constant volume,
      whereas during thermal expansion at longer time delays, it results from shifts in
      these correlations.

PMID- 20141138
TI  - Development of a convergent entry to the diazofluorene antitumor antibiotics:
      enantioselective synthesis of kinamycin F.
AB  - We describe a 12-step enantioselective synthetic route to the complex anticancer
      antimicrobial agent kinamycin F (3). Key to the success of the route was the
      development of a three-step sequence for construction of the diazonapthoquinone
      (diazofluorene, blue in structure 3) function of the natural product. This
      sequence comprises fluoride-mediated coupling of a beta-(trimethylsilylmethyl)
      cyclohexenone and halonapthoquinone, palladium-mediated cyclization to construct
      the tetracyclic scaffold of the natural product, and mild diazo-transfer to a
      complex cyclopentadiene to introduce the diazo function. Ortho-quinone methide
      intermediates, formed by reduction and loss of dinitrogen from 3, have been
      postulated to form in vivo, and our approach provides a straightforward synthetic
      pathway to such compounds.

PMID- 20141139
TI  - A concise enantioselective synthesis of the chlorosulfolipid malhamensilipin A.
AB  - The first enantioselective synthesis of a member of the chlorosulfolipid family
      of natural products is reported. All of the polar substituents of malhamensilipin
      A are introduced with high stereoselectivity, and the unique (E)-chlorovinyl
      sulfate is created by a chemo-, regio-, and stereoselective E2 elimination of HCl
      in a reaction that likely has a counterpart in the biosynthesis of this
      fascinating natural product.

PMID- 20141140
TI  - delta(34)S-value measurements in food origin assignments and sulfur isotope
      fractionations in plants and animals.
AB  - The delta(34)S values of biological material, especially food commodities, serve
      as indicators for origin assignments. However, in the metabolism of higher plants
      sulfur isotope fractionations must be expected. As a matter of fact, the
      delta(34)S values of the sulfate- and organic-S, respectively, of Brassicaceae
      and Allium species vegetables showed differences between 3 and 6 per thousand,
      and differences in glucosinolates were between 0 and 14 per thousand. delta(34)S
      value differences of total-S between individual tissues of the same plant were
      approximately 3 per thousand. It is believed that these relatively small and
      variable fractionations are due to the partition of individual S-metabolism steps
      to different plant compartments, where they may occur independently and
      quantitatively. The delta(34)S values of herbivore muscle meat and milk relative
      to the diet and between an animal and its child had trophic shifts of
      approximately 1.5 per thousand. (34)S enrichments of up to 4 per thousand were
      observed for hair, hooves, and horn, an isotope fractionation of -5 per thousand
      between the diet sulfate and cartilage. Therefore, the reported agreements
      between delta(34)S value of biomass and primary S sources are true for only bulk
      material and not for individual compounds or tissues.

PMID- 20141141
TI  - Oxidative stability at high temperatures of oleyol and linoleoyl residues in the
      forms of phosphatidylcholines and triacylglycerols.
AB  - An investigation was carried out into the stability of fatty acyl groups to heat
      induced oxidative changes as affected by their chemical environment. The behavior
      of oleic and linoleic acyl groups when esterified in triacylglycerols (TAGs) and
      phosphatidylcholines (PCs) was evaluated. The monitoring of the oxidative
      degradation using liquid chromatography-mass spectrometry (LC-MS) showed that
      fatty acyl groups are less likely to be oxidized when in the form of PCs than
      when in the form of TAGs. In addition, oxidation products from PCs were more
      stable than those from TAGs. This finding strengthens the idea that the choline
      group in PCs increases the stability of fatty acyl groups to oxidation in
      comparison to TAGs.

PMID- 20141142
TI  - Purification of legumin-like proteins from Coffea arabica and Coffea racemosa
      seeds and their insecticidal properties toward cowpea weevil ( Callosobruchus
      maculatus ) (Coleoptera: Bruchidae).
AB  - Legumin-like proteins from seeds of Coffea arabica (CaL-1 and CaL-2) and Coffea
      racemosa (CrL-1 and CrL-2) were characterized and isolated by gel filtration and
      reverse-phase chromatography. The insecticidal properties of the purified
      proteins were tested against Callosobruchus maculatus using artificial diets.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses
      indicated that CaL-1 is composed of two subunits of 33 and 24 kDa, while CaL-2,
      CrL-1, and CrL-2 were monomeric with a single band of 14 kDa. The LD(50) values
      were 0.5% (w/w) for CaL-1 and 0.3% (w/w) for CaL-2, CrL-1, and CrL-2. ED(50) at
      0.3% was assessed for all protein concentrations. The legumin-like proteins were
      not digested by midgut homogenates of C. maculatus until 8 h of incubation. CaL-1
      and CaL-2 ( C. arabica ) and CrL-1 and CrL-2 ( C. racemosa ) are chitin-binding
      proteins, and their insecticidal properties toward C. maculatus larvae might be
      related to their capacity to bind chitin present in the larval gut and their
      associated low digestibility.

PMID- 20141144
TI  - Influence of brewing method and acidity regulators on the antioxidant capacity of
      coffee brews.
AB  - The antioxidant capacity of coffee brews prepared with different coffeemakers
      (filter, plunger, mocha, and espresso) was measured by colorimetric (total
      phenolic compounds and ABTS) and electron spin resonance (ESR) spectroscopy
      techniques (Fremy's salt and TEMPO). The mocha coffeemaker had the highest yield
      in coffee antioxidant extraction per gram of ground roasted coffee, but espresso
      coffee was richest in terms of antioxidant intake (per milliliter of coffee brew)
      followed by mocha, plunger, and filter. Both Folin-Ciocalteu (total phenolic
      compounds) and ABTS assays reacted with standard solutions of chlorogenic acids
      (CGA) and melanoidins (MO-Ala and MO-Gly). However, Fremy's salt was mainly
      scavenged by chlorogenic acids, whereas the stabilized radical TEMPO was
      effectively scavenged by melanoidins, but not by chlorogenic acids. Thus, ESR
      spectroscopy allows distinguishing between phenolic and nonphenolic antioxidants.
      Moreover, the addition of pH-regulator agents to coffee, such as sodium carbonate
      (75 ppm) and bicarbonate (75 ppm), to extend its shelf life, slightly increases
      the pH, modifying the antioxidant capacity in those coffee brews with the highest
      capacity (mocha and espresso).

PMID- 20141143
TI  - Alternating oligo[(2,3-O-isopropylidene-L-threitol)]-co-[(E,E)-1,4
      bis(styryl)benzene]s: the linear chirality transmission additivity relationship
      in nematic liquid crystals.
AB  - Alternating oligo[2,3-O-isopropylidene-L-threitol]-co-[(E,E)-1,4
      bis(styryl)benzene]s (denoted as 2-6 in the article) show helical twisting power
      (HTP), in 4-pentoxyl-4'-biphenylcarbonitrile (5OCB), linearly proportional to the
      number of the chiral cores in the oligomers. The HTP per chiral core of -1.75
      microm(-1) was recorded in the correlation plot with a correlation coefficient of
      R = 0.99. These results suggested that the C(2) chiral L-threitol cores are
      aligned along the same axis. The comparable linear dichroism (LD) of 0.42 +/-
      0.02 obtained for (rac)-2-5 at 405 nm, and of 0.52 +/- 0.03 for E7, a
      commercially available room temperature nematic solvent, at 347 nm in a parallel
      rubbed cell indicated that the long axis of the bis(styryl)benzene segments is
      more or less parallel to the director of the E7 in the LC matrix. This
      observation is highly exciting because the HTP per core could still be
      maintained, no matter whether the cores are evenly spread in a form of monomer in
      the LC matrix or tightly confined in a polymer. Theoretical treatments about the
      conformations of the dopant in the nematic matrix are discussed.

PMID- 20141145
TI  - Analysis of forchlorfenuron in vegetables by LC/TOF-MS after extraction with the
      buffered QuEChERS method.
AB  - This paper describes the application of liquid chromatography time-of-flight mass
      spectrometry (LC/TOF-MS), with electrospray ionization, for residue analysis of
      forchlorfenuron in tomato, zucchini and watermelon. The assessed method includes
      a sample preparation step based on the buffered QuEChERS approach. The TOF-MS
      fragmentation pattern of forchlorfenuron was studied at different fragmention
      voltages in the range of 120-270 V. Analyses were carried out under full-scan
      conditions by using the extracted ion chromatogram (XIC) of the m/z 248 ion with
      a 0.2 Da window. The linearity of the analytical response across the studied
      range of concentrations (10-500 microg/kg) was excellent, obtaining correlation
      coefficients higher than 0.999, and relative standard deviations of the response
      factors lower than 14%, for the 15 linear calibration curves of forchlorfenuron
      evaluated along the complete validation study. No significant matrix effects were
      observed. The signal-to-noise ratios obtained for the 10 microg/kg
      forchlorfenuron in matrix matched standards were >70 for all three matrices.
      Recovery studies were carried out on spiked tomato, zucchini and watermelon blank
      samples, at three concentration levels (10, 50, and 200 microg/kg) performing
      five replicates at each level. Forchlorfenuron mean recoveries ranged between 80%
      and 87% in watermelon and zucchini, and between 65% and 71% in tomato, obtaining
      in all cases relative standard deviation values lower than 10%. The method
      readily achieved a lowest validated level of 10 microg/kg, which was fit-for
      purpose in residue monitoring applications.

PMID- 20141146
TI  - Identification of potent pyrazolo[4,3-h]quinazoline-3-carboxamides as multi
      cyclin-dependent kinase inhibitors.
AB  - Abnormal proliferation mediated by disruption of the mechanisms that keep the
      cell cycle under control is a hallmark of virtually all cancer cells. Compounds
      targeting complexes between cyclin-dependent kinases (CDKs) and cyclins (Cy) and
      inhibiting their activity are regarded as promising antitumor agents to
      complement the existing therapies. An expansion of pyrazolo[4,3-h]quinazoline
      chemical class oriented to the development of three points of variability was
      undertaken leading to a series of compounds able to inhibit CDKs both in vitro
      and in vivo. Starting from the CDK selective but poorly soluble hit compound 1,
      we succeeded in obtaining several compounds showing enhanced inhibitory activity
      both on CDKs and on tumor cells and displaying improved physical properties and
      pharmacokinetic behavior. Our study led to the identification of compound 59 as a
      highly potent, orally bioavailable CDK inhibitor that exhibited significant in
      vivo efficacy on the A2780 ovarian carcinoma xenograft model. The demonstrated
      mechanisms of action of compound 59 on cancer cell lines and its ability to
      inhibit tumor growth in vivo render this compound very interesting as potential
      antineoplastic agent.

PMID- 20141147
TI  - Piperazinyl glutamate pyridines as potent orally bioavailable P2Y12 antagonists
      for inhibition of platelet aggregation.
AB  - Polymer-assisted solution-phase (PASP) parallel library synthesis was used to
      discover a piperazinyl glutamate pyridine as a P2Y(12) antagonist. Exploitation
      of this lead provided compounds with excellent inhibition of platelet aggregation
      as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and
      physiochemical properties were optimized through modifications at the 4-position
      of the pyridine ring and the terminal nitrogen of the piperazine ring, leading to
      compound (4S)-4-[({4-[4-(methoxymethyl)piperidin-1-yl]-6-phenylpyridin-2
      yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid
      47s with good human PRP potency, selectivity, in vivo efficacy, and oral
      bioavailability. Compound 47s was selected for further preclinical evaluations.

PMID- 20141148
TI  - Calorimetric and computational study of 2- and 3-acetyl-1-methylpyrrole isomers.
AB  - This work reports the enthalpies of formation in the condensed and gas phases of
      2-acetyl-1-methylpyrrole and 3-acetyl-1-methylpyrrole, derived from the standard
      (p(o) = 0.1 MPa) molar enthalpies of combustion, in oxygen, Delta(c)H(m)(o),
      measured by static bomb combustion calorimetry and the standard molar enthalpies
      of vaporization, Delta(l)(g)H(m)(o), at T = 298.15 K, obtained by high
      temperature Calvet microcalorimetry. The theoretically estimated gas-phase
      enthalpies of formation were calculated from high-level ab initio molecular
      orbital calculations at the G3(MP2)//B3LYP level; the computed values compare
      very well with the experimental results obtained in this work and show that the 2
      acetyl-1-methylpyrrole is thermodynamically more stable than the 3-isomer.
      Furthermore, this composite method was also applied in the calculation of bond
      dissociation enthalpies, gas-phase basicities, proton and electron affinities,
      and adiabatic ionization enthalpies.

PMID- 20141149
TI  - Kinetically distinct three red chlorophylls in photosystem I of
      Thermosynechococcus elongatus revealed by femtosecond time-resolved fluorescence
      spectroscopy at 15 K.
AB  - Time-resolved fluorescence spectra of photosystem I (PS-I) trimeric complex
      isolated from a thermophilic cyanobacterium, Thermosynechococcus (T.) elongatus,
      were observed at 15 K over the time range from 100 fs to a few nanoseconds under
      P700-oxidized condition and 10 ps to a few nanoseconds under P700-reduced
      condition. Global-fitting analysis of the data of P700-oxidized condition
      revealed the existence of three kinetically different red chlorophylls (Chls)
      having the energy-transfer times to P700(+) of 6.1 ps (C(6.1 ps)), 140 ps (C(140
      ps)), and 360 ps (C(360 ps)). According to the spectral shape of DAS, C(6.1 ps),
      C(140 ps), and C(360 ps) were assigned to the previously reported red Chls with
      the absorption maxima at 715 nm (C715), 710 nm (C710), and 719 nm (C719),
      respectively. In PS-I containing P700(+), ca. 60 Chls funnel the excitation
      energy into C(6.1 ps) in a subpicosecond time region at 15 K. The analysis of the
      present data together with the conclusions of the previous reports revealed that
      in PS-I containing a neutral P700 the direct energy transfer from the bulk Chls
      to P700 seems to dominate the energy-flow process. Simulation of the energy
      transfer time to P700(+) based on Forster theory suggested the dimeric Chls A32
      B7 and A33-A34 as the most probable candidates for C(140 ps) (C710) and C(360 ps)
      (C719), respectively. C(6.1 ps) (C715) was tentatively assigned to the dimeric
      Chl B24-B25 or A26-A27, for which the fastest energy transfer to P700(+) was
      predicted from the simulation. However, the estimated energy-transfer times to
      P700(+) for these dimeric Chls were 44-46 ps, which were still much slower than
      the observed value of 6.1 ps. A theoretical framework beyond the standard Forster
      theory might be required in order to account for the severe deviation.

PMID- 20141150
TI  - Water hydrogen bond dynamics in aqueous solutions of amphiphiles.
AB  - The hydrogen bond dynamics of water in a series of amphiphilic solute solutions
      are investigated through simulations and analytic modeling with an emphasis on
      the interpretation of experimentally accessible two-dimensional infrared (2D IR)
      photon echo spectra. We evidence that for most solutes the major effect in the
      hydration dynamics comes from the hydrophilic groups. These groups can retard the
      water dynamics much more significantly than can hydrophobic groups by forming
      strong hydrogen bonds with water. By contrast, hydrophobic groups are shown to
      have a very moderate effect on water hydrogen bond breaking kinetics. We also
      present the first calculation of the 2D IR spectra for these solutions. While 2D
      IR spectroscopy is a powerful technique to probe water hydrogen bond network
      fluctuations, interpretations of aqueous solution spectra remain ambiguous. We
      show that a complementary approach through simulations and calculation of the
      spectra lifts the ambiguity and provides a clear connection between the simulated
      molecular picture and the experimental spectroscopy data. For amphiphilic solute
      solutions, we show that, in contrast with techniques such as NMR or ultrafast
      anisotropy, 2D IR spectroscopy can discriminate between waters next to the
      solutes hydrophobic and hydrophilic groups. We also evidence that the water
      dynamics slowdown due to the hydrophilic groups is dramatically enhanced in the
      2D IR spectral relaxation, because these groups can induce a slow chemical
      exchange with the bulk, even when recognized exchange signatures are absent.
      Implications for the understanding of water around chemically heterogeneous
      systems such as protein surfaces and for the interpretation of 2D IR spectra in
      these cases are discussed.

PMID- 20141151
TI  - Ultrafast vibrational spectroscopy of cyanophenols.
AB  - Aromatic compounds with electron-donating or -accepting substituents exhibit
      interesting resonance effects on a variety of chemical reactivities and optical
      properties. To understand such effects and the possible relationship between
      vibrational energy dissipation pathways and resonance structures of aromatic
      compounds, we studied ortho-, meta-, and para-substituted cyanophenols and their
      anionic forms in methanol by using time- and frequency-resolved pump-probe and
      two-dimensional IR spectroscopy, where the nitrile group acts as an IR probe.
      From the measured transient spectra and singular-value decomposition analyses, we
      found that there is a combination band whose frequency is very close to that of
      the nitrile stretch mode. Due to the difference in the lifetimes of these two
      mode excited states, the transient pump-probe spectra commonly show notable blue
      shifting behaviors in time. Comparing the vibrational lifetimes of neutral
      cyanophenols and cyanophenoxide anions in methanol and carrying out quantum
      mechanical/molecular mechanical molecular dynamics simulations to study hydrogen
      bonding dynamics, we found that the vibrational energy of the nitrile stretch
      mode initially relaxes to intramolecular degrees of freedom instead of solvent
      modes. Also, the vibrational anharmonic frequency shifts, intrinsic lifetimes,
      and bandwidths of the nitrile stretch mode and the combination mode in these
      molecular systems are fully characterized, and their relationships with resonance
      structures are discussed. It is believed that the present work sheds light on the
      intrinsic vibrational relaxation process of the nitrile stretch mode in
      cyanophenols, even in the case when their IR spectra are congested by the
      spectrally overlapping combination bands, and the resonance effects of aromatic
      compounds on vibrational dynamics and relaxation processes.

PMID- 20141152
TI  - Fluorescent carrier ampholytes assay for portable, label-free detection of
      chemical toxins in tap water.
AB  - We present a novel method for fluorescence-based indirect detection of analytes
      and demonstrate its use for label-free detection of chemical toxins in a hand
      held device. We fluorescently label a mixture of low-concentration carrier
      ampholytes and introduce it into an isotachophoresis (ITP) separation. The
      carrier ampholytes provide a large number of fluorescent species with a wide
      range of closely spaced effective electrophoretic mobilities. Analytes focus
      under ITP and displace subsets of these carrier ampholytes. The analytes are
      detected indirectly and quantified by analyzing the gaps in the fluorescent
      ampholyte signal. The large number (on the order of 1000) of carrier ampholytes
      enables detection of a wide range of analytes, requiring little a priori
      knowledge of their electrophoretic properties. We discuss the principles of the
      technique and demonstrate its use in the detection of various analytes using a
      standard microscope system. We then present the integration of the technique into
      a self-contained hand-held device and demonstrate detection of chemical toxins (2
      nitrophenol and 2,4,6-trichlorophenol) in tap water, with no sample preparation
      steps.

PMID- 20141153
TI  - Hierarchical assembly of extended coordination networks constructed by novel
      metallacalix[4]arenes building blocks.
AB  - Five interesting metal-organic nanostructures and networks,
      [Ni(4)(HL)(4)(bpy)(py)(H(2)O)(5)](2) x 0.5 H(2)O (1),
      [Co(4)(HL)(4)(bpy)(py)(H(2)O)(5)](2) x 0.5 H(2)O (2), [Ni(4)(HL)(4)(H(2)O)(7)](n)
      x nH(2)O (3), [Ni(4)(HL)(4)(bpy)(2)(H(2)O)(4)](n) (4), and
      [Cd(4)(HL)(4)(H(2)O)](n) (5), were synthesized hydrothermally [H(3)L = 2-(pyridin
      2-yl)-1H-imidazole-4,5-dicarboxylate acid, py = pyridine, and bpy = 4,4'
      bipyridine]. Intriguingly, all compounds consist of novel metallacalix[4]arene
      building blocks M(4)(HL)(4), where doubly deprotonated HL in the same bichelating
      fashion of mu-kN,N':kO,N'' displays a strong coordination orientation by
      cooperation of the 4,5-imidazoledicarboxylate and 2-pyridyl groups. Very
      interestingly, the symmetry of M(4)(HL)(4) and the linkage styles between metal
      nodes and HL in M(4)(HL)(4) are sensitive to the reaction conditions, and the
      resulting structural motifs vary with secondary ligands and metal nodes. In 1 and
      2, two C(1)-symmetric M(4)(HL)(4) units are bpy-bridged into dimeric chiral
      nanomolecules with two different cavities. As deprotonated with NaOH, the
      combination of Ni(II) and HL forms a pseudo-S(4)- or S(4)-symmetric M(4)(HL)(4),
      which further assembles into 1D chiral crystals 3 or rare 3D crystals 4 of bpy
      bridged 5-fold interpenetrating diamondoid architecture with metallacalix[4]arene
      building blocks as novel 4-connecting nodes, and the combination of Cd(II) and HL
      forms an 8-connected C(2)-symmetric M(4)(HL)(4) that fabricates the alpha-Po net
      of 5. Notably, those large M(4)(HL)(4) units are potentially highly connected
      building blocks in a hierarchical assembly of metal-organic networks. Magnetic
      studies disclose antiferromagnetic interactions in M(4)(HL)(4) of 1-4. The
      magnetic data for 1, 3, and 4, all containing isomeric Ni(4)(HL)(4) units, are
      analyzed by an equilateral quadrangle isotropic model combined with the molecular
      field approximation with J = -4.00(2), -3.39(2), and -2.72(3) cm(-1),
      respectively, presenting a stronger comparison between the structure and
      magnetism. The emission of 5 is odd, which perhaps is relative to the bichelating
      fashion of ligand HL and a rare coordination geometry of Cd(II). Moreover, the
      thermal stability and gas sorption properties of these compounds were measured.

PMID- 20141154
TI  - Differential protein levels and post-translational modifications in spinal cord
      injury of the rat.
AB  - Although changes in protein expression in spinal cord injury (SCI) would be of
      pivotal interest, information so far is limited. It was therefore the aim of the
      study to determine protein levels and post-translational modifications in the
      early phase following SCI in the rat. SCI was induced in Sprague-Dawley rats and
      sham operated rats served as controls. A gel-based proteomic approach using two
      dimensional gel electrophoresis followed by quantification with specific software
      and subsequent identification of differentially expressed proteins by nano-ESI-LC
      MS/MS was applied. Proteins of several pathways and cascades were dysregulated in
      SCI: 14-3-3 epsilon protein, dynein light chain 1, and tubulin beta-5 chain
      showed higher levels in SCI, whereas adenylyl cyclase associated protein 1,
      dihydropyrimidinase-related protein 2, F-actin capping protein subunit beta,
      glyceraldehyde-3-phosphate dehydrogenase, stress-induced phosphoprotein 1 and
      transthyretin showed lower levels in the injured tissue. Post-translational
      modifications indicated free oxygen radical attack on proteins in SCI. The
      occurrence of stress is indicated by deranged stress-induced phosphoprotein 1 and
      signaling abnormalities are reflected by adenylyl cyclase-associated protein 1
      and 14-3-3 epsilon protein. The findings propose the involvement of the
      corresponding cascades and challenge further work into aberrant signaling and
      oxidative stress in SCI, which may form the basis for experimental intervention
      for spinal cord trauma.

PMID- 20141155
TI  - Graphene synthesis on cubic SiC/Si wafers. perspectives for mass production of
      graphene-based electronic devices.
AB  - The outstanding properties of graphene, a single graphite layer, render it a top
      candidate for substituting silicon in future electronic devices. The so far
      exploited synthesis approaches, however, require conditions typically achieved in
      specialized laboratories and result in graphene sheets whose electronic
      properties are often altered by interactions with substrate materials. The
      development of graphene-based technologies requires an economical fabrication
      method compatible with mass production. Here we demonstrate for the fist time the
      feasibility of graphene synthesis on commercially available cubic SiC/Si
      substrates of >300 mm in diameter, which result in graphene flakes electronically
      decoupled from the substrate. After optimization of the preparation procedure,
      the proposed synthesis method can represent a further big step toward graphene
      based electronic technologies.

PMID- 20141156
TI  - Optical absorption enhancement in silicon nanohole arrays for solar
      photovoltaics.
AB  - We investigate silicon nanohole arrays as light absorbing structures for solar
      photovoltaics via simulation. To obtain the same ultimate efficiency as a
      standard 300 microm crystalline silicon wafer, we find that nanohole arrays
      require twelve times less silicon by mass. Moreover, our calculations show that
      nanohole arrays have an efficiency superior to nanorod arrays for practical
      thicknesses. With well-established fabrication techniques, nanohole arrays have
      great potential for efficient solar photovoltaics.

PMID- 20141158
TI  - Single-file diffusion of water inside narrow carbon nanorings.
AB  - We use atomistic molecular dynamics (MD) simulations to study the diffusion of
      water molecules confined inside narrow (6,6) carbon nanorings. The water
      molecules form two oppositely polarized chains. It is shown that the effective
      interaction between these two chains is repulsive in nature. The computed mean
      squared displacement (MSD) clearly shows a scaling with time Deltatheta(2)(t)
      approximately t(1/2), which is consistent with single-file diffusion (SFD). The
      time up to which the water molecules undergo SFD is shown to be the lifetime of
      the water molecules inside these chains. Simulations of "uncharged" water
      molecules inside the nanoring show the formation of several water chains and
      yield SFD. These observations conclusively prove that the diffusion is Fickian
      when there is a single chain of water and SFD is observed only when two or more
      chains are present.

PMID- 20141157
TI  - Nanoassembled plasmonic-photonic hybrid cavity for tailored light-matter
      coupling.
AB  - We propose and demonstrate a hybrid cavity system in which metal nanoparticles
      are evanescently coupled to a dielectric photonic crystal cavity using a
      nanoassembly method. While the metal constituents lead to strongly localized
      fields, optical feedback is provided by the surrounding photonic crystal
      structure. The combined effect of plasmonic field enhancement and high quality
      factor (Q approximately 900) opens new routes for the control of light-matter
      interaction at the nanoscale.

PMID- 20141159
TI  - Elastic deformation in ceria nanorods via a fluorite-to-rutile phase transition.
AB  - Atomistic simulations reveal that ceria nanorods, under uniaxial tension, can
      accommodate over 6% elastic deformation. Moreover, a reversible fluorite-to
      rutile phase change occurs above 6% strain for a ceria nanorod that extends along
      [110]. We also observe that during unloading the stress increases with decreasing
      strain as the rutile reverts back to fluorite. Ceria nanorods may find possible
      application as vehicles for elastic energy storage.

PMID- 20141160
TI  - Richard E. Moore (1933-2007).

PMID- 20141161
TI  - John W. Daly (1933-2008).

PMID- 20141162
TI  - Reactions of oxetan-3-tert-butylsulfinimine for the preparation of substituted 3
      aminooxetanes.
AB  - The oxetane ring is useful in drug discovery as a bioisostere for both the
      geminal dimethyl group and the carbonyl group. A convenient, straightforward
      approach to access structurally diverse 3-aminooxetanes through the reactivity of
      oxetan-3-tert-butylsulfinimine and the corresponding sulfinylaziridine is
      described.

PMID- 20141163
TI  - Stereoselective synthesis of a monocyclic peloruside a analogue.
AB  - The stereoselective synthesis of the monocyclic peloruside A analogue 4 has been
      achieved, following a new efficient approach for the introduction of the side
      chain, involving a late-stage addition of vinyl lithium species 7a to aldehyde 8.
      Further key steps are a highly diastereoselective allyltitanation reaction and a
      RCM-based macrocyclization.

PMID- 20141164
TI  - Production of tropane alkaloids during de-differentiation of Scopolia parviflora
      calli.
AB  - The production of tropane alkaloids during differentiation and de-differentiation
      of Scopolia parviflora calli was studied. Tropane alkaloid production drastically
      decreased during calli de-differentiation. Scopolamine (1) production decreased
      after 10 days of culture, whereas that of hyoscyamine (2) decreased during de
      differentiation of root to calli. The production of 1 was enhanced in calli
      undergoing differentiation to shoot after 60 days of culture, reaching a maximum
      by 80 days. However, production of hyoscyamine in regenerated plants was lower.
      The expression level of hyoscyamine 6beta-hydroxylase (H6H), a key biosynthetic
      enzyme for tropane alkaloids, was significantly increased in 4-week-old calli.
      This study suggests that the biosynthesis of tropane alkaloids is regulated
      inversely in de-differentiating Scopolia parviflora calli.

PMID- 20141165
TI  - Au/Ag-catalyzed intramolecular ring-opening of vinylidene-cyclopropanes (VDCPs):
      an easy access to functional tetrahydropyrans.
AB  - An intramolecular ring-opening of vinylidenecyclopropanes (VDCPs) tethered with
      alcohol chains has been established. A series of transition metal catalysts and
      their combinations have been screened under mild conditions, and a cocatalyst
      system consisting of [(Ph(3)PAu)(3)O]BF(4) (4 mol %) and AgOTf (4 mol %) was
      found to catalyze the reaction to completion within 10-30 min in 1,4-dioxane at
      60 degrees C to give allene-functionalized tetrahydropyrans.

PMID- 20141166
TI  - Efficient synthesis of hangman porphyrins.
AB  - A two-step synthetic method has been designed to furnish hangman porphyrins in
      good yields from easily available starting materials. The use of the microwave
      irradiation technique has been found to be valuable for delivering the carboxylic
      acid hanging group in a much simplified and less time-consuming basic ester
      hydrolysis (4 h vs 7 days under harsh acidic conditions). The new route
      facilitates the synthesis of various hangman porphyrins that previously had
      limited or no access.

PMID- 20141167
TI  - Temperature-sensitive reaction of a photosensor protein YcgF: possibility of a
      role of temperature sensor.
AB  - The spectrally silent photoreaction of a blue light sensor protein YcgF, composed
      of the N-terminal BLUF domain and the C-terminal EAL domain, was investigated by
      the time-resolved transient grating method. Comparing photoinduced reactions of
      full-length YcgF with that of the BLUF-linker construct, it was found that a
      major conformation change after photoinduced dimerization is predominantly
      localized on the EAL domain. Furthermore, the photoinduced conformational change
      displayed significant temperature dependence. This result is explained by an
      equilibrium of reactive and nonreactive YcgF species, with the population of
      photoreactive species decreasing as the temperature is lowered in the dark state.
      We consider that the dimer form is the nonreactive species and it is the dominant
      species at lower temperatures. The temperature sensitivity of the photoreaction
      of YcgF suggests that this protein could have a biological function as a
      temperature sensor as well as behaving as a light sensor.

PMID- 20141168
TI  - Identification of core structural residues in the sequentially diverse and
      structurally homologous Bcl-2 family of proteins.
AB  - The Bcl-2 family of proteins regulates the intrinsic pathway of apoptosis and
      plays a significant role in mitochondrial outer membrane permeabilization. Bcl-2
      homologues belonging to both anti- and pro-apoptotic classes have been identified
      in diverse organisms. While anti-apoptotic Bcl-2 proteins possess up to four BH
      sequence domains (BH1-BH4), the pro-apoptotic counterparts have either three BH
      (BH1-BH3) domains or only the BH3 domain. Many anti-apoptotic viral homologues do
      not seem to have any detectable BH homology regions and exhibit a very low level
      of sequence identity with other Bcl-2 family members. However, structures
      determined for several Bcl-2 anti- and pro-apoptotic proteins and their viral
      homologues show a remarkably conserved helical fold characterized by a central
      hydrophobic helix surrounded by five or six amphipathic helices. In this study,
      we have analyzed 16 nonredundant Bcl-2 structures from human, mouse,
      Caenorhabditis elegans, and five different viral species. While the length of the
      central hydrophobic helix is preserved in all the Bcl-2 structures, variations in
      length are observed for other helices. We performed multiple-structure alignment
      of all 16 structures. Eighty structurally equivalent positions, the bulk of them
      in the helical regions, constituted the ungapped blocks in the structure-based
      sequence alignment. Analysis of helix bundle geometry indicates that helix-helix
      packing differed in different Bcl-2 structures. This is presumably to accommodate
      disparate residue substitutions. Residue properties such as solvent
      accessibility, conservation of chemical nature, and/or size and involvement in
      interhelical interactions were analyzed in each position of the ungapped
      alignment regions. A sequence motif made up of small amino acids has been
      detected in the central helix that is proposed to be important for helix-helix
      association. We have found that residues in 22 positions in the helical regions
      are buried, exhibit conservation in hydrophobicity and/or size, and participate
      in interhelical interactions in at least 12 of the 16 structures studied. We also
      found 15 additional positions in which residues exhibit two of the three
      properties investigated. We suggest that these positions constitute the important
      structural core in the diverse Bcl-2 family members and could play a significant
      role in the folding of the protein. Results of our studies have been used in the
      identification of three putative Bcl-2 homologues from three different viral
      organisms. This study will help in the genome-wide identification of hitherto
      unrecognized Bcl-2 family members, especially in viral genomes.

PMID- 20141170
TI  - Syntheses and biological evaluation of irciniastatin A and the C1-C2 alkyne
      analogue.
AB  - Syntheses of both natural (+)- and unnatural (-)-irciniastatin A (aka psymberin)
      as well as a C1-C2 alkyne analogue of (+)-irciniastatin A have been achieved. The
      key features of the syntheses include a highly regioselective epoxide-opening
      reaction and a late-stage assembly of C1-C6, C8-C16, and C17-C25 fragments. (+)
      Alkymberin retained a high level of cytotoxicity, whereas (-)-irciniastatin A
      showed almost no activity. These results suggest that (+)-alkymberin could be a
      useful enantio-differential probe for mode-of-action study.

PMID- 20141171
TI  - Nonaqueous synthesis and photoluminescence of ITO nanoparticles.
AB  - SnO(2) has successfully been doped into octahedral In(2)O(3) nanoparticles using
      a high-temperature nonaqueous reaction. The resultant ITO nanoparticles exhibit a
      particle/crystal decrease in size, sphericity in morphology, and enhancement in
      photoluminescence.

PMID- 20141169
TI  - Levodopa deactivates enzymes that regulate thiol-disulfide homeostasis and
      promotes neuronal cell death: implications for therapy of Parkinson's disease.
AB  - Parkinson's disease (PD), characterized by dopaminergic neuronal loss, is
      attributed to oxidative stress, diminished glutathione (GSH) levels,
      mitochondrial dysfunction, and protein aggregation. Treatment of PD involves
      chronic administration of Levodopa (l-DOPA) which is a pro-oxidant and may
      disrupt sulfhydryl homeostasis. The goal of these studies is to elucidate the
      effects of l-DOPA on thiol homeostasis in a model akin to PD, i.e., immortalized
      dopaminergic neurons (SHSY5Y cells) with diminished GSH content. These neurons
      exhibit hypersensitivity to l-DOPA-induced cell death, which is attributable to
      concomitant inhibition of the intracellular thiol disulfide oxidoreductase
      enzymes. Glutaredoxin (Grx) was deactivated in a dose-dependent fashion, but its
      content was unaffected. Glutathione disulfide (GSSG) reductase (GR) activity was
      not altered. Selective knockdown of Grx resulted in an increased level of
      apoptosis, documenting the role of the Grx system in neuronal survival. l-DOPA
      treatments also led to decreased activities of thioredoxin (Trx) and thioredoxin
      reductase (TR), concomitant with diminution of their cellular contents. Selective
      chemical inhibition of TR activity led to an increased level of apoptosis,
      documenting the Trx system's contribution to neuronal viability. To investigate
      the mechanism of inhibition at the molecular level, we treated the each isolated
      enzyme with oxidized l-DOPA. GR, Trx, and TR activities were little affected.
      However, Grx was inactivated in a time- and concentration-dependent fashion
      indicative of irreversible adduction of dopaquinone to its nucleophilic active
      site Cys-22, consistent with the intracellular loss of Grx activity but not Grx
      protein content after l-DOPA treatment. Overall l-DOPA is shown to impair the
      collaborative contributions of the Grx and Trx systems to neuron survival.

PMID- 20141172
TI  - Low catalyst loadings in olefin metathesis: synthesis of nitrogen heterocycles by
      ring-closing metathesis.
AB  - A series of ruthenium catalysts have been screened under ring-closing metathesis
      (RCM) conditions to produce five-, six-, and seven-membered carbamate-protected
      cyclic amines. Many of these catalysts demonstrated excellent RCM activity and
      yields with as low as 500 ppm catalyst loadings. RCM of the five-membered
      carbamate series could be run neat, the six-membered carbamate series could be
      run at 1.0 M, and the seven-membered carbamate series worked best at 0.2-0.05 M.

PMID- 20141174
TI  - Method for analyte identification using isotachophoresis and a fluorescent
      carrier ampholyte assay.
AB  - We present a novel method for identification of unlabeled analytes using
      fluorescent carrier ampholytes and isotachophoresis (ITP). The method is based on
      previous work where we showed that the ITP displacement of carrier ampholytes can
      be used for detection of unlabeled (nonfluorescent) analytes. We here propose a
      signal analysis method based on integration of the associated fluorescent signal.
      We define a normalized signal integral which is equivalent to an accurate measure
      of the amount of carrier ampholytes which are focused between the leading
      electrolyte and the analyte. We show that this parameter can be related directly
      to analyte effective mobility. Using several well characterized analytes, we
      construct calibration curves relating effective mobility and carrier ampholyte
      displacement at two different leading electrolyte (LE) buffers. On the basis of
      these calibration curves, we demonstrate the extraction of fully ionized mobility
      and dissociation constant of 2-nitrophenol and 2,4,6-trichlorophenol from ITP
      experiments with fluorescent carrier ampholytes. This extraction is based on no a
      priori assumptions or knowledge of these two toxic chemicals. This technique
      allows simultaneous identification of multiple analytes by their physiochemical
      properties in a few minutes and with no sample preparation.

PMID- 20141173
TI  - Bioactive bromophycolides R-U from the Fijian red alga Callophycus serratus.
AB  - Four new bromophycolides, R-U (1-4), were isolated from the Fijian red alga
      Callophycus serratus and were identified by 1D and 2D NMR and mass spectroscopic
      analyses. These compounds expand the known structural variety of diterpene
      benzoate macrolides and exhibited modest cytotoxicity toward selected human
      cancer cell lines. Bromophycolide S (2) also showed submicromolar activity
      against the human malaria parasite Plasmodium falciparum.

PMID- 20141175
TI  - Toward solar fuels: photocatalytic conversion of carbon dioxide to hydrocarbons.
AB  - The past several decades have seen a significant rise in atmospheric carbon
      dioxide levels resulting from the combustion of hydrocarbon fuels. A solar energy
      based technology to recycle carbon dioxide into readily transportable hydrocarbon
      fuel (i.e., a solar fuel) would help reduce atmospheric CO2 levels and partly
      fulfill energy demands within the present hydrocarbon based fuel infrastructure.
      We review the present status of carbon dioxide conversion techniques, with
      particular attention to a recently developed photocatalytic process to convert
      carbon dioxide and water vapor into hydrocarbon fuels using sunlight.

PMID- 20141176
TI  - Three myths about water.

PMID- 20141177
TI  - Controllable construction of carbohydrate microarrays by site-directed grafting
      on self-organized porous films.
AB  - Carbohydrate-protein interactions are critical in many biological processes.
      However, the interactions between individual carbohydrates and proteins are often
      of low affinity and difficult to study. Recent development of carbohydrate
      microarrays provides an effective tool to explore the interaction. In this work,
      carbohydrate microarrays were controllably constructed by grafting of a
      carbohydrate-containing monomer on self-organized honeycomb-patterned films. The
      films were prepared from an amphiphilic block copolymer, poly(styrene-block-(2
      hydroxyethyl methacrylate)), by a breath figure method. Three-dimensional
      fluorescence results demonstrate that the hydroxyl groups aggregate mainly inside
      the pores, which afford a chance of site-directed surface modification. 2
      (2,3,4,6-Tetra-O-acetyl-beta-D-glucosyloxy)ethyl methacrylate was selectively
      grafted in the pores by a surface-initiated atom transfer radical polymerization.
      Characterization by attenuated total reflectance Fourier transform infrared
      spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy,
      atomic force microscopy, and contact angle measurements confirms the site
      directed growth of the glycopolymer chains. Further specific recognition of the
      carbohydrate microarrays to lectin (concanavalin A) leads to an organized
      microarray of protein, and hence this approach also opens a new route to
      fabricating other functional microarrays such as protein-patterned surfaces.

PMID- 20141178
TI  - Five-membered arsenic-sulfur-nitrogen heterocycles, RAs(S2N2) (R = Me, Et, (i)Pr,
      (t)Bu, Ph, Mes).
AB  - A series of 5-alkyl/aryl-1,3lambda(4)delta(2),2,4,5-dithiadiazarsoles
      RAs(S(2)N(2)) (R = Me, Et, (i)Pr, (t)Bu, Ph, Mes) were prepared by a ligand
      exchange between [(n)Bu(2)Sn(S(2)N(2))](2) and the corresponding
      organodihalogenoarsines RAsX(2) (X = Cl, I). All products were characterized by
      NMR, IR, and Raman spectroscopies and mass spectrometry. The crystal structures
      of the aryldithiadiazarsoles (R = Ph, Mes) were determined.

PMID- 20141179
TI  - First actinide complexes of the nitrogen-containing ligands dinitramide (N(NO2)2(
      )), 4,5-Dicyano-1,2,3-triazolate (C4N5(-)), and dicyanamide (N(CN)2(-)).
AB  - The syntheses and characterization of uranyl complexes of nitrogen-containing
      ligands are reported. For the first time, an actinide complex containing
      dinitramide ligands coordinated to the actinide center in
      UO(2)(N(NO(2))(2))(2)(OP(NMe(2))(3))(2) (1) has been isolated and structurally
      characterized. Using an excess of OP(NMe(2))(3), the dinitramide ligands were
      replaced by OP(NMe(2))(3) ligands resulting in the formation of the salt
      [UO(2)(OP(NMe(2))(3))(4)][N(NO(2))(2)](2) (2). Both complexes 1 and 2 were
      characterized using IR, Raman, as well as (1)H, (13)C, (14)N and (31)P{(1)H} NMR
      spectroscopy, in addition to C/H/N analysis. The structures of 1 and 2 were
      determined by single crystal X-ray diffraction. 1: monoclinic, P2(1)/n, a =
      12.5389(3), b = 7.9496(2), c = 15.8172(4) A, beta = 110.842(3) degrees , V =
      1473.48(6) A(3), Z = 2. 2: orthorhombic, Pbca, a = 14.5640(6), b = 15.3697(6), c
      = 45.7789(18) A, V = 10247.3(7) A(3), Z = 8. The related complex
      [UO(2)(N(CN)(2))(2)(OP(NMe(2))(3))(2)] (3) containing the dicyanamide ligand
      (N(CN)(2)(-)) coordinated to the U(VI) center was synthesized and characterized
      using IR, Raman, (1)H, (13)C and (31)P{(1)H} NMR spectroscopy. The structure of 3
      was determined using single crystal X-ray diffraction and revealed a dinuclear
      complex containing both terminal and bridging N(CN)(2)(-) ligands. 3: monoclinic,
      P2(1)/c, a = 15.5873(9), b = 14.2132(6), c = 13.2006(5) A, beta = 100.029(3)
      degrees, V = 2879.8(2) A(3), Z = 2. Finally, in this investigation of the
      coordination of relatively nitrogen-rich ligands to uranium centers, the
      synthesis, characterization, and isolation of the first U(VI) complex showing
      coordination of the triazolate ligand via a ring nitrogen atom is reported in
      UO(2)((NC)(2)C(2)N(3))(2)(OPPh(3))(3) (4). Complex 4 was characterized using IR,
      Raman, (1)H, (13)C and (31)P{(1)H} NMR spectroscopy. The solid state structure of
      4 was determined using single crystal X-ray diffraction. 4: monoclinic, P2(1)/n,
      a = 18.9970(2), b = 31.9500(3), c = 20.1133(2) A, beta = 111.4449(4) degrees, V =
      11362.69(19) A(3), Z = 8. To the best of our knowledge, compounds 1 and 2 are the
      first structurally characterized complexes where a dinitramide ligand is
      coordinated to an f-block center. Complex 3 is the first structurally
      characterized actinide dicyanamide complex and a rare example of a dinuclear
      uranyl complex showing a 12 membered U-N-C ring formed by bridging dicyanamide
      ligands between two uranyl centers. Finally, complex 4 is the first isolated and
      structurally characterized uranium complex containing a triazolate ligand
      coordinated to the U(VI) center. Complexes 3 and 4 are examples of uranyl
      complexes containing ligands coordinated via nitrogen atoms to the U(VI) center.
      Whereas the dinitramide ligand can coordinate via N or O atoms, in complex 1, the
      [N(NO(2))(2)](-) ligand acts as a bidentate chelate ligand, and only coordination
      via the oxygen atoms to the U(VI) center was observed in the crystalline state.

PMID- 20141180
TI  - Excited state localization and internuclear interactions in asymmetric
      ruthenium(II) and osmium(II) bpy/tpy based dinuclear compounds.
AB  - The synthesis of two asymmetric dinuclear complexes with the formula
      [M(bpy)(2)(bpt)Ru(tpy)Cl](2+), where M = Ru (1a), Os(2a); bpy = 2,2'-bipyridyl;
      Hbpt = 3,5-bis(pyridin-2-yl)1,2,4-triazole and tpy = 2,2',6',2''-terpyridine, is
      reported. The compounds obtained are characterized by mass spectrometry, (1)H
      NMR, UV/vis/NIR absorption, luminescence, and resonance Raman spectroscopy.
      Deuterium isotope labeling facilitates assignment of the (1)H NMR and resonance
      Raman spectra. The interaction between the two metal centers, mediated by the
      bridging 1,2,4-triazolato moiety in the mixed valent state, is assigned as type
      II based on the observation of metal to metal charge transfer absorption bands at
      7090 and 5990 cm(-1) for 1a and 2a, respectively. The extent of localization of
      the emissive excited state was determined by transient resonance Raman and
      emission spectroscopy. Both 1a and 2a show phosphorescence at the same
      wavelengths; however, whereas for compound 1a the emission is based on the
      Ru(tpy)Cl- center, for 2a the emissive state is localized on the Os(bpy)(2)-
      unit. This indicates that also in the excited state there is efficient
      interaction between the two metal centers.

PMID- 20141181
TI  - Simple and efficient synthesis of a Nd:LaAlO3 NIR nanophosphor from rare earth
      alkoxo-monoaluminates Ln2Al2(O(i)Pr)12((i)PrOH)2 single source precursors by
      Bradley reaction.
AB  - Nanoparticles of a Nd-doped LaAlO(3) perovskite can be obtained rapidly and with
      quantitative yield using the Bradley (ether elimination) treatment of a mixture
      of individual Ln(2)Al(2)(O(i)Pr)(12)((i)PrOH)(2), Ln = La, Nd, in acetophenone.
      The initially produced particles are poorly crystalline, but their crystallinity
      improves strongly on heating to 800 degrees C, which leads also to a controllable
      aggregation. The prepared nanoparticles are rather solution stable and can easily
      be surface-modified, which opens prospects for their use as phosphors in
      bioimaging applications. The precursors, bimetallic isopropoxides of rare earth
      elements and aluminum with a 1:1 composition, Ln(2)Al(2)(O(i)Pr)(12)((i)PrOH)(2),
      can be prepared with high yields via direct dissolution of metallic lanthanoids
      in a solution of aluminum isopropoxide in a toluene-isopropanol medium or through
      a short time reflux of "Ln(O(i)Pr)(3)" with 1 equiv of Al(O(i)Pr)(3) in toluene.
      In spite of good volatility and their proper composition, the
      Ln(2)Al(2)(O(i)Pr)(12)((i)PrOH)(2), Ln = La, Nd, do not act as single-source
      precursors in MOCVD, because of their quantitative transformation into
      LnAl(3)(O(i)Pr)(12) together with Ln(5)O(O(i)Pr)(13) on evaporation. These
      molecules are, however, present intact in solution according to variable
      temperature NMR studies, which permits application of them successfully as single
      source precursors in the synthesis of Ln:LaAlO(3) perovskite nanopowders with
      compositions thoroughly controlled through the conditions of the synthesis.
      Luminescent properties of the Nd:LaAlO(3) were examined and discussed in detail.
      The thermal population of the (4)F(5/2) and (2)H(9/2) states was found as a
      consequence of the grain size effect causing difficulties in heat dissipation.
      Moreover, luminescence behavior of the powder annealed at a lowest temperature
      shows well-defined short-range order.

PMID- 20141182
TI  - Cu-catalyzed arylation of phenols: synthesis of sterically hindered and
      heteroaryl diaryl ethers.
AB  - Cu-catalyzed O-arylation of phenols with aryl iodides and bromides can be
      performed under mild condition in DMSO/K(3)PO(4) with use of picolinic acid as
      the ligand for copper. This method tolerates a variety of functional groups and
      is effective in the synthesis of hindered diaryl ethers and heteroaryl ethers.

PMID- 20141184
TI  - Single molecule sensitive multivalent polyethylene glycol probes for RNA imaging.
AB  - The imaging of RNA in live cells presents a methodological challenge both in the
      mechanism by which the probes are delivered to the cell and in the sensitivity of
      the probe. Probes must be delivered to the correct cellular compartment and, once
      inside the cell, should bind to the target RNA rapidly and with enough
      sensitivity to detect small numbers of RNA molecules. Here, we report the
      characterization of a single-molecule sensitive, multivalent RNA imaging probe
      that utilizes an eight-armed poly(ethylene glycol) core. This probe allowed for
      the accurate imaging of the human respiratory syncytial virus (hRSV) genomic RNA
      when delivered into live cells using either reversible membrane permeabilization
      or TAT-peptide mediated membrane transduction. Neither reversible membrane
      permeabilization nor TAT mediated delivery proceeded through the endosomal
      pathway, and both delivery methods demonstrated fast binding kinetics of less
      than 10 min. Subcellular distributions of RNA were visualized in live cells, as
      well as RNA-protein colocalization, after fixation and immunostaining of the hRSV
      RNA binding protein N. 

PMID- 20141183
TI  - Electronic signatures of all four DNA nucleosides in a tunneling gap.
AB  - Nucleosides diffusing through a 2 nm electron-tunneling junction generate current
      spikes of sub-millisecond duration with a broad distribution of peak currents.
      This distribution narrows 10-fold when one of the electrodes is functionalized
      with a reagent that traps nucleosides in a specific orientation with hydrogen
      bonds. Functionalizing the second electrode reduces contact resistance to the
      nucleosides, allowing them to be identified via their peak currents according to
      deoxyadenosine > deoxycytidine > deoxyguanosine > thymidine, in agreement with
      the order predicted by a density functional calculation.

PMID- 20141185
TI  - Palladium-catalyzed direct cyanation of indoles with K(4)[Fe(CN)(6)].
AB  - Direct cyanation of indole derivatives has been achieved with nontoxic
      K(4)[Fe(CN)(6)] as cyanating agent through Pd-catalyzed C-H bond activation.

PMID- 20141186
TI  - Terrestrial carbon disturbance from mountaintop mining increases lifecycle
      emissions for clean coal.
AB  - The Southern Appalachian forest region of the U.S.--a region responsible for 23%
      of U.S. coal production--has 24 billion metric tons of high quality coal
      remaining of which mountaintop coal mining (MCM) will be the primary extraction
      method. Here we consider greenhouse gas emissions associated with MCM terrestrial
      disturbance in the life-cycle of coal energy production. We estimate disturbed
      forest carbon, including terrestrial soil and nonsoil carbon using published U.S.
      Environmental Protection Agency data of the forest floor removed and U.S.
      Department of Agriculture--Forest Service inventory data. We estimate the amount
      of previously buried geogenic organic carbon brought to the soil surface during
      MCM using published measurements of total organic carbon and carbon isotope data
      for reclaimed soils, soil organic matter and coal fragments. Contrary to
      conventional wisdom, the life-cycle emissions of coal production for MCM methods
      were found to be quite significant when considering the potential terrestrial
      source. Including terrestrial disturbance in coal life-cycle assessment indicates
      that indirect emissions are at least 7 and 70% of power plant emissions for
      conventional and CO(2) capture and sequestration power plants, respectively. To
      further constrain these estimates, we suggest that the fate of soil carbon and
      geogenic carbon at MCM sites be explored more widely.

PMID- 20141187
TI  - Syntheses, characterization, and photophysical properties of conjugated
      organometallic Pt-acetylide/Zn(II) porphyrin-containing oligomers.
AB  - Two conjugated organometallic oligomers of the type (-C[triple
      bond]CPt(L)(2)C[triple bond]C(ZnP)-)(n) and model compounds [PhC[triple
      bond]CPt(L)(2)C[triple bond]C(ZnP)C[triple bond]CPt(L)(2)C[triple bond]CPh] with
      L = tri(n-butyl)-phosphine and ZnP = zinc(II)(10,20-bis(Ar)porphyrine) (Ar =
      mesityl (Mes; P1 and M1) or 3,4,5-trihexadecyloxyphenyl (P2 and M2)) were
      synthesized and characterized ((1)H and (31)P NMR, HRMS, elemental analysis, IR,
      GPC, and TGA). GPC indicates that P1 and P2 exhibit respectively approximately 6
      and approximately 3 units with a polydispersity of 1.4. M1 was also characterized
      by X-ray crystallography. The Pt...Pt separation in M1 is 1.61 nm, which makes P1
      approximately 9.6 nm long. The spectral measurements show that the absorption and
      photoluminescence spectra of M1, M2, P1, and P2 are remarkably red-shifted. For
      example, the low energy Q-band is observed at 677 +/- 1 nm in comparison with
      their precursors HC[triple bond]C(ZnP)C[triple bond]CH, L1 and L2 (Ar = mesityl
      (Mes; L1) or 3,4,5-trihexadecyloxyphenyl (L2)), both at 298 and 77 K, for which
      the Q-band is observed at 622 nm. The photophysical parameters, fluorescence
      lifetimes (tau(F)), and quantum yields (Phi(F)) show a slight decrease by a
      factor of approximately 2 (at most 3) following the trend L1 approximately L2 >
      M1 approximately M2 > P1 approximately P2, a trend explained by a combination of
      the heavy atom effect and an increase in internal conversion rate due to the
      increase in oligomer dimension. This small variation of the photophysical data
      for materials of a few nm in dimension contrasts with the larger change in
      tau(P), phosphorescence lifetimes of the Pt-containing unit in the (
      C(6)H(4)C[triple bond]CPt(L)(2)C[triple bond]C-CC(6)H(4)(ZnP)-)(n) oligomers with
      n = 3, 6, and 9 reported earlier (Liu, L.; Fortin, D.; Harvey, P. D. Inorg. Chem.
      2009, 48, 5891-5900). In this later case, tau(P) decreased by steps of an order
      of magnitude as n increased from 3 to 6 to 9. This decrease was explained by a
      T(1) energy transfer from the Pt unit (donor) to MP (acceptor) in combination
      with an excitonic process (energy delocalization). Because of the full
      conjugation in P1 and P2, these oligomers behave as distinct molecules, and no
      energy transfer occurs. These properties make these materials suitable candidates
      for photocell applications.

PMID- 20141188
TI  - High resolution Raman and neutron investigation of Mg(BH4)2 in an extensive
      temperature range.
AB  - Raman spectra of Mg(BH(4))(2) have been measured in an extensive temperature
      range, from 15 to 473 K. Taking into account the high temperature conversion from
      the alpha to the beta phase, we have observed evident signatures of this phase
      transition and determined the Raman vibrational spectrum of each phase. The
      neutron scattering spectra of the beta phase sample were also recorded. The
      present experimental results have been compared to the density functional theory
      calculations available in the literature, and a substantial agreement has been
      found.

PMID- 20141189
TI  - Bond evolution in electron transfer: a time-resolved EXAFS study.
AB  - The photoinduced electron transfer reaction of [Co(III)(NH(3))(6)](3+) complex,
      after 266/267 nm excitation in the charge transfer band, has been studied by
      means of ultrafast EXAFS, optical transient spectroscopy, and quantum chemistry
      calculations. The Co-N bond length changes and the transient spectra and kinetics
      have been measured and in combination with DFT theoretical calculations are used
      to determine the photochemical mechanism of the Co(III) to Co(II) redox reaction.
      The data presented show that the Co-N bond length changes from the Co(III)-N 1.93
      A length to the 2.12 A Co(II)-N length within 2 ps and then remains constant for
      at least 100 ps. This strongly implies that intramolecular electron transfer from
      the ligand to cobalt occurs during the first 2 ps after excitation. Low quantum
      yield electron photodetachment from [Co(III)(NH(3))(6)](3+) complex has also been
      observed.

PMID- 20141190
TI  - Reaction of the C2H radical with 1-butyne (C4H6): low-temperature kinetics and
      isomer-specific product detection.
AB  - The rate coefficient for the reaction of the ethynyl radical (C(2)H) with 1
      butyne (H-C[triple bond]C-CH(2)-CH(3)) is measured in a pulsed Laval nozzle
      apparatus. Ethynyl radicals are formed by laser photolysis of acetylene
      (C(2)H(2)) at 193 nm and detected via chemiluminescence (C(2)H + O(2) --> CH
      (A(2)Delta) + CO(2)). The rate coefficients are measured over the temperature
      range of 74-295 K. The C(2)H + 1-butyne reaction exhibits no barrier and occurs
      with rate constants close to the collision limit. The temperature-dependent rate
      coefficients can be fit within experimental uncertainties by the expression k =
      (2.4 +/- 0.5) x 10(-10)(T/295 K)(-(0.04+/-0.03)) cm(3) molecule(-1) s(-1).
      Reaction products are detected at room temperature (295 K) and 533 Pa using a
      multiplexed photoionization mass spectrometer (MPIMS) coupled to the tunable
      vacuum ultraviolet synchrotron radiation from the Advanced Light Source at the
      Lawrence Berkeley National Laboratory. Two product channels are identified for
      this reaction: m/z = 64 (C(5)H(4)) and m/z = 78 (C(6)H(6)) corresponding to the
      CH(3)-loss and H-loss channels, respectively. Photoionization efficiency (PIE)
      curves are used to analyze the isomeric composition of both product channels. The
      C(5)H(4) products are found to be exclusively linear isomers composed of
      ethynylallene and methyldiacetylene in a 4:1 ratio. In contrast, the C(6)H(6)
      product channel includes two cyclic isomers, fulvene 18(+/-5)% and 3,4
      dimethylenecyclobut-1-ene (DMCB) 32(+/-8)%, as well as three linear isomers, 2
      ethynyl-1,3-butadiene 8(+/-5)%, 3,4-hexadiene-1-yne 28(+/-8)%, and 1,3-hexadiyne
      14(+/-5)%. Within experimental uncertainties, we do not see appreciable amounts
      of benzene and an upper limit of 10% is estimated. Diacetylene (C(4)H(2))
      formation via the C(2)H(5)-loss channel is also thermodynamically possible but
      cannot be observed due to experimental limitations. The implications of these
      results for modeling of planetary atmospheres, especially of Saturn's largest
      moon Titan and the relationships to combustion reactions, are discussed.

PMID- 20141191
TI  - Corner turning and shock desensitization experiments plus numerical modeling of
      detonation waves in the triaminotrinitrobenzene based explosive LX-17.
AB  - Five new experiments are reported that tested both detonation wave corner turning
      and shock desensitization properties of the triaminotrinitrobenzene (TATB) based
      plastic bonded explosive (PBX) LX-17. These experiments used small
      pentaerythritol tetranitrate (PETN) charges to initiate hemispherical ultrafine
      TATB (UF TATB) boosters, which then initiated LX-17 hemispherical detonations.
      The UF TATB boosters were placed under steel shadow plates embedded in the LX-17
      cylindrical charges, which were covered by thin aluminum plates. The LX-17
      detonation waves propagated outward until they reached the aluminum plates, which
      were instrumented with photonic Doppler velocimetry probes to measure their axial
      free surface velocities. X-ray radiographs and framing camera images were taken
      at various times. The LX-17 detonations propagated around the two corners of the
      steel shadow plates and into thin LX-17 layers placed between the steel and the
      top aluminum plates. The detonation waves were met there by weak diverging shocks
      that propagated through the steel plates and imparted 1-2 GPa pressures to these
      unreacted LX-17 layers. These weak shock waves compressed and desensitized the
      unreacted LX-17, resulting in failures of the LX-17 detonation waves. The
      hydrodynamics of double corner turning and shock desensitization in the five
      experiments were modeled in two dimensions using the Ignition and Growth LX-17
      detonation reactive flow model. The calculated arrival times and axial free
      surface velocity histories of the top aluminum plates were in excellent agreement
      with the experimental measurements.

PMID- 20141192
TI  - Rotation of methyl radicals in molecular solids.
AB  - Electron spin resonance (ESR) measurements were carried out to study the rotation
      of methyl radicals (CH(3)) in solid carbon monoxide, carbon dioxide, and nitrogen
      matrices. The radicals were produced by dissociating methane by plasma bursts
      generated by a focused 193 nm ArF excimer laser radiation during the gas
      condensation on the substrate. The ESR spectra exhibit anisotropic features that
      persist over the temperature range examined, and in most cases this indicates a
      restriction of rotation about the C(2) symmetry axis. A nonrotating CH(3) was
      also observed in a CO(2) matrix. The intensity ratio between the symmetric (A)
      and antisymmetric (E) nuclear spin states was recorded as a function of
      temperature for each molecular matrix. The rotational energy levels are modified
      from their gas phase structure with increasing crystal field strength. An
      anomalous situation was observed where the A/E ratio extended below the high
      temperature limit of 1/2.

PMID- 20141193
TI  - Infrared matrix isolation and theoretical study of the initial intermediates in
      the reaction of ozone with cis-2-butene.
AB  - Matrix isolation studies combined with infrared spectroscopy of the twin jet
      codeposition of ozone and cis-2-butene into argon matrices have led to the first
      observation of several early intermediates in this ozonolysis reaction.
      Specifically, evidence is presented for the formation and identification of the
      long sought-after Criegee intermediate, as well as confirming evidence for
      earlier reports of the primary and secondary ozonides. These species were
      observed after initial twin jet deposition, and grew upon annealing to 35 K.
      Extensive isotopic labeling ((18)O and (16,18)O mixtures) experiments provided
      important supporting data. Detailed theoretical calculations at the B3LYP/6
      311++G(d,2p) level were carried out as well to augment the experimental work.
      Merged jet (flow reactor) experiments followed by cryogenic trapping in solid
      argon led to the formation of "late", stable oxidation products. Photochemical
      reactions of ozone with cis-2-butene was studied as well, as was the
      photochemical behavior of the primary and secondary ozonides.

PMID- 20141194
TI  - Bond dissociation energies of organophosphorus compounds: an assessment of
      contemporary ab initio procedures.
AB  - Thermodynamic properties of phosphorus-containing compounds were investigated
      using high-level ab initio computations. An extended set of contemporary density
      functional theory (DFT) procedures was assessed for their ability to accurately
      predict bond dissociation energies of a set of phosphoranyl radicals. The results
      of meta- and double-hybrids as well as more recent methods, in particular M05,
      M05-2X, M06, and M06-2X, were compared with benchmark G3(MP2)-RAD values.
      Standard heats of formation, entropies, and heat capacities of a set of ten
      organophosphorus compounds were determined and the low-cost BMK functional was
      found to provide results consistent with available experimental data. In
      addition, bond dissociation enthalpies (BDEs) were computed using the BMK, M05
      2X, and SCS-ROMP2 procedure. The three methods give the same stability trend. The
      BDEs of the phosphorus(III) molecules were found to be lower than their
      phosphorus(V) counterparts. Overall, the following ordering is found: BDE(P-OPh)
      < BDE(P-CH(3)) < BDE(P-Ph) < BDE(P-OCH(3)).

PMID- 20141196
TI  - Selective apoptotic killing of solid and hematologic tumor cells by bombesin
      targeted delivery of mitochondria-disrupting peptides.
AB  - Tumor-homing peptides are attractive tools for tumor imaging and targeted therapy
      due to their ability to specifically bind and enter tumor cells and masses.
      Bombesin and its analogues show promise for the targeted delivery of radioactive
      and chemotherapeutic agents to a wide variety of solid tumors. Here, we describe
      the bombesin-targeted delivery of toxic peptides to solid tumor cells and
      leukemia cells. We found that bombesin specifically bound to solid tumor cells
      and leukemia cells with similar affinity. Conjugation to bombesin significantly
      (5-15 times) enhanced the cytotoxicity of three mitochondria-disrupting peptides
      (KLA, B27, and B28) in solid tumor cells and leukemia cells through improvement
      of their binding affinity. The bombesin-directed peptides (KB, BB27, and BB28)
      contained the same bombesin leader sequence but had different mitochondria
      disrupting peptides, which selectively induced caspase-dependent apoptosis in
      solid tumor cells and leukemia cell lines. The IC50 values of these peptides
      (BB27, 3-5 micromol/L; BB28, 4-6 micromol/L) for solid tumor cells and leukemia
      cells are approximately 5-10 times lower than the IC50 values for normal cells.
      BB27 and BB28 also displayed cytotoxicity in primary leukemia cells from patients
      (n = 4) with acute myeloid leukemia. Intratumoral (10 mg/kg) and intraperitoneal
      (20 mg/kg) injection of BB27 and BB28 exerted substantial inhibition on K562
      tumor xenograft growth without obvious systematic toxicity. Our results suggest
      that the bombesin-directed mitochondria-disrupting peptides BB27 and BB28 might
      be used as therapeutic agents not only for solid tumors but also for hematologic
      tumors.

PMID- 20141195
TI  - Chemical biology strategy reveals pathway-selective inhibitor of NF-kappaB
      activation induced by protein kinase C.
AB  - Dysregulation of NF-kappaB activity contributes to many autoimmune and
      inflammatory diseases. At least nine pathways for NF-kappaB activation have been
      identified, most of which converge on the IkappaB kinases (IKKs). Although IKKs
      represent logical targets for potential drug discovery, chemical inhibitors of
      IKKs suppress all known NF-kappaB activation pathways and thus lack the
      selectivity required for safe use. A unique NF-kappaB activation pathway is
      initiated by protein kinase C (PKC) that is stimulated by antigen receptors and
      many growth factor receptors. Using a cell-based high-throughput screening (HTS)
      assay and chemical biology strategy, we identified a 2-aminobenzimidazole
      compound, CID-2858522, which selectively inhibits the NF-kappaB pathway induced
      by PKC, operating downstream of PKC but upstream of IKKbeta, without inhibiting
      other NF-kappaB activation pathways. In human B cells stimulated through surface
      immunoglobulin, CID-2858522 inhibited NF-kappaB DNA-binding activity and
      expression of endogenous NF-kappaB-dependent target gene, TRAF1. Altogether, as a
      selective chemical inhibitor of the NF-kappaB pathway induced by PKC, CID-2858522
      serves as a powerful research tool and may reveal new paths toward
      therapeutically useful NF-kappaB inhibitors.

PMID- 20141197
TI  - Chemical models of peptide formation in translation.
AB  - Ribosomal incorporations of N-alkyl amino acids including proline are slower than
      incorporations of non-N-alkyl l-amino acids. The chemical reactivity hypothesis
      proposes that these results and the exclusion of nonproline N-alkyl amino acids
      from the genetic code are explained by intrinsic chemical reactivities of the
      amino acid nucleophiles. However, there is little data on the reactivities
      relevant to physiological conditions. Here, we use nonenzymatic, aqueous-based,
      buffered reactions with formylmethionine-N-hydroxysuccinimide ester to model 11
      amino acid nucleophiles in dipeptide formation. The relative rates in the
      nonenzymatic and translation systems correlate well, supporting the chemical
      reactivity hypothesis and arguing that peptide bond formation, not accommodation,
      is rate limiting for natural Pro-tRNA(Pro) isoacceptors. The effects of N
      substitution sterics, side chain sterics, induction, and pK(a) were evaluated in
      the chemical model. The dominant factor affecting relative rates was found to be
      N-substitution sterics.

PMID- 20141198
TI  - Sustained rolling of microparticles in shear flow over an electrostatically
      patchy surface.
AB  - This paper explores the particle-level dynamics involved in the capture of gently
      flowing microparticles on adhesive planar surfaces, governed by electrostatic
      interactions. The work focuses on conditions which produce sustained
      microparticle rolling, useful for the development of microfluidic devices which
      steer analyte particles and cells for manipulation and separation. In the regime
      where particle-surface interactions dominate particle-particle interactions,
      capture of individual negative silica microspheres, for thousands of
      microspheres, is studied on three model surfaces: negative silica, a flat
      polycation layer adsorbed on silica producing a strong positive charge, and an
      electrostatically patchy surface containing 6% areal coverage of flat 10 nm
      polycation coils. The patchy surface possesses a net negative charge close to
      that of bare silica. On the patchy surface, sustained rolling is observed for a
      substantial population of 1 microm silica particles, the ones which happened to
      diffuse close to the surface. Here, the velocity is near 2 microm/s (for a wall
      shear of 22 s(-1).) Run lengths for particle rolling exceed several hundred
      micrometers (usually exceeding the length of the microscopic field of view), with
      more particles escaping diffusively from the interface than permanently
      arresting. By contrast, firm particle arrest, with very few instances of rolling
      and a short run length when rolling did occur, was observed on the fully cationic
      surface. On the bare silica surface, a small rolling population was observed;
      however, the average run length was shorter than on the patchy surface. This
      study demonstrated how a patchy surface that produces adhesion through localized
      attractions can facilitate rolling in a shear field. The physicochemical
      heterogeneity acts like a surface roughness or a rapidly binding ligand-receptor
      pair, transferring stress and imparting torque across the interface.

PMID- 20141199
TI  - Thermoresponsive vesicular morphologies obtained by self-assemblies of hybrid
      oligosaccharide-block-poly(N-isopropylacrylamide) copolymer systems.
AB  - This work discusses the self-assembly properties of thermoresponsive hybrid
      oligosaccharide-block-poly(N-isopropylacrylamide) copolymer systems:
      maltoheptaose-block-poly(N-isopropylacrylamide) (Mal(7)-b-PNIPAM(n)) copolymers.
      Those systems at different molar masses and volume fractions were synthesized
      using Cu(I)-catalyzed 1,3-dipolar azide/alkyne cycloaddition, so-called "click"
      chemistry, between an alkynyl-functionalized maltoheptaose (1) and poly(N
      isopropylacrylamide) having a terminal azido group (N(3)-PNIPAM(n)) prepared by
      atom transfer radical polymerization (ATRP). While the cloud point (T(cp)) of the
      N(3)-PNIPAM(n) ranged from 36.4 to 51.5 degrees C depending on the degree of
      polymerization, those obtained of the diblock copolymers ranged from 39.4 to 73.9
      degrees C. The self-assembly of such systems is favored due to the hydrophobicity
      of the PNIPAM in water above the T(cp). While the N(3)-PNIPAM(n) present
      polydisperse globular shape with a mean diameter of 500 nm, well-defined
      vesicular morphologies with an approximate diameter of 300 nm are obtained in
      diblock copolymer systems. These results were obtained and confirmed using static
      and dynamic light scattering as well as imaging techniques such as transmission
      electron microscope experiments.

PMID- 20141200
TI  - Contact angle assessment of hydrophobic silica nanoparticles related to the
      mechanisms of dry water formation.
AB  - Dry water is a very convenient way of encapsulating a high amount of aqueous
      solutions in a powder form made of hydrophobic silica nanoparticles. It was
      demonstrated in previous studies that both solid and liquid interfacial
      properties influence the quality of the final product resulting occasionally in
      mousse formation. To explain this behavior, contact angles of silica
      nanoparticles have been measured for water and water/ethanol solution by means of
      liquid intrusion experiments. It was found that the quality of the final product
      correlates with the contact angle, i.e., contact angle close to 105 degrees leads
      to mousse formation whereas a slightly higher value of approximately 118 degrees
      allows dry water formation. The proposed explanation was based on the energy of
      immersion and adhesion defined as the energy needed for a spherical particle to
      respectively penetrate into the liquid or attach at the liquid/air interface.
      Significantly lower energy of immersion calculated for lower contact angle might
      account for particle penetration into the liquid phase during processing, leading
      to continuous network aggregation, air entrapment, and finally mousse formation.

PMID- 20141202
TI  - Fabrication of artificial opals by electric-field-assisted vertical deposition.
AB  - We present a new technique for large-scale fabrication of colloidal crystals with
      controllable quality and thickness. The method is based on vertical deposition in
      the presence of a DC electric field normal to the conducting substrate. The
      crystal structure and quality are quantitatively characterized by microradian X
      ray diffraction, scanning electron microscopy, and optical reflectometry.
      Attraction between the charged colloidal spheres and the substrate promotes
      growth of thicker crystalline films, while the best-quality crystals are formed
      in the presence of repulsion. Highly ordered thick crystalline layers with a
      small amount of stacking faults and a low mosaic spread can be obtained by
      optimizing the growth conditions.

PMID- 20141201
TI  - Coordination and reduction processes in the synthesis of dendrimer-encapsulated
      Pt nanoparticles.
AB  - We synthesized Pt nanoparticles encapsulated in poly(amidoamine) (PAMAM)
      dendrimers by Pt(2+) coordination and subsequent reduction by NaBH(4). To
      optimize the experimental conditions for the Pt nanoparticle synthesis, we
      systematically examined the effects of pH, temperature, coordination time, and
      surface functional groups of the dendrimers on coordination and NaBH(4) reduction
      by UV-vis spectroscopy and transmission electron microscopy (TEM) measurements.
      We used generation-4 dendrimers (hydroxyl-terminated PAMAM dendrimers; G4-OH) and
      generation-4.5 dendrimers (carboxyl-terminated PAMAM dendrimers; G4.5-COO(-)).
      According to our results, dendrimer-encapsulated Pt nanoparticles with a narrow
      size distribution were obtained at high Pt(2+) coordination ratios (alpha), while
      nonencapsulated Pt nanoparticles were formed at low alpha values. To enhance
      alpha, it was necessary to use a neutral G4-OH solution or an acidic G4.5-COO(-)
      solution. Temperature had a marked effect on the coordination rate, with an
      increase in the temperature from room temperature to 50 degrees C, and the
      coordination time decreased from 10 days to 1-2 days.

PMID- 20141203
TI  - Adsorption layer characteristics of mixed SDS/C(n)EO(m) solutions. 3. Dynamics of
      adsorption and surface dilational rheology of micellar solutions.
AB  - The dynamic surface tensions of mixed SDS/C(12)EO(5) and SDS/C(14)EO(8) micellar
      solutions measured over a wide time range (0.1 ms to 10,000 s) at various mixing
      ratios are described satisfactorily by a theoretical model for the kinetics of
      adsorption of surfactant mixtures using the surfactant adsorption parameters
      obtained for premicellar mixed solutions. Additional relations used for the
      description of the adsorption kinetics from micellar solutions were expressions
      of the effective diffusion coefficient of monomers accounting for the
      disintegration of micelles. The modeled dynamic surface tensions agree well with
      the experimental data for all studied surfactant mixtures. The rheological
      behavior of the same mixtures--the dependencies of the viscoelasticity modulus
      and phase angle--were studied by using the bubble profile method at harmonic
      bubble surface area oscillations. The theoretical approach employed for data
      analysis was the same as for the dynamic surface tension behavior. Again,
      satisfactory agreement between the experimental data and theoretical calculations
      of the dilational rheological parameters was found.

PMID- 20141204
TI  - Structure and rheology of a self-standing nanoemulsion.
AB  - A stable nanoemulsion consisting of nanometer-sized oil droplets in water having
      a self-standing capability was prepared by high-pressure emulsification. The
      nanoemulsion does not flow and has a yield stress. This nonfluidity is ascribed
      to the crystal-like lattice structure of nanodroplets. The lattice structure was
      observed by transmission electron microscopy of a freeze-fractured surface of the
      specimen. Small-angle neutron scattering (SANS) revealed the presence of an
      ordered structure in addition to spherical domains with a radius of 17 nm. This
      long-range order is, in principle, due to electrostatic repulsive interaction
      between charged nanodroplets. Dynamic light scattering (DLS) showed two
      relaxation modes, one for the collective motion of the lattice and the other for
      the translational diffusion of the nanodroplets. Dilution of the nanoemulsion
      resulted in a transition from a crystal-like structure to a typical colloidal
      solution.

PMID- 20141205
TI  - Colloidal gas-liquid condensation of polystyrene latex particles with
      intermediate kappa a values (5 to 160, a >> kappa(-1)).
AB  - Polystyrene latex particles showed gas-liquid condensation under the conditions
      of large particle radius (a >> kappa(-1)) and intermediate kappa a, where kappa
      is the Debye-Huckel parameter and a is the particle radius. The particles were
      dissolved in deionized water containing ethanol from 0 to 77 vol %, settled to
      the bottom of the glass plate within 1 h, and then laterally moved toward the
      center of a cell over a 20 h period in reaching a state of equilibrium
      condensation. All of the suspensions that were 1 and 3 microm in diameter and
      0.01-0.20 vol % in concentration realized similar gas-liquid condensation with
      clear gas-liquid boundaries. In 50 vol % ethanol solvent, additional ethanol was
      added to enhance the sedimentation force so as to restrict the particles in a
      monoparticle layer thickness. The coexistence of gas-liquid-solid (crystalline
      solid) was microscopically recognized from the periphery to the center of the
      condensates. A phase diagram of the gas-liquid condensation was created as a
      function of KCl concentration at a particle diameter of 3 microm, 0.10 vol %
      concentration, and 50:50 water/ethanol solvent at room temperature. The
      miscibility gap was observed in the concentration range from 1 to 250 microM.
      There was an upper limit of salt concentration where the phase separation
      disappeared, showing nearly critical behavior of macroscopic density fluctuation
      from 250 microM to 1 mM. These results add new experimental evidence to the
      existence of colloidal gas-liquid condensation and specify conditions of like
      charge attraction between particles.

PMID- 20141206
TI  - Adsorption of anionic nanosheets from their dilute colloidal suspensions onto gas
      liquid interfaces with and without a Langmuir film of cationic surfactant.
AB  - The adsorption of [(Ca(2)Nb(3)O(10))(-)](n) (CNO) polyanionic nanosheets from
      their dilute colloidal suspensions onto gas-liquid interfaces with and without a
      cationic [N(CH(3))(2)(C(18)H(37))(2)](+) (DOA) surfactant film has been
      experimentally investigated. Our concern has been focused particularly on their
      dynamical aspects, which can be observed owing to the long specific time of the
      adsorption. The theoretical framework of the Langmuir adsorption model has
      enabled a quantitative analysis of the observed data, and that analysis has
      indicated that the presence of a positively charged Langmuir film enhances the
      ratio of the adsorption and desorption rate constants by approximately 30 times.
      Furthermore, the experimental results have shown that a "balanced" hybrid
      Langmuir film, in which both organic and inorganic constituents are densely
      packed, can be prepared.

PMID- 20141207
TI  - Bicellar mixtures containing pluronic F68: morphology and lateral diffusion from
      combined SANS and PFG NMR studies.
AB  - Small angle neutron scattering (SANS) and pulsed field gradient (PFG) nuclear
      magnetic resonance (NMR) diffusion measurements were applied to examine
      morphology and diffusion in dimyristoyl- plus dihexanoyl-phosphatidylcholine
      bicellar mixtures, either neutral or negatively charged, incorporating a Pluronic
      triblock copolymer (F68). Negatively charged bicellar mixtures, doped with
      dimyristoylphosphatidylglycerol (DMPG), exhibited SANS profiles consistent with a
      perforated lamellar morphology for the magnetically alignable phase.
      Correspondingly, F68 diffusion in this magnetically aligned phase was normal
      Gaussian, in that the mean square displacements increased linearly with the
      experimental diffusion time, with a lateral diffusion coefficient of 1.9 x 10(
      11) m(2) s(-1) consistent with a lipid bilayer inserted configuration. Neutral
      bicellar mixtures, that is, lacking DMPG, in contrast, displayed SANS profiles
      characteristic of ribbons arranged in such a fashion as to produce extended
      lamellae. Within the lamellae, the ribbons exhibited an in-plane periodicity
      (interribbon) of between 120 and 140 A. Correspondingly, F68 diffusion was non
      Gaussian, exhibiting a square root diffusion time dependence of the mean square
      displacement indicative of one-dimensional curvilinear diffusion. The presence or
      absence of DMPG, rather than of F68, dictated the ribbon versus lamellar
      morphology, with F68 reflecting this difference via its lateral diffusion
      behavior. Although ribbons have been reported previously, this is the first study
      to show that they aggregate, most likely into extended lamellar sheets, and
      eventually fold into multilamellar vesicles.

PMID- 20141208
TI  - Polyelectrolyte-mediated assembly of multiwalled carbon nanotubes on living yeast
      cells.
AB  - Here we report the three-dimensional assembly of carbon nanotubes on the
      polyelectrolyte-coated living Saccharomyces cerevisiae cells using the
      polyelectrolyte-mediated layer-by-layer approach. Synthetic polyelectrolytes
      poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) were layer-by
      layer deposited on the surfaces of the yeast cells followed by the deposition of
      water-soluble oxidized multiwalled carbon nanotubes (MWNTs) and an additional
      outermost polyelectrolyte bilayer. This resulted in the fabrication of
      polyelectrolyte/nanotubes composite coatings on the cell walls of the yeast
      cells, which could be clearly seen using the conventional optical microscopy.
      Transmission and scanning electron microscopy was applied to further investigate
      the composite coatings. Viability of the encapsulated cells was confirmed using
      the intercellular esterase activity test. Finally, electrochemical studies using
      voltammetry and electrochemical impedance measurements were performed, indicating
      that the composite polyelectrolytes/MWNTs coatings sufficiently affect the
      electron mediation between the encapsulated yeast cells and the artificial
      electron acceptor, making it possible to distinguish between living and dead
      cells. The technique described here may find potential application in the
      development of microelectronic devices, core-shell and hollow composite
      microparticles, and electrochemical cell-based biosensors.

PMID- 20141209
TI  - "Click" grafting of high loading of polymers and monosaccharides on surface of
      ordered mesoporous silica.
AB  - The azide-alkyne cycloaddition "click" reaction was used to covalently bond high
      loadings of polymers and monosaccharides to the surface of an ordered mesoporous
      silica. The functionalization process was followed using thermogravimetry, gas
      adsorption, small-angle X-ray scattering, and infrared spectroscopy. Large-pore
      SBA-15 silica with cylindrical mesopores of diameter approximately 15 nm was
      synthesized using triisopropylbenzene as a micelle expander. The surface of the
      silica was modified with aminopropyl groups that were converted to propargyl
      bearing groups through a reaction with 4-pentynoyl chloride. Thus prepared
      "clickable" pores were reacted with azide-functionalized poly(methyl
      methacrylate) (PMMA) and oligo(ethylene glycol) as well as protected and
      deprotected D-galactose. The new "grafting to" procedure allowed us to introduce
      uniform polymer films of thickness up to about 2 nm without any appreciable pore
      blocking, even for the polymer loading as high as 25 wt %. Uniform layers of
      monosaccharides with loadings up to 20 wt % were also obtained with remarkable
      grafting efficiency. No change in the periodic structure of the silica support
      was observed throughout the grafting process. These results demonstrate that the
      "click" reaction is a powerful approach to ordered mesoporous silicas with
      accessible pores functionalized with high loadings of various macromolecules and
      biomolecules.

PMID- 20141210
TI  - Langmuir and Langmuir-Blodgett films of bidisperse silica nanoparticles.
AB  - We present the studies on the structure and optical properties of bidisperse
      Stober silica nanoparticulate Langmuir films prepared at the air/water interface
      in a Wilhelmy film balance and transferred onto glass slides using the Langmuir
      Blodgett technique. Three different compositions (covered area ratios: 4:1; 1:1,
      and 1:4) of two bidisperse systems were used in the experiments. Bidisperse
      samples (B1 and B2) were prepared by mixing the appropriate amount of
      monodisperse sols of particles with 61 and 100 nm diameters (B1) and those with
      37 and 100 nm diameters (B2). By surface pressure-area isotherms and
      (transmission and scanning) electron microscopy images we provide information
      about the structure of the films. Optical properties of the supported films were
      measured with UV-vis spectroscopy and the transmittance spectra were evaluated in
      terms of an optical model which allows monotonous in-depth variation of the
      refractive index across the film. (1) We have found that the refractive index
      decreased from the substrate-layer interface toward the air-layer interface when
      the smaller particles were in majority, and increased otherwise. That would
      suggest that the smaller particles of each bidisperse system can be positioned at
      the air side of the film if they are in minority in the sample and they can be
      situated on the substrate if they are in majority. The scanning electron
      microscope images of bidisperse films supported the in-depth film structure
      suggested by optical studies.

PMID- 20141211
TI  - One-pot procedure to synthesize high surface area alumina nanofibers using
      supercritical carbon dioxide.
AB  - For the first time, high surface area nanofibers were synthesized using aluminum
      isopropoxide monomer with acetic acid as the polycondensation agent in the green
      solvent, supercritical carbon dioxide (scCO(2)). It was found that the synthesis
      temperature, pressure, concentration, and acid/alkoxide ratio had a large effect
      on fiber formation. By optimizing the experimental conditions at 80 degrees C and
      6000 psi of scCO(2) using aluminum isopropoxide at a concentration of 0.3 mmol/mL
      and acid/alkoxide ratio of 10, alumina nanofibers were formed ranging from 11 to
      22 nm in diameter and 500 to 1000 nm in length, and with surface areas up to 580
      m(2)/g. Lower temperatures gave irregular shaped nanoparticles, while a lower
      acid/alkoxide ratio (5:1) resulted in the formation of low surface area alumina
      bars. Increasing pressure led to better separation of the nanofibers and higher
      surface areas. In addition to the synthesis conditions, the influence of
      calcination temperature on the structural, textural, and morphological properties
      of the materials was examined using various physicochemical techniques including
      electron microscopy, TGA/DTA, powder XRD, FTIR, XPS, and nitrogen
      adsorption/desorption analysis. The long fibers with high aspect ratios were
      found to be thermally stable even after calcining at up to 1050 degrees C. The
      mechanism of fiber formation in scCO(2) is proposed based on a
      [Al(OH)(CH(3)CO(2))(2)](n) polycondensate backbone.

PMID- 20141212
TI  - Shape-dependent antibacterial activities of Ag2O polyhedral particles.
AB  - Ag(2)O particles with different polyhedral shapes including octahedron, truncated
      octahedron, and cube were successfully synthesized by a simple wet-chemical
      method using silver nitrate, ammonia, and sodium hydroxide as raw materials at
      room temperature. Simply by tuning the concentration of starting materials, the
      shape of Ag(2)O particles evolved from octahedron to cube, and the size gradually
      decreased from 1-2 microm to 400-700 nm. As examples for promising applications,
      the antibacterial activities of the as-prepared Ag(2)O polyhedral particles were
      preliminarily studied. It has been found the antibacterial activity of Ag(2)O
      particles against E. coli depends on the shape of Ag(2)O particles, demonstrating
      that the surface structure of Ag(2)O particles affects the antibacterial
      activity.

PMID- 20141213
TI  - Aggregation behavior of graft copolymer with rigid backbone.
AB  - The self-assembly behavior of poly(gamma-benzyl-L-glutamate)-graft-poly(ethylene
      glycol) rod-coil graft copolymers in aqueous solution was investigated. With
      tetrahydrofuran (THF) as initial solvent, vesicles were observed for the graft
      copolymers with lower degree of grafting. When the degree of grafting increases,
      the aggregate morphology transforms from vesicles to spindle-like micelles then
      to spherical micelles. When N,N'-dimethylformamide (DMF) is introduced into the
      initial solvent, the vesicles transform to spindles. Increasing DMF volume
      fraction leads to a spindle to connected-spindle transition. On the basis of the
      experimental results, the mechanism of the morphological transition of the rod
      coil graft copolymer is suggested.

PMID- 20141214
TI  - A multifunctional biocide/sporocide and photocatalyst based on titanium dioxide
      (TiO2) codoped with silver, carbon, and sulfur.
AB  - Composite nanostructured samples of Ag (0.5-20%)/(C, S)-TiO(2) were synthesized
      and characterized by EDX, XRD, FT-IR, UV-vis, BET, XPS, and zeta potential
      measurements. Photocatalytic and biocidal tests revealed that the amount of the
      codoped silver (Ag(+)) in (C, S)-TiO(2) played a crucial, distinctive role in the
      photodegradation of gas-phase acetaldehyde as well as in the inactivation of
      Escherichia coli cells and Bacillus subtilis spores. Very interestingly, Ag/(C,
      S)-TiO(2) nanoparticles (crystallite size <10 nm) have shown very strong
      antimicrobial properties without light activation against both E. coli (log kill
      >8) and B. subtilis spores (log kill >5) for 30 min exposures, compared with P25
      TiO(2). Thus, for the first time, we have demonstrated that titanium dioxide (an
      environmentally friendly photocatalyst) codoped with silver, carbon, and sulfur
      can serve as a multifunctional generic biocide as well as a visible light
      activated photocatalyst.

PMID- 20141215
TI  - Formation and photocatalytic application of ZnO nanotubes using aqueous solution.
AB  - Vertically aligned ZnO nanotubes were prepared by etching ZnO rod arrays in
      aqueous solution, which were previously developed by chemical bath deposition
      method. The morphological, structural, photoluminescence, as well as
      photocatalytic properties of the ZnO nanotubes were examined with respect to the
      pH values of chemical bath solution. The morphology of the products was found to
      be sensitive to the pH values and chemical bath temperatures. The nanotubes
      synthesized at a low pH value (5.82) exhibited a strong UV emission and a weak
      defect-related visible emission. The highest photocatalytic efficiency was also
      observed at pH = 5.82. The possible mechanism for the difference of
      photocatalytic efficiency was discussed.

PMID- 20141216
TI  - Impregnation of tubular self-assemblies into dextran hydrogels.
AB  - Amine groups are the building units of proteins. The incorporation of amine
      groups into polyethylene glycol diacrylate (PEGDA) hydrogel through dextran-allyl
      isocyanate-ethylamine (Dex-AE) enhances sustained protein release by introducing
      effective interactions. To investigate such an interaction effect and to improve
      protein release, we impregnated self-assembled tubular structures from dextran
      bromoethylamine (Dex-BH) and dextran-chloroacetic acid (Dex-CA) into Dex-AE/PEGDA
      hydrogel. The morphology data obtained from scanning electron microscopy (SEM)
      reveal that pure PEGDA hydrogel had no effect on the distribution of the self
      assembled tubules; the introduction of Dex-AE brought about the dispersion of
      these tubules, and an increase in Dex-AE content led to more evenly distributed
      structures. Moreover, the implantation of the self-assembled tubules had no
      distinct effect on the swelling capacity of the hybrid self-assembly embedded
      hydrogels. The in vitro albumin release study was carried out in a pH 7.4 buffer
      solution; the results show that the implantation of the self-assembly into the
      hydrogels reduced the burst release and prolonged the protein release time. These
      findings demonstrate that the impregnation of tubular self-assembly into hydrogel
      makes the hybrid hydrogel an excellent protein delivery system.

PMID- 20141217
TI  - Pt-encapsulated Pd-Co nanoalloy electrocatalysts for oxygen reduction reaction in
      fuel cells.
AB  - Pt-encapsulated Pd(x)Co(100-x) nanoalloy electrocatalysts supported on carbon
      have been synthesized by a rapid microwave-assisted solvothermal (MW-ST) method
      within 15 min at as low as 300 degrees C. Subsequently, the samples have been
      heat treated at 900 degrees C in a reducing gas atmosphere to obtain Pt-Pd-Co
      nanoalloys. X-ray diffraction (XRD) analysis of the as-synthesized and 900
      degrees C heat-treated samples reveals interesting changes in phase compositions
      and degree of alloying with Co and Pt contents and heat treatment. Transmission
      electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) data of the
      as-synthesized samples confirm Pt enrichment on the surface of the Pd-Co
      nanoparticles. Rotating disk electrode (RDE) and single cell proton exchange
      membrane fuel cell measurements reveal that the as-synthesized Pt-encapsulated
      Pd(80)Co(20) (i.e., 75 wt % Pd(80)Co(20) + 25 wt % Pt) with 20 wt % total metal
      loading on carbon or 5 wt % Pt exhibit higher catalytic activity for the oxygen
      reduction reaction (ORR) compared to Pt with 20 wt % Pt loading on carbon.
      Significant changes in the catalytic activity for ORR occur on heat treatment at
      900 degrees C as a result of changes in the phase composition and increase in
      particle size. This study demonstrates that the encapsulation of Pd-Co alloys
      with Pt offers a significant enhancement in activity for ORR per unit mass of Pt,
      offering a significant cost savings.

PMID- 20141218
TI  - Molding a silver nanoparticle template on polydimethylsiloxane to efficiently
      capture mammalian cells.
AB  - Herein, a functional template made up of in situ synthesized silver nanoparticles
      (AgNPs) is prepared on polydimethylsiloxane (PDMS) for the spatial control of
      cell capture, where the residual Si-H groups in the PDMS matrix are used as
      reductants to reduce AgNO(3) for forming AgNPs. In virtue of microfluidic system,
      a one-dimensional array pattern of AgNPs is obtained easily. Further combining
      with plasma treatment, a two-dimensional array pattern of AgNPs could be
      achieved. The obtained PDMS-AgNPs composite is characterized in detail. The PDMS
      AgNPs composite shows good antibacterial property in E. coli adhesion tests. The
      patterns possess hifi and high resolution (ca. 8 microm). Cell patterns with high
      efficiency and spatial selectivity are further formed with the aid of H-Arg-Gly
      Asp-Cys-OH (RGDC) tetrapeptide which is grafted on the AgNPs template. Cells
      immobilized on the template show a good ability for adhesion, spreading,
      migration, and growth.

PMID- 20141219
TI  - Molecular analysis of tumor margins by MALDI mass spectrometry in renal
      carcinoma.
AB  - The rate of tumor recurrence post resection suggests that there are underlying
      molecular changes in nearby histologically normal tissue that go undetected by
      conventional diagnostic methods that utilize contrast agents and
      immunohistochemistry. MALDI MS is a molecular technology that has the specificity
      and sensitivity to monitor and identify molecular species indicative of these
      changes. The current study utilizes this technology to assess molecular
      distributions within a tumor and adjacent normal tissue in clear cell renal cell
      carcinoma biopsies. Results indicate that the histologically normal tissue
      adjacent to the tumor expresses many of the molecular characteristics of the
      tumor. Proteins of the mitochondrial electron transport system are examples of
      such distributions. This work demonstrates the utility of MALDI MS for the
      analysis of tumor tissue in the elucidation of aberrant molecular changes in the
      tumor microenvironment.

PMID- 20141220
TI  - Metabolomic analysis identifies inflammatory and noninflammatory metabolic
      effects of genetic modification in a mouse model of Crohn's disease.
AB  - Interleukin-10 is an immunosuppressive cytokine involved in the regulation of
      gastrointestinal mucosal immunity toward intestinal microbiota. Interleukin-10
      deficient (IL10(-/-)) mice develop Crohn's disease-like colitis unless raised in
      germ-free conditions. Previous gas chromatography-mass spectrometry (GC-MS)
      metabolomic analysis revealed urinary metabolite differences between IL10(-/-)
      and wildtype C57BL/6 mice. To determine which of these differences were
      specifically associated with intestinal inflammation arising from IL10
      deficiency, urine samples from IL10(-/-) and wildtype mice, housed in either
      conventional or specific pathogen-free conditions, were subjected to GC-MS
      metabolomic analysis. Fifteen metabolite differences, including fucose,
      xanthurenic acid, and 5-aminovaleric acid, were associated with intestinal
      inflammation. Elevated urinary levels of xanthurenic acid in IL10(-/-) mice were
      attributed to increased production of kynurenine metabolites that may induce T
      cell tolerance toward intestinal microbiota. Liquid chromatography-mass
      spectrometry analysis confirmed that plasma levels of kynurenine and 3
      hydroxykynurenine were elevated in IL10(-/-) mice. Eleven metabolite differences,
      including glutaric acid, 2-hydroxyglutaric acid, and 2-hydroxyadipic acid, were
      unaffected by the severity of inflammation. These metabolite differences may be
      associated with residual genes from the embryonic stem cells of the 129P2 mouse
      strain that were used to create the IL10(-/-) mouse, or may indicate novel
      functions of IL10 unrelated to inflammation.

PMID- 20141221
TI  - Toward the comprehensive systematic enumeration and synthesis of novel kinase
      inhibitors based on a 4-anilinoquinazoline binding mode.
AB  - There are currently eight small-molecule kinase inhibitors approved as cancer
      treatments, and a significantly larger number of compounds are in the earlier
      stages of clinical development. Although kinase inhibitors are most commonly
      developed in a cancer setting, other disease areas have been targeted. The vast
      majority of reported kinase small-molecule inhibitors contain functionalities
      that interact with the adenosine triphosphate (ATP) binding site of the kinase.
      The 4-anilinoquinazolines have previously been reported as potent epidermal
      growth factor receptor (EGFR) inhibitors, binding at the 'hinge' region of the
      ATP site. Subsequently, this chemical series has been optimized against a number
      of different kinases including Src and Aurora B. Here, we detail the
      computational enumeration of ring systems that have the ability to make
      comparable interactions to the 4-anilinoquinazoline core. These were prioritized
      by computational, medicinal, and synthetic chemistry input, and a number of
      libraries were subsequently synthesized.

PMID- 20141222
TI  - Palladium-catalyzed allylic acyloxylation of terminal alkenes in the presence of
      a base.
AB  - The efficiency and the selectivity of the Pd-catalyzed oxidation, in carboxylic
      acids, of terminal alkenes are strongly improved in the presence of a base. The
      methodology is particularly well adapted for the oxidation of homoallylic
      alcohols, for which the resulting acyloxylated products are obtained selectively
      as E-isomers in fair to good yields.

PMID- 20141223
TI  - Catalyst-controlled regioselective Suzuki couplings at both positions of
      dihaloimidazoles, dihalooxazoles, and dihalothiazoles.
AB  - Various dihaloazoles can be monoarylated at a single C-X bond with high
      selectivity via Suzuki coupling. By changing the palladium catalyst employed, the
      selectivity can be switched for some dihaloazoles, allowing for Suzuki coupling
      at the other, traditionally less reactive C-X bond. These conditions are
      applicable to coupling of a wide variety of aryl-, heteroaryl-, cyclopropyl-, and
      vinylboronic acids with high selectivities and enable the rapid construction of
      diverse arrays of diarylazoles in a modular fashion.

PMID- 20141224
TI  - Synthesis of an azide-tagged library of 2,3-dihydro-4-quinolones.
AB  - We describe the assembly of a 960-member library of tricyclic 2,3-dihydro-4
      quinolones using a combination of solution-phase high-throughput organic
      synthesis and parallel chromatographic purification. The library was produced
      with high efficiency and complete chemo- and diastereoselectivity by
      diversification of an azide-bearing quinolone via a sequence of [4 + 2]
      cycloadditions, N-acylations, and reductive aminations. The azide
      functionalization of this library is designed to facilitate subsequent
      preparation of fluorescent or affinity probes, as well as small-molecule/surface
      conjugation.

PMID- 20141225
TI  - Synthesis of fused-ring nicotine derivatives from (S)-nicotine.
AB  - The synthesis of novel fused-ring bicyclic (4-6) and tricyclic (7-10) nicotine
      derivatives from natural (S)-nicotine are described. Enantiopure bicyclic
      dioxino, dihydrofuro, and dihydropyranol nicotine derivatives as well as tricylic
      benzofuro and benzopyran derivatives were synthesized from simple alkoxy or
      halonicotine intermediates. Attempts to synthesize furonicotines (11, 12)
      resulted in formation of the furonicotine dimers 42 and 49.

PMID- 20141226
TI  - Stereoselective synthesis of the cytotoxic 14-membered macrolide aspergillide A.
AB  - A stereoselective synthesis of the cytotoxic 14-membered macrolide aspergillide A
      has been performed. The preparation of a cis-2,6-disubstituted tetrahydropyran
      ring via stereoselective reduction of an intermediate cyclic hemiacetal was one
      key feature of the synthesis. The macrocyclic lactone ring was created by means
      of a ring-closing metathesis (RCM), whereby the new C=C bond displayed
      exclusively the undesired Z configuration. Conversion to the required E
      configuration was achieved via photochemical isomerization.

PMID- 20141227
TI  - Orbitals that are unrestricted in active pairs for generalized valence bond
      coupled cluster methods.
AB  - Spin unrestriction is typically defined as a free variation of the molecular
      orbitals of different spins in order to lower the molecular energy. When applied
      to approximate active space electron correlation methods, such as generalized
      valence bond coupled cluster (GVB-CC) models, this approach often leads to
      undesirable artifacts. We therefore present an alternative unrestricted in active
      pairs (UAP) procedure for spin polarization in GVB-CC methods, which resembles
      the corresponding orbitals of unrestricted Hartree-Fock theory. The UAP procedure
      permits spin polarization only within the two orbital subspaces describing each
      electron pair (consisting of one nominally occupied and one virtual orbital).
      This great reduction to just a linear number of degrees of freedom associated
      with spin polarization eliminates many of the undesirable artifacts associated
      with unconstrained spin unrestriction. The UAP procedure is tested on a variety
      of potential curves for bond breaking and the properties of small radicals as
      well as larger polyenyl radicals, allyl, pentadienyl, and heptatrienyl.

PMID- 20141228
TI  - The role of tetracyclines in rosacea.
AB  - There is a great deal of evidence to support the use of tetracycline and
      doxycycline in the treatment of papulopustular rosacea. Nevertheless, these
      agents have shared and unique adverse effects and relative contraindications.
      Recently, subantimicrobial-dose doxycycline was demonstrated to be an effective
      treatment for rosacea, due to its inherent anti-inflammatory properties.
      Furthermore, subantimicrobial-dose doxycycline has a more preferable tolerability
      profile and a lower occurrence of bacterial resistance than traditional-dose
      doxycycline. To further elucidate the role of tetracycline agents in rosacea,
      clinical trials that compare these agents with each other as well as with other
      effective rosacea treatments are called for. Adherence studies comparing oral
      tetracycline treatment with topical metronidazole treatment may also enhance
      clinical decision making.

PMID- 20141229
TI  - The skin landscape following nonoptical capacitance imaging.
AB  - Skin capacitance is an electrical property measurable at the level of the stratum
      corneum. Values are related to the moisture content of the tissue. Using the
      silicon image sensor technology, it has recently become possible to measure
      capacitance at 50 microm intervals on the skin surface. The resulting nonoptical
      picture corresponds to skin capacitance imaging. This novel tool for
      dermatologists highlights with precision the hollow skin surface patterns,
      including dermatoglyphics, the patterns of the shallow skin lines, and wrinkles.
      The topographic heterogeneity in skin surface hydration is made visible. In
      addition, the sweat gland and follicular openings are disclosed. Skin disorders
      induced by surfactants or presenting as hyperkeratotic areas, including some
      neoplasms, may show typical aspects. It is concluded that skin capacitance
      imaging brings added value to the clinical assessment performed by
      dermatologists.

PMID- 20141230
TI  - Photoaging: prevention and topical treatments.
AB  - A rapidly increasing number of people visit dermatologists for the prevention and
      treatment of aging skin. Sun avoidance and sunscreen use are widely accepted
      strategies of primary prevention against photoaging. Convincing evidence shows
      that topical application of retinoids has an effect on reversing, at least
      partially, mild to moderate photodamage. Antioxidants and alpha-hydroxy acids can
      alter the skin structure and function. Enzymes that repair DNA damage or
      oligonucleotides that enhance the endogenous capacity for DNA damage repair may
      prove to be future preventive/therapeutic interventions for aging skin.

PMID- 20141231
TI  - The purple digit: an algorithmic approach to diagnosis.
AB  - The acute onset of purple digits is a concerning manifestation and may represent
      underlying, potentially life-threatening disease. Correctly identifying the
      etiology of purple digits is essential to proper management, and can aid in the
      diagnosis of systemic disease. Multiple causes of purple digits and significant
      overlap in clinical presentation can make diagnosis difficult. Despite the
      various causes of acute purple digits in the published literature, an algorithmic
      approach to the evaluation and management of the most common and alarming
      etiologies has yet to be established. The initial step in evaluating a patient
      with purple digits is to determine if the cause is associated with hypoxemia or
      trauma. If the patient is in a stable condition, the dermatologist needs to
      determine if the process could be related to cold exposure such as Raynaud
      phenomenon, acrocyanosis, pernio, cryoglobulinemia or frostbite. If the disease
      occurs independent of temperature, physical examination and histological
      evaluation of the skin is recommended. The lack of peripheral pulses are
      concerning for acute arterial thrombosis from peripheral vascular disease or
      arterial embolism. Non-blanching skin changes on the digit that lack inflammation
      and microthrombosis most likely represent a bleeding or platelet abnormality;
      however, if microthrombi are identified a more life-threatening processes such as
      purpura fulminans or embolic phenomenon may be occurring. Evidence of blood
      vessel inflammation suggests a leukocytoclastic vasculitis. The patient with a
      purple blanching digit and normal pulses requires an extensive historical review
      to help determine the cause. This review presents an algorithmic approach to
      assist in the evaluation and management of the purple digit.

PMID- 20141232
TI  - Gardner syndrome: skin manifestations, differential diagnosis and management.
AB  - Gardner syndrome is a variant of familial adenomatous polyposis (FAP) and results
      in the manifestation of numerous external and internal symptoms including
      gastrointestinal polyps, osteomas, tumors, and epidermoid cysts. As such, it is
      highly recommended that physicians conduct full body examinations to catch the
      key clinical features of the disease when it is suspected. Stemming from a
      mutation in the adenomatous polyposis coli (APC) gene, Gardner syndrome shares
      genetic correlations with the FAP phenotype; as a result, it becomes all the more
      crucial for physicians to be able to discern Gardner syndrome from other
      differential diagnoses such as Turcot syndrome, FAP, and other attenuated forms
      of familial polyposis. Fortunately, Gardner syndrome has characteristic polyps in
      the colon, osteomas, and also exhibits abnormalities in the retinal epithelium
      that discern it from others. Surgery is the most effective method of management
      for Gardner syndrome; restorative proctocolectomy with ileal pouch anal
      anastomosis with mucosectomy is the top choice for colonic malignancies, and skin
      manifestations can be treated through a variety of excisions and therapy
      depending on location, size, and number of malignancies. Currently, there are no
      specific screening recommendations for Gardner syndrome, but testing following
      general screening recommendations for extra-colonic malignancies, genetic
      counseling, and endoscopy are encouraged.

PMID- 20141233
TI  - Dexamethasone-cyclophosphamide pulse therapy in pemphigus: a review of 72 cases.
AB  - BACKGROUND: Autoimmune pemphigus is a group of severe blistering diseases.
      Although corticosteroids have dramatically altered the prognosis of pemphigus,
      morbidity and mortality resulting from the adverse effects of systemic
      corticosteroids remain high. Dexamethasone-cyclophosphamide pulse (DCP) therapy
      was introduced to diminish the adverse effects of prolonged conventional daily
      dose regimens. OBJECTIVE: To report our experience with the use of the DCP
      regimen in patients with autoimmune pemphigus. METHODS: In the period 1998-2002,
      72 patients with various forms of autoimmune pemphigus treated with DCP therapy
      were included, of whom 36 patients were previously treated with conventional
      corticosteroid therapy, and 36 were newly diagnosed patients. RESULTS: Of the 72
      patients, 43 completed treatment, while 13 patients did not respond adequately to
      the treatment and continued with the conventional daily regimen, nine patients
      were lost to follow-up, and seven patients died. Two of these deaths were
      probably a consequence of DCP therapy. CONCLUSION: DCP regimen is a beneficial
      treatment for patients with pemphigus, sparing the adverse effects of
      conventional regimens.

PMID- 20141234
TI  - Cutaneous adverse effects of ketoprofen for topical use: clinical patterns and
      costs.
AB  - BACKGROUND: Since its introduction in France, ketoprofen for topical use has been
      associated with a large number of cutaneous adverse effect reports. Therefore,
      the French Medicine Agency progressively introduced warnings and
      contraindications to its use. Despite this, serious adverse drug reactions (ADRs)
      still occur. OBJECTIVE: To describe clinical patterns and estimate costs of
      spontaneously reported cutaneous ADRs of topical ketoprofen. METHODS: All cases
      of cutaneous ADRs of topical ketoprofen reported to the Bordeaux regional
      pharmacovigilance center between January 1989 and December 2006 were included.
      Clinical patterns, in respect of adherence to recommendations, causality,
      seriousness, and direct costs incurred by the ADRs, were assessed. RESULTS: A
      total of 136 cases were reported (median age: 42 years, 55.9% women). Proper use
      of topical ketoprofen regarding indications, warnings, and contraindications was
      not respected by one-third of the patients. Almost all cases occurred during
      sunny months. Symptoms consisted predominantly of bullous eruptions (29.4%) or
      contact dermatitis (27.2%). Generalized lesions were observed in 37.5% of
      patients. Causality was considered at least possible for most of the cases
      (92.6%). These ADRs induced hospital admission in 15 cases (11.0%). The total
      estimated cost was euro 42,962 ($US 66,559), corresponding to euro 316 per case.
      This mean cost was nine times higher for serious ADRs. CONCLUSION: Topical
      ketoprofen is used to treat benign symptoms but can be associated with serious
      and costly cutaneous ADRs. Furthermore, the number of cases and the calculated
      costs may have been greatly under-estimated in the present study.

PMID- 20141235
TI  - Oropharyngeal pemphigus vulgaris and clinical remission: a long-term,
      longitudinal study.
AB  - BACKGROUND: The pattern of clinical remission in pemphigus vulgaris patients
      still remains a controversial issue because of the limited data reported in the
      literature. OBJECTIVE: To evaluate the time to clinical remission in patients
      with exclusive oropharyngeal pemphigus vulgaris. METHODS: We conducted a long
      term, longitudinal study in a university hospital. We treated 37 patients with
      oropharyngeal pemphigus vulgaris, who underwent a periodic follow-up for an
      average of 5.3 years, and evaluated their outcome in terms of clinical remission.
      The main outcome measure was the clinical outcome (assessed by objective measures
      of severity, extent of disease, intensity of therapy, and remission) before and
      after conventional immunosuppressive therapy. RESULTS: Complete and long-lasting
      clinical remission was achieved in 35 patients (94.6%) with oropharyngeal
      lesions, of whom 13 (35.1%) were off therapy and 21 (56.8%) were on therapy at
      the last evaluation. One patient (2.7%) died following a stroke 3 years after
      complete remission on therapy. Partial remission was achieved in two patients
      (5.4%). The mean time to achieve complete clinical remission was 4.7 +/- 2.57
      months after commencement of therapy. In all patients the mean disease severity
      score decreased from 7.81 +/- 1.35 at time of diagnosis to 1.0 +/- 0.9 at time of
      clinical remission (p < 0.0001 vs baseline), while the extent of the disease
      decreased from 2.9 +/- 1.0 to 0.27 +/- 0.45 (p < 0.0019 vs baseline) and the
      intensity of therapy from 4.91 +/- 0.64 to 0.70 +/- 0.57 (p < 0.0001 vs
      baseline). The mean duration of complete remission was 63.53 +/- 44.9 months.
      CONCLUSIONS: In almost all patients with oropharyngeal pemphigus vulgaris it was
      possible to schedule a safe tapering of the conventional immunosuppressive
      therapy very shortly after the disease was controlled. Thus, we may conclude
      that: (i) the percentage of patients with oropharyngeal pemphigus vulgaris who
      achieved complete long-lasting clinical remission was very high; (ii) transient
      lesions that healed within a week were very frequent and had to be actively
      controlled; (iii) if treated early, most patients had a good clinical response
      and could achieve a disease- and drug-free clinical remission; (iv) early
      treatment may prevent extension or progression of disease; (v) there is a
      possible role for immunosuppressive agents; and (vi) a more favorable course of
      the disease, in terms of attainment and duration of clinical remission and a
      better prognosis, seemed to be related to a rapid response to therapy rather than
      to the initial severity and extent of the disease.

PMID- 20141236
TI  - A case with an indolent course of subcutaneous panniculitis-like T-cell lymphoma
      demonstrating Epstein-Barr virus positivity and simulating dermatitis artefacta.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of
      cytotoxic T-cell lymphoma. The disease has a poor prognosis in patients with the
      complication of hemophagocytic syndrome, especially in those with Epstein-Barr
      virus (EBV) positivity. A 20-year-old woman presented with multiple, itchy,
      purplish nodules and excoriations on both of her upper limbs. The
      histopathologic, immunohistochemical staining, and clonal T-cell receptor gene
      rearrangement examinations of skin lesions revealed the diagnosis of SPTCL. In
      situ hybridization performed for EBV was positive. There were no findings
      suggesting systemic involvement of SPTCL, or hemophagocytic syndrome. The lesions
      improved with systemic corticosteroid therapy and radiotherapy, with no
      recurrence. We present a patient with a protracted course of SPTCL in whom EBV
      positivity was demonstrated. This apparent conflict may be explained by
      geographic and ethnic variations in EBV infection. Further studies may shed light
      on the real relationship between EBV-RNA and the course of SPTCL.

PMID- 20141237
TI  - A rare lymphoma in a patient with amyopathic dermatomyositis.
AB  - A 37-year-old Caucasian woman was evaluated for a photosensitive dermatitis. A
      positive anti-nuclear antibody with a titer of 1 : 1280 and a speckled pattern
      was noted and she was diagnosed with subacute cutaneous lupus erythematosus
      (SCLE). Although the initial dermatologic diagnosis was SCLE, a skin biopsy
      suggested the additional possibility of dermatomyositis because of increased
      dermal mucin. We began following her at the request of the dermatology
      department, and a diagnosis of amyopathic dermatomyositis was made based on the
      lack of objective muscle weakness, normal muscle enzymes, negative double
      stranded DNA, SSA/SSB, and RNP/Smith antibody panel, and especially on the
      cutaneous examination findings. A malignancy evaluation included a normal CT scan
      of her chest, abdomen, and pelvis, esophagogastroduodenoscopy, colonoscopy,
      mammography, pelvic ultrasound, Papanicolaou smear, and endometrial biopsy. She
      developed vaginal bleeding 1 year after the onset of her skin manifestations.
      Repeat gynecologic evaluation, including cervical biopsy, revealed a large B-cell
      cervical lymphoma. Amyopathic dermatomyositis and lymphoma of the cervix are both
      rare conditions. Our case emphasizes the importance of considering underlying
      malignancy at the time of diagnosis and while the patient is followed clinically.
      Additionally, the clinician must remain vigilant in evaluating any new clinical
      changes in follow-up care. To our knowledge, this is the first documented case of
      lymphoma of the cervix in the setting of amyopathic dermatomyositis.

PMID- 20141238
TI  - Genetic and environmental influences on ADHD symptom dimensions of inattention
      and hyperactivity: a meta-analysis.
AB  - Behavioral genetic investigations have consistently demonstrated large genetic
      influences for the core symptom dimensions of attention-deficit/hyperactivity
      disorder (ADHD), namely inattention (INATT) and hyperactivity (HYP). Yet little
      is known regarding potential similarities and differences in the type of genetic
      influence (i.e., additive vs. nonadditive) on INATT and HYP. As these symptom
      dimensions form the basis of the current Diagnostic and Statistical Manual of
      Mental Disorders subtype classification system, evidence of differential genetic
      influences would have important implications for research investigating causal
      mechanisms for ADHD. The current meta-analysis aimed to investigate the nature of
      etiological influences for INATT and HYP by comparing the type and magnitude of
      genetic and environmental influences each. A comprehensive literature search
      yielded 79 twin and adoption studies of INATT and/or HYP. Of these, 13 samples of
      INATT and 9 samples of HYP were retained for analysis. Results indicated that
      both dimensions were highly heritable (genetic factors accounted for 71% and 73%
      of the variance in INATT and HYP, respectively). However, the 2 dimensions were
      distinct as to the type of genetic influence. Dominant genetic effects were
      significantly larger for INATT than for HYP, whereas additive genetic effects
      were larger for HYP than for INATT. Estimates of unique environmental effects
      were small to moderate and shared environmental effects were negligible for both
      symptom dimensions. The pattern of results generally persisted across several
      moderating factors, including gender, age, informant, and measurement method.
      These findings highlight the need for future studies to disambiguate INATT and
      HYP when investigating the causal mechanisms, and particularly genetic
      influences, behind ADHD.

PMID- 20141239
TI  - Electrophysiological correlates of emotional responding in schizophrenia.
AB  - People with schizophrenia consistently report normal levels of pleasant emotion
      when exposed to evocative stimuli, suggesting intact consummatory pleasure.
      However, little is known about the neural correlates and time course of emotion
      in schizophrenia. This study used a well-validated affective picture viewing task
      that elicits a characteristic pattern of event-related potentials (ERPs) from
      early to later processing stages (i.e., P1, P2, P3, and late positive potentials
      [LPPs]). Thirty-eight stabilized outpatients with schizophrenia and 36 healthy
      controls viewed standardized pleasant, unpleasant, and neutral pictures while
      ERPs were recorded and subsequently rated their emotional responses to the
      stimuli. Patients and controls responded to the pictures similarly in terms of
      their valence ratings, as well as the initial ERP components (P1, P2, and P3).
      However, at the later LPP component (500-1,000 ms), patients displayed diminished
      electrophysiological discrimination between pleasant versus neutral stimuli. This
      pattern suggests that patients demonstrated normal self-reported emotional
      experience and intact initial sensory processing of and resource allocation to
      emotional stimuli. However, they showed a disruption in a later component
      associated with sustained attentional processing of emotional stimuli.

PMID- 20141240
TI  - Attentional modulation of the P50 suppression deficit in recent-onset and chronic
      schizophrenia.
AB  - Schizophrenia is associated with deficits in P50 suppression to the second
      stimulus in a pair, a process often conceptualized as a preattentive index of
      sensory gating. This study assessed the malleability of the deficit by
      determining whether early attentional control can influence P50 gating across
      different phases of schizophrenia. Participants included 28 patients in the
      recent-onset (n = 16) or chronic (n = 12) phase of illness and 28 healthy
      comparison subjects. During the standard paradigm, chronic schizophrenia patients
      exhibited impaired P50 suppression relative to healthy subjects, whereas recent
      onset schizophrenia patients were intermediate. Directing voluntary attention
      toward the initial stimulus yielded substantial improvements in the P50 ratio;
      recent-onset schizophrenia patients achieved ratio scores comparable to those of
      healthy participants, whereas chronic patients also improved and could no longer
      be distinguished clearly from the healthy comparison sample. Directing attention
      toward the second stimulus enhanced P50 amplitude to the second stimulus across
      groups, possibly because activation of the inhibitory mechanism was overridden or
      circumvented by task demands. Thus, P50 suppression may be primarily preattentive
      under standard conditions, but manipulation of early attention can exert a
      modulatory influence on P50, indicating that the suppression deficit is malleable
      in schizophrenia without pharmacological agents.

PMID- 20141241
TI  - The jumping to conclusions bias in delusions: specificity and changeability.
AB  - There are indications that a jumping to conclusions bias (JTC) plays a role in
      the formation and maintenance of delusions and should be targeted in therapy.
      However, it is unclear whether (a) JTC is uniquely associated with delusions or
      simply an epiphenomenon of schizophrenia or impaired intellectual functioning and
      (b) it can be changed by varying task demands, motivational factors, or feedback.
      Seventy-one patients with schizophrenia spectrum disorders and either acute or
      remitted delusions and 68 healthy controls were included. Patients were assessed
      with self- and observer-rated symptom measures. All participants were assessed
      for intellectual ability and performed the classic beads task with a ratio of
      80:20. They were then presented with task variations that involved increasing the
      difficulty of the ratio to 60:40, introducing a rule for which correct decisions
      were rewarded by monetary gains and false decisions led to financial losses, and
      providing feedback on the accuracy of the previous decisions. Participants with
      current delusional symptoms took fewer draws to decision (DTD) than did those in
      remission and healthy controls. DTD were associated with observer-rated
      delusions, but controlling for negative symptoms or intelligence rendered this
      association insignificant. DTD increased after the difficulty of the task
      increased and after feedback. The study demonstrated that JTC is linked to
      delusions but that this association is not unique. Patients with delusions are
      principally able to adapt their decisions to altered conditions but still decide
      relatively quickly even when decisions have negative consequences. These
      difficulties might stem in part from impaired intellectual functioning.

PMID- 20141242
TI  - Emotion responsivity, social cognition, and functional outcome in schizophrenia.
AB  - Social functioning deficits have long been a defining feature in schizophrenia,
      but relatively little research has examined how emotion responsivity influences
      functional outcome in this disorder. The goal of the current study was to begin
      to elucidate the relationships between emotion responsivity, social cognition,
      and functional outcome in schizophrenia. Participants were 40 outpatients
      diagnosed with schizophrenia or schizoaffective disorder according to the
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American
      Psychiatric Association, 1994) and 40 controls. Each participant completed
      measures of emotion responsivity, social cognition (both emotion and social
      perception), and functional outcome. Individuals with schizophrenia demonstrated
      somewhat reduced emotion responsivity for positive and negative stimuli, as well
      as deficits in both social cognition and functional outcome, in comparison with
      controls. Additionally, results indicated that both social perception and emotion
      responsivity were positively correlated with functional outcome. Importantly, the
      relationship of emotion responsivity to functional outcome was not mediated by
      social perception and showed a significant relationship to functional outcome
      independent of social cognition. This finding suggests that emotion responsivity
      is an important factor in understanding functional outcome in schizophrenia.

PMID- 20141243
TI  - An examination of the relative contribution of saturation and selective attention
      to memory deficits in patients with recent-onset schizophrenia and their
      unaffected parents.
AB  - Cognitive dysfunctions in patients suffering from schizophrenia (SZ) are also
      found in their unaffected parents though to a lesser degree. According to several
      researchers, short-term memory (STM) deficits are a potential marker of
      vulnerability to SZ. However, the cognitive processes underlying the observed STM
      deficits remain underspecified in SZ (Lee & Park, 2005). In the present study,
      our goal was to pinpoint those processes at play in the manifestation of STM
      deficits by using the paradigm of the sandwich effect (e.g., Hitch, 1975) to
      manipulate information load (5 vs. 7 to-be-remembered items) and distraction
      (control vs. sandwich) in the verbal domain. Our study comprises four groups:
      patients with SZ (n = 25), their unaffected parents (n = 25), and their
      respective healthy controls. The pattern of results indicates a generalized
      dysfunction of STM in patients with SZ characterized by saturation and an
      increased susceptibility to distraction. The impact of saturation and distraction
      was also observed in unaffected parents of patients with SZ to a lesser degree.
      The methodological strategy adopted here allowed us to show that the dysfunction
      of STM is genuine, can be aggravated by deficits in selective attention, and is a
      good candidate for further research on genetic epidemiology.

PMID- 20141244
TI  - Integrity of emotional and motivational states during the prodromal, first
      episode, and chronic phases of schizophrenia.
AB  - Emotional and motivational dysfunction is fundamental to schizophrenia, and yet,
      the nature and scope of associated deficits are not well understood. This study
      assessed the integrity of emotional responding from the perspective of its
      underlying motivational systems during different phases of schizophrenia.
      Evaluative, somatic, and autonomic responses were measured during viewing of
      pictures categorized by emotional content, including threat, mutilation,
      contamination, illness, pollution, mild erotica, families, food, and nature.
      Participants were 13 patients at ultra high risk or prodromal for psychosis, 40
      first-episode schizophrenia patients, 37 chronic schizophrenia patients, and 74
      healthy comparison subjects. Irrespective of phase of illness, schizophrenia
      patients showed a robust and normal pattern of response across multiple systems,
      with differential engagement of the defensive and appetitive systems as a
      function of the motivational significance assigned to specific emotional
      contexts. Although the integrity of core motivational states also appeared to be
      intact in prodromal patients, a less consistent pattern of response was observed.
      As continuing efforts are made to identify emotional and motivational
      abnormalities in schizophrenia, identified deficits will likely be independent of
      a fundamental dysfunction in basic emotion and motivation response systems and
      involve integration with higher order processes.

PMID- 20141245
TI  - Testing the continuum of delusional beliefs: an experimental study using virtual
      reality.
AB  - A key problem in studying a hypothesized spectrum of severity of delusional
      ideation is determining that ideas are unfounded. The first objective was to use
      virtual reality to validate groups of individuals with low, moderate, and high
      levels of unfounded persecutory ideation. The second objective was to
      investigate, drawing upon a cognitive model of persecutory delusions, whether
      clinical and nonclinical paranoia are associated with similar causal factors.
      Three groups (low paranoia, high nonclinical paranoia, persecutory delusions) of
      30 participants were recruited. Levels of paranoia were tested using virtual
      reality. The groups were compared on assessments of anxiety, worry, interpersonal
      sensitivity, depression, anomalous perceptual experiences, reasoning, and history
      of traumatic events. Virtual reality was found to cause no side effects.
      Persecutory ideation in virtual reality significantly differed across the groups.
      For the clear majority of the theoretical factors there were dose-response
      relationships with levels of paranoia. This is consistent with the idea of a
      spectrum of paranoia in the general population. Persecutory ideation is clearly
      present outside of clinical groups and there is consistency across the paranoia
      spectrum in associations with important theoretical variables.

PMID- 20141246
TI  - Do changes in drinking motives mediate the relation between personality change
      and "maturing out" of problem drinking?
AB  - Recent research has indicated that developmental changes in the personality
      traits of neuroticism and impulsivity correlate with changes in problem drinking
      during emerging and young adulthood. However, it remains unclear what potential
      mechanisms, or mediators, could account for these associations. Drinking motives,
      particularly drinking to regulate negative affect (drinking to cope) and to get
      "high" or "drunk" (drinking for enhancement), have been posited to mediate the
      relationship between personality and drinking problems. Recent work indicates
      that changes in drinking motives parallel changes in alcohol involvement from
      adolescence to young adulthood. The present study examined changes in drinking
      motives (i.e., coping and enhancement) as potential mediators of the relation
      between changes in personality (impulsivity and neuroticism) with changes in
      alcohol problems in emerging and young adulthood. Analyses were based on data
      collected from a cohort of college students (N = 489) at varying risk for alcohol
      use disorders from ages 18 to 35. Parallel process latent growth modeling
      indicated that change in coping (but not enhancement) motives specifically
      mediated the relation between changes in neuroticism and alcohol problems as well
      as the relation between changes in impulsivity and alcohol problems. Findings
      suggest that change in coping motives is an important mechanism in the relation
      between personality change and the "maturing out" of problematic alcohol
      involvement.

PMID- 20141247
TI  - Alcohol demand, delayed reward discounting, and craving in relation to drinking
      and alcohol use disorders.
AB  - A behavioral economic approach to alcohol use disorders (AUDs) emphasizes both
      individual and environmental determinants of alcohol use. The current study
      examined individual differences in alcohol demand (i.e., motivation for alcohol
      under escalating conditions of price) and delayed reward discounting (i.e.,
      preference for immediate small rewards compared to delayed larger rewards) in 61
      heavy drinkers (62% with an AUD). In addition, based on theoretical accounts that
      emphasize the role of craving in reward valuation and preferences for immediate
      rewards, craving for alcohol was also examined in relation to these behavioral
      economic variables and the alcohol-related variables. Intensity of alcohol demand
      and delayed reward discounting were significantly associated with AUD symptoms,
      but not with quantitative measures of alcohol use, and were also moderately
      correlated with each other. Likewise, craving was significantly associated with
      AUD symptoms, but not with alcohol use, and was also significantly correlated
      with both intensity of demand and delayed reward discounting. These findings
      further emphasize the relevance of behavioral economic indices of motivation to
      AUDs and the potential importance of craving for alcohol in this relationship.

PMID- 20141249
TI  - All PTSD symptoms are highly associated with general distress: ramifications for
      the dysphoria symptom cluster.
AB  - This study used longitudinal data collected from two trauma-exposed samples,
      survivors of community violence (N = 294) and wildfire evacuees (N = 234), to
      examine a key claim underlying a proposed reformulation of the symptom structure
      of posttraumatic stress disorder (PTSD). This theory, which we term the PTSD
      dysphoria model, posits that 8 of 17 symptoms of PTSD reflect dysphoria or
      general psychological distress and might be deemphasized to improve the utility
      of the PTSD construct (Simms, Watson, & Doebbeling, 2002). For each sample, we
      analyzed PTSD symptoms and measures of general distress administered at 2 time
      points. A consistent pattern of findings was observed across assessments for each
      sample: All 17 PTSD symptoms were highly associated with measures of general
      distress. Moreover, we found no evidence that dysphoria symptoms were more highly
      correlated than PTSD-specific symptoms with general distress. Results call into
      question both the conceptual basis and the clinical utility of differentiating
      between symptoms that appear to be relatively specific to PTSD and those that
      seem more broadly characteristic of general psychological distress.

PMID- 20141248
TI  - Polymorphisms of the mu-opioid receptor and dopamine D4 receptor genes and
      subjective responses to alcohol in the natural environment.
AB  - Polymorphisms of the mu-opioid receptor (OPRM1) and dopamine D4 receptor (DRD4)
      genes are associated with subjective responses to alcohol and urge to drink under
      laboratory conditions. This study examined these associations in the natural
      environment using ecological momentary assessment. Participants were non
      treatment-seeking heavy drinkers (n = 112, 52% female, 61% alcohol dependent) who
      enrolled in a study of naltrexone effects on craving and drinking in the natural
      environment. Data were culled from 5 consecutive days of drinking reports prior
      to medication randomization. Analyses revealed that, after drinking, carriers of
      the Asp40 allele of the OPRM1 gene reported higher overall levels of vigor and
      lower levels negative mood, as compared to homozygotes for the Asn40 variant.
      Carriers of the long allele (i.e., >or=7 tandem repeats) of the DRD4 endorsed
      greater urge to drink than homozygotes for the short allele. Effects of OPRM1 and
      DRD4 variable-number-of-tandem-repeats genotypes appear to be alcohol dose
      dependent. Specifically, carriers of the DRD4-L allele reported slight decreases
      in urge to drink at higher levels of estimated blood alcohol concentration
      (eBAC), and Asp40 carriers reported decreases in vigor and increases in negative
      mood as eBAC rose, as compared to carriers of the major allele for each gene.
      Self-reported vigor and urge to drink were positively associated with alcohol
      consumption within the same drinking episode. This study extends findings on
      subjective intoxication, urge to drink, and their genetic bases from controlled
      laboratory to naturalistic settings.

PMID- 20141250
TI  - The effect of attention training on a behavioral test of contamination fears in
      individuals with subclinical obsessive-compulsive symptoms.
AB  - In the current study, we evaluated the effectiveness of attention training in
      individuals with subclinical obsessive-compulsive symptoms. We hypothesized that
      after completing attention training, participants would be more likely to
      complete steps in a hierarchy approaching their feared contaminant compared with
      participants in the control condition. Participants completed a probe detection
      task by identifying letters replacing one member of a pair of words (neutral or
      contamination related). We trained attention by building a contingency between
      the location of the contamination-related word in the active condition and not in
      the control condition. Participants in the active group showed a significant
      reduction in attention bias for threat and completed significantly more steps
      when approaching their feared objects compared with participants in the control
      group. Our results suggest that attention disengagement training may facilitate
      approaching feared objects in individuals with obsessive-compulsive symptoms.

PMID- 20141251
TI  - Anxiety sensitivity and PTSD symptom severity are reciprocally related: evidence
      from a longitudinal study of physical trauma survivors.
AB  - Cross-lagged panel analysis of interview data collected from survivors of
      traumatic physical injury (N = 677) was used to examine the temporal relationship
      between anxiety sensitivity and posttraumatic stress disorder (PTSD) symptom
      severity. The 2 constructs were assessed at 3 time points: within days of
      physical injury, at 6-month follow-up, and at 12-month follow-up. Results
      indicated that anxiety sensitivity and PTSD symptom severity were reciprocally
      related such that anxiety sensitivity predicted subsequent PTSD symptom severity,
      and symptom severity predicted later anxiety sensitivity. Findings have both
      theoretical and clinical implications.

PMID- 20141252
TI  - Externalizing psychopathology and marital adjustment in long-term marriages:
      results from a large combined sample of married couples.
AB  - The current study evaluated the associations between externalizing
      psychopathology and marital adjustment in a combined sample of 1,805 married
      couples. We further considered the role of personality in these associations, as
      personality has been found to predict both the development of externalizing
      psychopathology as well as marital distress and instability. Diagnostic
      interviews assessed conduct disorder, adult symptoms of antisocial personality
      disorder, and alcohol dependence. Personality was assessed using the
      Multidimensional Personality Questionnaire. The Dyadic Adjustment Scale was used
      to measure marital adjustment. Results indicate that more externalizing
      psychopathology, greater negative emotionality, and lower communal positive
      emotionality were associated with reduced marital adjustment in both individuals
      and their spouses. Low constraint was associated with reduced marital adjustment
      for individuals but not for their spouses. Multivariate analyses indicated
      externalizing psychopathology continued to predict marital adjustment even when
      accounting for overlap with personality. These results highlight the importance
      of examining the presence of externalizing psychopathology and the personality
      attributes of both members of a dyad when considering psychological predictors of
      marital adjustment.

PMID- 20141254
TI  - Working memory demands impair skill acquisition in children with ADHD.
AB  - This study examined the process of cognitive skill acquisition under differential
      working memory (WM) load conditions in children with the primarily inattentive (n
      = 21) and the combined (n = 32) subtypes of childhood attention
      deficit/hyperactivity disorder (ADHD) and compared the results with those of non
      ADHD controls (n = 48). Children completed 2 tasks of cognitive skill
      acquisition: alphabet arithmetic and finger math. The tasks differed in the
      amount of WM required for execution (alphabet arithmetic required more) but were
      otherwise matched with respect to logical structure, design, and discriminatory
      power. As would be predicted if the WM of the to-be-learned task affected the
      ability of children with ADHD to develop automaticity for a complex cognitive
      skill, ADHD-related impairments in the development of automaticity were seen for
      alphabet arithmetic but not for finger math. Results not only are relevant to
      ongoing debate regarding the presence of effortful versus automatic cognitive
      deficits in ADHD but also have implications for the development of new
      psychoeducational interventions for children with ADHD.

PMID- 20141253
TI  - Anxiety disorders and intimate relationships: a study of daily processes in
      couples.
AB  - Although adults with anxiety disorders often report interpersonal distress, the
      degree to which anxiety is linked to the quality of close relationships remains
      unclear. The authors examined the relational impact of anxiety by sampling the
      daily mood and relationship quality of 33 couples in which the wife was diagnosed
      with an anxiety disorder. Use of a daily process design improved on prior
      methodologies by capturing relational processes closer to their actual occurrence
      and in the setting of the diagnosed partner's anxiety. Analyses revealed
      significant associations between wives' daily anxiety and both partners'
      perceptions of relationship quality. Associations were moderated by anxiety
      specific support. Results also indicated significant concordance between wives'
      daily anxiety and husbands' distress. Concordance was stronger for husbands who
      reported frequent accommodation of wives' anxiety symptoms. Findings are
      discussed in the context of existing evidence on the social costs of anxiety
      disorders.

PMID- 20141256
TI  - Shame aversion and shame-proneness in Cluster C personality disorders.
AB  - The associations between shame and Cluster C personality disorders (PDs) were
      examined in 237 undergraduates, 35 of whom met at least subthreshold criteria for
      Cluster C PDs assessed using the Personality Disorder Interview-IV. Shame
      proneness (the propensity to experience shame across many situations) was
      measured using the Test of Self-Conscious Affect-3, and shame aversion (the
      tendency to perceive shame as especially painful and undesirable) was measured
      using the Shame-Aversive Reactions Questionnaire. A go/no-go association task was
      used to assess the strength of implicit mental representations of the association
      between shame and pain, relative to that between shame and pleasure. Shame
      proneness and shame aversion were associated with Cluster C PD symptoms over and
      above trait positive and negative affect. Further, shame-proneness was found to
      be associated with Cluster C PDs among individuals with high but not low levels
      of shame aversion. Finally, shame-pain associations were uniquely associated with
      dependent personality disorder.

PMID- 20141255
TI  - A person-centered personality approach to heterogeneity in attention
      deficit/hyperactivity disorder (ADHD).
AB  - Person-centered personality approaches are an underused means of illuminating
      clinical heterogeneity of attention-deficit/hyperactivity disorder (ADHD). In the
      present study, latent profile analysis was conducted with personality traits to
      identify homogeneous profiles within the ADHD population. Participants were 548
      children ages 6-18 years (302 with ADHD). Personality traits were measured via
      parent report on the California Q-Sort (A. Caspi et al., 1992). Latent profile
      analysis was conducted on the Big 5 factors. A 6-profile solution best fit the
      data. Resulting groups were characterized as "disagreeable," "introverted," "poor
      control," "well adjusted," "extraverted," and "perfectionistic." External
      validation of this model using ADHD diagnosis, subtypes, and comorbid
      psychopathology suggested that children with ADHD could be parsed into 4 groups:
      (a) an introverted group with high rates of the ADHD-inattentive type, (b) a
      group characterized by poor control, with high rates of ADHD-combined type (ADHD
      C) and comorbid disruptive behavior disorders, (c) an extraverted group, with
      ADHD-C and few associated comorbid disorders, and (c) possibly, a very rare
      "perfectionistic" group, exhibiting obsessive traits. A person-centered
      personality approach may be one promising way to capture homogeneous subgroups
      within the ADHD population.

PMID- 20141257
TI  - Risk factors for clinically significant importance of shape and weight in
      adolescent girls.
AB  - The objective of the current study was to conduct a longitudinal study of
      adolescent girls to determine how temperament, attitudes toward shape and weight,
      life events, and family factors might contribute to the growth of clinically
      significant importance of shape and weight, assessed using the Eating Disorder
      Examination (EDE). Time 1 data were available from 699 female twins (M age =
      13.96 years) and 595 parents, and approximately 1.15 years later (Time 2) the
      twins completed the EDE again (M age = 15.10 years). Twins were treated as
      singletons in the analyses. Time 1 importance of shape and weight was a
      significant predictor of Time 2 lifetime disordered eating behaviors. Seven Time
      1 variables were significant univariate predictors of Time 2 importance of shape
      and weight. In multivariate analyses, fathers' sensitivity to reward was the only
      significant predictor of growth of Time 2 importance of shape and weight. Some
      support was found for established risk factors of disordered eating risk, while
      the multivariate analyses highlight the importance of developing
      conceptualizations of eating disorder etiology beyond the individual level.

PMID- 20141258
TI  - Sex-specific association between psychopathic traits and electrodermal reactivity
      in children.
AB  - This study investigated the relationship of skin conductance response (SCR) to a
      child psychopathy measure. Blunted electrodermal activity is a theoretically
      important characteristic of psychopathy, but it has not been fully explored in
      preadolescents or females. The authors tested the hypothesis that reduced SCR
      magnitude is associated with psychopathic-like traits in boys and girls.
      Participants were drawn from an ethnically diverse community sample of 9- to 10
      year-old twins. Given the fact that members of each twin pair were rated by the
      same individual (i.e., their caregiver) on the Child Psychopathy Scale, the
      authors examined individual differences at the within-family level. Skin
      conductance data were collected during a passive auditory task consisting of 75
      dB tones as well as miscellaneous sounds (e.g., baby cries, bird noises, and
      speech-like stimuli). Reduced SCR magnitude (hyporeactivity) was characteristic
      only of boys with higher psychopathy scores. More specifically, electrodermal
      hyporeactivity was linked to the interpersonal facet of psychopathy, suggesting
      that it is a biological marker of a manipulative and deceitful orientation in
      males. No association was found between SCRs and psychopathic traits in girls,
      indicating the importance of sex specific etiologies of psychopathy in childhood.

PMID- 20141259
TI  - Distorted symptom perception in patients with medically unexplained symptoms.
AB  - The present study investigated differences in symptom perception between a
      clinical sample with medically unexplained symptoms (MUS) and a matched healthy
      control group. Participants (N = 58, 29 patients) were told that they would
      inhale different gas mixtures that might induce symptoms. Next, they went through
      2 subsequent rebreathing trials consisting of a baseline (60 s room air
      breathing), a rebreathing phase (150 s, which gradually increased ventilation,
      PCO2 in the blood, and perceived dyspnea), and a recovery phase (150 s, returning
      to room air breathing). Breathing behavior was continuously monitored, and
      dyspnea was rated every 10 s. The within-subject correlations between dyspnea on
      the one hand and end-tidal CO2 and minute ventilation on the other were used to
      index the degree to which perceived dyspnea was related to specific relevant
      respiratory changes. The results showed that perceived symptoms were less
      strongly related to relevant physiological parameters in MUS patients than in
      healthy persons, specifically when afferent physiological input was relatively
      weak. This suggests a stronger role for top-down psychological processes in the
      symptom perception of patients with MUS.

PMID- 20141260
TI  - Facilitating a benign attentional bias reduces negative thought intrusions.
AB  - The causal role of biased attention in worry was investigated in an experiment in
      which high worriers were assigned either to a condition requiring attention to
      nonthreatening words and text while ignoring worry-related material or to a mixed
      attention control condition. The former procedure led to fewer negative thought
      intrusions in a worry test (as rated by both participants and an assessor) than
      did the control condition. These findings suggest that attentional bias plays a
      causal role in worry and that its modification can reduce excessive worry.

PMID- 20141261
TI  - Neural responses to masked fear faces: sex differences and trauma exposure in
      posttraumatic stress disorder.
AB  - Although women have a greater propensity than men to develop posttraumatic stress
      disorder (PTSD) following trauma, sex differences in neural activations to threat
      have received little investigation. This study tested the prediction that trauma
      would heighten activity in automatic fear-processing networks to a greater extent
      in women than in men. Functional magnetic resonance imaging (fMRI) data were
      recorded in 23 participants with PTSD (13 women, 10 men), 21 trauma-exposed
      controls (9 women, 12 men), and 42 non-trauma-exposed controls (22 women, 20 men)
      while they viewed masked facial expressions of fear. Exposure to trauma was
      associated with enhanced brainstem activity to fear in women, regardless of the
      presence of PTSD, but in men, it was associated only with the development of
      PTSD. Men with PTSD displayed greater hippocampal activity to fear than did
      women. Both men and women with PTSD showed enhanced amygdala activity to fear
      relative to controls. The authors conclude that greater brainstem activation to
      threat stimuli may contribute to the greater prevalence of PTSD in women, and
      greater hippocampal activation in men may subserve an enhanced capacity for
      contextualizing fear-related stimuli.

PMID- 20141262
TI  - The craving to smoke in flight attendants: relations with smoking deprivation,
      anticipation of smoking, and actual smoking.
AB  - In the study, the authors examined the effects of smoking deprivation,
      anticipation of smoking, and actual smoking on the craving to smoke. Flight
      attendants who were light to heavy smokers rated their craving to smoke at
      predetermined time points during a 2-way short flight (each leg 3-5.5 hr) and a 1
      way long flight (8-13 hr). In both short and long flights, craving increased
      gradually and peaked as landing approached. Craving levels at the end of the 1st
      leg of the short flights were equal to those at the end of the long flight and
      were much higher than those at the parallel time point in the long flight. In the
      short flight, craving levels at the beginning of the 2nd leg dropped relative to
      the end of the 1st leg, both for participants who smoked during the intermission
      and for those who did not, though the drop was steeper for the former. The
      results provide additional evidence for the role of psychological factors in
      determining the craving to smoke in a naturalistic setting.

PMID- 20141263
TI  - The dissemination and implementation of evidence-based psychological treatments.
      A review of current efforts.
AB  - Recognizing an urgent need for increased access to evidenced-based psychological
      treatments, public health authorities have recently allocated over $2 billion to
      better disseminate these interventions. In response, implementation of these
      programs has begun, some of it on a very large scale, with substantial
      implications for the science and profession of psychology. But methods to
      transport treatments to service delivery settings have developed independently
      without strong evidence for, or even a consensus on, best practices for
      accomplishing this task or for measuring successful outcomes of training. This
      article reviews current leading efforts at the national, state, and individual
      treatment developer levels to integrate evidence-based interventions into service
      delivery settings. Programs are reviewed in the context of the accumulated wisdom
      of dissemination and implementation science and of methods for assessment of
      outcomes for training efforts. Recommendations for future implementation
      strategies will derive from evaluating outcomes of training procedures and
      developing a consensus on necessary training elements to be used in these
      efforts.

PMID- 20141264
TI  - A meta-systems approach to evidence-based practice for children and adolescents.
AB  - Improving outcomes for children and adolescents with mental health needs demands
      a broad meta-systemic orientation to overcome persistent problems in current
      service systems. Improving outcomes necessitates inclusion of current and
      emerging evidence about effective practices for the diverse population of youth
      and their families. Key components of the meta-system for children with emotional
      or behavioral needs include families, cultural norms and values, and service
      sectors such as schools, pediatric health centers, specialty mental health
      systems, juvenile justice systems, child protection services, and substance use
      treatment systems. We describe each component of the meta-system, noting
      challenges to the provision of evidence-based practice (EBP) and highlighting
      ways to optimize outcomes. Our focus is on the inclusion of evidence-based
      assessment and interventions, including prevention, within a developmentally
      driven and culturally responsive contextual model. Recommendations for addressing
      disparities in research funding and essential steps to foster communication and
      coordination of EBP across settings are provided.

PMID- 20141265
TI  - The efficacy of psychodynamic psychotherapy.
AB  - Empirical evidence supports the efficacy of psychodynamic therapy. Effect sizes
      for psychodynamic therapy are as large as those reported for other therapies that
      have been actively promoted as "empirically supported" and "evidence based." In
      addition, patients who receive psychodynamic therapy maintain therapeutic gains
      and appear to continue to improve after treatment ends. Finally, nonpsychodynamic
      therapies may be effective in part because the more skilled practitioners utilize
      techniques that have long been central to psychodynamic theory and practice. The
      perception that psychodynamic approaches lack empirical support does not accord
      with available scientific evidence and may reflect selective dissemination of
      research findings.

PMID- 20141266
TI  - Evolutionary psychology. Controversies, questions, prospects, and limitations.
AB  - Evolutionary psychology has emerged over the past 15 years as a major theoretical
      perspective, generating an increasing volume of empirical studies and assuming a
      larger presence within psychological science. At the same time, it has generated
      critiques and remains controversial among some psychologists. Some of the
      controversy stems from hypotheses that go against traditional psychological
      theories; some from empirical findings that may have disturbing implications;
      some from misunderstandings about the logic of evolutionary psychology; and some
      from reasonable scientific concerns about its underlying framework. This article
      identifies some of the most common concerns and attempts to elucidate
      evolutionary psychology's stance pertaining to them. These include issues of
      testability and falsifiability; the domain specificity versus domain generality
      of psychological mechanisms; the role of novel environments as they interact with
      evolved psychological circuits; the role of genes in the conceptual structure of
      evolutionary psychology; the roles of learning, socialization, and culture in
      evolutionary psychology; and the practical value of applied evolutionary
      psychology. The article concludes with a discussion of the limitations of current
      evolutionary psychology.

PMID- 20141267
TI  - Edith Kaplan (1924-2009).
AB  - This article honors the life accomplishments of Edith Kaplan. She is widely
      regarded as the mother of clinical neuropsychology; she passed away on September
      3, 2009, at the age of 85. Her modifications to the original Wechsler Adult
      Intelligence Scale (WAIS) and Wechsler Memory Scale led to the development of a
      new school of clinical neuropsychology known as "the process approach," of which
      Kaplan is unequivocally regarded as the pioneer and chief architect. She is best
      known for her work in test development, and she is the lead or senior author on
      numerous assessment instruments designed for both children and adults that are
      used nationally and internationally. At the time of her death, Kaplan was working
      as a professor of psychology at Suffolk University, an adjunct professor of
      neurology and psychiatry at Boston University School of Medicine, and an
      affiliate professor of psychology at Clark University. And, of great importance
      to the field, she continued to be vigorously involved in her most beloved
      activity of all, teaching students about neuropsychology.

PMID- 20141268
TI  - Imagined interactions.

PMID- 20141269
TI  - Back in the real world.

PMID- 20141270
TI  - Reasons for skepticism about the efficacy of simulated social contact
      interventions.

PMID- 20141272
TI  - Intergenerational effects of high neuroticism in parents and their public health
      significance.

PMID- 20141273
TI  - Prescriptive authority in the face of research revelations.

PMID- 20141275
TI  - Concurrent discrimination learning in Parkinson's disease.
AB  - Studies of neuropsychological patients and experimental animals have demonstrated
      that the striatum plays a role in implicit habit learning. Here, we examined the
      performance of patients with Parkinson's disease (PD) on a concurrent
      discrimination task that can be learned implicitly by neurologically intact
      individuals. Participants viewed a pair of shapes on each trial and, under a
      timed deadline, guessed which one concealed a smiling face. About half the
      control participants exhibited minimal awareness of the cue-reward relationships
      as assessed by a post-test evaluation. Nevertheless, these participants were able
      to perform the discrimination task; there was no correlation between awareness
      and performance on the task. In contrast, minimally aware patients with PD showed
      no learning, whereas those who were more aware of the relationships performed as
      well as control participants on the task. There was a significant correlation
      between awareness and performance in patients with PD. These data support the
      idea that the basal ganglia play a role in implicit habit learning and underscore
      the importance of using tests of awareness to assess the content and process of
      learning in humans.

PMID- 20141276
TI  - Amygdala-dependent fear conditioning in humans is modulated by the BDNFval66met
      polymorphism.
AB  - The brain-derived neurotrophic factor (BDNF) is critically involved in
      neuroplasticity, as well as the acquisition, consolidation, and retention of
      hippocampal- and amygdala-dependent learning. A common functional A-->G single
      nucleotide polymorphism (BDNFval66met) in the prodomain of the human BDNF gene is
      associated with abnormal intracellular trafficking and reduced activity-dependent
      BDNF release. We studied the effect of BDNFval66met in an aversive differential
      fear conditioning, and a delayed extinction paradigm in 57 healthy participants.
      Pictures of male faces were used as stimuli and fear learning was quantified by
      fear potentiated startle (FPS) and skin conductance responses (SCR). Aware BDNF
      met-carriers show a deficit in amygdala-dependent fear conditioning as indicated
      by an absence of FPS responses in the last acquisition block. This deficit was
      maintained in the first block of extinction. No genotype differences were found
      in conditioned SCR discrimination. These data provide evidence for the
      involvement of BDNF signaling in human amygdala-dependent learning. We suggest
      that the BDNF met-allele may have a protective effect for the development of
      affective pathologies that may be mediated via reduced synaptic plasticity
      induced by negative experience.

PMID- 20141277
TI  - Adolescents exhibit behavioral differences from adults during instrumental
      learning and extinction.
AB  - Adolescence is associated with the development of brain regions linked to
      cognition and emotion. Such changes are thought to contribute to the behavioral
      and neuropsychiatric vulnerabilities of this period. We compared adolescent
      (Postnatal Days 28-42) and adult (Postnatal Day 60+) rats as they performed a
      simple instrumental task and extinction. Rats were trained to poke into a hole
      for a food-pellet reinforcer. After six days of training, rats underwent
      extinction sessions in which the previously rewarded behavior was no longer
      reinforced. During extinction, we examined the effects of continued presentation
      of a cue light and food restriction. Adults and adolescents exhibited similar
      performance during training, although adolescents made more task-irrelevant
      pokes, consistent with increased exploration. Adults made more premature pokes,
      which could indicate a more exclusive focus on the task. During extinction,
      adolescents made more perseverative (previously reinforced) pokes than adults.
      This behavior was strongly modulated by the combination of motivational factors
      present (food restriction and cue light), indicating that adolescents were
      differentially sensitive to them. Furthermore, food restriction induced greater
      open-field activity in adolescents but not in adults. Thus, as the neural
      circuitry of motivated behavior develops substantially during adolescence, so too
      does the behavioral sensitivity to motivational factors. Understanding how such
      factors differently affect adolescents may shed light on mechanisms that lead to
      the development of disorders that are manifested during this period.

PMID- 20141278
TI  - The role of the nucleus accumbens core in impulsive choice, timing, and reward
      processing.
AB  - The present series of experiments aimed to pinpoint the source of nucleus
      accumbens core (AcbC) effects on delay discounting. Rats were trained with an
      impulsive choice procedure between an adjusting smaller sooner reward and a fixed
      larger later reward. The AcbC-lesioned rats produced appropriate choice behavior
      when the reward magnitude was equal. An increase in reward magnitude resulted in
      a failure to increase preference for the larger later reward in the AcbC-lesioned
      rats, whereas a decrease in the larger later reward duration resulted in normal
      alterations in choice behavior in AcbC-lesioned rats. Subsequent experiments with
      a peak timing (Experiments 2 and 3) and a behavioral contrast (Experiment 4)
      indicated that the AcbC-lesioned rats suffered from decreased incentive
      motivation during changes in reward magnitude (Experiments 2 and 4) and when
      expected rewards were omitted (Experiments 2 and 3), but displayed intact
      anticipatory timing of reward delays (Experiments 2 and 3). The results indicate
      that the nucleus accumbens core is critical for determining the incentive value
      of rewards, but does not participate in the timing of reward delays.

PMID- 20141279
TI  - Intra-accumbens infusion of a muscarinic antagonist reduces food intake without
      altering the incentive properties of food-associated cues.
AB  - Previous work has implicated the cholinergic system in modulating feeding
      behavior; however, its specific function remains unclear. This work aims to
      characterize potential dissociations between the central cholinergic modulation
      of the incentive properties of food and food-associated cues, and consummatory
      behaviors. Three separate experiments demonstrated that intra-accumbens infusion
      of the muscarinic antagonist scopolamine 3 hr before the testing session
      significantly decreased food intake. General motor activity in anticipation of
      food was not diminished. Experiments also showed that scopolamine did not impair
      operant responding for a food-associated conditioned reinforcer (CR), nor was d
      amphetamine potentiation of CR responding altered by scopolamine pretreatment.
      This study contributes to the growing evidence that goal-seeking behaviors are
      mediated by a set of neural processes distinct from those governing food reward.

PMID- 20141280
TI  - Lesions of the rat perirhinal cortex spare the acquisition of a complex
      configural visual discrimination yet impair object recognition.
AB  - Rats with perirhinal cortex lesions were sequentially trained in a rectangular
      water tank on a series of 3 visual discriminations, each between mirror-imaged
      stimuli. When these same discriminations were tested concurrently, the rats were
      forced to use a configural strategy to solve the problems effectively. There was
      no evidence that lesions of the perirhinal cortex disrupted the ability to learn
      the concurrent configural discrimination task, which required the rats to learn
      the precise combination of stimulus identity with stimulus placement
      ("structural" learning). The same rats with perirhinal cortex lesions were also
      unimpaired on a test of spatial working memory (reinforced T maze alternation),
      although they were markedly impaired on a new test of spontaneous object
      recognition. For the recognition test, rats received multiple trials within a
      single session in which on every trial, they were allowed to explore 2 objects, 1
      familiar, the other novel. On the basis of their differential exploration times,
      rats with perirhinal cortex lesions showed very poor discrimination of the novel
      objects, thereby confirming the effectiveness of the surgery. The discovery that
      bilateral lesions of the perirhinal cortex can leave configural (structural)
      learning seemingly unaffected points to a need to refine those models of
      perirhinal cortex function that emphasize its role in representing conjunctions
      of stimulus features.

PMID- 20141281
TI  - Brainstem and hypothalamic regulation of sleep pressure and rebound in newborn
      rats.
AB  - Sleep pressure and rebound comprise the two compensatory or "homeostatic"
      responses to sleep deprivation. Although sleep pressure is expressed by infant
      rats as early as postnatal day (P)5, sleep rebound does not appear to emerge
      until after P11. We reexamined the developmental expression of these sleep
      regulatory processes in P2 and P8 rats by depriving them of sleep for 30 min
      using a cold, arousing stimulus delivered to a cold-sensitive region of the
      snout. This method effectively increased sleep pressure over the 30-min period
      (i.e., increases in the number of arousing stimuli presented over time).
      Moreover, sleep rebound (i.e., increased sleep during the recovery period) is
      demonstrated for the first time at these ages. Next, we showed that precollicular
      transections in P2 rats prevent sleep rebound without affecting sleep pressure,
      suggesting that the brainstem is sufficient to support sleep pressure, but sleep
      rebound depends on neural mechanisms that lie rostral to the transection.
      Finally, again in P2 rats, we used c-fos immunohistochemistry to examine neural
      activation throughout the neuraxis during sleep deprivation and recovery. Sleep
      deprivation and rebound were accompanied by significant increases in neural
      activation in both brainstem and hypothalamic nuclei, including the ventrolateral
      preoptic area and median preoptic nucleus. This early developmental expression of
      sleep pressure and rebound and the apparent involvement of brainstem and
      hypothalamic structures in their expression further solidify the notion that
      sleep-wake processes in newborns-defined at these ages without reference to state
      dependent EEG activity-provide the foundation on which the more familiar
      processes of adults are built.

PMID- 20141282
TI  - Increased GABAergic activity in the region of the pedunculopontine and deep
      mesencephalic reticular nuclei reduces REM sleep and impairs learning in rats.
AB  - Newly formed memories are initially fragile and require consolidation to be
      transformed into an enduring state. Memory consolidation may occur during
      increased postlearning REM sleep. REM deprivation during these periods (termed
      REM sleep windows [RSWs]) impairs subsequent performance. The pedunculopontine
      nucleus (PPT) and adjacent deep mesencephalic reticular nuclei (DpMe) have been
      implicated in the generation of REM sleep. Following 24-hr baseline recording,
      rats were trained on the 2-way avoidance task for 50 trials/day over 2 days and
      retested on Day 3. EEG was recorded 22 hr after training on training Days 1 and
      2. Rats were injected with the GABAB agonist baclofen or saline into the PPT/DpMe
      region at 0300 to coincide with the start of a known RSW. Based on shuttle
      performance, saline rats were assigned post hoc to a learning group (LG) that
      avoided the footshock at least 60% at retest or nonlearning group (NLG) that
      performed below this criterion. Baclofen-injected rats were not assigned post hoc
      into separate groups as all rats performed below the learning criterion. PPN/DpMe
      infusions of the inhibitory GABAB agonist baclofen decreased REM and impaired
      subsequent memory performance. Normal GABAergic transmission in the PPN/DpMe may
      be necessary for REM to occur and for the consolidation of incentive learning.

PMID- 20141283
TI  - Dynamic interactions between coupled oscillators within the hamster circadian
      pacemaker.
AB  - Within the mammalian suprachiasmatic nucleus, multiple oscillators interact to
      coordinate circadian rhythms in behavior and physiology. We have developed a
      behavioral assay that disassociates central oscillators and allows rigorous study
      of their formal properties and interactions. Rodents held under 24h
      light:dark:light:dark (LDLD) cycles display "split" activity rhythms that reflect
      the reorganization of the central pacemaker into two oscillator groups cycling
      ~12h apart. After transfer to constant conditions, the two activity components
      rejoin through a series of transients lasting 2-7 days. Here we analyze fusion
      dynamics, characterize the underlying oscillator interactions, and assess two
      influencing factors: phase of transfer and lighting conditions upon transfer.
      Syrian hamsters were split under LDLD with dimly lit nights and then transferred
      to constant dim illumination or complete darkness during one of the two daily
      scotophases. Fusion was influenced by phase of transfer, suggesting that the
      oscillators split under LDLD exert an asymmetric influence over one another.
      Transfer to constant dim and dark conditions produced similar overall patterns of
      fusion, but nevertheless differed in the rejoined state of the system. The
      present results are discussed within a model wherein oscillators influence one
      another in a phase-dependent manner.

PMID- 20141284
TI  - Hippocampal lesions impair retention of discriminative responding based on energy
      state cues.
AB  - The present research investigated the hypothesis that the hippocampus is involved
      with the control of appetitive behavior by interoceptive "hunger" and "satiety"
      signals. Rats were trained to solve a food deprivation intensity discrimination
      problem in which stimuli produced by 0-hr and 24-hr food deprivation served as
      discriminative cues for the delivery of sucrose pellets. For Group 0+, sucrose
      pellets were delivered at the conclusion of each 4-min session that took place
      under 0-hr food deprivation, whereas no pellets were delivered during sessions
      that took place when the rats had been food deprived for 24 hr. Group 24+
      received the reverse discriminative contingency (i.e., they received sucrose
      pellets under 24-hr but not under 0-hr food deprivation). When asymptotic
      discrimination performance was achieved (indexed by greater incidence of food
      magazine approach behavior on reinforced compared with nonreinforced sessions),
      half of the rats in each group received hippocampal lesions, and the remaining
      rats in each group were designated as sham- or nonlesioned controls. Following
      recovery from surgery, food deprivation discrimination performance was compared
      for lesioned and control rats in both Groups 0+ and 24+. Discriminative
      responding was impaired for rats with hippocampal lesions relative to their
      controls. This impairment was based largely on elevated responding to
      nonreinforced food deprivation cues. In addition, hippocampal damage was
      associated with increased body weight under conditions of ad libitum feeding. The
      results suggest that the inhibition of appetitive behavior by energy state
      signals may depend, in part, on the hippocampus.

PMID- 20141285
TI  - Caloric restriction alters seizure disposition and behavioral profiles in seizure
      prone (fast) versus seizure-resistant (slow) rats.
AB  - Caloric restriction (CR), primarily known for extending life span, has proven
      anticonvulsant in several seizure models and antiepileptogenic in a strain of
      inherently seizure susceptible mice. Our animal model consisted of a seizure
      prone (Fast) strain that naturally exhibits attention-deficit/hyperactivity
      disorder (ADHD)-like behaviors and a comparison seizure-resistant (Slow) strain;
      we evaluated CR's effect on the typical seizure sensitivities and behavioral
      profiles of each strain. Fast and Slow rats were fed ad libitum or were
      calorically restricted to 80% of free-feeding body weight. Rats were then tested
      in the open field (hyperactivity), Morris water maze (learning and attention),
      and restraint (impulsivity) paradigms and finally kindled from the amygdala.
      Ultimately, CR abolished signs of abnormal hyperactivity in the Fast strain and
      retarded their kindling rates, making it the first manipulation to demonstrate an
      antiepileptogenic effect in this animal model. CR also shortened seizure
      durations in fully kindled Slow rats but had no effect on their kindling rates,
      implying a differential effect of CR on genotype. These results clearly endorse
      further investigation into the potential benefits of CR for both epilepsy and
      ADHD.

PMID- 20141286
TI  - Dietary cholesterol impairs memory and memory increases brain cholesterol and
      sulfatide levels.
AB  - Cholesterol and sulfatides play many important roles in learning and memory. To
      date, our observations about the effects of cholesterol on learning have been
      assessed during response acquisition; that is, the learning of a new memory.
      Here, we report for the first time to our knowledge, on the effect of a
      cholesterol diet on a previously formed memory. Rabbits were given trace
      conditioning of the nictitating membrane response for 10 days, then fed a 2%
      cholesterol diet for 8 weeks, and then assessed for memory recall of the
      initially learned task. We show that dietary cholesterol had an adverse effect on
      memory recall. Second, we investigated whether dietary cholesterol caused an
      increase in brain cholesterol and sulfatide levels in four major brain structures
      (hippocampus, frontal lobe, brainstem, and cerebellum) using a technique for
      analyzing myelin and myelin-free fractions separately. Although our data confirm
      previous findings that dietary cholesterol does not directly affect cholesterol
      and establish that it does not affect sulfatide levels in the brain, these levels
      did increase rather significantly in the hippocampus and frontal lobe as a
      function of learning and memory.

PMID- 20141287
TI  - The "good" limb makes the "bad" limb worse: experience-dependent interhemispheric
      disruption of functional outcome after cortical infarcts in rats.
AB  - Following stroke-like lesions to the sensorimotor cortex in rats, experience with
      the ipsi-to-lesion (ipsilesional), "nonparetic", forelimb worsens deficits in the
      contralesional, "paretic", forelimb. We tested whether the maladaptive effects of
      experience with the nonparetic limb are mediated through callosal connections and
      the contralesional sensorimotor cortex. Adult male rats with proficiency in
      skilled reaching with their dominant (for reaching) forelimb received ischemic
      bilateral sensorimotor cortex lesions, or unilateral lesions, with or without
      callosal transections. After assessing dominant forelimb function (the paretic
      forelimb in rats with unilateral lesions), animals were trained with their
      nonparetic/nondominant forelimb or underwent control procedures for 15 days.
      Animals were then tested with their paretic/dominant forelimb. In animals with
      unilateral lesions only, nonparetic forelimb training worsened subsequent
      performance with the paretic forelimb, as found previously. This effect was not
      found in animals with both callosal transections and unilateral lesions. After
      bilateral lesions, training the nondominant limb did not worsen function of the
      dominant limb compared with controls. Thus, the maladaptive effects of training
      the nonparetic limb on paretic forelimb function depend upon the contralesional
      cortex and transcallosal projections. This suggests that this experience
      dependent disruption of functional recovery is mediated through interhemispheric
      connections of the sensorimotor cortex.

PMID- 20141288
TI  - Age-associated improvements in cross-modal prepulse inhibition in mice.
AB  - Prepulse inhibition (PPI) is an operational measure of sensorimotor gating that
      is thought to probe preattentional filtering mechanisms. PPI is deficient in
      several neuropsychiatric disorders, possibly reflecting abnormalities in frontal
      cortical-striatal circuitry. Several studies support the predictive validity of
      animal PPI to model human sensorimotor gating phenomena but only limited studies
      have addressed the effects of aging. Studies in humans suggest that PPI is
      improved or unaffected as humans age (>60 years) and does not correlate with
      cognitive decline in aged populations. Rodent studies to date, however, suggest
      that PPI declines with age. Here we tested the hypothesis that PPI measures in
      rodents are sensitive to stimulus modality, with the prediction that intact
      sensory modalities in aged animals would be predictive of aging-induced increases
      in PPI. To test our hypothesis, we assessed PPI using acoustic, tactile, and
      visual prepulses in young (4 month) and old (23 month) C57BL/6N mice. Consistent
      with data across species, we observed reduced startle reactivity in older mice.
      Aging effects on PPI interacted significantly with prepulse modality, with
      deficient acoustic PPI but increased visual and tactile PPI in aged animals.
      These data are therefore consistent with PPI studies in older humans when
      controlling for hearing impairments. The results are discussed in terms of 1)
      cross-species translational validity for mouse PPI testing, 2) the need for
      startle reactivity differences to be accounted for in PPI analyses, and 3) the
      utility of cross-modal PPI testing in subjects where hearing loss has been
      documented.

PMID- 20141289
TI  - Competition between novelty and cocaine conditioned reward is sensitive to drug
      dose and retention interval.
AB  - The conditioned rewarding effects of novelty compete with those of cocaine for
      control over choice behavior using a place conditioning task. The purpose of the
      present study was to use multiple doses of cocaine to determine the extent of
      this competition and to determine whether novelty's impact on cocaine reward was
      maintained over an abstinence period. In Experiment 1, rats were conditioned with
      cocaine (7.5, 20, or 30 mg/kg ip) to prefer one side of an unbiased place
      conditioning apparatus relative to the other. In a subsequent phase, all rats
      received alternating daily confinements to the previously cocaine paired and
      unpaired sides of the apparatus. During this phase, half the rats had access to a
      novel object on their initially unpaired side; the remaining rats did not receive
      objects. The ability of novelty to compete with cocaine in a drug free and
      cocaine challenge test was sensitive to cocaine dose. In Experiment 2, a place
      preference was established with 10 mg/kg cocaine and testing occurred after 1,
      14, or 28 day retention intervals. Findings indicate that choice behaviors
      mediated by cocaine conditioning are reduced with the passing of time. Taken
      together, competition between cocaine and novelty conditioned rewards are
      sensitive to drug dose and retention interval.

PMID- 20141290
TI  - Time-based prospective memory impairment in patients with thalamic stroke.
AB  - The role of the thalamus in memory is potentially very complex. However, most
      studies on the memory impairments of thalamic lesions have focused on
      retrospective memory, rarely on prospective memory. To explore the effect of
      thalamic lesions on event-based prospective memory (EBPM) and time-based
      prospective memory (TBPM), respectively, and to verify the hypothesis that the
      thalamus is involved in the prospective memory, EBPM and TBPM tasks were
      administered to 18 thalamic stroke patients and 18 age- and education-matched
      healthy controls. In the EBPM task, subjects were asked to perform an action
      whenever particular words were presented. In the TBPM task, subjects were asked
      to perform an action at certain times. Compared with the performance of healthy
      controls on EBPM and TBPM tasks (EBPM, 4.3 +/- 1.5; TBPM, 5.4 +/- 1.0), there was
      a significant difference in the performance of thalamic stroke patients in the
      TBPM tasks (2.4 +/- 1.6), but no difference was found in EBPM tasks (3.7 +/-
      1.1). These results may indicate that the thalamus is involved in PM and
      particularly in TBPM.

PMID- 20141291
TI  - Central vasopressin V1a receptor activation is independently necessary for both
      partner preference formation and expression in socially monogamous male prairie
      voles.
AB  - The neuropeptide arginine vasopressin (AVP) modulates a variety of species
      specific social behaviors. In socially monogamous male prairie voles, AVP acts
      centrally via vasopressin V1a receptor (V1aR) to facilitate mating induced
      partner preferences. The display of a partner preference requires at least 2
      temporally distinct processes: social bond formation as well as its recall, or
      expression. Studies to date have not determined in which of these processes V1aR
      acts to promote partner preferences. Here, male prairie voles were administered
      intracerebroventricularly a V1aR antagonist (AVPA) at different time points to
      investigate the role of V1aR in social bond formation and expression. Animals
      receiving AVPA prior to cohabitation with mating or immediately prior to partner
      preference testing failed to display a partner preference, while animals
      receiving AVPA immediately after cohabitation with mating and control animals
      receiving vehicle at all 3 time points displayed partner preferences. These
      results suggest that V1aR signaling is necessary for both the formation and
      expression of partner preferences and that these processes are dissociable.

PMID- 20141293
TI  - Electroconvulsive shocks exacerbate the heightened acoustic startle response in
      stressed rats.
AB  - Electroconvulsive therapy (ECT) has been successfully used in the treatment of
      depression, particularly when the illness is refractory to pharmacological
      therapy. A recent study has shown that ECT is also effective in reducing both
      depressive and posttraumatic stress disorder (PTSD) symptoms in patients with
      major depression (MDD) and co-occurring PTSD. This raises the possibility that
      ECT might be effective in the treatment of PTSD, a disease whose prevalence has
      increased substantially in recent years. A characteristic symptom of PTSD is an
      exaggerated reactivity to startling sounds (acoustic startle response; ASR). In
      the present study, we investigated the effects of electroconvulsive shocks (ECS)
      on the ASR, in a rat model of traumatic stress. The animals were subjected to a
      restraint/tailshock paradigm and then administered ECS. ASR measurements were
      obtained at several time points following ECS administration. Although ECS had no
      effect in control rats, it significantly exacerbated the already potentiated ASR
      in the stressed group. While ECT may prove to be an effective treatment for
      certain symptoms of co-occurring MDD/PTSD or PTSD alone, it may exacerbate
      heightened arousal associated with PTSD.

PMID- 20141292
TI  - Evidence for the use of an internal sense of direction in homing.
AB  - Path integration, the ability to maintain a representation of location and
      direction on the basis of internal cues, is thought to be important for
      navigation and the learning of spatial relationships. Representations of location
      and direction in the brain, such as head direction cells, grid cells, and place
      cells in the limbic system, are thought to underlie navigation by path
      integration. While this idea is generally consistent with lesion studies, the
      relationship between such neural activity and behavior has not been studied on a
      task where animals demonstrably use a path integration strategy. Here we report
      the development of such a task in rats: by slowly rotating rats before their
      return to a trial-unique home base, we could show subjects relied on internal
      cues only to navigate. To illustrate how this task can be combined with
      recording, we show examples of simultaneously recorded head direction cells in
      which neural activity is closely related to rats' homing direction. These results
      support the notion that rats can navigate by path integration, that this ability
      depends on head direction cells, and suggest a convenient behavioral paradigm for
      investigating the neural basis of navigation.

PMID- 20141294
TI  - The sleep-like nature of early mammalian behavioral rhythms: Theoretical comment
      on Todd et al. (2010).
AB  - Early sleep patterns lack several of the major defining physiological criteria
      used to identify sleep states in adult animals, but many typical aspects of
      mature sleep can nevertheless be demonstrated at surprisingly early stages of
      development. In Todd, Gibson, Shaw, & Blumberg (2010), the ability to compensate
      for enforced sleep deprivation is found to be present already shortly after birth
      in laboratory rats, an altricial mammalian species. Whereas the brainstem is
      capable of resisting enforced wakefulness by an increasing "pressure" to fall
      asleep, "catch-up" replacement of the lost sleep by means of longer subsequent
      sleep durations requires forebrain participation. This investigation represents
      an initial foray into the theoretically important area of the ontogeny of
      homeostatic regulatory mechanisms for behaviorally crucial neurophysiological
      processes.

PMID- 20141295
TI  - Mindfulness and psychological process.
AB  - The author reviews the articles in the Special Section on Mindfulness, starting
      from the assumption that emotions evolved as signaling systems that need to be
      sensitive to environmental contingencies. Failure to switch off emotion is due to
      the activation of mental representations of present, past, and future that are
      created independently of external contingencies. Mindfulness training can be seen
      as one way to teach people to discriminate such "simulations" from objects and
      contingencies as they actually are. The articles in this Special Section show how
      even brief laboratory training can have effects on processing affective stimuli;
      that long-term meditation practitioners show distinct reactions to pain; that
      longer meditation training is associated with differences in brain structure;
      that 8 weeks' mindfulness practice brings about changes in the way emotion is
      processed showing that participants can learn to uncouple the sensory, directly
      experienced self from the "narrative" self; that mindfulness training can affect
      working memory capacity, and enhance the ability of participants to talk about
      past crises in a way that enables them to remain specific and yet not be
      overwhelmed. The implications of these findings for understanding emotion and for
      further research is discussed.

PMID- 20141297
TI  - Empirical explorations of mindfulness: conceptual and methodological conundrums.
AB  - This commentary reflects on the articles in this Special Issue. The appearance of
      this group of articles underscores the important idea that a major target of
      mindfulness practice is on emotion. Transformation in trait affect is a key goal
      of all contemplative traditions. This commentary addresses several key
      methodological and conceptual issues in the empirical study of mindfulness. The
      many ways in which the term "mindfulness" is used in the articles in this Special
      Issue are noted, and they include its reference to states, traits, and
      independent variables that are manipulated in an experimental context. How the
      term "mindfulness" is conceptualized and operationalized is crucial, and for
      progress to be made it is essential that we qualify the use of this term by
      reference to how it is being operationalized in each context. Other
      methodological issues are considered, such as the duration of training and how it
      should be measured, and the nature of control and comparison groups in studies of
      mindfulness-based interventions. Finally, the commentary ends with a
      consideration of the targets within emotion processing that are likely to be
      impacted by mindfulness. This collection of articles underscores the substantial
      progress that has occurred in the empirical study of mindfulness and it is a
      harbinger of a very promising future in this area.

PMID- 20141298
TI  - Dispositional mindfulness and depressive symptomatology: correlations with limbic
      and self-referential neural activity during rest.
AB  - To better understand the relationship between mindfulness and depression, we
      studied normal young adults (n = 27) who completed measures of dispositional
      mindfulness and depressive symptomatology, which were then correlated with (a)
      rest: resting neural activity during passive viewing of a fixation cross,
      relative to a simple goal-directed task (shape-matching); and (b) reactivity:
      neural reactivity during viewing of negative emotional faces, relative to the
      same shape-matching task. Dispositional mindfulness was negatively correlated
      with resting activity in self-referential processing areas, whereas depressive
      symptomatology was positively correlated with resting activity in similar areas.
      In addition, dispositional mindfulness was negatively correlated with resting
      activity in the amygdala, bilaterally, whereas depressive symptomatology was
      positively correlated with activity in the right amygdala. Similarly, when
      viewing emotional faces, amygdala reactivity was positively correlated with
      depressive symptomatology and negatively correlated with dispositional
      mindfulness, an effect that was largely attributable to differences in resting
      activity. These findings indicate that mindfulness is associated with intrinsic
      neural activity and that changes in resting amygdala activity could be a
      potential mechanism by which mindfulness-based depression treatments elicit
      therapeutic improvement.

PMID- 20141299
TI  - Minding one's emotions: mindfulness training alters the neural expression of
      sadness.
AB  - Recovery from emotional challenge and increased tolerance of negative affect are
      both hallmarks of mental health. Mindfulness training (MT) has been shown to
      facilitate these outcomes, yet little is known about its mechanisms of action.
      The present study employed functional MRI (fMRI) to compare neural reactivity to
      sadness provocation in participants completing 8 weeks of MT and waitlisted
      controls. Sadness resulted in widespread recruitment of regions associated with
      self-referential processes along the cortical midline. Despite equivalent self
      reported sadness, MT participants demonstrated a distinct neural response, with
      greater right-lateralized recruitment, including visceral and somatosensory areas
      associated with body sensation. The greater somatic recruitment observed in the
      MT group during evoked sadness was associated with decreased depression scores.
      Restoring balance between affective and sensory neural networks-supporting
      conceptual and body based representations of emotion-could be one path through
      which mindfulness reduces vulnerability to dysphoric reactivity.

PMID- 20141300
TI  - Effects of mindfulness on meta-awareness and specificity of describing prodromal
      symptoms in suicidal depression.
AB  - The authors examined the effects of mindfulness training on 2 aspects of mode of
      processing in depressed participants: degree of meta-awareness and specificity of
      memory. Each of these has been suggested as a maladaptive aspect of a mode of
      processing linked to persistence and recurrence of symptoms. Twenty-seven
      depressed participants, all of whom had experienced suicidal crises, described
      warning signs for their last crisis. These descriptions were blind-rated
      independently for meta-awareness and specificity. Participants were then randomly
      allocated to receive mindfulness-based cognitive therapy (MBCT) plus treatment as
      usual (TAU) or TAU alone, and retested after 3 months. Results showed that,
      although comparable at baseline, patients randomized to MBCT displayed
      significant posttreatment differences in meta-awareness and specificity compared
      with TAU patients. These results suggest that mindfulness training may enable
      patients to reflect on memories of previous crises in a detailed and decentered
      way, allowing them to relate to such experiences in a way that is likely to be
      helpful in preventing future relapses.

PMID- 20141301
TI  - Cortical thickness and pain sensitivity in zen meditators.
AB  - Zen meditation has been associated with low sensitivity on both the affective and
      the sensory dimensions of pain. Given reports of gray matter differences in
      meditators as well as between chronic pain patients and controls, the present
      study investigated whether differences in brain morphometry are associated with
      the low pain sensitivity observed in Zen practitioners. Structural MRI scans were
      performed and the temperature required to produce moderate pain was assessed in
      17 meditators and 18 controls. Meditators had significantly lower pain
      sensitivity than controls. Assessed across all subjects, lower pain sensitivity
      was associated with thicker cortex in affective, pain-related brain regions
      including the anterior cingulate cortex, bilateral parahippocampal gyrus and
      anterior insula. Comparing groups, meditators were found to have thicker cortex
      in the dorsal anterior cingulate and bilaterally in secondary somatosensory
      cortex. More years of meditation experience was associated with thicker gray
      matter in the anterior cingulate, and hours of experience predicted more gray
      matter bilaterally in the lower leg area of the primary somatosensory cortex as
      well as the hand area in the right hemisphere. Results generally suggest that
      pain sensitivity is related to cortical thickness in pain-related brain regions
      and that the lower sensitivity observed in meditators may be the product of
      alterations to brain morphometry from long-term practice.

PMID- 20141302
TI  - Examining the protective effects of mindfulness training on working memory
      capacity and affective experience.
AB  - We investigated the impact of mindfulness training (MT) on working memory
      capacity (WMC) and affective experience. WMC is used in managing cognitive
      demands and regulating emotions. Yet, persistent and intensive demands, such as
      those experienced during high-stress intervals, may deplete WMC and lead to
      cognitive failures and emotional disturbances. We hypothesized that MT may
      mitigate these deleterious effects by bolstering WMC. We recruited 2 military
      cohorts during the high-stress predeployment interval and provided MT to 1 (MT, n
      = 31) but not the other group (military control group, MC, n = 17). The MT group
      attended an 8-week MT course and logged the amount of out-of-class time spent
      practicing formal MT exercises. The operation span task was used to index WMC at
      2 testing sessions before and after the MT course. Although WMC remained stable
      over time in civilians (n = 12), it degraded in the MC group. In the MT group,
      WMC decreased over time in those with low MT practice time, but increased in
      those with high practice time. Higher MT practice time also corresponded to lower
      levels of negative affect and higher levels of positive affect (indexed by the
      Positive and Negative Affect Schedule). The relationship between practice time
      and negative, but not positive, affect was mediated by WMC, indicating that MT
      related improvements in WMC may support some but not all of MT's salutary
      effects. Nonetheless, these findings suggest that sufficient MT practice may
      protect against functional impairments associated with high-stress contexts.

PMID- 20141303
TI  - Differential effects on pain intensity and unpleasantness of two meditation
      practices.
AB  - Pain is an unpleasant sensory and emotional experience that can be regulated by
      many different cognitive mechanisms. We compared the regulatory qualities of two
      different meditation practices during noxious thermal stimuli: Focused Attention,
      directed at a fixation cross away from the stimulation, which could regulate
      negative affect through a sensory gating mechanism; and Open Monitoring, which
      could regulate negative affect through a mechanism of nonjudgmental, nonreactive
      awareness of sensory experience. Here, we report behavioral data from a
      comparison between novice and long-term meditation practitioners (long-term
      meditators, LTMs) using these techniques. LTMs, compared to novices, had a
      significant reduction of self-reported unpleasantness, but not intensity, of
      painful stimuli while practicing Open Monitoring. No significant effects were
      found for FA. This finding illuminates the possible regulatory mechanism of
      meditation-based clinical interventions like Mindfulness-Based Stress Reduction
      (MBSR). Implications are discussed in the broader context of training-induced
      changes in trait emotion regulation.

PMID- 20141304
TI  - A preliminary investigation of the effects of experimentally induced mindfulness
      on emotional responding to film clips.
AB  - Despite encouraging preliminary findings regarding the efficacy of mindfulness
      and acceptance-based treatments for a range of psychological presentations, we
      have yet to elucidate mechanisms of action within these treatments. One mechanism
      through which mindfulness may reduce psychological symptoms and promote
      functioning is enhancing emotional responding and regulation. In this study, we
      used multimodal assessment to examine the effects of a brief mindfulness
      intervention in a laboratory setting on emotional experiences and regulation in
      response to distressing, positive, and affectively mixed film clips. Although
      there were no condition (mindfulness vs. control) effects on reports of emotional
      response or difficulties in regulation after the distressing film clip,
      participants in the mindfulness condition reported significantly greater positive
      affect in response to the positive film. Additionally, participants in the
      mindfulness condition reported more adaptive regulation (approaching
      significance, medium to large effect size) in response to the affectively mixed
      clip and significantly less negative affect immediately after this clip, although
      not after a recovery period. No significant differences emerged between
      conditions on physiological measures (skin conductance and heart rate) throughout
      the study.

PMID- 20141305
TI  - Effects of mindfulness-based stress reduction (MBSR) on emotion regulation in
      social anxiety disorder.
AB  - Mindfulness-based stress reduction (MBSR) is an established program shown to
      reduce symptoms of stress, anxiety, and depression. MBSR is believed to alter
      emotional responding by modifying cognitive-affective processes. Given that
      social anxiety disorder (SAD) is characterized by emotional and attentional
      biases as well as distorted negative self-beliefs, we examined MBSR-related
      changes in the brain-behavior indices of emotional reactivity and regulation of
      negative self-beliefs in patients with SAD. Sixteen patients underwent functional
      MRI while reacting to negative self-beliefs and while regulating negative
      emotions using 2 types of attention deployment emotion regulation-breath-focused
      attention and distraction-focused attention. Post-MBSR, 14 patients completed
      neuroimaging assessments. Compared with baseline, MBSR completers showed
      improvement in anxiety and depression symptoms and self-esteem. During the breath
      focused attention task (but not the distraction-focused attention task), they
      also showed (a) decreased negative emotion experience, (b) reduced amygdala
      activity, and (c) increased activity in brain regions implicated in attentional
      deployment. MBSR training in patients with SAD may reduce emotional reactivity
      while enhancing emotion regulation. These changes might facilitate reduction in
      SAD-related avoidance behaviors, clinical symptoms, and automatic emotional
      reactivity to negative self-beliefs in adults with SAD.

PMID- 20141306
TI  - Expressive flexibility.
AB  - Previous research has examined the consequences of either expressing or
      suppressing emotion using between-subjects designs. However, emotion theorists
      have argued that adaptation depends not so much on one regulatory process but
      rather on the ability to flexibly regulate emotion in accord with situational
      demands. To test this idea, Bonanno, Papa, Lalande, Westphal, and Coifman (2004)
      developed a within-subjects experimental paradigm to measure expressive
      flexibility (EF) and showed that EF predicted better self-reported adjustment
      over a 2-year period. The current investigation extends this research by (1)
      demonstrating the stability of EF across a 3-year period, (2) replicating the
      association between EF and positive adjustment using a more objective measure of
      adjustment (obtained from participants' close friends rather than based on self
      report), and (3) by showing that the positive relation between EF and adjustment
      was particularly salient in the context of high levels of cumulative life stress
      when EF was measured under conditions of immediate threat (presence of a
      subliminal threat prime).

PMID- 20141308
TI  - Psychometric properties of a computerized mobile phone method for assessing mood
      in daily life.
AB  - Ecological momentary assessment is a method that is now largely used to study
      behavior and mood in the settings in which they naturally occur. It maximizes
      ecological validity and avoids the limitations of retrospective self-reports.
      Studies on the psychometric properties of scales administered via mobile phone
      ecological momentary assessment are lacking. Therefore, we collected data on a 4
      item mood scale measuring well being on six occasions per day for 7 days (N =
      307) and examined compliance rate across time, within day, and within week. Using
      specific latent state-trait structural equation models, we analyzed the degree to
      which interindividual mood differences on an occasion of measurement were because
      of (a) measurement error, (b) stable differences in mood level, and (c) occasion
      specific differences. Results show good compliance (mean compliance: 74.9% of
      calls answered). Moreover, the scale showed good reliability (M = .82). Mood was
      mostly stable, especially the first 3 days of the week. It depended weakly albeit
      significantly on the previous assessment (autoregressive coefficient). In
      conclusion, computerized mobile phone assessment is an appropriate, easy-to-use,
      and promising method to measure mood.

PMID- 20141307
TI  - Dynamic infant-parent affect coupling during the face-to-face/still-face.
AB  - We examined dynamic infant-parent affect coupling using the Face-to-Face/Still
      Face (FFSF). The sample included 20 infants whose older siblings had been
      diagnosed with Autism Spectrum Disorders (ASD-sibs) and 18 infants with
      comparison siblings (COMP-sibs). A series of mixed effects bivariate
      autoregressive models was used to represent the self-regulation and interactive
      dynamics of infants and parents during the FFSF. Significant bidirectional
      affective coupling was found between infants and parents, with infant-to-parent
      coupling being more prominent than parent-to-infant coupling. Further analysis of
      within-dyad dynamics revealed ongoing changes in concurrent infant-parent
      linkages both within and between different FFSF episodes. The importance of
      considering both inter- and intradyad differences is discussed.

PMID- 20141309
TI  - Seeing, thinking, and feeling: emotion-regulating effects of gaze-directed
      cognitive reappraisal.
AB  - Cognitive reappraisal (CR) is an emotion-regulatory (ER) process that is
      theorized to operate via changes in appraisals. CR is distinct from attentional
      deployment (AD), an ER process that is theorized to operate via changes in
      attention. However, a recent neuroimaging study has suggested that the ER effects
      of CR might largely be explained by AD. In this study, I manipulated CR while
      holding visual AD constant across CR conditions. In a randomized within-subjects
      design, 54 participants used CR to increase and decrease emotion in response to
      unpleasant pictures. This was compared with simply viewing the pictures. On all
      trials, gaze was directed to a circumscribed area of the pictures. Even with gaze
      held constant across conditions, increase reappraisals led to higher ratings of
      emotional intensity, greater corrugator activity, and greater autonomic arousal.
      In addition, decrease reappraisals led to lower ratings of emotional intensity
      and lower corrugator activity, the latter of which held only when gaze was
      directed to arousing information. Overall, the results suggest that changes in
      appraisal are the likely mechanism for the ER effects of CR.

PMID- 20141310
TI  - The fearful-face advantage is modulated by task demands: evidence from the
      attentional blink.
AB  - Fearful faces receive privileged access to awareness relative to happy and
      nonemotional faces. We investigated whether this advantage depends on currently
      available attentional resources. In an attentional blink paradigm, observers
      detected faces presented during the attentional blink period that could depict
      either a fearful or a happy expression. Perceptual load of the blink-inducing
      target was manipulated by increasing flanker interference. For the low-load
      condition, fearful faces were detected more often than happy faces, replicating
      previous reports. More important, this advantage for fearful faces disappeared
      for the high-load condition, during which fearful and happy faces were detected
      equally often. These results suggest that the privileged access of fearful faces
      to awareness does not occur mandatorily, but instead depends on attentional
      resources.

PMID- 20141311
TI  - The face in the crowd effect: anger superiority when using real faces and
      multiple identities.
AB  - The "face in the crowd effect" refers to the finding that threatening or angry
      faces are detected more efficiently among a crowd of distractor faces than happy
      or nonthreatening faces. Work establishing this effect has primarily utilized
      schematic stimuli and efforts to extend the effect to real faces have yielded
      inconsistent results. The failure to consistently translate the effect from
      schematic to human faces raises questions about its ecological validity. The
      present study assessed the face in the crowd effect using a visual search
      paradigm that placed veridical faces, verified to exemplify prototypical
      emotional expressions, within heterogeneous crowds. Results confirmed that angry
      faces were found more quickly and accurately than happy expressions in crowds of
      both neutral and emotional distractors. These results are the first to extend the
      face in the crowd effect beyond homogenous crowds to more ecologically valid
      conditions and thus provide compelling evidence for its legitimacy as a
      naturalistic phenomenon.

PMID- 20141313
TI  - Same-different discrimination: the keel and backbone of thought and reasoning.
AB  - Discriminating same from different collections of items is central to human
      thought and reasoning. Recent comparative research suggests that same-different
      discrimination behavior is not uniquely human, does not require human language,
      is based on the variability of the collection of items, obeys fundamental
      psychophysical laws, and may be captured by quantitative models of the stimulus
      collection. The comparative study of same-different discrimination behavior sheds
      fresh light on the mechanisms and functions of abstract conceptualization. This
      study also has prompted the development of a theory-the Finding Differences Model
      that successfully explains a wealth of findings in the comparative psychology of
      same-different discrimination behavior.

PMID- 20141315
TI  - Conditional same-different discrimination by pigeons: acquisition and
      generalization to novel and few-item displays.
AB  - The authors explored whether pigeons can learn to discriminate simultaneously
      presented arrays of 16 identical (Same) visual items from arrays of 16
      nonidentical (Different) visual items, when the correct choice was conditional on
      the presence of another cue: the color of the background. In one experiment,
      pigeons rapidly learned this task and, after training with arrays created from a
      72-icon set, they exhibited nearly perfect transfer to novel testing arrays. In a
      second experiment, pigeons' accuracy to 24-, 20-, 12-, and 8-icon arrays during
      later testing remained as high as accuracy to training arrays; although accuracy
      declined with 4- and 2-icon arrays, it was still significantly above chance. In
      both experiments, pigeons' choice reaction time scores nicely complemented their
      choice accuracy scores. These results suggest that the conditional discrimination
      procedure is well suited to disclose same-different discrimination in pigeons and
      to elucidate the interaction between perception and abstraction in conceptual
      learning.

PMID- 20141316
TI  - Stages of category learning in monkeys (Macaca mulatta) and humans (Homo
      sapiens).
AB  - Smith and Minda (1998) and Blair and Homa (2001) studied the time course of
      category learning in humans. They distinguished an early, abstraction-based stage
      of category learning from a later stage that incorporated a capacity for
      categorizing exceptional category members. The present authors asked whether
      similar processing stages characterize the category learning of nonhuman
      primates. Humans (Homo sapiens) and monkeys (Macaca mulatta) participated in
      category-learning tasks that extended Blair and Homa's paradigm comparatively.
      Early in learning, both species improved on typical items more than on exception
      items, indicating an initial mastery of the categories' general structure. Later
      in learning, both species selectively improved their exception-item performance,
      indicating exception-item resolution or exemplar memorization. An initial stage
      of abstraction-based category learning may characterize categorization across a
      substantial range of the order Primates. This default strategy may have an
      adaptive resonance with the family resemblance organization of many natural-kind
      categories.

PMID- 20141319
TI  - Effect of reward probability on spatial and temporal variation.
AB  - Gharib, Derby, and Roberts (2001) proposed that reducing reward expectation
      increases variation of response form. We tested this rule in a new situation and
      asked if it also applied to variation of response location and timing. In 2
      discrete-trial experiments, pigeons pecked colored circles for food. The circles
      were of 6 possible colors, each associated with a different probability of
      reward. Reducing reward expectation did not affect peck duration (a measure of
      form) but did increase horizontal variation of peck location and interpeck
      interval variation. The effect of reward probability on the standard deviation of
      interpeck intervals was clearer (larger t value) than its effect on mean
      interpeck interval. Two datasets from rats had similar interresponse-interval
      effects.

PMID- 20141317
TI  - Implicit and explicit category learning by macaques (Macaca mulatta) and humans
      (Homo sapiens).
AB  - An influential theoretical perspective differentiates in humans an explicit, rule
      based system of category learning from an implicit system that slowly associates
      different regions of perceptual space with different response outputs. This
      perspective was extended for the 1st time to the category learning of nonhuman
      primates. Humans (Homo sapiens) and macaques (Macaca mulatta) learned categories
      composed of sine-wave gratings that varied across trials in bar width and bar
      orientation. The categories had either a single-dimensional, rule-based solution
      or a two-dimensional, information-integration solution. Humans strongly
      dimensionalized the stimuli and learned the rule-based task far more quickly. Six
      macaques showed the same performance advantage in the rule-based task. In humans,
      rule-based category learning is linked to explicit cognition, consciousness, and
      declarative reports about the contents of cognition. These results demonstrate an
      empirical continuity between human and nonhuman primate cognition, suggesting
      that nonhuman primates may have some structural components of humans' capacity
      for explicit cognition.

PMID- 20141318
TI  - What do Arabic numerals mean to macaques (Macaca mulatta)?
AB  - In the past, rhesus macaques (Macaca mulatta) have demonstrated an ability to use
      Arabic numerals to facilitate performance in a variety of tasks. However, it
      remained unclear whether they understood the absolute and relative values of
      numerals. In Experiment 1, numeral-trained macaques picked the larger stimuli
      when presented with pairwise comparisons involving numerals and analog
      quantities. In Experiment 2, macaques were provided with numeral cues indicating
      the number of times a behavior could be performed in one location for a reward.
      Of the 4 monkeys, 3 performed above chance, but they often erred by performing
      more behaviors than indicated. The results of these studies indicate that the
      monkeys have knowledge of the approximate quantities represented by each numeral.

PMID- 20141320
TI  - Searching in the middle-Capuchins' (Cebus apella) and bonobos' (Pan paniscus)
      behavior during a spatial search task.
AB  - In this study we show that bonobos and capuchin monkeys can learn to search in
      the middle of a landmark configuration in a small-scale space. Five bonobos (Pan
      paniscus) and 2 capuchin monkeys (Cebus apella) were tested in a series of
      experiments with the expansion test paradigm. The primates were trained to search
      in the middle of a 4- or 2-landmark configuration, and were then tested with the
      same configuration expanded. Neither species searched in the middle of the
      expanded 4-landmark configuration. When presented with a 2-landmark configuration
      and a constant or variable inter-landmark training distance, the subjects
      sometimes searched preferentially in the middle of the expanded configuration. We
      discuss 2 alternative explanations of the results: extracting a middle rule or
      averaging between different goal-landmark vectors. In any case, compared to adult
      humans, primates appear highly constrained in their abilities to search in the
      middle of a configuration of detached landmarks. We discuss some of the factors
      that may influence the primates' behavior in this task.

PMID- 20141321
TI  - Rats' orientation is more important than start point location for successful
      place learning.
AB  - Rats were trained to locate food on a plus maze that was moved between 2
      locations. The food was in a fixed location relative to room cues but the maze,
      and the animals' start point, were either translated (shifted to the left or
      right) or rotated (by 90 degrees or 45 degrees ) across trials. Rats started from
      the same or different places solved the problem if they headed in a direction
      different from the start point. Rats started from different places were impaired
      if they headed in the same direction, suggesting that orientation is more
      important than start point for successful performance. The same pattern of
      results was obtained when rats were trained inside a curtained enclosure,
      suggesting that orientation is not derived solely from a view of distal visual
      cues while on the maze. It appears that rats use their heading, or direction of
      movement, to guide their responses at a choice point.

PMID- 20141322
TI  - Learned avoidance of flavors signaling reduction in a nutrient.
AB  - Food-deprived rats learned to avoid a flavor negatively correlated with access to
      a rich nutrient, 20% maltodextrin (20M) solution. This avoidance in two-bottle
      choice tests was produced by training consisting of either an unpaired condition
      where sessions of unflavored 20M were intermixed with sessions of 2 or 3%
      maltodextrin (2M or 3M) flavored with salt (Experiment 1) or almond (Experiments
      3 and 4) or a differential conditioning procedure where one flavor was mixed with
      20M and another with 2M (Experiment 2). Avoidance was counter-conditioned by
      mixing the target flavor with 20M (Experiment 1), generalized to a neutral
      context (Experiment 3), and displayed strong resistance to extinction (Experiment
      4). The results demonstrated that food avoidance learning can occur in the
      absence of an aversive unconditioned stimulus and indicated that unpaired control
      groups and differential conditioning procedures may be misleading in flavor
      preference learning research when further control conditions are absent.

PMID- 20141324
TI  - Contrasting predictions of extended comparator hypothesis and acquisition-focused
      models of learning concerning retrospective revaluation.
AB  - Three conditioned suppression experiments with rats investigated contrasting
      predictions made by the extended comparator hypothesis and acquisition-focused
      models of learning, specifically, modified SOP and the revised Rescorla-Wagner
      model, concerning retrospective revaluation. Two target cues (X and Y) were
      partially reinforced using a stimulus relative validity design (i.e., AX-Outcome;
      BX-No outcome; CY-Outcome; DY-No outcome), and subsequently one of the companion
      cues for each target was extinguished in compound (BC-No outcome). In Experiment
      1, which used spaced trials for relative validity training, greater suppression
      was observed to target cue Y for which the excitatory companion cue had been
      extinguished in relation to target cue X for which the nonexcitatory companion
      cue had been extinguished. Experiment 2 replicated these results in a sensory
      preconditioning preparation. Experiment 3 massed the trials during relative
      validity training, and the opposite pattern of data was observed. The results are
      consistent with the predictions of the extended comparator hypothesis.
      Furthermore, this set of experiments is unique in being able to differentiate
      between these models without invoking higher-order comparator processes.

PMID- 20141323
TI  - Using context to resolve temporal ambiguity.
AB  - Three conditioned lick suppression experiments with rats examined the role of the
      context in the selection and integration of independently acquired interval
      relationships. In Experiment 1, rats were exposed to separate conditioned stimuli
      1 and 2 (CS1-CS2) pairings with 2 different interval relationships, each in its
      own distinctive context, X or Y. The resultant integration was determined by the
      training context (X or Y) in which unconditioned stimulus (US)-CS2 backward
      pairings occurred, as assessed in a third neutral context (Z). In Experiment 2,
      rats experienced CS1-CS2 pairings with 2 different interval relationships as in
      Experiment 1, and then received US-CS2 pairings in both contexts X and Y. The
      testing context (i.e., X or Y) determined the resultant integration. In
      Experiment 3, rats were exposed to CS1-CS2 pairings in 2 different interval
      relationships each in different phases (i.e., Phases 1 and 2), and then in Phase
      3 received US-CS2 pairings. The temporal context of testing (i.e., short or long
      retention interval) determined the resultant integration. Thus, both physical and
      temporal context can be used to disambiguate conflicting temporal information.

PMID- 20141325
TI  - Contrasting the edge- and surface-based theories of object recognition:
      behavioral evidence from macaques (Macaca mulatta).
AB  - This study assessed the contribution of edge and surface cues on object
      representation in macaques (Macaca mulatta). In Experiments 1 and 2, 5 macaques
      were trained to discriminate 4 simple volumetric objects (geons) and were
      subsequently tested for their ability to recognize line drawings, silhouettes,
      and light changes of these geons. Performance was above chance in all test
      conditions and was similarly high for the line drawings and silhouettes of geons,
      suggesting the use of the outline shape to recognize the original objects. In
      addition, transfer for the geons seen under new lighting was greater than for the
      other stimuli, stressing the importance of the shading information. Experiment 3,
      using geons filled with new textures, showed that a radical change in the surface
      cues does not prevent object recognition. It is concluded that these findings
      support a surface-based theory of object recognition in macaques, although it
      does not exclude the contribution of edge cues, especially when surface details
      are not available.

PMID- 20141326
TI  - Contrasting object-based and texture-based accounts of same/different
      discrimination learning with trial-unique stimuli.
AB  - Same/different discrimination is a classic task for investigating relational
      learning in animals. Recent research suggests that pigeons can learn a trial
      unique same/different discrimination, which eliminates the opportunity to
      memorize the training items (Brooks & Wasserman, 2008). The authors conducted
      three tests to elucidate the role that item-based comparison plays in this trial
      unique discrimination. In the first, the authors tested the possibility that
      pigeons' same/different discrimination was based on textural features of the
      displays by creating a single, unitary texture from same and different displays;
      pigeons failed to discriminate these unitary textural displays. In the second,
      the authors varied the number of items (mosaics) in the display and the authors
      reproduced the characteristic decline in performance associated with fewer items.
      In the third, the authors systematically increased the area of two mosaics to
      closely match the area occupied by increasing numbers of mosaics; the results
      obtained with two small items persisted even when the size of the mosaics was
      increased. These results clearly show that pigeons' same/different discrimination
      was based on object-level variability and not on other properties of the
      displays.

PMID- 20141327
TI  - Occurrence of the Vibrio cholerae seventh pandemic VSP-I island and a new
      variant.
AB  - Using comparative genomics, we identified a new variant of the Vibrio Seventh
      Pandemic Island-I (VSP-I). Results of polymerase chain reaction (PCR) screening
      for both known VSP-I variants indicate that the novel variant is present only in
      non-O1/non-O139 strains of V. cholerae and Vibrio mimicus. Comparative genomics
      revealed little sequence divergence in the seventh pandemic VSP-I; however, a
      second insertion site located on the smaller chromosome was identified. Although
      the seventh pandemic VSP-I genomic island was detected in all seventh pandemic V.
      cholerae serogroup O1 and O139 isolates examined in this study, unique genes of
      the island cannot be used alone as an identifying target, because the seventh
      pandemic VSP-I was also present in three non-seventh pandemic strains of V.
      cholerae isolated from Chesapeake Bay. As an alternative, a PCR assay targeting
      the VC2346 gene was found to be confirmatory for seventh pandemic isolates of V.
      cholerae.

PMID- 20141329
TI  - Albumin overload induces apoptosis in renal tubular epithelial cells through a
      CHOP-dependent pathway.
AB  - The proteinuria-induced apoptosis of proximal tubular cells (PTCs) plays a
      crucial role in renal tubulointerstitial injury in chronic kidney disease. Recent
      studies have shown that endoplasmic reticulum (ER) stress is involved in
      proteinuria-induced apoptosis of PTCs. Our study showed that albumin overload led
      to ER stress, CCAAT/enhancer-binding protein-homologous protein (CHOP), and PKR
      like kinase (PERK) activation and to apoptosis of PTCs in proteinuria patients.
      The apoptotic index of proximal renal tubular cells in the nephrotic kidneys was
      about 13-fold higher than that in control kidneys. The increased tubular
      expression of GRP78, ORP150, and CHOP and nuclear localization of CHOP in
      nephrotic kidneys were also detected. The expression of GRP78, CHOP, PERK, and
      phosphorylated PERK increased proportionately with HSA overload in a dose- and
      time-dependent manner. Knockdown of CHOP by siRNA significantly reduced the HSA
      induced apoptosis of HKC. The expression of PERK did not significantly change,
      but the phosphorylation of PERK increased. Furthermore, knockdown of PERK
      significantly inhibited HSA-induced CHOP expression, suppressing apoptosis in
      HKCs by 2.48-fold compared to controls. Overexpression of CHOP enhanced the
      apoptosis of HKC induced by albumin, no significant difference was observed in
      the expression of PERK, whereas the phosphorylation of PERK decreased. Our data
      indicated that proteinuria induces ER stress in renal tubular cells, which may
      subsequently lead to tubular damage through a PERK-CHOP-dependent pathway. This
      ER stress-induced apoptosis pathway may contribute to renal tubulointerstitial
      injury by proteinuria in chronic kidney disease.

PMID- 20141328
TI  - A persistent and diverse airway microbiota present during chronic obstructive
      pulmonary disease exacerbations.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major
      source of morbidity and contribute significantly to healthcare costs. Although
      bacterial infections are implicated in nearly 50% of exacerbations, only a
      handful of pathogens have been consistently identified in COPD airways, primarily
      by culture-based methods, and the bacterial microbiota in acute exacerbations
      remains largely uncharacterized. The aim of this study was to comprehensively
      profile airway bacterial communities using a culture-independent microarray, the
      16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support
      and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip
      analysis revealed the presence of over 1,200 bacterial taxa representing 140
      distinct families, many previously undetected in airway diseases; bacterial
      community composition was strongly influenced by the duration of intubation. A
      core community of 75 taxa was detected in all patients, many of which are known
      pathogens. Bacterial community diversity in COPD airways is substantially greater
      than previously recognized and includes a number of potential pathogens detected
      in the setting of antibiotic exposure. Comprehensive assessment of the COPD
      airway microbiota using high-throughput, culture-independent methods may prove
      key to understanding the relationships between airway bacterial colonization,
      acute exacerbation, and clinical outcomes in this and other chronic inflammatory
      airway diseases.

PMID- 20141330
TI  - Ginkgo biloba extract induces gene expression changes in xenobiotics metabolism
      and the Myc-centered network.
AB  - The use of herbal dietary supplements in the United States is rapidly growing,
      and it is crucial that the quality and safety of these preparations be ensured.
      To date, it is still a challenge to determine the mechanisms of toxicity induced
      by mixtures containing many chemical components, such as herbal dietary
      supplements. We previously proposed that analyses of the gene expression profiles
      using microarrays in the livers of rodents treated with herbal dietary
      supplements is a potentially practical approach for understanding the mechanism
      of toxicity. In this study, we utilized microarrays to analyze gene expression
      changes in the livers of male B6C3F1 mice administered Ginkgo biloba leaf extract
      (GBE) by gavage for 2 years, and to determine pathways and mechanisms associated
      with GBE treatments. Analysis of 31,802 genes revealed that there were 129, 289,
      and 2,011 genes significantly changed in the 200, 600, and 2,000 mg/kg treatment
      groups, respectively, when compared with control animals. Drug metabolizing genes
      were significantly altered in response to GBE treatments. Pathway and network
      analyses were applied to investigate the gene relationships, functional
      clustering, and mechanisms involved in GBE exposure. These analyses indicate
      alteration in the expression of genes coding for drug metabolizing enzymes, the
      NRF2-mediated oxidative stress response pathway, and the Myc gene-centered
      network named "cell cycle, cellular movement, and cancer" were found. These
      results indicate that Ginkgo biloba-related drug metabolizing enzymes may cause
      herb-drug interactions and contribute to hepatotoxicity. In addition, the
      outcomes of pathway and network analysis may be used to elucidate the toxic
      mechanisms of Ginkgo biloba.

PMID- 20141331
TI  - A survey of cancer cell lines reveals highly structured and hierarchical
      relationships within and between DNA and mRNA that may be the result of
      selection.
AB  - Copy number variation (CNV) is one of the most profound forms of somatic DNA
      changes that underlie most human cancers. However, the degree of complexity
      within and between DNA and mRNA variations in cancer cohorts has yet to be fully
      characterized. Here we characterized the connectivity of CNV/CNV and its
      contribution to transcriptome in human cancer cell lines. Strikingly, we found
      there is a significant nonrandom correlation of many unlinked DNA loci and also a
      significant association between CNV and mRNA expression in cis and in trans
      (called eCNV). Both distributions of DNA/DNA and DNA/mRNA associations exhibit a
      scale-free structure showing that, for DNA/DNA, a few loci correlate to many
      other loci, whereas most loci correlate to only a few loci; and for DNA/mRNA,
      certain chromosomal loci associate with many mRNAs and that many mRNAs are
      controlled by more than one locus. This suggests that a small number of DNA loci
      act as hubs in a hierarchical structure that is highly nonrandom in nature, and
      genes linking to these hot spots tend to be involved in similar biological
      functions. Derivation of highly connected structures suggests a process of
      undirected copy number changes followed by selection of those advantageous to
      tumor cells during tumorigenesis. Given that the cohort includes many tissue
      types, our observations may identify a common and important underlying structure
      present in human tumors.

PMID- 20141332
TI  - Preliminary exploration of time course DNA microarray data with correlation maps.
AB  - In the analysis of data from high-throughput experiments, information regarding
      the underlying data structure provides the researcher with confidence in the
      appropriateness of various analysis methods. One extremely simple but powerful
      data visualization method is the correlation heat map, whereby correlations
      between experiments/conditions are calculated and represented using color. In
      this work, the use of correlation maps to shed light on transcription patterns
      from DNA microarray time course data prior to gene-level analysis is described.
      Using three different time course studies from the literature, it is shown how
      the patterns observed at the array level provide insights into the dynamics of
      the system under study and the experimental design.

PMID- 20141333
TI  - ConsensusCluster: a software tool for unsupervised cluster discovery in numerical
      data.
AB  - We have created a stand-alone software tool, ConsensusCluster, for the analysis
      of high-dimensional single nucleotide polymorphism (SNP) and gene expression
      microarray data. Our software implements the consensus clustering algorithm and
      principal component analysis to stratify the data into a given number of robust
      clusters. The robustness is achieved by combining clustering results from data
      and sample resampling as well as by averaging over various algorithms and
      parameter settings to achieve accurate, stable clustering results. We have
      implemented several different clustering algorithms in the software, including K
      Means, Partition Around Medoids, Self-Organizing Map, and Hierarchical clustering
      methods. After clustering the data, ConsensusCluster generates a consensus matrix
      heatmap to give a useful visual representation of cluster membership, and
      automatically generates a log of selected features that distinguish each pair of
      clusters. ConsensusCluster gives more robust and more reliable clusters than
      common software packages and, therefore, is a powerful unsupervised learning tool
      that finds hidden patterns in data that might shed light on its biological
      interpretation. This software is free and available from
      http://code.google.com/p/consensus-cluster .

PMID- 20141334
TI  - Comparison of normalization methods for the identification of biomarkers using
      MALDI-TOF and SELDI-TOF mass spectra.
AB  - Proteomic profiling by mass spectrometry has tremendous potential for identifying
      disease biomarkers. A key limitation of mass spectrometry is that the information
      provided on the abundance of the various peptides is only relative. Thus,
      normalization is typically employed. Several normalization methods have been
      proposed and implemented in the literature. However, it is not clear if there is
      any reason to prefer one method over another. The goal of this study was to
      investigate the effect of normalization strategy on the identification of
      putative biomarkers from MALDI-TOF and SELDI-TOF mass spectra. Our results
      demonstrate that many of the putative biomarkers identified by mass spectrometry
      will be the same regardless of which data normalization scheme is applied.
      However, there can be substantial differences in the m/z values identified as
      being most discriminatory based on choice of normalization method. As there is no
      consistent pattern as to which normalization method yields the most promising
      targets for follow up study, we recommend that investigators routinely repeat
      their analysis with multiple normalization methods and consider the top several
      candidates identified in each case.

PMID- 20141336
TI  - Gonadotrophin ovulation induction is a successful treatment for World Health
      Organisation Group II anovulatory subfertility in women aged up to 40 and with
      body mass index up to 34.
AB  - Gonadotrophin-induced ovulation (GnOI) is generally an effective treatment when
      anti-estrogen therapy is unsuccessful. It remains uncertain how appropriate it is
      in older and obese women. We carried out an analysis of a GnOI programme between
      2000 and 2008, including 514 treatment cycles in 140 women with World Health
      Organisation Group II anovulation. A low-dose step-up stimulation protocol using
      recombinant follicle stimulating hormone (FSH) (with natural intercourse) was
      used throughout in the treatment of women aged up to 40 years and with body mass
      index (BMI) up to 34 kg/m(2), with a rigorously-applied cancellation criterion.
      The livebirth rates in first stimulated cycle and cumulatively over six cycles
      (or until pregnancy) were 19.2% and 74.2%, respectively and the multiple
      livebirth rate was 2.5%. There was no significant relationship between age and
      BMI with pregnancy rates, although higher BMI was associated with higher
      threshold dose and longer duration of stimulation. Anti-estrogen resistant
      patients attained significantly higher cumulative ongoing pregnancy rates than
      those who were anti-estrogen responsive. These data demonstrate that judicious
      administration of gonadotrophins to women with WHO Group II anovulatory
      subfertility can result in a good pregnancy rate with low risk of multiple
      pregnancy in women aged up to 40 years and with BMI of up to 34 kg/m(2).

PMID- 20141337
TI  - Attitudes towards single embryo transfer, twin and higher order pregnancies in
      patients undergoing infertility treatment: a review.
AB  - The problems associated with twin and higher order pregnancies have assumed major
      importance, with international debate about multiple pregnancy; the single
      biggest risk with in vitro fertilisation (IVF). We have critically reviewed
      published papers on female patients' and their partners' views of single embryo
      transfer (SET) and twin or higher level pregnancies to identify the requirements
      needed to improve the acceptability of SET. Twenty relevant papers were
      identified and included in the review. Although the majority of IVF patients and
      their partners, in the more recent studies, exhibited a desire for twins rather
      than singletons, closer examination of the evidence revealed that elective SET
      (eSET) could become increasingly acceptable. As success rates of IVF have
      improved and the risks and consequences of multiple pregnancies are well
      documented, patients have accepted the transfer of two rather than three embryos
      as standard practice. However, more would accept eSET if success rates approached
      those of double embryo transfer (DET). This emphasises the importance of
      improving success rates of eSET so that more patients can achieve a singleton
      birth with one IVF cycle. If patients were offered only SET, it is likely that
      this would be acceptable as the normal expectation of pregnancy is one baby.
      Measures to improve the acceptability of SET include: using eSET, especially with
      younger patients; including partners when providing risk information; improving
      eSET success rates; improving outcomes with cryopreserved embryos; changing
      reimbursement/free cycles to favour eSET; using legal enforcement.

PMID- 20141338
TI  - Animal serum-free expansion and differentiation of human mesenchymal stromal
      cells.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) are attracting increasing
      interest for possible application in cell therapies. Fetal calf serum (FCS) is
      widely utilized for cell culture, but its use in the context of clinical
      applications is associated with too many risks. Therefore we tested FCS-free
      media for the expansion and differentiation of MSC in compliance with the
      European good manufacturing practice (GMP) regulations for medicinal products.
      METHODS: MSC expansion medium was modified by replacing FCS with human plasma and
      platelet extract. Cells were characterized according to the defined minimal
      criteria for multipotent MSC. For chondrogenic differentiation, serum-free
      micromass cultures were employed. For adipogenic and osteogenic differentiation,
      the FCS was replaced by human plasma. After 28 days of incubation in
      differentiation media, cells were analyzed by cytochemical and
      immunohistochemical staining. Furthermore, mRNA expression of chondrogenic,
      adipogenic and osteogenic markers was investigated by quantitative reverse
      transcription polymerase chain reaction (qRT-PCR). RESULTS: Expansion and
      differentiation of MSC under FCS-free conditions yielded cells with chondrogenic,
      adipogenic and osteogenic phenotypes and a characteristic gene expression.
      Chondrocytes in micromass pellets revealed an accumulation of proteoglycans and
      type II collagen as well as a significantly increased mRNA expression of
      chondrogenic marker genes. The adipocytes displayed Oil red O staining and
      expressed peroxisome proliferator-activated receptor gamma(2) (ppARgamma2) and
      lipoprotein lipase (LPL) mRNA. The osteoblasts were positive for von Kossa
      staining and expressed mRNA of osteogenic marker genes. The results did not
      indicate any spontaneous differentiation. CONCLUSIONS: Human plasma is a suitable
      FCS replacement for the expansion and differentiation of MSC, providing a
      feasible alternative for tissue engineering with GMP-compatible protocols.

PMID- 20141339
TI  - Expansion of human bone marrow-derived mesenchymal stromal cells: serum-reduced
      medium is better than conventional medium.
AB  - BACKGROUND AIMS: Human mesenchymal stromal cells (hMSC) are of enormous interest
      for various clinical applications. For the expansion of isolated hMSC to relevant
      numbers for clinical applications, 10% fetal bovine serum (FBS)-supplemented
      medium is commonly used. The main critical disadvantage of FBS is the possibility
      of transmission of infectious agents as well as the possibility of immune
      rejection of the transplanted cells in response to the bovine serum. Therefore,
      we tested a commercially available medium, Panserin 401, that was specifically
      developed for serum-free cell cultivation. METHODS: hMSC were isolated from bone
      marrow (BM) and expanded in either Dulbecco's modified Eagle medium (DMEM) or
      Panserin 401 alone, or combined with FBS (2% or 10%), with or without
      supplementary growth factors. Cell proliferation and cytotoxicity were monitored
      twice a week for 3 weeks. RESULTS AND CONCLUSIONS: No proliferation was observed
      in any of the serum-free media. However, DMEM/10% FBS (the conventional culture
      medium for hMSC) and DMEM/2% FBS with growth factors revealed moderate
      proliferation. Interestingly, the best proliferation was obtained using Panserin
      401 supplemented with 2% FBS and growth factors (as well as with 10% FBS).
      Analysis of cell growth in Panserin 401 supplemented with 2% FBS only or with
      growth factors only revealed no proliferation, demonstrating the necessity of the
      combination of 2% FBS and growth factors. Efficient isolation and expansion of
      hMSC from cancellous bone could also be performed using Panserin 401 with 2% FBS
      and growth factors. Furthermore, these isolated cultures maintained multipotency,
      as demonstrated by adipogenic and osteogenic differentiation.

PMID- 20141340
TI  - Intraoperative blood salvage and retransfusion from citrate treated wounds is
      safe and feasible.
AB  - OBJECTIVES: Allogenic blood transfusions are associated with increased morbidity
      and mortality in surgical patients. The study objective was to investigate the
      feasibility and safety of intraoperative autotransfusion of unwashed shed whole
      blood using a novel method. DESIGN: Twenty pigs were randomised to
      autotransfusion or crystalloid volume replacement. In two separate surgical
      wounds, the surfaces and 400 ml of shed blood were treated in situ with citrate,
      delivered with an equipment transforming suction to positive pressure. Central
      haemodynamics were monitored with a pulmonary artery catheter. Effects on oxygen
      carrying capacity, formed blood elements, haemolysis, inflammation, metabolism,
      and coagulation were evaluated with biochemical analyses. RESULTS: No clinically
      relevant adverse effects on haemodynamics were encountered, apart from a decrease
      in cardiac output and mixed venous saturation similar to that in control animals.
      Haemoglobin level was better preserved in the autotransfused group (97 vs. 86
      g/L, p=0.0007). There were no major differences in biochemical variables and no
      macroscopic clot formation precluding autotransfusion. CONCLUSIONS: The technique
      was safe and feasible for intraoperative blood salvage and autotransfusion.
      Haemodynamics and biochemical variables were similar to controls. The technique
      warrants further studies in humans, as it may contribute towards a reduction of
      allogenic blood transfusions.

PMID- 20141341
TI  - Inflammatory/oxidative stress during the first week after different types of
      cardiac surgery.
AB  - OBJECTIVES: To compare inflammatory and oxidative stress time course during the
      first week after different types of cardiac surgery. DESIGN: In patients
      undergoing coronary artery bypass grafting with cardiopulmonary bypass (CABG) or
      on the working heart (OPCAB) and aortic valve replacement (VALVE) blood samples
      for high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6),
      myeloperoxidase (MPO), asymmetric dimethylarginine (ADMA) and homocysteine (Hcy)
      were taken preoperatively and for six consecutive postoperative days. RESULTS:
      Exploitation of cardiopulmonary bypass (CABG, VALVE groups), but not OPCAB,
      resulted in significant rise of MPO for two postoperative days. ADMA and Hcy
      changed in parallel fashion, being significantly decreased in the first
      postoperative morning and rising to the preoperative levels thereafter. In
      comparison with coronary artery disease patients, VALVE group had lower
      preoperative levels of ADMA and different postoperative time course.
      Postoperative concentrations of IL-6 and hsCRP were increased significantly in
      all groups and remained elevated during the first postoperative week.
      CONCLUSIONS: Cardiac surgery results in extensive and complex
      inflammatory/oxidative stress response regardless of the method or type of
      surgical procedure used. Myeloperoxidase could be one of the parameters to
      evaluate the cardiopulmonary bypass-associated inflammatory and oxidative stress
      response.

PMID- 20141342
TI  - Tattooing in the Gulf region: a review of tattoo practices and response to
      treatment with the Q-switched ruby laser.
AB  - BACKGROUND: Data regarding tattoo practices in the Gulf region and response to
      treatment are almost non-existent in the medical literature. OBJECTIVE: To study
      the profile of patients with permanent tattoos in the Arab world, and to evaluate
      their response to Q-switched ruby laser treatment. METHODS: A total of 468
      consecutive patients with permanent tattoos consulting us for tattoo removal were
      recruited in the present study. Before starting the treatment each patient was
      given a set of questionnaires to answer. The patients were then treated with the
      Q-switched ruby laser, with a time interval of 8 weeks between each laser
      session, until complete clearance or up to a maximum of 10 sessions. RESULTS: A
      total of 292 patients out of 348 patients achieved excellent lightening to
      complete clearance of tattoo pigment after an average of six sittings (range 2-10
      sittings). Female patients with fair complexions and amateur tattoos on the face
      responded best. Seventy-eight (22.4%) patients developed pigmentary changes.
      CONCLUSION: More females than males had tattoos, and at a very young age and
      mostly on the advice of their parents. The majority of patients wanted to remove
      the tattoos because of religious reasons. The Q-switched ruby laser seems to be
      highly effective in removing amateur blue-black tattoos in patients with colored
      skin.

PMID- 20141343
TI  - Metabolic therapy in cardiac surgery--"Optimizing the engine's fuel supply and
      more...".

PMID- 20141344
TI  - A metabolic protective strategy could improve long-term survival in patients with
      LV-dysfunction undergoing CABG.
AB  - OBJECTIVE: Adverse outcome after CABG is closely related to postoperative heart
      failure precipitated by ischemia and myocardial infarction. Restrictive use of
      inotropes is therefore desirable. Patients with preoperative left ventricular
      dysfunction are a high-risk group in this respect. To reduce myocardial oxygen
      expenditure we evolved a metabolic strategy for perioperative care. DESIGN:
      Observational study on 104 consecutive patients with severe left ventricular
      dysfunction undergoing CABG. The metabolic strategy implied physiological
      measures to minimize myocardial oxygen expenditure including restrictive use of
      inotropes and specific measures such as extended CPB and metabolic support to
      facilitate myocardial recovery. Hemodynamic state was primarily assessed by mixed
      venous oxygen saturation (SvO(2)). Follow-up averaged 9.7+/-1.4 years. RESULTS:
      LVEF was 0.30+/-0.05 (range 0.20-0.37) and 3.5+/-1.3 vessels were bypassed.
      Inotropes were used in 6.7% for weaning from CPB. Increase of s-creatinine by >
      or =50% compared to preoperative values was observed in 2.9%. Logistic EuroSCORE
      was 8.3% whereas observed 30-day mortality was 1.0%. Crude 5-year survival was
      89.4%. CONCLUSIONS: The metabolic strategy allowed restrictive use of inotropes
      and was associated with encouraging long-term survival. Renal function was well
      preserved suggesting that SvO(2) served as an adequate marker of circulation.
      Randomized trials with metabolic support are warranted.

PMID- 20141345
TI  - Survival characteristics of Cronobacter spp. in model bovine gut and in the
      environment.
AB  - Cronobacter spp. (formally Enterobacter sakazakii) have been linked to illness in
      infants from contaminated powdered infant formula. The source of the pathogen
      remains unclear, and it is believed that farm environments and cattle could play
      a role in the transmission of Cronobacter spp. The aim of this study was to
      establish if the organism would survive passage through a model of the bovine
      rumen and abomasum and in bovine feces in the farm environment. Models of the
      bovine abomasum and rumen were inoculated with Cronobacter strains (final
      concentrations of 5.7 and 6.5 log(10) CFU/mL, respectively), and survival was
      examined over time in these environments using an adapted ISO/DTS 22964 culture
      protocol. Fecal samples were inoculated with Cronobacter (final concentration 6.0
      log(10) CFU/mL), and survival on soil and in containers stored outdoors was
      examined over time. The results showed no significant changes in the number of
      Cronobacter in rumen fluid over a 24-h period. Cronobacter were undetectable
      after 30 min of incubation in the model abomasum. The pathogen survived 105 days
      in sealed containers and was detectable after 112 days in soil. This study
      indicated that Cronobacter spp. are unlikely to be shed in bovine feces as
      supported by previous surveillance studies; however, the study did show that the
      organism survives well in the farm environment.

PMID- 20141346
TI  - Microbiological quality of milk from small processing units in Senegal.
AB  - Consumption of milk and dairy products has increased significantly in Senegal in
      the last decade, and a large part of the local production comes from small
      processing units spread all over the country. We collected 85 bulk-tank milk
      samples from 68 smallholder dairy farms throughout the territory. Microbiological
      quality of milk samples was analyzed according to the official standards.
      Further, raw milk and pasteurized milk were screened for Mycobacterium bovis,
      Coxiella burnetii, and anti-Brucella abortus antibodies. Ninety-three percent of
      pasteurized milk samples, 92% of raw milk samples, and 81% of sour milk samples
      failed to meet official standards. Pathogens detected in milk were C. burnetii
      (6/41, 15%), which seems to be endemic in Senegal, coagulase-positive
      staphylococci (18/70, 26%), and Salmonella Johannesburg in one sample. Further
      analysis of coagulase-positive staphylococci isolated from samples containing
      more than 10(4) colony-forming units per gram showed the presence of
      enterotoxigenic strains in 9 of the 10 samples. These results confirm the poor
      microbiological quality of milk produced by small units in Senegal, especially
      and surprisingly of pasteurized milk. This highlights the need to implement good
      hygiene practices, particularly in the postpasteurization process, and an
      effective monitoring throughout the production and delivery chain.

PMID- 20141347
TI  - Chicken meat is an infection source of Salmonella serovar Infantis for humans in
      Japan.
AB  - BACKGROUND: The study sets out to either confirm or refute a recent study's
      findings that chicken meat is an unlikely source of Salmonella enterica
      subspecies enterica serovar Infantis (Salmonella Infantis) in humans in the
      Kyushu-Okinawa region, Japan. METHODS: A total of 74 Salmonella Infantis isolates
      (30 from human and 44 from other sources), mainly from the Kyushu-Okinawa region
      in south-western Japan, were analyzed using a molecular-epidemiological approach
      combining two fingerprinting methods, namely pulsed-field gel electrophoresis and
      amplified fragment length polymorphism (AFLP), a novel polymerase chain reaction
      based technique. RESULTS: The resulting pulsed-field profiles showed that 17 of
      30 human isolates were similar to those found in chicken meat, whereas there were
      no common pulsed-field profiles between human and chicken egg isolates. Overall,
      3 of 18 AFLP profiles included 7 human isolates and 14 chicken egg isolates. In
      addition, the combined results of the pulsed-field gel electrophoresis and AFLP
      analyses showed that 8 human Salmonella Infantis and 13 chicken meat isolates
      belonged to the same clonal lines. CONCLUSIONS: These results suggest that
      chicken meat is an infection source of Salmonella Infantis for humans in the
      Kyushu-Okinawa region, Japan. The results also showed the relatively high
      suitability of AFLP for application to epidemiological studies of Salmonella
      Infantis.

PMID- 20141348
TI  - A new paradigm for managing dyslipidemia with combination therapy: laropiprant +
      niacin + simvastatin.
AB  - IMPORTANCE OF THE FIELD: Despite effective lowering of low-density lipoprotein
      cholesterol (LDL-C) with statin for prevention of cardiovascular adverse events,
      residual risk remains high due to low high-density lipoprotein cholesterol (HDL
      C) levels in patients with mixed dyslipidemia. As a result, alternative treatment
      options to raise HDL-C are being investigated intensively. Currently, niacin is
      the most potent lipid lowering agent for raising HDL-C levels together with
      lowering of triglyceride and LDL-C. Previous clinical studies have demonstrated
      that niacin therapy significantly reduces the risk of cardiovascular events in
      high risk subjects. However, the clinical use of niacin is limited by its major
      adverse effect, cutaneous flushing. Although the use of extended-release (ER)
      formulation can reduce flushing, the tolerability and compliance of niacin
      remains suboptimal. A selective antagonist of prostaglandin D Type 1 receptor,
      laropiprant, has been investigated in a number of clinical studies and shown to
      be effective in reducing niacin-induced flushing. Despite the potential of
      laropiprant in reducing niacin-induced flushing, the long-term clinical efficacy
      and potential off-target side effects are not well studied. AREAS COVERED IN THIS
      REVIEWS: In this article, the pharmacological properties, clinical efficacy and
      future perspective of this combination therapy of simvastatin/ER
      niacin/laropiprant are reviewed. WHAT THE READER WILL GAIN: Readers will
      understand both the mechanism and clinical effects of the combination therapy of
      simvastatin/ER niacin/laropiprant. TAKE HOME MESSAGE: The triple combination
      therapy of simvastatin/ER niacin/laropiprant may reduce flushing side effects and
      facilitate a more comprehensive treatment for patients with mixed dyslipidemia.

PMID- 20141349
TI  - Lestaurtinib, a multitargeted tyrosine kinase inhibitor: from bench to bedside.
AB  - IMPORTANCE OF THE FIELD: Internal tandem duplication of the fms-like tyrosine
      kinase 3 (FLT3) gene (FLT3-ITD) is a common recurring mutation in acute myeloid
      leukemia (AML) with normal karyotype, and the presence of FLT3-ITD confers a poor
      prognosis on this large subgroup of AML patients. Since the discovery of
      lestaurtinib as a potent FLT3 inhibitor, in 1985, there has been considerable
      interest in the development of this agent (CEP-701, Cephalon, Frazer, PA, USA)
      for treatment of this population. AREAS COVERED IN THIS REVIEW: An extensive
      literature search was conducted that included published articles and abstracts on
      the preclinical and clinical development of this agent spanning the last decade.
      WHAT THE READER WILL GAIN: The review describes the historical development of
      this agent and reviews the available preclinical and clinical data on
      lestaurtinib and expands on potential future directions in development of this
      agent. TAKE HOME MESSAGE: Lestaurtinib is a multi targeted tyrosine kinase
      inhibitor which has been shown to potently inhibit FLT3 at nanomolar
      concentrations in preclinical studies, leading to its rapid development as a
      potential targeted agent for treatment of AML. Phase I studies have shown
      lestaturtinib to be an active agent particularly when used in combination with
      cytotoxic drugs. Currently, Phase II and Phase III studies are underway aiming to
      establish the future of this agent as a treatment option for patients with FLT3
      ITD AML.

PMID- 20141350
TI  - New microtubule-inhibiting anticancer agents.
AB  - IMPORTANCE OF THIS FIELD: Microtubule-inhibiting drugs are among the most
      commonly prescribed agents in the combat against cancer, though the clinical use
      of these drugs is limited by acquired resistance, risk of hypersensitivity
      reactions and intolerable toxicity. With progress in our understanding of
      cytoskeleton structure and its related signaling pathways, a number of new
      microtubule-inhibiting agents with diversified structures and modes of action
      have emerged. WHAT THE READER WILL GAIN: This review mainly describes new
      microtubule-targeting anticancer agents that have been discovered (especially
      over the past 2 years), with emphasis on their diversity of structures and
      distinct modes of action. AREAS COVERED IN THIS REVIEW: Data were obtained
      exclusively from public sources, including journals and scientific meeting
      abstracts, up to September 2009. TAKE HOME MESSAGE: A number of new agents have
      been discovered, and some have entered clinical trials. Even though most of these
      agents stabilize or destabilize tubulin via binding on the recognized tubulin
      binding sites, a few compounds bind to tubulin on undefined sites or interrupt
      microtubule in diverse ways. Moreover, some agents target microtubule indirectly
      such that they alter the post-translational modification of tubulin. Further
      investigation into their mechanism of action and evaluation of their anticancer
      efficacy will help to develop novel regimens that are superior to existing
      approaches.

PMID- 20141352
TI  - Ophthalmologic abnormalities in a de novo terminal 6q deletion.
AB  - PURPOSE: To correlate the clinical phenotype with the genotype of a boy with a
      terminal deletion of chromosome 6q and to compare these observations to previous
      reports of 6q deletions and review of the literature. METHODS: Careful clinical
      evaluation, conventional cytogenetic analysis on GTG-banded chromosomes and 244K
      array CGH analysis. RESULTS: This 14 year old Saudi boy had modest mental
      retardation, seizures, microcephaly, cortical dysplasia, a non-comitant
      esotropia, impersistent eccentric gaze, congenital nystagmus, thick corneas, and
      substantial myopia. He had a de novo 10.79 Mb deletion on chromosome 6 from
      6q25.3 to 6qter. The deleted region extended from nucleotide 159929512 to
      170723629 and encompassed 87 genes. Eleven genes remained within the proband's
      deleted region after excluding genes located in deleted areas reported in
      phenotypically normal individuals. Among those 11 genes, only the TBP (TATA box
      binding protein) gene has been associated with any symptom or sign observed in
      our patient. CONCLUSIONS: This boy had clinical features similar to patients
      reported with the 6q terminal deletion syndrome. In addition, he had an unusual
      ocular motility pattern and thick corneas, features that may be more common than
      previously recognized. Deleted genes in this area of chromosome 6 may contribute
      to ophthalmic abnormalities in addition to mental retardation.

PMID- 20141351
TI  - Novel targets for the treatment of autosomal dominant polycystic kidney disease.
AB  - IMPORTANCE OF THE FIELD: Autosomal dominant (AD) polycystic kidney disease (PKD)
      is the most common life-threatening hereditary disorder. There is currently no
      therapy that slows or prevents cyst formation and kidney enlargement in humans.
      An increasing number of animal studies have advanced our understanding of
      molecular and cellular targets of PKD. AREAS COVERED IN THE REVIEW: The purpose
      of this review is to summarize the molecular and cellular targets involved in
      cystogenesis and to update on the promising therapies that are being developed
      and tested based on knowledge of these molecular and cellular targets. WHAT THE
      READER WILL GAIN: Insight into the pathogenesis of PKD and how a better
      understanding of the pathogenesis of PKD has led to the development of potential
      therapies to inhibit cyst formation and/or growth and improve kidney function.
      TAKE HOME MESSAGE: The results of animal studies in PKD have led to the
      development of clinical trials testing potential new therapies to reduce cyst
      formation and/or growth. A vasopressin V2 receptor antagonist, mTOR inhibitors,
      blockade of the renin-angiotensin system and statins that reduce cyst formation
      and improve renal function in animal models of PKD are being tested in
      interventional studies in humans.

PMID- 20141353
TI  - Spondylometaphyseal dysplasia with cone-rod dystrophy.
AB  - PURPOSE: To report on the clinical ophthalmologic and radiographic findings in
      spondylometaphyseal dysplasia with cone-rod dystrophy. BACKGROUND: The
      spondylometaphyseal dysplasias are a rare and heterogeneous group of disorders
      characterized by skeletal abnormalities of the spine and the metaphyses of long
      bones. In rare instances, spondylometaphyseal dysplasia can occur concomitantly
      with ocular abnormalities including a retinal degeneration of the cone-rod
      dystrophy type. METHODS: Retrospective review of affected twin females with
      serial radiographic imaging, comprehensive ophthalmologic examination, fundus
      photography, and electroretinography. RESULTS: The major radiographic findings
      involved bony abnormalities of the spine, metaphyses of the long bones and a
      distinctive shape to the bony pelvis. Both twins had a fine nystagmus that was
      present by 10 months of age. Dilated ocular fundus examination revealed similar
      appearing bilateral, large, excavated, well-circumscribed oval areas of
      chorioretinal atrophy occupying the macula between the aracades.
      Electroretinography showed a significant reduction in the photopic responses and
      slight reduction in the scotopic component of the waveforms consistent with cone
      rod dystrophy. CONCLUSIONS: Spondylometaphyseal dysplasia with cone-rod dystrophy
      is a rare congenital disorder of unknown inheritance pattern and pathophysiolgy.
      The ocular manifestations appear to stabilize in early adolescence whereas the
      skeletal abnormalities are progressive with age.

PMID- 20141354
TI  - Protein kinase C beta (PRKCB1) and pigment epithelium derived factor (PEDF) gene
      polymorphisms and diabetic retinopathy in a south Indian cohort.
AB  - PURPOSE: Polymorphisms in protein kinase C beta (PRKCB1) and pigment epithelium
      derived factor (PEDF) genes have been associated with diabetic nephropathy and
      retinopathy respectively. Association of promoter polymorphisms-1504C/T and
      1440G/T in PRKCB1 gene and sequence variations in exon 4 of PEDF gene are studied
      with diabetic retinopathy (DR) in a south Indian population based cohort.
      METHODS: Type 2 diabetic patients with and without retinopathy (DR+ and DR-
      respectively) were recruited. The promoter region of PRKCB1 gene and exon 4 of
      PEDF genes were sequenced by polymerase chain reaction based direct sequencing
      and their frequencies were analyzed using relevant statistical tests. RESULTS:
      The genotype and alleles of the two promoter polymorphisms of PRKCB1 gene were
      uniformly distributed among DR+ and DR- and hence were not associated with the
      disease. The haplotypes were also not significantly associated with DR. A T130T
      polymorphism observed in the PEDF gene showed modest association with absence of
      diabetic retinopathy. CONCLUSION: Our results suggest lack of association of
      PRKCB1 gene promoter polymorphisms and moderate protective association of PEDF
      gene polymorphism with DR in the south Indian population.

PMID- 20141355
TI  - Uveitis in DiGeorge syndrome: a case of autoimmune ocular inflammation in a
      patient with deletion 22q11.2.
AB  - PURPOSE: Del22q11.2, also known as DiGeorge syndrome, has a spectrum of ocular,
      facial and systemic features. Despite features of T cell dysfunction, infection
      and autoimmunity (including juvenile idiopathic arthritis), uveitis has not been
      described in patients with DiGeorge syndrome. METHODS: We describe a case of a 25
      year-old male with bilateral granulomatous panuveitis who after initial
      investigation and treatment for an infectious cause was determined to have
      autoimmune-related uveitis with evidence on clinical, laboratory and imaging
      assessments suggestive of ocular sarcoidosis. RESULTS: The patient was found to
      have a normal T cell count and T cell proliferative response that was compared to
      a control patient, and phenotypes determined by flow cytometry were normal.
      However, the CD4/CD8 ratio in this patient was slightly lower than normal and the
      number of CD28 negative T cells, in both CD4 and CD8 populations, were
      significantly higher than a control. CONCLUSIONS: The significance of these T
      cell abnormalities is unknown in the context of this patient's uveitis but is
      suggestive of a role in autoimmunity, which is a known phenomenon in del22q11.2
      syndrome, although autoimmune-related uveitis is not a previously described
      feature.

PMID- 20141356
TI  - Later retinal degeneration following childhood surgical aphakia in a family with
      recessive CRYAB mutation (p.R56W).
AB  - PURPOSE: To describe later retinal degeneration following childhood cataract
      surgery without intraocular lens implantation in a consanguineous family with
      developmental cataract from homozygous p.R56W mutation in CRYAB, a gene that
      encodes a heat-shock protein (alphaB-crystallin) in both retina and the lens.
      METHODS: Prospective ophthalmologic examination and venous blood sampling for
      diagnostic CRYAB sequencing in the 12 available family members (7 siblings and
      their 2 parents, the siblings' maternal aunt and her son, and the siblings'
      maternal grandmother). RESULTS: Those who underwent childhood cataract surgery (2
      siblings, their mother, their maternal aunt) or who had visually-insignificant
      lens opacities (2 siblings, their maternal grandmother) were homozygous for
      p.R56W CRYAB mutation. Among these 7 affected family members, clinically-obvious
      rod-cone degeneration was present only in the only 2 adults who were aphakic
      since childhood from cataract surgery. CONCLUSIONS: Recessive p.R56W CRYAB
      mutation shows variable expressivity for lens opacity. Decades of aphakia
      increases retinal light exposure and may be an environmental risk factor for
      significant retinal degeneration in patients homozygous for the mutation.

PMID- 20141357
TI  - Severe retinopathy of prematurity associated with FZD4 mutations.
AB  - PURPOSE: To determine whether mutations in the FZD4 gene are a risk factor for
      developing severe ROP. METHODS: Three Canadian tertiary care centers recruited
      premature infants prospectively and retrospectively, and assigned affectation
      status based on the maximum degree of severity of ROP recorded in both eyes.
      Mutation screening of the FZD4 gene was performed using direct sequencing. All
      sequence changes were evaluated for functional significance. RESULTS: Two novel
      FZD4 mutations (Ala370Gly or Lys203Asn) were identified in two infants from the
      severe ROP group (n=71). No mutation was detected in the mild to no ROP group
      (n=33), and the two novel mutations were absent in 173 random Caucasian samples.
      Mutation Ala370Gly was also found in one sibling and one parent of the affected
      infant, but no signs of familial exudative vitreoretinopathy (FEVR), a condition
      with phenotypic overlap with ROP known to be caused by FZD4 mutations, were
      present in either family member. CONCLUSIONS: Mutations in the FZD4 gene in this
      group of premature infants supports a role for the FZD4 pathway in the
      development of severe ROP and accounts for approximately 3% of severe ROP in
      Caucasian premature infants.

PMID- 20141358
TI  - Does acute loss of vision in autosomal dominant optic atrophy occur early in
      childhood?
AB  - PURPOSE: In contrast to Autosomal dominant optic atrophy (ADOA), acute loss of
      vision is normally observed in Leber's hereditary optic neuropathy (LHON)
      patients. We present a case of a young child with ADOA with a confirmed OPA1
      mutation who appeared to have had an acute visual loss in the third year of life.
      METHODS: Differentiating between ADOA and LHON requires careful documentation of
      visual symptoms, family history, clinical examination and genetic testing if
      available. CONCLUSIONS: This clarifies the clinical diagnosis, ensuring
      appropriate genetic counselling is provided so that affected individuals are
      accurately informed on inheritance patterns and implications for family members.

PMID- 20141359
TI  - Confirmation of ADAMTSL4 mutations for autosomal recessive isolated bilateral
      ectopia lentis.
AB  - Ectopia lentis (EL) is a zonular disease where alteration of the zonular fibers
      leads progressively to lens dislocation. It is most often associated with
      systemic diseases such as Marfan syndrome, Weill-Marchesani syndrome or
      homocystinuria. Isolated non syndromic ectopia lentis (IEL) is reported in
      families with autosomal inheritance, with dominant forms being more common than
      recessive. LTBP2 truncating mutations have been described as a cause of autosomal
      recessive ectopia lentis as a primary or secondary feature in patients showing
      ocular (eg, glaucoma) or extraocular manifestations (eg, Marfanoid habitus).
      Recently, ADAMTSL4 has been shown to be responsible for isolated autosomal
      recessive ectopia lentis in an inbred family. Herein we show a consanguineous
      family that carries a novel homozygous splice mutation IVS4-1G>A/IVS4-1G>A in
      ADAMTSL4 responsible for isolated autosomal recessive EL, thus confirming the
      involvement of this gene in this condition and underlining the major role of
      ADAMTS proteases in zonular fibers homeostasis.

PMID- 20141361
TI  - Periodontitis in psoriasis patients: a blinded, case-controlled study.
AB  - OBJECTIVE: Destructive periodontitis is one of the most frequent and widespread
      bacterial infections in humans. Psoriasis is a common condition in the general
      population. Since both psoriasis and periodontal diseases are characterized by an
      exaggerated response of the immune system to the epithelial surface microbiota,
      there may possibly be an association between these two conditions. The aim of the
      present pilot study was to investigate the prevalence of periodontal disease in
      psoriasis patients compared to healthy controls. MATERIAL AND METHODS: Dental
      bite-wing X-rays were obtained from 155 psoriasis patients aged 45-60 years, as
      well as from 155 age- and gender-matched controls. All X-rays were examined by
      the same investigator for accumulated destructive periodontitis using bone level
      and loss of teeth as endpoints. RESULTS: A significantly lower radiographic bone
      level (p < 0.001) and a significantly higher number of missing teeth (p < 0.001)
      were observed in the psoriasis cases compared to the controls. CONCLUSION: Our
      study indicates that psoriasis patients experience more bone loss than age- and
      gender-matched controls.

PMID- 20141362
TI  - What is an appropriate caries diagnosis?
AB  - This aim of this paper is to spur a discussion of the direction of caries-lesion
      detection activities in clinical dental practice. It is argued that since the
      dental clinician's caries-related decision making is a script-matching enterprise
      in which clinical decisions are made on the basis of 'this-lesion-needs-this-kind
      of-treatment' reasoning, the methods and strategies employed for caries lesion
      detection should accommodate this fact. This may be done by employing a clinical
      visual-tactile method for caries lesion detection that evaluates the two aspects
      that are crucial for appropriate caries management: lesion activity and surface
      integrity. The use of diagnostic methods that do not assess these features
      directly but involve assumptions about activity status and surface integrity
      should be avoided. This includes the use of bite-wing radiography for the
      detection of approximal caries lesions, as it may be shown that plain reliance on
      radiographs leads to considerable overtreatment. If clinical dentistry is to
      retain its status as a profession committed to doing good, changes in diagnostic
      practices along these lines are warranted.

PMID- 20141363
TI  - Temporomandibular disorders and oral health-related quality of life. A systematic
      review.
AB  - OBJECTIVE: Oral health-related quality of life (OHRQoL) is considered an
      important aspect of different oral conditions. It has also gained increased
      attention in temporomandibular disorders (TMDs) in recent years. The purpose of
      this study was to systematically review the literature on OHRQoL and TMDs.
      MATERIAL AND METHODS: A systematic search of the dental literature was performed
      using the Medline and Cochrane Library databases, supplemented by a hand search.
      Various combinations of search terms related to OHRQoL and TMDs were used. Among
      numerous titles found in Medline, abstracts and eventually full papers of
      potential interest were reviewed. Twelve papers fulfilled the inclusion criteria
      and were included in the review. RESULTS: Most studies used the Oral Health
      Impact Profile, an instrument with good psychometric properties, for evaluation.
      All articles described a substantial impact on OHRQoL in TMD patients. Only a
      small proportion of all patients, a few percent, reported no impact at all. The
      difference between men and women was small and not significant. The impact
      appeared to be more pronounced in patients with more signs and symptoms. The
      perceived impact of pain on OHRQoL seems to be substantial. Two studies found
      that the impact increased with age among TMD patients. CONCLUSIONS: The reviewed
      studies convincingly demonstrated that OHRQoL was negatively affected among TMD
      patients.

PMID- 20141364
TI  - Oral health and its influence on cognitive behavioral therapy in patients
      fulfilling the Diagnostic and Statistical Manual of Mental Disorders-IV criteria
      for intra-oral injection phobia.
AB  - OBJECTIVE: To describe self-perceived and clinically assessed oral health and
      oral treatment needs among intra-oral injection-phobic patients (Diagnostic and
      Statistical Manual of Mental Disorders-IV) and to explore whether these factors
      have an impact on the outcome of cognitive behavioral therapy (CBT). MATERIAL AND
      METHODS: Fifty-five patients (43 women, mean age 32.5 years, range 18-62 years)
      were treated with short-duration CBT. Dental anxiety (Dental Anxiety Scale and
      Dental Fear Survey) and self-perceived oral health were assessed by means of
      questionnaires. Three dentists assessed oral health by means of clinical
      examination and radiographs. Treatment outcome was measured by ability to receive
      an intra-oral injection by a general dentist within a 1-year follow-up (FU)
      period or ability to complete a behavioral avoidance test (BAT) at FU, and
      changes in dental anxiety and positive and negative thoughts from pretreatment to
      FU. RESULTS: Forty percent of patients ranged their oral health as "good" or
      "very good". Mean decayed teeth (DT) was 2.2 (range 0-15). The total number of
      teeth in need of treatment, periodontal treatment, endodontic treatment and
      extractions ranged from 0 to 15, 0 to 19, 0 to 4 and 0 to 5, respectively. Self
      rated oral health correlated significantly with clinical oral health. The outcome
      of CBT in terms of being able to receive a dental injection during FU was not
      influenced by oral health status. However, correlation analyses indicated that
      patients with the poorest oral health had the greatest increase in positive
      thoughts and the greatest decrease in negative thoughts from pretreatment to FU.
      CONCLUSIONS: The oral health of intra-oral injection-phobic patients varies
      substantially, but is comparable to that of the normal population. Coping with a
      dental injection after CBT is not influenced by oral health and treatment needs.

PMID- 20141365
TI  - Work flow with digital intraoral radiography: a systematic review.
AB  - OBJECTIVE: This systematic review evaluates the six most frequently emphasized
      advantages of working with digital radiography: less working time, lower
      radiation dose to the patient, fewer retakes and errors, wider dynamic range,
      easier access to patient information and easier image storage and communication.
      Moreover, some clinical aspects and possible disadvantages of digital imaging
      that were not foreseen at the beginning of the digital era, such as patient
      discomfort, damage to the receptor, degradation of the image, cross-contamination
      and viewing conditions, were assessed. MATERIAL AND METHODS: The literature
      search used the PubMed database with no limits and was performed during June to
      August 2009. Search strategies are described in the text for each of the
      mentioned tasks. A hand search of task-specific journals supplemented the search
      strategies. RESULTS: Time seems to be saved when switching from film to digital
      imaging in dental practice, a dose reduction may not be obtained, retakes and
      errors may be increased, the dynamic range may be wider with photostimulable
      storage phosphor (PSP) plates but not with sensors, the effect on patient
      information has not been well studied and storage and communication create new
      challenges with regard to handling large files and image compression. In
      addition, patient discomfort seems to be pronounced with sensors compared with
      PSP plates and film, the PSP plate may be scratched in clinical use and a two
      layer barrier seems to be needed to prevent contamination of the receptor. The
      type of monitor may not be of major concern if the image is viewed in a room with
      subdued light. CONCLUSIONS: Not all of the predicted advantages with digital
      compared to film-based radiography hold true in daily clinical work. Of
      particular interest is the relationship between number of images, retakes and the
      dose given to the patient.

PMID- 20141366
TI  - Comparison of two different microbiological test kits for detection of
      periodontal pathogens.
AB  - OBJECTIVE: The aim of this study was to compare the outcome of two different
      microbiological tests for detection of Aggregatibacter actinomycetemcomitans
      (A.a.), Porphyromonas gingivalis (P.g.), Tannerella forsythia (T.f.) and
      Treponema denticola (T.d.). MATERIAL AND METHODS: A total of 69 adult patients
      with severe chronic (sCP) or aggressive periodontitis (AgP) participated in the
      study. Microbiological samples were examined for A.a., P.g., T.f. and T.d. using
      an RNA probe test (PADO) and a real-time polymerase chain reaction test (MERI).
      RESULTS: For all periodontal pathogens under investigation, the median bacterial
      counts detected with PADO were smaller compared to those detected with MERI.
      P.g., T.f. and T.d. could be found in the majority of all patients with both
      tests. With MERI, A.a. was detected more often (24.6%) than with PADO (18.8%).
      Only 10.1% of the patients tested positive for A.a. with both tests. CONCLUSION:
      Both tests showed a high percentage of agreement for P.g., T.f. and T.d., but
      exhibited marked differences in the detection of A.a.

PMID- 20141367
TI  - Response to oral bisphosphonates in subgroups of younger and older postmenopausal
      women.
AB  - BACKGROUND: Although the effects of bisphosphonates in bone are known for
      postmenopausal women, it is not known if younger postmenopausal women have a
      similar response. Furthermore, it is not known if the effects of alendronate and
      risedronate differ in postmenopausal women in regard to age, specifically in
      women at or younger than the mean age of natural menopause. Our aim was to
      examine the effects of two oral bisphosphonates in postmenopausal women by age.
      METHODS: This was a post-hoc analysis of postmenopausal women <55 or > or =55
      years old with low bone mineral density (BMD), randomized to once weekly
      alendronate 70 mg or risedronate 35 mg for 1 year with 1-year extensions in U.S.
      and International Fosamax Actonel Comparison Trials. RESULTS: In both age
      subgroups of postmenopausal women, alendronate produced significantly greater
      mean BMD increases from baseline than risedronate at hip trochanter, lumbar
      spine, total hip, and femoral neck. Changes in BMD were not significantly
      different between younger and older alendronate-treated women, although treatment
      differences favoring alendronate were numerically greater for younger than older
      postmenopausal women at all sites. Significantly greater reductions in bone
      turnover markers also occurred with alendronate vs. risedronate in both
      subgroups. Tolerability was similar between treatments. CONCLUSIONS: In this post
      hoc subgroup analysis of older and younger postmenopausal women receiving
      alendronate or risedronate, larger treatment differences in BMD gain in younger
      compared with older women suggest that patient age may affect the relative
      efficacy of these antiresorptive drugs.

PMID- 20141368
TI  - Effects of 17beta-oestradiol and norethisterone acetate on sulfonation and
      sialylation of gonadotrophins in post-menopausal women.
AB  - BACKGROUND: The number of terminal sialic acid and sulfonated N
      acetylgalactosamine (SO(3)-GalNAc) on gonadotrophins in serum varies during the
      menstrual cycle and changes at menopause, suggesting that gonadal steroids modify
      their oligosaccharide synthesis. Our objective was to determine the effects of
      17beta-oestradiol (E(2)) and a progestogen, norethisterone acetate (NETA), on the
      sulfonation and sialylation of gonadotrophins in post-menopausal women. METHODS:
      Serum samples were obtained from eight post-menopausal women treated with 20 mg
      E(2) implants every 6 months, from four women who in addition were treated daily
      with 5 mg NETA orally for a 2-week period, and from four women who got this NETA
      treatment during a 4-week period. Sera from 11 non-treated post-menopausal women
      served as a reference group. The gonadotrophin serum concentrations, the number
      of SO(3)-GalNAc and sialic acid residues per serum luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH) molecule, and the distributions of molecules
      with 0-1-2-3-4 sulfonated residues were measured. RESULTS: The E(2)-treated post
      menopausal women had considerably less (P < 0.001) sialic acid and slightly more
      (P < 0.01) SO(3)-GalNAc per serum LH and FSH molecule than the non-treated. Two
      weeks of NETA treatment increased the sulfonation of LH (P < 0.01) and FSH (P <
      0.05) concomitantly with decreased (P < 0.05) sialylation of LH. CONCLUSION: The
      primary effect of E(2) treatment was a decrease in sialylation and, due to
      competition for the same substrate, a secondary and consequentially minor
      increase in sulfonation of LH and FSH. The primary effect of the NETA therapy was
      an increase in the sulfonation of LH and FSH concomitantly with secondary and
      consequentially decreases in sialylation of LH.

PMID- 20141369
TI  - Epidemiology of fertility treatment use among U.S. women with liveborn infants,
      1997-2004.
AB  - OBJECTIVE: This study assessed reported use of assisted reproductive technology
      (ART) and other (non-ART) fertility treatments among a population-based sample
      and examined factors related to use. METHODS: The data for this study were
      collected as part of the National Birth Defects Prevention Study (NBDPS), limited
      to women from the control group who delivered liveborn infants with no major
      birth defects. We described prevalence of the use of ART and clomiphene citrate
      (the most commonly used non-ART treatment) by demographic and lifestyle factors
      and examined associations among use of fertility treatments and pregnancy
      outcomes, timing of prenatal care initiation, and use of prenatal testing
      technologies. RESULTS: Overall, 4.2% of women reported any type of maternal
      fertility treatment use; 1.0% reported ART use, 1.6% reported clomiphene citrate
      use without ART, and 1.7% reported other fertility treatments. Women who reported
      any fertility treatment type were more likely than women with an unassisted
      conception to be non-Hispanic white, >30 years of age, and more highly educated.
      Overall, women who reported ART use were more likely than women who reported
      unassisted pregnancy to have an amniocentesis; however, this association was no
      longer evident after adjustment for maternal age. CONCLUSIONS: Fertility
      treatment use and type of treatment vary by maternal characteristics. This
      information may be useful to inform a broad maternal and child health audience
      about the growing use of fertility treatments, including who is using the
      treatments and the choices they are making about prenatal care.

PMID- 20141370
TI  - Medicaid and preterm birth and low birth weight: the last two decades.
AB  - OBJECTIVES: To determine if (1) birth outcomes among women on Medicaid differ
      significantly from outcomes of those with private insurance, after controlling
      for known risk factors, and (2) enhanced prenatal care influences care use and
      birth outcomes. METHODS: This is a review of studies published between 1989 and
      2009 that examined birth outcomes (1) between women on Medicaid and those with
      private insurance and (2) among Medicaid enrollees who received comprehensive
      prenatal care. RESULTS: When corrected for risk variables, birth outcomes are not
      different between private insurance and Medicaid patients. The impact of
      comprehensive prenatal care programs on birth outcomes varies across states and
      regions. CONCLUSIONS: There is a need for critical evaluation of comprehensive
      programs in a regional and state context to determine opportunities for
      improvement.

PMID- 20141371
TI  - Spores of Mucor ramosissimus, Mucor plumbeus and Mucor circinelloides and their
      ability to activate human complement system in vitro.
AB  - Complement activation by spores of Mucor ramosissimus, Mucor plumbeus and Mucor
      circinelloides was studied using absorbed human serum in the presence or absence
      of chelators (EGTA or EDTA). We found that the spore caused full complement
      activation when incubated with EGTA-Mg2+ or without chelators, indicating that
      the alternative pathway is mainly responsible for this response. In order to
      compare activation profiles from each species, ELISAs for C3 and C4 fragments,
      mannan binding lectin (MBL), C-reactive protein (CRP) and IgG studies were
      carried out. All proteins were present on the species tested. Immunofluorescence
      tests demonstrated the presence of C3 fragments on the surface of all samples,
      which were confluent throughout fungal surfaces. The same profile of C3, C4, MBL,
      CRP and IgG deposition, observed in all species, suggests a similar activation
      behavior for these species.

PMID- 20141372
TI  - The distribution of species and susceptibility of amphotericin B and fluconazole
      of yeast pathogens isolated from sterile sites in Taiwan.
AB  - To study the demographic changes of yeasts causing invasive infections in Taiwan,
      especially with respect to species distribution and antifungal susceptibility, we
      analyzed isolates obtained from four sterile sites of patients in 19 hospitals in
      2002 (155 strains) and again from the same hospitals in 2006 (208 strains). Blood
      was the most common source of the yeasts, accounting for 73.8% of the total
      isolates, followed by ascites (21.5%), cerebrospinal fluid (3%), and synovia
      (1.7%). Candida albicans was the most frequently recovered species (50.1% of the
      total), followed by Candida tropicalis (20.7%), Candida glabrata (11.6%), Candida
      parapsilosis (8.5%), Cryptococcus neoformans (3.9%), Candida krusei (0.8%), and
      nine other species (4.3%). There were one (0.3%) and seven (1.9%) isolates with
      minimum inhibitory concentrations (MICs) of amphotericin B > or =2 mg/l after 24
      h and 48 h incubation, respectively. In addition, there were 15 (4.3%) and 31
      (8.6%) isolates with MICs of fluconazole > or =64 mg/l under the same conditions.
      The MIC(90) value of amphotericin B was 1 mg/l. The MIC(90) values of fluconazole
      were 4 mg/l after 24 h incubation and 32 mg/l after 48 h incubation.
      Interestingly, MICs for fluconazole > or =64 mg/l after 24 h were significantly
      higher for isolates obtained in 2006 than those in 2002 after 24 h (7.1% vs.
      0.7%, p =0.009) and 48 h (13.5% vs. 2%, p =0.0003) incubations. The demographic
      difference between these two surveys is mainly due to one species, C. tropicalis.

PMID- 20141373
TI  - Phialosimplex, a new anamorphic genus associated with infections in dogs and
      having phylogenetic affinity to the Trichocomaceae.
AB  - Anamorphic members of the ascomycete family Trichocomaceae including Aspergillus,
      Penicillium, Paecilomyces, Geosmithia and Sagenomella have been reported from
      infections in canines. Six clinical isolates (five associated with infections in
      canines and one from a human source) demonstrated simple phialides producing
      conidia in long chains and were investigated for their potential relationship to
      Sagenomella chlamydospora, a known agent of canine disseminated mycosis.
      Phylogenetic analyses of internal transcribed spacer (ITS) and small subunit
      (SSU) region sequences revealed that all of the canine-associated isolates were
      distinct from Sagenomella species. The new anamorphic genus and species
      Phialosimplex caninus is described to accommodate the clinical isolates.
      Sagenomella chlamydospora and Sagenomella sclerotialis are transferred to the new
      genus as Phialosimplex chlamydosporus comb. nov. and Phialosimplex sclerotialis
      comb. nov.

PMID- 20141374
TI  - Arthrographis kalrae, a rare causal agent of onychomycosis, and its occurrence in
      natural and commercially available soils.
AB  - We report a rare case of onychomycosis due to Arthrographis kalrae, and describe
      an attempt to elucidate the source of the infection by fungal isolation and PCR
      based methods for detection of A. kalrae. The patient was a 63-year-old Japanese
      man, whose fingernails, excluding the right index finger, were markedly
      dystrophic. Microscopic examination of his fingernails disclosed hyaline hyphae
      and arthroconidia. The causal agent was identified as A. kalrae based on
      morphological characteristics and ITS region sequencing. The fungus was
      susceptible in vitro to terbinafine, itraconazole, and miconazole. A therapeutic
      trial of oral terbinafine, 125 mg/day and topical 1% miconazole for seven months
      brought about a complete cure of the ungual lesion. We found that A. kalrae could
      be detected at 1.1 x 10(4) CFU/g (92.4% incidence) in soil from the patient's
      garden. Furthermore, varying CFUs of A. kalrae were recovered in 61% of the
      samples obtained from crop field soils, commercially available soils or allied
      products for gardening. Since the patient was working with soil that harbored A.
      kalrae, the possibility of acquiring the infection from this source should not be
      excluded.

PMID- 20141375
TI  - Candidal abscess of the parotid gland due to Candida glabrata: report of a case
      and literature review.
AB  - We report the case of an immunocompetent woman who developed a Candida glabrata
      abscess of the parotid gland and present a review of similar cases from the
      literature. Diagnosis was based on the isolation of C. glabrata in pure culture
      from the abscess pus. Examination of stained smears of the same material
      demonstrated small sized yeast cells, some being intra-macrophagic. Combination
      of a local drainage and oral fluconazole proved to be an efficient therapeutic
      strategy. Candidal abscesses are rare in immunocompetent patients and salivary
      gland localization has only been reported in five cases.

PMID- 20141377
TI  - Differences in tissue drug concentrations following intravenous versus
      intraperitoneal treatment with amphotericin B deoxycholate or liposomal
      amphotericin B.
AB  - Amphotericin B formulations were compared in preclinical models by using
      intraperitoneal (ip) and intravenous (iv) delivery of amphotericin B deoxycholate
      (DAMB) or liposomal amphotericin B. We examined the effects on drug tissue
      penetration and retention resulting from different routes of drug administration.
      Mice were treated with equivalent total doses of AmBisome (AmBi) or DAMB (i.e.,15
      mg/kg) given ip (3 mg/kg/day for 5 days) or iv (3 mg/kg/day AmBi for 5 days or 1
      mg/kg/day DAMB for 15 days), with tissues collected 24 h post-treatment. For drug
      retention studies, mice were given iv or ip total doses of 30 mg/kg AmBi (10
      mg/kg/day 3 x /week) or 60 mg/kg AmBi (20 mg/kg/day 3 x /week) with tissue
      collection 24 h or 7 days post-treatment. Blood samples were collected at 0.5 h,
      2 h, 8 h, 12 h and 24 h after ip or iv drug dosing. A Paecilomyces variottii
      bioassay was used to determine drug concentrations. AmBi and DAMB were detected
      in the kidneys following iv, but not ip dosing. Significantly more DAMB than AmBi
      was detected in the lungs with ip dosing (P = 0.008), and more AmBi than DAMB (P
      = 0.056) was present with iv dosing. Unlike the lungs, the spleen and liver
      retained the AmBi for up to one week post-treatment regardless of the route of
      drug administration. Thus, there are significant differences in AmBi and DAMB
      tissue distribution depending upon the drug route and these differences could
      effect how the drugs perform in fungal infection models.

PMID- 20141378
TI  - The impact of delaying the initiation of appropriate antifungal treatment for
      Candida bloodstream infection.
AB  - We performed a retrospective analysis of the time to initiation of appropriate
      antifungal therapy for candidemia and in-hospital mortality. The definition of
      appropriate antifungal therapy was based on in vitro susceptibility results, and
      in the case of fluconazole, pharmacodynamic parameters. Of 123 patients, the
      mortality rate in the <24 h, 24-48 h, and >48 h groups was 50%, 28%, and 32%,
      respectively. Patients who never received antifungal treatment had a 61%
      mortality rate (difference between groups, P =0.06). Multivariate analysis found
      APACHE II score (AOR = 1.09, 95% CI: 1.02-1.17 for each point increase) to be the
      only independent predictor of mortality. The time to initiation of appropriate
      antifungal therapy did not correlate with in-hospital mortality.

PMID- 20141380
TI  - A cost-effectiveness analysis of MMX mesalazine compared with mesalazine in the
      treatment of mild-to-moderate ulcerative colitis from a UK perspective.
AB  - OBJECTIVES: To perform a cost-utility analysis of a new formulation of mesalazine
      (Mezavant XL, MMX mesalazine) versus an existing oral mesalazine (Asacol;
      mesalazine) from the UK National Health Service perspective. METHODS: A 5-year
      Markov cohort model was developed. Costs were obtained from the literature and
      utilities from an independent study. Uncertainty was evaluated using one-way and
      probabilistic sensitivity analyses (PSA). The potential effect of dosing
      frequency on adherence and possible long-term effects of remission maintenance on
      colorectal cancer (CRC) rates were also investigated. RESULTS: The model
      suggested that 5-year therapy with MMX mesalazine was likely to generate gains
      when compared with mesalazine, including a gain of 0.011 QALYs per patient, 19
      more remission days, and 12% fewer hospitalizations and surgical episodes. These
      gains came at an increase in total NHS direct cost of L8, resulting in an
      incremental cost-effectiveness ratio (ICER) of L749. The PSA suggested that MMX
      mesalazine had a 62% chance of resulting in cost savings, and a 74% chance of
      being cost-effective (L20,000 threshold). Extended analysis including adherence
      and CRC effects suggested further incremental benefit of MMX mesalazine over
      mesalazine could be expected. Limitations include uncertainty in extrapolation to
      a 5-year time horizon and impact of adherence and drug acquisition costs on
      outcomes. CONCLUSION: The pharmacoeconomic analysis suggested that MMX mesalazine
      is likely to produce small, but worthwhile, increases in total NHS direct cost
      while increasing time in remission and associated quality of life, when compared
      with mesalazine. Advantages in adherence to treatment with MMX mesalazine
      relative to mesalazine suggested that further health gains and cost savings can
      be obtained. Overall, these results suggest that MMX mesalazine is a cost
      effective treatment for UC.

PMID- 20141381
TI  - Economic impact of switching from valsartan to other angiotensin receptor
      blockers in patients with hypertension.
AB  - BACKGROUND: The approaching availability of lower-cost generic angiotensin
      receptor blockers (ARBs) may affect formulary policies for patients maintained on
      the ARB valsartan. OBJECTIVE: Estimate the economic impact of switching from
      valsartan (including valsartan-based single-pill combinations) to other ARBs
      without apparent medical reasons. RESEARCH DESIGN AND METHODS: Patients with
      essential hypertension and at least 6 months of continuous valsartan treatment
      free of hospitalization, cardiovascular events, renal events or ARB-associated
      adverse events were identified from the MarketScan administrative claims database
      from January 1, 2004 to March 31, 2008. Those who subsequently switched to a
      different ARB with at least a 5% copayment decrease (switchers) were matched to
      those who did not switch (maintainers) according to propensity score quintiles
      and selected baseline characteristics. Refills were not required after the index
      fill for the switched-to ARB or maintained valsartan. Matched switchers and
      maintainers were compared in terms of medication discontinuation, healthcare
      resource use and costs during the 6 months following the index fill. RESULTS: A
      total of 99,926 valsartan maintainers and 2150 switchers (with a mean copayment
      decrease of $16.5 per month) were identified and matched. After matching,
      switching from versus maintaining valsartan was associated with an 8% higher risk
      of medication discontinuation (p < 0.008), 19.1 additional outpatient visits/100
      patients (p = 0.002) and 9.3 additional hypertension-related inpatient days/100
      patients (p = 0.030). Concurrently, switching from versus maintaining valsartan
      was associated with higher total medical costs by $748/patient (p < 0.001),
      driven largely by higher costs for hypertension-related medical services by
      $492/patient (p = 0.004). LIMITATIONS: Exact reasons for switching were not
      available and the study assessed only the short-term impacts of switching.
      CONCLUSIONS: Hypertension patients maintained on valsartan who switched to a
      different ARB with a lower copayment experienced substantial increases in
      medication discontinuation, healthcare resource use and costs compared to those
      who maintained valsartan treatment.

PMID- 20141382
TI  - Invasive and in situ cervical cancer reported to the vaccine adverse event
      reporting system (VAERS).
AB  - The quadrivalent human papillomavirus (HPV) vaccine was recommended in 2006 for
      routine vaccination of 11 or 12-year-old girls, with catchup through age 26
      years, for the prevention of genital HPV-related diseases. The Vaccine Adverse
      Event Reporting System (VAERS) is a national spontaneous surveillance system of
      adverse events following vaccination in the United States. The objective of this
      study was to identify and review VAERS reports of invasive and in situ cervical
      cancer in women immunized with the quadrivalent HPV vaccine. A VAERS database
      search was performed to identify such cases reported in the United States from
      January 1, 2006, through April 9, 2009. Medical Dictionary for Regulatory
      Activities (MedDRA) search terms used were "cervix carcinoma," "cervix carcinoma
      stage 0," "cervix carcinoma stage III," "carcinoma in situ," and "cervical
      dysplasia." Case inclusion required a report to contain a clear statement of a
      cervical carcinoma or carcinoma in situ diagnosis on any screening or diagnostic
      test after at least one dose of the HPV vaccine. All reports were reviewed by two
      investigators. Four VAERS reports for MedDRA term "cervix carcinoma," one for
      "cervix carcinoma stage 0," none for "cervix carcinoma stage III," three for
      "carcinoma in situ," and 53 for "cervical dysplasia" were identified. Of these,
      three cases of carcinoma in situ and one case of microinvasive cervical cancer
      met study inclusion criteria. Cases of cervical cancer and precancers are not
      unexpected in vaccinated women. Cervical cancer screening continues to be
      important, even for women who have received the HPV vaccine.

PMID- 20141383
TI  - Alleviating distress during antepartum hospitalization: a randomized controlled
      trial of music and recreation therapy.
AB  - BACKGROUND: Pregnant women who are placed on hospitalized bed rest experience
      increased antepartum-related distress. We sought to examine the efficacy of a
      single session music or recreation therapy intervention to reduce antepartum
      related distress among women with high-risk pregnancies experiencing extended
      antepartum hospitalizations. METHODS: In a randomized, single-blinded study,
      participants (n = 80) received 1 hour of music or recreation therapy or were
      placed in an attention-control group. Antepartum-related distress was measured by
      the Antepartum Bedrest Emotional Impact Inventory, which was administered before
      and after the intervention and at a follow-up period between 48 and 72 hours.
      RESULTS: Significant associations were found between the delivery of music and
      recreation therapy and the reduction of antepartum-related distress in women
      hospitalized with high-risk pregnancies. These statistically significant
      reductions in distress persisted over a period of up to 48-72 hours. CONCLUSIONS:
      Single session music and recreation therapy interventions effectively alleviate
      antepartum-related distress among high-risk women experiencing antepartum
      hospitalization and should be considered as valuable additions to any
      comprehensive antepartum program.

PMID- 20141384
TI  - Predictors of screening mammography among Asian Indian American women: a cross
      sectional study in the Baltimore-Washington metropolitan area.
AB  - OBJECTIVE: To assess adherence to screening mammography guidelines and examine
      predictors of having a mammogram in the past 2 years among immigrant Asian Indian
      women (AIW) aged > or = 40 years. METHODS: Face-to-face surveys of 418 AIW in the
      Baltimore-Washington metropolitan area were conducted. Subjects were recruited
      through Asian Indian (AI) religious and other community-based organizations.
      RESULTS: Of the 418 AIW surveyed, 83% had ever had a mammogram, and 70% had
      obtained a mammogram within the past 2 years. AIW who had lived in the United
      States for > 10 years had a higher rate of obtaining a mammogram (75.4%) within
      the past 2 years than did those who had lived in the United States for < or = 10
      years (24.6%). In multiple logistic regression analysis, length of stay in the
      United States, marital status, knowledge of mammogram guidelines, age, having
      health insurance, physician recommendations, and number of relatives who had a
      mammogram were positively associated with having a mammogram within the past 2
      years. Physician ethnicity and not having a healthcare provider were negatively
      associated with having a mammogram within the past 2 years. CONCLUSIONS: This
      study lays a foundation for designing guidelines for interventions to improve
      mammography screening behaviors among AIW women. Increasing the use of mammogram
      to the levels recommended by guidelines will require a two-pronged approach
      directed at both AIW and AI physicians.

PMID- 20141385
TI  - Hierarchy as a barrier to advancement for women in academic medicine.
AB  - BACKGROUND: Research on barriers to professional advancement for women in
      academic medicine has not adequately considered the role of environmental factors
      and how the structure of organizations affects professional advancement and work
      experiences. This article examines the impact of the hierarchy, including both
      the organization's hierarchical structure and professionals' perceptions of this
      structure, in medical school organization on faculty members' experience and
      advancement in academic medicine. METHODS: As part of an inductive qualitative
      study of faculty in five disparate U.S. medical schools, we interviewed 96
      medical faculty at different career stages and in diverse specialties, using in
      depth semistructured interviews, about their perceptions about and experiences in
      academic medicine. Data were coded and analysis was conducted in the grounded
      theory tradition. RESULTS: Our respondents saw the hierarchy of chairs, based on
      the indeterminate tenure of department chairs, as a central characteristic of the
      structure of academic medicine. Many faculty saw this hierarchy as affecting
      inclusion, reducing transparency in decision making, and impeding advancement.
      Indeterminate chair terms lessen turnover and may create a bottleneck for
      advancement. Both men and women faculty perceived this hierarchy, but women saw
      it as more consequential. CONCLUSIONS: The hierarchical structure of academic
      medicine has a significant impact on faculty work experiences, including
      advancement, especially for women. We suggest that medical schools consider
      alternative models of leadership and managerial styles, including fixed terms for
      chairs with a greater emphasis on inclusion. This is a structural reform that
      could increase opportunities for advancement especially for women in academic
      medicine.

PMID- 20141386
TI  - Protein-engineered biomaterials: highly tunable tissue engineering scaffolds.
AB  - A common goal in tissue engineering is to attain the ability to tailor specific
      cell-scaffold interactions and thereby gain control over cell behavior. The
      tunable nature of protein-engineered biomaterials enables independent tailoring
      of a range of biomaterial properties, creating an attractive alternative to
      synthetic polymeric scaffolds or harvested natural scaffolds. Protein-engineered
      biomaterials are comprised of modular peptide domains with various
      functionalities that are encoded into a DNA plasmid, transfected into an organism
      of choice, and expressed and purified to yield a biopolymer with exact molecular
      level sequence specification. Because of the modular design strategy of protein
      engineered biomaterials, these scaffolds can be easily modified to enable
      optimization for specific tissue engineering applications. By including multiple
      peptide domains with different functionalities in a single, modular biomaterial,
      the scaffolds can be designed to mimic the diverse properties of the natural
      extracellular matrix, including cell adhesion, cell signaling, elasticity, and
      biodegradability. Recently, the field of protein-engineered biomaterials has
      expanded to include functional modules that are not normally present in the
      extracellular matrix, thus expanding the scope and functionality of these
      materials. For example, these modules can include noncanonical amino acids,
      inorganic-binding domains, and DNA-binding sequences. The modularity, tunability,
      and sequence specificity of protein-engineered biomaterials make them attractive
      candidates for use as substrates for a variety of tissue engineering
      applications.

PMID- 20141387
TI  - Neocartilage formation in 1 g, simulated, and microgravity environments:
      implications for tissue engineering.
AB  - AIM: The aim of this study was to analyze and compare the deposition of cartilage
      specific extracellular matrix components and cellular organization in scaffold
      free neocartilage produced in microgravity and simulated microgravity. METHODS:
      Porcine chondrocytes were seeded (100 x 10(6)/mL) into cylindrical culture
      chambers (n = 8) and cultured in the following environments: (i) microgravity
      during the Flight 7S (Cervantes mission) on the International Space Station
      (ISS), (ii) simulated microgravity in a random positioning machine (RPM), and
      (iii) normal gravity (1 g, control). After 16 days, each neocartilage tissue was
      processed for histology, immunohistochemistry, quantitative real-time reverse
      transcriptase-polymerase chain reaction, and histomorphometric analysis. RESULTS:
      Weaker extracellular matrix staining of ISS neocartilage tissue was noted
      compared with both Earth-cultivated tissues. Higher collagen II/I expression
      ratios were observed in ISS samples compared with control tissue. Conversely,
      higher aggrecan/versican gene expression profiles were seen in control 1 g
      samples compared with microgravity samples. Cell density produced in microgravity
      was significantly reduced compared with the normal gravity neocartilage tissues.
      CONCLUSION: Tissue cultivated on the RPM showed intermediate characteristics
      compared with ISS and 1 g conditions. These data indicate that the RPM system
      does not sustain microgravity. Although microgravity impacts the development of
      in vitro generated cartilage, simulated microgravity using the RPM may be a
      useful tool to produce cartilaginous tissue grafts with fewer cells.

PMID- 20141388
TI  - An update on the pathogenesis, inflammation, and metabolism in hirsutism and
      polycystic ovary syndrome.
AB  - Hirsutism is a common endocrine disorder, defined as increased growth of terminal
      hairs in a male pattern. Hirsutism is most often caused by polycystic ovary
      syndrome (PCOS), whereas only 5% patients are diagnosed with rare endocrine
      diseases. PCOS may be considered a multiorgan disease causing not only increased
      adrenal and ovarian sex hormone secretion but also changed secretion of
      gonadotrophins, growth hormone, and adrenocorticotrophic hormone (ACTH) from the
      pituitary. The majority of patients with PCOS are insulin resistant and PCOS is
      characterized by an increased inflammatory state with abdominal obesity and
      increased secretion of interleukins, chemokines, and adipokines. PCOS is
      therefore associated with an increased risk of the metabolic syndrome and type 2
      diabetes (T2D). Patients with hirsutism present with increased bone mineral
      density despite decreased D-vitamin levels. The etiology to hirsutism and PCOS is
      most likely multifactorial including both genetic and environmental factors such
      as increased fetal stress and intrauterine growth retardation. In the present
      review, we give a comprehensive overview of the pathophysiology and multiple
      endocrine disturbances of hirsutism and PCOS.

PMID- 20141389
TI  - Substance use and survival after treatment for chronic myelogenous leukemia (CML)
      or myelodysplastic syndrome (MDS).
AB  - BACKGROUND: Patients' substance use problems are a particularly understudied
      aspect of psychosocial variables in cancer treatment. OBJECTIVES: The specific
      hypothesis tested was that lifetime substance use disorders increased the risk of
      adverse outcome, in the context of other psychosocial and clinical
      characteristics demonstrated in other studies to have an impact on treatment
      outcome. METHOD: Prospective cohort study of 106 adults with chronic myelogenous
      leukemia or primary myelodysplastic syndrome. None satisfied criteria for current
      substance abuse or dependence, but the lifetime rates of substance use disorders
      in this sample were 28% for alcohol, 12% for cannabis, and 9% for cocaine.
      RESULTS: Participants received treatment as directed by their physicians, and
      were followed until death or the end of the study (median 1.5 years). Twenty
      eight died. Multivariate survival analysis identified three predictors of
      outcome: lifetime cocaine use, associated with a six-fold increased risk of death
      (p = .04), and two protective variables, baseline hemoglobin (p = .002) and
      estimated intelligence quotient (IQ) (p = .04). CONCLUSION: The results of this
      study highlight the potential significance of substance use disorders, and
      lifetime cocaine diagnoses in particular, on treatment outcome for people with
      chronic myelogenous leukemia or myelodysplastic syndrome. Whereas neither
      lifetime alcohol nor cannabis use were associated with survival on either the
      univariate or multivariate models of survival, lifetime cocaine diagnoses were
      associated with significant six-fold increased risk of death (p = .04).

PMID- 20141390
TI  - Impact of self-reported life events on the profile of opioid dependence syndrome.
AB  - AIM: The aim of this work was to investigate the impact of life events on the
      profile of opioid dependent patients. METHOD: Recruitment was achieved through
      outpatient drug treatment clinic in Birmingham, UK, and data were collected
      through semistructured interviews. One-hundred and twenty subjects with opioid
      dependence syndrome were interviewed, and 100 controls of non-drug-using family
      members and friends. RESULT: The mean age of the opioid group was 33.3 years, SD
      = 8.8. The majority individuals of the sample were White British (80.8%),
      unemployed (69.2%), and male (75%). The mean severity of dependence as measured
      by two scales indicated severe level of dependence according to the authors of
      each scale. The mean number of traumatic events for the opioid dependence group
      was 4.8, SD = 3.57 vs. 3.55; SD = 3.65 in control group with significant
      difference (t = 2.56, df = 218, p = .01). Significant predictors of severe opioid
      dependency were age of second exposure to events, change of residence, break-up
      with boy/girlfriend, and conflict with father. CONCLUSION: The data presented
      indicate that a significant group of opioid dependent patients experience adverse
      life events in both childhood and adulthood. It is by attending to and addressing
      these issues that health care workers can alleviate ongoing distress and promote
      confidence.

PMID- 20141391
TI  - Isoprostane as a marker of oxidative stress in chronic heroin users: correlation
      with duration of heroin use or concomitant hepatitis C infection.
AB  - BACKGROUND: Although chronic heroin abuse has been extensively linked to
      oxidative stress, and while plasma 15-F(2t)-IsoP is considered a good indicator
      of oxidative stress, there remain few references in the literature about the
      plasma concentration of this marker in heroin dependent subjects. OBJECTIVES: To
      determine plasma 15-F(2t)-IsoP, as a marker of oxidative stress, in chronic
      heroin users, and to examine whether the values of this marker correlate with the
      duration of heroin use or with the presence of anti-HCV antibodies. METHODS:
      Forty-two chronic heroin users and twenty two healthy control subjects were
      recruited for this study. An enzyme-immunoassay method was used for the
      determination of 15-F(2t)-IsoP in plasma. RESULTS: Plasma 15-F(2t)-IsoP values
      were significantly higher in chronic heroin users compared to healthy controls.
      No correlation was found between the values of plasma 15-F(2t)-IsoP and the
      duration of heroin use. Heroin dependent subjects positive for anti-HCV
      antibodies had significantly lower values of plasma 15-F(2t)-IsoP as compared to
      those without a history of HCV infection. CONCLUSIONS: The elevated plasma 15
      F(2t)-IsoP values in heroin dependent subjects, compared to healthy individuals,
      indicate a shift of the balance between oxidants and antioxidants towards the
      former and suggest that heroin dependent subjects could benefit from an
      antioxidant therapy.

PMID- 20141392
TI  - Gender differences in social support and depression among injection drug users in
      Houston, Texas.
AB  - BACKGROUND: Injection drug is the second most frequent HIV/AIDS exposure in the
      United States. Social support and depression may mediate risky behaviors among
      drug injectors. OBJECTIVES: To describe differences in perceived social support
      and depressive symptoms between male and female injection drug users, and to
      describe factors associated with depressive symptoms. METHODS: Using respondent
      driven sampling, we recruited and interviewed injection drug users in Houston,
      Texas. Data were from the Centers for Disease Control and Prevention's National
      HIV Behavioral Surveillance Program. We used the short Center for Epidemiologic
      Studies Depression Scale (CES-D 10) and scales for perceived social support from
      family, friends, and significant others from the Multidimensional Scale of
      Perceived Social Support. Four-hundred seventy-one participants had complete data
      and were included in this analysis. RESULTS: Seventy-five percent of male and
      female participants had CES-D scores indicating depressive symptoms. In a
      multivariate logistic regression, depressive symptoms among men were positively
      associated with frequent use of speedballs (injecting heroin and cocaine
      together) and never having tested for HIV, and negatively associated with
      perceived social support from a special person. Among women, depressive symptoms
      were positively associated with currently smoking cigarettes, having no health
      insurance, and more years of injection drug use, and negatively associated with
      perceived social support from a special person. CONCLUSIONS: Lack of social
      support from a special person or significant other was associated with depressive
      symptoms in both males and females. Our findings suggest that depression and
      social support should be addressed when developing HIV prevention programs among
      injection drug users.

PMID- 20141393
TI  - Addiction severity index composite scores as predictors for sexual-risk behaviors
      and drug-use behaviors in drug-using pregnant patients.
AB  - BACKGROUND: HIV sexual-risk and drug-use behavior predictors have been studied in
      non-pregnant but not pregnant drug-dependent populations. OBJECTIVE: Examine the
      ability of the ASI composite scores to predict HIV sexual- and drug-risk scores
      as well as the individual items of a modified version of the Risk Assessment
      Battery in drug-using pregnant women. METHODS: Pregnant women (N = 76) completing
      pretreatment ASI and HIV-risk questionnaires. RESULTS: The Legal composite score
      was the sole significant predictor of the sexual-risk score, with a 1 SD increase
      in the Legal composite score resulting in a 24% increase in sexual-risk, p <
      .001. The Medical, Drug, and Legal composite scores were each significant
      predictors of the drug-risk score, with a 1 SD increase resulting in a 31%
      decrease, and 121% and 73% increases, respectively, in drug-risk, all ps < .05.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Drug-using pregnant women and their
      fetuses are vulnerable to the consequences of both sexual-risk behaviors and drug
      use. The ASI may help screen such patients for HIV sexual-risk and drug-use
      behaviors as a first step in tailoring treatment to address these issues.

PMID- 20141394
TI  - Psychiatric and substance abuse comorbidity among HIV seropositive and HIV
      seronegative prisoners in Malaysia.
AB  - OBJECTIVE: To examine the association between HIV infection and psychiatric
      disorders among prisoners, where mental illness, substance abuse, and HIV are
      disproportionately represented. DESIGN: Cross-sectional study. METHODS: Using a
      sequential randomization scheme, 200 HIV-seropositive and 200 HIV-seronegative
      prisoners were selected for evaluation of psychiatric illnesses with the
      Structured Clinical Interview for Diagnostic Statistical Manual of Mental
      Disorders-IV (SCID-I). RESULTS: The prevalence of mental illness and substance
      use disorders, particularly opioid dependence, was extremely high. HIV infection
      was significantly correlated with age, ethnicity, marital status, history of
      injection drug use, lifetime duration of incarceration, substance abuse, and
      polysubstance drug use. After controlling for potential confounders, HIV
      infection was significantly associated with non-substance-induced psychiatric
      disorders (AOR = 1.92; 95% CI: 1.03-3.59). While prisoners with a triple
      diagnosis (psychiatric disorders, substance use disorders, and HIV) spent 46.7
      more cumulative lifetime months in prison than those with only a psychiatric
      diagnosis (p < .01), those with a dual diagnosis (psychiatric plus substance use
      disorders) were comparable to those with one psychiatric diagnosis only. Neither
      HIV infection nor triple diagnosis was associated with violent offenses.
      CONCLUSION: These findings suggest that a public health approach that
      simultaneously addresses psychiatric illnesses, substance abuse, and HIV
      infection is needed in both the correctional and the community settings in order
      to provide adequate care for triply-diagnosed patients and prevent them from
      returning to prison.

PMID- 20141395
TI  - Patterns of alcohol consumption and sexual behavior among young adults in
      nightclubs.
AB  - BACKGROUND: Alcohol consumption has been linked to a variety of sexual risk
      behaviors. However, much research addresses this connection among college
      students, ignoring other social contexts in which this association may be
      prevalent, such as club settings. OBJECTIVES: As such, this study assessed
      patterns of drinking and sexual activity among young adults who frequent
      nightclubs. METHODS: Using time-space sampling, we surveyed 308 young adults
      (ages 18-29) in New York City clubs. RESULTS: Participants reported binge
      drinking on 52% of drinking days. Roughly, 62% reported recent sex under the
      influence, and 29% of them reported being less safe in sexual situations as a
      result of their drinking. Men reported more days of drinking and binge drinking
      than women, and were more likely to report recent sex under the influence.
      Younger participants were more likely to report being less safe sexually while
      intoxicated. Recent binge drinking was associated with sex after drinking.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These data suggest the need for targeted
      intervention and prevention efforts at nightclubs.

PMID- 20141396
TI  - The relationship between antidepressant use and smoking cessation in pregnant
      women in treatment for substance abuse.
AB  - BACKGROUND: Bupropion's efficacy for smoking cessation in pregnant women is
      unknown. OBJECTIVES: To determine if substance-dependent women prescribed
      bupropion smoked fewer cigarettes/day than those prescribed
      citalopram/escitalopram or no antidepressant medication. METHODS: Comparison of
      smoking in bupropion (n = 11), citalopram/escitalopram (n = 17), and no
      antidepressant (n = 28) groups. RESULTS AND CONCLUSIONS: Trend for greater
      decrease in smoking for the bupropion vs. citalopram/escitalopram group [-6.4 vs.
      -.4 cigarettes/day (p = .276)], although the bupropion decrease was similar to
      that seen in the no antidepressant group [-5.3 cigarettes/day]. SCIENTIFIC
      SIGNIFICANCE: Data support continued study of bupropion in depressed pregnant
      substance-dependent smokers.

PMID- 20141397
TI  - Personality traits of cocaine-dependent patients associated with cocaine-positive
      baseline urine at hospitalization.
AB  - BACKGROUND: Cocaine abstinence at treatment entry is considered a predictor of
      good response in cocaine dependence treatment. Therefore, identification of
      factors facilitating pretreatment cocaine abstinence could be useful for
      developing new therapeutic strategies. OBJECTIVE: This retrospective chart review
      study examines the association between personality traits and cocaine-positive
      baseline urinalysis (CPB) in cocaine-dependent inpatients. METHODS: All 107
      participants met DSM-IV criteria for cocaine dependence, and were admitted
      consecutively to a closed addiction unit for detoxification treatment.
      Personality was assessed with the Temperament and Character Inventory and the
      Millon Clinical Multiaxial Inventory (MCMI-II). RESULTS: CPB was detected in 80
      patients (74.8%). The logistic regression model solely based on personality
      dimensions showed that only the MCMI-II avoidant traits were significantly
      associated with a decreased probability of cocaine-dependent patients presenting
      CPB. The logistic regression model based on both personality dimensions and
      substance use-related variables alike retained the number of days of cocaine use
      during the last 30 days as a risk factor, and alcohol dependence and the MCMI-II
      schizoid dimension as protective factors in predicting CPB results. CONCLUSION
      AND SCIENTIFIC SIGNIFICANCE: Avoidant and schizoid traits are personality
      dimensions of cocaine-dependent patients that are associated with cocaine
      abstinence prior to inpatient admission. These findings suggest an inverse
      relationship between social isolation and CPB. Notwithstanding, more research is
      needed, not only to assess the generalizability of these findings, but also to
      enrich the personality and substance use model with variables related to
      readiness to change.

PMID- 20141398
TI  - Assessment of a hepatitis educational group for veterans with substance use
      disorders.
AB  - BACKGROUND: In 2005 the substance use disorders (SUD) clinic at the Minneapolis
      Veterans Affairs Medical Center launched the Liver Health Initiative in an effort
      to improve hepatitis education, screening, prevention, and treatment referral
      services for veterans receiving SUD services. One component of the Liver Health
      Initiative is an hour-long educational group; the Healthy Liver Group.
      OBJECTIVES: After the Healthy Liver Group was firmly established, an evaluation
      took place in order to measure: 1) change in patient knowledge, 2) participant
      satisfaction, and 3) attitudes toward hepatitis A and B vaccinations. METHODS:
      From August 2007 to May 2008, 102 veterans filled out a paper survey before and
      after their experience in the Healthy Liver Group. SIGNIFICANCE AND CONCLUSIONS:
      The results of this survey show an increase in basic knowledge of hepatitis, high
      levels of patient satisfaction, and strong acceptance of vaccinations for
      hepatitis A and B. Overall, the survey indicates that the Healthy Liver Group is
      providing an important service and is generally well accepted by patients.

PMID- 20141399
TI  - The relationship between performance on the Shipley Institute of Living Scale
      (SILS) and hepatitis C infection among active injection drug users in Baltimore,
      Maryland.
AB  - BACKGROUND: Hepatitis C represents a significant public health problem,
      particularly among injection drug users. Other than injection drug practices,
      little is understood about individual level characteristics that may place some
      injection drug users at particularly high risk. OBJECTIVES: The current study
      sought to examine two associations among active, regular heroin injection drug
      users. The first was to determine whether there was an association between two
      scales from the Shipley Institute of Living Scale (SILS: a neuropsychological
      measure used to estimate cognitive impairment/intellectual functioning) and self
      reported preexisting conditions independent of years of drug use. The second was
      to examine whether performance on the scales was associated with hepatitis C
      infection. METHODS: Data from 260 HIV negative injection drug users from the
      Baltimore metropolitan region were used. Participants completed a risk behavior
      interview, brief neuropsychological battery, and were tested for Hepatitis C.
      RESULTS: Findings indicated that scale performances varied by self-reported
      learning disabilities and attention deficit disorder. Poorer performance on one
      scale was statistically significantly associated with greater hepatitis C
      prevalence on the vocabulary scale, the discrepancy scale showed a statistical
      trend. CONCLUSIONS: Cognitive impairment measured among this sample of injection
      drug use was related to pre-existing conditions and hepatitis C independent of
      years of drug use. Such impairment may exist prior to initiation of use and
      increase vulnerability to poor health outcomes among injection drug users.
      SCIENTIFIC SIGNIFICANCE: This study highlights the need for interventions
      targeting a possible high risk subpopulation of injection drug users.

PMID- 20141400
TI  - Patients with substance use and personality disorders: a comparison of patient
      characteristics, treatment process, and outcomes in Swiss and U.S. substance use
      disorder programs.
AB  - BACKGROUND: Cross-cultural comparisons may increase our understanding of
      different models of substance use treatment and help identify consistent
      associations between patients' characteristics, treatment conditions, and
      outcomes. OBJECTIVES: The aim of the study was to compare matched samples of
      substance use disorder (SUD) patients with personality disorders (PD) in Swiss
      and the United States (U.S.) residential SUD treatment programs and examine the
      relationship of program characteristics to 1-year outcomes. METHODS: A
      prospective, naturalistic design was used to compare 132 demographically matched
      Swiss and U.S. male patients drawn from a sample of 10 Swiss and 15 U.S. public
      treatment programs. Patients completed comparable inventories at admission,
      discharge, and 1-year follow-up. RESULTS: Compared to Swiss SUD-PD patients, U.S.
      SUD-PD patients had more severe substance use and psychosocial problems at
      admission and follow-up. More intensive treatment and a stronger emphasis on
      patients' involvement were related to better outcomes for both Swiss and U.S. SUD
      PD patients. CONCLUSION: There may be some cross-cultural consistency in the
      associations between treatment characteristics and SUD-PD patients' outcomes.
      SCIENTIFIC SIGNIFICANCE: Treatment evaluation findings from representative
      programs in one country may apply elsewhere and contribute to our overall
      knowledge about how to improve SUD-PD patients' outcomes.

PMID- 20141401
TI  - Prevalence of tobacco use among young adult males in India: a community-based
      epidemiological study.
AB  - BACKGROUND: Prevalence of tobacco use in India is reaching alarming proportions,
      despite efforts by both World Health Organization (WHO) and Government of India
      (GOI) in controlling it. Part of the problem has been lack of available data on
      tobacco use in various groups. Although Global Youth Tobacco Survey (GYTS) and
      National Family Health Survey (NFHS) III have focused on adolescents and adults,
      respectively, data on use among young adults is lacking. Another limitation has
      been the use of the questionnaire method to determine tobacco use which may not
      reveal exact prevalence. This study aimed to explore the prevalence of tobacco
      use among young adult males in Ranchi, as confirmed by serum cotinine levels.
      METHODS: Five-hundred male students were selected through systematic randomized
      process to represent 5 universities in Ranchi. After informed consent, the
      students were administered Tobacco and Other Substance Use questionnaire and then
      subjected to urine Rapid Nicotine Test to improve sensitivity and biologically
      confirm prevalence. All tobacco users then were administered Fagerstrom's Scale
      for Severity of Nicotine Dependence. RESULTS AND CONCLUSION: Biologically
      confirmed prevalence of tobacco use among male students was 55.6%, revealing high
      degree of prevalence in this age group. Predominant form of tobacco use was
      cigarettes (78%) followed by khaini (20%) and gutkha (2%), showing that most
      young adults use cigarettes possibly due to the 'cool image' associated with it.
      Seventy-seven percent of all tobacco users want to quit, thereby giving a strong
      opportunity to carry out cessation services in this group. There was higher mean
      Fagerstrom's Scale for Severity of Nicotine Dependence (FTND) score in smokers
      (6.7 +/- 2.2) compared to chewers (4.6 +/- 2.5), revealing higher severity of
      dependence among smokers than chewers.

PMID- 20141402
TI  - Heavy injection drug use is associated with lower percent body fat in a multi
      ethnic cohort of HIV-positive and HIV-negative drug users from three U.S. cities.
AB  - BACKGROUND: The clinical implications of lower body weight in drug using
      populations are uncertain given that lower mean weights may still fall within the
      healthy range. OBJECTIVES: To determine the effect of type, mode and frequency of
      drug use on underlying body composition after accounting for differences in body
      shape and size. METHODS: We conducted a cross-sectional analysis of 511
      participants from the Tufts Nutrition Collaborative (TNC) Study. Data included
      measures of body composition, a 24-hour dietary recall, and a detailed health
      history and lifestyle questionnaire. Multivariate regression analysis was used to
      determine the independent effect of drug use on percent body fat (BF) after
      adjusting for BMI and waist circumference. RESULTS: Heavy injection drug users
      (IDUs) had a 2.6% lower percent BF than non-users after adjusting for BMI, waist
      circumference, and other confounders. (p = 0.0006). Differences in percent BF
      were predominantly due to higher lean mass, rather than lower fat mass. Cocaine
      and heroin had similar effects on body composition. CONCLUSIONS: In the U.S.,
      where the general population is prone to over-nutrition, the average percent BF
      for heavy injectors does not fall into a range low enough to suggest harmful
      effects. However, in populations with substantial levels of under-nutrition,
      small differences in percent BF among drug users will have a greater impact on
      health status. SCIENTIFIC SIGNIFICANCE: Differences in BMI, weight and body
      composition are not always straightforward. Accounting for underlying nutritional
      status and relative differences in fat and FFM is critical when interpreting
      results. diagnosed patients and prevent them from returning to prison.

PMID- 20141403
TI  - Effects of TGF-beta1 on endothelial factors.
AB  - This study investigated the mechanistic effect of transforming growth factor
      beta1 (TGFbeta1) on the endothelial mediators: endothelin-1 (ET-1), prostacyclin
      (PGI(2)) and nitric oxide (NO) in the endothelial cell line 1G11. Endothelial
      cells were incubated with increasing concentrations of TGFbeta1 in the presence
      and absence of growth medium (deprived) or various inhibitors. In deprived cells,
      TGFbeta1 increased the release of PGI(2) (6-keto-PGF1alpha) concomitantly to an
      increase in COX-2 expression, whereas the production of ET-1 and NO metabolites
      was not affected. Either the removal of prior serum and heparin deprivation or NO
      synthase inhibition by L-NAME unmasked an inhibitory effect of TGFbeta1 on ET-1
      production. Indomethacin abolished the TGFbeta1 inhibitory action on L-NAME
      increased ET-1 production. These results show that TGFbeta1 induces an increase
      in production of PGI(2) that is consecutive to an induction of COX-2 in
      endothelial cells. This increase in PGI(2) partly accounts for the inhibitory
      action of TGFbeta1 on ET-1 secretion.

PMID- 20141405
TI  - Relationship between tactile spatial resolution and digital dexterity during
      childhood.
AB  - The aim of this study was to determine whether tactile spatial resolution and
      digital dexterity performance are associated during childhood. A total of 104
      healthy children (52 boys and 52 girls) were assessed. The tactile spatial
      resolution threshold was determined using an enlarged set of JVP domes with a
      procedure adapted for children. Digital dexterity was tested with the Purdue
      Pegboard Test. While tactile spatial resolution and digital dexterity improved
      with age following a parallel evolution, no correlation was found between the
      scores of the children for both tests. We suggest that central maturational
      processes are responsible for a global refinement of sensory and motor function
      between the ages of 4 and 10 years, reaching the range of adult values at this
      age.

PMID- 20141404
TI  - Elevated blood lactate is associated with increased motor cortex excitability.
AB  - No information has yet been provided about the influence of blood lactate levels
      on the excitability of the cerebral cortex, in particular, of the motor cortex.
      The aim of the present study was to examine the effects of high blood lactate
      levels, induced with a maximal cycling or with an intravenous infusion, on motor
      cortex excitability. The study was carried out on 17 male athletes; all the
      subjects performed a maximal cycling test on a mechanically braked
      cycloergometer, whereas 6 of them were submitted to the intravenous infusion of a
      lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, at the
      end, as well as 5 and 10 min after the conclusion, venous blood lactate was
      measured and excitability of the motor cortex was evaluated by using the
      transcranial magnetic stimulation. In both of these experimental conditions, it
      was observed that an increase of blood lactate is associated with a decrease of
      motor threshold, that is, an enhancement of motor cortex excitability. We
      conclude by hypothesizing that in the motor cortex the lactate could have a
      protective role against fatigue.

PMID- 20141406
TI  - Graded cutaneous electrical vs thermal stimulation in humans shows different
      insular and cingulate cortex activation.
AB  - Pain can result from various sensory input modalities. To elucidate the
      differences of cortical responses to graded electrical and thermal stimulation,
      functional magnetic resonance imaging (fMRI) results of two studies using the
      same stimulation paradigms but different modalities with 15 healthy subjects each
      are compared. During painful electrical stimulation contralateral dorsal
      posterior insula and ventral posterior anterior cingulate cortex (ACC) activated
      more. During thermal stimulation, there was more activation in ipsilateral
      primary motor area (MI)/primary sensory area (SI) complex and premotor areas as
      well as dorsal posterior ACC. Thus electrostimulation preferably activates
      structures of the lateral pain projection system resulting in contralateral
      dorsal posterior insula and ventral posterior ACC activation. During thermal
      stimulation, more dorsal areas of the posterior ACC activated. The activation of
      ipsilateral MI/SI complex and premotor areas may be attributed to the slower
      perception of thermal stimuli and resulting re-evaluation. This has to be taken
      into account in the interpretation of other cross-modality studies as well.

PMID- 20141407
TI  - The effect of immobilization of the head and trunk on arm-cycling-induced
      depression of soleus motoneuron pool excitability.
AB  - The purpose of this study was to investigate the effects of immobilization of the
      head and trunk on arm-cycling-induced depression of leg motoneuron pool
      excitability. Seven healthy humans participated in this study. The subjects sat
      on a chair with or without immobilization of the head and trunk. The subjects
      rhythmically cycled a crank of the ergometer with their hands at a frequency of 1
      Hz. Soleus H-reflexes were evoked during arm cycling and during stational arm
      position. The H-reflexes were not significantly depressed during arm cycling when
      the head and trunk were immobilized, but were significantly depressed during arm
      cycling when the head and trunk were not immobilized. The H-reflex depression
      during arm cycling in the non-immobilized condition was significantly larger than
      that in the immobilized condition. These findings support our hypothesis that the
      depression of leg motoneuron pool excitability induced by arm cycling is
      partially related to postural activity in the head and trunk.

PMID- 20141408
TI  - Organization and morphology of thalamocortical neurons of mouse ventral lateral
      thalamus.
AB  - The ventral lateral nucleus of the thalamus (VL) serves as a central integrative
      center for motor control, receiving inputs from the cerebellum, striatum, and
      cortex and projecting to the primary motor cortex. We aimed to determine the
      somatotopy and morphological features of the thalamocortical neurons within mouse
      VL. Retrograde tracing studies revealed that whisker-related VL neurons were
      found relatively anterior and medial to those labeled following injection of
      retrograde tracer into hindpaw motor areas. Simultaneous injections of
      fluorescent microspheres in both cortical regions did not result in double
      labeled neurons in VL. Quantitative analysis of dendritic and somatic
      morphologies did not reveal any differences between hindpaw and whisker
      thalamocortical neurons within VL. The morphology of the thalamocortical neurons
      within mouse VL is similar to those in other mammals and suggests that mouse can
      be used as a model system for studying thalamocortical transformations within the
      motor system as well as plasticity following sensory deprivation or enrichment.

PMID- 20141409
TI  - More diversity and more convergence in tunicate biology.
AB  - The 5th International Tunicate Meeting (ITM5) was held at the Okinawa Industry
      Support Center (Naha, Okinawa, Japan) from June 21 to 25, 2009, with support from
      the Okinawa Institute of Science and Technology (OIST) and the Inoue Foundation
      for Science. Tunicates are defined as deuterostome metazoans that have notochord
      in the tail at one point or at all times during their life. Presence of a
      cellulosic integument is also a synapomorphy for this taxon, which consists of
      three classes: Ascidiacea, Thaliacea, and Appendicularia. Ascidians, the largest
      class, are always sessile, while thaliaceans and appendicularians are pelagic
      throughout their life. Many unique and interesting data sets are available that
      facilitate research on tunicates, such as full-genome information for Ciona,
      numerous ESTs with in-situ hybridization images, well-documented cell lineages
      during embryogenesis, among many others. The present note gives an overview of
      the topics from the sessions and plenary lectures of ITM5. As seen below, the
      tunicate scientific community is worldwide, with flexible networks among tunicate
      biologists, and a particularly wide range of species diversity and phenomena were
      presented during ITM5. ITM6 is planned for 2011 in Montreal.

PMID- 20141410
TI  - Identification of genes downstream of nodal in the Ciona intestinalis embryo.
AB  - Nodal, a growth factor belonging to the TGF-beta superfamily, is required for the
      formation of the neural tube in Ciona intestinalis. Previous studies have
      revealed many genes whose expression is controlled by Nodal in the Ciona embryo;
      however, all of them encode transcription factors and signaling molecules. In the
      present study, we identified five genes upregulated or downregulated by the
      overexpression of Nodal in embryos of C. intestinalis. The upregulated genes
      included those encoding type IV collagen 1/3/5, laminin-alpha5, and Prickle. The
      downregulated genes included those encoding glypican and delta1-protocadherln
      like. Many of these genes were expressed in the neural plate at the late gastrula
      stage. The present study revealed candidate effector genes that directly
      regulate, in response to Nodal, the morphogenesis of the neural tube in Ciona
      intestinalis.

PMID- 20141411
TI  - Upstream regulatory sequences required for specific gene expression in the
      ascidian neural tube.
AB  - The relatively simple structure of ascidians and the number of associated
      molecular resources that are available make ascidians an excellent experimental
      system for Investigating the molecular mechanisms underlying neural tube
      formation. The ascidian neural tube demonstrates the same basic morphology as
      that of vertebrates. We have described the expression of the neural tubespecific
      gene CiNut1, which is expressed within neural tube precursor cells from the
      gastrula stage, and along the entire length of the neural tube during its
      formation. In this study, we focused on the transcriptional mechanisms that
      regulate CiNut1 expression. We found that an approximately 1.0 kb upstream
      sequence was able to recapitulate endogenous CiNut1 expression. A deletion
      analysis showed that the 119 bp upstream fragment containing two ZicL-binding
      consensus sequences and one Fox core sequence could also drive the neural tube
      specific expression. When mutations were Introduced into the distal ZicL binding
      site (ZicL1), the neural tube-specific expression almost disappeared. Although
      the Importance of the proximal ZicL site (ZicL2) and the Fox core sequence have
      yet to be elucidated, we hypothesize that ZicL regulates gene transcription in
      the entire neural tube of the ascidian.

PMID- 20141412
TI  - Distinctive expression patterns of Hedgehog pathway genes in the Ciona
      intestinalis larva: implications for a role of Hedgehog signaling in
      postembryonic development and chordate evolution.
AB  - Members of the Hedgehog (Hh) family are soluble ligands that orchestrate a wide
      spectrum of developmental processes ranging from left-right axis determination of
      the embryo to tissue patterning and organogenesis. Tunicates, including
      ascidians, are the closest relatives of vertebrates, and elucidation of Hh
      signaling in ascidians should provide an important clue towards better
      understanding the role of this pathway in development. In previous studies,
      expression patterns of genes encoding Hh and its downstream factor Gli have been
      examined up to the tailbud stage in the ascidian embryo, but their expression in
      the larva has not been reported. Here we show the spatial expression patterns of
      hedgehog (Ci-hh1, Ci-hh2), patched (Ci-ptc), smoothened (Ci-smo), and Gli (Ci
      Gli) orthologs in larvae of the ascidian Ciona intestinalis. The expression
      patterns of Ci-hh2 and Ci-Gli dramatically change during the period between the
      late tailbud embryo and the swimming larva. At the larval stage, expression of Ci
      Gli was found in a central part of the endoderm and in the visceral ganglion,
      while Ci-hh2 was expressed in two discrete endodermal regions, anteriorly and
      posteriorly adjacent to the cells expressing Gli. The expression patterns of
      these genes suggest that the Hh ligand controls postembryonic development of the
      endoderm and the central nervous system. Expression of a gene encoding Hh in the
      anterior and/or pharyngeal endoderm is probably an ancient chordate character;
      diversification of regulation and targets of the Hh signaling in this region may
      have played a major role in the evolution of chordate body structures.

PMID- 20141413
TI  - Regeneration in the hemichordate Ptychodera flava.
AB  - When the body of P. flava is severed, the animal has the ability to regenerate
      its missing anterior or posterior as appropriate. We have focused on anterior
      regeneration when the head and branchial regions are severed from the body of the
      worm. After transection, the body wall contracts and heals closed in 2 to 3 days.
      By the third day a small blastema is evident at the point of closure. The
      blastema grows rapidly and begins the process of differentiating into a head with
      a proboscis and collar. At 5 days the blastema has increased greatly in size and
      differentiated into a central bulb, the forming proboscis, and two lateral
      crescents, the forming collar. Between 5 and 7 days a mouth opens ventral to the
      differentiating blastema. Over the next few days the lateral crescents extend to
      encircle the proboscis and mouth, making a fully formed collar. By 10 to 12 days
      a new head, sized to fit the worm's body, has grown attached to the severed site.
      At about this time the animal regains apparently normal burrowing behavior. After
      the head is formed, a second blastema-like area appears between the new head and
      the old body and a new branchial region is inserted by regeneration from this
      blastema over the next 2 to 3 weeks. The regenerating tissues are unpigmented and
      whitish such that in-situ hybridization can be used to study the expression of
      genes during the formation of new tissues.

PMID- 20141414
TI  - Natural apoptosis during the blastogenetic cycle of the colonial ascidian
      Botryllus schlosseri: a morphological analysis.
AB  - Colonies of the compound ascidian Botryllus schiosseri undergo regular generation
      changes, during which adult zooids are progressively resorbed and replaced by
      growing buds. The generation change, or take-over, is characterized by massive
      cell death by apoptosis, as indicated by nuclear condensation, activation of
      caspases, overexpression of molecules recognized by antibodies against mammalian
      Bax, Fas, and FasL, changes in the expression of surface molecules by senescent
      cells of zooid tissues, and recruitment of circulating phagocytes in zooid
      tissues which ensure the complete clearing of dying cells. The entire process
      lasts 24-36 h at 20 degrees C and has been subdivided, on the basis of the degree
      of contraction of old zooids, into four substages. In the present work, we
      carried out a detailed morphological analysis of the events occurring in zooid
      tissues during the take-over substages. Results Indicate that traces of apoptosis
      can be found in the epidermis, peribranchial epithelium, and heart in the late
      substage but are easily found in the branchial basket 2-4 h after the beginning
      of the generation change, thus confirming the antero-posterior progression of
      cell death, at least in the alimentary system.

PMID- 20141415
TI  - Differential regional expression of genes in the developing brain of Ciona
      intestinalis embryos.
AB  - Our previous transcriptome analysis identified 565 genes that are preferentially
      expressed in the developing brain of Ciona intestinalis larvae. Here, we show by
      in-situ hybridization that the spatial expression patterns of these brain
      specific genes fall into different categories depending on the regions where the
      gene is expressed. For example, Ci-opsin3 and Ci-Dkk3 are expressed in the entire
      brain, Ci-tyrosinase and Ci-TYRP1 in the dorsal region, and Ci-synaptotagmin3, Ci
      ZF399, and Ci-PTFb in the ventral region. Other genes are specific to the
      posterior, anterior, central, posterior and ventral, or anterior-ventral region
      of the brain. This regional expression of genes in the Ciona brain is not always
      associated with cell lineage, suggesting that complex mechanisms control the
      regionalized expression of brain-specific genes.

PMID- 20141416
TI  - Regulation of notochord-specific expression of Ci-Bra downstream genes in Ciona
      intestinalis embryos.
AB  - Brachyury, a T-box transcription factor, is expressed in ascidian embryos
      exclusively in primordial notochord cells and plays a pivotal role in
      differentiation of notochord cells. Previously, we identified approximately 450
      genes downstream of Ciona intestinalis Brachyury (Ci-Bra), and characterized the
      expression profiles of 45 of these in differentiating notochord cells. In this
      study, we looked for cisregulatory sequences in minimal enhancers of 20 Ci-Bra
      downstream genes by electroporating region within approximately 3 kb upstream of
      each gene fused with lacZ. Eight of the 20 reporters were expressed in notochord
      cells. The minimal enchancer for each of these eight genes was narrowed to a
      region approximately 0.5-1.0-kb long. We also explored the genome-wide and
      coordinate regulation of 43 Ci-Bra-downstream genes. When we determined their
      chromosomal localization, it became evident that they are not clustered in a
      given region of the genome, but rather distributed evenly over 13 of the 14 pairs
      of chromosomes, suggesting that gene clustering does not contribute to coordinate
      control of the Ci-Bra downstream gene expression. Our results might provide
      Insights Into the molecular mechanisms underlying notochord formation in
      chordates.

PMID- 20141417
TI  - Origin and genetic evolution of the vertebrate skeleton.
AB  - The current understanding of the origin and evolution of the genetic cassette for
      the vertebrate skeletal system is reviewed. Molecular phylogenetic analyses of
      fibrillar collagen genes, which encode the main component of both cartilage and
      mineralized bone, suggest that genome duplications in vertebrate ancestors were
      essential for producing distinct collagen fibers for cartilage and mineralized
      bone. Several data Indicate co-expression of the ancestral copy of fibrillar
      collagen with the SoxE and Runx transcription factors. Therefore, the genetic
      cassette may have already existed in protochordate ancestors, and may operate in
      the development of the pharyngeal gill skeleton. Accompanied by genome
      duplications in vertebrate ancestors, this genetic cassette may have also been
      duplicated and co-opted for cartilage and bone. Subsequently, the genetic
      cassette for cartilage recruited novel genetic material via domain shuffling.
      Aggrecan, acquired by means of domain shuffling, performs an essential role in
      cartilage as a shock absorber. In contrast, the cassette for bone recruited new
      genetic material produced by tandem duplication of the SPARC/osteonectin genes.
      Some of the duplicated copies of SPARC/osteonectin became secretory Cabinding
      phosphoproteins (SCPPs) performing a central role in mineralization by regulating
      the calcium phosphate concentration. Comparative genome analysis revealed similar
      molecular evolutionary histories for the genetic cassettes for cartilage and
      bone, namely duplication of the ancestral genetic cassette and recruitment of
      novel genetic material.

PMID- 20141418
TI  - Oikopleura dioica alcohol dehydrogenase class 3 provides new insights into the
      evolution of retinoic acid synthesis in chordates.
AB  - Enzymes that synthesize retinoic acid (RA) constitute the first level of
      regulation of RA action. In vertebrates, enzymes of the medium-chain alcohol
      dehydrogenase (MDR-Adh) family catalyze the first step of the RA synthetic
      pathway by oxidizing retinol. Among MDR-Adh enzymes, Adh3 is the only member
      present in non-vertebrates, and whether Adh3 is actually involved in RA
      biosynthesis remains uncertain. Here, we investigate the MDR-Adh family in
      Oikopleura dioica, a urochordate representing the sister group to vertebrates.
      Oikopleura is of special interest because it has lost the classical RA role in
      development, which relaxed evolutionary constraints to preserve the RA-genetic
      machinery, leading to the loss of RA-system components. The hypothesis that Adh3
      plays a role in RA synthesis predicts that the relaxation of selection in
      Oikopleura should have led to the loss of Adh3, or changes in residues related to
      retinol oxidation. The hypothesis also predicts changes in the expression pattern
      of Oikopleura Adh3 compared to other chordates that preserved RA-signaling. Our
      results, however, revealed the presence of a highly conserved Adh3 gene in
      Oikopleura, with no significant changes in functional residues. Our results also
      revealed that the Oikopleura Adh3 expression remains unchanged in comparison to
      other non-vertebrate chordates, restricted to specific compartments of the
      digestive system. Because Adh3 has been highly conserved in an animal that has
      dismantled the RA system, we conclude that Adh3 preservation is not due to a
      conserved role in RA synthesis. Thereby, if Adh3 plays a role in RA synthesis in
      vertebrates, it might be a lineage-specific neofunctionalization.

PMID- 20141419
TI  - Neuropeptides, hormone peptides, and their receptors in Ciona intestinalis: an
      update.
AB  - The critical phylogenetic position of ascidians leads to the presumption that
      neuropeptides and hormones in vertebrates are highly likely to be evolutionarily
      conserved in ascidians, and the cosmopolitan species Ciona intestinalis is
      expected to be an excellent deuterostome Invertebrate model for studies on
      neuropeptides and hormones. Nevertheless, molecular and functional
      characterization of Ciona neuropeptides and hormone peptides was restricted to a
      few peptides such as a cholecystokinin (CCK)/gastrin peptide, cionin, and
      gonadotropin-releasing hormones (GnRHs). In the past few years, mass
      spectrometric analyses and database searches have detected Ciona orthologs or
      prototypes of vertebrate peptides and their receptors, including tachykinin,
      insulin/relaxin, calcitonin, and vasopressin. Furthermore, studies have shown
      that several Ciona peptides, including vasopressin and a novel GnRH-related
      peptide, have acquired ascidian-specific molecular forms and/or biological
      functions. These findings provided indisputable evidence that ascidians, unlike
      other invertebrates (including the traditional protostome model animals), possess
      neuropeptides and hormone peptides structurally and functionally related to
      vertebrate counterparts, and that several peptides have uniquely diverged in
      ascidian evolutionary lineages. Moreover, recent functional analyses of Ciona
      tachykinin in the ovary substantiated the novel tachykininergic protease
      assoclated oocyte growth pathway, which could not have been revealed in studies
      on vertebrates. These findings confirm the outstanding advantages of ascidians in
      understanding the neuroscience, endocrinology, and evolution of vertebrate
      neuropeptides and hormone peptides. This article provides an overview of basic
      findings and reviews new knowledge on ascidian neuropeptides and hormone
      peptides.

PMID- 20141420
TI  - Comparative overview of toll-like receptors in lower animals.
AB  - Toll-like receptors (TLRs) have been shown to play a crucial role in host defense
      against pathogenic microbes in innate immunity in mammals. Recent genome-wide
      analyses have suggested that TLRs or related genes are conserved in the genome of
      non-mammalian organisms such as fishes, cyclostomes, ascidians, cephalochordates,
      sea urchins, and hydras. However, neither active forms nor functions of authentic
      invertebrate TLRs had been elucidated. Quite recently, we verified the
      structures, localization, ligand recognition, activities, and inflammatory
      cytokine production of two TLRs in the ascidian Ciona intestinalis, designated Ci
      TLR1 and Ci-TLR2. Both Ci-TLRs possess a unique structural organization, with
      moderate sequence similarity to functionally characterized vertebrate TLRs, and
      are expressed predominantly in the stomach and intestine as well as in hemocytes.
      Unlike vertebrate TLRs, Ci-TLR1 and Ci-TLR2 are present in both the plasma
      membrane and endosomes. Furthermore, both Ci-TLR1 and Ci-TLR2 stimulate NF-kappaB
      induction in response to multiple pathogenic ligands that are differentially
      recognized by respective vertebrate TLRs. Pathogenic ligands that stimulate the
      Ci-TLRs also induce the expression of Ci-TNFalpha in the intestine and stomach,
      where the Ci-TLRs are abundantly expressed. These data reveal the conservation of
      the TLR-triggered innate immune system in C. intestinalis, and both common and
      unique biological and immunological functions of the Ci-TLRs. Based on the latest
      findings, we review recent advances in studies of TLRs or related receptors in
      fish, cyclostomes, deuterostome invertebrates, and hydra, and also the
      significance of studies of lower organism TLRs.

PMID- 20141421
TI  - Computational identification of Ciona intestinalis microRNAs.
AB  - MicroRNAs (miRNAs) are conserved non-coding small RNAs with potent post
      transcriptional gene regulatory functions. Recent computational approaches and
      sequencing of small RNAs had indicated the existence of about 80 Ciona
      intestinalis miRNAs, although it was not clear whether other miRNA genes were
      present in the genome. We undertook an alternative computational approach to look
      for Ciona miRNAs. Conserved non-coding sequences from the C. intestinalis genome
      were extracted and computationally folded to identify putative hairpin-like
      structures. After applying additional criteria, we obtained 458 miRNA candidates
      whose sequences were used to design a custom microarray. Over 100 of our
      predicted hairpins were identified in this array when probed with RNA from
      various Ciona stages. We also compared our predictions to recently deposited
      sequences of Ciona small RNAs and report that 170 of our predicted hairpins are
      represented in this data set. Altogether, about 250 of our 458 predicted miRNAs
      were represented in either our array data or the small-RNA sequence database.
      These results suggest that Ciona has a large number of genomically encoded miRNAs
      that play an important role in modulating gene activity in developing embryos and
      adults.

PMID- 20141422
TI  - SL RNA genes of the ascidian tunicates Ciona intestinalis and Ciona savignyi.
AB  - We characterized by bioinformatics the trans-spliced leader donor RNA (SL RNA)
      genes of two ascidians, Ciona intestinalis and Ciona savignyi. The Ciona
      intestinalis genome contains approximately 670 copies of the SL RNA gene,
      principally on a 264-bp tandemly repeated element. Fluorescent in-situ
      hybridization mapped most of the repeats to a single site on the short arm of
      chromosome 8. The Ciona intestinalis genome also contains approximately 100
      copies of a >3.6-kb element that carries 1) an SL RNA-related sequence (possible
      a pseudogene) and 2) genes for the U6 snRNA and a histone-like protein. The Ciona
      savignyi genome contains two SL RNA gene classes having the same SL sequence as
      Ciona intestinalis but differing in the intron-like segments. These reside in
      similar but distinct repeat units of 575 bp ( approximately 410 copies) and 552
      bp ( approximately 250 copies) that are arranged as separate tandem repeats. In
      neither Ciona species is the 5S RNA gene present within the SL RNA gene repeat
      unit. Although the number of SL RNA genes is similar, there is little sequence
      similarity between the intestinalis and savignyi repeat units, apart from the
      region encoding the SL RNA itself. This suggests that cis-regulatory elements
      involved in transcription and 3'-end processing are likely to be present within
      the transcribed region. The genomes of both Ciona species also include > 100
      dispersed short elements containing the 16-nt SL sequence and up to 6 additional
      nucleotides of the SL RNA sequence.

PMID- 20141423
TI  - Simple motor system of the ascidian larva: neuronal complex comprising putative
      cholinergic and GABAergic/glycinergic neurons.
AB  - The ascidian larva is an excellent model for studies of the functional
      organization and neuronal circuits of chordates due to its remarkably simple
      central nervous system (CNS), comprised of about 100 neurons. To date, however,
      the identities of the various neurons in the ascidian larva, particularly their
      neurotransmitter phenotypes, are not well established. Acetylcholine, GABA, and
      glycine are critical neurotransmitters for locomotion in many animals. We
      visualized putative cholinergic neurons and GABAergic/glycinergic neurons in the
      ascidian larva by immunofluorescent staining using antibodies against vesicular
      acetylcholine transporter (VACHT) and vesicular GABA/glycine transporter (VGAT),
      respectively. Neurons expressing a cholinergic phenotype were found in the brain
      vesicle and the visceral ganglion. Five pairs of VACHT-positive neurons were
      located in the visceral ganglion. These putative cholinergic neurons extended
      their axons posteriorly and formed nerve terminals proximal to the most anterior
      muscle cells in the tail. VGAT-positive neurons were located in the brain
      vesicle, the visceral ganglion, and the anterior nerve cord. Two distinct pairs
      of VGAT-positive neurons, bilaterally aligned along the anterior nerve cord,
      extended axons anteriorly, near to the axons of the contralateral VACHT-positive
      neurons. Cell bodies of the VGAT-positive neurons lay on these nerve tracts. The
      neuronal complex, comprising motor neurons with a cholinergic phenotype and some
      of the GABA/glycinergic interneurons, has structural features that are compatible
      with a central pattern generator (CPG) producing a rhythmic movement of the tail.
      The simple CPG of the ascidian larva may represent the ancestral state of the
      vertebrate motor system.

PMID- 20141424
TI  - Neural map of the larval central nervous system in the ascidian Ciona
      intestinalis.
AB  - We examined the distribution patterns and axonal pathways of cholinergic,
      GABAergic, and dopaminergic neurons in the central nervous system of Ciona
      intestinalis larvae, based on the expression patterns of two reporter genes (GFP
      and LacZ) driven by the promoters of several neuron-specific genes (vesicular
      acetylcholine transporter, glutamic acid decarboxylase, tyrosine 3-hydroxylase
      and dopa decarboxylase). Putative cholinergic and GABAergic cells were found in
      the sensory vesicle (SV) and visceral ganglion (VG), while putative dopaminergic
      cells were found only in the SV. The axons of almost all putative cholinergic and
      GABAergic cells in the SV extend posteriorly towards the VG and seem to connect
      with motor neurons. Some cells extend axons to the proximal region of the tail
      beyond the trunk-tail boundary. As this tail region contains several neurons,
      these cells may modulate larval behavior through the latter neurons. We also
      found that some putative cholinergic and GABAergic cells in the dorsal VG form a
      complex and extend axons anteriorly to the SV, posteriorly to the tail, and
      possibly ventrally to some motor neurons. Finally, we observed that one pair of
      the anterior most putative cholinergic cells in the ventral VG extends axons
      contralaterally to the right and left caudal axon tracts. We discuss the
      similarity of these cells to the Mauthner cells in vertebrates.

PMID- 20141425
TI  - Intentional overdose with cardiac arrest treated with intravenous fat emulsion
      and high-dose insulin.
AB  - INTRODUCTION: Nebivolol, a beta blocker with 3-10 times more beta1
      cardioselectivity than metoprolol, has caused hypotension and bradycardia in
      overdose. We report a nebivolol-induced cardiac arrest in the setting of a
      polydrug ingestion, successfully resuscitated with intravenous fat emulsion (IFE)
      and high-dose insulin (HDI). CASE REPORT: A 48-year-old man was brought to the
      emergency department after ingesting nebivolol and ethanol, along with possibly
      diazepam and cocaine. He had a heart rate of 71/min and a blood pressure of 98/61
      mmHg. The initial ECG showed sinus rhythm with a QTc of 483 ms and a QRS of 112
      ms. Over the subsequent 4 h, he became bradycardic and hypotensive and developed
      bradyasystolic cardiac arrest. Standard resuscitation including epinephrine had
      no effect. Spontaneous circulation returned 30 s after a 100 mL bolus of 20% IFE,
      and the patient then became briefly hypertensive and tachycardic with heart rate
      and blood pressure measured as high as 123/min and 251/162 mmHg, respectively.
      His care included IFE infusion along with HDI bolus and infusion with doses as
      high as 21.8 units/kg/h. With subsequent hypotension, vasopressors were withheld
      in favor of HDI and supportive care. He was discharged with baseline neurologic
      function. DISCUSSION: We hypothesize that after the administration of IFE the
      epinephrine was able to exert its effect on receptors previously occupied with
      the nebivolol. This would be congruent with the lipid sink theory of IFE
      mechanism. CONCLUSION: We report an overdose involving nebivolol in a polydrug
      ingestion resulting in cardiac arrest, successfully treated with IFE and a very
      HDI infusion.

PMID- 20141426
TI  - Superwarfarin poisoning as a cause of intestinal obstruction.
AB  - A 17-year-old boy was brought to our department with nausea, vomiting, absence of
      flatus or bowel movements, abdominal distension, and pain for about 5 days.
      Emergency abdominal CT scan showed extensive gas-fluid levels in the intestinal
      tract and intestinal wall swelling that indicated acute intestinal obstruction.
      Routine coagulation tests revealed abnormality and further provided evidence of
      superwarfarin poisoning. With high dosage of vitamin K1 and fresh frozen plasma
      therapy, surgery was avoided.

PMID- 20141427
TI  - Antisense oligonucleotide against miR-21 inhibits migration and induces apoptosis
      in leukemic K562 cells.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that are widely involved in
      cancer-related processes. The microRNA-21 (miR-21) has been identified as the
      only miRNA overexpressed in a variety of cancers, including leukemia. However,
      the function of miR-21 is yet unknown in chronic myelogenous leukemia (CML).
      Antisense oligonucleotides (ASOs), as inhibitors of miRNAs, have already been
      applied to therapeutic development and functional identification in miRNA
      research. In this study, we found that the antisense inhibition of miR-21 in K562
      cells suppressed cell migration, promoted cell apoptosis, and inhibited cell
      growth, and up-regulated the expression of the tumor suppressor gene PDCD4.
      Meanwhile, pre-miRNA-21 increased migration and decreased cell apoptosis without
      affecting proliferation. We also validated that PDCD4 is a functional target of
      miR-21 in K562 cells. These effects of miR-21 might be partially due to its
      regulation of PDCD4. Our data suggest that miR-21 may play an oncogenic role in
      the cellular processes of CML, and antisense inhibition of miR-21 may therefore
      be useful as CML therapy.

PMID- 20141428
TI  - The role of B cell depleting therapy in graft versus host disease after
      allogeneic hematopoietic cell transplant.
AB  - Graft versus host disease (GVHD) remains a common complication following
      allogeneic hematopoietic cell transplant (HCT). Historically, research into
      prevention and treatment of GVHD has centered on donor T lymphocytes using
      strategies to suppress or deplete these cells. The role of B lymphocytes in the
      pathogenesis of this disease was brought to prominence following a case report of
      a patient with chronic GVHD who responded to B cell depletion therapy with
      rituximab. Since this original observation, several clinical trials and case
      series have been published on the use of B cell depletion using rituximab in the
      treatment of chronic GVHD. Corresponding to this clinical experience,
      considerable laboratory evidence has revealed the complex interactions between B
      and T cells which culminate in acute and chronic GVHD. More recently, researchers
      have examined the link between B cell immune reconstitution following HCT and the
      development of chronic GVHD. The focus of the next decade will likely be on
      prevention and treatment of GVHD through targeted therapies directed at key
      pathways in this process. This article provides an overview of the current
      understanding regarding the role of B cells in GVHD along with discussion on how
      this knowledge will be used to direct future therapies.

PMID- 20141430
TI  - Co-expression of HoxA9 and bcr-abl genes in chronic myeloid leukemia.
AB  - We have analyzed the co-expression of the bcr-abl and HoxA9 genes in the follow
      up of patients with chronic myeloid leukemia (CML). In the present work we
      measured the HoxA9 and bcr-abl gene expression in sequential samples. In all
      patients, bcr-abl and HoxA9 were expressed at detectable levels in every sample.
      When the results were expressed in relation to abl, two different situations were
      found: (a) patients clinically stable at second sampling, with low relative risk
      at diagnosis (low Sokal's score), did not show significant differences in both
      bcr-abl and HoxA9 levels in the sequential samples analyzed, and (b) patients
      with poor prognosis (showing intermediate or high Sokal's score at diagnosis) had
      increased expression of bcr-abl as well as HoxA9 genes (p < 0.05). Since HoxA9
      gene expression remains at relatively constant levels throughout adult life, our
      results could reflect actual changes in the expression rate of this gene
      associated with bcr-abl during the progression of CML.

PMID- 20141429
TI  - OCT-2 expression and OCT-2/BOB.1 co-expression predict prognosis in patients with
      newly diagnosed acute myeloid leukemia.
AB  - OCT-2 and its co-activator, BOB.1, are B-cell associated transcription factors
      expressed in a subset of patients with acute myeloid leukemia (AML). We evaluated
      OCT-2 and BOB.1 expression by immunohistochemistry in patients with newly
      diagnosed AML. The median overall survival (OS) for patients with varying levels
      of OCT-2 expression was statistically different (p = 0.03) (OCT-2 <10%: 21.7
      months; OCT-2 10-50%: 18.4 months; OCT-2 >50%: 11.6 months). On multivariate
      analysis, co-expression of OCT-2/BOB.1 remained predictive for achievement of
      complete remission (HR 0.44, p = 0.010) and increased risk of relapse (HR 2.30, p
      = 0.047). OCT-2 (per 10% increase) was associated with a decreased progression
      free survival (HR 1.10, p = 0.036) and a trend toward a worse OS (HR 1.10, p =
      0.063). OCT-2 may act as a cell survival factor in AML by mediating expression of
      downstream targets, such as BCL-2. These results will need to be validated
      prospectively.

PMID- 20141431
TI  - Expression of natural killer receptors in T- and NK-cells: comparison of healthy
      individuals, patients with prior stem cell transplant, and patients undergoing
      chemotherapy.
AB  - We studied the expression of natural killer receptors (NKRs) on peripheral blood
      cytotoxic T lymphocytes and NK cells in patients who underwent an allogeneic stem
      cell transplant (SCT), and compared these findings with results from healthy
      individuals (CTRL) and patients undergoing chemotherapy (CHEMO), respectively.
      Peripheral blood mononuclear cells were analyzed by flow cytometry with
      antibodies against the NKRs CD158a, CD158b, CD158e (known as killer
      immunoglobulin-like receptors, KIRs), and CD94. Expression of NKRs was evaluated
      separately in CD56+, CD57+, and CD56/CD57 (double +) subsets of T and NK cells.
      We found mainly differences in CD158a and CD94 expression between the three
      cohorts, with the SCT and CHEMO groups usually showing similar changes, when
      compared to the CTRL population. None of the patients with SCT or CHEMO
      demonstrated patterns of restricted NKR expression. Our results provide a
      comprehensive overview of KIR and CD94 expression in T and NK cells following SCT
      and chemotherapy.

PMID- 20141432
TI  - The antidepressants maprotiline and fluoxetine have potent selective
      antiproliferative effects against Burkitt lymphoma independently of the
      norepinephrine and serotonin transporters.
AB  - The discovery that some selective serotonin transporter- (SSRI) and
      norepinephrine transporter- (NSRI) targeting antidepressants have the potential
      to act as anticancer agents adds greatly to their diverse pharmacological
      application. We report that the SSRI fluoxetine and the NSRI maprotiline are
      potent antiproliferative agents against human Burkitt lymphoma (BL), having
      little effect on normal blood cells. The results of this study show that although
      there is low-level expression of the norepinephrine transporter (NET) in some BL
      cells, NET is not involved in fluoxetine- or maprotiline-mediated cell death, as
      neither norepinephrine nor other NET inhibitors prevented this death. Of other
      NET ligands investigated for activity, only desipramine was found to have a
      similar effect to maprotiline and fluoxetine, suggesting the existence of a
      common selective structural modality for cell death and aiding in the future
      development of more potent analogs. In this study, we also show evidence to
      support previous reports that the serotonin transporter (SERT) has no involvement
      in antidepressant-mediated cell death, as SERT-specific ligands were unable to
      prevent fluoxetine or maprotiline cell death and not all SERT ligands could
      induce cell death. Although no target has yet been identified for the action of
      these compounds, the cell death elicited is potent, selective, and worthy of
      future investigation.

PMID- 20141434
TI  - Targeted therapy in KITD816V-positive mastocytosis: waiting for proof-of
      principle.

PMID- 20141433
TI  - Incidence and survival of lymphohematopoietic neoplasms according to the World
      Health Organization classification: a population-based study from the Victorian
      Cancer Registry in Australia.
AB  - We studied the incidence and relative survival of 39 837 cases of
      lymphohematopoietic neoplasms (LHN) reported to the Victorian Cancer Registry
      during 1982-2004, classified according to the World Health Organization (WHO)
      classification. We modeled excess mortality using Poisson regression to estimate
      differences in survival by age, sex, and time period. Age-standardized incidence
      rates varied across subtypes of lymphoid and myeloid neoplasms. All major
      subtypes predominantly affected the elderly except Hodgkin lymphoma (incidence
      peaks at 20-24 and 75-79 years) and acute lymphoblastic leukemia (0-9 years).
      After an initial rise, overall lymphoid and myeloid incidence stabilized in the
      mid-1990s. The 5-year relative survival was 58% for lymphoid and 35% for myeloid
      neoplasms. Survival improved during 1990-2004 for diffuse large B-cell lymphoma,
      follicular lymphoma, acute myeloid leukemia, chronic myeloid leukemia, and
      myelodysplastic syndromes (p  < 0.001) and declined with advancing age for all
      subtypes (p <  0.001). Female sex was associated with higher survival for most
      myeloid subtypes. The results represent a rare epidemiological characterization
      of the whole range of LHN according to WHO subtypes.

PMID- 20141435
TI  - Relationship of the reduced folate carrier gene polymorphism G80A to methotrexate
      plasma concentration, toxicity, and disease outcome in childhood acute
      lymphoblastic leukemia.

PMID- 20141436
TI  - Clinical characteristics and outcomes of adults with Philadelphia chromosome
      positive and/or bcr-abl positive acute lymphoblastic leukemia: a single center
      study from China.
AB  - The study reviewed 389 adult patients with acute lymphoblastic leukemia (ALL) and
      110 patients (28.3%) were diagnosed as Philadelphia chromosome positive (Ph
      positive) and/or bcr-abl positive ALL. The special group had the same clinical
      characteristics as other studies, except for relatively young age and high
      incidence of both P190 and P210 fusion proteins expression. The complete
      remission (CR) rate in conventional chemotherapy (CT) group and in chemotherapy
      combined with imatinib (ICT) group was 84.7% and 96.0%, respectively. The 2-year
      disease-free survival (DFS) and overall survival (OS) were 0 and 23.6 +/- 6.9%,
      respectively in CT group; the 2-year DFS and OS were 22.1 +/- 8.8% and 41.6 +/-
      10.0%, respectively in ICT group; and in allogeneic stem cell transplantation
      (SCT) group, the 2-year DFS and OS were 48.2 +/- 13.9% and 53.1 +/- 12.7%,
      respectively. The results of the study indicated that introducing imatinib into
      treatment of patients with Ph-positive ALL could improve CR rate and survival,
      especially as early as possible, and allogenic SCT was still the first choice for
      these patients if they had suitable donors.

PMID- 20141437
TI  - HHV-6 and atypical lymphoproliferative disorders: are only qualitative molecular
      examinations sufficient to support a pathogenetic role?

PMID- 20141438
TI  - Paraneoplastic autoimmune cytopenias in Hodgkin lymphoma.
AB  - Autoimmune cytopenias are typical paraneoplastic phenomena in malignant
      lymphomas. We assessed the occurrence, clinical, and laboratory features as well
      as the response to treatment of autoimmune hemolytic anemia, autoimmune
      thrombocytopenia, and neutropenia in published cases of Hodgkin lymphomas (HL).
      We identified 34 cases of an association between HL and autoimmune hemolytic
      anemia and 48 cases of an association of autoimmune thrombocytopenia (AITP) and
      HL. The autoimmune cytopenias (AIC) may occur prior to, concurrent with, at the
      time of recurrence of lymphoma or in complete remission after treatment. Almost
      all autoimmune hemolytic anemias were caused by warm antibodies. Patients with HL
      with AIC are more commonly males and are more likely to have mixed cellularity
      (MC) HL. HL is the only lymphoma which may be associated with autoimmune
      neutropenia. In contrast to AIC in diffuse large B-cell lymphoma (DLBCL), early
      stage is less common in patients with HL with AIC. AIC in HL respond better to
      antilymphoma treatment than to steroids, with the exception of post-treatment
      AITP in CR of HL which responds easily and durably to steroids.

PMID- 20141439
TI  - A phase II study of alemtuzumab, fludarabine, cyclophosphamide, and doxorubicin
      (Campath-FCD) in peripheral T-cell lymphomas.
AB  - The clinical course of peripheral T-cell lymphoma (PTCL) is usually aggressive
      and the prognosis unfavorable. Therefore, there is a need for improvement of
      treatment options. Patients with newly diagnosed (n = 27) or refractory/relapsed
      (n = 11) PTCL received a combination of alemtuzumab, fludarabine,
      cyclophosphamide, and doxorubicin. The overall response rate (ORR) was 61%, with
      a complete response rate of 39%. In newly diagnosed patients the ORR was 63%, the
      median overall survival 25.9 months, and progression-free survival 11.8 months.
      In relapsed/refractory patients the median OS was 6.1 months. The most frequent
      grade 3/4 toxicities were leukopenia (95% of patients) and thrombocytopenia
      (58%). Cytomegalovirus (CMV) reactivation occurred in 12 patients, but only two
      had CMV disease. Treatment-related deaths occurred in six newly diagnosed
      patients and one with relapsed/refractory disease. In conclusion, Campath-FCD is
      active in PTCL but is associated with significant toxicity and is, therefore, not
      recommended for use or further study. Further studies are warranted to
      investigate other approaches to combining alemtuzumab with chemotherapy for the
      treatment of PTCL.

PMID- 20141440
TI  - Acute myeloid leukemia outcome: role of nucleotide excision repair polymorphisms
      in intermediate risk patients.
AB  - In acute myeloid leukemia (AML), cytogenetics predicts treatment outcome for the
      favorable and poor subgroups but not for the intermediate subgroup. Polymorphisms
      within the nucleotide excision repair (NER) pathway may lead to interindividual
      differences in DNA repair capacity, influencing outcome. We studied the role of
      six polymorphisms (ERCC1 Gln504Lys, XPD Lys751Gln, XPC Ala499Val, XPC Lys939Gln,
      XPG Asp1104His, and CCNH Val270Ala) in overall and disease-free survival among
      170 adult de novo patients with intermediate cytogenetics (diploid [n = 117]; non
      diploid [n = 53]), treated with induction chemotherapy. Kaplan-Meier and Cox
      proportional hazards models were performed. Diploid patients with the XPD AC/CC
      genotype survived shorter than those with the wild-type genotype (median survival
      22 vs. 40 months, p = 0.03). Diploid patients with XPC CT/TT genotype survived
      shorter than those with the wild-type genotype (median survival 15 vs. 30 months,
      p = 0.02). After adjusting for clinical and sociodemographic variables, patients
      carrying both XPD AC/CC and XPC CT/TT had a greater than two-fold increased risk
      of dying, compared to those with the wild-type genotypes (HR = 2.49; 95% CI: 1.06
      5.85). No associations were observed for disease-free survival. This combined
      genotype may modulate treatment effect, decreasing overall survival. These
      findings could in the future help select treatments for patients with normal
      cytogenetics.

PMID- 20141441
TI  - Oral Epstein-Barr virus-related B-cell lymphoma causing persistent paraneoplastic
      dermatomyositis after nasopharyngeal and cutaneous carcinomas.

PMID- 20141442
TI  - 18-Fluoro-deoxyglucose positron emission tomography report interpretation as
      predictor of outcome in diffuse large B-cell lymphoma including analysis of
      'indeterminate' reports.
AB  - This study evaluates the predictive value of post-therapy 18-fluoro-deoxyglucose
      positron emission tomography (FDG-PET), including indeterminate studies,
      following curative-intent therapy in diffuse large B-cell lymphoma (DLBCL).
      Consecutive patients from September 2002 to December 2005 were prospectively
      offered enrollment in an observational registry. Available FDG-PET reports after
      primary therapy were interpreted by hematologist-oncologists as positive,
      negative, or indeterminate. One hundred twenty-five patients with DLBCL had a
      median follow-up of 35.2 months. Ninety-three percent were treated with R-CHOP
      like therapy. Twenty percent of PET reports were judged indeterminate. Event-free
      survival (EFS) at 3 years for the negative and indeterminate groups was 85% and
      71%, respectively (p = 0.28 by log-rank). Overall survival (OS) at 3 years for
      negative, indeterminate, and positive groups was 89%, 88%, and 48%. Combining the
      pre-therapy International Prognostic Index (IPI) with the post-therapy FDG-PET
      result added to the predictive value of the study for patients. Three-year EFS
      for patients with low or low-intermediate IPI risk and an indeterminate FDG-PET
      report was 93%, while for those with high or high-intermediate pre-therapy IPI
      the 3-year EFS was 45% (p < 0.02). Interpreting FDG-PET reports following
      curative-intent chemotherapy in patients is informative but imprecise, and
      incorporation of pre-therapy prognosis can improve predictive utility.

PMID- 20141443
TI  - Interpretation and validation of interim positron emission tomography in Hodgkin
      lymphoma.

PMID- 20141444
TI  - Human Immunodeficiency Virus-associated anaplastic large cell lymphoma.
AB  - Anaplastic large cell lymphoma (ALCL) is a distinct subtype of peripheral T-cell
      lymphoma (PTCL) characterized by the expression of CD30 in lymphoma cells. Like
      aggressive B-cell non-Hodgkin lymphoma, the risk of developing PTCL is also
      increased in the setting of HIV infection. To date, the occurrence of ALCL in HIV
      positive individuals is limited to a few case reports and small case series. A
      total of 37 cases of HIV-associated ALCL were identified after reviewing the
      available published literature. Analysis of these cases showed that this group of
      HIV-infected patients was on average 38 years of age with a male-to-female ratio
      of 4:1, and a reported median CD4 cell count of 83 cells/mm(3). HIV-associated
      ALCL cells rarely expressed anaplastic lymphoma kinase. Epstein-Barr virus
      infection was associated with one-third of the cases. These lymphomas manifested
      almost exclusively with extranodal involvement and exhibited a very aggressive
      clinical course. The median overall survival was 5 months. The administration of
      chemotherapy and early stages at presentation were identified as good prognostic
      factors, while the use of HAART showed a statistical trend toward improved
      survival in HIV-associated ALCL.

PMID- 20141445
TI  - Telbivudine use in a patient affected by occult hepatitis B virus and B-cell non
      Hodgkin lymphoma.

PMID- 20141446
TI  - Am80 inhibits stromal cell-derived factor-1-induced chemotaxis in T-cell acute
      lymphoblastic leukemia cells.
AB  - C-X-C motif chemokine receptor 4 (CXCR4) and stromal cell-derived factor-1 (SDF
      1) play a potent role in metastasis and infiltration of many types of tumors,
      including T-cell acute lymphoblastic leukemia (T-ALL), into the central nervous
      system or lymph nodes. Although higher levels of CXCR4 expression have been shown
      to correlate with shorter survival of patients, effective drugs affecting cell
      surface CXCR4 expression are still unknown. In the present study, we examined the
      effects of a synthetic retinoid Am80 on CXCR4 expression of cultured T-ALL cells,
      such as Jurkat. Am80 inhibited surface CXCR4 expression and SDF-1-induced
      chemotaxis by the acceleration of CXCR4 internalization via activation of
      conventional PKC. Am80 may be an effective drug to inhibit the extramedullary
      infiltration of T-ALL cells.

PMID- 20141447
TI  - The efficacy and stem cell toxicity of cladribine and rituximab in the treatment
      of patients with chronic lymphocytic leukemia: are all purine analogs created
      equal?

PMID- 20141448
TI  - In vitro skin permeation of hinokitiol loaded in vesicles composed of
      behenyltrimethylammonium chloride and stearic acid.
AB  - INTRODUCTION: Behenyltrimethylammonium chloride (BTAC) and stearic acid (SA)
      could be associated with each other through salt bridges, and the associated
      BTAC/SA could build bilayer vesicles with the aid of hinokitiol (HKL). METHOD:
      The vesicles were prepared by a precipitation method and used to enhance the skin
      permeation of HKL. RESULTS: In case the molar ratio of BTAC/SA/HKL was 1/1/0, no
      vesicle was observed on transmission electron microscope photos. When the molar
      ratio of BTAC/SA/HKL was 1/1/0.4, vesicle was observed together with some
      agglomerates. When the content of HKL increased to the ratios of 1/1/0.8 and
      1/1/1.2, vesicles were exclusively observed. In vitro fluxes for 18 hours through
      hairless mouse skin of HKL dissolved in alcoholic solutions were less than 1
      mg/cm2/h. Whereas the fluxes of HKL encapsulated in the vesicles were about three
      times higher than that of HKL in the alcoholic solutions. CONCLUSION: The
      vesicles could be used for the hair growth promotion.

PMID- 20141449
TI  - Self-help groups and mental health/substance use agencies: the benefits of
      organizational exchange.
AB  - Self-help groups benefit clients by linking them to people who have "been there"
      and are successfully coping with their situations. Mental health/substance use
      agencies can increase access to evidence-based benefits of self-help groups by
      engaging them in organizational exchanges. Organizational theories are used to
      frame beneficial exchanges with self-help groups. Adaptational theory is used to
      frame exchanges with self-help groups and various service agency subunits, e.g.,
      board, practitioner, and client units. Institutional theory is used to frame
      joint agency/self-help initiatives to promote community acceptance of self-help
      groups, which in turn may enhance the credibility of the professional agency.

PMID- 20141450
TI  - Legal highs on the Internet.
AB  - This article describes the findings of a descriptive analysis of 27 online drug
      retailers selling legal alternatives to illegal drugs, commonly referred to as
      "herbal highs" and "legal highs" in 2008 . The study attempted to quantify the
      online availability of drug retailers, to describe common products and
      characteristics in EU-based retail sales. The findings highlight the concern
      about the lack of objective information about products offered, including
      potential risks to health. Systems should be developed to assess the contents of
      products and the accuracy of information provided on the Internet, alongside
      continued monitoring of this market for "legal high" substances.

PMID- 20141451
TI  - Alcohol-related help-seeking in problem drinking women sexual assault survivors.
AB  - In 2002-2003 correlates of alcohol-related help-seeking were studied in women
      sexual assault survivors who were current problem drinkers (N = 526) in a large
      metropolitan area. Volunteer participants completed several valid and reliable
      instruments (i.e., the TWEAK, GFM, and MAST), which assessed alcohol use and
      misuse and related help-seeking. Data were analyzed using logistic regression
      models. Results suggest that correlates of women survivors' alcohol-related help
      seeking vary depending on the specific source. Limitations and implications are
      noted and recommendations for future research are made. This study was funded by
      the National Institutes on Alcohol Abuse and Alcoholism.

PMID- 20141453
TI  - Factors related to injection drug use among female prisoners.
AB  - Female inmates (N = 655) of a large prison facility in the southeastern United
      States were surveyed about their substance use, social histories, and
      demographics. Multinomial logistic regression was used to identify predictors of
      injection drug use. The sample was primarily young (M = 34 +/- 9 years), and
      evenly split on race (45.3% White and 44.6% Black). Four predictors were
      identified as significant risk factors for injection drug use: being White,
      having a prior history of substance user treatment, having a prior drug-related
      charge, and being a problem drinker. Implications, limitations, and future
      directions are discussed.

PMID- 20141452
TI  - The profile of injection drug users in Chennai, India: identification of risk
      behaviours and implications for interventions.
AB  - We characterize the demographics, injection practices and risk behaviours of
      1,158 injection drug users (IDUs) in Chennai, the capital of Tamil Nadu in
      southern India, who were recruited during 2005-2006 by community outreach. The
      median age was 35 years; the majority of IDUs were male, of Tamil ethnicity and
      married, and earning less than US$75 per month. Most (76%) had injected in the
      prior month. The median age at first injection was 25 years; the most common drug
      injected was heroin (80%) followed by buprenorphine. High risk behaviours were
      common and included needle-sharing, unsafe disposal, and inappropriate cleaning
      of needles as well as limited condom use. IDUs in India need to be educated on
      harm reduction and safe-injection practices; Pharmacies could serve as potential
      venues for HIV prevention interventions among IDUs in India, as most IDUs obtain
      their needles from pharmacies without prescription.

PMID- 20141454
TI  - Single-session motivational interviewing for drug detoxification inpatients:
      effects on self-efficacy, stages of change and substance use.
AB  - Thirty-five inpatients at a Stockholm hospital drug user detoxification unit
      received single-session Motivational Interviewing (MI) between 2006 and 2008. At
      baseline and after 3 months, they were compared to a semi-randomized control
      group of 52 patients with treatment as usual. In the MI group, self-efficacy
      increased regarding abstention in connection with positive feelings, appreciation
      of positive drug effects increased, and participants tended to transition toward
      preparation/action stages of change. Despite implementation challenges, the study
      demonstrates the feasibility and effectiveness of single-session MI delivery in
      the inpatient drug detoxification setting and suggests paths for future research
      on delivery of single-session MI.

PMID- 20141455
TI  - Increasing the use of nicotine replacement therapy by a simple intervention: an
      exploratory trial.
AB  - This historical cohort study conducted in a University Hospital between 2004 and
      2006 included 322 smokers willing to quit and assessed whether adding a teaching
      session on nicotine addiction to a smoking cessation program could increase the
      proportion of participants using pharmacotherapy. The control cohort received the
      standard course while two short talks were added to the course for a consecutive
      intervention cohort. These talks used the metaphor of a pizza delivery service to
      explain neural mechanisms underlying nicotine addiction. Medication use was
      significantly more common in the intervention than control cohort (82.1% vs.
      51.2%; adjusted odds ratio 4.0; 2.34-6.83).

PMID- 20141456
TI  - Training drug treatment patients to conduct peer-based HIV outreach: an
      ethnographic perspective on peers' experiences.
AB  - From 2005 to 2008, the Bienvenidos Project trained Puerto Rican patients of New
      York City and New Jersey Methadone Maintenance Treatment Programs to conduct peer
      based community outreach to migrant Puerto Rican drug users to reduce migrants'
      HIV risk behaviors. Ethnographic research, including focus groups, individual
      interviews, and observations, was conducted with a subset of the patients trained
      as peers (n = 49; 67% male; mean age 40.3 years) to evaluate the self-perceived
      effects of the intervention. Results of the ethnographic component of this study
      are summarized. The role of ethnographic methods in implementing and evaluating
      this kind of intervention is also discussed.

PMID- 20141457
TI  - Comparing probability and non-probability sampling methods in Ecstasy research:
      implications for the internet as a research tool.
AB  - The usage of Ecstasy and related drug (ERD) has increasingly been the focus of
      epidemiological and other public health-related research. One of the more
      promising methods is the use of the Internet as a recruitment and survey tool.
      However, there remain methodological concerns and questions about
      representativeness. Three samples of ERD users in Melbourne, Australia surveyed
      in 2004 are compared in terms of a number of key demographic and drug use
      variables. The Internet, face-to-face, and probability sampling methods appear to
      access similar but not identical groups of ERD users. Implications and
      limitations of the study are noted and future research is recommended.

PMID- 20141459
TI  - Are you going to finish that drink?
AB  - Data are from the 2000 National Alcohol Survey Methodological Follow-up, which
      includes 323 individuals from across the United States. Directly measured
      estimates of drink volume and amount left unfinished along with self-report of
      the frequency and reasons for which drinks are not finished and are compared
      across groups. Overall, 12% of drinks reported in the sample were not finished.
      Smaller amounts of beer and wine volume were left by men, "heavier drinkers" and
      older persons. This research was supported by grant P-30-A05595 to the Alcohol
      Research Group, Public Health Institute from the National Institute on Alcohol
      Abuse and Alcoholism (NIAAA).

PMID- 20141458
TI  - Adverse events and substance use among female adolescent offenders: effects of
      coping and family support.
AB  - This study examined a stress-coping model for substance use among female
      adolescents (N = 305, 69% African American) involved in the Mississippi juvenile
      justice system. Participants were interviewed in 2006 , regarding exposure to
      adverse and traumatic events, and they completed self-administered measures of
      social support from relatives, coping strategies, and questions on frequency of
      alcohol and other drug use. Results from nested regression models revealed that
      stressors are associated with drug, but not alcohol use. The use of supportive
      kinship ties and religion to cope were protective factors. The implications and
      limitations of the study are discussed.

PMID- 20141460
TI  - Estimating the determinants of smoking behavior in Taiwan.
AB  - This paper investigates the determinants of the smoking behavior of people in
      Taiwan based on data obtained from the 2004 Taiwan Panel Study of Family
      Dynamics. The sample size consists of 3,015 individuals whose ages range from 33
      to 75. Probit models are estimated separately for the smoking behavior equations.
      The results indicate that gender, marital status, age, health, employment, and
      the presence of young children have a relatively important impact on an
      individual's smoking behavior. In addition, the results of the estimated
      predictors, such as having higher educational attainment, having smoking family
      members and smoking peers, and being aware of the harmful effects of smoking,
      also bring to light crucial policy implications. Study limitations are noted.

PMID- 20141461
TI  - Methadone maintenance patients' knowledge, attitudes, beliefs, and experiences
      concerning treatment for hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) knowledge, attitudes, beliefs, and experiences (KABE) of
      64 HCV antibody positive methadone maintenance treatment (MMT) patients were
      assessed in conjunction with acceptability of an on-site semi-structured HCV
      education session, HCV RNA diagnostic testing, HCV treatment motivational
      assessment, and initiation of HCV treatment. The KABE interviews were conducted
      in 2006 and 2007 in an urban New York State MMT clinic in affiliation with a NIDA
      funded HCV research project. The majority had basic knowledge of HCV disease, but
      poor understanding of HCV testing and treatment. While the majority of
      participants expressed fear of HCV treatment side effects, 88% accepted HCV RNA
      testing and 78% expressed willingness to start HCV treatment with the majority of
      chronically infected choosing to start HCV treatment medications. Study
      limitations and implications are discussed.

PMID- 20141462
TI  - Nonmedical use of promethazine hydrochloride among heroin injectors in Vietnam:
      unrecognized risks and unintended consequences.
AB  - BACKGROUND: Surveillance studies have noted intravenous injection of promethazine
      hydrochloride (PHC) among populations that use heroin in south and southeast
      Asia. However, little is known about onset and initiation of PHC use and its
      relationship to habitual heroin use. METHODS: As part of a longitudinal study of
      heroin initiation, a sample of 179 new heroin users, aged 15-27 years, were
      interviewed between October 2005 and December 2006 in Hanoi, Vietnam. Cox
      proportional hazard regression analysis was used to characterize age at
      promethazine initiation and its association with relevant covariates. RESULTS:
      76% reported lifetime use of PHC. Mean age of PHC initiation was 21.3 years, on
      average 6 months following onset of heroin injection. In multivariate analysis,
      lifetime use of diazepam [HR = 1.69 (1.17, 2.44); p-value = .01] and injecting
      heroin for more than 1.58 years [HR = 1.46 (1.04, 2.06); p-value = .03] were
      associated with PHC initiation. CONCLUSION: Intravenous injection of PHC is a
      relatively common practice among young injection heroin users in Hanoi, Vietnam
      who use it on a situational basis to substitute for heroin (when heroin is not
      available or when heroin is too costly) or to augment the effects of an
      inadequate heroin dosing (delaying onset of heroin withdraw). Existing drug
      prevention strategies in Vietnam are focused primarily on heroin and most new
      heroin users initiate PHC use without prior knowledge of its high risk for
      serious vein damage. Future research is needed on the PHC use among heroin users,
      including long-term medical consequences of PHC exposure.

PMID- 20141463
TI  - The social consequences of binge drinking among 24- to 32-year-olds in six
      European countries.
AB  - Data were available from general population surveys carried out in six countries
      in the years 2000 to 2005 under the auspices of Gender, Alcohol and Culture: An
      International Study (GENACIS). A total of 2089 adults aged 24-32 in the Czech
      Republic, Denmark, the Isle of Man, Spain, Sweden, and the United Kingdom (UK)
      responded to questions about their drinking habits and social consequences
      directly resulting from their drinking. Survey methods varied from quota sampling
      with face-to-face interviewing in Spain and the UK to telephone surveys in
      Denmark and Sweden. Response rates varied from 50% to 72%. "Binge drinking"
      defined as a usual amount of more than 8 UK "units" for men and more than 6 units
      for women was more likely than moderate drinking to lead to social consequences,
      fights, or being asked to cut down on drinking. There were highly significant
      differences between the countries both in the percentages of "heavy" drinkers and
      in the adverse consequences of binge drinking. In Spain, the UK, and the Czech
      Republic binge drinking was more likely to lead to adverse consequences than was
      binge drinking in the other three countries. Male gender, low educational level,
      high drinking frequency, and single marital status were also significantly
      associated with adverse social consequences from drinking, but none of these
      variables explained the country differences. The presence of children had little
      effect.

PMID- 20141464
TI  - Substance use and misuse among Slovenian table tennis players.
AB  - Substance use and misuse (SU&M) is regularly studied in sports, but we have found
      no such data for table tennis. We have studied SU&M in athletes competing at the
      Slovenian Nationals 2008-2009 (responding rate was 100%; 50 males and 29 females;
      aged 18 years or older). The anonymous questionnaire for studying SU&M and
      corresponding educational, socio-demographic, and sport factors was used. More
      than 90% of all the athletes included in our study do not rely on coaches' and/or
      physicians' opinion regarding nutritional supplements and doping. Chi-square test
      revealed higher prevalence of binge drinking, cigarette smoking, and potential
      doping behavior in males. In both genders, with the advancement of the sport
      status, the probability for potential doping behavior increases. In conclusion,
      we strongly suggest permanent SU&M educational programs for table tennis athletes
      as well as for their coaches and physicians.

PMID- 20141465
TI  - The lasting effects of marijuana use on educational attainment in midlife.
AB  - Data from the NLSY79, a U.S. nationally representative longitudinal survey of
      labor market behavior, sponsored and directed by the Bureau of Labor Statistics
      of the U.S. Department of Labor, was used to assess the influence of marijuana
      use on educational attainment (N = 7,724). Multivariate nested OLS models
      assessed the associations of marijuana use in 1979, 1984, and 1998 with
      educational attainment in 2002. Adolescent, frequent, and persistent users
      experienced lower attainment at ages 37 to 45 than nonusers even when use was
      confined to adolescence. Implications of the findings, limitations of the study,
      and suggestions for future research are discussed.

PMID- 20141467
TI  - Patients with dual diagnoses or substance use disorders only: 12-step group
      participation and 1-year outcomes.
AB  - We compared outpatients (regional facility) with substance use and psychiatric (N
      = 199) or only substance use (N = 146) disorders on baseline and one-year
      symptoms (93% follow-up), and treatment and 12-step group participation over the
      year (2005). We examined whether diagnostic status moderated associations between
      participation and outcomes (Addiction Severity Index) with regressions. At follow
      up, dual diagnosis patients had more severe symptoms, despite comparable
      treatment. The groups were comparable on 12-step participation, which was
      associated with better outcomes. However, associations of participation with
      better outcomes were weaker for dual diagnosis patients. Study (VA HSR&D-funded)
      implications and limitations are noted and research suggested.

PMID- 20141468
TI  - Longitudinal outcomes for treated opiate use and the use of ancillary medical and
      social services.
AB  - Using an extended Maudsley Addiction Profile, 404 opiate users entering treatment
      across Ireland were interviewed at intake and at 1 year and 3 years between 2003
      and 2006. At 3 years clients were abstinent, in treatment, or relapsed. Analysis
      of lifetime use of treatment services revealed that greater proportions of those
      who were drug free at 3 years had counselling in the past. Multiple regression
      revealed that the number of previous treatment episodes had a significant
      positive effect on outcomes. Findings are important during times of financial
      constraint when treatment providers are under pressure to cut back to core
      services.

PMID- 20141466
TI  - Performance of the alcohol use disorders identification test among tuberculosis
      patients in Russia.
AB  - The alcohol use disorders identification test (AUDIT), a screening instrument to
      identify individuals at risk of alcohol use-related problems, has not been
      validated in a Russian primary care population. We assessed the reliability,
      factor structure, sensitivity, and specificity of AUDIT scores among 254 subjects
      initiating tuberculosis treatment from 2005 to 2007 in Tomsk City. Our findings
      support the use of the AUDIT as a screening instrument among Russian individuals
      seeking primary care. We discuss implications, limitations, and future research.

PMID- 20141471
TI  - Learning to represent spatial transformations with factored higher-order
      Boltzmann machines.
AB  - To allow the hidden units of a restricted Boltzmann machine to model the
      transformation between two successive images, Memisevic and Hinton (2007)
      introduced three-way multiplicative interactions that use the intensity of a
      pixel in the first image as a multiplicative gain on a learned, symmetric weight
      between a pixel in the second image and a hidden unit. This creates cubically
      many parameters, which form a three-dimensional interaction tensor. We describe a
      low-rank approximation to this interaction tensor that uses a sum of factors,
      each of which is a three-way outer product. This approximation allows efficient
      learning of transformations between larger image patches. Since each factor can
      be viewed as an image filter, the model as a whole learns optimal filter pairs
      for efficiently representing transformations. We demonstrate the learning of
      optimal filter pairs from various synthetic and real image sequences. We also
      show how learning about image transformations allows the model to perform a
      simple visual analogy task, and we show how a completely unsupervised network
      trained on transformations perceives multiple motions of transparent dot patterns
      in the same way as humans.

PMID- 20141472
TI  - Bayesian inference based on stationary Fokker-Planck sampling.
AB  - A novel formalism for bayesian learning in the context of complex inference
      models is proposed. The method is based on the use of the stationary Fokker
      Planck (SFP) approach to sample from the posterior density. Stationary Fokker
      Planck sampling generalizes the Gibbs sampler algorithm for arbitrary and unknown
      conditional densities. By the SFP procedure, approximate analytical expressions
      for the conditionals and marginals of the posterior can be constructed. At each
      stage of SFP, the approximate conditionals are used to define a Gibbs sampling
      process, which is convergent to the full joint posterior. By the analytical
      marginals efficient learning methods in the context of artificial neural networks
      are outlined. Offline and incremental bayesian inference and maximum likelihood
      estimation from the posterior are performed in classification and regression
      examples. A comparison of SFP with other Monte Carlo strategies in the general
      problem of sampling from arbitrary densities is also presented. It is shown that
      SFP is able to jump large low-probability regions without the need of a careful
      tuning of any step-size parameter. In fact, the SFP method requires only a small
      set of meaningful parameters that can be selected following clear, problem
      independent guidelines. The computation cost of SFP, measured in terms of loss
      function evaluations, grows linearly with the given model's dimension.

PMID- 20141473
TI  - Norm-observable operator models.
AB  - Hidden Markov models (HMMs) are one of the most popular and successful
      statistical models for time series. Observable operator models (OOMs) are
      generalizations of HMMs that exhibit several attractive advantages. In
      particular, a variety of highly efficient, constructive, and asymptotically
      correct learning algorithms are available for OOMs. However, the OOM theory
      suffers from the negative probability problem (NPP): a given, learned OOM may
      sometimes predict negative probabilities for certain events. It was recently
      shown that it is undecidable whether a given OOM will eventually produce such
      negative values. We propose a novel variant of OOMs, called norm-observable
      operator models (NOOMs), which avoid the NPP by design. Like OOMs, NOOMs use a
      set of linear operators to update system states. But differing from OOMs, they
      represent probabilities by the square of the norm of system states, thus
      precluding negative probability values. While being free of the NPP, NOOMs retain
      most advantages of OOMs. For example, NOOMs also capture (some) processes that
      cannot be modeled by HMMs. More importantly, in principle, NOOMs can be learned
      from data in a constructive way, and the learned models are asymptotically
      correct. We also prove that NOOMs capture all Markov chain (MC) describable
      processes. This letter presents the mathematical foundations of NOOMs, discusses
      the expressiveness of the model class, and explains how a NOOM can be estimated
      from data constructively.

PMID- 20141474
TI  - Decision confidence and uncertainty in diffusion models with partially correlated
      neuronal integrators.
AB  - Diffusion models have become essential for describing the performance and
      statistics of reaction times in human decision making. Despite their success, it
      is not known how to evaluate decision confidence from them. I introduce a broader
      class of models consisting of two partially correlated neuronal integrators with
      arbitrarily time-varying decision boundaries that allow a natural description of
      confidence. The dependence of decision confidence on the state of the losing
      integrator, decision time, time-varying boundaries, and correlations is
      analytically described. The marginal confidence is computed for the half
      anticorrelated case using the exact solution of the diffusion process with
      constant boundaries and compared to that of the independent and completely
      anticorrelated cases.

PMID- 20141475
TI  - Timescale-invariant pattern recognition by feedforward inhibition and parallel
      signal processing.
AB  - The timescale-invariant recognition of temporal stimulus sequences is vital for
      many species and poses a challenge for their sensory systems. Here we present a
      simple mechanistic model to address this computational task, based on recent
      observations in insects that use rhythmic acoustic communication signals for mate
      finding. In the model framework, feedforward inhibition leads to burst-like
      response patterns in one neuron of the circuit. Integrating these responses over
      a fixed time window by a readout neuron creates a timescale-invariant stimulus
      representation. Only two additional processing channels, each with a feature
      detector and a readout neuron, plus one final coincidence detector for all three
      parallel signal streams, are needed to account for the behavioral data. In
      contrast to previous solutions to the general time-warp problem, no time delay
      lines or sophisticated neural architectures are required. Our results suggest a
      new computational role for feedforward inhibition and underscore the power of
      parallel signal processing.

PMID- 20141476
TI  - Reward-modulated Hebbian learning of decision making.
AB  - We introduce a framework for decision making in which the learning of decision
      making is reduced to its simplest and biologically most plausible form: Hebbian
      learning on a linear neuron. We cast our Bayesian-Hebb learning rule as
      reinforcement learning in which certain decisions are rewarded and prove that
      each synaptic weight will on average converge exponentially fast to the log-odd
      of receiving a reward when its pre- and postsynaptic neurons are active. In our
      simple architecture, a particular action is selected from the set of candidate
      actions by a winner-take-all operation. The global reward assigned to this action
      then modulates the update of each synapse. Apart from this global reward signal,
      our reward-modulated Bayesian Hebb rule is a pure Hebb update that depends only
      on the coactivation of the pre- and postsynaptic neurons, not on the weighted sum
      of all presynaptic inputs to the postsynaptic neuron as in the perceptron
      learning rule or the Rescorla-Wagner rule. This simple approach to action
      selection learning requires that information about sensory inputs be presented to
      the Bayesian decision stage in a suitably preprocessed form resulting from other
      adaptive processes (acting on a larger timescale) that detect salient
      dependencies among input features. Hence our proposed framework for fast learning
      of decisions also provides interesting new hypotheses regarding neural nodes and
      computational goals of cortical areas that provide input to the final decision
      stage.

PMID- 20141477
TI  - Efficient continuous-time asymmetric Hopfield networks for memory retrieval.
AB  - A novel m energy functions method is adopted to analyze the retrieval property of
      continuous-time asymmetric Hopfield neural networks. Sufficient conditions for
      the local and global asymptotic stability of the network are proposed. Moreover,
      an efficient systematic procedure for designing asymmetric networks is proposed,
      and a given set of states can be assigned as locally asymptotically stable
      equilibrium points. Simulation examples show that the asymmetric network can act
      as an efficient associative memory, and it is almost free from spurious memory
      problem.

PMID- 20141478
TI  - Fast and exact simulation methods applied on a broad range of neuron models.
AB  - Recently van Elburg and van Ooyen (2009) published a generalization of the event
      based integration scheme for an integrate-and-fire neuron model with
      exponentially decaying excitatory currents and double exponential inhibitory
      synaptic currents, introduced by Carnevale and Hines. In the paper, it was shown
      that the constraints on the synaptic time constants imposed by the Newton-Raphson
      iteration scheme, can be relaxed. In this note, we show that according to the
      results published in D'Haene, Schrauwen, Van Campenhout, and Stroobandt (2009), a
      further generalization is possible, eliminating any constraint on the time
      constants. We also demonstrate that in fact, a wide range of linear neuron models
      can be efficiently simulated with this computation scheme, including neuron
      models mimicking complex neuronal behavior. These results can change the way
      complex neuronal spiking behavior is modeled: instead of highly nonlinear neuron
      models with few state variables, it is possible to efficiently simulate linear
      models with a large number of state variables.

PMID- 20141479
TI  - Conditional mixture model for correlated neuronal spikes.
AB  - Analysis of correlated spike trains is a hot topic of research in computational
      neuroscience. A general model of probability distributions for spikes includes
      too many parameters to be of use in analyzing real data. Instead, we need a
      simple but powerful generative model for correlated spikes. We developed a class
      of conditional mixture models that includes a number of existing models and
      analyzed its capabilities and limitations. We apply the model to dynamical
      aspects of neuron pools. When Hebbian cell assemblies coexist in a pool of
      neurons, the condition is specified by these assemblies such that the probability
      distribution of spikes is a mixture of those of the component assemblies. The
      probabilities of activation of the Hebbian assemblies change dynamically. We used
      this model as a basis for a competitive model governing the states of assemblies.

PMID- 20141480
TI  - General Poisson exact breakdown of the mutual information to study the role of
      correlations in populations of neurons.
AB  - We present an integrative formalism of mutual information expansion, the general
      Poisson exact breakdown, which explicitly evaluates the informational
      contribution of correlations in the spike counts both between and within neurons.
      The formalism was validated on simulated data and applied to real neurons
      recorded from the rat somatosensory cortex. From the general Poisson exact
      breakdown, a considerable number of mutual information measures introduced in the
      neural computation literature can be directly derived, including the exact
      breakdown (Pola, Thiele, Hoffmann, & Panzeri, 2003), the Poisson exact breakdown
      (Scaglione, Foffani, Scannella, Cerutti, & Moxon, 2008) the synergy and
      redundancy between neurons (Schneidman, Bialek, & Berry, 2003), and the
      information lost by an optimal decoder that assumes the absence of correlations
      between neurons (Nirenberg & Latham, 2003; Pola et al., 2003). The general
      Poisson exact breakdown thus offers a convenient set of building blocks for
      studying the role of correlations in population codes.

PMID- 20141482
TI  - Secular change in muscular strength of indigenous rural youth 6-17 years in
      Oaxaca, southern Mexico: 1968-2000.
AB  - OBJECTIVE: The study compared the grip strength of indigenous school youth 6-17
      years of age in Oaxaca, southern Mexico, who were surveyed in 1968, 1978 and
      2000. METHODS: Grip strength (Smedley/Stoelting) was measured to 0.5 kg in 1280
      children and adolescent, 621 males and 659 females, in the three surveys. Height
      and weight were also measured. Strength of the right and left hands was summed to
      provide a general estimate of muscular strength. Summed grip strength was also
      expressed per unit body mass (kg/kg) and height (kg/m). Subjects were classified
      into four age groups: 6-8 years (childhood), 9-11 years (transition in
      adolescence), 12-14 years (early adolescence) and 15-17 years (later
      adolescence). Children 6-14 years were surveyed in 1968, 1978 and 2000 while
      adolescents 15-17 years were surveyed in 1978 and 2000. Sex-specific MANCOVAs
      were used for comparisons among years within age groups. RESULTS: Changes in grip
      strength between 1968 and 1978 among children 6-14 years were small and
      significant only in girls. Grip strength increased, on average, between 1978 and
      2000 in boys 6-17 years but only in girls 6-14 years; adolescent girls 15-17
      years in 1978 were stronger than those in 2000. Secular gains in muscular
      strength were generally proportional to secular gains in body weight and height.
      CONCLUSION: The data demonstrate secular changes in muscular strength in
      indigenous rural youth in a community in the process of transition from
      subsistence level agriculture to an economy less dependent upon agriculture.

PMID- 20141481
TI  - Surfactant protein D binding to Aspergillus fumigatus hyphae is calcineurin
      sensitive.
AB  - Surfactant protein D (SP-D) plays a central role in pulmonary innate immune
      responses to microbes and allergens, often enhancing clearance of inhaled
      material. Although SP-D functions during bacterial and viral infections are well
      established, much less is known about its possible roles during invasive fungal
      infections. Aspergillus fumigatus is a prominent fungal pathogen in
      immunocompromised individuals, and can cause allergic or invasive aspergillosis.
      SP-D has been shown to be protective against both of these disease modalities.
      The moieties present on the fungal surface responsible for SP-D binding remain
      largely unclear, although cell wall 1,3-beta-D-glucan is bound by SP-D in other
      fungal species. There is little information regarding the interaction of SP-D
      with A. fumigatus hyphae which are responsible for the invasive form of disease.
      Here, we show that SP-D binding to A. fumigatus hyphae is sensitive to the
      activity of the calcium-activated protein phosphatase calcineurin. Deletion of
      the catalytic subunit calcineurin A (DeltacnaA) or pharmacologic inhibition of
      calcineurin through FK506 abrogated SP-D binding. In contrast, SP-D binding to
      Cruptococcus neoformans was calcineurin-independent. Pharmacologic inhibition of
      A. fumigatus cell wall components by caspofungin (inhibits 1,3-beta-D-glucan
      synthesis) and nikkomycin Z (inhibits chitin synthesis) increased SP-D binding to
      the wild-type strain. In contrast, SP-D binding increased in the DeltacnaA strain
      only after nikkomycin Z treatment. We conclude that SP-D binding to A. fumigatus
      hyphae is calcineurin-sensitive, presumably as a consequence of calcineurin's
      role in regulating production of key cell wall binding partners, such as 1,3-beta
      D-glucan. Elucidation of the interaction between lung innate immune factors and
      A. fumigatus could lead to the development of novel therapeutic interventions.

PMID- 20141483
TI  - Body mass index, waist-to-hip ratio and waist/height in adult population from
      Backa and Banat - the Republic of Serbia.
AB  - BACKGROUND: Nutritional status is vital in the assessment of physical fitness and
      health status of populations. AIM: This study aimed to describe relationships
      between BMI, waist-to-hip ratio (WHR) and waist/height (W/Ht) and factors such as
      education, residence, origin and ethnic belonging among adults in Backa and
      Banat. SUBJECTS AND METHODS: The study was conducted in 47 villages in the north
      of Serbia. The tested group consisted of 4247 individuals, aged 20+. RESULTS: The
      problem of overweight and obesity was more common among men (66%) than women
      (49.71%). In the group with normal BMI, the majority of men and women were
      characterized by normal WHR and W/Ht values, but among them there were also
      groups with incorrect WHR (males >or= 0.95, females >or= 0.8) and W/Ht (>or=
      0.5). Socio-demographic factors had a little impact on BMI, WHR and W/Ht in men
      in certain age groups while their impact was higher in women. These factors,
      especially education and origin, had a significant impact on nutritional status
      in young and middle-aged women, whereas they were not significant in older female
      participants (> 60). CONCLUSION: Despite the fact that this part of the country
      has undergone intensive social changes since the last decade of 20th century, the
      nutritional status of the population has not significantly changed.

PMID- 20141484
TI  - The interleukin-1 family gene polymorphisms in Korean patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: The interleukin (IL)-1 family and its related family members are
      primary inflammatory cytokines. The aim of this study was to assess the possible
      association between nine IL-1 family gene polymorphisms and rheumatoid arthritis
      (RA). METHODS: To investigate the genetic association between IL-1 family gene
      polymorphisms and the risk of RA in a Korean population, 69 single nucleotide
      polymorphisms (SNPs) of the nine IL-1 family gene regions were selected. A total
      of 806 subjects (498 controls and 308 RA patients) were included in the study.
      The genotypes of the selected SNPs in the IL-1 family genes were determined using
      Illumina Sentrix Array Matrix chips. SNP Stats, Haploview, and SNP Analyzer, and
      Helixtree programs were used for the analysis of the genetic data. RESULTS: We
      observed statistically significant associations between the SNPs of IL1F10 and
      IL1RN among the IL-1 family genes in the RA patients and the control population.
      When the patients were divided into two groups according to the parameters of
      disease activity, including C-reactive protein (CRP) level (> or = 0.5 or < 0.5
      mg/dL), the erythrocyte sedimentation rate (ESR) (> or = 30 or < 30 mm/h), and
      parameters of severity, including rheumatoid factor (RF), anti-cyclic
      citrullinated peptide (anti-CCP), and bone erosion (positive or not), we found
      significant associations between the parameters, including CRP, ESR, and bone
      erosion, and SNPs of the IL-1 family genes in RA. CONCLUSION: This study suggests
      that IL-1 family gene (IL1F10 and IL1RN) polymorphisms may play an important role
      in the susceptibility to developing RA.

PMID- 20141485
TI  - Self-reported food intolerance and mucosal reactivity after rectal food protein
      challenge in patients with rheumatoid arthritis.
AB  - OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an
      influence on arthritic symptoms by different diets has been reported. Our primary
      aim was to record the self-experienced adverse food reactions in patients with
      RA. A secondary aim was to relate self-experienced adverse reactions to dairy
      produce and wheat to the local mucosal reactivity observed after rectal challenge
      with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about
      self-experienced adverse reaction to food was sent to 347 RA patients. Rectal
      challenge with CM and gluten was performed in 27 of these patients and in healthy
      controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide
      (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic
      protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty
      seven per cent of the RA patients reported food intolerance (FI) to various
      foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity
      to CM was observed in 11% of the patients. Moderately increased mucosal
      reactivity to CM and gluten was found in 22% and 33%, respectively, of the
      patients. No relationship was found between self-experienced adverse reactions to
      CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI
      is reported frequently by RA patients, with a prevalence similar to that reported
      previously in the general population. Mucosal reactivity to CM and gluten is seen
      in a minor fraction of RA patients and is not related to the frequently perceived
      intolerance to these proteins.

PMID- 20141486
TI  - Heat shock protein expression is low in intestinal mucosa in juvenile idiopathic
      arthritis: a defect in immunoregulation?
AB  - OBJECTIVES: Heat shock proteins (HSPs) are involved in the regulation of
      inflammation and in the maintenance of mucosal integrity. Their altered
      expression may be a marker of mucosal inflammation and also contribute to tissue
      injury. The small intestinal mucosa in children with juvenile idiopathic
      arthritis (JIA) shows signs of intestinal immune activation, such as increased
      intraepithelial cytotoxic lymphocyte counts. To further evaluate the
      characteristics of this immune activation in JIA, we have studied the expression
      of several HSPs, major histocompatibility complex (MHC) class I-related chain A
      (MICA), and the heat shock transcription factor 1 (HSF1) in intestinal biopsies
      from children with JIA. METHODS: We studied 15 patients with JIA. Controls
      included 13 children without JIA, studied for various gastrointestinal (GI)
      symptoms, but eventually shown not to have any GI disease. The subjects were
      examined by endoscopy. The expression of HSP60, HSP70, MICA, and HSF1 was
      analysed in ileal and duodenal biopsies by using immunohistochemistry. RESULTS:
      The expression levels of HSP60, MICA, and HSF1 were significantly lower in the
      duodenal epithelium in the JIA patients compared to the controls. MICA and HSF1
      also showed lower expression in the ileal epithelium. The expression of HSP70 did
      not differ between the groups. CONCLUSIONS: The downregulation of HSP60, MICA,
      and HSF1 in small intestinal mucosa may indicate that intestinal epithelial cells
      show immune aberration in JIA. We speculate that the low heat shock response may
      play a role in the pathogenesis of JIA, interfering with mucosal integrity and
      local intestinal immunoregulation.

PMID- 20141487
TI  - Glycemic index of selected carbohydrate-based foods consumed in Qatar.
AB  - This study determined the glycemic index (GI) of selected carbohydrate-rich foods
      consumed in Qatar. Recruited volunteers (n = 19) consumed two reference foods,
      glucose and white bread, and 10 test foods. The foods tested for their GI were
      Fatayer (cheese, Zaatar, spinach), Tanour white bread, white basmati rice,
      Shearia, Muhalabea, Sago Awama and Qurs Aquili. Results of the study indicated
      that all of the foods tested had high GIs (> 70). Shearia had the highest GI
      (84.0 +/- 1.85) using the glucose scale, and Fatayer Spinach had the lowest GI
      (77.6 +/- 2.00). There was no significant correlation between the GI of all test
      foods, using glucose or white bread as standard foods, and the age or the body
      mass index of the volunteers (P > 0.05). The study provides data on the GIs of
      carbohydrate-based foods consumed in Qatar and other Arabian Gulf countries that
      have not been reported before.

PMID- 20141488
TI  - Temporal fine structure in cochlear implants: preliminary speech perception
      results in Cantonese-speaking implant users.
AB  - CONCLUSION: Acute comparisons between continuous interleaved sampling (CIS) and a
      temporal fine structure (TFS) coding strategy in Cantonese-speaking cochlear
      implant (CI) users did not reveal any significant differences in speech
      perception. Performance with the unfamiliar TFS coding strategy was on a par with
      CIS. Benefits of extended fine structure use observed in other studies should be
      investigated for tonal languages. OBJECTIVES: CIS-based stimulation strategies
      lack an explicit representation of fine structure, which is crucial for tonal
      language speech perception. The aim of this study was to assess speech
      recognition with a TFS coding strategy in Cantonese-speaking CI users with no
      prior fine structure experience. METHODS: The fine structure coding strategy
      encodes TFS on a few apical channels, while the remaining more basal channels
      carry CIS stimuli. Twelve MED-EL implantees and long-term CIS users participated
      in a study comparing recognition for Cantonese lexical tones and CHINT sentences
      between CIS and fine structure stimulation. RESULTS: Mean tone identification
      scores in 12 subjects were 59.2% with CIS and 59.2% with fine structure
      stimulation using 4 TFS channels, mean scores of CHINT sentences in 8 subjects
      were 54.2% with CIS and 55.9% with TFS stimulation. Differences between the two
      strategies were not significant for any speech test. Two additional versions of
      TFS strategy and pulse rates were tested in six subjects. No significant
      differences between strategies were found.

PMID- 20141489
TI  - Hearing and quality of life in a south European BAHA population.
AB  - CONCLUSION: The overall results show a high ratio of satisfaction in the sample
      population, which is in accordance with a successful BAHA counselling and
      rehabilitation of their hearing impairment. OBJECTIVES: The acceptance of a bone
      anchored hearing aid (BAHA) device by a south European population, which could be
      expected to have some reticence for wearing this device, has been investigated.
      METHODS: The outcome of BAHA implantation was assessed in 24 patients with
      bilateral and unilateral hearing loss by administration of several
      questionnaires, such as the Handicap Hearing Inventory (HHI), Client Oriented
      Scale of Improvement (COSI), Open and General Glasgow Benefit Inventory and
      Entific Medical System QoL, along with a complete audiological test battery.
      RESULTS: Speech reception threshold (SRT) in bilateral cases improved both in
      quiet and in noise. In unilateral cases, word perception and accuracy of sound
      localization improved when sound was presented from the back. COSI scores, at
      both the intermediate and the final evaluations, showed a fair adaptation level
      of the patients and their satisfaction for prefixed targets.

PMID- 20141490
TI  - Definite, probable, and possible bacterial aetiologies of community-acquired
      pneumonia at different CRB-65 scores.
AB  - According to the recommendations of the Swedish Community-Acquired Pneumonia
      (CAP) guidelines, the selection of empirical antibiotic therapy should be based
      on the CRB-65 rule. The guidelines recommend empirical therapy directed
      predominantly against Streptococcus pneumoniae for patients with low CRB-65
      scores and broad-spectrum therapy for patients with high CRB-65 scores. In order
      to study the utility of the recommendations, we analyzed the data from an
      aetiological study previously performed on 235 hospitalized adult CAP patients at
      our medical centre. A definite, probable, or possible bacterial aetiology was
      noted in 194 cases (83%), including 112 cases (48%) with S. pneumoniae aetiology.
      The following frequencies of definite-probable aetiologies were noted in the
      patients with CRB-65 score 0-1 (n=155) and CRB-65 score 2-4 (n=80): S. pneumoniae
      30% and 35%, Haemophilus influenzae 6.5% and 14% (p=0.063), Mycoplasma pneumoniae
      15% and 5.0% (p=0.019), Chlamydophila species 2.6% and 1.2%, Legionella
      pneumophila 1.9% and 0%, and Staphylococcus aureus 1.3% and 1.2%, respectively.
      The high frequency of S. pneumoniae in the study supports the recommendations to
      predominantly cover this bacterium in the empirical therapy of patients with low
      CRB-65 scores. In the case of treatment failure in these patients, the study
      indicates that coverage against M. pneumoniae and H. influenzae should be
      considered.

PMID- 20141491
TI  - Improving diagnostic criteria for Propionibacterium acnes osteomyelitis: a
      retrospective analysis.
AB  - The identification of Propionibacterium acnes in cultures of bone and joint
      samples is always difficult to interpret because of the ubiquity of this
      microorganism. The aim of this study was to propose a diagnostic strategy to
      distinguish infections from contaminations. This was a retrospective analysis of
      all patient charts of those patients with >or=1 deep samples culture-positive for
      P. acnes. Every criterion was tested for sensitivity, specificity, and positive
      likelihood ratio, and then the diagnostic probability of combinations of criteria
      was calculated. Among 65 patients, 52 (80%) were considered truly infected with
      P. acnes, a diagnosis based on a multidisciplinary process. The most valuable
      diagnostic criteria were: >or=2 positive deep samples, peri-operative findings
      (necrosis, hardware loosening, etc.), and >or=2 surgical procedures. However, no
      single criterion was sufficient to ascertain the diagnosis. The following
      combinations of criteria had a diagnostic probability of >90%: >or=2 positive
      cultures + 1 criterion among: peri-operative findings, local signs of infection,
      >or=2 previous operations, orthopaedic devices; 1 positive culture + 3 criteria
      among: peri-operative findings, local signs of infection, >or=2 previous surgical
      operations, orthopaedic devices, inflammatory syndrome. The diagnosis of P. acnes
      osteomyelitis was greatly improved by combining different criteria, allowing
      differentiation between infection and contamination.

PMID- 20141492
TI  - State-of-the-art of non-hormonal methods of contraception: IV. Natural family
      planning.
AB  - Despite the popularity of 'modern' contraceptives, natural family planning (NFP),
      including fertility awareness-based (FAB) methods and withdrawal, are practised
      in most countries. Worldwide FAB methods and withdrawal are used, respectively,
      by about 3.6% and 2.9% of all couples of reproductive age. This article describes
      the underpinnings of the different NFP methods, their rationales, histories,
      rules for use, efficacy and in broad categories their prevalence. Pregnancy rates
      of FAB methods with perfect use have ranged between 0.3 and 5.0 per 100 users per
      year, but typical use rates rises into the teens or higher. Withdrawal requires
      the male partner to be aware of his impending climax and to pull out of the
      vagina before ejaculation. Perfect use and typical pregnancy rates for withdrawal
      are estimated to be 4 and 27 per 100 per year, respectively. Many couples find
      NFP in accord with their own beliefs, satisfactory in its effectiveness and
      useful in planning a desired pregnancy. Many prize their self-control in
      practising NFP or withdrawal. In our research we used Medline, Popline and the
      Cochrane Library search engines in English, local institutional libraries, our
      own files in our native languages, the literature references contained therein,
      and source recommendations from colleagues.

PMID- 20141493
TI  - Energy expenditure of transfemoral amputees walking on a horizontal and tilted
      treadmill simulating different outdoor walking conditions.
AB  - Transfemoral amputees often report that walking on tilted pavements or on terrain
      with the prosthesis on the side of higher elevation is quite strenuous. This
      study investigates the energy expenditure of transfemoral amputees (n = 8) on a
      motorized treadmill, simulating different strenuous outdoor walking conditions.
      Oxygen uptake at self-selected speed of gait was measured during walking at three
      different treadmill positions: (i) Horizontal treadmill, (ii) 3% tilt in the
      sagittal plane and (iii) 3% tilt in both the sagittal and frontal plane of the
      treadmill. The difference in median values of oxygen uptake between position (i)
      and (ii) was 4.3%, and 16.4% between position (ii) and (iii) (p < or = 0.05, for
      both comparisons). The subjects utilized about 50% of their VO(2max) when walking
      in position (i) and (ii), with an increase to about 60% of their VO(2max) when
      walking in position (iii). Transfemoral amputees use significantly more energy
      when walking on a moderately tilted surface in the frontal plane compared to
      walking with a tilt in the sagittal plane. This is probably because the
      prosthetic leg becomes functionally too long when the walking surface is tilted
      sideways, and the transfemoral amputees adopt a more energy consuming gait
      pattern.

PMID- 20141494
TI  - The combined effect of Dynamic splinting and Neuromuscular electrical stimulation
      in reducing wrist and elbow contractures in six children with Cerebral palsy.
AB  - The aim of this pilot study was to investigate the feasibility of applying the
      combination of Dynamic splinting (DS) and Neuromuscular electrical stimulation
      (NMES) in order to improve wrist and elbow function, and range of motion, in
      children with upper limb contractures due to Cerebral palsy (CP). Six children
      aged seven to 16, with contractures at the wrist or elbow, were recruited.
      Following a 12-week baseline period all participants underwent a 12-week
      treatment period where DS was used for one hour per day and combined with NMES
      for the second half of the 1-h treatment. A 12-week follow-up period then ensued.
      Upper limb function was assessed with the Melbourne assessment, physical
      disability with the Paediatric Evaluation of Disability Index and the Activity
      Scale for Kids, and quality of life with the Pediatric Quality of Life Scale.
      Passive and active range of motion at the wrist and elbow were measured using
      manual and electrical goniometers. The technique of using combined NMES and DS
      was demonstrated to be feasible and compliance with the intervention was good.
      There was an increase in passive elbow extension in two participants treated for
      elbow contractures, although no accompanying change in upper limb function was
      demonstrated. Wrist range of movement improved in one participant treated for
      wrist contracture.

PMID- 20141495
TI  - The promise of glycomics, glycan arrays and carbohydrate-based vaccines.
AB  - Carbohydrates and glycoconjugates are involved in a number of biological
      processes including host-pathogen interactions, cell communication, proliferation
      and differentiation as well as the initiation of immune responses. However,
      access to synthetic oligosaccharide structures has been limited for long time
      since no standardized protocols for the synthesis of complex oligosaccharides
      from monomeric building block existed. Recent advances in glycochemistry and
      glycobiology have helped elucidate biological functions of carbohydrates. Novel
      methods such as automated synthesis of vaccine candidates and immunologically
      relevant carbohydrates have contributed to this success as well as high
      throughput methods such as glycan arrays. This review illustrates the impact of
      carbohydrate synthesis on the design of efficient carbohydrate-based
      antimicrobial and anticancer vaccines. Furthermore, this review focuses on how
      immunological research can benefit from these novel tools provided by
      glycochemistry.

PMID- 20141496
TI  - Routine outcome measurement in mental health: feasibility for examining
      effectiveness of an NGO.
AB  - OBJECTIVE: The aim of this study was to examine the feasibility of using routine
      public mental health outcome data to measure the effectiveness of a non
      government organization (NGO), specifically Pioneer Clubhouse. METHOD: We
      retrieved data from the NSW Mental Health Outcomes and Assessment Tools (MH-OAT)
      database, for 31 participants who joined Pioneer Clubhouse, NSW, in 2007. Data
      were also sought for 31 matched control participants from within the same Area
      Health Service. Data collected from the adult MH-OAT instruments, Health of the
      Nation Outcome Scales (HoNOS), Kessler-10 (K-10) and Abbreviated Life Skills
      Profile-16 (LSP-16), was retrieved for 13 weeks prior to joining date and
      compared with 13 weeks of data 6 months after joining. RESULTS: Twenty-four
      Clubhouse members were registered in the MH-OAT database. Only one of the 24
      participants had data for both time periods requested. MH-OAT data collection was
      insufficient to allow their use for measuring effectiveness of a NGO. CONCLUSION:
      Despite the National Mental Health Plan emphasis, and extensive and expensive
      support for routine data collection in public mental health services, such data
      collection has been unsuccessful. We discuss possible reasons for this.

PMID- 20141497
TI  - Public interest and private concern: the role of family carers for people
      suffering mental illness in the twenty first century.
AB  - OBJECTIVES: This paper looks to examine the emerging role of carers as essential
      components in the management of individuals affected by severe mental illness in
      the context of modern legal and health policy environments. CONCLUSIONS: Cultural
      and legal concepts of confidentiality within the doctor-patient relationship are
      complex. Increasingly, evidence is recognizing the essential role of carers in
      the quality management of individuals affected by severe mental illness and this
      emphasis is being further supported by innovative health policy and legislation.
      A public health definition for the role of carers may be a more appropriate way
      to consider their role in mental health management strategies.

PMID- 20141498
TI  - Transdermal nortriptyline hydrocloride patch formulated within a chitosan matrix
      intended to be used for smoking cessation.
AB  - OBJECTIVE: The aim of this study was to prepare and characterize both physically
      and biopharmaceutically, a nortriptyline hydrochloride (NTP-HCl) patch formulated
      in chitosan. METHODS: 16 g of each chitosan patch formulation (I, II and III, see
      Table 1 ) was poured onto rectangular glass plates (64 cm2) at a height of 1 mm
      and dried for 24 h at room temperature. In order to characterize the chitosan
      patches, polarized microscopy, in vitro skin permeation studies by passive
      diffusion and iontophoresis and rheological and bioadhesion studies were
      performed. RESULTS: Polarized microscopy revealed the absence of aggregates and
      crystal forms of NTP-HCl in all transdermal patches after 30 days of storage. The
      rheological behavior of Patches I, II and III was predominantly elastic. The low
      level of adhesion of Patch III (containing PF-127 + 1-dodecanol) could be a
      result of the interactions between chitosan and PF-127 in the presence of 1
      dodecanol. Patches I and II had approximately the same value of adhesion (~ 60
      mN.mm). The transdermal patch with chitosan, PF-127 and 1-dodecanol (Patch III)
      provided a reasonable flux of NTP-HCl across the skin compared with Patches I and
      II. Iontophoresis applied to the patches did not increase the penetration of NTP
      HCl across the skin. CONCLUSIONS: The data suggest that Patch III is suitable for
      use in clinical practice pending further studies.

PMID- 20141499
TI  - Measurement of lymph node function from the extraction of immunoglobulin in
      lymph.
AB  - BACKGROUND: We aimed to measure the extraction fraction of human immunoglobulin G
      (HIG) by the 1st echelon lymph node (sentinel node) following intradermal
      injection in patients with breast cancer undergoing axillary lymph node
      dissection (ALND) and examine its association with node size and presence and
      extent of nodal metastatic disease. MATERIALS AND METHODS: HIG labelled with
      either In-111 (n = 21) or Tc-99m (n = 9) was injected intradermally at the
      areolar. ALND was performed 2-4 h later. All lymph nodes were isolated and
      individually counted in a well-counter. The counts in the 'hottest' (1st echelon)
      node were expressed as a fraction of total counts in all the resected nodes.
      Since counts in the least hot nodes barely exceeded background, this fraction
      represents extraction fraction for the 1st echelon node. Presence of disease was
      noted in each 1st echelon node and the extent quantified as percentage
      replacement with disease. RESULTS: Median extraction fraction in 1st echelon
      nodes with no or low (<1%) disease burden (n = 21) was 68 (range 23-93)%,
      significantly higher (p < 0.05) than in diseased 1st echelon nodes (n = 9), in
      which it was 44 (21-66)%. There was, however, no association between extraction
      fraction in diseased nodes and disease extent. In nodes with no/low disease,
      extraction fraction was similar for the two radiolabels. There was no association
      between extraction fraction and node size. CONCLUSION: Nodal extraction fraction
      of HIG is a novel physiological measurement. It is reduced as a result of
      metastatic invasion. In the absence of disease, it shows no correlation with node
      size.

PMID- 20141501
TI  - Preparation and standardization of a herbal agent for the therapeutic management
      of asthma.
AB  - This study aims to develop a suitable single tablet dosage form containing a
      mixture of hot water stem back extracts of Anogeissus leiocarpus and Prosopis
      africana (AA1), suitable for use in the therapeutic management of asthma. The
      compaction characteristics of the oven-dried hot water extract (HWE) were studied
      using the Heckel equation. The mechanical properties as well as disintegration
      and dissolution profile of the compacts were also assessed. The results showed
      that AA1 exhibited high densification due to dye filling while the subsequent
      rearrangement of the granules did not contribute, significantly, to their
      densification. The granules had enhanced plasticity as shown by the low yield
      point, Py. The tablets produced from the extract had good mechanical properties,
      with hardness increasing with compression pressure while the friability
      decreased. Of the four disintegrants tested, tablets containing Explotab had the
      shortest disintegration time of 11 min while tablets containing Prosolv had the
      longest disintegration time of 40 min. The order of disintegrant property is
      Explotab > Cellactose > Emcocel > Maize starch > Prosolv. Dissolution results
      (t(90%)) show that tablets containing Explotab released 100% of the drug in 20
      min proving to be the most suitable in acute asthma attack. The order of
      dissolution is Explotab > Cellactose > Maize starch > Prosolv > Emcocel. It is
      concluded that incorporation of Explotab (10%w/w) as a disintegrant in AA1
      preparation produced tablets of suitable compressional properties and ensured
      adequate drug release for the management of acute asthma.

PMID- 20141500
TI  - Tumor necrosis factor-alpha acutely up-regulates urea synthesis in vivo in rats-
      a hepatic component of inflammatory catabolism?
AB  - BACKGROUND: Catabolism is a serious problem in patients with active inflammation.
      The tissue nitrogen (N) depletion is related to increased hepatic capacity for
      elimination of N via conversion of amino-N into urea-N. This is caused by the
      inflammatory process, but the mediators responsible are unknown. Tumor necrosis
      factor-alpha (TNF-alpha) plays a key role in inflammation, and we hypothesized
      that TNF-alpha up-regulates urea synthesis. METHODS: We examined the in vivo
      capacity of urea-N synthesis (CUNS) and mRNA levels of urea cycle enzyme genes 3
      h after TNF-alpha injection in rats. Circulating concentrations of glucagon,
      corticosterone, insulin, glucose, cytokines and acute phase proteins and their
      liver tissue gene expressions were measured. RESULTS: TNF-alpha increased CUNS by
      40% (p=0.03) despite decreased urea-cycle enzyme gene expression. TNF-alpha
      increased interleukin 6 (IL-6) (p < 0.001); circulating acute phase proteins were
      unchanged. CONCLUSION: TNF-alpha in rats caused an acute up-regulation of the in
      vivo capacity of urea synthesis which may promote loss of nitrogen from the body
      and catabolism. The results indicate that TNF-alpha has a post-transcriptional
      effect on regulation of urea synthesis that is independent of the acute phase
      protein synthesis. Effects of IL-6 may be involved.

PMID- 20141502
TI  - Evaluation and modeling of the eutectic composition of various drug-polyethylene
      glycol solid dispersions.
AB  - The purpose of this study was to gain a better understanding of which factors
      contribute to the eutectic composition of drug-polyethylene glycol (PEG) blends
      and to compare experimental values with predictions from the semi-empirical model
      developed by Lacoulonche et al. Eutectic compositions of various drug-PEG 3350
      solid dispersions were predicted, assuming athermal mixing, and compared to
      experimentally determined eutectic points. The presence or absence of specific
      interactions between the drug and PEG 3350 were investigated using Fourier
      transform infrared (FT-IR) spectroscopy. The eutectic composition for haloperidol
      PEG and loratadine-PEG solid dispersions was accurately predicted using the
      model, while predictions for aceclofenac-PEG and chlorpropamide-PEG were very
      different from those experimentally observed. Deviations in the model prediction
      from ideal behavior for the systems evaluated were confirmed to be due to the
      presence of specific interactions between the drug and polymer, as demonstrated
      by IR spectroscopy. Detailed analysis showed that the eutectic composition
      prediction from the model is interdependent on the crystal lattice energy of the
      drug compound (evaluated from the melting temperature and the heat of fusion) as
      well as the nature of the drug-polymer interactions. In conclusion, for compounds
      with melting points less than 200 degrees C, the model is ideally suited for
      predicting the eutectic composition of systems where there is an absence of drug
      polymer interactions.

PMID- 20141504
TI  - Annotated patent selections.

PMID- 20141503
TI  - VEGF receptor kinase inhibitors: phthalazines, anthranilamides and related
      structures.
AB  - Inhibition of vascular endothelial growth factor receptor (VEGFR) signalling,
      using either antibodies or small molecule inhibitors of the VEGFR kinase domain,
      has become a major area of research in oncology. The phthalazine PTK787/ZK222584,
      first published in the literature in 1998, is one of the most advanced VEGFR
      inhibitors in the clinic. This paper provides an update on the patenting activity
      related to the phthalazine class. In addition, newer kinase inhibitor
      pharmacophores derived from this class (e.g., anthranilamides) will be reviewed.

PMID- 20141505
TI  - Isoforms of human B7-H3 co-signalling molecule for T cell activation as potential
      immunoregulatory agents.
AB  - B7 family molecules, which are expressed on antigen-presenting cells and display
      extracellular regions containing immunoglobulin (Ig) variable (V)- and constant
      (C)-like domains, are known to modulate T cell receptor (TCR)-mediated T cell
      activation by providing co-signals that are either stimulatory or inhibitory. One
      of the most recently identified members of this family is B7-H3 (B7 homologue 3).
      Here, evidence is presented that human B7-H3 exists as two isoforms: B7-H3 VC,
      which contains one IgV- and IgC-like domain, and B7-H3 VCVC, which contains two
      such domains. The latter represents the predominant B7-H3 molecule detectable in
      various human tissues. Both B7-H3 isoforms are shown to decrease the
      proliferation and cytokine production induced by TCR activation of human T cells
      in vitro. It is therefore claimed that B7-H3 molecules may provide tools to
      modulate immune responses for therapeutic purpose.

PMID- 20141506
TI  - Novel pH-sensitive hydrogels for colon-specific drug delivery.
AB  - The purpose of this study is to develop novel intestinal specific drug delivery
      systems with pH-sensitive swelling and drug release properties. Acryloyl ester of
      5-[4-(hydroxy phenyl) azo] salicylic acid (HPAS) as an azo derivative of 5-amino
      salicylic acid (5-ASA) was prepared under mild conditions. The HPAS was
      covalently linked with acryloyl chloride, abbreviated as APAS. Cubane-1,4
      dicarboxylic acid (CDA), linked to two 2-hydroxyethyl methacrylate (HEMA) groups,
      was the cross-linking agent (CA). Methacrylic-type polymeric prodrugs were
      synthesized by free radical copolymerization of methacrylic acid,
      poly(ethyleneglycol monomethyl ether methacrylate), and APAS in the presence of
      cubane cross-linking agent. The effect of copolymer composition on the swelling
      behavior and hydrolytic degradation were studied in simulated gastric (SGF, pH 1)
      and intestinal fluids (SIF, pH 7.4). The composition of the cross-linked three
      dimensional polymers was determined by FTIR spectroscopy. The hydrolysis of drug
      polymer conjugates was carried out in cellophane membrane dialysis bags
      containing aqueous buffer solutions (pH 1 and pH 7.4) at 37 degrees C. Detection
      of the hydrolysis product by UV spectroscopy shows that the azo prodrug (HPAS)
      was released by hydrolysis of the ester bond located between the HPAS and the
      polymer chain. Drug release studies showed that the increasing content of MAA in
      the copolymer enhances hydrolysis in SIF. These results suggest that pH-sensitive
      systems could be useful for preparation of a muccoadhesive system and controlled
      release of HPAS as an azo derivative of 5-amino salicylic acid (5-ASA).

PMID- 20141507
TI  - Emerging approaches to the treatment of uveitis: patents of 2000 - 2004.
AB  - The treatment of non-infectious uveitis is often a challenging experience for
      both the patient and the treating physician. The use of traditional forms of
      treatment is restricted by limited effectiveness and considerable side effects.
      This review examines the current trends in therapy and the emerging new classes
      of therapeutic agents used in the treatment of non-infectious uveitis. It then
      examines some of the newer approaches apparent from recent patenting over the
      past four years and assesses their likely future significance.

PMID- 20141508
TI  - The sulfamide motif in the design of enzyme inhibitors.
AB  - The sulfamide moiety, similarly to the structurally related sulfonamide and
      sulfamate ones, is widely employed in medicinal chemistry for the design of
      biologically active compounds. Amongst the enzymes for which sulfamide-based
      inhibitors were designed are the carbonic anhydrases (CAs), and a large number of
      proteases belonging to the aspartic protease (HIV-1 protease, gamma-secretase),
      serine protease (elastase, chymase, tryptase and thrombin, among others) and
      metalloproteinase (carboxypeptidase A [CPA] and matrix metalloproteinase [MMP])
      families. Some steroid sulfatase (STS) and protein tyrosine phosphatase
      inhibitors belonging to the sulfamide class of derivatives have also been
      reported. In all these compounds, many of which show low nanomolar affinity for
      the target enzymes for which they have been designed, the free or substituted
      sulfamide moiety plays an important role in the binding of the inhibitor to the
      active site cavity. This is achieved either by directly coordinating to the metal
      ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the
      nitrogen atoms present in the sulfamide motif, or, as in the case of the cyclic
      sulfamides, acting as HIV protease inhibitors interacting with the catalytically
      critical aspartic acid residues of the active site by means of an oxygen atom
      belonging to the HN-SO(2)-NH motif that substitutes a catalytically essential
      water molecule. In other cases, the sulfamide moiety is important for inducing
      desired physicochemical properties to the drug-like compounds incorporating it,
      such as enhanced water solubility, better bioavailability etc., due to the
      intrinsic properties of this highly polarised moiety when attached to an organic
      scaffold. This interesting motif is, thus, of great value for the design of
      pharmacological agents with many applications.

PMID- 20141509
TI  - Long-acting beta2 agonists.
AB  - Two applications claim very closely related arylsulfonamide beta(2)-agonists. The
      basic generic claim is the same in both cases with subsidiary claims covering
      different permutations of the same Markush structure. The claimed compounds are
      potent beta(2)-agonists whose structures suggest that they would have a long
      duration of action. These applications represent part of what is now a
      significant chemical programme at Pfizer.

PMID- 20141510
TI  - Patented small molecule inhibitors of p53-MDM2 interaction.
AB  - The interaction between p53 and murine double minute 2 (MDM2) provides an
      attractive drug target in oncology. Small molecule inhibitors of this interaction
      have not only provided strong evidence for blocking the protein-protein
      interaction, but are also extremely useful as biological probes and ultimately as
      novel therapeutics. Here, a comprehensive review of the patented small molecule
      inhibitors of the p53-MDM2 interaction are provided. These inhibitors are divided
      into eight classes of compounds that include cis-imidazolines, benzodiazepines,
      fused indoles, substituted piperazines, substituted piperidines, aryl boronic
      acids, spiro-indoles, and alpha-helix mimetic compounds. The best documented
      class of compounds, cis-imidazolines (e.g., Nutlins) are selective and potent
      inhibitors of the p53-MDM2 interaction, and selected examples exhibit potency in
      the nanomolar range. Nutlins induce apoptosis in p53 wild-type cells and show in
      vivo efficacy in mice xenograft models. Additional strategies briefly discussed
      in this review, and which are under current exploration in targeting the p53
      pathway, include the inhibition of MDM2-mediated p53 ubiquitylation and
      restoration of DNA-binding activity of mutant p53 protein using small molecules.

PMID- 20141512
TI  - Frataxin, a molecule of mystery: trading stability for function in its iron
      binding site.
AB  - What are the structural implications for iron binding by frataxin, the
      mitochondrial protein whose decreased expression results in Friedreich's ataxia?
      Though frataxin has been shown to be essential for proper handling of iron within
      mitochondria (e.g. for iron-sulfur cluster and haem biosynthesis), its exact
      molecular function remains unclear. In this issue of the Biochemical Journal,
      Correia and colleagues. investigate the relationship between structure and
      function at the putative iron-binding site of Yfh1 (yeast frataxin). Using a host
      of Yfh1 combination point mutants, the authors observe that the presence of a
      semi-conserved pocket of negative charge within the 'acidic ridge' region
      (thought to be responsible for iron binding) only mildly enhances Yfh1's ability
      to bind iron, though it does significantly increase the protein's structural
      flexibility. The general emerging view is that frataxin's keystone role in
      mitochondrial iron metabolism depends on iron binding. This appears to have
      downstream effects on protein-protein interactions that are crucial for frataxin
      function. The current results reveal a somewhat delicate relationship between
      iron binding and structural plasticity that may help unravel the enigma of
      frataxin's metabolic roles.

PMID- 20141511
TI  - Bioinformatic and experimental survey of 14-3-3-binding sites.
AB  - More than 200 phosphorylated 14-3-3-binding sites in the literature were analysed
      to define 14-3-3 specificities, identify relevant protein kinases, and give
      insights into how cellular 14-3-3/phosphoprotein networks work. Mode I
      RXX(pS/pT)XP motifs dominate, although the +2 proline residue occurs in less than
      half, and LX(R/K)SX(pS/pT)XP is prominent in plant 14-3-3-binding sites. Proline
      at +1 is rarely reported, and such motifs did not stand up to experimental
      reanalysis of human Ndel1. Instead, we discovered that 14-3-3 interacts with two
      residues that are phosphorylated by basophilic kinases and located in the DISC1
      (disrupted-in-schizophrenia 1)-interacting region of Ndel1 that is implicated in
      cognitive disorders. These data conform with the general findings that there are
      different subtypes of 14-3-3-binding sites that overlap with the specificities of
      different basophilic AGC (protein kinase A/protein kinase G/protein kinase C
      family) and CaMK (Ca2+/calmodulin-dependent protein kinase) protein kinases, and
      a 14-3-3 dimer often engages with two tandem phosphorylated sites, which is a
      configuration with special signalling, mechanical and evolutionary properties.
      Thus 14-3-3 dimers can be digital logic gates that integrate more than one input
      to generate an action, and coincidence detectors when the two binding sites are
      phosphorylated by different protein kinases. Paired sites are generally located
      within disordered regions and/or straddle either side of functional domains,
      indicating how 14-3-3 dimers modulate the conformations and/or interactions of
      their targets. Finally, 14-3-3 proteins bind to members of several multi-protein
      families. Two 14-3-3-binding sites are conserved across the class IIa histone
      deacetylases, whereas other protein families display differential regulation by
      14-3-3s. We speculate that 14-3-3 dimers may have contributed to the evolution of
      such families, tailoring regulatory inputs to different physiological demands.

PMID- 20141513
TI  - Reflections on studies of gene expression in aneuploids.
AB  - Aneuploidy involves changes in chromosomal copy number compared with normal
      euploid genotypes. Studies of gene expression in aneuploids in a variety of
      species have claimed many different types of responses. Studies of individual
      genes suggest that there are both structural gene dosage effects and compensation
      in aneuploids, and that subtle trans-acting effects across the genome are quite
      prevalent. A discussion is presented concerning the normalization procedures for
      studying gene expression in aneuploids. A careful documentation of the
      modulations of gene expression in aneuploids should provide insight into the
      nature of cancerous cells and the basis of aneuploid syndromes.

PMID- 20141514
TI  - 2010 re-launch of BJP.

PMID- 20141515
TI  - Reducing QT liability and proarrhythmic risk in drug discovery and development.
AB  - Drug-induced torsades de pointes (TdP), a rare, life-threatening, polymorphic,
      ventricular tachycardia associated with prolongation of the QT interval, has been
      the main safety reason for the withdrawal of medicines from clinical use over the
      last decade. Most often, drugs that prolong the action potential and delay
      ventricular repolarization do so through blockade of outward (repolarizing)
      currents, predominantly the rapid delayed rectifying potassium current, I(Kr).
      While QT interval prolongation is not a safety concern per se, in a small
      percentage of people, it has been associated with TdP, which either spontaneously
      terminates or degenerates into ventricular fibrillation. Furthermore, recent data
      suggest that shortening of the QT interval may also be a new safety issue waiting
      to surface. This review article summarizes the presentations given at a symposium
      entitled 'Reducing QT liability and proarrhythmic risk in drug discovery and
      development', which was part of the Federation of the European Pharmacological
      Societies congress, Manchester, UK, 13-17 July 2008. The objective of this
      symposium was to assess the effects of implementing the latest regulatory
      guidance documents (International Conference on Harmonization S7A/B and E14), as
      well as new scientific and technical trends on the ability of the pharmaceutical
      industry to reduce and manage the QT liability and associated potential
      proarrhythmic risk, and contribute to the discovery and development of safer
      medicines. This review outlines the key messages from communications presented at
      this symposium and attempts to highlight some of the key challenges that remain
      to be addressed.

PMID- 20141516
TI  - An introduction to QT interval prolongation and non-clinical approaches to
      assessing and reducing risk.
AB  - Owing to its association with Torsades de Pointes, drug-induced QT interval
      prolongation has been and remains a significant hurdle to the development of
      safe, effective medicines. Genetic and pharmacological evidence highlighting the
      pivotal role the human ether-a-go-go-related gene (hERG) channel was a critical
      step in understanding how to start addressing this issue. It led to the
      development of hERG assays with the rapid throughput needed for the short
      timescales required in early drug discovery. The resulting volume of hERG data
      has fostered in silico models to help chemists design compounds with reduced hERG
      potency. In early drug discovery, a pragmatic approach based on exceeding a given
      potency value has been required to decide when a compound is likely to carry a
      low QT risk, to support its progression to late-stage discovery. At this point,
      the in vivo efficacy and metabolism characteristics of the potential drug are
      generally defined, as well its safety profile, which includes usually a dog study
      to assess QT interval prolongation risk. The hERG and in vivo QT data, combined
      with the likely indication and the estimated free drug level for efficacy, are
      put together to assess the risk that the potential drug will prolong QT in man.
      Further data may be required to refine the risk assessment before making the
      major investment decisions for full development. The non-clinical data are
      essential to inform decisions about compound progression and to optimize the
      design of clinical QT studies.

PMID- 20141517
TI  - Dealing with hERG liabilities early: diverse approaches to an important goal in
      drug development.

PMID- 20141518
TI  - Value of non-clinical cardiac repolarization assays in supporting the discovery
      and development of safer medicines.
AB  - Non-clinical QT-related assays aligned to the pharmaceutical drug discovery and
      development phases are used in several ways. During the early discovery phases,
      assays are used for hazard identification and wherever possible for hazard
      elimination. The data generated enable us to: (i) establish structure-activity
      relationships and thereby; (ii) influence the medicinal chemistry design and
      provide tools for effective decision making; and provide structure-activity data
      for in silico predictive databases; (iii) solve problems earlier; (iv) provide
      reassurance for compound or project to progress; and (v) refine strategies as
      scientific and technical knowledge grows. For compounds progressing into pre
      clinical development, the 'core battery' QT-related data enable an integrated
      risk assessment to: (i) fulfil regulatory requirements; (ii) assess the safety
      and risk-benefit for compound progression to man; (iii) contribute to defining
      the starting dose during the phase I clinical trials; (iv) influence the design
      of the phase I clinical trials; (v) identify clinically relevant safety
      biomarkers; and (vi) contribute to the patient risk management plan. Once a
      compound progresses into clinical development, QT-related data can be applied in
      the context of risk management and risk mitigation. The data from 'follow-up'
      studies can be used to: (i) support regulatory approval; (ii) investigate
      discrepancies that may have emerged within and/or between non-clinical and
      clinical data; (iii) understand the mechanism of an undesirable pharmacodynamic
      effect; (iv) provide reassurance for progression into multiple dosing in humans
      and/or large-scale clinical trials; and (v) assess drug-drug interactions. Based
      on emerging data, the integrated risk assessment is then reviewed in this
      article, and the benefit-risk for compound progression was re-assessed. Project
      examples are provided to illustrate the impact of non-clinical data to support
      compound progression throughout the drug discovery and development phases, and
      regulatory approval.

PMID- 20141520
TI  - Pulmonary oedema in healthy SCUBA divers: new physiopathological pathways.
AB  - INTRODUCTION: The mechanism of immersion pulmonary oedema occurring in healthy
      divers is a matter of debate. Among consecutive injured divers admitted to our
      hyperbaric centre, we analysed prospective data about pulmonary oedema. METHOD: A
      total of 22 divers suffering from immersion pulmonary oedema without cardiac
      disease were included. The occurrence of events was compared to the diving
      conditions as assessed by diving-computer. Each patient underwent a clinical
      examination, laboratory tests, thoracic CT scan and echocardiography. RESULTS:
      The median age was 49 years, with a higher proportion of women, in comparison
      with the data of the French diving federation. The common feature was the
      occurrence of respiratory symptoms during the ascent after median dive duration
      of 29 min with strenuous exercise and/or psychological stress. Most of the dives
      were deep (37 msw-121 fsw) in cool water (15 degrees C-59 degrees F). The average
      inspired oxygen partial pressure was 0.99 bar. Progression was rapidly
      favourable, and the medical check-up after clinical recovery was normal.
      CONCLUSION: Immersion, body cooling, hyperoxia, increased hydrostatic pressure
      and strenuous exercise likely combine to induce pulmonary oedema in patients
      without cardiac disease. This study underlines new physiopathological tracks
      related to the frequent occurrence of symptoms noticed in the last part of the
      ascent and a higher incidence in women.

PMID- 20141519
TI  - Facts, fancies and follies of drug-induced QT/QTc interval shortening.

PMID- 20141521
TI  - Drug management in emergent liver transplantation of mitochondrial disorder
      carriers: review of the literature.
AB  - BACKGROUND: Mitochondrial respiratory-chain disorders (MRCD) lead to progressive
      disabling of neurological and cellular conditions that involve muscles, brain,
      kidney, and liver dysfunction. Affected individuals may need surgery, including
      orthotopic liver transplantation (OLT). Surgery poses anesthesia challenges
      because of the prolonged use of anesthetic drugs and sedatives, which may inhibit
      oxidative phosphorylation, mimic mitochondrial cytopathic disorders, or unveil
      them ex novo. MATERIALS AND METHODS: We conducted a multilingual PubMed search of
      surgical and non-surgical anesthesia reports between the years 1992 and 2008,
      where anesthetic drugs were used in MRCD patients, especially for those
      undergoing urgent OLTs. RESULTS: There were 51 case reports of 210 anesthesia and
      critical care interventions in patients with MRCD, a large part of them were
      children. Data pertaining to the safe usage of anesthesia and perioperative drugs
      were limited and conflicting. We found no article that addressed the issue of
      perioperative handling of urgent OLT in MRCD patients. We therefore suggest our
      own - although limited - experience for such occasions. CONCLUSION: There are no
      randomized, controlled, trial-based indications regarding safe anesthetic drugs
      to be used perioperatively in MRCD carriers. Consultation among geneticists,
      anesthesiologists, intensivists, and surgeons is essential in patients with
      known/suspected metabolic syndrome for planning appropriate perioperative care.

PMID- 20141522
TI  - Fracture resistance and reinforcement of immature roots with gutta percha,
      mineral trioxide aggregate and calcium phosphate bone cement: a standardized in
      vitro model.
AB  - Endodontic treatment of immature teeth is often complicated because of flaring
      root canals and open apices for which apexification is needed. Long-term
      prognosis for these teeth is surprisingly low because of cervical root fractures
      occurring after an impact of weak forces. In this study, an experimental model
      was developed to determine the fracture resistance of immature teeth and to test
      the hypothesis that endodontic materials succeed in reinforcing them. Compact and
      hollow bone cylinders from bovine femurs were used as standardized samples. In
      order to evaluate the experimental model, fracture resistance in both groups was
      evaluated by determining the ultimate force to fracture (UFF) under diametral
      tensile stress. Analysis of variance (ANOVA) revealed a statistically significant
      difference between the mean values of UFF for both groups, independently of the
      sampling location or subject. In a following setting, the hypothesis that
      obturation with gutta percha (GP), mineral trioxide aggregate (MTA), or calcium
      phosphate bone cement (CPBC) reinforces the hollow bone samples was investigated.
      Obturation resulted in a significant reinforcement for all materials, but the
      degree of reinforcement depended on the material. The experimental model appeared
      to be suitable for in vitro investigation of reinforcement and fracture
      resistance in a standardized way.

PMID- 20141523
TI  - Understanding school teacher's knowledge regarding dental trauma: a basis for
      future interventions.
AB  - BACKGROUND: Traumatic dental injuries frequently occur at school environment.
      However, teachers are not prepared to provide the adequate emergency management.
      AIM: The objectives of this study were to identify the factors associated with
      teachers' knowledge about dental trauma and to describe school managers'
      perception of possible strategies to change the scenario. SUBJECTS AND METHODS:
      Our sample comprised 405 teachers from 17 public schools in Canoas, state of Rio
      Grande do Sul, Brazil, whose data were collected regarding demographic variables,
      training and professional experience information. The outcome was completely
      inadequate knowledge regarding trauma measured based on the answers to a
      structured questionnaire about dental fractures and tooth avulsion. The sample
      also included 14 school managers who answered a semi-structured questionnaire
      about the causes of teachers' inadequate knowledge and possible strategies to
      change the scenario. RESULTS: The multivariate analysis demonstrated that the
      probability of completely inadequate knowledge was higher among male teachers,
      with less professional experience, who had not achieved a graduate degree, who
      had not witnessed at least one dental trauma case at school and who had not been
      trained in first-aid. School managers identified the following causes of
      inadequate knowledge: the fact that the topic is not approached during the
      teachers' training and continual education and lack of experience involving
      dental trauma at school. In addition, they suggested that lectures and courses
      including written and visual communication should be offered, as well as training
      workshops. CONCLUSIONS: Strategies to improve the teachers' knowledge about
      dental trauma must take into consideration the results of the present study and
      optimize the inclusion of this topic in the teachers' curricular training and
      pedagogical education in a continuous manner.

PMID- 20141524
TI  - Assessment of traumatic injuries to primary teeth in general practise and
      specialized paediatric dentistry.
AB  - AIM: The aim of this prospective study was to compare diagnosis, severity of
      trauma and treatment of traumatic injuries to the primary dentition in two groups
      of children, the first recommended for treatment by general practitioners and the
      second referred for treatment by a specialist paediatric dentist. MATERIALS AND
      METHODS: A total of 323 children with traumatic injuries, 184 boys and 139 girls
      aged 7-83 months, participated in the study. All the children had first presented
      at a Public Dental Service clinic where they were examined by general dentists
      who decided, based on the severity of the trauma, to assign each child to one of
      the following two groups: Group A--recommended for treatment at the general
      practise (166 children with 257 traumatized incisor teeth). Group B--recommended
      for referral to a specialist in paediatric dentistry (157 children with 261
      traumatized incisor teeth). Even in Group A, the specialist controlled the
      treatment decisions. The clinical diagnose and follow-up followed the
      recommendations presented by Andreasen & Andreasen. RESULTS: The distribution of
      trauma by age was similar in both groups, with about 60% occurring between 1 and
      3 years. More injured teeth were extracted in children in Group B (n = 111) than
      in Group A (n = 33). A higher percentage of intruded primary incisors were
      recorded in Group B (24%) compared with Group A (16%). Similarly, the percentage
      of concussions/subluxations, lateral luxations and complicated crown fractures
      was higher in Group B than in Group A. CONCLUSIONS: The group referred for
      specialist treatment had more severe injuries and needed more complicated
      treatment than the group recommended for care by general dentists. However, the
      rate of sequelae in permanent successors was the same in both.

PMID- 20141525
TI  - Global marine primary production constrains fisheries catches.
AB  - Primary production must constrain the amount of fish and invertebrates available
      to expanding fisheries; however the degree of limitation has only been
      demonstrated at regional scales to date. Here we show that phytoplanktonic
      primary production, estimated from an ocean-colour satellite (SeaWiFS), is
      related to global fisheries catches at the scale of Large Marine Ecosystems,
      while accounting for temperature and ecological factors such as ecosystem size
      and type, species richness, animal body size, and the degree and nature of
      fisheries exploitation. Indeed we show that global fisheries catches since 1950
      have been increasingly constrained by the amount of primary production. The
      primary production appropriated by current global fisheries is 17-112% higher
      than that appropriated by sustainable fisheries. Global primary production
      appears to be declining, in some part due to climate variability and change, with
      consequences for the near future fisheries catches.

PMID- 20141526
TI  - Evolution of resistance to the Bacillus sphaericus Bin toxin is phenotypically
      masked by combination with the mosquitocidal proteins of Bacillus thuringiensis
      subspecies israelensis.
AB  - Two insecticidal bacteria are used as larvicides to control larvae of nuisance
      and vector mosquitoes in many countries, Bacillus thuringiensis ssp. israelensis
      and B. sphaericus. Field studies show both are effective, but serious resistance,
      as high as 50 000-fold, has evolved where B. sphaericus is used against Culex
      mosquitoes. To improve efficacy and deal with even greater potential problems of
      resistance, we previously developed several recombinant larvicidal bacteria that
      combine the best mosquitocidal proteins of these bacteria. In the present study,
      we report laboratory selection studies using our best recombinant strain against
      larvae of Culex quinquefasciatus. This recombinant, Bti/BsBin, is a strain of B.
      thuringiensis ssp. israelensis engineered to produce a large amount of the B.
      sphaericus binary (Bin) toxin, which makes it more than 10-fold as mosquitocidal
      as the its parental strains. Here we show that larvae exposed to Bti/BsBin failed
      to develop significant resistance after 30 successive generations of heavy
      selection pressure. The highest level of resistance obtained at the LC(95) level
      was 5.2-fold, but declined to less than two-fold at the 35th generation. Testing
      the selected populations against B. sphaericus alone showed resistance to Bin
      evolved, but was masked by combination with B. thuringiensis ssp. israelensis.
      These results suggest that recombinant bacterial strains have improved mosquito
      and vector management properties compared with the wild-type strains used in
      current commercial formulations, and should prove useful in controlling important
      human diseases such as malaria and filariasis on a long-term basis, even when
      used intensively under field conditions.

PMID- 20141527
TI  - The role of the dopamine transporter DAT1 genotype on the neural correlates of
      cognitive flexibility.
AB  - Cognitive flexibility, the ability to adapt goal-oriented behaviour in response
      to changing environmental demands, varies widely amongst individuals, yet its
      underlying neural mechanisms are not fully understood. Neuropharmacological and
      human clinical studies have suggested a critical role for striatal dopaminergic
      function mediated by the dopamine transporter (DAT). The present study aimed at
      revealing the role of the DAT in the individual brain response stereotypy
      underlying cognitive flexibility. A task-switching protocol was administered to a
      sample divided according to the presence or absence of the 9-repeat (9R) allele
      of the DAT1 polymorphism, while registering behavioural and electrophysiological
      novelty-P3 responses. The absence of the 9R (higher gene expression) is related
      to less striatal DA availability. Individuals lacking the 9R (9R-) showed
      specific response time (RT) increases for sensory change and task-set
      reconfiguration, as well as brain modulations not observed in participants with
      the 9R allele (9R+), suggesting that task performance of the former group
      depended on immediate local context. In contrast, individuals displaying high
      striatal DA showed larger RT costs than 9R- individuals to any sensory change,
      with no further increase for task-set reconfiguration, and a larger early
      positive brain response irrespective of the task condition, probably reflecting
      larger inhibition of any previous interference as well as stronger activation of
      the current task set. However, the polymorphic groups did not differ in their
      mean RTs in trials requiring task-set reconfiguration. This distinct stereotypy
      of cerebral responses reveals different patterns of cognitive control according
      to the DAT1 gene polymorphism.

PMID- 20141528
TI  - Brain transcranial direct current stimulation modulates motor excitability in
      mice.
AB  - Shortly after the application of weak transcranial direct current stimulation
      (tDCS) to the animal and human brain, changes in corticospinal excitability,
      which mainly depend on polarity, duration and current density of the stimulation
      protocol, have been reported. In humans, anodal tDCS has been reported to enhance
      motor-evoked potentials (MEPs) elicited by transcranial brain stimulation while
      cathodal tDCS has been shown to decrease them. Here we investigated the effects
      produced by tDCS on mice motor cortex. MEPs evoked by transcranial electric
      stimulation were recorded from forelimbs of 12 C57BL/6 mice, under sevofluorane
      anaesthesia, before and after (0, 5 and 10 min) anodal and cathodal tDCS (tDCS
      duration 10 min). With respect to sham condition stimulation (anaesthesia), MEP
      size was significantly increased immediately after anodal tDCS, and was reduced
      after cathodal tDCS (approximately 20% vs. sham). Both effects declined towards
      basal levels in the following 10 min. Although the site and mechanisms of action
      of tDCS need to be more clearly identified, the directionality of effects of tDCS
      on mice MEPs is consistent with previous findings in humans. The feasibility of
      tDCS in mice suggests the potential applicability of this technique to assess the
      potential therapeutic options of brain polarization in animal models of
      neurological and neuropsychiatric diseases.

PMID- 20141529
TI  - Impaired dopaminergic neuron development and locomotor function in zebrafish with
      loss of pink1 function.
AB  - Mutations in the human PTEN-induced kinase 1 (PINK1) gene are linked to recessive
      familial Parkinson's disease. Animal models of altered PINK1 function vary
      greatly in their phenotypic characteristics. Drosophila pink1 mutants exhibit
      mild dopaminergic neuron degeneration and locomotion defects. Such defects are
      not observed in mice with targeted null mutations in pink1, although these mice
      exhibit impaired dopamine release and synaptic plasticity. Here, we report that
      in zebrafish, morpholino-mediated knockdown of pink1 function did not cause large
      alterations in the number of dopaminergic neurons in the ventral diencephalon.
      However, the patterning of these neurons and their projections are perturbed.
      This is accompanied by locomotor dysfunction, notably impaired response to
      tactile stimuli and reduced swimming behaviour. All these defects can be rescued
      by expression of an exogenous pink1 that is not a target of the morpholinos used.
      These results indicate that normal PINK1 function during development is necessary
      for the proper positioning of populations of dopaminergic neurons and for the
      establishment of neuronal circuits in which they are implicated.

PMID- 20141530
TI  - Serotonin modulates glutamatergic transmission in the rat olfactory tubercle.
AB  - The olfactory tubercle (OT) is found in the brains of mammals that are highly
      dependent on their sense of smell. Its human analogue is the poorly understood
      anterior perforated substance. Previous work on rat brain slices identified two
      types of field potential responses from the OT. The association fibre (AF)
      pathway was sensitive to muscarinic modulation, whereas the lateral olfactory
      tract (LOT) fibre pathway was not. Here, we establish that serotonin (5
      hydroxytryptamine; 5-HT) also inhibits field potential excitatory postsynaptic
      potentials (EPSPs) in the AF, but not in the LOT fibre, pathway. Parallel
      experiments with adenosine (ADO) excluded ADO mediation of the 5-HT effect.
      Exogenous 5-HT at 30 microm caused a long-lasting approximately 40% reduction in
      the amplitude of AF postsynaptic responses, without affecting the time-course of
      EPSP decline, indicating a fairly restricted disposition of the 5-HT receptors
      responsible. The 5-HT(1)-preferring, 5-HT(5)-preferring and 5-HT(7)-preferring
      agonist 5-carboxamidotryptamine caused similar inhibition at approximately 100
      nm. The 5-HT(1A)-preferring ligand 8-hydroxy-di-n-propylamino-tetralin at 10
      microm, and the 5-HT uptake inhibitor citalopram at 3 microm, caused inhibition
      of AF-stimulated field potential responses in the 5-10% range. Order-of-potency
      information suggested a receptor of the 5-HT(1B) or 5-HT(1D) subtype. The 5
      HT(1D) agonist L-694,247 (1 microm) suppressed the AF response by approximately
      10% when used on its own. After washing out of L-694,427, inhibition by 30 microm
      5-HT was reduced to negligible levels. Allowing for a partial agonist action of L
      694,427 and complex interactions of 5-HT receptors within the OT, these results
      support the presence of active 5-HT(1D)-type receptors in the principal cell
      layer of the OT.

PMID- 20141531
TI  - Targets for the MalI repressor at the divergent Escherichia coli K-12 malX-malI
      promoters.
AB  - Random mutagenesis has been used to identify the target DNA sites for the MalI
      repressor at the divergent Escherichia coli K-12 malX-malI promoters. The malX
      promoter is repressed by MalI binding to a DNA site located from position -24 to
      position -9, upstream of the malX promoter transcript start. The malI promoter is
      repressed by MalI binding from position +3 to position +18, downstream of the
      malI transcript start. MalI binding at the malI promoter target is not required
      for repression of the malX promoter. Similarly, MalI binding at the malX promoter
      target is not required for repression of the malI. Although the malX and malI
      promoters are regulated by a single DNA site for cyclic AMP receptor protein,
      they function independently and each is repressed by MalI binding to a different
      independent operator site.

PMID- 20141532
TI  - Identification and in vitro deoxynucleotidylation of the terminal protein of the
      linear plasmid pAL1 of Arthrobacter nitroguajacolicus Ru61a.
AB  - The plasmid pAL1 of Arthrobacter nitroguajacolicus Ru61a is a linear replicon,
      characterized by inverted terminal repeats and terminal proteins (TPs) covalently
      bound to its 5'-ends. Previous sequence analysis and predictions of possible
      secondary structures formed by telomeric 3'-overhangs indicated significant
      differences of the 'left' and 'right' telomere of pAL1, raising the question of
      whether each terminus is recognized by a specific protein. The genes pAL1.102 and
      pAL1.103, located close to a terminus, code for possible DNA-binding proteins;
      however, only the pORF102 protein encoded by pAL1.102 shows a weak similarity to
      known TPs of Streptomyces linear replicons. pORF102, purified from recombinant A.
      nitroguajacolicus Ru61a as a fusion with maltose-binding protein (MBP), was
      specifically associated with terminal pAL1 DNA, whereas MBP-pORF103 was devoid of
      DNA, suggesting that pORF102 represents the protein attached to both ends of the
      linear plasmid. In electrophoretic mobility shift assays, the MBP-pORF102 protein
      was not capable of specifically recognizing telomeric DNA sequences. Consistent
      with its proposed role as a protein primer in DNA synthesis, pORF102 was
      deoxynucleotidylated in vitro with dCMP, complementary to the 3'-ends (... GCAGG)
      of pAL1.

PMID- 20141533
TI  - Oxalic acid biosynthesis is encoded by an operon in Burkholderia glumae.
AB  - Although the biosynthesis of oxalic acid is known to occur in a number of
      bacteria, the mechanism(s) regulating its production remains largely unknown. To
      date, there is no report on the identification of an oxalic acid biosynthetic
      pathway gene from bacteria. In an attempt to identify such a gene(s), a mutant
      screen was conducted using the simple oxalic acid-producing phytopathogenic
      bacterium, Burkholderia glumae. Four mutants that failed to produce oxalic acid
      were isolated from a transposon-mutagenized B. glumae library and named
      Burkholderia oxalate defective (Bod)1. DNA sequence analysis revealed that each
      mutant contained an insertion event at different sites in the same ORF, which we
      referred to as the oxalate biosynthetic component (obc)A locus. Complementation
      of the Bod1 mutant with the obcA gene, however, resulted only in a partial
      restoration of the oxalic acid-producing phenotype. Further complementation
      studies utilizing a larger DNA fragment encompassing the obcA locus coupled with
      deletion mutagenesis led to the identification of another ORF that we named the
      obcB locus, which was essential for higher levels of oxalic acid production.
      Transcript analysis indicated that both obcA and obcB are coexpressed and encoded
      on a single polycistron message.

PMID- 20141534
TI  - Adenine nucleotide transport via Sal1 carrier compensates for the essential
      function of the mitochondrial ADP/ATP carrier.
AB  - The mitochondrial ADP/ATP carrier (Aac2p) of Saccharomyces cerevisiae links two
      biochemical pathways, glycolysis in the cytosol and oxidative phosphorylation in
      the mitochondria, by exchanging their common substrates and products across the
      inner mitochondrial membrane. Recently, the product of the SAL1 gene, which is
      essential in cells lacking Aac2p, has been implicated in a similar communication.
      However, the mechanism by which Sal1p rescues the growth of Deltaaac2 mutants is
      not clear and it was proposed that both Sal1p and Aac2p share a common vital
      function other than ADP/ATP exchange. Here, the impact of SAL1 deletion on
      mitochondrial reactions involving either synthesis or hydrolysis of ATP was
      investigated. We show that adenine nucleotide transport activity related to Sal1p
      can be demonstrated in isolated mitochondria as well as in intact cells under
      conditions when Aac2-mediated exchange is not functional. Our results indicate
      that the vital role of both Sal1p and Aac2p is to maintain the essential
      intramitochondrial ATP pool owing to their ability to transport adenine
      nucleotides.

PMID- 20141535
TI  - (E)-2-benzylidene-4-phenyl-1,3-diselenole has antioxidant and hepatoprotective
      properties against oxidative damage induced by 2-nitropropane in rats.
AB  - The in vitro effect of (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD) was
      evaluated through iron/EDTA-induced thiobarbituric acid reactive species (TBARS)
      and reactive species (RS) determinations as well as of the scavenging 2,2'
      diphenyl-1-picrylhydrazyl (DPPH) radical quantification. BPD at the
      concentrations of 10 and 50 MUMU decreased RS and TBARS levels, respectively. The
      antioxidant activity was not related to the scavenging DPPH radical mechanism. A
      second objective of this study was to investigate the hepatoprotective action of
      BPD, administered by oral route, against oxidative damage induced by 2
      nitropropane (2-NP) (100 mg/kg of body weight) in liver of rats. At the dose of
      50 mg/kg, BPD protected against the increase in aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities
      induced by 2-NP. BPD (10 and 50 mg/kg) protected against the increase in TBARS
      levels and alkaline phosphatase (ALP) activity. Sections of liver from 2-NP
      exposed rats presented intense infiltration of inflammatory cells and loss of
      cellular architecture. BPD (10 and 50 mg/kg) attenuated 2-NP-induced hepatic
      histological alterations. The inhibition of delta-aminolevulinic dehydratase
      (delta-ALA-D), glutathione peroxidase (GPx), glutathione reductase (GR), and
      glutathione S-transferase (GST) activities and the decreased GSH levels caused by
      2-NP were protected by BPD (50 mg/kg). Catalase activity and ascorbic acid levels
      were not altered by 2-NP. These results demonstrated the antioxidant and
      hepatoprotective effects of BPD in liver of rats.

PMID- 20141536
TI  - Brief screening tool for mild cognitive impairment in older Japanese: validation
      of the Japanese version of the Montreal Cognitive Assessment.
AB  - AIM: The Montreal Cognitive Assessment (MoCA), developed by Dr Nasreddine
      (Nasreddine et al. 2005), is a brief cognitive screening tool for detecting older
      people with mild cognitive impairment (MCI). We examined the reliability and
      validity of the Japanese version of the MoCA (MoCA-J) in older Japanese subjects.
      METHODS: Subjects were recruited from the outpatient memory clinic of Tokyo
      Metropolitan Geriatric Hospital or community-based medical health check-ups in
      2008. The MoCA-J, the Mini-Mental State Examination (MMSE), the revised version
      of Hasegawa's Dementia Scale (HDS-R), Clinical Dementia Rating (CDR) scale, and
      routine neuropsychological batteries were conducted on 96 older subjects. Mild
      Alzheimer's disease (AD) was found in 30 subjects and MCI in 30, with 36 normal
      controls. RESULTS: The Cronbach's alpha of MoCA-J as an index of internal
      consistency was 0.74. The test-retest reliability of MoCA, using intraclass
      correlation coefficient between the scores at baseline survey and follow-up
      survey 8 weeks later was 0.88 (P < 0.001). MoCA-J score was highly correlated
      with MMSE (r = 0.83, P < 0.001), HDS-R (r = 0.79, P < 0.001) and CDR (r = -0.79,
      P < 0.001) scores. The areas under receiver-operator curves (AUC) for predicting
      MCI and AD groups by the MoCA-J were 0.95 (95% confidence interval [CI] = 0.90
      1.00) and 0.99 (95% CI = 0.00-1.00), respectively. The corresponding values for
      MMSE and HDS-R were 0.85 (95% CI = 0.75-0.95) and 0.97 (95% CI = 0.00-1.00), and
      0.86 (95% CI = 0.76-0.95) and 0.97 (95% CI = 0.00-1.00), respectively. Using a
      cut-off point of 25/26, the MoCA-J demonstrated a sensitivity of 93.0% and a
      specificity of 87.0% in screening MCI. CONCLUSION: The MoCA-J could be a useful
      cognitive test for screening MCI, and could be recommended in a primary clinical
      setting and for geriatric health screening in the community.

PMID- 20141537
TI  - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors prevent the
      progression of renal dysfunction in Japanese hypertensive patients.
AB  - AIM: The aim was to determine whether the use of statins prevents the progression
      of chronic kidney disease (CKD) in hypertensive patients. METHODS: We
      retrospectively reviewed data obtained from hypertensive patients, and subjects
      with diabetes mellitus and those undergoing hemodialysis were excluded. At total
      of 227 patients were enrolled (83 men, mean age 73 years) and 90% of the patients
      were of CKD stage 2 or 3. The patients were divided into two groups: those
      treated with statins (n = 93) and those not treated with statins (n = 134). Renal
      function was evaluated by estimated glomerular filtration rate (eGFR). RESULTS:
      The statin group and the non-statin group were similar in age, sex, blood
      pressure, follow-up period and prescriptions of antihypertensive medicines. The
      eGFR in the statin group increased from 62 +/- 14 to 66 +/- 15 (mL/min per 1.73
      m(2)), whereas it decreased in the non-statin group from 69 +/- 16 to 64 +/- 18
      (mL/min per 1.73 m(2)). The annual eGFR improved in the statin group (2.5 +/- 6.6
      mL/min per 1.73 m(2)/year), but decreased in the non-statin group (-3.3 +/- 6.6
      mL/min per 1.73 m(2)/year) (P < 0.001). When the patients were divided into two
      groups by low-density lipoprotein (LDL) cholesterol levels at the second
      evaluation, annual eGFR improved in the group of LDL to below 100 mg/dL (n = 99)
      (0.4 +/- 7.2 mL/min per 1.73 m(2)/year), but decreased in the other group (n =
      128) (-1.9 +/- 7.0 mL/min per 1.73 m(2)/year) (P = 0.018). CONCLUSION: Lipid
      lowering intervention with statins inhibits the progression of CKD in
      hypertensive patients.

PMID- 20141538
TI  - Multilevel analysis of effects of  individual characteristics and  household
      factors on self-rated  health among older adults in  rural Vietnam.
AB  - AIM: This paper aims to describe self-rated health (SRH) status among older
      adults in a rural community of Vietnam, and examine individual and household
      level factors associated with good health rating among the study populations.
      METHODS: The study was carried out in the Bavi district, a rural community
      located 60 km west of Hanoi, the capital, within the Epidemiological Field
      Laboratory of Bavi (FilaBavi) in Vietnam in 2006. All people aged 50 years and
      over who lived within the district were surveyed. Face-to-face household
      interviews were conducted by trained surveyors using standard World Health
      Organization/INDEPTH network questionnaire- summary version. A logistic
      multilevel modeling approach was applied to analyze the association between SRH
      and both individual and household-level factors. RESULTS: The proportion of
      people aged 50 years and older in FilaBavi reported having good/very good health
      and poor/very poor health was 15.1% and 24.8%, respectively. SRH status was
      reported to be better among: (i) men; (ii) younger people; (iii) people with
      higher education; (iv) people who were currently in marital a partnership; (v)
      those from wealthier households; and (vi) those who were living in
      riverside/island or highland areas compared to those of other categories of the
      same variable. CONCLUSION: The findings reveal that there exist problems of
      inequality in health among older adults in the study setting by sex, age,
      education, wealth status and place of residence. We also found a considerable
      contribution of the household-level factors to SRH of the study populations.

PMID- 20141539
TI  - Approaches to reducing the most important patient errors in primary health-care:
      patient and professional perspectives.
AB  - We have previously reported a preliminary taxonomy of patient error. However,
      approaches to managing patients' contribution to error have received little
      attention in the literature. This paper aims to assess how patients and primary
      care professionals perceive the relative importance of different patient errors
      as a threat to patient safety. It also attempts to suggest what these groups
      believe may be done to reduce the errors, and how. It addresses these aims
      through original research that extends the nominal group analysis used to
      generate the error taxonomy. Interviews were conducted with 11 purposively
      selected groups of patients and primary care professionals in Auckland, New
      Zealand, during late 2007. The total number of participants was 83, including 64
      patients. Each group ranked the importance of possible patient errors identified
      through the nominal group exercise. Approaches to managing the most important
      errors were then discussed. There was considerable variation among the groups in
      the importance rankings of the errors. Our general inductive analysis of
      participants' suggestions revealed the content of four inter-related actions to
      manage patient error: Grow relationships; Enable patients and professionals to
      recognise and manage patient error; be Responsive to their shared capacity for
      change; and Motivate them to act together for patient safety. Cultivation of this
      GERM of safe care was suggested to benefit from 'individualised community care'.
      In this approach, primary care professionals individualise, in community spaces,
      population health messages about patient safety events. This approach may help to
      reduce patient error and the tension between personal and population health-care.

PMID- 20141540
TI  - Alternative splicing of Mef2c promoted by Fox-1 during neural differentiation in
      P19 cells.
AB  - Mef2c protein is one of the MADS-box type transcription factors involved in
      muscular differentiation and synaptic formation. Previously, it has been reported
      that the Mef2c gene is responsible for three alternative splicing regulations.
      Here, we investigated the alternative splicing variants of Mef2c during neural
      differentiation of P19 cells and during cardio muscular differentiation of P19
      clone 6 (P19CL6). We detected that two Mef2c mRNA isoforms, using exon alpha1
      with and without the gamma region at exon 10, are mainly produced in immature P19
      cells. Remarkably, Mef2c isoforms containing exon beta specifically appeared in
      the neural cell stage. Because most transcripts contain exon beta in the neural
      cell stage and in the brain, this suggests that the alternative splicing of exon
      beta is highly regulated. Among known regulators, Fox-1 was specifically
      expressed in the neural cell stage in correlation with Mef2c exon beta. Fox-1
      promoted exon beta inclusion in transfection experiments using Mef2cbeta
      minigene. Moreover, we found that the promotion required RNA-binding activity of
      Fox-1 and GCAUG sequence located in adjacent intron of exon beta. Taken together,
      our results suggest that Fox-1, expressed specifically in the neural cell stage,
      promoted Mef2c exon beta inclusion via the GCAUG. 

PMID- 20141541
TI  - Changes in chromatin structure and methylation of the human interleukin-1beta
      gene during monopoiesis.
AB  - SUMMARY: Interleukin-1beta (IL-1beta) induces the expression of a variety of
      proteins responsible for acute inflammation and chronic inflammatory diseases.
      However, the molecular regulation of IL-1beta expression in myeloid
      differentiation has not been elucidated. In this study the chromatin structure of
      the IL-1beta promoter and the impact of methylation on IL-1beta expression in
      monocytic development were examined. The results revealed that the IL-1beta
      promoter was inaccessible in undifferentiated promyeloid HL-60 cells but highly
      accessible in differentiated monocytic cells which additionally acquired the
      ability to produce IL-1beta. Accessibilities of differentiated cells were
      comparable to those of primary monocytes. Lipopolysaccharide (LPS) stimulation
      did not affect promoter accessibility in promyeloid and monocytic HL-60 cells,
      demonstrating that the chromatin remodelling of the IL-1beta promoter depends on
      differentiation and not on the transcriptional status of the cell. Demethylation
      via 5-aza-2'-deoxycytodine led to the induction of IL-1beta expression in
      undifferentiated and differentiated cells, which could be increased after LPS
      stimulation. Our data indicate that the IL-1beta promoter is reorganized into an
      open poised conformation during monopoiesis being a privilege of mature monocytes
      but not of the entire myeloid lineage. As a second mechanism, IL-1beta expression
      is regulated by methylation acting independently of the developmental stage of
      myeloid cells.

PMID- 20141544
TI  - FcepsilonRIalpha gene (FCER1A) promoter polymorphisms and total serum IgE levels
      in Japanese atopic dermatitis patients.
AB  - Two promoter polymorphisms of the high-affinity IgE receptor alpha-subunit
      (FcepsilonRIalpha) gene (FCER1A), -66T>C (rs2251746) and -315C>T (rs2427827),
      were analysed in Japanese atopic dermatitis subjects. Patients with the -315CT/TT
      genotype tended to have higher total serum IgE levels, while the proportion of 
      315CT/TT genotype or the -315T allele was significantly higher in those with
      highly elevated total serum IgE concentrations.

PMID- 20141543
TI  - Enhancement of effector CD8+ T-cell function by tumour-associated B7-H3 and
      modulation of its counter-receptor triggering receptor expressed on myeloid cell
      like transcript 2 at tumour sites.
AB  - SUMMARY: B7-H3 is a B7-family co-stimulatory molecule and is broadly expressed on
      various tissues and immune cells. Transduction of B7-H3 into some tumours
      enhances anti-tumour responses. We have recently found that a triggering receptor
      expressed on myeloid cell-like transcript 2 (TLT-2) is a receptor for B7-H3.
      Here, we examined the roles of tumour-associated B7-H3 and the involvement of TLT
      2 in anti-tumour immunity. Ovalbumin (OVA)(257-264)-specific OT-I CD8(+) T cells
      exhibited higher cytotoxicity against B7-H3-transduced OVA-expressing tumour
      cells (B7-H3/E.G7) in vitro and selectively eliminated B7-H3/E.G7 cells in vivo.
      The presence of B7-H3 on target cells efficiently augmented CD8(+) T-cell
      mediated cytotoxicity against alloantigen or OVA, whereas the presence of B7-H3
      in the priming phase did not affect the induced cytotoxicity. B7-H3 transduction
      into five tumour cell lines efficiently reduced their tumorigenicity and
      regressed growth. Treatment with either anti-B7-H3 or anti-TLT-2 monoclonal
      antibody accelerated growth of a tumour that expressed endogenous B7-H3,
      suggesting a co-stimulatory role of the B7-H3-TLT-2 pathway. The TLT-2 was
      preferentially expressed on CD8(+) T cells in regional lymph nodes, but was down
      regulated in tumour-infiltrating CD8(+) T cells. Transduction of TLT-2 into OT-I
      CD8(+) T cells enhanced antigen-specific cytotoxicity against both parental and
      B7-H3-transduced tumour cells. Our results suggest that tumour-associated B7-H3
      directly augments CD8(+) T-cell effector function, possibly by ligation of TLT-2
      on tumour-infiltrating CD8(+) T cells at the local tumour site.

PMID- 20141542
TI  - Lipopolysaccharide induces calcitonin gene-related peptide in the RAW264.7
      macrophage cell line.
AB  - SUMMARY: Calcitonin gene-related peptide (CGRP) is widely distributed and plays
      important roles in a wide array of biological functions. It is enriched in
      primary sensory neurons and hence involved in nociception and neurogenic
      inflammation. Recent studies have shown that CGRP can be produced by immune cells
      such as monocytes/macrophages following inflammatory stimulation, suggesting a
      role in innate immunity. However, it is unclear how CGRP is up-regulated in
      macrophages and if it plays a role in macrophage functions such as the production
      of cytokines and chemokines. Using enzyme-linked immunosorbent assay (ELISA) and
      multiplex ELISA, lipopolysaccharide (LPS) was found to induce CGRP in the RAW
      264.7 macrophage cell line. LPS-induced inflammatory mediators such as nerve
      growth factor (NGF), interleukin-1beta (IL-1beta), IL-6, prostaglandin E(2)
      (PGE(2)) and nuclear factor-kappaB (NF-kappaB) signalling are involved in
      inducing CGRP, whereas the NGF receptor trkA and CGRP receptor signalling
      pathways are unexpectedly involved in suppressing LPS-induced CGRP, which leads
      to the fine-tune regulation of CGRP release. Exogenous CGRP and CGRP receptor
      antagonists, in a concentration-dependent manner, stimulated, inhibited or had no
      effect on basal or LPS-induced release of monocyte chemoattractant protein-1, IL
      1beta, IL-6, tumour necrosis factor-alpha and IL-10 in RAW macrophages. The
      ligand-concentration-dependent regulation of the production of inflammatory
      mediators by CGRP receptor signalling is a novel mechanism underlying the
      stimulating and suppressing role of CGRP in immune and inflammatory responses.
      Together, our data suggest that monocytes/macrophages are an important source of
      CGRP. Inflammation-induced CGRP has a positive or negative reciprocal effect on
      the production of other pro- and anti-inflammatory mediators. Thereby CGRP plays
      both facilitating and suppressing roles in immune and inflammatory responses.

PMID- 20141545
TI  - Dimorphism of TAP-1 gene in Caucasian with juvenile myoclonic epilepsy and in
      Tunisian with idiopathic generalized epilepsies.
AB  - Juvenile myoclonic epilepsy (JME) is the most common form of idiopathic
      generalized epilepsies (IGE) that account for about 5-10% of all types of
      epilepsies. The first putative locus termed EJM1 is on the human leucocyte
      antigen (HLA-II) region of chromosome 6p21.3. Interestingly, the EJM1 region
      includes the Transporter associated with antigen processing 1 (TAP-1) gene
      encoding the TAP-1, and previous studies have reported associations between HLA
      II polymorphisms and different types of epilepsy. In this study, we report an
      association between two TAP-1 functional polymorphisms the I333V and the D637G
      and most common IGE in Tunisian population, but we fail to find significant
      results in Caucasian with JME.

PMID- 20141546
TI  - AKT1 polymorphisms are associated with tuberculosis in the Chinese population.
AB  - AKT1, a serine/threonine kinase, plays a critical role in the controlling of
      intracellular growth of Mycobacterium tuberculosis. In this study, we
      investigated whether polymorphisms in AKT1 affect susceptibility to tuberculosis
      (TB). Two single nucleotide polymorphisms of AKT1, IVS3+18C>T and +726G>A were
      genotyped in Chinese patients with pulmonary TB by polymerase chain reaction
      restriction fragment length polymorphism. Patients with pulmonary TB had
      significantly lower IVS3+18 C/C genotype and higher C/T genotype compared with
      age-, gender- and ethnically matched controls (P < 0.05). The T-A haplotype
      frequency was significantly higher in patients than in controls (P < 0.05). In
      conclusion, our result indicates that AKT1 polymorphisms are associated with
      susceptibility to pulmonary TB.

PMID- 20141547
TI  - Ecology of coliphages in southern California coastal waters.
AB  - AIMS: This study aims to investigate the ecology of coliphages, an important
      microbial pollution indicator. Specifically, our experiments address (i) the
      ability of environmental Escherichia coli (E. coli) to serve as hosts for
      coliphage replication, and (ii) the temporal and spatial distribution of
      coliphages in coastal waters. METHODS AND RESULTS: Water samples from three
      locations in California's Newport Bay watershed were tested for the presence of
      coliphages every 2 weeks for an entire year. A total of nine E. coli strains
      isolated from various sources served as hosts for coliphage detection. Coliphage
      occurrence was significantly different between freshwater, estuarine and coastal
      locations and correlated with water temperature, salinity and rainfall in the
      watershed. The coliphages isolated on the environmental hosts had a broad host
      range relative to the coliphages isolated on an E. coli strain from sewage and a
      US EPA recommended strain for coliphage detection. CONCLUSIONS: Coliphage
      occurrence was related to the temperature, rainfall and salinity within the bay.
      The adaptation to a broad host-range may enable the proliferation of coliphages
      in the aquatic environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding
      the seasonal variation of phages is useful for establishing a background level of
      coliphage presence in coastal waters. The broad host-range of coliphages isolated
      on the environmental E. coli host calls for investigation of coliphage
      replication in the aquatic environment.

PMID- 20141548
TI  - Assessment of SCAR markers to design real-time PCR primers for rhizosphere
      quantification of Azospirillum brasilense phytostimulatory inoculants of maize.
AB  - AIMS: To assess the applicability of sequence characterized amplified region
      (SCAR) markers obtained from BOX, ERIC and RAPD fragments to design primers for
      real-time PCR quantification of the phytostimulatory maize inoculants
      Azospirillum brasilense UAP-154 and CFN-535 in the rhizosphere. METHODS AND
      RESULTS: Primers were designed based on strain-specific SCAR markers and were
      screened for successful amplification of target strain and absence of cross
      reaction with other Azospirillum strains. The specificity of primers thus
      selected was verified under real-time PCR conditions using genomic DNA from
      strain collection and DNA from rhizosphere samples. The detection limit was 60 fg
      DNA with pure cultures and 4 x 10(3) (for UAP-154) and 4 x 10(4) CFU g(-1) (for
      CFN-535) in the maize rhizosphere. Inoculant quantification was effective from
      10(4) to 10(8) CFU g(-1) soil. CONCLUSION: BOX-based SCAR markers were useful to
      find primers for strain-specific real-time PCR quantification of each A.
      brasilense inoculant in the maize rhizosphere. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Effective root colonization is a prerequisite for successful Azospirillum
      phytostimulation, but cultivation-independent monitoring methods were lacking.
      The real-time PCR methods developed here will help understand the effect of
      environmental conditions on root colonization and phytostimulation by A.
      brasilense UAP-154 and CFN-535.

PMID- 20141550
TI  - Radiation port xanthogranuloma: solitary xanthogranuloma occurring within the
      irradiated skin of a breast cancer patient-report and review of cutaneous
      neoplasms developing at the site of radiotherapy.
AB  - Xanthogranulomas are benign lesions composed of macrophages in which some of the
      cells have vacuolated cytoplasm. They commonly occur in children, referred to as
      juvenile xanthogranulomata, and are histopathologically characterized by the
      presence of Touton giant cells. Xanthogranuloma can also occur in adults. A woman
      who developed a solitary xanthogranuloma within the field of radiotherapy
      following treatment of her breast cancer is reported. In addition to
      xanthogranuloma, other benign lesions of keratinocytes, mast cells, endothelial
      cells and lymphatic cells have been observed at the site of radiation treatment.
      Also, several malignancies, including hematopoietic cancers, sarcomas, metastatic
      cancers and common skin cancers, have been observed within radiation ports. A
      causal relationship in the development of our patient's xanthogranuloma is
      suggested by the temporal association between the treatment with radiotherapy and
      the subsequent appearance of a xanthogranuloma directly within the radiation
      field.

PMID- 20141549
TI  - Mankind's first natural stem cell transplant.
AB  - The timing of the umbilical cord clamping at birth is still controversial. In the
      modern era of medicine, the cord has been clamped early to facilitate
      resuscitation and stabilization of infants. However, recently delayed cord
      clamping has been supported by physicians because it allows for the physiological
      transfer of blood from the placenta to the infant. Many clinical studies have
      revealed that the delayed cord clamping elevates blood volume and haemoglobin and
      prevents anaemia in infants. Moreover, since it was known that umbilical cord
      blood contains various valuable stem cells such as haematopoietic stem cells,
      endothelial cell precursors, mesenchymal progenitors and multipotent/pluripotent
      lineage stem cells, the merit of delayed cord clamping has been magnified. In
      this review, we discuss the advantages and disadvantages of delayed cord clamping
      at birth. We highlight the importance of delayed cord clamping in realizing
      mankind's first stem cell transfer and propose that it should be encouraged in
      normal births.

PMID- 20141551
TI  - Diagnosis of cutaneous tumors with in vivo confocal laser scanning microscopy.
AB  - In recent years, in vivo confocal laser scanning microscopy (CLSM) has become an
      established method for the non-invasive examination of the skin. In vivo CLSM
      allows for real-time imaging of micro-anatomic cutaneous structures. It has been
      used to diagnose ambiguous skin tumors and to measure subclinical tumor spread
      prior to surgery. By additionally providing high power morphologic information,
      in vivo CLSM helps to reduce unnecessary biopsies. A multitude of diagnostic
      features for skin tumors has been published. Here we review published diagnostic
      in vivo CLSM features, and compare them to our own experience in 100 tumors. In
      combination with clinical examination and dermatoscopy, in vivo CLSM is a
      valuable additional tool for non-invasive skin tumor diagnosis.

PMID- 20141552
TI  - Bleedings into the anterior aspect of the intervertebral disks in the lumbar
      region of the spine as a diagnostic sign of hanging.
AB  - Simon's hemorrhages are ventral intervertebral hemorrhages located beneath the
      anterior longitudinal ligament that have been described in cases of hanging and
      tend to appear in the lumbar region of the spine. There are also reports of
      Simon's hemorrhages in cases of blunt trauma, asphyxia, drowning, and
      putrefaction. In a prospective analysis of 2226 autopsies, we found Simon's
      hemorrhages in 65 out of 178 cases of hanging and also in 17 cases in a group of
      350 controls with various causes of death. The relative frequency of occurrence
      of Simon's bleedings in cases of hanging was 37%. Simon's hemorrhages can be
      considered an objective vital finding, which is not absolutely specific for
      hanging. The absence of hemorrhages in intervertebral disks does not exclude
      death by hanging. This study suggests that Simon's bleedings in cases of hanging
      are more frequent in rather young individuals, in cases with free body
      suspension, and in individuals with minimal degenerative changes in the
      lumbosacral part of the spinal column.

PMID- 20141553
TI  - An explosion of a CNG fuel vessel in an urban bus.
AB  - An investigation is presented of the explosion of a CNG (compressed natural gas)
      fuel vessel, called a liner, in an urban bus. The explosion happened at a gas
      station 10 min after filling was completed. There were no traces of soot and
      flames at the failed liner, which would be indicative of explosion by ignition of
      the gas. The filling process of the station was automatically monitored and
      recorded in a computer. There was no unusual record of the filling system that
      indicated excess pressure at the time of the accident. There were cracks on the
      liner that were initiated at the outer surface of the cylindrical shell located
      at a point 4 cm above the lower dome where cracks did not originate easily as a
      result of overload. Chemical analysis was performed on a specimen that was cut
      from the liner, and there was no peculiarity in the mix. Mechanical analysis was
      performed on the specimens and showed that the hardness was not in the specified
      range because of inadequate heat treatment of the metal. The hardness of the
      liner was strictly controlled in the manufacturing process. All the liners that
      were manufactured at the same period with the failed liner were recalled for
      examination.

PMID- 20141554
TI  - Discrimination of falls and blows in blunt head trauma: a multi-criteria
      approach.
AB  - In the discrimination of falls versus blows, the hat brim line (HBL) rule is
      mentioned in several textbooks as the most useful single criterion. Recent
      studies, however, have found that the HBL rule is only moderately valid and that
      its use on its own is not recommended. The purpose of this 6-year retrospective
      study was to find additional individually useful criteria in the distinction of
      falls from blows. Overall, the following criteria were found to point toward
      blows: more than three lacerations, laceration length of 7 cm or more, comminuted
      or depressed calvarial fractures, lacerations or fractures located above the HBL,
      left-side lateralization of lacerations or fractures, more than four facial
      contusions or lacerations, presence of ear lacerations, presence of facial
      fractures, and presence of postcranial osseous and/or visceral trauma. Based on
      the most discriminating criteria, a decision tree was constructed to be
      potentially applicable to future cases.

PMID- 20141555
TI  - Comparison of frequentist methods for estimating the total weight of consignments
      of drugs.
AB  - A topic in forensic statistics is the estimation of the total weight of
      consignments of drugs based on subsamples of which a certain fraction may not
      contain drugs at all. The frequentist approach to this concentrates on obtaining
      confidence intervals for the total weight, based on estimation of the fraction of
      drugs and the mean and variance of the weights of drug units. The current study
      shows that the resulting confidence intervals are basically unreliable, since
      they are based on an underestimation of the variation of the underlying
      statistical process. Two alternatives are given that yield asymptotically correct
      results. These are not reliable for small subsamples either, though, because of
      the inherent multimodal behaviour of the sample mean. In cases where a relatively
      large fraction of the consignment contains no drugs, the confidence intervals
      reported in the literature should not be used in practice.

PMID- 20141556
TI  - An animal model to investigate effectiveness and safety of conducted energy
      weapons (including TASER devices).
AB  - Conducted energy weapons (CEWs) are used by law-enforcement personnel to
      incapacitate individuals quickly and effectively, without causing lethality. CEWs
      have been deployed for relatively long or repeated exposures during law
      enforcement operations. The purpose of this technical note is to describe, in
      detail, some aspects of an anesthetized swine model used in our laboratory and to
      answer specific questions related to the model. In particular,
      tiletamine/zolazepam-induced, propofol-maintained anesthesia appears to be a
      useful technique for studying effects of CEW applications on muscle contraction
      and blood factors such as muscle enzymes. Because effects of CEWs on breathing
      have not been fully elucidated, a spontaneously breathing model is preferable to
      one in which mechanical ventilation is supplied. Placement of the swine in a
      supine position may facilitate measurement of muscle contractions, without
      compromising other physiological parameters.

PMID- 20141557
TI  - Age estimation using thoracic and first two lumbar vertebral ring epiphyseal
      union.
AB  - Union of the vertebral centra or "ring" epiphyses occurs during adolescence and
      early adulthood, providing valuable age at death information. We present a system
      for estimating age based on the timing and pattern of vertebral ring union. Data
      from 57 known individuals aged 14-27 years were used to establish age ranges for
      various patterns of union in females and males. Female age ranges were more well
      defined with less overlap in patterns of union than male age ranges. The age
      ranges are accompanied by descriptions of the stages of union observed that aid
      in applying this method. A test of interobserver error in scoring stages of union
      demonstrated strong consistency among three observers (r = 0.91-0.97). Estimating
      age by observing all stages documented resulted in 78%, 88%, and 100% accuracies
      using vertebral data alone. We encourage the continued use of this method, in
      conjunction with other age indicators.

PMID- 20141558
TI  - Forensic discrimination of dyed hair color: I. UV-visible microspectrophotometry.
AB  - Current protocols for examining hair do not attempt to differentiate hair color
      using instrumental analysis. In this study, hair samples treated with 55
      different red hair dyes were analyzed using UV-visible microspectrophotometry
      between 200 and 700 nm. Using air as a background reference gave the best
      results, although mounting media such as glycerin could also be used. The
      contribution of the hair substrate is predominantly observed in the range of 300
      400 nm while the dye peak is evident in the range of 425-550 nm. It was found
      that the presence of hair dye reduces the overall intrasample variability of the
      hair color. In addition, visual inspection and spectral interpretation showed
      that dyed hair exhibits distinct and discernable shades. The color of all samples
      was stable during storage and while all hair dyes fade with washing, significant
      fading of the color was only evident after daily washing for 3 weeks.

PMID- 20141559
TI  - Quantitative analysis of gamma-hydroxybutyrate at endogenous concentrations in
      hair using liquid chromatography tandem mass spectrometry.
AB  - A method capable of quantifying endogenous concentrations of gamma
      hydroxybutyrate (GHB) in human head hair was developed and validated using liquid
      chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Hair was digested
      under alkaline conditions, and GHB was isolated using liquid-liquid extraction.
      LC/MS/MS was performed using atmospheric pressure chemical ionization in the
      negative mode, multiple reaction monitoring, and deuterated internal standard
      (GHB-D(6)). Linearity was observed between 0.1 and 100 ng/mg GHB (R(2) = 1.000).
      The limits of detection and quantitation in human hair were 0.2 and 0.4 ng/mg,
      respectively. Accuracy at 2 ng/mg and 10 ng/mg was determined to be 97% and 94%,
      and intra-assay CVs at these concentrations were 5.2% and 7.4% (n = 4). Beta
      hydroxybutyrate (BHB), alpha-hydroxybutyrate, gamma-butyrolactone, and 1,4
      butanediol did not produce an interference, and there was negligible ion
      suppression or enhancement from the matrix.

PMID- 20141560
TI  - Critical study of observation of the sternal end of the right 4th rib.
AB  - Studies of the method of estimating age at death by the 4th rib exclusively
      concerned the phase method without fundamentally challenging the method as such.
      The present study analyzed observation of the variables on which the Iscan method
      is based. Ten observers made two assessments of the stage of pit depth, pit
      shape, rim and wall configurations of 59 right 4th ribs harvested from males
      (mean age: 49 years; range: 47-94 years). Observation showed poor reproducibility
      and repeatability for all three variables (Wilcoxon test, kappa-coefficient).
      Analysis of problem ribs revealed difficulty in measuring and imprecision in
      describing pit depth and failure to take account of continual aging for the other
      two variables. Despite these results, Iscan's variables provide objective
      information on age at death. It is recommended that the method be improved by
      better description of the variables and use of multivariate statistical analysis.

PMID- 20141561
TI  - The influence of penetrative trauma on the rate of decomposition.
AB  - An understanding of the factors affecting decomposition is important for the
      accurate estimation of postmortem interval. An experimental study on the
      influence of penetrating trauma on decomposition rate was carried out using the
      domestic pig, Sus scrofa. The results of this study were: (i) Diptera were
      preferentially attracted to and oviposited at natural orifices. Trauma sites were
      not preferentially selected for oviposition; (ii) no differences between trauma
      and non-trauma groups were found in time to skeletonization, weight loss (p =
      0.906), total body score (p = 0.824), body temperature (p = 0.967), or changes in
      soil pH (p = 0.684); and (iii) the effect of investigator disturbance was
      significant when decomposition was measured as weight loss (p = 0.000). This
      study suggests that penetrating trauma of the type used in this study cannot be
      considered a major factor in the rate of decomposition and time to
      skeletonization of a gunshot trauma victim.

PMID- 20141562
TI  - A statistical validation of the individuality and repeatability of striated tool
      marks: screwdrivers and tongue and groove pliers.
AB  - Tool mark identification relies on the premise that microscopic imperfections on
      a tool's working surface are sufficiently unique and faithfully transferred to
      enable a one-to-one association between a tool and the tool marks it creates.
      This paper presents a study undertaken to assess the validity of this premise. As
      part of this study sets of striated tool marks were created under different
      conditions and on different media. The topography of these tool marks was
      acquired and the degree of similarity between them was quantified using well
      defined metrics. An analysis of the resulting matching and nonmatching similarity
      distributions shows nearly error-free identification under most conditions. These
      results provide substantial support for the validity of the premise of tool mark
      identification. Because the approach taken in this study relies on a quantifiable
      similarity metric, the results have greater repeatability and objectivity than
      those obtained using less precise measures of similarity.

PMID- 20141563
TI  - Weak associations between human leucocyte antigen genotype and acute myocardial
      infarction.
AB  - OBJECTIVES: Human leucocyte antigens (HLAs) are polymorphic molecules involved in
      antigen presentation. Associations between HLA type and autoimmune diseases, such
      as type 1 diabetes and rheumatoid arthritis, are well established but the
      potential association of genetic variation affecting antigen presentation with
      cardiovascular disease has not been systematically investigated in large cohorts.
      The importance of such studies is stressed by recent experimental findings of an
      involvement of autoimmunity in the atherosclerotic disease process. RESULTS: An
      SSP-PCR method was used for HLA genotyping to determine associations of HLA-DRB1,
      -DQA1 and -DQB1 with cardiovascular disease in a population-based cohort of 1188
      acute myocardial infarction (AMI) patients and 1191 matched healthy controls. The
      HLA-DRB1*0101 allele, as well as the HLA-DRB1*0101-DQA1*01-DQB1*05 haplotype, was
      found to be associated with increased risk for AMI (OR 1.24; 95% CI 1.00-1.54 for
      both). In contrast, the DRB1*07 and DQA*02 alleles (OR 0.78; 95% CI 0.65-0.95 for
      both), as well as the DRB1*07-DQA*02-DQB*02 haplotype, conferred protection (OR
      0.79; 95% CI 0.63-0.98). An HLA risk score taking each individual's both
      haplotypes into account was higher amongst cases (2.43 +/- 0.92 vs. 2.29 +/-
      0.95, P = 0.001). The association between HLA risk score and AMI was independent
      of other cardiovascular risk factors assessed. CONCLUSIONS: This study
      demonstrates that the associations between HLA-DRB1 and DQA1 loci and
      cardiovascular disease exists but that they are considerably weaker than those
      previously reported for other diseases with an established autoimmune aetiology
      such as type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.

PMID- 20141564
TI  - Gender difference of association between LDL cholesterol concentrations and
      mortality from coronary heart disease amongst Japanese: the Ibaraki Prefectural
      Health Study.
AB  - OBJECTIVE: The aim of this study was to examine whether LDL cholesterol raises
      the risk of coronary heart disease in a dose-response fashion in a population
      with low LDL-cholesterol levels. DESIGN: Population-based prospective cohort
      study in Japan. SUBJECTS AND MAIN OUTCOME MEASURES: A total of 30,802 men and
      60,417 women, aged 40 to 79 years with no history of stroke or coronary heart
      disease, completed a baseline risk factor survey in 1993. Systematic mortality
      surveillance was performed through 2003 and 539 coronary heart disease deaths
      were identified. RESULTS: The mean values for LDL-cholesterol were 110.5 mg dL(
      1) (2.86 mmol L(-1)) for men and 123.9 mg dL(-1) (3.20 mmol L(-1)) for women. Men
      with LDL-cholesterol > or =140 mg dL(-1) (> or =3.62 mmol L(-1)) had two-fold
      higher age-adjusted risk of mortality from coronary heart disease than did those
      with LDL-cholesterol <80 mg dL(-1) (<2.06 mmol L(-1)), whereas no such
      association for women was found. The multivariable hazard ratio for the highest
      versus lowest categories of LDL-cholesterol was 2.06 (95 percent confidence
      interval: 1.34 to 3.17) for men and 1.16 (0.64 to 2.12) for women. CONCLUSION:
      Higher concentrations of LDL-cholesterol were associated with an increased risk
      of mortality from coronary heart disease for men, but not for women, in a low
      cholesterol population.

PMID- 20141565
TI  - No improvement in cardiovascular risk factors in overweight and obese subjects
      after supplementation with vitamin D3 for 1 year.
AB  - BACKGROUND AND AIM: Cross-sectional studies indicate vitamin D to be of
      importance for glucose tolerance, blood pressure and serum lipids, but whether
      supplementation with vitamin D would improve cardio-vascular risk factors is not
      known. DESIGN AND SETTING: The study was a 1 year, double blind placebo
      controlled intervention trial performed at the University Hospital of North
      Norway from November 2005 to October 2007. Subjects. A total of 438 overweight or
      obese subjects, 21-70 years old, were included and 330 completed the study.
      INTERVENTIONS: The subjects were randomized to vitamin D (cholecalciferol,
      vitamin D(3)) 40 000 IU per week (DD group), vitamin D 20 000 IU per week (DP
      group), or placebo (PP group). All subjects were given 500 mg calcium daily. MAIN
      OUTCOME MEASURES: Fasting serum lipids and blood pressure were measured and an
      oral glucose tolerance test performed at start and end of the study. RESULTS: At
      baseline the mean serum 25(OH)D levels were 58 nmol L(-1) (all subjects) and
      increased to 140 and 101 nmol L(-1) in the DD and DP groups, respectively. No
      significant differences were found between the three groups regarding change in
      measures of glucose metabolism or serum lipids. In the DP group, there was a
      slight but significant increase in systolic blood pressure compared with the
      placebo group. CONCLUSIONS: Our results do not support a positive effect of
      vitamin D on glucose tolerance, blood pressure or serum lipids. Further studies
      in subjects with low serum 25(OH)D levels combined with impaired glucose
      tolerance, hypertension or dyslipidaemia are needed.

PMID- 20141566
TI  - Cardiovascular outcomes and their relationships to lipoprotein components in
      patients with and without chronic kidney disease: results from the IDEAL trial.
AB  - OBJECTIVES: In Incremental Decrease in Endpoints through Aggressive Lipid
      lowering (IDEAL), we compared cardiovascular outcomes in patients with and
      without chronic kidney disease (CKD) (estimated glomerular filtration rate <60 mL
      min(-1) 1.73 m(-2)) and analysed relationships between lipoprotein components
      (LC) and major coronary events (MCE) and other cardiovascular (CV) events.
      DESIGN: Exploratory analysis of CV endpoints in a randomized trial comparing high
      dose of atorvastatin to usual dose of simvastatin on MCE. SETTINGS: Patients with
      CKD were compared with the non-CKD patients. Cox regression models were used to
      study the relationships between on-treatment levels of LC and incident MCE.
      FINDINGS: Chronic kidney disease was strongly associated with cardiovascular end
      points including total mortality. In patients with CKD, a significant benefit of
      high dose atorvastatin treatment was found for any CV events, stroke and
      peripheral artery disease, but not for MCE. However, all cardiovascular end
      points except stroke and CV mortality were reduced in the non-CKD group.
      Differential changes in LC or relationships to LC could not explain the different
      treatment outcomes in MCE in the two groups. INTERPRETATION: Chronic kidney
      disease was a powerful risk factor for all cardiovascular end-points. The reason
      why the significant reductions achieved by high-dose statin treatment in most CV
      end-points in the non-CKD group were only in part matched by similar reductions
      in the CKD patients is not apparent. This difference did not result from
      differential changes in or relations to LC, but limited power may have increased
      the possibility of chance findings.

PMID- 20141567
TI  - Long-term effects of weight loss with a very low carbohydrate and low fat diet on
      vascular function in overweight and obese patients.
AB  - OBJECTIVE: To compare the effects of an energy reduced very low carbohydrate,
      high saturated fat diet (LC) and an isocaloric high carbohydrate, low fat diet
      (LF) on endothelial function after 12 months. DESIGN AND SUBJECTS: Forty-nine
      overweight or obese patients (age 50.0 +/- 1.1 years, BMI 33.7 +/- 0.6 kg m(-2))
      were randomized to either an energy restricted ( approximately 6-7 MJ), planned
      isocaloric LC or LF for 52 weeks. Body weight, endothelium-derived factors, flow
      mediated dilatation (FMD), adiponectin, augmentation index (AIx) and pulse wave
      velocity (PWV) were assessed. All data are mean +/- SEM. RESULTS: Weight loss was
      similar in both groups (LC -14.9 +/- 2.1 kg, LF -11.5 +/- 1.5 kg; P = 0.20).
      There was a significant time x diet effect for FMD (P = 0.045); FMD decreased in
      LC (5.7 +/- 0.7% to 3.7 +/- 0.5%) but remained unchanged in LF (5.9 +/- 0.5% to
      5.5 +/- 0.7%). PWV improved in both groups (LC -1.4 +/- 0.6 m s(-1), LF -1.5 +/-
      0.6 m s(-1); P = 0.001 for time) with no diet effect (P = 0.80). AIx and VCAM-1
      did not change in either group. Adiponectin, eSelectin, tPA and PAI-1 improved
      similarly in both groups (P < 0.01 for time). CONCLUSION: Both LC and LF
      hypoenergetic diets achieved similar reductions in body weight and were
      associated with improvements in PWV and a number of endothelium-derived factors.
      However, the LC diet impaired FMD suggesting chronic consumption of a LC diet may
      have detrimental effects on endothelial function.

PMID- 20141568
TI  - Metabolic alterations induced by ischemia in primary cultures of astrocytes:
      merging 13C NMR spectroscopy and metabolic flux analysis.
AB  - Disruption of brain energy metabolism is the hallmark of cerebral ischemia, a
      major cause of death worldwide. Astrocytes play a key role in the regulation of
      brain metabolism and their vulnerability to ischemia has been described. Aiming
      to quantify the effects of an ischemic insult in astrocytic metabolism, primary
      cultures of astrocytes were subjected to 5 h of oxygen and glucose deprivation in
      a bioreactor. Flux distributions, before and after ischemia, were estimated by
      metabolic flux analysis using isotopic information and the consumption/secretion
      rates of relevant extracellular metabolites as constraints. During ischemia and
      early recovery, 30% of cell death was observed; several metabolic alterations
      were also identified reflecting a metabolic response by the surviving cells. In
      the early recovery ( approximately 10 h), astrocytes up-regulated glucose
      utilization by 30% and increased the pentose phosphate pathway and tricarboxylic
      acid cycle fluxes by three and twofold, respectively. Additionally, a two to
      fivefold enhancement in branched-chain amino acids catabolism suggested the
      importance of anaplerotic molecules to the fast recovery of the energetic state,
      which was corroborated by measured cellular ATP levels. Glycolytic metabolism was
      predominant in the late recovery. In summary, this work demonstrates that changes
      in fluxes of key metabolic pathways are implicated in the recovery from ischemia
      in astrocytes.

PMID- 20141569
TI  - Copper binding regulates intracellular alpha-synuclein localisation, aggregation
      and toxicity.
AB  - Alpha-synuclein is a natively unfolded protein that aggregates and forms
      inclusions that are associated with a range of diseases that include Parkinson's
      Disease and Dementia with Lewy Bodies. The mechanism behind the formation of
      these inclusions and their possible role in disease remains unclear. Alpha
      synuclein has also been shown to bind metals including copper and iron. We used a
      cell culture model of alpha-synuclein aggregation to examine the relationship
      between metals and formation of aggregates of the protein. While the levels of
      iron appear to have no role in aggregate formation or localisation of the protein
      in cells, copper appears to be important for both aggregation and cellular
      localisation of alpha-synuclein. Reduction in cellular copper resulted in a great
      decrease in aggregate formation both in terms of large aggregates visible in
      cells and oligomers observed in western blot analysis of cell extracts. Reduction
      in copper also resulted in a change in localisation of the protein which became
      more intensely localised to the plasma membrane in medium with low copper. These
      changes were reversed when copper was restored to the cells. Mutants of the
      copper binding domains altered the response to copper. Deletion of either the N-
      or C-termini resulted in a loss of aggregation while deletion of the C-termini
      also resulted in a loss of membrane association. Increased expression of alpha
      synuclein also increased cell sensitivity to the toxicity of copper. These
      results suggest that the potential pathological role of alpha-synuclein
      aggregates is dependent upon the copper binding capacity of the protein.

PMID- 20141570
TI  - Functional and physical interactions between formyl-peptide-receptors and
      scavenger receptor MARCO and their involvement in amyloid beta 1-42-induced
      signal transduction in glial cells.
AB  - Recent studies suggest that the chemotactic G protein-coupled receptor formyl
      peptide-receptor-like-1 (FPRL1) or the scavenger receptor MARCO (macrophage
      receptor with collagenous structure) plays an essential role in the inflammatory
      response of host defense mechanisms and neurodegenerative disorders such as
      Alzheimer's disease. We therefore analyzed the involvement of FPRL1 and MARCO in
      amyloid beta1-42 (Abeta1-42)-induced signalling by extracellular-signal regulated
      kinases 1/2 (ERK1/2) phosphorylation and cAMP level measurement in glial cells
      (astrocytes and microglia) and in transfected HEK293 cells. Receptors were
      inhibited by small interference RNA and the consequences in Abeta1-42- and MARCO
      agonist fucoidan-induced signal transduction were determined. Receptor
      deactivation by antagonists or small interference RNA verified the importance of
      FPRL1 for Abeta1-42-mediated signal transduction by ERK1/2 phosphorylation and
      cAMP level measurement in glial cells. Furthermore, for the first time, we have
      demonstrated a functional interaction between FPRL1 and scavenger receptors in
      fucoidan-mediated signalling by ERK1/2 phosphorylation and cAMP level
      measurement. In addition, co-immunoprecipitation data and fluorescence microscopy
      measurements revealed a physical interaction between FPR, FPRL1 and MARCO. These
      results suggest that FPRL1 plays a pivotal role for Abeta1-42-induced signal
      transduction in glial cells and the interaction with MARCO could explain the
      broad ligand spectrum of formyl peptide receptors.

PMID- 20141571
TI  - Oxytocin signal and social behaviour: comparison among adult and infant oxytocin,
      oxytocin receptor and CD38 gene knockout mice.
AB  - Oxytocin in the hypothalamus is the biological basis of social recognition,
      trust, love and bonding. Previously, we showed that CD38, a proliferation marker
      in leukaemia cells, plays an important role in the hypothalamus in the process of
      oxytocin release in adult mice. Disruption of Cd38 (Cd38 (-/-)) elicited
      impairment of maternal behaviour and male social recognition in adult mice,
      similar to the behaviour observed in Oxt and oxytocin receptor (Oxtr) gene
      knockout (Oxt (-/-) and Oxtr (-/-), respectively) mice. Locomotor activity
      induced by separation from the dam was higher and the number of ultrasonic
      vocalisation calls was lower in Cd38 (-/-) than Cd38( +/+) pups. However, these
      behavioural changes were much milder than those observed in Oxt (-/-) and Oxtr (
      /-) mice, indicating less impairment of social behaviour in Cd38 (-/-) pups.
      These phenotypes appeared to be caused by the high plasma oxytocin levels during
      development from the neonatal period to 3-week-old juvenile mice. ADP-ribosyl
      cyclase activity was markedly lower in the knockout mice from birth, suggesting
      that weaning for mice is a critical time window of plasma oxytocin
      differentiation. Breastfeeding was an important exogenous source of plasma
      oxytocin regulation before weaning as a result of the presence of oxytocin in
      milk and the dam's mammary glands. The dissimilarity between Cd38 (-/-) infant
      behaviour and those of Oxt (-/-) or Oxtr (-/-) mice can be explained partly by
      this exogenous source of oxytocin. These results suggest that secretion of
      oxytocin into the brain in a CD38-dependent manner may play an important role in
      the development of social behaviour.

PMID- 20141572
TI  - CD38/cyclic ADP-ribose system: a new player for oxytocin secretion and regulation
      of social behaviour.
AB  - Oxytocin is important for regulating a number of physiological processes.
      Disruption of the secretion, metabolism or action of oxytocin results in an
      impairment of reproductive function, social and sexual behaviours, and stress
      responses. This review discusses current views on the regulation and
      autoregulation of oxytocin release in the hypothalamic-neurohypophysial system,
      with special focus on the activity of the CD38/cADP-ribose system as a new
      component in this regulation. Data from our laboratories indicate that an
      impairment of this system results in alterations of oxytocin secretion and
      abnormal social behaviour, thus suggesting new clues that help in our
      understanding of the pathogenesis of neurodevelopmental disorders.

PMID- 20141573
TI  - Expression of a Rho guanine nucleotide exchange factor, Ect2, in the developing
      mouse pituitary.
AB  - The pituitary gland is a highly mitotically active tissue after birth. Various
      cell types are known to undergo proliferation in the anterior pituitary. However,
      little is known about the mechanisms regulating mitotic activity in this tissue.
      When searching for genes specifically expressed in the pituitary gland among
      those that we previously screened in Drosophila, we found epithelial cell
      transforming gene 2 (Ect2). Ect2 is a guanine nucleotide exchange factor for Rho
      GTPases, which is known to play an essential role in cytokinesis. Although there
      have been many cellular studies regarding the function of Ect2, the temporal and
      spatial expression patterns of Ect2 in vivo have not been determined. In the
      present study, we examined the postnatal developmental expression of Ect2 in the
      mouse pituitary. Enhanced Ect2 expression was detected in the mouse pituitary
      gland during the first 3 weeks after birth, which coincided well with the period
      of rapid pituitary expansion associated with increased growth rate.
      Immunostaining analysis showed that Ect2-expressing cells were distributed in the
      anterior and intermediate lobes, but not the posterior lobe, of the pituitary.
      These Ect2-expressing cells frequently incorporated the thymidine analogue, EdU
      (5-ethynyl-2'-deoxyuridine), indicating that these cells were mitotically active.
      Taken together, the results demonstrate the functional role of Ect2 in postnatal
      proliferating cells in the two lobes of the pituitary, thereby suggesting roles
      in developmental growth of the mammalian pituitary.

PMID- 20141574
TI  - Three-dimensional digital subtraction angiography in evaluation of
      vertebrobasilar artery dissections: comparison with 2D DSA.

PMID- 20141575
TI  - Maspin expression in head and neck carcinoma: subcellular localization matters.

PMID- 20141576
TI  - Reduced dietary intake of vitamin B12 and folate in patients with recurrent
      aphthous stomatitis.
AB  - BACKGROUND: Recurrent aphthous stomatitis (RAS), commonly referred to as canker
      sores, is a very common and painful oral mucosal disease. Although the etiology
      of RAS is not well understood, a number of factors may play a role, including
      nutritional deficiencies. The objective of this study was to compare dietary
      vitamin intake in RAS patients to that of a control group. METHODS: One hundred
      subjects, who had suffered at least three episodes of minor RAS in the previous
      12 months, completed a detailed Diet History Questionnaire designed and validated
      by the US National Institutes of Health. DietCalc software was used to calculate
      daily dietary intakes of nine different vitamins in the study subjects. Daily
      intakes were energy-adjusted and compared to age- and gender-matched nutrient
      intake data on 9033 subjects from the US National Health and Nutrition
      Examination Survey. RESULTS: The study subjects had significantly lower daily
      intake of vitamin B12 (P < 0.0002) and folate (P < 0.0001) as compared to the
      controls. CONCLUSIONS: Our results demonstrate that patients with recurrent
      aphthous stomatitis are more likely to have lower dietary intakes of vitamin B12
      and folate than a control group. These results support and extend previous
      studies indicating a link between the etiology of RAS and hematological
      deficiencies of vitamin B12 and folate. These findings suggest that consuming
      sufficient amounts of these vitamins may be a useful strategy to reduce the
      number and/or duration of RAS episodes.

PMID- 20141577
TI  - Class II beta-tubulin is a novel marker for human tonsillar M cells and
      follicular dendritic cells.
AB  - OBJECTIVE: Membranous (M) cell of the human palatine tonsil is an antigen entry
      site for mucosal infection, but its location is obscure in histological sections.
      Recently, a microarray analysis has demonstrated that clusterin, annexin A5,
      CD44, MMP14, and beta-tubulin are candidate genes of M cell marker in mice. Among
      these genes, we here describe class II beta-tubulin as a new marker for human
      tonsillar M cells and follicular dendritic cells (FDCs), and present its
      usefulness for diagnosis of angioimmunoblastic T-cell lymphomas (AILTs).
      MATERIALS AND METHODS: Immunohistochemistry and Western blotting for class II
      beta-tubulin were performed using 81 cases of lymphoid, gastrointestinal and
      thyroid tissues, and an FDC cell line, respectively. Double immunostaining with
      clusterin and class II beta-tubulin were carried out. RESULTS: Class II beta
      tubulin localized the M cells and FDCs in the palatine tonsils (10/10, 100%) and
      adenoids (10/10, 100%). It was colocalized with clusterin in the palatine
      tonsils. However, class II beta-tubulin staining did not identify intestinal M
      cells in the intestines. Immunoblot analysis revealed that class II beta-tubulin
      expression was upregulated in HK cells, a normal FDC cell line. Class II beta
      tubulin immunostaining highlighted hyperplastic FDC meshworks in all AILTs
      (14/14, 100%). CONCLUSION: Class II beta-tubulin is a specific histochemical
      marker for human tonsillar M cells and FDCs. Thus, class II beta-tubulin
      immunostaining may be useful to identify tonsillar M cells and to diagnose FDC
      proliferative lesions such as AILT.

PMID- 20141578
TI  - HLA-DRB1*11: a strong risk factor for acquired severe ADAMTS13 deficiency-related
      idiopathic thrombotic thrombocytopenic purpura in Caucasians.

PMID- 20141579
TI  - Accuracy of diagnostic tests for clinically suspected upper extremity deep vein
      thrombosis: a systematic review.
AB  - BACKGROUND: The best available test for the diagnosis of upper extremity deep
      venous thrombosis (UEDVT) is contrast venography. The aim of this systematic
      review was to assess whether the diagnostic accuracy of other tests for
      clinically suspected UEDVT is high enough to justify their use in clinical
      practise and to evaluate if any test can replace venography. METHODS: MEDLINE and
      EMBASE databases were searched from inception to June 2009. Two reviewers
      independently evaluated study eligibility, extracted data, and assessed study
      quality. RESULTS: We identified 17 papers, reporting on 793 patients. Overall,
      the methodological quality was poor, sample sizes were small, and large between
      study differences were observed in spectrum and design. The summary estimates of
      sensitivity (95% confidence interval) were 97% (90-100%) for compression
      ultrasonography, 84% (72-97%) for Doppler ultrasonography, 91% (85-97%) for
      Doppler ultrasonography with compression, and 85% (72-99%) for phleboreography.
      The corresponding summary estimates of specificity were, respectively, 96% (87
      100%), 94% (86-100%), 93% (80-100%), and 87% (71-100%). Clinical findings, a
      clinical score, D-dimer, magnetic resonance imaging, rheography and
      plethysmography were evaluated in one study each, involving a median number of 46
      patients (range 21-214). Sensitivity and specificity ranged from 0% to 100% and
      from 14% to 100%. CONCLUSIONS: Methodological limitations, large between-study
      differences and small sample sizes limit the evidence of tests for clinically
      suspected UEDVT. Compression ultrasonography may be an acceptable alternative to
      venography. The addition of (color) Doppler does not seem to improve the
      accuracy. Adequately designed studies are warranted to confirm these findings.

PMID- 20141580
TI  - Paternal endothelial protein C receptor 219Gly variant as a mild and limited risk
      factor for deep vein thrombosis during pregnancy.
AB  - BACKGROUND: Half of all venous thromboembolism (VTE) cases during pregnancy are
      associated with a maternal thrombophilia. The influence of paternal genotype on
      the placenta and in the genesis of VTE has not been described. OBJECTIVES: To
      determine if the maternal and paternal Ser219Gly dimorphism of the endothelial
      protein C receptor (EPCR), evaluated through detection of the PROCR 6936G allele,
      is a risk factor for VTE during pregnancy. METHODS: Using a case-control study
      nested in the NOHA first cohort of primigravidae, 66 patient couples with a first
      episode of gestational VTE and randomly selected non-thrombotic control couples
      were investigated. For each couple, factor V gene (F5) G1691A, factor II gene
      (F2) G20210A, factor XII gene (F12) C46T and PROCR A6936G polymorphisms were
      determined. RESULTS: Only maternal F5 1691A, F2 20210A and F12 46T alleles were
      independently associated with iliac and infra-iliac deep vein thromboses (DVT).
      The maternal PROCR 6936G allele was a mild risk factor for iliac DVT (OR = 5.5
      [2.3-13.0]). The paternal PROCR 6936G allele was also a mild independent risk
      factor for iliac DVT (OR = 2.6 [1.1-6.2]) and only during pregnancy (rather than
      postpartum) among maternal carriers of the F5 1691A allele (OR = 77.6 [4.2 to >
      999.9]). CONCLUSIONS: The paternal PROCR 6936G allele could be a risk factor for
      maternal iliac DVT. Its impact was milder than the F5 1691A and F2 20210A
      polymorphisms in mothers. We hypothesize that the prothrombotic effect of the
      paternal PROCR 6936G allele is localized. Therefore, DVT during pregnancy may be
      influenced by trophoblastic cell-surface proteins inherited from both maternal
      and paternal alleles.

PMID- 20141581
TI  - Female sexual abuse evaluation in the urological practice: results of a Dutch
      survey.
AB  - INTRODUCTION: There is a strong association between urological complaints and a
      history of sexual abuse, especially in females. It is not known whether
      urologists integrate these facts in their daily practice. AIM: To evaluate
      whether Dutch urologists address the issues of sexual abuse in their female
      patients and to evaluate their perception of sexual abuse prevalences. METHODS: A
      five-item anonymous questionnaire was mailed to all 405 registered members of the
      Dutch Urology Association (urologists and residents). MAIN OUTCOME MEASURES: The
      results of the survey. RESULTS: One hundred eighty-six surveys of eligible
      respondents were returned (45.9% response rate). A total of 68.8% stated that
      they always ask their female patients about sexual abuse before doing the
      physical examination. Overall, 79.3% said to do so when a patient has certain
      urological complaints: 77.6% in case of lower abdominal pain, 62.1% in urgency or
      frequency, 41.4% in incontinence, 29.3% in urinary tract infections, and 3.4% in
      hematuria. The majority of the respondents (74.3%) estimated the frequency of
      sexual abuse in their urological clinic to be equal or less than 10%. CONCLUSION:
      Nearly 70% of the responding Dutch urologists and residents ask their female
      patients about possible sexual abuse. They estimate the frequency of sexual abuse
      in their female patients to be equal or less than 10%.

PMID- 20141583
TI  - Effects of Korean red ginseng on sexual arousal in menopausal women: placebo
      controlled, double-blind crossover clinical study.
AB  - INTRODUCTION: Many menopausal women experience climacteric symptoms including
      impairment of sexual function. Recent reports have suggested that Korean red
      ginseng (KRG) has a relaxing effect on the clitoral cavernosal muscle and vaginal
      smooth muscle in rats. AIM: We assessed whether KRG extracts would improve sexual
      function in menopausal women. METHODS: Thirty-two menopausal women participated
      in a placebo-controlled, double-blind, crossover clinical study with
      administration of either three capsules of ginseng (1 g per capsule) or placebo
      daily. After completing the KRG or placebo arm, the participants were crossed
      over to the other arm after a 2-week washout period. The efficacy and safety of
      the KRG extracts were measured by using questionnaires. MAIN OUTCOME MEASURES:
      Female Sexual Function Index (FSFI) and Global Assessment Questionnaire (GAQ).
      RESULTS: Twenty-eight women completed the study. They were, on average, 51.2 + or
      - 4.1 years old, and their mean menopausal state was for a duration of 37.4 + or 
      2.9 months. Few carryover effects were noted in either study arm. The ginseng
      extract significantly improved scores on the FSFI from 3.10 + or - 0.87 to 3.50 +
      or - 0.72 in the sexual arousal domain (P = 0.006). The GAQ was more
      significantly affected by ginseng extracts than by placebo (P = 0.046). There
      were no severe adverse events in the KRG group, although two cases of vaginal
      bleeding occurred during KRG treatment. CONCLUSIONS: Oral administration of KRG
      extracts improved sexual arousal in menopausal women. Red ginseng extracts might
      be used as an alternative medicine in menopausal women to improve their sexual
      life.

PMID- 20141582
TI  - Ontogenetic profile of the expression of thyroid hormone receptors in rat and
      human corpora cavernosa of the penis.
AB  - INTRODUCTION: In the last few years, various studies have underlined a
      correlation between thyroid function and male sexual function, hypothesizing a
      direct action of thyroid hormones on the penis. AIM: To study the spatiotemporal
      distribution of mRNA for the thyroid hormone nuclear receptors (TR) alpha1,
      alpha2 and beta in the penis and smooth muscle cells (SMCs) of the corpora
      cavernosa of rats and humans during development. METHODS: We used several
      molecular biology techniques to study the TR expression in whole tissues or
      primary cultures from human and rodent penile tissues of different ages. MAIN
      OUTCOME MEASURE: We measured our data by semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) amplification, Northern blot and
      immunohistochemistry. RESULTS: We found that TRalpha1 and TRalpha2 are both
      expressed in the penis and in SMCs during ontogenesis without development
      dependent changes. However, in the rodent model, TRbeta shows an increase from 3
      to 6 days post natum (dpn) to 20 dpn, remaining high in adulthood. The same
      expression profile was observed in humans. While the expression of TRbeta is
      strictly regulated by development, TRalpha1 is the principal isoform present in
      corpora cavernosa, suggesting its importance in SMC function. These results have
      been confirmed by immunohistochemistry localization in SMCs and endothelial cells
      of the corpora cavernosa. CONCLUSIONS: The presence of TRs in the penis provides
      the biological basis for the direct action of thyroid hormones on this organ.
      Given this evidence, physicians would be advised to investigate sexual function
      in men with thyroid disorders.

PMID- 20141584
TI  - Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat
      weed (Epimedium spp.) in vitro and in vivo.
AB  - INTRODUCTION: Epimedium species (aka horny goat weed) have been utilized for the
      treatment of erectile dysfunction in Traditional Chinese Medicine for many years.
      Icariin (ICA) is the active moiety of Epimedium species. AIM: To evaluate the
      penile hemodynamic and tissue effects of ICA in cavernous nerve injured rats. We
      also studied the in vitro effects of ICA on cultured pelvic ganglia. METHODS:
      Rats were subjected to cavernous nerve injury and subsequently treated for 4
      weeks with daily gavage feedings of a placebo solution of normal saline and
      Dimethyl sulfoxide (DMSO) vs. ICA dissolved in DMSO at doses of 1, 5, and 10
      mg/kg. A separate group underwent a single dose of ICA 10 mg/kg 2 hours prior to
      functional testing. Functional testing with cavernous nerve stimulation and real
      time assessment of intracavernous pressure (ICP) was performed at 4 weeks. After
      functional testing, penile tissue was procured for immunohistochemistry and
      molecular studies. In separate experiments, pelvic ganglia were excised from
      healthy rats and cultured in the presence of ICA, sildenafil, or placebo culture
      media. MAIN OUTCOME MEASURE: Ratio of ICP and area under the curve (AUC) to mean
      arterial pressure (MAP) during cavernous nerve stimulation of subject rodents. We
      also assayed tissue expression of neuronal nitric oxide synthase (nNOS), eNOS:
      endothelial nitric oxide synthase (eNOS), calponin, and apoptosis via
      immunohistochemistry and Western blot. Serum testosterone and luteinizing hormone
      (LH) were assayed using enzyme-linked immunosorbant assay (ELISA). Differential
      length of neurite outgrowth was assessed in cultured pelvic ganglia. RESULTS:
      Rats treated with low-dose ICA demonstrated significantly higher ICP/MAP and
      AUC/MAP ratios compared with control and single-dose ICA animals.
      Immunohistochemistry and Western blot were revealing of significantly greater
      positivity for nNOS and calponin in penile tissues of all rats treated with ICA.
      ICA led to significantly greater neurite length in cultured specimens of pelvic
      ganglia. CONCLUSION: ICA may have neurotrophic effects in addition to known
      phosphodiesterase type 5 inhibiting effects.

PMID- 20141585
TI  - The effect of statin therapy on testosterone levels in subjects consulting for
      erectile dysfunction.
AB  - INTRODUCTION: Previous clinical studies on effect of statins treatment on
      testosterone (T) levels have produced mixed results. AIM: The aim of the present
      study is to evaluate the association between statin therapy and hormonal
      parameters in a large series of subjects seeking medical care at our unit for
      erectile dysfunction (ED). METHODS: A consecutive series of 3,484 (mean age 51.6
      + or - 13.1 years) patients with ED was studied. MAIN OUTCOME MEASURES: Several
      hormonal and biochemical parameters were investigated, along with ANDROTEST
      structured interview measuring hypogonadism-related symptoms. RESULTS: Among the
      patients studied, 244 (7%) patients were being treated with statins. After
      adjustment for confounding factors (including body mass index and Progetto Cuore
      cardiovascular (CV) risk engine score), both total and calculated free
      testosterone levels were significantly lower in subjects taking statins, when
      compared to the rest of the sample (hazard ratio [HR] = 0.93 [0.90; 0.96] and
      0.26 [0.01; 0.18] for each decrement of total T and calculated free T,
      respectively; both P < 0.0001). The use of statins was also associated with a
      reduced testis volume and a higher prevalence of hypogonadism-related symptoms
      and signs, as assessed by higher ANDROTEST score (HR = 1.12 [1.03; 1.21]; P <
      0.01 after adjustment for confounders). Follicle-stimulating hormone levels were
      significantly higher in subjects treated with statins when compared to the rest
      of the sample, while there was a trend toward higher luteinizing hormone levels,
      but this did not reach statistical significance. The lower levels of total and
      calculated free T observed in subjects treated with statins were also confirmed
      comparing them with age-waist circumference and CV risk score matched controls.
      Finally, subjects being treated with statins showed lower prolactin levels when
      compared to the rest of the sample. CONCLUSIONS: Our data demonstrated that
      statin therapy might induce an overt primary hypogonadism and should be
      considered as a possible confounding factor for the evaluation of testosterone
      levels in patients with ED.

PMID- 20141587
TI  - The dopamine transporter gene (DAT1) polymorphism is associated with premature
      ejaculation.
AB  - INTRODUCTION: Previous research has suggested brain dopamine (DA)
      neurotransmission to be involved in the control of ejaculation. Furthermore,
      previous studies indicate a partly hereditary background to premature
      ejaculation. AIM: To investigate whether the dopamine transporter gene (DAT1)
      polymorphism is associated with premature ejaculation. METHODS: Retrospective
      self-reports of four indicators reflecting ejaculatory function-anteportal
      ejaculation, number of penile thrusts, ejaculation latency time, and feeling of
      control over ejaculation-and saliva samples for DNA analysis were obtained from
      1,290 men (M = 26.9, standard deviation = 4.7 years; range 18-45) with sexual
      experience. Main Outcome Measures. Calculations of allelic effects were computed
      using the Generalized Estimating Equations module of SPSS 17. RESULTS: Carriers
      of the 10R10R genotype had scores indicating a lower threshold to ejaculate on
      each of the indicators compared to the combined 9R9R/9R10R carrier group. The
      differences were significant both for the composite score and for anteportal
      ejaculation, number of thrusts, and feeling of control over ejaculation, but not
      for ejaculation latency time. The effect of the polymorphism remained significant
      after controlling for age, homosexual experience, having a regular sexual
      partner, level of sexual desire, and frequency of sexual activity, hence
      suggesting that it is not secondary to an association between the studied
      polymorphism and some other aspect of sexual behavior, but due to a specific
      influence of DA on ejaculation. CONCLUSIONS: The findings of the present study
      support results of previous studies indicating involvement of dopaminergic
      neurotransmission in ejaculation.

PMID- 20141586
TI  - The effect of intracavernous injection of adipose tissue-derived stem cells on
      hyperlipidemia-associated erectile dysfunction in a rat model.
AB  - INTRODUCTION: Hyperlipidemia has been associated with erectile dysfunction (ED)
      via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem
      cells (ADSC) have been shown to differentiate into endothelial cells and secrete
      vasculotrophic and neurotrophic factors. AIM: To assess whether ADSC have
      therapeutic effects on hyperlipidemia-associated ED. METHODS: Twenty-eight male
      rats were induced to develop hyperlipidemia with a high-fat diet (hyperlipidemic
      rats, HR). Ten additional male rats were fed a normal diet to serve as controls
      (normal rats, NR). Five months later, all rats were subjected to ADSC isolation
      from paragonadal fat. The cells were cultured for 1 week, labeled with 5-ethynyl
      2'-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum
      of 18 HR. The remaining 10 HR rats were injected with phosphate buffered saline
      (PBS). At 2 and 14 days post-transplantation, four rats in the HR + ADSC group
      were sacrificed for tracking of the transplanted cells. At 28 days post
      transplantation, all remaining rats were analyzed for serum biochemistry,
      erectile function, and penile histology. MAIN OUTCOME MEASURES: Erectile function
      was assessed by intracavernous pressure (ICP) measurement during
      electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and
      smooth muscle were assessed by immunohistochemistry. RESULTS: Serum total
      cholesterol and low-density lipoprotein levels were significantly higher in HR
      than in NR. High-density lipoprotein level was significantly lower in HR than in
      NR. Mean ICP/mean arterial pressure ratio was significantly lower in HR + PBS
      than in NR + PBS or HR + ADSC. Neuronal nitric oxide synthase (nNOS)-positive
      nerve fibers and endothelial cells were fewer in HR + PBS than in HR + ADSC.
      Smooth muscle content was significantly higher in both HR groups than in NR.
      CONCLUSIONS: Hyperlipidemia is associated with abnormalities in both the nerves
      and endothelium. Treatment with ADSC ameliorates these adverse effects and holds
      promise as a potential new therapy for ED.

PMID- 20141588
TI  - Study of the prevalence of female sexual dysfunction in sexually active women 18
      to 40 years of age in Medellin, Colombia.
AB  - INTRODUCTION: The prevalence of female sexual dysfunction (FSD) in Colombia has
      not been adequately studied. A reliable estimate of the prevalence of FSD can be
      helpful for the adequate planning of reproductive health and research activities.
      AIM: Measure the prevalence of female sexual complaints in a sample of sexually
      active women aged 18-40 years in a city of Colombia. METHODS: A self-administered
      validated questionnaire, the Female Sexual Function Index (FSFI), was
      administered to 410 sexually active women at different focal groups. A cutoff
      value of 26.5 was used to define female sexual complaint. Ten questions on age,
      educational level, socioeconomic status, marital status, cohabitation, depressive
      feelings, use of antidepressive drugs, menstrual cycle, offspring, and
      contraception were included. MAIN OUTCOME MEASURES: The primary end point was the
      percentage of women having a score equal or less than 26.5. RESULTS: In the study
      group, 117 of 391 women scored less than 26.5 for a prevalence of sexual
      complaints of 30%. The independent variables associated with sexual complaints
      were low educational level, the feelings of depression, and the use of
      antidepressive drugs. CONCLUSION: The present study found a low FSFI score in 30%
      of sexually active women aged 18-40 years in the city of Medellin, Colombia,
      which could be indicative of sexual complaints.

PMID- 20141589
TI  - Prevalence of undiagnosed testosterone deficiency in aging athletes: does
      exercise training influence the symptoms of male hypogonadism?
AB  - INTRODUCTION: Worldwide many aging males practice sports. A high prevalence of
      late-onset male hypogonadism has been observed in general population. Sport
      participation influences the neuroendocrine system and may decrease serum
      testosterone. AIM: This preliminary study was designed to estimate the prevalence
      and the symptoms of undiagnosed testosterone deficiency in aging athletes.
      METHODS: This observational survey was performed in 183 caucasian male athletes
      >50 years, in the setting of pre-participation screening. Pituitary-gonadal
      hormones and symptoms of hypogonadism were investigated. Serum total testosterone
      (TT), sex hormone binding globulin, luteinizing hormone (LH), follicle
      stimulating hormone (FSH), prolactin (PRL), free-T4, and thyroid stimulation
      hormone (TSH) were assayed, and free T, bioactive T, and the LH/TT ratio were
      calculated. The International Index of Erectile Dysfunction (IIEF-15) and the
      Center for Epidemiological Studies Depression Scale (CES-D) were administered.
      Hypogonadal athletes were compared with eugonadal athletes as controls. MAIN
      OUTCOME MEASURES: Prevalence and clinical symptoms of severe (TT < 8 nmol/L) or
      mild (8 nmol/L <or= TT < 12 nmol/L) testosterone deficiency were investigated.
      RESULTS: The mean sample age was 61.9 +/- 7.5 years (range 50-75). Severe or mild
      testosterone deficiency was observed in 12% and 18%, respectively, of overall
      athletes, with the highest prevalence in athletes >70 years (27.5% and 25.0%,
      respectively). TT did not correlate with age, training duration, or questionnaire
      scores. No differences were observed for nonspecific symptoms of hypogonadism,
      IIEF-15 and CES-D scores between eugonadal and severe hypogonadal athletes.
      CONCLUSIONS: Independently of its etiology, a significant percentage of aging
      athletes had undiagnosed testosterone deficiency. In a relevant number of these
      cases, testosterone deficiency was not overtly symptomatic. Our results suggest
      that sport-participation per se can influence the symptoms of hypogonadism. The
      history of clinical symptoms may be inaccurate to diagnose testosterone
      deficiency in aging athletes. Future research should address the clinical
      relevance and the specific risks of testosterone deficiency in aging athletes,
      and the need of a systematic pre-participation serum testosterone evaluation.

PMID- 20141590
TI  - Women's motivations for sex: exploring the diagnostic and statistical manual,
      fourth edition, text revision criteria for hypoactive sexual desire and female
      sexual arousal disorders.
AB  - INTRODUCTION: There are problems with the existing definition of hypoactive
      sexual desire disorder (HSDD) in that desire for sex and sexual fantasy are not a
      universal experience. AIMS: To explore: (i) women's motivations to engage in
      sexual activity; (ii) frequency and predictors of sexual fantasies; (iii) sexual
      arousal; (iv) recognition of sexual arousal; and (v) association between
      relationship duration and these variables. METHODS: Three thousand six hundred
      eighty-seven women completed a web-based survey of previously pilot-tested items.
      MAIN OUTCOME MEASURES: Investigator-derived self-report questions of sexual
      desire and arousal, and sexual fantasies. RESULTS: Among women who easily became
      aroused, 15.5% reported only engaging in sex if they felt sexual desire at the
      outset whereas 30.7% typically or always accessed desire only once they were
      aroused. Women in longer-term relationships engaged in sex with no sexual desire
      more often (42%) than women in short-term relationships (22.4%) (P < 0.001). The
      percentage of women that reported fantasies only sometimes was 52.5%. A logistic
      regression revealed that religion (odds ratio [OR] = 1.45; P < 0.001), difficulty
      getting aroused (OR = 0.511; P < 0.001), responsive desire (OR = 0.919; P <
      0.05), and frequency of orgasm (OR = 1.11; P < 0.05) were significantly
      associated with sexual fantasy. After controlling for age, relationship duration
      was negatively associated with frequency of initiating sex (r = -0.116, P <
      0.001), women's satisfaction with their own sexuality (r = -0.173, P < 0.001) and
      sexual satisfaction with the partner (r = -0.162, P < 0.001). CONCLUSIONS:
      Results reflect diversity in women's motivations for sex, and there is evidence
      that responsive desire occurs in women with and without arousal difficulties. We
      strongly recommend relationship duration as well as adequacy of partner sexual
      stimulation to be recognized in any future diagnostic framework of dysfunction.
      Clinical implications as well as those for future diagnostic nomenclature are
      considered.

PMID- 20141591
TI  - MLST and a genetic study of antibiotic resistance and virulence factors in vanA
      containing Enterococcus from buzzards (Buteo buteo).
AB  - AIMS: To analyse the occurrence of faecal carriage of vancomycin-resistant
      enterococci (VRE) in Buteo buteo and to study the associated resistance and
      virulence genes. METHODS AND RESULTS: The presence of VRE was investigated in 33
      faecal samples of B. buteo. Samples were seeded in Slanetz-Bartley agar plates
      supplemented with vancomycin for VRE recovery. Genes encoding antimicrobial
      resistance and virulence were studied by polymerase chain reaction. Vancomycin
      resistant Enterococcus faecium isolates were characterized by multilocus sequence
      typing. VRE with an acquired mechanism of resistance (vanA genotype) were
      detected in 9% of samples analysed (Ent. faecium and Enterococcus durans). In
      addition, 27% of samples contained VRE with an intrinsic mechanism of resistance
      (Enterococcus gallinarum, vanC1). All vanA-containing isolates showed resistance
      to tetracycline and erythromycin and harboured the tet(M) and/or tet(L) genes, in
      addition to the ermB gene. The vat(E) and/or vat(D), cat(A) and aph(3')-IIIa
      genes were identified in quinupristin-dalfopristin-, chloramphenicol-, and
      kanamycin-resistant vanA-containing strains, respectively. The sequence types
      ST273 and ST5 were identified in two vanA-positive Ent. faecium isolates, and the
      presence of hyl, gelE, cylA, cylL and cylM virulence genes and gelatinase
      activity were identified in Ent. faecium ST5 strain. CONCLUSIONS: The intestinal
      tract of B. buteo could be a reservoir of vanA-positive enterococci. SIGNIFICANCE
      AND IMPACT OF THE STUDY: First study focused to define the occurrence of vanA
      containing Enterococcus strains in B. buteo.

PMID- 20141592
TI  - Is the hepatitis C virus epidemic over in Egypt? Incidence and risk factors of
      new hepatitis C virus infections.
AB  - OBJECTIVES: To estimate hepatitis C virus (HCV) incidence rates and identify risk
      factors for current HCV transmission with emphasis on the role of living with
      infected household family members in rural Egypt. METHODS: A 4-year population
      based, cohort study of seronegative villagers was conducted to identify incident
      HCV seroconversion cases. A risk factor questionnaire and blood samples for anti
      HCV EIA-3 and HCV RNA polymerase chain reaction testing were collected at two
      rounds of follow-up. Incidence rates, relative risks and 95% confidence interval
      (CI) were calculated based on a Poisson distribution. A matched case-control
      analysis to explore specific behavioural predictors of infection was conducted
      and odds ratios were obtained by conditional logistic regression. RESULTS: Twenty
      five participants (11 females) seroconverted in 10,578 person years of follow-up
      (PY), (incidence rate of 2.4/1000 PY; 95% CI: 1.6-3.5). The median age at
      seroconversion was 26 years [interquartile range (IQR) 19-35] among males and 20
      years (IQR 13-24) among females. The only significant risk factor identified for
      these cases was receiving injections [adjusted odds ratio (OR(adj))=3.3; 95% CI:
      1.1-9.8]. Two of the 17 viraemic seroconvertors were infected with the same
      strain as at least one of their family members. CONCLUSION: This study identified
      the important role of injections in spreading HCV infection in this rural
      community. National healthcare awareness and infection control programmes should
      be strengthened to prevent further transmission. Screening of families of
      infected HCV subjects should be an essential part of case management for early
      detection and management.

PMID- 20141593
TI  - Multicentric evaluation of a clinical and prognostic scoring system predictive of
      survival after resection of intrahepatic cholangiocarcinomas.
AB  - OBJECTIVE: To develop a clinical and prognostic scoring system predictive of
      survival after resection of intrahepatic cholangiocarcinomas (ICC). PATIENTS: Two
      hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New
      York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing
      the data set from Essen University and then applied to the data sets from Mount
      Sinai Medical Center and Chiba University for validation. Eighteen potential
      prognostic factors were evaluated. Statistical analysis included multivariable
      regression analyses with the Cox proportional hazard model, power analysis,
      internal validation with structural equation modelling bootstrapping and external
      validation. The prognostic scoring model was based mainly in pathological and
      demographical variables, whereas the clinical scoring model was based mainly in
      radiological and demographical variables. RESULTS: Gender (P=0.0086), UICC stage
      (P=0.0140) and R-class (P=0.0016) were predictive of survival for the prognostic
      scoring model, while gender (P=0.0023), CA 19-9 levels (P=0.0153) and
      macrovascular invasion (P=0.0067) were predictive of survival for the clinical
      scoring model. Prognostic points were assigned as follows: female:male=1:2
      points, UICC (I-II):UICC (III-IV)=1:2 points and R0:R1=1:2 points. Clinical
      points were allocated as follows: female:male=1:2 points, CA 19-9 (<100 U/ml):CA
      19-9 (> or =100 U/ml)=1:2 points and no macrovascular invasion:macrovascular
      invasion=1:2 points. Prognostic groups with 3-4, 5 and 6 points (P=0.000001) and
      clinical groups with 3-4 and 5-6 points (P=0.0103) achieved statistically
      significant difference. CONCLUSIONS: We propose a clinical and prognostic scoring
      system predictive of long-term survival after surgical resections for ICC.

PMID- 20141594
TI  - Population structuring of the tsetse Glossina tachinoides resulting from
      landscape fragmentation in the Mouhoun River basin, Burkina Faso.
AB  - The impact of landscape fragmentation resulting from human- and climate-mediated
      factors on the structure of a population of Glossina tachinoides Westwood
      (Diptera: Glossinidae) in the Mouhoun River basin, Burkina Faso, was
      investigated. Allele frequencies at five microsatellite loci were compared in
      four populations. The average distance between samples was 72 km. The sampling
      points traversed an ecological cline in terms of rainfall and riverine forest
      ecotype, along a river loop that enlarged from upstream to downstream.
      Microsatellite DNA demonstrated no structuring among the groups studied (F(ST) =
      0.015, P = 0.07), which is contrary to findings pertaining to Glossina palpalis
      gambiensis Vanderplank in the same geographical area. The populations of G.
      tachinoides showed complete panmixia (F(IS) = 0, P = 0.5 for the whole sample)
      and no genetic differentiation among populations or global positioning system
      trap locations. This is in line with the results of dispersal studies which
      indicated higher diffusion coefficients for G. tachinoides than for G. p.
      gambiensis. The impact of these findings is discussed within the framework of
      control campaigns currently promoted by the Pan African Tsetse and Trypanosomosis
      Eradication Campaign.

PMID- 20141597
TI  - Retinal arteriolar changes: intermediate pathways linking early life exposures to
      cardiovascular disease?
AB  - Low birth weight is an indicator of exposure to unfavorable fetal environment and
      has been associated with the development of hypertension and cardiovascular
      disease in adulthood. There is now growing evidence suggesting that alterations
      in the microcirculation associated with exposure to a suboptimal in utero
      environment play a key role in the development of cardiovascular disease.
      Proposed hypothetical mechanisms include: fetal circulatory redistribution,
      impaired synthesis of elastin, and endothelial dysfunction in response to
      antenatal and postnatal environment. More recent studies have shown associations
      of low birth weight with capillary rarefaction and narrowing retinal arteriolar
      caliber in both children and adults. This suggests that vascular adaptations in
      utero persist into maladaptive circulatory changes in adulthood, which may
      reflect an increased susceptibility to hypertension and cardiovascular disease
      later in life. Therefore, the association between low birth weight and narrower
      retinal arteriolar caliber, together with associations between narrower retinal
      arteriolar caliber and risk of hypertension and cardiovascular disease, suggest
      that retinal arteriolar narrowing may be a marker on the microvascular pathway
      and mechanisms linking early life exposures and subsequent cardiovascular
      disease.

PMID- 20141596
TI  - Marvels, mysteries, and misconceptions of vascular compensation to peripheral
      artery occlusion.
AB  - Peripheral arterial disease is a major health problem and there is a significant
      need to develop therapies to prevent its progression to claudication and critical
      limb ischemia. Promising results in rodent models of arterial occlusion have
      generally failed to predict clinical success and led to questions of their
      relevance. While sub-optimal models may have contributed to the lack of progress,
      we suggest that advancement has also been hindered by misconceptions of the human
      capacity for compensation and the specific vessels which are of primary
      importance. We present and summarize new and existing data from humans, Ossabaw
      miniature pigs, and rodents which provide compelling evidence that natural
      compensation to occlusion of a major artery (i) may completely restore perfusion,
      (ii) occurs in specific pre-existing small arteries, rather than the distal
      vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii)
      is impaired by cardiovascular risk factors which suppress the flow-mediated
      mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We
      propose that restoration of the capacity for flow-mediated dilation and
      remodeling in small arteries represents a largely unexplored potential
      therapeutic opportunity to enhance compensation for major arterial occlusion and
      prevent the progression to critical limb ischemia in the peripheral circulation.

PMID- 20141598
TI  - Liver sinusoidal endothelial fenestrations in caveolin-1 knockout mice.
AB  - OBJECTIVE: Fenestrations are pores in the liver sinusoidal endothelium that
      facilitate the transfer of particulate substrates between the sinusoidal lumen
      and hepatocytes. Fenestrations express caveolin-1 and have structural
      similarities to caveolae, therefore might be a form of caveolae and caveolin-1
      may be integral to fenestration structure and function. Therefore, fenestrations
      were studied in the livers of caveolin-1 knockout mice. METHODS: Scanning,
      transmission and immunogold electron microscopic techniques were used to study
      the liver sinusoidal endothelium and other tissues in caveolin-1 knockout and
      wild-type mice. RESULTS: Comparison of fenestrations in wild-type and knockout
      mice did not reveal any differences on either scanning or transmission electron
      microscopy. The diameter of the fenestrations was not significantly different (74
      +/- 13 nm knockout mice vs 78 +/- 12 nm wild-type mice) nor was the fenestration
      porosity (6.5 +/- 2.1 knockout vs 7.3 +/- 2.4% wild-type mice). In contrast,
      adipocytes and blood vessels in other tissues lacked caveolae in the knockout
      mice. Caveolin-1 immunogold of livers of wild-type mice indicated sparse
      expression in sinusoidal endothelial cells. CONCLUSIONS: The normal structure of
      fenestrations in the liver sinusoidal endothelium is not dependent upon caveolin
      1 and fenestrations are not a form of caveolae.

PMID- 20141599
TI  - Regulation of cerebromicrovascular permeability by lysophosphatidic acid.
AB  - OBJECTIVE: Lysophosphatidic acid (LPA) increases permeability of cerebral
      endothelium in culture, but it has been suggested that histamine release is
      required in vivo. METHODS: Cerebral venular permeability was measured by using
      the single-vessel micro-occlusion technique, and fura-2 ratios were used to track
      changes in endothelial [Ca(2+)]. RESULTS: Topical acute LPA application dose
      dependently increased permeability (log EC(50)-9.4; similar to the K(d) of the
      LPA1 receptor). The calcium response to LPA was similar to histamine, but the
      permeability response was unaffected by H(2)-histamine receptor antagonism, and
      was blocked by Ki16425, a LPA1 receptor antagonist. The permeability response was
      blocked by nitric oxide synthase and free radical scavenging, which were carried
      out together, but not separately. Intravascular LPA bolus injection increased
      permeability. Whole serum albumin, or plasma albumin co-applied with LPA,
      increased permeability, but less potently than LPA itself (log EC(50) 5.1 and
      6.1, respectively). Tachyphylaxis of the LPA1 receptor was demonstrated by LPA
      application for 10 minutes, which resulted in suppression of the response to
      subsequent applications for the following 15 minutes. CONCLUSIONS:
      Lysophosphatidic acid increases cerebrovascular permeability by acting directly
      on the endothelium and utilizes both nitric oxide and free radical signaling
      pathways.

PMID- 20141600
TI  - Differential impact of familial hypercholesterolemia and combined hyperlipidemia
      on vascular wall and network remodeling in mice.
AB  - Genetic familial hypercholesterolemia (FH) and combined hyperlipidemia (FCH) are
      characterized by elevated plasma low-density lipoprotein (LDL) (FH) and
      LDL/triglycerides (FCH), with mouse models represented by LDL receptor (LDLR) and
      apolipoprotein E (ApoE) gene deletion mice, respectively. Given the impact of FH
      and FCH on health outcomes, we determined the impact of FH/FCH on vascular
      structure in LDLR and ApoE mice. LDLR, ApoE and control mice were utilized at 12
      13 and 22-23 weeks when gracilis arteries were studied for wall mechanics and
      gastrocnemius muscles were harvested for microvessel density measurements.
      Conduit arteries and plasma samples were harvested for biochemical analyses.
      Arteries from ApoE and LDLR exhibited blunted expansion versus control, reduced
      distensibility and left-shifted stress versus strain relation (LDLR > ApoE).
      Microvessel density was reduced in ApoE and LDLR (ApoE > LDLR). Secondary
      analyses suggested that wall remodeling in LDLR was associated with cholesterol
      and MCP-1, while rarefaction in ApoE was associated with tumor necrosis factors
      alpha, triglycerides and vascular production of TxA(2). Remodeling in ApoE and
      LDLR appears distinct; as that in LDLR is preferential for vascular walls, while
      that for ApoE is stronger for rarefaction. Remodeling in LDLR may be associated
      with cellular adhesion, while that in ApoE may be associated with pro-apoptotsis
      and constrictor prostanoid generation.

PMID- 20141601
TI  - Quantitation of microcomputed tomography-imaged ocular microvasculature.
AB  - PURPOSE: To quantitatively assess microvascular dimensions in the eyes of
      neonatal wild-type and VEGF(120)-tg mice, using a novel combination of techniques
      which permit three-dimensional (3D) image reconstruction. METHODS: A novel
      combination of techniques was developed for the accurate 3D imaging of the
      microvasculature and demonstrated on the hyaloid vasculature of the neonatal
      mouse eye. Vascular corrosion casting is used to create a stable replica of the
      vascular network and X-ray microcomputed tomography (muCT) to obtain the 3D
      images. In-house computer-aided image analysis techniques were then used to
      perform a quantitative morphological analysis of the images. RESULTS: With the
      use of these methods, differences in the numbers of vessel segments, their
      diameter, and volume of vessels in the vitreous compartment were quantitated in
      wild-type neonatal mice or littermates over-expressing a labile (nonheparin
      binding) isoform of vascular endothelial growth factor (VEGF(120)) from the
      developing lens. This methodology was instructive in demonstrating that hyaloid
      vascular networks in VEGFA(120) over-expressing mice have a 10-fold increase in
      blind-ended, a six-fold increase in connected vessel segments, in addition to a
      sixfold increase (0.0314 versus 0.0051 mm(3)) in total vitreous vessel volume
      compared with wild type. These parameters are not readily quantified via
      histological, ultrastructural, or stereological analysis. CONCLUSION: The
      combination of techniques described here provides the first 3D quantitative
      characterization of vasculature in an organ system; i.e., the neonatal murine
      intra-ocular vasculature in both wild-type mice and a transgenic model of lens
      specific over-expression of VEGF.

PMID- 20141602
TI  - Local transient myocardial liposomal gene transfer of inducible nitric oxide
      synthase does not aggravate myocardial function and fibrosis and leads to
      moderate neovascularization in chronic myocardial ischemia in pigs.
AB  - BACKGROUND: This study was designed to explore the effect of transient inducible
      nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene
      transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine
      model of chronic ischemia. METHODS AND RESULTS: Chronic myocardial ischemia was
      induced using a minimally invasive model in 23 landrace pigs. Upon demonstration
      of heart failure, 10 animals were treated with liposome-mediated iNOS-gene
      transfer by local intramyocardial injection and 13 animals received a sham
      procedure to serve as control. The efficacy of this iNOS-gene-transfer was
      demonstrated for up to 7 days by reverse transcriptase-polymerase chain reaction
      in preliminary studies. Four weeks after iNOS transfer, magnetic resonance
      imaging showed no effect of iNOS overexpression on cardiac contractility at rest
      and during dobutamine stress (resting ejection fraction: control 27%, iNOS 26%; P
      = ns). Late enhancement, infarct size, and the amount of fibrosis were similar
      between groups. Although perfusion and perfusion reserve in response to adenosine
      and dobutamine were not significantly modified by iNOS-transfer, both vessel
      number and diameter were significantly increased in the ischemic area in the iNOS
      treated group versus control (point score: control 15.3, iNOS 34.7; P < 0.05).
      CONCLUSIONS: Our findings demonstrate that transient iNOS overexpression does not
      aggravate cardiac dysfunction or postischemic fibrosis, while potentially
      contributing to neovascularization in the chronically ischemic heart.

PMID- 20141603
TI  - Forward genetics in Candida albicans that reveals the Arp2/3 complex is required
      for hyphal formation, but not endocytosis.
AB  - Candida albicans is a diploid fungal pathogen lacking a defined complete sexual
      cycle, and thus has been refractory to standard forward genetic analysis.
      Instead, transcription profiling and reverse genetic strategies based on
      Saccharomyces cerevisiae have typically been used to link genes to functions. To
      overcome restrictions inherent in such indirect approaches, we have investigated
      a forward genetic mutagenesis strategy based on the UAU1 technology. We screened
      4700 random insertion mutants for defects in hyphal development and linked two
      new genes (ARP2 and VPS52) to hyphal growth. Deleting ARP2 abolished hyphal
      formation, generated round and swollen yeast phase cells, disrupted cortical
      actin patches and blocked virulence in mice. The mutants also showed a global
      lack of induction of hyphae-specific genes upon the yeast-to-hyphae switch.
      Surprisingly, both arp2 Delta/Delta and arp2 Delta/Delta arp3 Delta/Delta mutants
      were still able to endocytose FM4-64 and Lucifer Yellow, although as shown by
      time-lapse movies internalization of FM4-64 was somewhat delayed in mutant cells.
      Thus the non-essential role of the Arp2/3 complex discovered by forward genetic
      screening in C. albicans showed that uptake of membrane components from the
      plasma membrane to vacuolar structures is not dependent on this actin nucleating
      machinery.

PMID- 20141604
TI  - New insights into the blood-stage transcriptome of Plasmodium falciparum using
      RNA-Seq.
AB  - Recent advances in high-throughput sequencing present a new opportunity to deeply
      probe an organism's transcriptome. In this study, we used Illumina-based
      massively parallel sequencing to gain new insight into the transcriptome (RNA
      Seq) of the human malaria parasite, Plasmodium falciparum. Using data collected
      at seven time points during the intraerythrocytic developmental cycle, we (i)
      detect novel gene transcripts; (ii) correct hundreds of gene models; (iii)
      propose alternative splicing events; and (iv) predict 5' and 3' untranslated
      regions. Approximately 70% of the unique sequencing reads map to previously
      annotated protein-coding genes. The RNA-Seq results greatly improve existing
      annotation of the P. falciparum genome with over 10% of gene models modified. Our
      data confirm 75% of predicted splice sites and identify 202 new splice sites,
      including 84 previously uncharacterized alternative splicing events. We also
      discovered 107 novel transcripts and expression of 38 pseudogenes, with many
      demonstrating differential expression across the developmental time series. Our
      RNA-Seq results correlate well with DNA microarray analysis performed in parallel
      on the same samples, and provide improved resolution over the microarray-based
      method. These data reveal new features of the P. falciparum transcriptional
      landscape and significantly advance our understanding of the parasite's red blood
      cell-stage transcriptome.

PMID- 20141605
TI  - Fermented Maesil (Prunus mume) with probiotics inhibits development of atopic
      dermatitis-like skin lesions in NC/Nga mice.
AB  - Maesil (Prunus mume Siebold & Zucc.), a potential source of free radical
      scavengers and inhibitor of pro-inflammatory mediators, is used in traditional
      Korean medical preparations as a remedy for skin disorders as have probiotics.
      The action of a probiotic fermented Maesil preparation on the development of
      atopic dermatitis (AD)-like skin lesions was determined in a NC/Nga mouse model
      as an initial step towards the development of a therapeutic feed supplement for
      use in dogs. Continuous ingestion of the experimental feed markedly inhibited the
      development of the AD-like skin lesions, as evidenced by a marked decrease in
      skin signs and reduced inflammation within the skin lesions. Efficacy was
      confirmed by significant decreases in eosinophil ratio and serum IgE
      concentration, and a reduction in the number of Staphylococcus aureus recovered
      from the ear. Relative mRNA expression levels of IL-4, interferon-gamma and
      tumour necrosis factor-alpha in the spleens of the experimental animals were also
      decreased and there was an increased serum concentration of IL-10 with a
      concurrent decreased IL-4 concentration in comparison to a control group. Taken
      together, the results indicate that some component(s) of fermented Maesil have
      the ability to suppress the development of AD-like skin lesions, possibly by
      stimulation of IL-10. Beneficial effects of fermented Maesil may thus be expected
      in dogs with AD, although this and the nature of the active pathway remain to be
      explored.

PMID- 20141606
TI  - Canine cutaneous epitheliotropic T-cell lymphoma: a review of 30 cases.
AB  - This retrospective study reviewed the clinical, histological and
      immunohistochemical features of 30 European cases of canine cutaneous
      epitheliotropic T-cell lymphoma (CETL). The clinical presentation was highly
      variable and was not associated with the disease subtype. Diffuse erythema
      (86.6%) with scaling (60%) and focal hypopigmentation (50%) were the most common
      lesions. The skin was uniformly involved but muco-cutaneous junctions or mucosae
      were affected in 50% of cases. The median age at diagnosis was 10 years (SD 2.79,
      range 4-15) and the median time between onset and final diagnosis was 5 months
      (SD 3.79, range 0-12). Five cases occurred in Bichon Frises. There was no
      evidence of a previous history of chronic dermatitis in any cases.
      Histologically, the follicular epithelium was affected in 86.7% of cases. One
      case with mainly follicular disease was considered folliculotropic mycosis
      fungoides (MF), but no follicular mucinosis was observed. Epidermal Pautrier's
      microabscesses were uncommon (23.3%). Sweat glands were infiltrated in 70% of
      cases. Immunohistochemistry confirmed T-cell neoplasia in all cases. B cells
      infiltrated as individual cells or formed linear bands or ectopic follicles at
      the base of the neoplasm. Ki67 labelling revealed a range of proliferation
      indices but did not correlate with severity. A final diagnosis of classical MF
      was made in 40% of the dogs, MF d'emble in 36.7%, generalized Pagetoid
      reticulosis in 20% and localized Pagetoid reticulosis in one case (Woringer
      Kolopp Pagetoid reticulosis). The median survival time after diagnosis was 6
      months and this did not change appreciably with therapy (lomustine or
      prednisolone).

PMID- 20141608
TI  - Endogenous n-3 fatty acids protect ovariectomy induced bone loss by attenuating
      osteoclastogenesis.
AB  - Beneficial effects of n-3 fatty acids (FA) on bone mineral density (BMD) have
      been reported in mice, rats and human beings, but the precise mechanisms involved
      have not been described. This study used the Fat-1 mouse, a transgenic model that
      synthesizes n-3 FA from n-6 FA to directly determine if outcome of bone health
      were correlated with n-3 FA. Ovariectomized (Ovx) and sham operated wild-type
      (WT) and Fat-1 mice were fed an AIN-93M diet containing 10% corn oil for 24
      weeks. BMD was analysed by dual energy x-ray absorptiometry. Fat-1 Ovx mice
      exhibited significantly lower level of osteotropic factors like receptor
      activator of NF-kappaB ligand and tartrate-resistant acid phosphatase (TRAP)5b in
      serum and higher BMD in distal femoral metaphysis, proximal tibial metaphysis,
      femoral diaphysis and lumbar vertebra as compared to WT Ovx mice. LPS-stimulated
      bone marrow (BM) cells from Fat-1 Ovx mice produced significantly lower level of
      pro-inflammatory cytokines like tumour necrosis factor-alpha, interleukin (IL)-1
      beta, IL-6 and higher level of anti-inflammatory cytokines like IL-10, IFN-gamma
      and higher level of nitric oxide as compared to BM cells from WT Ovx mice. LPS
      stimulated COX-II activity as well as NF-kappaB activation in BM cells from Fat-1
      Ovx mice was significantly less as compared to BM cells from WT Ovx mice.
      Furthermore, Fat-1 BM cells generated significantly less number of TRAP
      osteoclast-like cells as compared to WT BM cells. In conclusion, we offer further
      insight into the mechanisms involved in preventing the BMD loss in Ovx mice by n
      3 FA using a Fat-1 transgenic mouse model.

PMID- 20141609
TI  - Calcium and ER stress mediate hepatic apoptosis after burn injury.
AB  - A hallmark of the disease state following severe burn injury is decreased liver
      function, which results in gross metabolic derangements that compromise patient
      survival. The underlying mechanisms leading to hepatocyte dysfunction after burn
      are essentially unknown. The aim of the present study was to determine the
      underlying mechanisms leading to hepatocyte dysfunction and apoptosis after burn.
      Rats were randomized to either control (no burn) or burn (60% total body surface
      area burn) and sacrificed at various time-points. Liver was either perfused to
      isolate primary rat hepatocytes, which were used for in vitro calcium imaging, or
      liver was harvested and processed for immunohistology, transmission electron
      microscopy, mitochondrial isolation, mass spectroscopy or Western blotting to
      determine the hepatic response to burn injury in vivo. We found that thermal
      injury leads to severely depleted endoplasmic reticulum (ER) calcium stores and
      consequent elevated cytosolic calcium concentrations in primary hepatocytes in
      vitro. Burn-induced ER calcium depletion caused depressed hepatocyte
      responsiveness to signalling molecules that regulate hepatic homeostasis, such as
      vasopressin and the purinergic agonist ATP. In vivo, thermal injury resulted in
      activation of the ER stress response and major alterations in mitochondrial
      structure and function - effects which may be mediated by increased calcium
      release by inositol 1,4,5-trisphosphate receptors. Our results reveal that
      thermal injury leads to dramatic hepatic disturbances in calcium homeostasis and
      resultant ER stress leading to mitochondrial abnormalities contributing to
      hepatic dysfunction and apoptosis after burn injury.

PMID- 20141611
TI  - A novel histone deacetylase inhibitor prevents IL-1beta induced metabolic
      dysfunction in pancreatic beta-cells.
AB  - The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has recently been
      shown to inhibit deleterious effects of cytokines on beta-cells, but it is unable
      to protect beta-cells from death due to its own cytotoxicity. Herein, we
      investigated novel HDAC inhibitors for their cytoprotective effects against IL
      1beta-induced damage to isolated beta-cells. We report that three novel compounds
      (THS-73-44, THS-72-5 and THS-78-5) significantly inhibited HDAC activity and
      increased the acetylation of histone H4 in isolated beta-cells. Further, these
      compounds exerted no toxic effects on metabolic cell viability in these cells.
      However, among the three compounds tested, only THS-78-5 protected against IL
      1beta-mediated loss in beta-cell viability. THS-78-5 was also able to attenuate
      IL-1beta-induced inducible nitric oxide synthase expression and subsequent NO
      release. Our data also indicate that the cytoprotective properties of THS-78-5
      against IL-1beta-mediated effects may, in part, be due to inhibition of IL-1beta
      induced transactivation of nuclear factor kappaB (NF-kappaB) in these cells.
      Together, we provide evidence for a novel HDAC inhibitor with a significant
      potential to prevent IL-1beta-mediated effects on isolated beta-cells. Potential
      implications of these findings in the development of novel therapeutics to
      prevent deleterious effects of cytokines and the onset of autoimmune diabetes are
      discussed.

PMID- 20141610
TI  - TNF-alpha induces TGF-beta1 expression in lung fibroblasts at the transcriptional
      level via AP-1 activation.
AB  - Tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(1)
      (TGF-beta(1)) are peptides with multiple biological activities that influence
      neoplastic, immunologic and fibroproliferative diseases. There are clear
      interrelationships and overlap between the actions of TNF-alpha and TGF-beta(1)
      in lung fibrosis; therefore, we postulated that TNF-alpha may play a significant
      role in regulating TGF-beta(1) expression in lungs. We recently reported that TNF
      alpha activates the extracellular regulated kinase (ERK)-specific pathway in
      fibroblasts resulting in stabilization of TGF-beta(1) mRNA and increased
      expression of TGF-beta(1). In the current study, we further investigated the
      molecular mechanisms involved in TNF-alpha regulation of TGF-beta(1) expression.
      Nuclear run-on assays showed that treatment of Swiss 3T3 fibroblasts with TNF
      alpha increased transcription of the TGF-beta(1) gene in an ERK independent
      manner. Pre-treatment with the activator protein-1 (AP-1) inhibitor curcumin
      attenuated TNF-alpha induced transcription of the TGF-beta(1) gene. TNF-alpha
      induced increased levels of c-Jun and C-Fos in the nucleus accompanied by
      phosphorylation of c-Jun. In electrophoretic mobility shift assays, AP-1 binding
      to an AP-1 binding site found within the TGF-beta(1) promoter was increased in
      nuclear extracts from Swiss 3T3 fibroblasts treated with TNF-alpha. Together,
      these results suggest that TNF-alpha induces expression and DNA binding of AP-1
      resulting in increased transcription of the TGF-beta(1) gene. It is essential to
      know which transcription pathways are activated because of the wide distribution
      of TNF-alpha and TGF-beta(1), the general lack of effective treatments for
      fibroproliferative disease and the possibility that targeting the correct
      transcription factors could be palliative.

PMID- 20141612
TI  - The ubiquitin specific protease 4 (USP4) is a new player in the Wnt signalling
      pathway.
AB  - The canonical Wnt signalling pathway is essential for cell fate determination
      during embryonic development and for the maintenance of adult tissue homeostasis.
      Deregulation of Wnt signalling leads to developmental defects and is associated
      with various types of cancer. Here we have used an RNA interference (RNAi)
      library specifically targeting human deubiquitinating enzymes (DUBs) to screen
      for new regulators of the canonical Wnt signalling pathway. We found that
      suppression of the ubiquitin specific protease 4 (USP4) activates beta-catenin
      dependent transcription. We also show that USP4 is a DUB with dual hydrolysing
      activity for K(48)- and K(63)-conjugated polyubiquitin chains and interacts with
      two known Wnt signalling components: the Nemo like kinase (Nlk) and the
      transcription factor (T-cell factor 4 [TCF4]). Overexpression of a catalytically
      active Nlk promotes nuclear accumulation of USP4 whereas a subpopulation of TCF4
      is a substrate of USP4-dependent deubiquitination. Thus, modulation of USP4
      expression may provide a new means to interfere with canonical Wnt signalling in
      a variety of physiological and pathological conditions.

PMID- 20141613
TI  - Stimulation of protein kinase C-alpha suppresses colon cancer cell proliferation
      by down-regulation of beta-catenin.
AB  - We reported previously that protein kinase C-alpha (PKC-alpha) negatively
      regulates Wnt/beta-catenin signalling pathway. The current study explores the
      role of PKC-alpha in the regulation of proliferation of colon cancer cells, which
      contain aberrant up-regulation of intracellular beta-catenin. In colon tissue and
      cells, an inverse correlation was observed between the expression levels of PKC
      alpha and intracellular beta-catenin. Activation of PKC-alpha inhibited beta
      catenin response transcription by down-regulation of intracellular beta-catenin
      and induced phosphorylation of the N-terminal serine and threonine residues
      (Ser33/Ser37/Thr41) of beta-catenin, marking it for proteasomal degradation, in
      colon cancer cells. Pharmacological inhibition or depletion of PKC-alpha
      abrogated PKC-alpha-mediated beta-catenin down-regulation and phosphorylation in
      colon cancer cells. Notably, the Ser45 residue of beta-catenin was essential for
      PKC-alpha-induced beta-catenin down-regulation in colon cancer cells. Moreover,
      PKC-alpha activation repressed the expression of cyclin D1 and c-myc, which are
      known beta-catenin target genes, and thus inhibited the growth of colon cancer
      cells. These findings suggest that PKC-alpha negatively regulates colon cancer
      cell proliferation viabeta-catenin phosphorylation/down-regulation and may
      facilitate the development of new strategies to treatment of colon cancer.

PMID- 20141614
TI  - Calcium sensing receptor-dependent and receptor-independent activation of
      osteoblast replication and survival by strontium ranelate.
AB  - Age-related osteopenia is characterized by a negative balance between bone
      resorption and formation. The anti-osteoporotic drug strontium ranelate was found
      to reduce bone resorption and to promote bone formation. Here, we investigated
      the implication of the calcium-sensing receptor (CaSR) in the response to
      strontium ranelate using osteoblasts from CaSR knockout [CaSR(-/-)] and wild-type
      [CaSR(+/+)] mice. We showed that calcium and strontium ranelates increased cell
      replication in [CaSR(-/-)] and [CaSR(+/+)] osteoblasts. Strontium ranelate
      rapidly increased ERK1/2 phosphorylation in [CaSR(+/+)] but not in [CaSR(-/-)]
      osteoblasts, indicating that strontium ranelate can act independent of the
      CaSR/ERK1/2 cascade to promote osteoblast replication. We also showed that
      strontium ranelate prevented cell apoptosis induced by serum deprivation or the
      pro-inflammatory cytokines IL-1beta and TNF-alpha in [CaSR(-/-)] and [CaSR(+/+)]
      osteoblasts, indicating that CaSR is not the only receptor involved in the
      protective effect of strontium ranelate on osteoblast apoptosis. Strontium
      ranelate activated the Akt pro-survival pathway in [CaSR(-/-)] and [CaSR(+/+)]
      osteoblasts, and pharmacological inhibition of Akt abrogated the anti-apoptotic
      effect of strontium ranelate. Furthermore, both the proliferative and anti
      apoptotic effects of strontium ranelate in [CaSR(-/-)] and [CaSR(+/+)]
      osteoblasts were abrogated by selective inhibition of COX-2. The results provide
      genetic and biochemical evidence that the effects of strontium ranelate on
      osteoblast replication and survival involve ERK1/2 and Akt signalling and PGE2
      production, independent of CaSR expression. The finding that CaSR-dependent and
      CaSR-independent pathways mediate the beneficial effects of strontium ranelate on
      osteoblasts, provides novel insight into the mechanism of action of this anti
      osteoporotic agent on osteoblastogenesis.

PMID- 20141615
TI  - Oestrogen modulates human macrophage apoptosis via differential signalling
      through oestrogen receptor-alpha and beta.
AB  - Human macrophages express oestrogen receptors and are therefore competent to
      respond to the hormone present in their microenvironment, which is implicated in
      sexual dimorphism observed in several immune and autoimmune phenomena. An earlier
      study from this laboratory demonstrated 17beta-oestradiol (E2) induced apoptosis
      in macrophages derived from human peripheral blood monocytes and THP-1 acute
      monocytic leukaemia cell line when Bcl-2 was down-regulated; however, the
      involvement of E2 receptor subtypes in the modulation of death pathways in these
      cells remain unknown. Using macrophages derived from THP-1 human acute monocytic
      leukaemia cells as a model, we demonstrate that plasma membrane associated
      oestrogen receptor (ER) -alpha participate in E2 induced Bcl-2 increase, through
      activation of the mitogen activated protein kinase (MAPK) pathway whereas
      cytosolic ER-beta transmits signals for the pro-apoptotic event of Bax
      translocation. The mechanistic basis of Bax translocation comprised of ER-beta
      mediated increase in intracellular pH, facilitated by activation of the Na(+)
      H(+) exchanger. Intracellular alkalinization accompanied by concomitant Bcl-2
      increase and Bax migration does not cause cellular apoptosis; however, siRNA
      mediated down-regulation of ER-alpha during E2 exposure leads to inhibition of
      Bcl-2 increase and consequently apoptosis due to the unopposed action of
      mitochondrial Bax. In summary, this study underscores the importance of
      integrative signalling modality from multiple oestrogen receptor pools in
      modulating oestrogen effects on human monocyte-derived macrophage apoptotic
      signalling pathway, which opens new vistas to explore the use of selective
      oestrogen receptor modulators in apoptosis-based therapies.

PMID- 20141616
TI  - Differential regulation of connective tissue growth factor in renal cells by
      histone deacetylase inhibitors.
AB  - Regulation of the profibrotic and angiogenesis modulating cytokine connective
      tissue growth factor (CTGF) occurs primarily at the transcriptional level.
      Therefore, we hypothesized that histone deacetylating enzymes (HDAC), which
      modulate the accessibility of transcriptionally active promoter regions, might
      play a role in the regulation of CTGF gene expression. We analyzed microvascular
      endothelial cells, which showed immunoreactivity for acetylated histone in kidney
      sections, and compared them with renal tubular epithelial cells. Treatment of
      cultured endothelial cells with different HDAC inhibitors up-regulated CTGF mRNA
      and protein. Pre-treatment with HDAC inhibitors facilitated induction of CTGF by
      transforming growth factor-beta (TGF-beta) or lysophosphatidic acid.
      Transcription factors of the FoxO family were involved in the up-regulation of
      CTGF as shown at protein level and by reporter gene analyses. In tubular
      epithelial cells, up-regulation of CTGF was only observed when these cells were
      cultured as subconfluent cells. Dense cells, which are more likely to resemble
      tubular cells in vivo, showed no up-regulation upon treatment with HDAC
      inhibitors and were protected against CTGF induction by TGF-beta. Taken together,
      our data indicate that the effect of HDAC inhibitors on CTGF expression is
      largely cell dependent in non-tumour cells. Different cell type-specific
      transcription factors seem to determine whether CTGF expression is reduced or
      increased in cells exposed to HDAC inhibitors.

PMID- 20141617
TI  - Characterization of the S-denitrosylating activity of bilirubin.
AB  - Bilirubin-IX-alpha (BR) is an endogenous molecule with a strong antioxidant
      feature due to its ability to scavenge free radicals. In this paper, we
      demonstrated that BR, at concentrations close to those found within the cell (0.1
      2.5 microM), acted as a denitrosylating agent and increased the release of nitric
      oxide from S-nitrosoglutathione (GSNO) and S-nitrosocysteine (SNOC) (2.5 microM).
      The complexation of BR with saturating concentrations of human serum albumin
      (HSA, 2.5 microM) did not further increase nitric oxide release from GSNO and
      SNOC. At concentrations similar to those reached in plasma (5-20 microM), BR
      denitrosylated S-nitroso-HSA (2.5 microM), the main circulating S-nitrosothiol,
      and this effect was potentiated by the complexation of BR with saturating HSA (20
      microM). Furthermore, the product(s) of the reaction between nitric oxide and BR
      were identified. Ultraviolet and mass spectrometry analysis revealed that nitric
      oxide binds to BR forming a N-nitroso derivative (BR-nitric oxide) with
      extinction coefficients of 1.393 mM(-1)cm(-1) and 2.254 mM(-1)cm(-1) in methanol
      and NaOH, respectively. The formation of BR-nitric oxide did not occur only in a
      reconstituted system, but was confirmed in rat fibroblasts exposed to pro-oxidant
      stimuli. These results provided novel insights on the antioxidant characteristic
      of BR through its interaction with nitric oxide, a gaseous neurotransmitter with
      a well-known dual effect, namely neuroprotective under physiological conditions
      or neurotoxic if produced in excess, and proposed BR-nitric oxide as a new
      biomarker of oxidative/nitrosative stress.

PMID- 20141619
TI  - Mesenchymal stem cells induce a weak immune response in the rat striatum after
      allo or xenotransplantation.
AB  - Mesenchymal stem cells (MSCs) have attracted attention for their potential use in
      regenerative medicine such as brain transplantation. As MSCs are considered to be
      hypoimmunogenic, transplanted MSCs should not trigger a strong host inflammatory
      response. To verify this hypothesis, we studied the brain immune response after
      transplantation of human or rat MSCs into the rat striatum and MSC fate at days
      5, 14, 21 and 63 after transplantation. Flow cytometry analysis indicated that
      both MSCs express CD90 and human leucocyte antigen (MHC) class I, but no MHC
      class II molecules. They do not express CD45 or CD34 antigens. However, MSC
      phenotype varies with passage number. Human MSCs have mRNAs for interleukin (IL)
      6, IL-8, IL-12, tumour necrosis factor (TNF)-alpha and TGF-beta(1), whereas rat
      MSCs express IL-6-, IL-10-, IL-12- and TGF-beta(1)-mRNAs. The quantification
      shows higher levels of mRNAs for the anti-inflammatory molecules IL-6 and TGF
      beta(1) than for pro-inflammatory cytokines IL-8 and IL-12; ELISA analysis showed
      no IL-12 whereas TGF-beta(1) and IL-6 were detected. Transplant size did not
      significantly vary between 14 and 63 days after transplantation, indicating an
      absence of immune rejection of the grafts. Very few mast cells and moderate
      macrophage and microglial infiltrations, observed at day 5 remained stable until
      day 63 after transplantation in both rat and human MSC grafts. The observations
      of very few dendritic cells, T alphabeta-cells, and no T gammadelta-lymphocytes,
      all three being associated with Tp rejection in the brain, support the contention
      that MSCs are hypoimmunogenic. Our results suggest that MSCs are of great
      interest in regenerative medicine in a (xeno)transplantation setting.

PMID- 20141618
TI  - Vulnerability of hippocampal GABA-ergic interneurons to kainate-induced
      excitotoxic injury during old age.
AB  - Hippocampal inhibitory interneurons expressing glutamate decarboxylase-67 (GAD
      67) considerably decline in number during old age. Studies in young adult animals
      further suggest that hippocampal GAD-67+ interneuron population is highly
      vulnerable to excitotoxic injury. However, the relative susceptibility of
      residual GAD-67+ interneurons in the aged hippocampus to excitotoxic injury is
      unknown. To elucidate this, using both adult and aged F344 rats, we performed
      stereological counting of GAD-67+ interneurons in different layers of the dentate
      gyrus and CA1 & CA3 sub-fields, at 3 months post-excitotoxic hippocampal injury
      inflicted through an intracerebroventricular administration of kainic acid (KA).
      Substantial reductions of GAD-67+ interneurons were found in all hippocampal
      layers and sub-fields after KA-induced injury in adult animals. Contrastingly,
      there was no significant change in GAD-67+ interneuron population in any of the
      hippocampal layers and sub-fields following similar injury in aged animals.
      Furthermore, the stability of GAD-67+ interneurons in aged rats after KA was not
      attributable to milder injury, as the overall extent of KA-induced hippocampal
      principal neuron loss was comparable between adult and aged rats. Interestingly,
      because of the age-related disparity in vulnerability of interneurons to injury,
      the surviving GAD-67+ interneuron population in the injured aged hippocampus
      remained comparable to that observed in the injured adult hippocampus despite
      enduring significant reductions in interneuron number with aging. Thus, unlike in
      the adult hippocampus, an excitotoxic injury to the aged hippocampus does not
      result in significantly decreased numbers of GAD-67+ interneurons. Persistence of
      GAD-67+ interneuron population in the injured aged hippocampus likely reflects an
      age-related change in the response of GAD-67+ interneurons to excitotoxic
      hippocampal injury. These results have implications towards understanding
      mechanisms underlying the evolution of initial precipitating injury into temporal
      lobe epilepsy in the elderly population.

PMID- 20141620
TI  - Anti-inflammatory effects of low molecular weight heparin derivative in a rat
      model of carrageenan-induced pleurisy.
AB  - Low molecular weight heparin derivatives are characterized by low anti-coagulant
      activity and marked anti-inflammatory effects that allow for these molecules to
      be viewed as a new class of non-steroidal anti-inflammatory drugs (NSAIDs). We
      show here that K5NOSepiLMW, an O-sulphated heparin-like semi-synthetic polymer of
      the D-glucuronic acid-N-acetyleparoson disaccharide unit with low molecular
      weight, has marked anti-inflammatory effects in a rat model of acute
      inflammation, the carrageenan-induced pleurisy, commonly used to test NSAID
      efficacy. A 30-min. pre-treatment with K5NOSepiLMW (0.1, 0.5 and 1 mg/kg b.wt.,
      given intrapleurally) attenuated the recruitment of leucocytes in the lung tissue
      and the pleural exudate, inhibited the induction of inducible nitric oxide
      synthase and cyclooxygenase-2 (COX-2), thereby abating the generation of nitric
      oxide and pro-inflammatory prostaglandins such as PgE(2) and PGF(1alpha), reduced
      the inflammation-induced nitroxidative lung tissue injury, as shown by tissue
      thiobarbituric acid-reactive substances and nitrotyrosine, and blunted the local
      generation of cytokines such as interleukin-1beta and tumour necrosis factor
      alpha. All these parameters were markedly increased by intrapleural carrageenan
      in the absence of any pre-treatment. The anti-inflammatory action of K5NOSepiLMW
      is specific, as judged by the lack of therapeutic effects of B4/110, a
      biologically inactive cognate polysaccharide, given in the place of the authentic
      molecule. Moreover, K5NOSepiLMW showed similar effects as celecoxib (1 mg/kg
      b.wt), a COX-2 inhibitor and well-known NSAID. This study provides further
      insight into the mechanisms underlying the beneficial effects of heparin
      derivatives in inflammation and identifies K5NOSepiLMW as a novel, promising anti
      inflammatory drug.

PMID- 20141622
TI  - The origin of populations of Arabidopsis thaliana in China, based on the
      chloroplast DNA sequences.
AB  - BACKGROUND: In the studies incorporating worldwide sampling of A. thaliana
      populations, the samples from East Asia, especially from China, were very
      scattered; and the studies focused on global patterns of cpDNA genetic variation
      among accessions of A. thaliana are very few. In this study, chloroplast DNA
      sequence variability was used to infer phylogenetic relationships among
      Arabidopsis thaliana accessions from around the world, with the emphasis on
      samples from China. RESULTS: A data set comprising 77 accessions of A. thaliana,
      including 19 field-collected Chinese accessions together with three related
      species (A. arenosa, A. suecica, and Olimarabidopsis cabulica) as the out-group,
      was compiled. The analysis of the nucleotide sequences showed that the 77
      accessions of A. thaliana were partitioned into two major differentiated
      haplotype classes (MDHCs). The estimated divergence time of the two MDHCs was
      about 0.39 mya. Forty-nine haplotypes were detected among the 77 accessions,
      which exhibited nucleotide diversity (pi) of 0.00169. The Chinese populations
      along the Yangtze River were characterized by five haplotypes, and the two
      accessions collected from the middle range of the Altai Mountains in China shared
      six specific variable sites. CONCLUSIONS: The dimorphism in the chloroplast DNA
      could be due to founder effects during late Pleistocene glaciations and
      interglacial periods, although introgression cannot be ruled out. The Chinese
      populations along the Yangtze River may have dispersed eastwards to their present
      day locations from the Himalayas. These populations originated from a common
      ancestor, and a rapid demographic expansion began approximately 90,000 years ago.
      Two accessions collected from the middle range of the Altai Mountains in China
      may have survived in a local refugium during late Pleistocene glaciations. The
      natural populations from China with specific genetic characteristics enriched the
      gene pools of global A. thaliana collections.

PMID- 20141623
TI  - Development of a EST dataset and characterization of EST-SSRs in a traditional
      Chinese medicinal plant, Epimedium sagittatum (Sieb. Et Zucc.) Maxim.
AB  - BACKGROUND: Epimedium sagittatum (Sieb. Et Zucc.) Maxim, a traditional Chinese
      medicinal plant species, has been used extensively as genuine medicinal
      materials. Certain Epimedium species are endangered due to commercial
      overexploition, while sustainable application studies, conservation genetics,
      systematics, and marker-assisted selection (MAS) of Epimedium is less-studied due
      to the lack of molecular markers. Here, we report a set of expressed sequence
      tags (ESTs) and simple sequence repeats (SSRs) identified in these ESTs for E.
      sagittatum. RESULTS: cDNAs of E. sagittatum are sequenced using 454 GS-FLX
      pyrosequencing technology. The raw reads are cleaned and assembled into a total
      of 76,459 consensus sequences comprising of 17,231 contigs and 59,228 singlets.
      About 38.5% (29,466) of the consensus sequences significantly match to the non
      redundant protein database (E-value < 1e-10), 22,295 of which are further
      annotated using Gene Ontology (GO) terms. A total of 2,810 EST-SSRs is identified
      from the Epimedium EST dataset. Trinucleotide SSR is the dominant repeat type
      (55.2%) followed by dinucleotide (30.4%), tetranuleotide (7.3%), hexanucleotide
      (4.9%), and pentanucleotide (2.2%) SSR. The dominant repeat motif is AAG/CTT
      (23.6%) followed by AG/CT (19.3%), ACC/GGT (11.1%), AT/AT (7.5%), and AAC/GTT
      (5.9%). Thirty-two SSR-ESTs are randomly selected and primer pairs are
      synthesized for testing the transferability across 52 Epimedium species. Eighteen
      primer pairs (85.7%) could be successfully transferred to Epimedium species and
      sixteen of those show high genetic diversity with 0.35 of observed heterozygosity
      (Ho) and 0.65 of expected heterozygosity (He) and high number of alleles per
      locus (11.9). CONCLUSION: A large EST dataset with a total of 76,459 consensus
      sequences is generated, aiming to provide sequence information for deciphering
      secondary metabolism, especially for flavonoid pathway in Epimedium. A total of
      2,810 EST-SSRs is identified from EST dataset and approximately 1580 EST-SSR
      markers are transferable. E. sagittatum EST-SSR transferability to the major
      Epimedium germplasm is up to 85.7%. Therefore, this EST dataset and EST-SSRs will
      be a powerful resource for further studies such as taxonomy, molecular breeding,
      genetics, genomics, and secondary metabolism in Epimedium species.

PMID- 20141624
TI  - Regional differences in recombination hotspots between two chicken populations.
AB  - BACKGROUND: Although several genetic linkage maps of the chicken genome have been
      published, the resolution of these maps is limited and does not allow the precise
      identification of recombination hotspots. The availability of more than 3.2
      million SNPs in the chicken genome and the recent advances in high throughput
      genotyping techniques enabled us to increase marker density for the construction
      of a high-resolution linkage map of the chicken genome. This high-resolution
      linkage map allowed us to study recombination hotspots across the genome between
      two chicken populations: a purebred broiler line and a broiler x broiler cross.
      In total, 1,619 animals from the two different broiler populations were genotyped
      with 17,790 SNPs. RESULTS: The resulting linkage map comprises 13,340 SNPs.
      Although 360 polymorphic SNPs that had not been assigned to a known chromosome on
      chicken genome build WASHUC2 were included in this study, no new linkage groups
      were found. The resulting linkage map is composed of 31 linkage groups, with a
      total length of 3,054 cM for the sex-average map of the combined population. The
      sex-average linkage map of the purebred broiler line is 686 cM smaller than the
      linkage map of the broiler x broiler cross. CONCLUSIONS: In this study, we
      present a linkage map of the chicken genome at a substantially higher resolution
      than previously published linkage maps. Regional differences in recombination
      hotspots between the two mapping populations were observed in several chromosomes
      near the telomere of the p arm; the sex-specific analysis revealed that these
      regional differences were mainly caused by female-specific recombination hotspots
      in the broiler x broiler cross.

PMID- 20141625
TI  - Food seeking in spite of harmful consequences is under prefrontal cortical
      noradrenergic control.
AB  - BACKGROUND: Eating disorders are multifactorial psychiatric disorders. Chronic
      stressful experiences and caloric restriction are the most powerful triggers of
      eating disorders in human and animals. Although compulsive behavior is considered
      to characterize pathological excessive food intake, to our knowledge, no evidence
      has been reported of continued food seeking/intake despite its possible harmful
      consequences, an index of compulsive behavior. Brain monoamine transmission is
      considered to have a key role in vulnerability to eating disorders, and
      norepinephrine in medial prefrontal cortex has been shown to be critical for food
      related motivated behavior.Here, using a new paradigm of conditioned suppression,
      we investigated whether the ability of a foot-shock-paired conditioned stimulus
      to suppress chocolate-seeking behavior was reversed by previous exposure to a
      food restriction experience, thus modeling food seeking in spite of harmful
      consequences in mice. Moreover, we assessed the effects of selective
      norepinephrine inactivation in medial prefrontal cortex on conditioned
      suppression test in stressed and caloric restricted mice. RESULTS: While Control
      (non food deprived) animals showed a profound conditioned suppression of
      chocolate seeking during presentation of conditioned stimulus, previously food
      restricted animals showed food seeking/intake despite its possible harmful
      consequences. Moreover, food seeking in spite of harmful consequences was
      prevented by selective norepinephrine inactivation, thus showing that prefrontal
      cortical norepinephrine is critical also for maladaptive food-related behavior.
      CONCLUSIONS: These findings indicate that adaptive food seeking/intake can be
      transformed into maladaptive behaviors and point to "top-down" influence on
      eating disturbances and to new targets for therapy of aberrant eating behaviors.

PMID- 20141626
TI  - Control of pyrethroid and DDT-resistant Anopheles gambiae by application of
      indoor residual spraying or mosquito nets treated with a long-lasting
      organophosphate insecticide, chlorpyrifos-methyl.
AB  - BACKGROUND: Scaling up of long-lasting insecticidal nets (LLINs) and indoor
      residual spraying (IRS) with support from the Global Fund and President's Malaria
      Initiative is providing increased opportunities for malaria control in Africa.
      The most cost-effective and longest-lasting residual insecticide DDT is also the
      most environmentally persistent. Alternative residual insecticides exist, but are
      too short-lived or too expensive to sustain. Dow Agrosciences have developed a
      microencapsulated formulation (CS) of the organophosphate chlorpyrifos methyl as
      a cost-effective, long-lasting alternative to DDT. METHODS: Chlorpyrifos methyl
      CS was tested as an IRS or ITN treatment in experimental huts in an area of Benin
      where Anopheles gambiae and Culex quinquefasiactus are resistant to pyrethroids,
      but susceptible to organophosphates. Efficacy and residual activity was compared
      to that of DDT and the pyrethroid lambdacyalothrin. RESULTS: IRS with
      chlorpyrifos methyl killed 95% of An. gambiae that entered the hut as compared to
      31% with lambdacyhalothrin and 50% with DDT. Control of Cx. quinquefasciatus
      showed a similar trend; although the level of mortality with chlorpyrifos methyl
      was lower (66%) it was still much higher than for DDT (14%) or pyrethroid (15%)
      treatments. Nets impregnated with lambdacyhalothrin were compromised by
      resistance, killing only 30% of An. gambiae and 8% of Cx. quinquefasciatus. Nets
      impregnated with chlorpyrifos methyl killed more (45% of An gambiae and 15% of
      Cx. quinquefasciatus), but its activity on netting was of short duration. Contact
      bioassays on the sprayed cement-sand walls over the nine months of monitoring
      showed no loss of activity of chlorpyrifos methyl, whereas lambdacyhalothrin and
      DDT lost activity within a few months of spraying. CONCLUSION: As an IRS
      treatment against pyrethroid resistant mosquitoes chlorpyrifos methyl CS
      outperformed DDT and lambdacyhalothrin. In IRS campaigns, chlorpyrifos methyl CS
      should show higher, more-sustained levels of malaria transmission control than
      conventional formulations of DDT or pyrethroids. The remarkable residual activity
      indicates that cost-effective alternatives to DDT are feasible through modern
      formulation technology.

PMID- 20141627
TI  - BDNF Val66Met polymorphism and protein levels in amniotic fluid.
AB  - BACKGROUND: Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which
      plays survival- and growth-promoting activity in neuronal cells and it is
      involved in cellular plasticity mechanisms as it controls activity dependent
      synaptic transmission. A functional polymorphism (Val66Met) in the pro-region of
      BDNF, which affects the intracellular trafficking of proBDNF has been associated
      with memory and cognitive deficits as well as to an increased susceptibility for
      several psychiatric disorders especially those with a neurodevelopmental origin.
      To date, no study has evaluated the influence of the Val66Met polymorphism on
      BDNF levels in a peripheral system that may reflect fetal neurodevelopment.
      Therefore we investigated in amniotic fluids (AF) obtained from 139 healthy women
      during 15-17 week of pregnancy, BDNF protein levels in correlation with the
      Val66Met polymorphism. RESULTS: Interestingly we found a significant BDNF protein
      levels reduction in 55 Met carriers (Val/Met and Met/Met) (p = 0.002) as compared
      to 84 non carriers (Val/Val), and no effect of fetus gender, maternal age or
      gestation week on BDNF levels has been observed. CONCLUSION: These results,
      although explorative, indicate that during fetal life the Val66Met genotype might
      influences BDNF protein levels in AF supporting the involvement of this
      polymorphism in behavioral and functional brain individual differences in the
      adulthood.

PMID- 20141628
TI  - Local leptin production in osteoarthritis subchondral osteoblasts may be
      responsible for their abnormal phenotypic expression.
AB  - INTRODUCTION: Leptin is a peptide hormone with a role in bone metabolism and
      rheumatic diseases. The subchondral bone tissue plays a prominent role in the
      pathophysiology of osteoarthritis (OA), related to abnormal osteoblast (Ob)
      differentiation. Although leptin promotes the differentiation of Ob under normal
      conditions, a role for leptin in OA Ob has not been demonstrated. Here we
      determined if endogenous leptin produced by OA Ob could be responsible for the
      expression of the abnormal phenotypic biomarkers observed in OA Ob. METHODS: We
      prepared primary normal and OA Ob from subchondral bone of tibial plateaus
      removed for knee surgery of OA patients or at autopsy. We determined the
      production of leptin and of the long, biologically active, leptin receptors (OB
      Rb) using reverse transcriptase-polymerase chain reaction, ELISA and Western blot
      analysis. We determined the effect of leptin on cell proliferation by BrdU
      incorporation and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assays, and we determined by Western blot analysis phospho 42/44 MAPK
      (p42/44 Erk1/2) and phospho p38 levels. We then determined the effect of the
      addition of exogenous leptin, leptin receptor antagonists, inhibitors of leptin
      signaling or siRNA techniques on the phenotypic features of OA Ob. Phenotypic
      features of Ob were determined by measuring alkaline phosphatase activity (ALP),
      osteocalcin release (OC), collagen type 1 production (CICP) and of Transforming
      Growth Factor-beta1 (TGF-beta1). RESULTS: Leptin expression was increased
      approximately five-fold and protein levels approximately two-fold in OA Ob
      compared to normal. Leptin stimulated its own expression and the expression of OB
      Rb in OA Ob. Leptin dose-dependently stimulated cell proliferation of OA Ob and
      also increased phosphorylated p42/44 Erk1/2 and p38 levels. Inactivating
      antibodies against leptin reduced ALP, OC, CICP and TGF-beta1 levels in OA Ob.
      Tyrphostin (AG490) and piceatannol (Pce), inhibitors of leptin signaling,
      reproduced this effect. Inhibition of endogenous leptin levels using siRNA for
      leptin or inhibiting leptin signaling using siRNA for OB-Rb expression both
      reduced ALP and OC about 60%. Exogenous leptin addition stimulated ALP, yet this
      failed to further increase OC or CICP. CONCLUSIONS: These results suggest that
      abnormal production of leptin by OA Ob could be responsible, in part, for the
      elevated levels of ALP, OC, collagen type 1 and TGF-beta1 observed in these cells
      compared to normal. Leptin also stimulated cell proliferation, and Erk 1/2 and
      p38 signaling. Taken together, these data suggest leptin could contribute to
      abnormal osteoblast function in OA.

PMID- 20141629
TI  - Genome-wide analysis of rice ClpB/HSP100, ClpC and ClpD genes.
AB  - BACKGROUND: ClpB-cyt/HSP100 protein acts as chaperone, mediating disaggregation
      of denatured proteins. Previous studies have shown that ClpB-cyt/HSP100 gene
      belongs to the group class I Clp ATPase proteins and ClpB-cyt/HSP100 transcript
      is regulated by heat stress and developmental cues. RESULTS: Nine ORFs were noted
      to constitute rice class I Clp ATPases in the following manner: 3 ClpB proteins
      (ClpB-cyt, Os05g44340; ClpB-m, Os02g08490; ClpB-c, Os03g31300), 4 ClpC proteins
      (ClpC1, Os04g32560; ClpC2, Os12g12580; ClpC3, Os11g16590; ClpC4, Os11g16770) and
      2 ClpD proteins (ClpD1, Os02g32520; ClpD2, Os04g33210). Using the respective
      signal sequences cloned upstream to GFP/CFP reporter proteins and transient
      expression studies with onion epidermal cells, evidence is provided that rice
      ClpB-m and Clp-c proteins are indeed localized to their respective cell locations
      mitochondria and chloroplasts, respectively. Associated with their diverse cell
      locations, domain structures of OsClpB-c, OsClpB-m and OsClpB-cyt proteins are
      noted to possess a high-level conservation. OsClpB-cyt transcript is shown to be
      enriched at milk and dough stages of seed development. While expression of OsClpB
      m was significantly less as compared to its cytoplasmic and chloroplastic
      counterparts in different tissues, this transcript showed highest heat-induced
      expression amongst the 3 ClpB proteins. OsClpC1 and OsClpC2 are predicted to be
      chloroplast-localized as is the case with all known plant ClpC proteins. However,
      the fact that OsClpC3 protein appears mitochondrial/chloroplastic with equal
      probability and OsClpC4 a plasma membrane protein reflects functional diversity
      of this class. Different class I Clp ATPase transcripts were noted to be cross
      induced by a host of different abiotic stress conditions. Complementation assays
      of Deltahsp104 mutant yeast cells showed that OsClpB-cyt, OsClpB-m, OsClpC1 and
      OsClpD1 have significantly positive effects. Remarkably, OsClpD1 gene imparted
      appreciably high level tolerance to the mutant yeast cells. CONCLUSIONS: Rice
      class I Clp ATPase gene family is constituted of 9 members. Of these 9, only 3
      belonging to ClpB group are heat stress regulated. Distribution of ClpB proteins
      to different cell organelles indicates that their functioning might be critical
      in different cell locations. From the complementation assays, OsClpD1 appears to
      be more effective than OsClpB-cyt protein in rescuing the thermosensitive defect
      of the yeast ScDeltahsp104 mutant cells.

PMID- 20141630
TI  - The EVERT (effective verruca treatments) trial protocol: a randomised controlled
      trial to evaluate cryotherapy versus salicylic acid for the treatment of
      verrucae.
AB  - BACKGROUND: Verrucae are a common, infectious and sometimes painful problem. The
      optimal treatment for verrucae is unclear due to a lack of high quality
      randomised controlled trials. The primary objective of this study is to compare
      the clinical effectiveness of two common treatments for verrucae: cryotherapy
      using liquid nitrogen versus salicylic acid. Secondary objectives include a
      comparison of the cost-effectiveness of the treatments, and an investigation of
      time to clearance of verrucae, recurrence/clearance of verrucae at six months,
      patient satisfaction with treatment, pain associated with treatment, and use of
      painkillers for the treatments. METHODS/DESIGN: This is an open, pragmatic,
      multicentre, randomised controlled trial with two parallel groups: cryotherapy
      using liquid nitrogen delivered by a healthcare professional for a maximum of 4
      treatments (treatments 2-3 weeks apart) or daily self-treatment with 50%
      salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged
      12 years and over with a verruca are being enrolled into the study. The primary
      outcome is complete clearance of all verrucae as observed on digital photographs
      taken at 12 weeks compared with baseline and assessed by an independent
      healthcare professional. Secondary outcomes include self-reported time to
      clearance of verrucae, self-reported clearance of verrucae at 6 months, cost
      effectiveness of the treatments compared to one another, and patient
      acceptability of both treatments including possible side effects such as pain.
      The primary analysis will be intention to treat. It is planned that recruitment
      will be completed by December 2009 and results will be available by June 2010.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246.

PMID- 20141632
TI  - Can differences in phosphorus uptake kinetics explain the distribution of cattail
      and sawgrass in the Florida Everglades?
AB  - BACKGROUND: Cattail (Typha domingensis) has been spreading in phosphorus (P)
      enriched areas of the oligotrophic Florida Everglades at the expense of sawgrass
      (Cladium mariscus spp. jamaicense). Abundant evidence in the literature explains
      how the opportunistic features of Typha might lead to a complete dominance in P
      enriched areas. Less clear is how Typha can grow and acquire P at extremely low P
      levels, which prevail in the unimpacted areas of the Everglades. RESULTS:
      Apparent P uptake kinetics were measured for intact plants of Cladium and Typha
      acclimated to low and high P at two levels of oxygen in hydroponic culture. The
      saturated rate of P uptake was higher in Typha than in Cladium and higher in low
      P acclimated plants than in high-P acclimated plants. The affinity for P uptake
      was two-fold higher in Typha than in Cladium, and two- to three-fold higher for
      low-P acclimated plants compared to high-P acclimated plants. As Cladium had a
      greater proportion of its biomass allocated to roots, the overall uptake capacity
      of the two species at high P did not differ. At low P availability, Typha
      increased biomass allocation to roots more than Cladium. Both species also
      adjusted their P uptake kinetics, but Typha more so than Cladium. The adjustment
      of the P uptake system and increased biomass allocation to roots resulted in a
      five-fold higher uptake per plant for Cladium and a ten-fold higher uptake for
      Typha. CONCLUSIONS: Both Cladium and Typha adjust P uptake kinetics in relation
      to plant demand when P availability is high. When P concentrations are low,
      however, Typha adjusts P uptake kinetics and also increases allocation to roots
      more so than Cladium, thereby improving both efficiency and capacity of P uptake.
      Cladium has less need to adjust P uptake kinetics because it is already efficient
      at acquiring P from peat soils (e.g., through secretion of phosphatases,
      symbiosis with arbuscular mycorrhizal fungi, nutrient conservation growth
      traits). Thus, although Cladium and Typha have qualitatively similar strategies
      to improve P-uptake efficiency and capacity under low P-conditions, Typha shows a
      quantitatively greater response, possibly due to a lesser expression of these
      mechanisms than Cladium. This difference between the two species helps to explain
      why an opportunistic species such as Typha is able to grow side by side with
      Cladium in the P-deficient Everglades.

PMID- 20141631
TI  - Brain metabolism is significantly impaired at blood glucose below 6 mM and brain
      glucose below 1 mM in patients with severe traumatic brain injury.
AB  - INTRODUCTION: The optimal blood glucose target following severe traumatic brain
      injury (TBI) must be defined. Cerebral microdialysis was used to investigate the
      influence of arterial blood and brain glucose on cerebral glucose, lactate,
      pyruvate, glutamate, and calculated indices of downstream metabolism. METHODS: In
      twenty TBI patients, microdialysis catheters inserted in the edematous frontal
      lobe were dialyzed at 1 microl/min, collecting samples at 60 minute intervals.
      Occult metabolic alterations were determined by calculating the lactate- pyruvate
      (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios. RESULTS:
      Brain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc
      were significantly reduced at brain glucose above 1 mM, reaching lowest values at
      blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral
      glutamate was measured at brain glucose 3-5 mM with a significant increase at
      brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased
      at low brain glucose levels, it was significantly decreased at brain glucose
      above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low
      brain glucose, but prevented increase in L/Glu. CONCLUSIONS: Arterial blood
      glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels
      below 1 mM are detrimental, elevated brain glucose are to be targeted despite
      increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated
      glutamate appears to be relativized by L/Glu and suggests to exclude insulin-
      induced brain injury.

PMID- 20141633
TI  - Sp1 and KLF15 regulate basal transcription of the human LRP5 gene.
AB  - BACKGROUND: LRP5, a member of the low density lipoprotein receptor superfamily,
      regulates diverse developmental processes in embryogenesis and maintains
      physiological homeostasis in adult organisms. However, how the expression of
      human LRP5 gene is regulated remains unclear. RESULTS: In order to characterize
      the transcriptional regulation of human LRP5 gene, we cloned the 5' flanking
      region and evaluated its transcriptional activity in a luciferase reporter
      system. We demonstrated that both KLF15 and Sp1 binding sites between -72 bp and 
      53 bp contribute to the transcriptional activation of human LRP5 promoter.
      Chromatin immunoprecipitation assay demonstrated that the ubiquitous
      transcription factors KLF15 and Sp1 bind to this region. Using Drosophila SL2
      cells, we showed that KLF15 and Sp1 trans-activated the LRP5 promoter in a manner
      dependent on the presence of Sp1-binding and KLF15-binding motifs. CONCLUSIONS:
      Both KLF15 and Sp1 binding sites contribute to the basal activity of human LRP5
      promoter. This study provides the first insight into the mechanisms by which
      transcription of human LRP5 gene is regulated.

PMID- 20141634
TI  - The density of macrophages in the invasive front is inversely correlated to liver
      metastasis in colon cancer.
AB  - BACKGROUND: Although an abundance of evidence has indicated that tumor-associated
      macrophages (TAMs) are associated with a favorable prognosis in patients with
      colon cancer, it is still unknown how TAMs exert a protective effect. This study
      examined whether TAMs are involved in hepatic metastasis of colon cancer.
      MATERIALS AND METHODS: One hundred and sixty cases of pathologically-confirmed
      specimens were obtained from colon carcinoma patients with TNM stage IIIB and IV
      between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen
      University. The density of macrophages in the invasive front (CD68TFHotspot) was
      scored with an immunohistochemical assay. The relationship between the
      CD68TFHotspot and the clinicopathologic parameters, the potential of hepatic
      metastasis, and the 5-year survival rate were analyzed. RESULTS: TAMs were
      associated with the incidence of hepatic metastasis and the 5-year survival rate
      in patients with colon cancers. Both univariate and multivariate analyses
      revealed that the CD68TFHotspot was independently prognostic of survival. A
      higher 5-year survival rate among patients with stage IIIB after radical
      resection occurred in patients with a higher macrophage infiltration in the
      invasive front (81.0%) than in those with a lower macrophage infiltration
      (48.6%). Most importantly, the CD68TFHotspot was associated with both the
      potential of hepatic metastasis and the interval between colon resection and the
      occurrence of hepatic metastasis. CONCLUSION: This study showed evidence that
      TAMs infiltrated in the invasive front are associated with improvement in both
      hepatic metastasis and overall survival in colon cancer, implying that TAMs have
      protective potential in colon cancers and might serve as a novel therapeutic
      target.

PMID- 20141635
TI  - A random effect multiplicative heteroscedastic model for bacterial growth.
AB  - BACKGROUND: Predictive microbiology develops mathematical models that can predict
      the growth rate of a microorganism population under a set of environmental
      conditions. Many primary growth models have been proposed. However, when primary
      models are applied to bacterial growth curves, the biological variability is
      reduced to a single curve defined by some kinetic parameters (lag time and growth
      rate), and sometimes the models give poor fits in some regions of the curve. The
      development of a prediction band (from a set of bacterial growth curves) using
      non-parametric and bootstrap methods permits to overcome that problem and include
      the biological variability of the microorganism into the modelling process.
      RESULTS: Absorbance data from Listeria monocytogenes cultured at 22, 26, 38, and
      42 degrees C were selected under different environmental conditions of pH (4.5,
      5.5, 6.5, and 7.4) and percentage of NaCl (2.5, 3.5, 4.5, and 5.5).
      Transformation of absorbance data to viable count data was carried out. A random
      effect multiplicative heteroscedastic model was considered to explain the
      dynamics of bacterial growth. The concept of a prediction band for microbial
      growth is proposed. The bootstrap method was used to obtain resamples from this
      model. An iterative procedure is proposed to overcome the computer intensive task
      of calculating simultaneous prediction intervals, along time, for bacterial
      growth. The bands were narrower below the inflection point (0-8 h at 22 degrees
      C, and 0-5.5 h at 42 degrees C), and wider to the right of it (from 9 h onwards
      at 22 degrees C, and from 7 h onwards at 42 degrees C). A wider band was observed
      at 42 degrees C than at 22 degrees C when the curves reach their upper asymptote.
      Similar bands have been obtained for 26 and 38 degrees C. CONCLUSIONS: The
      combination of nonparametric models and bootstrap techniques results in a good
      procedure to obtain reliable prediction bands in this context. Moreover, the new
      iterative algorithm proposed in this paper allows one to achieve exactly the
      prefixed coverage probability for the prediction band. The microbial growth bands
      reflect the influence of the different environmental conditions on the
      microorganism behaviour, helping in the interpretation of the biological meaning
      of the growth curves obtained experimentally.

PMID- 20141636
TI  - Variability of gene expression profiles in human blood and lymphoblastoid cell
      lines.
AB  - BACKGROUND: Readily accessible samples such as peripheral blood or cell lines are
      increasingly being used in large cohorts to characterise gene expression
      differences between a patient group and healthy controls. However, cell and RNA
      isolation procedures and the variety of cell types that make up whole blood can
      affect gene expression measurements. We therefore systematically investigated
      global gene expression profiles in peripheral blood from six individuals
      collected during two visits by comparing five of the following cell and RNA
      isolation methods: whole blood (PAXgene), peripheral blood mononuclear cells
      (PBMCs), lymphoblastoid cell lines (LCLs), CD19 and CD20 specific B-cell subsets.
      RESULTS: Gene expression measurements were clearly discriminated by isolation
      method although the reproducibility was high for all methods (range rho = 0.90
      1.00). The PAXgene samples showed a decrease in the number of expressed genes (P
      < 1*10(-16)) with higher variability (P < 1*10(-16)) compared to the other
      methods. Differentially expressed probes between PAXgene and PBMCs were
      correlated with the number of monocytes, lymphocytes, neutrophils or
      erythrocytes. The correlations (rho = 0.83; rho = 0.79) of the expression levels
      of detected probes between LCLs and B-cell subsets were much lower compared to
      the two B-cell isolation methods (rho = 0.98). Gene ontology analysis of detected
      genes showed that genes involved in inflammatory responses are enriched in B
      cells CD19 and CD20 whereas genes involved in alcohol metabolic process and the
      cell cycle were enriched in LCLs. CONCLUSION: Gene expression profiles in blood
      based samples are strongly dependent on the predominant constituent cell type(s)
      and RNA isolation method. It is crucial to understand the differences and
      variability of gene expression measurements between cell and RNA isolation
      procedures, and their relevance to disease processes, before application in large
      clinical studies.

PMID- 20141637
TI  - Pseudomonas aeruginosa cystic fibrosis isolates of similar RAPD genotype exhibit
      diversity in biofilm forming ability in vitro.
AB  - BACKGROUND: Pseudomonas aeruginosa is considered to grow in a biofilm in cystic
      fibrosis (CF) chronic lung infections. Bacterial cell motility is one of the main
      factors that have been connected with P. aeruginosa adherence to both biotic and
      abiotic surfaces. In this investigation, we employed molecular and microscopic
      methods to determine the presence or absence of motility in P. aeruginosa CF
      isolates, and statistically correlated this with their biofilm forming ability in
      vitro. RESULTS: Our investigations revealed a wide diversity in the production,
      architecture and control of biofilm formation. Of 96 isolates, 49% possessed
      swimming motility, 27% twitching and 52% swarming motility, while 47% were non
      motile. Microtitre plate assays for biofilm formation showed a range of biofilm
      formation ability from biofilm deficient phenotypes to those that formed very
      thick biofilms. A comparison of the motility and adherence properties of
      individual strains demonstrated that the presence of swimming and twitching
      motility positively affected biofilm biomass. Crucially, however, motility was
      not an absolute requirement for biofilm formation, as 30 non-motile isolates
      actually formed thick biofilms, and three motile isolates that had both flagella
      and type IV pili attached only weakly. In addition, CLSM analysis showed that
      biofilm-forming strains of P. aeruginosa were in fact capable of entrapping non
      biofilm forming strains, such that these 'non-biofilm forming' cells could be
      observed as part of the mature biofilm architecture. CONCLUSIONS: Clinical
      isolates that do not produce biofilms in the laboratory must have the ability to
      survive in the patient lung. We propose that a synergy exists between isolates in
      vivo, which allows "non biofilm-forming" isolates to be incorporated into the
      biofilm. Therefore, there is the potential for strains that are apparently non
      biofilm forming in vitro to participate in biofilm-mediated pathogenesis in the
      CF lung.

PMID- 20141638
TI  - Reproductive performance, udder health, and antibiotic resistance in mastitis
      bacteria isolated from Norwegian Red cows in conventional and organic farming.
AB  - BACKGROUND: The objectives of this study were to investigate whether there were
      differences between Norwegian Red cows in conventional and organic farming with
      respect to reproductive performance, udder health, and antibiotic resistance in
      udder pathogens. METHODS: Twenty-five conventional and 24 organic herds from
      south-east and middle Norway participated in the study. Herds were matched such
      that geographical location, herd size, and barn types were similar across the
      cohorts. All organic herds were certified as organic between 1997 and 2003. All
      herds were members of the Norwegian Dairy Herd Recording System. The herds were
      visited once during the study. The relationship between the outcomes and
      explanatory variables were assessed using mixed linear models. RESULTS: There
      were less > 2nd parity cows in conventional farming. The conventional cows had
      higher milk yields and received more concentrates than organic cows. Although
      after adjustment for milk yield and parity, somatic cell count was lower in
      organic cows than conventional cows. There was a higher proportion of quarters
      that were dried off at the herd visit in organic herds. No differences in the
      interval to first AI, interval to last AI or calving interval was revealed
      between organic and conventional cows. There was no difference between
      conventional and organic cows in quarter samples positive for mastitis bacteria
      from the herd visit. Milk yield and parity were associated with the likelihood of
      at least one quarter positive for mastitis bacteria. There was few S. aureus
      isolates resistance to penicillin in both management systems. Penicillin
      resistance against Coagulase negative staphylococci isolated from subclinically
      infected quarters was 48.5% in conventional herds and 46.5% in organic herds.
      CONCLUSION: There were no large differences between reproductive performance and
      udder health between conventional and organic farming for Norwegian Red cows.

PMID- 20141639
TI  - Homeolog loss and expression changes in natural populations of the recently and
      repeatedly formed allotetraploid Tragopogon mirus (Asteraceae).
AB  - BACKGROUND: Although polyploidy has long been recognized as a major force in the
      evolution of plants, most of what we know about the genetic consequences of
      polyploidy comes from the study of crops and model systems. Furthermore, although
      many polyploid species have formed repeatedly, patterns of genome evolution and
      gene expression are largely unknown for natural polyploid populations of
      independent origin. We therefore examined patterns of loss and expression in
      duplicate gene pairs (homeologs) in multiple individuals from seven natural
      populations of independent origin of Tragopogon mirus (Asteraceae), an
      allopolyploid that formed repeatedly within the last 80 years from the diploids
      T. dubius and T. porrifolius. RESULTS: Using cDNA-AFLPs, we found differential
      band patterns that could be attributable to gene silencing, novel expression,
      and/or maternal/paternal effects between T. mirus and its diploid parents.
      Subsequent cleaved amplified polymorphic sequence (CAPS) analyses of genomic DNA
      and cDNA revealed that 20 of the 30 genes identified through cDNA-AFLP analysis
      showed additivity, whereas nine of the 30 exhibited the loss of one parental
      homeolog in at least one individual. Homeolog loss (versus loss of a restriction
      site) was confirmed via sequencing. The remaining gene (ADENINE-DNA GLYCOSYLASE)
      showed ambiguous patterns in T. mirus because of polymorphism in the diploid
      parent T. dubius. Most (63.6%) of the homeolog loss events were of the T. dubius
      parental copy. Two genes, NUCLEAR RIBOSOMAL DNA and GLYCERALDEHYDE-3-PHOSPHATE
      DEHYDROGENASE, showed differential expression of the parental homeologs, with the
      T. dubius copy silenced in some individuals of T. mirus. CONCLUSIONS: Genomic and
      cDNA CAPS analyses indicated that plants representing multiple populations of
      this young natural allopolyploid have experienced frequent and preferential
      elimination of homeologous loci. Comparable analyses of synthetic F1 hybrids
      showed only additivity. These results suggest that loss of homeologs and changes
      in gene expression are not the immediate result of hybridization, but are
      processes that occur following polyploidization, occurring during the early (<40)
      generations of the young polyploid. Both T. mirus and a second recently formed
      allopolyploid, T. miscellus, exhibit more homeolog losses than gene silencing
      events. Furthermore, both allotetraploids undergo biased loss of homeologs
      contributed by their shared diploid parent, T. dubius. Further studies are
      required to assess whether the results for the 30 genes so far examined are
      representative of the entire genome.

PMID- 20141641
TI  - Accreditation Council for Graduate Medical Education (ACGME) annual
      anesthesiology residency and fellowship program review: a "report card" model for
      continuous improvement.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      requires an annual evaluation of all ACGME-accredited residency and fellowship
      programs to assess program quality. The results of this evaluation must be used
      to improve the program. This manuscript describes a metric to be used in
      conducting ACGME-mandated annual program review of ACGME-accredited
      anesthesiology residencies and fellowships. METHODS: A variety of metrics to
      assess anesthesiology residency and fellowship programs are identified by the
      authors through literature review and considered for use in constructing a
      program "report card." RESULTS: Metrics used to assess program quality include
      success in achieving American Board of Anesthesiology (ABA) certification,
      performance on the annual ABA/American Society of Anesthesiology In-Training
      Examination, performance on mock oral ABA certification examinations, trainee
      scholarly activities (publications and presentations), accreditation site visit
      and internal review results, ACGME and alumni survey results, National Resident
      Matching Program (NRMP) results, exit interview feedback, diversity data and
      extensive program/rotation/faculty/curriculum evaluations by trainees and
      faculty. The results are used to construct a "report card" that provides a high
      level review of program performance and can be used in a continuous quality
      improvement process. CONCLUSIONS: An annual program review is required to assess
      all ACGME-accredited residency and fellowship programs to monitor and improve
      program quality. We describe an annual review process based on metrics that can
      be used to focus attention on areas for improvement and track program performance
      year-to-year. A "report card" format is described as a high-level tool to track
      educational outcomes.

PMID- 20141640
TI  - Transcriptional profiling of Actinobacillus pleuropneumoniae during the acute
      phase of a natural infection in pigs.
AB  - BACKGROUND: Actinobacillus pleuropneumoniae is the etiological agent of porcine
      pleuropneumonia, a respiratory disease which causes great economic losses
      worldwide. Many virulence factors are involved in the pathogenesis, namely
      capsular polysaccharides, RTX toxins, LPS and many iron acquisition systems. In
      order to identify genes that are expressed in vivo during a natural infection, we
      undertook transcript profiling experiments with an A. pleuropneumoniae DNA
      microarray, after recovery of bacterial mRNAs from serotype 5b-infected porcine
      lungs. AppChip2 contains 2033 PCR amplicons based on the genomic sequence of App
      serotype 5b strain L20, representing more than 95% of ORFs greater than 160 bp in
      length. RESULTS: Transcriptional profiling of A. pleuropneumoniae recovered from
      the lung of a pig suffering from a natural infection or following growth of the
      bacterial isolate in BHI medium was performed. An RNA extraction protocol
      combining beadbeating and hot-acid-phenol was developed in order to maximize
      bacterial mRNA yields and quality following total RNA extraction from lung
      lesions. Nearly all A. pleuropneumoniae transcripts could be detected on our
      microarrays, and 150 genes were deemed differentially expressed in vivo during
      the acute phase of the infection. Our results indicate that, for example, gene
      apxIVA from an operon coding for RTX toxin ApxIV is highly up-regulated in vivo,
      and that two genes from the operon coding for type IV fimbriae (APL_0878 and
      APL_0879) were also up-regulated. These transcriptional profiling data, combined
      with previous comparative genomic hybridizations performed by our group, revealed
      that 66 out of the 72 up-regulated genes are conserved amongst all serotypes and
      that 3 of them code for products that are predicted outer membrane proteins
      (genes irp and APL_0959, predicted to code for a TonB-dependent receptor and a
      filamentous hemagglutinin/adhesin respectively) or lipoproteins (gene APL_0920).
      Only 4 of 72 up-regulated genes had previously been identified in controled
      experimental infections. CONCLUSIONS: These genes that we have identified as up
      regulated in vivo, conserved across serotypes and coding for potential outer
      membrane proteins represent potential candidates for the development of a cross
      protective vaccine against porcine pleuropneumonia.

PMID- 20141642
TI  - Demographic determinants and effect of pre-operative angiotensin converting
      enzyme inhibitors and angiotensin receptor blockers on the occurrence of atrial
      fibrillation after CABG surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) occurs in about 27% to 40% of post cardiac
      surgery patients. AF following coronary artery bypass graft surgery (CABG) is
      associated with a two-fold increase in morbidity and mortality. Various
      demographic risk factors and medications have been studied to predict the
      occurrence of this arrhythmia. The role of angiotensin related medications on the
      occurrence of AF in CABG patients is not determined. METHODS: Retrospective
      clinical and statistical analysis was made of all the patients who had undergone
      CABG surgery at Lehigh Valley Hospital during the years 2005 and 2006. Patients
      with chronic AF and those undergoing valvular surgery with CABG were excluded.
      Statistic analysis included chi-square test for categorical and student t-test
      for continuous variables. RESULTS: 757 patients (560 males and 197 females) were
      studied. AF occurred in 19% of the patients. Age (70.5 vs. 65.1, p < 0.005. OR
      per year of age: 1.02, 95%CI: 1.018-1.023) and presence of hypertension (OR:
      1.92, 95%CI: 1.086-3.140, p = 0.025) were significantly associated with
      occurrence of AF. Neither ARBs (OR: 0.78, 95%CI: 0.431-1.410, p = 0.41) nor ACE
      inhibitors (OR: 1.01, 95%CI: 0.753-1.608, p = 0.63) reduced the occurrence of
      post operative AF. Patients with post operative AF had a significantly longer
      hospital stay (9.5 +/- 5.4 days vs. 6.9 +/- 4.3 days, p = 0.001). CONCLUSIONS:
      Advanced age and presence of hypertension were independent predictors of post
      CABG AF. Patients with post operative AF had significantly longer hospital stay.
      Neither ARBs nor ACE inhibitors were associated with reduction of post-surgical
      AF. Further studies are needed to better delineate the role of angiotensin
      related medications on reduction of post-surgical AF.

PMID- 20141643
TI  - Dietary supplementation with medium-chain TAG has long-lasting cognition
      enhancing effects in aged dogs.
AB  - The present study focused on the hypothesis that dietary supplementation with
      medium-chain TAG (MCT) will improve cognitive function in aged dogs by providing
      the brain with energy in the form of ketones. Aged Beagle dogs were subjected to
      a baseline battery of cognitive tests, which were used to establish cognitively
      equivalent control or treatment groups. The dogs in the treatment group were
      maintained on a diet supplemented with 5.5 % MCT. After an initial wash-in
      period, all the dogs were tested with a battery of cognitive test protocols,
      which assessed sequentially landmark discrimination learning ability, egocentric
      visuospatial function and attention. The groups were maintained on the diets for
      8 months. The MCT-supplemented group showed significantly better performance in
      most of the test protocols than the control group. The group differences also
      varied as a function of task difficulty, with the more difficult task showing
      greater supplementation effects than the easier tasks. The group given the MCT
      supplement showed significantly elevated levels of beta-hydroxybutyrate, a ketone
      body. These results indicate, first, that long-term supplementation with MCT can
      have cognition-improving effects, and second, that MCT supplementation increases
      circulating levels of ketones. The results support the hypothesis that brain
      function of aged dogs can be improved by MCT supplementation, which provides the
      brain with an alternative energy source.

PMID- 20141644
TI  - A Q fever outbreak in a psychiatric care institution in The Netherlands.
AB  - In May 2008 the Nijmegen Municipal Health Service (MHS) was informed about an
      outbreak of atypical pneumonia in three in-patients of a long-term psychiatric
      institution. The patients had been hospitalized and had laboratory confirmation
      of acute Q fever infection. The MHS started active case finding among in
      patients, employees of and visitors to the institution. In a small meadow on the
      institution premises a flock of sheep was present. One of the lambs in the flock
      had been abandoned by its mother and cuddled by the in-patients. Samples were
      taken of the flock. Forty-five clinical cases were identified in employees, in
      patients and visitors; 28 were laboratory confirmed as Q fever. Laboratory
      screening of pregnant women and persons with valvular heart disease resulted in
      one confirmed Q fever case in a pregnant woman. Of 27 samples from animals, seven
      were positive and 15 suspect for Coxiella burnetii infection. This outbreak of Q
      fever in a unique psychiatric setting pointed to a small flock of sheep with
      newborn lambs as the most likely source of exposure. Care institutions that have
      vulnerable residents and keep flocks of sheep should be careful to take adequate
      hygienic measures during delivery of lambs and handling of birth products.

PMID- 20141645
TI  - Molecular and spatial epidemiology of human campylobacteriosis: source
      association and genotype-related risk factors.
AB  - The epidemiology of human campylobacteriosis is complex but in recent years
      understanding of this disease has advanced considerably. Despite being a major
      public health concern in many countries, the presence of multiple hosts,
      genotypes and transmission pathways has made it difficult to identify and
      quantify the determinants of human infection and disease. This has delayed the
      development of successful intervention programmes for this disease in many
      countries including New Zealand, a country with a comparatively high, yet until
      recently poorly understood, rate of notified disease. This study investigated the
      epidemiology of Campylobacter jejuni at the genotype-level over a 3-year period
      between 2005 and 2008 using multilocus sequence typing. By combining
      epidemiological surveillance and population genetics, a dominant, internationally
      rare strain of C. jejuni (ST474) was identified, and most human cases (65.7%)
      were found to be caused by only seven different genotypes. Source association of
      genotypes was used to identify risk factors at the genotype-level through
      multivariable logistic regression and a spatial model. Poultry-associated cases
      were more likely to be found in urban areas compared to rural areas. In
      particular young children in rural areas had a higher risk of infection with
      ruminant strains than their urban counterparts. These findings provide important
      information for the implementation of pathway-specific control strategies.

PMID- 20141646
TI  - Reflection paper on MRSA in food-producing and companion animals: epidemiology
      and control options for human and animal health.
AB  - The scope of this reflection paper was to review the latest research on the risk
      of MRSA infection and colonization in animals. Attention focused on occurrence,
      risk factors for colonization and infection, and human contact hazard for
      livestock, horses, and companion animals. Whereas the clonal relationship between
      MRSA strains of CC398 is straightforward in livestock this is less obvious in
      horses. Small companion animals typically share MRSA strains that seem to
      exchange with a human reservoir. Management and therapeutic options have been
      suggested for livestock, horses, companion animals, as well as instructions on
      safety measures for persons in contact with animals. Conclusions were drawn with
      emphasis on future research activities, especially to confirm the apparent
      evolution of the organism and to demonstrate efficiency of control strategies.

PMID- 20141647
TI  - High prevalence of nasal MRSA carriage in slaughterhouse workers in contact with
      live pigs in The Netherlands.
AB  - Livestock-associated MRSA has been found in various animals, livestock farmers
      and retail meat. This study aimed to determine the prevalence and determinants of
      nasal MRSA carriage in pig slaughterhouse workers. Three large pig
      slaughterhouses in The Netherlands were studied in 2008 using human and
      environmental samples. The overall prevalence of nasal MRSA carriage in employees
      of pig slaughterhouses was 5.6% (14/249) (95% CI 3.4-9.2) and working with live
      pigs was the single most important factor for being MRSA positive (OR 38.2,
      P<0.0001). At the start of the day MRSA was only found in environmental samples
      from the lairages (10/12), whereas at the end of the day MRSA was found in the
      lairages (11/12), the dirty (5/12) and clean (3/12) areas and green offal (1/3).
      The MRSA status of the environmental samples correlated well with the MRSA status
      of humans working in these sections (r=0.75). In conclusion, a high prevalence of
      nasal MRSA carriage was found in pig-slaughterhouse workers, and working with
      live pigs is the most important risk factor. Exact transmission routes from
      animals to humans remain to be elucidated in order to enable application of
      targeted preventive measures.

PMID- 20141648
TI  - The spatial distribution of campylobacteriosis in New Zealand, 1997-2005.
AB  - In New Zealand Campylobacter infection rates have increased steadily since 1980,
      reaching a peak in 2003 (396/100,000 population). Compared to other nations,
      disease rates are unfavourably high (e.g. Australia 117/100,000 population, UK
      85/100,000 population, USA 13/100,000 population). This ecological study
      investigated spatial variations in Campylobacter infection rates across New
      Zealand's Territorial Local Authorities (TLAs, n=73) for the period 1997-2005.
      Applying multiple linear regression, we examined whether geographical factors
      such as socio-demographic characteristics, climate, land use, water and the food
      environment were associated with local differences in the occurrence of
      Campylobacter infection rates. The results suggested significant variations in
      campylobacteriosis across TLAs (average annual rates ranging from 97 to
      526/100,000 population), with higher rates in the South Island. Disease rates
      were associated with lower socio-economic deprivation (P<0.01), the proportion of
      the population aged 25-44 years (P<0.01) and fresh food outlet density (P<0.76).
      The results underline the role of area-level characteristics in explaining the
      spatial distribution of campylobacteriosis in New Zealand. In particular, the
      findings draw attention to the relatively unexplored role of fresh food outlets
      as a potential risk factor for increased Campylobacter notifications.

PMID- 20141649
TI  - Coping with stress through decisional control: quantification of negotiating the
      environment.
AB  - Coping with stress through 'decisional control' - positioning oneself in a
      multifaceted stressing situation so as to minimize the likelihood of an untoward
      event - is modelled within a tree-structure scenario, whose architecture
      hierarchically nests elements of varying threat. Analytic and simulation
      platforms quantify the game-like interplay of cognitive demands and threat
      reduction. When elements of uncertainty enter the theoretical structure,
      specifically at more subordinate levels of the hierarchy, the mathematical
      expectation of threat is particularly exacerbated. As quantified in this model,
      the exercise of decisional control is demonstrably related to reduction in
      expected threat (the minimum correlation across comprehensive parameter settings
      being .55). Disclosure of otherwise intractable stress-coping subtleties, endowed
      by the quantitative translation of verbal premises, is underscored. Formalization
      of decisional stress control is seen to usher in linkages to augmenting formal
      developments from fields of cognitive science, preference and choice modelling,
      and nonlinear dynamical systems theory. Model-prescribed empirical consequences
      are stipulated.

PMID- 20141650
TI  - [History, anthropology and medicine].

PMID- 20141651
TI  - [Mycetoma in prehispanic Mexico. Review in the skeletical collection of Tlatilco
      culture].
AB  - In this text, we described a case of mycetoma (an osteophylic mycotic disease)
      found in the Tlatilco skeletal collection. The osseous lesions presented the
      characteristic features for the diagnosis of mycetoma. It had clinical
      similarities with the actual prevalence features. The topic Tlatilco culture
      included ecosystem characteristics and daily activities proper for this culture,
      showing and comparing the uncertainty of this disease nowadays.

PMID- 20141652
TI  - [The empacho in Mexico during the nineteenth century].
AB  - During the 19th century, empacho as a nosological entity prompted academic
      research by such renowned Mexican clinicians as Miguel F. Jimenez, Eduardo
      Liceaga, Fernando Altamirano, Jose Peon y Contreras, among others. Empacho is
      often the result of excessive eating or difficulty in digestion of certain foods,
      especially fruits with a peel (oranges, limes, grapefruits, apples, etc.) and
      legumes (beans, sweet pea, chick peas). Empacho has a greater effect on children
      under the age of two. It is clinically identified by diarrhea, abdominal pain,
      fever, restlessness, the presence of abdominal distension, abdominal dullness to
      percussion, nausea, vomiting, anorexia and meteorism. The most common treatments
      during the 19th century sought to evacuate gastrointestinal content immediately
      through vomiting or purgative medication. The general population often used
      medicinal plants to provoke gastrointestinal purges, while academic doctors most
      frequently used castor oil as a laxative and ipecacuanha to induce vomiting. This
      work presents a description and analysis of the general characteristics of the
      popular illness, empacho. The information comes from doctors, pharmacists,
      homeopaths, botanists and popular groups.

PMID- 20141653
TI  - [Tlaloc and ascites].
AB  - Ascites has been a common pathological sign among prehispanic Mexican people, as
      a result from hepatic and cardiac ailments. In this sense it represents a
      significant epidemiological problem. But it also is important because is related
      to Tlaloc and the rain gods and goddesses. The hidropic body is a symbolic water
      container and have a special function: serve as a Tlaloc and related gods vehicle
      to transport the precious liquid. In this paper we analyze the Tlaloc role as
      water and alimentary substances provider and his capital importance for people
      survival. We also describe five different plastic ways to represent water in the
      body, all of them with clear relationships to Tlaloc.

PMID- 20141654
TI  - [Critical reading of investigative reports by nutrition students].
AB  - BACKGROUND: From the perspective of participative education, the critical reading
      of investigative reports can be developed from the first formation year. The
      objective was to evaluate the effect of an educational strategy to promote the
      participation in the development of attitudes for critical reading in the first
      semester of a technical career. METHODS: An instrument to determine the aptitude
      development was developed, validated and applied. It included comprehension,
      interpretation, judgment and proposal indicators. The educational strategy was
      implemented through discussion seminars, and promoted student participation.
      RESULTS: The median and the interpretation indicator increased from 38 to 56 and
      from 12 to 19 points, respectively (p < 0.05). The developmental aptitude of
      critical reading was increased 25% in all students. CONCLUSIONS: Promotion of an
      educational participation strategy favors the aptitude for critical reading of
      investigation reports in a group of students in the first semester of their
      nutrition career.

PMID- 20141655
TI  - [Risk factors for dental fluorosis in children between 6 and 15 years old].
AB  - OBJECTIVE: To identify risk factors for dental fluorosis in children between 6
      and 15 years. METHODS: A cross-sectional survey in 1284 students between 6 and 15
      years from four living areas. Presence and degree of dental fluorosis were
      investigated by using the classification of Dean, tooth decay and variables like
      source of water consumption, juices, prepared gaseous drinks, tea, types of
      dental paste used, and periodic applications of fluoride. Descriptive statistics
      and chi(2) test were applied. RESULTS: The prevalence of fluorosis was 52.6 %,
      (very slight 45.5 %, slight 40.0 %, moderate 11.8 %, and severe 2.6 %). Tooth
      decay appeared in 52.7 % of the total of cases studied. The variables with more
      significant differences were the presenting age (the greater fluorosis in
      children was from 8 to 14 years), tea, juice and prepared gaseous drink
      consumption, the periodic application of fluoride and the area of residence,
      varying from 45 to 61 % of fluorosis between the areas of residence. All of these
      had p < 0.05. CONCLUSIONS: Prepared gaseous drink and tea consumption, age in
      relation to the exhibition of periodic applications of fluoride and the area of
      residence are the main risk factors for dental fluorosis.

PMID- 20141656
TI  - [The cross-sectional area of the median nerve by sonography in the diagnosis of
      carpal tunnel syndrome].
AB  - OBJECTIVE: To measure the median nerve cross-sectional area (MNCSA) at the carpal
      tunnel (CT) level by sonography (S) in a Mexican population. METHODS: A
      comparative cross-sectional design study with a nonprobabilistic sampling with 50
      women and 50 men in good health were submitted for measuring MNCSA at the level
      of the CT. Other variables like sex; side and degree of daily hand activity were
      also studied. The analysis was made by descriptive statistics, and Mann-Whitney U
      or Kruskal-Wallis tests. RESULTS: The mean MNCSA was 0.063 +/- 0.015 cm(2), in
      women; in men it was 0.072 +/- 0.018 cm(2); the difference was significant (p <
      0.004). The median MNCSA among women was 0.062 cm(2) in the right side and 0.060
      cm(2) in the left (90th percentile for both hands of 0.084 cm(2)); in men, it was
      of 0.070 cm(2) in the right hand and of 0.069 cm(2) in the left (90th percentile
      for both hands of 0.097 cm(2)). The difference between women and men was
      significant in each side, but not between right and left hands (p = 0.21). There
      was no correlation between age and MNCSA on either side, or with hand activity.
      CONCLUSIONS: A MNCSA value of 0.1 cm(2) for men and 0.09 cm(2) for women is
      proposed as a standard parameter for the Mexican population.

PMID- 20141657
TI  - [Risk factors for cognitive and functional impairment in the elderly].
AB  - OBJECTIVE: To establish association between cognitive and functional impairment
      with economic, social and demographic factors, chronic disease and multidrug
      therapy in the aged patient. METHODS: A cross-sectional study was carried out in
      2002 with 422 individuals 60 years old and older. A questionnaire for exploring
      social and economic conditions was applied. Folsteins' mini-mental exam and Katz,
      Lawton and Bronfman instruments were also applied. A bivariate analysis was
      performed to select variables for logistic regression (p = 0.20 in a chi(2)).
      Adjusted odds ratios were used to estimate association. RESULTS: There were 422
      individuals interviewed, 178 were male and 244 female, with a mean age of 68
      years. The factors associated with cognitive impairment were stroke, female
      gender, and social and economic level. For daily activities diabetes mellitus 2
      and for daily instrumental activities the associations were female gender, visual
      impairment and multi-drug therapy, all with p < 0.05. CONCLUSIONS: Some factors
      can prevent the presence of cognitive and functional impairment in the elderly.

PMID- 20141658
TI  - [Epidemiology of dermatosis in geriatric patients].
AB  - OBJECTIVE: To describe and compare the skin diseases in elderly attended at the
      geriatric service with those attended at the dermatology service. METHODS: The
      study was carried out on 100 elderly patients attended at the geriatrics service
      of nonskin disease and 100 elderly patients attended at the dermatology service.
      The sampling was of consecutive cases. Skin phototype and photo-aging were
      determined. The type and frequency of the dermatosis were described. RESULTS: All
      the patients presented at least one dermatosis with an average of five lesions.
      There was no difference between the main dermatologic causes for consultation in
      either service. The most frequent phototype was type IV, and when it was
      correlated with the degree of photo damage measured with the Glogau scale, it was
      type III. In relation to dermatoses that require treatment we found: actinic
      keratitis, onychatrophia, xerosis, prurigo and vasculocutaneous complex. The most
      frequent dermatose found on physical exam were: solar lentigos, seborrheic
      keratitis, Favre-Racouchot disease, cherry angiomas, guttata hypomelanosis.
      CONCLUSIONS: Elderly patients attended at the geriatric and dermatology services
      presented similar skin diseases.

PMID- 20141659
TI  - [The Flugge's drops].

PMID- 20141660
TI  - [Guideline for integrated geriatric assessment].
AB  - A clinical practice guideline was developed as a response to the increasing of
      elderly in Mexican population due to the epidemiological transition; this
      instrument allows the assessment of health conditions for people from 60 years of
      age and older, and it can be a tool for helping family physicians and nurses in
      providing care for the main health problems of this group of age. The guideline
      for gerontologic assessment includes six principal health priorities in older
      people (loss of vision, difficulty to hear, falls or problems walking,
      nutritional disorders, memory difficulties, and sleep disorders); additionally,
      another four components for assessment are revised (medication use, physical
      functionality, quality of life, and social support). Simple recommendations for
      detection, diagnosis and management of these problems in primary care settings
      are presented.

PMID- 20141661
TI  - [Treatment of macroprolactinoma with cabergoline during pregnancy].
AB  - OBJECTIVE: Management of macroprolactinomas in women who plan to get pregnant is
      controversial and when this happen there is a risk of pituitary enlargement, if
      this happens bromocriptine has a safe profile to be used during pregnancy, but if
      it is not tolerated cabergoline is a good alternative. CLINICAL CASES: We
      describe two patients with macroprolactinomas who intended to get pregnant. One
      of them had been previously treated surgically and the second one was treated
      with bromocriptine and got pregnant before the tomographic studies were checked.
      Both patients developed during pregnancy symptoms of macroprolactinoma
      enlargement and were initially treated with bromocriptine but this was not
      tolerated and were switched to cabergoline. Both pregnancies ended with a normal
      full term newborn. CONCLUSION: Pregnant women with symptoms of pituitary
      enlargement must be treated with bromocriptine, but if it is not tolerated
      cabergoline is a good choice.

PMID- 20141662
TI  - [Relationship between functional social support and vital satisfaction in the
      elderly].
AB  - BACKGROUND: To determine the relationship between functional social support and
      vital satisfaction of the elder retirement adult. METHODS: Comparative cross
      sectional study in retired adults aged 60 years and more. Two groups were
      integrated (high and low satisfaction) evaluated with Moral Scale of Satisfaction
      of the Geriatric Center of Philadelphia modified and validated by Montorio. The
      sample size was calculated with comparative cross-sectional studies formula,
      presence of the social support of 80 % in the group of high satisfaction and 50 %
      in the one of low satisfaction (n = 29). The selection was made at random using
      the payroll listing of retirees. Social demographic variables were studied.
      Relationship between the retirement and functional social support was evaluated
      with the scale of Functional Social Support of Duker-UNC-11. RESULTS:
      Sociodemographic characteristics and those related to the retirement did not
      present significant statistical differences (p > 0.05) in the groups of high and
      low satisfaction. There was an association between the functional social support
      and the vital satisfaction with odds ratio of 3.00 (95%CI = 1.08-8.32).
      CONCLUSIONS: Functional social support and vital satisfaction in the elderly were
      associated.

PMID- 20141663
TI  - [Further than learning contents, developing skills].
AB  - OBJECTIVE: To evaluate the scope of an educational strategy for developing an
      aptitude for critical reading of educational research information (CRERI) and for
      clinical research information (CRCRI). METHODS: A longitudinal, intervening,
      comparative study was performed on seven groups with educational interventions
      that promote development skills rather than learning contents. This was evaluated
      through two instruments that measure skills for critical reading information from
      educational and clinical investigation reports. RESULTS: Significant differences
      were encountered favorable to CRCRI, among the initial and final evaluation of
      students in a whole manner (p < 0.001). Group analysis showed differences until
      the end of educational interventions in three of them (p < 0.01). CONCLUSIONS:
      The educational strategy had two favorable effects on the CRCRI; nevertheless the
      educational interventions were solely aimed at promoting CRERI. The extension
      from one to another aptitude was shown to be independent of contents. This
      strategy can be an alternative for encouraging students to self-learning, which
      leads to a better usage of available information sources.

PMID- 20141664
TI  - [Human trichinosis. A case simulating polymyositis].
AB  - The human trichinosis is a cosmopolitan rare zoonosis in Mexico. It presents
      clinically, with an infectious toxic pattern. Typical symptomatology includes:
      fever, diarrhea, facial edema and myalgias, which can resemble other illnesses
      like typhoid fever, angioneurotic edema, septicemia, rheumatic disease-like
      vasculitis and dermato-polymyositis. The treatment is based on the use of
      antiparasites. In this paper a trichinosis case is described in a woman, 29 years
      old who lives in the metropolitan area, with a clinical pattern that suggest
      polymyositis. The diagnosis was confirmed through a muscle biopsy. The treatment
      was albendazole and prednisone with successful results.

PMID- 20141665
TI  - [Giant mediastinal neurilemoma. A case report].
AB  - BACKGROUND: Mediastinal neurilemmoma is an infrequent and a big size neoplasm in
      the posterior mediastinum. There are usually no symptoms. When there is a
      pressure against nerves or vascular structures, it can be dangerous for the life.
      The main problem of this tumors is the diagnosis: surgical approach and the
      complete resection without injuring vital mediastinal structures. CLINICAL CASE:
      We report a case in a 29-year-old male with a giant mediastinal neurilemmoma. He
      had chest pain for two months. Chest rays showed opacity in the left chest. A
      broncofiberscopy, computed tomography and transthoracic biopsy were performed.
      Finally, the patient had a left posterolateral thoracotomy. CONCLUSIONS: The
      giant mediastinal neurilemmoma is a benign and asymptomatic neoplasm in most
      cases. When the symptoms are present, they are nonspecific. We should rule out
      other pathologies. The intraoperatory fiberscopy is useful for the resection of
      small mediastinal tumours.

PMID- 20141666
TI  - [Use of medicinal plants during pregnancy].
AB  - BACKGROUND: Plants have been used by humans since the ancient times, for eating,
      for clothing and for curing illnesses. The noxious effects of many medicinal
      plants are still ignored, mainly during pregnancy. OBJECTIVE: To identify the use
      of medicinal plants (MP) in pregnant women in primary care medicine. METHODS: A
      descriptive, prospective study was carried out in 300 pregnant women from two
      primary care clinics. They were interviewed to identify the use of MP, the age of
      the pregnancy which MP were more used with and the medical indication for its
      use. RESULTS: The most frequent trimester of consumption of MP was the first. The
      most MP ingested were the Japanese mentha (Mentha arvensis), the linden (Justicia
      pectoralis), the verbena (Stachytarpheta jamaicensis) and the anison (Piper
      auritum). A high prevalence of consumption of MP did not have medical indication.
      CONCLUSIONS: The frequent use of MP during pregnancy shows a lack of information
      about their risks for pregnancy. Several studies of MP showed abortive,
      teratogenic potential and cytotoxic properties. It is necessary to educate
      pregnant women to avoid self-medication with MP.

PMID- 20141667
TI  - [Leech hirudo medicinalis: a therapeutic alternative available in Mexico].
AB  - Throughout history a diversity of therapeutic properties have been attributed to
      the leech Hirudo medicinalis, however, during the past twenty years its use has
      proven to be a practical and effective method for the relief of venous
      engorgement in reconstructive surgery. In Mexico this practice has been limited
      due to the lack of supply and to the time-consuming process of importation. Based
      on this need, the animal facilities of the Occidental Biomedical Research Center
      IMSS in Guadalajara, Jalisco, has initiated a breeding and reproduction program
      of this species with the aim at improving its availability as a therapeutic
      device. The salivary gland of Hirudo medicinalis contains one of the most potent
      natural anticoagulants, known as hirudin, a histamine-like vasodilator, platelet
      aggregation inhibitors and highly specific proteases, all of which favor venous
      flow and turn this species into the most useful in the clinical setting.
      Nevertheless, it is important to know the potential risks of leech therapy since
      it has been associated with considerable morbidity when adequate precautions are
      not taken. This review exposes relevant aspects of the medicinal leech, the
      indications, mechanism of action and the protocol for this therapy.

PMID- 20141668
TI  - [Pneumonia and its social representations].
AB  - OBJECTIVE: To correlate the sociostructural variables with the knowledge about
      pneumonia and to explore the social representations about the etiology,
      prevention, development and treatment in poor communities. METHODS: A survey in
      848 adults from seven Rural Health Centers affiliated to IMSS-Oportunidades
      Program in four States, was carried out. RESULTS: One-third of the sample did not
      understand the term pneumonia; 35 % of the patients with risk factors did not
      know its etiology; 43 % did not know about associated complications but 85 %
      considered that it causes death. The use of antibiotics was recognized as a
      therapeutic measure by 78 % and 20 % did not know how to prevent pneumonia.
      CONCLUSION: The findings showed a positive attitude to immunization but
      inadequate information about respiratory diseases. In neighborhoods with
      insufficient public services (purified water, electricity and paved roads) the
      ignorance about pneumonia tended to increase.

PMID- 20141669
TI  - Introduction: addressing challenges in multiple myeloma management in an era of
      new therapeutics.

PMID- 20141670
TI  - Complications of multiple myeloma therapy, part 2: risk reduction and management
      of venous thromboembolism, osteonecrosis of the jaw, renal complications, and
      anemia.
AB  - Venous thromboembolism (VTE), osteonecrosis of the jaw, renal failure, and anemia
      are all common complications of multiple myeloma therapy. Many of these adverse
      events have been documented only in the past 5 to 10 years, in conjunction with
      the introduction of a series of the newer therapies thalidomide, bortezomib, and
      lenalidomide. This article discusses these complications in detail and provides
      strategies for health care providers to best prevent, identify, and manage them.
      Preventive measures, such as VTE prophylaxis and appropriate dental hygiene, as
      well as patient education, dose adjustments, limited duration of drug treatment,
      and consideration of therapies that are associated with less burdensome adverse
      event profiles, can contribute to substantially improved outcomes and quality of
      life.

PMID- 20141671
TI  - The role of maintenance therapy in the treatment of multiple myeloma.
AB  - Maintenance therapy in multiple myeloma has been under investigation for more
      than 3 decades, without evidence of clear benefit until recently. Chemotherapy
      maintenance offers no benefit after conventional or high-dose treatment.
      Interferon-based maintenance is associated with minimal improvements in clinical
      outcomes, but is poorly tolerated. Results of corticosteroid maintenance studies
      have been conflicting; at least one randomized trial showed improved survival
      with prednisone maintenance after conventional chemotherapy. The role of the
      novel agents thalidomide, lenalidomide, and bortezomib as maintenance is
      emerging. Most reported maintenance studies have evaluated thalidomide, alone or
      in combination with a corticosteroid. Several of these studies suggest that
      thalidomide-based maintenance prolongs overall survival after autologous stem
      cell transplantation. Important questions that have not yet been resolved include
      the optimal dose and duration of thalidomide, whether clinical benefit depends on
      response to induction therapy and risk for relapse, and whether reported benefits
      are caused by cytoreduction or eradication of minimal residual disease,
      especially with bortezomib maintenance. Ongoing randomized trials are evaluating
      lenalidomide and bortezomib maintenance therapies to better define the role of
      these drugs as maintenance in multiple myeloma.

PMID- 20141672
TI  - In the age of novel therapies, what defines high-risk multiple myeloma?
AB  - Multiple myeloma is characterized by clinical and biologic heterogenicity.
      Recently, genetic analysis has provided predictable prognosis across different
      types of treatment. These advances have allowed patients to be categorized into
      different risk groups and have been particularly useful in defining a high-risk
      group with short survival after standard- and high-dose chemotherapies.
      Preliminary studies have shown promising outcomes after the use of novel agents,
      such as bortezomib, thalidomide, and lenalidomide in high-risk patients,
      including those eligible for autologous stem cell transplantation and those who
      cannot or will not undergo transplantation. The application of risk-based therapy
      and the potential of the new agents to abrogate the influence of adverse
      prognostic features may improve outcomes in these patients.

PMID- 20141673
TI  - Complications of multiple myeloma therapy, part 1: risk reduction and management
      of peripheral neuropathy and asthenia.
AB  - Peripheral neuropathy (PN) and asthenia (fatigue) occur as both disease- and
      treatment-related complications in patients with multiple myeloma (MM). Risk
      factors for treatment-related PN, which has an estimated incidence of 37% to 83%
      among patients with MM, include therapy duration, dose intensity, cumulative
      dose, and the presence of preexisting neuropathy. Asthenia is the most common
      adverse effect of treatment, occurring in approximately 76% to 96% of patients
      receiving therapy. The severity of PN and asthenia can range from mild to
      potentially debilitating. These conditions can be dose limiting; they may
      interfere with optimizing duration of therapy and may also substantially affect
      patient quality of life. Regular screening and monitoring, combined with patient
      education and effective management strategies, can reduce the risk of these
      treatment-related complications, as well as their consequences.

PMID- 20141674
TI  - The 2010 NCCN clinical practice guidelines in oncology on prostate cancer.

PMID- 20141675
TI  - A method for using life tables to estimate lifetime risk for prostate cancer
      death.
AB  - Prostate cancer can have a long and indolent course, and management without
      curative therapy should be considered in select patients. When counseling
      patients, a useful way to convey the risk for death from competing causes is to
      estimate their lifetime risk for dying from prostate cancer. Double-decrement
      life tables were constructed to calculate age-specific death rates using the
      death probabilities from the Social Security Administration life tables and
      Gleason score-specific mortality rates reported from a pre-PSA cohort study. The
      lifetime risk for prostate cancer death was calculated. Life tables provided life
      expectancy and risk for prostate cancer death based on age at diagnosis. For
      example, a 60-year-old patient with a Gleason score 6, 7, or 8 tumor had an
      overall life expectancy of 14.4, 10.2, or 6.6 years, respectively. The risk for
      prostate cancer death during the expected years of life was 33%, 49%, or 57%,
      respectively. If a 10-year lead-time bias was assumed for PSA detection, the
      risks for death from prostate cancer decreased to 16%, 26%, or 37%, respectively.
      If the patient was in the bottom quartile for overall health and disease was
      detected by prostate examination, the risk for death from prostate cancer was
      21%, 32%, or 40%, respectively. A Web-based tool for performing these
      calculations is available at
      http://www.roswellpark.org/Patient_Care/Specialized_Services/Prostate_Cancer_Esti
      ator.html. Life tables can be created to estimate overall life expectancy and
      risk for prostate cancer death, and to assist with decision-making when
      considering management without curative therapy.

PMID- 20141676
TI  - NCCN clinical practice guidelines in oncology: prostate cancer.

PMID- 20141677
TI  - Appropriate use of nomograms to guide prostate cancer treatment selection.
AB  - For decades physicians have attempted to accurately predict post-treatment
      outcomes before performing prostate cancer interventions. Use of basic clinical
      factors, such as clinical T-stage, biopsy Gleason sum, and pretreatment prostate
      specific antigen, has allowed some level of prediction of pathologic and clinical
      outcomes. However, these basic tables and risk stratification schema provide a
      broad range of potential outcomes. The rapid growth of retrospective research in
      prostate cancer has yielded an abundance of additional potential prognostic
      factors that may influence outcomes of interest; however, incorporating and
      understanding the significance of these ever-expanding factors is difficult for
      even the most experienced physicians. Nomograms incorporate these factors
      (including treatment-specific) and assign them relative weights to provide a
      probability of the outcome of interest on a graphical scale. They distill large
      numbers of data into a manageable format and provide the probability of outcomes
      on a continuous scale rather than in categoric groups. However, because they
      require a computation to generate a probability, they are not amenable to
      memorization, which decreases ease of use. Furthermore, these numbers still have
      associated confidence intervals and the models are largely derived from
      retrospective data, which have inherent drawbacks. Clinicians and patients should
      still exercise due diligence when interpreting the results of these nomograms,
      and these prediction tools should not serve as a stand-alone substitute for
      clinical decision-making.

PMID- 20141679
TI  - Salvage or adjuvant radiation therapy: counseling patients on the benefits.
AB  - Recent developments in the urologic oncology literature suggest that residual
      local disease--as opposed to the presence of occult metastases at surgery--may
      characterize a more substantial component of the natural history of the
      recurrence and progression of initially clinically localized prostate cancer than
      previously appreciated. These important studies have illuminated the extent to
      which postoperative radiotherapy (RT) may provide benefit to patients with
      adverse pathologic features (extraprostatic extension, seminal vesicle invasion,
      or positive surgical margins) or biochemical recurrence after radical
      prostatectomy. Nevertheless, the question of whether all patients with the
      aforementioned adverse features should undergo immediate adjuvant RT versus
      initial observation with more selective--but early--salvage RT in the event of
      biochemical failure remains the subject of heated controversy. This article
      reviews salient recent studies in this field to address important questions
      relevant to counseling patients on the use of postprostatectomy RT. Discussion
      points include data supporting benefit (efficacy), questions of generalizability
      of benefit (effectiveness) and risks, and important questions for further study.

PMID- 20141678
TI  - Adverse effects of androgen deprivation therapy: defining the problem and
      promoting health among men with prostate cancer.
AB  - Androgen deprivation therapy (ADT) plays a central role in the management of men
      with locally advanced, recurrent, and metastatic prostate cancer. Because most
      men diagnosed with prostate cancer will die of something other than their cancer,
      treatment-related adverse effects are highly relevant to their long-term health.
      Benefits of ADT in each clinical setting must be weighed against ADT-related
      adverse effects. ADT is detrimental to several metabolic end points and to bone
      health. ADT has been prospectively shown to cause decreased lean muscle mass,
      increased fat mass, weight gain, increased cholesterol and triglycerides, insulin
      resistance, and loss of bone mineral density. In population-based analyses it has
      been associated with an increased incidence of diabetes, clinical fractures, and
      cardiovascular disease. Data-driven recommendations for managing these adverse
      effects are needed. Currently the authors advocate the use of adapted practice
      guidelines developed to prevent diabetes, fractures, and coronary heart disease
      in the general population.

PMID- 20141680
TI  - NCCN clinical practice guidelines in oncology: prostate cancer early detection.

PMID- 20141681
TI  - Prostate cancer screening and determining the appropriate prostate-specific
      antigen cutoff values.
AB  - Prostate-specific antigen (PSA) in combination with digital rectal examination
      forms the basis for current prostate cancer (CaP) screening programs. Although
      PSA screening was recently shown to reduce CaP-specific mortality in the European
      randomized trial, its limitations include the risk for unnecessary prostate
      biopsy and the diagnosis and treatment of some CaP that might never have caused
      suffering or death. A potential way to minimize these pitfalls is through the use
      of derivatives of PSA, particularly PSA kinetics, to increase the specificity for
      clinically relevant CaP. CaP is the second-leading cause of cancer death in men
      in the United States and many other westernized countries; accordingly, judicious
      screening of healthy men allows for diagnosis sufficiently early that all options
      (i.e., treatment or surveillance) are still available in most cases.

PMID- 20141682
TI  - Use of nomograms for early detection in prostate cancer.
AB  - Since the first introduction of prostate-specific antigen (PSA) as a screening
      tool in the 1980s, the accurate diagnoses of clinically significant prostate
      cancer remains a challenge. Analysis of a correlation between PSA levels and
      prostate biopsies of men with PSA 3 ng/mL or less in the placebo group of the
      Prostate Cancer Prevention Trial suggested that no "normal" PSA level exists.
      With the acknowledgement that PSA level is considered a continuum rather than a
      dichotomous marker, accurately diagnosing clinically significant prostate cancer
      is even more challenging. Nomograms are increasingly being used as tools in the
      clinical setting to address this challenge. Through incorporating multiple
      clinical factors, such as PSA, digital rectal examination, age, race, prostate
      volume, family history, and previous negative biopsy, risk calculators can
      improve sensitivity of diagnosis over using a PSA cutoff alone. This article
      discusses the rational for the use of nomograms and the advantages and
      limitations for the most commonly used nomograms.

PMID- 20141683
TI  - Forensic odontology.

PMID- 20141684
TI  - Coronary anomalies in Pakistani children with tetralogy of Fallot.
AB  - OBJECTIVE: To determine coronary artery anomalies in tetralogy of Fallot in
      Pakistani children as seen on angiography. STUDY DESIGN: Case series. PLACE AND
      DURATION OF STUDY: The National Institute of Cardiovascular Diseases, Karachi,
      Pakistan from July 2006 to July 2007. METHODOLOGY: Children under 15 years of age
      with echocardiographic diagnosis of tetralogy of Fallot were included in the
      study. All patients had pre-operative cardiac catheterization and angiography.
      Coronary arteries were studied with a nonselective aortic root angiogram in
      standard cranially tilted left anterior oblique view. The frequency of a normal
      and an anomalous coronary was determined. RESULTS: Of the 83 patients, 78% were
      male and had a mean age of 8.9 years. Their mean weight was 14.3 kilograms.
      Seventy six (91.6%) had a normal coronary anatomy while 7 (8.4%) patients had
      anomalous coronary arteries. Among the patients with coronary anomalies, the
      commonest was a single origin coronary artery in 04 (57.14%) cases. Three
      (42.86%) had an anomalous origin of left anterior descending artery from the
      right coronary artery. CONCLUSION: Coronary artery anomalies were detected in
      8.4% of the cases with tetralogy of Fallot. Single origin coronary artery anomaly
      was the commonest anomaly.

PMID- 20141686
TI  - Dietary pattern, height, weight centile and BMI of affluent school children and
      adolescents from three major cities of Pakistan.
AB  - OBJECTIVE: To compare the dietary pattern, height, weight centile and BMI of
      affluent school children and adolescents from three major cities of Pakistan.
      STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Private Schools
      of Karachi, Quetta and Lahore, from September 2007 to March 2008. METHODOLOGY:
      The affluent socioeconomic group was identified by the monthly income of the
      parents (average>Rs.15,000 per month, $246); school fees of child
      (average>Rs.1,500 per month, $25) and household items such as computer,
      refrigerator, washing machine, television, car etc. A total of 652 healthy
      immunized children with no history of chronic infection, inducted through
      multistage stratified sampling were divided into groups A, B, and C by ages of 6
      9, 10-13, and 14-17 years respectively. Height, weight and 24 hours diet recall
      was obtained. Centre for Disease Control and prevention (CDC), clinical charts
      with 5th and 95 percentile for standard height and weight were used. Food records
      subjected to USDA food exchange list were used. Forms were used as inputs to
      generate tables for Statistical Package for social sciences -SPSS, Window 13.0.
      RESULTS: In girls calories and food intake in group A and B of Quetta was lower
      (p<.005) vs. other cities. No significant difference was seen in group C. Fat
      intake was the same in the girls of all 3 groups. In boys caloric carbohydrates
      and protein intake of group A of Quetta vs. groups B and C was significant by
      different National Centre for Health Statistics (NCHS) height and weight in
      groups A and B were at the 50-90 centile and at 25-50 in group C, centile. BMI
      (kg/m2) in girls and boys of group A were not different. BMI was highest in group
      B girls (mean 22+/-5) and group C boys (25+/-4) of Quetta. CONCLUSION: Children
      of affluent schools of Karachi compared to Quetta are taking more junk food but
      their consumption of protein is lowered and of a poor quality. Overall fat is
      below normal recommended standards. However, minimum fat intake was seen in
      school children of Quetta when compared with Karachi and Lahore. Carbohydrate
      consumption was adequate. BMI was highest in boys of Quetta than Lahore and
      Karachi. Majority of children on NCHS centile charts plotted between the 50th
      90th centiles.

PMID- 20141685
TI  - Accuracy of thallium scintigraphy versus coronary angiography for coronary artery
      disease in diabetics.
AB  - OBJECTIVE: To determine the sensitivity and specificity of thallium scintigraphy
      in detection of coronary artery disease in diabetic patients. STUDY DESIGN: Cross
      sectional validation study. PLACE AND DURATION OF STUDY: The study was carried
      out from July to December 2007 in the Cardiology Department of the Pakistan
      Institute of Medical Sciences, Islamabad. METHODOLOGY: A total of 60 diabetic
      patients suspected of having coronary artery disease were studied. Systematic
      probability sampling technique was used during their selection. All the patients
      underwent thallium scintigraphy followed by coronary angiography, which was used
      as gold standard test. RESULTS: Out of 60 patients, 44 had positive thallium
      scintigraphy and 16 were negative. Likewise, 46 had positive angiography and 14
      were negative. Out of 46 patients with positive angiography, thallium
      scintigraphy was positive in 41 subjects (sensitivity 89%) and false negative in
      only 5 of the 46 patients. Out of 14 patients with negative angiography, 11
      patients had a negative thallium scintigraphy (specificity 79%) and the remaining
      3 had a positive thallium scintigraphy. This gives thallium scintigraphy a
      positive predictive value of 93% and a negative predictive value of 69% when
      compared with angiography. CONCLUSION: Thallium scintigraphy is a useful modality
      in the detection of coronary artery disease in diabetic patients.

PMID- 20141687
TI  - Vertical facial and dental arch dimensional changes in extraction vs. non
      extraction orthodontic treatment.
AB  - OBJECTIVE: To compare the vertical facial and dental arch dimensional changes
      occurring with extraction and nonextraction orthodontic treatments. STUDY DESIGN:
      Cross-sectional comparative study. PLACE AND DURATION OF STUDY: The Aga Khan
      University Hospital, Karachi during the period 2003 to 2005. METHODOLOGY: Data
      were collected using records of patients who visited the study setting during the
      study period. Pre- and post-treatment lateral cephalographs and study casts of 81
      orthodontic patients (41=non-extraction and 40=premolar extractions) were taken.
      Variables used for evaluating vertical dimension were Frankfort mandibular plane
      angle (FMA), facial height (N-Me), facial height ratio (N-ANS/ANS-Me), soft
      tissue facial height (G' to Me'), soft tissue facial height ratio (G'-Sn'/zn'
      Me'), upper first molar to palatal plane and lower first molar to mandibular
      plane distance, posterior facial height to anterior facial height ratio (PFH/AFH)
      and Y-axis. Intercanine, interpremolar and intermolar widths and arch depths were
      also measured. To evaluate the pre-treatment and posttreatment comparison within
      each group, paired t-tests were used. For pre- and posttreatment comparisons
      between the extraction and non-extraction groups, independent sample t-tests were
      used. RESULTS: The mean age was 15.8+/-1.5 years for non-extraction and 15.4+/
      1.2 years for the extraction group. There was no significant difference in the
      vertical dimensional changes between extraction and non-extraction treatments as
      it increased in both groups. When comparing posttreatment arch dimensions, there
      was an increase in the maxillary intermolar width in the non-extraction group
      while the intermolar widths and arch depths decreased in the extraction group in
      both arches. CONCLUSION: Vertical dimensional changes showed no significant
      difference between extraction and non-extraction groups. Intermolar widths and
      arch depths decreased in both arches in the extraction group while the maxillary
      intermolar width increased in the non-extraction group.

PMID- 20141688
TI  - A Doppler-based evaluation of peripheral lower limb arterial insufficiency in
      diabetes mellitus.
AB  - OBJECTIVE: To determine the frequency, level and flow patterns of lower limb
      arterial insufficiency in diabetic patients on Doppler ultrasound study. STUDY
      DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Radiology Department,
      Civil Hospital, Karachi, from February 2007 to September 2008. METHODOLOGY: One
      hundred adult diabetic patients with suspected peripheral vascular insufficiency
      irrespective of gender were included. Demographic data, presenting complaints,
      treatment history, and level of HbA1c were recorded. Doppler evaluated arterial
      status and ankle brachial index (ABI) were recorded on proforma. Statical
      analysis were done on SPSS version 12. RESULTS: The mean HbA1c was 8.4+/-1.4
      gm/dl, a majority of 77% having a controlled level of <10mg/dl. Arterial
      insufficiency on Doppler ultrasound was documented in 62% (p=0.016) and the
      dorsalis paedis artery was the predominant site of stenosis (24%). Spectral
      broadening and biphasic flow were salient features. The mean value of resistive
      index in stenotic cases was 0.563+/-0.16 with a mean velocity difference of
      0.37+/-0.29 m/s (p<0.001) at the site of stenosis. CONCLUSION: Peripheral
      vascular insufficiency was a significant finding in patients having diabetes for
      an average of 9.8 years, even in the presence of controlled HbA1c. The dorsalis
      paedis was the commonest site of involvement. The insufficiency was moderate with
      a biphasic flow pattern in a majority of cases. Difference in resistive index and
      flow velocities at and above the site of stenosis provided an important clue to
      the diagnosis of level of stenosis that helps in planning limb salvage
      management.

PMID- 20141689
TI  - Gender difference and relationship of insulin resistance with microalbuminuria
      type-2 diabetes.
AB  - OBJECTIVE: To determine the relationship of insulin resistance with
      microalbuminuria in patients of type-2 Diabetes mellitus and observe gender
      difference if any. STUDY DESIGN: A cross-sectional study. PLACE AND DURATION OF
      STUDY: Diabetes Clinic of Combined Military Hospital, Malir Cantt, from April to
      August 2007. METHODOLOGY: One hundred and fifty five patients of type-2 Diabetes
      mellitus were included in the study who had either microalbuminuria or
      normoalbuminuria. Body mass index, waist circumference and blood pressure were
      recorded. Fasting venous blood sample was collected for plasma glucose (FPG),
      serum insulin, total and HDL cholesterol, triglycerides, creatinine and HbA1c.
      Urine albumin excretion was determined using urine albumin to creatinine ratio.
      Insulin resistance was calculated from fasting plasma glucose and serum insulin
      levels, using homeostatic model assessment of insulin resistance (HOMA-IR).
      Correlation and association testing was carried out with significance at p<0.05.
      RESULTS: Microalbuminuria was found to be significantly correlated with HOMA-IR
      (r=0.33, p<0.001), serum insulin (r=0.28, p=<0.001), body mass index (r=0.18,
      p=0.02) and waist circumference (r=0.21, p=0.008). This correlation was more
      significant in women (n=85, r=0.48, p=<0.0001) as compared to men (n=70, r=0.14,
      p=0.12). The correlation between HOMA-IR and urine albumin excretion remained
      highly significant (p=0.001) after controlling for gender, age, duration of
      diabetes, waist circumference, hypertension, triglycerides and HbA1c. CONCLUSION:
      Urinary albumin excretion in patients of type-2 diabetes is strongly associated
      with insulin resistance and related cardiovascular risk factors. This association
      appears to be stronger in women than the men, in our population.

PMID- 20141690
TI  - Tympanic temperature comparison with oral mercury thermometer readings in an OPD
      setting.
AB  - OBJECTIVE: To observe and compare the Tympanic Temperature (TT) readings with the
      Oral Mercury Thermometer (OMT) in an OPD setting. STUDY DESIGN: Observational
      comparative study. PLACE AND DURATION OF STUDY: The Outpatient Department, Shifa
      International Hospital, Islamabad, from June to September 2008. METHODOLOGY: By
      consecutive sampling, 2000 OPD patients were included in the study. Both tympanic
      membrane and oral cavity temperatures were recorded in each patient. Patients
      were grouped into four age classes i.e. 5-16, 17-40, 41-60 and above 60 years.
      Taking the oral temperature as a standard, tympanic temperature recordings were
      analyzed in each age group for afebrile and febrile temperature ranges. An intra
      class Pearson's correlation coefficient (r) was calculated for closeness of
      correlation of TT with OMT in each group. RESULTS: Mean age of the sample was
      31.84+/-19.42 years. Mean temperature reading from the OMT was 36.732+/-0.66
      degrees C, while the mean TT reading was 36.575+/-0.71 degrees C. Overall
      correlation between OMT and TT readings was 0.871 (p<0.001); higher correlation
      was found in children as compared to adults. In the febrile range, a strongly
      positive correlation of TT with OMT in the 5-16 years age group (r=0.945) was
      seen. A poor correlation of TT with OMT was noted for 41-60 and 60 plus groups
      (r=0.394 and 0.342 respectively). TT was found to have very high specificities in
      all age groups; highest of 100 in 17-40 years age group. The sensitivities were
      generally low, the lowest being 33.33 in 60 plus age group. CONCLUSION: TT
      measurement is a quick method for temperature recording in a busy OPD. However,
      it is reliable mainly for a younger population.

PMID- 20141691
TI  - Modified midline abdominal wound closure technique in complicated/high risk
      laparotomies.
AB  - OBJECTIVE: To assess the local wound complications in complicated/ high risk
      laparotomies in terms of wound dehiscence and incisional hernia formation with a
      modified technique of midline abdominal wound closure. STUDY DESIGN: Quasi
      experimental study. PLACE AND DURATION OF STUDY: Department of General Surgery,
      Combined Military Hospital, Bahawal Nagar Cantonment, May 2006 to June 2008.
      METHODOLOGY: Cases of complicated/high risk abdominal conditions, which required
      laparotomy, were included in the study. A modified midline abdominal wound
      closure technique was used. Interrupted Smead-Jones sutures with prolene, a non
      absorbable suture material for closure of linea alba was combined with mass
      closure involving all the layers (also with prolene) and drains were placed.
      Patients were followed-up for 3-23 months. The postoperative wound dehiscence and
      incisional hernia formation were noted. Other local wound complications were also
      recorded. RESULTS: Out of the 36 patients undergoing this surgical technique, 20
      (55.55%) had inflammatory/intra-abdominal sepsis, 8 (22.22%) had trauma, 7
      (19.44%) had neoplasia and 1 (2.77%) had vascular aetiology. Only 1 (2.77%) had
      partial wound dehiscence and 1 (2.77%) developed incisional hernia. Wound
      infection was noted in 12 (33.33%) cases; 4 (11.11%) experienced pain over the
      subcutaneous palpable knots and 3 (8.33%) developed sinus due to the knots. The
      average follow-up period was 12.47+7.17 months. CONCLUSION: Patients with
      extensive widespread generalized peritonitis and metastatic abdominal tumours
      need special attention regarding wound closure. This modified technique of
      midline abdominal wound closure is associated with low incidence of wound
      dehiscence and incisional hernia formation.

PMID- 20141692
TI  - Comparison of outcome in different types of stroke due to cerebral ischemia.
AB  - OBJECTIVE: To compare the outcome in different types of stroke according to
      cerebral ischemic region. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF
      STUDY: Medical Unit-I (Ward 5), Jinnah Postgraduate Medical Centre, from June
      2006 to April 2007. METHODOLOGY: A total of one hundred and forty seven patients
      of first ever cerebral infarcts admitted through emergency and medical OPD were
      included in the study and diagnosed on the basis of clinical findings and scan of
      brain. Detailed history and relevant examination was done. Causes of death during
      hospital stay were assessed. Discharged patients were followed-up in medical OPD
      and progress was monitored by modified Rankin scale at 1,3 and 6 months
      poststroke. RESULTS: One hundred and forty seven patients were studied. Their
      average age was 56.47+/-15.8 years. There were 80 (54.4%) males and 67 (45.6%)
      females. The stroke syndromes included partial anterior circulation stroke in 43
      (29.25%), posterior circulation stroke in 30 (20.41%), total anterior circulation
      stroke (TACS) in 36 (24.49%) and lacunar stroke in 38 (25.85%). During their
      hospital stay, 45 (30.6%) patients expired and 102 (69.3%) were discharged.The
      total mortality rate was 36.05% at one month, 40.1% at third month and 43.5% at
      sixth month poststroke. Mortality was significantly high in patients with TACS (n
      26, 72.2%, p-0.0001), Furthermore, at the time of incidence, 27.8%, 19.7% and
      14.2% cases respectively were functionally dependent. Twenty five (65.7%)
      patients of lacunar stroke were independent (p=0.002) at the end of the sixth
      month poststroke. CONCLUSION: TACS had the worst outcome with the highest number
      of mortalities, whereas lacunar stroke had a better outcome, i.e. a majority of
      the patients were functionally independent by the end of 6 months.

PMID- 20141693
TI  - Use of a pedicled flap for reconstruction of extensive soft tissue defects around
      elbow.
AB  - OBJECTIVE: To determine the reliability of pedicled latissimus dorsi flap for
      reconstruction of extensive defects around the elbow in terms of flap survival
      and coverage of exposed bones, vessels or nerves. STUDY DESIGN: Case series.
      PLACE AND DURATION OF STUDY: Department of Plastic and Reconstructive Surgery at
      Shaikh Zayed Hospital, from February 2003 to January 2008. METHODOLOGY: Patients
      with extensive traumatic wounds around the elbow and wounds secondary to release
      of postburn elbow contracture were included. Patients above 60 years of age with
      previous history of myocardial infarct, heart failure, chronic obstructive
      pulmonary disease or insulin dependent diabetes were excluded. Pedicled
      latissimus dorsi flap was used for defect reconstruction. Overall flap survival
      and postoperative complications were the outcome measures. RESULTS: There were 28
      patients, including 20 males and 8 females, age ranging from 17 to 60 years.
      Evaluation of the defect considering extent of tissue loss, depth of the defect
      and exposed vital structure was done. Myocutaneous flap was used in 4 (14%)
      patients. Muscle only flap was used in 24 patients (86%). Twenty five (90%) flaps
      survived completely and 3 (10%) had partial loss. Other minor complications were
      partial graft loss seen in 3 (10%) patients and wound infection seen in 2 (7%)
      patient. There was no considerable morbidity at donor site and all patients had
      satisfactory healing. CONCLUSION: Pedicled latissimus dorsi flap is a reliable
      and safe option for resurfacing extensive soft tissue defects of arm, elbow and
      forearm.

PMID- 20141694
TI  - Transurethral incision of prostate (TUIP) for minimally enlarged prostates.
AB  - OBJECTIVE: To compare the efficacy of Transurethral Incision of Prostate (TUIP)
      with Transurethral Resection of Prostate (TURP), in terms of improvement in peak
      flow rate (Q-Max) and number of complications. STUDY DESIGN: It was an
      interventional, quasi-experimental study. PLACE AND DURATION OF STUDY: This study
      was conducted at the Armed Forces Institute of Urology (AFIU), Rawalpindi, from
      November 2006 to December 2007. METHODOLOGY: A total of 60 patients were inducted
      in the study with thirty patients in each group undergoing TUIP (Group A) and
      TURP (Group B). Patients of any age with prostate less than 35 grams needing
      surgical interventions were included in the study. Patients with recurrent
      disease, multiple co-morbid conditions, higher center dysfunctions, neurogenic
      bladder and associated strictures were excluded. In TUIP, a single median
      incision was made at 6 'O clock position, starting from interureteric ridge upto
      verumontanum, going upto prostatic capsule. In group B, standard TURP was done.
      All the cases were operated by the same consultant under spinal anaesthesia.
      Follow up was done at the end of the 1st week and 1st, 3rd and 6th months.
      RESULTS: Mean operative time was shorter (17.01+/-1.97 minutes) in group A as
      compared to group B (27.06+/-23.06 minutes, p<0.05). There was no statistically
      significant difference between the two groups regarding peak flow. Complications
      were less in group A (08) and more in group B (n=28, <0.05). CONCLUSION: TUIP and
      TURP were equal in terms of improvement in flow rate, but operative time was
      shorter in TUIP with less post operative complications. So, TUIP is a better
      choice in prostates weighing less than 35 grams.

PMID- 20141695
TI  - Follicular dendritic cell sarcoma of tonsil.
AB  - Follicular dendritic cell sarcoma is a very rare entity. So far only 12 cases
      have been reported world wide with involvement of tonsil. We present a new case
      of follicular dendritic cell sarcoma of the tonsil in a 52 years old woman with
      no evidence of neck node involvement. She had undergone diagnostic tonsillectomy
      due to unilateral tonsillar enlargement. The final diagnosis after histological
      review and immunohistochemical stains was follicular dendritic cell sarcoma. Bone
      scan showed no metastasis. One year follow-up after postoperative chemotherapy
      showed no evidence of local or regional recurrence. Follicular dendritic cell
      sarcoma is a rare and underdiagnosed neoplasm. It should be included in the
      differential diagnosis of any tonsillar mass in adults. Follicular dendritic cell
      markers such as SR-100, CD21 and/or CD35 are essential for the diagnosis.

PMID- 20141696
TI  - Hepatic vein and inferior vena caval thrombus extending into the right atrium: a
      rare complication of amoebic liver abscess.
AB  - Amoebic liver abscess is an endemic in developing countries but few cases of
      associated vascular complications have been reported. The authors report a very
      rare vascular complication of hepatic veins and inferior vena caval (IVC)
      thrombosis extending into the right atrium in a young male with large amoebic
      liver abscess. Optimal result was achieved with early diagnosis on CT scan,
      percutaneous drainage of abscess, intravenous metronidazole, peri-operative
      anticoagulation, sternotomy and thrombectomy.

PMID- 20141697
TI  - Abdominal wall endometriosis.
AB  - Abdominal wall endometriosis is a rare condition, which usually develops in a
      surgical scar of abdominal hysterectomy or Caesarean section. A 38-year-old lady
      presented in the surgical out patient department complaining of painful swelling
      in the lower abdomen, at the left edge of the scar of caesarean section.
      Computerized tomographic (CT) scanning of the pelvis with contrast revealed an
      enhancing mass in the abdominal wall extending from the skin to the muscle layer.
      A diagnosis of a tumour or an inflammatory mass was suggested and fine needle
      aspiration cytology (FNAC) of the lesion was advised to ascertain the nature of
      the lesion. The mass was removed completely and histopathology of the surgical
      specimen revealed endometriosis.

PMID- 20141699
TI  - Rehabilitation of nose using silicone based maxillofacial prosthesis.
AB  - Surgical reconstruction of large facial defects is not possible at times due to
      extensive loss of tissue that cannot be corrected by surgery alone. In these
      cases, prosthetic restoration of lost facial tissue can be done using
      maxillofacial prosthetics. Introduction of new material which gives life-like
      appearance to such prosthetic restorations e.g. silicone and poly ether rubbers
      and use of implants to retain these prostheses have given a new dimension to
      rehabilitation of such patients. This report presents a case of prosthetic
      rehabilitation of the nasal component of the face secondary to nasal
      leishmaniasis, using precision attachment retained maxillofacial prosthesis.

PMID- 20141698
TI  - Posttransplantation lymphoproliferative disorder with skin involvement.
AB  - Posttransplantation lymphoproliferative disorders (PTLD) are lymphoid
      proliferations or lymphomas that develop as a result of immunosuppression in
      recipients of solid organs and bone marrow allografts. The disorder is seen in 1
      2% of renal transplant recipients with a variable time period of presentation and
      is usually seen within the first year following transplantation. We report a case
      of B-cell lymphoma (PTLD WHO class-3) presenting with skin involvement in a
      patient of renal transplantation, 8 years after receiving the transplant.

PMID- 20141700
TI  - The pattern and outcome of adult tetanus at a sub-urban tertiary hospital in
      Nigeria.
AB  - Though tetanus is a major cause of preventable morbidity and mortality in
      Nigeria, there is a paucity of data on the pattern and outcome of the disease
      among the sub-urban and rural populations. This retrospective study of adult
      tetanus at a suburban tertiary hospital in Nigeria reports a high case fatality
      rate of 57.1% in 35 patients with a mean age of 33.0+/-14.8 years. Severity of
      disease (p=0.02), presence of complications (p=0.001) and length of hospital stay
      (p<0.001) were significantly associated with fatality. Preventive measures for
      control of tetanus should be extended to the inaccessible suburban and rural
      areas of Nigeria.

PMID- 20141702
TI  - Diagnosis and treatment of bipolar disorder in young patients.
AB  - Untreated early-onset bipolar disorder is associated with higher rates of rapid
      cycling, more comorbidity, and more severe mania and depression than adult-onset
      bipolar disorder. Correctly diagnosing bipolar disorder early in its course can
      prevent exposing a young patient to treatments that may exacerbate or advance the
      progression of the disorder. Appropriate pharmacologic and psychosocial
      interventions are necessary in the acute treatment of pediatric bipolar disorder.

PMID- 20141703
TI  - Treating major depression: antidepressant algorithms.
AB  - Clinicians currently have a large number of pharmaceutical options available for
      the treatment of depression, yet not one of these treatments is associated with
      especially high remission rates. Further complicating the treatment of depression
      is the fact that the more failed treatment trials a patient undergoes, the lower
      the odds that remission will be achieved. Therefore, choosing the drug that will
      be most effective for a particular patient early in the treatment process is
      essential. Antidepressant treatment algorithms are helpful in this regard.

PMID- 20141704
TI  - Differential diagnoses and assessment of depression in elderly patients.
AB  - Depression in the elderly contributes to decreased quality of life and increased
      mortality from both suicide and medical illnesses, yet it remains underdiagnosed
      and undertreated in these patients. Physicians should be aware of the varying
      presentations of depression in older adults and differentiate late-life
      depression from other psychiatric diagnoses. Thorough medical and cognitive
      assessments are necessary to determine whether late-life depression is due to
      underlying medical causes and neurologic diagnoses such as Alzheimer's disease or
      dementia. Depression rating scales, cognitive screening instruments, and
      structural and functional neuroimaging studies may be implemented as the
      situation requires. Greater recognition and more aggressive treatment of
      depression in older patients are needed.

PMID- 20141705
TI  - Long-term effects of preventive cognitive therapy in recurrent depression: a 5.5
      year follow-up study.
AB  - OBJECTIVE: Major depressive disorder (MDD) was projected to rank second on a list
      of 15 major diseases in terms of burden in 2030. A crucial part of the treatment
      of depression is the prevention of relapse/recurrence in high-risk groups, ie,
      recurrently depressed patients. The long-term preventive effects of group
      cognitive therapy (CT) in preventing relapse/recurrence in recurrent depression
      are not known. This article reports on the long-term (5.5-year) outcome of a
      randomized controlled trial to prevent relapse/recurrence in patients with
      recurrent depression. We specifically evaluated the long-term effects of CT in
      relation to the number of previous episodes experienced. METHOD: From February
      through September 2000, patients with recurrent depression (DSM-IV-diagnosed) who
      were in remission (N = 172) were recruited from primary and specialty care
      facilities. They were randomly assigned to treatment as usual (TAU) versus TAU
      augmented with brief group CT. The primary outcome measure was time to
      relapse/recurrence, which was assessed over 5.5 years. RESULTS: Over 5.5 years,
      augmenting TAU with CT resulted in a significant protective effect (P = .003),
      which intensified with the number of previous depressive episodes experienced.
      For patients with 4 or more previous episodes (52% of the sample), CT
      significantly reduced cumulative relapse/recurrence from 95% to 75% (medium
      effect size). CONCLUSIONS: Our findings indicate that brief CT, started after
      remission from a depressive episode on diverse types of treatment in patients
      with multiple prior episodes, has long-term preventive effects for at least 5.5
      years. Implementation of brief relapse prevention CT should be considered in the
      continued care of patients with recurrent depression. TRIAL REGISTRATION: ccmo
      online.nl Identifier: NTR454.

PMID- 20141706
TI  - Short-term effects of lisdexamfetamine dimesylate on cardiovascular parameters in
      a 4-week clinical trial in adults with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To evaluate the short-term impact of lisdexamfetamine dimesylate on
      cardiovascular parameters in adults with attention-deficit/hyperactivity disorder
      (ADHD). METHOD: Medically healthy adults (18-55 years of age) with DSM-IV-TR
      defined ADHD were randomly assigned to placebo or 30, 50, or 70 mg/d of
      lisdexamfetamine dimesylate for 4 weeks between May and November 2006.
      Electrocardiograms, systolic and diastolic blood pressure, and pulse were
      assessed pretreatment and weekly thereafter. RESULTS: There were no significant
      differences for mean systolic or diastolic blood pressure in any lisdexamfetamine
      dimesylate dose group versus placebo. Changes in pulse from baseline to endpoint
      were 0.0, 2.8, 4.2, and 5.2 bpm in the placebo and lisdexamfetamine dimesylate
      30, 50, and 70 mg/d groups, respectively (P < .05, all lisdexamfetamine
      dimesylate groups vs placebo). Post hoc pulse outliers (pulse > or = 100 bpm; any
      1 event) ranged from 3.3% to 8.5% of subjects in the lisdexamfetamine dimesylate
      groups, and no subjects in the placebo group were pulse outliers (P < .05 for
      lisdexamfetamine dimesylate 50 mg vs placebo only). There were no clinically
      meaningful electrocardiogram abnormalities. Overall, 8.3% (35/420; safety
      population) of subjects had treatment-emergent cardiovascular adverse events, and
      1.7% (7/420) withdrew from the study because of cardiovascular complaints.
      Cardiovascular adverse events with lisdexamfetamine dimesylate in these medically
      healthy adults were generally mild to moderate in severity. CONCLUSIONS:
      Lisdexamfetamine dimesylate had limited short-term effects on heart rate, blood
      pressure, and electrocardiogram parameters that were of minimal clinical concern.
      These findings support the relative safety of lisdexamfetamine dimesylate.
      However, considering the potential of outliers, it is advisable to monitor
      cardiovascular parameters in stimulant-treated patients. Interpretation of these
      findings is limited to patients with no preexisting cardiac conditions who are
      taking their medication as prescribed. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00334880.

PMID- 20141707
TI  - Women's mental health: hot topics and clinical implications.

PMID- 20141708
TI  - Interactions between tamoxifen and antidepressants via cytochrome P450 2D6.
AB  - OBJECTIVE: Women taking tamoxifen for the treatment or prevention of recurrence
      of breast cancer are likely to take antidepressants either for a psychiatric
      disorder or for hot flashes. Recent evidence suggested that some antidepressants
      inhibit the metabolism of tamoxifen to its more active metabolites by the
      cytochrome P450 2D6 (CYP2D6) enzyme, thereby decreasing the anticancer effect.
      This article reviews the literature on the interactions between newer
      antidepressants and tamoxifen via CYP2D6 and offers treatment recommendations.
      DATA SOURCES: A literature search of clinical and nonclinical studies published
      prior to September 2008 was conducted on PubMed. We performed 3 different
      searches combining the terms tamoxifen and SSRIs; tamoxifen and CYP2D6
      inhibitors; and antidepressant and breast cancer recurrence. A fourth search with
      CYP2D6 inhibition and the generic names of individual antidepressants was carried
      out. STUDY SELECTION: Seven clinical research articles were selected. Nonclinical
      research articles about antidepressants were included if they mentioned in vitro
      or in vivo inhibition of CYP2D6. DATA SYNTHESIS: There is consistent evidence
      that paroxetine and fluoxetine have a large effect on the metabolism of tamoxifen
      and should not be used. Indirect evidence indicates that bupropion may also have
      a large effect on the metabolism of tamoxifen. Venlafaxine has little or no
      effect on the metabolism of tamoxifen and may be considered the safest choice of
      antidepressants. Desvenlafaxine is not metabolized by the P450 system and may
      consequently be another option. Mirtazapine has not been extensively studied, but
      existing research suggests minimal effect on CYP2D6. The remaining commonly
      prescribed antidepressants have mild to moderate degrees of CYP2D6 inhibition.
      CONCLUSIONS: Clinicians treating patients with breast cancer should review the
      prescription profiles of their patients to evaluate the need for treatment
      modification. There are safe options for the treatment of depression and
      clinicians and patients should bear in mind the health risks of untreated
      depressive states.

PMID- 20141709
TI  - Distressing sexual problems in United States women revisited: prevalence after
      accounting for depression.
AB  - OBJECTIVE: With data from the population-based Prevalence of Female Sexual
      Problems Associated with Distress and Determinants of Treatment Seeking (PRESIDE)
      study, which has previously estimated the prevalence of sexual problems and
      sexually related personal distress in United States women, the prevalence of
      sexual disorders of desire, arousal, and orgasm was re-estimated, taking
      concurrent depression into consideration. METHOD: Current depression was defined
      in 3 ways as (1) self-reported symptoms alone, (2) antidepressant medication use
      alone, or (3) symptoms and/or antidepressant use. The unadjusted population
      prevalence for each distressing sexual problem in the 31,581 respondents was
      calculated first irrespective of concurrent depression and then in women without
      concurrent depression, thus determining the size of the population with both
      conditions present. RESULTS: The unadjusted population-based prevalence of desire
      disorder was 10.0% and was reduced to 6.3% for those without concurrent
      depression, leading to an estimate of 3.7% for those with both conditions
      present. The same pattern was observed for arousal and orgasm disorders, although
      overall prevalence estimates were lower. CONCLUSIONS: Our findings indicate that
      about 40% of those with a sexual disorder of desire, arousal, or orgasm have
      concurrent depression, As this study was cross-sectional, causality versus
      comorbidity cannot be determined. However, our findings stress the importance of
      evaluating depression along with sexual problems in routine clinical practice and
      epidemiology research.

PMID- 20141711
TI  - Time trends in age at onset of anorexia nervosa and bulimia nervosa.
AB  - OBJECTIVE: This study aims to explore the time trends in age at onset of anorexia
      nervosa and bulimia nervosa. METHOD: The sample was composed of 1,666 anorexia
      nervosa subjects and 793 bulimia nervosa subjects (according to DSM-IV criteria)
      without previous anorexia nervosa consecutively referred to our outpatient unit
      in the period between 1985 and 2008. Time trends in illness onset were analyzed
      according to the year of birth of subjects. RESULTS: In both anorexia nervosa and
      bulimia nervosa, age at onset showed a significant decrease according to year of
      birth. A regression model showed a significant independent effect of
      socioeconomic status, age at menarche, and number of siblings in predicting age
      at onset lower than 16 years. CONCLUSION: Age at onset of anorexia nervosa and
      bulimia nervosa is decreasing in younger generations. The implications of our
      findings in terms of long-term outcome remain to be understood. Biologic and
      sociocultural factors explaining this phenomenon need to be explored in future
      studies.

PMID- 20141710
TI  - Leisure-time physical activity in pregnancy and risk of postpartum depression: a
      prospective study in a large national birth cohort.
AB  - OBJECTIVE: To explore the association between physical activity during pregnancy
      and postpartum depression (PPD) in a large, prospective cohort. METHOD: Exposure
      information from the Danish National Birth Cohort, a large, prospective cohort
      with information on more than 100,000 pregnancies (1996-2002), was linked to the
      Danish Psychiatric Central Register and the Danish Register for Medicinal Product
      Statistics for data on clinically identified cases of depression up to 1 year
      postpartum. A total of 70,866 women from the Danish National Birth Cohort were
      included in the analyses. Duration, frequency, and type of physical activity were
      assessed by a telephone interview at approximately week 12 of gestation.
      Admission to hospital due to depression (PPD-admission) and prescription of an
      antidepressant (PPD-prescription) were treated as separate outcomes. RESULTS:
      Through linkage to national registers, we identified 157 cases of PPD-admission
      and 1,305 cases of PPD-prescription. Women engaging in vigorous physical activity
      during pregnancy had a lower risk of PPD-prescription compared to women who were
      not physically active (adjusted odds ratio, 0.81; 95% CI, 0.66-0.99). No
      association was observed between physical activity and PPD-admission; but, in
      women who were underweight prior to pregnancy, physical activity was associated
      with increased risk of PPD-admission. CONCLUSIONS: Our data are compatible with a
      protective effect of vigorous physical activity, but not for other measures of
      physical activity, against postpartum depression requiring antidepressant
      therapy. No protective effect could be detected on PPD leading to
      hospitalization.

PMID- 20141712
TI  - Reconceptualizing medication management: implications for training and clinical
      practice.

PMID- 20141713
TI  - A novel mutation of the arylsulfatase A gene in late-onset metachromatic
      leukodystrophy.

PMID- 20141714
TI  - Sudden cardiac death in users of second-generation antipsychotics.

PMID- 20141716
TI  - Does depressive state influence reported attachment status?

PMID- 20141717
TI  - The benzodiazepine stigma persists.

PMID- 20141719
TI  - Treating dyslipidemia in the high-risk patient.
AB  - Clinical trials demonstrate that cardiovascular event rates diminish as low
      density lipoprotein (LDL)-cholesterol and apolipoprotein B-containing particles
      are lowered with statin treatment. The relationship between LDL-cholesterol and
      cardiovascular events seems to be linear, with no lowest threshold. While LDL
      cholesterol remains the primary target for coronary heart disease prevention, non
      HDL-cholesterol is an important secondary target in patients with mixed
      dyslipidemia.

PMID- 20141720
TI  - Chlamydia screening: how we can better serve patients.

PMID- 20141721
TI  - Spotting-and treating-PTSD in primary care.

PMID- 20141722
TI  - A new glucose monitoring option.

PMID- 20141723
TI  - The skin disorders of pregnancy: a family physician's guide.

PMID- 20141724
TI  - Detecting the other reflux disease.

PMID- 20141725
TI  - Start a statin prior to vascular surgery.

PMID- 20141726
TI  - Surprising finding on colonoscopy.
AB  - A 48-year-old man went to his primary care physician for his annual physical. He
      told his physician that for the past few years, he had intermittent, painless
      rectal bleeding consisting of small amounts of blood on the toilet paper after
      defecation. He also mentioned that he often spontaneously awoke, very early in
      the morning. His past medical history was unremarkable. The patient was born in
      Cuba but had lived in the United States for more than 30 years. He was divorced,
      lived alone, and had no children. He had traveled to Latin America-including
      Mexico, Brazil, and Cuba-off and on over the past 10 years. His last trip was
      approximately 2 years ago. His physical exam was unremarkable. Rectal examination
      revealed no masses or external hemorrhoids; stool was brown and Hemoccult
      negative. Labs were remarkable for eosinophilia ranging from 10% to 24% over the
      past several years (the white blood cell count ranged from 5200 to 5900/mcL). A
      subsequent colonoscopy revealed many white, thin, motile organisms dispersed
      throughout the colon. The organisms were most densely populated in the cecum. Of
      note, the patient also had nonbleeding internal hemorrhoids. An aspiration of the
      organisms was obtained and sent to the microbiology lab for further evaluation.
      What is your diagnosis? How would you manage this condition?

PMID- 20141727
TI  - How accurate is an MRI at diagnosing injured knee ligaments?

PMID- 20141728
TI  - Do endovascular filters prevent PE as effectively as anticoagulants in patients
      with DVT?

PMID- 20141729
TI  - [Possibility and necessity of constructing new nanoformula systems of traditional
      Chinese medicine].
AB  - The past decade has witnessed the remarkable progress on nanotechnology and
      nanoherb. With the globally rapid development of nanotechnology, we are
      considering to construct new nanoformula systems of traditional Chinese medicine
      (TCM) by using porous materials, multilayered core-shell particles or
      nanoparticles containing various multifunctional parts. With the compatibility of
      sovereign, minister, assistant and courier in a formula, new nanoformula systems
      of TCM will have various advantages, such as containing multiple active species,
      controlled release, targeting function, and labeling and tracing capabilities.
      Using the latest breakthroughs of nanotechnology for the modern research of TCM
      will greatly help enhance the ability to investigate the principles of TCM, and
      to design, screen and utilize new nanoformula systems of TCM.

PMID- 20141730
TI  - [Study strategies for neurobiology mechanism of "kidney storing will and
      responding to fear"].
AB  - The theory of traditional Chinese medicine (TCM) deems that kidney essence is the
      material basis of formation, development and function of the brain and it
      maintains human being's psychomotility and behavior. Moreover, kidney essence is
      the material basis of emotional activity. The emotion theory in TCM deems that
      kidney stores will and responds to fear. The so called will in this theory refers
      to memory which includes three basic steps such as memorization, storage and
      recollection. Meanwhile, Western medicine considers stress as a kind of
      information that forms memory trace in central nervous system. Combining the TCM
      theory with the modern psychological theory on stress, and from the points of
      views of the emotion regulation, the formation, consolidation, extraction and
      extinction of fear memory, and the plasticity of amygdala-hippocampus-prefrontal
      cortex nervous pathway, as well as the results of pharmacological studies of
      prescriptions and herbs for invigorating the kidney, the authors explained in
      this article the pathological mechanisms of kidney deficiency due to attack of
      fear, and revealed the material basis, the action modes, and the neurobiological
      mechanisms of the kidney in controlling and regulating emotional activity.

PMID- 20141731
TI  - Relationship between gene expressions of aquaporin 3 and 4 and various degrees of
      spleen-stomach dampness-heat syndrome in chronic superficial gastritis.
AB  - OBJECTIVE: To explore the relationship between gene expressions of aquaporin
      (AQP) 3 and 4 and various degrees of spleen-stomach dampness-heat syndrome in
      chronic superficial gastritis (CSG). METHODS: Twenty-four CSG patients were
      divided into three groups according to the degrees of spleen-stomach dampness
      heat syndrome: mild, moderate and severe groups. There were 8 patients in each
      group, and another 8 healthy persons were selected as normal control. Samples of
      mucosa of upper stomach in the included patients and normal persons were
      collected by gastroscopy, and then were stored in liquid nitrogen. The gene
      expressions of AQP3 and AQP4 in gastric tissue were examined by fluorescence
      quantitative polymerase chain reaction. RESULTS: The gene expressions of AQP3 and
      AQP4 in the moderate and severe groups were higher than that in the mild group
      and normal group (P<0.05, P<0.01). The gene expression of AQP3 in the severe
      group was higher than that in the moderate group (P<0.05). CONCLUSION: The gene
      expressions of AQP3 and AQP4 in gastric mucosa are different in patients with
      various degrees of spleen-stomach dampness-heat syndrome of CSG. There is a
      relationship between expressions of AQP3 and AQP4 genes and the degrees of spleen
      stomach dampness-heat syndrome, and the gene expressions will increase with the
      aggravation of the dampness-heat syndrome.

PMID- 20141732
TI  - [Survival time of advanced gastric cancer patients treated with integrated
      traditional Chinese and Western medicine therapy].
AB  - BACKGROUND: Advanced gastric cancer has a low survival rate while traditional
      Chinese medicine (TCM) therapy has effects in inhibiting tumor growth,
      lengthening survival time and improving the quality of life. OBJECTIVE: To
      analyze the effects of integrated traditional Chinese and Western medicine
      therapy on the survival time and quality of life of advanced gastric cancer
      patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 95 advanced
      gastric cancer patients were enrolled and divided into comprehensive group (48
      cases) and control group (47 cases). The patients in the comprehensive group from
      the First Department of Oncology, Longhua Hospital, were treated with TCM therapy
      and chemotherapy based on the gastric cancer treatment guidelines made by the
      First Department of Oncology of Longhua Hospital, and the patients in the control
      group from Renji Hospital and Ruijin Hospital in Shanghai were treated with
      chemotherapy only. MAIN OUTCOME MEASURES: The survival time in the two groups
      were observed and compared. The Karnofsky score, body weight, the European
      Organization for Research and Treatment of Cancer Core Quality of Life
      Questionnaire (EORTC QLQ-C30) score, response rate and chemotherapy-related
      adverse events in the comprehensive group were observed. RESULTS: The estimated
      median survival time in the comprehensive group was 16.12 months, longer than
      9.64 months in the control group (P<0.05). The scores of function and symptom of
      EORTC QLQ-C30 in the comprehensive group decreased, while the overall health
      status increased, and the results indicated that the quality of life of the
      patients in the comprehensive group was improved. In the comprehensive group, the
      body weight after treatment was higher than that before treatment (P=0.037),
      while there was no difference in Karnofsky scores between that before and after
      treatment (P=0.061). All the patients in the comprehensive group were assessable.
      The complete response rate was 0, 3 cases had a partial response, 34 cases had
      stable disease, and 11 cases had disease progression. The overall response rate
      was 6.25% (3/48), and the disease control rate was 77.08% (37/48). No patient
      withdrew because of severe adverse events and there was no chemotherapy-related
      death. CONCLUSION: Integrated traditional Chinese and Western medicine can
      prolong the survival time and improve the quality of life of advanced gastric
      cancer patients, and enhance the comprehensive effects.

PMID- 20141733
TI  - [Development of patient-reported outcome scale for myasthenia gravis: a
      psychometric test].
AB  - OBJECTIVE: To investigate the scientificity of patient-reported outcome (PRO)
      scale for myasthenia gravis (MG), which was used to evaluate the clinical effects
      of traditional Chinese and Western medicine treatment on MG patients.
      Psychometric performance of the MG-PRO scale was also expected to be evaluated in
      this study. METHODS: A total of 100 MG patients and 100 healthy people were face
      to-face interviewed by well-trained investigators, and the data of MG-PRO scale
      were collected. The classical theory test (CTT) and item response theory (IRT)
      methods were used to analyze the psychometric performance such as validity,
      reliability, person separation index (PSI) and differential item functioning
      (DIF) in the MG-PRO scale. RESULTS: The results of CTT analysis showed that the
      split-half reliabilities of the MG-PRO scale and each dimension were greater than
      0.7. In the analysis of internal consistency of each dimension, the Cronbach's
      alpha was greater than 0.8. Each facet had greater correlation with its dimension
      than the other dimensions. Four principal components were extracted by
      exploratory factor analysis, which represented all dimensions of the scale, and
      the cumulative variance was 55.54%. The scores of each of the 8 facets between MG
      patients and healthy people were different (P<0.01). The results of IRT showed
      that the PSI of each model was greater than 0.8, and all items did not have
      uniform DIF and non-uniform DIF. CONCLUSION: The MG-PRO scale reflects the
      definition and connotation of quality of life and contains special issues of MG
      patients as well, and shows good reliability (split-half reliability, Cronbach's
      alpha), validity (content validity, construct validity, discriminate validity)
      from the results of CTT, and good psychometric performance from the results of
      IRT.

PMID- 20141734
TI  - [Scalp penetration acupuncture for insomnia: a randomized controlled trial].
AB  - BACKGROUND: Insomnia has become a threat to public health, and acupuncture has
      shown an advantage in treatment of insomnia with good efficacy and few side
      effects. OBJECTIVE: To observe the therapeutic effects of scalp penetration
      acupuncture for insomnia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A
      total of 70 insomnia cases meeting inclusion criteria from Department of
      Acupuncture and Moxibustion, General Hospital of People's Liberation Army were
      randomly divided into routine acupuncture group and scalp penetration acupuncture
      group. There were 32 cases in the scalp penetration acupuncture group, and 34
      cases in the routine acupuncture group, for four cases lost to follow-up. The
      insomnia patients were all treated for four weeks. MAIN OUTCOME MEASURES: The
      therapeutic effects, cumulative scores of Pittsburgh Sleep Quality Index (PSQI)
      and contents of sleep architecture were compared before and after treatment in
      the two groups. RESULTS: The total response rate of 90.6% in the scalp
      penetration acupuncture group was higher than 73.5% in the routine acupuncture
      group (P<0.05), and the improvements of PSQI cumulative scores in sleep quality,
      sleep time and sleep efficiency in the scalp penetration acupuncture group were
      superior to those in the routine acupuncture group (P<0.05, P<0.01). The total
      sleep time and deep sleep time of sleep architecture in the scalp penetration
      acupuncture group significantly increased as compared with those in the routine
      acupuncture group (P<0.01). CONCLUSION: The therapeutic effects of scalp
      penetration acupuncture are better than those of routine acupuncture, especially
      for improving sleep quality, sleep time and sleep efficiency.

PMID- 20141735
TI  - Panax notoginseng saponins protect rabbit bone marrow stromal cells from hydrogen
      peroxide-induced apoptosis.
AB  - OBJECTIVE: To investigate the effects of Panax notoginseng saponins (PNSs) on
      hydrogen peroxide-induced apoptosis in rabbit bone marrow stromal cells (BMSCs).
      METHODS: BMSCs were isolated from 2-month-old New Zealand rabbits and cultured
      with different doses of PNSs to determine the most effective dose of PNSs by 3
      (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and
      alkaline phosphatase (ALP) assay. The most effective dose of PNSs was used in
      subsequent experiments. Apoptosis of BMSCs was induced by hydrogen peroxide (100
      micromol/L). BMSCs in PNSs group were also pretreated with PNSs before hydrogen
      peroxide exposure. Reactive oxygen species (ROSs) levels were measured by using
      2',7'-dichlorodihydrofluorescein diacetate. Apoptosis rate of BMSCs was observed
      by flow cytometry after staining with Annexin V-fluorescein
      isothiocyanate/propidium iodide. The protein expression of Bax in BMSCs was
      analyzed by Western blotting. Activity of caspase-3 was measured by
      spectrofluorometry. RESULTS: The most effective dose of PNSs was 0.1g/L. PNSs at
      dose of 0.1g/L markedly reversed the augmentation of ROS level, decreased the
      apoptosis rate of, and the Bax expression and activity of caspase-3 in BMSCs
      treated with hydrogen peroxide (P<0.01). CONCLUSION: PNSs can protect cultured
      rabbit BMSCs from hydrogen peroxide-induced apoptosis by decreasing oxidative
      stress, Bax expression and caspase-3 activity.

PMID- 20141736
TI  - [Effects of Xiaotan Jieyu Recipe on behaviors of tumor-bearing rats with chronic
      mild stress and the mechanism].
AB  - OBJECTIVE: To investigate the effects of unpredictable chronic mild stress and
      Xiaotan Jieyu Recipe (XTJYR), a compound traditional Chinese herbal medicine, on
      the behaviors of Walker 256 tumor-bearing rats and to explore the mechanism.
      METHODS: Sixty Wistar rats were randomly divided into control group, stress
      group, tumor-bearing group, stress plus tumor-bearing group, fluoxetine group and
      XTJYR group. After treatment, sucrose solution consumption, score of ethology,
      body weight and serum levels of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) were detected, expressions of Bcl-2 and phosphorylated
      extracellular signal-regulated kinase 1/2 (p-ERK1/2) proteins in hippocampus were
      detected by Western blotting method, and expression of Bcl-2 mRNA was measured by
      polymerase chain reaction method. RESULTS: Sucrose solution consumption,
      behavioral scores and body weight of rats were decreased in the stress group and
      the tumor-bearing group as compared with the control group. There were
      significant differences in expressions of Bcl-2 mRNA and Bcl-2 and p-ERK1/2
      proteins in hippocampus and contents of serum TNF-alpha and IL-6 in the stress
      group and the tumor-bearing group as compared with those in the control group.
      XTJYR had the efficacy in improving behavioral scores of stress rats and tumor
      bearing rats, down-regulating the contents of serum TNF-alpha and IL-6 and
      increasing the expressions of proteins of Bcl-2 and p-ERK1/2. CONCLUSION: Tumor
      bearing rats are prone to behave depressively after exposure to chronic mild
      stress and XTJYR can improve the behavioral scores of the rats. The mechanisms of
      XTJYR may relate to regulating contents of serum TNF-alpha and increasing the
      protein expressions of Bcl-2 and p-ERK1/2.

PMID- 20141737
TI  - [Effects of astilbin on maturation and immunologic function of mouse bone marrow
      derived dendritic cells].
AB  - OBJECTIVE: To explore the effects of astilbin on the maturation and immunologic
      function of mouse bone marrow-derived dendritic cells (DCs). METHODS: Mouse bone
      marrow cells were cultured with recombinant mouse granulocyte-macrophage colony
      stimulating factor and interleukin-4 (IL-4) for 5 days to get immature DCs
      (imDCs), then the imDCs was cultured in the presence of 1 microg/mL
      lipopolysaccharide (LPS) or LPS (1 microg/mL) plus astilbin (25, 50, 100
      microg/mL) for 48 h. Then, the cells were harvested, and the apoptosis,
      immunophenotypes and antigen phagocytosis capability of imDCs in LPS, and low-,
      medium- and high-dose astilbin groups were analyzed by flow cytometry. Contents
      of p40 subunit of interleukin-12 (IL-12p40) in the supernatants were detected
      with enzyme-linked immunosorbent assay (ELISA). The stimulatory activity of the
      harvested cells on allogeneic T cells in mixed lymphocyte reactions (MLR) was
      tested by incorporation of 3H-thymidine, and the contents of IL-2, IL-4, IL-10
      and interferon-gamma (INF-gamma) in the supernatants of MLR were examined by
      ELISA. RESULTS: At the concentrations of 25 to 100 microg/mL, astilbin exhibited
      no toxicity on co-cultured DCs. Compared with the lipopolysaccharide, low-,
      medium- and high-dose astilbin could decrease the expression levels of major
      histocompatibility complex-Ia (MHC-Ia), CD40, CD80 and CD86 molecules in DCs. DCs
      in the low-, medium- and high-dose astilbin groups exhibited weaker capabilities
      for antigen phagocytosis and less contents of IL-12p40 in the supernatants than
      in the LPS group. Furthermore, low-, medium- and high-dose astilbin showed weak
      activities in stimulating the proliferation of allogeneic T cells as compared
      with the LPS (P<0.05). Compared with the LPS, low-, medium- and high-dose
      astilbin could decrease IL-2 and INF-mu secretion from T cells in MLR but had no
      effect on IL-10 secretion. CONCLUSION: Astilbin can inhibit maturation of mouse
      bone marrow-derived DCs with dose-dependent effect and exert negative effects on
      immunologic function of the DCs.

PMID- 20141738
TI  - [Effects of Naoerkang on expressions of beta-amyloid peptide 1-42 and neprilysin
      in hippocampus in a rat model of Alzheimer's disease].
AB  - OBJECTIVE: To investigate the effects of Naoerkang (NEK), a compound traditional
      Chinese herbal medicine, on the expressions of beta-amyloid peptide 1-42 (Abeta(1
      42)) and neprilysin (NEP) in hippocampal tissues in a rat model of Alzheimer's
      disease (AD). METHODS: Forty-eight male SD rats were randomly divided into normal
      control group, untreated group, piracetam group, low-dose NEK group, medium-dose
      NEK group, and high-dose NEK group, with 8 rats in each group. Five microliters
      of Abeta(1-42) (2 microg/microL) were injected into CA1 area of hippocampus in
      rat to establish AD model whereas the normal control rats were injected with same
      volume of normal saline for comparison. The rats in the NEK groups were treated
      respectively with high-, medium- and low-dose [60, 30, 15 g/(kg.d)] NEK for 28
      days consecutively; piracetam [0.375 g/(kg.d)] was intragastrically administered
      to rats in the piracetam group; and normal saline was applied in the control and
      untreated groups. Y-maze test was used for behavioral study to test the learning
      and memory abilities of rats in different groups. The expressions of Abeta(1-42)
      and NEP in hippocampus were determined by immunohistochemical method, and the
      results were analyzed by image acquisition and analysis system. RESULTS:
      Injection of Abeta(1-42) could induce learning and memory dysfunction and up
      regulate Abeta(1-42) expression in hippocampal tissue in rats of the untreated
      group. Compared with the normal control group, the abilities of learning and
      memory of rats in the untreated group were significantly decreased (P<0.01) and
      the expression of Abeta(1-42) was significantly increased (P<0.01) after model
      establishment. After 28-day administration of NEK and piracetam, the abilities of
      learning and memory of AD rats in piracetam and low-dose, medium-dose and high
      dose NEK groups were significantly improved as compared with the untreated group
      (P<0.01 or P<0.05); the expression of Abeta(1-42) in hippocampal tissues was
      decreased (P<0.01 or P<0.05) and the expression of NEP was increased (P<0.01 or
      P<0.05), especially in the high-dose NEK group. CONCLUSION: NEK can play the role
      of anti-dementia by increasing the expression of NEP in hippocampal tissues of AD
      rats so as to reduce the quantity of AAbeta(1-42) and by improving the ability of
      learning and memory of rats with AD.

PMID- 20141739
TI  - [Effects of Yiguanjian Decoction on liver cirrhosis formation:a differential
      proteomics study in rats].
AB  - OBJECTIVE: To investigate the effects of Yiguanjian Decoction, a compound
      traditional Chinese herbal medicine, on rats with cirrhosis based on the method
      of differential proteomics. METHODS: Wistar male rats (n=48) were randomly
      divided into normal control group (n=12) and model-making group (n=36). Rat
      cirrhosis model was established by intraperitoneal injection of 50% carbon
      tetrachloride (CCl4) plus olive oil solution (1 mL/kg, twice weekly for 9 weeks).
      After 3- and 6-week injection, 6 rats each time were sacrificed for dynamic
      observation before medicine intervention, and the 24 remained rats were randomly
      divided into untreated group (n=12) and Yiguanjian Decoction group (n=12) at the
      first day of the 7th week. All animals were sacrificed by the end of the 9th
      week, and total protein of liver tissue was isolated by two-dimensional gel
      electrophoresis (2-DE); some differentially expressed protein spots were analyzed
      and identified by matrix-assisted laser desorption/ionization two-stage time-of
      flight mass spectrometry (MALDI-TOF/TOF-MS) and database querying. Protein
      expressions of Cu/Zn superoxide dismutase (Cu/Zn SOD) and DJ-1 were validated by
      Western blot and immunohistochemical methods. RESULTS: 2-DE maps with high
      resolution and good repeatability were obtained. In all 50 protein spots
      identified by MALDI-TOF/TOF-MS and database querying, there were 5 protein spots
      related to oxidative stress named Cu/Zn SOD, DJ-1, glutathione synthetase,
      glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2
      respectively. Compared with the normal control group, expressions of Cu/Zn SOD,
      DJ-1, glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2
      in the untreated group were decreased significantly. Expressions of Cu/Zn SOD and
      aldo-keto reductase family 7, A2 were decreased time-dependently. Compared with
      the untreated group in 9th week, protein expressions of Cu/Zn SOD, DJ-1,
      glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2 in
      the Yiguanjian Decoction groups were increased significantly while expression of
      glutathione synthetase was decreased notably. Western blot and
      immunohistochemical results of Cu/Zn SOD and DJ-1 expressions coincided with
      proteomics results. CONCLUSION: Anti-oxidative depression is a key pathological
      change of cirrhosis induced by CCl4 in rats, and increasing expression of
      proteins related to anti-oxidative stress may be a major mechanism of Yiguanjian
      Decoction in treating cirrhosis induced by CCl4 effectively.

PMID- 20141740
TI  - [Effects of Yiniao Recipe on serum antidiuretic hormone level and plasma ratio of
      cAMP to cGMP in rats with kidney-yang deficiency].
AB  - OBJECTIVE: To investigate the effects of Yiniao Recipe, a compound traditional
      Chinese herbal medicine, on contents of serum antidiuretic hormone, and plasma
      cyclic adenosine monophosphate and cyclic guanosine monophosphate in rats with
      kidney-yang deficiency. METHODS: Forty male Wistar rats were randomly divided
      into blank control group, untreated group, desmopressin (Minirin) group, low-dose
      Yiniao Recipe group and high-dose Yiniao Recipe group, with 8 rats in each group.
      Rats in the blank control group were injected with 0.2 mL normal saline, and rats
      in the other groups were given intramuscular injection of hydrocortisone 25
      mg/kg, 1 time daily for 21 consecutive days; from the 8th day of injection, rats
      were given double distilled water, Minirin, and high- and low-dose Yiniao Recipe
      respectively for 30 days. Before and after treatment, 24-hour urine volume was
      observed, and serum antidiuretic hormone (AVP) as well as plasma cyclic adenosine
      monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) contents were
      detected by enzyme-linked immunosorbent assay. The cAMP/cGMP ratio and
      morphological changes in renal tissues were also observed. RESULTS: Compared with
      blank control group, 24-hour urine volume, serum AVP content and cAMP/cGMP ratio
      in the untreated group were decreased; compared with the untreated group, Minirin
      and Yiniao Recipe at low and high doses reduced 24-hour urine volume and
      increased serum AVP content and cAMP/cGMP ratio significantly (P<0.05 or P<0.01).
      There were no obvious pathological changes in renal tissue in all groups.
      CONCLUSION: Yiniao Recipe may reduce 24-hour urine volume by increasing serum AVP
      content and regulating the ratio of cAMP to cGMP in kidney-yang deficiency rats.

PMID- 20141741
TI  - [Effects of Qishe Pill on vertebral hyperostosis induced by upright posture in
      rats].
AB  - OBJECTIVE: To observe the effects of Qishe Pill, a compound traditional Chinese
      herbal medicine, on lumbar vertebral bone formation induced by long-time upright
      posture in rats and to investigate the potential mechanism. METHODS: Thirty SD
      rats were randomly divided into normal control group, untreated group and Qishe
      Pill group. The rats in normal control group received no treatment and were
      raised in normal cages. The rats in untreated group and Qishe Pill group were cut
      off forelimbs by operation so as to be forced to adopt an upright posture for 8
      months to induce hyperostosis. Rats in the Qishe Pill group were intragastrically
      administered with Qishe Pill at a dose of 5 g/(kg x d) for 1 month. All rats were
      sacrificed at the 9th month after surgery and all lumbar vertebrae were harvested
      for detection. Safranin O/fast green staining and picrosirius red staining were
      used to observe pathological changes. Expressions of type I collagen (ColI), type
      X collagen (ColX), vascular endothelial growth factor (VEGF) and transforming
      growth factor beta1 (TGF-beta1) in the 5th lumbar vertebra (L(5)) were detected
      by immunohistochemical method. Expressions of type I collagen alpha2
      (Col1alpha2), type X collagen alpha1 (Col10alpha1), TGF-beta1, and VEGF and runt
      related transcription factor 2 (Runx2) mRNAs in L(1)-L(3) were detected by real
      time fluorescent quantitation reverse transcription-polymerase chain reaction.
      RESULTS: Safranin O/fast green staining showed that in the untreated group, non
      matrix components increased at marginal lumbar vertebra and intervertebral disc
      junction, and hyperostosis appeared. However, no obvious change was observed in
      the normal control group. Non-matrix components decreased at the same location in
      Qishe Pill group as compared with the untreated group. Picrosirius red staining
      showed compact collagens at marginal lumbar vertebra and intervertebral disc
      junction in the normal control group, however, Col I and ColX increased at the
      same location in the untreated group. In the Qishe Pill group, it showed more
      compact collagens, especially ColI. Compared with normal control group,
      expressions of ColX, VEGF and TGF-beta1 were increased at marginal lumbar
      vertebra and intervertebral disc junction in the untreated group. ColX and VEGF
      expressions decreased in the Qishe Pill group as compared with the untreated
      group. Col10alpha1 and Runx2 mRNA expressions were down-regulated by Qishe Pill
      (P<0.01). CONCLUSION: Qishe Pill may delay hyperostosis at marginal lumbar
      vertebra and intervertebral disc junction, which may be related to reducing type
      X collagen and Runx2 expressions.

PMID- 20141742
TI  - [Effects of Huangqi Guizhi Wuwu Decoction given by different administration
      methods on rats with frostbite and the mechanism].
AB  - OBJECTIVE: To establish a rat model of frostbite and to evaluate the effects of
      different administration methods of Huangqi Guizhi Wuwu Decoction (HGWD), a
      compound traditional Chinese herbal medicine for warming meridians to disperse
      cold, on rats with frostbite. METHODS: Frostbite in rats was induced by the
      method of soaking feet in hypothermia ethanol-water mixture. Levels of
      interleukin-6 (IL-6), tumor necrosis factor-beta (TNF-beta), thromboxane B(2)
      (TXB(2)) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)) in serum of rats
      treated with different administration methods of HGWD, such as oral
      administration (Oral HGWD), soak (Soak HGWD), and oral administration plus soak
      (Oral-soak HGWD), were tested by enzyme-linked immunosorbent assay. RESULTS: IL
      6, TNF-beta, TXB(2) levels were significantly higher (P<0.01) and 6-keto-PGFbeta
      level was lower (P<0.01) in serum of rats in the untreated group than in the
      normal control group. Compared with the untreated group, the level of IL-6
      obviously decreased (P<0.05) in serum of the rats treated by oral HGWD, while no
      significant decrease (P>0.05) was observed in the soak HGWD group, and there was
      no interaction (P>0.05) between the two administration methods in regulating the
      level of IL-6. The levels of TNF-beta obviously decreased (P<0.01, P<0.05) in
      serum of the rats treated by oral and soak HGWD, and there was interaction
      between the two administration methods. The level of TNF-beta in the oral HGWD
      group was significantly lower than that in the soak HGWD group (P<0.01). Compared
      with the untreated group, level of TXB(2) in oral HGWD or soak HGWD group did not
      decrease significantly (P>0.05) and there was no interaction (P>0.05) between the
      two administration methods. The level of 6-keto-PGF(1alpha) was obviously
      increased (P<0.01) in serum of the rats treated by oral HGWD, while there was no
      significant decrease (P>0.05) in the soak HGWD group as compared with the
      untreated group, and there was interaction (P<0.05) between the two
      administration methods in regulating the level of 6-keto-PGF(1alpha). CONCLUSION:
      Rats with frostbite has immunologic dysfunction and a state of forming thrombus
      easily. The oral-soak HGWD can improve frostbite of local skin in rats. The
      therapeutic mechanism of HGWD may be to regulate the dysfunction of immune system
      and the imbalance of TXB(2)-PGF(1alpha).

PMID- 20141743
TI  - [Statistical analysis for data of multidimensional contingency table with SAS
      software package (Part four)].

PMID- 20141744
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      an analysis of the Diagnostics (Part 6).

PMID- 20141745
TI  - [English translation of traditional Chinese medicine based on relevance theory].

PMID- 20141747
TI  - A blind spot in confocal reflection microscopy: the dependence of fiber
      brightness on fiber orientation in imaging biopolymer networks.
AB  - We investigate the dependence of fiber brightness on three-dimensional fiber
      orientation when imaging biopolymer networks with confocal reflection microscopy
      (CRM) and confocal fluorescence microscopy (CFM). We compare image data of
      fluorescently labeled type I collagen networks concurrently acquired using each
      imaging modality. For CRM, fiber brightness decreases for more vertically
      oriented fibers, leaving fibers above approximately 50 degrees from the imaging
      plane entirely undetected. As a result, the three-dimensional network structure
      appears aligned with the imaging plane. In contrast, CFM data exhibit little
      variation of fiber brightness with fiber angle, thus revealing an isotropic
      collagen network. Consequently, we find that CFM detects almost twice as many
      fibers as are visible with CRM, thereby yielding more complete structural
      information for three-dimensional fiber networks. We offer a simple explanation
      that predicts the detected fiber brightness as a function of fiber orientation in
      CRM.

PMID- 20141748
TI  - Physical model of the dynamic instability in an expanding cell culture.
AB  - Collective cell migration is of great significance in many biological processes.
      The goal of this work is to give a physical model for the dynamics of cell
      migration during the wound healing response. Experiments demonstrate that an
      initially uniform cell-culture monolayer expands in a nonuniform manner,
      developing fingerlike shapes. These fingerlike shapes of the cell culture front
      are composed of columns of cells that move collectively. We propose a physical
      model to explain this phenomenon, based on the notion of dynamic instability. In
      this model, we treat the first layers of cells at the front of the moving cell
      culture as a continuous one-dimensional membrane (contour), with the usual
      elasticity of a membrane: curvature and surface-tension. This membrane is active,
      due to the forces of cellular motility of the cells, and we propose that this
      motility is related to the local curvature of the culture interface; larger
      convex curvature correlates with a stronger cellular motility force. This shape
      force relation gives rise to a dynamic instability, which we then compare to the
      patterns observed in the wound healing experiments.

PMID- 20141749
TI  - Conformational state-dependent anion binding in prestin: evidence for allosteric
      modulation.
AB  - Outer hair cells boost auditory performance in mammals. This amplification relies
      on an expansive array of intramembranous molecular motors, identified as prestin,
      that drive somatic electromotility. By measuring nonlinear capacitance, the
      electrical signature of electromotility, we are able to assess prestin's
      conformational state and interrogate the effectiveness of anions on prestin's
      activity. We find that the affinity of anions depends on the state of prestin
      that we set with a variety of perturbations (in membrane tension, temperature,
      and voltage), and that movement into the expanded state reduces the affinity of
      prestin for anions. These data signify that anions work allosterically on
      prestin. Consequently, anions are released from prestin's binding site during
      expansion, i.e., during hyperpolarization. This is at odds with the extrinsic
      voltage sensor model, which suggests that prestin-bound intracellular anions are
      propelled deep into the membrane. Furthermore, we hypothesize that prestin's
      susceptibility to many biophysical forces, and notably its piezoelectric nature,
      may reflect anion interactions with the motor.

PMID- 20141750
TI  - Accessibility of the CLC-0 pore to charged methanethiosulfonate reagents.
AB  - Using the substituted-cysteine-accessibility method, we previously showed that a
      cysteine residue introduced to the Y512 position of CLC-0 was more rapidly
      modified by a negatively charged methanethiosulfonate (MTS) reagent, 2
      sulfonatoethyl MTS (MTSES), than by the positively charged 2
      (trimethylammonium)ethyl MTS (MTSET). This result suggests that a positive
      intrinsic pore potential attracts the negatively charged MTS molecule. In this
      study, we further test this hypothesis of a positive pore potential in CLC-0 and
      find that the preference for the negatively charged MTS is diminished
      significantly in modifying the substituted cysteine at a deeper pore position,
      E166. To examine this conundrum, we study the rates of MTS inhibitions of the
      E166C current and those of the control mutant current from E166A. The results
      suggest that the inhibition of E166C by intracellularly applied MTS reagents is
      tainted by the modification of an endogenous cysteine, C229, located at the
      channel's dimer interface. After this endogenous cysteine is mutated, CLC-0
      resumes its preference for selecting MTSES in modifying E166C, reconfirming the
      idea that the pore of CLC-0 is indeed built with a positive intrinsic potential.
      These experiments also reveal that MTS modification of C229 can inhibit the
      current of CLC-0 depending on the amino acid placed at position 166.

PMID- 20141751
TI  - Systematic study of anharmonic features in a principal component analysis of
      gramicidin A.
AB  - We use principal component analysis (PCA) to detect functionally interesting
      collective motions in molecular-dynamics simulations of membrane-bound gramicidin
      A. We examine the statistical and structural properties of all PCA eigenvectors
      and eigenvalues for the backbone and side-chain atoms. All eigenvalue spectra
      show two distinct power-law scaling regimes, quantitatively separating large from
      small covariance motions. Time trajectories of the largest PCs converge to
      Gaussian distributions at long timescales, but groups of small-covariance PCs,
      which are usually ignored as noise, have subdiffusive distributions. These non
      Gaussian distributions imply anharmonic motions on the free-energy surface. We
      characterize the anharmonic components of motion by analyzing the mean-square
      displacement for all PCs. The subdiffusive components reveal picosecond-scale
      oscillations in the mean-square displacement at frequencies consistent with
      infrared measurements. In this regime, the slowest backbone mode exhibits tilting
      of the peptide planes, which allows carbonyl oxygen atoms to provide surrogate
      solvation for water and cation transport in the channel lumen. Higher-frequency
      modes are also apparent, and we describe their vibrational spectra. Our findings
      expand the utility of PCA for quantifying the essential features of motion on the
      anharmonic free-energy surface made accessible by atomistic molecular-dynamics
      simulations.

PMID- 20141752
TI  - Electrostatic tuning of cellular excitability.
AB  - Voltage-gated ion channels regulate the electric activity of excitable tissues,
      such as the heart and brain. Therefore, treatment for conditions of disturbed
      excitability is often based on drugs that target ion channels. In this study of a
      voltage-gated K channel, we propose what we believe to be a novel pharmacological
      mechanism for how to regulate channel activity. Charged lipophilic substances can
      tune channel opening, and consequently excitability, by an electrostatic
      interaction with the channel's voltage sensors. The direction of the effect
      depends on the charge of the substance. This was shown by three compounds sharing
      an arachidonyl backbone but bearing different charge: arachidonic acid, methyl
      arachidonate, and arachidonyl amine. Computer simulations of membrane
      excitability showed that small changes in the voltage dependence of Na and K
      channels have prominent impact on excitability and the tendency for repetitive
      firing. For instance, a shift in the voltage dependence of a K channel with -5 or
      +5 mV corresponds to a threefold increase or decrease in K channel density,
      respectively. We suggest that electrostatic tuning of ion channel activity
      constitutes a novel and powerful pharmacological approach with which to affect
      cellular excitability.

PMID- 20141753
TI  - Ion conduction in ligand-gated ion channels: Brownian dynamics studies of four
      recent crystal structures.
AB  - Four x-ray crystal structures of prokaryotic homologs of ligand-gated ion
      channels have recently been determined: ELIC from Erwinia chrysanthemi, two
      structures of a proton-activated channel from Gloebacter violaceus (GLIC1 and
      GLIC2) and that of the E221A mutant (GLIC1M). The availability of numerous
      structures of channels in this family allows for aspects of channel gating and
      ion conduction to be examined. Here, we determine the likely conduction states of
      the four structures as well as IV curves, ion selectivity, and steps involved in
      ion permeation by performing extensive Brownian dynamics simulations. Our results
      show that the ELIC structure is indeed nonconductive, but that GLIC1 and GLIC1M
      are both conductive of ions with properties different from those seen in
      experimental studies of the channel. GLIC2 appears to reflect an open state of
      the channel with a predicted conductance of 10.8-12.4 pS in 140 mM NaCl solution,
      which is comparable to the experimental value 8 +/- 2 pS. The extracellular
      domain of the channel is shown to have an important influence on the channel
      current, but a less significant role in ion selectivity.

PMID- 20141754
TI  - Manipulation of magnetically labeled and unlabeled cells with mobile magnetic
      traps.
AB  - A platform of discrete microscopic magnetic elements patterned on a surface
      offers dynamic control over the motion of fluid-borne cells by reprogramming the
      magnetization within the magnetic bits. T-lymphocyte cells tethered to magnetic
      microspheres and untethered leukemia cells are remotely manipulated and guided
      along desired trajectories on a silicon surface by directed forces with average
      speeds up to 20 microm/s. In addition to navigating cells, the microspheres can
      be operated from a distance to push biological and inert entities and act as
      local probes in fluidic environments.

PMID- 20141755
TI  - Transversal stiffness and Young's modulus of single fibers from rat soleus muscle
      probed by atomic force microscopy.
AB  - The structural integrity of striated muscle is determined by extra-sarcomere
      cytoskeleton that includes structures that connect the Z-disks and M-bands of a
      sarcomere to sarcomeres of neighbor myofibrils or to sarcolemma. Mechanical
      properties of these structures are not well characterized. The surface structure
      and transversal stiffness of single fibers from soleus muscle of the rat were
      studied with atomic force microscopy in liquid. We identified surface regions
      that correspond to projections of the Z-disks, M-bands, and structures between
      them. Transversal stiffness of the fibers was measured in each of these three
      regions. The stiffness was higher in the Z-disk regions, minimal between the Z
      disks and the M-bands, and intermediate in the M-band regions. The stiffness
      increased twofold when relaxed fibers were maximally activated with calcium and
      threefold when they were transferred to rigor (ATP-free) solution. Transversal
      stiffness of fibers heavily treated with Triton X-100 was about twice higher than
      that of the permeabilized ones, however, its regional difference and the
      dependence on physiological state of the fiber remained the same. The data may be
      useful for understanding mechanics of muscle fibers when it is subjected to both
      axial and transversal strain and stress.

PMID- 20141756
TI  - Recognition and binding of a helix-loop-helix peptide to carbonic anhydrase
      occurs via partly folded intermediate structures.
AB  - We have studied the association of a helix-loop-helix peptide scaffold carrying a
      benzenesulfonamide ligand to carbonic anhydrase using steady-state and time
      resolved fluorescence spectroscopy. The helix-loop-helix peptide, developed for
      biosensing applications, is labeled with the fluorescent probe dansyl, which
      serves as a polarity-sensitive reporter of the binding event. Using maximum
      entropy analysis of the fluorescence lifetime of dansyl at 1:1 stoichiometry
      reveals three characteristic fluorescence lifetime groups, interpreted as
      differently interacting peptide/protein structures. We characterize these
      peptide/protein complexes as mostly bound but unfolded, bound and partly folded,
      and strongly bound and folded. Furthermore, analysis of the fluorescence
      anisotropy decay resulted in three different dansyl rotational correlation times,
      namely 0.18, 1.2, and 23 ns. Using the amplitudes of these times, we can
      correlate the lifetime groups with the corresponding fluorescence anisotropy
      component. The 23-ns rotational correlation time, which appears with the same
      amplitude as a 17-ns fluorescence lifetime, shows that the dansyl fluorophore
      follows the rotational diffusion of carbonic anhydrase when it is a part of the
      folded peptide/protein complex. A partly folded and partly hydrated interfacial
      structure is manifested in an 8-ns dansyl fluorescence lifetime and a 1.2-ns
      rotational correlation time. This structure, we believe, is similar to a molten
      globule-like interfacial structure, which allows segmental movement and has a
      higher degree of solvent exposure of dansyl. Indirect excitation of dansyl on the
      helix-loop-helix peptide through Forster energy transfer from one or several
      tryptophans in the carbonic anhydrase shows that the helix-loop-helix scaffold
      binds to a tryptophan-rich domain of the carbonic anhydrase. We conclude that
      binding of the peptide to carbonic anhydrase involves a transition from a
      disordered to an ordered structure of the helix-loop-helix scaffold.

PMID- 20141757
TI  - Conformational transitions of subunit epsilon in ATP synthase from thermophilic
      Bacillus PS3.
AB  - Subunit epsilon of bacterial and chloroplast F(O)F(1)-ATP synthase is responsible
      for inhibition of ATPase activity. In Bacillus PS3 enzyme, subunit epsilon can
      adopt two conformations. In the "extended", inhibitory conformation, its two C
      terminal alpha-helices are stretched along subunit gamma. In the "contracted",
      noninhibitory conformation, these helices form a hairpin. The transition of
      subunit epsilon from an extended to a contracted state was studied in ATP
      synthase incorporated in Bacillus PS3 membranes at 59 degrees C. Fluorescence
      energy resonance transfer between fluorophores introduced in the C-terminus of
      subunit epsilon and in the N-terminus of subunit gamma was used to follow the
      conformational transition in real time. It was found that ATP induced the
      conformational transition from the extended to the contracted state (half-maximum
      transition extent at 140 microM ATP). ADP could neither prevent nor reverse the
      ATP-induced conformational change, but it did slow it down. Acid residues in the
      DELSEED region of subunit beta were found to stabilize the extended conformation
      of epsilon. Binding of ATP directly to epsilon was not essential for the ATP
      induced conformational change. The ATP concentration necessary for the half
      maximal transition (140 microM) suggests that subunit epsilon probably adopts the
      extended state and strongly inhibits ATP hydrolysis only when the intracellular
      ATP level drops significantly below the normal value.

PMID- 20141758
TI  - Solution structures of rat amylin peptide: simulation, theory, and experiment.
AB  - Amyloid deposits of amylin in the pancreas are an important characteristic
      feature found in patients with Type-2 diabetes. The aggregate has been considered
      important in the disease pathology and has been studied extensively. However, the
      secondary structures of the individual peptide have not been clearly identified.
      In this work, we present detailed solution structures of rat amylin using a
      combination of Monte Carlo and molecular dynamics simulations. A new Monte Carlo
      method is presented to determine the free energy of distinct biomolecular
      conformations. Both folded and random-coil conformations of rat amylin are
      observed in water and their relative stability is examined in detail. The former
      contains an alpha-helical segment comprised of residues 7-17. We find that at
      room temperature the folded structure is more stable, whereas at higher
      temperatures the random-coil structure predominates. From the configurations and
      weights we calculate the alpha-carbon NMR chemical shifts, with results that are
      in reasonable agreement with experiments of others. We also calculate the
      infrared spectrum in the amide I stretch regime, and the results are in fair
      agreement with the experimental line shape presented herein.

PMID- 20141759
TI  - A repulsive electrostatic mechanism for protein export through the type III
      secretion apparatus.
AB  - Many Gram-negative bacteria initiate infections by injecting effector proteins
      into host cells through the type III secretion apparatus, which is comprised of a
      basal body, a needle, and a tip. The needle channel is formed by the assembly of
      a single needle protein. To explore the export mechanisms of MxiH needle protein
      through the needle of Shigella flexneri, an essential step during needle
      assembly, we have performed steered molecular dynamics simulations in implicit
      solvent. The trajectories reveal a screwlike rotation motion during the export of
      nativelike helix-turn-helix conformations. Interestingly, the channel interior
      with excessive electronegative potential creates an energy barrier for MxiH to
      enter the channel, whereas the same may facilitate the ejection of the effectors
      into host cells. Structurally known basal regions and ATPase underneath the basal
      region also have electronegative interiors. Effector proteins also have
      considerable electronegative potential patches on their surfaces. From these
      observations, we propose a repulsive electrostatic mechanism for protein
      translocation through the type III secretion apparatus. Based on this mechanism,
      the ATPase activity and/or proton motive force could be used to energize the
      protein translocation through these nanomachines. A similar mechanism may be
      applicable to macromolecular channels in other secretion systems or viruses
      through which proteins or nucleic acids are transported.

PMID- 20141760
TI  - The polymer brush model of neurofilament projections: effect of protein
      composition.
AB  - Applying self-consistent field theory, we consider a coarse-grained model for the
      polymerlike projections of neurofilament (NF) proteins that form a brush
      structure around neurofilaments. We focus on effects of molecular composition,
      which is the relative occurrence of NF-H, NF-M, and NF-L proteins, on the
      organization of NF projection domains. We consider NF brushes with selectively
      truncated projections, and with a varied ratio L:H:M of constituent tails. Our
      conclusion is that the NF brush structure is remarkably tolerant with respect to
      the variation in M and H chains. Results compare favorably with experimental data
      on model animals, provided that due attention is paid on the level of
      phosphorylation of the KSP repeats.

PMID- 20141761
TI  - Electrostatic solvation energy for two oppositely charged ions in a solvated
      protein system: salt bridges can stabilize proteins.
AB  - Born-type electrostatic continuum methods have been an indispensable ingredient
      in a variety of implicit-solvent methods that reduce computational effort by
      orders of magnitude compared to explicit-solvent MD simulations and thus enable
      treatment using larger systems and/or longer times. An analysis of the
      limitations and failures of the Born approaches serves as a guide for fundamental
      improvements without diminishing the importance of prior works. One of the major
      limitations of the Born theory is the lack of a liquidlike description of the
      response of solvent dipoles to the electrostatic field of the solute and the
      changes therein, a feature contained in the continuum Langevin-Debye (LD) model
      applied here to investigate how Coulombic interactions depend on the location of
      charges relative to the protein/water boundary. This physically more realistic LD
      model is applied to study the stability of salt bridges. When compared head to
      head using the same (independently measurable) physical parameters (radii,
      dielectric constants, etc.), the LD model is in good agreement with observations,
      whereas the Born model is grossly in error. Our calculations also suggest that a
      salt bridge on the protein's surface can be stabilizing when the charge
      separation is < or =4 A.

PMID- 20141762
TI  - Single protein molecule mapping with magnetic atomic force microscopy.
AB  - Understanding the structural organization and distribution of proteins in
      biological cells is of fundamental importance in biomedical research. The use of
      conventional fluorescent microscopy for this purpose is limited due to its
      relatively low spatial resolution compared to the size of a single protein
      molecule. Atomic force microscopy (AFM), on the other hand, allows one to achieve
      single-protein resolution by scanning the cell surface using a specialized ligand
      coated AFM tip. However, because this method relies on short-range interactions,
      it is limited to the detection of binding sites that are directly accessible to
      the AFM tip. We developed a method based on magnetic (long-range) interactions
      and applied it to investigate the structural organization and distribution of
      endothelin receptors on the surface of smooth muscle cells. Endothelin receptors
      were labeled with 50-nm superparamagnetic microbeads and then imaged with
      magnetic AFM. Considering its high spatial resolution and ability to "see"
      magnetically labeled proteins at a distance of up to 150 nm, this approach may
      become an important tool for investigating the dynamics of individual proteins
      both on the cell membrane and in the submembrane space.

PMID- 20141763
TI  - Spectral tuning of the photoactive yellow protein chromophore by H-bonding.
AB  - Spectral tuning in the photoactive yellow protein (PYP) is investigated by
      performing gas-phase absorption measurements on a PYP-model chromophore with two
      water molecules hydrogen-bonded to it. The photoabsorption maximum shows an
      unusually large blue shift of 0.71 eV in going from the bare to the hydrogen
      bonded chromophore. It is concluded that several interactions within the PYP
      protein are mutually cancelling each other, yielding an absorption maximum that
      is close to the absorption maximum of the bare chromophore. The system breaks
      apart upon photoexcitation in the gas phase by releasing the two water molecules,
      leaving the chromophore itself intact. The hydrogen-bonding interactions thus
      play an important role in stabilizing the gas phase chromophore against
      photofragmentation. The relaxation dynamics for the breakup process was also
      studied, and the timescale of relaxation via fragmentation was found to be < 25
      ns.

PMID- 20141764
TI  - Quantitative determination of spatial protein-protein correlations in
      fluorescence confocal microscopy.
AB  - To quantify spatial protein-protein proximity (colocalization) in paired
      microscopic images of two sets of proteins labeled by distinct fluorophores, we
      showed that the cross-correlation and the autocorrelation functions of image
      intensity consisted of fast and slowly decaying components. The fast component
      resulted from clusters of proteins specifically labeled, and the slow component
      resulted from image heterogeneity and a broadly-distributed background. To better
      evaluate spatial proximity between the two specifically labeled proteins, we
      extracted the fast-decaying component by fitting the sharp peak in correlation
      functions to a Gaussian function, which was then used to obtain protein-protein
      proximity index and the Pearson's correlation coefficient. We also employed the
      median-filter method as a universal approach for background reduction to minimize
      nonspecific fluorescence. We illustrated our method by analyzing computer
      simulated images and biological images.

PMID- 20141765
TI  - Special issue on neuropeptides in stress and addiction: Overview.

PMID- 20141767
TI  - Update of cerebral vascular disease: issues for the primary care physician.

PMID- 20141768
TI  - Cerebral vascular disease.

PMID- 20141769
TI  - [Mental health risk states of 15- to 25-year-olds and their environment ].

PMID- 20141770
TI  - Cerebral maturation in adolescence: behavioral vulnerability.
AB  - Recent neurodevelopmental research has been focusing on the transition period of
      adolescence into adulthood. This growing interest was spurred by the long
      standing realization of the high cost of this transition period in terms of
      morbidity and mortality, and the emergence of research tools that permit direct
      examination of brain function in humans. The cost of reaching adulthood is
      understood as resulting from the typical behavioral and environmental changes
      that accompany adolescence [4]. The present review describes how the current
      research helps formulate neurobiological models that can be used to guide future
      work. One example of such a model, the triadic neural systems model [8], will be
      examined in more detail. This review will proceed in three stages. First, we will
      show how neural development results from the confluence of maturational changes
      that are quantitatively and qualitatively heterogeneous across brain regions,
      neurochemical and molecular systems. This normative developmental heterogeneity
      is translated into typical adolescent behavioral patterns, including risk-taking,
      novelty-seeking, emotional intensity and lability, and peer-group social primacy
      [5, 9]. Second, based on the notion that motivated behavior can be operationally
      decomposed into the three core modules of approach, avoidance and control, any
      alteration in the balance of these three core entities can affect behavior in
      unique ways. This formulation will serve as the foundation of the neural systems
      model framework proposed in this review. Third, functional neuroimaging is being
      used to examine how neural systems underlie this balance within the neural
      systems model. We will provide a summary of the state of research in this area.
      Finally, we will show how this research is important for understanding not only
      normal development, but also the psychopathology. The role of genetic or
      environmental factors will not be addressed here, despite their critical roles in
      determining and modulating the balance among the nodes of the triadic model.

PMID- 20141771
TI  - [Sociology and epidemiology of consumption of psychoactive substances in
      adolescents].
AB  - Epidemiological monitoring of drug use among adolescents or young adults is a
      major concern for public policy makers. This surveillance requires the use of
      adapted methodological solutions. This article presents how far epidemiological
      surveillance is a useful tool for monitoring drug use at adolescence. It also
      presents the results of the French general population surveys among adolescents
      or young adults, and the trends in the last decade. It relies on a survey among
      17 years old adolescents and a general population survey among adults (analysis
      is restricted to people aged 18-25). A European school survey among 16 years old
      is also presented to compare the French situation to other European countries
      levels of use. The use of psychoactive substance increases fast with age during
      adolescence however results vary from one substance to another. Since year 2000,
      tobacco use is decreasing when alcohol use frequency appears stable between 2003
      and 2005, although drunkenness has increased from 2000 to 2005. The frequency of
      lifetime or occasional use of cannabis appears stable since 2000. Among 17 years
      old, the proportion of regular users of cannabis has been stable between 2000 and
      2005. Finally, the prevalence of ecstasy and cocaine increased during this period
      of time, despite being less than 4%, but the levels of the other illicit
      substances are low and stable. The results on alcohol variables and tobacco use
      in France are rather close to the European average. Four out of five 16 years old
      students had drunk alcohol during the past 12 months and 36 percent had been
      drunk during this period (vs 39% in the average European country). About one
      third of the students had smoked cigarettes during the past 30 days (close to the
      29% in the average European country). The use of cannabis, however, is clearly
      more prevalent in France. Almost one-third (31%) of the students had already used
      cannabis (vs 19% in the average European country). The use of inhalants was
      reported by 12 percent, which is close to the average, while 15 percent of the
      students had used tranquillisers or sedatives without a doctor's prescription,
      which is more than twice the European average (6%).

PMID- 20141772
TI  - [Student's use of illicit drugs: a survey in a preventive health service].
AB  - INTRODUCTION: The use of illicit drugs by students and the possible psychological
      repercussions in this population of young adults is an important public health
      issue. While some data in the literature suggest a relationship between cannabis
      and the occurrence of mental health disorders, and in particular psychotic
      illnesses, epidemiologic surveys have shown that cannabis is the most consumed
      illicit drug in France. AIM OF THE STUDY: To carry out a quantitative and
      qualitative epidemiological investigation of substance use within a student
      population seen during their mandatory preventive health visit at the University
      medical facility. METHOD: Students were asked to take part in an investigation of
      their substance consumption and their individual experiences with cannabis in
      particular. Personality autoquestionnaires were performed and the psychotomimetic
      effects of cannabis were investigated with substance use within a student
      population seen during their mandatory preventive health visit at the University
      medical facility. RESULTS: A total of 3,807 students took part in the survey with
      a response rate of approximately 50%. Preliminary results relating to a subsample
      of this study are presented here (n = 880, mean age 20 years, 65% women). 44% of
      the students consumed cannabis at least once in their life. The prevalence of
      regular consumption in students (at least once a week) was of 18%, 11% had
      periods of daily or close to daily consumptions, and 13% used cannabis in the
      last month. For each of the drugs cocaine, ecstasy (MDMA), and mushrooms
      (psilocybin) the prevalence of experimentation (at least once) was 5% for
      cocaine, 4% for ecstasy and mushrooms, and for LSD the rate was 1,5%. Other
      evaluated substances had a prevalence of consumption lower than 1%. For the first
      cannabis consumptions, a majority of students state to felt "pleasant" effects:
      relaxation (71%) and euphoria (53%). 13% state to have felt effects of anxiety or
      sadness. 25% admit having had difficulties of expression, 24% memory deficits,
      35% trouble with coordination or balance and 39% difficulties of concentration.
      Approximately 16% had impressions of depersonalization and derealization. Lastly,
      some experienced "psychotic-like" effects such as visual (10%) and auditory (6%)
      hallucinations, as well as referential ideas (16%), mistrust or feelings of
      persecution (11%). 26% of the student sample had felt at least one of these last
      four "psychotic-like" effects. DISCUSSION: The results are consistent with the
      idea that the impact of cannabis consumption is highly variable among different
      consumers. Implications for prevention strategies are discussed such as
      educational interventions based on recognition and motivation for change.

PMID- 20141773
TI  - [Motivational interventions: psychosis and cannabis].
AB  - Cannabis use by people suffering from schizophrenia increase relapse rate and
      reduce adhesion to treatment. Motivational interventions could reduce cannabis
      misuse. The motivational interviewing principles and techniques are presented in
      a concrete way as well as the required adaptations to bypass cognitive deficits
      associated with schizophrenia.

PMID- 20141774
TI  - [The interest of "help meeting points" in young people's environment].
AB  - Les "points d'accueil et d'ecoute jeunes" are place where youth or young adult in
      a situation of crisis or in a situation at risk can received help, advices, be
      oriented. Mediation with the familial or social environment can be conducted. The
      primary vocation is to help adolescents to mature and to help parents to "make
      mature". The main modality of action are based on a free access and on a
      reconstruction of the social and or familial relationships around the adolescent,
      in order that the adolescent or young adult can resume a dialog with his
      environment.

PMID- 20141775
TI  - [Psychotic states in young migrants and children of migrants].
AB  - Psychiatric literature documenting increased rates of psychotic illness among
      migrants in European countries has been more and more reported during the past
      two decades. Social causes to this phenomenon have been highlighted. In this
      paper, we review and discuss this literature from the cultural psychiatry
      perspective. We can point three limitations to these works : the definition of
      the studied groups, the cultural validity diagnoses, and the psychic impact of
      migration and its complexity not being considered enough. The above
      considerations lead us to go forward with studies addressing this question. The
      need to construct methodologies addressing psychiatric epidemiology,
      transcultural psychiatry and human sciences is underlined.

PMID- 20141776
TI  - [Bipolar episodes in adolescents: diagnostic issues and follow-up in adulthood].
AB  - BACKGROUND: Little is known on the phenomenology and potential prognosis factors
      of bipolar episodes in adolescents. In particular, very few studies examine this
      issue on inpatients in the European context of free access to care. OBJECTIVE: To
      assess the follow-up in adulthood of acute manic and mixed episodes in
      hospitalized adolescents and the predictive value of psychological testing.
      METHODS: 80 subjects, aged 12 to 20 years, consecutively hospitalized for a manic
      or mixed episode between 1994 and 2003, were contacted in 2005-2006 for a follow
      up assessment. 5 patients refused, 20 were lost, 55 patients were assessed by
      direct and complete interview (67%) or by phone and treating psychiatrist (33%).
      RESULTS: At index episode, the sample was characterized by severe impairment,
      high rates of psychotic features (N = 50, 62,5%), a long duration of stay (mean =
      80,4 days), and an overall good improvement at discharge from hospital (86% very
      much or much improved). Half had a psychological testing before discharge. At
      follow-up (mean average 5 years), 35 patients still had a diagnosis of bipolar
      disorder. Eight changed life-time diagnosis for schizoaffective disorder and 11
      for schizophrenia. Mortality and morbidity were severe with one subject who died
      from cardiac failure, and 91% of patients who had at least one relapse. Patients
      without relapse (N = 5) and patients showing a good social functioning (N = 19)
      remained with a diagnosis of bipolar disorder. Using a clinical global impression
      method, psychological testing (blind with follow-up status) was significantly
      correlated with transition to schizophrenia spectrum disorder. CONCLUSION:
      Contrarily to what is seen in less severe sample of bipolar disorder, changes in
      life time diagnosis can occur during follow-up after a manic or mixed episode in
      adolescence, as many patients are in the schizophrenia spectrum in adulthood.

PMID- 20141777
TI  - [The diversity of approaches for psychopathological disorders in school and
      university surroundings: surprises and paradoxes].
AB  - In this review, we are addressing several issues of the approach of emerging
      mental disorders in school and university by first line professionals: diagnostic
      indicators, on-site care, referring and pathway to care. We will expose our
      unique experience of the "Relais Etudiants Lyceens" a specialized out patient
      unit dedicated for the assessment and brief therapy at the interface between
      school and university health services and specialized public care systems for
      child and adult psychiatry in Paris.

PMID- 20141778
TI  - ["Severity" in the context of depression].

PMID- 20141779
TI  - [Severe depression].

PMID- 20141780
TI  - [Severe depression : which concept ? which criteria].
AB  - Depression is a common disorder considered to be a serious public health problem
      although clinicians encounter very different levels of severity and the treatment
      strategies are tailored according to this variability. There are however no
      consensus criteria to define severe depression. This review presents and
      discusses the different possible qualitative and quantitative options. In the
      international classifications there are three levels of severity of episodes of
      major depression (mild, moderate, severe), which are defined above all on the
      number of diagnostic criteria found. There are other more qualitative severity
      factors : the presence of psychotic symptoms, melancholia and the presence of
      endogenous signs. Pronounced psychomotor retardation and risk of suicide are
      amongst the main clinical severity markers. Quantitative assessment scales for
      the severity of depression can also define severity thresholds for use for
      example in clinical studies. These thresholds are still poorly defined and vary
      between studies. Specific severity scales for melancholic depression or
      depression with psychomotor retardation can also be used in clinical studies for
      these factors, which are central to the concept of severe depression. Overall,
      the inclusion criteria for most studies combine severe depression with
      qualitative (clinicians' judgement) and quantitative (minimum score on a scale)
      aspects.

PMID- 20141781
TI  - [Events of life and links with severe depression at different ages].
AB  - Major depression is a common, severe, chronic, and often life-threatening
      illness. There is a growing body of evidence that, far from being a disease with
      purely psychological manifestations, major depression is a systemic disease with
      deleterious effects on multiple organ systems. Stressful life events have a
      substantial causal association with depression, and there is now compelling
      evidence that even early life stress constitutes a major risk factor for the
      subsequent development of depression. This review will focus on the association
      between severity of depression and diachronic vulnerability across the life-span,
      in terms of events of life, stress, and hormonal modulation, with a special focus
      on depression in young adults, women during postpartum and in depression in
      ederly people. Given the high prevalence of depressive disorders, the significant
      burden and the severity of disease in adolescents and young adults experiencing
      their first episode, they represent a group at high risk of relapse, recurrence,
      comorbidity and suicide to whom early intervention and prevention efforts should
      be targeted. Females exhibit different stress sensitivities than males which
      might contribute to their increased vulnerability for depression and the disease
      exhibit a prevalence among women which is 2-3x higher than in men. The postpartum
      period is considered the time of greatest risk for women to develop major
      depression and postpartum depression affects approximately 15% of women. In old
      age, depression mainly affects those with chronic medical illness, severe
      disability or mental decline. Depression in elderly worsens the outcomes of many
      medical illness and increases mortality. Environmental factors, such as
      isolation, caregiving and bereavement, contribute to further increase
      susceptibility to depression or triggering depression in already vulnerable
      elderly people. Suitable treatment of depression in elderly reduces the symptoms,
      prevents suicidal ideation, improves cognitive and functional status in order to
      improve the recovery of a good quality of life, as well as the mortality risk.

PMID- 20141782
TI  - [Severe depression: recurrence and chronicity].
AB  - This review paper deals with the question of the relationships between clinical
      severity of depression, recurrence risk and chronicity risk. About 60% of the
      subjects with a first episode of major depression will present a second episode
      lifetime. The risk of recurrence increases slightly with the severity of the
      index episode. Conversely, depression severity tends to be slightly higher in
      recurrent episodes as compared with first episodes. This is supported by a few
      studies of consecutive episodes within the same patients but it could also result
      from a selection effect. The risk that a depressive episode is still meeting the
      criteria of a major depressive episode two years after onset is between 10 and
      20%. Neither the severity of the index episode nor its recurrent character
      clearly increases the risk of its chronic evolution. Finally, minor depression
      (as a dysthymic disorder or residual symptoms) increases the risk of a new major
      depressive episode. We may conclude that there are only moderate interactions
      between the clinical severity of depression and the risks of chronicity and
      recurrence. Worsening of one of these three variables will not result into a
      dramatic worsening of the two others. In fact, chronicity and recurrence do not
      specifically contribute to the severity of the next episode, they only contribute
      to the long-term severity of depressive disorders, which is already by itself a
      major issue.

PMID- 20141783
TI  - [Severe depression : specific features of bipolar disorder].
AB  - Bipolar depressions can present all the clinical aspects from a major depressive
      episode with a mild intensity to severe one. However, part of this severity comes
      from the bipolarity by itself. Bipolar disorders belong to the 10 most disabling
      conditions in the world. Moreover, the complexity of bipolar depressions comes
      also from the complexity to treat them. Antidepressants are difficult to use in
      bipolar subjects because the risk of switch, the possible induction of rapid
      cycles or of a chronic dysphoric state. Currently, guidelines are not very
      helpful for the choice of the treatment in case of an acute major depressive
      disorder. Indeed, the current guidelines give the choice between a mood
      stabilizer alone or associated with an antidepressant, either between an
      antipsychotic more or less associated with an antidepressant. A better
      understanding of the clinical heterogeneity of bipolar depression could help to
      solve a part of this complexity.

PMID- 20141784
TI  - [Severe depression and addictions].
AB  - Addictive co-morbidities (or co-occurrent disorder, double diagnosis, associated
      diagnosis) associated with depression are diagnoses which must be made
      independently and not only seen as a cluster as symptoms of the disorder or as
      disorders induced by taking the toxin. The association of an addictive disorder
      with depression raises a prognostic problem as this association results not only
      in mutual worsening of the two disorders but in a further problem of penalising
      access to care with an important sub-diagnosis. This is a common association ;
      however as 30 to 50% of patients admitted to psychiatric units in Europe have a
      mental disorder combined with substance abuse (alcohol, sedatives, cannabis). In
      this article we describe the different findings reported in the literature
      showing how this association is strong and may have consequences in terms of
      delayed diagnosis and prognostic and therapeutic impact. We also show that
      regardless of the origin of the association (attempted self-medication, addiction
      induced depression, consequence of depression or a fortuitous association), dual
      psychiatric and addiction medicine practice is always justified even if this is
      frequently complex because of the ways in which the different facilities
      available to us operate in isolation.

PMID- 20141785
TI  - [Severe depression : morbidity-mortality and suicide].
AB  - The severity of depression is related to its clinical features and also its
      impact in terms of morbidity and mortality. Depression is the most common
      psychiatric disorders associated with suicide and is found in almost one out of
      two cases, in 85% of situations associated with another mental disorder.
      Clinically severe depression also has a 4 to 5 times higher long term risk of
      suicide than mild or moderate depression. Severe depression is also associated
      with significantly increased deaths from natural causes : in absolute terms this
      is similar to the additional mortality rate from suicide. Cardiovascular
      diseases, particularly coronary, are a particular feature of this increased cause
      of natural deaths. These findings justify the development of prevention and
      screening for these diseases in depressed patients.

PMID- 20141786
TI  - [Severe depression : concomitant somatic disease].
AB  - The association of somatic disease with a depressive disorder is not uncommon and
      affects 25% of general hospital inpatient populations. Although not well
      incorporated into management it is a source of mutual worsening of the two
      diseases. Several questions arise with this association. Firstly, it is essential
      to establish whether the depressive disorder is primary or secondary as these
      situations occasionally involve different (and even opposite) diagnostic and
      treatment approaches. It is then important to establish whether or not the
      disorder is adaptatory in nature : although an adaptatory problem does not have
      the same impact as depression on somatic outcome, it can progress to endogenous
      depression. Finally it is essential to identify the extent of suicidal risk,
      which is not only due to the depression but more to the feeling of despair (which
      is common in patients suffering from severe somatic illness). We will then
      examine the severity of these interlinked depressions in terms of the diagnostic
      difficulties (from confusion of symptoms to considering them to be unimportant).
      We shall then describe all of the consequences of the somatic disease on the
      prognosis of the depression and vice versa. Finally we will examine the question
      of severity from the perspective of the most widely studied associated diseases.
      Whilst the presence of an incapacitating somatic disease is a risk factor for
      depression in these vulnerable people, depression associated with the different
      major somatic diseases is a poor prognostic indicator. Somatic co-morbidities are
      still underestimated and are a factor responsible for chronic progression,
      deterioration and increased risk of suicide.

PMID- 20141787
TI  - [Severe depression : life events, patient history].
AB  - The relationships between severe depression, life events and personality are
      complex. However, sexual abuse and maltreatment during childhood contribute
      towards vulnerability to depressive disorders. Maltreatment in childhood does not
      appear to be linked to any particular personality disorder. An << insecure >>
      type of bonding appears to be a vulnerability factor both for anxiety and
      depressive disorders in adulthood.

PMID- 20141788
TI  - [Personality and vulnerability to severe depression].
AB  - Among the available approachs of personality, the presence of a personality
      disorder is the most documented vulnerability factor to severe depression.
      Impulsivity as well as some immature defense mechanisms may also be factors that
      predispose to severe depression.

PMID- 20141789
TI  - [Severe depression : cultural and social factors].
AB  - After first providing a theoretical framework including the contributions of
      social constructivist and biological approaches to the comprehension of mental
      diseases in general and depression in particular, the authors stress the small
      number of publications mentioning a direct link between sociocultural factors and
      the severity of depression. However, there are indirect arguments that are
      classified into two groups : modifications based on the cultures of clinical
      expression (somatisation, delirious ideas) on one hand and the weight of social
      and individual views of depression and of its consequences in terms of
      stigmatisation on the other. These transcultural variations modify the process of
      seeking care and, thus, the progression of the disease towards increased
      severity. The authors point out, in conclusion, that the initial proposition
      could be reversed as some have postulated that the central role occupied by the
      diagnosis of depression is a phenomenon of civilisation or even the symptom of
      the severity of the uneasiness of western society.

PMID- 20141790
TI  - [Severe depression and work].
AB  - The prevalence of depression and processes liable to increase the severity of
      these disorders can be examined both by analysing the changes in the working
      environment and those relating to difficulties in diagnosis and treatment. The
      promotion of excellence, extensive competition in working relationships and the
      rise in different forms of violence, the increase in disadvantaged and unemployed
      populations are the major changes found : these result in an increase in work
      demands and by reduced resources to respond to these. The morbid process is
      liable to be increased due to the dual effect of the social invisibility of the
      disorder and people's isolation. Failure to manage patients and provide care may
      result in a worsening of the consequences of depression in terms of sustained
      incapacity or suicide attempts which are often seen in severe forms of
      depression. The treatment and prevention approach in this situation involves a
      combination of both care offered to the patient and interventions in the working
      environment in order to reduce their pathogenic potential.

PMID- 20141791
TI  - [Severe depression : environmental factors of severe depression : depression in
      parents].
AB  - Depression in parents is a significant risk factor for depression in the
      offspring at all ages, and also modulates depression severity. Depression
      severity increases with the number of parents affected, but the presence of
      grandparents without depression may be protective. Most studies have focused on
      the transmission of maternal depression, however, the few studies examining
      paternal depression observe that it impacts more on behavioral than emotional
      disorders. The genetic component of inter-generational transmission increases
      with the severity of depression. The interaction between parental depression,
      environment and onset of depression in children is complex due to the secondary
      effects of depression which range from in utero disturbances of cortisol
      secretion via the placenta, to poor parenting skills and high rates of family
      conflict and co-morbidity. While pharmaceutical treatment of depression in
      parents reduces the risk in children, it is also necessary to modify secondary
      factors as these may persist in the face of treatment and continue to increase
      risk. A number of questions remain to be explored ; the effect of the age of the
      child when the parent becomes depressed, the differential impact according to the
      child's sex, and the effect of duration of exposure.

PMID- 20141792
TI  - [Severe depression : functional neuroanatomy].
AB  - Depression is a severe disorder to which some individuals are more vulnerable
      than others. The study of the neurocognitive basis of the vulnerability to
      depression is, therefore, of major importance. Several neuroimaging studies have
      shown the persistence of brain dysfunctions in remitted patients. At the
      neuroanatomic level, alterations of the amygdala, ventral, medial and
      dorsolateral prefrontal cortices, cingulate gyrus, hippocampus and basal nuclei,
      and their connections, have been reported. These impairments have been linked to
      altered cognitive and emotional processes including a higher sensitivity to
      specific environmental stimuli, impairment in emotional regulation and diminished
      working memory or inhibition. Moreover, other studies suggest that these
      dysfunctions should be distinguished from those related to the vulnerability to
      suicidal behavior, which should be considered as a specific pathological entity.
      Finally, preliminary studies have underlined the genetic modulation and the
      influence of early traumatic events on brain activations, which underscore the
      developmental features of these alterations. These findings open the door to new
      treatments.

PMID- 20141793
TI  - [Severe depression: genes and the environment].
AB  - Depressed patients with a familial history of depression are usually considered
      as more endogenous, with higher severity, therefore with a worst prognosis
      (regarding for example recurrence risk). The opposition between << neurotic
      stress linked depression >> and << endogeneous-genetically related depression >>
      is being challenge in the present review. Indeed, differences in age at onset and
      selection bias are probably important confusing factors. The existence of an
      interaction between the involved vulnerability genes (G) and the triggering
      stressful events (E) was considered as providing meaningful insight for the
      respective parts of genetics and the environment. Although this approach is even
      more fragile regarding required sample sizes (larger) and the problem of false
      positive results (increased), the G*E approach is seducing as closer to reality,
      the onset of complex disorders being usually explained by those two risk factors.

PMID- 20141794
TI  - [Severe depression : the doctor/patient relationship].
AB  - The relation between doctor and patient is of great importance in clinical
      practice. For treating depression, a patient-centered model of practice helps to
      acquire necessary diagnostic information, but also to understand the patient's
      subjective experience of presenting problems and the patient's psychosocial
      context. That seems to be an important point to focus on in clinical practice, to
      improve the treatment of depressed patients. On the other hand, depressed
      patients with higher involvement in medical decisions have a higher probability
      of improving their symptoms. Interventions to increase patient involvement in
      decision-making may be an important mean of improving care for and outcomes of
      depression. One of the goals clinicians may have, is to achieve shared
      understanding between patient and themselves about the patient's problems and
      their treatment.

PMID- 20141795
TI  - [The treatment barrier as a severity factor in depression].
AB  - The term treatment barrier describes obstacles to the treatment process. These
      obstacles affect the patient: there may be melancholic crypts in encysted trauma
      ; there may be a link rooted to a dead person in the form of attachment to the
      internal object: there are different forms of moral masochism. Barriers relating
      to the therapist may be seen in therapists who take a dogmatic position: the
      therapist must realise these counter-attitudes and their impatience or irritation
      movements. In the patient doctor-interaction, understanding previous treatment
      failures and the relationship style developed with other therapists plays an
      important role. The concept of the negative therapeutic reaction in which any
      clinical progress returns to aggravation must also be investigated.

PMID- 20141796
TI  - [Severe depression : pharmacological treatments].
AB  - Depression is a common illness with a large clinical phenotype, and clinicians
      have numerous guidelines to treat this disorder : many antidepressant drugs are
      available with different pharmacological profiles and stepped strategies are
      proposed to obtain a remission. It exists a relationship between baseline
      depression symptom severity and treatment response and patient with higher levels
      of severity received significantly more intervention visits, more months of
      antidepressant treatment and more antidepressant trials, but there is not
      accepted and consensual definition for severe depression. By using cut-off scores
      on rating scales severe depression is at one extreme of a continuum of severity
      (but scales which serve for quantifying the intensity of the depression with
      thresholds present an interest and also limits, in the current practice, they are
      rarely used), in the other hand some symptoms contributes to severity (psychotics
      features, suicidal ideation), evolution and prognosis is a part of severity too
      (recurrences, chronicity), severe depression can influence a somatic pathology
      contributing to severity (could be considered itself as a major risk factor) and
      have an impact on treatment outcome, finally by its role on morbi-mortality and
      handicap, depression is often a severe disorder. So, concerning the therapeutic
      choices, there are few data to choose specific options because the concept of
      severity in the depression is not still clearly defined in studies and few
      randomized contolled studies have been done in this indication and adapted to
      different modality of the severity expression. Symptom-free remission is a goal
      for treatment in severe depression, but complications have to be considered in
      medication algorithms. In this paper, we review the modalities of prescription of
      antidepressants according to these differences of the severity in depression.

PMID- 20141797
TI  - [Electrostimulation techniques in treatment for severe depression].
AB  - Electroconvulsivotherapy represents a key indication for severe Major Depressive
      Episode (MDE). However, an hospitalization with a general anaesthesia allowing a
      seizure induction followed by an almost systematic post-epileptic delirium
      justifies the development of other brain electrostimulation techniques. Trans
      cranial Magnetic Stimulation (TMS) is a technique which offers to transform an
      electromagnetic field within the brain in an electric one. This therapeutic has
      been approved in 2008 in the MDE indication by the Food and Drug Administration.
      However a better knowledge of brain stimulation parameters such as the number of
      sequences, intensity, frequency, and the brain target, is necessary. Indeed it
      could enable to get some more homogeneous clinical results which will drive to
      the use of this technique in daily practice. Neurosurgical procedures represent
      also a stake for a better treatment of severe chronic and resistant depression.
      Whereas Vagus Nerve Stimulation (DBS) failed to be developed in France, Deep
      Brain Stimulation (DBS) is currently under development in this indication with
      some promising preliminary results.

PMID- 20141798
TI  - [Severe depression : psychological aspects of management].
AB  - Severe depressions are not an easy target for psychotherapy, because of intense
      cognitive disability linked to emotional and motivational symptoms. But
      psychotherapy remains an important tool for the relapse prevention : this is the
      case for cognitive-behavioral therapies (CBT), and, at a lesser level of proof,
      mindfulness-based cognitive therapy (MBCT). Finally, positive psychology (PP)
      will maybe offer in a near future some interventions (on optimism, social link,
      emotional balance...) who shall represent new possibilities in the quest of
      relapse prevention for those vulnerable patients.

PMID- 20141799
TI  - [Severe depression : psychoanalysis].
AB  - The indication for psychoanalysis in severe depression is not clear. And yet,
      demands for this type of intervention are increasing, despite the absence of any
      form of consensus on the subject. Freud considered depression as a failure of
      analytical efforts and, based on this observation, revised his theory, in
      particular to include the notions of narcissism and the death drive. Many
      analysts have been reluctant to follow his teachings on this last point and
      provide depressed patients with analytical-type therapies aimed at restoring
      narcissism. Melanie Klein pushed Freud's ideas about depression even further and
      brought such therapies back to the heart of analytical practice. Jacques Lacan
      took the debate to another level by proposing an overhaul of the principles on
      which analysis has been based. Today, while following certain precautionary
      rules, true psychoanalyses can be proposed to patients with severe depression,
      whether of the bipolar, recurring or even neurotic type that can reach this level
      of severity.

PMID- 20141800
TI  - [The severe depression : a clinical and evolutive reality].

PMID- 20141801
TI  - [Beginning bipolar disorders].

PMID- 20141802
TI  - [Manic polarity of the onset episode of bipolar disorder: clinical and prognostic
      considerations].
AB  - Studies mapping the course of bipolar disorder from the first episode have
      provided important information with regard to the prognosis of the illness in
      patients with a manic episode at onset. Two different approaches have been used
      in these studies. Prospective follow-up studies conducted in the few years
      following the first episode have emphasized the poor symptomatic and functional
      short-term outcome of the patients. Retrospective studies, more relevant to
      address the long-term course of the illness according to the clinical
      characteristics of the first episode, have consistently evidenced that polarity
      at onset is predictive of the dominant polarity of the disorder for a given
      patient. Given the harmful consequences of recurrences on the outcome of the
      illness and the psychosocial functioning of patients, early diagnosis potentially
      allowed by the occurrence of a first manic episode is a critical step toward
      prescribing a mood stabilizer at the beginning of the disorder. Accurate
      knowledge on the clinical characteristics and the course of illness in patients
      with a manic episode at illness onset may help clinicians for developing more
      specific and more relevant therapeutic intervention for these patients.

PMID- 20141803
TI  - [Depressive onset episode of bipolar disorder: clinical and prognostic
      considerations].
AB  - Both retrospective and high-risk individuals prospective studies show that a high
      percentage of patients experience one or more depressive episodes previous the
      diagnosis of bipolar disorder. Depressive onset bipolar disorders begin earlier
      than the ones with a manic onset, have a higher duration, a chronic course with
      frequent recurrences, a depressive dominant polarity, a higher lifetime rate of
      suicidal behaviour, less psychotic symptoms and more rapid cycling. A relation
      between frequent rapid cycling and previous prescription of antidepressants was
      suggested but not rigorously demonstrated. Thus, a high percentage of patients
      presenting a first depressive episode will later develop bipolar disorder.
      Several risk factors of bipolarity have been identified and might be detected
      during each depressive episode by using standardised evaluations and family
      interviews, if necessary. Among them, an early age at first episode, frequent
      recurrences, a family history of bipolar disorder, atypical features and
      hypomanic symptoms are particularly associated with the subsequent development of
      a bipolar disorder. The impact of a high risk of bipolarity on drug prescription
      is unclear ; however, one can strongly recommend to intensifying clinical
      monitoring and to proposing adjunctive psychoeducation.

PMID- 20141804
TI  - [Treatment of a first manic episode].
AB  - When the first episode of mania is not directly related to a somatic or toxic
      disease it indicates bipolar disorder. These former possibilities must always be
      excluded from a laboratory and morphological assessment. They are clinically
      difficult to identify mostly because the clinical presentation is usually
      atypical. Whilst they may occur at any age they mostly involve young people, and
      drug use is common. Psychotic presentations are particularly common as are some
      symptoms such as irritability. Treatment of the acute phase is no different from
      that of other manic episodes although the challenges are very different as whilst
      there is often a risk of functional deterioration after an initial episode this
      risk increases considerably with repeated episodes. It is therefore essential to
      establish a quality treatment alliance as soon as possible which will facilitate
      the introduction, acceptance and adherence to preventative treatment and
      adherence to the different lifestyle recommendations. Clinical studies are needed
      in order to provide more information about the most suitable preventative
      treatment in this population.

PMID- 20141805
TI  - [Treatment of a first depressive episode in bipolar disorder].
AB  - The first episode of bipolar depression needs a combined psychopharmacological,
      psychobehavioural and social treatment strategy but because of the pathological
      severity of the mood episode itself, it specifically requires to achieve total
      symptomatic remission and therefore appropriate treatment of the index episode.
      International recommendations which derive primarily from Anglo-Saxon regulations
      formally restrict the use of antidepressants in view of the risk of mania,
      suggesting that serotoninergic agents be used in preference and recommending the
      prescription of mood regulators or even antipsychotic agents and various stepwise
      associations based on the relative potencies of the pharmacological tools
      available and treatment stages deployed optimally to obtain complete remission.
      Finally, treatment of the episode includes prophylaxis as its initial episode is
      the first presentation of a chronic disease.

PMID- 20141806
TI  - [Premorbid phase of bipolar disorder].
AB  - The study of the premorbid functioning in bipolar disorder allows us to identify
      several risk factors of the disease. First we will present retrospective studies
      of adults or teenagers presenting a bipolar disorder and second the studies
      concerning offspring of parents with bipolar disorder. Despite contradictory
      results and methodological weaknesses, these studies indicate that anxious
      disorders and childhood disruptive behaviour disorders may be useful markers of
      risk for adult bipolar disorder. All these results may open up several
      interesting perspectives for the prevention ant the treatment of bipolar
      disorder.

PMID- 20141807
TI  - [Prodromal phase in bipolar disorder].
AB  - The prodromal phase is generally described as a subsyndromal stage preceding the
      disease onset. The characterization of such phase found its main purpose in
      secondary prevention. Up to now, clinical research relating to this topic in
      mental health has primarily focus on schizophrenic disorders. Over the last
      years, some studies have applied similar methods in order to characterize a
      preclinical phase in bipolar disorders. In spite of the fact that this strategy
      appears less adequate in bipolar disorders, these studies have demonstrated the
      existence of prodromal signs in a majority of patients. However, these features
      appear for the moment neither sufficiently characteristic, nor sufficiently
      specific to allow the construction of suitable assessment instruments, or to
      suggest precise guidelines in the management of these subjects. Also, these
      prodromal features show considerable overlap with other psychiatric disorders,
      especially attention-deficit hyperactivity disorder (ADHD) and schizophrenia
      Interestingly, a limited number of studies have looked at the number of patients
      considered in a prodromal phase of schizophrenia which later developed a bipolar
      disorder and reported substantial proportions of subjects in this case, further
      highlighting the obvious bias in favor of schizophrenia in the actual prevention
      politics. In order to identify potential candidates at a prodromal phase of
      bipolar disorders that could benefit from early intervention, studies have relied
      on both high genetic risk and symptoms at the boundary of the actual
      classification. However, even within such approach, pharmacological treatments
      have not proven obvious advantage in terms of prevention. It is suggested that
      adopting a more longitudinal vision of the disease and, given the mean age of
      onset of bipolar disorder and a fortiori of its prodromal phase, a more
      developmental perspective of individuals, could help lowering the confusion in
      this field ; Also, given the considerable overlap in prodromal features between
      different psychiatric disorders, early detection programs could benefit from
      implementing approach open to multiple diseases assessment, rather than hyper
      specialization in a specific disorder.

PMID- 20141808
TI  - AGA medical position statement on the diagnosis and management of colorectal
      neoplasia in inflammatory bowel disease.

PMID- 20141809
TI  - AGA technical review on the diagnosis and management of colorectal neoplasia in
      inflammatory bowel disease.

PMID- 20141811
TI  - Survey of United States dental schools on cementation protocols for implant crown
      restorations.
AB  - STATEMENT OF PROBLEM: With conflicting results in the literature and various
      manufacturer recommendations, it is not known what cementation protocols are
      currently being used for implant restorations in US dental schools. PURPOSE: The
      purpose of this survey was to determine what dental cementation protocols are
      taught and recommended by 62 US dental schools and postgraduate programs.
      MATERIAL AND METHODS: From February to September 2008, 96 questionnaires
      consisting of 8 questions were sent to the chairperson or director of restorative
      departments, advanced prosthodontics programs, and implant programs. The
      questionnaire asked recipients which implant manufacturers provided the products
      used at their dental schools. Additionally, recipients were queried as to the
      choice of material and techniques for abutment and restoration preparations prior
      to definitive cementation. Data were analyzed with descriptive statistics.
      RESULTS: A total of 68 (71%) surveys were returned, and 52 (84%) of the 62
      predoctoral and postgraduate programs were represented. After deleting duplicate
      responses, 31 surveys were returned from restorative department chairpersons, 29
      from advanced prosthodontic program directors, and 2 from implant program
      directors. Frequency of responses to each question was tabulated, and results are
      presented in 3 sections. For all 3 types of programs, Nobel Biocare was reported
      to be the most widely used implant system, followed by Biomet 3i, Straumann,
      Astra Tech, and Zimmer Dental systems. The most commonly used technique prior to
      definitive cementation is to airborne-particle abrade the intaglio surface of the
      restoration. Resin-modified glass ionomer is the most frequently used luting
      agent for cementing implant restorations. The 5 most commonly used materials to
      fill screw access openings are cotton pellets, composite resin, rubber-based
      material, gutta-percha, and light-polymerized provisional composite resin. Most
      predoctoral and postgraduate programs teach students to fill the screw access
      opening completely to the occlusal surface. CONCLUSIONS: There are a wide range
      of implant cementation protocols and materials used; however, some common trends
      were identified among predoctoral and postgraduate programs.

PMID- 20141812
TI  - Three-year clinical evaluation of two ceramic crown systems: a preliminary study.
AB  - STATEMENT OF PROBLEM: The clinical performance and failure mechanisms of recently
      introduced ceramic crown systems used to restore posterior teeth have not been
      adequately examined. PURPOSE: The purpose of this prospective clinical study was
      to evaluate and compare the clinical performance of 2 new ceramic crown systems
      with that of metal ceramic crowns using modified United States Public Health
      Services (USPHS) criteria. MATERIAL AND METHODS: Ninety posterior teeth requiring
      crown restorations in 48 patients were randomized into 3 equal groups (n=30) for
      which different crown systems were used: an experimental hot-pressed glass
      ceramic based on a modified lithium disilicate ceramic (IPS e.max Press), an
      alumina-coping-based ceramic (Procera AllCeram), and a metal ceramic (Simidur S 2
      veneered with IPS Classic Porcelain). The crowns were assessed over 3 years using
      the modified USPHS criteria. Crowns that developed visible cracks were sectioned
      and removed, and the surfaces were analyzed using a scanning electron microscope
      (SEM). The data were analyzed using the Kruskal-Wallis nonparametric statistical
      test, followed by the Mann-Whitney test with Bonferroni correction (alpha=.05).
      RESULTS: USPHS evaluation showed that the IPS e.max Press and metal ceramic
      crowns experienced fewer clinical changes than Procera AllCeram. Visible
      roughness, wear, and deformity were noticed in occlusal contact areas of Procera
      AllCeram crowns. SEM images showed well defined wear facets in both ceramic crown
      systems. Kruskal-Wallis tests showed a significant difference (P<.05) in Alpha
      scores among the 3 crown systems. Mann-Whitney tests showed significant
      differences among groups. CONCLUSIONS: IPS e.max Press crowns demonstrated
      clinical behavior comparable to Procera AllCeram and metal ceramic crowns, but
      the wear resistance of this crown type was superior to the Procera AllCeram
      crowns, according to modified USPHS criteria.

PMID- 20141813
TI  - Effect of varying the vertical dimension of connectors of cantilever cross-arch
      fixed dental prostheses in patients with severely reduced osseous support: a
      three-dimensional finite element analysis.
AB  - STATEMENT OF PROBLEM: Inadequate dimensioning of the connectors in a cantilever
      cross-arch fixed dental prosthesis (FDP) in perioprosthetic patients jeopardizes
      the prognosis of the restoration. PURPOSE: The purpose of this study was to
      investigate the effect of increasing the vertical dimension (VD) on the maximum
      stress developed within the connectors during the static loading of a cross-arch
      FDP extended as a 1- and 2-unit cantilever. MATERIAL AND METHODS: Six digital
      models were developed, derived from a 3-dimensional (3-D) initial model. In the
      initial model, the teeth were prepared for metal ceramic restorations and
      splinted with a cross-arch FDP, extended as a 1- or 2-unit cantilever. The VDs of
      the connectors proximal to the retaining abutment were 3, 4, or 5 mm. A 3-D
      finite element analysis (FEA) was performed. RESULTS: The VD increase, from 3 to
      4 mm and from 3 to 5 mm, of the connector distal to the retaining abutment, for
      each FDP, presented a maximum stress value decrease of approximately 25% and 48%,
      respectively. The similar VD increase of the connector mesial to the retaining
      abutment, for each FDP, resulted in relatively smaller stress changes. For the 2
      unit cantilever restoration, the stress decreases were approximately 9% and 15%,
      respectively, whereas in the 1-unit cantilever restoration, the decrease was
      about 10% for the 4-mm connector. Further increase of the VD to 5 mm did not
      relieve the peak stress. The highest stress value was measured on the 3-mm
      connector distal to the retaining abutment in the 2-unit cantilever restoration.
      Despite the VD increase, the connectors proximal to the retaining abutment still
      developed the highest stress values of all the connectors for every model.
      CONCLUSIONS: The connector with the highest risk of failure is the 3-mm connector
      distal to the retaining abutment of the 2-unit cantilever restoration. Increasing
      the vertical dimension is beneficial for the connector distal to the retaining
      abutment, while the resultant stress changes are not substantial for the
      connectors mesial to the retaining abutment. (J Prosthet Dent 2010;103:91-100).

PMID- 20141814
TI  - Comparison of cutting efficiencies between electric and air-turbine dental
      handpieces.
AB  - STATEMENT OF PROBLEM: Dentistry is gravitating toward the increased use of
      electric handpieces. The dental professional should have sufficient evidence to
      validate the switch from an air-turbine handpiece to an electric handpiece.
      However, there is little research quantifying the cutting efficiency of electric
      and air-turbine handpieces. Studies that do quantify cutting efficiency typically
      do so with only a single material. PURPOSE: The purpose of this study was to
      compare the cutting efficiency of an electric handpiece and an air-turbine
      handpiece, using various materials commonly used in dentistry. MATERIAL AND
      METHODS: Seven materials: Macor (machinable glass ceramic), silver amalgam,
      aluminum oxide, zirconium oxide, high noble metal alloy, noble metal alloy, and
      base metal alloy, were each cut with a bur 220 times; 110 times with an electric
      handpiece, and 110 times with an air-turbine handpiece. The weight difference of
      the material was calculated by subtracting the weight of the material after a cut
      from the weight of the material before the cut. The cutting efficiency was
      calculated by dividing the weight difference by the duration of the cut (g/s).
      Data were analyzed by a 2-way analysis of variance followed by Tukey's Honestly
      Significant Difference (HSD) test (alpha=.05). RESULTS: The electric handpiece
      cut more efficiently than the air-turbine handpiece (F=3098.9, P<.001). In
      particular, the high noble metal alloy, silver amalgam, and Macor were cut more
      efficiently with the electric handpiece (0.0383 +/-0.0002 g/s, 0.0260 +/-0.0002
      g/s, and 0.0122 +/-0.0002 g/s, respectively) than with the air-turbine handpiece
      (0.0125 +/-0.0002 g/s, 0.0142 +/-0.0002 g/s, and 0.008 +/-0.0002 g/s,
      respectively). CONCLUSIONS: The electric handpiece is more efficient at cutting
      various materials used in dentistry, especially machinable glass ceramic, silver
      amalgam, and high noble alloy, than the air-turbine handpiece.

PMID- 20141815
TI  - Three-body wear of resin denture teeth with and without nanofillers.
AB  - STATEMENT OF PROBLEM: The wear behavior of newly developed denture teeth with
      nanofillers may be different from teeth with other chemical formulations.
      PURPOSE: The purpose of this study was to examine the 3-body wear resistance of
      11 different commercially available resin denture teeth. MATERIAL AND METHODS:
      The materials tested were conventional (SR Orthotyp PE, Orthognath) and cross
      linked acrylic resin teeth without inorganic fillers (Premium 8, SR Postaris DCL,
      Trubyte Portrait, Artiplus), composite resin teeth with inorganic fillers (SR
      Orthosit PE, Vitapan), and composite resin teeth (experimental materials) with
      inorganic nanofillers (NC Veracia Posterior, e-Ha, Mondial). Human enamel and a
      ceramic denture tooth (Lumin Vacuum) were used as reference materials. The 3-body
      wear test was performed in a wear machine developed by the Academic Center for
      Dentistry Amsterdam (ACTA), with millet suspension acting as an abrasive medium
      (n=10, test load: 15 N, slip rate: 20%, number of cycles: 100,000). Wear was
      determined with the aid of a profilometer. Data were analyzed with the Kruskal
      Wallis test and Mann-Whitney U test using the closed testing approach
      (significance level for familywise error rate, alpha=.05). RESULTS: None of the
      acrylic and composite resin materials tested in this study demonstrated the 3
      body wear resistance of ceramic teeth or human enamel. Teeth with inorganic
      fillers demonstrated significantly lower wear values than conventional or cross
      linked acrylic resin teeth without fillers. Composite resin teeth with
      traditional fillers showed significantly lower wear than composite resin teeth
      with nanofillers. CONCLUSIONS: Denture teeth with and without inorganic fillers
      differed significantly with regard to the degree of wear generated in the ACTA
      wear simulator. The incorporation of nanofillers did not improve the wear
      resistance compared to teeth with traditional fillers.

PMID- 20141816
TI  - Retrospective study of treatment outcomes with implant-retained extraoral
      prostheses: survival rates and prosthetic complications.
AB  - STATEMENT OF PROBLEM: Implant-retained extraoral prostheses are an acceptable
      solution for patients with facial defects. However, these prostheses have a
      limited service life. Little has been reported on survival periods of implant
      retained extraoral prostheses and prosthetic complications of this treatment
      modality. PURPOSE: The purpose of this study was to estimate the survival rates
      of implant-retained extraoral prostheses and to analyze the frequency of
      prosthetic complications. MATERIAL AND METHODS: Seventy patients were treated
      with implant-retained extraoral prostheses. Each patient was examined with
      respect to the prosthesis appearance and abutment and attachment component
      complications at 6-month intervals over a period of 10 to 46 months. The Kaplan
      Meier survival estimation method was used for the first and subsequent
      prostheses. The reasons for remaking prostheses were recorded. Complications of
      the abutment and attachment components and the prostheses were recorded.
      Frequency of complications was evaluated. Data were analyzed using the Fisher
      exact test (alpha=.05). RESULTS: Thirty-two auricular, 25 orbital, and 13 nasal
      prostheses were evaluated. The Kaplan-Meier analysis revealed an estimated mean
      survival time of 14.5 months for the patients' first prostheses. The survival
      times for the first implant-retained auricular, orbital, and nasal prostheses
      were 14.1, 13.4, and 17.6 months, respectively. The survival times for the second
      implant-retained auricular, orbital, and nasal prostheses were 14.4, 15.3, and
      14.0 months, respectively. CONCLUSIONS: Implant-retained extraoral prostheses had
      limited survival rates. The primary reasons for making new prostheses were
      discoloration, tearing, and mechanical failures of the acrylic resin substructure
      or retentive elements. Common complications were the need for clip activation,
      loosening of bar screws and abutments, and loss of attachment between silicone
      and the acrylic resin substructure. (J Prosthet Dent 2010;103:118-126).

PMID- 20141817
TI  - Controlled airborne-particle abrasion of zirconia ceramic restorations.

PMID- 20141818
TI  - Chairside repair of worn or lost denture teeth using nanofilled composite resin
      bonded to the denture base.

PMID- 20141819
TI  - Learning from the noughties.

PMID- 20141820
TI  - Pandemic influenza: learning from the present.

PMID- 20141822
TI  - [Abstracts of the 10th annual meeting of the SFN (French Society of Neurology), 7
      January 2010, Paris, France].

PMID- 20141821
TI  - Experience and lessons from surveillance and studies of the 2009 pandemic in
      Europe.
AB  - Surveillance and studies in a pandemic is a complex topic including four distinct
      components: (1) early detection and investigation; (2) comprehensive early
      assessment; (3) monitoring; and (4) rapid investigation of the effectiveness and
      impact of countermeasures, including monitoring the safety of pharmaceutical
      countermeasures. In the 2009 pandemic, the prime early detection and
      investigation took place in the Americas, but Europe needed to undertake the
      other three components while remaining vigilant to new phenomenon such as the
      emergence of antiviral resistance and important viral mutation. Laboratory-based
      surveillance was essential and also integral to epidemiological and clinical
      surveillance. Early assessment was especially vital because of the many important
      strategic parameters of the pandemic that could not be anticipated (the 'known
      unknowns'). Such assessment did not need to be undertaken in every country, and
      was done by the earliest affected European countries, particularly those with
      stronger surveillance. This was more successful than requiring countries to
      forward primary data for central analysis. However, it sometimes proved difficult
      to get even those analyses from European counties, and information from Southern
      hemisphere countries and North America proved equally valuable. These analyses
      informed which public health and clinical measures were most likely to be
      successful, and were summarized in a European risk assessment that was updated
      repeatedly. The estimate of the severity of the pandemic by the World Health
      Organization (WHO), and more detailed description by the European Centre for
      Disease Prevention and Control in the risk assessment along with revised planning
      assumptions were essential, as most national European plans envisaged triggering
      more disruptive interventions in the event of a severe pandemic. Setting up new
      surveillance systems in the midst of the pandemic and getting information from
      them was generally less successful. All European countries needed to perform
      monitoring (Component 3) for the proper management of their own healthcare
      systems and other services. The information that central authorities might like
      to have for monitoring was legion, and some countries found it difficult to limit
      this to what was essential for decisions and key communications. Monitoring
      should have been tested for feasibility in influenza seasons, but also needed to
      consider what surveillance systems will change or cease to deliver during a
      pandemic. International monitoring (reporting upwards to WHO and European
      authorities) had to be kept simple as many countries found it difficult to
      provide routine information to international bodies as well as undertaking
      internal processes. Investigation of the effectiveness of countermeasures (and
      the safety of pharmaceutical countermeasures) (Component 4) is another process
      that only needs to be undertaken in some countries. Safety monitoring proved
      especially important because of concerns over the safety of vaccines and
      antivirals. It is unlikely that it will become clear whether and which public
      health measures have been successful during the pandemic itself. Piloting of
      methods of estimating influenza vaccine effectiveness (part of Component 4) in
      Europe was underway in 2008. It was concluded that for future pandemics,
      authorities should plan how they will undertake Components 2-4, resourcing them
      realistically and devising new ways of sharing analyses.

PMID- 20141823
TI  - Plagiarism.

PMID- 20141825
TI  - Editorial Board statement.

PMID- 20141828
TI  - Driving innovation: ready, set, go!
AB  - In our increasingly networked world, prizes are gaining a foothold in the race
      for innovation in science and technology. Amy Maxmen reports.

PMID- 20141829
TI  - Blocking the deadly effects of the NMDA receptor in stroke.
AB  - Excessive activation of NMDA glutamate receptors contributes to neuronal death
      after stroke. In this issue, Tu et al. (2010) demonstrate that ischemic injury
      promotes the association of death-associated protein kinase 1 with the NMDA
      receptor, thereby potentiating its activity, and show that disrupting this
      association reduces damage to the brain.

PMID- 20141830
TI  - Forever young.
AB  - Propagation of a species requires periodic cell renewal to avoid clonal
      senescence. Liu et al. (2010) now describe a new mechanism of cell renewal in
      budding yeast, in which damaged protein aggregates are transported out of the
      daughter buds along actin cables to preserve youthfulness.

PMID- 20141831
TI  - Duct tape for broken chromosomes.
AB  - A cell undergoing mitosis is presented with a potentially catastrophic situation
      when a DNA double-strand break creates a chromosome fragment that lacks
      connection to a centromere. Royou et al. (2010) now reveal that this cellular
      crisis is averted in fruit fly neuroblasts by thin chromatin tethers that hold on
      to the ends of the broken chromosomes.

PMID- 20141832
TI  - The brothers RAF.
AB  - Targeted molecular therapies for cancer treatment have shown promise, but also
      have limitations. In this issue, Heidorn et al. (2010) find that a class of
      targeted molecular therapies with clinical effectiveness against one melanoma
      subtype may have adverse clinical effects in another.

PMID- 20141833
TI  - Chaperoning histones during DNA replication and repair.
AB  - Nuclear DNA is tightly packaged into chromatin, which profoundly influences DNA
      replication, transcription, repair, and recombination. The extensive interactions
      between the basic histone proteins and acidic DNA make the nucleosomal unit of
      chromatin a highly stable entity. For the cellular machinery to access the DNA,
      the chromatin must be unwound and the DNA cleared of histone proteins.
      Conversely, the DNA has to be repackaged into chromatin afterward. This review
      focuses on the roles of the histone chaperones in assembling and disassembling
      chromatin during the processes of DNA replication and repair.

PMID- 20141834
TI  - Dietary and genetic obesity promote liver inflammation and tumorigenesis by
      enhancing IL-6 and TNF expression.
AB  - Epidemiological studies indicate that overweight and obesity are associated with
      increased cancer risk. To study how obesity augments cancer risk and development,
      we focused on hepatocellular carcinoma (HCC), the common form of liver cancer
      whose occurrence and progression are the most strongly affected by obesity among
      all cancers. We now demonstrate that either dietary or genetic obesity is a
      potent bona fide liver tumor promoter in mice. Obesity-promoted HCC development
      was dependent on enhanced production of the tumor-promoting cytokines IL-6 and
      TNF, which cause hepatic inflammation and activation of the oncogenic
      transcription factor STAT3. The chronic inflammatory response caused by obesity
      and enhanced production of IL-6 and TNF may also increase the risk of other
      cancers.

PMID- 20141835
TI  - Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through
      CRAF.
AB  - We describe a mechanism of tumorigenesis mediated by kinase-dead BRAF in the
      presence of oncogenic RAS. We show that drugs that selectively inhibit BRAF drive
      RAS-dependent BRAF binding to CRAF, CRAF activation, and MEK-ERK signaling. This
      does not occur when oncogenic BRAF is inhibited, demonstrating that BRAF
      inhibition per se does not drive pathway activation; it only occurs when BRAF is
      inhibited in the presence of oncogenic RAS. Kinase-dead BRAF mimics the effects
      of the BRAF-selective drugs and kinase-dead Braf and oncogenic Ras cooperate to
      induce melanoma in mice. Our data reveal another paradigm of BRAF-mediated
      signaling that promotes tumor progression. They highlight the importance of
      understanding pathway signaling in clinical practice and of genotyping tumors
      prior to administering BRAF-selective drugs, to identify patients who are likely
      to respond and also to identify patients who may experience adverse effects.

PMID- 20141836
TI  - DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in
      stroke.
AB  - N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate
      receptors at extrasynaptic sites that link multiple intracellular catabolic
      processes responsible for irreversible neuronal death. Here, we report that
      cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the
      NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly
      binds with the NMDA receptor NR2B C-terminal tail consisting of amino acid 1292
      1304 (NR2B(CT)). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser
      1303 and in turn enhances the NR1/NR2B receptor channel conductance. Genetic
      deletion of DAPK1 or administration of NR2B(CT) that uncouples an activated DAPK1
      from an NMDA receptor NR2B subunit in vivo in mice blocks injurious Ca(2+) influx
      through NMDA receptor channels at extrasynaptic sites and protects neurons
      against cerebral ischemic insults. Thus, DAPK1 physically and functionally
      interacts with the NMDA receptor NR2B subunit at extrasynaptic sites and this
      interaction acts as a central mediator for stroke damage.

PMID- 20141837
TI  - BubR1- and Polo-coated DNA tethers facilitate poleward segregation of acentric
      chromatids.
AB  - The mechanisms that safeguard cells against chromosomal instability (CIN) are of
      great interest, as CIN contributes to tumorigenesis. To gain insight into these
      mechanisms, we studied the behavior of cells entering mitosis with damaged
      chromosomes. We used the endonuclease I-CreI to generate acentric chromosomes in
      Drosophila larvae. While I-CreI expression produces acentric chromosomes in the
      majority of neuronal stem cells, remarkably, it has no effect on adult survival.
      Our live studies reveal that acentric chromatids segregate efficiently to
      opposite poles. The acentric chromatid poleward movement is mediated through DNA
      tethers decorated with BubR1, Polo, INCENP, and Aurora-B. Reduced BubR1 or Polo
      function results in abnormal segregation of acentric chromatids, a decrease in
      acentric chromosome tethering, and a great reduction in adult survival. We
      propose that BubR1 and Polo facilitate the accurate segregation of acentric
      chromatids by maintaining the integrity of the tethers that connect acentric
      chromosomes to their centric partners.

PMID- 20141838
TI  - Structural and energetic mechanisms of cooperative autoinhibition and activation
      of Vav1.
AB  - Vav proteins are guanine nucleotide exchange factors (GEFs) for Rho family
      GTPases. They control processes including T cell activation, phagocytosis, and
      migration of normal and transformed cells. We report the structure and
      biophysical and cellular analyses of the five-domain autoinhibitory element of
      Vav1. The catalytic Dbl homology (DH) domain of Vav1 is controlled by two
      energetically coupled processes. The DH active site is directly, but weakly,
      inhibited by a helix from the adjacent Acidic domain. This core interaction is
      strengthened 10-fold by contacts of the calponin homology (CH) domain with the
      Acidic, pleckstrin homology, and DH domains. This construction enables efficient,
      stepwise relief of autoinhibition: initial phosphorylation events disrupt the
      modulatory CH contacts, facilitating phosphorylation of the inhibitory helix and
      consequent GEF activation. Our findings illustrate how the opposing requirements
      of strong suppression of activity and rapid kinetics of activation can be
      achieved in multidomain systems.

PMID- 20141839
TI  - The polarisome is required for segregation and retrograde transport of protein
      aggregates.
AB  - The paradigm sirtuin, Sir2p, of budding yeast is required for establishing
      cellular age asymmetry, which includes the retention of damaged and aggregated
      proteins in mother cells. By establishing the global genetic interaction network
      of SIR2 we identified the polarisome, the formin Bni1p, and myosin motor protein
      Myo2p as essential components of the machinery segregating protein aggregates
      during mitotic cytokinesis. Moreover, we found that daughter cells can clear
      themselves of damage by a polarisome- and tropomyosin-dependent polarized flow of
      aggregates into the mother cell compartment. The role of Sir2p in cytoskeletal
      functions and polarity is linked to the CCT chaperonin in sir2Delta cells being
      compromised in folding actin. We discuss the findings in view of recent models
      hypothesizing that polarity may have evolved to avoid clonal senescence by
      establishing an aging (soma-like) and rejuvenated (germ-like) lineage.

PMID- 20141840
TI  - Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote
      epithelial cancer development.
AB  - It is established that tumor cell-derived VEGF acts on endothelial cells to
      promote angiogenesis and tumor growth. Here, we demonstrate that in K5-SOS
      dependent mouse skin tumors, autocrine VEGF is required for tumor cell
      proliferation in a cell-autonomous and angiogenesis-independent manner. VEGF is
      upregulated in SOS-expressing tumors, and its deletion in epidermal cells delays
      tumorigenesis by suppressing angiogenesis and tumor cell proliferation. Epidermis
      specific Flt1 deletion also impairs tumorigenesis and proliferation.
      Surprisingly, complete tumor inhibition occurs in the absence of VEGF in EGFR
      mutant mice, demonstrating that VEGFR and EGFR synergize in neoplastic cells to
      promote tumor growth. Mechanistically, K5-SOS upregulates VEGF, Flt1, and
      Neuropilin-1 in an Erk-dependent manner, thereby activating an autocrine
      proliferation loop, whereas EGFR prevents tumor cells from apoptosis. Moreover,
      Flt1 is upregulated in human SCC, and its inhibition in SCC cells impairs
      proliferation. Thus, in addition to regulating angiogenesis, VEGF has to be
      considered as a potent growth factor for epidermal tumors.

PMID- 20141842
TI  - SnapShot: Bacterial appendages II.

PMID- 20141841
TI  - The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha.
AB  - SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases
      with various roles in metabolism, stress resistance, and life span. SIRT6
      deficient mice develop normally but succumb to a lethal hypoglycemia early in
      life; however, the mechanism underlying this hypoglycemia remained unclear. Here,
      we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the
      expression of multiple glycolytic genes. Specifically, SIRT6 appears to function
      as a corepressor of the transcription factor Hif1alpha, a critical regulator of
      nutrient stress responses. Consistent with this notion, SIRT6-deficient cells
      exhibit increased Hif1alpha activity and show increased glucose uptake with
      upregulation of glycolysis and diminished mitochondrial respiration. Our studies
      uncover a role for the chromatin factor SIRT6 as a master regulator of glucose
      homeostasis and may provide the basis for novel therapeutic approaches against
      metabolic diseases, such as diabetes and obesity.

PMID- 20141853
TI  - Retinal examination and photography are safe...is anyone surprised?

PMID- 20141854
TI  - Glaucoma clinical trials.

PMID- 20141855
TI  - Bilateral VI nerve injury.

PMID- 20141856
TI  - IgG4-related dacryoadenitis.

PMID- 20141857
TI  - Implantable collamer lens dislocation.

PMID- 20141858
TI  - IOL power calculations.

PMID- 20141860
TI  - Tuberculous uveitis.

PMID- 20141862
TI  - Recurrent corneal erosions.

PMID- 20141864
TI  - Histologic safety margins of periocular BCC.

PMID- 20141866
TI  - H1N1 pandemic and ophthalmology.

PMID- 20141867
TI  - [Assessment of HbA1c in capillary blood compared to venous blood].

PMID- 20141871
TI  - A safety assessment of non-cyclic alcohols with unsaturated branched chain when
      used as fragrance ingredients: the RIFM expert panel.

PMID- 20141872
TI  - Fragrance material review on 2-hexadecen-1-ol, 3,7,11,15-tetramethyl.
AB  - A toxicologic and dermatologic review of 2-hexadecen-1-ol, 3,7,11,15-tetramethyl
      when used as a fragrance ingredient is presented.

PMID- 20141873
TI  - Fragrance material review on 7-nonen-2-ol, 4,8-dimethyl-.
AB  - A toxicologic and dermatologic review of 7-nonen-2-ol, 4,8-dimethyl- when used as
      a fragrance ingredient is presented.

PMID- 20141874
TI  - Fragrance material review on 6-ethyl-3-methyloct-6-en-1-ol.
AB  - A toxicologic and dermatologic review of 6-ethyl-3-methyloct-6-en-1-ol when used
      as a fragrance ingredient is presented.

PMID- 20141875
TI  - Addendum to Fragrance material review on Nerolidol (isomer unspecified).
AB  - An addendum to the toxicologic and dermatologic review of Nerolidol (isomer
      unspecified) when used as a fragrance ingredient is presented.

PMID- 20141876
TI  - Fragrance material review on 7-octen-2-ol, 2-methyl-6-methylene-, dihydro
      derivative.
AB  - A toxicologic and dermatologic review of 7-octen-2-ol, 2-methyl-6-methylene-,
      dihydro derivative when used as a fragrance ingredient is presented.

PMID- 20141877
TI  - Fragrance material review on 3,7-dimethyl-1,6-nonadien-3-ol.
AB  - A toxicologic and dermatologic review of 3,7-dimethyl-1,6-nonadien-3-ol when used
      as a fragrance ingredient is presented.

PMID- 20141878
TI  - Fragrance material review on methylheptenol.
AB  - A toxicologic and dermatologic review of methylheptenol when used as a fragrance
      ingredient is presented.

PMID- 20141879
TI  - Fragrance material review on phytol.
AB  - A toxicological and dermatologic review of phytol when used as a fragrance
      ingredient is presented.

PMID- 20141880
TI  - Fragrance material review on 3-methyl-2-buten-1-ol.
AB  - A toxicologic and dermatologic review of 3-methyl-2-buten-1-ol when used as a
      fragrance ingredient is presented.

PMID- 20141881
TI  - Fragrance material review on dihydromyrcenol.
AB  - A toxicologic and dermatologic review of dihydromyrcenol when used as a fragrance
      ingredient is presented.

PMID- 20141882
TI  - Fragrance material review on isophytol.
AB  - A toxicologic and dermatologic review of isophytol when used as a fragrance
      ingredient is presented.

PMID- 20141883
TI  - Fragrance material review on 2-methyl-2-hepten-6-ol.
AB  - A toxicologic and dermatologic review of 2-methyl-2-hepten-6-ol when used as a
      fragrance ingredient is presented.

PMID- 20141884
TI  - Fragrance material review on (Z)-2-penten-1-ol.
AB  - A toxicologic and dermatologic review of (Z)-2-penten-1-ol when used as a
      fragrance ingredient is presented.

PMID- 20141885
TI  - Fragrance material review on 2,6,10-trimethylundeca-5,9-dienol.
AB  - A toxicologic and dermatologic review of 2,6,10-trimethylundeca-5,9-dienol when
      used as a fragrance ingredient is presented.

PMID- 20141886
TI  - Fragrance material review on 3,5,6,6-tetramethyl-4-methyleneheptan-2-ol.
AB  - A toxicologic and dermatologic review of 3,5,6,6-tetramethyl-4-methyleneheptan-2
      ol when used as a fragrance ingredient is presented.

PMID- 20141887
TI  - Fragrance material review on (2E,6Z)-nona-2,6-dien-1-ol.
AB  - A toxicologic and dermatologic review of (2E,6Z)-nona-2,6-dien-1-ol when used as
      a fragrance ingredient is presented.

PMID- 20141888
TI  - Fragrance material review on 4-methyl-3-decen-5-ol.
AB  - A toxicologic and dermatologic review of 4-methyl-3-decen-5-ol when used as a
      fragrance ingredient is presented.

PMID- 20141889
TI  - Fragrance material review on 2-methyl-3-buten-2-ol.
AB  - A toxicologic and dermatologic review of 2-methyl-3-buten-2-ol when used as a
      fragrance ingredient is presented.

PMID- 20141890
TI  - Rate of infection after carpal tunnel release surgery and effect of antibiotic
      prophylaxis.
AB  - PURPOSE: To determine the rate of postoperative wound infection and the
      association with prophylactic antibiotic use in uncomplicated carpal tunnel
      release surgery. METHODS: We performed a multicenter, retrospective review of all
      the carpal tunnel release procedures performed between January 1, 2005, and
      August 30, 2007. Data reviewed included the use of prophylactic antibiotics,
      diabetic status, and the occurrence of postoperative wound infection. We
      determined the overall antibiotic usage rate and analyzed the correlation between
      antibiotic use and the development of postoperative wound infection. RESULTS: The
      rate of surgical site infections in the 3003 patients who underwent carpal tunnel
      release surgery (group A) was 11. Antibiotic usage data were available for 2336
      patients (group B). Six patients without prophylactic antibiotics had infection,
      as did 5 patients with prophylactic antibiotics. This difference was not
      statistically significant. Of the 11 surgical site infections, 4 were deep
      (organ/space) and 7 superficial (incisional). The number of patients with
      diabetes in the overall study population was 546, 3 of whom had infections. This
      was not statistically different from the nondiabetic population infection rate (8
      patients). CONCLUSIONS: The overall infection rate after carpal tunnel release
      surgery is low. In addition, the deep (organ/space) infection rate is much lower
      than previously reported. Antibiotic use did not decrease the risk of infection
      in this study population, including patients with diabetes. The routine use of
      antibiotic prophylaxis in carpal tunnel release surgery is not indicated.
      Surgeons should carefully consider the risks and benefits of routinely using
      prophylactic antibiotics in carpal tunnel release surgery. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic III.

PMID- 20141891
TI  - Intra- and inter-examiner variability in performing Tinel's test.
AB  - PURPOSE: The Tinel sign was adopted in the early 1950s to detect sites of nerve
      compression. There have been few attempts to standardize how one elicits Tinel's
      sign. The goal of this study was to evaluate intra- and inter-examiner
      variability in the force generated using different techniques to elicit Tinel's
      sign. METHODS: Nine clinicians, consisting of 3 experienced hand and peripheral
      nerve surgeons, 3 junior hand and peripheral nerve surgeons, and 3 surgeons in
      training were included in the study. Three different Tinel-type maneuvers were
      evaluated: (1) striking the load cell using the dominant middle finger only
      ("single-finger strike"), (2) using the dominant index and middle finger together
      ("double-finger strike"), and (3) preloading with the nondominant thumb and then
      striking the thumb with the dominant middle finger ("preload"). Test subjects
      were instructed to use their customary range of force during the testing. Each
      subject performed 3 sets of 5 strikes per technique. RESULTS: There was a
      significant difference in nearly all subjects between the range of force
      generated with single- or double-finger techniques and preload technique. There
      was also a difference in nearly all subjects when comparing the range of forces
      using the single-and double-finger techniques. In addition, there were large
      differences in the range of forces produced by the examiners for each technique.
      CONCLUSIONS: There is no standardization for eliciting the Tinel sign. This study
      demonstrates considerable intra- and inter-examiner differences in the range of
      forces generated by the different Tinel's techniques that are used in clinical
      practice. This variability might explain clinical differences between examiners
      in the ability to obtain a Tinel sign in a patient and might explain the
      inconsistency of sensitivity and specificity reported for Tinel's sign. Further
      research on standardization is needed, and future study protocols using Tinel's
      sign should take these findings into account.

PMID- 20141892
TI  - Single-incision extensile volar approach to the distal radius and concurrent
      carpal tunnel release: cadaveric study.
AB  - PURPOSE: To determine whether a single-incision extensile approach to the distal
      radius used for open reduction internal fixation and a concomitant radial sided
      carpal tunnel (CT) release safely and effectively decompresses the carpal tunnel.
      METHODS: Five pairs of cadaveric forearms were mounted to a tabletop with a cable
      pulley system attached to the long finger. Each paired specimen was randomized to
      volar plating via either the flexor carpi radialis approach (control group) or
      the extensile volar exposure (combined flexor carpi radialis and radial-sided
      carpal tunnel release). Before and after the respective exposure and plating,
      increased CT pressures were created with 2.27, 4.54, and 6.81 kg of distraction.
      We used a paired t-test to compare the change in CT pressure at each level of
      distraction before and after intervention for the 2 groups, with significance set
      at p </= .05. A dissection of each exposure was performed with attention given to
      the radial aspect of the transverse carpal ligament (TCL) and any possible
      iatrogenic injuries. RESULTS: Carpal tunnel pressure increased with increasing
      distraction. We noted a statistically significant reduction in CT pressure after
      the extensile exposure and plating with 4.54 (p = .023) and 6.81 (p < .001) kg of
      distraction, respectively. No significant reduction in mean CT pressure for the
      control group specimens occurred at any level of distraction force. The average
      length of the radial TCL was 22 mm (range, 18-31 mm); the average distance
      between the recurrent motor branch and distal TCL was 11 mm (range, 8-15 mm). No
      iatrogenic tendon or nerve injury occurred with the extensile volar exposure.
      CONCLUSIONS: Carpal tunnel pressure is safely reduced and the distal radius is
      adequately exposed for fixation with the extensile volar approach.

PMID- 20141893
TI  - Delayed-onset ulnar neuropathy at the wrist associated with distal radioulnar
      joint arthritis after radius malunion: report of two cases.
AB  - Although ulnar neuropathy can occur at the wrist in association with distal
      radius fractures, few late-onset cases have been reported. The authors describe 2
      cases of delayed-onset ulnar neuropathy at the wrist, which developed 12 and 30
      years after sustaining a conservatively treated distal radius fracture. During
      late neurolysis, both patients were found to have a perforation in the volar
      wrist capsule and synovitis and arthritis in the distal radioulnar joint.

PMID- 20141894
TI  - Conformational changes in the carpus during finger trap distraction.
AB  - PURPOSE: Wrist distraction is a common treatment maneuver used clinically for the
      reduction of distal radial fractures and midcarpal dislocations. Wrist
      distraction is also required during wrist arthroscopy to access the radiocarpal
      joint and has been used as a test for scapholunate ligament injury. However, the
      effect of a distraction load on the normal wrist has not been well studied. The
      purpose of this study was to measure the three-dimensional conformational changes
      of the carpal bones in the normal wrist as a result of a static distractive load.
      METHODS: Using computed tomography, the dominant wrists of 14 healthy volunteers
      were scanned at rest and during application of 98 N of distraction. Load was
      applied using finger traps, and volunteers were encouraged to relax their forearm
      muscles and to allow distraction of the wrist. The motions of the bones in the
      wrist were tracked between the unloaded and loaded trial using markerless bone
      registration. The average displacement vector of each bone relative to the radius
      was calculated, as were the interbone distances for 20 bone-bone interactions.
      Joint separation was estimated at the radiocarpal, midcarpal, and carpometacarpal
      joints in the direction of loading using the radius, lunate, capitate, and third
      metacarpal. RESULTS: With loading, the distance between the radius and third
      metacarpal increased an average of 3.3 mm +/- 3.1 in the direction of loading.
      This separation was primarily in the axial direction at the radiocarpal (1.0 mm
      +/- 1.0) and midcarpal (2.0 mm +/- 1.7) joints. There were minimal changes in the
      transverse direction within the distal row, although the proximal row narrowed by
      0.98 mm +/- 0.7. Distraction between the radius and scaphoid (2.5 mm +/- 2.2) was
      2.4 times greater than that between the radius and lunate (1.0 mm +/- 1.0).
      CONCLUSIONS: Carpal distraction has a significant (p < .01) effect on the
      conformation of the carpus, especially at the radiocarpal and midcarpal joints.
      In the normal wrist, external traction causes twice as much distraction at the
      lunocapitate joint than at the radiolunate joint.

PMID- 20141895
TI  - Gender differences in carpal height ratio in a taiwanese population.
AB  - PURPOSE: To discover whether there is a significant difference in carpal height
      ratio (CHR) between men and women aged 20 to 50 years. METHODS: We
      retrospectively reviewed 261 cases of normal plain wrist radiographs and measured
      the CHR using the Picture Achieving and Communication System. Each case was then
      stratified by gender and age (20-29, 30-39, and 40-50 y). RESULTS: The mean CHR
      was 0.52 +/- 0.03 for men (range, 0.43-0.59), 0.50 +/- 0.03 for women (range,
      0.43-0.57), and 0.51 +/- 0.03 for the total population (range, 0.43-0.59). The
      difference in CHR between men and women was statistically significant (p<.01).
      However, there was no significant difference (p=.13) among age groups in either
      men or women. CONCLUSIONS: We recommend using gender-specific norms (ie, 0.52 +/-
      0.03 for men and 0.50 +/- 0.03 for women, respectively) for CHR. Without gender
      specification, a subtle abnormality may be overlooked in men, and there may be an
      overdiagnosis of carpal disorder in women. Further investigations are needed to
      look into possible racial differences, because our study is based on a
      homogeneous ethnic Chinese population.

PMID- 20141896
TI  - Effects of distal radius bone graft harvest on the axial compressive strength of
      the radius.
AB  - PURPOSE: The effect of metaphyseal cancellous bone graft harvest on distal radius
      compressive strength is unknown. The purpose of this study was to analyze, in a
      cadaveric model, changes in distal radius axial compressive strength after distal
      radius metaphyseal cancellous bone graft harvest. METHODS: We randomized 15
      matched pairs of cadaveric radiuses into 2 groups. In group I, a target harvest
      of 25% of the total metaphyseal cancellous bone volume was attempted through a
      standardized oval cortical window. In group II, a target of 50% harvest was
      attempted. The study specimens and their matched controls from the contralateral
      side were loaded to failure in axial compression. The amount of bone graft
      harvested was calculated. The resulting ultimate loads to failure were measured,
      then expressed as ultimate stress (millipascals--MPa). We analyzed data for the 2
      groups and the matched controls using paired Student's t-tests. RESULTS: A
      smaller amount of bone was harvested than anticipated in both groups. The final
      average distal radius bone graft harvest for group I was 10%, and for group II,
      22.5%. Group I had no statistically significant difference in ultimate stress
      compared with the contralateral specimens that acted as matched controls (p =
      .273). Group II had a statistically significant decrease in ultimate stress
      values compared with matched controls (p = .002). The ultimate stress of group I
      averaged 92.67% of its matched control, whereas the ultimate stress of group II
      was 74.8% of its matched control (p = .027). CONCLUSIONS: A significant decrease
      in distal radius ultimate stress occurs when approximately 23% of the metaphyseal
      cancellous bone is removed through a standardized oval cortical window. When the
      distal radius is chosen as the bone graft harvest site, we recommend harvest of
      less than 25% of the total available distal radius metaphyseal cancellous bone to
      prevent alteration of the load characteristics of the bone.

PMID- 20141897
TI  - Tardy palsy of descending branch of posterior interosseous nerve: sequela to
      plate osteosynthesis of forearm bones.
AB  - We report a case of tardy paralysis of the descending branch of the posterior
      interosseous nerve as a consequence of plate osteosynthesis for fracture of both
      bone forearms. The patient had been operated on 23 years earlier and palsy
      occurred after a gap of 19 years. The most probable antecedent cause of the palsy
      was the use of a high-profile implant. The patient was treated by removal of the
      plate and tendon transfer.

PMID- 20141898
TI  - Functional outcomes after upper extremity surgery for cerebral palsy: comparison
      of high and low manual ability classification system levels.
AB  - PURPOSE: The heterogeneity of cerebral palsy makes interpretation and prediction
      of outcome after upper extremity surgery difficult. We hypothesized that the
      outcome of upper extremity surgery for cerebral palsy is related to the Manual
      Ability Classification System (MACS) level. METHODS: We reviewed 27 patients with
      a mean age of 22 years, who underwent upper extremity surgery for spastic
      cerebral palsy at a mean follow-up of 29 months. Patients were classified into 5
      MACS levels using a standardized questionnaire completed by their primary
      caregivers. Preoperatively and at most recent follow-up visits, patients were
      assessed using the House scale and patient-reported functional outcomes on a 5
      point scale. We compared the outcomes of patients with high (I-II, independence
      in daily activities) and low (III-V, dependence in daily activities) MACS levels.
      RESULTS: The overall mean House scale improved from 2.9 to 4.6 postoperatively
      (p<.001), dressing ability from 3.7 to 4.2 (p=.005), hygiene from 4.2 to 4.9
      (p=.005), and appearance from 2.4 to 4.2 (p<.001). A total of 13 patients had a
      high MACS level (7 had I and 6 had II) and 14 had a low MACS level (8 had III, 6
      had IV, and none had V). The high-MACS group had a greater improvement according
      to the House scale (p=.009) and the low-MACS group had a larger improvement in
      hygiene status (p=.043). There were no differences in the amount of improvement
      in dressing ability (p=.169) and appearance (p=.765). Overall satisfaction with
      surgery was higher for the high-MACS group (p=.038). CONCLUSIONS: The high-MACS
      group had a greater improvement in rating according to the House scale and higher
      satisfaction than the low-MACS group after upper extremity surgery for cerebral
      palsy in our small number of patients. This study suggests that the MACS level
      can be used to predict upper extremity surgery outcomes for cerebral palsy. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 20141899
TI  - Partial hand preservation for large soft tissue sarcomas of the hand.
AB  - PURPOSE: Hand amputations cause marked functional loss for patients. In patients
      with large soft tissue sarcomas of the hand, partial hand preservation is
      extremely challenging for surgeons attempting a complete resection of the tumor
      with negative resection margins. We conducted this review to examine the
      oncologic outcome, including local recurrence rate and patient overall survival,
      and functional outcome after resections for large soft tissue sarcomas with
      partial hand preservation. METHODS: We performed a retrospective review of all
      patients with soft tissue sarcomas of the hand treated at our institution from
      1995 to 2007. We identified 8 patients who had tumors at least 5 cm in maximum
      dimension and had tumor resection with partial hand preservation. The mean age at
      the time of surgery was 49 years (range, 10-80 years). Two patients had
      myxofibrosarcoma, 2 patients had synovial sarcoma, 2 patients had malignant
      fibrous histiocytoma, 1 patient had a malignant peripheral nerve sheath tumor,
      and 1 patient had a liposarcoma. Two patients had low-grade tumors, and 6
      patients had high-grade tumors. Two patients had American Joint Committee on
      Cancer stage 1b tumors, and 6 patients had American Joint Committee on Cancer
      stage 3 tumors. No patients had distant metastases at the time of surgery. Hand
      function was evaluated using Musculoskeletal Tumor Society criteria. RESULTS: Of
      the 8 patients, 1 died of distant metastatic disease, 1 developed local tumor
      recurrence and is alive with locally recurrent disease, and the other 6 patients
      are completely disease-free. The mean Musculoskeletal Tumor Society score was 26
      (range, 19-29), with the 2 patients who had received double-ray amputations
      having the lower scores (19 and 24). CONCLUSIONS: Partial hand preservation is
      possible in selected patients with large soft tissue sarcomas of the hand,
      obtaining low local recurrence rates, good overall survival, and good functional
      outcome. However, all effort should be made to achieve negative resection
      margins. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 20141900
TI  - Treatment of distal diaphyseal humerus fractures.

PMID- 20141901
TI  - Magnetic resonance imaging for ulnar wrist pain.

PMID- 20141902
TI  - Radial artery perforator flap.
AB  - Soft tissue defects in the hand and wrist can be challenging problems for the
      hand surgeon. The retrograde radial forearm fasciocutaneous flap has emerged in
      recent years as the workhorse flap to cover many hand and wrist defects. However,
      recognition of the intrinsic limitations of this flap has led to the development
      of other alternative flaps to provide soft tissue coverage for this region. The
      radial artery perforator flap has many of the benefits of the radial forearm flap
      but minimizes the disadvantages, such as the need to sacrifice the radial artery,
      color and bulk mismatch of the flap and recipient tissues, and donor site
      appearance. In this article, we will review the indications for using the radial
      artery perforator flap to cover hand and wrist soft tissue defects. We will
      discuss the surgical anatomy, indications, operating technique, rehabilitation
      protocol, potential complications, and pearls and pitfalls for use of this flap
      for upper-extremity defects.

PMID- 20141903
TI  - Surgical technique of harvesting vascularized superficial radial nerve graft.
AB  - We describe our surgical technique for harvesting the free vascularized
      superficial radial nerve graft based on the radial artery and its venae
      comitantes. Anatomy and preoperative preparation are also presented, as well as
      the indications and some contraindications.

PMID- 20141904
TI  - Perioperative insulin dosing in diabetic patients undergoing outpatient upper
      extremity surgery.

PMID- 20141905
TI  - Current concepts in the management of brachial plexus birth palsy.
AB  - Brachial plexus birth palsy, although rare, may result in substantial and chronic
      impairment. Physiotherapy, microsurgical nerve reconstruction, secondary joint
      corrections, and muscle transpositions are employed to help the child maximize
      function in the affected upper extremity. Many present controversies regarding
      natural history, microsurgical treatment, and secondary shoulder reconstructive
      surgery remain unresolved in infants with brachial plexus birth palsies. Recent
      literature has enhanced our understanding of the pathoanatomy and natural history
      of the injury as well as the surgical indications, expected outcomes, and
      complications; this literature has led to improved care of these patients. Based
      on the present evidence, recommendations for both microsurgery and shoulder
      reconstruction with tendon transfer and arthroscopic and open reductions are
      presented.

PMID- 20141906
TI  - Nerve transfers: indications, techniques, and outcomes.
AB  - This article provides an update of the current strategies of motor and sensory
      nerve transfers for peripheral nerve lesions of the upper extremity. Indications,
      techniques, and outcomes are summarized for both well-established transfers used
      in the management of proximal and brachial plexus injuries as well as those more
      recently developed for more distal and isolated nerve injuries in the forearm and
      hand.

PMID- 20141907
TI  - [Intrauterine death and twin pregnancy].
AB  - Single fetal death in a twin pregnancy occurs in 5% of all twin pregnancies.
      Following single-twin death the perinatal mortality and the morbidity for the
      surviving twin is increased mainly in monochorionic pregnancy. These may include
      co twin death and survival impairment in the surviving co-twin in about 12% and
      18% of cases respectively in case of monochorionic pregnancy and 4% and 1% in
      case of dichorionic pregnancy. The odds of intrauterine death of the co-twin and
      neurological abnormality among survivors is six and four times higher in
      monochorionic compared with dichorionic pregnancies due to shared placental
      circulation. The risk of preterm delivery is about 50% occurring 3 or 4 weeks
      after the death. No specific exam should be done in case of intrauterine death in
      dichorionic pregnancy whereas ultrasound and MRI should be realised to detect
      specific cerebral anomalies within 3-4 weeks of the death of the co-twin. For all
      death in utero occurring in twin pregnancy, a psychological care must be offered.

PMID- 20141908
TI  - [What type of delivery for twins?].
AB  - OBJECTIVES: To determine if perinatal and neonatal morbidity and mortality is
      improved by a planned caesarean section for twins before and at term. METHODS: A
      systematic search was conducted in Medline between May 2001 and December 2008.
      Randomised controlled studies and meta-analysis were researched at first.
      RESULTS: There is no evidence to support a policy of planned caesarean section or
      vaginal delivery for twins before term or at term whatever the presentation of
      the first twin. There is also no evidence to support a policy of caesarean
      section or vaginal delivery for a patient with a history of prior caesarean
      section. Vaginal delivery must be made in the presence of an obstetrician, an
      anaesthesiologist, and a paediatrician in a level maternity adapted to the risks
      of the future newborn. CONCLUSION: Otherwise, there is no evidence to support a
      policy of planned caesarean delivery for twins but the type of delivery has to be
      decided with the informed patient.

PMID- 20141909
TI  - [Management of second twin delivery].
AB  - OBJECTIVE: To determine the optimal mode of delivery of the second twin according
      to his presentation. METHODS: The PubMed data base has been consulted. RESULTS:
      Considering longer intertwin intervals are correlated with poorer umbilical
      artery blood gas results and are associated with greater rates of cesareans for
      the second twin after vaginal birth of the first twin and increased neonatal
      morbidity of the second twin, second twin delivery should be actively managed for
      reducing this interval (EL3). In case of non cephalic presentation of the second
      twin, immediate total breech extraction, after internal version in case of
      transverse lie, could be associated with lower rates of cesareans for the second
      twin (EL3). In these situations, external version might be deleterious (EL3). In
      case of cephalic presentation above a 0 station, and if the obstetrical team is
      trained in obstetrical maneuvers, internal version followed by immediate total
      breech extraction could be preferred to the association of maternal pushing
      efforts, oxytocin infusion and artificial rupture of the membranes, because this
      first strategy might be associated with less cesareans for the second twin (EL4).
      In case of cephalic presentation at or below a 0 station, management of second
      twin delivery should consist in the association of maternal pushing efforts,
      oxytocin infusion and artificial rupture of the membranes (EL3). All the
      obstetrical maneuvers for second twin delivery should be performed in first
      intent with intact membranes (EL5). CONCLUSIONS: Second twin delivery should be
      actively managed and largely depends on the knowledge of specific obstetrical
      maneuvers. Training residents to these maneuvers remains a priority.

PMID- 20141910
TI  - [Social and economics aspects of multiple births].
AB  - Twin pregnancy is not a simple one, firstly because, of course, not only are
      there of course 2 foetus which make special medical care necessary, but also
      because a birth of twins has social, economic and psychological impacts under
      families, peculiar to this kind of pregnancy (high rank pregnancies are not
      tackled in these recommendations - or such a little thing - but the whole
      description for twin pregnancy is valid or even increased for triplets or more
      pregnancies). It has been found useful to inform the medical profession of these
      specificities. These pages are the expression of a presence of listening and of
      demands since more than 30 years beside French multiple births families. The
      setting up in France of recommendations of clinical practices for the follow up
      care of twin pregnancies has been a demand of multiple births parents for a long
      time. They hope of these recommendations will result in optimal care of the
      specific risks of twin pregnancies therefore a more favourable prognosis for
      future twins and thus avoid as much as possible an overload of the impact on the
      family unit.

PMID- 20141911
TI  - [Introduction to the diagnosis and management of adult female urinary
      incontinence].

PMID- 20141912
TI  - [Methods and organization].

PMID- 20141913
TI  - [Epidemiology and definition of female urinary incontinence].
AB  - Urinary incontinence is the complaint of any involuntary leakage of urine. Among
      women in the general population, the most common types are stress urinary
      incontinence, urge urinary incontinence and mixed urinary incontinence (EL4).
      Urinary incontinence is common and affects 25% to 45% of the women in the general
      population. The prevalence of incontinence increases with age up to the age of 65
      (EL2). Many risk factors have been proposed for urinary incontinence. However,
      those for which the definitive evidence for a causal link and an effective risk
      reduction intervention are available are only a few. The best studied factor is
      overweight, clearly associated with incontinence and which reduction decreases by
      approximately 50% urinary incontinence episodes. Genital prolapse is associated
      with urinary incontinence and prolapse surgery reduces incontinence. Data
      concerning several classical risk factors for incontinence such as
      hypoestrogenism and vaginal delivery are contradictory (EL1). Urinary
      incontinence affects health with consequences such as dermatologic complications
      (skin maceration and ulcers) and falls. Urinary incontinence reduces the quality
      of life and generates high costs for affected individuals and in terms of public
      health (EL1).

PMID- 20141914
TI  - [Clinical diagnosis and evaluation of female urinary incontinence].
AB  - OBJECTIVES: To establish recommendations on relevant methods for diagnosis and
      evaluation of female urinary incontinence (UI). MATERIAL AND METHODS: A
      literature review on Medline referenced papers between 1980 and 2009 was
      performed. Furthermore, the present recommendations derived form these of the
      SIFUD-PP published in 2001 and of the IUGA published in 2008. RESULTS: Patient
      interview allow to evocate the diagnosis of UI and to precise the type. The cough
      stress test is simple, reliable and reproducible for the diagnosis of stress
      urinary incontinence (SUI). An angle > 30 degrees during the Q-Tip test define
      uretral hypermobility. The voiding diary is a simple, non-invasive and cost
      effective method which has to be proposed before urodynamics. The pad test allows
      an objective evaluation of UI severity. The use of at least one validated
      questionnaire for symptoms and quality of life is recommended. CONCLUSION:
      Clinical diagnosis and evaluation of female urinary incontinence is based on
      patient interview, cough stress test, clinical evaluation of uretral mobility (Q
      Tip test), voiding diary, pad test and validated questionnaires for symptoms and
      quality of life.

PMID- 20141915
TI  - [Urodynamic examination in the investigation of non neurological female urinary
      incontinence].
AB  - BACKGROUND: Female urinary incontinence raises various physiopathological
      mechanisms which can be investigated by urodynamics. The aim of this work is to
      specify the validity and the relevance of the various urodynamic parameters used
      in clinical practice. METHODS: A bibliographical research was realized on the
      basis of Medline data from original articles dealing with the incontinence in the
      absence of genital prolapse. CONCLUSIONS: Urodynamic examination has to contain
      uroflowmetry, post void residual, filling cystometry with detrusor pressure
      measurements during micturition, urethral pressure profile with maximal urethral
      closure pressure (MUCP) and Valsalva leak point pressure (VLPP). A urodynamic
      examination is not necessary before conservative treatment of urinary
      incontinence in the female. A complete urodynamic examination is recommended
      before any decision of surgical correction of urinary incontinence and in case of
      surgical failure.

PMID- 20141916
TI  - [Conservative treatment of female stress urinary incontinence].
AB  - OBJECTIVES: To synthethise evidence based results related to non surgical
      management for urinary incontinence in women. MATERIALS AND METHODS: Electronic
      search in Pubmed, Cinahl, Cochrane Library, National Library for Health. RESULTS:
      There were 72 randomized control studies and 8 reviews from the Cochrane Library.
      CONCLUSION: Moderate to high levels of evidence suggest that pelvic muscle
      training and bladder training may resolve urinary incontinence in women. A weight
      loss program from obesity state improve urinary continence. The effects of
      electrical stimulation of pelvic floor, oestrogene therapy were inconstant or
      inhomogeneous. Duloxetine may improve continence and quality of life but it's
      range in therapeutic algorithm is still to be defined.

PMID- 20141917
TI  - [Diagnosis of chorionicity].
AB  - INTRODUCTION: The recognition of mono- and dichorionic twins is highly important
      and should be performed as early as possible during the pregnancy. This is
      justified by major differences between these two types of pregnancies for fetal
      mortality, morbidity, features of the complications, and appropriate follow up is
      required. OBJECTIVES: To determine the modalities for the diagnosis of
      chorionicity. METHODS: Articles were searched using PubMed, Embase and Cochrane
      library. RESULTS: The diagnosis of chorionicity is appropriately made by the
      ultrasound examination. Before 10 weeks of gestation, the appearance and count of
      the gestational sacs is the best method (ELNP2). During first trimester
      ultrasound examination at around 12 weeks of gestation, the lambda sign is the
      most relevant sonographic sign (ELNP2). The diagnosis of chorionicity should be
      mentioned in the report of the first trimester scan. The diagnosis of
      chorionicity performed at first trimester is the reference for the rest of the
      pregnancy. Indeed, further determination of the chorionicity at second or third
      trimester is less accurate and more difficult. It should be performed by a
      combination of sonographic signs (fetal sex, twin peak sign, location of the
      placenta(s), or counting the layers of the amniotic membrane) (ELNP2). When the
      diagnosis of chorionicity cannot be obtained, the patient should be offered a
      second scan in a reference center (expert opinion). CONCLUSIONS: The knowledge of
      the chorionicity is necessary for appropriate follow up of twin pregnancies.
      Ultrasound examination is a reliable method for the diagnosis of chorionicity
      early during the gestation.

PMID- 20141918
TI  - [Female stress urinary incontinence first line surgical treatment].
AB  - The sub uretral slings (SUS) have supplanted all other techniques in the
      treatment of stress urinary incontinence in first-line both at ease, results,
      consequences and cost. However the results are comparable with the abdominal
      retropubic colposuspension. The elective indication for BSU is stress
      incontinence. In the mixed incontinence, the results are satisfactory and depend
      on the degree of urge incontinence. The intrinsic sphincter deficiency with
      mobile uretra can be used in indications laying BSU. Only a BMI >= 35 is a
      pejorative factor on the outcome of the SUS. Currently, all routes retro pubic or
      obturator may be used without one being superior to another. For lack of
      comparative studies, using mini strips is currently under reserve. No
      recommendation can be given regarding the installation of urinary catheter in per
      and post operative. The relevance of cystoscopy for all routes used with the SUS
      is not formal. The SUS can be raised as an outpatient, but the patient must
      choose. It is the same type of anesthesia that is free and does not affect the
      results. The peri-urethral injections have no place as first choice because they
      offer a lower success rate. The SUS should be knitted polypropylene monofilament.
      Users should require the manufacturer that implants meet the AFNOR standard.

PMID- 20141919
TI  - [Complications of mid urethral sling procedures for surgical treatment of female
      stress urinary incontinence].
AB  - With the evolution of novel approaches to female urinary incontinence treatment,
      a new set of complications are being described. These complications are relative
      to the operative indication, the trajectory of needles, characteristics of used
      materials and the surgeon's experience. These complications, mostly minor,
      require an early diagnosis and an adequate management. Data on mini-slings are
      insufficient, so only complications of suburethral retropubic and transobturator
      tapes will be detailed. Our objective is to facilitate the identification of
      modifiable risk factors of surgery for female stress urinary incontinence
      complications and to propose recommendations for the use of suburethral sling
      procedures and prevention and management of their potential complications.

PMID- 20141920
TI  - [Urinary incontinence and pregnancy].
AB  - The goal of the current study was to systematically review the literature
      concerning urinary incontinence and pregnancy, in order to develop
      recommendations for clinical practice. The prevalence of urinary stress
      incontinence and overactive bladder symptoms increase with gestational age during
      pregnancy (from the first to the third trimester), and decrease during the third
      months following delivery. Obstetrics factors (position during delivery, length
      of the second part of the labour, forceps, episiotomy, epidural or pudendal
      anaesthesia) do not modify the risk of post-partum or long term urinary
      incontinence. At short term follow-up, caesarean delivery is associated with a
      lower rate of post-partum urinary incontinence. At long term follow-up, data are
      lacking. Non elective caesarean section is not associated with a decrease in the
      rate of post-partum or long-term urinary incontinence. Elective caesarean section
      and systematic episiotomy are not recommended methods for the prevention of post
      partum urinary incontinence (grade B), even in "high risk" women. Pelvic floor
      muscle therapy is the first line treatment for prenatal or post-partum urinary
      incontinence (grade A).

PMID- 20141921
TI  - [Urinary incontinence in aged women].
AB  - The assessment and treatment of urinary incontinence in aged women have age
      related specificities that we present from a literature review. Urinary
      incontinence is most often mixed: stress incontinence and urge incontinence. The
      coexistence of chronic retention is common and should be taken into account in
      treatment. Urinary incontinence de novo must find a trigger that will be
      corrected if possible. The treatment of urinary incontinence in aged women and
      young women are the same as long as no frailty is present. The definition of
      frailty is not consensual, but some criteria are regularly cited: age> 80 years,
      restricted mobility, functional decline, cognitive impairment. In frail aged
      women, geriatric assessment is necessary to adapt treatment, whether medical or
      surgical.

PMID- 20141922
TI  - [Urinary incontinence and genital prolapse].
AB  - Prolapse commonly coexists with lower urinary tract dysfunction. If symptomatic
      stress urinary incontinence is often described by patients with low stage pelvic
      organ prolapse, obstructive symptoms are common in patients with stage 3 or 4
      prolapse. Positive preoperative reduction testing in stress continent women
      planning prolapse repair is associated with a higher risk for postoperative
      leakage and clearly identify a high risk population. To date it has not been
      proven that urodynamic testing may provide more precise data than physical
      examination to advocate an additional stress urinary surgery at the time of
      prolapse repair. A systematic prophylactic Burch colposuspension significantly
      reduces the risk of postoperative SUI. In patients with occult SUI, a concomitant
      TVT at the time of vaginal prolapse surgery significantly reduces the risk of
      postoperative SUI. In patients without leakage during reduction testing, there is
      no evidence for performing a concurrent TVT.

PMID- 20141923
TI  - [Introduction. Every response is also a question].

PMID- 20141924
TI  - [Specificities of screening for aneuploidies in twin pregnancies].
AB  - OBJECTIVES: To determine the most efficient and tailored screening method for
      aneuploidies in twins for the French population. MATERIAL AND METHODS: Articles
      were searched using the PubMed and the Cochrane libraries. RESULTS: In cases of
      twin pregnancies, the aneuploidy's risk related to maternal age as well as
      gestational age must be considered as being the same as in singletons. In
      bichorionic twins, we have to consider individually the nuchal translucency
      thickness of each twin. In monochorionic twins, we have to consider a range of
      risks related to the nuchal translucency measurements of each twins. The
      additional benefit of maternal serum biochemistry screening in twins is not as
      established as in singletons. CONCLUSION: The most appropriate method of
      screening for aneuploidies in twin pregnancies is based during the first
      trimester of pregnancy on the risk related to maternal age combined with those
      related to the nuchal translucency measurement. In the absence of first-trimester
      screening, it is possible to offer a screening method based on the second
      trimester maternal serum biochemistry and/or by a targeted ultrasound.

PMID- 20141925
TI  - [Which invasive diagnostic procedure should we use for twin pregnancies:
      chorionic villous sampling or amniocentesis?].
AB  - OBJECTIVE: To describe invasive diagnostic procedures
      (amniocentesis/choriocentesis) and subsequent risks in twin pregnancies. MATERIAL
      AND METHODS: PubMed and Cochrane database investigations were conducted using
      following key words: twin gestation, amniocentesis, chorionic villous sampling,
      karyotype. Guidelines for twin management edicted by different societies were
      reviewed. RESULTS: Risk of pregnancy loss after invasive diagnostic procedure in
      twin pregnancies seems to be slightly higher to singletons, i.e about 1.5-2%
      after mid-trimester amniocentesis and about 2% after first trimester
      choriocentesis. Dual sampling is not always mandatory but can be performed on
      parent's request. Specific risks are associated with twins: redundant sampling,
      permutation or misidentification of affected twin in case of discordant status.
      Procedures should be performed by highly-skilled operators under permanent
      ultrasound-guidance. A scheme describing placental locations and funicular
      insertions appears to be useful for correct identification. If foeticide can be
      anticipated, diagnostic procedure and foeticide should be performed by the same
      operators. For amniocentesis, one or two needles can be used except for cases
      with infectious disease (two needles and two separate insertions required). For
      choriocentesis, sampling should be performed close to funicular insertions.
      CONCLUSION: First-trimester choriocentesis makes earlier diagnosis and earlier
      foeticide possible compared with mid-trimester amniocentesis. Both techniques
      require highly-skilled operators to reduce subsequent risks in the context of
      twin pregnancies.

PMID- 20141926
TI  - [Prenatal management of uncomplicated monochorionic biamniotic pregnancies].
AB  - Monochorionic pregnancies accounts for only 20% of twins but are responsible for
      most of their morbidity and mortality. There is no randomized study evaluating
      management of monochorionic pregnancies. Based on expert opinion, it is
      recommended that monochorionic pregnancies should be followed-up by practionners
      working with specialized centers with expertise in monochorionic pregnancies.
      Optimal follow-up should include a bi-monthly ultrasound evaluation.

PMID- 20141927
TI  - [Methods and organization].

PMID- 20141928
TI  - [Management of uncomplicated dichorionic twin pregnancy].
AB  - OBJECTIVES: To determine clinical recommendations for the management of
      uncomplicated dichorionic twin pregnancies. METHOD: Articles were searched using
      PubMed, Embase and Cochrane library. RESULTS: High level studies are rare.
      However, it is clear that dichorionic twin pregnancies are at risk for maternal
      or obstetrical complications as diabetes, preeclampsia and intra uterine growth
      restriction. Therefore, a specific follow up is recommended. CONCLUSIONS: A
      monthly clinical and ultrasound survey is recommended. The best time to deliver
      is between 38 and 40 weeks. Further studies are necessary to determine the best
      way to manage dichorionic twin pregnancies.

PMID- 20141929
TI  - [Twin pregnancies: where should we manage them? Where should they deliver?].
AB  - OBJECTIVES: To define where should twin pregnancies be managed and delivered.
      MATERIALS AND METHODS: A literature search was performed using the Pubmed and
      Cochrane database. Foreign societies guidelines were also consulted. RESULTS:
      There is little or no evidence to answer the question. Risk of premature labor
      and chorionicity are the two main factors involved in twin management. When there
      is a risk of prematurity, in utero transfer is recommended. Twin care must be
      performed by a team trained in the specificity of management according to
      chorionicity. There is not enough evidence to support specialized clinics. Labor
      and delivery need permanent and immediate disponibility of a perinatal team
      including an OB-gyn, an anesthesiologist and a pediatrician. CONCLUSION: Needs
      assessment and chorionicity are the best indicators to define the optimal place
      of care and delivery for twin pregnancies. More than a specific location, it
      seems more logical to define all necessary means to enforce an optimal management
      of these pregnancies.

PMID- 20141930
TI  - [Prevention of spontaneous preterm birth in asymptomatic twin pregnancies].
AB  - OBJECTIVES: To determine prenatal methods to predict and prevent spontaneous
      preterm birth in asymptomatic twin pregnancies. METHODS: Articles were searched
      using PubMed, Embase and Cochrane library. RESULTS: Uterine activity monitoring
      and bacterial vaginosis screening are not useful to predict preterm birth (EL2
      and EL3 respectively). Current literature data are contradictory and insufficient
      to determine whether fetal fibronectin and digital cervical assessment are
      predictors of preterm birth. History of preterm birth (EL4), and cervical length
      measurement by transvaginal ultrasonography (EL2) predict preterm birth.
      Nevertheless, there are no intervention studies that have evaluated cervical
      length measurement in the prevention of preterm birth. Hospital bedrest,
      prophylactic tocolytic and progesterone therapy, and prophylactic cervical
      cerclage in patients with or without short cervix have not been shown to be
      effective in preventing preterm birth. CONCLUSIONS: Prenatal methods to prevent
      spontaneous preterm birth in asymptomatic twin pregnancies are currently very
      limited.

PMID- 20141931
TI  - [Increase in twin maternities and consequences on health].
AB  - OBJECTIVES: To describe trends in twin maternity rates, factors which contribute
      to these trends, and risks associated with twin maternities for mothers and
      children. POPULATION AND METHOD: The review was done on population-based studies,
      preferably in France and the European Union. RESULTS: The rate of twin
      maternities was 15.6 p 1000 in 2008 and it increased by about 80% between 1972
      and 2006. This rise was explained mainly by advanced maternal age and the
      diffusion of fertility treatments. The major risks for twins were fetal and
      infant mortality, preterm delivery, small for gestational age, and cerebral
      palsy. The rate of preterm delivery (<37 weeks) was 44.3% in France in 2003, and
      the relative risk was 8.8 (95% CI: 7.8-10.0), when compared with single
      pregnancies. Maternal age and fertility treatments do not change very much the
      perinatal risk of twins. CONCLUSION: Twin pregnancies are a high risk group which
      needs more intensive medical care than single pregnancies. The perinatal
      information system should be improved in France to monitor perinatal indicators
      according to the number of fetuses in a proper way.

PMID- 20141932
TI  - [Management of twin twin transfusion syndrome].
AB  - The diagnosis of twin twin transfusion syndrome is an emergency and is generally
      easily done by ultrasound. Once the diagnosis is established patients should be
      referred rapidly for counselling and treatment within a network that can offer
      fetoscopic laser surgery as first-line treatment. Invasive treatments should be
      proscribed until then since they may impair fetoscopic visualization and
      therefore the overall prognosis, should this treatment be required. Depending on
      the presentation, other options may be offered such as cord coagulation,
      expectant management or delivery. Other treatment modalities such as
      amnioreduction or septostomy have almost no indications. Post-operative follow-up
      will be oriented by secondary hemodynamical complications and fetal neurological
      damage. An MRI may be a useful adjunct for ischemic/haemorrhagic brain injuries.
      Moderate prematurity may be justified, regarding the incidence of severe delayed
      complications.

PMID- 20141933
TI  - [Monoamniotic twins: diagnosis and management].
AB  - Monoamniotic twin pregnancies are necessarily monochorionic and are defined by
      the development of two fetuses in a single amniotic cavity. This pregnancy is the
      result of a division of the egg between the 8th and 13th day after fertilization.
      The diagnosis can and should be performed during the first trimester of
      pregnancy. Apart from the small risk of fetal transfusion syndrome, the
      specificities of these pregnancies are linked to greater risk of perinatal
      mortality, malformations, prematurity and the persistent risk of entanglement
      cords until birth. Intensified obstetrical monitoring eventually requiring
      hospitalization followed by a premature birth around 34 SA is recommended to
      improve perinatal outcomes with a reduction in prenatal mortality. Reorientation
      toward a neonatal Level III, the proposal of a systematic course of
      corticosteroids and elective delivery once lung maturation is achieved are
      recommended. There is not enough argument to recommend specific delivery mode,
      although cesarean section is performed by most authors to reduce the funicular
      risks.

PMID- 20141934
TI  - [Discordant anomaly in twin pregnancy].
AB  - The risk of fetal loss is multiplied by 4 in monochorionic pregnancies by
      comparison with dichorionic one. The incidence of selective growth retardation
      (sIUGR) is between 12.5 to 25%. This variation is explained by the mixture
      between pure twin-to-twin transfusion syndrome (TTTS) and pregnancies without
      TTTS but with a pure sIUGR. The ability to diagnose prenatally sIUGR is low; the
      positive predictive value is only 37% (EL4). The umbilical flow velocity
      waveforms with absent diastolic flow (Type II) or with diastolic intermittent
      flow (Type III) is clearly a strong risk factor of mortality of the IUGR and also
      a risk factor of leucomalacia of the bigger fetus (EL3). The observed incidence
      of malformations in twins is 4.05% versus 2.38% for singletons (OR=1.7 [IC 95%
      1.47-1.97]). Furthermore, the rate of fetal malformations is higher in
      monochorionic pregnancies by comparison with dichorionic one, 6.33% versus 3.43%
      (OR=1.8 [IC 95% 1.3-2.5]) (EL3). In the majority of the cases, the malformation
      is concerning only one fetus. The most frequent malformations are those of the
      central nervous system by comparison with singletons, those of the urinary tract
      and the cardiovascular malformations. Monozygotic pregnancies are not necessarily
      phenotypically and genetically identical. In situation of asymmetrical
      malformation, it is necessary to propose fetal karyotype of the malformed fetus.
      In case aneuploidy of the malformed fetus, secondarily it will be necessary to
      explore the other apparently normal one. Uniparental disomy should be suspected
      in such situation (EL3). In TRAP sequence, an intensive follow up should be
      organised with serial measurement of the respective size of the acardiac fetus
      and the normal one, Doppler exploration should be done to look for early sign of
      cardiac decompensation (expert viewpoint). In dichorionic pregnancies, when the
      malformation is threatening the whole pregnancy like anencephaly, a selective
      feticide allow a prolongation of the pregnancy, but with a risk of fetal loss of
      8% and a risk of iatrogenic prematurity of 12%. In such situation, it could be
      wise to evaluate the evolution or to wait until the third trimester to undergo
      the procedure (EL3). In monochorionic pregnancies, in the same situation of
      anencephalic fetus the best option is bipolar cord coagulation. The result seems
      to be better after 18 weeks of gestation (EL4). There is a 20% risk of premature
      rupture of membrane. In the up to date analysis of the literature, there is no
      formal indication of selective feticide expect case of TRAP sequence with cardiac
      decompensation of the normal fetus. The very special situation of sIUGR is the
      object of a randomized trial. In all cases the active participation of the
      patients to the therapeutic option is mandatory (expert viewpoint).

PMID- 20141935
TI  - A review on ochratoxin A occurrence and effects of processing of cereal and
      cereal derived food products.
AB  - Ochratoxin A (OTA) continues to grab global attention and concern for the hazard
      and impact that embody for both human and animals, based on its toxicity and
      occurrence. Despite OTA has been described in a myriad of foodstuffs, cereal and
      its derivatives remain the major contributors to OTA exposure. For that reason, a
      critical review on OTA occurrence reported by recent studies worldwide focusing
      on unprocessed and processed cereal foodstuffs is made in this work. Special
      attention is drawn to the major cereal derived products, namely flour, bread,
      breakfast cereals, baby/infant foods and the inherently involved technological
      food processing methods and its influence on the redistribution and chemical
      modification of OTA. The paper further examines the factors that influence the
      OTA content of cereal and its derived products, explicitly the different
      ecological niches of the ochratoxigenic mycobiota -Aspergillus spp. and
      Penicillium verrucosum, the agricultural practice involved, harvest procedures
      and storage conditions, the type of grain, and the nature and extent of
      technological processing as well as the ultimate stages of analytical quality
      level of the sampling and analysis of the suspected ingredients or foods.

PMID- 20141936
TI  - Cross-contamination of fresh-cut lettuce after a short-term exposure during pre
      washing cannot be controlled after subsequent washing with chlorine dioxide or
      sodium hypochlorite.
AB  - Chlorine dioxide (ClO(2)) has been postulated as an alternative to sodium
      hypochlorite (NaClO) for fresh-cut produce sanitization to avoid risks associated
      with chlorination by-products. Experiments were performed to determine the
      prevention of cross-contamination of fresh-cut lettuce by Escherichia coli using
      chlorine dioxide (3 mg/L) or sodium hypochlorite (100 mg/L) as sanitation agents.
      The efficacy of these sanitation solutions was evaluated simulating as much as
      possible the conditions of a fresh-cut processing line. Thus, to evaluate the
      potential risk of cross-contamination during pre-washing, inoculated fresh-cut
      lettuce was pre-washed and after that non-inoculated lettuce was then pre-washed
      in the same water. After this pre-washing, non-inoculated lettuce was cross
      contaminated, changing from 0 to 3.4 log units of E. coli cells. During washing
      with sanitizers, none of the tested sanitation agents significantly reduced E.
      coli counts in both inoculated and cross-contaminated lettuce. These results
      suggest that when cross-contamination occurs, even if the event is recent,
      subsequent sanitation steps are inefficient for inactivating E. coli cells on the
      vegetable tissue. However, chlorine dioxide and sodium hypochlorite solutions
      were able to inactivate most E. coli cells that passed from inoculated product to
      wash water. Therefore, they might be able to avoid cross-contamination between
      clean and contaminated product during the washing step. Scanning electron
      microscopy micrographs indicated that bacterial cells were mainly located in
      clusters or tissue stomata where they might be protected, which explains the low
      efficacy of sodium hypochlorite and chlorine dioxide solutions observed in this
      study.

PMID- 20141937
TI  - Wine yeast molecular typing using a simplified method for simultaneously
      extracting mtDNA, nuclear DNA and virus dsRNA.
AB  - Quick and accurate methods are required for the identification of industrial,
      environmental, and clinical yeast strains. We propose a rapid method for the
      simultaneous extraction of yeast mtDNA, nuclear DNA, and virus dsRNA. It is
      simpler, cheaper, and faster than the previously reported methods. It allows one
      to choose among a broad range of molecular analysis approaches for yeast typing,
      avoiding the need to use of several different methods for the separate extraction
      of each nucleic acid type. The application of this method followed by the
      combined analysis of mtDNA and dsRNA (ScV-M and W) is a highly attractive option
      for fast and efficient wine yeast typing.

PMID- 20141938
TI  - Alternative disinfection techniques to extend the shelf life of minimally
      processed iceberg lettuce.
AB  - Chlorination continues to be widely used by the fresh-cut industry for washing
      and disinfecting minimally processed fruits and vegetables. However, as
      chlorination has been reported to produce unhealthy by-products such as,
      chloramines and trihalomethanes, many alternative methods have been reported in
      the literature. This study examined the use of silver and hydrogen peroxide as
      possible alternative to chlorination. The results revealed an obvious
      bactericidal effect of hydrogen peroxide, silver and their combination on
      spoilage organisms. Combination of electrochemically generated silver (5 ppm) and
      hydrogen peroxide (0.4 ppm) caused significant (P < 0.05) reduction in the total
      plate count (0.87 log), Pseudomonas (2.66 logs), Enterobactericeae (1.61 logs)
      and yeast and mould (1.60 logs) immediately after washing in comparison to water
      washed shredded lettuce. However, washing with chlorinated water (5 ppm) under
      same conditions revealed insignificant reduction in TPC (0.17 log), Pseudomonas
      (0.60 log), Enterobactericeae (0.15 log) or yeast and mould (0.81 log) counts.
      Results revealed also that both sources of silver (electrochemical silver and
      silver nitrate) have similar disinfecting effects, however, electrochemical
      silver maintained the quality of washed lettuce.

PMID- 20141939
TI  - On the selection of relevant environmental factors to predict microbial dynamics
      in solidified media.
AB  - Several studies have shown that food structure causes slower growth rates and
      narrower growth boundaries of bacteria compared to laboratory media. In
      predictive microbiology, both a(w) or corresponding solute concentration (mainly
      NaCl) have been used as a growth influencing factor for kinetic models or
      growth/no growth interface models. The majority of these models have been based
      on data generated in liquid broth media with NaCl as the predominant a(w)
      influencing solute. However, in complex food systems, other a(w) influencing
      components might be present, next to NaCl. In this study, the growth rate of
      Salmonella typhimurium was studied in the growth region and the growth/no growth
      response was tested in Tryptic Soy Broth at 20 degrees C at varying gelatin
      concentration (0, 10, 50 g L(-1) gelatin), pH (3.25-5.5) and water activity
      (a(w)) (0.929-0.996). From the viewpoint of water activity, the results suggest
      that NaCl is the main a(w) affecting compound. However, gelatin seemed to have an
      effect on medium a(w) too. Moreover, there is also an interaction effect between
      NaCl and gelatin. From the microbial viewpoint, the results confirmed that the
      a(w) decreasing effect of gelatin is less harmful to cells than the effect of
      Na(+) ions. The unexpected shift of the growth/no growth interface to more severe
      conditions when going from a liquid medium to a medium with 10 g L(-1) gelatin is
      more pronounced when formulating the models in terms of a(w) than in terms of
      NaCl concentrations. At 50 g L(-1) gelatin, the model factored with NaCl
      concentration shifts to milder conditions (concordant to literature results)
      while the model with a(w) indicates a further shift to more severe conditions,
      which is due to the water activity lowering effect of gelatin and the interaction
      between gelatin and NaCl. The results suggest that solute concentration should be
      used instead of a(w), both for kinetic models in the growth region and for
      growth/no growth interface models, if the transferability of models to solid
      foods is to be increased.

PMID- 20141940
TI  - Study of the lactic acid bacteria throughout the manufacture of dry-cured lacon
      (a Spanish traditional meat product). Effect of some additives.
AB  - Total aerobic mesophilic microflora (on SPC agar), lactic acid bacteria (on MRS
      agar) and lactobacilli (on Rogosa agar) were enumerated in samples from the
      surface and the interior of the pieces throughout the manufacture of six batches
      of lacon. Three of the batches were made without additives and three with
      additives (glucose (2 g/kg), sodium nitrite (E(250)) (125 mg/kg), sodium nitrate
      (E(251)) (175 mg/kg), sodium ascorbate (E(301)) (500 mg/kg), and sodium citrate
      (E(331)) (100 mg/kg)). The counts decreased throughout the manufacturing process,
      particularly after the salting stage. The use of additives did not affect the
      counts or the evolution of the microbial groups, except for the lactobacilli,
      which were present in higher numbers in the batches with additives. In four
      batches (two without and two with additives), from MRS agar and from Rogosa agar
      plates, 10 colonies were randomly taken from each sampling point of each batch
      (five from the surface sample and five from the interior sample) and from each
      culture medium; a total of 224 strains from MRS agar, and 176 strains from Rogosa
      agar that were identified by classical methods. The MRS agar displayed moderate
      selectivity for the isolation of lactic acid bacteria, and only 59% of the
      isolated strains belonged to this microbial group. Homofermentative and
      facultative heterofermentative lactobacilli (particularly Lactobacillus curvatus
      and Lactobacillus sakei) were the most abundant species isolated on this medium.
      The selectivity of the Rogosa agar for lactobacilli was extremely high. The
      species of lactobacilli isolated on this medium at different stages of
      manufacture of the four batches of lacon were consistent with those isolated from
      MRS agar. The use of additives in the lacon did not appreciably affect the kinds
      and proportions of species isolated on either MRS agar or Rogosa agar.

PMID- 20141941
TI  - Development of a real-time RT-PCR method for enumeration of viable
      Bifidobacterium longum cells in different morphologies.
AB  - Viability of probiotic bacteria is traditionally assessed by plate counting which
      has several limitations, including underestimation of cells in aggregates or
      chains morphology. We describe a quantitative PCR (qPCR)-based method for an
      accurate enumeration of viable cells of Bifidobacterium longum NCC2705 exhibiting
      different morphologies by measuring the mRNA levels of cysB and purB, two
      constitutively expressed housekeeping genes. Three primer-sets targeting short
      fragments of 57-bp of cysS and purB and one 400-bp fragment of purB were used.
      Cell quantification of serially diluted samples showed a good correlation
      coefficient of R(2) 0.984 +/- 0.003 between plate counts and qRT-PCR for all
      tested primer sets. Loss of viable cells exposed to a lethal heat stress (56
      degrees C, 10, 20 and 30 min) was estimated by qRT-PCR and plate counts. No
      significant difference was observed using qRT-PCR targeting the 400-bp fragment
      of purB compared to plate counts indicating that this fragment is a suitable
      marker of cell viability. In contrast, the use of the 57-bp fragments led to a
      significant overestimation of viable cell counts (18 +/- 3 and 7 +/- 2 fold for
      cysB and purB, respectively). Decay of the mRNA fragments was studied by
      treatment of growing cells with rifampicin prior qRT-PCR. The 400-bp fragment of
      purB was faster degraded than the 57-bp fragments of cysB and purB. The 400-bp
      fragment of purB was further used to enumerate viable cells in aggregate state.
      Cell counts were more than 2 log(10) higher using the qRT-PCR method compared to
      plate counts. Growing interest in probiotic characteristics of aggregating
      bacteria cells make this technique a valuable tool to accurately quantify viable
      probiotic bacteria exhibiting heterogeneous morphology.

PMID- 20141942
TI  - The microbiological safety of ready-to-eat specialty meats from markets and
      specialty food shops: a UK wide study with a focus on Salmonella and Listeria
      monocytogenes.
AB  - From 2359 specialty meats (continental sausages, cured/fermented, dried meats)
      sampled from markets and specialty food shops, 98.9% of samples were of
      satisfactory or acceptable microbiological quality. However, 16 (0.7%) were
      unsatisfactory as a result of Escherichia coli, Staphylococcus aureus or Listeria
      spp. contamination (>or=10(2) CFU/g), and nine (0.4%) were unacceptable due to
      presence of Salmonella spp. or Listeria monocytogenes (>10(2) CFU/g). Meats with
      unacceptable levels of L. monocytogenes were within shelf life (range: 8-143 days
      remaining). Nine different subtypes of L. monocytogenes were detected with
      sero/AFLP type 1/2c VII predominating (37%), although this subtype was not
      overrepresented in any particular meat type (P > 0.05). Ninety-six percent of
      continental sausages and cured/fermented products were stored at <8 degrees C at
      premises, including seven of the nine unacceptable samples. These nine meats were
      all pre-packed prior to supply to retail premises (OR = 0.1 P = 0.003) indicating
      that contamination with bacterial pathogens occurred earlier in the production
      chain. Most samples (72.7%, 8/11) with unsatisfactory levels of E. coli were
      sliced on request, suggesting cross-contamination at point of sale. This study
      highlights the importance of ensuring that products do not become contaminated
      before final packaging, that storage conditions are controlled, and that
      durability dates are an accurate indication of the shelf life of the product so
      as to minimise the potential for L. monocytogenes to be present at levels
      hazardous to health at the point of sale.

PMID- 20141943
TI  - The effects of temperature, chlorine and acids on the survival of Listeria and
      Salmonella strains associated with uncooked shrimp carapace and cooked shrimp
      flesh.
AB  - The purpose of this study was to assess the influence of the association of
      Listeria and Salmonella with shrimp surfaces on the effects of temperature,
      chlorine and acids on their survival. Planktonic, attached and colonized cells of
      Listeria monocytogenes Scott A, L. monocytogenes V7, Salmonella Senftenberg 1734b
      and S. Typhimurium ATCC 14028 were challenged with high (50 degrees , 60 degrees
      and 70 degrees C) and low (4 degrees C) temperature, 100 ppm sodium hypochlorite
      solution, and acetic, hydrochloric and lactic acids (pH 4.0). Attached and
      colonized Listeria and Salmonella showed significantly greater (p < 0.05)
      resistance to heat ( approximately 1.3-2.6 fold increase in D-values),
      hypochlorite ( approximately 6.6 >or= 40.0 fold) and acids ( approximately 4.0
      9.0 fold) than their planktonic counterparts. There were no significant
      differences (p > 0.05) in the survival of planktonic, attached or colonized cells
      of Listeria and Salmonella stored under refrigerated conditions. The association
      of Listeria and Salmonella with shrimp surfaces enhances their resistance to
      heat, chlorine and acids. Both attachment to, and subsequent colonization of,
      shrimp surfaces by pathogens may reduce the efficacy of methods used in their
      control. Strategies to reduce attachment of these pathogens to shrimp are
      required to assure safety of this product.

PMID- 20141944
TI  - Identification and quantification of acetic acid bacteria in wine and vinegar by
      TaqMan-MGB probes.
AB  - A Real-Time PCR (RT-PCR) assay was developed using TaqMan minor groove binder
      (MGB) probes for the specific detection and quantification of five acetic acid
      bacteria (AAB) species (Acetobacter pasteurianus, Acetobacter aceti,
      Gluconacetobacter hansenii, Gluconacetobacter europaeus and Gluconobacter
      oxydans) in wine and vinegar. The primers and probes, designed from the 16S rRNA
      gene, showed good specificity with the target AAB species. The technique was
      tested on AAB grown in glucose medium (GY) and inoculated samples of red wine and
      wine vinegar. Standard curves were constructed with the five target species in
      all these matrices. Quantification was linear over at least 5 log units using
      both serial dilution of purified DNA and cells. When this technique was tested in
      GY medium and inoculated matrices, at least 10(2)-10(3) cells/ml were detected.
      To quantify low populations of AAB in microbiologically complex samples, a PCR
      enrichment including part of the 16S-23S rRNA gene ITS region was needed to
      increase the amount of target DNA compared to non-target DNA. The RT-PCR assay
      used in this study is a reliable, specific and fast method for quantifying these
      five AAB species in wine and vinegar.

PMID- 20141945
TI  - Effect of high pressure on the microbiological quality of cooked chicken during
      storage at normal and abuse refrigeration temperatures.
AB  - Vacuum-packaged cooked poultry meat was treated at a range of pressures (400-600
      MPa) and hold times (1, 2 and 10 min), followed by storage at 4 degrees , 8
      degrees or 12 degrees C for up to 35 days. Weissella viridescens was found to be
      the dominant microorganism in the pressure-treated meat, constituting 100% of the
      microflora identified at 500 and 600 MPa. None of the pressure-treated samples
      had obvious signs of spoilage during the 35 day storage period, even when the
      Weissella count was >7 log(10) cfu/g. Studies on a typical W. viridescens isolate
      showed it to be relatively pressure-resistant in poultry meat, with <1 log
      reduction in numbers after a treatment of 2 min at 600 MPa. Agar diffusion assays
      showed that the isolate also caused the inhibition of a number of Gram-positive
      and Gram-negative pathogens, including strains of Clostridium botulinum, Listeria
      monocytogenes, Bacillus cereus and Escherichia coli. The selection of a pressure
      resistant organism, such as this Weissella sp. could be advantageous in extending
      the shelf-life, and also microbiological safety, of the cooked meat, as it could
      give protection in addition to the pressure treatment itself.

PMID- 20141946
TI  - Antibacterial activity of carvacrol and 2-nitro-1-propanol against single and
      mixed populations of foodborne pathogenic bacteria in corn flour dough.
AB  - Cereal doughs are an important part of human diet, but at the same time can act
      as vehicles for the transmission of human pathogenic bacteria. In the present
      study, four pathogenic or toxinogenic bacteria (Escherichia coli O157:H7,
      Salmonella enterica serovar Enteritidis, Bacillus cereus and Staphylococcus
      aureus) were inoculated in a dough made from corn flour in combination with the
      single antimicrobial compounds carvacrol and 2-Nitro-1-propanol (2NPOH). Survival
      of single and mixed populations in the treated doughs incubated at 37 degrees C
      was followed by culture-dependent and independent methods (TTGE). All strains
      were completely inactivated within 24 h by the tested compounds at 5% final
      concentration, but showed variable inhibition at lower concentrations of 0.5% and
      2%. Sensitivity to antimicrobial compounds was in general modified when strains
      were tested in cocultures compared with single cultures. B. cereus was more
      sensitive to carvacrol (minimum bactericidal concentration, MBC, 0.5%) in
      coculture with S. aureus. It was also more sensitive to 2NPOH in cocultures with
      S. aureus and with S. enterica (MBC, 2% in both cases). S. aureus was more
      resistant to carvacrol (MBC, 5%) in cocultures with B. cereus, E. coli, as well
      as S. enterica. However, sensitivity to 2NPOH was not modified in any of the
      coculture experiments (MBC, 2%). E. coli was more resistant to carvacrol (MBC,
      5%) in cocultures with S. aureus and with S. enterica. Resistance of E. coli to
      2NPOH also increased in cocultures with B. cereus (MBC, 5%) and with S. aureus
      (MBC, 2%), but not with S. enterica (MBC, 0.5%). S. enterica was more resistant
      to carvacrol (MBC, 5%) in cocultures with E. coli, but it was more sensitive to
      2NPOH in cocultures with B. cereus as well as with S. aureus (MBC, 2% in both
      cases). TTGE analysis of survivors from cocultures treated with 2NPOH or
      carvacrol allowed a good estimation of the identity of survivors according to
      their DNA band patterns. Results from this study indicate that the efficacy of
      antimicrobials such as carvacrol and 2NPOH is greatly influenced by the
      complexity of the microbial populations under target and the relationships
      between individual populations.

PMID- 20141947
TI  - Heat shock effects on the viability of Cronobacter sakazakii during the
      dehydration, fermentation, and storage of lactic cultured milk products.
AB  - In the present study, the viability of heat-shocked and non-shocked Cronobacter
      sakazakii, a foodborne pathogen, after drying and during the fermentation as well
      as storage of lactic cultured milk was evaluated. It was found that heat shock
      increased the viability of C. sakazakii. The pure culture of C. sakazakii,
      regardless of heat shock, grew rapidly in skim milk with a viable population of
      ca. 8.59-8.70 log cfu/ml after ca. 48 h of cultivation. Thereafter, the viable
      population of C. sakazakii remained stable. While in the mix culture with
      Streptococcus thermophilus or Lactobacillus bulgaricus, a marked reduction in the
      viable population of C. sakazakii was noted after 24 h of cultivation in skim
      milk. Nevertheless, at the end of fermentation, the heat-shocked C. sakazakii had
      a viable population of 5.93-6.01 log cfu/ml, which is significantly higher (P <
      0.05) than that of non-shocked cells of 4.96-4.99 log cfu/ml. While the presence
      of C. sakazakii did not affect the growth of lactic acid bacteria in skim milk.
      Additionally, heat shock was found to enhance the survival of C. sakazakii after
      freeze-drying or spray-drying and during the storage of the lactic fermented milk
      products (pH 4.3) at 5 degrees C for 48 h.

PMID- 20141948
TI  - Diversity of culturable microorganisms and occurrence of Listeria monocytogenes
      and Salmonella spp. in Tuber aestivum and Tuber melanosporum ascocarps.
AB  - The aim of this study was to investigate the total mesophilic microorganisms,
      Pseudomonas genus, Enterobacteriaceae family, mold and yeast counts and the
      presence of Listeria monocytogenes and Salmonella spp on Tuber aestivum and Tuber
      melanosporum ascocarps. The results confirmed that the major percentage of the
      microorganisms, approximately 9.0 log ufc/g, were present in the peridium, the
      glebas of healthy truffles being practically free of microorganisms. The
      predominant microbial group was the Pseudomonas averaging 8.3 and 8.4 log cfu/g
      on T. aestivum and T. melanosporum whole ascocarps, respectively. The
      Enterobacteriaceae also achieved high populations, especially in T. aestivum
      truffles, with 6.3 log cfu/g. Molds and yeasts never exceeded 5.0 log cfu/g. The
      characterization of the isolates revealed that the fluorescens pseudomonads were
      the most prevalent. Raoultella terrigena and Enterobacter intermedius were the
      dominant Enterobacteriaceae. The identification of the yeast isolates revealed
      five species: Debaryomyces hansenii, Issatchenkia scutulata, Rhodotorula
      aurantiaca, Saccharomyces dairensis and Trichosporon beigelii subspecies A and B.
      The mold genera detected in both species of truffles were Aspergillus,
      Cladosporium, Penicillium and Fusarium, Trichoderma being present only in T.
      aestivum. L. monocytogenes was found in 10% of the samples of T. aestivum
      analysed but Salmonella spp. was not detected. Knowledge of the microbial
      population in terms of possible food borne and pathogen microorganisms is very
      useful for establishing successful disinfection and storage methods to prolong
      the shelf-life of ascocarps of T. aestivum and T. melanosporum.

PMID- 20141949
TI  - Biodiversity of indigenous staphylococci of naturally fermented dry sausages and
      manufacturing environments of small-scale processing units.
AB  - The staphylococcal community of the environments of nine French small-scale
      processing units and their naturally fermented meat products was identified by
      analyzing 676 isolates. Fifteen species were accurately identified using
      validated molecular methods. The three prevalent species were Staphylococcus
      equorum (58.4%), Staphylococcus saprophyticus (15.7%) and Staphylococcus xylosus
      (9.3%). S. equorum was isolated in all the processing units in similar proportion
      in meat and environmental samples. S. saprophyticus was also isolated in all the
      processing units with a higher percentage in environmental samples. S. xylosus
      was present sporadically in the processing units and its prevalence was higher in
      meat samples. The genetic diversity of the strains within the three species
      isolated from one processing unit was studied by PFGE and revealed a high
      diversity for S. equorum and S. saprophyticus both in the environment and the
      meat isolates. The genetic diversity remained high through the manufacturing
      steps. A small percentage of the strains of the two species share the two
      ecological niches. These results highlight that some strains, probably introduced
      by the meat, will persist in the manufacturing environment, while other strains
      are more adapted to the meat products.

PMID- 20141950
TI  - Assessment of the anti-listerial activity of microfloras from the surface of
      smear-ripened cheeses.
AB  - The anti-listerial activity of microfloras from the surface of various smear
      ripened cheeses was evaluated using four methods that were then compared. Method
      A measured the anti-listerial potential of supernatants from short-time liquid
      cultures, whereas in Method B, a model cheese was co-inoculated with the
      microflora and Listeria innocua test strains. Method C was based on successive
      propagations of the microfloras on this model cheese, and Method D on successive
      propagations of the microfloras together with Listeria test strains. Anti
      listerial activity considerably depended on the microflora used. Significant
      correlations were obtained between Methods A and B and Methods C and D. With
      Methods C and D, the highest anti-listerial activity was obtained with the
      microflora from a Livarot-type cheese (FC12). To investigate the cause of the
      anti-listerial activity of FC12, Fourier Transform InfraRed (FTIR) analyses of
      microbial populations were performed on the original microflora as well as on the
      microflora after propagations on the model cheese. The composition of FC12 had
      changed considerably upon propagation, and in the propagated microflora, the
      population of yeasts was dominated by Yarrowia lipolytica strains, whereas the
      population of bacteria was dominated by Vagococcus species.

PMID- 20141951
TI  - The temporal, PFGE and resistance pattern associations suggest that poultry
      products are only a minor source of human infections in western Finland.
AB  - In order to compare human and retail poultry meat thermophilic Campylobacter
      isolates originating in a regional area in Western Finland, minimum inhibitory
      concentration (MICs) for six antimicrobials (96 isolates) and pulsed-field gel
      electrophoresis (PFGE) (102 isolates) were analysed. Campylobacter spp. were
      detected in 10.5% out of 305 fresh poultry products studied; 29 (90.5%) isolates
      were identified as Campylobacter jejuni. Among the 70 human isolates, 66 (94.3%)
      isolates were identified as C. jejuni. Only one C. jejuni domestic poultry
      isolate showed resistance (ampicillin), whereas domestic human C. jejuni isolates
      were more commonly resistant to ciprofloxacin, nalidixic acid, ampicillin and
      tetracycline. The resistance in foreign human isolates was significantly more
      common than among domestic isolates. PFGE analysis with KpnI restriction enzyme
      resulted in 59 different PFGE types among the poultry and human isolates. Three
      types were detected first in poultry meat and thereafter during the following
      month in domestic human samples, whereas the other conjoint types were detected
      only after many months. This study suggests that poultry products play only a
      minor role in human campylobacteriosis in the study area and that the resistance
      found in domestic human isolates is not likely related to retail poultry meat
      products.

PMID- 20141952
TI  - D. Emerick Szilagyi, MD, 1910-2009; editor, 1984-1990.

PMID- 20141953
TI  - Invited commentary.

PMID- 20141954
TI  - Endovascular repair of ruptured thoracic aortic aneurysms is associated with high
      perioperative mortality and morbidity.
AB  - PURPOSE: To analyze early and midterm results after endovascular treatment of
      ruptured thoracic aortic aneurysms (rTAA). METHODS: Between January 1997 and
      January 2009, a total of 236 patients received thoracic aortic repair in our
      institution; 23 patients (14 men; median age, 75 years; range, 60-88 years) due
      to a ruptured thoracic aortic aneurysm (rTAA). Rupture was defined according to
      computed tomography angiography (CTA) criteria with definite sign for hemorrhage
      outside the aortic wall. Patients with symptomatic TAA but with normal CT scans
      were excluded. A retrospective analysis of these patients was performed. Median
      follow up was 28 months (range, 0.1-82.5 months) and included serial aortic
      imaging at discharge, six, and 12 months and annually thereafter. RESULTS:
      Technical success rate was 87%. The overall in hospital mortality was 48% with
      predominantly (50%) cardiac complications. Neurological complications occurred in
      three patients, two patients suffered from a transient ischemic attack
      (TIA)/stroke, and one patient experienced paraplegia after early conversion to
      open surgery. Primary endoleaks were seen in four of 25 patients (16%); no
      secondary endoleak was observed. Early conversion was necessary in two patients
      caused by an aortoesophageal fistula. The one- and three-year survival rates were
      37.3% and 29.9% with no aortic or procedure-related death during follow up.
      Reintervention was necessary in four of 25 patients (16%). Cox regression
      analysis revealed preoperative renal insufficiency (hazard ratio [HR] 5.85, P =
      .0073) as an independent predictor of perioperative death. CONCLUSIONS: The
      endovascular treatment of ruptured thoracic aortic aneurysms is associated with a
      high perioperative mortality and morbidity as well as poor midterm survival.
      Renal insufficiency proved to be an independent risk factor for perioperative
      death.

PMID- 20141955
TI  - Invited commentary.

PMID- 20141956
TI  - Open surgical reconstruction of the internal carotid artery aneurysm at the base
      of the skull.
AB  - OBJECTIVES: Aneurysms of the internal carotid artery (ICA) at the base of the
      skull are uncommon dangerous lesions whose management remains unclear. The aim of
      this retrospective study is to report a standardized surgical technique of ICA
      reconstruction with long-term results. METHODS: Between 1988 and 2005, 13
      patients (11 men; age 18 to 76 years, mean 42.6 years) underwent lateral skull
      base approach with cervical-to-petrous carotid artery bypass for repair of ICA
      aneurysms. Principal elements of the technique were: partial resection of the
      parotid gland without rerouting of the facial nerve; luxation of mandibula;
      drilling of the bone. RESULTS: The 13 patients had unilateral aneurysm of the ICA
      at the base of the skull. Four aneurysms were of atherosclerotic origin; six
      fibromuscular dysplasia; two post-traumatic; one cause was undetermined. The mean
      diameter of the aneurysms was 12 mm (range, 7-21 mm). Twelve patients were
      symptomatic: six presented neurological events (four strokes, two transient
      ischemic attack [TIA]); two retinal events; three compressive symptoms (two
      Horner's syndrome and one paralysis of the glossopharyngeal nerve); one patient
      presented a visible pulsatile mass in the neck. One patient was asymptomatic.
      There were no post-operative deaths, one TIA, 13 transient palsies of the lower
      facial nerve, and one transient palsy of accessory nerve. Palsy of cranial nerves
      was partial and disappeared within a mean of 5.6 months (range, 1-10 months). The
      postoperative angiogram showed patency in all but one case (one asymptomatic
      thrombosis). During follow-up (mean, 152 months), there was one unrelated death,
      one focal epileptic seizure, and one controlateral TIA. In November 2008, duplex
      showed patency of all 11 grafts (one death, one thrombosis). At 10 years, the
      survival, cumulative stroke-free survival, ipsilateral stroke-free, and patency
      rates was were 90.9%, 100%, 100%, and 92.3%. CONCLUSION: Venous graft bypass from
      the cervical-to-petrous ICA can be performed safely with such an approach and
      produces durable satisfactory results.

PMID- 20141957
TI  - Echolucent or predominantly echolucent femoral plaques predict early restenosis
      after eversion carotid endarterectomy.
AB  - OBJECTIVE: Although the association between vulnerable lesions and cardiovascular
      events is well established, little is known about their relationship to
      postsurgery restenosis. To address this issue, we initiated a prospective,
      nonrandomized study to examine the femoral plaques on both sides in patients who
      were undergoing eversion carotid endarterectomy (CEA) and were longitudinally
      followed-up for early restenosis development. METHODS: The final analysis
      enrolled 321 patients (189 women) with a median age of 67.0 years (interquartile
      range, 59.0-73.0 years), who underwent eversion CEA (2005 to 2007). Using duplex
      ultrasound scanning, we evaluated 321 common femoral atherosclerotic lesions on
      the day before CEA. A quantitative scale was used to grade the size of plaques as
      grade 1, one or more small plaques (<20 mm2); grade 2, moderate to large plaques;
      and grade 3, plaques giving flow disturbances. The plaque morphology in terms of
      echogenicity was graded as echolucent, 1; predominantly echolucent, 2;
      predominantly echogenic, 3; echogenic 4; or calcified, 5. The plaque surface was
      categorized as smooth, irregular, or ulcerated. The patients underwent carotid
      duplex ultrasound imaging at 6 weeks and at 6, 12, and 24 months after CEA. Mann
      Whitney U test, chi2 test, and multivariate logistic regression were used for
      statistical evaluation. RESULTS: Internal carotid artery restenosis of > or = 50%
      was detected in 33 patients (10.28%) in the operated region. Neither the size
      (grade 1, P = .793; grade 2, P = .540; grade 3, P = .395) nor the surface
      characteristics of the femoral plaques (smooth, P = .278; irregular, P = .281;
      ulcerated, P = .934) were significantly different between the patients with and
      without carotid restenosis. Echolucent-predominantly echolucent femoral lesions
      were an independent predictor of recurrent carotid stenosis (adjusted odds ratio,
      5.63; 95% confidence interval, 2.14-10.89; P < .001). CONCLUSION: Ultrasound
      evaluation of femoral plaque morphology before CEA can be useful for identifying
      patients at higher risk for carotid restenosis.

PMID- 20141958
TI  - Preoperative functional status predicts perioperative outcomes after
      infrainguinal bypass surgery.
AB  - OBJECTIVE: Infrainguinal surgical bypass (BPG) is a durable method for lower
      extremity revascularization, but is accompanied by significant 30-day morbidity
      and mortality (MM). The goal of this study is to relate preoperative functional
      status, a defined metric in the National Surgical Quality Improvement Program
      (NSQIP) database, to perioperative MM. METHODS: Between January 1, 2005 and
      December 31, 2007, all patients who underwent BPG from the NSQIP private sector
      database were reviewed. The primary end-point was 30-day MM. Patients were
      stratified by preoperative functional status: independent (IND) vs dependent
      (DEP). Associated patient demographic/clinical data were analyzed using
      univariate and multivariate methods. Composite odds ratios were constructed with
      clusters of high-risk comorbidities. RESULTS: There were 5639 BPG patients (4600
      [81.6%] IND and 1039 [18.4%]) DEP. DEP patients were significantly older (71.6 +/
      11.8 vs 66.8 +/- 11.8 years; P < .0001), had more chronic obstructive pulmonary
      disease (COPD) (16.7% vs 11.4%; P < .0001), diabetes (54.2% vs 40.7%; P < .0001),
      dialysis dependence (16.4% vs 5.6%; P < .0001), and critical limb ischemia (64.6%
      vs 44.0%; P < .0001). DEP patients had a higher incidence of death (6.1% vs 1.5%;
      P < .0001) and major complications (30.3% vs 14.2%; P < .0001). DEP was an
      independent predictor of major complications (odds ratio [OR]: 2.0; 95%
      confidence interval [CI]: [1.7-2.4]; P < .0001) major systemic complications (2.5
      [1.9-3.2]; P < .0001), major operative site complications (1.6 [1.4-1.9]; P <
      .0001) and death (2.3[1.6-3.4]; P < .0001). The combination of DEP with emergency
      surgery, Cr > 1.8, or rest pain increased the odds of major complications by
      five, seven, or 11-fold, respectively. The combination of DEP with hemodialysis,
      emergency surgery, or age > or = 80 years increased the odds of death by 13, 38,
      or 87-fold, respectively. CONCLUSION: Preoperative DEP is significantly
      correlated with all adverse 30-day outcomes in BPG patients. Furthermore, when
      combined in high-risk composites with specific preoperative clinical variables,
      DEP is associated with prohibitive MM, thereby identifying patient cohorts that
      may be unsuitable for BPG.

PMID- 20141960
TI  - Functional status as a prognostic factor for primary revascularization for
      critical limb ischemia.
AB  - BACKGROUND: Lower extremity arterial revascularization (LEAR) is the gold
      standard for critical lower limb ischemia (CLI). The goal of this study was
      twofold. First, we evaluated the long-term functional status of patients
      undergoing primary LEAR for CLI. Second, prognostic factors of long-term
      functional status and survival after primary LEAR for CLI were assessed. METHODS:
      All primary LEAR procedures were analyzed. Patients were stratified by
      preoperative functional status: ambulatory (group I) vs nonambulatory (group II).
      Patients were followed-up after 3 and 6 years. Adverse events (AEs) were
      categorized according to predefined standards: minor, surgical, failed
      revascularization, and systemic. Associated patient demographic/clinical data
      were analyzed using univariate and multivariate methods. RESULTS: There were 106
      LEAR patients (group I: n = 42, 40% vs group II: n = 64, 60%). Group II patients
      were significantly older (75 vs 62 years; P = .00), were classified ASA 3-4 more
      frequently (78% vs 52%; P < .02), had more cardiac disease (n = 42, 66% vs n =
      10, 24%; P = .00), renal disease (n = 26, 41% vs n = 7, 17%; P = .00), diabetes
      (n = 36, 56% vs n = 8, 19%; P = .00), hypertension (n = 47, 73% vs n = 13, 31%; P
      = .00) and severe CLI (n = 42, 66% vs n = 18, 38%; P < .01). Group II patients
      had a higher incidence of death (65.6% vs 14.3%; P = .00), minor AEs (n = 38, 26%
      vs n = 10, 22%; P = .00), surgical AEs (n = 48, 33% vs n = 12, 26%; P < .02) and
      systemic AEs (n = 24, 86% vs n = 4, 9%; P < .02). Also more unplanned
      reinterventions occurred in group II (n = 148, 76% vs n = 47, 24%; P = .00).
      Nonambulatory status was a multivariate independent predictor of nonambulatory
      status after LEAR during 6 years follow-up (odds ration [OR[: 21.47; 95%
      confidence interval [CI]: 2.76-166.77; P = .00). Pulmonary disease (OR: 7.49; 95%
      CI: 2.17-25.80; P = .00), not prescribing beta-blockers (OR: 4.67; 95% CI: 1.28
      17.03; P < .02), nonambulatory status (OR: 22.99; 95% CI: 6.27-84.24; P = .00),
      and systemic AEs (OR: 9.66; 95% CI: 1.84-50.57; P < .01) were independent
      predictors of death. Functional status was not improved in group II after long
      term follow-up. CONCLUSION: Nonambulatory patients suffer from extensive comorbid
      conditions. They are accompanied with an increased occurrence of AEs, unplanned
      reinterventions, and poor long-term survival rates. Successful LEAR did not
      improve their functional status after 6 years. This emphasizes that attempts for
      limb salvage must be carefully considered in these patients.

PMID- 20141961
TI  - Invited commentary.

PMID- 20141962
TI  - Interventions for mesenteric vasculitis.
AB  - OBJECTIVE: This study reviewed the outcomes of open and endovascular
      revascularization for mesenteric vasculitis (MV). METHODS: We reviewed the
      clinical data of all patients who underwent revascularization for occlusive MV
      from 1984 to 2008. Patients treated for aneurysms or mucosal bleeding without
      ischemic symptoms were excluded. End points were early mortality and morbidity,
      survival, freedom from mesenteric symptoms, and patency. Outcomes of open
      reconstructions were compared with the results of 163 patients who underwent open
      operations for atherosclerotic disease. RESULTS: There were 15 patients (13
      females, 2 males) with a mean age of 38 years (range, 15-66 years). Etiologies
      were Takayasu's arteritis in 7, polyarteritis nodosa in 4, indeterminate in 3,
      and giant cell arteritis in 1. The celiac axis was affected in 13, superior
      mesenteric artery (SMA) in 13, renal arteries in 8, and the aorta in 4. Seven
      patients had active disease, and eight were in remission. Nine (60%) presented
      with symptomatic chronic (n = 8) and acute (n = 1) mesenteric ischemia. Six
      patients with asymptomatic disease underwent mesenteric revascularization during
      other aortic-based operations. Fourteen patients (93%) had 10 mesenteric bypasses
      (8 aortic based; 2 iliac), three had aortoplasties, of which two had mesenteric
      patch angioplasties, and one underwent arcuate ligament release with patch
      angioplasty. One patient (7%) underwent percutaneous transluminal angioplasty of
      SMA stenosis. There were no early deaths. Early complications occurred in three
      patients (20%) after open reconstruction, including gastrointestinal hemorrhage,
      ileus with re-exploration, and superior mesenteric vein thrombosis. Median follow
      up was 22 months. One graft thrombosis in a patient with active disease was
      treated with redo bypass 74 months after aorta-celiac-SMA bypass. All patients
      were alive at 10 years, with similar expected survival compared with the general
      population (P = .69). Compared with patients with atherosclerotic disease, open
      reconstructions for MV had similar freedom from mesenteric symptoms (83% vs 75%,
      P = .80) and similar primary graft patency (83% vs 84%, P = .9). CONCLUSION:
      Mesenteric vasculitis is a rare manifestation of Takayasu arteritis,
      polyarteritis nodosa, indeterminate, or giant cell arteritis. Open
      revascularization is durable and effective when needed.

PMID- 20141963
TI  - Invited commentary.

PMID- 20141964
TI  - Protective effects of cold spinoplegia with fasudil against ischemic spinal cord
      injury in rabbits.
AB  - OBJECTIVE: Paraplegia remains a serious complication after surgical repair of
      thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the
      neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing
      the number of infiltrating cells in the ventral horn and increasing the induction
      of eNOS against ischemic spinal cord injury in rabbits. METHODS: Eighteen
      Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4
      degrees C) and fasudil (group 2, n = 6, 4 degrees C) were immediately infused
      into the isolated segmental lumbar arteries over 30 seconds after aortic
      clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was
      evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia.
      Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles
      of endothelial nitric oxide synthase immunoreactivity were performed. The number
      of intact motor neuron cells and infiltrating cells in the ventral horn were
      compared. RESULTS: Two days after reperfusion, group 2 and group 3 showed better
      neurologic function, a greater number of intact motor neuron cells, and a smaller
      number of infiltrating cells in the ventral horn than group 1. The induction of
      endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after
      reperfusion in group 2. CONCLUSION: These results indicate that fasudil has
      neuroprotective effects against ischemic spinal cord injury in rabbits by
      reducing the number of infiltrating cells in the ventral horn and prolonging the
      expression of eNOS.

PMID- 20141965
TI  - Invited commentary.

PMID- 20141966
TI  - Thoracic endografting in a patient with hereditary hemorrhagic telangiectasia
      presenting with a descending thoracic aneurysm.
AB  - A 53-year-old woman with no classic risk factors for aneurysm disease presented
      with the sudden onset of chest pain and dyspnea. A large descending thoracic
      aortic aneurysm with focal type B dissection was identified and excluded by
      emergency thoracic endografting. Further postoperative evaluation revealed a
      history of epistaxis, perioral telangiectasias, hepatic hypervascularity, and a
      mutation in the gene expressing activin receptor-like kinase 1 (ALK1), leading to
      a diagnosis of hereditary hemorrhagic telangiectasia. Aortic aneurysms associated
      with hereditary hemorrhagic telangiectasia are extremely rare, and to our
      knowledge, this is the first report of thoracic endografting in this patient
      population.

PMID- 20141967
TI  - High spatial resolution magnetic resonance imaging of cystic adventitial disease
      of the popliteal artery.
AB  - High spatial resolution magnetic resonance imaging (MRI) of patients with cystic
      adventitial disease can demonstrate connections between cysts in the adventitia
      and the adjacent joint, which is important for successful treatment. The
      inability to identify these during surgery can lead to a recurrence; thus, high
      spatial resolution MRI has the potential to affect therapy. This article presents
      the high spatial resolution MRI findings of cystic adventitial disease in a
      series of three consecutive patients and discusses the relevance of these
      findings to the etiology and therapy.

PMID- 20141968
TI  - Do no harm.

PMID- 20141973
TI  - Shoulder, hip, knee, and PRP.

PMID- 20141969
TI  - Future of vascular surgery is in the office.
AB  - OBJECTIVE: The practice of vascular surgery is under pressure from various
      specialties and payers. Our group started office-based procedures in May 2007.
      This article reports our study of the effect of this change on our case volume,
      office revenue, and the financial impact on the health care system. METHODS:
      Between May 1, 2006, and April 30, 2007 (period 1), and between June 1, 2007, and
      May 31 2008 (period 2), 3041 and 3351 cases, respectively, were performed. In
      period 1, only venous cases could be done in the office. Before arteriogram,
      serum levels of urea nitrogen and creatinine were obtained. The number of
      percutaneous cases done in the hospital and office setting was analyzed, and
      revenue was calculated based on the 2008 Medicare fee schedule for our region.
      Amputation and mortality rates at 30 days were documented. Hospital DRG payment
      schedule was obtained. RESULTS: In period 1, 670 (22% of total) percutaneous
      procedures were performed compared with 1502 (44.8%) in period 2, a twofold
      increase. In period 1, 1.5% of total cases were done in the office compared with
      31% in period 2. There was a fivefold increase in revenue from these procedures.
      No deaths or amputations occurred as a result of procedures performed in the
      office. No anesthesiologist's expense and minimal preprocedural expenses were
      incurred. Total payment by Medicare, DRG payment to the hospital, and the
      physician component were higher in all the cases. CONCLUSIONS: A vascular surgery
      practice can benefit from office-based procedures. Procedures can be done safely.
      It results in an increase in the number of percutaneous procedures and revenue
      with a significant savings to the health care system. Surgeons can control their
      schedule. Every vascular surgeon should consider doing these procedures in
      office.

PMID- 20141974
TI  - What's cooking at the AANA learning center?

PMID- 20141975
TI  - Is there a role for arthroscopy in the treatment of osteoarthritis?

PMID- 20141976
TI  - Selection bias results in misinterpretation of randomized controlled trials on
      arthroscopic treatment of patients with knee osteoarthritis.

PMID- 20141977
TI  - The health care bill.

PMID- 20141978
TI  - All-arthroscopic Weaver-Dunn-Chuinard procedure with double-button fixation for
      chronic acromioclavicular joint dislocation.
AB  - PURPOSE: We described a novel all-arthroscopic technique of coracoclavicular
      ligament reconstruction and reported the early clinical and radiologic results of
      this procedure. METHODS: We performed all-arthroscopic coracoclavicular ligament
      reconstruction in 10 consecutive patients (8 men and 2 women; mean age, 41 years)
      with a symptomatic chronic and complete acromioclavicular (AC) joint dislocation
      (Rockwood type III or IV). Four patients had undergone surgery previously: two
      had initial pinning of the acute AC joint separation, and two had a subsequent
      Mumford procedure. The surgical technique, performed entirely by arthroscopy,
      consisted of (1) rerouting the coracoacromial ligament with a bone block
      harvested from the tip of the acromion in a socket created in the distal clavicle
      (Chuinard's modification of the Weaver-Dunn procedure) and (2) augmenting the
      reconstruction with 2 titanium buttons connected by a heavy suture in a 4-strand
      configuration (Double-Button fixation; Smith & Nephew Endoscopy, Andover, MA).
      Patients were prospectively followed up for a mean of 12.8 months (range, 6 to 20
      months). RESULTS: One patient had a superficial infection of the superior
      (clavicular) portal, which resolved with oral antibiotics. At the most recent
      review, all patients were satisfied or very satisfied with the cosmesis, and 9 of
      10 returned to previous sports, including contact and overhead sports. All
      symptoms resolved (pain, shoulder weakness, paresthesia). The mean postoperative
      University of California, Los Angeles modified AC rating score was 16.5 points
      (range, 13 to 18 points) out of 20 points. The mean Subjective Shoulder Value
      improved from 36% (range, 0% to 70%) preoperatively to 82.5% (range, 70% to 100%)
      postoperatively (P = .005). The bone block was totally healed in the medullary
      canal in 8 cases and partially healed in 2. No loss of reduction was observed in
      any of the patients. CONCLUSIONS: Our study shows that severe chronic symptomatic
      AC joint separations, defined as Rockwood types III through V, can be repaired
      entirely by arthroscopy safely and effectively by transferring the coracoacromial
      ligament with a bone block in the distal clavicle. The bone block transfer
      (Weaver-Dunn-Chuinard procedure) has the advantage of making the repair easier
      and stronger, and it provides bone-to-bone healing by use of free, autologous
      vascularized tissue. Double-Button fixation has the advantage of maintaining the
      reduction during the biological healing process. Although the durability of the
      reconstruction remains unproven, in our short-term follow-up we observed no loss
      of reduction and the functional and cosmetic results were uniformly good. LEVEL
      OF EVIDENCE: Level IV, therapeutic case series.

PMID- 20141979
TI  - The pattern and technique in the clinical evaluation of the adult hip: the common
      physical examination tests of hip specialists.
AB  - PURPOSE: The purpose of this study was to systematically evaluate the technique
      and tests used in the physical examination of the adult hip performed by multiple
      clinicians who regularly treat patients with hip problems and identify common
      physical examination patterns. METHODS: The subjects included 5 men and 6 women
      with a mean age (+/-SD) of 29.8 +/- 9.4 years. They underwent physical
      examination of the hip by 6 hip specialists with a strong interest in hip-related
      problems. All examiners were blind to patient radiographs and diagnoses. Patient
      examinations were video recorded and reviewed. RESULTS: It was determined that 18
      tests were most frequently performed (>or=40%) by the examiners, 3 standing, 11
      supine, 3 lateral, and 1 prone. Of the most frequently performed tests, 10 were
      performed more than 50% of the time. The tests performed in the supine position
      were as follows: flexion range of motion (ROM) (percentage of use, 98%), flexion
      internal rotation ROM (98%), flexion external rotation ROM (86%), passive supine
      rotation test (76%), flexion/adduction/internal rotation test (70%), straight leg
      raise against resistance test (61%), and flexion/abduction/external rotation test
      (52%). The tests performed in the standing position were the gait test (86%) and
      the single-leg stance phase test (77%). The 1 test in the prone position was the
      femoral anteversion test (58%). CONCLUSIONS: There are variations in the testing
      that hip specialists perform to examine and evaluate their patients, but there is
      enough commonality to form the basis to recommend a battery of physical
      examination maneuvers that should be considered for use in evaluating the hip.
      CLINICAL RELEVANCE: Patients presenting with groin, abdominal, back, and/or hip
      pain need to have a basic examination to ensure that the hip is not overlooked. A
      comprehensive physical examination of the hip will benefit the patient and the
      physician and serve as the foundation for future multicenter clinical studies.

PMID- 20141980
TI  - Cam impingement of the posterior femoral condyle in medial meniscal tears.
AB  - PURPOSE: The aim of this study was to compare the results of meniscal repair of
      the medial meniscus with or without decompression of the posterior segment of the
      medial meniscus for the treatment of posteromedial tibiofemoral incongruence at
      full flexion (PMTFI), which induces deformation of the posterior segment on
      sagittal magnetic resonance imaging (MRI). METHODS: For more than 2 years, we
      followed up 27 patients with PMTFI who were classified into the following 2
      groups. Group 1 included 8 patients (5 male joints and 3 female joints) with a
      medial meniscal tear with instability at the site of the tear who underwent
      meniscal repair. The mean age was 23.6 years. Group 2 included 19 patients (16
      male joints and 3 female joints) who had a meniscal tear with instability at the
      site of the tear and underwent meniscal repair and decompression. The mean age
      was 26.5 years. In decompression of the posterior segment, redundant bone tissue
      on the most proximal part of the medial femoral condyle was excised. The patients
      were assessed by use of the Lysholm score, sagittal MRI at full flexion, and
      arthroscopic examination. RESULTS: There were no statistical differences in mean
      Lysholm score between the 2 groups before surgery, but the mean score in group 2
      was significantly higher than that in group 1 after surgery. Meniscal deformation
      of the posterior segment at full flexion on MRI disappeared in all cases after
      decompression. On second-look arthroscopy, the rate of complete healing at the
      site of the tear was 0% in group 1 but 57% in group 2, and it was significantly
      different between these groups. CONCLUSIONS: The addition of decompression of the
      posterior segment of the medial meniscus to meniscal repair of knee joints with
      PMTFI allowed more room for the medial meniscus to accommodate and improved both
      function of the knee joint and the rate of success of repair of isolated medial
      meniscal tears in patients who regularly performed full knee flexion.

PMID- 20141981
TI  - Arbitrary starting point of separation affects morphology of the 2 bundles of
      anterior cruciate ligament at insertion sites.
AB  - PURPOSE: To explore whether changes in the starting point of separation affect
      the morphology of the 2 bundles of the anterior cruciate ligament (ACL) at
      insertion. METHODS: Ten cadaveric knees were used to separate the ACL fibers into
      2 bundles from 3 different starting points that were located at the proximal one
      fifth, two fifths, and three fifths of the inter-bundle mark line. The dividing
      lines between the 2 bundles at insertion and the area of the anteromedial (AM)
      bundle resulting from these different separations were compared, with data
      collected in groups I, II, and III, respectively. RESULTS: The angle of the
      dividing line and the long axis of the femoral footprint was 67.24 degrees +/-
      11.94 degrees, 91.01 degrees +/- 11.16 degrees, and 116.03 degrees +/- 9.01
      degrees in groups I, II, and III, respectively, and the percentage of the AM
      bundle area in the whole femoral footprint was 38.64% +/- 5.55%, 52.22% +/-
      6.76%, and 65.09% +/- 4.53%, respectively. At the tibial insertion sites, the
      angle between the dividing line and the sagittal plane was 110.17 degrees +/-
      13.26 degrees, 127.72 degrees +/- 8.94 degrees, and 149.28 degrees +/- 18.80
      degrees in groups I, II, and III, respectively, and the percentage of the AM
      bundle area in the whole footprint was 25.72% +/- 3.82%, 40.41% +/- 3.73%, and
      60.56% +/- 6.59%, respectively. There were statistical differences between the
      angle and the area data of each of the 2 groups at either the tibial or femoral
      insertion site. CONCLUSIONS: In an anatomic study of the ACL, changes in the
      point from which separation started resulted in noticeably different bundle
      morphology at the insertion. CLINICAL RELEVANCE: Proper separation will lead to a
      more accurate bundle description and, thus, a more accurate location of the
      tunnels in ACL reconstruction.

PMID- 20141982
TI  - The effect of medial meniscectomy and meniscal allograft transplantation on knee
      and anterior cruciate ligament biomechanics.
AB  - PURPOSE: Our purpose was to evaluate the effect of meniscectomy and meniscal
      allograft transplant on anterior cruciate ligament (ACL) and knee biomechanics.
      METHODS: A differential variable reluctance transducer was placed in the ACL of
      10 human cadaveric knees to record strain. Tibial displacement from a neutral
      reference was recorded relative to the position of the femur. Testing was
      performed at 30 degrees, 60 degrees, and 90 degrees of knee flexion. Six cycles
      of anterior-posterior loads were applied to the limit of 150 N. After a testing
      cycle, a medial meniscectomy was performed and the testing cycle was repeated. A
      meniscal allograft transplant was performed, and a final testing cycle was
      conducted. ACL strain and tibial displacement in the meniscectomy and meniscal
      allograft states were compared with the intact-knee state. RESULTS: Tibial
      displacement after meniscectomy significantly increased at all angles. The
      meniscal allograft transplant restored tibial displacement to normal values at 30
      degrees and 90 degrees. ACL strain increased significantly after meniscectomy at
      60 degrees and 90 degrees of flexion, and meniscal allograft transplant returned
      the strain values to normal at 60 degrees and 90 degrees. CONCLUSIONS: In most
      cases medial meniscectomy produced a significant increase in tibial displacement
      relative to the femur, and meniscal allograft transplantation restored
      displacement values to normal. Meniscectomy increased ACL strain and meniscal
      allograft transplant restored strain values to normal in 2 of 3 tested flexion
      angles. CLINICAL RELEVANCE: The absence of the medial meniscus exposes the ACL to
      increased strain, whereas meniscal allograft lowered the strain on the native
      ACL. This could have implications for those patients undergoing ACL
      reconstruction who have concomitant removal of the medial meniscus.

PMID- 20141983
TI  - Anatomic double-bundle anterior cruciate ligament reconstruction: kinematics and
      knee flexion angle-graft tension relation.
AB  - PURPOSE: The purpose of this study was to compare the bundle tension curves and
      resultant knee kinematics between 2 tensioning protocols in anatomic double
      bundle anterior cruciate ligament (ACL) reconstruction. METHODS: Anatomic double
      bundle ACL reconstruction was performed in 7 male cadaveric knees. Each graft was
      tensioned to 22 N under 2 conditions: (1) both bundles tensioned at 20 degrees of
      knee flexion (20/20 protocol) or (2) posterolateral (PL) bundle tensioned at 15
      degrees and anteromedial (AM) bundle at 45 degrees (45/15 protocol). Knee
      kinematics were recorded in response to anterior and combined rotatory loads in
      the intact, ACL-deficient, and reconstructed states. Bundle tension was recorded
      dynamically with knee motion and during each loading test. RESULTS: Tensioning
      both bundles at 20 degrees of knee flexion resulted in a reciprocal bundle
      tension pattern that was not statistically different; the PL bundle tension was
      greater than the AM bundle tension in full extension, and the AM bundle tension
      was greater than the PL bundle tension from 25 degrees to 120 degrees. In the
      second tensioning protocol, the AM bundle tension was significantly greater than
      the PL bundle tension at all flexion angles. Both tensioning protocols restored
      normal knee kinematics. CONCLUSIONS: Bundle-tensioning protocol is a variable
      that has a significant effect on the bundle-loading patterns in double-bundle ACL
      reconstruction. The 20/20 protocol resulted in AM and PL bundle-loading patterns
      that were equivalent during dynamic testing, whereas the 45/15 protocol led to
      excessive tension in the AM bundle in full extension. We recommend equal
      tensioning of both bundles with the knee at 20 degrees of flexion to restore
      relatively normal tension curves in each bundle and to avoid excessive stress on
      the AM bundle. CLINICAL RELEVANCE: In double-bundle ACL reconstruction, there is
      no consensus regarding bundle-tensioning protocols. This study provides data on
      the individual bundle tension curves that result from 2 commonly used tensioning
      protocols. These data will assist clinicians as the technique and application of
      double-bundle ACL reconstruction move forward.

PMID- 20141984
TI  - Graft tension during active knee extension exercise in anatomic double-bundle
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to measure graft tension in vivo in
      anatomic double-bundle anterior cruciate ligament (ACL) reconstruction during
      active knee extension, as well as to investigate the effect of loading a weight
      around the ankle on graft tension. METHODS: Seven patients with chronic ACL
      injury underwent anatomic double-bundle ACL reconstruction. Two grafts were
      temporarily fixed to the 2 tension-adjustable force gauges on the anterior tibial
      cortex, after they were fixed on the femur. After the creep within the femur-ACL
      graft-tibia construct was removed, 10 N of the initial tension was applied to
      each graft at 20 degrees. First, tension to the anteromedial (AM) and
      posterolateral (PL) grafts was continuously measured during passive extension
      from 90 degrees to 0 degrees with the patient under general anesthesia. Then,
      after the patient was awoken from anesthesia, graft tension was again recorded
      while the knee was actively extended by the patient in the same manner. Finally,
      after a 2-kg weight was placed around the ankle, the tension of each graft was
      measured again during active knee extension by the patient himself or herself.
      RESULTS: During passive extension motion, the tension of the AM graft was 19.3 +/
      4.7 N, whereas that of the PL graft was 24.5 +/- 5.9 N at 0 degrees. The tension
      of each graft increased when approaching full extension. During active knee
      extension motion, the tension of the AM graft was 24.0 +/- 6.1 N, whereas that of
      the PL graft was 30.8 +/- 7.3 N at 0 degrees. When the 2-kg weight was placed
      around the ankle during active motion, the tension was significantly higher than
      that with no weight at all flexion angles. CONCLUSIONS: Graft tension was greater
      during active motion than that during passive motion, and graft tension during
      active motion increased with a weight placed around the ankle. The highest graft
      tension was 62.8 N at 0 degrees of flexion with a 2-kg weight placed around the
      ankle, when 20 N of initial tension was applied at 20 degrees of flexion in
      anatomic double-bundle ACL reconstruction. Thus care must be taken during active
      extension exercise with weights, especially in the first few weeks after ACL
      reconstruction, because graft tension increases with an increase in initial
      tension and easily reaches a critical level. CLINICAL RELEVANCE: Our findings
      suggest that active knee extension exercise should be performed in moderation in
      the early phase after ACL reconstruction.

PMID- 20141985
TI  - Remnant posterior cruciate ligament-augmenting stent procedure for injuries in
      the acute or subacute stage.
AB  - PURPOSE: To evaluate the results of a remnant posterior cruciate ligament (PCL)
      augmenting stent procedure for acute- or subacute-stage PCL injuries in terms of
      stability and clinical results. METHODS: Between September 2003 and March 2006,
      32 patients with a PCL tear underwent a reconstructive stent procedure with an
      autogenous hamstring tendon graft to augment the remains of the injured PCL. Of
      these patients, 20 who satisfied our inclusion criteria and could be followed up
      for a minimum duration of 24 months were enrolled in our study. The remnant PCL
      and synovium were preserved, and augmentation was performed by use of the
      transtibial technique. A femoral tunnel was created near the footprint of the
      anterolateral bundle. Stability was measured on posterior stress radiographs and
      by use of a maximum manual displacement test performed with a KT-1000 arthrometer
      (MEDmetric, San Diego, CA). The International Knee Documentation Committee (IKDC)
      and Orthopadische Arbeitsgruppe Knie scoring systems were used for clinical
      evaluation. RESULTS: Stress radiographs showed that the mean side-to-side
      differences in displacement were reduced from 9.9 +/- 4.0 mm preoperatively to
      3.0 +/- 2.6 mm at the last follow-up, whereas KT-1000 tests showed that these
      differences were reduced from 6.9 +/- 2.1 mm preoperatively to 2.7 +/- 1.5 mm.
      The final IKDC score was A in 7 patients (35%), B in 10 (50%), C in 2 (10%), and
      D in 1 (5%). The mean Orthopadische Arbeitsgruppe Knie score improved from 61.6
      +/- 13.1 to 88.2 +/- 9.5. CONCLUSIONS: Of the patients, 90% showed satisfactory
      posterior stability and 85% had a normal or nearly normal rating based on the
      IKDC score at a mean of 3 years after the remnant PCL-augmenting stent procedure
      in the acute or subacute stage of PCL injuries.

PMID- 20141986
TI  - Arthroscopic subtalar arthrodesis using a posterior 2-portal approach in the
      prone position.
AB  - PURPOSE: The purpose of this study was to evaluate the results of posterior
      arthroscopic subtalar arthrodesis (ASTA) by use of a posterior 2-portal approach
      in the prone position and to describe the surgical technique. METHODS: Between
      September 2004 and December 2006, posterior ASTA was performed in 16 patients
      (all men) with post-traumatic subtalar arthritis after an intra-articular
      fracture of the calcaneus. The mean age was 44 years (range, 20 to 64 years). The
      mean follow-up period was 30 months (range, 20 to 46 months). According to the
      Sanders classification of calcaneal fractures, 2 patients had type IIA fractures,
      3 had type IIIB fractures, 6 had type IIIAC fractures, and 5 had type IIIBC
      fractures. The technique involved using posteromedial and posterolateral portals
      in the prone position, posterior talocalcaneal facet debridement, and
      percutaneous posterior fixation with 2 cannulated screws. Clinical results were
      evaluated by use of the ankle-hindfoot scale of the American Orthopaedic Foot &
      Ankle Society (AOFAS), the Angus and Cowell scoring system, and postoperative
      complications. To assess union rate and time to union, radiographic evaluations
      were also performed. RESULTS: The mean modified AOFAS score (maximum, 94 points)
      improved from 35 points (range, 24 to 45 points) preoperatively to 84 points
      (range, 71 to 94 points) at final follow-up. According to the Angus and Cowell
      criteria, 13 patients had a good rating, 2 had a fair rating, and 1 had a poor
      rating because of nonunion. The union rate was 94% at a mean of 11 weeks, and
      nonunion occurred in 1 case. No other postoperative complications occurred.
      CONCLUSIONS: ASTA in the prone position through a posterior 2-portal approach
      provided safe access and superior visualization of the posterior talocalcaneal
      facet and easy fixation of posterior screws. This technique also provided good
      clinical outcomes (good results in 81% of patients according to the Angus and
      Cowell scoring system and a mean modified AOFAS score of 84 points) and a 94%
      union rate at a mean of 11 weeks.

PMID- 20141987
TI  - Arthroscopic stabilization for first-time versus recurrent shoulder instability.
AB  - PURPOSE: The purpose of this study was to systematically review the evidence on
      the outcomes of arthroscopic repair for anterior shoulder instability in first
      time dislocators when compared with patients with recurrent instability. METHODS:
      We designed a systematic review with a specific methodology to investigate the
      outcomes of surgery for those with only a first-time dislocation versus those who
      underwent surgery after multiple instability events. We performed a literature
      search from January 1966 to December 2008 using Medline, CINAHL (Cumulative Index
      to Nursing and Allied Health Literature), and the Cochrane Central Register of
      Controlled Trials. Key words included the following: first time, primary
      shoulder, or recurrent shoulder instability, shoulder dislocation, Bankart
      repair, arthroscopic Bankart repair, and labral repair. The inclusion criteria
      were cohort studies (Level I to II) that evaluated the outcomes of patients
      undergoing arthroscopic stabilization after the first dislocation or multiple
      recurrent episodes. Studies that lacked a comparison group or were retrospective
      (Level III studies or higher) were excluded. RESULTS: There were 15 studies that
      met the inclusion criteria and were included in the final analysis: 5 in the
      first-time dislocation group and 10 in the recurrent instability group. Study
      design, patient demographics, mean number of dislocations, surgical technique,
      and rehabilitation protocol, as well as subjective and objective outcome
      measures, were recorded. CONCLUSIONS: There were no differences in recurrence or
      complication rate among patients undergoing surgery after the primary dislocation
      when compared with those undergoing surgery after multiple recurrent episodes.
      Clinical outcome measures significantly improved within all independent studies
      from preoperatively to postoperatively. However, because of variation in the
      outcome measurement tools used, no direct comparison between the study groups
      could be performed. Additional randomized controlled studies are needed to
      compare the functional outcome, quality of life, and ability to return to
      preinjury activity level among patients undergoing early versus delayed repair
      for anterior shoulder instability.

PMID- 20141988
TI  - Consensus statement on shoulder instability.
AB  - The understanding and treatment of shoulder instability comprise a rapidly
      evolving area of interest in orthopaedics. Evaluation methods are becoming more
      specific in showing the exact pathologies causing the symptoms. Magnetic
      resonance arthrography and arthroscopy have contributed to this development. The
      patient with an unstable shoulder should be thoroughly evaluated through their
      history and specific clinical tests of the shoulder as well as the
      scapulothoracic joint. Often, shoulder instability can be classified after this
      primary evaluation. Magnetic resonance arthrography and arthroscopy are the gold
      standards in soft-tissue evaluation, whereas specialized radiographic
      examinations and computed tomography scans are used to assess bony defects.
      Patients are treated according to the pathology found on preoperative or
      pretreatment evaluation. Multiple factors need to be considered before the
      treatment program is instituted, including the patient's age, activity demands,
      associated pathology and dysfunction, soft-tissue pathology, degree of
      instability, direction, frequency, and etiology. Treatment can be nonoperative or
      arthroscopic or open repair. Soft-tissue pathology and bony defects should be
      addressed, and the surgeon's preferred method and skills are important in
      choosing the right treatment for the patient. The patient should be informed
      about possible complications, restrictions during the treatment period, and the
      prognosis for the particular type of instability. To improve progress in shoulder
      orthopaedics, one of the most important factors can be a universal agreement on
      an outcome measurement tool that is well designed and validated.

PMID- 20141989
TI  - Re: The rotator crescent and rotator cable: an anatomic description of the
      shoulder's "suspension bridge".

PMID- 20141990
TI  - Anatomic single- and double-bundle anterior cruciate ligament reconstruction
      flowchart.
AB  - Anatomy is the foundation of orthopaedic surgery, and the advancing knowledge of
      the anterior cruciate ligament (ACL) anatomy has led to the development of
      improved modern reconstruction techniques that approach the anatomy of the native
      ACL. Current literature on the anatomy of the ACL and its reconstruction
      techniques, as well as our surgical experience, was used to develop a flowchart
      that can aid the surgeon in performing anatomic ACL reconstruction. We define
      anatomic ACL reconstruction as the functional restoration of the ACL to its
      native dimensions, collagen orientation, and insertion sites. A guideline was
      written to accompany this flowchart with more detailed information on anatomic
      ACL reconstruction and its pitfalls, all accompanied by relevant literature and
      helpful figures. Although there is still much to learn about anatomic ACL
      reconstruction methods, we believe this is a helpful document for surgeons. We
      continue to modify the flowchart as more information about the anatomy of the
      ACL, and how to more closely reproduce it, becomes available.

PMID- 20141991
TI  - The use of platelet-rich plasma in arthroscopy and sports medicine: optimizing
      the healing environment.
AB  - Platelet-rich plasma (PRP) is a new technology focused on enhancing the healing
      response after injury of different tissue types. PRP is prepared by withdrawal of
      patients' peripheral blood and centrifugation to obtain a highly concentrated
      sample of platelets, which undergo degranulation to release growth factors with
      healing properties. It also contains plasma, cytokines, thrombin, and other
      growth factors that are implicated in wound healing and have inherent biological
      and adhesive properties. The prepared concentrate is then injected back into the
      patient at the site of morbidity. This may be intralesional, intra-articular, or
      surrounding the involved tissue bed. PRP preparations have been used
      therapeutically in various medical fields from implantology to vascular ulcers,
      with a more recent evolution and promising results in the field of sports
      medicine and arthroscopy. Sports medicine patients desire a rapid return to their
      preinjury level of function, and PRP may have certain applications that will
      speed recovery in cases of tendon, ligament, muscle, and cartilage disorders. In
      particular, anterior cruciate ligament reconstruction has shown better autograft
      maturation, improved donor site morbidity, and pain control, in addition to
      improved allograft incorporation. By acceleration of the biological integration
      of the graft by use of PRP, patients may undergo faster, more intensive
      rehabilitation programs and return to sports more rapidly. Because of its
      autogenous origin, easy preparation, and excellent safety profile, the advent of
      PRP has opened another therapeutic door for sports medicine physicians and
      orthopaedic surgeons. Future directions of PRP include improving the results of
      arthroscopic and related surgery, in addition to delineating correct dosage,
      timing, and quantification, as well as ideal techniques of PRP application.

PMID- 20141992
TI  - Minimally invasive bone grafting of cysts of the femoral head and acetabulum in
      femoroacetabular impingement: arthroscopic technique and case presentation.
AB  - Femoroacetabular impingement (FAI) has been recently established as a risk factor
      in the development of osteoarthritis of the hip. Intraosseous cysts are commonly
      seen on imaging of FAI. In most cases these cysts are incidental and do not
      require specific treatment at the time of surgical treatment of hip impingement.
      However, in some cases the cysts may mechanically compromise the acetabular rim
      or femoral neck. We present a technique for treating such cysts with an all
      arthroscopic technique using a commercially available bone graft substitute
      composed of cancellous bone and demineralized bone matrix placed within an
      arthroscopic cannula for direct delivery into the cysts. This technique may be of
      benefit to surgeons treating FAI with an all-arthroscopic technique.

PMID- 20141993
TI  - Proper insertion angle is essential to prevent intra-articular protrusion of a
      knotless suture anchor in shoulder rotator cuff repair.
AB  - The advent of new arthroscopic devices has led to the development of novel
      techniques of arthroscopic rotator cuff repair. However, failure to recognize
      specific technical aspects and improper application of these devices can lead to
      complications. We report a case of intra-articular protrusion of knotless anchors
      (PEEK PushLock SP, 4.5 x 18.5 mm; Arthrex, Naples, FL), used in the lateral row
      of a suture-bridging technique for arthroscopic rotator cuff repair. This case
      draws attention to the increased length of such devices when compared with
      traditional suture anchors, the technical aspects of proper device use, the
      possible patient-related factors such as implant-patient size mismatch, and the
      importance of additional imaging for the investigation of failure to progress
      postoperatively.

PMID- 20141994
TI  - [Eisenmenger syndrome. Why should we intervene early?].

PMID- 20141995
TI  - [Eisenmenger syndrome. Epidemiology and natural history].
AB  - Eisenmenger syndrome is the last-stage of congenital heart diseases with
      untreated left to right shunt. Tolerance and prognosis are better than with
      idiopathic pulmonary hypertension. However, patients follow-up is often performed
      in inappropriate non-specialized care centres which makes the collection of
      epidemiological data difficult. Consequently, population registries are necessary
      and would increase knowledge of natural history. Finally, complications are often
      multiple and unexpected with lack of specialized management. Such patients
      require expert supervision with a multidisciplinary approach in experienced and
      specialized centres.

PMID- 20141996
TI  - [Eisenmenger syndrome. Conventional treatments and general management].
AB  - Eisenmenger syndrome is a multisystem disorder, which evolves to severe
      complications in adult patients. It is recommended that patients be referred to a
      center with expertise in the fields of pulmonary hypertension and congenital
      heart disease. General measures include education of patients, avoidance of
      strenuous physical activity, pregnancy and infections, and careful intraoperative
      monitoring during noncardiac surgery. Conventional therapies for these patients
      are based on clinical experience rather than evidence based data. Phlebotomies
      should be reserved for patients with moderate-to severe hyperviscosity symptoms
      (usually when haematocrit is > 65 %). The use of oxygen therapy is controversial,
      but sometimes might improve symptoms. Oral anticoagulants are also controversial
      and can be used in patients with pulmonary thrombosis and without haemoptysis.
      Transplantation is restricted to highly symptomatic patients with poor prognosis.
      Novel disease targeting therapy may delay the need for transplantation for these
      patients.

PMID- 20141997
TI  - [Eisenmenger syndrome. Specific treatments].

PMID- 20141998
TI  - [Eisenmenger syndrome. Role of rare diseases reference centers in the management
      of pulmonary hypertension in congenital heart diseases].

PMID- 20141999
TI  - [Eisenmenger syndrome. Competence centers for adults and children with pulmonary
      hypertension: practical experience].

PMID- 20142000
TI  - [Eisenmenger syndrome. Pathophysiology].
AB  - Eisenmenger syndrome is the most feared complication by patients with congenital
      heart disorders with left-to-right shunt. This complication became rare in
      industrial countries thanks to optimized perinatal patient management and
      precocious elimination of the shunt. The presence of endothelial circulatory
      cells is a poor prognosis factor.

PMID- 20142001
TI  - [Eisenmenger syndrome. Transition structure].

PMID- 20142003
TI  - Spontaneous dissection of the superior mesenteric artery.
AB  - We describe a case of spontaneous dissection and thrombosis of the superior
      mesenteric artery in a 54-year-old man who presented with new onset of
      hypertension and epigastric pain. Initial unsuccessful treatment with catheter
      directed thrombolysis was followed by surgical intervention. In cases in which an
      extensive intimectomy is performed, early institution of antiplatelet therapy or
      anticoagulation may be necessary to preserve vessel patency due to the presence
      of a prothrombotic surface and compromised outflow.

PMID- 20142002
TI  - Vein wall remodeling after deep vein thrombosis: differential effects of low
      molecular weight heparin and doxycycline.
AB  - BACKGROUND: Venous thrombus resolution sets up an early intense inflammatory
      reaction, from which vein wall damage results. Tissue response to injury includes
      matrix metalloproteinase (MMP) activation and extracellular matrix protein
      turnover. This study sought to determine the effect of exogenous MMP inhibition
      and its potential attenuation of early vein wall injury. METHODS: Rats received
      treatment beginning 24 hr after a stasis venous thrombosis by near occlusive
      ligation and until harvest at day 7. Three groups were evaluated: (1) vehicle
      saline controls (NaCl), (2) low molecular weight heparin (LMWH; Lovenox, 3 mg/kg
      daily SQ), and (3) doxycycline (DOXY, 30 mg/kg daily PO). Thrombus size (mg/mm),
      levels of tumor necrosis factor alpha (TNF alpha) and D-dimer by colorimetric
      assay, and monocytes counts by immunohistochemistry were assessed. Vein wall
      assessment included stiffness by tensiometry, interleukin 1beta (IL-1 beta
      protein levels by enzyme-linked immunosorbent assay, MMP2 and -9 by zymography,
      and histological analysis of intimal thickness (IT). Comparisons were by t-test
      to control. p < 0.05 was considered significant. RESULTS: Thrombus sizes were
      similar at days 2 and 7 for all three groups, while thrombus TNFalpha was
      increased in 2-day LMWH- and DOXY-treated groups (NaCl = 1.0 +/- 0.8, LWMH = 9 +/
      3, DOXY = 27 +/- 5 pg/mg protein, n = 6-8, p < 0.05) and at 7 days in the DOXY
      group (NaCl = 3.0 +/- 2.5, DOXY = 23 +/- 4.2 pg/mg protein, n = 5, p < 0.05).
      Vein wall stiffness at 7 days was less with LMWH treatment, but not with DOXY,
      compared to controls (NaCl = 0.33 +/- 0.05, LMWH = 0.17 +/- 0.03, DOXY = 0.43 +/-
      0.09 N/mm, n = 5-7, p < 0.05). Vessel-wall IL-1 beta was reduced only in the DOXY
      group at 7 days (NaCl = 26 +/- 3, LMWH = 38 +/- 17, DOXY = 6 +/- 3 pg/mg protein,
      n = 4-6, p < 0.05), as was the IT score versus controls (NaCl = 2.2 +/- 0.6, LMWH
      =1.7 +/- 0.3, DOXY = 0.8 +/- 0.20, n = 4-6, p < 0.05). Zymographic MMP9 activity
      was significantly reduced at 2 days in the LMWH and DOXY groups (NaCl = 85 +/-
      24, LMWH = 23 +/- 7( *), DOXY = 13 +/- 5 U/mg protein, n = 6-8, p < 0.05). MMP2
      zymographic activity, thrombus monocyte cell counts, and D-dimer activity were
      not significantly different across groups. CONCLUSION: Treatment with LMWH or
      DOXY did not alter the size of deep vein thrombosis, mildly altered thrombus
      composition, and differentially affected vein wall injury, despite similar
      reductions in early MMP9 activity. Whether exogenous MMP inhibition affects long
      term vein wall fibrosis will require further study.

PMID- 20142004
TI  - Safety and efficacy of therapeutic angiogenesis as a novel treatment in patients
      with critical limb ischemia.
AB  - BACKGROUND: In some patients with critical limb ischemia (CLI) the possibility of
      revascularizing treatment does not exist. In this case therapeutic angiogenesis
      (TA) using autologous endothelial progenitor cell (EPC) transplantation could be
      an alternative. The objective of our study was to evaluate the safety and
      efficacy of TA using EPC. METHODS: Twenty-eight patients with CLI who were not
      candidates for surgical or endovascular revascularization were included in a
      prospective study. To mobilize EPCs from the bone marrow, granulocyte colony
      stimulating growth factor was injected subcutaneously at doses of 5 microg/kg/day
      for 5 days. Apheresis was performed, obtaining 50 mL of blood with a high rate of
      EPCs (CD34(+) and CD133(+) cells were counted). EPCs were implanted in the
      ischemic limb by intramuscular injections. Primary end points were the safety and
      feasibility of the procedure and limb salvage rate for amputation at 12 months.
      Other variables studied were improvement in rest pain, healing of ulcers, ankle
      brachial pressure index (ABI), and digital plethysmography. All procedures were
      done pretreatment and every 3 months for a year on average. Postransplantation
      arteriography was done in selected cases. RESULTS: No adverse effects were
      observed. Mean follow-up was 14 months. Before treatment, mean basal ABI was
      0.35+/-0.2 and at 18 months postimplantation, 0.72+/-0.51 (p=0.009). There was a
      mean decrease of five points in pain scale: basal 8.7+/-1, after TA 3.8+/-2.9
      (p=0.01). Seven patients required major amputation. Kaplan-Meier analysis
      revealed a limb salvage rate of 74.4% after 1 year. CONCLUSION: Implantation of
      EPCs in CLI is a safe alternative, improves tissue perfusion, and obtains high
      amputation-free rates. Nevertheless, this is a small cohort and results should be
      tested with long randomized trials.

PMID- 20142005
TI  - Lithium does not protect against spinal cord ischemia-reperfusion injury in
      rabbits.

PMID- 20142006
TI  - Gateway to the world of hand therapy.

PMID- 20142007
TI  - Training grip control with a Fitts' paradigm: a pilot study in chronic stroke.
AB  - STUDY DESIGN: A clinical measurement study. PURPOSE: To test the applicability of
      Fitts' paradigm to grasping tasks in individuals with chronic stroke.
      INTRODUCTION: Fitts' Law relates the time of target achievement to task
      difficulty in repetitive motor tasks. METHODS: Six male chronic stroke patients
      performed repetitive actuation of a grip force dynamometer with their affected
      hands for 12 sessions over four to six weeks. RESULTS: Movement times followed
      Fitts' behavior with correlations of R(2)>0.8 for all subjects. Grasp control
      improved during training, as indicated by an average decrease in Fitts' slope of
      26% at high difficulty levels (p<0.05), and decreases in the number of force
      corrections and in jerkiness, both at p<0.001 level. CONCLUSIONS: The Fitts' grip
      force targeting protocol provides an objective standardized instrument for grasp
      proficiency quantification and a potentially efficacious platform for hand
      training for persons with stroke. LEVEL OF EVIDENCE: N/A.

PMID- 20142008
TI  - Treatment of grade III thumb metacarpophalangeal ulnar collateral ligament
      injuries with early controlled motion using a hinged splint.
AB  - Ulnar collateral ligament (UCL) injuries of the thumb metacarpophalangeal (MCP)
      joint are some of the more common injuries to the thumb and are usually treated
      with immobilization. There are benefits, however, to early active motion for
      healing ligaments. Therefore, these authors incorporated some of the concepts
      related to early controlled motion and its role in healing, and created a hinged
      thumb MCP radial and ulnar deviation restriction splint for use with Grade III
      UCL injuries.

PMID- 20142009
TI  - A review of clinical tests and signs for the assessment of ulnar neuropathy.
      Goldman SB, Brininger TL, Schrader JW, Koceja DM. J Hand Ther. 2009;22:209-19.

PMID- 20142011
TI  - ASHT President's Lecture: Making decisions using values, experience, and
      evidence.

PMID- 20142012
TI  - Clinical myology at the crossroads; the gospel truth.

PMID- 20142019
TI  - Prognosis of stage A or B heart failure patients with elevated B-type natriuretic
      peptide levels.
AB  - BACKGROUND: Heart failure (HF) patients have a poor prognosis, yet outcomes might
      be improved by early identification of risk. We investigated the prognostic value
      of B-type natriuretic peptide (BNP) in patients at risk for HF (American College
      of Cardiology [ACC]/American Heart Association [AHA] HF Stages A and B), and
      compared prognosis with Stage C/D patients. METHODS AND RESULTS: Outpatients
      referred for echocardiogram (n=829) were stratified by ACC/AHA HF stage and BNP
      levels (cutpoint of 100pg/mL). Primary outcome was death or cardiac
      hospitalization at 1 year. BNP levels increased with increasing numbers of
      cardiovascular risk factors and with HF stage. Stage A/B patients with high BNP
      had a similar or worse prognosis than Stage C/D patients with low BNP. In fact,
      the prognosis of Stage C/D patients with low BNP did not significantly differ
      from the prognosis of Stage A/B patients with low BNP (adjusted HR 1.21, 95% CI
      0.62-2.37), whereas Stage A/B patients with high BNP did have a significantly
      worse prognosis (adjusted HR 1.91, 95% CI 1.11-3.28). CONCLUSIONS: Individuals
      without any history of HF but with BNP >or=100pg/mL are at equal or higher risk
      than those with a HF history whose BNP is <100pg/mL. BNP may be useful to
      identify asymptomatic individuals at high risk for future cardiovascular events.

PMID- 20142022
TI  - Endothelial function and arterial compliance are not impaired in subjects with
      heart failure of non-ischemic origin.
AB  - BACKGROUND: Patients with heart failure and underlying ischemic heart disease
      (IHD) exhibit both endothelial dysfunction and increased arterial stiffness. We
      investigated whether this is also the case in heart failure of nonischemic
      etiology. METHODS AND RESULTS: Eleven patients with heart failure and IHD, 12
      patients with heart failure from angiographically verified idiopathic nonischemic
      dilated cardiomyopathy (DCM), and 16 healthy subjects of similar age and sex were
      compared. Endothelium-dependent and independent function were evaluated by
      ultrasonic measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate
      (GTN)-induced dilatation of the brachial artery respectively. Vascular compliance
      was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index
      (AIx). Heart failure severity was similar in IHD and DCM patients. FMD was
      impaired in the subjects with IHD as compared with control subjects (4.8 +/- 0.3
      vs. 8.0 +/- 3.6 %, P < .01), but not in those with DCM. GTN-induced
      vasodilatation was not different in patients and controls. PWV was also increased
      in IHD patients compared with controls (12.1 +/- 3.6 vs. 8.0 +/- 1.6 m/s, P <
      .01), but not in DCM patients. AIx was similar in patients and controls.
      CONCLUSION: Heart failure of nonischemic etiology is not associated with
      abnormalities of endothelium-mediated dilatation or of arterial compliance. The
      findings of our study now need to be confirmed in larger studies.

PMID- 20142021
TI  - Patient expectations from implantable defibrillators to prevent death in heart
      failure.
AB  - BACKGROUND: Indications for implantable cardioverter-defibrillators (ICDs) in
      heart failure (HF) are expanding and may include more than 1 million patients.
      This study examined patient expectations from ICDs for primary prevention of
      sudden death in HF. METHODS AND RESULTS: Study participants (n = 105) had an EF
      <35% and symptomatic HF, without history of ventricular tachycardia/fibrillation
      or syncope. Subjects completed a written survey about perceived ICD benefits,
      survival expectations, and circumstances under which they might deactivate
      defibrillation. Mean age was 58, LVEF 21%, 40% were New York Heart Association
      Class III-IV, and 65% already had a primary prevention ICD. Most patients
      anticipated more than10 years survival despite symptomatic HF. Nearly 54%
      expected an ICD to save >or=50 lives per 100 during 5 years. ICD recipients
      expressed more confidence that the device would save their own lives compared
      with those without an ICD (P < .001). Despite understanding the ease of
      deactivation, 70% of ICD recipients indicated they would keep the ICD on even if
      dying of cancer, 55% even if having daily shocks, and none would inactivate
      defibrillation even if suffering constant dyspnea at rest. CONCLUSIONS: HF
      patients anticipate long survival, overestimate survival benefits conferred by
      ICDs, and express reluctance to deactivate their devices even for end-stage
      disease.

PMID- 20142020
TI  - Left ventricular remodeling and myocardial recovery on mechanical circulatory
      support.
AB  - BACKGROUND: Myocardial recovery after ventricular assist devices (VAD) is rare
      but appears more common in nonischemic cardiomyopathies (NICM). We sought to
      evaluate left ventricular (LV) end diastolic diameter (LVEDD) for predicting
      recovery after VAD. METHODS AND RESULTS: NICM patients receiving long-term
      mechanical support between 1996 and 2008 were reviewed. Subjects were divided
      into 3 groups: mild, moderate, and severe dilation (Group A: LVEDD <6.0 cm [n =
      22]; Group B: 6.0-7.0 cm [n = 32]; Group C: >7.0 cm [n = 48], respectively).
      Overall, recovery (successful explant without transplantation) occurred in 14 of
      102 subjects (14%). Of these, 2 died and 2 required transplantation within 1
      year. Recovery was more common in patients without LV dilation (Groups A/B/C =
      32%/22%/0%, P < .001), as was sustained recovery (alive and transplant free 1
      year after explant; A/B/C = 27%/10%/0%, P = .001). Of the recovery patients in
      Group A, 6/7 (86%) had sustained recovery versus 3/6 (50%) in Group B.
      CONCLUSIONS: Recovery occurred in 32% of NICM patients without significant LV
      dilation at time of VAD, the majority of whom experienced significant sustained
      recovery. Recovery was not evident in those with severe LV dilation. Routine
      echocardiography at the time of implant may assist in targeting patients for
      recovery after VAD.

PMID- 20142023
TI  - Long-term outcomes with ambrisentan monotherapy in pulmonary arterial
      hypertension.
AB  - BACKGROUND: This study evaluated long-term outcomes in patients with pulmonary
      arterial hypertension (PAH) undergoing treatment with ambrisentan monotherapy, a
      selective oral endothelin-1 receptor antagonist. METHODS AND RESULTS: Patients
      who participated in the Ambrisentan in Pulmonary Arterial Hypertension: A Phase
      3, Randomized, Double-Blind, Placebo-Controlled Multicenter Efficacy Study (ARIES
      1) clinical trial and extension phase at our institution were included. Cardiac
      catheterization, 6-minute walk distance (6MWD), and cardiac magnetic resonance
      (MRI) data were retrospectively reviewed. Twelve patients with PAH (11
      idiopathic, 1 fenfluramine) had follow-up from 3 to 5.5 years from the initiation
      of ARIES-1. Patients received ambrisentan therapy throughout the study period and
      were on ambrisentan monotherapy for the first 2 years. At year 1, improvements in
      median mean pulmonary arterial pressure (PA), cardiac output, and pulmonary
      vascular resistance (PVR) were seen (P = .02, P = .03, P < .01), and the
      improvement in PVR persisted at 2 years. 6MWD also improved significantly between
      baseline (350 m) and 1 and 2 years (397 m, P < .01 and 393 m, P = .01). Cardiac
      MRI results were more varied, with an increase in RV ejection fraction from 29%
      at baseline to 46% at 2 years (P = .02), but other MRI variables did not improve.
      CONCLUSIONS: Ambrisentan monotherapy led to improvements in catheterization,
      6MWD, and RV ejection fraction, and shows promise as a long-term treatment for
      pulmonary arterial hypertension.

PMID- 20142024
TI  - Baseline plasma NT-proBNP and clinical characteristics: results from the
      irbesartan in heart failure with preserved ejection fraction trial.
AB  - BACKGROUND: N-terminal B type natriuretic peptide (NT-proBNP) is usually elevated
      in heart failure (HF) patients with reduced ejection fraction (EF). Less is known
      about NT-proBNP in HF with preserved EF (HF-PEF). We measured baseline NT-proBNP
      in 3562 HF-PEF enrolled patients in the Irbesartan in Heart Failure with
      Preserved Ejection Fraction trial. METHODS AND RESULTS: Patients with EF >or=45%,
      age >or=60 years, and either New York Heart Association (NYHA) II-IV symptoms
      with HF hospitalization (HFH) within 6 months or NYHA III-IV symptoms with
      corroborative evidence of HF or structural changes associated with HF-PEF. NT
      proBNP (pg/mL) measured centrally using the Elecsys proBNP assay (Roche). Mean
      age 72 +/- 7 years, 60% were women, the investigator indicated HF etiology was
      hypertension in 64%; the majority were in NYHA III. Medications included
      diuretics in 82%, angiotensin-converting enzyme inhibitor in 26%, beta-blocker in
      59%, and spironolactone in 15%. Median NT-proBNP was 341 pg/mL (interquartile
      range 135 to 974 pg/mL) and geometric mean was 354 pg/mL. In multivariate
      analysis, the baseline characteristics most strongly associated with higher NT
      proBNP levels were atrial fibrillation (ratio of geometric mean 2.59, P < .001),
      NYHA IV symptoms (1.52, P < .001), lower estimated glomerular filtration rate
      (1.44, P < .001), and HFH hospitalization within 6 months (1.37, P < .001).
      CONCLUSIONS: Most HF-PEF patients have elevated NT-proBNP levels. The NT-proBNP
      concentrations were related to baseline characteristics generally associated with
      worse outcomes for HF patients.

PMID- 20142025
TI  - The impact of perceived adverse effects on medication changes in heart failure
      patients.
AB  - BACKGROUND: Given the importance of patient safety and well-being, we quantified
      the likelihood and type of medication changes observed after 5 possible adverse
      effects (AE) perceived by heart failure (HF) patients. METHODS AND RESULTS: We
      conducted a retrospective cohort study using 18 months follow-up data from the
      Coordinating study evaluating Outcomes of Advising and Counseling in HF study on
      754 patients previously hospitalized for HF (NYHA II-IV, mean age 70 years). Data
      used for this secondary analysis included problem checklists that patients had
      completed at 3 points in time, and medication data collected from chart review.
      Changes in potential causal cardiovascular medication and relevant alleviating
      medication were classified. Within group and relative risks (RR) for medication
      changes were calculated. Of the 754 patients, 50% reported dizziness, 44% dry
      cough, 19% nausea, 19% diarrhea, and 12% gout on the first checklist. Overall,
      the likelihood of a medication change was increased by 38% after a perceived AE.
      Dry cough had the highest increased likelihood of an associated cardiovascular
      medication change (RR 1.83, CI 1.35-2.49). Patients reporting gout had a four
      fold higher likelihood of alleviating medication started or intensified.
      CONCLUSIONS: A considerable number of HF patients perceived possible AE. However,
      the likelihood of medication being changed after a possible AE was rather low.
      There seems to be room for improving the management of AE.

PMID- 20142027
TI  - Patients' self-assessed functional status in heart failure by New York Heart
      Association class: a prognostic predictor of hospitalizations, quality of life
      and death.
AB  - BACKGROUND: Clinician-assigned New York Heart Association (NYHA) class is an
      established predictor of outcomes in heart failure. This study aims to test
      whether patients' self-assessment of functional status by NYHA class predicts
      hospital admissions, quality of life, and mortality. METHODS AND RESULTS: This
      was an observational study within a randomized controlled trial. A total of 293
      adult patients diagnosed with heart failure were recruited after an emergency
      admission at 3 acute hospitals in Norfolk, UK. Outcome measures included number
      of emergency admissions over 6 months, self-assessed quality of life measured
      with the Minnesota Living with Heart Failure questionnaire (MLHFQ) and EQ-5D at 6
      months, and deaths up to 20 months' follow-up. Patients were grouped into 3 NYHA
      groups (I/II, III, and IV) based on patients' self-assigned NYHA class (SA-NYHA).
      A Poisson model indicated an increased readmission rate associated with higher SA
      NYHA class (adjusted rate ratio 1.21; 95% CI 1.04-1.41; P=.02). Higher SA-NYHA
      class at baseline predicted worse quality of life at 6 months' follow-up (P=.002
      for MLHFQ; P=.047 for EQ-5D), and was associated with higher mortality rate
      (adjusted hazard ratio 1.84; 95% CI 1.10-3.06; P=.02). CONCLUSIONS: SA-NYHA class
      is predictive of hospitalization, quality of life, and mortality among patients
      with heart failure.

PMID- 20142028
TI  - Plasma ACE2 activity is an independent prognostic marker in Chagas' disease and
      equally potent as BNP.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) 2 is a novel homologue of ACE. It
      metabolizes angiotensin (Ang)II to Ang-(1-7). This study aims to investigate the
      diagnostic and prognostic potency of circulating ACE2 activity in patients with
      heart failure (HF) from Chagas' disease (CD). METHODS AND RESULTS: Blood samples
      were obtained from 111 CD patients and 40 age- and gender-matched healthy
      subjects. The CD patients were further subdivided according to their New York
      Heart Association classification. ACE2 activity was significantly increased in CD
      patients with HF, but not in patients without systolic dysfunction. Moreover,
      plasma ACE2 activity was significantly correlated with their clinical severity
      and echocardiographic parameters. Importantly, the potency of circulating ACE2
      activity in CD patients was equally potent as that of B-type natriuretic peptide
      to predict cardiac death and heart transplant. Most importantly, patients with
      both parameters elevated were on a 5-fold higher risk to reach an endpoint than
      patients with increase in only 1 of the 2 parameters. CONCLUSIONS: Determination
      of ACE2 activity may provide a new and important diagnostic and prognostic marker
      for patients with CD. ACE2 activity and BNP concentration have additive
      predictive value and may be used in combination to offer a new dimension of
      prediction in HF.

PMID- 20142026
TI  - Medication adherence is a mediator of the relationship between ethnicity and
      event-free survival in patients with heart failure.
AB  - BACKGROUND: Rehospitalization rates are higher in African American than Caucasian
      patients with heart failure (HF). The reasons for the disparity in outcomes
      between African Americans and Caucasians may relate to differences in medication
      adherence. To determine whether medication adherence is a mediator of the
      relationship between ethnicity and event-free survival in patients with HF.
      METHODS AND RESULTS: Medication adherence was monitored longitudinally in 135 HF
      patients using the Medication Event Monitoring System. Events (emergency
      department visits for HF exacerbation, HF and cardiac rehospitalization, and all
      cause mortality) were obtained by interview and hospital data base review. A
      series of regression models and survival analyses was conducted to determine
      whether medication adherence mediated the relationship between ethnicity and
      event-free survival. Event-free survival was significantly worse in African
      Americans than Caucasians. Ethnicity was a predictor of medication adherence
      (P=.011). African Americans were 2.57 times more likely to experience an event
      than Caucasians (P=.026). Ethnicity was not a predictor of event-free survival
      after entering medication adherence in the model (P=.06). CONCLUSIONS: Medication
      adherence was a mediator of the relationship between ethnicity and event-free
      survival in this sample. Interventions designed to reduce barriers to medication
      adherence may decrease the disparity in outcomes.

PMID- 20142029
TI  - Sleep-disordered breathing and heart failure: focus on obstructive sleep apnea
      and treatment with continuous positive airway pressure.
AB  - BACKGROUND: Among patients with heart failure, sleep-disordered breathing is a
      common problem, with a prevalence ranging from 24% to 76%. Encompassed within the
      general category of sleep-disordered breathing are 2 types of sleep apnea:
      obstructive sleep apnea (OSA) occurs when the oropharyngeal musculature relaxes,
      causing a collapse of the upper airway, and central sleep apnea occurs when the
      brain stem fails to stimulate breathing. METHODS AND RESULTS: This article
      focuses on the relationship between heart failure and OSA, the treatment of OSA
      with continuous positive airway pressure (CPAP), and the role of CPAP in
      improving such effects of heart failure as ejection fraction, blood pressure,
      sympathetic activity, sleepiness, heart rate, and mortality. CONCLUSIONS: It is
      important to distinguish the type of sleep-disordered breathing a patient may
      have. Further studies are needed to elucidate the effects of CPAP and other
      therapies.

PMID- 20142031
TI  - Targacept's NNR drugs rehabilitate nicotine.

PMID- 20142030
TI  - Influence of rapid fluid loading on airway structure and function in healthy
      humans.
AB  - BACKGROUND: The present study examined the influence of rapid intravenous fluid
      loading (RFL) on airway structure and pulmonary vascular volumes using computed
      tomography imaging and the subsequent impact on pulmonary function in healthy
      adults (n = 16). METHODS AND RESULTS: Total lung capacity (DeltaTLC = -6%),
      forced vital capacity (DeltaFVC = -14%), and peak expiratory flow (DeltaPEF = 
      19%) decreased, and residual volume (DeltaRV = +38%) increased post-RFL (P <
      .05). Airway luminal cross-sectional area (CSA) decreased at the trachea, and at
      airway generation 3 (P < .05), wall thickness changed minimally with a tendency
      for increasing in generation five (P = .13). Baseline pulmonary function was
      positively associated with airway luminal CSA; however, this relationship
      deteriorated after RFL. Lung tissue volume and pulmonary vascular volumes
      increased 28% (P < .001) post-RFL, but did not fully account for the decline in
      TLC. CONCLUSIONS: These data suggest that RFL results in obstructive/restrictive
      PF changes that are most likely related to structural changes in smaller airways
      or changes in extrapulmonary vascular beds.

PMID- 20142033
TI  - A new age for MAGL.
AB  - Monoacylglycerol lipase (MAGL) has been known for its participation in
      triacylglycerol breakdown and endocannabinoid deactivation. Now Nomura et al.
      show that cancer cells can hijack MAGL to produce oncogenic lipid messengers.
      This exciting finding raises important pathophysiological questions.

PMID- 20142032
TI  - On-bead library screening made easier.
AB  - In this issue of Chemistry & Biology, Astle et al. report the rapid
      identification of the most active hits from a large one-bead-one-compound peptoid
      library by magnetic sorting and without the need for labor-intensive resynthesis
      of the hits.

PMID- 20142034
TI  - Mechanism-based neddylation inhibitor.
AB  - Brownell et al. (2010) elucidate the mechanism of action of MLN4924, a NEDD8
      activating enzyme inhibitor. MLN4924 requires the activity of the enzyme to
      generate a NEDD8-adenylate analog that potently and selectively shuts down this
      posttranslational modification system.

PMID- 20142035
TI  - A tale of two metals.
AB  - A recent study by Thomas O'Halloran and his group at Northwestern University
      (Avarez et al. Sciencexpress, www.scienceexpress.org, 26 November 2009) has
      provided insights into how tetrathiomolybdate inhibits copper-trafficking
      proteins through metal cluster formation. The broader context of the work
      provides an attractive explanation of the long recognized but poorly understood
      antagonistic effects of Mo and Cu in living organisms.

PMID- 20142036
TI  - The switch regulating transcription of the Escherichia coli biotin operon does
      not require extensive protein-protein interactions.
AB  - Transcription of the Escherichia coli biotin (bio) operon is regulated by BirA, a
      protein that is not only the repressor that regulates bio operon expression by
      DNA binding but also the enzyme that covalently attaches biotin to its cognate
      acceptor proteins. Binding of BirA to the bio operator requires dimerization of
      the protein that is triggered by BirA-catalyzed synthesis of biotinoyl-adenylate
      (bio-AMP), the obligatory intermediate of the attachment reaction. The current
      model postulates that the unmodified acceptor protein binds the monomeric
      BirA:bio-AMP complex and thereby blocks assembly (dimerization) of the form of
      BirA that binds DNA. We report that expression of fusion proteins that carry
      synthetic biotin-accepting peptide sequences was as effective as the natural
      acceptor protein in derepression of bio operon transcription. These peptide
      sequences have sequences that are remarkably dissimilar to that of the natural
      acceptor protein, and our data thus argue that the regulatory switch does not
      require the extensive protein-protein interactions postulated in the current
      model.

PMID- 20142037
TI  - ITZ-1, a client-selective Hsp90 inhibitor, efficiently induces heat shock factor
      1 activation.
AB  - ITZ-1 is a chondroprotective agent that inhibits interleukin-1beta-induced matrix
      metalloproteinase-13 (MMP-13) production and suppresses nitric oxide-induced
      chondrocyte death. Here we describe its mechanisms of action. Heat shock protein
      90 (Hsp90) was identified as a specific ITZ-1-binding protein. Almost all known
      Hsp90 inhibitors have been reported to bind to the Hsp90 N-terminal ATP-binding
      site and to simultaneously induce degradation and activation of its multiple
      client proteins. However, within the Hsp90 client proteins, ITZ-1 strongly
      induces heat shock factor-1 (HSF1) activation and causes mild Raf-1 degradation,
      but scarcely induces degradation of a broad range of Hsp90 client proteins by
      binding to the Hsp90 C terminus. These results may explain ITZ-1's inhibition of
      MMP-13 production, its cytoprotective effect, and its lower cytotoxicity. These
      results suggest that ITZ-1 is a client-selective Hsp90 inhibitor.

PMID- 20142038
TI  - Biosynthesis of rhizocticins, antifungal phosphonate oligopeptides produced by
      Bacillus subtilis ATCC6633.
AB  - Rhizocticins are phosphonate oligopeptide antibiotics containing the C-terminal
      nonproteinogenic amino acid (Z)-l-2-amino-5-phosphono-3-pentenoic acid (APPA).
      Here we report the identification and characterization of the rhizocticin
      biosynthetic gene cluster (rhi) in Bacillus subtilis ATCC6633. Rhizocticin B was
      heterologously produced in the nonproducer strain Bacillus subtilis 168. A
      biosynthetic pathway is proposed on the basis of bioinformatics analysis of the
      rhi genes. One of the steps during the biosynthesis of APPA is an unusual aldol
      reaction between phosphonoacetaldehyde and oxaloacetate catalyzed by an aldolase
      homolog RhiG. Recombinant RhiG was prepared, and the product of an in vitro
      enzymatic conversion was characterized. Access to this intermediate allows for
      biochemical characterization of subsequent steps in the pathway.

PMID- 20142039
TI  - Seamless bead to microarray screening: rapid identification of the highest
      affinity protein ligands from large combinatorial libraries.
AB  - Several approaches have been developed for screening combinatorial libraries or
      collections of synthetic molecules for agonists or antagonists of protein
      function, each with its own advantages and limitations. In this report, we
      describe an experimental platform that seamlessly couples massively parallel bead
      based screening of one-bead one-compound combinatorial libraries with microarray
      based quantitative comparisons of the binding affinities of the many hits
      isolated from the bead library. Combined with other technical improvements, this
      technique allows the rapid identification of the best protein ligands in
      combinatorial libraries containing millions of compounds without the need for
      labor-intensive resynthesis of the hits.

PMID- 20142040
TI  - Toward the rational design of p53-stabilizing drugs: probing the surface of the
      oncogenic Y220C mutant.
AB  - The p53 cancer mutation Y220C induces formation of a cavity on the protein's
      surface that can accommodate stabilizing small molecules. We combined fragment
      screening and molecular dynamics to assess the druggability of p53-Y220C and map
      ligand interaction sites within the mutational cavity. Elucidation of the binding
      mode of fragment hits by crystallography yielded a clear picture of how a drug
      might dock in the cavity. Simulations that solvate the protein with isopropanol
      found additional sites that extend the druggable surface. Moreover, structural
      observations and simulation revealed the dynamic landscape of the cavity, which
      improves our understanding of the impact of the mutation on p53 stability. This
      underpins the importance of considering flexibility of the cavity in screening
      for optimized ligands. Our findings provide a blueprint for the design of
      effective drugs that rescue p53-Y220C.

PMID- 20142041
TI  - Deciphering the late biosynthetic steps of antimalarial compound FR-900098.
AB  - FR-900098 is a potent chemotherapeutic agent for the treatment of malaria. Here
      we report the heterologous production of this compound in Escherichia coli by
      reconstructing the entire biosynthetic pathway using a three-plasmid system.
      Based on this system, whole-cell feeding assays in combination with in vitro
      enzymatic activity assays reveal an unusual functional role of nucleotide
      conjugation and lead to the complete elucidation of the previously unassigned
      late biosynthetic steps. These studies also suggest a biosynthetic route to a
      second phosphonate antibiotic, FR-33289. A thorough understanding of the FR
      900098 biosynthetic pathway now opens possibilities for metabolic engineering in
      E. coli to increase production of the antimalarial antibiotic and combinatorial
      biosynthesis to generate novel derivatives of FR-900098.

PMID- 20142042
TI  - Deacetylase inhibitors dissociate the histone-targeting ING2 subunit from the
      Sin3 complex.
AB  - Histone deacetylase (HDAC) inhibitors are in clinical development for several
      diseases, including cancers and neurodegenerative disorders. HDACs 1 and 2 are
      among the targets of these inhibitors and are part of multisubunit protein
      complexes. HDAC inhibitors (HDACis) block the activity of HDACs by chelating a
      zinc molecule in their catalytic sites. It is not known if the inhibitors have
      any additional functional effects on the multisubunit HDAC complexes. Here, we
      find that suberoylanilide hydroxamic acid (SAHA), the first FDA-approved HDACi
      for cancer, causes the dissociation of the PHD-finger-containing ING2 subunit
      from the Sin3 deacetylase complex. Loss of ING2 disrupts the in vivo binding of
      the Sin3 complex to the p21 promoter, an important target gene for cell growth
      inhibition by SAHA. Our findings reveal a molecular mechanism by which HDAC
      inhibitors disrupt deacetylase function.

PMID- 20142043
TI  - Activation of the NRF2 signaling pathway by copper-mediated redox cycling of para
      and ortho-hydroquinones.
AB  - Transcription factor NF-E2 p45-related factor 2 (Nrf2) mediates adaptation to
      oxidants and electrophiles through up-regulating genes that contain antioxidant
      response elements (AREs) in their promoters. Using the stably transfected human
      AREc32 reporter cell line, we found that copper and other transition metals
      enhanced induction of ARE-driven luciferase by 2-tert-butyl-1,4-hydroquinone
      (tBHQ) as a result of increased oxidation to 2-tert-butyl-1,4-benzoquinone (tBQ).
      Following exposure to tBHQ for 30 min, ARE-luciferase activity measured after 24
      hr was dependent on the presence of Cu(2+). In contrast, tBQ-induced activity was
      Cu(2+)-independent. The metal-catalyzed oxidation of tBHQ to tBQ occured rapidly
      and stoichiometrically. Compounds that share para- or ortho-hydroquinone
      structures, such as catechol estrogens, dopamine, and l-DOPA, also induced ARE
      driven luciferase in a Cu(2+)-dependent manner. Thus, the oxidation of para- and
      ortho-hydroquinones to quinones represents the rate-limiting step in the
      activation of Nrf2.

PMID- 20142045
TI  - The National Marrow Donor Program's symposium on patient advocacy in cellular
      transplantation therapy: addressing barriers to hematopoietic cell
      transplantation.
AB  - Although hematopoietic cell transplantation (HCT) is an effective treatment
      option for patients with life-threatening blood, immune system, or genetic
      disorders, many barriers besides a lack of suitably matched donors exist and can
      have an adverse impact on access and outcomes of HCT. In 2008, the National
      Marrow Donor Program, through its Office of Patient Advocacy, convened a diverse
      group of experts and transplantation survivors to identify persistent patient
      barriers throughout the transplantation process and to make recommendations for
      programs and initiatives to address these barriers, including new research
      opportunities. This group included transplantation physicians and other health
      care providers, relevant subject experts, and representatives from
      transplantation centers and patient advocacy organizations. Working groups were
      formed to identify patient barriers to HCT and to recommend and prioritize
      initiatives as they relate to the pretransplantation period, the early
      posttransplantation period, long-term survivorship, financial issues, and special
      populations. This report summarizes the symposium's deliberations and
      recommendations to address persistent patient barriers throughout the
      transplantation process.

PMID- 20142046
TI  - Falling chimerism after reduced intensity conditioning transplantation.

PMID- 20142044
TI  - Methionine aminopeptidases from Mycobacterium tuberculosis as novel
      antimycobacterial targets.
AB  - Methionine aminopeptidase (MetAP) is a metalloprotease that removes the N
      terminal methionine during protein synthesis. To assess the importance of the two
      MetAPs in Mycobacterium tuberculosis, we overexpressed and purified each of the
      MetAPs to near homogeneity and showed that both were active as MetAP enzymes in
      vitro. We screened a library of 175,000 compounds against MtMetAP1c and
      identified 2,3-dichloro-1,4-naphthoquinone class of compounds as inhibitors of
      both MtMetAPs. It was found that the MtMetAP inhibitors were active against
      replicating and aged nongrowing M. tuberculosis. Overexpression of either
      MtMetAP1a or MtMetAP1c in M. tuberculosis conferred resistance of bacterial cells
      to the inhibitors. Moreover, knockdown of MtMetAP1a, but not MtMetAP1c, resulted
      in decreased viability of M. tuberculosis. These results suggest that MtMetAP1a
      is a promising target for developing antituberculosis agents.

PMID- 20142047
TI  - Enhanced xanthine oxidoreductase expression and tissue nitrate reduction in germ
      free mice.
AB  - The nitrate-nitrite-NO pathway is emerging as an alternative to the l-arginine/NO
      synthase pathway for the generation of NO in mammals. Bioactivation of the stable
      nitrate anion involves initial reduction to nitrite by commensal bacteria in the
      gastrointestinal tract. Nitrite is then further metabolized in blood and tissues
      to form nitric oxide (NO) and other bioactive nitrogen oxides. In addition to
      nitrate reduction by bacteria, a functional mammalian nitrate reductase activity
      was recently explored. It was demonstrated that xanthine oxidoreductase (XOR) and
      possibly other enzymes can catalyze nitrate reduction under normoxic conditions
      in vivo. In the present study, we compared nitrate reduction in germ free (GF)
      and conventional mice. One aim was to see if the complete lack of bacterial
      nitrate reduction in the GF mice would be associated with an upregulation of
      mammalian nitrate reductase activity. Sodium nitrate (NaNO(3)) or placebo (NaCl)
      was injected intraperitoneally and blood and tissues were collected 1.5-2h later
      for measurements of nitrate and nitrite and in some cases analyses of protein
      expression. Tissue and plasma levels of nitrate increased to a similar extent in
      conventional and GF animals after nitrate administration. Plasma nitrite was 3
      fold higher in GF mice receiving nitrate compared to placebo while this effect of
      nitrate was absent in the conventional mice. In GF mice pretreated with the
      xanthine oxidase inhibitor allopurinol the increase in nitrite was attenuated.
      The levels of nitrite in the liver and small intestine increased after the
      nitrate load in GF mice but not in the conventional mice. Anaerobic nitrate
      reduction to nitrite in intestinal tissue homogenates was also accelerated in GF
      mice. Studies of tissue protein levels revealed increased expression of XOR in
      the livers of GF animals. We conclude that XOR expression in tissues is enhanced
      in germ free mice and this may explain the apparently greater tissue nitrate
      reductase activity observed in these animals. Future studies will reveal if this
      represents a compensatory functional response to uphold nitrite homeostasis in
      the absence of commensal bacteria.

PMID- 20142049
TI  - [Pathophysiology and management of Peyronie's disease in adult patients: an
      update].
AB  - Peyronie's disease (PD) is due to a fibrotic plaque forms in the tunica albuginea
      layer of the penis. It is responsible of penile pain, angulation, and erectile
      dysfunction. Even though the aetiology remains unknown, the knowledge of the
      pathophysiology has evolved in recent years. Recent studies indicate that PD has
      prevalence of 3 to 9% in adult men. During the initial acute phase (6 to 18
      months), the condition may progress, stabilize or regress in 20%. Therefore, a
      conservative treatment approach has been advocated. An initial discussion about
      evaluation, information, and reassurance is necessary in most cases. The most
      commonly employed oral therapies include tocopherol (vitamin E), and para
      aminobenzoate (Potaba), which have failed to demonstrate efficiency.
      Intralesional injection therapies with interferon alpha-2B, verapamil are
      frequently used as a first-line treatment modality, and can provide an
      improvement in decreasing penile pain and penile curvature. Current literature
      has shown that extracorporeal shock wave lithotripsy was only active on the pain.
      Regarding penile curvature, there are discrepancies in the published series. The
      surgical approach is restricted to men unresponsive to nonoperative therapies
      (i.e., 10% of patients). In such cases, plication, grafting or even penile
      prosthesis implantation are conceivable management options.

PMID- 20142048
TI  - [Prostate cancer: medicoeconomic aspects].
AB  - Prostate cancer is the first cancer in men. Its incidence is constantly
      increasing. The significant evolution of diagnostic and therapeutic means during
      the two last decades contrasts with the scarcity of medicoeconomic studies. The
      aim of this review is to present a synthesis of the different studies published
      and to respond to questions about the economic aspects of this disease, with the
      evaluation of its direct and indirect costs. The cost-effectiveness and the
      benefits of the prevention and the screening are still being studied. The costs
      of the surgery and the radiotherapy are roughly similar. The new surgical
      techniques, especially the laparoscopic and the robotic surgeries, are not
      necessarily associated with higher costs, in condition of a high-volume
      laparoscopic surgery program and a faster discharge. The indirect costs of
      prostate cancer concern the loss of economic production associated with the
      disease and death and are more difficult to determine.

PMID- 20142050
TI  - [Recommendations of the Infectious Disease Committee of the French Association of
      Urology (AFU): antibiotic prophylaxis for urological procedures].
AB  - The French Association of anesthesiology (SFAR) has published in 1999 the
      Antibiotic prophylaxis guidelines. Antibiotic resistance has increased and new
      procedures appeared so new recommendations were needed. We present the antibiotic
      prophylaxis guidelines from the committee of infectious diseases of the French
      Association of Urology.

PMID- 20142051
TI  - [First line indications for hormonal therapy in prostate cancer].
AB  - The utilization of androgen deprivation therapy in prostate cancer has evolved
      over time. Unquestionably considered first line treatment in metastatic cancers
      or in case of lymph node involvement, it is increasingly used in locally advanced
      and high-risk cancers, combined with radiation therapy. However, the practical
      modalities of treatment are still controversial (neoadjuvant,
      concomitant/adjuvant) and should be discussed on a case-by-case basis, taking
      into account tumor stage and risk level, which depends mainly on Gleason score
      and PSA levels and kinetics. Hormone therapy is also indicated in case of
      systemic relapse, especially if PSA doubling time is less than 12 months. LHRH
      agonists have become the standard care; antiandrogens can be added at the
      beginning of the LHRH agonist therapy to obtain a complete androgen blockade.
      Intermittent androgen deprivation therapy has recently proved efficacious and
      might be more widely used in the future, provided that strict prescription and
      follow-up recommendations are clearly established.

PMID- 20142052
TI  - [Laparoscopic radical prostatectomy in the elderly (>75 years old): oncological
      and functional results].
AB  - OBJECTIVE: Prostate cancer incidence increases with age. Radical prostatectomy
      (RP) seems to be feasible for elderly well-selected patients. We report our
      experience with patients older than 75 years old who underwent laparoscopic RP.
      METHODS: From 2000 to 2007, 22 patients older than 75 years old at time of
      surgery were included in the study. The patient clinical characteristics, the
      peri- and postoperative data, and the pathological data were collected
      retrospectively. The overall, specific and PSA-free survival were analysed with
      Kaplan-Meier method. The functional results such as continence and erectile
      function were assessed by self-questionnaires. RESULTS: The mean patient age was
      75 years (75-81), the median PSA level was 10.77 ng/ml (5-30). The mean American
      Society of Anesthesiologists score was 2.1 (2-3). Two (9%) perioperative
      complications occurred but no conversion was necessary. Five patients (23%) had a
      pT3 disease and the overall positive surgical margins rate was 14%. With a median
      follow-up of 42 months, no patient has died and five had a biochemical
      recurrence. At 12-month follow-up, 82% of patients were continent (no pad) and
      potency (erection sufficient for intercourse) rate was 36% with or without the
      use of phosphodiesterase-5 inhibitors. CONCLUSION: Laparoscopic RP is feasible
      for localized prostate cancer in elderly well-selected patients with satisfactory
      oncological and functional outcomes although the incontinence rate is increased
      comparing to younger patients.

PMID- 20142053
TI  - [MRI and prostatic cancer: measurements of kinetic perfusion parameters of
      gadolinium with a computerized-aided diagnostic tool (CAD)].
AB  - OBJECTIVES: To assess with a CAD in the peripheral (ZP) and transitional (ZT)
      zones the areas with modifications of the kinetic parameter Kep (ratio of
      exchanges between vascular compartment and extravascular extracellular spaces) in
      prostatic cancers with DCE MRI before radical prostatectomy. METHODS: Forty-two
      consecutive patients (mean age 67 years, mean PSA: 8.9 ng/ml) with a prostatic
      cancer proved after a set of 12 biopsies underwent, before radical prostatectomy,
      a dynamic MRI (1.5T) with a surface coil after injection of gadolinium. We look
      with a CAD for foci of voxels with an abnormal Kep in ZP and/or in ZT. Foci of
      abnormal voxels computerized were compared with histological results of radical
      prostatectomies: prostates were shared in 12 sectors (six peripheral and six
      central) and a total of 504 sectors were studied. The links between prostatic
      capsule and foci of voxels with elevated Kep were systematically evaluated. The
      location and the local extension of the various cancerous foci were estimated. A
      comparison with the results of the T2W and T1 DCE MRI sequences without use of
      the CAD was made. RESULTS: Eighty-eight percent of investigated patients revealed
      at least a cancerous focus associated with a group of pathological voxels.
      Hundred and seventy-eight of the 504 investigated prostatic sectors revealed a
      cancerous lesion after radical prostatectomy (RP) and 116 a focus of voxels with
      a pathological Kep being linked to 71 isolated lesions, some of them filling
      several sectors (47 peripheral and 24 transitional). The automatic research with
      the software of foci of voxels with a parameter Kep more than 2,2 per minute to
      detect a cancerous lesion had a sensitivity by sector less than the reading
      without CAD (69% in ZP and 58% in ZT against respectively, 85 and 66% (p<0.01)
      but seemed more specific: 98% in PZ and 95% in ZT against respectively, 80 and
      82% (p<0.01). After RP, 16 cancers were classified Pt2, 10 Pt2R+ and 16 Pt3. The
      CAD had a better accuracy (74%) than T2W MRI (60%) to look for an extracapsular
      extension (EPE) or a risk of positive margins: 86% of extraprostatic extension
      and 60% of positive margins were near a focus of pathological voxels.
      CONCLUSIONS: CAD allowed a computerized qualitative and quantitative study of DCE
      MRI. It identified and localized with a good specificity the significant foci. A
      focus of voxels with elevated Kep against the capsule increased significantly the
      risk of an extraprostatic extension or a positive margin after radical
      prostatectomy.

PMID- 20142054
TI  - [Predictive factors and long term carcinogenic results of patients who no longer
      have residual tumors (stage pT0) on specimens of total cystectomy carried out for
      cancer of the bladder].
AB  - AIM: The aim of our study was to evaluate predictive factors and long-term
      carcinogenic results for patients who had had a total cystectomy for cancer of
      the bladder and whose final histological results did not show evidence of a
      residual tumor. PATIENTS AND METHODS: From 1988 to 2002, 192 patients had a total
      cystectomy for a bladder tumor. No residual tumor (pT0) was evident in the
      specimens of cystectomy of 22 patients (11.5%). None of the patients had distant
      metastasis or ganglions at the time of the initial examination. RESULTS:
      Predictive factors for having no residual tumors based on the specimen of
      cystectomy (pT0) were an antecedent of neo-adjuvant chemotherapy (p=0.0079), an
      interval between the resection of the bladder and the cystectomy of more than 12
      weeks (p=0.0014) and a resection of the initial bladder considered complete
      (p=0.0036). The average treatment of these 22 patients was 70+/-46 months. During
      treatment, two patients (9%) had a recurrence in the pelvis and 10 patients died
      including one from the development of his cancer of the bladder. Global, specific
      and non-recurrence survival at five years were 75%, 100% and 94%, respectively.
      We revealed better specific survival (p=0.0007) and without relapse (p<0.0001) in
      patients who no longer had a tumor on the specimen of cystectomy (pT0) compared
      with patients who had a residual tumor (pT+) but with no difference in global
      survival (p=0.0574). CONCLUSION: The absence of residual tumors (pT0) on a
      specimen of total cystectomy for cancer of the bladder was a good factor for
      prognosis regarding long-term survival even if tumor development was observed.
      Complete resection and neo-adjuvant chemotherapy probably played a beneficial
      role in the future of these patients.

PMID- 20142055
TI  - [Management of lithiasis of kidney transplant].
AB  - INTRODUCTION: Urolithiasis in kidney transplants is rare but not exceptional
      (0,20-3%). Dealing with it is complex: abstention, lithotripsy or surgery? The
      aim of this study is to find out what can be done about it. METHOD: A
      retrospective study about 420 kidney transplants performed in our institution
      between 1990 et 2005 revealed nine cases of lithiasis. Among the factors leading
      to lithiasis were urinary flow obstruction in six cases and hyperparathyroidy in
      three cases. RESULTS: Five grafts with calculi whose diameter do not exceed 5mm
      were kept under medical supervision. Two of them were in chronic rejection
      without residual diuresis. Extra shockwawe lithotripsy was performed for a 13 mm
      diameter calical calculi. Two percutaneous extraction were performed: one for a
      20mm diameter "pyelic" calculi and one for three kidney stones and among them one
      was 12 mm. A 20mm calculi was extracted by open pyelotomy during the repairing of
      the ureteral anastomosis on a Bricker diversion. CONCLUSION: Consequently,
      dealing with calculi on kidney transplants is similar to dealing with a unique
      native kidney.

PMID- 20142056
TI  - [Hydatid cyst of the kidney in children: a retrospective study of 10 cases].
AB  - INTRODUCTION: The hydatid cyst disease of the kidney is rare in children, it
      ranks third among the liver and the lung. MATERIAL: We report a series of 10
      pediatric case of hydatid cyst of the kidney, managed in the department of
      surgery pediatric of Rabat, between 1990 and 2008. RESULTS: The median age was 9
      years (4-15 years). The clinical presentation was pain (7 cases) and/or abdominal
      mass (6 cases). Diagnostic accuracy has been improved since the wide use of
      ultrasonography in eight cases. In all cases, the resection of the prominent dome
      was usually sufficient. CONCLUSION: In the light of these 10 observations, the
      ultrasonography may be sufficient and the surgical conservative treatment is
      still necessary.

PMID- 20142057
TI  - [The role of introital ultrasonography in treating low urinary tract symptoms
      complicating sub-urethral tape placement].
AB  - OBJECTIVE: To assess the role of the introital ultrasound in the evaluation of
      patients with low urinary tract symptoms after sling placement. MATERIAL AND
      METHOD: From 2000 till 2007, a total of 31 patients underwent sub-urethral tape
      placement for a stress urinary incontinence and developed thereafter a low
      urinary tract symptoms. The urological evaluation consisted of a detailed medical
      history, a urogynecologic examination, a complete urodynamic exam, a measurement
      of the postvoiding residue and a introital ultrasound. All patients filled the
      mesure du handicap urinaire (MHU) questionnaire. These patients had a
      transvaginal tape lysis under local anesthesia. We correlated the ultrasound
      findings with postoperative clinical success and failure. RESULTS: Thirty-one
      patients with low urinary tract symptoms secondary to sling placement underwent a
      tape lysis. Median age was 63.1+/-10.9 years, the median time between the anti
      incontinence surgery and the tape lysis was 21.5+/-16.2 months. Seven patients
      had only obstructive symptoms, 15 patients had obstructive and bladder
      overactivity symptoms and nine patients had bladder overactivity symptoms.
      Introital ultrasound revealed an abnormality of the tape in 26 patients. Ten
      patients had a position abnormality of the tape, five patients had urethral
      angulation abnormality and 11 patients had the previous two abnormalities. After
      tape lysis, the obstructive symptoms disappeared in 19 out of 22 patients (86%),
      the bladder overactivity symptoms disappeared in 16 out of 24 patients (66%). In
      case of introital ultrasound abnormalities, the tape lysis was efficient in 23
      out of 26 patients (89%), while in the absence of ultrasound abnormalities (five
      patients), the tape lysis was not useful in treating LUTS in all patients.
      CONCLUSION: Ultrasonography is a useful tool in investigating postoperative low
      urinary tract symptoms and in the selection of patients who will benefit from
      tape lysis.

PMID- 20142058
TI  - [PSA and spironolactone].
AB  - The spironolactone is a diuretic of potassium savings. It is also used in the
      treatment of the hirsutism for its antiandrogenic action. Its use and its effects
      on the patients affected by a prostate cancer are less known. We report the case
      of a 72-year-old man having a cancer of prostate which normalized its PSA after
      institution of a treatment by spironolactone for ascites. This patient had a
      biological recurrence of a prostate cancer, arisen 7 years later after a
      treatment by hormonal radiotherapy. Nine months after the implementation of the
      treatment by spironolactone, there were no clinical and biological signs of
      disease progress.

PMID- 20142059
TI  - [Urethral diverticulum with stone complicating epispadias repair].
AB  - Diverticula of the male urethra are rare clinical entities. Congenital and
      acquired have similar modes of presentation. No case of urethral diverticulum,
      containing stone, complicating epispadias repair have been reported. We report
      the case of 8-year-old boy with an urethral diverticulum, containing stone,
      complicating epispadias repair. Diverticulectomy with removal of the stone by
      urethroplasty was performed. Through this observation and review of the
      literature, authors describe pathological and management finding of urethral
      diverticula.

PMID- 20142060
TI  - Hip fractures.

PMID- 20142061
TI  - The basis for improving and reforming long-term care. Part 4: identifying
      meaningful improvement approaches (segment 1).
AB  - While many aspects of nursing home care have improved over time, numerous issues
      persist. Presently, a potpourri of approaches and a push to "fix" the problem
      have overshadowed efforts to correctly define the issues and identify their
      diverse causes. Together, the two segments of this fourth and final article
      (divided between this month's issue and the next one) in the series identify
      strategies that should tie reform efforts together. This Segment 1 of Article 4
      discusses the need to judge initiatives and proposals by how well they support
      and/or promote critical elements such as the care delivery process and clinical
      problem solving and decision making activities. It also covers the need to
      critically scrutinize and modify the conventional wisdom and to suppress
      "political correctness" thatcontinues to inhibit vital critical inquiry and
      dialogue that are needed to define issues correctly and make further progress.
      Ultimately, relatively uncomplicated and inexpensive strategies have the
      potential to bring dramatic progress. But there needs to be more willingness to
      rethink the issues and reconsider current approaches.

PMID- 20142062
TI  - Digital photography in long-term care.

PMID- 20142063
TI  - Contractures in nursing home residents.
AB  - Contractures represent a common but preventable source of excess disability among
      nursing home residents. They result in many negative consequences such as pain,
      increased fall risk and decreased functional ability. Studies of prevalence vary
      in the definition of contracture and thus the exact enumeration, but consistently
      report the commonality in the nursing home setting. In this population, the
      clinician should focus on tertiary prevention and/or treatment. Methods such as
      those consistent with restorative care nursing have shown improvement in function
      and are a reasonable recommendation as a preventive measure for contractures.
      Assessment, prevention, and treatment approaches are discussed.

PMID- 20142064
TI  - Hip fractures among elderly women: longitudinal comparison of physiological
      function changes and health care utilization.
AB  - OBJECTIVE: To compare physiological and functional impairments and their impact
      on health care use patterns among disabled older women with and without hip
      fracture. METHODS: Data from the 3-year longitudinal Women's Health and Aging
      Study I (WHAS-I) and Medicare Current Beneficiaries Survey (MCBS) were used for
      this comparison study. Outcome variables include physiological measures (eg, hip
      and knee strength, functional reach), functional impairments (ADLs, IADLs), and
      health care use (physician visits). Generalized Estimation Equation (GEE) models
      were used to examine the differences between groups on physiological and
      functional change and health service use over time. RESULTS: Three-year crude
      mortality rates were significantly higher in the hip fracture group (25%) than in
      the comparison group (18%); however, statistical significance did not persist
      after adjusting for age, race, education, living arrangement, depression, and
      comorbidity (RR = 1.5; P = .17). All physiological and functional measures
      deteriorated over time, regardless of presence or absence of hip fractures. After
      adjusting for covariates, the fracture group was significantly worse in knee
      strength (beta = -0.91; P = .01), usual walking speed (beta = -0.04; P = .01) and
      rapid walking speed (beta = -0.05; P = .02), and worse IADL function (beta =
      0.26; P = .002) than the non-hip fracture group. The rate of additional
      impairment for both hip fracture group and non-hip fracture group was 0.013 IADL
      units per month (P = .001). However, there were no significant differences in
      health care use between the groups. CONCLUSION: In spite of worse physiological
      and IADL impairments, once the women recovered from hip fracture surgery, they
      did not necessarily use more health care resources than non-hip fracture
      patients. To prevent functional deterioration, interventions need to focus on
      knee strength and mobility training.

PMID- 20142066
TI  - All-cause mortality rates of hip fractures treated in the VHA: do they differ
      from Medicare facilities?
AB  - PURPOSE: To estimate the 1-year all-cause mortality rates for hip fracture (HFx)
      patients hospitalized at Veterans Health Administration (VHA) facilities and
      compare with previous published mortality rates for veterans treated in Medicare
      facilities. METHODS: In total, 7 years of VHA discharge data on HFxs for 12,539
      patients age 65 and older were combined with national death registry data. We
      performed a 1-year survival analysis using the Cox proportional hazard method.
      RESULTS: The adjusted rates for veterans treated in the VHA (30 days=9.3%, 90
      days=17.5%, 180 days=23.3%, 365 days=29.8%) were similar to veterans treated in
      Medicare facilities (30 days=8.9%, 90 days=15.6%, 180 days=21.8%, 365
      days=29.9%). For veterans treated for a HFx in Medicare facilities, the average
      length of stay was 7 days and 49% were discharged to a nursing home. Veterans
      treated in the VHA had an average length of stay of 14 days and only 35% were
      discharged to a nursing home. CONCLUSIONS: Our study suggests no difference in
      HFx-adjusted mortality rates between the VHA and Medicare facilities. Given the
      institutional factor differences between Medicare and the VHA, future study and
      comparison of health outcomes for nursing home HFx patients and related costs
      between these two health care programs may contribute to the on-going health care
      reform debate.

PMID- 20142065
TI  - Adherence to hip protectors and implications for U.S. long-term care settings.
AB  - OBJECTIVES: Determine nursing home characteristics related to adherence to use of
      a hip protector (HP) to prevent fracture; also describe adherence and related
      resident characteristics. DESIGN: A multicenter, randomized controlled trial of a
      HP in which adherence to wearing the HP was monitored by research staff 3 times a
      week for up to 21 months; data were collected by interviews and chart review.
      SETTING: Thirty-five nursing homes in Boston, St. Louis, and Baltimore.
      PARTICIPANTS: A total of 797 eligible residents, 633 (79%) of whom passed the run
      in period, 397 (63%) of whom remained in the study until the end of follow-up.
      INTERVENTION: Residents wore a single HP on their right or left side.
      MEASUREMENTS: In addition to regular monitoring of adherence, data were collected
      regarding facility characteristics, staffing, policies and procedures, perception
      of HPs and related experience, and research staff ratings of environmental and
      overall quality; and also resident demographic characteristics, and function,
      health, and psychosocial status. RESULTS: Facility characteristics related to
      more adherence were not being chain-affiliated; less Medicaid case-mix; fewer
      residents wearing HPs; more paraprofessional staff training; more rotating
      workers; and having administrators who were less involved in meetings.
      CONCLUSION: Efforts to increase adherence to the use of HPs should focus on
      facilities with more Medicaid case-mix to reduce disparities in care, and those
      that have less of a culture of training. Staff may need support to increase
      adherence, and when adherence cannot be maintained, HP use should be targeted to
      those who remain adherent.

PMID- 20142067
TI  - Antipsychotic use and the risk of hip fracture among older adults afflicted with
      dementia.
AB  - OBJECTIVE: To quantify the association between use of antipsychotic (AP)
      medications and the risk of hip fracture among older adults residing in a nursing
      home (NH) and afflicted with dementia. DESIGN: Nested case-control study.
      SETTING: NHs in California, Florida, Illinois, New York, and Ohio in 2001-2002
      (N=586). PARTICIPANTS: The source population consisted of long-stay Medicaid
      eligible residents living in NHs with at least 20 beds, who were 65 years of age
      or older and had a diagnosis of dementia but were not receiving hospice care,
      were not comatose, bedfast, paralyzed, or in a wheelchair, and had no record of a
      previous hip fracture (N=69,027). There were 764 cases of hip fracture
      identified; up to 5 controls, matched to cases on NH and quarter of Minimum Data
      Set (MDS) assessment, were randomly selected from the source population (N=3582).
      MEASUREMENTS: Cases of hip fracture were identified and medication use was
      ascertained from Medicaid claims data. Resident-level characteristics, including
      dementia severity, were obtained from resident MDS assessments. RESULTS: Current
      use of APs conveyed a small increased risk of hip fracture (adjusted odds
      ratio=1.26; 95% confidence interval: 1.05 -1.52). When analyzed separately, users
      of conventional antipsychotics had a slightly higher risk of hip fracture than
      residents on atypical agents. Long-term use of APs conferred a greater risk of
      hip fracture than short-term use. CONCLUSION: APs appear to increase the risk of
      hip fracture among older adults with dementia residing in an NH. Hip fractures
      may be a contributory mechanism to the increased risk mortality observed among AP
      users.

PMID- 20142068
TI  - Testing for vitamin D deficiency in veterans-is there a seasonal bias?
AB  - OBJECTIVE: The present study was undertaken to determine if a seasonal bias was
      present for vitamin D testing among Northeast Tennessee veterans, in whom vitamin
      D deficiency is common. DESIGN: Medical chart review. SETTING: VA Medical Center.
      PARTICIPANTS: Participants were 9447 patients with initial 25(OH) vitamin D
      levels obtained over a 3-year period. MEASUREMENT: Serum 25-hydroxyvitamin D
      (25[OH]D) level, date of testing, patient background factors. RESULTS: Vitamin D
      testing occurred more frequently in September, October, November, and December,
      whereas the lowest levels of 25(OH) vitamin D levels were found in January,
      February, and March. Similar results were observed in quarterly data with the
      greatest number of tests noted in the last quarter of the year, yet the lowest
      25(OH) vitamin D levels were noted in the first quarter. The average monthly
      25(OH) vitamin D levels were below 30 ng/mL throughout the year in the study
      population, consistent with highly prevalent vitamin D deficiency. CONCLUSION:
      Clinicians may have a seasonal bias, favoring testing for vitamin D status in the
      latter part of the year even though the lowest vitamin D levels are observed in
      the first part of the year. Although an argument could be made to check for peak
      25(OH) vitamin D levels in September and trough levels in March, the seasonal
      contribution to vitamin D deficiency is overshadowed by ongoing vitamin D
      deficiency throughout the year. Thus, it may be prudent to test for vitamin D
      deficiency in patients presenting with fatigue, myalgias, and arthralgias
      regardless of the season of presentation.

PMID- 20142069
TI  - Examining heterogeneity of functional recovery among older adults with hip
      fractures.
AB  - OBJECTIVE: To examine heterogeneity in 1-year functional recovery following
      postacute rehabilitation among older adults with hip fracture. METHODS: Two
      hundred twenty-five community-dwelling older adults with hip fracture who
      received postacute rehabilitation in 5 rehabilitation facilities in Baltimore,
      Maryland, were recruited during postacute rehabilitation (baseline) and follow-up
      at 2, 6, and 12 months following postacute rehabilitation discharge. Functional
      recovery was measured by the activities of daily living (ADL) and instrumental
      activities of daily living (IADL) scores. A mixed-effect model was used to
      examine factors associated with postacute rehabilitation functional recovery;
      fixed and random effects estimates from the models were used to demonstrate
      heterogeneity in functional recovery. RESULTS: Results indicated that there was
      an overall trend in both ADL and IADL functional improvement at 2 months
      following postacute rehabilitation, with continued improvement to 6 months, after
      which functional recovery slowed down and remained constant through the year.
      Individuals whose functional recovery did not conform to these patterns were
      identified and their functional recovery that deviated substantially from the
      group mean was demonstrated. CONCLUSIONS: Functional recovery patterns in elderly
      hip fracture patients are heterogeneous. To foster functional independence,
      health care professionals should consider individual recovery trajectories using
      a modeling approach appropriate for longitudinal or repeated measurement data
      such as a linear mixed-effects model when designing individualized rehabilitation
      and postacute rehabilitation care plans.

PMID- 20142071
TI  - Dream from our President: Barack Obama and evidence-based medicine.

PMID- 20142070
TI  - Determinants of living situation in a population of community-dwelling and
      assisted living-dwelling elders.
AB  - OBJECTIVE: To determine what variables separate community-dwelling elders from
      assisted living-dwelling elders. DESIGN: Cross-sectional. SETTING: Community and
      assisted living facilities in Connecticut. PARTICIPANTS: 114 individuals (77
      community dwelling, 37 assisted living). ASSESSMENTS: Nutritional survey, 6
      minute walk, Mini-Mental Status Exam (MMSE), Center of Epidemiologic Studies
      (CES)-Depression Scale, 25-OH vitamin D. RESULTS: At baseline, assisted living
      dwelling elders appeared to have lower serum 25-OH vitamin D levels, lower MMSE
      scores, higher CES-depression scale scores, and walked shorter distances in the 6
      minute walk. Serum 25-OH vitamin D levels and 6-minute walk were significantly
      different between the 2 groups using logistic regression analysis. As serum 25-OH
      vitamin D levels increased, the probability of an elder living in an assisted
      living facility decreased, and as distance walked during the 6-minute walk
      increased, the probability of an elder living in an assisted living facility
      decreased. CONCLUSIONS: Elders living in assisted living facilities had
      significantly lower 25-OH vitamin D levels and walked shorter distances during
      the 6-minute walk. These variables can be used to predict the probability of an
      elder living in an assisted living facility. The lack of effect of nutrition
      suggests that the role of vitamin D in this setting is in physical function.

PMID- 20142072
TI  - Volumetric analysis of thoracic and lumbar vertebral bodies.
AB  - BACKGROUND CONTEXT: During the last decade, vertebral augmentation techniques
      with cement (kyphoplasty and vertebroplasty) have revealed that 75% to 100% of
      individuals with osteoporotic vertebral compression fractures have good to
      moderate pain relief postoperatively, as well as adequate restoration of the
      vertebral body height. The volume of cement injected into a vertebra varied in
      different reports. To our knowledge, there are no studies that report on the
      physiological distribution of thoracic and lumbar vertebrae body volumes.
      PURPOSE: The purpose of this study was to quantitatively evaluate thoracic and
      lumbar vertebral body volumes. STUDY DESIGN/SETTING: Forty computed tomography
      (CT) scans of the thoracic and lumbar spines were used to measure a volume of
      each vertebral body. METHODS: Forty CT scans with standard 2.5-mm bone window
      cuts of the thoracic and lumbar vertebrae (20 men and 20 women) were analyzed to
      measure the volumetric capacity of vertebral bodies using a BrainLAB Software
      (iPlan RT image 4.0) program. The software was tested for validity and
      reliability in two pilot studies. Mean and standard deviations for each vertebral
      body volume were calculated and recorded. The vertebral body working distance and
      the so-called "safe zone" were also measured to determine a size of a balloon to
      be used in kyphoplasty. RESULTS: Vertebral body volume increased gradually from
      T1 to L4 with the exception of L5, which measured to be smaller than L4. The mean
      thoracic vertebrae volume was 15.0 cm(3) (ranged in the absolute values from 5.2
      to 39.5 cm(3)), and the mean lumbar vertebrae volume was 35 cm(3) (ranged in the
      absolute values from 19.7 to 61.5 cm(3)). Men had larger volume vertebral bodies
      only in the lumbar spine compared with women. The average vertebral body working
      distances from T1 to T4 was 23.4+/-2.7 mm, from T5 to T9 was 30.3+/-3.6 mm, and
      from T10 to L5 was 35.5+/-3.9 mm. CONCLUSIONS: Knowing the physiological
      variability of vertebral body volumes may help prevent complications as a result
      of underaugmentation or overaugmentation with excessive amount of cement during
      kyphoplasty or vertebroplasty in osteoporotic compression fractures. We recommend
      using 10 mm balloons from T1 to T4, 15 mm balloons from T5 to T9, and 20 mm
      balloons from T10 to L5 for kyphoplasty.

PMID- 20142073
TI  - Effect of bupivacaine on chondrocyte viability.

PMID- 20142074
TI  - Aggressive end plate decortication as a cause of osteolysis after rhBMP-2 use in
      cervical spine interbody fusion.

PMID- 20142076
TI  - Medical value vs cost and risk: redux.

PMID- 20142077
TI  - What would happen if...?

PMID- 20142078
TI  - Radiology and epigenetics.

PMID- 20142079
TI  - Tracking radiation exposure from diagnostic imaging devices at the NIH.

PMID- 20142080
TI  - Dartmouth interrupted.

PMID- 20142081
TI  - Looking ahead: 2010 OIG Work Plan.

PMID- 20142082
TI  - ACR Appropriateness Criteria on Crohn's disease.
AB  - In the past decade, new therapeutic agents have been developed that permit
      gastroenterologists to treat virtually all forms of Crohn's disease. The success
      of these treatments depends on an accurate diagnosis of the nature and extent of
      disease. Fortunately, radiologists now possess a powerful arsenal of imaging
      techniques to guide the choice of therapy. This article discusses the usefulness
      of both traditional and newer imaging techniques in the management of Crohn's
      disease and its various clinical presentations.

PMID- 20142083
TI  - The 2009 ACR Forum: health care payment models.
AB  - The 2009 ACR Forum addressed health care payment models, the strengths and
      weaknesses of different models under consideration, their implications for
      radiology, and the role radiologists should play in the debate.

PMID- 20142084
TI  - The ACR guideline on communication: to be or not to be, that is the question.
AB  - The ACR has published more than 160 guidelines to assist radiologists in quality
      practice. One of the most controversial guidelines is on communication, first
      adopted more than a decade ago. This guideline is coming up for reconsideration
      and perhaps revision by the ACR Council at the ACR AMCLC in Washington, DC, in
      May 2010. In preparation for that reconsideration, the authors reviewed the
      guideline and its impact since last modified 5 years ago. The review shows that
      communication is still an important issue in radiology and that the guideline has
      played an overall beneficial role.

PMID- 20142085
TI  - Off-label use of medical devices in radiology: regulatory standards and recent
      developments.
AB  - The US Food and Drug Administration (FDA) enjoys a broad legal mandate to ensure
      that medical products are safe and effective for their intended uses, authority
      that extends to the medical devices that make modern radiology possible. Under
      FDA's regulatory framework, medical devices are cleared or approved for specific
      indications for use that are described in the labeling provided with the devices.
      This article outlines this framework as well as the regulatory and legal
      implications of using medical devices in a manner inconsistent with their FDA
      cleared or FDA-approved labeling.

PMID- 20142086
TI  - Quantifying radiation safety and quality in medical imaging, part 4: the medical
      imaging agent scorecard.
AB  - The Institute of Medicine has determined that adverse drug events (ADEs) are the
      number one cause of medical errors in the United States and that additional
      efforts are required to improve patient safety. Medical imaging plays an
      important role in ADEs, most commonly related to the administration of imaging
      contrast agents. For medical imaging providers to assume a proactive role in
      patient safety, the creation of objective, data-driven quality metrics is
      advocated, which analyze all steps in the drug delivery chain, including
      procurement, prescription, dispersal, administration, monitoring, and management.
      These metrics would lead to the creation of a quality scorecard, developed to
      create objective accountability measures for all actors involved in this chain of
      events, including pharmacists, radiologists, clinicians, physicists,
      technologists, administrators, nurses, vendors, and patients. The ultimate goal
      of such an endeavor is to improve patient safety through the reduction of ADEs
      and the creation and refinement of data-driven best-practice guidelines.

PMID- 20142087
TI  - Evaluation of coronary CTA Appropriateness Criteria in an academic medical
      center.
AB  - BACKGROUND: The aim of this study was to evaluate published appropriateness
      criteria for CT angiography (CTA) at the authors' academic medical center.
      METHODS: Two observers independently reviewed the medical records of 251 patients
      who had undergone dual-source coronary CTA from June 1 to December 31, 2007.
      Patients were assigned to indications from 1 of 7 tables from the American
      College of Cardiology Foundation and ACR Appropriateness Criteria. Agreement
      between the two observers was assessed using kappa statistics. Disagreements were
      resolved by consensus panel. The final numbers of appropriate, uncertain,
      inappropriate, and not classifiable indications were recorded. RESULTS:
      Indications for testing were classified as appropriate in 69 patients (27%),
      inappropriate in 42 patients (17%), and uncertain in 25 patients (10%). One
      hundred fifteen indications for coronary CTA (46%) were not classifiable.
      Analysis of interobserver variability for overall appropriateness yielded a kappa
      value of 0.31, which was considered to indicate fair agreement. CONCLUSION: The
      results of this study suggest that a significant proportion (46%) of the coronary
      CTA studies performed at the authors' institution are for indications that are
      not covered by the published appropriateness criteria. Modifications to these
      criteria could help decrease the number of studies that are not classifiable.
      Physician education could decrease the number of inappropriate studies.

PMID- 20142088
TI  - The ACR Diagnostic Radiology In-Training Examination: evolution, current status,
      and future directions.
AB  - The ACR Diagnostic Radiology In-Training Examination is administered yearly to
      radiology residents nationwide. It is primarily an educational tool for the
      assessment of radiologists-in-training and for the programs in which they reside.
      Over the past 5 years, the examination has undergone several changes, and more
      are anticipated in the near future. This review article discusses the recent
      changes to the examination, outlines the examination development process, gives
      statistics and data from the most recent test administrations, and anticipates
      issues for future examinations.

PMID- 20142089
TI  - Videoconferencing of a national program for residents on evidence-based practice:
      early performance evaluation.
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of the medium of
      videoconferencing for the delivery of a course for radiology residents in
      practice-based learning (PBL), including evidence-based practice, at centers
      geographically separated from the principal teaching site. MATERIALS AND METHODS:
      Twenty-one participants (second-year radiology residents) at 8 centers in a
      radiology training program were included. The course in PBL was delivered over 16
      weekly 1-hour sessions. There were 8 local education site coordinators (staff
      radiologists), who had completed an intensive 1-day course at the principal
      teaching site. The host site was linked to the participant sites using
      videoconferencing technology. Course evaluation included 1) a 5-point Likert-type
      scale and an open-ended evaluation questionnaire midway through the course (week
      8) and a summation questionnaire after its completion (week 16) and 2) a
      consultation forum held during the penultimate session. The data responses to the
      questionnaires were entered in a spreadsheet, and the data were analyzed.
      Qualitative data were manually coded and analyzed for common themes. Descriptive
      statistical analyses were performed. RESULTS: Eighty-five percent of evaluation
      questionnaires and 53% of summation questionnaires were returned. The overall
      satisfaction of the participants with course content was high, with median rating
      of 4 on the 5-point scale. All participants agreed that videoconferencing as a
      medium did not hinder adequate discussion among centers and worked well as an
      interactive teaching method (median, 4). Local coordinators were satisfied with
      local technical support and training (median, 4), and overall, the module was
      rated highly, with ratings of 4 from both residents and local coordinators.
      Seventy-one percent of residents and 86% of local coordinators reported that they
      would have been unable to participate in the course without videoconferencing.
      All participants completed the course requirements satisfactorily. The overall
      rating of audio quality was good (median, 4), but there was dissatisfaction with
      the quality of the visual aids used. Comments reflected a desire for a shorter,
      more condensed course; improvement of the quality of visual aids; and more
      emphasis on research appraisal. CONCLUSION: Although videoconferencing is a
      valuable educational tool and works well as a didactic teaching method,
      challenges with interactive discussion between centers require further
      exploration. This technology allows the inclusion of trainers and trainees who
      may otherwise be unable to participate. In multicenter programs, this can be
      fundamental to the feasibility and sustainability of educational programs in
      newer competencies, for which a lack of a critical mass of educators and students
      can be problematic for individual centers.

PMID- 20142090
TI  - Introducing "Quality Matters".

PMID- 20142091
TI  - Communicating critical results in radiology.

PMID- 20142092
TI  - Health care reform through meaningful use of health care IT: implications for
      radiologists.

PMID- 20142093
TI  - Advances in computed radiography: dual-side readout.

PMID- 20142095
TI  - Re: "CMS's landmark decision on CT colonography": misguided and short-sighted:
      pay me now or pay me later.

PMID- 20142096
TI  - Re: "data presentation bias: a source of potential error in radiology scientific
      publications".

PMID- 20142097
TI  - Treating obesity? It's in the bag!
AB  - BRS-3 is an orphan G protein coupled receptor highly expressed in the brain.
      Pharmacological studies in this issue (Guan et al., 2010) further support a role
      for this receptor in energy homeostasis and show that the BRS-3 agonist Bag-1
      effectively causes weight loss by decreasing food intake and increasing metabolic
      rate.

PMID- 20142098
TI  - Blood pressure AsSAuLTed by the circadian clock.
AB  - While Cry proteins are necessary for circadian rhythmicity, they now appear to
      play a seminal role in blood pressure regulation. In a recent issue of Nature
      Medicine, Doi et al., 2009 show how the circadian clock may use Cry proteins to
      protect from salt-sensitive hypertension.

PMID- 20142099
TI  - Fyn-dependent regulation of energy expenditure and body weight is mediated by
      tyrosine phosphorylation of LKB1.
AB  - Fyn null mice display reduced adiposity associated with increased fatty acid
      oxidation, energy expenditure, and activation of the AMP-dependent protein kinase
      (AMPK) in skeletal muscle and adipose tissue. The acute pharmacological
      inhibition of Fyn kinase activity with SU6656 in wild-type mice reproduces these
      metabolic effects and induced a specific reduction in fat mass with no change in
      lean mass. LKB1, the main upstream AMPK kinase (AMPKK) in peripheral tissues, was
      redistributed from the nucleus into the cytoplasm of cells treated with SU6656
      and in cells expressing a kinase-deficient, but not a constitutively kinase
      active, Fyn mutant. Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine
      261 and 365 residues, and mutations of these sites resulted in LKB1 export into
      the cytoplasm and increased AMPK phosphorylation. These data demonstrate a
      crosstalk between Fyn tyrosine kinase and the AMPK energy-sensing pathway,
      through Fyn-dependent regulation of the AMPK upstream activator LKB1.

PMID- 20142100
TI  - A macrophage sterol-responsive network linked to atherogenesis.
AB  - Cholesteryl ester accumulation by macrophages is a critical early event in
      atherogenesis. To test the hypothesis that sterol loading promotes foam cell
      formation and vascular disease by perturbing a network of interacting proteins,
      we used a global approach to identify proteins that are differentially expressed
      when macrophages are loaded with cholesterol in vivo. Our analysis revealed a
      sterol-responsive network that is highly enriched in proteins with known physical
      interactions, established roles in vesicular transport, and demonstrated
      atherosclerotic phenotypes in mice. Pharmacologic intervention with a statin or
      rosiglitazone and use of mice deficient in LDL receptor or apolipoprotein E
      implicated the network in atherosclerosis. Biochemical fractionation revealed
      that most of the sterol-responsive proteins resided in microvesicles, providing a
      physical basis for the network's functional and biochemical properties. These
      observations identify a highly integrated network of proteins whose expression is
      influenced by environmental, genetic, and pharmacological factors implicated in
      atherogenesis.

PMID- 20142101
TI  - FoxO-mediated defense against oxidative stress in osteoblasts is indispensable
      for skeletal homeostasis in mice.
AB  - Aging increases oxidative stress and osteoblast apoptosis and decreases bone
      mass, whereas forkhead box O (FoxO) transcription factors defend against
      oxidative stress by activating genes involved in free radical scavenging and
      apoptosis. Conditional deletion of FoxO1, FoxO3, and FoxO4 in 3-month-old mice
      resulted in an increase in oxidative stress in bone and osteoblast apoptosis and
      a decrease in the number of osteoblasts, the rate of bone formation, and bone
      mass at cancellous and cortical sites. The effect of the deletion on osteoblast
      apoptosis was cell autonomous and resulted from oxidative stress. Conversely,
      overexpression of a FoxO3 transgene in mature osteoblasts decreased oxidative
      stress and osteoblast apoptosis and increased osteoblast number, bone formation
      rate, and vertebral bone mass. We conclude that FoxO-dependent oxidative defense
      provides a mechanism to handle the oxygen free radicals constantly generated by
      the aerobic metabolism of osteoblasts and is thereby indispensable for bone mass
      homeostasis.

PMID- 20142105
TI  - Back to the big tent.

PMID- 20142102
TI  - FoxO1 is a positive regulator of bone formation by favoring protein synthesis and
      resistance to oxidative stress in osteoblasts.
AB  - Osteoporosis, a disease of low bone mass, is associated with decreased osteoblast
      numbers and increased levels of oxidative stress within osteoblasts. Since
      transcription factors of the FoxO family confer stress resistance, we
      investigated their potential impact on skeletal integrity. Here we employ cell
      specific deletion and molecular analyses to show that, among the three FoxO
      proteins, only FoxO1 is required for proliferation and redox balance in
      osteoblasts and thereby controls bone formation. FoxO1 regulation of osteoblast
      proliferation occurs through its interaction with ATF4, a transcription factor
      regulating amino acid import, as well as through its regulation of a stress
      dependent pathway influencing p53 signaling. Accordingly, decreasing oxidative
      stress levels or increasing protein intake normalizes bone formation and bone
      mass in mice lacking FoxO1 specifically in osteoblasts. These results identify
      FoxO1 as a crucial regulator of osteoblast physiology and provide a direct
      mechanistic link between oxidative stress and the regulation of bone remodeling.

PMID- 20142103
TI  - Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell
      response and new bone formation.
AB  - Parathyroid hormone (PTH) suppresses Dickkopf 1 (Dkk1) expression in osteoblasts.
      To determine whether this suppression is essential for PTH-mediated Wnt signaling
      and bone formation, we examined mice that overexpress Dkk1 in osteoblasts (Dkk1
      mice). Dkk1 mice were osteopenic due to abnormal osteoblast and osteoclast
      activity. When fed a low-calcium diet, and in two other models of
      hyperparathyroidism, these mice failed to develop the peritrabecular stromal cell
      response ("osteitis fibrosis") and new bone formation seen in wild-type mice.
      Despite these effects of Dkk1 overexpression, PTH still activated Wnt signaling
      in Dkk1 mice and in osteoblastic cells cultured from these mice. In cultured
      MC3T3E1 preosteoblastic cells, PTH dramatically suppressed Dkk1 expression,
      induced PKA-mediated phosphorylation of beta-catenin, and significantly enhanced
      Lef1 expression. Our findings indicate that the full actions of PTH require
      intact Wnt signaling but that PTH can activate the Wnt pathway despite
      overexpression of Dkk1.

PMID- 20142107
TI  - Improvement of the microstructure and mechanical properties of bioceramic
      scaffolds using electrohydrodynamic spraying with template modification.
AB  - Porous scaffolds play a key role in tissue engineering (TE) approaches and new
      processing methods and materials are constantly being developed to cater for the
      wide range of specifications and requirements. Electrospraying is a relatively
      new processing method used for producing open-pore scaffolds. In this work, the
      electrospraying technique was manipulated to make the process more efficient, and
      the effect of spraying time on the pore size and strut thickness of zirconia
      scaffolds was explored. Scaffolds of adequate pore size and interconnectivity,
      with an average compressive strength of approximately 7.5 MPa, by electrospraying
      for only 10 min are reported. The effect of modifying the sacrificial template on
      the microstructure and mechanical properties of the sintered scaffolds was also
      investigated. A combination of template surface hydroxylation and improved
      conductivity produced a thicker ceramic coating, leading to enhanced mechanical
      properties.

PMID- 20142108
TI  - Estimation of bone permeability considering the morphology of lacuno-canalicular
      porosity.
AB  - Load-induced interstitial fluid flow in lacuno-canalicular porosity is believed
      to play an important role in cellular activities regulating adaptive bone
      remodeling. To investigate interstitial fluid behavior based on poroelasticity,
      it is important to determine the anisotropic permeability tensor reflecting the
      morphological features of the lacuno-canalicular porosity as fluid channels. In
      this study, we presented an estimation method of trabecular permeability by
      describing the analytical relationship between the volume orientation (VO) fabric
      tensor, which represents the canalicular orientation, and the permeability
      tensor. The relationship showed that the trabecular permeability tensor is
      proportional to the product of the volume fraction of the interstitial fluid and
      the VO fabric tensor of the canaliculi. We applied the proposed method to a two
      dimensional fluorescent image of a trabecular cross section to quantify the
      canalicular anisotropy and the trabecular permeability tensor. The results
      indicated that the canaliculi are predominantly oriented in the radial direction
      of the trabecula, and the permeability depends strongly on the canalicular
      morphology.

PMID- 20142109
TI  - Mechanical evaluation of porous titanium (Ti6Al4V) structures with electron beam
      melting (EBM).
AB  - Patient specific porous implants for the reconstruction of craniofacial defects
      have gained importance due to their better performance over their generic
      counterparts. The recent introduction of electron beam melting (EBM) for the
      processing of titanium has led to a one step fabrication of porous custom
      titanium implants with controlled porosity to meet the requirements of the
      anatomy and functions at the region of implantation. This paper discusses an
      image based micro-structural analysis and the mechanical characterization of
      porous Ti6Al4V structures fabricated using the EBM rapid manufacturing process.
      SEM studies have indicated the complete melting of the powder material with no
      evidence of poor inter-layer bonding. Micro-CT scan analysis of the samples
      indicate well formed titanium struts and fully interconnected pores with
      porosities varying from 49.75%-70.32%. Compression tests of the samples showed
      effective stiffness values ranging from 0.57(+/-0.05)-2.92(+/-0.17)GPa and
      compressive strength values of 7.28(+/-0.93)-163.02(+/-11.98)MPa. For nearly the
      same porosity values of 49.75% and 50.75%, with a variation in only the strut
      thickness in the sample sets, the compressive stiffness and strength decreased
      significantly from 2.92 GPa to 0.57 GPa (80.5% reduction) and 163.02 MPa to 7.28
      MPa (93.54 % reduction) respectively. The grain density of the fabricated Ti6Al4V
      structures was found to be 4.423 g/cm(3) equivalent to that of dense Ti6Al4V
      parts fabricated using conventional methods. In conclusion, from a mechanical
      strength viewpoint, we have found that the porous structures produced by the
      electron beam melting process present a promising rapid manufacturing process for
      the direct fabrication of customized titanium implants for enabling personalized
      medicine.

PMID- 20142110
TI  - Influence of viscoelasticity of protein on the toughness of bone.
AB  - Bone is an ultrafine composite of protein (collagen) and mineral
      (hydroxyapatite). An analysis to determine the influence of the viscoelasticity
      of protein on the toughness of bone at the ultrafine scale is conducted by
      developing a discrete lattice model appropriate for the ultrafine scale called
      the incremental continuous damage random fuse model (ICDRFM). Collagen
      viscoelasticity at ultrafine scale is shown to contribute significantly to the
      toughness of bone. The results obtained are important in the design of biomimetic
      ultratough artificial composites.

PMID- 20142111
TI  - Finite element simulation of cell-substrate decohesion by laser-induced stress
      waves.
AB  - Fundamental to the development and application of biomedical devices is an
      understanding of the adhesion of cells to substrates. There are many experimental
      techniques and papers dedicated to the study of cell adhesion. This work aims to
      elucidate on the cell detachment mechanism in a recently reported cell adhesion
      measurement experiment by laser-induced stress wave technique. In the experiment
      the absorption of an Nd:YAG laser pulse generates a stress wave of nanoseconds
      duration that interacts with and detaches the cell adhered to a Si substrate. Due
      to the ultra-short timescale involved in the experiment, details of the
      detachment process were not readily observable. In this work, dynamic finite
      element method is used to simulate the cell-substrate decohesion process under
      the laser-induced stress wave loading. The results show that the combined effect
      of nanosecond stress wave pulse and the specific cell geometry results in a
      complex stress-strain state along the cell-substrate interface. The principal
      failure mechanism is large interfacial strains realized from the cell's tendency
      to spread and elongate on the substrate as a result of substrate acceleration.
      The cells behave like a soft elastic solid during the detachment process due to
      the large difference between their characteristic response time and the ultra
      short duration of the applied stress wave. Evolution of the cell geometry from
      hydrophobic to hydrophilic contact results in the same detachment process.

PMID- 20142112
TI  - The consolidation behavior of silk hydrogels.
AB  - Hydrogels have mechanical properties and structural features that are similar to
      load-bearing soft tissues including intervertebral disc and articular cartilage,
      and can be implanted for tissue restoration or for local release of therapeutic
      factors. To help predict their performance, mechanical characterization and
      mathematical modeling are the available methods for use in tissue engineering and
      drug delivery settings. In this study, confined compression creep tests were
      performed on silk hydrogels, over a range of concentrations, to examine the
      phenomenological behavior of the gels under a physiological loading scenario.
      Based on the observed behavior, we show that the time-dependent response can be
      explained by a consolidation mechanism, and modeled using Biot's poroelasticity
      theory. Two observations are in strong support of this modeling framework,
      namely, the excellent numerical agreement between increasing load step creep data
      and the linear Terzaghi theory, and the similar values obtained from numerical
      simulations and direct measurements of the permeability coefficient. The higher
      concentration gels (8% and 12% w/v) clearly show a strain-stiffening response to
      creep loading with increasing loads, while the lower concentration gel (4% w/v)
      does not. A nonlinear elastic constitutive formulation is employed to account for
      the stiffening. Furthermore, an empirical formulation is used to represent the
      deformation-dependent permeability.

PMID- 20142113
TI  - Elderly patient with coronary heart disease: time for appraisal.

PMID- 20142114
TI  - Predictors of B-type natriuretic peptide and left atrial volume index in patients
      with preserved left ventricular systolic function: an echocardiographic
      catheterization study.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) and left atrial volume index (LAVi)
      are used as surrogate measures for global myocardial function and are recommended
      for the diagnosis of heart failure with normal ejection fraction. Little is
      known, however, about predictors in patients with preserved systolic function.
      AIMS: To identify factors that influence the relation of BNP and left atrial size
      to invasively determined left ventricular end-diastolic pressure in stable
      patients with preserved left ventricular systolic function. METHODS: Fifty-nine
      consecutive patients were included prospectively. Clinical, biological, Doppler
      echocardiographic and invasive variables were collected simultaneously. RESULTS:
      BNP was predicted independently by left ventricular ejection fraction, diastolic
      function and age (p<0.05). LAVi was predicted independently by left ventricular
      mass index and invasive left ventricular end-diastolic pressure (p<0.01). BNP
      predicted increased left ventricular end-diastolic pressure greater than 16 mmHg
      (p=0.004); the optimal cut-off value was 33 pg/mL (area under the receiver
      operating characteristic curve [AUC] 0.74 [0.6-0.84], p<0.001, sensitivity 72%,
      specificity 70%). LAVi predicted increased left ventricular end-diastolic
      pressure (p<0.001); the optimal cut-off value for LAVi was 26 mL/m(2) (AUC 0.87
      [0.75-0.94], p<0.001; sensitivity 85%, specificity 80%). Unlike BNP (p=0.1), LAVi
      performed well in patients with abnormal relaxation at mitral filling (p<0.01).
      CONCLUSION: BNP is influenced by age in stable patients with preserved systolic
      function and should be interpreted cautiously. LAVi is a powerful surrogate for
      invasively determined left ventricular end-diastolic pressure regardless of age
      and mitral filling.

PMID- 20142115
TI  - Influence of polymorphisms in candidate genes on early vascular alterations in
      obese children.
AB  - BACKGROUND: Many studies performed in adults have reported the involvement of
      genetic determinants in vascular alterations that predispose to cardiovascular
      diseases later in life. To date, no study has assessed the co-involvement of gene
      polymorphisms as cardiovascular risk factors in children. AIMS: To search for
      variants involved in early vascular alterations in obese children. METHODS: In
      232 obese children, we performed an association study between variables related
      to endothelial function or arterial mechanical properties and functional variants
      reported to predispose towards vascular alterations in adults. Candidate
      polymorphisms were selected in genes involved in the renin-angiotensin system,
      vascular endothelial cell remodelling and communication, arterial inflammation,
      adiponectin production and lipoprotein metabolism. Non-invasive arterial
      measurements were performed to evaluate the mechanical characteristics of the
      common carotid artery and the endothelial function of the brachial artery.
      RESULTS: We found no association between the polymorphisms studied, taken alone
      or in combination with the arterial variables measured. CONCLUSION: Our
      hypothesis predicting that the tested genetic variants, which are involved in
      adult cardiovascular diseases, may influence the susceptibility to early vascular
      alterations in obese children was not validated. Thus, obesity-associated
      metabolic complications appear to remain the main predictors of arterial
      alterations in obese children.

PMID- 20142116
TI  - Functional decline in elderly patients presenting with acute coronary syndromes:
      impact on midterm outcome.
AB  - BACKGROUND: Elderly patients with an acute coronary syndrome (ACS) are less
      likely to be enrolled into randomized, controlled trials or receive guideline
      recommended therapies, because of a higher burden of comorbidity, including
      functional decline. AIM: To assess the prognostic value of functional decline in
      a prospective, observational cohort of elderly ACS patients. METHODS: ACS
      patients aged > or = 70 years were enrolled. The ACS definition included ST- and
      non-ST-segment elevation myocardial infarction, and unstable angina pectoris.
      Clinical admission and laboratory data and echocardiographic variables were
      recorded. Functional decline was defined as needing assisted care in daily life.
      The study endpoint was all-cause mortality. RESULTS: Overall, 151 patients were
      enrolled (mean age 78 + or - 5 years; 52% men). Twenty-eight (19%) patients had
      functional decline. No significant difference in therapeutic management was
      observed between patients with functional decline and those living independently.
      Twenty-seven (18%) patients died during follow-up (median 447 days). Functional
      decline correlated with poor outcome (p = 0.008; hazard ratio [HR] 2.87 [1.31
      6.25]). Other prognostic markers were diabetes, Killip class > or = II, elevated
      E/Ea ratio, C-reactive protein, B-type natriuretic peptide, haemoglobin,
      glycaemia and no coronary angiography. By multivariable analysis, C-reactive
      protein >13 mg/L correlated with poor outcome (p = 0.007; HR 4.77 [1.52-14.96]).
      There was a trend towards correlation between functional decline and poor outcome
      (p = 0.051; HR = 2.77 [0.99-7.72]). CONCLUSION: Functional decline seems to
      portend poor prognosis in elderly ACS patients. Larger, community-based studies
      are needed to confirm these findings in a multivariable model.

PMID- 20142118
TI  - Thrombus aspiration for the treatment of definite stent thrombosis.
AB  - BACKGROUND: Thrombus aspiration (TA) has been associated with high rates of
      thrombotic material retrieval, which results in improved myocardial reperfusion.
      In addition, a recent study has shown that systematic TA for treatment of ST
      segment elevation myocardial infarction (STEMI) related to de novo lesions
      improves patient outcomes. AIMS: Evaluation of a single-centre experience of TA
      before percutaneous coronary intervention (PCI) for stent thrombosis (ST)
      treatment. METHODS: Between 2004 and 2006, we indexed 24 patients presenting with
      definite ST. All patients underwent TA (Export Medtronic 6F catheter) followed by
      PCI for ST treatment. Baseline clinical and angiographic characteristics, and
      complications related to the TA device were indexed. RESULTS: The median time of
      ST occurrence was 7 days. All patients except one presented with STEMI. Bare
      metal and drug-eluting ST represented 70.8% and 29.2% of cases, respectively.
      Mean stent length was 18.8 + or - 5.6mm; mean stent diameter was 2.8 + or -
      0.4mm; mean number of implanted stents was 1.58 + or - 0.7. There was no failure
      to cross the catheter and no TA device-related complications were reported. The
      numbers of patients with initial thrombolysis in myocardial infarction (TIMI)
      flow grades 0, 1 and 2 were 15 (62.5%), 3 (12.5%) and 6 (25.0%), respectively. No
      patient had TIMI flow grade 3 before TA. After TA, 16 (66.7%) patients had TIMI
      flow grade 3; final procedural success was obtained in 23 (95.8%) patients. The 1
      year death rate was 12.5%. CONCLUSIONS: In our experience, TA before PCI for ST
      treatment shows promising results, providing high rates of immediate reperfusion
      and final angiographic success, and low death rates, compared with the
      literature.

PMID- 20142117
TI  - Efficacy of simvastatin or ezetimibe on tissue factor, von Willebrand's factor
      and C-reactive protein in patients with hypercholesterolaemia.
AB  - BACKGROUND: Statins have favourable effects on lipid profiles, decrease total
      mortality and have many pleiotropic effects. AIMS: To determine and compare the
      pleiotropic effects of simvastatin and ezetimibe in dyslipidaemic patients.
      METHODS: Forty-four patients (20 postmenopausal women) with low-density
      lipoprotein cholesterol >130 mg/dL (or >100mg/dL in patients with coronary artery
      disease or its equivalent) were treated with simvastatin 10mg daily (n = 21) or
      ezetimibe 10mg daily (n = 23). In blood samples taken before and three months
      after treatment, we measured the concentration of total cholesterol,
      triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, apolipoprotein A, apolipoprotein B, lipoprotein(a), homocysteine,
      tissue factor, von Willebrand's factor and C-reactive protein. RESULTS: Baseline
      lipid profiles and haematological variables were similar in both groups.
      Simvastatin and ezetimibe decreased the concentrations of total cholesterol (262
      to 189 mg/dL, p < 0.001, and 268 to 220 mg/dL, p = 0.001, respectively), low
      density lipoprotein cholesterol (177 to 114 mg/dL, p < 0.001 and 196 to 146
      mg/dL, p < 0.001, respectively) and C-reactive protein (1.2 to 0.3 mg/dL, p =
      0.001 and 2.8 to 0.8 mg/dL, p = 0.005, respectively). Simvastatin also reduced
      the concentration of apolipoprotein B (125 to 93 mg/dL, p < 0.001). CONCLUSION:
      Both drugs improved lipid profiles and C-reactive protein concentration. However,
      no influence was found on tissue factor or von Willebrand's factor. Our results
      suggest that C-reactive protein lowering may occur in conjunction with low
      density-lipoprotein cholesterol lowering and not through a specific statin
      pleiotropic anti-inflammatory effect.

PMID- 20142119
TI  - Clopidogrel response: head-to-head comparison of different platelet assays to
      identify clopidogrel non responder patients after coronary stenting.
AB  - OBJECTIVES: We investigated the agreement between different platelet tests to
      identify clopidogrel non response. BACKGROUND: Biological definition of
      clopidogrel non response remains controversial. Different platelet tests have
      been linked with recurrent ischemic events and proposed for daily practice.
      METHODS: We prospectively investigated the agreement of platelet tests to isolate
      clopidogrel non response in patients receiving high 150 mg clopidogrel
      maintenance dose after coronary stenting. Clopidogrel response was assessed with
      ADP-induced aggregation (ADP-Ag) (non response if >70%), Platelet reactivity
      index VASP (PRI VASP) (non response if >50%) and Verify Now Point-of-care assay
      (VN) (non response if PRU > 240 AU). RESULTS: Seventy consecutive patients were
      included. The rates of non-responders were respectively: 13% (n = 9) with the ADP
      Ag, 39% (n = 27) with the PRI VASP and 33% (n = 23) with the VN. We observed
      significant correlation between different platelet tests assessing clopidogrel
      response: r = 0.55 (p < 0.0001) for ADP-Ag and PRI VASP, r = 0.64 (p < 0.0001)
      for ADP-Ag and VN and r = 0.59 (p < 0.0001) for PRI VASP and VN. However, using
      the most common thresholds, the agreement between the difference tests was poor:
      0.35 for ADP-Ag and PRI VASP, 0.36 for ADP-Ag and VN and 0.46 for PRI VASP and
      VN. CONCLUSION: This study showed that assessment of platelet function inhibition
      by clopidogrel is highly test-specific. Indeed, our results demonstrated a poor
      agreement between different platelet assays and suggested that identification of
      clopidogrel non responders is test-dependent.

PMID- 20142120
TI  - Heart involvement in systemic sclerosis: evolving concept and diagnostic
      methodologies.
AB  - Heart involvement, including primary myocardial involvement, is very common in
      systemic sclerosis. There is strong evidence that primary myocardial involvement
      is related to repeat focal ischaemic injury causing subsequent irreversible
      myocardial fibrosis. Clinically evident cardiac involvement is recognized to be a
      poor prognostic factor; thus preclinical identification is highly encouraged. The
      severity of heart involvement has been confirmed recently. Echocardiography,
      including pulsed tissue Doppler echocardiography, is the cornerstone of routine
      heart assessment. Myocardial perfusion may be assessed by single photon emission
      computed tomography. If available, cardiac magnetic resonance imaging should be
      considered as it allows simultaneous measurement of ventricular volumes and
      function and myocardial perfusion, and assessment of possible inflammation and/or
      fibrosis. Biological variables, such as B-type natriuretic peptides, are highly
      relevant, valuable markers of global heart involvement in systemic sclerosis and
      should be considered for screening of patients and/or research purposes.

PMID- 20142121
TI  - Delayed right ventricular perforation with a pacemaker lead into subcutaneous
      tissues.

PMID- 20142122
TI  - Left ventricular hypertrophy: cardiac magnetic resonance may help differentiate
      amyloidosis from hypertrophic cardiomyopathy.

PMID- 20142123
TI  - Six-year status quo with fractional flow reserve.

PMID- 20142124
TI  - Silent embolization of a large left ventricular thrombus.

PMID- 20142126
TI  - Does medical student membership in the gold humanism honor society influence
      selection for residency?
AB  - OBJECTIVES: With the creation of the Gold Humanism Honor Society (GHHS) in 2002,
      the Arnold P. Gold Foundation established a mechanism for recognizing medical
      students who demonstrate exemplary humanism/professionalism/communication skills.
      Currently, 80 medical schools have GHHS chapters. Selection is based on peer
      nomination using a validated tool. The objective of this survey was to assess the
      percentage of residency program directors (PDs) who are aware of and are using
      GHHS membership as a residency selection tool. METHODS: Surgery (SURG) and
      internal medicine (IM) PDs in 4 United States regions were surveyed for
      familiarity with GHHS and perceived rank of GHHS membership relative to Alpha
      Omega Alpha (AOA) membership, class rank, medical student performance evaluation
      (MSPE), clerkship grade, and United States Medical Licensing Examination (USMLE)
      score, in evaluating an applicant's humanism/professionalism, service
      orientation, and fit with their program. Program demographics and familiarity
      with GHHS were also surveyed. RESULTS: The response rate was 56% (149
      respondents). IM PDs rated GHHS membership higher than did SURG PDs when
      evaluating professionalism/humanism and service orientation. PDs familiar with
      GHHS ranked membership higher when considering professionalism/humanism (4.1 vs
      3.2; p < 0.05) and service orientation (4.1 vs 2.9; p < 0.01). Familiarity with
      GHHS correlated with being an IM PD, residency based at teaching hospital, large
      residency program, knowledge of residents who were GHHS members, and having a
      GHHS chapter at their school (p < 0.01). Familiarity with GHHS was related to
      rankings of GHHS (professionalism/humanism F = 3.36; p < 0.05; service
      orientation F = 3.86; p < 0.05) more than the PDs' specialty was. In all, 157
      GHHS students (from all 4 United States regions) were also surveyed about the
      1197 interviews they had with residency PDs. They reported that although a few
      PDs were aware of GHHS, PDs of core medical specialties were more aware of GHHS
      than SURG PDs. CONCLUSIONS: IM PDs were more aware of GHHS (70%) than SURG PDs
      (30%). Awareness was related to the favorable ranking of GHHS as a selection
      criterion for humanism/professionalism/service orientation. PDs familiar with
      GHHS were from larger programs, were likely to know residents who were members,
      and were likely to think that GHHS membership predicted humanistic care.
      Membership in GHHS may set candidates apart from their peers and allow PDs to
      distinguish objectively the candidates who demonstrate compassionate medical
      care. Increased knowledge about the GHHS may therefore serve to be a useful
      adjunct for PDs when selecting medical students for their residency programs.

PMID- 20142127
TI  - Effect of the night float system on operative case volume for senior surgical
      residents.
AB  - PURPOSE: In response to the Accreditation Council for Graduate Medical Education
      (ACGME) mandated 80-hour workweek, the night float coverage model was one system
      created to comply with the work-hour restriction. However, concern has risen as
      to the operative case volume achieved with this model. The purpose of this study
      is to determine which system of call (night float vs traditional rotating call)
      provided the senior surgical resident with the greatest surgical case volume
      while in compliance with the 80-hour workweek. METHODS: A nonrandomized
      sequential study to evaluate the ACGME surgical operative logs (SOLs) for
      surgical chief residents at Memorial University Medical Center (MUMC), which is a
      level 1 trauma center, from 2006 to 2008 was conducted. The night float system
      (NFS) consisted of a PGY-4 or -5 assigned to in-house general surgery and trauma
      call from 6:00 pm to 6:00 am Monday through Friday morning and a 24-hour shift
      from 6:00 am on Sunday to 6:00 am Monday morning. Two months of night call
      rotations (nights) are performed each year per resident with the other 10 months
      devoted to daytime rotations (days). Conversely, the traditional rotating call
      schedule (TCS) placed each resident on-call every sixth night for a 30-hour
      period. The TCS required the resident to average approximately 3 weekday and 2
      weekend calls per month. The data examined include all cases on the ACGME SOL
      submitted by each PGY-4 and 5 residents over a 2-year span. Specific designation
      of cases between night and day rotations was evaluated while on the NFS, and the
      total cases volume performed on the NFS and the TCS were analyzed. RESULTS: An
      evaluation of the 2006-2007 (NFS) year demonstrates an average of 16 cases per
      month while on nights as compared with 20 cases per month while on day rotations.
      The caseload on the night rotation was less than day rotations at the PGY-4/5
      level. An analysis of the 2006-2007 (NFS) and 2007-2008 (TCS) for PGY-4/5
      residents revealed an average total caseload of 224 and 276, respectively. A
      statistically significant total case difference of 52 cases over the entire year
      between the 2 systems of call was appreciated. CONCLUSIONS: Because of the work
      hour restrictions, maximizing surgical education has become a necessity. With the
      various call systems used throughout general surgery programs, this study
      specifically compares a traditional 1-in-6 call schedule versus an NFS. Senior
      residents lost significant operative experience while operating under an NFS as
      compared with a TCS. Evidence suggests that the more hours spent by a chief
      resident during normal operative time elicits more operative experience.

PMID- 20142128
TI  - Factors correlated with surgery resident choice to practice general surgery in a
      rural area.
AB  - OBJECTIVE: General surgery workforce shortages in the rural United States are
      likely to worsen over the next decade. We sought to identify reasons that general
      surgery residency graduates choose rural versus urban practice. DESIGN:
      Questionnaires were sent to 1994 through 2008 graduates of all 4 Wisconsin
      surgery residency programs (2 university and 2 community). The 51-item
      questionnaire was designed to evaluate residency graduates' background,
      interests, and factors influencing their choice of practice type and location.
      Graduates were divided into 2 groups based upon the size of the communities in
      which they currently practice: rural (<50,000) or urban (>or=50,000). Data were
      analyzed using chi(2) tests; level of confidence was defined as p < 0.05.
      RESULTS: Forty-five percent (98/216) of surveys were completed. Factors
      associated with rural practice included attending a nonurban high school (p =
      0.001) or college (p = 0.001), having a spouse/partner who grew up in a nonurban
      area (p = 0.022), and interest in hunting birds (p = 0.010) or large game (p =
      0.001). Those choosing rural practice were more likely than their urban
      counterparts to have completed a rural clerkship during medical school (79% vs.
      37%, p = 0.001). They were also more likely to have chosen a surgical residency
      program committed to rural training (p = 0.046). Graduates in rural practice more
      often cited "broad scope of practice" as an important reason for their decision.
      Both rural and urban surgeons reported similar rates of medical student teaching
      but urban surgeons were more likely to teach surgical residents (p = 0.001) and
      to have completed fellowship training (p = 0.001). CONCLUSIONS: General surgery
      residency graduates and their spouses who choose rural practices are more likely
      than those selecting urban practices to have rural backgrounds and interests.
      Completing a rural clerkship during medical school and choosing a residency
      program committed to rural general surgery preparation are strongly correlated
      with rural practice. These findings may help formulate strategies to increase
      recruitment and retention of rural general surgeons.

PMID- 20142129
TI  - Factors influencing residency choice of general surgery applicants--how important
      is the availability of a skills curriculum?
AB  - OBJECTIVE: The objective of this study was to assess the factors that impact
      residency choice by general surgery applicants and the importance of the
      availability of skill curricula. METHODS: Fourth-year medical students (n = 104)
      interviewing for a general surgery position in an academic medical center
      voluntarily completed an anonymous survey detailing questions about the factors
      that influenced their choice of a residency program. Applicants were asked to
      rank in order of importance 14 factors potentially influencing their decision
      making and to address specifically the value of skills training. Data are
      reported as medians (range). RESULTS: The applicants' median age was 26 (range,
      24-35) years; 44% were women, and the prior simulator exposure was 1 (range, 0
      90) hour. The factors influencing the choice of residency in order of importance
      were the quality of life of current residents, the volume and variety of cases,
      and the quality of the curriculum (medians, 3-4), followed by the reputation of
      the institution and the program director, the location, and mentor advice
      (medians, 6-8); and the presence of expertise in areas of interest, the
      availability of a skills curriculum, the academic versus private designation, the
      efficiency of the hospital, and the size of residency (medians, 9-10). Women were
      more likely than men to rank lifestyle higher. Applicants' decision making was
      influenced positively in 92% by the presence of an organized skills curriculum.
      CONCLUSIONS: The main determinants of the applicants' choice of a general surgery
      program are the quality of life of the residents and the anticipated clinical
      experience and curriculum quality. The availability of organized skills curricula
      is low in the applicant priorities, but it does influence their decision-making
      process. These findings may help program directors to optimize their residency
      curriculum and interviewing process.

PMID- 20142130
TI  - Four-year experience with a regional program providing simulation-based
      endovascular training for vascular surgery fellows.
AB  - PURPOSE: High-fidelity procedure simulation has been found useful for training
      vascular surgery residents in endovascular procedures, but the costs of
      acquiring, maintaining, and operating simulators represent a barrier to routine
      use of endovascular simulation in vascular surgery programs. Providing simulation
      training opportunities through regional centers may make simulation more cost
      effective, but the costs and benefits of this approach have not been reported
      previously. We reviewed participation costs in a regional simulation program to
      provide a benchmark for comparison with other training options. METHODS:
      Simulation-based training was offered annually from 2004 to 2007 to the 11
      vascular surgery fellowships in Washington, Oregon, California, Arizona, and
      Utah. Participation was at the discretion of the program directors and fellows.
      Sessions were designed to offer individualized, hands-on training with 2-4
      participants per 2-day session. SimSuite (Medical Simulation Corporation, Denver,
      Colorado) simulators were used. RESULTS: During the 4-year period, participation
      by invited programs averaged 75%. Ten of 11 programs in the western United States
      region participated, with 34 fellows participating during the 4 years of the
      program. In addition, 2 program directors or faculty attended sessions to
      participate as learners, and 8 other individuals were allowed to participate
      (including 7 senior surgery residents and 1 vascular surgery fellow from out of
      the region). The average participant costs for travel, which include
      transportation, lodging, and meals, were $571. Simulation facility expenses,
      which included use of the simulator, computer-based training modules, and
      instructional support by an educational specialist, averaged $1055 per
      participant. Surgical faculty spent 12 hours per 2-day session instructing and in
      other direct educational activities. Costs for this time were not calculated
      separately. CONCLUSIONS: Vascular surgery fellows' participation in simulation
      training at regional centers offers program directors a lower cost alternative
      for providing high-fidelity simulation training, compared with acquiring and
      operating an endovascular procedure simulator at their individual institutions.

PMID- 20142131
TI  - Graduate medical education as the driver for quality improvement and patient
      safety: a national initiative of independent academic medical centers.

PMID- 20142132
TI  - Implementation of an "after hours" resident educational program in a general
      surgery residency: a paradigm for increasing formal didactic training outside of
      the hospital setting in the era of the 80-hour workweek.
AB  - INTRODUCTION: Residency programs have been forced to curtail many educational
      activities to comply with duty-hour restrictions. We describe an "after hours"
      educational program as a forum to provide small-group education customized for
      each training level to compliment our formal curriculum. METHODS: Sessions within
      each general surgery specialty were organized such that 1 session each month was
      open to either junior (R1 and R2) or senior (R3-R5) trainees and hosted by
      surgical faculty. Attendance was optional and limited to 15 residents per session
      with the format determined by the hosting faculty. Participants completed a
      postsession survey. RESULTS: Fourteen sessions were held during the 2008-2009
      academic year. All sessions were >90% subscribed within 1 week of announcement
      and attendance was 88%. The average session duration was 2.6 +/- 0.4 hours.
      Junior resident sessions focused on preparing R1 and R2 residents to handle
      common consult questions; senior resident sessions were modeled as "mock oral
      boards." Resident and faculty responses to the postsession questionnaire were
      similar and favorable with respect to the educational value of this format.
      CONCLUSIONS: There is enthusiasm among faculty and trainees to provide small
      group, level-specific educational programs outside of the hospital setting and
      the 80-hour workweek. Such a program is easily implemented, highly effective, and
      well received. This format has the added benefit of improving interaction between
      faculty and residents and increasing the camaraderie of a surgical training
      program.

PMID- 20142133
TI  - Novel hybrid objective structured assessment of technical skills/objective
      structured clinical examinations in comprehensive perioperative breast care: a
      three-year analysis of outcomes.
AB  - PURPOSE: Objective Structured Assessment of Technical Skills (OSATS) and
      Objective Structured Clinical Examinations (OSCE) are common tools used to
      objectively evaluate surgical residents. In 2005, our institution presented a
      novel hybrid OSATS/OSCE, which we renamed the Objective Structured Clinical
      Assessment (OSCA), encompassing all 6 core competencies regarding comprehensive
      care of the breast care patient. This study presents an analysis of the effects
      of a compulsory, comprehensive OSCA on our residents' competence in this index
      learning category. METHODS: Completed breast OSCA, Accreditation Council for
      Graduate Medical Education (ACGME) operative logs, and Report D of the American
      Board of Surgery in Training Examination (ABSITE) were collected for 24 senior
      level residents. The OSCA was implemented for post graduate year (PGY)-3
      residents in the 2003-2004 year. Data were also collected for an equal number of
      residents before the OSCA. Competence of residents was evaluated using the
      procedure-based OSCA that encompasses the 6 core competencies, completed for each
      resident by a specialty breast surgeon. Next, ACGME operative logs for graduating
      seniors were analyzed. Finally, breast care questions were identified from Report
      D. The number of residents scoring incorrectly on these questions was divided by
      the total number of resident-questions to yield a percent incorrect for each
      group. Similarly, the percent of total incorrect ABSITE examination questions was
      calculated, assessing overall group improvement. RESULTS: All assigned residents
      achieved competence in all designated categories of the OSCA. Since the OSCA, the
      average number of breast cases in our program has risen from a mean of 102 cases
      to 124 cases per graduating senior. ABSITE data showed 264 resident-questions
      before the OSCA, with 26.5% incorrect responses. After OSCA, there were 252
      resident-questions, with 18.25% incorrect. This represents a significant decrease
      (p < 0.05) of incorrect responses to breast questions on the ABSITE. Before the
      OSCA, there were 2139 total resident-questions with 25.28% wrong responses and
      after, there were 2111 resident-questions with 23.97% wrong responses,
      representing no significant difference (p > 0.05) in incorrect responses on the
      entire examination. CONCLUSIONS: Our data show consistent competence of residents
      in breast disease as evaluated by the OSCA, an increase in numbers of breast
      cases, and a decrease in incorrect responses on breast-related ABSITE questions.
      We believe a comprehensive, complete care OSCA represents a valuable learning
      tool for residents to increase their competence and improve their outcomes in
      breast care. We believe that comprehensive OSCAs will be necessary tools to
      evaluate resident competence and should be implemented in all areas of general
      surgery.

PMID- 20142134
TI  - Refining the evaluation of operating room performance.
AB  - PURPOSE: An accurate and consistent evaluation of resident operative performance
      is necessary but difficult to achieve. This study continues the examination of
      the Southern Illinois University (SIU) operative performance rating system (OPRS)
      by studying additional factors that may influence reliability, accuracy, and
      interpretability of results. METHODS: OPRS evaluations of surgical residents by
      faculty at SIU, from 2001 to 2008, were analyzed for the most frequently rated
      procedures to determine (1) the elapsed time from the procedure until completion
      of rating, (2) the patterns in responses of procedure-specific and global
      surgical skills items, and (3) whether particular evaluating surgeons differed in
      their stringency of ratings of resident operative performance. RESULTS: In all,
      566 evaluations were analyzed, which consisted of open colectomy (n = 125), open
      inguinal hernia (n = 103), laparoscopic cholecystectomy (n = 199), and excisional
      biopsy (n = 139). The number of residents evaluated per training level (PGY)
      ranged from 88 to 161. The median time to completion of evaluations was 11 days,
      9 hours. The quickest evaluation was 18 hours after assignment. Most were
      completed within 4.5 to 22 days. Procedure-specific and global scale scores
      resulted in similar rank-ordering of performances (single-measure intraclass
      correlation using the consistency model = 0.88; 95% confidence interval [CI] =
      0.87-0.90) and similar absolute OPRS scores (single-measure intraclass
      correlation using the consistency model = 0.89; 95% CI, 0.87-0.90). Evaluating
      surgeons differed in stringency of ratings across procedures (average difference
      = 1.4 points of 5 possible points). Resident performance improved with increasing
      PGY level for all 4 procedures. CONCLUSIONS: Substantial time elapses between
      performance in the operating room and the completion of the evaluation. This
      raises the question of whether surgeons remember the nuances of the procedure
      well enough to rate performance accurately. The item type used for rating does
      not affect the absolute rating assigned or the rank ordering of the performance.
      Differences in stringency of evaluators indicate the need for multiple resident
      performance observations by multiple surgeons. These findings are the foundation
      for an upcoming multi-institutional trial.

PMID- 20142135
TI  - Revisiting the rotating call schedule in less than 80 hours per week.
AB  - PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) work
      hour restrictions have prompted many surgical training programs to adopt a night
      float resident coverage system (NF). Dissatisfaction with NF prompted us to
      transition to a rotating junior resident call model (Q4) with 24-hour call shifts
      at the outset of the 2007-2008 academic year. We performed a prospective study to
      determine the influence of this transition on resident education, morale, and
      quality of life, as well as on ACGME work rule compliance and American Board of
      Surgery In-Training Examination (ABSITE) scores. METHODS: Residents were surveyed
      after 1 year of NF and again 1 year after the introduction of Q4. Responses to a
      series of statements about the influence of the call model (NF or Q4) on
      educational opportunities and morale were solicited. The survey used a 5-point
      Likert response scale (1 = complete disagreement to 5 = complete agreement).
      Median values of participant responses were calculated and compared using the
      Wilcoxon rank-sum test. Compliance with ACGME work rules, ABSITE scores, and
      operative case logs from the 2006-2007 and 2007-2008 academic years were also
      compared. RESULTS: Residents were significantly more enthusiastic about Q4
      compared with NF, particularly when asked about the influence these systems had
      on morale (median response = 4.0 [Q4] compared with 2.0 [NF]; p = 0.001) and
      engagement of residents by the teaching faculty (median response = 4.0 [Q4]
      compared with 1.0 [NF]; p = 0.001). Case logs revealed a similar operative
      experience for first-year residents irrespective of the call schedule (p = 0.51).
      Excellent compliance with ACGME work rules was maintained as reflected by the
      percentage of monthly 80-hour violations per resident months worked (3% [Q4]
      compared with 0.7% [NF]). No difference was observed in the ABSITE scores of
      first-year residents (a mean percentile point increase of 1 was found after the
      introduction of Q4). CONCLUSIONS: Educational opportunities, compliance with
      ACGME work rules, and ABSITE scores can be preserved despite a transition from NF
      to Q4. Residents greatly prefer a rotating call schedule.

PMID- 20142136
TI  - The effectiveness of grand rounds lectures in a community-based teaching
      hospital.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of weekly
      didactic grand rounds presentations. DESIGN: From 26 consecutive grand rounds
      presentations from July 2007 to March 2008, 2 questions were created from each
      lecture. A 52-question multiple choice test was administered 2 weeks after the
      completion of the last presentation. SETTING: A tertiary care institution with an
      accredited surgical residency program. PARTICIPANTS: Attending surgeons,
      residents, midlevel providers, and medical students participated in the multiple
      choice test. RESULTS: A total of 58 participants completed the test. The mean
      score was 41.5% (range, 12-69%). The senior residents had the highest mean score
      on the test with 51.0% (p = 0.021). With regard to global versus specific
      questions, there was no significant difference between the mean percentage of
      correct answers (41.7% vs 41.3%, respectively, p = 0.79). The great majority
      (76.5%) of participants indicated that they preferred to have grand rounds given
      by "distinguished guest speakers." The mean score on presentations by guest
      speakers, however, was slightly lower than for other presenters (40.7% vs 42.2%,
      p= 0.37). Questions from presentations by resident physicians were answered
      correctly significantly more often than presentations by attending surgeons
      (45.9% vs 39.6%, p = 0.001). Trauma and burn are considered areas of focus for
      this surgical residency. There was no significant difference between mean score
      on topics related to trauma and burn compared with other topics (40.6% vs 41.8%,
      p = 0.50). Attendance had very little correlation with scores on the test
      (correlation coefficient, 0.004). CONCLUSIONS: Approximately 40% of material
      presented at grand rounds was retained within a 9 month period. Although this
      number seems low, this information was recalled without preparation. Despite the
      preference for distinguished guest speakers, there was no significant additional
      gain in knowledge from their expertise. Presentations from senior residents were
      the most successful in conveying information.

PMID- 20142137
TI  - The utility of endovascular simulation to improve technical performance and
      stimulate continued interest of preclinical medical students in vascular surgery.
AB  - OBJECTIVE: New training paradigms in vascular surgery allow for early
      specialization out of medical school. Surgical simulation has emerged as an
      educational tool for trainees to practice procedures in a controlled environment
      allowing interested medical students to perform procedures without compromising
      patient safety. The purpose of this study is to assess the ability of a
      simulation-based curriculum to improve the technical performance and interest
      level of medical students in vascular surgery. DESIGN: Prospective observational
      cohort study of medical student performance. SETTING: Academic medical center.
      PARTICIPANTS: Forty-one medical students (23 first year, 15 second year, 3 other)
      enrolled in a vascular surgery elective course. Students completed a survey of
      their interests and performed a renal stent procedure on an endovascular
      simulator (pretest). The curriculum consisted of didactic teaching and weekly
      mentored simulator sessions and concluded with a final renal stent procedure on
      the simulator (posttest). Objective procedural measures were determined during
      the pre- and posttest by the simulator, and subjective performance was graded by
      expert observers utilizing a structured global assessment scale. After the
      course, the students were surveyed as to their opinions about vascular surgery as
      a career option. Finally, 1 year after the course, all students were again
      surveyed to determine continued interest in vascular surgery. RESULTS: The
      objective and subjective criteria measured on the simulator and structured global
      assessment scale significantly improved from pre- to posttest in terms of
      performer technical skill, patient safety measures, and structured global
      assessments. Before beginning the course, 8.5% of the students expressed high
      interest in vascular surgery, and after completing the course 70% were seriously
      considering vascular surgery as a career option (p = 0.0001). More than 95% of
      the students responded that endovascular simulation increased their knowledge and
      interest in vascular surgery. In the 1-year follow-up survey (n = 23 medical
      students), 35% had already entered their clinical years. Seventy percent of the
      students were still considering vascular surgery, while several other career
      options were still popular including the surgical subspecialties (70%),
      interventional cardiology (57%), and interventional radiology (48%). Most
      respondents indicated the major reasons for continued interest in vascular
      surgery were the ability to practice endovascular procedures on the simulator
      (100%) and mentorship from vascular surgery faculty (78%). CONCLUSIONS: The use
      of high fidelity endovascular simulation within an introductory vascular surgery
      course improves medical student performance with respect to technical skill,
      patient safety parameters, and global performance assessment. Mentored exposure
      to endovascular procedures on the simulator positively impacts long term medical
      student attitudes towards vascular surgery. Simulator-based courses may have the
      potential to be an important component in the assessment and recruitment of
      medical students for future surgical training programs.

PMID- 20142138
TI  - Understanding accreditation council for graduate medical education (ACGME)
      guidelines: resident and program director interpretation of work-hour
      restrictions.
AB  - PURPOSE: All residency programs must comply with the Accreditation Council for
      Graduate Medical Education (ACGME) work-hour guidelines, but compliance requires
      accurate interpretation of the rules. We previously surveyed the residents and
      program directors of general surgery residency programs and found significant
      discordance between what program directors and residents considered violations.
      Our current study expands our research to include family medicine and emergency
      medicine residents and program directors. This study aims to identify
      discrepancies of work-hour guideline interpretation within and between the
      specialties. METHODS: We created 10 scenarios related to work-hour issues. The
      ACGME reviewed them and judged whether a violation occurred in each scenario.
      From these scenarios, an Internet-based survey was generated and distributed
      electronically to every family medicine and emergency medicine residency in the
      United States. (Surgery programs were previously surveyed from March 1 through
      May 21, 2007 with the same scenarios.) Responses were collected anonymously via
      our Internet-based survey database from March 1 through May 17, 2008. All
      respondents were asked to identify themselves as either a program director or a
      resident. After reading each scenario, participants were asked to answer either
      "yes," "no," or "maybe/not sure." The option of "maybe/not sure" was in place to
      discourage guessing; those responses were not included in our analysis. After the
      data were collected, we calculated the percent of respondents that answered "yes"
      or "no" for each of the 10 scenarios related to work-hour issues. The results
      from within specialties (program directors vs residents) and between specialties
      (general surgery, family medicine, emergency medicine) were compared. RESULTS:
      There were a total of 883 respondents (334 general surgery, 374 family medicine,
      and 175 emergency medicine). Respondents identified themselves as program
      directors (97), assistant program directors (21), or residents (765).
      Statistically significant differences were identified in the responses of program
      directors and residents within and between specialties. CONCLUSIONS: Based on the
      scenarios we presented, there was a difference in interpretation between
      residents and program directors. There was even disagreement among program
      directors of different specialties on the interpretation of some of the
      scenarios. This finding reveals an ambiguity in the work-hour restrictions. We
      conclude that the ACGME-mandated work-hour guidelines are confusing and not
      universally understood. This problem is compounded by the cross-training with
      "off-service" residents from other specialties such as family medicine and
      emergency medicine. Hence, enforcement of the work-hour restrictions may be
      problematic, despite the best intentions and sincere effort of directors and
      residents to interpret the rules.

PMID- 20142139
TI  - Use of text messaging to enhance compliance with the accreditation council for
      graduate medical education resident duty hour requirements.
AB  - PURPOSE: Recently, the Accreditation Council for Graduate Medical Education
      (ACGME) has developed and enforced a complex set of regulations limiting resident
      duty hours (RDHs). One potential method to comply with these stringent
      regulations and better document resident work hours would be to use text message
      (TM)/short message service (SMS), allowing rapid, inexpensive, and interactive 2
      way delivery of information. The purpose of this study was to document the
      successful implementation of TM to enhance compliance with the ACGME RDH
      regulations. METHODS: Our TM system uses TSHEETS (TS; Meridian, Ohio), which is
      an online time- and labor-management service. After our general surgical
      residents were registered with the system, the documentation of entry into
      (texting "t start" to a predetermined number) and exit out of (texting "t stop"
      to the same number) the hospital could easily be accomplished. The goals of this
      pilot study were to determine (1) the feasibility of implementing a program such
      as this and (2) if use of such a program was associated with high resident
      satisfaction and improved compliance. RESULTS: We registered 39 residents with
      TS. Within 3 days, compliance rose from 76.9% to 96.2%. After implementation of
      TM reminders, compliance increased to 100%. A time-tracking resident satisfaction
      survey was distributed after 8 weeks of data collection. Twenty six of 39 (67%)
      residents participated in the survey, with 25 (96%) being more satisfied with the
      current application as compared with either of the previous (manual or swipe
      card) systems, specifically regarding ease of use and overall ACGME RDH
      compliance. Self-reported resident scores of their ability to be compliant with
      ACGME RDH before versus after implementation increased from 47% to 75% (p <
      0.05). CONCLUSIONS: We were able to implement successfully a novel technique for
      ACGME RDH documentation and compliance in a general surgery residency program
      through the use of TM; this approach employed a state-of-the-art time-tracking
      method that was associated with high levels of resident work-hour compliance and
      overall satisfaction.

PMID- 20142140
TI  - What do surgical nurses know about surgical residents?
AB  - OBJECTIVE: A fundamental premise of establishing collaborative relationships
      between residents and nurses is a basic understanding of the attributes of each
      group. The intent of this study was to determine what surgical nurses know about
      surgical residents. DESIGN: A piloted survey tool was administered to a cross
      section of nurses working in 3 surgical intensive care units, a surgical
      intermediate unit, and 2 general surgical floors. Surgical residents completed
      the same survey tool. The percentage of residents giving the most frequent
      response was compared with the percentage of nurses giving the same response.
      SETTING: A university, teaching hospital. PARTICIPANTS: One hundred twenty-four
      of 129 surgical nurses and 24 of 25 surgical residents who completed the survey
      tool. RESULTS: The response rate for nurses on the 2 survey days was 94%, or 54%
      of all surgical nurses employed by the hospital, and 96% for residents. The
      nurses surveyed were equally distributed between the units. Ninety-nine percent
      of nurses did not have a surgical resident as a significant other, 55% of nurses
      had greater than 5 years experience, and 95% were licensed registered nurses.
      Seventy-eight percent of nurses correctly indicated that a medical doctorate is
      the highest degree required to start residency (p = 0.01), but only 57%
      accurately identified the length of surgical residency (p = 0.02). Nurses
      perceived residents devoted less time to patient care (p < 0.01) and more time to
      studying (p < 0.01). Forty percent of nurses do not think interns are legally
      physicians (p < 0.01) or hold a medical license (p < 0.01). Forty percent of
      nurses are aware of the 80-hour work week restriction (p < 0.01). Eighteen
      percent of nurses have the perception that residents are not allowed to perform
      bedside procedures without an attending physician present (p = 0.03), while 56%
      have the perception that residents are not allowed to perform any part of an
      operation without an attending physician (p < 0.01). There is a misperception
      among 32% of nurses that residents pay tuition for residency (p < 0.01), while
      only 52% accurately identified the range of a resident's salary (p = 0.01) and
      11% the amount of resident debt (p < 0.01). CONCLUSIONS: Despite the importance
      of the collaborative relationship in surgical patient care, surgical nurses have
      a limited understanding of surgical residents. Educating nurses about the
      education, roles, and responsibilities of surgical residents might improve
      collaborative relationships and ultimately patient care.

PMID- 20142141
TI  - Visual learning: harnessing images to educate residents optimally.
AB  - Surgical educators are confronted with outdated models of education and less time
      for teaching. Digital images present an opportunity for a new method of
      education. In this method, students are presented with a series of key images,
      each representing an important teaching point (radiographs, patient external
      images, operative images, and histopathology images) and asked to construct a
      corresponding case presentation. In this fashion, the traditional presentation is
      disassembled and the learner is responsible for teaching his or her colleagues.
      By incorporating surgical images into the teaching process, the teacher enhances
      insight and learning. In addition, by prompting the students to add creative
      elements to the thought process for diagnosis and management, the teaching format
      can be a dynamic and interactive process.

PMID- 20142142
TI  - Professionalism in Kurosawa's medical dramas.
AB  - Film director Akira Kurosawa (1918-1998) portrayed doctors and patients in 4
      films that spanned the most productive phase in his career: Drunken Angel, The
      Quiet Duel, Ikiru, and Red Beard. Observing death and destruction during the
      Second World War and the social disintegration that followed it in Japan,
      Kurosawa viewed the world as a dispiriting, dangerous, and chaotic place. His
      response was an optimistic and humanist view that life's meaning lies in the
      service to others. Because his main characters are doctors and patients, the
      films have a connection to today's medical community trying to define a modern
      concept of professionalism and what it means to be a physician.

PMID- 20142143
TI  - Introduction to the special issue on analysis, design, and synthesis of
      biological systems using advanced manipulation.

PMID- 20142144
TI  - Atomic force microscopy imaging of supramolecular organization of hyaluronan and
      its receptor CD44.
AB  - Hyaluronan is a major component of extracellular matrix and involved in a variety
      of important biological processes such as cell motility, proliferation,
      differentiation, and survival. However, the structure of hyaluronan and the mode
      of interaction between hyaluronan and its receptor remain to be fully elucidated.
      Here, we visualized directly the structure of hyaluronan by nanoscale imaging
      using atomic force microscopy (AFM), and analyzed the pattern of interaction with
      its cell surface receptor CD44. We observed by AFM that hyaluronan formed
      honeycomb-like network structures, to which the recombinant protein of CD44
      extracellular domain intensively adhered. The pattern of the meshwork varied with
      the concentration of hyaluronan and also with its molecular weight. These
      observations suggest that the network structure might account for the properties
      of hyaluronan of being like an elastic gel at high concentration, and that the
      structure varying in relation to the molecular weight may cause the difference in
      the biological activities of the hyaluronan.

PMID- 20142145
TI  - Microorifice-based high-yield cell fusion on microfluidic chip: electrofusion of
      selected pairs and fusant viability.
AB  - Microorifice-based fusion makes use of electric field constriction to assure high
      yield one-to-one fusion of selected cell pairs. The aim of this paper is to
      verify feasibility of high-yield cell fusion on a microfluidic chip. This paper
      also examines viability of the fusant created on the chip. We fabricated a
      microfluidic chip to fuse selected cell pairs and to study postfusion behavior.
      We used a self-forming meniscus-based fabrication process to create microorifice
      with a diameter of 2-10 microm on the vertical walls in a microfluidic channel.
      When 1 MHz was applied to electrodes located on both sides of the microorifice,
      dielectrophoretic force attracted the cells toward microorifice to form a cell
      pair. Once the cells get into contact, fusion pulse was applied. Real time
      imaging of cells during fusion and cytoplasmic dye transfer between cells
      indicated success of cell fusion. We found that when high frequency voltage for
      dielectrophoresis was swept from 1 MHz to 10 kHz in 100 micros, cell fusion was
      initiated. The effective electric field strength was 0.1-0.2 kV/cm. We analyzed
      viability by imaging fusant going into cell division phase after 48 h of
      incubation. We conclude that fabricated microfluidic chip is suitable for high
      yield one-to-one fusion and creation of viable fusants. This technology should be
      a useful tool to study fusion phenomena and viability of fusants, as it allows
      imaging of the cells during and after the fusion.

PMID- 20142146
TI  - A rapid microfluidic switching system for analysis at the single cellular level.
AB  - Analysis of cellular responses to chemicals at high spatiotemporal resolution is
      required for precise understanding of intracellular signal transduction. Here, we
      demonstrated a novel method for applying different solutions to a part of or all
      of a cell at high spatiotemporal resolution. We fabricated a microfluidic device
      using polydimethylsiloxane, and the sharp interface between the two solution
      streams flowing in the channel was used for the application of different
      solutions. We constructed a computer-controlled system to control the interface
      movement precisely, rapidly, and reproducibly during positioning, and spatial and
      temporal resolutions attained were 1.6 mum and 189 ms, respectively. We then
      applied the present system to the analysis of intracellular responses to
      chemicals. We were able to measure [Ca (2+)] (i) increases within 500 ms, when
      one laminar stream covered a part of the cell. This method can be used as a
      generic platform to investigate responses against drugs at the single cell level.

PMID- 20142147
TI  - On-chip single embryo coculture with microporous-membrane-supported endometrial
      cells.
AB  - In vitro culture (IVC) of the mammalian embryo is an essential technique in
      reproductive technology and other related life science disciplines. Although
      embryos are usually cultured in groups, a single embryo culture has been highly
      desired for IVC to investigate developmental processes. In this study, we
      proposed and developed the first single embryo coculture device, which allows
      making an array of a single embryo coculture with endometrial cells by
      controlling the culture environment in a microfluidic device. To realize this
      concept, we investigated three key issues: selection of a culture medium for the
      embryo coculture with endometrial cells using a mouse embryo and endometrial
      cells, evaluation of an on-microporous-membrane coculture of endometrial cells
      and an embryo to control the polarization of endometrial cells on the membrane,
      and evaluation of the coculture of endometrial cells and the embryo in the
      microfluidic device. We successfully obtained an array of a single coculture of
      embryo with endometrial cells in a microfluidic device. This concept will open
      and enhance the management of an individual embryo for assisted reproductive
      technology, livestock breeding, and fundamental stage research by further
      development.

PMID- 20142148
TI  - Fabrication and evaluation of reconstructed cardiac tissue and its application to
      bio-actuated microdevices.
AB  - In this paper, we proposed to utilize a reconstructed cardiac tissue as
      microactuator with easy assembly. In a glucose solution, cardiomyocytes can
      contract autonomously using only chemical energy. However, a single cardiomyocyte
      is not enough to actuate a microrobot or a mechanical system. Though the output
      power will increase by using multiple cardiomyocyte, it is difficult to assemble
      those cardiomyocyte to predefined positions one-by-one using a micromanipulator.
      Reconstructed cardiac tissue not only will enable researchers to assemble the
      cells easily and but also has a potential to improve the contractile ability. To
      realize a bio-actuator in this paper, we reconstructed a microcardiac tissue
      using an extracellular matrix, and their displacements, displacement frequency,
      contractile force, and lifetime of the reconstructed cardiac tissue were
      evaluated. Electrical and pharmacological responses of the reconstructed cardiac
      tissue were also evaluated. Finally, a bioactuator, a primitive micropillar
      actuator, was fabricated and applicability of the reconstructed cardiac tissue
      for bioactuators was evaluated.

PMID- 20142149
TI  - Stable reconstruction of piecewise continuous plane stratified biological tissues
      via electrical impedance tomography.
AB  - Image reconstruction in electrical impedance tomography is, generally, an ill
      posed nonlinear inverse problem. Regularization methods are widely used to ensure
      a stable solution. Herein, we present a case study, which uses a novel electrical
      impedance tomography method for reconstruction of layered biological tissues with
      piecewise continuous plane-stratified profiles. The algorithm implements the
      recently proposed reconstruction scheme for piecewise constant conductivity
      profiles, utilizing Legendre expansion in conjunction with improved Prony method.
      It is shown that the proposed algorithm is capable of successfully reconstructing
      piecewise continuous conductivity profiles with moderate slop. This
      reconstruction procedure, which calculates both the locations and the
      conductivities, repetitively provides inhomogeneous depth discretization, i.e.,
      the depths grid is not equispaced. Incorporation of this specific inhomogeneous
      grid in the widely used mean least square reconstruction procedure results in a
      stable and accurate reconstruction, whereas, the commonly selected equispaced
      depth grid leads to unstable reconstruction. This observation establishes the
      main result of our investigation, highlighting the impact of physical phenomenon
      (the image series expansion) on electrical impedance tomography, leading to a
      physically motivated stabilization of the inverse problem, i.e., an inhomogeneous
      depth discretization renders an inherent regularization of the mean least square
      algorithm. The effectiveness and the significance of inhomogeneous discretization
      in electrical impedance tomography reconstruction procedure is further
      demonstrated and verified via numerical simulations.

PMID- 20142150
TI  - Mathematical modeling of CSF pulsatile hydrodynamics based on fluid-solid
      interaction.
AB  - Intracranial pressure (ICP) is derived from cerebral blood pressure and
      cerebrospinal fluid (CSF) circulatory dynamics and can be affected in the course
      of many diseases. Computer analysis of the ICP time pattern plays a crucial role
      in the diagnosis and treatment of those diseases. This study proposes the
      application of Linninger et al.'s [IEEE Trans. Biomed. Eng., vol. 52, no. 4, pp.
      557-565, Apr. 2005] fluid-solid interaction model of CSF hydrodynamic in
      ventricular system based on our clinical data from a group of patients with brain
      parenchyma tumor. The clinical experiments include the arterial blood pressure
      (ABP), venous blood pressure, and ICP in the subarachnoid space (SAS). These data
      were used as inputs to the model that predicts the intracranial dynamic
      phenomena. In addition, the model has been modified by considering CSF pulsatile
      production rate as the major factor of CSF motion. The approximations of
      ventricle enlargement, CSF pressure distribution in the ventricular system and
      CSF velocity magnitude in the aqueduct and foramina were obtained in this study.
      The observation of reversal flow in the CSF flow pattern due to brain tissue
      compression is another finding in our investigation. Based on the experimental
      results, no existence of large transmural pressure differences were found in the
      brain system. The measured pressure drop in the ventricular system was less than
      5 Pa. Moreover, the CSF flow pattern, ICP distribution, and velocity magnitude
      were in good agreement with the published models and CINE (phase-contrast
      magnetic resonance imaging) experiments, respectively.

PMID- 20142151
TI  - Analysis of fractionated atrial fibrillation electrograms by wavelet
      decomposition.
AB  - This study introduces the use of wavelet decomposition of unipolar fibrillation
      electrograms for the automatic detection of local activation times during complex
      atrial fibrillation (AF). The purpose of this study was to evaluate this
      technique in patients with structural heart disease and longstanding persistent
      AF. In 46 patients undergoing cardiac surgery, unipolar fibrillation electrograms
      were recorded from the right atrium, using a mapping array of 244 electrodes. In
      25 patients with normal sinus rhythm, AF was induced by rapid pacing, whereas 21
      patients were in persistent AF. In patients with longstanding AF, the atrial
      electrograms showed a high degree of fractionation. In each patient, 12 s of AF
      were analyzed by wavelet transformation (15 scales). The finest scales (1-7) were
      used to reconstruct a "local" fibrillation electrogram, whereas with the coarse
      scales (9-15), a far-field signal was generated. With these local and far-field
      electrograms, the "primary" fibrillation potentials, due to wave propagation
      underneath the electrode, could be distinguished from double potentials and
      multiple components generated by remote wavefronts. Wavelet transformation
      resulted in AF histograms with a closely gaussian distribution and the
      automatically generated activation maps showed a good resemblance with
      fibrillation maps obtained by laborious manual editing. A special chaining
      algorithm was developed to detect multiple components in fractionated
      electrograms. The degree of fractionation showed a positive correlation with the
      complexity of fibrillation, thus providing an objective quantification of the
      degree of electrical dissociation of the atria. Wavelet transformation can be a
      useful technique to detect the primary potentials and quantify the degree of
      fractionation of fibrillation electrograms. This could enable real-time mapping
      of complex cases of human AF and classification of the underlying
      electropathological substrate.

PMID- 20142152
TI  - PTT variability for discrimination of sleep apnea related decreases in the
      amplitude fluctuations of PPG signal in children.
AB  - In this paper, an analysis of pulse transit time variability (PTTV) during
      decreases in the amplitude fluctuations of pulse photoplethysmography signal
      (PPG) (DAP) events for obstructive sleep apnea syndrome (OSAS) screening is
      presented. The temporal evolution of time-frequency PTTV parameters during DAP
      was analyzed. The results show an increase in the sympathetic activity index low
      frequency component (LF) during DAP for PTTV (85%) significantly higher than for
      heart rate variability (HRV) (33%), (p < 10(-13)). However, decreases in
      parasympathetic activity produce lower decrements in high-frequency component
      (HF) indexes for PTTV (18%) than for HRV (22%). Thus, PTTV reflects sympathetic
      changes more clearly than HRV. A clinical study was carried out. DAP events were
      classified as apneic or nonapneic using a linear discriminant analysis from the
      PTTV indexes. The ratio of DAP events per hour r (DAP), the ratio after filtering
      based on HRV indexes r (HRV) (DAP), or on PTTV indexes r (PTTV) (DAP), were
      computed. The results show an accuracy of 75% for r (PTTV) (DAP) (14% increase
      with respect to r (DAP) and 5% increase with respect to r (HRV) (DAP)), a
      sensitivity of 81.8%, and a specificity of 73.9% when classifying 1-h
      polysomnographic excerpts as OSAS or normal. These results suggest that the
      combination of DAP and PTTV could be better alternative for sleep apnea screening
      using PPG with the added benefit of its low cost and simplicity.

PMID- 20142153
TI  - Adaptive real-time bioheat transfer models for computer-driven MR-guided laser
      induced thermal therapy.
AB  - The treatment times of laser induced thermal therapies (LITT) guided by
      computational prediction are determined by the convergence behavior of partial
      differential equation (PDE)-constrained optimization problems. In this paper, we
      investigate the convergence behavior of a bioheat transfer constrained
      calibration problem to assess the feasibility of applying to real-time patient
      specific data. The calibration techniques utilize multiplanar thermal images
      obtained from the nondestructive in vivo heating of canine prostate. The
      calibration techniques attempt to adaptively recover the biothermal
      heterogeneities within the tissue on a patient-specific level and results in a
      formidable PDE constrained optimization problem to be solved in real time. A
      comprehensive calibration study is performed with both homogeneous and spatially
      heterogeneous biothermal model parameters with and without constitutive
      nonlinearities. Initial results presented here indicate that the calibration
      problems involving the inverse solution of thousands of model parameters can
      converge to a solution within three minutes and decrease the [see text for
      symbol](L) (2) (2) ((0, T; L) (2) ((Omega))) norm of the difference between
      computational prediction and the measured temperature values to a patient
      specific regime.

PMID- 20142154
TI  - Laser reflectance imaging of human chest for localization of internal organs.
AB  - The normalized backscattered intensity (NBI) profiles at various locations of
      human thorax by multiprobe laser reflectometer are obtained. These data after
      digitization, interpolation, and filtering are color-coded and displayed as
      images on the outline of the human thorax. For optical characterization of
      tissues in terms of their parameters, scattering and absorption coefficients and
      the anisotropy parameter (g) are obtained by matching the measured NBI profile
      with that as obtained by Monte Carlo simulation procedure. Corresponding to the
      variation of the NBI over the various regions, the optical parameters show their
      respective changes. The maximum absorption and minimum scattering coefficients
      are observed at the areola, clavicle, sternum, scapula, and vertebral column. The
      minimum absorption and maximum scattering coefficients are observed at the
      pectoralis major of chest and rectus abdominis of abdomen regions, as compared to
      the other regions, attributed to their tissue compositional variations. To
      visualize the various tissues in lower regions of the thorax, the color-coded
      scheme of the NBI variation, as measured by the third fiber, is further expanded.
      By this procedure, the outlines of the heart and lungs, as detected through
      intercostals regions, are observed, which is in good agreement with that as
      determined by the chest radiograph of the same subject taken in PA position.
      Similarly the lower sections of the liver and stomach, due to their distinct
      optical parameters, are also observed.

PMID- 20142155
TI  - Wavelet-based ECG data compression system with linear quality control scheme.
AB  - Maintaining reconstructed signals at a desired level of quality is crucial for
      lossy ECG data compression. Wavelet-based approaches using a recursive
      decomposition process are unsuitable for real-time ECG signal recoding and
      commonly obtain a nonlinear compression performance with distortion sensitive to
      quantization error. The sensitive response is caused without compromising the
      influences of word-length-growth (WLG) effect and unfavorable for the
      reconstruction quality control of ECG data compression. In this paper, the 1-D
      reversible round-off nonrecursive discrete periodic wavelet transform is applied
      to overcome the WLG magnification effect in terms of the mechanisms of error
      propagation resistance and significant normalization of octave coefficients. The
      two mechanisms enable the design of a multivariable quantization scheme that can
      obtain a compression performance with the approximate characteristics of linear
      distortion. The quantization scheme can be controlled with a single control
      variable. Based on the linear compression performance, a linear quantization
      scale prediction model is presented for guaranteeing reconstruction quality.
      Following the use of the MIT-BIH arrhythmia database, the experimental results
      show that the proposed system, with lower computational complexity, can obtain
      much better reconstruction quality control than other wavelet-based methods.

PMID- 20142156
TI  - Using increased structural detail of the cortex to improve the accuracy of
      modeling the effects of transcranial magnetic stimulation on neocortical
      activation.
AB  - Transcranial magnetic stimulation (TMS) is a noninvasive technique that can alter
      brain activation by inducing electrical current in neurons using dynamic magnetic
      fields. Because of its painless nature, clinical usage has expanded to diagnostic
      purposes and therapeutic treatments. However, several issues and challenges still
      exist for TMS. A very limited understanding of the interaction between magnetic
      fields, cortical structure, and consequent brain excitation is currently
      available. Most previously published models lack key anatomical details that are
      essential elements in calculating induced electric fields critical to brain
      activation. In this study, gross human brain and head structures were derived
      using multiple modality images and a finite-element model was constructed.
      Furthermore, microstructural detail was incorporated using neocortical columnar
      structures. Using this detailed model, we investigated the influence of TMS coil
      position, distance and orientation on induced electric fields, and neocortical
      activation. Several activation standards and conductivity values were tested for
      their impact on the distribution of neocortical activation. Optimized activation
      patterns agreed well with published clinical experiments, under similar coil
      configurations. A structurally detailed finite-element model capable of
      accurately predicting neocortical activation for a given coil/magnetic field
      profile may provide a critical resource for understanding the
      electrophysiological consequences of TMS and for further refinement of this
      important technique.

PMID- 20142157
TI  - A principal component regression approach for estimation of ventricular
      repolarization characteristics.
AB  - The time interval between Q-wave onset and T-wave offset, i.e., QT interval, in
      an ECG corresponds to the total ventricular activity, including both
      depolarization and repolarization times. It has been suggested that abnormal QT
      variability could be a marker of cardiac diseases such as ventricular
      arrhythmias, and QT-interval has also been observed to lengthen during
      hypoglycemia. In this paper, we propose a robust method for estimating
      ventricular repolarization characteristics such as QT interval and T-wave
      amplitude. The method is based on principal component regression. In the method,
      QT epochs are first extracted from ECG in respect of R-waves. Then, correlation
      matrix of the extracted epochs is formed and its eigenvectors computed. The most
      significant eigenvectors are then fitted to the data to obtain noise-free
      estimates of QT epochs. Nonstationarities in QT-epoch characteristics can also be
      modeled by updating the eigenvectors dynamically. The main benefit of the
      proposed method is robustness to noise, i.e., it works also when using ECGs that
      have low SNR, for example, signals measured during normal-life environments. One
      application of the proposed method could be the detection of the hypoglycemia.

PMID- 20142158
TI  - Discrete deformable model guided by partial active shape model for TRUS image
      segmentation.
AB  - Automatic prostate segmentation in transrectal ultrasound (TRUS) images is highly
      desired in many clinical applications. However, robust and automated prostate
      segmentation is challenging due to the low SNR in TRUS and the missing boundaries
      in shadow areas caused by calcifications or hyperdense prostate tissues. This
      paper presents a novel method of utilizing a priori shapes estimated from partial
      contours for segmenting the prostate. The proposed method is able to
      automatically extract prostate boundary from 2-D TRUS images without user
      interaction for shape correction in shadow areas. During the segmentation
      process, missing boundaries in shadow areas are estimated by using a partial
      active shape model, which takes partial contours as input but returns a complete
      shape estimation. With this shape guidance, an optimal search is performed by a
      discrete deformable model to minimize an energy functional for image
      segmentation, which is achieved efficiently by using dynamic programming. The
      segmentation of an image is executed in a multiresolution fashion from coarse to
      fine for robustness and computational efficiency. Promising segmentation results
      were demonstrated on 301 TRUS images grabbed from 19 patients with the average
      mean absolute distance error of 2.01 mm +/- 1.02 mm.

PMID- 20142159
TI  - High resolution cerebral blood flow imaging by registered laser speckle contrast
      analysis.
AB  - Laser speckle imaging (LSI) has been widely used for in vivo detecting cerebral
      blood flow (CBF) under various physiological and pathological conditions. So far,
      nearly all literature on in vivo LSI does not consider the influence of
      disturbances due to respiration and/or heart beating of animals. In this paper,
      we analyze how such physiologic motions affect the spatial resolution of the
      conventional laser speckle contrast analysis (LASCA). We propose a registered
      laser speckle contrast analysis (rLASCA) method which first registers raw speckle
      images with a 3 x 3 convolution kernel, normalized correlation metric and cubic B
      spline interpolator, and then constructs the contrast image for CBF. rLASCA not
      only significantly improves the distinguishability of small vessels, but also
      efficiently suppresses the noises induced by respiration and/or heart beating. In
      an application of imaging the angiogenesis of rat's brain tumor, rLASCA
      outperformed the conventional LASCA in providing a much higher resolution for new
      small vessels. As a processing method for LSI, rLASCA can be directly applied to
      other LSI experiments where the disturbances from different sources (like
      respiration, heart beating) exist.

PMID- 20142160
TI  - Propofol effects on atrial fibrillation wavefront delays.
AB  - Since the cardiac activity during atrial fibrillation (AF) may be influenced by
      autonomic modulations, in this study, a novel method to quantify the effects of
      the most common anesthetic agent (propofol) in AF ablation procedures is
      introduced. This study has two main objectives: first, to assess whether the
      sedation earlier to radio frequency ablation affects the arrhythmia itself, and
      second, to provide new information that contributes to a better understanding of
      the influence of the autonomic nervous system on AF. The methodology presented is
      based on the measurement of synchronization and delay indexes between two atrial
      activations at adjacent intracavitary electrodes. These parameters aim to
      estimate whether two activations at different sites may be caused by the same
      propagating wavefront, or otherwise, are the consequence of independent
      wavefronts. The results showed that the mentioned indexes have a different
      behavior at both atria: the right atrium becomes more synchronized with propofol
      administration, whereas the synchronization index decreases at the left atrium.

PMID- 20142161
TI  - Automatic detection of scoliotic curves in posteroanterior radiographs.
AB  - Spinal deformities are diagnosed using posteroanterior (PA) radiographs.
      Automatic detection of the spine on conventional radiographs would be of interest
      to quantify curve severity, would help reduce observer variability and would
      allow large-scale retrospective studies on radiographic databases. The goal of
      this paper is to present a new method for automatic detection of spinal curves
      from a PA radiograph. A region of interest (ROI) is first extracted according to
      the 2-D shape variability of the spine obtained from a set of PA radiographs of
      scoliotic patients. This region includes 17 bounding boxes delimiting each
      vertebral level from T1 to L5. An adaptive filter combining shock with complex
      diffusion is used to individually restore the image of each vertebral level.
      Then, texture descriptors of small block elements are computed and submitted for
      training to support vector machines (SVM). Vertebral body's locations are thereby
      inferred for a particular vertebral level. The classifications of block elements
      for all 17 SVMs are identified in the image and a voting system is introduced to
      cumulate correctly predicted blocks. A spline curve is then fitted through the
      centers of the predicted vertebral regions and compared to a manual
      identification using a Student t-test. A clinical validation is performed using
      100 radiographs of scoliotic patients (not used for training) and the detected
      spinal curve is found to be statistically similar (p < 0.05) in 93% of cases to
      the manually identified curve.

PMID- 20142162
TI  - An integrated port camera and display system for laparoscopy.
AB  - In this paper, we built and tested the port camera, a novel, inexpensive,
      portable, and battery-powered laparoscopic tool that integrates the components of
      a vision system with a cannula port. This new device 1) minimizes the
      invasiveness of laparoscopic surgery by combining a camera port and tool port; 2)
      reduces the cost of laparoscopic vision systems by integrating an inexpensive
      CMOS sensor and LED light source; and 3) enhances laparoscopic surgical
      procedures by mechanically coupling the camera, tool port, and liquid crystal
      display (LCD) screen to provide an on-patient visual display. The port camera
      video system was compared to two laparoscopic video systems: a standard
      resolution unit from Karl Storz (model 22220130) and a high definition unit from
      Stryker (model 1188HD). Brightness, contrast, hue, colorfulness, and sharpness
      were compared. The port camera video is superior to the Storz scope and
      approximately equivalent to the Stryker scope. An ex vivo study was conducted to
      measure the operative performance of the port camera. The results suggest that
      simulated tissue identification and biopsy acquisition with the port camera is as
      efficient as with a traditional laparoscopic system. The port camera was
      successfully used by a laparoscopic surgeon for exploratory surgery and liver
      biopsy during a porcine surgery, demonstrating initial surgical feasibility.

PMID- 20142163
TI  - Graph-based variability estimation in single-trial event-related neural
      responses.
AB  - Extracting information from multitrial magnetoencephalography or
      electroencephalography (EEG) recordings is challenging because of the very low
      SNR, and because of the inherent variability of brain responses. The problem of
      low SNR is commonly tackled by averaging multiple repetitions of the recordings,
      also called trials, but the variability of response across trials leads to biased
      results and limits interpretability. This paper proposes to decode the
      variability of neural responses by making use of graph representations. Our
      approach has several advantages compared to other existing methods that process
      single-trial data: first, it avoids the a priori definition of a model for the
      waveform of the neural response; second, it does not make use of the average data
      for parameter estimation; third, it does not suffer from initialization problems
      by providing solutions that are global optimum of cost functions; and last, it is
      fast. We proceed in two steps. First, a manifold learning algorithm, based on a
      graph Laplacian, offers an efficient way of ordering trials with respect to the
      response variability, under the condition that this variability itself depends on
      a single parameter. Second, the estimation of the variability is formulated as a
      combinatorial optimization that can be solved very efficiently using graph cuts.
      Details and validation of this second step are provided for latency estimation.
      Performance and robustness experiments are conducted on synthetic data, and
      results are presented on EEG data from a P300 oddball experiment.

PMID- 20142164
TI  - Wavelet phase synchronization analysis of cerebral blood flow autoregulation.
AB  - The dynamic relationship between beat-to-beat mean arterial blood pressure (ABP)
      fluctuations and cerebral blood flow velocity (CBFV) variations have been
      intensively studied. The experimentally observed low coherence in the low
      frequency band has previously indicated that the assumptions of linearity and/or
      stationarity, the preconditions of the linear transfer function analysis, are not
      valid in that frequency region. Latka et al. [M. Latka, M. Turalska, M. Glaubic
      Latka, W. Kolodziej, D. Latka, and B. J. J. West, "Phase dynamics in cerebral
      autoregulation," Amer. J. Physiol. Heart Circ. Physiol., vol. 289 pp. H2272
      H2279, Jul. 2005] used a wavelet phase synchronization method to identify the
      instantaneous phase difference between ABP and CBFV, and low values of
      synchronization index were found in the low-frequency range, seeming to provide
      further evidence that the cerebral autoregulation system is nonstationary. Here,
      we focus on another possible factor corresponding for this low synchronization
      index-unmeasured variability. We demonstrate analytically and with a
      physiologically based cerebral hemodynamic model that, in the case of multiple
      inputs, the phase difference between one input, ABP, and the output, CBFV, will
      be distorted by an additional input, end-tidal CO(2) (P(ETCO(2))), and no longer
      accurately represent the true ABP-CBFV system phase shift. We also prove that
      this phase distortion can be corrected if the transfer functions for ABP-CBFV and
      P(ETCO(2))-CBFV are known or can be estimated. A significantly increased value of
      synchronization index in the low-frequency band is found by using the CO(2)
      correction term with experimental data on 13 subjects. This essentially indicates
      that the lack of synchronization between ABP and CBFV previously identified by
      Latka et al. [M. Latka, M. Turalska, M. Glaubic-Latka, W. Kolodziej, D. Latka,
      and B. J. J. West, "Phase dynamics in cerebral autoregulation," Amer. J. Physiol.
      Heart Circ. Physiol., vol. 289, pp. H2272-H2279, Jul. 2005] can be partly
      attributed to unmeasured variability.

PMID- 20142165
TI  - Foundations of implementing the competitive layer model by Lotka-Volterra
      recurrent neural networks.
AB  - The competitive layer model (CLM) can be described by an optimization problem.
      The problem can be further formulated by an energy function, called the CLM
      energy function, in the subspace of nonnegative orthant. The set of minimum
      points of the CLM energy function forms the set of solutions of the CLM problem.
      Solving the CLM problem means to find out such solutions. Recurrent neural
      networks (RNNs) can be used to implement the CLM to solve the CLM problem. The
      key point is to make the set of minimum points of the CLM energy function just
      correspond to the set of stable attractors of the recurrent neural networks. This
      paper proposes to use Lotka-Volterra RNNs (LV RNNs) to implement the CLM. The
      contribution of this paper is to establish foundations of implementing the CLM by
      LV RNNs. The contribution mainly contains three parts. The first part is on the
      CLM energy function. Necessary and sufficient conditions for minimum points of
      the CLM energy function are established by detailed study. The second part is on
      the convergence of the proposed model of the LV RNNs. It is proven that
      interesting trajectories are convergent. The third part is the most important. It
      proves that the set of stable attractors of the proposed LV RNN just equals the
      set of minimum points of the CLM energy function in the nonnegative orthant.
      Thus, the LV RNNs can be used to solve the problem of the CLM. It is believed
      that by establishing such basic rigorous theories, more and interesting
      applications of the CLM can be found.

PMID- 20142166
TI  - Coarse-to-fine boundary location with a SOM-like method.
AB  - A coarse-to-fine boundary location with a self-organizing map (SOM)-like method
      is proposed in this paper. Inspired from the conventional SOM and universal
      gravitation, given a small quantity of supervision seeds from the desired
      boundaries, neurons are used to evolve to the desired boundaries in a coarse-to
      fine framework. The major components of this framework are the designs of union
      action and evolving rate. In the course of neuron evolution, the union actions
      acting on these neurons will offer them the evolving directions. Also controlled
      by the corresponding referenced gradients, the neurons' evolving rates are
      adaptively adjusted at different positions. With the union actions and evolving
      rates, the neurons will evolve with appropriate manners to expand the set of
      feature points on the desired boundaries. The newly expanded feature points will
      cause the generation updates for feature points and neurons, and offer new
      information to guide the new generation of neurons to the boundaries. What is
      more, the proposed multiround evolution is as well a coarse-to-fine way for
      boundary location. Experiments and comparisons show that the proposed method
      performs well in complex long concavities, inhomogeneous and weak boundary
      location with good initialization flexibility.

PMID- 20142167
TI  - Climate variability and hemorrhagic fever with renal syndrome transmission in
      Northeastern China.
AB  - BACKGROUND: The transmission of hemorrhagic fever with renal syndrome (HFRS) is
      influenced by climatic variables. However, few studies have examined the
      quantitative relationship between climate variation and HFRS transmission.
      OBJECTIVE: We examined the potential impact of climate variability on HFRS
      transmission and developed climate-based forecasting models for HFRS in
      northeastern China. METHODS: We obtained data on monthly counts of reported HFRS
      cases in Elunchun and Molidawahaner counties for 1997-2007 from the Inner
      Mongolia Center for Disease Control and Prevention and climate data from the
      Chinese Bureau of Meteorology. Cross-correlations assessed crude associations
      between climate variables, including rainfall, land surface temperature (LST),
      relative humidity (RH), and the multivariate El Nino Southern Oscillation (ENSO)
      index (MEI) and monthly HFRS cases over a range of lags. We used time-series
      Poisson regression models to examine the independent contribution of climatic
      variables to HFRS transmission. RESULTS: Cross-correlation analyses showed that
      rainfall, LST, RH, and MEI were significantly associated with monthly HFRS cases
      with lags of 3-5 months in both study areas. The results of Poisson regression
      indicated that after controlling for the autocorrelation, seasonality, and long
      term trend, rainfall, LST, RH, and MEI with lags of 3-5 months were associated
      with HFRS in both study areas. The final model had good accuracy in forecasting
      the occurrence of HFRS. CONCLUSIONS: Climate variability plays a significant role
      in HFRS transmission in northeastern China. The model developed in this study has
      implications for HFRS control and prevention.

PMID- 20142168
TI  - Reflections on that "City by the Bay"; a smaller world for better patient care.

PMID- 20142169
TI  - "Old" problems revisited; imaging the coronary in high resolution.

PMID- 20142170
TI  - Transferability of data between different drug-eluting stents.

PMID- 20142171
TI  - PCR and Singapore LIVE join forces: 1+1>3.

PMID- 20142172
TI  - Interventional cardiologists: a new breed?

PMID- 20142173
TI  - Comparison of optical coherence tomography and intravascular ultrasound for the
      assessment of in-stent tissue coverage after stent implantation.
AB  - AIMS: At present there exists no direct comparative data for the detection of in
      stent tissue coverage as assessed by intravascular ultrasound (IVUS) and optical
      coherence tomography (OCT) in clinical settings. To explore this subject, we
      investigated the correlation between the IVUS and OCT measurements derived from a
      contemporary population. METHODS AND RESULTS: The present study includes 20
      patients who had stents imaged at a six months follow-up with both IVUS and OCT,
      acquired with an automated pull-back. Off-line analyses were done by an
      independent validated Core-Lab (RHR, Rome, Italy). Measurements of stent length
      obtained by IVUS and OCT were 16.3+/-3.0 mm and 16.2+/-3.8 mm respectively
      (p=0.82) and were similar to nominal length (16.3+/-3.3 mm). Luminal area in the
      OCT image set was lower than that obtained in the corresponding IVUS image set
      (3.83+/-1.60 mm2 vs 4.05+/-1.44 mm2, p<0.001), while stent area was significantly
      higher when measured by OCT (6.61+/-1.39 mm2 vs 6.17+/-1.07 mm2, p<0.001). The
      percentage of tissue coverage measured by IVUS was lower than that measured in
      the corresponding OCT image sets (35.5+/-16.4% vs 43.4+/-16.1%, p<0.001).
      Correlation coefficients were high for repeated OCT measurements by two different
      observers (r=0.99). CONCLUSIONS: OCT can quantify in-stent coverage and detect
      strut healing with high reproducibility. IVUS tends to underestimate the
      percentage of in-stent tissue coverage as compared to OCT.

PMID- 20142174
TI  - Optical coherence tomography assessment of a new dedicated bifurcation stent.
AB  - AIMS: Dedicated bifurcation stents should facilitate deployment and improve
      coverage of bifurcational lesions. We used optical coherence tomography (OCT) to
      assess bifurcation lesions treated with a dedicated stent implanted in the side
      branch (SB) in conjunction with drug eluting stents in the main vessel (MV) in a
      culotte-like fashion. METHODS AND RESULTS: Nine patients treated with the Tryton
      stent underwent postprocedural OCT examination. Total percent of malapposed
      struts per patient was 18.1+/-8.7%. The longitudinal distribution of the percent
      of malapposed struts per patient showed that the prevalence of malapposed struts
      was significantly higher at the level of the bifurcation (33.3%), than in both
      the proximal segment and the distal segment (18.5% and 9.8%, respectively,
      p=0.011). When the bifurcation was divided into two halves (opposite SB and
      toward SB), the highest percent of malapposed struts was toward the SB (47.6%).
      Also the wall-strut distance for malapposed struts was significantly higher in
      the bifurcation half toward the SB than in the proximal and the distal segment.
      CONCLUSIONS: Malapposed struts are frequent in bifurcations despite the use of a
      dedicated stent. The highest frequency and largest vessel wall-stent strut
      distance are observed in the bifurcation half toward the SB.

PMID- 20142175
TI  - First-in-man (FIM) experience with the Magnetic Medical Positioning System (MPS)
      for intracoronary navigation.
AB  - AIMS: To investigate the safety and feasibility of a newly developed magnetic
      navigation system for intracoronary tracking. METHODS AND RESULTS: The MediGuide
      Medical Positioning System (MPS) is a navigation system that was developed to
      facilitate the navigation of enabled devices within the coronary tree using a
      magnetic tracking technology. The current prospective, non-randomised, single
      centre, first-in-man study was conducted at Universitatsklinikum Regensburg
      (UKR), Germany on an MPS-enabled AXIOM Artis dFC coronary angiography system
      (Siemens AG, Forchheim, Germany). We enrolled 20 patients who required IVUS
      assessment or treatment of a single de novo target lesion in a native coronary
      artery. The performance was evaluated on a semi-quantitative one-to-five scale
      where a score of five indicates an excellent superimposition with the vessel and
      a score of one an unacceptable performance. The mean score for tracking as
      assessed by projection on life fluoroscopy was 4.89 and 3.58 as assessed by
      projection on recorded cine-loop. Length measurement of a 20 mm distance was
      significantly better with the MPS (mean deviation of 0.6 mm=3%) as compared to
      standard QCA (1.5 mm=8%, p<0.05). Creating a 3D reconstruction was possible in 13
      out of 20 cases with an average score of 4.68. No adverse events occurred.
      CONCLUSIONS: The MediGuide Medical Positioning System is safe and feasible in
      man, facilitates intracoronary navigation and allows 3D reconstruction of the
      investigated coronary segment.

PMID- 20142176
TI  - Compositional volumetry of non-calcified coronary plaques by multislice computed
      tomography: an ex vivo feasibility study.
AB  - AIMS: Non-invasive quantitative compositional analysis of coronary plaque would
      be a major advantage to study coronary artery disease. This study explores the
      application to use the Hounsfield units (HU) distribution of coronary plaques
      imaged by multislice computed tomography-coronary angiography (MSCT-CA). METHODS
      AND RESULTS: A dedicated computer-assisted method was developed to measure the HU
      distribution within a coronary plaque by MSCT-CA. To test the feasibility of the
      method, an ex vivo left anterior descending (LAD) coronary specimen, excised
      during autopsy, was imaged both by non-enhanced and enhanced MSCT-CA.
      Quantitative histology was used as a reference. To test the feasibility of the
      new volumetric analytic method, the MSCT-CA data were compared with volumetric
      histopathology. The coronary specimen, with a heterogeneously distributed plaque
      composition without large areas of calcification, was histologically sampled at
      five different locations, 5 mm apart, where at each location 15 sections were
      taken at 100 microm intervals, resulting in 75 individual histology sections. Tri
      chrome Masson staining was used for histology quantification of three
      plaque/tissue components: smooth muscle cells (SMC), collagen and calcium. MSCT
      plaque composition was defined as "lower-HU" or "higher-HU" plaque and "calcium"
      based on the HU distribution. Comparison of the MSCT defined tissue components
      against histology showed a good relationship without significant differences.
      CONCLUSIONS: This ex vivo study shows the feasibility of using the Hounsfield
      unit distribution to perform compositional coronary plaque volumetry by MSCT-CA.
      The results are encouraging.

PMID- 20142177
TI  - Impact of sirolimus-eluting stent implantation compared to bare-metal stent
      implantation for acute myocardial infarction on coronary plaque composition at
      nine months follow-up: a Virtual Histology intravascular ultrasound analysis.
      Results from the Leiden MISSION! intervention study.
AB  - AIMS: To evaluate effects of sirolimus-eluting stents (SES) compared to bare
      metal stents (BMS) at stent edges in patients with acute myocardial infarction
      (AMI). METHODS AND RESULTS: Clinical, angiographic, intravascular ultrasound
      (lVUS) and virtual histology (VH)-IVUS results were obtained and analysed in 20
      SES and 20 BMS AMI patients at the index procedure and at nine months follow-up.
      Quantitative angiography and IVUS showed a trend toward decreases in mean lumen
      diameter, vessel volume, minimum lumen area and mean lumen area at both stent
      edges of BMS, and at the proximal edge of SES. At the distal stent edge, a
      significant difference between BMS and SES treated patients in mean lumen area
      was found (D-0.8+/-1.6 mm2 versus D0.2+/-0.8 mm2 respectively, p=0.04).
      Furthermore, in-stent SES had a larger lumen volume (SES: 167.7+/-59.2 mm3 versus
      BMS: 125.1+/-43.8 mm3; p=0.02) and less neointima volume (7.3+/-9.1 mm3 versus
      53.2+/-35.1 mm3; p<0.001). Neither SES nor BMS demonstrated a significant effect
      on plaque composition at follow-up VH-IVUS analysis. CONCLUSIONS: A significant
      difference between SES and BMS treated patients was observed with respect to mean
      lumen diameter distal to the stented segment which suggests a downstream effect
      of sirolimus elution.

PMID- 20142178
TI  - Determination of haemodynamic significance of intermediate coronary lesions using
      three-dimensional coronary reconstruction.
AB  - AIMS: This study evaluates three-dimensional (3-D) reconstruction of the coronary
      arteries in assessment of angiographically borderline lesions. METHODS AND
      RESULTS: Three-dimensional (3-D) quantitative coronary angiography (QCA) was
      performed for 41 intermediate coronary stenotic lesions (IL) in 31 patients.
      Measurements of cross-sectional stenosis (CSS), diameter stenosis (DS) and plaque
      volume (PV) were correlated with the fractional flow reserve (FFR) values
      measured with a commercially-available pressure guide-wire. FFR <0.75 was
      considered significant. Using FFR, only 9/41 lesions appeared haemodynamically
      significant (FFR <0.75). When compared to lesions with an FFR >0.75, these
      lesions had higher CSS (65.3+/-9.4% vs. 44.7+/-10.6%, p=0.0001), higher DS (48+/
      5.7% vs. 32.5+/-9.9%, p=0.0001), and higher PV (41.6+/-7.6% vs. 29.4+/-6.7%,
      p=0.0005), as measured by 3-D QCA. Regression analysis showed significant
      correlations between FFR and CSS (r=-0.481, p=0.001) and PV (r=-0.443, p=0.004),
      and a modest correlation between FFR and DS (r=-0,320, p=0.041). Compared with
      FFR, a CSS of 57% had the highest sensitivity and specificity (88.9% and 87.5%,
      respectively) for determining significant IL. Multivariate analysis showed 3-D
      determined CSS to better predict FFR compared to the other measured variables
      (p=0.012). CONCLUSIONS: Parameters obtained by 3-D QCA showed a significant
      correlation with FFR values. A cross-sectional stenosis >57% obtained by 3-D QCA
      has a high degree of sensitivity and specificity to detect a haemodynamically
      significant intermediate coronary stenosis.

PMID- 20142179
TI  - A comparison of patient characteristics and 30-day mortality outcomes after
      transcatheter aortic valve implantation and surgical aortic valve replacement for
      the treatment of aortic stenosis: a two-centre study.
AB  - AIMS: It is unclear whether transcatheter aortic valve implantation (TAVI)
      addresses an unmet clinical need for those currently rejected for surgical aortic
      valve replacement (SAVR) and whether there is a subgroup of high-risk patients
      benefiting more from TAVI compared to SAVR. In this two-centre, prospective
      cohort study, we compared baseline characteristics and 30-day mortality between
      TAVI and SAVR in consecutive patients undergoing invasive treatment for aortic
      stenosis. METHODS AND RESULTS: We pre-specified different adjustment methods to
      examine the effect of TAVI as compared with SAVR on overall 30-day mortality:
      crude univariable logistic regression analysis, multivariable analysis adjusted
      for baseline characteristics, analysis adjusted for propensity scores, propensity
      score matched analysis, and weighted analysis using the inverse probability of
      treatment (IPT) as weights. A total of 1,122 patients were included in the study:
      114 undergoing TAVI and 1,008 patients undergoing SAVR. The crude mortality rate
      was greater in the TAVI group (9.6% vs. 2.3%) yielding an odds ratio [OR] of 4.57
      (95%-CI 2.17-9.65). Compared to patients undergoing SAVR, patients with TAVI were
      older, more likely to be in NYHA class III and IV, and had a considerably higher
      logistic EuroSCORE and more comorbid conditions. Adjusted OR depended on the
      method used to control for confounding and ranged from 0.60 (0.11-3.36) to 7.57
      (0.91-63.0). We examined the distribution of propensity scores and found scores
      to overlap sufficiently only in a narrow range. In patients with sufficient
      overlap of propensity scores, adjusted OR ranged from 0.35 (0.04-2.72) to 3.17
      (0.31 to 31.9). In patients with insufficient overlap, we consistently found
      increased odds of death associated with TAVI compared with SAVR irrespective of
      the method used to control confounding, with adjusted OR ranging from 5.88 (0.67
      51.8) to 25.7 (0.88-750). Approximately one third of patients undergoing TAVI
      were found to be potentially eligible for a randomised comparison of TAVI versus
      SAVR. CONCLUSIONS: Both measured and unmeasured confounding limit the conclusions
      that can be drawn from observational comparisons of TAVI versus SAVR. Our study
      indicates that TAVI could be associated with either substantial benefits or
      harms. Randomised comparisons of TAVI versus SAVR are warranted.

PMID- 20142180
TI  - Safety, efficacy and long-term durability of endovascular therapy for carotid
      artery disease: the tailored-Carotid Artery Stenting Experience of a single high
      volume centre (tailored-CASE Registry).
AB  - AIMS: We aimed to determine the success, safety and long-term durability of
      carotid artery stenting (CAS) in stroke prevention for all-comers managed with
      mandatory neuroprotection and a tailored-approach to intervention. METHODS AND
      RESULTS: From our CAS registry (beginning July 1997) all procedures up to
      September 2007 with intention-to-treat by stenting under distal filter or
      proximal occlusion neuroprotection devices were analysed (N=1523; mean age 72
      years [237 >or=80 years, 15.5%]). Indications included symptomatic stenoses
      >or=50% (366, 24.1%) and asymptomatic stenoses >or=80% (1157, 75.9%). CAS success
      was 99.6% and the 30-day all-stroke/death rate was 1.5% (minor stroke 11 [0.7%],
      major stroke 8 [0.5%], death 5 [0.3%]). The risk was 1.2% for asymptomatic
      patients and 2.7% for symptomatic patients (p=0.042). Regarding octogenarians
      this risk was 2.1% versus 1.5% for patients <or=79 years (p=0.47). Symptomatic
      octogenarians had a higher risk than other groups (OR 3.9, 95% CI 1.06 to 14.0):
      asymptomatic <or=79 1.2%, asymptomatic >or=80 1.2%, symptomatic <or=79 2.3% and
      symptomatic >or=80 4.5%. The event free survival rates from all strokes or stroke
      related deaths at eight years were 96% for asymptomatic and 92% for symptomatic
      patients. CONCLUSIONS: Results from this large cohort show that carotid stenting
      in a real-world setting is safe and efficacious, and durable in the long-term
      prevention of stroke.

PMID- 20142181
TI  - The safety and feasibility of immediately returning patients transferred for
      primary percutaneous coronary intervention with ST-elevation myocardial
      infarction.
AB  - AIMS: To describe the safety of immediate retransfer to community hospitals
      following primary percutaneous coronary intervention (PCI) for ST-elevation
      myocardial infarction (STEMI). METHODS AND RESULTS: In a cohort of 246
      consecutive patients transferred to a tertiary institution who all underwent
      primary or rescue PCI, 166 (67%) were immediately retransferred back. The
      retransfer occurred only if they were haemodynamically stable and had undergone
      an uncomplicated procedure. In-hospital adverse events were assessed in each
      referral hospital. Patients had a mean age of 59 years, presented an anterior MI
      in 39%, and 91% were in Killip class 1. In this cohort, 75% of patients underwent
      primary PCI and 25% received rescue PCI. A transradial approach was used in 74%
      of patients. During ambulance transport back to the referral hospital, no adverse
      events occurred. In-hospital outcomes were favourable, with low death (2.4%),
      reinfarction (3.6%) and stroke (1.2%) rates. TIMI major bleeding occurred in 1.8%
      (catheter-related in 0.6%). CONCLUSIONS: In this carefully selected population of
      STEMI patients, immediate retransfer to the referral hospital following primary
      or rescue PCI is feasible in more than 2/3 of patients and associated with a low
      risk of major clinical adverse events.

PMID- 20142182
TI  - Impact of platelet glycoprotein IIb/IIIa receptor inhibitors on renal function in
      patients with ST-segment elevation myocardial infarction treated with primary or
      rescue percutaneous coronary intervention.
AB  - AIMS: Worsening renal function in patients undergoing percutaneous coronary
      intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated
      with adverse clinical outcomes. We hypothesised that platelet glycoprotein
      IIb/IIIa receptor inhibitors (GPI) may decrease the rate of renal function
      deterioration in these patients through attenuation of platelet aggregation and
      the possible improvement of renal rheology and haemodynamics. METHODS AND
      RESULTS: Based on prospectively collected data, we analysed rates of renal
      function deterioration in 603 consecutive patients (mean age 58+/-13 years, males
      82%) with STEMI treated with primary or rescue PCI. Renal function deterioration
      was defined as an increase in serum creatinine level of >or=25% and/or >or=0.5
      mg/dl at any time point post-PCI during index hospitalisation compared with
      baseline value. Outcomes were stratified by treatment with GPI. Patients treated
      with GPI (n=442) vs. patients who were not treated with GPI (n=161) had
      significantly lower rates of serum creatinine increase of >or=25% compared with
      baseline (22.9% vs. 31.9%, P=0.02, respectively), of serum creatinine increase
      >or=0.5 g/dL (4.1% vs. 8.8%, P=0.02). Treatment with GPI was associated with
      significantly lower mean maximal increase in serum creatinine level compared with
      baseline value (0.14+/-0.38 vs. 0.25+/-0.45 mg/dL, P=0.005). Rates of major
      bleeding did not differ significantly between the two groups (7.3% vs. 5.9%;
      P=0.42), while 30-day mortality was significantly lower in patients treated with
      GPI (2.3% vs. 7.5%; P=0.005). By multivariable analysis, treatment with GPI was
      an independent predictor of freedom from renal function deterioration (odds ratio
      0.53; 95% confidence interval 0.33-0.86; P=0.01). CONCLUSIONS: In this analysis,
      administration of GPI to patients with STEMI treated with primary PCI was
      associated with lower rates of worsening renal function and lower 30-day
      mortality.

PMID- 20142184
TI  - A third generation ultra-thin strut cobalt chromium stent: histopathological
      evaluation in porcine coronary arteries.
AB  - AIMS: The present study was designed to evaluate a novel third generation bare
      metal stent (BMS) comprised of an ultra-thin-strut, cobalt-chromium platform with
      fixed geometry, uniform cell size, and superior surface finish in a porcine
      coronary artery model. METHODS AND RESULTS: A total of 47 BMS of two types were
      implanted in pig coronary arteries using QCA to optimise stent apposition: a
      commercially available cobalt alloy thin-strut stent (91 microm) as control
      (Driver; n=17), and an ultra-thin-strut (65 microm) cobalt-chromium stent
      (Protea; n=18). Animals underwent angiographic restudy and termination one week
      and one month post-implant for coronary artery histology. In addition, 12
      overlapping Protea stents were analysed at one month. At one week, comparable
      thin neointima and mild inflammation were observed in both groups. At one month,
      Protea demonstrated significantly lower angiographic % stenosis (2+/-1% vs. 17+/
      5%, p=0.006), intimal thickness (0.11+/-0.01 mm vs. 0.23+/-0.03 mm, p=0.003), and
      histologic % area stenosis (19+/-2% vs. 32+/-3%, p=0.003). Mean stent strut
      injury scores were low and similar between groups. Angiographic % stenosis,
      intimal thickness, and histologic % area stenosis of overlapping Protea stents
      were 3+/-1%, 0.13+/-0.01 mm, and 22+/-2%, respectively, and similar to the single
      Protea group. Stable fibrocellular neointimal incorporation, with complete
      endothelialisation and minimal inflammation, were observed at one month in all
      stents, including overlapped Protea segments. CONCLUSIONS: When compared to a
      commercially available cobalt alloy BMS, the new third generation Protea stent
      demonstrated favourable coronary arterial response with significant reduction of
      neointimal formation in the porcine model. Our results showed how seemingly
      trivial improvements to the BMS technology can result in substantial biological
      responses. Future, long-term investigations are needed to ascertain the clinical
      applicability and implications of these findings.

PMID- 20142185
TI  - How should I treat a complex Post-CABG patient?
AB  - BACKGROUND: A 69 year old man was admitted with unstable angina (Class IIB). He
      had a history of chronic renal impairment, diabetes mellitus, hypertension and
      coronary bypass surgery in 1997 (LIMA graft to the LAD anf diagonal branch,
      saphenous vein grafts to the RCA and first marginal branch of LCx. INVESTIGATION:
      Coronary angiography. DIAGNOSIS: Unstable angina (Class IIB). Occlusion of the
      LCx and RCA. Functionally occluded LIMA on the LAD and diagonal branch. Diffuse
      disease of the LAD with two significant lesions at the LAD-first diagonal and mid
      distal LAD. TREATMENT: Revascularisation.

PMID- 20142183
TI  - Causes of death in early MI survivors with persistent infarct artery occlusion:
      results from the Occluded Artery Trial (OAT).
AB  - AIMS: OAT randomised patients with an occluded infarct artery three to 28 days
      after myocardial infarction (MI). The study demonstrated that PCI did not reduce
      the occurrence of the primary composite endpoint of death, re-MI, and New York
      Heart Association class IV heart failure in comparison with patients assigned to
      optimal medical therapy alone (MED). In view of prior literature in similar
      cohorts showing fewer sudden cardiac deaths and less left ventricular (LV)
      remodelling, but excess re-MI with PCI, causes of death were analysed in more
      detail. METHODS AND RESULTS: Stepwise Cox regression was used to examine baseline
      variables associated with causes of death. The immediate and primary cause of
      death did not differ between 1,101 PCI and 1,100 MED patients. One-year
      cardiovascular death rates were 3.8% for the PCI group, and 3.7% for the MED
      group, and 0.9% per year for the next four years in both groups. Five of six
      cases of cardiac rupture occurred in patients undergoing PCI. CONCLUSIONS: In
      stable post-MI patients with occlusion of the infarct-related artery, PCI did not
      change the rate or cause of death. The observation that the majority of cardiac
      ruptures occurred in patients undergoing PCI deserves further investigation.

PMID- 20142186
TI  - Radial approach for percutaneous coronary intervention.

PMID- 20142187
TI  - AsiaPCR/SingLIVE, a new evolution, among others for the PCR community.

PMID- 20142188
TI  - Cost effectiveness of coronary revascularisation.

PMID- 20142189
TI  - Minutes and handbooks.

PMID- 20142190
TI  - Gender-based issues in interventional cardiology: a consensus statement from the
      Women in Innovations (WIN) initiative.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality in women, yet
      studies have suggested that it is often under-recognized. Of particular concern
      is the apparent suboptimal treatment of women in comparison to men, with less
      revascularisation and use of evidence-based medications. The Women in Innovations
      group of cardiologists aims to highlight these issues and change perceptions to
      optimize the treatment of female patients with CVD, to support future research,
      and to encourage and guide training of female interventional cardiologists.

PMID- 20142191
TI  - The influence of gender on short- and long-term outcome after primary PCI and
      delivered medical care for ST-segment elevation myocardial infarction.
AB  - AIMS: Despite the advances in treatment for acute ST-elevation myocardial
      infarction (STEMI) during the past decades for both men and women, most previous
      studies reported on significantly higher unadjusted in-hospital and long-term
      mortality rates among women compared with men. Most of these studies have been
      performed in the (pre-)thrombolytic and early post-thrombolytic era. Many studies
      reported on myocardial infarction or acute coronary syndromes and did not
      specifically address STEMI. Moreover, the association of gender, quality of care
      and mortality has not been systematically assessed. METHODS AND RESULTS: Early as
      well as long-term clinical outcome and delivered quality care was evaluated in an
      unselected cohort of 3,277 (2,367 men and 910 women) consecutive STEMI patients
      treated by primary PCI in a tertiary referral institution between January 1995
      and 2006. Mean follow-up was 3.2+/-2.2 years. The unadjusted early and late
      hazards of mortality were not significantly different between men and women (30
      days HR 0.87; 95%CI 0.67-1.12; 3-year HR 0.87; 95%CI 0.71-1.10), despite more
      adverse clinical characteristics in women. Gender was not an independent
      predictor for mortality and adjustment for covariates did not alter these
      results. Quality of care was similar between both sexes. CONCLUSIONS: Despite
      higher age and more disadvantageous clinical characteristics, unadjusted early as
      well as long-term mortality in women with STEMI treated by primary PCI was equal
      compared with men. Women have longer ischaemic times compared with men but not
      due to a difference in delivered care. Quality of care before, during and after
      reperfusion was equal for men and women.

PMID- 20142192
TI  - A pooled gender based analysis comparing the XIENCE V(R) everolimus-eluting stent
      and the TAXUS paclitaxel-eluting stent in male and female patients with coronary
      artery disease, results of the SPIRIT II and SPIRIT III studies: two-year
      analysis.
AB  - AIMS: To assess the safety and efficacy of the XIENCE V everolimus-eluting stent
      (EES) compared to the TAXUS paclitaxel-eluting stent (PES) in women at two years.
      METHODS AND RESULTS: In this pooled analysis, a cohort of 395 women and 906 men
      was studied by using patient level and lesion level clinical data from SPIRIT II
      and SPIRIT III studies. Women enrolled in these two studies had higher
      demographic and lesion risk characteristics than their male counterparts. In
      stent and in-segment late loss (LL) was significantly less in the women in the
      EES group compared to the women in the PES group (in-stent 0.15+/-0.44 mm vs.
      0.45+/-0.51 mm; P<0.01, in-segment 0.09+/-0.46 mm vs. 0.29+/-0.40 mm; P<0.01). In
      women, EES compared to PES resulted in significant reductions in major adverse
      cardiac events (MACE) (8.5% vs 16.4%; p=0.02) and in target vessel failure (TVF)
      (11.2% vs 19.5%; p=0.02) at two years. In men, a significant difference was seen
      in in-stent LL and in-stent % diameter stenosis (DS) favouring EES (in-stent LL
      0.14+/-0.33 mm vs. 0.28+/-0.47 mm; P<0.01, in-stent %DS 9.28+/-13.86 vs. 13.64+/
      18.31; P<0.01). MACE rates at two years were lower in males treated with EES
      compared to PES (6.7% vs. 10.9%; p=0.03). The interaction between gender and
      stent type was not found to be significant for MACE at two years. CONCLUSIONS: In
      this pooled analysis of two randomised trials, at two years, EES compared to PES
      resulted in reduced angiographic LL, fewer MACE and TVF events in women and
      reduced angiographic LL and %DS and fewer MACE events in men.

PMID- 20142193
TI  - Sex-related differences in patients undergoing percutaneous unprotected left main
      stenting.
AB  - AIMS: Percutaneous coronary intervention (PCI) is increasingly being used for
      unprotected left main (ULM) disease. Limited data are available on sex-related
      differences in this setting. We investigated gender-associated differences in
      patients undergoing stent-based PCI for ULM. METHODS AND RESULTS: We analysed
      baseline, procedural and long-term data of patients with ULM undergoing stent
      based PCI at participating centres. The primary end-point was the long-term rate
      of major cardiovascular events rate (MACE, i.e., the composite of death,
      myocardial infarction, or target lesion revascularisation). The study population
      included 1,452 cases, with 27.8% females and 72.2% males. Women were older, more
      frequently diabetic, hypertensive or presenting with an acute coronary syndrome,
      and thus with a higher EuroSCORE, but were less commonly treated with drug
      eluting stents (DES), in comparison to men (all p<0.01). After a median follow-up
      of 18 months, women showed an unadjusted higher risk of death (p=0.040), cardiac
      death (p=0.033), and the death/myocardial infarction (p=0.012). However, after
      multivariable adjustment, gender was no longer an independent predictor of death
      (hazard ratio=1.119 [0.804-1.558]), cardiac death (hazard ratio=1.045 [0.697
      1.567]), or death/myocardial infarction (hazard ratio=0.531 [0.192-1.465]), given
      the predominant role of age, diabetes and EuroSCORE as independent predictors and
      confounders of the gender-based comparison. CONCLUSIONS: Women undergoing PCI for
      ULM present more often with an acute coronary syndrome, are treated less
      frequently with DES, and have more adverse events, but these gender biases are
      not confirmed after adjusting for confounders. Thus, stent-based PCI for ULM
      offers similarly favourable clinical results in women as well as in men.

PMID- 20142194
TI  - Szabo technique versus conventional angiographic placement in bifurcations 010
      001 of Medina and in aorto-ostial stenting: angiographic and procedural results.
AB  - AIMS: The best strategy for stenting in bifurcations remains unclear. Szabo et al
      described a technique for accurate stent placement in bifurcations 010-001 or in
      aorto-ostial lesions. Its feasibility has been validated in animal models and
      small clinical series, but its safety and procedural results have never been
      compared to conventional positioning. METHODS AND RESULTS: In a retrospective
      search, 257 out of 2,596 intervened lesions corresponded to Medina 010 (108,
      42.0%)/001 (66, 25.7%) bifurcations or aorto-ostial lesions (83, 32.3%). Szabo
      was the initial choice in 78. Crude analysis showed significant differences
      between groups in several control variables, that disappeared after propensity
      score matching. Cross-over occurred in nine (11.7%) Szabo cases vs. no case in
      the conventional group. Two independent blinded investigators evaluated the
      angiographic result immediately after stent deployment. Szabo reduced the
      incidence of stent malpositioning (6.4% vs. 41.0%, p=0.000001), protrusion in the
      non-stented vessel/aorta (6.4% vs. 34.6%, p=0.00003) and incomplete scaffolding
      of the plaque (0.0% vs. 7.7%, p=NA). No significant differences regarding
      complications, procedural success or procedural complexity were observed after 30
      days follow-up. CONCLUSIONS: The Szabo technique reduces the incidence of
      angiographic malpositioning in Medina 010/001 bifurcations and aorto-ostial
      lesions, without increasing procedural complications.

PMID- 20142195
TI  - Jailed balloon protection: a new technique to avoid acute side-branch occlusion
      during provisional stenting of bifurcated lesions. Bench test report and first
      clinical experience.
AB  - AIMS: Provisional stenting with drug-eluting-stents is actually adopted to treat
      most of bifurcated lesions. A major drawback of this technique is the risk of
      side-branch (SB) closure after main vessel (MV) stenting. METHODS AND RESULTS: We
      set-up, and bench tested, a novel technique for SB protection based on the
      placement of a balloon in the SB during MV stenting. The uninflated balloon,
      which remains jailed under the stent struts, serves to reduce both carina and
      plaque shifts due to its SB ostium spatial occupation. If SB flow is preserved
      after MV stenting, the jailed balloon is removed uninflated. If the SB becomes
      occluded after MV stenting, the jailed balloon may either be used as a marker and
      a favourable angle modifier to facilitate rewiring or can be dilated to try to
      restore SB flow. SB rewiring and kissing balloon inflation must be performed to
      correct stent deformation or malapposition. This novel technique has been
      successfully adopted in 20 patients with complex (55% unprotected left main, 85%
      Medina 1,1,1 lesions) true bifurcated lesions undergoing drug-eluting-stent
      implantation. CONCLUSIONS: The jailed balloon protection is a novel technique
      aimed at improving SB protection during provisional stenting of bifurcated
      lesions considered at high risk of SB compromise after MV stenting.

PMID- 20142196
TI  - "Inverted" provisional T stenting, a new technique for Medina 0,0,1 coronary
      bifurcation lesions: feasibility and follow-up.
AB  - AIMS: Isolated, high-grade coronary bifurcation lesions located at the side
      branch (SB) ostium (Medina type 0,0,1) are uncommon and their specific treatment
      has not been described. METHODS AND RESULTS: We have developed an "inverted"
      technique for the treatment of these lesions, derived from the usual provisional
      T stenting. We implant the stent from the proximal main branch through the SB,
      with reopening of the strut through the distal main branch (DMB) and systematic
      final kissing balloon. We retrospectively reviewed results in 40 patients. The
      procedural success was 100%, no failure was observed to rewire the DMB or perform
      the kissing balloon, and a second sent was implanted in the DMB in only three
      patients (7.5%). No death, myocardial infarction, stent thrombosis or repeat
      revascularisation occurred within the first 30 days of follow-up. At a mean of
      22+/-14 months, three patients underwent repeat percutaneous coronary
      intervention (7.5%), with target lesion restenosis (n=2; 5%), other vessel
      treated (n=1, 2.5%), target lesion revascularisation (n=1; 2.5%), and target
      vessel revascularisation (n=1, 2.5%). CONCLUSIONS: The "inverted" provisional T
      stenting technique was safe and highly effective in the management of Medina
      0,0,1 coronary bifurcation lesions. Larger trials are needed before its routine
      application can be recommended.

PMID- 20142197
TI  - The Highway Technique: a new stenting technique to treat coronary bifurcation
      lesions.
AB  - AIMS: We report a new stenting technique which was employed in 12 patients to
      treat coronary bifurcation lesions. METHODS AND RESULTS: A stent is positioned in
      the main vessel together with a balloon in the side branch, which is positioned
      slightly proximal to the main vessel stent that also has enough length to cover
      the side branch ostium. Both the stent in the main vessel and the balloon in the
      side branch are inflated simultaneously. Following deflation, a double lumen is
      created in the main vessel, proximal to the bifurcation. The stent balloon is
      removed with the side branch balloon left deflated in its initial position. The
      main vessel is rewired with a third guidewire. The side branch balloon and
      guidewire are removed. The initial guidewire in the main vessel is directed to
      the side branch. A balloon is advanced and inflated in the side branch to dilate
      the struts of the main vessel stent that will provide the side branch entrance.
      The side branch balloon is left in place. A size matched balloon is advanced on
      the third guidewire that was advanced in the main vessel and inflated inside the
      stent with high pressure. Finally, kissing balloon inflation is performed at the
      bifurcation. Provisional stenting of the side branch can be performed when
      necessary. Final kissing balloon inflation is recommended after stenting of the
      side branch. CONCLUSIONS: As a new coronary bifurcation stenting method, the
      Highway Technique has some advantages in side branch protection, with favourable
      immediate and 30-day clinical outcomes.

PMID- 20142198
TI  - Cost-effectiveness of the Endeavor stent in de novo native coronary artery
      lesions updated with contemporary data.
AB  - AIMS: The Endeavor zotarolimus-eluting coronary stent has been shown to reduce
      the restenosis rate compared to bare metal stents and has impacted other clinical
      measures such as mortality, acute myocardial infarctions (AMI) and target vessel
      revascularisation (TVR). METHODS AND RESULTS: Using pooled efficacy data from the
      Endeavor clinical trial programme, a model was developed to compare the cost
      effectiveness of the Endeavor drug eluting stent (DES) with the Driver bare meal
      stent (BMS) over a four year time period. Endeavor was more costly but had an
      improved clinical outcome compared to Driver BMS over four years with a 4%
      reduction in deaths, 33% reduction in AMI and a 45% reduction in TVR. Late stent
      thrombosis was the only event showing an increased incidence for Endeavor of 0.2%
      compared to 0% for Driver. The incremental cost effectiveness ratio was
      pound3,757/quality adjusted life years (QALY). CONCLUSIONS: Although much
      controversy has surrounded the appropriate way to assess the cost effectiveness
      of DES technology, a comprehensive analysis is presented and this suggests that
      by using extended clinical trial data out to four years, the Endeavor DES in
      particular, but DES technologies in general, are cost-effective approaches to
      percutaneous coronary intervention.

PMID- 20142199
TI  - Device closure of residual shunt after percutaneous closure of patent foramen
      ovale.
AB  - AIMS: To summarise our experiences of device closure of residual shunt after
      transcatheter closure of patent foramen ovale (PFO). METHODS AND RESULTS: Since
      October 1997 implantation of a second closure device was attempted in 40 patients
      with a moderate or large residual shunt after implantation of a PFO closure
      device. The mean age of the patients was 51 years. Implantation of a second
      closure device was technically successful in 39/40 patients (98 %). The following
      devices were implanted: Premere (n=20), Amplatzer PFO (n=13), STARFlex (n=4),
      Helex (n=1), Angelwings (n=1). During a mean follow-up of 36+/-29 months complete
      closure was achieved in 27 patients (69 %). The remaining shunt was small in nine
      patients, moderate in one and large in two. One patient with a moderate and one
      patient with a large residual shunt received a third device. The third patient
      was sent to surgery. One patient died 21 days after implantation of a third
      closure device due to acute pericardial tamponade. No other complications
      occurred. CONCLUSIONS: Transcatheter implantation of a second closure device
      after PFO closure is feasible. Complete closure can be achieved in the majority
      of patients.

PMID- 20142200
TI  - Effect of PCI on inflammatory markers, adiponectin and insulin resistance.
AB  - AIMS: Percutaneous coronary interventions (PCI) evoke an inflammatory response
      and have been reported to decrease adiponectin levels. If persistent over time,
      the inflammatory response and low adiponectin levels would induce insulin
      resistance, rendering PCI potentially hazardous for glucose metabolism. We
      investigated whether PCI decreased insulin sensitivity after one month and if so,
      whether this was related to a lasting elevation of inflammatory markers and
      decrease in adiponectin levels. METHODS AND RESULTS: Insulin sensitivity
      (euglycemic hyperinsulinaemic clamp) was measured in 19 patients with stable
      coronary artery disease before and one month after PCI. Also, levels of
      inflammatory mediators and adiponectin were assessed. Insulin sensitivity was not
      affected by the PCI procedure. There were no persistent increases in IL-6, hs-CRP
      and adiponectin levels after PCI. CONCLUSIONS: The inflammatory response seen
      immediately after PCI does not translate to a medium-term negative effect on
      insulin action.

PMID- 20142201
TI  - A comparison of clinical presentations, angiographic patterns and outcomes of in
      stent restenosis between bare metal stents and drug eluting stents.
AB  - AIMS: This paper studies in-stent restenosis (ISR) after percutaneous coronary
      intervention (PCI) following bare-metal stent (BMS) and drug-eluting stent (DES)
      in all consecutive patients between 2004 and 2007 undergoing PCI for ISR lesions
      at our centre. METHODS AND RESULTS: We compared the clinical presentation,
      pattern and angiographic outcomes in 838 patients with BMS ISR (487) and SES ISR
      (351). About 18% of the patients presented with acute coronary syndrome with 2%
      presenting as ST elevation myocardial infarction, similar in both groups.
      Angiographic pattern was predominantly focal with SES ISR (47%SES ISR vs. 19% BMS
      ISR; p<0.001) and diffuse with BMS ISR (SES ISR 16% vs. BMS ISR 36%; p=0.003). In
      our series the use of balloon angioplasty was higher for the treatment of SES ISR
      patients as compared to BMS ISR (41.6% vs. 18.3%; p<0.001) and the usage of stent
      was higher in BMS ISR patients (38.6% vs. 23.4%; p<0.001). Angiographic recurrent
      restenosis with conventional treatment in a consecutive series of patients was
      38.6% and target lesion revascularisation was seen in 33.6%. These outcomes were
      seen slightly higher in SES ISR group (41.1% vs. 36.9%, p=ns). We have identified
      unstable angina at presentation (OR 3.02; 95%CI: 1.58-5.77, p=0.001), focal
      pattern of ISR (OR 0.50; 95% CI: .25-.99, p=0.04), stent usage (OR .25; 95% CI
      .13-.47, p<0.001), and baseline% diameter stenosis (OR1.03; 95%CI: 1.03-1.06,
      p=0.01) as independent predictors of BMS ISR recurrent restenosis. Unstable
      angina, focal pattern of ISR, reference vessel diameter, and% diameter stenosis
      were shown to be independent predictors of SES ISR. CONCLUSIONS: ISR is not a
      benign condition, and one fifth of the patients presented with acute coronary
      syndrome. The pattern of restenosis is predominantly non-focal with BMS ISR and
      focal with SES ISR. Recurrent restenosis rates are high following conventional
      treatment and further optimal therapies mainly with SES ISR needs to defined.

PMID- 20142202
TI  - Pulse wave analysis during instructed breathing as an indicator of significant
      coronary artery disease.
AB  - AIMS: Previous studies indicated that fluctuations in photoplethysmograph (PPG)
      amplitude may predict coronary artery disease (CAD). The respiratory modulation
      response (RMR) is derived from spectral analysis of the PPG signal during
      instructed breathing. We sought to evaluate the RMR obtained from the fingertip
      as a predictor of significant CAD. METHODS AND RESULTS: RMR was calculated as the
      relative change in the respiratory modulation of the PPG, in response to
      breathing at 0.1Hz. RMR results of 97 consecutive patients (age 62+/-12 years,
      77% male) were compared with their angiograms. Coronary lesions with diameter
      stenosis >50% that required revascularisation were classified significant. RMR
      was analysed after 20 sec. of spontaneous breathing, followed by 70 sec. of
      breathing at 0.1Hz. The test was repeated post procedure in 76 patients. RMR was
      lower in patients with significant CAD compared to those with non-significant
      (16.3+/-20.1; n=66 vs. 40.6+/-16.9; n=31, P<0.001). It improved after successful
      angioplasty (from 15.0+/-19.0 to 40.0+/-18.9; P<0.001) and did not change after
      diagnostic catheterisation. Using receiver operating characteristic analysis, we
      identified RMR<30% (sensitivity 79%, specificity 87%; positive predictive value
      93%; negative predictive value 66%) to be the optimal cutoff for predicting
      significant CAD. CONCLUSIONS: The RMR is a novel, non-invasive parameter for the
      assessment of significant CAD.

PMID- 20142203
TI  - Effect of drug-eluting stents in patients with acute ST-segment elevation
      myocardial infarction undergoing percutaneous coronary intervention: a meta
      analysis of randomised trials and an adjusted indirect comparison.
AB  - AIMS: The role of drug-eluting stent (DES) remains an unsettled issue in patients
      with ST-segment elevation myocardial infarction (STEMI). Therefore, we performed
      a meta-analysis of randomised trials to evaluate the clinical outcome of DES as
      compared with bare-metal stent (BMS) after percutaneous coronary intervention
      (PCI). METHODS AND RESULTS: We undertook a literature search until July 2009.
      Thirteen clinical trials met inclusion criteria, with 7,244 patients enrolled. Up
      to 1-year, patients treated with DES as compared with BMS experienced less target
      vessel revascularisation (TVR) (5.11% versus 11.19% respectively, p<0.00001) and
      recurrent myocardial infarction rates (3.03% versus 3.70% respectively, p=0.02).
      In addition, no significant differences were found in terms of cardiac death
      (2.80% versus 3.52%, p=0.21) and stent thrombosis (2.65% versus 2.76%, p=0.37).
      Using the adjusted indirect comparison, a significant difference between
      sirolimus- and paclitaxel-eluting stent was found when TVR was evaluated (OR [95%
      CI] =0.59 [0.40-0.89], p=0.01), without differences in other clinical outcomes.
      CONCLUSIONS: In patients undergoing PCI for STEMI, treatment with DES is
      associated with decreased TVR and myocardial infarction rates, without increasing
      cardiac death or stent thrombosis occurrence. Sirolimus-eluting stent is
      associated with a greater TVR reduction as compared to paclitaxel-eluting stent.

PMID- 20142204
TI  - How should I treat an unusual referral for heart transplantation?
AB  - BACKGROUND: A 55 years old man was referred for cardiac transplantation because
      of intractable angina and fatigue. INVESTIGATION: Physical examination,
      laboratory test, echocardiography, exercise ECG, MRI and coronary arteriography.
      DIAGNOSIS: Multiple coronary artery fistulae. MANAGEMENT: Beta-blockers,
      angiotensin-converting enzyme inhibitor ICD.

PMID- 20142205
TI  - Endovascular carotid interventions.

PMID- 20142206
TI  - Myocardial infarction adjudication in contemporary all-comer stent trials:
      balancing sensitivity and specificity. Addendum to the historical MI definitions
      used in stent studies.

PMID- 20142207
TI  - Comments on the article by Routledge et al "Three-year clinical outcome of
      percutaneous treatment of bifurcation lesions in multivessel coronary artery
      disease with the sirolimus-eluting stent: insights from the Arterial
      Revascularisation Therapies Study, part II (ARTS II)".

PMID- 20142208
TI  - The times, they are a-changing... constantly!

PMID- 20142209
TI  - Are animal experiments the crux for decision making in whether new heart valves
      can be brought to clinical practice?

PMID- 20142210
TI  - Drug-eluting stents for saphenous vein graft lesions: useful or harmful?

PMID- 20142211
TI  - Bleeding after coronary stenting in patients on oral anticoagulation: who is
      guilty?

PMID- 20142212
TI  - Triple therapy: the future or from the past?

PMID- 20142213
TI  - Is it time to consider the Movahed classification as the preferred classification
      for coronary bifurcation lesions?

PMID- 20142214
TI  - "Rehabilitation" after PCI: nonsense or the only way to achieve lasting results?

PMID- 20142215
TI  - Thirty-day outcome and vascular complications after transarterial aortic valve
      implantation using both Edwards Sapien and Medtronic CoreValve bioprostheses in a
      mixed population.
AB  - AIMS: Transcatheter aortic valve implantation (TAVI) is performed through a
      transarterial approach with encouraging results in "one-type valve" registries.
      We report 30-day data from a mixed population of patients treated with either
      Medtronic CoreValve (MCV) or Edwards SAPIEN (ES) valves. METHODS AND RESULTS:
      Forty-five patients had TAVI via the transarterial approach (21 MCV and 24 ES).
      Mean age was 81.8+/-4.2 years, Logistic EuroSCORE was 25.2+/-8.4%. Procedural
      success rate was 97.8%. In-hospital death rate was 4.4%. Vascular complication
      rate was 8.9%. Of MCV patients, 28.6% had a permanent pacemaker vs. 4.2% of ES
      patients; p=0.02. No additional deaths were observed between discharge and 30
      days. NYHA functional class was improved at 30-days: 2.07+/-0.4 vs. 3.09+/-0.05,
      p<0.0001. Mean transvalvular gradient was lower: 9.5+/-3.28 mmHg vs. 41.9+/-14
      mmHg, p<0.0001. Overall 30-day MACE rate was 8.9%, similar between MCV and ES
      patients. CONCLUSION: A routine policy of TAVI using both MCV and ES valves is
      feasible without any worsening of procedural success rates and 30-day outcomes. A
      wider population of high risk patients with aortic stenosis can be offered a
      transarterial treatment. This could be the next standard of care for teams
      performing TAVI.

PMID- 20142216
TI  - Vascular complications of transfemoral aortic valve implantation with the Edwards
      SAPIEN prosthesis: incidence and impact on outcome.
AB  - AIMS: Vascular complications remain the main limitation of transfemoral aortic
      valve implantation. Based on a single-centre experience, we aim to detail the
      type, management and impact of those vascular complications. METHODS AND RESULTS:
      From October 2006 to January 2009, 54 transfemoral aortic valve implantations
      were performed using the Edwards SAPIEN prosthesis. Nine patients (16.7%)
      developed vascular complications. Five patients (9.3%) had ruptures which
      necessitated a surgical bypass. Four patients (7.4%) had dissection necessitating
      repair using stenting in all four patients and associated bypass in two of them.
      Vascular complications led to death in one patient (1.9%), reintervention in one
      (1.9%), and transfusions in seven (13%). Five vascular complications occurred in
      the first 20 patients (25%), and only four in the last 34 (12%). CONCLUSIONS:
      Vascular complications of transfemoral aortic valve implantation are frequent and
      seem to be influenced by experience. They are associated with a high need for
      transfusion and could lead to major events such as death or reintervention. These
      findings highlight the importance of a multidisciplinary approach for patient
      selection and management of the procedure.

PMID- 20142217
TI  - Vascular complications with transcatheter aortic valve implantation using the 18
      Fr Medtronic CoreValve System: the Rotterdam experience.
AB  - AIMS: Transcatheter aortic valve implantation (TAVI) requires large bore
      catheters. Access site complications, therefore, can be a concern. The aim of
      this study is to present the 30-day incidence of major and minor vascular
      complications in patients treated with the third generation 18 Fr Medtronic
      CoreValve System. METHODS AND RESULTS: We prospectively evaluated the vascular
      complications occurring in all patients treated with the 18 Fr Medtronic
      CoreValve System between October 2006 and October 2009 in the Thoraxcenter using
      various proposed definitions. Ninety-nine consecutive patients were treated with
      TAVI using the 18 Fr Medtronic CoreValve System. Vascular events were encountered
      in 13 patients (13%), seven of these cases (54%) were related to incomplete
      arteriotomy closure with the Prostar device which is the default access closure
      technique in our centre. Depending on how major vascular complications were
      defined, the incidence varied from 4 to 13%. Blood transfusions in combination
      with surgical or percutaneous intervention were required in eight cases.
      CONCLUSIONS: Transcatheter aortic valve implantation with the 18 Fr Medtronic
      CoreValve System(R) has a 4 to 13% vascular complications' rate. More than half
      of the vascular events were due to incomplete Prostar arteriotomy closure,
      despite its use by experienced operators. Current percutaneous closure devices
      for these large arteriotomies seems suboptimal. Uniformity in how to define TAVI
      related vascular complications is needed.

PMID- 20142218
TI  - A clinical protocol for analysis of the structural integrity of the Medtronic
      CoreValve System frame and its application in patients with 1-year minimum follow
      up.
AB  - AIMS: The optimal clinical protocol to detect fractures of transcatheter aortic
      valves is unknown. To the best of our knowledge, there are no published reports
      describing stent or frame fractures following transcatheter aortic valve
      implantation. The purpose of this study is two-fold: (1) to determine the optimal
      fluoroscopic protocol to identify potential fractures of the Medtronic CoreValve
      frame; and (2) to implement this protocol in the analysis of the fluoroscopic
      films of patients implanted with the CoreValve device with 1-year minimum follow
      up. METHODS AND RESULTS: Considering the resolution of fluoroscopy (approximately
      0.2 mm), we used a 0.2 mm diamond-cutter to create a single fracture in a single
      strut of two CoreValve frames. An intact CoreValve prosthesis was used as
      control. These prostheses were subsequently implanted in post-mortem heart
      specimens. A protocol involving still frames and rotational (left-right and
      cranial-caudal) fluoroscopic imaging was then applied to the heart specimens. The
      experimentally induced fractures were detectable on the rotational cine runs
      (left-right and cranial-caudal); in some of the fixed acquisition sequences,
      however, the fractures were undetectable. The fluoroscopic protocol was
      retrospectively applied to the films of 58 patients who underwent implantation
      with the CoreValve System between October 2005 and August 2008 and had at least 1
      year follow-up. The mean and median follow-up times were 22 months and 24 months,
      respectively (range 12 to 36 months). Rotational cine films (only left-right
      lateral) were available in 39 patients (60%). No frame fractures of the CoreValve
      frame were identified. CONCLUSIONS: Rotational cine runs in the left-right and
      cranial-caudal directions should be mandatory in the clinical assessment of the
      structural integrity of the CoreValve frame. No frame fractures were identified
      in 58 patients implanted with the Medtronic CoreValve device with 2-year mean
      follow-up.

PMID- 20142219
TI  - MISAGO 1: first-in-man clinical trial with Misago nitinol stent.
AB  - AIMS: To evaluate a newly developed self-expanding Misago (Terumo Corp., Tokyo,
      Japan) nitinol stent with rapid exchange delivery catheter for the treatment of
      stenotic or occluded superficial femoral (SF) or popliteal arteries. METHODS AND
      RESULTS: MISAGO 1 clinical trial enrolled 55 patients undergoing percutaneous
      intervention of totally occluded or stenotic lesions in SF or popliteal arteries
      treated with the implantation of 81 stents in five centres across Europe. Primary
      endpoint was restenosis rate at six months assessed by duplex sonography.
      Patients (67% male) were 68+/-9 years old, 60% were smokers and 31% had diabetes.
      Clinical symptoms of ischaemia were present in all patients. Average lesion
      length was 85+/-50 mm, 64% were totally occluded and 38% classified as TASC C or
      D. The technical success rate was 100% while the procedural success rate was
      98.2% without death, MI, stroke, or major bleeding. At six months follow-up the
      restenosis rate was 8.5%. One patient (1.8%) died of bronchial carcinoma and two
      (3.6%) underwent target vessel revascularisation. Mean ankle brachial index
      improved from 0.70 at baseline to 0.95 at six months while walking capacity on
      treadmill test improved with an average of 147 m. Rutherford index at six months
      demonstrated improvement of 72%, without any patients having symptom
      deterioration. One case of stent fracture was observed. CONCLUSIONS: The results
      from this first-in-man study indicate good safety and short to medium term
      efficacy profile of the Misago nitinol stent.

PMID- 20142220
TI  - Long-term clinical outcomes with the next-generation Resolute Stent System: a
      report of the two-year follow-up from the RESOLUTE clinical trial.
AB  - AIMS: The 12-month results of RESOLUTE were favourable for the new Resolute
      stent. Two-year safety and efficacy results from RESOLUTE have been evaluated and
      are now reported. METHODS AND RESULTS: RESOLUTE was a prospective, multicentre,
      non-randomised, single-arm, controlled trial of the Resolute stent in 139
      participants with symptomatic ischaemic heart disease due to single de novo
      lesions in a native coronary artery. The 2-year rates of MACE (all-cause death,
      myocardial infarction, emergent cardiac bypass surgery, and target lesion
      revascularisation [TLR]), death, late stent thrombosis, target vessel
      revascularisation (TVR), and target vessel failure (TVF) were assessed. Clinical
      events included two MACE (one TLR; one non-cardiac death) occurring between year
      one and two resulting in cumulative 2-year TLR, TVR, and TVF rates of 1.4%, 1.4%,
      and 7.9%, respectively. One possible stent thrombosis event occurred in the first
      year after stent implantation however no late or very late ARC-defined definite
      and probable stent thromboses occurred through two years. CONCLUSIONS: The 2-year
      data from RESOLUTE demonstrated no safety concerns including no late stent
      thrombosis or loss of effectiveness with the Resolute stent. The finding that few
      events occurred in year two is encouraging, yet requires verification in a larger
      population.

PMID- 20142221
TI  - Endothelial progenitor cell capture stent implantation in patients with ST
      segment elevation acute myocardial infarction: one year follow-up.
AB  - AIMS: The Genous endothelial progenitor cell (EPC) capture stent is a
      bioengineered R stent coated with immobilised antibodies on its stent struts to
      allow for the capture of circulating EPCs to promote rapid endothelisation. We
      assessed the impact of this stent in the primary percutaneous coronary
      intervention (PCI) of patients with acute ST-elevation myocardial infarction
      (STEMI) and examined its long term clinical outcomes. METHODS AND RESULTS: All
      patients with acute STEMI without cardiogenic shock who underwent primary PCI
      between January 2005 and April 2007 and received the stent were enrolled in the
      study. The study endpoints were major adverse cardiac events (MACE) defined as
      death, MI and target vessel revascularisation (TVR) at 30 days, six months and
      one year. A total of 321 enrolled patients received 357 EPC capture stents during
      the study period. The cohort comprises 81.0% males with mean age of 54.6+/-11.6
      years. The mean stent length used was 20.98+/-5.50 mm and mean stent size was
      2.99+/-0.32 mm. Ninety-four percent of patients achieved Thrombolysis in
      Myocardial Infarction (TIMI) 3 flow post-procedurally. The cumulative MACE rate
      was 8.1% at 30 days, 10.0% at six months and 12.2% at one year. There was one
      patient who developed acute stent thrombosis and another two with subacute stent
      thromboses. No late thrombosis or late cardiac mortality was observed in our
      cohort. The need for TVR was 4.4% at one year. CONCLUSIONS: The use of EPC
      capture stents in patients who underwent primary PCI for STEMI is safe and showed
      good clinical outcomes, with low rates of TVR and no late stent thrombosis.

PMID- 20142222
TI  - Long-term clinical follow-up of drug-eluting stent restenosis treatment:
      retrospective analysis from two high volume catheterisation laboratories.
AB  - AIMS: To evaluate clinical outcome of patients undergoing repeated percutaneous
      coronary intervention (PCI) for drug-eluting stent (DES) restenosis. METHODS AND
      RESULTS: We identified 213 patients who underwent re-PCI for DES restenosis. The
      study population was divided in two groups according to the treatment strategy:
      94 patients were treated with at least one repeat DES implantation (DES-sandwich
      group); 119 patients were treated with balloon angioplasty alone (BA group).
      Diffuse pattern of restenosis was more frequent in DES-sandwich group (34.0% vs.
      17.6%; P=0.006). During a median follow-up of 20.2 months (interquartile range
      13.7 to 30.1), the incidence of cardiac death was 6.5% in the DES-sandwich and
      2.5% in the BA group (P=0.18), the incidence of myocardial infarction 6.5% and
      0.8% (P=0.04), and the incidence of TLR 13% and 10.9% (P=0.63), respectively.
      After adjustment for angiographic characteristics, DES-sandwich strategy tended
      to be associated with a higher rate of myocardial infarction (OR 8.2, 95%CIs[0.9
      69.6]; P=0.05). By multivariate analysis, early and diffuse pattern of restenosis
      were found as predictors of adverse outcome at follow-up (OR 4.7, 95%CI[2.2-9.6],
      P<0.001; OR 2.3, 95%CI[1.1-4.8], P=0.02, respectively). CONCLUSIONS: A default
      strategy of repeat DES implantation does not seem to be advantageous and could be
      associated with a higher rate of myocardial infarction.

PMID- 20142223
TI  - Diffuse atherosclerotic left main coronary artery disease unmasked by fractal
      geometric law applied to quantitative coronary angiography: an angiographic and
      intravascular ultrasound study.
AB  - AIMS: Angiographic analysis of left main coronary artery (LMCA) stenosis can be
      hindered by the lack of any reference segment when the LMCA is short or there is
      diffuse atheroma. Fractal geometric law (FGL) enables the theoretic diameter of
      one bifurcation vessel to be calculated from those of the other two
      (Dmother=0.678*(Ddaughter1+Ddaughter2). Applied to the LMCA, the FGL can help the
      quantification of stenoses. METHODS AND RESULTS: Fifty-two patients with
      angiographically mild focal LMCA disease (n=14) or normal to nearly normal LMCA
      (n=38) who had undergone intravascular ultrasound (IVUS) were included. IVUS
      analysis confirmed all 14 focal stenoses (group C); of the 38 angiographically
      normal patients, however, 10 were found to present diffuse LMCA disease (group
      B), the remaining 28 showing a truly healthy LMCA (group A). LMCA stenosis in
      groups A,B and C was respectively 3%,4% and 42% on usual quantitative coronary
      angiography(QCA) and 5%, 31% and 43% on QCAfractal applying the FGL. In cases of
      diffuse atheroma, the FGL corrected the underestimation of LMCA diameter, which
      averaged 1.2 mm. conclusions: Angiographic underestimation of LMCA stenosis can
      be corrected by applying the FGL to obtain a theoretic LMCA diameter, thereby
      unmasking any diffuse atherosclerotic LMCA disease, or to quantify focal stenosis
      more precisely where the adjacent segments are also pathological.

PMID- 20142224
TI  - Role of rheolytic thrombectomy in massive pulmonary embolism with
      contraindication to systemic thrombolytic therapy.
AB  - AIMS: Mortality of massive pulmonary embolism remains exceedingly high despite
      thrombolytic therapy. Despite initial encouraging results, rheolytic thrombectomy
      has not been considered the first choice of treatment in the current European
      Guidelines for massive pulmonary embolism, even in cases of major
      contraindication to thrombolysis. Our objective was to assess the efficacy of
      rheolytic thrombectomy in the specific treatment of massive pulmonary embolism
      with contraindication to systemic thrombolytic therapy. METHODS AND RESULTS:
      Between January 2003 and April 2008 a total of 10 patients with massive pulmonary
      embolism referred for rheolytic thrombectomy were included. Clinical data
      including medical history, haemodynamic status, procedural characteristic, in
      hospital complications and survival were collected. Seven patients survived after
      undergoing the procedure, three patients died in during their initial
      hospitalisation however, two of these deaths were not attributable to the
      pulmonary embolism or the procedure. Rheolytic thrombectomy resulted in reduction
      of mean pulmonary artery pressures from 34.6+/-13.1 mmHg to 26.9+/-8.2 mmHg
      immediately following the procedure. Additionally, the Miller index improved from
      22.4+/-2.8 to 9.8+/-2.7. There were no periprocedural bleeding complications
      associated with the procedure. CONCLUSIONS: Rheolytic thrombectomy might be an
      effective and safe treatment for massive pulmonary embolism when systemic
      thrombolytic therapy is contraindicated. These data form the basis for further
      clinical investigation of this novel therapy among patients with massive
      pulmonary embolism.

PMID- 20142225
TI  - Drug-eluting stents in saphenous vein graft interventions: a systematic review.
AB  - AIMS: A systematic review of the outcomes after drug-eluting stents (DES)
      implantation in saphenous vein grafts (SVGs) was performed. METHODS AND RESULTS:
      The majority of the 33 published studies were retrospective with only two
      prospective randomised trials. Late loss and binary restenosis was reduced
      compared to bare metal stents (BMS) in all seven studies with angiographic follow
      up. With the exception of one study there was no difference in mortality,
      myocardial infarction, or stent thrombosis between BMS and DES. The need for
      repeat target vessel or lesion revascularisation was lower in the DES arm in
      approximately half the published studies and similar in the remaining studies.
      CONCLUSIONS: Until data from large, prospective, randomised-controlled studies
      become available, DES implantation in SVGs appears to be safe and, although not
      yet definitively proven, likely to reduce angiographic restenosis and the need
      for repeat target lesion revascularisation.

PMID- 20142226
TI  - In vivo intravascular ultrasound analysis of the absorption rate of the Angio
      Seal vascular closure device in the porcine femoral artery.
AB  - AIMS: Device-based arterial closure is currently used to achieve haemostasis
      following percutaneous intervention. Little is known about the in vivo patterns
      of device absorption. We aimed to characterise the absorption dynamics following
      implantation of the Angio-Seal VIP closure device (AVCD) (St. Jude Medical, St.
      Paul, MN, USA) by using serial intravascular ultrasound (IVUS) and histology.
      METHODS AND RESULTS: Eleven AVCD were implanted following 6 Fr femoral arterial
      sheath in six pigs. Using carotid access, angiograms and IVUS were performed at
      baseline, 3, 5, 7, 14, 30 and 42 days following deployment. At termination,
      arteries were processed for histology at 14 (n=3), 30(n=4) and 42 days (n=4). By
      IVUS, following implantation the intravascular component (IC) area remained
      unchanged up to 14 days and decreased by 50% at 30 days and 95% by 42 days. By
      histology, there was a progressive decline in the IC area at 14 days and decrease
      by 30% at 30 days and 77% by 42 days. Histology demonstrated almost complete
      absorption of the IC and no signs of severe chronic granulomatous inflammation.
      CONCLUSIONS: IVUS serial imaging demonstrated almost complete absorption of the
      IC by 42 days in normal porcine femoral arteries. There was no evidence of severe
      chronic granulomatous vascular inflammation demonstrated by histology.

PMID- 20142227
TI  - Histopathologic evaluation of nitinol self-expanding stents in an animal model of
      advanced atherosclerotic lesions.
AB  - AIMS: The histologic response to self-expanding stent implantation into advanced
      atherosclerotic lesions has not been systematically investigated. We tested the
      hypothesis of whether gradual expansion of advanced atherosclerotic plaques by
      self-expanding stents would be an appropriate method to seal atherosclerotic
      lesions without causing plaque disruption as is usually observed with balloon
      expandable stents. METHODS AND RESULTS: Twelve New Zealand white rabbits were fed
      an atherogenic diet (1% cholesterol) followed by arterial denudation and
      injection of washed autologous erythrocytes. Nitinol self-expanding stents of two
      different stent designs and strengths (n=12 for SX and n=12 for Micro-SX) were
      implanted into the previously formed lesions within the abdominal aorta six weeks
      following injection of erythrocytes. Four weeks following stent implantation,
      animals were sacrificed, specimens harvested and processed for histology.
      Histomorphometry was performed on stented and adjacent non-stented regions.
      Atherosclerotic lesions were composed of foam cells, cholesterol clefts and
      necrotic plaque. While SX stents showed an unfavourable outcome with respect to
      vessel remodelling and the percentage of uncovered stent struts, Micro-SX stents
      had fewer uncovered stent struts, less positive remodelling and less plaque
      injury. CONCLUSIONS: Nitinol Micro-SX self-expanding stents might be a valuable
      approach to seal high risk atherosclerotic lesions.

PMID- 20142228
TI  - First-in-man implantation of a novel percutaneous valve: a new approach to
      medical device development.
AB  - AIMS: To present our experience of 'first-in-man' implantation of a new
      percutaneous pulmonary valve into a dilated pulmonary trunk, using patient
      specific data to influence the design of the device and ensure patient safety.
      METHODS AND RESULTS: A 42-year-old with severe pulmonary insufficiency underwent
      computed tomography assessment of his pulmonary trunk. This information was
      utilised to create computer and rapid prototyping models that were used to
      customise and test the device, which was subsequently implanted into the patient.
      Following the procedure, the clinical, haemodynamic and morphological success of
      this approach was determined. The new device was safely and successfully
      implanted as predicted by the pre-procedural modelling. There was excellent
      device stability, no stent fractures, no pulmonary incompetence and only trivial
      para-device leak at six months follow-up. The patient described marked
      symptomatic improvement. CONCLUSIONS: Safe, effective percutaneous pulmonary
      valve implantation is possible in a patient with a dilated, native pulmonary
      trunk. Our methodologies, which have evolved as a direct result of recent
      advances in four-dimensional imaging techniques, challenge the conventional
      stepwise pathway of bench and animal testing prior to human application, and may
      be safer and more relevant, potentially reducing the number of animal experiments
      necessary for testing new medical devices.

PMID- 20142229
TI  - Femoral artery puncture.

PMID- 20142230
TI  - Very late stent thrombosis of a NIR Advance bare metal stent nine years after
      implantation.

PMID- 20142231
TI  - Tako-Tsubo syndrome and reversible epicardial coronary spasm.

PMID- 20142232
TI  - First use in patients of a combined near infra-red spectroscopy and intra
      vascular ultrasound catheter to identify composition and structure of coronary
      plaque.

PMID- 20142234
TI  - Behavioral correlates of HPV vaccine acceptability in the 2007 Health Information
      National Trends Survey (HINTS).
AB  - The development of a prophylactic vaccine to prevent infection with oncogenic
      subtypes of human papillomavirus (HPV) is an important step in reducing cervical
      cancer incidence and mortality. However, national data indicate that only 37% of
      13- to 17-year-old females have initiated the vaccine series. Prior studies have
      examined demographic, medical history, and psychosocial variables associated with
      parental HPV vaccine acceptability, although few have investigated the behavioral
      correlates of vaccine acceptability. The primary purpose of the current study is
      to report on national acceptability of the HPV vaccine among U.S. adults with
      female children in the household and to investigate the health behavior
      correlates of vaccine acceptability. Data were drawn from the 2007 Health
      Information National Trends Survey (HINTS). The study sample comprised 1,383
      adults who reported having a female child under the age of 18 in their household
      (52% female, 59% white; mean age = 40 years). More than half (58%) reported they
      would have a daughter get the HPV vaccine, 25% were not sure, and 18% would not
      have a daughter vaccinated. Behavioral factors significantly associated with
      lower acceptance of the HPV vaccine included lack of physical activity in the
      past month (P = 0.002), past year use of complementary or alternative therapies
      (P = 0.021), and no history of smoking (P = 0.005). These results suggest that
      behavioral health factors may be associated with vaccine acceptability and
      further our understanding of how behavioral patterns may contribute to the uptake
      of new cancer prevention strategies.

PMID- 20142235
TI  - Aldehyde dehydrogenase 1 A1-positive cell population is enriched in tumor
      initiating cells and associated with progression of bladder cancer.
AB  - Aldehyde dehydrogenase 1 A1 (ALDH1A1) has recently been suggested as a marker for
      cancer stem or stem-like cancer cells of some human malignancies. The purpose of
      this study was to investigate the stem cell-related function and clinical
      significance of the ALDH1A1 in bladder urothelial cell carcinoma. Aldefluor assay
      was used to isolate ALDH1A1+ cells from bladder cancer cells. Stem cell
      characteristics of the ALDH1A1+ cells were then investigated by in vitro and in
      vivo approaches. Immunohistochemistry was done for evaluating ALDH1A1 expression
      on 22 normal bladder tissues and 216 bladder tumor specimens of different stage
      and grade. The ALDH1A1+ cancer cells displayed higher in vitro tumorigenicity
      compared with isogenic ALDH1A1- cells. The ALDH1A1+ cancer cells could generate
      xenograft tumors that resembled the histopathologic characteristics and
      heterogeneity of the parental cells. High ALDH1A1 expression was found in 26% (56
      of 216) of human bladder tumor specimens and significantly related to advanced
      pathologic stage, high histologic grade, recurrence and progression, and
      metastasis of bladder urothelial cell carcinomas (all P < 0.05). Furthermore,
      ALDH1A1 expression was inversely associated with cancer-specific and overall
      survivals of the patients (P = 0.027 and 0.030, respectively). Therefore,
      ALDH1A1+ cell population could be enriched in tumor-initiating cells. ALDH1A1 may
      serve as a useful marker for monitoring the progression of bladder tumor and
      identifying bladder cancer patients with poor prognosis who might benefit from
      adjuvant and effective treatments.

PMID- 20142236
TI  - 210Pb: a predictive biomarker of retrospective cigarette smoke exposure.
AB  - Although cigarette smoking continues to occur worldwide, there are few methods
      available to assess a person's retrospective exposure to mainstream smoke. The
      tobacco of cigarettes contains trace quantities of radioactive 210Pb and 210Po,
      which are volatilized and inhaled when a cigarette is smoked. It was hypothesized
      that urinary 210Pb and 210Po activity concentrations could be used as biomarkers
      of exposure to mainstream tobacco smoke. Human subjects (n = 250) were recruited
      from Beijing, China, and reported their smoking habits. Each subject provided a
      24-hour urine sample, which was assayed for its 210Pb and 210Po activity
      concentrations. Although the urinary 210Po activity from smoking was very low
      compared with background levels, the urinary 210Pb activity correlated with the
      number of cigarettes smoked per day (CPD; rho = 0.38, P < 0.001) and the urinary
      cotinine concentration (rho = 0.52, P < 0.001). In a linear regression model, a 1
      unit increase in CPD was associated with an increase of 0.13 mBq in urinary 210Pb
      activity. In a logistic regression model, a 1-unit increase in urinary 210Pb
      activity was associated with an estimated 25% increase in the odds of being a
      smoker. These data were modeled using the respiratory, gastrointestinal, and
      biokinetic models of the International Commission on Radiological Protection.
      When the final model was applied for a long-term smoker (20 CPD) that suddenly
      quits, the predicted urinary activity decreased to 50% of the steady-state
      activity in about 90 days. Based on this half-time estimate and the regression
      results, urinary 210Pb can be used to assess the probability of having smoked in
      the past months.

PMID- 20142237
TI  - Altered expression of apoptosis biomarkers in human colorectal microadenomas.
AB  - Human colorectal microadenomas are considered the earliest detectable
      premalignant lesions in the colon. They can be identified as aggregates of
      enlarged crypts with thicker epithelial linings and elongated luminal openings on
      the colonic mucosal surface after methylene blue staining and observation under a
      dissecting microscope. Multiple lines of evidence suggest that a central role in
      neoplastic development is played by the inhibition of apoptosis, followed by
      disruption of DNA repair. Understanding the early mechanisms of colorectal
      carcinogenesis may help develop new approaches of colorectal cancer prevention
      and treatment. The aim of the present study was to quantify poly-ADP ribose
      polymerase 1 (PARP-1)-positive cells and to evaluate apoptotic control mechanisms
      through Caspase-3 active and Bcl-2 protein expression in human microadenomas and
      in normal colorectal mucosa using immunofluorescence techniques coupled with
      confocal microscopy and immunoblot experiments. The mean percentage of PARP-1
      positive epithelial cells was 3.0 +/- 0.37% (SD) and 15.67 +/- 0.40% in
      microadenoma and in normal mucosa, respectively. Proteins involved in programmed
      cell death were differently expressed in microadenoma and in normal mucosa.
      Indeed, by semiquantitative immunofluorescence analysis, confirmed by Western
      blot, microadenoma showed low levels of Caspase-3 active and high levels of Bcl-2
      expression, whereas the opposite was true for normal colorectal mucosa
      [corrected]. In the stroma of normal colorectal mucosa, fibroblast-like cells and
      neutrophils were the cells that underwent apoptosis to a greater extent. In
      conclusion, malfunction of the control mechanisms of programmed cell death seems
      present in the early stages of colorectal cancer development.

PMID- 20142238
TI  - One size does not fit all: differences in HPV knowledge between Haitian and
      African American women.
AB  - BACKGROUND: Historically, all black persons, regardless of ancestry or country of
      origin, have been categorized as one group for cancer research and control
      efforts. This practice likely masks variability in exposure to determinants of
      disease, as well as in risk of cancer incidence and mortality. The current study
      examines potential differences in knowledge of human papilloma virus (HPV)
      between Haitian women living in Little Haiti, Miami, Florida, and a national
      sample of predominately African American women. METHODS: Data for Haitian women
      were collected in 2007 as part of an ongoing community-based participatory
      research initiative in Little Haiti. For purposes of comparison, we used data
      from a largely African American subsample of the 2007 Health Information National
      Trends Survey (HINTS). These data sources used identical items to assess HPV
      knowledge, providing a unique opportunity to examine how this outcome may vary
      between two very distinct populations who are often grouped together for research
      and disease surveillance. RESULTS: Relative to the HINTS sample, Haitian women
      were far less likely to have heard about HPV. CONCLUSIONS: Study data highlight
      important differences in Haitian and African American women's knowledge of HPV, a
      known determinant of cervical cancer risk. Such findings suggest that continuing
      to classify persons of similar phenotype but different cultural backgrounds and
      lifetime exposures as one group may preclude opportunity to understand, as well
      as attenuate, health disparity.

PMID- 20142239
TI  - Low proportion of false-negative smears in the Finnish program for cervical
      cancer screening.
AB  - BACKGROUND: We assessed the performance and validity of cytology in the Finnish
      screening program by considering high-grade neoplasia and cervical cancer (CIN3+)
      rates as detected in the program and by reevaluating cases observed after a
      negative screening test. METHODS: This retrospective study included 915 screen
      detected CIN3+ cases and 421 cases observed after a negative screen. Randomized
      and blinded reevaluation of potential false-negative screening tests covered 345
      archival case smears from women without a referral to colposcopy, as well as 689
      control smears for estimating performance and validity measures. RESULTS: The
      false-negative rate at the cutoff of low-grade squamous intraepithelial lesion or
      worse was 35% (95% confidence interval, 30-40%). In the subpopulation with
      original screening result of Pap I, the false-negative rate was 23% (18-28%).
      Sensitivity of screening laboratory rereading for detecting low-grade lesions or
      worse as atypical was 75% (67-82%) and specificity 93% (91-94%). Reproducibility
      of specific cytologic diagnoses was only fair. False negatives constituted 11% of
      all CIN3+ diagnoses in the screened population; those false negatives with an
      original Pap I screening result constituted 5%. CONCLUSIONS: Although screen
      failures in the form of diagnostic false negatives occur within the Finnish
      screening program, their effect on cancer incidence is fairly small and cannot be
      readily decreased without sacrificing the high specificity of screening or
      without high incremental costs. Feedback for the screening laboratories is
      needed, however, to improve the reproducibility of cytologic diagnoses to
      optimize the burden of intensified follow-up and treatment of precancerous
      lesions.

PMID- 20142240
TI  - Screen-film mammographic density and breast cancer risk: a comparison of the
      volumetric standard mammogram form and the interactive threshold measurement
      methods.
AB  - BACKGROUND: Mammographic density is a strong risk factor for breast cancer,
      usually measured by an area-based threshold method that dichotomizes the breast
      area on a mammogram into dense and nondense regions. Volumetric methods of breast
      density measurement, such as the fully automated standard mammogram form (SMF)
      method that estimates the volume of dense and total breast tissue, may provide a
      more accurate density measurement and improve risk prediction. METHODS: In 2000
      2003, a case-control study was conducted of 367 newly confirmed breast cancer
      cases and 661 age-matched breast cancer-free controls who underwent screen-film
      mammography at several centers in Toronto, Canada. Conditional logistic
      regression was used to estimate odds ratios of breast cancer associated with
      categories of mammographic density, measured with both the threshold and the SMF
      (version 2.2beta) methods, adjusting for breast cancer risk factors. RESULTS:
      Median percent density was higher in cases than in controls for the threshold
      method (31% versus 27%) but not for the SMF method. Higher correlations were
      observed between SMF and threshold measurements for breast volume/area (Spearman
      correlation coefficient = 0.95) than for percent density (0.68) or for absolute
      density (0.36). After adjustment for breast cancer risk factors, odds ratios of
      breast cancer in the highest compared with the lowest quintile of percent density
      were 2.19 (95% confidence interval, 1.28-3.72; P(t) <0.01) for the threshold
      method and 1.27 (95% confidence interval, 0.79-2.04; Pt = 0.32) for the SMF
      method. CONCLUSION: Threshold percent density is a stronger predictor of breast
      cancer risk than the SMF version 2.2beta method in digitized images.

PMID- 20142241
TI  - Nonsteroidal anti-inflammatory drugs and risk for ovarian and endometrial cancers
      in the Iowa Women's Health Study.
AB  - BACKGROUND: Several epidemiologic studies have shown inverse associations between
      use of nonsteroidal anti-inflammatory drugs (NSAID) and incident ovarian cancer,
      but the results are inconsistent. There have been only a few studies examining
      possible links between NSAIDs and endometrial cancer risk. We investigated
      associations between use of NSAIDs and incident ovarian and endometrial cancers
      in a prospective cohort of about 20,000 women with ages from 58 to 76 years in
      1992. Participants were asked how often they used aspirin and nonaspirin NSAIDs.
      Over 15 years, 311 endometrial and 167 ovarian incident malignancies were
      identified. Multivariate-adjusted hazard ratios were estimated using Cox
      proportional regression. RESULTS: Compared with women who reported no use of
      aspirin, the relative risks for ovarian cancer for those who used aspirin <2, 2
      to 5 times, and > or = 6 times per week were 0.83, 0.77, and 0.61, respectively
      (P trend = 0.04). We did not observe any association between nonaspirin NSAIDs
      use and ovarian cancer risk. Neither did we find associations between aspirin or
      nonaspirin NSAIDs use and risk for endometrial cancer. CONCLUSIONS: Our results
      suggest a possible inverse association between frequency of aspirin use and risk
      for ovarian cancer.

PMID- 20142242
TI  - Prevalence of tamoxifen use for breast cancer chemoprevention among U.S. women.
AB  - BACKGROUND: Tamoxifen can reduce the risk of developing invasive estrogen
      receptor-positive breast cancer by 49%, but it is unknown how many women in the
      United States are taking tamoxifen for primary prevention of breast cancer.
      METHODS: Data from the years 2000 and 2005 National Health Interview Surveys were
      analyzed to estimate the prevalence of tamoxifen use among U.S. women for primary
      chemoprevention of breast cancer. RESULTS: In 2000, approximately 0.2% of U.S.
      women ages 40 to 79 years without a personal history of breast cancer took
      tamoxifen for chemoprevention (95% confidence interval, 0.13-0.31). In 2005, the
      prevalence was approximately 0.08% (95% confidence interval, 0.03-0.17).
      CONCLUSION: The prevalence of tamoxifen use for primary prevention of breast
      cancer was very low in the years 2000 and 2005. Possible explanations for the low
      uptake are explored.

PMID- 20142244
TI  - Family history, mammographic density, and risk of breast cancer.
AB  - PURPOSE: Mammographic density is a strong and highly heritable risk factor for
      breast cancer. The purpose of this study was to examine the extent to which
      mammographic density explains the association of family history of breast cancer
      with risk of the disease. SUBJECTS AND METHODS: We carried out three nested case
      control studies in screening programs that included in total 2,322 subjects
      (1,164 cases and 1,158 controls). We estimated the independent and combined
      associations of family history and percent mammographic density at baseline with
      subsequent breast cancer risk. RESULTS: After adjustment for age and other risk
      factors, compared with women with no affected first-degree relatives, percent
      mammographic density was 3.1% greater for women with one affected first-degree
      relative, and 7.0% greater for women with two or more affected relatives (P =
      0.001 for linear trend across family history categories). The odds ratios for
      breast cancer risk were 1.37 [95% confidence interval (95% CI), 1.10-1.72] for
      having one affected relative, and 2.45 (95% CI, 1.30-4.62) for having two or more
      affected relatives (P for trend = 0.0002). Adjustment for percent mammographic
      density reduced these odds ratios by 16% and 14%, respectively. Percent
      mammographic density explained 14% (95% CI, 4-39%) of the association of family
      history (at least one affected first-degree relative) with breast cancer risk.
      CONCLUSIONS: Percent mammographic density has features of an intermediate marker
      for breast cancer, and some of the genes that explain variation in percent
      mammographic density might be associated with familial risk of breast cancer.

PMID- 20142243
TI  - Soft drink and juice consumption and risk of pancreatic cancer: the Singapore
      Chinese Health Study.
AB  - BACKGROUND: Sugar-sweetened carbonated beverages (called soft drinks) and juices,
      which have a high glycemic load relative to other foods and beverages, have been
      hypothesized as pancreatic cancer risk factors. However, data thus far are
      scarce, especially from non-European descent populations. We investigated whether
      higher consumption of soft drinks and juice increases the risk of pancreatic
      cancer in Chinese men and women. METHODS: A prospective cohort analysis was done
      to examine the association between soft drink and juice consumption and the risk
      of pancreatic cancer in 60,524 participants of the Singapore Chinese Health Study
      with up to 14 years of follow-up. Information on consumption of soft drinks,
      juice, and other dietary items, as well as lifestyle and environmental exposures,
      was collected through in-person interviews at recruitment. Pancreatic cancer
      cases and deaths were ascertained by record linkage of the cohort database with
      records of population-based Singapore Cancer Registry and the Singapore Registry
      of Births and Deaths. RESULTS: The first 14 years for the cohort resulted in
      cumulative 648,387 person-years and 140 incident pancreatic cancer cases.
      Individuals consuming > or = 2 soft drinks/wk experienced a statistically
      significant increased risk of pancreatic cancer (hazard ratio, 1.87; 95%
      confidence interval, 1.10-3.15) compared with individuals who did not consume
      soft drinks after adjustment for potential confounders. There was no
      statistically significant association between juice consumption and risk of
      pancreatic cancer. CONCLUSION: Regular consumption of soft drinks may play an
      independent role in the development of pancreatic cancer.

PMID- 20142245
TI  - Comparison of second cancer risks from brachytherapy and external beam therapy
      after uterine corpus cancer.
AB  - BACKGROUND: Adjuvant radiotherapy is common for uterine corpus cancer patients,
      yet the long-term carcinogenic effects of different types of radiotherapy have
      not been studied adequately. METHODS: Second primary cancer risks were quantified
      in a cohort of 60,949 individuals surviving > or = 1 year of uterine corpus
      cancer diagnosed from 1973 to 2003 in Surveillance, Epidemiology and End Results
      Program cancer registries. Incidence rate ratios (IRR) were estimated by
      comparing patients treated with surgery plus various types of radiotherapy with
      patients receiving surgery only. RESULTS: The IRRs of a second cancer were
      increased among irradiated patients compared with patients having surgery only
      [combination radiotherapy, IRR = 1.26; 95% confidence interval (CI), 1.16-1.36;
      external beam therapy, IRR = 1.15; 95% CI CI, 1.08-1.22; brachytherapy, IRR =
      1.07; 95% CI, 1.00-1.16]. IRRs were highest for heavily irradiated sites (that is
      colon, rectum, and bladder) and for leukemia following any external beam therapy,
      with the largest risks for solid cancers among 10-year survivors. Any external
      beam therapy had a 44% higher cancer risk at heavily irradiated sites than
      brachytherapy when the two treatments were directly compared (5-year survivors:
      IRR = 1.44; 95% CI, 1.19-1.75). We estimated that of 2,012 solid cancers
      developing > or = 5 years after irradiation, 213 (11%) could be explained by
      radiotherapy. CONCLUSIONS: Radiotherapy for uterine cancer increases the risk of
      leukemia and second solid cancers at sites in close proximity to the uterus,
      emphasizing the need for continued long-term surveillance for new malignancies.
      The overall risk of a second cancer was lower following brachytherapy compared
      with any external beam radiotherapy.

PMID- 20142246
TI  - Plasma levels of acid-labile subunit, free insulin-like growth factor-I, and
      prostate cancer risk: a prospective study.
AB  - BACKGROUND: The acid-labile subunit (ALS) acts in the insulin-like growth (IGF)
      system by binding circulating IGF-I in a ternary complex with binding protein
      (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier. Given the role
      of the IGF system in prostate cancer, ALS may influence carcinogenesis by
      modulating IGF-I levels or bioavailability. METHODS: We undertook a prospective
      study nested in the Physicians' Health Study to examine ALS, free IGF-I, and
      prostate cancer. We assayed circulating levels of ALS and IGF components among
      545 incident cases and 545 matched controls. We calculated relative risks (RR)
      and 95% confidence intervals (95% CI) adjusted for life-style factors, total IGF
      I, and IGFBP3. RESULTS: ALS was positively correlated with total IGF-I (r =
      0.58), IGFBP3 (r = 0.68), and free IGF-I (r = 0.36). Comparing highest versus
      lowest quartiles, we found no association between free IGF-I and prostate cancer
      risk (RR, 0.9; 95% CI, 0.6-1.3). In contrast, ALS was positively associated with
      risk among men in the 2nd (RR, 1.5; 94% CI, 1.0-2.3), 3rd (RR, 1.6; 94% CI, 1.1
      2.5), and 4th quartiles (RR, 1.4; 94% CI, 0.9-2.1) compared with lowest quartile.
      The association was stronger for advanced stage tumors (RR, 2.0; 94% CI, 0.8
      4.6). There was a suggestion of an interaction between ALS and total IGF-I,
      whereby high circulating IGF-I was associated with an increased risk of advanced
      prostate cancer among men with low but not higher ALS levels. DISCUSSION: Plasma
      ALS is positively associated with prostate cancer risk, and may interact
      biologically with IGF-I to affect carcinogenesis. These data provide further
      support for the role of the IGF axis in prostate cancer.

PMID- 20142247
TI  - Concurrent infection with multiple human papillomavirus types: pooled analysis of
      the IARC HPV Prevalence Surveys.
AB  - To understand viral interactions and the cross-reactivity of natural or vaccine
      induced responses, we investigated whether multiple human papillomavirus (HPV)
      infections, particularly certain combinations of types, have the tendency to
      cluster together. Cervical cell samples were collected from women in the
      framework of the IARC HPV Prevalence Surveys. Women with a cytology diagnosis of
      high-grade squamous intraepithelial lesion or worse were excluded, leaving 13,961
      women for this analysis. HPV DNA was assessed using a general GP5+/6+ primer
      mediated PCR. HPV genotyping was done using enzyme immunoassay or reverse line
      blot analysis. Logistic regression with type-specific HPV positivity as an
      outcome was used, adjusted for age, study area, and lifetime number of sexual
      partners. Woman-level random effects were added to represent unobservable risk
      factors common to all HPV types. The observed-to-expected ratio was 1.20 (95%
      credible interval, 1.14-1.26) for infection with two HPV types and 1.02 (95%
      credible interval, 0.91-1.12) for three for more types, with the best possible
      adjustment. Among combinations of specific HPV types, the tendency to cluster
      increased with the genetic similarity of the L1 region. High observed-to-expected
      ratios were found for closely homologous types, including HPV33/58, 18/45, 33/35,
      and 31/35. The excess of multiple infections, however, was clearly evident only
      when enzyme immunoassay, and not reverse line blot, was used as the genotyping
      method. The different results by genotyping method suggest that the apparent
      clustering of HPV infections was an artifact of the measurement process. Further
      investigation is required to evaluate other widely used HPV detection methods.

PMID- 20142248
TI  - Cumulative effect of multiple loci on genetic susceptibility to familial lung
      cancer.
AB  - BACKGROUND: Genetic factors play important roles in lung cancer susceptibility.
      In this study, we replicated the association of 5p15.33 and 6p21.33 with familial
      lung cancer. Taking into account the previously identified genetic susceptibility
      variants on 6q23-25/RGS17 and 15q24-25.1, we further determined the cumulative
      association of these four genetic regions and the population attributable risk
      percent of familial lung cancer they account for. METHODS: One hundred ninety
      four case patients and 219 cancer-free control subjects from the Genetic
      Epidemiology of Lung Cancer Consortium were used for the association analysis.
      Each familial case was chosen from one high-risk lung cancer family that has
      three or more affected members. Single nucleotide polymorphisms (SNP) on
      chromosomal regions 5p15.33, 6p21.33, 6q23-25/RGS17, and 15q24-25.1 were assessed
      for their associations with familial lung cancer. The cumulative association of
      the four chromosomal regions with familial lung cancer was evaluated with the use
      of a linear logistic model. Population attributable risk percent was calculated
      for each SNP using risk ratio. RESULTS: SNP rs31489 showed the strongest evidence
      of familial lung cancer association on 5p15.33 (P = 2 x 10(-4); odds ratio, 0.57;
      95% confidence interval, 0.42-0.77), whereas rs3117582 showed a weak association
      on 6p21.33 (P = 0.09; odds ratio, 1.47; 95% confidence interval, 0.94-2.31).
      Analysis of a combination of SNPs from the four regions provided a stronger
      cumulative association with familial lung cancer (P = 6.70 x 10(-6)) than any
      individual SNPs. The risk of lung cancer was increased to 3- to 11-fold among
      those subjects who had at least one copy of risk allele at each region compared
      with subjects without any of the risk factors. These four genetic regions
      contribute to a total of 34.6% of familial lung cancer in smokers. CONCLUSIONS:
      The SNPs in four chromosomal regions have a cumulative and significant
      association with familial lung cancer and account for about one-third of the
      population attributable risk for familial lung cancer.

PMID- 20142249
TI  - Associations between polymorphisms in glucuronidation and sulfation enzymes and
      mammographic breast density in premenopausal women in the United States.
AB  - OBJECTIVE: Sex hormones are metabolized to less active compounds via (a)
      glucuronidation catalyzed by UDP-glucuronosyltransferases (UGT) and (b) sulfation
      catalyzed by sulfotransferases (SULT). Functional UGT and SULT polymorphisms can
      affect clearance of sex hormones, thereby influencing exposure in hormone
      sensitive tissues, such as the breast. We assessed relationships between
      functional polymorphisms in the UGT and SULT genes and breast density in
      premenopausal women. METHODS: One hundred seventy-five women ages 40 to 45 years,
      who had a screening mammogram taken within the previous year, provided a genomic
      DNA sample. Mammograms were digitized to obtain breast density measures. Using
      generalized linear regression, we assessed associations between percent breast
      density and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1.
      RESULTS: Women with the SULT1A1(H213/H213) genotype had 16% lower percent breast
      density compared with women with the SULT1A1(R213/R213) genotype after
      controlling for ethnicity (P = 0.001). Breast density was 5% lower among women
      carrying at least one copy of the UGT1A1(TA7)-UGT1A3(R11)-UGT1A3(A47) haplotype
      compared with the UGT1A1(TA6)-UGT1A3(W11R)-UGT1A3(V47A) haplotype (P = 0.07). No
      associations were observed between polymorphisms in the UGT2B family or SULT1E1
      and breast density. CONCLUSION: Polymorphisms in SULT1A1 and the UGT1A locus may
      influence percent breast density in premenopausal women.

PMID- 20142250
TI  - Diabetes genes and prostate cancer in the Atherosclerosis Risk in Communities
      study.
AB  - There is a known inverse association between type 2 diabetes (T2D) and prostate
      cancer (PrCa) that is poorly understood. Genetic studies of the T2D-PrCa
      association may provide insight into the underlying mechanisms of this
      association. We evaluated associations in the Atherosclerosis Risk in Communities
      study between PrCa and nine T2D single nucleotide polymorphisms from genome-wide
      association studies of T2D (in CDKAL1, CDKN2A/B, FTO, HHEX, IGF2BP2, KCNJ11,
      PPARG, SLC30A8, and TCF7L2) and four T2D single nucleotide polymorphisms from pre
      genome-wide association studies (in ADRB2, CAPN10, SLC2A2, and UCP2). From 1987
      to 2000, there were 397 incident PrCa cases among 6,642 men ages 45 to 64 years
      at baseline. We used race-adjusted Cox proportional hazards models to estimate
      associations between PrCa and increasing number of T2D risk-raising alleles. PrCa
      was positively associated with the CAPN10 rs3792267 G allele [hazard ratio (HR)
      1.20; 95% confidence interval (CI), 1.00-1.44] and inversely associated with the
      SLC2A2 rs5400 Thr110 allele (HR, 0.85; 95% CI, 0.72, 1.00), the UCP2 rs660339
      Val55 allele (HR, 0.84; 95% CI, 0.73, 0.97) and the IGF2BP2 rs4402960 T allele
      (HR, 0.79; 95% CI, 0.61-1.02; blacks only). The TCF7L2 rs7903146 T allele was
      inversely associated with PrCa using a dominant genetic model (HR, 0.79; 95% CI,
      0.65-0.97). Further knowledge of T2D gene-PrCa mechanisms may improve
      understanding of PrCa etiology.

PMID- 20142251
TI  - Association of global levels of histone modifications with recurrence-free
      survival in stage IIB and III esophageal squamous cell carcinomas.
AB  - This study was aimed at understanding the effects of histone modifications on
      recurrence-free survival (RFS) after esophagectomy in esophageal squamous cell
      carcinoma (ESCC). The acetylation of histone H3 lysine (H3K9Ac), histone H3
      lysine 18 (H3K18Ac), and histone H4 lysine 12 (H4K12Ac), and the dimethylation of
      histone H3 lysine 9 (H3K9diMe) and histone H4 arginine 3 (H4R3diMe) were analyzed
      by immunohistochemistry in 237 ESCCs. The K-means clustering algorithm was used
      to identify unique patterns of histone modifications. At a median follow-up of
      5.1 years, 109 (46%) of 237 patients had developed recurrence of disease. Mean
      global levels of H3K9Ac, H3K18Ac, H3K9diMe, H4K12Ac, and H4R3diMe were 81.5%,
      65.1%, 80.3%, 45.9%, and 27.4%, respectively. In the analysis of individual
      histones, a 1% increase in the global level of H3K18Ac in pathologic stage III
      worsened RFS at 1.009 times [95% confidence interval (CI), 1.001-1.016; P =
      0.03], after adjusting for age, sex, and operative method. Cluster analysis also
      showed significant effects of histone modifications on RFS. For stage IIB
      cancers, Cox proportional hazards analysis showed that RFS of cluster 1, with
      high global levels of H3K18Ac and H4R3diMe, was 2.79 times poorer (95% CI, 1.14
      6.27; P = 0.008) than that of cluster 2, with low levels. RFS for stage III
      cancers was also poorer in cluster 1 than cluster 2 (adjusted hazard ratio, 2.42;
      95% CI, 1.10-5.34; P = 0.02). In conclusion, the present study suggests that
      global levels of histone modifications in ESCC may be an independent prognostic
      factor of RFS.

PMID- 20142254
TI  - Longer relative telomere length in blood from women with sporadic and familial
      breast cancer compared with healthy controls.
AB  - Telomeres cap the ends of chromosomes and are composed of a series of noncoding
      hexamer repeats. Telomeres protect the integrity of DNA coding sequences and are
      integral to the maintenance of genomic stability. Previous studies have shown an
      association between shortened lymphocyte telomeres and increased risk for
      specific cancers. However, the association between telomere length and breast
      cancer risk is less clear. We examined the relative telomere length (RTL) in
      blood from women with no personal or family history of cancer (controls) compared
      with different populations of women with breast cancer and women at high genetic
      risk for developing breast cancer. RTL was determined as the telomere to single
      gene copy number ratio assessed by quantitative PCR. Breast cancer cases (low
      risk, n = 40; high risk, n = 62) had significantly longer RTL compared with
      unaffected controls (n = 50; mean RTL = 1.11 versus 0.84; P < 0.0001). The
      assessment of risk by RTL quartile showed an increased risk for breast cancer
      with each longer quartile, with the most significant risk observed in the longest
      quartile (odds ratio, 23.3; confidence interval, 4.4-122.3; P < 0.0003). Women
      without breast cancer but at high risk due to family history (n = 30) also showed
      longer telomeres than controls (mean RTL = 1.09 versus 0.84; P < 0.0001). Our
      analysis supports previous findings of longer RTL in breast cancer cases compared
      with controls, and is the first to observe longer RTL in women without breast
      cancer identified as high risk based on family history.

PMID- 20142252
TI  - A systematic review of p53 as a prognostic factor of survival in squamous cell
      carcinoma of the four main anatomical subsites of the head and neck.
AB  - OBJECTIVES: To summarize existing evidence about whether the presence of mutant
      or upregulated p53 is a prognostic factor for patients presenting with squamous
      cell carcinoma arising from the larynx, oropharynx, hypopharynx, or oral cavity.
      METHOD: Relevant articles were identified using strict criteria for systematic
      searches. Associations between mutant or upregulated p53 versus wild-type or
      low/undetectable p53 in relation to overall survival and DFS were summarized by
      extracting or deriving hazard ratio (HR) estimates. Random-effects meta-analyses
      were used to account for between-study heterogeneity and to summarize the effect
      of p53 across studies. RESULTS: The meta-analyses gave a statistically
      significant pooled HR for overall survival in oral cavity [pooled HR, 1.48; 95%
      confidence interval, (95% CI), 1.03-2.11], and for disease-free survival in oral
      cavity (pooled HR, 1.47; 95% CI, 1.12-1.93) and in oropharynx (pooled HR, 0.45;
      95% CI, 0.27-0.73). Despite attempts to limit it, between-study heterogeneity was
      large in the majority of meta-analyses and the prognostic value of p53 was
      generally inconsistent and inconclusive across studies. CONCLUSION: The meta
      analysis results highlight that current evidence about the prognostic value of
      p53 in patients with squamous cell carcinoma of the head and neck is
      inconclusive. Large heterogeneity exists across studies in study-level and
      patient-level characteristics, making it difficult to ascertain a clear picture.
      Future studies are required in which p53 expression is investigated in a more
      standardized and biologically informative manner. In particular, prospectively
      planned individual patient data meta-analyses are needed to establish the
      prognostic importance of p53 for specific subgroups of patients undergoing
      specific treatments.

PMID- 20142253
TI  - Polymorphism in the GALNT1 gene and epithelial ovarian cancer in non-Hispanic
      white women: the Ovarian Cancer Association Consortium.
AB  - Aberrant glycosylation is a well-described hallmark of cancer. In a previous
      ovarian cancer case control study that examined polymorphisms in 26 glycosylation
      associated genes, we found strong statistical evidence (P = 0.00017) that women
      who inherited two copies of a single-nucleotide polymorphism in the UDP-N
      acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had
      decreased ovarian cancer risk. The current study attempted to replicate this
      observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped
      in 6,965 cases and 8,377 controls from 14 studies forming the Ovarian Cancer
      Association Consortium. The fixed effects estimate per rs17647532 allele was null
      (odds ratio, 0.99; 95% confidence interval, 0.92-1.07). When a recessive model
      was fit, the results were unchanged. Test for heterogeneity of the odds ratios
      revealed consistency across the 14 replication sites but significant differences
      compared with the original study population (P = 0.03). This study underscores
      the need for replication of putative findings in genetic association studies.

PMID- 20142255
TI  - Human papillomavirus types 16, 18, and 31 serostatus and prostate cancer risk in
      the Prostate Cancer Prevention Trial.
AB  - Since human papillomavirus (HPV) infection was first identified as a risk factor
      for cervical cancer, several seroepidemiologic and tissue-based studies have
      investigated HPV in relation to prostate cancer, another common genitourinary
      malignancy, with mixed results. To further inform this potential association, we
      conducted a large, prospective investigation of HPV types 16, 18, and 31 in
      relation to risk of prostate cancer in the Prostate Cancer Prevention Trial.
      Cases were a sample of men diagnosed with prostate cancer after visit 2 or on
      their end-of-study biopsy (n = 616). Controls were men not diagnosed with
      prostate cancer during the trial or on their end-of-study biopsy (n = 616).
      Controls were frequency matched to cases by age, treatment arm, and family
      history of prostate cancer. Sera from visit 2 were tested for IgG antibodies
      against HPV types 16, 18, and 31. No associations were observed for weak or
      strong HPV-16 [odds ratio (OR), 0.94; 95% confidence interval (95% CI), 0.53-1.64
      and OR, 1.07; 95% CI, 077-1.48, respectively], HPV-18 (OR, 0.75; 95% CI, 0.27
      2.04 and OR, 0.87; 95% CI, 0.47-1.63, respectively), or HPV-31 seropositivity
      (OR, 0.76; 95% CI, 0.45-1.28 and OR, 1.15; 95% CI, 0.80-1.64, respectively) and
      risk of prostate cancer. Considering this finding in the context of the HPV and
      prostate cancer literature, HPV does not appear to be associated with risk of
      prostate cancer, at least by mechanisms proposed to date, and using epidemiologic
      designs and laboratory techniques currently available.

PMID- 20142256
TI  - Colorectal cancer susceptibility quantitative trait loci in mice as a novel
      approach to detect low-penetrance variants in humans: a two-stage case-control
      study.
AB  - Thirty-five percent of colorectal cancer (CRC) susceptibility is thought to be
      attributable to genetics, but only a small proportion of the cases (<6%) can be
      explained by highly penetrant mutations. The rest of the susceptibility could be
      explained by a number of low-penetrance variants following a polygenic model of
      inheritance. Genetic modeling in rodents has been a successful tool for the
      unraveling of the genetic basis of diseases. The investigation of mouse
      quantitative trait loci led to the discovery of 15 "susceptibility to colorectal
      cancer" (Scc) loci. Thus, we aimed to analyze the human-mouse syntenic regions
      defined by these Scc loci and select human candidate genes within. Twenty-one
      genes were chosen and their single-nucleotide polymorphisms were tested as
      possible low-penetrance variants predisposing to CRC risk. Our most strongly
      associated single-nucleotide polymorphism, rs954353, seems to be in the 5' region
      of the CYR61 gene, which could implicate it in terms of the cis-regulation of the
      gene. CYR61 has been proposed as a connection point among signaling pathways and
      a probable marker for early CRC detection. However, we could not replicate the
      association. Despite our negative results, we believe that our candidate gene
      selection strategy could be quite useful in the future determination of variants
      predisposing to disease.

PMID- 20142257
TI  - Controversies in communication of genetic screening results for cancer: a report
      from the American Society of Preventive Oncology's Screening Special Interest
      Group (ASPO's 33rd Annual Meeting, March 8 to 10, 2009, Tampa, Florida).

PMID- 20142258
TI  - Comparative analyses of seven algorithms for copy number variant identification
      from single nucleotide polymorphism arrays.
AB  - Determination of copy number variants (CNVs) inferred in genome wide single
      nucleotide polymorphism arrays has shown increasing utility in genetic variant
      disease associations. Several CNV detection methods are available, but
      differences in CNV call thresholds and characteristics exist. We evaluated the
      relative performance of seven methods: circular binary segmentation, CNVFinder,
      cnvPartition, gain and loss of DNA, Nexus algorithms, PennCNV and QuantiSNP.
      Tested data included real and simulated Illumina HumHap 550 data from the
      Singapore cohort study of the risk factors for Myopia (SCORM) and simulated data
      from Affymetrix 6.0 and platform-independent distributions. The normalized
      singleton ratio (NSR) is proposed as a metric for parameter optimization before
      enacting full analysis. We used 10 SCORM samples for optimizing parameter
      settings for each method and then evaluated method performance at optimal
      parameters using 100 SCORM samples. The statistical power, false positive rates,
      and receiver operating characteristic (ROC) curve residuals were evaluated by
      simulation studies. Optimal parameters, as determined by NSR and ROC curve
      residuals, were consistent across datasets. QuantiSNP outperformed other methods
      based on ROC curve residuals over most datasets. Nexus Rank and SNPRank have low
      specificity and high power. Nexus Rank calls oversized CNVs. PennCNV detects one
      of the fewest numbers of CNVs.

PMID- 20142262
TI  - Window of opportunity: an episode of recruitment in a Banksia hybrid zone
      demonstrates continuing hybridization and phenotypic plasticity.
AB  - BACKGROUND AND AIMS: In perennial plants (especially post-fire resprouters),
      extant populations may reflect recruitment events in the distant past. This is
      true of hybrid zones formed by two Banksia species of swamps and woodlands in
      south-eastern Australia, Banksia robur and B. oblongifolia. Both resprout after
      fire but recruitment is dependent on periodic fires. Although plants of
      intermediate morphology have also been identified as hybrids using allozyme
      markers, the extent of ongoing hybridization is unknown. This study investigates
      whether both microsatellite markers and morphological measurements can be used to
      distinguish between the two species and their hybrids. A recent recruitment event
      and microsatellite markers allow the frequency of ongoing hybridization to be
      estimated, and also the effects of environmental variation on the morphology of
      plants and seedlings to be tested. METHODS: Variation at seven microsatellite
      loci was scored and seven leaf characteristics within putatively pure stands and
      mixed stands of both species were measured, revealing that the two species were
      genetically and morphologically distinct and that mixed stands also contained
      genetically and sometimes morphologically distinct hybrids. An opportunity
      created by wildfires was used to analyse the genetics and morphometrics of adults
      and seedlings from two hybrid zones. KEY RESULTS: Approximately 9 % of adults and
      21 % of seedlings were identified as genetic hybrids in both hybrid zones. Within
      these sites, the genotype of mature plants correlated well with morphology,
      except for some hybrid plants that had parental morphology. However, seedling
      morphology was highly variable and insufficient to describe the composition of
      the hybrid zone in this cohort. Greater phenotypic plasticity was evident among
      seedlings growing within the hybrid zones than seedlings growing in pots.
      CONCLUSIONS: The hybrid zones are complex and the range of genotypes detected in
      seedlings reveals both continuing hybridization and introgression.

PMID- 20142263
TI  - Structural colour and iridescence in plants: the poorly studied relations of
      pigment colour.
AB  - BACKGROUND: Colour is a consequence of the optical properties of an object and
      the visual system of the animal perceiving it. Colour is produced through
      chemical and structural means, but structural colour has been relatively poorly
      studied in plants. SCOPE: This Botanical Briefing describes the mechanisms by
      which structures can produce colour. In plants, as in animals, the most common
      mechanisms are multilayers and diffraction gratings. The functions of structural
      colour are then discussed. In animals, these colours act primarily as signals
      between members of the same species, although they can also play roles in
      camouflaging animals from their predators. In plants, multilayers are found
      predominantly in shade-plant leaves, suggesting a role either in photoprotection
      or in optimizing capture of photosynthetically active light. Diffraction gratings
      may be a surprisingly common feature of petals, and recent work has shown that
      they can be used by bees as cues to identify rewarding flowers. CONCLUSIONS:
      Structural colour may be surprisingly frequent in the plant kingdom, playing
      important roles alongside pigment colour. Much remains to be discovered about its
      distribution, development and function.

PMID- 20142264
TI  - European Surveillance of Antimicrobial Consumption (ESAC): outpatient systemic
      antimycotic and antifungal use in Europe.
AB  - OBJECTIVES: To assess the total outpatient systemic antimycotic and antifungal
      use in Europe, and to identify the antimycotic and antifungal substances most
      commonly used. METHODS: Within ESAC (www.esac.ua.ac.be), using the anatomical
      therapeutic chemical (ATC) and defined daily dose (DDD) classification, data on
      outpatient use of all 14 antimycotics (12) and antifungals (2) for systemic use
      (ATC J02 and D01B, respectively), aggregated at the level of the active
      substance, were collected for 2007. Use was expressed in DDD (WHO ATC/DDD,
      version 2008) per 1000 inhabitants per day (DID). Only countries for which data
      on both J02 and D01B use were available were included in the analysis. RESULTS:
      In 20 European countries (data for Cyprus and Estonia include hospital use),
      total outpatient systemic antimycotic and antifungal use varied by a factor of
      6.7 between the country with the highest (3.03 DID in Belgium) and the country
      with the lowest (0.45 in Croatia) use. Terbinafine, ketoconazole, itraconazole
      and fluconazole represented >94% of the total outpatient antimycotic and
      antifungal use in all countries. Terbinafine use represented >50% of the total
      systemic antimycotic and antifungal use in 16 out of 20 countries (not in
      Croatia, Italy, Luxembourg and Bulgaria). CONCLUSIONS: We present for the first
      time a standardized and validated data set of outpatient systemic antimycotic and
      antifungal use in Europe. Our study demonstrates a variation of antimycotic and
      antifungal use in Europe, as striking as that of antibiotic use. The ESAC data
      facilitate the auditing of antimycotic and antifungal prescribing, and the
      evaluation of the implementation of guidelines and public health policies to
      promote their judicious use.

PMID- 20142265
TI  - Comment on: Use of chlorhexidine-impregnated dressing to prevent vascular and
      epidural catheter colonization and infection: a meta-analysis.

PMID- 20142266
TI  - A survey of the identification and susceptibility testing of anaerobes in
      diagnostic microbiology laboratories in Scotland, UK.

PMID- 20142267
TI  - Postmenopausal hormone therapy and asthma onset in the E3N cohort.
AB  - BACKGROUND: Epidemiological studies have suggested that female hormones might
      play a role in asthma and that menopausal hormone therapy (MHT or hormone
      replacement therapy (HRT)) might increase the risk of asthma in postmenopausal
      women. The only prospective study addressing this issue reports an increase in
      the risk of developing asthma which was similar for oestrogen alone and
      oestrogen/progestagen treatment. METHODS: The association between the use of
      different types of MHT and the risk of asthma onset in postmenopausal women was
      investigated prospectively from 1990 to 2002 by biennial questionnaires as part
      of the French E3N cohort study. Asthma onset was considered to be the time of
      medical diagnosis of asthma cases occurring during the follow-up of women who
      were asthma free at baseline. Cox proportional hazards models were used,
      adjusting for potential confounding factors. RESULTS: Among 57 664 women free of
      asthma at menopause, 569 incident cases of asthma were identified during 495 448
      years of follow-up. MHT was related to an increased risk of asthma onset
      (HR=1.20, 95% CI 0.98 to 1.46) among recent users. The increase in risk of asthma
      onset was only significant among women reporting the use of oestrogen alone
      (HR=1.54, 95% CI 1.13 to 2.09) particularly in never smokers (HR=1.80, 95% CI
      1.15 to 2.80) and women reporting allergic disease prior to asthma onset
      (HR=1.86, 95% CI 1.18 to 2.93). A small increase in the risk of asthma onset
      associated with the use of oestrogen/progestagen was also observed in these
      subgroups. CONCLUSION: Postmenopausal use of oestrogen alone was associated with
      an increased rate of newly diagnosed asthma in menopausal women.

PMID- 20142268
TI  - Thrombin and trypsin directly activate vagal C-fibres in mouse lung via protease
      activated receptor-1.
AB  - The nature of protease-activated receptors (PARs) capable of activating
      respiratory vagal C-fibres in the mouse was investigated. Infusing thrombin or
      trypsin via the trachea strongly activated vagal lung C-fibres with action
      potential discharge, recorded with the extracellular electrode positioned in the
      vagal sensory ganglion. The intensity of activation was similar to that observed
      with the TRPV1 agonist, capsaicin. This was mimicked by the PAR1-activating
      peptide TFLLR-NH(2), whereas the PAR2-activating peptide SLIGRL-NH(2) was without
      effect. Patch clamp recording on cell bodies of capsaicin-sensitive neurons
      retrogradely labelled from the lungs revealed that TFLLR-NH(2) consistently
      evokes a large inward current. RT-PCR revealed all four PARs were expressed in
      the vagal ganglia. However, when RT-PCR was carried out on individual neurons
      retrogradely labelled from the lungs it was noted that TRPV1-positive neurons
      (presumed C-fibre neurons) expressed PAR1 and PAR3, whereas PAR2 and PAR4 were
      rarely expressed. The C-fibres in mouse lungs isolated from PAR1(-/-) animals
      responded normally to capsaicin, but failed to respond to trypsin, thrombin, or
      TFLLR-NH(2). These data show that the PAR most relevant for evoking action
      potential discharge in vagal C-fibres in mouse lungs is PAR1, and that this is a
      direct neuronal effect.

PMID- 20142270
TI  - Pain channelopathies.
AB  - Pain remains a major clinical challenge, severely afflicting around 6% of the
      population at any one time. Channelopathies that underlie monogenic human pain
      syndromes are of great clinical relevance, as cell surface ion channels are
      tractable drug targets. The recent discovery that loss-of-function mutations in
      the sodium channel Nav1.7 underlie a recessive pain-free state in otherwise
      normal people is particularly significant. Deletion of channel-encoding genes in
      mice has also provided insights into mammalian pain mechanisms. Ion channels
      expressed by immune system cells (e.g. P2X7) have been shown to play a pivotal
      role in changing pain thresholds, whilst channels involved in sensory
      transduction (e.g. TRPV1), the regulation of neuronal excitability (potassium
      channels), action potential propagation (sodium channels) and neurotransmitter
      release (calcium channels) have all been shown to be potentially selective
      analgesic drug targets in some animal pain models. Migraine and visceral pain
      have also been associated with voltage-gated ion channel mutations. Insights into
      such channelopathies thus provide us with a number of potential targets to
      control pain.

PMID- 20142269
TI  - In vivo long-term synaptic plasticity of glial cells.
AB  - Evidence showing the ability of glial cells to detect, respond to and modulate
      synaptic transmission and plasticity has contributed to the notion of glial cells
      as active synaptic partners. However, synaptically induced plasticity of glia
      themselves remains ill defined. Here we used the amphibian neuromuscular junction
      (NMJ) to study plasticity of perisynaptic Schwann cells (PSCs), glial cells at
      this synapse, following long-term in vivo modifications of synaptic activity. We
      used two models that altered synaptic activity in different manners. First,
      chronic blockade of postsynaptic nicotinic receptors using alpha-bungarotoxin
      (alpha-BTx) decreased facilitation, increased synaptic depression and decreased
      post-tetanic potentiation (PTP). Second, chronic nerve stimulation increased
      facilitation and resistance to synaptic depression, while leaving PTP unaltered.
      Our results indicate that there is no direct relationship between transmitter
      release and PSC calcium responses. Indeed, despite changes in transmitter release
      and plasticity in stimulated NMJs, nerve-evoked PSC calcium responses were
      similar to control. Similarly, PSC calcium responses in alpha-BTx treated NMJs
      were delayed and smaller in amplitude, even though basal level of transmitter
      release was increased. Also, when isolating purinergic and muscarinic components
      of PSC calcium responses, we found an increased sensitivity to ATP and a
      decreased sensitivity to muscarine in chronically stimulated NMJs. Conversely, in
      alpha-BTx treated NMJs, PSC sensitivity remained unaffected, but ATP- and
      muscarine-induced calcium responses were prolonged. Thus, our results reveal
      complex modifications of PSC properties, with differential modulation of
      signalling pathways that might underlie receptor regulation or changes in Ca(2+)
      handling. Importantly, similar to neurons, perisynaptic glial cells undergo
      plastic changes induced by altered synaptic activity.

PMID- 20142271
TI  - Select spinal lesions reveal multiple ascending pathways in the rat conveying
      input from the male genitalia.
AB  - The specific white matter location of all the spinal pathways conveying penile
      input to the rostral medulla is not known. Our previous studies using rats
      demonstrated the loss of low but not high threshold penile inputs to medullary
      reticular formation (MRF) neurons after acute and chronic dorsal column (DC)
      lesions of the T8 spinal cord and loss of all penile inputs after lesioning the
      dorsal three-fifths of the cord. In the present study, select T8 lesions were
      made and terminal electrophysiological recordings were performed 45-60 days later
      in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi
      pars alpha. Lesions included subtotal dorsal hemisections that spared only the
      lateral half of the dorsal portion of the lateral funiculus on one side, dorsal
      and over-dorsal hemisections, and subtotal transections that spared predominantly
      just the ventromedial white matter. Electrophysiological data for 448 single unit
      recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups
      based upon histological lesion reconstructions, revealed (1) ascending bilateral
      projections in the dorsal, dorsolateral and ventrolateral white matter of the
      spinal cord conveying information from the male external genitalia to MRF, and
      (2) ascending bilateral projections in the ventrolateral white matter conveying
      information from the pelvic visceral organs (bladder, descending colon, urethra)
      to MRF. Multiple spinal pathways from the penis to the MRF may correspond to
      different functions, including those processing affective/pleasure/motivational,
      nociception, and mating-specific (such as for erection and ejaculation) inputs.

PMID- 20142272
TI  - Autonomic control of heart rate by metabolically sensitive skeletal muscle
      afferents in humans.
AB  - Isolated activation of metabolically sensitive skeletal muscle afferents (muscle
      metaboreflex) using post-exercise ischaemia (PEI) following handgrip partially
      maintains exercise-induced increases in arterial blood pressure (BP) and muscle
      sympathetic nerve activity (SNA), while heart rate (HR) declines towards resting
      values. Although masking of metaboreflex-mediated increases in cardiac SNA by
      parasympathetic reactivation during PEI has been suggested, this has not been
      directly tested in humans. In nine male subjects (23 +/- 5 years) the muscle
      metaboreflex was activated by PEI following moderate (PEI-M) and high (PEI-H)
      intensity isometric handgrip performed at 25% and 40% maximum voluntary
      contraction, under control (no drug), parasympathetic blockade (glycopyrrolate)
      and beta-adrenergic blockade (metoprolol or propranalol) conditions, while beat
      to-beat HR and BP were continuously measured. During control PEI-M, HR was
      slightly elevated from rest (+3 +/- 2 beats min(-1)); however, this HR elevation
      was abolished with beta-adrenergic blockade (P < 0.05 vs. control) but augmented
      with parasympathetic blockade (+8 +/- 2 beats min(-1), P < 0.05 vs. control and
      beta-adrenergic blockade). The HR elevation during control PEI-H (+9 +/- 3 beats
      min(-1)) was greater than with PEI-M (P < 0.05), and was also attenuated with
      beta-adrenergic blockade (+4 +/- 2 beats min(-1), P < 0.05 vs. control), but was
      unchanged with parasympathetic blockade (+9 +/- 2 beats min(-1), P > 0.05 vs.
      control). BP was similarly increased from rest during PEI-M and further elevated
      during PEI-H (P < 0.05) in all conditions. Collectively, these findings suggest
      that the muscle metaboreflex increases cardiac SNA during PEI in humans; however,
      it requires a robust muscle metaboreflex activation to offset the influence of
      cardiac parasympathetic reactivation on heart rate.

PMID- 20142273
TI  - The first intestinal motility patterns in fetal mice are not mediated by neurons
      or interstitial cells of Cajal.
AB  - In mature animals, neurons and interstitial cells of Cajal (ICC) are essential
      for organized intestinal motility. We investigated motility patterns, and the
      roles of neurons and myenteric ICC (ICC-MP), in the duodenum and colon of
      developing mice in vitro. Spatiotemporal mapping revealed regular contractions
      that propagated in both directions from embryonic day (E)13.5 in the duodenum and
      E14.5 in the colon. The propagating contractions, which we termed ripples, were
      unaffected by tetrodotoxin and were present in the intestine of embryonic Ret
      null mutant mice, which lack enteric neurons. Neurally mediated motility patterns
      were first observed in the duodenum at E18.5. To examine the possible role of ICC
      MP, three approaches were used. First, intracellular recordings from the circular
      muscle of the duodenum did not detect slow wave activity at E16.5, but regular
      slow waves were observed in some preparations of E18.5 duodenum. Second,
      spatiotemporal mapping revealed ripples in the duodenum of E13.5 and E16.5 W/W(v)
      embryos, which lack KIT+ ICC-MP and slow waves. Third, KIT-immunoreactive cells
      with the morphology of ICC-MP were first observed at E18.5. Hence, ripples do not
      appear to be mediated by ICC-MP and must be myogenic. Ripples in the duodenum and
      colon were abolished by cobalt chloride (1 mm). The L-type Ca(2+) channel
      antagonist nicardipine (2.5 microm) abolished ripples in the duodenum and reduced
      their frequency and size in the colon. Our findings demonstrate that prominent
      propagating contractions (ripples) are present in the duodenum and colon of fetal
      mice. Ripples are not mediated by neurons or ICC-MP, but entry of extracellular
      Ca(2+) through L-type Ca(2+) channels is essential. Thus, during development of
      the intestine, the first motor patterns to develop are myogenic.

PMID- 20142274
TI  - Encoding of tangential torque in responses of tactile afferent fibres innervating
      the fingerpad of the monkey.
AB  - Torsional loads are ubiquitous during everyday dextrous manipulations. We
      examined how information about torque is provided to the sensorimotor control
      system by populations of tactile afferents. Torsional loads of different
      magnitudes were applied in clockwise and anticlockwise directions to a standard
      central site on the fingertip. Three different background levels of contact
      (grip) force were used. The median nerve was exposed in anaesthetized monkeys and
      single unit responses recorded from 66 slowly adapting type-I (SA-I) and 31 fast
      adapting type-I (FA-I) afferents innervating the distal segments of the
      fingertips. Most afferents were excited by torque but some were suppressed.
      Responses of the majority of both afferent types were scaled by torque magnitude
      applied in one or other direction, with the majority of FA-I afferent responses
      and about half of SA-I afferent responses scaled in both directions. Torque
      direction affected responses in both afferent types, but more so for the SA-I
      afferents. Latencies of the first spike in FA-I afferent responses depended on
      the parameters of the torque. We used a Parzen window classifier to assess the
      capacity of the SA-I and FA-I afferent populations to discriminate, concurrently
      and in real-time, the three stimulus parameters, namely background normal force,
      torque magnitude and direction. Despite the potentially confounding interactions
      between stimulus parameters, both the SA-I and the FA-I populations could extract
      torque magnitude accurately. The FA-I afferents signalled torque magnitude
      earlier than did the SA-I afferents, but torque direction was extracted more
      rapidly and more accurately by the SA-I afferent population.

PMID- 20142276
TI  - Web-based tools for quality assurance and radiation protection in diagnostic
      radiology.
AB  - Practical and philosophical aspects of radiation protection in diagnostic
      radiology have changed very little over the past 50 y even though patient doses
      have continued to rise significantly in this period. This rise has been driven by
      technological developments, such as multi-slice computed tomography, that have
      been able to improve diagnostic accuracy but not necessarily provide the same
      level of risk-benefit to all patients or groups of patients given the dose levels
      involved. Can practical radiation protection strategies hope to keep abreast of
      these ongoing developments? A project was started in 1992 in Liverpool that aimed
      to develop IT driven quality assurance (QA)/radiation protection software tools
      based upon a modular quality assurance dose data system. One of the modules
      involved the assessment of the patient entrance surface air kerma (ESAK) for an X
      ray examination that was based upon the use of calibrated X-ray tube exposure
      factors to calculate ESAK as well as collecting appropriate patient details (age,
      sex, weight, thickness etc). The package also contained modules for logging all
      necessary equipment performance QA data. This paper will outline the experience
      gained with this system through its transition from a local application on a
      stand alone PC within the department to the current web-based approach.
      Advantages of a web-based approach to delivering such an application as well as
      centrally storing data originating on many hospital sites will be discussed
      together with the scientific support processes that can be developed with such a
      system. This will include local, national and international considerations. The
      advantages of importing radiographic examination details directly from other
      electronic storage systems such as a hospital's radiology information system will
      be presented together with practical outcomes already achieved. This will include
      the application of statistical techniques to the very large data sets generated.
      The development of new examination QA performance indicators will be discussed.
      The application of web-based IT tools for QA and radiation protection in
      diagnostic radiology is already opening up the possibility of developing new and
      improved scientific support services as well as research possibilities in
      radiological informatics. These will be outlined together with areas for possible
      future development by the medical physics community.

PMID- 20142275
TI  - The TRPv1 receptor is a mediator of the exercise pressor reflex in rats.
AB  - The skeletal muscle exercise pressor reflex (EPR) induces increases in heart rate
      (HR) and mean arterial pressure (MAP) during physical activity. This reflex is
      activated during contraction by stimulation of afferent fibres responsive to
      mechanical distortion and/or the metabolic by-products of skeletal muscle work.
      The molecular mechanisms responsible for activating these afferent neurons have
      yet to be identified. It has been reported that activation of the transient
      receptor potential vanilloid 1 (TRPv1) receptor within skeletal muscle (localized
      to unmyelinated afferent fibres) elicits increases in MAP and HR similar to those
      generated by the EPR. Thus, we hypothesized that stimulation of the TRPv1
      receptor during muscle contraction contributes to the activation of the EPR. The
      EPR was activated by electrically induced static muscle contraction of the
      hindlimb in decerebrate Sprague-Dawley rats (n = 61) before and after the
      administration of the TRPv1 receptor antagonists, capsazepine (Capz; 100
      microg/100 microl), iodoresinaferatoxin (IRTX; 1 microg/100 microl), or Ruthenium
      Red (RR; 100 microg/100 microl). Static muscle contraction alone induced
      increases in both HR (8 +/- 2 bpm) and MAP (21 +/- 3 mmHg). The HR and MAP
      responses to contraction were significantly lower (P < 0.05) after the
      administration of Capz (2 +/- 1 bpm; 7 +/- 1 mmHg, respectively), IRTX (3 +/- 2
      bpm; 5 +/- 3 mmHg, respectively) and RR (0 +/- 1, bpm; 5 +/- 2 mmHg,
      respectively). These data suggest that the TRPv1 receptor contributes importantly
      to activation of the EPR during skeletal muscle contraction in the rat.

PMID- 20142277
TI  - Recently revised diagnostic reference levels in nuclear medicine in Bulgaria and
      in Finland.
AB  - An EU twinning project entitled 'Strengthening of administrative structures for
      radiation protection and safe use of ionising radiation in diagnostics and
      therapy' was established between Bulgaria and Finland, lasting from June 2008 to
      May 2009. One component of the project was to improve the optimisation of patient
      protection in nuclear medicine (NM) through revising diagnostic reference levels
      (DRLs). The revised DRLs are based on national surveys on the numbers of NM
      procedures and activities given to the patients in different procedures. The
      survey in Bulgaria was carried out in 2008 and that in Finland in 2007. National
      DRLs were established for the most frequent and dose-relevant examinations. The
      proposed DRLs in both countries are in good agreement with other national
      recommendations in Europe.

PMID- 20142278
TI  - Radiation protection in newer imaging technologies.
AB  - Not even a week passes without a paper getting published in peer reviewed
      journals on radiation protection in newer imaging technologies that either did
      not exist 10 y ago or were not established for routine use. Computed tomography
      (CT) happens to be a common element in most of these technologies. Radiation
      protection is high on the agenda of manufacturers and researchers and that is
      becoming a driving force for users and international organisations. The media and
      thus the public have their own share in increasing the momentum. The slice war
      seems to be shifting to dose war. Manufacturers are now chasing the target of sub
      mSv CT. The era of two digit mSv effective dose for a CT procedure is far from
      losing ground, although cardiac CT within 5 mSv seems possible. A few years ago
      the change in technology was faster than adoption of dose management but
      currently even the development of dose reduction techniques is faster than its
      adoption. There is dearth of large-scale surveys of practice and lack of surveys
      with change in technology.

PMID- 20142279
TI  - A "novel" intervention: a pilot study of children's literature and healthy
      lifestyles.
AB  - OBJECTIVE: To determine if reading an age-appropriate novel has the potential to
      improve BMI percentile and exercise- and nutrition-related knowledge and
      behaviors in girls aged 9 to 13 years who were enrolled in a childhood obesity
      treatment program. METHODS: This preliminary, randomized, controlled trial
      followed 81 obese girls aged 9 to 13 years who were enrolled in the Duke
      University Healthy Lifestyles Program, a comprehensive clinical and behavioral
      lifestyle-modification program for overweight and obese children. Thirty-one
      girls were randomly assigned to read the intervention novel, which describes an
      overweight girl who discovers improved health and self-efficacy, and 33
      participants were given a control novel to read. Participants were evaluated at
      the study intake and again at their scheduled follow-up appointments 1 to 2
      months later. Intake and follow-up BMI percentiles were evaluated for 17 girls in
      the program who did not receive either book. RESULTS: Follow-up data were
      available for 11 of 31 girls in the intervention-book group, 14 of 33 girls in
      the control-book group, and 14 of 17 girls who did not receive a book. There was
      a significantly greater reduction in BMI percentile among those in the
      intervention-book group (-0.71) versus those in the control-book group (-0.33; P
      = .03). Girls who read either book had a significantly greater reduction in BMI
      percentile (-0.49) than girls who were followed in the program but who were not
      assigned a book (0.05; P = .02). CONCLUSIONS: Age-appropriate fiction,
      particularly if it addresses health-oriented behaviors, shows potential for
      augmenting weight loss in girls who participate in a weight-management program.
      Future research is needed to determine if the novel is effective for healthy
      lifestyle promotion among all overweight and obese adolescents.

PMID- 20142280
TI  - Household routines and obesity in US preschool-aged children.
AB  - OBJECTIVE: To determine the association between the prevalence of obesity in
      preschool-aged children and exposure to 3 household routines: regularly eating
      the evening meal as a family, obtaining adequate sleep, and limiting screen
      viewing time. METHODS: We conducted a cross-sectional analysis of a nationally
      representative sample of approximately 8550 four-year-old US children who were
      assessed in 2005 in the Early Childhood Longitudinal Study, Birth Cohort. Height
      and weight were measured. We assessed the association of childhood obesity (BMI >
      or = 95th percentile) with 3 household routines: regularly eating the evening
      meal as a family (>5 nights per week); obtaining adequate nighttime sleep on
      weekdays (> or =10.5 hours per night); and having limited screen-viewing
      (television, video, digital video disk) time on weekdays (< or =2 hours/day).
      Analyses were adjusted for the child's race/ethnicity, maternal obesity, maternal
      education, household income, and living in a single-parent household. RESULTS:
      Eighteen percent of children were obese, 14.5% were exposed to all 3 routines,
      and 12.4% were exposed to none of the routines. The prevalence of obesity was
      14.3% (95% confidence interval [CI]: 11.3%-17.2%) among children exposed to all 3
      routines and 24.5% (95% CI: 20.1%-28.9%) among those exposed to none of the
      routines. After adjusting for covariates, the odds of obesity associated with
      exposure to all 3, any 2, or only 1 routine (compared with none) were 0.63 (95%
      CI: 0.46-0.87), 0.64 (95% CI: 0.47-0.85), and 0.84 (95% CI: 0.63-1.12),
      respectively. CONCLUSIONS: US preschool-aged children exposed to the 3 household
      routines of regularly eating the evening meal as a family, obtaining adequate
      nighttime sleep, and having limited screen-viewing time had an approximately 40%
      lower prevalence of obesity than those exposed to none of these routines. These
      household routines may be promising targets for obesity-prevention efforts in
      early childhood.

PMID- 20142281
TI  - Where perception meets reality: self-perception of weight in overweight
      adolescents.
AB  - OBJECTIVE: The goal of this study was to examine weight misperception among
      overweight adolescents in recent years and compare the demographic
      characteristics and weight-related behaviors of overweight adolescents who
      accurately and inaccurately perceive their weight status. METHODS: We used data
      from the nationally representative Youth Risk Behavior Surveillance System,
      collected every 2 years from 1999 through 2007. On the basis of self-reported
      height and weight, BMI percentile for age and sex was calculated. Overweight and
      obese respondents (BMI > or = 85th percentile) were classified into 2 groups: (1)
      misperceivers (weight perception "about right" or "underweight") or (2) accurate
      perceivers (weight perception "overweight"). We examined the proportion of
      misperceivers at each time point. Using the 2007 data, we compared demographic
      characteristics and weight-related behaviors of accurate perceivers and
      misperceivers with bivariate and multivariate analyses. RESULTS: Among overweight
      adolescents, the overall proportion of misperceivers ranged between 29% and 33%
      from 1999 through 2007. In 2007, 23% of overweight girls and 40% of overweight
      boys were misperceivers (P < .001). Both male and female accurate perceivers were
      significantly more likely than misperceivers to report trying to maintain or lose
      weight, exercising for weight control, and eating less for weight control.
      Adjusting for age, race/ethnicity, and BMI percentile, no significant differences
      in unhealthy weight-related behaviors were found between accurate perceivers and
      misperceivers in boys or girls. Male accurate perceivers were significantly less
      likely to report achieving recommended levels of fruit and vegetable intake and
      physical activity. CONCLUSIONS: Nearly 3 in 10 overweight adolescents do not
      consider themselves overweight. Those with an accurate weight perception reported
      some healthy weight-related behaviors but not higher levels of unhealthy weight
      related behaviors. With the substantial prevalence of weight misperception,
      clinicians should consider their patients' perceived weight status when pursuing
      patient-centered counseling of overweight adolescents.

PMID- 20142282
TI  - Pediatric uptake of a newly available antipsychotic medication.
AB  - OBJECTIVE: The uptake of new antipsychotic medications among children has not
      been studied adequately. Although ziprasidone received Food and Drug
      Administration approval for the treatment of psychotic disorders among children
      in June 2009, it first became available for off-label use by children in 2001 and
      presented an excellent case study for off-label market entry. The objective of
      this study was to determine the pattern of initiation and switching for off-label
      use of ziprasidone among Michigan children who were insured by Medicaid in the
      first year that ziprasidone was available. METHODS: We conducted a retrospective
      study by using Michigan Medicaid data for patients who were aged <21 years and
      had 2 years of continuous enrollment and at least 1 prescription for ziprasidone
      in the first year the medication was available. The main outcome measures were
      proportion of children prescribed ziprasidone as their first antipsychotic, with
      evidence of treatment resistance, and by a psychiatrist. RESULTS: In the first
      year, 292 individuals who met criteria were prescribed ziprasidone. Approximately
      53% had a diagnosis of psychosis. Explosive personality disorder and oppositional
      defiant disorder were the next most common diagnoses. For 33% of individuals,
      this was the first antipsychotic medication. Only 12% of individuals showed
      evidence of treatment resistance to other antipsychotic medications before
      switching to ziprasidone. CONCLUSIONS: During the period when ziprasidone had no
      approved pediatric usages, a small percentage of patients who were prescribed
      ziprasidone showed evidence of treatment resistance, the primary expected
      indication. Some prescribing for ziprasidone in the first year in this population
      could be considered inappropriate considering what was known about the safety and
      efficacy of ziprasidone in children and adolescents at the time. "Fail first" and
      prior authorization policies may be appropriate in the first year a medication is
      available so as to protect children from potential serious harm.

PMID- 20142283
TI  - Acute necrotizing encephalopathy in 3 brothers.
AB  - Acute necrotizing encephalopathy (ANE) is a devastating and rapidly progressive
      neurologic disorder that occurs in healthy children after common viral
      infections. Typically, ANE is sporadic and does not recur. However, familial
      (ANE1) and recurrent cases have been reported and were recently linked to
      mutations in RANBP2 (RAN-binding protein 2). We report here a multiply affected
      kindred with recurrent familial ANE. These affected male siblings (a set of twins
      and their older brother) all presented with prodromal fever and upper respiratory
      tract infection that progressed within 72 hours to seizures, coma, and ultimately
      death, a course that is typical of ANE. It should be noted that 1 brother was
      treated with early aggressive management, including corticosteroids, and he
      survived for an additional 5 years. This represents the second reported case of
      familial ANE in the United States and the only case of male siblings with
      consanguineous parents. We hope that early recognition and growing awareness can
      lead to more effective treatment and better outcomes in the future.

PMID- 20142284
TI  - Evaluation of growth in patients with isolated cleft lip and/or cleft palate.
AB  - OBJECTIVE: The purpose of the study was to evaluate the growth of patients with
      isolated cleft lip (CL), with or without cleft palate (CP), or CP during the
      first few years of life. METHODS: A retrospective analysis of data from birth to
      5 years for 307 patients with isolated CL/CP or CP alone who were seen in a large
      craniofacial center between 1980 and 2007 was performed. We analyzed growth
      patterns and feeding interventions. Anthropometric values were plotted onto 2000
      Centers for Disease Control and Prevention charts. Longitudinal analyses were
      performed to estimate age-related changes and to test whether feeding
      interventions or early education influenced age-related changes. RESULTS:
      Including progressive weight, length, and head circumference values, a total of
      1944 data points were available. The most frequent diagnosis was unilateral CL
      with CP (165 [53.7%] of 307 cases). No patients experienced significant failure
      to thrive during the study period, although predicted weight and length
      percentiles for age had initial decreases during the first year of life, with
      nadirs at 5.2 and 15 months, respectively. These decreases were followed by
      recovery that started at approximately 12 months for weight and at 20 months for
      length (P < .0001). Patients who had feeding interventions had a significantly (P
      = .047) increased gain rate over time for weight for length, compared with those
      who did not. CONCLUSIONS: In this population, there were weight and length
      decreases during the first year of life, which were not clinically significant
      and were followed by statistically significant recovery. Recovery seemed to be
      related to successful education and feeding interventions. Head circumference and
      weight for length started at lower percentiles but showed consistent gain over
      time.

PMID- 20142285
TI  - Interns overestimate the effectiveness of their hand-off communication.
AB  - OBJECTIVE: Theories from the psychology of communication may be applicable in
      understanding why hand-off communication is inherently problematic. The purpose
      of this study was to assess whether postcall pediatric interns can correctly
      estimate the patient care information and rationale received by on-call interns
      during hand-off communication. METHODS: Pediatric interns at the University of
      Chicago were interviewed about the hand-off. Postcall interns were asked to
      predict what on-call interns would report as the important pieces of information
      communicated during the hand-off about each patient, with accompanying rationale.
      Postcall interns also guessed on-call interns' rating of how well the hand-offs
      went. Then, on-call interns were asked to list the most important pieces of
      information for each patient that postcall interns communicated during the hand
      off, with accompanying rationale. On-call interns also rated how well the hand
      offs went. Interns had access to written hand-offs during the interviews.
      RESULTS: We conducted 52 interviews, which constituted 59% of eligible
      interviews. Seventy-two patients were discussed. The most important piece of
      information about a patient was not successfully communicated 60% of the time,
      despite the postcall intern's believing that it was communicated. Postcall and on
      call interns did not agree on the rationales provided for 60% of items. In
      addition, an item was more likely to be effectively communicated when it was a to
      do item (65%) or an item related to anticipatory guidance (69%) compared with a
      knowledge item (38%). Despite the lack of agreement on content and rationale of
      information communicated during hand-offs, peer ratings of hand-off quality were
      high. CONCLUSIONS: Pediatric interns overestimated the effectiveness of their
      hand-off communication. Theories from communication psychology suggest that
      miscommunication is caused by egocentric thought processes and a tendency for the
      speaker to overestimate the receiver's understanding. This study demonstrates
      that systematic causes of miscommunication may play a role in hand-off quality.

PMID- 20142286
TI  - Autoimmune hepatitis type 2 arising in PFAPA syndrome: coincidences or possible
      correlations?
AB  - PFAPA syndrome is a chronic disease classified in the group of autoinflammatory
      syndromes characterized by periodic fever, aphthous stomatitis, pharyngitis, and
      cervical adenitis in young children. The etiology of this disorder is still
      unknown, but a primary dysfunction of the innate immune system seems to be
      involved. According to Marshall criteria, it is not possible to diagnose PFAPA in
      the presence of autoimmune diseases. We present here the case report of an 8
      month girl with PFAPA who developed autoimmune hepatitis type 2 at the age of 18
      months. We suppose that the dysregulation in innate immunity that is typical of
      patients with PFAPA could trigger autoimmune disorders such as autoimmune
      hepatitis in susceptible subjects. The possible relationships between immune
      system dysfunction peculiar to this syndrome and autoimmune hepatitis are
      discussed.

PMID- 20142287
TI  - Childhood language skills and adult literacy: a 29-year follow-up study.
AB  - OBJECTIVE: Our aim was to assess the longitudinal trajectory of childhood
      receptive language skills and early influences on the course of language
      development. METHODS: Drawing on data collected for a nationally representative
      British birth cohort, the 1970 British Cohort Study, we examined the relationship
      between directly assessed early receptive language ability, family background,
      housing conditions, early literacy environment, and adult literacy skills. A
      sample of 11349 cohort members who completed the English Picture Vocabulary Test
      at 5 years of age were studied again at 34 years of age, when they completed a
      direct assessment of their basic literacy skills. We contrasted experiences of
      individuals with language problems at age 5 against the experiences of those with
      normal language skills at that age, assessing the role of socioeconomic family
      background and early literacy environment in influencing the longitudinal course
      of developmental language problems. Statistical comparisons of rates with chi(2)
      tests at P values of .001, .01, and .05 were made, as well as multivariate
      logistic regressions. RESULTS: Cohort members with receptive language problems at
      age 5 had a relatively disadvantaged home life in childhood, both in terms of
      socioeconomic resources and the education level of their parents, but also
      regarding their exposure to a stimulating early literacy environment. Although
      there is significant risk for poor adult literacy among children with early
      language problems, the majority of these children develop competent functional
      literacy levels by the age of 34. Factors that reduce the risk for persistent
      language problems include the child being born into a working family, parental
      education beyond minimum school-leaving age, advantageous housing conditions, and
      preschool attendance. CONCLUSION: Effective literacy-promoting interventions
      provided by pediatric primary care providers should target both children and
      parents.

PMID- 20142288
TI  - Shoulder injuries in US high school baseball and softball athletes, 2005-2008.
AB  - OBJECTIVE: The objective of this study was to determine factors that are involved
      in shoulder injury rates among high school athletes who participate in organized
      baseball and softball. METHODS: Baseball- and softball-related injury data were
      collected during the 2005-2008 academic years from approximately 74 nationally
      representative high schools via High School Reporting Information Online.
      RESULTS: Certified athletic trainers reported 91 baseball shoulder injuries and
      40 softball shoulder injuries during 528147 and 399522 athlete exposures,
      respectively. The injury rate was 1.72 injuries per 10000 athlete exposures for
      baseball and 1.00 injuries per 10000 athlete exposures for softball. Muscle
      strain/incomplete tears were the most common injuries in both baseball (30.8%)
      and softball (35.0%). In practices, throwing, not including pitching, caused more
      than half of softball injuries (68.2%) as compared with competition injuries
      (23.5%; injury proportion ratio [IPR]: 2.90 [95% confidence interval (CI): 1.17
      7.15]; P = .015), whereas pitching was the most common mechanism in causing
      shoulder injuries during baseball practice (41.9%) compared with competitions
      (25.6%; IPR: 1.64 [95% CI: 0.88-3.04]; P = .17). Eighty-one percent of the
      baseball shoulder injuries and 82.5% of the softball shoulder injuries were new.
      Ten percent of baseball athletes and 5.3% of softball athletes sustained injuries
      that required surgery (IPR: 1.40 [95% CI: 0.32-6.10]; P = .93). Injuries that
      were sustained while the athlete was on the pitcher's mound were significantly
      more likely to result in surgery than any other field position (IPR: 2.64 [95%
      CI: 1.65-4.21]; P = .0061). Injured baseball players were more than twice as
      likely to be pitchers. CONCLUSIONS: Although rates and patterns of shoulder
      injuries are similar between baseball and softball players, injury rates and
      patterns differ between field positions within each sport, as well as by injury
      severity and the athletes' year in school.

PMID- 20142289
TI  - Prevalence of food and beverage brands in movies: 1996-2005.
AB  - OBJECTIVE: The objective of this study was to describe food and beverage brand
      placements in a large representative sample of popular movies. METHODS: We
      identified and coded brand placements for foods, beverages, and food retail
      establishments in the top 20 US box office movie hits for each year from 1996 to
      2005. We also coded general movie characteristics (Motion Picture Association of
      America rating, run time, genre, and information about major characters). We
      summarized the number and types of food, beverage, and food retail establishment
      brands by movie characteristics and also identified manufacturers that are
      associated with each of the brands. RESULTS: Of the 200 movies coded, 138 (69%)
      contained at least 1 food, beverage, or food retail establishment brand. Movies
      rated PG-13 and R were significantly more likely to have brand placements
      compared with movies in other rating categories. Comedies, action/adventures, and
      horror films had more brand placements than other genres. We did not detect a
      significant difference in the number of movies with brand placements or mean
      number of placements per movie by year of movie release. A total of 1180 brand
      placements were identified and verified, including 427 food, 425 beverage, and
      328 food retail establishment brand placements. Candy/confections (26%) and salty
      snacks (21%) were the most prevalent food brands, sugar-sweetened beverages (76%)
      were the most prevalent beverage brands, and fast food composed two thirds of the
      food retail establishment brand placements. CONCLUSIONS: Food, beverage, and food
      retail establishment brands are frequently portrayed in movies, and most of the
      brand placements are for energy-dense, nutrient-poor foods or product lines.
      Movies are a potent source of advertising to children, which has been largely
      overlooked.

PMID- 20142290
TI  - Corneal abrasions in young infants.
AB  - OBJECTIVES: We sought to determine the prevalence of corneal abrasions and
      possible associations with fingernail length, demographic information, sleeping,
      and crying among young infants. METHODS: Parents of 1- to 12-week-old infants
      without symptoms who were presenting for well-child visits completed a brief
      questionnaire on age, gender, race, fingernail-trimming practices, and sleeping
      and crying in the preceding 24-hour period. Fingernail length was measured, and
      eyes were examined through staining with fluorescein and
      illumination/magnification with a Bluminator (Eidolon Optical, Natick, MA).
      Patients with corneal abrasions were given orally administered acetaminophen and
      erythromycin ointment. Masked interrater reliability for abrasions was measured.
      Logistic regression analyses determined the association of corneal abrasions with
      potential covariates. RESULTS: Ninety-six subjects were enrolled, including 47
      girls (49%), with a mean age of 32.2 days (SD: 21.7 days). Forty-seven infants
      (49%) had abrasions. Demographic variables and mean crying times (114.8 +/- 124.9
      vs 86.5 +/- 111.7 minutes; P < .24) were not significantly different for infants
      with and without abrasions. Infants with abrasions slept more (15.9 +/- 3.3 vs
      14.5 +/- 3.6 hours; P = .054). Associations of fingernail-trimming method and
      fingernail length with corneal abrasions were not statistically significant.
      Masked interrater reliability was high, with agreement between the primary
      investigator and the associate investigator for 20 (91%) of 22 eyes and agreement
      between the primary investigator and a pediatric ophthalmologist for 9 (90%) of
      10 eyes. CONCLUSIONS: Corneal abrasions are extremely common among 1- to 12-week
      old infants and have unclear clinical significance. Primary care physicians
      should be careful about attributing unexplained persistent crying to corneal
      abrasions, potentially missing a more-serious problem.

PMID- 20142291
TI  - Weight and age as predictors for passing the infant car seat challenge.
AB  - OBJECTIVE: The American Academy of Pediatrics recommends observation of preterm
      and at-risk infants in their car seat before hospital discharge to screen for
      breathing problems. This observation period, which we refer to as the infant car
      seat challenge (ICSC), is used to determine readiness for travel in a car seat.
      Infants who fail the ICSC are recommended to travel in a car bed. Limited data
      exist to identify risk factors for failing the ICSC, and no guidelines are
      available to facilitate transition from car beds to car seats. The purpose of
      this study was to determine whether weight and age are predictors for passing the
      ICSC. METHODS: This retrospective study evaluated 43 infants referred to the
      Children's Hospital Boston Center for Healthy Infant Lung Development for a
      repeat ICSC after initial failure and 37 infants who passed or failed their
      initial ICSC at the Caritas Saint Elizabeth's Medical Center. Gender, birth
      weight, gestational age (GA), weight (ICSC weight), corrected GA, and
      chronological age at time of ICSC were extracted, and logistic regression
      analysis was performed. RESULTS: The average GA at birth of infants referred was
      35 weeks 2 days (+/-2 weeks 3 days), and almost equal numbers of boys and girls
      were referred. A majority of infants passed their initial rechallenge (38 [88%]
      of 43). Infants who failed the repeat challenge were slightly smaller (3327 +/-
      927 vs 3913 +/- 936 g) and younger at time of retesting (CGA 40 weeks 5 days vs
      42 weeks 5 days; chronological age 39.2 vs 52.2 days). Neither weight nor age at
      initial or repeat ICSC predicted passing the ICSC. CONCLUSIONS: This study
      suggests that ICSC screenings remain the safest method for transitioning preterm
      infants from a car bed to a car seat.

PMID- 20142292
TI  - Variation in surgical management of vesicoureteral reflux: influence of hospital
      and patient factors.
AB  - OBJECTIVE: Controversy exists over surgical procedure choice for vesicoureteral
      reflux (VUR) in children. Either ureteral reimplantation (UR) or a newer
      procedure, endoscopic injection (EI), may be chosen; however, the factors that
      determine procedure choice for any individual patient are unclear. The objective
      of this study was to identify patient and hospital factors associated with the
      choice of EI for children undergoing antireflux surgery. PATIENTS AND METHODS: We
      searched the Pediatric Health Information System, a national database collected
      by freestanding children's hospitals. We identified children aged <18 years with
      primary VUR who underwent surgery (UR or EI) between 2003 and 2008. We used
      multivariate logistic regression models to evaluate whether the type of procedure
      performed was associated with hospital-level factors including individual
      hospital, hospital region, size, and teaching status, as well as patient features
      including age, race, gender, and insurance type. RESULTS: We identified 15026
      children with primary VUR who underwent antireflux surgery between 2003 and 2008.
      Of these, 3611 children (24%) were treated at hospitals that performed reimplant
      only. Among children treated at institutions offering both procedures, 5562 (49%)
      underwent injection and 5853 (51%) underwent reimplant. Patients who received EI
      were significantly older and more likely to be girls, white, and publicly insured
      than those who had UR. They were more likely to have been treated at hospitals
      that were larger, were teaching hospitals, or were located in larger metropolitan
      areas or the South rather than the Northeast. After adjusting for other
      covariates, the treating hospital was the most important factor predicting
      procedure choice. CONCLUSIONS: The hospital at which a patient receives treatment
      is the single most important feature that drove procedure choice for children
      with primary VUR. The patient's age, gender, insurance status, and disease
      severity played a smaller, although significant, role.

PMID- 20142293
TI  - A review of the effects of prenatal cocaine exposure among school-aged children.
AB  - CONTEXT: Studies through 6 years have shown no long-term direct effects of
      prenatal cocaine exposure (PCE) on children's physical growth, developmental test
      scores, or language outcomes. Little is known about the effects of PCE among
      school-aged children aged 6 years and older. OBJECTIVE: We reviewed articles from
      studies that examined the effects of PCE on growth, cognitive ability, academic
      functioning, and brain structure and function among school-aged children.
      METHODS: Articles were obtained by searching PubMed, Medline, TOXNET, and
      PsycInfo databases from January 1980 to December 2008 with the terms "prenatal
      cocaine exposure," "cocaine," "drug exposure," "substance exposure," "maternal
      drug use," "polysubstance," "children," "adolescent," "in utero," "pregnancy,"
      "development," and "behavior." Criteria for inclusion were (1) empirical research
      on children aged 6 years and older prenatally exposed to cocaine, (2) peer
      reviewed English-language journal, (3) comparison group, (4) longitudinal follow
      up or historical prospective design, (5) masked assessment, (6) exclusion of
      subjects with serious medical disabilities, and (7) studies that reported
      nonredundant findings for samples used in multiple investigations. Thirty-two
      unique studies met the criteria. Each article was independently abstracted by 2
      authors to obtain sample composition, methods of PCE assessment, study design,
      comparison groups, dependent variables, covariates, and results. RESULTS:
      Associations between PCE and growth, cognitive ability, academic achievement, and
      language functioning were small and attenuated by environmental variables. PCE
      had significant negative associations with sustained attention and behavioral
      self-regulation, even with covariate control. Although emerging evidence suggests
      PCE-related alterations in brain structure and function, interpretation is
      limited by methodologic inconsistencies. CONCLUSIONS: Consistent with findings
      among preschool-aged children, environmental variables play a key role in
      moderating and explaining the effects of PCE on school-aged children's
      functioning. After controlling for these effects, PCE-related impairments are
      reliably reported in sustained attention and behavioral self-regulation among
      school-aged children.

PMID- 20142294
TI  - Outcomes in children after intestinal transplant.
AB  - OBJECTIVE: The survival rates after pediatric intestinal transplant according to
      underlying disease are unknown. The objective of our study was to describe the
      population of pediatric patients receiving an intestinal transplant and to
      evaluate survival according to specific disease condition. PATIENTS: Pediatric
      patients (< or =21 years of age) with intestinal failure meeting criteria for
      intestinal transplant were included in the study. METHODS: A retrospective review
      of the United Network for Organ Sharing intestinal transplant database (January
      1, 1991, to May 16, 2008), including all pediatric transplant centers
      participating in the United Network for Organ Sharing, was conducted. The main
      outcome measures were survival and mortality. RESULTS: Eight hundred fifty-two
      children received an intestinal transplant (54% male). Median age and weight at
      the time of transplant were 1 year (interquartile rage: 1-5) and 10.7 kg
      (interquartile rage: 7.8-21.7). Sixty-nine percent of patients also received a
      simultaneous liver transplant. The most common diagnoses among patients who
      received a transplant were gastroschisis (24%), necrotizing enterocolitis (15%),
      volvulus (14%), other causes of short-gut syndrome (19%), functional bowel
      syndrome (16%), and Hirschsprung disease (7%). The Kaplan-Meier curves
      demonstrated variation in patient survival according to diagnosis. Cox regression
      analysis confirmed a survival difference according to diagnosis (P < .001) and
      demonstrated a survival advantage for those patients listed with a diagnosis of
      volvulus (P < .01) compared with the reference gastroschisis. After adjusting for
      gender, recipient weight, and concomitant liver transplant, children with
      volvulus had a lower hazard ratio for survival and a lower risk of mortality.
      CONCLUSIONS: Survival after intestinal transplant was associated with the
      underlying disease state. The explanation for these findings requires additional
      investigation into the differences in characteristics of the population of
      children with intestinal failure.

PMID- 20142295
TI  - Effect of needle length when immunizing obese adolescents with hepatitis B
      vaccine.
AB  - OBJECTIVE: Several studies have noted that obese adolescents and adults achieve
      lower titers of antibody in response to vaccines such as hepatitis B virus (HBV)
      vaccine. The objective of this study was to determine whether use of a longer
      (1.5-in) rather than a standard (1-in) needle to penetrate the thicker deltoid
      fat pad among obese youth would result in higher antibody titers after
      immunization against HBV. METHODS: Obese adolescents from a large metropolitan
      area who had not previously received the HBV vaccine were randomly assigned to be
      immunized with HBV vaccine by using either a 1-inch or a 1.5-inch needle.
      RESULTS: Those who were immunized with a 1.5-inch needle achieved significantly
      higher antibody titers to hepatitis B surface antigen (median titers: 1-inch =
      189.8 mIU/mL, 1.5-inch = 345.4 mIU/mL; P = .03). CONCLUSIONS: This finding
      supports the hypothesis that needle length accounts for a significant portion of
      the discrepancy in immune response to HBV vaccine that is seen among those with
      obesity.

PMID- 20142297
TI  - Decreased GABAA and GABAB receptor functional activity in cannabinoid CB1
      receptor knockout mice.
AB  - The interaction between brain GABAergic and endocannabinoid systems was evaluated
      by examining the quantitative and functional status of GABAergic receptors in
      cannabinoid CB(1) receptor knockout (CB(1)(-/-)) mice. To this aim, GABA(A)
      ([(3)H]-Muscimol binding assay), GABA(B) (baclofen-stimulated [(35)S]-GTPgammaS
      binding assay), GABA(A)alpha(1), GABA(A)alpha(2) and GABA(A)gamma(2) receptors
      gene expression (real-time reverse transcriptase polymerase chain reaction [PCR])
      were carried out in CB(1)(-/-) and wild-type mice (CB(1)(+/+)). [(3)H]-Muscimol
      binding assays revealed significant reduction in the density of GABA(A) receptors
      in CA2 (30%) and DG (28%) of the hippocampus, thalamus (40%), cingulate (28%) and
      motor cortex (35%) of CB(1)(-/-) mice. Functional activity of metabotropic
      GABA(B) receptors was measured by evaluating the ability of GABA(B) agonist
      baclofen to stimulate [(35)S]-GTPgammaS binding. The results showed significant
      reduced [(35)S]-GTPgammaS binding in CA1 (61%), CA3 (51%) and DG (60%) of CB(1)(
      /-) mice compared with CB(1)(+/+) mice. Real-time reverse transcriptase PCR was
      carried out for evaluating gene expression of alpha(1), alpha(2) and gamma(2)
      subunits of GABA(A) receptor in the amygdala. The results showed significant
      reduced GABA(A)alpha(1) (50%) and GABA(A)alpha(2) (40%) receptor subunits gene
      expression in the amygdala of CB(1)(-/-) mice. No difference was observed in
      GABA(A)gamma(2) receptor subunit gene expression. This study provides strong
      evidence of the involvement of CB(1) receptors in the control of GABAergic
      responses mediated by GABA(A) and GABA(B) receptors, and suggests a possible role
      of the endocannabinoid system in the regulation of anxiety-related disorders.

PMID- 20142296
TI  - Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic
      background.
AB  - To investigate the role of HLA-DQ2 in the pathogenesis of associated immune
      disorders, we generated transgenic mice that expressed HLA-DQ2 in the absence of
      endogenous murine class II molecules (AE(0)DQ2). These AE(0)DQ2 mice with a mixed
      genetic background spontaneously developed skin lesions on their ears, whereas
      control AE(0)DQ6 genotype control mice (also with a mixed genetic background) did
      not. The skin lesions were characterized by deep subepidermal blistering with
      hydropic degeneration and lymphoid infiltration in the subepidermal area as
      determined by histopathology. Immunofluorescence analysis revealed thick band
      like granular deposition of IgG, IgM, and a thin band of IgA deposition along the
      basement membrane. AE(0)DQ2 mice also developed significant and progressive
      hematuria and proteinuria as compared with the AE(0)DQ6 mice (p < 0.05).
      Histopathology showed immune complex deposits in the glomeruli of AE(0)DQ2 mice.
      Immunofluorescence analysis showed progressive mesangial and capillary wall
      deposition of IgA, IgM, IgG and C1q in the kidney. With electron microscopy, the
      deposits showed a 'fingerprint' substructure; and tubuloreticular structures were
      identified within endothelial cells. Conversely, these changes were not observed
      in AE(0)DQ6 mice. Serum anti-double stranded (ds)DNA IgM and IgG levels were also
      significantly elevated among AE(0)DQ2 mice compared with AE(0)DQ6 mice (p <
      0.001). In conclusion, AE(0)DQ2 mice spontaneously develop an autoimmune lupus
      like syndrome and are useful model for this disease. It remains to be determined
      whether genetic admixture played a role in the development of this systemic lupus
      erythematosus-like syndrome in HLA-DQ2 transgenic mice. Lupus (2010) 19, 815-829.

PMID- 20142298
TI  - Proteomic research in psychiatry.
AB  - Psychiatric disorders such as Alzheimer's disease, schizophrenia and mood
      disorders are severe and disabling conditions of largely unknown origin and
      poorly understood pathophysiology. An accurate diagnosis and treatment of these
      disorders is often complicated by their aetiological and clinical heterogeneity.
      In recent years proteomic technologies based on mass spectrometry have been
      increasingly used, especially in the search for diagnostic and prognostic
      biomarkers in neuropsychiatric disorders. Proteomics enable an automated high
      throughput protein determination revealing expression levels, post-translational
      modifications and complex protein-interaction networks. In contrast to other
      methods such as molecular genetics, proteomics provide the opportunity to
      determine modifications at the protein level thereby possibly being more closely
      related to pathophysiological processes underlying the clinical phenomenology of
      specific psychiatric conditions. In this article we review the theoretical
      background of proteomics and its most commonly utilized techniques. Furthermore
      the current impact of proteomic research on diverse psychiatric diseases, such as
      Alzheimer's disease, schizophrenia, mood and anxiety disorders, drug abuse and
      autism, is discussed. Proteomic methods are expected to gain crucial significance
      in psychiatric research and neuropharmacology over the coming decade.

PMID- 20142299
TI  - Effects of a Rhodiola rosea L. extract on acquisition and expression of morphine
      tolerance and dependence in mice.
AB  - This study investigated the effect of Rhodiola rosea L. extract on acquisition
      and expression of morphine tolerance and dependence in mice. Therefore animals
      were injected with repeated administration of morphine (10 mg/kg, subcutaneous)
      twice daily for five or six days, in order to make them tolerant or dependent.
      Rhodiola rosea L. extract (0, 10, 15 and 20 mg/kg) was administered by the
      intragastric route 60 min prior to each morphine injection (for acquisition) or
      prior the last injection of morphine or naloxone on test day (for tolerance or
      dependence expression, respectively). Morphine tolerance was evaluated by testing
      its analgesic effect in the tail flick test at the 1st and 5th days. Morphine
      dependence was evaluated by counting the number of withdrawal signs (jumping,
      rearing, forepaw tremor, teeth chatter) after naloxone injection (5 mg/kg;
      intraperitoneal) on the test day (day 6). Results showed that Rhodiola rosea L.
      extract significantly reduced the expression of morphine tolerance, while it was
      ineffective in modulating its acquisition. Conversely, Rhodiola rosea L. extract
      significantly and dose-dependently attenuated both development and expression of
      morphine dependence after chronic or acute administration. These data suggest
      that Rhodiola rosea L. may have human therapeutic potential for treatment of
      opioid addiction.

PMID- 20142300
TI  - Age-dependent effects of methylphenidate in the prefrontal cortex: evidence from
      electrophysiological and Arc gene expression measurements.
AB  - Methylphenidate, a drug widely used for attention deficit hyperactivity disorder
      in children, may affect neuronal function differently in young and adult
      subjects, particularly in the prefrontal cortex, a brain structure that does not
      fully develop until adulthood. We compared the impact of development on the
      effects of methylphenidate on single unit electrical activity and mRNA expression
      of the effector immediate early gene activity-regulated cytoskeletal-associated
      protein (Arc) following methylphenidate in the prefrontal cortex in adult (more
      than 60 days old) and juvenile (25-35 days old) rats. Methylphenidate,
      administered under urethane anaesthesia to adult rats, at doses ranging from 1
      mg/kg to 3 mg/kg intravenously, exerts a progressive activation of firing of
      prefrontal cortex neurones (30% to 84% from baseline). This activation was
      significantly lower in the juvenile rats, reaching only 37% of baseline levels at
      the highest dose (3 mg/kg, intravenous). In adults, methylphenidate (4 mg/kg
      intraperitoneal) produced marked increases in Arc mRNA levels compared with
      saline controls by 123% and 164% in cingulated and orbital cortex, respectively.
      Corresponding values for the juvenile rats were significantly lower (42% and
      79%). In summary, this multi-approach investigation showed that the reactivity of
      prefrontal cortex neurones to methylphenidate differs markedly in juvenile and
      adult rats.

PMID- 20142301
TI  - PG01037, a novel dopamine D3 receptor antagonist, inhibits the effects of
      methamphetamine in rats.
AB  - Our previous studies have shown that the selective dopamine D(3) receptor
      antagonists SB-277011A or NGB 2904 significantly attenuate cocaine self
      administration under a progressive-ratio reinforcement schedule and cocaine-,
      methamphetamine- or nicotine-enhanced brain stimulation reward. However, the poor
      bioavailability of SB-277011A has limited its potential use in humans. In the
      present study, we investigated the effects of the novel D(3) receptor antagonist
      PG01037 on methamphetamine self-administration, methamphetamine-associated cue
      induced reinstatement of drug seeking and methamphetamine-enhanced brain
      stimulation reward. Rats were allowed to intravenously self-administer
      methamphetamine under fixed-ratio 2 and progressive-ratio reinforcement
      conditions, and then the effects of PG01037 on methamphetamine self
      administration and cue-induced reinstatement were assessed. Additional groups of
      rats were trained for intracranial electrical brain stimulation reward and the
      effects of PG01037 and methamphetamine on brain stimulation reward were assessed.
      Acute intraperitoneal administration of PG01037 (3, 10, 30 mg/kg) failed to alter
      methamphetamine or sucrose self-administration under fixed-ratio 2 reinforcement,
      but significantly lowered the break-point levels for methamphetamine or sucrose
      self-administration under progressive-ratio reinforcement. In addition, PG01037
      significantly inhibited methamphetamine-associated cue-triggered reinstatement of
      drug-seeking behavior and methamphetamine-enhanced brain stimulation reward.
      These data suggest that the novel D(3) antagonist PG01037 significantly
      attenuates the rewarding effects as assessed by progressive-ratio self
      administration and brain stimulation reward, and inhibits methamphetamine
      associated cue-induced reinstatement of drug-seeking behavior These findings
      support the potential use of PG01037 or other selective D(3) antagonists in the
      treatment of methamphetamine addiction.

PMID- 20142302
TI  - Central nervous system effects of haloperidol on THC in healthy male volunteers.
AB  - In this study, the hypothesis that haloperidol would lead to an amelioration of
      Delta9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was
      investigated. In a double-blind, placebo-controlled, partial three-way crossover
      ascending dose study the effects of THC, haloperidol and their combination were
      investigated in 35 healthy, male mild cannabis users, measuring Positive and
      Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and
      psychedelic effects, saccadic and smooth pursuit eye measurements,
      electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task,
      hormone levels and pharmacokinetics. Compared with placebo, THC significantly
      decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test
      performance, immediate and delayed word recall and prolactin concentrations, and
      significantly increased positive and general Positive and Negative Syndrome Scale
      score, Visual Analogue Scales feeling high, Body Sway and electroencephalography
      alpha. Haloperidol reversed the THC-induced positive Positive and Negative
      Syndrome Scale increase to levels observed with haloperidol alone, but not THC
      induced 'high' feelings. Compared with placebo, haloperidol significantly
      decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and
      immediate and delayed word recall and significantly increased Body Sway,
      electroencephalography theta and prolactin levels. THC-induced increases in
      positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales
      feeling high were reversed by haloperidol. This indicates that psychotic-like
      effects induced by THC are mediated by dopaminergic systems, but that other
      systems are involved in 'feeling high'. Additionally, the clear reductions of
      psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that
      THC administration may be a useful pharmacological cannabinoid model for
      psychotic effects in healthy volunteers.

PMID- 20142303
TI  - CNS toxicity involving methylene blue: the exemplar for understanding and
      predicting drug interactions that precipitate serotonin toxicity.
AB  - Methylene blue has only recently been noted to cause severe central nervous
      system toxicity. Methylene blue is used for various conditions, including,
      intravenously, in methemoglobinemia, vasoplegia and as an aid to
      parathyroidectomy (at doses of 1-7.5 mg kg(-1)). This review of the current
      evidence concludes that 13 of 14 of the reported cases of CNS toxicity were
      serotonin toxicity that met the Hunter Serotonin Toxicity Criteria. That has
      important preventative and treatment implications. Serotonin toxicity is
      precipitated by the monoamine oxidase inhibitor (MAOI) property of methylene blue
      interacting with serotonin reuptake inhibitors. Serotonin toxicity is reviewed,
      using the lessons inherent in the methylene blue story and experience, to
      illustrate how the mechanisms and potency of serotonergic drugs interact to
      determine severity. Recent human data showed that an intravenous dose of only
      0.75 mg kg(-1) of methylene blue produced a peak plasma concentration of 500 ng
      ml(-1) (1.6 uM), indicating that the concentration in the central nervous system
      reaches a level that inhibits monoamine oxidase A. That is consonant with the
      actual occurrence of severe serotonin toxicity in humans at the dose of only 1 mg
      kg(-1). It seems that all proposed uses of methylene blue entail levels that
      block monoamine oxidase, so cessation of serotonin reuptake inhibitors should be
      very carefully considered before using methylene blue.

PMID- 20142304
TI  - The long-term effectiveness of clozapine and lamotrigine in a patient with
      treatment-resistant rapid-cycling bipolar disorder.
AB  - The challenges in the management of treatment-resistant rapid-cycling bipolar
      disorder are multifaceted and represent a significant burden to the patient.
      There is a need for more exploration into the potential utility of various
      combination therapies in the setting of severe affective states. A 52-year-old
      woman with a history of severe treatment-resistant rapid-cycling bipolar
      affective disorder (BPAD) was hospitalized for the treatment of a severe mixed
      episode. The introduction of lamotrigine and clozapine in combination proved
      remarkably effective and well tolerated in both the acute management and in
      subsequent maintenance. The patient has remained asymptomatic during the 5-year
      follow-up without any further mood disturbance. Lamotrigine and clozapine are
      among the less-prescribed agents for BPAD and there is as yet little research
      into their use in combination. It is possible that these agents have
      complementary modes of action on various facets of the affective pathology,
      resulting in superior mood stabilization in this patient.

PMID- 20142305
TI  - Further evidence supporting the influence of brain-derived neurotrophic factor on
      the outcome of bipolar depression: independent effect of brain-derived
      neurotrophic factor and harm avoidance.
AB  - Brain-derived neurotrophic factor is a candidate gene for response to
      antidepressant treatment. However, response to pharmacological treatments is
      moderated by both genetic and other factors within individuals. For example,
      there is evidence of an influence of the temperamental trait of harm avoidance on
      the outcome of depressive disorders. In the present study we aimed to investigate
      the effect of the brain-derived neurotrophic factor gene on medium-term outcome
      in a naturalistic sample of 86 depressed bipolar spectrum patients, taking into
      account harm avoidance. Both single marker and haplotypes were significantly
      associated with severity of depression at month 6 after treatment initiation. The
      haplotype comprising the A-C alleles was associated with a poorer outcome. Harm
      avoidance maintained a significant effect on depressive outcome in bipolar
      disorder, independently from brain-derived neurotrophic factor genotypes.
      However, harm avoidance s influence appeared to be more consistent in patients
      carrying the protective G-T combination of alleles. Our results indicate brain
      derived neurotrophic factor as involved in the outcome of depression in bipolar
      disorder. Harm avoidance did not interact with brain-derived neurotrophic factor
      genotypes, though its effect was still significant. Given that many factors may
      influence response to pharmacological treatments, studies that consider
      personality and other individual characteristics are warranted also in
      pharmacogenetic investigations.

PMID- 20142306
TI  - Desmopressin as a pharmacological tool in vasopressinergic hypothalamus-pituitary
      adrenal axis modulation: neuroendocrine, cardiovascular and coagulatory effects.
AB  - Arginine-vasopressin (AVP) is a physiological co-activator of the hypothalamus
      pituitary-adrenal (HPA) axis, together with corticotrophin releasing hormone
      (CRH). A synthetic analogue of AVP, desmopressin (dDAVP), is often used as a
      pharmacological tool to assess co-activation in health and disease. The relation
      between dDAVP's neuroendocrine, cardiovascular, pro-coagulatory, anti-diuretic
      and non-specific stress effects has not been studied. A randomized, double-blind,
      placebo-controlled, three-way crossover study was performed in 12 healthy male
      and female volunteers (6 : 6). dDAVP was administered intravenously as a 10 MUg
      bolus (over 1 min) or a 30 MUg incremental infusion (over 60 min).
      Neuroendocrine, cardiovascular, pro-coagulatory, anti-diuretic effects and
      adverse events (AEs) were recorded, and autonomic nervous system (ANS) activation
      evaluated. The incremental infusion reached 1.8-fold higher dDAVP concentrations
      than the bolus. Neuroendocrine effects were similar for the 10 MUg dDAVP bolus
      and the 30 MUg incremental infusion, while cardiovascular and coagulatory effects
      were greater with the 30 ug dose. Osmolality and ANS activity remained
      uninfluenced. AEs corresponded to dDAVP's side-effect profile. In conclusion, the
      neuroendocrine effects of a 10 MUg dDAVP bolus administered over 1 min are
      similar to those of a 30 MUg incremental infusion administered over one hour,
      despite higher dDAVP concentrations after the infusion. Cardiovascular and
      coagulatory effects showed clear dose-related responses. A 10 MUg dDAVP bolus is
      considered a safe vasopressinergic function test at which no confounding effects
      of systemic or autonomic stress were seen.

PMID- 20142307
TI  - Utility of saccadic eye movement analysis as an objective biomarker to detect the
      sedative interaction between opioids and sleep deprivation in opioid-naive and
      opioid-tolerant populations.
AB  - Analysis of saccadic eye movements (SEMs) has previously been used to detect drug
      and sleep-deprivation-induced sedation, but never in combination. We compared
      the effects of sleep deprivation and opioids on 10 opioid-naive with nine opioid
      tolerant participants. The naive-participant study evaluated the effects of sleep
      deprivation alone, morphine alone and the combination; the tolerant-participant
      study compared day-to-day effects of alternate-daily-dosed buprenorphine and the
      combination of buprenorphine on the dosing day with sleep deprivation.
      Psychomotor impairment was measured using SEMs, a 5-minute pupil adaptation test
      (PAT), pupil light reflex (PLR) and alertness visual analogue scale (AVAS). The
      PAT and PLR did not detect sleep deprivation, in contrast to previous studies.
      Whilst consistently detecting sleep deprivation, the AVAS also detected
      buprenorphine in the tolerant study, but not morphine in the naive study. SEMs
      detected morphine alone and sleep deprivation alone as well as an additive
      interaction in the naive study and the effect of sleep deprivation in the
      tolerant study. The alternate-day buprenorphine dosing did not alter SEMs. The
      current study revealed greater SEMs, but not AVAS impairment in tolerant versus
      naive participants. The current study demonstrates that objective measures
      provide additional information to subjective measures and thus should be used in
      combination.

PMID- 20142308
TI  - The effects of the glycine reuptake inhibitor R213129 on the central nervous
      system and on scopolamine-induced impairments in psychomotor and cognitive
      function in healthy subjects.
AB  - In this study the effects of R213129, a selective glycine transporter 1
      inhibitor, on central nervous system function were investigated in healthy males
      in the absence and presence of scopolamine. This was a double-blind, placebo
      controlled, 4-period crossover ascending dose study evaluating the following
      endpoints: body sway, saccadic and smooth pursuit eye movements, pupillometry,
      electroencephalography, visual analogue scales for alertness, mood, calmness and
      psychedelic effects, adaptive tracking, finger tapping, Visual and Verbal
      Learning Task, Stroop test, hormone levels and pharmacokinetics. R213129 dose
      levels were selected based on exposure levels that blocked the GlyT1 sites >50%
      in preclinical experiments. Forty-three of the 45 included subjects completed the
      study. Scopolamine significantly affected almost every central nervous system
      parameter measured in this study. R213129 alone compared with placebo did not
      elicit pharmacodynamic changes. R213129 had some small effects on scopolamine
      induced central nervous system impairments. Scopolamine-induced finger tapping
      impairment was further enhanced by 3 mg R213129 with 2.0 taps/10 seconds (95% CI 
      4.0, -0.1), electroencephalography alpha power was increased by 10 mg R213129
      with respectively 12.9% (0.7, 26.6%), scopolamine-induced impairment of the
      Stroop test was partly reversed by 10 mg R213129 with 59 milliseconds (-110, -7).
      Scopolamine produced robust and consistent effects in psychomotor and cognitive
      function in healthy volunteers. The most logical reason for the lack of R213129
      effects seems to be that the central nervous system concentrations were too low.
      The effects of higher doses in healthy volunteers and the clinical efficacy in
      patients remain to be established.

PMID- 20142309
TI  - MRI of the corpus callosum in multiple sclerosis: association with disability.
AB  - Inflammatory demyelination and axon damage in the corpus callosum are prominent
      features of multiple sclerosis (MS) and may partially account for impaired
      performance on complex tasks. The objective of this article was to characterize
      quantitative callosal MRI abnormalities and their association with disability. In
      69 participants with MS and 29 healthy volunteers, lesional and extralesional
      callosal MRI indices were estimated via diffusion tensor tractography. expanded
      disability status scale (EDSS) and MS functional composite (MSFC) scores were
      recorded in 53 of the participants with MS. All tested callosal MRI indices were
      diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51).
      Scores on the overall MSFC and its paced serial auditory addition test (PASAT)
      and 9-hole peg test components were correlated with callosal fractional
      anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity
      (r = -0.29, -0.30, and -0.31) but not with overall callosal volume or callosal
      lesion volume; the PASAT score was more weakly correlated with callosal
      magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were
      associated with impaired PASAT performance and posterior abnormalities with slow
      performance on the 9-hole peg test. In conclusion, abnormalities in the corpus
      callosum can be assessed with quantitative MRI and are associated with cognitive
      and complex upper-extremity dysfunction in MS.

PMID- 20142310
TI  - Optic neuritis incidence is increased in spring months in patients with
      asymptomatic demyelinating lesions.
AB  - Optic neuritis (ON) patients can be divided into two groups based on the presence
      or absence of asymptomatic demyelinating lesions (ADLs) on brain MRI. The
      presence of ADLs is associated with an increased risk of progression to
      clinically definite multiple sclerosis (CDMS). The clinical data and brain MRI of
      110 patients with acute unilateral ON were analyzed. Patients with ADLs had a
      significantly higher incidence of ON in spring months as compared with patients
      with no ADLs (p = 0.0024). Increased incidence of ON in spring months was seen in
      patients with ADLs whether or not they were diagnosed with CDMS on follow-up.

PMID- 20142312
TI  - Survivors of childhood cancer. Integrated follow-up is needed.

PMID- 20142313
TI  - Xenotransplantation. Not a solution.

PMID- 20142315
TI  - Comorbid disease in psoriasis. Don't forget mental illnesses.

PMID- 20142316
TI  - Britain on the rocks. Politicians, trust the public.

PMID- 20142317
TI  - Britain on the rocks. Potential pitfalls.

PMID- 20142319
TI  - The role of interventional radiology in trauma.

PMID- 20142323
TI  - Interaction of serotonin reuptake inhibitors with tamoxifen.

PMID- 20142324
TI  - Transforming growth factor-beta1 induces expression of human coagulation factor
      XII via Smad3 and JNK signaling pathways in human lung fibroblasts.
AB  - Coagulation factor XII (FXII) is a liver-derived serine protease involved in
      fibrinolysis, coagulation, and inflammation. The regulation of FXII expression is
      largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a
      multifunctional cytokine that has been linked to several pathological processes,
      including tissue fibrosis by modulating procoagulant and fibrinolytic activities.
      This study investigated whether TGF-beta1 may regulate FXII expression in human
      lung fibroblasts. Treatment of human lung fibroblasts with TGF-beta1 resulted in
      a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and
      Akt, and phosphorylation and translocation into the nucleus of Smad3. However,
      TGF-beta1-induced FXII expression was repressed only by the JNK inhibitor and JNK
      and Smad3 antisense oligonucleotides but not by MEK, p38, or phosphoinositide 3
      kinase blockers. JNK inhibition had no effect on TGF-beta1-induced Smad3
      phosphorylation, association with Smad4, and its translocation into the nucleus
      but strongly suppressed Smad3-DNA complex formation. FXII promoter analysis
      revealed that the -299/+1 region was sufficient for TGF-beta1 to induce FXII
      expression. Sequence analysis of this region detected a potential Smad-binding
      element at position -272/-269 (SBE-(-272/-269)). Chromatin immunoprecipitation
      and streptavidin pulldown assays demonstrated TGF-beta1-dependent Smad3 binding
      to SBE-(-272/-269). Mutation or deletion of SBE-(-272/-269) substantially reduced
      TGF-beta1-mediated activation of the FXII promoter. Clinical relevance was
      demonstrated by elevated FXII levels and its co-localization with fibroblasts in
      the lungs of patients with acute respiratory distress syndrome. Our results show
      that JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression
      in human lung fibroblasts and implicate its possible involvement in pathological
      conditions characterized by elevated TGF-beta1 levels.

PMID- 20142325
TI  - Selective serotonin reuptake inhibitors and breast cancer mortality in women
      receiving tamoxifen: a population based cohort study.
AB  - OBJECTIVE: To characterise whether some selective serotonin reuptake inhibitor
      (SSRI) antidepressants reduce tamoxifen's effectiveness by inhibiting its
      bioactivation by cytochrome P450 2D6 (CYP2D6). DESIGN: Population based cohort
      study. PARTICIPANTS: Women living in Ontario aged 66 years or older treated with
      tamoxifen for breast cancer between 1993 and 2005 who had overlapping treatment
      with a single SSRI. MAIN OUTCOME MEASURES: Risk of death from breast cancer after
      completion of tamoxifen treatment, as a function of the proportion of time on
      tamoxifen during which each SSRI had been co-prescribed. RESULTS: Of 2430 women
      treated with tamoxifen and a single SSRI, 374 (15.4%) died of breast cancer
      during follow-up (mean follow-up 2.38 years, SD 2.59). After adjustment for age,
      duration of tamoxifen treatment, and other potential confounders, absolute
      increases of 25%, 50%, and 75% in the proportion of time on tamoxifen with
      overlapping use of paroxetine (an irreversible inhibitor of CYP2D6) were
      associated with 24%, 54%, and 91% increases in the risk of death from breast
      cancer, respectively (P<0.05 for each comparison). By contrast, no such risk was
      seen with other antidepressants. We estimate that use of paroxetine for 41% of
      tamoxifen treatment (the median overlap in our sample) would result in one
      additional breast cancer death within five years of cessation of tamoxifen for
      every 19.7 (95% confidence interval 12.5 to 46.3) patients so treated; the risk
      with more extensive overlap would be greater. CONCLUSION: Paroxetine use during
      tamoxifen treatment is associated with an increased risk of death from breast
      cancer, supporting the hypothesis that paroxetine can reduce or abolish the
      benefit of tamoxifen in women with breast cancer.

PMID- 20142326
TI  - Convergent origins and rapid evolution of spliced leader trans-splicing in
      metazoa: insights from the ctenophora and hydrozoa.
AB  - Replacement of mRNA 5' UTR sequences by short sequences trans-spliced from
      specialized, noncoding, spliced leader (SL) RNAs is an enigmatic phenomenon,
      occurring in a set of distantly related animal groups including urochordates,
      nematodes, flatworms, and hydra, as well as in Euglenozoa and dinoflagellates.
      Whether SL trans-splicing has a common evolutionary origin and biological
      function among different organisms remains unclear. We have undertaken a
      systematic identification of SL exons in cDNA sequence data sets from non
      bilaterian metazoan species and their closest unicellular relatives. SL exons
      were identified in ctenophores and in hydrozoan cnidarians, but not in other
      cnidarians, placozoans, or sponges, or in animal unicellular relatives. Mapping
      of SL absence/presence obtained from this and previous studies onto current
      phylogenetic trees favors an evolutionary scenario involving multiple origins for
      SLs during eumetazoan evolution rather than loss from a common ancestor. In both
      ctenophore and hydrozoan species, multiple SL sequences were identified, showing
      high sequence diversity. Detailed analysis of a large data set generated for the
      hydrozoan Clytia hemisphaerica revealed trans-splicing of given mRNAs by multiple
      alternative SLs. No evidence was found for a common identity of trans-spliced
      mRNAs between different hydrozoans. One feature found specifically to
      characterize SL-spliced mRNAs in hydrozoans, however, was a marked adenosine
      enrichment immediately 3' of the SL acceptor splice site. Our findings of high
      sequence divergence and apparently indiscriminate use of SLs in hydrozoans, along
      with recent findings in other taxa, indicate that SL genes have evolved rapidly
      in parallel in diverse animal groups, with constraint on SL exon sequence
      evolution being apparently rare.

PMID- 20142328
TI  - Predominant cone photoreceptor dysfunction in a hyperglycaemic model of non
      proliferative diabetic retinopathy.
AB  - Approximately 2.5 million people worldwide are clinically blind because of
      diabetic retinopathy. In the non-proliferative stage, the pathophysiology of this
      ocular manifestation of diabetes presents as morphological and functional
      disruption of the retinal vasculature, and dysfunction of retinal neurons.
      However, it is uncertain whether the vascular and neuronal changes are
      interdependent or independent events. In addition, the identity of the retinal
      neurons that are most susceptible to the hyperglycaemia associated with diabetes
      is unclear. Here, we characterise a novel model of non-proliferative diabetic
      retinopathy in adult zebrafish, in which the zebrafish were subjected to
      oscillating hyperglycaemia for 30 days. Visual function is diminished in
      hyperglycaemic fish. Significantly, hyperglycaemia disrupts cone photoreceptor
      neurons the most, as evidenced by prominent morphological degeneration and
      dysfunctional cone-mediated electroretinograms. Disturbances in the morphological
      integrity of the blood-retinal barrier were also evident. However, we demonstrate
      that these early vascular changes are not sufficient to induce cone photoreceptor
      dysfunction, suggesting that the vascular and neuronal complications in diabetic
      retinopathy can arise independently. Current treatments for diabetic retinopathy
      target the vascular complications. Our data suggest that cone photoreceptor
      dysfunction is a clinical hallmark of diabetic retinopathy and that the
      debilitating blindness associated with diabetic retinopathy may be halted by
      neuroprotection of cones.

PMID- 20142327
TI  - Complementary interplay between matrix metalloproteinase-9, vascular endothelial
      growth factor and osteoclast function drives endochondral bone formation.
AB  - Long bone development depends on endochondral bone formation, a complex process
      requiring exquisite balance between hypertrophic cartilage (HC) formation and its
      ossification. Dysregulation of this process may result in skeletal dysplasias and
      heterotopic ossification. Endochondral ossification requires the precise
      orchestration of HC vascularization, extracellular matrix remodeling, and the
      recruitment of osteoclasts and osteoblasts. Matrix metalloproteinase-9 (MMP-9),
      vascular endothelial growth factor (VEGF) and osteoclasts have all been shown to
      regulate endochondral ossification, but how their function interrelates is not
      known. We have investigated the functional relationship among these regulators of
      endochondral ossification, demonstrating that they have complementary but non
      overlapping functions. MMP-9, VEGF and osteoclast deficiency all cause impaired
      growth plate ossification resulting in the accumulation of HC. VEGF mRNA and
      protein expression are increased at the MMP-9-/- growth plate, and VEGF activity
      contributes to endochondral ossification since sequestration of VEGF by soluble
      receptors results in further inhibition of growth plate vascularization and
      ossification. However, VEGF bioavailability is still limited in MMP-9 deficiency,
      as exogenous VEGF is able to rescue the MMP-9-/- phenotype, demonstrating that
      MMP-9 may partially, but not fully, regulate VEGF bioavailability. The
      organization of the HC extracellular matrix at the MMP-9-/- growth plate is
      altered, supporting a role for MMP-9 in HC remodeling. Inhibition of VEGF impairs
      osteoclast recruitment, whereas MMP-9 deficiency leads to an accumulation of
      osteoclasts at the chondro-osseous junction. Growth plate ossification in
      osteoclast-deficient mice is impaired in the presence of normal MMP-9 expression,
      indicating that other osteoclastic functions are also necessary. Our data
      delineate the complementary interplay between MMP-9, VEGF and osteoclast function
      that is necessary for normal endochondral bone formation and provide a molecular
      framework for investigating the molecular defects contributing to disorders of
      endochondral bone formation.

PMID- 20142329
TI  - Deficient forward transduction and enhanced reverse transduction in the alpha
      tectorin C1509G human hearing loss mutation.
AB  - Most forms of hearing loss are associated with loss of cochlear outer hair cells
      (OHCs). OHCs require the tectorial membrane (TM) for stereociliary bundle
      stimulation (forward transduction) and active feedback (reverse transduction).
      Alpha tectorin is a protein constituent of the TM and the C1509G mutation in
      alpha tectorin in humans results in autosomal dominant hearing loss. We
      engineered and validated this mutation in mice and found that the TM was
      shortened in heterozygous Tecta(C1509G/+) mice, reaching only the first row of
      OHCs. Thus, deficient forward transduction renders OHCs within the second and
      third rows non-functional, producing partial hearing loss. Surprisingly, both
      Tecta(C1509G/+) and Tecta(C1509G/C1509G) mice were found to have increased
      reverse transduction as assessed by sound- and electrically-evoked otoacoustic
      emissions. We show that an increase in prestin, a protein necessary for
      electromotility, in all three rows of OHCs underlies this phenomenon. This mouse
      model demonstrates a human hearing loss mutation in which OHC function is altered
      through a non-cell-autonomous variation in prestin.

PMID- 20142330
TI  - Lkb1 inactivation is sufficient to drive endometrial cancers that are aggressive
      yet highly responsive to mTOR inhibitor monotherapy.
AB  - Endometrial cancer--the most common malignancy of the female reproductive tract-
      arises from the specialized epithelial cells that line the inner surface of the
      uterus. Although significant advances have been made in our understanding of this
      disease in recent years, one significant limitation has been the lack of a
      diverse genetic toolkit for the generation of mouse models. We identified a novel
      endometrial-specific gene, Sprr2f, and developed a Sprr2f-Cre transgene for
      conditional gene targeting within endometrial epithelium. We then used this tool
      to generate a completely penetrant Lkb1 (also known as Stk11)-based mouse model
      of invasive endometrial cancer. Strikingly, female mice with homozygous
      endometrial Lkb1 inactivation did not harbor discrete endometrial neoplasms, but
      instead underwent diffuse malignant transformation of their entire endometrium
      with rapid extrauterine spread and death, suggesting that Lkb1 inactivation was
      sufficient to promote the development of invasive endometrial cancer. Mice with
      heterozygous endometrial Lkb1 inactivation only rarely developed tumors, which
      were focal and arose with much longer latency, arguing against the idea-
      suggested by some prior studies--that Lkb1 is a haploinsufficient tumor
      suppressor. Lastly, the finding that endometrial cancer cell lines were
      especially sensitive to the mTOR (mammalian target of rapamycin) inhibitor
      rapamycin prompted us to test its efficacy against Lkb1-driven endometrial
      cancers. Rapamycin monotherapy not only greatly slowed disease progression, but
      also led to striking regression of pre-existing tumors. These studies demonstrate
      that Lkb1 is a uniquely potent endometrial tumor suppressor, but also suggest
      that the clinical responses of some types of invasive cancers to mTOR inhibitors
      may be linked to Lkb1 status.

PMID- 20142331
TI  - Measuring cancer survival in populations: relative survival vs cancer-specific
      survival.
AB  - BACKGROUND: Two main methods of quantifying cancer patient survival are generally
      used: cancer-specific survival and relative survival. Both techniques are used to
      estimate survival in a single population, or to estimate differences in survival
      between populations. Arguments have been made that the relative survival approach
      is the only valid choice for population-based cancer survival studies because
      cancer-specific survival estimates may be invalid if there is misclassification
      of the cause of death. However, there has been little discussion, or evidence, as
      to how strong such biases may be, or of the potential biases that may result
      using relative survival techniques, particularly bias arising from the
      requirement for an external comparison group. METHODS: In this article we
      investigate the assumptions underlying both methods of survival analysis. We
      provide simulations relating to the impact of misclassification of death and non
      comparability of expected survival for cause-specific and relative survival
      approaches, respectively. RESULTS: For cause-specific analyses, bias through
      misclassification of cause of death resulted in error in descriptive analyses
      particularly of cancers with moderate or poor survival, but had smaller impact in
      analyses involving group comparisons. Relative survival ratio (RSR) estimations
      were robust in relation to non-comparability of comparison populations for single
      RSR but were less so in group comparisons where there was large variation in
      survival. CONCLUSIONS: Both cause-specific survival and relative survival are
      potentially valid epidemiological methods in population-based cancer survival
      studies, and the choice of method is dependent on the likely magnitude and
      direction of the biases in the specific analyses to be conducted.

PMID- 20142332
TI  - Standard and emerging therapies for metastatic differentiated thyroid cancer.
AB  - Differentiated thyroid cancer accounts for >90% of cases of thyroid cancer, with
      most patients having an excellent prognosis. Distant metastases occur in 10%-15%
      of patients, decreasing the overall 10-year survival rate in this group to 40%.
      Radioactive iodine has been the mainstay of treatment for distant metastases,
      with good results when lesions retain the ability to take up iodine. For patients
      with metastatic disease resistant to radioactive iodine, treatment options are
      few and survival is poor. Chemotherapy and external beam radiotherapy have been
      used in these patients, but with disappointing results. In recent years, our
      understanding of the molecular pathways involved in thyroid cancer has increased
      and a number of molecular targets have been identified. These targets include the
      proto-oncogenes BRAF and RET, known to be common mutations in thyroid cancer;
      vascular endothelial growth factor receptor and platelet-derived growth factor
      receptor, associated with angiogenesis; and the sodium-iodide symporter, with the
      aim of restoring its expression and hence radioactive iodine uptake. There are
      now multiple trials of tyrosine kinase inhibitors, angiogenesis inhibitors, and
      other novel agents available to patients with metastatic thyroid cancer. This
      review discusses both traditional and novel treatments for metastatic
      differentiated thyroid cancer with a particular focus on emerging treatments for
      patients with radioactive iodine-refractory disease.

PMID- 20142333
TI  - Sorafenib therapy for hepatocellular carcinoma in an HIV-HCV coinfected patient:
      a case report.
AB  - BACKGROUND/AIMS: HIV and hepatitis C virus (HCV) share common modes of
      transmission, resulting in about 33% incidence of coinfection among people
      infected with HIV. The survival benefit from highly effective antiretroviral
      therapy (HAART) for HIV infection is resulting in an increased incidence of
      hepatocellular carcinoma (HCC) in this population. There are no reports to date
      regarding the coadministration of HAART and sorafenib for hepatocellular
      carcinoma. METHODS: We report the case of a 42-year-old male patient coinfected
      with HIV and HCV who developed advanced HCC not amenable to curative therapy. The
      patient was treated with sorafenib, an oral multikinase inhibitor shown to lead
      to a longer median survival time and time to progression in patients with
      advanced HCC. Antiretroviral therapy was continued during sorafenib therapy.
      RESULTS: The patient achieved a partial tumor response after 3 months and
      continued to respond at subsequent assessments. His serum alpha-fetoprotein
      normalized from 2,172 IU/ml to 2 IU/ml. He had durable stable disease after 23
      months of therapy. Antiretroviral therapy was efficacious (CD4(+) lymphocyte
      count, 377/microl; HIV viremia, <50 copies/ml). The simultaneous administration
      of these therapies was well tolerated. No grade 3 or 4 toxicities were observed.
      Exacerbation of pre-existing hypertension, grade 2 diarrhea, and grade 1 skin
      reaction were observed. CONCLUSIONS: This is the first report in which sorafenib
      has been successfully used to treat HCC in a patient with HIV-HCV coinfection.

PMID- 20142335
TI  - Should multifaceted smoking cessation programmes be more widespread?

PMID- 20142334
TI  - The cognitive organization of music knowledge: a clinical analysis.
AB  - Despite much recent interest in the clinical neuroscience of music processing,
      the cognitive organization of music as a domain of non-verbal knowledge has been
      little studied. Here we addressed this issue systematically in two expert
      musicians with clinical diagnoses of semantic dementia and Alzheimer's disease,
      in comparison with a control group of healthy expert musicians. In a series of
      neuropsychological experiments, we investigated associative knowledge of musical
      compositions (musical objects), musical emotions, musical instruments (musical
      sources) and music notation (musical symbols). These aspects of music knowledge
      were assessed in relation to musical perceptual abilities and extra-musical
      neuropsychological functions. The patient with semantic dementia showed
      relatively preserved recognition of musical compositions and musical symbols
      despite severely impaired recognition of musical emotions and musical instruments
      from sound. In contrast, the patient with Alzheimer's disease showed impaired
      recognition of compositions, with somewhat better recognition of composer and
      musical era, and impaired comprehension of musical symbols, but normal
      recognition of musical emotions and musical instruments from sound. The findings
      suggest that music knowledge is fractionated, and superordinate musical knowledge
      is relatively more robust than knowledge of particular music. We propose that
      music constitutes a distinct domain of non-verbal knowledge but shares certain
      cognitive organizational features with other brain knowledge systems. Within the
      domain of music knowledge, dissociable cognitive mechanisms process knowledge
      derived from physical sources and the knowledge of abstract musical entities.

PMID- 20142336
TI  - A prospective, randomized, double-blind comparison of ultrasound-guided axillary
      brachial plexus blocks using 2 versus 4 injections.
AB  - INTRODUCTION: In this prospective, randomized, double-blind study, we compared
      the effectiveness and time efficiency of perioperative axillary blocks performed
      via 2 different techniques, 1 involving 2 and the other 4 separate skin
      punctures. METHODS: One hundred twenty patients undergoing upper limb surgery
      were randomized to receive either (1) an axillary brachial plexus block involving
      2 injections, with 30 mL local anesthetic injected posterior to the axillary
      artery (with redirection, as needed, to achieve circumferential spread), plus 10
      mL local anesthetic to the musculocutaneous nerve, guided by ultrasound (group 1,
      n = 56); or (2) 4 separate 10-mL injections to the median, ulnar, radial, and
      musculocutaneous nerves, using a combined ultrasound and neurostimulation
      technique (group 2, n = 58). All patients received 40 mL of 0.5% ropivacaine with
      1:400,000 epinephrine. The primary outcome was the success rate of the block,
      defined as anesthesia adequate for surgery. Secondary outcomes were the time to
      administer the block, time to the onset of motor-sensory block, time to surgical
      readiness, and incidence of adverse events. RESULTS: The 2-injection technique
      was slightly faster to administer (8 vs 11 minutes, P = 0.003). The mean nerve
      block score was slightly higher for the 4-injection group at the 10-, 15-, 20-,
      and 30-minute time points, but the cumulative percentages of blocks having taken
      effect were not significantly different over these time points, at 0.0%, 5.4%,
      12.5%, and 37.5% among those who had received a 2-injection block versus 6.9%,
      10.4%, 19.0%, and 48.3%, respectively, with the 4-injection block (P = 0.20).
      There was no difference in the percentage of patients with complete block by 30
      minutes (32.1% vs 37.5%, P = 0.55) or in final block success rates (89.3% vs
      87.9%, P = 0.99). CONCLUSIONS: An ultrasound-guided 2-injection axillary block
      may be as effective as, and more time efficient than, a 4-injection technique.

PMID- 20142337
TI  - Case report: telelaryngoscopy-guided flexible fiberoptic intubation for laryngeal
      rhinosporidiosis.
AB  - Rhinosporidiosis is a chronic granulomatous disease endemic in India and Sri
      Lanka. The causative microorganism, Rhinosporidium seeberi, remains a poorly
      understood pathogen, which has been described as an aquatic protistan parasite.
      Rhinosporidiosis presents as multiple polypoidal lesions affecting the mucosa of
      the nasal cavity, nasopharynx, and oropharynx. Intralaryngeal rhinosporidiosis is
      a rare entity and poses a challenge for management of the airway. In this case
      report, we highlight our technique in the management of the airway in a case of
      laryngeal rhinosporidiosis using a combination of fiberoptic bronchoscope and an
      endoscope. The technique was atraumatic and also avoided the potential for
      autoinoculation, which is a frequent cause of recurrence of this disease.

PMID- 20142338
TI  - A comparison of four techniques of emergency transcricoid oxygenation in a
      manikin.
AB  - Cricothyroidotomy is the final rescue maneuver in difficult airway management. We
      compared 4 techniques of oxygenation via the cricothyroid membrane in a manikin.
      The techniques were wire guided, trocar, cannula with jet ventilation, and blade
      technique (scalpel with endotracheal tube). In the wire-guided group, the time
      taken to ventilation was slower on all attempts, and there were no successful
      attempts in <40 seconds. There were no differences between the other groups at
      any time. Time to ventilation improved with repetition in all groups. Skills were
      retained at 1 month.

PMID- 20142339
TI  - Strepsils(r) tablets reduce sore throat and hoarseness after tracheal intubation.
AB  - BACKGROUND: Amyl-m-cresol (Strepsils(r)) has been successfully used in the
      prophylaxis and treatment of oral inflammations, but its effects on
      postintubation sore throat and hoarseness are unknown. We conducted this study to
      evaluate the effects of Strepsils in reducing postintubation sore throat and
      hoarseness. METHODS: One hundred fifty patients, ASA physical status I to II,
      scheduled to undergo general anesthesia and elective orthopedic or gynecologic
      surgery were enrolled. Participants were randomly allocated to receive either
      Strepsils or identical-looking placebo tablets immediately before arrival to the
      operating room. The incidence and severity of postoperative sore throat and
      hoarseness were evaluated immediately and 24 hours after surgery. RESULTS: The
      incidence of early postoperative sore throat was 13.7% and 33.3% and hoarseness
      was 12.3% and 26.4% in the Strepsils and placebo groups, respectively (P < 0.05).
      One day after surgery, the incidence of sore throat decreased to 6.8% and 18.1%
      in the Strepsils and control groups, respectively. The incidence of hoarseness 1
      day after the operation decreased to 8.2% in the Strepsils group and 19.4% in the
      placebo group, but the difference remained statistically significant (P < 0.05).
      CONCLUSION: Perioperative use of Strepsils tablets reduces postoperative sore
      throat and hoarseness of voice.

PMID- 20142340
TI  - Case report: continuous interscalene block associated with neck hematoma and
      postoperative sepsis.
AB  - Continuous peripheral nerve blockade is often used for the management of
      postoperative pain, even in ambulatory patients. The reported incidence of
      infectious complications after continuous nerve blockade is low. We report a case
      of Staphylococcus aureus sepsis after total shoulder arthroplasty in a patient
      who presented to her surgeon 8 days postoperatively with lethargy and labored
      breathing. Preoperatively, the patient had received a continuous interscalene
      block for analgesia that was associated with a neck hematoma. After readmission,
      exploratory laparotomy, and extensive hospital stay, the patient was discharged
      to an extended care facility in good condition.

PMID- 20142341
TI  - The influence of age on sample size calculation in acute pain trials using
      morphine consumption as an end point.
AB  - BACKGROUND: Many trials in acute postoperative pain use morphine consumption as
      an end point. Age has been shown to have a significant influence on morphine
      consumption but is rarely considered in end point analysis. METHODS: Simulation
      was used to investigate the effect of age on the power of various sample sizes to
      detect differences in morphine consumption in control and study groups. RESULTS:
      The sample sizes required for 80% power were approximately twice that predicted
      by a sample size program when comparing morphine consumption using a t test
      without adjustment for age. CONCLUSIONS: The model suggests that variations in
      age have a profound effect on sample size. Researchers may need to account for
      this to prevent both type 1 and type 2 error.

PMID- 20142342
TI  - Heparin dose response is independent of preoperative antithrombin activity in
      patients undergoing coronary artery bypass graft surgery using low heparin
      concentrations.
AB  - BACKGROUND: Unfractionated heparin's primary mechanism of action is to enhance
      the enzymatic activity of antithrombin (AT). We hypothesized that there would be
      a direct association between preoperative AT activity and both heparin dose
      response (HDR) and heparin sensitivity index (HSI) in patients undergoing
      coronary artery bypass graft surgery. METHODS: Demographic and perioperative data
      were collected from 304 patients undergoing primary coronary artery bypass graft
      surgery. AT activity was measured after induction of general anesthesia using a
      colorimetric method (Siemens Healthcare Diagnostics, Tarrytown, NY). Activated
      coagulation time (ACT), HDR, and HSI were measured using the Hepcon HMS Plus
      system (Medtronic, Minneapolis, MN). Heparin dose was calculated for a target ACT
      using measured HDR by the same system. Multivariate linear regression was
      performed to identify independent predictors of HDR. Subgroup analysis of
      patients with low AT activity (<80% normal; <0.813 U/mL) who may be at risk for
      heparin resistance was also performed. RESULTS: Mean baseline ACT was 135 +/- 18
      seconds. Mean calculated HDR was 98 +/- 21 s/U/mL. Mean baseline AT activity was
      0.93 +/- 0.13 U/mL. Baseline AT activity was not significantly associated with
      baseline or postheparin ACT, HDR, or HSI. Addition of AT activity to
      multivariable linear regression models of both HDR and HSI did not significantly
      improve model performance. Subgroup analysis of 49 patients with baseline AT <80%
      of normal levels did not reveal a relationship between low AT activity and HDR or
      HSI. Preoperative AT activity, HDR, and HSI were not associated with cardiac
      troponin I levels on the first postoperative day, intensive care unit duration,
      or hospital length of stay. CONCLUSION: Although enhancing AT activity is the
      primary mechanism by which heparin facilitates cardiopulmonary bypass
      anticoagulation, low preoperative AT activity is not associated with impaired
      response to heparin or to clinical outcomes when using target ACTs of 300 to 350
      seconds.

PMID- 20142343
TI  - An anesthetic management protocol to decrease respiratory complications after
      adenotonsillectomy in children with severe sleep apnea.
AB  - BACKGROUND: A high incidence of respiratory morbidity after adenotonsillectomy is
      reported in children with obstructive sleep apnea syndrome (OSAS). In an effort
      to decrease this morbidity, we implemented perioperative guidelines recommending
      an adjustment in the administration of opioids, dexamethasone, and atropine in
      children with OSAS who demonstrated recurrent episodes of profound hypoxemia
      during the perioperative sleep study. METHODS: We performed a retrospective
      review and compared results with historic data from 2001. The primary outcome
      variable was a major respiratory medical intervention (MMI(Respiratory)). The
      severity of OSAS was classified with the McGill Oximetry Scoring (MOS) system,
      and our focus was on those children demonstrating repetitive desaturation <80%
      (MOS4). RESULTS: The medical records of 292 children who underwent
      adenotonsillectomy between October 2002 and February 2006 met the inclusion
      criteria and 97 had been assigned MOS4. Eleven children (11.3%) required an
      MMI(Respiratory). In 2001, 8 children (29.6%), assigned MOS4, required an
      MMI(Respiratory). Comparing the new and old guidelines, the adjusted odds ratio
      for MMI(Respiratory) in MOS4 was 0.30 (95% CI: 0.10-0.85). The key elements
      achieving this reduction in MMI(Respiratory) were dexamethasone administration
      and a reduced opioid dosage. In 2002 to 2006, the intraoperative opioid dose,
      expressed in morphine equivalents, administered to the MOS4 group was 0.10 mg .
      kg(-1) (0.06-0.12 mg . kg(-1)), and the postoperative morphine dose was 0.02 mg .
      kg(-1) (0-0.07 mg . kg(-1)). Both doses were lower than the ones administered to
      the concurrent comparison group, P values <0.001. CONCLUSIONS: A change in
      practice that included a dexamethasone administration and a reduction in opioid
      administration to children with profound recurrent hypoxia reduced the incidence
      of MMI(Respiratory) by >50%.

PMID- 20142344
TI  - Synergistic interactions between paracetamol and oxcarbazepine in somatic and
      visceral pain models in rodents.
AB  - BACKGROUND: Combination therapy is a valid approach in pain treatment, in which a
      reduction of doses could reduce side effects and still achieve optimal analgesia.
      We examined the effects of coadministered paracetamol, a widely used non-opioid
      analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic
      properties, in a rat model of paw inflammatory hyperalgesia and in a mice model
      of visceral pain and determined the type of interaction between components.
      METHODS: The effects of paracetamol, oxcarbazepine, and their combinations were
      examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in
      rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In
      both models, drugs were coadministered in fixed-dose fractions of the 50%
      effective dose (ED(50)), and type of interaction was determined by isobolographic
      analysis. RESULTS: Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160
      mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug
      ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan
      injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral),
      oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and
      1/2 of a single drug ED(50)) significantly and dose dependently reduced the
      number of writhes. In both models, isobolographic analysis revealed a significant
      synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold
      reduction of doses of both drugs in combination, compared with single drugs
      ED(50). CONCLUSIONS: The synergistic interaction between paracetamol and
      oxcarbazepine provides new information about combination pain treatment and
      should be explored further in patients, especially with somatic and/or visceral
      pain.

PMID- 20142345
TI  - The relationship among thromboelastography, hemostatic variables, and bleeding
      after cardiopulmonary bypass surgery in children.
AB  - BACKGROUND: Mediastinal bleeding is common after pediatric cardiopulmonary bypass
      (CPB) surgery. Thromboelastography (TEG) may predict bleeding and provide insight
      into likely mechanisms. We aimed to (a) compare perioperative temporal profiles
      of TEG and laboratory hemostatic variables between patients with significant
      hemorrhage (BLEED) and those without (CONTROL), (b) investigate the relationship
      between TEG variables and routine hemostatic variables, and (c) develop a model
      for prediction of bleeding. METHODS: TEG and laboratory hemostatic variables were
      measured prospectively at 8 predefined times for 50 children weighing <20 kg
      undergoing CPB. RESULTS: Patients who bled demonstrated different TEG profiles
      than those who did not. This was most apparent after protamine administration and
      was partly attributable to inadequate heparin reversal, but was also associated
      with a significantly lower nadir in mean (sd) fibrinogen for the BLEED group
      compared with CONTROL group: 0.44 (0.18) and 0.71 (0.40) g/L, respectively (P =
      0.01). Significant nonlinear relationships were found between the majority of TEG
      and laboratory hemostatic variables. The strongest relationship was between the
      maximal amplitude and the platelet-fibrinogen product (logarithmic r(2) = 0.71).
      Clot strength decreased rapidly when (a) fibrinogen concentration was <1 g/L, (b)
      platelets were <120 x 10(9)/L, and (c) platelet-fibrinogen product was <100. A 2
      variable model including the activated partial thromboplastin time at induction
      of anesthesia and TEG mean amplitude postprotamine discriminated well for
      subsequent bleeding (C statistic 0.859). CONCLUSIONS: Hypofibrinogenemia and
      inadequate heparin reversal are 2 important factors contributing to clot strength
      and perioperative hemorrhage after pediatric CPB. TEG may be a useful tool for
      predicting and guiding early treatment of mediastinal bleeding in this group.

PMID- 20142346
TI  - Brief report: improved pain relief using intermittent bupivacaine injections at
      the donor site after breast reconstruction with deep inferior epigastric
      perforator flap.
AB  - BACKGROUND: Deep inferior epigastric perforator flap surgery usually results in
      postoperative pain from the donor site requiring opioids. METHOD: We examined the
      effect of bupivacaine 2.5 mg/mL, 20 mL given every third hour for 72 hours
      postoperatively through 2 thin catheters placed on the donor site in a double
      blind placebo-controlled study consisting of 2 x 20 patients. RESULTS: The
      bupivacaine group had significantly reduced pain at rest and during coughing. The
      placebo group needed 2 to 3 times more opioids in the 72-hour observation period.
      No difference was seen in the frequency of nausea or the consumption of
      antiemetic drugs. CONCLUSION: We conclude that intermittent delivery of
      bupivacaine at the abdominal donor site significantly reduces the postoperative
      pain and need for narcotic rescue medication.

PMID- 20142347
TI  - Review article: anesthetic management of patients undergoing deep brain
      stimulator insertion.
AB  - Deep brain stimulation is used for the treatment of patients with neurologic
      disorders who have an alteration of function, such as movement disorders and
      other chronic illnesses. The insertion of the deep brain stimulator (DBS) is a
      minimally invasive procedure that includes the placement of electrodes into deep
      brain structures for microelectrode recordings and intraoperative clinical
      testing and connection of the DBS to an implanted pacemaker. The anesthetic
      technique varies depending on the traditions and requirements of each institution
      performing these procedures and has included monitored anesthesia with local
      anesthesia, conscious sedation, and general anesthesia. The challenges and
      demands for the anesthesiologist in the care of these patients relate to the
      specific concerns of the patients with functional neurologic disorders, the
      effects of anesthetic drugs on microelectrode recordings, and the requirements of
      the surgical procedure, which often include an awake and cooperative patient. The
      purpose of this review is to familiarize anesthesiologists with deep brain
      stimulation by discussing the mechanism, the effects of anesthetic drugs, and the
      surgical procedure of DBS insertion, and the perioperative assessment,
      preparation, intraoperative anesthetic management, and complications in patients
      with functional neurologic disorders.

PMID- 20142348
TI  - Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a
      qualitative systematic review of analgesic efficacy for acute postoperative pain.
AB  - BACKGROUND: There has been a trend over recent years for combining a nonsteroidal
      antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain
      management. However, therapeutic superiority of the combination of paracetamol
      and an NSAID over either drug alone remains controversial. We evaluated the
      efficacy of the combination of paracetamol and an NSAID versus either drug alone
      in various acute pain models. METHODS: A systematic literature search of Medline,
      Embase, Cumulative Index to Nursing and Allied Health Literature, and PubMed
      covering the period from January 1988 to June 2009 was performed to identify
      randomized controlled trials in humans that specifically compared combinations of
      paracetamol with various NSAIDs versus at least 1 of these constituent drugs.
      Identified studies were stratified into 2 groups: paracetamol/NSAID combinations
      versus paracetamol or NSAIDs. We analyzed pain intensity scores and supplemental
      analgesic requirements as primary outcome measures. In addition, each study was
      graded for quality using a validated scale. RESULTS: Twenty-one human studies
      enrolling 1909 patients were analyzed. The NSAIDs used were ibuprofen (n = 6),
      diclofenac (n = 8), ketoprofen (n = 3), ketorolac (n = 1), aspirin (n = 1),
      tenoxicam (n = 1), and rofecoxib (n = 1). The combination of paracetamol and
      NSAID was more effective than paracetamol or NSAID alone in 85% and 64% of
      relevant studies, respectively. The pain intensity and analgesic supplementation
      was 35.0% +/- 10.9% and 38.8% +/- 13.1% lesser, respectively, in the positive
      studies for the combination versus paracetamol group, and 37.7% +/- 26.6% and
      31.3% +/- 13.4% lesser, respectively, in the positive studies for the combination
      versus the NSAID group. No statistical difference in median quality scores was
      found between experimental groups. CONCLUSION: Current evidence suggests that a
      combination of paracetamol and an NSAID may offer superior analgesia compared
      with either drug alone.

PMID- 20142349
TI  - Irreversible electroporation: a new challenge in "out of operating theater"
      anesthesia.
AB  - BACKGROUND: Bioelectrics, an interesting new area of medicine, combines pulsed
      high-voltage engineering with cell biology and has many potential applications.
      Pulsed electric current can be used to produce irreversible electroporation (IRE)
      of cell membranes with resulting cell death. This process has been shown to
      ablate tumors in animal studies. METHODS: A clinical trial of IRE as a tumor
      ablation therapy was performed at our institution. A pulsating direct current of
      20 to 50 A and 500 to 3000 V was delivered into metastatic or primary tumors in
      the liver, kidney, or lung via needle electrodes inserted under computed
      tomography (CT) or ultrasound guidance. Patients required a relaxant general
      anesthetic. We describe some challenges presented to anesthesiologists.
      Guidelines for anesthesia were produced and modified as issues became apparent.
      The patients' charts were audited throughout. RESULTS: We noted a number of
      issues. The electrical discharge produced generalized upper body muscular
      contractions requiring neuromuscular blockade. Two patients developed positional
      neuropraxia because of the extended arm position requested for CT scanning. After
      experimentation, we have developed a modified arm position. Some patients
      developed self-limiting ventricular tachycardias that are now minimized by using
      an electrocardiogram synchronizer. Three patients developed pneumothoraces as a
      result of the needle electrode insertion. CONCLUSIONS: Relaxant general
      anesthesia is required for IRE of the liver, lung, and kidney. An
      electrocardiogram synchronizer should be used to minimize the risk of
      arrhythmias. Attention to the position of the arms is required to maximize CT
      scan quality but minimize brachial plexus strain. Simple postoperative analgesia
      is all that is required in most patients.

PMID- 20142350
TI  - Technical communication: new teaching model for practicing ultrasound-guided
      regional anesthesia techniques: no perishable food products!
AB  - BACKGROUND: There is a pronounced learning curve for the technique of ultrasound
      guided regional anesthesia. Practicing with a simulator model has been shown to
      speed the acquisition of these skills for various ultrasound-guided procedures.
      However, commercial models for ultrasound-guided regional anesthesia may be too
      costly or not readily available. Models using turkey breasts or tofu blocks have
      the disadvantage of containing perishable food products that can be a source for
      infection. We describe an alternative inexpensive model that is made from
      nonperishable components readily available in the operating room. METHODS: The
      materials required include 1 clean used 500-mL bag of IV fluids, a bottle of
      Premisorb (TYCO Healthcare Group, Mansfield, MA), and a piece of foam material
      approximately 0.3 cm in diameter and 5 cm in length trimmed from operating room
      foam pads. After filling the IV bag with tap water and inserting the foam into
      the IV bag from the outlet port of the IV bag, one-third of a bottle of Premisorb
      (approximately 15 g) is poured into the IV bag. The outlet port of the bag is
      then sealed by taping the rubber stopper that originally came with the bag.
      RESULTS: Premisorb, a solidifying agent frequently used to absorb irrigating
      fluids or blood in operating room suction canisters, produces a gel-like material
      in the IV bag. The foam inserted into the bag creates a relatively hyperechoic
      target. This gel-like substance in the bag will seal the holes created after
      multiple practice needle insertions, resulting in minimal leakage. The
      semitransparent nature of the gel allows the trainee to visualize the target
      directly and on the ultrasound screen. CONCLUSION: The model we describe is
      inexpensive and easy to make from materials readily available in the operating
      room with the advantages of being nonperishable, easy to carry, and reusable.

PMID- 20142351
TI  - Echo rounds: discrete subvalvular aortic stenosis.

PMID- 20142352
TI  - Case report: successful treatment of a patient with trigeminal neuropathy using
      ziconotide.
AB  - A 50-year-old female patient with chronic neuropathic pain in the distribution of
      the second branch of the trigeminal nerve was unsuccessfully treated over several
      years. Intrathecal therapy with ziconotide was administered at an initial dose of
      0.33 microg/d, which was gradually increased by 0.7 microg/d. Subjective pain on
      the numeric rating scale was reduced from 9/10 to 3-4/10 at a dose of 6.3
      microg/d. Long-term treatment was continued at a ziconotide concentration of 12.5
      microg/mL and a daily dose of 3.9 microg/d by a SynchroMed Infusion System
      (Medtronic, Minneapolis, MN). Pain reduction was maintained in the follow-up
      observation period over 5 months.

PMID- 20142353
TI  - Functional properties of RYR1 mutations identified in Swedish patients with
      malignant hyperthermia and central core disease.
AB  - BACKGROUND: A diagnosis of malignant hyperthermia susceptibility by in vitro
      contraction testing can often only be performed at specialized laboratories far
      away from where patients live. Therefore, we have designed a protocol for genetic
      screening of the RYR1-cDNA and for functional testing of newly identified
      ryanodine receptor 1 (RYR1) gene variants in B lymphocytes isolated from
      peripheral blood samples drawn at local primary care centers. METHODS: B
      lymphocytes were isolated for the extraction of RYR1-mRNA and genomic DNA and for
      establishment of lymphoblastoid B cell lines in 5 patients carrying yet
      unclassified mutations in the RYR1. The B lymphoblastoid cell lines were used to
      study resting cytoplasmic calcium concentration, the peak calcium transient
      induced by the sarco(endo)plasmic reticulum Ca-ATPase inhibitor thapsigargin, and
      the dose-dependent calcium release induced by the ryanodine receptor agonist 4
      chloro-m-cresol. RESULTS: It was possible to extract mRNA for cDNA synthesis and
      to create B lymphocyte clones from all samples. All B lymphoblastoid cell lines
      carrying RYR1 candidate mutations showed significantly increased resting
      cytoplasmic calcium levels as well as a shift to lower concentrations of 4-chloro
      m-cresol inducing calcium release compared with controls. CONCLUSIONS: Peripheral
      blood samples are stable regarding RNA and DNA extraction and establishment of
      lymphoblastoid B cell lines after transportation at ambient temperature over
      large distances by ordinary mail. Functional tests on B cells harboring the newly
      identified amino acid substitutions indicate that they alter intracellular Ca2+
      homeostasis and are most likely causative of malignant hyperthermia.

PMID- 20142354
TI  - Review article: glucose measurement in the operating room: more complicated than
      it seems.
AB  - Abnormalities of blood glucose are common in patients undergoing surgery, and in
      recent years there has been considerable interest in tight control of glucose in
      the perioperative period. Implementation of any regime of close glycemic control
      requires more frequent measurement of blood glucose, a function for which small,
      inexpensive, and rapidly responding point-of-care devices might seem highly
      suitable. However, what is not well understood by many anesthesiologists and
      other staff caring for patients in the perioperative period is the lack of
      accuracy of home glucose meters that were designed for self-monitoring of blood
      glucose by patients. These devices have been remarketed to hospitals without
      appropriate additional testing and without an appropriate regulatory framework.
      Clinicians who are accustomed to the high level of accuracy of glucose
      measurement by a central laboratory device or by an automated blood gas analyzer
      may be unaware of the potential for harmful clinical errors that are caused by
      the inaccuracy exhibited by many self-monitoring of blood glucose devices,
      especially in the hypoglycemic range. Knowledge of the limitations of these
      meters is essential for the perioperative physician to minimize the possibility
      of a harmful measurement error. In this article, we will highlight these areas of
      interest and review the indications, technology, accuracy, and regulation of
      glucose measurement devices used in the perioperative setting.

PMID- 20142355
TI  - Use of state discharge abstract data to identify hospitals performing similar
      types of operative procedures.
AB  - INTRODUCTION: A hospital or anesthesia or surgical group that is making decisions
      to expand its practice benefits from knowledge of the types of surgical
      procedures performed at other hospitals. METHODS: Discharge abstract data were
      used to study 1 hospital in each of 3 states. A similarity index provided
      information on which other hospitals in each state were competitors and/or peer
      institutions. To reveal potential growth opportunities, Clinical Classifications
      Software (CCS) grouping of specific types of procedures into broad categories was
      combined with the similarity index. The internal Herfindahl index was used to
      quantify the heterogeneity of procedures within each CCS category. RESULTS:
      Although the similarity index between many pairs of hospitals was highly
      influenced by the common orthopedic procedures performed at most hospitals, the
      similarity index was dominated by a large number of different types of
      procedures. For some pairs of hospitals, there was considerable overlap between
      the different types of procedures performed at each institution. For other pairs
      of hospitals, the overlap was small. Consequently, large hospitals were not
      always similar to each other because of the wide range of procedures performed.
      Smaller community hospitals were not always similar to each other either. Some
      small hospitals were sometimes similar to large metropolitan hospitals.
      CONCLUSIONS: The similarity index is a robust and valid method for quantitatively
      comparing the numbers and types of inpatient surgical procedures performed at
      different hospitals. The similarity index, when combined with CCS categories, is
      useful for identifying opportunities that enable surgeons and anesthesiologists
      to better meet the needs of their communities.

PMID- 20142356
TI  - What will anesthesiologists be anesthetizing? Trends in neurosurgical procedure
      usage.
AB  - BACKGROUND: To anticipate future changes to the practice of neuroanesthesia, we
      examined the nationwide trends in frequently performed operative neurosurgery.
      METHODS: We used the Nationwide Inpatient Sample, a random sampling of
      approximately 20% of United States hospitals from 1993 to 2007. Eight categories
      of operative neurosurgery were developed, based on procedure codes from the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM). We tabulated total volume, mean length of stay, and inhospital
      mortality and calculated growth rates over the entire period, the most recent 5
      year period, and the most recent 2-year period. We examined annual volumes from
      1993 to 2007 for each neurosurgical category for the most common ICD-9-CM
      procedure code within each category. RESULTS: Intracranial endovascular
      procedures had the highest compound annual growth rate over the entire study
      period (32%), the most recent 4 years (29%), and the most recent 2 years (12%).
      Craniotomy for vascular surgery decreased over the entire period (-4.2%). Spinal
      fusion had the largest absolute increase over the study period (from 54,000 in
      1993 to 350,000 in 2007). All categories except craniotomy for vascular surgery
      had decreased length of stay across the study period, with compound annual growth
      rates of -1.2% (ventricular and thecal shunt) to -6.6% (deep brain stimulation).
      Intracranial endovascular procedures had a much higher growth rate of length of
      stay than vascular surgery over the most recent 2-year (14% vs 1.0%) and 5-year
      periods (5.6% vs 1.5%). CONCLUSIONS: The highest volume trends in operative
      neurosurgery are for spinal fusion (increasing at a rate of approximately 12,000
      procedures/y), craniotomy for tumors and other purposes (increasing at a rate of
      approximately 2,700 procedures/y), and a decrease in shunts (decreasing at a rate
      of approximately 3,000 per year). The data suggest that intracranial endovascular
      treatment remains relatively rare, but it is growing exponentially, and lengths
      of stay are increasing, whereas inhospital deaths are decreasing. The conclusions
      of this study are limited by the imprecise nature of the ICD-9-CM procedure
      codes, the categorization scheme we used, and by the sampling methods of the
      National Inpatient Sample.

PMID- 20142357
TI  - Control chart monitoring of the numbers of cases waiting when anesthesiologists
      do not bring in members of call team.
AB  - INTRODUCTION: An anesthesia group staffing agreement with a hospital often
      specifies the minimum number of operating rooms (ORs) to be covered during
      evening or weekend hours. Frequently, 1 anesthesiologist works in-house and
      others take call from home, coming in if multiple cases are waiting to be done.
      The anesthesiologist in-house sometimes does not bring in colleagues from home
      when the number of ORs he can supervise is less than the number specified in the
      agreement with the hospital (i.e., assignment is less than staffing). Queuing
      occurs even if managers have selected an appropriate number of ORs to be run
      during evenings and weekends (i.e., the number of cases [jobs] exceeds the number
      of ORs [identical machines] that are actually run). METHODS: In our study, we
      used a dataset without trend over 3 years to determine whether we could identify
      differences among anesthesiologists in queuing behavior. Negative binomial
      regression was used to model the number of cases waiting while the number of ORs
      running was fewer than allocated. Multiple variable regressions modeled waiting
      times among cases. The easy to construct Shewhart chart and the more complicated
      cumulative sum chart were then compared to test for outliers in the number of
      cases waiting. RESULTS: Queuing behavior was found to be homogeneous among the 33
      anesthesiologists (P > 0.28 among different statistical models). Weekend days
      differed from evenings. Shewhart and cumulative sum charts were comparable for
      detecting unusual variations. CONCLUSIONS: Anesthesiologists sometimes do not
      notify call team members when cases are waiting and the number of ORs running is
      less than allocated. The number of cases waiting, rather than the amount of
      waiting, is more appropriate for monitoring trends over time. Simple Shewhart
      charts can be used for monitoring contractually specified staffing.

PMID- 20142358
TI  - c-Myb promotes the survival of CD4+CD8+ double-positive thymocytes through
      upregulation of Bcl-xL.
AB  - Mechanisms that regulate the lifespan of CD4(+)CD8(+) double-positive (DP)
      thymocytes help shape the peripheral T cell repertoire. However, the molecular
      mechanisms controlling DP thymocyte survival remain poorly understood. The Myb
      proto-oncogene encodes a transcription factor required during multiple stages of
      T cell development. We demonstrate that Myb mRNA expression is upregulated as
      thymocytes differentiate from the double-negative into the metabolically
      quiescent, small, preselection DP stage during T cell development. Using a
      conditional deletion mouse model, we demonstrate that Myb-deficient DP thymocytes
      undergo premature apoptosis, resulting in a limited Tcralpha repertoire biased
      toward 5' Jalpha segment usage. Premature apoptosis occurs specifically in the
      small preselection DP compartment in an alphabetaTCR-independent manner and is a
      consequence of decreased Bcl-xL expression. Forced Bcl-xL expression is able to
      rescue survival, and reintroduction of c-Myb restores both Bcl-xL expression and
      the small preselection DP compartment. We further demonstrate that c-Myb promotes
      transcription at the Bcl2l1 locus via a genetic pathway that is independent of
      the expression of T cell-specific factor-1 or RORgammat, two transcription
      factors that induce Bcl-xL expression in T cell development. Thus, Bcl-xL is a
      novel mediator of c-Myb activity during normal T cell development.

PMID- 20142359
TI  - Protein kinase D1 is essential for the proinflammatory response induced by
      hypersensitivity pneumonitis-causing thermophilic actinomycetes Saccharopolyspora
      rectivirgula.
AB  - Hypersensitivity pneumonitis is an interstitial lung disease that results from
      repeated pulmonary exposure to various organic Ags, including Saccharopolyspora
      rectivirgula, the causative agent of farmer's lung disease. Although the
      contributions of proinflammatory mediators to the disease pathogenesis are
      relatively well documented, the mechanism(s) involved in the initiation of
      proinflammatory responses against the causative microorganisms and the
      contribution of signaling molecules involved in the host immune defense have not
      been fully elucidated. In the current study, we found that S. rectivirgula
      induces the activation of protein kinase D (PKD)1 in lung cells in vitro and in
      vivo. Activation of PKD1 by S. rectivirgula was dependent on MyD88. Inhibition of
      PKD by pharmacological PKD inhibitor Go6976 and silencing of PKD1 expression by
      small interfering RNA revealed that PKD1 is indispensable for S. rectivirgula
      mediated activation of MAPKs and NF-kappaB and the expression of various
      proinflammatory cytokines and chemokines. In addition, compared with controls,
      mice pretreated with Go6976 showed significantly suppressed alveolitis and
      neutrophil influx in bronchial alveolar lavage fluid and interstitial lung
      tissue, as well as substantially decreased myeloperoxidase activity in the lung
      after pulmonary exposure to S. rectivirgula. These results demonstrate that PKD1
      is essential for S. rectivirgula-mediated proinflammatory immune responses and
      neutrophil influx in the lung. Our findings also imply the possibility that PKD1
      is one of the critical factors that play a regulatory role in the development of
      hypersensitivity pneumonitis caused by microbial Ags and that inhibition of PKD1
      activation could be an effective way to control microbial Ag-induced
      hypersensitivity pneumonitis.

PMID- 20142360
TI  - Requirement for Runx proteins in IgA class switching acting downstream of TGF
      beta 1 and retinoic acid signaling.
AB  - IgA is a specific isotype required for mucosal immunity and is the most abundant
      Ab produced in vivo. Recently, several inductive signals for IgA class switch
      recombination have been identified; however, the molecular details of the action
      of these signals and the specific factors acting in B cells remain elusive. In
      this study, we show that combination of retinoic acid (RA) and TGF-beta1 with
      other factors induced a much higher frequency of IgA-switched cells than reported
      previously. In addition, IgA production is severely impaired in Runx2-Runx3
      double-deficient mice. In Runx2-Runx3-deficient B cells, both RA- and TGF-beta1
      dependent inductions of alpha germline transcription are completely blocked.
      These data suggest that Runx proteins play an essential role in IgA class
      switching acting downstream of RA and TGF-beta1 signaling.

PMID- 20142361
TI  - Mechanism of T cell tolerance induced by myeloid-derived suppressor cells.
AB  - Ag-specific T cell tolerance plays a critical role in tumor escape. Recent
      studies implicated myeloid-derived suppressor cells (MDSCs) in the induction of
      CD8(+) T cell tolerance in tumor-bearing hosts. However, the mechanism of this
      phenomenon remained unclear. We have found that incubation of Ag-specific CD8(+)
      T cells, with peptide-loaded MDSCs, did not induce signaling downstream of TCR.
      However, it prevented subsequent signaling from peptide-loaded dendritic cells.
      Using double TCR transgenic CD8(+) T cells, we have demonstrated that MDSC
      induced tolerance to only the peptide, which was presented by MDSCs. T cell
      response to the peptide specific to the other TCR was not affected. Incubation of
      MDSCs with Ag-specific CD8(+) T cells caused nitration of the molecules on the
      surface of CD8(+) T cells, localized to the site of physical interaction between
      MDSC and T cells, which involves preferentially only TCR specific for the peptide
      presented by MDSCs. Postincubation with MDSCs, only nitrotyrosine-positive CD8(+)
      T cells demonstrated profound nonresponsiveness to the specific peptide, whereas
      nitrotyrosine-negative CD8(+) T cells responded normally to that stimulation.
      MDSCs caused dissociation between TCR and CD3zeta molecules, disrupting TCR
      complexes on T cells. Thus, these data describe a novel mechanism of Ag-specific
      CD8(+) T cell tolerance in cancer.

PMID- 20142362
TI  - ADP-ribosylation controls the outcome of tolerance or enhanced priming following
      mucosal immunization.
AB  - Accumulating evidence suggests that the dichotomy between tolerance and active
      IgA immunity in mucosal immune responses is regulated at the APC level.
      Therefore, immunomodulation of the APC could be an effective mechanism to control
      the two response patterns. In this study, we demonstrate that ADP-ribosylation
      controls the outcome of tolerance or active effector T cell immunity to an
      internal peptide p323-339 from OVA inserted into the cholera toxin (CT)-derived
      CTA1-OVA-DD adjuvant. We found that a single point mutation, CTA1R7K-OVA-DD,
      resulting in lack of enzymatic activity, promoted peptide-specific tolerance in
      TCR transgenic CD4(+) T cells following a single intranasal (i.n.) treatment. The
      CTA1R7K-OVA-DD-induced tolerance was strong, long-lasting, and impaired the
      ability of adoptively transferred naive peptide-specific CD4(+) T cells to
      respond to Ag-challenge, irrespective if this was given i.p or i.n. The tolerance
      correlated with induction of regulatory T cells of the regulatory T type 1
      characterized by CD25(-)Foxp3(-)CD4(+) T cells producing IL-10. In contrast, in
      IL-10-deficient mice, no peptide-specific tolerance was observed, and these mice
      exhibited unimpaired CD4(+) T cell responsiveness to recall Ag irrespective of if
      they were untreated (PBS) or treated i.n. with CTA1R7K-OVA-DD. Thus, for the
      first time, we can provide unequivocal proof that ADP-ribosylation can control
      the outcome of mucosal Ag exposure from tolerance to an enhanced effector CD4(+)
      T cell response. The exploitation of this system for clinical treatment of
      autoimmune diseases is discussed.

PMID- 20142364
TI  - Urokinase receptor is necessary for bacterial defense against pneumonia-derived
      septic melioidosis by facilitating phagocytosis.
AB  - Urokinase receptor (urokinase-type plasminogen activator receptor [uPAR], CD87),
      a GPI-anchored protein, is considered to play an important role in inflammation
      and fibrinolysis. The Gram-negative bacterium Burkholderia pseudomallei is able
      to survive and replicate within leukocytes and causes melioidosis, an important
      cause of pneumonia-derived community-acquired sepsis in Southeast Asia. In this
      study, we investigated the expression and function of uPAR both in patients with
      septic melioidosis and in a murine model of experimental melioidosis. uPAR mRNA
      and surface expression was increased in patients with septic melioidosis in/on
      both peripheral blood monocytes and granulocytes as well as in the pulmonary
      compartment during experimental pneumonia-derived melioidosis in mice. uPAR
      deficient mice intranasally infected with B. pseudomallei showed an enhanced
      growth and dissemination of B. pseudomallei when compared with wild-type mice,
      corresponding with increased pulmonary and hepatic inflammation. uPAR knockout
      mice demonstrated significantly reduced neutrophil migration toward the pulmonary
      compartment after inoculation with B. pseudomallei. Further in vitro experiments
      showed that uPAR-deficient macrophages and granulocytes display a markedly
      impaired phagocytosis of B. pseudomallei. Additional studies showed that uPAR
      deficiency did not influence hemostatic and fibrinolytic responses during severe
      melioidosis. These data suggest that uPAR is crucially involved in the host
      defense against sepsis caused by B. pseudomallei by facilitating the migration of
      neutrophils toward the primary site of infection and subsequently facilitating
      the phagocytosis of B. pseudomallei.

PMID- 20142366
TI  - Singleton pregnancies' outcomes were compared when oocytes and embryos were
      cultured in two different commercially available sequential culture media.

PMID- 20142363
TI  - In vivo role of Flt3 ligand and dendritic cells in NK cell homeostasis.
AB  - IL-15 is required for NK cell development and homeostasis in vivo. Because IL-15
      is presented in trans via its high-affinity IL-15Ralpha-chain to cells expressing
      the IL-15Rbetagamma complex, we postulated that certain IL-15-bearing cells must
      be required for NK cell homeostasis. Using IL-15(WT/WT) and IL-15(-/-) mice, bone
      marrow chimeras with normal cellularity, and a selective depletion of CD11c(hi)
      dendritic cells (DCs), we demonstrate that ablation of the resting CD11c(hi) DC
      population results in a highly significant decrease in the absolute number of
      mature NK cells. In contrast, administration of Flt3 ligand increases the
      CD11c(hi) DC population, which, when expressing IL-15, significantly expands
      mature NK cells via enhanced survival and proliferation. In summary, a CD11c(hi)
      DC population expressing IL-15 is required to maintain NK cell homeostasis under
      conditions of normal cellularity and also is required to mediate Flt3 ligand
      induced NK cell expansion in vivo.

PMID- 20142365
TI  - In vivo imaging of an inducible oncogenic tumor antigen visualizes tumor
      progression and predicts CTL tolerance.
AB  - Visualizing oncogene/tumor Ag expression by noninvasive imaging is of great
      interest for understanding processes of tumor development and therapy. We
      established transgenic (Tg) mice conditionally expressing a fusion protein of the
      SV40 large T Ag and luciferase (TagLuc) that allows monitoring of oncogene/tumor
      Ag expression by bioluminescent imaging upon Cre recombinase-mediated activation.
      Independent of Cre-mediated recombination, the TagLuc gene was expressed at low
      levels in different tissues, probably due to the leakiness of the stop cassette.
      The level of spontaneous TagLuc expression, detected by bioluminescent imaging,
      varied between the different Tg lines, depended on the nature of the Tg
      expression cassette, and correlated with Tag-specific CTL tolerance. Following
      liver-specific Cre-loxP site-mediated excision of the stop cassette that
      separated the promoter from the TagLuc fusion gene, hepatocellular carcinoma
      development was visualized. The ubiquitous low level TagLuc expression caused the
      failure of transferred effector T cells to reject Tag-expressing tumors rather
      than causing graft-versus-host disease. This model may be useful to study
      different levels of tolerance, monitor tumor development at an early stage, and
      rapidly visualize the efficacy of therapeutic intervention versus potential side
      effects of low-level Ag expression in normal tissues.

PMID- 20142367
TI  - Diagnostic accuracy of free and total metanephrines in plasma and fractionated
      metanephrines in urine of patients with pheochromocytoma.
AB  - BACKGROUND: Plasma free and urinary metanephrines are recognized biomarkers for
      the assessment of pheochromocytoma. Plasma total metanephrines with a long half
      life may represent another useful biomarker. OBJECTIVE: The aim of this study is
      to evaluate the diagnostic performances of plasma total metanephrines alone or
      combined with free metanephrines and fractionated 24-h urinary metanephrines.
      METHODS: A retrospective, case-control diagnostic test study was conducted
      between 1999 and 2007 in two university hospitals in Switzerland and two
      institutions in France. The patients included 46 cases with histologically proven
      pheochromocytoma, and 181 controls suspected of tumor with negative
      investigations and 3-year follow-up. None had renal dysfunction. Sensitivity and
      specificity were compared after expressing each measurement result as a ratio
      over its upper reference limit, adding the ratios of normetanephrine and
      metanephrine, and defining cut-off values of 1 or 2 for this sum. RESULTS:
      Applying a cut-off value of 1, plasma free and total metanephrines and urinary
      fractionated metanephrines had similar sensitivities of 96% (95% confidence
      interval, 86-99%), 95% (85-99%), and 95% (84-99%) along with similar
      specificities of 89% (83-94%), 91% (84-95%), and 86% (80-91%). A cut-off of 2 for
      the sum of ratios over reference limit improves the specificity, and it can be
      used for a confirmation test based on another biomarker taken among the three
      biomarkers. CONCLUSION: All three metanephrine-based tests perform equivalently
      for diagnosing pheochromocytoma in the absence of renal insufficiency, and can be
      conveniently associated two by two for confirming/excluding tumor.

PMID- 20142368
TI  - Dexamethasone suppression test predicts later development of an impaired adrenal
      function after a 14-day course of prednisone in healthy volunteers.
AB  - BACKGROUND: Suppression of the adrenal function after glucocorticoid treatment is
      common, potentially dangerous, and unpredictable. Identification of patients at
      risk is of clinical importance. We hypothesized that the dexamethasone
      suppression test predicts the development of corticosteroid-induced impaired
      adrenal function. METHODS: We included 39 healthy male volunteers. After a 1
      microg ACTH test, all participants underwent an overnight 0.5-mg dexamethasone
      suppression test. Participants then took prednisone, 0.5 mg/kg body weight, for
      14-day. After the withdrawal of prednisone, a 1-microg ACTH test was performed
      and a clinical score was assessed on days 1, 3, 7, and 21. RESULTS: On days 1, 3,
      7, and 21, 100, 50, 26.5 and 32.4% of the participants had a suppressed adrenal
      function. The risk of developing suppressed adrenal function decreased from 44 to
      0% in patients with cortisol levels after the administration of dexamethasone in
      the lowest and highest quartiles respectively. Receiver operating curve (ROC)
      analysis performed to predict a suppressed adrenal function on day 7 after the
      withdrawal of prednisone showed an area under the curve (AUC) of 0.76 (95%
      confidence interval (CI) 0.58-0.89) for cortisol after the administration of
      dexamethasone, which was in the range of the AUC of 0.78 (95% CI 0.6-0.9) for pre
      intervention cortisol after the administration of ACTH. Basal cortisol before
      intake of prednisone (AUC 0.62 (95% CI 0.44-0.78)) and the clinical score (AUC
      0.64 (95% CI 0.45-0.79)) had significantly lower AUCs. CONCLUSION: Circulating
      cortisol levels after a dexamethasone suppression test and a pre-intervention
      stimulated cortisol level are predictive of later development of a suppressed
      adrenal function after a 14-day course of prednisone, and are superior to a
      clinical score or basal cortisol levels. This may allow a more targeted concept
      for the need of stress prophylaxis after cessation of steroid therapy.

PMID- 20142369
TI  - Getting a grip on aging.

PMID- 20142371
TI  - CATCH: a clinical decision rule for the use of computed tomography in children
      with minor head injury.
AB  - BACKGROUND: There is controversy about which children with minor head injury need
      to undergo computed tomography (CT). We aimed to develop a highly sensitive
      clinical decision rule for the use of CT in children with minor head injury.
      METHODS: For this multicentre cohort study, we enrolled consecutive children with
      blunt head trauma presenting with a score of 13-15 on the Glasgow Coma Scale and
      loss of consciousness, amnesia, disorientation, persistent vomiting or
      irritability. For each child, staff in the emergency department completed a
      standardized assessment form before any CT. The main outcomes were need for
      neurologic intervention and presence of brain injury as determined by CT. We
      developed a decision rule by using recursive partitioning to combine variables
      that were both reliable and strongly associated with the outcome measures and
      thus to find the best combinations of predictor variables that were highly
      sensitive for detecting the outcome measures with maximal specificity. RESULTS:
      Among the 3866 patients enrolled (mean age 9.2 years), 95 (2.5%) had a score of
      13 on the Glasgow Coma Scale, 282 (7.3%) had a score of 14, and 3489 (90.2%) had
      a score of 15. CT revealed that 159 (4.1%) had a brain injury, and 24 (0.6%)
      underwent neurologic intervention. We derived a decision rule for CT of the head
      consisting of four high-risk factors (failure to reach score of 15 on the Glasgow
      coma scale within two hours, suspicion of open skull fracture, worsening headache
      and irritability) and three additional medium-risk factors (large, boggy hematoma
      of the scalp; signs of basal skull fracture; dangerous mechanism of injury). The
      high-risk factors were 100.0% sensitive (95% CI 86.2%-100.0%) for predicting the
      need for neurologic intervention and would require that 30.2% of patients undergo
      CT. The medium-risk factors resulted in 98.1% sensitivity (95% CI 94.6%-99.4%)
      for the prediction of brain injury by CT and would require that 52.0% of patients
      undergo CT. INTERPRETATION: The decision rule developed in this study identifies
      children at two levels of risk. Once the decision rule has been prospectively
      validated, it has the potential to standardize and improve the use of CT for
      children with minor head injury.

PMID- 20142372
TI  - Handgrip strength and mortality in the oldest old population: the Leiden 85-plus
      study.
AB  - BACKGROUND: Poor muscular strength has been shown to be associated with increased
      morbidity and mortality in diverse samples of middle-aged and elderly people.
      However, the oldest old population (i.e., over 85 years) is underrepresented in
      such studies. Our objective was to assess the association between muscular
      strength and mortality in the oldest old population. METHODS: We included 555
      participants (65% women) from the Leiden 85-plus study, a prospective population
      based study of all 85-year-old inhabitants of Leiden, Netherlands. We measured
      the handgrip strength of participants at baseline and again at age 89 years. We
      collected baseline data on comorbidities, functional status, levels of physical
      activity, and adjusted for potential confounders. During the follow-up period, we
      collected data on mortality. RESULTS: During a follow-up period of 9.5 years
      (range 8.5-10.5 years), 444 (80%) participants died. Risk for all-cause mortality
      was elevated among participants in the lowest tertile of handgrip strength at age
      85 years (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.00-1.82, p =
      0.047) and the lowest two tertiles of handgrip strength at age 89 years (HR 2.04,
      CI 1.24-3.35, p = 0.005 and HR 1.73, CI 1.11-2.70, p = 0.016). We also observed
      significantly increased mortality among participants in the tertile with the
      highest relative loss of handgrip strength over four years (HR 1.72, CI 1.07
      2.77, p = 0.026). INTERPRETATION: Handgrip strength, a surrogate measurement of
      overall muscular strength, is a predictor of all-cause mortality in the oldest
      old population and may serve as a convenient tool for prognostication of
      mortality risk among elderly people.

PMID- 20142373
TI  - Giant right atrium with severe pulmonary hypertension.

PMID- 20142375
TI  - Tough choices: private sale of drugs in public hospitals.

PMID- 20142374
TI  - Erectile dysfunction.

PMID- 20142377
TI  - American health care reformers in search of a second wind.

PMID- 20142376
TI  - Lancet retracts 12-year-old article linking autism to MMR vaccines.

PMID- 20142378
TI  - Canada lags behind United States in drug return, reuse and recycling programs.

PMID- 20142379
TI  - Medical services at the Olympics: a monumental challenge.

PMID- 20142380
TI  - Dengue fever on the rise at tourist getaways.

PMID- 20142381
TI  - What is bizarre in bizarre delusions? A critical review.
AB  - Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV)
      treats the presence of bizarre delusions (BD) as the heaviest-weighted clinical
      criterion of schizophrenia. Although BD play a major role in contemporary
      diagnostic systems, only a few empirical studies explore this issue. These
      studies provide highly heterogenous results because they are based on different
      experimental paradigms, in terms of definition, clinical sample, and number of
      raters. Here, we first discuss the psychopathological sources of the concept of
      BD, which were initially described as either nonsensical or incomprehensible.
      Then, we provide a critical review of contemporary studies on the reliability of
      BD and their methodological and conceptual limitations. Current approaches have
      focused intensely on BD's reliability and have defined BD strictly in terms of
      delusional content--mainly in terms of the physical impossibility or the cultural
      or historical incomprehensibility of the delusional claims. These approaches have
      neglected formal features of experience that underlie BD and the crucial issue of
      the nature and validity of BD. In the discussion, we argue that clinical
      diagnosis of BD cannot be limited to delusional contents alone and requires
      taking into account the subjective side of BD (how altered experience manifests
      itself) as well as the conditions of intersubjective encounter (how BD are
      expressed to and experienced by the clinician). The notion of "bizarreness" in
      schizophrenia is not purely theoretical; it has practical relevance for the
      therapeutic encounter and implications on further empirical research and on
      diagnostic approaches.

PMID- 20142385
TI  - High cost, dubious benefit.

PMID- 20142386
TI  - Where are the drugs from?

PMID- 20142387
TI  - Why didn't it work?

PMID- 20142388
TI  - Caring for Canada's children.

PMID- 20142389
TI  - Doing good in small ways.

PMID- 20142390
TI  - Bridging the gaps.

PMID- 20142391
TI  - What did the doctor say?

PMID- 20142392
TI  - Prediction versus prognosis.

PMID- 20142393
TI  - Implement research faster.

PMID- 20142394
TI  - Irregular heavy drinking occasions and risk of ischemic heart disease: a
      systematic review and meta-analysis.
AB  - Contrary to a cardioprotective effect of moderate regular alcohol consumption,
      accumulating evidence points to a detrimental effect of irregular heavy drinking
      occasions (>60 g of pure alcohol or > or =5 drinks per occasion at least monthly)
      on ischemic heart disease risk, even for drinkers whose average consumption is
      moderate. The authors systematically searched electronic databases from 1980 to
      2009 for case-control or cohort studies examining the association of irregular
      heavy drinking occasions with ischemic heart disease risk. Studies were included
      if they reported either a relative risk estimate for intoxication or frequency of
      > or =5 drinks stratified by or adjusted for total average alcohol consumption.
      The search identified 14 studies (including 31 risk estimates) containing 4,718
      ischemic heart disease events (morbidity and mortality). Using a standardized
      protocol, the authors extracted relative risk estimates and their variance, in
      addition to study characteristics. In a random-effects model, the pooled relative
      risk of irregular heavy drinking occasions compared with regular moderate
      drinking was 1.45 (95% confidence interval: 1.24, 1.70), with significant between
      study heterogeneity (I(2) = 53.9%). Results were robust in several sensitivity
      analyses. The authors concluded that the cardioprotective effect of moderate
      alcohol consumption disappears when, on average, light to moderate drinking is
      mixed with irregular heavy drinking occasions.

PMID- 20142395
TI  - Re: "cross-sectional and longitudinal associations between objectively measured
      sleep duration and body mass index: the Cardia Sleep Study".

PMID- 20142397
TI  - Low level of adjustment latitude--a risk factor for sickness absence.
AB  - BACKGROUND: The prerequisite for obtaining sickness benefit is reduced work
      ability for medical reasons in combination with work demands which cannot be
      adjusted accordingly. The aim of this study was to investigate if low levels of
      adjustment latitude, defined as the possibility to temporarily adjust work
      demands in case of ill health, influence sickness absence. METHODS: A prospective
      cohort study of 1420 employees (47% participation, aged 19-68; 56% women) was
      conducted at six Swedish workplaces. Exposure to two general and nine specific
      types of adjustment latitude was ascertained at baseline. Outcome was defined as
      the first new employer-reported sick-leave spell during a follow-up of 3-12
      months. Hazard ratios (HR) of sick leave, with 95% confidence intervals (CI),
      were estimated by Cox proportional hazards regression. RESULTS: The incidence of
      sickness absence was 2.85/1000 person-days. The self-reported reasons for sick
      leave were mainly minor complaints such as colds, influenzas and headaches.
      Employees lacking adjustment latitude had an adjusted HR of sickness absence of
      1.51 (95% CI 1.08-2.11). Among specific adjustment latitude types, those not
      having the possibility to work from home generated an HR of 1.86 (95% CI 1.31
      2.64). The effects of lack of adjustment latitude were similar for men and women
      but seemed to vary between different occupations. CONCLUSION: A low level of
      adjustment latitude at work is a risk factor for sickness absence.

PMID- 20142396
TI  - Biomarkers of systemic inflammation and risk of incident, symptomatic benign
      prostatic hyperplasia: results from the prostate cancer prevention trial.
AB  - The authors conducted a nested case-control study of serum inflammatory markers
      and risk of symptomatic benign prostatic hyperplasia (BPH), using data from the
      placebo arm of the Prostate Cancer Prevention Trial (1993-2003). Incident BPH (n
      = 676) was defined as treatment, report of 2 International Prostate Symptom Score
      (IPSS) values >14, or 2 increases of > or = 5 from baseline values with at least
      one value > or = 12. Controls (n = 683) were men who reported no BPH treatment or
      IPSS values >7 over the 7-year trial. Baseline serum was analyzed for C-reactive
      protein, tumor necrosis factor alpha (monomer), soluble tumor necrosis factor
      receptors I and II (sTNF-RI and sTNF-RII), interleukin 6, and interferon gamma.
      Controlled for age and race, a high C-reactive protein concentration was
      associated with increased BPH risk (for quartile 4 vs. quartile 1, odds ratio
      (OR) = 1.40, 95% confidence interval (CI): 1.04, 1.88); this was attenuated after
      control for body mass index (OR = 1.30, 95% CI: 0.95, 1.75). Low sTNF-RII and
      high interleukin 6 concentrations were associated with increased BPH risk (for
      quartile 4 vs. quartile 1, sTNF-RII: OR = 0.61, 95% CI: 0.46, 0.82; interleukin
      6: OR = 1.79, 95% CI: 1.32, 2.42); these associations were only in men aged <65
      years. Results suggest that systemic inflammation or lower levels of soluble
      receptors that bind inflammatory cytokines increase BPH risk.

PMID- 20142398
TI  - Ability to pay and equity in access to Italian and British National Health
      Services.
AB  - BACKGROUND: Equity in delivery and distribution of health care is an important
      determinant of health and a cornerstone in the long way to social justice. We
      performed a comparative analysis of the prevalence of Italian and British
      residents who have fully paid out-of-pocket for health services which they could
      have obtained free of charge or at a lower cost from their respective National
      Health Services. METHODS: Cross-sectional study based on a standardized
      questionnaire survey carried out in autumn 2006 among two representative samples
      (n = 1000) of the general population aged 20-74 years in each of the two
      countries. RESULTS: 78% (OR 19.9; 95% CI 15.5-25.6) of Italian residents have
      fully paid out-of-pocket for at least one access to health services in their
      lives, and 45% (OR 18.1; 95% CI 12.9-25.5) for more than five accesses.
      Considering only the last 2 years, 61% (OR 16.5; 95% CI 12.6-21.5) of Italians
      have fully paid out-of-pocket for at least one access. The corresponding pattern
      for British residents is 20 and 4% for lifelong prevalence, and 10% for the last
      2 years. CONCLUSIONS: Opening the public health facilities to a privileged
      private access to all hospital physicians based on patient's ability to pay, as
      Italy does, could be a source of social inequality in access to care and could
      probably represent a major obstacle to decreasing waiting times for patients in
      the standard formal 'free of charge' way of access.

PMID- 20142399
TI  - Relation between physical activity and blood pressure levels in young Greek
      adolescents: the Leontio Lyceum Study.
AB  - BACKGROUND: Elevated blood pressure (BP) during childhood and adolescence is not
      so rare and increases the risk of hypertension in adulthood. Physical activity
      (PA) is considered a key component for the prevention and treatment of
      hypertension in children and adolescents. Thus, the purpose of our study was to
      assess the level of PA in Greek adolescents and its relation to BP levels.
      METHODS: The study included 496 students aged 12-17 years who were enrolled on a
      volunteer basis. All children were subjected to BP measurement on two different
      occasions during a routine school day. Demographic, socio-economic and lifestyle
      characteristics were assessed by means of a standard questionnaire. Information
      on the frequency and duration of PA and on the amount of time spent on sedentary
      activities was obtained by the short-form self-administered questionnaire
      International Physical Activity Questionnaire-IPAQ. RESULTS: The study population
      was divided in three groups according to the score achieved in IPAQ
      questionnaire: low PA (n = 39), moderate PA (n = 230) and high PA (n = 231).
      Children with high PA compared to those with low PA exhibited higher systolic BP
      and pulse pressure levels, greater prevalence of prehypertension/hypertension
      status, while heart rate was significantly lower as the level of PA rose (P <
      0.05 for all cases). Intense PA was positively correlated to systolic BP (r =
      0.139, P = 0.003) and pulse pressure (r = 0.22, P = 0.0001). CONCLUSION: Intense
      PA is associated with higher systolic BP, pulse pressure levels and lower heart
      rate in healthy young adolescents. PA should be practiced at a moderate intensity
      level in everyday life.

PMID- 20142400
TI  - The epidemiology of road traffic injuries in the Republic of Lithuania, 1998
      2007.
AB  - BACKGROUND: This article highlights the epidemiology of road traffic injury (RTI)
      in Lithuania between 1998 and 2007. The purpose of this study is to explore the
      incidence of RTI, age-standardized mortality rates (ASMR), gender-specific rates
      and the RTI profile of different user groups. In doing so, this analysis attempts
      to emphasize the need for RTI prevention policies and programmes. METHODS: Six
      databases were analysed using ICD-10 codes V01-V99, pertaining to the causes of
      road traffic crashes. Data between 1998 and 2007 were obtained from these
      databases to identify and calculate RTI incidence and mortality rates. This was
      then analysed with regard to ASMR, gender, user groups and the use of alcohol.
      RESULTS: In 2007, RTI incidence in Lithuania was reported as 270/100,000 people,
      10.7% higher than in 1998. ASMR declined from 28 deaths per 100,000 in 1998 to 25
      deaths per 100,000 in 2007. Between 1998 and 2007, the male ASMR declined from 46
      to 40 deaths per 100,000 and the female ASMR decreased from 13 to 11 deaths per
      100,000. Car occupant and pedestrian fatalities comprised 87% of all RTI deaths.
      Thirty-four percent of those injured and 21% of the dead were under influence of
      alcohol. CONCLUSIONS: From 1998 to 2007, the incidence of RTI has worsened and
      mortality rates remain high in Lithuania. Alcohol remains a prominent risk factor
      of traffic injury and death. The need to develop effective prevention programmes
      to address traffic injury is essential.

PMID- 20142401
TI  - The assessment of efforts to return to work in the European Union.
AB  - BACKGROUND: Assessment of efforts to promote return-to-work (RTW) includes all
      efforts (vocational and non-vocational) designed to improve the work ability of
      the sick-listed employee and increase the chance to return to work. Aim of the
      study was to investigate whether in 13 European countries these RTW efforts are
      assessed and to compare the procedures by means of six criteria. METHODS: Data
      were gathered in the taxonomy project of the European Union of Medicine in
      Assurance and Social Security and by means of an additional questionnaire.
      RESULTS: In seven countries RTW efforts are subject of the assessment in relation
      to the application for disability benefits. Description of RTW efforts is a
      prerequisite in five countries. Guidelines on the assessment of RTW efforts are
      only available in the Netherlands and no countries report the use of the ICF
      model. Based on the results of the additional questionnaire, the assessor is a
      social scientist or a physician. The information used to assess RTW efforts
      differs, from a report on the RTW process to medical information. A negative
      outcome of the assessment leads to delay of the application for disability
      benefits or to application for rehabilitation subsidy. CONCLUSION: RTW efforts
      are assessed in half of the participating European countries. When compared, the
      characteristics of the assessment of RTW efforts in the participating European
      countries show both similarities and differences. This study may facilitate the
      gathering and exchange of knowledge and experience between countries on the
      assessment of RTW efforts.

PMID- 20142402
TI  - Relationships between job satisfaction, intentions to leave family practice and
      actually leaving among family physicians in England.
AB  - BACKGROUND: A national survey of family physicians working in the National Health
      Service (NHS) of England in 2001 revealed that 1/10 under 50 years of age were
      intending to leave direct patient care within 5 years, and that the principal
      predictor of their intention to leave was job satisfaction. Our research
      addressed two questions. First, does a family physician's stated intention to
      leave their job predict whether or not they actually do leave? Second, to what
      extent does job satisfaction predict actually leaving? METHODS: Secondary data
      analysis was performed on 1174 family physicians aged 50 years and under, who
      responded to the aforementioned survey. Using data from the annual census of
      physicians in the NHS, we determined which physicians actually left family
      practice during the next 5 years. RESULTS: Of the 1174 family physicians studied,
      194 (16.5%) had left direct patient care within 5 years. Multivariate regression
      showed that job satisfaction predicted a physician's intention to leave direct
      patient care and that intention to leave predicted actually leaving. Logically,
      job satisfaction should then have predicted actual leaving. Our findings,
      however, suggest that this is only partly true. CONCLUSION: Although higher
      levels of job 'dissatisfaction' were associated with an increased likelihood of
      leaving, higher levels of job 'satisfaction' did not prevent leaving.

PMID- 20142403
TI  - Exploring the causes of adverse events in hospitals and potential prevention
      strategies.
AB  - OBJECTIVES: To examine the causes of adverse events (AEs) and potential
      prevention strategies to minimise the occurrence of AEs in hospitalised patients.
      METHODS: For the 744 AEs identified in the patient record review study in 21
      Dutch hospitals, trained reviewers were asked to select all causal factors that
      contributed to the AE. The results were analysed together with data on
      preventability and consequences of AEs. In addition, the reviewers selected one
      or more prevention strategies for each preventable AE. The recommended prevention
      strategies were analysed together with four general causal categories: technical,
      human, organisational and patient-related factors. RESULTS: Human causes were
      predominantly involved in the causation of AEs (in 61% of the AEs), 61% of those
      being preventable and 13% leading to permanent disability. In 39% of the AEs,
      patient-related factors were involved, in 14% organisational factors and in 4%
      technical factors. Organisational causes contributed relatively often to
      preventable AEs (93%) and AEs resulting in permanent disability (20%).
      Recommended strategies to prevent AEs were quality assurance/peer review,
      evaluation of safety behaviour, training and procedures. For the AEs with human
      and patient-related causes, reviewers predominantly recommended quality
      assurance/peer review. AEs caused by organisational factors were considered
      preventable by improving procedures. DISCUSSION: Healthcare interventions
      directed at human causes are recommended because these play a large role in AE
      causation. In addition, it seems worthwhile to direct interventions on
      organisational causes because the AEs they cause are nearly always believed to be
      preventable. Organisational factors are thus relatively easy to tackle. Future
      research designs should allow researchers to interview healthcare providers that
      were involved in the event, as an additional source of information on
      contributing factors.

PMID- 20142404
TI  - A framework for measuring quality and promoting accountability across silos: the
      case of mental disorders and co-occurring conditions.
AB  - BACKGROUND: Quality measures can be effective tools for improving delivery of
      care and patient outcomes. Co-occurring conditions (COCs), including general
      medical conditions and substance use disorders, are the rule rather than the
      exception in patients with serious mental health disorders and lead to
      substantial morbidity and mortality burden. COCs among persons with mental health
      disorders are often treated by separate systems ("silos") in the US healthcare
      system, making it difficult to establish expectations for performance, assign
      accountability for measure results and ultimately improve quality of care for
      this group. OBJECTIVES: A framework for measuring quality of care for COCs is
      proposed by reviewing the current state of quality for COCs and examples of
      quality measures based on the Donabedian model. METHODS AND FRAMEWORK: The
      framework will also be applied to better define which providers are accountable
      for quality improvement, to ultimately ensure that quality measures have an
      impact on improving care for COCs.

PMID- 20142405
TI  - Patients' perceptions of early supported discharge for chronic obstructive
      pulmonary disease: a qualitative study.
AB  - OBJECTIVE: To explore patients' views of an early supported discharge service for
      chronic obstructive pulmonary disease (COPD). INTERVENTION: Early supported
      discharge service (EDS) with discharge at 3.5 days (average length of stay for
      COPD at the time was 9.5 days). After discharge, patients were visited at home
      daily for 3 days by a nurse from the early discharge service and then, as
      required, up to 2 weeks. PARTICIPANTS: Purposive, maximum variation sample of 23
      mainly older, retired patients admitted to hospital with an acute exacerbation of
      COPD in 2005. 14 patients listed as receiving EDS, and 9 listed as refusing EDS.
      DESIGN: Qualitative analysis of audiotaped, semistructured, face-to-face
      interviews. Setting Economically deprived inner-city borough in England. Results
      (1) Negotiation and consent. Patients had little recall of being approached to
      join the scheme. They often felt they had been discharged from hospital before
      they were ready. They were often unable or unwilling to negotiate timing of
      discharge with hospital staff. (2) Process of discharge from hospital. Patients
      experienced difficulties with transport home and supplies of medication. (3) Life
      at home after a hospital admission. Resuming life at home after an admission for
      an acute exacerbation for COPD was difficult. Not all patients found the home
      nursing component of the service helpful. CONCLUSIONS: Early supported discharge
      with domiciliary care is a model that ought to promote a more equal partnership
      between patient and healthcare, but this did not appear to be the case in
      practice.

PMID- 20142406
TI  - Sex differences in operating room care giver perceptions of patient safety: a
      pilot study from the Veterans Health Administration Medical Team Training
      Program.
AB  - BACKGROUND: Achieving a culture of safety is believed to be an important
      mechanism for improving patient safety. The Safety Attitudes Questionnaire (SAQ)
      measures provider perceptions of patient safety culture across six domains;
      higher scores denote more positive perceptions. Although professional differences
      on the SAQ have been explored, sex differences have not. METHODS: The SAQ was
      administered to operating room (OR) care givers at nine Department of Veterans
      Affairs hospitals. We determined the mean domain scores by care giver profession
      and sex, used analysis of variance to compare mean scores across professions,
      used t tests to compare mean scores between sexes and created regression models
      of the six patient safety domains. RESULTS: The SAQ was completed by 187 OR care
      givers. Older care givers were significantly more likely to report favourable
      perceptions of teamwork climate; surgeons were significantly more likely to
      report favourable perceptions of working conditions; anaesthesia providers were
      significantly more likely to report favourable perceptions of stress recognition
      but also less favourable perceptions of safety climate. Women were significantly
      more likely to report less favourable perceptions of job satisfaction and working
      conditions. CONCLUSION: This pilot study confirms previously reported profession
      differences in OR care giver patient safety attitudes. We also found previously
      unreported sex differences. Educational efforts designed to enhance patient
      safety should be designed so that they address such differences.

PMID- 20142407
TI  - Skillful anticipation: maternity nurses' perspectives on maintaining safety.
AB  - OBJECTIVE: To describe maternity nurses' perspectives on how they contribute to
      safety during labour and birth at two urban academic medical centres in the
      United States. DESIGN: Grounded theory: data were collected using semistructured,
      open-ended interviews and participant observations with registered nurses (RNs)
      in two inpatient maternity settings. Data were analysed simultaneously using
      constant comparison, and dimensional and situational analysis. PARTICIPANTS:
      Purposive sample of 12 RNs working in the two maternity units. FINDINGS: Safety
      was broadly conceptualised by RNs as protecting the physical, psychological and
      emotional wellbeing of a woman and her family. During labour and birth, safety
      was maintained by RNs through "skillful anticipation" of situational potential.
      This required integration of medical and technical knowledge and skill with
      intimate knowledge of the woman and the operational context of care to achieve
      accurate situation awareness and appropriate future planning. Conditions and
      processes promoting skillful anticipation included being prepared, knowing, and
      envisioning the whole picture. CONCLUSIONS: In the two settings, maternity RNs
      made active contributions to safe birth in the context of constrained resources
      through preparing the environment, anticipating potential problems and trapping
      errors before they reached the patient. The contributions of maternity nurses to
      team situation awareness and to creating safety need to be appreciated and
      administratively supported. Continued research with RNs may reveal previously
      unrecognised opportunities for safety improvements.

PMID- 20142408
TI  - A rapid admission protocol to reduce emergency department boarding times.
AB  - INTRODUCTION: Prolonged emergency department boarding times (EDBT) are associated
      with adverse clinical outcomes and longer hospital stays. A rapid admission
      protocol was designed at our institution to reduce both EDBT and time to
      admission orders (EDTAO) for patients admitted to the internal medicine service.
      METHODS: The existing admission process was examined by a team of clinical and
      administrative leaders who focused on developing a change management
      architecture, narrowing clinical roles, mandating direct communication,
      establishing clear boundaries for patient responsibility and instituting
      carefully constructed holding orders. The number of steps in the admission
      process was reduced from 50 to 10. We collected EDBT and EDTAO for all patients
      admitted to the internal medicine service before and after intervention using a
      simple interrupted time-series design. RESULTS: The study involved a total of
      9604 admissions to one of three inpatient destinations (general medicine ward,
      telemetry or intensive care unit). The overall EDBT decreased from 360 min in the
      preintervention period to 270 min in phase 4 (p<0.001). The overall time to
      admission orders decreased from 210 min in the preintervention period to 75 min
      in phase 4 (p<0.001) overall. However, no improvements were noted in EDBT for
      telemetry or ICU patients. CONCLUSIONS: Institution of a rapid admission protocol
      successfully reduced overall EDBT at our institution, although few gains were
      noted for patients with a telemetry or ICU destination. In total, the
      intervention saved 27 884 h, or 1161 emergency department patient-days, over the
      course of a single year.

PMID- 20142409
TI  - Primary thymic seminoma in a 32-year-old female.

PMID- 20142410
TI  - Long-term follow-up after risk-adapted treatment in clinical stage 1 (CS1)
      nonseminomatous germ-cell testicular cancer (NSGCT) implementing adjuvant CVB
      chemotherapy. A SWENOTECA study.
AB  - BACKGROUND: To offer minimized risk-adapted adjuvant treatment on a community and
      nationwide basis for patients with clinical stage 1 (CS1) nonseminomatous germ
      cell testicular cancer (NSGCT). The aim was to reduce the risk of relapse and
      thereby reducing the need of later salvage chemotherapy while maintaining a high
      cure rate. PATIENTS AND METHODS: From July 1995 to January 1998, a total of 232
      Swedish and Norwegian patients were treated for CS1 NSGCT. All were eligible for
      inclusion into one of two community-based multicenter Swedish and Norwegian
      Testicular Cancer Project (SWENOTECA) III studies. One study was a prospective
      randomized study for patients without vascular invasion in the testicular tumor
      (VASC-), evaluating the effect of one adjuvant course of cisplatin, vinblastine
      and bleomycin (CVB) compared with surveillance. The second study was a
      prospective study evaluating the effect of two adjuvant courses of CVB for VASC+
      patients. RESULTS: Due to slow accrual and emerging data on toxicity of CVB, the
      studies were prematurely closed for inclusion in 1998. Of the 232 CS1 patients
      treated during the study period, only 97 were included in the studies. As all
      remaining patients were managed according to the SWENOTECA III protocol, although
      not randomized, the data were pooled. At a median follow-up of 10.1 years, there
      have been 24 relapses. While one course of CVB to VASC- patients had limited
      effect on the relapse rate, two courses of adjuvant CVB reduced the relapse rate
      among VASC+ patients by >90%. Toxicity was high in patients administered adjuvant
      CVB as 24% of patients experienced grade 3 or 4 obstipation/ileus and 23% grade 3
      or 4 infection. CONCLUSIONS: There was no statistical difference in relapse rate
      between one course of adjuvant CVB and surveillance for VASC- NSGCT patients. Two
      courses of adjuvant CVB for VASC+ NSGCT patients reduced the relapse rate with
      >90% in comparison to the surveillance group. Toxicity was unacceptably high for
      all patients receiving CVB. Adjuvant CVB chemotherapy has no place in the
      treatment of CS1 NSGCT.

PMID- 20142411
TI  - Effect of natural pozzolans as mineral admixture on the performance of cemented
      paste backfill of sulphide-rich tailings.
AB  - This paper presents the effect of the natural pozzolans as mineral additives on
      the short- and long-term strength and stability performance of cemented paste
      backfill (CPB) samples. Prior to their use in CPB studies, the natural pozzolans 
      the volcanic tuffs (Akkus Trass [AT] and Fatsa Trass [FT]) and pumice (KP) -
      were tested for their pozzolanic characteristics. These tests revealed that the
      pozzolanic activity of the natural pozzolans is closely inter-related with their
      content of reactive silica and, accordingly, KP has the highest pozzolanic
      activity. The addition, or increasing the amount, of natural pozzolans in the
      binder phase resulted in a slower rate of strength development of CPB samples.
      The deterioration in stability of CPB samples prepared from Portland cement (PC)
      alone (i.e. a strength loss of 24.6%) occurred following 56 days. The replacement
      of PC with FT and AT led to even higher losses in strength. However, the addition
      of KP (up to 30 wt%) mitigated, to a certain extent, long-term strength and
      stability problems with the losses in strength of CPB samples consistently lower
      than 20%. It can be inferred that the performance of the natural pozzolans as a
      mineral additive in CPB is dependent intimately on their pozzolanic
      characteristics.

PMID- 20142412
TI  - Application of dynamic programming to evaluate the slope stability of a vertical
      extension to a balefill.
AB  - The slope-stability of a proposed vertical extension of a balefill was
      investigated in the present study, in an attempt to determine a geotechnically
      conservative design, compliant with New Jersey Department of Environmental
      Protection regulations, to maximize the utilization of unclaimed disposal
      capacity. Conventional geotechnical analytical methods are generally limited to
      well-defined failure modes, which may not occur in landfills or balefills due to
      the presence of preferential slip surfaces. In addition, these models assume an a
      priori stress distribution to solve essentially indeterminate problems. In this
      work, a different approach has been applied, which avoids several of the
      drawbacks of conventional methods. Specifically, the analysis was performed in a
      two-stage process: (a) calculation of stress distribution, and (b) application of
      an optimization technique to identify the most probable failure surface. The
      stress analysis was performed using a finite element formulation and the location
      of the failure surface was located by dynamic programming optimization method. A
      sensitivity analysis was performed to evaluate the effect of the various waste
      strength parameters of the underlying mathematical model on the results, namely
      the factor of safety of the landfill. Although this study focuses on the
      stability investigation of an expanded balefill, the methodology presented can
      easily be applied to general geotechnical investigations.

PMID- 20142413
TI  - Effect of mixture ratio, solids concentration and hydraulic retention time on the
      anaerobic digestion of the organic fraction of municipal solid waste.
AB  - This paper describes how the degradation of the organic fraction of municipal
      solid waste (OFMSW) is affected through codigestion with varying amounts of
      return activated sludge (RAS). Solid waste that had its inorganic fraction
      selectively removed was mixed with RAS in ratios of 100% OFMSW, 50% OFMSW/50%
      RAS, and 25% OFMSW/75% RAS. The total solids (TS) concentration was held at 8%
      and three anaerobic digester systems treating the mixtures were held (for the
      first run) at a total hydraulic retention time (HRT) of 28 days. Increasing
      amounts of RAS did not however improve the mixture's digestability, as indicated
      by little change and/or a drop in the main performance indices [including
      percentage volatile solids (VS) removal and specific gas production]. The optimum
      ratio in this research therefore appeared to be 100% OFMSW with an associated
      85.1 +/- 0.6% VS removal and 0.72 +/- 0.01 L total gas g(- 1) VS. In the second
      run, the effect of increasing percentage of TS (8, 12% and 15%) at a system HRT
      of 28 days was observed to yield no improvement in the main performance indices
      (i.e. percentage VS removal and specific gas production). Finally, during the
      third run, variations in the total system HRT were investigated at an 8% TS,
      again using 100% OFMSW. Of the HRTs explored (23, 28 and 33 days), the longest
      HRT yielded the best performance overall, particularly in terms of specific gas
      production (0.77 +/- 0.01 L total gas g(-1) VS).

PMID- 20142414
TI  - Implementation fidelity in adolescent family-based prevention programs:
      relationship to family engagement.
AB  - Reliability and validity of intervention studies are impossible without adequate
      program fidelity, as it ensures that the intervention was implemented as designed
      and allows for accurate conclusions about effectiveness (Bellg AJ, Borrelli B,
      Resnick B et al. Enhancing treatment fidelity in health behavior change studies:
      best practices and recommendations from the NIH behavior change consortium.
      Health Psychol 2004; 23: 443-51). This study examines the relation between
      program fidelity with family engagement (i.e. satisfaction and participation) in
      family-based prevention programs for adolescent alcohol, tobacco or other drug
      use. Families (n = 381) were those with an 11- to 12-year-old child enrolled in
      Kaiser Permanente in the San Francisco area. Families participated in one of two
      programs: Strengthening Families Program: For Parents and Youth 10-14 (SFP)
      (Spoth R, Redmond C, Lepper H. Alcohol initiation outcomes of universal family
      focused preventive interventions: one- and two-year follow-ups of a controlled
      study. J Stud Alcohol Suppl 1999; 13: 103-11) or Family Matters (FM) (Bauman KE,
      Ennett ST. On the importance of peer influence for adolescent drug use: commonly
      neglected considerations. Addiction 1996; 91: 185-98). Fidelity was assessed by:
      (i) adherence to the program manual and (ii) quality of implementation. No
      relationships were found for FM, a self-directed program. For SFP, higher quality
      scores were related to higher parent satisfaction. Higher adherence scores were
      related to higher satisfaction for youth, yet surprisingly to lower satisfaction
      for parents. Parent sessions involve much discussion, and to obtain high
      adherence scores, health educators were often required to limit this to implement
      all program activities. Findings highlight a delivery challenge in covering all
      activities while allowing parents to engage in mutually supportive behavior.

PMID- 20142415
TI  - Downregulation of Bcl-xL and Mcl-1 is sufficient to induce cell death in
      mesothelioma cells highly refractory to conventional chemotherapy.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis
      and limited response to platinum-based chemotherapy. Several lines of evidence
      support a role for the anti-apoptotic protein Bcl-x(L) in MPM chemoresistance.
      Since it has been recently suggested that Mcl-1 cooperates with Bcl-x(L) for
      protection against cell death, we investigated the response of mesothelioma cell
      lines to the downregulation of Bcl-x(L) (alone or in combination with cisplatin)
      and the potential interest of its concomitant inhibition with that of Mcl-1.
      Using RNA interference, we showed that Bcl-x(L) depletion sensitized two highly
      chemoresistant mesothelioma cell lines to cisplatin and that under this
      treatment, one cell line, MSTO-211H, displayed an apoptotic type of cell death,
      whereas the other, NCI-H28, evidenced mainly necrotic-type cell death. Otherwise,
      the inhibition of Mcl-1 by cisplatin may contribute to this induction of cell
      death observed after Bcl-x(L) downregulation. Strikingly, we observed that the
      simultaneous inhibition of Bcl-x(L) and Mcl-1 using small interfering RNA (siRNA)
      induced a massive cell death in the absence of chemotherapy and was sufficient to
      avoid escape to treatment in MSTO-211H cells. In NCI-H28, the addition of a low
      cisplatin concentration allowed to impede the long-term recovery observed after
      treatment by the siRNA combination. Together, these findings provide a strong
      molecular basis for the clinical evaluation of therapies targeting both Bcl-x(L)
      and Mcl-1, alone or in combination with conventional chemotherapy, for the
      treatment of MPM.

PMID- 20142416
TI  - Regulation of phosphate starvation responses in plants: signaling players and
      cross-talks.
AB  - Phosphate (Pi) availability is a major factor limiting growth, development, and
      productivity of plants. In both ecological and agricultural contexts, plants
      often grow in soils with low soluble phosphate content. Plants respond to this
      situation by a series of developmental and metabolic adaptations that are aimed
      at increasing the acquisition of this vital nutrient from the soil, as well as to
      sustain plant growth and survival. The development of a comprehensive
      understanding of how plants sense phosphate deficiency and coordinate the
      responses via signaling pathways has become of major interest, and a number of
      signaling players and networks have begun to surface for the regulation of the
      phosphate-deficiency response. In practice, application of such knowledge to
      improve plant Pi nutrition is hindered by complex cross-talks, which are emerging
      in the face of new data, such as the coordination of the phosphate-deficiency
      signaling networks with those involved with hormones, photo-assimilates (sugar),
      as well as with the homeostasis of other ions, such as iron. In this review, we
      focus on these cross-talks and on recent progress in discovering new signaling
      players involved in the Pi-starvation responses, such as proteins having SPX
      domains.

PMID- 20142417
TI  - Telephone-delivered Acceptance and Commitment Therapy for adult smoking
      cessation: a feasibility study.
AB  - BACKGROUND: Quitline smoking cessation counseling results in a mere 12% success
      rate. Testing of new telephone-delivered cessation counseling approaches is
      needed. OBJECTIVE: Determine the feasibility of the first telephone-delivered
      Acceptance and Commitment Therapy (ACT) intervention for smoking cessation.
      DESIGN: Fourteen adults (57% racial/ethnic minority, 8/14) in a single-arm study.
      Counselor proactively delivered a 5-session (90-min total) ACT telephone
      intervention for smoking cessation. Hypothesized ACT processes were self-reported
      at baseline and posttreatment. Smoking status was self-reported at baseline, 20
      day posttreatment (93% retention, 13/14), and 12-month posttreatment (93%
      retention, 13/14). RESULTS: (a) Delivery length and duration: average of 3.5
      calls and 81.9-min intervention duration. (b) Receptivity: 100% (14/14) felt
      respected by the counselor, 86% (12/14) said that intervention was a good fit,
      and 93% (13/14) said that intervention helped them quit. (c) ACT processes: (i)
      acceptance of physical cravings, emotions, and thoughts that cue smoking
      increased from baseline to posttreatment (p = .001, p = .038, and p = .085,
      respectively) and (ii) commitment to quitting increased from baseline to
      posttreatment (p = .01). (4) Intent-to-treat cessation outcomes: (i) at 20-day
      posttreatment, 43% (6/14) had not smoked the day of the survey and 29% (4/14) had
      not smoked in past 7 days and (ii) at 12-month posttreatment, 29% (4/14) had not
      smoked at all in past 12 months. These quit rates are over double the 12% quit
      rates of current standard telephone counseling. CONCLUSION: Telephone-delivered
      ACT shows promise for smoking cessation and warrants future testing in a well
      powered randomized trial.

PMID- 20142418
TI  - Rapid automated blood sampling system for pharmacokinetics studies of cigarette
      smoking.
AB  - INTRODUCTION: We developed an automated sampling system to allow multiple,
      discrete blood samples from a human participant to be collected rapidly and
      immediately following cigarette smoke exposure. We reported the details of the
      sampling system along with the results of a pilot study for evaluation of the
      system. METHODS: Components of the system include silastic tubing, solenoid pinch
      valves, a peristaltic pump, and a fraction collector. This system incorporates a
      smoking machine that allows precise delivery of cigarette smoke through a
      mouthpiece and intricate timing to correlate blood samples with smoke inhalation.
      All components are controlled via integration from a user interface and are fully
      customizable. We performed several tests to evaluate the equipment, including
      tubing dead volume, leakage tests, and sample reproducibility. We also performed
      a pilot study with 6 adult smokers, who received 6 controlled puffs of a research
      test cigarette. Each inhalation was followed by radial arterial blood collection
      (1 sample per second tapered to 1 sample every 4 s) for 1 min. Samples were
      evaluated for nicotine via liquid chromatography-tandem mass spectrometric
      methods. RESULTS: Sampling times and volumes were sufficient for nicotine
      analysis. No adverse effects were seen in the pilot study, and a 30-min washout
      period was deemed appropriate between puffs. A significant rise in plasma
      nicotine levels above baseline after inhalation of smoke was consistently
      detected in all participants. DISCUSSION: The unique advantage of this system is
      to allow rapid blood sampling after a puff of cigarette smoke, with the benefits
      of reproducibility, reduction in labor intensity, and high temporal resolution.

PMID- 20142419
TI  - Wolf Reik: Inheritance beyond DNA. Interview by Nicole Lebrasseur.

PMID- 20142420
TI  - Tapping into the glial reservoir: cells committed to remaining uncommitted.
AB  - The development and maturation of the oligodendrocyte requires a series of highly
      orchestrated events that coordinate the proliferation and differentiation of the
      oligodendrocyte precursor cell (OPC) as well as the spatiotemporal regulation of
      myelination. In recent years, widespread interest has been devoted to the
      therapeutic potential of adult OPCs scattered throughout the central nervous
      system (CNS). In this review, we highlight molecular mechanisms controlling OPC
      differentiation during development and the implication of these mechanisms on
      adult OPCs for remyelination. Cell-autonomous regulators of differentiation and
      the heterogeneous microenvironment of the developing and the adult CNS may
      provide coordinated inhibitory cues that ultimately maintain a reservoir of
      uncommitted glia.

PMID- 20142421
TI  - Dual action of epidermal growth factor: extracellular signal-stimulated nuclear
      cytoplasmic export and coordinated translation of selected messenger RNA.
AB  - We report the first example of a coordinated dual action of epidermal growth
      factor (EGF) in stimulating the nuclear-cytoplasmic export and translation of a
      select messenger RNA (mRNA). The effect of EGF is mediated by the RNA-binding
      protein Grb7 (growth factor receptor-bound protein 7), which serves as an adaptor
      for a specific mRNA-protein export complex and a translational regulator. Using
      the kappa-opioid receptor (OR [KOR]) as a model, we demonstrate that EGF
      activates nuclear SHP-2 (Src homology region 2-containing tyrosine phosphatase),
      which dephosphorylates Grb7 in the nucleus. Hypophosphorylated Grb7 binds to the
      KOR mRNA and recruits the Hu antigen R-exportin-1 (CRM1) complex to form a
      nuclear-cytoplasmic export complex that exports KOR mRNA. EGF also activates
      focal adhesion kinase in the cytoplasm to rephosphorylate Grb7, releasing KOR
      mRNA for active translation. In summary, this study uncovers a coordinated, dual
      activity of EGF in facilitating nuclear export of a specific mRNA-protein complex
      as well as translational activation of the exported mRNA.

PMID- 20142422
TI  - SOLO: a meiotic protein required for centromere cohesion, coorientation, and SMC1
      localization in Drosophila melanogaster.
AB  - Sister chromatid cohesion is essential to maintain stable connections between
      homologues and sister chromatids during meiosis and to establish correct
      centromere orientation patterns on the meiosis I and II spindles. However, the
      meiotic cohesion apparatus in Drosophila melanogaster remains largely
      uncharacterized. We describe a novel protein, sisters on the loose (SOLO), which
      is essential for meiotic cohesion in Drosophila. In solo mutants, sister
      centromeres separate before prometaphase I, disrupting meiosis I centromere
      orientation and causing nondisjunction of both homologous and sister chromatids.
      Centromeric foci of the cohesin protein SMC1 are absent in solo mutants at all
      meiotic stages. SOLO and SMC1 colocalize to meiotic centromeres from early
      prophase I until anaphase II in wild-type males, but both proteins disappear
      prematurely at anaphase I in mutants for mei-S332, which encodes the Drosophila
      homologue of the cohesin protector protein shugoshin. The solo mutant phenotypes
      and the localization patterns of SOLO and SMC1 indicate that they function
      together to maintain sister chromatid cohesion in Drosophila meiosis.

PMID- 20142423
TI  - Synaptobrevin N-terminally bound to syntaxin-SNAP-25 defines the primed vesicle
      state in regulated exocytosis.
AB  - Rapid neurotransmitter release depends on the ability to arrest the SNAP receptor
      (SNARE)-dependent exocytosis pathway at an intermediate "cocked" state, from
      which fusion can be triggered by Ca(2+). It is not clear whether this state
      includes assembly of synaptobrevin (the vesicle membrane SNARE) to the syntaxin
      SNAP-25 (target membrane SNAREs) acceptor complex or whether the reaction is
      arrested upstream of that step. In this study, by a combination of in vitro
      biophysical measurements and time-resolved exocytosis measurements in adrenal
      chromaffin cells, we find that mutations of the N-terminal interaction layers of
      the SNARE bundle inhibit assembly in vitro and vesicle priming in vivo without
      detectable changes in triggering speed or fusion pore properties. In contrast,
      mutations in the last C-terminal layer decrease triggering speed and fusion pore
      duration. Between the two domains, we identify a region exquisitely sensitive to
      mutation, possibly constituting a switch. Our data are consistent with a model in
      which the N terminus of the SNARE complex assembles during vesicle priming,
      followed by Ca(2+)-triggered C-terminal assembly and membrane fusion.

PMID- 20142425
TI  - Terminal drought-tolerant pearl millet [Pennisetum glaucum (L.) R. Br.] have high
      leaf ABA and limit transpiration at high vapour pressure deficit.
AB  - It was previously shown that pearl millet genotypes carrying a terminal drought
      tolerance quantitative trait locus (QTL) had a lower transpiration rate (Tr; g
      cm(-2) d(-1)) under well-watered conditions than sensitive lines. Here
      experiments were carried out to test whether this relates to leaf abscisic acid
      (ABA) and Tr concentration at high vapour pressure deficit (VPD), and whether
      that leads to transpiration efficiency (TE) differences. These traits were
      measured in tolerant/sensitive pearl millet genotypes, including near-isogenic
      lines introgressed with a terminal drought tolerance QTL (NIL-QTLs). Most
      genotypic differences were found under well-watered conditions. ABA levels under
      well-watered conditions were higher in tolerant genotypes, including NIL-QTLs,
      than in sensitive genotypes, and ABA did not increase under water stress. Well
      watered Tr was lower in tolerant than in sensitive genotypes at all VPD levels.
      Except for one line, Tr slowed down in tolerant lines above a breakpoint at 1.40
      1.90 kPa, with the slope decreasing >50%, whereas sensitive lines showed no
      change in that Tr response across the whole VPD range. It is concluded that two
      water-saving (avoidance) mechanisms may operate under well-watered conditions in
      tolerant pearl millet: (i) a low Tr even at low VPD conditions, which may relate
      to leaf ABA; and (ii) a sensitivity to higher VPD that further restricts Tr,
      which suggests the involvement of hydraulic signals. Both traits, which did not
      lead to TE differences, could contribute to absolute water saving seen in part
      due to dry weight increase differences. This water saved would become critical
      for grain filling and deserves consideration in the breeding of terminal drought
      tolerant lines.

PMID- 20142424
TI  - Localized topological changes of the plasma membrane upon exocytosis visualized
      by polarized TIRFM.
AB  - Total internal reflection fluorescence microscopy (TIRFM) images the plasma
      membrane-cytosol interface and has allowed insights into the behavior of
      individual secretory granules before and during exocytosis. Much less is known
      about the dynamics of the other partner in exocytosis, the plasma membrane. In
      this study, we report the implementation of a TIRFM-based polarization technique
      to detect rapid submicrometer changes in plasma membrane topology as a result of
      exocytosis. A theoretical analysis of the technique is presented together with
      image simulations of predicted topologies of the postfusion granule membrane
      plasma membrane complex. Experiments on diI-stained bovine adrenal chromaffin
      cells using polarized TIRFM demonstrate rapid and varied submicrometer changes in
      plasma membrane topology at sites of exocytosis that occur immediately upon
      fusion. We provide direct evidence for a persistent curvature in the exocytotic
      region that is altered by inhibition of dynamin guanosine triphosphatase activity
      and is temporally distinct from endocytosis measured by VMAT2-pHluorin.

PMID- 20142426
TI  - Cancers converge at 2-HG.

PMID- 20142427
TI  - IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+
      cell subsets from Id2-dependent precursors.
AB  - The natural cytotoxicity receptor NKp46 (encoded by Ncr1) was recently shown to
      identify a subset of noncytotoxic, Rag-independent gut lymphocytes that express
      the transcription factor Rorc, produce interleukin (IL)-22, and provide innate
      immune protection at the intestinal mucosa. Intestinal CD3(-)NKp46(+) cells are
      phenotypically heterogeneous, comprising a minority subset that resembles
      classical mature splenic natural killer (NK) cells (NK1.1(+), Ly49(+)) but also a
      large CD127(+)NK1.1(-) subset of lymphoid tissue inducer (LTi)-like Rorc(+) cells
      that has been proposed to include NK cell precursors. We investigated the
      developmental relationships between these intestinal CD3(-)NKp46(+) subsets. Gut
      CD3(-)NKp46(+) cells were related to LTi and NK cells in requiring the
      transcriptional inhibitor Id2 for normal development. Overexpression of IL-15 in
      intestinal epithelial cells expanded NK1.1(+) cells within the gut but had no
      effect on absolute numbers of the CD127(+)NK1.1(-)Rorc(+) subset of CD3(
      )NKp46(+) cells. In contrast, IL-7 deficiency strongly reduced the overall
      numbers of CD3(-)NKp46(+)NK1.1(-) cells that express Rorc and produce IL-22 but
      failed to restrict homeostasis of classical intestinal NK1.1(+) cells. Finally,
      in vivo fate-mapping experiments demonstrated that intestinal NK1.1(+)CD127(-)
      cells are not the progeny of Rorc-expressing progenitors, indicating that
      CD127(+)NK1.1(-)Rorc(+) cells are not canonical NK cell precursors. These studies
      highlight the independent cytokine regulation of functionally diverse intestinal
      NKp46(+) cell subsets.

PMID- 20142428
TI  - Natural killer receptors: the burden of a name.
AB  - A population of cells that expresses the NK cell receptor NKp46 and produces
      interleukin (IL)-22 have recently attracted considerable attention. The identity
      of these cells is still the subject of speculation, being variably defined as a
      novel NK cell subset or as a population containing conventional NK (cNK) cell
      precursors. In this issue, two studies shed light on this conundrum,
      demonstrating that NKp46(+) IL-22(+) cells and cNK cells belong to distinct
      lineages.

PMID- 20142429
TI  - IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center
      responses.
AB  - During T cell-dependent responses, B cells can either differentiate
      extrafollicularly into short-lived plasma cells or enter follicles to form
      germinal centers (GCs). Interactions with T follicular helper (Tfh) cells are
      required for GC formation and for selection of somatically mutated GC B cells.
      Interleukin (IL)-21 has been reported to play a role in Tfh cell formation and in
      B cell growth, survival, and isotype switching. To date, it is unclear whether
      the effect of IL-21 on GC formation is predominantly a consequence of this
      cytokine acting directly on the Tfh cells or if IL-21 directly influences GC B
      cells. We show that IL-21 acts in a B cell-intrinsic fashion to control GC B cell
      formation. Mixed bone marrow chimeras identified a significant B cell-autonomous
      effect of IL-21 receptor (R) signaling throughout all stages of the GC response.
      IL-21 deficiency profoundly impaired affinity maturation and reduced the
      proportion of IgG1(+) GC B cells but did not affect formation of early memory B
      cells. IL-21R was required on GC B cells for maximal expression of Bcl-6. In
      contrast to the requirement for IL-21 in the follicular response to sheep red
      blood cells, a purely extrafollicular antibody response to Salmonella dominated
      by IgG2a was intact in the absence of IL-21.

PMID- 20142430
TI  - IL-21 regulates germinal center B cell differentiation and proliferation through
      a B cell-intrinsic mechanism.
AB  - Germinal centers (GCs) are sites of B cell proliferation, somatic hypermutation,
      and selection of variants with improved affinity for antigen. Long-lived memory B
      cells and plasma cells are also generated in GCs, although how B cell
      differentiation in GCs is regulated is unclear. IL-21, secreted by T follicular
      helper cells, is important for adaptive immune responses, although there are
      conflicting reports on its target cells and mode of action in vivo. We show that
      the absence of IL-21 signaling profoundly affects the B cell response to protein
      antigen, reducing splenic and bone marrow plasma cell formation and GC
      persistence and function, influencing their proliferation, transition into memory
      B cells, and affinity maturation. Using bone marrow chimeras, we show that these
      activities are primarily a result of CD3-expressing cells producing IL-21 that
      acts directly on B cells. Molecularly, IL-21 maintains expression of Bcl-6 in GC
      B cells. The absence of IL-21 or IL-21 receptor does not abrogate the appearance
      of T cells in GCs or the appearance of CD4 T cells with a follicular helper
      phenotype. IL-21 thus controls fate choices of GC B cells directly.

PMID- 20142431
TI  - Alternative end-joining catalyzes class switch recombination in the absence of
      both Ku70 and DNA ligase 4.
AB  - The classical nonhomologous end-joining (C-NHEJ) DNA double-strand break (DSB)
      repair pathway employs the Ku70/80 complex (Ku) for DSB recognition and the
      XRCC4/DNA ligase 4 (Lig4) complex for ligation. During IgH class switch
      recombination (CSR) in B lymphocytes, switch (S) region DSBs are joined by C-NHEJ
      to form junctions either with short microhomologies (MHs; "MH-mediated" joins) or
      no homologies ("direct" joins). In the absence of XRCC4 or Lig4, substantial CSR
      occurs via "alternative" end-joining (A-EJ) that generates largely MH-mediated
      joins. Because upstream C-NHEJ components remain in XRCC4- or Lig4-deficient B
      cells, residual CSR might be catalyzed by C-NHEJ using a different ligase. To
      address this, we have assayed for CSR in B cells deficient for Ku70, Ku80, or
      both Ku70 and Lig4. Ku70- or Ku80-deficient B cells have reduced, but still
      substantial, CSR. Strikingly, B cells deficient for both Ku plus Lig4 undergo CSR
      similarly to Ku-deficient B cells, firmly demonstrating that an A-EJ pathway
      distinct from C-NHEJ can catalyze CSR end-joining. Ku-deficient or Ku- plus Lig4
      deficient B cells are also biased toward MH-mediated CSR joins; but, in contrast
      to XRCC4- or Lig4-deficient B cells, generate substantial numbers of direct CSR
      joins. Our findings suggest that more than one form of A-EJ can function in CSR.

PMID- 20142432
TI  - Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage
      distinct from conventional natural killer cells.
AB  - Lymphoid tissue inducer (LTi) cells are required for lymph node formation during
      fetal development, and recent evidence implies a role in mucosal immunity in the
      adult. LTi cells share some phenotypic features of conventional natural killer
      (NK; cNK) cells; however, little is known to date about the relationship between
      these two cell types. We show that lineage(-) (Lin(-)) CD127(+)RORC(+) LTi-like
      cells in human tonsil are precursors to CD56(+)CD127(+)RORC(+)NKp46(+) cells,
      which together comprise a stable RORC(+) lineage. We find that LTi-like cells and
      their CD56(+) progeny can be expanded and cloned ex vivo without loss of function
      and without conversion into cNK cells. Clonal analysis reveals heterogeneity of
      cytokine production within the CD127(+) LTi-like population. Furthermore, we
      identify within the tonsil a cNK precursor population that is characterized as
      Lin(-)CD117(+)CD161(+)CD127(-) cells. Overall, we propose that CD127(+)RORC(+)
      cells, although they share some characteristics with cNK cells, represent a
      functionally and developmentally distinct lineage.

PMID- 20142433
TI  - Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous
      leukemia with isocitrate dehydrogenase 1 and 2 mutations.
AB  - Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), are present in most
      gliomas and secondary glioblastomas, but are rare in other neoplasms. IDH1/2
      mutations are heterozygous, and affect a single arginine residue. Recently, IDH1
      mutations were identified in 8% of acute myelogenous leukemia (AML) patients. A
      glioma study revealed that IDH1 mutations cause a gain-of-function, resulting in
      the production and accumulation of 2-hydroxyglutarate (2-HG). Genotyping of 145
      AML biopsies identified 11 IDH1 R132 mutant samples. Liquid chromatography-mass
      spectrometry metabolite screening revealed increased 2-HG levels in IDH1 R132
      mutant cells and sera, and uncovered two IDH2 R172K mutations. IDH1/2 mutations
      were associated with normal karyotypes. Recombinant IDH1 R132C and IDH2 R172K
      proteins catalyze the novel nicotinamide adenine dinucleotide phosphate (NADPH)
      dependent reduction of alpha-ketoglutarate (alpha-KG) to 2-HG. The IDH1 R132C
      mutation commonly found in AML reduces the affinity for isocitrate, and increases
      the affinity for NADPH and alpha-KG. This prevents the oxidative decarboxylation
      of isocitrate to alpha-KG, and facilitates the conversion of alpha-KG to 2-HG.
      IDH1/2 mutations confer an enzymatic gain of function that dramatically increases
      2-HG in AML. This provides an explanation for the heterozygous acquisition of
      these mutations during tumorigenesis. 2-HG is a tractable metabolic biomarker of
      mutant IDH1/2 enzyme activity.

PMID- 20142435
TI  - Similarity and agreement in self-and other perception: a meta-analysis.
AB  - The authors examined the consistency of person perception in two domains:
      agreement (i.e., do two raters of the same person agree?) and similarity (i.e.,
      does a perceiver view two persons as similar to one another?). In each domain,
      they compared self-judgments with judgments not involving the self (i.e., self
      other agreement vs. consensus, in the case of agreement, and assumed similarity
      vs. assimilation, in the case of similarity). In a meta-analysis of 24 studies,
      they examined the effects of several moderating variables on each type of
      judgment. In general, moderators exerted similar effects irrespective of whether
      judgments of the self were involved. Group size did have stronger effects on self
      other agreement and assumed similarity than on consensus and assimilation. The
      authors also present evidence that new measures of assumed similarity and self
      other agreement using the Social Relations Model seem to be relatively
      independent of the moderators.

PMID- 20142434
TI  - Mice treated with chlorpyrifos or chlorpyrifos oxon have organophosphorylated
      tubulin in the brain and disrupted microtubule structures, suggesting a role for
      tubulin in neurotoxicity associated with exposure to organophosphorus agents.
AB  - Exposure to organophosphorus (OP) agents can lead to learning and memory
      deficits. Disruption of axonal transport has been proposed as a possible
      explanation. Microtubules are an essential component of axonal transport. In
      vitro studies have demonstrated that OP agents react with tubulin and disrupt the
      structure of microtubules. Our goal was to determine whether in vivo exposure
      affects microtubule structure. One group of mice was treated daily for 14 days
      with a dose of chlorpyrifos that did not significantly inhibit
      acetylcholinesterase. Beta-tubulin from the brains of these mice was
      diethoxyphosphorylated on tyrosine 281 in peptide GSQQY(281)RALTVPELTQQMFDSK. A
      second group of mice was treated with a single sublethal dose of chlorpyrifos
      oxon (CPO). Microtubules and cosedimenting proteins from the brains of these mice
      were visualized by atomic force microscopy nanoimaging and by Coomassie blue
      staining of polyacrylamide gel electrophoresis bands. Proteins in gel slices were
      identified by mass spectrometry. Nanoimaging showed that microtubules from
      control mice were decorated with many proteins, whereas microtubules from CPO
      treated mice had fewer associated proteins, a result confirmed by mass
      spectrometry of proteins extracted from gel slices. The dimensions of
      microtubules from CPO-treated mice (height 8.7 +/- 3.1 nm and width 36.5 +/- 15.5
      nm) were about 60% of those from control mice (height 13.6 +/- 3.6 nm and width
      64.8 +/- 15.9 nm). A third group of mice was treated with six sublethal doses of
      CPO over 50.15 h. Mass spectrometry identified diethoxyphosphorylated serine 338
      in peptide NS(338)NFVEWIPNNVK of beta-tubulin. In conclusion, microtubules from
      mice exposed to chlorpyrifos or to CPO have covalently modified amino acids and
      abnormal structure, suggesting disruption of microtubule function. Covalent
      binding of CPO to tubulin and to tubulin-associated proteins is a potential
      mechanism of neurotoxicity.

PMID- 20142436
TI  - The psychedelic genes of maize redundantly promote carbohydrate export from
      leaves.
AB  - Whole-plant carbohydrate partitioning involves the assimilation of carbon in
      leaves and its translocation to nonphotosynthetic tissues. This process is
      fundamental to plant growth and development, but its regulation is poorly
      understood. To identify genes controlling carbohydrate partitioning, we isolated
      mutants that are defective in exporting fixed carbon from leaves. Here we
      describe psychedelic (psc), a new mutant of maize (Zea mays) that is perturbed in
      carbohydrate partitioning. psc mutants exhibit stable, discrete chlorotic and
      green regions within their leaves. psc chlorotic tissues hyperaccumulate starch
      and soluble sugars, while psc green tissues appear comparable to wild-type
      leaves. The psc chlorotic and green tissue boundaries are usually delineated by
      larger veins, suggesting that translocation of a mobile compound through the
      veins may influence the tissue phenotype. psc mutants display altered biomass
      partitioning, which is consistent with reduced carbohydrate export from leaves to
      developing tissues. We determined that the psc mutation is unlinked to previously
      characterized maize leaf carbohydrate hyperaccumulation mutants. Additionally, we
      found that the psc mutant phenotype is inherited as a recessive, duplicate-factor
      trait in some inbred lines. Genetic analyses with other maize mutants with
      variegated leaves and impaired carbohydrate partitioning suggest that Psc defines
      an independent pathway. Therefore, investigations into the psc mutation have
      uncovered two previously unknown genes that redundantly function to regulate
      carbohydrate partitioning in maize.

PMID- 20142437
TI  - Impact of initial pathogen density on resistance and tolerance in a polymorphic
      disease resistance gene system in Arabidopsis thaliana.
AB  - The evolution of natural enemy defense shapes evolutionary trajectories of
      natural populations. Although the intensity of selection imposed by enemies
      clearly varies among natural populations, little is known about the reaction norm
      of genotypes under a gradient of selective pressure. In this study, we measure
      the quantitative responses of disease symptoms and plant fitness to a gradient of
      infection, focusing on the gene-for-gene interaction between the Rpm1 resistance
      gene in Arabidopsis thaliana and the AvrRpm1 avirulence gene in the bacterial
      pathogen Pseudomonas syringae. Two complementary sets of plant material were
      used: resistant (R) and susceptible (S) isogenic lines and a set of six natural
      accessions, three of which are Rpm1 resistant (R) and three of which are rpm1
      susceptible (S). Nine initial pathogen densities were applied to each plant line.
      Using isogenic lines allows any differences between R and S lines to be
      attributed directly to the Rpm1 gene, whereas using natural accessions allows the
      natural variation of resistance and tolerance over a gradient of infection
      dosages within R and S accessions to be described. For both sets of plant
      material, increased infection dosage results in more extensive disease symptoms,
      with a subsequent decrease in seed production. The severity of disease symptoms
      was reduced in R relative to S subgroups, and the presence of the Rpm1 allele led
      to an increase in plant fitness. Tolerance, defined as the ability to sustain
      infection without a reduction in fitness, was directly affected by Rpm1,
      providing a novel demonstration of an R gene affecting tolerance. Genetic
      variation for tolerance was also found within the S and R natural accessions,
      suggesting the potential for selection to act upon this important trait.

PMID- 20142438
TI  - Female-biased expression on the X chromosome as a key step in sex chromosome
      evolution in threespine sticklebacks.
AB  - Given that the genome of males and females are almost identical with the
      exception of genes on the Y (or W) chromosome or sex-determining alleles (in
      organisms without sex chromosomes), it is likely that many downstream processes
      resulting in sexual dimorphism are produced by changes in regulation. In early
      stages of sex chromosome evolution, as the Y-chromosome degenerates, gene
      expression should be significantly impacted for genes residing on the sex
      chromosome pair as regulatory mutations accumulate. However, this has rarely been
      examined because most model organisms have clearly diverged sex chromosomes. Fish
      provide a unique opportunity to examine the evolution of sex chromosomes because
      genetic sex determination has evolved quite recently in some groups of fish. We
      compared sex-specific transcription in threespine stickleback (Gasterosteus
      aculeatus) liver tissue using a long-oligo microarray. Of the 1,268 genes that
      were differentially expressed between sexes, a highly significant proportion
      (23%) was concentrated on chromosome 19, corresponding to the recently described
      nascent sex chromosomes. The sex-biased genes are enriched for different
      functional categories in males and females, although there is no specific
      functional enrichment on the sex chromosomes. Female-biased genes are
      concentrated at one end of the sex chromosome, corresponding to a deletion in the
      Y, suggesting a lack of global dosage compensation. Prior research on threespine
      sticklebacks has demonstrated various degrees of dissimilarity in upstream
      regions of genes on the Y providing a potential mechanism for the observed
      patterns of female-biased expression. We hypothesize that degeneration of the Y
      chromosome results in regulatory mutations that create a sex-specific expression
      pattern and that this physical concentration of sex-biased expression on the
      nascent sex chromosome may be a key feature characterizing intermediate phases of
      sex chromosome evolution.

PMID- 20142439
TI  - Characterization of TRPC2, an essential genetic component of VNS chemoreception,
      provides insights into the evolution of pheromonal olfaction in secondary-adapted
      marine mammals.
AB  - Pheromones are chemical cues released and sensed by individuals of the same
      species, which are of major importance in regulating reproductive and social
      behaviors of mammals. Generally, they are detected by the vomeronasal system
      (VNS). Here, we first investigated and compared an essential genetic component of
      vomeronasal chemoreception, that is, TRPC2 gene, of four marine mammals varying
      the degree of aquatic specialization and related terrestrial species in order to
      provide insights into the evolution of pheromonal olfaction in the mammalian
      transition from land to water. Our results based on sequence characterizations
      and evolutionary analyses, for the first time, show the evidence for the
      ancestral impairment of vomeronasal pheromone signal transduction pathway in
      fully aquatic cetaceans, supporting a reduced or absent dependence on olfaction
      as a result of the complete adaptation to the marine habitat, whereas the
      amphibious California sea lion was found to have a putatively functional TRPC2
      gene, which is still under strong selective pressures, reflecting the reliance of
      terrestrial environment on chemical recognition among the semiadapted marine
      mammals. Interestingly, our study found that, unlike that of the California sea
      lion, TRPC2 genes of the harbor seal and the river otter, both of which are also
      semiaquatic, are pseudogenes. Our data suggest that other unknown selective
      pressures or sensory modalities might have promoted the independent absence of a
      functional VNS in these two species. In this respect, the evolution of pheromonal
      olfaction in marine mammals appears to be more complex and confusing than has
      been previously thought. Our study makes a useful contribution to the current
      understanding of the evolution of pheromone perception of mammals in response to
      selective pressures from an aquatic environment.

PMID- 20142440
TI  - Ontogenetic complexity of sexual dimorphism and sex-specific selection.
AB  - Sex-biased gene expression is becoming an increasingly important way to study
      sexual selection at the molecular genetic level. However, little is known about
      the timing, persistence, and continuity of gene expression required in the
      creation of distinct male and female phenotypes, and even less about how sex
      specific selection pressures shift over the life cycle. Here, we present a time
      series global transcription profile for autosomal genes in male and female
      chicken, beginning with embryonic development and spanning to reproductive
      maturity, for the gonad. Overall, the amount and magnitude of sex-biased
      expression increased as a function of age, though sex-biased gene expression was
      surprisingly ephemeral, with very few genes exhibiting continuous sex bias in
      both embryonic and adult tissues. Despite a large predicted role of the sex
      chromosomes in sexual dimorphism, our study indicates that the autosomes house
      the majority of genes with sex-biased expression. Most interestingly, sex
      specific evolutionary pressures shifted over the course of the life cycle, acting
      equally strongly on female-biased genes and male-biased genes but at different
      ages. Female-biased genes exhibited high rates of divergence late in embryonic
      development, shortly before arrested meiosis halts oogenesis. The level of
      divergence on female-biased late embryonic genes is similar to that seen in male
      biased genes expressed in adult gonads, which correlates with the onset of
      spermatogenesis. These analyses reveal that sex-specific selection pressure
      varies over the life cycle as a function of male and female biology.

PMID- 20142441
TI  - Adaptive evolution of foundation kinetochore proteins in primates.
AB  - Rapid evolution is a hallmark of centromeric DNA in eukaryotic genomes. Yet, the
      centromere itself has a conserved functional role that is mediated by the
      kinetochore protein complex. To broaden our understanding about both the DNA and
      proteins that interact at the functional centromere, we sought to gain a detailed
      view of the evolutionary events that have shaped the primate kinetochore.
      Specifically, we performed comparative mapping and sequencing of the genomic
      regions encompassing the genes encoding three foundation kinetochore proteins:
      Centromere Proteins A, B, and C (CENP-A, CENP-B, and CENP-C). A histone H3
      variant, CENP-A provides the foundation of the centromere-specific nucleosome.
      Comparative sequence analyses of the CENP-A gene in 14 primate species revealed
      encoded amino-acid residues within both the histone-fold domain and the N
      terminal tail that are under strong positive selection. Similar comparative
      analyses of CENP-C, another foundation protein essential for centromere function,
      identified amino-acid residues throughout the protein under positive selection in
      the primate lineage, including several in the centromere localization and DNA
      binding regions. Perhaps surprisingly, the gene encoding CENP-B, a kinetochore
      protein that binds specifically to alpha-satellite DNA, was not found to be
      associated with signatures of positive selection. These findings point to
      important and distinct evolutionary forces operating on the DNA and proteins of
      the primate centromere.

PMID- 20142442
TI  - Why do patients seek care at retail clinics, and what alternatives did they
      consider?
AB  - Retail clinics are an increasingly popular new model of ambulatory care. To
      understand why patients seek care at these clinics and what their experiences
      were like, the authors interviewed 61 patients at 6 retail clinics. Patients were
      satisfied with the overall experience and were attracted to retail clinics
      because of their convenient locations and fixed, transparent pricing. Patients
      who had a primary care physician (PCP) sought care at these clinics primarily
      because their PCPs were not available in a timely manner. If retail clinics had
      not been available, a quarter of patients report they would have gone to the
      emergency department. Retail clinics appear to be responding to the need for
      convenient, affordable, and consumer-centered care.

PMID- 20142443
TI  - Random forests classification analysis for the assessment of diagnostic skill.
AB  - Mechanisms are needed to assess learning in the context of graduate medical
      education. In general, research in this regard is focused on the individual
      learner. At the level of the group, learning assessment can also inform practice
      based learning and may provide the foundation for whole systems improvement. The
      authors present the results of a random forests classification analysis of the
      diagnostic skill of rheumatology trainees as compared with rheumatology
      attendings. A random forests classification analysis is a novel statistical
      approach that captures the strength of alignment of thinking between student and
      teacher. It accomplishes this by providing information about the strength and
      correlation of multiple variables.

PMID- 20142445
TI  - Age-related differences in characteristics, performance measures, treatment
      trends, and outcomes in patients with ischemic stroke.
AB  - BACKGROUND: Prior studies have suggested lower use of guideline-recommended
      therapy and worse poststroke outcomes in older patients. We sought to examine age
      related differences in characteristics, performance measures, temporal trends,
      and early clinical outcomes for acute ischemic stroke in a large contemporary
      cohort. METHODS AND RESULTS: The relationships between age and clinical
      characteristics, performance measures, and in-hospital outcomes were analyzed in
      502 036 ischemic stroke admissions from 1256 hospitals in the Get With the
      Guidelines-Stroke program from 2003 to 2009. Data were analyzed by age groups
      (<50, 50 to 59, 60 to 69, 70 to 79, 80 to 89, and >/=90 years) and with age as a
      continuous variable. Seven predefined performance measures and 2 summary measures
      were analyzed. Mean age of ischemic stroke patients was 71.0+/-14.6 years; 52.5%
      were women. Older patients were more likely to have a history of atrial
      fibrillation or hypertension and less likely to be black, Hispanic, or
      current/recent smokers. Although modest age-related differences in each
      individual performance measure were identified, there were substantial temporal
      improvements in performance measures from 2003 to 2009 in each age group, and
      many age-related treatment gaps were narrowed or eliminated over time. Older
      patients were less likely to be discharged home (adjusted odds ratio, 0.69; 95%
      confidence interval, 0.68 to 0.69) and more likely to die in hospital (adjusted
      odds ratio, 1.27; 95% confidence interval, 1.25 to 1.29) for each 10-year age
      increase. CONCLUSIONS: Older patients with ischemic stroke differ in clinical
      characteristics and experience higher in-hospital mortality than younger
      patients. Performance measure-based treatment rates improved substantially over
      time for ischemic stroke patients in all age groups, resulting in smaller age
      related treatment gaps.

PMID- 20142444
TI  - Trends in incidence, severity, and outcome of hospitalized myocardial infarction.
AB  - BACKGROUND: In 2000, the definition of myocardial infarction (MI) changed to rely
      on troponin rather than creatine kinase (CK) and its MB fraction (CK-MB). The
      implications of this change on trends in MI incidence and outcome are not
      defined. METHODS AND RESULTS: This was a community study of 2816 patients
      hospitalized with incident MI from 1987 to 2006 in Olmsted County, Minnesota,
      with prospective measurements of troponin and CK-MB from August 2000 forward.
      Outcomes were MI incidence, severity, and survival. After troponin was
      introduced, 278 (25%) of 1127 incident MIs met only troponin-based criteria. When
      cases meeting only troponin criteria were included, incidence did not change
      between 1987 and 2006. When restricted to cases defined by CK/CK-MB, the
      incidence of MI declined by 20%. The incidence of non-ST-segment elevation MI
      increased markedly by relying on troponin, whereas that of ST-segment elevation
      MI declined regardless of troponin. The age- and sex-adjusted hazard ratio of
      death within 30 days for an infarction occurring in 2006 (compared with 1987) was
      0.44 (95% confidence interval, 0.30 to 0.64). Among 30-day survivors, survival
      did not improve, but causes of death shifted from cardiovascular to
      noncardiovascular (P=0.001). Trends in long-term survival among 30-day survivors
      were similar regardless of troponin. CONCLUSIONS: Over the last 2 decades, a
      substantial change in the epidemiology of MI occurred that was only partially
      mediated by the introduction of troponin. Non-ST-segment elevation MIs now
      constitute the majority of MIs. Although the 30-day case fatality improved
      markedly, long-term survival did not change, and the cause of death shifted from
      cardiovascular to noncardiovascular.

PMID- 20142446
TI  - Circulating endothelial progenitor cells do not contribute to plaque endothelium
      in murine atherosclerosis.
AB  - BACKGROUND: It has been reported that circulating endothelial progenitor cells
      (EPCs) home to and differentiate into endothelial cells after various kinds of
      arterial injury. By inference, EPCs are also proposed to be important in the most
      important arterial disease, atherosclerosis, but the evidence for this theory is
      not clear. In the present study, we assessed the contribution of circulating EPCs
      to plaque endothelium in apolipoprotein E-deficient (apoE(-/-)) mice. METHODS AND
      RESULTS: To investigate whether EPCs in the circulating blood are a source of
      plaque endothelial cells during atherogenesis, we examined plaques in lethally
      irradiated apoE(-/-) mice reconstituted with bone marrow cells from enhanced
      green fluorescent protein (eGFP) transgenic apoE(-/-) mice and plaques induced in
      segments of common carotid artery transplanted from apoE(-/-) mice into
      eGFP(+)apoE(-/-) mice. Among 4232 endothelial cells identified by a cell-type
      specific marker (von Willebrand factor) and analyzed by high-resolution
      microscopy, we found only 1 eGFP(+). Using the Y chromosome to track cells after
      sex-mismatched transplants yielded similar results. To investigate whether
      circulating EPCs are involved in plaque reendothelialization after plaque
      disruption and superimposed thrombosis, we produced mechanical plaque disruptions
      in carotid bifurcation plaques in old lethally irradiated apoE(-/-) mice
      reconstituted with eGFP(+)apoE(-/-) bone marrow cells and carotid bifurcation
      plaques transplanted from old apoE(-/-) mice into eGFP(+)apoE(-/-) mice. Only 1
      eGFP(+) endothelial cell was found among 3170 analyzed. CONCLUSIONS: Circulating
      EPCs rarely, if ever, contribute to plaque endothelium in apoE(-/-) mice. These
      findings bring into question the prevailing theory that circulating EPCs play an
      important role in atherogenesis.

PMID- 20142447
TI  - Predictors of outcomes in medically treated patients with acute coronary
      syndromes after angiographic triage: an Acute Catheterization And Urgent
      Intervention Triage Strategy (ACUITY) substudy.
AB  - BACKGROUND: Outcomes of patients presenting with acute coronary syndromes are
      improved with an early invasive approach; however, approximately one third of
      these patients are treated medically after angiographic screening. We sought to
      assess the predictors of adverse cardiac events in patients with acute coronary
      syndrome assigned to medical management. METHODS AND RESULTS: This substudy of
      the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial
      included 4491 acute coronary syndrome patients treated medically after
      angiographic triage. Rates of bleeding and composite ischemia (death, myocardial
      infarction, revascularization) were compared among the 3 antithrombotic treatment
      arms. Composite ischemia occurred in 399 patients (9.5%) at 1 year. Treatment
      with bivalirudin glycoprotein IIb/IIIa inhibitors significantly reduced major
      bleeding at 30 days (2.5% bivalirudin monotherapy; P=0.005, 2.0% bivalirudin plus
      glycoprotein IIb/IIIa inhibitors; P=0.0002 versus 4.4% heparin with glycoprotein
      IIb/IIIa inhibitors). Composite ischemic events at 1 year were not significantly
      different in the 3 groups (bivalirudin monotherapy, 9.6%; bivalirudin plus
      glycoprotein IIb/IIIa inhibitors, 9.7%; heparin plus glycoprotein IIb/IIIa
      inhibitors, 9.1%). Independent predictors of composite ischemia were mostly
      angiographic factors at 30 days, including jeopardy score and coronary ectasia,
      and at 1 year, including previous percutaneous coronary intervention, jeopardy
      score, coronary ectasia, and increasing number of diseased vessels. CONCLUSIONS:
      Among the ACUITY acute coronary syndrome patients treated medically after
      angiographic triage, bivalirudin therapy significantly reduced bleeding
      complications compared with heparin without any negative impact on ischemic
      outcomes at 1 year. The most powerful predictors of ischemic outcomes were
      angiographic rather than traditional clinical parameters, supporting the early
      use of angiographic screening in the moderate- and high-risk but medically
      treated acute coronary syndrome population. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

PMID- 20142448
TI  - Age-dependent profile of left-sided infective endocarditis: a 3-center
      experience.
AB  - BACKGROUND: The influence of age on the main epidemiological, clinical,
      echocardiographic, microbiological, and prognostic features of patients with
      infective endocarditis remains unknown. We present the series with the largest
      numbers and range of ages of subjects to date that analyzes the influence of age
      on the main characteristics of patients with isolated left-sided infective
      endocarditis. Furthermore, this series is the first one in which patients have
      been distributed according to age quartile. METHODS AND RESULTS: A total of 600
      episodes of left-sided endocarditis consecutively diagnosed in 3 tertiary centers
      were stratified into age-specific quartiles and 107 variables compared between
      the different groups. With increasing age, the percentage of women, previous
      heart disease, predisposing disease (diabetes mellitus and cancer), and infection
      by enterococci and Streptococcus bovis also increased. Valvular insufficiency and
      perforation and Staphylococcus aureus infection were more common in younger
      patients. The therapeutic approach differed depending on patient age because of
      the growing proportion of older patients who only received medical treatment.
      Clinical course and hospital prognosis were worse in the older patients because
      of increased surgical mortality among them. CONCLUSIONS: Increasing age is
      associated with less valvular impairment (insufficiency and perforation), a more
      favorable microbiological profile, and increased surgical mortality among adults
      with left-sided infective endocarditis.

PMID- 20142450
TI  - Getting the word out on stroke guidelines.

PMID- 20142449
TI  - Th17 and Th1 T-cell responses in giant cell arteritis.
AB  - BACKGROUND: In giant cell arteritis (GCA), vasculitic damage of the aorta and its
      branches is combined with a syndrome of intense systemic inflammation.
      Therapeutically, glucocorticoids remain the gold standard because they promptly
      and effectively suppress acute manifestations; however, they fail to eradicate
      vessel wall infiltrates. The effects of glucocorticoids on the systemic and
      vascular components of GCA are not understood. METHODS AND RESULTS: The
      immunoprofile of untreated and glucocorticoid-treated GCA was examined in
      peripheral blood and temporal artery biopsies with protein quantification assays,
      flow cytometry, quantitative real-time polymerase chain reaction, and
      immunohistochemistry. Plasma interferon-gamma and interleukin (IL)-17 and
      frequencies of interferon-gamma-producing and IL-17-producing T cells were
      markedly elevated before therapy. Glucocorticoid treatment suppressed the Th17
      but not the Th1 arm in the blood and the vascular lesions. Analysis of
      monocytes/macrophages in the circulation and in temporal arteries revealed
      glucocorticoid-mediated suppression of Th17-promoting cytokines (IL-1beta, IL-6,
      and IL-23) but sparing of Th1-promoting cytokines (IL-12). In human artery-severe
      combined immunodeficiency mouse chimeras, in which patient-derived T cells cause
      inflammation of engrafted human temporal arteries, glucocorticoids were similarly
      selective in inhibiting Th17 cells and leaving Th1 cells unaffected. CONCLUSIONS:
      Two pathogenic pathways mediated by Th17 and Th1 cells contribute to the systemic
      and vascular manifestations of GCA. IL-17-producing Th17 cells are sensitive to
      glucocorticoid-mediated suppression, but interferon-gamma-producing Th1 responses
      persist in treated patients. Targeting steroid-resistant Th1 responses will be
      necessary to resolve chronic smoldering vasculitis. Monitoring Th17 and Th1
      frequencies can aid in assessing disease activity in GCA.

PMID- 20142451
TI  - Ischemic cerebrovascular complications of cardiac procedures.

PMID- 20142452
TI  - Treating non-ST-segment elevation acute coronary syndromes: if you aren't sure,
      at least do no harm.

PMID- 20142453
TI  - Hard luck stories: the reality of endothelial progenitor cells continues to fall
      short of the promise.

PMID- 20142455
TI  - Genetic structure of an endemic Japanese conifer, Sciadopitys verticillata
      (Sciadopityaceae), by using microsatellite markers.
AB  - We investigated the genetic structure of Sciadopitys verticillata, an endemic
      conifer in Japan, using 11 microsatellite markers. Average expected
      heterozygosity varied from 0.282 to 0.450, with between 2 and 17 alleles per
      locus, and allelic richness varied from 2.14 to 2.94 within a population.
      Wilcoxon signed-rank tests suggested that there was a recent bottleneck in the
      southwestern populations in the Kinki district and in isolated northeastern
      populations in the Tohoku district. Bayesian clustering analysis showed that the
      populations of the Chubu, Kinki, and Shikoku districts were admixed from several
      clusters. Archaeological data suggest past anthropogenic exploitation for
      building and coffin material.

PMID- 20142454
TI  - Prevention of torsade de pointes in hospital settings: a scientific statement
      from the American Heart Association and the American College of Cardiology
      Foundation.

PMID- 20142456
TI  - Quantitative inheritance of crop timing traits in interspecific hybrid Petunia
      populations and interactions with crop quality parameters.
AB  - The leaf unfolding rate (i.e., development rate) and the number of nodes forming
      prior to floral initiation are 2 factors determining production times for
      floriculture crops. Wild relative species of the cultivated petunia (Petunia x
      hybrida Vilm.) that exhibited faster development rates than modern cultivars and
      may therefore be useful genetic sources to develop cultivars with decreased
      production time were identified. Three interspecific F(2) families, Petunia
      exserta Stehmann x P. axillaris (Lam.) Britton et al., P. x hybrida 'Mitchell' x
      P. axillaris, and P. axillaris x P. integrifolia (Hook.) Schinz & Thell. all
      exhibited transgressive segregation for development rate and node number below
      the first flower. Development rate and time to flower segregated independently in
      all families. Leaf number below the first flower was positively correlated with
      leaf unfolding rate in all families except P. axillaris x P. integrifolia. Time
      to flower was positively correlated with flower bud number in the P. x hybrida
      'Mitchell' x P. axillaris and P. axillaris x P. integrifolia families only. Based
      on these results, wild Petunia germplasm should be useful for developing petunia
      cultivars with reduced crop production times, but some negative effects on crop
      quality parameters may need to be overcome.

PMID- 20142457
TI  - Genetic diversity in the endangered tropical tree, Guaiacum sanctum
      (Zygophyllaceae).
AB  - Fragmentation of tropical forests has changed continuous tropical landscapes into
      a network of poorly connected fragments, reducing population sizes and
      potentially increasing genetic isolation. This study quantifies genetic diversity
      within and among the 7 extant populations of the endangered tropical tree
      Guaiacum sanctum in Costa Rica. We describe how genetic diversity differs between
      populations representing continuous and fragmented habitats. Allozyme analyses
      were conducted on adult samples from populations representing 2 geographic
      regions in northwestern Costa Rica. We found high levels of genetic diversity
      within the species (H(es) = 0.329) and significant but relatively small
      differences in allele frequencies among populations (G(ST) = 0.101) and between
      regions (G(ST) = 0.053). We found no differences in genetic diversity between
      fragmented and continuous populations. Evidence for significant isolation-by
      distance (IBD) was seen only when all populations were analyzed. If populations
      within the 2 regions were analyzed separately, IBD ceased to be significant. Our
      results suggest that the patterns of genetic diversity observed for G. sanctum
      may be caused by the ancient separation of populations into 2 disjunct geographic
      regions with extensive historical rates of gene flow among populations within
      each region. Recent forest fragmentation has not yet affected patterns of genetic
      diversity in this species.

PMID- 20142458
TI  - "The seagull cry": a sign of emergency after renal transplantation?

PMID- 20142459
TI  - Severe refractory hypoxemia 16 years after a gunshot injury: Multidetector CT
      angiography pattern and endovascular treatment.

PMID- 20142460
TI  - Letter by Barrios et al regarding article, "Influence of systolic and diastolic
      blood pressure on the risk of incident atrial fibrillation in women".

PMID- 20142462
TI  - Cardiovascular magnetic resonance.

PMID- 20142463
TI  - Cardiac involvement in sporadic inclusion-body myositis.

PMID- 20142464
TI  - A very rare neurocutaneous disorder in 2 siblings: Sjogren-Larsson syndrome.
AB  - Sjogren-Larsson syndrome is an autosomal-recessive hereditary disorder involving
      congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia.
      It is caused by the deficient activity of fatty aldehyde dehydrogenase. In this
      report, the authors describe 2 siblings with Sjogren-Larsson syndrome. Both the
      patients had generalized ichthyosis, and the older one had spastic paraplegia and
      mental retardation, and the fundus examination revealed foveal and parafoveal
      glistening dots. The authors report the large kinship with Sjogren-Larsson
      syndrome, which is a rare and most probably underdiagnosed syndrome.

PMID- 20142465
TI  - Outcomes in treatment of infantile spasms with pulse methylprednisolone.
AB  - The authors report their experience with intravenous methylprednisolone for the
      treatment of infantile spasms. A pulse dose of 20 mg/kg intravenous
      methylprednisolone on each of 3 successive days, followed by a 2-month oral
      prednisolone taper, led to the rapid remission (range, 2-6 days) of infantile
      spasms in 5 of 10 (50%) infants. In the subgroup of infants treated within 1
      month of onset, 5 of 6 (83%) experienced remission within 6 days. The authors
      estimate the medication cost of intravenous methylprednisolone with prednisolone
      taper to be less than $200. In comparison, the cost of a typical course of
      adrenocorticotropic hormone in the United States can exceed $70,000. Initial
      treatment with intravenous methylprednisolone and/or oral corticosteroids is a
      reasonable cost-effective approach to infantile spasms. The lack of serious side
      effects, low cost, availability, ease of administration, and comparable efficacy
      suggests that intravenous methylprednisolone merits consideration for study in
      randomized prospective trials.

PMID- 20142466
TI  - Acquired microcephaly, regression of milestones, mitochondrial dysfunction, and
      episodic rigidity in a 46,XY male with a de novo MECP2 gene mutation.
AB  - We report a case of acquired microcephaly in a male infant. Testing for mutations
      in the MECP2 gene identified a de novo hemizygous c.378-3C>G mutation at a highly
      conserved 3' splice site, consistent with Rett syndrome. Other distinctive
      features included periodic hypertonicity, decreased mitochondrial complex III
      activity, and abnormal magnetic resonance imaging (MRI) T2 signal in the pons.
      Rett syndrome was originally described in females with a clinical phenotype of
      deceleration of head growth, abnormal hand movements, and developmental
      regression. The clinical diagnosis can now be supported by genetic testing for
      MECP2 mutations, and the phenotype of disorder has expanded. Cases of Rett
      syndrome in males are rare and a total of 17 such cases have been reported. This
      case extends the clinical phenotype of Rett syndrome in males and associates this
      mutation with mitochondrial dysfunction.

PMID- 20142468
TI  - Corpus callosum morphology and its relationship to cognitive function in
      neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is associated with cognitive dysfunction and
      structural brain abnormalities such as an enlarged corpus callosum. This study
      aimed to determine the relationship between corpus callosum morphology and
      cognitive function in children with neurofibromatosis type 1 using quantitative
      neuroanatomic imaging techniques. Children with neurofibromatosis type 1 (n = 46)
      demonstrated a significantly larger total corpus callosum and corpus callosum
      index compared with control participants (n = 30). A larger corpus callosum index
      in children with neurofibromatosis type 1 was associated with significantly lower
      IQ, reduced abstract concept formation, reduced verbal memory, and diminished
      academic ability, specifically reading and math. Our results suggest an enlarged
      corpus callosum in children with neurofibromatosis type 1 is associated with
      cognitive impairment and may provide an early structural marker for the children
      at risk of cognitive difficulties. Cognitive deficits associated with structural
      brain abnormalities in neurofibromatosis type 1 are unlikely to be reversible and
      so may not respond to proposed pharmacological therapies for neurofibromatosis
      type 1-related cognitive impairments.

PMID- 20142469
TI  - To dip or not to dip: reconciling optical imaging and fMRI data.

PMID- 20142470
TI  - Human strategy updating in evolutionary games.
AB  - Evolutionary game dynamics describe not only frequency-dependent genetic
      evolution, but also cultural evolution in humans. In this context, successful
      strategies spread by imitation. It has been shown that the details of strategy
      update rules can have a crucial impact on evolutionary dynamics in theoretical
      models and, for example, can significantly alter the level of cooperation in
      social dilemmas. What kind of strategy update rules can describe imitation
      dynamics in humans? Here, we present a way to measure such strategy update rules
      in a behavioral experiment. We use a setting in which individuals are virtually
      arranged on a spatial lattice. This produces a large number of different
      strategic situations from which we can assess strategy updating. Most
      importantly, spontaneous strategy changes corresponding to mutations or
      exploration behavior are more frequent than assumed in many models. Our
      experimental approach to measure properties of the update mechanisms used in
      theoretical models will be useful for mathematical models of cultural evolution.

PMID- 20142471
TI  - Uridylation of mature miRNAs and siRNAs by the MUT68 nucleotidyltransferase
      promotes their degradation in Chlamydomonas.
AB  - Regulation of gene expression by small RNAs ( approximately 20-30 nucleotides in
      length) plays an essential role in developmental pathways and defense responses
      against genomic parasites in eukaryotes. MicroRNAs (miRNAs) and small interfering
      RNAs (siRNAs) commonly direct the inactivation of cognate sequences through a
      variety of mechanisms, including RNA degradation, translation inhibition, and
      transcriptional repression. Recent studies have provided considerable insight
      into the biogenesis and the mode of action of miRNAs and siRNAs. However,
      relatively little is known about mechanisms of quality control and small RNA
      decay in RNA interference (RNAi) pathways. Here we show that deletion of MUT68,
      encoding a terminal nucleotidyltransferase in the alga Chlamydomonas reinhardtii,
      results in elevated miRNA and siRNA levels. We found that MUT68 plays a role in
      the untemplated uridylation of the 3' ends of small RNAs in vivo and stimulates
      their degradation by the RRP6 exosome subunit in vitro. Moreover, RRP6 depletion
      also leads to accumulation of small RNAs in vivo. We propose that MUT68 and RRP6
      cooperate in the degradation of mature miRNAs and siRNAs, as a quality control
      mechanism to eliminate dysfunctional or damaged small RNA molecules.

PMID- 20142472
TI  - A developmental framework for endodermal differentiation and polarity.
AB  - The endodermis is a root cell layer common to higher plants and of fundamental
      importance for root function and nutrient uptake. The endodermis separates outer
      (peripheral) from inner (central) cell layers by virtue of its Casparian strips,
      precisely aligned bands of specialized wall material. Here we reveal that the
      membrane at the Casparian strip is a diffusional barrier between the central and
      peripheral regions of the plasma membrane and that it mediates attachment to the
      extracellular matrix. This membrane region thus functions like a tight junction
      in animal epithelia, although plants lack the molecular modules that establish
      tight junction in animals. We have also identified a pair of influx and efflux
      transporters that mark both central and peripheral domains of the plasma
      membrane. These transporters show opposite polar distributions already in
      meristems, but their localization becomes refined and restricted upon
      differentiation. This "central-peripheral" polarity coexists with the apical
      basal polarity defined by PIN proteins within the same cells, but utilizes
      different polarity determinants. Central-peripheral polarity can be already
      observed in early embryogenesis, where it reveals a cellular polarity within the
      quiescent center precursor cell. A strict diffusion block between polar domains
      is common in animals, but had never been described in plants. Yet, its relevance
      to endodermal function is evident, as central and peripheral membranes of the
      endodermis face fundamentally different root compartments. Further analysis of
      endodermal transporter polarity and manipulation of its barrier function will
      greatly promote our understanding of plant nutrition and stress tolerance in
      roots.

PMID- 20142473
TI  - Multilocus tetrasomic linkage analysis using hidden Markov chain model.
AB  - The availability of reliable genetic linkage maps is crucial for functional and
      evolutionary genomic analyses. Established theory and methods of genetic linkage
      analysis have made map construction a routine exercise in diploids. However, many
      evolutionarily, ecologically, and/or agronomically important species are
      autopolyploids, with autotetraploidy being a typical example. These species
      undergo much more complicated chromosomal segregation and recombination at
      meiosis than diploids. In addition, there is evidence of polyploidy-induced and
      highly dynamic changes in the structure of the genome. These polysomic
      characteristics indicate the inappropriateness of the theory and methods of
      linkage analysis in diploids for use in these species and a gap in the theory and
      methodology of tetraploid map construction. This paper presents a theoretical
      model and statistical framework for multilocus linkage analysis in
      autotetraploids for use with dominant and/or codominant DNA molecular markers.
      The theory and methods incorporate the essential features of allele segregation
      and recombination under tetrasomic inheritance and the major challenges in
      statistical modeling and marker data analysis. We validated the method and
      explored its statistical properties by intensive simulation study and
      demonstrated its utility by analysis of AFLP and SSR marker data from an outbred
      autotetraploid potato population.

PMID- 20142474
TI  - Centromere-localized breaks indicate the generation of DNA damage by the mitotic
      spindle.
AB  - Most carcinomas present some form of chromosome instability in combination with
      spindle defects. Numerical instability is likely caused by spindle aberrations,
      but the origin of breaks and translocations remains elusive. To determine whether
      one mechanism can bring about both types of instability, we studied the
      relationship between DNA damage and spindle defects. Although lacking apparent
      repair defects, primary Dido mutant cells formed micronuclei containing damaged
      DNA. The presence of centromeres showed that micronuclei were caused by spindle
      defects, and cell cycle markers showed that DNA damage was generated during
      mitosis. Although the micronuclei themselves persisted, the DNA damage within was
      repaired during S and G2 phases. DNA breaks in Dido mutant cells regularly
      colocalized with centromeres, which were occasionally distorted. Comparable
      defects were found in APC mutant cell lines, an independent system for spindle
      defects. On the basis of these results, we propose a model for break formation in
      which spindle defects lead to centromere shearing.

PMID- 20142475
TI  - Regulation of PI3-kinase/Akt signaling by muscle-enriched microRNA-486.
AB  - microRNAs (miRNAs) play key roles in modulating a variety of cellular processes
      through repression of mRNA targets. In a screen for miRNAs regulated by myocardin
      related transcription factor-A (MRTF-A), a coactivator of serum response factor
      (SRF), we discovered a muscle-enriched miRNA, miR-486, controlled by an
      alternative promoter within intron 40 of the Ankyrin-1 gene. Transcription of miR
      486 is directly controlled by SRF and MRTF-A, as well as by MyoD. Among the most
      strongly predicted targets of miR-486 are phosphatase and tensin homolog (PTEN)
      and Foxo1a, which negatively affect phosphoinositide-3-kinase (PI3K)/Akt
      signaling. Accordingly, PTEN and Foxo1a protein levels are reduced by miR-486
      overexpression, which, in turn, enhances PI3K/Akt signaling. Similarly, we show
      that MRTF-A promotes PI3K/Akt signaling by up-regulating miR-486 expression.
      Conversely, inhibition of miR-486 expression enhances the expression of PTEN and
      Foxo1a and dampens signaling through the PI3K/Akt-signaling pathway. Our findings
      implicate miR-486 as a downstream mediator of the actions of SRF/MRTF-A and MyoD
      in muscle cells and as a potential modulator of PI3K/Akt signaling.

PMID- 20142476
TI  - Cross-species analysis traces adaptation of Rubisco toward optimality in a low
      dimensional landscape.
AB  - Rubisco (D-ribulose 1,5-bisphosphate carboxylase/oxygenase), probably the most
      abundant protein in the biosphere, performs an essential part in the process of
      carbon fixation through photosynthesis, thus facilitating life on earth. Despite
      the significant effect that Rubisco has on the fitness of plants and other
      photosynthetic organisms, this enzyme is known to have a low catalytic rate and a
      tendency to confuse its substrate, carbon dioxide, with oxygen. This apparent
      inefficiency is puzzling and raises questions regarding the roles of evolution
      versus biochemical constraints in shaping Rubisco. Here we examine these
      questions by analyzing the measured kinetic parameters of Rubisco from various
      organisms living in various environments. The analysis presented here suggests
      that the evolution of Rubisco is confined to an effectively one-dimensional
      landscape, which is manifested in simple power law correlations between its
      kinetic parameters. Within this one-dimensional landscape, which may represent
      biochemical and structural constraints, Rubisco appears to be tuned to the
      intracellular environment in which it resides such that the net photosynthesis
      rate is nearly optimal. Our analysis indicates that the specificity of Rubisco is
      not the main determinant of its efficiency but rather the trade-off between the
      carboxylation velocity and CO(2) affinity. As a result, the presence of oxygen
      has only a moderate effect on the optimal performance of Rubisco, which is
      determined mostly by the local CO(2) concentration. Rubisco appears as an
      experimentally testable example for the evolution of proteins subject both to
      strong selection pressure and to biochemical constraints that strongly confine
      the evolutionary plasticity to a low-dimensional landscape.

PMID- 20142477
TI  - The early autophagic pathway is activated by hepatitis B virus and required for
      viral DNA replication.
AB  - Autophagy is a catabolic process by which cells remove long-lived proteins and
      damaged organelles for recycling. Viral infections may also induce autophagic
      response. Here we show that hepatitis B virus (HBV), a pathogen that chronically
      infects approximately 350 million people globally, can enhance autophagic
      response in cell cultures, mouse liver, and during natural infection. This
      enhancement of the autophagic response is not coupled by an increase of
      autophagic protein degradation and is dependent on the viral X protein, which
      binds to and enhances the enzymatic activity of phosphatidylinositol 3-kinase
      class III, an enzyme critical for the initiation of autophagy. Further analysis
      indicates that autophagy enhances HBV DNA replication, with minimal involvement
      of late autophagic vacuoles in this process. Our studies thus demonstrate that a
      DNA virus can use autophagy to enhance its own replication and indicate the
      possibility of targeting the autophagic pathway for the treatment of HBV
      patients.

PMID- 20142478
TI  - Retroviral infection in vivo requires an immune escape virulence factor encrypted
      in the envelope protein of oncoretroviruses.
AB  - We previously delineated a highly conserved immunosuppressive (IS) domain within
      murine and primate retroviral envelope proteins (Envs). The envelope-mediated
      immunosuppression was manifested by the ability of the proteins, when expressed
      by allogeneic tumor cells normally rejected by engrafted mice, to allow these
      cells to escape, at least transiently, immune rejection. Using this approach, we
      identified key residues whose mutation specifically abolishes IS activity without
      affecting the "mechanical" fusogenic function of the entire envelope. Here, we
      genetically "switched off' the envelope-mediated immunosuppression of an
      infectious retrovirus, the Friend murine leukemia virus, while preserving mutant
      envelope infectivity both ex vivo and in vivo, thus allowing us to test the
      functional importance of envelope-mediated immunosuppression in retrovirus
      physiology. Remarkably, we show, in vivo, that the non-IS mutant virus displays
      the same propagation kinetics as its WT counterpart in irradiated
      immunocompromised mice but that it is rapidly and totally cleared from normal
      immunocompetent mice, which become fully protected against a challenge with the
      WT retrovirus. Using cell depletion strategies, we further establish that
      envelope-mediated immunosuppression enables the retrovirus to escape innate
      (natural killer cells) and adaptive (CD8 T cells) antiviral effectors. Finally,
      we show that inactivated mutant virions induce higher humoral and cellular
      responses than their WT counterparts. In conclusion, our work demonstrates the
      critical role of Env-induced immunosuppression for retrovirus propagation in vivo
      and identifies a unique definite target for antiretroviral therapies and vaccine
      strategies, also characterized in the human T-cell leukemia virus (HTLV) and
      xenotropic murine leukemia virus-related virus (XMRV) retroviruses, opening
      unprecedented prospects for the treatment of retroviral diseases.

PMID- 20142479
TI  - Amoeboid organism solves complex nutritional challenges.
AB  - A fundamental question in nutritional biology is how distributed systems maintain
      an optimal supply of multiple nutrients essential for life and reproduction. In
      the case of animals, the nutritional requirements of the cells within the body
      are coordinated by the brain in neural and chemical dialogue with sensory systems
      and peripheral organs. At the level of an insect society, the requirements for
      the entire colony are met by the foraging efforts of a minority of workers
      responding to cues emanating from the brood. Both examples involve components
      specialized to deal with nutrient supply and demand (brains and peripheral
      organs, foragers and brood). However, some of the most species-rich, largest, and
      ecologically significant heterotrophic organisms on earth, such as the vast
      mycelial networks of fungi, comprise distributed networks without specialized
      centers: How do these organisms coordinate the search for multiple nutrients? We
      address this question in the acellular slime mold Physarum polycephalum and show
      that this extraordinary organism can make complex nutritional decisions, despite
      lacking a coordination center and comprising only a single vast multinucleate
      cell. We show that a single slime mold is able to grow to contact patches of
      different nutrient quality in the precise proportions necessary to compose an
      optimal diet. That such organisms have the capacity to maintain the balance of
      carbon- and nitrogen-based nutrients by selective foraging has considerable
      implications not only for our understanding of nutrient balancing in distributed
      systems but for the functional ecology of soils, nutrient cycling, and carbon
      sequestration.

PMID- 20142480
TI  - Phylogenetic analyses reveal the shady history of C4 grasses.
AB  - Grasslands cover more than 20% of the Earth's terrestrial surface, and their rise
      to dominance is one of the most dramatic events of biome evolution in Earth
      history. Grasses possess two main photosynthetic pathways: the C(3) pathway that
      is typical of most plants and a specialized C(4) pathway that minimizes
      photorespiration and thus increases photosynthetic performance in high
      temperature and/or low-CO(2) environments. C(4) grasses dominate tropical and
      subtropical grasslands and savannas, and C(3) grasses dominate the world's cooler
      temperate grassland regions. This striking pattern has been attributed to C(4)
      physiology, with the implication that the evolution of the pathway enabled C(4)
      grasses to persist in warmer climates than their C(3) relatives. We combined
      geospatial and molecular sequence data from two public archives to produce a
      1,230-taxon phylogeny of the grasses with accompanying climate data for all
      species, extracted from more than 1.1 million herbarium specimens. Here we show
      that grasses are ancestrally a warm-adapted clade and that C(4) evolution was not
      correlated with shifts between temperate and tropical biomes. Instead, 18 of 20
      inferred C(4) origins were correlated with marked reductions in mean annual
      precipitation. These changes are consistent with a shift out of tropical forest
      environments and into tropical woodland/savanna systems. We conclude that C(4)
      evolution in grasses coincided largely with migration out of the understory and
      into open-canopy environments. Furthermore, we argue that the evolution of cold
      tolerance in certain C(3) lineages is an overlooked innovation that has
      profoundly influenced the patterning of grassland communities across the globe.

PMID- 20142481
TI  - The Lucretian swerve: the biological basis of human behavior and the criminal
      justice system.
AB  - It is widely believed, at least in scientific circles, that living systems,
      including mankind, obey the natural physical laws. However, it is also commonly
      accepted that man has the capacity to make "free" conscious decisions that do not
      simply reflect the chemical makeup of the individual at the time of decision-
      this chemical makeup reflecting both the genetic and environmental history and a
      degree of stochasticism. Whereas philosophers have discussed for centuries the
      apparent lack of a causal component for free will, many biologists still seem to
      be remarkably at ease with this notion of free will; and furthermore, our
      judicial system is based on such a belief. It is the author's contention that a
      belief in free will is nothing other than a continuing belief in vitalism-
      something biologists proudly believe they discarded well over 100 years ago.

PMID- 20142482
TI  - Genetic approach for intracerebroventricular delivery.
AB  - Administration of synthetic or purified peptides directly into the brain
      ventricles is a method commonly used by neuroscientists for exploring
      physiological and behavioral functions of gene products. i.v. administration is
      controlled by the blood-brain barrier, which limits its effectiveness, and
      current approaches for acute or chronic intracerebroventricular delivery have
      significant technical drawbacks resulting from both the chemical properties of
      the delivered substance and the experimental procedures. Here we describe a
      genetic approach for the delivery of secreted peptides or proteins into the
      cerebrospinal fluid (CSF). Using a choroid plexus-specific promoter, we
      established a lentiviral-based system, which offers inducible and reversible
      delivery of a gene product into the CSF. The functionality of this system was
      demonstrated by using the overexpression of the two established neuropeptides,
      corticotropin-releasing factor and gonadotropin-releasing hormone, modulating
      anxiety-like behavior and estrus cycle, respectively. We show that this choroid
      plexus-specific lentiviral-based system is a reliable, effective, and adaptable
      research tool for intracerebroventricular delivery.

PMID- 20142483
TI  - Molecular MRI for sensitive and specific detection of lung metastases.
AB  - Early and specific detection of metastatic cancer cells in the lung (the most
      common organ targeted by metastases) could significantly improve cancer treatment
      outcomes. However, the most widespread lung imaging methods use ionizing
      radiation and have low sensitivity and/or low specificity for cancer cells. Here
      we address this problem with an imaging method to detect submillimeter-sized
      metastases with molecular specificity. Cancer cells are targeted by iron oxide
      nanoparticles functionalized with cancer-binding ligands, then imaged by high
      resolution hyperpolarized (3)He MRI. We demonstrate in vivo detection of
      pulmonary micrometastates in mice injected with breast adenocarcinoma cells. The
      method not only holds promise for cancer imaging but more generally suggests a
      fundamentally unique approach to molecular imaging in the lungs.

PMID- 20142484
TI  - Abasic sites and strand breaks in DNA cause transcriptional mutagenesis in
      Escherichia coli.
AB  - DNA damage occurs continuously, and faithful replication and transcription are
      essential for maintaining cell viability. Cells in nature are not dividing and
      replicating DNA often; therefore it is important to consider the outcome of RNA
      polymerase (RNAP) encounters with DNA damage. Base damage in the DNA can affect
      transcriptional fidelity, leading to production of mutant mRNA and protein in a
      process termed transcriptional mutagenesis (TM). Abasic (AP) sites and strand
      breaks are frequently occurring, spontaneous damages that are also base excision
      repair (BER) intermediates. In vitro studies have demonstrated that these lesions
      can be bypassed by RNAP; however this has never been assessed in vivo. This study
      demonstrates that RNAP is capable of bypassing AP sites and strand breaks in
      Escherichia coli and results in TM through adenine incorporation in nascent mRNA.
      Elimination of the enzymes that process these lesions further increases TM;
      however, such mutants can still complete repair by other downstream pathways.
      These results show that AP sites and strand breaks can result in mutagenic RNAP
      bypass and have important implications for the biologic endpoints of DNA damage.

PMID- 20142485
TI  - Molecular complexity of successive bacterial epidemics deconvoluted by
      comparative pathogenomics.
AB  - Understanding the fine-structure molecular architecture of bacterial epidemics
      has been a long-sought goal of infectious disease research. We used short-read
      length DNA sequencing coupled with mass spectroscopy analysis of SNPs to study
      the molecular pathogenomics of three successive epidemics of invasive infections
      involving 344 serotype M3 group A Streptococcus in Ontario, Canada. Sequencing
      the genome of 95 strains from the three epidemics, coupled with analysis of 280
      biallelic SNPs in all 344 strains, revealed an unexpectedly complex population
      structure composed of a dynamic mixture of distinct clonally related complexes.
      We discovered that each epidemic is dominated by micro- and macrobursts of
      multiple emergent clones, some with distinct strain genotype-patient phenotype
      relationships. On average, strains were differentiated from one another by only
      49 SNPs and 11 insertion-deletion events (indels) in the core genome. Ten percent
      of SNPs are strain specific; that is, each strain has a unique genome sequence.
      We identified nonrandom temporal-spatial patterns of strain distribution within
      and between the epidemic peaks. The extensive full-genome data permitted us to
      identify genes with significantly increased rates of nonsynonymous (amino acid
      altering) nucleotide polymorphisms, thereby providing clues about selective
      forces operative in the host. Comparative expression microarray analysis revealed
      that closely related strains differentiated by seemingly modest genetic changes
      can have significantly divergent transcriptomes. We conclude that enhanced
      understanding of bacterial epidemics requires a deep-sequencing, geographically
      centric, comparative pathogenomics strategy.

PMID- 20142486
TI  - Induction and patterning of trunk and tail neural ectoderm by the homeobox gene
      eve1 in zebrafish embryos.
AB  - In vertebrates, Evx homeodomain transcription factor-encoding genes are expressed
      in the posterior region during embryonic development, and overexpression
      experiments have revealed roles in tail development in fish and frogs. We
      analyzed the molecular mechanisms of posterior neural development and axis
      formation regulated by eve1. We show that eve1 is involved in establishing trunk
      and tail neural ectoderm by two independent mechanisms: First, eve1 posteriorizes
      neural ectoderm via induction of aldh1a2, which encodes an enzyme that
      synthesizes retinoic acid; second, eve1 is involved in neural induction in the
      posterior ectoderm by attenuating BMP expression. Further, eve1 can restore trunk
      neural tube formation in the organizer-deficient ichabod(-/-) mutant. We conclude
      that eve1 is crucial for the organization of the antero-posterior and dorso
      ventral axis in the gastrula ectoderm and also has trunk- and tail-promoting
      activity.

PMID- 20142487
TI  - Small-molecule screen identifies reactive oxygen species as key regulators of
      neutrophil chemotaxis.
AB  - Neutrophil chemotaxis plays an essential role in innate immunity, but the
      underlying cellular mechanism is still not fully characterized. Here, using a
      small-molecule functional screening, we identified NADPH oxidase-dependent
      reactive oxygen species as key regulators of neutrophil chemotactic migration.
      Neutrophils with pharmacologically inhibited oxidase, or isolated from chronic
      granulomatous disease (CGD) patients and mice, formed more frequent multiple
      pseudopodia and lost their directionality as they migrated up a chemoattractant
      concentration gradient. Knocking down NADPH oxidase in differentiated neutrophil
      like HL60 cells also led to defective chemotaxis. Consistent with the in vitro
      results, adoptively transferred CGD murine neutrophils showed impaired in vivo
      recruitment to sites of inflammation. Together, these results present a
      physiological role for reactive oxygen species in regulating neutrophil functions
      and shed light on the pathogenesis of CGD.

PMID- 20142488
TI  - BDNF variant Val66Met interacts with estrous cycle in the control of hippocampal
      function.
AB  - Natural fluctuations in circulating estradiol are associated with behavioral
      changes, including severe disturbances in mood and cognition in some women.
      Common genetic variation in some of the molecular mediators of estradiol effects
      on these behaviors, in brain regions such as the hippocampus, may explain
      individual variation in estradiol effects on behavior. We tested whether the
      common human variant BDNF Val66Met interacts with estradiol in the control of
      hippocampal function in cycling female mice homozygous for the wild-type Val or
      BDNF Met variant. BDNF Met increased anxiety behavior, impaired memory, and
      increased expression of BDNF and its receptor TrkB in the hippocampal formation.
      BDNF Met also dramatically altered the fluctuation of spatial memory, hippocampal
      Akt phosphorylation, and PSD-95 protein expression across the estrous cycle. The
      variant BDNF Val66Met should therefore be considered as a strong candidate for
      mediating genetic differences in ovarian steroid-related behavioral changes and
      disorders.

PMID- 20142489
TI  - Membrane-anchored serine protease matriptase regulates epithelial barrier
      formation and permeability in the intestine.
AB  - The intestinal epithelium serves as a major protective barrier between the
      mammalian host and the external environment. Here we show that the transmembrane
      serine protease matriptase plays a pivotol role in the formation and integrity of
      the intestinal epithelial barrier. St14 hypomorphic mice, which have a 100-fold
      reduction in intestinal matriptase mRNA levels, display a 35% reduction in
      intestinal transepithelial electrical resistance (TEER). Matriptase is expressed
      during intestinal epithelial differentiation and colocalizes with E-cadherin to
      apical junctional complexes (AJC) in differentiated polarized Caco-2 monolayers.
      Inhibition of matriptase activity using a specific peptide inhibitor or by
      knockdown of matriptase by siRNA disrupts the development of TEER in barrier
      forming Caco-2 monolayers and increases paracellular permeability to
      macromolecular FITC-dextran. Loss of matriptase was associated with enhanced
      expression and incorporation of the permeability-associated, "leaky" tight
      junction protein claudin-2 at intercellular junctions. Knockdown of claudin-2
      enhanced the development of TEER in matriptase-silenced Caco-2 monolayers,
      suggesting that the reduced barrier integrity was caused, at least in part, by an
      inability to regulate claudin-2 expression and incorporation into junctions. We
      find that matriptase enhances the rate of claudin-2 protein turnover, and that
      this is mediated indirectly through an atypical PKCzeta-dependent signaling
      pathway. These results support a key role for matriptase in regulating intestinal
      epithelial barrier competence, and suggest an intriguing link between
      pericellular serine protease activity and tight junction assembly in polarized
      epithelia.

PMID- 20142490
TI  - Amygdala damage eliminates monetary loss aversion.
AB  - Losses are a possibility in many risky decisions, and organisms have evolved
      mechanisms to evaluate and avoid them. Laboratory and field evidence suggests
      that people often avoid risks with losses even when they might earn a
      substantially larger gain, a behavioral preference termed "loss aversion." The
      cautionary brake on behavior known to rely on the amygdala is a plausible
      candidate mechanism for loss aversion, yet evidence for this idea has so far not
      been found. We studied two rare individuals with focal bilateral amygdala lesions
      using a series of experimental economics tasks. To measure individual sensitivity
      to financial losses we asked participants to play a variety of monetary gambles
      with possible gains and losses. Although both participants retained a normal
      ability to respond to changes in the gambles' expected value and risk, they
      showed a dramatic reduction in loss aversion compared to matched controls. The
      findings suggest that the amygdala plays a key role in generating loss aversion
      by inhibiting actions with potentially deleterious outcomes.

PMID- 20142491
TI  - Functional cis-regulatory genomics for systems biology.
AB  - Gene expression is controlled by interactions between trans-regulatory factors
      and cis-regulatory DNA sequences, and these interactions constitute the essential
      functional linkages of gene regulatory networks (GRNs). Validation of GRN models
      requires experimental cis-regulatory tests of predicted linkages to authenticate
      their identities and proposed functions. However, cis-regulatory analysis is, at
      present, at a severe bottleneck in genomic system biology because of the
      demanding experimental methodologies currently in use for discovering cis
      regulatory modules (CRMs), in the genome, and for measuring their activities.
      Here we demonstrate a high-throughput approach to both discovery and quantitative
      characterization of CRMs. The unique aspect is use of DNA sequence tags to
      "barcode" CRM expression constructs, which can then be mixed, injected together
      into sea urchin eggs, and subsequently deconvolved. This method has increased the
      rate of cis-regulatory analysis by >100-fold compared with conventional one-by
      one reporter assays. The utility of the DNA-tag reporters was demonstrated by the
      rapid discovery of 81 active CRMs from 37 previously unexplored sea urchin genes.
      We then obtained simultaneous high-resolution temporal characterization of the
      regulatory activities of more than 80 CRMs. On average 2-3 CRMs were discovered
      per gene. Comparison of endogenous gene expression profiles with those of the
      CRMs recovered from each gene showed that, for most cases, at least one CRM is
      active in each phase of endogenous expression, suggesting that CRM recovery was
      comprehensive. This approach will qualitatively alter the practice of GRN
      construction as well as validation, and will impact many additional areas of
      regulatory system biology.

PMID- 20142492
TI  - Indirect land-use changes can overcome carbon savings from biofuels in Brazil.
AB  - The planned expansion of biofuel plantations in Brazil could potentially cause
      both direct and indirect land-use changes (e.g., biofuel plantations replace
      rangelands, which replace forests). In this study, we use a spatially explicit
      model to project land-use changes caused by that expansion in 2020, assuming that
      ethanol (biodiesel) production increases by 35 (4) x 10(9) liter in the 2003-2020
      period. Our simulations show that direct land-use changes will have a small
      impact on carbon emissions because most biofuel plantations would replace
      rangeland areas. However, indirect land-use changes, especially those pushing the
      rangeland frontier into the Amazonian forests, could offset the carbon savings
      from biofuels. Sugarcane ethanol and soybean biodiesel each contribute to nearly
      half of the projected indirect deforestation of 121,970 km(2) by 2020, creating a
      carbon debt that would take about 250 years to be repaid using these biofuels
      instead of fossil fuels. We also tested different crops that could serve as
      feedstock to fulfill Brazil's biodiesel demand and found that oil palm would
      cause the least land-use changes and associated carbon debt. The modeled
      livestock density increases by 0.09 head per hectare. But a higher increase of
      0.13 head per hectare in the average livestock density throughout the country
      could avoid the indirect land-use changes caused by biofuels (even with soybean
      as the biodiesel feedstock), while still fulfilling all food and bioenergy
      demands. We suggest that a closer collaboration or strengthened institutional
      link between the biofuel and cattle-ranching sectors in the coming years is
      crucial for effective carbon savings from biofuels in Brazil.

PMID- 20142493
TI  - Thalamic deactivation at sleep onset precedes that of the cerebral cortex in
      humans.
AB  - Thalamic and cortical activities are assumed to be time-locked throughout all
      vigilance states. Using simultaneous intracortical and intrathalamic recordings,
      we demonstrate here that the thalamic deactivation occurring at sleep onset most
      often precedes that of the cortex by several minutes, whereas reactivation of
      both structures during awakening is synchronized. Delays between thalamus and
      cortex deactivations can vary from one subject to another when a similar cortical
      region is considered. In addition, heterogeneity in activity levels throughout
      the cortical mantle is larger than previously thought during the descent into
      sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep
      probably explains the production of hypnagogic hallucinations by a still
      activated cortex and the common self-overestimation of the time needed to fall
      asleep.

PMID- 20142494
TI  - A cell protection screen reveals potent inhibitors of multiple stages of the
      hepatitis C virus life cycle.
AB  - The hepatitis C virus (HCV) life cycle involves multiple steps, but most current
      drug candidates target only viral replication. The inability to systematically
      discover inhibitors targeting multiple steps of the HCV life cycle has hampered
      antiviral development. We present a simple screen for HCV antivirals based on the
      alleviation of HCV-mediated cytopathic effect in an engineered cell line-n4mBid.
      This approach obviates the need for a secondary screen to avoid cytotoxic false
      positive hits. Application of our screen to 1280 compounds, many in clinical
      trials or approved for therapeutic use, yielded >200 hits. Of the 55 leading
      hits, 47 inhibited one or more aspects of the HCV life cycle by >40%. Six
      compounds blocked HCV entry to levels similar to an antibody (JS-81) targeting
      the HCV entry receptor CD81. Seven hits inhibited HCV replication and/or
      infectious virus production by >100-fold, with one (quinidine) inhibiting
      infectious virus production by 450-fold relative to HCV replication levels. This
      approach is simple and inexpensive and should enable the rapid discovery of new
      classes of HCV life cycle inhibitors.

PMID- 20142495
TI  - Redox potential of pheophytin a in photosystem II of two cyanobacteria having the
      different special pair chlorophylls.
AB  - Water oxidation by photosystem (PS) II in oxygenic photosynthetic organisms is a
      major source of energy on the earth, leading to the production of a stable
      reductant. Mechanisms generating a high oxidation potential for water oxidation
      have been a major focus of photosynthesis research. This potential has not been
      estimated directly but has been measured by the redox potential of the primary
      electron acceptor, pheophytin (Phe) a. However, the reported values for Phe a are
      still controversial. Here, we measured the redox potential of Phe a under
      physiological conditions (pH 7.0; 25 degrees C) in two cyanobacteria with
      different special pair chlorophylls (Chls): Synechocystis sp. PCC 6803, whose
      special pair for PS II consists of Chl a, and Acaryochloris marina MBIC 11017,
      whose special pair for PS II consists of Chl d. We obtained redox potentials of 
      536 +/- 8 mV for Synechocystis sp. PCC 6803 and -478 +/- 24 mV for A. marina on
      PS II complexes in the presence of 1.0 M betaine. The difference in the redox
      potential of Phe a between the two species closely corresponded with the
      difference in the light energy absorbed by Chl a versus Chl d. We estimated the
      potentials of the special pair of PS II to be 1.20 V and 1.18 V for Synechocystis
      sp. PCC 6803 (P680) and A. marina (P713), respectively. This clearly indicates
      conservation in the properties of water-oxidation systems in oxygenic
      photosynthetic organisms, irrespective of the special-pair chlorophylls.

PMID- 20142496
TI  - Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved
      stem cell regulator.
AB  - Stem cells are essential for tissue generation during the development of
      multicellular creatures, and for tissue homeostasis in adults. The great
      therapeutic promise of stem cells makes understanding their regulation a high
      priority. PUF RNA-binding proteins have a conserved role in promoting self
      renewal of germline stem cells. Here we use a genome-wide approach to identify
      putative target mRNAs for the Caenorhabditis elegans PUF protein known as FBF. We
      find that putative FBF targets represent approximately 7% of all protein-coding
      genes in C. elegans, implicating FBF as a broad-spectrum gene regulator. These
      putative FBF targets are enriched for regulators of meiotic entry and other
      components of the meiotic program as well as regulators of key developmental
      pathways. We suggest that these targets may be critical for FBF's role in stem
      cell maintenance. Comparison of likely FBF target mRNAs with putative PUF target
      mRNAs from Drosophila and humans reveals 40 shared targets, including several
      established stem cell regulators. We speculate that shared PUF targets represent
      part of a broadly used module of stem cell control.

PMID- 20142497
TI  - Nitrate-responsive miR393/AFB3 regulatory module controls root system
      architecture in Arabidopsis thaliana.
AB  - One of the most striking examples of plant developmental plasticity to changing
      environmental conditions is the modulation of root system architecture (RSA) in
      response to nitrate supply. Despite the fundamental and applied significance of
      understanding this process, the molecular mechanisms behind nitrate-regulated
      changes in developmental programs are still largely unknown. Small RNAs (sRNAs)
      have emerged as master regulators of gene expression in plants and other
      organisms. To evaluate the role of sRNAs in the nitrate response, we sequenced
      sRNAs from control and nitrate-treated Arabidopsis seedlings using the 454
      sequencing technology. miR393 was induced by nitrate in these experiments. miR393
      targets transcripts that code for a basic helix-loop-helix (bHLH) transcription
      factor and for the auxin receptors TIR1, AFB1, AFB2, and AFB3. However, only AFB3
      was regulated by nitrate in roots under our experimental conditions. Analysis of
      the expression of this miR393/AFB3 module, revealed an incoherent feed-forward
      mechanism that is induced by nitrate and repressed by N metabolites generated by
      nitrate reduction and assimilation. To understand the functional role of this N
      regulatory module for plant development, we analyzed the RSA response to nitrate
      in AFB3 insertional mutant plants and in miR393 overexpressors. RSA analysis in
      these plants revealed that both primary and lateral root growth responses to
      nitrate were altered. Interestingly, regulation of RSA by nitrate was
      specifically mediated by AFB3, indicating that miR393/AFB3 is a unique N
      responsive module that controls root system architecture in response to external
      and internal N availability in Arabidopsis.

PMID- 20142498
TI  - Mature dendritic cells use endocytic receptors to capture and present antigens.
AB  - In response to inflammatory stimuli, dendritic cells (DCs) trigger the process of
      maturation, a terminal differentiation program required to initiate T-lymphocyte
      responses. A hallmark of maturation is down-regulation of endocytosis, which is
      widely assumed to restrict the ability of mature DCs to capture and present
      antigens encountered after the initial stimulus. We found that mature DCs
      continue to accumulate antigens, especially by receptor-mediated endocytosis and
      phagocytosis. Internalized antigens are transported normally to late endosomes
      and lysosomes, loaded onto MHC class II molecules (MHCII), and then presented
      efficiently to T cells. This occurs despite the fact that maturation results in
      the general depletion of MHCII from late endocytic compartments, with MHCII
      enrichment being typically thought to be a required feature of antigen processing
      and peptide loading compartments. Internalized antigens can also be cross
      presented on MHC class I molecules, without any reduction in efficiency relative
      to immature DCs. Thus, although mature DCs markedly down-regulate their capacity
      for macropinocytosis, they continue to capture, process, and present antigens
      internalized via endocytic receptors, suggesting that they may continuously
      initiate responses to newly encountered antigens during the course of an
      infection.

PMID- 20142499
TI  - Loss of myeloid cell-derived vascular endothelial growth factor accelerates
      fibrosis.
AB  - Tissue injury initiates a complex series of events that act to restore structure
      and physiological homeostasis. Infiltration of inflammatory cells and vascular
      remodeling are both keystones of this process. However, the role of inflammation
      and angiogenesis in general and, more specifically, the significance of
      inflammatory cell-derived VEGF in this context are unclear. To determine the role
      of inflammatory cell-derived VEGF in a clinically relevant and chronically
      inflamed injury, pulmonary fibrosis, we deleted the VEGF-A gene in myeloid cells.
      In a model of pulmonary fibrosis in mice, deletion of VEGF in myeloid cells
      resulted in significantly reduced formation of blood vessels; however, it causes
      aggravated fibrotic tissue damage. This was accompanied by a pronounced decrease
      in epithelial cell survival and a striking increase in myofibroblast invasion.
      The drastic increase in fibrosis following loss of myeloid VEGF in the damaged
      lungs was also marked by increased levels of hypoxia-inducible factor (HIF)
      expression and Wnt/beta-catenin signaling. This demonstrates that the process of
      angiogenesis, driven by myeloid cell-derived VEGF, is essential for the
      prevention of fibrotic damage.

PMID- 20142500
TI  - Ultrahigh-throughput screening in drop-based microfluidics for directed
      evolution.
AB  - The explosive growth in our knowledge of genomes, proteomes, and metabolomes is
      driving ever-increasing fundamental understanding of the biochemistry of life,
      enabling qualitatively new studies of complex biological systems and their
      evolution. This knowledge also drives modern biotechnologies, such as molecular
      engineering and synthetic biology, which have enormous potential to address
      urgent problems, including developing potent new drugs and providing
      environmentally friendly energy. Many of these studies, however, are ultimately
      limited by their need for even-higher-throughput measurements of biochemical
      reactions. We present a general ultrahigh-throughput screening platform using
      drop-based microfluidics that overcomes these limitations and revolutionizes both
      the scale and speed of screening. We use aqueous drops dispersed in oil as
      picoliter-volume reaction vessels and screen them at rates of thousands per
      second. To demonstrate its power, we apply the system to directed evolution,
      identifying new mutants of the enzyme horseradish peroxidase exhibiting catalytic
      rates more than 10 times faster than their parent, which is already a very
      efficient enzyme. We exploit the ultrahigh throughput to use an initial purifying
      selection that removes inactive mutants; we identify approximately 100 variants
      comparable in activity to the parent from an initial population of approximately
      10(7). After a second generation of mutagenesis and high-stringency screening, we
      identify several significantly improved mutants, some approaching diffusion
      limited efficiency. In total, we screen approximately 10(8) individual enzyme
      reactions in only 10 h, using < 150 microL of total reagent volume; compared to
      state-of-the-art robotic screening systems, we perform the entire assay with a
      1,000-fold increase in speed and a 1-million-fold reduction in cost.

PMID- 20142501
TI  - Targeted metabolic labeling of yeast N-glycans with unnatural sugars.
AB  - Metabolic labeling of glycans with synthetic sugar analogs has emerged as an
      attractive means for introducing nonnatural chemical functionality into
      glycoproteins. However, the complexities of glycan biosynthesis prevent the
      installation of nonnatural moieties at defined, predictable locations within
      glycoproteins at high levels of incorporation. Here, we demonstrate that the
      conserved N-acetyglucosamine (GlcNAc) residues within chitobiose cores of N
      glycans in the model organism Saccharomyces cerevisiae can be specifically
      targeted for metabolic replacement by unnatural sugars. We introduced an
      exogenous GlcNAc salvage pathway into yeast, allowing cells to metabolize GlcNAc
      provided as a supplement to the culture medium. We then rendered the yeast
      auxotrophic for production of the donor nucleotide-sugar uridine-diphosphate
      GlcNAc (UDP-GlcNAc) by deletion of the essential gene GNA1. We demonstrate that
      gna1Delta strains require a GlcNAc supplement and that expression plasmids
      containing both exogenous components of the salvage pathway, GlcNAc transporter
      NGT1 from Candida albicans and GlcNAc kinase NAGK from Homo sapiens, are required
      for rescue in this context. Further, we show that cells successfully incorporate
      synthetic GlcNAc analogs N-azidoacetyglucosamine (GlcNAz) and N-(4-pentynoyl)
      glucosamine (GlcNAl) into cell-surface glycans and secreted glycoproteins. To
      verify incorporation of the nonnatural sugars at N-glycan core positions,
      endoglycosidase H (endoH)-digested peptides from a purified secretory
      glycoprotein, Ygp1, were analyzed by mass spectrometry. Multiple Ygp1 N
      glycosylation sites bearing GlcNAc, isotopically labeled GlcNAc, or GlcNAz were
      identified; these modifications were dependent on the supplement added to the
      culture medium. This system enables the production of glycoproteins that are
      functionalized for specific chemical modifications at their glycosylation sites.

PMID- 20142502
TI  - The structure of the harmonin/sans complex reveals an unexpected interaction mode
      of the two Usher syndrome proteins.
AB  - The hereditary hearing-vision loss disease, Usher syndrome I (USH1), is caused by
      defects in several proteins that can interact with each other in vitro. Defects
      in USH1 proteins are thought to be responsible for the developmental and
      functional impairments of sensory cells in the retina and inner ear.
      Harmonin/USH1C and Sans/USH1G are two of the USH1 proteins that interact with
      each other. Harmonin also binds to other USH1 proteins such as cadherin 23
      (CDH23) and protocadherin 15 (PCDH15). However, the molecular basis governing the
      harmonin and Sans interaction is largely unknown. Here, we report an unexpected
      assembly mode between harmonin and Sans. We demonstrate that the N-terminal
      domain and the first PDZ domain of harmonin are tethered by a small-domain C
      terminal to PDZ1 to form a structural and functional supramodule responsible for
      binding to Sans. We discover that the SAM domain of Sans, specifically, binds to
      the PDZ domain of harmonin, revealing previously unknown interaction modes for
      both PDZ and SAM domains. We further show that the synergistic PDZ1/SAM and
      PDZ1/carboxyl PDZ binding-motif interactions, between harmonin and Sans, lock the
      two scaffold proteins into a highly stable complex. Mutations in harmonin and
      Sans found in USH1 patients are shown to destabilize the complex formation of the
      two proteins.

PMID- 20142503
TI  - Histidine-mediated RNA transfer to GDP for unique mRNA capping by vesicular
      stomatitis virus RNA polymerase.
AB  - The RNA-dependent RNA polymerase L protein of vesicular stomatitis virus, a
      prototype of nonsegmented negative-strand (NNS) RNA viruses, forms a covalent
      complex with a 5'-phosphorylated viral mRNA-start sequence (L-pRNA), a putative
      intermediate in the unconventional mRNA capping reaction catalyzed by the RNA:GDP
      polyribonucleotidyltransferase (PRNTase) activity. Here, we directly demonstrate
      that the purified L-pRNA complex transfers pRNA to GDP to produce the capped RNA
      (Gpp-pRNA), indicating that the complex is a bona fide intermediate in the RNA
      transfer reaction. To locate the active site of the PRNTase domain in the L
      protein, the covalent RNA attachment site was mapped. We found that the 5'
      monophosphate end of the RNA is linked to the histidine residue at position 1,227
      (H1227) of the L protein through a phosphoamide bond. Interestingly, H1227 is
      part of the histidine-arginine (HR) motif, which is conserved within the L
      proteins of the NNS RNA viruses including rabies, measles, Ebola, and Borna
      disease viruses. Mutagenesis analyses revealed that the HR motif is required for
      the PRNTase activity at the step of the enzyme-pRNA intermediate formation. Thus,
      our findings suggest that an ancient NNS RNA viral polymerase has acquired the
      PRNTase domain independently of the eukaryotic mRNA capping enzyme during
      evolution and PRNTase becomes a rational target for designing antiviral agents.

PMID- 20142504
TI  - Formation of carcinogens indoors by surface-mediated reactions of nicotine with
      nitrous acid, leading to potential thirdhand smoke hazards.
AB  - This study shows that residual nicotine from tobacco smoke sorbed to indoor
      surfaces reacts with ambient nitrous acid (HONO) to form carcinogenic tobacco
      specific nitrosamines (TSNAs). Substantial levels of TSNAs were measured on
      surfaces inside a smoker's vehicle. Laboratory experiments using cellulose as a
      model indoor material yielded a > 10-fold increase of surface-bound TSNAs when
      sorbed secondhand smoke was exposed to 60 ppbv HONO for 3 hours. In both cases we
      identified 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal, a TSNA absent in
      freshly emitted tobacco smoke, as the major product. The potent carcinogens 4
      (methylnitrosamino)-1-(3-pyridinyl)-1-butanone and N-nitroso nornicotine were
      also detected. Time-course measurements revealed fast TSNA formation, with up to
      0.4% conversion of nicotine. Given the rapid sorption and persistence of high
      levels of nicotine on indoor surfaces-including clothing and human skin-this
      recently identified process represents an unappreciated health hazard through
      dermal exposure, dust inhalation, and ingestion. These findings raise concerns
      about exposures to the tobacco smoke residue that has been recently dubbed
      "thirdhand smoke." Our work highlights the importance of reactions at indoor
      interfaces, particularly those involving amines and NO(x)/HONO cycling, with
      potential health impacts.

PMID- 20142505
TI  - Mechanism of chromatin remodeling.
AB  - Results from biochemical and structural studies of the RSC chromatin-remodeling
      complex prompt a proposal for the remodeling mechanism: RSC binding to the
      nucleosome releases the DNA from the histone surface and initiates DNA
      translocation (through one or a small number of DNA base pairs); ATP binding
      completes translocation, and ATP hydrolysis resets the system. Binding energy
      thus plays a central role in the remodeling process. RSC may disrupt histone-DNA
      contacts by affecting histone octamer conformation and through extensive
      interaction with the DNA. Bulging of the DNA from the octamer surface is
      possible, and twisting is unavoidable, but neither is the basis of remodeling.

PMID- 20142506
TI  - Construction and genetic selection of small transmembrane proteins that activate
      the human erythropoietin receptor.
AB  - This work describes a genetic approach to isolate small, artificial transmembrane
      (TM) proteins with biological activity. The bovine papillomavirus E5 protein is a
      dimeric, 44-amino acid TM protein that transforms cells by specifically binding
      and activating the platelet-derived growth factor beta receptor (PDGFbetaR). We
      used the E5 protein as a scaffold to construct a retrovirus library expressing
      approximately 500,000 unique 44-amino acid proteins with randomized TM domains.
      We screened this library to select small, dimeric TM proteins that were
      structurally unrelated to erythropoietin (EPO), but specifically activated the
      human EPO receptor (hEPOR). These proteins did not activate the murine EPOR or
      the PDGFbetaR. Genetic studies with one of these activators suggested that it
      interacted with the TM domain of the hEPOR. Furthermore, this TM activator
      supported erythroid differentiation of primary human hematopoietic progenitor
      cells in vitro in the absence of EPO. Thus, we have changed the specificity of a
      protein so that it no longer recognizes its natural target but, instead,
      modulates an entirely different protein. This represents a novel strategy to
      isolate small artificial proteins that affect diverse membrane proteins. We
      suggest the word "traptamer" for these transmembrane aptamers.

PMID- 20142507
TI  - Stem cell-specific activation of an ancestral myc protooncogene with conserved
      basic functions in the early metazoan Hydra.
AB  - The c-myc protooncogene encodes a transcription factor (Myc) with oncogenic
      potential. Myc and its dimerization partner Max are bHLH-Zip DNA binding proteins
      controlling fundamental cellular processes. Deregulation of c-myc leads to
      tumorigenesis and is a hallmark of many human cancers. We have identified and
      extensively characterized ancestral forms of myc and max genes from the early
      diploblastic cnidarian Hydra, the most primitive metazoan organism employed so
      far for the structural, functional, and evolutionary analysis of these genes.
      Hydra myc is specifically activated in all stem cells and nematoblast nests which
      represent the rapidly proliferating cell types of the interstitial stem cell
      system and in proliferating gland cells. In terminally differentiated nerve
      cells, nematocytes, or epithelial cells, myc expression is not detectable by in
      situ hybridization. Hydra max exhibits a similar expression pattern in
      interstitial cell clusters. The ancestral Hydra Myc and Max proteins display the
      principal design of their vertebrate derivatives, with the highest degree of
      sequence identities confined to the bHLH-Zip domains. Furthermore, the 314-amino
      acid Hydra Myc protein contains basic forms of the essential Myc boxes I through
      III. A recombinant Hydra Myc/Max complex binds to the consensus DNA sequence
      CACGTG with high affinity. Hybrid proteins composed of segments from the
      retroviral v-Myc oncoprotein and the Hydra Myc protein display oncogenic
      potential in cell transformation assays. Our results suggest that the principal
      functions of the Myc master regulator arose very early in metazoan evolution,
      allowing their dissection in a simple model organism showing regenerative ability
      but no senescence.

PMID- 20142508
TI  - An expedient route to substituted furans via olefin cross-metathesis.
AB  - The olefin cross-metathesis (CM) reaction is used extensively in organic
      chemistry and represents a powerful method for the selective synthesis of
      differentially substituted alkene products. Surprisingly, efforts to integrate
      this remarkable process into strategies for aromatic and heteroaromatic
      construction have not been reported. Such structures represent key elements of
      the majority of small molecule drug compounds; methods for the controlled
      preparation of highly substituted derivatives are essential to medicinal
      chemistry. Here we show that the olefin CM reaction, in combination with an acid
      cocatalyst or subsequent Heck arylation, provides a concise and flexible entry to
      2,5-di- or 2,3,5-tri-substituted furans. These cascade processes portend further
      opportunities for the regiocontrolled preparation of other highly substituted
      aromatic and heteroaromatic classes.

PMID- 20142509
TI  - Repositioning of an existing drug for the neglected tropical disease
      Onchocerciasis.
AB  - Onchocerciasis, or river blindness, is a neglected tropical disease caused by the
      filarial nematode Onchocerca volvulus that affects more than 37 million people,
      mainly in third world countries. Currently, the only approved drug available for
      mass treatment is ivermectin, however, drug resistance is beginning to emerge,
      thus, new therapeutic targets and agents are desperately needed to treat and cure
      this devastating disease. Chitin metabolism plays a central role in invertebrate
      biology due to the critical structural function of chitin for the organism. Taken
      together with its absence in mammals, targeting chitin is an appealing
      therapeutic avenue. Importantly, the chitinase OvCHT1 from O. volvulus was
      recently discovered, however, its exact role in the worm's metabolism remains
      unknown. A screening effort against OvCHT1 was conducted using the Johns Hopkins
      Clinical Compound Library that contains over 1,500 existing drugs. Closantel, a
      veterinary anthelmintic with known proton ionophore activities, was identified as
      a potent and specific inhibitor of filarial chitinases, an activity not
      previously reported for this compound. Notably, closantel was found also to
      completely inhibit molting of O. volvulus infective L3 stage larvae. Closantel
      appears to target two important biochemical processes essential to filarial
      parasites. To begin to unravel closantel's effects, a retro-fragment-based study
      was used to define structural elements critical for closantel's chitinase
      inhibitor function. As resources towards the development of new agents that
      target neglected tropical diseases are scant, the finding of an existing drug
      with impact against O. volvulus provides promise in the hunt for new therapies
      against river blindness.

PMID- 20142510
TI  - Gas-phase water-mediated equilibrium between methylglyoxal and its geminal diol.
AB  - In aqueous solution, aldehydes, and to a lesser extent ketones, hydrate to form
      geminal diols. We investigate the hydration of methylglyoxal (MG) in the gas
      phase, a process not previously considered to occur in water-restricted
      environments. In this study, we spectroscopically identified methylglyoxal diol
      (MGD) and obtained the gas-phase partial pressures of MG and MGD. These results,
      in conjunction with the relative humidity, were used to obtain the equilibrium
      constant, K(P), for the water-mediated hydration of MG in the gas phase. The
      Gibbs free energy for this process, DeltaG(o), obtained as a result, suggests a
      larger than expected gas-phase diol concentration. This may have significant
      implications for understanding the role of organics in atmospheric chemistry.

PMID- 20142511
TI  - In situ measurements of gas/particle-phase transitions for atmospheric
      semivolatile organic compounds.
AB  - An understanding of the gas/particle-phase partitioning of semivolatile compounds
      is critical in determining atmospheric aerosol formation processes and growth
      rates, which in turn affect global climate and human health. The Study of Organic
      Aerosol at Riverside 2005 campaign was performed to gain a better understanding
      of the factors responsible for aerosol formation and growth in Riverside, CA, a
      region with high concentrations of secondary organic aerosol formed through the
      phase transfer of low-volatility reaction products from the oxidation of
      precursor gases. We explore the ability of the thermal desorption aerosol gas
      chromatograph (TAG) to measure gas-to-particle-phase transitioning for several
      organic compound classes (polar and nonpolar) found in the ambient Riverside
      atmosphere by using in situ observations of several hundred semivolatile organic
      compounds. Here we compare TAG measurements to modeled partitioning of select
      semivolatile organic compounds. Although TAG was not designed to quantify the
      vapor phase of semivolatile organics, TAG measurements do distinguish when
      specific compounds are dominantly in the vapor phase, are dominantly in the
      particle phase, or have both phases present. Because the TAG data are both
      speciated and time-resolved, this distinction is sufficient to see the transition
      from vapor to particle phase as a function of carbon number and compound class.
      Laboratory studies typically measure the phase partitioning of semivolatile
      organic compounds by using pure compounds or simple mixtures, whereas hourly TAG
      phase partitioning measurements can be made in the complex mixture of thousands
      of polar/nonpolar and organic/inorganic compounds found in the atmosphere.

PMID- 20142512
TI  - Three-dimensional structure of the anthrax toxin pore inserted into lipid
      nanodiscs and lipid vesicles.
AB  - A major goal in understanding the pathogenesis of the anthrax bacillus is to
      determine how the protective antigen (PA) pore mediates translocation of the
      enzymatic components of anthrax toxin across membranes. To obtain structural
      insights into this mechanism, we constructed PA-pore membrane complexes and
      visualized them by using negative-stain electron microscopy. Two populations of
      PA pores were visualized in membranes, vesicle-inserted and nanodisc-inserted,
      allowing us to reconstruct two virtually identical PA-pore structures at 22-A
      resolution. Reconstruction of a domain 4-truncated PA pore inserted into
      nanodiscs showed that this domain does not significantly influence pore
      structure. Normal mode flexible fitting of the x-ray crystallographic coordinates
      of the PA prepore indicated that a prominent flange observed within the pore
      lumen is formed by the convergence of mobile loops carrying Phe427, a residue
      known to catalyze protein translocation. Our results have identified the location
      of a crucial functional element of the PA pore and documented the value of
      combining nanodisc technology with electron microscopy to examine the structures
      of membrane-interactive proteins.

PMID- 20142513
TI  - Structural basis for the cooperative interplay between the two causative gene
      products of combined factor V and factor VIII deficiency.
AB  - Combined deficiency of coagulation factors V and VIII (F5F8D), an autosomal
      recessive disorder characterized by coordinate reduction in the plasma levels of
      factor V (FV) and factor VIII (FVIII), is genetically linked to mutations in the
      transmembrane lectin ERGIC-53 and the soluble calcium-binding protein MCFD2.
      Growing evidence indicates that these two proteins form a complex recycling
      between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment
      and thereby function as a cargo receptor in the early secretory pathway of FV and
      FVIII. For better understanding of the mechanisms underlying the functional
      coordination of ERGIC-53 and MCFD2, we herein characterize their interaction by x
      ray crystallographic analysis in conjunction with NMR and ultracentrifugation
      analyses. Inspection of the combined data reveals that ERGIC-53-CRD binds MCFD2
      through its molecular surface remote from the sugar-binding site, giving rise to
      a 11 complex in solution. The interaction is independent of sugar-binding of
      ERGIC-53 and involves most of the missense mutation sites of MCFD2 so far
      reported in F5F8D. Comparison with the previously reported uncomplexed structure
      of each protein indicates that MCFD2 but not ERGIC-53-CRD undergoes significant
      conformational alterations upon complex formation. Our findings provide a
      structural basis for the cooperative interplay between ERGIC-53 and MCFD2 in
      capturing FV and FVIII.

PMID- 20142514
TI  - Independent initiation of primary electron transfer in the two branches of the
      photosystem I reaction center.
AB  - Photosystem I (PSI) is a large pigment-protein complex that unites a reaction
      center (RC) at the core with approximately 100 core antenna chlorophylls
      surrounding it. The RC is composed of two cofactor branches related by a pseudo
      C2 symmetry axis. The ultimate electron donor, P(700) (a pair of chlorophylls),
      and the tertiary acceptor, F(X) (a Fe(4)S(4) cluster), are both located on this
      axis, while each of the two branches is made up of a pair of chlorophylls (ec2
      and ec3) and a phylloquinone (PhQ). Based on the observed biphasic reduction of
      F(X), it has been suggested that both branches in PSI are competent for electron
      transfer (ET), but the nature and rate of the initial electron transfer steps
      have not been established. We report an ultrafast transient absorption study of
      Chlamydomonas reinhardtii mutants in which specific amino acids donating H-bonds
      to the 13(1)-keto oxygen of either ec3(A) (PsaA-Tyr696) or ec3(B) (PsaB-Tyr676)
      are converted to Phe, thus breaking the H-bond to a specific ec3 cofactor. We
      find that the rate of primary charge separation (CS) is lowered in both mutants,
      providing direct evidence that the primary ET event can be initiated
      independently in each branch. Furthermore, the data provide further support for
      the previously published model in which the initial CS event occurs within an
      ec2/ec3 pair, generating a primary ec2(+)ec3(-) radical pair, followed by rapid
      reduction by P(700) in the second ET step. A unique kinetic modeling approach
      allows estimation of the individual ET rates within the two cofactor branches.

PMID- 20142515
TI  - Heterospecies partition analysis reveals binding curve and stoichiometry of
      protein interactions in living cells.
AB  - Measuring the binding curve and stoichiometry of protein complexes in living
      cells is a prerequisite for quantitative modeling of cellular processes. Dual
      color fluorescence fluctuation spectroscopy provides a general framework for
      detecting protein interactions, but lacks suitable methods for quantifying
      protein heterointeractions in the cell. We address this challenge by introducing
      heterospecies partition (HSP) analysis for protein heterointeractions of the type
      D + nA<-->DA(n). HSP directly identifies the heterointeracting species from the
      sample mixture and determines the binding curve and stoichiometry of the protein
      complex. The HSP method is applied to provide the first direct characterization
      of the ligand-dependent binding of the retinoic X receptor to the coactivator
      transcription intermediate factor 2. A previous study based on protein fragments
      observed a higher binding stoichiometry than biologically expected. We address
      this difference in stoichiometry by measuring the binding curves of the full
      length proteins in living cells. This study provides proof-of-principle
      experiments that illustrate the potential of HSP as a general and robust analysis
      tool for the quantitative characterization of protein heterointeractions by dual
      color fluorescence fluctuation spectroscopy in living cells.

PMID- 20142516
TI  - Regulation of conductance by the number of fixed positive charges in the
      intracellular vestibule of the CFTR chloride channel pore.
AB  - Rapid chloride permeation through the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl(-) channel is dependent on the presence of fixed positive
      charges in the permeation pathway. Here, we use site-directed mutagenesis and
      patch clamp recording to show that the functional role played by one such
      positive charge (K95) in the inner vestibule of the pore can be "transplanted" to
      a residue in a different transmembrane (TM) region (S1141). Thus, the mutant
      channel K95S/S1141K showed Cl(-) conductance and open-channel blocker
      interactions similar to those of wild-type CFTR, thereby "rescuing" the effects
      of the charge-neutralizing K95S mutation. Furthermore, the function of
      K95C/S1141C, but not K95C or S1141C, was inhibited by the oxidizing agent
      copper(II)-o-phenanthroline, and this inhibition was reversed by the reducing
      agent dithiothreitol, suggesting disulfide bond formation between these two
      introduced cysteine side chains. These results suggest that the amino acid side
      chains of K95 (in TM1) and S1141 (in TM12) are functionally interchangeable and
      located closely together in the inner vestibule of the pore. This allowed us to
      investigate the functional effects of increasing the number of fixed positive
      charges in this vestibule from one (in wild type) to two (in the S1141K mutant).
      The S1141K mutant had similar Cl(-) conductance as wild type, but increased
      susceptibility to channel block by cytoplasmic anions including adenosine
      triphosphate, pyrophosphate, 5-nitro-2-(3-phenylpropylamino)benzoic acid, and
      Pt(NO(2))(4)(2-) in inside-out membrane patches. Furthermore, in cell-attached
      patch recordings, apparent voltage-dependent channel block by cytosolic anions
      was strengthened by the S1141K mutation. Thus, the Cl(-) channel function of CFTR
      is maximal with a single fixed positive charge in this part of the inner
      vestibule of the pore, and increasing the number of such charges to two causes a
      net decrease in overall Cl(-) transport through a combination of failure to
      increase Cl(-) conductance and increased susceptibility to channel block by
      cytosolic substances.

PMID- 20142517
TI  - Molecular endpoints of Ca2+/calmodulin- and voltage-dependent inactivation of
      Ca(v)1.3 channels.
AB  - Ca(2+)/calmodulin- and voltage-dependent inactivation (CDI and VDI) comprise
      vital prototypes of Ca(2+) channel modulation, rich with biological consequences.
      Although the events initiating CDI and VDI are known, their downstream mechanisms
      have eluded consensus. Competing proposals include hinged-lid occlusion of
      channels, selectivity filter collapse, and allosteric inhibition of the
      activation gate. Here, novel theory predicts that perturbations of channel
      activation should alter inactivation in distinctive ways, depending on which
      hypothesis holds true. Thus, we systematically mutate the activation gate, formed
      by all S6 segments within Ca(V)1.3. These channels feature robust baseline CDI,
      and the resulting mutant library exhibits significant diversity of activation,
      CDI, and VDI. For CDI, a clear and previously unreported pattern emerges:
      activation-enhancing mutations proportionately weaken inactivation. This outcome
      substantiates an allosteric CDI mechanism. For VDI, the data implicate a "hinged
      lid-shield" mechanism, similar to a hinged-lid process, with a previously
      unrecognized feature. Namely, we detect a "shield" in Ca(V)1.3 channels that is
      specialized to repel lid closure. These findings reveal long-sought downstream
      mechanisms of inactivation and may furnish a framework for the understanding of
      Ca(2+) channelopathies involving S6 mutations.

PMID- 20142518
TI  - Systematic mapping of the state dependence of voltage- and Ca2+-dependent
      inactivation using simple open-channel measurements.
AB  - The state from which channel inactivation occurs is both biologically and
      mechanistically critical. For example, preferential closed-state inactivation is
      potentiated in certain Ca(2+) channel splice variants, yielding an enhancement of
      inactivation during action potential trains, which has important consequences for
      short-term synaptic plasticity. Mechanistically, the structural substrates of
      inactivation are now being resolved, yielding a growing library of molecular
      snapshots, ripe for functional interpretation. For these reasons, there is an
      increasing need for experimentally direct and systematic means of determining the
      states from which inactivation proceeds. Although many approaches have been
      devised, most rely upon numerical models that require detailed knowledge of
      channel-state topology and gating parameters. Moreover, prior strategies have
      only addressed voltage-dependent forms of inactivation (VDI), and have not been
      readily applicable to Ca(2+)-dependent inactivation (CDI), a vital form of
      regulation in numerous contexts. Here, we devise a simple yet systematic
      approach, applicable to both VDI and CDI, for semiquantitative mapping of the
      states from which inactivation occurs, based only on open-channel measurements.
      The method is relatively insensitive to the specifics of channel gating and does
      not require detailed knowledge of state topology or gating parameters. Rather
      than numerical models, we derive analytic equations that permit determination of
      the states from which inactivation occurs, based on direct manipulation of data.
      We apply this methodology to both VDI and CDI of Ca(V)1.3 Ca(2+) channels. VDI is
      found to proceed almost exclusively from the open state. CDI proceeds equally
      from the open and nearby closed states, but is disfavored from deep closed states
      distant from the open conformation. In all, these outcomes substantiate and
      enrich conclusions of our companion paper in this issue (Tadross et al. 2010. J.
      Gen. Physiol. doi:10.1085/jgp.200910308) that deduces endpoint mechanisms of VDI
      and CDI in Ca(V)1.3. More broadly, the methods introduced herein can be readily
      generalized for the analysis of other channel types.

PMID- 20142519
TI  - Clinical effect of neutralizing antibodies to interferon beta that persist long
      after cessation of therapy for multiple sclerosis.
AB  - OBJECTIVES: To confirm that neutralizing antibodies (NAb) to interferon beta can
      persist after therapy withdrawal and to evaluate whether persisting NAb are
      associated with a worse clinical disease course in multiple sclerosis (MS).
      DESIGN: Retrospective study. SETTING: Tertiary referral center in The
      Netherlands. PATIENTS: A total of 71 patients with relapsing-remitting multiple
      sclerosis treated with interferon beta in the past. MAIN OUTCOME MEASURES:
      Persisting NAb after therapy withdrawal were tested using the cytopathic effect
      assay. Patients with and without persisting NAb were compared on several
      outcomes: the change in annualized relapse rate from prior to interferon beta
      treatment initiation to after cessation of treatment, time to sustained
      disability on the Kurtzke Expanded Disability Status Scale, and the use of
      disease-modifying treatments after cessation of treatment with interferon beta.
      RESULTS: Seventeen of 71 patients (24%) tested NAb positive after a median
      interval of 25 months (interquartile range, 10-51 months) after interferon beta
      treatment cessation. Eleven of these 17 patients (15%) were high-titer NAb
      positive (>150 10-fold reduction units per mL). Persisting NAb were associated
      with an increase in the annualized relapse rate (P = .04) and a reduction in time
      to reach a sustained Expanded Disability Status Scale score of 6.0, ie, the need
      for unilateral assistance to walk 100 m (P = .02). Moreover, NAb-positive
      patients were treated with second-line therapy significantly more often,
      especially mitoxantrone (P = .006). CONCLUSION: Anti-interferon beta NAb can
      persist after interferon beta treatment withdrawal and are associated with overt
      clinical disease activity. This is made apparent by an increase in relapse rate
      and faster disability progression and is supported by the observed need for more
      aggressive therapy after interferon beta treatment cessation. Prospective studies
      are warranted to confirm these results.

PMID- 20142521
TI  - Progress on progranulin.

PMID- 20142520
TI  - Laser photocoagulation, photodynamic therapy, and intravitreal bevacizumab for
      the treatment of juxtafoveal choroidal neovascularization secondary to pathologic
      myopia.
AB  - OBJECTIVE: To compare the effects on visual acuity of laser treatment (LT),
      photodynamic therapy (PDT) with verteporfin, and intravitreal bevacizumab
      treatment in patients with juxtafoveal choroidal neovascularization secondary to
      pathologic myopia. METHODS: This prospective randomized clinical investigation
      enrolled 54 patients, who were divided into 3 groups receiving PDT, LT, or
      intravitreal bevacizumab treatment. The anti-vascular endothelial growth factor
      group received 1.25 mg of intravitreal bevacizumab at baseline; retreatment was
      performed if persistent intraretinal or subretinal fluid evaluated on optical
      coherence tomography or if choroidal neovascularization progression was detected
      on fluorescein angiography. The PDT group received treatment following the
      Verteporfin in Photodynamic Therapy Study Group guidelines. The LT group was
      submitted to direct LT and received PDT treatment if subfoveal recurrence or
      progression was detected on fluorescein angiography. A change in best-corrected
      visual acuity was the primary outcome. RESULTS: The mean best-corrected visual
      acuity in the PDT group decreased from 0.52 logMAR (SD, 0.24 logMAR) at baseline
      to 0.72 logMAR (SD, 0.25 logMAR) at the end of the study (P = .002). The LT group
      showed substantial stabilization from mean baseline visual acuity (mean, 0.45
      logMAR [SD, 0.27 logMAR]) to the 24-month (mean, 0.56 logMAR [SD, 0.34 logMAR)
      examination values. The mean best-corrected visual acuity in the anti-vascular
      endothelial growth factor group increased from 0.6 logMAR (SD, 0.3 logMAR) at
      baseline to 0.42 logMAR (SD, 0.35 logMAR) at the end of the study (P = .006).
      CONCLUSIONS: Overall, bevacizumab treatment offers the best functional results
      during a 2-year follow-up. In view of the small size of the sample in this study
      and the relatively low frequency of juxtafoveal choroidal neovascularization
      secondary to pathologic myopia, a multicentric clinical trial is necessary to
      validate our results.

PMID- 20142522
TI  - Inherited metabolic disorders and stroke part 2: homocystinuria, organic
      acidurias, and urea cycle disorders.
AB  - Several inherited metabolic disorders have been associated with stroke
      particularly in newborns, children, and young adults. In part 1, we discussed the
      genetics, stroke pathophysiology, clinical presentation, diagnosis, and treatment
      of Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis, and
      strokelike episodes. In part 2, we overview homocystinuria, organic acidurias,
      and urea cycle disorders.

PMID- 20142523
TI  - A randomized, placebo-controlled trial of latrepirdine in Huntington disease.
AB  - OBJECTIVES: To evaluate the safety and tolerability of latrepirdine in Huntington
      disease (HD) and explore its effects on cognition, behavior, and motor symptoms.
      DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Multicenter
      outpatient trial. PARTICIPANTS: Ninety-one participants with mild to moderate HD
      enrolled at 17 US and UK centers from July 18, 2007, through July 16, 2008.
      INTERVENTION: Latrepirdine, 20 mg 3 times daily (n = 46), or matching placebo (n
      = 45) for a 90-day treatment period. MAIN OUTCOME MEASURES: The primary outcome
      variable was tolerability, defined as the ability to complete the study at the
      assigned drug dosage. Secondary outcome variables included score changes from
      baseline to day 90 on the Unified Huntington's Disease Rating Scale (UHDRS), the
      Mini-Mental State Examination (MMSE), and the Alzheimer Disease Assessment Scale
      cognitive subscale (ADAS-cog). RESULTS: Latrepirdine was well tolerated (87% of
      the patients given latrepirdine completed the study vs 82% in the placebo group),
      and adverse event rates were comparable in the 2 groups (70% in the latrepirdine
      group and 80% in the placebo group). Treatment with latrepirdine resulted in
      improved mean MMSE scores compared with stable performance in the placebo group
      (treatment effect, 0.97 points; 95% confidence interval, 0.10-1.85; P = .03). No
      significant treatment effects were seen on the UHDRS or the ADAS-cog.
      CONCLUSIONS: Short-term administration of latrepirdine is well tolerated in
      patients with HD and may have a beneficial effect on cognition. Further
      investigation of latrepirdine is warranted in this population with HD.

PMID- 20142524
TI  - The spectrum of mutations in progranulin: a collaborative study screening 545
      cases of neurodegeneration.
AB  - BACKGROUND: Mutation in the progranulin gene (GRN) can cause frontotemporal
      dementia (FTD). However, it is unclear whether some rare FTD-related GRN variants
      are pathogenic and whether neurodegenerative disorders other than FTD can also be
      caused by GRN mutations. OBJECTIVES: To delineate the range of clinical
      presentations associated with GRN mutations and to define pathogenic candidacy of
      rare GRN variants. DESIGN: Case-control study. SETTING: Clinical and
      neuropathology dementia research studies at 8 academic centers. PARTICIPANTS:
      Four hundred thirty-four patients with FTD, including primary progressive
      aphasia, semantic dementia, FTD/amyotrophic lateral sclerosis (ALS), FTD/motor
      neuron disease, corticobasal syndrome/corticobasal degeneration, progressive
      supranuclear palsy, Pick disease, dementia lacking distinctive histopathology,
      and pathologically confirmed cases of frontotemporal lobar degeneration with
      ubiquitin-positive inclusions (FTLD-U); and 111 non-FTD cases (controls) in which
      TDP-43 deposits were a prominent neuropathological feature, including subjects
      with ALS, Guam ALS and/or parkinsonism dementia complex, Guam dementia, Alzheimer
      disease, multiple system atrophy, and argyrophilic grain disease. MAIN OUTCOME
      MEASURES: Variants detected on sequencing of all 13 GRN exons and at least 80
      base pairs of flanking introns, and their pathogenic candidacy determined by in
      silico and ex vivo splicing assays. RESULTS: We identified 58 genetic variants
      that included 26 previously unknown changes. Twenty-four variants appeared to be
      pathogenic, including 8 novel mutations. The frequency of GRN mutations was 6.9%
      (30 of 434) of all FTD-spectrum cases, 21.4% (9 of 42) of cases with a
      pathological diagnosis of FTLD-U, 16.0% (28 of 175) of FTD-spectrum cases with a
      family history of a similar neurodegenerative disease, and 56.2% (9 of 16) of
      cases of FTLD-U with a family history. CONCLUSIONS: Pathogenic mutations were
      found only in FTD-spectrum cases and not in other related neurodegenerative
      diseases. Haploinsufficiency of GRN is the predominant mechanism leading to FTD.

PMID- 20142525
TI  - Alzheimer disease-like phenotype associated with the c.154delA mutation in
      progranulin.
AB  - OBJECTIVE: To characterize a kindred with a familial neurodegenerative disorder
      associated with a mutation in progranulin (PGRN), with emphasis on the unique
      clinical features in this kindred. DESIGN: Antemortem and postmortem
      characterization of a kindred with a familial neurodegenerative disorder.
      SETTING: Multispecialty group academic medical center. PATIENTS: Affected members
      of a kindred with dementia with or without parkinsonism associated with a unique
      mutation in PGRN. MAIN OUTCOME MEASURE: Genotype-phenotype correlation. RESULTS:
      Of 10 affected individuals identified, 6 presented with early amnestic symptoms
      which resulted in initial diagnoses of Alzheimer disease or amnestic mild
      cognitive impairment. Some individuals presented with features characteristic of
      frontotemporal dementia. Mean age at onset was substantially younger in
      generation III (75.8 years; range, 69-80 years) than in generation II (60.7
      years; range, 55-66 years). The pattern of cerebral atrophy varied widely in the
      affected individuals. Neuropathologic features in 6 individuals included
      frontotemporal lobar degeneration with ubiquitin-positive neuronal cytoplasmic
      and intranuclear inclusions (FTLD-U with NII). PGRN analysis revealed a single
      base pair deletion in exon 2 (c.154delA), which caused a frameshift
      (p.Thr52HisfsX2) and, therefore, creation of a premature termination codon and a
      likely null allele. CONCLUSIONS: In this large kindred, most affected individuals
      had clinical presentations that resembled Alzheimer disease or amnestic mild
      cognitive impairment associated with a mutation in PGRN and underlying FTLD-U
      with NII neuropathologic abnormalities. This finding is in distinct contrast to
      previously reported kindreds, in which clinical presentations have typically been
      within the spectrum of FTLD. The basis for the large difference in age at onset
      between generations requires further study.

PMID- 20142526
TI  - Hypertension, executive dysfunction, and progression to dementia: the canadian
      study of health and aging.
AB  - BACKGROUND: Midlife hypertension has long been established as a risk factor for
      dementia, but the role of late-life hypertension remains unclear. OBJECTIVE: To
      investigate the role of hypertension in cognitive deterioration among older
      subjects with cognitive impairment, no dementia. DESIGN: The Canadian Study of
      Health and Aging was conducted in 3 waves (1991, 1995-1996, and 2001-2002).
      SETTING: Community-based cohort study. PATIENTS: We studied 990 subjects with a
      mean (SD) age of 83.06 (6.97) years having cognitive impairment, no dementia who
      were followed up for 5 years in the Canadian Study of Health and Aging. MAIN
      OUTCOME MEASURES: Determination of cognitive dysfunction and association between
      hypertension and cognitive deterioration. RESULTS: No difference in the rate of
      progression to dementia based on the presence of hypertension was found between
      subjects with memory dysfunction alone or in combination with executive
      dysfunction. However, among subjects with executive dysfunction alone, 57.7%
      having hypertension progressed to dementia compared with 28.0% having
      normotension (P = .02). CONCLUSIONS: Hypertension predicts progression to
      dementia in older subjects with executive dysfunction but not memory dysfunction.
      Control of hypertension could prevent progression to dementia in one-third of the
      subjects with cognitive impairment, no dementia.

PMID- 20142528
TI  - Autoantibody-mediated dysfunction of sympathetic neurons in guillain-barre
      syndrome.
AB  - OBJECTIVE: To investigate a pathologic immune response to autonomic nerve fibers
      in Guillain-Barre syndrome (GBS). DESIGN: We compared the effects of purified IgG
      from patients with GBS, multiple sclerosis, and chronic inflammatory
      demyelinating polyneuropathy on transmitter synthesis and synaptic transmission
      in an in vitro model of sympathetic neurons and cardiomyocytes. SUBJECTS: Three
      patients with GBS, 2 with chronic inflammatory demyelinating
      polyradiculoneuropathy, and 2 with relapsing-remitting multiple sclerosis.
      RESULTS: Incubation of sympathetic neurons with GBS-IgG resulted in an
      upregulation of tyrosine hydroxylase and caused a relative increase of
      noradrenaline levels. In cocultures of sympathetic neurons and cardiomyocytes,
      GBS-IgG altered the synaptic transmission, as assessed by changes in the average
      cardiomyocyte beat rate. These effects could be neutralized by preincubation of
      sympathetic neurons with intravenous immunoglobulins. CONCLUSION: Our findings
      indicate that in GBS, circulating antibodies directed against sympathetic neurons
      may contribute to autonomic dysfunction via functionally relevant changes in the
      noradrenaline synthesis.

PMID- 20142527
TI  - Prospective study of endogenous circulating estradiol and risk of stroke in older
      women.
AB  - OBJECTIVE: To test the hypothesis that circulating endogenous estradiol is
      associated with stroke risk in older postmenopausal women. Stroke incidence
      increases after menopause, when endogenous estrogen levels fall, yet exogenous
      estrogen increases strokes in older postmenopausal women. The relation between
      endogenous estrogen and stroke is unclear. DESIGN: Prospective case-control
      study. SETTING: Study of Osteoporotic Fractures. PATIENTS OR OTHER PARTICIPANTS:
      Women at least age 65 years (99% follow-up) who were not taking estrogen at
      baseline. MAIN OUTCOME MEASURES: Free estradiol index (FEI) was calculated by
      dividing total estradiol by sex hormone-binding globulin concentrations measured
      in banked baseline serum. Using logistic regression, odds ratios were estimated
      for a first-ever atherothrombotic stroke associated with endogenous FEI in 196
      women who had a subsequent validated stroke (median follow-up, 8 years) compared
      with 219 randomly selected women who did not. Potential mediators were assessed
      in multivariable models. RESULTS: The age-adjusted odds of atherothrombotic
      stroke increased with increasing FEI quartiles (P(trend) = .007). Women in the
      highest FEI quartile had an age-adjusted 2.31-fold (odds ratio, 2.31; 95%
      confidence interval, 1.28-4.17) higher odds than women in the lowest quartile.
      Women with greater central adiposity had a suggestively stronger association (P =
      .08). Atherogenic dyslipidemia, type 2 diabetes mellitus, and C-reactive protein
      level were potential mediators of this relation. CONCLUSIONS: Endogenous
      estradiol level is an indicator of stroke risk in older postmenopausal women,
      especially in those with greater central adiposity. Potential mediators,
      including atherogenic dyslipidemia, insulin resistance, and inflammation, might
      underlie this association. Whether estradiol, independent of atherogenic
      adiposity, influences such mediators and stroke risk needs to be determined.
      Estrogen-altering agents might be harmful or beneficial depending on endogenous
      estradiol levels, especially in women with greater central adiposity.

PMID- 20142530
TI  - Correlation of longitudinal cerebrospinal fluid biomarkers with cognitive decline
      in healthy older adults.
AB  - BACKGROUND: Abnormal cerebrospinal fluid (CSF) biomarker levels predict
      development of Alzheimer disease with good accuracy and are thought to precede
      cognitive deterioration. OBJECTIVE: To investigate whether changes in CSF
      biomarker levels over time in healthy older adults are associated with a
      concurrent decline in cognitive performance. DESIGN: Retrospective analysis of
      longitudinal CSF biomarker levels and clinical data. SETTING: A combined academic
      dementia disorder research center and dementia clinic. PARTICIPANTS: Thirty-seven
      cognitively healthy older volunteers (mean age, 73 years). MAIN OUTCOME MEASURES:
      Longitudinal CSF total tau protein, hyperphosphorylated tau protein 181, and beta
      amyloid(1-42) protein levels and cognitive assessments at baseline and at follow
      up 4 years later. RESULTS: Low levels of CSF beta-amyloid(1-42) protein at follow
      up were associated with decreased delayed word recall score on the Alzheimer
      Disease Assessment Scale-cognitive subscale (r(s) = -0.437, P < .01) and with
      slower results on A Quick Test of Cognitive Speed (r(s) = -0.540, P < .001).
      Individuals with a decrease during the 4-year study of 15% or more in CSF beta
      amyloid(1-42) protein level performed worse on the Alzheimer Disease Assessment
      Scale-cognitive subscale delayed word recall (z = -2.18, P < .05) and A Quick
      Test of Cognitive Speed (z = -2.35, P < .05) at follow-up. An increase over time
      of 20% or more in CSF hyperphosphorylated tau protein 181 level correlated with
      slower results on A Quick Test of Cognitive Speed at follow-up (z = -2.13, P <
      .05). Furthermore, the presence of the APOE-epsilon4 (OMIM 107741) allele was
      associated with a greater longitudinal decrease in CSF beta-amyloid(1-42) protein
      level (chi(2) = 10.47, P < .05) and with a higher CSF total tau protein level at
      follow-up (chi(2) = 8.83, P < .05). No correlation existed between baseline CSF
      biomarker levels and baseline or follow-up cognitive scores. CONCLUSIONS: In this
      group of healthy older adults, changes in CSF biomarker levels previously
      associated with Alzheimer disease correlated with a decline in cognitive
      functions. Changes in CSF biomarker levels may identify early neurodegenerative
      processes of Alzheimer disease.

PMID- 20142529
TI  - Ventilatory and cardiovascular responses to hypercapnia and hypoxia in multiple
      system atrophy.
AB  - BACKGROUND: Loss of medullary sympathoexcitatory neurons may contribute to
      baroreflex failure, leading to orthostatic hypotension in multiple-system atrophy
      (MSA). The cardiovascular responses to chemoreflex activation in MSA have not
      been explored to date. OBJECTIVES: To determine whether ventilatory and
      cardiovascular responses to hypercapnia and hypoxia during wakefulness are
      systematically impaired in MSA. DESIGN: Case-control study. SETTING: Mayo Clinic,
      Rochester, Minnesota. PATIENTS: Sixteen patients with probable MSA (cases) and 14
      age-matched control subjects (controls). MAIN OUTCOME MEASURES: Minute
      ventilation, blood pressure, and heart rate responses to hypercapnia and hypoxia
      during wakefulness. Hypercapnia was induced by a rebreathing technique and was
      limited to a maximal expiratory partial pressure of carbon dioxide of 65 mm Hg.
      Hypoxia was induced by a stepwise increase in inspiratory partial pressure of
      nitrogen and was limited to a minimal arterial oxygen saturation of 80%.
      Ventilatory responses were assessed as slopes of the regression line relating
      minute ventilation to changes in arterial oxygen saturation and partial pressure
      of carbon dioxide. RESULTS: In cases, ventilatory responses to hypercapnia and
      hypoxia were preserved, despite the presence of severe autonomic failure, while
      cardiovascular responses to these stimuli were impaired. Among cases, hypercapnia
      elicited a less robust increase in arterial pressure than among controls, and
      hypoxia elicited a depressor response rather than the normal pressor responses (P
      < .001 for both). CONCLUSIONS: Ventilatory responses to hypercapnia and hypoxia
      during wakefulness may be preserved in patients with MSA, despite the presence of
      autonomic failure and impaired cardiovascular responses to these stimuli. A
      critical number of chemosensitive medullary neurons may need to be lost before
      development of impaired automatic ventilation during wakefulness in MSA, whereas
      earlier loss of medullary sympathoexcitatory neurons may contribute to the
      impaired cardiovascular responses in these patients.

PMID- 20142531
TI  - FUS mutations in familial amyotrophic lateral sclerosis in the Netherlands.
AB  - OBJECTIVES: To assess the frequency of FUS mutations in 52 probands with familial
      amyotrophic lateral sclerosis (FALS) and to provide careful documentation of
      clinical characteristics. DESIGN: FUS mutation analysis was performed using
      capillary sequencing on all coding regions of the gene in a cohort of patients
      with FALS. The clinical characteristics of patients carrying FUS mutations were
      described in detail. SETTING: Three university hospitals in the Netherlands
      (referral centers for neuromuscular diseases). PATIENTS: Fifty-two probands from
      unrelated pedigrees with FALS. MAIN OUTCOME MEASURE: FUS mutations. RESULTS: We
      identified 3 mutations in 4 of 52 probands. We observed 2 previously identified
      mutations (p.Arg521Cys and p.Arg521His) and 1 novel mutation (p.Ser462Phe). In
      addition, a p.Gln210His polymorphism was identified in 1 proband and 3 healthy
      control subjects. Phenotypic analysis demonstrated that patients may lack upper
      motor neuron signs, which was confirmed at autopsy, and disease survival was
      short (<36 months for 8 of 10 patients). CONCLUSIONS: We discovered FUS mutations
      in Dutch patients with FALS and the occurrence of benign variations in the gene.
      Therefore, caution is warranted when interpreting results in a clinical setting.
      Although the phenotype associated with FUS mutations is variable, most patients
      predominantly demonstrate loss of lower motor neurons and have short disease
      survival.

PMID- 20142532
TI  - Scoliosis surgery in children with neuromuscular disease: findings from the US
      National Inpatient Sample, 1997 to 2003.
AB  - BACKGROUND: Scoliosis is a frequent complication of pediatric neuromuscular
      disease (NMD). Scoliosis surgery in children with NMD is thought to carry greater
      morbidity and mortality. OBJECTIVES: To study demographics, comorbidities,
      outcomes, and hospitalization expenditures among children with NMD undergoing
      scoliosis surgery. DESIGN: Using the Kids Inpatient Database, a large all-payer
      US database of hospital discharges among children and adults younger than 20
      years, we studied children undergoing scoliosis surgery between January 1, 1997,
      and December 31, 2003. Continuous variables were compared by t test, and
      categorical variables were compared by Pearson product moment correlation chi(2)
      test. SETTING: National database of pediatric hospital discharges. PATIENTS:
      Children with and without NMD. MAIN OUTCOME MEASURES: Demographics, hospital
      length of stay, and in-hospital mortality associated with scoliosis surgery.
      RESULTS: Of 17 780 reported hospitalizations owing to scoliosis surgery, 437
      children (2.5%) had NMD. Compared with children undergoing scoliosis surgery for
      other indications, children with NMD were more likely to be younger (12.4 vs 14.2
      years), male (73.5% vs 38.3%), and insured by Medicaid (35.6% vs 20.3%).
      Comorbidities that were more common among children with NMD included pulmonary
      complications (lung disease not classified, pulmonary collapse, pulmonary
      insufficiency, chronic respiratory failure, and ventilator requirement) and
      cardiovascular complications (cardiomyopathy, hypotension, and tachycardia).
      Scoliosis surgery in children with NMD was associated with increased hospital
      length of stay (10.3 vs 7.7 days) and hospitalization expenditures ($80 251 vs
      $62 154), and higher in-hospital mortality (1.6% vs 0.2%). CONCLUSION: Children
      with NMD have increased hospital length of stay and higher in-hospital mortality
      associated with scoliosis surgery, highlighting the need for further study of
      measures that could reduce complications and improve outcomes in this population.

PMID- 20142533
TI  - Intraparenchymal hemorrhage in a patient with osteogenesis imperfecta and
      plasminogen activator inhibitor-1 deficiency.
AB  - BACKGROUND: Osteogenesis imperfecta is associated with susceptibility to
      connective tissue damage, including intracranial but usually extra-axial
      hemorrhage. Plasminogen activator inhibitor-1 deficiency is a rare fibrinolytic
      cause of systemic bleeding diathesis. OBJECTIVE: To describe a case of a
      brainstem intraparenchymal hemorrhage associated with connective tissue and
      coagulation disorders. DESIGN: Case report. SETTING: Academic medical center.
      PATIENT: A 36-year-old woman with a history of osteogenesis imperfecta presented
      to the emergency department after an argument, during which she developed left
      ear pain and right eye esotropia followed by quadriparesis and somnolence.
      Neuroimaging showed a tegmental mesencephalic hemorrhage. MAIN OUTCOME MEASURES:
      Results of computerized tomography, magnetic resonance angiography, and
      parenchymal imaging; and serum hematologic markers. RESULTS: No underlying
      vascular abnormality or mass lesion was found. Among coagulopathic serum markers,
      only plasminogen activator inhibitor-1 activity level was abnormally low.
      CONCLUSION: Intraparenchymal hemorrhage may occur in the setting of a
      fibrinolytic inhibitory deficiency and osteogenesis imperfecta.

PMID- 20142535
TI  - Acute bilateral basal ganglia lesions and chorea in a diabetic-uremic patient on
      dialysis.

PMID- 20142534
TI  - A novel POLG gene mutation in 4 children with Alpers-like hepatocerebral
      syndromes.
AB  - OBJECTIVE: To describe a novel POLG missense mutation (c.3218C>T; p.P1073L) that,
      in association with 2 previously described mutations, caused an Alpers-like
      hepatocerebral syndrome in 4 children. DESIGN: Genotype-phenotype correlation.
      SETTING: Tertiary care universities. PATIENTS: Four children, 2 related and 2
      unrelated, with the novel p.P1073L mutation (all patients) and either the p.A467T
      (2 patients), p.G848S (1 patient), or p.W748S (1 patient) mutation presented with
      psychomotor delay, encephalopathy, and liver failure. INTERVENTIONS: Detailed
      clinical and laboratory examinations including brain magnetic resonance imaging,
      muscle biopsy, measurement of mitochondrial DNA, and sequencing of the POLG gene.
      MAIN OUTCOME MEASURES: Definition of clinical variability. RESULTS: All 4
      patients had psychomotor delay, seizures, and liver disease. Three patients had
      severe gastrointestinal dysmotility, which may be associated with the new
      p.P1073L mutation. CONCLUSIONS: The heterozygous presence of the novel p.P1073L
      mutation in trans with another recessive POLG mutation causes a hepatocerebral
      disorder identical or very similar to Alpers syndrome. This adds to the already
      striking clinical heterogeneity of POLG mutations. In the Belgian patients, the
      familial occurrence without consanguinity is related to the high frequency of the
      recessive p.A467T and p.W748S mutations in northwestern Europe and reveals a
      pitfall for diagnosis and genetic counseling.

PMID- 20142536
TI  - A very small but very symptomatic vertebral artery dissection.

PMID- 20142537
TI  - Anti-N-methyl-D-aspartate receptor encephalitis: characteristic behavioral and
      movement disorder.

PMID- 20142539
TI  - Immunohistochemical studies of conjunctival nevi and melanomas.
AB  - OBJECTIVE: To evaluate the role of immunohistochemical methods in the diagnosis
      of benign and malignant conjunctival melanocytic proliferations. DESIGN:
      Retrospective immunohistopathologic study. METHODS: Paraffin-embedded tissue
      sections from 20 conjunctival nevi and 15 invasive melanomas were immunoreacted
      with antibodies against cellular antigens S-100 protein, MART-1, HMB-45, CD-45,
      and Ki-67 nuclear proliferation protein. RESULTS: All nevi immunostained
      moderately to strongly for S-100 protein and MART-1. Results for HMB-45 were
      negative in the middle and lower subepithelial portions of 18 of 20 lesions; it
      was usually only weakly positive within the superficial junctional zone. Only 1
      melanoma did not stain positively for S-100; MART-1 and HMB-45 were positive in
      all lesions at some level of intensity. Ki-67 positivity was restricted to the
      junctional zone of nevi and was diffuse in melanomas. The mean Ki-67
      proliferation indices were 1.89% for the nevi and 17.3% for the melanomas. CD-45
      can help to highlight lymphocytes that immunostain with Ki-67. Melanomas in situ
      and atypical primary acquired melanoses had more than twice the Ki-67
      proliferation counts of intraepithelial junctional nevocytes (P < .001) and more
      intense HMB-45 cytoplasmic staining than junctional zone nevocytes. CONCLUSIONS:
      S-100 and MART-1 were not useful in separating benign from malignant lesions.
      Results for nevus cells beneath the junctional zone were overwhelmingly negative
      for HMB-45 and Ki-67. Two nevi and all melanomatous nodules were positive for HMB
      45 (P < .001). A higher Ki-67 proliferation index convincingly separated
      melanomas from nevi (P < .001). Immunostaining for HMB-45 and Ki-67 are valuable
      adjuncts to careful histopathologic evaluation in assessing benign and malignant
      conjunctival melanocytic tumors.

PMID- 20142540
TI  - New insights into changes in corneal thickness in healthy mountaineers during a
      very-high-altitude climb to Mount Muztagh Ata.
AB  - OBJECTIVE: To investigate the effect of very high altitude and different ascent
      profiles on central corneal thickness (CCT). METHODS: Twenty-eight healthy
      mountaineers were randomly assigned to 2 different ascent profiles during a
      medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group
      1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main
      outcome measure was CCT. Secondary outcome measures were oxygen saturation
      (SpO(2)) and symptom assessments of acute mountain sickness (cerebral acute
      mountain sickness score). Examinations were performed at 490, 4497, 5533, and
      6265 m. RESULTS: Central corneal thickness increased in both groups with
      increasing altitude and decreased after descent. In group 1 (with the shorter
      acclimatization), mean CCT increased from 537 to 572 microm. Mean CCT in group 2
      increased from 534 to 563 microm (P = .048). The amount of decrease in SpO(2)
      paralleled the increase in CCT. There was no significant decrease in visual
      acuity. There was a significant correlation between CCT and cerebral acute
      mountain sickness score when controlled for SpO(2) and age. CONCLUSIONS: Corneal
      swelling during high-altitude climbs is promoted by low SpO(2). Systemic delivery
      of oxygen to the anterior chamber seems to play a greater role in corneal
      oxygenation than previously thought. Adhering to a slower ascent profile results
      in less corneal edema. Visual acuity in healthy corneas is not adversely affected
      by edema at altitudes of up to 6300 m. Individuals with more acute mountain
      sickness-related symptoms had thicker corneas, possibly due to their higher
      overall susceptibility to hypoxia.

PMID- 20142538
TI  - Fixed combination of latanoprost and timolol vs individual components for primary
      open-angle glaucoma or ocular hypertension: a randomized, double-masked study.
AB  - OBJECTIVE: To assess the efficacy and safety of fixed-combination latanoprost
      timolol (FCLT) vs latanoprost or timolol monotherapy. METHODS: This 12-week,
      randomized, double-masked, parallel-group study included patients with open-angle
      glaucoma or ocular hypertension treated with a beta-blocker and with baseline
      intraocular pressure (IOP) of 26 through 36 mm Hg. Following washout, eligible
      patients were randomized to once-daily FCLT in the evening, latanoprost in the
      evening, or timolol in the morning. MAIN OUTCOME MEASURES: Postbaseline IOP
      assessments at 8 am, 10 am, and 4 pm at weeks 2, 6, and 12; statistical
      superiority of FCLT for the 18 pairwise comparisons between FCLT and the 2
      monotherapies, using analysis of variance. RESULTS: All therapies resulted in
      significant IOP reductions from baseline. Pairwise comparisons favored FCLT at
      all time points. When the 18 comparisons were tested simultaneously, FCLT was
      statistically superior to latanoprost at 7 of 9 time points and at all 9 time
      points when compared with timolol. In addition, FCLT was associated with greater
      percentage reductions in diurnal IOP levels and a greater likelihood of achieving
      lower mean diurnal IOP levels. Diurnal IOP reductions of 30% or more from
      baseline to week 12 were achieved by 73.5%, 57.5%, and 32.8% of those treated
      with FCLT, latanoprost, and timolol, respectively (P = .007 for FCLT vs timolol;
      P < .001 for FCLT vs latanoprost). All therapies were well tolerated.
      CONCLUSIONS: Fixed-combination latanoprost-timolol therapy is as safe and
      effective in lowering IOP in patients with either ocular hypertension or glaucoma
      as monotherapy with latanoprost or timolol. Combination therapy can be used to
      treat patients for whom monotherapy does not provide sufficient IOP reduction.
      APPLICATION TO CLINICAL PRACTICE: The simplicity, efficacy, and tolerability of
      FCLT contribute to its utility in clinical practice. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier NCT00277498.

PMID- 20142541
TI  - Efficacy of sustained topical dorzolamide therapy for cystic macular lesions in
      patients with X-linked retinoschisis.
AB  - OBJECTIVE: To determine the efficacy of sustained topical therapy with
      dorzolamide hydrochloride, 2%, on visual acuity and cystic macular lesions in
      patients with juvenile X-linked retinoschisis (XLRS). DESIGN: Retrospective
      analysis. SETTING: University hospital, tertiary care referral center. PATIENTS:
      Twenty-nine eyes of 15 patients with XLRS receiving treatment with the topical
      dorzolamide formulation for 4 to 41 months were enrolled. MAIN OUTCOME MEASURES:
      Changes in visual acuity, cystic macular lesions, and central foveal zone
      thickness on optical coherence tomography during follow-up for the duration of
      treatment. RESULTS: Among the 15 patients with XLRS, 20 eyes (69%) of 11 patients
      showed a positive response to treatment. Five of the 20 eyes (25%) in 3 of the 11
      patients showed an initial response and a subsequent rebound of macular cysts. In
      4 eyes (14%) of 3 patients, there was no response to treatment, but the macular
      cysts did not worsen compared with the baseline level. In 5 additional eyes (17%)
      of 4 patients, there was no response to treatment, and the macular cysts worsened
      when compared with the baseline level. Sixteen eyes (55%) of 12 patients had
      improvement in best-corrected visual acuity by at least 7 letters in at least 1
      eye at the most recent follow-up visit. Seventeen eyes (59%) of 10 patients
      showed a reduction in the central foveal zone thickness in at least 1 eye when
      compared with the pretreatment level. CONCLUSION: Patients with XLRS have the
      potential to experience a beneficial effect from sustained treatment with
      dorzolamide, 2%.

PMID- 20142542
TI  - Dr Thompson's Eye Water.

PMID- 20142544
TI  - Impact of liver transplantation on transthyretin-related ocular amyloidosis in
      Japanese patients.
AB  - OBJECTIVE: To evaluate the long-term impact of liver transplantation on ocular
      manifestations of familial amyloid polyneuropathy (FAP) in Japanese patients.
      METHODS: Medical records were retrospectively reviewed in a long-term follow-up
      study. Of 52 patients with FAP amyloidogenic transthyretin Val30Met, 22 patients
      underwent liver transplantation. We assessed ocular manifestations, including
      amyloid deposition at the pupillary border, pupillary border with irregularity,
      vitreous opacities, and glaucoma, in patients who underwent liver
      transplantation. In addition, we compared the clinical characteristics of
      vitreous opacities-the most common ocular manifestation of FAP-in patients who
      underwent liver transplantation and those who did not to determine the effect of
      transplantation on the progression of ocular amyloidosis. RESULTS: Mean time
      after FAP onset was 10 years and after liver transplantation was 7 years in
      patients who underwent liver transplantation. All ocular manifestations increased
      with time after transplantation. Eight patients (36%) developed vitreous
      opacities and 4 patients (18%) developed glaucoma during follow-up. Mean time
      from FAP onset to vitreous opacities onset was significantly shorter in patients
      with early-onset disease who underwent liver transplantation than in those who
      did not. CONCLUSIONS: Patients with FAP who undergo liver transplantation
      continue to have a long-term risk of severe ocular manifestations, especially
      vitreous opacities and glaucoma, which can restrict their daily lives, even after
      liver transplantation.

PMID- 20142543
TI  - Relationship of blood pressure to retinal vessel diameter in type 1 diabetes
      mellitus.
AB  - OBJECTIVE: To examine the relationship of blood pressure (BP) and use of
      angiotensin-receptor blocker or angiotensin-converting enzyme inhibitor to
      retinal vessel diameter in normotensive, normoalbuminuric persons with type 1
      diabetes mellitus. METHODS: In a randomized, controlled clinical trial, clinic
      and 24-hour ambulatory BPs were measured in persons with type 1 diabetes mellitus
      and gradable fundus photographs both at baseline (n = 147) and at 5-year follow
      up (n = 124). Retinal arteriole and venule diameters were measured by a computer
      assisted technique. Individual arteriole and venule measurements were combined
      into summary indexes that reflect the average retinal arteriole (central retinal
      arteriole equivalent [CRAE]) and venule (central retinal venule equivalent
      [CRVE]) diameter of an eye, respectively. RESULTS: While controlling for age,
      study site, glycosylated hemoglobin level, and ambulatory pulse rate, the daytime
      ambulatory systolic (-0.29-microm effect per 1 mm Hg; P = .02), daytime
      ambulatory diastolic (-0.44-microm effect per 1 mm Hg; P = .04), nighttime
      ambulatory systolic (-0.27-microm effect per 1 mm Hg; P = .03), and 24-hour
      ambulatory systolic (-0.31-microm effect per 1 mm Hg; P = .03) BPs were cross
      sectionally associated with a smaller CRAE. While controlling for age, study
      site, glycosylated hemoglobin level, ambulatory pulse rate, and baseline CRAE, no
      BP measure was associated with a change in CRAE or CRVE during 5 years of follow
      up. Treatment with losartan potassium or enalapril maleate was not associated
      with a statistically significant change in CRAE or CRVE. CONCLUSION: Angiotensin
      converting enzyme inhibitor or angiotensin-receptor blocker therapy does not
      affect retinal arteriole or venule diameter in normotensive persons with type 1
      diabetes mellitus. Trial Registration clinicaltrials.gov Identifier: NCT00143949.

PMID- 20142546
TI  - Expression of vascular endothelial growth factor in retinoblastoma.
AB  - OBJECTIVES: To investigate the immunohistochemical expression of vascular
      endothelial growth factor (VEGF) and to determine its possible association with
      tumor differentiation status, optic nerve and/or choroidal invasion, anterior
      chamber invasion, vitreous seeding, and basophilic staining of the vascular
      walls. METHODS: A retrospective study was performed to identify the expression of
      VEGF in 47 of 129 consecutive patients with retinoblastoma treated at the Ocular
      Pathology Laboratory of the Anatomy and Pathology Institute of the Central
      University of Venezuela in Caracas from January 1, 2000, through December 31,
      2007. RESULTS: A positive correlation between VEGF staining intensity and time of
      progression and mitotic and apoptotic indexes was observed. However, no
      correlation was found between VEGF expression and other prognostic factors in
      this malignant neoplasm, including tumor stage as assessed by the Grabowski and
      Abramson classification. CONCLUSIONS: Although the isolated characterization of
      VEGF in retinoblastoma is not grounds for this protein to be considered a
      prognostic factor, its association with mitotic and apoptotic indexes suggests it
      may play a role in the progression of this disease. Thus, therapeutic targeting
      of VEGF in retinoblastoma may be an effective strategy to reduce tumor
      progression.

PMID- 20142547
TI  - Rate of endophthalmitis after cataract surgery in quebec, Canada, 1996-2005.
AB  - OBJECTIVE: To estimate the annual incidence of endophthalmitis after cataract
      surgery from January 1, 1996, through December 31, 2005, in Quebec, Canada.
      METHODS: Deidentified data were obtained from an outpatient physician billing
      database (Quebec State Control for Health Insurance [RAMQ]) with regard to all
      cataract surgical procedures performed from January 1, 1996, through December 31,
      2005, in Quebec. For this cohort, records of an International Classification of
      Diseases, Ninth Revision (ICD-9) code for endophthalmitis during the same years
      were requested from 2 sources: the RAMQ outpatient database and an inpatient
      hospital discharge database (Maintenance and Exploitation of Data for the Study
      of Hospitalized Patients [MED-ECHO]). Endophthalmitis after cataract surgery was
      assumed if it occurred within 90 days of the surgery. Risk factors were examined
      using chi(2) tests and logistic regression. RESULTS: After exclusions, 490 690
      cataract surgical procedures were performed from January 1, 1996, through
      December 31, 2005. A total of 754 cases of endophthalmitis occurred within 90
      days after surgery for an overall incidence rate of 1.5 per 1000 surgical
      procedures (95% confidence interval [CI], 1.4-1.7). Factors associated with
      endophthalmitis included age of 85 years or older (odds ratio [OR], 1.34; 95% CI,
      1.06-1.70), male sex (1.44; 1.24-1.66), later year of surgery (0.94; 0.92-0.97),
      and region of cataract surgery, because regions 6 (2.21; 1.91-2.55) and 9 (4.00;
      2.48-6.43) had higher rates compared with all other regions. CONCLUSION: Reasons
      that explain the apparent decrease in endophthalmitis, especially in 2005, should
      be explored and further research performed to understand why certain patients and
      regions have higher risks of endophthalmitis after cataract surgery.

PMID- 20142545
TI  - Development of choroidal neovascularization in rats with advanced intense cyclic
      light-induced retinal degeneration.
AB  - OBJECTIVES: To study the progressive changes of intense cyclic light-induced
      retinal degeneration and to determine whether it results in choroidal
      neovascularization (CNV). METHODS: Albino rats were exposed to 12 hours of 3000
      lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography,
      fluorescein and indocyanine green angiography, and optical coherence tomography
      were performed prior to euthanization. Light-exposed animals were euthanized
      after 1, 3, or 6 months for histopathological evaluation. Retinas were examined
      for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by
      immunofluorescence staining. RESULTS: Long-term intense cyclic light exposure
      resulted in retinal degeneration with loss of the outer segments of
      photoreceptors and approximately two-thirds of the outer nuclear layer as well as
      development of subretinal pigment epithelium neovascularization after 1 month.
      Almost the entire outer nuclear layer was absent with the presence of CNV, which
      penetrated the Bruch membrane and extended into the outer retina after 3 months.
      Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment
      epithelial fibrous metaplasia, and connective tissue bands containing blood
      vessels extending into the retina were observed after 6 months. All intense light
      exposed animals showed an increased presence of 4-hydroxy-2-nonenal and
      nitrotyrosine staining. Optical coherence tomographic and angiographic studies
      confirmed retinal thinning and leakiness of the newly formed blood vessels.
      CONCLUSIONS: Our results suggest that albino rats develop progressive stages of
      retinal degeneration and CNV after long-term intense cyclic light exposure,
      allowing the detailed study of the pathogenesis and treatment of age-related
      macular degeneration. CLINICAL RELEVANCE: The ability to study the progressive
      pathogenesis of age-related macular degeneration and CNV will provide detailed
      knowledge about the disease and aid in the development of target-specific
      therapy.

PMID- 20142548
TI  - Association between the use of glaucoma medications and mortality.
AB  - OBJECTIVE: To evaluate the relationship between glaucoma medication use and
      death. METHODS: This study uses longitudinal data from 2003 to 2007 on persons 40
      years and older with glaucoma or suspected glaucoma enrolled in a large managed
      care network. Cox regression analysis was performed to estimate the hazard of
      death associated with the use of various glaucoma medication classes and
      combinations thereof. Multivariable models were adjusted for demographic
      characteristics and comorbid medical conditions. RESULTS: Of 21 506 participants
      with glaucoma or suspected glaucoma, 237 (1.1%) died during the study period. The
      use of any class of glaucoma medication was associated with a 74% reduced hazard
      of death (adjusted hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.16
      0.40) compared with no glaucoma medication use. This association was observed for
      use of a single agent alone, such as a topical beta-antagonist (0.44; 0.24-0.83)
      or a prostaglandin analogue (0.31; 0.18-0.54), and for use of different
      combinations of drug classes. CONCLUSIONS: After adjustment for potential
      confounding variables, the use of glaucoma medications was associated with a
      reduced likelihood of death in this large sample of US adults with glaucoma.
      Future investigations should explore this association further because these
      findings may have important clinical implications.

PMID- 20142549
TI  - Harvesting fresh tumor tissue from enucleated eyes: the 2008 Jack S. Guyton
      lecture.
AB  - There is an increasing need to obtain fresh tumor tissue and normal tissue for
      genetic studies and research following enucleation of an eye for uveal melanoma,
      retinoblastoma, and other lesions. A concern about doing this is that the globe
      will often collapse and lead to difficulties with gross and histopathologic
      interpretation. The technique reported herein is based on the creation of an
      opening in the sclera using an 8-mm corneal trephine followed by removal of tumor
      tissue. This method provides adequate tissue, preserves the spherical
      configuration of the eye, and allows for excellent histopathologic sections.

PMID- 20142550
TI  - Intense cyclic light-induced retinal degeneration in rats.

PMID- 20142551
TI  - Moving toward information in the blink of an eye.

PMID- 20142552
TI  - Kindred with prominent corneal nerves associated with a mutation in codon 804 of
      RET on chromosome 10q11.

PMID- 20142553
TI  - Intravitreous ranibizumab (lucentis) for radiation maculopathy.

PMID- 20142554
TI  - Unusual adaptive optics findings in a patient with bilateral maculopathy.

PMID- 20142555
TI  - Topical treatment for capillary hemangioma of the eyelid using beta-blocker
      solution.

PMID- 20142556
TI  - Propranolol for isolated orbital infantile hemangioma.

PMID- 20142557
TI  - Ocular involvement by epstein-barr virus-positive diffuse large B-cell lymphoma
      of the elderly: a new disease entity in the world health organization
      classification.

PMID- 20142558
TI  - Severe retinal vascular infarction after photodynamic therapy with verteporfin
      using the standard protocol.

PMID- 20142560
TI  - Diabetic macular edema following panretinal photocoagulation.

PMID- 20142561
TI  - Vasopressin V1a receptor polymorphism and interval walking training effects in
      middle-aged and older people.
AB  - We assessed whether single nucleotide polymorphism rs1042615 of the vasopressin
      V1a receptor altered the indices of lifestyle-related diseases in middle-aged and
      older people (mean+/-SD: 64+/-7 years), and, if so, whether it also altered the
      effects of interval walking training (IWT). CC, CT, and TT carriers of rs1042615
      (42, 118, and 64 men, respectively; 113, 263, and 154 women, respectively)
      performed IWT. We included 5 sets of 3-minute fast walking at > or =70% peak
      aerobic capacity for walking and 3-minute slow walking at 40% peak aerobic
      capacity per day for > or =4 days per week for 5 months. Before IWT, the body
      mass index and diastolic blood pressure (DBP) for men were 25.1+/-0.3 kg/m(2)
      (mean+/-SE) and 84+/-1 mm Hg in TT, higher than the 23.6+/-0.4 kg/m(2) and 78+/-1
      mm Hg in CC, respectively (P<0.01), differences that disappeared after IWT
      despite similar training achievement between groups (P>0.6). After IWT, body mass
      index and DBP decreased in TT (-0.9+/-0.1 kg/m(2) and -5+/-1 mm Hg,
      respectively), more than in CC (-0.5+/-0.1 kg/m(2) and 1+/-1 mm Hg, respectively;
      P<0.05), with a greater decrease in low-density lipoprotein cholesterol in TT
      than CC carriers (P<0.01). The decreases in DBP and low-density lipoprotein
      cholesterol were still greater in TT carriers even after adjustment for their
      pretraining values. On the other hand, for women, these parameters before IWT and
      their changes after IWT were similar among CC, CT, and TT carriers. Thus,
      polymorphism rs1042615 of the V1a receptor altered body mass index and DBP in
      middle-aged and older men and the training-induced responses of DBP and low
      density lipoprotein cholesterol, whereas women did not show any of these
      responses.

PMID- 20142562
TI  - Brain perivascular macrophages and central sympathetic activation after
      myocardial infarction: heart and brain interaction.

PMID- 20142563
TI  - Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive
      enhancer binding protein/vascular endothelial growth factor C expression and
      induces salt-sensitive hypertension in rats.
AB  - We showed recently that mononuclear phagocyte system (MPS) cells provide a
      buffering mechanism for salt-sensitive hypertension by driving interstitial
      lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing
      endothelial NO synthase protein expression in response to very high dietary salt
      via a tonicity-responsive enhancer binding protein/vascular endothelial growth
      factor C regulatory mechanism. We now tested whether isotonic saline and
      deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory
      response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received
      tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0%
      saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we
      further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to
      Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding
      protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial
      lymph capillaries, and increased endothelial NO synthase protein expression in
      skin interstitium. Clodronate liposome MPS cell depletion blocked MPS
      infiltration in the skin interstitium, resulting in unchanged tonicity-responsive
      enhance binding protein/vascular endothelial growth factor C levels and absent
      hyperplasia of the lymph capillary network. Moreover, no increased skin
      endothelial NO synthase protein expression occurred in either clodronate liposome
      treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response
      converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD
      rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated.
      We conclude that MPS cells act as onsite controllers of interstitial volume and
      blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity
      responsive enhancer binding protein/vascular endothelial growth factor C-mediated
      mechanism in the skin to maintain normal blood pressure in states of interstitial
      Na(+) and Cl(-) accumulation. Failure of this physiological extrarenal regulatory
      mechanism leads to a salt-sensitive blood pressure response.

PMID- 20142564
TI  - Brain perivascular macrophages and the sympathetic response to inflammation in
      rats after myocardial infarction.
AB  - Inflammation is associated with increased sympathetic drive in cardiovascular
      diseases. Blood-borne proinflammatory cytokines, markers of inflammation, induce
      cyclooxygenase 2 (COX-2) activity in perivascular macrophages of the blood-brain
      barrier. COX-2 generates prostaglandin E(2), which may enter the brain and
      increase sympathetic nerve activity. We examined the contribution of this
      mechanism to augmented sympathetic drive in rats after myocardial infarction
      (MI). Approximately 24 hours after acute MI, rats received an
      intracerebroventricular injection (1 microL/min over 40 minutes) of clodronate
      liposomes (MI+CLOD) to eliminate brain perivascular macrophages, liposomes alone,
      or artificial cerebrospinal fluid. A week later, COX-2 immunoreactivity in
      perivascular macrophages and COX-2 mRNA and protein had increased in hypothalamic
      paraventricular nucleus of MI rats treated with artificial cerebrospinal fluid or
      liposomes alone compared with sham-operated rats. In MI+CLOD rats, neither
      perivascular macrophages nor COX-2 immunoreactivity was seen in the
      paraventricular nucleus, and COX-2 mRNA and protein levels were similar to those
      in sham-operated rats. Prostaglandin E(2) in cerebrospinal fluid, paraventricular
      nucleus neuronal excitation, and plasma norepinephrine were less in MI+CLOD rats
      than in MI rats treated with artificial cerebrospinal fluid or liposomes alone
      but more than in sham-operated rats. Intracerebroventricular CLOD had no effect
      on interleukin 1beta and tumor necrosis factor-alpha mRNA and protein in the
      paraventricular nucleus or plasma interleukin-1beta and tumor necrosis factor
      alpha, which were increased in MI compared with sham-operated rats. In normal
      rats, pretreatment with intracerebroventricular CLOD reduced (P<0.05) the renal
      sympathetic, blood pressure, and heart rate responses to intracarotid artery
      injection of tumor necrosis factor-alpha (0.5 microg/kg); intracerebroventricular
      liposomes had no effect. The results suggest that proinflammatory cytokines
      stimulate sympathetic excitation after MI by inducing COX-2 activity and
      prostaglandin E(2) production in perivascular macrophages of the blood-brain
      barrier.

PMID- 20142565
TI  - Angiotensin receptor blocker protection against podocyte-induced sclerosis is
      podocyte angiotensin II type 1 receptor-independent.
AB  - In the present study, we tested the hypothesis that the renoprotective effect of
      an angiotensin receptor blocker depends on the angiotensin II type 1 (AT(1))
      receptor on podocytes. For this purpose, we generated podocyte-specific knockout
      mice for the AT(1) gene (Agtr1a) and crossed with NEP25, in which selective
      podocyte injury can be induced by immunotoxin, anti-Tac(Fv)-PE38. Four weeks
      after the addition of anti-Tac(Fv)-PE38, urinary albumin:creatinine ratio was not
      attenuated in Agtr1a knockout/NEP25 mice (n=18) compared with that in control
      NEP25 mice (n=13; 8.08+/-2.41 in knockout versus 4.84+/-0.73 in control). Both
      strains of mice showed similar degrees of sclerosis (0.66+/-0.17 versus 0.82+/
      0.27 on a 0 to 4 scale) and downregulation of nephrin (5.78+/-0.45 versus 5.65+/
      0.58 on a 0 to 8 scale). In contrast, AT(1) antagonist or an angiotensin I
      converting enzyme inhibitor, but not hydralazine, remarkably attenuated
      proteinuria and sclerosis in NEP25 mice. Moreover, continuous angiotensin II
      infusion induced microalbuminuria similarly in both Agtr1a knockout and wild-type
      mice. Thus, angiotensin inhibition can protect podocytes and prevent the
      development of glomerulosclerosis independent of podocyte AT(1). Possible
      mechanisms include inhibitory effects on AT(1) of other cells or through
      mechanisms independent of AT(1). Our study further demonstrates that measures
      that directly affect only nonpodocyte cells can have beneficial effects even when
      sclerosis is triggered by podocyte-specific injury.

PMID- 20142566
TI  - Providing patients with global cardiovascular risk information: is knowledge
      power?

PMID- 20142567
TI  - The effect of giving global coronary risk information to adults: a systematic
      review.
AB  - BACKGROUND: Global coronary heart disease (CHD) risk estimation (ie, a
      quantitative estimate of a patient's chances of CHD calculated by combining risk
      factors in an empirical equation) is recommended as a starting point for primary
      prevention efforts in all US adults. Whether it improves outcomes is currently
      unknown. METHODS: To assess the effect of providing global CHD risk information
      to adults, we performed a systematic evidence review. We searched MEDLINE for the
      years 1980 to 2008, Psych Info, CINAHL, and the Cochrane Database and included
      English-language articles that met prespecified inclusion criteria. Two reviewers
      independently reviewed titles, abstracts, and articles for inclusion and assessed
      study quality. RESULTS: We identified 20 articles, reporting on 18 unique fair or
      good quality studies (including 14 randomized controlled studies). These showed
      that global CHD risk information alone or with accompanying education increased
      the accuracy of perceived risk and probably increased intent to start therapy.
      Studies with repeated risk information or risk information and repeated doses of
      counseling showed small significant reductions in predicted CHD risk (absolute
      differences, -0.2% to -2% over 10 years in studies using risk estimates derived
      from Framingham equations). Studies providing global risk information at only 1
      point in time seemed ineffective. CONCLUSIONS: Global CHD risk information seems
      to improve the accuracy of risk perception and may increase intent to initiate
      CHD prevention among individuals at moderate to high risk. The effect of global
      risk presentation on more distal outcomes is less clear and seems to be related
      to the intensity of accompanying interventions.

PMID- 20142568
TI  - Standard care impact on effects of highly active antiretroviral therapy adherence
      interventions: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Poor adherence to medication limits the effectiveness of treatment
      for human immunodeficiency virus. Systematic reviews can identify practical and
      effective interventions. Meta-analyses that control for variability in standard
      care provided to control groups may produce more accurate estimates of
      intervention effects. METHODS: To examine whether viral load and adherence
      success rates could be accurately explained by the active content of highly
      active antiretroviral therapy (HAART) adherence interventions when controlling
      for variability in care delivered to controls, databases were searched for
      randomized controlled trials of HAART adherence interventions published from 1996
      to January 2009. A total of 1342 records were retrieved, and 52 articles were
      examined in detail. Directly observed therapy and interventions targeting
      specific patient groups (ie, psychiatric or addicted patients, patients <18
      years) were excluded, yielding a final sample of 31 trials. Two coders
      independently retrieved study details. Authors were contacted to complete missing
      data. RESULTS: Twenty studies were included in the analyses. The content of
      adherence care provided to control and intervention groups predicted viral load
      and adherence success rates in both conditions (P < .001 for all comparisons),
      with an estimated impact of optimal adherence care of 55 percentage points. After
      controlling for variability in care provided to controls, the capacity of the
      interventions accurately predicted viral load and adherence effect sizes (R(2) =
      0.78, P = .02; R(2) = 0.28, P < .01). Although interventions were generally
      beneficial, their effectiveness reduced noticeably with increasing levels of
      standard care. CONCLUSIONS: Intervention and control patients were exposed to
      effective adherence care. Future meta-analyses of (behavior change) interventions
      should control for variability in care delivered to active controls. Clinical
      practice may be best served by implementing current best practice.

PMID- 20142569
TI  - The course of nonspecific chest pain in primary care: symptom persistence and
      health care usage.
AB  - BACKGROUND: Nonspecific chest pain is common in primary care, yet knowledge is
      sparse about its course and outcome and how they relate to optimum health care
      usage. We investigated the following observations: (1) many patients who present
      with nonspecific chest pain in primary care show symptom persistence for 6
      months, (2) many patients with nonspecific chest pain showed signs of
      overinvestigation, and (3) many patients with chronic chest pain were referred to
      mental health specialists. METHODS: We conducted a prospective, general physician
      based cohort study with 6-week and 6-month follow-ups in 74 primary care offices
      in Hessen, Germany. Of approximately 190 000 consecutive patients who visited
      their general physicians from October 1, 2005, to July 31, 2006, 807 patients
      with nonspecific chest pain were identified by an expert committee (delayed-type
      reference standard). The dropout rate was 2.7%. Main outcome measures were
      persistent chest pain at a 6-month follow-up visit and health care usage at 6
      months. RESULTS: The rate of persistent chest pain was 55.5%. A total of 10.7% of
      patients had inappropriate health care usage, defined as 2 or more visits to a
      cardiologist or 3 or more cardiac diagnostic investigations. Most patients with
      persistent nonspecific chest pain were referred to a cardiologist, and less than
      2% were referred to mental health specialists. CONCLUSIONS: For most patients
      with nonspecific chest pain, standard medical care does not offer sufficient help
      for symptom relief. One-tenth of patients with persistent chest pain underwent
      additional diagnostic testing of no known clinical benefit. Psychological
      referrals were rarely given.

PMID- 20142570
TI  - Acute selenium toxicity associated with a dietary supplement.
AB  - BACKGROUND: Selenium is an element necessary for normal cellular function, but it
      can have toxic effects at high doses. We investigated an outbreak of acute
      selenium poisoning. METHODS: A case was defined as the onset of symptoms of
      selenium toxicity in a person within 2 weeks after ingesting a dietary supplement
      manufactured by "Company A," purchased after January 1, 2008. We conducted case
      finding, administered initial and 90-day follow-up questionnaires to affected
      persons, and obtained laboratory data where available. RESULTS: The source of the
      outbreak was identified as a liquid dietary supplement that contained 200 times
      the labeled concentration of selenium. Of 201 cases identified in 10 states, 1
      person was hospitalized. The median estimated dose of selenium consumed was 41
      749 microg/d (recommended dietary allowance is 55 microg/d). Frequently reported
      symptoms included diarrhea (78%), fatigue (75%), hair loss (72%), joint pain
      (70%), nail discoloration or brittleness (61%), and nausea (58%). Symptoms
      persisting 90 days or longer included fingernail discoloration and loss (52%),
      fatigue (35%), and hair loss (29%). The mean initial serum selenium concentration
      of 8 patients was 751 microg/L (reference range, < or =125 microg/L). The mean
      initial urine selenium concentration of 7 patients was 166 microg/24 h (reference
      range, < or =55 microg/24 h). CONCLUSIONS: Toxic concentrations of selenium in a
      liquid dietary supplement resulted in a widespread outbreak. Had the
      manufacturers been held to standards used in the pharmaceutical industry, it may
      have been prevented.

PMID- 20142571
TI  - The dietary supplement health and education act: time for a reassessment: comment
      on "acute selenium toxicity associated with a dietary supplement".

PMID- 20142572
TI  - Failure of automated telephone outreach with speech recognition to improve
      colorectal cancer screening: a randomized controlled trial.
AB  - BACKGROUND: Automated telephone outreach with speech recognition (ATO-SR) is used
      extensively by health plans. Whether ATO-SR can increase rates of colorectal
      cancer (CRC) screening is unknown. METHODS: We randomly allocated 40 000 health
      plan members to ATO-SR and 40 000 to usual care, of whom 10 432 and 10 506 in the
      intervention and usual care groups, respectively, had not been previously
      screened and were therefore eligible for analysis. The intervention was a single
      interactive outreach call using speech recognition to engage participants in
      conversation about the importance of CRC screening and options for and barriers
      to screening. The intervention directed participants to contact their primary
      care provider to schedule screening. The primary end point was any CRC screening
      in the year following intervention. Colonoscopy in the year following
      intervention was a secondary outcome. RESULTS: The incidence of any CRC screening
      was 30.6% in the intervention group and 30.4% in the usual care group (P = .76).
      After adjustment for available covariates, there remained no intervention effect
      (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.94-1.07). A
      total of 21.4% of members in the intervention group and 20.3% in the usual care
      group underwent colonoscopy (P = .04). In multivariate analysis, there was a
      small intervention effect on colonoscopy (OR, 1.08; 95% CI, 1.00-1.16).
      CONCLUSIONS: This study showed that ATO-SR failed to improve rates of CRC
      screening. Future studies should examine approaches that combine efforts to
      target patients and their health care providers to overcome the barriers to CRC
      screening. Trial Registration clinicaltrials.gov Identifier: NCT00792285.

PMID- 20142573
TI  - Low back pain and best practice care: A survey of general practice physicians.
AB  - BACKGROUND: Acute low back pain (LBP) is primarily managed in general practice.
      We aimed to describe the usual care provided by general practitioners (GPs) and
      to compare this with recommendations of best practice in international evidence
      based guidelines for the management of acute LBP. METHODS: Care provided in 3533
      patient visits to GPs for a new episode of LBP was mapped to key recommendations
      in treatment guidelines. The proportion of patient encounters in which care
      arranged by a GP aligned with these key recommendations was determined for the
      period 2005 through 2008 and separately for the period before the release of the
      local guideline in 2004 (2001-2004). RESULTS: Although guidelines discourage the
      use of imaging, over one-quarter of patients were referred for imaging.
      Guidelines recommend that initial care should focus on advice and simple
      analgesics, yet only 20.5% and 17.7% of patients received these treatments,
      respectively. Instead, the analgesics provided were typically nonsteroidal anti
      inflammatory drugs (37.4%) and opioids (19.6%). This pattern of care was the same
      in the periods before and after the release of the local guideline. CONCLUSIONS:
      The usual care provided by GPs for LBP does not match the care endorsed in
      international evidence-based guidelines and may not provide the best outcomes for
      patients. This situation has not improved over time. The unendorsed care may
      contribute to the high costs of managing LBP, and some aspects of the care
      provided carry a higher risk of adverse effects.

PMID- 20142574
TI  - Adherence, not just for patients: comment on "low back pain and best practice
      care".

PMID- 20142575
TI  - Impact of health disparities collaboratives on racial/ethnic and insurance
      disparities in US community health centers.
AB  - BACKGROUND: The Health Resources and Services Administration Health Disparities
      Collaboratives (HDCs) were developed to improve care for chronic medical
      conditions in community health centers (CHCs). METHODS: We examined whether HDCs
      reduced disparities in quality by race/ethnicity or insurance status in CHCs
      nationally. We performed a controlled preintervention/postintervention study of
      44 CHCs participating in HDCs for asthma, diabetes mellitus, or hypertension and
      20 "external" control CHCs that had not participated. Each intervention center
      also served as an "internal" control for another condition. For each condition,
      we created an overall quality score, defined disparities in care as the
      differences in care between racial/ethnic groups and insurance groups, and
      examined changes in disparity through a series of hierarchical models using a 3
      way interaction term among period, patient characteristics of interest, and
      treatment group. RESULTS: Overall, HDCs had little effect on disparities in
      composite measures for asthma, diabetes, and hypertension. For asthma care,
      collaborative centers had a baseline Hispanic-white disparity of 6.5%, which
      changed to a higher quality of recommended care for Hispanic patients over white
      patients by 0.8%, resulting in a significantly reduced Hispanic-white disparity
      compared with the change in disparity seen in external controls (P = .04). There
      were no other improvements in racial/ethnic or insurance disparities for any
      other conditions. CONCLUSIONS: Although HDCs are known to improve quality of care
      in CHCs, they had minimal effect on racial/ethnic and insurance disparities. In
      addition to targeting improvement in overall quality, future initiatives should
      include activities aimed at disparity reduction as an outcome.

PMID- 20142576
TI  - Passive smoking and tuberculosis.
AB  - BACKGROUND: Increasing evidence has incriminated active smoking as a causal
      factor for tuberculosis (TB). However, the effect of secondhand tobacco smoke
      exposure on TB has not been similarly elucidated. METHODS: A cohort of 15 486
      female never-smokers aged 65 to 74 years and living with their surviving husband
      were enrolled at 18 Elderly Health Centers in Hong Kong from 2000 to 2003 and
      followed up prospectively through linkage with the territory-wide TB notification
      registry and death registry for TB and death until December 31, 2008, using an
      identity card number as a unique identifier. The relationship between passive
      smoking and the development of TB was assessed with adjustment for other baseline
      characteristics. RESULTS: Passive exposure to secondhand tobacco smoke in the
      household was independently associated with obstructive lung disease (odds [OR],
      1.43; 95% confidence interval [CI], 1.16-1.77) and diabetes mellitus (OR, 1.13;
      95% CI, 1.02-1.26) at baseline and with the development of both active TB (hazard
      ratio [HR], 1.49; 95% CI, 1.01-2.19) and culture-confirmed TB (HR, 1.70; 95% CI,
      1.04-2.80) on prospective follow-up after potentially confounding background
      variables were controlled for. Passive smoking accounted for 13.7% of active TB
      and for 18.5% of culture-positive TB in this cohort. CONCLUSIONS: Similar to
      active smoking, passive exposure to secondhand tobacco smoke in the household
      also predisposes to the development of TB. Increased emphasis should therefore be
      put on tobacco control in national TB programs.

PMID- 20142577
TI  - Secondhand smoke and infectious disease in adults: A global women's health
      concern: Comment on "Passive Smoking and Tuberculosis".

PMID- 20142578
TI  - Impact of hospital-associated hyponatremia on selected outcomes.
AB  - BACKGROUND: Hyponatremia is the most common electrolyte disorder encountered in
      hospitalized patients. METHODS: We evaluated whether hospital-associated
      hyponatremia has an independent effect on all-cause mortality, hospital length of
      stay (LOS), and patient disposition. This cohort study included all adult
      hospitalizations at an academic medical center occurring between 2000-2007 for
      which an admission serum sodium concentration ([Na(+)]) was available (N = 53
      236). We examined community-acquired hyponatremia (admission serum [Na(+)], <138
      mEq/L [to convert to millimoles per liter, multiply by 1.0]), hospital-aggravated
      hyponatremia (community-acquired hyponatremia complicated by worsening in serum
      [Na(+)]), and hospital-acquired hyponatremia (nadir serum [Na(+)], <138 mEq/L
      with a normal admission serum [Na(+)]). The independent associations of these
      hyponatremic presentations with in-hospital mortality, LOS, and patient
      disposition were evaluated using generalized estimating equations adjusted for
      age, sex, race, admission service, and Deyo-Charlson Comorbidity Index score.
      RESULTS: Community-acquired hyponatremia occurred in 37.9% of hospitalizations
      and was associated with adjusted odds ratios (ORs) of 1.52 (95% confidence
      interval [CI], 1.36-1.69) for in-hospital mortality and 1.12 (95% CI, 1.08-1.17)
      for discharge to a short- or long-term care facility and a 14% (95% CI, 11%-16%)
      adjusted increase in LOS. Hospital-acquired hyponatremia developed in 38.2% of
      hospitalizations longer than 1 day in which initial serum [Na(+)] was 138 to 142
      mEq/L. Hospital-acquired hyponatremia was associated with adjusted ORs of 1.66
      (95% CI, 1.39-1.98) for in-hospital mortality and 1.64 (95% CI, 1.55-1.74) for
      discharge to a facility and a 64% (95% CI, 60%-68%) adjusted increase in LOS. The
      strength of these associations tended to increase with hyponatremia severity.
      CONCLUSIONS: Hospital-associated hyponatremia is a common occurrence. All forms
      of hyponatremia are independently associated with in-hospital mortality and
      heightened resource consumption.

PMID- 20142579
TI  - Ventricular tachycardia after ingestion of ayurveda herbal antidiarrheal
      medication containing aconitum.
AB  - Ayurveda is an East Indian tradition involving the treatment of medical ailments
      through the use of herbal medications. A previously asymptomatic 62-year-old man
      with a history of hypertension and stable coronary artery disease developed
      paresthesias and fascicular and ventricular tachycardia after ingestion of an
      Ayurveda bowel regimen containing substrates from the Aconitum species, which is
      a known neurotoxin and cardiotoxin. Findings of electrophysiologic study and
      cardiac magnetic resonance imaging were within normal limits, pointing to the
      ingestion of Aconitum as the most likely source of his arrhythmia.

PMID- 20142580
TI  - Procedure training--is it time for a change?

PMID- 20142581
TI  - The evidence chasm.

PMID- 20142582
TI  - The need for more accurate terminology in discussing end-of-life options.

PMID- 20142583
TI  - Efficacy vs effectiveness in prostate-specific antigen screening.

PMID- 20142584
TI  - Prostate-specific antigen screening in the United States vs in the European
      Randomized Study of Screening for Prostate Cancer-Rotterdam.
AB  - Dissemination of prostate-specific antigen (PSA) testing in the United States
      coincided with an increasing incidence of prostate cancer, a shift to earlier
      stage disease at diagnosis, and decreasing prostate cancer mortality. We compared
      PSA screening performance with respect to prostate cancer detection in the US
      population vs in the Rotterdam section of the European Randomized Study of
      Screening for Prostate Cancer (ERSPC-Rotterdam). We developed a simulation model
      for prostate cancer and PSA screening for ERSPC-Rotterdam. This model was then
      adapted to the US population by replacing demography parameters with US-specific
      ones and the screening protocol with the frequency of PSA tests in the US
      population. We assumed that the natural progression of prostate cancer and the
      sensitivity of a PSA test followed by a biopsy were the same in the United States
      as in ERSPC-Rotterdam. The predicted prostate cancer incidence peak in the United
      States was then substantially higher than the observed prostate cancer incidence
      peak (13.3 vs 8.1 cases per 1000 man-years). However, the actual observed
      incidence was reproduced by assuming a substantially lower PSA test sensitivity
      in the United States than in ERSPC-Rotterdam. For example, for nonpalpable local-
      or regional-stage cancers (ie, stage T1M0), the estimates of PSA test sensitivity
      were 0.26 in the United States vs 0.94 in ERSPC-Rotterdam. We conclude that the
      efficacy of PSA screening in detecting prostate cancer was lower in the United
      States than in ERSPC-Rotterdam.

PMID- 20142585
TI  - Cardiotoxicity after childhood cancer: beginning with the end in mind.

PMID- 20142586
TI  - Phase II trial of weekly bortezomib in combination with rituximab in relapsed or
      relapsed and refractory Waldenstrom macroglobulinemia.
AB  - PURPOSE: This study aimed to determine activity and safety of weekly bortezomib
      and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia
      (WM). PATIENTS AND METHODS: Patients who had at least one previous therapy were
      eligible. All patients received bortezomib intravenously weekly at 1.6 mg/m(2) on
      days 1, 8, and 15, every 28 days for six cycles and rituximab 375 mg/m(2) weekly
      on cycles 1 and 4. The primary end point was the percentage of patients with at
      least a minor response. RESULTS: Thirty-seven patients were treated. The majority
      of patients (78%) completed treatment per protocol. At least minimal response
      (MR) or better was observed in 81% (95% CI, 65% to 92%), with two patients (5%)
      in complete remission (CR)/near CR, 17 patients (46%) in partial response, and 11
      patients (30%) in MR. The median time to progression was 16.4 months (95% CI,
      11.4 to 21.1 months). Death occurred in one patient due to viral pneumonia. The
      most common grade 3 and 4 therapy-related adverse events included reversible
      neutropenia in 16%, anemia in 11%, and thrombocytopenia in 14%. Grade 3
      peripheral neuropathy occurred in only two patients (5%). The median progression
      free (PFS) is 15.6 months (95% CI, 11 to 21 months), with estimated 12-month and
      18-month PFS of 57% (95% CI, 39% to 75%) and 45% (95% CI, 27% to 63%),
      respectively. The median overall survival has not been reached. CONCLUSION: The
      combination of weekly bortezomib and rituximab showed significant activity and
      minimal neurologic toxicity in patients with relapsed WM.

PMID- 20142587
TI  - Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients
      with advanced ErbB2-positive breast cancer.
AB  - PURPOSE: Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase
      inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of
      patients with advanced ErbB2-positive breast cancer-those with and those without
      prior trastuzumab treatment-in an open-label, multicenter, phase II trial.
      PATIENTS AND METHODS: Patients in the two cohorts (prior trastuzumab, n = 66; no
      prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary
      end point was the 16-week progression-free survival (PFS) rate for the evaluable
      population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed
      by independent review. RESULTS: The 16-week PFS rates were 59% for patients with
      prior trastuzumab treatment and 78% for patients with no prior trastuzumab
      treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response
      rates were 24% among patients with prior trastuzumab treatment and 56% in the
      trastuzumab-naive cohort. The most common adverse events were diarrhea, nausea,
      vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse
      event, occurring in 30% of patients with prior trastuzumab treatment and in 13%
      of patients with no prior trastuzumab treatment, which prompted dose reductions
      in 29% and 4% of patients, respectively, but treatment discontinuation in only
      one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported.
      CONCLUSION: Oral neratinib showed substantial clinical activity and was
      reasonably well tolerated among both heavily pretreated and trastuzumab-naive
      patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most
      common adverse effect but was manageable with antidiarrheal agents and dose
      modification.

PMID- 20142588
TI  - Consistency in insurance coverage for iatrogenic conditions resulting from cancer
      treatment including fertility preservation.

PMID- 20142589
TI  - Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights
      platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as
      potential therapeutic targets.
AB  - PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating
      of pediatric malignancies and one for which no effective therapy exists. A major
      contributor to the failure of therapeutic trials is the assumption that biologic
      properties of brainstem tumors in children are identical to cerebral high-grade
      gliomas of adults. A better understanding of the biology of DIPG itself is needed
      in order to develop agents targeted more specifically to these children's
      disease. Herein, we address this lack of knowledge by performing the first high
      resolution single nucleotide polymorphism (SNP) -based DNA microarray analysis of
      a series of DIPGs. PATIENTS AND METHODS: Eleven samples (nine postmortem and two
      pretreatment surgical samples), the largest series thus far examined, were
      hybridized to SNP arrays (250 k or 6.0). The study was approved by the research
      ethics board at our institution. All array findings were validated using
      quantitative polymerase chain reaction, fluorescence in situ hybridization,
      immunohistochemistry, and/or microsatellite analysis. RESULTS: Analysis of DIPG
      copy number alterations showed recurrent changes distinct from those of pediatric
      supratentorial high-grade astrocytomas. Thirty-six percent of DIPGs had gains in
      platelet-derived growth factor receptor alpha (PDGFRA; 4 to 18 copies) and all
      showed PDGFR-alpha expression. Low-level gains in poly (ADP-ribose) polymerase
      (PARP) -1 were identified in three cases. Pathway analysis revealed genes with
      loss of heterozygosity were enriched for DNA repair pathways. CONCLUSION: To our
      knowledge, our data provides the first, comprehensive high-resolution genomic
      analysis of pediatric DIPG. Our findings of recurrent involvement of the PDGFR
      pathway as well as defects in DNA repair pathways coupled with gain of PARP-1
      highlight two potential, biologically based, therapeutic targets directed
      specifically at this devastating disease.

PMID- 20142590
TI  - Sustained molecular response with interferon alfa maintenance after induction
      therapy with imatinib plus interferon alfa in patients with chronic myeloid
      leukemia.
AB  - PURPOSE: Imatinib induces sustained remissions in patients with chronic
      myelogenous leukemia (CML), but fails to eradicate CML stem cells. This is of
      major concern regarding the issues of cure, long-term imatinib tolerability, and
      imatinib resistance. We therefore asked whether interferon alfa-2a (IFN) alone
      could maintain molecular remissions achieved by a prior combination therapy with
      imatinib and IFN. PATIENTS AND METHODS: Imatinib therapy was stopped in 20
      patients who had concomitantly been pretreated with imatinib and IFN for a median
      of 2.4 years (range, 0.2 to 4.8 years) and 2.5 years (range, 0.2 to 4.9 years),
      respectively. After imatinib discontinuation, remission status was monitored
      monthly by quantitative analysis of the peripheral-blood BCR-ABL mRNA levels
      using real-time polymerase chain reaction. Proteinase-3 expression and proteinase
      3-specific cytotoxic T cells (CTLs) were longitudinally measured to assess
      putative markers of IFN response. RESULTS: With a median time of 2.4 years after
      imatinib withdrawal (range, 0.5 to 4.0 years), 15 (75%) of 20 patients remained
      in remission. The number of patients in complete molecular remission increased
      under IFN from two patients at baseline to five patients after 2 years. Relapses
      occurred in five patients within 0.4 years (range, 0.2 to 0.8 years), but
      patients underwent rescue treatment with imatinib, re-establishing molecular
      remission. IFN therapy was associated with an increase in the expression of
      leukemia-associated antigen proteinase 3 and induction of proteinase-3-specific
      CTLs. CONCLUSION: Treatment with IFN enables discontinuation of imatinib in most
      patients after prior imatinib/IFN combination therapy and may result in improved
      molecular response. Induction of a proteinase-3-specific CTL response by IFN may
      contribute to this effect.

PMID- 20142591
TI  - Cost effectiveness of positron emission tomography in patients with Hodgkin's
      lymphoma in unconfirmed complete remission or partial remission after first-line
      therapy.
AB  - PURPOSE: To assess the cost effectiveness of fluorine-18-fluorodeoxyglucose
      positron emission tomography (FDG-PET) in patients with Hodgkin's lymphoma (HL)
      with unconfirmed complete remission (CRu) or partial remission (PR) after first
      line treatment. PATIENTS AND METHODS: One hundred thirty patients with HL were
      prospectively studied. After treatment, all patients with CRu/PR were evaluated
      with FDG-PET. In addition, PET-negative patients were evaluated with standard
      follow-up, and PET-positive patients were evaluated with biopsies of the positive
      lesions. Local unit costs of procedures and tests were evaluated. Cost
      effectiveness was determined by evaluating projected annual economic impact of
      strategies without and with FDG-PET on HL management. RESULTS: After treatment,
      CRu/PR was observed in 50 (40.0%) of the 127 patients; the sensitivity,
      specificity, and positive and negative predictive values of FDG-PET were 100%,
      92.0%, 92.3%, and 100%, respectively (accuracy of 95.9%). Local restaging costs
      without PET were $350,050 compared with $283,262 with PET, a 19% decrease. The
      incremental cost-effectiveness ratio is -$3,268 to detect one true case. PET
      costs represented 1% of total costs of HL treatment. Simulated costs in the 974
      patients registered in the 2008 Brazilian public health care database showed that
      the strategy including restaging PET would have a total program cost of
      $56,498,314, which is $516,942 less than without restaging PET, resulting in a 1%
      cost saving. CONCLUSION: FDG-PET demonstrated 95.9% accuracy in restaging for
      patients with HL with CRu/PR after first-line therapy. Given the observed
      probabilities, FDG-PET is highly cost effective and would reduce costs for the
      public health care program in Brazil.

PMID- 20142592
TI  - Phase I/II study of the Src inhibitor dasatinib in combination with erlotinib in
      advanced non-small-cell lung cancer.
AB  - PURPOSE: Src family kinase (SFK) proteins are frequently activated in cancer and
      can coordinate tumor cell growth, survival, invasion, and angiogenesis. Given the
      importance of SFK signaling in cancer, known cooperation between SFK and
      epidermal growth factor receptor (EGFR) signaling, and efficacy of EGFR
      inhibitors, we performed a phase I trial combining dasatinib, an SFK and
      multikinase inhibitor, with erlotinib, an EGFR inhibitor, in patients with
      advanced non-small-cell lung cancer. PATIENTS AND METHODS: Patients received
      erlotinib for 1 week before addition of dasatinib; pharmacokinetics were
      performed after weeks 1 and 2. Four cohorts were examined, including twice-daily
      and daily dasatinib dosing. Responses were assessed after 8 weeks. Plasma levels
      of angiogenic markers (vascular endothelial growth factor [VEGF], interleukin-8,
      and basic fibroblast growth factor [bFGF]) were determined before and during
      treatment. RESULTS: Thirty-four patients were enrolled. The average duration of
      treatment was 73 days. The main adverse events include GI (diarrhea, anorexia,
      and nausea), skin rash, cytopenias, pleural effusions, and fatigue. No effect of
      escalating doses of dasatinib was observed on erlotinib pharmacokinetics. Two
      partial responses and one bone response were observed, and the disease control
      rate was 63%. Reductions in plasma VEGF and bFGF were observed, and reductions in
      VEGF correlated with disease control. CONCLUSION: The combination of erlotinib
      and dasatinib is tolerable, with adverse effects consistent with the two agents.
      Disease control and inhibition of plasma angiogenesis markers were observed.
      Personalized strategies for deployment of SFK should receive further attention.

PMID- 20142593
TI  - Phase II study of sunitinib in patients with metastatic urothelial cancer.
AB  - PURPOSE: No standard therapy exists for metastatic urothelial cancer (UC) that
      has progressed after initial chemotherapy. This trial was designed to assess the
      efficacy and tolerability of sunitinib in patients with advanced, previously
      treated UC. PATIENTS AND METHODS: In this phase II trial, 77 patients received
      sunitinib between September 2006 and January 2009 on one of two schedules (50 mg
      per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously
      [cohort B]), using a Simon 2 stage design in each cohort separately. RESULTS: A
      partial response was seen in three of 45 patients (95% CI, 1% to 18%) in cohort
      A, and in one of 32 patients (95% CI, 0% to 16%) in cohort B. Clinical regression
      or stable disease was achieved in 33 of 77 patients (43%). Tumor regression
      lasted between 0.6 and 23.4 months with 29% of patients achieving response
      lasting longer than 3 months. The progression-free survival (2.4 v 2.3 months; P
      = .4) and overall survival (7.1 v 6.0 months; P = .4) were similar in both
      cohorts. There was one treatment-related death, and 47 patients (33 cohort A, 24
      cohort B) experienced grade 3 or 4 toxicity. CONCLUSION: Sunitinib did not
      achieve the predetermined threshold of >or= 20% activity defined by Response
      Evaluation Criteria in Solid Tumors. However, antitumor responses were observed,
      identifying the vascular endothelial growth factor axis as a viable pathway for
      UC treatment. The reported clinical benefit in previously treated patients
      warrants further investigation in a disease for which there is no US Food and
      Drug Administration-approved treatment.

PMID- 20142594
TI  - Facilitating informed decisions regarding microsatellite instability testing
      among high-risk individuals diagnosed with colorectal cancer.
AB  - PURPOSE: To evaluate the impact of a CD-ROM intervention in the education of
      patients with suspected Lynch syndrome (LS) about microsatellite instability
      (MSI) and immunohisochemistry (IHC) testing. PATIENTS AND METHODS: Two hundred
      thirteen patients meeting Bethesda criteria were randomly assigned to receive
      either a brief educational session with a health educator (n = 105) or a brief
      educational session plus a CD-ROM (n = 108). Assessments were administered at
      baseline and 2 weeks post-treatment. Primary outcomes included MSI and IHC
      knowledge and level of satisfaction with and completeness of the preparation to
      make the decision for MSI testing. Secondary outcomes included decisional
      conflict, difficulty making the decision, cancer-specific and global anxiety, and
      level of discussion about MSI testing with family and friends. RESULTS:
      Participants in the education plus CD-ROM condition reported significant
      increases in knowledge about the MSI and IHC tests, greater satisfaction with the
      preparation to make a decision for testing, lower decisional conflict, and
      greater decisional self-efficacy. The effects of the education plus CD-ROM on
      most outcomes were not moderated by preintervention levels of exposure to MSI
      testing, family support for MSI testing, or the family history of cancer.
      CONCLUSION: Incorporation of new media education strategies for individuals at
      risk for LS may be a valuable component of the informed consent process. As
      clinical criteria for MSI and IHC testing continue to expand, the need for
      alternative educational approaches to meet this increased demand could be met by
      the self-administered computer-based strategy that we described.

PMID- 20142595
TI  - Phase II, randomized, open-label study of pegfilgrastim-supported VDC/IE
      chemotherapy in pediatric sarcoma patients.
AB  - PURPOSE: This multicenter, randomized, open-label study evaluated the efficacy,
      safety, and pharmacokinetics of a single subcutaneous pegfilgrastim injection
      with daily subcutaneous filgrastim administration in pediatric patients receiving
      myelosuppressive chemotherapy for sarcoma. PATIENTS AND METHODS Forty-four
      patients with previously untreated, biopsy-proven sarcoma stratified into three
      age groups (0-5, 6-11, and 12-21 years) were randomly assigned in a 6:1
      randomization ratio to receive a single pegfilgrastim dose of 100 microg/kg (n =
      38) or daily filgrastim doses of 5 microg/kg (n = 6) after chemotherapy (cycles 1
      and 3: vincristine-doxorubicin-cyclophosphamide; cycles 2 and 4: ifosfamide
      etoposide). The duration of grade 4 neutropenia, time to neutrophil recovery,
      incidence of febrile neutropenia, and adverse events were recorded. Results
      Pegfilgrastim and filgrastim were similar for all efficacy and safety end points,
      and their pharmacokinetic profiles were consistent with those in adults. Younger
      children experienced more protracted neutropenia and had higher median
      pegfilgrastim exposure than older children. CONCLUSION A single dose of
      pegfilgrastim at 100 microg/kg administered once per chemotherapy cycle is
      comparable to daily injections of filgrastim at 5 microg/kg for pediatric sarcoma
      patients receiving myelosuppressive chemotherapy.

PMID- 20142596
TI  - Mature results of an individualized radiation dose prescription study based on
      normal tissue constraints in stages I to III non-small-cell lung cancer.
AB  - PURPOSE: We previously showed that individualized radiation dose escalation based
      on normal tissue constraints would allow safe administration of high radiation
      doses with low complication rate. Here, we report the mature results of a
      prospective, single-arm study that used this individualized tolerable dose
      approach. PATIENTS AND METHODS: In total, 166 patients with stage III or
      medically inoperable stage I to II non-small-cell lung cancer, WHO performance
      status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of
      lungs for carbon monoxide >or= 30% were included. Patients were irradiated using
      an individualized prescribed total tumor dose (TTD) based on normal tissue dose
      constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a
      maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential
      chemoradiation was administered. The primary end point was overall survival (OS),
      and the secondary end point was toxicity according to Common Terminology Criteria
      of Adverse Events (CTCAE) v3.0. RESULTS: The median prescribed TTD was 64.8 Gy
      (standard deviation, +/- 11.4 Gy) delivered in 25 +/- 5.8 days. With a median
      follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7%
      and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross
      tumor volume significantly decreased OS (P < .001). Both acute (grade 3, 21.1%;
      grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable.
      CONCLUSION: Individualized prescribed radical radiotherapy based on normal tissue
      constraints with sequential chemoradiation shows survival rates that come close
      to results of concurrent chemoradiation schedules, with acceptable acute and late
      toxicity. A prospective randomized study is warranted to further investigate its
      efficacy.

PMID- 20142597
TI  - Cellular histone modification patterns predict prognosis and treatment response
      in resectable pancreatic adenocarcinoma: results from RTOG 9704.
AB  - PURPOSE Differences in cellular levels of histone modifications have predicted
      clinical outcome in certain cancers. Here, we studied the prognostic and
      predictive value of three histone modifications in pancreatic adenocarcinoma.
      METHODS Tissue microarrays (TMAs) from two pancreatic adenocarcinoma cohorts were
      examined, including those from a 195-patient cohort from Radiation Therapy
      Oncology Group trial RTOG 9704, a multicenter, phase III, randomized treatment
      trial comparing adjuvant gemcitabine with fluorouracil and a 140-patient cohort
      of patients with stage I or II cancer from University of California, Los Angeles
      Medical Center. Immunohistochemistry was performed for histone H3 lysine 4
      dimethylation (H3K4me2), histone H3 lysine 9 dimethylation (H3K9me2), and histone
      H3 lysine 18 acetylation (H3K18ac). Positive tumor cell staining for each histone
      modification was used to classify patients into low- and high-staining groups,
      which were related to clinicopathologic parameters and clinical outcome measures.
      Results Low cellular levels of H3K4me2, H3K9me2, or H3K18ac were each significant
      and independent predictors of poor survival in univariate and multivariate
      models, and combined low levels of H3K4me2 and/or H3K18ac were the most
      significant predictor of overall survival (hazard ratio, 2.93; 95% CI, 1.78 to
      4.82) in the University of California, Los Angeles cohort. In subgroup analyses,
      histone levels were predictive of survival specifically for those patients with
      node-negative cancer or for those patients receiving adjuvant fluorouracil, but
      not gemcitabine, in RTOG 9704. CONCLUSION Cellular levels of histone
      modifications define previously unrecognized subsets of patients with pancreatic
      adenocarcinoma with distinct epigenetic phenotypes and clinical outcomes and
      represent prognostic and predictive biomarkers that could inform clinical
      decisions, including the use of fluorouracil chemotherapy.

PMID- 20142598
TI  - Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in
      relapsed or refractory Waldenstrom macroglobulinemia.
AB  - PURPOSE The phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR)
      signal transduction pathway controls cell proliferation and survival. Everolimus
      is an oral agent targeting raptor mTOR (mTORC1). The trial's goal was to
      determine the antitumor activity and safety of single-agent everolimus in
      patients with relapsed/refractory Waldenstrom macroglobulinemia (WM). PATIENTS
      AND METHODS Eligible patients had measurable disease (immunoglobulin M monoclonal
      protein > 1,000 mg/dL with > 10% marrow involvement or nodal masses > 2 cm), a
      platelet count more than 75,000 x 10(6)/L, a neutrophil count more than 1,000 x
      10(6)/L, and a creatinine and bilirubin less than 2 x the laboratory upper limit
      of normal. Patients received everolimus 10 mg orally daily and were evaluated
      monthly. Tumor response was assessed after cycles 2 and 6 and then every three
      cycles until progression. Results Fifty patients were treated. The median age was
      63 years (range, 43 to 85 years). The overall response rate (complete response
      plus partial remission [PR] plus minimal response [MR]) was 70% (95% CI, 55% to
      82%), with a PR of 42% and 28% MR. The median duration of response and median
      progression-free survival (PFS) have not been reached. The estimated PFS at 6 and
      12 months is 75% (95% CI, 64% to 89%) and 62% (95% CI, 48% to 80%), respectively.
      Grade 3 or higher related toxicities were observed in 56% of patients. The most
      common were hematologic toxicities with cytopenias. Pulmonary toxicity occurred
      in 10% of patients. Dose reductions due to toxicity occurred in 52% of patients.
      CONCLUSION Everolimus has high single-agent activity with an overall response
      rate of 70% and manageable toxicity in patients with relapsed WM and offers a
      potential new therapeutic strategy for this patient group.

PMID- 20142599
TI  - Universal poor survival in children with medulloblastoma harboring somatic TP53
      mutations.
AB  - PURPOSE: Medulloblastoma is the prototype of treatment success in modern
      pediatric neuro-oncology. Unfortunately, 20% to 30% of tumors recur despite
      maximal resection and multimodal therapy. Multiple biologic prognostic markers
      have been investigated to predict recurrences, but controversy remains regarding
      their clinical utility. Because p53 immunopositivity is an adverse prognostic
      marker in pediatric medulloblastoma and TP53 mutations are associated with
      chemotherapy and radiation therapy resistance, we aimed to determine the extent
      and role of TP53 mutations in pediatric medulloblastoma treatment failure.
      PATIENTS AND METHODS: One hundred eight of 111 consecutive patients diagnosed
      with medulloblastoma in our institution from 1995 to 2007 were included. Median
      follow-up time was 5.3 years in survivors. All samples were immunostained for p53
      and erbB-2. Histologic grade and immunostaining were scored by two blinded
      reviewers. For 49 patients, frozen material was available for TP53 sequencing.
      The main outcome measures were overall and progression-free survival. RESULTS:
      Sixteen percent of sequenced medulloblastomas harbored a TP53 mutation. As a
      screening test, p53 immunohistochemistry was 100% sensitive and 83% specific for
      a TP53 mutation. Strikingly, all mutated tumors recurred early, and 5-year
      survival for average-risk patients was 0% for TP53-mutated medulloblastoma
      compared with 74% +/- 8% for wild-type medulloblastoma (P < .0001). Furthermore,
      75% of recurrences in average-risk patients were associated with TP53 mutations.
      On multivariate analysis, TP53 mutation status was the strongest adverse
      prognostic factor (hazard ratio = 10.4, P = .003). CONCLUSION: Lack of long-term
      survival in TP53-mutated medulloblastomas highlights the role of TP53 mutations
      in medulloblastoma resistance to conventional therapies and the need for
      alternative treatments, and prospective validation of these findings is needed.

PMID- 20142600
TI  - Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open
      label, randomized trial evaluating the impact of a pre-Emptive Skin treatment
      regimen on skin toxicities and quality of life in patients with metastatic
      colorectal cancer.
AB  - PURPOSE: Panitumumab, a fully human monoclonal antibody targeting the epidermal
      growth factor receptor (EGFR), is approved in the United States and Europe for
      the treatment of refractory metastatic colorectal cancer (mCRC). Skin toxicities
      are the most common adverse events with EGFR inhibitors. This is the first study
      designed to examine differences between pre-emptive and reactive skin treatment
      for specific skin toxicities in patients with mCRC for any EGFR inhibitor.
      PATIENTS AND METHODS: Patients receiving panitumumab-containing therapy were
      randomly assigned 1:1 to pre-emptive or reactive treatment (after skin toxicity
      developed). Pre-emptive treatment included use of skin moisturizers, sunscreen,
      topical steroid, and doxycycline. The primary end point of the study was the
      incidence of protocol-specified >or= grade 2 skin toxicities during the 6-week
      skin treatment period. Quality of life (QOL) was assessed with the Dermatology
      Life Quality Index (DLQI). RESULTS: Of 95 enrolled patients, 48 received pre
      emptive treatment, and 47 received reactive treatment. The incidence of protocol
      specified >or= grade 2 skin toxicities during the 6-week skin treatment period
      was 29% and 62% for the pre-emptive and reactive groups, respectively. Mean DLQI
      score change from baseline to week 3 was 1.3 points and 4.2 points in the pre
      emptive and reactive groups, respectively. CONCLUSION: The pre-emptive skin
      treatment regimen was well tolerated. The incidence of specific >or= grade 2 skin
      toxicities during the 6-week skin treatment period was reduced by more than 50%
      in the pre-emptive group compared with the reactive group. Patients in the pre
      emptive group reported less QOL impairment than patients in the reactive group.

PMID- 20142601
TI  - Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal
      patients with breast cancer: results from the neuropsychological side study of
      the tamoxifen and exemestane adjuvant multinational trial.
AB  - PURPOSE: To evaluate the influence of adjuvant tamoxifen and exemestane on
      cognitive functioning in postmenopausal patients with breast cancer (BC).
      PATIENTS AND METHODS: Neuropsychological assessments were performed before the
      start (T1) and after 1 year of adjuvant endocrine treatment (T2) in Dutch
      postmenopausal patients with BC, who did not receive chemotherapy. Patients
      participated in the international Tamoxifen and Exemestane Adjuvant Multinational
      trial, a prospective randomized study investigating tamoxifen versus exemestane
      as adjuvant therapy for hormone-sensitive BC. RESULTS: Participants included 80
      tamoxifen users (mean age, 68.7 years; range 51 to 84), 99 exemestane users (mean
      age, 68.3 years; range, 50 to 82), and 120 healthy controls (mean age, 66.2
      years; range, 49 to 86). At T2, after adjustment for T1 performance, exemestane
      users did not perform statistically significantly worse than healthy controls on
      any cognitive domain. In contrast, tamoxifen users performed statistically
      significantly worse than healthy controls on verbal memory (P < .01; Cohen's d =
      .43) and executive functioning (P = .01; Cohen's d = .40), and statistically
      significantly worse than exemestane users on information processing speed (P =
      .02; Cohen's d = .36). With respect to visual memory, working memory, verbal
      fluency, reaction speed, and motor speed, no significant differences between the
      three groups were found. CONCLUSION: After 1 year of adjuvant therapy, tamoxifen
      use is associated with statistically significant lower functioning in verbal
      memory and executive functioning, whereas exemestane use is not associated with
      statistically significant lower cognitive functioning in postmenopausal patients
      with BC. Our results accentuate the need to include assessments of cognitive
      effects of adjuvant endocrine treatment in long-term safety studies.

PMID- 20142602
TI  - Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1-T2
      oral squamous cell carcinomas: results of a prospective multi-institutional
      trial.
AB  - PURPOSE: The validity of sentinel lymph node biopsy (SLNB) for T1 or T2,
      clinically N0, oral cancer was tested by correlation of sentinel node pathologic
      status with that of nodes within the completion neck dissection. METHODS: This
      prospective, cooperative group trial involved 25 institutions over a 3-year
      period. One hundred forty patients with invasive oral cancers, stage T1 and T2,
      N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other
      oral cancers were studied. The study excluded lesions with diameter smaller than
      6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal
      disease. Patients underwent injection of the lesion with (99m)Tc-sulfur colloid,
      nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection.
      The major end point was the negative-predictive value (NPV) of SLNB. RESULTS: In
      the 106 SLNBs, which were found to be pathologically and clinically node-negative
      by routine hematoxylin and eosin stain, 100 patients were found to have no other
      pathologically positive nodes, corresponding to a NPV of 94%. With additional
      sectioning and immunohistochemistry, NPV was improved to 96%. In the forty
      patients with proven cervical metastases, the true-positive rate was 90.2% and
      was superior for tongue tumors relative to floor of mouth. For T1 lesions,
      metastases were correctly identified in 100%. CONCLUSION: For T1 or T2 N0 oral
      squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry,
      performed by surgeons of mixed experience levels, correctly predicted a
      pathologically negative neck in 96% of patients (NPV, 96%).

PMID- 20142603
TI  - Role of cancer treatment in long-term overall and cardiovascular mortality after
      childhood cancer.
AB  - PURPOSE: The purpose of this study was to assess the role of treatment in long
      term overall and cardiovascular mortality after childhood cancer. PATIENTS AND
      METHODS: We studied 4,122 5-year survivors of a childhood cancer diagnosed before
      1986 in France and the United Kingdom. Information on chemotherapy was collected,
      and the radiation dose delivered to the heart was estimated for 2,870 patients
      who had received radiotherapy. RESULTS: After 86,453 person-years of follow-up
      (average, 27 years), 603 deaths had occurred. The overall standardized mortality
      ratio (SMR) was 8.3-fold higher (95% CI, 7.6-fold to 9.0-fold higher) in relation
      to the general populations in France and the United Kingdom. Thirty-two patients
      had died as a result of cardiovascular diseases (ie, 5.0-fold [95% CI, 3.3-fold
      to 6.7-fold] more than expected). The risk of dying as a result of cardiac
      diseases (n = 21) was significantly higher in individuals who had received a
      cumulative anthracycline dose greater than 360 mg/m(2) (relative risk [RR], 4.4;
      95% CI, 1.3 to 15.3) and in individuals who received an average radiation dose
      that exceeded 5 Gy (RR, 12.5 and 25.1 for 5 to 14.9 Gy and > 15 Gy, respectively)
      to the heart. A linear relationship was found between the average dose of
      radiation to the heart and the risk of cardiac mortality (estimated excess
      [corrected] RR at 1 Gy, 60%). CONCLUSION: This study is the first, to our
      knowledge, to establish a relationship between the radiation dose received by the
      heart during radiotherapy for a childhood cancer and long-term cardiac mortality.
      This study also confirms a significant excess risk of cardiac mortality
      associated with a high cumulative dose of anthracyclines.

PMID- 20142604
TI  - A pilot study investigating the effects of trauma, experiential avoidance, and
      disease management in HIV-positive MSM using methamphetamine.
AB  - With high rates of trauma among HIV-positive men who have sex with men (MSM) who
      use methamphetamine, this preliminary pilot study examined the associations
      between experiential avoidance, trauma symptoms, and management of a chronic
      illness. Among a small sample of HIV-positive, methamphetamine-using MSM in a
      California Bay Area County, greater reported experiential avoidance was
      significantly related to greater reported trauma and symptoms of traumatic
      stress. Furthermore, greater reported experiential avoidance was significantly
      related to reduced self-efficacy of illness management and more frequent
      methamphetamine use. Although further research is needed, these data suggest that
      addressing issues of experiential avoidance and trauma could affect behavioral
      choices and treatment outcomes in this high-risk population.

PMID- 20142605
TI  - The problem of time in ethnographic health care research.
AB  - Drawing on the ideas outlined by anthropologist Fabian and feminist scholars
      Halford, Savage, and Witz, in this article I make two arguments that challenge
      ethnography's claim to theoretical inference and empirical generalization,
      particularly for research examining contemporary health care practices. For
      Fabian, the dilemma arose out of ethnography's origins in the secularization of
      time. Accounts of the subject's experiences using present tense assume no
      progress; accounts using past tense freeze the subjects in the past. For Halford
      and her colleagues, the methodological problem was reversed. Their respondents
      were engaged in a battle with health systems in constant change that resulted in
      the loss of memory of a corporate past. The problem now for the ethnographer, as
      in many other research approaches, is one of verification of observations and
      reliability of interpretations. The ethnographer now becomes frozen in time as is
      his or her account of events in the field. Drawing on ethnographic research in
      hospital workplace change, in this article I examine these time-based
      implications for truth claims.

PMID- 20142606
TI  - Comparison of focus groups on cancer and employment conducted face to face or by
      telephone.
AB  - Findings from telephone focus groups have not been compared previously to
      findings from face-to-face focus groups. We conducted four telephone focus groups
      and five face-to-face focus groups in which a single moderator used the same open
      ended questions and discussion facilitation techniques. This comparison was part
      of a larger study to gain a better understanding of employment experiences after
      diagnosis of gynecologic cancer. Offering the telephone option made it easier to
      recruit women from rural areas and geographically distant cities. Interaction
      between participants occurred in both types of focus group. Content analysis
      revealed that similar elements of the employment experience after cancer
      diagnosis were described by telephone and face-to-face participants. Participants
      disclosed certain emotionally sensitive experiences only in the telephone focus
      groups. Telephone focus groups provide useful data and can reduce logistical
      barriers to research participation. Visual anonymity might help some participants
      feel more comfortable discussing certain personal issues.

PMID- 20142607
TI  - Urban aboriginal understandings and experiences of tuberculosis in Montreal,
      Quebec, Canada.
AB  - Tuberculosis (TB) continues to be a serious health issue for some Aboriginal
      populations in Canada. In this article we build on two previous studies partnered
      with an Aboriginal community organization to examine TB in Montreal, Quebec. The
      current study draws on qualitative interviews with Aboriginal participants who
      had either themselves contracted TB or knew someone who had the disease. Thematic
      analysis revealed a high level of experiential knowledge among participants,
      although gaps in biomedical knowledge about the disease and available resources
      were apparent even among those who had been ill. Negative memories and
      experiences relating to the colonial history of TB treatment emerged as
      significant for many participants, helping to explain a silence around the topic
      of TB in the community. Barriers to TB testing were identified, including the
      fear of positive test results, the burden of long-term treatment for either
      latent or active disease, and systemic barriers within and mistrust of the health
      system. Community support for, as well as negative reactions toward, individuals
      ill with TB were identified. We conclude with a number of community health
      lessons to address the treatment and prevention of TB in urban populations.

PMID- 20142608
TI  - Child neurology: past, present, and future: part 2: Present training structure.

PMID- 20142609
TI  - Teaching NeuroImages: MRI in fibrodysplasia ossificans progressiva.

PMID- 20142611
TI  - Visual input is critical for postural control in patients with chronic right
      hemisphere infarcts.

PMID- 20142612
TI  - Altered control of postural sway following cerebral infarction: a cross-sectional
      analysis.
AB  - OBJECTIVE: Balance impairment is common following cerebral infarction. However,
      the effects of lesion hemisphere on postural control are largely unknown. We
      examined dependence upon vision and noninfarcted regional brain tissue volumes
      for postural control in individuals with right and left hemisphere middle
      cerebral artery (MCA) infarcts. METHODS: Subjects with right MCA infarct (n = 17,
      age = 65 +/- 8 years, 7 +/- 6 years poststroke), left MCA infarct (n = 20, age =
      65 +/- 8 years, 7 +/- 6 years poststroke), and controls (n = 55, age = 65 +/- 8
      years) were studied. Postural control was defined by average velocity and the
      range and variability of mediolateral (ML) and anteroposterior (AP) sway during
      eyes-open and eyes-closed standing. Regional brain volumes were quantified using
      anatomic MRI at 3 Tesla. RESULTS: Right and left hemisphere stroke groups had
      similar infarct volumes and outcomes. Subjects with right hemisphere infarcts
      demonstrated greater sway velocity, ML range, and ML variability with eyes closed
      compared to eyes open. In this group, smaller occipital lobe volumes were
      associated with greater eyes-open sway velocity (R = -0.64, p = 0.012) and ML
      range (R = -0.82, p = 0.001). Smaller cerebellar volumes were associated with
      greater eyes-closed sway velocity (R = -0.60, p = 0.015), ML range (R = -0.70, p
      = 0.007), and ML variability (R = -0.85, p < 0.001). These associations were not
      observed in left hemisphere infarct subjects or controls. AP sway was unaffected
      by infarct hemisphere or visual condition and did not correlate with regional
      brain volumes. CONCLUSIONS: Right hemisphere middle cerebral artery infarcts are
      associated with increased dependence on vision and noninfarcted brain regions
      (i.e., occipital lobes, cerebellum) to control postural sway. Strategies
      emphasizing postural tasks under reduced visual conditions may enhance functional
      recovery in these individuals.

PMID- 20142613
TI  - How preserved is episodic memory in behavioral variant frontotemporal dementia?
AB  - OBJECTIVE: Studies have shown variable memory performance in patients with
      behavioral variant frontotemporal dementia (bvFTD). Our study investigated
      whether this variability is due to the admixture of patients with true bvFTD and
      phenocopy patients. We also sought to compare performance of patients with bvFTD
      and patients with Alzheimer disease (AD). METHODS: We analyzed neuropsychological
      memory performance in patients with a clinical diagnosis of bvFTD divided into
      those who progressed (n = 50) and those who remained stable (n = 39), patients
      with AD (n = 64), and healthy controls (n = 64). RESULTS: Patients with
      progressive bvFTD were impaired on most memory tests to a similar level to that
      of patients with early AD. Findings from a subset of patients with progressive
      bvFTD with confirmed FTLD pathology (n = 10) corroborated these findings. By
      contrast, patients with phenocopy bvFTD performed significantly better than
      progressors and patients with AD. Logistic regression revealed that patients with
      bvFTD can be distinguished to a high degree (85%) on the immediate recall score
      of a word list learning test (Rey Auditory Verbal Learning Test). CONCLUSIONS:
      Our results provide evidence for an underlying memory deficit in "real" or
      progressive behavioral variant frontotemporal dementia (bvFTD) similar to
      Alzheimer disease, though the groups differ in orientation scores, with patients
      with bvFTD being intact. Exclusion solely based on impaired neuropsychological
      memory performance can potentially lead to an underdiagnosis of FTD.

PMID- 20142614
TI  - Gene expression levels as endophenotypes in genome-wide association studies of
      Alzheimer disease.
AB  - BACKGROUND: Late-onset Alzheimer disease (LOAD) is a common disorder with a
      substantial genetic component. We postulate that many disease susceptibility
      variants act by altering gene expression levels. METHODS: We measured messenger
      RNA (mRNA) expression levels of 12 LOAD candidate genes in the cerebella of 200
      subjects with LOAD. Using the genotypes from our LOAD genome-wide association
      study for the cis-single nucleotide polymorphisms (SNPs) (n = 619) of these 12
      LOAD candidate genes, we tested for associations with expression levels as
      endophenotypes. The strongest expression cis-SNP was tested for AD association in
      7 independent case-control series (2,280 AD and 2,396 controls). RESULTS: We
      identified 3 SNPs that associated significantly with IDE (insulin degrading
      enzyme) expression levels. A single copy of the minor allele for each significant
      SNP was associated with approximately twofold higher IDE expression levels. The
      most significant SNP, rs7910977, is 4.2 kb beyond the 3' end of IDE. The
      association observed with this SNP was significant even at the genome-wide level
      (p = 2.7 x 10(-8)). Furthermore, the minor allele of rs7910977 associated
      significantly (p = 0.0046) with reduced LOAD risk (OR = 0.81 with a 95% CI of
      0.70-0.94), as expected biologically from its association with elevated IDE
      expression. CONCLUSIONS: These results provide strong evidence that IDE is a late
      onset Alzheimer disease (LOAD) gene with variants that modify risk of LOAD by
      influencing IDE expression. They also suggest that the use of expression levels
      as endophenotypes in genome-wide association studies may provide a powerful
      approach for the identification of disease susceptibility alleles.

PMID- 20142615
TI  - 11C-PIB binding is increased in patients with cerebral amyloid angiopathy-related
      hemorrhage.
AB  - BACKGROUND: The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is
      inferred from clinical and structural imaging features. (11)C-Pittsburgh compound
      B (PIB) is a PET ligand that binds to beta-amyloid in extracellular plaques and
      vessel walls. We hypothesized that patients with a clinical diagnosis of CAA
      related hemorrhage (CAAH) have increased (11)C-PIB uptake and that the pattern
      differs from Alzheimer disease (AD). METHODOLOGY: Patients with CAAH based on
      established clinical criteria were studied using (11)C-PIB PET and were compared
      with age-matched controls and patients with AD. Distribution volume ratio (DVR)
      parametric maps were created using the cerebellar cortex as a reference region.
      RESULTS: Twelve patients with CAAH of mean age 73.9 (range 58-93) years were
      compared with 22 normal controls and 13 patients with AD of mean age 71.8 (59-83)
      and 73.8 (56-90) years, respectively. CAAH PIB median DVR binding was higher in
      cortical regions (1.69, interquartile range 1.44-1.97) compared with controls
      (1.32, 1.21-1.44, p = 0.002) but lower than AD (2.04, 1.93-2.26, p = 0.004). The
      occipital-global uptake ratio was lower among patients with AD than among
      patients with CAAH (p = 0.008), and the frontal-global uptake ratio was higher (p
      = 0.012). CONCLUSION: (11)C-Pittsburgh compound B (PIB) binding is moderately
      increased in most patients with probable cerebral amyloid angiopathy (CAA)
      related intracerebral hemorrhage. The distribution may differ from that seen in
      Alzheimer disease. (11)C-PIB PET may assist in the in vivo diagnosis of CAA and
      serve as a surrogate marker for future therapeutic studies.

PMID- 20142616
TI  - Intracerebral and subarachnoid hemorrhage in patients with cancer.
AB  - OBJECTIVE: To analyze the risk factors, presentation, etiologies, and outcomes of
      adult cancer patients with intracranial hemorrhage (IH). METHODS: We analyzed 208
      patients retrospectively with the diagnosis of IH from the Memorial Sloan
      Kettering neurology database from January 2000 through December 2007. Charts were
      examined for clinical and radiographic data. Survival was calculated using the
      Kaplan-Meier method. Survival between groups was compared via the log-rank test.
      Logistic regression models were used to assess for prognostic indicators of 30-
      and 90-day mortality. RESULTS: There were 181 intracerebral and 46 subarachnoid
      hemorrhages. Sixty-eight percent of patients had solid tumors, 16% had primary
      brain tumors, and 16% had hematopoietic tumors. Hemiparesis and headache were the
      most common symptoms. Intratumoral hemorrhage (61%) and coagulopathy (46%)
      accounted for the majority of hemorrhages, whereas hypertension (5%) was rare.
      Median survival was 3 months (95% confidence interval [CI] 2-4), and 30-day
      mortality was 31%. However, nearly one-half of patients were completely or
      partially independent at the time of discharge. Patients with primary brain
      tumors had the longest median survival (5.9 months, 95% CI 2.9-11.8, p = 0.05).
      Independent predictors of 30-day mortality were not having a primary brain tumor,
      impaired consciousness, multiple foci of hemorrhage, hydrocephalus, no
      ventriculostomy, and treatment of increased intracranial pressure. CONCLUSIONS:
      Intracranial hemorrhage in patients with cancer is often due to unique
      mechanisms. Prognosis is poor, but comparable to intracranial hemorrhage in the
      general population. Aggressive care is recommended despite high mortality,
      because many patients have good functional outcomes.

PMID- 20142617
TI  - Mutant small heat shock protein B3 causes motor neuropathy: utility of a
      candidate gene approach.
AB  - OBJECTIVE: Idiopathic peripheral neuropathy is common and likely due to genetic
      factors that are not detectable using standard linkage analysis. We initiated a
      candidate gene approach to study the genetic influence of the small heat shock
      protein (sHSP) gene family on an axonal motor and motor/sensory neuropathy
      patient population. METHODS: The promoter region and all exonic and intronic
      sequences of the 10 sHSP genes (HSPB1-HSPB10) were screened in a cohort of
      presumed nonacquired, axonal motor and motor/sensory neuropathy patients seen at
      the Ohio State University Neuromuscular Clinic. RESULTS: A missense mutation in
      the gene encoding small heat shock protein B3 (HSPB3, also called HSP27, protein
      3) was discovered in 2 siblings with an asymmetric axonal motor neuropathy.
      Electrophysiologic studies revealed an axonal, predominantly motor, length
      dependent neuropathy. The mutation, HSPB3(R7S), is located in the N-terminal
      domain and involves the loss of a conserved arginine. CONCLUSIONS: The discovery
      of an HSPB3 mutation associated with an axonal motor neuropathy using a candidate
      gene approach supports the notion that the small heat shock protein gene family
      coordinately plays an important role in motor neuron viability.

PMID- 20142618
TI  - Severe epilepsy as the major symptom of new mutations in the mitochondrial
      tRNA(Phe) gene.
AB  - OBJECTIVE: To present 2 families with maternally inherited severe epilepsy as the
      main symptom of mitochondrial disease due to point mutations at position 616 in
      the mitochondrial tRNA(Phe) (MT-TF) gene. METHODS: Histologic stainings were
      performed on skeletal muscle slices from the 2 index patients. Oxidative
      phosphorylation activity was measured by oxygraphic and spectrophotometric
      methods. The patients' complete mitochondrial DNA (mtDNA) and the relevant mtDNA
      region in maternal relatives were sequenced. RESULTS: Muscle histology showed
      only decreased overall COX staining, while a combined respiratory chain defect,
      most severely affecting complex IV, was noted in both patients' skeletal muscle.
      Sequencing of the mtDNA revealed in both patients a mutation at position 616 in
      the MT-TF gene (T>C or T>G). These mutations disrupt a base pair in the anticodon
      stem at a highly conserved position. They were apparently homoplasmic in both
      patients, and had different heteroplasmy levels in the investigated maternal
      relatives. CONCLUSIONS: Deleterious mutations in the mitochondrial tRNA(Phe) may
      solely manifest with epilepsy when segregating to homoplasmy. They may be
      overlooked in the absence of lactate accumulation and typical mosaic
      mitochondrial defects in muscle.

PMID- 20142619
TI  - Availability of brain serotonin transporters in patients with restless legs
      syndrome.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors have been associated with the
      risk of restless legs syndrome (RLS), suggesting that dysregulation of
      serotonergic neurotransmission may provoke or exacerbate RLS. METHODS: We
      compared the availability of serotonin transporter (SERT) between 16 drug-naive
      patients with RLS and 16 healthy controls. SERT was measured in the pons and
      medulla via [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane (beta-CIT)
      SPECT. A ratio of specific to nonspecific brain uptake (V(3)'') was used for all
      comparisons. RLS was diagnosed according to the criteria proposed by the National
      Institute of Health, and its severity was measured using the International RLS
      Study Group (IRLSSG) Severity Scale. RESULTS: The availability of SERT was
      similar in the RLS group and the control group with regards to the pons (1.24 +/-
      0.31 vs 1.24 +/- 0.25, p > 0.1) and the medulla (0.99 +/- 0.25 vs 1.00 +/- 0.23,
      p > 0.1). However, IRLSSG Severity Scale scores increased with decrease of SERT
      availability in both the pons (beta = -0.50, t = -3.19, p = 0.009) and the
      medulla (beta = -0.42, t = -2.44, p = 0.03). CONCLUSIONS: Although serotonin
      transporter (SERT) availability in pons and medulla was similar in the restless
      legs syndrome (RLS) group and the control group, the severity of RLS symptoms
      increased as the availability of SERT decreased. These data partially support the
      hypothesis that an increase of serotonergic neurotransmission in the brainstem
      may exacerbate RLS, possibly via dual modulations on striatal dopaminergic
      neurotransmission and on the activities of spinal motor and sensory neurons.

PMID- 20142620
TI  - Phenotype of a patient with recessive centronuclear myopathy and a novel BIN1
      mutation.

PMID- 20142621
TI  - Severe cutaneous Candida infection during natalizumab therapy in multiple
      sclerosis.

PMID- 20142622
TI  - Reflections: neurology and the humanities. Reflections for February: An economy
      of words.

PMID- 20142623
TI  - Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH 2.

PMID- 20142624
TI  - Teaching NeuroImages: The full-blown neuroimaging of Wernicke encephalopathy.

PMID- 20142625
TI  - Exploring sex disparity in sentencing outcomes: a focus on narcotics offenders in
      South Korea.
AB  - Most research on sentencing outcomes reveals that legally relevant factors such
      as the seriousness of the offense and prior criminal record are primary
      determinants. There is, however, a substantial body of research that finds that
      extralegal factors such as a defendant's sex also influence these outcomes. Most
      of these latter studies conclude that female defendants receive less severe
      outcomes compared to their male counterparts. Most of this research, however, is
      limited to Western societies. To extend this body of research, the current study
      examines sex differences in sentencing practices for a sample of narcotics
      offenders in South Korea. Results support previous research; female drug
      offenders in South Korea are generally treated more leniently than their male
      counterparts. Tests for interaction effects reveal that the defendant's sex also
      interacts with other constellations of factors to produce lenient treatment for
      certain female defendants. These tests, however, also reveal that lenient
      sentence outcomes are not extended to all female defendants; those with prior
      drug convictions do not fare better than their male counterparts at the
      incarceration decision.

PMID- 20142626
TI  - Review: verbal agitation in dementia: the role of discomfort.
AB  - Verbal agitation (VA) is a disturbing and commonly observed behavioral symptom in
      people with dementia. Although several different variables contribute to VA, it
      seems that discomfort plays an important role. The overall objective of this
      article is to review the relationship between VA and discomfort among people with
      dementia. Specifically, this article discusses the place of discomfort within the
      conceptualizations of VA, empirical support for the association between
      discomfort and VA, and practical implications of this relationship in the
      assessment and treatment of VA. This article contributes to a better
      understanding of VA and provides recommendations for prevention and effective
      intervention.

PMID- 20142627
TI  - Effects of apolipoprotein E-epsilon4 and -epsilon2 in amnestic mild cognitive
      impairment and dementia in Shanghai: SCOBHI-P.
AB  - OBJECTIVE: To determine apolipoprotein E (APOE)-epsilon4 and -epsilon2
      frequencies and risk of mild cognitive impairment (MCI) and dementia in Shanghai,
      China. METHODS: A total of 34 MCI and 34 dementia cases were recruited from an
      urban Memory Disorders Clinic and 32 controls were recruited from a residential
      community served by the clinic. Apolipoprotein E was genotyped using standard
      methods. RESULTS: Among controls, frequencies were epsilon2, 0.11; epsilon3,
      0.84; and epsilon4, 0.05; among MCI, 0.05, 0.77, and 0.18; and for dementia,
      0.02, 0.84, and 0.15, respectively. In education-adjusted models, the odds ratio
      (OR) = 5.6 for dementia (95% CI = 1.09-29.3) and 4.7 for MCI (95% CI = 0.90-25.2)
      associated with any epsilon4 allele. The epsilon2 allele was inversely associated
      with dementia (OR = 0.12, 95% CI = 0.013-0.997) and MCI (OR = 0.38, 95% CI = 0.08
      1.61). CONCLUSIONS: APOE-epsilon4 increases and -epsilon2 decreases the risk of
      dementia vs normal cognition. Similar trends were observed for amnestic mild
      cognitive impairment (aMCI).

PMID- 20142629
TI  - Renal resistive index--a valid tool to assess renal endothelial function in
      humans?
AB  - BACKGROUND: In humans, renal endothelial function is assessed by the
      vasoconstrictive response to L-NG-monomethyl arginine (L-NMMA). We hypothesized
      that Doppler sonographic measurements of the renal resistive index in response to
      inhibition of nitric oxide synthase offer a new methodological approach for
      testing renal endothelial function. METHODS: Forty-one patients without
      nephropathy were included. Para-aminohippurate and inulin clearance were
      performed under basal conditions and during L-NMMA infusion. In parallel, renal
      resistive index was assessed by Doppler sonography, and central blood pressure
      was determined. RESULTS: Following nitric oxide synthase inhibition, renal
      resistive index increased significantly, and 29% of our patients developed
      Doppler sonographic diastolic zero flow. Renal plasma flow decreased in response
      to L-NMMA, and conversely, renal vascular resistance increased. There was no
      correlation of renal vascular resistance and renal resistive index at baseline
      and during nitric oxide synthase inhibition. Changes in renal resistive index
      were not related to changes in renal perfusion or renal vascular resistance.
      Renal resistive index correlated with central pulse pressure at baseline and
      during L-NMMA infusion, whereas renal vascular resistance did not correlate with
      central pulse pressure. CONCLUSION: Our data do not support the hypothesis that
      renal resistive index is a tool to test renal endothelial function in humans and
      should not be used interchangeably with renal vascular resistance.

PMID- 20142628
TI  - Factors influencing driving status in an older Latino population.
AB  - OBJECTIVE: The study aims at examining factors associated with driving status and
      self-reported driving difficulty, with particular attention to vision and
      cognitive impairment. METHOD: This study uses cross-sectional data from 421
      elderly Latino participants in the Los Angeles Latino Eye Study (LALES) along
      with cognitive screening, and comparison is by driving status (currently driving,
      used to drive, never drove) and self-reported difficulty driving among current
      drivers. RESULTS: Current drivers were more educated and reported better
      health.Those who never drove were less acculturated.Those who gave up driving had
      more visual impairment and lower scores on mental status testing. Self-reported
      difficulties among current drivers were associated with more health problems but
      not cognitive difficulties. DISCUSSION: Elderly Latinos have a lower driving rate
      than the general older population. There are significant differences between
      older Latinos who continue to drive versus those who never drove or have stopped
      driving. Poorer cognitive performance and poorer vision are associated with
      driving cessation.

PMID- 20142630
TI  - Arterial stiffness and the response to carotid sinus massage in older adults.
AB  - BACKGROUND AND AIMS: Carotid sinus hypersensitivity (CSH) is a common cause of
      fainting and falls in the older adult population and is diagnosed by carotid
      sinus massage (CSM). Previous work has suggested that age-related stiffening of
      blood vessels reduces afferent input from the carotid sinus leading to central
      upregulation of the overall arterial baroreflex response. We examined the
      differences in arterial stiffness and baroreflex function in older adults at high
      cardiovascular risk (advanced age, Type 2 diabetes, hypertension and
      hyperlipidemia) with and without CSH. METHODS: Forty-three older adults (mean age
      71.4+/-0.7) with Type 2 diabetes, hyperlipidemia and hypertension were recruited.
      After resting supine for 45 minutes prior to the start of data collection, each
      subject had arterial stiffness measured by pulse wave velocity (PWV, Complior
      SD), followed by spontaneous baroreflex measures (Baroreflex sensitivity, BRS)
      and CSM. RESULTS: Of the 43 subjects tested, 10 subjects met the criteria for CSH
      (8 pure vasodepressor and 2 mixed CSH). CSH subjects had higher measures of
      arterial stiffness when compared to normal subjects for both radial PWV (11.5+/
      0.6 vs 9.6+/-0.4 m/s, p=0.043) and femoral PWV (13.4+/-0.9 vs 11.0+/-0.5 m/s,
      p=0.036). The CSH group demonstrated significantly lower BRS as compared to the
      normal group (BRS, 6.73+/-0.58 vs 10.41+/-0.85 ms/mmHg, p=0.038). These results
      were unchanged when the analysis was repeated with only the VD subjects.
      CONCLUSIONS: Older adults with CSH have higher arterial stiffness and reduced
      arterial baroreflex sensitivity. There was no evidence to support upregulation of
      the arterial baroreflex in patients with CSH.

PMID- 20142631
TI  - Adiponectin-leptin ratio: a useful estimate of insulin resistance in patients
      with Type 2 diabetes.
AB  - AIMS: Adiponectin and leptin are adipocytokines associated with insulin
      resistance. The objective of this study was to evaluate the performance of the
      adiponectin-leptin ratio as a measure of insulin resistance in comparison with
      other surrogate measures of insulin resistance based on fasting insulin and
      glucose levels [homeostasis model assessment (HOMA), quantitative insulin
      sensitivity check index (QUICKI), fasting glucose/insulin ratio] and with
      measures based on fasting insulin and triglyceride levels (McAuley index) in
      Caucasian patients with Type 2 diabetes (T2D). METHODS: In 70 patients included
      in DEMAND (delapril and manidipine for nephroprotection in diabetes) study,
      fasting samples of plasma insulin and adiponectin were determined by a
      radioimmunoassay, whereas plasma leptin was determined by an enzyme-linked
      immunosorbent assay. Insulin resistance estimates were derived by the established
      equations and compared with the direct measurement of insulin resistance obtained
      with the euglycemic hyperinsulinemic clamp. Insulin resistance estimates and the
      clamp derived sensitivity index were compared by correlation analysis. RESULTS:
      The adiponectin-leptin ratio correlated best with the clamp derived sensitivity
      index (r=0.553, p<0.001) compared to other surrogate measures of insulin
      resistance. In multiple linear regression models including different surrogate
      measures of insulin resistance as independent predictors of the sensitivity
      index, the model with the adiponectin-leptin ratio accounted for the highest
      variability of the sensitivity index (r2=0.336, p<0.001). CONCLUSIONS: The
      adiponectin-leptin ratio is associated with insulin resistance, measured with the
      euglycemic hyperinsulinemic clamp, in Caucasians with T2D. The association with
      clamp derived sensitivity index is even stronger than that of HOMA, QUICKI,
      fasting glucose/insulin ratio or McAuley index and is independent of body mass
      index or glycemic control. The adiponectin-leptin ratio promises to become a new
      laboratory marker of insulin resistance in T2D.

PMID- 20142632
TI  - ACTH and cortisol responses to ghrelin and desmopressin in patients with
      Cushing's disease and adrenal enlargement.
AB  - BACKGROUND: Overexpression of ghrelin and vasopressin (V3) receptors demonstrated
      on corticotrophe adenomas accounts for exaggerated ACTH and cortisol responses to
      ghrelin and desmopressin (DDAVP) in patients with Cushing's disease (CD). AIM: In
      this study we have compared ACTH and cortisol responsiveness to DDAVP and ghrelin
      in CD patients with and without adrenal enlargement. SUBJECTS AND METHODS:
      Ghrelin and DDAVP tests were performed in 15 patients with CD (7 with and 8
      without signs of adrenal enlargement) with CRH test in 8 patients. In 7 age and
      sex-matched healthy subjects, ghrelin test was performed. Plasma ACTH and serum
      cortisol concentrations were measured after ghrelin, DDAVP and CRH. Growth
      hormone was measured after stimulation with ghrelin. RESULTS: Significantly
      higher baseline and peak ACTH and cortisol concentrations after ghrelin were
      observed in all patients with CD compared to healthy control subjects. Patients
      with CD and adrenal enlargement had significantly lower baseline and peak ACTH
      concentrations after stimulation with ghrelin compared to CD patients without
      adrenal enlargement, while cortisol levels at baseline and after ghrelin
      administration were similar. Three out of seven patients with CD and adrenal
      enlargement did not respond to DDAVP while they responded well to CRH and
      ghrelin. CONCLUSION: Patients with CD and adrenal enlargement pose special
      diagnostic problems. They may have lower baseline ACTH levels and may not respond
      to DDAVP while they respond to ghrelin and CRH. Despite increased endogenous
      cortisol levels in CD, cortisol responses to ghrelin and CRH are preserved in
      patients with CD and adrenal enlargement.

PMID- 20142633
TI  - Intracranial ependymoma associated with multiple endocrine neoplasia type 1.

PMID- 20142638
TI  - Vaginal surgery. Foreword.

PMID- 20142634
TI  - Two weekly sessions of combined aerobic and resistance exercise are sufficient to
      provide beneficial effects in subjects with Type 2 diabetes mellitus and
      metabolic syndrome.
AB  - This study was performed to establish whether only 2 sessions per week of
      combined aerobic and resistance exercise are enough to reduce glycated hemoglobin
      (HbA(1c)) and to induce changes in skeletal muscle gene expression in Type 2
      diabetes mellitus (DM2) subjects with metabolic syndrome. Eight DM2 subjects
      underwent a 1-yr exercise program consisting of 2 weekly sessions of 140 min that
      combined aerobic [at 55-70% of maximal oxygen uptake (VO(2max))] and resistance
      circuit training [at 60-80% of 1 repetition maximum (RM)]. The training
      significantly improved VO(2max) (from 33.5+/-3.8 ml/kg/min to 38.2+/-3.5
      ml/kg/min, p=0.0085) and muscle strength (p<0.05). Changes over baseline were
      significant for HbA(1c), reduced by 0.45% (p=0.0084), fasting blood glucose (from
      8.8+/-1.5 to 6.9+/-2.2 mmol/l, p=0.0132), waist circumference (from 98.9+/-4.8 to
      95.9+/-4.6 cm, p=0.0054), body weight (from 87.5+/-10.7 to 85.7+/-10.1 kg,
      p=0.0375), systolic blood pressure (from 137+/-15 to 126+/-8 mmHg, p=0.0455),
      total cholesterol (from 220+/-24 to 184+/-13 mg/dl, p=0.0057), and LDL
      cholesterol (from 150+/-16 to 105+/-15 mg/dl, p=0.0004). Mitochondrial
      DNA/nuclear DNA ratio at 6 and 12 months did not change. There was a significant
      increase of mRNA of peroxisome proliferator- activated receptor (PPAR)-gamma
      after 6 months of train - ing (p=0.024); PPARalpha mRNA levels were significantly
      increased at 6 (p=0.035) and 12 months (p=0.044). The mRNA quantification of
      other genes measured [mitochondrially encoded cytochrome c oxidase subunit II
      (MTCO2), cytochrome c oxidase subunit Vb (COX5b), PPARgamma coactivator 1alpha
      (PGC- 1alpha), glucose transporter 4 (GLUT 4), forkhead transcription factor BOX
      O1 (FOXO-1), carnitine palmitoyltransferase 1 (CPT-1), lipoprotein lipase (LPL),
      and insulin receptor substrate 1 (IRS-1)] did not show significant changes at 6
      and 12 months. This study suggests that a twice-per-week frequency of exercise is
      sufficient to improve glucose control and the expression of skeletal muscle
      PPARgamma and PPARalpha in DM2 subjects with metabolic syndrome.

PMID- 20142635
TI  - A study of central serotoninergic activity in healthy subjects and patients with
      Type 2 diabetes treated by traditional one-to-one care or Group Care.
AB  - AIM: Central serotoninergic activity may modulate glucose metabolism via
      neuroendocrine effectors. Group Care is a clinico-pedagogic intervention that
      improves metabolic control and quality of life in Type 2 diabetes through
      lifestyle modification and, possibly, central mechanisms. The hypothesis that
      central serotoninergic activity is modified in patients followed by Group Care
      was tested by measuring their hypothalamic- pituitary-adrenal response to
      citalopram, a selective serotonin reuptake inhibitor. METHODS AND SUBJECTS: Ten
      healthy controls and 17 non-obese, non-insulin-treated patients with Type 2
      diabetes received, in random order, iv infusions of either 20 mg citalopram or
      saline. Nine patients had been longterm on Group Care and 8 had always been on
      traditional one-to-one care. Circulating glucose, insulin, ACTH, cortisol, DHEA,
      GH and PRL were measured every 15 min for 240 min. Differences between areas
      under the curves after citalopram and saline (Delta-AUC) were calculated.
      RESULTS: Citalopram stimulated ACTH and cortisol secretion in healthy subjects
      (p=0.026 and p=0.011, respectively) and patients on Group Care (p=0.056 and
      p=0.038) but not in patients on traditional care. In healthy subjects, basal
      glucose correlated with growth hormone Delta- AUC (r=0.820; p=0.004) and
      inversely with insulin Delta-AUC (r=-0.822; p=0.003). The former correlation was
      preserved in the patients (r=0.637; p=0.026). CONCLUSIONS: Diabetes may blunt the
      response of the hypothalamic-pituitary-adrenal axis to citalopram, but this is
      preserved in patients followed by a long-term intervention model that improves
      clinical as well as cognitive and emotional variables.

PMID- 20142639
TI  - Vaginal hysterectomy for benign disease without prolapse.
AB  - Vaginal hysterectomy was the first minimally invasive surgical approach for
      benign gynecologic conditions. Recently a number of other approaches for
      hysterectomy have been introduced, yet when compared with vaginal hysterectomy
      these approaches do not offer significant benefit for similar indications. The
      focus of this chapter is to provide comprehensive review of vaginal hysterectomy
      for the practicing clinician.

PMID- 20142640
TI  - Removal of adnexa at the time of vaginal hysterectomy.
AB  - Removal of the fallopian tubes and ovaries at the time of vaginal hysterectomy is
      a skill that must be acquired if one is to be a competent vaginal surgeon.
      Various techniques have been described and will be reviewed in this chapter. A
      single technique or series of steps often must be modified depending on the
      descent of the adnexa, size and shape of the pelvis, and intraperitoneal
      pathology. The pelvic surgeon must adhere to the basic surgical principles and
      understand the anatomic relationships of the adnexa to other pelvic viscera,
      including the lower urinary tract. Preoperative discussion with all patients
      regardless of age is imperative in determining their desires for oophorectomy at
      the time of vaginal hysterectomy.

PMID- 20142641
TI  - Vaginal hysterectomy for the prolapsed uterus.
AB  - Although most gynecologists are comfortable performing vaginal hysterectomy in
      the patient without significant uterovaginal prolapse, vaginal hysterectomy for
      the prolapsed uterus poses unique challenges and requires an increased awareness
      of deviations in pelvic anatomy that may result. This review article discusses
      the background of vaginal hysterectomy performed for uterovaginal prolapse, the
      pathophysiology of uterovaginal prolapse, preoperative assessment of the patient
      with uterovaginal prolapse, surgical technique, ureteral anatomy, techniques to
      avoid injury to the ureter at the time of vaginal hysterectomy for uterovaginal
      prolapse, and other relevant considerations.

PMID- 20142642
TI  - Difficult vaginal hysterectomy.
AB  - A difficult vaginal hysterectomy can challenge the most accomplished pelvic
      surgeon. Large uterine size or prior pelvic surgery is commonly thought to make a
      vaginal hysterectomy more difficult, but more common issues such as large body
      habitus or extensive prolapse may make performing a vaginal hysterectomy even
      more technically challenging. The knowledge and expertise needed to perform a
      routine vaginal hysterectomy are prerequisites for managing more difficult cases.
      As techniques in pelvic surgery continue to evolve, it is critical that this
      minimally invasive procedure continue to be taught and performed.

PMID- 20142643
TI  - Anterior vaginal wall prolapse: assessment and treatment.
AB  - Assessment and management of anterior vaginal wall defects presents a unique
      surgical challenge. It is often the most common site of initial prolapse in women
      and the most common site of recurrence. This chapter discusses the anatomy,
      evaluation, and surgical approach to the treatment of anterior vaginal wall
      defects. We also review outcomes of various surgical approaches and discuss why
      the anterior vaginal wall presents such a challenge.

PMID- 20142644
TI  - Posterior wall prolapse and repair.
AB  - Most posterior wall defects occur in combination with other pelvic support
      disorders. Some patients with rectoceles, the most common posterior wall defect,
      are asymptomatic, whereas others experience a range of symptoms from a sensation
      of lower pelvic fullness to defecatory and/or sexual dysfunction. If patients are
      symptomatic, rectoceles can be treated conservatively with pelvic floor
      physiotherapy, behavioral therapy, or pessaries. Surgically, the most common
      rectocele repair is a traditional posterior colporrhaphy which provides excellent
      cure rates of up to 95%. The studies published to date do not support the use of
      biologic or synthetic absorbable grafts in reconstructive surgical procedures of
      the posterior compartment as these repairs have not improved anatomic or
      functional outcomes over traditional posterior colporrhaphy.

PMID- 20142645
TI  - Uterosacral and sacrospinous ligament suspension for restoration of apical
      vaginal support.
AB  - Correction of apical vaginal prolapse has been described via abdominal,
      laparoscopic, and transvaginal approaches. The uterosacral and sacrospinous
      ligament suspension procedures are common transvaginal native tissue repairs to
      restore apical vaginal support. Preoperative evaluation, operative decision
      making, surgical techniques, and objective and subjective outcomes of each
      technique are reviewed.

PMID- 20142646
TI  - Obliterative procedures for pelvic organ prolapse.
AB  - Colpocleisis is an effective surgical treatment for pelvic organ prolapse in
      elderly women who do not wish to preserve the vagina for sexual intercourse.
      Colpocleisis provides good relief of pelvic floor symptoms without significant
      morbidity. The morbidity and mortality associated with the surgery is largely
      related to the health status of this elderly segment of the population. Stress
      incontinence can be addressed with a concomitant procedure such as a midurethral
      synthetic sling. Overall patient satisfaction with this obliterative procedure is
      greater than 90%. As the population ages, this procedure stands to become an
      increasingly popular treatment option.

PMID- 20142648
TI  - Vaginal surgery for congenital anomalies.
AB  - Congenital anomalies of the vagina may be isolated to the vagina or be part of a
      more complex Mullerian tract anomaly with possible fertility concerns. Patient
      age, complete assessment of the anomaly before surgery, and the psychologic
      implications for the patient are important components of the initial evaluation
      and treatment planning. Imaging, including magnetic resonance imaging, should be
      used to assess the extent of the anomaly and possibly other organ systems
      involved. Surgeries for imperforate hymen, longitudinal septum, and low thin
      transverse septum are relatively straightforward. More complicated surgeries
      should be performed by a specialized surgical team.

PMID- 20142647
TI  - Insertion and removal of vaginal mesh for pelvic organ prolapse.
AB  - A variety of surgical meshes are available to correct pelvic organ prolapse. This
      article discusses benefits and risks of vaginal mesh use. Emphasis is placed on
      the appropriate surgical technique to improve outcomes and minimize mesh
      complications. Placement options are reviewed with the discussion of self
      tailored mesh, trocar-based mesh kits, and non-trocar mesh kits. This article
      also reviews the management of mesh complications including the technique for
      mesh removal.

PMID- 20142649
TI  - Management of vulvovaginal strictures/shortened vagina.
AB  - Vaginal strictures are generally difficult to manage and tend to reccur despite
      appropriate initial therapy. Vaginal dilation with or without surgery is the main
      stay of treatment. Causes, diagnosis and management of the vulvovaginal
      strictures are presented.

PMID- 20142650
TI  - Surgical approaches to postobstetrical perineal body defects (rectovaginal
      fistula and chronic third and fourth-degree lacerations).
AB  - Rectovaginal fistulas and chronic anal sphincter lacerations are uncommon
      complications that are most often secondary to vaginal delivery, gynecologic
      surgery, and inflammatory bowel disease. In this chapter, we will review the
      pertinent anatomy, focusing on the 6 structures that should be considered during
      the repair and surgical techniques to promote restoration on normal anatomy and
      function. Key concepts include a tension-free repair, meticulous hemostasis, and
      postoperative bowel management.

PMID- 20142651
TI  - Postpartum hemorrhage. Foreword.

PMID- 20142652
TI  - Postpartum hemorrhage: epidemiology, risk factors, and causes.
AB  - Postpartum hemorrhage (PPH) is a leading cause of death and morbidity relating to
      pregnancy. Uterine atony is the leading cause of PPH, and trauma, including
      iatrogenic trauma, increases the risk for postpartum hemorrhage. Women with PPH
      in a pregnancy are at increased risk of PPH in a subsequent pregnancy. Awareness
      of these facts, and anticipation and prevention of uterine atony, as well as
      avoiding unnecessary cesareans, episiotomies, and other genital tract trauma have
      the potential to significantly reduce the mortality and morbidity from postpartum
      hemorrhage. The epidemiology of postpartum hemorrhage, including the incidence
      and temporal trends as well as the causes and risk factors associated with it are
      presented.

PMID- 20142653
TI  - Clinical evaluation during postpartum hemorrhage.
AB  - Obstetric hemorrhage remains the most important cause of maternal mortality
      worldwide, accounting for 30% of all direct maternal deaths. As the method of
      management depends on multiple concurrent and sequential evaluations of the
      patient's status, it is helpful to have an evaluation strategy prepared for when
      a postpartum hemorrhage is encountered to facilitate interventions. This review
      describes an etiology-based approach to the clinical evaluation of postpartum
      hemorrhage and a suggested systems process that allows both a timely and
      appropriate evaluation of the hemorrhaging mother.

PMID- 20142654
TI  - Postpartum hemorrhage: evidence-based medical interventions for prevention and
      treatment.
AB  - Postpartum hemorrhage (PPH) remains a significant contributor to maternal
      morbidity and mortality throughout the world. The majority of research on this
      topic has focused on efforts to prevent PPH. Sound data exist that active
      management of the third stage of labor can reduce the occurrence of PPH. Although
      there remains debate regarding the optimal protocol for active management, it
      appears at this time that oxytocin is the preferable uterotonic to use.
      Misoprostol may be a reasonable option where parenteral administration of an
      uterotonic is not feasible. There is little evidence to guide treatment decisions
      should PPH occur.

PMID- 20142655
TI  - Surgical remedies for postpartum hemorrhage.
AB  - When medical therapy is unsuccessful, surgical approaches to postpartum
      hemorrhage are often considered. These may include uterine curettage, laceration
      repair, balloon tamponade, compressive suture techniques, uterine or hypogastric
      artery ligation, and ultimately hysterectomy. A systems approach to the care of
      these patients includes identification of rapid response teams, assessment of
      risk factors, and the timely and knowledgeable use of blood and blood products.
      Comprehensive care of patients with massive obstetric hemorrhage will improve the
      outcome of this largely preventable cause of maternal mortality.

PMID- 20142656
TI  - Blood product replacement for postpartum hemorrhage.
AB  - Hemorrhage requiring blood transfusion is a common occurrence in obstetrics. This
      article reviews each step in the transfusion process, including laboratory
      preparation of blood, indications for various blood components, complications of
      blood transfusion, massive transfusion, and alternatives to homologous blood.
      Current thinking regarding transfusion-related acute lung injury, transfusion
      related immunomodulation, early use of plasma for massive transfusion, and the
      use of adjuvant agents such as activated recombinant factor VII are also
      discussed.

PMID- 20142657
TI  - Endovascular treatment of postpartum hemorrhage.
AB  - Transcatheter arterial embolization is a minimally invasive intervention
      developed from diagnostic angiography. The evolution of endovascular techniques,
      including arterial embolization and the use of occlusion balloons, has
      established a role for the interventional radiologist in the setting of
      uncontrolled postpartum hemorrhage. Arterial embolization of the uterine arteries
      as an alternative to hysterectomy has the advantages of being a minimally
      invasive treatment that preserves uterus without eliminating the possibility of
      future surgical intervention if necessary. Although arterial embolization has
      progressively become a standard of care over the last 30 years, its impact on
      future fertility still remains controversial.

PMID- 20142658
TI  - The use of recombinant activated FVII in postpartum hemorrhage.
AB  - Severe bleeding remains a leading cause of morbidity and mortality in obstetrics.
      The first-line standard treatment of massive postpartum hemorrhage (PPH) includes
      medical measures directed at improving uterine tone, replacement of lost
      intravascular volume, blood and coagulation factors, and surgical or invasive
      procedures. Recently, a number of case reports or case series have reported the
      successful "off-label" use of recombinant activated factor VII (rFVIIa) in PPH
      unresponsive to conventional treatments. In this review, a critical analysis of
      the published literature on the use of rFVIIa in severe PPH was performed.
      Overall, a total of 272 PPH women were collected among the largest case series
      and/or international registries. No randomized controlled trials have been
      conducted in this area. Currently, the literature data suggest that, at a median
      dose of 81.5 microg/kg, rFVIIa is effective in stopping or reducing bleeding in
      85% of the cases. Finally, on the basis of the evidence from the literature and
      on own experience, we included some recommendations and an algorithm on the
      therapeutic role of rFVIIa in the management of PPH.

PMID- 20142659
TI  - Placenta accreta and postpartum hemorrhage.
AB  - Placenta accreta is the abnormal adherence of the placenta to the uterine wall.
      Where placenta accreta is present, the failure of the placenta to separate
      normally from the uterus after delivery is accompanied by severe postpartum
      hemorrhage. The best outcomes in placenta accreta are in prenatally diagnosed
      electively delivered cases. Management should take place in centers with special
      expertise. All obstetric units should have an obstetric hemorrhage protocol in
      place.

PMID- 20142660
TI  - Uterine rupture as a source of obstetrical hemorrhage.
AB  - Uterine rupture is an important cause of obstetrical hemorrhage associated with
      morbidity for mother and fetus. Risk factors should be discussed in the
      counseling process. Intrapartum findings including maternal condition, fetal
      heart rate monitoring, and uterine activity may prove helpful in making the
      diagnosis of a dehiscence or rupture, but ultimately this requires some degree of
      suspicion by the labor and delivery team. As in any case of acute obstetrical
      emergency, preparation and timely mobilization of all necessary personnel is key
      to optimizing outcome.

PMID- 20142661
TI  - Maternal coagulation disorders and postpartum hemorrhage.
AB  - Disorders of coagulation are relatively uncommon as a sole cause of postpartum
      hemorrhage. Coagulation disturbances should be suspected in patients with a
      family history of such abnormalities and patients with a history of menorrhagia.
      Clinical circumstances may also suggest coagulation defect as a cause of
      postpartum hemorrhage. Diagnosis of a coagulation disorder often requires a high
      index of suspicion and should not be overlooked in the evaluation of obstetric
      hemorrhage.

PMID- 20142662
TI  - Team training/simulation.
AB  - Obstetrical emergencies require the rapid formation of a team with clear
      communication, strong leadership, and appropriate decision-making to ensure a
      positive patient outcome. Obstetric teams can improve their emergency response
      capability and efficiency through team and simulation training. Postpartum
      hemorrhage is an ideal model for team and simulation training, as postpartum
      hemorrhage requires a multidisciplinary team with the capability to produce a
      protocol-driven, rapid response. This article provides an overview of team and
      simulation training and focuses on applications within obstetrics, particularly
      preparation for postpartum hemorrhage.

PMID- 20142665
TI  - Current world literature.

PMID- 20142666
TI  - Anaesthesiologists in emergency medicine: the desirable manpower.

PMID- 20142667
TI  - Abstracts of the American Burn Association 42nd Annual Meeting. March 9-12, 2010.
      Boston, Massachusetts, USA.

PMID- 20142670
TI  - Engaging the new wave of second-career nurses.

PMID- 20142671
TI  - Stop "knowledge creep".

PMID- 20142672
TI  - Solving the mystery of patient days and the midnight census.

PMID- 20142673
TI  - Want keepers? Regularly recognize.

PMID- 20142674
TI  - Is this ethical? You DECIDE.

PMID- 20142675
TI  - So good it's unreal: the value of simulation education.

PMID- 20142677
TI  - 12 steps toward policy solutions.

PMID- 20142678
TI  - Med reconciliation: do the right thing.

PMID- 20142679
TI  - The Magnetic Pull: a staff report.

PMID- 20142680
TI  - The journey toward a personal health record.

PMID- 20142681
TI  - Get equipped to navigate the waters of healthcare change.

PMID- 20142682
TI  - Maximizing your hire-ability, honing your entrepreneurial skills.

PMID- 20142683
TI  - Managing our association during times of change.

PMID- 20142685
TI  - Congenital scoliosis with associated rib fusions: nursing care of patients
      following VEPTR insertion.
AB  - Congenital scoliosis with associated rib fusions, flail chest syndrome and
      hypoplastic thorax may create a progressive 3-dimensional deformity of the
      thorax, thereby inhibiting normal lung growth and respiratory function leading to
      respiratory insufficiency. The recently coined term for this condition is
      thoracic insufficiency syndrome (TIS). Traditional spine-based surgical
      procedures to correct congenital scoliosis with rib fusions inhibit the growth of
      the spine further, potentially worsening TIS and leading to respiratory problems
      during young adulthood. The dynamic interaction between the spine, ribs, and
      lungs was not addressed with these spine-focused procedures. This article
      explains TIS, discusses surgical treatment, and highlights unique aspects of
      postoperative nursing care. A case study is used for further explanation.

PMID- 20142687
TI  - Validation of the Osteoporosis Smoking Health Belief instrument.
AB  - Smoking has a deleterious effect on bone mineral density. Psychometric properties
      were conducted for 3 smoking cessation subscales of the Osteoporosis Smoking
      Health Belief (OSHB) instrument: barriers, benefits, and self-efficacy. The
      instrument was evaluated by 6 nurse researchers, administered to a pilot sample
      of 23 adult smokers aged 19-39, and to a convenience sample of 59 adult smokers
      aged 19-84 years attending bingo at churches and community centers. Principal
      components factor analyses were conducted on the 18 items at both time points and
      accounted for 65.05% of the variances in the matrix at Time 1 and 71.19% at Time
      2. The 3 statistical factors corresponded to the theoretically derived concepts.
      Cronbach's alphas for benefits of not smoking were .86 at Time 1 and .88 at Time
      2; for barriers, .78 at Time 1 and .89 at Time 2; and for self-efficacy, .94 at
      Time 1 and .96 at Time 2. The test-retest correlations were .68 for benefits, .74
      for barriers, and .79 for self-efficacy. Paired t tests showed no significant
      change over time. The OSHB meets relevant measurement criteria.

PMID- 20142688
TI  - Tropical pyomyositis caused by salmonella within the gluteus maximus of a
      hepatitis B carrier.
AB  - Tropical pyomyositis, a disease often seen in tropical countries, is
      characterized by suppuration within the skeletal muscles, manifesting as single
      or multiple abscesses. Staphylococcus aureus is the most common agent responsible
      for typical pyomyositis. Misdiagnosis usually occurs as a result of nonspecific
      presentation, unfamiliarity with the disease, and the many possible differential
      diagnoses. Here we present a rare case of tropical pyomyositis caused by
      Salmonella (group D non-typhi Salmonella) within the gluteus maximus of a
      hepatitis B carrier without definite previous gastrointestinal episodes.

PMID- 20142689
TI  - Better pain management after total joint replacement surgery: a quality
      improvement approach.
AB  - Following the implementation of an innovative analgesic and pain management
      pathway for patients undergoing total joint replacement at Virginia Mason Medical
      Center, a multidisciplinary team of providers identified additional pain
      management needs related to patient education and communication. Utilizing
      several quality improvement strategies, including a "gemba walk" and a "Plan, Do,
      Study, Act" methodology, a comprehensive, evidence-based patient education tool
      was developed. The quality improvement process detailed in this article focuses
      on outcomes related to enhanced patient and provider communication, enhanced
      patient education, and accurate provider pain assessment. The framework that is
      presented can be applied to many problems that may exist in the acute care
      setting.

PMID- 20142691
TI  - Improving clinical outcomes with continuous passive motion: an interactive
      education approach.
AB  - Orthopaedic nursing often involves the use of equipment, and nurses may learn
      about the use of equipment on the job in informal ways. Staff may have difficulty
      attending in-services, may be off during quick informal in-services, or may not
      use equipment for a period of time after an in-service. Due to lack of knowledge,
      inconsistency in the implementation of ordered therapies resulting in poor
      outcomes, including pressure wounds and patient dissatisfaction, frequently
      occurs. Using continuous passive motion therapy as an example, an interactive
      educational approach to equipment training is presented. Such an approach helps
      formalize equipment training, provides a standard approach to implementing
      ordered therapy, provides references for staff after in-services, and improves
      patient outcomes.

PMID- 20142693
TI  - Use of inpatient continuous passive motion versus no CPM in computer-assisted
      total knee arthroplasty.
AB  - BACKGROUND: Continuous passive motion (CPM) has shown positive effects on tissue
      healing, edema, hemarthrosis, and joint function (L. Brosseau et al., 2004). CPM
      has also been shown to increase short-term early flexion and decrease length of
      stay (LOS) ( L. Brosseau et al., 2004; C. M. Chiarello, C. M. S. Gundersen, & T.
      O'Halloran, 2004). The benefits of CPM for the population of patients undergoing
      computer-assisted total knee arthroplasty (TKA) have not been examined. PURPOSE:
      The primary objective of this study was to determine whether the use of CPM
      following computer-assisted TKA resulted in differences in range of motion,
      edema/drainage, functional ability, and pain. METHODS: This was an experimental,
      prospective, randomized study of patients undergoing unilateral, computer
      assisted TKA. The experimental group received CPM thrice daily and physical
      therapy (PT) twice daily during their hospitalization. The control group received
      PT twice daily and no CPM during the hospital stay. Both groups received PT after
      discharge. Measurement included Knee Society scores, Western Ontario McMaster
      Osteoarthritis Index values, range of motion, knee circumference, and HemoVac
      drainage. Data were collected at various intervals from preoperatively through 3
      months. RESULTS: Although the control group was found to be higher functioning
      preoperatively, there was no statistically significant difference in flexion,
      edema or drainage, function, or pain between groups through the 3-month study
      period.

PMID- 20142694
TI  - Acetaminophen: old friend--new rules.
AB  - Acetaminophen is an old and comfortable friend. In its over-the-counter forms (of
      which there are almost 100), it is used by millions of people for relief of pain
      and to treat mild fevers. When combined with an opioid as a prescription drug, it
      is often effective for more severe pain. Generally, for most people, when taken
      as directed, acetaminophen has proved to be not only effective but also safe with
      very few adverse effects. However, the relationship between acetaminophen use and
      acute liver damage is not as well known (despite Federal Drug Administration
      [FDA] recommendations for changes that relate to both labeling and use). In this
      article, recent moves by the FDA to make acetaminophen safety are discussed.
      Nurses who are able to educate their patients about the safety issues related to
      acetaminophen will be very important in reducing the incidence of overdose
      related liver failure.

PMID- 20142699
TI  - The challenge of pain in children and adolescents with cerebral palsy.

PMID- 20142700
TI  - Neonatal physical therapy. Part II: Practice frameworks and evidence-based
      practice guidelines.
AB  - PURPOSE: (1) To outline frameworks for neonatal physical therapy based on 3
      theoretical models, (2) to describe emerging literature supporting neonatal
      physical therapy practice, and (3) to identify evidence-based practice
      recommendations. KEY POINTS: Three models are presented as a framework for
      neonatal practice: (1) dynamic systems theory including synactive theory and the
      theory of neuronal group selection, (2) the International Classification of
      Functioning, Disability and Health, and (3) family-centered care. Literature is
      summarized to support neonatal physical therapists in the areas of examination,
      developmental care, intervention, and parent education. Practice recommendations
      are offered with levels of evidence identified. CONCLUSIONS: Neonatal physical
      therapy practice has a theoretical and evidence-based structure, and evidence is
      emerging for selected clinical procedures. Continued research to expand the
      science of neonatal physical therapy is critical to elevate the evidence and
      support practice recommendations.

PMID- 20142701
TI  - The effects of age and gender on the weight and use of schoolbags.
AB  - PURPOSE: To examine age and gender differences in schoolbag use and to compare
      findings in Greece with those of other countries. METHOD: Schoolbag weight and
      carrying characteristics were assessed in 703 boys and girls aged 6 to 14 years.
      RESULTS: Multinomial logistic regression models showed that younger students (6-8
      years) were almost 5 more times more likely to carry heavier schoolbags than
      older students (p < 0.05). Similarly, more girls than boys carried heavier bags,
      and girls were twice more likely to experience fatigue symptoms when carrying
      schoolbags compared with boys (p < 0.05). The mean schoolbag weight was 12.4% of
      the student's body weight and moderately heavier than that reported for other
      countries. CONCLUSIONS: Younger children are in greater need for education about
      schoolbag weight compared with older ones. There is also evidence that girls
      might experience more problems when carrying their schoolbag compared with boys.

PMID- 20142702
TI  - The prevalence, distribution, and effect of pain among adolescents with cerebral
      palsy.
AB  - PURPOSE: : To describe the prevalence, distribution, and intensity of pain and
      determine the relationship between pain intensity and effect on daily activities
      in adolescents with cerebral palsy. METHODS: : A sample of 104 girls and 126
      boys, mean ages 14.7 (SD = 1.7) and 14.8 (SD = 1.7) years, were asked "Have you
      experienced physical pain in the past month?" RESULTS: : Sixty-four percent of
      girls and 50% of boys reported pain. Pain was most frequent in the feet and
      ankles, knees, and lower back of girls and boys at Gross Motor Function
      Classification System levels I to IV. Foot and ankle and knee pain were also
      frequent at level V. The Spearman rho value between intensity and effect on daily
      activities was 0.75 (p < 0.01) and 0.82 (p < 0.01) for girls and boys.
      CONCLUSIONS: : The high prevalence of pain and its effect on daily activities
      suggests a need for greater focus on health promotion.

PMID- 20142703
TI  - Frontal and sagittal plane biomechanics during drop jump landing in boys who are
      obese.
AB  - PURPOSE: To investigate the frontal and sagittal plane lower extremity
      biomechanics during drop jump landings in boys who were obese and boys who were
      of healthy weight. METHODS: Twelve boys participated, 6 were considered as
      healthy weight (body mass index for age <85%, age 11.0 +/- 0.8 years), and 6 were
      considered as obese (body mass index for age >95%, age 12.1 +/- 0.7 years). Three
      dimensional data were collected during landing from a drop jump. Group means were
      compared using Student t tests (alpha = 0.05). RESULTS: Significant differences
      were found in peak hip adduction moment, timing of peak dorsiflexion and knee
      flexion angles, and timing of peak knee extension and abduction moments.
      CONCLUSIONS: Boys who were obese exhibited significant differences in frontal and
      sagittal plane biomechanics when landing from a jump compared with healthy weight
      peers. These differences could place boys who are obese at greater risk for lower
      extremity injuries when they engage in jump-landing activities.

PMID- 20142704
TI  - Measuring function in young children with impairments.
AB  - PURPOSE: To determine the psychometric properties of a new functional assessment
      tool, the WeeFIM 0-3 instrument, intended to measure function in young children
      with physical, cognitive, or developmental impairments from birth to 3 years of
      age. Specific aims were to determine whether differences exist in WeeFIM 0-3
      ratings in children with impairments as compared with those without, controlling
      for age and gender, and to determine the internal consistency, validity, and
      hierarchical properties of the instrument. METHODS: Cross-sectional study of 173
      children with impairments and 354 without impairments. RESULTS: Controlling for
      age, children without impairments had significantly higher mean WeeFIM 0-3
      ratings than children with impairments. There were no differences in mean ratings
      by gender. The instrument displayed high internal consistency, construct, and
      predictive validity; maintained a hierarchy of item difficulty; and discriminant
      properties. CONCLUSION: Further reliability studies are needed to determine the
      instrument sensitivity and ability to detect change over time.

PMID- 20142705
TI  - Measuring function in young children with impairments.

PMID- 20142706
TI  - Motor development toward ambulation in preschool children with myelomeningocele-
      a prospective study.
AB  - PURPOSE: To describe motor development toward ambulation in children with
      myelomeningocele. METHODS: Forty-three children were followed prospectively from
      6 months to 6 years of age. RESULTS: Walking function had been achieved at the 1
      year follow-up in 2 of 38 children, at the 1.5-year follow-up in 7 of 39, at the
      2-year follow-up in 14 of 36, at the 3-year follow-up in 21 of 28, at the 4-year
      follow-up in 28 of 36, and at the 6-year follow-up in 30 of 38. At the 6-year
      follow-up, spasticity was present in 22 of 38 children, 42 of 43 used orthoses,
      and 9 children had not achieved ambulation expected with respect to muscle
      function. CONCLUSIONS: In children with myelomeningocele, walking starts in some
      during the first year of life and is seen increasingly more frequently until 6
      years of age. Motor development before ambulation varies among children with
      similar muscle function. An increased incidence of spasticity is found among
      those not having achieved ambulation with respect to muscle function.

PMID- 20142707
TI  - Treadmill responses and physical activity levels of infants at risk for
      neuromotor delay.
AB  - PURPOSE: This study described developmental changes in treadmill (TM) stepping
      and physical activity (PA) of infants at risk for neuromotor delay (ND) and
      explored these changes by diagnosis of cerebral palsy (CP). Relationships of
      stepping and PA with walking onset were examined. METHOD: Fifteen infants at risk
      for ND (9.9 +/- 2.4 months) were tested every 2 months on a TM until walking
      onset or 24 months of corrected age. We recorded PA profiles using an activity
      monitor. Throughout the study, 6 of the 15 infants received a CP diagnosis.
      RESULTS: Infants increased alternating steps (AltStp), decreased toe contacts,
      and increased high-level PA. Infants with CP showed less AltStp, more toe
      contacts, and less high-level PA than those without CP. Infants' AltStp and high
      level PA revealed a positive correlation to earlier onset of walking. CONCLUSION:
      Future studies should examine whether a TM intervention could improve mobility in
      infants at risk for ND.

PMID- 20142709
TI  - Changes in two children with cerebral palsy after intensive suit therapy: a case
      report.
AB  - PURPOSE: The purpose of this case report was to investigate effects of intensive
      suit therapy on gait, functional skills, caregiver assistance, and gross motor
      ability in children with cerebral palsy. CASE DESCRIPTION: Two children with
      spastic diplegia classified at level III on the Gross Motor Function
      Classification System participated. Outcomes were assessed using dimensions D and
      E of the Gross Motor Function Measure, the Pediatric Evaluation of Disability
      Inventory, and instrumented gait analysis. INTERVENTION: Each child participated
      in the Therasuit Method, 4 hours a day, 5 days a week for 3 weeks. OUTCOMES: Very
      small improvements in function were noted in dimension D of the Gross Motor
      Function Measure and Pediatric Evaluation of Disability Inventory Self-care
      Domain with decreased function in other areas. Improved walking speed, cadence,
      symmetry, joint motion, and posture were found with gait analysis. CONCLUSION:
      Further investigation is needed of the suit itself, and intensive therapy
      programs in children with cerebral palsy.

PMID- 20142710
TI  - Pain in children with cerebral palsy: implications for pediatric physical
      therapy.
AB  - PURPOSE: This literature review explores pain assessment tools and psychosocial
      pain management methods that are pertinent to physical therapy (PT) for children
      with cerebral palsy (CP). SUMMARY OF KEY POINTS: Children with CP experience
      considerable pain that affects quality of life and cooperation during healthcare
      procedures. Physical therapist-led research on interventions to address pain in
      this population is limited, despite evidence for the prevalence of pain during PT
      interventions, and the preponderance of research supporting the use of
      psychosocial pain management during other healthcare-related pain-inducing
      procedures. STATEMENT OF CONCLUSIONS AND RECOMMENDATIONS FOR PHYSICAL THERAPY
      PRACTICE: Research completed primarily by non-physical therapist healthcare
      professionals delineate assessment tools and psychosocial pain management
      techniques that hold promise for evaluating and reducing pain that occurs during
      PT procedures for children with CP.

PMID- 20142708
TI  - Lessons from use of the Pediatric Evaluation of Disability Inventory: where do we
      go from here?
AB  - PURPOSE: The purpose of this article is to review the innovations, applications,
      and effect of the original Pediatric Evaluation of Disability Inventory (PEDI)
      published in 1992 and to describe planned revisions. SUMMARY OF KEY POINTS:
      During the past decade, the PEDI has helped to shift thinking from a
      developmental to a functional focus. Using the PEDI, researchers and clinicians
      worldwide have highlighted variations in functional skill acquisition in clinical
      populations, the importance of recognizing cultural differences, and the value of
      documenting functional progress in relation to interventions. CONCLUSIONS: The
      PEDI has had a rich tradition in helping to document functional development. New
      methods are proposed for the next generation of the PEDI by using item banks and
      computer adaptive testing. RECOMMENDATIONS FOR CLINICAL PRACTICE: The computer
      adaptive testing feature and the revised and expanded content of the new PEDI
      will enable therapists to more efficiently assess children's functioning to a
      broader age group of children.

PMID- 20142712
TI  - Morphologic findings in acute central serous chorioretinopathy using spectral
      domain-optical coherence tomography with simultaneous angiography.

PMID- 20142713
TI  - Correlation of vascular endothelial growth factor with chemokines in the vitreous
      in diabetic retinopathy.
AB  - PURPOSE: The purpose of this study was to simultaneously measure the
      concentrations of multiple cytokines, including vascular endothelial growth
      factor, in the vitreous of patients with diabetic retinopathy and to examine
      their relation with clinical findings. METHODS: Vitreous samples from 46 eyes
      with diabetic retinopathy and 19 eyes with nondiabetic macular disease (controls)
      were used. Nine cytokines were simultaneously measured using a FACSCalibur flow
      cytometer. RESULTS: Vascular endothelial growth factor, interleukin-8, monocyte
      chemotactic protein-1, interferon-inducible protein-10, and monokine induced by
      interferon-gamma were detected in the vitreous samples, and the concentrations
      were significantly (P < 0.001) higher in patients with diabetic retinopathy
      compared with control subjects. Vascular endothelial growth factor, interleukin
      8, monocyte chemotactic protein-1, and monokine induced by interferon-gamma
      concentrations were significantly (P < 0.05) higher in active retinopathy than in
      inactive retinopathy. Furthermore, a significant (P < 0.01) positive correlation
      was observed between vascular endothelial growth factor concentration and
      interleukin-8, monocyte chemotactic protein-1, interferon-inducible protein-10,
      or monokine induced by interferon-gamma concentration in the vitreous.
      CONCLUSION: Vascular endothelial growth factor, interleukin-8, monocyte
      chemotactic protein-1, interferon-inducible protein-10, and monokine induced by
      interferon-gamma were expressed at high levels locally in ocular tissues in
      diabetic retinopathy, and these cytokines may form a network and interact to
      impact the pathogenesis of the disease.

PMID- 20142714
TI  - Injection and suturing technique for scleral fixation foldable lens in the
      vitrectomized eye.

PMID- 20142715
TI  - The Malyugin pupil expander in vitreoretinal surgery.

PMID- 20142716
TI  - Diagnostic and therapeutic challenges. Acute onset panuveitis.

PMID- 20142717
TI  - Enhanced depth imaging spectral-domain optical coherence tomography.

PMID- 20142719
TI  - Re: Verteporfin combination regimens in the treatment of neovascular age-related
      macular degeneration.

PMID- 20142720
TI  - Re: Must screening examinations for retinopathy of prematurity necessarily be
      painful?

PMID- 20142722
TI  - Phase II study of gemcitabine plus docetaxel as second-line treatment in
      malignant pleural mesothelioma: a single institution study.
AB  - OBJECTIVE: The combinations of cisplatin-pemetrexed and cisplatin-gemcitabine are
      considered the standard systemic therapy for malignant pleural mesothelioma
      (MPM), which is a rapidly progressive tumor. The purpose of the present study is
      to evaluate the efficacy, safety, and clinical benefit of the gemcitabine plus
      docetaxel regimen in the second-line treatment of this disease. PATIENTS AND
      METHODS: A total of 37 patients with MPM were treated with the combination of
      docetaxel (80 mg/m) and gemcitabine (1000 mg/m) on day 1 and 14 of a 28-day
      cycle. The regimen was repeated for a maximum of 6 cycles or until disease
      progression or unacceptable toxicity. RESULTS: There was partial response of the
      disease in 7 patients (18.9%), whereas it remained stable in 23 patients (62.2%)
      and progressed in 7 patients (18.9%). The median time to disease progression was
      7 months (range: 5.8-8.2 months) with a mean survival of 16.2 months (range: 13
      19.3 months). CONCLUSION: The biweekly administration of docetaxel and
      gemcitabine, along with granulocyte colony-stimulating factor support,
      constitutes a safe, tolerable, and convenient regimen for the treatment of MPM,
      suggesting that this combination may be a viable option, especially in previously
      treated patients.

PMID- 20142723
TI  - Phase I clinical trial of pegylated liposomal Doxorubicin and docetaxel in
      patients with advanced solid tumors.
AB  - OBJECTIVE: The primary objective of this study was to determine the maximum
      tolerated dose (MTD) of pegylated liposomal doxorubicin (PLD) and docetaxel (T)
      administered in 4 week cycles in patients with advanced solid tumors. PATIENTS
      AND METHODS: Patients were treated with intravenous PLD on day 1 and T on days 1,
      8, and 15. Once the MTD was reached the schedule of PLD was changed to days 1 and
      15 to explore an alternative and potentially more manageable dosing schedule.
      RESULTS: Thirty-two patients were enrolled. A total of 106 cycles (median, 2
      cycles; range, <1-13 cycles) of chemotherapy were administered. Three patients
      experienced dose-limiting toxicities which were stomatitis, anorexia,
      esophagitis, neutropenic fever, fatigue, and muscular weakness. When PLD was
      given on day 1, the MTD was PLD 33 mg/m and T 30 mg/m. MTD was not reached when
      PLD was administered on days 1 and 15: only 1 of 6 patients treated with PLD 20
      mg/m and T 30 mg/m developed dose-limiting toxicities. The most common grade 3 or
      4 hematologic toxicity was grade 3 neutropenia in 5 patients and grade 4 in 5.
      Two patients developed neutropenic fever. The most common grade 3 or 4
      nonhematologic toxicity was grade 3 fatigue in 9 patients and grade 4 in 1. There
      was 1 confirmed PR, 2 unconfirmed PRs, and 12 patients with SD. CONCLUSIONS: This
      combination of PLD and T was found to be feasible and tolerable. The recommended
      dose for phase II studies is PLD 20 mg/m on days 1 and 15 and T 35 mg/m on days
      1, 8, and 15.

PMID- 20142724
TI  - Phase I/II trial of sunitinib plus gefitinib in patients with metastatic renal
      cell carcinoma.
AB  - OBJECTIVES: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor of
      vascular endothelial growth factor and platelet-derived growth factor receptors
      with proven clinical benefit in patients with metastatic renal cell carcinoma
      (RCC). This phase I/II study investigated sunitinib in combination with an
      epidermal growth factor receptor inhibitor, gefitinib, in patients with
      metastatic RCC. METHODS: In phase I, patients received sunitinib 37.5 or 50 mg in
      6-week cycles (4 weeks on treatment, 2 off) plus gefitinib 250 mg, both once
      daily, to determine the sunitinib maximum tolerated dose (MTD). Pharmacokinetics
      was assessed for both drugs. In phase II, patients received sunitinib MTD plus
      gefitinib to evaluate the safety and antitumor activity of this combination.
      RESULTS: Forty-two patients were enrolled: 11 in phase I, and 31 in phase II. In
      phase I, 2 dose-limiting toxicities were observed with sunitinib 50 mg (grade 2
      left ventricular ejection fraction decline and grade 3 fatigue), and 37.5 mg was
      declared the MTD. Thirteen patients treated at the MTD achieved a partial
      response (objective response rate: 37%; 95% confidence interval, 22-55) and 12
      (34%) had stable disease. Median progression-free survival was 11 months (95%
      confidence interval, 6-17). The most commonly reported grade 3/4 treatment
      related adverse event was diarrhea (14%), the only grade 3/4 adverse event to
      occur in >2 patients. Pharmacokinetic analyses did not indicate any drug-drug
      interactions. CONCLUSIONS: In metastatic RCC, sunitinib plus gefitinib
      demonstrated comparable efficacy to sunitinib monotherapy with an acceptable
      safety profile. Dosing, pharmacokinetic profile, and safety support study of
      sunitinib plus an epidermal growth factor receptor inhibitor in other tumor
      types.

PMID- 20142725
TI  - Potential of helical tomotherapy to reduce dose to the ocular structures for
      patients treated for unresectable sinonasal cancer.
AB  - PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans
      generated by segmental multileaf collimator (SMLC) and helical tomotherapy (HT)
      techniques for patients with unresectable sinonasal cancer. METHODS AND
      MATERIALS: SMLC-IMRT and HT-IMRT plans for 5 patients with cancer of the
      paranasal sinuses and nasal cavity were independently optimized using the Eclipse
      treatment planning system (Varian Medial Systems, Palo Alto, CA) and Tomotherapy
      HI-ART treatment planning system (Tomotherapy, Inc, Madison, WI). The goal was to
      deliver a prescribed dose of 70 Gy to at least 95% of the planning target volume
      (PTV) encompassing gross tumor over 35 treatments whereas respecting constraints
      to organs at risk, notably the ocular structures. RESULTS: HT-IMRT reduced the
      maximum doses to the optic chiasm, as well as to the ipsilateral optic nerve and
      retina (P < 0.05, for all). Maximum doses to these structures were reduced by
      10%, 16%, and 14%, respectively, using HT-IMRT compared with SMLC-IMRT.
      Additionally, the mean dose to the ipsilateral lacrimal gland was reduced by 32%
      using HT-IMRT. With respect to conformality, HT-IMRT improved dose homogeneity by
      decreasing "hot-spots." The mean percentage of PTV70 receiving greater than 77 Gy
      (110% of the prescribed dose) was 4.0% for the HT-IMRT plans compared with 17.8%
      for the SMLC-IMRT plans (P = 0.001). CONCLUSIONS: HT-IMRT has the potential to
      improve dose homogeneity to PTVs whereas reducing dose to the optic structures.
      Clinical implications are discussed.

PMID- 20142726
TI  - Phase II study of docetaxel and cisplatin chemotherapy in 5
      fluorouracil/cisplatin pretreated esophageal cancer.
AB  - BACKGROUND: This study was performed to determine the feasibility and safety of
      salvage chemotherapy, using docetaxel and cisplatin in 5-fluorouracil (5-FU) and
      cisplatin-pretreated esophageal cancer. METHODS: Patients with metastatic or
      recurrent esophageal squamous cell carcinoma that had previously been treated
      with 5-FU and cisplatin chemotherapy or chemoradiotherapy were eligible for this
      study. Docetaxel (70 mg/m2) and cisplatin (75 mg/m2) were given as a 1-hour
      intravenous infusion on day 1, and the treatment was repeated every 3 weeks.
      RESULTS: Thirty-eight male patients were enrolled, and 35 patients were available
      for evaluation. The median age was 64.5 years; Eastern Cooperative Oncology Group
      performance status was 0/1/2 = 2/18/18. The median and total numbers of cycles
      delivered were 3.5 (range, 1-9 cycles) and 162, respectively. One patient (2.6%)
      achieved complete response, 12 (31.6%) achieved partial response, 12 (31.6%) had
      stable disease, and 10 (26.3%) had progressive disease. The overall response rate
      was 34.2% (95% confidence interval, 19.6-51.3). The median progression-free
      survival and overall survival times were 4.5 +/- 1.3 months (95% CI, 4.1-4.9) and
      7.4 +/- 0.4 months (95% CI, 7.3-7.5), respectively. The main hematological
      toxicities greater than grade 3 were neutropenia and leucopenia in 20 (52.6%) and
      18 patients (47.3%), respectively. Nonhematological toxicities greater than grade
      3 included asthenia in 12 patients (31.6%), nausea in 7 patients (18.4%), and
      peripheral neuropathy in 6 patients (15.8%). CONCLUSIONS: Chemotherapy with
      docetaxel and cisplatin was an effective and feasible treatment following
      treatment with 5-FU and cisplatin, and would be considered as a salvage option
      for patients with refractory esophageal cancer.

PMID- 20142727
TI  - Irinotecan plus bolus/infusional 5-Fluorouracil and leucovorin in patients with
      pretreated advanced pancreatic carcinoma: a multicenter experience of the Gruppo
      Oncologico Italia Meridionale.
AB  - BACKGROUND: Patients with advanced pancreatic cancer failing gemcitabine-based
      first-line chemotherapy are still in relatively good clinical conditions and may
      still require second-line chemotherapy, which is frequently administered in daily
      clinical practice given to without solid scientific support. PATIENTS AND
      METHODS: A retrospective survey was carried out including 40 patients with stage
      III or IV gemcitabine-refractory pancreatic carcinoma. Patients received standard
      FOLFIRI regimen biweekly until progression or unacceptable toxicity. Response
      evaluation criteria in solid tumors and National Cancer Institute common toxicity
      criteria were employed respectively for response and toxicity assessment.
      RESULTS: Six partial responses (15%) and 14 stabilizations of disease (35%) were
      recorded for a tumor growth control rate of 50%. The median time to progression
      was 3.7 (range, 1-6.5 months), and median overall survival was 6 months (range, 2
      8.2 months). A stabilization of performance status and a subjective improvement
      of cancer-related symptoms were recorded in 21 patients (52.5%). No correlation
      has been found between length of time to progression during first-line
      chemotherapy and length of that reported in the second-line setting or objective
      response. Grade 3-4 diarrhea and mucositis was observed in 15% and 10% of cases,
      respectively. CONCLUSIONS: Data presented in this article demonstrate that the
      second-line FOLFIRI regimen are able to induce an objective response in a
      relatively small fraction of patients with gemcitabine-refractory adenocarcinoma
      of the pancreas. The use of second-line chemotherapy should be carefully proposed
      to patients with good performance status or those who had a good response to
      first-line therapy.

PMID- 20142728
TI  - Early three-dimensional conformal radiotherapy for patients with unresectable
      hepatocellular carcinoma after incomplete transcatheter arterial
      chemoembolization: a prospective evaluation of efficacy and toxicity.
AB  - PURPOSE: We prospectively evaluated the efficacy and toxicity of early 3
      dimensional conformal radiotherapy (3D-CRT) for patients with unresectable
      hepatocellular carcinoma (HCC) after incomplete transcatheter arterial
      chemoembolization (TACE). METHODS: Patients with unresectable HCC who failed 1 or
      2 courses of TACE were eligible for this study. Three dimensional-CRT was added
      for HCC with incomplete uptake of iodized oil. Between January 2006 and February
      2007, 40 patients (43 lesions) were enrolled. TACE was performed by using
      Lipiodol and adriamycin, followed by Gelfoam embolization. Two cycles of TACE
      were performed in 24 patients (60%), whereas 16 patients (40%) underwent one
      cycle. The median dose of 54 Gy (3 Gy daily) was delivered with 3D-CRT. Tumor
      response was evaluated by changes in tumor size on serial computed tomography
      scans and toxicity was evaluated by the Common Terminology Criteria for Adverse
      Events v3.0. RESULTS: An objective response was achieved in 27 of 43 lesions
      (62.8%), with a complete response in 9 lesions (20.9%) and partial response in 18
      lesions (41.9%). The overall survival rate was 72.0% at 1 year and 45.6% at 2
      years. There was no grade 3 or greater acute toxicity. Nine patients (22.5%)
      showed progression of the disease within the irradiated field during the follow
      up and intrahepatic metastases developed in 16 patients (40.0%). CONCLUSION:
      Early 3D-CRT for HCC unresponsive to 1 or 2 cycles of TACE resulted in a 62.8%
      tumor response rate and relatively high complete response rates (20.9%) with
      acceptable toxicity. This study shows that the application of 3D-CRT could be
      considered for patients with incomplete TACE.

PMID- 20142730
TI  - Invasive intraductal papillary mucinous carcinomas of the pancreas: predictors of
      survival and the role of lymph node ratio.
AB  - INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMNs) are being
      increasingly recognized, and often harbor cancer. Lymph node metastases are an
      important prognostic factor for patients with invasive intraductal papillary
      carcinoma (I-IPMC), but the role of lymph node ratio (LNR) in predicting survival
      after surgery for I-IPMC is unknown. METHODS: The combined databases from the
      Surgical Department of Massachusetts General Hospital of Boston and the
      University of Verona were queried. We retrospectively reviewed clinical and
      pathologic data of all patients with resected, pathologically confirmed, I-IPMC
      between 1990 and 2007. Univariate and multivariate analysis were performed.
      RESULTS: I-IPMCs were diagnosed in 104 patients (55 males and 49 females), median
      age was 69 years. Recurrent disease was identified in 49 patients (47.1%) and the
      median 5-year disease specific survival (DSS) was 60.1%. The median number of
      resected/evaluated nodes was 15 (range, 5-60). There were 60 (57.7%) patients who
      had negative lymph nodes (N0), whereas 44 (42.3%) had lymph node metastases (N1).
      Patients with lymph node metastases had a shorter 5-year DSS (28.9%) compared
      with patients with negative lymph nodes (80.3%; P < 0.05) As the LNR increased, 5
      year DSS decreased (LNR = 0, 86.5%; LNR >0 to 0.2, 34.4%; LNR >0.2, 11.1%; P <
      0.05). On multivariate analysis, LNR, the presence of a family history of
      pancreatic cancer and a preoperative value of Ca 19.9 > 37 U/L were significant
      predictors of survival (P < 0.05). CONCLUSIONS: Lymph node ratio is a strong
      predictor of survival after resection for invasive intraductal papillary mucinous
      carcinoma.

PMID- 20142731
TI  - Histopathologic basis for the favorable survival after resection of intraductal
      papillary mucinous neoplasm-associated invasive adenocarcinoma of the pancreas.
AB  - OBJECTIVE: To identify pathologic features that may account for the favorable
      survival after resection of invasive pancreatic adenocarcinoma arising in the
      setting of intraductal papillary mucinous neoplasm (IPMN) compared with standard
      pancreatic ductal adenocarcinoma (PDA) in the absence of IPMN. SUMMARY BACKGROUND
      DATA: The 5-year survival after resection of IPMN-associated invasive
      adenocarcinoma is reported to be between 40% and 60%, which is superior to the 10
      25%, typically cited after resection of standard PDA. It remains unclear whether
      this represents distinct biology or simply a tendency for earlier presentation of
      IPMN-associated invasive adenocarcinoma. METHODS: A single institution's
      prospective pancreatic resection database was retrospectively reviewed to
      identify patients with invasive pancreatic adenocarcinoma who underwent
      pancreatectomy with curative intent. Log rank and Cox regression analysis were
      used to identify factors associated with survival. RESULTS: From 1995 to 2006,
      1260 consecutive patients were identified, 132 (10%) with IPMN-associated
      invasive adenocarcinoma and 1128 (90%) with standard PDA. Actuarial 5-year
      survival was 42% after resection for IPMN-associated versus 19% for standard PDA
      (P < 0.001). However, compared with standard PDA, invasive adenocarcinoma arising
      within an IPMN was associated with a lower incidence of (1) advanced T stage (T2
      T4, 96% vs. 73%, P < 0.001); (2) regional lymph node metastasis (78% vs. 51%, P <
      0.001); (3) poor tumor differentiation (44% vs. 26%, P < 0.001); (4) vascular
      invasion (54% vs. 33%, P < 0.001); (5) perineural invasion (92% vs. 63%, P <
      0.001); and (6) microscopic margin involvement (28% vs. 14%, P < 0.001).
      Specifically, in the presence of any one of the aforementioned adverse pathologic
      characteristics, outcomes after resection for IPMN-associated and standard PDA
      were not significantly different. CONCLUSION: The favorable biologic behavior of
      IPMN-associated compared with standard PDA is based on its lower rate of advanced
      T stage, lymph node metastasis, high tumor grade, positive resection margin,
      perineural, and vascular invasion. In the presence of any one of the
      aforementioned adverse pathologic characteristics, however, survival outcomes
      after resection of IPMN-associated and after resection of standard pancreatic
      adenocarcinoma are similar.

PMID- 20142732
TI  - Randomized controlled trials of surgical interventions.
AB  - BACKGROUND AND OBJECTIVES: Surgical trials pose many methodological challenges
      often not present in trials of medical interventions. If not properly accounted
      for, these challenges may introduce significant biases and threaten the validity
      of the results. METHODS: We systematically reviewed the significance of
      randomized controlled trials in the evaluation of surgical interventions,
      discussed the methodological challenges encountered in designing and conducting
      randomized controlled trials of surgical treatments, and proposed possible
      solutions to overcome these challenges. CONCLUSIONS: Many barriers and issues of
      surgical trials affecting internal validity can be overcome with proper
      methodology, and in most cases these issues do not restrict their conduct.
      Researchers should consider their research question carefully and design a
      surgical trial that contains features appropriate for the question. In doing so,
      they must ensure that the trial is valid, feasible, and affordable--a difficult
      feat, but one well worth the challenge.

PMID- 20142733
TI  - Long-term outcomes for infants with very low risk Wilms tumor treated with
      surgery alone in National Wilms Tumor Study-5.
AB  - OBJECTIVE: To determine the event-free survival (EFS) and overall survival (OS)
      of children with very low risk Wilms tumor (VLRWT) treated with surgery only.
      BACKGROUND: Previous studies suggested that postoperative chemotherapy had not
      improved the prognosis of children with VLRWT. A total of 77 children <24 months
      of age with small (<550 g) Stage I favorable histology Wilms tumors were treated
      with surgery only. This study was closed based on stopping rules to ensure that
      the 2-year EFS was > or =90%. METHODS: A total of 77 children were assessed for
      EFS and OS. Of these patients, 21 enrolled at the time of closure were recalled,
      treated with dactinomycin and vincristine (regimen EE4A), and censored for
      analysis thereafter. About 111 children subsequently treated with EE4A were
      available for comparison. RESULTS: Median follow-up of surviving patients was 8.2
      years for surgery only (range, 1.9-11.8 years) and 5.2 years for the EE4A group
      (range, 1.6-8.9 years). The estimated 5-year EFS for surgery only was 84% (95%
      confidence interval [CI]: 73%, 91%); for the EE4A patients it was 97% (95% CI:
      92%, 99%, P = 0.002). One death was observed in each treatment group. The
      estimated 5-year OS was 98% (95% CI: 87%, 99%) for surgery only and 99% (95% CI:
      94%, 99%) for EE4A (P = 0.70). CONCLUSION: The surgery-only EFS was lower than
      anticipated but, coupled with a much higher than anticipated salvage rate of the
      chemotherapy naive patients whose disease recurred, led to an observed long-term
      OS equivalent to that seen with 2-drug chemotherapy. This approach to the
      treatment of patients with VLRWT eliminates the toxic side-effects of
      chemotherapy for a large majority of patients. A follow-up study is underway to
      confirm these findings.

PMID- 20142734
TI  - Spanish translation and adaptation of Victoria Champion's Health Belief Model
      Scales for breast cancer screening--mammography.
AB  - BACKGROUND: Victoria Champion used the constructs of the Health Belief Model as
      the foundation for developing Champion's Health Belief Scales for Mammography
      Screening (CHBMS). The instrument has been used to collect health beliefs about
      breast screening behaviors among various ethnic populations but has not been
      translated, adapted, or psychometrically evaluated in the Hispanic population.
      OBJECTIVE: The purpose of this article was to report the translation and
      adaptation process from English to Spanish and the psychometric estimates of the
      validity and reliability of CHBMS-Spanish. The original instrument was translated
      from English to Spanish by a professional translator and back-translated into
      English by a focus group of healthcare professionals. METHODS: The tool was given
      to 5 monolingual women to evaluate for content validity, translation validity,
      and cultural appropriateness. A total of 200 self-identified Hispanic women,
      literate in speaking and reading Spanish, aged 45 to 75 years, and without
      history of breast cancer were included in the analyses. RESULTS: The items of the
      scale formed coherent subsets that were relatively independent of each other and
      aligned to the 3 factors prescribed by the Health Belief Model constructs.
      Internal consistency values presented acceptable Cronbach alpha levels ranging
      from .69 to .83. Test-retest reliability correlations were .57 for
      susceptibility, .63 for benefits, and .83 for barriers. CONCLUSION: Overall, the
      Spanish version of CHBMS demonstrated acceptable preliminary values of
      reliability and validity. Further psychometric testing is recommended.
      IMPLICATIONS FOR PRACTICE: The Spanish version of the CHBMS can be used by
      practicing nurses as an instrument to assess health beliefs concerning
      mammography screening among Spanish-speaking Hispanic women.

PMID- 20142735
TI  - Coping with breast cancer: a phenomenological study.
AB  - BACKGROUND: Breast cancer is the most common malignancy affecting women
      worldwide. In Lebanon, a country of 4 million people, breast cancer is also the
      most prevalent type of cancer among Lebanese women. OBJECTIVE: The purpose of
      this study was to gain a more in-depth understanding of the coping strategies
      espoused by Lebanese women with breast cancer. METHODS: The study followed
      purposeful sampling and saturation principles in which 10 female participants
      diagnosed as having breast cancer were interviewed. Data were analyzed following
      a hermeneutical process as described by Diekelmann and Ironside (Encyclopedia of
      Nursing Research. 1998:50-68). RESULTS: Seven main themes and 1 constitutive
      pattern emerged from the study describing the Lebanese women's coping strategies
      with breast cancer. The negative stigma of cancer in the Lebanese culture, the
      role of women in the Lebanese families, and the embedded role of religion in
      Lebanese society are bases of the differences in the coping strategies of
      Lebanese women with breast cancer as compared to women with breast cancer from
      other cultures. CONCLUSION: These findings cannot be directly generalized, but
      they could act as a basis for further research on which to base a development of
      a framework for an approach to care that promotes coping processes in Lebanese
      women living with breast cancer. IMPLICATIONS FOR PRACTICE: Nursing and medical
      staff need to have a better understanding of the individual coping strategies of
      each woman and its impact on the woman's well being; the creation of informal
      support group is indispensable in helping these women cope with their conditions.

PMID- 20142736
TI  - Patient navigation in breast cancer: a systematic review.
AB  - BACKGROUND: The role of the patient navigator in cancer care and specifically in
      breast cancer care has grown to incorporate many titles and functions. OBJECTIVE:
      To better evaluate the outcomes of patient navigation in breast cancer care, a
      comprehensive review of empiric literature detailing the efficacy of breast
      cancer navigation on breast cancer outcomes (screening, diagnosis, treatment, and
      participation in clinical research) was performed. METHODS: Published articles
      were reviewed if published in the scientific literature between January 1990 and
      April 2009. Searches were conducted using PubMed and Ovid databases. Search terms
      included MeSH (Medical Subject Headings) terms, "patient navigator,"
      "navigation," "breast cancer," and "adherence." RESULTS: Data-based literature
      indicates that the role of patient navigation is diverse with multiple roles and
      targeted populations. Navigation across many aspects of the breast cancer disease
      trajectory improves adherence to breast cancer care. The empiric review found
      that navigation interventions have been more commonly applied in breast cancer
      screening and early diagnosis than for adherence to treatment. CONCLUSION: There
      is evidence supporting the role of patient navigation in breast cancer to improve
      many aspects of breast cancer care. IMPLICATIONS FOR PRACTICE: Data describing
      the role of patient navigation in breast cancer will assist in better defining
      future direction for the breast navigation role. Ongoing research will better
      inform issues related to role definition, integration into clinical breast cancer
      care, impact on quality of life, cost-effectiveness, and sustainability.

PMID- 20142737
TI  - Parents' experience of cancer who have young children: a literature review.
AB  - BACKGROUND: The National Cancer Institute estimates that 24% of adults with
      cancer are parenting children younger than 18 years. When a parent is diagnosed
      with cancer, this is a major stressor and often creates multiple problems for
      families. OBJECTIVE: The aim of this article was to conduct a comprehensive
      review of the literature on the experience of parents with cancer who are caring
      for young children. METHODS: A comprehensive review of the literature was
      undertaken using systematic review principles. The search strategy included five
      electronic bibliographic databases, using the search terms: parent, cancer,
      parents and cancer and communication. RESULTS: Thirteen studies were found that
      focused on parents' experience of cancer. Eleven of the 13 studies used solely
      qualitative methodology, and 2 studies used mixed methods. Of the studies
      identified, the majority focused on the experience of mothers, and mainly those
      with a diagnosis of breast cancer. Analysis of the 13 studies on parents'
      experience following a diagnosis of cancer revealed 3 predominant themes: (a)
      being a good parent, (b) telling the children, and (c) maintaining routine at
      home. CONCLUSION: The 3 themes highlight how parents with cancer struggle to know
      how best to talk to their children about cancer and the perceived lack of
      guidance and support from professionals, the feelings of guilt about not being "a
      good parent," and the effort required to maintain routine at home as a way of
      protecting their children. IMPLICATIONS FOR PRACTICE: Support for parents with
      cancer on relevant parenting issues should be acknowledged as an important facet
      of care for oncology nurses, as a mechanism of reducing parental stress and
      psychological distress for the whole family.

PMID- 20142738
TI  - Qualitative study to explore Prospect Theory and message framing and diet and
      cancer prevention-related issues among African American adolescents.
AB  - BACKGROUND: There is a dearth of knowledge regarding factors that may motivate
      African American adolescents to consume healthier diets. OBJECTIVE: To develop
      and test cancer prevention messages based on Prospect Theory on motivation to
      improve dietary intake in African American adolescents and to explore other
      salient factors that may inform dietary intervention design and implementation in
      this population. METHODS: Semistructured in-person qualitative interviews were
      conducted with 13 African American male and female adolescents, aged 12 to 16
      years, in North Carolina. Prospect Theory and message framing were used to guide
      the design of the 4 sets of diet-related messages related to cancer prevention:
      short-term, gain-framed; long-term, gain-framed; short-term, loss-framed; and
      long-term, loss-framed messages. Data were also collected on demographic,
      behavioral, and psychological factors; usual health behaviors; and preferences
      for intervention delivery. RESULTS: Most respondents found the gain-framed, short
      term messages most salient for both fruits/vegetables (8 [61.5%]) and fat
      consumption (7 [53.8%]). For fat consumption only, 2 (15.4%) found the loss
      framed, short-term messages pertinent; none found the loss-framed, long-term
      messages relevant for either dietary variable. All indicated interest in
      participating in a dietary intervention/education program; most preferred the
      Internet as a channel for intervention delivery. Participants expressed diverse
      views regarding knowledge, attitudes, and beliefs regarding healthy eating.
      CONCLUSION: The gain-framed, short-term messages were most salient for motivating
      the majority of respondents to consume a healthy diet and most expressed a strong
      interest in participating in programs about diet and nutrition, with the Internet
      as the preferred communication channel. IMPLICATIONS FOR PRACTICE: Researchers
      conducting dietary interventions and education initiatives and medical
      professionals who counsel African American adolescents should consider using
      Prospect Theory as a theoretical framework, should focus on gain-framed, short
      term messages regarding cancer prevention, and should use the Internet for data
      collection and intervention and information delivery.

PMID- 20142739
TI  - An individualized dyadic problem-solving education intervention for patients and
      family caregivers during allogeneic hematopoietic stem cell transplantation: a
      feasibility study.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) generates
      multiple problems that vary in complexity and create significant distress for
      both patients and their caregivers. Interventions that address patient and family
      caregiver distress during allogeneic hematopoietic stem cell transplantation
      (HSCT) have not been tested. OBJECTIVE: To evaluate the feasibility of conducting
      an individualized dyadic problem-solving education (PSE) intervention during HSCT
      and estimate a preliminary effect size on problem-solving skills and distress.
      METHODS: The PSE intervention consisted of 4 sessions of the Prepared Family
      Caregiver PSE model. Data were collected with an interventionist log, subject
      interviews and standardized questionnaires. RESULTS: Of the 34 adult dyads
      screened, 24 were ineligible primarily because of being non-English-speaking (n =
      11) and inconsistent caregivers (n = 10). Ten dyads (n = 20) were enrolled, and 8
      dyads (n = 16) completed the intervention. Of the 31 sessions, 29 were completed
      (94%). Worsening patient condition was the primary reason for sessions to be
      incomplete. Patients attended 90% of the sessions; caregivers attended 74%.
      Reasons for missed sessions included patient symptom distress and limited
      caregiver availability. Dyads reported being very satisfied (mean, 4.8 [SD, 1.8];
      range, 1-5), stating "an opportunity to talk" and "creative thinking" were most
      beneficial. CONCLUSION: Results suggest that dyads can participate in PSE during
      HSCT and view it as beneficial. Participants identified the active process of
      solving problems as helpful. IMPLICATIONS FOR PRACTICE: Targeted interventions
      that promote effective, meaningful behaviors are needed to guide patients and
      caregivers through HSCT. Future research recommendations include testing a
      version of PSE with fewer sessions, including spousal and nonspousal caregivers
      and those who are non-English speaking.

PMID- 20142740
TI  - Women with lung cancer: quality of life after thoracotomy: a 6-month prospective
      study.
AB  - BACKGROUND: Data about health-related quality of life (QOL) after surgical
      treatment for lung cancer are limited. Such information can be valuable in
      developing appropriate nursing interventions for follow-up care for survivors.
      OBJECTIVES: The purposes of this study were to describe physical and emotional
      QOL of disease-free female non-small cell lung cancer (NSCLC) survivors and to
      determine characteristics associated with greater risk for disruptions. METHODS:
      One-hundred-nineteen women surgically treated for NSCLC completed the Short-Form
      36 (as a measure of physical and mental QOL) along with health status assessments
      (including comorbidity, depression, Center for Epidemiologic Studies-Depression
      Scale, smoking status, and body mass index), dyspnea (Dyspnea Index), meaning of
      illness, and demographic and clinical information at baseline and 3 and 6 months.
      RESULTS: On average, the women were 68 years of age, diagnosed 2 years
      previously, had adenocarcinoma, and were treated surgically with lobectomy. The
      majority (66%) had comorbid disease, 29% had depressed mood (Center for
      Epidemiologic Studies-Depression Scale score > or =16), 8% were current smokers,
      62% were overweight, 22% had dyspnea (scores > or =2), and 24% had a negative
      meaning of illness. Physical and emotional QOL scores were comparable to Short
      Form 36 norms for older adults and exhibited little change over time. Controlling
      for time since diagnosis, dyspnea, and depressed mood were strongly related to
      disruptions in physical and emotional QOL, respectively, across the 6-month study
      period, with comorbid disease contributing to both models. CONCLUSION: Depressed
      mood, comorbidities, and dyspnea were factors related to poorer physical and
      emotional QOL. Survivors with these characteristics might benefit from greater
      supportive care. IMPLICATIONS FOR PRACTICE: Screening for dyspnea, depressed
      mood, and comorbid illness can identify female survivors at-risk for poorer QOL
      after surgery.

PMID- 20142742
TI  - Falls in the community-dwelling elderly with a history of cancer.
AB  - BACKGROUND: Falls place older adults at risk for injuries, resulting in
      functional decline, hospitalization, institutionalization, higher healthcare
      costs, and decreased quality of life. OBJECTIVE: This study examined community
      dwelling elderly to identify if individuals with a history of cancer fall at a
      higher rate than those without cancer, and if the occurrence of falls was
      influenced by individual characteristics, symptoms, or function. METHODS: This
      was a retrospective, cross-sectional study, in 2007, examining 7,448 community
      dwelling elderly 65 years or older in a state in the Midwest. Fallers were
      identified based on a diagnosis of cancer, age, sex, race and ethnicity, poor
      vision, reduced activities of daily living (ADLs), instrumental ADLs, cognition,
      incontinence, pain, or depression. RESULTS: Findings indicated that 2,125 (28.5%)
      had at least 1 fall. Of those who fell, 967 (13.0%) had cancer, and 363 (4.9%)
      with cancer had a fall. CONCLUSION: Predictors of falls in this population
      included race, sex, ADLs, incontinence, depression, and pain, all with P <.05.
      Cancer was not a predictor of falls in this study. IMPLICATIONS FOR PRACTICE:
      This study found a high frequency of falls and suggests a predictive model for
      fall risk in the vulnerable, community-dwelling elderly and will be used to
      inform future studies.

PMID- 20142743
TI  - Health-related quality of life and healthcare experiences in breast cancer
      patients in a study of Swedish women.
AB  - BACKGROUND: Nearly 7,000 women are diagnosed with breast cancer in Sweden every
      year. The primary treatment is surgical and consists mainly of partial or
      modified radical mastectomy followed by adjuvant treatment. The diagnosis and
      treatment may cause distress and decreased health-related quality of life.
      OBJECTIVE: The aim of the present report was to study health-related quality of
      life and satisfaction with hospital stay. METHODS: One hundred women were invited
      to participate in the study, of which 85 accepted. Participants filled in the 36
      item Short-Form Health Survey and a study-specific questionnaire, both
      preoperatively and postoperatively and 6 months after surgery. RESULTS: Women
      with breast cancer experienced an improved health-related quality of life over
      time, but they reported poorer health-related quality of life than the norm value
      after surgery. The lowest scores at all time points were observed on the scales
      role-physical and role-emotional. Patients were very satisfied with the treatment
      and care they had received. Three of 4 women felt that the nursing staff had a
      considerate and conscientious manner, for example, when removing drains.
      CONCLUSION: Diagnosis and treatment of breast cancer have impact on the women's
      health-related quality of life. Measures to meet patients' needs during short
      hospitalization need to be considered. IMPLICATIONS FOR PRACTICE: Nurses must
      ensure that patient's physical and emotional needs are identified and met and
      that appropriate counseling is provided.

PMID- 20142741
TI  - Predictors of depression among older African American cancer patients.
AB  - BACKGROUND: Depression is becoming an increasing concern in cancer patients
      because of its impact on quality of life. Although risk factors of having
      depression have been examined in the literature, there has been no research
      examining these factors in older African American cancer patients. OBJECTIVE:
      This study explores the demographic and illness-related risk factors in older
      African American cancer patients. METHODS: Two hundred eighty-three patients were
      recruited from outpatient oncology clinics. These older African American patients
      completed a questionnaire that included the Geriatric Depression Scale as well as
      sociodemographic characteristics and medical information. chi2 Tests, trend
      tests, and logistic regression were used to identify the demographic and illness
      related factors that predict depression in the sample. RESULTS: The overall
      prevalence of depression in the sample was 27.2%. Younger age (<65 years),
      employment status, proximity to family, and multiple symptoms due to cancer or
      treatment were independent predictors of depression. CONCLUSION: This study
      represents the first attempt to describe the risk factors of depression within
      older African American cancer patients. Findings indicate a high prevalence of
      depression in African American cancer patients which can be attributed to
      identifiable risk factors. IMPLICATIONS FOR PRACTICE: An understanding of the
      risk factors associated with depression can be used to identify those cancer
      patients at risk for depression and initiate early interventions to improve
      psychological outcomes and lessen the potential burden of cancer on these
      patients.

PMID- 20142744
TI  - Patients' views of surgery and surveillance for familial adenomatous polyposis.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is an inherited condition that
      requires prophylactic surgery (colectomy) followed by a lifetime program of
      endoscopic surveillance to prevent colorectal cancer. Patients are normally free
      of symptoms before surgery but a majority report problems related to bowel
      function postoperatively. OBJECTIVE: The aim of the study was to gain a deeper
      understanding of how FAP affects life by exploring patients' view of what it is
      like living with the illness and being committed to a lifelong screening program.
      METHODS: Three focus group interviews were conducted, and data were analyzed
      using descriptive qualitative content analysis. RESULTS: The analysis resulted in
      two categories related to the participants' view of living with FAP. The first
      category was associated with concerns related to the hereditary and lifelong
      nature of the disease as well as to the prophylactic surgery and the second
      category was related to patients' ways of managing life. CONCLUSION: Most
      participants expressed unmet needs, such as lack of healthcare providers with
      good knowledge about FAP, practical and psychosocial support, FAP educational
      programs, and organized meetings with other persons with the condition.
      IMPLICATIONS FOR PRACTICE: One important aspect of living with FAP shared by the
      participants concerned ways of managing life concerns, something that healthcare
      providers caring for patients with FAP should identify and support. Furthermore,
      continuity of care by health care providers with good knowledge about FAP can be
      an important way of reducing patient concerns.

PMID- 20142745
TI  - Facilitated peer support in breast cancer: a pre- and post-program evaluation of
      women's expectations and experiences of a facilitated peer support program.
AB  - BACKGROUND: Peer support programs are associated with the provision of emotional,
      informational, and appraisal support. The benefits of peer support for women with
      breast cancer include reduced social isolation, enhanced coping, and access to
      information. OBJECTIVE: The aim of this study was to conduct a pre- and post
      program evaluation of a 7-week facilitated breast cancer peer support program in
      a cancer support house. METHODS: Women with primary breast cancer (n = 8)
      participated in pre- and post-program focus groups. The interviews were recorded
      and were transcribed verbatim by the researcher. The data were analyzed using
      content analysis. Eight themes were identified. RESULTS: The key themes emerging
      from the pre and post programme focus groups included: The need for mutual
      identification; Post-treatment isolation; Help with moving on; The impact of hair
      loss; Consolidation of information; Enablement/empowerment; The importance of the
      cancer survivor; Mutual sharing. CONCLUSION: It is essential that facilitated
      peer support programs are tailored to meet the support needs of women with breast
      cancer. There is a particular need to facilitate mutual sharing and support for
      hair loss within these programs. IMPLICATIONS FOR PRACTICE: Implications for
      practice emerging from this study include the importance of pre- and post-program
      evaluations in identifying whether peer support programs meet the expectations of
      women with breast cancer, the need for peer/professional programs to support
      women with treatment-induced hair loss, the importance of including cancer
      survivors in support programs, and the need to allow more informal sharing to
      occur in facilitated peer support programs.

PMID- 20142746
TI  - Nurses' perspectives on the care provided to cancer patients.
AB  - BACKGROUND: Optimal care for patients with cancer involves the provision of
      effective physical and psychological care. Nurses are key providers of this care;
      however, the effectiveness of care is dependent on the nurses' training, skills,
      attitudes, and beliefs. OBJECTIVE: The study reported in this article explored
      cancer nurses' perceptions of their ability to provide psychosocial care to
      adults with cancer and their subsequent evaluation of the effectiveness of the
      care provided. This study was the first part of a larger project that evaluated
      the effectiveness of Proctor's model of clinical supervision in an acute care
      oncology environment. METHODS: An exploratory qualitative design was used for
      this study. One focus group interview was conducted with 10 randomly selected
      registered nurses working within the oncology units at a major Melbourne tertiary
      referral hospital. Analytic themes were developed from the coded data using
      content analysis. RESULTS: The 4 analytic themes to emerge from the data were
      frustration, difficult to look after yourself, inadequate communication
      processes, and anger. CONCLUSION: The findings from this study indicate that,
      although informal mechanisms of support are available for oncology nurses, most
      of these services are not accessed. IMPLICATIONS FOR PRACTICE: Leaders in cancer
      care hospital settings need to urgently develop and implement a model of support
      for their oncology nurses who are attempting to provide psychosocial support to
      oncology patients.

PMID- 20142747
TI  - Adaptation of the Information and Support Needs Questionnaire into Turkish to use
      in women with primary relatives with breast cancer.
AB  - BACKGROUND: Breast cancer is the most frequent type of cancer among women in
      Turkey. Because of the high incidence of breast cancer, many women have family
      members who have experienced breast cancer. OBJECTIVE: The aim of this study was
      to test the validity and reliability of the Information and Support Needs
      Questionnaire (ISNQ) for Turkish women, which was originally developed for use in
      women with primary relatives who had breast cancer. METHODS: The study sample
      included 97 women whose primary female relatives had breast cancer. Data were
      collected with a Demographic Questionnaire and the ISNQ. The ISNQ was developed
      by Chalmers et al and was composed of 2 scales: the Importance Scale and the
      Needs Met Scale. RESULTS: Linguistic validity, translation, back translation, and
      content validity were tested with expert opinions. Item-to-total correlation
      scores ranged from 0.22 to 0.72 on the Importance Scale and from 0.23 to 0.60 on
      the Needs Met Scale. Cronbach alpha coefficients were.81 and.83 on the Importance
      Scale and the Needs Met Scale. CONCLUSIONS: The ISNQ, adapted into Turkish, was
      found to have sufficient validity and reliability. IMPLICATIONS FOR PRACTICE: The
      questionnaire can be used to determine information and support needs of women
      whose primary relatives have breast cancer. Nurses and other health professionals
      can conduct interventions directed toward meeting information and support needs
      of women whose primary relatives have breast cancer.

PMID- 20142748
TI  - Improved detection of hepatic metastases from pancreatic cancer using
      periodically rotated overlapping parallel lines with enhanced reconstruction
      (PROPELLER) technique after SPIO administration.
AB  - OBJECTIVES: The purpose of this study was to evaluate the detection of hepatic
      metastases from the pancreatic cancer using different MR imaging methods,
      including superparamagnetic iron oxide (SPIO)-enhanced fat-saturated T2-weighted
      imaging with periodically rotated overlapping parallel lines with enhanced
      reconstruction (PROPELLER) technique. MATERIALS AND METHODS: The institutional
      review board approved this prospective study. Eighty-two patients (mean age, 55
      years) underwent different MR imaging with a 1.5-T scanner. Diagnostic
      performance with receiver operating characteristics (ROC) curves and sensitivity
      were evaluated for the following image sets: (A) unenhanced images (T1-weighted
      in-phase and opposed-phase gradient-echo [GRE] images, and fat-saturated T2
      weighted turbo spin-echo [TSE] images) that were included in the subsequent image
      sets, (B) diffusion-weighted images, (C) SPIO-enhanced fat-saturated T2-weighted
      TSE images with prospective acquisition correction (PACE), (D) SPIO-enhanced T2*
      weighted GRE images, and (E) SPIO-enhanced fat-saturated T2-weighted TSE images
      acquired with PROPELLER and PACE. RESULTS: The areas under the ROC curves were
      0.58 +/- 0.05 (mean +/- standard errors), 0.81 +/- 0.04, 0.70 +/- 0.05, 0.80 +/-
      0.04, and 0.90 +/- 0.03, and sensitivity was 0.47, 0.69, 0.56, 0.66, and 0.77 for
      image sets (A) to (E), respectively, for all lesions. Image set (E) had
      significantly larger area under the ROC curve for detection of hepatic lesions
      and higher sensitivity than others. CONCLUSIONS: SPIO-enhanced fat-saturated T2
      weighted MR imaging with the PROPELLER technique is more effective for detecting
      hepatic metastases of pancreatic cancer than diffusion-weighted MR imaging, SPIO
      enhanced fat-saturated T2WI without the PROPELLER technique, or SPIO-enhanced T2*
      weighted GRE imaging.

PMID- 20142749
TI  - Image fusion in dual energy computed tomography for detection of hypervascular
      liver hepatocellular carcinoma: phantom and preliminary studies.
AB  - OBJECTIVE: This study was designed to determine the optimal blending method and
      parameters to fuse computed tomography (CT) data sets with different energy
      levels in dual-energy CT (DECT) for the detection of hypervascular liver lesions.
      MATERIALS AND METHODS: A liver agar phantom containing 8 conical tubes with
      various concentrations of contrast material, was scanned using a Somatom
      Definition Dual Source CT (DSCT; Siemens, Forchheim, Germany) scanner in the dual
      energy mode at different current settings. CT data sets obtained at voltage
      potentials of 80 kVp and 140 kVp were fused using the linear blending method and
      nonlinear method with different weighting factors (0.1, 0.3, 0.5, 0.7, and 0.9)
      and different parameters sets (A--lambda: 20, omega: 430; B--lambda: 20, omega:
      70; C--lambda: 250, omega: 430; D--lambda: 250, omega: 70). In 20 patients with
      hepatocellular carcinomas, multiphasic liver CT scans including arterial, portal,
      and equilibrium phases were performed. DECT was used only during the arterial
      phase but a voltage potential of 120 kVp was used for both the portal and
      equilibrium phases. For quantitative analyses of the phantom and patient study,
      the contrast-to-noise ratio (CNR) of the lesion to liver on arterial phase
      images, was measured. For qualitative analysis of the CT images of the 20 study
      patients, 5 radiologists, each with a different level of clinical experience,
      independently assessed the 5 types of image sets regarding lesion conspicuity and
      overall image quality. This study followed the guidelines of our hospital's
      institutional review board, and patient informed written consent was not
      required. Statistical comparisons were made using repeated measures ANOVA with
      Bonferroni correction for multiple comparisons. RESULTS: For the phantom and
      patient studies, 2 linear images with weighting factors 0.5 and 0.7 and 2
      nonlinear images with a wide width, showed a higher CNR of hyperattenuated
      lesions than a standard 0.3 weighting factor linear blended image (P < 0.05). For
      the patient study, a weighting factor 0.5 and a 0.7 linear mixing image had a
      9.2% and an 11.8% increase in CNR, respectively, more than a 0.3 linear blended
      image (P < 0.05). Moreover, a nonlinear mixing image with parameters A and C had
      a 14.0% increase in CNR over that of a 0.3 linear blended image (P < 0.05). In a
      qualitative study performed by the 5 reviewers, the nonlinear blended image set
      with a low level and wide width, was estimated as the most preferred image set
      (55%-100%), whereas a weighting factor of a 0.3 linear blended image was
      determined as the least preferred image (65%-100%). CONCLUSIONS: Linear blended
      images with a higher weighting factor than 0.5 and nonlinear blended images with
      a wide width are able to provide improved lesion-to-liver CNR over the standard
      linear blending method (with a weighting factor of 0.3). Furthermore, the linear
      blending method with a low level and a high width provided the most preferred
      image set for hypervascular hepatocellular carcinoma detection by our
      radiologists.

PMID- 20142750
TI  - In untreated HIV-1-infected children, PBMC-associated HIV DNA levels and cell
      free HIV RNA levels are correlated to distinct T-lymphocyte populations.
AB  - BACKGROUND: Clinical studies support biologically independent roles of cell-free
      HIV particles and HIV-infected cells in disease progression. The associations
      between the level of infected cells and immune markers have been poorly studied,
      particularly in perinatally infected children. OBJECTIVE: We tested the
      hypothesis that independent roles of cell-free virus and infected cells in HIV
      pathogenesis should be revealed by different associations between each of them
      and specific immune markers. METHODS: Levels of HIV RNA and DNA, HIV-specific CD8
      T lymphocytes, activated and naive/memory T lymphocytes were determined in 44
      untreated HIV-1-infected children. Pearson partial correlation coefficients were
      used to assess associations between the variables. RESULTS: Here we provide new
      information, by showing a direct correlation between the percentages of CD4HLA-DR
      lymphocytes and HIV DNA levels. Furthermore, higher HIV-specific CD8 T-lymphocyte
      frequencies were associated with lower HIV DNA levels. In contrast, CD838
      lymphocytes and memory CD4 lymphocytes were correlated only to the HIV RNA level.
      All correlations were independent of age and CD4 depletion. CONCLUSIONS: Several
      immune markers were correlated to either the HIV RNA or the HIV DNA level, but
      never to both of them, supporting the concept that cell-free virus and infected
      cells play different roles in HIV-1 immunopathogenesis.

PMID- 20142751
TI  - Sexual dysfunction in women with cardiovascular disease: what do we know?
AB  - The problem of sexual dysfunction in cardiovascular disease has received
      attention in both professional and lay literature, particularly for men. There is
      only beginning awareness of the problem of sexual dysfunction in women in general
      and for those with cardiovascular disease. This evidence-based review focuses on
      the problem of sexual dysfunction in women in the general population compared
      with those women with cardiovascular disease. The underlying mechanisms of female
      sexual dysfunction are addressed, along with what is known about female sexual
      dysfunction in those with coronary artery disease, hypertension, and heart
      failure. The assessment and management of female sexual dysfunction in the
      presence of cardiovascular disease are addressed, although the strategies for
      management are controversial and evidence is lacking in some cases. Nurses can
      play a key role in initiating discussion with women related to sexual dysfunction
      and assisting them in finding appropriate resources and treatment.

PMID- 20142752
TI  - Time to treatment for acute coronary syndromes: the cost of indecision.
AB  - BACKGROUND AND RESEARCH OBJECTIVES: : Multiple sociodemographic and environmental
      factors have been associated with urgent treatment-seeking behaviors for patients
      experiencing acute coronary syndromes (ACSs). However, variables that directly
      affect the decision to seek care in the emergency department (ED) have been less
      well defined. The objective of this study was to explore the factors associated
      with a decision to seek care for symptoms of ACSs and to describe patient
      characteristics associated with time to presentation. SUBJECTS AND METHODS: : A
      cross-sectional, descriptive design was used. The nonprobability sample included
      256 patients admitted to the hospital with ACSs. The study was conducted on
      cardiac step-down units at 2 large urban medical centers. Reasons for seeking
      care were elicited during structured interviews in the patient's room. These
      factors and other patient characteristics were treated as predictor variables in
      an analysis of time from symptom onset to arrival in the ED. RESULTS AND
      CONCLUSIONS: : Five categories of decision making were identified through
      descriptive content analyses and were labeled new onset of chest pain, ongoing
      evaluation of symptom severity, symptoms other than chest pain that worsened or
      were unrelieved, externally motivated, and internally motivated. Median time from
      symptom onset to arrival in the ED was 9.5 hours for women and 6 hours for men.
      Patients who experienced constant pain (hazard ratio, 1.44; P =.01) and those
      with ST-segment elevation myocardial infarction (hazard ratio, 1.59; P = .004)
      sought treatment significantly sooner than patients with intermittent pain. Older
      patients sought treatment later (hazard ratio, 0.99; P = .02). Patients who are
      older and experience intermittent pain should be encouraged to seek emergent
      treatment for symptoms that may represent ACSs. New evidence of patients'
      decision-making processes and dangerous delay in time to treatment provides
      knowledge needed to counsel patients about the benefits of seeking care quickly
      when symptoms begin.

PMID- 20142753
TI  - High-density lipoprotein, apolipoprotein AI concentrations, and celiac disease.

PMID- 20142754
TI  - Treatment of bleeding ulcer.

PMID- 20142755
TI  - Long-term prognosis of combined hepatocellular and cholangiocarcinoma after
      curative resection comparison with hepatocellular carcinoma and
      cholangiocarcinoma.
AB  - GOAL: In this study, we attempted to evaluate the prognosis of combined
      hepatocellular and cholangiocarcinoma (cHCC-CC) with comparison to hepatocellular
      carcinoma (HCC) and intrahepatic cholangiocarcinoma (CC). BACKGROUND: The
      prognosis of cHCC-CC has not been fully elucidated. In this study, we attempted
      to evaluate the prognosis of cHCC-CC with comparison to HCC and CC. STUDY:
      Consecutive patients who underwent curative resection for cHCC-CC at a single
      tertiary care center in Korea and their age, sex, and Child-Turcotte-Pugh class
      matched HCC and CC patients were included. We evaluated time-to-recurrence (TTR)
      and overall survival (OS) of cHCC-CC cases and compared them with HCC and CC
      patients. RESULTS: Thirty cHCC-CC, 60 HCC, and 60 CC patients were included. For
      cHCC-CC group, the median TTR and OS were 5.4 and 18.0 months. After adjustment
      for confounding factors, the cHCC-CC group had a shorter TTR than did HCC group
      [relative risk (RR), 2.76; P<0.001] and CC group (RR, 2.00; P=0.013), and a
      shorter OS than HCC group (RR, 4.70; P<0.001). Compared with the each stage I
      diseases, cHCC-CC had shorter TTR than HCC (RR, 4.59; P=0.001) and CC (RR, 2.74,
      P=0.015) and shorter OS than HCC (RR, 9.35; P=0.001). CONCLUSIONS: The results of
      this study indicated that cHCC-CC had a significantly poorer prognosis than HCC
      and CC even after curative resection.

PMID- 20142756
TI  - Effect of preoperative biliary drainage on coagulation and fibrinolysis in severe
      obstructive cholestasis.
AB  - GOALS: To evaluate the function of coagulation and fibrinolysis in cholestatic
      patients before and after preoperative biliary drainage (PBD). BACKGROUND:
      Cholestasis owing to an obstructive biliary malignancy is associated with
      postoperative complications related to a proinflammatory state, an impaired
      hepatic synthesis function, and a potential derangement of hemostasis. Hence, PBD
      is advocated for cholestatic patients undergoing major surgery. STUDY: Plasma
      coagulation and fibrinolytic parameters were assessed in 24 cholestatic patients
      and 10 controls. In 9 cholestatic patients, the parameters were reassessed at
      least 4 weeks after PBD. RESULTS: Compared with controls, cholestatic patients
      showed lower concentrations (P<0.001) of plasma vitamin K-dependent factors II
      and VII, whereas prothrombin time, activated partial thromboplastin time, and
      factor V were unaltered. Thrombin generation was increased in cholestatic
      patients, as reflected by higher plasma concentrations of thrombin-antithrombin
      complexes and D-dimers. Fibrinolysis was significantly impaired as evidenced by
      low plasminogen activator activity (PAA) owing to an increase in plasminogen
      activator inhibitor -1). Elevated markers for thrombin generation thrombin
      antithrombin decreased after PBD from 10.7+/-1.2 to 5.7+/-0.7 ng/mL (P<0.05).
      Additionally, impairment of fibrinolysis in cholestatic patients resolved after
      PBD (plasminogen activator inhibitor-1 levels decreased from 19+/-1 to 10+/-1
      IU/mL and plasminogen activator activity increased from 82+/-3 to 110+/-4%,
      respectively). D-dimers remained unaltered after PBD, likely because of
      normalization of coagulation and fibrinolytic activity. CONCLUSIONS: Obstructive
      cholestasis is associated with a procoagulant state, despite an impaired vitamin
      K-dependent coagulation factor synthesis. Virtually all alterations in
      coagulation and fibrinolysis were reversed by biliary drainage.

PMID- 20142757
TI  - Pseudocyst management: endoscopic drainage and other emerging techniques.
AB  - Pseudocyst formation is a well known complication of pancreatitis. Not all
      pancreatic pseudocysts require intervention. Selected patients who are
      asymptomatic can be subject to expectant management. Spontaneous resolution has
      been shown to occur in 40% to 50% of patients with no serious complications
      occurring during the observation period. Intervention is warranted if the patient
      is symptomatic, there is a progressive increase in size or if the pseudocyst is
      infected. Surgery was the only available treatment for pseudocysts for a long
      time. Of late other modalities like percutaneous, endoscopic, and laparoscopic
      drainage have come to be seen as viable alternatives.

PMID- 20142758
TI  - Reliability and diagnostic characteristics of the JFK coma recovery scale
      revised: exploring the influence of rater's level of experience.
AB  - OBJECTIVE: To confirm the reliability and diagnostic validity of the JFK Coma
      Recovery Scale-Revised (CRS-R) across raters with varying levels of experience.
      METHODS: Thirty-one patients with disorders of consciousness were recruited from
      6 Norwegian hospitals. MAIN OUTCOME MEASURES: CRS-R and the Disability Rating
      Scale. RESULTS: Reliability measures were good for the CRS-R total scores and
      moderate to good for its subscales. Diagnostic agreement among examiners was
      good. Raters' experience with the CRS-R favorably influenced reliability.
      Sensitivity and specificity analyses demonstrated better detection of patients in
      minimally conscious state on the CRS-R relative to the Disability Rating Scale.
      CONCLUSIONS: The CRS-R is a reliable tool for diagnosing vegetative state and
      minimally conscious state. Raters' level of experience influences the reliability
      of the CRS-R scores.

PMID- 20142759
TI  - Spatiotemporal deficits and kinematic classification of gait following a
      traumatic brain injury: a systematic review.
AB  - OBJECTIVE: To identify the key biomechanical gait abnormalities resulting from
      traumatic brain injury (TBI) and determine whether the abnormalities support a
      system for the classification of gait disorders. DESIGN: Systematic review with
      data from quantitative studies synthesized in a narrative format. PARTICIPANTS:
      Adults with TBI. OUTCOME MEASURES: Spatiotemporal, kinematic, and kinetic
      parameters of classification systems. RESULTS: The search identified 38 articles
      that reported on various methods for gait assessment in TBI. Three-dimensional
      gait analysis (3DGA) was used in 15 studies, primarily to quantify spatiotemporal
      parameters. Results revealed that people with a TBI walked more slowly with
      shorter steps and greater mediolateral sway following TBI. Stepping over
      obstacles, walking with eyes closed, or performing dual tasks accentuated gait
      deficits. Only one small study reported kinematic data for the major lower limb
      joints in 8 well recovered patients. One further study used 3DGA to classify the
      gait patterns of people with TBI but this classification was based on methods
      developed for stroke and cerebral palsy. No studies attempted to develop a
      classification system on the basis of the gait disorders of people with TBI.
      CONCLUSION: Although the studies were generally of high quality, little is known
      about the nature of gait disorders following TBI. Classification based on
      systematic description of gait disorders following TBI has not been attempted.

PMID- 20142760
TI  - Erythropoietin is neuroprotective in a preterm ovine model of endotoxin-induced
      brain injury.
AB  - Intrauterine infection and inflammation have been linked to preterm birth and
      brain damage. We hypothesized that recombinant human erythropoietin (rhEPO) would
      ameliorate brain damage in anovine model of fetal inflammation. At 107 +/- 1 day
      of gestational age (DGA), chronically catheterized fetal sheep received on 3
      consecutive days 1) an intravenous bolus dose of lipopolysaccharide ([LPS]
      approximately 0.9 microg/kg; n = 8); 2) an intravenous bolus dose of LPS,
      followed at 1 hour by 5,000 IU/kg of rhEPO (LPS + rhEPO, n = 8); or 3) rhEPO (n =
      5). Untreated fetuses (n = 8) served as controls. Fetal physiological parameters
      were monitored, and fetal brains and optic nerves were histologically examined at
      116 +/- 1 DGA. Exposure to LPS, but not to rhEPO alone or saline, resulted in
      fetal hypoxemia, hypotension (p < 0.05), brain damage, including white matter
      injury, and reductions in numbers of myelinating oligodendrocytes in the
      corticospinal tract and myelinated axons in the optic nerve (p < 0.05 for both).
      Treatment of LPS-exposed fetuses with rhEPO did not alter the physiological
      effects of LPS but reduced brain injury and was beneficial to myelination in the
      corticospinal tract and the optic nerve. This is the first study in a long
      gestation species to demonstrate the neuroprotective potential of rhEPO in
      reducing fetal brain and optic nerve injury after LPS exposure.

PMID- 20142761
TI  - Aldose reductase deficiency improves Wallerian degeneration and nerve
      regeneration in diabetic thy1-YFP mice.
AB  - This study examined the role of aldose reductase (AR) in diabetes-associated
      impaired nerve regeneration using thy1-YFP (YFP) mice. Sciatic nerves of
      nondiabetic and streptozotocin-induced diabetic AR(+/+)YFP and AR(-/-)YFP mice
      were transected after 4 weeks of diabetes. Wallerian degeneration and nerve
      regeneration were evaluated at 1 and 2 weeks postaxotomy by fluorescence
      microscopy. Motor nerve conduction velocity recovery and regenerating nerve
      morphometric parameters were determined at 10 and 20 weeks, respectively. There
      was no difference in the extent of Wallerian degeneration, size of regenerating
      stump, motor nerve conduction velocity recovery, or caliber of regenerating
      fibers between nondiabetic AR(+/+)YFP and AR(-/-)YFP mice. In diabetic AR(+/+)YFP
      mice, Wallerian degeneration was delayed, associated with slower macrophage
      invasion and abnormal vascularization. Those mice had smaller regenerating
      stumps, slower motor nerve conduction velocity, and smaller regenerating fibers
      compared with nondiabetic mice. These features of impaired nerve regeneration
      were largely attenuated in diabetic AR(-/-)YFP mice. Retarded macrophage invasion
      and vascularization associated with Wallerian degeneration were normalized in
      diabetic AR(-/-)YFP mice. These results indicate that AR plays an important role
      in diabetes-associated impaired nerve regeneration, in part by affecting
      vascularization and macrophage invasion during Wallerian degeneration. The thy1
      YFP mice are valuable tools for further investigation of the mechanism of
      diabetes-associated nerve regeneration.

PMID- 20142762
TI  - Motor axonal sprouting and neuromuscular junction loss in an animal model of
      Charcot-Marie-Tooth disease.
AB  - Muscle weakness in Charcot-Marie-Tooth Type 1A disease (CMT1A) caused by
      mutations in peripheral myelin protein 22 (PMP22) has been attributed to an
      axonopathy that results in denervation and muscle atrophy. The underlying
      pathophysiological mechanisms involved are not understood. We investigated motor
      performance, neuromuscular junctions (NMJs), physiological parameters, and muscle
      morphometry of PMP22 transgenic mice. Neuromuscular junctions were progressively
      lost in hindlimb muscles of PMP22 transgenic mice, but their motor performance
      did not completely deteriorate during the observation period. There was
      considerable variability, including in laterality, in deficits among the animals.
      Cross-sectional areas and mean fiber size measurements indicated variable
      myofiber atrophy in hindlimb muscles. There was substantial concomitant axonal
      sprouting, and loss of neuromuscular junctions was inversely correlated with the
      accumulated length of axonal branches. Synaptic transmission studied in isolated
      nerve/muscle preparations indicated variable partial muscle denervation.
      Acetylcholine sensitivity was higher in the mutant muscles, and maximum tetanic
      force evoked by direct or indirect stimulation, specific force, and wet weights
      were markedly reduced in some mutant muscles. In summary, there is partial muscle
      denervation, and axons may retain some regenerative capacity but fail to
      reinnervate muscles in PMP22 transgenic mice.

PMID- 20142763
TI  - Loss of neuronal protein expression in mouse hippocampus after irradiation.
AB  - The effects of radiation on neurons are incompletely characterized. We evaluated
      changes in the expression of neuronal nuclear and other proteins in the mouse
      hippocampus after 17-Gy whole-brain irradiation. Expression of neuronal nuclei
      (NeuN), neuron-specific enolas, prospero-related homeobox 1 (Prox1), calbindin
      D28k, and synaptophysin 1 in the CA1, CA3, and dentate gyrus of the hippocampus
      was determined by immunohistochemistry; neuronal numbers were estimated by design
      based stereology. At 7 days after irradiation, there was a marked reduction of
      NeuN neurons in CA3. Stereologic estimates confirmed a significant reduction in
      NeuN neurons in CA3 at 7 days, in the dentate gyrus at 7 days, 3 weeks and 2
      months, and in CA1 at 2 months compared with controls; neuron-specific enolase
      and prospero-related homeobox 1-positive neurons in the CA3 subregion were also
      decreased at 7 days. The numbers of granule and pyramidal cells identified by 4'6
      diamidino-2-phenylindole nuclear staining, however, remained unchanged, and there
      were no changes in calbindin D28k or synaptophysin 1 immunoreactivity after
      irradiation. We conclude that irradiation may result in a temporary loss of
      neuronal protein expression in mouse hippocampus. These changes do not
      necessarily indicate loss of neurons and indicate the need for caution regarding
      the use of phenotypic markers such as NeuN to estimate changes in neuronal
      numbers after irradiation.

PMID- 20142764
TI  - "Hairy baskets" associated with degenerative Purkinje cell changes in essential
      tremor.
AB  - Essential tremor (ET) is one of the most common neurologic diseases. Increased
      numbers of torpedoes and Purkinje cell (PC) loss have been documented in the
      brains of patients with ET. We recently observed a dense and tangled appearance
      ("hairiness") of the basket cell axonal plexuses that surround PC soma in
      Bielschowsky preparations of cerebellar cortex in ET brains. Here, we assessed
      basket cell "hairiness" in 37 ET (32 cerebellar ET; 5 Lewy body variant ET), 21
      nondisease control, and 48 disease control brains using a semiquantitative scale.
      In 8 cerebellar ET cases (25%), there were high basket scores (rating = 3),
      whereas no Lewy body variant ET, 1 nondisease control (4.8%), and 2 diseased
      controls (4.2%) had high basket scores (p = 0.001). The hairy basket scores
      correlated with numbers of torpedoes (p < 0.001) and inversely with numbers of
      PCs (p = 0.06). Axonal plexus density obtained by image analysis of basket cell
      processes traced from digitized images was higher in ET than in nondiseased
      control cases (p = 0.016). Closely spaced sites of synaptic contact between
      basket cell processes and PCs were identified by electron microscopy in ET cases.
      These data indicate that structural changes are not restricted to PCs in ET, and
      that other neurons within their functional network may be involved in its
      pathogenesis.

PMID- 20142766
TI  - Brody disease: insights into biochemical features of SERCA1 and identification of
      a novel mutation.
AB  - Brody disease is an inherited disorder of skeletal muscle function characterized
      by increasing impairment of relaxation during exercise. The autosomal recessive
      form can be caused by mutations in the ATP2A1 gene, which encodes for the
      sarcoplasmic/endoplasmic reticulum Ca-ATPase 1 (SERCA1) protein. We studied 2
      siblings affected by Brody disease. The patients complained of exercise-induced
      delay of muscle relaxation and stiffness since childhood and had gene analysis of
      ATP2A1. Morphologic and biochemical studies were performed on a muscle biopsy
      from 1 patient. The biopsy showed fiber size variation and increased numbers of
      fibers with internal nuclei. Ultrastructural examination revealed dilatation of
      lateral cisternae and proliferation of tubular elements of the sarcoplasmic
      reticulum. By immunohistochemistry, SERCA1 was expressed in a normal pattern, but
      sarcoplasmic reticulum Ca-ATPase activity was significantly reduced.
      Immunoblotting after high-resolution 2-dimensional gel electrophoresis showed a
      significant difference in the amount of SERCA1 protein between the patient and
      controls. Both patients were found to have 2 previously unreported in-frame
      deletions in ATP2A1. Because SERCA1 protein has specific biochemical
      characteristics in our patient, these results underline the importance of a
      pathologic and biochemical analyses for the diagnosis. In addition, we describe 2
      novel mutations in the ATP2A1 gene.

PMID- 20142765
TI  - Genetic ablation of luteinizing hormone receptor improves the amyloid pathology
      in a mouse model of Alzheimer disease.
AB  - Amyloid-beta peptide (Abeta) plays an essential pathophysiologic role in
      Alzheimer disease, and elevation of luteinizing hormone (LH) levels during aging
      has been implicated in its pathogenesis. To assess the effect of LH receptor
      deficiency on Abeta accumulation, we generated a bigenic mouse model,
      APPsw(+)/Lhr(-/-), which expresses human amyloid precursor protein (APPsw) in the
      background of LH receptor (Lhr) knockout. Genetic ablation of Lhr resulted in a
      significant decrease in the number of Abeta plaques and protein content in the
      hippocampus and cerebral cortex in both male and female mice. Accordingly,
      several Abeta deposition-related neuropathologic features and functionally
      relevant molecules were markedly improved, including decreased astrogliosis,
      reductions of elevated phosphorylated tau, c-fos, alpha7-nicotinic acetylcholine
      receptor, and restoration of the altered neuropeptide Y receptors Y1 and Y2.
      Diminution of Abeta accumulation in the absence of LH receptor supports the
      contention that dysregulation of LH may impact the pathogenesis of Alzheimer
      disease. The APPsw(+)/Lhr(-/-) mouse may be a useful tool for advancing
      understanding of the role of LH-mediated events in Alzheimer disease and a model
      in which to test therapeutic interventions.

PMID- 20142767
TI  - Synaptophysin immunoreactivity in the human hippocampus and neocortex from 6 to
      41 weeks of gestation.
AB  - To assess the synaptic vesicle protein synaptophysin as a potential marker for
      maturation in the human fetal brain, synaptophysin immunoreactivity (sIR) was
      prospectively studied in postmortem sections of 162 normal human fetal and
      neonatal brains of both sexes from 6 to 41 weeks' gestational age. There was a
      consistent temporal and spatial pattern of sIR in the hippocampus and cerebral
      neocortex. In the rostral hippocampus, sIR was first apparent in the molecular
      zone of the dentate gyrus at 12 weeks, followed by CA2 at 14 weeks, CA3 and CA4
      at 15 to 16 weeks, and CA1 at 19 weeks; it was incomplete until 26 weeks. In
      frontal neocortex, sIR developed in a laminar pattern above and below the
      cortical plate as early as 12 weeks, around Cajal-Retzius neurons of the
      molecular zone at 14 weeks, surrounding pyramidal neurons of Layers 5 and 6 at 16
      weeks, and at the surface of neuronal somata in Layers 2 and 4 at 22 weeks. At 33
      weeks, Layers 2 and 4 still had less sIR than other layers. Uniform sIR among all
      cortical layers was evident at 38 weeks. Ascending probable thalamocortical axons
      were reactive as early as 12 weeks and were best demonstrated by 26 weeks, after
      which increasing sIR in the neuropil diminished the contrast. The sIR was
      preserved for more than 96 hours postmortem, even in severely autolytic brains.
      We conclude that synaptophysin is a reliable marker in human fetal brain and that
      sIR provides the means for objective assessment of cerebral maturation in normal
      brains and to enable interpretation of abnormal synaptic patterns in pathological
      conditions.

PMID- 20142768
TI  - Adenoviral gene delivery of pigment epithelium-derived factor protects striatal
      neurons from quinolinic acid-induced excitotoxicity.
AB  - The 50-kDa secreted glycoprotein pigment epithelium-derived factor (PEDF) is
      neuroprotective for various types of cultured neurons, but whether it is
      neuroprotective for neurons in vivo is not known. We examined the effects of
      adenovirus-mediated gene transfer of PEDF on quinolinic acid (QA)-induced
      neurotoxicity in rats. Adenoviral vector containing the human PEDF gene (Ad.PEDF)
      or Escherichia coli beta-galactosidase gene (Ad.LacZ) was directly injected into
      the right striatum 7 days before the injection of QA. Immunohistochemical
      analysis using antibodies specific for the neuronal markers dopamine and cyclic
      adenosine monophosphate-regulated phosphoprotein of 32 kDa, neuronal nuclei, and
      choline acetyltransferase revealed that the QA-induced striatal damage was
      significantly reduced in Ad.PEDF-treated rats. Overexpression of PEDF also
      reduced the expression of the inflammation-related genes for interleukin 1beta,
      tumor necrosis factor alpha, and macrophage inflammatory protein 1alpha 1 day
      after QA injection. Deletion analysis of human PEDF protein demonstrated that
      overexpression of PEDFDelta44-121 failed to protect neurons against QA-induced
      excitotoxicity, whereas PEDFDelta78-121 retained the neuroprotective activity,
      suggesting that amino acid residues 44-77 of the PEDF sequence are essential for
      PEDF-mediated neuroprotection in vivo. These results provide the first evidence
      that PEDF and its deletion mutant PEDFDelta78-121 are effective in protecting CNS
      neurons against excitotoxicity in vivo.

PMID- 20142769
TI  - Matrix metalloproteinase-19 is highly expressed in astroglial tumors and promotes
      invasion of glioma cells.
AB  - Glial tumors exhibit a high morbidity and mortality because of their invasive
      nature. Matrix metalloproteinase 19 (MMP19) is a secreted protease that together
      with epilysin (MMP28) forms a structural subgroup of MMPs. We analyzed their
      expression by quantitative reverse transcription polymerase chain reaction,
      Western blot, and immunohistochemistry in tumor and normal control brain tissues
      and in glioblastoma (GB) cells and performed MMP19 silencing functional assays.
      Matrix metalloproteinase 28 was transcribed to the same extent in normal brain
      samples and gliomas but was undetectable in GB cell lines. In contrast, MMP19 was
      detected by immunohistochemistry in normal brain samples only in endothelial
      cells but was found at high levels in astrocytomas of different World Health
      Organization grades in situ and in GB cells in vitro. Matrix metalloproteinase 19
      was upregulated in GB cells after exposure to proinflammatory cytokines. In
      Transwell invasion assays, MMP19-silenced cells migrated more slowly through
      laminin-, basal lamina-, and brevican-coated membranes than controls. Matrix
      metalloproteinase 19-silenced GB cells also migrated into brain tissue slices
      compared with control cells. Brevican, a brain-specific proteoglycan and major
      component of brain extracellular matrix, was degraded by recombinant human MMP19.
      Taken together, these results indicate that MMP19 is highly expressed in
      proliferating astrocytoma/glioma cells, and that its expression may facilitate
      their invasion through brain extracellular matrix components.

PMID- 20142770
TI  - Self-selection effects in smokers attending lung cancer screening: a 9.5-year
      population-based cohort study in Varese, Italy.
AB  - BACKGROUND: We hypothesize that mortality risk profile of participants and
      nonparticipants in nonrandomized lung cancer (LC) screening of smokers may be
      different. METHODS: In 1997, a population-based cohort of 5815 smokers of Varese
      Province was invited to nonrandomized LC screening by annual chest x-ray
      examination for 4 years. LC risk factors and screening participation rate were
      recorded. Except for screening, the whole cohort received usual care. After 9.5
      year observation, we compared mortality of participants versus nonparticipants by
      assessing age-standardized all-cause mortality rate ratio (MRR) and disease group
      specific MRR with 95% confidence intervals (95% CI). RESULTS: Self-selected
      screening participants were 21% of cohort. Participants were younger (p < 0.001),
      were more frequently current smokers (p = 0.019), had more pack-years of smoking
      (p < 0.0001), and had higher rate of LC family history (p < 0.0001) and of
      occupational LC risk (p < 0.0001) relative to nonparticipants. In logistic
      regression analysis familial LC, occupational risk and pack-years smoked were
      significant predictors of participation in screening and of developing LC.
      Participants displayed a healthy effect, as shown by all-cause MRR = 0.67 (95%
      CI, 0.53-0.84), all cancers except LC MRR = 0.61 (95% CI, 0.41-0.91),
      cardiovascular diseases MRR = 0.38 (95% CI, 0.22-0.63), and noncancer disease
      other than cardiovascular or respiratory MRR = 0.57 (95% CI, 0.34-0.92). The LC
      mortality (MRR = 1.40; 95% CI, 1.03-1.91) was higher in participants relative to
      nonparticipants (p = 0.031). CONCLUSION: The selection effect in LC screening
      participants was dual: healthy effect and higher LC mortality. In assessing the
      overall effectiveness of LC screening on a population level, a higher LC
      mortality risk in participants should be considered.

PMID- 20142771
TI  - Motor unit number estimates in masters runners: use it or lose it?
AB  - INTRODUCTION: A contributing factor to the loss of muscle mass and strength
      during aging is the reduction in the number of functioning motor units (MU). It
      has been shown that lifelong physically active older rats have greater numbers of
      MU compared with age-matched sedentary controls, suggesting that chronic exercise
      may preserve MU function with advancing age. This has not previously been
      examined in humans. PURPOSE: Thus, the purpose of this study was to estimate the
      number of functioning MU in the tibialis anterior of masters runners
      (approximately 65 yr) and to compare the values with recreationally active young
      (approximately 25 yr) and healthy age-matched controls (approximately 65 yr).
      METHODS: Decomposition-enhanced spike-triggered averaging was used to collect
      surface and intramuscular EMG signals during dorsiflexion at 25% of maximum
      voluntary isometric contraction. RESULTS: The estimated number of MU did not
      differ between masters runners and young, but MU number estimates were lower in
      the old (91 +/- 22 MU) compared with the masters runners (140 +/- 53 MU) and
      young (150 +/- 43 MU). CONCLUSION: These results demonstrate that lifelong high
      intensity physical activity could potentially mitigate the loss of MU associated
      with aging well into the seventh decade of life.

PMID- 20142772
TI  - Ad libitum fluid replacement in military personnel during a 4-h route march.
AB  - INTRODUCTION: Opportunities to determine optimal rates of fluid ingestion could
      reduce the mass soldiers might need to carry on military missions. PURPOSE: The
      first objective was to evaluate the effects of an ad libitum fluid replacement
      strategy on total body water (TBW), core temperature, serum sodium concentrations
      [Na+], and plasma osmolality (POsm). The second objective was to determine if an
      ad libitum water intake was sufficient to maintain these variables during
      exercise. A third objective was to determine if changes in body mass are an
      accurate measure of changes in TBW. METHODS: A field study was conducted with 15
      soldiers performing a 16.4-km route march. The average age of 15 subjects was 27
      yr (SD = 4.6 yr). RESULTS: Their mean hourly ad libitum fluid intake was 383 mL
      (SD = 150 mL). Predicted sweat rate was 626 +/-122 mL.h-1. Despite an average
      body mass loss of 1.0 kg (SD = 0.50 kg) TBW, POsm and serum [Na+] did not change
      significantly during exercise. There was a significant (P < 0.05) linear
      relationship with a negative slope between postexercise serum [Na+] and changes
      in both body mass and percentage of TBW. Postexercise POsm and serum [Na+] were
      significantly related (P < 0.05). Higher postexercise percentage of TBW was
      associated with lower postexercise POsm and serum [Na+] levels. There was no
      relation between percent body mass loss and postexercise core temperature (38.1
      degrees C +/- 0.6 degrees C). CONCLUSIONS: A mean ad libitum water intake of 383
      mL.h-1, replacing approximately 61% of body mass losses during 4 h of exercise,
      maintained TBW, core temperature, POsm, and serum [Na+] despite a 1.4% body mass
      loss. A reduction in body mass of 1.4% (1.0 kg) was not associated with a
      reduction in TBW.

PMID- 20142773
TI  - Serum sodium concentration changes are related to fluid balance and sweat sodium
      loss.
AB  - PURPOSE: This study determined if changes in serum sodium concentration are
      related to fluid balance as well as sweat sodium losses in triathletes competing
      in the Hawaii Ironman triathlon. METHODS: Endurance trained athletes (N = 46, age
      = 24-67 yr) were studied during 30 min of stationary cycling at 70%-75% of HRmax
      in a warm outdoor laboratory (26.4 degrees C +/- 1.7 degrees C wet bulb globe
      temperature [WBGT], 28.3 degrees C +/- 1.2 degrees C dry bulb [DB]) 3-7 d before
      race day. Sweat sodium concentration was measured from absorbent patches on the
      forearm and scapula, and sweating rate was derived from changes in body mass.
      Before and after the race, serum sodium concentration, body mass, and nutritional
      intake during the race were also measured (N = 46). Sweating and race day
      comparisons and changes in serum sodium concentration were analyzed via Student's
      t-test, correlation, and multiple regression. RESULTS: In men, the change in
      serum sodium concentration during the race was correlated with relative sweating
      rate (mL.kg.h; r = -0.49, P = 0.012), rate of sweat sodium loss (mEq.kg.h; r = 
      0.44, P = 0.023), and body mass change (kg; r = -0.54, P = 0.005). Together, the
      rate of sweat sodium loss and body mass change accounted for 46% of the change in
      serum sodium concentration in men (R = 0.46). In women, body mass change alone
      was significantly correlated with the change in serum sodium concentration (r =
      0.31). The rate of sodium intake (mEq.kg.h) was related to the rate of sweat
      sodium loss in women (mEq.kg.h; r = 0.64, P = 0.035) but not in men (r = 0.27, P
      = 0.486). CONCLUSION: Changes in serum sodium concentration during an
      ultraendurance triathlon are significantly related to interactions of fluid
      balance, sweat sodium loss, and sodium ingestion.

PMID- 20142774
TI  - Fatigue-induced reductions of torque and shortening velocity are muscle
      dependent.
AB  - INTRODUCTION: In addition to torque (force) loss during dynamic fatiguing
      contractions, an important aspect of fatigue is the reduction in shortening
      velocity. Relatively few reports have studied changes in shortening velocity in
      response to fatigue, and inconsistencies in the results might depend on the
      muscle tested. To better understand fatigue-related changes in shortening
      velocity in different muscles, we compared the fatigue response of two muscles in
      humans with different physiological properties using the same criterion for task
      failure. METHODS: During separate sessions for the triceps brachii and soleus, 10
      young males performed repetitive shortening contractions with a moderate load
      (50% of maximum voluntary isometric contraction (MVC) torque) until they achieved
      a 50% reduction in loaded shortening velocity at task failure. RESULTS: In the
      unfatigued condition, these muscles expressed different physiological features
      with similar power output but approximately 1.5 times slower shortening velocity,
      approximately 1.4 times slower normalized evoked 50-Hz maximum rate of
      relaxation, and approximately 47% lower postactivation potentiation in the soleus
      compared with the triceps brachii. During the fatiguing task, significantly less
      total work was performed in the soleus ( approximately 1986 J) compared with the
      triceps brachii ( approximately 3940 J), suggesting greater endurance in the
      triceps brachii. Despite similar relative reductions in shortening velocity in
      both muscles at task failure, the soleus had a smaller reduction in MVC torque
      than the triceps brachii at task failure. Furthermore, in both muscles, there was
      a greater reduction at task failure and a faster restoration of shortening
      velocity compared with MVC torque. CONCLUSION: Our findings suggest that fatigue
      related mechanisms that reduce torque are not the same as those that reduce
      shortening velocity.

PMID- 20142775
TI  - Scapular rotation to attain the peak shoulder external rotation in tennis serve.
AB  - PURPOSE: The purposes of this study were (a) to describe the detailed movements
      of the shoulder complex during the cocking phase in tennis serve and (b) to
      determine the contribution of the scapular rotation to the peak shoulder external
      rotation attained at the end of the cocking phase. METHOD: Twenty tennis players
      performed flat tennis serves with the maximum effort, and three-dimensional
      kinematic data of the thorax, scapula, and humerus of the dominant side were
      recorded by an electromagnetic tracking device (Liberty; Polhemus) at 240 Hz. The
      humeral rotation with respect to the thorax (named as the resultant shoulder
      rotation) was decomposed into the scapular rotation with respect to the thorax
      and the humeral rotation with respect to the scapula (named as the glenohumeral
      rotation). The scapular rotation that contributed to attain the peak resultant
      shoulder external rotation was quantitatively determined, and the ratio of the
      glenohumeral external rotation to the scapular rotation that contributed to
      attain the peak resultant shoulder external rotation was computed to represent
      the scapulohumeral rhythm for shoulder external rotation. RESULTS: Of the three
      components of scapular rotations, the scapular posterior tilt was the primary
      component that contributed to the attainment of the peak resultant shoulder
      external rotation. The scapulohumeral rhythm for shoulder external rotation
      (scapular posterior tilt-glenohumeral external rotation) exhibited during the
      backswing phase was 1:2.3. CONCLUSIONS: The peak resultant shoulder external
      rotation was generated by a synchronized combination of the scapular posterior
      tilt and glenohumeral external rotation. A consistent pattern of three phases of
      the scapular posterior tilt and the glenohumeral external rotation that could be
      accurately modeled by three linear regressions was observed in preparation for
      the peak shoulder external rotation in tennis serve.

PMID- 20142776
TI  - Defining intensity domains from the end power of a 3-min all-out cycling test.
AB  - PURPOSE: The purpose of this study was to develop a modified version of a 3-min
      all-out cycling test (3MT) using equipment readily available to cyclists and to
      identify exercise intensity domains using the average power output over the last
      30 s of the 3MT (end-test power (EP)). METHODS: Sixteen competitive cyclists
      (V(O2peak) = 60.3 +/- 8.3 mL.kg.min) completed three laboratory visits using
      their own bicycles and a power-measuring rear wheel. In visit 1, subjects
      performed an incremental load test to volitional termination on an electronically
      braked trainer (100 + 25 W every 4 min). Power output at lactate threshold was
      determined by absolute 4 mmol.L (OBLA-PO) and 1 mmol.L over exercise baseline (LT
      PO). Power output at ventilatory threshold (VT-PO) was computed on the basis of
      the V-slope method. Power output at V(O2peak) (V(O2peak)-PO) was the mean power
      observed during the stage at which peak O2 consumption was recorded. In visits 2
      and 3, subjects performed the 3MT using a progressive resistance trainer with
      Visit 2 as a familiarization trial. During Visit 3, EP was recorded. RESULTS: EP
      (273 +/- 52 W) was significantly greater than VT-PO, OBLA-PO, and LT-PO (232 +/-
      64, 235 +/- 54, and 208 +/- 45 W, respectively) but significantly less than
      V(O2peak)-PO (288 +/- 56 W). EP was correlated with V(O2peak)-PO (r = 0.97), VT
      PO (r = 0.87), OBLA-PO (r = 0.85), and LT-PO (r = 0.79) with regression estimates
      through the origin made using 105%, 86%, 86%, and 76% of EP, respectively.
      Demarcations for moderate- to heavy-intensity (LT-PO at 76% EP) and heavy- to
      severe-intensity (100% EP) domains may be estimated. CONCLUSION: The 3MT can be
      used to define exercise intensity in competitive cyclists using readily available
      equipment.

PMID- 20142777
TI  - Joint-specific power loss after eccentric exercise.
AB  - Previous investigators have reported changes in maximal power after eccentric
      exercise. The influence of eccentric joint-specific power absorption on
      subsequent concentric joint-specific power production during multijoint actions
      has not been reported. PURPOSE: Our purposes were to determine the extent to
      which ankle, knee, and hip joint actions absorbed power during eccentric cycling
      (ECCcyc) and to evaluate changes in power produced by those joint actions during
      subsequent maximal concentric cycling (CONcyc). We hypothesized that joint
      actions that absorbed the most power during ECCcyc would exhibit the greatest
      reductions in power during subsequent maximal CONcyc. METHODS: Nineteen cyclists
      performed baseline trials of maximal single-leg CONcyc immediately before and 24
      h after acute single-leg ECCcyc (5 min, 40% maximum single-leg CONcyc power).
      Pedal forces and limb kinematics were determined with a force-sensing pedal and
      instrumented spatial linkage system, respectively. Joint-specific powers were
      calculated using inverse dynamics and averaged over complete crank revolutions
      and over extension and flexion phases. RESULTS: The largest power-absorbing
      actions during ECCcyc were eccentric knee extensor activity (-185 +/- 12 W)
      followed by eccentric hip extensor activity (-92 +/- 12 W). Power absorbed
      through ankle joint actions was small (-10 +/- 2 W). At 24 h, pedal power
      produced during maximal CONcyc was reduced by 11% +/- 3% relative to baseline.
      Compared with baseline, knee extension power was reduced by 19% +/- 0 7%, whereas
      hip extension power did not differ. CONCLUSIONS: Power absorbed through eccentric
      knee extension actions significantly reduced knee extension power produced during
      subsequent maximal CONcyc. Even with reduced knee extensor function, participants
      were able to deliver 89% of their baseline power to the environment. These
      results have implications for individuals who must continue to perform multijoint
      activities after eccentric exercise.

PMID- 20142778
TI  - Validation of the ActiGraph two-regression model for predicting energy
      expenditure.
AB  - PURPOSE: The purpose of this study was to validate a two-regression model for
      predicting energy expenditure (EE) from ActiGraph GT1M accelerometer-generated
      activity counts using a whole-room indirect calorimeter and the doubly labeled
      water (DLW) technique. We also investigated if a low-pass filter (LPF) approach
      would improve the model's accuracy in the minute-to-minute EE prediction.
      METHODS: Thirty-four healthy volunteers (age = 20-67 yr, body mass index = 19.3
      52.1 kg.m) spent approximately 24 h in a room calorimeter while wearing a GT1M
      monitor and performed structured and self-selected activities followed by
      overnight sleep. The EE predicted by the models and expressed in metabolic
      equivalents (MET-minutes) during waking times was compared with the room
      calorimeter-measured EE. A subset of volunteers (n = 22) completed a 14-d DLW
      protocol in free living while wearing an ActiGraph. The average daily EE
      predicted by the models (MET-minutes) was compared with the DLW. RESULTS:
      Compared with the room calorimeter, the two-regression model overpredicted EE by
      10.2% +/- 11.4% (1282 +/- 125 and 1174 +/- 152 MET.min, P < 0.001) and time spent
      in moderate physical activity (PA) by 36.9 +/- 46.0 min while underestimating the
      time spent in light PA by -48.3 +/- 55.0 min (P < 0.05). The LPF reduced the
      squared and mean absolute error in the EE prediction (P < 0.05) but not the
      prediction error in time spent in moderate or light PA (both P > 0.05). The EE
      measured by DLW (2108 +/- 358 MET.min.d) and predicted by both filtered and
      unfiltered models (2104 +/- 218 and 2192 +/- 228 MET.min.d, respectively) were
      similar (P > 0.05). CONCLUSIONS: The two-regression model with LPF showed good
      agreement with total EE measured using room calorimeter and DLW. However, the
      individual variability in assessing time spent in sedentary, low, and moderate PA
      intensities and related EE remains significant.

PMID- 20142779
TI  - Harmful effect of land-based endurance exercise in rats with diabetic nerve.
AB  - PURPOSE: Repetitive limb movements made during aerobic exercises, such as walking
      and jogging that are frequently prescribed for diabetes control, can induce nerve
      strain, which has been reported to induce nerve ischemia. Nerves in a diabetic
      background are more vulnerable to ischemia. We investigated the effects of
      repetitive treadmill and swimming exercises on nerves in diabetic rats. METHODS:
      Rats with diabetic neuropathy were randomly allocated to one of three groups,
      namely, control (n = 7), treadmill (n = 8), and swimming (n = 8) groups. After 12
      wk of exercise, sural and sciatic nerves were harvested and analyzed by Terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Western blotting.
      RESULTS: In sural nerves, percentages of TUNEL-positive cells and BAX/GAPDH level
      were higher in the treadmill than that in the swimming group. In sciatic nerves,
      there was no significant difference among three groups. CONCLUSIONS: : Endurance
      exercises increase Schwann cell apoptosis in distal peripheral nerves. Greater
      loadings during exercise were found to increase Schwann cell apoptosis. Land
      based endurance exercises may have a harmful effect on peripheral nerves in
      certain individuals with diabetes.

PMID- 20142780
TI  - Descriptive epidemiology of youth pedometer-determined physical activity:
      CANPLAY.
AB  - PURPOSE: Objective measurement with body worn instrumentation is a preferred and
      increasingly common way to gather information about young people's physical
      activity. Measured samples have been typically small and recruited through
      schools. The purpose of this article was to present the descriptive epidemiology
      of children and youth pedometer-determined physical activity on the basis of a
      large national sample. METHODS: Children and youth (19,789) were recruited
      through random digit dialing. Participants were asked to wear the pedometer for
      seven consecutive days and to log daily steps. Of the 58% of participants who
      returned pedometer data, 95% wore the pedometer for at least 5 d. Daily step
      counts below 1000 or above 30,000 steps were truncated accordingly, and all
      values were included in the descriptive analysis. RESULTS: Boys and girls aged 5
      19 yr took 12,259 and 10,906 steps per day, respectively. Daily steps were higher
      among boys than girls and declined by age group in a pattern consistent with that
      predicted by other smaller samples internationally. Weekday steps per day were
      generally higher than weekend day steps per day and varied by season.
      CONCLUSIONS: This study demonstrates the viability of using relatively
      inexpensive pedometers and methods for the surveillance of young people's
      physical activity. The resulting descriptive data provide key information
      regarding the population distribution of pedometer-determined physical activity
      that may be useful for identifying target groups for population strategies and
      other interventions.

PMID- 20142782
TI  - Effect of positive health factors and all-cause mortality in men.
AB  - PURPOSE: Although several health-related factors are independently associated
      with diverse health outcomes, their combined affect on mortality has not been
      fully described. METHODS: We examined the combined effect of several positive
      health factors, including having normal weight (body mass index = 18.5-24.9
      kg.m), not smoking (not current smoker), consuming a moderate alcohol intake (1
      14 drinks per week), being physically active (moderate to high level), and having
      a higher cardiorespiratory fitness (top two-thirds), on all-cause mortality in
      38,110 men aged 20-84 yr from the Aerobics Center Longitudinal Study. RESULTS:
      There were 2642 deaths during an average of 16 yr of follow-up. Compared with men
      with zero positive health factors, the multivariable-adjusted hazard ratios (HR)
      of all-cause mortality with one, two, three, four, and five positive health
      factors were 0.78 (95% confidence interval (CI) = 0.64-0.95), 0.61 (95% CI = 0.50
      0.73), 0.54 (95% CI = 0.44-0.65), 0.43 (95% CI = 0.35-0.52), and 0.39 (95% CI =
      0.31-0.48), respectively (P for trend <0.001). The combination of five positive
      health factors accounted for 29% (95% CI = 14%-40%) of population-attributable
      risk for all-cause mortality. CONCLUSIONS: Our findings suggest that targeting
      more of these modifiable health factors may provide substantial health benefits
      in middle-aged men.

PMID- 20142781
TI  - Accelerometer output and MET values of common physical activities.
AB  - PURPOSE: This article 1) provides the calibration procedures and methods for
      metabolic and activity monitor data collection, 2) compares measured MET values
      to the MET values from the compendium of physical activities, and 3) examines the
      relationship between accelerometer output and METs for a range of physical
      activities. METHODS: Participants (N = 277) completed 11 activities for 7 min
      each from a menu of 23 physical activities. Oxygen consumption (V O2) was
      measured using a portable metabolic system, and an accelerometer was worn. MET
      values were defined as measured METs (V O2/measured resting metabolic rate) and
      standard METs (V O2/3.5 mL.kg.min). For the total sample and by subgroup (age
      [young < 40 yr], sex, and body mass index [normal weight < 25 kg.m]), measured
      METs and standard METs were compared with the compendium, using 95% confidence
      intervals to determine statistical significance (alpha = 0.05). Average counts
      per minute for each activity and the linear association between counts per minute
      and METs are presented. RESULTS: Compendium METs were different than measured
      METs for 17/21 activities (81%). The number of activities different than the
      compendium was similar between subgroups or when standard METs were used. The
      average counts for the activities ranged from 11 counts per minute (dishes) to
      7490 counts per minute (treadmill: 2.23 m.s, 3%). The r between counts and METs
      was 0.65. CONCLUSIONS: This study provides valuable information about data
      collection, metabolic responses, and accelerometer output for common physical
      activities in a diverse participant sample. The compendium should be updated with
      additional empirical data, and linear regression models are inappropriate for
      accurately predicting METs from accelerometer output.

PMID- 20142783
TI  - Acute cardiorespiratory responses to inspiratory pressure threshold loading.
AB  - PURPOSE: We tested the acute responses to differing pressure threshold
      inspiratory loading intensities in well-trained rowers. The purpose of this study
      was to evaluate 1) how the magnitude of inspiratory pressure threshold loading
      influences repetition maximum (RM), tidal volume (VT), and external work
      undertaken by the inspiratory muscle; and 2) whether the inspiratory muscle
      metaboreflex is activated during acute inspiratory pressure threshold loading.
      METHODS: Eight males participated in seven trials. Baseline measurements of
      maximal inspiratory pressure (PImax), resting tidal volume (VT), and forced vital
      capacity (FVC) were made. During the remaining sessions, participants undertook a
      series of resistive inspiratory breathing tasks at loads corresponding to 50%,
      60%, 70%, 80%, and 90% of PImax using a pressure threshold inspiratory muscle
      trainer. The number of repetitions completed at each load, VT, heart rate (fc),
      and measures of arterial blood pressure was assessed continuously during each
      trial. RESULTS: A standardized cutoff of 10% FVC was used to define the RM, which
      decreased as loading intensity increased (P < 0.05). This response was nonlinear,
      with an abrupt decrease in RM occurring at loads > or =70% of PImax. The most
      commonly used inspiratory muscle training regimen of 30RM corresponded to 62.5%
      +/- 4.6% of PImax and also resulted in the highest external work output. Tidal
      volume (VT) decreased significantly over time at 60%, 70%, and 80% of PImax (P <
      0.05), as did the amount of external work completed (P<0.05). CONCLUSIONS:
      Although all loads elicited a sustained increase in fc, only the 60% load
      elicited a sustained rise in mean arterial blood pressure (P = 0.016), diastolic
      blood pressure (P = 0.015), and systolic blood pressure (P = 0.002), providing
      evidence for a metaboreflex response at this load.

PMID- 20142784
TI  - Changes in the eccentric phase contribute to improved stretch-shorten cycle
      performance after training.
AB  - PURPOSE: To determine whether ballistic power training and strength training
      result in specific changes in stretch-shorten cycle (SSC) function during the
      eccentric (ECC) phase and, if so, whether these changes are influenced by the
      individual's strength level. METHODS: Thirty-two male subjects were divided into
      four groups: stronger power training group (SP, n = 8, squat one-repetition
      maximum-to-body mass ratio (1RM/BM) = 1.97 +/- 0.08), weaker power training group
      (WP, n = 8, 1RM/BM = 1.32 +/- 0.14), weaker strength training group (WS, n = 8,
      1RM/BM = 1.28 +/- 0.17), or control group (C, n = 8, 1RM/BM = 1.37 +/- 0.13).
      Training involved three sessions per week for 10 wk. The SP and WP groups
      performed maximal-effort jump squats with 0%-30% 1RM, and the WS group performed
      back squats at 75%-90% 1RM. Maximal strength, jump performance, musculotendinous
      stiffness, and neural activation were assessed before training and after 5 and 10
      wk of training. RESULTS: Both power and strength training elicited significant
      changes in a multitude of ECC variables that were significantly associated with
      improvements in concentric (CON) performance. Enhancements in CON performance
      were theorized to be driven by the development of a strategy to better use the
      ECC phase during jumping (i.e., greater unloading allowed for increased negative
      acceleration and thus velocity during the countermovement and improved
      musculotendinous stiffness resulted in an enhanced ability to translate the
      momentum developed during the ECC phase into force). Although a significant
      improvement in maximal strength resulted in changes to SSC function during the
      ECC phase, the initial strength level did not significantly affect the ECC
      variables before training or the magnitude of adaptations in individuals exposed
      to ballistic power training. CONCLUSIONS: Training-induced alterations in SSC
      function during the ECC phase contributes to improvements in jump performance
      after both ballistic power training and heavy strength training.

PMID- 20142785
TI  - Long-term outcomes of vasomotor symptom treatments: what happens after we pull
      the plug--or the needles.

PMID- 20142786
TI  - Another multibotanical for vasomotor symptoms: some lessons learned.

PMID- 20142787
TI  - The role of acupuncture in treating menopausal hot flashes.

PMID- 20142788
TI  - Are hot flashes linked to cardiovascular risk? It is too early to tell.

PMID- 20142789
TI  - Red clover extract: a source for substances that activate peroxisome proliferator
      activated receptor alpha and ameliorate the cytokine secretion profile of
      lipopolysaccharide-stimulated macrophages.
AB  - OBJECTIVE: Inflammation and hyperlipidemia or dyslipidemia contribute to an
      increased risk of atherosclerosis and cardiovascular disease. Cardiovascular
      disease represents one of the major causes of premature death worldwide. The
      activation of peroxisome proliferator-activated receptor (PPAR) alpha, a drug
      target for hyperlipidemia and dyslipidemia, leads to an improved blood lipid
      profile. In this study, we determined the putative anti-inflammatory and
      PPARalpha stimulatory activities of red clover, an alternative to the classic
      hormone therapy used currently to treat menopausal symptoms. METHODS:
      Lipopolysaccharide-induced macrophages were used as a model for anti-inflammatory
      activity, and a chimeric GAL4-PPARalpha system was used as a model for putative
      hypolipidemic activity. RESULTS: Red clover extract and the isoflavones genistein
      and biochanin A were moderate PPARalpha activators. Daidzein only slightly
      activated PPARalpha, but its metabolite 6-hydroxydaidzein exerted a much higher
      PPARalpha activity. Similarly, the metabolite 3'-hydroxygenistein achieved higher
      activation efficiency than its precursor, genistein, did. In lipopolysaccharide
      stimulated macrophages, red clover extract and its compounds reduced the
      secretion of proinflammatory cytokines, interleukin-6 and tumor necrosis factor
      alpha, increased the secretion of the anti-inflammatory interleukin-10, and/or
      reduced the expression of nuclear factor-kappaB, inducible nitric oxide synthase,
      and/or cyclooxygenase 2. Tumor necrosis factor alpha production was most
      efficiently reduced by biochanin A and genistein. Interleukin-6 levels were most
      efficiently reduced by genistein and equol. CONCLUSIONS: Owing to its PPARalpha
      activation and modulation of the secreted cytokine profile, red clover extract is
      a putative candidate for preventing atherosclerosis and, thus, cardiovascular
      disease.

PMID- 20142790
TI  - Appetitive hormones, but not isoflavone tablets, influence overall and central
      adiposity in healthy postmenopausal women.
AB  - OBJECTIVE: One of the multiple health benefits of soy protein or its isoflavones
      may be their purported favorable effect on body composition. We examined the
      effect of isoflavones extracted from soy protein on overall and regional body
      composition, taking into account appetitive hormones as potential mediators, as
      well as the direct effect on appetitive hormones. METHODS: This randomized,
      double-blind, placebo-controlled multicenter trial included 229 healthy
      postmenopausal women (age, 45.8-65 y; body mass index, 24.9 +/- 3.0 kg/m) who
      consumed placebo or soy isoflavone (80 or 120 mg/d) tablets for 12 months. We
      used intent-to-treat analysis to examine changes in body composition (whole-body
      lean mass, whole-body fat mass, androidal fat mass, and androidal-to-gynoidal fat
      mass ratio) and appetitive hormones (insulin, leptin, ghrelin, and adiponectin)
      in response to treatment. RESULTS: Repeated-measures analysis of variance
      indicated that soy isoflavone treatment did not exert a significant effect on
      body composition measures (P value from 0.36 to 0.79) or appetitive hormone
      concentrations; the inclusion of covariates in statistical models did not alter
      these results. Independently of treatment, leptin and ghrelin related inversely
      to each body composition measure (P values from 0.044 to < or = 0.0001).
      Adiponectin related inversely to all fat measures (P values from 0.0004 to
      <0.0001). Time since last menstrual period related directly to all fat measures
      (P values from 0.06 to 0.0055). Dietary fat contributed to whole-body (P = 0.028)
      and androidal (P = 0.017) fat mass. CONCLUSIONS: Our findings do not support a
      favorable effect of soy isoflavone tablets on body composition in healthy
      postmenopausal women.

PMID- 20142791
TI  - Ovariectomy in aged versus young rats augments matrix metalloproteinase-mediated
      vasoconstriction in mesenteric arteries.
AB  - OBJECTIVE: Ovarian deficiency is known to undermine vasoprotective mechanisms and
      accelerate cardiovascular disease in postmenopausal women. In a rat model of
      menopause (aged ovariectomized [Ovx] rats), we recently revealed a
      vasoconstrictor pathway mediated by matrix metalloproteinases (MMPs) via cleavage
      of big endothelin-1 (ET-1). However, the specific impact of aging and/or Ovx on
      this pathway remains unknown. We hypothesized that aging exacerbates MMP-mediated
      vasoconstriction in an ovary-deficient state. METHODS: Young and aged female
      Sprague-Dawley rats, either intact or Ovx, were assessed for MMP-dependent
      vasoreactivity. Dose responses to big ET-1 in the absence or presence of an MMP
      inhibitor (GM6001) were tested on small mesenteric arteries using a pressure
      myograph system. MMP levels in the vascular tissue were measured by gelatin
      zymography. RESULTS: Both young Ovx and aged Ovx animals demonstrated a similar
      increase in the vasoconstriction to big ET-1 compared with the age-matched intact
      groups. MMP inhibition attenuated big ET-1 response in both Ovx groups and aged
      controls, but this effect was more pronounced in aged Ovx arteries (area under
      the curve reduction, 3.8 +/- 0.6 units in aged Ovx rats vs 1.5 +/- 0.5 units in
      young Ovx rats or 1.8 +/- 0.6 units in aged intact rats; P < 0.05). MMP-2
      activity in the vascular tissue increased with age and was further augmented by
      Ovx. CONCLUSIONS: Regardless of age, ovarian loss increases vascular reactivity
      to big ET-1, which is mediated, in part, by MMP. Superimposed with advancing age,
      ovarian deficiency further increases the proconstrictor role of MMP, which
      corresponds with higher MMP-2 levels in the aging vessel wall. MMP-mediated
      vasoconstriction may be a mechanism contributing to vascular dysfunction in
      postmenopausal women.

PMID- 20142792
TI  - Item banking: a generational change in patient-reported outcome measurement.
AB  - PURPOSE: Patient-reported outcomes are traditionally measured with questionnaires
      and many have been developed to measure Vision-Related Activity Limitation (VRAL;
      visual disability or visual functioning), Symptoms, and Quality Of Life (QOL).
      These vary in quality and can be classified as First or Second Generation
      instruments. First generation instruments are characterized by simple summary
      scoring of ordinal responses, which precludes interval measurement. This problem
      is solved in second generation instruments where Rasch analysis is used to
      optimize psychometric properties. However, second generation instruments retain
      limitations; difficulties in comparing scores across instruments, limited
      applicability to populations and inability to adapt to change. A third generation
      approach to patient-reported outcomes measurement, item banking, can solve these
      problems. The aim of this project was to use Rasch analysis to calibrate all
      items from all instruments to form VRAL, Symptoms, and QOL Item Banks. METHODS:
      Six hundred twenty-four people on the waiting list for cataract surgery were
      recruited. Each participant completed, by self-administration, a number of the 19
      instruments. A total of 353 items were calibrated using Rasch analysis (Winsteps
      v3.67). The psychometric properties of each item bank were optimized; items
      fitting the Rasch model were retained (Infit and Outfit range, 0.50 to 1.50).
      RESULTS: Items were sorted into the three traits; 226 tapped VRAL, 22 symptoms,
      and 60 QOL. Satisfactory measurement of each latent trait occurred with person
      separation of 8.11 for VRAL, 2.33 for Symptoms, and 3.20 for QOL. Rasch estimates
      of item difficulty were highly stable with an average standard error of 0.11
      logits. CONCLUSIONS: Item banks for the measurement of the latent traits of VRAL,
      symptoms, and QOL have been formed. New items can be added to enable evolution of
      measurement. Item banking facilitates accurate and precise measurement through
      computer adaptive testing. This approach provides common measurement scales,
      facilitating worldwide comparison of results.

PMID- 20142794
TI  - Gadolinium uptake in the rat inner ear perilymph evaluated with 4.7 T MRI: a
      comparison between transtympanic injection and gelatin sponge-based diffusion
      through the round window membrane.
AB  - OBJECTIVE: To investigate the inner ear uptake of the contrast agent gadolinium
      administered intratympanically through transtympanic injection or using a gelatin
      sponge placed on the round window. MATERIALS AND METHODS: The T1 contrast agent
      Gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) was administrated
      to the middle ear cavities of 12 male Wistar rats by a transtympanic injection
      technique (TTI group; 40 microl), gelatin sponge diffusion (GelD40 group; 40
      microl), or gelatin sponge diffusion (GelD8 group; 8 microl). Magnetic resonance
      imaging was performed with a 4.7-T scanner using a T1-weighted 2-dimensional
      rapid acquisition with relaxation enhancement sequence and a high-resolution T1
      weighted 3-dimensional rapid acquisition with relaxation enhancement sequence.
      RESULTS: The uptake of Gd-DOTA into the perilymph was more pronounced at 3 than
      at 1 hour after intratympanic administration for all methods studied.
      Transtympanic injection and GelD40 induced similar uptake of Gd-DOTA in the lower
      turns of the rat cochlea. Transtympanic injection induced less efficient Gd-DOTA
      uptake in the apex than GelD40. GelD8 was less efficient at Gd-DOTA uptake than
      either TTI or GelD40. CONCLUSION: Both TTI and GelD40 are able to efficiently
      deliver substances to inner ear destinations. Considering its simplicity, TTI is
      more practical for use in the clinic for the administration of substances to the
      inner ear, although it provided less efficient uptake in the apex than GelD40.

PMID- 20142795
TI  - Rheumatoid arthritis involved in the ear drum.

PMID- 20142793
TI  - Dynamic regulation of barrier integrity of the corneal endothelium.
AB  - The corneal endothelium maintains stromal deturgescence, which is a prerequisite
      for corneal transparency. The principal challenge to stromal deturgescence is the
      swelling pressure associated with the hydrophilic glycosaminoglycans in the
      stroma. This negative pressure induces fluid leak into the stroma from the
      anterior chamber, but the rate of leak is restrained by the tight junctions of
      the endothelium. This role of the endothelium represents its barrier function. In
      healthy cornea, the fluid leak is counterbalanced by an active fluid pump
      mechanism associated with the endothelium itself. Although this pump-leak
      hypothesis was postulated several decades ago, the mechanisms underlying
      regulation of the balance between the pump and leak functions remain largely
      unknown. In the last couple of decades, the ion transport systems that support
      the fluid pump activity have been discovered. In contrast, despite significant
      evidence for corneal edema secondary to endothelial barrier dysfunction, the
      molecular aspects underlying its regulation are relatively unknown. Recent
      findings in our laboratory, however, indicate that barrier integrity (i.e.,
      structural and functional integrity of the tight junctions) of the endothelium is
      sensitive to remodeling of its peri-junctional actomyosin ring, which is located
      at the apical junctional complex. This review provides a focused perspective on
      dynamic regulation of the barrier integrity of endothelium vis-a-vis plasticity
      of the peri-junctional actomyosin ring and its association with cell signaling
      downstream of small GTPases of the Rho family. Based on findings to date, it
      appears that development of specific pharmacological strategies to treat corneal
      edema in response to inflammatory stress would be possible in the near future.

PMID- 20142796
TI  - Prevalence and timing of individual cochlear implant electrode failures.
AB  - OBJECTIVE: To identify the prevalence of individual electrode failures as a
      result of open and short circuits in the Nucleus N24 and Freedom series and the
      Advanced Bionics CII and HR90k (Helix and 1J) devices. STUDY DESIGN:
      Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Age at
      implantation, date of surgery, device type, and other relevant demographic data
      in addition to telemetry and impedance data were collected on 636 implants.
      INTERVENTION(S): Individual electrode circuit failures were identified using
      impedance testing performed intraoperatively and during subsequent programming
      sessions. MAIN OUTCOME MEASURE(S): Individual electrode failures were categorized
      as either "short" or "open" circuits as determined by manufacturer software
      algorithms. RESULTS: Combining all devices, the risk of 1 or more failures as
      determined by impedance telemetry is 9.0%. Three or more individual electrode
      circuit failures within an array may indicate impending deterioration of device
      performance and future need of reimplantation. CONCLUSION: Open and short
      circuits are routinely encountered. They can be managed by deactivating the
      affected electrode(s), and conventional wisdom states that this has little impact
      on performance. However, it is true that multiple failures are often associated
      with decreased performance and often lead to revision surgery. Certainly, every
      patient would prefer to have a fully functional device. Continued reporting of
      individual electrode circuit failures is critical to product development and
      improving overall device reliability.

PMID- 20142797
TI  - Torque measurements of the ossicular chain: implication on the MRI safety of the
      hearing implant Vibrant Soundbridge.
AB  - HYPOTHESIS: Is the human ossicular chain stabile enough to withstand the torque
      of a Vibrant Soundbridge middle ear hearing implant in the magnetic field of a
      1.5 T magnetic resonance imaging (MRI) system? BACKGROUND: The Vibrant
      Soundbridge is a semi-implantable hearing device in which a tiny
      electromechanical transducer, called floating mass transducer (FMT), is clipped
      to the ossicular chain within the middle ear. The FMT contains a permanent
      magnet, which can generate a torque when exposed to a static magnetic field of
      MRI systems. Since the transducer is routinely attached to the long process of
      the incus, this torque could affect or even disrupt the ossicular chain. This
      study investigates the likelihood of a middle ear injury by an FMT in an MRI
      system. METHODS: Torque measurements were performed on 10 unpreserved human
      temporal bones. A brass fork was attached to the long process of the incus via a
      posterior tympanotomy, and a defined torque was applied by a calibrated torque
      meter. The torque was increased stepwise until an injury of the middle ear was
      observed. RESULTS: The mean torque at which the middle ear was injured was 4.3
      mN.m +/- 1.7 mN.m. The lowest value measured was 1.5 mN.m, and the highest was
      6.5 mN.m. CONCLUSION: Even the lowest torque measured is more than 1.5 times
      higher than the "worst-case" torque affecting the FMT during a 1.5 T MRI
      examination. The torque on an FMT crimped to the long process of the incus should
      therefore not harm the human middle ear.

PMID- 20142798
TI  - The internal dimensions of the cochlear scalae with special reference to cochlear
      electrode insertion trauma.
AB  - HYPOTHESIS: To investigate the intracochlear micromorphology with regard to
      frequent patterns of cochlear electrode insertion trauma. OBJECTIVE: Cochlear
      implantation is a widely accepted treatment for deafness and high-grade
      sensorineural hearing loss. Although the device and the implantation methods are
      continuously optimized, damage of intracochlear structures due to electrode
      insertion is a frequent finding in temporal bone studies. Reduction of
      insertional trauma is important for the preservation of residual hearing and on
      the background of increasing numbers of cochlear implant recipients. MATERIALS
      AND METHODS: This study was performed with histologic specimens from the
      "Wittmaack temporal bone collection" (Hamburg, Germany) to examine the diameters
      of intracochlear spaces and to correlate the micromorphology of cochlear ducts to
      frequent patterns of intracochlear insertion trauma. RESULTS: The diameter of the
      scala tympani decreases by approximately 300 microm during the ascending part of
      the basal turn. In this region, the intersegmental decrease exceeds the assumed
      linear diameter decrease significantly (p < or = 0.001). The regression of the
      cross-sectional diameter is accompanied by a shift of the spiral osseous lamina
      toward the scala tympani and by narrowing of the bony capsule of the cochlea.
      CONCLUSION: Various attempts have been made to evaluate the dimensions of the
      cochlea related to cochlear implantation. Little attention was paid to the
      distinct narrowing of the scala tympani in the region of the ascending part of
      the cochlear duct, although from the literature, it is known that electrode
      insertion trauma frequently occurs here. Individual variations of the cochlear
      micromorphology may additionally contribute to the failure of preformed electrode
      arrays, but the challenge of guiding the electrode array around the first bend of
      the cochlear turn, that is, the pars ascendens, is obviously impaired by the
      interindividually constant narrowing in this area. Therefore, this finding may
      have implications on the development of electrode designs and insertion methods.

PMID- 20142799
TI  - Imaging mismatch repair and cellular responses to DNA damage in Bacillus
      subtilis.
AB  - Both prokaryotes and eukaryotes respond to DNA damage through a complex set of
      physiological changes. Alterations in gene expression, the redistribution of
      existing proteins, and the assembly of new protein complexes can be stimulated by
      a variety of DNA lesions and mismatched DNA base pairs. Fluorescence microscopy
      has been used as a powerful experimental tool for visualizing and quantifying
      these and other responses to DNA lesions and to monitor DNA replication status
      within the complex subcellular architecture of a living cell. Translational
      fusions between fluorescent reporter proteins and components of the DNA
      replication and repair machinery have been used to determine the cues that target
      DNA repair proteins to their cognate lesions in vivo and to understand how these
      proteins are organized within bacterial cells. In addition, transcriptional and
      translational fusions linked to DNA damage inducible promoters have revealed
      which cells within a population have activated genotoxic stress responses. In
      this review, we provide a detailed protocol for using fluorescence microscopy to
      image the assembly of DNA repair and DNA replication complexes in single
      bacterial cells. In particular, this work focuses on imaging mismatch repair
      proteins, homologous recombination, DNA replication and an SOS-inducible protein
      in Bacillus subtilis. All of the procedures described here are easily amenable
      for imaging protein complexes in a variety of bacterial species.

PMID- 20142800
TI  - CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2,
      inhibit angiogenesis both in vitro and in vivo.
AB  - Integrins are essential in the complex multistep process of angiogenesis and are
      thus attractive targets for the development of antiangiogenic therapies.
      Integrins are antagonized by disintegrins and C-type lectin-like proteins, two
      protein families from snake venom. Here, we report that CC-PLA2-1 and CC-PLA2-2,
      two novel secreted phospholipases A(2) (PLA(2)) isolated from Cerastes cerastes
      venom, also showed anti-integrin activity. Indeed, both PLA(2)s efficiently
      inhibited human brain microvascular endothelial cell adhesion and migration to
      fibrinogen and fibronectin in a dose-dependent manner. Interestingly, we show
      that this anti-adhesive effect was mediated by alpha5beta1 and alphav-containing
      integrins. CC-PLA2s also impaired in vitro human brain microvascular endothelial
      cell tubulogenesis on Matrigel and showed antiangiogenic activity in vivo in
      chicken chorioallantoic membrane assay. The complete PLA(2) cDNAs were cloned
      from a venom gland cDNA library. Mature CC-PLA2-1 and CC-PLA2-2 contain 121 and
      120 amino acids, respectively, including 14 cysteines each and showed 83%
      identity. Tertiary model structures of CC-PLA2-1 and CC-PLA2-2 were generated by
      homology modeling. This is thus the first study describing an antiangiogenic
      effect for snake venom PLA(2)s and reporting first clues to their mechanism of
      action on endothelial cells.

PMID- 20142801
TI  - Absence of placental growth factor blocks dextran sodium sulfate-induced colonic
      mucosal angiogenesis, increases mucosal hypoxia and aggravates acute colonic
      injury.
AB  - Angiogenesis has recently been described as a component of inflammatory bowel
      disease. Placental growth factor (PlGF), a vascular endothelial growth factor
      (VEGF) homologue, establishes its angiogenic capacity under pathophysiological
      conditions. We investigated the function of PlGF in experimental models of acute
      colitis. Acute colonic damage was induced in PlGF knock-out ((-/-)) mice and PlGF
      wild-type ((+/+)) mice by dextran sodium sulfate (DSS) and
      trinitrobenzenesulfonic acid (TNBS). The concentrations of PlGF and VEGF were
      measured in distal colonic lysates using an enzyme-linked immunosorbent assay.
      Colonic injury was evaluated by assessing colon length, colonocyte apoptosis (by
      terminal dUTP nick-end labeling), colonic cytokine production and histological
      score. Infiltration of polymorphonuclear cells was determined by assaying
      myeloperoxidase (MPO) activity. In a separate experiment, recombinant PlGF was
      administered to PlGF(-/-) mice by adenoviral transfer before DSS administration.
      Mucosal vascularization was quantified by computerized morphometric analysis of
      CD31-stained distal colonic sections. Colonic mucosal hypoxia was visualized by
      pimonidazole staining. Both VEGF and PlGF were upregulated during acute colitis.
      In addition, compared with PlGF(+/+) controls, PlGF(-/-) mice showed a
      significant increase in weight loss and colonic shortening during both DSS and
      TNBS colitis. This correlated with enhanced colonocyte apoptosis, elevated
      colonic cytokine levels and increased histological damage score, but not with
      enhanced inflammatory cell infiltration (MPO activity). The increased morbidity
      of PlGF(-/-) mice during DSS colitis was preventable by adenovirus (Ad)-mediated
      overexpression of PlGF. After the administration of DSS, strongly reduced mucosal
      angiogenesis was observed in PlGF(-/-) mice compared with PlGF(+/+) mice. This
      was associated with an early increase in intestinal epithelial pimonidazole
      accumulation in PlGF(-/-) mice, suggesting a function of enhanced epithelial
      hypoxia in the observed differences between the two groups. In summary, our data
      show that the absence of PlGF strongly inhibits mucosal intestinal angiogenesis
      in acute colitis, which is associated with an early increase in intestinal
      epithelial hypoxia and aggravation of the course of the disease.

PMID- 20142802
TI  - 3D Telomere FISH defines LMP1-expressing Reed-Sternberg cells as end-stage cells
      with telomere-poor 'ghost' nuclei and very short telomeres.
AB  - In Epstein-Barr virus (EBV) negative Hodgkin's cell lines and classical EBV
      negative Hodgkin's lymphoma (HL), Reed-Sternberg cells (RS cells) represent end
      stage tumor cells, in which further nuclear division becomes impossible because
      of sustained telomere loss, shortening and aggregation. However, the three
      dimensional (3D) telomere organization in latent membrane protein 1 (LMP1)
      expressing RS cells of EBV-associated HL is not known. We performed a 3D telomere
      analysis after quantitative fluorescent in situ hybridization on 5 mum tissue
      sections on two LMP1-expressing HL cases and showed highly significant telomere
      shortening (P<0.0001) and formation of telomere aggregates in RS cells
      (P<0.0001), when compared with the mononuclear precursor Hodgkin cells (H cells).
      Telomere-poor or telomere-free 'ghost' nuclei were a regular finding in these RS
      cells. These nuclei and their telomere content strongly contrasted with the
      corona of surrounding lymphocytes showing numerous midsized telomere
      hybridization signals. Both H cells and RS cells of two EBV-negative HL cases
      analyzed in parallel showed 3D telomere patterns identical to those of LMP1
      expressing cases. As a major advance, our 3D nuclear imaging approach allows the
      visualization of hitherto unknown profound changes in the 3D nuclear telomere
      organization associated with the transition from LMP1-positive H cells to LMP1
      positive RS cells. We conclude that RS cells irrespective of LMP1 expression are
      end-stage tumor cells in which the extent of their inability to divide further is
      proportional to the increase of very short telomeres, telomere loss, aggregate
      formation and the generation of 'ghost' nuclei.

PMID- 20142803
TI  - Conditional overexpression of TGF-beta1 disrupts mouse salivary gland development
      and function.
AB  - Transforming growth factor-beta (TGF-beta) signaling is known to affect salivary
      gland physiology by influencing branching morphogenesis, regulating ECM
      deposition, and controlling immune homeostasis. To study the role of TGF-beta1 in
      the salivary gland, we created a transgenic mouse (beta1(glo)) that conditionally
      overexpresses active TGF-beta1 upon genomic recombination by Cre recombinase.
      beta1(glo) mice were bred with an MMTV (mouse mammary tumor virus)-Cre (MC)
      transgenic line that expresses the Cre recombinase predominantly in the secretory
      cells of both the mammary and salivary glands. Although most of the double
      positive (beta1(glo)/MC) pups die either in utero or just after birth, clear
      defects in salivary gland morphogenesis such as reduced branching and increased
      mesenchyme could be seen. Those beta1(glo)/MC mice that survived into adulthood,
      however, had hyposalivation due to salivary gland fibrosis and acinar atrophy.
      Increased TGF-beta signaling was observed in the salivary gland with elevated
      phosphorylation of Smad2 and concomitant increase in ECM deposition. In
      particular, aberrant TGF-beta1 overexpression caused salivary gland hypofunction
      in this mouse model because of the replacement of normal glandular parenchyma
      with interstitial fibrous tissue. These results further implicate TGF-beta in
      pathological cases of salivary gland inflammation and fibrosis that occur with
      chronic infections in the glands or with the autoimmune disease, Sjogren's
      syndrome, or with radiation therapy given to head-and-neck cancer patients.

PMID- 20142804
TI  - Hydrogen peroxide inhibits mTOR signaling by activation of AMPKalpha leading to
      apoptosis of neuronal cells.
AB  - Oxidative stress results in apoptosis of neuronal cells, leading to
      neurodegenerative disorders. However, the underlying molecular mechanism remains
      to be elucidated. Here, we show that hydrogen peroxide (H(2)O(2)), a major
      oxidant generated when oxidative stress occurs, induced apoptosis of neuronal
      cells (PC12 cells and primary murine neurons), by inhibiting the mammalian target
      of rapamycin (mTOR)-mediated phosphorylation of ribosomal p70 S6 kinase (S6K1)
      and eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). N-acetyl
      L-cysteine (NAC), a scavenger of reactive oxygen species (ROS), blocked H(2)O(2)
      inhibition of mTOR signaling. Ectopic expression of wild-type (wt) mTOR,
      constitutively active S6K1 or downregulation of 4E-BP1 partially prevented
      H(2)O(2) induction of apoptosis. Furthermore, we identified that H(2)O(2)
      induction of ROS inhibited the upstream kinases, Akt and phosphoinositide
      dependent kinase 1 (PDK1), but not the type I insulin-like growth factor receptor
      (IGFR), and activated the negative regulator, AMP-activated protein kinase alpha
      (AMPKalpha), but not the phosphatase and tensin homolog (PTEN) in the cells.
      Expression of a dominant negative AMPKalpha or downregulation of AMPKalpha1
      conferred partial resistance to H(2)O(2) inhibition of phosphorylation of S6K1
      and 4E-BP1, as well as cell viability, indicating that H(2)O(2) inhibition of
      mTOR signaling is at least in part through activation of AMPK. Our findings
      suggest that AMPK inhibitors may be exploited for prevention of H(2)O(2)-induced
      neurodegenerative diseases.

PMID- 20142805
TI  - The role of CD18 in the production and release of neutrophils from the bone
      marrow.
AB  - Neutrophil numbers must be tightly controlled to maintain host protection and
      prevent neutrophil-mediated tissue injury. CD18 deficiency leads to neutrophilia
      and myeloid hyperplasia in the bone marrow (BM). These studies examined the
      function of CD18 in regulating neutrophil production and determined whether the
      defects in neutrophil production that are observed in CD18 deficiency persist in
      the presence of wild-type (WT) leukocytes that confer host protection. Neutrophil
      production was evaluated in CD18(-/-) mice and lethally irradiated WT mice
      reconstituted with mixtures of CD18(-/-) and WT stem cells. Neutrophil kinetic
      studies suggest that CD18 may facilitate the release of the most mature
      neutrophils into the circulation. The proportion of CD18(-/-) neutrophils in
      chimeric animals was greater than the proportion of CD18(-/-) donor cells used to
      reconstitute the mice, and the percentage of CD18(-/-) leukocytes that were
      neutrophils was greater than for WT leukocytes, indicating that CD18 may regulate
      the lineage distribution of hematopoietic cells in the blood and BM. The
      proportion of Annexin V+ Gr-1+ cells in both the BM of chimeric animals and in
      vitro cultures of WT and CD18(-/-) hematopoietic stem cells was lower in CD18(-/
      ) than in WT cells, suggesting that CD18 modulates apoptosis. These data suggest
      that CD18 directly regulates neutrophil production, in part by limiting the
      survival of neutrophils and their precursors. Thus, the granulocytosis observed
      in CD18(-/-) mice and CD18-deficient patients is due to both defects in host
      defense and BM-intrinsic functions of CD18 in regulating neutrophil production.

PMID- 20142806
TI  - Disruption of sarcolemmal dystrophin and beta-dystroglycan may be a potential
      mechanism for myocardial dysfunction in severe sepsis.
AB  - Evidence from our laboratory has shown alterations in myocardial structure in
      severe sepsis/septic shock. The morphological alterations are heralded by
      sarcolemmal damage, characterized by increased plasma membrane permeability
      caused by oxidative damage to lipids and proteins. The critical importance of the
      dystrophin-glycoprotein complex (DGC) in maintaining sarcolemmal stability led us
      to hypothesize that loss of dystrophin and associated glycoproteins could be
      involved in early increased sarcolemmal permeability in experimentally induced
      septic cardiomyopathy. Male C57Bl/6 mice were subjected to sham operation and
      moderate (MSI) or severe (SSI) septic injury induced by cecal ligation and
      puncture (CLP). Using western blot and immunofluorescence, a downregulation of
      dystrophin and beta-dystroglycan expression in both severe and moderate injury
      could be observed in septic hearts. The immunofluorescent and protein amount
      expressions of laminin-alpha2 were similar in SSI and sham-operated hearts.
      Consonantly, the evaluation of plasma membrane permeability by intracellular
      albumin staining provided evidence of severe injury of the sarcolemma in SSI
      hearts, whereas antioxidant treatment significantly attenuated the loss of
      sarcolemmal dystrophin expression and the increased membrane permeability. This
      study offers novel and mechanistic data to clarify subcellular events in the
      pathogenesis of cardiac dysfunction in severe sepsis. The main finding was that
      severe sepsis leads to a marked reduction in membrane localization of dystrophin
      and beta-dystroglycan in septic cardiomyocytes, a process that may constitute a
      structural basis of sepsis-induced cardiac depression. In addition, increased
      sarcolemmal permeability suggests functional impairment of the DGC complex in
      cardiac myofibers. In vivo observation that antioxidant treatment significantly
      abrogated the loss of dystrophin expression and plasma membrane increased
      permeability supports the hypothesis that oxidative damage may mediate the loss
      of dystrophin and beta-dystroglycan in septic mice. These abnormal parameters
      emerge as therapeutic targets and their modulation may provide beneficial effects
      on future cardiovascular outcomes and mortality in sepsis.

PMID- 20142807
TI  - Low-dose paclitaxel ameliorates renal fibrosis in rat UUO model by inhibition of
      TGF-beta/Smad activity.
AB  - Transforming growth factor-beta (TGF-beta) has a pivotal function in the
      progression of renal fibrosis in a wide variety of renal diseases. Smad proteins
      have been identified to have an important function in regulating the expression
      of extracellular matrix (ECM) proteins through TGF-beta signaling pathway.
      Aberrant TGF-beta/Smad signaling can be modulated by stabilization of
      microtubules with paclitaxel. In this study, we investigated if paclitaxel can
      attenuate tubulointerstitial fibrosis in a rat model of unilateral ureteral
      obstruction (UUO). Rats in groups of six were subjected to UUO and received low
      dose intraperitoneal injection of paclitaxel (0.3 mg/kg) twice a week. They were
      killed at day 7 and 14 after UUO or Sham operation. TGF-beta signaling cascade
      and status of various ECM proteins were evaluated by RT-PCR, western blotting and
      immunohistochemical or immunofluorescence staining. The paclitaxel treatment
      markedly suppressed Smad2 and Smad3 phosphorylation. This was associated with
      attenuated expression of integrin-linked kinase, collagens I and III, fibronectin
      (FN) and alpha-smooth muscle actin, and a substantial decrease in renal fibrosis
      in animals that underwent UUO and received paclitaxel. These data indicate that
      the low-dose paclitaxel ameliorates renal tubulointerstitial fibrosis by
      modulating TGF-beta signaling, and thus, the paclitaxel may have some therapeutic
      value in humans.

PMID- 20142808
TI  - Cytopathology by optical methods: spectral cytopathology of the oral mucosa.
AB  - Spectral cytopathology (SCP) is a novel approach for diagnostic differentiation
      of disease in individual exfoliated cells. SCP is carried out by collecting
      information on each cell's biochemical composition through an infrared micro
      spectral measurement, followed by multivariate data analysis. Deviations from a
      cell's natural composition produce specific spectral patterns that are exclusive
      to the cause of the deviation or disease. These unique spectral patterns are
      reproducible and can be identified and used through multivariate statistical
      methods to detect cells compromised at the molecular level by dysplasia,
      neoplasia, or viral infection. In this proof of concept study, a benchmark for
      the sensitivity of SCP is established by classifying healthy oral squamous cells
      according to their anatomical origin in the oral cavity. Classification is
      achieved by spectrally detecting cells with unique protein expressions: for
      example, the squamous cells of the tongue are the only cell type in the oral
      cavity that have significant amounts of intracytoplasmic keratin, which allows
      them to be spectrally differentiated from other oral mucosa cells. Furthermore,
      thousands of cells from a number of clinical specimens were examined, among them
      were squamous cell carcinoma, malignancy-associated changes including reactive
      atypia, and infection by the herpes simplex virus. Owing to its sensitivity to
      molecular changes, SCP often can detect the onset of disease earlier than is
      currently possible by cytopathology visualization. As SCP is based on automated
      instrumentation and unsupervised software, it constitutes a diagnostic workup of
      medical samples devoid of bias and inconsistency. Therefore, SCP shows potential
      as a complementary tool in medical cytopathology.

PMID- 20142809
TI  - Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis
      associated with multifocal epithelial inflammation.
AB  - Bacterial infection has become a focus of attention in the pathogenesis of
      primary biliary cirrhosis (PBC). We earlier reported that the bacterial
      lipoteichoic acid was detected at the sites of inflammation around damaged bile
      ducts in the livers of PBC, and PBC patients' sera showed high titers against
      streptococcal histone-like protein. Here, we investigated whether chronic
      bacterial exposure could trigger PBC-like epithelial cell damage in normal mouse.
      BALB/c mice were repeatedly inoculated with various bacteria for 8 weeks. At 1
      week (Group 1) and 3, 4, or 20 months (long term; Group 2) after the final
      inoculation, mice were killed to obtain samples. In the livers of the
      Streptococcus intermedius (S.i.)-inoculated mice in Group 1, cellular
      infiltration was predominantly observed around the bile ducts over the hepatic
      parenchyma. In the S.i.-inoculated mice in Group 2, portal but not parenchymal
      inflammation was observed in the livers, and periductal cellular infiltrates were
      detected in the salivary glands. Both S.i.-inoculated Groups 1 and 2 BALB/c mice
      sera had antibodies against HuCCT1 biliary epithelial cells, anti-nuclear
      antibodies, and anti-gp210 antibodies, but not anti-mitochondrial antibodies.
      Immunoreactivity to histone-like DNA-binding protein of S.i. (S.i.-HLP) was
      detectable around the sites of chronic nonsuppurative destructive cholangitis in
      the portal area in the livers of both S.i.-inoculated Groups 1 and 2 BALB/c mice.
      Furthermore, anti-S.i.-HLP antibody bound to synthetic gp210 peptide, as well.
      Bacteria triggered PBC-like cholangitis, multifocal epithelial inflammation, and
      autoantibody production. Bacteria are likely involved in the pathogenesis of PBC
      and of associated multifocal epithelial inflammation.

PMID- 20142810
TI  - New treatments for chronic prostatitis/chronic pelvic pain syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition
      among men of a wide age range, with detrimental effects on quality of life. The
      etiology, pathogenesis, and optimal treatment of CP/CPPS remain unknown, although
      progress has been made in these domains in recent years. A wide variety of
      pharmacologic and nonpharmacologic therapies have been studied in clinical
      trials, but most have shown limited efficacy in symptom alleviation. CP/CPPS is
      increasingly viewed as a condition that involves variable degrees of neuropathic
      pain. Medications such as gabapentin, pregabalin, memantine, and tricyclic
      antidepressants are often used in other neuropathic pain conditions and,
      therefore, are considered potential treatments for CP/CPPS. Few studies of these
      agents in patients with CP/CPPS have been reported, but future clinical trials
      should help to determine their utility and to characterize the pathogenetic
      mechanisms of pain in CP/CPPS. Combining treatment trials with biomarker,
      genomic, and imaging studies, in addition to epidemiologic and symptom-based
      assessments, will maximize the ability to probe disease etiology and
      pathogenesis, as well as identify effective treatment.

PMID- 20142811
TI  - Sciatica: what the rheumatologist needs to know.
AB  - Sciatica is a set of symptoms rather than a specific diagnosis, and is caused by
      a herniated lumbar disc in the vast majority of cases. The most important symptom
      is lower limb pain radiating below the knee and into the foot and toes. The
      clinical course of acute sciatica is generally favorable, with most pain and
      related disability improving within 2-4 weeks with or without treatment.
      Diagnosis mainly involves history taking and physical examination. Imaging is
      warranted if there is evidence of an underlying pathology other than disc
      herniation, such as infection or malignancy, and in patients with severe symptoms
      that do not improve after 6-8 weeks of conservative treatment. MRI is the
      preferred imaging modality, as it can visualize soft tissues better than CT and
      does not expose the patient to ionizing radiation. Conservative treatment is
      generally the first-line option in patients with sciatica; however, the currently
      available evidence does not show any intervention--including a broad range of
      conservative and surgical approaches--to have clearly superior outcomes. Thus,
      patient preference seems to be an important factor in the clinical management of
      sciatica.

PMID- 20142812
TI  - Tumor necrosis factor blockade and the risk of viral infection.
AB  - Tumor necrosis factor (TNF) blockers are widely used to treat rheumatoid
      arthritis and other chronic inflammatory diseases. Many studies have demonstrated
      an increased risk of opportunistic infections such as tuberculosis and fungal
      infection in patients treated with TNF blockers, which is thought to be related
      to the primary role of TNF both in host defense and in the immune response.
      Little is known, however, about the association between TNF blockade and the
      development of viral infection. Owing to the critical role of TNF in the control
      of viral infection, depletion of this cytokine with TNF blockers could facilitate
      the development or reactivation of viral infection. A number of large
      observational studies have found an increased risk of herpes zoster in patients
      receiving TNF blockers for the treatment of rheumatoid arthritis. This Review
      draws attention to the risk of several viral infections, including HIV, varicella
      zoster virus, Epstein-Barr virus, cytomegalovirus, and human papillomavirus, in
      patients receiving TNF-blocking therapy for chronic inflammatory conditions. In
      addition, implications for clinical practice and possible preventative approaches
      are discussed.

PMID- 20142813
TI  - Sensors of the innate immune system: their link to rheumatic diseases.
AB  - Evidence strongly suggests that excessive or protracted signaling, or both, by
      cell-surface or intracellular innate immune receptors is central to the
      pathogenesis of most autoimmune and autoinflammatory rheumatic diseases. The
      initiation of aberrant innate and adaptive immune responses in autoimmune
      diseases can be triggered by microbes and, at times, by endogenous molecules-
      particularly nucleic acids and related immune complexes--under sterile
      conditions. By contrast, most autoinflammatory syndromes are generally dependent
      on germline or de novo gene mutations that cause or facilitate inflammasome
      assembly. The consequent production of proinflammatory cytokines, principally
      interferon-alpha/beta and tumor necrosis factor in autoimmune diseases, and
      interleukin-1beta in autoinflammatory diseases, leads to the creation of
      autoamplification feedback loops and chronicity of these syndromes. These
      findings have resulted in a critical reappraisal of pathogenetic mechanisms, and
      provide a basis for the development of novel diagnostic and therapeutic
      modalities for these diseases.

PMID- 20142814
TI  - Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins.
AB  - Rheumatoid arthritis (RA) is a prototypical immune-mediated inflammatory disease
      that is characterized by increased cardiovascular morbidity and mortality,
      independent of the traditional risk factors for cardiovascular disease. The
      chronic inflammatory state--a hallmark of RA--is considered to be a driving force
      for accelerated atherogenesis. Consequently, aggressive control of RA disease
      activity is thought to be instrumental for cardiovascular risk reduction.
      Currently, statin-mediated reduction of LDL-cholesterol levels is considered to
      be the cornerstone of cardiovascular disease prevention. In addition to their
      lipid-lowering capabilities, statins exert immunomodulatory effects, which could
      be of dual benefit in the treatment of RA. Guidelines on the reduction of
      cardiovascular risk in patients with RA are lacking, however, largely owing to
      the absence of data from randomized controlled trials. This Review focuses on the
      pathophysiology of cardiovascular events in RA, as well as the need to adjust
      cardiovascular risk engines to better-accommodate the impact of chronic
      inflammatory disease over and above the established risk factors to predict
      cardiovascular risk in patients with RA.

PMID- 20142815
TI  - Epidemiology and treatment of melanoma in elderly patients.
AB  - The number of melanoma cases in the elderly (>65 years) will rise over the coming
      decades, making it an important public health problem. Elderly white men are the
      demographic group who are at highest risk of being diagnosed with melanoma and of
      dying from this cancer. Among patients with melanoma, older age is recognized as
      an independent poor prognostic factor, but it remains unclear whether this
      relationship is due to a change in the biology of the disease with increasing
      patient age, declining host defenses, or both. Most elderly patients can have
      surgery to control locoregional disease, but might not be candidates for
      intensive biologic therapies for advanced melanoma because of comorbidities and
      inability to tolerate the adverse side effects of these treatments. Early
      detection remains an important strategy for the management of melanoma. Further
      research is needed to determine why older melanoma patients have a worse
      prognosis than their younger counterparts, even when matched for all other
      clinical and pathological predictors of survival outcomes.

PMID- 20142816
TI  - Microsatellite instability in colorectal cancer-the stable evidence.
AB  - Microsatellite instability (MSI) is the molecular fingerprint of a deficient
      mismatch repair system. Approximately 15% of colorectal cancers (CRC) display MSI
      owing either to epigenetic silencing of MLH1 or a germline mutation in one of the
      mismatch repair genes MLH1, MSH2, MSH6 or PMS2. Methods to detect MSI are well
      established and routinely incorporated into clinical practice. A clinical and
      molecular profile of MSI tumors has been described, leading to the concept of an
      MSI phenotype in CRC. Studies have confirmed that MSI tumors have a better
      prognosis than microsatellite stable CRC, but MSI cancers do not necessarily have
      the same response to the chemotherapeutic strategies used to treat microsatellite
      stable tumors. Specifically, stage II MSI tumors might not benefit from 5
      fluorouracil-based adjuvant chemotherapy regimens. New data suggest possible
      advantages of irinotecan-based regimens, but these findings require further
      clarification. Characterization of the molecular basis of MSI in CRC is underway
      and initial results show that mutations in genes encoding kinases and candidate
      genes with microsatellite tracts are over-represented in MSI tumors.
      Transcriptome expression profiles of MSI tumors and systems biology approaches
      are providing the opportunity to develop targeted therapeutics for MSI CRC.

PMID- 20142818
TI  - Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic
      states in adulthood: implication in neurodevelopmental hypothesis for
      schizophrenia.
AB  - Neuregulin-1 (NRG1) is implicated in the etiology or pathology of schizophrenia,
      although its biological roles in this illness are not fully understood. Human
      midbrain dopaminergic neurons highly express NRG1 receptors (ErbB4). To test its
      neuropathological role in the neurodevelopmental hypothesis of schizophrenia, we
      administered type-1 NRG1 protein to neonatal mice and evaluated the immediate and
      subsequent effects on dopaminergic neurons and their associated behaviors.
      Peripheral NRG1 administration activated midbrain ErbB4 and elevated the
      expression, phosphorylation and enzyme activity of tyrosine hydroxylase (TH),
      which ultimately increased dopamine levels. The hyperdopaminergic state was
      sustained in the medial prefrontal cortex after puberty. There were marked
      increases in dopaminergic terminals and TH levels. In agreement, higher amounts
      of dopamine were released from this brain region of NRG1-treated mice following
      high potassium stimulation. Furthermore, NRG1-treated mice exhibited behavioral
      impairments in prepulse inhibition, latent inhibition, social behaviors and
      hypersensitivity to methamphetamine. However, there were no gross abnormalities
      in brain structures or other phenotypic features of neurons and glial cells.
      Collectively, our findings provide novel insights into neurotrophic contribution
      of NRG1 to dopaminergic maldevelopment and schizophrenia pathogenesis.

PMID- 20142817
TI  - Sudden cardiac death: epidemiology and risk factors.
AB  - Sudden cardiac death (SCD) is an important public-health problem with multiple
      etiologies, risk factors, and changing temporal trends. Substantial progress has
      been made over the past few decades in identifying markers that confer increased
      SCD risk at the population level. However, the quest for predicting the high-risk
      individual who could be a candidate for an implantable cardioverter
      defibrillator, or other therapy, continues. In this article, we review the
      incidence, temporal trends, and triggers of SCD, and its demographic, clinical,
      and genetic risk factors. We also discuss the available evidence supporting the
      use of public-access defibrillators.

PMID- 20142819
TI  - Endophenotype: a conceptual analysis.
AB  - This paper provides a conceptual analysis of the endophenotype (EP) construct
      that is having an increasing role in genetic strategies for unraveling the
      etiology of psychiatric disorders (PDs). We make six major points illustrated
      through the method of path analysis. First, it is important to distinguish
      between mediational and liability-index (or 'risk indicator') models for EP, as
      only the former requires genetic risk for PD to pass through EP. Second, the
      relative reliability of EP and PD can have a critical role in the interpretation
      of results. Ignoring them can lead to substantial errors of inference. Third, we
      need to consider bidirectional relationships between an EP and a PD, and the
      possibility that genetic effects on PD are only partially mediated by EP. Fourth,
      EP models typically assume that all genetic effects that have an impact on EP
      also alter risk for PD. However, among the genetic influences on EP and PD, it is
      also plausible that some will influence only EP, some only PD and some both.
      Fifth, we should also consider models incorporating multiple EPs and PDs, which
      can be well captured by multivariate genetic methods. Sixth, EPs may also reflect
      the impact of the environment on risk for PDs. The EP concept has important
      potential lessons for etiological research in PDs that can be optimized by
      considering it as a special case of a broader set of multivariate genetic models,
      which can be fitted using currently available methodology.

PMID- 20142821
TI  - Decreased blood-brain leptin transfer in an ovine model of obesity and weight
      loss: resolving the cause of leptin resistance.
AB  - OBJECTIVE: Hypothalamic resistance to the anorexigenic actions of the peripheral
      adipostat hormone leptin is characteristic of obesity. Here, we use an obese
      animal model of similar body weight to that of the human to test in vivo whether
      leptin resistance is due to decreased blood-brain leptin transport or intra
      hypothalamic insensitivity, and whether sensitivity to leptin is restored by
      weight loss. For 40 weeks, adult sheep surgically prepared with intra
      cerebroventricular (ICV) cannulae were given a complete natural diet ad libitum
      ('Obese' group) or in restricted quantities ('Lean' group), and then the dietary
      amounts were reversed for 16 weeks until mean group body weights converged
      ('Slimmers' and 'Fatteners', respectively). RESULTS: ICV leptin injection (0.5
      mg) at 8-week intervals acutely decreased voluntary food intake by approximately
      35% in the 'Obese' group on each occasion and in 'Slimmers' and 'Fatteners' at
      the end, providing no evidence of intra-hypothalamic insensitivity. The ratio
      between endogenous leptin concentrations in ventricular cerebrospinal fluid (CSF)
      and peripheral blood decreased with increasing leptinaemia in 'Obese' sheep,
      indicating decreased efficiency of blood-brain leptin transport, whereas leptin
      concentrations remained low and the CSF:blood ratio remained high in 'Lean'
      sheep. Compared with 'Fatteners' of similar body weight, 'Slimmers' were
      hypoleptinaemic, but their CSF:blood leptin concentration ratio remained low.
      Thus, the obesity-induced impairment of leptin blood-brain transport was
      sustained despite an approximately 15% weight loss. CONCLUSION: These results
      support the hypothesis that central resistance to leptin in obesity with
      associated peripheral hyperleptinaemia is attributable to decreased efficiency of
      leptin transport into the brain and not to intra-hypothalamic leptin
      insensitivity. However, leptin transport efficiency is not restored after weight
      loss by caloric restriction despite the prevailing hypoleptinaemia.

PMID- 20142820
TI  - Translational research in bipolar disorder: emerging insights from genetically
      based models.
AB  - Bipolar disorder (BPD) is characterized by vulnerability to episodic depression
      and mania and spontaneous cycling. Because of marked advances in candidate-gene
      and genome-wide association studies, the list of risk genes for BPD is growing
      rapidly, creating an unprecedented opportunity to understand the pathophysiology
      of BPD and to develop novel therapeutics for its treatment. However, genetic
      findings are associated with major unresolved issues, including whether and how
      risk variance leads to behavioral abnormalities. Although animal studies are key
      to resolving these issues, consensus is needed regarding how to define and
      monitor phenotypes related to mania, depression and mood swing vulnerability in
      genetically manipulated rodents. In this study we discuss multiple facets of this
      challenging area, including theoretical considerations, available tests,
      limitations associated with rodent behavioral modeling and promising molecular
      behavioral findings. These include CLOCK, glycogen synthase kinase 3beta (GSK
      3beta), glutamate receptor 6 (GluR6), extracellular signal-regulated kinase-1
      (ERK1), p11 (or S100A10), vesicular monoamine transporter 2 (VMAT2 or SLC18A2),
      glucocorticoid receptors (GRs), Bcl-2-associated athanogene-1 (BAG1) and
      mitochondrial DNA polymerase-gamma (POLG). Some mutant rodent strains show
      behavioral clusters or activity patterns that cross-species phenocopy
      objective/observable facets of mood syndromes, and changes in these clustered
      behaviors can be used as outcome measures in genetic-behavioral research in BPD.

PMID- 20142822
TI  - Use of the cellular model of body composition to describe changes in body water
      compartments after total fasting, very low calorie diet and low calorie diet in
      obese men.
AB  - INTRODUCTION: The cellular model of body composition divides the body in body
      cell mass (BCM), extracellular solids and extracellular fluids. This model has
      been infrequently applied for the evaluation of weight loss (WL) programmes.
      OBJECTIVES: (1) To assess changes in body compartments in obese men undergoing
      fasting, very low calorie diet (VLCD) and low calorie diet (LCD); (2) to evaluate
      two cellular models for the determination of changes in BCM, fat mass (FM) and
      body fluids. MATERIALS AND METHODS: Three groups of six, obese men participated
      in a total fast (F) for 6 days, a VLCD (2.5 MJ per day) for 3 weeks or an LCD
      (5.2 MJ per day) for 6 weeks. Body composition was measured at baseline and after
      small ( approximately 5%) and moderate ( approximately 10%) WL. FM was measured
      using a four-compartment model. Total body water (TBW) and extracellular water
      (ECW) were, respectively, measured by deuterium and sodium bromide dilution and
      intracellular water (ICW) calculated by difference. Two cellular models were used
      to measure BCM, FM and body fluids distribution. RESULTS: After about 5%WL
      changes in TBW were F=-3.2+/-1.2 kg (P<0.01), VLCD=-1.2+/-0.6 kg (P<0.01), LCD=
      0.3+/-0.9 kg(n.s.). The contribution of TBW to total body mass loss was
      indirectly associated with FM loss. ECW increased during fasting (+1.5+/-3.1 kg,
      n.s.), decreased during the VLCD (-2.0+/-1.5 kg, P<0.05) and remained unchanged
      at the end of the LCD (-0.3+/-1.6 kg, n.s.). ICW significantly decreased during
      fasting (-4.7+/-3.9 kg, P<0.05) but did not change in the LCD and VLCD groups.
      The loss of BCM was more significant in the fasting group and it was directly
      associated with changes in ICW. CONCLUSIONS: After a 6-day period of fasting we
      observed more ICW losses and less fat mobilization compared with VLCD and LCD.
      The cellular model of body composition is suitable for the characterization of
      changes in body fluids distribution during WL.

PMID- 20142823
TI  - Effects of multivitamin and mineral supplementation on adiposity, energy
      expenditure and lipid profiles in obese Chinese women.
AB  - BACKGROUND: Obese individuals are more likely to have either lower blood
      concentrations or lower bioavailability of minerals and/or vitamins. However,
      there are limited data on the effects of nutritional supplementation on body
      weight (BW) control, energy homeostasis and lipid metabolism in obese subjects.
      OBJECTIVE: The purpose of this study is to evaluate the effects of
      supplementation with multivitamin and multimineral on adiposity, energy
      expenditure and lipid profiles in obese Chinese women. DESIGN: A total of 96
      obese Chinese women (body mass index (BMI) 28 kg m(-2)) aged 18-55 years
      participated in a 26-week randomized, double-blind, placebo-controlled
      intervention study. Subjects were randomized into three groups, receiving either
      one tablet of multivitamin and mineral supplement (MMS), or calcium 162 mg
      (Calcium) or identical placebo daily during the study period. BW, BMI, waist
      circumference (WC), fat mass (FM), fat-free mass, resting energy expenditure
      (REE), respiratory quotient (RQ), blood pressure, fasting plasma glucose and
      serum insulin, total cholesterol (TC), low- and high-density lipoprotein
      cholesterol (LDL-C and HDL-C) and triglycerides (TGs) were measured at baseline
      and 26 weeks. RESULTS: A total of 87 subjects completed the study. After 26
      weeks, compared with the placebo group, the MMS group had significantly lower BW,
      BMI, FM, TC and LDL-C, significantly higher REE and HDL-C, as well as a
      borderline significant trend of lower RQ (P=0.053) and WC (P=0.071). The calcium
      group also had significantly higher HDL-C and lower LDL-C levels compared with
      the placebo group. CONCLUSION: The results suggest that, in obese individuals,
      multivitamin and mineral supplementation could reduce BW and fatness and improve
      serum lipid profiles, possibly through increased energy expenditure and fat
      oxidation. Supplementation of calcium alone (162 mg per day) only improved lipid
      profiles.

PMID- 20142824
TI  - Association of body mass index with Short-Form 36 physical and mental component
      summary scores in a multiethnic Asian population.
AB  - OBJECTIVES: To investigate the association between body mass index (BMI) and
      physical and mental health-related quality of life (HRQoL) in a multiethnic Asian
      population in Singapore, and explore whether there were gender and ethnic
      differences in this association. METHODS: We conducted cross-sectional analyses
      using data from 5027 Chinese, Malay and Indian participants (2403 men and 2624
      women) aged 24-95 years. These subjects were from four previous cross-sectional
      surveys carried out in Singapore (from 1982 to 1998) who attended a follow-up
      examination (including both a questionnaire and a clinic examination) between
      2004 and 2007, during which HRQoL was assessed. Participants were classified as
      underweight (<18.5 kg m(-2)), normal weight (18.5 to <23 kg m(-2)), overweight
      (23 to <25 kg m(-2)), moderate obese (25 to <30 kg m(-2)) and severe obese
      (>or=30 kg m(-2)). HRQoL was measured using the Short-Form 36-item questionnaire
      (SF-36) physical component summary score (PCS) and mental component summary score
      (MCS). Linear regressions with and without adjusting for other covariates were
      used to evaluate the association between BMI and SF-36 PCS and MCS. RESULTS:
      Compared with participants with normal weight, moderate or severe obesity was
      associated with 0.8 points (95% confidence interval (CI): -1.5 to -0.1, P=0.03)
      and 2.1 points lower PCS (95% CI: -3.1 to -0.1, P<0.001), respectively, after
      adjustment for sociodemographic variables, family functioning measure scores and
      the presence of chronic diseases. These associations were greater in women than
      in men. In contrast, being underweight was associated with 1.3 points lower MCS
      (95% CI: -2.3 to -0.3, P=0.014). CONCLUSIONS: In this study (one of few studies
      in the Asia-Pacific region), obesity was associated with lower PCS and the effect
      was modified by gender but not ethnicity, such that the association was greater
      in women than in men. However, obesity was not associated with MCS. Underweight
      was associated with reduced MCS but not PCS.

PMID- 20142825
TI  - Visceral adipose tissue and inflammation correlate with elevated liver tests in a
      cohort of overweight and obese patients.
AB  - OBJECTIVE: To study the relationship between elevated liver tests and high
      sensitive C-reactive protein (hs-CRP), as potential markers of liver inflammation
      and non-alcoholic steatohepatitis (NASH), with anthropometric and laboratory
      parameters in overweight patients, especially the relationship with visceral
      adipose tissue (VAT). METHODS: Patients presenting to the obesity clinic were
      prospectively included. Detailed anthropometry, computed tomography (CT)-measured
      VAT, liver tests (aspartate transaminase (AST), alanine transaminase (ALT),
      alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT)) and hs-CRP were
      assessed, along with an extended series of biochemical parameters. RESULTS: All
      480 patients (gender distribution male (M)/female (F) (10/90%)) with complete
      data were included. Mean age was 39+/-13 years, mean BMI 34.5+/-6.0 kg m(-2). In
      37.3% of the patients one or more of the liver tests were elevated. VAT was
      positively related to AST (r=0.18, P<0.001), ALT (r=0.29, P<0.001), ALP (r=0.16,
      P<0.01) and GGT (r=0.39, P<0.001). Comparing subjects with high (VAT>or=113
      cm(2)) vs low (VAT<113 cm(2)) VAT levels, significant differences were noted for
      AST (26+/-12 vs 24+/-12 U l(-1), P=0.003), ALT (37+/-21 vs 31+/-21 U l(-1),
      P<0.001), ALP (76+/-20 vs 71+/-18 U l(-1), P=0.008), GGT (33+/-20 vs 25+/-15 U l(
      1), P<0.001) and hs-CRP (0.62+/-0.43 vs 0.52+/-0.48 mg dl(-1), P<0.001). After
      correction for BMI the difference in AST and ALP between the high vs low VAT
      group disappeared. The differences for ALT and GGT remained significant (P=0.008
      and P<0.001 respectively). After correction for hs-CRP the four different liver
      tests remained significantly higher in the high VAT group. A stepwise multiple
      regression analysis revealed that every single liver test has his own most
      important determinant; VAT and hs-CRP for AST, insulin resistance calculated with
      homeostasis model assessment (HOMA-IR) and hs-CRP for ALT and ALP, and
      triglycerides and VAT for GGT. CONCLUSION: In overweight and obese patients,
      liver tests, especially ALT and GGT, are associated with visceral fat mass. After
      correction for BMI and hs-CRP, ALT and GGT are significantly higher in patients
      with increased VAT, thereby supporting evidence for a potential key role of VAT
      in the pathogenesis of non-alcoholic fatty liver disease (NAFLD).

PMID- 20142826
TI  - Slc27a2 expression in peripheral blood mononuclear cells as a molecular marker
      for overweight development.
AB  - BACKGROUND: Peripheral blood mononuclear cells (PBMC) can be collected easily and
      repeatedly. Their potential use to reflect the individual's biological status is
      increasingly explored. Obesity is becoming the most common health problem of the
      21st century, being dietary intake an important determinant of this pathology and
      numerous chronic health conditions. OBJECTIVE: The aim of this study is to
      identify PBMC genes involved in energy homeostasis, which could be good markers
      of overweight development. DESIGN: Using whole-genome microarray analysis, we
      evaluated the gene expression in PBMC of normoweight and diet-induced obese
      (cafeteria-fed) Wistar rats. RESULTS: Microarray analysis showed 566 genes
      differentially expressed between normoweight and cafeteria-fed rats. Of these, 35
      genes were particularly involved in energy homeostasis. The gene with the biggest
      fold change was the 'solute carrier family 27 (fatty acid transporter), member 2'
      (slc27a2), which is implicated in lipid biosynthesis and fatty acid degradation.
      Scl27a2 was 33-fold overexpressed in cafeteria-fed rats compared with normoweight
      rats. This result was confirmed by quantitative PCR, although the overexpression
      was smaller (sixfold). Moreover, the increase in slc27a2 expression in PBMC of
      cafeteria-fed rats from 2 to 6 months of age paralleled the increase in body
      weight. CONCLUSION: The progressive overexpression of slc27a2 in PBMC of
      cafeteria-fed rats as the body weight increases suggests this gene as an early
      marker of overweight development related to the intake of a hyperlipidic diet.

PMID- 20142827
TI  - Thermogenic ingredients and body weight regulation.
AB  - The global prevalence of obesity has increased considerably in the last decade.
      Tools for obesity management, including consumption of caffeine, capsaicin and
      different teas such as green, white and oolong tea, have been proposed as
      strategies for weight loss and weight maintenance, as they may increase energy
      expenditure (4-5%), fat oxidation (10-16%) and have been proposed to counteract
      the decrease in metabolic rate that is present during weight loss. Daily
      increases in thermogenesis of approximately 300-400 kJ can eventually lead to
      substantial weight loss. However, it becomes clearer that certain conditions have
      to be met before thermogenic ingredients yield an effect, as intra-variability
      with respect to body weight regulation has been shown between subjects.
      Furthermore, the sympathetic nervous system is involved in the regulation of
      lipolysis, and the sympathetic innervation of white adipose tissue may have an
      important role in the regulation of total body fat in general. Taken together,
      these functional ingredients have the potential to produce significant effects on
      metabolic targets such as satiety, thermogenesis and fat oxidation. A significant
      clinical outcome may sometimes appear straightforward and may also depend very
      strongly on full compliance of subjects. Nevertheless, thermogenic ingredients
      may be considered as functional agents that could help in preventing a positive
      energy balance and obesity.

PMID- 20142828
TI  - Is childcare associated with the risk of overweight and obesity in the early
      years? Findings from the UK Millennium Cohort Study.
AB  - BACKGROUND: A recent assessment of childcare in OECD (Organisation for Economic
      Co-operation and Development) countries highlighted the potential for childcare
      to widen inequalities. Although childcare offers a potential setting for obesity
      prevention, little research has analysed the association between childcare and
      overweight, particularly in different socio-economic groups. OBJECTIVES: Our
      primary objective was to explore the association between childcare and overweight
      (including obesity), both overall and by socio-economic background, in a
      contemporary UK cohort of children at age 3 years (N=12 354). Our secondary
      objective was to explore infant feeding as a potential mediator between childcare
      in infancy and overweight at age 3 years. RESULTS: After controlling for
      confounders, children who were cared for in informal childcare (75% grandparents)
      between the age of 9 months and 3 years were more likely to be overweight than
      those cared for only by a parent (adjusted risk ratio (aRR)=1.15, 95% confidence
      interval (CI) 1.04-1.27), particularly if they were in full-time childcare
      (aRR=1.34, 95% CI 1.15-1.57). When stratifying by socio-economic background, the
      increased risk of overweight in informal childcare (compared with parental care)
      was limited to children from more advantaged groups: those whose mother was from
      a managerial or professional background (aRR=1.23, 95% CI 1.02-1.47), had a
      degree (RR=1.43, 95% CI 1.13-1.83) or lived in a couple household (RR=1.18, 95%
      CI 1.06-1.32). There was no association between formal childcare and overweight.
      Infant feeding did not mediate the association between childcare use in infancy
      and overweight at age 3 years. CONCLUSIONS: Children from more advantaged
      families who use informal childcare are at increased risk of overweight. The UK
      government's drive to support parents into paid employment should be accompanied
      by health-related information and support for both informal and formal carers. As
      the majority of informal carers were grandparents, the recent government
      announcement to provide grandparents with National Insurance credits for caring
      for grandchildren provides a potential opportunity for health promotion.

PMID- 20142829
TI  - Obesity, overweight and liver disease in the Midspan prospective cohort studies.
AB  - OBJECTIVES: To analyse the relationship between body mass index (BMI) and liver
      disease in men and women. DESIGN: The Midspan prospective cohort studies.
      PARTICIPANTS: The three studies were: Main study, screened in 1965-1968,
      workplaces across Scotland, the general population of the island of Tiree and
      mainland relatives; Collaborative study, conducted from 1970 to 1973, 27
      workplaces in Glasgow, Clydebank and Grangemouth; Renfrew/Paisley general
      population study, screened in 1972-1976. After exclusions there were 16 522 men
      and 10 216 women, grouped by BMI into under/normal weight (< 25 kg m(-2)),
      overweight (25 to < 30 kg m(-2)) and obese (>or=30 kg m(-2)). MEASUREMENTS:
      Relative rates (RRs) of liver disease mortality, subdivided into liver cancer and
      all other liver disease, by BMI category and per s.d. increase in BMI, followed
      up to end 2007. RRs of liver disease from any diagnosis on the death certificate,
      hospital discharge records or cancer registrations (Collaborative and
      Renfrew/Paisley studies only 13 027 men and 9328 women). Analyses adjusted for
      age and study, then other confounders. RESULTS: In total, 146 men (0.9%) and 61
      women (0.6%) died of liver disease as main cause. There were strong associations
      of BMI with liver disease mortality in men (RR per s.d. increase in BMI=1.41 (95%
      confidence interval 1.21-1.65)). Obese men had more than three times the rate of
      liver disease mortality than under/normal weight men. Adjustment for other risk
      factors had very little effect. No substantial or robust associations were
      observed in women. In all, 325 men (2.5%) and 155 women (1.7%) had liver disease
      established from any source. Similar positive associations were observed for men,
      and there was evidence of a relationship in women. CONCLUSIONS: BMI is related to
      liver disease, although not to liver disease mortality in women. The current rise
      in overweight and obesity may lead to a continuing epidemic of liver disease.

PMID- 20142830
TI  - Review of the efficacy and safety of transanal irrigation for neurogenic bowel
      dysfunction.
AB  - STUDY DESIGN: Neurogenic bowel dysfunction (NBD) is a common occurrence after
      spinal cord injury (SCI) and in patients with spina bifida or multiple sclerosis.
      The impact of NBD on well-being is considerable, affecting both physical and
      psychological aspects of quality of life. Transanal irrigation (TAI) of the colon
      promotes the evacuation of faeces by introducing water into the colon and rectum
      through a catheter inserted into the anus. Regular and controlled evacuation in
      this manner aims at preventing both constipation and faecal soiling. OBJECTIVES:
      The aim of this study was to review current evidence for the efficacy and safety
      of TAI in patients with NBD. MATERIALS AND METHODS: A literature search was
      conducted in PubMed. All identified papers were assessed for relevance based on
      the title and abstract; this yielded 23 studies that were considered to be of
      direct relevance to the topic of the review. RESULTS: A multicentre, randomized,
      controlled trial has supported observational reports in demonstrating that TAI
      offers significant benefits over conservative bowel management in patients with
      SCI, in terms of managing constipation and faecal incontinence, reducing NBD
      symptoms and improving quality of life. Among other populations with NBD, TAI
      shows the greatest promise in children with spina bifida; however, further
      investigation is required. The overall safety profile of TAI is good, with few,
      and rare, adverse effects. CONCLUSIONS: Building on the positive data reported
      for patients with SCI, continued evaluation in the clinical trial setting is
      required to further define the utility of TAI in other populations with NBD.

PMID- 20142831
TI  - The clinical study of repairing cauda equina fibres with fibrin glue after lumbar
      fracture and dislocation.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: To study the outcome of repair
      of cauda equina fibres with fibrin glue after lumbar fracture and/or dislocation.
      METHODS: Seven acute cases and one chronic case of L2 or L3 fracture and/or
      dislocation complicated with complete cauda equina injury were selected. Sural
      nerve or ventral roots of injured cauda equina were chosen to repair the motor
      cauda equina fibres with fibrin glue after open reduction and internal fixation
      of the unstable vertebrae. The functional recovery after surgery was observed.
      RESULTS: Recovery of the strength of thigh muscles (iliopsoas, quadriceps
      femoris, gluteus maximus, adductors) was observed in all seven acutely injured
      patients (t=3.74, P<0.05), but not in the chronic one. Neither recovery of leg
      muscles nor sensation of the lower extremities was observed in any case.
      CONCLUSIONS: The cauda equina ventral roots injured after lumbar fracture and/or
      dislocation can be repaired with fibrin glue and motor recovery is expected.

PMID- 20142832
TI  - Community reintegration of spinal cord-injured patients in rural south India.
AB  - STUDY DESIGN: Cross sectional follow-sup survey. OBJECTIVE: To ascertain the
      factors influencing community reintegration, of individuals with spinal cord
      injury living in rural environment, and to suggest measures to enhance community
      participation. SETTING: Bangalore, Karnataka, India. METHODS: Thirty-five
      individuals who were admitted under Physical Medicine and Rehabilitation
      Department of St Johns Medical College Hospital and rehabilitated to their
      functional level based on their level of injury; individuals living in rural
      environment were included in the study. The study was conducted by means of a
      standardized questionnaire and environmental and home assessments carried out
      during follow-up home visits after 12 months of discharge from the hospital. The
      main outcome measures were Craig Handicap Assessment and Reporting Technique
      (CHART) and Craig Hospital Inventory of Environmental Factors (CHIEF). The home
      visits and assessments were carried out by a rehabilitation team, which consisted
      of community-based rehabilitation worker, medico-social worker, physiotherapist
      and occupational therapist, and headed by a physiatrist. RESULTS: The findings of
      the study indicate a general decline in community re integration in terms of
      physical independence, mobility, occupation and social integration. Mobility
      issues were the greatest perceived barrier and economic issues also significantly
      influenced the community participation. CONCLUSION: Our study showed significant
      decline in community reintegration in subjects living in rural south India.
      Architectural and environmental barriers, poor socio-economic status and
      comorbidities significantly affected the level of community participation.

PMID- 20142833
TI  - Response to the letter to the editor by J Silver 'Re: Case report: a fatal
      metastasis of Klebsiella pneumonia of the lungs'.

PMID- 20142835
TI  - Potent anti-tumor responses to immunization with dendritic cells loaded with
      tumor tissue and an NKT cell ligand.
AB  - Cancer immunotherapy is well tolerated and specific, but its efficacy remains
      variable. To enhance anti-tumor CD8(+) T-cell responses induced by immunization
      with antigen-loaded dendritic cells (DCs), we explored the impact of eliciting a
      potent source of T-cell help from activated invariant natural killer (NK)-like T
      cells (iNKT cells) using the specific glycolipid ligand alpha-galactosylceramide
      (alpha-GalCer). As cytokines released by iNKT cells may drive proliferation of
      CD4(+)CD25(+) regulatory T cells (Tregs), we assessed this immunization strategy
      in animals treated with anti-CD25 antibody to inactivate Treg function. Combining
      DC immunization with iNKT cell activation was found to significantly enhance anti
      tumor activity, which was improved further by the prior inactivation of Tregs.
      The improved anti-tumor activity with Treg inactivation was associated with a
      prolonged proliferative burst of responding CD8(+) T cells. We could find no
      evidence that inclusion of alpha-GalCer in the vaccine enhanced Treg numbers, or
      that the 'helper' function of iNKT cells was improved in the absence of Treg
      activity. Rather, the two activities appeared to act independently to improve the
      tumor-specific T-cell response. Inactivating regulatory T cells and eliciting
      iNKT cell activation are therefore two useful strategies that can be used in
      combination to improve anti-tumor immunization with antigen-loaded DCs.

PMID- 20142836
TI  - Influenza viruses differ in ability to infect macrophages and to induce a local
      inflammatory response following intraperitoneal injection of mice.
AB  - Strains of influenza A virus show marked differences in their ability to infect
      murine macrophages (MPhi) such that strain A/PR/8/34 (PR8; H1N1) infects MPhi
      poorly while strain BJx109 (H3N2) infects MPhi to high levels. Given the central
      role of MPhi in initiating and regulating inflammatory responses, we hypothesized
      that virus strains that infect MPhi poorly may also be poor at initiating
      inflammatory responses. Studies to compare the inflammatory response of mice
      after intranasal inoculation with either BJx109 or PR8 were confounded by the
      rapid growth of the PR8 virus in lung tissues. Consequently, we have
      characterized the cellular inflammatory response following inoculation into the
      peritoneal cavity, as influenza viruses do not replicate at this site. Herein, we
      report marked differences in the local inflammatory response to BJx109 or PR8 in
      the peritoneal cavity with strain PR8 being particularly poor in its ability to
      recruit and activate peritoneal leukocytes, including NK cells and MPhi. In vitro
      BJx109, but not PR8, stimulated release of high levels of type I IFNs and TNF
      alpha from PEC MPhi, and treatment of mice with neutralizing antibodies to either
      cytokine inhibited the ability of BJx109 to recruit and activate NK cells and
      MPhis in the peritoneal cavity. Together, these data suggest that the ability of
      influenza virus strains to infect MPhi and stimulate cytokine release is an
      important factor governing the nature of the acute inflammatory response.

PMID- 20142837
TI  - Naturally occurring tumor-specific CD8+ T-cell precursors in individuals with and
      without cancer.
AB  - Boosting pre-existing, naturally occurring cytolytic CD8(+) T-cell (CTLs)
      responses directed against class-I MHC-restricted peptides of tumor antigens,
      represents a primary goal of cancer immunotherapy. The number of pre-existing
      antitumor CTLs and their impaired function has been incriminated as the most
      likely candidates for the reduced clinical efficacy of these trials. This study
      was scheduled to determine possible differences in the frequency and the function
      of naturally occurring CTL precursors (pCTLs) against multiple peptides derived
      from the cancer-testis antigens MAGE-A1 and MAGE-A3, and the overexpressed
      antigen hTERT, in newly diagnosed lung cancer patients as compared with aged
      matched healthy individuals. The cumulative frequency of circulating peptide
      specific pCTLs was found significantly higher in the cancer patients, varied
      widely and was not affected by radiotherapy and chemotherapy. Furthermore, this
      frequency was greatly different between the various tumor-antigen peptides. Under
      the light of recent evidence provided from animal models, these results indicate
      that the peptide-specific pCTL frequency might represent an important determinant
      for the fate of cancer immunotherapy. In addition, our results show that tumor
      specific pCTLs of cancer patients can present functional differences regarding
      their proliferative capacity, intensity of multimer staining and lytic capacity,
      when compared with those of healthy individuals. Hence, our findings could have
      an important role for the design of improved immunotherapeutic approaches for
      lung cancer.

PMID- 20142838
TI  - Killer T cells not so deadly in HIV.

PMID- 20142834
TI  - Establishing, maintaining and modifying DNA methylation patterns in plants and
      animals.
AB  - Cytosine DNA methylation is a stable epigenetic mark that is crucial for diverse
      biological processes, including gene and transposon silencing, imprinting and X
      chromosome inactivation. Recent findings in plants and animals have greatly
      increased our understanding of the pathways used to accurately target, maintain
      and modify patterns of DNA methylation and have revealed unanticipated
      mechanistic similarities between these organisms. Key roles have emerged for
      small RNAs, proteins with domains that bind methylated DNA and DNA glycosylases
      in these processes. Drawing on insights from both plants and animals should
      deepen our understanding of the regulation and biological significance of DNA
      methylation.

PMID- 20142839
TI  - Foxp3 induction in human and murine thymus precedes the CD4+ CD8+ stage but
      requires early T-cell receptor expression.
AB  - The thymus generates a T-cell lineage dedicated to immune regulation, 'naturally
      occurring' regulatory T cells, best specified by the forkhead family
      transcription factor Foxp3. Here, we have conducted a parallel study in humans
      and mice where we have dissected the earliest stages of Foxp3 induction during
      thymocyte development. By analyzing a large collection of 21 human thymuses we
      show that Foxp3 can be consistently detected in CD4 immature single positive
      thymocytes that precede the CD4(+)CD8(+) (double positive, DP) stage. The reduced
      levels of CD3 expression found at this stage of human thymocyte development raise
      the question of TCR (T-cell receptor) requirement for Foxp3 induction. We further
      show that, in mice, Foxp3 expression was also detected in pre-DP thymocytes of
      TCRalpha-sufficient but not in TCRalpha-deficient animals, genetically showing
      the TCR dependence of Foxp3 expression at pre-DP stages of T-cell development.

PMID- 20142840
TI  - Heritable and non-genetic factors as variables of pharmacologic phenotypes in
      lymphoblastoid cell lines.
AB  - Publicly available genetic and expression data on lymphoblastoid cell lines
      (LCLs) make them a unique resource for understanding the genetic underpinnings of
      pharmacological outcomes and disease. LCLs have been used for pharmacogenomic
      discovery and validation of clinical findings associated with drug response.
      However, variation in cellular growth rate, baseline Epstein-Barr virus (EBV)
      copy number and ATP levels can all be confounders in such studies. Our objective
      is to better define confounding variables that affect pharmacological end points
      in LCLs. To this end, we evaluated the effect of these three variables on drug
      induced cytotoxicity in LCLs. The drugs evaluated included daunorubicin,
      etoposide, carboplatin, cisplatin, cytarabine, pemetrexed, 5'-deoxyfluorouridine,
      vorinostat, methotrexate, 6-mercaptopurine, and 5-fluorouracil. Baseline ATP or
      EBV copy number were not significantly correlated with cellular growth rate or
      drug-induced cytotoxicity. In contrast, cellular growth rate and drug-induced
      cytotoxicity were significantly, directly related for all drugs except
      vorinostat. Importantly, cellular growth rate is under appreciable genetic
      influence (h2=0.30-0.39) with five suggestive linkage regions across the genome.
      Not surprisingly, a percentage of SNPs that significantly associate with drug
      induced cytotoxicity also associate with cellular growth rate (P <= 0.0001).
      Studies using LCLs for pharmacologic outcomes should therefore consider that a
      portion of the genetic variation explaining drug-induced cytotoxicity is mediated
      via heritable effects on growth rate.

PMID- 20142841
TI  - Bipolar versus monopolar TURP: a prospective controlled study at two urology
      centers.
AB  - We compared bipolar and monopolar TURP in a prospective controlled study at two
      urology centers. The objective of the study was to establish whether there were
      differences between the two methods with regard to frequency of the transurethral
      resection (TUR) syndrome, amount of fluid absorbed during surgery, risk of
      hemorrhage, duration of postoperative catheterization and duration of
      hospitalization. The duration of surgery, improvement in maximum flow rate (Q
      max), residual urine volume, International Prostate Symptom Score (IPSS) and
      Quality of Life (QoL) score were also compared. Overall, our study showed that
      there were no major differences between bipolar and monopolar TURP. During follow
      up, the clinical efficacy of bipolar TURP has been maintained to the same degree
      as with the traditional method, with no significant differences for Q-max, IPSS
      and QoL scores after 1 year. Although the risk of developing TUR syndrome seemed
      to be smaller with bipolar resection (serum sodium change bipolar versus
      monopolar: +1.2 versus -0.1 mmol l(-1)), the bleeding tendency with both methods
      was the same (14.0 g l(-1) hemoglobin loss after 1 day in both groups). On the
      basis of our findings, we think that the monopolar technique has still a place in
      TURP.

PMID- 20142843
TI  - Targeted conditional gene knockout in human embryonic stem cells.

PMID- 20142842
TI  - BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin
      polymerization.
AB  - BCL2 is best known as a multifunctional anti-apoptotic protein. However, little
      is known about its role in cell-adhesive and motility events. Here, we show that
      BCL2 may play a role in the regulation of cell adhesion, spreading, and motility.
      When BCL2 was overexpressed in cultured murine and human cell lines, cell
      spreading, adhesion, and motility were impaired. Consistent with these results,
      the loss of Bcl2 resulted in higher motility observed in Bcl2-null mouse
      embryonic fibroblast (MEF) cells compared to wild type. The mechanism of BCL2
      regulation of cell adhesion and motility may involve formation of a complex
      containing BCL2, actin, and gelsolin, which appears to functionally decrease the
      severing activity of gelsolin. We have observed that the lysate from MCF-7 and
      NIH3T3 cells that overexpressed BCL2 enhanced actin polymerization in cell-free
      in vitro assays. Confocal immunofluorescent localization of BCL2 and F-actin
      during spreading consistently showed that increased expression of BCL2 resulted
      in increased F-actin polymerization. Thus, the formation of BCL2 and gelsolin
      complexes (which possibly contain other proteins) appears to play a critical role
      in the regulation of cell adhesion and migration. Given the established
      correlation of cell motility with cancer metastasis, this result may explain why
      the expression of BCL2 in some tumor cell types reduces the potential for
      metastasis and is associated with improved patient prognosis.

PMID- 20142844
TI  - AtFKBP53 is a histone chaperone required for repression of ribosomal RNA gene
      expression in Arabidopsis.
AB  - Chromatin structure is important for controlling gene expression, but mechanisms
      underlying chromatin remodeling are not fully understood. Here we report that an
      FKBP (FK506 binding protein) type immunophilin, AtFKBP53, possesses histone
      chaperone activity and is required for repressing ribosomal gene expression in
      Arabidopsis. The AtFKBP53 protein is a multidomain FKBP with a typical
      peptidylprolyl isomerase (PPIase) domain and several highly charged domains.
      Using nucleosome assembly assays, we showed that AtFKBP53 has histone chaperone
      activity and the charged acidic domains are sufficient for the activity. We show
      that AtFKBP53 interacts with histone H3 through the acidic domains, whereas the
      PPIase domain is dispensable for histone chaperone activity or histone binding.
      Ribosomal RNA gene (18S rDNA) is overexpressed when AtFKBP53 activity is reduced
      or eliminated in Arabidopsis plants. Chromatin immunoprecipitation assay showed
      that AtFKBP53 is associated with the 18S rDNA gene chromatin, implicating that
      AtFKBP53 represses rRNA genes at the chromatin level. This study identifies a new
      histone chaperone in plants that functions in chromatin remodeling and regulation
      of transcription.

PMID- 20142845
TI  - Ex vivo magnetic resonance imaging of crystalline lens dimensions in chicken.
AB  - PURPOSE: A reduction in the power of the crystalline lens during childhood is
      thought to be important in the emmetropization of the maturing eye. However, in
      humans and model organisms, little is known about the factors that determine the
      dimensions of the crystalline lens and in particular whether these different
      parameters (axial thickness, surface curvatures, equatorial diameter, and volume)
      are under a common source of control or regulated independently of other aspects
      of eye size and shape. METHODS: Using chickens from a broiler-layer experimental
      cross as a model system, three-dimensional magnetic resonance imaging (MRI) scans
      were obtained at 115-microm isotropic resolution for one eye of 501 individuals
      aged 3-weeks old. After fixation with paraformaldehyde, the excised eyes were
      scanned overnight (16 h) in groups of 16 arranged in a 2x2x4 array. Lens
      dimensions were calculated from each image by fitting a three-dimensional mesh
      model to the lens, using the semi-automated analysis program mri3dX. The lens
      dimensions were compared to measures of eye and body size obtained in vivo using
      techniques that included keratometry and A-scan ultrasonography. RESULTS: A
      striking finding was that axial lens thickness measured using ex vivo MRI was
      only weakly correlated with lens thickness measured in vivo by ultrasonography
      (r=0.19, p<0.001). In addition, the MRI lens thickness estimates had a lower mean
      value and much higher variance. Indeed, about one-third of crystalline lenses
      showed a kidney-shaped appearance instead of the typical biconvex shape. Since
      repeat MRI scans of the same eye showed a high degree of reproducibility for the
      scanning and mri3dX analysis steps (the correlation in repeat lens thickness
      measurements was r=0.95, p<0.001) and a recent report has shown that
      paraformaldehyde fixation induces a loss of water from the human crystalline
      lens, it is likely that the tissue fixation step caused a variable degree of
      shrinkage and a change in shape to the lenses examined here. Despite this serious
      source of imprecision, we found significant correlations between lens volume and
      eye/body size (p<0.001) and between lens equatorial diameter and eye/body size
      (p<0.001) in these chickens. CONCLUSIONS: Our results suggest that certain
      aspects of lens size (specifically, lens volume and equatorial diameter) are
      controlled by factors that also regulate the size of the eye and body
      (presumably, predominantly genetic factors). However, since it has been shown
      previously that axial lens thickness is regulated almost independently of eye and
      body size, these results suggest that different systems might operate to control
      lens volume/diameter and lens thickness in normal chickens.

PMID- 20142846
TI  - A splice site mutation in CRYBA1/A3 causing autosomal dominant posterior polar
      cataract in a Chinese pedigree.
AB  - PURPOSE: To identify the mutant gene for autosomal dominant posterior polar
      congenital cataract in a four-generation Chinese pedigree. METHODS: The clinical
      data of patients from the family were recorded by slit-lamp photography. Genomic
      DNA samples from peripheral blood of the pedigree members were then isolated to
      map the relevant gene, using microsatellite markers for two-point linkage
      analysis. Genotype and haplotypes of the pedigree were constructed using Cyrillic
      software to locate the relevant region. Direct sequencing was performed to screen
      out the disease-causing mutation. RESULTS: The congenital cataract phenotype of
      the pedigree was labeled as the posterior polar type by using slit-lamp
      photography. Linkage analysis results indicated a maximum logarithm of odds LOD
      score of (Z(max)) 2.02 at D17S1800 (theta(max)=0.00). Haplotyping identified a 26
      cM region flanked by D17S921 and D17S800 on 17p12-21.2, namely at the betaA1/A3
      crystallin (CRYBA1/A3) gene locus. Sequencing revealed a splice site mutation, G-
      >A, at the first base of intron 3 of CRYBA1/A3, which co-segregated with the
      affected individuals in the pedigree but which was not found in the unaffected
      members of the family or in the 50 unrelated controls. CONCLUSIONS: Our results
      demonstrated that a splice site mutation of CRYBA1/A3 was responsible for the
      autosomal dominant posterior polar congenital cataract in a four-generation
      Chinese pedigree. The same mutation in this gene had previously been reported to
      be associated with other phenotype cataracts. This study is the first report
      relating a mutation of CRYBA1/A3 to posterior polar cataract.

PMID- 20142847
TI  - Differential expression of transforming growth factor-beta isoforms in bullous
      keratopathy corneas.
AB  - PURPOSE: The aim of this study was to investigate transcriptional activities of
      genes encoding transforming growth factor (TGF)-beta isoforms in bullous
      keratopathy corneas. METHODS: The study group consisted of 45 patients with
      bullous keratopathy (22 females and 23 males). The control group included 45
      corneal donors (21 females and 24 males). Quantification of TGF-beta1, TGF-beta2,
      and TGF-beta3 mRNAs was performed by real-time quantitative reverse transcription
      PCR (QRT-PCR). RESULTS: TGF-beta1, TGF-beta2, and TGF-beta3 mRNAs were detected
      in both normal and pseudophakic bullous keratopathy (PBK) corneas. We found
      significantly lower transcriptional activity of TGF-beta3 mRNA in bullous
      keratopathy corneas compared to normal tissues. TGF-beta1 and TGF-beta2
      expressions were at the same level in both PBK and healthy corneas. CONCLUSIONS:
      Downregulation of TGF-beta3 gene expression may play a significant role in
      molecular changes observed in bullous keratopathy.

PMID- 20142848
TI  - Ethnicity-based subgroup meta-analysis of the association of LOXL1 polymorphisms
      with glaucoma.
AB  - PURPOSE: To investigate the association and ethnic heterogeneity of lysyl oxidase
      like 1 (LOXL1) single nucleotide polymorphisms (SNPs) with exfoliation syndrome
      (XFS)/exfoliation glaucoma (XFG) and other types of glaucoma. METHODS: We
      performed meta-analysis and ethnicity-based subgroup analyses according to
      published studies. Allele and genotype frequencies of SNPs rs1048661, rs2165241,
      and rs3825942 were extracted for analysis in Reviewer Manager: (1) comparison of
      the allelic distributions between XFS and XFG, (2) allelic association of LOXL1
      SNPs with XFS/XFG, (3) associations in homozygote, heterozygote, and dominant and
      recessive models, and (4) allelic association with primary open angle glaucoma
      (POAG). RESULTS: In total 24 reported articles were retrieved, including
      Caucasian, African, Japanese, Indian, and Chinese populations. There was no
      significant difference in the distributions of rs1048661, rs2165241, and
      rs3825942 between XFS and XFG. The G allele of rs3825942 was the common at-risk
      allele for XFS/XFG in all populations with a total odds ratio (OR) of 10.89. The
      total homozygote OR of rs3825942 was 9.06 for XFS/XFG combined, but the total
      heterozygote OR was not significant. We also found that in the recessive model,
      the total OR was 14.70. There was no association of the three SNPs with POAG.
      CONCLUSIONS: The association of rs3825942, but not rs2165241 or rs1048661, with
      XFS/XFG is consistent in different ethnic populations in the recessive model.
      LOXL1 is not associated with POAG in all study populations.

PMID- 20142851
TI  - The National Health Bill 2009 and afterwards.

PMID- 20142850
TI  - New mutations in BBS genes in small consanguineous families with Bardet-Biedl
      syndrome: detection of candidate regions by homozygosity mapping.
AB  - PURPOSE: Bardet-Biedl syndrome (BBS, OMIM 209900) is a rare multi-organ disorder
      in which BBS patients manifest a variable phenotype that includes retinal
      dystrophy, polydactyly, mental delay, obesity, and also reproductive tract and
      renal abnormalities. Mutations in 14 genes (BBS1-BBS14) are found in 70% of the
      patients, indicating that additional mutations in known and new BBS genes remain
      to be identified. Therefore, the molecular diagnosis of this complex disorder is
      a challenging task. METHODS: In this study we show the use of the genome-wide
      homozygosity mapping strategy in the mutation detection of nine Caucasian BBS
      families, eight of them consanguineous and one from the same geographic area with
      no proven consanguinity. RESULTS: We identified the disease-causing mutation in
      six of the families studied, five of which had novel sequence variants in BBS3,
      BBS6, and BBS12. This is the first null mutation reported in BBS3. Furthermore,
      this approach defined homozygous candidate regions that could harbor potential
      candidate genes for BBS in three of the families. CONCLUSIONS: These findings
      further underline the importance of homozygosity mapping as a useful technology
      for diagnosis in small consanguineous families with a complex disease like BBS.

PMID- 20142849
TI  - Proliferative diabetic retinopathy and relations among antioxidant activity,
      oxidative stress, and VEGF in the vitreous body.
AB  - PURPOSE: To investigate the relationships among antioxidant activities, oxidative
      stress, and vascular endothelial growth factor (VEGF) in the vitreous body and
      serum from proliferative diabetic retinopathy (PDR) patients. METHODS: In 21
      patients with PDR and 21 controls with macular hole (MH), the VEGF and lipid
      peroxide (Nepsilon-hexanoyl-lysine [HEL]) levels in the vitreous and serum were
      measured by enzyme-linked immunosorbent assay, while antioxidant capacity
      (potential antioxidant [PAO]) was measured by chemical reduction of Cu(2+).
      RESULTS: Both the PAO and HEL levels in the vitreous and serum were significantly
      higher in PDR patients than in those with MH (both p<0.01). The VEGF
      concentrations in the vitreous were higher in PDR patients than in those with MH
      (p<0.01); however, the VEGF concentrations in the serum were not different
      between the two groups (p=0.95). Positive correlations were found between the PAO
      and VEGF concentrations and between the HEL and VEGF concentrations in the
      vitreous of both the PDR and the MH patients. CONCLUSIONS: Our study revealed
      that the PAO, HEL, and VEGF concentrations in the vitreous were increased in PDR
      versus MH patients and that there were positive correlations among these factors.
      This is consistent with VEGF and lipid peroxide levels in the vitreous playing
      some role in the pathogenesis of PDR.

PMID- 20142852
TI  - Classification and diagnosis of the inherited neuropathies.

PMID- 20142854
TI  - Taare Zameen Par and dyslexic savants.
AB  - The film Taare Zameen Par (Stars upon the Ground) portrays the tormented life at
      school and at home of a child with dyslexia and his eventual success after his
      artistic talents are discovered by his art teacher at the boarding school. The
      film hints at a curious neurocognitive phenomenon of creativity in the midst of
      language disability, as exemplified in the lives of people like Leonardo da Vinci
      and Albert Einstein, both of whom demonstrated extraordinary creativity even
      though they were probably affected with developmental learning disorders. It has
      been hypothesized that a developmental delay in the dominant hemisphere most
      likely 'disinhibits' the nondominant parietal lobe, unmasking talents-artistic or
      otherwise-in some such individuals. It has been suggested that, in remedial
      training, children with learning disorders be encouraged to develop such hidden
      talents to full capacity, rather than be subjected to the usual overemphasis on
      the correction of the disturbed coded symbol operations.

PMID- 20142853
TI  - Role of multidrug transporters in neurotherapeutics.
AB  - Acquired resistance to antibiotics and other chemotherapeutic agents is a major
      problem in the practice of neurology and other branches of medicine. There are
      several mechanisms by which drug resistance is acquired. Multidrug transporters
      are important glycoproteins located in the cell membrane that actively transport
      small lipophilic molecules from one side of the cell membrane to the other, most
      often from the inside to the outside of a cell. They have important protective
      role yet may prove inconvenient in chemotherapy. In epilepsy and other disorders
      this mechanism augments the elimination of drugs from their target cells and
      leads to drug resistance. In this review, we have discussed the biochemical
      characteristics of multidrug transporters and the mechanisms by which these
      membrane bound proteins transport their target molecules from one side to the
      other side of the cell membrane. We have also briefly discussed the application
      of this knowledge in the understanding of drug resistance in various clinical
      situations with particular reference to neurological disorders. These proteins
      located in the placenta have important role in preventing the transplacental
      movement of drugs in to the fetus which may result in congenital malformations or
      other defects. The molecular genetic mechanisms that govern the expression of
      these important proteins are discussed briefly. The potential scope to develop
      targeted chemotherapeutic agents is also discussed.

PMID- 20142855
TI  - Urodynamics post stroke in patients with urinary incontinence: Is there
      correlation between bladder type and site of lesion?
AB  - OBJECTIVE: Assessment of bladder by urodynamic study (UDS) in patients with
      urinary incontinence following stroke, and correlation with site of lesion. STUDY
      DESIGN AND SETTING: Retrospective cross-sectional study in the neurological
      rehabilitation unit of a tertiary care institute. MATERIALS AND METHODS: Forty
      patients (22 males) with arterial or venous, ischemic or hemorrhagic stroke, with
      urinary incontinence in the acute phase following the event, underwent UDS.
      Seventeen patients had right hemiplegia, 18 had left hemiplegia, and five had
      posterior circulation stroke with brainstem/cerebellar features. Bladder type was
      correlated with age, side, and site of lesion. RESULTS: The mean age was 46.80 +/
      16.65 years (range: 18-80 years). Thirty-six patients had arterial stroke and
      four had cortical venous thrombosis. UDS was performed after a mean of 28.32 +/-
      10.27 days (range: 8-53 days) after the stroke. All but one patient had
      neurogenic bladder dysfunction, with 36 patients (90%) having overactive detrusor
      (OD) and three having underactive/areflexic detrusor. Among the 36 patients with
      OD, 25 patients (62.5%) had OD without detrusor-sphincter dyssynergy (DSD) and 11
      (27.5%) had OD with DSD. Bladder management was advised based on the UDS
      findings. No significant correlation (P > 0.05) was found between type of bladder
      and age or side and site of lesion. CONCLUSIONS: UDS is a useful tool to assess
      and manage the bladder following stroke with urinary incontinence. In this study,
      no significant correlation was found between UDS findings and site of lesion.

PMID- 20142856
TI  - Comparison of psychosocial factors between patients with benign fasciculations
      and those with amyotrophic lateral sclerosis.
AB  - In this retrospective study, we compared the initial presentation of patients who
      were eventually diagnosed with either benign fasciculations (BF) or amyotrophic
      lateral sclerosis (ALS). We found a significantly higher number of patients with
      BF reporting a past history of psychiatric symptoms, life stressors, and
      concurrent psychosomatic symptoms. There was no difference between the two groups
      in patient report of current anxiety or depression symptoms. These findings
      support our hypothesis that BF are a manifestation of psychological distress due
      to somatization and that reviewing psychosocial history is important when
      patients are being evaluated for fasciculations. Patients seeking medical
      attention for fasciculations and who do not report a history of underlying
      psychiatric or psychosomatic disorders should be followed closely as
      fasciculations have been reported to be a presenting feature of ALS.

PMID- 20142857
TI  - Radial neuropathy due to occupational lead exposure: Phenotypic and
      electrophysiological characteristics of five patients.
AB  - Lead is a ubiquitous and versatile metal that has been used by mankind for many
      years. It is a toxic heavy metal that ranks as one of the most important
      environmental poisons in the world. Research conducted in recent years has
      increased public health concern about the toxicity of lead at low doses and has
      supported a reappraisal of the levels of lead exposure that may be safely
      tolerated in the workplace. Neuropathy is one complication of lead poisoning. The
      aim of this study is to describe the phenotypic and electrophysiological profile
      in five male patients working in a battery factory who developed radial nerve
      neuropathy due to lead exposure. All patients had elevated blood lead levels that
      were in the toxic range. The concerned regulatory bodies should make it mandatory
      for workers to undergo regular health checkups to detect signs of lead poisoning
      and must ensure that workers are aware about the ill effects of exposure to this
      metal. Chelation therapy removes lead from the blood and soft tissues and chronic
      lead exposure often requires repeated courses of treatment.

PMID- 20142858
TI  - Clinical, electrophysiological, and prognostic study of postinjection sciatic
      nerve injury: An avoidable cause of loss of limb in the peripheral medical
      service.
AB  - BACKGROUND: Post injection sciatic nerve injury is a common cause of sciatic
      nerve mononeuropathy in the developing world largely due to inadequate health
      care facilites in the rural regions. OBJECTIVE: The study was conducted to
      analyse the pattern of this nerve lesion in clinical and electrophysiological
      parameters and also to study the outcome in a conservatively treated cohort.
      MATERIALS AND METHODS: One hundred and six patients who underwent evaluation at
      our laboratory from 2000 to 2006 for post injection sciatic neuropathy formed the
      study population. Twenty two of these were followed up (mean 6.6 months) for the
      outcome. RESULTS: In the cases with full data, common peroneal division of the
      sciatic nerve was affected alone or predominantly. On follow up, 72% cases showed
      little or partial recovery. Thirty two percent patients had residual trophic
      changes and causalgia at their last visit. CONCLUSION: The majority of cases of
      postinjection sciatic nerve injury have poor prognosis on conservative treatment.

PMID- 20142859
TI  - Apraxic agraphia: An insight into the writing disturbances of posterior aphasias.
AB  - BACKGROUND: Reading and writing disturbances are common accompaniments of aphasia
      following brain damage. However, impaired writing in the absence of apparent
      primary linguistic disturbances is infrequently reported in the literature.
      MATERIALS AND METHODS: A 67-year-old right-handed subject underwent neurological,
      neuroradiological, and linguistic investigations following development of a
      minimal right upper limb weakness. RESULT: The patient had polycythemia and the
      neurological investigation revealed right upper limb paresis. The
      neuroradiological investigation revealed hypodense areas involving the gray-white
      matter of the left postero-parietal and frontal lobe, left caudate and lentiform
      nuclei, and the anterior limb of the internal capsule, suggesting an infarct. The
      linguistic investigation revealed a mild anomic aphasia with apraxic agraphia.
      This mild anomic aphasia resulted primarily from the relatively poor scores on
      the verbal fluency tests. DISCUSSION: The marked writing impairment, even with
      the left hand, points to disturbances in written output - apraxic agraphia - in
      the presence of near-normal spoken output. This finding should raise suspicion
      about hidden apraxic agraphia in subjects with posterior aphasias.

PMID- 20142860
TI  - Primary Sjogren's syndrome manifesting as multiple cranial neuropathies: MRI
      findings.
AB  - We report a case of primary Sjogren's syndrome presenting with multiple cranial
      nerve palsies and radiological evidence of cranial pachymeningitis and
      hypophysitis. A 47-year-old woman developed right sensory neural hearing loss
      followed, 2 months later, by right facial palsy. Cranial magnetic resonance
      imaging showed features of pachymeningitis and pituitary gland infiltration. The
      diagnosis of primary Sjogren's syndrome was confirmed by demonstrating positive
      SS-A and SS-B antibodies and histological evidence of lymphocytic infiltration of
      the sublabial salivary gland. During the 2-year follow-up, the patient had
      transient VI(th), IX(th), X(th), and XII(th) cranial nerve palsies. Sjogren's
      syndrome should be considered in the differential diagnosis of patients
      presenting with multiple recurrent cranial nerve palsies, even if prominent sicca
      symptoms are absent.

PMID- 20142861
TI  - Flail arm-like syndrome associated with HIV-1 infection.
AB  - During the last 20 years at least 23 cases of motor neuron disease have been
      reported in HIV-1 seropositive patients. In this report we describe the clinical
      picture of a young man with HIV-1 clade C infection and flail arm-like syndrome,
      who we were able to follow-up for a long period. We investigated and
      prospectively monitored a 34-year-old man with features of flail arm syndrome,
      who developed the weakness and wasting 1 year after being diagnosed with HIV-1
      infection after a routine blood test. He presented in 2003 with progressive,
      symmetrical wasting and weakness of the proximal muscles of the upper limb of 2
      years' duration. He had severe wasting and weakness of the shoulder and arm
      muscles. There were no pyramidal signs. He has been on HAART for the last 4 years
      and the weakness or wasting has not worsened. At the last follow-up in July 2007,
      the patient had the same neurological deficit and no other symptoms or signs of
      HIV-1 infection. MRI of the spinal cord in 2007 showed characteristic T2
      hyperintense signals in the central part of the spinal cord, corresponding to the
      central gray matter. Thus, our patient had HIV-1 clade C infection associated
      with a 'flail arm-like syndrome.' The causal relationship between HIV-1 infection
      and amyotrophic lateral sclerosis (ALS)-like syndrome is still uncertain. The
      syndrome usually manifests as a lower motor neuron syndrome, as was seen in our
      young patient. It is known that treatment with antiretroviral therapy (ART)
      stabilizes/improves the condition. In our patient the weakness and atrophy
      remained stable over a period of 3.5 years after commencing HAART regimen.

PMID- 20142862
TI  - No footprints, yet after the leader.

PMID- 20142863
TI  - Madelung's disease with myopathy.

PMID- 20142864
TI  - 'Hummingbird' sign in progressive supranuclear palsy.

PMID- 20142865
TI  - Similar calcifications of the brain on computed tomography, but different
      etiologies.

PMID- 20142866
TI  - My fellow.

PMID- 20142867
TI  - Type 1 diabetes research: Newer approaches and exciting developments.

PMID- 20142868
TI  - Prevalence of the metabolic syndrome in acute myocardial infarction and its
      impact on hospital outcomes.
AB  - AIMS: To ascertain the prevalence of the metabolic syndrome in patients with
      acute myocardial infarction; to study the impact of the metabolic syndrome on
      hospital outcomes; and to find out the association of each component of the
      metabolic syndrome with acute myocardial infarction (AMI). SETTING: Coronary care
      unit, Department of Medicine, B P Koirala Institute of Health Sciences, Dharan,
      Nepal. DESIGN: Hospital-based cross-sectional study. MATERIALS AND METHODS: A
      total of 84 unselected consecutive patients hospitalized with AMI (diagnosed on
      the basis of WHO criteria) were categorized according to NCEP ATP III criteria.
      STATISTICAL ANALYSIS: Data was analyzed by using the Student's t test and Chi
      square test. RESULTS: Among the 84 AMI patients, 22 (26.19%) fulfilled the
      criteria for metabolic syndrome. Patients with the metabolic syndrome were older
      (86% were >50 years of age) and females (27%) were more affected than males
      (25%). In-hospital case fatality was higher in patients having the metabolic
      syndrome (5/22) than in those without the syndrome (3/62). Among the five
      components of the metabolic syndrome, the triglyceride levels had the highest
      positive predictive value (62%) in AMI; this was followed by fasting blood
      glucose levels (55%). CONCLUSION: The prevalence of the metabolic syndrome is
      26.19%; it is associated with high mortality; among its components, the
      triglyceride level has the highest positive predictive value in AMI patients.

PMID- 20142869
TI  - Evaluation of the efficacy of pulsed electromagnetic field in the management of
      patients with diabetic polyneuropathy.
AB  - AIM: The study was carried out to evaluate and compare the effect of low power,
      low frequency pulsed electromagnetic field (PEMF) of 600 and 800 Hz,
      respectively, in management of patients with diabetic polyneuropathy. SETTINGS
      AND DESIGNS: The study was a randomized controlled trial performed in Guru Nanak
      Dev University and Medical College, Amritsar, India with different subject
      experimental design. MATERIALS AND METHODS: Thirty subjects within an age group
      of 40-68 years with diabetic polyneuropathy stages N1a, N1b, N2a were randomly
      allocated to groups 1, 2, 3 with 10 subjects in each. Group 1 and 2 were treated
      with low power 600 and 800-Hz PEMF for 30 min for 12 consecutive days. Group 3
      served as control on usual medical treatment of diabetic polyneuropathy (DPN).
      The subjects with neuropathy due to any cause other than diabetes were excluded.
      The pain and motor nerve conduction parameters (distal latency, amplitude, nerve
      conduction velocity) were assessed before and after treatment. STATISTICAL
      ANALYSIS: Related t-test and unrelated t-test were used for data analysis.
      RESULTS: Significant reduction in pain and statistically significant (P<0.05)
      improvement in distal latency and nerve conduction velocity were seen in
      experimental group 1 and 2. CONCLUSIONS: Low-frequency PEMF can be used as an
      adjunct in reducing neuropathic pain as well as for retarding the progression of
      neuropathy in a short span of time.

PMID- 20142870
TI  - Effect of Ramadan fasting on anthropometric parameters and food consumption in
      276 type 2 diabetic obese women.
AB  - AIM: To assess the effect of Ramadan fasting on body weight and food consumption
      in type 2 diabetic obese women. MATERIALS AND METHODS: A total of 276 outpatient
      women receiving oral antidiabetic drugs (OADs) (BMI = 34.63 +/- 3.29 kg/m(2)),
      aged 49 (+/-6 years), were selected. The study was carried out over three periods
      - before (T1: prefasting), during (T2: fasting), and after (T3: postfasting)
      Ramadan - in three towns located in the northwestern region of Algeria. During
      the course of 3 days, the daily food intake and anthropometric parameters weight,
      height, waist and hip circumferences, body mass index (BMI), and waist-hip ratio
      (WHR) were recorded. A one-way repeated measures ANOVA test was used to compare
      the groups. RESULTS: The main effect of fasting during Ramadan was a significant
      weight loss (-3.12 kg i.e. 3.70%; P < 0.01), a decrease in meal frequency (2.2 +/
      0.3 vs. 4.3 +/- 0.4) as well as in energy intake (1488 +/- 118 vs.1823 +/- 262
      Kcal/d) and an important increase in dietary fat consumption (35.84 vs. 25.36%),
      especially the saturated one (231Kca/d i.e. 43.25%) of total fat, dietary
      cholesterol (392 +/- 121 vs. 221 +/- 73 mg/d), and polyunsaturated fatty acids
      (PUFA). Except in three cases, there were no frequent hypoglycaemic episodes
      observed among the participants. CONCLUSIONS: Fasting during the month of Ramadan
      causes weight loss and decrease in calorie intake, which is correlated with a
      decrease in meal frequency. However, more foods rich in fat and dietary
      cholesterol were consumed during this period. The latter could constitute a high
      risk for diabetics who are fasting, in particular when medication advice and/or
      health care control are insufficient or ignored.

PMID- 20142871
TI  - Survey of childhood diabetes and impact of school level educational interventions
      in rural schools in Karimnagar district.
AB  - CONTEXT: Diabetes in children is increasing to epidemic proportions. It is
      essential to prevent its occurrence by screening for its modifiable risk factors
      at an earliest time. AIMS: 1. To screen for childhood diabetes and its modifiable
      risk factors like obesity, physical inactivity, excessive eating of sweets,
      carbohydrate foods and chocolate intake and prolonged TV viewing. 2. To bring
      about reduction in these risk factors by lifestyle modifications through school
      health teams. SETTINGS AND DESIGN: A combined cross-sectional descriptive and
      interventional design among urban and rural school children was conducted.
      MATERIALS AND METHODS: Survey was conducted among 610 school children by 8
      resident doctors to know the modifiable risk factors for diabetes. Four
      educational interventions to reduce and prevent the risk factors were carried out
      by the school health teams. STATISTICAL ANALYSIS USED: Proportions; chi(2) test,
      t-test, cluster sampling. RESULTS: About 3.5% of children were diabetic.
      Reductions by 0.33%, 27.5%, 17%, 19% were achieved respectively in obesity,
      sweets/ chocolates/ carbohydrate rich food consumption, sedentary life and
      prolonged TV viewing. CONCLUSIONS: Childhood diabetes burden can be minimized by
      preventing the development of risk factors like obesity, sedentary life and
      eating excess of sweets, carbohydrate rich foods and chocolates. School level
      educational interventions through teacher-parent-child teams will definitely
      reduce the prevalence of diabetes.

PMID- 20142872
TI  - A comparative evaluation of safety and efficacy of rosuvastatin, simvastatin, and
      atorvastatin in patients of type 2 diabetes mellitus with dyslipidemia.
AB  - AIM: To evaluate and compare the safety and efficacy of rosuvastatin,
      simvastatin, and atorvastatin in patients of type 2 diabetes mellitus with
      dyslipidemia. MATERIALS AND METHODS: This open-label, randomized, parallel group,
      comparative, prospective study of 12-weeks duration included 60 patients of type
      2 diabetes with dyslipidemia having good glycemic control with fixed dose
      combination of tablet glimepiride + metformin and divided into three groups of
      twenty each. Group-1 patients have received tablet rosuvastatin 10 mg once daily,
      group-2 received tablet atorvastatin 10 mg once daily, and group-3 received
      tablet simvastatin 10 mg once daily for 12 weeks each. The levels of serum
      cholesterol, serum triglyceride, LDL, VLDL, and HDL were assessed at baseline and
      at the end of 12 weeks. RESULTS: The mean serum cholesterol, serum triglyceride,
      LDLc, and VLDLc levels were significantly reduced on therapy (P<0.001).
      Simultaneously, the mean levels of HDL were highly significantly increased
      (P<0.001) after therapy for 12 weeks with rosuvastatin, atorvastatin, and
      simvastatin. Reduction of LDL levels in rosuvastatin group was statistically
      significant when compared with those of simvastatin group (P< 0.05) but was
      statistically nonsignificant when compared with atorvastatin group (P> 0.05).
      CONCLUSION: 10 mg of rosuvastatin was comparable to 10 mg of atorvastatin and
      more efficacious than 10 mg simvastatin in reducing LDL levels after 12 weeks of
      therapy in patients of type 2 diabetes mellitus with dyslipidemia.

PMID- 20142873
TI  - Lipoprotein (a) in type 2 diabetes mellitus: Relation to LDL:HDL ratio and
      glycemic control.
AB  - BACKGROUND: Increased lipoprotein (a) [Lp (a)] concentrations are predictive of
      coronary artery disease (CAD). Type 2 diabetes mellitus also leads to
      dyslipidemia, like elevated triglyceride levels and low HDL levels, which are
      known risk factors for CAD. This study was designed to investigate the levels of
      Lp (a) in type 2 diabetic patients and their association with LDL: HDL ratio and
      glycemic control. MATERIALS AND METHODS: The study included 60 patients of type 2
      diabetes and 50 age and sex matched controls. The Lp(a) levels in the diabetic
      group were compared with the control group and the relationship between the Lp(a)
      levels and LDL: HDL ratio was evaluated. Diabetic group was further divided into
      three subgroups according to levels of glycated hemoglobin. Lp(a) levels and
      glycated hemoglobin in controlled and uncontrolled diabetes mellitus were also
      compared to find out any correlation between them. Statistical analysis was done
      using the students 't' test and Chi square test. RESULTS: Lp(a) levels were found
      to be significantly increased in the diabetic group as compared to the control
      group (P< 0.001). LDL: HDL ratio was also increased in the diabetic group as
      compared to the control group. Lp(a) levels showed no association with LDL: HDL
      ratio and degree of glycemic control in these patients. CONCLUSIONS: The results
      of the present study suggest that Lp(a) levels are increased in type 2 diabetic
      patients. The elevated Lp(a) levels do not reflect the glycemic status and are
      also independent of increase in LDL:HDL ratio suggesting different metabolic
      pathways and the genetic connection for LDL and Lp(a).

PMID- 20142875
TI  - Bridging the gap...From clinical research to clinical practice.

PMID- 20142876
TI  - We have a dream...In pursuit of excellence.

PMID- 20142874
TI  - Approaches in type 1 diabetes research: A status report.
AB  - Type 1 diabetes is a multifactorial disease with an early age of onset, in which
      the insulin producing beta cell of the pancreas are destroyed because of
      autoimmunity. It is the second most common chronic disease in children and
      account for 5% to 10% of all diagnosed cases of diabetes. India is having an
      incidence of 10.6 cases/year/100,000, and recent studies indicate that the
      prevalence of type 1 diabetes in India is increasing. However in view of poor
      health care network, there is no monitoring system in the country. Of the 18
      genomic intervals implicated for the risk to develop type 1 diabetes, the major
      histocompatibility complex (MHC) region on chromosome 6p21.31 has been the major
      contributor estimated to account for 40-50%, followed by 10% frequency of INS
      VNTR at 5' flanking region of the insulin gene on chromosome 11p15.5. However,
      population studies suggest that > 95% of type 1 diabetes have HLA-DR3 or DR4, or
      both, and in family studies, sibling pairs affected with type 1 diabetes have a
      non-random distribution of shared HLA haplotypes. As predisposing genetic factors
      such as HLA alleles are known, immunological interventions to prevent type 1
      diabetes are of great interest. In the present study we have reviewed the status
      of molecular genetics of the disease and the approaches that need to be adopted
      in terms of developing patient and suitable control cohorts in the country.

PMID- 20142877
TI  - A new paradigm for operative dentistry.
AB  - It is over 100 years since G V black gathered together most of the knowledge then
      current on the caries process and set clear parameters for the discipline of
      operative dentistry. His four-volume treatise set standards that were relevant
      for the times and, in fact, were so well described that they remained dominant in
      this discipline until quite recently. However, over the last 50 years there has
      been great progress in scientific method and in knowledge of the common diseases
      of the oral environment, including the caries process, so maybe it is time for
      change. The term "paradigm" describes a philosophy of science, a generally
      accepted model of how ideas relate to one another, forming a conceptual framework
      within which scientific research is carried out. Black defined the paradigm
      within which further research was to be conducted during the following years and
      the profession accepted his lead. However, it is not expected that the parameters
      of a profession should remain unchanged over a substantial period so it is
      suggested that the dental profession should, at this time, recognize a new
      paradigm. Improvements in scientific method have led to a better understanding of
      the oral environment, resulting in extensive changes for this profession. It is
      suggested that the standards set by Black should be now consigned to history and
      an entirely new paradigm adopted. First, the profession must recognize that
      dental caries is a bacterial disease and its primary efforts should be directed
      towards identification and elimination of the disease prior to initiating repair
      of the damage that it has caused. Preservation of natural tooth structure is then
      the next responsibility. There should be maximum use made of preventive
      strategies, including remineralization, followed by minimal intervention cavity
      designs and the use of bioactive restorative materials to restore the lesions.
      The profession should be prepared to move on.

PMID- 20142878
TI  - Dentine deproteinization and microleakage around gingival third resin
      restorations.
AB  - OBJECTIVES: A significant factor in achieving satisfactory adhesion of
      restorative resins to dentine substrate is the method by which the dentine
      surface is treated before an adhesive is applied. The aim of this study was to
      evaluate the effect of deproteinization on microleakage around gingival third
      resin restorations. MATERIALS AND METHODS: Standardised Class V preparations were
      made on randomly selected intact upper and lower human molars. These were treated
      in one of five ways (no treatment, enamel etch only, total etch, total etch
      followed by deproteinization, and deproteinization only) and then adhesively
      bonded using either an acetone or ethanol based bonding system. The samples were
      first immersed in 2% methylene blue dye and then 35% nitric acid, for 72 hours
      each. The solutions were filtered and centrifuged, and the supernatant was used
      to determine absorbance in a spectrophotometer at 670 nm. The results were
      recorded as a measure of transmission of light of the test solutions. RESULTS:
      The results were subjected to multiple comparisons amongst groups, using anova.
      There was a statistically significant difference between all treatment groups for
      the two different bonding systems used. The experimental groups, total etch alone
      and total etch followed by deproteinization showed statistically significant
      differences, as compared to all other groups. However, although the total etch
      group showed a decrease in microleakage, when compared to the total etch followed
      by deproteinization group, this was not statistically significant. CONCLUSION:
      Within the limitations of this study, collagen removal may be important to reduce
      microleakage whilst using acetone based adhesive systems and it may not influence
      the amount of microleakage for ethanol or water based adhesive systems.

PMID- 20142879
TI  - Evaluation of natural smile: Golden proportion, RED or Golden percentage.
AB  - Creating geometric or mathematical proportion to relate the successive width of
      maxillary anterior teeth is a critical aspect in Esthetic dentistry. Golden
      proportion, recurring esthetic dental (RED) proportion and golden percentage are
      new theories in this field. AIM: To investigate the existence and suitability of
      Golden proportion, Recurring Esthetic Dental, and Golden percentage between the
      widths of maxillary anterior teeth in individuals with natural dentition, with
      the aid of digital photographs and computer analysis. MATERIAL AND METHODS:
      Standardized frontal images of 56 dental students, 20 male and 36 female, were
      captured. Each maxillary anterior tooth was digitally measured. Once the
      measurements were recorded, the three theories were applied and the data was
      analyzed statistically. RESULTS: The golden proportion was found to exist only in
      14-25% of the subjects, between perceived maxillary anterior teeth in natural
      dentition. The value of RED proportion was not constant, and as one moved
      distally, this proportion gradually increased. Furthermore, the results revealed
      that golden percentage was rather constant in terms of relative tooth width.
      Central incisor represented 22%, lateral incisor 15% and canine 13% of the width
      of six maxillary anterior teeth, as viewed from the front. CONCLUSION: Both
      golden proportion and RED proportion are unsuitable methods to relate the
      successive width of the maxillary anterior teeth in natural dentition. However,
      the golden percentage theory can be applied if percentages are adjusted, taking
      into consideration the ethnicity of the population.

PMID- 20142880
TI  - Comparative evaluation of maintenance of cell viability of an experimental
      transport media "coconut water" with Hank's balanced salt solution and milk, for
      transportation of an avulsed tooth: An in vitro cell culture study.
AB  - The purpose of this study was to evaluate the efficiency of a new storage medium,
      coconut water, in comparison with other traditional storage media like Hank's
      balanced salt solution (HBBS) and milk, in maintaining the viability of an
      established cell line BHK-21/C13 (baby hamster kidney fibroblasts) using the
      direct suspension cell culture technique.The storage media tested in the study
      were divided into three major groups and two control groups - Group A: HBBS,
      Group B: milk, and Group C: coconut water. The positive and negative controls
      corresponded to 0-minute and 24-hour dry times respectively.The three groups were
      then divided into five subgroups, each denoting the storage time periods 15 min,
      30 min, 45 min, 60 min and 120 min respectively. The cell line BHK-21/C13 was
      subcultured and the number of cells was standardized by making a cell suspension
      using Minimal Essential Medium in five culture plates.One ml of each experimental
      group (HBBS, milk and coconut water) was added to eight wells of each culture
      plate. The culture plates containing the cells and the experimental groups were
      incubated for the respective time periods. The cells were then counted with a
      Neubauer counting chamber, under light microscope. The results were statistically
      analyzed using One-way ANOVA and Multiple Range Test using the Tukey-HSD
      procedure to identify the significant groups at p </= 0.05.Within the parameters
      of this study, it appears that coconut water may be a better alternative to HBSS
      or milk, in terms of maintaining cell viability. Coconut water can be used as a
      superior transport medium for avulsed teeth.

PMID- 20142881
TI  - Shear bond strength of eugenol- and non-eugenol-based endodontic sealers to gutta
      percha and dentin: An in vitro study.
AB  - AIMS: a) To evaluate the bond strength of eugenol- and non-eugenol-based
      endodontic sealers to gutta-percha and dentin and b) To make a comparative
      evaluation of the bond strength of sealers to gutta-percha and dentin. MATERIAL
      AND METHODS: Seventy-two specimens were used in this study, which was divided
      into two groups - group I consisting of 36 freshly extracted human molars with 2
      mm coronal cut surface; and group II consisting of gutta-percha disks of 10 mm
      diameter and 2 mm thickness embedded in 36 plaster of Paris specimens. Group I
      was further divided into three subgroups: subgroup 1, subgroup 2, and subgroup 3,
      consisting of 12 teeth each; and group II was further divided into three
      subgroups: subgroup 1, subgroup 2, and subgroup 3, consisting of 12 plaster
      specimens each. Each subgroup consisted of two materials each, which were placed
      in 5 mm long sections of polyethylene tubing and were then placed on coronal 2 mm
      cut surface of human molars; likewise subgroup 1, subgroup 2, and subgroup 3 of
      group II consisted of two materials each, which were also placed in 5 mm long
      sections of polyethylene tubing and then placed on gutta-percha disks 10 mm in
      diameter and 2 mm in thickness, which were embedded in the plaster specimens.
      After the materials were set, the specimens were subjected to test for shearing
      bond strength using a universal testing machine (Instron). STATISTICAL ANALYSIS:
      Mann-Whitney U test. RESULTS: Group I, i.e., zinc oxide eugenol sealers, showed
      more bond to gutta-percha than to dentin, in which subgroup 2b, endomethasone,
      showed the maximum bond. Group II, i.e., non-zinc oxide eugenol sealers, showed
      more bond to dentin than to gutta-percha, where the maximum bond was shown by
      subgroup 3b, EndoRez. CONCLUSION: Under the circumstances of this in vitro study,
      all the six endodontic sealers had significant differences in terms of shear bond
      strength to gutta-percha and dentin.

PMID- 20142882
TI  - Alginate impressions: A practical perspective.
AB  - The choice of an impression material for a particular situation depends on the
      treatment being provided, operator preference, and so on. Even with the
      introduction of more advanced and more accurate rubber base impression materials,
      irreversible hydrocolloid impression materials have stood the test of time. This
      article gives a detailed perspective of how best to make alginate impressions.

PMID- 20142884
TI  - Problem based learning....Need for the hour.

PMID- 20142883
TI  - Retrieval of a separated instrument using Masserann technique.
AB  - The fracture of endodontic instruments is a procedural problem creating a major
      obstacle to normal routine therapy. The separated instrument, particularly a
      broken file, leads to metallic obstruction in the root canal and impedes
      efficient cleaning and shaping. When an attempt to bypass such a fragment becomes
      difficult, it should be retrieved by mechanical devices. Masserann kit is one
      such device for orthograde removal of intracanal metallic obstructions. These
      clinical cases demonstrate the usage of Masserann technique in removal of
      separated instruments in anterior and also the posterior teeth.

PMID- 20142885
TI  - The monk who wants to sell his zen...

PMID- 20142887
TI  - Fiber optic backscatter spectroscopic sensor to monitor enamel demineralization
      and remineralization in vitro.
AB  - In this study, a Fiber Optic Backscatter Spectroscopic Sensor (FOBSS) is used to
      monitor demineralization and remineralization induced changes in the enamel. A
      bifurcated fiber optic backscatter probe connected to a visible light source and
      a high resolution spectrophotometer was used to acquire the backscatter light
      spectrum from the tooth surface. The experiments were conducted in two parts. In
      Part 1, experiments were carried out using fiber optic backscatter spectroscopy
      on (1) sound enamel and dentine sections and (2) sound tooth specimens subjected
      to demineralization and remineralization. In Part 2, polarization microscopy was
      conducted to examine the depth of demineralization in tooth specimens. The enamel
      and dentine specimens from the Part-1 experiments showed distinct backscatter
      spectra. The spectrum obtained from the enamel-dentine combination and the
      spectrum generated from the average of the enamel and dentine spectral values
      were closely similar and showed characteristics of dentine. The experiments in
      Part 2 showed that demineralization and remineralization processes induced a
      linear decrease and linear increase in the backscatter light intensity
      respectively. A negative correlation between the decrease in the backscatter
      light intensity during demineralization and the depth of demineralization
      determined using the polarization microscopy was calculated to be p = -0.994.
      This in vitro experiment highlights the potential benefit of using FOBSS to
      detect demineralization and remineralization of enamel.

PMID- 20142886
TI  - The periodontal - endodontic continuum: A review.
AB  - Periodontal therapy deals with many aspects of the supporting structures,
      including the prevention and repair of lesions of the gingival sulcus.
      Endodontics deals primarily with disease of the pulp and periapical tissues. The
      success of both periodontal and endodontic therapy depends on the elimination of
      both disease processes, whether they exist separately or as a combined lesion.
      The relationship between periodontal and endodontic disease has been a subject of
      speculation for many years. This paper aims at presenting a comprehensive review
      of several aspects of perio-endo lesions.

PMID- 20142888
TI  - An evaluation and comparison of shear bond strength of composite resin to dentin,
      using newer dentin bonding agents.
AB  - The purpose of this study was to assess the shear bond strength of Total etch
      Prime and Bond NT and self etch newer dentin bonding agents Clearfil S3, Xeno III
      Bond, Clearfil Protect Bond and G Bond used to bond composite resin to dentin,
      and to compare the difference in the shear bond strengths of the self etch newer
      dentin bonding agents. Hundred freshly extracted noncarious human maxillary
      premolar teeth were selected. The occlusal surfaces of each tooth were ground to
      prepare flat dentin surfaces at a depth of 1.5 mm and were randomly grouped, with
      twenty specimens in each: Group I - Prime and Bond NT, Group II - Clearfil
      Protect Bond, Group III - Xeno III Bond, Group IV - Clearfil S3 Bond, Group V - G
      Bond. Each group was treated with its respective bonding agents, as per the
      manufacturers' instructions Clearfill - Kuraray, Japan, G bond - GC Tokyo, Japan,
      Xeno- De Trey Densply, Germany. Blocks or Cylinders of composite resin were built
      up using Teflon mold and cured. Shear bond strengths were tested using Instron
      Universal testing machine and recorded in Mpa. The results were statistically
      analyzed using One-way anova and Tukeys HSD test. The total etch adhesive showed
      higher shear bond strength than self etching adhesives (P < 0.001). Within the
      limitations of this in vitro study, it can be concluded that all the adhesive
      agents evaluated showed optimal shear bond strength 17-20 Mpa, except G bond.
      However, shear bond strength of composite resin to dentin is better with one
      bottle total etch adhesive than with the newer self etching bonding agents.

PMID- 20142889
TI  - Evaluation of depth of cure and knoop hardness in a dental composite, photo
      activated using different methods.
AB  - The study aimed at evaluating the depth of cure and knoop hardness of a microfine
      hybrid composite resin that was photo-activated using different methods. A
      bipartite brass mold was filled with composite resin and photo-activation was
      performed using four methods: (1) Intermittent method using quartz tungsten
      halogen (QTH) light curing unit (LCU) (2) Continuous method (QTH) (3) Exponential
      method (QTH) (4) Continuous method using light-emitting diode (LED). Depth of
      cure was measured at the unexposed bottom surface of the specimen using
      microtester as a penetrometer. The surfaces exposed to light were subjected to
      knoop hardness testing, using a digital microhardness tester. Knoop hardness
      measurements were obtained at the top surface and at depths of 1, 2, 3, 4 and 5
      mm. The data was analyzed using anova and Tukey's test (5%). Results showed that
      the depth of cure was higher with the intermittent method (QTH), followed by the
      continuous method (QTH), the exponential method and the continuous method (LED).
      At the top surface and up to 1 mm, continuous method (LED) demonstrated the
      highest knoop hardness number (KHN). At 2 mm and up to 5 mm, intermittent method
      (QTH) presented the highest KHN and continuous method (LED) showed the lowest
      KHN. At all depths, continuous method (QTH) showed higher KHN, as compared to the
      exponential method (QTH), except at 2 mm where both showed no significant
      difference.

PMID- 20142890
TI  - In vitro evaluation of the accuracy of two electronic apex locators.
AB  - This study involves evaluating the accuracy of two electronic apex locators
      (EALs), Raypex and Neosono Co-pilot. Ten single-root human anterior teeth were
      used for the study. The crown was sectioned to gain access to the root canal. For
      each tooth, the reference (or control) length, corresponding to the actual
      length, was determined, after which all the teeth were measured independently.
      The results obtained with each EAL were in turn compared with the corresponding
      control length. The statistical analysis of the results showed that EAL
      reliability in detecting the apex varies from 80 to 85% for Neosono systems and
      85 to 90% for the Raypex systems. Combined with a high observer concordance,
      these results suggest that electronic root canal measurement can be an objective
      and acceptably reproducible technique.

PMID- 20142891
TI  - The effect of McInnes solution on enamel and the effect of Tooth mousse on
      bleached enamel: An in vitro study.
AB  - AIMS: To evaluate the effect of McInnes bleaching agent on the micro hardness of
      enamel before and after bleaching and to evaluate the effect of G C Tooth Mousse
      on the bleached enamel surface for its microhardness. MATERIALS AND METHODS:
      McInnes bleaching solution, Casein phosphopeptide-amorphous calcium phosphate CCP
      ACP (G C Tooth mousse) artificial saliva (Dept of Oral Pathology, College of
      Dental Sciences, Davengere), deionized water, Vickers Micro Hardness tester
      (Zwick/ZHV, Germany), freshly extracted teeth, cold cure acrylic, Diamond disc
      (Horico - PFINGST New jersey USA, KAVO- Germany), straight handpiece (kavo peca
      reta) and plastic moulds (6.5 x 2 mm). The purpose of this study was to evaluate
      and compare microhardness of the sound enamel surface by Vickers Hardness Number
      before and after bleaching with McInnes solution, and to evaluate the effect of
      casein phosphopeptide amorphous calcium phosphate (G C Tooth Mousse) on the
      bleached enamel surface for its microhardness. STATISTICAL ANALYSIS: The data
      obtained from the test were subjected for statistical analysis and are presented
      as range, mean and standard deviation. P value of 0.05 or less was considered for
      statistical significance. The changes in microhardness at different times of
      assessment were analyzed using the paired 't' test RESULTS: All the samples
      showed decrease in the microhardness after two cycles of bleaching, though
      immediately after bleaching the decrease in the microhardness was not significant
      (P = 0.34). However, after the second cycles, it showed a significant decrease
      (P<0.01) in the microhardness. After application of remineralization solution (GC
      Tooth mousse), the samples showed a marginal increase in the microhardness
      (P<0.05) after seven days and a marked increase after fourteen days (P<0.001).
      CONCLUSION: McInnes bleaching agent does decrease the microhardness of enamel by
      causing enamel demineralization and GC Tooth mousse used in the study causes an
      increase in the microhardness of bleached enamel by maintaining a high gradient
      of calcium and phosphate ions at the enamel subsurface.

PMID- 20142892
TI  - Biphasic calcium phosphate in periapical surgery.
AB  - Calcium phosphate ceramics like hydroxyapatite and beta -tricalcium phosphate
      (beta -TCP) possess mineral composition that closely resembles that of the bone.
      They can be good bone substitutes due to their excellent biocompatibility.
      Biphasic calcium phosphate is a bone substitute which is a mixture of
      hydroxyapatite and beta -tricalcium phosphate in fixed ratios. Studies have
      demonstrated the osteoconductive potential of this composition. This paper
      highlights the clinical use of biphasic calcium phosphate as a bone substitute in
      periapical surgery.

PMID- 20142893
TI  - Mind over matter.

PMID- 20142894
TI  - Time to conserve... Conservative dentistry?

PMID- 20142895
TI  - Is it the end of the road for dental amalgam? A critical review.
AB  - The longevity of dental restorations is dependent on many factors, including
      those related to materials, the dentist, and the patient. Dental amalgams have
      successfully served the profession for over a century. The main reasons for
      restoration failure are secondary caries, fracture of the bulk of the restoration
      or of the tooth, and marginal deficiencies and wear. The importance of direct
      placement, aesthetic, tooth-colored restorative materials is still increasing.
      Amalgam restorations are being replaced because of alleged adverse health effects
      and inferior aesthetic appearance. All alternative restorative materials and
      procedures, however, have certain limitations. This article will attempt to
      critically analyse both amalgams and resin based composites, through an
      evaluation of scientific literature.

PMID- 20142896
TI  - Evaluation of weight change in three different light cured composite restorative
      materials stored in water: An in vitro study.
AB  - AIMS AND OBJECTIVES: The objective of this in vitro study was to investigate
      whether weight gain in three different composites occurs due to water absorption,
      when stored in water. MATERIALS AND METHODS: The composite restorative materials
      selected for this study included a micro-fine hybrid (Synergy) and two nano
      filled composites (CERAM X duo and FILTEK Z 350). Twenty specimens of each
      material were fabricated with each composite material.- Group A: Filtek Z 350,
      Group B: Synergy, and Group C: CERAM X Duo. Then all the specimens were stored in
      10 ml distilled water in test tubes, and then placed in an incubator at 37oC for
      six weeks. The weight changes of these specimens were measured daily for the
      first week, and, later, once a week, for the next five weeks, by using an
      electrical analytical balance. RESULTS: The data were analyzed using one-way
      analysis of variance and Student 't' test. There was a tendency for the weight of
      the specimens to increase with the passage of time, when stored in water. All the
      groups showed maximum amount of water absorption in the first week; then there
      was a gradual decrease in the water absorption, from the second to the sixth
      week. Synergy showed the maximum amount of water absorption in the first week, as
      compared to FILTEK Z 350 and Ceram X Duo. However, FILTEK Z 350 showed the
      maximum amount of water absorption from the second week to the sixth week, as
      compared to Ceram X Duo and Synergy. CONCLUSION: All composite restorative
      materials absorb some amount of water. The water absorption of the composite may
      decrease the physical and mechanical properties of the composites; hence, it is
      necessary to consider the type of the material before starting treatment.

PMID- 20142897
TI  - The influence of different composite placement techniques on microleakage in
      preparations with high C- factor: An in vitro study.
AB  - OBJECTIVE: This study evaluated the marginal leakage around class-I cavity
      preparations restored with Nanofilled composite (Filtek Z-350 A2 shade, 3M ESPE,
      USA) and a self-etch adhesive (Xeno III, DENTSPLY/Caulk) using different
      composite placement techniques. MATERIALS AND METHODS: Standardized class-I
      cavities were prepared on 36 caries-free, extracted human premolars and were
      randomly assigned to three groups: (1) Horizontal incremental curing was done;
      each increment of thickness 1.5 mm was cured one after the other using curing
      unit (T-LED, Elca Technology, Italy). (2) Concave surface was obtained with a
      ball burnisher on the first increment and cured for 20 seconds; subsequently, the
      next increment was placed and similarly cured. (3) Cavities were filled with
      resin, short of the occlusal surface; two cuts (mesiodistal and buccolingual)
      were made through the condensed resin and cured for 20 seconds, followed by
      addition of resin in the gaps created by the cuts and additional curing for 20
      seconds. The specimens were stored in distilled water for three months and then
      subjected to thermocycling, followed by immersion in 0.5% methylene blue dye for
      24 hours. The teeth were sectioned longitudinally and evaluated for microleakage
      under stereomicroscope, and the scores obtained were analysed with Fisher Exact
      test and Kruskal-Wallis nonparametric test. RESULTS: There was no statistically
      significant difference among three groups. CONCLUSION: None of the techniques was
      capable of eliminating the microleakage in preparations with a high C-factor.

PMID- 20142898
TI  - The effect of occlusal restoration and loading on the development of abfraction
      lesions: A finite element study.
AB  - BACKGROUND: Abfraction, a type of non-carious cervical tooth loss, is a poorly
      understood condition. One factor thought to contribute to the development of
      these lesions is the effect of occlusal loading and the presence of occlusal
      restoration. AIM AND OBJECTIVES: The aim of this paper is to study the stress
      profile in the cervical region of mandibular first premolar with variation of
      occlusal loads, and to compare the stress profile between sound and occlusally
      restored tooth under variation of occlusal load, using two-dimensional plane
      strain finite element model. MATERIALS AND METHODS: A mandibular first premolar
      was sectioned and modeled in the finite element software, along with its
      peridontium. Varying occlusal loads were applied along the cuspal inclines, with
      and without an occlusal restoration. The software used was NISA II EMRC. RESULT:
      It was found that higher occlusal loads caused more cuspal flexure and that the
      maximum shear stress was much higher and closer to the cervical area. It was also
      observed that there was a slight increase in shear stress when occlusal
      restoration was present. CONCLUSION: It was suggested that high occlusal loading
      and the presence of an occlusal amalgam restoration increased the stress
      concentration at the cervical area, which may lead to the breakdown of enamel at
      the cervical region.

PMID- 20142899
TI  - Finite element analysis of stress concentration in Class V restorations of four
      groups of restorative materials in mandibular premolar.
AB  - AIM: To study the concentration of stress in class V restoration of four
      different restorative materials subjected to occlusal load of 100N, 150N, 200N,
      250N and to analyse the obtained data with the listed properties of the
      restorative material. MATERIALS AND METHODS: Using FEM analysis the stresses
      generated in a class V lesion in a mandibular premolar was studied. RESULTS:
      Within the framework of the aforementioned views, and from the results of the
      study it can be concluded that microfilled composite is the most suitable
      restorative material followed by flowable composite, glass ionomer cement and
      resin modified glass ionomer cement. CONCLUSION: Restoration of Class V lesions
      with materials of higher modulus of elasticity will enable better stress
      distribution.

PMID- 20142900
TI  - The influence of salivary contamination on the shear bond strength of two newer
      generation dentin bonding agents - An in vitro study.
AB  - BACKGROUND AND OBJECTIVES: To investigate whether salivary contamination during
      various stages of the bonding procedures of Xeno III and Clearfil SE Bond
      influences shear bond strength. MATERIALS AND METHODS: THE OCCLUSAL SURFACES OF
      THIRTY SIX MAXILLARY PREMOLAR TEETH WERE GROUND AND DIVIDED INTO TWO GROUPS
      CONTAINING EIGHTEEN SPECIMENS EACH, WHICH WAS SUBDIVIDED INTO THREE SUB GROUPS:
      Group I - Xeno III, Group II - Clearfil SE Bond, Subgroup A - Uncontaminated
      (control), Subgroup B - Contaminated with saliva before application and light
      curing, Subgroup C - Contaminated with saliva after light curing. Composite resin
      Filtek Z350 was packed using Teflon mold cured and subjected to shear bond
      strength analysis using universal Instron machine. RESULTS: Statistical analysis
      was made using One-way ANOVA and Tukeys HSD test. Clearfil SE Bond showed very
      high statistically significant reduction in the bond strength, when salivary
      contamination took place after light curing; whereas, Xeno III showed very high
      statistically significant reduction when salivary contamination took place before
      application and light curing. CONCLUSION: Clearfil SE Bond showed more tolerance
      to salivary contamination of dentin and higher shear bond strength value, when
      compared to Xeno III.

PMID- 20142901
TI  - Rehabilitation of gingival architecture by a conservative method: An innovative
      approach.
AB  - Periodontal attachment loss in the maxillary anterior region can often lead to
      esthetic and functional clinical problems. Lifelong motivation is essential to
      the supportive therapy for these patients, and the maintenance of good esthetics,
      combined with conducive to maintaining long term dental and professional health.
      This paper aims to demonstrate an innovative treatment option for dealing with
      aesthetic challenges posed by a number of patients who have undergone initial
      cause related therapy for aggressive periodontitis.

PMID- 20142902
TI  - Psychiatric issues in renal failure and dialysis.
AB  - This article aims to bring to the fore, issues regarding the interface of
      psychiatry and renal failure. Depression, anxiety, suicide and delirium are
      common complications observed in patients with renal failure. Pharmacological
      management of these problems need stringent monitoring on part of the
      psychiatrist. This article examines the various complications that may be
      observed in patients with renal failure while discussing treatment approaches and
      also emphasizing the need for interdisciplinary team work in improving the
      quality of life of patients with renal failure and those on dialysis.

PMID- 20142903
TI  - Prophylactic effects of Wormwood on lipid peroxidation in an animal model of lead
      intoxication.
AB  - The ability of Wormwood (Artemisia absinthium L.) extract (A.Ab) to restore
      membrane-bound enzymes like Na(+)-K(+)-ATPase, Ca(++)-ATPase, Mg(++)-ATPase, and
      oxidative damage induced by lead were investigated. Rats were exposed to lead
      acetate (750 ppm) for 11-weeks and treated during 4-weeks with A.Ab. Lipid
      levels, ATPase activity, thiobarbituric acid reactive substances (TBARS), and
      proteins carbonyl were estimated. In liver and kidney, lead acetate inhibited
      membrane-bound enzymes and increased (P < 0.05) the levels of cholesterol,
      triglycerides, free fatty acids, phospholipids, TBARS, and carbonyl proteins.
      After 4 weeks, the intoxicated group who received A.Ab showed a significant
      reduction in TBARS and carbonyl levels in liver and kidney compared to group
      exposed to lead. A.Ab restored the levels of membrane-bound enzymes and lipid
      levels to near normal. These results indicate that aqueous Wormwood extract had a
      significant antioxidant activity and protect liver and kidney from the lead
      induced toxicity.

PMID- 20142904
TI  - Monascus purpureus Went rice in nephrotic hyperlipidemia.
AB  - BACKGROUND: Nephrotic dyslipidemia is a risk factor for the development of
      systemic atherosclerosis; and may aggravate glomerulosclerosis and enhance
      progression of glomerular disease. We aimed to assess the efficacy and safety of
      Monascus purpureus Went rice vs. fluvastatin therapy in the management of
      nephrotic dyslipidemia. MATERIALS AND METHODS: Seventy-two patients with
      persistent idiopathic nephrotic syndrome (NS) with secondary dyslipidemia were
      included. They were randomly allocated into three age and sex-matched groups. The
      first group comprised 20 cases and were given M. purpureus Went rice in a dose of
      600 mg twice/day for 1 month then once daily, the second group comprised 30 cases
      were given fluvastatin in a daily dose of 20 mg. The remaining 22 received no
      antidyslipidemic therapy and constituted a control group. All of these patients
      were subjected to thorough laboratory investigations including renal function
      tests and lipogram. Moreover, the neuromuscular status was evaluated with
      electromyography and nerve conduction velocity. RESULTS: Our results showed that
      both fluvstatin and M. purpureus Went rice were well tolerated with no evidence
      of significant side effects including neuromuscular functions. Both of them
      significantly reduced cholesterol after 6 months and 1 year. CONCLUSION: Monascus
      purpureus Went rice is safe, effective, and economic treatment strategy for
      nephrotic dyslipidemia.

PMID- 20142905
TI  - Thickness of glomerular and tubular basement membranes in preclinical and
      clinical stages of diabetic nephropathy.
AB  - AIMS: This study aimed to elucidate the early renal changes in diabetes mellitus
      (DM) with and without clinical symptoms related to renal damage. METHODS: Renal
      biopsy was studied in 25 patients (14 with microalbuminuria and 11 with
      albuminuria) both by light and electron microscopies (LM and EM, respectively)
      for renal changes and morphometry was performed to study glomerular and tubular
      basement membranes (GBM and TBM, respectively) width using a Soft Imaging System
      GmBH (analysis 3). RESULTS: A significant increase was noted in the mean GBM and
      TBM thickness in both the preclinical and clinical groups compared to the control
      group. The changes in the TBM were noted to be predominant in both preclinical
      and clinical patients. CONCLUSIONS: This study indicates the importance of
      morphometric evaluation of the GBM and TBM width in the elucidation of early
      renal damage in diabetic nephropathy, especially in the absence of LM changes.
      The significance of identification of early renal changes using morphometric
      techniques for better management of these patients requires further studies.

PMID- 20142906
TI  - Nephrogenic fibrosing dermatopathy, cardiac calcification and pulmonary
      hypertension in an adolescent on chronic hemodialysis.
AB  - Nephrogenic fibrosing dermatopathy (NFD) is a systemic disorder of unknown
      etiology. Recent reports have associated the development of NFD with the use of
      gadolinium-enhanced magnetic resonance imaging (MRI). Here, we present the case
      of an adolescent with end-stage renal disease who died of biopsy-proven NFD and
      also developed cardiac calcification and clinical manifestations of pulmonary
      fibrosis with pulmonary hypertension. Only five cases of NFD have been reported
      in children, all of which were prior to the information regarding the
      consequences of using gadolinium. Here, we report a patient with NFD who received
      gadolinium while on chronic hemodialysis, 16 months prior to the onset of
      symptoms. Because he succumbed to this disease, we stress on the importance of
      eliminating the use of gadolinium-enhanced MRI examinations in children with
      impaired kidney function until the etiology of NFD is clarified.

PMID- 20142907
TI  - Thrombotic microangiopathy with severe renal failure in adenocarcinoma.
AB  - Kidney disease frequently complicates malignancy and its treatment. The spectrum
      of renal disease in cancers includes acute kidney injury, chronic kidney disease
      and tubular disorders. Thrombotic microangiopathy (TMA) is an uncommon initial
      clinical presentation of malignancies. Renal failure is an extremely rare feature
      of cancer-associated TMA syndromes in the absence of chemotherapy. Here, we
      report a patient who presented to the hospital for the first time with TMA and
      severe renal failure requiring hemodialysis and was diagnosed with gastric
      adenocarcinoma.

PMID- 20142908
TI  - Acute renal failure associated with nonfulminant acute viral hepatitis A.
AB  - Hepatitis A runs a benign course in children, but may have atypical presentations
      in adults. Very rarely acute renal failure complicates nonfulminant hepatitis A.
      We report a patient with nonfulminant acute viral hepatitis A with multiorgan
      involvement. Patient had biopsy proven acute interstitial nephritis, acute
      pancreatitis, acute myocarditis and required hemodialysis for 6 weeks.

PMID- 20142909
TI  - Membranoproliferative glomerulonephritis with essential cryoglobulinemia.
AB  - Cryoglobulinemia is an uncommon cause of renal disease and often occurs in
      patients with hepatitis C virus (HCV) infection. We report a case of
      membranoproliferative glomerulonephritis in a patient with cryoglobulinemia,
      which was not associated with HCV infection or any identifiable etiology.

PMID- 20142910
TI  - Arteriovenous fistula following kidney biopsy.

PMID- 20142911
TI  - Effect of taurine and acetylcysteine in attenuating microalbuminuria in type 2
      diabetes.

PMID- 20142912
TI  - A case of fever and unexplained acute renal failure.

PMID- 20142913
TI  - Aquaporins: The renal water channels.
AB  - Water is the most abundant molecule in any cell. Specialized membrane channel,
      proteins called aquaporins, facilitate water transport across cell membranes. At
      least seven aquaporins (AQP): 1, 2, 3, 4, 6, 7, and 11 are expressed in the
      kidneys. Aquaporins play a role in both the short-term and long-term regulation
      of water balance as well as in the pathophysiology of water balance disorders.
      Aquaporin is composed of a single peptide chain consisting of approximately 270
      amino acids. Inherited central and nephrogenic diabetes insipidus are primarily
      due to the decreased expression of AQP2 while mutation in the AQP2 molecule is
      responsible for inherited central diabetes insipidus. In acquired causes of
      nephrogenic diabetes insipidus, there is a downregulation of AQP2 expression in
      the inner medulla of the kidney. Nephrotic syndrome is characterized by excessive
      sodium and water reabsorption, although in spite of this, patients do not develop
      hyponatremia. There is a marked downregulation of both AQP2 and AQP3 expression,
      which could be a physiologic response to extracellular water reabsorption in
      patients with nephrotic syndrome. There are some conditions in which aquaporin
      expression has been found to increase such as experimentally induced heart
      failure, cirrhosis, and pregnancy. Some drugs such as cisplatin and cyclosporine,
      also alter the expression of aquaporins. The three-pore model of peritoneal
      transport depicts the importance of aquaporins. Thus, the understanding of renal
      water channels has solved the mystery behind many water balance disorders.
      Further insights into the molecular structure and biology of aquaporins will help
      to lay a foundation for the development of future drugs.

PMID- 20142914
TI  - Serum magnesium in recovering acute renal failure.
AB  - We studied the manifestations of hypomagnesemia in 50 patients with acute renal
      failure who had been admitted in our hospital over a period of ten months. All
      patients with serum creatine >/= 2 mg/dL and normal baseline levels of serum
      calcium, magnesium, and potassium as well as normal ECG were included in the
      study. Patients with multi-organ failure, drug-induced acute renal failure,
      obstructive uropathy, and alcohol addiction were excluded. The mean age of our
      study population was 40 +/- 15 years, 37 of the patients were male and 13 were
      female. Hypomagnesemia was observed in 31 patients out of 50 during the recovery
      period of acute renal failure with symptomatic hypomagnesemia being seen in 23
      patients. Serum magnesium levels on the day of admission and during the recovery
      phase were 2.11 +/- 0.38 mg/dL and 1.64 +/- 0.41 mg/dL respectively. Paresthesia,
      irritability, agitation, dysartharia, vertigo, and associated hypokalemia and
      hypocalcemia were noted in symptomatic hypomagnesemic patients. Treatment of
      hypomagnesaemia and hypokalemia ameliorated the symptoms. We conclude that these
      abnormalities produce clinically significant manifestations in recovery phase of
      acute renal failure and clinicians should pay attention to these.

PMID- 20142915
TI  - Relationship between serum leptin level and laboratory and anthropometric indices
      of malnutrition in patients on hemodialysis.
AB  - Protein-energy malnutrition is a major problem and one of the risk factors for
      mortality in hemodialysis patients. There is no single index in evaluation of
      nutritional status in these patients, so leptin can be used as one of the
      parameters. In this study, the correlation between serum leptin with biochemical
      and anthropometric parameters of nutrition has been evaluated. This cross
      sectional study has been performed on 60 hemodialysis patients (32 males and 28
      females) in 2006. The patients on hemodialysis for under 1 year and who has a
      history of consumption of lipid lowering agents or glucocorticoids, or an
      infectious or inflammatory disease were excluded. Malnutrition laboratory
      parameters and serum leptin were measured before hemodialysis. Serum leptin was
      measured with enzyme-linked immunosorbent assay (ELISA) method with direct dbc
      kit and malnutrition laboratory parameters measured with standard laboratory
      methods, patients anthropometric parameters evaluated after hemodialysis. The
      mean age of patients was 47.5 +/- 16.1 years and the range of serum leptin level
      was 0.6-64.8 ng/ml. Mean serum leptin level were 22.64 +/- 19.54 ng/ml in females
      and 16.74 +/- 20.16 ng/ml in males on hemodialysis and in spite of higher level
      of leptin in females there was not any statistically significant difference
      between females and males serum leptin. Absolute value of correlation coefficient
      between serum leptin and anthropometric parameters and most laboratory parameters
      was < 0.25 (except ferritin, iron, phosphorous in males and total protein,
      hemoglobin, urea, and creatinin in females which was between 0.25 and 0.50). Our
      results suggest that the increased serum leptin level does not have a major role
      in diagnosis of malnutrition in hemodialysis patients and there is a poor
      correlation between malnutrition parameters and serum leptin level.

PMID- 20142916
TI  - Prevalence of microalbuminuria and its risk factors in type 2 diabetic patients.
AB  - A cross-sectional study was performed from November 2005 to July 2007 to
      determine the prevalence of microalbuminuria and its risk factors among type 2
      diabetic patients.. Two hundred and eighty-eight type 2 diabetic patients (141
      males and 147 females) referred to Yazd diabetes research center were randomly
      recruited for the study. Microalbuminuria was detected by measuring the albumin
      to creatinine ratio in the early morning urine. Microalbuminuria was diagnosed if
      this ratio was between 30 and 300 mg/g on two occasions during three months.
      Prevalence of microalbuminuria was 14.2%. Chi-square analysis revealed that
      microalbuminuria was correlated with the diastolic blood pressure (P = 0.003) and
      the duration of diabetes (P = 0.000). No statistically significant correlation
      was found between microalbuminuria and age, sex, body mass index, levels of
      fasting blood sugar, glycosylated hemoglobin (HbA1c), serum triglyceride, and
      serum cholesterol, or systolic blood pressure. For 240 patients for whom the
      duration of diabetes was known from the answers in their questionnaires, logistic
      regression was used for analysis. Results showed that two variables including the
      duration of diabetes and Diastolic Blood Pressure (DBP) play a role in this model
      and the following Logic association was obtained: g; (x) = -9.233 +/- 0.079 DBP
      +/- 0.114 duration according to this model, both DBP and duration of diabetes
      were directly correlated with microalbuminuria. Determination of the urine
      albumin to creatinine ratio is an easy method for screening of microalbuminuria
      that is suggested for all diabetic patients, especially diabetic patients with
      hypertension and long-term diabetes.

PMID- 20142917
TI  - Utility of C-2 (Cyclosporine) monitoring in postrenal transplant patients: A
      study in the Indian population.
AB  - The study was planned and conducted to assess the benefit of C-2 levels (blood
      cyclosporine levels two hours postdosing) monitoring over trough (C0) levels
      (predosing) in postrenal transplant patients. The patient population included 34
      postrenal transplant individuals (28 males and six females, mean age of 39.9 +/-
      12.3 years). The patients were first-transplant patients and were receiving a
      microemulsion form of cyclosporine A (CsA) as an immunosuppressant along with
      azathioprine and prednisolone. In addition, they were not on any enzyme
      inducer/inhibitor drugs, except for diltiazem. Timed collection of C0 and C-2
      samples was done and the samples were immediately processed using the cedia
      cyclosporine plus assay kit. Estimation was done on a Beckman synchron CX5CE
      fully automated chemistry analyzer. Serum urea nitrogen and creatinine levels
      were checked. Poor graft survival was found in this population with 29.3%
      patients showing graft rejection. The graft rejection patients were assigned to
      two groups: group I with chronic graft rejection patients (17.6%) and group II
      with acute graft rejection patients (11.7%). Group III consisted of graft
      survival patients (70.7%). Mean +/- SD was calculated for C0 and C2 levels.
      Individual values for C0 and C-2 were plotted on a scatter chart. C0 and C-2
      levels were normalized by calculating them as the percentage of their targets
      (data not shown) and compared using the Kruskal Wallis one-way analysis of
      variance. C0 levels in all the three groups were within the recommended
      therapeutic range (150-300 ng/mL) (P < 0.182). Blood C-2 concentrations did not
      achieve the recommended target levels in these patients. One-way analysis of
      variance for C-2 values when expressed as the percentage of the target values did
      not show any significant difference between these groups (P < 0.84). No
      significant difference was found in C0 levels between groups I, II, and group III
      patients when expressed as the percentage of the target values (P < 0.182). The
      mean serum urea nitrogen level was 26.4 +/- 8.1 mg/dL whereas the mean serum
      creatinine level was 1.79 +/- 0.8 mg/dL. As is evident in the present study, the
      target C2 levels of cyclosporine dosage were not achieved whereas the C0 levels
      in all the three groups were within the optimum therapeutic range. As the
      incidence of graft dysfunction was also proportionately high, the importance of
      C2 monitoring is further highlighted on the basis of this study The contributory
      factors for levels lower than the target levels, such as the use of low doses of
      cyclosporine and interacting drugs should be carefully monitored in clinical
      practice. The achievement of optimum levels of C-2 may help in reducing the
      higher incidence of graft rejection in these patients. This practice is of equal
      importance in reducing cyclosporine-related renal toxicity, a rather irreversible
      process.

PMID- 20142918
TI  - Tumoral calcinosis (Teutschlander disease) in a dialysis patient.
AB  - Tumoral calcinosis is an uncommon and severe complication of hemodialysis
      therapy. It is generally associated with the presence of the high serum calcium
      and-phosphorus product. We report here a case of a patient on hemodialysis who
      presented with progressively increasing, multiple, tumor-like, subcutaneous
      swellings. These are rare manifestations of extraosseous calcification in uremic
      patients that are termed as tumoral calcinosis. A 25 year-old male presented with
      multiple, nodular, painful, cutaneous swellings all over his body that had been
      progressively increasing over the last four years. He was a known case of chronic
      glumerulonephritis who was on regular hemodialysis. The patient was investigated
      and diagnosed as having tumoral calcinosis and was treated with a low calcium
      dialysate of pure reverse osmosis water.

PMID- 20142919
TI  - Vitamin D intoxication presenting as acute renal failure.
AB  - A 70 year-old male presented with acute renal failure and mental obtundation. On
      examination, he was found to have hypercalcemia and on further questioning, it
      was found that it was secondary to injections of a slow-release vitamin D
      preparation. Although total body exposure is sufficient for vitamin D synthesis,
      increased vitamin D deficiency secondary to poor exposure to sunlight is observed
      in some parts of the world. We report here a case of vitamin D intoxication from
      the Kashmir valley where vitamin D deficiency is 100% in the general population
      that is confined indoors.

PMID- 20142920
TI  - Recurrent hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) is an uncommon cause of acute renal failure.
      Diarrhea-associated (D+) HUS, usually seen in children, is a common variety of
      HUS. HUS that is not associated with diarrhea (D-) is caused by a heterogeneous
      group of disorders. We report here a case of recurrent HUS (D-) in an adult
      female with hypocomplementemia.

PMID- 20142921
TI  - Leptospirosis with acute renal failure and paraparesis.
AB  - Leptospirosis is an important zoonosis with a worldwide distribution that is
      characterized by a broad spectrum of clinical manifestations ranging from
      inapparent infection to fulminant disease. The presentation of paraparesis in
      combination with acute renal failure is rare.

PMID- 20142922
TI  - Color Doppler findings of post-biopsy arteriovenous fistula in renal transplant.
AB  - Post biopsy arterio-venous fistula in renal transplant range in incidence from 15
      16%. Spontaneous resolution of 75% A-V fistulas is seen within four weeks. We
      report a patient with post biopsy arterio-venous fistula who had developed
      unexplained hypertension with no definite feature of rejection on biopsy. Doppler
      application revealed an arterio-venous fistula which showed spontaneous
      resolution in six weeks.

PMID- 20142923
TI  - The veiled right kidney sign.

PMID- 20142924
TI  - The declaration of Istanbul on organ trafficking and transplant tourism.

PMID- 20142925
TI  - An assessment of the quality of life in hemodialysis patients using the WHOQOL
      BREF questionnaire.
AB  - A cross-sectional study was conducted to evaluate the quality of life (QOL) of
      hemodialysis patients. An attempt was made to compare the QOL of hemodialysis
      patients with the QOL of the general population, renal transplant patients, and
      patients with a chronic disease, in this case, asthma. The WHOQOL-BREF
      questionnaire was used to assess the quality of life. Hemodialysis patients who
      had completed three months of maintenance hemodialysis (n = 75) were enrolled
      into the study. The quality of life of hemodialysis patients was found to be
      significantly impaired (P < 0.05) in comparison to healthy individuals of the
      general population, particularly with respect to the physical, psychological, and
      social relationship domains. In comparison to the quality of life of renal
      transplant patients, the quality of life of hemodialysis patients was
      significantly (P < 0.05) lower in all the four WHOQOL-BREF domains. Only in the
      environmental dimension was the quality of life of hemodialysis patients found to
      be significantly lower than that of the asthma patients. Female hemodialysis
      patients showed significantly (P < 0.05) lower quality of life than did male
      patients in the psychological and environmental dimensions of WHOQOL-BREF. A
      positive association was seen between higher education and the psychological
      functioning and the environmental dimensions of WHOQOL-BREF. Thus, the quality of
      life of hemodialysis patients was found to be considerably impaired when compared
      to that of healthy individuals of the general population as well as of renal
      transplant patients.

PMID- 20142926
TI  - Determination of urinary peptides in patients with proteinuria.
AB  - Although considered useful in the diagnosis and prognosis of renal diseases,
      proteinuria can only be detected after significant renal paranchymal changes.
      There is considerable interest in the estimation of urinary peptides as an early
      marker of renal disease. In the current study, we have estimated urinary peptides
      in patients with different grades of proteinuria. Twenty-four hour urine samples
      were collected from 138 subjects and classified into three groups based on the
      urine protein excreted: group I (normoproteinuria, 0-150 mg/day, n = 37), group
      II (microproteinuria, 150-300 mg/day, n = 31), and group III (macroproteinuria, >
      300 mg/day, n = 70). Urine proteins were determined using Bradford's method and
      urinary peptide levels were determined by subtracting Bradford's value from the
      Lowry value of the same sample. There was a significant decrease in the levels of
      urinary peptides in group III compared to group I (P < 0.01), however, there was
      no difference in peptides between groups I and II. The percentage of urinary
      peptides was decreased in both groups II and III compared to group I (P < 0.01),
      and there was a significant difference in % urinary peptide content in group II
      compared to group III (P < 0.01). On correlation, % urinary peptides correlated
      negatively with urinary proteins/g creatinine (r = - 0.782, P < 0.01) and
      positively with urinary peptides/g creatinine (r = 0.238, P < 0.01). Our data
      suggest that there is a marked decrease in urinary peptide levels with an
      increase in proteinuria. This may suggest impaired tubular protein reabsorption
      and degradation capacity of renal tubules.

PMID- 20142927
TI  - Effect of cryotherapy on arteriovenous fistula puncture-related pain in
      hemodialysis patients.
AB  - Pain during areteriovenous fistula (AVF) cannulation remains a common problem in
      hemodialysis (HD) patients. This study was undertaken to assess the effect of
      cryotherapy on pain due to arteriovenous fistula puncture in hemodialysis
      patients. A convenience sample of 60 patients (30 each in experimental and
      control groups) who were undergoing hemodialysis by using AVF, was assessed in a
      randomized control trial. Hemodialysis patients who met the inclusion criteria,
      were randomly assigned to experimental and control groups using a randomization
      table. Objective and subjective pain scoring was done on two consecutive days of
      HD treatment (with cryotherapy for the experimental and without cryotherapy for
      the control group). The tools used were a questionnaire examining demographic and
      clinical characteristics, an observation checklist for assessing objective pain
      behavior, and a numerical rating scale for subjective pain assessment.
      Descriptive statistics were used as deemed appropriate. Chi square, two-sample
      and paired t-tests, the Mann Whitney test, Wilcoxon's signed rank test, the
      Kruskal Wallis test, and Spearman's and Pearson's correlations were used for
      inferential statistics. We found that the objective and subjective pain scores
      were found to be significantly (P = 0.001) reduced within the experimental group
      with the application of cryotherapy. This study highlights the need for adopting
      alternative therapies such as cryotherapy for effective pain management in
      hospital settings.

PMID- 20142928
TI  - Pregnancy related acute kidney injury: A single center experience from the
      Kashmir Valley.
AB  - All patients admitted with pregnancy related acute renal failure (PRAKI) from
      June 2005 to May 2007 were studied with respect to etiology, clinical features,
      and outcome of PRAKI. Of 569 cases of acute kidney injury (AKI), 40 (7.02%) cases
      were related to gestational problems; the age of the patients ranged from 15 to
      45 years. Septic abortion was the most common cause of PRAKI, accounting for 20
      (50%) cases of which 15 (75%) cases occurred in the first and five (25%) in the
      second trimester. Other causes were antepartum hemorrhage: six cases (15%),
      toxemia of pregnancy: six cases (15%), acute gastroenteritis: three cases (7.5%),
      postpartum hemorrhage: two cases (5%), acute pyelonephritis: two cases (5%), and
      postpartum, acute kidney injury: one case (2.5%). Dialysis was needed in 60% of
      the cases and mortality was observed in 20% of the cases. PRAKI continues to be a
      major concern in our society, causing a high maternal mortality. Septic abortion
      which has virtually disappeared from developed countries, continues to be a major
      cause of PRAKI in our society. Hence, there is a need to halt the practice of
      illegal abortions and improve antenatal care.

PMID- 20142929
TI  - All that is swollen and red is not infection!
AB  - Unilateral upper limb extremity swelling and pain are common presentations in
      clinical practice whose differential diagnoses include cellulitis, abscess,
      lymphoedema, and venous thrombosis. We report here the case of a renal transplant
      recipient with an unusual cause of upper extremity swelling and pain. His
      condition of native radiocephalic, arteriovenous (AV), fistula-related, venous
      hypertension was misdiagnosed and managed as cellulitis. This case illustrates
      the importance of an index of suspicion and careful clinical examination for
      diagnosis and thus, avoid potentially dangerous and distressing symptoms. The
      patient improved with a surgical AV fistula ligation.

PMID- 20142930
TI  - Hemolytic uremic syndrome following Hemiscorpius lepturus (scorpion) sting.
AB  - Scorpion envenomations are a public health problem in many countries. Scorpions
      are second only to snakes in causing human fatalities from envenomation. Species
      of scorpions capable of inflicting fatal stings are living in North and South
      Africa, the Middle East, India, America, Trinidad, and Tobago. Hemiscorpius
      lepturus (from the Hemiscorpiidae family) is the most medically important
      scorpion in Iran which accounts for 92% of all hospitalized scorpion sting cases.
      The venom from H. lepturus is primarily a cytotoxic agent and has hemolytic,
      nephrotoxic, and to some extent, hepatotoxic activities. We found a combination
      of microangiopatic hemolytic anemia, thrombocytopenia, and acute renal failure in
      a seven year-old female child who was referred to us with a 12 h history of
      bloody urine following a H. lepturus sting. Her blood smear showed fragmented
      erythrocytes and burr cells, leading us to a diagnosis of hemolytic uremic
      syndrome (HUS). This report highlights the importance of acceptable prophylaxis
      and therapeutic protocols for HUS in these patients.

PMID- 20142931
TI  - Nephrotic range proteinuria in c-ANCA-positive crescentic glomerulonephritis with
      linear immune deposits.
AB  - The three broad groups of rapidly progressing glomerulonephritis are anti
      glomerular basement membrane (anti-GBM) disease, renal vasculitis characterized
      by antineutrophil cytoplasmic antibody positivity, and a heterogeneous group with
      granular immune deposits. Anti-GBM disease with cytoplasmic antineutrophilic
      antibodies (c-ANCA) positivity (type III disease) is not known to present with
      nephrotic syndrome. We report here a rare presentation of nephrotic syndrome in
      Type III disease. Larger studies are warranted to determine whether the amount
      and/or type of immune deposits decide the range of proteinuria. These studies are
      also required to elucidate the impact of immune complex deposition on renal
      disease in c-ANCA-positive glomerulonephritis and to outline its pathogenetic
      mechanism.

PMID- 20142932
TI  - Blood urea nitrogen/creatinine ratio in rhabdomyolysis.
AB  - Rhabdomyolysis, a potentially life-threatening syndrome, is not an uncommon
      condition with around 38,000 cases been reported in the USA in 2000. The risk of
      developing acute renal failure in the initial days of presentation can be as high
      as 40% and approximately 28-37% of patients require short-term hemodialysis. This
      report discusses a case of rhabdomyolysis after seizures in which blood urea
      nitrogen (BUN), creatinine, and BUN/creatinine levels were examined during the
      course of illness in the hospital. We found that the BUN/creatinine ratio is not
      a reliable indicator of renal function in rhabdomyolysis. Potassium levels can be
      a better marker for the early recognition of acute renal failure and an
      indication for prompt treatment with dialysis, which is crucial to prevent fatal
      complications.

PMID- 20142934
TI  - About the journal.

PMID- 20142935
TI  - Welcome note.

PMID- 20142933
TI  - Nephrotic syndrome: A twist in the tail.

PMID- 20142936
TI  - Perception of general dental practitioners toward periodontal treatment: A
      survey.
AB  - Periodontology is a fast evolving field where newer insights into existing
      concepts are changing the face of the traditional periodontal treatment. Constant
      research is taking place so as to develop a number of newer avenues in the
      treatment of the periodontal diseases. However, the protocol of management of
      periodontal diseases in the setup of general dental practice has undergone little
      change over the last decade. So, a survey was carried out among 100 general
      dental practitioners by means of a questionnaire to identify the current status
      of periodontal treatment in dental clinics, the protocol of maintenance therapy,
      and the general awareness of the dental profession toward periodontal care.

PMID- 20142937
TI  - Comparitive effects of tetracyclines and citric acid on dentin root surface of
      periodontally involved human teeth: A scanning electron microscope study.
AB  - Periodontal diseases produce physical and chemical alterations in the root
      cementum. Various topical applications as root conditioning agents have been
      recommended as an adjunct to mechanical root surface debridement to remove smear
      layer, endotoxins and to expose collagen fibers on dentin surface. The objectives
      were to compare dentin surface changes following applications of tetracyclines
      and citric acid to the instrumented root surface of periodontally involved human
      teeth under scanning electron microscope.The study group comprised of 80 dentin
      samples, which were prepared from periodontally-compromised teeth, planned for
      extraction. Diseased surfaces were root planed. The teeth were sectioned and
      solutions of tetracycline HCl, minocycline, doxycycline and citric acid were
      applied to the surfaces with cotton pellets for 5minutes.The root surface samples
      were then examined by scanning electron microscope.Removal of smear layer in all
      the four groups was near total except a few areas. All four groups showed slight
      difference in mean number of total dentinal tubules. Minocycline and doxycycline
      showed no significant difference. The proportion of patent dentinal tubules was
      (74%) in tetracycline HCl group compared to minocycline (48.3%), doxycycline
      42%), citric acid (52%), showing the differences statistically significant.
      Tetracycline group showed higher number of patent tubules when compared to
      minocycline, doxycycline and the difference was statistically significant.Results
      of this study suggest that tetracycline is the best current tetracycline form for
      root surface conditioning as measured by its ability to affect both dentin smear
      layer removal and tubule exposure.

PMID- 20142938
TI  - Comparative analysis of GCF beta-glucuronidase level in diabetic and nondiabetic
      patients with chronic periodontitis: A clinicobiochemical study.
AB  - Recent evidences prove that, release of potent lysosomal enzymes e.g. beta
      Glucuronidase by degranulation of polymorponuclear leukocytes in host gingiva may
      contribute significantly to tissue destruction and the pathogenesis of
      periodontal disease. The purpose of the present study was to compare and
      correlate GCF beta-Glucuronidase with periodontal status among diabetic and non
      diabetic patients with chronic periodontitis. A total number of 75 patients were
      equally divided into Group I (control group), Group II (non diabetic with chronic
      periodontitis) and Group III (diabetic with chronic periodontitis). Clinical
      parameters like Plaque index, Gingival index, Probing Pocket Depth and RBS were
      recorded. The beta-Glucuronidase level in GCF of all three groups was determined
      by spectrophotometric analysis. It was observed that the periodontitis patients
      irrespective of their diabetic status, showed increased periodontal destruction
      with elevated level of beta-Glucuronidase than the controls. Also, the diabetic
      patients showed increased severity of periodontal destruction and the elevated
      level of beta-Glucuronidase, thus indicating diabetics at a higher risk for
      progressive periodontal destruction.

PMID- 20142939
TI  - Use of fibrin glue in periodontal flap surgery.
AB  - In the changing era of perio surgeries one innovative remedy has ended the
      inconvenience of suturing and has allowed the clinician to meet growing
      expectations and demands of today's dental patient, and the remedy is fibrin
      glue. When periodontal plastic surgical procedures done or implants placed in
      esthetic zone, fibrin sealants may be variable alternative to closing flaps with
      sutures and with histologic benefits and has potential uses in field of medicine.
      Fibrin sealant is an excellent beginner in the era of sutureless periodontal flap
      surgery, and this article is a humble effort to prove it.

PMID- 20142940
TI  - Periodontal considerations for Glanzmann's thrombasthenic patient.
AB  - Glanzmann's thrombasthenia (GT) was reported and described as a bleeding
      diathesis seen in children and characterized by diminished clot retraction. The
      disorder is caused by a deficiency in the platelet membrane glycoprotein IIb-IIIa
      complex, with bleeding due to defective platelet hemostatic plug formation. The
      recurrent features of GT include purpura, epistaxis, gingival hemorrhage, and
      menorrhagia. GT being an autosomal recessive trait is reported to be especially
      prevalent in populations where intermarriage is common. Typically, the patients
      are diagnosed in infancy within the age of five. Though no differences appear to
      occur based on sex men more frequently present with gingival bleeding. We report
      the case of a female patient with GT who presented with the chief complaint of
      gingival bleeding. The patient was given periodontal treatment under platelet
      transfusion followed by proper oral hygiene instructions. The report discusses
      periodontal consideration for GT patients.

PMID- 20142941
TI  - Application of ultrasound in periodontics: Part I.
AB  - Ultrasonic is a branch of acoustics concerned with sound vibrations in frequency
      ranges above audible level. Ultrasound uses the transmission and reflection of
      acoustic energy. A pulse is propagated and its reflection is received, both by
      the transducer. For clinical purposes ultrasound is generated by transducers,
      which converts electrical energy into ultrasonic waves. This is usually achieved
      by magnetostriction or piezoelectricity. Primary effects of ultrasound are
      thermal, mechanical (cavitation and microstreaming), and chemical
      (sonochemicals). Knowledge of the basic and other secondary effects of ultrasound
      is essential for the development of techniques of application.

PMID- 20142942
TI  - Future impact of nanotechnology on medicine and dentistry.
AB  - The human characteristics of curiosity, wonder, and ingenuity are as old as
      mankind. People around the world have been harnessing their curiosity into
      inquiry and the process of scientific methodology. Recent years have witnessed an
      unprecedented growth in research in the area of nanoscience. There is increasing
      optimism that nanotechnology applied to medicine and dentistry will bring
      significant advances in the diagnosis, treatment, and prevention of disease.
      Growing interest in the future medical applications of nanotechnology is leading
      to the emergence of a new field called nanomedicine. Nanomedicine needs to
      overcome the challenges for its application, to improve the understanding of
      pathophysiologic basis of disease, bring more sophisticated diagnostic
      opportunities, and yield more effective therapies and preventive properties. When
      doctors gain access to medical robots, they will be able to quickly cure most
      known diseases that hobble and kill people today, to rapidly repair most physical
      injuries our bodies can suffer, and to vastly extend the human health span.
      Molecular technology is destined to become the core technology underlying all of
      21(st) century medicine and dentistry. In this article, we have made an attempt
      to have an early glimpse on future impact of nanotechnology in medicine and
      dentistry.

PMID- 20142943
TI  - Comparison of neutrophil functions in diabetic and healthy subjects with chronic
      generalized periodontitis.
AB  - BACKGROUND: Diabetes mellitus is a systemic condition that has long been
      associated with an increased risk and severity of periodontal disease.
      Polymorphonuclear leukocytes (PMNs) play a key role in the maintenance of
      gingival and periodontal health. Reduced PMN function has been found in patients
      with diabetes. AIM: The objective of this study was to evaluate PMN functions in
      15 diabetic patients with chronic generalized periodontitis. MATERIALS AND
      METHODS: Chemotaxis, superoxide production, phagocytosis and killing of
      Porphyromonas gingivalis by diabetic PMNs were evaluated relative to healthy and
      matched controls. RESULTS: These analyses revealed a significant (P < 0.01)
      depression in the number of diabetic PMNs migrating along an fMLP gradient. In
      addition, a significant (P < 0.01) enhancement of diabetic PMN superoxide
      production was observed. Phagocytosis (P < 0.05) and killing by diabetic PMN of
      P. gingivalis was also impaired significantly (P < 0.01).

PMID- 20142944
TI  - Lymphocyte subpopulation in healthy and diseased gingival tissue.
AB  - In this study, infiltrating lymphocytes subpopulation in gingival sections of
      healthy, inflamed, and periodontitis lesions was investigated. A set of cluster
      of differentiation (CD) antigen specific monoclonal/polyclonal antibodies to
      detect different cell types within the tissues was used. These included anti-CD3
      (pan T-cell), anti-CD45RO (memory T-cell), anti-CD20 (B-cell), and kappa light
      chain (plasma cells). Biopsies of gingival tissue were obtained from 17 patients
      who had clinically healthy gingiva, from 18 patients with gingivitis, and 17
      patients with periodontitis.A significantly greater proportion of T-cells (P <
      0.00) was observed in healthy gingival and gingivitis tissue samples compared to
      periodontitis tissue samples. In addition, a greater proportion of B-cells was
      observed in periodontitis lesions than in the gingival lesions (P < 0.00). The
      memory T-cells and the kappa light-chain plasma cells were present in both
      healthy and diseased tissues, suggestive of previous activation by periodontal
      pathogenic microorganisms.In conclusion, these differences in the relative
      proportions of B- and T-cells may reflect a difference in the immunopathology of
      periodontitis and gingivitis lesions.

PMID- 20142945
TI  - Double laterally rotated bilayer flap operation for treatment of gingival
      recession: A report of two cases.
AB  - Esthetic concerns of the patient have become an essential part of dentistry,
      especially Periodontics. Periodontal plastic surgery is a rapidly emerging field,
      which helps us to meet this criterion. Root coverage is being achieved by a
      variety of techniques namely pedicle grafts and free soft tissue grafts. This
      article highlights on 2 case reports in which a new pedicle graft technique has
      been used for root coverage.

PMID- 20142946
TI  - Application of ultrasound in periodontics: Part II.
AB  - Ultrasound offers great potential in development of a noninvasive periodontal
      assessment tool that would offer great yield real time information, regarding
      clinical features such as pocket depth, attachment level, tissue thickness,
      histological change, calculus, bone morphology, as well as evaluation of tooth
      structure for fracture cracks. In therapeutics, ultrasonic instrumentation is
      proven effective and efficient in treating periodontal disease. When used
      properly, ultrasound-based instrument is kind to the soft tissues, require less
      healing time, and are less tiring for the operator. Microultrasonic instruments
      have been developed with the aim of improving root-surface debridement. The
      dye/paper method of mapping ultrasound fields demonstrated cavitational activity
      in an ultrasonic cleaning bath. Piezosurgery resulted in more favorable osseous
      repair and remodeling in comparison with carbide and diamond burs. The effect of
      ultrasound is not limited to fracture healing, but that bone healing after
      osteotomy or osteodistraction could be stimulated as well.

PMID- 20142947
TI  - Evidence-based periodontal therapy: An overview.
AB  - Dentists need to make clinical decisions based on limited scientific evidence. In
      clinical practice, a clinician must weigh a myriad of evidences every day. The
      goal of evidence-based dentistry is to help practitioners provide their patients
      with optimal care. This is achieved by integrating sound research evidence with
      personal clinical expertise and patient values to determine the best course of
      treatment. Periodontology has a rich background of research and scholarship.
      Therefore, efficient use of this wealth of research data needs to be a part of
      periodontal practice. Evidence-based periodontology aims to facilitate such an
      approach and it offers a bridge from science to clinical practice. The clinician
      must integrate the evidence with patient preference, scientific knowledge, and
      personal experience. Most important, it allows us to care for our patients.
      Therefore, evidence-based periodontology is a tool to support decision-making and
      integrating the best evidence available with clinical practice.

PMID- 20142948
TI  - Isolation of Helicobacter pylori from dental plaque: A microbiological study.
AB  - AIM: The aim of our study was to isolate H. pylori from dental plaque in gastric
      and duodenal ulcer patients and compare it with dental plaque of healthy
      subjects. MATERIALS AND METHODS: Fifty patients in the age range of 25-50 years
      who were endoscopically proven cases of duodenal and gastric ulcer were chosen.
      H. pylorus was isolated from the dental plaque of these patients using culture
      method and rapid urease test (RUT). It was compared with the dental plaque from
      control group (25 students). The specificity and sensitivity of RUT was compared
      with culture method. The oral hygiene index (OHI) score and plaque index were
      assessed. RESULTS: Ten percent positivity was observed in the study group by
      culture. Though RUT showed 70% positive isolation it is neither a specific test
      nor a conclusive test as compared to culture. The result correlates with oral
      hygiene in study population. CONCLUSION: Further, more studies are needed to
      compare RUT and culture, with serology and polymerase chain reactions. The
      ability to detect H. pylori from dental plaque using these methods offer the
      potential for the noninvasive test for infection and would aid in support of oral
      transmission of H. pylori.

PMID- 20142949
TI  - Clinical and histological evaluation of alloderm GBR and BioOss in the treatment
      of Siebert's class I ridge deficiency.
AB  - Complete prosthetic rehabilitation using implants require the presence of
      adequate dimensions of alveolar bone. Ridge augmentation procedures include the
      use of guided bone regeneration (GBR) procedures where the barrier membrane
      provides cell occlusion and space for the regenerating tissues. Alloderm GBR has
      been introduced for the purpose of augmenting bone and has been postulated to
      have the additionally ability to integrate into soft tissues. Twenty-two patients
      with Siebert's class I ridge deficiency were treated with BioOss and Alloderm GBR
      and followed up for a period of nine months. Significant increase in ridge
      dimensions of both hard and soft tissues were observed at six months period
      itself, suggesting that it as an effective method of augmenting deficient ridges.

PMID- 20142950
TI  - The challenge of antioxidants to free radicals in periodontitis.
AB  - Periodontal disease is a chronic adult condition. Bacteria implicated in the
      etiology of this disease causes destruction of connective tissue and bone. As a
      result of stimulation by bacterial antigen PMN produces free radicals via
      respiratory burst as a part of host response to infection. Patients with
      periodontal disease display increased PMN number and activity. This proliferation
      results in high degree of free radical release culminating in heightened
      oxidative damage to gingival tissues, periodontal ligament and alveolar bone.
      Damage mediated by free radicals can be mitigated by "ANTIOXIDANT DEFENSE SYSTEM
      ". Physiological alteration and pathological states produced by free radicals
      depend on disequilibrium between free radical production and antioxidant levels
      leading to oxidative stress.Hence this study has been designed to estimate the
      TOTAL ANTIOXIDANT CAPACITY in patients with PERIODONTITIS and healthy control
      subjects.

PMID- 20142951
TI  - Celebrating the past and looking ahead.

PMID- 20142952
TI  - Microbial keratitis in kingdom of bahrain: clinical and microbiology study.
AB  - BACKGROUND: Microbial keratitis is a potentially vision threatening condition
      worldwide. Knowing the predisposing factors and etiologic microorganism can help
      control and prevent this problem. This is the first study of its kind in Kingdom
      of Bahrain. OBJECTIVE: To study the profile of microbial keratitis in Bahrain
      with special focus on risk factors, clinical outcome and microbilogical results.
      METHODS: A retrospective analysis of all patients admitted in Salmaniya Medical
      Complex over a period of three years from January 2005 to January 2007 was
      performed. A total of 285 patients with keratitis were analysed. Non infectious
      corneal ulceration were excluded. Data collected from medical records were
      demographic features, predisposing factors, history of corneal trauma, associated
      ocular conditions, visual acuity at the time of presentation and the clinical
      course. Predisposing risk factors measured were contact lens use, presence of
      blepharitis, diabetes, lid abnormalities, dry eyes, keratoplasty and refractive
      surgery. For contact lens wearers any contact lens related risk factors that can
      lead to keratitis were measured. Pearson's chi-square test was used to carry out
      statistical analysis wherever required. RESULTS: Contact lens wear, as a risk
      factor for microbial keratitis, formed 40% of the total study population. Other
      risk factors identified were dry eyes 24 cases (8%), 10 blepharitis (3%), 22
      trauma (8%), abnormal lid position 14 cases (5%). 6 patients keratitis in a graft
      (2%), 3 had refractive surgery (1%). The most common causative organism isolated
      was pseudomonas aeroginosa (54%) followed by streptococcus 12%, staph 10%, other
      organisms 6%. 95% of contact lens wearers had pseudomonas Aeroginosa. This was
      statistically significant (p< 0.0001). The vast majority, 92% healed with
      scarring. 1% needed therapeutic keratoplasty and 7% lost to follow up. Risk
      factors in contact lens wearers were; 41 patients (36%) slept with the contact
      lenses. 12 (8%) had contact lens related trauma and 8 (7%) had poor hygiene.
      Sleeping with the contact lenses was statistically significant (p< 0.0001).
      CONCLUSION #ENTITYSTARTX00026; RECOMMENDATION: Contact lens wear is the major
      risk factor for microbial keratitis in Bahrain. Pseudomonas aeroginosa was the
      commonest bacteria isolated. Sleeping with the contact lenses is the major risk
      factor among contact lens wearers. Majority of keratitis patients resulted in
      permanent scarring on the cornea. Educating the public, especially on contact
      lens care and precaution, can help reduce this visual morbidity.

PMID- 20142953
TI  - Subjective and quantitative measurement of wavefront aberrations in nuclear
      cataracts - a retrospective case controlled study.
AB  - PURPOSE: To measure, quantify and compare Ocular Aberrations due to nuclear
      cataracts. SETTING: Department of ophthalmology and school for ophthalmic
      technicians, college of medicine and health sciences, Sultan Qaboos University,
      Muscat, Oman. DESIGN: Retrospective case controlled study. METHODS: 113 eyes of
      77 patients with nuclear cataract (NC) were recruited from outpatient clinic of a
      major tertiary referral center for Ophthalmology. Patients having NC with no co
      existing ocular pathologies were selected. All patients were subjected to
      wavefront aberrometry (make) using Hartmann-Shack (HS) aberrometer. Consents were
      taken from all patients. Higher order Aberrations (HOA) were calculated with
      Zernike polynomials up to the fourth order. For comparison 28 eyes of 15 subjects
      with no lenticular opacities (control group) were recruited and evaluated in an
      identical manner. No pupillary mydriasis was done in both groups. RESULTS: Total
      aberrations were almost six times higher in NC group compared to control (normal)
      subjects. The HOA were 21 times higher in NC group, and coma was significantly
      higher in NC eyes compared to normal (control) group. The pupillary diameter was
      significantly larger in control group (5.48mm +/- 1.0024, p<.001) compared to NC
      (3.05mm +/- 1.9145) subjects (probably due to younger control age group). Amongst
      Zernike coefficients up to fourth order, two polynomials, defocus (Z(2) (0)) and
      spherical aberration (Z(4) (2)) were found to be significantly greater amongst NC
      group, compared to normal control group. CONCLUSION: Nuclear cataracts
      predominantly produce increased defocus and spherical aberrations. This could
      explain visual symptoms like image deterioration in spite of normal Visual
      acuity.

PMID- 20142954
TI  - Neovascular glaucoma at king khaled eye specialist hospital - etiologic
      considerations.
AB  - BACKGROUND: Neovascular glaucoma (NVG) is a severe form of secondary glaucoma
      caused by the growth of new vessels over the trabecular meshwork. The principal
      causes are associated with retinal ischemia. Ablative treatment of the retina can
      prevent, halt, and even reverse the growth of new vessels on the iris and angle.
      It is an essential part of the management in most cases. AIMS: To determine the
      causes of NVG among Saudi patients, presented at the King Khaled Eye Specialist
      Hospital. METHODS: A retrospective review of 337 Saudi patients with NVG was
      obtained. All cases were reviewed for the evidence and causes of the disease, and
      their basic demographic information. A subset of 100 diabetic patients with PDR
      was further studied in greater detail for clinical findings and treatment
      history. RESULTS: The most common primary etiologic associations for NVG included
      diabetic retinopathy (DR) (56.06%), retinal venous obstruction (26.40%), and
      chronic retinal detachment (03.56%). A history of diabetes mellitus was reported
      in 65.04%, systemic arterial hypertension was noted in 61.00%, and evidence of
      renal impairment was documented in 22.00%. Vision was markedly reduced in most
      eyes with NVG (median: hand motion). The median best visual acuity in the fellow
      eye was 20/160. Among the 100 cases, with DR as a cause of NVG, 43 patients had
      bilateral neovascularization of the iris (NVI) and 72 had bilateral PDR. Sixty
      one patients had no previous laser treatment before the diagnosis of NVG. Among
      these, who received treatment, the median number of total laser spots was 1,003.
      CONCLUSIONS: Diabetes is a major cause of NVG presented to this tertiary eye care
      center in the Kingdom of Saudi Arabia followed by retinal venous obstruction.
      Close monitoring and full pan-retinal photocoagulation (PRP) were absent in most
      of the diabetic cases. It is important to recognize that the "unaffected" fellow
      eye, particularly in diabetic patients, may require fairly urgent treatment as
      well.

PMID- 20142956
TI  - Non-traumatic Ocular Findings in Industrial Technical Workers in Delta State,
      Nigeria.
AB  - PURPOSE: To determine the pattern of non-traumatic ocular disorders in industrial
      technical workers in the Delta state, Nigeria. METHODS: A cross-sectional study
      of the pattern of non-traumatic ocular disorders among industrial technical
      workers in 3 factories in Ughelli North local Government Area of Delta state,
      Nigeria was conducted between February, 2002 and May, 2002. In addition to the
      demographic, the workers were studied for the presence of any non-trauma related
      ocular findings. Visual acuity of these workers was obtained as well as ocular
      examination was performed by using the Snellen's chart, pen torch,
      ophthalmoscope, Perkins hand-held tonometer, Ishihara plates. Patients were
      refracted if their visual acuity was less than normal. RESULTS: Five hundred
      technical workers were screened that included 200 (40%) from the construction
      industry, 180 (36%) from the rubber factory and 120(24%) from the oil mill. All
      the workers studied were males. Ocular disorders were seen in 664 (66.4%) of the
      eyes. The most common ocular disorders were pingueculum 215 (21.5%), presbyopia
      97 (9.7%), refractive error 94 (9.4%), pterygium 86 (8.6%) and chronic
      conjunctivitis 45 (4.5%). None of the workers was blind from non-traumatic
      causes. Only 36 (7.2%) workers wore any protective eye devices at work.
      CONCLUSION: Non-traumatic ocular disorders are common in the industrialized
      technical workers in the Delta state of Nigeria. The use of protective eye
      devices is low in these workers and suggests that measures to implement ocular
      safety should be undertaken in these industries.

PMID- 20142955
TI  - Bleb-related Endophthalmitis: Clinical Presentation, Isolates, Treatment and
      Visual Outcome of Culture-proven Cases.
AB  - PURPOSE: To investigate clinical features, causative organisms and their
      antibiotic sensitivity, management, and visual acuity outcomes of eyes with bleb
      related endophthalmitis (BRE). DESIGN: Retrospective, noncomparative, consecutive
      eye series. METHODS: Clinical and microbiological records of patients with
      culture positive bleb-related endophthalmitis treated at a single institution
      between April 1995 and February 2002 were revised retrospectively. MAIN OUTCOME
      MEASURES: Final visual acuity, loss of eye and complications. RESULTS: There were
      34 cases with presenting visual acuities ranging from 20/200 to light perception.
      Decrease of visual acuity was the most frequent sign (94%) followed by pain (79%)
      and hypopyon (53%). Associated features included pseudophakia (79%), vitreous
      wick (29%), and wound leak (12%). The most frequent organisms isolated from
      vitreous specimens, were streptococcus species (55%) and gram positive coagulase
      negative staphylococci (20%). Polymicrobial growth was noted in 27% of cases. The
      cultured organisms were sensitive to antibiotics used in 94% of cases. Treatment
      modality used was vitreous tap with antibiotic injection without (65%) or with
      vitrectomy (35%). The most common intravitreal antibiotics combination was
      vancomycin with ceftazidime, Intravitreal dexamethsone was administered in 56% of
      cases. Final visual outcome of 20/400 or better was noticed in 50% of cases
      without and 33% with vitrectomy, but this was not statistically significant
      (p=0.45). The difference in final visual acuity of cases infected by gram
      positive coagulase-negative staphylococci and streptococcus species were not
      statistically significant (p= 0.18). Overall, final visual outcome of 20/400 or
      better was noticed in 47% of cases, while no light perception was recorded in 8
      (24%) cases. Of no light perception cases 7 underwent evisceration or
      enucleation. Overall, 32% of the cases experienced other complications like
      retinal detachment with dislocated intraocular lens, phthisis bulbi, and
      epiretinal membrane formation. CONCLUSION: BRE is associated with substantial
      visual morbidity. Prompt treatment of BRE with intravitreal vancomycin and broad
      spectrum antibiotics recommended while culture results are pending. Neither tap
      injection with vitrectomy nor tap-injection without vitrectomy proved superior in
      the management of this condition.

PMID- 20142957
TI  - Low vision AIDS provision for visually impaired egyptian patients - a clinical
      outcome.
AB  - PURPOSE: To evaluate a low vision rehabilitation service implemented for
      heterogeneously diverse group of Egyptianpatients with vision loss in terms of
      improving their visual performance and fulfilling their visual needs. METHODS:
      Fifty patients with low vision were included in a prospective study. History
      taking, ophthalmic examinationand evaluation of the visual functions were
      performed for all patients. The required magnification was calculated,
      andsubsequently a low vision aid was chosen after counseling with patients. Low
      vision aids were tried in office, followedby a period of training before patients
      received their own low vision aids. Follow up was done for 6 months. RESULTS: All
      patients who were referred to the low vision unit were not satisfied with their
      current spectacles or lowvision aids. After training and prescription of suitable
      LVAs, the improvement in distance and near visual acuity wasstatistically
      significant (p<0.001). Fifty-six per cent of the patients (n=28) showed
      improvement in distance visualacuity of 5 lines or more, and 57% of the patients
      (n=27) could discern N8 print size or better. The most commonlyused aids were
      high powered near adds. Despite the complaints about the appearance and use of
      LVAs, 76% of thepatients reported being moderately to highly-satisfied with their
      aids. CONCLUSIONS: The significant improvement in the visual performance of
      patients with low vision after the prescriptionand training on the use of LVAs,
      associated with patients' satisfaction, confirms the importance of expanding
      lowvision rehabilitative services and increasing the public awareness of its
      existence and benefits.

PMID- 20142959
TI  - Neuro-ophthalmic Afferent System Diagnoses A General Ophthalmologist Should
      (Almost) Never Make Alone.
AB  - The general ophthalmologist might be called upon to make the diagnosis of neuro
      ophthlamic conditions which are either rare or require extensive testing to
      exclude alternative diagnoses. This paper reviews some common afferent system
      neuro-ophthlamologic diagnoses that the general ophthalmologist should rarely if
      ever make alone. These include posterior ischemic optic neuropathy, chronic optic
      neuritis, retinal migraine, and optic atrophy. Although these diagnoses do exist
      they are typically diagnoses of exclusion that require neuroimaging and ancillary
      testing and have no diagnostic test to confirm the diagnosis.

PMID- 20142958
TI  - Directed Therapy: An Approach to the Improved Treatment of Exfoliation syndrome.
AB  - Exfoliation syndrome (XFS) is an age-related, generalized disorder of the
      extracellular matrix characterized by the production and progressive accumulation
      of a fibrillar extracellular material in many ocular tissues and is the most
      common identifiable cause of open-angle glaucoma worldwide. Exfoliation syndrome
      plays an etiologic role in open-angle glaucoma, angle-closure glaucoma, cataract,
      and retinal vein occlusion. It is accompanied by an increase in serious
      complications at the time of cataract extraction, such as zonular dialysis,
      capsular rupture, and vitreous loss. It is associated systemically with an
      increasing number of vascular disorders, hearing loss, and Alzheimer's disease.
      Exfoliation syndrome appears to be a disease of elastic tissue microfibrils.
      Directed therapy simply means devising specific treatments for specific diseases.
      There was little incentive to attempt to distinguish between various open-angle
      glaucomas if the treatments were essentially the same. However, this view also
      prevented the application of directed therapy in those instances in which such
      was available and applicable. Pilocarpine has multiple beneficial actions in eyes
      with XFS. Not only does it lower IOP, but by increasing aqueous outflow, it
      should enable the trabecular meshwork to clear more rapidly, and by limiting
      pupillary movement, should slow the progression of the disease. Theoretically,
      miotics should be the first line of treatment. Pilocarpine 2% q.h.s. can provide
      sufficient limitation of pupillary mobility without causing these side effects.
      In 2007, two common single nucleotide polymorphisms in the coding region of the
      lysyl oxidase-like 1 (LOXL1) gene located on chromosome 15 were specifically
      associated with XFS and XFG. LOXL1 is a member of the lysyl oxidase family of
      enzymes, which are essential for the formation, stabilization, maintenance, and
      remodelling of elastic fibers and prevent age-related loss of elasticity of
      tissues. LOXL1 protein is a major component of exfoliation deposits and appears
      to play a role in its accumulation and in concomitant elastotic processes in
      intra- and extraocular tissues of XFS patients. This discovery should open the
      way to new approaches and directions of therapy for this protean disorder.

PMID- 20142961
TI  - The Importance of Structured Scientific Enquiry: A priority for the MEAJO
      Editorial Board.

PMID- 20142960
TI  - The SCHWIND AMARIS Total-Tech Laser as An All-Rounder in Refractive Surgery.
AB  - PURPOSE: To describe and argument an overview of the main features and unique
      technical points of AMARIS Total-Tech Laser, coupled with patient outcomes
      supporting the decision to perform LASIK treatments with maximised outcomes.
      SETTINGS: Dr. M.C. Arbelaez, Muscat Eye Laser Center, Muscat, Sultanate of Oman.
      METHODS: The findings collected during 18-month experience using SCHWIND AMARIS
      Total-Tech Laser have been reviewed to provide arguments for supporting the
      decision to perform LASIK treatments with maximised outcomes. For updated
      clinical outcomes, the last 100 myopic astigmatism treatments, the last 100
      hyperopic astigmatism treatments, the last 30 ocular-wavefront-guided treatments,
      and the last 30 corneal-wavefront-guided treatments, all with 6-month follow-up,
      were included. For all those, LDV femtosecond system was used to prepare the
      flaps, and AMARIS flying spot system was used to perform ablations. Clinical
      outcomes were evaluated in terms of predictability, refractive outcome, safety,
      wavefront aberration, and contrast sensitivity. RESULTS: 6-month postoperatively,
      mean defocus was -0.14+/-0.31D and astigmatism 0.25+/-0.37D. 70+/- eyes were
      within +/-0.25D of emmetropia. 43+/- eyes gained lines of best spectacle
      corrected visual acuity. For Aberration-Free treatments, none of the aberration
      metrics changed from pre- to postoperative values in a clinically relevant
      amount. For ocular-wavefront-guided treatments, the surgery did not change coma
      or spherical aberration, and reduced trefoil (p<0.005). For corneal-wavefront
      guided treatments, the trefoil, coma, and spherical aberrations, as well as the
      total root-mean-square values of higher order aberration, were significantly
      reduced (p<.05) when the pre-existing aberrations were greater than the
      repeatability and the biological noise. CONCLUSIONS: Although this review does
      not allow for evidence-based conclusions, following our strategy, LASIK results
      were excellent. LASIK surgery with AMARIS system yield excellent outcomes.
      Refractions were reduced to subclinical values with no induction of High-Order
      Aberrations. Neither adverse events nor complications were observed.

PMID- 20142963
TI  - Assessment and management of children with visual impairment.
AB  - PURPOSE: The aim of this work was to evaluate the role of low vision aids in
      improving visual performance and response in children with low vision. STUDY
      DESIGN: Prospective clinical case series. MATERIALS AND METHODS: This study was
      conducted on 50 patients that met the international criteria for a diagnosis of
      low vision. Their ages ranged from 5 to 15 years. Assessment of low vision
      included distance and near visual acuity assessment, color vision and contrast
      sensitivity function. Low vision aids were prescribed based on initial evaluation
      and the patient's visual needs. Patients were followed up for 1 year using the
      tests done at the initial examination and a visual function assessment
      questionnaire. RESULTS: The duration of visual impairment ranged from 1 to 10
      years, with mean duration +/- SD being 4.6+/- 2.3299. The near visual acuities
      ranged from A10 to A20, with mean near acuity +/- SD being A13.632 +/- 3.17171.
      Far visual acuities ranged from 6/60 (0.06) to 6/24 (0.25), with mean far visual
      acuity +/- SD being 0.122 +/- 0.1191. All patients had impaired contrast
      sensitivity function as tested using the vision contrast testing system (VCTS)
      chart for all spatial frequencies. Distance and near vision aids were prescribed
      according to the visual acuity and the visual needs of every patient. All
      patients in the age group 5-7 years could be integrated in mainstream schools.
      The remaining patients that were already integrated in schools demonstrated
      greater independency regarding reading books and copying from blackboards.
      CONCLUSION: Our study confirmed that low vision aids could play an effective role
      in minimizing the impact of low vision and improving the visual performance of
      children with low vision, leading to maximizing their social and educational
      integration.

PMID- 20142962
TI  - Carotid cavernous fistula: ophthalmological implications.
AB  - Carotid cavernous fistula (CCF) is an abnormal communication between the
      cavernous sinus and the carotid arterial system. A CCF can be due to a direct
      connection between the cavernous segment of the internal carotid artery and the
      cavernous sinus, or a communication between the cavernous sinus, and one or more
      meningeal branches of the internal carotid artery, external carotid artery or
      both. These fistulas may be divided into spontaneous or traumatic in relation to
      cause and direct or dural in relation to angiographic findings. The dural
      fistulas usually have low rates of arterial blood flow and may be difficult to
      diagnose without angiography. Patients with CCF may initially present to an
      ophthalmologist with decreased vision, conjunctival chemosis, external
      ophthalmoplegia and proptosis. Patients with CCF may have predisposing causes,
      which need to be elicited. Radiological features may be helpful in confirming the
      diagnosis and determining possible intervention. Patients with any associated
      visual impairment or ocular conditions, such as glaucoma, need to be identified
      and treated. Based on patient's signs and symptoms, timely intervention is
      mandatory to prevent morbidity or mortality. The conventional treatments include
      carotid ligation and embolization, with minimal significant morbidity or
      mortality. Ophthalmologist may be the first physician to encounter a patient with
      clinical manifestations of CCF, and this review article should help in
      understanding the clinical features of CCF, current diagnostic approach,
      usefulness of the available imaging modalities, possible modes of treatment and
      expected outcome.

PMID- 20142964
TI  - Prevalence of uncorrected refractive error and other eye problems among urban and
      rural school children.
AB  - BACKGROUND: Uncorrected refractive error is an avoidable cause of visual
      impairment. AIM: To compare the magnitude and determinants of uncorrected
      refractive error, such as age, sex, family history of refractive error and use of
      spectacles among school children 6-15 years old in urban and rural Maharashtra,
      India. STUDY DESIGN: This was a review of school-based vision screening conducted
      in 2004-2005. MATERIALS AND METHODS: Optometrists assessed visual acuity,
      amblyopia and strabismus in rural children. Teachers assessed visual acuity and
      then optometrists confirmed their findings in urban schools. Ophthalmologists
      screened for ocular pathology. Data of uncorrected refractive error, amblyopia,
      strabismus and blinding eye diseases was analyzed to compare the prevalence and
      risk factors among children of rural and urban areas. RESULTS: We examined 5,021
      children of 8 urban clusters and 7,401 children of 28 rural clusters. The cluster
      weighted prevalence of uncorrected refractive error in urban and rural children
      was 5.46% (95% CI, 5.44-5.48) and 2.63% (95% CI, 2.62-2.64), respectively. The
      prevalence of myopia, hypermetropia and astigmatism in urban children was 3.16%,
      1.06% and 0.16%, respectively. In rural children, the prevalence of myopia,
      hypermetropia and astigmatism was 1.45%, 0.39% and 0.21%, respectively. The
      prevalence of amblyopia was 0.8% in urban and 0.2% in rural children. Thirteen to
      15 years old children attending urban schools were most likely to have
      uncorrected myopia. CONCLUSION: The prevalence of uncorrected refractive error,
      especially myopia, was higher in urban children. Causes of higher prevalence and
      barriers to refractive error correction services should be identified and
      addressed. Eye screening of school children is recommended. However, the approach
      used may be different for urban and rural school children.

PMID- 20142965
TI  - Intravitreal bevacizumab (avastin) as an adjuvant treatment in cases of
      neovascular glaucoma.
AB  - PURPOSE: To evaluate the effect of intravitreal bevacizumab (avastin) injection
      in cases of neovascular glaucoma. STUDY DESIGN: Clinical case series. MATERIALS
      AND METHODS: Sixteen eyes of 16 patients with rubeosis iridis and secondary
      glaucoma were administered intravitreal injection of bevacizumab (2.5 mg). The
      patients were followed for 2 months. RESULTS: We noted partial or complete
      regression of iris neovascularization 1 week after injection of bevacizumab.
      Reproliferation of new vessels was detected in 25% of the cases after 2 months.
      The mean intraocular pressure (IOP) before injection was 28+/- 9.3 mm Hg under
      topical ss-blocker and systemic acetazolamide. One week after injection, the IOP
      decreased to 21.7+/- 11.5 mm Hg (5 cases without anti-glaucoma drugs, 6 cases
      with topical ss-blocker and 5 cases with both topical ss-blocker and systemic
      acetazolamide). CONCLUSION: Intravitreal bevacizumab (avastin) injection leads to
      regression of iris neovascularization with subsequent drop of IOP in eyes with
      neovascular glaucoma.

PMID- 20142966
TI  - Presenting visual acuities in a referral eye center in an oil-producing area of
      Nigeria.
AB  - OBJECTIVES: To determine the pattern of presenting visual acuities at an eye
      center in the Niger Delta region of Nigeria. STUDY DESIGN: Retrospective chart
      review METHODS: A retrospective review of patient records attending a private
      referral eye center providing services for company patients and the general
      public in the region. Information was obtained from computerized medical records
      of 6533 patients who attended the center for various eye concerns in a 5-year
      period (January 1998 to December 2002). RESULTS: A total of 6533 patients were
      seen in this 5-year period of which 2472 (37.8%) were company patients and 4061
      (62.2%). were private patients. There were 3879 males (59.4%) and 2654 females
      (40.6%). A visual acuity of 6/6 or better was seen in 50.8% of the patients. In
      76.6% of patients, a visual acuity of 6/18 or better was recorded. There were
      21.4% of patients in the low vision group. Bilateral blindness occurred in 2.1%
      of patients. Monocular blindness occurred in 3.7% of patients. Low vision
      occurred in 16.9% of company patients and 24.1% of private patients. Bilateral
      blindness occurred in 0.9% of company patients and 2.7% of private patients,
      while monocular blindness occurred in 1.2% of company patients and 5.2% of
      private patients. The main ocular problems were refractive error, glaucoma,
      conjunctivitis, headaches, ocular trauma, retina and related pathologies,
      cataract, uveitis, pterygium and corneal problems. CONCLUSION: The incidence of
      low vision and blindness is high in the oil-producing area of the Niger Delta
      region of Nigeria. Low vision and blindness were more common in private patients
      than in company patients.

PMID- 20142967
TI  - Prevalence of punctal stenosis among ophthalmology patients.
AB  - PURPOSE: To estimate the prevalence of punctal stenosis among patients visiting
      the general ophthalmology clinic for routine checkup. DESIGN: Prospective,
      observational case series. MATERIALS AND METHODS: A total of 682 patients were
      evaluated for evidence of punctal stenosis from May to November 2008. Any
      associated findings from clinical examination were recorded. RESULTS: As many as
      54.3% (370/682) of the candidates had punctal stenosis. The prevalence is
      associated significantly with increasing age (p=.001), and no gender predilection
      was found. It was due to chronic blepharitis in 97% (359/370), entropion in 1.4%
      (5/370) and unknown causes in 1.6% (6/370) of the patients. As many as 58.1%
      (215/370) did not have subjective or objective evidence of epiphora, and all of
      them had a tear film breakup time of less than 10 seconds and positive corneal
      fluorescein staining. CONCLUSION: Punctal stenosis is a common finding among
      patients presenting for routine eye checkup. It increases with advancing age, and
      the most common predisposing factor is chronic blepharitis. A significant number
      of patients can be asymptomatic as they have concurrent dry eye disease. Surgical
      intervention is not recommended unless the patient is symptomatic after treating
      any associated blepharitis and dry eye disease.

PMID- 20142968
TI  - Cataract surgical outcomes in diabetic patients: case control study.
AB  - PURPOSE: To determine the visual outcome of cataract surgery in diabetes mellitus
      with advanced cataract in a tertiary institution in Nigeria. DESIGN: A
      retrospective case control study conducted at the University College Hospital,
      Ibadan Nigeria. SUBJECTS: Twenty three consecutive patients with diabetes and 23
      age and sex matched non-diabetic control patients who had extracapsular cataract
      extraction for advanced cataract between 2002-2005. MAIN OUTCOME: Mean post
      operative visual acuity and surgical complications. RESULTS: Twenty three
      patients with diabetes mellitus and 23 non diabetic controls were studied; mean
      duration of diabetes was 8.1 +/- 7.2 years. The mean post operative visual acuity
      in diabetics was 0.11+/-0.38, 0.33+/-0.57 and 0.38+/-0.49 at one week, two months
      and six months compared with 0.23+/-0.19, 0.46+/-0.37 and 0.48+/-0.31 in non
      diabetics. (p=0.207, 0.403 and 0.465 respectively). Improvement in preoperative
      visual acuity was noted in 84.2% and 90% in diabetics and non-diabetics
      respectively. Poor visual outcome in diabetics was mainly due to diabetic
      retinopathy, maculopathy or diabetes related surgical complications. CONCLUSION:
      Visual improvement was seen following surgery for advanced cataract in diabetics
      in this study population. Post operative monitoring for treatment of diabetic
      retinopathy may enhance visual outcome.

PMID- 20142969
TI  - Traditional medicine in oman: its role in ophthalmology.
AB  - AIM: To present three patients with ocular disease who developed a range of
      complications following use of traditional medications. SETTINGS AND DESIGN: Case
      series METHODS: Three patients who were examined in the Ophthalmic department of
      a tertiary care teaching hospital in the Sultanate of Oman between 2003 and 2004,
      seeking care following use of traditional medicines and or healing practices for
      various ophthalmic problems described below. RESULTS: The first patient was a
      computer professional with a chalazion; the patient used a plant extract from
      'Calotropis procera' as a part of the treatment. He developed corneal edema with
      decrease in vision in his left eye following application of the plant extract.
      Treatment with topical steroids and antibiotics resulted in a complete clinical
      and visual recovery. The second patient developed a fungal corneal ulcer
      (dermatophyte - Trichophyton mentagrophyte) after sustaining injury with an
      animal tail to the right eye and used honey for pain relief prior to
      presentation. She responded poorly to anti-fungal treatment, underwent a
      penetrating keratoplasty with recurrence of infection in the graft that resulted
      in a vascularized corneal scar. The third patient was a five-year-old child who
      was treated with 'wasam' on the occiput for intraocular inflammation following
      bilateral uncomplicated cataract extraction. Following this treatment the topical
      steroid was discontinued. The 'Wasam' treatment indirectly resulted in
      exacerbation of the intraocular inflammation and secondary glaucoma and poor
      vision as well as 'Wasam ulcers' on the occiput. Despite treatment of the
      intraocular inflammation, the visual outcome was poor. CONCLUSION: Traditional
      medicine in Oman is sought by many for variable reasons. Lack of evidence-based
      scientific data on its safety or efficacy does not deter the Omanis from flocking
      the traditional healers. However, when applied in the treatment of ocular
      diseases, traditional medicine and healing practices seem to cause more harm than
      benefit for the patient.

PMID- 20142970
TI  - Late occurrence of lens particle glaucoma due to an occult glass intralenticular
      foreign body.
AB  - We report a case of traumatic mature cataract with a late occurrence of lens
      particle glaucoma after 11 years of trauma due to a presence of an occult
      intralenticular glass foreign body which was detected accidentally during the
      cataract surgery.

PMID- 20142971
TI  - Glaucoma surgery: how do we get from here to there?

PMID- 20142972
TI  - Results from the tube versus trabeculectomy study.
AB  - The Tube Versus Trabeculectomy (TVT) Study is a multicenter randomized clinical
      trial comparing the safety and efficacy of tube shunt surgery to trabeculectomy
      with mitomycin (MMC) in eyes with previous cataract and/or failed glaucoma
      surgery. Tube shunt surgery was more likely to maintain intraocular pressure
      (IOP) control and avoid persistent hypotony, reoperation for glaucoma, or loss of
      light perception vision than trabeculectomy with MMC during the first year of
      follow-up. Both surgical procedures had similar IOP reduction at 1 year, but less
      supplemental medical therapy was used following trabeculectomy. The incidence of
      postoperative complications was higher after trabeculectomy with MMC relative to
      tube shunt surgery, but serious complications associated with vision loss and/or
      reoperation developed with similar frequency after both of the procedures. There
      was no significant difference in the rate of vision loss following trabeculectomy
      with MMC and tube shunt surgery after 1 year of follow-up. Cataract progression
      was common, but occurred with similar frequency with both of the surgical
      procedures.

PMID- 20142973
TI  - The moorfields safer surgery system.
AB  - This review presents the 'Moorfields Safer Surgery System', which is designed to
      improve the consistency and outcomes of trabeculectomy surgery. Evidence-based
      recommendations are made for each step of the surgery. This system requires a
      minimum of equipment and can be easily implemented by most surgeons. The system
      is ultimately designed to preserve the vision in our patients by minimising
      complications while maintaining a desired intraocular pressure.

PMID- 20142974
TI  - Update on laser trabeculoplasty.
AB  - Newer techniques of Laser Trabeculoplasty have revived the procedure and gained
      widespread acceptance by the ophthalmic community. This review was undertaken to
      address the evolution of different laser trabeculoplaty techniques, proposed
      mechanisms of action as well as review current studies of the therapeutic effects
      of these interventions.

PMID- 20142975
TI  - Cataract surgery to lower intraocular pressure.
AB  - Cataract and glaucoma are common co morbidities. Cataract surgery is frequently
      performed in patients with glaucoma. In this study, a review of literature with
      search terms of cataract, glaucoma and intraocular pressure is followed by
      evaluation and synthesis of data to determine the effect of cataract surgery on
      intraocular pressure. Cataract surgery seems to lower intraocular pressure on a
      sustained basis, especially in patients with higher preoperative intraocular
      pressure. The mechanism of action of these finds remains speculative.

PMID- 20142976
TI  - Deep sclerectomy: safety and efficacy.
AB  - Deep Sclerectomy is a non penetrating surgical procedure for the treatment of
      open angle glaucoma. In this article we will describe the surgical technique, the
      indications for surgery and will review the scientific literature on surgical
      outcome following this procedure. We will also discuss the important role played
      by antimetabolites, implants and the use of gonipuncture to achieve the desired
      IOP reduction.

PMID- 20142977
TI  - Canaloplasty using iTrack 250 Microcatheter with Suture Tensioning on Schlemm's
      Canal.
AB  - Open angle glaucoma (OAG) necessitating surgery has traditionally been treated
      with filtering procedures using antifibrotics. Unfortunately, such filtering
      procedures are not without the risk of postsurgical complications. Increasing
      interest in blebless surgery has led to innovative surgical procedures aimed at
      rejuvenating the natural trabeculo canalicular outflow pathway. Circumferential
      catheterization with suture tensioning of Schlemm's canal has emerged as a safe
      and effective way to surgically treat OAG.

PMID- 20142978
TI  - Endocyclophotocoagulation.
AB  - Endocyclophotocoagulation is becoming a widely accepted and popular treatment of
      refractory glaucoma and as an adjunct to cataract surgery in both medically
      controlled and uncontrolled glaucoma. We present a brief review of the
      indications, technique, safety and efficacy of endoscopic photococylocoagulation.

PMID- 20142979
TI  - The ex-press mini glaucoma shunt: technique and experience.
AB  - The Ex-Press Mini Glaucoma Shunt has been available internationally for almost a
      decade with almost 35,000 implantations world wide. The device shunts aqueous
      from the anterior chamber to a subconjunctival reservoir in a similar fashion as
      trabeculectomy, without removal of any sclera or iris tissue. Developments in
      ophthalmic surgery have been focused on smaller incisions to improve patient
      outcomes and visual recovery. The Ex-Press is an example of these developments.
      This article will review the surgical technique for implanting the Ex-Press Mini
      Glaucoma Shunt and will highlight the clinical experience with the device.

PMID- 20142980
TI  - Glaukos iStent Trabecular Micro-Bypass.
AB  - The iStent trabecular micro-bypass system (Glaukos Corp. Laguna Hills, CA) was
      developed to address the limitations of current medical and surgical therapies
      for glaucoma treatment. The iStent((R)) is inserted ab interno through a small
      temporal clear corneal incision, bypassing the trabecular meshwork and placed in
      Schlemm's canal at the lower nasal quadrant. Implantation of this stent into
      Schlemm's canal allows aqueous humor to drain directly from the anterior chamber
      into Schlemm's canal bypassing the obstructed trabecular meshwork. For this
      review, a Medline search was performed using the terms "trabecular micro-bypass
      stent" and "trabecular bypass stent." The online abstract database for the
      American Academy of Ophthalmology was also reviewed. Abstracts which duplicated
      published articles were excluded. All relevant papers (n is equal to three) and
      abstracts (n is equal to one) were included in this review. Multiple, prospective
      multi-country, clinical trials have demonstrated the safety and efficacy of
      iStent in reducing IOP, when compared to traditional treatment modalities, while
      reducing/ eliminating the need for ocular antihypertensive drugs when implanted
      in OAG patients during combined cataract surgery or in patients with glaucoma
      refractory to traditional treatment modalities.

PMID- 20142981
TI  - Detection of early glaucomatous damage in pseudo exfoliation syndrome by
      assessment of retinal nerve fiber layer thickness.
AB  - PURPOSE: To detect early glaucomatous changes in pseudo exfoliative patients with
      normal intraocular pressure (IOP), visual field and optic nerve head appearance;
      by measuring retinal nerve fiber layer (RNFL) thickness using optical coherence
      tomography (OCT). DESIGN: A prospective observational case-control study.
      PARTICIPANTS: Twenty non-glaucomatous (normal IOP, fundus and visual field)
      pseudo exfoliative patients and 20 age matched healthy control subjects.
      MATERIALS AND METHODS: The RNFL thickness (global and four quadrants) was
      assessed using combined imaging system OTI (OCT/SLO) and compared with age
      matched normal control subjects. RESULTS: The RNFL in patients with pseudo
      exfoliation syndrome (PXS) was significantly thinner in all quadrants except the
      nasal quadrant compared to the control group (p less than 0.05). CONCLUSION:
      Measurement of RNFL thickness by OCT is useful in detecting early RNFL damage
      which in turn provides clinically relevant information in detecting early
      glaucomatous changes in pseudo exfoliative patients.

PMID- 20142982
TI  - Vascular risk factors for open angle glaucoma in african eyes.
AB  - CONTEXT: The exact patho physiological mechanizm of optic nerve damage in
      glaucoma is not fully understood. AIM: To assess the vascular risk factors in
      open angle glaucoma in African eyes. SETTINGS AND DESIGN: Prospective multicenter
      hospital-based study in Edo State, Nigeria. MATERIALS AND METHODS: Three hundred
      and twenty-two glaucoma patients and 184 control subjects were included in the
      study comprising 200 male glaucoma patients (62.11%) and 122 females (37.89%). A
      cohort of consecutive patients with a diagnosis of primary open angle glaucoma
      and age and sex matched control subjects were included in this prospective, cross
      sectional, and multicenter hospital-based study conducted during the period
      January-June 2008. Blood pressure (BP), pulse and intraocular pressure findings
      were recorded and mean BP, pulse and perfusion pressure for each eye calculated.
      STATISTICAL ANALYSIS USED: Mean, standard deviations, 95% confidence intervals,
      Welch's t test, and Fisher's exact test were calculated. RESULTS: The mean IOP in
      the 644 eyes of the 322 glaucoma patients was 22.65 mmHg (SD plus/minus 11.06).
      The systolic blood pressure (P < 0.0001), diastolic blood pressure (P < 0.0001),
      mean arterial blood pressure (P < 0.0001), pulse pressure (P < 0.01), systolic
      perfusion pressure (P < 0.01) were all significantly higher in glaucoma patients
      than in control. CONCLUSIONS: Higher systolic, diastolic, mean arterial BP and
      pulse pressure was found in Black African patients with open angle glaucoma.

PMID- 20142983
TI  - Ahmed glaucoma valve implant: experience in East Africa.
AB  - PURPOSE: To describe short term outcomes of Ahmed Glaucoma Valve [AGV]
      implantation in East African patients. MATERIALS AND METHODS: In this multi
      center retrospective case series we reviewed eyes of Black African patients with
      refractory glaucoma, treated consecutively with Ahmed Glaucoma Valve
      implantation, in two centers in Kenya between January 2006 and October 2007.
      RESULTS: About 25 cases including 18 [72%] pediatric eyes and seven [28%] adult
      eyes were identified. Results have been presented with a median follow-up of two
      months with inter-quartile range [IQR] of one to 12 months. intraocular pressure
      [IOP] was reduced from a mean of 36.4 mmHg preoperatively to 16.7 mmHg and
      glaucoma medications were lowered from a mean of 1.32 before surgery to 0.2 after
      surgery. The success rate during short term follow-up was 79%. The mean visual
      acuity dropped slightly from 6/18 pre-operatively to 6/24. There was only one
      major complication of an extruded, infected valve in a child. CONCLUSIONS: The
      Ahmed Valve Implant is safe and effective in lowering IOP for the short term in
      pediatric and adult East African patients with refractory glaucoma. Further
      studies with more patients and longer term follow-up are needed in this
      population.

PMID- 20142984
TI  - Grand challenges for cheminformatics.

PMID- 20142985
TI  - Chemistry publication - making the revolution.
AB  - The advent of the Internet has been the impetus for the Open Access movement, a
      movement focused on expanding access to information principally by reducing the
      costs of journals. I argue here that the Open Access movement has had little
      impact on the chemistry community and has taken our attention away from the real
      opportunity to revolutionize scientific communication. I propose a plan that both
      reduces the total cost of publishing chemistry and enriches the literature
      through incorporation of Open Data. By publishing lots of data, available for
      ready re-use by all scientists, we can radically change the way science is
      communicated and ultimately performed.

PMID- 20142986
TI  - Computer-assisted methods for molecular structure elucidation: realizing a
      spectroscopist's dream.
AB  - BACKGROUND: This article coincides with the 40 year anniversary of the first
      published works devoted to the creation of algorithms for computer-aided
      structure elucidation (CASE). The general principles on which CASE methods are
      based will be reviewed and the present state of the art in this field will be
      described using, as an example, the expert system Structure Elucidator. RESULTS:
      The developers of CASE systems have been forced to overcome many obstacles
      hindering the development of a software application capable of drastically
      reducing the time and effort required to determine the structures of newly
      isolated organic compounds. Large complex molecules of up to 100 or more skeletal
      atoms with topological peculiarity can be quickly identified using the expert
      system Structure Elucidator based on spectral data. Logical analysis of 2D NMR
      data frequently allows for the detection of the presence of COSY and HMBC
      correlations of "nonstandard" length. Fuzzy structure generation provides a
      possibility to obtain the correct solution even in those cases when an unknown
      number of nonstandard correlations of unknown length are present in the spectra.
      The relative stereochemistry of big rigid molecules containing many stereocenters
      can be determined using the StrucEluc system and NOESY/ROESY 2D NMR data for this
      purpose. CONCLUSION: The StrucEluc system continues to be developed in order to
      expand the general applicability, provide improved workflows, usability of the
      system and increased reliability of the results. It is expected that expert
      systems similar to that described in this paper will receive increasing
      acceptance in the next decade and will ultimately be integrated directly to
      analytical instruments for the purpose of organic analysis. Work in this
      direction is in progress. In spite of the fact that many difficulties have
      already been overcome to deliver on the spectroscopist's dream of "fully
      automated structure elucidation" there is still work to do. Nevertheless, as the
      efficiency of expert systems is enhanced the solution of increasingly complex
      structural problems will be achievable.

PMID- 20142987
TI  - A constructive approach for discovering new drug leads: Using a kernel
      methodology for the inverse-QSAR problem.
AB  - BACKGROUND: The inverse-QSAR problem seeks to find a new molecular descriptor
      from which one can recover the structure of a molecule that possess a desired
      activity or property. Surprisingly, there are very few papers providing solutions
      to this problem. It is a difficult problem because the molecular descriptors
      involved with the inverse-QSAR algorithm must adequately address the forward QSAR
      problem for a given biological activity if the subsequent recovery phase is to be
      meaningful. In addition, one should be able to construct a feasible molecule from
      such a descriptor. The difficulty of recovering the molecule from its descriptor
      is the major limitation of most inverse-QSAR methods. RESULTS: In this paper, we
      describe the reversibility of our previously reported descriptor, the vector
      space model molecular descriptor (VSMMD) based on a vector space model that is
      suitable for kernel studies in QSAR modeling. Our inverse-QSAR approach can be
      described using five steps: (1) generate the VSMMD for the compounds in the
      training set; (2) map the VSMMD in the input space to the kernel feature space
      using an appropriate kernel function; (3) design or generate a new point in the
      kernel feature space using a kernel feature space algorithm; (4) map the feature
      space point back to the input space of descriptors using a pre-image
      approximation algorithm; (5) build the molecular structure template using our
      VSMMD molecule recovery algorithm. CONCLUSION: The empirical results reported in
      this paper show that our strategy of using kernel methodology for an inverse
      Quantitative Structure-Activity Relationship is sufficiently powerful to find a
      meaningful solution for practical problems.

PMID- 20142988
TI  - Time to overcome the translational roadblock: Introducing a new open access
      stroke journal.

PMID- 20142989
TI  - Granulocyte-colony stimulating factor for stroke treatment: mechanisms of action
      and efficacy in preclinical studies.
AB  - G-CSF is widely employed for the treatment of chemotherapy-induced neutropenia.
      Recently, neuroprotective effects of G-CSF in animal stroke models were
      discovered including infarct size reduction and enhancement of functional
      recovery. The underlying mechanisms of action of G-CSF in ischemia appear to be a
      direct anti-apoptotic activity in neurons and a neurogenesis inducing capacity.
      Additional effects may be based on the stimulation of new blood-vessel formation,
      the stimulation of immunocompetence and -modulation as well as on bone marrow
      mobilization. In addition to a discussion of these mechanisms, we will review the
      available preclinical studies and analyze their impact on the overall efficacy of
      G-CSF in experimental stroke.

PMID- 20142990
TI  - Long term immunologic consequences of experimental stroke and mucosal tolerance.
AB  - BACKGROUND: An inflammatory insult following middle cerebral artery occlusion
      (MCAO) is associated with a predisposition to develop a deleterious autoimmune
      response to the brain antigen myelin basic protein (MBP). Induction of
      immunologic tolerance to brain antigens prior to MCAO prevents this deleterious
      autoimmune response and is associated with better functional outcome early after
      stroke. In this study, we sought to determine the long term immunologic
      consequences of experimental stroke and induction of mucosal tolerance. METHODS:
      Male Lewis rats were tolerized to MBP or ovalbumin (OVA) by intranasal
      administration prior to MCAO and administration of lipopolysaccharide (LPS).
      Neurological outcome was assessed at set points after MCAO and animals sacrificed
      at 3 months; the immune response to MBP in brain and spleen was determined using
      ELISPOT assay and degree of cellular inflammatory brain infiltrate assessed by
      immunocytochemistry. RESULTS: Animals that developed a pro-inflammatory (TH1)
      response to MBP experienced worse outcome, while those that developed a
      regulatory response (TREG) experienced better outcome. A TREG response in spleen
      was also associated with decreased inflammation and an increase in the number of
      FoxP3 positive cells in brain. In this study, tolerization to MBP prior to MCAO
      was associated with a tendency to develop a TH1 response to MBP by 3 months after
      MCAO. CONCLUSION: These data show that induction of immunological tolerance to
      MBP is associated with improved outcome after stroke. This study, however, raises
      concern about the potential for inadvertent induction of detrimental autoimmunity
      through mucosal administration of antigen.

PMID- 20142991
TI  - Erythropoietin: a multimodal neuroprotective agent.
AB  - The tissue protective functions of the hematopoietic growth factor erythropoietin
      (EPO) are independent of its action on erythropoiesis. EPO and its receptors
      (EPOR) are expressed in multiple brain cells during brain development and
      upregulated in the adult brain after injury. Peripherally administered EPO
      crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti
      oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular
      endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms
      underlie its potent tissue protective effects in experimental models of stroke,
      cerebral hemorrhage, traumatic brain injury, neuroinflammatory and
      neurodegenerative disease. The preclinical data in support of the use of EPO in
      brain disease have already been translated to first clinical pilot studies with
      encouraging results with the use of EPO as a neuroprotective agent.

PMID- 20142993
TI  - Changes in the proteomes of the hemocytes and fat bodies of the flesh fly
      Sarcophaga bullata larvae after infection by Escherichia coli.
AB  - BACKGROUND: Insects have an efficient self-defense system that is based on innate
      immunity. Recent findings have disclosed many parallels between human and insect
      innate immunity, and simultaneously fine differences in the processes between
      various species have been revealed. Studies on the immune systems of various
      insect species may uncover the differences in their host defense strategies.
      RESULTS: We analyzed the proteomes of the hemocytes and fat bodies of Sarcophaga
      bullata larvae after infection by Escherichia coli. The 2-DE gels of the
      hemocytes and fat bodies of infected larvae were compared with those of
      aseptically injured larvae. Our analysis included the construction of protein
      maps of the hemocyte cells and cells from fat bodies, the identification of the
      changed proteins, in response to infection, using LC-MS/MS, and the estimation of
      the trends in expression of these proteins at three time points (30 min, 6 hours
      and 22 hours) after infection. In total, seven changed spots were found in the
      hemocytes, and four changed spots were found in the fat bodies. Three types of
      trends in protein expression were observed. Cofilin and transgelin were
      undetectable at 30 min after infection but were continuously up-regulated in the
      induced larvae after 22 hours. A prophenoloxidase isoform and lectin subunit
      alpha were slightly up-regulated at 30 min after infection, and their protein
      levels reached the highest points after 6 hours but decreased after 22 hours. T
      Complex subunit alpha, GST, ferritin-like protein and an anterior fat body
      protein (regucalcin homologue) were down-regulated at 22 hours after infection.
      CONCLUSIONS: Many proteins identified in our study corresponded to the proteins
      identified in other insects. Compared to the former studies performed in insects,
      we presented 2-D protein maps of the hemocytes and fat bodies and showed the
      trends in expression of the immune-elicited proteins.

PMID- 20142994
TI  - Anesthesia for intra-articular corticosteroid injections in juvenile idiopathic
      arthritis: A survey of pediatric rheumatologists.
AB  - OBJECTIVE: To determine the methods of anesthesia currently being used by
      pediatric rheumatologists when performing intra-articular corticosteroid
      injections (IACI). STUDY DESIGN: A questionnaire was emailed to all members of
      the Childhood Arthritis & Rheumatology Research Alliance, a pediatric
      rheumatology research network in North America. The questionnaire consisted of 11
      questions ranging from procedure technique, treatments prescribed for topical
      anesthesia and oral analgesia, and factors that might affect procedural pain.
      RESULTS: Seventy-four of 161 physicians (46%) responded to the questionnaire. On
      average, each physician injected 33 children (median 25, range 1-160) and 43
      joints (median 30, range 1-150) yearly. Local anesthesia was used in children on
      average >/= 8 years (range 2-16 years), with general anesthesia being more
      frequently used for younger children. All respondents used local anesthesia. The
      most commonly used methods of local anesthesia were EMLA((R) )cream plus
      subcutaneous lidocaine (58.8%), ethyl chloride spray only (39.7%), EMLA((R)
      )cream only (33.8%), subcutaneous lidocaine only (25%), and lidocaine
      iontophoresis only (11.8%). Buffering of the lidocaine was routinely done only
      7.4% of the time. CONCLUSION: Although pediatric rheumatologists in North America
      perform IACI on a large number of patients each year, a wide variety of methods
      are used to deliver local anesthesia with no accepted standard of care. More
      studies are needed to determine the optimal method of local anesthesia delivery
      to minimize pain associated with IACI.

PMID- 20142992
TI  - Models of autoimmune demyelination in the central nervous system: on the way to
      translational medicine.
AB  - Multiple sclerosis (MS) is the most common neurologic disease of young adults. In
      the recent years, our understanding on disease pathomechanisms has considerably
      improved and new therapies have emerged. Yet a cure for this devastating disorder
      is still a far cry away and human resources on ex vivo specimens are limited.
      More than 70 years after its first description, experimental autoimmune
      encephalomyelitis (EAE) remains an important tool to understand concepts of T
      cell mediated autoimmunity as well as the roles of the innate and the humoral
      immune systems. Some EAE models also well reflect mechanisms of tissue damage
      including demyelination, axonal injury and also cortical changes. A limitation of
      the classical EAE model is a neglect of CD8 T cell mediated immune mechanisms.
      Moreover, well characterized models for primary progressive MS or demyelination
      patterns involving primary oligodendrocyte dystrophy are still not available. Yet
      many current therapeutic concepts including glatiramer acetate or natalizumab
      stem from their successful first application in EAE models. New strategies
      include the widespread use of conditional knockout mice to understand the cell
      type specific function of single genes, innovative approaches to establish models
      on the roles of B cells and CD8 T cells as well as on the relation of
      inflammation to primary degeneration. In summary, EAE models continue to play an
      important role in neuroimmunology thereby also stimulating research in other
      fields of the neurosciences and immunobiology.

PMID- 20142995
TI  - Making the 2007-2010 Action Plan work for women in family medicine in the Asia
      Pacific.
AB  - The Wonca Working Party for Women and Family Medicine (WWPWFM) was organized in
      2001 with the following objectives: to identify the key issues for women doctors;
      to review Wonca policies and procedures for equity and transparency; to provide
      opportunities to network at meetings and through the group's listserve and
      website; and to promote women doctors' participation in Wonca initiatives.In
      October 2008, at the Asia Pacific Regional conference, the Wonca Working Party on
      Women in Family Medicine (WWPWFM) held a preconference day and conference
      workshops, building on the success and commitment to initiatives which enhance
      women's participation in Wonca developed in Ontario, Canada (2006) and at the
      Singapore World Congress (2007). At this meeting fifty women workshopped issues
      for women in Family Medicine in the Asia Pacific. Using the Action Plan
      formulated in Singapore (2007) the participants identified key regional issues
      and worked towards a solution.Key issues identified were professional issues,
      training in family medicine and women's health. Solutions were to extend the
      understanding of women's contributions to family medicine, improved career
      pathways for women in family medicine and improving women's participation in
      practices, family medicine organizations and academic meetings.

PMID- 20142996
TI  - ASPM-associated stem cell proliferation is involved in malignant progression of
      gliomas and constitutes an attractive therapeutic target.
AB  - BACKGROUND: ASPM (Abnormal Spindle-like Microcephaly associated) over-expression
      was recently implicated in the development of malignant gliomas. RESULTS: To
      better characterize the involvement of ASPM in gliomas, we investigated the mRNA
      expression in 175 samples, including 8 WHO Grade II, 75 WHO Grade III and 92 WHO
      Grade IV tumors. Aspm expression was strongly correlated with tumor grade and
      increased at recurrence when compared to the initial lesion, whatever the initial
      grade of the primary tumor. ASPM expression also increased over serial passages
      in gliomaspheres in vitro and in mouse xenografts in vivo. Lentivirus-mediated
      shRNA silencing of ASPM resulted in dramatic proliferation arrest and cell death
      in two different gliomasphere models. CONCLUSION: These data suggest that ASPM is
      involved in the malignant progression of gliomas, possibly through expansion of a
      cancer stem cell compartment, and is an attractive therapeutic target in
      glioblastoma multiforme.

PMID- 20142997
TI  - Comparison of lung cancer cell lines representing four histopathological subtypes
      with gene expression profiling using quantitative real-time PCR.
AB  - BACKGROUND: Lung cancers are the most common type of human malignancy and are
      intractable. Lung cancers are generally classified into four histopathological
      subtypes: adenocarcinoma (AD), squamous cell carcinoma (SQ), large cell carcinoma
      (LC), and small cell carcinoma (SC). Molecular biological characterization of
      these subtypes has been performed mainly using DNA microarrays. In this study, we
      compared the gene expression profiles of these four subtypes using twelve human
      lung cancer cell lines and the more reliable quantitative real-time PCR (qPCR).
      RESULTS: We selected 100 genes from public DNA microarray data and examined them
      by DNA microarray analysis in eight test cell lines (A549, ABC-1, EBC-1, LK-2,
      LU65, LU99, STC 1, RERF-LC-MA) and a normal control lung cell line (MRC-9). From
      this, we extracted 19 candidate genes. We quantified the expression of the 19
      genes and a housekeeping gene, GAPDH, with qPCR, using the same eight cell lines
      plus four additional validation lung cancer cell lines (RERF-LC-MS, LC-1/sq, 86
      2, and MS-1-L). Finally, we characterized the four subtypes of lung cancer cell
      lines using principal component analysis (PCA) of gene expression profiling for
      12 of the 19 genes (AMY2A, CDH1, FOXG1, IGSF3, ISL1, MALL, PLAU, RAB25, S100P,
      SLCO4A1, STMN1, and TGM2). The combined PCA and gene pathway analyses suggested
      that these genes were related to cell adhesion, growth, and invasion. S100P in AD
      cells and CDH1 in AD and SQ cells were identified as candidate markers of these
      lung cancer subtypes based on their upregulation and the results of PCA analysis.
      Immunohistochemistry for S100P and RAB25 was closely correlated to gene
      expression. CONCLUSIONS: These results show that the four subtypes, represented
      by 12 lung cancer cell lines, were well characterized using qPCR and PCA for the
      12 genes examined. Certain genes, in particular S100P and CDH1, may be especially
      important for distinguishing the different subtypes. Our results confirm that
      qPCR and PCA analysis provide a useful tool for characterizing cancer cell
      subtypes, and we discuss the possible clinical applications of this approach.

PMID- 20142998
TI  - Metathesis in the generation of low-temperature gas in marine shales.
AB  - The recent report of low-temperature catalytic gas from marine shales took on
      additional significance with the subsequent disclosure of natural gas and low
      temperature gas at or near thermodynamic equilibrium in methane, ethane, and
      propane. It is important because thermal cracking, the presumed source of natural
      gas, cannot generate these hydrocarbons at equilibrium nor can it bring them to
      equilibrium over geologic time. The source of equilibrium and the source of
      natural gas are either the same (generation under equilibrium control) or closely
      associated. Here we report the catalytic interconversion of hydrocarbons
      (metathesis) as the source of equilibrium in experiments with Cretaceous Mowry
      shale at 100 degrees C. Focus was on two metathetic equilibria: methane, ethane,
      and propane, reported earlier, Q (K = [(C(1))*(C(3))]/[(C(2))(2)]), and between
      these hydrocarbons and n-butane, Q* (K = [(C(1))*(n-C(4))]/[(C(2))*(C(3))]),
      reported here for the first time. Two observations stand out. Initial hydrocarbon
      products are near equilibrium and have maximum average molecular weights (AMW).
      Over time, products fall from equilibrium and AMW in concert. It is consistent
      with metathesis splitting olefin intermediates [C(n)] to smaller intermediates
      (fission) as gas generation creates open catalytic sites ([ ]): [C(n)] + [ ] -->
      [C(n-m)] + [C(m)]. Fission rates increasing exponentially with olefin molecular
      weight could contribute to these effects. AMW would fall over time, and selective
      fission of [C(3)] and [n-C(4)] would draw Q and Q* from equilibrium. The results
      support metathesis as the source of thermodynamic equilibrium in natural gas.

PMID- 20143000
TI  - From rehabilitation to remission in ankylosing spondylitis.

PMID- 20143001
TI  - [Cardiac involvement in rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized
      by a chronic inflammatory process mainly leading to destruction of synovial
      membrane of small and major diarthrodial joints. The prevalence of RA within the
      general adult population is about 1% and female subjects in fertile age result
      mostly involved. It's an invalidating disease, associated with changes in life
      quality and a reduced life expectancy. Moreover, we can observe an increased
      mortality rate in this population early after the onset of the disease. The
      mortality excess can be partially due to infective, gastrointestinal, renal or
      pulmonary complications and malignancy (mainly lung cancer and non-Hodgkin
      lymphoma). Among extra-articular complications, cardiovascular (CV) involvement
      represents one of the leading causes of morbidity and mortality. Every cardiac
      structure can be affected by different pathogenic pathways: heart valves,
      conduction system, myocardium, endocardium, pericardium and coronary arteries.
      Consequently, different clinical manifestations can be detected, including:
      pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of
      conduction system, coronaropathies and ischemic cardiopathy, valvular disease,
      pulmonary hypertension and heart failure. Considering that early cardiac
      involvement negatively affects the prognosis, it is mandatory to identify high CV
      risk RA patients to better define long-term management of this population.

PMID- 20143002
TI  - [TNF-alpha and insulin-resistance: metabolic effects of in vivo therapeutic
      blockade].
AB  - Insulin resistance is a key pathophysiologic feature of obesity, type 2 diabetes
      mellitus and prediabetic states (impaired fasting glucose, impaired glucose
      tolerance). TNF-alpha, a proinflammatory cytokine, plays an important role in the
      pathogenesis of insulin resistance associated with inflammation during the course
      of rheumatic diseases. Therapies aimed at neutralizing TNF-alpha, such as the
      monoclonal antibody infliximab, represent a relatively new approach in the
      treatment of rheumatic diseases and allow to obtain significant results in terms
      of control of the inflammatory process. In this article we reviewed the
      scientific evidence published in the literature about a potential role of TNF
      alpha blockade in improving insulin resistance in rheumatic patients without
      diabetes.

PMID- 20143003
TI  - [Guidelines for the diagnosis, prevention and treatment of osteoporosis].
AB  - The guidelines for the osteoporosis management were first drafted by a working
      group and then critically evaluated by the board of SIOMMMS. The most relevant
      points are: DEFINITION: Osteoporosis is defined as a quantitative and qualitative
      deterioration of bone tissue leading to increased risk of fracture.
      Postmenopausal and senile osteoporosis are defined as primitive. DIAGNOSIS: The
      cornerstone for the diagnosis of osteoporosis is the measurement of bone mineral
      density (BMD) by DXA (dual-energy X-ray absortiometry) at the femoral neck with T
      score values <-2.5, following the WHO definition. Other DXA sites or technologies
      for measuring bone mass are also acceptable when the former is not accessible. A
      BMD evaluation is recommended to all women above 65 years of age. At younger age
      or in man the bone assessment is recommended only in subjects with specific risk
      factors. A control of bone mass measurement is seldom required before 2 years.
      DIFFERENTIAL DIAGNOSIS: A few biochemical tests such as serum and urinary
      calcium, protein electrophoresis, serum creatinine and ESR are usually sufficient
      to exclude most secondary types of osteoporosis. The value of the so called bone
      turnover markers for the diagnosis and follow-up of osteoporosis remains
      uncertain. Several secondary forms of osteoporosis require a specific diagnostic
      and therapeutic management. PREVENTION: The osteoporosis prevention should be
      based on the elimination of specific risk factors such as inadequate calcium and
      vitamin D intake, smoking and sedentary life. The use of pharmacological agents
      in subjects with BMD values >-2.5 is usually not justified. Pharmacological
      intervention: The use of drugs registered for the treatment of osteoporosis are
      recommended when the benefits overcome the risk. This is the case only when the
      risk of fracture is rather high. FRAX is recognized as a useful tool for easily
      estimate the long-term fracture risk. SIOMMMS with these guidelines is committed
      to validate and further develop this diagnostic tool.

PMID- 20143004
TI  - Demographic and clinical aspects of an Italian patient population with chronic
      fatigue syndrome.
AB  - OBJECTIVE: The purpose of this study was to investigate demographic and clinical
      aspects of a group of Italian patients with Chronic Fatigue Syndrome (CFS) which
      have not yet been described, in order to compare them with International
      literature, and to better define certain clinical aspects of the syndrome with
      respect to the Fukuda et al. case definition. METHODS: A detailed questionnaire
      was sent to patients with certified CFS diagnosed in a referral center and the
      data were collected two weeks later. RESULTS AND CONCLUSIONS: Besides persistent
      fatigue, a clinical syndrome with infectious, neurological and rheumatological
      characteristics is outlined from the data. Demographic characteristics of Italian
      patients are very similar to those described in international literature. Therapy
      has yet to be validated with evidence-based studies in Italy. Studies on the
      prevalence of CFS in Italy are lacking and would be useful to better define the
      syndrome in this Mediterranean population.

PMID- 20143005
TI  - [The support of the ultrasonography of the shoulder in the diagnosis of
      polymyalgia rheumatica with normal erythrocyte sedimentation rate].
AB  - Polymyalgia rheumatica (PMR) is a chronic inflammatory syndrome that affects the
      elderly population and whose diagnosis is mainly based on clinical criteria
      taking little advantage of the latest innovatory methods of diagnostic imaging,
      for instance ultrasonography. Although it is generally characterised by
      increasing of inflammation values as well as pain and stiffness on the shoulder
      and pelvic girdles, there is a significant percentage of patients with PMR whose
      erythrocyte sedimentation rate (ESR) is normal; in this case to make a diagnosis
      is difficult. The purpose of our study is to demonstrate how useful ultrasound
      investigations on the shoulders joints could be in order to make a diagnosis of
      PMR, especially for those patients with atypical normal ESR. Our case control
      study included 23 patients with atypical PMR and 88 patients with standard
      symptomatic PMR; both groups underwent shoulder ultrasound scans before receiving
      steroid therapy. As it has been previously shown, the ultrasound method is able
      to detect distinctive aspects in the joints and tissues of the patients with PMR;
      so that we could find that 90% of the patients with PMR of both groups suffered
      from bilateral subdeltoid bursitis. This disorder is seldom found in healthy
      people and consequently its presence could be considered a useful diagnostic
      test/check for/of PMR independently from ESR values.

PMID- 20143006
TI  - [Subclinical atherosclerosis in patients with psoriatic arthritis: a case-control
      study. Preliminary data].
AB  - OBJECTIVE: The aim of this study was to evaluate the prevalence of subclinical
      atherosclerosis in patients with psoriatic arthritis (PsA), correlated with some
      traditional risk factors of atherosclerosis and with PsA-related disease factors.
      METHODS: Forty-one patients and 41 healthy subjects were evaluated for intima
      media thickness (IMT) and flow-mediated dilation (FMD), using carotid duplex
      scanning. IMT values were expressed like IMT mean (cumulative mean of all the IMT
      mean) and M-MAX (cumulative mean of all the higher IMT). Subclinical
      atherosclerosis markers were correlated with age, body mass index (BMI) and blood
      pressure in both groups, with duration of arthritis, duration of psoriasis,
      tender and swollen joints, BASDAI (Bath Ankylosing Spondylitis Disease Activity
      Index), BASFI (Bath Ankylosing Spondylitis Functional Index), erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP) in patients. RESULTS: IMT
      mean and M-MAX were both higher in PsA patients compared with controls (0.7+/
      0.15 vs 0.62+/-0.09 mm; p<0.01 and 0.86+/-0.21 vs. 0.74+/-0.13 mm; p<0.01
      respectively). FMD was smaller in patients than in controls (5.9+/-2 vs 7.5+/
      2.8%; p<0.01). Univariate analysis showed a correlation between IMT mean and SBP
      (r=0.217; p=0.05) and a correlation between M-MAX and age (r=0.392; p<0.001), BMI
      (r=0.252; p<0.05), SBP (r=0.446; p<0.001) in both groups. In PsA patients M-MAX
      resulted correlated with ESR (r=0.338; p<0.05) and BASDAI (r=0.322; p<0.05).
      CONCLUSIONS: PsA patients exhibited endothelial dysfunctions which is an early
      marker of subclinical atherosclerosis, as well as an higher IMT. An interesting
      correlation between M-MAX and PsA activity index (ESR and BASDAI) was found.

PMID- 20143007
TI  - Unexpected and persistent depletion of B lymphocytes CD20 following a minimum
      dose of anti-CD20 antibody (Rituximab).
AB  - This study describes a woman patient suffering from rheumatoid arthritis which
      was resistant to treatment with the most commonly used DMARDs and anti-TNF alfa
      drugs, however following the administration of a minimum dose of Rituximab the
      patient showed a persistent and complete depletion of CD 20 lymphocytes. The dose
      of Rituximab administered to the patient was halted at 50 mg due to the onset of
      an allergic reaction. Based on these observations, a number of important
      speculations are possible, which however would require a larger number of case
      histories for their confirmation.

PMID- 20143008
TI  - [The ultrasound assessment of the psoriatic arthritis: from joint to skin].
AB  - There is a growing number of papers investigating the diagnostic potential of
      ultrasonography in the assessment of patients with psoriatic arthritis and
      supporting its higher sensitivity over clinical examination in the diagnosis of
      synovitis, enthesitis and tenosynovitis. Less attention has been paid on both
      skin and nail, frequently involved in this condition. The aim of this paper is to
      show the potential of ultrasound in a multi-target assessment (joints, tendons,
      entesis, skin and nails) in patients with psoriatic arthritis, using the last
      generation ultrasound equipment.

PMID- 20143009
TI  - Clinical profile of patients with lupus nephritis.

PMID- 20143010
TI  - Thrombin receptors in vascular smooth muscle cells - function and regulation by
      vasodilatory prostaglandins.
AB  - The vast majority of thrombin (>95%) is generated after clotting is completed,
      suggesting that thrombin formation serves purposes beyond coagulation, such as
      tissue repair after vessel injury. Two types of vascular thrombin binding sites
      exist: protease-activated receptors (PARs) and thrombomodulin (TM). Their
      expression is low in contractile vascular smooth muscle cells (SMC), the
      dominating subendothelial cell population, but becomes markedly up-regulated upon
      injury. In human SMC, PAR-1, PAR-3, and PAR-4 mediate thrombin-induced
      proliferation, migration and matrix biosynthesis as well as generation of
      inflammatory and growth-promoting mediators. Thrombin-responsive PARs are
      transcriptionally down-regulated in human vascular SMC by vasodilatory
      prostaglandins (PGI2/PGE2). For PAR-1 and PAR-3 this mechanism involves cAMP
      dependent inactivation of the transcription factor NFAT. The human PAR-4 promoter
      does not possess NFAT recognition motifs suggesting involvement of other cAMP
      regulated effectors. Unlike PARs, TM is induced in SMC exposed to vasodilatory
      prostaglandins. Enhanced thrombin binding to TM might ameliorate PAR-mediated SMC
      stimulation. Also expressed in human SMC is the endothelial protein C receptor
      (EPCR), which serves as an anchor to facilitate generation of activated protein C
      (aPC) by TM-bound thrombin. Whether prostaglandins affect aPC-generation is not
      known. In SMC, thrombin and aPC act synergistically via PAR-1 to modify tissue
      remodelling, in contrast to their antagonistic interaction in the coagulation
      pathways. Overall, this will contribute to plaque stability and wound healing.
      The processes outlined here are likely to become clinically relevant after up
      regulation of vascular cyclooxygenase2, the rate limiting step in vascular
      PGE2/PGI2 biosynthesis, such as in advanced atherosclerosis and acute coronary
      syndromes.

PMID- 20143011
TI  - Comparison between the growth of Brazilian children and adolescents and the
      reference growth charts: data from a Brazilian project.
AB  - OBJECTIVE: To compare the growth of Brazilian children and adolescents with
      reference growth charts. METHODS: School-based cross-sectional study involving
      41,654 students (23,328 boys and 18,326 girls) aged 7 to 17 years. Physical
      growth variables (body weight, height) and body mass index (BMI) were measured.
      Height, 50th percentile, and BMI, 85th percentile, were compared with the World
      Health Organization (WHO) reference values, and weight, 50th percentile, was
      compared with the Centers for Disease Control and Prevention (CDC) growth charts.
      RESULTS: Mean height and body weight of Brazilian schoolchildren were generally
      higher than the WHO and CDC reference values for both genders at most ages. BMI
      values of Brazilian schoolchildren were significantly lower than the WHO obesity
      values at all ages. CONCLUSION: The growth in body weight, height, and BMI of
      children and adolescents in the urban area of Brazil is increasingly similar to
      those reported in developed countries. Further prospective studies should be
      conducted in Brazil comparing their results with the international growth charts
      to enable more accurate inferences.

PMID- 20143012
TI  - [The sampling survey of teeth defect and denture restoration among 1579 middle
      aged and elder people in Shanghai].
AB  - PURPOSE: To investigate the condition of teeth defect and denture restoration
      among the middle aged and elder people in Shanghai and to analyse the variation
      tendency so as to provide relevant policy basis for the government. METHODS:
      Multistage stratification isasteric random sample was used to acquire the teeth
      defect and denture restoration information among 791 people from 35 to 44 and 788
      people from 65 to 74 years old, respectively. SPSS13.0 software package was used
      for data analysis. RESULTS: The teeth defect rate of the middle aged and elder
      people in Shanghai was 21.0% and 81.0%, respectively. The mean permanent teeth
      number was 28.9 and 19.5. The edentulous rate of the elder people was 10.8%. The
      defect rate was highest in the molar area, and lowest in the canine agra. The
      denture restoration rate of the middle aged and elder people was 59.6% and 61.7%,
      respectively. The rate of the removable denture restoration was higher than that
      of the fixed denture. The rate of full denture, fixed denture and informal fixed
      bridge restoration in the suburb area was higher than that in the urban
      area(P<0.01). CONCLUSIONS: The condition of teeth defect and denture restoration
      among middle aged and elder people in Shanghai is still unsatisfactory even
      though it has been getting better in the last decade. It is suggested that the
      government take efforts to lessen the teeth defect by control of caries and
      periodontal disease, and to improve the restoration level of the middle aged and
      elder people.

PMID- 20143013
TI  - [Stress distribution of two kinds of fixed prosthese supported by four or six
      dental implants in edentulous mandible].
AB  - PURPOSE: To investigate the stress distribution of 2 kinds of distal cantilevered
      fixed prostheses supported by 4 or 6 dental implants in edentulous mandible with
      three-dimensional finite element method. METHODS: The first design was 4 implants
      supported fixed prostheses with 6mm distal cantilever; the second design was 6
      implants supported fixed prostheses with 6mm distal cantilever. Vertical force of
      100 N was applied to the distal cantilever of fixed prostheses. RESULTS: The bone
      stress was concentrated at the cortex of mandible. The maximum bone stress was at
      the cortex near the second implants from the point that the vertical force was
      applied. The maximum implant stress was at the terminal and medium implant
      prostheses interface. CONCLUSIONS: The bone around the terminal implant is easily
      to absorb and the terminal and medium implants are easily to fracture. The
      maximum stress of the implants and prostheses of two kinds of design are almost
      same(239Mpa). Two kinds of design can be applied in the clinic. 6 mm distal
      cantilevered fixed prostheses supported by 6 implants have the less bone stress
      than 4 mm distal cantilevered fixed prostheses in edentulous mandible.

PMID- 20143014
TI  - [The restoration of large mandibular defect with telescopic crown- retained
      prostheses: report of one case].
AB  - PURPOSE: To investigate the feasibility and clinical result of restoration of
      large mandibular defect with telescopic crown- retained prostheses. METHODS: One
      patient who suffered from large mandibular defect was restored with fixed
      removable prostheses, with the telescope crowns as the retainer on the lower
      right second molar and left first, second molar. RESULTS: The prostheses with
      telescope crown could be seated freely in the patient's mouth. The function of
      mastication and phonetics were restored. The appearance of the patient was also
      improved. CONCLUSION: The restoration of large mandibular defect with telescopic
      crown- retained prostheses is feasible, with satisfactory clinical result.

PMID- 20143015
TI  - [Noise level in dental laboratory practice].
AB  - PURPOSE: Dental technicians are exposed to different noises. The aim of this
      study was to determine the noise level produced by different dental laboratory
      handpieces and special equipments in one dental lab. METHODS: The noise level
      produced by two dental laboratory handpieces(Kavo K9, NSK Vmax) was measured at
      distance of 15cm, 30cm and 45cm in free-running and different working conditions.
      Additionally, the noise level produced by some dental laboratory equipments and
      procedures were also measured both near the technician's ear and 1.5 meters away.
      The noise level was determined using a precious sound level meter. RESULTS: The
      mean value of noise level of the two dental laboratory handpieces measured at all
      distances and in all conditions was between 61 to 83 dB. The noise level produced
      by some dental laboratory equipments were much higher, with high-speed metal
      cutting, steam cleaning and power pillo trimmer exceeding 90dB. Noise level
      inside the denture fabrication room was between 65 to 83 dB. CONCLUSIONS: The
      noise level in the dental laboratory is considered to be a potential risk causing
      hearing loss. Regular audiometry checking up should be carried out among the
      dental technicians and ear protectors must be used during work.

PMID- 20143016
TI  - [Presurgical nasoalveolar molding in the treatment of infants with bilateral
      complete cleft lip and palate].
AB  - PURPOSE: To evaluate the curative effect of presurgical nasoalveolar molding
      (NAM) in the treatment of infants with bilateral complete cleft lip and palate
      (BCLP). METHODS: Nine infants with BCLP were included. Presurgical alveolar
      molding was used to bring the premaxilla back into proper alignment with the
      lateral segments in the maxilla arch. Presurgical nasal molding produced tissue
      expansion of the short columella and corrected the nasal tip cartilages. Up to 5
      months of active treatment was needed before lip repair. Student's t test was
      used for data analysis with SPSS 15.0 software package. RESULTS: After
      presurgical NAM in 9 infants with BCLP, the posterior lateral alveolar segments
      were aligned while retracting the premaxilla, the premaxilla had been returned
      from 37.64mm to 29.94mm within the maxillary arch (P<0.01). The nasal alar base
      width was significantly reduced following NAM(P<0.05). The columella was
      nonsurgically lengthened from 1.13mm to 3.78mm(P<0.05). CONCLUSION: In order to
      obtain satisfactory lip-nose configuration for BCLP, presurgical NAM is useful in
      cleft lip and palate team approach.

PMID- 20143017
TI  - [The effect of first premolar extraction on third molar angulation and eruption
      space].
AB  - PURPOSE: To study the influence of the first premolar extraction on the
      angulation and eruption space of third molar. METHODS: One hundred and twenty
      patients cases of Class I malocclusions were divided into 2 groups by age, who
      were treated with extraction and non-extraction respectively. The following
      values was measured: angle of cusp line between the second and third molar(alpha
      angle),impact state and depth, distance from Rickett's Xi to distal cusp of third
      mandibular molar along the occlusal plane(Xi-LTM), anterior border of ramus to
      the third mandibular molar(R-LTM), distance from projection of distal contact
      point of maxillary third molar to intersection of pterygoid vertical on occlusal
      plane (PTV-UTM). The change between pre- and post-treatment was calculated and
      analyzed with SPSS10.0 software package. alpha angle, Xi-LTM, R-LTM, R-LTM were
      tested with independent-sample t test, impact state and depth was tested with Chi
      square test. Influence of age on the values was also evaluated. RESULTS: In
      younger group, changes of mandibular alpha angle and Xi-LTM in extraction group
      was 7.16 degrees and 3.22mm, but in elder group, these changes was 2.42 degrees
      and 2.10mm, all values were significantly larger than non-extraction group
      (P<0.05). Impact state and depth of third mandibular molar improved in extraction
      group, while there was no significant changes in the maxilla. CONCLUSIONS: The
      third mandibular molar becomes upright and distal movement after first premolar
      extraction. The possibility of the third mandibular molar impaction is decreased,
      but the effect on the maxilla is not significant.

PMID- 20143018
TI  - [The relationship between the infant nursing bottle caries and the feeding
      patterns, oral health behavior and parents' oral health information].
AB  - PURPOSE: To investigate the relationship between the infant nursing bottle caries
      in city community and the feeding patterns, oral health behavior, parents' oral
      health information, and to provide scientific basis for future infant nursing
      bottle caries prevention. METHODS: Three hundred infants aged 6, 7, 12, 18 months
      in April 2009 in Bai Guan Street Community Hospital Shangyu City were enrolled in
      this study, nursing bottle caries were examined and recorded. Questionnaires on
      infant basic data, feeding patterns, oral health behavior, parents' oral health
      information were asked and recorded in these 300 parents. The relationship was
      analyzed between the infant nursing bottle caries and the questionnaires by Chi
      square test with the SPSS14.0 software package. RESULTS: The infant nursing
      bottle caries correlated obviously with the habit of sleeping with the nursing
      bottle or mammary papilla in mouth, and did not correlate with the breast or
      artificial feeding patterns. The occurrence rate of infant nursing bottle caries
      was significantly lower in the infants with oral health behavior than those
      without oral health behavior. After feeding food, more parents feed the infants
      with little plain boiled water than clean the infant oral cavity with finger cap
      wet carbasus. 56.7% of parents had no acknowledge of danger of infant nursing
      bottle caries. CONCLUSION: There is some correlation between the infant nursing
      bottle caries and the feeding patterns, oral health behavior, parents' oral
      health information.

PMID- 20143019
TI  - [The effect of first premolar extraction on vertical dimension in skeletal Class
      I patients].
AB  - PURPOSE: To evaluate the vertical changes in Class I patients treated with first
      premolar extraction and to compare these changes with those without extraction.
      METHODS: Each group had 25 cases.One group was treated with first premolar
      extraction and the other without extraction. Lateral cephalograms were taken both
      pretreatment and posttreatment. All the films were traced and measured. To
      determine the vertical dimension changes due to treatment and to compare
      differences between the 2 groups, paired and unpaired t tests were performed with
      SPSS 16.0 software package, respectively. RESULTS: There was no significant
      difference in FH-MP, Yaxis, S-Go, S-Go/N-Me and ANS-Me/N-Me in both group after
      treatment. Both groups had increase in N-Me , but the change was comparatively
      greater in the extraction group. The extraction group showed more vertical
      movement of the mandibular first molars than the non-extraction group.Both groups
      showed mesial movement of the maxillary first molars and central incisors,but no
      significant difference was found. CONCLUSIONS: Both groups have increase in
      linear vertical dimensions. The changes in vertical dimension is greater in the
      extraction group, but there is no further change in the mandibular plane angle.

PMID- 20143020
TI  - [Clinical application of 3DX CT in diagnosis and treatment of unerupted and
      impacted teeth].
AB  - PURPOSE: To evaluate the clinical value of 3DX CT in the diagnosis and treatment
      of unerupted and impacted teeth. METHODS: Eighty-four unerupted and impacted
      teeth from 66 patients were examined with cone beam CT, and 3-dimentional image
      was obtained for analysis. RESULTS: The 3DX CT image could clearly demonstrate
      the location of the unerupted and impacted teeth in the bone,including the labial
      or palatal location ,crown, root and the relationship between the impacted teeth
      and adjacent important structures. CONCLUSION: 3DX CT can be applied before
      surgical and orthodontic treatment.

PMID- 20143021
TI  - [Effect of cyclic strain on cell morphology, viability and proliferation of human
      dental pulp cells in vitro].
AB  - PURPOSE: To investigate the effect of mechanical strain on cell morphology,
      viability and proliferation of human dental pulp cells in vitro. METHODS: Human
      dental pulp cells were cultured and subjected to 2% or 8% strain with Flexcell
      Tension Plus System for 0.5 hour, 12 hours and 24 hours, respectively, and then
      the cell morphology, viability and proliferation were examined by phase contrast
      microscope, trypan-blue staining and MTT method. The results were analyzed by one
      way ANOVA with SPSS16.0 software package. RESULTS: Cells were stretched and
      aligned perpendicular to the direction of the force applied with obvious pole
      formation under the tested condition. The viability and proliferation of the
      cells subjected 2% or 8% strain were significantly higher than that of untreated
      cells, which reached the peak at 12 hours. The proliferation of the cells
      increased after loading strain which was significantly higher than that in the
      control by 2% stain subjected for 24 hours (P<0.01). CONCLUSIONS: Cyclic strain
      could affect morphology, viability and proliferation of in vitro cultured human
      dental pulp cells in a magnitude/time dependent manner.

PMID- 20143022
TI  - [In vitro study on the amelioration of T cell-mediated osteoclastogenesis by anti
      RANKL-polyclonal antibody].
AB  - PURPOSE: To characterize the effect of receptor activator of NF-kB ligand (RANKL)
      polyclonal antibody on T cell-mediated osteoclasogenesis. METHODS: Rabbit anti
      rat RANKL polyclonal IgG antibody was performed, performing recombinated mouse
      RANKL-induced osteoclastogenesis in different antibody doses
      (1microg/mL,5microg/mL and 10microg/mL), the number of TRAP positive multinuclear
      cells (cells/well) was calculated under microscopy. The cervical lymph nodes in
      rats were enriched T-cells for in vitro experiments. The T cell-mediated
      osteoclastogenesis was tested by co-culture assay of RAW 264.7 cells with
      formalin-fixed T cell or T cell supernatant, the number of TRAP positive
      multinuclear cells (cells/well) was calculated under microscopy. In some
      experiments, the concentration of sRANKL (soluble RANKL) was measured in
      supernatant by ELISA (pg/mL). SPSS 11.5 software package was used for statistical
      analysis. RESULTS: Rabbit anti-rat RANKL antibody inhibited osteoclastogenesis by
      recombined mouse RANKL-induced, and dose-dependent; Anti-RANKL antibody inhibited
      T cell and culture supernatant induced osteoclastogensis, significantly different
      from that in the group without antibody(P<0.05), and dose-dependent; Anti-RANKL
      specific antibody also markedly reduced sRANKL concentration in supernatant,
      significantly different from that in the control group without antibody(P<0.05).
      CONCLUSIONS: Anti-RANKL specific antibody blocks direct effect of RANKL and
      interferes with immune T cell-mediated bone resorption by reduction of sRANKL
      level.

PMID- 20143023
TI  - [Stress distribution of surgically assisted tooth-borne rapid maxillary expansion
      via three different types of osteotomies].
AB  - PURPOSE: To investigate the stress distribution of craniofacial bones during
      surgically assisted tooth-borne rapid maxillary expansion (SARME) via three
      different osteotomies. METHODS: Three-dimensional finite element model of
      craniofacial bones with a tooth-borne appliance was generated. According to the
      different osteotomies, the models were categorized as three groups: Type I
      isolated midpalatal osteotomy, Type II-Le Fort I and midpalatal osteotomies, Type
      III-Le Fort I and midpalatal osteotomies and bilateral pterygomaxillary
      disjunction. In all three models, with 4 different displacements, von-Mises
      stress was measured and analysed at 11 anatomical structures of the craniofacial
      bones. RESULTS: An obvious reduction of the stress was observed followed by the
      larger extent of the surgery. The maximum stress of the bones was only noticed in
      Type I model. Stress on lamina of the pterygoid acutely increased in the Type II
      model compared with the Type I model. In Type III model, after separation of the
      pterygomaxillary junctions, stress on lamina of the pterygoid decreased rapidly
      and meanwhile stressed on the majority of the midfacial bones also decreased. In
      Type III osteotomies, anatomical structures of the upper craniofacial bones
      suffered from an increase of the stress. CONCLUSIONS: Surgical procedures would
      be of great help to reduce the stress on the craniofacial region in the rapid
      maxillary expansion postoperatively. Fractures of the cranial base may occur at a
      greater chance because of stress focusing on lamina of the pterygoid. So,
      separation of the pterygomaxillary junctions during the operation is suggested.
      Increasing stress on the upper craniofacial bones can be observed after
      separation of the pterygomaxillary junctions due to changes of stress
      transduction pathways.

PMID- 20143024
TI  - [The effect of dental plaque in cyclosporin A-induced gingival overgrowth].
AB  - PURPOSE: To evaluate the role of dental plaque in cyclosporin A(CsA)-induced
      gingival overgrowth. METHODS: After extraction of half of the maxillary molars,
      twenty male Sprague-Dawley rats were assigned to a CsA-injection group (10mg/k x
      d) or a control group. Ten rats per group were sacrificed at week 4. The gingival
      width was measured under a stereomicroscope. Gingival specimens were taken, and
      the linear measurements were made with the help of software Image Pro-plus 6.0.
      The data was analyzed with SAS 6.12 software package. RESULTS: The gingival width
      of the CsA group was significantly greater than the control group in both
      macroscopic analysis and histomorphometrical analysis (P<0.05). CONCLUSIONS:
      Dental plaque seems not to be a essential but to be a co-factor for the CsA
      induced gingival overgrowth.

PMID- 20143025
TI  - [Microleakage of various cementing agents for casting ceramics].
AB  - PURPOSE: To observe and compare the microleakage of different composite resin
      cement systems for IPS Empress 2 ceramics base. METHODS: Sixteen healthy non
      carious human molars were selected in the study. Class V ceramic inlay was
      prepared by IPS Empress 2 ceramics. The samples were divided into two groups,
      eight in each group. RelyX Unicem and Variolink 2 were used for bonding
      respectively in 2 groups. All specimens were stored in water at 37 degrees
      centigrade for 24 hours, then the specimens were subjected to 500 thermocycles
      ranging from 5 degrees centigrade to 55 degrees centigrade. Eight specimens in
      each group were evaluated by dye penetration. The microleakage was examined with
      light microscope. Statistical analysis was performed with SPSS11.0 software
      package. RESULTS: Enamel margins exhibited lower leakage than dentin margins by
      using two cementing agents for casting ceramics (P<0.05). The depth of dye for
      Variolink 2 and RelyX Unicem at enamel and dentin was not significantly different
      (P>0.05). CONCLUSIONS: The microleakage of Variolink 2 and RelyX Unicem for IPS
      Empress 2 ceramics base has similar sealing abilities.

PMID- 20143026
TI  - [The effect of simvastatin on osteoblastic bionomics of rats].
AB  - PURPOSE: To study the effect of simvastatin on osteoblast proliferation,
      differentiation and mineralization and to explore the mechanism of stimulation of
      bone formation by simvastatin. METHODS: Six 8-hour healthy SD rats were used for
      the experiment. In order to harvest vital osteoblast, this research modified the
      traditional tissue piece method to culture primary osteoblast of rat
      calvarias.The effect of simvastatin in different
      concentration(1.0micromol/L,0.5micromol/L,0.25micromol/L,0.125micromol/L) on
      osteoblast was measured using MTT to assay osteoblasts proliferation, alkaline
      phosphatase activity of osteoblasts was measured, the level of osteocalcin (OC)
      was detected, the capacity of mineralization was investigated by counting the
      mean mineralization area with Image-Pro Plus 6.0.The data was analyzed with SPSS
      13.0 software package for one-way ANOVA. RESULTS: Compared with the control
      group, the osteoblasts proliferation was inhibited in the experimental groups in
      a dose-dependent manner. It showed that the alkaline phosphatase activity of
      osteoblast was increased in all experimental groups. The level of OC of
      osteoblasts showed a significant increase in all treatment groups. With regard to
      osteoblast capability of mineralization, the mineralization area was also
      increased, compared with the control group (P<0.05). CONCLUSION: Simvastatin
      inhabits the proliferation of osteoblasts in vitro, but promotes differentiation
      and mineralization of osteoblast.

PMID- 20143027
TI  - [Effect of hyperglycemia on glucose uptake of rat mandibular osteoblasts].
AB  - PURPOSE: Growing evidence shows an association between diabetes mellitus and
      alveolar bone loss. As abnormal cellular glucose uptake and metabolism are partly
      involved in diabetic complications, this study was undertaken to explore the
      effect of hyperglycemia on glucose uptake, glucose transporter1 (GLUT1)
      expression induced by insulin of rat mandibular osteoblasts. METHODS: Primary
      osteoblasts were isolated and cultured. The cells were incubated for 48h with
      medium containing 5.5mmol/L and 16.5mmol/L glucose respectively,then treated with
      or without insulin for 24h. Glucose uptake was detected by using (18)F-FDG in the
      cells and GLUT1 expression levels were evaluated by Western blotting analysis.
      One-way ANOVA and t test were performed using SPSS13.0 software package. RESULTS:
      The results showed that with 16.5mmol/L glucose, glucose uptake was not changed
      significantly, but GLUT1 expression was increased by 35% (P<0.01), insulin had no
      significant effect on glucose uptake, but it decreased GLUT1 expression by 33%
      (P<0.01). CONCLUSIONS: It is concluded that hyperglycemia can induce insulin
      resistance of osteoblasts, in which alteration in transport activity and function
      of GLUT1 might be involved.

PMID- 20143028
TI  - [The influence of different opaque thickness on the bond strength of porcelain
      fused-to metal restoration].
AB  - PURPOSE: To study the influence of different opaque thickness on the bond
      strength of porcelain-fused-to metal (PFM) restorations. METHODS: The testing
      sheets were made as the samples of ISO9693. With different sintering temperature
      and different opaque thickness on the bond strength of PFM restorations, the
      primary pressure of porcelain crack was measured by using three-points-bending
      test. Statistical analysis was carried out using a SPSS 10.0 software package. A
      post hoc multiple comparison test (Student-Newman-Keuls) was performed to
      evaluate the differences between the individual groups. RESULTS: In low sintering
      temperature group, the thin layer of opaque significantly improved the bond
      strength compared with thick layer of opaque (P<0.05). In high sintering
      temperature group, the thickness of opaque has no significant influence on the
      PFM bonding strength. Using the opaque, the bonding strength was better than
      those without opaque. CONCLUSION: The thickness of opaque has a little influence
      on the PFM bonding strength.

PMID- 20143029
TI  - [Effect of post space preparation on the sealability of root canal filled with 3
      filling methods].
AB  - PURPOSE: To evaluate the effect of post space preparation on the sealability of
      canals filled with 3 filling methods. METHODS: The crowns of 24 human anterior
      teeth extracted for periodontal disease were removed and the working length of
      canal was unified to be 16 mm. The teeth were divided into 3 groups at random:
      group A (normal temperature flow gutta-percha single-corn technique with
      GuttaFlow), group B (lateral compaction technique with AH Plus) and group C (warm
      vertical condensation technique with AH Plus+ BeeFill thermoplastics system). The
      root canals were prepared and filled according to different system. Microleakage
      of root canals of pre-post space preparation was measured with a fluid transport
      study one week after filling. Then the post space was prepared using 1#- 6# G
      drill step by step, by leaving 4 mm of root canal filling material apically.
      Microleakage of root canals of post-dowel space preparation was measured again.
      SPSS13.0 software package was used for statistical analysis. RESULTS: No
      difference was found between pre-post space preparation and post-dowel space
      preparation in each experimental group (P>0.05). In pre-post space preparation,
      significant difference was found between group A and group B, group B and group C
      (P<0.05). In post-dowel space preparation, difference was found between group A
      and group B.Group A had the lowest microleakage (4.328+/-2.020)x10(-3)microl x
      kPa(-1) x min(-1). CONCLUSIONS: The post space preparation do not effect the
      sealability of three root canal sealers. The sealability of canals filled with AH
      Plus are different when filled with different filling methods. Normal temperature
      flow gutta-percha single-corn technique with GuttaFlow gains the best
      sealability.

PMID- 20143030
TI  - [Effect of three types of cements and the timing of tooth preparation on the
      retention of cast posts and cores].
AB  - PURPOSE: The aim of this laboratory experiment was to study the effects of the
      timing of tooth preparation after cemented with three kinds of cements on the
      retention of cast posts and cores. METHODS: Sixty extracted intact mandibular
      human premolars with single root were involved in this study. Cast posts and
      cores were fabricated for each tooth and randomly divided into three groups of 20
      specimens each,cemented with three different cements: zinc phosphate cement
      (ZPC), zinc poly crylate cement (ZPCC)and glass-ionomer cement (GIC). Three
      groups were then randomly divided into four subgroups of 5 specimens each which
      were subjected to preparation of their cores at 10 minutes, 30 minutes, 1 hour
      and 24 hours after cement. After one week of cement, each post core system was
      subjected to an axially directed removal force using an universal testing machine
      at a speed of 1 mm /min. Difference among the three groups was determined using
      SPSS11.5 software package. The data was analyzed by one-way variance analysis and
      Student-Newman-Keuls (SNK) pairwise multiple comparisons. RESULTS: Retention of
      cast posts significantly increased as the timing of tooth preparation increased
      for both groups, the value of group D (24h) was significantly greater than the
      other three groups, P<0.05; the posts cemented with ZPC provided significantly
      greater retention, ZPC>ZPCC, P<0.01; ZPC>GIC, P<0.01; GIC>ZPCC, P<0.05.
      CONCLUSIONS: The timing of tooth preparation has a significant effect on the
      retention of cast posts and cores; tooth preparation at 24 hours after
      cementation is suggested. And in the same timing of tooth preparation, the posts
      cemented with ZPC provided significantly greater tensile resistance, ZPC is still
      a high-performance cement to cement post compared to other cements.

PMID- 20143031
TI  - [Analysis of the curriculum of the University of California, Los Angeles School
      of Dentistry].
AB  - By comparative analysis of the curriculum of the University of California, Los
      Angeles (UCLA) School of Dentistry with Shandong University College of
      Stomatology, this paper explored what could be used as reference for Chinese
      dental educators. The curriculum characteristics and teaching ways in UCLA was
      analyzed; the dental courses of UCLA were compared with Shandong University,
      fourteen courses opened in UCLA were not opened in Shandong University; eight
      forefront courses selected from the fourteen courses were introduced. The
      analysis showed that in certain degree the curriculum characteristics and
      teaching ways of UCLA could be used for reference and fourteen forefront courses
      were also necessary. It's suggested to increase the proportion of dental courses,
      increase hours for experiments, combine theories and experiments tightly and
      gradually open forefront courses such as Clinical Applications of Dental
      Morphology, Esthetic Dentistry, Geriatric Dentistry, Hospital Dentistry, Health
      Policy Issues, Methods in Evidence-based Dentistry, Introduction to Behavioral
      Science, Patient Management and so on within domestic universities.

PMID- 20143032
TI  - [Research progress of flared roots reinforced with resins and methods of
      evaluation].
AB  - With the development of root canal therapy, and prosthodontic materials,
      techniques as well, the restoration of residual roots has made great progress.
      However, the restoration of endodontically treated teeth with excessive loss of
      mineralized tissues still presents a challenge to dentists. Prognosis is
      comparatively poor if flared roots are restored by conventional methods. Many
      scholars have devoted themselves to the researches on how to reinforce the
      compromised root to increase the fracture resistance. The newly research progress
      of methods, results and evaluations for flared roots reinforcement were reviewed
      in this paper.

PMID- 20143033
TI  - [The crown inclination of the teeth and its clinical value].
AB  - The crown inclination, representing an angle formed by the clinical crown axis
      and a line which bears 90 degrees to the occlusal plane, reflects the
      labiolingual or buccolingual inclination of the long axis of the crown. The crown
      inclination is related to the races. And it is compensated by different vertical
      or sagittal jaw relationships. It plays an important role in fine occlusal
      relationship and achieving functional, artistic and stable treatment goal. The
      torque design of the straight wire bracket is based on the normal crown
      inclination. There is much discrepancy in the torque design of the different
      straight wire bracket because of the different race and philosophy. This review
      gave a brief introduction of the influential factors, the clinical meaning of the
      crown inclination and the torque design of the different bracket system.

PMID- 20143034
TI  - [Self-healing Langerhans cell histiocytosis in a child: case report and
      literature review].
AB  - Langerhans cell histiocytosis is an entity of Langerhans cell with its proto-cell
      proliferating locally or disseminatively. Children below 3 years old always
      present an acute disseminated type. The responsible cell involves in multiple
      systems and the viscera, so it often undergoes a poor prognosis. Without medical
      interference, the natural course of the disease may be within 6 months. But in
      this paper, a 19-month-old child was reported who was diagnosed Langerhans cell
      histiocytosis by biopsy and self-healed without treatment. After over 9 years of
      follow-up, no recurrence was found.

PMID- 20143035
TI  - [Calcifying epithelioma in the neck: report of one case].
AB  - Calcifying epithelioma is one kind of benign tumour,which rarely happens in the
      neck. The clinical diagnosis of calcifying epithelioma is difficult and
      misdiagnosis is common. This paper reported one case of calcifying epithelioma in
      the neck, and discussed its clinical features and therapy based on literature
      review.

PMID- 20143036
TI  - [Foreign stone retaining in right post-maxillary molar area for 10 years causing
      limitation of mouth opening: report of one case].
AB  - It is common to see a foreign body retained in the soft tissues of oral and
      maxillofacial region. However, a foreign body retaining in oral and maxillofacial
      region for more than 10 years and resulting in limitation of mouth opening is
      rare. This paper reported a 52-year-old man, who had limitation of mouth opening
      for more than 1 year caused by a stone retaining in right post-maxillary molar
      area for 10 years. The clinical manifestations, X-ray and CT findings, treatment
      result were summarized. This case suggested that oral and maxillofacial surgeons
      should ask the patients medical history in details. With other imaging
      examinations, surgeons could make definite diagnosis of oral and maxillofacial
      foreign body.

PMID- 20143037
TI  - [Double root canal of all mandibular incisors: report of one case and review of
      the literature].
AB  - Mandibular incisors are the smallest human permanent teeth with complex root
      canals. Double root canal, lateral branch of root canal, apical ramification or
      apical furcation usually happen, which make the clinical therapy more difficult.
      In this paper, a case of mandibular incisors with double root canals was
      reported, the root canal type and its incidence were discussed.

PMID- 20143038
TI  - Eating and shift work - effects on habits, metabolism and performance.
AB  - Compared to individuals who work during the day, shift workers are at higher risk
      of a range of metabolic disorders and diseases (eg, obesity, cardiovascular
      disease, peptic ulcers, gastrointestinal problems, failure to control blood sugar
      levels, and metabolic syndrome). At least some of these complaints may be linked
      to the quality of the diet and irregular timing of eating, however other factors
      that affect metabolism are likely to play a part, including psychosocial stress,
      disrupted circadian rhythms, sleep debt, physical inactivity, and insufficient
      time for rest and revitalization. In this overview, we examine studies on food
      and nutrition among shift workers [ie, dietary assessment (designs, methods,
      variables) and the factors that might influence eating habits and metabolic
      parameters]. The discussion focuses on the quality of existing dietary assessment
      data, nutritional status parameters (particularly in obesity), the effect of
      circadian disruptions, and the possible implications for performance at work. We
      conclude with some dietary guidelines as a basis for managing the nutrition of
      shift workers.

PMID- 20143039
TI  - Communally breeding bats use physiological and behavioural adjustments to
      optimise daily energy expenditure.
AB  - Small endotherms must change roosting and thermoregulatory behaviour in response
      to changes in ambient conditions if they are to achieve positive energy balance.
      In social species, for example many bats, energy expenditure is influenced by
      environmental conditions, such as ambient temperature, and also by social
      thermoregulation. Direct measurements of daily fluctuations in metabolic rates in
      response to ambient and behavioural variables in the field have not been
      technologically feasible until recently. During different reproductive periods,
      we investigated the relationships between ambient temperature, group size and
      energy expenditure in wild maternity colonies of Bechstein's bats (Myotis
      bechsteinii). Bats used behavioural and physiological adjustments to regulate
      energy expenditure. Whether bats maintained normothermia or used torpor, the
      number of bats in the roosts as well changed with reproductive status and ambient
      temperature. During pregnancy and lactation, bats remained mostly normothermic
      and daily group sizes were relatively large, presumably to participate in the
      energetic benefits of social thermoregulation. In contrast, smaller groups were
      formed on days when bats used torpor, which occurred mostly during the post
      lactation period. Thus, we were able to demonstrate on wild animals under natural
      conditions the significance of behavioural and physiological flexibility for
      optimal thermoregulatory behaviour in small endotherms.

PMID- 20143040
TI  - Constraints on energetic particles in the Fleischmann-Pons experiment.
AB  - In recent Fleischmann-Pons experiments carried out by different groups, a thermal
      signal is seen indicative of excess energy production of a magnitude much greater
      than can be accounted for by chemistry. Correlated with the excess heat appears
      to be (4)He, with the associated energy near 24 MeV per helium atom. In nuclear
      reactions, the energy produced is expressed through the kinetic energy of the
      products; hence, it would be natural to assume that some of the reaction energy
      ends up as kinetic energy of the (4)He nucleus. Depending on the energy that the
      helium nucleus is born with, it will result in radiation (such as neutrons or x
      rays) that can be seen outside of the cell. We have computed estimates of the
      expected neutron and x-ray emission as a function of helium energy and compared
      the results with upper limits taken from experiments. Experimental results with
      upper limits of neutron emission between 0.008 and 0.8 n/J are found to
      correspond to upper limits in alpha energy between 6.2 and 20.2 keV.

PMID- 20143041
TI  - Integration of genome and phenotypic scanning gives evidence of genetic structure
      in Mesoamerican common bean (Phaseolus vulgaris L.) landraces from the southwest
      of Europe.
AB  - Southwestern Europe has been considered as a secondary centre of genetic
      diversity for the common bean. The dispersal of domesticated materials from their
      centres of origin provides an experimental system that reveals how human
      selection during cultivation and adaptation to novel environments affects the
      genetic composition. In this paper, our goal was to elucidate how distinct events
      could modify the structure and level of genetic diversity in the common bean. The
      genome-wide genetic composition was analysed at 42 microsatellite loci in
      individuals of 22 landraces of domesticated common bean from the Mesoamerican
      gene pool. The accessions were also characterised for phaseolin seed protein and
      for nine allozyme polymorphisms and phenotypic traits. One of this study's
      important findings was the complementary information obtained from all the
      polymorphisms examined. Most of the markers found to be potentially under the
      influence of selection were located in the proximity of previously mapped genes
      and quantitative trait loci (QTLs) related to important agronomic traits, which
      indicates that population genomics approaches are very efficient in detecting
      QTLs. As it was revealed by outlier simple sequence repeats, loci analysis with
      STRUCTURE software and multivariate analysis of phenotypic data, the landraces
      were grouped into three clusters according to seed size and shape, vegetative
      growth habit and genetic resistance. A total of 151 alleles were detected with an
      average of 4 alleles per locus and an average polymorphism information content of
      0.31. Using a model-based approach, on the basis of neutral markers implemented
      in the software STRUCTURE, three clusters were inferred, which were in good
      agreement with multivariate analysis. Geographic and genetic distances were
      congruent with the exception of a few putative hybrids identified in this study,
      suggesting a predominant effect of isolation by distance. Genomic scans using
      both markers linked to genes affected by selection (outlier) and neutral markers
      showed advantages relative to other approaches, since they help to create a more
      complete picture of how adaptation to environmental conditions has sculpted the
      common bean genomes in southern Europe. The use of outlier loci also gives a clue
      about what selective forces gave rise to the actual phenotypes of the analysed
      landraces.

PMID- 20143042
TI  - SRAP polymorphisms associated with superior freezing tolerance in alfalfa
      (Medicago sativa spp. sativa).
AB  - Sequence-related amplified polymorphism (SRAP) analysis was used to uncover
      genetic polymorphisms among alfalfa populations recurrently selected for superior
      tolerance to freezing (TF populations). Bulk DNA samples (45 plants/bulk) from
      each of the cultivar Apica (ATF0), and populations ATF2, ATF4, ATF5, and ATF6
      were evaluated with 42 different SRAP primer pairs. Several polymorphisms that
      progressively intensified or decreased with the number of recurrent cycles were
      identified. Four positive polymorphisms (F10-R14, Me4-R8, F10-R8 and F11-R9)
      that, respectively, yielded 540-, 359-, 213-, and 180-bp fragments were selected
      for further analysis. SRAP amplifications with genotypes within ATF populations
      confirmed that the polymorphisms identified with bulk DNA samples were reflecting
      changes in the frequency of their occurrence in response to selection. In
      addition, the number of genotypes cumulating multiple polymorphisms markedly
      increased in response to recurrent selection. Independent segregation of the four
      SRAP polymorphisms suggests location at unlinked loci. Homology search gave
      matches with BAC clones from syntenic Medicago truncatula for the four SRAP
      fragments. Analysis of the relationship with low temperature tolerance showed
      that multiple SRAP polymorphisms are more frequent in genotypes that maintain
      superior regrowth after freezing. These results show that SRAP analysis of bulk
      DNA samples from recurrent selections is an effective approach for the
      identification of genetic polymorphisms associated with quantitative traits in
      allogamous species. These polymorphisms could be useful tools for indirect
      selection of freezing tolerance in alfalfa.

PMID- 20143043
TI  - Cloning and genetic diversity analysis of a new P5CS gene from common bean
      (Phaseolus vulgaris L.).
AB  - Delta(1)-pyrroline-5-carboxylate synthetase (P5CS) is the rate-limiting enzyme
      involved in the biosynthesis of proline in plants. By the 3' rapid amplification
      of cDNA ends (3'-RACE) approach, a 2,246-bp cDNA sequence was obtained from
      common bean (Phaseolus vulgaris L.), denominated PvP5CS2 differing from another
      P5CS gene that we cloned previously from common bean (PvP5CS). The predicted
      amino acid sequence of PvP5CS2 has an overall 93.2% identity GmP5CS (Glycine max
      L. P5CS). However, PvP5CS2 shows only 83.7% identity in amino acid sequence to
      PvP5CS, suggesting PvP5CS2 represents a homolog of the soybean P5CS gene.
      Abundant indel (insertion and deletion events) and SNP (single nucleotide
      polymorphisms) were found in the cloned PvP5CS2 genome sequence when comparing 24
      cultivated and 3 wild common bean accessions and these in turn reflected aspects
      of common bean evolution. Sequence alignment showed that genotypes from the same
      gene pool had similar nucleotide variation, while genotypes from different gene
      pools had distinctly different nucleotide variation for PvP5CS2. Furthermore,
      diversity along the gene sequence was not evenly distributed, being low in the
      glutamic-g-semialdehyde dehydrogenase catalyzing region, moderate in the Glu-5
      kinase catalyzing region and high in the intervening region. Neutrality tests
      showed that PvP5CS2 was a conserved gene undergoing negative selection. A new
      marker (Pv97) was developed for genetic mapping of PvP5CS2 based on an indel
      between DOR364 and G19833 sequences and the gene was located between markers
      Bng126 and BMd045 on chromosome b01. The relationship of PvP5CS2 and a previously
      cloned pyrroline-5-carboxylate synthetase gene as well as the implications of
      this work on selecting for drought tolerance in common bean are discussed.

PMID- 20143044
TI  - Prospective association between fasting NEFA and type 2 diabetes: impact of post
      load glucose.
AB  - AIMS/HYPOTHESIS: Elevated fasting NEFAs are thought to promote type 2 diabetes.
      Three prospective studies support this concept, showing increased diabetes risk
      associated with fasting NEFA. However, these prospective associations may be
      confounded by strong cross-sectional correlations between fasting NEFA and
      metabolic predictors of diabetes. To examine this assumption, we used cohort data
      from the Insulin Resistance Atherosclerosis Study (IRAS). METHODS: Within the
      IRAS cohort (n = 902, 145 incident cases), we examined nine metabolic variables
      for their confounding effect on the fasting NEFA-diabetes association: 2 h
      glucose; fasting plasma glucose; body mass index; waist circumference; waist-to
      hip ratio; weight; insulin sensitivity (S (I)); fasting insulin; and acute
      insulin response. We compared odds ratios for fasting NEFA (log( e ) transformed
      and adjusted for age, sex, ethnicity and clinic) before and after inclusion of
      each metabolic variable into a logistic regression model. RESULTS: Three
      variables (2 h glucose, BMI and S (I)) cross-sectionally correlated with fasting
      NEFA (r > or = 0.1, p < 0.05). Unadjusted for metabolic predictors, fasting NEFA
      levels were positively associated with diabetes risk: OR 1.37 (95% CI 0.87-2.15)
      per unit on a log scale. All metabolic variables except AIR showed confounding.
      Inclusion of 2 h glucose reversed the positive association (OR 0.50 [95% CI 0.30
      0.82]), whereas other predictors reduced the association to the null. The final
      model included the variables correlated with baseline fasting NEFA (2 h glucose,
      BMI and S (I)) and the demographic variables resulting in OR 0.47 (95% CI 0.27
      0.81). CONCLUSIONS/INTERPRETATION: Our results indicate that 2 h glucose strongly
      confounds the prospective association between fasting NEFA and diabetes;
      carefully adjusted fasting NEFA levels are inversely associated with diabetes
      risk.

PMID- 20143045
TI  - Displaced avulsion fracture of medial meniscus posterior horn through the
      intercondylar notch in the patient without combined ligamentous injuries.
AB  - Avulsion fractures of the posterior horn of the medial meniscus are uncommon and
      must be differentiated from a loose body. The authors present a displaced
      avulsion fracture of the medial meniscus posterior horn through the intercondylar
      notch into the anteromedial compartment of the knee, which was treated by
      arthroscopic reduction and internal fixation using pull-out suture technique.

PMID- 20143046
TI  - Symptomatic torn discoid lateral meniscus in adults.
AB  - The purposes of this study were to report degenerative changes that coexist with
      a symptomatic torn discoid lateral meniscus in adults and to analyze the factors
      associated with the accompanied degenerative changes. From 1997 to 2008, 329
      knees in the 305 patients were included. Associations between the status of the
      meniscus and the coexisting degenerative changes on the images and the
      arthroscopic findings were statistically analyzed. Marginal osteophyte was seen
      on conventional radiography in 118 patients (36%). Ninety patients (27%) had
      arthroscopically confirmed chondral lesion. Age, duration of symptoms, the type
      of meniscus, the type of tear and the magnetic resonance image classification
      were associated with the formation of the marginal osteophyte and chondral lesion
      on univariate analysis (P < 0.05). After conducting multivariate analysis, the
      type of tear and magnetic resonance image classification had a statistically
      significant association with the severity of marginal osteophyte and chondral
      lesion (P < 0.05).

PMID- 20143047
TI  - The effects of drug and behavior therapy on urgency and voiding frequency.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to examine the
      effects of drug therapy alone and combined with behavioral therapy on urgency and
      24-voiding frequency in women with urge-predominant incontinence and to identify
      predictors of change. METHODS: A planned analysis of data from a multi-site,
      randomized, controlled trial (N = 307). Bladder diaries were used to document
      voids, incontinence, and urgency severity. RESULTS: Urgency scores decreased
      significantly within both treatment groups, but changes did not differ between
      groups (p = 0.30). Improvement in urgency was associated with greater baseline
      urgency (p < 0.0001) and black ethnicity (p = 0.03). Voiding frequency increased
      with drug alone and decreased slightly with combined therapy (p = 0.009), and
      improvement was associated with combined treatment (p < 0.0001), higher baseline
      frequency (p < 0.0001), and lower baseline incontinence episode frequency (p =
      0.001). CONCLUSIONS: Although combined drug and behavioral therapy does not
      appear to improve urgency more than drug alone, it resulted in better outcomes on
      voiding frequency.

PMID- 20143048
TI  - Interposition grafts for rectovaginal fistula repair in the New Zealand white
      rabbit.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to use an animal model to study
      different types of interposition grafts for rectovaginal fistula repair. METHODS:
      Twelve New Zealand white rabbits underwent surgical creation of a rectovaginal
      fistula, followed by repair. Four repair techniques were studied; three with
      interposition grafts and one control group without a graft. Animals were
      euthanized at 4-week intervals and underwent gross and histologic analysis.
      RESULTS: The mean rectovaginal wall thickness was greatest in the control group
      (5.6 mm) and thinnest in the autologous rectus fascia (4.2 mm) and porcine small
      intestine submucosa (5.1 mm) groups. The polypropylene graft had a mean thickness
      of 5.4 mm and elicited a strong, protracted inflammatory response. All fistulas
      were successfully closed except one porcine small intestine submucosa repair.
      CONCLUSIONS: There is no benefit from interposition graft use for rectovaginal
      fistula repair in our New Zealand white rabbit model.

PMID- 20143049
TI  - Relationship between endoplasmic reticulum- and Golgi-associated calcium
      homeostasis and 4-NQO-induced DNA repair in Saccharomyces cerevisiae.
AB  - Calcium (Ca(2+)) is an important ion that is necessary for the activation of
      different DNA repair mechanisms. However, the mechanism by which DNA repair and
      Ca(2+) homeostasis cooperate remains unclear. We undertook a systems biology
      approach to verify the relationship between proteins associated with Ca(2+)
      homeostasis and DNA repair for Saccharomyces cerevisiae. Our data indicate that
      Pmr1p, a Ca(2+) transporter of Golgi complex, interacts with Cod1p, which
      regulates Ca(2+) levels in the endoplasmic reticulum (ER), and with Rad4p, which
      is a nucleotide excision repair (NER) protein. This information was used to
      construct single and double mutants defective for Pmr1p, Cod1p, and Rad4p
      followed by cytotoxic, cytostatic, and cell cycle arrest analyses after cell
      exposure to different concentrations of 4-nitroquinoline 1-oxide (4-NQO). The
      results indicated that cod1Delta, cod1Deltarad4Delta, and cod1Deltapmr1Delta
      strains have an elevated sensitivity to 4-NQO when compared to its wild-type (WT)
      strain. Moreover, both cod1Deltapmr1Delta and cod1Deltarad4Delta strains have a
      strong arrest at G(2)/M phases of cell cycle after 4-NQO treatment, while
      pmr1Deltarad4Delta have a similar sensitivity and cell cycle arrest profile when
      compared to rad4Delta after 4-NQO exposure. Taken together, our results indicate
      that deletion in Golgi- and ER-associated Ca(2+) transporters affect the repair
      of 4-NQO-induced DNA damage.

PMID- 20143050
TI  - Coordination of grasping and walking in Parkinson's disease.
AB  - Studies on grasp control underlying manual dexterity in people with Parkinson
      disease (PD) suggest that anticipatory grasp control is mainly unaffected during
      discrete tasks using simple two-digit grasp. Nevertheless, impaired hand function
      during daily activities is one of the most disabling symptoms of PD. As many
      daily grasping activities occur during functional movements involving the whole
      body, impairments in anticipatory grasp control might emerge during a continuous
      dynamic task such as object transport during walking. In this case, grasp control
      must be coordinated along with multiple body segments. The present study
      investigated the effect of PD on anticipatory grasp control and intersegmental
      coordination during walking with a hand-held object. Nine individuals with
      idiopathic PD (tested OFF and ON medication) and nine healthy age-matched
      controls carried a grip instrument between their right thumb and index finger
      during self-paced and fast walking. Although the amplitude of grip forces was
      higher in standing and walking for subjects with PD, both subjects with PD and
      control subjects coupled grip and inertial force changes in an anticipatory
      fashion while walking. However, gait-induced motions of the object relative to
      that of the trunk (i.e., dampening) was reduced in subjects with PD. Medication
      increased the dampening in all subjects with PD. We suggest that these
      differences are associated with impairments in intersegmental coordination.

PMID- 20143051
TI  - L-dopa induces under-damped visually guided motor responses in Parkinson's
      disease.
AB  - Parkinson's disease preferentially affects internally generated movements, e.g.,
      movements recalled from memory, while externally cued movements are relatively
      preserved. However, L-dopa may have effects on visually guided movements as well
      as error-related processing. Fourteen Parkinson's disease (PD) subjects (on and
      off L-dopa medication) as well as ten normal controls performed a tracking task
      using a joystick. During discrete 30 s blocks, the visual feedback of the actual
      tracking errors were attenuated, amplified or unaltered. Second order dynamical
      system models, with the desired trajectory as the input and the actual motor
      performance as the output, were used to characterize the motor performance by the
      each subject under each condition. Although the overall root-mean-square tracking
      error did not significantly differ between groups, the nature of the motor
      performance differed significantly across groups. A clear dissociation was made
      between manipulations of error feedback--which altered the natural frequency of
      the models--and the effects of L-dopa, which affected damping. Compared to normal
      controls, PD subjects were significantly overdamped before medication and
      underdamped after medication. We interpret our results as being suggestive of L: 
      dopa normalization of compensatory overactive cerebellar activity in PD.

PMID- 20143052
TI  - Carriers of the UGT1A4 142T>G gene variant are predisposed to reduced olanzapine
      exposure--an impact similar to male gender or smoking in schizophrenic patients.
AB  - PURPOSE: The impact of the UGT1A4, CYP1A2, and MDR1 genetic variants on
      olanzapine plasma levels, in relation to those of other individual factors, such
      as gender, smoking status, body weight, and age, was investigated in patients
      with schizophrenia. METHODS: A total of 121 patients were recruited from
      psychosis-specialized outpatient departments in Stockholm County. Olanzapine
      plasma concentrations were determined by high-performance liquid chromatography.
      Genotyping was carried out by PCR-restriction fragment length polymorphism or
      minisequencing, and haplotypes were analyzed using specialized computer software
      on population genetics. Multiple regression analysis was performed to investigate
      the combined effect of patient characteristics and genotypes/haplotypes on daily
      dose-corrected plasma concentrations of olanzapine. RESULTS: In addition to , the
      results indicate that inter-patient differences in olanzapine exposure were
      explained by the known factor of time of sampling from last dose intake and by
      the following individual factors in order of relative impact: (1) male gender,
      (2) carrier of the UGT1A4 142T>G single nucleotide polymorphism (SNP), and (3)
      smoking. Each of these three factors predicted a decrease in daily dose-corrected
      plasma concentrations of 35, 25, and 21%, respectively. In contrast, age, body
      weight, and MDR1 or CYP1A2 haplotype did not have a significant impact.
      CONCLUSIONS: At 12 h after dose intake, the regression model predicted a 5.1-fold
      higher olanzapine plasma level in a non-smoking female patient who did not carry
      the UGT1A4 142T>G SNP compared to a smoking man treated with the same dose but
      heterozygous for UGT1A4 142T>G SNP. Whether these combined genetic and
      environmental factors influence the risk of therapeutic failure remains to be
      established.

PMID- 20143053
TI  - Occurrence and distribution of metals in mussels from the Cantabrian coast.
AB  - From February 2004 to April 2006, the concentrations of more than 10 metals in
      mussels (Mytilus galloprovincialis) were measured in 10 stations from Galicia to
      the Basque Country in 8 different times of sampling. The mean highest
      concentrations are found for Zn [226.8 microg/g, dry weight (d.w.)] followed by
      Mn, As, Cu, and Co (between 10 and 25 microg/g d.w.). Lower mean concentrations
      are found for Se, Cr, Pb, V, and Ni (between 2 and 8 microg/g d.w.) and the
      lowest are for Cd, Sn, Hg, and Sb (between 0.05 and 1 microg/g d.w.). Among the
      statistical treatments used, the factor analysis showed a clustering of the
      mussels according to the geographical location. In addition, the temporal trend
      of the metal concentrations was studied by means of the Mann-Kendall test. In
      this sense, some stations showed a decreasing trend in the accumulation of the
      metallic content. However, there were some local pollution events that could be
      explained as a consequence of anthropogenic activities. Finally, the effects of
      the oil spill from the Prestige are discussed based on the experimental Ni/V
      ratio values obtained from this work and those of the original oil.

PMID- 20143054
TI  - Myocardial performance in asphyxiated full-term infants assessed by Doppler
      tissue imaging.
AB  - The aim of this study was to assess myocardial performance of full-term infants
      with perinatal asphyxia using Doppler tissue imaging (DTI) and to correlate it
      with serum cardiac troponin T (cTnT) concentrations. Twenty-five asphyxiated and
      20 nonasphyxiated term infants were investigated. Serum cTnT concentrations were
      measured between 12 and 24 h of life. Conventional two-dimensional Doppler
      echocardiography and DTI were done during the first 72 h of life. Right
      ventricular (RV) and left ventricular (LV) Tei indexes were significantly higher
      in asphyxiated neonates (mean +/- SD: 0.45 +/- 0.05 vs. 0.28 +/- 0.05, P < 0.001
      and 0.51 +/- 0.04 vs. 0.38 +/- 0.04, P < 0.001, respectively). Mitral and
      tricuspid systolic (Sm) velocities were significantly lower in asphyxiated
      neonates (mean +/- SD: 5.06 +/- 0.89 vs. 6.89 +/- 0.94 cm/s, P < 0.001 and 5.78
      +/- 0.58 vs. 6.69 +/- 0.87 cm/s, P < 0.001, respectively). cTnT concentrations
      were significantly higher in asphyxiated neonates [median (range): 0.17 (0.05
      0.23) vs. 0.03 (0-0.07) microg/l, P < 0.001)], and they correlated positively
      with the LV Tei index (r = 0.67, P < 0.001) and the RV Tei index (r = 0.68, P <
      0.001) and negatively with the mitral systolic (Sm) velocity (r = -0.68, P <
      0.001) and tricuspid systolic (Sm) velocity (r = -0.41, P = 0.01). A higher cTnT
      was a significant predictor of mortality, whereas fractional shortening (FS) and
      DTI measurements did not show any significant predictive value. The DTI technique
      appears to be more sensitive than conventional echocardiography in the early
      detection of myocardial dysfunction induced by perinatal asphyxia in full-term
      infants.

PMID- 20143055
TI  - Clinical experience of chest pain in adults with congenital heart disease in a
      single tertiary center.
AB  - The aim of this study was to investigate clinical manifestation and causes of
      chest pain in adults with congenital heart disease. Of 966 patients in our Adult
      Congenital Heart Clinic, 50 patients had cyanosis (cyanosis [+]), and 916
      patients did not have cyanosis (cyanosis [-]). Fifty-four patients (16 male and
      38 female) with a history of chest pain requiring medical care were selected: 33
      were in the cyanosis (+) group, and 21 were in the cyanosis (-) group. Medical
      records were reviewed. The causes of chest pain were (no. cyanosis [+], no.
      cyanosis [-], respectively) as follows: idiopathic (n = 19, n = 10), pulmonary
      hemorrhage (n = 6, n = 0), pulmonary tuberculosis (n = 2, n = 0), pulmonary
      thromboembolism (n = 4, n = 0), localized musculoskeletal (n = 1, n = 1),
      myocardial ischemia (n = 1, n = 1), and arrhythmia (n = 2, n = 9). Patients with
      cyanosis had much higher frequency of chest pain compared with patients without
      cyanosis (33 of 50 vs. 21 of 916, p < 0.0001). Chest pain in adults with
      congenital heart disease has diverse causes. Meticulous evaluation of chest pain
      in adults with congenital heart disease is required to differentiate correctable
      causes from idiopathic or incurable ones.

PMID- 20143056
TI  - Successful pulmonary embolectomy in a 4-year-old girl with antithrombin III
      deficiency.
AB  - We report the case of a 4-year-old girl, successfully treated by surgical
      pulmonary embolectomy for acute massive pulmonary embolism. She was known to have
      a congenital antithrombin III deficiency diagnosed after a familial history of
      thromboembolic events. Surgical embolectomy may be considered as a treatment
      option in selected patient with anatomically extensive pulmonary embolism.

PMID- 20143057
TI  - Persistent fifth aortic arch with coarctation.

PMID- 20143058
TI  - Right ventricular dysplasia with massive thromboemboli in tuberous sclerosis
      complex.
AB  - A 12-year-old boy visited the emergency room for severe dyspnea. He was diagnosed
      with tuberous sclerosis at 5 years of age, and right ventricular dysplasia was
      detected at 11 years of age. Thromboemboli in right ventricle and bilateral
      pulmonary arteries were confirmed with two-dimensional echocardiography and
      computed tomography. We report the case of a patient with tuberous sclerosis who
      presented with huge thrombi in a dysplastic right ventricle and massive bilateral
      pulmonary thromboemboli without evidence of a cardiac tumor.

PMID- 20143059
TI  - Nail-patella syndrome (Fong disease).

PMID- 20143060
TI  - Lipoprotein lipase deficiency with visceral xanthomas.
AB  - Lipoprotein lipase deficiency (LLD) is a rare metabolic disorder that typically
      presents with skin xanthomas and pancreatitis in childhood. We report a case of
      LLD in an infant who presented with jaundice caused by a pancreatic head mass.
      Abdominal imaging also incidentally revealed hyperechoic renal masses caused by
      renal xanthomas. This appearance of the multiple abdominal masses makes this a
      unique infantile presentation of LLD.

PMID- 20143061
TI  - Tuberculous broncho-oesophageal fistula: images demonstrating the pathogenesis.

PMID- 20143063
TI  - Percutaneous vertebroplasty for intravertebral cleft: analysis of therapeutic
      effects and outcome predictors.
AB  - OBJECTIVE: To investigate the short-term therapeutic effect of percutaneous
      vertebroplasty (PVP) for intravertebral cleft (IVC) and to analyze possible
      outcome predictors. MATERIALS AND METHODS: After retrospective review of spot
      radiographs during PVP, 23 patients were included in this study. Age, sex,
      symptom duration, functional status, injected cement volume, and type of approach
      were evaluated using patients' medical and operative records. The following
      factors were analyzed on radiographs, MRI, dual bone densitometry, spot
      radiographs during PVP, and CT: anatomical location of the fracture, bone mineral
      density, morphology of the fracture, IVC morphology, presence of surrounding non
      enhanced area and bone marrow edema, degeneration of adjacent discs, co-existing
      old compression fractures, patterns of cement opacification, pre-procedural
      kyphosis, and post-procedural kyphosis correction. Effectiveness was defined as a
      much-improved state or no pain after 1 week, 1 month, and 2 months. Statistical
      analyses were conducted to evaluate the relationship between those factors and
      therapeutic outcome using Fisher's exact test, Chi-squared test, and the Mann
      Whitney U test. RESULTS: Percutaneous vertebroplasty of IVC was effective in 16
      out of 23 (69.6%) patients after 1 week and 1 month and 15 out of 23 (65.2%)
      patients after 2 months. Post-procedural kyphosis correction >or=5 and poor
      functional status (full dependency) were more common in the ineffective group
      after 1 week and 2 months respectively (P = 0.047, P = 0.02). Kyphotic correction
      >or=5 was related to pre-procedural kyphosis >or=15 (P = 0.018). Functional
      status was related to subsequent fracture (P = 0.005). Other factors were not
      statistically significant (P > 0.05). CONCLUSIONS: Percutaneous vertebroplasty on
      osteoporotic vertebral compression fractures (VCF) with IVC was effective in only
      about 69.6% of patients after the first week and month and in 65.2% of patients
      after 2 months. Post-procedural kyphosis correction >or=5 was associated with
      poor outcomes after the first week. Two months after PVP, the functional status
      was more important because of the development of subsequent fractures.

PMID- 20143064
TI  - Visual assessment of [(11)C]PIB PET in patients with cognitive impairment.
AB  - PURPOSE: The aim of this study was to evaluate the visual assessment of positron
      emission tomography images of N-[methyl-11C]2-(4'-methylaminophenyl)-6
      hydroxybenzothiazole ([11C]PIB) in a patient population with mild to moderate
      memory impairment or dementia. METHODS: We compared the visual ratings of two
      readers using kappa statistics and correlated the results of visual and
      quantitative region of interest (ROI) analyses. The one reader had good
      experience in evaluating PIB images and the other had little previous experience.
      The sensitivity and specificity of the visual assessment was determined using
      quantitative data from 18 healthy controls previously examined: [11C]PIB uptake
      was considered as abnormal if it was more than 2 SD above the mean of the healthy
      subjects. RESULTS: The evaluation of visual classification as "normal" or
      "abnormal" showed good interobserver agreement (kappa = 0.90). There was a clear
      correlation between visual and quantitative analysis (r = 0.47-0.79, p < 0.001).
      The most difficult visually assessed brain area was the putamen (kappa = 0.11;
      correlation with quantitative analysis: reader A r = 0.22; reader B r = 0.60).
      CONCLUSION: Our study shows that visual evaluation of [(11)C]PIB images conforms
      with quantitative analyses also in a clinical patient population supporting the
      feasibility of visual evaluation in clinical settings.

PMID- 20143065
TI  - The influence of nutrients and physical habitat in regulating algal biomass in
      agricultural streams.
AB  - This study examined the relative influence of nutrients (nitrogen and phosphorus)
      and habitat on algal biomass in five agricultural regions of the United States.
      Sites were selected to capture a range of nutrient conditions, with 136 sites
      distributed over five study areas. Samples were collected in either 2003 or 2004,
      and analyzed for nutrients (nitrogen and phosphorous) and algal biomass
      (chlorophyll a). Chlorophyll a was measured in three types of samples, fine
      grained benthic material (CHL(FG)), coarse-grained stable substrate as in rock or
      wood (CHL(CG)), and water column (CHL(S)). Stream and riparian habitat were
      characterized at each site. TP ranged from 0.004-2.69 mg/l and TN from 0.15-21.5
      mg/l, with TN concentrations highest in Nebraska and Indiana streams and TP
      highest in Nebraska. Benthic algal biomass ranged from 0.47-615 mg/m(2), with
      higher values generally associated with coarse-grained substrate. Seston
      chlorophyll ranged from 0.2-73.1 microg/l, with highest concentrations in
      Nebraska. Regression models were developed to predict algal biomass as a function
      of TP and/or TN. Seven models were statistically significant, six for TP and one
      for TN; r(2) values ranged from 0.03 to 0.44. No significant regression models
      could be developed for the two study areas in the Midwest. Model performance
      increased when stream habitat variables were incorporated, with 12 significant
      models and an increase in the r(2) values (0.16-0.54). Water temperature and
      percent riparian canopy cover were the most important physical variables in the
      models. While models that predict algal chlorophyll a as a function of nutrients
      can be useful, model strength is commonly low due to the overriding influence of
      stream habitat. Results from our study are presented in context of a nutrient
      algal biomass conceptual model.

PMID- 20143066
TI  - Posterior retroperitoneoscopic adrenalectomy for clinical and subclinical
      Cushing's syndrome.
AB  - BACKGROUND: Because of co-morbidity, adrenalectomy for adrenal Cushing's syndrome
      may be associated with an increased complication rate and long operating times.
      In the present study we report our experience with the posterior
      retroperitoneoscopic adrenalectomy in a large group of patients with clinical or
      subclinical Cushing's syndrome. PATIENTS AND METHODS: Between July 1994 and June
      2009, 170 patients (17 males, 153 females age 50 +/- 13 years; range: 12-78
      years) affected by Cushing's syndrome underwent operation via posterior
      retroperitoneoscopic access. Patients were divided into two groups, those with
      manifest Cushing's syndrome (mCS) [99 patients: 6 male, 93 female; age 45 +/- 13
      years] and those with subclinical Cushing's syndrome (sCS) [71 patients: 11 male,
      60 female; age: 56 +/- 11 years]. The sCS classification was assumed in cases
      without typical clinical symptoms but with a pathological dexamethasone
      suppression test. Partial adrenalectomy was performed in 35 cases (24 in the mCS
      group and 11 in the sCS-group). RESULTS: Mortality was zero; major complications
      did not occur. The incidence of postoperative minor complications was 5.3%. Mean
      operating time was 58 +/- 36 min (range: 20-230 min) and did not differ between
      mCS and sCS patients (58 versus 59 min; p = ns). Postoperative oral steroids
      supplementation (POSS) was administered in 136 patients (99 mCS, 37 sCS). If POSS
      was started, mean duration of therapy was 12.3 months (mCS) and 10.3 months (sCS)
      [p = 0.08], respectively. After a mean follow-up of 70.9 +/- 46.5 months the cure
      rate was 99.4%. CONCLUSIONS: The posterior retroperitoneoscopic approach is fast
      and safe even in patients with Cushing's syndrome. Partial adrenalectomy
      represents a new option in the treatment of cortisol-producing adenomas.

PMID- 20143067
TI  - Roux-en-Y reconstruction is superior to billroth I reconstruction in reducing
      reflux esophagitis after distal gastrectomy: special relationship with the angle
      of his.
AB  - BACKGROUND: The aim of the present study was to evaluate the relationship between
      the angle of His in Roux-en-Y (RY) or Billroth I (BI) reconstruction and reflux
      esophagitis after distal gastrectomy for gastric cancer. METHODS: Results for 47
      patients undergoing BI reconstruction and 38 patients undergoing RY
      reconstruction were examined retrospectively. The angle of His and the incidence
      of reflux esophagitis were determined, and the quality of life (QOL) was
      evaluated with the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: The
      angle of His was significantly greater in patients who underwent BI compared with
      RY reconstruction, as well as in patients with reflux esophagitis. Scores for
      reflux, diarrhea, and total symptoms on the GSRS were significantly better in the
      RY group than in the BI group. CONCLUSIONS: The angle of His is an important
      determinant of reflux esophagitis following distal gastrectomy. The decreased
      angle of His in patients after RY compared with BI reconstruction may contribute
      significantly to the reduced incidence of reflux esophagitis and improved QOL in
      patients who undergo RY reconstruction.

PMID- 20143068
TI  - Intestinal ascariasis in children.
AB  - BACKGROUND: Ascariasis is a staggering health problem commonly seen in children
      of endemic areas. In the abdomen, ascaris lumbricoides can cause a myriad of
      surgical complications. Intestinal obstruction by ascaris lumbricoides is
      commonly seen in children. Most cases are managed conservatively. The purpose was
      to study the clinical presentation and management of symptomatic intestinal
      ascariasis in children. METHODS: A 3-year study was performed from April 2006 to
      April 2009 of pediatric-age patients who had symptomatic intestinal ascariasis.
      All patients had detailed clinical history, examination, plain X-ray of abdomen,
      and ultrasonography of abdomen. Peroperative findings were recorded in all
      patients who had surgical intervention. RESULTS: This prospective study had 360
      patients. Male to female ratio was 1.37:1. 187 patients (52%) presented within 2
      4 days of duration of illness. Mean +/- standard deviation (SD) age of patients
      was 6.35 +/- 2.25 years. Age group of 4-7 years (80%) was commonest group
      affected. Abdominal pain was a leading symptom in 357 patients (99%) with the
      pain in periumbilical area present in 215 patients (60%). In 227 patients (63%)
      abdominal distension was seen and was the commonest physical finding. Palpable
      worm masses were seen in 129 patients (36%); 81 patients (63%) had palpable worm
      masses in the umbilical quadrant. On X-ray of abdomen, visible worm masses were
      seen in 83 patients (23%). Abdominal sonography showed interloop fluid in 177
      patients (49%) and free fluid in the pelvis of 97 patients (27%). The number of
      patients who were managed conservatively was 281 (78%), and 79 patients (22%) had
      surgical intervention. In patients who had surgical intervention, 39 patients
      (49%) had enterotomy and 7 patients (9%) had kneading of worms. Postoperative
      complications occurred in 33 patients, and an overall mortality of 1% (1 patient)
      was seen. CONCLUSIONS: Ascaridial intestinal obstruction is common in children in
      the Kashmir. Abdominal pain is the leading symptom in intestinal ascariasis.
      Plain X-ray and ultrasonography of the abdomen are used to diagnosis intestinal
      ascariasis. The majority of the patients can be managed conservatively.

PMID- 20143070
TI  - Changes in quality of life after lung surgery in old and young patients: are they
      similar?
AB  - BACKGROUND: The aim of the study was to compare the changes in health-related
      quality of life (QOL) after lung surgery between young and old patients. METHODS:
      We performed a prospective, population-based, cohort study to investigate health
      related QOL before and 6 months after lung surgery. We used the validated
      instrument Short Form-36 (SF-36), to investigate QOL. The main outcome measures
      were fractional change in the SF-36 physical (DeltaPCS%) and mental (DeltaMCS%)
      component summary scores. We also compared the two age groups to age- and sex
      matched reference populations. RESULTS: We included 249 patients: 166 young (<70
      years) and 83 old (> or =70 years) patients. The overall response rate at 6
      months was 84%. There was no significant difference in the primary outcome
      measures between young and old patients (DeltaPCS% -13 vs. -16, p = 0.55;
      DeltaMCS% 9 vs. 1, p = 0.22). The 2-year survivals (mean follow-up 2.1 years)
      were 83% and 84% in young and old patients, respectively (p = 0.72). In both
      groups, physical and mental QOL were lower than in the reference populations.
      CONCLUSIONS: We found that at 6 months after lung surgery old patients
      experienced deterioration in physical and mental health-related QOL similar to
      that of young patients. Survival also was similar in the two groups.

PMID- 20143072
TI  - The impact of intraoperative neuromonitoring (IONM) on surgical strategy in
      bilateral thyroid diseases: is it worth the effort?
AB  - BACKGROUND: Intraoperative nerve monitoring (IONM) of the recurrent laryngeal
      nerve and the vagal nerve can detect nonfunctioning nerves (recurrent laryngeal
      nerve palsy, RLNP) that are visibly intact. The use of IONM is questionable,
      however, as we still lack evidence that it reduces the rate of postoperative
      nerve injuries. Since negative IONM results after thyroid dissection of the first
      side could change our surgical strategy and thus could prevent patients from
      bilateral RLNP, we questioned whether IONM results are reliable enough to base
      changes in surgical strategy and whether this has any effect on surgical outcome.
      METHODS: We retrospectively analyzed the data of 1333 consecutive patients with
      suggested benign bilateral thyroid disease who had been operated on under a
      defined protocol, including the use of a specific IONM technique (tube electrodes
      and stimulation of the vagal nerve and the inferior recurrent nerve before and
      after thyroid resection), between January 1, 2006 and December 31, 2008. RESULTS:
      In four patients the IONM system did not work, two nerves had not been found, and
      in eight patients the tube had to be readjusted. Of five permanent nerve
      injuries, four were visible during surgery and one was suspected. Sensitivity of
      IONM in detecting temporary nerve injuries of macroscopically normal-appearing
      nerves was 93%. Specificity was 75-83% at first side of dissection and 55-67% at
      the second side, with an overall specificity of 77%. In 11 of 13 patients (85%)
      with known nerve injury (preexisting or visible) and in 20 of 36 patients (56%)
      with negative IONM stimulation at the first side of dissection, the surgical
      strategy was changed (specific surgeon or restricted resection) with no
      postoperative bilateral RLNP. This was in contrast to 3 of 18 (17%) bilateral
      RLNP (p < 0.05), when surgeons were not aware of a preexisting or highly likely
      nerve injury at the first side of thyroid dissection. CONCLUSIONS: Failed IONM
      stimulation of the vagal or recurrent laryngeal nerve after resection of the
      first thyroid lobe is specific enough to reconsider the surgical strategy in
      patients with bilateral thyroid disease to surely prevent bilateral RLNP.

PMID- 20143073
TI  - Intramuscular communicating branches in the flexor digitorum profundus:
      dissection and Sihler's staining.
AB  - PURPOSE: This study was designed to clarify the anatomy of the intramuscular
      communicating branch (ICb) between the median and ulnar nerves in the flexor
      digitorum profundus (FDP), and morphologically demonstrate the location of
      connection. METHODS: Twenty Korean cadavers were dissected and a further 8 were
      subjected to modified Sihler's staining to investigate the pattern of innervation
      of the ICb and the location of its communicating points in muscle. RESULTS: The
      median and ulnar nerves divided into small branches before entering FDP muscle.
      Of these small branches, one or two met inside the muscle. This communicating
      pattern could be classified into three types: type I, communicating branches in
      both the proximal and distal regions; type II, at least one communicating branch
      in the proximal region; type III, at least one communicating branch in the distal
      region. Of 20 dissected specimens, no case of type I was observed, but 3 cases of
      type II and 15 cases of type III were found. No ICbs at all were found in two of
      the dissected specimens. In eight stained specimens, one was classified as type
      I, two as type II, and five as type III. The proximal communicating branches were
      located at 34.1% from the interepicondylar line, inside the third muscle bundle.
      The distal communicating branches were located at 66.0% from the interepicondylar
      line, between third and fourth muscle bundles. CONCLUSIONS: These findings could
      provide critical anatomical information regarding the nerve distribution of FDP
      focused on the ICbs.

PMID- 20143074
TI  - Hydrocephalus shunt practice of experienced pediatric neurosurgeons.
AB  - OBJECTIVE: The objective of this study is to evaluate the ways experienced
      pediatric neurosurgeons insert ventriculo-peritoneal shunts and manage the
      shunted children afterward. METHODS: Seven pediatric neurosurgeons with extensive
      experience in hydrocephalus were surveyed about their choice of shunts, methods
      of shunt insertion, shunt follow-ups, management of incidental ventriculomegaly,
      and prevention of slit-ventricle syndrome. The author completed the survey also.
      RESULTS: No particular shunt was used by a majority of respondents, although
      differential pressure valves were used most often. Adjuncts to insert the
      ventricular catheter were used by half. Shunt catheters were inserted frontally
      in half and posteriorly in half. No one obtained annual follow-up scans after 5
      years of age, and no one operated on asymptomatic children with ventriculomegaly
      except perhaps in spina bifida cases. No techniques were identified to prevent
      slit-ventricle syndrome, but respondents emphasized the need for reticence in
      initial shunt insertions and in shunt revisions. CONCLUSIONS: There are
      substantial variations among extremely experienced pediatric neurosurgeons in
      their choice of shunts and their techniques of shunt insertion but reasonable
      uniformity in their frequency of follow-up, in not-obtaining routine scans after
      age five, and in rarely revising asymptomatic children. Methods to accurately
      position ventricular catheters and to prevent slit-ventricle syndrome need to be
      evaluated in multicenter studies.

PMID- 20143075
TI  - Intraoperative neurophysiology for surgery in and around the brainstem: role of
      brainstem mapping and corticobulbar tract motor-evoked potential monitoring.
AB  - INTRODUCTION: New advancements of intraoperative neurophysiology for surgery in
      and around the brainstem have been described. NEUROPHYSIOLOGICAL TECHNIQUES:
      Brainstem mapping (BSM) is applied to locate cranial nerves and their motor
      nuclei (CMN) on the floor of the fourth ventricle. Corticobulbar tract (CBT)
      motor-evoked potential (MEP) monitoring is used to achieve on-line monitoring of
      the cranial motor nerves' functional integrity. DISCUSSION: Each of these
      procedures bears a specific role: BSM can help avoid direct damage to CMNs on the
      fourth ventricular floor; CBT-MEP can provide simultaneous feedback on the
      functional integrity of the CBT and CMN during surgery, eventually leading to
      "tailored" modifications of the surgical procedure, based upon neurophysiological
      responses. CONCLUSIONS: CBT-MEP monitoring has less restriction in terms of
      clinical indications, but a combination of both procedures is essential for
      functional preservation of CMNs during surgery in and around the brainstem.

PMID- 20143076
TI  - Is neck flexion during a cerebrospinal fluid puncture a potentially hazardous
      maneuver?
AB  - INTRODUCTION: Cerebrospinal fluid puncture (CSFP) is a diagnostically meaningful
      procedure. We describe an acute tetraplegia in a patient as complication after
      CSFP. CASE HISTORIES: Cervical myelopathy due to posterior os odontoideum
      subluxation was diagnosed, and an occipitocervical fusion was performed
      surgically. No significant improvement of the neurological status was observed
      within the following 3 years. CONCLUSIONS: Neck flexion as performed during CSFP
      is a potentially hazardous maneuver. When patients show inconstant symptoms of
      craniocervical pathology or signs of cervical myelopathy, an os odontoideum
      should be suspected.

PMID- 20143077
TI  - A comparative study examining open inguinal herniotomy with and without
      hernioscopy to laparoscopic inguinal hernia repair in a pediatric population.
AB  - AIMS: Open herniotomy with or without hernioscopy has been performed in our unit
      for a decade. Since 2005 the laparoscopic repair was also introduced. The aims of
      this study were: (1) to compare detection rates for direct visualization of the
      contralateral deep inguinal ring via the known sac using a 70 degrees scope and
      via umbilical 30 degrees laparoscopy and (2) to compare operative timings,
      metachronous and recurrence rates for the three different management pathways for
      inguinal hernia. METHODS: A retrospective case note review was carried out over a
      29 month period since the introduction of the laparoscopic hernia repair. All
      patients with inguinal hernia were identified from the work load of six surgeons
      encompassing the three methods of hernia management. Case notes were retrieved
      and the data analyzed using SPSS v.17. RESULTS: A total of 308 patients had 326
      hernias performed. Follow-up ranged from 3 months to 1 year (median 8 months).
      The male-female ratio was 4:1. Of the patients, 12% were neonates; 299 children
      presented with unilateral hernia. Of those, 164 (55%) children had open
      herniotomy without contralateral inspection, and 5 (3%) had metachronous hernia;
      77 (26%) children had an open herniotomy with 70 degrees hernioscopy; 2 (3%)
      children, who were considered to have closed contralateral deep inguinal ring
      during hernioscopy, had metachronous hernia, and 58 (19%) children had a
      laparoscopic hernia repair and none of them had metachronous hernia. Detection of
      contralateral patent deep inguinal ring for 70 degrees hernioscopy and 30 degrees
      laparoscopy was 10 (13%) and 16 (28%), respectively (P = 0.0465). Operative
      timing was significantly longer for laparoscopic repair (P < or = 0.0001). During
      the study period there were 11 recurrences; 9 (5%) in the open only group and 2
      (3%) in the laparoscopic group. CONCLUSIONS: The results of the laparoscopic
      inguinal hernia repair are important for discussion as operative methods differ
      from that of herniotomy. The detection rate of contralateral patent deep inguinal
      ring appears to be higher for direct visualization via umbilical 30 degrees
      laparoscopy versus 70 degrees scope via the hernia sac. Whilst laparoscopy offers
      potential advantage of improved visualization, longer term prospective data
      collection is needed to compare these methods of operative hernia management.

PMID- 20143078
TI  - Autogenous non-vascularized fibula for treatment of giant cell tumor of distal
      end radius.
AB  - INTRODUCTION: Giant cell tumor of distal end of radius is treated by wide
      resection and intralesional procedures with former having better results. The
      various modalities for the defect created are vascularized/non-vascularized bone
      graft, osteoarticular allografts and custom-made prosthesis. We report outcome of
      wide resection and non-vascularized fibular grafting in biopsy-proven giant cell
      tumors. PATIENTS AND METHODS: Nine patients with mean age of 40 years with
      Campanacci grade II giant cell tumor of distal radius were managed with radical
      excision of the tumor and reconstruction with ipsilateral free fibular graft.
      RESULTS: Mean follow-up time was 56 months. One patient developed recurrence and
      was treated by amputation. All other patients showed a good union at fibular
      graft-radius junction. In wrist, average range of motion achieved at last follow
      up was 40 degrees  of dorsiflexion, 30 degrees  of palmar flexion, 45 degrees 
      each of supination and pronation. Major complications encountered included graft
      fracture (2), wrist subluxation (2), tourniquet palsy (1), aseptic graft
      resorption (1) and tumor recurrence (1). CONCLUSION: Reconstruction after wide
      excision by non-vascularized fibular graft is a viable alternative for giant cell
      tumors of the lower end of radius though it is a challenging procedure and may be
      accompanied by major complications.

PMID- 20143080
TI  - Polycystic ovaries: review of medical information on the internet for patients.
AB  - BACKGROUND: Often, internet can bring a sense of anxiety rather than information
      and understanding to the patient. Our aim was to assess the quality of
      information available for patients on the management of polycystic ovarian
      syndrome (PCOS) on the internet. MATERIALS AND METHODS: Five search engines were
      searched using phrases 'PCOS and 'patient information'. Various parameters of
      quality that were assessed were source, currency and editorial review process
      (for credibility) and hierarchy and accuracy of evidence (for content of the
      websites). RESULTS: Fifteen relevant websites were located, none of which
      complied with all the criteria for quality. Complete information on PCOS was not
      provided by any of the website to women according to the quality criteria.
      CONCLUSIONS: With 1,000 of websites launched everyday, it is difficult for
      patients to determine which website is trustworthy and valid. Patients need to be
      watchful about quality of the information on medical conditions in the internet.

PMID- 20143079
TI  - Two-stage total infected knee arthroplasty treatment with articulating cement
      spacer.
AB  - INTRODUCTION: The treatment of infected total knee arthroplasty (TKA) is
      controversial and various. Two-stage prolonged reimplantation and 6-week systemic
      antibiotics use have been a gold standard of treatment in recent years. PATIENTS:
      Seventeen knees of 17 patients, who underwent primary TKA and subsequently
      developed infections, were implanted articulating antibiotic-loaded cement spacer
      through two-stage reimplantation. In the postoperative period, parenteral
      antibiotic treatment targeting the specific microorganism detected in each
      patient was started and continued with oral administration. The mean total
      (parenteral and oral) antibiotic treatment time was 6.8 weeks (6-10). The spacer
      remained in its location until complete soft tissue recovery and normal values
      for laboratory parameters were achieved. The mean time interval between spacer
      implantation and reimplantation was 4.2 months (3-6). RESULTS: In the last follow
      up examinations of the patients, conditions requiring reoperation were detected
      in 3 patients (17.6%). In 2 of these patients (11.7%), infection developed after
      a mean 1-year interval. The joint motion ranges of the patients were measured in
      the preoperative period, during spacer use, and following reimplantation. The
      mean joint motion range of the patients was 58 degrees (12-90) in the
      preoperative period; in the presence of spacer between the two stages, 69 degrees
      (15-100); and in the last follow-up examination after reimplantation, 95 degrees
      (10-120). CONCLUSION: Use of articulating cement spacer in the treatment of
      infected TKA is efficient and reliable.

PMID- 20143081
TI  - Potentials and limits of pairwise kinship analysis using autosomal short tandem
      repeat loci.
AB  - At least in principle, most instances of complex kinship testing can be reduced
      to pairwise kinship cases involving two critical family members that either link
      or separate presumed sub-branches of a family. In the European population, the 34
      short tandem repeats (STRs) currently used in forensic genetics are sufficiently
      powerful to allow assessment of disputed first and second but not lower degrees
      of pairwise blood relatedness. We provide estimates of the means and variances of
      marker-specific log-likelihood ratios, using large-sample approximation and
      assuming different scenarios of pairwise kinship analysis. These estimates allow
      power calculations to be performed for any combination of the available STRs.
      Since some of the markers considered are physically linked, chromosome-wide
      likelihood calculations in kinship cases other than parent-child duos (and trios)
      have to take the reduced rates of meiotic inter-marker recombination into
      account. We show by simulation that this requirement may be ignored when
      discriminating distant hypotheses about kinship, but that linkage may play an
      important role in the biostatistical analysis of more intricate cases.

PMID- 20143082
TI  - Effects of nocturnal aircraft noise on cognitive performance in the following
      morning: dose-response relationships in laboratory and field.
AB  - OBJECTIVE: Nocturnal aircraft noise disturbs sleep and impairs recuperation. We
      investigated in laboratory and field studies whether noise-induced sleep
      fragmentation is associated with performance impairments in a psychomotor
      vigilance task (PVT) and a memory search task. METHODS: In the laboratory, 112
      participants were exposed to aircraft noise during 9 consecutive nights. In the
      field, 64 participants were examined during 9 consecutive nights in the vicinity
      of Cologne/Bonn airport. Reaction time, signal detection performance and
      subjective task load were recorded. RESULTS: Dose-response relationships showed
      significant, linear impairments in reaction times. In the laboratory, reaction
      time in PVT increased with 0.13 ms/dB equivalent noise level (LAeq) plus 0.02
      ms/noise event. In the field study, reaction time increased with 0.3 ms/dB LAeq.
      Participants worked significantly less accurate after nocturnal noise exposure.
      CONCLUSION: Influences of LAeq and number of noise events on daytime performance
      were small but consistent and significant, stressing the potential public health
      impact of nocturnal noise exposure.

PMID- 20143083
TI  - The influence of individual and contextual psychosocial work factors on the
      perception of the indoor environment at work: a multilevel analysis.
AB  - PURPOSE: The aim of this study was to investigate the role of the psychosocial
      work environment--at the individual level as well as the workplace level--in
      explaining the variability in the employees' perception of the indoor
      environment. METHODS: The perception of the indoor environment was surveyed by
      questionnaires among 3,281 employees in 39 randomly selected workplaces.
      Multilevel logistic regression analyses included individual-level and workplace
      level covariates to examine the effect of context. Associations between
      psychosocial risk factors at the workplace level and the employees' perception of
      the indoor environment was calculated as the interval odds ratios while between
      workplace variations were quantified by intraclass correlations and median odds
      ratios. RESULTS: We found moderate differences between the workplaces in the
      perception of the indoor environment, but large differences between individuals
      in the same building indicating that some occupants of a building do perceive
      problems in the indoor environment even in the absence of a general indoor air
      problem in the workplace. The type of organisation accounted for some of the
      variation in perceived indoor environment. Psychosocial work environment factors
      at the individual level, but not at the workplace-level, were associated with the
      individual perception of the indoor environment. In addition, an increased
      tendency to report symptoms was strongly associated with complaints about the
      indoor environment suggesting bias due to a tendency to "over-report".
      CONCLUSION: In studies investigating "sick buildings" contextual factors may be
      important. Multilevel analyses should be used in future research within
      workplaces where clustering could be expected.

PMID- 20143084
TI  - The effect of an adventure race on lymphocyte and neutrophil death.
AB  - The effect of an adventure race (Ecomotion Pro), which lasted for 4-5 days, on
      neutrophil and lymphocyte death from elite athletes was investigated. Blood was
      collected from 11 athletes at rest and after the adventure race. The following
      parameters of cell death were measured in neutrophils and lymphocytes: cell
      membrane integrity, DNA fragmentation, mitochondrial transmembrane depolarization
      and reactive oxygen species (ROS) production. Phagocytosis capacity was also
      evaluated in neutrophils. The adventure race raised the proportion of cells with
      the loss of membrane integrity; lymphocytes by 14% and neutrophils by 16.4%. The
      proportion of lymphocytes with DNA fragmentation (2.9-fold) and mitochondrial
      transmembrane depolarization (1.5-fold) increased. However, these parameters did
      not change in neutrophils. ROS production remained unchanged in lymphocytes,
      whereas an increase by 2.2-fold was found in neutrophils due to the race. Despite
      these changes, the phagocytosis capacity did not change in neutrophils after the
      race. In conclusion, the Ecomotion Pro race-induced neutrophil death by necrosis
      (as indicated by the loss of membrane integrity) and led to lymphocyte death by
      apoptosis (as indicated by increase DNA fragmentation and depolarization of
      mitochondrial membrane).

PMID- 20143085
TI  - Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum
      in children with coeliac disease.
AB  - Duodenal biopsy is an important tool to diagnose coeliac disease (CD); however,
      the most reliable location of biopsy site is still questionable. Claudins
      (CLDNs), members of a large family of adherent junction proteins, show
      characteristic expression pattern in inflammatory disorders; nevertheless, CLDN
      expression in CD is unknown. This is a comparative study to examine the CLDN 2, 3
      and 4 expressions in proximal and distal part of duodenum in children with CD and
      in controls. Thirty-three children with newly diagnosed CD were enrolled.
      Fourteen healthy children served as controls. Biopsies from proximal and distal
      part of duodenum were taken for routine histological analysis.
      Immunohistochemistry were used to detect CD3+ intraepithelial lymphocytes and
      CLDN 2, 3 and 4 protein expressions. Macroscopic picture, routine histology and
      Marsh grade depicted no differences between biopsies taken from proximal or
      distal part of duodenum. However, CLDN 2 expression was significantly increased
      in severe form of coeliac disease in bulb and in distal duodenum, and in distal
      part of non-severe coeliac patients, in comparison to controls. Similar
      association was found concerning CLDN 3 expression. Expression of CLDN 4 was
      similar in all groups studied. Both proximal and distal mucosal duodenal biopsies
      are suitable for diagnosing villous atrophy in patients with CD. Increased
      expressions of CLDN 2 and 3 suggest structural changes of tight junction in
      coeliac disease which may be, at least in part, responsible for increased
      permeability and proliferation observed in coeliac disease.

PMID- 20143086
TI  - Microvessel density and the association with single nucleotide polymorphisms of
      the vascular endothelial growth factor receptor 2 in patients with colorectal
      cancer.
AB  - The measurement of microvessel density (MVD) is a widely accepted method for
      assessing the neoangiogenetic activity in neoplasia. The aim of the present study
      was to compare MVD with single nucleotide polymorphisms (SNPs) in the vascular
      endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 genes and, furthermore,
      with quantitative measurements of the receptors in colorectal cancer (CRC)
      tissue. Prognosis was also assessed. Blood and tissue were collected from 110
      patients surgically resected for CRC. SNPs were analysed from genomic DNA by
      polymerase chain reaction. MVD was assessed by immunohistochemistry using CD34
      and CD105 combined with caldesmon in order to identify also immature vessels.
      Microvessels were counted in three fields of vision, and the mean MVD was used
      for statistical analysis. The VEGFR-2 1192 C/T and -604 T/C SNPs were associated
      with the MVD assessed by CD105. The median MVD score for the 1192 CC genotype was
      significantly lower compared to the CT + TT genotypes (p = 0.002). The median MVD
      score for the -604 CC genotype was significantly higher compared to the TT + TC
      genotypes (p = 0.009). A possible association, although non-significant, was
      demonstrated for the CD34-positive microvessels. The 1192 CC genotype and the 
      604 TT + TC genotypes correlated with improved survival. This is the first report
      on correlations between SNPs in the VEGF receptor genes and MVD in patients with
      CRC. Associations were shown between two SNPs in the VEGFR-2 gene and the CD105
      positive microvessels indicating an impact on neoangiogenesis. Moreover, an
      association between the SNPs and survival was demonstrated. The clinical
      implications of these findings need further investigations.

PMID- 20143087
TI  - Mucosal innate response stimulation induced by lipopolysaccharide protects
      against Bordetella pertussis colonization.
AB  - Non-specific enhancement of the airways innate response has been shown to impair
      lung infections in several models of infection such diverse as influenza A,
      Streptococcus pneumoniae, and Aspergillus niger. Our aim was to evaluate whether
      a similar event could operate in the context of Bordetella pertussis respiratory
      infection, not only to enrich the knowledge of host-bacteria interaction but also
      to establish immunological basis for the development of new control strategies
      against the pathogen. Using a B. pertussis intranasal infection model and
      coadministration of different TLR agonists at the moment of the infection, we
      observed that the enhancement of innate response activation, in a TLR4-dependent
      way, could efficiently impair B. pertussis colonization (P < 0.001). While LPS
      from different microbial sources were equally effective in promoting this effect,
      flagellin and poly I:C coadministration, in spite of inducing expression of
      innate response markers TNFalpha, CXCL2, CXCL10 and IL6, was not effective to
      prevent B. pertussis colonization. Our results indicate that during the early
      stage of infection, specific anti-microbial mechanisms triggered by TLR4
      stimulation are able to impair B. pertussis colonization. These findings could
      complement our current view of the role of TLR4-dependent processes that
      contribute to anti-pertussis immunity.

PMID- 20143088
TI  - Catecholaminergic polymorphic ventricular tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited
      arrhythmogenic disorder that causes syncopal episodes related with stress or
      emotion and even sudden cardiac deaths. Signs and symptoms usually begin in
      childhood. A suspicion of CPVT should be kept in mind when a child or an
      adolescent suddenly loses consciousness, particularly if this happens upon
      physical exercise or sudden mental stress. During the past decade, the knowledge
      of CPVT genetics and physiology has increased. Exercise testing is essential when
      suspecting arrhythmogenic origin of syncope, and in the case of CPVT, it may be
      even more sensitive than Holter monitoring. Beta-antiadrenergic medication can
      substantially decrease the mortality associated with CPVT. Asymptomatic patients
      with known CPVT gene defects should also be treated because sudden cardiac death
      may be the first manifestation of the disease. An implantable cardioverter
      defibrillator may also be required in the most severe CPVT cases. In this review,
      we summarise the current knowledge on the clinical characteristics, diagnostic,
      genetic and prognostic features of CPVT in children. In all, 133 publications
      covering 60 years were checked, and those written in English and containing ten
      or more, mainly paediatric CPVT cases, were included. In addition, a CPVT family
      with three members and delayed diagnoses until late childhood and adulthood is
      presented.

PMID- 20143089
TI  - Smoking and smoking cessation during pregnancy.

PMID- 20143090
TI  - Molecular identification of Probolocoryphe uca (Sarkisian, 1957; Digenea:
      Microphallidae) from Kuwait Bay using ITS1 and ITS2 sequences.
AB  - Probolocoryphe species occur primarily as intestinal parasites of birds and
      mammals. Infection of the crab Nanosesarma minutum with the metacercarial cyst
      stages of Probolocoryphe uca is common in Kuwait Bay. In this study, the snail
      Cerithidea cingulata was used to determine if it would serve as first
      intermediate host in the parasite's life cycle. To determine the snail-crab link
      in the life cycle of P. uca based on rDNA molecular data, ribosomal internal
      transcribed spacer (ITS) regions of the metacercarial cyst stage from the crab N.
      minutum and the sporocyst stage from the snail C. cingulata were sequenced and
      compared. Sequence alignment clearly demonstrated that the sporocysts and
      metacercariae belonged to P. uca. Comparisons were also made between the ITS
      sequences of P. uca and other digenean species available in GenBank. NCBI
      databases were used for sequence homology analysis using BLAST, ClustalW, and
      MUSCLE. The phylogenetic trees based on the homology analysis of the ITS (1 and
      2) sequences constructed using PHYLIP and MEGA 4.0 confirmed the identification
      and positioned P. uca in the Microphallidae family.

PMID- 20143091
TI  - Light and transmission electron microscopic studies on the encystation of
      Histomonas meleagridis.
AB  - The study deals with the pleomorphic zooflagellate Histomonas meleagridis, which
      was cultivated under different stress conditions to induce a possible
      encystation. In the present paper, the morphological changes were analyzed by
      light and electron microscopy. The determination of the proliferation under
      different adverse conditions led to conclusions on the tenacity of the
      flagellate. H. meleagridis parasitizes in the intestinal tract of galliform birds
      and may cause enormous losses in poultry farming. For the development of new
      therapy approaches, clarification of the transmission pathways will be helpful.
      Different clonal cultures of H. meleagridis established by micromanipulation and
      exposed to media lacking different ingredients, inappropriate temperatures,
      and/or distinct reagents were investigated. Lowering of temperature was proven to
      have adverse effects on the survival of H. meleagridis. The flagellate could not
      survive in a frozen medium, and survival in a temperature of 4 degrees C lasted
      no longer than 23 h. An addition of sodium chloride induced an increased
      proliferation; pH values between 2 and 8 set limits for the survival of the
      parasite in different ways. H. meleagridis was able to survive under high acidic
      conditions for only 1 h. The major amount of cells, which could be discovered in
      the controls, measured 8-12 microm appeared amoebic (stage 1) and were filled
      with enclosures of rice starch. A rounding of most cells was noted 4 h at 4
      degrees C after incubation in minimal essential medium in the absence of rice
      starch and fetal calf serum. A higher osmolarity of the medium, which was
      initiated by the addition of sodium chloride or magnesium chloride, did not
      induce an encystation process. After addition of hypochlorite base and
      cultivating at pH values between 7 and 8, spherical stages without a flagellum
      were formed (stage 2) measuring about 8-12 microm in diameter. Their interior
      consisted of a central and a peripheral region when studied by transmission
      electron microscopy. This aspect was due to the location of the glycogen
      granules. The central zone was described as totally filled with the
      carbohydrates, which made totally invisible the other organelles. The solidity of
      the amorphous layer below the cell membrane seemed to hinder the invasion of the
      glycogen granules. The amorphous layer below the cell membrane made it apparently
      possible that the cell might survive under adverse conditions-at least for a
      short time. This special structure might enable H. meleagridis to proceed a fast
      transmission and to infect many birds in a rather short time, which was shown in
      the past by several studies. Double-membraned cells, which were guessed to be
      cyst-like structures of the parasite, were also detected (stage 3). The size of
      these cells, however, was much smaller than that of the amoebic stages or the
      above-described spherical forms of H. meleagridis. Furthermore, the small cells
      were characterized by other granula structures. These findings might be
      interpreted that the small stages are possibly long-term (true) cysts and that
      the spherical stages with the amorphous layer beneath the cell membrane might be
      short-term cysts. Both, however, should be able to survive situations outside of
      a body and thus might be transmitted from feces to another animal.

PMID- 20143092
TI  - The Nf-actin gene is an important factor for food-cup formation and cytotoxicity
      of pathogenic Naegleria fowleri.
AB  - Naegleria fowleri destroys target cells by trogocytosis, a phagocytosis
      mechanism, and a process of piecemeal ingestion of target cells by food-cups.
      Phagocytosis is an actin-dependent process that involves polymerization of
      monomeric G-actin into filamentous F-actin. However, despite the numerous studies
      concerning phagocytosis, its role in the N. fowleri food-cup formation related
      with trogocytosis has been poorly reported. In this study, we cloned and
      characterized an Nf-actin gene to elucidate the role of Nf-actin gene in N.
      fowleri pathogenesis. The Nf-actin gene is composed of 1,128-bp and produced a
      54.1-kDa recombinant protein (Nf-actin). The sequence identity was 82% with
      nonpathogenic Naegleria gruberi but has no sequence identity with other mammals
      or human actin gene. Anti-Nf-actin polyclonal antibody was produced in BALB/c
      mice immunized with recombinant Nf-actin. The Nf-actin was localized on the
      cytoplasm, pseudopodia, and especially, food-cup structure (amoebastome) in N.
      fowleri trophozoites using immunofluorescence assay. When N. fowleri co-cultured
      with Chinese hamster ovary cells, Nf-actin was observed to localize around on
      phagocytic food-cups. We also observed that N. fowleri treated with cytochalasin
      D as actin polymerization inhibitor or transfected with antisense oligomer of Nf
      actin gene had shown the reduced ability of food-cup formation and in vitro
      cytotoxicity. Finally, it suggests that Nf-actin plays an important role in
      phagocytic activity of pathogenic N. fowleri.

PMID- 20143093
TI  - A cross-sectional study of trypanosomosis and its vectors in donkeys and mules in
      Northwest Ethiopia.
AB  - A preliminary study was conducted in January 2009 in four peasant associations
      (PAs) selected from two districts in Benishangul Gumuz Regional State, Northwest
      Ethiopia to investigate the prevalence and species of trypanosomes infecting
      donkeys and mules and identify the fly vectors playing a role in the transmission
      of trypanosomosis. Blood samples were collected from a total of 334 donkeys and
      52 mules and examined by dark ground/phase contrast buffy coat technique and
      Giemsa-stained blood smears. Accordingly, trypanosome species were encountered in
      6.3% of the examined donkeys (n = 21) while none of the mules examined was
      positive for trypanosome infection. Trypanosomes and tsetse flies were detected
      in two of the four PAs surveyed (Tsetsa adurno and Bamadone) with significant (P
      = 0.004) difference in prevalence. The inability to find trypanosomes in the
      other two PAs (Ura and Ashura) was most likely due to the absence of appropriate
      fly vectors. Three species of trypanosomes were detected in donkeys, which in
      order of predominance were Trypanosoma congolense (52.4%), Trypanosoma brucei
      (28.6%), and Trypanosoma vivax (19.05%). There was a significant (P = 0.008)
      difference in mean PCV between trypanosome infected and non-infected donkeys. The
      body condition score of the donkeys was significantly associated with both
      prevalence of infection (P = 0.009) and mean packed cell volume (PCV; P <
      0.0001). No significant difference was observed between male and female donkeys
      regarding both prevalence of infection and mean PCV (P > 0.05 for each factor).
      The entomological surveys revealed the presence of Glossina morsitans
      submorsitans and other biting flies of the family Stomoxys, Tabanus, and
      Haematopota. In conclusion, the prevalence of trypanosomosis obtained in the
      current study is generally low compared to previous studies. As the present study
      design was a cross-sectional, one that only depicts a momentary picture of the
      infection status in the herd, a further longitudinal study that makes use of more
      sensitive techniques and entomological survey is recommended.

PMID- 20143094
TI  - Mitochondrial membrane potential-based genome-wide RNAi screen of Trypanosoma
      brucei.
AB  - We have screened the Trypanosoma brucei genome-wide RNAi library by staining the
      procyclics with the dye JC-1 followed by sorting the differentially stained cells
      by flow cytometry. This allowed us to highly enrich for cells in which
      mitochondrial membrane potential was decreased. We have further validated a
      subset of selected clones by a reverse approach in which we showed that cloning
      the selected genomic regions into another RNAi vector also results in a drop in
      mitochondrial membrane potential.

PMID- 20143095
TI  - Application of recombinant Echinococcus granulosus antigen B to ELISA kits for
      diagnosing hydatidosis.
AB  - Echinococcus granulosus causes human cystic echinococcosis as an important public
      health problem in many regions of the world. There are some problems in primary
      diagnosis such as cross-reaction with sera from patients with other parasitic
      disease in serological tests. The use of an appropriate source of antigenic
      material is a very important and crucial point in the improvement of the
      serodiagnostic features such as enzyme-linked immunosorbent assay (ELISA) method.
      We expressed and purified recombinant AgB of Echinococcus granulosus and used as
      antigen in ELISA method. Serum samples were given from 36 cystic hydatid disease
      patients that have been confirmed by surgical operation as well as 36 healthy
      individuals sera were tested by ELISA method using recombinant AgB and compared
      with commercial kit (Euroimmun) for specificity and sensitivities value. The
      sensitivity of 91.66% and specificity of 97.22% were determined by homemade kit.

PMID- 20143096
TI  - A survey of airway responsiveness in 36 inbred mouse strains facilitates gene
      mapping studies and identification of quantitative trait loci.
AB  - Airway hyper-responsiveness (AHR) is a critical phenotype of human asthma and
      animal models of asthma. Other studies have measured AHR in nine mouse strains,
      but only six strains have been used to identify genetic loci underlying AHR. Our
      goals were to increase the genetic diversity of available strains by surveying 27
      additional strains, to apply haplotype association mapping to the 36-strain
      survey, and to identify new genetic determinants for AHR. We derived AHR from the
      increase in airway resistance in females subjected to increasing levels of
      methacholine concentrations. We used haplotype association mapping to identify
      associations between AHR and haplotypes on chromosomes 3, 5, 8, 12, 13, and 14.
      And we used bioinformatics techniques to narrow the identified region on
      chromosome 13, reducing the region to 29 candidate genes, with 11 of considerable
      interest. Our combined use of haplotype association mapping with bioinformatics
      tools is the first study of its kind for AHR on these 36 strains of mice. Our
      analyses have narrowed the possible QTL genes and will facilitate the discovery
      of novel genes that regulate AHR in mice.

PMID- 20143097
TI  - Evaluation of peritoneal capacity for peritoneal dialysis after abdominal
      surgery.

PMID- 20143099
TI  - Hypertension and hypokalemia in a 15-year-old boy: question.

PMID- 20143100
TI  - [Elevated postoperative pain levels following orthopedic surgery. Depression as a
      strong predictor].
AB  - The aim of this study was to examine whether depression is a strong predictor of
      elevated postoperative pain levels following orthopedic surgery and whether the
      implementation of standardized pain management is more beneficial for patients
      with depression. We performed a non-randomized, prospective study with two
      different groups of patients who underwent orthopedic surgery. Group 1 (n=249)
      received non-standardized pain therapy whereas group 2 (n = 243) was treated with
      a standardized pain management concept. Effects of the treatment were monitored
      with a VAS-based pain assessment protocol. Depression was measured preoperatively
      with the self-reported Patient Health Questionnaire (PHQ-9). Patients with the
      probable diagnosis of a current episode of major depression showed significantly
      higher postoperative pain than patients without a depressive episode. On the
      other hand, patients with depression benefited from the implementation of
      standardized pain management. Our data suggest a predictive value of depression
      for severe postoperative pain. Patients with depression benefited from
      standardized postoperative pain therapy, but were still suffering from
      significantly higher postoperative pain.

PMID- 20143101
TI  - [Quality of life and alexithymia in somatoform pain disorder].
AB  - BACKGROUND: Patients with somatoform pain disorders (SPD) frequently display
      reduced quality of life (QoL) and increased levels of alexithymia. This study
      investigated the association of QoL and alexithymia in a sample of SPD. PATIENTS
      AND METHODS: Fifty-one patients with SPD (average time since onset: 11.6 years)
      were assessed in terms of alexithymia (TAS-20), QoL (WHOQOL-BREF), psychological
      distress and somatisation (SCL-90-R), and depression (MADRS). RESULTS: In SPD
      patients a significant negative correlation was observed between QoL and
      alexithymia, particularly the psychological domain of QoL and the TAS-20 total
      score (r=-.63, p<.001). The TAS-20 subscale "Difficulty Describing Feelings" was
      revealed to be a significant predictor of the psychological domain of QoL (beta=
      .34, p<.01), even after controlling for depression, somatisation and gender.
      CONCLUSION: Patients with SPD show a remarkably reduced QoL and alexithymia
      appears to play a significant role for low QoL. Clinicians need to pay careful
      attention to alexithymia with regard to diagnosis and treatment planning in SPD
      patients.

PMID- 20143102
TI  - Phase 2 pilot study of Pathfinders: a psychosocial intervention for cancer
      patients.
AB  - PURPOSE: Pathfinders is a multi-faceted psychosocial care program for cancer
      patients; it was developed in community oncology and adapted to the academic
      oncology setting. This prospective, single-arm, phase 2 pilot study examined the
      acceptability and feasibility of Pathfinders for women with metastatic breast
      cancer. METHODS: Over 3 months, participants completed patient-reported surveys
      including the Patient Care Monitor (PCM, review of systems), Functional
      Assessment of Chronic Illness Therapy-Breast Cancer (FACT-B), Self Efficacy, and
      a single-item survey asking patients whether the program was helpful to them. A
      technology-based data collection system was used to capture electronic patient
      reported outcomes at point of care, report symptoms in real time to clinicians,
      and collect warehouse data to provide a detailed longitudinal picture of the
      patient experience when receiving Pathfinders. RESULTS: Participants (n = 50)
      were: mean age 51 (SD 11); 76% white, 20% black; 74% married; 50% college degree.
      Forty-two (n = 42) patients completed baseline and 3-month assessments.
      Statistically significant improvements (all P < 0.05) occurred in PCM subscales
      for Distress (mean [SE] = -3.42 [1.21]), Despair (-4.53 [1.56]), and Quality of
      Life (2.88 [0.97]), and the FACT-B Emotional Wellbeing subscale (2.07 [0.46]). Of
      the 29 participants asked if Pathfinders was helpful, 27 (93%) responded
      positively and two did not respond. Other instruments measuring symptoms, quality
      of life, and self-efficacy showed improvement. CONCLUSIONS: In a phase 2 pilot
      study, Pathfinders was helpful to patients and is feasible in an academic medical
      center. Follow-up data collected at the 3-month assessment suggest that the
      program impacts various psychological outcomes, notably distress and despair.

PMID- 20143103
TI  - Wireless capsule endoscopy in pediatric patients: the first series from Japan.
AB  - PURPOSE: The aim of our study was to determine the safety and usefulness of
      capsule endoscopy (CE) in pediatric patients. METHODS: We prospectively examined
      children (aged 10-18 years) with suspected small bowel disease and recorded
      capsule transit times, findings, and complications. RESULTS: We performed 19 CE
      examinations in 12 patients (median age 11.8 years; range 10-18 years). One of
      the two patients with obscure gastrointestinal bleeding (OGIB), a 14-year-old
      girl whose OGIB occurred after cord-blood transplantation due to leukemia, was
      diagnosed with thrombotic microangiopathy. Repeated CE allowed visualization of
      real-time mucosal changes, such as the improvement of ulcers and bleeding, and
      newly emerged lymphangiectasia, without causing the patient physical and mental
      stress. This information facilitated both subsequent evaluation of the clinical
      course and determination of the appropriate treatment strategy. In the second
      patient with chronic OGIB, a 10-year-old girl, the detection of severe ileal
      stenoses by capsule retention led to the diagnosis of non-specific multiple
      ulcers of the small intestine. After ileal resection, repeated CE detected the
      recurrence of multiple ulcers and enabled the optimal treatment strategy to be
      applied. CE confirmed small bowel involvement in a patient with unresponsive
      Crohn's disease (CD) and excluded CD in all five patients with suspected CD.
      Similarly, CE confirmed the absence of small bowel involvement in three of the
      four patients with recurrent abdominal pain, although one patient had nodular
      lymphoid hyperplasia. CONCLUSIONS: Based on our results, CE is a valuable tool in
      the differential diagnoses of small bowel diseases, and repeated examination can
      provide real-time information that will enable evaluation of the clinical course
      in pediatric patients.

PMID- 20143104
TI  - Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane
      pretreated rats with long-term feeding of diet containing beef tallow.
AB  - BACKGROUND: We have indicated previously that long-term feeding of beef tallow
      increases colorectal cancer in rats. In this study, we investigated the effects
      of conjugated linoleic acid (CLA) on colon carcinogenesis in rats under long-term
      feeding of beef tallow diets, pretreated with azoxymethane (AOM). METHODS: Six
      week-old male Sprague-Dawley rats were fed with 10% beef tallow diet only, 10%
      beef tallow with 1% CLA in triglyceride form (CLA-TG), or 10% beef tallow with 1%
      CLA in free fatty acid form (CLA-FFA). Colon carcinogenesis was induced by two
      intraperitoneal injections of AOM. Aberrant crypt foci (ACFs) were examined at 12
      weeks. Cancer, cell proliferation, apoptosis, Wnt signaling, and the arachidonic
      acid cascade were examined at 44 weeks. RESULTS: At 12 weeks, CLA-TG and CLA-FFA
      attenuated the increase in ACFs induced by 10% beef tallow and AOM pretreatment.
      At 44 weeks, both forms of CLA attenuated multiple colon cancers, and CLA-FFA
      reduced the incidence of colon cancer to 50% of that seen with CLA-TG. CLA-TG and
      CLA-FFA decreased the number of 5-bromo-2'-deoxyuridine-positive cells in AOM
      pretreated rats fed with 10% beef tallow. CLA-FFA increased the number of
      apoptotic cells and the activity of caspase-3 in the colon mucosa, and CLA-TG
      enhanced the activity of caspase-3. Both forms of CLA suppressed Wnt signaling
      and the arachidonic acid cascade in rats treated with beef tallow and AOM.
      CONCLUSION: These results suggested that CLA-TG and CLA-FFA suppressed colon
      carcinogenesis in rats with long-term feeding of a 10% beef tallow diet, through
      several mechanisms. The results of the present study with rats might be
      applicable to humans.

PMID- 20143105
TI  - The transdural approach for thoracic disc herniations: a technical note.
AB  - Surgery for thoracic disc herniations is still challenging, and the disc excision
      via a posterior laminectomy is considered risky. A variety of dorsolateral and
      ventral approaches have been developed. However, the lateral extracavitary and
      transthoracic approach require extensive surgical exposure. Therefore, we adopted
      a posterior transdural approach for direct visualization without entry into the
      thoracic cavity. Three cases that illustrate this procedure are reported here
      with the preoperative findings, radiological findings and surgical techniques
      used. After the laminectomy, at the involved level, the dorsal dura was opened
      with a longitudinal paramedian incision. The cerebrospinal fluid was drained to
      gain more operating space. After sectioning of the dentate ligaments, gentle
      retraction was applied to the spinal cord. Between the rootlets above and below,
      the ventral dural bulging was clearly observed. A small paramedian dural incision
      was made over the disc space and the protruded disc fragment was removed.
      Neurological symptoms were improved, and no surgery-related complication was
      encountered. The posterior transdural approach may offer an alternative surgical
      option for selected patients with thoracic paracentral soft discs, while limiting
      the morbidity associated with the exposure.

PMID- 20143106
TI  - Clinical and genetic features in a family with CADASIL and high lipoprotein (a)
      values.
AB  - We present a family with cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL) and elevated
      lipoprotein(a) [Lp(a)] levels. In addition to neurological examinations,
      ultrasound of extra- and intracranial arteries, laboratory tests, and cerebral
      magnetic resonance imaging (MRI), a whole genome screening with mutation analyses
      was performed. Rather untypical for CADASIL, stenoses of large intracranial
      arteries were detected in the index patient. All affected subjects lacked a
      history of migraine, mood disturbances, and cognitive decline despite extensive
      white matter lesions in two individuals. Furthermore, evidence of early cerebral
      microangiopathy was demonstrated in three children (age 9, 11 and 13). We were
      able to explain the mechanism of elevated Lp(a) on the basis of the kringle IV
      type 2 repetition size. A mutation S118C located in exon 4 of Notch3 was
      responsible for CADASIL. Elevated Lp(a) might have contributed to the
      cerebrovascular phenotype in this family.

PMID- 20143107
TI  - Lifetime prevalence and incidence of parasomnias in a population of young adult
      Nigerians.
AB  - Lifetime prevalence, incidence, and risk factors for parasomnias were determined.
      Past experiences of non-REM, REM, and sleep-transition parasomnias were recorded.
      Diaries of night sleep duration, parasomnias, perception of aliens, levels of
      physical activity, headaches and intake of all substances, drugs, and tobacco
      were kept for 14 consecutive days. A total of 276 subjects were studied. Lifetime
      prevalences (95% CI) were 725 (668-776) for occurrence of any parasomnia, 43 (25
      74) for sleepwalking, 112 (80-155) for sleep terror, 475 (416-533) for
      nightmares, 225 (179-277) for sleep paralysis, 43 (25-74) for sleep starts, 322
      (270-380) for sleep talking, and 344 (291-402) for enuresis. Incidences (95% CI)
      were 210 (166-262) for occurrence of any parasomnia, 14 (6-37) for sleepwalking,
      11 (4-31) for sleep terror, 170 (131-219) for confusional arousal, 18 (8-42) for
      nightmares, 14 (6-37) for sleep paralysis, 33 (17-61) for sleep starts, and 4 (1
      20) for sleep enuresis. Multivariate analysis showed associations of increase
      occurrence of parasomnias and duration of sleep >7 h (p < 0.05) and intake of
      alcohol (p < 0.001), but heavy workload before sleep was associated with
      decreased occurrence of parasomnias (p < 0.01). Gender, smoking, caffeinated
      drinks, hypnotics, and headaches were not associated with parasomnias. Incidence
      of presence of aliens (95% CI) in the room was 25(0/infinity) (12-51). This study
      shows that more than 70% of the population have experienced parasomnias at any
      time in the past. Nightmares, enuresis, sleep paralysis and night terrors are the
      commonest parasomnias experienced in the past, while confusional arousal, sleep
      starts, and nightmares are the commonest parasomnias currently experienced.
      Incidence estimates show that all parasomnias persist into adulthood at reduced
      rates, but reduction of occurrence was greatest for enuresis. Long duration of
      night sleep and intake of alcohol predisposed subjects to higher occurrence of
      parasomnias.

PMID- 20143108
TI  - Communication in conversation in stroke patients.
AB  - In stroke patients, it has been suggested that communication disorders could
      result from lexical and syntactic disorders in left hemisphere lesions and from
      pragmatics problems in right lesions. However, we have little information on
      patient behaviour in dyadic communication, especially in conversation. Here, we
      analyzed the various processes participating in communication difficulties at the
      rehabilitation phase (1-6 months) post-stroke, in order to define the main
      mechanisms of verbal and non-verbal communication (VC, NVC) disorders and their
      relationship with aphasic disorders. Sixty-three patients were recruited, who
      belonged to six groups, with left or right cortico-sub-cortical (L-CSC, R-CSC) or
      sub-cortical (L-SC, R-SC), frontal (Fro) or posterior fossa (PF) lesions. They
      were compared with an equivalent control group (gender, age, education level). We
      used the Lille Communication Test, which comprises three parts: participation to
      communication (greeting, attention, engagement), verbal communication (verbal
      comprehension, speech outflow, intelligibility, word production, syntax, verbal
      pragmatics and verbal feedback) and non-verbal communication (understanding
      gestures, affective expressivity, producing gestures, pragmatics and feedback).
      We also used the Functional Communication Profile and the Boston Diagnostic
      Aphasia Examination (BDAE). Decrease in participation was found in L-CSC, R-CSC
      and Fro patients. Verbal communication was essentially disrupted in L-SCS and L
      SC groups, including by verbal pragmatic disorders, and to a lesser degree in
      frontal patients. Nonverbal communication was mainly affected in R-CSC patients,
      especially by pragmatic difficulties. L-CSC patients showed an increase in
      gesture production, compensating for aphasia. In conclusion, communication
      disorders were relatively complex and could not be summarised by syntactical and
      lexical difficulties in left stroke and pragmatic problems in right stroke. The
      former also showed severe verbal pragmatic difficulties. Frontal stroke also
      resulted in evident verbal and non-verbal disorders.

PMID- 20143109
TI  - An fMRI study of musicians with focal dystonia during tapping tasks.
AB  - Musician's dystonia is a type of task specific dystonia for which the
      pathophysiology is not clear. In this study, we performed functional magnetic
      resonance imaging to investigate the motor-related brain activity associated with
      musician's dystonia. We compared brain activities measured from subjects with
      focal hand dystonia and normal (control) musicians during right-hand, left-hand,
      and both-hands tapping tasks. We found activations in the thalamus and the basal
      ganglia during the tapping tasks in the control group but not in the dystonia
      group. For both groups, we detected significant activations in the contralateral
      sensorimotor areas, including the premotor area and cerebellum, during each
      tapping task. Moreover, direct comparison between the dystonia and control groups
      showed that the dystonia group had greater activity in the ipsilateral premotor
      area during the right-hand tapping task and less activity in the left cerebellum
      during the both-hands tapping task. Thus, the dystonic musicians showed irregular
      activation patterns in the motor-association system. We suggest that irregular
      neural activity patterns in dystonic subjects reflect dystonic neural malfunction
      and consequent compensatory activity to maintain appropriate voluntary movements.

PMID- 20143111
TI  - Traction lesion of the brachial plexus during bodyflying.

PMID- 20143110
TI  - A preliminary longitudinal study of the retinal nerve fiber layer in progressive
      multiple sclerosis.
AB  - Thinning of the retinal nerve fiber layer (RNFL) of clinically unaffected eyes is
      seen in patients with multiple sclerosis (MS). It is uncertain when this thinning
      occurs, and whether ongoing RNFL loss can be measured over time with optical
      coherence tomography (OCT). Using time-domain OCT, we studied 34 patients with
      progressive MS (16 primary progressive MS, 18 secondary progressive; 14 male; 20
      female; mean age at study entry 51 years; median EDSS 6; mean disease duration at
      study entry 12 years) on two occasions with a median interval of 575 (range 411
      895) days apart. Eighteen healthy controls (10 male; eight female; mean age at
      study entry 46 years) were also studied twice, with a median interval of 656 days
      (range 398-890). Compared to controls, the patients had significant decreases in
      the RNFL thickness and macular volume of their clinically unaffected eyes at
      study entry. No significant decrease in RNFL thickness was observed between
      baseline and follow-up in either patients or controls. Macular volume declined
      significantly in patients and controls, but there was no difference in this
      change between the two groups. The study findings suggest that time domain OCT
      detects little disease-related ongoing loss of retinal axons in progressive forms
      of MS and has limited use for monitoring potential neuroprotective therapies at
      this stage of disease. Further studies are needed using higher-resolution OCT
      systems and in larger groups of patients, to elucidate the timing and mechanism
      of RNFL loss that is observed in clinically unaffected nerves in MS.

PMID- 20143112
TI  - Editorial: Structure and function of plants in extreme environments.

PMID- 20143113
TI  - Laccase-catalyzed cross-linking of amino acids and peptides with dihydroxylated
      aromatic compounds.
AB  - In order to design potential biomaterials, we investigated the laccase-catalyzed
      cross-linking between L-lysine or lysine-containing peptides and dihydroxylated
      aromatics. L-Lysine is one of the major components of naturally occurring mussel
      adhesive proteins (MAPs). Dihydroxylated aromatics are structurally related to
      3,4-dihydroxyphenyl-L-alanine, another main component of MAPs. Mass spectrometry
      and nuclear magnetic resonance analyses show that the epsilon-amino group of L
      lysine is able to cross-link dihydroxylated aromatics. Additional oligomer and
      polymer cross-linked products were obtained from di- and oligopeptides containing
      L-lysine. Potential applications in medicine or industry for biomaterials
      synthesised via the three component system consisting of the oligopeptide [Tyr
      Lys]10, dihydroxylated aromatics and laccase are discussed.

PMID- 20143114
TI  - Optimized synthesis of phosphatidylserine.
AB  - The synthesis of phosphatidyl serine containing saturated fatty acids was
      thoroughly studied and optimized in order to establish a protocol amenable to
      large-scale synthesis. The key step was a one-pot multicomponent reaction
      involving an O-benzyl phosphorodiamidite, protected serine and diacylglycerol,
      followed by in situ oxidation of the resulting phosphite. In order to replace
      expensive and poorly stable tetrazole, a screening of substitutes was carried out
      and imidazolium chloride was selected as the best suited one.

PMID- 20143115
TI  - A strategy to avoid facial mutilation in orbital embryonal rhabdomyosarcoma.
AB  - INTRODUCTION: An orbital embryonal rhabdomyosarcoma (RMS) is a rare malignancy in
      children, but clinical findings are typical. We detail the case of an 8-year-old
      female with orbital RMS and discuss the therapeutic options. CASE REPORT: Orbital
      RMS was apparent with painless exophthalmos of the right globe and diplopia. Head
      MRI showed tumor masses behind and inferior to the globe. Open biopsy led to the
      histological diagnosis. Metastasis or infiltration of orbital bone was not
      observed. Chemotherapy was carried out in accordance with the Cooperative
      Weichteilsarkom Studie (CWS) 2002 protocol. Tumor regression was detected after
      the first course of chemotherapy; we decided to excise the residual tumor with
      preservation of the globe. The CWS 2002 protocol was subsequently completed.
      Radiotherapy was not done. One year after treatment, RMS recurrence was not
      observed. CONCLUSION: After interdisciplinary treatment, mutilation was avoided
      after exenteration of the orbit or radiation treatment to the growing facial
      skeleton. That was possible due to excision of the residual tumor in a second
      step, leading to down-staging of the RMS.

PMID- 20143117
TI  - Depth sensitivity analysis of functional near-infrared spectroscopy measurement
      using three-dimensional Monte Carlo modelling-based magnetic resonance imaging.
AB  - Theoretical analysis of spatial distribution of near-infrared light propagation
      in head tissues is very important in brain function measurement, since it is
      impossible to measure the effective optical path length of the detected signal or
      the effect of optical fibre arrangement on the regions of measurement or its
      sensitivity. In this study a realistic head model generated from structure data
      from magnetic resonance imaging (MRI) was introduced into a three-dimensional
      Monte Carlo code and the sensitivity of functional near-infrared measurement was
      analysed. The effects of the distance between source and detector, and of the
      optical properties of the probed tissues, on the sensitivity of the optical
      measurement to deep layers of the adult head were investigated. The spatial
      sensitivity profiles of photons in the head, the so-called banana shape, and the
      partial mean optical path lengths in the skin-scalp and brain tissues were
      calculated, so that the contribution of different parts of the head to near
      infrared spectroscopy signals could be examined. It was shown that the signal
      detected in brain function measurements was greatly affected by the heterogeneity
      of the head tissue and its scattering properties, particularly for the shorter
      interfibre distances.

PMID- 20143116
TI  - Etanercept-induced anti-Jo-1-antibody-positive polymyositis in a patient with
      rheumatoid arthritis: a case report and review of the literature.
AB  - Antitumor necrosis factor (TNF) therapy has been associated with adverse
      immunologic events including systemic lupus erythematosus. However, the
      development of polymyositis (PM)/dermatomyositis (DM) associated with anti-TNF
      therapy is extremely rare. We experienced a case of a 48-year-old female with
      rheumatoid arthritis (RA) who had anti-Jo-1 antibodies and interstitial lung
      disease but no previous history of PM/DM and who developed PM soon after the
      initiation of etanercept (ETN) therapy for RA. The patient recovered upon
      withdrawal from ETN and corticosteroid (CS) therapies. Only four reports of PM/DM
      associated with anti-TNF therapy for RA could be found in the literature. The
      patients described in three of the four reports were positive for anti-Jo-1
      antibodies before the initiation of anti-TNF therapy, and in all the cases,
      recovery occurred after the cessation of anti-TNF-agent administration and CS
      therapy. These results suggest a relationship between the onset of PM/DM with
      anti-Jo-1 antibody and anti-TNF therapy for RA.

PMID- 20143118
TI  - Molecular characteristics of the Taiwanese multiple drug-resistant ST59 clone of
      Panton-Valentine leucocidin-positive community-acquired methicillin-resistant
      Staphylococcus aureus from pediatric cellulitis.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), which
      often produces Panton-Valentine leucocidin (PVL), has emerged worldwide as a life
      threatening pathogen. Herein, we describe molecular characteristics of MRSA
      isolated from abdominal cellulitis in a 7-year-old Japanese boy. This MRSA was
      PVL-positive and belonged to the Taiwanese multiple drug-resistant CA-MRSA clone
      with the genotype of ST59, staphylococcal cassette chromosome mec (SCCmec) VII
      (SCCmecV, according to recent reclassification), agr1a (a novel agr1 subtype),
      and SaPI (which carried seb1, a newly designated variant seb gene). This study
      demonstrates the first isolation of the Taiwanese PVL-positive ST59 MRSA clone in
      Japan. The data also demonstrate novel subtypes in agr1 and seb and suggest that
      a combination of agr1a, seb1, and PVL could contribute to cellulitis (and its
      recurrence). Recently, a variety of PVL-positive MRSA clones are accumulating in
      Japan.

PMID- 20143119
TI  - A comparative study of anti-inflammatory and antidyslipidemic effects of
      fenofibrate and statins on rheumatoid arthritis.
AB  - We prospectively compared the anti-inflammatory and antidyslipidemic effects of
      fenofibrate and statins in rheumatoid arthritis (RA) patients. Forty-four RA
      patients [male (M) = 7, female (F) = 37] with dyslipidemia were enrolled in this
      6-month study and randomly allocated to the fenofibrate (2 M + 21 F = 23) or
      statins (5 M + 16 F = 21) group. We measured blood chemistry (serum lipid
      profile, sugar, urate, and gamma-glutamyl transpeptidase) and blood pressure 2 h
      after breakfast. Visual analog scale (VAS), C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), and prednisolone (PSL) dosage were also recorded
      immediately before and after the study. Fenofibrate, but not statins,
      significantly decreased serum levels of total cholesterol, low-density
      lipoprotein-cholesterol, and triglycerides (all p < 0.05). A significant
      improvement in VAS was observed in both the fenofibrate group (49.1 +/- 24.7 -->
      14.7 +/- 11.2; p < 0.0001) and the statins group (47.4 +/- 29.7 --> 20.2 +/-
      16.5; p < 0.001). PSL dosage significantly decreased only in the fenofibrate
      group (3.58 +/- 2.68 --> 2.00 +/- 2.22 mg/day; p < 0.01). Significant correlation
      was observed between VAS and CRP in the fenofibrate group (p < 0.05). Fenofibrate
      showed more anti-inflammatory and antidyslipidemic activity than statins in RA.

PMID- 20143120
TI  - Impact of calcifications on patient-specific wall stress analysis of abdominal
      aortic aneurysms.
AB  - As a degenerative and inflammatory desease of elderly patients, about 80% of
      abdominal aortic aneurysms (AAA) show considerable wall calcification. Effect of
      calcifications on computational wall stress analyses of AAAs has been rarely
      treated in literature so far. Calcifications are heterogeneously distributed, non
      fibrous, stiff plaques which are most commonly found near the luminal surface in
      between the intima and the media layer of the vessel wall. In this study, we
      therefore investigate the influence of calcifications as separate AAA
      constituents on finite element simulation results. Thus, three AAAs are
      reconstructed with regard to intraluminal thrombus (ILT), calcifications and
      vessel wall. Each patient-specific AAA is simulated twice, once including all
      three AAA constituents and once neglecting calcifications as it is still common
      in literature. Parameters for constitutive modeling of calcifications are thereby
      taken from experiments performed by the authors, showing that calcifications
      exhibit an almost linear stress-strain behavior with a Young's modulus E >= 40
      MPa. Simulation results show that calcifications exhibit significant load-bearing
      effects and reduce stress in adjacent vessel wall. Average stress within the
      vessel wall is reduced by 9.7 to 59.2%. For two out of three AAAs, peak wall
      stress decreases when taking calcifications into consideration (8.9 and 28.9%).
      For one AAA, simulated peak wall stress increases by 5.5% due to stress peaks
      near calcification borders. However, such stress singularities due to sudden
      stiffness jumps are physiologically doubtful. It can further be observed that
      large calcifications are mostly situated in concavely shaped regions of the AAA
      wall. We deduce that AAA shape is influenced by existent calcifications, thus
      crucial errors occur if they are neglected in computational wall stress analyses.
      A general increase in rupture risk for calcified AAAs is doubted.

PMID- 20143121
TI  - Using PACS audit data for process improvement.
AB  - Today, all types of data are used in various ways to provide useful information.
      PACS Audit data have not been typically used as a data source although it
      includes information that can be used for various purposes such as process
      improvement (PI). In a typical radiology workflow, examinations do not show up on
      a radiologist's unread worklist until the examination has been verified. An issue
      with clinical access to radiology reports was determined to be partly due to
      delays in the verification step. A PI goal was created to reduce this wait time.
      PACS audit data were mined using an in-house application to provide workflow time
      span information, and the particular span from arrived to verified was measured.
      The report also allowed specific examinations and users to be identified, and
      these data were used as a PI educational tool. The end result was a dramatic
      reduction in examinations taking longer than 1 h to be verified which reduced the
      time for report production and enhanced patient care.

PMID- 20143122
TI  - Severity of unhealthy alcohol consumption in medical inpatients and the general
      population: is the general hospital a suitable place for brief interventions?
AB  - OBJECTIVES: Evidence for brief interventions in general hospital (GH) settings is
      scarce, probably due to higher rates of dependent drinkers. The present study
      aims to compare unhealthy drinking patterns in GH patients with the general
      population (GP). METHODS: Sample 1 consisted of 4,075 individuals randomly drawn
      from registration office files, representing the non-institutionalised GP of a
      northern mixed rural-urban German area. Sample 2 consisted of 2,949 consecutively
      admitted patients from a GH covering the same area. RESULTS: Compared to
      individuals from the GP, GH patients revealed higher prevalence rates of alcohol
      dependence (1.3 vs. 5.5%) and alcohol abuse (1.2 vs. 2.8%), but did not differ
      significantly concerning at-risk drinking (5.1 vs. 6.2%). Multinomial logistic
      regression analysis controlling for age, sex and smoking using unrisky alcohol
      consumption as reference category belonging to the GH group was predictive for
      alcohol use disorders but not for at-risk drinking. CONCLUSION: Data show that a
      substantial number of individuals with unhealthy drinking patterns without
      alcohol use disorders can easily be accessed in GH settings if appropriate
      screening measures are conducted.

PMID- 20143123
TI  - Self-rated health and mortality: gender- and age-specific contributions of
      explanatory factors in South Korea.
AB  - OBJECTIVES: This study explored gender- and age-specific contributions of
      explanatory factors to the relationship between self-rated health (SRH) and all
      cause mortality. METHODS: We used mortality follow-up data from 1998 and 2001
      National Health and Nutrition Examination Surveys of South Korea (n = 9,663).
      Explanatory factors included baseline health status, socioeconomic status, health
      behaviors, clinical risk factors, psychosocial factors, and family medical
      history. RESULTS: The ability of explanatory factors to explain the SRH-mortality
      relationship differed with age. For those aged 30-64, most excess hazards were
      explained by all explanatory factors. However, a large part of the mortality
      differentials by SRH remained unexplained among elderly samples. CONCLUSIONS: A
      wide range of health-related factors could explain the SRH-mortality association
      in younger population but not in older population. Factors to explain a large
      part of mortality differentials by SRH among older population should be
      identified.

PMID- 20143124
TI  - Effects of time-varying exposures adjusting for time-varying confounders: the
      case of alcohol consumption and risk of incident human immunodeficiency virus
      infection.
AB  - OBJECTIVE: Discuss issues related to time-varying exposures using as an example
      the recently meta-analyzed literature (Baliunas et al. in Int J Public Health,
      2009) on alcohol consumption and risk of HIV infection. METHODS: Cataloged
      sources of bias and imprecision in the context of time-varying exposures.
      RESULTS: Confounding, selection, or measurement bias may occur when standard
      regression approaches are used to estimate effects of time-varying exposures. The
      reviewed literature on alcohol consumption and HIV infection suffer from one or
      more of these biases. CONCLUSIONS: Detailed prospective data and thoughtful
      implementation of appropriate statistical methods are needed to obtain unbiased
      estimates of time-varying exposures, such as alcohol consumption.

PMID- 20143125
TI  - Barriers to a healthy lifestyle among obese adolescents: a qualitative study from
      Iran.
AB  - PURPOSE: Existing data show a rising prevalence of overweight and obesity among
      Iranian adolescents. The current study investigates adolescents' perceptions
      regarding overweight/obesity and explores barriers to a healthy life style among
      Iranian adolescents. METHODS: A grounded theory approach was used for analyzing
      the participants' experiences, and their perceptions. To collect data, semi
      structured focus group discussions and in-depth interviews were conducted with 51
      adolescents (27 girls and 24 boys), aged 15-17 years, who were either overweight
      or obese. Qualitative content analysis of the data was conducted manually and
      differences in coding were resolved via discussion by four independent reviewers.
      RESULTS: Two main barriers, personal and environmental emerged from data
      analysis. Positive perception of condition, priority of studying, lack of
      willingness, unsatisfactory results, low self-esteem, and perceived lack of
      control were the major personal barriers while lack of family and cultural
      support, inadequate education and scarcity of resources were the common
      environmental barriers to adolescents' healthy lifestyles. CONCLUSIONS: Findings
      demonstrated the main personal and environmental barriers for a healthy life
      style as perceived by adolescents. Understanding these barriers might contribute
      to existing literature by providing evidence from a different culture, and help
      to design effective preventive strategies, and implement appropriate
      interventions.

PMID- 20143126
TI  - Housing and health promotion: moving forward.

PMID- 20143127
TI  - Mortality rates differ among amphibian populations exposed to three strains of a
      lethal ranavirus.
AB  - Infectious diseases are a growing threat to biodiversity, in many cases because
      of synergistic effects with habitat loss, environmental contamination, and
      climate change. Emergence of pathogens as new threats to host populations can
      also arise when novel combinations of hosts and pathogens are unintentionally
      brought together, for example, via commercial trade or wildlife relocations and
      reintroductions. Chytrid fungus (Batrachochytrium dendrobatidis) and amphibian
      ranaviruses (family Iridoviridae) are pathogens implicated in global amphibian
      declines. The emergence of disease associated with these pathogens appears to be
      at least partly related to recent translocations over large geographic distances.
      We experimentally examined the outcomes of novel combinations of host populations
      and pathogen strains using the amphibian ranavirus Ambystoma tigrinum virus (ATV)
      and barred tiger salamanders (Ambystoma mavortium, formerly considered part of
      the Ambystoma tigrinum complex). One salamander population was highly resistant
      to lethal infections by all ATV strains, including its own strain, and mortality
      rates differed among ATV strains according to salamander population. Mortality
      rates in novel pairings of salamander population and ATV strain were not
      predictable based on knowledge of mortality rates when salamander populations
      were exposed to their own ATV strain. The underlying cause(s) for the differences
      in mortality rates are unknown, but local selection pressures on salamanders,
      viruses, or both, across the range of this widespread host-pathogen system are a
      plausible hypothesis. Our study highlights the need to minimize translocations of
      amphibian ranaviruses, even among conspecifc host populations, and the importance
      of considering intraspecific variation in endeavors to manage wildlife diseases.

PMID- 20143128
TI  - Biphasic paraneoplastic brainstem encephalitis associated with anti-Ri antibody.
AB  - Brainstem encephalitis is not a classic paraneoplastic syndrome and usually
      involves monophasic neurological deterioration and has negative magnetic
      resonance imaging (MRI) findings. We describe a patient with brainstem
      encephalitis who had elevated anti-Ri antibody levels and double-step
      neurological deterioration associated with different abnormal lesions on MRI.
      Immunosuppression with steroids and intravenous immune globulin combined with
      aggressive treatment of the tumor successfully led to the resolution of brainstem
      symptoms and MRI lesions. In patients with unusual signs and symptoms of
      paraneoplastic encephalitis mimicking multiple sclerosis, onconeural antibody
      studies are recommended.

PMID- 20143129
TI  - Editing of accD and ndhF chloroplast transcripts is partially affected in the
      Arabidopsis vanilla cream1 mutant.
AB  - The vanilla cream1 (vac1) albino mutant is defective in a gene encoding a
      chloroplast-localized pentatricopeptide repeat protein of the DYW subgroup.
      However, the carboxyl-terminal DYW motif is truncated in VAC1. To identify vac1
      specific phenotypes, we compared 34 chloroplast RNA editing sites and
      approximately 90 chloroplast gene expression patterns among wild type, vac1 and
      another albino mutant ispH, which is defective in the plastid isoprenoid
      biosynthesis pathway. We found that the editing of accD and ndhF transcripts is
      partially affected in vac1. In addition, steady-state levels of chloroplast rRNAs
      are significantly decreased in vac1. The expression of plastid-encoded RNA
      polymerase transcribed genes is down-regulated, whereas the expression of nucleus
      encoded RNA polymerase transcribed genes is up-regulated in vac1. Although the
      development and function of mutant chloroplasts are severely impaired, steady
      state mRNA levels of nucleus-encoded photosynthetic genes are not affected or are
      only slightly decreased in vac1. The ZAT10 gene encodes a transcription factor
      and its expression is down-regulated by norflurazon treatment in wild type. This
      norflurazon effect was not observed in vac1. These results suggest that the VAC1
      protein may be involved in plastid-to-nucleus retrograde signaling in addition to
      its role in chloroplast RNA editing and gene expression. A defect in a key
      biosynthetic pathway can have many indirect effects on chloroplast gene
      expression as is seen in the ispH mutant. Similarly, the vac1 mutant has
      pleiotropic molecular phenotypes and most of which may be indirect effects.

PMID- 20143130
TI  - Gene expression of DAM5 and DAM6 is suppressed by chilling temperatures and
      inversely correlated with bud break rate.
AB  - We previously identified a cluster of d ormancy-a ssociated M ADS-box
      transcription factors (DAM genes) in peach [Prunus persica (L.) Batsch] as
      potential candidates for control of the non-dormant phenotype observed in the evg
      mutant. Of these genes, DAM3, DAM5 and DAM6 were winter expressed, suggesting a
      role for these genes during endodormancy. We used peach cultivars with
      contrasting chilling requirements (CR) for bud break to observe the expression of
      DAM3, DAM5 and DAM6 in response to chilling accumulation in the field and
      controlled environments. Vegetative terminal and floral buds were sampled weekly
      from field grown 'Contender' (1050 h CR), 'Rubyprince' (850 h CR) and
      'Springprince' (650 h CR) peach cultivars through winter 2008-2009. Flower and
      vegetative terminal bud break potential was evaluated at each sampling by forcing
      cuttings in a growth-permissive environment. We also measured vegetative terminal
      bud break and DAM gene expression in potted 'Contender' and 'Peen-To' (450 h CR)
      trees under controlled-environment cold exposure. DAM3, DAM5 and DAM6 are all
      suppressed by exposure to chilling temperatures in the field and in controlled
      conditions. Expression of DAM5 and DAM6 are higher in high chill cultivars prior
      to chilling accumulation and their expression level reaches a minimum in each
      cultivar coincident with acquisition of bud break competence. Expression levels
      of DAM5 and DAM6 in vegetative tips in controlled environment conditions were
      negatively correlated with the time required for bud break in forcing conditions.
      The expression patterns of DAM5 and DAM6 are consistent with a role as
      quantitative repressors of bud break.

PMID- 20143131
TI  - Modeling prostate cancer: a perspective on transgenic mouse models.
AB  - Despite considerable success in treatment of early stage localized prostate
      cancer (PC), acute inadequacy of late stage PC treatment and its inherent
      heterogeneity poses a formidable challenge. Clearly, an improved understanding of
      PC genesis and progression along with the development of new targeted therapies
      are warranted. Animal models, especially, transgenic immunocompetent mouse
      models, have proven to be the best ally in this respect. A series of models have
      been developed by modulation of expression of genes implicated in cancer-genesis
      and progression; mainly, modulation of expression of oncogenes, steroid hormone
      receptors, growth factors and their receptors, cell cycle and apoptosis
      regulators, and tumor suppressor genes have been used. Such models have
      contributed significantly to our understanding of the molecular and pathological
      aspects of PC initiation and progression. In particular, the transgenic mouse
      models based on multiple genetic alterations can more accurately address the
      inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis
      and progression but also for clinically relevant evaluation of new therapies.
      Further, with advances in conditional knockout technologies, otherwise
      embryonically lethal gene changes can be incorporated leading to the development
      of new generation transgenics, thus adding significantly to our existing
      knowledge base. Different models and their relevance to PC research are
      discussed.

PMID- 20143132
TI  - Soil arsenic surveys of New Orleans: localized hazards in children's play areas.
AB  - Arsenic (As) ranks first on the 2005 and 2007 hazardous substances priority lists
      compiled for the Comprehensive Environmental Response, Compensation, and
      Liability Act (CERCLA). This study describes two New Orleans soil As surveys: (1)
      a survey of composite soil samples from 286 census tracts and (2) a field survey
      of soil As at 38 play areas associated with the presence of chromated-copper
      arsenate (CCA)-treated wood on residential and public properties. The survey of
      metropolitan New Orleans soils revealed a median As content of 1.5 mg/kg (range
      <0.2-16.4) and no distinctive differences between the soils of the city core and
      outlying areas. Play area accessible soils associated with CCA-treated wood (N =
      32) had a median As of 57 mg/kg and 78% of the samples were >=12 mg/kg, the
      Louisiana soil As standard. The field survey of play areas for CCA-treated wood
      (N = 132 samples at 38 sites) was conducted with a portable energy-dispersive X
      ray fluorescence (XRF) analyzer. Seventy-five of 132 wood samples (56.8%) were
      deemed CCA-treated wood. Of the 38 play areas surveyed, 14 (36.8%) had CCA
      treated wood. A significant association (Fisher's exact p-value = 0.348 * 10(-6))
      was found between CCA-treated wood and soil As (N = 75). At one elementary school
      CCA-treated woodchips (As range 813-1,654 mg As/kg) covered the playgrounds. The
      situation in New Orleans probably exists in play areas across the nation. These
      findings support a precautionary program for testing soils and wood for hazardous
      substances at all play areas intended for children.

PMID- 20143133
TI  - Characterization of zebrafish Esrom (Myc-binding protein 2) RCC1-like domain
      splice variants.
AB  - PHR protein family consists of C. elegan Rpm-1/Drosophila Highwire/Zebrafish
      Esrom/Mouse Phr-1/Human Pam. Esrom is required for correct neurites exiting the
      paused state at intermediate targets as well as pteridine synthesis. This study
      reports the identification and characterization of two novel Esrom splice
      variants, named splice variants 2 (splicing out 5' 24 bp of exon 17) and 3
      (splicing out 5' 24 bp of exons 17 and 18). Polypeptides encoded by 5' 24 bp of
      exons 17 and 18 are part of basic amino-acid-rich region inside Esrom RCC1-like
      domain (RLD). These two splice variants maintain the whole protein reading frame
      and alternative exons usage patterns are conserved with mammal. At different
      developmental stages and adult zebrafish tissues, abundances of these splice
      variants are different. Importantly, by yeast two-hybrid screen and confocal
      colocalization analysis, it was found that alternative splicing of exon 18
      regulates Esrom RLD interaction with kinesin family member 22 and G protein beta
      subunit 1. Taken together, these results suggest that Esrom RLD functions are
      regulated by alternative splicing at temporal and spatial-specific manner.

PMID- 20143134
TI  - Dexamethasone electrically controlled release from polypyrrole-coated
      nanostructured electrodes.
AB  - One of the key challenges to engineering neural interfaces is to reduce their
      immune response toward implanted electrodes. One potential approach to minimize
      or eliminate this undesired early inflammatory tissue reaction and to maintain
      signal transmission quality over time is the delivery of anti-inflammatory
      biomolecules in the vicinity of the implant. Here, we report on a facile and
      reproducible method for the fabrication of high surface area nanostructured
      electrodes coated with an electroactive polymer, polypyrrole (PPy) that can be
      used to precisely release drug by applying an electrical stimuli. The method
      consists of the electropolymerization of PPy incorporated with drug,
      dexamethasone (DEX), onto a brush of metallic nanopillars, obtained by
      electrodeposition of the metal within the nanopores of gold-coated polycarbonate
      template. The study of the release of DEX triggered by electrochemical stimuli
      indicates that the system is a true electrically controlled release system.
      Moreover, it appears that the presence of metallic nanowires onto the electrode
      surface improves the adherence between the polymer and the electrode and
      increases the electroactivity of the PPy coating.

PMID- 20143135
TI  - Electrochemical behaviour of Ti-Ni SMA and Co-Cr alloys in dynamic Tyrode's
      simulated body fluid.
AB  - The electrochemical behaviour of Ti-Ni shape memory alloy and Co-Cr alloys were
      investigated in dynamic Tyrode's simulated body fluid on a Model CP6
      Potentiostat/Galvanostat. The results indicated that, for all alloys, the anodic
      dissolution and the pitting sensitivity increased with the flow rate of the
      Tyrode's solution increasing while the open-circuit potentials and pitting
      corrosion potentials decreased with the Tyrode's solution increasing. Pitting
      corrosion of Ti-Ni alloy was easier than Co-Cr alloys. Since the solution's flow
      enhanced oxygen transform and made it easy to reach the surface of electrodes,
      the plateau of oxygen diffusion control was diminished. All these indicated that
      the cathodic reduction and the corrosion reaction, which was controlled by the
      electrochemical mass transport process, were all accelerated in dynamic Tyrode's
      simulated body fluid.

PMID- 20143136
TI  - A 'metastasis-prone' signature for early-stage mismatch-repair proficient
      sporadic colorectal cancer patients and its implications for possible
      therapeutics.
AB  - Metastasis is the major cause of cancer mortality. We aimed to find a metastasis
      prone signature for early stage mismatch-repair proficient sporadic colorectal
      cancer (CRC) patients for better prognosis and informed use of adjuvant
      chemotherapy. The genome-wide expression profiles of 82 age-, ethnicity- and
      tissue-matched patients and healthy controls were analyzed using the Affymetrix
      U133 Plus 2 array. Metastasis-negative patients have 5 years or more of follow
      up. A 10 x 10 two-level nested cross-validation design was used with several
      families of classification models to identify the optimal predictor for
      metastasis. The best classification model yielded a 54 gene-set (74 probe sets)
      with an estimated prediction accuracy of 71%. The specificity, sensitivity,
      negative and positive predictive values of the signature are 0.88, 0.58, 0.84 and
      0.65, respectively, indicating that the gene-set can improve prognosis for early
      stage sporadic CRC patients. These 54 genes, including node molecules YWHAB,
      MAP3K5, LMNA, APP, GNAQ, F3, NFATC2, and TGM2, integrate multiple bio-functions
      in various compartments into an intricate molecular network, suggesting that cell
      wide perturbations are involved in metastasis transformation. Further, querying
      the ;Connectivity Map' with a subset (70%) of these genes shows that Gly-His-Lys
      and securinine could reverse the differential expressions of these genes
      significantly, suggesting that they have combinatorial therapeutic effect on the
      metastasis-prone patients. These two perturbagens promote wound-healing,
      extracellular matrix remodeling and macrophage activation thus highlighting the
      importance of these pathways in metastasis suppression for early-stage CRC.

PMID- 20143137
TI  - Reduced photosynthetic activity is directly correlated with 2-(3H)
      benzoxazolinone accumulation in lettuce leaves.
AB  - 2-(3H)-benzoxazolinone (BOA) is a secondary plant metabolite previously found to
      inhibit plant growth and development. The phytotoxic activity of BOA has been
      extensively demonstrated over the last years. However, the relation of BOA
      phytotoxicity with BOA accumulation in plant leaves has not been thoroughly
      investigated. In this work, BOA phytotoxicity on photosynthesis (PhiPSII and Pn)
      of lettuce (Lactuca sativa L. cv. Great Lakes) was studied, and these results
      were correlated with BOA quantities in the leaves. BOA-treated plants showed
      reduced photosynthesis rate 6 h after the beginning of the treatment, and the
      efficiency of photosystem II started to be affected 10 h after treatment. These
      results were correlated with an increasing concentration of BOA in leaves that
      starts 6 h after treatment and shows a maximum at 96 h.

PMID- 20143138
TI  - Epigenetic modifications in 3D: nuclear organization of the differentiating
      mammary epithelial cell.
AB  - During the development of tissues, complex programs take place to reach
      terminally differentiated states with specific gene expression profiles.
      Epigenetic regulations such as histone modifications and chromatin condensation
      have been implicated in the short and long-term control of transcription. It has
      recently been shown that the 3D spatial organization of chromosomes in the
      nucleus also plays a role in genome function. Indeed, the eukaryotic interphase
      nucleus contains sub-domains that are characterized by their enrichment in
      specific factors such as RNA Polymerase II, splicing machineries or
      heterochromatin proteins which render portions of the genome differentially
      permissive to gene expression. The positioning of individual genes relative to
      these sub-domains is thought to participate in the control of gene expression as
      an epigenetic mechanism acting in the nuclear space. Here, we review what is
      known about the sub-nuclear organization of mammary epithelial cells in
      connection with gene expression and epigenetics. Throughout differentiation,
      global changes in nuclear architecture occur, notably with respect to
      heterochromatin distribution. The positions of mammary-specific genes relative to
      nuclear sub-compartments varies in response to hormonal stimulation. The
      contribution of tissue architecture to cell differentiation in the mammary gland
      is also seen at the level of nuclear organization, which is sensitive to
      microenvironmental stimuli such as extracellular matrix signaling. In addition,
      alterations in nuclear organization are concomitant with immortalization and
      carcinogenesis. Thus, the fate of cells appears to be controlled by complex
      pathways connecting external signal integration, gene expression, epigenetic
      modifications and chromatin organization in the nucleus.

PMID- 20143139
TI  - Social capital and glucose control.
AB  - There is a growing diabetes epidemic in the United States and if we are to halt
      its progress we need to better understand the social determinants of this disease
      and its control. Social capital, which has been associated with general health
      and mortality, may be one important mediator of glucose control. In this study we
      determine if neighborhood social capital is associated with glucose control,
      independent of individual factors. We performed a cross-sectional study of Black
      veterans with diabetes living in Philadelphia. We merged individual-level data
      from surveys and charts with six area-level social capital descriptors. Holding
      all other variables constant, patients who lived in neighborhoods that scored
      near the 5th percentile of working together to improve the neighborhood were
      estimated to have glycosylated hemoglobin (HbA1c) values that were at least one
      point above a conservative clinical definition of "diabetes control" (HbA1c <=
      8%). If these same patients were to live in neighborhoods in the 95th percentile,
      their expected HbA1c would be over 1/2 a point below the cut-off value 8%. No
      other measure of social capital was associated with HbA1c. In this study of black
      veterans with diabetes we observed that living in neighborhoods where people work
      together is associated with better glucose control.

PMID- 20143140
TI  - Attributions of blame and responsibility in sexual harassment: reexamining a
      psychological model.
AB  - Kelley's (Nebr Symp Motiv 15:192-238, 1967) attribution theory can inform sexual
      harassment research by identifying how observers use consensus, consistency, and
      distinctiveness information in determining whether a target or perpetrator is
      responsible for a sexual harassment situation. In this study, Kelley's theory is
      applied to a scenario in which a male perpetrator sexually harasses a female
      target in a university setting. Results from 314 predominantly female college
      students indicate that consistency and consensus information significantly affect
      participants' judgments of blame and responsibility for the situation. The
      authors discuss the importance of the reference groups used to derive consensus
      and distinctiveness information, and reintroduce Kelley's attribution theory as a
      means of understanding observers' perceptions of sexual harassment.

PMID- 20143141
TI  - Role of intrapulmonary expression of inducible nitric oxide synthase gene and
      nuclear factor kappaB activation in severe pancreatitis-associated lung injury.
AB  - The aim of this study is to explore the relationship of intrapulmonary activation
      of nuclear factor-kappaB (NF-kappaB) and the expression of inducible nitric oxide
      synthase (iNOS) mRNA with pulmonary injury in rats with severe acute pancreatitis
      (SAP). Fifty-four Sprague Dawley rats were randomly divided into three groups:
      sham operation (control) group (n = 18), SAP group (n = 18), and pyrrolindine
      dithiocarbamate (PDTC) pretreated group (n = 18). A SAP model was induced by
      retrograde injected 5% sodium taurocholate into the bile-pancreatic duct (1
      ml/kg). PDTC-pretreated SAP rats were given 100 mg/kg body weight PDTC
      intraperitoneally before pancreatitis was induced. Six rats from each group were
      sacrificed at 3, 6, and 12 h after modeling. Activation of NF-kappaB in pulmonary
      tissues and pancreas tissues was detected by immunohistochemical methods.
      Intrapulmonary expression of iNOSmRNA was assayed by fluorogenic quantitative
      reverse transcription polymerize chain reaction. The expression of NF-kappaB in
      the SAP group in pulmonary tissues was enhanced significantly at any measure
      point compared with control group (58.4 +/- 10.8 vs. 3.8 +/- 1.8, 119.8 +/- 17.8
      vs. 5.2 +/- 2.4, and 90.2 +/- 14.4 vs. 4.7 +/- 2.2, P < 0.01). But the
      expressions of NF-kappaB in the PDTC group were significantly lower than those in
      SAP group (54.3 +/- 9.6 vs. 58.4 +/- 10.8, 93.9 +/- 7.9 vs. 119.8 +/- 17.8, and
      82.2 +/- 13.3 vs. 90.2 +/- 14.4, P < 0.05). The number of positive cells in SAP
      group and PDTC group reached its peak at 6 h and then declined. The expression of
      iNOSmRNA in PDTC groups was significantly weaker than that in SAP group (2.0 +/-
      0.8 vs. 2.2 +/- 1.9, 2.4 +/- 1.2 vs. 4.6 +/- 1.8, and 1.5 +/- 0.8 vs. 3.2 +/-
      1.5, P < 0.05). The activation of NF-kappaB may be involved in the SAP lung
      injury through regulating the expression of iNOSmRNA. PDTC might inhibit the
      activation of NF-kappaB and then reduce the expression of iNOSmRNA and
      effectively alleviate the severity of lung injury.

PMID- 20143142
TI  - Predicting stimulus-locked single unit spiking from cortical local field
      potentials.
AB  - The rapidly increasing use of the local field potential (LFP) has motivated
      research to better understand its relation to the gold standard of neural
      activity, single unit (SU) spiking. We addressed this in an in vivo, awake,
      restrained mouse auditory cortical electrophysiology preparation by asking
      whether the LFP could actually be used to predict stimulus-evoked SU spiking.
      Implementing a Bayesian algorithm to predict the likelihood of spiking on a trial
      by trial basis from different representations of the despiked LFP signal, we were
      able to predict, with high quality and fine temporal resolution (2 ms), the time
      course of a SU's excitatory or inhibitory firing rate response to natural species
      specific vocalizations. Our best predictions were achieved by representing the
      LFP by its wide-band Hilbert phase signal, and approximating the statistical
      structure of this signal at different time points as independent. Our results
      show that each SU's action potential has a unique relationship with the LFP that
      can be reliably used to predict the occurrence of spikes. This "signature"
      interaction can reflect both pre- and post-spike neural activity that is
      intrinsic to the local circuit rather than just dictated by the stimulus.
      Finally, the time course of this "signature" may be most faithful when the full
      bandwidth of the LFP, rather than specific narrow-band components, is used for
      representation.

PMID- 20143143
TI  - Geometry and dynamics of activity-dependent homeostatic regulation in neurons.
AB  - To maintain activity in a functional range, neurons constantly adjust membrane
      excitability to changing intra- and extracellular conditions. Such activity
      dependent homeostatic regulation (ADHR) is critical for normal processing of the
      nervous system and avoiding pathological conditions. Here, we posed a homeostatic
      regulation problem for the classical Morris-Lecar (ML) model. The problem was
      motivated by the phenomenon of the functional recovery of stomatogastric neurons
      in crustaceans in the absence of neuromodulation. In our study, the regulation of
      the ionic conductances in the ML model depended on the calcium current or the
      intracellular calcium concentration. We found an asymptotic solution to the
      problem under the assumption of slow regulation. The solution provides a full
      account of the regulation in the case of correlated or anticorrelated changes of
      the maximal conductances of the calcium and potassium currents. In particular,
      the solution shows how the target and parameters of the regulation determine
      which perturbations of the conductances can be compensated by the ADHR. In some
      cases, the sets of compensated initial perturbations are not convex. On the basis
      of our analysis we formulated specific questions for subsequent experimental and
      theoretical studies of ADHR.

PMID- 20143144
TI  - Scalar inferences in Autism Spectrum Disorders.
AB  - On being told "John or Mary will come", one might infer that not both of them
      will come. Yet the semantics of "or" is compatible with a situation where both
      John and Mary come. Inferences of this type, which enrich the semantics of "or"
      from an 'inclusive' to an 'exclusive' interpretation, have been extensively
      studied in linguistic pragmatics. However, the phenomenon has not been much
      explored in Autism Spectrum Disorders (ASDs), where pragmatic deficits are
      commonly reported. Here, we present an experiment investigating these inferences.
      We predicted that, as a result of the reported pragmatic deficits, participants
      with ASD would produce fewer inferential enrichments of "or" than matched
      controls. However, contrary to expectations, but in line with recent findings by
      Pijnacker et al. (Journal of Autism and Developmental Disorders, 39, 607-618,
      2009), performances did not differ across groups. This unexpected finding is
      discussed in light of the literature on pragmatic abilities in autism.

PMID- 20143145
TI  - Parent, teacher, and self perceptions of psychosocial functioning in
      intellectually gifted children and adolescents with autism spectrum disorder.
AB  - Parent, teacher, and self-perceptions of 54 high ability students with autism
      spectrum disorder (ASD) were assessed through administration of the Behavioral
      Assessment Scales for Children, Second Edition. Parent reports resulted in
      clinically elevated scores on the Atypicality, Attention Problems, Depression,
      Hyperactivity, Withdrawal, Activities of Daily Living, Adaptability, and Social
      Skills subscales, and teacher reports resulted in clinically elevated scores on
      the Atypicality, Depression, Withdrawal, and Adaptability subscales. Self-report
      scores were in the average range. Parents and teachers of adolescents reported
      greater adaptability and fewer symptoms of atypicality than parents and teachers
      of children. Psychosocial functioning appears impacted in high ability students
      with ASD and developmental differences in severity may exist.

PMID- 20143146
TI  - Anxiety symptoms in boys with autism spectrum disorder, attention-deficit
      hyperactivity disorder, or chronic multiple tic disorder and community controls.
AB  - We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety
      disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention
      deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD
      plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community
      Controls. Anxiety symptoms were assessed using parent and teacher versions of a
      DSM-IV-referenced rating scale. All three groups of boys with co-morbid ADHD
      evidenced more severe anxiety than Controls. Group differences in anxiety varied
      as a function of symptom, disorder, informant, and co-morbidity supporting the
      notion that co-morbid neurobehavioral syndromes differentially impact clinical
      features of co-occurring anxiety symptoms. Findings also suggest that GAD and SAD
      are phenomenologically unique, even in children with ASD. Implications for
      nosology are discussed.

PMID- 20143147
TI  - Comparison of short and long versions of the Prudhoe Cognitive Function Test and
      the K-BIT in participants with intellectual impairment.
AB  - The Prudhoe Cognitive Function Test (PCFT) directly measures the cognitive
      abilities of people with intellectual impairment. This study examined the
      relationship between this instrument and the Kaufman Brief Intelligence Test (K
      BIT) and two shorter versions of the same scale. High correlations between the
      verbal and performance sections of the K-BIT and the Long PCFT were found with
      correlation coefficients of 0.85 and 0.78, respectively. Extremely high
      correlations between the Short versions of the PCFT and the Long version were
      obtained at 0.97 for Form A and 0.98 for Form B, illustrating that both Short
      forms and the Long form are essentially interchangeable. The PCFT is a reliable
      and robust schedule in the assessment of cognitive function in this population.

PMID- 20143148
TI  - Dysregulated sexuality and high sexual desire: distinct constructs?
AB  - The literature on dysregulated sexuality, whether theoretical, clinical or
      empirical, has failed to differentiate the construct from high sexual desire. In
      this study, we tested three hypotheses which addressed this issue. A sample of
      6458 men and 7938 women, some of whom had sought treatment for sexual
      compulsivity, addiction or impulsivity, completed an online survey comprised of
      various sexuality measures. Men and women who reported having sought treatment
      scored significantly higher on measures of dysregulated sexuality and sexual
      desire. For men, women, and those who had sought treatment, dysregulated
      sexuality was associated with increased sexual desire. Confirmatory factor
      analysis supported a one-factor model, indicating that, in both male and female
      participants, dysregulated sexuality and sexual desire variables loaded onto a
      single underlying factor. The results of this study suggest that dysregulated
      sexuality, as currently conceptualized, labelled, and measured, may simply be a
      marker of high sexual desire and the distress associated with managing a high
      degree of sexual thoughts, feelings, and needs.

PMID- 20143149
TI  - Organizational adaptation: bridging the research to practice gap.
AB  - Currently, the children's mental health system appears dysfunctional and in need
      of serious attention. A possible remedy for this disarray would be for
      researchers and providers to establish integrated management systems which
      include mutual, cross organizational learning, and reciprocal feedback
      mechanisms. This type of adaptive co-management to organizational governance
      would fully integrate research and practice at the community level. Using a
      public health service model, this organizational management approach to research
      and practice would harvest diverse scientific knowledge and disseminate that
      knowledge through the natural occurring culture and practice of each community.
      Organizational and clinical knowledge acquisition, as well as practice
      improvements would necessarily occur over time and across institutions.

PMID- 20143150
TI  - Improving the mental health of children in child welfare through the
      implementation of evidence-based parenting interventions.
AB  - Any comprehensive approach to children's mental health should consider services
      systems such as Child Welfare that provide services to children with high rates
      of emotional and behavioral disorders. This paper will review what is known about
      efficacious parent-focused interventions that can improve the lives of children
      in Child Welfare and explore possible reasons why such interventions are rarely
      used by Child Welfare agencies. Data from a pilot study suggest key features for
      increasing the implementation of efficacious practices to improve children's
      mental health.

PMID- 20143151
TI  - MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta
      analysis involving 15,260 cases and 20,411 controls.
AB  - Published data on the association between MTHFR C677T polymorphism and breast
      cancer risk are inconclusive. To derive a more precise estimation of the
      relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of
      Science were searched. Crude ORs with 95% CIs were used to assess the strength of
      association between the MTHFR C677T polymorphism and breast cancer risk. The
      pooled ORs were performed with co-dominant model (CT vs. CC, TT vs. CC), dominant
      model (CT + TT vs. CC), and recessive model (TT vs. CC + CT), respectively. A
      total of 37 studies including 15,260 cases and 20,411 controls were involved in
      this meta-analysis. Overall, significantly elevated breast cancer risk was
      associated with TT variant genotype in homozygote comparison and dominant genetic
      model when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.11,
      95% CI = 1.01-1.23; dominant model: OR = 1.04, 95% CI = 1.00-1.09). In the
      subgroup analysis by ethnicity, significantly increased risks were found for TT
      allele carriers among Asians (TT vs. CC: OR = 1.18, 95% CI = 1.04-1.35; recessive
      model: OR = 1.15, 95% CI = 1.03-1.29). When stratified by study design,
      statistically significantly elevated risk was found in hospital-based studies (TT
      vs. CC: OR = 1.18, 95% CI = 1.02-1.38; recessive model: OR = 1.17, 95% CI = 1.05
      1.29). In the subgroup analysis by menopausal status, statistically significantly
      increased risk was found among postmenopausal women (CT vs. CC: OR = 1.12, 95% CI
      = 1.02-1.23; dominant model: OR = 1.11, 95% CI = 1.01-1.22). In conclusion, this
      meta-analysis suggests that the MTHFR T allele is a low-penetrant risk factor for
      developing breast cancer.

PMID- 20143152
TI  - TGFB1 L10P polymorphism is associated with breast cancer susceptibility: evidence
      from a meta-analysis involving 47,817 subjects.
AB  - Published data on the association between TGFB1 L10P polymorphism and breast
      cancer risk are inconclusive. In order to derive a more precise estimation of the
      relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to
      assess the strength of association between them. A total of 30 studies including
      20,401 cases and 27,416 controls were involved in this meta-analysis. Overall,
      significantly elevated breast cancer risk was associated with TGFB1 10P allele
      when all studies were pooled into the meta-analysis (LP vs. LL: OR = 1.046, 95%
      CI = 1.003-1.090; dominant model: OR = 1.052, 95% CI = 1.012-1.095). In the
      subgroup analysis by ethnicity, statistically significantly elevated risk was
      found in Caucasians (dominant model: OR = 1.045, 95% CI = 1.001-1.091). When
      stratified by study design, statistically significantly elevated risk was found
      based on population-based studies (dominant model: OR = 1.076, 95% CI = 1.019
      1.136). In conclusion, this meta-analysis suggests that the TGFB1 10P allele may
      be a low-penetrant risk factor for developing breast cancer. However, large
      sample and representative population-based studies with homogeneous breast cancer
      patients and well-matched controls are warranted to confirm this finding.

PMID- 20143153
TI  - Worse prognosis of metaplastic breast cancer patients than other patients with
      triple-negative breast cancer.
AB  - The present study was designed to assess the clinical characteristics and
      outcomes of metaplastic breast cancer (MBC) compared to general invasive ductal
      carcinoma (IDC) and the triple-negative subtype (TN-IDC). The study population
      included 35 MBC and 2,839 IDC patients, including 473 TN-IDC diagnoses, from the
      National Cancer Center, Korea between 2001 and 2008. The clinicopathological
      characteristics and clinical outcomes were retrospectively reviewed. Mean age of
      patients was 47.4 years for the MBC group and 48.3 years for the IDC group. The
      MBC patients presented with a larger tumor size (>/=T2, 74.3% vs. 38.8%, P <
      0.001), more distant metastasis at the first diagnosis (8.6% vs. 2.0%, P = 0.04),
      higher histologic grade (grade 3, 65.7% vs. 41.4%, P < 0.001), fewer estrogen
      receptor (ER), and progesterone receptor (PgR) positivity (ER+, 5.7% vs. 65.4%, P
      < 0.001; PgR+, 8.6% vs. 55.8%, P < 0.001), higher Ki-67 expression (35.5 +/-
      26.2% vs. 20.6 +/- 19.8%, P = 0.024), and more TN subtypes (80.0% vs. 16.7%, P <
      0.001) compared to the IDC group. Fifteen (46.8%) MBC patients and 260 (9.3%) IDC
      patients experienced disease recurrence with a median follow-up of 47.2 months
      (range 4.9-100.6 months). MBC was a poor prognostic factor for disease recurrence
      and overall survival in univariate and multivariate analysis (HR 3.89 in
      recurrence, 95% CI: 1.36-11.14, P = 0.01; HR 5.29 in death, 95% CI: 2.15-13.01, P
      < 0.001). MBC patients also experienced more disease recurrence (HR 3.99, 95% CI:
      1.31-12.19, P = 0.01) and poorer overall survival (HR 3.14, 95% CI: 1.19-8.29, P
      = 0.02) compared to the 473 TN-IDC patients, as reflected by aggressive
      pathological features. Patients with MBC appeared to have inherently aggressive
      tumor biology with poorer clinical outcomes than those with general IDC or TN
      IDC.

PMID- 20143154
TI  - Lack of association between MnSOD Val16Ala polymorphism and breast cancer risk: a
      meta-analysis involving 58,448 subjects.
AB  - Published data on the association between MnSOD Val16Ala polymorphism and breast
      cancer risk are inconclusive. To derive a more precise estimation of the
      relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of
      Science were searched. Crude ORs with 95% CIs were used to assess the strength of
      association between the MnSOD Val16Ala polymorphism and breast cancer risk. The
      pooled ORs were performed for co-dominant model (Val/Ala vs. Val/Val, Ala/Ala vs.
      Val/Val), dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model
      (Ala/Ala vs. Val/Ala + Val/Val), respectively. A total of 32 studies including
      26,022 cases and 32,426 controls were involved in this meta-analysis. Overall, no
      significant associations were found between MnSOD Val16Ala polymorphism and
      breast cancer risk when all studies pooled into the meta-analysis (Val/Ala vs.
      Val/Val: OR = 1.022, 95% CI = 0.981-1.064; Ala/Ala vs. Val/Val: OR = 1.006, 95%
      CI = 0.934-1.083; dominant model: OR = 1.013, 95% CI = 0.962-1.066; and recessive
      model: OR = 0.985, 95% CI = 0.931-1.042). In the subgroup analysis by ethnicity
      or study design, still no significant associations were found for all comparison
      models. In conclusion, this meta-analysis suggests that the MnSOD Val16Ala
      polymorphism may be not associated with breast cancer development. However, large
      sample and representative population-based studies with homogeneous breast cancer
      patients and well-matched controls are warranted to confirm this finding.

PMID- 20143155
TI  - NBS1 8360G > C polymorphism is associated with breast cancer risk: a meta
      analysis.
AB  - NBS1 gene plays an important role in DNA repair. Many epidemiological studies
      have investigated the association between NBS1 8360G > C polymorphism and breast
      cancer, however, the results are still controversial. Therefore, we performed a
      meta-analysis of 10 case-control studies. Crude odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strength of the association.
      The results showed NBS1 8360G > C polymorphism contributed to breast risk in
      overall populations (for CC vs. GG: OR = 0.75, 95% CI = 0.74-0.98, P = 0.13 for
      heterogeneity; for the recessive model CC vs. GG/CG: OR = 0.88, 95% CI = 0.77
      1.00, P = 0.44 for heterogeneity). In subgroup analysis by ethnicity, no
      significant association was found in all genetic models. In summary, our meta
      analysis strongly suggests the NBS1 8360G > C polymorphism is associated with
      breast cancer.

PMID- 20143156
TI  - Purification and properties of digestive lipases from Chinook salmon
      (Oncorhynchus tshawytscha) and New Zealand hoki (Macruronus novaezelandiae).
AB  - Lipases were purified from delipidated pyloric ceca powder of two New Zealand
      sourced fish, Chinook salmon (Oncorhynchus tshawytscha) and hoki (Macruronus
      novaezelandiae), by fractional precipitation with polyethylene glycol 1000,
      followed by affinity chromatography using cholate-Affi-Gel 102, and gel
      filtration on Sephacryl S-300 HR. For the first time, in-polyacrylamide gel
      activity of purified fish lipases against 4-methylumbelliferyl butyrate has been
      demonstrated. Calcium ions and sodium cholate were absolutely necessary both for
      lipase stability in the gel and for optimum activity against caprate and
      palmitate esters of p-nitrophenol. A single protein band was present in native
      polyacrylamide gels for both salmon and hoki final enzyme preparations. Under
      denaturing conditions, electrophoretic analysis revealed two bands of 79.6 and
      54.9 kDa for salmon lipase. It is proposed that these bands correspond to an
      uncleaved and a final form of the enzyme. One band of 44.6 kDa was seen for hoki
      lipase. pI values of 5.8+/-0.1 and 5.7+/-0.1 were obtained for the two salmon
      lipase forms. The hoki lipase had a pI of 5.8+/-0.1. Both lipases had the highest
      activity at 35 degrees C, were thermally labile, had a pH optimum of 8-8.5, and
      were more acid stable compared to other fish lipases studied to date. Both
      enzymes were inhibited by the organophosphate paraoxon. Chinook salmon and hoki
      lipases showed good stability in several water-immiscible solvents. The enzymes
      had very similar amino acid composition to mammalian carboxyl ester lipases and
      one other fish digestive lipase. The salmon enzyme was an overall better catalyst
      based on its higher turnover number (3.7+/-0.3 vs. 0.71+/-0.05 s(-1) for the hoki
      enzyme) and lower activation energy (2.0+/-0.4 vs. 7.6+/-0.8 kcal/mol for the
      hoki enzyme) for the hydrolysis of p-nitrophenyl caprate. The salmon and hoki
      enzymes are homologous with mammalian carboxyl ester lipases.

PMID- 20143157
TI  - High affinity carnitine transporters from OCTN family in neural cells.
AB  - Neurons are known to accumulate L-carnitine--a compound necessary for transfer of
      acyl moieties through biological membranes, apart from very low beta-oxidation of
      fatty acids in adult brain. Present study demonstrates expression of octn2 and
      octn3 genes coding high affinity carnitine transporters, as well as presence of
      both proteins in neurons obtained from suckling and adult rats, and also in mouse
      transformed neural cells. Measurements of carnitine transport show activity of
      both transporters in neural cells, pointing to their importance in physiological
      processes other than beta-oxidation.

PMID- 20143158
TI  - Transportable and non-transportable inhibitors of L-glutamate uptake produce
      astrocytic stellation and increase EAAT2 cell surface expression.
AB  - Astrocytic excitatory amino acid transporters (EAATs) regulate excitatory
      transmission and limit excitotoxicity. Evidence for a functional interface
      between EAATs and glial fibrillary acidic protein (GFAP) relevant to astrocytic
      morphology led to investigations of actions of transportable (D-Aspartate (D-Asp)
      and (2S,3S,4R)-2-(carboxycyclopropyl)glycine (L-CCG-III)) and non-transportable
      (DL-threo-beta-benzyloxyaspartate (DL-TBOA)) inhibitors of Glu uptake in murine
      astrocytes. D-Asp (1 mM), L-CCG-III (0.5 mM) and DL-TBOA (0.5 mM) produced time
      dependent (24-72 h) reductions in (3)[H]D-Asp uptake (approximately 30-70%) with
      little or no gliotoxicity. All drugs induced a profound change in phenotype from
      cobblestone to stellate morphology and image analysis revealed increases in the
      intensity of GFAP immunolabelling for L-CCG-III and DL-TBOA. Cytochemistry
      indicated localized changes in F-actin distribution. Cell surface expression of
      EAAT2, but not EAAT1, was elevated at 72 h. Blockade of Glu uptake by both types
      of EAAT inhibitor exerts longer-term effects on astrocytic morphology and a
      compensatory homeostatic rise in EAAT2 abundance.

PMID- 20143159
TI  - Serological evidence of bovine herpesvirus-1 (BoHV-1) infection in yaks
      (Peophagus grunniens) from the National Research Centre on Yak, India.
AB  - Bovine herpesvirus-1 (BoHV-1) causes a variety of disease syndromes including,
      respiratory, nervous and reproductive disorders both in domestic as well as wild
      bovines and the disease is prevalent throughout the world including India. In
      this study, serum samples of yaks were screened for serological evidence of BoHV
      1 in a yak farm with history of abortion and kerato-conjuctivitis by competition
      ELISA. The result of seroprevalence of BoHV-1 infections in yaks (Poephagus
      grunniens) revealed that the overall seroprevalence was 60.1%. The sero
      prevalence of BoHV-1 infections was highest in male calf (67.7%) followed by yak
      cows (62.6%), yak bulls (56.8%), and yak heifers (50.0%).

PMID- 20143161
TI  - Inorganic sulfur oxidizing system in green sulfur bacteria.
AB  - Green sulfur bacteria use various reduced sulfur compounds such as sulfide,
      elemental sulfur, and thiosulfate as electron donors for photoautotrophic growth.
      This article briefly summarizes what is known about the inorganic sulfur
      oxidizing systems of these bacteria with emphasis on the biochemical aspects.
      Enzymes that oxidize sulfide in green sulfur bacteria are membrane-bound sulfide
      quinone oxidoreductase, periplasmic (sometimes membrane-bound) flavocytochrome c
      sulfide dehydrogenase, and monomeric flavocytochrome c (SoxF). Some green sulfur
      bacteria oxidize thiosulfate by the multienzyme system called either the TOMES
      (thiosulfate oxidizing multi-enzyme system) or Sox (sulfur oxidizing system)
      composed of the three periplasmic proteins: SoxB, SoxYZ, and SoxAXK with a
      soluble small molecule cytochrome c as the electron acceptor. The oxidation of
      sulfide and thiosulfate by these enzymes in vitro is assumed to yield two
      electrons and result in the transfer of a sulfur atom to persulfides, which are
      subsequently transformed to elemental sulfur. The elemental sulfur is temporarily
      stored in the form of globules attached to the extracellular surface of the outer
      membranes. The oxidation pathway of elemental sulfur to sulfate is currently
      unclear, although the participation of several proteins including those of the
      dissimilatory sulfite reductase system etc. is suggested from comparative genomic
      analyses.

PMID- 20143162
TI  - Community-based participatory research and community health development.

PMID- 20143165
TI  - Monitoring pharmacological therapy for osteoporosis.
AB  - Osteoporosis is a common disease characterized by low bone strength that
      increases the risk of fractures. The consequences of fractures include increases
      in morbidity, mortality, and healthcare costs. Randomized clinical trials have
      shown that pharmacological therapy can reduce the risk of fractures. In clinical
      practice, however, failure to achieve optimal therapeutic benefit is common for
      reasons that include taking medication incorrectly, stopping it prematurely,
      malabsorption, and the presence of unrecognized diseases or conditions with
      adverse skeletal effects. Monitoring for anti-fracture effectiveness in
      individual patients is limited by the absence of clinical tools to directly
      measure bone strength. It is therefore necessary to monitor therapy with
      biomarkers such as bone mineral density and bone turnover markers. This is a
      review of the utility of these tools in the care of individual patients.

PMID- 20143168
TI  - The launch of the Asian Academy of Dental Sleep Medicine.

PMID- 20143166
TI  - Relevance of Helicobacter pylori genotypes in gastric pathology and its
      association with plasma malondialdehyde and nitric oxide levels.
AB  - Persistent infection with Helicobacter pylori confers an increased risk of peptic
      ulceration and gastric adenocarcinoma. Reactive oxygen and nitrogen species play
      a crucial role in the progression from normal gastric mucosa to cancer. The aim
      of the present study was to investigate the plasma malondialdehyde and nitric
      oxide levels in H. pylori related gastroduodenal diseases and associate their
      levels with gastric pathology and genotypes of H. pylori. Malondialdehyde and
      nitric oxide levels in plasma samples of 250 subjects were spectrophotometrically
      determined. Subsequently, genotypic and histopathological assessment was
      performed in gastric biopsies obtained during endoscopy. The levels of MDA and NO
      exceeded in subjects infected with genotype-1 of Hp than those with other
      genotypes suggesting more precise interaction of highly virulent strains of Hp in
      eliciting severe tissue damage. In conclusion, the study demonstrates close
      relationship between the plasma malondialdehyde and nitric oxide levels, gastric
      histopathology and genotypes of H. pylori.

PMID- 20143169
TI  - Photocatalytic degradation of dichlorvos in aqueous TiO2 suspensions.
AB  - INTRODUCTION: In the present work, we explored the kinetics of dichlorvos (2,2
      dichlorvinyl dimethyl phosphate, DDVP) decay through UV-A light-induced TiO(2)
      photocatalysis at pH 4 and 9, and the formation of degradation intermediates and
      final products under specific experimental conditions. Experimental observations
      and theoretical considerations allowed us to suggest the degradation mechanism of
      DDVP by the UV/TiO(2) process in aqueous solution. METHODS: The irradiation
      experiments were carried out in a photoreactor using a 228-W medium-pressure Hg
      vapor lamp. The concentration of DDVP, phosphate ion and formaldehyde as reaction
      intermediate, are determined spectrophotometrically. Chloride ion concentration
      was measured potentiometrically. RESULTS: The photocatalytic degradation rate of
      dichlorvos (DDVP) under UV irradiation (360-380 nm) was optimized with respect to
      the flow rate of O(2) gas sparged into the solution and photocatalyst
      concentration for a constant dichlorvos concentration (1.66 x 10(-4) M) at pH 4.
      Kinetic data were obtained at pH 4 and pH 9 for dichlorvos and the inorganic
      species released through its photo-induced degradation. The proposed mechanism
      which assumes the formation of some toxic intermediates resistant to
      mineralization is supported by theoretical calculations and the observed
      inorganic mass balances. CONCLUSIONS: The calculated pseudo-first-order rate
      constants were dependent on the dissolved oxygen level at low O(2) flow rate, but
      somewhat independent on the initial pH. The decrease of pH during the irradiation
      suggests the formation of organic acids. The presence of organic intermediates
      was confirmed also by TOC measurements. A plausible reaction mechanism of DDVP
      degradation through the UV-A/TiO(2) process was proposed.

PMID- 20143170
TI  - P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative
      diseases.
AB  - A recent study suggested that neuroinflammation plays a major role in the
      pathogenesis of a number of neurodegenerative diseases such as Alzheimer's
      disease and Parkinson's disease. Although the precise mechanism is obscure,
      dysregulation of the signaling transduction pathway in microglia may enhance
      inflammation, leading to synaptic dysfunction and ultimately to neuronal cell
      death. The expression and function of the P2X7 receptor (P2X7R), an ATP-gated ion
      channel abundantly expressed in microglia in the brain, is significantly up
      regulated in the postmortem brain of Alzheimer's disease patients and various
      neurodegenerative disease animal models. This supports the role of the P2X7R
      pathway in the progression of neurodegeneration. Blocking P2X7R using brilliant
      blue G, a P2X7R antagonist that can cross the blood-brain barrier, has been shown
      to result in the amelioration of neuropathology in various animal models. Taken
      together, these results raise the possibility that the P2X7R signaling pathway
      could be a therapeutic target for treating various neurodegenerative diseases.

PMID- 20143171
TI  - The role of thymic stromal lymphopoietin in allergic inflammation and chronic
      obstructive pulmonary disease.
AB  - Thymic stromal lymphopoietin (TSLP) primes dendritic cells to promote a Th2
      inflammatory response. Its action is mediated by a heterodimeric receptor which
      consists of the interleukin-7 receptor alpha chain and the TSLP receptor chain
      (TSLPR). TSLPR resembles the common gamma chain subunit utilized by many type 1
      cytokine receptors. Normal epithelial cells, keratinocytes, and stromal cells
      constitutively express TSLP. Dendritic cells that are activated by TSLP promote
      the development of CD4(+) T cells into pro-inflammatory Th2 cells. TSLP thus
      plays a potentially important role in the pathogenesis of allergic inflammation
      in asthma and atopic dermatitis. TSLP also has direct effects on other types of
      cells in the bronchial mucosa. It is over-expressed in the bronchial mucosa in
      chronic obstructive pulmonary disease (COPD), which is traditionally described as
      a Th1-related disease, as well as severe asthma, which is traditionally described
      as a Th2-related disease. In this review we will discuss TSLP expression,
      function, and available and potential mechanisms in both allergic inflammation
      and COPD.

PMID- 20143173
TI  - Discrimination of left and right leg motor imagery for brain-computer interfaces.
AB  - This article reports on a study to identify electroencephalography (EEG) signals
      with potential to provide new BCI channels through mental motor imagery (MMI).
      Leg motion was assessed to see if left and right leg MMI could be discriminated
      in the EEG. The study also explored simultaneous observation of leg movement as a
      means to enhance MMI evoked EEG signals. The results demonstrate that MMI of the
      left and right leg produce a contralateral preponderance of EEG alpha band
      desynchronization, which can be spatially discriminated. This suggests that lower
      extremity MMI could provide signals for additional BCI channels. The study also
      shows that movement imitation enhances alpha band desynchronization during MMI,
      and might provide a useful aid in the identification and training of BCI signals.

PMID- 20143172
TI  - Lentiviral vectors in gene therapy: their current status and future potential.
AB  - The concept of gene therapy originated in the mid twentieth century and was
      perceived as a revolutionary technology with the promise to cure almost any
      disease of which the molecular basis was understood. Since then, several gene
      vectors have been developed and the feasibility of gene therapy has been shown in
      many animal models of human disease. However, clinical efficacy could not be
      demonstrated until the beginning of the new century in a small-scale clinical
      trial curing an otherwise fatal immunodeficiency disorder in children. This first
      success, achieved after retroviral therapy, was later overshadowed by the
      occurrence of vector-related leukemia in a significant number of the treated
      children, demonstrating that the future success of gene therapy depends on our
      understanding of vector biology. This has led to the development of later
      generation vectors with improved efficiency, specificity, and safety. Amongst
      these are HIV-1 lentivirus-based vectors (lentivectors), which are being
      increasingly used in basic and applied research. Human gene therapy clinical
      trials are currently underway using lentivectors in a wide range of human
      diseases. The intention of this review is to describe the main scientific steps
      leading to the engineering of HIV-1 lentiviral vectors and place them in the
      context of current human gene therapy.

PMID- 20143174
TI  - Advances in the "omics" for diagnosis, pathogenesis, and therapeutic development.

PMID- 20143175
TI  - Trans fatty acid-induced NF-kappaB activation does not induce insulin resistance
      in cultured murine skeletal muscle cells.
AB  - Long-chain saturated fatty acids such as palmitic acid induce insulin resistance
      and NF-kappaB activation in skeletal muscle cells. Here we investigated the
      effects of long-chain fatty acid (FA) saturation and configuration on NF-kappaB
      activity and insulin sensitivity in cultured skeletal muscle cells. Of all tested
      unsaturated FAs, only elaidic acid (3-fold), cis9,trans11-CLA (3-fold) and
      trans10,cis12-CLA (13-fold) increased NF-kappaB transactivation in myotubes. This
      was not accompanied by decreased insulin sensitivity (measured as insulin-induced
      glucose uptake and GLUT4 translocation). We therefore conclude that FA-induced NF
      kappaB activation is not sufficient for the induction of insulin resistance in
      skeletal muscle cells.

PMID- 20143176
TI  - Defensive medicine, cost containment, and reform.
AB  - The role of defensive medicine in driving up health care costs is hotly
      contended. Physicians and health policy experts in particular tend to have
      sharply divergent views on the subject. Physicians argue that defensive medicine
      is a significant driver of health care cost inflation. Policy analysts, on the
      other hand, observe that malpractice reform, by itself, will probably not do much
      to reduce costs. We argue that both answers are incomplete. Ultimately,
      malpractice reform is a necessary but insufficient component of medical cost
      containment. The evidence suggests that defensive medicine accounts for a small
      but non-negligible fraction of health care costs. Yet the traditional medical
      malpractice reforms that many physicians desire will not assuage the various
      pressures that lead providers to overprescribe and overtreat. These reforms may,
      nevertheless, be necessary to persuade physicians to accept necessary changes in
      their practice patterns as part of the larger changes to the health care payment
      and delivery systems that cost containment requires.

PMID- 20143177
TI  - Health risks, chronic diseases, and access to care among US Pacific Islanders.
AB  - BACKGROUND: Because Pacific Islanders and Asian Americans have often been
      aggregated in federal health surveys, we assessed whether they differ
      substantially in important health measures. DESIGN: Retrospective analyses of the
      2005-2007 Behavioral Risk Factor Surveillance System (BRFSS) surveys.
      PARTICIPANTS: A total of 2,609 Pacific Islanders, 17,892 Asians, and 894,289
      whites over age 18. MEASUREMENTS: We compared self-reported health risk factors
      (smoking, BMI > or = 25 kg/m(2), alcohol intake, physical activity,
      fruit/vegetable intake), chronic diseases (diabetes, hypertension, coronary heart
      disease, asthma, hypercholesterolemia, arthritis, fair or poor health status),
      and access to care (insurance status, cost barriers, and regular physician) for
      Pacific Islanders relative to Asian Americans and whites. Logistic regression was
      used to adjust for sociodemographic factors. RESULTS: Pacific Islanders were more
      likely than Asian Americans to report an elevated body-mass index (adjusted odds
      ratio 2.26; 95% confidence interval 1.80, 2.84), current smoking (2.15; 1.57,
      2.93), and high alcohol intake (3.14; 1.60, 6.18), but also more likely to report
      adequate physical activity (1.62; 1.23, 2.14). Pacific Islanders reported higher
      adjusted rates of hypertension (1.50; 1.06, 2.13), diabetes (1.82; 1.25, 2.63),
      asthma (2.32; 1.65, 3.25), and arthritis (1.68; 1.20, 2.35). Pacific Islanders
      also more frequently reported having fair or poor health (1.46; 1.05, 2.04). Most
      differences in self-reported health status and chronic disease outcomes were
      mediated by higher rates of overweight and obesity, but not higher rates of
      smoking, among Pacific Islanders. Differences in smoking, hypertension, and
      diabetes were more pronounced among Pacific Islander women than men. Relative to
      whites, Pacific Islanders were more likely to report a diagnosis of diabetes
      (1.56; 1.13, 2.14) and less likely to report arthritis (0.61; 0.46, 0.82). All
      other outcomes measures were statistically similar for whites and Pacific
      Islanders. CONCLUSION: Health surveys and policies should distinguish between
      Pacific Islanders and Asian Americans given the significantly higher rates of
      health risks and chronic diseases among Pacific Islanders.

PMID- 20143179
TI  - Internal hernias and nonclosure of mesenteric defects during laparoscopic Roux-en
      Y gastric bypass.

PMID- 20143180
TI  - Outcomes, satiety, and adverse upper gastrointestinal symptoms following
      laparoscopic adjustable gastric banding.
AB  - BACKGROUND: Follow-up is critical to the success of laparoscopic adjustable
      gastric banding (LAGB). Few data guide this and expected norms of satiety,
      adverse symptoms, and outcomes have not been defined. METHODS: Consecutive
      patients, who underwent LAGB, were evaluated using a newly developed instrument
      that assessed satiety, adverse upper gastrointestinal (dysphagia, reflux, and
      epigastric pain), and outcomes (overall satisfaction, weight loss, and quality of
      life (SF-36)). RESULTS: Three hundred twenty-three of 408 patients responded
      (80%; mean age 44.4 +/- 11.8 years, 56 males). Excess weight loss was 52%.
      Satiety was greater at breakfast compared to lunch (5.3 +/- 1.9 vs. 4.1 +/- 1.7,
      p < 0.005) or dinner (3.8 +/- 1.8, p < 0.005). The satisfaction score was 8.3 +/-
      2.1 out of 10, and 91% would have the surgery again. Quality of life was less
      than community norms, except in physical functioning (83.4 +/- 20.5 vs. 84.7 +/-
      22.0, p = 0.25) and bodily pain (78.4 +/- 15.2 vs. 75.9 +/- 25.3, p = 0.004).
      Inability to consume certain foods was cited as the biggest problem by 66% of
      respondents. The dysphagia score was 19.9 +/- 8.7; softer foods were tolerated,
      although difficulty was noted with firmer foods. The reflux score was 8.7 +/- 9.8
      and regurgitation occurred a mean of once per week. Weight loss and the mental
      component score were the only predictors of overall satisfaction (r2 = 0.46, p =
      0.01). CONCLUSIONS: Patients are highly satisfied with the outcome of LAGB and
      achieve substantial weight after 3 years. Expected ranges of satiety, adverse
      symptoms, and outcomes have been defined. The most troublesome symptom is the
      inability to consume certain foods. Weight loss predicted overall satisfaction,
      regardless of adverse symptoms.

PMID- 20143181
TI  - Interaction of zinc, ascorbic acid, and folic acid in glycation with albumin as
      protein model.
AB  - Using albumin as model, we conducted series of in vitro glycation experiments to
      examine role of zinc in glycation using glucose at 4-100 mg/ml, incubations at 37
      degrees C or 60 degrees C, duration of 2 or 4 weeks and in presence of zinc or
      ascorbic acid (AA) or folic acid (FA). Modifications of bovine serum albumin
      (BSA) were examined by using fluorescence of advanced glycation end products
      (AGEs) and dityrosine, UV, and Fourier transformed infrared spectroscopy. Adding
      zinc (0 to 768.5 MUmol/l) resulted in significant inhibition of albumin glycation
      by glucose with a linear fit, y = -0.0895x + 230.99(R2 = 0.7676, p = 0.013). The
      glycation by fructose was greater than that of glucose with stronger inhibitory
      effect by zinc in fructose-glycation (t= -5.8, p=0.002). Addition of zinc
      significantly decreased fluorescence as seen in Zn + FA or Zn + AA sets as
      compared to sets of FA alone (p=0.00056) or AA alone (p=0.037). The fluorescence
      for dityrosine and AGE had a correlation of 0.897 (p<0.01). The data from
      fluorescence, UV, and FTIR spectra collectively suggested inhibitory effect of
      zinc in BSA glycation alone or in presence of FA and AA, showing new dimension
      for the protective action of zinc in hyperglycemic conditions.

PMID- 20143182
TI  - Diagnosis and classification of systemic sclerosis.
AB  - As the diagnosis of systemic sclerosis (SSc) is generally suggested by the
      presence of Raynaud's phenomenon followed by typical skin thickening associated
      with the presence of additional extracutaneous features, capillaroscopic
      abnormalities, and characteristic autoantibodies, the first classification
      criteria, published by the American Rheumatism Association in 1980, were based
      only on clinical and chest X-ray items. As a consequence, 10% to 20% of the
      patients did not meet these criteria. In 1988, an international consensus was
      reached resulting in the proposal of a new and more practical classification
      based on the judgment and clinical practice of an expert panel. This
      classification introduced the SSc nail fold capillaroscopy abnormalities
      (dilation and/or avascular areas) and specific antinuclear antibodies. Two
      subsets of SSc emerged from discussions: diffuse cutaneous SSc (dcSSc) and
      limited cutaneous SSc (lcSSc). The calcifications, Raynaud's phenomenon,
      esophageal hypomotility, sclerodactyly, and telangiectasia (CREST) syndrome can
      be considered an lcSSc. In 2001, LeRoy and Medsger, realizing the shortcomings of
      the 1988 subsets in being too exclusive and taking advantage of increased
      experience with nail fold capillaroscopy and autoantibody determination, proposed
      criteria for an additional early or limited subset of SSc (lSSc), to supplement
      the previously recognized lcSSc and dcSSc forms. Patients with lSSc must have
      Raynaud's phenomenon and SSc-specific nail fold capillary changes and/or SSc
      specific autoantibodies. Some lSSc patients who have no cutaneous involvement but
      common SSc nail fold capillaroscopy abnormalities, specific antinuclear
      antibodies, and visceral involvement are sometimes called SSc sine scleroderma.
      Whether or not lSSc and SSc sine scleroderma are the same or two different
      subsets is currently not known.

PMID- 20143183
TI  - Production of a soluble disulfide bond-linked TCR in the cytoplasm of Escherichia
      coli trxB gor mutants.
AB  - Previously, we have described the use of phage display to generate high affinity
      disulfide bond-linked T cell receptors (TCRs). The affinities of the mutant TCRs
      were analysed after refolding of separately expressed alpha and beta chains from
      Escherichia coli inclusion bodies. This approach is only suitable for the
      analysis of small numbers of TCR variants. An attractive alternative would be
      soluble expression within the bacterial periplasm, but the generic production of
      TCRs within the E. coli periplasm has so far not proved successful. Here we show
      that functional, soluble TCR can be produced within the cytoplasm of trxB gor
      mutant E. coli strains, with maximum yields of 3.4 mg/l. We also investigated the
      effect of coexpressing the folding modulators Skp and DsbC finding that the TCR
      expression levels were largely unaffected by these chaperones. Importantly, we
      demonstrated that the amount of protein purified from 50 ml starter cultures was
      sufficient to show functionality of the TCR by specific antigen binding in both
      ELISA and surface plasmon resonance (SPR) assays. This TCR production method has
      the potential to allow rapid and medium throughput analysis of affinity-matured
      TCRs selected from TCR phage display libraries.

PMID- 20143184
TI  - Recombinant baculovirus as a highly potent vector for gene therapy of human
      colorectal carcinoma: molecular cloning, expression, and in vitro
      characterization.
AB  - Present therapeutic strategies for most cancers are restricted mainly to the
      primary tumors and are also not very effective in controlling metastatic states.
      Alternatively, gene therapy can be a potential option for treating such cancers.
      Currently mammalian viral-based cancer gene therapy is the most popular approach,
      but the efficacy has been shown to be quite low in clinical trials. In this
      study, for the first time, the insect cell-specific baculovirus Autographa
      californica multiple nucleopolyhedrovirus (AcMNPV) has been evaluated as a vector
      for gene delivery to colorectal cancer cells. Experiments involving factorial
      design were employed to study the individual and combined effects of different
      parameters such as multiplicity of infection (MOI), viral incubation time and
      epigenetic factors on transduction efficiency. The results demonstrate that
      baculovirus gene delivery system holds immense potential for development of a new
      generation of highly effective virotherapy for colorectal, as well as other major
      carcinomas (breast, pancreas, and brain), and offers significant benefits to
      traditional animal virus-based vectors with respect to safety concerns.

PMID- 20143185
TI  - Predictive value of ERCC1 and XPD polymorphism in patients with advanced non
      small cell lung cancer receiving platinum-based chemotherapy: a systematic review
      and meta-analysis.
AB  - The published data on the predictive value of polymorphism of ERCC1 and XPD in
      patients with advanced non-small cell lung cancer receiving platinum-based
      chemotherapy are inconclusive. To derive a more precise estimation of the
      relationship, a meta-analysis was performed. Relevant studies were identified by
      searching the Medline, Embase, CNKI and American Society of Clinical Oncology
      abstract databases. Inclusion criteria were patients with advanced NSCLC,
      received platinum-based chemotherapy, evaluation of polymorphism of ERCC1 and XPD
      and overall response rate (ORR). A total of 12 studies were included in this meta
      analysis. For studies evaluating ERCC1 polymorphism at codon 118, the ORR for the
      wild-type C/C genotype versus the heterozygous C/T and T/T genotype was 2.17 (95%
      confidence interval (CI), 1.43-3.33; P = 0.000). For studies evaluating XPD
      Asp312Asn and XPD Lys751Gln, the pooled OR was 1.33 (95% CI, 0.92-1.91; P = 0.13)
      and 1.02 (95% CI, 0.72-1.45; P = 0.915), respectively. The results indicated that
      platinum-based chemotherapy sensitivity was significantly associated with
      polymorphism of ERCC1 C118T. However, XPD Asp312Asn and XPD Lys751Gln were not
      predictive makers for platinum-based chemotherapy in patients with advanced
      NSCLC.

PMID- 20143186
TI  - Concomitant Hodgkin's lymphoma and gastric adenocarcinoma: a rare coincidence.
AB  - Gastric adenocarcinomas may be seen together with colon, prostate, breast, liver,
      lung and gynecological malignancies as synchronous or metachronous cancer.
      However, Hodgkin's lymphoma (HL) is rarely diagnosed with solid tumors. Herein, a
      72-year-old man with both gastric adenocarcinoma and HL has been presented. Mass
      lesions far away from the primary tumor in cancer patients can be not only the
      sign of distant metastasis but also another primary malignancy. In the English
      literature, synchronous gastric adenocarcinoma and HL has been rarely reported,
      and as far as we know, this is the third case to be reported.

PMID- 20143187
TI  - Prognostic value of beta-catenin, c-myc, and cyclin D1 expressions in patients
      with esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most frequently diagnosed
      malignant tumors in North China. We have identified that Wnt2/beta-catenin
      pathway is activated in ESCC cells and sodium nitroprusside (SNP) and siRNA
      against beta-catenin not only inhibit the expressions of beta-catenin and its
      major downstream effectors including c-myc and cyclin D1 but induce cell cycle
      arrest and apoptosis. The purpose of the present study was to analyze the
      relationship between pathological parameters including invasion depth and lymph
      node metastasis and the expressions of beta-catenin, c-myc, and cyclin D1 in
      order to evaluate their values of prognosis in patients with ESCC. The
      expressions of beta-catenin, c-myc, and cyclin D1 were detected
      immunohistochemically in the resected cancer tissues from 40 patients with ESCC.
      The beta-catenin expression was reduced in 22 (55.0%) patients, which was closely
      correlated with invasion depth (P = 0.023) and lymph node metastasis (P = 0.003).
      There was the positive c-myc expression in 21 (52.5%), which was significantly
      correlated with invasion depth (P = 0.009) and lymph node metastasis (P = 0.001).
      Furthermore, the results of survival rates analyzed by Kaplan-Meier curve
      revealed that patients with the reduced expression of beta-catenin had a poorer
      prognosis than those with the preserved expression (P = 0.031), and patients with
      the positive expression of c-myc also had a significantly poorer prognosis than
      those with the negative expression (P = 0.008). These findings demonstrate that
      beta-catenin pathway plays a crucial role in the progression of ESCC, suggesting
      that both beta-catenin and c-myc may be used as markers for predicting the
      prognosis of patients with ESCC.

PMID- 20143189
TI  - Breast density, scintimammographic (99m)Tc(V)DMSA uptake, and calcitonin gene
      related peptide (CGRP) expression in mixed invasive ductal associated with
      extensive in situ ductal carcinoma (IDC + DCIS) and pure invasive ductal
      carcinoma (IDC): correlation with estrogen receptor (ER) status, proliferation
      index Ki-67, and histological grade.
AB  - BACKGROUND: We evaluated the variation of calcitonin gene related peptide (CGRP)
      expression in patients with mixed invasive with extensive in situ ductal
      carcinomas (IDC + DCIS) and pure IDC, in relation to mammographic breast density
      (%BD), proliferation-seeking radiotracer (99m)Tc(V) dimercaptosuccinic acid
      (DMSA) uptake (scintimammographic-SMM), proliferation index Ki-67, and estrogen
      receptor (ER) status. We also assessed CGRP expression with histological grade.
      METHODS: We studied retrospectively 24 women with suspicious findings on
      mammography who were evaluated preoperatively with (99m)Tc(V)DMSA
      scintimammography. Histology revealed 12 IDC (grade II in 8, grade III in 4
      patients; mean size +/- SD, 2.6 +/- 1.3 cm; mean age +/- SD, 66.5 +/- 13.1 years)
      and 12 IDC + DCIS (grade II in 6, grade III in 6 patients; DCIS component mean
      size +/- SD, 5.3 +/- 1.8 cm; IDC component mean size +/- SD, 2.5 +/- 1.1 cm; mean
      age +/- SD, 58.5 +/- 15.1 years). Immunohistochemistry for CGRP, Ki-67, and ER
      status was performed in all 24 surgical specimens. BD and SMM were calculated by
      computer-assisted methods and were statistically correlated with CGRP expression.
      BD, SMM, Ki-67, and ER were statistically compared between IDC and IDC + DCIS,
      whereas CGRP, Ki-67, and ER were compared between patients with BD >25 and <25%.
      CGRP was also compared (t test) between grade II and grade III in both groups.
      RESULTS: Overall positive correlation was found between BD and CGRP (r = 0.577, P
      < 0.001). Positive correlation was established between SMM and CGRP only in IDC +
      DCIS (r (SMM(IDC+DCIS)-CGRP) = 0.634, P < 0.05). CGRP and Ki-67 were
      significantly higher in patients with BD >25% compared with <25% BD patients (P =
      0.00008 and P = 0.014, respectively). BD and SMM were significantly higher in
      CGRP(+) than in CGRP(-) patients as well as in IDC + DCIS compared with IDC. Ki
      67 was significantly higher, whereas ER was significantly lower, in IDC + DCIS
      than in IDC. In all patients, CGRP was significantly higher in grade II as
      compared with grade III (P = 0.005). In the mixed group (IDC + DCIS), grade II
      cancers had also significantly higher CGRP values as compared with grade III ones
      (P = 0.004). In pure IDC, no statistical difference was found between grade II
      and III (P = 0.4). CONCLUSIONS: BetaD, SMM, CGRP, and Ki-67 were significantly
      increased, whereas ER was significantly decreased, in IDC + DCIS as compared with
      IDC, indicating that IDC + DCIS is an entity that is more aggressive, ER
      independent, and possibly associated with a pathway linked to stromal involvement
      and CGRP activity.

PMID- 20143188
TI  - miRNA-21 regulates arsenic-induced anti-leukemia activity in myelogenous cell
      lines.
AB  - MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules involved in
      modulation of cellular sensitivity to anti-cancer drugs. miRNA-21 (miR-21), one
      of the most prominent miRNAs in the genesis and progression of many human
      cancers, has been rarely characterized in myelogenous leukemia. Arsenic trioxide
      (ATO) was successfully used in the treatment of acute promyelocytic leukemia
      (APL) etc. However, cytotoxicity or insensitivity is a major concern in the
      successful treatment of leukemia. Here, we used a specific precursor miRNA-21
      (pre-miR-21) or anti-miRNA-21 oligonucleotide (AMO-miR-21) to study sensitivity
      of HL60 and K562 cells to ATO. Cell viability and cell cycle were evaluated by
      MTT assay and PI assay using flow cytometry, respectively. Levels of miR-21 and
      its target PDCD4 were quantified by real-time PCR and/or western blot. AMO-miR-21
      or ATO alone led to growth inhibition, apoptosis and G1 phase arrest of cell
      cycle. Apoptotic cells were confirmed morphologically with Hoechst staining.
      Moreover, there was somewhat synergistic effect of AMO-miR-21 and ATO in growth
      inhibition and apoptosis promotion. Meanwhile, enforced pre-miR-21 expression
      increased resistance to ATO, nevertheless not affecting cell growth alone. Dual
      luciferase reporter vector containing two tandem PDCD4 3' UTR validated that
      PDCD4 was directly up-regulated by miR-21. Therefore, miRNA-21 by targeting PDCD4
      may play a functional role in modulating ATO-induced cell death, and strategy
      using AMO-miR-21 and its combination with ATO may be useful as a myelogenous
      leukemia therapy.

PMID- 20143190
TI  - Current status and issues of screening digital mammography in Japan.
AB  - Digital systems have replaced screen-film systems, and have already been used for
      a screening program. The diagnostic performance of digital systems has been
      compared with that of screen-film systems, as the golden standard of breast
      cancer screening. Several studies have demonstrated they are superior to screen
      film mammography; others have shown performance is comparable. The validity of
      digital screening mammography has been demonstrated. Regarding the method of
      interpretation of digital screening mammograms, the performance of hard-copy and
      soft-copy reading has been reported to be comparable, although the environment of
      soft-copy reading was premature. Soft-copy reading seems more promising in the
      future as a result of the development of both hardware and software. However,
      many aspects of quality assurance of soft-copy reading (e.g. standard
      specifications of viewing workstation, contrast visibility and resolution,
      ambient light) which remain undetermined should be clarified in the Japanese
      guideline. In Japan the average glandular dose in screening digital mammography
      is higher than that in screen-film mammography. Most (93.2%) are under 2 mGy for
      each radiation exposure. The risk of breast cancer by radiation exposure is
      regarded as higher than before in the 2007 recommendations of the ICRP.
      Management of radiation exposure is a continuing challenge.

PMID- 20143191
TI  - Fresh osteochondral allografting for steroid-associated osteonecrosis of the
      femoral condyles.
AB  - BACKGROUND: Osteonecrosis is a complication of corticosteroid therapy with
      limited treatment options in young, active patients. These options include
      debridement, core decompression, osteotomy, allografting, and partial or total
      knee replacement. Few studies exist regarding the use of osteochondral allografts
      for treatment of steroid-associated osteonecrosis. QUESTIONS/PURPOSES: We asked
      if fresh osteochondral allografts would (1) heal to host bone in the presence of
      osteonecrosis, (2) provide a clinically meaningful decrease in pain and
      improvement in function, and (3) prevent or postpone the need for prosthetic
      arthroplasty. PATIENTS AND METHODS: Twenty-two patients (28 knees) who underwent
      osteochondral allografting for high-grade, corticosteroid-associated
      osteonecrosis were evaluated. Their average age was 24.3 years (range, 16-44
      years). The mean graft surface area was 10.8 cm(2) (range, 5.0-19.0 cm(2)).
      Evaluation included a modified (for the knee) D'Aubigne and Postel (18-point)
      score, International Knee Documentation Committee (IKDC), and Knee Society
      function scores. The minimum followup was 25 months (mean, 67 months; range, 25
      235 months). RESULTS: Five knees failed. The graft survival rate was 89% (25 of
      28). The mean D'Aubigne and Postel score improved from 11.3 to 15.8; 19 of 25
      (76%) had a score greater than 15. The mean IKDC pain score improved from 7.1 to
      2.0, mean IKDC function score from 3.5 to 8.3, and mean Knee Society function
      score from 60.0 to 85.7. CONCLUSIONS: Our data suggest osteochondral allografting
      is a reasonable salvage option for osteonecrosis of the femoral condyles. TKA was
      avoided in 27 of the 28 of knees at last followup. LEVEL OF EVIDENCE: Level IV,
      case series. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 20143192
TI  - On a fatal case of Candida krusei pleural empyema in a pregnant woman with
      spontaneous esophagus perforation.
AB  - INTRODUCTION: Candida empyema thoracis can be a consequence of operation,
      gastropleural fistula, and esophageal perforation. Case report and review of the
      literature. A fatal case of a 45-year-old pregnant woman with Candida krusei
      empyema thoracis secondary to spontaneous esophagus perforation associated with
      candida esophagitis is reported. The case is contextualized among similar cases
      found through a PubMed search. CONCLUSIONS: A suspect of esophagus rupture should
      arise in the presence of a fungal empyema. Candida esophagitis should be always
      considered as a possible cause or con-cause of esophagus rupture. An empirical
      systemic antimycotic therapy should always be considered in an ideal
      multidisciplinary approach to the management of patients with esophagus rupture.

PMID- 20143193
TI  - Determining Candida spp. incidence in denture wearers.
AB  - The aim of this study was to determine Candida spp. incidence in the oral cavity
      of denture wearers and characterize predisposing factors in denture-related
      stomatitis (DRS). Three groups of denture wearers and a control group were
      evaluated for DRS according to Newton's classification. The amount of yeast in
      saliva and the presence of yeast on mucosal surfaces were determined by
      phenotyping methods, and the impact of some risk factors on candidal carriage was
      evaluated. The development of DRS is most common in complete prosthesis users.
      When the count of yeast in saliva is >or=400 cfu/ml, the frequency of DRS is
      increased. In individuals who develop DRS, the most frequently encountered
      species that was identified as C. albicans. Prosthetic hygiene was related to the
      intensity of candidal growth and the development of DRS. C. albicans live as
      saprophyte in the oral cavity. But, it is capable of causing infection if there
      are predisposing conditions related to the host. Usage of removable prosthesis
      may cause these microorganisms to gain pathogenicity.

PMID- 20143194
TI  - Biomaterials/tissue interactions: possible solutions to overcome foreign body
      response.
AB  - In recent years, a variety of biomaterial implantable devices has been developed.
      Of particular significance to pharmaceutical sciences is the progress made on the
      development of drug/implantable device combination products. However, the
      clinical application of these devices is still a critical issue due to the host
      response, which results from both the tissue trauma during implantation and the
      presence of the device in the body. Accordingly, the in vivo functionality and
      durability of any implantable device can be compromised by the body response to
      the foreign material. Numerous strategies to overcome negative body reactions
      have been reported. The aim of this review is to outline some key issues of
      biomaterial/tissue interactions such as foreign body response and
      biocompatibility and biocompatibility assessment. In addition, general approaches
      used to overcome the in vivo instability of implantable devices are presented,
      including (a) biocompatible material coatings, (b) steroidal and nonsteroidal
      anti-inflammatory drugs, and (c) angiogenic drugs. In particular, strategies to
      overcome host response to glucose biosensors are summarized.

PMID- 20143195
TI  - Augmentation of therapeutic efficacy in drug-resistant tumor models using
      ceramide coadministration in temporal-controlled polymer-blend nanoparticle
      delivery systems.
AB  - The development of multidrug resistance (MDR) is a major hindrance to cancer
      eradication as it renders tumors unresponsive to most chemotherapeutic treatments
      and is associated with cancer resurgence. This study describes a novel mechanism
      to overcome MDR through a polymer-blend nanoparticle platform that delivers a
      combination therapy of C6-ceramide (CER), a synthetic analog of an endogenously
      occurring apoptotic modulator, together with the chemotherapeutic drug paclitaxel
      (PTX), in a single formulation. The PTX/CER combination therapy circumvents
      another cellular mechanism whereby MDR develops, by lowering the threshold for
      apoptotic signaling. In vivo studies in a resistant subcutaneous SKOV3 human
      ovarian and in an orthotopic MCF7 human breast adenocarcinoma xenograft showed
      that the PTX and CER nanoparticle combination therapy reduced the final tumor
      volume at least twofold over treatment with the standard PTX therapy alone. The
      study also revealed that the cotherapy accomplished this enhanced efficacy by
      generating an enhancement in apoptotic signaling in both tumor types.
      Additionally, acute evaluation of safety with the combination therapy did not
      show significant changes in body weight, white blood cell counts, or liver enzyme
      levels. The temporal-controlled nanoparticle delivery system presented in this
      study allows for a simultaneous delivery of PTX + CER in breast and ovarian tumor
      model drug, leading to a modulation of the apoptotic threshold. This strategy has
      tremendous potential for effective treatment of refractory disease in cancer
      patients.

PMID- 20143196
TI  - Liposomal simvastatin attenuates neointimal hyperplasia in rats.
AB  - Monocytes, macrophages, and inflammation play a key role in the process of
      neointimal proliferation and restenosis. The present study evaluated whether
      systemic and transient depletion of monocytes could be obtained by a single
      intravenous (IV) injection of simvastatin liposomes, for the inhibition of
      neointima formation. Balloon-injured carotid artery rats (n = 30) were randomly
      assigned to treatment groups of free simvastatin, simvastatin in liposomes (3
      mg/kg), and saline (control). Stenosis and neointima to media ratio (N/M) were
      determined 14 days following single IV injection at the time of injury by
      morphometric analysis. Depletion of circulating monocytes was determined by flow
      cytometry analyzes of blood specimens. Inhibition of RAW264.7, J774, and THP-1
      proliferation by simvastatin-loaded liposomes and free simvastatin was determined
      by the 3-(4, 5-dimethylthiazolyl-2)-2, 5- diphenyltetrazolium bromide assay.
      Simvastatin liposomes were successfully formulated and were found to be 1.5-2
      times more potent than the free drug in suppressing the proliferation of
      monocytes/macrophages in cell cultures of RAW 264.7, J774, and THP-1. IV
      injection of liposomal simvastatin to carotid-injured rats (3 mg/kg, n = 4)
      resulted in a transient depletion of circulating monocytes, significantly more
      prolonged than that observed following treatment with free simvastatin.
      Administration to balloon-injured rats suppressed neointimal growth. N/M at 14
      days was 1.56 +/- 0.16 and 0.90 +/- 0.12, control and simvastatin liposomes,
      respectively. One single systemic administration of liposomal simvastatin at the
      time of injury significantly suppresses neointimal formation in the rat model of
      restenosis, mediated via a partial and transient depletion of circulating
      monocytes.

PMID- 20143197
TI  - The cerebellum in children with spina bifida and Chiari II malformation:
      Quantitative volumetrics by region.
AB  - Few volumetric MRI studies of the entire cerebellum have been published; even
      less quantitative information is available in patients with hindbrain
      malformations, including the Chiari II malformation which is ubiquitous in
      patients with spina bifida meningomyelocele (SBM). In the present study, regional
      volumetric analyses of the cerebellum were conducted in children with SBM/Chiari
      II and typically developing (TD) children. Total cerebellar volume was
      significantly reduced in the SBM group relative to the TD group. After correcting
      for total cerebellum volume, and relative to the TD group, the posterior lobe was
      significantly reduced in SBM, the corpus medullare was not different, and the
      anterior lobe was significantly enlarged. Children with thoracic level lesions
      had smaller cerebellar volumes relative to those with lumbar/sacral lesions, who
      had smaller volumes compared to TD children. The reduction in cerebellar volume
      in the group with SBM represents not a change in linear scaling but rather a
      reconfiguration involving anterior lobe enlargement and posterior lobe reduction.

PMID- 20143198
TI  - Environmental enrichment does not reduce the rewarding and neurotoxic effects of
      methamphetamine.
AB  - Abuse of amphetamine analogues, such as methamphetamine (METH), represents an
      important health problem because of their powerful addictive and neurotoxic
      effects. Abuse of METH induces dopamine neuron terminals loss and cell death in
      the striatum similar to what is found in other neurodegenerative processes.
      Exposing mice and rats to enriched environments (EE) has been shown to produce
      significant protective effects against drug-induced reward as well as against
      neurodegenerative processes. Here, we investigated whether exposure to EE could
      reduce the METH-induced reward and neurotoxicity. For this, we reared mice for 2
      months during early stages of life in standard environments or EE and then, at
      adulthood, we tested the ability of METH to induce conditioned place preference
      and neurotoxicity. We found that, contrary to what we found with other drugs such
      as cocaine and heroin, EE was unable to reduce the rewarding effects of METH. In
      addition, contrary to what we found with other toxins such as MPTP, EE did not
      diminish the striatal neurotoxicity induced by METH (4 x 10 mg/kg) as measured by
      dopamine content, tyrosine hydroxylase protein levels and apoptosis. Our results
      demonstrate that the rewarding and neurotoxic effects of METH are not reduced by
      EE and highlight the great risks associated with the increased popularity of this
      drug amongst the young population.

PMID- 20143199
TI  - Dopamine system dysregulation by the ventral subiculum as the common
      pathophysiological basis for schizophrenia psychosis, psychostimulant abuse, and
      stress.
AB  - The dopamine system is under multiple forms of regulation, and in turn provides
      effective modulation of system responses. Dopamine neurons are known to exist in
      several states of activity. The population activity, or the proportion of
      dopamine neurons firing spontaneously, is controlled by the ventral subiculum of
      the hippocampus. In contrast, burst firing, which is proposed to be the
      behaviorally salient output of the dopamine system, is driven by the brainstem
      pedunculopontine tegmentum (PPTg). When an animal is exposed to a behaviorally
      salient stimulus, the PPTg elicits a burst of action potentials in the dopamine
      neurons. However, this bursting only occurs in the portion of the dopamine neuron
      population that is firing spontaneously. This proportion is regulated by the
      ventral subiculum. Therefore, the ventral subiculum provides the gain, or the
      amplification factor, for the behaviorally salient stimulus. The ventral
      subiculum itself is proposed to carry information related to the environmental
      context. Thus, the ventral subiculum will adjust the responsivity of the dopamine
      system based on the needs of the organism and the characteristics of the
      environment. However, this finely tuned system can be disrupted in disease
      states. In schizophrenia, a disruption of interneuronal regulation of the ventral
      subiculum is proposed to lead to an overdrive of the dopamine system, rendering
      the system in a constant hypervigilant state. Moreover, amphetamine sensitization
      and stressors also appear to cause an abnormal dopaminergic drive. Such an
      interaction could underlie the risk factors of drug abuse and stress in the
      precipitation of a psychotic event. On the other hand, this could point to the
      ventral subiculum as an effective site of therapeutic intervention in the
      treatment or even the prevention of schizophrenia.

PMID- 20143201
TI  - [Sponsorship of medical congresses, workshops and symposia by the pharmaceutical
      industry: as a physician, exercise caution!].

PMID- 20143200
TI  - Glycogen synthase kinase 3beta and its phosphorylated form (Y216) in the paraquat
      induced model of parkinsonism.
AB  - Parkinson's disease is a slowly progressing disease, due to a lesion of
      dopaminergic neurons in the substantia nigra and a dramatic loss of dopamine in
      the striatum. It is now accepted that several environmental agents including the
      herbicide paraquat (PQ) may contribute to its pathogenesis. However, till now
      nothing is known about the role of glycogen synthase kinase-3beta (GSK-3beta) in
      the PQ toxicity. Therefore, the aim of this study was to examine the influence of
      37-week administration of PQ in rats on the immunohistochemically measured levels
      of the total GSK-3beta and its active, tyrosine 216 (pY216)-phosphorylated form
      in subcellular fractions of the midbrain with pons, as well as of the striatum.
      The present results revealed that the long-term PQ administration increased the
      levels of total and active forms of GSK-3beta in the midbrain with pons, whereas
      decreased them in the striatum. Examination of the lesion extent showed a
      decrease in the number of tyrosine-immunoreactive neurons in the substantia nigra
      pars compacta, ventral tegmental area, and locus coeruleus, as well as lower
      DOPAC/dopamine ratio and noradrenaline level in the striatum in rats treated with
      PQ. The long-term PQ administration disturbed also motor activity of rats.
      Summarizing, the present data indicate that the long-term exposure of rats to PQ,
      a commonly used herbicide, diversely alters levels of GSK-3beta in different
      brain structures, which may be associated with their vulnerability to its
      toxicity.

PMID- 20143202
TI  - [Humor therapy in the depressed elderly: results of an empirical study].
AB  - BACKGROUND: Positive effects of humor on older patients with depressive symptoms
      have been repeatedly reported. Empirical evidence, however, is rare. We
      investigated the effects of a standardized humor therapy group in a clinical
      context especially for older depressed patients. PATIENTS AND METHODS: For this
      purpose, an experimental group with treatment (52 patients participating in the
      humor group) was compared to a control group with no specific treatment (38
      patients); all 90 participants had clinical depressive symptoms according to ICD
      10 classification. Questionnaires (among them GDS, SF-12, State-Trait
      Cheerfulness Inventory, Satisfaction with Life Scale) were administered at two
      time points (pre- and post-treatment). RESULTS: From pre- to post-measurement,
      significant improvements could be shown only in the experimental group for
      resilience and satisfaction with life (p<0.05). Analyses of the subgroups with at
      least medium to severe depression showed further significant effects for
      cheerfulness, seriousness, bad mood, and satisfaction with life (p<0.05). These
      severely affected patients seemed to profit best from humor therapy. CONCLUSION:
      Our results indicate the efficacy of this specific therapeutic intervention for
      older depressed patients.

PMID- 20143203
TI  - [Highlights of the 5th EUGMS congress, Copenhagen 2008 ].

PMID- 20143205
TI  - [Report from the German Federation of Geriatrics (BV Geriatrie)].

PMID- 20143206
TI  - OM-85 BV, an immunostimulant in pediatric recurrent respiratory tract infections:
      a systematic review.
AB  - BACKGROUND: This study was conducted to assess the efficacy of OM-85 BV (Broncho
      Vaxom) in the prevention of pediatric recurrent respiratory tract infections
      (RTIs). Available evidence suggests that defining recurrent RTIs as >or=3
      infections per fall-winter semester is both medically and epidemiologically
      justified. Therefore, this criterion was chosen as a primary endpoint. METHODS:
      Trials were identified through consultation of bibliographic databases and other
      channels. Eleven non-blinded studies plus one dealing with primary prevention
      were excluded and eight randomized controlled trials were included in the meta
      analysis. The data were compared at 6 months, which represented the end of most
      studies. The complete database was examined according to the guidelines of the
      Cochrane collaboration. RESULTS: The mean age of children and the number of RTIs
      in the preceding year were comparable at admission. Of the patients in the OM-85
      BV treated population (n=435), 32% had recurrent RTIs (that is, >or=3 RTIs/6
      months) vs. 58.2% in the placebo treated population (n=416; P<0.001). Sensitivity
      analysis showed that this was not driven by any particular trial. The results of
      this review were also positive for the active treatment regarding the secondary
      variables, which were represented by the number of patients with at least one RTI
      and the mean number of RTIs. CONCLUSIONS: This meta-analysis shows, as observed
      in several individual trials, that the population treated with OM-85 BV had
      significantly and consistently fewer cases of recurrent RTIs. The data suggest
      that the effect is greater in patients at increased risk of recurrent RTIs.

PMID- 20143208
TI  - Vaginal microbiocoenosis and cytology of prepubertal and adolescent girls: their
      role in health and disease.
AB  - BACKGROUND: Clinicians and investigators often do not appreciate the importance
      of vaginal microbiocoenosis and vaginal cytology in the health of prepubertal and
      adolescent girls. DATA SOURCES: Based on recent publications in human medicine
      and our own experience with vaginal cytology and microbiology in children and
      adolescent girls, we review the principles of vaginal microbiocoenosis and
      cytology and their roles in disease prevention in prepubertal and adolescent
      girls. RESULTS: The main role of vaginal microbiocoenosis and cytology in
      diagnosing as well as developing vulvovaginitis is demonstrated. Clinicians can
      identify states of vaginal health and disease by important well-known diagnostic
      tools, including vaginal cytology. Lactobacilli are infrequently observed in the
      prepubertal girls, but become more abundant in adolescent girls. Three basic
      types of vaginal smears are presented in addition to a classification of
      inflammatory urogenital diseases. Management of common types of vulvovaginitis is
      also considered. CONCLUSIONS: This essential shift in vaginal biocoenosis is
      important to prevent the growth of potentially pathogenic flora in the vagina.
      The detection of vaginal microbiocoenosis problems and recognition of changing
      cytology in vaginal development can provide helpful clues to identifying and
      preventing vaginal diseases in this pediatric population.

PMID- 20143207
TI  - Advances in diagnosis and treatment of pulmonary arterial hypertension in
      neonates and children with congenital heart disease.
AB  - BACKGROUND: This article aims to review recent advances in the diagnosis and
      treatment of pulmonary arterial hypertension in neonates and children with
      congenital heart disease. DATA SOURCES: Articles on pulmonary arterial
      hypertension in congenital heart disease were retrieved from PubMed and MEDLINE
      published after 1958. RESULTS: A diagnosis of primary (or idiopathic) pulmonary
      arterial hypertension is made when no known risk factor is identified. Pulmonary
      arterial hypertension associated with congenital heart disease constitutes a
      heterogenous group of conditions and has been characterized by congenital
      systemic-to-pulmonary shunts. Despite the similarities in histologic appearance
      of pulmonary vascular disease, there are differences between pulmonary arterial
      hypertension secondary to congenital systemic-to-pulmonary shunts and those with
      other conditions with respect to pathophysiology, therapeutic strategies, and
      prognosis. Revision and subclassification within the category of secondary
      pulmonary arterial hypertension based on pathophysiology were conducted to
      improve specific treatments. The timing of surgical repair is crucial to prevent
      and minimize risk of postoperative pulmonary arterial hypertension. Drug
      therapies including prostacyclin, endothelin-receptor antagonist,
      phosphodiesterase inhibitor, and nitric oxide have been evolved with promising
      results in neonates and children. CONCLUSIONS: Among the different forms of
      congenital heart diseases, an early correction generally prevents subsequent
      development of pulmonary arterial hypertension. Emerging therapies for treatment
      of patients with idiopathic pulmonary arterial hypertension also improve quality
      of life and survival in neonates and children with congenital heart disease
      associated with pulmonary arterial hypertension. Heart and lung transplantation
      or lung transplantation in combination with repair of the underlying cardiac
      defect is a therapeutic option in a minority of patients. Partial repair options
      are also beneficial in some selected cases. Randomized controlled trials are
      needed to evaluate the safety and efficacy of these therapies including survival
      and long-term outcome.

PMID- 20143209
TI  - Grown-up Kawasaki disease patients who have giant coronary aneurysms.
AB  - BACKGROUND: Many Kawasaki disease (KD) patients have reached adulthood in Japan.
      The current status of adult patients who have giant coronary aneurysms with KD is
      not well understood. METHODS: Medical records of 48 KD patients (33 males and 15
      females) with giant coronary aneurysms (maximum coronary artery internal diameter
      >8 mm) aged 20 years or over were retrospectively reviewed. RESULTS: The age of
      the patients at the diagnosis of KD ranged from 0.3 to 12.8 years (median 2.9
      years) and the age of the patients in this review ranged from 20.0 to 33.1 years
      (median 25.2 years). During the follow-up period, the maximum coronary artery
      internal diameter ranged from 8.2 to 30.0 mm (median 10 mm). Giant coronary
      aneurysms progressed to coronary artery stenosis and/or complete occlusion in 34
      (74%) of 46 patients. Coronary artery bypass graft surgery was performed in 9
      (19%) of 48 patients. Myocardial infarction occurred in 14 (31%) of 45 patients.
      Other complications or problems occurred in 5 patients with angina pectoris, low
      left ventricular ejection fraction, ventricular tachycardia, hemorrhagic cerebral
      infarction, or thyroid carcinoma respectively. In the patients followed up, 4
      dropped out. In addition, 1 patient succeeded in pregnancy and delivered a baby.
      CONCLUSIONS: Close attention should be paid to ventricular tachycardia in adult
      KD patients with giant coronary aneurysms, especially for those who have low left
      ventricular ejection fraction. To reduce the number of dropped out patients, it
      is important that the patients should be referred to a new doctor when they
      change their place of residence.

PMID- 20143210
TI  - Results of RS-99 protocol for childhood solid tumors.
AB  - BACKGROUND: Little was known about the therapeutic result of rhabdomyosarcomas
      (RMSs) and other malignant tumors until the end of the last century in China.
      Very few prospective clinical research results have been reported. We designed a
      RS-99 protocol under close cooperation of a multidisciplinary team including
      surgeons, radiologists, pathologists, and pediatric oncologists at Shanghai
      Children's Medical Center. This study aimed to improve the prognosis of childhood
      solid tumors and analyze the results of different tumors with the same protocol,
      including RMSs, the Ewing sarcoma family of tumors (ESFTs), and ex-cranial germ
      cell tumors (GCTs). METHODS: Sixty-six patients with malignant solid tumors [RMS
      (n=30), GCT (n=22), and ESFT (n=14)] were enrolled on the RS-99 protocol from
      October 1998 to October 2006. They were 34 girls and 32 boys aged 9 to 194
      months. The protocol involved surgery, radiotherapy and chemotherapy which
      included VCP (vincristine, cisdiaminedichloroplatinum, and cyclophosphamide) and
      IEV (etoposide, vincristine and ifosfamide) for the low-risk group, AVCP
      (adriamycin, vincristine, cisdiaminedichloroplatinum, and cyclophosphamide) and
      IEV for the intermediate-risk group and high-risk group. Peripheral blood stem
      cell transplantation was suggested for the high-risk group. Radiotherapy was only
      given for RMS and ESFT. Differences in survival between the groups were
      determined by comparison of entire survival curves and tested by the Kaplan-Meier
      method and the log-rank tests. RESULTS: The 5-year event-free survival (EFS) for
      the whole group (RMS, ESFT and GCT) was 60%. The 5-year EFS for children with RMS
      was 35% (95% CI 16-54), GCT was 79% (95% CI 70-88) and ESFT was 72% (95% CI 58
      86). The 5-year EFS showed that the patients with RMS in the retroperitoneum
      pelvis did not have a better result than those with tumors in other sites
      (P=0.604). The histological classification of RMS exerted prognostic influence on
      the estimated 5-year EFS (P=0.04). Tumor stage and risk group were also
      contributive to prognosis (P=0.008). For GCT patients, the primary sites of
      tumors and their histological classification did not influence the therapeutic
      result (P=0.814). The 5-year EFS was 100% in stage I and II versus 62% in stage
      III and IV patients (P=0.02). Because of the small number of patients, we did not
      analyze the prognostic factors for patients with ESFT. No organ failure or
      functional impairment occurred in the patients enrolled in the RS-99 protocol.
      One ESFT patient developed a second cancer. CONCLUSIONS: The RS-99 protocol is
      well tolerated and is reasonable for the 3 different tumors. Risk-based grouping
      protocol design is needed and the protocol for high risk RMS should be revised.

PMID- 20143211
TI  - Laparoscopic extensive colectomy with transanal Soave pull-through for intestinal
      neuronal dysplasia in 17 children.
AB  - BACKGROUND: Open colectomy has been preferred for intestinal neuronal dysplasia
      type B (IND) due to its low morbidity rate and good functional results. The aim
      of this study was to investigate the feasibility and results of laparoscopic
      colectomy with transanal Soave pull-through for the treatment of IND in children.
      METHODS: Seventeen infants and children suffering from IND were treated by
      laparoscopic extensive colectomy with transanal Soave pull-through. The diagnosis
      of IND was made via anorectal manometry, X-ray contrast enema, suction biopsies,
      and laparoscopic full-thickness biopsies with hematoxylin-eosin staining. The
      technique used four or five abdominal ports. The sigmoid, transverse, and right
      colon up to the last ileal cove were mobilized laparoscopically in the extended
      form of IND. A modified Soave's anastomosis was performed. The patients' data,
      surgical procedures, operative data, postoperative complications and clinical
      outcomes were analyzed. RESULTS: Five patients underwent laparoscopic left
      colectomy with modified transanal Soave procedures, and the other 12 were treated
      by laparoscopic subtotal colectomy and required a Deloyers' maneuver for the
      Soave pull-through. The proximal margin of barium stagnation in patients with
      left colectomy was restricted to the distal end of the descending colon, sigmoid
      colon, and that in patients with subtotal colectomy was restricted to the
      proximal end of the descending colon, transverse colon, hepatic flexure, and
      ascending colon. Postoperative complications included anastomotic leakage, severe
      perianal erosions, postoperative enterocolitis, and soiling. During a mean follow
      up of 4 years, bowel frequency was 4-10 times per day in 3 months postoperatively
      in patients with subtotal colectomy. The clinical results were good, with no
      stool incontinence or constipation. CONCLUSIONS: Laparoscopic procedure for left
      colectomy and subtotal colectomy with transanal Soave pull-through in infants and
      children with IND is safe, feasible, and effective. The location of barium
      stagnation in proximal margin may be used as a method to predict initially the
      proximal margin of the resected bowel segment.

PMID- 20143212
TI  - Intussusception in infants younger than 3 months: a single center's experience.
AB  - BACKGROUND: The diagnosis and treatment of intussusception is often confusing in
      infants aged younger than 3 months. This study aimed to discuss the particularity
      of diagnosis and treatment of intussusception in this age group. METHODS: From
      April 1983 to June 2008, 39 infants aged 3 months or younger who had been
      diagnosed with intussusception were treated and their clinical data were analyzed
      retrospectively. RESULTS: Of the 39 infants (29 boys and 10 girls), ages ranged
      from 12 hours to 3 months, with a mean age of 52.6 days. The duration from onset
      to admission ranged from 7 to 142 hours (mean 39.6 hours). Three infants had
      intrauterine intussusception and 36 postnatal intussusception. The 3 infants with
      intrauterine intussusception had typical presentations of complete ileus after
      birth. Gap type ileal atresia was found in surgery in 2 of the 3 infants and
      primary anatomosis was performed therapeutically. The other infant was found to
      have ileal separation and a patent proximal end with diffused meconium
      peritonitis. The patient died 2 days after primary anastomosis. Most infants with
      postnatal intussusception had two or more manifestations of the tetralogy, namely
      intermittent screaming, vomiting, bloody stool, and abdominal mass. In 23 infants
      who underwent pneumatic reduction, 17 had a successful reduction and 6 converted
      to open surgery. Surgery was indicated for 19 infants, with maneuver procedure in
      14. Meckel's diverticulum was noted as a leading cause in 2 infants, ileal
      duplication in 1 with necrosis of intussusceptum, and primary intussusception
      with lead point necrosis in 2. The 5 infants, on whom segmental resection was
      performed, underwent primary anastomosis. All infants with postnatal
      intussusception had a smooth recovery. CONCLUSIONS: Infants aged 3 months or
      younger may suffer from intussusception and most of them present with typical
      symptoms. Early diagnosis and treatment are needed for a good prognosis.
      Intrauterine intussusception may be an etiological factor for ileal atresia.

PMID- 20143213
TI  - The frequency of histologic lesion variability of the duodenal mucosa in children
      with celiac disease.
AB  - BACKGROUND: Celiac disease (CD) may cause changes throughout the gastrointestinal
      tract. Patchy distribution of duodenal mucosal lesions has been described in
      adults as well as in children. This study aimed to verify the concept and to
      evaluate the frequency of histologic lesion variability of the duodenal mucosa in
      Indian children with CD. METHODS: We enrolled 67 children prospectively who
      underwent upper gastrointestinal endoscopy because of positive tissue
      transglutaminase antibodies and biopsy as the final evaluation for suspected CD.
      Four biopsies were taken from the descending duodenum distal to the papilla, and
      duodenal bulb. The histologic lesions were classified according to the Oberhuber
      classification with modification proposed by our group. RESULTS: Forty-three CD
      children (64.2%) had a "mixed" type 3 lesion characterized by a different degree
      of villous atrophy at different biopsy sites. Eight children (11.9%) showed two
      different types of histologic lesions in the same patient at different biopsy
      sites. The overall variability of histologic lesion (variability in the grade of
      villous atrophy [type 3a, 3b, or 3c], and coexistence of villous atrophy and type
      2 lesion) was seen in 51 (76.1%) of the CD patients. CONCLUSIONS: Children with
      CD show a high frequency of variability of histologic lesions. Therefore,
      multiple endoscopic biopsy specimens should be obtained not only from the distal
      duodenum but also from the bulb.

PMID- 20143214
TI  - Human bocavirus in children with respiratory tract infection in Shanghai: a
      retrospective study.
AB  - BACKGROUND: Human bocavirus (HBoV) was first reported in 2005. The worldwide
      presence of HBoV in children with acute respiratory tract infection (ARTI) has
      been confirmed. This study aimed to understand the prevalence and clinical
      features of HBoV in children with ARTI in Shanghai and explore the causative
      implication of HBoV in ARTI. METHODS: We retrospectively reviewed the medical
      records of 349 hospitalized children with ARTI between November 2006 and January
      2007. From these children, 351 nasopharyngeal aspirate samples were collected;
      325 of the samples were obtained from those with community-acquired ARTI and 26
      from those with hospital-acquired ARTI. All samples were routinely screened for
      seven common respiratory viruses by immunofluorescence and further tested for
      HBoV by polymerase chain reaction. RESULTS: HBoV was detected in 16 (4.6%) of the
      351 samples, and it was the second most commonly detected virus after respiratory
      syncytial virus. Three (19%) HBoV-positive samples were dual infection with
      respiratory syncytial virus or parainfluenza virus type 3. Of the 325 children
      with community-acquired ARTI, HBoV was identified to be positive in 11 (3.4%), of
      whom 6 were diagnosed with pneumonia with patchy or interstitial infiltrates in
      the lung indicated by chest radiography, 3 with bronchitis, and 2 with bronchial
      asthma exacerbation with attendant lung infection. Out of the 26 children with
      nosocomial ARTI, 5 (19.2%) had bronchitis which was found to be HBoV positive
      without co-detection of other viruses. The HBoV-positive children were aged 1.7
      months to 43 months and their mean age was 13.7 months. Sixteen (100%) children
      had cough, 11 (68.8%) had wheezing, and 10 (62.5%) had fever. CONCLUSIONS: HBoV
      was circulating in Shanghai during the study period, and which was detected
      frequently in children with ARTI. HBoV was found to be associated with community
      acquired ARTI and may play a pathogenic role in nosocomial ARTI.

PMID- 20143215
TI  - Risk factors for mortality in neonatal tetanus: a 15-year experience in Sagamu,
      Nigeria.
AB  - BACKGROUND: Neonatal tetanus (NNT) is a major cause of newborn deaths especially
      in the developing world. While efforts aimed at eradicating NNT should be
      sustained, it is equally imperative to reduce death among affected infants.
      Therefore, the factors associated with mortality rate in this condition need to
      be studied. METHODS: The records of infants with NNT over a 15-year period (1991
      2005) were reviewed. A statistical comparison of the survivors and fatalities for
      relevant clinical characteristics was done, and the determinants of fatality rate
      were also determined using logistic regression. RESULTS: Ninety-six of 151
      newborns with NNT died, giving a mortality rate of 63.6%. The case fatality rate
      during the study period varied between 33.3% and 100%. More deaths occurred in
      the infants with low birth weight (P=0.004) within 1 day at the onset of symptoms
      (P<0.001), whose mothers aged 18 years or less (P=0.001) belonged to socio
      economic class V (P=0.001). Determinants of mortality in these infants with NNT
      included low socio-economic class (P=0.002), no antitetanus vaccination
      (P=0.006), presentation with spasms (P<0.001), and non-administration of anti
      tetanus serum during treatment (P=0.013). CONCLUSIONS: The mortality rate in
      infants with NNT remains signifi cantly high in Nigeria. Improved maternal anti
      tetanus vaccination and timely recognition and treatment of affected infants may
      jointly reduce the incidence and fatality rate of NNT.

PMID- 20143216
TI  - Bilateral congenital Morgagni-Larrey's hernia.
AB  - BACKGROUND: Congenital Morgagni-Larrey's hernia (CMLH) is rare and known to be
      associated with a high incidence of bilaterality and associated anomalies. This
      study aimed to review our patients with bilateral CMLH and evaluate their
      presentation, associated anomalies, diagnostic difficulties and therapy. METHODS:
      From January 1989 to December 2007, we treated 8 children with bilateral CMLH at
      our hospital. Their medical records were retrospectively reviewed for age, sex,
      symptoms, associated anomalies, diagnosis, operative findings, treatment and
      outcome. RESULTS: Among the 8 children, 4 were male and 4 female, with a mean age
      of 22.74 months (range: 0.93-108 months). Six of them sustained repeated attacks
      of pneumonia. In 5 children, bilaterality was diagnosed at surgery. Associated
      anomalies were observed in all children, including congenital heart disease in 5,
      Down's syndrome in 4, malrotation in 3, inguinal hernia in 2, umbilical hernia in
      1, and pyloric stenosis in 1. All of these children were operated on
      transabdominally. All of them did well postoperatively and on follow-up ranging
      from 1.5 years to 5 years (mean: 3 years), one had recurrence of the hernia as
      well as an incisional hernia. CONCLUSIONS: The diagnosis of bilateral CMLH may be
      difficult preoperatively, especially if one of the hernial sacs is empty. CT scan
      is valuable to diagnose bilateral hernias. To repair these hernias, we advocate a
      transabdominal approach, which allows easy reduction and inspection of contents,
      access and repair of bilateral hernias, and correction of associated malrotation
      if present.

PMID- 20143217
TI  - Vitamin A deficiency and wheezing.
AB  - BACKGROUND: Vitamin A deficiency may increase the responsiveness of the
      respiratory tract and increase the risk of respiratory tract infection, resulting
      in airway obstruction and wheezing. This study aimed to investigate the relation
      between vitamin A deficiency and infant wheezing. METHODS: Three ml venous blood
      samples were collected from 331 hospitalized children who suffered from wheezing
      to determine the serum vitamin A concentration and the relationship between
      vitamin A and some causative factors of wheezing. RESULTS: The severity of
      vitamin A deficiency was related to the course of wheezing. In the persistent
      wheezing group, 14 patients (34.1%) were diagnosed as having severe vitamin A
      deficiency and 16 patients (39%) having moderate vitamin A deficiency; among the
      acute wheezing group, 18 patients (16.4%) were diagnosed as having severe vitamin
      A deficiency and 32 patients (29%) having moderate vitamin A deficiency.
      Comparison of the two groups revealed that there was a significantly higher rate
      of moderate and severe vitamin A deficiency in the persistent wheezing group than
      in the acute wheezing group (P<0.01). The severity of vitamin A deficiency was
      related to the infants' wheezing severity. Severe vitamin A deficiency was found
      in 24 patients (47%) in the severe wheezing group and 8 (8%) in the mild and
      moderate wheezing groups. The rate of severe vitamin A deficiency was
      significantly higher in patients with severe wheezing than in those with mild and
      moderate wheezing (P<0.01). CONCLUSIONS: Serum vitamin A deficiency could be
      commonly found in infants with wheezing. The severity of vitamin A deficiency
      might be related to the course of wheezing and the infants' wheezing severity.

PMID- 20143218
TI  - Extracorporeal membrane oxygenation for the treatment of children with severe
      hemodynamic alteration in perioperative cardiovascular surgery.
AB  - BACKGROUND: This article summarizes the use of extracorporeal membrane
      oxygenation (ECMO) for the treatment of children with severe hemodynamic
      alteration in perioperative cardiovascular surgery. METHODS: Four children with
      congenital heart disease (CHD) (3 boys and 1 girl, aged 6 days to 4 years and
      weighing 2.8-15 kg) associated with severe heart failure and/or hypoxemia were
      treated with ECMO cardiopulmonary support in perioperative cardiovascular surgery
      between July 2007 and July 2008. We retrospectively analyzed the medical records
      of the 4 children. RESULTS: Of the 4 children, 2 survived and 2 died. The
      survivors were treated with venoarterial (VA) ECMO due to severe low output
      syndrome after arterial switch operation. They were weaned successfully from 22
      hour and 87-hour ECMO support, and discharged 20 days and 58 days after ECMO
      explantation, respectively. The other boy treated with venovenous ECMO died of
      severe hypoxemia and metabolic acidosis. The other girl with VSD, treated with VA
      ECMO because of failure to wean from cardiopulmonary bypass, died from
      irreversible heart failure 11 hours after ECMO explantation. The main
      complications in this series included pulmonary hemorrhage, blood tamponade,
      surgical site bleeding, hemolysis and hyperbilirubinemia. CONCLUSIONS: ECMO is an
      effective therapy for patients with severe heart failure in the perioperative
      cardiovascular surgery. The keys to successful ECMO are selection of indications,
      time to set up ECMO, and good management of complications during ECMO.

PMID- 20143219
TI  - Extreme penoscrotal transposition.

PMID- 20143220
TI  - Age-dependent presentation in children with attention deficit hyperactivity
      disorder.

PMID- 20143221
TI  - Prevention of adverse drug reactions in intensive care patients by personal
      intervention based on an electronic clinical decision support system.
AB  - OBJECTIVE: We investigated the effect of written drug information for senior
      clinicians on the incidence of drug-drug interactions (DDIs) and DDI-related
      adverse events in intensive care patients. DESIGN AND METHODS: A prospective
      controlled intervention cohort study was conducted in a medical intensive and
      intermediate care unit in a university hospital. From 1,062 consecutive intensive
      care patients, those 265 (control: 136, intervention: 129) with > or =8
      concurrently prescribed drugs were included in the study (to include high-risk
      patients with polypharmacy). The DDI information for senior clinicians during an
      intervention period of 3 months was based on a computerised clinical decision
      support system (CDSS) containing information on risk and management of 9,453 drug
      combinations. RESULTS: The number of patients with at least one DDI at the end of
      the respective study phase decreased by 18% (relative risk reduction) from 90
      (66%) patients in controls to 70 (54%) in the intervention group (p = 0.02). The
      relative risk of a patient suffering from at least one DDI-related adverse event
      decreased by 43% from 60 (44%) patients in controls to 32 (25%) in the
      intervention group (p < 0.01). Among these events, the incidence of QT(C)
      prolongation was reduced by 64% from 15 (11%) patients in the control group to 5
      (4%) in the intervention group (p = 0.04), and the incidence of hypokalemia by
      80% from 14 (10%) to 2 (2%, p < 0.01). CONCLUSION: Written drug information based
      on a CDSS considerably decreased DDIs and DDI-related adverse events in routine
      practice.

PMID- 20143222
TI  - Are small hospitals with small intensive care units able to treat patients with
      severe sepsis?
AB  - PURPOSE: To find out whether mortality from sepsis is influenced by the size of
      the hospital and of the intensive care unit (ICU). METHODS: In the Finnsepsis
      study, 470 patients with severe sepsis were identified. The present study is a
      retrospective subgroup analysis of the Finnsepsis study. Eighteen patients were
      excluded because of treatment in more than one ICU. We divided the 24 units into
      three groups based on hospital size and academic status. RESULTS: There were no
      significant differences between the ICU groups in terms of severity of illness.
      Overall, the hospital mortality rate was 29.2%. In post-operative patients, the
      hospital mortality rate was 22.9% for patients treated in large ICUs (including
      university and large non-university hospital ICUs) but 42.3% for patients treated
      in small ICUs (p = 0.045). In medical patients, no differences in outcomes were
      found. CONCLUSIONS: Treatment of surgical patients with severe sepsis in small
      ICUs was associated with increased mortality. Because of the relatively small
      sample size, further studies are needed to confirm or refute this association.

PMID- 20143223
TI  - A thiol-selective fluorogenic probe based on the cleavage of 4-methylumbelliferyl
      2',4',6'-trinitropheyl ether.
AB  - A new fluorescent probe 1,4-methylumbelliferyl-2',4',6'-trinitropheyl ether
      (Probe 1) was designed and synthesized. Probe 1 was a nonfluorescent compound and
      was synthesized via the one-step reaction of 4-methylumbelliferone (4-MU) with 1
      chloro-2,4,6-trinitrobenzene. Upon mixing with biothiols under neutral aqueous
      conditions, the 2,4,6-trinitrophenyl group of 1 was efficiently removed, and the
      emissive free dye 4-MU was released, hence leading to a dramatic increase in
      fluorescence emission of the reaction mixture. A good linear relationship was
      obtained from 0.1 to 4.0 micromol L(-1) for cysteine (Cys), from 0.1 to 3.0
      micromol L(-1) for homocysteine (Hcy), and from 0.2 to 3.0 micromol L(-1) for
      glutathione (GSH), respectively. The detection limits of Cys, Hcy, and GSH were
      24.3, 35.6, and 26.8 nmol L(-1), respectively. Furthermore, probe 1 was highly
      selective for biothiols without the interference of some biologically relevant
      analytes and has been applied to detecting biothiols in human serum samples.

PMID- 20143224
TI  - Screening of pesticides in blood with liquid chromatography-linear ion trap mass
      spectrometry.
AB  - In clinical or forensic toxicology, general unknown screening procedures are used
      to identify as many xenobiotics as possible, belonging to numerous chemical
      classes. We present here a general unknown screening procedure based on liquid
      chromatography coupled with use of a single linear ion trap mass spectrometer,
      and focus on the identification of pesticides and/or metabolites in whole blood.
      After solid-phase extraction (SPE), the compounds of interest were separated
      using a reversed-phase column and identified by the mass spectrometer operated
      first in the full-scan mass spectrometry (MS) mode, in the positive and negative
      polarities, followed by MS(2) and MS(3) scanning of ions selected in data
      dependent acquisition. The total scan time was 2.45 s. Two mass spectral
      libraries (MS(2) and MS(3)), each of 450 spectra, were created for the 320
      pesticides and metabolites detected after injection of pure solutions. Robustness
      of the spectra and matrix effects were studied and were satisfactory for the
      present application. Detection limits for the 320 compounds were studied by
      extracting 1 mL spiked blood at concentrations between 10 microg/L and 10 mg/L.
      If necessary, it was possible to decrease the detection limits of some compounds
      by 10-100-fold by scanning MS(2) in only one polarity, owing to a shorter total
      scan time. However, at the same time, the detection specificity decreased as no
      confirmation could be recorded in the following MS(3) scan and no information
      could be registered in the other polarity. So, in these rare cases, confirmation
      by another method was required.

PMID- 20143225
TI  - Polymer screening by radiofrequency glow discharge time-of-flight mass
      spectrometry.
AB  - The aim of this work is to optimise and evaluate radiofrequency glow discharge
      (RF GD) time-of-flight mass spectrometry (TOFMS) for identification of organic
      polymers. For this purpose, different polymers including
      poly[methylmethacrylate], poly[styrene], polyethylene terephthalate-co
      isophthalate and poly[alpha-methylstyrene] have been deposited on silicon wafers
      and the RF GD-TOFMS capabilities for qualitative identification of these
      polymeric layers by molecular depth profiling have been investigated. Although
      some molecular information using the RF continuous mode is available, the pulsed
      mode offers a greater analytical potential to characterise such organic coatings.
      Some formed polyatomic ions have proved to be useful to identify the different
      polymer layers, confirming that layers having similar elemental composition but
      different polymer structure could be also differentiated and identified.

PMID- 20143226
TI  - Evolution of Conus peptide genes: duplication and positive selection in the A
      superfamily.
AB  - A remarkable diversity of venom peptides is expressed in the genus Conus (known
      as "conotoxins" or "conopeptides"). Between 50 and 200 different venom peptides
      can be found in a single Conus species, each having its own complement of
      peptides. Conopeptides are encoded by a few gene superfamilies; here we analyze
      the evolution of the A-superfamily in a fish-hunting species clade, Pionoconus.
      More than 90 conopeptide sequences from 11 different Conus species were used to
      build a phylogenetic tree. Comparison with a species tree based on standard genes
      reveals multiple gene duplication events, some of which took place before the
      Pionoconus radiation. By analysing several A-conopeptides from other Conus
      species recorded in GenBank, we date the major duplication events after the
      divergence between fish-hunting and non-fish-hunting species. Furthermore,
      likelihood approaches revealed strong positive selection; the magnitude depends
      on which A-conopeptide lineage and amino-acid locus is analyzed. The four major A
      conopeptide clades defined are consistent with the current division of the
      superfamily into families and subfamilies based on the Cys pattern. The function
      of three of these clades (the kappaA-family, the alpha4/7-subfamily, and alpha3/5
      subfamily) has previously been characterized. The function of the remaining
      clade, corresponding to the alpha4/4-subfamily, has not been elucidated. This
      subfamily is also found in several other fish-hunting species clades within
      Conus. The analysis revealed a surprisingly diverse origin of alpha4/4
      conopeptides from a single species, Conus bullatus. This phylogenetic approach
      that defines different genetic lineages of Conus venom peptides provides a
      guidepost for identifying conopeptides with potentially novel functions.

PMID- 20143229
TI  - Main airborne Ascomycota spores: characterization by culture, spore morphology,
      ribosomal DNA sequences and enzymatic analysis.
AB  - The aim of this work was to identify the main allergy-related Ascomycetes fungal
      spores present in the atmosphere of Porto, using different and complementary
      techniques. The atmospheric sampling, performed in the atmosphere of Porto
      (Portugal) from August 2006 to July 2008, indicated Cladosporium, Penicillium,
      Aspergillus and Alternaria as the main fungal spore taxa. Alternaria and
      Cladosporium peaks were registered during summer. Aspergillus and Penicillium
      highest values were registered from late winter to early spring. Additionally,
      the Andersen sampler allowed the culture and isolation of the collected viable
      spores subsequently used for different identification approaches. The internal
      transcribed spacer region of the nuclear ribosomal repeat unit sequences of
      airborne Ascomycetes fungi isolates revealed 11 taxonomically related fungal
      species. Among the identified taxa, Penicillum and Aspergillus presented the
      highest diversity, while only one species of Cladosporium and Alternaria,
      respectively, were identified. All selected fungal spore taxa possessed
      phosphatase, esterase, leucine arylamidase and beta-glucosidase enzymatic
      activity, while none had lipase, cystine arylamidase, trypsin or beta
      glucuronidase activity. The association between the spore cell wall morphology,
      DNA-based techniques and enzymatic activity approaches allowed a more reliable
      identification procedure of the airborne Ascomycota fungal spores.

PMID- 20143230
TI  - Biofuel production in Escherichia coli: the role of metabolic engineering and
      synthetic biology.
AB  - The microbial production of biofuels is a promising avenue for the development of
      viable processes for the generation of fuels from sustainable resources. In order
      to become cost and energy effective, these processes must utilize organisms that
      can be optimized to efficiently produce candidate fuels from a variety of
      feedstocks. Escherichia coli has become a promising host organism for the
      microbial production of biofuels in part due to the ease at which this organism
      can be manipulated. Advancements in metabolic engineering and synthetic biology
      have led to the ability to efficiently engineer E. coli as a biocatalyst for the
      production of a wide variety of potential biofuels from several biomass
      constituents. This review focuses on recent efforts devoted to engineering E.
      coli for the production of biofuels, with emphasis on the key aspects of both the
      utilization of a variety of substrates as well as the synthesis of several
      promising biofuels. Strategies for the efficient utilization of carbohydrates,
      carbohydrate mixtures, and noncarbohydrate carbon sources will be discussed along
      with engineering efforts for the exploitation of both fermentative and
      nonfermentative pathways for the production of candidate biofuels such as
      alcohols and higher carbon biofuels derived from fatty acid and isoprenoid
      pathways. Continued advancements in metabolic engineering and synthetic biology
      will help improve not only the titers, yields, and productivities of biofuels
      discussed herein, but also increase the potential range of compounds that can be
      produced.

PMID- 20143231
TI  - Skating on thin ice: a study of the injuries sustained at a temporary ice skating
      rink.
AB  - In recent years, ice skating and temporary ice skating rinks have become
      increasingly popular. Regular elite competitors are known to be at risk of both
      acute and chronic injuries. It may be postulated that skaters at the temporary
      rinks are at high risk of acute injuries from falls due to both their lack of
      expertise and the inherent dangers of ice skating. Injuries sustained at skating
      rinks present a significant burden to local healthcare resources, in particular
      orthopaedic departments. For the first time, Cambridge hosted such a facility
      from November 24, 2007 through January 6, 2008. We sought to identify the most
      common injuries encountered and to quantify the orthopaedic burden. All Emergency
      Department or Fracture Clinic attendances for an eight-week period from the
      opening of the rink were investigated. Details of age, sex, injury and management
      were recorded for the 84 patients who sustained ice rink related injuries. A
      total of 85 injuries were recorded in 84 patients. Of these injuries 58% were
      fractures, of which 98% involved the upper limbs. Seven patients (8% of all
      injuries) required admission for operative fixation. On average, two injuries per
      day were seen in the Emergency Department or Fracture Clinic, with an average of
      one orthopaedic admission per week. It is evident that the ice rink in Cambridge
      has had an impact on local healthcare resources. The vast majority of injuries
      affected the upper limbs and were sustained following a fall on the out-stretched
      hand. We therefore encourage the education of skaters as to how to break their
      falls more safely and recommend the use of wrist protectors as a primary
      preventative measure.

PMID- 20143232
TI  - Coexistence of thyroid metastasis carcinoma in the background of HT and primary
      thyroid mucosa-associated lymphoid tissue B cell lymphoma in a thyroid gland.

PMID- 20143233
TI  - Human promoter mutations unveil Oct-1 and GATA-1 opposite action on Gfi1b
      regulation.
AB  - Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor
      essential for erythroid and megakaryocytic development. To better understand
      Gfi1b regulation and to know the implication of the level of expression of this
      gene in human pathology, we have searched for promoter punctual sequence
      variations in 214 patients with different hematological diseases. We found two
      previously unknown congenital mutations at evolutionary conserved GATA and
      octamer-binding (Oct) transcription factor sites. The Oct site mutation was also
      found in five relatives of the patient. The GATA motif mutation reduced promoter
      activity by 50% in vitro, while homozygous patients with the octamer site
      mutation showed a four-to-five times increase of Gfi1b RNA in platelets.
      Electrophoretic mobility shift analyses demonstrated that different protein
      complexes bind to both sites and that binding is reduced by the mutations.
      Finally, we found that GATA-1 and Oct-1 are the main components of each complex.
      This study provides evidences of a new mechanism for Gfi1b repression. This is
      also the first report of Gfi1b mutations with a functional implication; further
      investigation and follow-up will clarify the involvement of these mutations in
      hematological disease.

PMID- 20143235
TI  - Impact of using elastic stains for detection of venous invasion in the prognosis
      of patients with lymph node negative colorectal cancer.
AB  - PURPOSE AND METHODS: Patients with nodal negative colorectal cancer (CRC) suffer
      recurrent or metastatic disease in 40% of cases after surgical resection. To
      investigate a potential prognostic impact of vascular tumor infiltration, we
      retrospectively analyzed 185 nodal negative stage I and II CRC specimens for the
      presence of intra- and/or extramural venous invasion (V1IM/V1EM) using elastic
      stains of all tumor sections and correlated our findings with the clinical follow
      up. RESULTS: Venous invasion was observed in 43 (23.2%) patients by elastic
      stains compared with six (3.2%) using HE only (p < 0.05). Venous invasion was
      more common in stage II than in stage I tumors (28.1% versus 5.1%; p < 0.05).
      However, survival analyses showed no significant differences in 5-year survival
      rates comparing patients with and without venous invasion (68% and 71%, p =
      0.543) or patients with V1IM and V1EM (62% vs. 74%, p = 0.473), respectively.
      CONCLUSIONS: Our data emphasize the need for standardized criteria, including
      elastic stains, to reliably detect vascular invasion in CRC. Doing so, however,
      the prognostic impact of venous invasion in stage I and II CRC may be lower as
      previously anticipated.

PMID- 20143234
TI  - Freshwater elasmobranchs: a review of their physiology and biochemistry.
AB  - Only 5% of elasmobranch species live in freshwater (FW) compared to more than 40%
      of known teleost species. The factors affecting the poor penetration of
      elasmobranchs into FW environments are currently unknown, however, an important
      consideration may be the high urea requirement of many proteins in marine
      elasmobranchs. Urea is an important osmolyte in marine elasmobranchs and must be
      reduced in dilute environments. There are three identifiable stages in the
      successful colonization of FW. The euryhaline marine species freely entering and
      leaving FW represent the initial stage of FW colonization. In this group, there
      is an apparent inability to eliminate all urea due to protein integrity issues
      and this results in energy and nitrogen losses that may constrain growth and
      reproduction. The second stage is represented by those species that live entirely
      in FW but must also retain some urea. This group also suffers from the same
      constraints as the first group. These two groups have kidneys and sensory organs
      that more closely resemble strictly marine forms. The third and final stage is
      represented by the Potamotrygonid stingrays where the need for urea in FW has
      been eliminated. Consequently nitrogen and energy losses are reduced and those
      sections of the kidney needed for urea conservation have been eliminated. The
      driving force for such modifications is a reduction in urea levels and the
      concomitant saving of energy needed for urea synthesis. Other physiological
      adaptations associated with survival in FW include giving birth to live young,
      the capacity of sperm to be activated in freshwater and modifications of the
      electrosensory system to function in a low conductivity environment. The need for
      many anatomical, metabolic and physiological modifications for FW existence may
      constrain the rapidity and hence the frequency of FW colonization, compared to
      the situation in the more advanced osmoregulating teleosts. Once optimally
      adapted to FW, recolonization of sea water by elasmobranchs is problematic due to
      the loss of urea synthetic capacity and renal structures for urea retention.

PMID- 20143236
TI  - Choroidal melanoma in a 7-year-old child treated by trans-scleral local
      resection.
AB  - PURPOSE: To report a choroidal melanoma in a 7-year-old child treated by trans
      scleral local resection and adjuvant brachytherapy with a family history of
      neurofibromatosis type I (NF1) and cutaneous melanoma. PATIENT AND METHODS: A 7
      year-old child was referred for treatment of a choroidal tumor in her left eye
      with a differential diagnosis of melanoma, neurilemmoma, leiomyoma, and
      neurofibroma. Trans-scleral local resection and, subsequently, adjuvant
      brachytherapy were performed. RESULTS: Histopathology and immunohistochemistry of
      the specimen diagnosed an amelanotic melanoma of spindle cell type, with a
      moderately high number of mitoses (7/40 HPF). Multiplex ligation-dependent probe
      amplification (MLPA) analysis showed two copies of chromosome 3, three copies of
      the short arm of chromosome 6, and two copies of chromosome 8, strongly
      suggesting a good prognosis. Postoperative ophthalmic evaluation at 6 months
      showed no visible tumor and flat retina with visual acuity (VA) of 6/60.
      CONCLUSIONS: Trans-scleral local resection with adjuvant brachytherapy in
      children is possible using the same techniques as for adults. Although the follow
      up is short, our patient retained the eye with good vision and our cytogenetic
      studies allowed us to reassure the mother.

PMID- 20143238
TI  - High-grade breast cancers include both highly sensitive and highly resistant
      subsets to cytotoxic chemotherapy.
AB  - PURPOSE: We reported that breast cancers achieving pathological complete response
      (pCR) or progressive disease (PD) to neoadjuvant chemotherapy (NAC), which are
      considered exact opposites on the chemosensitivity spectrum, have certain
      clinicopathological features in common. To determine the highly sensitive and
      highly resistant subsets to cytotoxic chemotherapy, we evaluated predictive
      factors for pCR and PD to NAC, and assessed the similarities in these factors.
      METHODS: Subjects comprised 300 women with 304 stage II or III breast cancers
      treated with chemotherapy that was anthracycline-based, taxane, or both, followed
      by surgery between 2007 and 2008. We retrospectively evaluated pre-NAC
      clinicopathological features including chemotherapy regimen, clinical T stage,
      nuclear grade (NG), hormone receptor (HR) status, and human epidermal growth
      factor receptor-2 (HER2) status in pCR and PD, using univariate chi(2) testing
      and multivariate logistic regression analyses. RESULTS: Of 304 tumors, 30 (10%)
      achieved pCR and 22 (7%) showed PD to NAC. Multivariate analysis demonstrated
      that anthracycline plus taxane chemotherapy (P = 0.006), NG3 (P = 0.006), HR
      negativity (P = 0.013), and HER2-positivity (P = 0.010) were significant
      predictors of pCR, and T3-4 (P = 0.002) and NG3 (P = 0.010) were significant
      predictors of PD. CONCLUSIONS: High-grade breast cancers include both highly
      sensitive and highly resistant subsets to cytotoxic chemotherapy. Three factors
      can help discriminate between these subsets. HR-negative and HER2-positive can be
      predictive of high chemosensitivity. Advanced primary tumor stage can be
      predictive of high chemoresistance.

PMID- 20143237
TI  - Colonic potassium handling.
AB  - Homeostatic control of plasma K+ is a necessary physiological function. The daily
      dietary K+ intake of approximately 100 mmol is excreted predominantly by the
      distal tubules of the kidney. About 10% of the ingested K+ is excreted via the
      intestine. K+ handling in both organs is specifically regulated by hormones and
      adapts readily to changes in dietary K+ intake, aldosterone and multiple local
      paracrine agonists. In chronic renal insufficiency, colonic K+ secretion is
      greatly enhanced and becomes an important accessory K+ excretory pathway. During
      severe diarrheal diseases of different causes, intestinal K+ losses caused by
      activated ion secretion may become life threatening. This topical review provides
      an update of the molecular mechanisms and the regulation of mammalian colonic K+
      absorption and secretion. It is motivated by recent results, which have
      identified the K+ secretory ion channel in the apical membrane of distal colonic
      enterocytes. The directed focus therefore covers the role of the apical Ca2+ and
      cAMP-activated BK channel (KCa1.1) as the apparently only secretory K+ channel in
      the distal colon.

PMID- 20143239
TI  - Regulatory role of Six1 in the development of taste papillae.
AB  - The Six family genes encode homeobox transcription factors, and their deficiency
      leads to abnormal sensory organ structures. We analyzed the expression patterns
      of Six1 and its role in the morphogenesis of taste bud-bearing lingual papillae
      during mouse embryonic development. Six1 was expressed in the mesenchyme of the
      lateral lingual swellings at embryonic day (E) 11.5 and in the epithelium of
      fungiform papillae during E14.5-E17.5. In the posterior region of the tongue,
      Six1 expression appeared in the epithelial thickenings in the center of the
      dorsal surface at E13.5-E14.5 and was observed in the trench wall of
      circumvallate and foliate papillae at E15.5-postnatal day 0. Six1-deficient mice
      (Six1 (-/-)) showed distinct morphological changes: the fungiform papillae
      increased in size and number, and their distribution in the tongue differed from
      that of wild-type mice. The number of primordia of fungiform papillae marked by
      Shh and Wnt10b appeared to increase in Six1 ( -/- ). With regard to circumvallate
      papillae, more extensive invagination of epithelial thickenings, earlier
      formation of papillae, and stunted trenches were noted in Six1 ( -/- ); the
      expression of Shh was altered, consistent with these anomalies. The foliate
      papillae were elevated initially and showed stunted trenches in Six1 ( -/- ).
      Thus, the modulation of signaling events in Six1 ( -/- ) leads to the earlier
      formation of the gustatory papillae, the abnormal distribution of fungiform
      papillae, and malformed trenches in circumvallate and foliate papillae.

PMID- 20143240
TI  - Inducible regulatory T cells (iTregs) from recent-onset type 1 diabetes subjects
      show increased in vitro suppression and higher ITCH levels compared with
      controls.
AB  - CD4+CD25+(high) regulatory T cells (Tregs) play a pivotal role in the control of
      the immune response. A growing body of evidence suggests the reduced function of
      these cells in autoimmune diseases, including type 1 diabetes (T1D). Restoration
      of their function can potentially delay further disease development. In the
      present study, we have converted conventional effector T cells into induced Tregs
      (iTregs) in recent-onset (RO) T1D (n=9) and compared them with the same cells
      generated in controls (n=12) and in long-standing (LS) T1D subjects (n=9). The
      functional potential of in-vitro-generated Tregs was measured by using an in
      vitro proliferation assay. We noted that the suppressive potential of iTregs
      exceeded that of natural regulatory T cells (nTregs) only in the RO T1D subjects.
      We showed that iTregs from RO T1D subjects had increased expression of Foxp3, E3
      ubiquitin ligase (ITCH) and TGF-beta-inducible early gene 1 (TIEG1) compared with
      control and LS T1D subjects. We also expanded natural, thymically derived Tregs
      (nTregs) and compared the functional ability of these cells between subject
      groups. Expanded cells from all three subject groups were suppressive. RO T1D
      subjects were the only group in which both iTregs and expanded Tregs were
      functional, suggesting that the inflammatory milieu impacts in vitro Treg
      generation. Future longitudinal studies should delineate the actual contribution
      of the stage of disease to the quality of in-vitro-generated Tregs.

PMID- 20143241
TI  - Comparing Botox and Xeomin for axillar hyperhidrosis.
AB  - Recently, Xeomin, a novel botulinum toxin (BT) type A drug became available.
      Separation of complexing proteins reduced the size of its BT component, thus
      potentially affecting its tissue diffusion, adverse effect profile and
      therapeutic properties. We report the first use of Xeomin in an autonomic
      indication. A total of 46 patients (34 females, 12 males, age 32.7 +/- 13.2
      years, disease duration 14.2 +/- 12.0 years) with symmetric bilateral idiopathic
      axillar hyperhidrosis and a previously stable Botox treatment received 50 MU of
      BT in 5 ml of 0.9% NaCl/H(2)0 in each axilla. The patient, the injector and the
      observer were unaware of which axilla received Xeomin and which Botox. The
      therapeutic effect as measured from the BT application to the onset of its
      decrease lasted 3.2 +/- 1.4 months and was excellent in 89% and good in 11% of
      the patients. Side-to-side differences of the therapeutic effect (onset latency,
      extent, duration) were neither detectable by the patient nor by the physician.
      Injection site pain was identical and adverse effects did not occur. Xeomin can
      be used safely and effectively for the treatment of axillar hyperhidrosis. Size
      differences between Xeomin and Botox do not affect their therapeutic efficacy,
      tissue diffusion and adverse effect profile. Identical potency labelling allows
      easy exchange between both products.

PMID- 20143242
TI  - Efficiency of a mathematical model in generating CAD/CAM-partial crowns with
      natural tooth morphology.
AB  - The "biogeneric tooth model" can be used for computer-aided design (CAD) of the
      occlusal surface of dental restorations. From digital 3D-data, it automatically
      retrieves a morphology matching the natural surface left after preparation. This
      study evaluates the potential of this method for generating well-matched and well
      adjusted CAD/computer-aided manufacturing (CAM) fabricated partial crowns. Twelve
      models with partial crown preparations were mounted into an articulator. Partial
      crowns were designed with the Cerec 3D CAD software based on the biogeneric tooth
      model (Biog.CAD) and, for control, with a conventional data-based Cerec 3D CAD
      software (Conv.CAD). The design time was measured, and the naturalness of the
      morphology was visually assessed. The restorations were milled, cemented on the
      models, and the vertical discrepancy and the time for final occlusal adjustment
      were measured. The Biog.CAD software offered a significantly higher naturalness
      (up to 225 to 11 scores) and was significantly faster by 251 (+/- 78) s in
      designing partial crowns (p < 0.01) compared to Conv.CAD software. Vertical
      discrepancy, 0.52 (+/- 0.28) mm for Conv.CAD and 0.46 (+/- 0.19)mm for Biog.CAD,
      and occlusal adjustment time, 118 (+/- 132)s for Conv.CAD and 102 (+/- 77)s for
      Biog.CAD, did not differ significantly. In conclusion, the biogeneric tooth model
      is able to generate occlusal morphology of partial crowns in a fully automated
      process with higher naturalness compared to conventional interactive CAD
      software.

PMID- 20143243
TI  - Effect of two X-ray tube voltages on detection of approximal caries in digital
      radiographs. An in vitro study.
AB  - This study evaluated the effect of two different tube voltages on clinicians'
      ability to diagnose approximal carious lesions in digital radiographs. One
      hundred extracted teeth were radiographed twice at two voltage settings, 60 and
      70 kV, using a standardized procedure. Seven observers evaluated the radiographs
      on a standard color monitor pre-calibrated according to DICOM part 14.
      Evaluations were made at ambient light levels below 50 lx. All observations were
      analyzed with receiver operating characteristic curves. A histological
      examination of the teeth served as the criterion standard. A paired t test
      compared the effects of the two voltages. The significance level was set to p <
      0.05. Weighted kappa statistics estimated intra-observer agreement. No
      significant difference in accuracy of approximal carious lesion diagnosis was
      found between the two voltage settings. But five observers rated dentin lesions
      on radiographs exposed at 70 kV better than on radiographs exposed at 60 kV.
      Intra-observer agreement differed from fair to moderate. There was no significant
      difference in accuracy of approximal carious lesion diagnosis between digital
      radiographs exposed with 60 or 70 kV.

PMID- 20143245
TI  - Adult colo-colonic intussusception.

PMID- 20143246
TI  - A pilot study of topiramate dosages for migraine prophylaxis in an Asian
      population.
AB  - Topiramate is known to be efficacious in migraine prophylaxis, but its optimal
      dose has not been systematically studied in the Asian population. Here, we show
      that a fixed low dose of topiramate 25 mg/day is efficacious in migraine
      prophylaxis and also attest to advantages in terms of medication cost savings and
      more favourable side effect profile.

PMID- 20143247
TI  - No effect of pure oxygen inhalation on headache induced by glyceryl trinitrate.
AB  - Inhalation of hyperbaric oxygen has been used as an experimental treatment for
      migraine and pure oxygen is an established treatment for cluster headache.
      Intravenous glyceryl trinitrate (GTN) is an established headache model. In the
      present study the possibility of decreasing the headache by inhalation of pure
      oxygen was explored in a double-blind crossover design in 18 healthy subjects.
      Inhalation of air served as placebo. The subjects received intravenous GTN (0.25
      microg/kg/min) for 20 min. Headache was scored for 85 min. Sixteen of 18 (89%)
      subjects experienced GTN-induced headache after O(2)-inhalation and 17/18 (94%)
      experienced GTN-induced headache after air. The mean peak headache scores were
      1.9 and 2.4, respectively, on a numerical scale of 0-10. Oxygen inhalation did
      not have effect on GTN-induced headache, most likely because the theoretical
      decrease in NO levels, due to faster metabolism of NO, is too small to be
      detected in the GTN headache model.

PMID- 20143248
TI  - Bcl-2 family proteins and mitochondrial fission/fusion dynamics.
AB  - Mitochondria are dynamic organelles and can undergo regulated
      fission/fragmentation to produce smaller organelles or, alternatively, can
      undergo fusion to produce tubular or net-like mitochondrial structures. Although
      some of the molecules that control mitochondrial fission and fusion are known,
      new molecules and pathways that control this process continue to be discovered,
      suggesting that this process is more complex than previously appreciated. In
      addition to their crucial role in the regulation of apoptosis, recent studies
      have implicated members of the Bcl-2 family in maintenance of the mitochondrial
      network. Here, we discuss the mechanisms governing mitochondrial fission/fusion
      and summarize current knowledge concerning the role of Bcl-2 family members in
      regulating mitochondrial fission/fusion dynamics.

PMID- 20143249
TI  - Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell
      interactions.
AB  - The growth and guidance of primary olfactory axons are partly attributed to the
      presence of olfactory ensheathing cells (OECs). However, little is understood
      about the differences between the subpopulations of OECs and what regulates their
      interactions. We used OEC-axon assays and determined that axons respond
      differently to peripheral and central OECs. We then further purified OECs from
      anatomically distinct regions of the olfactory bulb. Cell behaviour assays
      revealed that OECs from the olfactory bulb were a functionally heterogeneous
      population with distinct differences which is consistent with their proposed
      roles in vivo. We found that the heterogeneity was regulated by motile
      lamellipodial waves along the shaft of the OECs and that inhibition of
      lamellipodial wave activity via Mek1 abolished the ability of the cells to
      distinguish between each other. These results demonstrate that OECs from the
      olfactory bulb are a heterogeneous population that use lamellipodial waves to
      regulate cell-cell recognition.

PMID- 20143251
TI  - A critical review of the roles of host lactoferrin in immunity.
AB  - Lactoferrin (Lf) is an essential element of innate immunity, which refers to
      antigen-nonspecific defense mechanisms that a host uses immediately or within
      hours after exposure to an antigen. Following infection, Lf is released from
      neutrophils (PMNs) in blood and inflamed tissues and, such as other soluble
      pattern-recognition receptors of the innate immunity, Lf recognizes unique
      microbial molecules called pathogen-associated molecular patterns (PAMPs): LPS
      from the gram-negative cell wall and bacterial unmethylated CpG DNA. However,
      unlike classical PAMPs receptors involved in the activation of immune cells, Lf
      may act either as a competitor for these receptors or as a partner molecule,
      depending on the physiological status of the organism. These immunomodulatory
      properties are explained by the ability of Lf to interact with proteoglycans and
      receptors on the surface of mammalian cells: cells of the innate (NK cells,
      neutrophils, macrophages, basophils, neutrophils and mast cells) and adaptive
      [lymphocytes and antigen-presenting cells (APCs)] immune systems, and also
      epithelial and endothelial cells. Through these interactions, Lf is able to
      modulate the migration, maturation and functions of immune cells, and thus to
      influence both adaptive and innate immunities. The understanding of the roles of
      the host-expressed Lf in immunity comes from in vivo and in vitro studies with
      exogenous Lf which, although informative, rarely reflect the pathological, or non
      pathological, conditions in the organism. In this review, the data from the
      literature will be critically analyzed in order to present a real picture of the
      regulatory roles of host Lf in immunity.

PMID- 20143250
TI  - The corticotropin releasing factor system in cancer: expression and
      pathophysiological implications.
AB  - Malignant tumors express multiple factors that have some role in the regulating
      networks supporting their ectopic growth. Recently, increased interest has been
      developing in the expression and biological role of the neuropeptides and
      receptors of the corticotropin releasing factor (CRF) system, the principal
      neuroendocrine mediator of the stress response, especially in the light of
      several R&D programs for small molecule antagonists that could present some
      anticancer therapeutic benefit. In the present article, we review the literature
      suggesting that the CRF system could be involved in the regulation of human
      cancer development. Potential implication in growth, metastasis, angiogenesis, or
      immune parameters via activation of locally expressed receptors could be
      clinically exploited by presenting targets of new therapeutic approaches.

PMID- 20143252
TI  - Life course social mobility and risk of upper aerodigestive tract cancer in men.
AB  - The aim of this study was to explore associations between social mobility and
      tumours of the upper aero-digestive tract (UADT), focussing on life-course
      transitions in social prestige (SP) based on occupational history. 1,796 cases
      diagnosed between 1993 and 2005 in ten European countries were compared with 1585
      controls. SP was classified by the Standard International Occupational Prestige
      Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium
      (M) and low (L). Time weighted average achieved and transitions between SP with
      nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H,
      L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals
      [95%-CIs] were estimated with logistic regression models including age,
      consumption of fruits/vegetables, study centre, smoking and alcohol consumption.
      The adjusted OR for the lowest versus the highest of three categories (time
      weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between
      cases and controls during working life. The downward trajectory H --> L gave an
      OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L
      trajectories ORs were also elevated relative to subjects with H --> H
      trajectories. The association between SP and UADT is not fully explained by
      confounding factors. Downward social trajectory during the life course may be an
      independent risk factor for UADT cancers.

PMID- 20143253
TI  - Electrospun nanofibers in oral drug delivery.
AB  - In order to enhance the delivery of drugs with limited absorption due to poor
      solubility/dissolution, approaches are being developed to improve the dissolution
      rates and solubility of drug molecules. These approaches include identification
      of water-soluble salts of parent drugs, preparation of stable amorphous drug
      formulations, inclusion of solubility-enhancing agents in the dosage form, and
      particle size reduction. Technologies to reduce drug particle size to sub
      micrometer range are being applied to product development more frequently.
      Electrospinning is being considered as one of the technologies which can produce
      nanosized drugs incorporated in polymeric nanofibers. In vitro and in vivo
      studies have demonstrated that the release rates of drugs from these nanofiber
      formulations are enhanced compared to those from original drug substance. This
      technology has the potential to be used for enhancing the oral delivery of poorly
      soluble drugs.

PMID- 20143254
TI  - Diallyl trisulfide-induced G2/M phase cell cycle arrest in DU145 cells is
      associated with delayed nuclear translocation of cyclin-dependent kinase 1.
AB  - PURPOSE: The present study was undertaken to gain insight into the molecular
      mechanism of G2/M phase cell cycle arrest resulting from treatment of DU145 cells
      with diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of
      garlic. METHODS: Cell cycle distribution was determined by flow cytometry.
      Immunoblotting was performed to determine protein expression. Overexpression of
      wild-type or mutant Cdc25C was achieved by transient transfection. Nuclear and
      cytoplasmic localization of cyclin B1 and cyclin-dependent kinase 1 (cdk1) was
      studied by immunoblotting. RESULTS: Exposure of DU145 human prostate cancer cells
      to DATS resulted in concentration- and time-dependent accumulation of G2/M phase
      cells, which correlated with down-regulation as well as increased S216
      phosphorylation of Cdc25C. Ectopic expression of wild-type or redox-insensitive
      mutants (C330S and C330S/C377S) or S216A mutant of Cdc25C failed to confer
      protection against DATS-induced G2/M phase arrest. The DATS-mediated G2/M phase
      cell cycle arrest was also independent of reduced complex formation between cdk1
      and cyclin B1, but correlated with delayed nuclear translocation of cdk1.
      CONCLUSION: The present study indicates that the DATS-mediated G2/M phase cell
      cycle arrest in DU145 cells results from differential kinetics of nuclear
      localization of cdk1 and cyclin B1.

PMID- 20143255
TI  - Dietary grape seed proanthocyanidins inhibit UVB-induced cyclooxygenase-2
      expression and other inflammatory mediators in UVB-exposed skin and skin tumors
      of SKH-1 hairless mice.
AB  - PURPOSE: The purpose of this study was to determine the chemopreventive mechanism
      of dietary grape seed proanthocyanidins (GSPs) against ultraviolet (UV) radiation
      induced skin tumor development in mice. METHODS: Six-to-seven-week-old SKH-1
      hairless mice were subjected to photocarcinogenesis protocol, and exposed to UVB
      radiation (180 mJ/cm(2)) three times/week for 24 weeks. Mice were fed a standard
      AIN76A control diet with or without supplementation with grape seed
      proanthocyanidins (GSPs; 0.2% or 0.5%, w/w). At the termination of the
      experiment, mice were sacrificed, and skin and skin tumor samples were harvested
      and subjected to the analysis of biomarkers related to inflammation using
      immunostaining, western blot analysis, ELISA and real-time PCR. RESULTS: Dietary
      GSPs inhibited UVB-induced infiltration of proinflammatory leukocytes and the
      levels of myeloperoxidase, cyclooxygenase-2 (COX-2), prostaglandin (PG) E(2),
      cyclin D1 and proliferating cell nuclear antigen (PCNA) in the skin and skin
      tumors compared to non-GSPs-treated UVB irradiated mouse skin and skin tumors.
      GSPs also significantly inhibited the levels of proinflammatory cytokines, tumor
      necrosis factor-alpha (P < 0.01), IL-1beta (P < 0.001) and IL-6 (P < 0.001), in
      UVB-exposed skin and skin tumors. CONCLUSION: The results from this study clearly
      suggest that dietary GSPs inhibit photocarcinogenesis in mice through the
      inhibition of UVB-induced inflammation and mediators of inflammation in mouse
      skin.

PMID- 20143257
TI  - Crystalline vs. ionic liquid salt forms of active pharmaceutical ingredients: a
      position paper.
AB  - Why not consider liquid salt forms of active pharmaceutical ingredients (APIs) as
      an alternative versatile tool in the pharmaceutical industry? Recent developments
      have shown that known APIs can be readily converted into ionic liquids and that
      these novel phases often possess different properties (e.g., improved
      solubilities and dissolution rates), which may have a direct impact on the
      pharmacokinetics and pharmacodynamics of the drug. They may also offer the
      potential of novel and more efficient delivery modes, as well as patent
      protection for each of the new forms of the drug. Since these pharmaceutically
      active ionic liquids represent a thermodynamically stable phase, they avoid the
      troublesome issues surrounding polymorphism and "polymorphic transformation." In
      some cases, an active cation and an active anion can be combined to produce a
      liquid possessing dual functionality. Here we examine and challenge the current
      industry reliance on crystalline APIs by discussing the breadth and potential
      impact of liquid salts as a possible approach to phase control.

PMID- 20143258
TI  - Direct and indirect influences of fate control belief, gambling expectancy bias,
      and self-efficacy on problem gambling and negative mood among Chinese college
      students: a multiple mediation analysis.
AB  - A multiple mediation model was proposed to integrate core concepts of the social
      axioms framework and the social cognitive theory in order to understand gambling
      behavior. It was hypothesized that the influence of general fate control belief
      on problem gambling and negative mood would be mediated by gambling-specific
      beliefs. Data from 773 Chinese college recreational gamblers were collected. The
      bootstrapping procedure was used to test the multiple mediation hypotheses.
      Significant indirect effects of fate control belief on problem gambling and
      negative mood through two gambling-specific mediators were found. Gambling
      expectancy bias was a more salient mediator than gambling self-efficacy. Fate
      control belief was also found to have a significant direct effect on negative
      mood. In general, a high level of general fate control belief was related to
      greater gambling expectancy bias and lower self-efficacy in resisting gambling,
      which were in turn related to problem gambling and negative mood. Limitations and
      implications of the study were discussed.

PMID- 20143259
TI  - Gambling on electronic gaming machines is an escape from negative self
      reflection.
AB  - An experiment tested whether thinking about oneself, particularly in negative
      terms, increases gambling intensity on Electronic Gaming Machines (EGMs). Forty
      male and 65 Female participants, aged 18-76 (M = 46.2, SD = 15.3), were recruited
      through newspaper advertisements to play a laptop simulated EGM in Hervey Bay,
      Queensland, Australia. Prior to play, subjects in the test conditions audio tape
      recorded 2 min of self reflection on either: (1) "things you like about
      yourself," or (2) "things you don't like about yourself." Immediately after the
      recordings, the subjects played an EGM that was programmed (rigged) with five
      wins in the first 20 spins, and indefinite losses thereafter. Participants
      gambled more intensively in terms of Average Bet Size, Number of Trials Played,
      and Speed of Betting in the negative self reflection condition compared to the
      control condition. The experiment supports the proposition that EGM gambling
      behavior is motivated by escape from negative self reflection.

PMID- 20143260
TI  - Toward meaningful evaluation of medical trainees: the influence of participants'
      perceptions of the process.
AB  - An essential goal of evaluation is to foster learning. Across the medical
      education spectrum, evaluation of clinical performance is dominated by subjective
      feedback to learners based on observation by expert supervisors. Research in non
      medical settings has suggested that participants' perceptions of evaluation
      processes exert considerable influence over whether the feedback they receive
      actually facilitates learning, but similar research on perceptions of feedback in
      the medical setting has been limited. In this review, we examine the literature
      on recipient perceptions of feedback and how those perceptions influence the
      contribution that feedback makes to their learning. A focused exploration of
      relevant work on this subject in higher education and industrial psychology
      settings is followed by a detailed examination of available research on
      perceptions of evaluation processes in medical settings, encompassing both
      trainee and evaluator perspectives. We conclude that recipients' and evaluators'
      perceptions of an evaluation process profoundly affect the usefulness of the
      evaluation and the extent to which it achieves its goals. Attempts to improve
      evaluation processes cannot, therefore, be limited to assessment tool
      modification driven by reliability and validity concerns, but must also take
      account of the critical issue of feedback reception and the factors that
      influence it. Given the unique context of clinical performance evaluation in
      medicine, a research agenda is required that seeks to more fully understand the
      complexity of the processes of giving, receiving, interpreting, and using
      feedback as a basis for real progress toward meaningful evaluation.

PMID- 20143261
TI  - Production of mouse chimeras by injection of embryonic stem cells into the
      perivitelline space of one-cell stage embryos.
AB  - Generation of mouse chimeras is useful for the elucidation of gene function. In
      the present report, we describe a new technique for the production of chimeras by
      injection of R1 embryonic stem (ES) cells into the perivitelline space of one
      cell stage mouse embryos. One-cell embryos are injected with 2-6 ES cells into
      the perivitelline space under the zona pellucida without laser-assistance. Our
      embryo culture experiments reveal that ES cells injected at the one-cell stage
      embryo start to be incorporated into the blastomeres beginning at the 8-cell
      stage and form a chimeric blastocyst after 4 days. We have used this approach to
      successfully produce a high rate of mouse chimeras in two different mouse genetic
      backgrounds permitting the establishment of germ line transmitters. This method
      allows for the earlier introduction of ES cells into mouse embryos, and should
      free up the possibility of using frozen one-cell embryos for this purpose.

PMID- 20143262
TI  - FSI analysis of the coughing mechanism in a human trachea.
AB  - The main physiological function of coughing is to remove from the airways the
      mucus and foreign particles that enter the lungs with respirable air. However, in
      patients with endotracheal tubes, further surgery has to be performed to improve
      cough effectiveness. Thus, it is necessary to analyze how this process is carried
      out in healthy tracheas to suggest ways to improve its efficacy in operated
      patients. A finite element model of a human trachea is developed and used to
      analyze the deformability of the tracheal walls under coughing. The geometry of
      the trachea is obtained from CT of a 70-year-old male patient. A fluid structure
      interaction approach is used to analyze the deformation of the wall when the
      fluid (in this case, air) flows inside the trachea. A structured hexahedral-based
      grid for the tracheal walls and an unstructured tetrahedral-based mesh with
      coincident nodes for the fluid are used to perform the simulations with the
      finite element-based commercial software code (ADINA R&D Inc.). Tracheal wall is
      modeled as an anisotropic fiber reinforced hyperelastic solid material in which
      the different orientation of the fibers is introduced. The implantation of an
      endotracheal prosthesis is simulated. Boundary conditions for breathing and
      coughing are applied at the inlet and at the outlet surfaces of the fluid mesh.
      The collapsibility of a human trachea under breathing and coughing is shown in
      terms of flow patterns and wall stresses. The ability of the model to reproduce
      the normal breathing and coughing is proved by comparing the deformed shape of
      the trachea with experimental results. Moreover the implantation of an
      endotracheal prosthesis would be related with a decrease of coughing efficiency,
      as clinically seen.

PMID- 20143263
TI  - Quantification of hemodynamics in abdominal aortic aneurysms during rest and
      exercise using magnetic resonance imaging and computational fluid dynamics.
AB  - Abdominal aortic aneurysms (AAAs) affect 5-7% of older Americans. We hypothesize
      that exercise may slow AAA growth by decreasing inflammatory burden, peripheral
      resistance, and adverse hemodynamic conditions such as low, oscillatory shear
      stress. In this study, we use magnetic resonance imaging and computational fluid
      dynamics to describe hemodynamics in eight AAAs during rest and exercise using
      patient-specific geometric models, flow waveforms, and pressures as well as
      appropriately resolved finite-element meshes. We report mean wall shear stress
      (MWSS) and oscillatory shear index (OSI) at four aortic locations (supraceliac,
      infrarenal, mid-aneurysm, and suprabifurcation) and turbulent kinetic energy over
      the entire computational domain on meshes containing more than an order of
      magnitude more elements than previously reported results (mean: 9.0-million
      elements; SD: 2.3 M; range: 5.7-12.0 M). MWSS was lowest in the aneurysm during
      rest 2.5 dyn/cm(2) (SD: 2.1; range: 0.9-6.5), and MWSS increased and OSI
      decreased at all four locations during exercise. Mild turbulence existed at rest,
      while moderate aneurysmal turbulence was present during exercise. During both
      rest and exercise, aortic turbulence was virtually zero superior to the AAA for
      seven out of eight patients. We postulate that the increased MWSS, decreased OSI,
      and moderate turbulence present during exercise may attenuate AAA growth.

PMID- 20143256
TI  - Stability of protein pharmaceuticals: an update.
AB  - In 1989, Manning, Patel, and Borchardt wrote a review of protein stability
      (Manning et al., Pharm. Res. 6:903-918, 1989), which has been widely referenced
      ever since. At the time, recombinant protein therapy was still in its infancy.
      This review summarizes the advances that have been made since then regarding
      protein stabilization and formulation. In addition to a discussion of the current
      understanding of chemical and physical instability, sections are included on
      stabilization in aqueous solution and the dried state, the use of chemical
      modification and mutagenesis to improve stability, and the interrelationship
      between chemical and physical instability.

PMID- 20143265
TI  - Which method to deliver hyperthermic intraperitoneal chemotherapy with
      oxaliplatin? An experimental comparison of open and closed techniques.
AB  - BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) achieves good
      results in selected patients with peritoneal carcinomatosis. There are two main
      procedures to deliver this therapy: the open abdomen and the closed abdomen
      techniques. A true comparison of the two techniques has never been performed. The
      aim of this study was to compare blood and abdominal tissue concentrations of
      oxaliplatin after open and closed techniques to deliver HIPEC. METHODS: Nine pigs
      underwent HIPEC at 42-43 degrees C for 30 min with oxaliplatin (400 mg/m(2))
      according to two techniques: closed (three animals) or open (six animals). The
      open technique used either an external heater with a pump (three animals) or an
      intra-abdominal heating cable (three animals) to achieve hyperthermia.
      Temperature homogeneity, systemic absorption, and abdominal tissue mapping of the
      penetration of oxaliplatin with each technique were studied. Two additional pigs
      underwent hyperthermia with dyes instead of oxaliplatin to depict the
      distribution of the liquid within the abdomen with both techniques. RESULTS:
      Hyperthermia was satisfactory with both techniques. The closed technique achieved
      higher temperatures within the diaphragmatic area, while the open technique
      obtained higher temperatures in the mid and lower abdomen (P < 0.001 for both
      comparisons). The systemic absorption of oxaliplatin was higher with the open
      technique (P < 0.04 for all comparisons), as was the accumulation within the
      abdominal cavity. The operating time for the two techniques was not greatly
      different. CONCLUSIONS: Intraperitoneal hyperthermia can be achieved with both
      techniques. The open technique had far higher systemic absorption and abdominal
      tissue penetration of oxaliplatin than the closed technique.

PMID- 20143264
TI  - Rehabilitation treatments for adults with behavioral and psychosocial disorders
      following acquired brain injury: a systematic review.
AB  - This review was aimed at systematically investigating the treatment efficacy and
      clinical effectiveness of neurobehavioral rehabilitation programs for adults with
      acquired brain injury and making evidence-based recommendations for the adoption
      of these rehabilitation trainings. Using a variety of search procedures, 63
      studies were identified and reviewed using a set of questions about research
      methods, treatments, results and outcomes for the 1,094 participants. The 63
      studies included treatments falling into three general categories: approaches
      based on applied behavior analysis, interventions based on cognitive-behavior
      therapy (CBT), and comprehensive-holistic rehabilitation programs (CHRPs).
      Considerable heterogeneity exists in the reviewed literature among treatment
      methods and within reported sample subjects. Despite the variety of
      methodological concerns, results indicate that the greatest overall improvement
      in psychosocial functioning is achieved by CHRP that can be considered a
      treatment standard for adults with behavioral and psychosocial disorders
      following acquired brain injury. Both approaches based on applied behavior
      analysis and CBT can be said to be evidence-based treatment options. However,
      findings raise questions about the role of uncontrolled factors in determining
      treatment effects and suggest the need for rigorous inclusion/exclusion criteria,
      with greater specification of theoretical basis, design, and contents of
      treatments for both interdisciplinary-comprehensive approaches and single-case
      methodologies.

PMID- 20143266
TI  - Can breast MRI predict axillary lymph node metastasis in women undergoing
      neoadjuvant chemotherapy.
AB  - BACKGROUND: Axillary lymph node status provides important staging information. We
      sought to evaluate the predictive value of breast magnetic resonance imaging
      (MRI) in detecting axillary lymph node metastases prior to initiation of
      neoadjuvant chemotherapy (NAC) and in detecting residual lymph node metastases
      after NAC in women found to be node positive prior to NAC. METHODS: Women
      underwent breast MRI with axillary evaluation prior to initiation of NAC and
      again after completion of NAC. Pathologic confirmation of lymph node status was
      confirmed by sentinel lymph node biopsy (SLNB), image-guided axillary fine-needle
      aspiration (FNA)/core biopsy, or axillary lymph node dissection. We evaluated the
      sensitivity, specificity, and negative and positive predictive values of MRI in
      detecting axillary node involvement. RESULTS: Seventy-four women completed NAC
      and underwent surgery. Sensitivity of MRI in detecting axillary node involvement
      prior to NAC was 64.7% and specificity was 100%, with positive and negative
      predictive values of MRI of 100% and 77.8%, respectively. Sensitivity and
      specificity of MRI to identify residual pathologic axillary lymph node disease
      following NAC were 85.7% and 89%, respectively, while the positive and negative
      predictive values were 92% and 80.9%, respectively. CONCLUSION: Breast MRI has
      moderate sensitivity and high specificity for predicting axillary lymph node
      status prior to NAC. In patients found to be node positive prior to NAC, MRI was
      able to predict with moderate sensitivity and specificity whether residual nodal
      disease was present. The accuracy of MRI is not adequate to obviate either the
      need for staging by sentinel node biopsy or the need for completion axillary
      dissection in women determined to be node positive prior to NAC.

PMID- 20143267
TI  - Liver resection for multimodal treatment of breast cancer metastases:
      identification of prognostic factors.
AB  - BACKGROUND: Liver resection (LR) within a multimodal treatment concept of hepatic
      metastases (HM) that results from breast cancer has been controversially
      discussed. The aim of this study was to evaluate the outcome of LR in patients
      with hepatic breast cancer metastases. METHODS: Prospectively collected data from
      41 consecutive patients who underwent LR for HM between 1999 and 2008 were
      analyzed retrospectively. Univariate and multivariate analyses were performed to
      assess potential prognostic factors. RESULTS: Segmental resection was performed
      in 46% and major hepatectomy in 54% of patients. The postoperative mortality rate
      was 0%. At a median follow-up of 34 months, 26 patients were alive. The median
      and 5-year overall survival rates after LR were 58 months and 48%, respectively.
      The median and 5-year disease-free survivals were 34 months and 31%,
      respectively. The intrahepatic recurrence-free 5-year survival was 62%. The
      median survival from time of diagnosis of HM was 79 months. The positive
      resection margin as well as a disease-free interval between the treatment of the
      primary tumor and the diagnosis of HM < 1 year were independent predictors of
      overall survival. CONCLUSIONS: LR of hepatic breast cancer metastases within a
      multimodal treatment concept is a safe procedure in well-selected patients. Both
      a short time interval to the development of HM and positive resection margins
      after LR are strongly associated with worse long-term survival.

PMID- 20143268
TI  - New operative surgical concept of two fascial layers enveloping the recurrent
      laryngeal nerve.
AB  - BACKGROUND: Avoiding recurrent laryngeal nerve (RLN) injury is aided by a precise
      anatomical understanding of the RLN before entry into the larynx where it is at
      greatest risk. METHODS: A literature review and study of 977 RLNs at operation
      have been used to describe the last 2 cm of the anatomical course of the
      extralaryngeal RLN. RESULTS: The tertiary branches of the inferior thyroid artery
      pass in a superficial vascular fascial layer anterolateral to the RLN. The
      tubercle of Zuckerkandl and the superior parathyroid glands lie within this
      superficial vascular fascial covering layer. The RLN lies on a deeper layer of
      more fibrous tissue, the ligament of Berry. In all 977 RLNs, the RLN was
      sandwiched between an anterolateral vascular layer and a medial layer, the
      ligament of Berry. CONCLUSIONS: The site of greatest risk during thyroidectomy to
      the RLN is in the 2-cm course of the extralaryngeal nerve above the trunk of the
      inferior thyroid artery where tension forms an artificial genu of the nerve. Once
      the superficial vascular fascial and Berry's ligament layers are released, the
      nerve falls back into the tracheoesophageal groove and adopts a serpiginous
      appearance, indicating completeness of the dissection of the lobe from the
      lateral trachea and division of the ligament of Berry.

PMID- 20143269
TI  - Condom use with female sex workers among male clients in Sichuan Province, China:
      the role of interpersonal and venue-level factors.
AB  - Commercial sex work has re-emerged as a widespread industry since China started
      economic reforms in the 1980s. This study examined the role of interpersonal and
      venue-level factors in commercial sex male clients' (CSMCs) condom use with
      female sex workers (FSWs) in China. Given the heterogeneity of commercial sex
      industry in China, this study also aimed to explore how these factors function
      differently by social ranks of commercial sex work frequented by CSMCs. A cross
      sectional survey was conducted with 601 CSMCs in Sichuan province, China. Human
      immunodeficiency virus (HIV) prevalence in this sample was 1.7%. In addition to
      the individual characteristics, interpersonal factor was measured by the
      frequency of FSWs taking the initiative in condom use and providing condoms.
      Venue-level factor was assessed by the frequency of the managers of commercial
      sex venues communicating condom use policies and the frequency of condom
      availability in commercial sex venues. The primary behavioral outcome was
      consistent condom use with FSWs. Multivariate logistic regression models revealed
      that consistent condom use with FSWs was significantly associated with
      interpersonal (adjusted odds ratio (AOR), 1.62; 95% confidence interval (CI),
      1.38, 1.90) and venue-level factors (AOR, 1.98; 95% CI, 1.40, 2.80). Moreover,
      the associations between interpersonal and venue-level factors and consistent
      condom use were moderated by social ranks of commercial sex work frequented by
      the male clients. The present study findings underscore the need for
      comprehensive HIV prevention approaches that integrate individual, interpersonal,
      and venue-level factors to reduce HIV risk behaviors among CSMCs in China.

PMID- 20143270
TI  - Examining the temporal relationship between criminal justice involvement and
      sexual risk behaviors among drug-involved men.
AB  - Although criminal justice involvement has repeatedly been associated with human
      immunodeficiency virus (HIV)/sexually transmitted infection prevalence and sexual
      risk behaviors, few studies have examined whether arrest or incarceration
      uniquely contributes to sexually risky behavior. We examined the temporal
      relationship between criminal justice involvement and subsequent sexual HIV risk
      among men in methadone maintenance treatment in New York City. A random sample of
      356 men was interviewed at baseline (time 1), 6-month (time 2), and 12-month
      (time 3) follow-ups. Propensity score matching, negative binomial, and multiple
      logistic regression were used to isolate and test the effect of time 2 arrest and
      incarceration on time 3 sexual risk behaviors. Incidence of time 2 criminal
      justice involvement was 20.1% for arrest and 9.4% for incarceration in the prior
      6 months. Men who were arrested at time 2 demonstrated increased number (adjusted
      incidence rate ratio [IRR] = 1.62; 95% confidence intervals [CI] = 1.11, 2.37)
      and proportion (IRR = 1.36; 95% CI = 1.07, 1.72) of unprotected vaginal sex acts
      at time 3. Men incarcerated at time 2 displayed increased number (IRR = 2.07; 95%
      CI = 1.23, 3.48) and proportion (IRR = 1.45; 95% CI = 1.06, 1.99) of unprotected
      vaginal sex acts at time 3. Within this sample of drug-involved men, arrest and
      incarceration are temporally associated with and may uniquely impact successive
      sexual risk-taking. Findings underscore the importance of HIV prevention
      interventions among individuals with low-intensity criminal justice involvement.
      Developing prevention efforts aimed at short-term incarceration, community
      reentry, and alternatives to incarceration settings will address a large and
      under-researched segment of the criminal justice population. Alternative
      approaches to current criminal justice policy may result in public health
      benefits.

PMID- 20143271
TI  - Multiple transmission pathways and disease dynamics in a waterborne pathogen
      model.
AB  - Multiple transmission pathways exist for many waterborne diseases, including
      cholera, Giardia, Cryptosporidium, and Campylobacter. Theoretical work exploring
      the effects of multiple transmission pathways on disease dynamics is incomplete.
      Here, we consider a simple ODE model that extends the classical SIR framework by
      adding a compartment (W) that tracks pathogen concentration in the water.
      Infected individuals shed pathogen into the water compartment, and new infections
      arise both through exposure to contaminated water, as well as by the classical
      SIR person-person transmission pathway. We compute the basic reproductive number
      ([Symbol: see text](0)), epidemic growth rate, and final outbreak size for the
      resulting "SIWR" model, and examine how these fundamental quantities depend upon
      the transmission parameters for the different pathways. We prove that the endemic
      disease equilibrium for the SIWR model is globally stable. We identify the
      pathogen decay rate in the water compartment as a key parameter determining when
      the distinction between the different transmission routes in the SIWR model is
      important. When the decay rate is slow, using an SIR model rather than the SIWR
      model can lead to under-estimates of the basic reproductive number and over
      estimates of the infectious period.

PMID- 20143272
TI  - Duodenal fistula after elective gastrectomy for malignant disease : an italian
      retrospective multicenter study.
AB  - BACKGROUND: Duodenal fistula (DF) after gastrectomy continues to be a life
      threatening problem. We performed a retrospective multicenter study analyzing the
      characteristics of DF after elective gastrectomy for malignant disease. METHODS:
      Three thousand seven hundred eighty-five patients who had undergone gastrectomy
      with duodenal stump in 11 Italian surgical units were analyzed. RESULTS: Sixty
      eight DFs occurred, with a median frequency of 1.6% and a mortality rate of 16%.
      Complications were mainly septic but fistulas or bleeding of surrounding organs
      accounted for about 30%. Reoperation was performed in 40% of patients. We
      observed a correlation between mortality and age (hazard ratio 1.09; 95% CI 1.00
      1.20) and serum albumin (hazard ratio 0.90; 95% CI 0.83-0.99). The appearance of
      further complications was associated with reoperation (P < 0.001) and death (P =
      0.054), while the preservation of oral feeding was related to DF healing (P <
      0.001). CONCLUSIONS: This paper represents the largest series ever published on
      DF and shows that its features have changed in the last 20 years. DF alone no
      longer leads to death and some complications observed in the past have
      disappeared, while new ones are emerging. Nowadays, medical therapy is preferred
      and surgery is indicated only in cases of abdominal sepsis or bleeding.

PMID- 20143273
TI  - Adequate length of the distal resection margin in rectal cancer: from the
      oncological point of view.
AB  - INTRODUCTION: The distal resection margin (DRM) has been considered an important
      factor for the oncological outcome of rectal cancer surgery. However, the optimal
      distal margins required to achieve safe oncological outcome remains to be
      controversial. MATERIAL AND METHODS: More recently, as circumferential resection
      margin or mesorectal margin has been additionally reported to be more important
      factors predicting patient outcome than the distal mucosal margin, a re
      evaluation of the impact of DRM on patient outcome is needed. RESULTS: The extent
      of distal tumor spread is known to be influenced by a variety of factors such as
      tumor location, lymph node metastasis, and tumor size. DRM might affect survival
      more than a local recurrence. Because distal intramural tumor spread rarely
      exceeds 1 to 2 cm in most rectal cancers, and local control and survival do not
      seem to be compromised by shorter distal resection margins, the generally
      accepted practice is to aim for a 2-cm DRM. However, in the recent trend of
      curative resection after preoperative chemoradiotherapy, with an otherwise
      favorable tumor such as well-differentiated tumor and no lymph node metastasis, a
      DRM at < or =1 cm does not necessarily portend a poor prognosis. In cases with
      preoperative chemoradiotherapy, distal resection margins need to be evaluated
      individually. DISCUSSION: It has been suggested that down-staging of low-lying
      rectal cancers after preoperative radiation might well include the pathological
      clearance of distal intramural microscopic spread. Moreover, the measurement of
      DRM varies with respective study, making it difficult to compare. CONCLUSION: We
      need an applicable intraoperative method to accurately measure distal resection
      margin, enabling comparative outcome.

PMID- 20143274
TI  - Reconstruction of the common hepatic artery at the time of total pancreatectomy
      using a splenohepatic bypass.
AB  - Arterial involvement by a periampullary adenocarcinoma is often a
      contraindication for resection, since an R0 resection cannot be achieved. This is
      usually observed in cases with involvement of the superior mesenteric artery.
      Involvement of the common hepatic artery, however, requires a bypass procedure if
      the gastroduodenal artery was divided during the resection. In such cases, the
      splenic artery can be used as an inflow-source provided that there is no stenosis
      of the celiac trunk and the splenic blood flow is preserved via the short gastric
      arteries. We describe a technique used in four cases for the reconstruction of
      the common hepatic artery following a segmental resection of this vessel en bloc
      with a periampullary tumor during pancreatectomy. The inflow is maintained by a
      splenohepatic bypass using the splenic artery.

PMID- 20143275
TI  - Differential sensitivity of A2A and especially D2 receptor trafficking to cocaine
      compared with lipid rafts in cotransfected CHO cell lines. Novel actions of
      cocaine independent of the DA transporter.
AB  - The effects of low and high concentrations of cocaine have been studied in vitro
      on the trafficking of plasma membrane A(2A) and D(2) immunoreactivities in
      previously characterized A(2A)-D(2) CHO cell lines. Receptor double
      immunofluorescence staining was performed with D(2) and A(2A) antibodies, planar
      lipid rafts immunolabeling with biotinylated cholera toxin subunit B and membrane
      invaginations with an anti-caveolin-1 antibody. A computer-assisted image
      analysis demonstrated a substantial and highly significant rise of membrane
      associated D(2) immunoreactivity (IR) after 8 h of exposure to a low
      concentration of cocaine (150 nM). At this low concentration of cocaine, there
      was also an increase of membrane associated A(2A) immunoreactivity but smaller
      and less significant. However, this increase became considerably larger and
      highly significant at 150 microM at which concentration the rise of D(2)
      immunoreactivity had begun to disappear. It may be suggested that an allosteric
      action of cocaine at 150 nM on the D(2) receptors may primarily increase the
      insertion of D(2) monomers, homomers and also of a subpopulation of A(2A)-D(2)
      heteromers from the cytoplasm into the plasma membrane due to the conformational
      change induced by cocaine in the D(2) receptor. The planar lipid rafts and the
      caveolae are only affected by the higher concentrations of cocaine. It is
      proposed that changes in D(2) and A(2A)-D(2) trafficking induced by allosteric
      actions of cocaine at D(2) receptors may contribute to the alterations of D(2)
      signaling found in cocaine abusers.

PMID- 20143276
TI  - Circulating tumor cells in colorectal cancer: past, present, and future
      challenges.
AB  - Recent advances in immunomagnetic separation and flow cytometry have made the
      detection and characterization of circulating tumor cells (CTC) a reality. This
      technology has already demonstrated prognostic significance in breast and
      prostate cancer. In the current review, we will review the historical and current
      data regarding the enumeration and identification of CTC in colorectal cancer.
      With immunomagnetic separation techniques, CTC can reliably and reproducibly be
      identified within 1 to 2 cells in a 7.5 mL sample of peripheral blood.
      Prospective studies have demonstrated a significant adverse impact on survival
      with the presence of > or = 3 CTC per 7.5 mL blood. Approximately one quarter of
      patients with metastatic disease will be categorized in this poor prognosis
      group. In addition, change in number of cells on treatment has prognostic
      significance. While CTC enumerated through immunomagnetic separation are a clear
      prognostic factor for patients with mCRC, the future challenge is to study
      whether treatment decision-making should be impacted by their level. Low cell
      yield in mCRC is a potential hinderance to answering these important clinical
      questions at present. CTC can also be isolated and studied with flow cytometry,
      FISH, and RT-PCR, allowing real-time assessment of tumor biology. Future advances
      in this field will improve both the detection and manipulation of these cells.
      Improvements in detection and characterization of CTC will hopefully lead to
      refinement of the surgical and chemotherapeutic treatment of colorectal cancer.

PMID- 20143277
TI  - What does food mean to black men?

PMID- 20143278
TI  - A systematic review of screening questionnaires for obstructive sleep apnea.
AB  - PURPOSE: Obstructive sleep apnea (OSA) may lead to life-threatening problems if
      it is left undiagnosed. Polysomnography is the "gold standard" for OSA diagnosis;
      however, it is expensive and not widely available. The objective of this
      systematic review is to identify and evaluate the available questionnaires for
      screening OSA. SOURCE: We carried out a literature search through MEDLINE,
      EMBASE, and CINAHL to identify eligible studies. The methodological validity of
      each study was assessed using the Cochrane Methods Group's guideline. PRINCIPAL
      FINDINGS: Ten studies (n = 1,484 patients) met the inclusion criteria. The Berlin
      questionnaire was the most common questionnaire (four studies) followed by the
      Wisconsin sleep questionnaire (two studies). Four studies were conducted
      exclusively on "sleep-disorder patients", and six studies were conducted on
      "patients without history of sleep disorders". For the first group, pooled
      sensitivity was 72.0% (95% confidence interval [CI]: 66.0-78.0%; I(2) = 23.0%)
      and pooled specificity was 61.0% (95% CI: 55.0-67.0%; I(2) = 43.8%). For the
      second group, pooled sensitivity was 77.0% (95% CI: 73.0-80.0%; I(2) = 78.1%) and
      pooled specificity was 53.0% (95% CI: 50-57%; I(2) = 88.8%). The risk of
      verification bias could not be eliminated in eight studies due to insufficient
      reporting. Studies on snoring, tiredness, observed apnea, and high blood pressure
      (STOP) and STOP including body mass index, age, neck circumference, gender (Bang)
      questionnaires had the highest methodological quality. CONCLUSION: The existing
      evidence regarding the accuracy of OSA questionnaires is associated with
      promising but inconsistent results. This inconsistency could be due to studies
      with heterogeneous design (population, questionnaire type, validity). STOP and
      STOP-Bang questionnaires for screening of OSA in the surgical population are
      suggested due to their higher methodological quality and easy-to-use features.

PMID- 20143279
TI  - Standardizing anesthesia medication drawers using human factors and quality
      assurance methods.
AB  - PURPOSE: In Calgary, each of the three acute-care adult hospitals had different
      anesthetic medication carts with their own type and layout of anesthetic
      medications. A number of anesthesiologists moved among the different sites,
      increasing the potential for medication errors. The objective of this study was
      to identify the anesthetic medications to include and to determine how they
      should be grouped and positioned in a standardized anesthesia medication cart
      drawer. METHODS: A standardized list of medications was established. Next, the
      anesthesia medication cart drawer was filled and photographed, and a jigsaw
      puzzle was made from the photograph. Anesthesiologists and anesthesia assistants
      arranged the jigsaw pieces into an ideal drawer. Participants verbalized their
      rationale for the position of each puzzle piece. Results were collated and
      analyzed. A mock drawer was developed and reviewed by department members, and
      minor modifications were made. RESULTS: A final standardized medication drawer
      (content and positioning) was developed over 30 months, with agreement from
      anesthesiologists (n = 12) and anesthesia assistants (n = 3) at the three
      hospitals. Guidelines for placing each medication in the drawer included grouping
      them according to order of use, frequency of use, similarity of action, severity
      of harm from misuse, and lack of similar appearance. A finalized template was
      used for a standardized drawer and installed in every operating room of the three
      hospitals. CONCLUSION: Implementation of the standardized medication drawer is
      expected to reduce the likelihood of medication errors. Future research should
      include testing the clinical implications of this standardization and applying
      the methodology to other areas.

PMID- 20143280
TI  - [Children with bronchial asthma: effects of an integrated health-care programme].
AB  - BACKGROUND: On 1 (st) June 2005 a contract for an integrated health-care
      programme (IHP) for infants, children and juveniles with bronchial asthma (2 to
      18-year-olds) was concluded. Care providers are specialised paediatricians
      (PaedNetz Bayern) and two rehabilitation clinics; cost payers are two Bavarian
      health insurances (DAK, TK). METHODS: With a questionnaire (Q5) the following 5
      items were collected every 12 months: absent days, hospital admissions, days at
      hospital, emergency visits and use of relievers. To estimate the adherence to the
      German asthma guidelines, every 6 months the symptoms, therapy and consecutive
      procedures were recorded. RESULTS: At the end of 2008, 1280 patients had
      participated; the follow-up showed a significant reduction of the Q5 items 2
      years later. The comparison of patients who had already participated for at least
      12 months in the IHP with patients who have just started to participate showed
      significant reductions (p < 0.05) of all Q5 items between 54 % and 85 %.
      According to the guidelines - 6 months after starting the IHP - in 25 % a more
      intense therapy would be helpful. This percentage declines to 17 % at 24 months
      (p < 0.05). CONCLUSION: Children and juveniles with bronchial asthma who are
      treated by specialised paediatricians and rehabilitation clinics by means of an
      integrated health-care program show a significant reduction of absent days,
      emergency visits, hospitalisations, days in hospital and use of relievers.

PMID- 20143281
TI  - [Effect of asbestos fibre dust exposures on lung function--a systematic review].
AB  - Asbestos-induced lung diseases are in addition to skin diseases and hearing
      impairment due to noise the most frequent occupational diseases. In this
      connection, many questions arise. They particularly refer to the fine diagnostics
      and the compensation in case of early stages. This systematic review questions
      the prevailing practice of getting medical expert opinions. It was shown that
      already pleural plaques and low stages of lung fibrosis due to asbestos are
      significantly associated with symptoms of chronic obstructive bronchitis,
      lymphocytic alveolitis and significant functional restrictions, i. e. FVC, FEV
      (1) and TLC restrictions, gas exchange impairments (P ((A-a),O2), P (a,O2)),
      diffusion disorders (D (L,CO)) and an obstructive ventilation pattern (FEV
      (1)/FVC, FEF values, D (L,CO)). The asbestos fibre dose shows some relation to
      reductions of FVC, FEV (1), FEF values, and D (L,CO). Only about half of the
      asbestos-induced functional impairments are related to radiological (inclusive
      CT) findings. To a lesser degree, these findings also apply to exposed people
      without pathological chest X-ray findings. The diffusion capacity reduction, at
      first still within the reference range, is an early indication of a lung lesion
      caused by asbestos fibres. The same applies to spiroergometric parameters (P ((A
      a),O2), V (E/)V (O2), V (D)/V (T)). Reduced lung compliance can also be
      determinable at an early asbestosis stage. The results of literature research
      confirmed by statements of international groups of experts indicate continuous
      pathophysiological processes due to asbestos fibres deposited in peripheral
      airways and in the lung. These processes are neither radiologically nor
      histopathologically detectable and occur with a chronic lymphocytic alveolitis.
      Therefore, diagnostics of asbestos-induced non-malignant lung and pleural changes
      require comprehensive lung function tests. The outcome may help to estimate the
      probable remaining life span.

PMID- 20143282
TI  - [The lung disease of Thomas Bernhard--reality and fiction].

PMID- 20143283
TI  - [The impact of viruses in lower respiratory tract infections of the adult. Part
      III: therapy and prevention].
AB  - In industrialized countries respiratory tract infections are one of the most
      common reasons for medical consultations. It is assumed that almost one third of
      these infections include the lower respiratory tract (LRTI), e. g. acute
      bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD),
      community- or hospital-acquired pneumonia and influenza. Due to a lack of
      sufficient and valid investigations to prove the presence of respiratory viruses
      their impact in the pathogenesis of lower respiratory tract infection has
      probably been underestimated for a long time. Therefore, there might have been
      many cases of unnecessary antibiotic treatment, especially in cases of acute
      bronchitis or acute exacerbations of COPD, because of an assumed bacteriological
      cause. With the introduction of more sensitive investigational procedures, such
      as polymerase chain reaction, it is possible to sufficiently prove respiratory
      viruses and therefore illuminate their role in the pathogenesis of lower
      respiratory tract infections of the adult. We have reviewed the current
      literature on the impact of viruses in lower respiratory tract infections to
      elucidate the role of viruses in the pathogenesis of lower respiratory tract
      infections. The preceding parts of this series provided an introduction to the
      frequently found viruses, pathogenesis, and diagnostic procedures (part I) as
      well as common viral infections of the lower respiratory tract (part II). The
      present 3 (rd) part deals with therapy for and prevention of viral LRTI.

PMID- 20143284
TI  - [Management of a new influenza A/H1N1 virus pandemic within the hospital.
      Statement of the German Society of Pneumology].
AB  - This update summarized the hospital experience from the first wave of the new
      influenza A/H1/N1 pandemic.

PMID- 20143285
TI  - [Benchmarking of radiological departments--starting point for successful process
      optimization].
AB  - INTRODUCTION: Continuous optimization of the process of organization and medical
      treatment is part of the successful management of radiological departments. The
      focus of this optimization can be cost units such as CT and MRI or the
      radiological parts of total patient treatment. Key performance indicators for
      process optimization are cost- effectiveness, service quality and quality of
      medical treatment. The potential for improvements can be seen by comparison
      (benchmark) with other hospitals and radiological departments. Clear definitions
      of key data and criteria are absolutely necessary for comparability. There is
      currently little information in the literature regarding the methodology and
      application of benchmarks especially from the perspective of radiological
      departments and case-based lump sums, even though benchmarking has frequently
      been applied to radiological departments by hospital management. AIM AND CONTENT:
      The aim of this article is to describe and discuss systematic benchmarking as an
      effective starting point for successful process optimization. This includes the
      description of the methodology, recommendation of key parameters and discussion
      of the potential for cost-effectiveness analysis. The main focus of this article
      is cost-effectiveness (efficiency and effectiveness) with respect to cost units
      and treatment processes.

PMID- 20143286
TI  - X-Ray protective clothing: does DIN 6857-1 allow an objective comparison between
      lead-free and lead-composite materials?
AB  - PURPOSE: The validity of DIN 6857-1 to establish lead equivalence for protective
      clothing is evaluated by Monte Carlo simulations and measurements. MATERIALS AND
      METHODS: Commercially available protective clothing made of lead, lead-free and
      lead-composite materials has been tested regarding its protective efficacy. The
      analysis has been performed on the one hand in accordance with the test
      conditions described in the manufacturing standard DIN EN 61331-3 and on the
      other hand following the new DIN 6857-1 standard. Additionally, measurements have
      been carried out under simulated patient conditions by using an Alderson-Rando
      phantom. RESULTS: Following DIN EN 61331-3, the lead-free protective clothing
      achieved the required protective efficacy only at a restricted tube-voltage
      range. The test according to DIN 6857-1 showed that the protective criteria were
      fulfilled only by one lead-composite apron, but not by the three lead-free aprons
      examined. Thus, in order to guarantee the same protection as lead between 50 and
      120 kV, the conditions of DIN 6857-1 must be fulfilled. CONCLUSION: A
      modification of DIN EN 61331-3 to account for secondary radiation is strongly
      advised in the case of lead-free materials. In summary, most of the protective
      lead-free aprons in use should be used with care, particularly for examinations
      with a high dose.

PMID- 20143287
TI  - [Evaluation of an interactive breath-hold control system in CT-guided lung
      biopsy].
AB  - PURPOSE: In this study we assessed the effect of an interactive breath-hold
      control system on procedure time and technical success in transthoracic CT-guided
      lung biopsies. MATERIALS AND METHODS: In 36 patients (4 female, 32 male, mean age
      65 years; range 33 - 88) with a pulmonary nodule, we performed CT-guided biopsy
      using a 18G Tru-cut needle (Cardinal Health, Dublin, UK) in a 64 row dual-source
      CT scanner (Somatom Definition, Siemens, Forchheim, Germany) using intermittent
      imaging of the needle. In half of the patients (2 female, 16 male, mean age 67
      years), an interactive breath-hold control system (IBC) (Mayo Clinic Medical
      Devices, USA) was applied. No additional device was used in the control group.
      RESULTS: The biopsy was visually successful in all patients. The diameter of the
      target lesion was comparable in both groups (IBC: 30 +/- 19 mm; control: 28 +/-
      15 mm). The number of imaging steps was significantly smaller (p < 0.05) and the
      intervention time was significantly shorter (p < 0.05) in the IBC group (IBC: 9
      +/- 5 steps 17 +/- 10 min; control: 13 +/- 5 steps 26 +/- 12 min). CONCLUSION:
      Application of the IBC unit reduced the intervention time and radiation exposure
      in CT-guided Tru-cut biopsy of pulmonary nodules.

PMID- 20143288
TI  - [Thrombosed intraorbital hemangioma as etiology of acute intraorbital pain].

PMID- 20143289
TI  - [Endovascular therapy of a pulmonary artery pseudoaneurysm hemorrhage in
      pulmonary space occupying lesion of unknown origin].

PMID- 20143291
TI  - Perisesaccharides A-E, new oligosaccharides from the root barks of Periploca
      sepium.
AB  - Five new oligosaccharides, named perisesaccharides A-E (1- 5), were isolated from
      the root barks of Periploca sepium. Their structures were elucidated by NMR and
      HRESIMS data. The absolute configurations of these compounds were determined by a
      combination of X-ray diffraction analysis, modified Mosher's method, circular
      dichroism spectroscopy, and acid hydrolysis. The boat conformation of oleandronic
      acid delta-lactone was reported for the first time.

PMID- 20143290
TI  - Increase of plasma insulin by racecadotril, an inhibitor of enkephalinase, in
      Wistar rats.
AB  - Racecadotril is known as an inhibitor of enkephalinase. Increase of plasma
      insulin by racecadotril has been observed in rats while the mechanism of the
      action remains obscure. In the present study, intravenous injection of male
      Wistar rats with racecadotril significantly decreased blood glucose levels.
      However, this effect of racecadotril was not modified by naloxone at the dose
      sufficient to block opioid receptors. Thus, the blood glucose-lowering action of
      racecadotril might be through an endogenous opioid independent mechanism.
      Otherwise, we found that C-peptide content was also raised by racecadotril in
      parallel with the increase of insulin in Wistar rats. Thus, the blood glucose
      lowering action of racecadotril was related to insulin secretion, but not through
      the inhibition of plasma insulin degradation. In addition, racecadotril showed no
      direct effect on insulin secretion in isolated islets or cultured HIT-T15 beta
      cells. The increase of plasma insulin and blood glucose-lowering action induced
      by racecadotril were reduced by pretreatment with atropine and enhanced by
      physotigmine. Direct inhibition of cholinesterase was not observed in brain
      homogenates treated with racecadotril. Moreover, actions of racecadotril were
      significantly reduced in rats receiving hemicholinium-3 at a sufficient dose to
      decrease endogenous acetylcholine. Activation of cholinergic tone is possibly
      involved in the blood glucose-lowering effect of racecadotril. Our results
      suggested that racecadotril increased insulin secretion to lower blood glucose
      mainly via regulation of parasympathetic tone in Wistar rats.

PMID- 20143292
TI  - Grapefruit oil attenuates adipogenesis in cultured subcutaneous adipocytes.
AB  - We investigated the effects of different essential oils on adipogenesis in rat
      subcutaneous adipocytes. Subcutaneous preadipocytes were cultured in Dulbecco's
      Modified Eagle Medium (DMEM) containing insulin, transferrin, fibroblast growth
      factor, dexamethasone, indomethacin, fetal bovine serum, and an essential oil at
      37 degrees C in 5% CO2 to induce their differentiation. After 7 days, the number
      of viable cells and the amount of triglycerides accumulated in the cells were
      determined. Differentiation markers such as the enzymatic activity of glycerol-3
      phosphate dehydrogenase (GPDH) and the expression of GPDH and peroxisome
      proliferator-activated receptor gamma (PPAR gamma) genes were also measured, as
      well as the intracellular Ca2+ levels. We found that grapefruit oil inhibited the
      accumulation of triglycerides in a dose-dependent manner at concentrations of 50
      to 400 microg/mL. Furthermore, it suppressed the expression of GPDH and caused a
      70% decrease in the enzymatic activity of GPDH at a concentration of 50
      microg/mL. Grapefruit oil also caused a nearly 2-fold increase in the
      intracellular concentration of Ca2+ and suppressed the expression of PPAR gamma
      genes. Our results demonstrate that grapefruit oil efficiently inhibits
      adipogenesis in cultured subcutaneous preadipocytes and adipocytes.

PMID- 20143293
TI  - New secoiridoid glucosides from Ligustrum lucidum induce ERK and CREB
      phosphorylation in cultured cortical neurons.
AB  - Two new secoiridoid glucosides, namely iso-oleonuezhenide (1) and methyloleoside
      7-ethyl ester (2), along with five known ones, oleonuezhenide (3), nuezhenide
      (4), oleuropein (5), G13 (6), and jaspolyside methyl ester (7), were isolated
      from the fruits of Ligustrum lucidum. Their structures were assigned based on 1H
      NMR, 13C-NMR, and 2D-NMR analyses, in combination with HR-MS experiments and the
      comparison with literature data of related compounds, as well as on chemical
      experiments. We have examined the ability of these compounds to activate ERK and
      CREB in cultured cortical neurons. Our studies demonstrate that compound 1
      induces ERK and CREB phosphorylation in primary cortical neurons in a dose- and
      temporal-dependent manner, suggesting its bioactivity on neurons.

PMID- 20143294
TI  - Cellular mechanisms of the anticancer effects of the lichen compound usnic acid.
AB  - The lichen compound usnic acid is used for its antimicrobial activities in
      cosmetic products and is also a component of slimming agents. Its effect against
      cancer cells was first noted over 30 years ago. In this study possible mechanisms
      of this effect were investigated using two human cell lines, the breast cancer
      cell line T-47D and the pancreatic cancer cell line Capan-2. Pure (+)-usnic acid
      from CLADONIA ARBUSCULA and (-)-usnic acid from ALECTORIA OCHROLEUCA were shown
      to be equally effective inhibitors of DNA synthesis, with IC (50) 4.2 microg/mL
      and 4.0 microg/mL for (+) and (-)-usnic acid against T-47D, and 5.3 microg/mL and
      5.0 microg/mL against Capan-2, respectively. Flow cytometric analysis confirmed
      the inhibited entry into the S-phase and showed reduction in cell size. Classical
      apoptosis, as assessed by TUNEL staining, was not observed. Necrosis, measured by
      LDH release, was seen only in Capan-2 after exposure for 48 hours. Staining with
      the mitochondrial dye JC-1 demonstrated dose-dependent loss of mitochondrial
      membrane potential following treatment with usnic acid in both cell lines. In
      conclusion, usnic acid had a marked inhibitory effect on growth and proliferation
      of two different human cancer cell lines and led to loss of mitochondrial
      membrane potential. Cell survival was little affected; late necrosis was seen in
      one of the cell lines. No difference was noted between the two enantiomers.

PMID- 20143295
TI  - Two new triterpene glycosides from Centella asiatica.
AB  - Phytochemical investigation of the leaves of Centella asiatica resulted in the
      isolation and characterization of eight triterpenes and/or saponins [which were
      characterized as 23- O-acetylmadecassoside (1), asiatic acid (2), madecassic acid
      (3), asiaticoside C (4), asiaticoside F (5), asiaticoside (6), madecassoside (7),
      and 23- O-acetylasiaticoside B (8)] together with sitosterol 3-O-beta-glucoside (
      9), stigmasterol 3- O- beta-glucoside (10), and querectin-3- O-beta-D-glucuronide
      (11). A new ursane-derived saponin (23- O-acetylmadecassoside) and a new oleanane
      derived saponin (23- O-acetylasiaticoside B) were found as well. Structure
      elucidation was done by using spectroscopic techniques (HR-ESI-MS, 1D and 2D
      NMR), chemical methods, and comparative literature studies.

PMID- 20143296
TI  - Enhancement of insulin release from the beta-cell line INS-1 by an ethanolic
      extract of Bauhinia variegata and its major constituent roseoside.
AB  - Plants of the genus Bauhinia are used in several countries worldwide for the
      treatment of diabetes, and several related species have been shown to have
      hypoglycaemic effects in vivo in both normoglycaemic and alloxan- and
      streptozotocin-treated animal models. In this study, the insulin-secreting cell
      line INS-1 was used to examine the effects of the crude ethanolic extract of
      leaves of B. variegata L. var. Candida Voidt and its major metabolite (6 S,7 E,9
      R)-9-hydroxymegastigma-4,7-dien-3-one-9- beta-glycopyraroside (roseoside) on
      insulinotropic activity. The crude extracts and the major metabolite were shown
      to increase insulin secretion in a dose-dependant manner.

PMID- 20143297
TI  - Refining perforator selection for DIEP breast reconstruction using transit time
      flow volume measurements.
AB  - Transit time flow volume has been used in cardiac surgery to assess small vessel
      flow characteristics. This study examines the usefulness of transit time flow
      volume (TTFV) in assessing perforator vessels in deep inferior epigastric artery
      perforator (DIEP) flap harvesting. The purpose of this study was to evaluate the
      correlation among computed tomographic angiography (CTA), intraoperative TTFV
      measurements, and hand-held Doppler signals in identifying perforators. Ten
      consecutive free DIEP breast reconstructions were prospectively evaluated using
      CTA to identify abdominal wall perforators. Intraoperatively, perforating vessels
      >1 mm in diameter were evaluated with a conventional hand-held 8-MHz Doppler and
      a TTFV measurement device. Vessel location was correlated with preoperative CTA .
      Waveform patterns and TTFV measurements were recorded for each vessel and
      correlated with both CTA and hand-held Doppler signals. Of the 54 perforators
      identified, TTFV showed arterial flow waveforms in 15 of 16 perforators
      identified by CTA and in 2 of the remaining 38 vessels. The sensitivity and
      specificity of TTFV in identifying arterial perforators were 94 and 95%,
      respectively. In contradistinction, hand-held Doppler was misleading in 70% of
      vessels. TTFV distinguishes arterial from venous waveforms in vessels that appear
      arterial by hand-held Doppler signals. CTA and TTFV are highly correlated, and
      the use of TTFV may prevent poor perfusion seen in some DIEP flaps.

PMID- 20143298
TI  - Free groin flap applications in the pediatric population.
AB  - The popularity of the groin flap has gradually decreased because of the
      disadvantages related to its short pedicle and technically demanding harvesting.
      We have summarized our experience with free groin flap applications in the
      pediatric population, which were performed by the same surgeon between 2004 and
      2007. A total of 10 free groin flap transfers were performed in patients aged 3
      to 13 years. Nine of the patients were operated on because of contractures of the
      extremities (six lower, three upper), and one patient was operated on for facial
      contour augmentation. The total duration of the operation was estimated to be
      between 2.6 and 6.1 hours (mean: 4.1 hours). A revision of the anastomosis was
      performed in two patients (20%), and in one of these patients (50%) partial flap
      failure was seen. Flap defatting via liposuction was performed in four patients
      (40%) in the late postoperative period. In our opinion, donor site morbidity
      comes into prominence particularly in the pediatric population, and we think that
      free groin flap should be the first choice of free flap for suitable cases in
      this group of patients.

PMID- 20143299
TI  - Osteo-periosteal-cutaneous flaps of the medial femoral condyle: a valuable
      modification for selected clinical situations.
AB  - In situations of bony nonunions with poor skin coverage, transplantation of
      vascularized soft tissue in addition to bone graft is desirable. The use of the
      corticoperiosteal vascularized bone graft from the medial femoral condyle is well
      described. There are only anecdotal reports about its use as an osteocutaneous
      flap. This article presents our results with the use of an osteocutaneous flap
      from the medial femoral condyle. Between 2004 and 2009, four patients were
      treated with supracondylar osteocutaneous flaps for bony nonunions (tibia, ankle,
      calcaneous) with concomitant soft tissue defects. The size of the osseous grafts
      ranged from 3 x 5 to 6 x 5 cm. The supplying cutaneous vessels were an unnamed
      perforator of the descending genicular artery (two cases) or the saphenous branch
      (two cases). The first three cases healed primarily. Bony union was achieved
      between 32 and 170 days. The follow-up of the fourth case was too short to
      achieve a bony union. There was no flap loss or surgery-related complications at
      the donor site. The transfer of free combined vascularized corticoperiosteal
      cutaneous flaps seems to be ideally suited for postradiation-induced fractures or
      chronic nonunions with poor chances of spontaneous healing and a concomitant
      small skin defect.

PMID- 20143300
TI  - A review of therapeutic nerve decompression for neuropathy in Hansen's disease
      with research suggestions.
AB  - Nerve decompression surgery for leprosy neuritis has a long history and large
      literature. New understanding of the high frequency of spontaneous recovery from
      nerve function impairment requires re-evaluation of the value of decompression in
      acute nerve dysfunction with strong evidence-based protocols. Several reports and
      theoretical considerations suggest research avenues that might offer hope for
      prevention of long-term complications and relief of impairment and disabilities.

PMID- 20143301
TI  - Pressure-specified sensory device versus electrodiagnostic testing in brachial
      plexus upper trunk injury.
AB  - Brachial plexus upper trunk injury is associated with winged scapula owing to the
      close anatomical course of the long thoracic nerve and upper trunk. Needle
      electromyography is a common diagnostic test for this injury; however, it does
      not detect injury in most patients with upper trunk damage. The pressure
      specified sensory device may be an alternative to needle electromyography. Thirty
      patients with winged scapula and upper trunk injury were evaluated with needle
      electromyography (EMG) and pressure-specified sensory device (PSSD) tests. EMG
      testing of the biceps muscle was compared with PSSD testing of the dorsal hand
      skin (C6 damage), and EMG testing of the deltoid and spinati muscles was compared
      with PSSD testing of the deltoid skin (C5 damage). PSSD pressure values were
      significantly higher on the affected arm. On the basis of published and
      calculated threshold values the PSSD was found to be significantly more sensitive
      than EMG. The PSSD tests consistently identified injuries that were not detected
      by needle EMG tests. These findings provide strong evidence that the PSSD is more
      effective than needle EMG in the detection of brachial plexus upper trunk injury.

PMID- 20143302
TI  - A new evaluation tool for monitoring devices and its application to evaluate the
      implantable Doppler probe.
AB  - Evaluation parameters for free flap monitoring devices are used inconsistently,
      leading to considerable confusion about the quality and applicability of these
      devices. A comparison of different systems and different clinical series is
      almost impossible. The ultimate questions that need to be answered are those
      regarding the efficiency and the effectiveness of the system. A new tool
      consisting of two simple parameters that sufficiently and comparably describe the
      quality of monitoring devices is developed. The flap failure reduction rate
      describes the percentage of saved flaps (effectiveness). The revision success
      rate describes the efficiency. Literature reevaluation shows inconsistent
      results, although all authors describe a positive experience. This shows the
      limited value of the classical parameters. Larger studies have flap failure
      reduction rates of 5 to 12% (5 to 12% of monitored flaps are saved). Revision
      success rates of 75 to 90% prove that the system is efficient enough in daily
      use. Reevaluation of the smaller reported series result in lower parameters,
      which shows that there is a significant learning curve for this device. The new
      parameters alleviate the confusion surrounding evaluation of monitoring systems
      by giving specific information about effectiveness and efficiency. The benefits
      of the implanted Doppler probe can now be clearly described. However, in several
      studies the benefit of the system is overrated.

PMID- 20143303
TI  - Which end is up? Terminology for terminolateral (end-to-side) nerve repair: a
      review.
AB  - By convention, we "come from" and "go to." A flap has a donor site and goes to a
      recipient site. A transplant comes from a donor and goes to a recipient. Neural
      regeneration proceeds from proximal to distal. It seems most appropriate then for
      a nerve repair description to follow this logical order. Therefore an "end-to
      side" repair would mean that the donor nerve, the nerve that is providing the
      axons with which to neurotize the recipient nerve, should be the nerve named
      first. An end-to-side repair would therefore require that the nerve whose end is
      sutured into the side of the recipient nerve be the nerve that is bringing the
      proximal axons to regenerate distally, for whatever that purpose may be, sensory
      or motor. A side-to-end repair would therefore require that the nerve whose side
      is sutured to the end of the recipient nerve be the nerve that is bringing the
      proximal axons to regenerate distally, for whatever that purpose may be, sensory
      or motor. The full descriptive phrase must include whether the intent is to
      reinnervate a skin target and is, therefore, a sensory repair, or to reinnervate
      a motor target. The names of both the donor and the recipient nerves must be
      specified. Illustrations of these logical possibilities are shown in this review
      of the modern history of "end-to-side" or "side-to-end" nerve coaptations.

PMID- 20143304
TI  - Does the number of choice sets matter? Results from a web survey applying a
      discrete choice experiment.
AB  - Optimising the design of discrete choice experiments (DCE) involves maximising
      not only the statistical efficiency, but also how the nature and complexity of
      the experiment itself affects model parameters and variance. The present paper
      contributes by investigating the impact of the number of DCE choice sets
      presented to each respondent on response rate, self-reported choice certainty,
      perceived choice difficulty, willingness-to-pay (WTP) estimates, and response
      variance. A sample of 1053 respondents was exposed to 5, 9 or 17 choice sets in a
      DCE eliciting preferences for dental services. Our results showed no differences
      in response rates and no systematic differences in the respondents' self-reported
      perception of the uncertainty of their DCE answers. There were some differences
      in WTP estimates suggesting that estimated preferences are to some extent context
      dependent, but no differences in standard deviations for WTP estimates or
      goodness-of-fit statistics. Respondents exposed to 17 choice sets had somewhat
      higher response variance compared to those exposed to 5 choice sets, indicating
      that cognitive burden may increase with the number of choice sets beyond a
      certain threshold. Overall, our results suggest that respondents are capable of
      managing multiple choice sets - in this case 17 choice sets - without problems.

PMID- 20143305
TI  - Therapeutic effect of transplanting beta(2)m(-)/Thy1(+) bone marrow-derived
      hepatocyte stem cells transduced with lentiviral-mediated HGF gene into CCl(4)
      injured rats.
AB  - BACKGROUND: beta(2)m(-)/Thy1(+) bone marrow-derived hepatocyte stem cells
      (BDHSCs) isolated from the bone marrow of cholestatic rats by magnetic bead cell
      sorting consistently express characteristics of both stem and liver cells. These
      stem cells may be good vehicles for gene transfer. Administration of exogenous
      hepatocyte growth factor (HGF) may be potentially useful for the treatment of
      liver fibrosis. Because lentiviral vectors integrate stably into the host-cell
      genome of nondividing and dividing cells, it may efficiently transfect beta(2)m(
      )/Thy1(+) BDHSCs in vitro and secrete high-level HGF consistently.
      Transplantation of beta(2)m(-)/Thy1(+) BDHSCs transduced with lentiviral vectors
      containing the HGF gene may reduce liver fibrosis in rats. METHODS: Lentiviral
      vectors expressing HGF were constructed and used to transduce beta(2)m(-)/Thy1(+)
      BDHSCs sorted from cholestatic rats in vitro. Transduction efficiency was
      evaluated and then these cells were transplanted into rats through the portal
      vein. Liver function as well as histological and immunohistochemical examinations
      were carried out to assess the therapeutic efficacy on liver fibrosis. RESULTS:
      We demonstrated that high-level exogenous HGF was detected in supernatants after
      beta(2)m(-)/Thy1(+) BDHSCs were transfected with lentiviral vectors expressing
      HGF. Transplantation of transduced beta(2)m(-)/Thy1(+) BDHSCs significantly
      enhanced liver function and attenuated liver fibrosis in vivo. CONCLUSIONS: The
      present study indicates that transplantation of beta(2)m(-)/Thy1(+) BDHSCs
      overexpressing the HGF gene may offer a novel approach for promoting liver
      function and reverse liver fibrosis.

PMID- 20143306
TI  - The feet of the measles virus polymerase bind the viral nucleocapsid protein at a
      single site.
AB  - Measles virus has a single-stranded RNA genome that is organized into a helical
      complex by the viral N protein. The resulting structure is termed the
      nucleocapsid and is traversed by the viral polymerase during RNA synthesis. The P
      protein, the noncatalytic subunit of the polymerase, provides the "legs and feet"
      that allow the polymerase to walk along its protein-RNA template. The polymerase
      feet are very simple three-helix bundles, only 50 amino acids in size.
      Previously, we have shown that these feet grasp the viral N protein during
      movement by attaching to a short sequence (amino acids 487-503) within the
      disordered and surface-exposed tail of N, causing it to fold into a helix. The
      result is a weak-affinity complex with a short lifetime, which would allow the
      polymerase to take rapid steps forward. The structure of the complex was
      determined using X-ray crystallography. This simple model of binding was
      challenged by a paper in this journal, claiming that a downstream sequence in the
      tail of N (amino acids 517-525) was also critical for the association. Its
      presence was reported to enhance the overall affinity of the polymerase feet for
      N by three orders of magnitude. We have, therefore, examined binding of the
      polymerase foot domain to amino acids 477-525 of N using quantitative biophysical
      techniques, and compared the results to our previous binding studies, performed
      using amino acids 477-505 of N. We find no evidence that the sequence downstream
      of amino acid 505 influences binding, validating the original single-site binding
      model.

PMID- 20143312
TI  - Psychometric properties of a Turkish version of the Difficulties in Emotion
      Regulation Scale.
AB  - This study aimed to examine the psychometric properties of the Difficulties in
      Emotion Regulation Scale (DERS; developed by Gratz & Roemer, 2004) in a Turkish
      sample. For this purpose, first, the factor structure of the scale was examined
      with a sample of 338 university students, and an identical factor structure with
      the original scale was obtained with the exclusion of a single item. Following
      the confirmation of the 6-factor structure of the scale with the current Turkish
      sample, the whole scale's and its six subscales' reliability coefficients were
      examined via internal consistency and test-retest reliability coefficients. These
      reliability analyses indicated satisfactory coefficients. As for the concurrent
      validity, the correlations of DERS and its subscales with measures of
      psychological distress were examined. This examination generally revealed strong
      correlations, although the awareness factor of DERS had relatively weaker
      correlations with the measures of psychological distress. Finally, concerning the
      criterion validity, all the measures of DERS could significantly differentiate
      the participants with "high psychological distress" from those with "low
      psychological distress"; however, for the awareness subscale the effect size was
      small. These findings were discussed in line with the relevant literature.

PMID- 20143313
TI  - Monocyte and neutrophil isolation and migration assays.
AB  - This unit describes methods for isolating mouse monocytes and neutrophils, as
      well as in vitro protocols for measuring cell migration and polarization. The
      method employed here for the isolation of naive phagocytes overcomes many of the
      difficulties previously encountered concerning phagocyte activation. Three in
      vitro protocols are provided for the analysis of cell migration, one requiring no
      specialized equipment, one requiring the modified Boyden chamber, and the other
      employing a flow chamber, which measures cell adhesion, rolling, and migration.
      Finally, a method is provided for imaging polarized cells by confocal microscopy.

PMID- 20143314
TI  - Experimental autoimmune encephalomyelitis in the mouse.
AB  - This unit details the materials and methods required for both active induction
      and adoptive transfer of experimental autoimmune encephalomyelitis (EAE) in the
      SJL mouse strain using intact proteins or peptides from the two major myelin
      proteins: proteolipid protein (PLP) and myelin basic protein (MBP). Detailed
      materials and methods required for the purification of both PLP and MBP are also
      described. A protocol for isolating CNS-infiltrating lymphocytes in EAE mice is
      included. Modifications of the specified protocols may be necessary for efficient
      induction of active or adoptive EAE in other mouse strains.

PMID- 20143315
TI  - Choosing and preparing antigen-presenting cells.
AB  - The first issue in selecting a system for antigen-presentation experiments is to
      define the appropriate type of antigen-presenting cell (APC) to study. For some
      experiments, crude preparations such as splenocytes or peripheral blood
      mononuclear cells (PBMCs) may suffice to provide APC function for stimulating T
      cells. This unit develops approaches for preparation of more defined APC
      populations, including dendritic cells (DCs), macrophages, and B lymphocytes, the
      three types of "professional" APC. Each of these cell types exists in different
      stages of differentiation, maturation, and activation, or in some cases different
      lineages. For example, dendritic cells may be divided into subsets, including
      myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). Each APC type has an important
      antigen-presentation function, although they contribute to different aspects of
      the immune response. Therefore, selection of an APC type for study must include
      consideration of the stage or aspect of immune response that is to be modeled in
      the experiment.

PMID- 20143316
TI  - Presenting exogenous antigen to T cells.
AB  - Antigen processing and presentation experiments can be done with a wide variety
      of antigen-presenting cells (APCs). Most experiments will use one of the
      "professional" APC types: dendritic cells (DCs), macrophages, and B lymphocytes.
      Other types of cells may be used for antigen presentation in some circumstances.
      Each type of professional APC has an important antigen-presentation function, but
      the different APC types contribute to different aspects of the immune response.
      Therefore, selection of an APC type for study must include consideration of the
      stage or aspect of immune response that is to be modeled in the experiment. An
      important technical distinction for some types of experiments is whether the APCs
      are adherent or nonadherent, since this dictates the procedures that must be used
      to wash the cells as the medium is changed.

PMID- 20143317
TI  - The MHC motif viewer: a visualization tool for MHC binding motifs.
AB  - In vertebrates, the onset of cellular immune reactions is controlled by
      presentation of peptides in complex with major histocompatibility complex (MHC)
      molecules to T cell receptors. In humans, MHCs are called human leukocyte
      antigens (HLAs). Different MHC molecules present different subsets of peptides,
      and knowledge of their binding specificities is important for understanding
      differences in the immune response between individuals. Algorithms predicting
      which peptides bind a given MHC molecule have recently been developed with high
      prediction accuracy. The utility of these algorithms is hampered by the lack of
      tools for browsing and comparing specificity of these molecules. We have
      developed a Web server, MHC Motif Viewer, which allows the display of the binding
      motif for MHC class I proteins for human, chimpanzee, rhesus monkey, mouse, and
      swine, as well as HLA-DR protein sequences. The binding motif for each MHC
      molecule is predicted using state-of-the-art, pan-specific peptide-MHC binding
      prediction methods, and is visualized as a sequence logo, in a format that allows
      for a comprehensive interpretation of binding motif anchor positions and amino
      acid preferences.

PMID- 20143318
TI  - Molecular dynamics study of interaction and substrate channeling between neuron
      specific enolase and B-type phosphoglycerate mutase.
AB  - Phosphoglycerate mutase (PGM) and enolase are consecutive enzymes in the
      glycolytic pathway. We used molecular dynamics simulation to examine the
      interaction of human B-type PGM (dPGM-B) and neuron-specific enolase (NSE).
      Specifically, we studied the interactions of 31 orientations of these enzymes by
      means of the effective energy function implicit solvation method. Interactions
      between active regions of the enzymes occurred preferentially, although the
      strongest interactions appeared to be between the back side of NSE and the active
      regions of dPGM-B. Cleavage of 2PG from dPGM-B was investigated, and the Ser(14)
      Leu(30) loop of dPGM-B is suggested as a cleavage site and, likely, another
      entrance site of a ligand. Substrate channeling between the enzymes was observed
      when NSE with its active regions Leu(11)-Asn(16), Arg(49)-Lys(59), and Gly(155)
      Ala(158) covered the Ser(14)-Leu(30) loop of dPGM-B. Analyses of the results make
      us believe that the channeling between PGM and enolase "benefits" from weak
      interaction. The probability of formation of channeling favorable complex is
      estimated to be up to 5%, while functional interaction between NSE and dPGM-B
      might be as high as 20%. NSE and dPGM-B functional interaction seems not to be
      isotype specific.

PMID- 20143319
TI  - Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals
      potent discriminatory classifiers of pancreatic cancer.
AB  - Poor outcome of pancreatic cancer necessitates development of an early diagnostic
      method to reduce mortality. No reliable early diagnostic test for pancreatic
      cancer detection has been developed and validated to date. In the current study,
      metabolic profiling of plasma samples from selected cancer patients and
      noncancerous controls was performed to seek novel metabolic biomarkers of
      pancreatic cancer. A comprehensive mass spectrometry based analytical platform
      established at the Metabolomics Core of the UC Davis Genome Center allowed
      detection of multiple compounds previously unreported in plasma from pancreatic
      cancer patients. It was found that selective amino acids, bile acids, and polar
      lipids were detected with increased or decreased levels in pancreatic cancer
      samples compared to controls. These findings on blood plasma levels of the
      relevant metabolites might be very useful clinical parameters for early diagnosis
      of pancreatic cancer.

PMID- 20143320
TI  - Fine structure of the branchial epithelium in the teleost Oreochromis niloticus.
AB  - We have studied the gill epithelium of Oreochromis niloticus using transmission
      electron microscopy with the particular interested relationship between cell
      morphology and osmotic, immunoregulatory, or other non-regulatory functions of
      the gill. Pavement cells covered the filament epithelium and lamellae of gills,
      with filament pavement cells showing distinct features from lamellar pavement
      cells. The superficial layer of the filament epithelium was formed by
      osmoregulatory elements, the columnar mitochondria-rich, mucous and support
      cells, as well as by their precursors. Light mitochondria-rich cells were located
      next to lamellae. They exhibited an apical crypt with microvilli and horizontal
      small dense rod-like vesicles, sealed by tight junctions to pavement cells. Dark
      mitochondria-rich cells had long dense rod-like vesicles and a small apical
      opening sealed by tight junctions to pavement cells. The deep layer of the
      filament epithelium was formed by a network of undifferentiated cells, containing
      neuroepithelial and myoepithelial cells, macrophage and eosinophil-like cells and
      their precursors, as well as precursors of mucous cells. The lateral-basal
      surface was coated by myoepithelial cells and a basal lamina. The lamellar blood
      lacunae was lined by pillar cells and surrounded by a basal lamina and pericytes.
      The data presented here support the existence of two distinct types of pavement
      cells, mitochondria-rich cells, and mitochondria-rich cells precursors, a
      structural role for support cells, a common origin for pavement cells and support
      cells, a paracrine function for neuroepithelial cells in the superficial layer,
      and the control of the lamellar capillary base by endocrine and contractile
      cells. Data further suggest that the filament superficial layer is involved in
      gill osmoregulation, that may interact, through pale mitochondria-rich cells,
      with the deep layer and lamellae, whereas the deep layer, through immune and
      neuroendocrine systems, acts in the regeneration and defense of the tissue.

PMID- 20143321
TI  - Bulimia nervosa with history of anorexia nervosa: could the clinical subtype of
      anorexia have implications for clinical status and treatment response?
AB  - OBJECTIVE: To investigate whether the subtype of anorexia nervosa (AN) could
      influence the bulimic syndrome and treatment response in bulimia nervosa (BN)
      patients with a history of AN (BN/AN+). METHOD: Seventy female BN patients were
      assessed for eating disorder, psychopathology and personality, and treated for 6
      months. RESULTS: BN/AN+ patients retained some traits of their past condition:
      lower body weight, higher perfectionism, and higher reward dependence. They also
      had more severe symptoms, longer evolution time, and worse response to treatment.
      A history of restricting AN was associated to higher age, longer evolution time,
      higher impulsivity, and greater tendency to use diet pills and diuretics. A
      history of binge-purging AN was associated to more severe vomiting, lower body
      dissatisfaction and less depressive symptoms, as well as better outcome.
      DISCUSSION: The influence of the AN subtype in BN/AN+ patients is worthy of
      further study as it might have clinical implications.

PMID- 20143322
TI  - Comparison of methods for identifying and assessing obese patients with binge
      eating disorder in primary care settings.
AB  - OBJECTIVE: Given the prevalence and health significance of binge eating disorder
      (BED) it is important to determine if time-efficient self-reports can adequately
      assess BED and its features in primary care settings. We compared the Eating
      Disorder Examination-Questionnaire (EDE-Q) and Questionnaire for Eating and
      Weight Patterns-Revised (QEWP-R), administered to obese patients with BED in
      primary care setting to the Eating Disorder Examination (EDE) interview. METHOD:
      Sixty-six participants completed the questionnaires and were interviewed.
      RESULTS: The EDE interview was significantly correlated with the EDE-Q (binge
      eating, four subscales, and global score) and the QEWP-R (binge eating, distress,
      and body image). The EDE-Q yielded significantly lower estimates of binge eating
      and significantly higher scores on the EDE subscales. The QEWP-R yielded
      significantly higher scores on the behavioral indicators and distress about binge
      eating and body image variables. DISCUSSION: These findings suggest that these
      two self-report measures have potential utility for identifying BED in obese
      patients in primary care.

PMID- 20143324
TI  - iHEA student competition 'Young Researchers in Health Economics'.

PMID- 20143323
TI  - Life beyond the eating disorder: education, relationships, and reproduction.
AB  - OBJECTIVE: We investigated the sociodemographic characteristics in women with and
      without lifetime eating disorders. METHOD: Participants were from a multisite
      international study of eating disorders (N = 2,096). Education level,
      relationship status, and reproductive status were examined across eating disorder
      subtypes and compared with a healthy control group. RESULTS: Overall, women with
      eating disorders were less educated than controls, and duration of illness and
      age of onset were associated with educational attainment. Menstrual status was
      associated with both relationship and reproductive status, but eating disorder
      subtypes did not differ significantly from each other or from healthy controls on
      these dimensions. DISCUSSION: Differences in educational attainment,
      relationships, and reproduction do exist in individuals with eating disorders and
      are differentially associated with various eating disorder symptoms and
      characteristics. These data could assist in educating patients and family members
      about long-term consequences of eating disorders.

PMID- 20143325
TI  - The role of socioeconomic status in adjustment after ductal carcinoma in situ.
AB  - BACKGROUND: A large body of literature suggests that socioeconomic status (SES)
      is positively associated with mental and physical health. However, little
      research has examined the impact of SES on psychological adjustment after a major
      stressor. The current study examined whether SES (education and financial status)
      was associated with distress (anxiety and depression) in women diagnosed with
      ductal carcinoma in situ (DCIS). This study also explored whether social support
      explained the association between SES and distress and whether social support
      buffered the impact of low SES on distress. METHODS: A total of 487 women with
      newly diagnosed DCIS were enrolled in the study. Participants completed questions
      about sociodemographic, psychosocial, and clinical characteristics at the time of
      enrollment and 9 months after their diagnosis. RESULTS: Financial status was
      inversely associated with anxiety and depression at the 9-month follow-up.
      Financial status also predicted change in anxiety and depression. Women with high
      financial status reported a decline in anxiety and depression during the study
      period, whereas women with medium or low financial status reported an increase in
      anxiety and depression. In addition, the probability of exceeding the screening
      threshold suggestive of clinical depression increased with decreasing financial
      status. Education was not associated with anxiety or depression. The presence of
      social support did not explain the association between financial status and
      change in distress. Social support did not buffer the effect of low SES on
      anxiety and depression. CONCLUSIONS: Women with medium or low SES were vulnerable
      to escalating anxiety and depression after a DCIS diagnosis.

PMID- 20143326
TI  - Independent and dependent contributions of advanced maternal and paternal ages to
      autism risk.
AB  - Reports on autism and parental age have yielded conflicting results on whether
      mothers, fathers, or both, contribute to increased risk. We analyzed restricted
      strata of parental age in a 10-year California birth cohort to determine the
      independent or dependent effect from each parent. Autism cases from California
      Department of Developmental Services records were linked to State birth files
      (1990-1999). Only singleton births with complete data on parental age and
      education were included (n=4,947,935, cases=12,159). In multivariate logistic
      regression models, advancing maternal age increased risk for autism monotonically
      regardless of the paternal age. Compared with mothers 25-29 years of age, the
      adjusted odds ratio (aOR) for mothers 40+ years was 1.51 (95% CI: 1.35-1.70), or
      compared with mothers <25 years of age, aOR=1.77 (95% CI, 1.56-2.00). In
      contrast, autism risk was associated with advancing paternal age primarily among
      mothers <30: aOR=1.59 (95% CI, 1.37-1.85) comparing fathers 40+ vs. 25-29 years
      of age. However, among mothers >30, the aOR was 1.13 (95% CI, 1.01-1.27) for
      fathers 40+ vs. 25-29 years of age, almost identical to the aOR for fathers <25
      years. Based on the first examination of heterogeneity in parental age effects,
      it appears that women's risk for delivering a child who develops autism increases
      throughout their reproductive years whereas father's age confers increased risk
      for autism when mothers are <30, but has little effect when mothers are past age
      30. We also calculated that the recent trend towards delayed childbearing
      contributed approximately a 4.6% increase in autism diagnoses in California over
      the decade.

PMID- 20143327
TI  - The effect of changes in Medicare reimbursement on the practice of office and
      hospital-based endoscopic surgery for bladder cancer.
AB  - BACKGROUND: Procedures performed in the office offer potential cost savings.
      Recent analyses suggest, however, that a fee-for-service system may incentivize
      subscale operations and, thus, contribute to excessive spending. The authors of
      this report sought to characterize changes in the practice of office-based and
      hospital-based endoscopic bladder surgery after 2005 increases in Medicare
      reimbursement. METHODS: All office and hospital-based endoscopic surgeries that
      were performed in a faculty practice from 2002 through 2007 were identified using
      billing codes for procedures, diagnoses, and procedure locations and then
      analyzed using the chi-square test and logistic regression. Costs were estimated
      based on published Medicare reimbursements for office and hospital-based
      surgeries. RESULTS: In total, 1341 endoscopic bladder surgeries were performed,
      including 764 in the office and 577 in the hospital. After 2005, the odds ratio
      (OR) for office surgery occurring among all cystoscopies and for surgery
      occurring in the office versus the hospital was 2.01 (95% confidence interval
      [CI], 1.71-2.37) and 2.29 (95% CI, 1.83-2.87), respectively. Among all treated
      lesions that were associated with a diagnosis of bladder cancer and nonbladder
      cancer, the OR for a procedure occurring in the office versus the hospital was
      1.36 (95% CI, 1.07-1.73) and 1.99 (95% CI, 1.52-2.60), respectively. The
      likelihood of repeat surgery on the same lesion increased after 2005 (OR, 2.86;
      95% CI, 1.46-5.62), and the likelihood of an office surgery leading to a bladder
      cancer diagnosis at the next visit declined (OR, 0.29; 95% CI, 0.16-0.51). The
      overall estimated expenditure increased by 50%. CONCLUSIONS: After 2005, more
      bladder lesions were identified and treated in the office. In a single group
      practice, office treatment of bladder cancer did not fully explain this new
      practice pattern, suggesting a lowered threshold for office intervention.

PMID- 20143328
TI  - Predictors of HAV/HBV vaccination completion among methadone maintenance clients.
AB  - This randomized, controlled study (N = 256) was conducted to compare three
      interventions designed to promote hepatitis A virus (HAV) and hepatitis B virus
      (HBV) vaccination completion among clients undergoing methadone maintenance (MM)
      treatment. Participants were recruited from five MM treatment sites in Southern
      California and randomized into three groups: Motivational Interviewing-Single (MI
      Single), Motivational Interviewing-Group (MI-Group); and Nurse-Led Hepatitis
      Health Promotion (HHP). All were offered the three-series HAV/HBV vaccine. A
      total of 148 participants completed the vaccine. Groups did not differ in rate of
      vaccination completion (73.6%, HHP group, vs. 65% and 69% for the MI-Single and
      MI-Group, respectively). The equivalence of findings across groups suggests the
      value of including nurses with a comprehensive health focus in promoting
      vaccination completion.

PMID- 20143329
TI  - Transcriptome study for early hematopoiesis--achievement, challenge and new
      opportunity.
AB  - Hematopoietic stem progenitor cells are the source for the entire hematopoietic
      system. Studying gene expression in hematopoietic stem progenitor cells will
      provide information to understand the genetic programs controlling early
      hematopoiesis, and to identify the gene targets to interfere hematopoietic
      disorders. Extensive efforts using cell biology, molecular biology, and genomics
      approaches have generated rich knowledge for the genes and functional pathways
      involving in early hematopoiesis. Challenges remain, however, including the
      rarity of the hematopoietic stem progenitor cells that set physical limitation
      for the study, the difficulty for reaching comprehensive transcriptome detection
      under the conventional genomics technologies, and the difficulty for using
      conventional biological methods to identify the key genes among large number of
      expressed genes controlling stem cell self-renewal and differentiation. The newly
      developed single-cell transcriptome method and the next-generation DNA sequencing
      technology provide new opportunities for transcriptome study for early
      hematopoietic. Using systems biology approach may reveal the insight of the
      genetic mechanisms controlling early hematopoiesis.

PMID- 20143331
TI  - Transdifferentiation potentiality of human Wharton's jelly stem cells towards
      vascular endothelial cells.
AB  - Human Wharton's jelly stem cells (HWJSC) emerged as a potential source of viable
      cells for use in tissue engineering. In this work, we have analyzed the
      transdifferentiation capabilities of HWJSC towards transdifferentiated
      endothelial-like cells (Tr-ELC) in order to establish the potential usefulness of
      these cells in vascular tissue engineering. Our results show that Tr-ELC became
      more polygonal and less proliferative than HWJSC, resembling the structure and
      proliferation rate of the endothelial cells. In addition, the markers of
      mesenchymal undifferentiation CD9, E-cad, PODXL, and SSEA-4 are downregulated in
      Tr-ELC, suggesting that these cells can be in the process of adult
      differentiation. Besides, RT-PCR and microarray analyses revealed that some genes
      with a role in defining the endothelial phenotype and structure are upregulated
      (VEGF-R1, EDF1, AAMP, CD31, CD34, CDH5, and ICAM2) or downregulated (VEGF) in Tr
      ELC, although a number of genes related to relevant endothelial cell functions
      (CD36, ECE2, VWF, THBD, PGI2, ECE1, and ACE) did not change or were only
      partially induced. All this implies that HWJSC are able to efficiently
      transdifferentiate towards Tr-ELC at the phenotypical level following a
      hierarchical pattern of gene activation, with an earlier induction of
      morphological and phenotypical genes.

PMID- 20143330
TI  - BMP-3 promotes mesenchymal stem cell proliferation through the TGF-beta/activin
      signaling pathway.
AB  - Adipogenesis plays a key role in the pathogenesis of obesity. It begins with the
      commitment of mesenchymal stem cells (MSCs) to the adipocyte lineage, followed by
      terminal differentiation of preadipocytes to mature adipocytes. A critical, but
      poorly understood, component of adipogenesis involves proliferation of MSCs and
      preadipocytes. The present study was undertaken to examine the hypothesis that
      bone morphogenetic protein-3 (BMP-3) promotes adipogenesis using C3H10T1/2 MSCs
      and 3T3-L1 preadipocytes as in vitro model systems. We demonstrated that although
      it did not promote the commitment of MSCs to the adipocyte lineage or the
      differentiation of preadipocytes to adipocytes, BMP-3-stimulated proliferation by
      threefold in both cell types. Owing to a lack of information on MSC
      proliferation, we then delineated the molecular mechanisms underlying BMP-3
      stimulated MSC proliferation. We showed that BMP-3 activated the transforming
      growth factor-beta (TGF-beta)/activin but not ERK1/2, p38 MAPK, or JNK signaling
      pathways in C3H10T1/2 cells. Furthermore, the TGF-beta/activin receptor kinase
      inhibitor SB-431542 blocked BMP-3-stimulated proliferation. Importantly, siRNA
      mediated knockdown of the key TGF-beta/activin signaling pathway components,
      ActRIIB, ALK4, or Smad2, abrogated the mitogenic effects of BMP-3 on MSCs.
      Together, these results demonstrate that BMP-3 stimulates MSC proliferation via
      the TGF-beta/activin signaling pathway, thus revealing a novel role for this
      divergent and poorly understood member of the TGF-beta superfamily in regulating
      MSC proliferation.

PMID- 20143332
TI  - Significance and outcome of left heart hypoplasia in fetal congenital
      diaphragmatic hernia.
AB  - OBJECTIVE: In patients with a left-sided congenital diaphragmatic hernia (CDH),
      the left ventricle (LV) is often compressed and smaller than normal. The
      objective of this study was to investigate whether small left heart dimensions
      prenatally normalize after birth in patients with CDH, or whether prenatal
      indices of left heart size and flow predict postnatal outcome. METHODS: Clinical
      and echocardiographic data were reviewed for patients diagnosed with left-sided
      CDH prenatally. Cardiac dimensions and flows were compared with normative data.
      Among liveborn patients, pre- and postnatal Z-scores of left heart structures
      were compared, and associations between prenatal indices and outcome were
      assessed. RESULTS: Of 125 patients diagnosed prenatally with CDH, 111 had a left
      sided defect. Of these, 85 were liveborn, including 20 with congenital heart
      disease. Gestational age-adjusted dimensions of fetal left heart structures,
      including aortic valve diameter, mitral valve (MV) diameter, LV long-axis, LV
      short-axis and LV volume, were all smaller than normal (P < 0.001). On average,
      the LV contributed 33 +/- 8% of combined ventricular output, lower than the
      normal 40-50%. Z-scores of left heart structures increased from the prenatal
      echocardiogram to the postnatal study, with average changes ranging from 0.56 +/-
      1.68 (aortic valve) to 1.39 +/- 1.85 (LV volume). Among liveborn patients, there
      was no association between prenatal left heart Z-scores and postnatal survival.
      CONCLUSIONS: Hypoplasia of and reduced flow through the left heart are common
      among fetuses with CDH. After birth and CDH repair, left heart dimensions
      generally normalize, with adequate size to support a biventricular circulation,
      even when there is very low flow through the left heart in mid- and late
      gestation.

PMID- 20143333
TI  - Both superficial and deep zone articular chondrocyte subpopulations exhibit the
      Crabtree effect but have different basal oxygen consumption rates.
AB  - In the absence of in vivo measurements, the oxygen concentration within articular
      cartilage is calculated from the balance between cellular oxygen consumption and
      mass transfer. Current estimates of the oxygen tension within articular cartilage
      are based on oxygen consumption data from full-depth tissue samples. However,
      superficial and deep cell subpopulations of articular cartilage express intrinsic
      metabolic differences. We test the hypothesis that the subpopulations differ with
      respect to their intrinsic oxygen consumption rate. Chondrocytes from the full
      cartilage thickness demonstrate enhanced oxygen consumption when deprived of
      glucose, consistent with the Crabtree phenomena. Chondrocyte subpopulations
      differ in the prevailing availability of oxygen and glucose, which decrease with
      distance from the cartilage-synovial fluid interface. Thus, we tested the
      hypothesis that the oxygen consumption of each subpopulation is modulated by
      nutrient availability, by examining the expression of the Crabtree effect. The
      deep cells had a greater oxygen consumption than the superficial cells (V(max) of
      6.6 compared to 3.2 fmol/cell/h), consistent with our observations of
      mitochondrial volume (mean values 52.0 vs. 36.4 microm(3)/cell). Both populations
      expressed the Crabtree phenomena, with oxygen consumption increasing
      approximately 2.5-fold in response to glycolytic inhibition by glucose
      deprivation or 2-deoxyglucose. Over 90% of this increase was oligomycin-sensitive
      and thus accounted for by oxidative phosphorylation. The data contributes towards
      our understanding of chondrocyte energy metabolism and provides information
      valuable for the accurate calculation of the oxygen concentration that the cells
      experience in vivo. The work has further application to the optimisation of
      bioreactor design and engineered tissues.

PMID- 20143334
TI  - Profilin-1 overexpression inhibits proliferation of MDA-MB-231 breast cancer
      cells partly through p27kip1 upregulation.
AB  - Profilin-1 (Pfn1), a ubiquitously expressed actin-binding protein, has gained
      interest in epithelial-derived cancer because of its downregulation in expression
      in various adenocarcinoma. Pfn1 overexpression impairs tumorigenic ability of
      human breast cancer xenografts thus suggesting that Pfn1 could be a tumor
      suppressor protein. The objective of the present study was to determine how Pfn1
      overexpression affects cell-cycle progression of breast cancer cells. We show
      that Pfn1 overexpression in MDA-MB-231 breast cancer cells causes cell-cycle
      arrest in G1 phase and dramatically reduced proliferation in culture. Pfn1
      overexpression results in increased protein stability of p27(kip1) (p27-a major
      cyclin-dependent kinase inhibitor) and marked elevation in the overall cellular
      level of p27. Proliferation defect of Pfn1 overexpressers can be partly rescued
      by silencing p27 expression thus suggesting a critical role of p27 in Pfn1
      induced growth inhibition of MDA-MB-231 cells. Finally, Pfn1 overexpression was
      found to sensitize MDA-MB-231 cells to apoptosis in response to cytotoxic
      stimulus thus suggesting for the first time that survival of breast cancer cells
      can also be negatively influenced by Pfn1 upregulation. These findings may
      provide novel insights underlying Pfn1's tumor-suppressive action.

PMID- 20143335
TI  - Non-genomic rapid inhibition of Na+/H+-exchange 1 and apoptotic immunosuppression
      in human T cells by glucocorticoids.
AB  - Glucocorticoids (GCs) have been employed as immunosuppressive agents for many
      years. However, it is still unclear how GCs instantly uncouple T cells from acute
      stressful inflammatory. In terms of time scale, the genomic activity of the
      classic GC receptor cannot fulfill this role under crisis; but a rapid non
      genomic response can. In a previous study, intracellular acidification was found
      to be due to a rapid non-genomic inhibition of Na(+)/H(+)-exchange 1 (NHE1) and
      this event led to the immunosuppression of T cell proliferation by progesterone.
      The aim of this study was to examine whether there is a rapid acidification
      response caused by an inhibition of NHE1 activity and to explore the differential
      non-genomic effect on immunosuppression of hydrocortisone and dexamethasone. The
      IC(50) values for NHE1-dependent pH(i) recovery by hydrocortisone and
      dexamethasone are 250 and 1 nM, respectively. Co-stimulation of GCs with
      phytohemagglutinin (PHA) is able to inhibit PHA-induced IL-2 secretion, IL-4
      secretion, and T-cell proliferation. Furthermore, apoptosis in PHA-activated T
      cells is not induced by hydrocortisone but by dexamethasone. The mechanism of
      immunosuppression on proliferation by dexamethasone was found to be different of
      hydrocortisone and seems to involve cytotoxicity against T cells. Moreover,
      apoptosis induced by dexamethasone and impermeable dexamethasone-bovine serum
      albumin suggests that the apoptotic immunosuppression occurs through both the
      plasma membrane and cytoplasmic sites. The rapid inhibitory responses triggered
      by GCs would seem to release T cells instantly when an acute stress-related
      response is needed. Nonetheless, the apoptotic immunosuppression by dexamethasone
      is attributable to its severe cytotoxicity.

PMID- 20143336
TI  - Downregulation of hepatic stellate cell activation by retinol and palmitate
      mediated by adipose differentiation-related protein (ADRP).
AB  - Hepatic stellate cells (HSCs) store retinoids and triacylglycerols in cytoplasmic
      lipid droplets. Two prominent features of HSC activation in liver fibrosis are
      loss of lipid droplets along with increase of alpha-smooth muscle actin (alpha
      SMA), but the link between these responses and HSC activation remains elusive. In
      non-adipose cells, adipose differentiation-related protein (ADRP) coats lipid
      droplets and regulates their formation and lipolysis; however its function in
      HSCs is unknown. Here, we observed, in human liver sections or primary HSC
      culture, ADRP localization to lipid droplets of HSCs, and reduced staining
      coincident with loss of lipid droplets in liver fibrosis and in culture-activated
      HSCs, consistent with HSC activation. In the LX-2 human immortalized HSCs, with
      scant lipid droplets and features of activated HSCs, we found that the
      upregulation of ADRP mRNA by palmitate is potentiated by retinol, accompanied by
      increased ADRP protein, generation of retinyl palmitate, and lipid droplet
      formation. ADRP induction also led to decreased expression of alpha-SMA mRNA and
      its protein, while ADRP knockdown with small interfering RNA (siRNA) normalized
      alpha-SMA expression. Furthermore, ADRP induction by retinol and palmitate
      resulted in decreased expression of collagen I and matrix metalloproteinase-2
      mRNA, fibrogenic genes associated with activated HSCs, while increasing matrix
      metalloproteinase-1 mRNA; ADRP knockdown with siRNA reversed these changes.
      Tissue inhibitor of metalloproteinase-1 was not affected. Thus, ADRP upregulation
      mediated by retinol and palmitate promotes downregulation of HSC activation and
      is functionally linked to the expression of fibrogenic genes.

PMID- 20143338
TI  - Compartmentalization of EGFR in cellular membranes: role of membrane rafts.
AB  - There is now abundant evidence that the intracellular concentration of the EGFR
      and many other receptors for peptide hormones and growth factors is important for
      the temporal and spatial regulation of cell signaling. Spatial control is
      achieved by the selective compartmentalization of signaling components into
      endosomes. However further control may be effected by sequestration into sub
      domains within a given organelle such as membrane rafts which are dynamic, nano
      scale structures rich in cholesterol and sphingolipids. Current data suggest the
      presence of EGFRs in non-caveolae membrane rafts. High doses of EGF seem to
      promote the sorting of EGFR to late endosomes through a raft/cholesterol
      dependant mechanism, implicating them in EGFR degradation. However our work and
      that of others has led us to propose a model in which membrane rafts in late
      endosomes sequester highly active EGFR leading to the recruitment and activation
      of MAPK in this compartment.

PMID- 20143337
TI  - Competitiveness for the niche and mutual dependence of the germline and somatic
      stem cells in the Drosophila testis are regulated by the JAK/STAT signaling.
AB  - In many tissues, two or more types of stem cells share a niche, and how the stem
      cells coordinate their self-renewal and differentiation is poorly understood. In
      the Drosophila testis, germ line stem cells (GSCs) and somatic cyst progenitor
      cells (CPCs) contact each other and share a niche (the hub). The hub expresses a
      growth factor unpaired (Upd) that activates the Janus kinase/signal transducer
      and activator of transcription (JAK/STAT) pathway in GSCs to regulate the stem
      cell self-renewal. Here, we demonstrate that the JAK/STAT signaling also
      regulates CPCs self-renewal. We also show that a negative regulator, the
      suppressor of cytokine signaling 36E (SOCS36E), suppresses JAK/STAT signaling in
      somatic cells, preventing them from out-competing the GSCs. Furthermore, through
      selectively manipulating the JAK/STAT signaling level in either CPCs or GSCs, we
      demonstrate that the somatic JAK/STAT signaling is essential for self-renewal and
      maintenance of both CPCs and GSCs. These data suggest that a single JAK/STAT
      signal from the niche orchestrate the competitive and dependent co-existence of
      GSCs and CPCs in the Drosophila testis niche.

PMID- 20143339
TI  - Factors associated with psychoactive drug initiation in a sample of workers in
      France: results of the VISAT cohort study.
AB  - PURPOSE: To identify which psychosocial factors at work are associated with the
      initiation of psychoactive drug use in a cohort of healthy French workers.
      METHOD: This study used data collected from the VISAT ('Vieillissement, Sante,
      Travail') cohort which included workers aged 32, 42, 52 and 62 years in 1996 with
      follow-ups conducted over the following 5 years. Data were collected through
      interviews and five standardized questionnaires in annual occupational medical
      examinations in 1996, 1999 and 2001. We defined new consumers of psychoactive
      drugs according to their answers during the follow-ups and compared their
      psychosocial and working characteristics to non-consumers. A multivariate
      logistic regression analysis was performed to investigate factors related to a
      psychoactive drug initiation. RESULTS: Among 1533 subjects, 5.4% began consuming
      psychoactive drugs during the follow-up with a twofold rate for women than for
      men. Factors related to psychoactive drug initiation were different according to
      gender. In men, initiation was mainly found in participants who were separated,
      showed high emotional reaction scores and were members of the white-collar
      working class. We did not find any other occupational factors associated to
      psychoactive drug initiation in men. By contrast, among women, drug initiation
      was more frequent in participants who were 52 years old and over, and whose job
      control-reward level was lower. CONCLUSIONS: Psychoactive drug initiation
      concerned 5.4% of workers within the 5-year interval in this study. The pressure
      of psychosocial environment was more important in men, whereas age and work
      related psychosocial factors were the main factors associated with new
      consumption among women.

PMID- 20143340
TI  - Statistical resource needs to be increased in the European regulatory agencies.
AB  - The following viewpoint from PSI and EFSPI regarding the current level of
      statistical resource in the European regulatory agencies was first presented as a
      position paper to a meeting of the EU Heads of Agencies in July 2009, and was
      endorsed by EFPIA.

PMID- 20143341
TI  - The impact of period effects on dose level contrasts in alternating cross-over
      designs for first-time-in-human studies.
AB  - For first-time-in-human studies with small molecules alternating cross-over
      designs are often employed and at study end are analyzed using linear models. We
      discuss the impact of including a period effect in the model on the precision
      with which dose level contrasts can be estimated and quantify the bias of least
      squares estimators if a period effect is inherent in the data that is not
      accounted for in the model. We also propose two alternative designs that allow a
      more precise estimation of dose level contrasts compared with the standard design
      when period effects are included in the model.

PMID- 20143342
TI  - Subjective sleep quality in women experiencing intimate partner violence:
      contributions of situational, psychological, and physiological factors.
AB  - This study, guided by an adaptation of the theory of unpleasant symptoms,
      examined the complex relationships of childhood maltreatment, intimate partner
      violence (IPV), posttraumatic stress disorder (PTSD), depression, and physical
      health symptoms with global sleep quality and disruptive nighttime behaviors.
      Data were analyzed using covariance structure analysis. A convenience sample of
      157 women currently experiencing IPV was recruited from crisis shelters and
      community agencies. Findings provide empirical support that women concurrently
      experiencing PTSD, depression, and stress-related physical health symptoms
      demonstrated poor global sleep quality and frequent disruptive nighttime
      behaviors. Posttraumatic stress disorder and stress health symptoms functioned as
      mediators of childhood maltreatment and IPV effects on both global sleep quality
      and disruptive nighttime behaviors, but depression did not.

PMID- 20143343
TI  - Strategies for DNA interstrand crosslink repair: insights from worms, flies,
      frogs, and slime molds.
AB  - DNA interstrand crosslinks (ICLs) are complex lesions that covalently link both
      strands of the DNA double helix and impede essential cellular processes such as
      DNA replication and transcription. Recent studies suggest that multiple repair
      pathways are involved in their removal. Elegant genetic analysis has demonstrated
      that at least three distinct sets of pathways cooperate in the repair and/or
      bypass of ICLs in budding yeast. Although the mechanisms of ICL repair in mammals
      appear similar to those in yeast, important differences have been documented. In
      addition, mammalian crosslink repair requires other repair factors, such as the
      Fanconi anemia proteins, whose functions are poorly understood. Because many of
      these proteins are conserved in simpler metazoans, nonmammalian models have
      become attractive systems for studying the function(s) of key crosslink repair
      factors. This review discusses the contributions that various model organisms
      have made to the field of ICL repair. Specifically, it highlights how studies
      performed with C. elegans, Drosophila, Xenopus, and the social amoeba
      Dictyostelium serve to complement those from bacteria, yeast, and mammals.
      Together, these investigations have revealed that although the underlying themes
      of ICL repair are largely conserved, the complement of DNA repair proteins
      utilized and the ways in which each of the proteins is used can vary
      substantially between different organisms.

PMID- 20143344
TI  - DNA damages induced by trans, trans-2,4-decadienal (tt-DDE), a component of
      cooking oil fume, in human bronchial epithelial cells.
AB  - Epidemiological studies have demonstrated that cooking oil fumes (COF) are an
      environmental risk factor for the development of lung adenocarcinoma among
      nonsmoking females in Taiwan. Aside from polycyclic aromatic hydrocarbons,
      aldehydes, especially trans, trans-2,4-decadienal (tt-DDE) are found to be
      abundant in COF. Although there is indication that tt-DDE induces DNA damage, the
      precise role of tt-DDE in the induction of DNA damage in lung cells is still not
      clear. When we assessed DNA breaks with the Comet assay, we found that the DNA
      breaks induced by 1 muM tt-DDE in human bronchial epithelial cells (BEAS-2B)
      could be significantly reduced by antioxidants, suggesting that oxidative stress
      was involved. Indeed, when tt-DDE-treated cells were coincubated with
      endonuclease III/formamidopyrimidine-DNA glycosylase or with nuclear extract
      (NE), an enhancement of DNA breaks was observed at 1 hr after tt-DDE exposure.
      Furthermore, when NE was incubated with an antibody against 8-oxoguanine DNA
      glycosylase (anti-OGG1), a reduction in tt-DDE/NE-induced DNA breaks could be
      demonstrated. Since OGG1 is a specific repair enzyme for 8-oxo-deoxyguanosine (8
      oxo-dG), these findings indicated that 8-oxo-dG was involved. On the other hand,
      when NE was incubated with antibodies against nucleotide excision repair enzymes,
      there was a significant reduction in tt-DDE/NE-induced DNA breaks at 4 hr after
      tt-DDE treatment. These observations indicate that, in addition to early
      oxidative DNA damage, nonoxidative DNA damage such as bulky adduct formation, was
      also induced by tt-DDE. Our study further affirms that tt-DDE is genotoxic to
      human lung cells and can increase carcinogenic risk.

PMID- 20143345
TI  - Building a zoo of mice for genetic analyses: a comprehensive protocol for the
      rapid generation of BAC transgenic mice.
AB  - Transgenic mice are highly valuable tools for biological research as they allow
      cell type-specific expression of functionally instrumental genes. In this
      protocol, the generation of bacterial artificial chromosome (BAC) transgenic
      constructs is described. We give an overview of different transgenic inserts,
      such as fluorescent proteins (alone or in combination with Cre variants),
      diphtheria toxin receptor, lacZ, and light-activated ion channels. The most
      reliable and versatile approach to express these genes is by using BACs, which
      allow "highjacking" of the expression pattern of a gene without characterizing
      its transcriptional control elements. Here, we describe the necessary cloning
      techniques compared with conventional transgenesis. With the provided "toolbox"
      of already available transgene constructs, the generation of the BAC transgenes
      is made easy and rapid. We provide a comprehensive outline how to insert the
      different transgenes into a chosen BAC by either ET cloning or recombineering. We
      also describe in detail the methods to identify the correct insertion and the
      integrity of the final BAC construct, and finally, the preparation of the BAC DNA
      for oocyte injection is described.

PMID- 20143346
TI  - A transgenic Cre mouse line for the study of cortical and hippocampal
      development.
AB  - Wnt signaling regulates cortical and hippocampal development. In a previous study
      we found that a particular Wnt receptor, Frizzled9 (Fzd9), was selectively
      expressed in both the developing and adult hippocampus. Taking advantage of the
      specificity of this promoter, we generated a transgenic cre mouse line using the
      putative control elements of the Fzd9 gene. In the Fzd9-cre mice, Cre is mainly
      detected in the developing cortex and hippocampus and is confined to the CA
      fields and dentate gyrus in adults. Furthermore, by crossing the Fzd9-cre mouse
      with the ROSA26 reporter line, we examined the activity of Cre and found that it
      has very high recombination efficiency. Thus, this mouse line will likely prove
      to be a useful tool for studying cortical and hippocampal development via
      activation or inactivation of interesting genes.

PMID- 20143347
TI  - Polyploidy-associated genomic instability in Arabidopsis thaliana.
AB  - Formation of polyploid organisms by fertilization of unreduced gametes in meiotic
      mutants is believed to be a common phenomenon in species evolution. However, not
      well understood is how species in nature generally exist as haploid and diploid
      organisms in a long evolutionary time while polyploidization must have repeatedly
      occurred via meiotic mutations. Here, we show that the ploidy increased for two
      consecutive generations due to unreduced but viable gametes in the Arabidopsis
      cyclin a1;2-2 (also named tardy asynchronous meiosis-2) mutant, but the resultant
      octaploid plants produced progeny of either the same or reduced ploidy via
      genomic reductions during meiosis and pollen mitosis. Ploidy reductions through
      sexual reproduction were also observed in independently generated artificial
      octaploid and hexaploid Arabidopsis plants. These results demonstrate that
      octaploid is likely the maximal ploidy produced through sexual reproduction in
      Arabidopsis. The polyploidy-associated genomic instability may be a general
      phenomenon that constrains ploidy levels in species evolution.

PMID- 20143348
TI  - Transfer of quantum dots from pregnant mice to pups across the placental barrier.
AB  - Fluorescent quantum dots (QDs) have great potential for in vivo biomedical
      imaging and diagnostic applications. However, these nanoparticles are composed of
      heavy metals and are very small in diameter, and their possible toxicity must
      therefore be considered. As yet, no studies have reported the transfer of QDs
      between mother and fetus. The transfer of CdTe/CdS QDs of different sizes and
      dosages, and with different outer capping materials, from pregnant mice to
      fetuses is investigated. It is shown that QDs may be transferred from female mice
      to their fetuses across the placental barrier. Smaller QDs are more easily
      transferred than larger QDs and the number of QDs transferred increases with
      increasing dosage. Capping with an inorganic silica shell or organic polyethylene
      glycol reduces QD transfer but does not eliminate it. These results suggest that
      the clinical utility of QDs could be limited in pregnant women.

PMID- 20143350
TI  - Salivary gland extract from engorged Ixodes ricinus (Acari: Ixodidae) stimulates
      in vitro growth of Borrelia burgdorferi sensu lato.
AB  - In vitro effect of salivary gland extract from fed Ixodes ricinus, the competent
      vector of Lyme borreliosis in Europe, on the growth of Borrelia burgdorferi sensu
      lato (B. garinii, B. afzelii and B. burgdorferi sensu stricto) was examined in
      BSK-H medium. Motility rate, concentration of motile spirochetes and their
      morphology were estimated at intervals of 0, 2, 4, 6 and 8 days using darkfield
      microscopy. Salivary gland extract derived from I. ricinus stimulated markedly
      the growth of three genomic species of borreliae. The results confirm a
      substantial role of salivary glands in the mechanism of pathogen transmission to
      vertebrate host.

PMID- 20143349
TI  - Microcontact printing onto oxide-free silicon via highly reactive acid fluoride
      functionalized monolayers.
AB  - This work describes a new route for patterning organic monolayers on oxide-free
      silicon by microcontact printing (microCP) on a preformed, reactive, acid
      fluoride-terminated monolayer. This indirect printing approach is fast and easily
      preserves the oxide-free and well-defined monolayer-silicon interface, which is
      the most important property for potential applications in biosensing and
      molecular electronics. Water-contact-angle measurements, ellipsometry, attenuated
      total reflection infrared spectroscopy, and X-ray photoelectron spectroscopy
      (XPS) demonstrate the formation of the initial acid-fluoride-terminated
      monolayers without upside-down attachment. Subsequent printing for twenty seconds
      with an N-hexadecylamine-inked poly(dimethylsiloxane) stamp results in well
      defined 5-microm N-hexadecylamide dots, as evidenced by atomic force microscopy
      and scanning electron microscopy. Printing with a flat stamp allows investigation
      of the efficiency of amide formation by microCP and water-contact-angle
      measurements, ellipsometry, and XPS reveal the quantitative conversion of the
      acid fluoride groups to the corresponding amide within twenty seconds. The
      absence of silicon oxide, even after immersion in water for 16 h, demonstrates
      that the oxide-free monolayer-silicon interface is easily preserved by this
      patterning route. Finally, it is shown by fluorescence microscopy that complex
      biomolecules, like functionalized oligo-DNA, can also be immobilized on the oxide
      free silicon surface via microCP.

PMID- 20143351
TI  - Expression of hcp in freshwater Synechococcus spp., a gene encoding a
      hyperconserved protein in picocyanobacteria.
AB  - Marine picoplankton of the genus Synechococcus and Prochlorococcus spp. are
      widely studied members of the picocyanobacterial clade, composed of unicellular
      cyanobacteria that dominate pelagic regions of the ocean. Less studied are the
      related freshwater Synechococcus spp. that similarly dominate the euphotic zone
      of oligotrophic lakes. Previous work has shown that marine picocyanobacteria
      harbor a small gene, hcp, that encodes a 62 amino acid protein 100% conserved
      among all strains examined. The gene is restricted exclusively to the
      picocyanobacterial lineage. The current study reveals that hcp is also 100%
      conserved in four freshwater Synechococcus spp. strains isolated from the
      Laurentian Great Lakes, and that the gene constitutively expressed with genes
      encoding a ribosomal protein and two tRNA genes. The synteny of the hcp region is
      also conserved between the marine and freshwater strains. Last, the hcp gene and
      the organization of the surrounding genetic region has been retained in the
      reduced genome of a picocyanobacterial endosymbiont of the amoeba Paulinella sp.

PMID- 20143352
TI  - Oxidation of aliphatic, branched chain, and aromatic hydrocarbons by Nocardia
      cyriacigeorgica isolated from oil-polluted sand samples collected in the Saudi
      Arabian Desert.
AB  - A soil bacterium isolated from oil-polluted sand samples collected in the Saudi
      Arabian Desert has been determined as Nocardia cyriacigeorgica, which has a high
      capacity of degrading and utilizing a broad range of hydrocarbons. The metabolic
      pathways of three classes of hydrocarbons were elucidated by identifying
      metabolites in cell-free extracts analyzed by GC/MS and HPLC/UV-Vis in comparison
      with standard compounds. During tetradecane oxidation, tetradecanol;
      tetradecanoic acid; dodecanoic acid; decanoic acid could be found as metabolites,
      indicating a monoterminal degradation pathway of n -alkanes. The oxidation of
      pristane resulted in the presence of pristanoic acid; 2-methylglutaric acid; 4,8
      dimethylnonanoic acid; and 2,6-dimethylheptanoic acid, which give rise to a
      possible mono- and di-terminal oxidation. In case of sec -octylbenzene, eight
      metabolites were detected including 5-phenylhexanoic acid; 3-phenylbutyric acid;
      2-phenylpropionic acid; beta -methylcinnamic acid; acetophenone; beta -hydroxy
      acetophenone; 2,3-dihydroxy benzoic acid and succinic acid. From these
      intermediates a new degradation pathway for sec -octylbenzene was investigated.
      Our results indicate that N. cyriacigeorgica has the ability to degrade aliphatic
      and branched chain alkanes as well as alkylbenzene effectively and, therefore, N.
      cyriacigeorgica is probably a suitable bacterium for biodegradation of oil or
      petroleum products in contaminated soils.

PMID- 20143353
TI  - Practical procedures for genetic manipulation systems for medermycin-producing
      Streptomyces sp. AM-7161.
AB  - Streptomyces sp. AM-7161 is a producer of an aromatic polyketide medermycin with
      strong antibacterial and antitumor activity. It has been inefficient to perform
      genetic manipulations in this strain, which heavily hinders the genetic analysis
      of some interesting problems concerning tailoring modifications in medermycin
      biosynthesis. Here, condition optimizations of sporulation and mycelium growth of
      this strain as well as protoplast preparation and regeneration were conducted
      systematically. Based on these results, protoplast transformation system was
      established, and two types of foreign plasmids (integrative and auto-replicating)
      were efficiently introduced into this strain. Additionally, a conjugation system
      to mediate plasmid transfer between Escherichia coli and Streptomyces sp. AM-7161
      was also optimized and established. These results provide the practical
      procedures to perform more convenient genetic analysis of medermycin biosynthesis
      in this strain.

PMID- 20143354
TI  - Molecular diversity of peanut-nodulating rhizobia in soils of Argentina.
AB  - RSalpha sequencing is a valuable tool for identification of bacterial strains,
      and for evaluating the genetic structure of indigenous rhizobial populations. The
      purpose of this study was to evaluate, qualitatively, the presence or absence of
      RSalpha fragment in peanut-nodulating strains isolated from plants grown at four
      sites in central Argentina. RSalpha fragment was found in only three of 26
      indigenous strains, and in one of three inoculant strains analyzed. In contrast
      to results from studies of other symbiotic nitrogen-fixing bacteria, such as
      soybean-nodulating strains, no correlation was found between generation time and
      presence of RSalpha sequence. Phylogenetic analysis of the 16S rRNA gene sequence
      grouped peanut-nodulating strains into two clusters, Bradyrhizobium japonicum vs.
      B. elkanii, and showed divergence among strains positive for RSalpha sequence.
      Our results confirm the genetic diversity previously reported for various peanut
      nodulating rhizobial strains, and indicate that the RSalpha fragment is not
      applicable as a marker or tool for competition assays at the field or ecological
      level.

PMID- 20143355
TI  - Effect of salinity on denitrification under limited single carbon source by
      Marinobacter sp. isolated from marine sediment.
AB  - Marinobacter comprises Gram-negative, aerobic, motile, and rod-shaped bacteria
      within the gamma-subclass of the Proteobacteria and is known to be halophilic or
      halotolerant, heterotrophic neutrophile. Two strains classified as belonging to
      Marinobacter, named PAD-2 and SeT-1, were isolated from marine sediment. The most
      closely related species of PAD-2 and SeT-1 are M. alkaliphilus and M. guinea,
      respectively. The strain PAD-2 exhibited remarkably higher denitrification at
      concentrations of 0.5 to 1 M NaCl (3-6% w/w) than at other salinities (2 and 3 M
      NaCl, 12-18% w/w), and optimal denitrification was observed in media with 0.5 M
      NaCl. The effect of pH on denitrification by strain PAD-2 was also examined, and
      the optimum denitrification occurred at neutral pH rather than under alkaline
      conditions. Overall, strain PAD-2 appears to be a novel halotolerant species
      belonging to the genus Marinobacter that shares many characteristics, such as
      substrate utilization profile and optimum NaCl concentration for growth with M.
      alkaliphilus.

PMID- 20143356
TI  - Combinatorial assessment on dominance and informative diversity of PGPR from
      rhizosphere of Jatropha curcas L.
AB  - The extensive and enduring challenges in soil microbiology depend on the
      development of efficient methods to be acquainted with the types of microbes
      present in soil, and to determine the functional performance of the overall
      microbial groups in situ. This study aims to investigate the combined uses of
      species richness and diversity as well as to estimate the combinatorial effect of
      species richness and diversity in order to understand their role and distribution
      in their habitat. To achieve this objective a study was designed targeting the
      rhizosphere of Jatropha curcas L. which were planted in various soil conditions
      on five distinctive sites of Gujarat state (India). These sites were constantly
      monitored and studied for the species richness and evenness ("heterogeneity").
      The isolates were checked for their PGPR potentials like Phosphate
      solubilisation, Siderophore production, Indole acetic acid production, ACC
      deaminase production, HCN production, EPS production and Ammonia production. The
      results obtained were used to calculate richness, evenness and diversity indices.
      Results reveal the total heterogeneity in the site of fertile Jatropha
      rhizosphere (GS4) as well as sodic soil site (GS5) than other three sites.
      Absence of equitability under the selected and defined condition was also
      observed in GS4 and GS5 sites. The combinatorial estimates provide the
      information on their distribution and roles in the habitat. In particular, such
      an empirical relationship from a single rhizosphere of a distinctive species
      Jatropha is useful to test diversity predictions in natural sites, and further it
      can be applied to either by performing trials over larger spatial and temporal
      scales or by conducting correlational studies of biodiversity gradients.

PMID- 20143357
TI  - Chemoenzymatic synthesis of a glycolipid library and elucidation of the antigenic
      epitope for construction of a vaccine against Lyme disease.
AB  - Lyme disease (LD) is the most common tick-borne disease in Europe, North America,
      and Asia. The etiologic agents of LD are spirochetes of the group Borrelia
      burgdorferi sensu lato, which possess a lipid content of 25-30% of the dry
      weight. The major glycolipid cholesteryl 6-O-acyl-beta-D-galactopyranoside
      (ACGal), present in B. burgdorferi sensu stricto, B. afzelii, and B. garinii, is
      a specific and highly prevalent antigen frequently recognized by antibodies in
      late-stage LD. Here we report a convenient route for the chemical synthesis of
      ACGal by employing a combination of chemical synthesis steps with enzymatic
      transformations. This synthesized molecule was compared with bacterial extracts
      by immunoblots with patient sera, confirming the preserved antigenicity. Next, a
      glycolipid library derived from the native molecules with variations in the fatty
      acyl moiety and derivatives in which the cholesterol has been replaced was
      designed and synthesized. The chemical structures were confirmed by 1D and 2D NMR
      spectroscopy and mass spectrometry. The native and synthetic glycolipids were
      utilized in immunoblots to determine the epitope recognized by antibodies in
      patient sera. By this method we could demonstrate that galactose, cholesterol,
      and a fatty acid with a minimal chain length of four carbon atoms comprises the
      essential structure for recognition by antibodies. Finally, this finding allowed
      the synthesis of a functionalized ACGal with an omega-mercapto group at the fatty
      acid and a facile protection and deprotection strategy. This antigenic hapten can
      be conjugated to a carrier protein to effect immunization against Lyme disease.

PMID- 20143358
TI  - Mechanistic exploration of intramolecular aminodiene hydroamination/cyclisation
      mediated by constrained geometry organoactinide complexes: a DFT study.
AB  - The present computational mechanistic study explores comprehensively the
      organoactinide-mediated intramolecular hydroamination/cyclisation (IHC) of
      aminodienes by employing a reliable DFT method. All the steps of a plausible
      catalytic reaction course have been scrutinised for the IHC of (4E,6)
      heptadienylamine 1t by [(CGC)Th(NMe(2))(2)] precatalyst 2 (CGC=[Me(2)Si(eta(5)
      Me(4)C(5))(tBuN)](2-)). For each of the relevant elementary steps the most
      accessible pathway has been identified from a multitude of mechanistic
      possibilities. The operative mechanism involves rapid substrate
      association/dissociation equilibria for the 3t-S resting state and also for
      azacyclic intermediates 4a, 4s, easily accessible and reversible exocyclic ring
      closure, supposedly facile isomerisation of the azacycle's butenyl tether prior
      to turnover-limiting protonolysis. The following aspects are in support of this
      scenario: 1) the derived rate law is consistent with the experimentally obtained
      empirical rate law; 2) the accessed barrier for turnover-limiting protonolysis
      does agree remarkably well with observed performance data; 3) the ring-tether
      double-bond selectivity is consistently elucidated, which led to predict the
      product distribution correctly. This study provides a computationally
      substantiated rationale for observed activity and selectivity data. Steric
      demands at the CGC framework appear to be an efficient means for modulating both
      performance and ring-tether double-bond selectivity. The careful comparison of
      (CGC)4f-element and (CGC)5f-element catalysts revealed that aminodiene IHC
      mediated by organoactinides and organolanthanides proceeds through a similar
      mechanistic scenario. However, cyclisation and protonolysis steps, in particular,
      feature a markedly different reactivity pattern for the two catalyst classes,
      owing to enhanced bond covalency of early actinides when compared to lanthanides.

PMID- 20143359
TI  - Functionalization of organic molecules by transition-metal-catalyzed C(sp3)-H
      activation.
AB  - Transition-metal-catalyzed C-H activation has recently emerged as a powerful tool
      for the functionalization of organic molecules. While many efforts have focused
      on the functionalization of arenes and heteroarenes by this strategy in the past
      two decades, much less research has been devoted to the activation of non-acidic
      C-H bonds of alkyl groups. This Minireview highlights recent work in this area,
      with a particular emphasis on synthetically useful methods.

PMID- 20143360
TI  - Aggregation-controlled excimer emission from anthracene-containing polyamidoamine
      dendrimers.
AB  - Lower generations of polyamidoamine (PAMAM) dendrimers were peripherally modified
      with anthracene moieties, and excimer emission from anthracene chromophores was
      investigated in an acetonitrile-water mixture at acidic and basic pH values.
      Results from fluorescence spectroscopic experiments suggest that 1) the
      propensity of anthracene-modified PAMAM dendrimers to aggregate in acetonitrile
      is substantial in the presence of 15-20 vol % of water, and 2) aggregate
      formation in anthracene-modified PAMAM dendrimers leads to unique morphologies in
      the ground state, where the anthracene units are pre-arranged to form stable
      excimers upon photoexcitation. Three types of anthracene excimers are generated
      in the system, with face-to-face, angular, and T-shaped geometry. The formation
      of different types of anthracene excimers was confirmed by steady-state and time
      resolved fluorescence spectroscopic experiments. Experimental results further
      suggest that it is feasible to alter the type of excimer formed by anthracene
      units attached to the PAMAM dendrimers through altering the propensity for ground
      state aggregation. Most excitingly, increased pi conjugation in the molecular
      framework of anthracene-substituted PAMAM dendrimers leads to intense and
      exclusive excimer emission from anthracene at room temperature.

PMID- 20143361
TI  - Chelation versus binucleation: metal complex formation with the hexadentate all
      cis-N1,N2-bis(2,4,6-trihydroxy-3,5-diaminocyclohexyl)ethane-1,2-diamine.
AB  - The hexadentate ligand all-cis-N(1),N(2)-bis(2,4,6-trihydroxy-3,5
      diaminocyclohexyl)ethane-1,2-diamine (L(e)) was synthesized in five steps with an
      overall yield of 39% by using [Ni(taci)(2)]SO(4).4H(2)O as starting material
      (taci=1,3,5-triamino-1,3,5-trideoxy-cis-inositol). Crystal structures of
      [Na(0.5)(H(6)L(e))](BiCl(6))(2)Cl(0.5).4H(2)O (1), [Ni(L(e))]Cl(2).5H(2)O (2),
      [Cu(L(e))](ClO(4))(2).H(2)O (3), [Zn(L(e))]CO(3).7H(2)O (4),
      [Co(L(e))](ClO(4))(3) (5c), and [Ga(H(-2)L(e))]NO(3).2H(2)O (6) are reported. The
      Na complex 1 exhibited a chain structure with the Na(+) cations bonded to three
      hydroxy groups of one taci subunit of the fully protonated H(6)(L(e))(6+) ligand.
      In 2, 3, 4, and 5c, a mononuclear hexaamine coordination was found. In the Ga
      complex 6, a mononuclear hexadentate coordination was also observed, but the
      metal binding occurred through four amino groups and two alkoxo groups of the
      doubly deprotonated H(-2)(L(e))(2-). The steric strain within the molecular
      framework of various M(L(e)) isomers was analyzed by means of molecular mechanics
      calculations. The formation of complexes of L(e) with Mn(II), Cu(II), Zn(II), and
      Cd(II) was investigated in aqueous solution by using potentiometric and
      spectrophotometric titration experiments. Extended equilibrium systems comprising
      a large number of species were observed, such as [M(L(e))](2+), protonated
      complexes [MH(z)(L(e))](2+z) and oligonuclear aggregates. The pK(a) values of
      H(6)(L(e))(6+) (25 degrees C, mu=0.10 M) were found to be 2.99, 5.63, 6.72, 7.38,
      8.37, and 9.07, and the determined formation constants (log beta) of
      [M(L(e))](2+) were 6.13(3) (Mn(II)), 20.11(2) (Cu(II)), 13.60(2) (Zn(II)), and
      10.43(2) (Cd(II)). The redox potentials (vs. NHE) of the [M(L(e))](3+/2+) couples
      were elucidated for Co (-0.38 V) and Ni (+0.90 V) by cyclic voltammetry.

PMID- 20143362
TI  - Spermine-functionalized perylene bisimide dyes--highly fluorescent bola
      amphiphiles in water.
AB  - A series of four spermine-functionalized perylene bisimide dyes without linkers
      (1) and with linkers (2-4) between the chromophore and the polyamine was
      synthesized. Protonation of the spermine moieties resulted in the formation of
      highly water-soluble dyes with up to six positively charged ammonium ions. The
      aggregation behavior of these strongly fluorescent bola-amphiphiles was studied
      in pure water as solvent by UV/Vis and fluorescence spectroscopy, and an
      astonishingly high fluorescence quantum yield of up to Phi(fl)=0.90 was observed
      for PBI 1. Atomic force microscopy and transmission electron microscopy were
      applied for the visualization of the aggregates on surfaces. Molecular modeling
      studies were performed by force-field calculations to explore the aggregate
      morphologies, which also provided valuable information on the influence of the
      additional alkylcarbonyl linkers. Our detailed spectroscopic and microscopic
      investigations revealed that the excellent optical properties of perylene
      bisimide chromophores can be used even in pure deionized water if their
      aggregation is efficiently suppressed.

PMID- 20143363
TI  - Self-assembly of calix[6]arene-diazapyrenium pseudorotaxanes: interplay of
      molecular recognition and ion-pairing effects.
AB  - The calix[6]arene wheel CX forms pseudorotaxane species with the diazapyrenium
      based axle 1.2PF(6) in CH(2)Cl(2) solution. The macrocyclic component is a
      heteroditopic receptor, which can complex the electron-acceptor moiety of the
      axle inside its cavity and the counterions with the ureidic groups on the upper
      rim. The self-assembled supramolecular species is a complex structure, which
      involves three components--the wheel, the axle and its counterions--that can
      mutually interact and affect. The stoichiometry of the resulting supramolecular
      complex depends on the nature and concentration of the counterions. Namely, it is
      observed that in dilute solution and with low-coordinating anions the axle takes
      two wheels, whereas with highly coordinating anions or in concentrated solutions
      the complex has a 1:1 stoichiometry.

PMID- 20143364
TI  - Cyclizations via frustrated Lewis pairs: Lewis acid induced intramolecular
      additions of amines to olefins and alkynes.

PMID- 20143365
TI  - Fast molecular rotor dynamics modulated by guest inclusion in a highly organized
      nanoporous organosilica.

PMID- 20143366
TI  - Methods to study GPI anchoring of proteins.

PMID- 20143367
TI  - A HTS assay for the detection of organophosphorus nerve agent scavengers.
AB  - A new pro-fluorescent probe aimed at a HTS assay of scavengers is able to
      selectively and efficiently cleave the P-S bond of organophosphorus nerve agents
      and by this provides non-toxic phosphonic acid has been designed and synthesised.
      The previously described pro-fluorescent probes were based on a conventional
      activated P-Oaryl bond cleavage, whereas our approach uses a self-immolative
      linker strategy that allows the detection of phosphonothioase activity with
      respect to a non-activated P-Salkyl bond. Further, we have also developed and
      optimised a high-throughput screening assay for the selection of decontaminants
      (chemical or biochemical scavengers) that could efficiently hydrolyse highly
      toxic V-type nerve agents. A preliminary screening, realised on a small alpha
      nucleophile library, allowed us to identify some preliminary "hits", among which
      pyridinealdoximes, alpha-oxo oximes, hydroxamic acids and, less active but more
      original, amidoximes were the most promising. Their selective phosphonothioase
      activity has been further confirmed by using PhX as the substrate, and thus they
      offer new perspectives for the synthesis of more potent V nerve agent scavengers.

PMID- 20143368
TI  - Activation instead of inhibition: targeting proenzymes for small-molecule
      intervention.

PMID- 20143369
TI  - Binuclear Ni(II)-DpaTyr complex as a high affinity probe for an oligo-aspartate
      Tag tethered to proteins.
AB  - A complementary recognition pair of a short-peptide tag and a small molecular
      probe is a versatile molecular tool for protein detection, handling, and
      purification, and so forth. In this manuscript, we report that the binuclear
      Ni(II)-DpaTyr (DpaTyr=bis((dipicolylamino)methyl)tyrosine) complex serves as a
      strong binding probe for an oligo-aspartate tag tethered to a protein. Among
      various binuclear metal complexes of M-DpaTyr (M=Zn(II), Ni(II), Mn(II), Cu(II),
      Cd(II), Co(III), and Fe(III)), we have found that Ni(II)-DpaTyr (1-2Ni(II))
      displays a strong-binding affinity (apparent binding constant: K(app)
      approximately 10(5) M(-1)) for an oligo-aspartate peptide under neutral aqueous
      conditions (50 mM HEPES, 100 mM NaCl, pH 7.2). Detailed isothermal-titration
      calorimetry (ITC) studies reveal that the tri-aspartate D3-tag (DDD) is an
      optimal sequence recognized by 1-2Ni(II) in a 1:1 binding stoichiometry. On the
      other hand, other metal complexes of DpaTyr, except for Ni(II)- and Zn(II)
      DpaTyr, show a negligible binding affinity for the oligo-aspartate peptide. The
      binding affinity was greatly enhanced in the pair between the dimer of Ni(II)
      DpaTyr and the repeated D3 tag peptide (D3x2), such as DDDXXDDD, on the basis of
      the multivalent coordination interaction between them. Most notably, a remarkably
      high-binding affinity (K(app)=2x10(9) M(-1)) was achieved between the Ni(II)
      DpaTyr dimer 4-4Ni(II) and the D3x2 tag peptide (DDDNGDDD). This affinity is
      approximately 100-fold stronger than that observed in the binding pair of the
      Zn(II)-DpaTyr (4-4Zn(II)) and the D4x2 tag (DDDDGDDDD), a useful tag-probe pair
      previously reported by us. The recognition pair of the Ni(II)-DpaTyr probe and
      the D3x2 tag can also work effectively on a protein surface, that is, 4-4Ni(II)
      is strongly bound to the FKBP12 protein tethered with the D3x2 tag (DDDNGDDD)
      with a large K(app) value of 5x10(8) M(-1). Taking advantage of the strong
      binding affinity, this pair was successfully applied to the selective
      inactivation of the tag-fused beta-galactosidase by using the chromophore
      assisted light inactivation (CALI) technique under crude conditions, such as cell
      lysate.

PMID- 20143370
TI  - Fluorescence turn-on sensing of lectins with mannose-substituted
      tetraphenylethenes based on aggregation-induced emission.
AB  - The synthesis of mannose-substituted tetraphenylethenes (TPEs) and their
      aggregation-induced emission (AIE) behavior, induced by interactions with
      concanavalin A (Con A), are reported. A mixture of the mannose-TPE conjugates and
      Con A in a buffer solution displays an intense blue emission on agglutination
      within a few seconds, which serves as a "turn-on" fluorescent sensor for lectins.
      The sensing is also selective: the conjugates act as a sensor for Con A, but do
      not sense a galactose-binding lectin, PNA. Con A-recognition is not affected even
      in the presence of other proteins in a mixture. The conjugates also exhibit high
      sensitivity to detect Con A. An increased sensitivity of the conjugates results
      if mannopyranoside substituents are linked to the TPE-core unit with a flexible
      chain and/or when the number of mannose residues increases.

PMID- 20143371
TI  - The site-selective molecular recognition of ternary architectures by using
      supramolecular nanoporous networks at a liquid-solid interface.

PMID- 20143372
TI  - Binding studies on CB[6] with a series of 1-alkyl-3-methylimidazolium ionic
      liquids in an aqueous system.
AB  - The host-guest chemistry between a series of 1-alkyl-3-methyl-imidazolium bromide
      ([C(n)mim]Br) guests and the macrocyclic host molecule cucurbit[6]uril (CB[6]) in
      an aqueous system is systematically studied in neutral aqueous media. Both 1D and
      2D NMR experiments in conjunction with isothermal titration calorimetry (ITC)
      unveil the binding characteristics of the host-guest interaction. Solution
      binding constants (K(a)) up to 10(5) M(-1) are measured directly. Additionally,
      this [C(n)mim]Br-CB[6] interaction was found to significantly increase the
      solubility of CB[6] in neutral water, in some cases by at least four orders of
      magnitude. From these studies, a detailed host-guest binding model has been
      constructed and is fully discussed. In this model, the delocalized positive
      charge on the imidazolium ring becomes partially localized on either one of the
      nitrogen atoms upon complexation with CB[6]. Localization of the positive charge
      is directly related to the length of the "1-alkyl" chain on the imidazolium ring,
      which causes an induced local dipole subsequently allowing for an ion-dipole
      interaction with the carbonyl portal of CB[6].

PMID- 20143373
TI  - Europium directed synthesis of enantiomerically pure dimetallic luminescent
      "squeezed" triple-stranded helicates; solution studies.

PMID- 20143374
TI  - Pd(II)-catalyzed highly selective arylation of allyl esters via C-H
      functionalization of unreactive arenes with retention of the traditional leaving
      group.

PMID- 20143375
TI  - Reductive benzylation of dimetallo hexaaryl[70]fullerenes on the equatorial
      region.
AB  - Dianions of dimetallic hexa(organo)[70]fullerene [(C(5)R(5))(2)Ru(2)C(70)Ar(6)](2
      ) (R=H, Me; Ar=Ph, 4-MeC(6)H(4), 4-tBuC(6)H(4)) react with benzylic bromide to
      yield the dibenzylated product dimetallic octa(organo)[70]fullerene
      (C(5)R(5))(2)Ru(2)C(70)Ar(6)(CH(2)Ar')(2) (Ar'=Ph, 4-MeO(2)CC(6)H(4)), where the
      benzylic groups are attached to the equatorial belt region of [70]fullerene; this
      region is generally considered to be rather unreactive. This unusual structure
      was unambiguously determined by X-ray crystallography. Theoretical studies on the
      electronic properties of the monoanionic intermediate indicated that the highest
      spin density resides on the two carbon atoms in the belt region; one of them then
      couples with a benzylic radical to yield the octa(organo)fullerene product after
      ionic substitution of the fullerene anion with a benzylic bromide.
      Electrochemical analysis of the hexa(organo) and octa(organo) ruthenium complexes
      suggests that the modification of the belt region does not affect the electronic
      communication between the two metal centers.

PMID- 20143376
TI  - Recyclable sulfonated amorphous carbon catalyzed friedel-crafts alkylation of
      indoles with alpha,beta-unsaturated carbonyl compounds in water.

PMID- 20143377
TI  - A structural model for HPO(4) (2-) binding to Co in a water oxidation catalyst.

PMID- 20143378
TI  - Textile-compatible substrate electrodes with electrodeposited ZnO--a new pathway
      to textile-based photovoltaics.
AB  - A strategy is presented to realize textile-based photovoltaic cells motivated by
      developments of textile-based electronics and their demand of grid-independent
      energy supply. Beyond this, a development of textile-based photovoltaics also
      represents an attractive pathway towards very flexible and rugged solar cells.
      The need for compatibility of an appropriate photovoltaic technology with the
      physical limitations of textiles is stressed. Electrodeposition from aqueous
      solutions is presented as a successful strategy to realize semiconductor
      structures on textiles and detailed control and influence of the deposition
      conditions is discussed. The role of microelectrode effects, options of forced
      convection, deposition under pulsed potential, alternative deposition baths and
      different substrate metals are emphasized. An active electrode material is
      presented which reaches a conversion efficiency close to the 1% limit under AM
      1.5 illumination conditions and thereby opens the door for a further optimization
      towards devices of technical interest.

PMID- 20143379
TI  - Differential behavior of amino-imino constitutional isomers in nonlinear optical
      processes.
AB  - A detailed study of the "blocked" amino-imino tautomers derived from N-acridine
      substituted 2-aminobenzothiazole--and their effect on the nonlinear optical
      response--is presented. The synthesis, characterization, and nonlinear optical
      properties of these frozen tautomers, namely, N-methyl-N-(2-nitroacridin-6-yl)-2
      aminobenzothia-zole and 3-methyl-N-(7-nitroacridin-3-yl)-2-iminobenzothiazole,
      are reported. A theoretical model based on valence-bond theory is also proposed
      and used to analyze the effects of the nuclear configuration corresponding to
      each frozen tautomer structure. In the present case, the aromatic form and the
      allylic-anion-like system of the -N-C-N- group inherent to each isomer are
      crucial for understanding and analyzing the different responses of each "blocked"
      tautomer.

PMID- 20143380
TI  - Highly stable lithium storage performance in a porous carbon/silicon
      nanocomposite.

PMID- 20143381
TI  - Marine huge molecules: the longest carbon chains in natural products.
AB  - Marine huge polyol and polyether compounds are remarkable molecules owing to
      their extraordinary structures and significant biological activities. Currently,
      palytoxin and maitotoxin are believed to have the longest carbon chains in nature
      (more than 100 A in length), except for biopolymers. The structural properties of
      such marine huge molecules are highlighted, especially with regard to the length
      and shape of their carbon chains.

PMID- 20143382
TI  - A multifaith spiritually based intervention for generalized anxiety disorder: a
      pilot randomized trial.
AB  - This pilot trial evaluated the efficacy of a multifaith spiritually based
      intervention (SBI) for generalized anxiety disorder (GAD). Patients meeting DSM
      IV criteria for GAD of at least moderate severity were randomized to either 12
      sessions of the SBI (n=11) delivered by a spiritual care counselor or 12 sessions
      of psychologist-administered cognitive-behavioral therapy (CBT; n=11). Outcome
      measures were completed at baseline, post-treatment, and 3-month and 6-month
      follow-ups. Primary efficacy measures included the Hamilton Anxiety Rating Scale,
      Beck Anxiety Inventory, and Penn State Worry Questionnaire. Data analysis was
      performed on the intent-to-treat sample using the Last Observation Carried
      Forward method. Eighteen patients (82%) completed the study. The SBI produced
      robust and clinically significant reductions from baseline in psychic and somatic
      symptoms of GAD and was comparable in efficacy to CBT. A reduction in depressive
      symptoms and improvement in social adjustment was also observed. Treatment
      response occurred in 63.6% of SBI-treated and 72.3% of CBT-treated patients.
      Gains were maintained at 3-month and 6-month follow-ups. These preliminary
      findings are encouraging and suggest that a multifaith SBI may be an effective
      treatment option for GAD. Further randomized controlled trials are needed to
      establish the efficacy of this intervention.

PMID- 20143383
TI  - Cortical gamma-oscillations modulated by auditory-motor tasks-intracranial
      recording in patients with epilepsy.
AB  - Human activities often involve hand-motor responses following external auditory
      verbal commands. It has been believed that hand movements are predominantly
      driven by the contralateral primary sensorimotor cortex, whereas auditory-verbal
      information is processed in both superior temporal gyri. It remains unknown
      whether cortical activation in the superior temporal gyrus during an auditory
      motor task is affected by laterality of hand-motor responses. Here, event-related
      gamma-oscillations were intracranially recorded as quantitative measures of
      cortical activation; we determined how cortical structures were activated by
      auditory-cued movement using each hand in 15 patients with focal epilepsy.
      Auditory-verbal stimuli elicited augmentation of gamma-oscillations in a
      posterior portion of the superior temporal gyrus, whereas hand-motor responses
      elicited gamma-augmentation in the pre- and postcentral gyri. The magnitudes of
      such gamma-augmentation in the superior temporal, precentral, and postcentral
      gyri were significantly larger when the hand contralateral to the recorded
      hemisphere was required to be used for motor responses, compared with when the
      ipsilateral hand was. The superior temporal gyrus in each hemisphere might play a
      greater pivotal role when the contralateral hand needs to be used for motor
      responses, compared with when the ipsilateral hand does.

PMID- 20143384
TI  - Left cytoarchitectonic BA 44 processes syntactic gender violations in determiner
      phrases.
AB  - Recent neuroimaging studies make contradictory predictions about the involvement
      of left Brodmann's area (BA) 44 in processing local syntactic violations in
      determiner phrases (DPs). Some studies suggest a role for BA 44 in detecting
      local syntactic violations, whereas others attribute this function to the left
      premotor cortex. Therefore, the present event-related functional magnetic
      resonance imaging (fMRI) study investigated whether left-cytoarchitectonic BA 44
      was activated when German DPs involving syntactic gender violations were compared
      with correct DPs (correct: 'der Baum'-the[masculine] tree[masculine]; violated:
      'das Baum'--the[neuter] tree[masculine]). Grammaticality judgements were made for
      both visual and auditory DPs to be able to generalize the results across
      modalities. Grammaticality judgements involved, among others, left BA 44 and left
      BA 6 in the premotor cortex for visual and auditory stimuli. Most importantly,
      activation in left BA 44 was consistently higher for violated than for correct
      DPs. This finding was behaviourally corroborated by longer reaction times for
      violated versus correct DPs. Additional brain regions, showing the same effect,
      included left premotor cortex, supplementary motor area, right middle and
      superior frontal cortex, and left cerebellum. Based on earlier findings from the
      literature, the results indicate the involvement of left BA 44 in processing
      local syntactic violations when these include morphological features, whereas
      left premotor cortex seems crucial for the detection of local word category
      violations.

PMID- 20143385
TI  - Cortical responses to consciousness of schematic emotional facial expressions: a
      high-resolution EEG study.
AB  - Is conscious perception of emotional face expression related to enhanced cortical
      responses? Electroencephalographic data (112 channels) were recorded in 15 normal
      adults during the presentation of cue stimuli with neutral, happy or sad
      schematic faces (duration: "threshold time" inducing about 50% of correct
      recognitions), masking stimuli (2 s), and go stimuli with happy or sad schematic
      faces (0.5 s). The subjects clicked left (right) mouse button in response to go
      stimuli with happy (sad) faces. After the response, they said "seen" or "not
      seen" with reference to previous cue stimulus. Electroencephalographic data
      formed visual event-related potentials (ERPs). Cortical sources of ERPs were
      estimated by LORETA software. Reaction time to go stimuli was generally shorter
      during "seen" than "not seen" trials, possibly due to covert attention and
      awareness. The cue stimuli evoked four ERP components (posterior N100, N170,
      P200, and P300), which had similar peak latency in the "not seen" and "seen"
      ERPs. Only N170 amplitude showed differences in amplitude in the "seen" versus
      "not seen" ERPs. Compared to the "not seen" ERPs, the "seen" ones showed
      prefrontal, premotor, and posterior parietal sources of N170 higher in amplitude
      with the sad cue stimuli and lower in amplitude with the neutral and happy cue
      stimuli. These results suggest that nonconscious and conscious processing of
      schematic emotional facial expressions shares a similar temporal evolution of
      cortical activity, and conscious processing induces an early enhancement of
      bilateral cortical activity for the schematic sad facial expressions (N170).

PMID- 20143386
TI  - 3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI.
AB  - We applied the hippocampal radial atrophy mapping technique to the baseline and
      follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment
      (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative
      Study MCI Donepezil/Vitamin E trial. Sixty percent of the subjects with none to
      mild hippocampal atrophy rated with the visual medial temporal atrophy rating
      scale (MTA score < 2) and 33.8% of the subjects with moderate to severe (MTA > or
      = 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year
      follow-up. MTA > or = 2 showed a trend for greater left sided hippocampal atrophy
      versus MTA < 2 groups at baseline (P(corrected) = 0.08). Higher MTA scores were
      associated with progressive atrophy of the subiculum and the CA1-3 subregions.
      The MTA < 2 group demonstrated significant bilateral atrophy progression at
      follow-up (left P(corrected) = 0.008; right P(corrected) = 0.05). Relative to MTA
      < 2 nonconverters, MTA < 2 converters showed further involvement of the subiculum
      and CA1 and additional involvement of CA2-3 at follow-up. Right CA1 atrophy was
      significantly associated with conversion to dementia (for 1 mm greater right CA1
      radial distance subjects had 50% reduced hazard for conversion). Greater CA1 and
      subicular atrophy can be demonstrated early and is predictive of future
      conversion to AD, whereas CA2-3 involvement becomes more evident as the disease
      progresses.

PMID- 20143387
TI  - Distortion correction for diffusion-weighted MRI tractography and fMRI in the
      temporal lobes.
AB  - Single shot echo-planar imaging (EPI) sequences are currently the most commonly
      used sequences for diffusion-weighted imaging (DWI) and functional magnetic
      resonance imaging (fMRI) as they allow relatively high signal to noise with rapid
      acquisition time. A major drawback of EPI is the substantial geometric distortion
      and signal loss that can occur due to magnetic field inhomogeneities close to air
      tissue boundaries. If DWI-based tractography and fMRI are to be applied to these
      regions, then the distortions must be accurately corrected to achieve meaningful
      results. We describe robust acquisition and processing methods for correcting
      such distortions in spin echo (SE) EPI using a variant of the reversed direction
      k space traversal method with a number of novel additions. We demonstrate that
      dual direction k space traversal with maintained diffusion-encoding gradient
      strength and direction results in correction of the great majority of eddy
      current-associated distortions in DWI, in addition to those created by variations
      in magnetic susceptibility. We also provide examples to demonstrate that the
      presence of severe distortions cannot be ignored if meaningful tractography
      results are desired. The distortion correction routine was applied to SE-EPI fMRI
      acquisitions and allowed detection of activation in the temporal lobe that had
      been previously found using PET but not conventional fMRI.

PMID- 20143388
TI  - Check your cultures! A list of cross-contaminated or misidentified cell lines.
AB  - Continuous cell lines consist of cultured cells derived from a specific donor and
      tissue of origin that have acquired the ability to proliferate indefinitely.
      These cell lines are well-recognized models for the study of health and disease,
      particularly for cancer. However, there are cautions to be aware of when using
      continuous cell lines, including the possibility of contamination, in which a
      foreign cell line or microorganism is introduced without the handler's knowledge.
      Cross-contamination, in which the contaminant is another cell line, was first
      recognized in the 1950s but, disturbingly, remains a serious issue today. Many
      cell lines become cross-contaminated early, so that subsequent experimental work
      has been performed only on the contaminant, masquerading under a different name.
      What can be done in response-how can a researcher know if their own cell lines
      are cross-contaminated? Two practical responses are suggested here. First, it is
      important to check the literature, looking for previous work on cross
      contamination. Some reports may be difficult to find and to make these more
      accessible, we have compiled a list of known cross-contaminated cell lines. The
      list currently contains 360 cell lines, drawn from 68 references. Most
      contaminants arise within the same species, with HeLa still the most frequently
      encountered (29%, 106/360) among human cell lines, but interspecies contaminants
      account for a small but substantial minority of cases (9%, 33/360). Second, even
      if there are no previous publications on cross-contamination for that cell line,
      it is essential to check the sample itself by performing authentication testing.

PMID- 20143389
TI  - The marine compound spongistatin 1 targets pancreatic tumor progression and
      metastasis.
AB  - Treatment of pancreatic cancer remains a major challenge and new anticancer drugs
      are urgently required. Our study presents the marine natural compound
      spongistatin 1 as a promising experimental drug. Spongistatin 1 was applied in an
      orthotopic in vivo model of human pancreatic cancer. Spongistatin 1 significantly
      reduced tumor growth, which correlates with a strong apoptosis induction (DNA
      fragmentation) and long-term effects on clonogenic survival of pancreatic tumor
      cells (L3.6pl) in vitro. In addition, the formation of metastasis was reduced in
      spongistatin 1-treated mice, which is in line with a diminished MMP-9 activity in
      tumor tissue determined by zymography. Based on the pronounced efficacy of
      spongistatin 1, the underlying mechanisms were studied in more detail. In vitro
      adhesion, as well as migration, and invasion assays showed spongistatin 1 to
      influence these critical steps in the metastatic cascade. Furthermore,
      spongistatin 1 induced anoikis in L3.6pl cells. Exposure to spongistatin 1 leads
      to phosphorylation, and thus inactivation of the antiapoptotic protein Bcl-2 in
      pancreatic tumor cells. siRNA experiments silencing Bcl-2 suggest a role of Bcl-2
      in anoikis and cell migration. Taken together, spongistatin 1 not only proved to
      be a potent experimental drug but also served as a chemical tool to examine the
      role of the antiapoptotic protein Bcl-2 in pancreas carcinoma, thereby supporting
      the hypothesis of a link between apoptosis signaling and metastasis.

PMID- 20143390
TI  - Plasma decorin predicts the presence of esophageal squamous cell carcinoma.
AB  - Using a microarray technique, we found decorin to be underexpressed, but
      osteopontin (OPN) to be overexpressed, in esophageal squamous cell carcinoma
      (ESCC). This study aims to examine whether plasma decorin and OPN plus personal
      substances use (tobacco, alcohol and areca) can serve as suitable clinical
      markers to predict the presence of ESCC. In total, 570 archived plasma specimens
      (275 patients and 295 controls) were collected from 2 medical centers in Taiwan
      between 2000 and 2008. Decorin and OPN protein levels were measured by ELISA.
      Means and standard deviation of plasma decorin were 5.6 + or - 3.6 ng/ml in case
      patients, which were significantly lower than those in controls (7.8 + or - 3.1,
      p < 0.0001). Plasma OPN levels in case patients were not significantly different
      from controls (p = 0.33). When compared to subjects with the lowest quartile of
      plasma decorin, those with the highest quartile one had a significantly lower
      risk to have ESCC (Adjusted OR = 0.03, p < 0.001). Receiver operator
      characteristic (ROC) analysis was performed for the combination of plasma decorin
      and 3 substances use (smoke, alcohol and areca) for the patients compared with
      the controls. The area under the curve was 88.6% and the optimal cut-point of ROC
      curve (any 3 factors) had 73.5% sensitivity and 90.2% specificity with
      approximately 82% of corrected classification. Plasma decorin, but not OPN, is a
      potential clinical marker for the detection of ESCC. When plasma decorin plus the
      use of the 3 substances are combined, this factor cluster could be used to detect
      the presence of ESCC.

PMID- 20143391
TI  - In vivo tumor suppression activity by T cell-specific T-bet restoration.
AB  - T-box-containing protein expressed in T cells (T-bet) is a master transcription
      factor for the development of interferon (IFN) gamma-producing T helper 1 (Th1)
      cells and also functions in other immune cells including natural killer (NK),
      cytotoxic T lymphocytes and dendritic cells. T-bet-deficient mice increased
      susceptibility to viral infection and tumor development due to the defective
      functions of immune cells. T-bet is known to play a key role in NK-mediated
      antimetastatic response; however, it remains to be characterized whether T-bet is
      essential for in vivo tumor suppression mediated by T cells. Here, we have
      investigated in vivo tumor suppression effect of T-bet-restored T cells using T
      cell-specific and inducible T-bet transgenic mice generated in a T-bet-deficient
      background. T-bet-null mice increased susceptibility to tumor development,
      whereas induction of T cell-specific T-bet expression upon melanoma cell
      injection substantially suppressed tumor development by inducing IFNgamma
      production in T cells and tumor cell apoptosis. Late induction of T-bet
      expression in tumor-bearing mice produced comparable amounts of IFNgamma with
      control and significantly decreased tumor volume. In addition, increased melanoma
      lung metastasis in T-bet-deficient mice was strikingly inhibited by T-bet
      restoration in T cells. Intravenous injection of activated Th1 cells, not T-bet
      null Th1 cells, attenuated metastatic melanoma progression, in addition,
      restoration of T-bet in T-bet-null Th1 cells certainly retrieved antimetastatic
      activity. These results suggest that T-bet expression in T cells is crucial for
      the control of tumor development and antimetastatic activity.

PMID- 20143392
TI  - Elevated expression of tumor necrosis factor-alpha signaling molecules in colonic
      tumors of Zucker obese (fa/fa) rats.
AB  - Zucker obese rats are highly sensitive to colon cancer and possess a plethora of
      metabolic abnormalities including elevated levels of cytokine tumor necrosis
      factor-alpha (TNF-alpha). The main objective of this study was to determine if
      physiologically elevated TNF-alpha affects colonic tumor phenotype with regard to
      an altered TNF-alpha signaling pathway. Zucker obese (fa/fa, homozygous recessive
      for dysfunctional leptin receptors), Zucker lean (Fa/fa, Fa/Fa) and Sprague
      Dawley (SD) rats were injected twice with azoxymethane (10 mg/kg) over 2 weeks.
      After 30 weeks, the animals were terminated and physiological and tumor
      parameters were assessed. Obese rats had notably higher body and organ weights as
      well as plasma TNF-alpha, insulin and leptin levels than lean or SD animals. A
      100% tumor incidence and significantly higher tumor size, multiplicity and burden
      were found in obese rats compared to the lean group that had 47.8% tumor
      incidence. The SD group had the lowest tumor incidence (20.0%). Tumors from obese
      animals had higher protein levels of TNF-alpha, TNF-alpha-receptor-2 (TNFR2),
      nuclear transcription factor-kappaB (NF-kappaB) and IkappaB-kinasebeta (IKKbeta)
      compared to lean animals. In both obese and lean groups, expression levels of
      these proteins were higher in tumors than in surrounding, normal-appearing
      colonic mucosae. These findings support an important role for TNF-alpha signaling
      in tumorigenesis and demonstrate that tumors growing in an obese state had
      significantly different expression levels of TNFR2 and NF-kappaB, proteins known
      to play a critical role in growth and survival, than those growing in the lean
      state. It is concluded that the physiological state of the host intricately
      affects tumor phenotype.

PMID- 20143393
TI  - Expression of laminin gamma2 chain monomer enhances invasive growth of human
      carcinoma cells in vivo.
AB  - Laminin gamma2 chain is a subunit of the heterotrimeric basement membrane protein
      laminin-332 (alpha3beta3gamma2). The gamma2 chain is highly expressed by human
      cancers at the invasion fronts and this expression correlates with poor prognosis
      of the cancers. Our previous study showed that the gamma2 chain is expressed as a
      monomer form in invading carcinoma cells. However, the role of the gamma2 protein
      in tumor invasion remains unknown. Here, we demonstrate that the monomeric gamma2
      chain promotes invasive growth of human cancer cells in vivo. First, we analyzed
      regulatory factors for the gamma2 chain expression using 2 gastric carcinoma cell
      lines. It was found that tumor necrosis factor-alpha, by itself or in a
      combination with transforming growth factor-beta1, strongly induced the secretion
      of the monomeric gamma2 chain. In addition, epidermal growth factor families
      appeared to function as the gamma2 chain inducers in human cancers. Next, we
      established T-24 bladder carcinoma cell lines expressing the full-length or the
      short arm of the laminin gamma2 chain. When these cell lines were i.p. injected
      into nude mice, they produced larger tumors in the abdominal cavity and showed
      much stronger invasive growth onto the diaphragms than the control cell line. The
      gamma2-expressing T-24 cells often produced ascites fluid, but scarcely the
      control cells. In culture, the gamma2-expressing cells migrated through Matrigel
      more efficiently than the control cells. These findings imply that the gamma2
      monomer is induced in human cancers by inflammatory and stromal cytokines and
      promotes their invasive growth in vivo.

PMID- 20143394
TI  - Estimating the attributable fraction for melanoma: a meta-analysis of pigmentary
      characteristics and freckling.
AB  - Epidemiologic research has demonstrated convincingly that certain pigmentary
      characteristics are associated with increased relative risks of melanoma; however
      there has been no comprehensive review to rank these characteristics in order of
      their importance on a population level. We conducted a systematic review of the
      literature and meta-analysis to quantify the contribution of pigmentary
      characteristics to melanoma, estimated by the population-attributable fraction
      (PAF). Eligible studies were those that permitted quantitative assessment of the
      association between histologically confirmed melanoma and hair colour, eye
      colour, skin phototype and presence of freckling; we identified 66 such studies
      using citation databases, followed by manual review of retrieved references. We
      calculated summary relative risks using weighted averages of the log RR, taking
      into account random effects, and used these to estimate the PAF. The pooled RRs
      for pigmentary characteristics were: 2.64 for red/red-blond, 2.0 for blond and
      1.46 for light brown hair colour (vs. dark); 1.57 for blue/blue-grey and 1.51 for
      green/grey/hazel eye colour (vs. dark); 2.27, 1.99 and 1.35 for skin phototypes
      I, II and III respectively (vs. IV); and 1.99 for presence of freckling. The
      highest PAFs were observed for skin phototypes 1/II (0.27), presence of freckling
      (0.23), and blond hair colour (0.23). For eye colour, the PAF for blue/blue-grey
      eye colour was higher than for green/grey/hazel eye colour (0.18 vs. 0.13). The
      PAF of melanoma associated with red hair colour was 0.10. These estimates of
      melanoma burden attributable to pigmentary characteristics provide a basis for
      designing prevention strategies for melanoma.

PMID- 20143395
TI  - Allergies, obesity, other risk factors and survival from pancreatic cancer.
AB  - Survival from pancreatic adenocarcinoma remains extremely poor, approximately 5%
      at 5 years. Risk factors include smoking, high body mass index (BMI), family
      history of pancreatic cancer, and long-standing diabetes; in contrast, allergies
      are associated with reduced risk. Little is known about associations between
      these factors and survival. We analyzed overall survival in relation to risk
      factors for 475 incident cases who took part in a hospital based case-control
      study. Analyses were conducted separately for those who did (160) and did not
      (315) undergo tumor resection. Kaplan-Meier methods were used to describe
      survival according to smoking, BMI, family history, diabetes, and presence of
      allergies. Cox proportional hazards models were used to adjust for covariates.
      There was no association with survival based on smoking, family history, or
      history of diabetes in either group. Among patients with resection, those with
      allergies showed nonstatistically significant longer survival, a median of 33.1
      months (95% CI: 19.0-52.5) vs. 21.8 months (95% CI: 18.0-33.1), p = 0.25. The
      adjusted hazard ratio (HR) was 0.72 (95% CI: 0.43-1.23), p = 0.23. Among patients
      without resection, those with self-reported allergies survived significantly
      longer than those without allergies: 13.3 months (95% CI: 10.6-16.9) compared to
      10.4 months (95% CI: 8.8-11.0), p = 0.04, with an adjusted HR of 0.68 (95% CI:
      0.49-0.95), p = 0.02. Obesity was nonsignificantly associated with poorer
      survival, particularly in the resected group (HR = 1.62, 95% CI: 0.76-3.44). The
      mechanisms underlying the association between history of allergies and improved
      survival are unknown. These novel results need to be confirmed in other studies.

PMID- 20143396
TI  - Antabuse (disulfiram) as a pilot case of nonprofit drug.

PMID- 20143397
TI  - Substantial regional differences in human herpesvirus 8 seroprevalence in sub
      Saharan Africa: insights on the origin of the "Kaposi's sarcoma belt".
AB  - Equatorial Africa has among the highest incidences of Kaposi's sarcoma (KS) in
      the world, thus earning the name "KS Belt." This was the case even before the HIV
      epidemic. To date, there is no clear evidence that HHV-8 seroprevalence is higher
      in this region but interpretation of the available literature is tempered by
      differences in serologic assays used across studies. We examined representatively
      sampled ambulatory adults in Uganda, which is in the "KS Belt," and in Zimbabwe
      and South Africa which are outside the Belt, for HHV-8 antibodies. All serologic
      assays were uniformly performed in the same reference laboratory by the same
      personnel. In the base-case serologic algorithm, seropositivity was defined by
      reactivity in an immunofluorescence assay or in 2 enzyme immunoassays. A total of
      2,375 participants were examined. In Uganda, HHV-8 seroprevalence was high early
      in adulthood (35.5% by age 21) without significant change thereafter. In
      contrast, HHV-8 seroprevalence early in adulthood was lower in Zimbabwe and South
      Africa (13.7 and 10.8%, respectively) but increased with age. After age
      adjustment, Ugandans had 3.24-fold greater odds of being HHV-8 infected than
      South Africans (p < 0.001) and 2.22-fold greater odds than Zimbabweans (p <
      0.001). Inferences were unchanged using all other serologic algorithms evaluated.
      In conclusion, HHV-8 infection is substantially more common in Uganda than in
      Zimbabwe and South Africa. These findings help to explain the high KS incidence
      in the "KS Belt" and underscore the importance of a uniform approach to HHV-8
      antibody testing.

PMID- 20143398
TI  - Deficiency or blockade of angiotensin II type 2 receptor delays tumorigenesis by
      inhibiting malignant cell proliferation and angiogenesis.
AB  - Despite significant expression level in cancer cells, the role of the angiotensin
      II Type 2 receptor (AT2R) in cancer progression remains poorly understood. We
      aimed to investigate the involvement of AT2R in tumorigenesis, hypothesizing a
      role in tumor cell proliferation and/or tumor angiogenesis. Two animal tumor
      models were used: fibrosarcoma induced by 3-methylcholanthrene (3-MCA) in FVB/N
      mice invalidated for AT2R (AT2R-KO) and carcinoma LL/2 cells injected in C57BL/6N
      mice treated with AT2R antagonist PD123,319. Tumor growth was monitored,
      microvascular density (MVD) evaluated by CD31 staining. Proliferation index of
      LL/2 and 3-MCA tumor cells was evaluated by expression of Ki-67. Angiogenesis was
      assessed by aorta ring assay and angiogenic mediators' expression by real-time RT
      PCR. Tumor induction by 3-MCA was significantly delayed in AT2R-KO compared to
      wild-type mice (56 days vs. 28 days). Tumorigenesis following LL/2 cell injection
      in mice was also significantly reduced by early administration of the antagonist
      PD123,319. In vitro, inactivation or invalidation of AT2R inhibited proliferation
      of LL/2 and 3-MCA tumor cells, respectively. Tumor MVD was reduced in mice
      treated early with PD123,319. Ex vivo experiments revealed a significant decrease
      in angiogenesis after PD123,319 treatment or in AT2R-KO mice. Finally, we
      identified vascular endothelial growth factor (VEGF) as a soluble proangiogenic
      factor produced by LL/2 cells and we showed that in LL/2 and 3-MCA tumor cells,
      inhibition or deficiency of AT2R was associated with impaired production of
      proangiogenic factors included VEGF. This study uncovered novel mechanisms by
      which AT2R would promote tumor development, favoring both malignant cell
      proliferation and tumor angiogenesis.

PMID- 20143399
TI  - The BCR/ABL-inhibitors imatinib, nilotinib and dasatinib differentially affect NK
      cell reactivity.
AB  - In chronic myeloid leukemia (CML), BCR/ABL-mediated oncogenic signaling can be
      targeted with the BCR/ABL-inhibitors Imatinib, Nilotinib and Dasatinib. However,
      these agents may also affect anti-tumor immunity. Here, we analyzed the effects
      of the 3 BCR/ABL-inhibitors on natural killer (NK) cell reactivity. Exposure of
      CML cells (K562, Meg-01) to pharmacological concentrations of Imatinib, Nilotinib
      and Dasatinib diminished expression of ligands for the activating immunoreceptor
      NKG2D to a similar extent. This resulted in comparably reduced NK cell
      cytotoxicity and IFN-gamma production. When direct effects on NK cell responses
      to K562 and primary CML cells as well as activating cytokines were studied,
      Dasatinib was found to abrogate NK cytotoxicity and cytokine production.
      Nilotinib did not alter cytotoxicity but, at high levels, impaired NK cytokine
      production, while Imatinib had no direct influence on NK cell reactivity. Of
      note, Nilotinib, but not the other BCR/ABL-inhibitors increased cell death within
      the preferentially cytokine-secreting CD56(bright)CD16(-) NK cell subset, which
      may, at least in part, serve to explain the effect of Nilotinib on NK cytokine
      production. Analysis of NK cell signaling revealed that Dasatinib inhibited
      proximal signaling events leading to decreased phosphorylation of PI3K and ERK
      that are crucial for NK cell reactivity. Imatinib and Nilotinib, in contrast,
      showed no relevant effect on NK cell PI3K or ERK activity. In light of the
      potential role of NK cells in the immunesurveillance of residual leukemia and for
      future combinatory immunotherapeutic approaches, our data indicate that choice
      and dosing of the most suitable BCR/ABL-inhibitor for a given patient require
      careful consideration.

PMID- 20143400
TI  - Humanities in Gross Anatomy Project: a novel humanistic learning tool at Des
      Moines University.
AB  - Gross anatomy affords physical therapy students an opportunity to discover human
      morphology by intimately studying the dead. Moreover, it also exposes future
      physical therapists to the humanistic aspects of the profession. In 2007, anatomy
      faculty decided to socialize students to the humanities with a new course
      requirement: Humanities in Gross Anatomy Project (HuGA) Project. At the end of
      the course, students, either individually or as a group, submitted a project that
      described how they had been personally touched by the donor's gift and how the
      gift contributed to their professional growth and education. The submission could
      be in the form of a narrative, poem, song, video, etc. All students met the three
      grading criteria that were established; thus taking the first step in socializing
      themselves to the humanistic domain of their professional education. In summary,
      the HuGA project is a novel educational tool that formally provided physical
      therapy students with humanistic learning opportunities in a gross anatomy course
      and appeared to facilitate reflective learning. The utilization of reflection as
      it relates to clinical decision making and patient interaction is critical for
      physical therapy practice.

PMID- 20143401
TI  - Protein fraction isolated from epididymal fluid re-associates sperm in vitro:
      possible role of serpins in rat rosettes assembly.
AB  - In many mammalian species, sperm associate as a consequence of the epididymal
      transit. From the classic Rouleaux in guinea pig to the most recent work in mouse
      and echidna, authors have focused mainly on a detailed morphological description
      of this phenomenon. Some of these articles have also begun to describe the nature
      of the material present between sperm heads. Here, we try to better understand
      the factor/s involved in rat sperm association (Rosette). Based on previous work
      describing the appearance of Rosettes in the distal segments of the rat
      epididymis, we consider that sperm during their transit must be in contact with
      factor/s present in the caudal lumen in order to associate with each other. By an
      in vitro sperm re-associating assay, we try to determine the in vivo phenomenon
      observed in the lumen. The assay consists of co-incubating non-associated sperm
      with several protein fractions obtained from epididymal caudal fluid. After
      establishing the most active fraction, the proteins were characterized by MALDI
      TOF mass spectrometry. Among the proteins we found two members of the serine
      protease inhibitors family; an alpha-1 antitrypsin and a new protein with an
      alpha-1 antitrypsin like domain which includes a sequence compatible with the
      serpins' reactive center loop. These serpins may play a role in the
      assembly/disassembly process of Rosettes by modulating lumenal protease activity.
      Finally, a biochemical-morphological model which explains the sperm-proteases
      interaction was proposed.

PMID- 20143402
TI  - Chromosome 8p11.2 translocations: prevalence, FISH analysis for FGFR1 and MYST3,
      and clinicopathologic correlates in a consecutive cohort of 13 cases from a
      single institution.
AB  - Chromosome 8p11.2 translocations result in diverse oncogenic fusion genes
      involving FGFR1 or MYST3. Among 24,262 unique patient cytogenetic studies
      performed at the Mayo Clinic, 8p11.2 translocations were identified in 14 cases (
      approximately 0.06%). FISH analysis was performed in 13 patients (12 had myeloid
      neoplasms) and revealed abnormalities of MYST3 (n = 4) or FGFR1 (n = 4) in eight
      patients. MYST3 abnormalities were associated with acute myeloid leukemia (AML),
      M4 in three and M6 in one. Three of the four FGFR1-rearranged cases were
      associated with myeloproliferative neoplasms but none, including the two with
      sole 8p11.2, displayed the typical phenotype for stem cell leukemia/lymphoma
      (SCLL) and only one had eosinophilia; the fourth case had AML-M4. FISH did not
      reveal FGFR1 involvement in the one patient with SCLL. We conclude that neither
      the SCLL phenotype nor blood eosinophilia is a consistent feature of FGFR1
      associated 8p11.2 translocations; conversely, FISH might not always reveal FGFR1
      involvement in typical SCLL.

PMID- 20143403
TI  - Deciphering the path ahead in myelodysplastic syndrome.

PMID- 20143404
TI  - Pseudo-Gaucher cells in sickle cell anemia.

PMID- 20143405
TI  - Magnetic resonance evaluation of hepatic and myocardial iron deposition in
      transfusion-independent thalassemia intermedia compared to regularly transfused
      thalassemia major patients.

PMID- 20143406
TI  - Polyelectrolyte stabilized drug nanoparticles via flash nanoprecipitation: a
      model study with beta-carotene.
AB  - Polyelectrolyte protected beta-carotene nanoparticles (nanosuspensions) with
      average diameter of <100 nm were achieved by turbulent mixing and flash
      nanoprecipitation (FNP). Three types of multi-amine functional polyelectrolytes,
      epsilon-polylysine (epsilon-PL), poly(ethylene imine) (PEI), and chitosan, were
      investigated to electrosterically protect the nanoparticles. Particle size and
      distribution were measured by dynamic light scattering (DLS); particles were
      imaged via scanning electron microscopy (SEM) and cryogenic transmission electron
      microscopy (cryo-TEM). Low pH and high polyelectrolyte molecular weight gave the
      smallest and most stable particles. High drug loading capacity, >80 wt%, was
      achieved by using either PEI or chitosan. X-ray diffraction (XRD) patterns showed
      that beta-carotene nanoparticles were amorphous. These findings open the way for
      utilization of FNP for preparation of nanoparticles with enhanced bioavailability
      for highly water insoluble drugs.

PMID- 20143407
TI  - Chondroitin-6-sulfate incorporation and mechanical stimulation increase MSC
      collagen sponge construct stiffness.
AB  - Using functional tissue engineering principles, our laboratory has produced
      tendon repair tissue which matches the normal patellar tendon force-displacement
      curve up to 32% of failure. This repair tissue will need to withstand more
      strenuous activities, which can reach or even exceed 40% of failure force. To
      improve the linear stiffness of our tissue engineered constructs (TECs) and
      tissue engineered repairs, our lab is incorporating the glycosaminoglycan
      chondroitin-6-sulfate (C6S) into a type I collagen scaffold. In this study, we
      examined the effect of C6S incorporation and mechanical stimulation cycle number
      on linear stiffness and mRNA expression (collagen types I and III, decorin and
      fibronectin) for mesenchymal stem cell (MSC)-collagen sponge TECs. The TECs were
      fabricated by inoculating MSCs at a density of 0.14 x 10(6) cells/construct onto
      pre-cut scaffolds. Primarily type I collagen scaffold materials, with or without
      C6S, were cultured using mechanical stimulation with three different cycle
      numbers (0, 100, or 3,000 cycles/day). After 2 weeks in culture, TECs were
      evaluated for linear stiffness and mRNA expression. C6S incorporation and cycle
      number each played an important role in gene expression, but only the interaction
      of C6S incorporation and cycle number produced a benefit for TEC linear
      stiffness.

PMID- 20143408
TI  - Adenosine A(2)A receptor but not HIF-1 mediates Tyrosine hydroxylase induction in
      hypoxic PC12 cells.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of
      catecholamines released by oxygen-sensitive cells in response to hypoxic
      conditions. Adenosine is released in response to hypoxia in the central nervous
      system and CGS21680, an adenosine A(2)A receptor agonist, induces TH
      transcription. As we have previously demonstrated the A(2)A receptor-mediated
      induction of HIF-1 in macrophages and hepatocytes, we investigated the
      involvement of HIF-1 in the adenosine-mediated activation of TH expression.
      Exposure to adenosine or CGS21680 increased TH mRNA and protein levels in PC12
      cells. Transcription of a reporter gene under the control of the wild type rat TH
      promoter was induced 3.5-fold in CGS21680-treated cells, but neither the mutation
      of the hypoxia responsive element in the TH promoter nor the co-transfection of a
      dominant negative of the HIF-1 beta subunit prevented the increase in
      transcription; furthermore, CGS21680 increased CREB binding activity but did not
      induce HIF-1 DNA binding activity or protein levels. To investigate whether HIF-1
      was involved in the hypoxia-mediated induction of TH, PC12 cells were exposed to
      hypoxia in the presence of the A(2)A receptor antagonist ZM241385, which
      prevented hypoxia-dependent TH induction despite HIF-1 activation; in line with
      this finding, the inhibition of HIF-1 did not abolish TH induction in hypoxic
      PC12 cells. These results indicate that, under hypoxic conditions, TH (a key
      factor in systemic adaptation to reduced oxygen availability) is not regulated by
      HIF-1, the primary modulator of the response to hypoxia, but by the adenosine
      A(2)A receptor-mediated signalling pathway.

PMID- 20143410
TI  - Direct asymmetric Michael addition of thioether-based aryl sulfanyl-propan-2-one
      to nitroalkenes catalyzed by a chiral amine-thiourea bifunctional organocatalyst.
AB  - Although the organocatalytic direct asymmetric Michael reactions of carbonyl
      compounds to nitroalkenes have been investigated intensely, the Michael reaction
      of the thioether-based donors remains a rather undeveloped field. This work
      concerns the asymmetric Michael addition of aryl sulfanyl-propan-2-one to
      nitroalkenes with benzoic acid as an additive, and chiral amine-thiourea as a
      bifunctional organocatalyst. The reactions provided the highly functionalized
      chiral adducts with excellent enantioselectivities (up to 96% ee) and good
      yields. Moreover, the further transformed products exhibited excellent
      diastereoselectivity.

PMID- 20143409
TI  - Transgenic mouse and cell culture models demonstrate a lack of mechanistic
      connection between endoplasmic reticulum stress and tau dysfunction.
AB  - In vivo aggregation of tau protein is a hallmark of many neurodegenerative
      disorders, including Alzheimer's disease (AD). Recent evidence has also
      demonstrated activation of the unfolded protein response (UPR), a cellular
      response to endoplasmic reticulum (ER) stress, in AD, although the role of the
      UPR in disease pathogenesis is not known. Here, three model systems were used to
      determine whether a direct mechanistic link could be demonstrated between tau
      aggregation and the UPR. The first model system used was SH-SY5Y cells, a
      neuronal cultured cell line that endogenously expresses tau. In this system, the
      UPR was activated using chemical stressors, tunicamycin and thapsigargin, but no
      changes in tau expression levels, solubility, or phosphorylation were observed.
      In the second model system, wild-type 4R tau and P301L tau, a variant with
      increased aggregation propensity, were heterologously overexpressed in HEK 293
      cells. This overexpression did not activate the UPR. The last model system
      examined here was the PS19 transgenic mouse model. Although PS19 mice, which
      express the P301S variant of tau, display severe neurodegeneration and formation
      of tau aggregates, brain tissue samples did not show any activation of the UPR.
      Taken together, the results from these three model systems suggest that a direct
      mechanistic link does not exist between tau aggregation and the UPR.

PMID- 20143411
TI  - Chiral discrimination in diastereomeric salts of chlorine-substituted mandelic
      acid and phenylethylamine.
AB  - The crystal structures of diastereomeric salts of chloromandelic acid and
      phenylethylamine were determined and are presented herein. The structure
      comparison between less soluble salts and more soluble salts shows that weak
      interactions such as CH/pi interactions and van der Waals gain importance and
      contribute to chiral recognition when the hydrogen bonding patterns are very
      similar.

PMID- 20143412
TI  - Enantioselective synthesis and antioxidant activity of 3-(3,4-dihydroxyphenyl)
      glyceric acid--basic monomeric moiety of a biologically active polyether from
      Symphytum asperum and S. caucasicum.
AB  - The racemic and enantioselective synthesis of a novel glyceric acid derivative,
      namely, 2,3-dihydroxy-3-(3,4-dihydroxyphenyl)-propionic acid as well as the
      antioxidant activities is described. The virtually pure enantiomers, (+)-(2R,3S)
      2,3-dihydroxy-3-(3,4-dihydroxyphenyl)-propionic acid and (-)-(2S,3R)-2,3
      dihydroxy-3-(3,4-dihydroxyphenyl)-propionic acid were synthesized for the first
      time via Sharpless asymmetric dihydroxylation of trans-caffeic acid derivatives
      using the enantiocomplementary catalysts, (DHQD)(2)-PHAL and (DHQ)(2)-PHAL. The
      determination of enantiomeric purity of the novel chiral glyceric acid
      derivatives was performed by high-performance liquid chromatographic techniques
      on the stage of their alkylated precursors. The novel glyceric acid derivatives
      show strong antioxidant activity against hypochlorite and N,N-diphenyl-N-picryl
      hydrazyl free radical. Their antioxidant activity is about 40-fold higher than
      that of the corresponding natural polyether and three-fold higher of trans
      caffeic acid itself.

PMID- 20143413
TI  - Determination of catechin diastereomers from the leaves of Byrsonima species
      using chiral HPLC-PAD-CD.
AB  - When catechins are found in plant extracts, they are almost always identified as
      catechin and/or epicatechin probably due to stereoselectivity of the enzymes
      involved in the biosynthesis of these substances. However, the lack of reports
      regarding to ent-catechin as well as ent-epicatechin does not necessarily mean
      that these compounds have not been produced. In fact, most of the previous
      reports used chromatographic conditions not suitable for such separation. This
      article describes a simple and reliable analytical HPLC-PAD-CD method for
      simultaneous determination of catechin diastereomers both in infusions and
      extracts from the leaves of Byrsonima species. The direct separation of catechin,
      ent-catechin, epicatechin, and ent-epicatechin was obtained in normal phase by
      HPLC-PAD-CD using Chiralcel OD-H as chiral stationary phase and n-hexane/ethanol
      with 0.1% of TFA as mobile phase.

PMID- 20143414
TI  - Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced
      cerebral edema.
AB  - Neonatal hypoxia/ischemia (HI) is a common cause of cognitive and behavioral
      deficits in children with hyperoxia treatment (HHI) being the current therapy for
      newborn resuscitation. HI induces cerebral edema that is associated with poor
      neurological outcomes. Our objective was to characterize cerebral edema after HI
      and determine the consequences of HHI (40% or 100% O(2)). Dry weight analyses
      showed cerebral edema 1 to 21 days after HI in the ipsilateral cortex; and 3 to
      21 days after HI in the contralateral cortex. Furthermore, HI increased blood
      brain barrier (BBB) permeability 1 to 7 days after HI, leading to bilateral
      cortical vasogenic edema. HHI failed to prevent HI-induced increase in BBB
      permeability and edema development. At the molecular level, HI increased
      ipsilateral, but not contralateral, AQP4 cortical levels at 3 and up to 21 days
      after HI. HHI treatment did not further affect HI-induced changes in AQP4. In
      addition, we observed developmental increases of AQP4 accompanied by significant
      reduction in water content and increase permeability of the BBB. Our results
      suggest that the ipsilateral HI-induced increase in AQP4 may be beneficial and
      that its absence in the contralateral cortex may account for edema formation
      after HI. Finally, we showed that HI induced impaired motor coordination 21 days
      after the insult and HHI did not ameliorate this behavioral outcome. We conclude
      that HHI treatment is effective as a resuscitating therapy, but does not
      ameliorate HI-induced cerebral edema and impaired motor coordination.

PMID- 20143415
TI  - Determination of the absolute configurations of synthetic daunorubicin analogues
      using vibrational circular dichroism spectroscopy and density functional theory.
AB  - The absolute configurations of three synthesized anthracycline analogues have
      been determined using vibrational circular dichroism (VCD) spectroscopy and the
      density functional theory (DFT) calculations. The experimental VCD spectra of the
      three compounds have been measured for the first time in the film state, prepared
      from their CDCl(3) solutions. Conformational searches for the monomers and some
      dimers of the three compounds have been performed at the DFT level using the
      B3LYP functional and the 6-311G** and 6-311++G** basis sets. The corresponding
      vibrational absorption and VCD spectra have been calculated. The good agreement
      between the experimental and the calculated spectra allows one to assign the
      absolute configurations of the three compounds with high confidence. In addition,
      the dominant conformers of the three compounds have also been identified.

PMID- 20143416
TI  - A practical and efficient method for the resolution of 3-phospholene 1-oxides via
      coordination complex formation.
AB  - A simple, efficient, and economical method based on the combination of the
      exceptional behavior of o,o'-dibenzoyl- or o,o'-di-p-toluyl-(2R,3R)-tartaric acid
      in chiral recognition processes, and the coordination ability of calcium or
      magnesium ion was developed for the resolution of phospholene oxides 1. The
      calcium or magnesium salt of (-)-o,o'-dibenzoyl-(2R,3R)-tartaric acid 2,4-6 or
      calcium hydrogen (-)-o,o'-di-p-toluyl-(2R,3R)-tartrate 3 may form crystalline
      diastereomeric coordination complexes with the appropriate antipode of
      substituted 3-phospholene oxides 1 that makes possible efficient resolutions.
      Optically active phospholene oxides 1 were prepared directly by simply
      crystallization and digestion of the corresponding diastereomeric complexes so
      formed. Thermal behavior of the crystalline diastereomeric complexes was studied
      by simultaneous TG/DTA. The novel method may be of more general value in respect
      of the resolution of tertiary phosphine oxides.

PMID- 20143417
TI  - Special DSM-V issues on anxiety, obsessive-compulsive spectrum, posttraumatic,
      and dissociative disorders.

PMID- 20143419
TI  - Hexokinase II gene transfer protects against neurodegeneration in the rotenone
      and MPTP mouse models of Parkinson's disease.
AB  - A typical feature of Parkinson's disease is the progressive loss of dopaminergic
      neurons in the substantia nigra, in which inhibition of mitochondrial complex I
      activity may play an important role. Rotenone or 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) inhibit the mitochondrial complex I and they cause the
      death of substantia nigra dopaminergic neurons, thereby providing acute murine
      models of Parkinson's disease. We have found that increasing mitochondrial
      hexokinase II activity can prevent cell death in neuronal cultures treated with
      rotenone. As a result, we have studied the effects of hexokinase II gene transfer
      in vivo using a herpes simplex virus type 1 (HSV-1) amplicon vector. The placHK2
      amplicon vector was injected into substantia nigra of mice that were subsequently
      administered rotenone or MPTP. Overexpression of hexokinase II prevented both
      rotenone and MPTP-induced dopaminergic neuronal cell death, as well as reducing
      the associated motor defects. Our results provide the first proof-of-principle
      that hexokinase II protects against dopaminergic neurodegeneration in vivo,
      emphasizing the role of this enzyme in promoting neuronal survival. Thus, the
      increase of hexokinase II expression by gene transfer or other means represents a
      promising approach to treat Parkinson's and other neurodegenerative diseases.

PMID- 20143418
TI  - Incidence and prognostic impact of secondary cytogenetic aberrations in a series
      of 145 patients with mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with an aggressive
      behavior, characterized by the t(11;14)(q13;q32). Several secondary genetic
      abnormalities with a potential role in the oncogenic process have been described.
      Studies of large MCL series using conventional cytogenetics, and correlating with
      proliferation and survival, are scarce. We selected 145 MCL cases at diagnosis,
      displaying an aberrant karyotype, from centers belonging to the Spanish
      Cooperative Group for Hematological Cytogenetics. Histological subtype,
      proliferative index and survival data were ascertained. Combined cytogenetic and
      molecular analyses detected CCND1 translocations in all cases, mostly
      t(11;14)(q13;q32). Secondary aberrations were present in 58% of patients, the
      most frequent being deletions of 1p, 13q and 17p, 10p alterations and 3q gains.
      The most recurrent breakpoints were identified at 1p31-32, 1p21-22, 17p13, and
      1p36. Aggressive blastoid/pleomorphic variants displayed a higher karyotypic
      complexity, a higher frequency of 1p and 17p deletions and 10p alterations, a
      higher proliferation index and poor survival. Gains of 3q and 13q and 17p13
      losses were associated with reduced survival times. Interestingly, gains of 3q
      and 17p losses added prognostic significance to the morphology in a multivariate
      analysis. Our findings confirm previous observations indicating that
      proliferation index, morphology and several secondary genetic alterations (3q
      gains and 13q and 17p losses) have prognostic value in patients with MCL.
      Additionally, we observed that 3q gains and 17p losses detected by conventional
      cytogenetics are proliferation-independent prognostic markers indicating poor
      outcome.

PMID- 20143420
TI  - Down-expression of PGC-1alpha partially mediated by JNK/c-Jun through binding to
      CRE site during apoptotic procedure in cerebellar granule neurons.
AB  - In eukaryotes, mitochondria are critical for cellular bioenergetics and mediating
      apoptosis. The transcriptional coactivator peroxisome proliferator-activated
      receptor gamma coactivator 1alpha (PGC-1alpha) is an important regulator of
      mitochondrial biogenesis and function. However, the role of PGC-1alpha in
      neuronal apoptosis and its regulation by apoptotic pathway are still unknown. We
      demonstrated that PGC-1alpha expression was down-regulated in cerebellar granule
      neurons(CGNs) after activation of the JNK/c-Jun pathway by potassium deprivation.
      Overexpression of PGC-1alpha partially protected CGNs from potassium deprivation
      induced apoptosis. JNK-specific inhibitors, SP600125 and CEP11004, partially
      blocked the inhibitory effects of JNK on PGC-1alpha expression and its promoter
      activity. Furthermore, ChIP assays revealed that c-Jun was able to bind to the
      CRE site (-188 to -180) in the PGC-1alpha promoter. In conclusion, these results
      suggest that down-expression of PGC-1alpha partially mediated by activation of
      JNK/c-Jun may be through the binding of c-Jun to the CRE site in the PGC-1alpha
      promoter, and it might be involved in potassium deprivation-induced apoptosis in
      CGNs.

PMID- 20143421
TI  - Identification of novel 1,4-benzoxazine compounds that are protective in tissue
      culture and in vivo models of neurodegeneration.
AB  - Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and
      Huntington's disease and conditions such as ischemic stroke affect millions of
      individuals annually and exert an enormous financial burden on society. A
      hallmark of these conditions is the abnormal loss of neurons. Currently, there
      are no effective strategies to prevent neuronal death in these pathologies. We
      report that several 2-arylidine and 2-hetarylidin derivatives of the 1,4
      benzoxazines class of compounds are highly protective in tissue culture models of
      neurodegeneration. Results obtained using pharmcalogical inhibitors indicate that
      neuroprotection by these compounds does not involve the Raf-MEK-ERK or PI-3
      kinase-Akt signaling pathways nor other survival-promoting molecules such as
      protein kinase A (PKA), calcium calmodulin kinase A (CaMK), and histone
      deacetylases (HDACs). We tested one of these compounds, (Z)-6-amino-2-(3',5'
      dibromo-4'-hydroxybenzylidene)-2H-benzo[b][1,4]oxazin-3(4H)-one, designated as
      HSB-13, in the 3-nitropropionic acid (3-NP)-induced mouse model of Huntington's
      disease. HSB-13 reduced striatal degeneration and improved behavioral performance
      in mice administered with 3-NP. Furthermore, HSB-13 was protective in a
      Drosophila model of amyloid precursor protein (APP) toxicity. To understand how
      HSB-13 and other 1,4-benzoxazines protect neurons, we performed kinase profiling
      analyses. These analyses showed that HSB-13 inhibits GSK3, p38 MAPK, and cyclin
      dependent kinases (CDKs). In comparison, another compound, called ASK-2a, that
      protects cerebellar granule neurons against low-potassium-induced death inhibits
      GSK3 and p38 MAPK but not CDKs. Despite its structural similarity to HSB-13,
      however, ASK-2a is incapable of protecting cortical neurons and HT22 cells
      against homocysteic acid (HCA)-induced or Abeta toxicity, suggesting that
      protection against HCA and Abeta depends on CDK inhibition. Compounds described
      in this study represent a novel therapeutic tool in the treatment of
      neurodegenerative diseases.

PMID- 20143422
TI  - Nerve growth factor-evoked nociceptor sensitization in pig skin in vivo.
AB  - Peripheral sensitization of skin nociceptors by nerve growth factor (NGF) was
      explored in pig skin in vivo. As an objective output measure, the area of axon
      reflex-mediated erythema was assessed upon mechanical, thermal, chemical, and
      electrical stimuli delivered at 1, 3, and 7 days after i.d. injection of 1 microg
      NGF into the pig's back skin (n = 8). Pretreatment with NGF provoked a
      sensitization to mechanical (600 mN), thermal (10 sec 49 degrees C) and chemical
      (15 microl, pH 3) stimuli that lasted for 7 days. No sensitization, however, was
      found in response to weak mechanical (100 mN), weak thermal (10 sec 45 degrees
      C), or electrical stimuli. Irrespective of the skin pretreatment (NGF or PBS
      vehicle control), the area of electrically induced erythema decreased upon
      repetition (days 1-7) by 70% (P < 0.05). Sensitization of sensory endings by NGF
      upon mechanical, heat, and chemical stimuli suggests recruitment of sensory
      transducer molecules [e.g., TRPV1, acid-sensing ion channels (ASICs)]. In
      contrast, the gradual decrease in electrically induced erythema over 7 days might
      be attributable to axonal desensitization and possibly activity-dependent down
      regulation of sodium channels. Thus, long-lasting sensitization processes of
      nociceptor endings or axonal sodium channel desensitization mechanisms can be
      explored in the pig as a translational experimental animal model.

PMID- 20143423
TI  - More severe type 2 diabetes-associated ischemic stroke injury is alleviated in
      aldose reductase-deficient mice.
AB  - Aldose reductase (AR), the first enzyme in the polyol pathway, has been
      implicated in a wide variety of physiological and pathological functions, such as
      diabetic vascular and neural complications. It is known that diabetes mellitus
      can exacerbate brain and retina damage after ischemic injuries. However, the
      underlying mechanisms are not clear. In the present study, we made use of db/db
      mice with an AR null mutation (AR(-/-)db/db) to understand better the role of AR
      in the pathogenesis of brain and retina ischemic injuries under diabetic
      conditions. Cerebral and retinal ischemia was induced by transient middle
      cerebral artery occlusion in control and diabetic mice either with or without an
      AR null mutation. Mice were evaluated for neurological deficits after 30 min of
      ischemia and 23.5 hr of reperfusion. Our results showed that the diabetic db/db
      mice had significantly more severe neurological deficit and larger brain infarct
      size than the nondiabetic mice. Compared with wild-type db/db mice, the AR(-/
      )db/db mice had significantly lower neurological scores, smaller brain infarct
      areas, and less hemispheric brain swelling. Retinal swelling was also
      significantly decreased in the AR(-/-)db/db mice. Less swelling in the brain and
      retina of the AR(-/-)db/db mice correlated with less expression of the water
      channel aquaporin 4. Taken together, these data clearly show that deletion of AR
      leads to less severe brain and retinal ischemic injuries in the diabetic db/db
      mouse. The present study indicates that inhibition of AR in diabetics may protect
      against damage in the brain and retina following ischemic reperfusion injury.

PMID- 20143424
TI  - Local isoform-specific NOS inhibition: a promising approach to promote motor
      function recovery after nerve injury.
AB  - Physical injury to a nerve is the most frequent cause of acquired peripheral
      neuropathy, which is responsible for loss of motor, sensory and/or autonomic
      functions. Injured axons in the peripheral nervous system maintain the capacity
      to regenerate in adult mammals. However, after nerve transection, stumps of
      damaged nerves must be surgically joined to guide regenerating axons into the
      distal nerve stump. Even so, severe functional limitations persist after
      restorative surgery. Therefore, the identification of molecules that regulate
      degenerative and regenerative processes is indispensable in developing
      therapeutic tools to accelerate and improve functional recovery. Here, I consider
      the role of nitric oxide (NO) synthesized by the three major isoforms of NO
      synthases (NOS) in motor neuropathy. Neuronal NOS (nNOS) seems to be the primary
      source of NO that is detrimental to the survival of injured motoneurons.
      Endothelial NOS (eNOS) appears to be the major source of NO that interferes with
      axonal regrowth, at least soon after injury. Finally, NO derived from inducible
      NOS (iNOS) or nNOS is critical to the process of lipid breakdown for Wallerian
      degeneration and thereby benefits axonal regrowth. Specific inhibitors of these
      isoforms can be used to protect injured neurons from degeneration and promote
      axonal regeneration. A cautious proposal for the treatment of acquired motor
      neuropathy using therapeutic tools that locally interfere with eNOS/nNOS
      activities seems to merit consideration.

PMID- 20143425
TI  - Caspases-2 and -8 are involved in the presenilin1/gamma-secretase-dependent
      cleavage of amyloid precursor protein after the induction of apoptosis.
AB  - The presenilin/gamma-secretase protease cleaves many type-I membrane proteins,
      including the amyloid beta-protein (Abeta) precursor (APP). Previous studies have
      shown that apoptosis induces alterations in Abeta production in a caspase
      dependent manner. Here, we report that staurosporine (STS)-induced apoptosis
      induces caspase-8 and/or-2-dependent gamma-secretase activation. Blocking of
      caspase activity with caspase-8 inhibitor z-IETD-fmk, and caspase-2 inhibitor z
      VDVAD-fmk reduced Abeta production by STS in H4 cells expressing the Swedish
      mutant of APP (HSW) or APP-C99 (H4-C99). There was no inhibitory effect of other
      caspases (-1, -3, -5, -6, -9) on Abeta production by STS. This finding was
      further supported by evidence that siRNA transfection, depleting caspase-2 or -8
      levels, lowered Abeta production in HSW and H4-C99 cells without affecting
      expression of APP or gamma-secretase complex. In addition, Abeta production by
      STS was decreased by JNK inhibitors, SP600125. These results suggest that caspase
      2 and/or -8 is involved in presenilin/gamma-secretase activation and Abeta
      production in apoptosis.

PMID- 20143426
TI  - Agoraphobia: a review of the diagnostic classificatory position and criteria.
AB  - The status of agoraphobia (AG) as an independent diagnostic category is reviewed
      and preliminary options and recommendations for the fifth edition of The
      Diagnostic and Statistical Manual (DSM-V) are presented. The review concentrates
      on epidemiology, psychopathology, neurobiology, vulnerability and risk factors,
      clinical course and outcome, and correlates and consequences of AG since 1990.
      Differences and similarities across conventions and criteria of DSM and ICD-10
      are considered. Three core questions are addressed. First, what is the evidence
      for AG as a diagnosis independent of panic disorder? Second, should AG be
      conceptualized as a subordinate form of panic disorder (PD) as currently
      stipulated in DSM-IV-TR? Third, is there evidence for modifying or changing the
      current diagnostic criteria? We come to the conclusion that AG should be
      conceptualized as an independent disorder with more specific criteria rather than
      a subordinate, residual form of PD as currently stipulated in DSM-IV-TR. Among
      other issues, this conclusion was based on psychometric evaluations of the
      construct, epidemiological investigations which show that AG can exist
      independently of panic disorder, and the impact of agoraphobic avoidance upon
      clinical course and outcome. However, evidence from basic and clinic validation
      studies remains incomplete and partly contradictory. The apparent advantages of a
      more straightforward, simpler classification without implicit hierarchies and
      insufficiently supported differential diagnostic considerations, plus the option
      for improved further research, led to favoring the separate diagnostic criteria
      for AG as a diagnosis independent of panic disorder.

PMID- 20143427
TI  - Social anxiety disorder: questions and answers for the DSM-V.
AB  - BACKGROUND: This review evaluates the DSM-IV criteria of social anxiety disorder
      (SAD), with a focus on the generalized specifier and alternative specifiers, the
      considerable overlap between the DSM-IV diagnostic criteria for SAD and avoidant
      personality disorder, and developmental issues. METHOD: A literature review was
      conducted, using the validators provided by the DSM-V Spectrum Study Group. This
      review presents a number of options and preliminary recommendations to be
      considered for DSM-V. RESULTS/CONCLUSIONS: Little supporting evidence was found
      for the current specifier, generalized SAD. Rather, the symptoms of individuals
      with SAD appear to fall along a continuum of severity based on the number of
      fears. Available evidence suggested the utility of a specifier indicating a
      "predominantly performance" variety of SAD. A specifier based on "fear of showing
      anxiety symptoms" (e.g., blushing) was considered. However, a tendency to show
      anxiety symptoms is a core fear in SAD, similar to acting or appearing in a
      certain way. More research is needed before considering subtyping SAD based on
      core fears. SAD was found to be a valid diagnosis in children and adolescents.
      Selective mutism could be considered in part as a young child's avoidance
      response to social fears. Pervasive test anxiety may belong not only to SAD, but
      also to generalized anxiety disorder. The data are equivocal regarding whether to
      consider avoidant personality disorder simply a severe form of SAD. Secondary
      data analyses, field trials, and validity tests are needed to investigate the
      recommendations and options.

PMID- 20143428
TI  - Impaired fear inhibition is a biomarker of PTSD but not depression.
AB  - BACKGROUND: A central problem in posttraumatic stress disorder (PTSD) is a
      reduced capacity to suppress fear under safe conditions. Previously, we have
      shown that combat-related PTSD patients have impaired inhibition of fear
      potentiated startle (FPS). Given the high comorbidity between PTSD and
      depression, our goal was to see whether this impairment is specific to PTSD, or a
      non-specific symptom associated with both disorders. METHODS: Fear-potentiated
      startle was assessed in 106 trauma-exposed individuals divided into four groups:
      (a) No diagnosis control, (b) PTSD only, (c) major depression (MDD) only, and (d)
      comorbid PTSD and MDD. We used a novel conditional discrimination procedure, in
      which one set of shapes (the danger signal) was paired with aversive airblasts to
      the throat, and different shapes (the safety signal) were presented without
      airblasts. The paradigm also included fear inhibition transfer test. RESULTS:
      Subjects with comorbid MDD and PTSD had higher FPS to the safety signal and to
      the transfer test compared to controls and MDD only subjects. In contrast to the
      control and MDD groups, the PTSD and comorbid PTSD and MDD groups did not show
      fear inhibition to safety cues. CONCLUSIONS: These results suggest that impaired
      fear inhibition may be a specific biomarker of PTSD symptoms.

PMID- 20143429
TI  - Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate
      cancer.
AB  - BACKGROUND: : A study was conducted to determine the 5-year recurrence-free
      survival in patients with high-risk prostate cancer after neoadjuvant combination
      chemotherapy followed by surgery. Secondary endpoints included safety, pathologic
      effects of chemotherapy, and predictors of disease recurrence. METHODS: : Fifty
      seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m(2)
      and escalating mitoxantrone to 4 mg/m(2) before prostatectomy. Patients were
      treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week
      schedule. A tissue microarray, constructed from the prostatectomy specimens,
      served to facilitate the exploratory evaluation of biomarkers. The primary
      endpoint was recurrence-free survival. Disease recurrence was defined as a
      confirmed serum prostate-specific antigen (PSA) >0.4 ng/mL. RESULTS: : Of the 57
      patients, 54 received 4 cycles of docetaxel and mitoxantrone before radical
      prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and
      hyperglycemia. Serum testosterone levels remained stable after chemotherapy.
      Negative surgical margins were attained in 67% of cases. Lymph node involvement
      was detected in 18.5% of cases. With a median follow-up of 63 months, 27 of 57
      (47.4%) patients recurred. The Kaplan-Meier recurrence-free survival at 2 years
      was 65.5% (95% confidence interval [CI], 53.0%-78.0%) and was 49.8% at 5 years
      (95% CI, 35.5%-64.1%). Pretreatment serum PSA, lymph node involvement, and
      postchemotherapy tissue vascular endothelial growth factor expression were
      independent predictors of early recurrence. CONCLUSIONS: : Preoperative
      chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of
      the high-risk patients remain free of disease recurrence at 5 years, and clinical
      and molecular predictors of early recurrence were identified. Cancer 2010. (c)
      2010 American Cancer Society.

PMID- 20143430
TI  - Differential methylation of cell-free circulating DNA among patients with
      pancreatic cancer versus chronic pancreatitis.
AB  - BACKGROUND: : Although patients with chronic pancreatitis (CP) have an increased
      risk of pancreatic cancer (PanCa), the timely detection of PanCa often is
      difficult, because the symptoms of CP and PanCa are very similar. Moreover,
      secondary inflammation may be identified in PanCa, further complicating
      diagnosis. To improve the survival of patients with PanCa, a reliable test to
      differentiate CP from PanCa is needed. In this article, the authors describe a
      methylation profile of cell-free plasma DNA that distinguished CP from PanCa with
      >90% accuracy. METHODS: : Methylation in cell-free, plasma DNA was compared among
      30 samples from patients with CP, 30 samples from patients with PanCa, and 30
      samples from healthy controls (N) using a microarray-mediated methylation
      analysis of 56 fragments in each sample (MethDet56). Statistical analysis was
      done by using the Fisher exact test, a naive Bayes algorithm, and 25 rounds of 5
      fold cross-validation. RESULTS: : The MethDet56 methylation analysis technique
      identified 17 gene promoters as informative (8 for distinguishing N from CP and
      14 for distinguishing CP from PanCa). It achieved 81.7% sensitivity and 78%
      specificity (P<.01) in the detection of CP (N vs CP) and 91.2% sensitivity and
      90.8% specificity (P<.01) in the differential detection of PanCa (PanCa vs CP).
      CONCLUSIONS: : The current data suggested that, among patients with pancreatic
      disease, the methylation profiles of inflammatory disease and cancer are
      different and open a new venue for the development of biomarkers for differential
      diagnosis. Further investigation of diagnostic biomarkers for pancreatic cancer
      based on methylation in cell-free, circulating DNA appears to be warranted.
      Cancer 2010. (c) 2010 American Cancer Society.

PMID- 20143431
TI  - Trimodality therapy without a platinum compound for localized carcinoma of the
      esophagus and gastroesophageal junction.
AB  - BACKGROUND: : The use of platinum-based chemoradiation for esophageal cancer is
      routine, but it is unclear which class of cytotoxic are optimum. It was
      hypothesized that chemoradiotherapy with fluoropyrimidine, taxane, and
      camptothecin would have preserved or improved efficacy with no compromise in
      safety. METHODS: : Patients with histologically confirmed, resectable esophageal
      carcinoma were eligible. In addition to other tests, a baseline endoscopic
      ultrasonography (EUS) was obtained. Patients were medically fit and had near
      normal organ functions. Patients received docetaxel and irinotecan, plus 5
      fluorouracil as induction therapy and then the same cytotoxics with 50.4 grays of
      radiotherapy followed by an attempted surgery. Pathologic complete response
      (pathCR) at a rate of > or =20% was the primary endpoint. The pathCR and R0
      resection were correlated with overall survival (OS). Safety was documented.
      RESULTS: : Fifty-five patients were enrolled. Seven were women, and the median
      age was 56 years. Fifty-three (96%) patients had EUST3, and 41 (75%) had EUSN1
      disease. Forty-three (78%) patients underwent surgery, 20% achieved a pathCR, and
      76.4% underwent an R0 resection. The median survival (n = 55 patients) was 43.3
      months (range, 19-75 months). Baseline clinical parameters were not found to be
      predictive of OS; however, patients with a pathCR (P = .005) and who underwent R0
      resection (P < or = .0001) had an improved OS. There was 1 treatment-related
      postsurgical death reported. Grade 3 or 4 toxicity (graded according to the
      National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in
      62% of patients. CONCLUSIONS: : The results of the current study documented that
      this 3-drug, noncisplatin-based chemoradiotherapy was feasible, safe, and active
      but not better than the published cisplatin-based chemoradiotherapy. A
      fluoropyrimidine and another cytotoxic (from any class) may be adequate to
      establish a baseline chemoradiotherapy regimen to combine biologics. Cancer 2010.
      (c) 2010 American Cancer Society.

PMID- 20143432
TI  - Progress for resectable pancreatic [corrected] cancer?: a population-based
      assessment of US practices.
AB  - BACKGROUND: : Pancreatic adenocarcinoma is a deadly disease; however, recent
      studies have suggested improved outcomes in patients with locoregional cancer.
      Progress was evaluated at a national level in resected patients, as measured by
      the proportion who received guideline-directed treatment and trends in survival.
      METHODS: : The linked Surveillance, Epidemiology, and End Results and Medicare
      databases were queried to identify resections for pancreatic adenocarcinoma
      performed between 1991 and 2002. Receipt and timing of chemotherapy and radiation
      with respect to time-trend were assessed. Using logistic regression, factors
      associated with adjuvant combination chemoradiotherapy were identified. Kaplan
      Meier curves stratified by year and treatment were used to assess survival.
      RESULTS: : Of the 1910 patients, 47.9% (n = 915) received some form of adjuvant
      therapy within the first 6 months postoperatively; 34.4% (n = 658) received
      combination chemoradiotherapy (chemoRT). ChemoRT demonstrated a significant
      increase, from 29.2% to 37.5% (P < .0001). Neoadjuvant therapy was used in 5.7%
      (n = 108) of patients; no trend was observed during the study (P = .1275). The in
      hospital mortality rate was 8.0% (n = 153 patients); no significant trend was
      noted (P = .3116). Kaplan-Meier survival, stratified by year group of diagnosis,
      did not change significantly over time (log-rank test, P = .4381), even with
      comparisons of the first 3 years with the last 3 years of the study (log-rank
      test, P = .3579). CONCLUSIONS: : Adherence to guideline-directed care isimproving
      in the United States; however, the pace is slow, and overall survival has yet to
      be impacted significantly. Both increased use of adjuvant therapy and the
      development of more promising systemic treatments are necessary to improve
      survival for patients with resectable pancreatic cancer. Cancer 2010. (c) 2010
      American Cancer Society.

PMID- 20143433
TI  - In-hospital mortality from liver resection for hepatocellular carcinoma: a simple
      risk score.
AB  - BACKGROUND: : There is a wide spectrum of disease burden in hepatocellular
      carcinoma accompanied by several options for surgical management. However, the
      associated mortality of such procedures is not well defined. Accurate predictions
      of patients' perioperative risk would be helpful to guide decision making.
      METHODS: : The Nationwide Inpatient Sample was queried for data from 1998 to
      2005. A cohort of patients who were discharged for hepatic procedures with a
      diagnosis of primary liver neoplasm was assembled. Procedures were categorized as
      hepatic lobectomy, wedge resection, or enucleation/ablation. Logistic regression
      and bootstrap methods were used to create an integer risk score for estimating
      the risk of in-hospital mortality using procedure type, patient demographics,
      comorbidities, and hospital type. A randomly selected sample of 80% of the cohort
      (n = 2263) was used to create the score with validation conducted in the
      remaining 20% (n = 571). RESULTS: : In total, 2834 patient discharges were
      identified. Overall in-hospital mortality was 6.52%. Factors that were included
      in the final model were age, sex, Charlson comorbidity score, procedure type, and
      teaching hospital status. Integer values were assigned to these characteristics
      and were used to calculate an additive score. Four clinically relevant score
      groups were assembled to stratify the risk of in-hospital mortality, with a 19
      fold gradient of mortality that ranged from 1.5% to 28.3%. In the derivation set,
      as in the validation set, the score discriminated well with c-statistics of 0.75
      and 0.73, respectively. CONCLUSIONS: : The current results indicated that an
      integer-based risk score can be used to predict in-hospital mortality after
      surgery for hepatocellular carcinoma, and it may be useful for preoperative risk
      stratification and patient counseling. Cancer 2010. (c) 2010 American Cancer
      Society.

PMID- 20143434
TI  - Single-institution experience with ipilimumab in advanced melanoma patients in
      the compassionate use setting: lymphocyte count after 2 doses correlates with
      survival.
AB  - BACKGROUND: : Ipilimumab is a monoclonal antibody that antagonizes cytotoxic T
      lymphocyte antigen-4, a negative regulator of the immune system. The authors
      report on advanced refractory melanoma patients treated in a compassionate use
      trial of ipilimumab at the Memorial Sloan-Kettering Cancer Center. METHODS: :
      Patients with advanced refractory melanoma were treated in a compassionate use
      trial with ipilimumab 10 mg/kg every 3 weeks for 4 doses. Those with evidence of
      clinical benefit at Week 24 (complete response [CR], partial response [PR], or
      stable disease [SD]) then received ipilimumab every 12 weeks. RESULTS: : A total
      of 53 patients were enrolled, with 51 evaluable. Grade 3/4 immune-related adverse
      events were noted in 29% of patients, with the most common immune-related adverse
      events being pruritus (43%), rash (37%), and diarrhea (33%). On the basis of
      immune-related response criteria, the response rate (CR + PR) was 12% (95%
      confidence interval [CI], 5%-25%), whereas 29% had SD (95% CI, 18%-44%). The
      median progression-free survival was 2.6 months (95% CI, 2.3-5.2 months), whereas
      the median overall survival (OS) was 7.2 months (95% CI, 4.0-13.3 months).
      Patients with an absolute lymphocyte count (ALC) > micro =1000/microL after 2
      ipilimumab treatments (Week 7) had a significantly improved clinical benefit rate
      (51% vs 0%; P = .01) and median OS (11.9 vs 1.4 months; P < .001) compared with
      those with an ALC <1000/microL. CONCLUSIONS: : The results confirm that
      ipilimumab is clinically active in patients with advanced refractory melanoma.
      The ALC after 2 ipilimumab treatments appears to correlate with clinical benefit
      and OS, and should be prospectively validated. Cancer 2010. (c) 2010 American
      Cancer Society.

PMID- 20143435
TI  - Health anxiety and fear of fear in panic disorder and agoraphobia vs. social
      phobia: a prospective longitudinal study.
AB  - BACKGROUND: This study is aimed to evaluate the role of two vulnerability
      factors, health anxiety and fear of fear, in the prediction of the onset of panic
      disorder/agoraphobia (PDA) relative to a comparison anxiety disorder. METHODS:
      Young women, aged between 18 and 24 years, were investigated at baseline and, 17
      months later, using the Anxiety Disorders Interview Schedule-Lifetime and
      measures of health anxiety and fear of bodily sensations (subscale disease phobia
      of the Whiteley Index, and total score of the Body Sensations Questionnaire).
      First, 22 women with current PDA were compared to 81 women with current social
      phobia and 1,283 controls. Second, 24 women with an incidence of PDA were
      compared to 60 women with an incidence of social phobia and 1,036 controls.
      RESULTS: Multiple logistic regression analyses adjusted for history of physical
      diseases, somatic symptoms, and other psychological disorders revealed that (a)
      fear of bodily sensations was elevated for women with PDA vs. controls as well as
      women with social phobia, and (b) health anxiety (and history of physical
      diseases) was elevated in women who developed PDA vs. controls and vs. women who
      developed social phobia. CONCLUSIONS: These results suggest that health anxiety,
      as well as history of physical diseases, may be specific vulnerability factors
      for the onset of PDA relative to social phobia. Whereas fear of bodily sensations
      was not found to be a risk factor for the onset of panic disorder/agoraphobia, it
      was a specific marker of existing PDA relative to social phobia.

PMID- 20143436
TI  - The use of anticoagulants improves biochemical control of localized prostate
      cancer treated with radiotherapy.
AB  - BACKGROUND: : Substantial experimental evidence suggests that anticoagulants
      (ACs) may inhibit cancer growth and metastasis, although the limited data from
      clinical trials have been inconsistent. The potential antineoplastic effect of
      ACs was investigated in patients who received radiotherapy for localized prostate
      cancer. METHODS: : The study cohort consisted of 662 patients with adenocarcinoma
      of the prostate who received radiotherapy (RT) with curative intent. Among those
      622 men, 243 (37%) were receiving ACs (warfarin, clopidogrel, and/or aspirin).
      All patients received external-beam RT, permanent seed implantation, or a
      combination of both. Prostate-specific antigen (PSA) values were monitored for
      biochemical control of disease. RESULTS: : At a median follow-up of 49 months,
      the biochemical control rate at 4-years was significantly better in patients who
      received ACs at 91% compared with 78% in patients who did not receive ACs (P =
      .0002). The distant metastasis rate at 4 years also was reduced in the AC group
      compared with the non-AC group (1% vs 5%; P = .0248). In subgroup analysis, the
      improvement in biochemical control was significant only for patients with high
      risk disease. Along with Gleason score, T classification, and initial PSA, the
      use of AC therapy was associated independently with improved biochemical control
      in multivariate analysis. CONCLUSIONS: : AC therapy was associated with an
      improvement in biochemical control in patients with prostate cancer who received
      RT with curative intent. The effect was most prominent in patients who had high
      risk disease. Cancer 2010. (c) 2010 American Cancer Society.

PMID- 20143437
TI  - Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor
      for malignant melanoma.
AB  - BACKGROUND: : Melanoma tends to be refractory to various immunotherapies because
      of tumor-induced immunosuppression. To investigate the mechanism underlining the
      immunosuppression of melanoma patients, the authors focused on programmed cell
      death-1 (PD-1)/PD-1 ligand 1 (PD-L1) interaction between tumor cells and T cells.
      METHODS: : Melanoma specimens were collected from 59 primary tumors, 16 lymph
      nodes, and 4 lesions of in-transit metastasis. Specimens stained with anti-PD-L1
      monoclonal antibodies were digitalized to jpg files. To evaluate the intensity of
      PD-L1 expression, histograms were used, and the red density (RD) was measured. PD
      1 expression on T cells was analyzed in blood samples from 10 patients who had
      stage IV melanoma and in 4 samples of in-transit metastases. RESULTS: : Twenty
      five patients comprised the "low" PD-L1 expression group (RD value, <90), and 34
      patients comprised the "high" group (RD value, > or =90). Breslow tumor thickness
      in the high-expression group was significantly higher than in the low-expression
      group. Univariate and multivariate analyses revealed that the overall survival
      rate of the high-expression group was significantly lower than that of the low
      expression group. In all patients with stage IV disease who were examined, both
      CD8-positive and CD4-positive T cells had significantly higher PD-1 expression
      levels in the peripheral blood. Tumor-infiltrating T cells expressed high levels
      of PD-1, and its expression was elevated further during the clinical course.
      CONCLUSIONS: : The current results indicated that there is a correlation between
      the degree of PD-L1 expression and the vertical growth of primary tumors in
      melanoma. Multivariate analysis demonstrated that PD-L1 expression is an
      independent prognostic factor for melanoma. Cancer 2010. (c) 2010 American Cancer
      Society.

PMID- 20143438
TI  - Phase 2 trial of talampanel, a glutamate receptor inhibitor, for adults with
      recurrent malignant gliomas.
AB  - BACKGROUND: : Glioma cells secrete glutamate and also express alpha-amino-3
      hydroxy-5 methyl-4-isoxazolepropionate (AMPA) glutamate receptors, which
      contribute to the proliferation, migration, and neurotoxicity of malignant
      gliomas. Talampanel is an oral AMPA receptor inhibitor with excellent central
      nervous system penetration and good tolerability in clinical trials for epilepsy
      and other neurologic disorders. METHODS: : A phase 2 trial was conducted to
      evaluate the efficacy of talampanel in patients with recurrent malignant glioma
      as measured by 6-month progression-free survival (PFS6). RESULTS: : Thirty
      patients (22 with glioblastomas [GBMs] and 8 with anaplastic gliomas [AGs]; 63%
      men) with median age of 51 years (range, 20-67 years) and a median Karnofsky
      performance scale of 80 were included. Patients tolerated treatment well, and
      most adverse events were mild and reversible; the most common toxicities were
      fatigue (27%), dizziness (23%), and ataxia (17%). There was only 1 partial
      response (5%) reported in the GBM stratum and none among AG patients. At a median
      follow-up of 13 months, 28 patients (93%) had died. The PFS6 was 4.6% for the
      initial 22 GBM patients, and the study was terminated early due to treatment
      futility; the PFS6 was 0% for 8 AG patients. The median PFS was 5.9 weeks for GBM
      and 8.9 weeks for AG patients. The median overall survival was 13 weeks for GBM
      patients and 14 months for AG patients. CONCLUSIONS: : Talampanel was well
      tolerated but had no significant activity as a single agent in unselected
      recurrent malignant gliomas. Cancer 2010. Published 2010 by the American Cancer
      Society.

PMID- 20143439
TI  - Effectiveness of a patient- and practice-level colorectal cancer screening
      intervention in health plan members: design and baseline findings of the CHOICE
      trial.
AB  - BACKGROUND: : Evidence-based interventions have been found effective in
      increasing colorectal cancer (CRC) screening. Translating these successful
      interventions into real world settings, such as health plans, can be challenging.
      METHODS: : CHOICE (Communicating Health Options through Information and Cancer
      Education) is a controlled trial to test the effectiveness of a patient- and
      practice-level intervention to increase use of recommended CRC screening tests.
      The patient-level intervention was a patient decision aid and stage-targeted
      brochures, mailed to eligible health plan members, to provide information about
      CRC, available screening tests, and how to obtain CRC screening at their
      physicians' practices. The practice-level intervention was academic detailing to
      prepare practices to facilitate CRC testing once the patient was activated by the
      decision aid. Surveys and claims data will be used to assess CRC screening test
      completion. RESULTS: : Thirty-two primary care practices in Florida and Georgia
      participated. The authors recruited 443 participating health plan members for the
      trial; 211 were patients in intervention practices, and 232 were in usual care
      practices. Study participants reflected an insured population; the majority were
      white and aged <60 years. The authors also mailed the intervention to 343 people
      from intervention practices who did not respond to the eligibility or baseline
      survey. Receipt of screening in that group will be compared with screening among
      319 people from usual care practices who did not respond to these surveys using
      claims data. CONCLUSIONS: : The CHOICE study will demonstrate the effect of 2
      combined evidence-based interventions on CRC screening test completion among
      health plan members. Cancer 2010. (c) 2010 American Cancer Society.

PMID- 20143440
TI  - The impact of breast reconstruction on the delivery of chemotherapy.
AB  - BACKGROUND: : The purpose of this study was to evaluate the impact of
      postmastectomy breast reconstruction on the timing of chemotherapy. METHODS: :
      The authors included stage I-III breast cancer patients from 8 National
      Comprehensive Cancer Network institutions for whom guidelines recommended
      chemotherapy. Surgery type was categorized as breast-conserving surgery (BCS),
      mastectomy alone, mastectomy with immediate reconstruction (M + IR), or
      mastectomy with delayed reconstruction (M + DR). A Cox regression analysis was
      used to assess the association between surgery type and timing of chemotherapy
      initiation. RESULTS: : Of the 3643 patients, only 5.1% received it > or =8 weeks
      from surgery. In the multivariate analysis, higher stage, Caucasian and Hispanic
      race/ethnicity, lower body mass index, and absence of comorbid conditions were
      all significantly associated with earlier time to chemotherapy. There was also
      significant interaction among age, surgery, and chemotherapy delivery. Among
      women <60, time to chemotherapy was shorter for all surgery types compared with M
      + IR (statistical significant for all surgery types in the youngest age group and
      for BCS in women 40 to <50 years old). In contrast, among women > or =60, time to
      chemotherapy was shorter among women receiving M + IR or M + DR compared with
      those undergoing BCS or mastectomy alone, a difference that was statistically
      significant for the M + IR versus BCS comparison. CONCLUSIONS: : Immediate
      postmastectomy breast reconstruction does not appear to lead to omission of
      chemotherapy, but it is associated with a modest, but statistically significant,
      delay in initiating treatment. For most, it is unlikely that this delay has any
      clinical significance. Cancer 2010. (c) 2010 American Cancer Society.

PMID- 20143441
TI  - Racial and insurance disparities in the receipt of transplant among patients with
      hepatocellular carcinoma.
AB  - BACKGROUND: : Patients with hepatocellular carcinoma (HCC) have a poor prognosis
      if their tumors are not diagnosed early. The authors investigated factors
      associated with the receipt of liver transplant among patients with HCC and
      evaluated the effects of these differences on survival. METHODS: : The authors
      reviewed records from consecutive patients diagnosed with HCC at Columbia
      University Medical Center from January 1, 2002 to September 1, 2008. We compared
      patient clinical and demographic characteristics, developed a multivariable
      logistic regression model of predictors of transplant, and used a Cox model to
      analyze predictors of mortality. RESULTS: : Of 462 HCC patients, 175 (38%)
      received a transplant. Black patients were much less likely than whites to
      receive a transplant (odds ratio [OR], 0.03; 95% confidence interval [CI], 0.0
      0.37). Hispanics and Asians were also less likely to undergo transplantation, but
      the differences were not statistically significant. Patients with private
      insurance were more likely to receive a transplant than those with Medicaid (odds
      ratio [OR], 22.07; 95% confidence interval [CI], 2.67-182.34). Black and Hispanic
      patients, and Medicaid recipients, presented with more advanced disease than
      whites and privately insured patients, and had poorer survival. In a Cox model,
      those who did not receive a transplant were 3 times as likely as transplant
      recipients to die, but race and insurance were not independently predictive of
      mortality. CONCLUSIONS: : Race and insurance status were strongly associated with
      receipt of transplantation and with more advanced disease at diagnosis, but
      transplantation was the most important determinant of survival. Improved access
      to care for nonwhite and Medicaid patients may allow more patients to benefit
      from transplant. Cancer 2010. (c) 2010 American Cancer Society.

PMID- 20143442
TI  - Tumor progression by immune evasion in melanoma: role of the programmed cell
      death-1/programmed cell death-1 ligand 1 interaction.

PMID- 20143443
TI  - Inhibition of tumor growth and angiogenesis by a lysophosphatidic acid antagonist
      in an engineered three-dimensional lung cancer xenograft model.
AB  - BACKGROUND: : We developed an engineered three-dimensional (3D) tumor xenograft
      model of nonsmall cell lung cancer (NSCLC) in nude mice, and we used this model
      to evaluate a dual-activity inhibitor of lysophosphatidic acid (LPA) biosynthesis
      and receptor activation. METHODS: : First, BrP-LPA, a pan-antagonist for 4 LPA
      receptors and inhibitor of the lyosphospholipase D activity of autotaxin, was
      examined for inhibition of cell migration and cell invasion by human NSCLC A549
      cells. Second, A549 cells were encapsulated in 3D in 3 semisynthetic
      extracellular matrices (ECMs) based on chemically modified glycosaminoglycans,
      and injected subcutaneously in nude mice. Tumor volume and vascularity were
      determined as a function of semisynthetic ECMs composition. Third, engineered
      NSCLC xenografts were formed from A549 cells in either Extracel-HP or Matrigel,
      and mice were treated with 4 intraperitoneal injections of 3 mg/kg of BrP-LPA.
      RESULTS: : First, BrP-LPA inhibited cell migration and invasiveness of A549 cells
      in vitro. Second, tumor growth and microvessel formation for 3D encapsulated A549
      cells in vivo in nude mice increased in the following order: buffer only <
      Extracel < Extracel-HP < Extracel-HP containing growth factorss plus laminin.
      Third, tumor volumes increased rapidly in both Matrigel and Extracel-HP
      encapsulated A549 cells, and tumor growth was markedly inhibited by BrP-LPA
      treatment. Finally, tumor vascularization was dramatically reduced in the A549
      tumors treated with BrP-LPA. CONCLUSIONS: : Engineered A549 lung tumors can be
      created by 3D encapsulation in an ECM substitute with user controlled
      composition. The engineered tumors regress and lose vascularity in response to a
      dual activity inhibitor of the LPA signaling pathway. Cancer 2010. (c) 2010
      American Cancer Society.

PMID- 20143444
TI  - Reduced incidence of infusion-related reactions in metastatic colorectal cancer
      during treatment with cetuximab plus irinotecan with combined corticosteroid and
      antihistamine premedication.
AB  - BACKGROUND: : The multinational MABEL study of 1147 patients with metastatic
      colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen
      confirmed in a community practice setting the efficacy and safety of cetuximab
      combined with irinotecan. METHODS: : This report describes a post hoc analysis of
      the influence of prophylactic premedication on the incidence of infusion-related
      reactions (IRRs) in the MABEL study. The analysis was focused on the
      subpopulation of patients premedicated with antihistamines either with (n = 700)
      or without (n = 422) corticosteroids. Stepwise Cox regression modeling was used
      to examine the explanatory value of the type of premedication on progression-free
      survival (PFS) and overall survival (OS) times. RESULTS: : The incidence of IRRs
      was lower in the group of patients who received antihistamine plus corticosteroid
      (9.6%) compared with those who received antihistamine alone (25.6%). A similar
      trend was seen for grade 3 or 4 IRRs (1.0% vs 4.7%, respectively). The 12-week
      PFS rates (61% vs 60%), median PFS (16.1 vs 13.1 weeks) and OS (9.2 vs 9.0
      months) times for patients who received, respectively, antihistamines with and
      without corticosteroids were similar. Cox regression modeling did not identify
      any impact of type of premedication used (antihistamine with or without
      corticosteroids) on the efficacy of treatment in relation to PFS or OS.
      CONCLUSIONS: : Prophylactically premedicating mCRC patients with both
      antihistamine and a corticosteroid appeared to reduce the frequency of cetuximab
      associated IRRs. Given that this was a post hoc analysis, caution must be
      exercised in the interpretation of these data, which require formal confirmation
      in a randomized study. Cancer 2010. (c) 2010 American Cancer Society.

PMID- 20143445
TI  - Killing tumor cells through their surface beta(2)-microglobulin or major
      histocompatibility complex class I molecules.
AB  - Targeted antibody-based therapy has been used successfully to treat cancers.
      Recent studies have demonstrated that tumor cells treated with antibodies
      specific for beta(2)-microglobulin (beta(2)M) or major histocompatibility complex
      (MHC) class I molecules undergo apoptosis in vitro and in vivo (mouse models).
      Antibodies against beta(2)M or MHC class I induce tumor cell apoptosis by 1)
      recruiting MHC class I molecules to lipid rafts and activating LYN kinase and the
      signal-transducing enzyme phospholipase C-gamma2-dependent c-Jun N-terminal
      kinase signaling pathway and 2) expelling interleukin 6 and insulin-like growth
      factor 1 receptors out of lipid rafts and inhibiting the growth and survival
      factor-induced activation of the phosphatidylinositol 3-kinase/Akt and
      extracellular signal-related kinase pathways. Consequently, mitochondrial
      integrity is compromised, and the caspase-9-dependent cascade is activated in
      treated tumor cells. However, although beta(2)M and MHC class I are expressed on
      normal hematopoietic cells, which is a potential safety concern, the monoclonal
      antibodies were selective to tumor cells and did not damage normal cells in vitro
      or in human-like mouse models. These findings suggest that targeting beta(2)M or
      MHC class I by using antibodies or other agents offers a potential therapeutic
      approach for beta(2)M/MHC class I-expressing malignancies. Cancer 2010. (c) 2010
      American Cancer Society.

PMID- 20143448
TI  - Evaluating the ability to detect change of health-related quality of life in
      children with Hodgkin disease.
AB  - BACKGROUND: We evaluated 4 different health-related quality of life (HRQL)
      measures prospectively to determine their ability to detect change over time: the
      Health Utilities Index Mark 2 and Mark 3, the Pediatric Quality of Life Inventory
      (PedsQL) 4.0 Generic Core and Cancer Module, the EuroQol EQ-5D visual analogue
      scale (EuroQol), and the Lansky Play-Performance Scale. METHODS: Children with
      all stages of Hodgkin disease from 12 centers across Canada were asked to
      complete the 4 measures at 4 time points: 2 weeks after the first course of
      chemotherapy, on the third day of the second course of chemotherapy, during the
      third week of radiation, and 1 year after diagnosis. RESULTS: Fifty-one patients
      were enrolled in the study between May 1, 2002 and March 31, 2005. Two patients
      were excluded: 1 patient died shortly after the first time point and the other
      patient failed to complete any of the questionnaires. All measures showed a
      significant change between Time 1 and Time 4 (<0.05). When the change in child
      scores was analyzed between the time points using the child's self-reported
      change in HRQL, the PedsQL and the EuroQol showed significant change at all time
      points. CONCLUSIONS: All of the measures were able to detect change in a diverse
      group of children with Hodgkin disease. The PedsQL and the EuroQol appeared to be
      the most sensitive to change.

PMID- 20143447
TI  - Ability of integrated positron emission and computed tomography to detect
      significant colonic pathology: the experience of a tertiary cancer center.
AB  - BACKGROUND: The ability of integrated positron emission tomography and computed
      axial tomography (PET-CT) to detect colonic pathology is not fully defined. The
      purpose of this study was to assess the ability of PET-CT to detect colonic
      pathology and to determine the significance of ((18)F)2-fluoro-2-deoxyglucose
      ((18)F-FDG) activity noted incidentally in the colon on PET-CT. METHODS: Records
      for all patients who underwent PET-CT and colonoscopy at our institution were
      reviewed. Patients with history of colonic malignancy or colon surgery were
      excluded. RESULTS: Fifty-eight patients had incidental colonic (18)F-FDG activity
      on PET (Group A) and 272 had none (Group B). In Group A, 65% of patients had
      pathologic findings detected on colonoscopy that corresponded to the site of PET
      activity. Standardized uptake value (SUV) readings were not helpful in
      distinguishing true-positives from false-positives. In Group B, 11.8% of patients
      were found to have significant colonic findings. Lesions not detected by PET-CT
      included 4 colon cancers, 7 advanced adenomas, and 10 patients with colonic
      lymphoma. Overall, the sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV), and accuracy of PET-CT for detecting significant
      pathology were 53%, 93%, 65%, 89%, and 85%, respectively. For detecting colon
      cancer and adenomas 10 mm or more, the sensitivity, specificity, PPV, NPV, and
      accuracy of PET-CT were 72%, 90%, 45%, 96%, and 88%, respectively. CONCLUSIONS:
      Incidental colonic activity detected by PET-CT warrants further evaluation with
      colonoscopy. However, negative PET-CT does not rule out significant colonic
      pathology including colon cancer, advanced adenomas, or lymphoma.

PMID- 20143449
TI  - Which AML subsets benefit from leukemic cell priming during chemotherapy? Long
      term analysis of the ALFA-9802 GM-CSF study.
AB  - BACKGROUND: : Priming with granulocytic hematopoietic growth factors may modulate
      cell cycle kinetics of leukemic cells and render them more susceptible to phase
      specific chemotherapeutic agents. In a first report, we have shown that priming
      with granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance
      complete remission (CR) rate and event-free survival (EFS) in younger adults with
      acute myeloid leukemia (AML). METHODS: : In this randomized trial, 259 patients
      with AML were randomized at baseline to receive or not receive GM-CSF
      concurrently with all cycles of chemotherapy. The effects of GM-CSF on survival
      were reported herein with a long-term follow-up and studied according to distinct
      biological subgroups defined on cytogenetics and molecular markers. RESULTS: :
      The EFS rate was better in the GM-CSF group (43% vs 34%; P = .04). GM-CSF did not
      improve the outcome in patients from good risk subgroups, while patients from
      poor risk subgroups benefited from GM-CSF therapy. In this population, the
      difference in terms of EFS probability was mainly observed in patients with high
      initial white blood cell count and in those with FLT3-ITD or MLL rearrangement.
      When combining these 2 molecular abnormalities for comparison of the effect of GM
      CSF priming, the difference in terms of EFS was highly significant (5-year EFS,
      39% with GM-CSF vs 8% without GM-CSF; P = .007). CONCLUSIONS: : Sensitization of
      leukemic cells and their progenitors by GM-CSF appears as a plausible strategy
      for improving the outcome of patients with newly diagnosed AML. Patients with
      poor-prognosis FLT3-ITD or MLL rearrangement might be a good target population to
      further investigate priming strategies. Cancer 2010. (c) 2010 American Cancer
      Society.

PMID- 20143450
TI  - Effects of zinc and cadmium on erythrocyte antioxidant systems of a freshwater
      fish Oreochromis niloticus.
AB  - In this work to determine the effects of metals exposure of Oreochromis niloticus
      on erythrocyte antioxidant systems, fish were exposed to 5.0 mg/L Zn, 1.0 mg/L
      Cd, and 5.0 mg/L Zn + 1.0 mg/L Cd mixtures for 7 and 14 days and reduced
      glutathione (GSH) level, catalase (CAT), and glucose-6-phosphate dehydrogenase
      (G6PD) activities were investigated. In addition, Zn or Cd levels in whole blood
      were studied. Erythrocyte GSH level and CAT and G6PD enzyme activities increased
      in response to single and combined Zn and Cd exposure. The elevation observed in
      the CAT activity was higher in the Cd alone, and in combination with Zn, than in
      Zn alone. Time-dependent alteration was not observed in all antioxidant
      parameters. Exposure to metals (alone and in mixture) resulted in elevatation of
      Zn and Cd levels in the blood. Concentration of metals in the blood of fish
      exposed to the Zn + Cd combination was lower than in fish exposed to the single
      metal. This study demonstrates that metals caused oxidative stress in fish
      erythrocytes, and an adaptation with an increase in CAT and G6PD activities and
      GSH level, which were important in the protection against metal damage, was
      observed.

PMID- 20143451
TI  - Inhibition by Cu2+ and Cd2+ of a mu-class glutathione S-transferase from shrimp
      Litopenaeus vannamei.
AB  - Glutathione S-transferases (GSTs) are a family of detoxifying enzymes that
      catalyze the conjugation of glutathione (GSH) to electrophiles, thereby
      increasing the solubility of xenobiotics and aiding its excretion from the cell.
      The present work presents the inhibition of a mu-class GST of the marine shrimp
      Litopenaeus vannamei by copper (Cu2+) and cadmium (Cd2+). The protein was
      overexpressed in bacteria and its enzymatic activity measured using 1-chloro-2,4
      dinitrobenzene. The mean inhibitory concentration (IC(50)) for shrimp GST against
      Cu2+) was 4.77 microM and for Cd2+ was 0.39 microM. A molecular model of the
      protein based on the crystal structure of a maize GST bound to cadmium showed
      that the metal binds in the GSH-binding site by coordination with Asp and Gln
      residues. These results are consistent with the experimental data and suggest
      that sublethal concentration of metals may affect the capacity of the organism to
      detoxify pesticides or xenobiotics.

PMID- 20143452
TI  - Small noncoding RNAs: biogenesis, function, and emerging significance in
      toxicology.
AB  - In recent years, the discovery of small ncRNAs (noncoding RNAs) has unveiled a
      slew of powerful riboregulators of gene expression. So far, many different types
      of small ncRNAs have been described. Of these, miRNAs (microRNAs), siRNAs (small
      interfering RNAs), and piRNAs (Piwi-interacting RNAs) have been studied in more
      detail. A significant fraction of genes in most organisms and tissues is targets
      of these small ncRNAs. Because these tiny RNAs are turning out to be important
      regulators of gene and genome expression, their aberrant expression profiles are
      expected to be associated with cellular dysfunction and disease. In fact, an ever
      increasing number of studies have implicated miRNAs and siRNAs in human health
      and disease ranging from metabolic disorders to diseases of various organ systems
      as well as various forms of cancer. Nevertheless, despite the flurry of research
      on these small ncRNAs, many aspects of their biology still remain to be
      understood. The following discussion focuses on some aspects of the biogenesis
      and function of small ncRNAs with major emphasis on miRNAs since these are the
      most widespread endogenous small ncRNAs that have been called "micromanagers" of
      gene expression. Their emerging significance in toxicology is also discussed.

PMID- 20143453
TI  - Splice variant specific increase in Ca2+/calmodulin-dependent protein kinase 1
      gamma mRNA expression in response to acute pyrethroid exposure.
AB  - In mammals, pyrethroids are neurotoxicants that interfere with ion channel
      function in excitable neuronal membranes. Previous work demonstrated increases in
      the expression of Ca(2+)/calmodulin-dependent protein kinase 1-gamma (Camk1g)
      mRNA following acute deltamethrin and permethrin exposure. In the rat, this gene
      is expressed as two distinct splice variants, Camk1g1 and Camk1g2. The present
      study tests the hypothesis that changes in Camk1g mRNA expression in the rat
      following acute pyrethroid exposure are due to a specific increase in the Camk1g1
      splice variant and not the Camk1g2 splice variant. Long-Evans rats were acutely
      exposed to permethrin, deltamethrin, or corn oil vehicle. Frontal cortex was
      collected at 6 h postdosing. In addition, rats were exposed to permethrin (100
      mg/kg) or deltamethrin (3 mg/kg), and frontal cortex was collected at 1, 3, 6, 9,
      12, or 24 h along with time-matched vehicle controls. Expression of Camk1g1 and
      Camk1g2 mRNA was measured by quantitative real-time RT-PCR and quantified using
      the 2(-Delta Delta C)T method. Dose-dependent increases in Camk1g1 mRNA
      expression were observed for both pyrethroids at 6 h. In addition, a dose
      dependent increase in Camk1g2 was observed at 6 h although it was very small in
      magnitude. The increases in Camk1g1 expression for deltamethrin and permethrin
      peak between 3 and 6 h postexposure and returns to control levels by 9 h. There
      was no increase in CAMK1G1 protein as measured with Western blots. The present
      data demonstrate that pyrethroid-induced changes in Camk1g are driven mainly by
      increased expression of the Camk1g1 splice variant.

PMID- 20143454
TI  - Sulfur mustard induced cytokine production and cell death: investigating the
      potential roles of the p38, p53, and NF-kappaB signaling pathways with RNA
      interference.
AB  - Cutaneous and ocular injuries caused by sulfur mustard (SM; bis-(2-chloroethyl)
      sulfide) are characterized by severe inflammation and death of exposed cells.
      Given the known roles of p38MAPK and NF-kappaB in inflammatory cytokine
      production, and the known roles of NF-kappaB and p53 in cell fate, these pathways
      are of particular interest in the study of SM injury. In this study, we utilized
      inhibitory RNA (RNAi) targeted against p38 alpha, the p50 subunit of NF-kappaB,
      or p53 to characterize their role in SM-induced inflammation and cell death in
      normal human epidermal keratinocytes (NHEK). Analysis of culture supernatant from
      200 microM SM-exposed cells showed that inflammatory cytokine production was
      inhibited by p38 alpha RNAi but not by NF-kappaB p50 RNAi. These findings further
      support a critical role for p38 in SM-induced inflammatory cytokine production in
      NHEK and suggest that NF-kappaB may not play a role in the SM-induced
      inflammatory response of this cell type. Inhibition of NF-kappaB by p50 RNAi did,
      however, partially inhibit SM-induced cell death, suggesting a role for NF-kappaB
      in SM-induced apoptosis or necrosis. Interestingly, inhibition of p53 by RNAi
      potentiated SM-induced cell death, suggesting that the role of p53 in SM injury,
      may be complex and not simply prodeath.

PMID- 20143455
TI  - Evaluation of comparative effect of pre- and posttreatment of selenium on mercury
      induced oxidative stress, histological alterations, and metallothionein mRNA
      expression in rats.
AB  - To evaluate the effect of pre- or posttreatment of selenium (6 micromol/kg b.w.,
      single intraperitoneal injection) in mercury intoxication, rats were exposed to
      mercury (12 micromol/kg b.w., single intraperitoneal injection). Exposure to
      mercury resulted in induced oxidative stress in liver, kidney, and brain tissues.
      Marked changes in serum biochemical parameters together with alterations in
      histopathology and an induction in metallothionein-I and metallothionein-II mRNA
      expression in the liver and kidney were observed. Pretreatment with selenium to
      mercury-exposed animals had protective effect on the liver, whereas posttreatment
      had partial protection on restoration of altered oxidative stress parameters. In
      the kidney, pretreatment with selenium showed partial protection on restoration
      of altered biochemical parameters, whereas no protection was observed in
      posttreatment. The pretreatment with selenium resulted in restoration of mercury
      induced metallothionein-I and metallothionein-II mRNA expression, which was
      completely restored in the liver whereas partial restoration was observed in the
      kidney. Posttreatment with selenium resulted in further induction in
      metallothionein-I and metallothionein-II mRNA expression in the liver and kidney.
      In the brain, selenium showed partial protection on alerted biochemical
      parameters. Results indicate that pretreatment with selenium is beneficial in
      comparison to posttreatment in mercury intoxication. Thus, dietary intake of
      selenium within safe limit may, therefore, enable us in combating any foreseen
      effects due to mercury exposure.

PMID- 20143456
TI  - Smoking initiation in Germany: the role of intergenerational transmission.
AB  - This paper analyzes the decision to start smoking using data from the German
      Socio-Economic Panel (GSOEP). Our focus is on the role that parental smoking
      behavior plays for children's smoking initiation. The data used are a combination
      of retrospective information on the age individuals started smoking and, by
      tracing back these individuals within the panel structure up to that point,
      information on characteristics at the age of smoking initiation. In contrast to
      the previous literature it is possible to control for the environment at the time
      of smoking onset that might have influenced the decision to start. Our preferred
      specification of a discrete time hazard model indicates that parental smoking
      significantly increases the offspring's hazard to start smoking. While this
      effect is most prominent for currently smoking parents, it is also found for
      parents who have given up smoking already. However, an ambiguous effect of the
      timing of parental smoking cessation is found, arguing against role-model effects
      being a key determinant for smoking initiation.

PMID- 20143458
TI  - Is the control of dietary cholesterol intake sufficiently effective to ameliorate
      nonalcoholic fatty liver disease?
AB  - In our examination of the distribution of abdominal fat, dietary intake and
      biochemical data in patients with nonalcoholic fatty liver disease (NAFLD), non
      obese NAFLD patients without insulin resistance presented a characteristic
      pattern of dietary intake. Dietary cholesterol intake was superabundant in non
      obese patients compared with obese patients, although total energy and
      carbohydrate intake was not excessive. Namely, excess cholesterol intake appears
      to be one of the main factors associated with NAFLD development and liver injury.
      Therefore, the control of dietary cholesterol intake may lead to an improvement
      in NAFLD, and the NPC1L1 inhibitor ezetimibe might be a promising treatment for
      NAFLD. We review one pathogenic aspect of lipid metabolism dysregulation in NAFLD
      and survey new strategies for NAFLD treatment based on the modification of
      cholesterol metabolism.

PMID- 20143457
TI  - Ontogeny, growth and development of the small intestine: Understanding pediatric
      gastroenterology.
AB  - Throughout our lifetime, the intestine changes. Some alterations in its form and
      function may be genetically determined, and some are the result of adaptation to
      diet, temperature, or stress. The critical period programming of the intestine
      can be modified, such as from subtle differences in the types and ratios of n3:m6
      fatty acids in the diet of the pregnant mother, or in the diet of the weanlings.
      This early forced adaptation may persist in later life, such as the unwanted
      increased intestinal absorption of sugars, fatty acids and cholesterol. Thus, the
      ontogeny, early growth and development of the intestine is important for the
      adult gastroenterologist to appreciate, because of the potential for these early
      life events to affect the responsiveness of the intestine to physiological or
      pathological challenges in later life.

PMID- 20143459
TI  - Current indications and role of surgery in the management of sigmoid
      diverticulitis.
AB  - Sigmoid diverticulitis is a common disease which carries both a significant
      morbidity and a societal economic burden. This review article analyzes the
      current data regarding management of sigmoid diverticulitis in its variable
      clinical presentations. Wide-spectrum antibiotics are the standard of care for
      uncomplicated diverticulitis. Recently published data indicate that sigmoid
      diverticulitis does not mandate surgical management after the second episode of
      uncomplicated disease as previously recommended. Rather, a more individualized
      approach, taking into account frequency, severity of the attacks and their impact
      on quality of life, should guide the indication for surgery. On the other hand,
      complicated diverticular disease still requires surgical treatment in patients
      with acceptable comorbidity risk and remains a life-threatening condition in the
      case of free peritoneal perforation. Laparoscopic surgery is increasingly
      accepted as the surgical approach of choice for most presentations of the disease
      and has also been proposed in the treatment of generalized peritonitis. There is
      not sufficient evidence supporting any changes in the approach to management in
      younger patients. Conversely, the available evidence suggests that surgery should
      be indicated after one attack of uncomplicated disease in immunocompromised
      individuals. Uncommon clinical presentations of sigmoid diverticulitis and their
      possible association with inflammatory bowel disease are also discussed.

PMID- 20143461
TI  - Diffusion-weighted MRI in abdominal oncology: clinical applications.
AB  - Diffusion-weighted magnetic resonance imaging (DWI) provides image contrast that
      is different from that obtained by conventional magnetic resonance techniques.
      Although previously, DWI has been used to evaluate various diseases of the
      central nervous system, several technical advances have expanded the clinical
      applications of DWI beyond the central nervous system. As a result, many reports
      have been published on the use of DWI in abdominal diseases. Particularly,
      abdominal DWI has now being focused on evaluation of patients with abdominal
      cancer. DWI can be used for pretreatment tumor detection, characterization
      including predicting tumor response to therapy, monitoring tumor response during
      therapy, and follow-up study after treatment to detect possible tumor recurrence.

PMID- 20143462
TI  - Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral
      pain in rats.
AB  - AIM: To investigate the pharmacological effect of JCM-16021, a Chinese herbal
      formula, and its underlying mechanisms. METHODS: JCM-16021 is composed of seven
      herbal plant materials. All raw materials of the formula were examined according
      to the quality control criteria listed in the Chinese Pharmacopeia (2005). In a
      neonatal maternal separation (NMS) model, male Sprague-Dawley rats were submitted
      to daily maternal separation from postnatal day 2 to day 14, or no specific
      handling (NH). Starting from postnatal day 60, rats were administered JCM-16021
      (2, 4, 8 g/kg per day) orally twice a day for 28 d. Pain threshold pressure and
      electromyographic activities of external oblique muscles in response to
      colorectal distention recorded with a Power Lab System (AD Instruments
      International), were tested as pain indices. Changes in serotonin (5-HT) and 5
      hydroxyindoleacetic acid (5-HIAA) concentrations in the colon of rats were
      analyzed; the enterochromaffin cell numbers and serotonin transporter in the
      colon of rats were also evaluated with an immunohistochemistry method. RESULTS:
      NMS treatment significantly reduced pain threshold pressure (37.4 +/- 1.4 mmHg),
      as compared to that of NH rats (57.7 +/- 1.9 mmHg, P < 0.05). After JCM-16021
      treatment, the pain threshold pressure significantly increased when compared to
      that before treatment (34.2 +/- 0.9 mmHg vs 52.8 +/- 2.3 mmHg in the high dose
      group, 40.2 +/- 1.6 mmHg vs 46.5 +/- 1.3 mmHg in the middle dose group, and 39.3
      +/- 0.7 mmHg vs 46.5 +/- 1.6 mmHg in the low dose group, P < 0.05). Also JCM
      16021 significantly and dose-dependently decreased electromyographic activity to
      the graded colorectal distension (CRD), (the mean DeltaAUC values were: 0.17 +/-
      0.03, 0.53 +/- 0.15, 1.06 +/- 0.18, 1.22 +/- 0.24 in the high dose group; 0.23 +/
      0.04, 0.68 +/- 0.17, 1.27 +/- 0.26, 1.8 +/- 0.3 in the middle dose group; and
      0.29 +/- 0.06, 0.8 +/- 0.16, 1.53 +/- 0.24, 2.1 +/- 0.21 in the low dose group
      for the pressures 20, 40, 60, 80 mmHg), as compared to the NMS vehicle group. The
      mean DeltaAUC values were: 0.57 +/- 0.12, 1.33 +/- 0.18, 2.57 +/- 0.37, 3.08 +/-
      0.37 for the pressures 20, 40, 60, 80 mmHg (P < 0.05). JCM-16021 treatment
      significantly reduced the 5-HT concentrations (from high, middle and low dosage
      groups: 60.25 +/- 5.98 ng/100 mg, 60.32 +/- 4.22 ng/100 mg, 73.31 +/- 7.65 ng/100
      mg), as compared to the NMS vehicle groups (93.11 +/- 9.85 ng/100 mg, P < 0.05);
      and increased the 5-HIAA concentrations (after treatment, from high, middle and
      low dosage groups: 54.24 +/- 3.27 ng/100 mg, 50.34 +/- 1.26 ng/100 mg, 51.37 +/-
      2.13 ng/100 mg) when compared to that in the NMS vehicle group (51.75 +/- 1.98
      ng/100 mg, P < 0.05); but did not change the enterochromaffin cell numbers in the
      colon of rats. In addition, NMS rats had higher SERT expression (n = 10) than NH
      rats (n = 8, P < 0.05). JCM-16021 treatment significantly decreased SERT
      expression when compared to the NMS group (P < 0.01-0.001). CONCLUSION: JCM-16021
      can attenuate visceral hypersensitivity, and this analgesic effect may be
      mediated through the serotonin signaling pathway in the colon of rats.

PMID- 20143463
TI  - Celecoxib inhibits Helicobacter pylori colonization-related factors.
AB  - AIM: To investigate the effect of celecoxib, a selective COX-2 inhibitor, on
      Helicobacter pylori (H. pylori) colonization-related factors and its mechanism.
      METHODS: After co-incubation with celecoxib, morphology of H. pylori strain 26695
      was observed under a transmission electron microscope. Flagella motility was
      assessed by stab agar motility test. Adherence of H. pylori to AGS cells was
      determined by enzyme linked immunosorbent assay. Levels of mRNA expression in
      flagellar genes (flaA, flaB), urease genes (ureA, ureB) and adhesin genes (babA,
      sabA, alpA, alpB, hpaA, hopZ) were measured by real-time polymerase chain
      reaction. RESULTS: Separation and non-integrity of bacterial cell wall,
      rarefaction and asymmetry of cytoplasm, and even lysis of H. pylori were observed
      in the presence of celecoxib. When H. pylori strains were incubated in the
      presence of celecoxib, their flagellar motility and adherence to AGS cells were
      inhibited. The expression of ureA, ureB, babA, sabA, alpA, alpB, hpaA, hopZ was
      up-regulated while the expression of flaA, flaB was down-regulated in the
      presence of celecoxib. CONCLUSION: Celecoxib inhibits flagellar motility and
      adherence of H. pylori to AGS cells, and destructs their normal structure in
      vitro.

PMID- 20143460
TI  - Vascular invasion in pancreatic cancer: Imaging modalities, preoperative
      diagnosis and surgical management.
AB  - Pancreatic cancer is associated with a poor prognosis, and surgical resection
      remains the only chance for curative therapy. In the absence of metastatic
      disease, which would preclude resection, assessment of vascular invasion is an
      important parameter for determining resectability of pancreatic cancer. A
      frequent error is to misdiagnose an involved major vessel. Obviously, surgical
      exploration with pathological examination remains the "gold standard" in terms of
      evaluation of resectability, especially from the point of view of vascular
      involvement. However, current imaging modalities have improved and allow
      detection of vascular invasion with more accuracy. A venous resection in
      pancreatic cancer is a feasible technique and relatively reliable. Nevertheless,
      a survival benefit is not achieved by curative resection in patients with
      pancreatic cancer and vascular invasion. Although the discovery of an arterial
      invasion during the operation might require an aggressive management, discovery
      before the operation should be considered as a contraindication. Detection of
      vascular invasion remains one of the most important challenges in pancreatic
      surgery. The aim of this article is to provide a complete review of the different
      imaging modalities in the detection of vascular invasion in pancreatic cancer.

PMID- 20143464
TI  - MicroRNA155 is induced in activated CD4(+) T cells of TNBS-induced colitis in
      mice.
AB  - AIM: To investigate the expression of microRNA155 (miRNA155) in trinitrobenzene
      sulphonic acid (TNBS)-induced colitis and the relationship between miRNA155 and
      tumor necrosis factor (TNF) expressions. METHODS: In TNBS colitis mice, miRNA155
      and TNF mRNA expressions were measured in colons and CD4(+) T cells of draining
      lymph nodes (LNs). CD4(+) T cells were cultured in vitro with or without anti
      CD3/CD28 antibody, and the expressions of miRNA155 and TNF mRNA in cells and TNF
      concentration in culture media were examined. RESULTS: miRNA155 and TNF mRNA
      expressions in colons and in cells of LNs were significantly increased in TNBS
      colitis compared with controls. In TNBS colitis, miRNA155 and TNF mRNA
      expressions in CD4(+) T cells of LNs and TNF concentration in CD4(+) T cells
      culture media increased compared with controls. When cultured with anti-CD3/CD28
      antibody, miRNA155 and TNF mRNA expressions in CD4(+) T cells and TNF
      concentration in the CD4(+) T cells culture media were significantly higher than
      those cultured without anti-CD3/CD28 antibody. Following analysis using the
      Pearson's correlation coefficient, miRNA155 expression had a significant positive
      correlation with either TNF mRNA expression in CD4(+) T cells (r = 0.860, P <
      0.05) or TNF concentration in CD4(+) T cells culture media (r = 0.892, P < 0.05).
      CONCLUSION: miRNA155 is induced in colons and activated CD4(+) T cells in TNBS
      colitis, and the levels of miRNA155 and TNF expressions have a significant
      positive correlation.

PMID- 20143466
TI  - Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally
      advanced gastric cancer.
AB  - AIM: To investigate feasibility, morbidity and surgical mortality of a docetaxel
      based chemotherapy regimen randomly administered before or after gastrectomy in
      patients suffering from locally-advanced resectable gastric cancer. METHODS:
      Patients suffering from locally-advanced (T3-4 any N M0 or any T N1-3 M0) gastric
      carcinoma, staged with endoscopic ultrasound, bone scan, computed tomography, and
      laparoscopy, were assigned to receive four 21 d/cycles of TCF (docetaxel 75
      mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2) per day
      for days 1-14), either before (Arm A) or after (Arm B) gastrectomy. Operative
      morbidity, overall mortality, and severe adverse events were compared by
      intention-to-treat analysis. RESULTS: From November 1999 to November 2005, 70
      patients were treated. After preoperative TCF (Arm A), thirty-two (94%)
      resections were performed, 85% of which were R0. Pathological response was
      complete in 4 patients (11.7%), and partial in 18 (55%). No surgical mortality
      and 28.5% morbidity rate were observed, similar to those of immediate surgery arm
      (P = 0.86). Serious chemotherapy adverse events tended to be more frequent in arm
      B (23% vs 11%, P = 0.07), with a single death per arm. CONCLUSION: Surgery
      following docetaxel-based chemotherapy was safe and with similar morbidity to
      immediate surgery in patients with locally-advanced resectable gastric carcinoma.

PMID- 20143467
TI  - A novel cleansing score system for capsule endoscopy.
AB  - AIM: To suggest a new cleansing score system for small bowel preparation and to
      evaluate its clinical efficacy. METHODS: Twenty capsule endoscopy cases were
      reviewed and small bowel preparation was assessed with the new scoring system.
      For the assessment, two visual parameters were used: proportion of visualized
      mucosa and degree of obscuration. Representative frames from small bowel images
      were serially selected and scored at 5-min intervals. Intraclass correlation
      coefficient (ICC) was obtained to assess the reliability of the new scoring
      system. For efficacy evaluation and validation, scores of our new scoring system
      were compared with another previously reported cleansing grading system. RESULTS:
      Concordance with the previous system, inter-observer agreement, and intra-patient
      agreement were excellent with ICC values of 0.82, 0.80, and 0.76, respectively.
      The intra-observer agreements at four-week intervals were also excellent. The cut
      off value of adequate image quality was found to be 2.25. CONCLUSION: Our new
      scoring system is simple, efficient, and can be considered to be applicable in
      clinical practice and research.

PMID- 20143465
TI  - Colorectal cancer prognosis twenty years later.
AB  - AIM: To evaluate changes in colorectal cancer (CRC) survival over the last 20
      years. METHODS: We compared two groups of consecutive CRC patients that were
      prospectively recruited: Group I included 1990 patients diagnosed between 1980
      and 1994. Group II included 871 patients diagnosed in 2001. RESULTS: The average
      follow up time was 21 mo (1-229) for Group I and 50 mo (1-73.4) for Group II.
      Overall median survival was significantly longer in Group II than in Group I (73
      mo vs 25 mo, P < 0.001) and the difference was significant for all tumor stages.
      Post surgical mortality was 8% for Group Iand 2% for Group II (P < 0.001). Only
      17% of GroupI patients received chemotherapy compared with 50% of Group II
      patients (P < 0.001). CONCLUSION: Survival in colorectal cancer patients has
      doubled over the past 20 years. This increase seems to be partly due to the
      generalization in the administration of chemotherapy and to the decrease of post
      surgical mortality.

PMID- 20143468
TI  - Etiological and clinicopathologic characteristics of intrahepatic
      cholangiocarcinoma in young patients.
AB  - AIM: To investigate the prevalence, risk factors, and clinicopathologic
      characteristics of intrahepatic cholangiocarcinoma (ICC) in young patients.
      METHODS: A retrospective analysis was performed in ICC patients referred to the
      Eastern Hepatobiliary Surgery Hospital in Shanghai, China. Among 317
      consecutively enrolled patients, 40 patients were aged <or= 40 years (12.61%). We
      compared the risk factors and clinicopathologic characteristics of these patients
      (group I: n = 40) with those aged > 40 years (group II: n = 277). RESULTS: Group
      I had distinct features compared with group II, including a low frequency of
      hepatolithiasis (P = 0.000); a high positive rate of serum hepatitis B surface
      antigen (P = 0.000) and hepatitis B virus (HBV)-associated cirrhosis (P = 0.038);
      a high frequency of alpha-fetoprotein (> 400 microg/L) (P = 0.011); a low
      frequency of carbohydrate antigen 19-9 (> 37 U/mL) (P = 0.017); and a high
      frequency of liver histological inflammation (P = 0.002). Although there was no
      significant difference between the two groups in regards to hepatic
      schistosomiasis, alcohol-associated cirrhosis and cirrhosis due to other causes
      (P > 0.05), they only occurred in the elderly group. CONCLUSION: The risk factors
      are significantly different between young and elderly ICC patients. HBV and HBV
      associated cirrhosis are the most important risk factors for young ICC patients.

PMID- 20143469
TI  - Does Helicobacter pylori infection play a role in iron deficiency anemia? A meta
      analysis.
AB  - AIM: To perform a meta-analysis of observational studies and randomized
      controlled trials (RCTs) on the association between Helicobacter pylori (H.
      pylori) and iron deficiency anemia (IDA). METHODS: A defined search strategy was
      used to search Medline, Embase, the Cochrane Library, Clinical Trials, Cochrane
      Central Register of Controlled Trials, Premedline and Healthstar. Odds ratio (OR)
      was used to evaluate observational epidemiology studies, and weighted mean
      difference (WMD) was used to demonstrate the difference between control and
      intervention groups. RESULTS: Fifteen observational studies and 5 RCTs were
      identified and used for calculation. The pooled OR for observational studies was
      2.22 (95% CI: 1.52-3.24, P < 0.0001). The WMD for hemoglobin (HB) was 4.06 g/L
      (95% CI: -2.57-10.69, P = 0.01), and the WMD for serum ferritin (SF) was 9.47
      mug/L (95% CI: -0.50-19.43, P < 0.0001). Results were heterogeneous for all
      comparisons. CONCLUSION: This meta-analysis on observational studies suggests an
      association between H. pylori and IDA. In RCTs, eradication of H. pylori can
      improve HB and SF levels but not significantly.

PMID- 20143470
TI  - Betaine inhibits toll-like receptor 4 expression in rats with ethanol-induced
      liver injury.
AB  - AIM: To test whether ethanol feeding could induce Toll-like receptor 4 (TLR4)
      responses, assess the hepatoprotective effect of betaine and its inhibitive
      effect on TLR4 in animal models of alcoholic liver injury. METHODS: Forty-eight
      female Sprague-Dawley rats were randomly divided into four groups as control,
      model, low and high dose betaine groups. Except control group, all rats were fed
      with high fat-containing diet plus ethanol and fish oil gavages for 8 wk. Betaine
      was administered intragastrically after exposure of ethanol for 4 wk. The changes
      of liver histology were examined. The expression of TLR4 mRNA and protein was
      detected by RT-PCR and Western blot, respectively. The serum aminotransferase
      activity [alanine transarninase (ALT), aspartate aminotransferase (AST)], serum
      endotoxin, and liver inflammatory factors [tumor necrosis factor-alpha (TNF
      alpha), interferon-gamma (IFN-gamma), interleukin-18 (IL-18)] were also assayed.
      RESULTS: Compared with control group, rats of model group developed marked liver
      injury, accompanied by an increase of ALT (159.41 +/- 7.74 U/L vs 59.47 +/- 2.34
      U/L, P < 0.0001), AST (248.25 +/- 1.40 U/L vs 116.89 +/- 3.48 U/L, P < 0.0001),
      endotoxin (135.37 +/- 30.17 ng/L vs 44.15 +/- 7.54 ng/L, P < 0.0001), TNF-alpha
      (20.81 +/- 8.58 pg/mL vs 9.34 +/- 2.57 pg/mL, P = 0.0003), IFN-gamma (30.18 +/-
      7.60 pg/mL vs 16.86 +/- 9.49 pg/mL, P = 0.0039) and IL-18 (40.99 +/- 8.25 pg/mL
      vs 19.73 +/- 9.31 pg/mL, P = 0.0001). At the same time, the expression of TLR4
      mRNA and protein was markedly induced in the liver after chronic ethanol
      consumption (1.45 +/- 0.07 vs 0.44 +/- 0.04, P < 0.0001; 1.83 +/- 0.13 vs 0.56 +/
      0.08, P < 0.0001). Compared with model group, betaine feeding resulted in
      significant decreases of ALT (64.93 +/- 6.06 U/L vs 159.41 +/- 7.74 U/L, P <
      0.0001), AST (188.73 +/- 1.11 U/L vs 248.25 +/- 1.40 U/L, P < 0.0001), endotoxin
      (61.80 +/- 12.56 ng/L vs 135.37 +/- 30.17 ng/L, P < 0.0001), TNF-alpha (9.79 +/-
      1.32 pg/mL vs 20.81 +/- 8.58 pg/mL, P = 0.0003), IFN-gamma (18.02 +/- 5.96 pg/mL
      vs 30.18 +/- 7.60 pg/mL, P = 0.0008) and IL-18 (18.23 +/- 7.01 pg/mL vs 40.99 +/-
      8.25 pg/mL, P < 0.0001). Betaine also improved liver steatosis. The expression
      levels of TLR4 mRNA or protein in liver tissues were significantly lowered (0.62
      +/- 0.04 vs 1.45 +/- 0.07, P < 0.0001; and 0.65 +/- 0.06 vs 1.83 +/- 0.13, P <
      0.0001). There was a statistical difference of TLR4 mRNA and protein expression
      between high- and low-dose betaine groups (0.62 +/- 0.04 vs 0.73 +/- 0.05, P <
      0.0001, and 0.65 +/- 0.06 vs 0.81 +/- 0.09, P < 0.0001). CONCLUSION: Betaine can
      prevent the alcohol-induced liver injury effectively and improve the liver
      function. The expression of TLR4 increases significantly in ethanol-fed rats and
      betaine administration can inhibit TLR4 expression.

PMID- 20143471
TI  - Role of RECK methylation in gastric cancer and its clinical significance.
AB  - AIM: To investigate the relation between RECK methylation and clinicopathological
      characteristics of gastric cancer patients and evaluate the role of RECK
      methylation in peritoneal metastasis of gastric cancer. METHODS: Methylation of
      RECK gene in 40 paired samples of gastric cancer and its corresponding adjacent
      normal mucosa, lymph nodes and peritoneal irrigation fluid was detected by
      methylation-specific polymerase chain reaction. RESULTS: Aberrant methylation of
      RECK gene was detected in 27.5% (11/40) of the adjacent normal mucosa samples, in
      47.5% (19/40) of gastric cancer samples, in 57.1% (12/21) of the lymph node
      samples, and in 35% (14/40) of peritoneal irrigation fluid samples, respectively,
      with a significant difference between the adjacent normal mucosa and lymph node
      samples (P = 0.023). Presence of RECK methylation in the primary tumor samples
      was significantly correlated with tumor invasion (P = 0.023). The accuracy of
      RECK methylation in peritoneal lavage fluid samples for the diagnosis of
      peritoneal metastasis of gastric cancer was 72.5% (26/40), with a sensitivity of
      66.7% (6/9) and a specificity of 74.2% (23/31). CONCLUSION: Aberrant methylation
      of RECK gene may provide useful information for the early diagnosis and treatment
      of peritoneal metastasis of gastric cancer.

PMID- 20143472
TI  - Successful endoscopic procedures for intraductal papillary neoplasm of the bile
      duct: a case report.
AB  - Attention has recently been focused on biliary papillary tumors as the novel
      disease entity intraductal papillary neoplasm of the bile duct (IPNB), which
      consists of papillary proliferation of dysplastic biliary epithelium. As even
      benign papillary tumors are considered as premalignant, some investigators
      recommend aggressive surgical therapy for IPNB, although no guidelines are
      available to manage this disease. Few reports have described long-term follow-up
      of patients with benign IPNB without radical resection. If patients with IPNB who
      are treated only with endoscopic procedures are noted, clinical profiles and
      alternative therapies other than resection may be recommended. We report the case
      of a patient who experienced repetitive cholangitis for 10 years and was finally
      diagnosed with IPNB. Radical resection could not be recommended because of the
      age of the patient, therefore, endoscopic sphincterotomy was performed. Although
      an endoscopic retrograde biliary drainage catheter was placed several times for
      repetitive cholangitis, the patient has done well during follow-up. Our case may
      offer insights into the natural course and management decisions for the novel
      disease entity of IPNB.

PMID- 20143473
TI  - Monocyte chemotactic protein-1 gene polymorphism and spontaneous bacterial
      peritonitis.

PMID- 20143474
TI  - Abdominal pain in young children: two new studies: colic in infants . . . are we
      getting closer to understanding its cause?

PMID- 20143475
TI  - . . . And a simple way to manage functional abdominal pain in children?

PMID- 20143476
TI  - Probiotics for colds and flu in children.

PMID- 20143477
TI  - What to do with unused medications?

PMID- 20143479
TI  - [Questions for doctor Patrick Atienza].

PMID- 20143478
TI  - Youth engagement and suicide risk: testing a mediated model in a Canadian
      community sample.
AB  - Suicide is a leading cause of death among adolescents in many industrialized
      countries. We report evidence from a mediation model linking greater youth
      activity engagement, spanning behavioral and psychological components, with lower
      suicide risk through five hypothesized intrapersonal and interpersonal mediating
      factors. Self-report survey data (15% French, 85% English) were gathered from a
      community sample of 5,015 Canadian adolescents participating in a mental health
      promotion program. Youth (M(age) = 15.77, SD = 1.42, 50% female) were from two
      urban centers in southern Ontario, Canada. Youth engagement (youth's most
      important type of activity, frequency of involvement, and psychological
      engagement), suicide risk predictive factors (self-esteem, current concerns,
      depressive symptoms, coping ability, and connections with others), and suicide
      risk (ideation and attempts) were assessed. Consistent with the hypothesized
      mediation model, enjoyment and stress in youth's most important activity and
      various activity types were associated with the various hypothesized suicide risk
      predictive factors, which in turn were related to suicide risk. Implications for
      conceptualizations of youth engagement as a multidimensional construct and for
      suicide risk prevention efforts are discussed.

PMID- 20143480
TI  - Health risk assessment of essential metals. Proceedings of a workshop. May 2008.
      Ottawa, Ontario, Canada.

PMID- 20143481
TI  - Overall burden of GORD in human terms and in terms of costs is significant.
      Foreword.

PMID- 20143482
TI  - [The stages of formation and development of the state sanitary inspectorate of
      Moscow].
AB  - The state sanitary-and-epidemiological service of Russia is 86 years old. Since
      the Decree of RSFSR Council of People's Commissars "On Sanitary Organs of the
      Republic" was issued in 1922, which determined the basic principles of state
      sanitary inspection, the service has undergone its decisive stages of its
      development. In this connection, the history of birth, formation, and development
      of the Moscow sanitary-and-epidemiological service assumes paramount importance
      for its specialists.

PMID- 20143483
TI  - [Interaction of the bodies and institutions of the Russian Inspectorate for the
      protection of consumer rights and human welfare on sanitary-and-epidemiological
      examinations and issuing sanitary-and-epidemiological opinions].
AB  - The paper describes problems in the organization of the interaction of the
      Russian Inspectorate for the Protection of Consumer Rights and Human Welfare in
      Moscow and the Center for Hygiene and Epidemiology in Moscow to perform sanitary
      and-epidemiological examinations and to issue sanitary-and-epidemiological
      opinions. The goals of setting up a one-window service and measures required for
      its effective work are defined. Positive results of one-window activities are
      shown.

PMID- 20143484
TI  - [Supervision of the sanitary-helminthological state of soil in the inhabited
      areas of Moscow].
AB  - In accordance with the normative and methodical documents [3-5, 7-9], a complex
      of organizational, sanitary, and antiepidemic actions is performed to protect
      soil from causative agents of parasitic diseases in Moscow. About 2000 soil
      samples are annually taken from the playgrounds of children's educational
      establishments and apartment houses and tested. The soil contamination averages
      3.2%. It has been established that there are no sanitary-and-epidemiological
      opinions as to the parasitic safety of sand or lids on the sand-boxes on the
      playgrounds from which the soil or sand samples show causative agents of
      parasitic diseases (most commonly toxocariasis) and which are accessible to stray
      and domestic dogs. In 2005, DESINBAC super having bactericidal, fungicidal,
      sporocidal, and virocidal activities and ovicidal properties was approved for
      soil disinfection in the Russian Federation. The prevention of toxocariasis is a
      state problem. Executive bodies, housing-and-communal services, veterinary
      stations, and health care services with the participation of sanitary-and
      epidemiological facilities and their control must take part in solving this
      problem.

PMID- 20143485
TI  - [Hygienic requirements for transportation of industrial waste and consumption
      residues].
AB  - All wishing legal persons and individual entrepreneurs are presently engaged in
      garbage disposal Sanitary-and-epidemiological examination of activities in
      transportation of waste is complicated by that the existing sanitary regulations
      lack no requirements for storage, repair, washing, sanitization of waste-carrying
      transport, particularly epidemiologically dangerous (domestic, food, and
      biological waste, animal excreta, cut hair, etc.).

PMID- 20143486
TI  - [Prophylactic requirements for sanitary and epidemiological surveillance in
      dentistry].
AB  - The paper outlines the requirements for sanitary-and-epidemiological surveillance
      to prevent dental diseases. The investigations pose tasks to medical prevention
      centers to solve the problems in tooth prophylaxis, such as organizational-and
      methodological, sanitary-and-educational, health-improving, and others. The
      sanitary-and-hygienic requirements for therapeutic-and-prophylactic dental
      facilities are defined. A procedure for keeping a management protocol for the
      prevention of tooth diseases is described.

PMID- 20143487
TI  - [The hygienic requirements for the organization of prehouse areas to create good
      living conditions for the population].
AB  - The paper considers the organization of prehouse areas, their improvement, and
      the adequate space of these prehouse territories to create good living conditions
      for the population. It has been found that the assessment of the existing town
      planning situation in Moscow and the evaluation of the adopted functional zoning
      in the general town planning scheme for the city and administrative districts,
      and decision-making on the population's complaints require the estimation of the
      balance of a residential territory to develop normative requirements for this
      problem when considering the preconstruction proposals on location of variously
      purposeful projects in more detail, by analyzing the town-planning situation.

PMID- 20143488
TI  - [Population health risk assessment on designing the transport streams of Moscow].
AB  - The population health risk was assessed in the microdistricts adjacent to a
      future road interchange area in Moscow. Its possible negative impact was studied
      by many parameters, including the carcinogenic risk. Evidence is provided to a
      need for planning decisions on the optimization and reduction of the possible
      risk.

PMID- 20143489
TI  - [Future built-up area zoning by applying the methodology for assessing the
      population health risk].
AB  - Using the methodology for assessing the population health risk provides proposals
      on the functional zoning of the reorganized area of a plastics-works. An area has
      been allocated for possible house-building.

PMID- 20143490
TI  - [Occupational hygiene and hygienic regulations during the manufacture, use and
      utilization of nanomaterials].
AB  - This paper gives information on the action of nanoparticles when interacting with
      biological objects and penetrating into them. The high chemical activity of
      nanoparticles determines their enhanced biological activity against living
      organisms. Due to their special properties and sizes, the nanoparticles can
      penetrate across the cell membranes or between the cells and spread to various
      organs and systems by different mechanisms (endocytosis and transcytosis). In
      vitro and in vitro investigations of human exposure to nanopowders strongly
      suggest the occurrence of inflammatory processes, oxidative stresses in the lung
      and peripheral organs when such powders are inhaled. A few days after intracheal
      administration, the nanoparticles (30-60 nm in size) penetrate into the cells of
      the liver, kidney, and gonads and, moreover, primarily impair the mitochondria
      and penetrate into the nucleus, carrying the viruses on their arms into the cell
      nucleus. By taking into account the penetrating capacity of nanoparticles into
      various human organs and tissues and into cell substances, there are a number of
      problems and questions as both positive in the use of nanoparticles in medicine
      and other branches of industry as materials that can deliver a drug to the
      involved organs, by improving the properties of many materials, and negative,
      such as the development of new forms of abnormalities that are still unknown
      medicine. In this connection, it is necessary to develop technical regulations on
      their manufacture, use, storage, transportation, and utilization and those on the
      realization of various imported materials containing the nanoparticles and
      obtained by nanotechnologies.

PMID- 20143491
TI  - [Consumption of iodinated salt by the Moscow population to prevent iodine
      deficiency states].
AB  - Retrospective analysis of the prevalence of iodine-deficiency states among the
      adult population in the Moscow Central Administrative District in 2001 to 2004
      revealed an upward trend in the incidence of the major nosological entities of
      diffuse and multinodular goiter. The age distribution of iodine-deficiency
      diseases in the district is characteristic of the whole city. The prevalence of
      endocrine diseases, among which thyroid pathology is about 60%, among the
      adolescents of the district is greater than the background values (in Moscow). A
      questionnaire was used to examine 2 groups of apparently healthy (an organized
      collective body--Group A) and apparently ill (endocrinological patients--Group B)
      subjects. Nutrition rating ascertained that both groups insufficiently consumed
      iodine-containing products. At the same time, under the conditions of iodine
      deficiency, the relative risk of thyroid disease in Group A is much higher (OR =
      11.63) than in Group B (OR = 2.5). In the alternative (high and low morbidity)
      areas, the data on the sales of iodinated salt sale were analyzed and the buyers
      were questioned about its domestic use in two large supermarkets. This
      established that the district's population consumed iodinated salt little and
      showed a low awareness of its domestic use.

PMID- 20143492
TI  - [Pediatric population's health in Moscow according to the data of sociohygienic
      monitoring].
AB  - Environmental pollution has a negative impact on the health status of the
      population, on that of children in particular. In-depth developments of primary
      morbidity of childhood diseases of respiratory organs as a system that is mostly
      exposed to ambient air pollution have indicated that respiratory diseases,
      including their chronic forms, are more frequently notified in the children
      residing in the areas characterized by high levels of air pollution. Formaldehyde
      and nitric dioxide, i.e. the chemical compounds the concentrations of which
      exceed the hygienic normal values, make the greatest contribution to risk
      formation. In-depth analysis of morbidity rates in the children living in the
      areas along which the heavy-traffic motorways pass has demonstrated that chronic
      respiratory diseases are more frequently registered in these children than in
      those residing in the areas remote from the motorways. A role of social factors
      influencing the increase of the so-called alimentary-dependent diseases is shown.

PMID- 20143493
TI  - [Monitoring of the levels of metals in the bottom sediments of rivers in the
      central area of the Orenburg Region].
AB  - Among the pollutants of the biosphere, heavy metals present the greatest hazard
      since they show a high stability and toxicity and are able to migrate in the
      water ecosystems and to accumulate in the bottom sediments and hydrocoles, by
      impairing the stability of hydrobiocenoses. Chemical monitoring of the level of
      bottom sediments of rivers was made in the Central district of the Orenburg
      Region. Samples were taken at 11 stations of the Central district of the region
      and 5 stations in a district of Orenburg. The analysis of the findings indicated
      that the content of copper, zinc, cadmium, lead, chromium in the bottom sediment
      samples was not greater than the maximum permissible concentration (MPC) at any
      station and that of nickel did not exceed MPC by 1.3-2.6 times.

PMID- 20143494
TI  - [Non-invasive assessment used to evaluate the nasal and oral mucosal cytological
      status in sociohygienic monitoring].
AB  - By analyzing their own studies and the results of other studies by other
      investigators, the authors provide evidence that the noninvasive evaluation of
      the nasal and oral cytological status is one of techniques for assessing the
      health status and reflects the organism's state varying with environmental
      pollution, which enables it to be recommended for sociohygienic monitoring.

PMID- 20143495
TI  - [Prenosological approach to assessing morbidity and mortality].
AB  - The paper deals with the morbidity- and mortality-associated problem arising from
      the processes occurring in the transition period of development of new Russia. It
      points to the leading role of health care service in this process. The authors
      show the real health status of the working population, the actual state of
      affairs with the rendering primary medical care at industrial institutions.
      Measures are proposed to apply specific science-based health-promoting
      technologies adopted from Russian space medicine and called prenosological
      monitoring.

PMID- 20143496
TI  - [Impact of chemical ambient air pollution in Moscow on its population's health].
AB  - The ambient atmosphere of Moscow is appraised as unbeneficial to the health of
      the population, that of children and adolescents in particular. Motor transport
      is a powerful source of the ambient air pollution of Moscow. The average annual
      level of atmospheric pollution in 2008 is considered to be moderate. Scientific
      and-practical studies using the risk assessment methodology also suggest that the
      ambient air in Moscow is the leading habitat posing a carcinogenic and non
      carcinogenic risk to Muscovites' health.

PMID- 20143497
TI  - [Pocket guide to invasive mycoses in onco-hematologic patients].

PMID- 20143499
TI  - Proceedings of the 12th Weurman Flavour Research Symposium. July 2008.
      Interlaken, Switzerland.

PMID- 20143498
TI  - Minority participation in randomized controlled trials for obsessive-compulsive 
      disorder.
AB  - This paper reviews published randomized trials in North America to determine
      whether minority groups are underrepresented in clinical trials of OCD. A search
      of the literature produced 40 randomized trials of both adults and children with
      OCD, conducted in the U.S. and Canada from 1989 to 2009 (N = 3777). The groups
      included in this review were Caucasians/European Americans, Black/African
      Americans, Hispanic/Latino-Americans, Asian-Americans, Others, and Unknown. Of
      these, 22 of 40 trials reported ethnic/racial information or data was available
      by request. We focused on the 21 trials from 1995 to 2008 providing ethnic/racial
      information, and among those (N = 2221), 91.5% of participants were Caucasian,
      1.3% were African-American, 1.0% were Hispanic, 1.6% were Asian, 1.5% were Other,
      and 3.1% were Unknown. We conclude that minorities are underrepresented in North
      American OCD trials. Therefore, it is not known if empirically validated
      treatments are effective for these groups. Recommendations for improving
      recruitment of minorities for future studies are discussed.

PMID- 20143500
TI  - Treatment. Taking HIV medication proves difficult for many people.

PMID- 20143501
TI  - Disclosure.  Boxing referee may proceed with lawsuit against California.

PMID- 20143502
TI  - Testing.  Man given false HIV-positive results can't recover on claim.

PMID- 20143503
TI  - FDA notifications.  Pediatric dosing recommendations revised.

PMID- 20143504
TI  - FDA notifications.  ART guidelines for adults & adolescents are revised.

PMID- 20143505
TI  - Urinary profiles to assess polycyclic aromatic hydrocarbons exposure in coke-oven
      workers.
AB  - Aim of the study was the assessment of exposure of coke-oven workers to
      polycyclic aromatic hydrocarbons (PAHs) by determination of urinary profiles of
      hydroxylated and unmetabolized PAHs. Fifty-five Polish coke-oven workers were
      investigated by measurement of 12 hydroxylated metabolites of PAHs (OHPAHs) (1-,
      2-hydroxynaphthalene; 2-, 9-hydroxyfluorene; 1-, 2-, 3-, 4-, 9
      hydroxyphenanthrene; 1-hydroxyypyrene, 6-hydroxychrysene and 3
      hydroxybenzo[a]pyrene) and 13 unmetabolized PAHs (U-PAHs) (from naphthalene to
      benzo[a]pyrene), in spot urine samples collected at the end of the workshift. U
      PAHs with four or less rings were detected in all samples. In particular, median
      levels for urinary naphthalene, phenanthrene, pyrene, chrysene and
      benz[a]anthracene were 0.806, 0.721, 0.020, 0.032 and 0.035 microg/L. OHPAHs up
      to 1-hydroxypyrene were found in all samples, while high molecular-weight OHPAHs
      were always below quantification limit. Median level of 1-hydroxyypyrene was 15.4
      microg/L. In all subjects significant correlations between OHPAHs and U-PAHs were
      observed (0.27 < r < 0.70, p < 0.01). Our results suggest that both hydroxylated
      metabolites and unmetabolized PAHs in urine are useful biomarkers of exposure to
      PAHs. Moreover, the simultaneous determination of several biomarkers permits to
      obtain specific excretion profiles that might help in exposure characterization
      and in better defining the excretion patterns.

PMID- 20143506
TI  - [Laboratory methods for the diagnosis of postpericardiotomy syndrome].
AB  - The paper analyzes the diagnostic value of methods for the laboratory diagnosis
      of postpericardiotomy syndrome (PPS) in patients who have undergone open heart
      surgery. The prospective study included 63 patients, of whom 53 had the clinical
      manifestations of PPS. Ultrasensitive assay of serum procalcitonin and the
      determination of relative albumin levels in pleural and pericardial fluids are
      noted to be of high diagnostic value.

PMID- 20143507
TI  - [Algorithms of the laboratory diagnosis and monitoring of thyroid diseases in
      pregnant women: clinical laboratory aspects (a lecture)].
AB  - By taking account the recommendations of the International consensus built up by
      the Committee of the US Endocrinology Association (2007), the 2006 normative
      documents by the Ministry of Health and Social Development of the Russian
      Federation and on the basis of the their many years' clinical and pedagogical
      experience, the authors have prepared a lecture for laboratory study specialists,
      obstetricians, endocrinologists, and other physicians who are responsible for the
      management of pregnant women. Concise data on the physiology of the thyroid in
      healthy pregnant women and in those who reside in the iodine-deficiency areas are
      given. The updated data on the clinical types of gestational thyroid pathology,
      the effects of thyroid hormone deficiency and excess on a future mother, the
      placenta, and fetal growth and development are summarized. There are arguments in
      favor of and against the expediency of total and selective screening for impaired
      function of the thyroid and the general principles of the laboratory diagnosis of
      its diseases during pregnancy. Original algorithms for interpreting the
      laboratory parameters of the thyroid system during gestation in the routine
      situations of the primary diagnosis of various diseases of the thyroid in
      obstetric practice and its further monitoring during treatment are discussed.

PMID- 20143508
TI  - [Capabilities of cytological assay in the detection of metastatic lesions of the
      lymph nodes].
AB  - The study was undertaken to define the capabilities of cytological assay in the
      detection of metastatic lymph node lesions. A total of 6794 lymph nodes,
      including 5206 fine-needle biopsy specimens of and 1588 scrapes and imprints of
      the lymph nodes taken from the patients operated on at the P. A. Herzen Moscow
      Oncological Research Institute, were analyzed. Cytological specimens were stained
      using the modified Pappenheim procedure (azur-eosin mixtures). The results of the
      cytological assay were compared with those of a planned histological examination
      of the lymph nodes. Overall, the accuracy of the cytological technique was 99%;
      false-negative and false-positive results were 0.8 and 0.2%, respectively. That
      of intraoperative cytological diagnosis of metastatic lymph node lesions was
      99.2%. The cytological technique for examining the lymph nodes is a simple,
      available, and valid method of morphological diagnosis. Errors can be made in
      cases of micrometastases, sinus histiocytosis. There may be problems in the
      differential diagnosis of tumor cells and inflammatory elements.

PMID- 20143509
TI  - [Study of Legionella pneumophila strains isolated from environmental objects].
AB  - The paper presents the results of studying the biological properties of
      Legionella pneumophila strains isolated from environmental objects. Elective
      legionellosis medium (ELM) has been found to be suitable for the isolation of the
      causative agent from the starting material and to be as sensitive as CYE (Oxoid
      company) containing growth and selective additives. Polymerase chain reaction
      (PCR) with a home-produced commercial test system used to detect L. pneumophila
      DNA enables identification of the causative agent, including its species.
      Hyperimmune sera against L. pneumophila 1-7 serogroups used in slide
      agglutination and agglutination, as well as a series of co-agglutinating
      diagnosticums for legionellosis 1-7 serogroups make it possible to identify even
      the serogroups of L. pneumophilla. Comparative analysis of the virulence of L.
      pneumophila cultures in vivo and in vitro allows recommendation that practical
      laboratories should employ a simple NaCl resistance test, which can be used as a
      guide virulence test.

PMID- 20143510
TI  - The impact of Nd:YAG capsulotomy on foveal thickness measurement by optical
      coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: To measure the foveal thickness change after Nd:YAG
      laser capsulotomy by optical coherence tomography (OCT). PATIENTS AND METHODS:
      Fifty-four eyes of 54 patients who had posterior capsule opacification underwent
      Nd:YAG laser capsulotomy. OCT of the foveal region was performed preoperatively
      and postoperatively (on days 1 and 7 and months 1, 3, 6, and 12). The
      preoperative and postoperative measurements were compared. RESULTS: The foveal
      thickness did not significantly change in the first year after laser treatment.
      Cystoid macular edema developed in only 1 patient (2%). Patient age and gender,
      time between surgery and laser capsulotomy, total laser shots, total laser
      energy, or mean laser energy per shot did not affect the foveal thickness.
      CONCLUSION: Foveal thickness does not change in the first year after Nd:YAG laser
      capsulotomy, as determined by OCT.

PMID- 20143511
TI  - [Ventricular rhythm mimicking preexcitation].

PMID- 20143512
TI  - [Is it practical to use measurement of BNP and NT-proBNP levels in patients with
      acute coronary syndromes?].

PMID- 20143513
TI  - [Trials for prevention of recurrent aortic-coronary occlusion of venous grafts].

PMID- 20143514
TI  - [The value of thoracic fluid determination - hopes and limits].

PMID- 20143515
TI  - [Personal quality of life in cardiac patients].

PMID- 20143516
TI  - Dilated cardiomyopathy in the postgenomic era.

PMID- 20143517
TI  - [Interruption of slow ventricular tachycardia below the detection rate of
      implantable cardioverter-defibrillators].

PMID- 20143518
TI  - [Is it necessary to fool the cardioverter-defibrillator?].

PMID- 20143519
TI  - [The effect of fluvastatin treatment on the occurrence of perioperative events in
      a group of patients subjected to vascular surgery].

PMID- 20143520
TI  - [DECREASE III study - drop in and for statins as prevention for perioperative
      threatened patients].

PMID- 20143521
TI  - Fight against leprosy no longer about the numbers.

PMID- 20143522
TI  - [Neutral and acid glycolipids in the brain in the presence of ischemia and during
      antioxidant treatment].
AB  - The content of lipid peroxidation products and the metabolism of gangliosides and
      galactosylceramides in brain tissue were studied in the presence of ischemia and
      when an agent containing nicotinic acid and cysteine is administered. The above
      agent was found to have an antioxidative effect that was evident in the lower
      levels of lipid peroxides and in the normalized qualitative and quantitative
      content of galactosylceramides and gangliosides.

PMID- 20143523
TI  - [Exchange of biometals in myocardial infarction: a clinical and experimental
      study].
AB  - The paper presents the results of studying trace elements (Zn, Cu, Fe, and Mg) in
      60 patients with myocardial infarction and Wistar normotensive and NISAG
      hypertensive rats. Clinical and experimental correspondences of the impaired
      blood trace element composition have been found in patients and experimental
      animals and the mechanisms of these disorders.

PMID- 20143524
TI  - [The specific features of kallikrein-kinin system functioning in reproductive
      aged women with hypertensive disease].
AB  - The performed clinical and biochemical study evaluated the specific features of
      kallikrein-kinin system (KKS) functioning in reproductive-aged women in health
      and in early hypertensive disease. The major molecular mechanism responsible for
      early hypertensive disease in young women was shown to be activation of the renin
      angiotension-aldosterone system due to enhanced kininogenesis. These alterations
      in KKS performance were followed by the structural changes in vascular wall
      connective tissue, which was evident in endothelial dysfunction and which was a
      morphological basis for development of the major clinical signs of hypertensive
      disease.

PMID- 20143525
TI  - [Role of myocardial hypoxic lesions in the development of heart failure in the
      presence of pancreonecrosis].
AB  - Experimental pancreonecrosis was simulated in 50 Wistar rats. Following 24 hours,
      the mechanisms of cardiac lesion were revealed, by applying a model of the
      perfusion isolated heart by the method described by Fallen et al. and by
      estimating the force and velocity parameters of cardiac contractility. Activation
      of free radical processes and hypoxia were ascertained to be the most important
      pathogenetic factors of pancreatogenic heart failure, which was substantiated by
      the results of the investigations on rats that had received the energy-rich agent
      reamberin in a dose of 10 mg/kg before simulation of pancreonecrosis.

PMID- 20143526
TI  - [Recovery of the cardiovascular system and the state of its autonomic regulation
      after prior long hemorrhagic shock during vaccination with tetanus and diphtheria
      anatoxins].
AB  - Tetanus anatoxin was shown to have a stimulant effect on the cardiovascular
      system and its autonomic regulation, which produced a longer posthemorrhagic
      survival in the controls with the least pronounced dystrophic changes in the
      myocardium. Prior vaccination with diphtheria anatoxins was found to promote
      animals' survival, by reducing reperfusion injury in the presence of long-term
      systemic hypoperfusion, early exhaustion of sympathetic autonomic cardiac rhythm
      regulation, and myocardial dystrophic and necrobiotic changes resulting in the
      development of cardiosclerosis.

PMID- 20143527
TI  - [Tissue morphological changes in experimental anthrasilicosis].
AB  - Anthrasilicosis was experimentally stimulated by inhaled inoculation. Various
      degrees of morphological changes were detected depending on the time of
      inoculation and the stage of the pathological process: the changes were early
      observed in the lung and liver, which became worse by week 12 of inoculation;
      from week 6 these were in the heart and kidney, which was indicative of systemic
      disorders in response to dust exposure.

PMID- 20143528
TI  - [Experimental rationale for the use of enterosorbents in acute ethanol
      intoxication].
AB  - The experiment on 83 rats has provided a rationale for the use of enterosorbents
      in acute ethanol intoxication. Polysorb reduces the halflife of ethanol, recovers
      physical fitness in the animals with acute poisoning. The enterosorbents
      polysorb, litovit, and sapropel have been found to have a corrective effect on
      the level of the major plasma antioxidant ceruloplasmin in acute ethanol
      intoxication. Enterosorbents are an effective detoxifying agent in this
      condition. Examining the mechanisms of toxic action of ethanol allows the most
      expedient treatment policy to be substantiated in acute poisonings.

PMID- 20143529
TI  - [Development of endothelial dysfunction in sex hormone deficiency].
AB  - The review of literature deals with the implication of estrogen deficiency in the
      development of endothelial dysfunction and its related cardiovascular diseases.

PMID- 20143530
TI  - [To the role of basic education in the creation of a specialist].

PMID- 20143531
TI  - [Antiangiogenic therapy for choroidal neovascularization induced by age-related
      macular degeneration (preliminary communication)].
AB  - Specific antiangiogenic therapy for exudative age-related macular degeneration
      (AMD) aims at suppressing the growth of choroidal neovascularization.
      Bevacizumab, an antibody to vascular endothelial growth factor, is one of the
      agents that specifically inhibit angiogenesis. The results of using bevacizumab
      in choroidal neovascularization induced by AMD are analyzed. Bevacizumab was
      administered into the vitreous body of 56 patients (60 eyes) in a dose of 1.25
      mg; its injections were repeated if the need arose in disease recurrence. The
      follow-up time was 6 to 12 months. Following 6 months, visual preservation not
      below the baseline level was noted in 86% of cases; in this period a significant
      visual improvement was stated in 46% of cases. Fluorescence angiography showed
      decreased dye leakage in most cases, which correlated with the lower retinal
      thickness revealed by optical coherence tomography. There were no serious
      complications. Intravitreal administration of bevacizumab is the method of choice
      in treating exudative AMD and requires further investigation.

PMID- 20143533
TI  - [Transpupillary thermotherapy in the treatment of recurrent and residual
      choroidal melanomas: preliminary results].
AB  - Thirty-eight patients (16 males and 22 females) with recurrent and residual
      choroidal melanomas who had undergone brachytherapy were followed up. The
      indication for transpupillary thermotherapy (TTT) was an active residual tumor
      (36 patients) and recurrent melanoma (2 patients). The follow-up interval between
      brachytherapy and TTT was 10 to 127 months. TTT using a diode laser was performed
      on a Nidek DC 3300 device at a wavelength of 810 nm. The mean tumor prominence
      prior to TTT was 1.9 mm (range 1 to 3.5 mm), its mean diameter was 8.6 mm (range
      4-14.5 mm). Twenty patients were observed over time. The follow-up time after TTT
      was 3 to 15 months. After the first session of TTT, a positive effect was
      observed in 15 patients. In 9 patients, the effect was inadequate, which required
      additional sessions of TTT. Among the early TTT complications, there were
      superficial petechial hemorrhages, macular edema, exudative retinal detachment
      above the tumor. Treatment resulted in no complications in 18 patients. Late
      metastases were seen in none patients. Our investigations have indicated that TTT
      is a highly effective treatment for recurrent and residual uveal melanomas, which
      provides complete tumor resorption in 29% of the patients.

PMID- 20143532
TI  - [Optical coherence tomography in the diagnosis of retinal alterations in the
      presence of pigmented choroidal tumors].
AB  - Optical coherence tomography (OCT) was used to examine 33 patients (33 eyes) with
      choroidal melanoma and 39 patients (39 eyes) with choroidal nevus. The magnitude
      of changes in the retina and its pigment epithelium above the pigmented choroidal
      neoplasms was found to be largely in proportion to their sizes. When primarily
      detected, choroidal melanomas had larger sizes and were significantly more
      frequently attended by neuroepithelial detachment, retinal edema, and evident
      impairments in the normal architectonics of the retina and its pigment epithelium
      above the tumor, neuroepithelial detachment in the foveal area, and these tumors
      tended to show a higher rate of pigment epithelial detachments above the tumor
      and foveal edema. However, in the presence of small neoplasm sizes (from 1 mm,
      but less than 2 mm), the patients with choroidal melanomas were observed to have
      more frequently neuroepithelial detachment and to tend to have a higher rate of
      retinal edema above the tumor.

PMID- 20143534
TI  - [Ophthamoergonomic evaluation of the efficiency of intraocular phacolenses versus
      contact lenses for correction of high-grade myopia].
AB  - The paper gives the results of comparative assessment of ophthalmoergonomic
      indicators of the visual system in patients with high-grade myopia after contact
      correction and within 12 months after phacitic intraocular lens (IOL)
      implantation. A considerable increase in the level of visual analyzer performance
      was achieved after surgical correction. The found positive changes in visual
      analyzer performance after phacitic intraocular lens versus contact correction
      are explainable in the context of physiological optics by the formation of the
      optimal ocular cornea--phacitic IOL--lens system that ensures great functional
      reserves for visual perception as a whole as compared with the optical contact
      lens--cornea--lens system.

PMID- 20143535
TI  - [Cytokine therapy in the regulation of corneal reparative processes: an
      experimental and clinical study].
AB  - Cytokine monotherapy with Superlymph used in combination with the keratoprotector
      Applicoll in the treatment of superficial corneal layer defect resulted in
      rapidly alleviated inflammatory reactions, accelerated reparative processes, more
      qualitative epithelial defect recovery, by forming a finer scar, without opacity
      whereas the traditional treatment led to long-term healing and keratoleukoma in
      an experiment. The use of cytokine therapy with Superlymph in the complex
      treatment of corneal injuries and inflammation in children promoted a prompt and
      stable arrest of a local inflammatory process, accelerated epithelization,
      reduced opacity intensity, higher visual acuity, and shorter treatment.

PMID- 20143536
TI  - [Local ocular immunity parameters in chronic rhino- or odontogenic infection].
AB  - Thirty-four patients with foci of chronic rhino- or odontogenic infection were
      examined. All the patients underwent physical examination, biochemical blood
      analysis, immunological test for immunoglobulins A, G, and M, circulating immune
      complexes, leukocyte migration inhibition test with phytohemagglutinin, Con A,
      with antigens of the retina, vitreous body, iris, and lens, scrapes from the
      dentogingival pocket, conjunctival and nasal cavities for Chlamydia, followed by
      direct immunofluorescence, polymerase chain reaction, and culture. Chronic rhino-
      or odontogenic infection foci impair local ocular immunity in ophthalmologically
      healthy patients. The foci of chronic rhinogenic infection cause more pronounced
      changes in systemic and local ocular immunity than those of chronic odontogenic
      infection. In half the patients with chronic rhino- or odontogenic infection
      foci, Chlamydia are detectable in the oral, nasal, and ocular mucosae, which
      suggests that there is generalized infection and there is a need for complex
      sanitation of the body. Isolated local treatment for Chlamydia infection is not
      promising.

PMID- 20143537
TI  - [The levels of cortisol and glycosaminoglycans in patients with uveitis in
      rheumatic diseases].
AB  - The serum levels of cortisol and glycosaminoglycans (GAG) were studied in
      patients with uveitis in rheumatic diseases (RD). Among the patients with this
      pathology, there was a more preponderance of persons with low cortisol levels. In
      acute uvitis in the presence of RD, the mean serum content of this hormone was
      significantly lower than that in infectious and idiopathic uveitis. In RD,
      uveitis ran well with positive changes in the serum levels of cortisol, which
      increased during treatment. Its poor course was observed when the low content of
      cortisol remained or decreased still further. GAG exchange in uveitis patients
      with RD changed: there was an inverse correlation between the level of hyaluronic
      acid and that of cortisol (r = -0.7994; p = 0.031); the same correlation was
      found in males between the concentration of summary GAG and that of cortisol (r =
      -9832; p = 0.003) and chondroitin sulfate (r = -9965; p = 0.001).

PMID- 20143538
TI  - [Acute uveitis in nonspecific ulcerative colitis].
AB  - The paper describes a case of a type of the manifestation of aveitis associated
      with an exacerbation of nonspecific ulcerative colitis. Ultrasound diagnostic
      techniques, such as ultrasound biomicroscopy and B-scanning, evaluate the uveal
      tract that can no longer be imaged, by using the traditional examination methods.
      These methods extend diagnostic capabilities and permit an objective monitoring
      of the status of a patient.

PMID- 20143539
TI  - [Study of stereoscopic visual acuity, by using the color anaglyph method].
AB  - A method is proposed to study stereoscopic visual acuity (SVA) by means of the
      test objects designed by the computer program Adobe Photoshop CS 2 (version 9,
      2005). Each test object contains 3-4 silhouette figures made on the principle of
      color anaglyphs with varying degrees of transverse disparity. The capacity of an
      examinee of correctly showing on the display screen the sequence of the layout
      for the figures in depth with a minimal disparity determines its SVA. The authors
      propose to consider a disparity of 30 seconds of angle as a unit of SVA. The
      results of SVA examination using the proposed method (when the same object is
      demonstrated) do not depend on the site of figures on the screen and on the
      distance between the examinee and the monitor.

PMID- 20143540
TI  - [To the treatment of recurrent pterygium].
AB  - The author proposes a surgical technique for pterygium, which involves excision
      of the latter from apex to base, removal of a conjunctival growth area by
      wrapping it with the remainder above the pterygial body towards the interior
      angle of the eyelids, capture of the musculus rectus internus on a traction
      suture for thorough evacuation of the interior angle of the eyelids from the
      pterygium and for convenient scleral graft fixation, and closure of a formed
      conjunctival defect with an Ufaplant ophthalmological graft, by making additional
      cuts upon its surface for vascularization. A total of 87 patients with recurrent
      pterygium were operated on, by applying the proposed technique. High functional
      and cosmetic results were achieved in all cases; no recurrences were observed.

PMID- 20143541
TI  - [Eye fundus autofluorescence technique in the early diagnosis of age-related
      macular degeneration].
AB  - Autofluorescence (AF) of the eye fundus is one of the most promising studies. AF
      provides specific molecular information on the retinal pigment epithelium and
      enables one to diagnose early phenotypic changes that are predictors for
      progression of age-related macular degeneration. Many investigations have
      demonstrated that AF is a valuable clinical technique that should be improved in
      order to have information accessible to a patient on the diagnosis and prediction
      of age-related macular degeneration.

PMID- 20143542
TI  - [The state of epithelial cells and tissues exposed to an electromagnetic field].
AB  - Based on the analysis of 56 references available in the Russian and foreign
      literature, the authors provide information on the mechanism of exposure of
      tissues and cells to electromagnetic fields. The electromagnetic filed can
      regulate the orientation of epithelial cell division and cause their directional
      movement. There are different explanations for such movement. This property may
      be used in ophthalmology to control corneal epithelial regeneration. This problem
      has been inadequately investigated.

PMID- 20143543
TI  - [Surgery for retinal internal limiting membrane (communication 1)].
AB  - The review of literature describes the structure and function of the internal
      limiting membrane (ILM) of the retina, shows indications for its removal, the
      mechanisms of action of and the efficiency of ILM peeling in various macular
      pathologies, as well as ILM removal techniques.

PMID- 20143544
TI  - [Surgery for retinal internal limiting membrane (communication 2)].
AB  - The paper reviews specific complications of conventional peeling of the internal
      limiting membrane (ILM) of the retina in various macular pathologies. It also
      considers the promising directions of development of ILM surgery, including
      enzymatic lysis and femtosecond laser ablation of the ILM.

PMID- 20143545
TI  - [Diagnosis of circulatory disorders in the optic nerve in primary open-angle
      glaucoma. Communication 1. The circulatory system in the orbital portion of the
      optic nerve and its anatomic and topographic features].
AB  - The review analyzes the implication of ischemia in the pathogenesis of primary
      open-angle glaucoma. It gives the opinions of leading Russian and foreign
      specialists who deal with this problem. The basic studies of the morphology of
      the optic nerve head and its circulatory system are assessed. The specific
      features of the structure of the orbital arterial system based on the types of
      ocular arterial branching via formation of intraocular circulation are compared.

PMID- 20143546
TI  - [Diagnosis of circulatory disorders in the optic nerve in primary open-angle
      glaucoma. Communication 2. New technologies for the imaging and evaluation of the
      circulatory system in the optic nerve head].
AB  - The review details the basic principles of the optic nerve head circulation. It
      analyzes the diagnostic capacities of various study methods that are both
      traditional and proposed and tested in the past decade. The results of Russian
      and foreign specialists' studies based on Doppler ultrasound study of the ocular
      artery, short posterior ciliary arteries, and central retinal artery are given.

PMID- 20143547
TI  - [Planning advanced research in the framework of goal-oriented scientific programs
      and their role in the development of cardiovascular surgery in the Russian
      Federation].
AB  - The role of goal-oriented scientific programs in the development of
      cardiovascular surgery is illustrated including its early and mature periods.
      Conceptual planning of such programs and their importance for the elaboration of
      new promising methods of diagnosis and surgical treatment of cardiovascular
      pathology are analysed in the context of organization of modem high-technology
      cardiosurgical care.

PMID- 20143548
TI  - [Progress in cardiovascular surgery: new analytical, experimental, and
      technological approaches].
AB  - Blood flow in heart and main vessels is a self-organizing eddy flow described by
      Kiknadze-Krasnov's non-stationary hydrodynamic equations. Their exact solutions
      are applicable to simulation of blood circulation in normal and pathological
      conditions, quantitative evaluation of efficiency of surgical treatment of
      cardiovascular diseases, and designing implantable devices for cardiovascular
      surgery to support physiological blood flow structure. An essentially new all
      flow three-leaflet CorBit artificial heart valve from pyrolyitic carbon has been
      proposed to maintain physiological blood flow with minimal regurgitation and
      transvalvular pressure gradient. The CorBit valve allows to normalize hemodynamic
      parameters soon after implantation. Also, manufacture is underway of a wide range
      of original stented and stentless bioprostheses of heart valves and valve
      containing BioLab conduits from allogenic and xenogenic biological tissues.
      BioLab bioprostheses are currently widely used to treat complicated congenital
      and acquired forms of cardiopathology.

PMID- 20143549
TI  - [The history of Wolf-Parkinson-White syndrome and evolution of surgical methods
      for its management].
AB  - Wolf-Parkinson-White syndrome (WPW syndrome) affects roughly 1% of the
      population. It usually occurs in subjects with normal heart function but may
      combine with congenital cardiac failure and cardiomyopathy. Paroxysmal
      tachycardia is recorded in 40-80% of he WPW patients, largely in the form of
      reciprocal tachycardia related to circulation of excitation in the
      atrioventricular junction and Kent's bundle. Development and improvement of
      surgical methods for the management of supraventricular tachycardia became
      possible with the advent of transcatheter registration of electrical activity in
      different heart regions and programmed heart stimulation techniques. Catheter
      assisted methods for the treatment of cardiovascular disorders including
      arrhythmia have been extensively used in recent decades. Transvenous fulguration
      is one of them replaced at present by radiofrequency ablation (RFA). The
      discovery of WPW syndrome made possible a new approach to the the problem of
      sudden death in young age. Treatment of this syndrome by RFA of additional
      atrioventricular junction in the last 20 years permitted not only to manage the
      syndrome itself but also to ensure practically complete recovery of the patients.

PMID- 20143550
TI  - [Possible complications of catheter ablation of atrial fibrillation].
AB  - Atrial fibrillation (AF) is the commonest form of disturbed cardiac rhythm.
      Hundreds of thousands of AF ablations are annually performed worldwide using
      different energy sources. One of the most popular methods is radiofrequency
      catheter ablation (RFA). This treatment is fraught with various risks being a
      highly complicated technical procedure. This review paper presents data on the
      most frequent complication of RFA, their frequency, causes, diagnosis, treatment
      and prevention. Much attention is given to the recognition and prevention of
      possible complications.

PMID- 20143551
TI  - [Hybrid surgical palliation for hypoplastic left heart syndrome in newborn
      infants].
AB  - Hybrid surgery for the treatment of hypoplastic left heart syndrome was
      undertaken in 19 newborn infants from December 2007 to January 2009. An original
      method was used with the approach from posterolateral thoracotomy bypassing
      pulmonary arteries from the transverse pericardial sinus. The survival rate was
      84%.

PMID- 20143552
TI  - [Results of bidirectional cavapulmonary shunt operation without cardiopulmonary
      bypass in children with complicated congenital heart defects during the first
      year of life].
AB  - The authors present results of bidirectional cavapulmonary shunt operation
      without cardiopulmonary bypass for the treatment of complicated congenital heart
      defects. Temporary blood shunting during surgical intervention enables
      cavapulmonary anastomosis to be created without making resort to artificial
      circulation (AC) and limitation on the time of superior vena cava occlusion. The
      proposed method is free from additional risks and excludes negative effects of
      AC. It allows for conversion to AC as appropriate at any time during surgery in
      the "bypass stand-by" regime.

PMID- 20143553
TI  - [Modern approaches to surgical treatment of patients with complicated and
      combined forms of coronary heart diseases].
AB  - The incidence of atherosclerotic lesions in coronary arteries combined with other
      vascular problems has been increasing during the last years. Hence, a rise in the
      number of patients with coronary heart disease, candidates for surgical
      myocardial revascularization. This paper reviews the history of surgical
      treatment of combined lesions of coronary and peripheral arteries and presents
      original criteria developed in A N Bakulev Research Centre of Cardiovascular
      Surgery for the choice of surgical strategy to treat multifocal atherosclerosis
      and postinfarction left ventricular aneurysm.

PMID- 20143554
TI  - [Comparative evaluation of efficacy of intracoronary shunts in minimally invasive
      myocardial revascularization].
AB  - Intracoronary shunts (IS) are devices for maintaining distal coronary blood flow
      when placing anastomoses with coronary arteries. The use of IS ensures functional
      and electrical stability of myocardium during its revascularization on the
      working heart. There are reports of endothelial damage by IS leading to
      dysfunction of coronary shunts. This study compares 208 patients with and without
      IS. Results of surgery were evaluated during hospitalization period. The groups
      were matched for initial clinical and instrumental characteristics and the number
      of shunt placements. It was shown that minimally invasive myocardial
      revascularization with the use of IS when placing distal anastomoses has a number
      of advantages over similar surgery without IS, viz. smaller degree of
      intraoperative myocardial lesion, blood loss, and frequency of postoperative
      complications along with enhanced stability of intraoperative hemodynamics.

PMID- 20143555
TI  - [Alternative methods of myocardial revascularization].
AB  - The study was designed to analyse results of alternative methods of myocardial
      revascularization in "no-option patients" to whom direct revascularization is not
      indicated. Over 600 cases were treated with the use of transmyocardial laser
      revascularization (TMLR), angiogenic factors (VEGF, alpha-ECGF), and cellular
      therapy. It was shown that TMLR is a safe and efficacious procedure increasing
      perfusion and normalizing myocardial metabolism. It eliminates angina and
      improves quality of life of the patients. Single bolus administration of
      angiogenic factors alone does not stabilize perfusion and patients' condition.
      The use of stem cells provokes the growth of new vessels and promotes restoration
      of viable myocardium via stimulation of angiogenesis. However, mesenchymal stem
      cells do not contribute to scar reparation and are inefficient in patients with a
      critical mass of cicatrically-altered myocardium.

PMID- 20143556
TI  - [Correction of ischemic atrioventricular insufficiency as a component of surgical
      remodeling of post-infarction heart in patients with ischemic dilatation
      cardiomyiopathy].
AB  - Patients with ischemic dilatation cardiomyopathy are most difficult to control
      symptoms of cardiac insufficiency (CI). Analysis of survival, results of cardiac
      chamber remodeling, and severity of CI in 192 patients showed that the optimal
      outcome of the treatment is on the average achieved in case of surgical
      revascularization combined with correction of ischemic atrioventricular
      insufficiency.

PMID- 20143557
TI  - [The use of assisted circulation in cardiosurgical clinic].
AB  - The first experience with the use of different artificial circulation systems for
      the treatment of critical cardiac insufficiency in A. N. Bakulev Research Centre
      of Cardiovascular Surgery is described. The authors analyse their efficiency,
      indications for use, possible causes of complications and fatal outcome.

PMID- 20143558
TI  - [Stroke in the clinical practice of a therapist].
AB  - The stroke resulting in serious neurologic deficit is the third most frequent
      cause of death and loss of working ability. In 60-65% of the cases, it is
      provoked by atherothrombosis located in aortic arch, common and internal carotid
      arteries. Thromboembolism of cerebral vessels originating in heart cavities is
      responsible for 15-18% of the cases. Stroke prevention is an interdisciplinary
      problem encountered not only by neurologists but also by many other physicians. A
      major preventive tool for the stroke is healthy lifestyle while therapy with
      antithrombotic drugs (antiaggregants, oral anticoagulants) is the main component
      of secondary prevention. The choice of therapy depends on the cause and degree of
      stroke.

PMID- 20143559
TI  - [Chronic hepatitis C: etiology, pathogenesis, treatment].
AB  - Chronic hepatitis C (CHC) is the major cause of chronic hepatic pathology,
      cirrhosis, and hepatocellular carcinoma. CHC affects approximately 3.2 mln
      Americans. The commonest routes of CHC transmission are drug injections, blood
      transfusion, and sexual contacts (in this order). CHC is frequently an
      asymptomatic infection. Jaundice occurs only in one third of the cases with acute
      infection. Cirrhosis develops in 20-30% of the patients with chronic infection
      during 20 years. Cirrhosis eventually evolves into hepatocellular carcinoma in 1
      4% of the patients per year.

PMID- 20143560
TI  - [The role of postprandial hyperglycemia in the development of cardiovascular
      diseases in type 2 diabetes mellitus].
AB  - The aim of this clinico-epidemiological study was to elucidate the role of
      postprandial hyperglycemia (PH) and high glucose level 2 hours after glucose load
      in the development of cardiovascular disorders (CDD) in patients with type 2
      diabetes mellitus and in the general population. Medical interventions to reduce
      PH decrease the risk of CDD. Pathophysiological studies show the involvement of
      oxidative stress in pathogenesis of CDD in cases with PH. Acute hyperglycemia
      increases heart rate and arterial pressure, disturbs myocardial perfusion and
      contractility, causes endothelial dysfuncton and atherosclerosis. The following
      preparations are recommended to subjects with DM2 and PH: alpha-glucosidase
      inhibitors, glynides, ultrashort-acting insulin analogs, dipeptidylpeptidase-4
      inhibitors, exenatide (incretin mimetic).

PMID- 20143561
TI  - [Correction of antioxidative state during statin therapy of coronary heart
      disease with dyslipidemia].
AB  - Treatment with simvastatin (vasilip) at a daily dose of 20 mg combined with
      conventional cardiac therapy was given for 3 months to 132 patients with coronary
      heart disease and postinfarction cardiosclerosis with dyslipidemia. Activity of
      tissue and plasma antioxidative enzymes increased in 60% of the patients and
      decreased in 40%. Treatment with antioxidants 2-ethyl-6-methyl-3-oxypiridine
      succinate (mexidol) and ubichinon (cudesan QIO) improved antioxidative status of
      the patients and clinical picture of cardiac pathology.

PMID- 20143562
TI  - [Effect of lipid metabolism disturbances on electrophysiologic heart remodeling
      in patients with hypertensive disease].
AB  - The aim of the study was to evaluate effect of disturbed lipid metabolism on
      dispersion of QT interval, signal-averaged ECG characteristics, and cardiac
      rhythm variability as indicators of electrophysiological remodeling of myocardium
      in patients with HD. The study included 111 patients aged 30-73 (mean 51.4 +/-
      10.7) years with stage I-II HD. All of them were examined by 12-lead ECG and high
      resolution ECG with the analysis of late atrial (LAP) and ventricular (LVP)
      potentials. Cardiac rhythm variability (CRV) was evaluated. Analysis of standard
      ECG parameters depending on lipid metabolism revealed significantly higher
      dispersion of corrected QT interval in patients with hypercholesterolemia. High
      resolution ECG showed LAP in 16 (25%) patients with hypercholesterolemia compared
      with 11% among patients with normal serum cholesterol (chi2 = 2.8; p = 0.042).
      LVPs were documented in 41, 34, 31, and 26% of the patients with high, moderately
      elevated, low, and normal serum cholesterol respectively. The difference was
      confirmed by respective changes of certain parameters of high-resolution ECG in
      the same patients.

PMID- 20143563
TI  - [Cerebral circulation in chronic hypertensive encephalopathy].
AB  - Cerebral blood supply was studied in 123 patients with stage III hypertensive
      encephalopathy (HE) in the absence of occlusion of main head arteries. Duplex
      scanning was used to measure blood flow rate in common carotid (CCA), vertebral
      (VA) and medial cerebral (MCA) arteries. Cortical cerebral blood flow (CBF) was
      measured by single-photon emission CT using 99mTc- ceretec. Normal and stable
      blood flow in CCA and VA was documented at all HE stages whereas it decreased in
      MCA of patients with HE II-III. Cortical CBF in frontal and parietal segments in
      HE II-II was higher than in HE I (p < 0.05). These findings suggest impaired
      subcortical perfusion and correlation of the discrepancy between cortical and
      subcortical blood supply with the severity of HE. Leukoaraosis is an indicator of
      hypoperfusion.

PMID- 20143564
TI  - [Modification of coronary sinus in patients with chronic cardiac insufficiency].
AB  - Both venous and arterial beds undergo a number of morphofunctional changes in
      patients with cardiovascular pathology, but they rarely attract attention of
      researchers. The available data indicate that the cardiac venous system (CVS)
      plays an important role in the development of chronic cardiac insufficiency (CCI)
      and dictate the necessity of its in-depth studies. We examined CVS in 160
      patients by Doppler echo-CG and in 41 ones by spiral CT. The patients were
      allocated to 3 groups depending on the stage of CCI (IIA, IIB and III stages, III
      IV functional class). The state of their coronary sinus (CS) was compared with
      that of healthy subjects. The state of CS varied considerably depending on the
      stage of CCI. It is concluded that patients with CCI need their CVS to be studied
      by all available methods.

PMID- 20143565
TI  - [The scope of clinical applications of noninvasive methods for the assessment of
      liver fibrosis results of orginial studies in a multi-field hospital].
AB  - Potential and limitations of non-invasive methods for the evaluation of hepatic
      fibrosis are discussed (hepatic elastography, fibrotest, ultrasound
      dopplerography of portal vessels). Each non-invasive method was assessed in terms
      of threshold values it provides for the characteristic of successive stages
      ofhepatic fibrosis. The data obtained were used to develop the optimal algorithm
      for the diagnosis of hepatic fibrosis in patients with chronic viral liver
      infection.

PMID- 20143566
TI  - [Structural and functional features of the left ventricle in patients with
      hypertensive form of chronic glomerulonephritis with preserved kidney function].
AB  - Remodeling and changes of left ventricular (LV) function objectively characterize
      effects of arterial hypertension (AH). However, structural and functional state
      of LV in patients with AH, chronic glomerulonephritis (CGN), and preserved renal
      function remains virtually unexplored. It was studied by Doppler echo-CG in 136
      patients with hypertensive form of CGN to reveal LV hypertrophy, remodeling,
      systolic and diastolic function. LV hypertrophy was shown to develop starting
      from stage 2 AH when it had concentric shape compared with dilatation eccentric
      one in patents with stage 3 AH. In either case systolic function of LV decreased.
      Diastolic dysfunction was diagnosed in all patients with AH and CGN.

PMID- 20143567
TI  - [Morphological and immunohistochemical characteristics of oral mucosa in patients
      with inflammatory intestinal disorders].
AB  - The aim of the work was to study morphological and immunological characteristics
      of oral cavity in patients with Crohn's disease and ulcerative colitis. The group
      of 40 patients aged 18-64 yr included 30 with Crohn's disease and 10 with
      ulcerative colitis. They were examined in clinical, endoscopic, morphometric, and
      immunohistochemical studies. Crohn's disease was shown to be associated with
      inflammatory processes in the gastrointestinal tract and oral mucosa; in
      ulcerative colitis, these processes were confined to the colon. It is supposed
      that inflammation of oral mucosa may be regarded as a separate phenotypic
      characteristic of Crohn's disease localization with definitive differential
      diagnostic and prognostic criteria.

PMID- 20143568
TI  - [Alternative and complementary medicine. Past, present, future. Part 1].
AB  - Part 1 highlights general problems of alternative and auxiliary medical treatment
      and presents the evidence base of dietetic nutrition of patients with
      cardiovascular diseases. Many studies demonstrated effect of dietetic factors on
      arterial pressure (AP). It drops with a decrease in body weight due to rational
      nutrition, reduced salt and alcohol consumption, elevated intake of potassium,
      and compliance with DASH regimen. Effect of other factors influencing AP is
      either dual, less significant or inexplicable. Reduction of the burden of
      cardiovascular diseases requires the development of new strategies including
      dietary treatment.

PMID- 20143569
TI  - [Immune status of patients with idiopathic thrombocytopenic purpura in the
      delayed post-spelenectomy period].
AB  - The aim of the work was to evaluate results of the treatment of idiopathic
      thrombocytopenic purpura (ITP) in terms of relationship between immunity and
      clinical compensation of the disease, changes in the immune status of patients
      with its long duration, causes of long-term success or failure of splenectomy
      (SE) compared with cases treated by glucocorticoids alone. The study included 76
      patients with chronic ITP of less than 1 year duration divided into 2 groups. 36
      of them underwent SE and 40 were given prednisolone therapy. Examination included
      identification of lymphocyte subpopulations by flow cytometry, besides IgA, IgM,
      and IgG during exacerbation and remission (absence of hemorrhagic syndrome). It
      was shown that the major factors exerting negative effect after SE were elevated
      levels of total T-lymphocytes and their subpopulations (CD4+ and CD8+, especially
      T-helpers), B-lymphocytes, and IgM. Lower efficiency of conservative therapy with
      prednisolone was due to the absence of decrease in the absolute number of T
      lymphocytes and changes in IgM.

PMID- 20143570
TI  - [Differential therapy of arterial hypertension based on the analysis of cardiac
      rhythm variability].
AB  - The study was designed for spectral analysis of cardiac rhythm variability (CRV)
      in practically healthy subjects and patients with AH. Classification of
      oscillatory cardiac rhythm activity is proposed based on CRV characteristics in
      four frequency ranges, viz. ultralow frequency (ULF), very low frequency (VLF),
      low frequency (LF), and high frequency (HF). Three types of CRV are distinguished
      (low, medium, and high-amplitude). Differential hypotensive therapy is
      recommended depending on the initial CRV level. Patients with AH and markedly
      narrowed CRV spectrum should be treated with beta-adrenoblockers, those with
      moderate and elevated CRV with ACE inhibitors and calcium antagonists
      respectively. Modern computer technologies for the analysis of slow-wave events
      in blood circulation may be used to evaluate regulatory process and thereby to
      facilitate the choice of adequate therapy.

PMID- 20143571
TI  - [Familial transthyretin amyloidosis].
AB  - A case of familial transthyretin amyloidosis with TTR Cys 114 gene polymorphism
      is described (first in Russia and third in the world). The clinical picture of
      the proband was dominated by symptoms of autonomous polyneuropathy (orthostatic
      hypotension, erectile dysfunction, diarrhea, tachycardia, foot dyshydrosis) and
      of somatic nerve lesions (dumbness, impaired surface and deep sensitivity in the
      limbs). The patient presented with vitreous body opacity, disturbed eye
      movements, lateralized sensory symptoms, and difficulty of speech (baryphonia).
      Electromyographic quantitative autonomous testing and measurement of evoked
      sympathetic skin potentials confirmed affection of peripheral nerves. Heart
      ultrasound revealed restrictive amyloid cardiopathy. Histological analysis showed
      amyloid deposition in the intestines and sural nerve. The proband, his daughter,
      brother (monozygous twin), and brother's daughter had mutant TTR Cys 114 gene.
      The brother also had amyloid deposits in the absence of clinical signs of the
      disease. Analysis of familial medical history demonstrated autosomal dominant
      inheritance of this mutation in 4 generations. Its possible origin and clinical
      features of the disease are discussed.

PMID- 20143572
TI  - [Surgical treatment of post-infarction left ventricular aneurysm complicated by
      thromboendocarditis].
AB  - This paper reports the result of surgical treatment of a patient with
      hemodynamically significant post-infarction left ventricular aneurysm spreading
      over the apex, anterolateral wall of the left ventricle, and a major part of
      interventricular septum complicated by thromboendocarditis.

PMID- 20143573
TI  - [Comments on the article of Dimov A. S. "Crisis of deontology: methodological
      aspects"].

PMID- 20143574
TI  - On cobalt-chrome frameworks in implant dentistry.
AB  - BACKGROUND: Cobalt-chrome (CoCr) alloys have been used in dentistry in decades
      but very little is known about their behavior and biological impact as framework
      materials in implant dentistry. Furthermore, few studies have evaluated and
      compared the clinical and radiological results of abutment and abutment-free
      implant treatment concepts. AIMS: To investigate in vitro CoCr and commercially
      pure (CP) titanium frameworks regarding precision of fit, estimated material
      degradation and possible adverse cellular responses. In addition, to
      retrospectively evaluate the clinical and radiological five-year outcome of
      abutment-free porcelain-veneered CoCr prostheses compared to acrylic-veneered CP
      titanium prostheses, with or without abutments. MATERIALS AND METHODS: Paper I.
      Two groups of cast, sectioned and laser-welded frameworks were fabricated, either
      in a CoCr alloy or in CP titanium. A third group comprised computer numeric
      controlled (CNC) milled CP titanium frameworks. Measurements of fit were
      performed with a coordinate measuring machine. Paper IL Ion leakage from titanium
      implants, CoCr and CP titanium framework sections into artificial saliva was
      observed with mass spectrometry. Surface structures were registered with optical
      interferometry. Paper III. Viability of epithelial cells and fibroblasts cultured
      on CoCr and titanium specimens were evaluated with the Alamar Blue method.
      Specimen surface structures were registered with optical interferometry and cell
      morphology observed with SEM. Paper IV A test group (n = 40) comprised of
      patients treated with prostheses made at implant level in dental-porcelain
      veneered CoCr alloy (n = 15) or acrylic-veneered CP titanium (n = 25). A control
      group (n = 40) was provided with prostheses made at abutment level, in acrylic
      veneered CNC-milled CP titanium. Clinical and radiological data were evaluated
      after five years. RESULTS: Paper I. The transversal width decreased in CoCr
      frameworks, but increased in both groups of titanium frameworks. Less vertical
      distortions were present in the CNC-milled frameworks compared to the two other
      groups. Paper II. Significantly more cobalt ion leaked than titanium and chrome
      ions. Both framework sections and implants roughened after saliva exposure. Paper
      III. Both cell groups were more viable on titanium than on CoCr surfaces. The
      CoCr surfaces had a lower height deviation but were denser than the CP titanium
      surfaces. No major deviations from normal cell morphology were present. Paper IV.
      No significant differences in implant cumulative survival rates were demonstrated
      between the test and control groups after five years in function (98.6% and 97.6
      %, respectively). No major differences in bone levels were demonstrated.
      Mucositis and veneer fracture were the most common complications in all groups.
      CONCLUSIONS: None of the frameworks presented a perfect, completely "passive
      fit". There were indications of active corrosive processes for both implants and
      framework materials. Epithelial cells and fibroblasts preferred titanium to CoCr
      surfaces. The clinical outcomes of implant level prostheses made of porcelain
      veneered CoCr or acrylic-veneered titanium seem comparable to acrylic-veneered
      titanium prostheses made at abutment level.

PMID- 20143575
TI  - [The parameters of genetic variability and of selection in offsprings of exposed
      humans].
AB  - Mayak workers offsprings parameters of genetic variability including
      heterozygosity, genetic combinations, quantitative characteristics of genetic
      class reproduction, genetic identity and intervals, and parameters of selection
      including relative adaptation of genetic classes and mean adaptation depending on
      preconceptive doses of parents' exposure were studied. Genetic markers of Mayak
      workers, their children and grandchildren were defined. Children whose parents
      had preconceptive doses of more than 200 cGy in comparison with the control group
      had the heterozygosity reduction by Hp system and tendency to the mean
      heterozygosity reduction studied genetic system. Also they had modifications in
      the frequency of combinations of separate genotypes and blood groups, genetic
      identity reduction and genetic interval increasing, increasing of the mean
      adaptation and reduction of the mean coefficient of selection by genetic system
      of Hp. Consequently the children of workers, preconceptively exposed to gamma
      radiation in doses over 200 cGy, are susceptive to the gametic selection on
      system of Hp that realizes at their conception. In grandchildren, whose
      grandparents had preconceptive doses over 200 cGy, no changes in genotype Hp
      distribution were detected compared to controls. The absence of changes in
      genotype Hp distribution in workers' grandchildren is accounted for the absence
      of increased preconceptive exposure doses of their parents (F1-children), as well
      as for their marriages to the individuals (in 94.3% of cases), whose parents
      didn't have high (over 200 cGy) preconceptive exposure doses.

PMID- 20143576
TI  - [The dynamics of P-mobile Drosophila melanogaster element activation in
      controlled terms of protracted irradiation].
AB  - Verification of hypothesis about mobile element activation radiosensitivity
      change in the conditions of the prolonged irradiation was the research goal. The
      estimation of orientation of these changes depending on the accumulated dose and
      their characteristic times were conducted. Two Drosophila melanogaster strains
      (Canton-S and P-lines) for 20 generations were in the controlled terms of chronic
      irradiation with 3-dose rate (1.2 x 10(-8), 0.6 x 10(-8) and 0.12 x 10(-8) Gy/c).
      The dynamics of hybrid dysgenese frequency was explored for each generation of F1
      descendants from Canton-S and P-lines crossing. The gradual change of dose
      response of hybrid disgenesis depending on duration of irradiation of ancestors
      and dose rate was shown. The complex dynamics of hybrid dysgenese frequency
      depending on irradiation duration of ancestors and dose rate was shown. The
      cumulative effect of the prolonged irradiation shows up as adaptation at the
      lowest dose rate and as exhaustion at the highest dose rate. Question comes into
      discussion about the features of transitional process and including of protective
      and adaptive reactions hierarchy at the conditions of radiation factor chronic
      action.

PMID- 20143577
TI  - [Genetic changes in yeast cells Saccharomyces irradiated by fast neutrons with
      different dose rate].
AB  - No neutron dose rate effects in the wide range of 10(-3) Gy/s to 10(6) Gy/s were
      observed in yeast diploid cells for induction of mitotic segregation and crossing
      over. The RBE values for these effects were determined as doses ratio
      (Dgamma/D(n)) at maximum effects. The RBE were 2.2-1.9 for neutrons of the
      reactor BR-10 (E = = 0.85 MeV) and the pulse reactor BARS-6 (E = 1.44 MeV). The
      RBE values for genetic effects were 1.0 at the equal survival level for neutrons
      and gamma-rays 60Co.

PMID- 20143578
TI  - [Adaptive response comparison of CBA mice splenocyte and Drosophila melanogaster
      larva neuroblast, developed in conditions of chronic gamma-irradiation influence
      with low-dose rate].
AB  - The level of DNA damage and apoptosis of mice splenocytes, developed in condition
      of chronic gamma-irradiation with low-doze rate (8 +/- 2 cGy), in response to
      high-dose irradiation (2 Gy) in the completion of irradiation, as well in 30
      minutes after irradiation was analysed. Reaction of neuroblasts of Drosophila
      melanogaster larvae (4 cGy - priming dose, 3 and 6 Gy--challenging doses) is also
      investigated. The adaptive response by the level of DNA-damage is shown for both
      objects. This resistance is presumably connected to increase of DNA-damage repair
      efficiency in preirradiated objects, as well promotion of sensitivity to
      apoptosis (in the case of Drosophila larvae neuroblast). It is assumed, that
      observed changes may be result of selection of cell during development in
      condition of an chronic irradiation.

PMID- 20143579
TI  - [Different trend for changing of mammalian plasma (serum) antioxidant activity
      after irradiation at large and low-doses].
AB  - One of the path for research of antioxidant status in vivo is the determination
      of blood plasma (serum) antioxidant activity (AOA). AOA is an integral parameter
      for the contribution of different antiradical defense components which particular
      nomenclature is determined by a used method of definition. In the present work
      AOA is studied with usage of a system of suppression in vitro by blood plasma
      (serum) of a Fe(2+)-induced oxidation of a substrate from egg yolk lipoproteins.
      The contribution of separate components of a blood plasma to an integral index of
      AOA for human blood serum is studied. Urine acid, albumin, reduced glutathione,
      ascorbat, heparin, peroxidase and catalase had no activity. Apo-beta-lipoprotein,
      vitamin E, ceruloplasmin and transferring are introduce, possibly, the main
      contribution to AOA. The significant decrease of AOA was revealed after acute
      irradiation by gamma-rays of dogs (4.05 Gy) and mice (6 Gy). The irradiation of
      mice at low-dose (0.2 Gy), vice-versa, result to stimulation of AOA with clear
      peak value on 5 day. The possible reasons of quality difference for effects of
      large and low dose radiation with reference to antioxidant system of organism are
      discussed.

PMID- 20143580
TI  - [Dynamics of the functional status of autonomic nervous system in rats under
      combined radiation/thermal injury in case of an open burn wound and wound covered
      by the polymer film].
AB  - The peculiarities of the functional status of autonomic nervous system and
      physical efficiency were studied in white inbred rats under dynamics of combined
      radiation/thermal injury (CR/TI). The CR/TI model was obtained under total X-ray
      irradiation at dose level of 4.37 Gy and inflicting III degree burn injury making
      12% of body surface in 24 rats. The studies were performed under conditions of
      both spontaneous CR/TI development and protecting the burn wound against
      infection. In 12 rats the wounds were covered by polymer films treated with
      iodine and succinic acid. On days 3, 7, 14, 21 and 28 of CR/TI, as well as prior
      to CR/TI (datum level), heart rate variability (HRV) indices, the level of
      physical efficiency (the retention time of own weight on the vertical pole),
      indices of body mass, survival, and average life-soan of animals were recorded.
      For registration of ECG in awake rats, corrections of motor artifacts and
      analysis of HRV the original software program was used. R-R intervalograms were
      analyzed in time and frequency domains. The sliding window technique was used
      (100 R-R intervals with the step of 10 seconds; epoch of analysis--7 minutes).
      The obtained data indicated that the survival level and the average life-span in
      rats with the film-covered burn wound were higher as compared to the "pure"
      CR/TI. At the same time body mass and physical efficiency in animals of both
      groups did not differ in practice. Data on the functional status of autonomic
      nervous system were more informative. In rats with film-covered burn wound the
      dynamics of HRV indices had a biphasic character with the tending to
      normalization beginning from day 7 of CR/TI, whereas in case of an open wound HRV
      indices were characterized by monotonous growth until the end of observations. In
      the overall picture of the CR/TI in both groups of animals the sympathotropic
      effects of burn stress prevailed. Methods of mathematical analysis of HRV under
      conditions of CR/TI were for the first time used in this study. The research
      outcomes signify to the expediency to apply these methods for obtaining data on
      functional state of the autonomic nervous system in CR/TI models in small
      laboratory animals.

PMID- 20143581
TI  - [The influence of multipotent mesenchymal stromal cells of bone marrow on process
      of local radiation injury in rats after local beta-irradiation].
AB  - The influence of multipotent mesenchymal stromal cells (MMSC), got from allogenic
      bone marrow, on local radiation injury in rats after beta-irradiation by a source
      90Sr/90Y in a dose 140 Gy under various conditions and ways transplantation was
      studied. It was established, that transplantation MMSC, allocated on
      biodegradative membranes, which have been carried out for 21 day after an
      irradiation in conditions minor surgical of ulcers, resulted in reduction of the
      area of local beam defeats and acceleration of healing of skin, in comparison
      with the control of an irradiation. The introduction of suspension MMSC
      subcutaneous around of the center of a defeat at 8 day after an irradiation
      caused earlier healing of ulcers. It was concluded, that application of MMSC is
      perspective for treatment of local radiation injury and necessity of development
      of optimum conditions of their use at cell therapy of radiation injury of skin.

PMID- 20143582
TI  - [Congenital malformations among offspring of the liquidators of the consequences
      from Chernobyl accident].
AB  - The frequency and the structure of congenital malformations at children of the
      liquidators of the consequences from Chernobyl accident, undergone to an external
      scale gamma-irradiation in dozes up to 25 cGy. In total is surveyed 2379 newborn
      at which is revealed 318 intrauterine development defects. The received results
      are compared to the earlier published data on birth of congenital malformations
      in families of the fathers who have undergone to an irradiation in connection
      with professional activity at the enterprises of a nuclear industry, with
      emergency irradiation, with irradiation as a result of explosions of nuclear
      bombs in Japan, and are discussed from positions of the basic rules (situations)
      of radiating genetics. Total frequency, the frequency of forms 21 of inherent
      defects of development, taken into account in the International register of
      congenital malformations and frequency 9 forms heaviest of congenital
      intrauterine development defects with the high contribution mutation components
      at children of the liquidators authentically is higher than on the average on
      Russian Federation. The dependence of the frequency congenital malformations at
      children from dozes of an irradiation of the fathers--liquidators is revealed.
      The curve of dependence of the frequency of congenital malformations from time,
      past after work up to copulation carries arched character with peak of rise of
      frequency of congenital malformations in 2-3 years and decrease in 6-7 years.

PMID- 20143583
TI  - [Radioecological studies of freshwater mollusks in the Chernobyl accident
      exclusion zone].
AB  - Species-specificity and dynamics of 90Sr, 137Cs and some transuranic elements
      accumulation in bivalve and gastropod freshwater molluscs of the Chernobyl
      exclusion zone during 1997-2008 was analyzed. The results of radiation dose and
      chromosome aberration rate estimation and the analysis of hemolymph composition
      of freshwater snail (Lymnaea stagnalis L.) was produced. The absorbed dose rate
      was registered in the range of 0.3-85.0 microGy/h. In closed water bodies the
      heightened chromosome aberration rate (up to 27%) in embryo tissues, and also the
      change of haematological indexes for the adult individuals of snails was
      registered.

PMID- 20143584
TI  - [Radioecological situation in the Iset riverside settlements].
AB  - This paper presents the results of radioecological study of the Iset River and
      riverside settlements in 1961-2002. In 1961, specific activity of 90Sr in the
      Iset River water below the Techa River mouth was 44.4 Bq/l and decreased to 3.2
      Bq/l in 2002. Annual Techa River run-offinto the Iset River was, on average, 2 x
      10(12) Bq of 90Sr in 2000-2004. Density 90Sr-contamination of floodplain soils
      decreased downstream the Iset River from 146.1 to 37.1 kBq/m2 near the Iset River
      mouth. In 1977, 90Sr-specific activity of fish muscles was 18 Bq/kg and decreased
      to 2 Bq/kg in 2002. An average 90Sr-specific activity in milk in settlements
      located at distances of 12-26 km from the Techa River mouth was 10.2 Bq/l in 1961
      and 1.2 Bq/l in 2001. The rate of 90Sr transfer in chain "floodplain soils -->
      milk" was 2 x 10(-5) (Bq/l)/(Bq/m2). Annual dietary 90Sr-intake by adult
      residents of the Iset riverside settlements did not exceed an annual limit of
      intake in 1964-2002.

PMID- 20143585
TI  - [The dynamics of 137Cs and 40K accumulation in the tissue of food species of fish
      in the Tobol and Irtysh Rivers during 1995-2007].
AB  - The results of long-term investigations of 137Cs and 40K accumulation in the
      tissue of food species of fish in the Tobol and Rivers were analyzed. It was
      revealed, that the highest specific activity of 137Cs is characteristic for
      predatory species of fish. Yearly, seasonal and age peculiarities of 137Cs
      accumulation in fish were examined in this work. The tendency to the lowering of
      the specific activity of the man-caused 137Cs values was revealed for the entire
      time of radio-ecological investigations of fish from the Tobol and Irtysh Rivers.
      The comparative analyses of the 137Cs accumulation in fish tissue were carried
      out at the different parts of the studied rivers.

PMID- 20143586
TI  - [The distribution of artificial radionuclides in the biomass of macrophytes of
      the Yenisei River].
AB  - The Yenisei River is contaminated with artificial radionuclides due to the
      operation of the Mining-and-Chemical Combine (MCC), Rosatom, producing weapon
      grade plutonium for several decades. Artificial radionuclides including
      activation isotopes and transuranics, are detected in the biomass of submerged
      aquatic plants of the river. We investigated the distribution of artificial
      radionuclides in the biomass of macrophytes from radioactively contaminated part
      of the Yenisei River with chemical fractionation techniques. Artificial
      radionuclides were detected in extracellular and intracellular compartments of
      the macrophytes. The distribution of radionuclides among the biomass fractions
      differed essentially. 54Mn was preferably in mobile, exchangeable form compared
      to other isotopes. Essential portion of 137Cs was in non exchangeable form.
      Significant activity of artificial radionuclides was detected in the particles of
      suspended matter of the river, attached to the plant surfaces. Radioactive
      isotopes were distributed among biomass fractions similar to stable isotopes. The
      distribution of potassium and 137Cs differed essentially. On the basis of the
      results obtained the assumptions on the further migration of radionuclides
      accumulated by aquatic macrophytes in the Yenisei River have been done.

PMID- 20143587
TI  - Venous clinic and arteriovenous malformation center at the Methodist Debakey
      Heart & Vascular Center.

PMID- 20143588
TI  - Overview of venous disease.

PMID- 20143589
TI  - Venous imaging.

PMID- 20143590
TI  - Endoluminal treatment of varicose veins.

PMID- 20143591
TI  - Laser therapy for the treatment of telangiectasias and reticular veins in the
      lower extremity.

PMID- 20143592
TI  - Deep venous thrombosis: prevention and treatment.

PMID- 20143593
TI  - Central venous stenosis--endovascular and surgical treatments.
AB  - Central venous stenosis remains a difficult disease to diagnose and treat. The
      etiology of the lesion and the condition of the patient dictates the treatment
      strategy. Both endovascular and surgical approaches are successful and are best
      accomplished by the endovascular cardiovascular surgeon.

PMID- 20143594
TI  - Endovascular therapy for pelvic congestion syndrome.

PMID- 20143595
TI  - Robot saves patient's transplanted lung.

PMID- 20143596
TI  - Arteriovenous malformations--diagnosis and treatment.

PMID- 20143597
TI  - Reducing obesity: policy strategies from the tobacco wars.

PMID- 20143598
TI  - [Regional distribution of physicians in Croatia].
AB  - The aim of this study was to show regional distribution of physicians in Croatia.
      Number of physicians members of the Croatian medical chamber and number of
      physicians in the system of mandatory health insurance were compared between the
      counties. In 2006 in Croatia there were 276 physicians per 100,000 inhabitants,
      i.e., 215 physicians per 100,000 inhabitants in the system of mandatory health
      insurance. The fewer number of physicians per 100,000 inhabitants in the system
      of mandatory health insurance, less then 150, were in Koprivnica-Krizevci County,
      Lika-Senj County and Vukovar-Srijem County, while the greatest number of
      physicians, more than 250 per 100,000 inhabitants, were in the City of Zagreb and
      Zagreb County, and Primorje-Gorski kotar County. There were significant
      differences in the number of physicians per 100,000 inhabitants between the
      counties (chi2 = 148.7, DF = 19, P < 0.001, chi2-test). Number of general
      practitioners (GPs) per 100,000 inhabitants in Croatia were 54.2, with range from
      47.1 in Pozega-Slavonia County to 61.8 in Primorje-Gorski kotar County. Number of
      physician specialties in four basic specialties per 100,000 inhabitants in
      Croatian hospitals were for internal medicine 19.1, general surgery 11.0,
      gynecology and obstetrics 6.7 and pediatrics 7.8. There were significant
      differences in the number of physicians in four specialties (internal medicine,
      general surgery, gynecology and obstetrics and pediatrics) per 100,000
      inhabitants between the counties (chi2 = 76.0, DF = 19, P < 0.001, chi2-test).
      Apart from the insufficient number of physicians in Croatia, an inadequate
      allocation of physicians in certain counties is also evident.

PMID- 20143599
TI  - [Trauma of the brachial plexus and associated vascular injury--a case report].
AB  - Acute vascular trauma in the axillary region is usually associated with brachial
      plexus injury and presents a great challenge to surgeon and formidable obstacle
      to restore a useful limb function. Interdisciplinary operative and postoperative
      approach is mandatory providing an optimal care of these severe patients. Here we
      present a case of neurovascular trauma that affected axillary artery and vein,
      complete transection associated with complete transection of the brachial plexus.
      Immediately after admission emergency surgery was performed and in postoperative
      follow up, after several operations and rehabilitation that continued for 24
      months, entire functional recovery was achieved without any disabling
      consequences.

PMID- 20143600
TI  - [Kidney transplantation in a patient with urinary diversion].
AB  - Kidney transplantation is the most efficient treatment in patients with end-stage
      renal disease. Transplantation in patients with urinary diversion is an effective
      treatment for patients with chronic renal insufficiency and abnormal lower
      urinary tract. Graft and patient survival is comparable to that with classical
      ureterovesical anastomosis. We present one patient with urinary diversion (ileum
      conduit) who was successfully transplanted in our center two years ago.

PMID- 20143601
TI  - [Total knee arthroplasty in the cardiac transplant patient--a case report].
AB  - We present a 66 year-old diabetic patient who 4 years ago underwent cardiac
      transplantation and 1 year ago was implanted a total knee arthroplasty due to
      arthrosis. In the literature and reference books the arthroplasty in such
      patients is mainly related to aseptic necrosis of the joints as a result of
      taking immunosuppressive therapy (corticosteroids). Our patient didn't have an
      aseptic necrosis but a classical arthrosis of the knee. Although our patient
      didn't have so strong pain as patients with aseptic necrosis, we decided to do
      the knee arthroplasty. The procedure went properly and postoperative time,
      recovery and knee function were excellent. Implantation of endoprosthesis in a
      cardiac transplant patient shouldn't be retained only for cases of aseptic
      necrosis of a joint, which occurs due to immunosuppressive therapy, but also for
      the cases of classical arthrosis. Good preoperative, perioperative and
      postoperative care and good surgery technic make this procedure safe in cardiac
      transplant patients as in nontransplanted patients. To the best of our knowledge
      this is the first case of implantation of knee endoprosthesis in a cardiac
      transplant patient in Croatia.

PMID- 20143602
TI  - [Peripheral blood hematopoietic stem cell collection].
AB  - Summary. Peripheral blood hematopoietic stem cells (PBSC) have numerous advatages
      in comparison with traditionally used bone marrow. PBSC collection by
      leukapheresis procedure is simpler and better tolerated than bone marrow harvest.
      PBCS are mobilized by myelosupressive chemotherapy or/and hematopoietic growth
      factors. Leukapheresis product contains PBSC along with lineage commited
      progenitors and precursors which contribute to faster hematopoietic recovery. In
      "poor mobilizers" options are large-volume leukapheresis (LVL) procedure or
      second generation of mobilising agents (pegfilgrastim, CXCR4 receptor
      antagonists). Total blood volume is processed 2-3 times in standard procedure
      compared to more than 3 times in LVL. LVL yields significantly higher numbers of
      CD34+ cells. Adverse effects of leukapheresis are electrolyte disbalance
      (hypocalcemia) caused by citrat administration and risk of bleeding due to
      trobocytopenia and heparin administration. PBSC collection and product quality
      control are regulated by national and international standards and
      recommendations.

PMID- 20143603
TI  - [Side effects of radiotherapy in oral cavity: diagnosis, prevention and treatment
      guidelines].
AB  - To avoid, or at least to reduce complications in patients who require head and
      neck radiotherapy, adequate oral cavity treatment is necessary before the
      therapy. Recent management guidelines speak of possibilities of preventing
      osteoradionecrosis with hyperbaric oxygen, using long-wave ultrasound in
      stimulating osteoblasts growth, and surgical transfer of submandibular salivary
      glands to submental area with 99% effectiveness in preventing xerostomia, besides
      traditional therapy. Preventive measures are naturally the best choice, since
      late complications treatment is not needed as often, and should draw special
      attention of physicians and patients. Since wide a spectrum of preventive and
      curative measures is required, the need exists for standard teams to look after
      the patients during and after radiotherapy, and which should include, besides
      radiotherapist, oral or maxillofacial surgeon in cooperation with oral medicine
      specialist.

PMID- 20143604
TI  - [Croatian Thyroid Society guidelines for rational detection of thyroid
      dysfunction].
AB  - Thyroid dysfunction is common in the population, especially in women, and thyroid
      diagnostic tests are among the most often used diagnostic procedures nowadays.
      Many thyroid societies developed guidelines for the detection of thyroid
      dysfunction. An interdisciplinary team of experts from the Croatian Thyroid
      Society studied guidelines of other thyroid societies and international
      publications, and according to our tradition and clinical practice developed
      guidelines for rational detection of thyroid dysfunction; hypothyroidism and
      hyperthyroidism. The aim of these guidelines is to recommend evidence-based and
      rational approach to the detection of thyroid dysfunction.

PMID- 20143605
TI  - [First open heart surgery in hypothermia in Croatia performed in 1957].
AB  - In Zagreb, at the Surgical Department of University Hospital "Dr Ozren Novosel",
      today "Merkur" the first operation in hypothermia was performed on October 25th,
      1957, on the patient with pulmonary valve stenosis. It allowed total circulatory
      interruption to do the operation in the open heart successfully, and this was the
      first such operation not only in Croatia but in the broader context of former
      Yugoslavia.

PMID- 20143606
TI  - [On (internal) propedeutics].

PMID- 20143607
TI  - [Clinical and cytogenetic factors of prognosis in glial tumors of the brain].
AB  - BACKGROUND: The purpose of this study is to assess clinical, morphofunctional and
      molecular factors of prognosis in patients with malignant cerebral gliomas.
      MATERIALS AND METHODS: Retrospective analysis of follow-up of surgical and
      complex treatment of 95 patients with cerebral gliomas was performed. The series
      included 81 primary case and 14 recurrent cases. In all patients age, sex,
      clinical, topographic, morphological and therapeutic factors were analyzed. In 47
      patients molecular and genetic prognostic factors including p51, MGMT, p16, PTEN
      and hyperproduction of miRNA21 in tumor cells were investigated. RESULTS AND
      CONCLUSIONS: We established significant prognostic factors for cerebral gliomas.
      They include: histological nature, age, sex, comorbidity. Complex treatment of
      glial tumors (surgical resection + radiation therapy) correlated with longer life
      expectancy in comparison with patients who received only surgical treatment.
      Patients wish mutations in tumor cells had longer survival period in comparison
      with mutation-free patients. This finding allows application of molecular and
      genetic tumor markers as independent prognostic factors in glial cerebral tumors.

PMID- 20143608
TI  - [Neurovascular interactions in hemifacial spasm].
AB  - The article describes our results of surgical treatment of 37 patients with
      hemifacial spasm (HS) as well as results of morphological studies of facial nerve
      root exit zone (REZ). Morphological studies demonstrated that extension of
      central myelinated zone differed between 0.9 and 3.6 mm (mean 2.24 mm). This zone
      did not exceed 1.1 diameter of facial nerve. Intraoperative findings included 27
      cases of compression by a single vessel and 9 cases of compression by multiple
      vessels. In cases of compression by a single vessel the offending artery was AICA
      in 11 cases, PICA in 12 cases and VA in 4 cases. In 35 patients complete
      decompression of facial nerve REZ was achieved. In one case complete
      decompression was not possible due to penetration o vestibular nerve by AICA
      which prevented safe manipulations of the artery and nerves. Excellent results of
      surgical treatment were achieved in 33 patients. In 1 described case the outcome
      was unsatisfactory. We observed no serious postoperative complications. Vascular
      decompression is highly effective and relatively safe procedure for treatment o
      HS. HS results from compression of central myelinated zone of facial nerve thus
      surgical decompression should be preformed close to REZ at the brainstem.

PMID- 20143609
TI  - [Neuropsychological signs in patients with arteriovenous malformations,
      cavernomas and hematomas of cerebellum].
AB  - Neuropsychological assessment was performed in 13 patients with arteriovenous
      malformations and 12 with cavernomas and hematomas of cerebellum before and after
      surgery. In all patients we identified syndromes that were similar to the damage
      of different areas of neocortex (predominately frontal lobe). Apraxia and
      disturbance of verbal memory were the most frequent signs. Half of patients after
      AVM embolization and all patients after direct surgery developed deterioration of
      verbal memory. Some patients after manipulations on right cerebellar hemisphere
      had micrography and perseverations. There were no severe mental disorders neither
      before nor after surgery. That was controversial to other similar studies. The
      most severe cognitive disorders were found after surgery on superior cerebellar
      artery and its branches.

PMID- 20143610
TI  - [Clinical studies of transpedicular system using TiNi rod with functionally
      optimal rigidity].
AB  - Transpedicular metal systems are very widely applied in surgical treatment of
      spinal pathology. Recently TiNi constructions were introduced into practice. This
      material is characterized by shape memory, superior elasticity and cyclic
      durability. Adequacy of mechanical interactions of tissues and TiNi-based alloys
      allows to suggest that TiNi systems are more physiological and functional in
      comparison with steel and titanium alloys. This enabled development of
      transpedicular TiNi system with good safety and stability properties in
      combination with physiologic compatibility and high functional value of TiNi
      connections. We performed computer modeling of different spine lesions treated by
      transpedicular systems using ANSYS program kit. Statistic and cyclic tests of
      transpedicular systems were made using test machine 'Terotest' according to
      international standards. Results of studies allowed to formulate guidelines for
      application of transpedicular systems with different level of rigidity in
      treatment of injuries and degenerative lesions of the spine. The authors
      performed 53 operations in patients with lesions of lower-thoracic and lumbar
      spine using TiNi rod with functionally optimal rigidity and obtined good
      postoperative results.

PMID- 20143611
TI  - [Surgical treatment of benign dumbbell-shaped intra-extravertebral tumors].
AB  - BACKGROUND: Aims of the research at was to determine optimal surgical strategy or
      treatment of dumbbell-shaped tumors. MATERIALS AND METHODS: We present a series
      of 48 dumbbell-shaped tumors consecutively observed at the spine surgery
      department of the Burdenko Neurosurgical Institute (Moscow, Russia) during a
      period from 1991 to 2005. Mean age of patients was 41.4 years. Mean duration of
      symptoms was 8.2 years. In 24 cases (50%) tumors were located in cervical region,
      in 15 (31.2%) in thoracic region and in 9 (18.7%) in lumbosacral region. RESULTS
      AND CONCLUSIONS: The results of our study showed that total one-stage tumor
      removal is optimal. Selection of approach is based on tumor location. In cervical
      level depending on placement of tumors we used posterior approach, posterior
      lateral approach, and "far lateral" approach. In thoracic and lumbosacral level
      we applied lateral extracavitary approach. One-stage surgery of dumbbell-shaped
      neuromas and neurofibromas provides excellent prognosis after gross total
      removal.

PMID- 20143612
TI  - [Arteriovenous malformation of septum pellucidum in combination with persistent
      trigeminal neuralgia].
AB  - A 16-year-old boy with arteriovenous malformation (AVM) of septum pellucidum in
      combination with left side persistent trigeminal artery (PTA) is described.
      Presentation of AVM included severe intracranial hemorrhage and the lesion was
      removed surgically. The case deserves interest for two reasons. 1) The
      observation demonstrates the possibility of increased pressure in the afferent
      arteries of AVM. It was illustrated by distinctive displacement of the zones of
      the hemodynamical balance around the circle of Willis. The raised pressure in
      conditions of shunting can be explained using principles of the constant shear
      stress in the vascular system. 2) The observation of the features of venous
      system that may be causative for PTA. These features included presence of the
      large anastomotic vein between petrosal and cavernous sinuses, enlargement of
      petrosal sinuses and shrinking of transverse sinus ipsilateral to PTA.

PMID- 20143613
TI  - [Rare observation of giant pituitary adenoma spreading into posterior cranial
      fossa].
AB  - A case observation of unusual course of pituitary adenoma is presented. In 47
      year old male patient with endo-supra-laterosellar pituitary adenoma and active
      acromegaly 2 different tumors were discovered intraoperatively during surgery for
      recurrence of the primary tumor. The first tumor was pituitary adenoma with
      nuclear polymorphism and the second was meningotheliomatous meningioma with
      solitary mitoses. After surgery the patient received radiation therapy. After 5
      years the patient developed visual deterioration and clinical signs of tumor of
      left cerebellopontine angle. After removal of posterior fossa lesion, pituitary
      adenoma was verified.

PMID- 20143614
TI  - [Vein of Galen malformations in children].
AB  - The literature review deals with historical stages of understanding of vein of
      Galen AVM pathogenesis in children up to state-of-art considerations. The authors
      analyzed existing classifications, clinical presentation, variants of natural
      course, problems of diagnostics and management of these patients. Causes of
      complications and possible ways for their prevention are also discussed.

PMID- 20143615
TI  - [About investigations of socioeconomic consequences of neurotrauma].

PMID- 20143616
TI  - The purpose of life.

PMID- 20143617
TI  - A focus on clinical gait analysis.

PMID- 20143618
TI  - The need to stand.

PMID- 20143619
TI  - The importance of strengthening.

PMID- 20143620
TI  - The core of rehab in 3-D.

PMID- 20143621
TI  - Liability insurance for therapy practitioners: are your bases covered?

PMID- 20143622
TI  - Capital expenditures gear up to usher in a new decade.

PMID- 20143623
TI  - 2010 OIG Work Plan. Implications for rehab, skilled nursing, and psychiatric
      providers.

PMID- 20143624
TI  - [Loosening of condensed chromatin in human blood lymphocytes exposed to
      irradiation with a low-energy He-Ne laser].
AB  - It was shown that, 1 h after irradiation of human blood lymphocytes with a He-Ne
      laser at 56 J/m2 (5.6 W/m2, 10 s), the relative optical density of condensed
      chromatin masses observed in ultrathin sections was decreased (p < 0.01); i.e.,
      the condensed chromatin became less compact. Such transition of condensed
      chromatin to a more "open" state may improve its availability for regulatory
      proteins and transcriptional factors. The irradiation also results in dispersion
      of condensed chromatin clumps in the nucleoplasm and enhancement of their
      angularity, i.e., in extension of the clump surface. These shifts, correlating
      with the activation of transcription, may be due to decompaction of the chromatin
      fibers not only on the periphery of chromatin clusters in the center of the
      nucleus, but also within the masses of condensed chromatin.

PMID- 20143625
TI  - [Oxidative modification of proteins and antioxidative blood activity of ground
      squirrels during induced awakening from winter sleep].
AB  - The intensity of oxidative modification of plasma proteins and activity of the
      antioxidative system of the blood of the ground squirrels during awakening from
      winter sleep is studied. During waking of animals, processes of oxidative
      modification of proteins in the blood plasma intensify. While the body
      temperature rises, the antioxidative activity of hydrophylic components of the
      blood plasma grows essentially, and erythrocyte superoxide dismutase too.
      Activity of erythrocyte catalase at all stages of waking is definitely higher
      than in the control. The received results evidence that the high activity of
      various links of antioxidative blood protection provides stability to oxidative
      stress during waking of animals from deep sleep.

PMID- 20143626
TI  - [Biological activity of metabolites of the herb Kalanchoe diagremontania (Hamet
      de la Bbathie) Jacobs et Perr].
AB  - In this study we investigated the hemolytic, antimicrobial, and phytoregulatory
      activity of various classes of lipids (triacylglycerols, free fatty acids (FFA),
      the glyceroglycolipids monogalactosyl diacylglycerol (MGDG), sulfoquinovosyl
      diacylglycerol (SQDG)), sterols, all of them were obtained from the medical herb
      Kalanchoe diagremontiana, and also pigments, phenolic compounds (FC),
      polysaccharides, and ethanol extract (EE) of the herbal. It was established that
      EE, FC, FFA, and sterols display pH-dependent membranothropic activity. FFA
      showed antimicrobial activity and stimulated growth of buckwheat stalk sprouts.
      K. diagremontiana glyceroglycolopids did not display expressed biological
      activity. Caroteniods displayed pH-independent membranothopic action and
      antibacterial activity. Chlorophylls displayed antimicrobial action, but did not
      influence erythrocytes and buckwheat sprouts. Polysaccharides acted against the
      microorganisms Safale S-04, Candida albicans, Fusarium oxysperum and buckwheat
      sprouts.

PMID- 20143627
TI  - [Setaria viridis tolerance of high zinc concentrations].
AB  - The effect of high zinc concentrations on the growth and photosynthetic apparatus
      of Setaria viridis (L.) Beauv. was investigated under laboratory conditions and a
      vegetation experiment. The experiments showed that zinc concentrations of 10(-6)
      to 10(-3) M did not influence seed germination. Moreover, zinc in concentrations
      of 40 and 80 mg kg(-1) substrate had no significant effect on most of the plant
      growth parameters. However, higher metal concentrations (160 and 320 mg kg(-1)
      substrate) inhibited shoot biomass, leaf area, inflorescence length, and biomass.
      At the same time, parameters such as the content of chlorophyll (a + b), F0,
      F(v), and the F(v)/F(m) rate were not reduced even in the presence of zinc in the
      highest concentrations (320 mg kg(-1) substrate). S. viridis tolerance of high
      zinc concentrations, as well as its capacity to accumulate zinc in roots and
      shoots, suggests the plant can be used for phytoremediation of zinc polluted
      soils.

PMID- 20143628
TI  - [Ultrastructure and phylogeny of colpodellids (Colpodellida, Alveolata)].
AB  - The structure of cells of the predatory flagellates Colpodella pseudoedax and C.
      unguis was studied. The cell was found to contain two heterodynamic flagellae,
      three-membrane pellicle, micropores, subpellicular microtubulae, microtubular
      open conoid, roptries, micronemes, extrusive organelles (trichocysts), and
      mitochondria with tubular cristae. Upon discharging, trichocysts form cross
      striated bands. The thin-walled cylinder lies in the transitional zone of the
      flagellae. Cells reproduce by means of longitudinal binary fission. The
      similarities between given species and other colpodelids and such between
      perkinsea, sporozoans, and dinoflagellates are discussed.

PMID- 20143629
TI  - [Individual growth of Lymnaea stagnalis (Lymnaeidae, Gastropoda): II. Late
      postlarval ontogeny].
AB  - Our investigation on the growth of 14 individuals of the great pond snail Lymnaea
      stagnalis was performed in an aquatic culture at 18 degrees C beginning from the
      10th week after hatching until death. It has been demonstrated that the increase
      in the mollusk mass follows an S-like curve during the whole studied period.
      Linear growth (conch height) follows a parabolic (convex) curve until the age of
      39 weeks. Both weight and linear growth during studied period significantly
      approximate to the Bertalanffy equation, while the interrelation between mass and
      conch height corresponds to the allometric equation. The meanings of the
      coefficients of these equations do not differ significantly in different
      individuals. At the age of 38 to 39 weeks, all mollusks demonstrate breakage in
      the curve of linear growth, then followed with abrupt slowing of growth until
      stopping or even decreasing in size in some cases. Neither the Bertalanffy
      equation nor the allometric relation describe the linear growth of individuals
      with ages exceeding 39 weeks.

PMID- 20143630
TI  - [The effect of cocaine on kinetics of alpha1-adrenergic contractile response in
      different portions of the rat vas deferens].
AB  - The effect of cocaine (10 microM) on the kinetics of contractile response to
      noradrenaline (NA) was studied in the rat epididymal and prostatic vas deferens.
      Cocaine caused an acute increase in vas deferens adrenergic sensitivity primarily
      due to blockage of NA neuronal capture. The presynaptic action prevailed in the
      epididymal half: the EC50 value decreased 32-fold with a slight increase of the
      maximum adrenergic response more evident in the prostatic half. In the presence
      of cocaine, the prostatic contraction to NA was mediated not by a single pool of
      alpha1-adrenoceptors like in epididymal vas deferens but by two. Its high
      affinity pool had the same affinity as alpha1-adrenoceptors of the epididymal
      half, the affinity value of the low one was 36-fold less, and the total maximal
      response of both pools increased 4.5-fold. The differences in cocaine effect on
      the rat epididymal and prostatic vas deferens contractions to NA appear to be
      caused by the different sources of Ca2+ involved in these responses.

PMID- 20143631
TI  - [Spacial structure of epiphytic yeast communities on fruits of Sorbus aucuparia
      L].
AB  - The subject of this research is epiphytic yeast communities that form on the
      surface of Sorbus aucuparia. The object is to make quantitative assessment of the
      yeast communities' differentiation of the same but distant substratum. Results of
      the factor variance nidicolous analysis demonstrated that with increase in
      distances, there are increases in the variation of total number and relative
      abundance of the dominant yeast communities. The average similarity between
      groups of single fruits (Sorensen's Quotient of Similarity) regularly decreased
      with distance. The results demonstrate that the number and structure of separate
      yeast groups depend not only on ecological factors but also on proximity to other
      communities. Such aggregation in the distribution of the microorganisms' species
      caused by migration and colonial resettlement should be taken into account when
      analyzing their diversity in natural habitats.

PMID- 20143632
TI  - [Microbiological monitoring of disturbed ground ecosystems of Siberia].
AB  - Microbiological analysis of different elements of the forest ecosystem (soil,
      leaf-litter) in zones of active anthropogenic (technogenic) impact shows that
      microbial complexes serve as an instrument of condition diagnosis and monitoring
      of ground ecosystems. Fluctuations of the number of microorganisms, the scale of
      the ETGM number, coefficient of microbiological activity, and the reaction of
      introduced population of Bacillus subtilis to different doses of pollution may be
      considered as convenient characteristics.

PMID- 20143633
TI  - [Population dynamics of glochidia of the freshwater pearl mussel Margaritifera
      margaritifera L., parasitizing on juvenile Salmonidae fishes in northern water
      reservoirs].
AB  - This paper presents data on the population dynamics of glochidia of the
      freshwater pearl mussel Margaritifera margaritifera L. (1758) (a declining
      species of European fauna), parasitizing on juvenile Salmonidae fishes in rivers
      of northern Europe. It was found that the number of glochidia parasitizing on
      gills of juvenile salmon and trout in explored water reservoirs are stimulated by
      negative binomial distribution. Estimation of the distribution parameter allows
      us to obtain statistically valid data on the population number of pearl mussel
      and to judge the stable character of interactions in the host-parasite system
      (balance of host specimens that are resistant and nonresistant to infection).

PMID- 20143634
TI  - [Antidiabetogenic action of Pro-Gly-Arg and Pro-Gly-Pro-Arg peptides after their
      intranasal chronic administration to animals].
AB  - It was shown that chronic (over 7 days) intranasal injection of the Pro-Gly-Arg
      tripeptide to rats in the dose 1 mg/kg before the injection of a diabetogenic
      dose of alloxan, promotes effective defense against development of insulin
      dependent diabetes mellitus. At the same time, the tetra-peptide Pro-Gly-Pro-Arg
      did not show a hypoglycemic affect during diabetes mellitus provocation.
      Administration of Pro-Gly-Arg and Pro-Gly-Pro-Arg peptides also activates
      anticoagulation potential.

PMID- 20143635
TI  - [Distribution of strains of spore-forming bacteria of the genus Bacillus in the
      bottom sediments of Lake Khubsugul in Northern Mongolia as an indication of
      paleoclimate].
AB  - Data on the distribution and abundance of bacteria of the genus Bacillus in the
      bottom sediments of Lake Khubsugul have shown the predominance of strains that
      preferred low temperatures. This indicates fairly cold temperature conditions on
      the territory of the Khubsugul drainage area. On the whole, the dynamics of
      interchange of minimums and maximums of abundance of bacteria of the genus
      Bacillus is similar to the global climate fluctuations. Study of the enzymatic
      activity of pure cultures revealed that most strains studied possessed
      proteolytic activity; consequently, the dynamics of bacteria development is
      correlated with the supply of organic nitrogen-containing compositions.

PMID- 20143636
TI  - [Definition of the physiological condition of bacteria in soil by means of
      luminescent dye L7012].
AB  - By means of dye L7012, the number and physiological condition (damage rate of
      membranes) of bacterial cells is defined. The results testify to considerable
      physiological heterogeneity of bacteria cells in soils. In fresh samples of soil,
      the percentage of intact cells reached 60-70%. Damaged membranes occurred in 30
      40% of cells. The number of damaged cells dramatically increased downwards
      through the soil profile. Drying and freezing of soil samples considerably
      reduced the quantity of intact cells and increased the percentage of cells with
      damaged membranes; the number of intact cells was 10-20%. Treatment with biocide
      agents resulted in lysis of the majority of cells and cells injuries. However,
      some of the cells kept an intact cellular membrane, which testifies to the high
      stability of bacteria in soil. These data allow us to offer a method of staining
      a soil suspension with the use of luminescent dye L7012 with the quality of an
      express method that gives the chance to monitor the number and physiological
      condition of the bacterial complex of soils.

PMID- 20143637
TI  - [White-fronted and bean geese breeding near snowy owls, peregrine falcons, and
      rough-legged buzzards at the Taimyr Peninsula].
AB  - Studies were carried out in 2000-2007 near Medusa Bay (73.21' N, 80.32' E) and
      along the Agapa River (from 70 degrees 11', 86 degrees 15' E. down to the mouth
      71 degrees 26' N, 89 degrees 13' E), in the northwestern and central parts of the
      Taimyr Peninsula. White-fronted goose nests are usually spread in the tundra or
      placed in 1-3 nest colonies near nests or staging points of snowy owls, peregrine
      falcons, or rough-legged buzzards. The intent of white-fronted geese to breed
      near birds of prey or owls increases sharply when arctic fox numbers are high. In
      the area near Medusa Bay, white-fronted geese nest much closer to peregrine
      falcon nests than in the area along the Agapa River. At the latter location,
      white-fronted geese lose the competition to red-breasted geese, which are more
      numerous here. Bean geese, in spite of their greater size and ability to protect
      their nests against arctic foxes, really tend to breed near peregrine falcons or
      buzzards, where they manage to compete with red-breasted geese.

PMID- 20143638
TI  - [The first genetic evidence of hybridization between west European and northern
      white-breasted hedgehogs (Erinaceus europaeus and E. roumanicus) in Moscow
      Region].
AB  - The complex genetic examination of hedgehogs from the vicinity of the village of
      Nikolina Gora (Moscow region, Odintsovskii district) showed both Erinaceus
      europaeus and E. roumanicus in the sample. One of the hedgehogs was designated as
      E. roumanicus by the nucleotide sequence of 1 TTR intron but possessed
      mitochondrial DNA of E. europeus. Only one of the chromosomal pairs that differ
      in E. europeus and E. roumanicus was heteromorphic in this specimen. Its
      hybridous origin as the offspring of one or several back-crosses between F1
      hybrid and E. roumanicus was suggested.

PMID- 20143640
TI  - Current approaches to the diagnosis and treatment of systemic mastocytosis.
AB  - OBJECTIVE: To review the clinical manifestations of mastocytosis and examine the
      recommended diagnostic procedures and therapeutic options available for the
      treatment of this condition. DATA SOURCES: PubMed searches were performed for
      articles published regarding presentation and classification of mastocytosis and
      the diagnostic criteria and treatment options for this condition using the
      keywords mastocytosis, clinical features, World Health Organization diagnostic
      criteria, management, pathogenesis, and urticaria pigmentosa. Retrieved articles
      were surveyed for additional citations. STUDY SELECTION: Articles were reviewed
      for relevance to the study objectives, and more recent articles were
      preferentially included. Prospective studies were preferentially included when
      available. RESULTS: Mastocytosis is a heterogeneous disorder that results from
      clonal mast cell proliferation. Symptoms are typically limited to the skin in the
      pediatric population, requiring only symptomatic treatment with spontaneous
      resolution by puberty. Disease course in adults ranges from minimally symptomatic
      in most to highly aggressive but tends to be persistent. Symptoms can be protean
      and nonspecific. The mainstay of treatment consists of avoidance of triggers of
      mast cell degranulation and symptom-based therapy. CONCLUSIONS: Mastocytosis
      should be suspected in patients who present with a constellation of symptoms,
      including flushing, abdominal pain, diarrhea, unexplained syncope, and classic
      urticaria pigmentosa lesions. Diagnosis should be established by a bone marrow
      biopsy in all adults. Staging should be performed to assess disease burden and
      evidence of end-stage organ damage. Patients should be offered symptom-based
      treatment and cytoreductive therapy only for aggressive systemic mastocytosis or
      an associated hematologic malignant neoplasm.

PMID- 20143641
TI  - Evaluating approved medications to treat allergic rhinitis in the United States:
      an evidence-based review of efficacy for nasal symptoms by class.
AB  - OBJECTIVE: To evaluate how well the medications currently approved in the United
      States for allergic rhinitis (AR) treat nasal symptoms when examined according to
      Food and Drug Administration-indicated uses and dosages. DATA SOURCES: MEDLINE
      (1966 onward), EMBASE (1974 onward), and the Cochrane Library (2007) were
      systematically searched according to the following criteria defined at a
      roundtable meeting of the authors: randomized controlled trial, at least a 2-week
      duration, and approved indication and dosage in the United States. STUDY
      SELECTION: Data from studies that met the inclusion criteria were extracted into
      evidence tables, which were reviewed twice by the full panel of authors.
      Individual panel members also were asked to comment on abstracts, articles, and
      summary tables based on their known expertise. The entire faculty approved the
      selection of studies included in this review. RESULTS: Fifty-four randomized,
      placebo-controlled studies involving more than 14,000 adults and 1,580 children
      with AR met the criteria for review: 38 studies of seasonal allergic rhinitis
      (SAR; n = 11,980 adults and 946 children) and 12 studies of perennial allergic
      rhinitis (PAR; n = 3,800 adults and 366 children). The median percentage changes
      from baseline for total nasal symptom score for SAR were as follows: nasal
      antihistamines, -22.2%; oral antihistamines, -23.5%; intranasal steroids (INSs), 
      40.7%; and placebo, -15.0%. For PAR, the changes were as follows: oral
      antihistamines, -51.4%; INSs, -37.3%; and placebo, -24.8%. Data for mediator
      antagonists were limited. CONCLUSIONS: The data, although limited, confirm that
      INSs produce the greatest improvements in nasal symptoms in patients with SAR. In
      addition, INSs are effective for PAR, but the data were of variable quality, and
      oral antihistamines may be equally effective for some patients. The reporting of
      published data should be standardized to permit better comparisons in future
      studies.

PMID- 20143642
TI  - Patterns of inhaled corticosteroid use and asthma control in the Childhood Asthma
      Management Program Continuation Study.
AB  - BACKGROUND: Daily controller medication use is recommended for children with
      persistent asthma to achieve asthma control. OBJECTIVE: To examine patterns of
      inhaled corticosteroid (ICS) use and asthma control in an observational study of
      children and adolescents with mild-to-moderate asthma (the Childhood Asthma
      Management Program Continuation Study). METHODS: We assessed patterns of ICS use
      during a 12-month period (consistent, intermittent, and none) and asthma control
      (well controlled vs poorly controlled). Multivariate logistic regression examined
      the association between pattern of ICS use and asthma control. RESULTS: Of 914
      patients enrolled, 425 were recommended to continue receiving ICS therapy in the
      Childhood Asthma Management Program Continuation Study. Of these patients, 46%
      reported consistent ICS use and 20% reported no ICS use during year 1. By year 4,
      consistent ICS use decreased to 20%, whereas no ICS use increased to 57%; poorly
      controlled asthma was reported in 18% of encounters. In multivariate models
      controlling for age, sex, forced expiratory volume in 1 second, and asthma
      severity assessment, patients reporting consistent ICS use during a 12-month
      period were more likely to report poor asthma control (odds ratio, 1.6; 95%
      confidence interval, 1.2-2.1) compared with those reporting no ICS use.
      CONCLUSIONS: In this observational study of children and adolescents with mild-to
      moderate asthma, most did not report continued use of ICS. Patients recommended
      to continue receiving ICS therapy and reporting consistent ICS use were less
      likely to report well-controlled asthma even after controlling for markers of
      asthma severity. Although residual confounding by severity cannot be ruled out,
      many children and adolescents may not achieve well-controlled asthma despite
      consistent use of ICS.

PMID- 20143643
TI  - Relationships of methacholine and adenosine monophosphate responsiveness with
      serum vascular endothelial growth factor in children with asthma.
AB  - BACKGROUND: Airway hyperresponsiveness, which is a characteristic feature of
      asthma, is usually measured by means of bronchial challenge with direct or
      indirect stimuli. Vascular endothelial growth factor (VEGF) increases vascular
      permeability and angiogenesis, leads to mucosal edema, narrows the airway
      diameter, and reduces airway flow. OBJECTIVE: To examine the relationships
      between serum VEGF level and airway responsiveness to methacholine and adenosine
      monophosphate (AMP) in children with asthma. METHODS: Peripheral blood eosinophil
      counts, serum eosinophil cationic protein (ECP) concentrations, and serum VEGF
      concentrations were measured in 31 asthmatic children and 26 control subjects.
      Methacholine and AMP bronchial challenges were performed on children with asthma.
      RESULTS: Children with asthma had a significantly higher mean (SD) level of VEGF
      than controls (361.2 [212.0] vs 102.7 [50.0] pg/mL; P < .001). Blood eosinophil
      counts and serum ECP levels significantly correlated inversely with AMP
      provocation concentration that caused a decrease in forced expiratory volume in 1
      second of 20% (PC20) (r = -0.474, P =.01; r = -0.442, P =.03, respectively), but
      not with methacholine PC20 (r = -0.228, P = .26; r = -0.338, P =.10,
      respectively). Serum VEGF levels significantly correlated with airway
      responsiveness to AMP (r = -0.462; P = .009) but not to methacholine (r = -0.243;
      P = .19). CONCLUSIONS: Serum VEGF levels were increased in children with asthma
      and were related to airway responsiveness to AMP but not to methacholine.
      Increased VEGF levels in asthmatic children may result in increased airway
      responsiveness by mechanisms related to airway inflammation or increased
      permeability of airway vasculature.

PMID- 20143644
TI  - Correlation of plasma complement split product levels with allergic respiratory
      disease activity and relation to allergen immunotherapy.
AB  - BACKGROUND: Allergens, including dust mite and grass pollen, and mast cell
      tryptase are known to generate the complement split products (CSPs) C5a and C3a,
      which can then trigger allergic inflammation. The relation of these anaphylatoxin
      levels to clinical allergic disease responses is not known. OBJECTIVE: To
      evaluate the relationship of plasma CSP levels to allergic respiratory disease
      variables in an adult cohort. METHODS: A cross-sectional survey was used to
      assess the association of plasma C5a desArg and C3a desArg levels with clinical
      allergic respiratory disease variables. Furthermore, a time course of the effect
      of routine allergen immunotherapy on plasma CSP levels and cutaneous and
      pulmonary responses was determined. RESULTS: Adult plasma C5a desArg levels
      correlate with asthma severity as determined by a physician (P = .01) and by
      Asthma Quality of Life Questionnaire scores (P < .01). Change in plasma C5a
      desArg levels 1 hour after immunotherapy is associated with baseline
      rhinoconjunctivitis symptom severity (P = .03), change in total mean wheal
      diameter (P = .05), and total dust mite dosage (P = .04). Change in plasma C3a
      desArg levels 3 hours after immunotherapy correlates with change in total mean
      wheal diameter induced by dust mite (P = .01). Change in plasma CSP levels after
      immunotherapy did not correlate with change in spirometric outcome. CONCLUSIONS:
      Plasma C5a desArg levels reflect allergic respiratory disease severity as
      assessed by physicians and correlate with Asthma Quality of Life Questionnaire
      scores. Changes in CSP levels after immunotherapy reflect cutaneous allergic
      responses, especially to dust mite allergen.

PMID- 20143645
TI  - Treatment of episodes of hereditary angioedema with C1 inhibitor: serial
      assessment of observed abnormalities of the plasma bradykinin-forming pathway and
      fibrinolysis.
AB  - BACKGROUND: Hereditary angioedema (HAE) is typically the result of a deficiency
      of C1 inhibitor (C1-INH) with gene defects that lead to diminished plasma levels
      or the production of a dysfunctional protein. Replacement therapy with C1-INH has
      been shown to be effective in ameliorating episodes of swelling. We have reported
      elevated baseline levels of bradykinin, C4a, and plasmin-alpha2-antiplasmin
      complexes in the plasma of patients with HAE compared with the plasma of healthy
      controls. The production of factor XII fragment on in vitro activation of plasma
      with HAE has also been observed. OBJECTIVE: To perform serial assessment of
      abnormalities of the bradykinin-forming pathway and fibrinolysis in patients with
      HAE after treatment of episodes of swelling with intravenous C1-INH. METHODS: We
      obtained samples of plasma from 9 patients with HAE at a quiescent period
      (baseline), during an attack of swelling, and at 1, 4, and 12 hours after
      termination of an infusion of C1-INH. Factor XIIa, kallikrein, and plasmin were
      each measured by cleavage of synthetic substrates specific for each item.
      RESULTS: Each enzyme was strikingly elevated at baseline compared with the levels
      in pooled healthy plasma, and there was a progressive decline of activity to
      normal for factor XIIa and plasmin. Kallikrein decreased in 7 of the 9 patients
      at 1 hour and then decreased in all patients. Bradykinin levels were elevated at
      the outset in all patients, increased prominently during an attack of swelling,
      decreased to baseline after 1 hour, and then decreased toward normal by 4 and 12
      hours. CONCLUSION: The plasma levels of factor XIIa, kallikrein, and bradykinin
      decreased when measured serially subsequent to the infusion of nanofiltered C1
      INH.

PMID- 20143646
TI  - Anaphylaxis in the obstetric patient: analysis of a statewide hospital discharge
      database.
AB  - BACKGROUND: Previous reports of anaphylaxis during pregnancy typically have
      involved single institutions and a few cases. OBJECTIVE: To describe the
      epidemiologic features of anaphylaxis in women who gave birth in Texas. METHODS:
      Statewide public use hospital discharge data for 2004 and 2005 provided by the
      Texas Department of State Health Services were accessed. Diagnoses and procedures
      in this data set were recorded using International Classification of Diseases,
      Ninth Revision, Clinical Modification codes. The records of women who delivered a
      neonate and simultaneously had a diagnosis of anaphylaxis were selected for
      study. The prevalence of maternal anaphylaxis noted at the time of delivery of
      the neonate and the 95% Wilson's confidence interval were calculated. The
      International Classification of Diseases, Ninth Revision, Clinical Modification E
      codes were examined to determine the possible anaphylactic trigger. Finally, the
      impact of 4 selected maternal comorbidities and complications on length of stay
      was assessed. RESULTS: A total of 19 maternal anaphylaxis cases were identified.
      The prevalence was 2.7 cases per 100,000 deliveries (95% confidence interval, 1.7
      4.2 cases per 100,000 deliveries). Penicillins and cephalosporins were the
      anaphylactic trigger in 11 of the patients. Five patients were emergent
      admissions. There were no maternal deaths. Most of the patients (14 [74%])
      delivered by cesarean section. Patients who had 1 or more of 4 selected
      comorbidities or complications had a median length of stay of 5 days, whereas
      those patients free of these conditions had a median length of stay of 3 days (P
      = .07, exact Wilcoxon rank sum test). CONCLUSIONS: Anaphylaxis during pregnancy
      is a rare event. In this large case series, we found that beta-lactam antibiotics
      were the most common triggers of anaphylaxis.

PMID- 20143647
TI  - Role of food labels in accidental exposures in food-allergic individuals in
      Canada.
AB  - BACKGROUND: Little is known about the impact of food labeling on the allergic
      consumer. OBJECTIVE: To determine the proportion of food-allergic individuals
      attributing an accidental exposure to inappropriate labeling, failure to read a
      food label, or ignoring a precautionary statement and to identify factors
      associated with accidental exposures. METHODS: Food-allergic individuals or their
      caregivers were recruited from a Canadian registry of individuals with a
      physician-confirmed diagnosis of peanut allergy and from allergy awareness
      organizations. Participants completed questionnaires regarding accidental
      exposures due to specific food labeling issues. The association between
      accidental exposures and characteristics of food-allergic individuals or their
      caregivers was estimated using multivariate logistic regression models. RESULTS:
      Of 1,862 potential participants, 1,454 (78.1%) responded. Of the 47.8% (95%
      confidence interval [CI], 45.1%-50.5%) of respondents who experienced an
      accidental exposure, 47.0% (95% CI, 43.1%-50.9%) attributed the event to
      inappropriate labeling, 28.6% (95% CI, 25.1%-32.2%) to failure to read a food
      label, and 8.3% (95% CI, 6.3%-10.7%) to ignoring a precautionary statement. Food
      allergic individuals who were allergic to peanut, tree nut, fish, or shellfish
      were less likely to experience an accidental exposure due to the allergen not
      being identified in plain language. CONCLUSIONS: A considerable proportion of
      accidental exposures are attributed to inappropriate labeling, failure to read
      labels, and ignoring precautionary statements. Clear and consistent labeling of
      food allergens combined with increased consumer education is necessary to improve
      consumer confidence and compliance and to reduce accidental exposures.

PMID- 20143648
TI  - Eotaxin-2/CCL24 and eotaxin-3/CCL26 exert differential profibrogenic effects on
      human lung fibroblasts.
AB  - BACKGROUND: Eotaxin-2/CCL24 and eotaxin-3/CCL26 play an important role in
      eosinophil chemotaxis and activation in asthma. We previously demonstrated that
      eotaxin/CCL11 is profibrogenic for human lung fibroblasts. The effect of eotaxin
      2/ CCL24 and eotaxin-3/CCL26 on lung fibroblasts has not yet been investigated.
      OBJECTIVE: To evaluate whether eotaxin-2/CCL24 and eotaxin-3/CCL26 modulate
      fibrotic properties of lung fibroblasts. METHODS: Fibroblast proliferation was
      evaluated by means of 3-hydroxythymidine incorporation. Collagen production was
      assessed by means of 3-hydroxyproline incorporation and biochemical staining.
      Chemotaxis was determined using Boyden chambers. Expression of alpha-smooth
      muscle actin was evaluated by means of immunostaining. Transforming growth factor
      beta1 release was assessed using enzyme-linked immunosorbent assay. Parametric
      analysis of variance, followed by the Tukey-Kramer multiple comparisons test, was
      used to calculate statistical significance. RESULTS: Eotaxin-2/CCL24 but not
      eotaxin-3/CCL26 stimulated human lung fibroblast proliferation and collagen
      synthesis. In contrast, eotaxin-3/CCL26 but not eotaxin-2/CCL24 promoted
      fibroblast migration. Neither eotaxin-2/CCL24 nor eotaxin-3/ CCL26 induced the
      expression of alpha-smooth muscle actin or transforming growth factor beta1 from
      lung fibroblasts. CONCLUSIONS: Eotaxin-2/CCL24 and eotaxin-3/CCL26 have
      differential profibrogenic effects on human lung fibroblasts. These CC chemokines
      may, therefore, contribute to airway remodeling in asthma.

PMID- 20143649
TI  - Allergen immunotherapy-induced biphasic systemic reactions: incidence,
      characteristics, and outcome: a prospective study.
AB  - BACKGROUND: An anaphylactic reaction is one of the alarming adverse effects of
      allergen immunotherapy. Although a systemic reaction can follow a biphasic
      course, its incidence, its outcome, and the risk factors for its development are
      unknown in patients treated with immunotherapy. OBJECTIVE: To record the
      incidence, characteristics, and outcome of immunotherapy-inflicted biphasic
      reactions (BRs). METHODS: All patients attending large in-hospital allergy
      clinics for immunotherapy were followed up prospectively. Recorded patient data
      included the following: demographics, diagnosis, type and phase of immunotherapy,
      and peak expiratory flow (PEF) before each administration of the injections. If
      an anaphylactic reaction occurred, medical treatment was recorded and the patient
      was asked to complete a 3-day diary that included symptoms and periodic
      measurements of PEF. A BR was defined as a late decrease in PEF of more than 20%,
      with or without accompanying symptoms. RESULTS: During 10,040 visits, 453
      patients received 21,022 immunotherapy injections and 131 anaphylactic reactions
      occurred. Of these reactions, 11 (10%) were biphasic. Most uniphasic reactions
      (URs) and all BRs occurred in patients who were being treated for allergic
      rhinitis. A low baseline PEF or concomitant asthma was more common in patients
      with BRs. Other parameters were comparable between patients with URs and BRs. All
      BRs were mild and resolved either spontaneously or with oral antihistamines.
      CONCLUSIONS: Immunotherapy-induced BRs are uncommon. They tend to be mild and
      might be more common in patients with a low baseline PEF or concomitant asthma.
      Therefore, a long observation after the initial reaction is not required.

PMID- 20143650
TI  - Allergen immunotherapy and health care cost benefits for children with allergic
      rhinitis: a large-scale, retrospective, matched cohort study.
AB  - BACKGROUND: Children with allergic rhinitis (AR) often experience significant
      impairment in quality of life and health, which increases health care
      utilization. OBJECTIVE: To determine whether allergen immunotherapy reduces
      health care utilization and costs in children newly diagnosed as having AR using
      a retrospective matched cohort design. METHODS: Among children (age <18 years)
      with a Florida Medicaid paid claim between 1997 and 2007, immunotherapy-treated
      patients were selected who had newly diagnosed AR, who had not received
      immunotherapy before their first (index) AR diagnosis, who had received at least
      2 immunotherapy administrations after their index AR diagnosis, and who had at
      least 18 months of data after their first immunotherapy administration. A control
      group of patients with newly diagnosed AR who had not received immunotherapy
      either before or subsequent to their index AR diagnosis also were identified, and
      up to 5 were matched with each immunotherapy-treated patient by age at first AR
      diagnosis, sex, race/ethnicity, and diagnosis of asthma, conjunctivitis, or
      atopic dermatitis. RESULTS: Immunotherapy-treated patients had significantly
      lower 18-month median per-patient total health care costs ($3,247 vs $4,872),
      outpatient costs exclusive of immunotherapy-related care ($1,107 vs $2,626), and
      pharmacy costs ($1,108 vs $1,316) compared with matched controls (P < .001 for
      all). The significant difference in total health care costs was evident 3 months
      after initiating immunotherapy and increased through study end. CONCLUSIONS: This
      study demonstrates the potential for early and significant cost savings in
      children with AR treated with immunotherapy. Greater use of this treatment in
      children could significantly reduce AR-related morbidity and its economic burden.

PMID- 20143651
TI  - Rupatadine and its effects on symptom control, stimulation time, and temperature
      thresholds in patients with acquired cold urticaria.
AB  - BACKGROUND: Patients with acquired cold urticaria (ACU) show itchy wheals during
      cold exposure. This disturbing condition involves histamine and platelet
      activating factor in its pathogenesis. Rupatadine is a dual antagonist of both
      histamine and platelet-activating factor. OBJECTIVE: To assess rupatadine
      efficacy in preventing reactions to cold challenge in patients with ACU. METHODS:
      A crossover, randomized, double-blind, placebo-controlled study in which 21
      patients with ACU received rupatadine, 20 mg/d, or placebo for 1 week each is
      presented. The main outcome was the critical stimulation time threshold (CSTT)
      determined by ice cube challenge. Secondary outcomes included CSTT and the
      critical temperature threshold assessed by a cold provocation device (TempTest
      3.0), as well as scores for wheal reactions, pruritus, burning sensations, and
      subjective complaints after cold challenge. RESULTS: After rupatadine treatment,
      11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions
      after ice cube provocation). A significant improvement in CSTT compared with
      placebo was observed after ice cube and TempTest 3.0 challenge (P = .03 and P =
      .004, respectively). A significant reduction of critical temperature threshold (P
      < .001) and reduced scores for cold provocation-induced wheal reactions (P =
      .01), pruritus (P = .005), burning sensation (P = .03), and subjective complaints
      (P = .03) after rupatadine treatment were also found. Mild fatigue (n = 4),
      somnolence (n = 1), and moderate headache (n = 1) were reported during active
      treatment. CONCLUSION: Rupatadine, 20 mg/d, shows high efficacy and is well
      tolerated in the treatment of ACU symptoms.

PMID- 20143652
TI  - Skin-deep clues to a complex disease.

PMID- 20143653
TI  - Latex: a hidden occupational allergen.

PMID- 20143654
TI  - Maintenance of remission with low-dose omalizumab in long-lasting, refractory
      chronic urticaria.

PMID- 20143655
TI  - Allergy to prairie dog lipocalins.

PMID- 20143656
TI  - Allergy to pumpkin with cyclophilin as the relevant allergen.

PMID- 20143657
TI  - Investing in an electronic health record. Stimulus money is available--here's how
      to qualify.

PMID- 20143658
TI  - The Paladin thermostat 900 blood and solution warmer. The heat is on.

PMID- 20143659
TI  - Hazard report. Infants may fall through insecure ports on incubators.
AB  - If the iris ports or access ports on infant incubators are not sufficiently
      secure, infants may work their way through the ports and fall. To reduce this
      risk, users should make sure that the ports are closed securely following each
      use. When possible, users should pass tubing through the incubator hood's
      grommets instead of through the larger and potentially less secure iris ports.

PMID- 20143660
TI  - Hazard report. Don't use industrial-grade gases for clinical applications.
AB  - The use of industrial-grade gases instead of medical-grade gases for clinical
      applications increases the risk of introducing undesirable and even toxic
      contaminants into the clinical environment. Hospitals should have policies in
      place to ensure that gases of the appropriate type and grade are used for the
      intended application.

PMID- 20143661
TI  - FDA speaks out on the Steris System 1 and on CT dose risks--ECRI institute
      responds.

PMID- 20143662
TI  - Trial and error.

PMID- 20143663
TI  - Comparative effectiveness.

PMID- 20143664
TI  - New approaches to board chair effectiveness.

PMID- 20143665
TI  - The root of the problem. Interview by Mary Grayson.

PMID- 20143666
TI  - Action, advocacy and ideas.

PMID- 20143667
TI  - What's next for governance?

PMID- 20143668
TI  - The governance imperative for nonprofit hospitals.

PMID- 20143669
TI  - Bringing patients into the boardroom.

PMID- 20143670
TI  - [Clinical analysis of Mycobacterium abscessus pulmonary infection in our
      hospital].
AB  - OBJECTIVE: We analyzed the clinical characteristics of pulmonary infection due to
      Mycobacterium abscessus. MATERIALS AND METHODS: Four cases diagnosed with M.
      abscessus pulmonary infection encountered at Kawasaki Medical School Hospital and
      affiliated hospitals over the last five years were enrolled in this study. They
      all satisfied the diagnostic criteria of the Japanese Society for Tuberculosis.
      The clinical findings in this study were also compared to those of previously
      reported cases in Japan. RESULTS: The average age of the four cases was 56 years
      (one male and three females). All four cases showed underlying diseases,
      comprising two cases with malignancy, one with old pulmonary tuberculosis and one
      with collagen vascular disease receiving immunosuppressive treatment. Three cases
      were detected based on clinical symptoms, and one was incidentally identified
      during follow-up for another underlying disease. Laboratory examinations revealed
      mild or moderate inflammatory responses in three of the four cases, and three of
      the four were smear-positive for acid-fast bacilli in the clinical specimens
      (sputum in one and bronchial alveolar lavage fluid in two) microbiologically. The
      radiological examination revealed that one case showed tuberculosis resembling a
      cavitary lesion and three showed the small nodular and bronchiectatic type. The
      extent of lesions was within the unilateral lung in all cases. Concerning
      treatment for M. abscessus pulmonary infection, combined multi-drug chemotherapy
      using IPM/cs, AMK, CAM, and LVFX was carried out in three of the four cases,
      achieving a satisfactory clinical effect. However, one case died due to
      progression of the underlying disease before the initiation of treatment.
      CONCLUSION: Although M. abscessus pulmonary infection was more frequent in cases
      with underlying disease, the early, appropriate administration of antibiotics was
      performed in two of the four cases correctly diagnosed using bronchoscopic
      procedures, resulting in clinical improvement.

PMID- 20143671
TI  - Fighting the tuberculosis epidemic in the Western Pacific region: current
      situation and challenges ahead.
AB  - INTRODUCTION: Tuberculosis (TB) remains a major public health problem in the
      Western Pacific Region. More than 20% of the global burden of TB is found in the
      Region. In 2007, the latest year for which data is available, there were an
      estimated 1.9 million incident cases (109 per 100,000 population). Four countries
      (Cambodia, China, the Philippines and Vietnam) account for 93% of the total
      estimated incident cases in the Region. Every year an estimated 300 thousand
      persons die due to TB. The Region is host to an estimated 135,000 multi-drug
      resistant TB cases, most of which can be found in China. TB PREVALENCE AND TB
      MORTALITY: The Regional Stop TB strategy aims to halve the prevalence and
      mortality rates of 2000 by 2010. Based on current estimates, the TB prevalence
      declined with 24% between 2000 and 2007, while TB mortality declined with 19% in
      the same period. Given the current annual decrease in TB prevalence and
      mortality, it is unlikely that the Region will achieve the 50% reduction by 2010.
      CASE FINDING: Approximately 1.4 million new TB cases were notified in the Region
      in 2007, of which close to 0.7 million smear-positive cases. Cases from China
      accounted for 70% of the total notified smear-positive cases. The Regional case
      detection rate was sustained at 78%. Case detection rates in China, the Lao
      People's Democratic Republic, Mongolia, the Philippines and Vietnam exceeded the
      70% target. TREATMENT OUTCOMES: A total of 92% of the 0.7 million new pulmonary
      smear-positive cases registered for treatment in 2006 were successfully treated.
      The treatment success rates exceed the 85% target in all countries with a high
      burden of TB, except Papua New Guinea where it was reported at 73%. MULTIDRUG
      RESISTANT TB: In 2007, the proportion of MDR-TB in new TB cases was estimated to
      be 4%. A total of 135,411 MDR-TB cases was estimated to have occurred in 2007.
      Based on the overall case management data, 10,231 new patients and 1,596 re
      treatment patients were reported with available drug susceptibility testing (DST)
      results in the Region. Of these, 1% (89/10,231) and 29% (468/1,596) had MDR-TB,
      respectively. Capacity to detect and treat MDR-TB cases is still very limited in
      most countries in the Region. Eighteen countries and areas in the Region have
      conducted drug resistance surveillance (DRS) since 2000, according to the Global
      Project on Anti-tuberculosis Drug Resistance Surveillance. Among new TB cases,
      the prevalence of multidrug-resistant TB (MDR-TB) ranged from 0% in Cambodia to
      11.1% in the Commonwealth of the Northern Mariana Islands. MDR-TB prevalence
      among re-treatment cases ranged from 3.1% in Cambodia to 27.5% in Mongolia. In
      the five countries with a high burden of TB with available data from surveys
      (Cambodia, China, Mongolia, the Philippines, and Vietnam), MDR-TB prevalence in
      new cases and re-treatment cases ranged from 0% in Cambodia to 4.9% in China and
      from 3.1% in Cambodia to 27.5% in Mongolia, respectively. Notably, there were
      alarming rates of MDR-TB in several provinces in China among both new and
      retreatment cases. Increasing numbers of MDR-TB cases are reported from Papua New
      Guinea. TB-HIV CO-INFECTION: The overall estimated prevalence of HIV in new TB
      cases in 2007 was 2.7%. With 8.0% in 2008 compared to 11.8% in 2003, Cambodia
      shows a declining prevalence of HIV in new TB cases. There was a significant
      increase in the use of anti-retroviral therapy (ART) in the Region. However,
      detailed and complete data as well as strong collaboration in HIV and TB
      management are needed to be able to closely monitor the use of ART and its impact
      on TB-HIV co-infection in the Region. CONCLUSION: In spite of the substantial
      progress made in most countries with a high burden of TB, substantial challenges
      remain in the Region. The rate of decline in TB prevalence and mortality is too
      low to reach the 50% reduction goal in 2010. It will be necessary to further
      increase TB case detection and address the emerging spread of drug-resistant TB.
      The slow response in the most affected countries in the Region is a cause for
      concern. Strong commitment by national governments and their partners is needed
      to sustain and further strengthen the current TB control efforts.

PMID- 20143672
TI  - [Molecular and neuronal mechanisms of drug addiction].
AB  - Drug addiction is believed to be a chronic and convertible disease resulting in
      the obtrusive aim of drugs ingestion and the use of them in spite of health risk
      and life threat. Human behavior is mainly a resultant force of 3 actions of the
      functional CNS: arousal, reward and cognition. In addition all of them are
      advanced in the development of drug addiction. For the proper functioning of
      every complex system it is essential to maintain a proper communication of the
      elements it is made out of. Therefore the purpose of the paper was to present
      research results connected with consecutive chain links advanced in the flow of
      neuronal information. Considering the mechanisms of the formation of addictions
      recent research draws attention not only to the neuronal role of mezolimbical
      dopaminergic transmition, but also to the anatomical ground which is the limbic
      system (localization of the reward system) in the addiction progress. The
      stimulation of that structure results from catecholamines action, especially
      dopamine and serotonin, however, endogenic opioid peptides have a modulating
      effect. The research that is being conducted brings proof that psychostimulant
      agents may result in the release of adequate neurotransmitters or imitate their
      influence to the reward system. An important role in the addiction progress play
      the intracellular transmition mechanisms starting from receptors, through protein
      G, cyclic AMP and transcription factors. The latter factors may change target
      genes synthesis resulting in long-term claimed changes. In spite of the
      discussion about the possibilities of molecular and theoretical examinations,
      obtained effects transfer for practical applications, there are several non
      questioned advances like: recognition of cellular adaptation mechanisms,
      identification of reactions connected with reoccurrence after abstinence period,
      and possibilities of practical assessment of this knowledge in the dependence
      pharmacotherapy.

PMID- 20143673
TI  - [Homicides in recent years researched in cooperation with "Archiwum X"].
AB  - In the paper 5 cases of hiding corpses after homicides were presented, in two
      cases corpses were buried, in two cases walled up inside buildings and in one
      case burned down. Time period between homicide and corpse finding was from one
      year to 14 years.

PMID- 20143674
TI  - [The issue of expert opinions in underage pornography materials involving
      underage persons below 15 years of age].
AB  - The number of cases in which the estimation of age of the persons pictured in
      pornography materials is mandatory has been increasing for the last few years.
      The aim of the publication was to indicate the possibilities which are currently
      available for the forensic experts in this matter. The ones published heretofore
      mainly had focused on the difficulties which are inseparable elements of such
      expertise. Current publication has a demonstrative character and has been based
      upon the experience of two Forensic Medicine Departments. Such expertise have
      been constantly prepared in both of them for the last few years and none of them
      had to be changed till now. The currently available methods which allow for age
      estimation of the persons upon their photographical and movie images are far from
      perfection. Still authors remain skeptic about the possibility that significant
      progress in that matter can be achieved in predictable future. In such situation
      the most effective application of existing techniques becomes essential to
      minimize the risk of false-positive and false-negative results from appearing.
      Some of the difficulties pointed out by other authors are not important in
      practice.

PMID- 20143675
TI  - [Evaluation of Powerplex Y system in genotyping of male component after sexual
      intercourse].
AB  - Y-STRs are of an importance in forensic genetics in cases of selective genotyping
      of male haplotypes and/or determination of a number of perpetrators. Experimental
      vaginal swabs containing semen were collected to evaluate the effect of storage
      conditions and male/female DNA ratio on the efficiency of amplification of
      Powerplex Y system alleles. The specimens were collected on disposable devices
      from 20 volunteer pairs of sexual partners. The swabs were stored on selected
      supports in different temperature conditions. DNA templates were extracted using
      Chelex and quantitated spectrophotometrically. Powerplex Y system (Promega) ABI
      Prism 310 (Applera) were used to obtain Y-STR profiles. Vaginal swabs airdryed at
      room temperature were found the best source of DNA for male identification. Full
      Y-STR haplotypes were obtained in male/female mixtures prepared in proportion of
      1 : 1000.

PMID- 20143676
TI  - [Medico-legal assessment of medical malpractice in ambulance service based on the
      casework material collected at the Department of Forensic Medicine, Medical
      University of Bialystok].
AB  - INTRODUCTION: Emergency medical personnel is particularly concerned about medical
      malpractice. The objective of the paper was the analysis of casework material
      assessed at the Department of Forensic Medicine, Medical University of Bialystok
      in the years 2001-2006 for medical malpractice by ambulance service staff.
      MATERIAL AND METHODS: A total of 80 opinions assessing improper treatment and
      diagnostic procedures and the problem of withdrawal and organizational
      malfunction was reviewed. RESULTS: Medical malpractice was concluded in 38
      (47.5%) cases analysed. In 22 cases malpractice of ambulance staff resulted in
      patients' demise. Most of cases included improper diagnosis of patient's
      condition. Predominantly, misdiagnosed cases were related to circulatory, nervous
      and respiratory malfunctions. Diagnostic errors caused by young and inexperienced
      medical doctors accounted for most of malpractice in the material analysed.
      CONCLUSIONS: It is concluded, that medical doctors are inadequately prepared to
      differential diagnostics of pathologies. Errors caused by ambulance dispatchers
      included denials of service in life threatening cases.

PMID- 20143677
TI  - [Medico-legal assessment in neurosurgical malpractice based on the material
      collected at the Department of Forensic Medicine, Medical University of
      Bialystok].
AB  - INTRODUCTION: Medical malpractice results from inadequate professional knowledge,
      incompliance to the present state of medical knowledge or negligence and
      inattention. The aim of the paper was the analysis of diagnostic and therapeutic
      malpractice based on casework material in the field of neurosurgery. MATERIAL AND
      METHODS: Medical malpractice cases were assessed according to the number and type
      in 25 medico-legal opinions issued by the Department of Forensic Medicine,
      Medical University of Bialystok in years 2001-2006. RESULTS: Majority of cases
      were craniocerebral injuries related to delayed diagnostics, incorrect treatment
      including withdrawn or improper surgery. In 5 cases (20%) medical malpractice was
      concluded. In 2 cases the death of patients was pronounced. In most cases medical
      malpractice was attributed to lacked or delayed diagnostics and improper
      technique during spinal surgery. CONCLUSIONS: Relatively limited number of
      malpractice concluded may support correct knowledge and competence of medical
      doctors. Maximum attention should be kept during the examination of patients
      after general trauma, with special consideration of potential intracranial
      injuries. Diagnostic difficulties result from acute supradural hematomas.

PMID- 20143678
TI  - [Medico-legal assessment in neurological malpractice based on casework material
      collected at the Department of Forensic Medicine, Medical University of
      Bialystok].
AB  - Medical malpractice results from inadequate professional knowledge, incompliance
      to the present state of medical knowledge or negligence and inattention. The aim
      of the paper was the analysis of medical malpractice cases based on material in
      the field of neurology. The cases were assessed according to the number and type
      in 32 medico-legal opinions issued by specialist teams of forensic medicine and
      neurology in the Department of Forensic Medicine, Medical University of Bialystok
      in the years 2001-2006. In 11 cases (34%) medical malpractice was concluded with
      reference to improper treatment after head injury or brain pathology, inadequate
      care at neurology unit, lacked or delayed diagnostics of head pathology and
      injury, non-referral to hospital by neurologists. In the material analysed
      diagnostic errors predominated. Majority of them originated from the open health
      care system. Incompetence of neurologists with regard to differential diagnostics
      resulting in misdiagnosis and improper therapy was noted. In one third of the
      overall cases medical malpractice was concluded. The most common causes included
      misinterpretation of disease signs and symptoms, misapplication of available
      diagnostic potential and unjustified delay before commencing diagnostics.

PMID- 20143679
TI  - [Medico-legal assessment in civil lawsuit concerning patients with neurological
      disorders].
AB  - INTRODUCTION: The objective of medico-legal assessment in civil lawsuit involves
      the assessment of health impairment due to a cause under dispute, evaluation of
      percentage health impairment, assessment of relationship between the cause and
      the impairment. The objective of the paper was the analysis of medicolegal
      opinions ordered by civil departments of courts in Poland involving patients with
      neurological disorders. MATERIAL AND METHODS: The examination criteria included
      age, sex, type of accident, type of injury and symptoms reported, causative
      relationship and ability to work. The study comprised 36 civil opinions issued by
      the Department of Forensic Medicine, Medical University of Bialystok in the years
      2001-2003. RESULTS: State of consciousness was assessed at the moment of making
      important decisions or signing important documents, ability to work, causative
      relationship between the accident and symptoms reported. Moreover, suitability of
      treatment was evaluated. No significant differences regarding sex were found
      between plaintiffs. Occupationally active persons were predominantly subject to
      injuries. The most common symptoms reported were headache, vertigos and aching
      pain in the L-S spine. CONCLUSION: No therapeutic incorrectness was found in
      cases under analysis. In 7/12 cases health impairment was assessed. In 75% of the
      opinions no cause-effect relationship was concluded between current disorders and
      accident at work.

PMID- 20143680
TI  - [Changes in autopsy findings related to reanimation procedures--case report].
AB  - Reanimation procedures may cause changes of autopsy findings. Disregarding this
      condition may result in erroneous determination of the cause of death. The paper
      presents a case of a woman, age 77, complaining of general weakness who reported
      to the outpatient department. Paroxysmal tachycardia was diagnosed on EKG. The
      patient was referred to the internal ward. The transfer to the hospital was
      offered by the neighbour who had brought her to the outpatient department. In
      front of the department the patient fainted. Reanimation was performed by 5
      persons, including non-medical staff. The patient's death was pronounced within
      an hour. The autopsy findings included numerous injuries within the thorax and
      the abdomen, which aroused suspicion about their origin during reanimation and
      about the cause of death. Detailed analysis of medical history, witness
      testimonies and histological findings, taking into account the knowledge about
      potential changes caused by reanimation procedures enabled correct assessment of
      injuries within the thorax and the abdomen.

PMID- 20143681
TI  - [The analysis of road accident victims aging between 0-18 in the selection
      material of the our Forensic Department, Medical University of Bialystok between
      1997-2006].
AB  - INTRODUCTION: The authors carried out the analysis of autopsy reports of road
      accident victims, aging between 0-18, exposed to the post mortal studies made in
      the above mentioned department between 1997-2006. MATERIAL AND METHODS: The
      number of victims, aging between 0-18 amounts to 2.97% of all autopsies carried
      out in this period. Among the analysed 84 victims were male, while 41 female. The
      victims have been divided into age groups: 0-6, 7-10, 11-15 and 16-18. The
      largest number appeared in the age range 15-18 (78; 47 males and 31 females), the
      smallest number in the age range 0-6 (15; 10 males and 5 females) and the age
      range 7-10 (15; 12 males and 3 females). In the age groups 0-6 and 7-10
      pedestrians prevail as victims, while 11-15 car passengers are in majority and
      the same percentage refers to cyclists. Group 16-18 is predominantly dominated by
      private car drivers and their passengers. RESULTS: In all age groups the direct
      causes of death were mainly head injuries, the most frequent among pedestrians,
      cyclists, two wheeled engine vehicle passengers, drivers and private car
      passengers as well as other victims of not exactly defined road accidents. The
      most alarming is the high percentage of road users under the influence of alcohol
      in the range 16-18 amounting to 21.8 % (27.7% of males and 12.9% of females
      respectively).

PMID- 20143682
TI  - [Analysis of suicide causes in the material of Bialystok Forensic Medicine
      Department in the years 2004-2006].
AB  - PURPOSE: The object of analysis were suicide cases autopsied in the department in
      2004-2006. MATERIAL AND METHODS: Of the 1331 autopsies, 126 were undertaken in
      suicide victims. This number constituted 9.47% of the total number of autopsies,
      of those 87.3% were males and 12.7% females. The highest percent rate of suicide
      was observed among males in the ages of 19-25 year old, among females 19-25 and
      31-45. The greatest number of inebriated males was found in ages of 19-25 and 36
      40 years old, whereas for females the corresponding age group was 31-35 years.
      Among the places of suicide predominance of public places was noted. The most
      common method of committing suicide was by hanging.

PMID- 20143683
TI  - [Cases of suspected pediatric malpractice in casework material collected at the
      Department of Forensic Medicine, Medical University of Bialystok in the years
      2001-2006].
AB  - The authors analysed medico-legal opinions issued by teams of expert witnesses in
      the Department of Forensic Medicine, Medical University of Bialystok. In the
      years 2001-2006 a total of 698 opinions in cases of suspected medical
      malpractice, including 44 (6.3%) pediatric cases, were issued. The opinions were
      ordered by police (9.3%) and prosecutors (90.7%). Medical malpractice was
      suspected in 20% of cases involving emergency procedures, 20% of cases involving
      family doctor's procedures and about 60% of cases involving hospital procedures.
      Medical malpractice was concluded in 9 (20.4%) cases, including 4 fatal demises.

PMID- 20143684
TI  - [Sole guardian's death as a cause of his handicapped mother's death--a case
      report].
AB  - Finding more than one body in the place of residence brings suspicion of
      poisoning or action of a third party. The authors present a case of two bodies--a
      handicapped mother and her son--found in their own house. The son was last seen
      by their neighbours three days before the bodies were revealed. There was a stove
      in the house which was cold with no signs of penetration. No indication of a
      third party action was found on the corpses. The autopsy on the son revealed a
      heart attack with subsequent rupture and tamponade which resulted in death. The
      cause of the mother's death was assumed to be total starvation of the handicapped
      person deprived of care. In the presented case autopsy findings contributed to
      the assessment of the factual cause and sequence of the deaths.

PMID- 20143686
TI  - [Ethnic variation and forensic efficiency of selected microsatellite markers in a
      population of northeastern Poland].
AB  - INTRODUCTION: Objective of the research included calculation of biostatistical
      indexes and forensic efficiency parameters and deepening knowledge on genetic
      structure of the population considering historical background and ethnic
      composition. MATERIAL AND METHODS: Forensic genetic markers were typed in a total
      of 620 individuals in population samples of Poles and minorities of
      Byelarussians, Lithuanians, Polish Tatars and Old Believers. RESULTS: Genetic
      polymorphisms analysed using statistic methods may be informative in
      differentiation of populations and ethnic groups. Variation in distributions of
      genetic markers in northeastern Polish populations should be considered when
      evaluating matching probability of forensic evidence.

PMID- 20143685
TI  - [Medico-legal and victymology aspects of homicides in the material of Bialystok
      Institute of Forensic Medicine in the years 2004-2006].
AB  - The authors presented an analysis of homicides based on autopsy material
      collected at the Institute of Forensic Medicine Medical University of Bialystok
      in the years 2004-2006. Of 1331 postmortem examinations, this type of death
      accounted for 4.28% of cases, including 19,3% women and 80.7% men. Married
      persons predominated among females and men. 63.1% of victims died on the crime
      scene, 29.8% within 24 hours. In immediate conflicts, fights and robberies, the
      perpetrators most commonly employed hard, blunt or blunt-edged crime weapons. In
      cases of murder with sexual and robbery homicides the strangulation method was
      used. No seasonal character in homicide prevalence was observed.

PMID- 20143687
TI  - [Difficult species identification of cranial fragments--case report].
AB  - INTRODUCTION: An examination of remains found on the roadside in a locality near
      Lodz, Poland showed them to be cranial bones. Their general appearance, and
      particularly the significant curvature of the vault and dimensions indicating a
      relatively large skull capacity showed that they could be human remains. But
      against that notion spoke anatomical details such as the size of the frontal
      sinuses, the situation of probable zygomatic appendices of the frontal bone, the
      texture of the interior surface, atypical in human beings, and the progression
      and morphology of the cranial sutures. However, a comparative analysis of animal
      skulls did not result in any positive conclusion. The skull fragment was judged
      to have a significantly different morphology, possibly the effect of
      developmental abnormalities or disease processes. MATERIAL AND METHODS: To
      resolve the uncertainty, genotyping was carried out in human-specific STR
      sequences, and then in STR sequences using starter sequences specific for dogs,
      cattle, sheep, domesticated and wild swine. But to determine decisively the
      species of the remains, mitochondrial DNA analysis was performed using universal
      starters for the PCR--a conservative, species-specific region of the
      mitochondrial genome was analysed.

PMID- 20143688
TI  - [Sudden suffocation by clogging up of the respiratory tract with foreign bodies-
      case report].
AB  - The study presents a case of death by clogging up of the respiratory system by
      foreign bodies. The autopsy revealed among others the presence of a cigarette
      lighter and a piece of an aluminum spoon in the throat, and a cut-and-stab wound
      on the front surface of the neck with accompanying trial incisions, penetrating
      into the respiratory tract, clogged by a substantial amount of blood, focuses of
      aspiration in the lungs, and symptoms of lung distension. Histopathological
      examinations of inner organ samples revealed the presence of extravasations of
      blood in the air space as well as symptoms of acute lung distension, confirming
      the autopsy diagnosis. Toxicological examinations revealed that the victim in the
      moment of death was in a state of deep alcoholic intoxication. The conducted
      interrogations of possible witnesses/suspects of the incident turned out
      insufficient for the reconstruction of events. The authors of the study therefore
      attempt a reconstruction of the incident based on executed examinations.

PMID- 20143690
TI  - [Assessment of the possibilities of application of the thermovision technique in
      medico-legal diagnosis. Theoretical basis].
AB  - The authors in their work wish to prove that technological advancement of modern
      thermovision technique opens for forensic medicine, as an applied science, new
      diagnostic possibilities, especially in the scope of the post-mortem
      examinations. In the past, some attempts were already undertaken to apply
      thermovision techniques in forensic medicine, those tests, however, were not put
      in the everyday medical-legal practice. Most of the factors which have an
      influence in decreasing the value of thermograph tests are not present while
      biological material is tested post-mortem, therefore, paradoxically, natural
      elimination of obstacles occurs in such cases, which allows for medical-legal
      post-mortem diagnostics based on thermograph images. In particular, the most
      promising is active dynamic thermography which is based on the analysis of
      thermograms' sequence registered during transitional thermal processes in the
      examined object (heating or cooling of the object), which is stimulated by an
      external heat source, and the object's response to this stimulation is a change
      of the temperature which function in time determines its internal structure.
      Pathological and injury changes and their results in the form of structural
      damages of tissues lead to thermal conductivity and capacity which can be
      noticeable in a thermovision test. There are, then, no theoretical obstacles to
      the use of active dynamic thermography in post-mortem tests of tissues to
      evaluate their structure. With today's technological progress, it should be
      expected that in the near future sensitivity of thermovision appliances will
      significantly influence the increase of the specificity of obtained images. It
      can not be excluded that thermography methods could become a back-up method or
      even an alternative for other imagining methods.

PMID- 20143689
TI  - [The utility of the 16 Y-STRS markers in the central Poland population].
AB  - Haplotype and allele frequencies for the panel of 16 Y-chromosome STR loci,
      namely DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437,
      DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y GATA-H4 were determined in a
      population sample of 250 unrelated males from the central region of Poland. The
      238 different haplotypes were identified, of which 227 haplotypes were unique, 10
      were duplicated and one haplotype was shared between three unrelated men. The
      average gene diversity was 0.5995, combined gene diversity was 0.9998 and
      probability that two randomly chosen haplotypes are different in the population
      was 0.9996. Interpopulation comparisons revealed that Polish population is
      homogeneous within the three compared samples, while it differs statistically
      significantly from other population samples apart from Spanish population. This
      seems to be the first report showing the analysis of the molecular genetic
      distance between the population of Poland and other European and world
      populations for the panel of 16 Y-chromosome STR loci. The analyzed set of Y-STR
      markers is very useful in forensic casework to identify males and trace paternal
      lineages.

PMID- 20143691
TI  - [Application of thermovision in forensic medicine on the basis of the research
      carried out in Forensic Medicine Department, Pomeranian Medical University in
      Szczecin].
AB  - All solid bodies in the temperature above absolute zero emit electromagnetic
      radiation whose spectrum depends, among others, on temperature. Thermovision is
      the method which uses infrared cameras for recording infrared radiation emitted
      by human skin. The method is widely applied in medicine. In this study we want to
      present possible applications of the thermovision camera in forensic medicine (to
      investigate the decrease in the temperature of mortal remains; to study
      temperature distribution in the material simulating human body tissue exposed to
      the action of a bullet shot from firearms) as well as emphasize the necessity of
      establishing thermal norms as a potential source for comparative research.

PMID- 20143692
TI  - [Criminal methods in archaeology--collaboration between Forensic Medicine
      Department, Pomeranian Medical University and the Archaeological Museum in
      Gdansk].
AB  - INTRODUCTION: During excavation works carried in the Old Town by the
      Archaeological Museum in Gdansk, human remains were found which date back to the
      turn of the 12th and 13th centuries. On the basis of Gdansk townsmen's skulls,
      Forensic Medicine Department, Pomeranian Medical University (PAM) performed the
      skull based face reconstruction of 8 individuals. MATERIAL AND METHODS: In this
      study, we wanted to present possibilities of using Gierasimow reconstruction
      method for museum goals. Reconstruction is an anthropological method which aims
      at reconstructing bony elements of a skull and head soft tissue. The most
      commonly employed modern way of reconstruction is Gierasimow's method which is
      based on the observation of soft tissue thickness and its dependence on the form
      and level of development of different skull areas. Standards for tissue thickness
      were elaborated for various points (along the profile and transverse sections);
      they were based on the examination of soft tissue thickness performed on the
      corpse (for each sex separately). Deviations from the standards result from
      racial affiliation, age, and the level of development of adequate skull areas.
      The research scheme includes determination of sex and age, and collection of the
      detailed craniometrical and cranioscopic data with comprehensive description of
      the features which can affect the appearance of soft parts. After relevant
      measurements are done, the muscles are modeled. During the following stage, soft
      tissue thickness is marked in particular points as stalks and ridges. Next they
      are joined together to achieve the final effect of reconstruction. From this
      moment, finishing works are continued by a sculptor in cooperation with an
      anthropologist. CONCLUSIONS: The results of research conducted by
      anthropologists, anatomists, morphologists, physicians and criminologists are of
      great importance and they convey both cognitive and practical meaning.
      Reconstructions appeal to human imagination, and for that reason they are also
      addressed to non-professional audience.

PMID- 20143693
TI  - [Quantitative study of the relationship between age and digital histological
      image of human femur].
AB  - The relationship between the bone digital histomorphometry data of the femoral
      head and the age was investigated. Proximal femur samples were obtained from 31
      patients, during surgery for various orthopedic conditions. The histological
      section, through the fovea of the femoral head was taken. Tissue sections were
      decalcified and stained with haematoxilin and eosin. Those sections were used for
      further quantization. Histological image was scanned into the computer, using
      digital camera. With an image analysis computer program the following static
      measures were determined: number, area and circumference of trabeculas, bone
      marrow and empty spaces. Most parameters showed a weak association, when compared
      with age.

PMID- 20143694
TI  - [Carbon monoxide as an external cause of fatality].
AB  - INTRODUCTION: Carbon monoxide intoxications mainly occur as a result of fires in
      houses and failures of heating systems. Case of fatal accident involving a
      charcoal factory worker is described in this paper. MATERIAL AND METHODS: Authors
      based on a medico-legal autopsy protocol and material collected in prosecutor
      files. Medico-legal autopsy of a 46 year old male was performed in the forensic
      medicine department. Interlocutory proceedings indicated that the immediate cause
      of death was a head-crush caused by a hydraulic cover. Previously self-ignition
      in the factory was noted. RESULTS: Autopsy revealed crushes of cervical spine
      involving the medulla. Where there were no sings of carbon monoxide intoxication.
      Due to unusual circumstances of the accident (self-ignition was detected by a
      carbon monoxide sensor and was treated by steam) additional toxicological test of
      autopsy material was performed. Twenty percent of carboxyhemoglobin was detected
      in blood collected from the heart cavity. In our opinion carbon monoxide may have
      been responsible for the accident. CONCLUSIONS: Relatively low carboxyhemoglobin
      concentration in the blood is known to be an important cause of central nervous
      system abnormalities. Exposure to carbon monoxide may also result in an impaired
      response to danger. Sometimes carbon monoxide exposure does not lead to fatal
      intoxication, but may lead to a fatal accident. Regardless of a well noted
      immediate cause of death, a specific toxicological test must be involved in each
      medico-legal procedure, if exposition to various chemical substances is
      suspected.

PMID- 20143695
TI  - [Lawsuit experiment as an important element in expert's work regarding carbon
      monoxide poisoning cases].
AB  - INTRODUCTION: Giving an opinion in the field of carbon monoxide intoxications is
      still problematic. MATERIAL AND METHODS: In the paper we present a case of the
      sudden death of a young female in the garage. In such a situation there were
      serious suspicions of a violent cause of the death. According to eye-witness
      relation an experiment to evaluate momentary carbon monoxide concentration in the
      garage was conducted. The toxicokinetic and biologic effects of carbon monoxide
      were taken under consideration. RESULTS: It was revealed that under the given
      parameters it was impossible there to reach a lethal carbon monoxide
      concentration.

PMID- 20143696
TI  - [Carbon monoxide poisoning based on the autopsy material collected at the
      Department of Forensic Medicine, Medical University of Bialystok in the years
      2004-2006].
AB  - INTRODUCTION: The objective of the paper was the presentation of observations and
      conclusions based on the review of autopsy records collected at the Department of
      Forensic Medicine, Medical University of Bialystok in the years 2004-2006.
      MATERIAL AND METHODS: The criteria under evaluation included sex, age, alcohol
      level, carboxyhemoglobin concentration and site of poisoning. The COHb level was
      determined by the Wolff's method. CONCLUSIONS: In a total of 1331 autopsies 66
      (4.96%) cases of fatal carbon monoxide poisonings were reported, including 11
      females and 55 males (16.7% and 83.3%, respectively). The primary cause of
      poisoning were blazes in flats, houses and farm buildings (80.3%). Apparent
      seasonal pattern of poisoning incidences was found, with a significant increase
      in the fall-winter period. Mean COHb concentrations in females and in males were
      73.9% and 56.3%, respectively. The lowest COHb concentration (46%) was noted in
      the age group 0-10 years and the highest (75.5%) in the age group 41-50 years,
      which corresponds to the values reported previously. Fatalities included 23 sober
      persons (34.8%) with mean COHb 58.5% and 43 non-sober persons (65.1%) with mean
      COHb 57.0%. The prevalence of non-sober fatalities corresponds to the values
      reported previously. The highest concentrations of carboxyhemoglobin--67.2% and
      58.4%, were determined in the alcohol level ranged of 3.1-4.0 per thousand and
      1.1-2.0 per thousand, respectively, which only partly correspond to previous
      results.

PMID- 20143697
TI  - [Genetic polymorphisms of 10 STR (AmpFlSTR SGM Plus system) loci in Gypsy
      population from Poland].
AB  - INTRODUCTION: The aim of the paper was to create a database of the allele
      distribution at 10 STR loci (D3S1358, vWA, D16S539, D2S1338, D8S1179, D21S11,
      D18S51, D19S433, TH01, FGA). MATERIAL AND METHODS: The DNA were isolated from
      samples collected from 222 unrelated individuals of the Gypsy population from
      Poland. Amplification was performed using a commercial multiplex FlSTR SGM Plus
      kit. The amplified fragments were resolved by electrophoresis in a 5% denaturing
      polyacrylamid gel using tne ABI Prism 377 DNA sequencer. The expected performance
      of the analyzed loci for personal identification testing was estimated. RESULTS:
      All loci met the Hardy-Weinberg assumption. The combinated values of the matching
      probability (MP) and of the power exclusion (PE) are 3.95 x 10(-13) and
      0.9999641. CONCLUSIONS: Statistical parameters (PIC, MP, PE) showed that the
      examined systems are useful for forensic medicine.

PMID- 20143698
TI  - [Genetic identification of an osseous material dating from diverse historical
      periods].
AB  - INTRODUCTION: Bad quality and slender amount of the material at our disposal
      during identity examination and ever growing number of expired and difficult
      identity cases compelled us to examine: 1) amplification grade and amount of
      human DNA in degraded biological material originating from diverse environments
      and historical periods; 20 operating mode in case of biological material from its
      preparation through isolation, amplification till interpretation of the achieved
      results; 3) usefulness of the accepted identification and amplification method
      while creating an identification procedure pattern in case of strongly decayed
      material. MATERIALS AND METHODS: The research material were samples isolated
      from: bone fragments collected from grave crypts, bone fragments collected during
      autopsies performed in the Forensic Medicine Institute PMA and during
      exhumations. DNA isolation was done by means of modified osseous DNA preparation
      method proposed by Zoledziewska and Dobosz. DNA amount was determined by means of
      ABI PRISM 7900HT Sequence Detection System apparatus with the use of Quantifiler
      Human DNA Qualification Set. The samples were amplified by means of AmpFlSTR SGM
      Plus set and were separated electrophoretically in the ABI PRISM 310 apparatus.
      CONCLUSIONS: 1. Environmental conditions like humidity, temperature, subsoil and
      microorganisms putrefying the body have the greatest influence on the
      preservation and DNA degradation grade. 2. Low amplification of long DNA
      fragments testifies that in the future the analysis of degraded DNA would be made
      with the use of sets based on the short fragments: ca. 100 pz. 3. Time that
      elapses since death is of less significance when we take into account tissues
      exposed to unfavourable, multifactoral environmental influence. 4. The method
      used and introduced modifications can be freely utilised in identification cases
      when the material is strongly decayed, coming from victims of mass disasters,
      terrorist attempts, genocide and natural cataclysms when the use of standard
      methods is impedimented or impossible.

PMID- 20143699
TI  - [Examination over a foreign body left inside during an operation of a lumbar
      spine].
AB  - Procedure of an examination over a gauze swab removed during a repeated operation
      of a patient who had undergone earlier a neurosurgical operation of a lumbar
      spine has been described. The extracted gauze swab became an exhibit in a case at
      court for financial compensation. The court commissioned to explain "if it could
      be placed in another way than leaving it during the former surgical operation".
      The neurosurgeon who performed the former operation decidedly denied that the
      gauze swab in question could have been left by him. Hemogenetic and histologic
      examination gave basis to the statement that the exhibit was left inside during
      the former neurosurgical operation.

PMID- 20143700
TI  - [Concentration of selected microelements in blood serum of rats exposed to the
      action of psilocin and phenylethylamine].
AB  - Natural hallucinogens (including Psilocybe mushrooms) became popular in Europe
      since the nineties. They have been in the focus of clinicians interest for years
      because of their biological effects. Mechanism of action of these hallucinogens,
      both Psilocin and Psilocibin, is based on the physiological structure similarity
      to human neurotransmitters as serotonin and catecholamines. One of the previous
      works indicated the possibility of the cardiotoxic action of the Psilocibin
      mushroom, effecting in anoxemic heart laesure. To verify the hypothesis of the
      Psilocibin-like myocardial damage wide experimental programme was designed. In
      the present work we introduce some results concerning magnesium, calcium,
      natrium, kalium and chloride plasma concentration in rats subjected subchronicly
      to psilocin and phenylethylamine. Basing on the obtained results, it can be
      stated that subchronic intoxication with natural hallucinogens may disturb
      magnesium balance without significantly effecting other microelements.

PMID- 20143701
TI  - [Forensic biological traces as a "portrait" of perpetrators of murder and other
      offences].
AB  - INTRODUCTION: In the introduction remarks will be provided on inspections of the
      sites of murder or of other offences, conducted with the participation of a
      forensic physician or other experts of forensic biology. The goal of this paper
      is to make interested parties aware of the possibility of numerous biological
      traces and micro-traces found on the scenes of diverse crimes, which many a time
      are omitted. The presence of those traces prompts one to strive for
      individualised identification of perpetrators of murder based upon the material
      they leave behind. In case of problems with actual identification of a
      perpetrator there is a possibility of a group-wise identification, accompanied by
      the creation of one but specific version of the subject occurrence. Those type of
      actions may be carried out thanks to the application of modern investigation
      methods and materials at individual stages of looking at evidence. Furthermore, a
      whole procedural algorithm is developed, from discovering a biological trace
      through its technical and procedural preservation, inspections of the victim, and
      perpetrator and collection of comparative materials from both of them, selection
      of appropriate methods and measures till the eventual findings i.e.
      individualisation of man. In the paper morphologic properties of forensic
      material of human origin (tissues, secretions, excrements, nail and teeth
      scratches) will be exposed; the material will be classified and on that basis
      some pre-selected material will undergo further analyses with particular
      attention drawn to molecular researches. CONCLUSIONS: Conclusions will include
      the finding of biological micro-traces being often times omitted but which are of
      importance and thanks to currently applied equipment and genetic methods may lead
      to individual identification on the basis of a very small amount of evidential
      material collected.

PMID- 20143702
TI  - [Comparative tests of ethyl alcohol concentrations in blood, vitreous body of an
      eye and urine collected from a corpse].
AB  - In the work research into alcohol content in the vitreous body and blood
      collected from 290 corpses was done. A statistical analysis was carried out and
      it presented a high dependency between alcohol content in blood and in vitreous
      body, which gave grounds to the assumption that the vitreous body is a good
      material for marking ethanol post mortem in cases when collecting blood is
      impossible.

PMID- 20143703
TI  - [Population study of four X-chromosomal STR loci from the northern part of
      Poland].
AB  - INTRODUCTION, MATERIALS AND METHODS: The allele frequencies of four short tandem
      repeats (STR) loci specific to the human X chromosome (DXS101, DXS7423, DXS8377
      and phosphoribosyltransferase HPRTB) were analyzed by means of a multiplex PCR
      reaction in a sample of 200 unrelated individuals residing in the northern part
      of Poland. The separation and detection of PCR products were performed by
      capillary electrophoresis on the 3130 Genetic Analyzer. Testing for Hardy
      Weinberg equilibrium (HWE) showed no significant deviation for these loci.
      RESULTS: Statistical parameters such as: heterozygosity observed, mean exclusion
      chance, power of discrimination in males and power of discrimination in females
      showed that the examined multiplex is useful in forensic and paternity testing
      applications.

PMID- 20143704
TI  - [Biochemical skin sweat-sebum profile in individual identification].
AB  - INTRODUCTION: Sweat-sebum substance released by an individual, is left on the
      surface of different objects by direct contact (touch), which takes place in the
      well known mechanism of finger-print formation. Interesting from the crime
      detection point of view seems to be the determination of qualitative and
      quantitative changes in sweat-sebum biochemical profile left on objects, which
      may contribute to the determination of precise biochemical profiles in relation
      to individual identification. MATERIAL AND METHODS: Five different hand profiles
      of sweat-sebum were determined using gas chromatography with mass spectrometry
      obtaining referral material, then obtained profiles were compared to the profile
      left on a rough plastic surface by one individual belonging to the referral
      group. RESULTS: Obtained results indicate the possible application of the
      procedure for correlation of sweat-sebum skin profiles for identification
      purposes in crime detection, as indirect prove. Undoubtedly, although there is no
      possibility to show the uniqueness of particular profiles, like it is in a
      genetic examination, the short time needed to perform analysis (approximately 40
      min) is very significant in the presented procedure, which may be a
      complementation of genetic methods in case were short time of perpetrator typing
      is a crucial step. CONCLUSIONS: Presented procedure may be helpful in preliminary
      individual identification in case were there is no possibility to collect finger
      print profiles from the surface (inappropriate surface structure, smear traces).

PMID- 20143705
TI  - Taxonomical and numerical comparison of epipelic algae from Balik and Uzun
      lagoon, Turkey.
AB  - The epipelic algae of Balik lagoon and Uzun lagoon were investigated from May
      2003 to December 2004. A total of 106 taxa were identified. Of these, 85 were
      found in Balik lagoon and 78 were found in Uzun lagoon. Water temperature of the
      lagoons ranged from 6.5 to 24.5 degrees C during the sampling period.
      Conductivity hardness, dissolved oxygen an pH values varied between 0.70 and 8.00
      mS, 26.00 and 86.60 degrees f, 3.50 and 9.00 mg l(-1) and 7.82 and 8.70
      respectively. Nitrite nitrogen, nitrate nitrogen, chloride, phosphate phosphorus
      and sulphate concentrations in the water were also measured and ranged from 0.01
      to 0.14, 0.01 to 0.24, 2.41 to 48.70, 0.01 to 0.12 and 54.00 to 104.40 mg l(-1)
      respectively Species richness (d), diversity (Shannon - Weaver, H') and evennes
      (J') were calculated for epipelic algae and the findings showed similar
      oscillations throughout the research period. Cluster analyses and
      multidimensional scaling (MDS) revealed a similar distribution pattern of
      epipelic algal flora in both lagoons.

PMID- 20143706
TI  - Non-destructive leaf area measurement in maize (Zea mays L.).
AB  - In this research, leaf area prediction model was developed for some leaf-used
      maize (Zea mays L.) cultivars namely Coluna, Luce, Maveric, Ranchero, TTM-813,
      Zamora and RX-788 grown in Black Sea region of Turkey. Lamina width, length and
      leaf area were measured without destroying the leaf to develop the models. The
      actual leaf areas of the plants were measured by PLACOM Digital Planimeter and
      multiple regression analysis with Excel 2003 computer package program was
      performed for the plants separately. The produced leaf area prediction models in
      the present study were formulized as LA = a - (b x W2) + [c x (W x L)] where LA
      is leaf area, W is leaf width, L is leaf length and a, b, c are coefficiencies.
      R2 values for maize cultivars tested varied with species from 0.95 in Luce to
      0.98 in Maveric. All R2 values and standard errors were found to be significant
      at the p < 0.001 level.

PMID- 20143707
TI  - Studies on luminous, Vibrio harveyi associated with shrimp culture system rearing
      Penaeus monodon.
AB  - Microbiological studies in a modified extensive shrimp culture system at
      Nambuthalai, southeast coast of India were carried out fora period of 120 days.
      Population dynamics and distribution profile of luminous bacteria and total
      heterotrophic bacteria in the water sediment and animal samples were monitored.
      Luminous bacteria associated with exoskeleton, gills and gut were isolated and
      quantified. The total heterotrophic bacterial counts ranged from 1.3 x 10(4) to
      25.3 x 10(4) CFU ml(-1) in water and 1.5 x 10(6) to 26.2 x 10(6) CFU g(-1) in
      sediment. The V. harveyi population density varied between 0.6 x 10(4) and 8.8 x
      10(4) LCFU ml(-1) in water and from 1.2 x 10(6) to 10.4 x 10(6) LCFU g(-1)
      sediment respectively. The gut of the animal was found to harbor high density of
      V. harveyi than gills and exoskeleton. The total heterotrophic bacteria and V.
      harveyi population density showed increasing trend during the culture period. The
      high V harveyi density observed in this study at the end of the culture period
      correlated with the outbreak of white spot disease.

PMID- 20143708
TI  - Impact of combined exposure of chemical, fertilizer, bio-fertilizer and compost
      on growth, physiology and productivity of Brassica campestries in old alluvial
      soil.
AB  - Field experiment was carried out during November 2006 to February 2007 under old
      alluvial soil to evaluate the impact of combined dose of chemical fertilizer,
      biofertilizer in combination with compost for the yellow sarson (Brassica
      campestries cv. B9) in a randomized block design replicated thrice. Various
      morpho-physiological parameters viz., plant population, length of shoot and root,
      leaf area index (LAI), crop growth rate (CGR), net assimilation rate (NAR), yield
      attributes viz., number of siliquae per plant, number of seeds/siliquae, 1000
      seed weight (test weight), seed yield, stover yield and physiological and
      biochemical parameters viz., pigment content, sugar, amino acid, protein,
      ascorbic acid content in physiologically active leaf were performed. The
      treatment T1 i.e., 40% less N fertilizer 25% less P fertilizer K fertilizer
      constant + 12 kg ha(-1) biofertilizer (Azophos) and organic manure (compost) @
      5Mt ha(-1), showed the maximum chlorophyll accumulation (10. 231 mg g(-1)
      freshweight), highest seed/siliquae (25.143), test weight of seeds (4. 861g) and
      highest seed yield (10.661 tha(-1)). A comparison between all the morphological,
      anatomical, physiological and biochemical parameters due to application of
      chemical fertilizer; bio-fertilizer and compost alone and in combination and
      their impact on soil microorganism, flora and fauna will throw a sound
      environmental information.

PMID- 20143709
TI  - Seasonal and vertical distributions of porewater phosphorus and iron
      concentrations in a macrophyte-dominated eutrophic lake.
AB  - In this study variations in total dissolved phosphorus (TDP), soluble reactive
      phosphorus (SRP) and total iron (TFe) concentrations and pH values in the
      littoral sediment porewater of macrophyte-dominated eutrophic Mogan Lake
      (Turkey), were determined depth wise (0-20 cm, on a basis of 5 cm depths) over a
      period of eleven months. Additionally water temperature, dissolved oxygen, redox
      potential, TDP, SRP and TFe levels in the overlying water were measured.
      Especially in the spring and summer months constituting a large portion of the
      research period, seasonal variation of SRP at depths between 0-5 cm and 15-20 cm
      were not found to be statistically significant (p > 0.01). However in the fall
      and winter months, surface sediment (0-5 cm) SRP values were elevated in
      comparison with deeper sediment depths. As for TFe values, no clearseasonal
      variation was evident at different depths. Due to the fact that TFe
      concentrations in the overlying water (101.25-511.67 mg x m(-3)) were lower than
      iron concentrations in the porewater (104.00-783.00 mg x m(-3)), positive
      phosphorus release remained at low levels. In this eutrophic lake, in which
      action is continuing to reduce the external phosphorus load, monitoring SRP
      variations in the overlying water and porewater would be beneficial.

PMID- 20143710
TI  - Protective effect of lycopene against mercury-induced cytotoxicity in albino
      mice: pathological evaluation.
AB  - The present study was carried out to evaluate the protective role of lycopene on
      cytotoxicity induced by mercury in albino mice. The animals were randomly divided
      into seven groups. Group I (control) were treated with tap water Group II
      (positive control) were treated with 20 mg kg(-1) d(-1) lycopene, Group III were
      treated with 10 mg kg(-1) body weight mercury Group IV were treated with 10 mg
      kg(-1) body weight mercury + 5 mg kg(-1) d(-1) lycopene, Group V were treated
      with 10 mg kg(-1) body weight mercury + 10 mg kg(-1) d(-1) lycopene, Group VI
      were treated with 10 mg kg(-1) body weight mercury + 15 mg kg(-1) d(-1) lycopene,
      Group VII were treated with 10 mg kg(-1) body weight mercury + 20 mg kg(-1) d(-1)
      lycopene once a day for 20 consecutive days by oral gavage. The initial and final
      weights of all mice were measured by sensitive balance in order to investigate
      the effect of mercury and lycopene on the body weight of mice. Then, MN slides
      were prepared using the standard MN assay technique with Giemsa staining from
      erythrocyte cells of each mouse and were scored using binocular light microscope
      (Japan, Olympus BX 51). The results indicated that, all lycopene-supplemented
      lymphocytes showed a lower MN frequency than lymphocytes in only mercury-treated
      group. It was seen that lycopene had protective effect on MN particularly at 20
      mg kg(-1) d(-1) dose when compared with the other doses. Besides, weight gain
      increased depending on dose of applied lycopene when compared with only mercury
      treated group. In histopathological examinations, although it has been observed
      severe changes such as hemorrhage, hepatocyte degeneration and tubular
      degeneration of kidney in only mercury-treated group, there was an observable
      regression on the severity and account of these lesions in tissues of mice
      supplemented with different doses of lycopene. In vivo results showed that the
      lycopene supplementation decreases cytotoxicity induced by mercury and its
      protective role is dose-dependent.

PMID- 20143711
TI  - Soil respiration in apple orchards, poplar plantations and adjacent grasslands in
      Artvin, Turkey.
AB  - In this study influence of land-use type on soil respiration was investigated in
      poplar plantation, apple orchard (apple trees with understory grasses) and
      adjacent grassland sites in Seyitler Area, Artvin, Turkey. Soil respiration was
      measured approximately monthly in three sampling plots in each land use type from
      January 2005 to November 2005 using the soda-lime technique. Mean daily soil
      respiration ranged from 0.63-3.59 g Cm(-2) d(-1). Mean soil respiration in apple
      orchard, poplar plantation and grassland sites were 1.98, 1.45 and 1.12 g C m(-2)
      d(-1), respectively. Mean soil respiration was significantly greater in apple
      orchard than in poplar plantations and grasslands. Seasonal changes in soil
      respiration were related to soil moisture and temperature changes. Mean soil
      respiration rate correlated strongly with subsurface soil (15-35cm) pH (R = 
      0,73; p < 0.05), sand content (R = 0.96, p < 0.001), soil silt content (R = 
      0.75; p < 0.05), soil clay content (R = -0.83; p < 0.001) and organic matter
      content (R = 0.88; p < 0.001). No significant correlations were observed between
      soil respiration and surface (0-15 cm) soil properties and root biomass. Overall,
      our results indicate that apple orchards with understory grasses have higher soil
      biological activity compared to poplar and grassland sites.

PMID- 20143712
TI  - Accumulation of lead and copper in Rhizophora apiculata from Setiu mangrove
      forest, Terengganu, Malaysia.
AB  - The accumulative partitioning of Pb and Cu in the Rhizophora apiculata was
      studied randomly in the Setiu mangrove forest, Terengganu. Samples of leaves,
      barks and roots were collected randomly from the selected studied species.
      Sediments between the roots of the sampled mangrove plants were also collected.
      The results from analysis for Rhizophora apiculata shows that the concentration
      of Pb and Cu were accumulated higher in root tissue compared to bark and leaf
      tissue but lower than surrounding sediment level. The average concentration of Cu
      for Rhizophora apiculata in leaf, bark, root and sediment was 2.73, 3.94, 5.21
      and 9.42 mg I(-1), respectively. Meanwhile, the average concentration of Pb in
      leaf, bark, root and sediment was 1.43, 1.38, 2.05 and 11.66 mg l(-1),
      respectively. Results of concentration factors (CF) show that the overall the
      concentration of Pb and Cu were accumulated much higher in roots system of
      Rhizophora apiculata.

PMID- 20143713
TI  - The effects of land use change on soil properties and organic carbon at Dagdami
      river catchment in Turkey.
AB  - This research was carried out in Dagdami river catchment located in the highlands
      of the Black sea region of Turkey. The objective of this study was to investigate
      the effects of representative land-use and land-cover types of largely deforested
      areas of Black sea region on soil properties. We measured these effects by
      quantifying some soil analyses were done on soil samples were taken at two depths
      (0-5 and 5-15 cm) and two aspects (N and S). According to the results of
      statistical analysis, satured hydraulic conductivity (K(sat)), bulk density (BD),
      water stable aggregates (WSA), soil organic matter (SOM), soil organic carbon
      (SOC) and total nitrogen significantly change with land use type and aspect.
      Results have shown significantly higher values of saturated hydraulic
      conductivity (K(sat)) in natural forest top soil (82.4 cm3 x h(-1) on average)
      compared to grasslands soils (8.4 cm3 h(-1)) and hazelnut garden soils (11.5 cm3
      h(-1)) and corn field soils (30.0 cm3 x h(-1)). It was determined that WSA was
      greater in the pasture and forest soils than in cultivated soils. In addition,
      K(sat) was found the highest value in the forest soils at all aspects while, SOM
      and SOC of forest soils are higher than other land use types. On the other hand,
      amount of SOM and SOC of soils of grassland, hazelnut garden and corn field are
      low level and close to each other Soils under hazelnut garden (1.1 g cm(-3)) and
      grassland (1.1 g cm(-3)) have higher bulk density than the adjacent soils under
      forests (0.7 g cm(-3)) and corn field (1.0 g cm(-3)) for two different aspects.
      Furthermore, after long-term continuous cultivation of the natural forest soil,
      it was determined that some physical and chemical characteristics of it has been
      significantly changed.

PMID- 20143714
TI  - Biomonitoring of zinc and manganese in bark of Turkish red pine of Western
      Anatolia.
AB  - Turkish red pine (Pinus brutia) is a widespread evergreen tree in Mediterranean
      andAegean regions of Turkey. The barks of Pinus brutia were tested as a possible
      biomonitor of Zn and Mn accumulation studied in Western Anatolia, Turkey. Samples
      collected from industry roadside, suburban and rural areas from thirty locations
      in the study area were investigated. The concentration of zinc and manganese were
      determined in the bark of the red pine by atomic absorption spectrometry. As a
      result of this study the following mean concentrations were determined: for Zn
      between min 8.4 and max 14.1 microg g(-1), and for Mn between min 19.1 and max
      24.0 microg g(-1). It was found that there is no affect of location on the
      element concentration of both Mn and Zn.

PMID- 20143715
TI  - Microbial evaluation and deterioration of paints and paint-products.
AB  - The microbial quality of materials and final products of a reputable paint
      industry in Lagos area were analysed. The bacterial contaminants isolated in the
      paint-products included Bacillus brevis, B. polymyxa, B. laterosporus,
      Lactobacillus gasseri, L. brevis, Escherichia coli and Proteus mirabilis. The
      fungal contaminants detected in the paints were mainly Aspergillus niger, A.
      flavus and Penicillium citrinum. The microbial populations in the raw materials
      ranged from 1.0 x 10(6) - 9.5 x 10(6) cfu g(-1) for bacteria and between 1.25 x
      10(4) and 6.8 x 10(4) cfu g(-1) for fungi while those present in packaging
      materials ranged from 3.45 x 10(6) - 7.65 x 10(6) cfu g(-1) for bacteria and 2.4
      x 10(3) - 2.8 x 10(3) cfu g(-1) for fungi respectively. The bacterial populations
      in the fresh paint samples monitored every two weeks from the time of production
      ranged from 1.6 x 10(1) - 4.7 x 10(5) cfu ml(-1) while the fungal populations
      ranged from 1.0 x 10(1) - 5.5 x 10(3) cfu ml(-1) over a ten-month study period.
      The optical density at 600 nm increased while transmittance, pH, specific gravity
      and viscosity of the paint samples decreased over the period suggesting gradual
      deterioration of the aesthetic qualities of the paint-products with time as
      indicated by the measured parameters.

PMID- 20143716
TI  - Increased eutrophication and nutrient imbalances in the agricultural soil of NE
      Catalonia, Spain.
AB  - The soil C, N, P and K content of agricultural soil were measured over the last 4
      decades in NE Catalonia (NE Spain). Plant-available P and K increased by ca 109
      and 105% respectively and total N decreased by 30%. The increases in plant
      available P content are in accordance with the increasingly used pig slurry being
      very rich in P, and with P tendency to be retained in soils, since it is less
      mobile than N. The total soil N (N(tot)) decrease occurred in the first decade
      (by 41%). The uptake and withdrawal of mineral N by crops and the leaching of
      mineral N into groundwater and rivers after torrential rainfalls were the two
      likely major pathways of N-loss from the soil. After the first decade, there has
      been no further decrease of N(tot) as a result of the increasing fertilization of
      these fields, including the increasing applications of pig slurry. These results
      show an increasing P eutrophication in Mediterranean agricultural soils and will
      have several consequences for the next decades with (i) an increasing unbalance
      between N and P (and K) in soils that might affect crop productivity (ii) an
      increasing leaching of N as nitrate to continental waters, both ground and
      surface waters, and (iii) a consequent need for the establishment of another
      fertilization strategy based on lowering the use of pig slurry and on increasing
      the use of fertilizers of slow mineralization that increase soil organic matter,
      and stabilise the soil N and P contents.

PMID- 20143717
TI  - Lactic acid production from cassava fibrous residue using Lactobacillus plantarum
      MTCC 1407.
AB  - During extraction of starch from cassava, fibrous residue is a major waste
      released into the environment. Owing to the high starch content (60-65% on dry
      weight basis) and organic matter of cassava fibrous residue (CFR), an attempt has
      been made to utilize it for the production of lactic acid (LA) in semi solid
      state fermentation using Mann Rogassa Sharpe medium containing [5 % (wv(-1))] CFR
      in lieu of glucose [2% (wv(-1))] as the carbon source. Response Surface
      Methodology (RSM) was used to evaluate the effect of main variables, i.e.
      incubation period, temperature and pH on LA production. The experimental results
      showed that the optimum incubation period, temperature and pH were 120 hr 35
      degrees C and 6.5, respectively. Maximum starch conversion by Lactobacillus
      plantarum MTCC 1407 to LA was 63.3%. The organism produced 29.86 g of (L+) LA
      from 60 g of starch present in 100 g of CFR. The LA production yield (i.e. mass
      LA produced mass starch present in CFR(-1) x 100) was 49.76%.

PMID- 20143718
TI  - An ordination of the forest communities in Nainital catchment of Kumaun Himalaya.
AB  - Evergreen forest communities distributed within 1580-2600 m above sea level (asl)
      in Kumaun Himalaya were studied. Quercus leucotrichophora A. Campus, Q.
      floribunda Lindl. ex Rehder Q. semecarpifolia J.E. Smith and Pinus roxburghii
      Sarg. are the dominant tree species in banj-oak, tilonj-oak, kharsu-oak and chir
      pine forests, respectively. Total density for tree, shrub and herb layer varied
      from 3.7 to 10.5 (individual 100 m(-2)), 2.0 to 38.8 (individual 100 m(-2)) and
      5.5 to 44.0 (individual m(-2)), respectively. A total of five forests types (27
      stands) were identified in the field on the basis of species richness and species
      diversity by applying polar ordination method. The diversity value fortree, shrub
      and herb layer ranged from 0 to 3.62, 0.36 to 3.85 and 1.23 to 4.21,
      respectively. Present study indicates the spatial patterns of vegetation in
      different forest communities at different altitudes.

PMID- 20143719
TI  - Protective effects of selenium on fluoride induced alterations in certain enzymes
      in brain of mice.
AB  - This study reports the protective effects of selenium on fluoride induced
      alterations in the activities of pro-oxidative (xanthine oxidase (XOD), lipid
      peroxidation (LPO) free radical scavenging, [catalase, superoxide dismutase
      (SOD), glutathione-s-transferase (GST), glutathione peroxidase (GPX), glutathione
      reductase (GR), glutathione) and metabolic (glucose-6-phosphate dehydrogenase,
      alanine amino transferase (ALAT), aspartate aminotransferase (AAT), creatine
      phosphokinase (CPK), acid phosphatase (AP), alkaline phosphatase (ALP)] enzymes
      along with fluoride and selenium levels in brain of mice. Animals were divided
      into control, NaF treated group (20 mg kg(-1) body wt.(-1) intraperitonial) and
      Selenium+NaF treated group (sodium selenite, 5 microg of selenium/0.2 ml
      distilled water kg(-1) body wt.(-1) day) and were maintained for 14 days on
      respective treatments. The decreased bodyweight (-11.35%) as well as
      organosomatic index (-15.1%) of brain in NaF group were recovered in treatment of
      selenium along with NaF. The increased accumulation of fluoride (32.1%) in brain
      observed in NaF treated group compared to control was diminished in selenium+NaF
      treated group. Selenium levels (3.03%) increased in selenium+NaF treated group in
      compared to decrement in NaF treatment. The SOD (-16.6%), Catalase (-21.5%), GST(
      13.72%), GPX (-19.16%), GR (-44.97%) activities and Glutathione (-23%) content in
      NaF treated group were decreased significantly compared to controls, which were
      significantly (p < 0.01) recovered in selenium+NaF group. Increased XOD (10.85%)
      and LPO (8.61%) levels observed in brain of NaF treated mice were reversed with
      selenium treatment. Glucose-6-phosphate dehydrogenase (-46.98%), ALAT (-10.44%),
      AAT (-10.21%), CPK (-27.98%) were decreased and alkaline phosphatase (10.6%),
      acid phosphatase (24.09%) increased in brain of mice after administration of NaF.
      All metabolic enzymes were significantly (p < 0.01) reversed after administration
      of selenium to the NaF treated group. Thus, the adverse effects of NaF on
      oxidative and metabolic enzymes of brain were reversible with ameliorative action
      of selenium supplementation. As evident in this study the antioxidative nature of
      selenium coupled with its reversal effect on metabolic enzymes in brain of mice
      treated with fluoride suggests its use as antidote agent against fluorosis.

PMID- 20143720
TI  - Use of benthic biodiversity for assessing the impact of shrimp farming on
      environment.
AB  - An attempt was made to find out the impact of shrimp farm discharges on benthic
      diversity in the discharge point of a shrimp farm. The duration of the study was
      one culture period right from stocking to harvest. The results revealed that the
      values of environmental entities were in the safe levels. As regards nutrients,
      maximum value of TOC and phosphorus were recorded in the sample collected after
      harvest and minimum in the sample collected during culture. BIO-ENV method
      revealed that nitrogen, sediment salinity and TOC were manifested as best
      variable combination explaining faunal distribution. Polychaetes are the dominant
      group (50%) with 13 species followed by crustaceans (32%) with 10 species,
      gastropods (10%) with 2 species and bivalves (8%) with 3 species. The faunal
      density was found to vary in relation to months as observed in the samples which
      were collected during various seasons in the other areas of estuary. In line with
      this, diversity values were also paralleled to the faunal density. In a nut
      shell, the study revealed no negative impact of shrimp farming to the estuarine
      benthic biota.

PMID- 20143721
TI  - Responses of cyanobacterium Anabaena doliolum during nickel stress.
AB  - Growth and biochemical responses of heterocystous nitrogen fixing cyanobacteria
      Anabaena doliolum were studied upon exposure to various concentrations of nickel
      (0.1 to 100 microM) for duration of up to 4 days, in view of its tolerance. The
      growth of the cyanobacterium was increased in terms of cell density (O.D),
      heterocyst frequency chlorophyll-a, carotenoid and c-phycocynin up to moderate
      exposure (10 microM for 96 hr of Ni treatment). Protein and total non protein
      thiol were measured as stress responsive metabolites and frequency of heterocyst
      and spores were observed in responses to Ni. The present study demonstrated that
      the tested cyanobacterium exhibited dose specific responses of metal towards
      studied different morphological, physiological and biochemical parameters.

PMID- 20143722
TI  - Optimization of Xhhh strain biodegradation with metal ions for pharmaceautical
      wastewater treatment.
AB  - Effects of three ions, Mn2+, Cu2+ and Zn2+ on biological treatment of
      pharmaceutical wastewaterby a functional strain Xhhh were investigated. Through
      orthogonal tests, Cu2+ was determined to be the most important factor influencing
      Xhhh biodegradation performance. Biodegradation kinetic experiments demonstrated
      that with Cu+ concentration at about 200 mg l(-1), the maximum of specific growth
      rate and specific degradation rate were obtained to be 0.033 and 0.075 d(-1),
      respectively. The optimal levels of Mn2+ (5.00 mg I(-1)), Cu2+ (2.00 mg l(-1))
      and Zn2+ (5.00 mg l(-1)) were achieved based on experimental results of their
      effects on the activities of manganese peroxidase and lignin peroxidase, and
      biodegradation kinetic parameters. Among three types of biodegradation kinetic
      models (Monod, Tessier and Contois), Tessier model was found most reasonable for
      kinetics description of Xhhh growth (R2 = 0.995) and pollutants degradation (R2 =
      0.970) in the case of metals optimization. Both kinetics evaluation and
      experimental results demonstrated that optimization with the three metals made a
      great contribution to Xhhh growth and COD removal for pharmaceutical wastewater
      treatment.

PMID- 20143723
TI  - Evaluation of larvicidal efficacy of Solanum xanthocarpum storage against vector
      mosquitoes in north - western Rajasthan.
AB  - Efficacy of the methanol extracts from fruits without seeds, whole yellow ripe
      fruits and seeds of the plant Solanum xanthocarpum was evaluated against larvae
      of Anopheles culicifacies, Anopheles stephensi, Aedes aegypti and Culex
      quinquefasciatus, the important vector mosquitoes prevalent in the arid region.
      Experiments were carried out on late 3rd or early 4th instar larvae of these
      mosquitoes using standard WHO technique. 24 and 48 hr LC50 and LC90 values along
      with their fiducial limits, regression equation, chi-square (chi2)/heterogeneity
      of the response have been determined by log probit regression analysis. The 24 hr
      LC50 values as observed for fruit without seeds, whole fruits and seeds after six
      months were 79.6, 91.7 and 131.7; 131.4, 186.9 and 195.6; 273.4, 290.9 and 377.6
      and 384.9, 450.6 and 520.0 mg l(-1) for An. culicifacies, An. stephensi, Ae.
      aegypti and Cx. quinquefasciatus respectively. However, the 24 hr LC50 values for
      fresh yellow ripe fruits and seeds determined previously were 51.6 and 66.9; 52.2
      and 73.7; 118.3 and 123.8 and 157.1 and 154.9 mg l(-1) for the above four vector
      species respectively showing that the efficacy was decreased two to three times
      more after six months of storage. The 24 hr LC50 values were also determined
      after one year of storage for fruit without seeds, whole fruits and seeds. The
      values were 103.3, 120.1 and 195.7; 146.3, 224.3 and 251.2; 316.9, 336.5 and
      426.2 and 393.0, 500.3 and 656.7 mg l(-1) as compared to the 24 hr LC50 values of
      47.4, 51.6 and 66.9; 52.3, 52.2 and 73.7; 108.0, 118.3 and 123.8 and 141.1, 157.1
      and 154.9 mg l(-1) of all the three fresh preparations for the above four vector
      species respectively showing that the efficacy was further decreased after one
      year of storage. Further the extracts should be used when they have been prepared
      from the fresh plant parts instead of the old stored parts. Larvae of anophelines
      were found more susceptible as compared to culicine. HPLC and IR studies showed
      that active component might be present in the fruits and seeds of this plant
      species. The study would be of great importance while planning vector control
      strategy based on alternative plant derived insecticides.

PMID- 20143724
TI  - A study of physico-chemical characteristics of lakes around Jaipur, India.
AB  - Annual survey of Jalmahal, Amer, Nevta and Ramgarh lakes, has been conducted for
      one calendar year, to determine physicochemical characteristics of water and the
      levels of zinc (heavy metal) and endosulfan (an organochlorine pesticide). These
      lakes are situated on the outskirts of Jaipur city. Changes in pollutants
      correlated well with the physico-chemical characteristics of water bodies.
      Results reveal that the levels of endosulfan and zinc are highest in Jalmahal
      lake (1.324 and 0.197 mg l(-1) respectively) and lowest in Ramgarh lake (0.020
      and 0.120 mg l(-1) respectively). Anthropogenic sources and cultivation in the
      dried up area of these lakes seem to contribute largely to pollution.

PMID- 20143725
TI  - Effect of cadmium on lactate dehyrogenase isoenzyme, succinate dehydrogenase and
      Na(+)-K(+)-ATPase in liver tissue of rat.
AB  - Cadmium is known to be an environmental and industrial pollutant. Exposure to
      cadmium is known to affect various tissues. The purpose of this study is to
      determine the toxic effects of cadmium on lactate dehydrogenase (LDH) isoenzymes.
      Administration of cadmium chloride (3 mg kg(-1)) resulted in the reduction of
      LDH4 fraction of liver tissue indicating the inhibitory effect of cadmium. The
      LDH1 LDH3 and LDH5 fractions showed decreasing trend initially but there was a
      significant increase later In contrast the LDH2 fraction showed increasing trend
      after 24 hr from the last dosage it was elevated after 30 days. The total
      activity of LDH in liver showed gradual reduction in both groups. The activity of
      succinate dehydrogenase (SDH) the mitochondrial enzyme has been observed to be
      inhibited by cadmium with the possibility of interfering with energy transport
      mechanism. Na(+)- K(+)-ATPase activity of liver also showed similar decrease
      after cadmium administration which may lead to general deficit in cell membrane
      transport. As cadmium shows drastic decrease in all the enzymes studied, the LDH2
      fraction which sharply rises from the control may be used as a marker enzyme to
      asses the liver injury.

PMID- 20143726
TI  - A preliminary study on the anti-inflammatory activity of methanol extract of Ulva
      lactuca in rat.
AB  - Anti-inflammatory drugs presently available for the treatment of various
      inflammatory disorders have diverse and undesirable side effects. In recent
      years; active principles of varied chemical structures have been isolated from
      plants possessing anti-inflammatory activity. Sulfated polysaccharides present in
      algae were shown to posses anti-inflammatory properties. Ulva lactuca the green
      alga available in Tuticorin coast was found to show anti-inflammatory effect as
      evidenced by the reduction in the inhibition of oedema at the 4th day of the
      experiment compared with the positive control drug and control. Microscopic
      examination of the elite organs did not show any alteration compared with the
      control and reference group. Moreover the hematological parameters were found
      normal compared with the control. The present study suggests the need for further
      studies for the development of anti-inflammatory drug of marine origin with
      proper clinical trials.

PMID- 20143727
TI  - Work zone noise levels at Aarti steel plant, Orissa and its attenuation in far
      field.
AB  - The outdoor noise levels from the various work places of the integrated steel
      plant were measured. The average noise level (L(eqst)) at the outdoor was found
      between 59-84 dBA. The combined noise level (L(eq)) of the plant was 90 dBA and
      92 dBA on 1.12.2006 and 1612.2006, respectively. The noise levels in the far
      fields were found between 43-70 dBA for daytime and meet the noise quality for
      industrial (75 dBA) area and residential (55 dBA) areas. Maximum attenuation of
      47-49 dBA of noise level was found at worker's colony and may be attributed
      mainly to the ground absorption. As the air quality standards of the area in
      respect of noise in the ambient is tending to increase, engineering control
      measures suggested to the noisiest equipments for better economically viable and
      higher payback period.

PMID- 20143728
TI  - Water quality and conservation management of Ramsagar reservoir, Datia, Madhya
      Pradesh.
AB  - The aim of this study is to assess physico-chemical characteristics, trophic
      status, pollution studies and macrophytic community of Ramsagar reservoir from
      April 2003 to March 2005. The range of various parameters of reservoir water
      (water temperature 15.92-31.87 degrees C, water depth 2.90-8.25 m, transparency
      66.59-116.00 cm, electrical conductivity 108-246.30 microS cm(-1), turbidity 2.17
      16.72 NTU, total dissolved solids 166.37-239.00 mg l(-1), pH 7 41-8.95, dissolved
      oxygen 6.78-11.59 mg I(-1), free carbon dioxide nil-6.32 mg l(-1), total
      alkalinity 64.25-146.25 mg l(-1), total hardness 34.00-75.25 mg l(-1), chlorides
      13.13-22.36 mg l(-1), calcium 11.21-33.81 mg l(-1), sulphates 1.50-8.87 mg l(-1),
      nitrates 0.011-0.033 mg l(-1), nitrites 0.004-0.029 mg l(-1), phosphates 0.013
      0.054 mg l(-1), silicates 0.65-8.42 mg l(-1), ammonia nil-0.84 mg l(-1),
      biochemical oxygen demand 0.93-4.68 mg l(-1), chemical oxygen demand 3.60-17.40
      mg l(-1), magnesium 1.17-5.60 mg l(-1), sodium 16.75-34.30 mg l(-1) and potassium
      1.97-4.86 mg l(-1)) exhibit monthly as well as seasonal fluctuations. The
      nutrients including silicates, sulphates, phosphates, nitrates and potassium are
      in sufficient quantities for the growth of aquatic plants and animals in the
      reservoir. In all 13 species of macrophytes were recorded from the reservoir.
      Macrophytic diversity was higher at the points where nallahas join the reservoir
      and in the areas where agricultural practices are performed. This was due to
      allocthonous nutrients brought into the reservoir from the surrounding catchments
      area. The above study indicated that the Ramsagar reservoir is under the category
      of mesotrophic water body slightly inclined towards eutrophication. Therefore,
      the conservation and management of this water body are very much required.

PMID- 20143729
TI  - Responses of parathyroid gland, C cells, and plasma calcium and inorganic
      phosphate levels in rat to sub-lethal heroin administration.
AB  - In order to record the effects of heroin on plasma calcium (Ca) and inorganic
      phosphate (Pi) levels as well as parathyroid gland and C cells, two sub-lethal
      doses (0.50 LD50 and 0.75 LD50) of the drug were administered intramuscularly in
      Rattus norvegicus for 30 days. Plasma Ca level of control rats ranged between
      9.53 +/- 0.32 - 9.88 +/- 0.22 mg 100 ml(-1) while plasma Pi concentration
      fluctuated between 4.55 +/- 0.18 - 4.71 +/- 0.24 mg 100 ml(-1). Sub-lethal heroin
      administration induced progressive increase in plasma Ca level during the first
      seven days (p < 0.001), thereafter the level declined on day 15 and 30. However
      plasma Pi level of the heroin-treated rats registered increase with the peak
      value (p < 0.001) on day 30. The treatment elicited degenerative changes in
      parathyroid gland as evident by cytoplamic vacuolization, presence of more
      pycnotic nuclei and occurrence of patchy areas among the chief cells.
      Degenerative changes were also noticed in cristae of mitochondria, Golgi complex
      and endoplasmic reticulum. There was decrease in chromatin material in the
      nucleus and loss of hormone granules in the cytoplasm. Oxyphil cells of the
      heroin-treated rat depicted dilation of endoplasmic reticulum and damaged
      cristae. Sub-lethal heroin administration in the rat for 30 days induced dilation
      in endoplasmic reticulum and loss of secretory granules in C cells.

PMID- 20143730
TI  - Inhibition and recovery of cholinesterases in Odontophrynus americanus tadpoles
      exposed to fenitrothion.
AB  - We determined the levels of brain acetylcholinesterase (AChE) and tail
      butyrylcholinesterase (BChE) activities in tadpoles of Odontophrynus americanus
      exposed to a commercial formulation of fenitrothion. The mean brain AChE
      activities in the controls tadpoles varied from 6.91 to 6.39 micromol min(-1) mg(
      1) protein, whereas tail BChE activities ranged among 0.26 to 0.17 micromol min(
      1) mg(-1) protein; the two sublethal concentrations of fenitrothion assayed
      produced AChE and BChE inhibition (p < 0.01). Brain AChE recovered a substantial
      level of activity with a maximum of 93.2%; after the transference of tadpoles to
      a free-pesticide solution, whereas tail BChE recovery showed a smaller increase
      (39%) in the activity at 168 hr after to transference to clear water. According
      with our results, we suggest that tadpole's tail BChE presents higher sensibility
      than brain AChE.

PMID- 20143732
TI  - [Research in nursing].

PMID- 20143731
TI  - Assessment of haematotoxic potential of mercuric chloride in rat.
AB  - The blood is an important liquid connective tissue flow in body and performs the
      role of distribution of oxygen to various tissues, taken out carbon dioxide and
      maintains the health status of an organism. Any change in the blood components
      can cause adverse effects on the body. The effect of mercuric chloride has been
      evaluated on blood in albino rats (Rattus norvegicus). The albino rats were
      treated with mercuric chloride 0.926 mg kg(-1) body wt. for acute (1 day) and
      0.044 mg kg(-1) body wt. for sub-acute (7, 14 and 21 day) sets after calculating
      LD50 (9.26 mg kg(-1) body wt.). Major changes have been observed in the form of
      enhanced clotting time (CT) and bleeding time (BT) due to toxic effect of
      mercuric chloride on haemopoietic system along with decrease in the total
      erythrocyte count (TEC) and haemoglobin concentration (Hb. conc.). The changes in
      erythrocyte count and haemoglobin concentration have been correlated with
      cytotoxic effect of mercuric chloride on erythropoiesis. However, the
      intoxication of mercuric chloride on total leukocyte count (TLC) and erythrocyte
      sedimentation rate (ESR) has been observed to be significantly increased after
      acute and sub-acute treatments due to leucocytosis and rouleux formation.
      Moreover the present observations highlight dose dependent toxicity.

PMID- 20143733
TI  - [Post operatory blood recuperators; bibliographical review].
AB  - The authors presented this report at the Apheresis Workshop at the Mexican
      Congress on Transfusions. VI Annual Congress AMMTAC in Monterrey, Nuevo Leon
      district. The use of post operatory recuperators, especially in orthopedic
      surgery is a habitual practice nowadays. Nurses play a special role in their
      handling and use; therefore, the authors comment on the reasons why these devices
      should be used. The authors also state different scientific evidence, based on a
      bibliographical review regarding the effectiveness of these systems, their
      utility, their product quality, their cost benefit, and the absence of
      undesirable effects. The authors conclude that there is a determined patient
      profile for when a patient benefits from the use of these devices. After some
      years of high use, at present times, there has been a reduction in using these
      devices due to, firstly the pre-surgical use of hematin agents, and secondly due
      to the development of certain less invasive surgical techniques. In spite of
      this, this procedure has proven to be cost effective. Nurses have an important
      role in the handling and use of these instruments which, combined with other
      measures such as the use of hemoglobin analysis devices at the head of a
      patient's bed, can contribute to an improved management of transfusion
      requirements.

PMID- 20143734
TI  - [Betadine as the preferred antiseptic in the protocol for minor surgery in
      primary health care].
AB  - Report awarded first prize in the Fourth Officially Announced Contest for the
      Betadine Prizes in 2009. This report details the operating protocol for the
      Health Center Salud II in the Ensanche neighborhood in Pamplona where the
      antiseptic preferred for use is this product.

PMID- 20143735
TI  - [Ethics in nursing research and investigation].
AB  - Investigation is indispensable for the nursing profession because it contributes
      to the development of the overall set of knowledge the profession has and thereby
      improves the practical, clinical care given to patients. However if we look into
      the history of research and investigation, we realize that investigators have not
      always respected persons' fundamental rights. This article starts with a short
      introduction which highlights the role played by investigation for the nursing
      profession. Then the author presents a historical overview on investigation in
      order to provide insights into the ethical problems related to investigation, and
      finally the author comments on the main ethical criteria which should be followed
      during investigation by nurses.

PMID- 20143736
TI  - [V.A.C. therapy application on perineum wound after a Miles operation or Miles
      resection].
AB  - Report rewarded with the VA.C. 2009 Therapy First Prize, as part of its third
      officially announced contest, in the discipline of best clinical case. This
      operation was carried out on a young woman who suffered from obesity (BMI:39) and
      who had been diagnosed by means of rectoscopy for colorectal carcinoma.

PMID- 20143737
TI  - [Co-morbility during depression].
AB  - Up to present times, more studies in medicine have been made on the effects an
      organic disease can cause in the brain as manifested by depression but, among
      different health disciplines, researchers are carrying out studies on how the
      brain can affect the body and cause diseases. By reviewing various
      epidemiological studies, relationships among some chronic diseases and depression
      have been noted. The depression-disease order of appearance can de bi
      directional. It seems that stress, depression and inflammation have the capacity
      to affect the balance of cykotines produced by the immunological system.
      Modulation of the immunological system by the central nervous system is
      controIled/mediada by a complex bi-directional network composed of signals among
      the central nervous system, the endocrine system and the immunological system.
      The most frequent diseases related to depression are chronic but some are acute:
      of the central nervous system, endocrines, infections. Chronic pain also seems
      related to this problem. Pain, fatigue or tiredness are considered symptoms of a
      hidden depression and others, physical as well as psychiatric, could be algias,
      parestesias, headaches, vertigo, or gastrointestinal, cardio-respiratory
      neurodegenerative disorders.

PMID- 20143738
TI  - [Abdominal cure procedures. Adequate use of Nobecutan Spray].
AB  - Open abdominal wounds, complicated by infection and/or risk of eventration tend
      to become chronic and usually require frequent prolonged cure. Habitual changing
      of bandages develop into one of the clearest risk factors leading to the
      deterioration of perilesional cutaneous integrity. This brings with it new
      complications which draw out the evolution of the process, provoking an important
      deterioration in quality of life for the person who suffers this and a
      considerable increase in health costs. What is needed is a product and a
      procedure which control the risk of irritation, which protect the skin, which
      favor a patient's comfort and which shorten treatment requirements while lowering
      health care expenses. This report invites medical personnel to think seriously
      about the scientific rationale, and treatment practice, as to why and how to
      apply Nobecutan adequately, this reports concludes stating the benefits in the
      adequate use of this product. The objective of this report is to guarantee the
      adequate use of this product in treatment of complicated abdominal wounds. This
      product responds to the needs which are present in these clinical cases favoring
      skin care apt isolation and protection, while at the same time, facilitating the
      placement and stability of dressings and bandages used to cure wounds. In order
      for this to happen, the correct use of this product is essential; medical
      personnel must pay attention to precautions and recommendations for proper
      application. The author's experiences in habitual handling of this product during
      various years, included in the procedures for standardized cures for these
      wounds, corroborates its usefulness; the author considers use of this product to
      be highly effective while being simple to apply; furthermore, one succeeds in
      providing quality care and optimizes resources employed.

PMID- 20143739
TI  - [Neurologically critical patient. Nurses' care].
AB  - Handling a neurologically critical patient requires some necessary knowledge and
      aptitudes in order to avoid risks and complications which could worsen a
      patient's prognosis. To that end, in this article the author deals with two
      important points nursing personnel need to bear in mind: the distinct methods and
      catheters which can be used to monitor intracranial pressure, obtaining an
      important parameter for evaluation purposes and therapeutic follow-up on these
      patients, placing special emphasis on ventricular drainage and nursing care, and
      the operations nurses take when dealing with patients who present a risk of
      intracranial hypertension, setting up a protocol based on seven necessities in
      the Virginia Henderson model: breathing, elimination, temperature, hygiene and
      skin, feeding and hydration, mobility and safety. In each of these necessities,
      the author studies the problems these patients present, identifying them with a
      series of diagnoses according to NANDA (North American Nursing Diagnosis
      Association), and defining the care or nursing activities for each of them, which
      will prove essential to prevent cerebral ischemia after suffering a primary
      cerebral injury due to a "TCE"(Cranial Encephalic Trauma) hemorrhage, etc.
      Nurses' role in caring for neurologically critical patients proves to be of vital
      importance since these professionals must be capable of evaluating, preventing,
      controlling and identifying those risk situations which neurologically critical
      patients could present, avoiding possible complications, aiding their
      recuperation, and providing quality health care.

PMID- 20143740
TI  - [Attitude towards immigration a study among nursing professionals].
AB  - Somewhat more than 5 million foreigners reside in Spain; they make up 11.3% of
      the total population, their presence implies an increase in the cultural
      diversity of the people who make use of public health services. By means of a
      descriptive quantitative study which used interviews, we have been able to
      discover the attitudes towards immigration which nursing professionals in the
      three public hospitals in the province of Almeria hold; and to analyze whether or
      not significant differences exist among them. After analyzing the results of more
      than 200 questionnaires collected, we can conclude that there are few clearly
      positive or negative attitudes while almost 75% of this sample show moderate
      attitudes and there are no statistically significant differences based on work
      place; therefore, we can suppose that the percentage of foreigners attended to
      does not determine the attitude toward immigration by personnel in each hospital.
      This research project was financed by the Andalucian Government's Health Council
      as part of those Biomedical and Health Sciences Research Projects subsidized in
      Andalucia in 2007, according to the official Andalucian Government publication
      "BOJA no 149 de fecha 30 de julio. Expediente: Pl 424-2007".

PMID- 20143741
TI  - [Nutrition needs of the patient with pressure ulcer].

PMID- 20143742
TI  - [Case of the month. Acute generalized exanthematous pustulosis due to an
      iodinated contrast radiodiagnostic agent].
AB  - Iodinated contrast agents are frequently involved in delayed polymorphic adverse
      skin reactions. Acute generalized exanthematous pustulosis following
      administration of iodinated contrast agents is a rare but severe form of such
      reactions. The disease is characterized by the sudden occurrence of an erosive
      and pustular erythroderma with fever, leukocytosis and sometimes peripheral
      adenopathies and liver involvement. This condition is considered as an
      immunologic reaction, primarily involving T lymphocytes. The overall mortality
      reaches about 1%. Elucidating the differential diagnosis with other acute
      paroxysmal drug eruptions (toxic epidermal necrolysis, Steven-Johnson syndrome
      and drug hypersensitivity syndrome) is of paramount importance for establishing
      the adequate treatment of PEAG.

PMID- 20143743
TI  - [Ezetimibe (Ezetrol) in patients with diabetes].
AB  - Ezetimibe (Ezetrol) selectively inhibits the intestinal absorption of cholesterol
      and phytosterols. Its mechanism of action results in a synergistic cholesterol
      lowering effect together with a statin that inhibits cholesterol synthesis by the
      liver, which leads to the development of a fixed ezetimibe-simvastatin
      combination (Inegy). Ezetimibe has been more particularly studied in patients
      with type 2 diabetes whose high cardiovascular risk is well known. The present
      article aims at describing recent advances and specificities concerning the use
      of ezetimibe in the diabetic population.

PMID- 20143744
TI  - [A FRAX model for the assessment of fracture probability in Belgium].
AB  - The objective of this study was to evaluate a Belgian version of the WHO fracture
      risk assessment (FRAX) tool to compute 10-year probabilities of osteoporotic
      fracture in men and women. A particular aim was to determine fracture
      probabilities that corresponded to the reimbursement policy for the management of
      osteoporosis in Belgium and the clinical scenarios that gave equivalent fracture
      probabilities. Fracture probabilities were computed from published data on the
      fracture and death hazards in Belgium. Probabilities took account of age, sex,
      the presence of clinical risk factors and femoral neck BMD. Fracture
      probabilities were determined that were equivalent to intervention
      (reimbursement) thresholds currently used in Belgium. Fracture probability
      increased with age, lower BMI, decreasing BMD T-Score, and all clinical risk
      factors used alone or combined. The FRAX tool has been used to identify possible
      thresholds for therapeutic intervention in Belgium, based on equivalence of risk
      with current guidelines. The FRAX model supports a shift from the current DXA
      based intervention strategy, towards a strategy based on fracture probability of
      a major osteoporotic fracture that in turn may improve identification of patients
      at increased fracture risk. The approach will need to be supported by health
      economic analyses.

PMID- 20143745
TI  - [Treatment of severe preeclampsia: until when and for what risks/benefits?].
AB  - The four major hypertensive disorders related to pregnancy are preeclampsia,
      chronic hypertension, preeclampsia superimposed upon chronic hypertension, and
      gestational hypertension. The development of hypertension and proteinuria in
      pregnancy is usually due to preeclampsia, particularly in a primigravida. These
      findings typically become apparent in the latter part of the third trimester and
      progress until delivery, but some women develop symptoms in the latter half of
      the second trimester, or intrapartum, or the early postpartum period.
      Preeclampsia is characterized as mild or severe. Severe hypertension,
      coagulopathy, thrombocytopenia, liver function abnormalities, and fetal growth
      restriction are features of severe disease. Laboratory evaluation should assess
      haemoglobin/hematocrit and platelet count, renal and hepatic function, as well as
      assessment of fetal well-being and growth. Timing of delivery is based upon
      gestational age, maternal and fetal condition, and the severity of preeclampsia.
      Maternal end organ dysfunction and nonreassuring tests of fetal well-being are
      indications for delivery at any gestational age. Antihypertensive treatment aims
      at protecting the mother from severe hypertensive encephalopathy, but may
      jeopardize the fetus. We recommend antenatal corticosteroids (betamethasone) be
      given to women with preeclampsia at 26 to 34 weeks of gestation. Magnesium
      sulfate is more effective than phenytoin for prevention of eclamptic seizures.

PMID- 20143746
TI  - [Pseudoxanthoma elasticum beyond skin, eyes and vessels].
AB  - The main clinical manifestations of pseudoxanthoma elasticum (PXE) alter small
      arteries, the eyes and the skin. At the microanatomical level, the feature in
      common is an alteration of the elastic fibres that appear dystrophic and in part
      calcified. The disease is genetically transmitted as an autosomal recessive
      trait. The gene coding for the MRP6 protein is often mutated. Thus PXE appears as
      a metabolic disease conveyed by serum.

PMID- 20143747
TI  - [Pseudoxanthoma elasticum: a study of 22 cases].
AB  - Pseudoxanthoma elasticum is a heritable connective-tissue disorder affecting the
      eye, skin, and vascular system. The aim of our study was to specify the
      epidemiological and clinical characteristics of this disease in a hospital
      series. A total of 22 patients were included during a period of 19 years. There
      were 15 women and 7 men. Patient's mean age was of 36,1 years. Parental
      inbreeding was reported in 10 cases. However, the parents were apparently healty.
      All patients exhibited cutaneous signs. The association between pseudoxanthoma
      elasticum and elastosis perforans serpiginosa was reported in two cases. The
      histological features were characteristic in all cases. The ophthalmologic
      examination realized on 13 patients revealed angioid streaks in 6 cases and a
      orange peel aspect in one case. Cardiac evaluation performed in 11 patients did
      not reveal specific PXE abnormalities. A follow-up was recommended in the
      majority of the cases. In conclusion, a family history of PXE was frequently
      reported in our study mainly among brothers and sisters. The disease was probably
      of autosomal recessive transmission. Cutaneous lesions were often the first
      signs. A list of laboratory investigations is useful to search for asymptomatic
      visceral localizations and specify their frequency.

PMID- 20143748
TI  - [Desmoid tumors of the abdominal wall: three cases].
AB  - Desmoids tumors are rare. They often develop from the fascia and muscles of the
      abdominal wall. They are considered as benign, but endowed with local
      aggressiveness. Treatment is primarily surgical. Complete resection with large
      safety margins and sometimes complex reconstruction is necessary to reduce the
      risk of local reccurrence. WE report three cases of histology proven desmoids
      tumors of the abdominal wall treated between 2000 and 2007. Etiologic factors,
      diagnosis, surgical management and adjuvant therapy in case of incomplete
      resection or reccurrence are discussed.

PMID- 20143749
TI  - [Regional analgesia after lower limb orthopaedic surgery].
AB  - To provide postoperative analgesia, the anaesthesist has at his disposal a panel
      of different medications and also regional techniques of neural blockade. Loco
      Regional analgesia (epidural or peripheral nerve block), by the use of local
      anaesthetics, blocks conduction of the painful influx to th central nervous
      system. Pain relief using peripheral nerve blocks after lower limb surgery
      represents as good alternative to the epidural analgesia and is superior to
      controlled analgesia with morphine. Peripheral nerve blocks, by decreasing the
      use of opioids in the postoperative period, reduce the incidence of side effects
      related to these molecules. They are also devoided of the adverse events due to
      the epidural analgesia like urinary retention or need for continuous monitoring.
      Analgesia after total knee prosthesis and hallux valgus surgery has considerably
      evolved. Postoperative analgesia is important in these cases: it facilitates
      physical therapy and improves patient's rehabilitation and satisfaction, it also
      shortens hospital stay. The aim of this review is to explain the different
      techniques of peripheral neural blockade and assess the value of this technique
      for the postoperative period after these two surgeries.

PMID- 20143750
TI  - [Antimicrobial peptide in dentisty. Literature review].
AB  - The use of antimicrobial substances has contributed to the development of
      multiple antimicrobial resistances (1), challenging the pharmaceutical industry
      to develop with new, innovative, and effective molecules. Discovered around 1980,
      molecules called natural antimicrobial peptides (AMPs) appear to hold great
      potential for the treatment of infections. These cationic peptides are able to
      stop the bacterial development and to control infections. The purpose of this
      review is to help improve the understanding of the way AMPs operate in the
      context of the development of new cures against viruses, bacteria, and mushrooms
      found in the human body in general and in the oral cavity in particular.

PMID- 20143751
TI  - [Management of an obese person with metabolic syndrome].
AB  - The management of an obese person requires a careful evaluation first, a
      multidisciplinary approach and a stepwise therapeutic strategy. The latter should
      favour lifestyle modifications, eventually the use pharmacological agents in good
      responders, and reserve bariatric surgery to well selected cases, refractory to
      medical treatment. Continuous motivational reinforcement is crucial for long-term
      success. In obese individuals at high metabolic risk, such strategy should aim at
      reducing the incidence of new-onset type 2 diabetes.

PMID- 20143752
TI  - Depressive symptoms in community-dwelling elderly Korean immigrants and elderly
      Koreans: cross-cultural comparison.
AB  - Depression among minority older adults is a prevalent underrecognized medical
      illness. Changes in cultural norms and social conditions because of immigration
      have a significant influence on mental health. The purpose of this study was to
      assess the interrelationships between acculturation, geographical location,
      gender, and depressive symptoms in community-dwelling elderly Korean immigrants
      and elderly Koreans. In this cross-sectional study, a convenience sample of 88
      elderly Korean immigrants and 295 elderly Koreans was recruited separately from
      senior centers and senior apartments. Depressive symptoms were assessed with the
      Korean Geriatric Depression Scale-Short Form and acculturation with years of
      living in the United States. Acculturation had no significant relationship with
      depressive symptoms (r = 0.01, p = 0.94). Depressive symptoms were highly present
      in both elderly Korean immigrants and elderly Koreans. The prevalence of
      depressive symptoms was higher in women. This study provides baseline data for
      development of culturally specific, community-based intervention programs for
      better management of mental health of elderly Korean immigrants.

PMID- 20143753
TI  - Compelling teaching with the four Cs: caring, comedy, creativity, and
      challenging.
AB  - The traditional classroom, particularly in nursing, often is stifling to students
      and teachers. A dynamic co-learning experience creates a potential to move
      students from merely obtaining knowledge to practice. This article presents an
      exemplar of the transformative learning process within the nursing education
      setting. The concepts forming this compelling teaching approach are caring,
      comedy, creativity, and challenging (the four Cs). Through this innovative
      teaching method, opportunities are created for authentic co-learning to occur.

PMID- 20143754
TI  - Digital stories: incorporating narrative pedagogy.
AB  - An ever-increasingly complex health care environment requires practitioners who
      can solve clinical problems from a range of perspectives and synthesize multiple
      sources of knowledge. Narrative pedagogy was the framework for a digital story
      assignment for a senior-level synthesis and clinical decision making course. This
      article describes how the use of digital stories enhanced students' clinical
      thinking strategies from a narrative pedagogy perspective.

PMID- 20143755
TI  - Constructivism in cultural competence education.
AB  - A graduate course on cultural diversity, based in constructivist theory and
      structured on the Process of Cultural Competence in the Delivery of Healthcare
      Services model, was developed and taught through classroom and online methods.
      The following research questions were explored: 1) Can an educational experience,
      built on constructivist learning theory tenets, change students' perceptions,
      attitudes, knowledge, and skills in the area of cultural competence? 2) Does the
      delivery method, online or traditional classroom, influence the degree of change?
      The study used a quasi-experimental, pretest-posttest control group design using
      the Inventory for Assessing the Process of Cultural Competence Among healthcare
      Professionals Revised. Findings showed significant changes (p<0.001) in cultural
      competence scores and subscores for all learners with both teaching modalities
      based on interval scale and in categories of cultural knowledge, skills, desire,
      and overall competence based on a nominal scale. The untaught construct of
      cultural desire showed the most significant improvement.

PMID- 20143756
TI  - Planning a study abroad clinical experience.
AB  - Not only is globalization expanding areas of human activity, it is also
      influencing the variety of educational offerings in universities. Therefore,
      globalization must be considered by nurse educators as they reevaluate ways of
      preparing nursing students to meet the health care needs of populations they
      currently serve and will care for in the future. Study abroad programs have been
      encouraged to be part of the college experience in the United States for more
      than 30 years; however, these programs have been relatively lacking in nursing
      education. Most of the study abroad programs described in the nursing literature
      are research-based or first-person accounts of an experience and provide little
      information about planning a study abroad program. This article describes a study
      abroad learning experience for senior nursing students and discusses the issues
      such as student selection, student safety, and available clinical experiences
      that need to be considered before undertaking such an endeavor.

PMID- 20143757
TI  - The course council: an example of student-centered learning.
AB  - To promote student-centered learning, a course council was established in a
      beginning undergraduate nursing course. A student representative was selected by
      peers to attend a monthly course council meeting with faculty. Representatives
      were asked to query classmates in their section of eight students regarding
      opinions, questions, and concerns about the course and then bring those views to
      the council. In this monthly, small group, open dialogue setting, students spoke
      freely about experiences in the classroom, laboratory, and clinical settings. The
      stage was set for reflection, problem solving, and decision making involving
      students and faculty. Student input led to meaningful course changes, provided
      opportunities for students to learn from one another, and fostered critical
      thinking and professional responsibility. The course council approach was
      successful and has been expanded to include other nursing courses.

PMID- 20143758
TI  - A community-wide academic-service partnership to expand faculty and student
      capacity.
AB  - This article describes a unique academic-service community collaborative aimed at
      increasing student and faculty capacity. The state hospital association held a
      series of community-wide meetings with health care organization and academic
      leaders to discuss the growing RN and faculty shortages. Collectively, schools of
      nursing experienced a 70% increase in qualified applicants and could not admit
      all qualified applicants due to faculty constraints. A unique Workforce
      Collaborative Pilot Project was formed to address student and faculty capacity
      issues with three primary objectives: expand the pool of educators involved in
      preparing the next generation of nurses, increase nursing school enrollments by
      335 additional nursing students each year in the metropolitan area for the next 5
      years, and implement an innovative educational model that could be sustained or
      replicated. As a result, area schools of nursing have expanded enrollment by
      1,046, and overall quality measurements and evaluative feedback remain positive.

PMID- 20143759
TI  - Cultural diversity in nursing education: perils, pitfalls, and pearls.
AB  - Increasing diversity in the classroom challenges nursing educators to identify
      issues that complicate teaching (perils), analyze barriers for themselves and
      their students (pitfalls), and select new strategies for working with
      nontraditional students (pearls). This article identifies concerns arising from
      attitudes and values within nursing and common approaches to diversity education,
      and then discusses key issues in nursing education that relate to human nature,
      culture, faculty workload, and student demographics. Finally, some strategies are
      proposed for increasing the effectiveness of professional preparation with
      diverse students through a focus on culturally congruent education and
      development of faculty cultural competence.

PMID- 20143760
TI  - Promising practices for faculty in accelerated nursing programs.
AB  - Accelerated nursing programs for college graduates have been graduating RNs since
      1971. The question of how best to educate this cohort is a concern and even more
      of a priority because these students have different learning needs. Anecdotally,
      faculty know accelerated students tend to be challenging to teach. Administrators
      of nursing programs also are aware that some faculty prefers teaching this cohort
      and other faculty does not. This descriptive qualitative study collected data
      during focus groups using an open-ended interview guide. The focus groups
      consisted of accelerated second-degree nursing students. Participants identified
      six themes as best faculty practices: appreciate accelerated students as adult
      learners, communicate passion for the profession, challenge and motivate,
      practice while teaching and share their experiences, support accelerated
      students, and use varied teaching styles.

PMID- 20143761
TI  - Posterior polymorphous dystrophy and keratoglobus in a child.
AB  - A 13-year-old boy presented with gradually progressive deterioration of vision in
      both eyes, bilateral photophobia, and regular headaches. Clinical examination,
      anterior segment findings, and specular microscopy findings were consistent with
      the diagnosis of posterior polymorphous dystrophy and keratoglobus. To the
      authors' knowledge, this is the first pediatric case and the second case overall
      of the simultaneous occurrence of posterior polymorphous dystrophy and
      keratoglobus. 

PMID- 20143762
TI  - Abnormal posterior insertion of the lateral rectus muscle.
AB  - Ectopic insertion of the lateral rectus muscle is a rare congenital abnormality.
      The authors present the case of an exotropic patient with an abnormal posterior
      insertion of the lateral rectus muscle. 

PMID- 20143763
TI  - Convergence excess esotropia: a proposed new classification and the effect of
      monocular occlusion on the Ac/A ratio.
AB  - BACKGROUND: Convergence excess esotropia defines an esotropia on accommodation at
      near fixation with binocular single vision and motor fusion at distance fixation
      associated with a high accommodative convergence: accommodation (Ac/A) ratio. The
      effect of occlusion on exotropia has been well described and is known to alter
      the Ac/A ratio. This study examines the effect of monocular occlusion on
      convergence excess esotropia. METHODS: The Ac/A ratio was measured using the
      gradient method at 1/3 and 6 m in 10 patients with convergence excess esotropia
      immediately prior to and following a 30-minute period of monocular occlusion.
      RESULTS: Clinically and statistically significant differences to the angle of
      deviation and the Ac/A ratio were found in some patients following occlusion.
      CONCLUSION: Ac/A ratio measurement in convergence excess esotropia is influenced
      by fusional tenacity. Disrupting this fusion with a period of monocular occlusion
      results in changes to the angle of deviation in some patients, suggesting
      subcategorization of this condition into true and simulated convergence excess
      esotropia. Measurements of the Ac/A ratio are influenced by fixation distance.

PMID- 20143764
TI  - Conjunctival marginal zone b-cell lymphoma in a 13-year-old child.
AB  - Ocular adnexal lymphoma is a hematopoietic tumor that arises in the conjunctiva,
      orbit, eyelid, lacrimal gland, or lacrimal sac. The treatment options in children
      have not been addressed in the literature. The authors describe a 13-year-old
      child with ocular adnexal lymphoma and discuss the treatment options. 

PMID- 20143765
TI  - Augmentin duoTM in the treatment of childhood blepharokeratoconjunctivitis.
AB  - PURPOSE: To report the use of Augmentin Duo 400/57 (GlaxoSmithKline, Middlesex,
      UK) in the treatment of childhood blepharokeratoconjunctivitis (BKC). METHODS:
      This is a retrospective interventional case series. The case notes of 7
      consecutive patients treated with Augmentin Duo 400/57 for BKC during 18 months
      were reviewed. Diagnostic criteria for BKC were blepharitis including recurrent
      chalazia and meibomian gland dysfunction, eyelid margin telangiectasia and facial
      rosacea, recurrent episodes of chronic red eye, photophobia, watering, punctate
      superficial keratopathy, corneal neovascularization, and corneal ulcers. RESULTS:
      Seven children (age range: 6 to 14 years) were diagnosed as having BKC. All
      children received systemic Augmentin Duo 400/57 and showed considerable
      improvement within the first month of therapy. Six children had no recurrences
      during a mean follow-up of 6 months. No patients experienced any side effects
      from this treatment. CONCLUSIONS: Augmentin Duo 400/57 has not previously been
      reported in the treatment of BKC in children. In this case series, Augmentin Duo
      400/57 proved to be at least as effective as current treatments with systemic
      erythromycin or doxycycline with the advantage of a twice-daily dosage and a
      superior side-effect profile.

PMID- 20143767
TI  - Syllabus selection: innovative learning activity.

PMID- 20143770
TI  - Base-induced mechanistic variation in palladium-catalyzed carbonylation of aryl
      iodides.
AB  - A mechanism, which is distinct from the traditional one when sodium alkoxide was
      used instead of tertiary amines, was proposed for the alkoxycarbonylation of aryl
      iodides. The catalytic cycle was composed of oxidative addition, subsequent
      ArPdOR formation, CO insertion to Pd-OR, and final reductive elimination of
      ArPdCOOR. The kinetic simultaneity of the formation of deiodinated side product
      from the aryl iodide and aldehyde from corresponding alcohol provided strong
      evidence for the existence of ArPdOR species. The observation of thioether, as
      the other competitive product in palladium catalyzed thiocarbonylation of aryl
      iodides and sodium alkylthiolate, also indicate the possibility of metathesis
      between ArPdI and sodium alkylthiolate. Preliminary kinetic studies revealed that
      neither oxidative addition nor reductive elimination was rate limiting. DFT
      calculation displayed preference for CO insertion into Pd-OR bond. The advantage
      of this novel mechanism had been demonstrated in the facile alkoxycarbonylation
      and thiocarbonylation. The ethoxycarbonylation of aryl iodides under room
      temperature and balloon pressure of CO in the presence of EtONa were examined,
      and good to high yields were obtained; the t-butoxycarbonylation reactions in the
      presence of t-BuONa were achieved, and the alkylthiocarbonylation (including the
      t-butylthiocarbonylation) of aryl iodides in the presence of sodium alkylthiolate
      were also investigated.

PMID- 20143771
TI  - Chemical degradation of drinking water disinfection byproducts by millimeter
      sized particles of iron-silicon and magnesium-aluminum alloys.
AB  - The candidature of Fe-Si and Mg-Al alloys at millimeter-scale particle sizes for
      chemical degradation of disinfection byproducts (DBPs) in drinking water systems
      was substantiated by their enhanced corrosion resistance and catalytic effect on
      the degradation. The Mg-Al particles supplied electrons for reductive
      degradation, and the Fe-Si particles acted as a catalyst and provided the sites
      for the reaction. The alloy particles are obtained by mechanical milling and
      stable under ambient conditions. The proposed method for chemical degradation of
      DBPs possesses the advantages of relatively constant degradation performance,
      long-term durability, no secondary contamination, and ease of handling, storage
      and maintenance in comparison with nanoparticle systems.

PMID- 20143772
TI  - Large scale crystallinity in kinetically stable polythiophene-based Langmuir
      Blodgett films.
AB  - The first direct observation of large scale molecular level ordering in a complex
      poly(3-alkylthiophene)-based thin film is reported. The fabrication and
      characterization of highly ordered thin films made from the regioregular,
      amphiphilic polythiophene derivative poly(3-(11-(2
      tetrahydropyranyloxy)undecyl)thiophene) (PTHPUDT) are described. PTHPUDT affords
      kinetically stable, high optical quality films deposited layer-by-layer using the
      Langmuir-Blodgett (LB) method. X-ray diffraction studies confirm the deposition
      of a film with long-range order normal to the surface, characterized by bilayer
      separations of approximately 30 A. The films display in-plane anisotropy,
      associated with the preferential alignment of the polymer main chain in the
      dipping direction. Molecular resolution atomic force microscopy shows the
      presence of highly ordered crystalline domains within the plane, consistent with
      an ordered array of parallel, closed-packed, polythiophene chains. Polarized
      optical microscopy confirms the formation of large scale domains that display
      uniform optical retardation across macroscopic length scales. FeCl(3)-doped films
      yield anisotropic conduction behavior, suggesting higher rates of transport
      perpendicular to the main chain direction. The kinetic stability of these films
      is distinct from films of other polythiophenes, other deposition methods, and
      simpler amphiphiles, all of which tend toward their bulk, thermodynamically
      stable structures. This stability and long-range order are attributed to the
      amphiphilic nature of the polymer and the dimensional restrictions of the
      polymer's main chain, which limits the extent of structural defect-based
      reorganization, and the limited number of local structures of the alkyl chains.
      The degree and nature of the ordering in these semicrystalline films make them an
      ideal model system in which to elucidate the connection between morphology and
      physical property in complex pi-conjugated polymers.

PMID- 20143773
TI  - Influence of variety, location, growing year, and storage on the total
      phosphorus, phytate-phosphorus, and phytate-phosphorus to total phosphorus ratio
      in rice.
AB  - The influence of variety, location, growing year, and storage on the total
      phosphorus (total P), phytate-P, and phytate-P to total P ratio in Korean rice
      varieties was investigated. Experiment 1 investigated the influence of 9 rice
      varieties, 4 locations, and 2 growing years. In experiment 2, the effect of
      storage for 1, 6, and 12 months was examined. Results showed that locations,
      varieties, and their interactions had a significant effect on the total P and
      phytate-P contents in rice, whereas growing year did not. Location had a higher
      effect than variety. Rice grown at locations with higher precipitation levels and
      higher temperatures obtained lower total P, phytate-P, and phytate-P to total P
      ratio. Effect of variety and location showed the possibility of reducing phytate
      P in rice. Storage of rice for up to 12 months did not affect the total P and
      phytate-P concentrations of rice.

PMID- 20143774
TI  - Extraction and analysis of auxins in plants using dispersive liquid-liquid
      microextraction followed by high-performance liquid chromatography with
      fluorescence detection.
AB  - Auxin plays an important role in cell differentiation, apical dominance, and
      tropism in plants. A new method based on dispersive liquid-liquid microextraction
      (DLLME) combined with high-performance liquid chromatography-fluorescence
      detection (HPLC-FLD) has been established to detect auxin. A mixture of CHCl(3)
      (extraction solvent) and acetone (disperser solvent) was injected quickly into a
      sample solution with desired salt concentration and pH value, and then a cloudy
      solution consisting of many dispersed fine droplets of CHCl(3) was formed. After
      centrifugation, the sedimented phase was withdrawn and directly analyzed by HPLC
      FLD. Under optimal conditions, four auxins were baseline separated within 3.5
      min, with the minimal limit of detection of 0.02 ng mL(-1) and coefficient
      correlations in the range of 0.9980-0.9995. This simple method was successfully
      applied to real sample analysis. Experimental results showed that DLLME was a
      high-performance and powerful preconcentration method to extract and enrich
      related plant auxin.

PMID- 20143775
TI  - Plasmonic field enhancement of the exciton-exciton annihilation process in a
      poly(p-phenyleneethynylene) fluorescent polymer by Ag nanocubes.
AB  - Using the Langmuir-Blodgett (LB) technique, a poly(paraphenyleneethynylene) (PPE)
      fluorescent conjugated polymer was assembled on either a quartz substrate (system
      I) or on the surface of silver nanocube (AgNC) monolayers (system II). The
      fluorescence intensity of the polymer was studied in system I as a function of
      the surface density of the polymer sample when deposited on quartz substrates and
      in system II on the surface coverage of the underlying AgNC monolayers. In system
      I, a continual increase in the fluorescence intensity is observed as the surface
      density of excited polymer is increased. In system II, the fluorescence intensity
      of the polymer first increased until a threshold surface coverage of AgNC was
      reached, after which it decreased rapidly with increasing surface coverage in the
      AgNC monolayer. The exciting light intensity dependence is studied before and
      after this threshold in system II. The results suggest that one-photon processes
      were responsible for the increased intensity before the threshold, and two-photon
      processes were responsible for the rapid decrease in the polymer fluorescence
      intensity after the threshold. These observations are explained by the increase
      of the surface plasmon enhancement of the exciting light intensity as the
      nanoparticle surface coverage is increased. In turn, this increases the polymer
      absorption rate, which results in a continuous increase in the exciton density
      and is evident by an increase in the fluorescence intensity. At the threshold,
      the increased exciton density leads to an increase in the rate of exciton-exciton
      collisions, which leads to exciton-exciton annihilations. When this phenomenon
      becomes faster than the rate of fluorescence emission, an intensity decrease is
      observed. By exploiting the surface plasmon enhancement of absorption processes,
      we have observed the first exciton-exciton annihilation using a low-intensity Hg
      lamp continuous wave source.

PMID- 20143776
TI  - Decrease of aged beer aroma by the reducing activity of brewing yeast.
AB  - The flavor profile of beer is subject to changes during storage. Since, possibly,
      yeast has an influence on flavor stability, the aim of this study was to examine
      if there is a direct impact of brewing yeast on aged aroma. This was achieved by
      refermentation of aged beers. It was shown that several aged aroma notes, such as
      cardboard, ribes, Maillard and Madeira, were removed almost entirely by brewing
      yeast, independently of the yeast or the beer type. This was explained by the
      reduction of aldehydes, mainly (E)-2-nonenal, Strecker aldehydes, 5
      hydroxymethylfurfural and diacetyl, to their corresponding alcohols. Furthermore,
      it became evident that the reducing capacity of brewing yeast is high, but that
      yeast strain and compound specific residual concentrations remained in the
      refermented beer independently of the initial concentration. Finally, it appeared
      that aldehydes were not only reduced but also formed during refermentation.

PMID- 20143777
TI  - An acidophilic and acid-stable beta-mannanase from phialophora sp. p13 with high
      mannan hydrolysis activity under simulated gastric conditions.
AB  - A beta-mannanase gene, man5AP13, was cloned from Phialophora sp. P13 and
      expressed in Pichia pastoris. The deduced amino acid sequence of the mature
      enzyme, MAN5AP13, had highest identity (53%) with the glycoside hydrolase family
      5 beta-mannanase from Bispora sp. MEY-1. The purified recombinant beta-mannanase
      was acidophilic and acid stable, exhibiting maximal activity at pH 1.5 and
      retaining >60% of the initial activity over the pH range 1.5-7.0. The optimum
      temperature was 60 degrees C. The specific activity, K(m) and V(max) for locust
      bean gum substrate were 851 U/mg, 2.5 mg/mL, and 1667.7 U/min.mg, respectively.
      The enzyme had excellent activity and stability under simulated gastric
      conditions, and the released reducing sugar of locust bean gum was significantly
      enhanced by one-fold in simulated gastric fluid containing pepsin in contrast to
      that without pepsin. All these properties make MAN5AP13 a potential additive for
      use in the food and feed industries.

PMID- 20143778
TI  - Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N
      hydroxyheptanamide (CUDc-101) as a potent multi-acting HDAC, EGFR, and HER2
      inhibitor for the treatment of cancer.
AB  - By incorporating histone deacetylase (HDAC) inhibitory functionality into the
      pharmacophore of the epidermal growth factor receptor (EGFR) and human epidermal
      growth factor receptor 2 (HER2) inhibitors, we synthesized a novel series of
      compounds with potent, multiacting HDAC, EGFR, and HER2 inhibition and identified
      7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide 8
      (CUDC-101) as a drug candidate, which is now in clinical development. 8 displays
      potent in vitro inhibitory activity against HDAC, EGFR, and HER2 with an IC(50)
      of 4.4, 2.4, and 15.7 nM, respectively. In most tumor cell lines tested, 8
      exhibits efficient antiproliferative activity with greater potency than
      vorinostat (SAHA), erlotinib, lapatinib, and combinations of vorinostat/erlotinib
      and vorinostat/lapatinib. In vivo, 8 promotes tumor regression or inhibition in
      various cancer xenograft models including nonsmall cell lung cancer (NSCLC),
      liver, breast, head and neck, colon, and pancreatic cancers. These results
      suggest that a single compound that simultaneously inhibits HDAC, EGFR, and HER2
      may offer greater therapeutic benefits in cancer over single-acting agents
      through the interference with multiple pathways and potential synergy among HDAC
      and EGFR/HER2 inhibitors.

PMID- 20143779
TI  - Synthesis and evaluation of paracetamol esters as novel fatty acid amide
      hydrolase inhibitors.
AB  - Fatty acid amide hydrolase (FAAH) is the key hydrolytic enzyme for the endogenous
      cannabinoid receptor ligand anandamide. The synthesis and evaluation for their
      FAAH inhibitory activities of a series of 18 paracetamol esters are described.
      Structure-activity relationship studies indicated that the ester (33) with a 2-(4
      (2-(trifluoromethyl)pyridin-4-ylamino)phenyl)acetic acid substituent was the most
      potent analogue in this series. The compound inhibited FAAH activity in a
      competitive manner with a K(i) value of 0.16 microM. The compound was also able
      to inhibit the FAAH activity in rat basophilic leukemia cells as assessed by
      measuring either the hydrolysis of anandamide, the FAAH-dependent cellular
      accumulation of anandamide, or the FAAH-dependent recycling of tritium to the
      cell membranes. The compound also inhibited the activity of monoacylglycerol
      lipase (MGL), the enzyme responsible for the hydrolysis of the endogenous
      cannabinoid receptor ligand 2-arachidonoylglycerol, with an IC(50) value of 1.9
      microM. It is concluded that the compound may be a useful template for the design
      of potent novel inhibitors of FAAH.

PMID- 20143780
TI  - Silicon photonic microring resonators for quantitative cytokine detection and T
      cell secretion analysis.
AB  - The ability to perform multiple simultaneous protein biomarker measurements in
      complex media with picomolar sensitivity presents a large challenge to disease
      diagnostics and fundamental biological studies. Silicon photonic microring
      resonators represent a promising platform for real-time detection of biomolecules
      on account of their spectral sensitivity toward surface binding events between a
      target and antibody-modified microrings. For all refractive index-based sensing
      schemes, the mass of bound analytes, in combination with other factors such as
      antibody affinity and surface density, contributes to the observed signal and
      measurement sensitivity. Therefore, proteins that are simultaneously low in
      abundance and have a lower molecular weight are often challenging to detect. By
      employing a more massive secondary antibody to amplify the signal arising from
      the initial binding event, it is possible to improve both the sensitivity and the
      specificity of protein assays, allowing for quantitative sensing in complex
      sample matrices. Herein, a sandwich assay is used to detect the 15.5 kDa human
      cytokine interleukin-2 (IL-2) at concentrations down to 100 pg/mL (6.5 pM) and to
      quantitate unknown solution concentrations over a dynamic range spanning 2.5
      orders of magnitude. This same sandwich assay is then used to monitor the
      temporal secretion profile of IL-2 from Jurkat T lymphocytes in serum-containing
      cell culture media in the presence of the entire Jurkat secretome. The same
      temporal secretion analysis is performed in parallel using a commercial ELISA,
      revealing similar IL-2 concentration profiles but superior precision for the
      microring resonator sensing platform. Furthermore, we demonstrate the generality
      of the sandwich assay methodology on the microring resonator platform for the
      analysis of any biomolecular target for which two high-affinity antibodies exist
      by detecting the approximately 8 kDa cytokine interleukin-8 (IL-8) with a limit
      of detection and dynamic range similar to that of IL-2. This work demonstrates
      the first application of silicon photonic microring resonators for detecting
      cellular secretion of cytokines and represents an important advance for the
      detection of protein biomarkers on an emerging analytical platform.

PMID- 20143781
TI  - Simultaneous quantification of intracellular natural and antiretroviral
      nucleosides and nucleotides by liquid chromatography-tandem mass spectrometry.
AB  - Nucleoside reverse transcriptase inhibitors (NRTI) require intracellular
      phosphorylation, which involves multiple enzymatic steps to inhibit the human
      immunodeficiency virus type 1 (HIV-1). NRTI-triphosphates (NRTI-TP) compete with
      endogenous 2'-deoxyribonucleosides-5'-triphosphates (dNTP) for incorporation by
      the HIV-1 reverse transcriptase (RT). Thus, a highly sensitive analytical
      methodology capable of quantifying at the low femtomoles/10(6) cells level was
      necessary to understand the intracellular metabolism and antiviral activity of
      NRTIs in human peripheral blood mononuclear (PBM) cells and in macrophages. A
      novel, rapid, and a reproducible ion-pair chromatography-tandem mass spectrometry
      (MS/MS) method was developed to simultaneously quantify the intracellular
      phosphorylated metabolites of abacavir, emtricitabine, tenofovir disoproxil
      fumarate, amdoxovir, and zidovudine, as well as four natural endogenous dNTP.
      Positive or negative electrospray ionization was chosen with specific MS/MS
      transitions for improved selectivity on all the compounds studied. The sample
      preparation, the ion-pair reagent concentration, and buffer composition were
      optimized, resulting in the simultaneous quantification of 13 different
      nucleotides in a total run time of 30 min. This novel method demonstrated optimal
      sensitivity (limit of detection 1-10 nM for various analytes), specificity, and
      reproducibility to successfully measure NRTI-TP and dNTP in human PBM cells and
      macrophages.

PMID- 20143782
TI  - Discovery of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4
      difluorophenyl)urea (nelotanserin) and related 5-hydroxytryptamine2A inverse
      agonists for the treatment of insomnia.
AB  - Insomnia affects a growing portion of the adult population in the U.S. Most
      current therapeutic approaches to insomnia primarily address sleep onset latency.
      Through the 5-hydroxytryptamine(2A) (5-HT(2A)) receptor, serotonin (5-HT) plays a
      role in the regulation of sleep architecture, and antagonists/inverse-agonists of
      5-HT(2A) have been shown to enhance slow wave sleep (SWS). We describe here a
      series of 5-HT(2A) inverse-agonists that when dosed in rats, both consolidate the
      stages of NREM sleep, resulting in fewer awakenings, and increase a physiological
      measure of sleep intensity. These studies resulted in the discovery of 1-[3-(4
      bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea
      (Nelotanserin), a potent inverse-agonist of 5-HT(2A) that was advanced into
      clinical trials for the treatment of insomnia.

PMID- 20143783
TI  - Cold- and overfeeding-induced changes in the human skeletal muscle proteome.
AB  - Adaptive thermogenesis, the increase in energy expenditure in response to diet or
      cold exposure, shows large interindividual differences. The objective of this
      study was to investigate the proteins in human muscle tissue that relate to this
      variation. Therefore, we studied correlations between changes in expressions of
      proteins and increases in energy expenditure. This, in proteomic research,
      innovative application of widely used statistical approaches optimized the
      information yield in this study. The metabolic responses to cold and overfeeding
      in 9 lean adult male subjects were measured in a respiration chamber in a
      baseline condition, during three days of cold exposure and during three days of
      overfeeding. After each respiration chamber measurement a muscle biopsy was
      taken, from which proteins were isolated and separated using 2D gel
      electrophoresis. Ninety-five spots that were significantly changed were analyzed
      using MALDI-TOF/TOF mass spectrometry. Of these proteins, 52 have been
      identified. Remarkably, many of the identified proteins that changed in
      expression significantly after overfeeding and after cold exposure are part of
      the glycolytic pathway. However, the identified proteins are not considered to be
      rate limiting. After overfeeding, the abundance of these glycolytic proteins
      increased. Upon cold exposure, differences in glycolytic protein concentrations
      related significantly to the interindividual differences in cold-induced adaptive
      thermogenesis. Moreover, increased abundance of ATP synthase subunits suggested
      an increased ATP-production. This shows that upon cold exposure ATP utilizing
      processes might be involved that were not apparent in the baseline situation. The
      results of this study stress the importance of changes in glycolytic proteins in
      both cold- and overfeeding-induced adaptive thermogenesis.

PMID- 20143784
TI  - The crucial role of dispersion in the cohesion of nonbridged binuclear Os --> Cr
      and Os --> W adducts.
AB  - The concept of a dative metal-metal bond is generally used to designate the donor
      acceptor (DA) interaction of an electron-saturated metal center with another
      electron-deficient--or unsaturated--metal center. This type of DA bonding
      extended to the field of coordination complexes constitutes a borderline case of
      weak metal-metal interaction, among which the so-called metallophilic
      interactions occurring with 4d, 5d, and other late-transition-metal complexes are
      the most documented and representative examples. From a general standpoint, the
      peculiar position of the so-called dative metal-metal bond in chemical bonding
      stems from its presumed covalent character, which contrasts with the situation
      encountered with metallophilic interactions, which are essentially supported by
      dispersion and electrostatic forces and somewhat sustained by relativistic
      effects. In this study, the nature of the metal-metal bond in nonbridged 5d-3d Os
      Cr and 5d-5d Os-W adducts, i.e., (Me(3)P)(CO)(4)Os-M(CO)(5) (M = Cr, W) and
      (CO)(5)Os-Cr(CO)(5), was addressed by resorting to state-of-the-art quantum
      chemical methods. Semilocal density functional theory (DFT) approximations like
      Becke-Perdew or TPSS, the double-hybrid B2PLYP functional, as well as the
      corresponding dispersion, including TPSS-D and B2PLYP-D functionals and the wave
      function-based spin-component-scaled second-order perturbative Moller-Plesset
      theory (SCS-MP2), were used. Energy decomposition analysis combined with the
      analysis of pairwise interfragment correlation energies from Pipek-Mezey
      localized molecular orbitals in combination with SCS-MP2 led to a clear
      demonstration of the significant role of dispersion (London) forces in the
      stabilization of the title adducts, wherein the Os-metal DA bond bears a rather
      low covalent character. These results plead in favor of a systematic recourse to
      dispersion including DFT approximations when addressing organometallic and
      coordination complexes.

PMID- 20143785
TI  - Rational conversion of affinity reagents into label-free sensors for Peptide
      motifs by designed allostery.
AB  - Optical biosensors for short peptide motifs, an important class of biomarkers,
      have been developed based on "affinity clamps", a new class of recombinant
      affinity reagents. Affinity clamps are engineered by linking a peptide-binding
      domain and an antibody mimic domain based on the fibronectin type III scaffold,
      followed by optimization of the interface between the two. This two-domain
      architecture allows for the design of allosteric coupling of peptide binding to
      fluorescence energy transfer between two fluorescent proteins attached to the
      affinity clamp. Coupled with high affinity and specificity of the underlying
      affinity clamps and rationally designed mutants with different sensitivity,
      peptide concentrations in crude cell lysate were determined with a low nanomolar
      detection limit and over 3 orders of magnitude. Because diverse affinity clamps
      can be engineered, our strategy provides a general platform to generate a
      repertoire of genetically encoded, label-free sensors for peptide motifs.

PMID- 20143786
TI  - Influence of the stabilizer concentration on the internal liquid crystalline
      order and the size of oil-loaded monolinolein-based dispersions.
AB  - The internal phase of monolinolein-based dispersions loaded with tetradecane or
      (R)-(+)-limonene was investigated as a function of the stabilizer content by
      small-angle X-ray scattering. Phase transitions at the colloidal scale were found
      in some of nanostructured aqueous dispersions by increasing the stabilizer
      content. For particles containing a bicontinuous cubic phase, a large increase of
      the stabilizer concentration promoted a liquid crystalline phase transition from
      the Pn3m to the Im3m cubic symmetry. The coexistence of both phases is observed
      in an intermediate stabilizer concentration range. For particles with an internal
      micellar cubic Fd3m symmetry, the internal structure changes in the isotropic
      fluid L(2) phase. In case of particles with an internal hexagonal phase (H(2)
      symmetry), the increasing amount of stabilizer did not alter the lattice
      parameter but decreased the size of the nanostructured domain. Moreover, we
      showed for hexagonal and emulsified micellar phase particles that the increase of
      the stabilizer content induced a strong decrease of the mean hydrodynamic size of
      the particles, allowing producing nanostructured lipid-based liquid crystalline
      particles down to a radius of 70 nm at the same energy input.

PMID- 20143787
TI  - Gamma-deprotonation of anionic bis(trimethylsilyl)amidolanthanide complexes with
      a countered [(Tp(Me2))2Ln]+ cation.
AB  - Tp(Me2)LnCl(2) (1) reacts with 2 equiv of KN(SiMe(3))(2) in tetrahydrofuran at
      room temperature to yield the ligand redistribution/gamma-deprotonation products
      [(Tp(Me2))(2)Ln](+)[((Me(3)Si)(2)N)(2)Ln(CH(2))SiMe(2)N(SiMe(3))](-) [Ln = Er
      (2), Y (3)]. Complex 2 can also be obtained by reacting [(Me(3)Si)(2)N](2)ErCl
      with KTp(Me2). However, 1 reacts with 1.5 and 1 equiv of KN(SiMe(3))(2) to yield
      [(Tp(Me2))(2)Er](+)[((Me(3)Si)(2)N)(3)ErCl](-) (4) and
      [(Tp(Me2))(2)Er](+){[(Me(3)Si)(2)N)Tp(Me2)ErCl](2)(mu-Cl)(2)K}(-) (5),
      respectively. Furthermore, it is found that 2 reacts with 2 equiv of CyN=C=NCy
      (Cy = cyclohexyl) to give the tandem HN(SiMe(3))(2) elimination and Ln-C
      insertion product (Tp(Me2))Er[(CyN)(2)CCH(2)SiMe(2)N(SiMe(3))] (6) in 71%
      isolated yield. The results reveal that the gamma-deprotonation degree of
      advancement increases with an increase of the steric hindrance around the central
      metal ion. All new complexes have been characterized by elemental analysis and
      spectroscopic properties, and their solid-state structures have also been
      determined through single-crystal X-ray diffraction analysis.

PMID- 20143788
TI  - Patterned growth of vertically aligned organic nanowire waveguide arrays.
AB  - Vertical nanowire arrays were prepared from an organic dye compound, 1,5
      diaminoanthraquinone (DAAQ), on various types of substrates by a facile physical
      vapor transport method. It was found that the DAAQ grows much faster on the
      substrates with higher surface energies. Therefore, patterned growth of the
      nanowire arrays was achieved by modifying the substrate surfaces both
      geometrically and chemically to induce selective growth in areas of higher
      surface energies. The DAAQ nanowires can serve as nanosized active optical
      waveguides that allow the locally excited photoluminescence to propagate along
      the length of the wires. The low-loss waveguide propagation modes along the
      nanowire were observed experimentally. The nanowire arrays can be integrated
      directly with a portable fiber optics spectrometer for chemical vapor sensing.

PMID- 20143789
TI  - Biscarbene palladium(II) complexes. reactivity of saturated versus unsaturated N
      heterocyclic carbenes.
AB  - A series of designed palladium biscarbene complexes including saturated and
      unsaturated N-heterocyclic carbene (NHC) moieties have been prepared by the
      carbene transfer methods. All of these complexes have been characterized by (1)H
      and (13)C NMR spectroscopy as well as X-ray diffraction analysis. The reactivity
      of Pd-C((saturated NHC)) is distinct from that of Pd-C((unsaturated NHC)). The Pd
      C((saturated NHC)) bonds are fairly stable toward reagents such as CF(3)COOH,
      AgBF(4) and I(2), whereas Pd-C((unsaturated NHC)) bonds are readily cleaved under
      the similar conditions. Notably, the catalytically activity of these palladium
      complexes on Suzuki-Miyaura coupling follows the order: (sat-NHC)(2)PdCl(2) >
      (sat-NHC)(unsat-NHC)PdCl(2 )> (unsat-NHC)(2)PdCl(2).

PMID- 20143790
TI  - Synthesis and biological evaluation of heteroanalogues of kotalanol and de-O
      sulfonated kotalanol.
AB  - The synthesis of nitrogen and selenium analogues of kotalanol and de-O-sulfonated
      kotalanol, naturally occurring sulfonium-ion glucosidase inhibitors isolated from
      Salacia reticulata, and their evaluation as glucosidase inhibitors against the N
      terminal catalytic domain of human maltase glucoamylase (ntMGAM) are described.

PMID- 20143791
TI  - Cyclometalated cluster complex with a butterfly-shaped Pt2Ag2 core.
AB  - The cyclometalated platinum complex [PtMe(bhq)(dppy)] (1), in which bhq =
      benzo{h}quinoline and dppy = 2-(diphenylphosphino)pyridine, was prepared by the
      reaction of [PtMe(SMe(2))(bhq)] with 1 equiv of dppy at room temperature. Complex
      1 contains one free pyridyl unit and was readily characterized by multinuclear
      NMR spectroscopy and elemental microanalysis. The reaction of complex 1 with 1
      equiv of [Ag(CH(3)CN)(4)]BF(4) gave the cyclometalated cluster complex
      [Pt(2)Me(2)(bhq)(2)(mu-dppy)(2)Ag(2)(mu-acetone)](BF(4))(2) (2) in 70% yield. The
      crystal structure of complex 2 was determined by X-ray crystallography,
      indicating a rare example of a butterfly cluster with a Pt(2)Ag(2) core in which
      the Ag atoms occupy the edge-sharing bond. In solution, the bridging acetone
      dissociates from the cluster complex 2, but as shown by NMR spectroscopy, the
      Pt(2)Ag(2) core is retained in solution and a dynamic equilibrium is suggested to
      be established between the planar and butterfly skeletal geometries.

PMID- 20143792
TI  - Synthesis of platinum cubes, polypods, cuboctahedrons, and raspberries assisted
      by cobalt nanocrystals.
AB  - The introduction of metallic traces into the synthesis of platinum nanocrystals
      (Pt NCs) has been investigated as a surfactant-independent means of controlling
      shape. Various nanocrystal morphologies have been produced without modification
      of the reaction conditions, composition, and concentration other than the
      presence of cobalt traces (<5%). In the presence of metallic cobalt (a strong
      reducer for Pt cations) cubic Pt NCs are obtained, while cobalt ions or gold NCs
      have no effect on the synthesis, and as a result, polypods are obtained.
      Intermediate shapes such as cemented cubes or cuboctahedron NCs are also obtained
      under similar conditions. Thus, various NC shapes can be obtained with subtle
      changes, which illustrates the high susceptibility and mutability of the NC shape
      to modification of the reaction kinetics during the early reduction process. Our
      studies help progress toward a general mechanism for nanocrystal shape control.

PMID- 20143793
TI  - Synthesis of gamma,delta-unsaturated glycolic acids via sequenced brook and
      Ireland--claisen rearrangements.
AB  - Organozinc, -magnesium, and -lithium nucleophiles initiate a Brook/Ireland
      Claisen rearrangement sequence of allylic silyl glyoxylates resulting in the
      formation of gamma,delta-unsaturated alpha-silyloxy acids.

PMID- 20143794
TI  - Dynamic labeling strategy with 204Hg-isotopic methylmercurithiosalicylate for
      absolute peptide and protein quantification.
AB  - The methylmercury ion (CH(3)Hg(+)) demonstrated a high efficiency for directly
      labeling peptide/protein based on its specific and strong interaction with the
      sulfhydryl(s) in the peptide/protein and because of its smallest size among
      monofunctional organic mercurials studied, including methylmercury, ethylmercury,
      4-(hydroxymercuric)benzoic acid, and 2,7-dibromo-4-hydroxymercurifluoresceine
      disodium. A simple 1:1 stoichiometry between CH(3)Hg(+) and sulfhydryl, confirmed
      with electrospray ionization-mass spectrometry (ESI-MS) and matrix-assisted laser
      desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) studies,
      made it easy to calibrate the stoichiometry of Hg in the peptide/protein. In
      order to avoid the direct use of the harmful CH(3)Hg(+), in this study a
      CH(3)Hg(+)-equivalent tag, methylmercurithiosalicylate (CH(3)Hg-THI), and its
      (204)Hg-enriched homologue (CH(3)(204)Hg-THI) were synthesized, and then
      CH(3)Hg(+) and/or CH(3)(204)Hg(+) released from CH(3)Hg-THI and/or CH(3)(204)Hg
      THI in solution were utilized to demonstrate the dynamic labeling of glutathione
      (GSH) and two model proteins, beta-lactoglobulin (BLG) and ovalbumin (OVA), for
      the first time. Furthermore, the CH(3)(204)Hg-THI isotopical labeled GSH, BLG,
      and OVA standards (CH(3)(204)Hg-GSH, CH(3)(204)Hg-BLG, and CH(3)(204)Hg-OVA) were
      used to demonstrate the feasibility of absolute peptide/protein quantification
      using label-specific isotope dilution inductively coupled plasma mass
      spectrometry (ICPMS). On the basis of the accurate and sensitive determination of
      Hg using ICPMS, the detection limits of GSH, BLG, and OVA could reach 45.4, 45.4,
      and 15.1 pmol L(-1), respectively, suggesting the possibility for low-abundance
      peptide/protein quantification alongside the surefire quantification of moderate
      and highly abundant peptide/protein.

PMID- 20143795
TI  - Application of asymmetric flow-field flow fractionation to the characterization
      of colloidal dispersions undergoing aggregation.
AB  - The characterization of complex colloidal dispersions is a relevant and
      challenging problem in colloidal science. In this work, we show how asymmetric
      flow-field flow fractionation (AF4) coupled to static light scattering can be
      used for this purpose. As an example of complex colloidal dispersions, we have
      chosen two systems undergoing aggregation. The first one is a conventional
      polystyrene latex undergoing reaction-limited aggregation, which leads to the
      formation of fractal clusters with well-known structure. The second one is a
      dispersion of elastomeric colloidal particles made of a polymer with a low glass
      transition temperature, which undergoes coalescence upon aggregation. Samples are
      withdrawn during aggregation at fixed times, fractionated with AF4 using a two
      angle static light scattering unit as a detector. We have shown that from the
      analysis of the ratio between the intensities of the scattered light at the two
      angles the cluster size distribution can be recovered, without any need for
      calibration based on standard elution times, provided that the geometry and
      scattering properties of particles and clusters are known. The nonfractionated
      samples have been characterized also by conventional static and dynamic light
      scattering to determine their average radius of gyration and hydrodynamic radius.
      The size distribution of coalescing particles has been investigated also through
      image analysis of cryo-scanning electron microscopy (SEM) pictures. The average
      radius of gyration and the average hydrodynamic radius of the nonfractionated
      samples have been calculated and successfully compared to the values obtained
      from the size distributions measured by AF4. In addition, the data obtained are
      also in good agreement with calculations made with population balance equations.

PMID- 20143796
TI  - Recovery of nanoparticles made easy.
AB  - Here is demonstrated a novel approach to reversible control over nanoparticle
      (NP) stability, permitting facile recovery for the reuse of inorganic NPs. For
      the first time, the separation of NPs is achieved by suspending the
      nanostructures in a background-supporting colloidal fluid, which itself shows a
      liquid-liquid critical-type phase transition at a temperature T(c) instead of
      using a normal molecular solvent.

PMID- 20143797
TI  - Toward ionic-liquid-based model catalysis: growth, orientation, conformation, and
      interaction mechanism of the [Tf2N]- anion in [BMIM][Tf2N] thin films on a well
      ordered alumina surface.
AB  - Aiming at a better understanding of the interaction of ionic liquid (IL) thin
      films with oxide supports, we have performed a model study under ultrahigh vacuum
      (UHV) conditions. We apply infrared reflection absorption spectroscopy (IRAS) in
      combination with density functional theory (DFT). Thin films of 1-butyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide [BMIM][Tf(2)N] are grown on
      an atomically flat, well-ordered alumina film on NiAl(110) using a novel UHV
      compatible evaporator. Time-resolved IRAS measured during the growth and
      subsequent thermal desorption points toward reversible molecular adsorption and
      desorption. There was no indication of decomposition. The vibrational bands are
      assigned with the help of DFT calculations. Strong relative intensity changes in
      individual [Tf(2)N](-) bands are observed in the monolayer region. This indicates
      pronounced orientation effects for the anion. The adsorption geometry of
      [Tf(2)N](-) is determined on the basis of a detailed comparison with DFT. The
      results suggest that [Tf(2)N](-) anions adopt a cis conformation in the
      submonolayer region. They adsorb in a slightly tilted orientation with respect to
      the surface, mainly interacting with the support via the sulfonyl groups.

PMID- 20143798
TI  - Deciphering excited state evolution in halorhodopsin with stimulated emission
      pumping.
AB  - The primary photochemical dynamics of Hb. pharaonis Halorhodopsin (pHR) are
      investigated by femtosecond visible pump-near IR dump-hyperspectral probe
      spectroscopy. The efficiency of excited state depletion is deduced from transient
      changes in absorption, recorded with and without stimulated emission pumping
      (SEP), as a function of the dump delay. The concomitant reduction of photocycle
      population is assessed by probing the "K" intermediate difference spectrum.
      Results show that the cross section for stimulating emission is nearly constant
      throughout the fluorescent state lifetime. Probing "K" demonstrates that dumping
      produces a proportionate reduction in photocycle yields. We conclude that,
      despite its nonexponential internal conversion (IC) kinetics, the fluorescent
      state in pHR constitutes a single intermediate in the photocycle. This contrasts
      with conclusions drawn from the study of primary events in the related chloride
      pump from Hb. salinarum (sHR), believed to produce the "K" intermediate from a
      distinct short-lived subpopulation in the excited state. Our discoveries
      concerning internal conversion dynamics in pHR are discussed in light of recent
      expectations for similar excited state dynamics in both proteins.

PMID- 20143799
TI  - N-aryl pyrrolo-tetrathiafulvalene based ligands: synthesis and metal
      coordination.
AB  - A straightforward general synthetic access to N-aryl-1,3-dithiolo[4,5-c]pyrrole-2
      thione derivatives 6 from acetylenedicarbaldehyde monoacetal is depicted. In
      addition to their potentiality as precursors to dithioalkyl-pyrrole derivatives,
      thiones 6 are key building blocks to N-aryl monopyrrolo-tetrathiafulvalene
      (MPTTF) derivatives 10. X-ray structures of four of these thiones intermediates,
      reminiscent of the corresponding MPTTF derivatives, are provided. When the aryl
      group is a binding pyridyl unit, the MPTTF derivative 10a can coordinate M(II)
      salts (M = Pt, Pd). The first examples of metal-directed orthogonal MPTTF-based
      dimers 11-14, obtained through coordination of 10a to cis-blocked square planar
      Pt or Pd complexes are described. Studies on the parameters influencing the dimer
      construction are presented, as well as first recognition properties of the
      resulting electron-rich clip for C(60).

PMID- 20143800
TI  - Water-induced relaxation of a degenerate vibration of guanidinium using 2D IR
      echo spectroscopy.
AB  - The nearly degenerate asymmetric stretch vibrations near 1600 cm(-1) of the
      guanidinium cation in D-glycerol/D(2)O mixtures having different viscosity were
      studied by 2D IR photon echo spectroscopy. The polarization-dependent photon echo
      signal shows two separate frequency distributions in the 2D spectrum in D(2)O,
      even though only one band is evident from inspection of the linear FTIR spectrum.
      The split components are more clearly seen at higher viscosity where the
      distortion of the molecule from 3-fold symmetry is even more evident. The
      interactions with solvent induce energy transfer between the degenerate component
      modes on the time scale of 0.5 ps. The energy transfer between modes is directly
      observed in 2D IR and distinguished by the waiting time dependence of the cross
      peaks from the transfers between configurations of the distorted ion and solvent.
      The 2D IR analysis carried out for various polarization conditions gave frequency
      frequency auto- and cross-correlation functions for the degenerate components
      which derive from the solvent induced wagging of the -ND(2) groups of the
      guanidinium ion.

PMID- 20143801
TI  - Crucial roles of the subnanosecond local dynamics of the flap tips in the global
      conformational changes of HIV-1 protease.
AB  - To understand the underlying mechanisms of the open and closed conformational
      change of HIV-1 protease (HIV-1 PR) at multiple time scales, we performed serial
      fully unrestrained, extremely long time molecular dynamics simulations with an
      explicit solvent model. Spontaneous semiopen to closed conformational transition
      and inhibitor-collision-induced opening of the flaps were simulated in a real
      time scale. We found that the rapid, local subnanosecond fluctuations of the flap
      tips might be the mechanisms triggering the global open and close conformational
      transitions at the 100-ns time scale. The subnanosecond fluctuation is induced by
      the Phi-Psi rotations of the residues at the flap tips, mainly Psi of Gly49 and
      Phi of Ile50, disturbing the interactions between the two tips and then their
      stability. We further showed that the water molecule W301 is helpful for the
      stability of the PR-inhibitor complex by acting as a collision buffer for the
      dynamic interaction between flap tips and the inhibitor. These results might help
      gain a better insight into the dynamics of HIV-1 PR, especially the local
      dynamics of the flap tips, which may provide important guidelines for design of
      novel potent inhibitors.

PMID- 20143802
TI  - Measuring, in solution, multiple-fluorophore labeling by combining fluorescence
      correlation spectroscopy and photobleaching.
AB  - Determining the number of fluorescent entities that are coupled to a given
      molecule (DNA, protein, etc.) is a key point of numerous biological studies,
      especially those based on a single molecule approach. Reliable methods are
      important, in this context, not only to characterize the labeling process but
      also to quantify interactions, for instance within molecular complexes. We
      combined fluorescence correlation spectroscopy (FCS) and photobleaching
      experiments to measure the effective number of molecules and the molecular
      brightness as a function of the total fluorescence count rate on solutions of
      cDNA (containing a few percent of C bases labeled with Alexa Fluor 647). Here,
      photobleaching is used as a control parameter to vary the experimental outputs
      (brightness and number of molecules). Assuming a Poissonian distribution of the
      number of fluorescent labels per cDNA, the FCS-photobleaching data could be
      easily fit to yield the mean number of fluorescent labels per cDNA strand
      (approximately = 2). This number could not be determined solely on the basis of
      the cDNA brightness, because of both the statistical distribution of the number
      of fluorescent labels and their unknown brightness when incorporated in cDNA. The
      statistical distribution of the number of fluorophores labeling cDNA was
      confirmed by analyzing the photon count distribution (with the cumulant method),
      which showed clearly that the brightness of cDNA strands varies from one molecule
      to the other. We also performed complementary continuous photobleaching
      experiments and found that the photobleaching decay rate of Alexa Fluor 647 in
      the excited state decreases by about 30% when incorporated into cDNA, while its
      nonradiative decay rate is increased such that the brightness of individual Alexa
      labels is decreased by 25% compared to free Alexa dyes.

PMID- 20143803
TI  - Effect of polymer grafting on the bilayer gel to liquid-crystalline transition.
AB  - Grafted polymers on the surface of lipid membranes have potential applications in
      liposome-based drug delivery and supported membrane systems. The effect of
      polymer grafting on the phase behavior of bilayers made up of single-tail lipids
      is investigated using dissipative particle dynamics. The bilayer is maintained in
      a tensionless state using a barostat. Simulations are carried out by varying the
      grafting fraction, G(f), defined as the ratio of the number of polymer molecules
      to the number of lipid molecules, and the length of the lipid tails. At low G(f),
      the bilayer shows a sharp transition from the gel (L(beta)) to the liquid
      crystalline (L(alpha)) phase. This main melting transition temperature is lowered
      as G(f) is increased, and above a critical value of G(f), the interdigitated
      L(betaI) phase is observed prior to the main transition. The temperature range
      over which the intermediate phases are observed is a function of the lipid tail
      length and G(f). At higher grafting fractions, the presence of the L(betaI) phase
      is attributed to the increase in the area per head group due to the lateral
      pressure exerted by the polymer brush. The areal expansion and decrease in the
      melting temperatures as a function of G(f) were found to follow the scalings
      predicted by the self-consistent mean field theories for grafted polymer
      membranes. Our study shows that the grafted polymer density can be used to
      effectively control the temperature range and occurrence of a given bilayer
      phase.

PMID- 20143804
TI  - Peroxynitrite-mediated oxidative modifications of complex II: relevance in
      myocardial infarction.
AB  - Increased O(2)(*-) and NO production is a key mechanism of mitochondrial
      dysfunction in myocardial ischemia/reperfusion injury. In complex II, oxidative
      impairment and enhanced tyrosine nitration of the 70 kDa FAD-binding protein
      occur in the post-ischemic myocardium and are thought to be mediated by
      peroxynitrite (OONO(-)) in vivo [Chen, Y.-R., et al. (2008) J. Biol. Chem. 283,
      27991-28003]. To gain deeper insights into the redox protein thiols involved in
      OONO(-)-mediated oxidative post-translational modifications relevant in
      myocardial infarction, we subjected isolated myocardial complex II to in vitro
      protein nitration with OONO(-). This resulted in site-specific nitration at the
      70 kDa polypeptide and impairment of complex II-derived electron transfer
      activity. Under reducing conditions, the gel band of the 70 kDa polypeptide was
      subjected to in-gel trypsin/chymotrypsin digestion and then LC-MS/MS analysis.
      Nitration of Y(56) and Y(142) was previously reported. Further analysis revealed
      that C(267), C(476), and C(537) are involved in OONO(-)-mediated S-sulfonation.
      To identify the disulfide formation mediated by OONO(-), nitrated complex II was
      alkylated with iodoacetamide. In-gel proteolytic digestion and LC-MS/MS analysis
      were conducted under nonreducing conditions. The MS/MS data were examined with
      MassMatrix, indicating that three cysteine pairs, C(306)-C(312), C(439)-C(444),
      and C(288)-C(575), were involved in OONO(-)-mediated disulfide formation. Immuno
      spin trapping with an anti-DMPO antibody and subsequent MS was used to define
      oxidative modification with protein radical formation. An OONO(-)-dependent DMPO
      adduct was detected, and further LC-MS/MS analysis indicated C(288) and C(655)
      were involved in DMPO binding. These results offered a complete profile of OONO(
      )-mediated oxidative modifications that may be relevant in the disease model of
      myocardial infarction.

PMID- 20143805
TI  - Lung perfusion imaging with monosized biodegradable microspheres.
AB  - After intravenous injection, particles larger than red blood cells will be
      trapped in the first capillary bed that they encounter. This is the principle of
      lung perfusion imaging in nuclear medicine, where macroaggregated albumin (MAA)
      is radiolabeled with (99m)Tc, infused into a patient's arm vein, and then imaged
      with gamma scintigraphy. Our aim was to evaluate if monosized microspheres could
      replace (99m)Tc-MAA. Biodegradable poly(L-lactide) microspheres containing
      chelating bis(picolylamine) end groups were prepared by a flow focusing method on
      a microfluidic glass chip and were of highly homogeneous size (9.0 +/- 0.4
      microm). The microspheres were radiolabeled with [(99m)Tc(H(2)O)(3)(CO)(3)](+)
      and then evaluated in mice for lung perfusion imaging. Fifteen minutes after
      injection, 79.6 +/- 3.8% of the injected activity was trapped in the lungs of
      mice. Monosized biodegradable radioactive microspheres are, thus, appropriate
      lung perfusion imaging agents. Other sizes of these highly uniform microspheres
      have the potential to improve diagnostic and therapeutic approaches in diverse
      areas of medicine.

PMID- 20143806
TI  - Enhancement of oxyanion and diatrizoate reduction kinetics using selected azo
      dyes on Pd-based catalysts.
AB  - Azo dyes are widespread pollutants and potential cocontaminants for nitrate; we
      evaluated their effect on catalytic reduction of a suite of oxyanions,
      diatrizoate, and N-nitrosodimethylamine (NDMA). The azo dye methyl orange
      significantly enhanced (less than or equal to a factor of 5.24) the catalytic
      reduction kinetics of nitrate, nitrite, bromate, perchlorate, chlorate, and
      diatrizoate with several different Pd-based catalysts; NDMA reduction was not
      enhanced. Nitrate was selected as a probe contaminant, and a variety of azo dyes
      (methyl orange, methyl red, fast yellow AB, metanil yellow, acid orange 7, congo
      red, eriochrome black T, acid red 27, acid yellow 11, and acid yellow 17) were
      evaluated for their ability to enhance reduction. Hydrogenation energies of azo
      dyes were calculated using density functional theory and a volcano relationship
      between hydrogenation energies and reduction rate enhancement was observed. A
      kinetic model based on Bronsted-Evans-Polanyi (BEP) theory matched the volcano
      relationship and suggests sorbed azo dyes enhance reduction kinetics through
      hydrogen atom shuttling between reduced azo dyes (i.e., hydrazo dyes) and
      oxyanions or diatrizoate. This is the first research that has identified this
      synergetic effect, and it has implications for designing more efficient catalysts
      and reducing Pd costs in water treatment systems.

PMID- 20143807
TI  - A combined solid-state NMR and synchrotron X-ray diffraction powder study on the
      structure of the antioxidant (+)-catechin 4.5-hydrate.
AB  - Analyses combining X-ray powder diffraction (XRD) and solid-state NMR (SSNMR)
      data can now provide crystal structures in challenging powders that are
      inaccessible by traditional methods. The flavonoid catechin is an ideal candidate
      for these methods, as it has eluded crystallographic characterization despite
      extensive study. Catechin was first described nearly two centuries ago, and its
      powders exhibit numerous levels of hydration. Here, synchrotron XRD data provide
      all heavy-atom positions in (+)-catechin 4.5-hydrate and establish the space
      group as C2. SSNMR data ((13)C tensor and (1)H/(13)C correlation) complete the
      conformation by providing catechin's five OH hydrogen orientations. Since 1903,
      this phase has been erroneously identified as a 4.0 hydrate, but XRD and density
      data establish that this discrepancy is due to the facile loss of the water
      molecule located at a Wyckoff special position in the unit cell. A final
      improvement to heavy-atom positions is provided by a geometry optimization of
      bond lengths and valence angles with XRD torsion angles held constant. The
      structural enhancement in this final structure is confirmed by the significantly
      improved fit of computed (13)C tensors to experimental data.

PMID- 20143808
TI  - High-resolution spectral analysis of individual SERS-active nanoparticles in
      flow.
AB  - Nanoparticle spectroscopic tags based on surface enhanced Raman scattering (SERS)
      are playing an increasingly important role in bioassay and imaging applications.
      The ability to rapidly characterize large populations of such tags
      spectroscopically in a high-throughput flow-based platform will open new areas
      for their application and provide new tools for advancing their development. We
      demonstrate here a high-resolution spectral flow cytometer capable of acquiring
      Raman spectra of individual SERS-tags at flow rates of hundreds of particles per
      second, while maintaining the spectral resolution required to make full use of
      the detailed information encoded in the Raman signature for advanced multiplexing
      needs. The approach allows multiple optical parameters to be acquired
      simultaneously over thousands of individual nanoparticle tags. Characteristics
      such as tag size, brightness, and spectral uniformity are correlated on a per
      particle basis. The tags evaluated here display highly uniform spectral
      signatures, but with greater variability in brightness. Subpopulations in the
      SERS response, not apparent in ensemble measurements, are also shown to exist.
      Relating tag variability to synthesis parameters makes flow-based spectral
      characterization a powerful tool for advancing particle development through its
      ability to provide rapid feedback on strategies aimed at constraining desired tag
      properties. Evidence for single-tag signal saturation at high excitation power
      densities is also shown, suggesting a role for high-throughput investigation of
      fundamental properties of the SERS tags as well.

PMID- 20143809
TI  - Adsorption of beta-lactoglobulin on spherical polyelectrolyte brushes: direct
      proof of counterion release by isothermal titration calorimetry.
AB  - The thermodynamics and the driving forces of the adsorption of beta-lactoglobulin
      on spherical polyelectrolyte brushes (SPB) are investigated by isothermal
      titration calorimetry (ITC). The SPB consist of a polystyrene core onto which
      long chains of poly(styrene sulfonate) are grafted. Adsorption isotherms are
      obtained from measurements by ITC. The analysis by ITC shows clearly that the
      adsorption process is solely driven by entropy while DeltaH > 0. This finding is
      in accordance with the proposed mechanism of counterion release: Patches of
      positive charges on the surface of the proteins become multivalent counterions of
      the polyelectrolyte chains, thereby releasing the counterions of the protein and
      the polyelectrolyte. A simple statistical-mechanical model fully corroborates the
      proposed mechanism. The present analysis shows clearly the fundamental importance
      of counterion release for protein adsorption on charged interfaces and charged
      polymeric layers.

PMID- 20143810
TI  - Much of the microcin J25 leader peptide is dispensable.
AB  - The antimicrobial peptide microcin J25 (MccJ25) is matured by two enzymes, McjB
      and McjC, from a 58 amino acid (aa) preprotein, McjA, into its final 21 aa lasso
      topology. Herein we have investigated the role of the leader peptide of McjA and
      found that only the eight C-terminal amino acids of this leader peptide are
      required for maturation of MccJ25. There is a high content of lysine residues in
      the McjA leader peptide, but herein we also demonstrate that these charged amino
      acids do not play a major role in the maturation of MccJ25. Alanine scanning
      mutagenesis studies revealed that the Thr-35 residue in the leader peptide is
      critical for correct processing of McjA into mature MccJ25. In the absence of
      detailed structural and biochemical data about McjB and McjC, these studies allow
      us to propose a putative role for the leader peptide as a simple motif for
      docking of the McjA preprotein in the maturation enzymes.

PMID- 20143811
TI  - Role of Au-C interactions on the catalytic activity of au nanoparticles supported
      on TiC(001) toward molecular oxygen dissociation.
AB  - High-resolution photoemission and density functional calculations on realistic
      slab surface models were used to study the interaction and subsequent
      dissociation of O(2) with Au nanoparticles supported on TiC(001). The
      photoemission results indicate that at 150 K O(2) adsorbs molecularly on the
      supported gold nanoparticles, and upon heating to temperatures above 200 K the
      O(2) --> 2O reaction takes place with migration of atomic oxygen to the TiC(001)
      substrate. The addition of Au to TiC(001) substantially enhances the rate of O(2)
      dissociation at room temperature. The reactivity of Au nanoparticles supported on
      TiC(001) toward O(2) dissociation is much larger than that of similar
      nanoparticles supported either on TiO(2)(110) or MgO(001) surfaces, where the
      cleavage of O-O bonds is very difficult. Density functional calculations carried
      out on large supercells show that the contact of Au with TiC(001) is essential
      for charge polarization and an enhancement in the chemical activity of Au. Small
      two-dimensional particles which expose Au atoms in contact with TiC(001) are the
      most reactive. While O(2) prefers binding to Au sites, the O atoms interact more
      strongly with the TiC(001) surface. The oxygen species active during the low
      temperature (<200 K) oxidation of carbon monoxide on Au/TiC(001) is chemisorbed
      O(2). Once atomic O binds to TiC(001), the chemisorption bond is so strong that
      temperatures well above 400 K are necessary to remove the O adatoms from the
      TiC(001) substrate by direct reaction with CO. The high reactivity of Au/TiC(001)
      toward O(2) at low-temperature opens the route for the transformation of alcohols
      and amines on the supported Au nanoparticles.

PMID- 20143812
TI  - Mechanistic insights on riboflavin synthase inspired by selective binding of the
      6,7-dimethyl-8-ribityllumazine exomethylene anion.
AB  - Riboflavin synthase catalyzes the transfer of a four-carbon fragment between two
      molecules of the substrate, 6,7-dimethyl-8-ribityllumazine, resulting in the
      formation of riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione.
      Earlier, a pentacyclic adduct formed from two substrate molecules was shown to be
      a catalytically competent intermediate, but the mechanism of its formation is
      still poorly understood. The present study shows that the recombinant N-terminal
      domain of riboflavin synthase from Escherichia coli interacts specifically with
      the exomethylene-type anion of 6,7-dimethyl-8-ribityllumazine but not with any of
      the tricyclic adduct-type anions that dominate the complex anion equilibrium in
      aqueous solution. Whereas these findings can be implemented into previously
      published mechanistic hypotheses, we also present a novel, hypothetical reaction
      sequence that starts with the transfer of a hydride ion from the 6,7-dimethyl-8
      ribityllumazine exomethylene anion to an electroneutral 6,7-dimethyl-8
      ribityllumazine molecule. The pair of dehydrolumazine and dihydrolumazine
      molecules resulting from this hydride transfer is proposed to undergo a 4 + 2
      cycloaddition, affording the experimentally documented pentacyclic intermediate.
      In contrast to earlier mechanistic concepts requiring the participation of a
      nucleophilic agent, which is not supported by structural and mutagenesis data,
      the novel concept has no such requirement. Moreover, it requires fewer reaction
      steps and is consistent with all experimental data.

PMID- 20143813
TI  - Hepatic gene expression related to lower plasma cholesterol in hamsters fed high
      fat diets supplemented with blueberry peels and peel extract.
AB  - This study analyzed plasma lipid profiles, genes related to cholesterol and bile
      acid metabolism, and inflammation in liver as well as adipose tissue from Syrian
      Golden hamsters fed high-fat diets supplemented with blueberry (BB) pomace
      byproducts including 8% dried whole blueberry peels (BBPWHL), 2% dried extract of
      peels (BBPX; 95% ethanol extract), and 6% residue from extracted peel (BBPEXT)
      compared to a diet containing 5% (w/w) microcrystalline cellulose (control). All
      BB diets significantly lowered plasma very low density lipoprotein cholesterol
      and total cholesterol concentrations. Interestingly, BB diets increased fecal
      lipid excretion. Hepatic CYP7A1 expression was up-regulated by all BB diets, and
      the expression of CYP51 was up-regulated by BBPX and BBPEXT diets, suggesting
      that both bile acid and cholesterol synthesis were increased. No significant
      changes in adipocyte gene expression related to inflammatory markers were
      observed with any BB diet. These data suggest that hepatic modulation of bile
      acid and cholesterol synthesis primarily contributes to the cholesterol-lowering
      effect of BB pomace byproducts.

PMID- 20143814
TI  - Polcalcin divalent ion-binding behavior and thermal stability: comparison of Bet
      v 4, Bra n 1, and Bra n 2 to Phl p 7.
AB  - Polcalcins are pollen-specific proteins containing two EF-hands. Atypically, the
      C-terminal EF-hand binding loop in Phl p 7 (from timothy grass) harbors five,
      rather than four, anionic side chains, due to replacement of the consensus serine
      at -x by aspartate. This arrangement has been shown to heighten parvalbumin
      Ca(2+) affinity. To determine whether Phl p 7 likewise exhibits anomalous
      divalent ion affinity, we have also characterized Bra n 1 and Bra n 2 (both from
      rapeseed) and Bet v 4 (from birch tree). Relative to Phl p 7, they exhibit N
      terminal extensions of one, five, and seven residues, respectively.
      Interestingly, the divalent ion affinity of Phl p 7 is unexceptional. For
      example, at -17.84 +/- 0.13 kcal mol(-1), the overall standard free energy for
      Ca(2+) binding falls within the range observed for the other three proteins (
      17.30 +/- 0.10 to -18.15 +/- 0.10 kcal mol(-1)). In further contrast to
      parvalbumin, replacement of the -x aspartate, via the D55S mutation, actually
      increases the overall Ca(2+) affinity of Phl p 7, to -18.17 +/- 0.13 kcal mol(
      1). Ca(2+)-free Phl p 7 exhibits uncharacteristic thermal stability. Whereas wild
      type Phl p 7 and the D55S variant denature at 77.3 and 78.0 degrees C,
      respectively, the other three polcalcins unfold between 56.1 and 57.9 degrees C.
      This stability reflects a low denaturational heat capacity increment. Phl p 7 and
      Phl p 7 D55S exhibit DeltaC(p) values of 0.34 and 0.32 kcal mol(-1) K(-1),
      respectively. The corresponding values for the other three polcalcins range from
      0.66 to 0.95 kcal mol(-1) K(-1).

PMID- 20143815
TI  - Heterogeneity in polymer solar cells: local morphology and performance in organic
      photovoltaics studied with scanning probe microscopy.
AB  - The use of organic photovoltaics (OPVs) could reduce production costs for solar
      cells because these materials are solution processable and can be manufactured by
      roll-to-roll printing. The nanoscale texture, or film morphology, of the
      donor/acceptor blends used in most OPVs is a critical variable that can dominate
      both the performance of new materials being optimized in the lab and efforts to
      move from laboratory-scale to factory-scale production. Although efficiencies of
      organic solar cells have improved significantly in recent years, progress in
      morphology optimization still occurs largely by trial and error, in part because
      much of our basic understanding of how nanoscale morphology affects the
      optoelectronic properties of these heterogeneous organic semiconductor films has
      to be inferred indirectly from macroscopic measurements. In this Account, we
      review the importance of nanoscale morphology in organic semiconductors and the
      use of electrical scanning probe microscopy techniques to directly probe the
      local optoelectronic properties of OPV devices. We have observed local
      heterogeneity of electronic properties and performance in a wide range of
      systems, including model polymer-fullerene blends such as poly(3-hexylthiophene)
      (P3HT) and [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM), newer
      polyfluorene copolymer-PCBM blends, and even all polymer donor-acceptor blends.
      The observed heterogeneity in local photocurrent poses important questions,
      chiefly what information is contained and what is lost when using average values
      obtained from conventional measurements on macroscopic devices and bulk samples?
      We show that in many cases OPVs are best thought of as a collection of nanoscopic
      photodiodes connected in parallel, each with their own morphological and
      therefore electronic and optical properties. This local heterogeneity forces us
      to carefully consider the adequacy of describing OPVs solely by "average"
      properties such as the bulk carrier mobility. Characterizing this local
      heterogeneity in the morphology of an OPV and the consequent variations in local
      performance is vital to understanding OPV operation.

PMID- 20143816
TI  - The folding energy landscape and free energy excitations of cytochrome c.
AB  - The covalently bound heme cofactor plays a dominant role in the folding of
      cytochrome c. Because of the complicated inorganic chemistry of the heme, some
      might consider the folding of cytochrome c to be a special case, following
      principles different from those used to describe the folding of proteins without
      cofactors. Recent investigations, however, demonstrate that common models
      describing folding for many proteins work well for cytochrome c when heme is
      explicitly introduced, generally providing results that agree with experimental
      observations. In this Account, we first discuss results from simple native
      structure-based models. These models include attractive interactions between
      nonadjacent residues only if they are present in the crystal structure at pH 7.
      Because attractive nonnative contacts are not included in native structure-based
      models, their energy landscapes can be described as "perfectly funneled". In
      other words, native structure-based models are energetically guided towards the
      native state and contain no energetic traps that would hinder folding. Energetic
      traps are denoted sources of "frustration", which cause specific transient
      intermediates to be populated. Native structure-based models do, however, include
      repulsion between residues due to excluded volume. Nonenergetic traps can
      therefore exist if the chain, which cannot cross over itself, must partially
      unfold so that folding can proceed. The ability of native structure-based models
      to capture this kind of motion is partly responsible for their successful
      predictions of folding pathways for many types of proteins. Models without
      frustration describe the sequence of folding events for cytochrome c well (as
      inferred from hydrogen-exchange experiments), thereby justifying their use as a
      starting point. At low pH, the experimentally observed folding sequence of
      cytochrome c deviates from that at pH 7 and from models with perfectly funneled
      energy landscapes. Here, alternate folding pathways are a result of "chemical
      frustration". This frustration arises because some regions of the protein are
      destabilized more than others due to the heterogeneous distribution of titratable
      residues that are protonated at low pH. Beginning with native structure-based
      terms, we construct more complex models by adding chemical frustration. These
      more complex models only modestly perturb the energy landscape, which remains,
      overall, well funneled. These perturbed models can accurately describe how
      alternative folding pathways are used at low pH. At alkaline pH, cytochrome c
      populates distinctly different structural ensembles. For instance, lysine
      residues are deprotonated and compete for the heme ligation site. The same models
      that can describe folding at low pH also predict well the structures and relative
      stabilities of intermediates populated at alkaline pH. The success of models
      based on funneled energy landscapes suggest that cytochrome c folding is driven
      primarily by native contacts. The presence of heme appears to add chemical
      complexity to the folding process, but it does not require fundamental
      modification of the general principles used to describe folding. Moreover, its
      added complexity provides a valuable means of probing the folding energy
      landscape in greater detail than is possible with simpler systems.

PMID- 20143817
TI  - Enantioselective behavior of alpha-HCH in mouse and quail tissues.
AB  - alpha-HCH (hexachlorocyclohexane) is chiral and can still be detected in almost
      all environmental media. In this study, the enantioselective behavior of alpha
      HCH in mice (CD1) and quail (Coturnix japonica) was investigated and compared
      after a single dose of exposure. The primary nerve cell culture was conducted to
      evaluate the enantioselective metabolic capacity of nerve cells of mouse and
      quail for alpha-HCH. In various tissues of the mice and quail, the alpha-HCH
      concentrations showed a typical pattern of first-order dynamics after exposure.
      The enantiomeric fractions (EFs) in nonbrain tissues of mice decreased
      substantially, indicating continuous depletion of (+)-alpha-HCH in mice. Tissue
      specific EF trends in quail and enantioselective degradation of (-)-alpha-HCH in
      quail liver were observed. These observations indicated that the dynamic changes
      of EFs in mice and quail were independent of concentration changes in the same
      tissues. In brain tissues, the enantioenrichment of (+)-enantiomer was totally
      independent of their concentrations in blood. The in vitro metabolism of alpha
      HCH in the primary nerve cells were negligible, and the slight EF changes in
      primary nerve cells demonstrated that metabolism, uptake, and excretion in the
      brain cells would not lead to the observed dramatic enantioenrichment of (+)
      alpha-HCH in the brain tissues of the two animals. The enantioselective transport
      across the blood-brain barrier was the primary cause for the enantioenrichment of
      (+)-alpha-HCH in the brain tissues.

PMID- 20143818
TI  - Zn and Cu isotopes as tracers of anthropogenic contamination in a sediment core
      from an urban lake.
AB  - In this work, we use stable Zn and Cu isotopes to identify the sources and timing
      of the deposition of these metals in a sediment core from Lake Ballinger near
      Seattle, Washington, USA. The base of the Lake Ballinger core predates settlement
      in the region, while the upper sections record the effects of atmospheric
      emissions from a nearby smelter and rapid urbanization of the watershed.
      delta(66)Zn and delta(65)Cu varied by 0.50 per thousand and 0.29 per thousand,
      respectively, over the 500 year core record. Isotopic changes were correlated
      with the presmelter period ( approximately 1450 to 1900 with delta(66)Zn = +0.39
      per thousand +/- 0.09 per thousand and delta(65)Cu = +0.77 per thousand +/- 0.06
      per thousand), period of smelter operation (1900 to 1985 with delta(66)Zn = +0.14
      +/- 0.06 per thousand and delta(65)Cu = +0.94 +/- 0.10 per thousand), and
      postsmelting/stable urban land use period (post 1985 with delta(66)Zn = 0.00 +/-
      0.10 per thousand and delta(65)Cu = +0.82 per thousand +/- 0.12 per thousand).
      Rapid early urbanization during the post World War II era increased metal loading
      to the lake but did not significantly alter the delta(66)Zn and delta(65)Cu,
      suggesting that increased metal loads during this time were derived mainly from
      mobilization of historically contaminated soils. Urban sources of Cu and Zn were
      dominant since the smelter closed in the 1980s, and the delta(66)Zn measured in
      tire samples suggests tire wear is a likely source of Zn.

PMID- 20143819
TI  - Evaluation of the uncertainties caused by the forward scattering in turbidity
      measurement of the coagulation rate.
AB  - The forward scattering light (FSL) received by the detector can cause
      uncertainties in turbidity measurement of the coagulation rate of colloidal
      dispersion, and this effect becomes more significant for large particles. In this
      study, the effect of FSL is investigated on the basis of calculations using the T
      matrix method, an exact technique for the computation of nonspherical scattering.
      The theoretical formulation and relevant numerical implementation for predicting
      the contribution of FSL in the turbidity measurement is presented. To
      quantitatively estimate the degree of the influence of FSL, an influence ratio
      comparing the contribution of FSL to the pure transmitted light in the turbidity
      measurement is introduced. The influence ratios evaluated under various
      parametric conditions and the relevant analyses provide a guideline for properly
      choosing particle size, measuring wavelength to minimize the effect of FSL in
      turbidity measurement of coagulation rate.

PMID- 20143820
TI  - Tissue distribution and maternal transfer of poly- and perfluorinated compounds
      in Chinese sturgeon (Acipenser sinensis): implications for reproductive risk.
AB  - It is critical to investigate the tissue distribution and maternal transfer of
      poly- and perfluorinated compounds (PFCs) in wild fish for assessing potential
      effects on ecosystems. Concentrations of 23 PFCs in nine organs and egg were
      measured in 16 17- to 25-year-old female Chinese sturgeon (Acipenser sinensis, an
      anadromous fish), that died during propagation. Three polyfluorinated amides were
      detected in stomach, intestine, and gills and 7:3 FTCA was specifically
      accumulated in liver. The greatest total concentration of PFCs in egg was 35.1 +/
      10.4 ng/g ww and was predominated by perfluorooctane sulfonate (PFOS) and
      perfluorotridecanoate acid (PFTriDA). The longer-chain C(11)-C(14) and C(16)
      perfluorinated carboxylates were more accumulated in Chinese sturgeon than PFOS,
      partly due to the increasing trends of PFCAs with fish age. Maternal transfer
      ratios of PFCs expressed as ratios of concentrations in the egg to those in the
      liver ranged from 0.79 (perfluorooctanoate) to 5.5 (PFTriDA), depending on their
      carbon chain lengths or protein-water coefficients. The PFOS equivalent of PFC
      mixtures, calculated by multiplying the relative potency factor of each PFC to
      PFOS by the corresponding concentration, ranged from 90.6 to 262 ng/g. The hazard
      quotient was 0.20, implying potential reproductive effects of PFCs on Chinese
      sturgeon.

PMID- 20143821
TI  - Design and application of an inertial impactor in combination with an ATP
      bioluminescence detector for in situ rapid estimation of the efficacies of air
      controlling devices on removal of bioaerosols.
AB  - We proposed a rapid method to estimate the efficacies of air controlling devices
      in situ using ATP bioluminescence in combination with an inertial impactor. The
      inertial impactor was designed to have 1 mum of cutoff diameter, and its
      performance was estimated analytically, numerically, and experimentally. The
      proposed method was characterized using Staphylococcus epidermidis, which was
      aerosolized with a nebulizer. The bioaerosol concentrations were estimated within
      25 min using the proposed method without a culturing process, which requires
      several days for colony formation. A linear relationship was obtained between the
      results of the proposed ATP method (RLU/m(3)) and the conventional culture-based
      method (CFU/m(3)), with R(2) 0.9283. The proposed method was applied to estimate
      the concentration of indoor bioaerosols, which were identified as a mixture of
      various microbial species including bacteria, fungi, and actinomycetes, in an
      occupational indoor environment, controlled by mechanical ventilation and an air
      cleaner. Consequently, the proposed method showed a linearity with the culture
      based method for indoor bioaerosols with R(2) 0.8189, even though various kinds
      of microorganisms existed in the indoor air. The proposed method may be effective
      in monitoring the changes of relative concentration of indoor bioaerosols and
      estimating the effectiveness of air control devices in indoor environments.

PMID- 20143822
TI  - Total synthesis of (-)-muraymycin D2 and its epimer.
AB  - Full details of the first total synthesis of (-)-muraymycin (MRY) D2 and its
      epimer, the antibacterial nucleoside natural product, are described. Key
      strategic elements of the approach include the preparation of the urea dipeptide
      moiety found in the muraymycins containing an L-epi-capreomycidine via a nitrene
      C-H insertion of the sulfamate 10 and the fully protected muraymycin skeleton at
      a late stage by an Ugi four-component reaction. Thus, the nitrene C-H insertion
      of the sulfamate 10 with 10 mol % of Rh(2)(esp)(2) catalyst gave the cyclic
      sulfamates 11a and 11b in 47% yield (11a:11b = 1:2.0). Construction of the cyclic
      guanidine skeleton was effected through the HgBr(2)-promoted cyclization of 42
      followed by desulfonylation upon acetolysis of the oxathiazinane ring to give 43
      in good yield. The amine obtained by selective removal of the Cbz group of the
      alcohol 44 was reacted with MeSC(=O)-L-Val-O-t-Bu (38) to provide 45, which was
      oxidized to the carboxylic acid 46. Reaction of 46, isonitrile 51,
      isovaleraldehyde, and 2,4-dimethoxybenzylamine furnished the desired Ugi
      products, the final deprotection of which successfully afforded (-)-MRY D2 and
      epi-MRY D2 (53) after HPLC separation of the diastereomers. This approach would
      afford ready access to a range of analogues simply by altering each component.

PMID- 20143823
TI  - Accelerating dewetting on deformable substrates by adding a liquid underlayer.
AB  - We investigated the dependence of the dewetting velocity of a thin, low-viscosity
      polystyrene (PS) top film on a poly(methyl methacrylate) (PMMA) double layer
      consisting of a low-viscosity underlayer of thickness h(L) coated with a high
      viscosity middle layer of thickness h(M). The addition of the liquid underlayer
      generated complex nonmonotonic behavior of the dewetting velocity as a function
      of increasing h(M). In particular, we observed an acceleration of dewetting for
      an intermediate range of h(M). This phenomenon has been interpreted by a
      combination deformation of the middle elastic layer and a concurrent change in
      the contact angle. On one hand, deformation led to the formation of a trench that
      dissipated energy during its movement through the liquid underlayer and thus
      caused a slowing down of dewetting. However, with an increase in the thickness of
      the elastic middle layer, the size of the trench decreased and its influence on
      the dewetting velocity also decreased. On the other hand, the deformation of the
      elastic layer also led to an increase in the contact angle. This increase in the
      driving capillary forces caused an increase in the dewetting velocity.

PMID- 20143824
TI  - Effect of anthocyanin-rich extract from black rice (Oryza sativa L. Japonica) on
      chronically alcohol-induced liver damage in rats.
AB  - The study evaluated the protective effect of anthocyanin-rich extract from black
      rice (AEBR) on chronic ethanol-induced biochemical changes in male Wistar rats.
      Administration of ethanol (3.7 g/kg/day) to Wistar rats for 45 days induced liver
      damage with a significant increase (P < 0.05) of aspartate transaminase (AST),
      alanine transaminase (ALT), gamma glutamyl transferase (GGT) in the serum and the
      hepatic malondialdehyde (MDA) level. In contrast, administration of AEBR (500
      mg/kg) along with alcohol significantly (P < 0.01) decreased the activities of
      liver enzymes (AST, ALT and GGT) in serum, the MDA levels and the concentrations
      of serum and hepatic triglyceride (TG) and total cholesterol (TCH). Rats treated
      with AEBR showed a better profile of the antioxidant system with normal
      glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione S
      transferase (GST) activities. All these results were accompanied by histological
      observations in liver. The results demonstrate that AEBR has a beneficial effect
      in reducing the adverse effect of alcohol.

PMID- 20143825
TI  - Chemoenzymatic synthesis of alpha-hydroxy-beta-methyl-gamma-hydroxy esters: role
      of the keto-enol equilibrium to control the stereoselective hydrogenation in a
      key step.
AB  - Alpha-hydroxy-beta-methyl-gamma-hydroxy esters not only are found in many natural
      products and potent drugs but also are useful intermediates in organic synthesis
      due to their highly functionalized skeleton that can be further manipulated and
      applied in the synthesis of many compounds with remarkable biological activities.
      This work was based on a chemoenzymatic approach to obtain these molecules with
      three contiguous stereogenic centers in a highly enantio- and diastereoselective
      way. Two distinct linear routes were proposed in which the key steps in both
      routes consisted of initial stereocontrolled ketoester bioreduction followed by
      unsaturated carbonyl bioreduction or reduction with Pd-C. Other key reactions in
      the synthesis include a Wasserman protocol for chain homologation and a Mannich
      type olefination with maintenance of enantiomeric excess for all intermediates
      during the sequence. Whereas route A gave exclusively the skeleton with 3R,4R,5S
      configuration (99% ee and 11.5% global yield after 7 steps), route B gave the
      skeleton with 3R,4R,5S and 3R,4S,5R configurations (dr 1:12, 98% ee and 20%
      global yield after 5 steps).

PMID- 20143826
TI  - Adsorption of CO(2), CH(4), N(2)O, and N(2) on MOF-5, MOF-177, and zeolite 5A.
AB  - Adsorption equilibrium and kinetics of CO(2), CH(4), N(2)O, and N(2) on two newly
      discovered adsorbents, metal-organic frameworks MOF-5 and MOF-177 and one
      traditional adsorbent, zeolite 5A were determined to assess their efficacy for
      CO(2), CH(4), and N(2)O removal from air and separation of CO(2) from CH(4) in
      pressure swing adsorption processes. Adsorption equilibrium and kinetics data for
      CO(2), CH(4), N(2)O, and N(2) on all three adsorbents were measured
      volumetrically at 298K and gas pressures up to 800 Torr. Adsorption equilibrium
      capacities of CO(2) and CH(4) on all three adsorbents were determined
      gravimetrically at 298 K and elevated pressures (14 bar for CO(2) and 100 bar for
      CH(4)). The Henry's law and Langmuir adsorption equilibrium models were applied
      to correlate the adsorption isotherms, and a classical micropore diffusion model
      was used to analyze the adsorption kinetic data. The adsorption equilibrium
      selectivity was calculated from the ratio of Henry's constants, and the adsorbent
      selection parameter for pressure swing adsorption processes were determined by
      combining the equilibrium selectivity and working capacity ratio. Based on the
      selectivity and adsorbent selection parameter results, zeolite 5A is a better
      adsorbent for removing CO(2) and N(2)O from air and separation of CO(2) from
      CH(4), whereas MOF-177 is the adsorbent of choice for removing CH(4) from air.
      However, both MOF adsorbents have larger adsorption capacities for CO(2) and
      CH(4) than zeolite 5A at elevated pressures, suggesting MOF-5 and MOF-177 are
      better adsorbents for CO(2) and CH(4) storage. The CH(4) adsorption capacity of
      22 wt.% on MOF-177 at 298K and 100 bar is probably the largest adsorption uptake
      of CH(4) on any dry adsorbents. The average diffusivity of CO(2), CH(4) and N(2)O
      in MOF-5 and MOF-177 is in the order of 10(-9) m(2)/s, as compared to 10(-11)
      m(2)/s for CO(2), CH(4) and N(2)O in zeolite 5A. The effects of gas pressure on
      diffusivity for different adsorabte-adsorbent systems were also investigated.

PMID- 20143827
TI  - Monitoring the 3D nanostructures of bulk heterojunction polymer solar cells using
      confocal lifetime imaging.
AB  - In this study, the exciton lifetime images within the photoactive layers of
      poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester
      (PCBM) are revealed by confocal optical microscopy combined with the fluorescence
      module. The images reveal that the active layers during slow solvent evaporation
      provide 3D pathways for charge transport and the concentration gradient through
      the film which reflects the better cell performance. This technique offers a
      great help to investigate the 3D optical-physical property without destroying the
      blends.

PMID- 20143828
TI  - On the anomalous decomposition and reactivity of ammonium and potassium
      dinitramide.
AB  - Mechanistic pathways for the thermal decomposition of the solid-state energetic
      oxidizers ammonium dinitramide (ADN) and potassium dinitramide (KDN) have been
      deciphered by carefully considering previously performed experimental studies and
      using state of the art quantum chemical modeling of molecular clusters.
      Decomposition is governed by surface chemical processes, involving polarized
      (twisted) dinitramide anions of reduced stability. Under atmospheric and low
      pressure conditions, the rate-determining step for the decomposition of these
      dinitramide salts is the dissociation into NO(2) and NNO(2)(-) radicals. The
      activation barriers for these steps are estimated to be 30 and 36 kcal/mol for
      ADN and KDN, respectively. The known stabilizing effect of water is explained by
      its hydrogen bonding ability, which counteracts polarization of surface
      dinitramides. The reactivity of ADN toward various chemical environments is
      likely explained through metastable decomposition radical intermediates. Donation
      of hydrogen bonds, antioxidant character, and basicity are properties believed to
      correlate with a compound's ability to act as a stabilizer for dinitramide salts.

PMID- 20143829
TI  - Simultaneous detection of two analytes using a spectroelectrochemical sensor.
AB  - Spectroelectrochemical sensors developed in our group achieve three modes of
      selectivity by combining electrochemistry, spectroscopy, and a chemically
      selective membrane in a single device. Analyte detection is based upon a change
      in the optical response due to the conversion of the analyte between two
      oxidation states that results from the cycling or stepping of the applied
      potential. We have demonstrated a novel approach to simultaneously detect two
      metals by combining optical stripping voltammetry for one metal (Pb(2+)) and the
      in situ ligand complexation in a film for the other metal (Fe(2+)). Using an
      indium tin oxide (ITO) sensor platform with a 50 nm Nafion film to preconcentrate
      the analytes, equimolar mixtures of Pb(2+) and Fe(2+) in 0.1 M sodium acetate
      buffer (pH 5) were detected. Pb(2+) was detected by optical stripping
      voltammetry, in which lead was deposited as metal on the ITO and detected by the
      optical change as it was removed by stripping. The ferrous ion was detected by
      the in situ ligand complexation method in which Fe(2+) was complexed with 2,2'
      bipyridyl in the Nafion in the film to form an intense red complex that was
      detected by absorbance at 520 nm. Detection limits of 300 and 400 nM were
      obtained for Pb(2+) and Fe(2+), respectively. The presence of the film had no
      effect on the optical signal that results from the deposition and stripping of
      the Pb(2+). In addition, competition between the Pb(2+) and Fe(2+) for sites in
      the film and for the organic ligand was investigated.

PMID- 20143830
TI  - A statistically rigorous test for the identification of parent-fragment pairs in
      LC-MS datasets.
AB  - Untargeted global metabolic profiling by liquid chromatography-mass spectrometry
      generates numerous signals that are due to unknown compounds and whose
      identification forms an important challenge. The analysis of metabolite
      fragmentation patterns, following collision-induced dissociation, provides a
      valuable tool for identification, but can be severely impeded by close
      chromatographic coelution of distinct metabolites. We propose a new algorithm for
      identifying related parent-fragment pairs and for distinguishing these from
      signals due to unrelated compounds. Unlike existing methods, our approach
      addresses the problem by means of a hypothesis test that is based on the
      distribution of the recorded ion counts, and thereby provides a statistically
      rigorous measure of the uncertainty involved in the classification problem.
      Because of technological constraints, the test is of primary use at low and
      intermediate ion counts, above which detector saturation causes substantial bias
      to the recorded ion count. The validity of the test is demonstrated through its
      application to pairs of coeluting isotopologues and to known parent-fragment
      pairs, which results in test statistics consistent with the null distribution.
      The performance of the test is compared with a commonly used Pearson correlation
      approach and found to be considerably better (e.g., false positive rate of 6.25%,
      compared with a value of 50% for the correlation for perfectly coeluting ions).
      Because the algorithm may be used for the analysis of high-mass compounds in
      addition to metabolic data, we expect it to facilitate the analysis of
      fragmentation patterns for a wide range of analytical problems.

PMID- 20143831
TI  - Density functional theory for adsorption of gas mixtures in metal-organic
      frameworks.
AB  - In this work, a recently developed density functional theory in three-dimensional
      space was extended to the adsorption of gas mixtures. Weighted density
      approximations to the excess free energy with different weighting functions were
      adopted for both repulsive and attractive contributions. An equation of state for
      hard-sphere mixtures and a modified Benedict-Webb-Rubin equation for Lennard
      Jones mixtures were used to estimate the excess free energy of a uniform fluid.
      The theory was applied to the adsorption of CO(2)/CH(4) and CO(2)/N(2) mixtures
      in two metal-organic frameworks: ZIF-8 and Zn(2)(BDC)(2)(ted). To validate the
      theoretical predictions, grand canonical Monte Carlo simulations were also
      conducted. The predicted adsorption and selectivity from DFT were found to agree
      well with the simulation results. CO(2) has stronger adsorption than CH(4) and
      N(2), particularly in Zn(2)(BDC)(2)(ted). The selectivity of CO(2) over CH(4) or
      N(2) increases with increasing pressure as attributed to the cooperative
      interactions of adsorbed CO(2) molecules. The composition of the gas mixture
      exhibits a significant effect on adsorption but not on selectivity.

PMID- 20143832
TI  - Potent method for the simultaneous determination of glutathione and hydrogen
      peroxide in mitochondrial compartments of apoptotic cells with microchip
      electrophoresis-laser induced fluorescence.
AB  - The first application of microchip electrophoresis with laser-induced
      fluorescence (MCE-LIF) detection to simultaneously determine glutathione (GSH)
      and hydrogen peroxide (H(2)O(2)) in mitochondria was described. Organoselenium
      probe Rh-Se-2 and bis(p-methylbenzenesulfonate)dichlorofluorescein (FS)
      synthesized in our laboratory were utilized as fluorescent probes for GSH and
      H(2)O(2), respectively. Rh-Se-2, which is nonfluorescent, reacts with GSH to
      produce rhodamine 110 (Rh110) with high quantum yield. Similarly, nonfluorescent
      FS reacts with H(2)O(2) and produces dichlorofluorescein (DCF) accompanied by
      drastic fluorescence enhancement. Both probes exhibit good sensitivity toward
      their respective target molecule determination. Fast, simple, and sensitive
      determination of GSH and H(2)O(2) was realized within 37 s using a running buffer
      of 50 mM mannitol, 40 mM HEPES (pH 7.4), and an electric field of 360 V/cm for
      separation. The linear ranges of the method were 3.3 x 10(-9)-1.0 x 10(-7) M/2.9
      x 10(-7)-1.0 x 10(-4) M and 2.7 x 10(-9)-4.0 x 10(-7) M with detection limits
      (signal-to-noise ratio = 3) of 1.3 nM (0.16 amol) and 1.0 nM (0.12 amol) for GSH
      and H(2)O(2), respectively. The relative standard deviations (RSDs) of migration
      time and peak area were less than 1.0% and 4.0%, respectively. The MCE-LIF assay
      was utilized to investigate the levels of GSH and H(2)O(2) in mitochondria
      isolated from HepG2 cells and were found to be 2.01 +/- 0.21 mM and 5.36 +/- 0.45
      microM, respectively. The method was further extended to observe situations of
      the two species in mitochondria of HepG2 cells experiencing cell apoptosis that
      were induced by doxorubicin and photodynamic therapy (PDT).

PMID- 20143833
TI  - Canonical variational transition-state theory study of the CF3CHFCH2F + OH
      reaction.
AB  - Variational transition-state theory rate constants with multidimensional
      tunneling contributions using the small curvature method have been calculated for
      the CF(3)CHFCH(2)F (HFC-245eb) + OH reaction over a temperature range from 200 to
      800 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 CH(3)F + OH reaction, has been used in conjunction with the 6
      31+G(d,p) basis set to explore the potential energy surface of the title
      reaction. The functional provides results within the limits of chemical accuracy,
      supporting the conclusions about transferability of a previous study on the
      CF(3)CH(2)CH(3) + OH reaction. Fourteen different reaction channels have been
      explored, all of them with significant contributions to the global rate
      constants.

PMID- 20143834
TI  - Discrimination of chiral solids: a terahertz spectroscopic investigation of L-
      and DL-serine.
AB  - The terahertz (THz, far-infrared) spectra of enantiomerically pure and racemic
      crystalline serine were investigated using time-domain THz spectroscopy and solid
      state density functional theory (DFT) in the spectral range of 10-90 cm(-1). The
      experimental THz spectra of L- and DL-serine at 78 K appear quite similar despite
      the significant differences in arrangement of the molecules in their crystal
      structures. Structural analyses of the two systems and calculation of the
      vibrational modes and intensities were performed using DFT with periodic boundary
      conditions employing the B3LYP and PW91 density functionals with the 6-31G(d,p)
      and 6-311G(d,p) basis sets. The applied computational methods produced
      simulations of the THz spectra in good agreement with experiment, with accurate
      predictions of the subtle differences in the THz spectra of the two chiral solid
      state mixtures of serine. The observed spectral features are assigned as
      primarily external lattice translations and rotations with lesser contributions
      due to intramolecular torsions of the -NH(3)(+) and -COO(-) groups modified by
      intermolecular hydrogen bonding.

PMID- 20143835
TI  - Drop-on-demand patterning of bacterial cells using pulsed jet electrospraying.
AB  - In this study, the drop-on-demand patterning of bacterial cells on a raw silicon
      wafer was newly conducted with an electrospray pulsed jet. We produced various
      sized line patterns and spot patterns of bacterial cells on the silicon wafer
      under varying experimental conditions of frequency, flow rate, and translational
      speed of the electrospray system in one and two-dimensional ways. Especially, the
      electrospray's pulsed jet of bacterial solution produced regular patterns of
      around 10 microm diameter spots, each of which contained a single bacterial cell.
      By enabling drop-on-demand patterning and manipulation of single bacterial cells
      on a raw wafer in the gas phase, this new technique broadens the scope of
      biological experiments beyond liquid phase treatments to solid and gas-phase
      treatments.

PMID- 20143836
TI  - Small and reproducible isotope effects during methylation with trimethylsulfonium
      hydroxide (TMSH): a convenient derivatization method for isotope analysis of
      negatively charged molecules.
AB  - Negatively charged analytes must be derivatized prior to gas chromatography
      isotope ratio mass spectrometry (GC-IRMS), with stringent control of isotope
      fractionation. Current methods require offline sample preparation. This study
      tests for the first time trimethylsulfonium hydroxide (TMSH) as online
      methylation agent prior to isotope analysis, addressing the herbicides bentazone
      and MCPA. Fully automated derivatization was achieved in a temperature
      programmable GC injector, where reactants were injected into a packed liner,
      solvents were removed by split flow, and subsequent flash heating triggered the
      derivatization, thereby transferring derivatives onto the chromatographic column.
      Stoichiometric addition of TMSH resulted in complete conversion giving accurate
      and reproducible nitrogen isotope values of bentazone. In contrast, reproducible
      carbon isotope analysis required TMSH in > or = 250-fold excess. Contrary to
      expectations, delta(13)C values became more negative at smaller TMSH excess. This
      indicates that elevated methyl group concentrations in the pore space of the
      injection liner facilitated close-to-equilibrium rather than kinetic isotope
      fractionation resulting in reproducible derivatization conditions. delta(13)C
      results under these conditions compared favorably with liquid chromatography
      IRMS: low standard deviations (0.3 per thousand for GC-IRMS, 0.1 per thousand for
      LC-IRMS) and a comparable offset of 1 per thousand compared to elemental analyzer
      IRMS demonstrate that both methods represent expedient ways for online isotope
      analysis of anionic target compounds.

PMID- 20143837
TI  - Focused microwave-induced combustion: a new technique for sample digestion.
AB  - A procedure for sample digestion based on focused microwave-induced combustion
      (FMIC) is proposed. This system was developed using a commercial focused
      microwave oven with a lab-made quartz sample holder and a modified glass vessel.
      Oxygen flow was used to start and support the combustion. A botanical sample was
      used to evaluate the operational conditions for further Al, Ba, Ca, Fe, Mg, Mn,
      Sr, and Zn determination by inductively coupled plasma optical emission
      spectrometry. Pelletized samples were positioned on the quartz holder, and 50
      microL of 6 mol L(-1) NH(4)NO(3) solution was added as igniter. Combustion was
      completed in less than 2 min, and the temperature was higher than 950 degrees C.
      The use of a reflux step, the position of sample holder inside the vessel, sample
      mass, ignition and combustion time, oxygen flow rate, and condenser type were
      evaluated. Results were compared with those obtained by focused microwave
      assisted wet digestion and by high pressure microwave-assisted wet digestion.
      Agreement of 95-103% was obtained for certified reference materials digested by
      FMIC (reflux step with 10 mL of 4 mol L(-1) HNO(3)). With the proposed procedure,
      a complete sample decomposition (residual carbon content lower than 0.5%) was
      achieved with low consumption of reagents as only 10 mL of diluted nitric acid
      was necessary. Low relative standard deviation (lower than 3.8%) was observed and
      high amount of sample (up to 1500 mg) could be digested that allowed lower limits
      of detection.

PMID- 20143838
TI  - Discrimination of complex mixtures by a colorimetric sensor array: coffee aromas.
AB  - The analysis of complex mixtures presents a difficult challenge even for modern
      analytical techniques, and the ability to discriminate among closely similar such
      mixtures often remains problematic. Coffee provides a readily available archetype
      of such highly multicomponent systems. The use of a low-cost, sensitive
      colorimetric sensor array for the detection and identification of coffee aromas
      is reported. The color changes of the sensor array were used as a digital
      representation of the array response and analyzed with standard statistical
      methods, including principal component analysis (PCA) and hierarchical clustering
      analysis (HCA). PCA revealed that the sensor array has exceptionally high
      dimensionality with 18 dimensions required to define 90% of the total variance.
      In quintuplicate runs of 10 commercial coffees and controls, no confusions or
      errors in classification by HCA were observed in 55 trials. In addition, the
      effects of temperature and time in the roasting of green coffee beans were
      readily observed and distinguishable with a resolution better than 10 degrees C
      and 5 min, respectively. Colorimetric sensor arrays demonstrate excellent
      potential for complex systems analysis in real-world applications and provide a
      novel method for discrimination among closely similar complex mixtures.

PMID- 20143839
TI  - Interchain interactions in organic conjugated dimers: a composite-molecule
      approach.
AB  - A theoretical composite-molecule (CM) model is adopted for evaluating the
      electronic excited states and excitonic couplings of cofacial conjugated dimers
      where the contributions of charge-transfer (CT) exciton, unavailable by the
      commonly used supermolecular approach due to the inadequate basis set
      construction, can be unambiguously identified within this methodology. This
      method builds up with the basis set of individual molecules and then constructs
      combined electronic states for the dimer by considering intermolecular
      interactions including charge-transfer interactions. The dependences of the
      matrix elements on intermolecular distance and conjugation length are examined.
      At the short distance region between two of the polyene molecules in the dimer,
      the CT transitions are apparently mixing to both first and second excited states.
      Also, some of the matrix elements for the mixing of CT transitions with local
      transitions which related to the second excited state are found to be
      considerably larger than the exciton-type elements. An interesting finding is
      that with increasing the chain size the CT contribution to the second excited
      state reveals a minimum and indicates HOMO to LUMO charge transfer is not the
      major CT contribution to the second excited state in the face-to-face polyene
      dimer with larger chain size and interchain separation in the region of 3.6-4.0
      A. A detail analysis reveals that HOMO-1 to LUMO and HOMO to LUMO+1 charge
      transfers are major CT contributions to the second excited state in the condition
      under study.

PMID- 20143840
TI  - Biological and biophysical properties of the histone deacetylase inhibitor
      suberoylanilide hydroxamic acid are affected by the presence of short alkyl
      groups on the phenyl ring.
AB  - Inhibition of histone deacetylases (HDACs) leads to growth arrest,
      differentiation, or apoptosis of tumor cell lines, suggesting HDACs as promising
      targets for cancer therapy. At present, only one HDAC inhibitor (HDACi) is used
      in therapy: suberoylanilide hydroxamic acid (SAHA). Here, we describe the
      synthesis and biological evaluation of a new series of compounds derived from
      SAHA by substituting short alkyl chains at various positions of the phenyl ring.
      Such modifications induced variable effects ranging from partial loss of activity
      to increased potency. Through molecular modeling, we describe a possible
      interaction between HDAC7 proline 809, a residue that is strictly conserved
      within class 2 enzymes only, and the amide group of HDACi, while nuclear magnetic
      resonance experiments indicated that dimethyl m-substitution may stabilize the
      inhibitor in the active site. Our data provide novel information on the structure
      activity relationship of HDACi and suggest new ways for developing second
      generation SAHA-like molecules.

PMID- 20143841
TI  - Major difference between the isoelectronic fluoroborylene and carbonyl ligands:
      triply bridging fluoroborylene ligands in Fe3(BF)3(CO)9 isoelectronic with
      Fe3(CO)12.
AB  - The structure of Fe(3)(BF)(3)(CO)(9) is predicted to be very different than that
      of any of the isoelectronic homoleptic M(3)(CO)(12) derivatives (M = Fe, Ru, Os).
      Thus the lowest energy Fe(3)(BF)(3)(CO)(9) structure by approximately 19 kcal/mol
      has mu(3)-BF groups bridging the top and bottom of the Fe(3) triangle with a
      third edge-bridging BF group in addition to nine terminal carbonyl groups. No
      analogous M(3)(CO)(12) structures are found with mu(3)-CO groups bridging the
      M(3) triangle. Higher energy Fe(3)(BF)(3)(CO)(9) structures with two edge
      bridging mu-BF groups and one terminal BF group are also found, analogous to the
      experimentally known Fe(3)(CO)(12) structure. However, these structures are
      transition states leading to local minima with one unsymmetrical face-bridging
      mu(3)-BF group, one edge-bridging mu-BF group, and one terminal BF group. No
      Fe(3)(BF)(3)(CO)(9) structures are found with exclusively terminal BF and CO
      groups analogous to the known structures of M(3)(CO)(12) (M = Ru, Os). These
      studies suggest that the BF group has a significantly greater tendency than the
      CO group to bridge two or three metal atoms, probably owing to the reluctance of
      the fluorine of the BF ligands to be a part of a formal double or triple bond.

PMID- 20143842
TI  - Iron-catalyzed regio- and stereoselective substitution of gamma,delta-epoxy
      alpha,beta-unsaturated esters and amides with Grignard reagents.
AB  - When gamma,delta-epoxy-alpha,beta-unsaturated esters or amides were treated with
      2 equiv of Grignard reagents in the presence of 10-24 mol % FeCl(2), regio- and
      stereoselective substitution of the epoxide moiety with the Grignard reagent
      occurred to give exclusively delta-hydroxy-gamma-alkyl or aryl-alpha,beta
      unsaturated esters or amides in good yields.

PMID- 20143843
TI  - Gold(I)-catalyzed highly regio- and stereoselective decarboxylative amination of
      allylic N-tosylcarbamates via base-induced aza-Claisen rearrangement in water.
AB  - A gold(I)-catalyzed decarboxylative amination of allylic N-tosylcarbamates via
      base-induced aza-Claisen rearrangement has been developed. A variety of
      substituted N-tosyl allylic amines were obtained in good yield, excellent
      regioselectivity, and high to excellent stereoselectivity. This transformation
      could be performed either in H(2)O or in one pot directly from allylic alcohols
      and therefore represents an efficient and environmentally benign protocol for the
      synthesis of N-tosyl allylic amines.

PMID- 20143844
TI  - Remarkable effects of P-perfluorophenyl group on the synthesis of core-modified
      phosphaporphyrinoids and phosphadithiasapphyrin.
AB  - P,X,N(2)-type phosphaporphyrins and phosphacalixphyrins (X = N, S) bearing a
      perfluorophenyl (C(6)F(5)) group at the core phosphorus atom were prepared in
      high overall yield from 1-perfluorophenyl-2,5-di(ethoxycarbonyl)phosphole as a
      common starting material. In addition, P-C(6)F(5) P,S(2),N(2)-type sapphyrin was
      successfully prepared as the first example of ring-expanded phosphorus-containing
      porphyrin.

PMID- 20143845
TI  - Enantioselective Friedel-Crafts reaction of beta-trifluoromethylated acrylates
      with pyrroles and its application to the synthesis of trifluorinated
      heliotridane.
AB  - The first chiral Lewis acid catalyzed enantioselective Friedel-Crafts alkylation
      of pyrroles with beta-CF(3) acrylates has been investigated, which afforded
      various types of chiral trifluoromethylated compounds in excellent yields (90
      99%) with high ee's (up to 99% ee). With the aid of the Friedel-Crafts reaction
      adduct, optically active trifluorinated heliotridane was successfully
      constructed.

PMID- 20143846
TI  - A facile and mild synthesis of enamides using a gold-catalyzed nucleophilic
      addition to allenamides.
AB  - A mild and facile synthesis of enamides has been developed, based on nucleophilic
      addition of electron-rich aromatic and heteroaromatics to an allenamide unit
      catalyzed by a gold salt. Yields for the transformation were 29-98%.

PMID- 20143847
TI  - Synthesis of aryl-substituted bis(imino)pyridine iron dinitrogen complexes.
AB  - The synthesis and characterization of dimeric, aryl-substituted
      bis(imino)pyridine iron dinitrogen complexes is described. In contrast to
      reduction with sodium amalgam where bis(chelate) iron compounds were isolated,
      stirring ((Ar)PDI)FeBr(2) or ((Me)BPDI)FeBr(2) (PDI = 2,6-(ArN=CMe)(2)C(5)H(3)N;
      Ar = 2,6-Et(2)-C(6)H(3)N ((Et)PDI), 2,6-Me(2)-C(6)H(3)N ((Me)PDI), 2-(i)Pr,6-Me
      C(6)H(3)N ((Me,iPr)PDI); (Me)BPDI = 2,6-(2,6-Me(2)-C(6)H(3)N=CPh)(2)C(5)H(3)N)
      with sodium naphthalenide resulted in isolation of the desired iron dinitrogen
      compounds as diamagnetic solids. Two examples, [((Et)PDI)Fe(N(2))](2)(mu(2)-N(2))
      and [((Me)BPDI)Fe(N(2))](2)(mu(2)-N(2)), were characterized by X-ray diffraction.
      The solid state metrical parameters, in combination with infrared and Mossbauer
      spectroscopic data, establish ferrous compounds with doubly reduced chelates.
      Each new bis(imino)pyridine iron dinitrogen compound was screened for the
      catalytic hydrogenation of ethyl-3-methylbut-2-enoate, and the compound bearing
      the smallest aryl substituent, [((Me)PDI)Fe(N(2))](2)(mu(2)-N(2)), offers
      significant improvement over the original ((iPr)PDI)Fe(N(2))(2) pre-catalyst and
      is one of the most active iron pre-catalysts known.

PMID- 20143848
TI  - Spectroscopic and structural studies of difluorophosphoryl azide F2P(O)N3,
      difluorophosphoryl isocyanate F2P(O)NCO, and difluorophosphoric acid anhydride,
      F2(O)POP(O)F2.
AB  - Difluorophosphoryl azide, F(2)P(O)N(3), was fully characterized by (19)F, (31)P,
      (14)N, and (15)N NMR, as well as by IR (gas, Ar-matrix), and Raman (liquid,
      solid) spectroscopy. For comparison the vibrational spectra of the isoelectronic
      difluorophosphoryl isocyanate, F(2)P(O)NCO was also studied. Both molecules were
      found to exist as single rotamers in the gas, liquid, and solid states. Their
      solid-state structures were determined by X-ray crystallography as the rotamers
      with the P=O bond being cis to the pseudohalide groups (with respect to the P-N
      bond). The F(2)P(O)N(3) molecule exhibits approximate C(s) symmetry (phi(O1P1
      N1N2) = -0.7(3) degrees), while F(2)P(O)NCO is significantly distorted from C(s)
      symmetry (phi(O1P1-N1C1) = -18.9(5) degrees) because of intermolecular C...O
      contacts. The crystal structure of difluorophosphoric acid anhydride,
      F(2)(O)POP(O)F(2), was also determined, possessing crystallographic C(2) symmetry
      with the two F(2)PO groups slightly staggered by 10.66(7) degrees along the P...P
      vector, and a P-O-P angle of 140.89(10) degrees for the bridging oxygen atom. The
      experimental results are supported by quantum chemical calculations, and the
      conformational properties of F(2)P(O)N(3) and F(2)P(O)NCO are discussed.

PMID- 20143849
TI  - Proton affinity of the oxyanion hole in the active site of ketosteroid isomerase.
AB  - The absorption spectra of a series of inhibitors bound at the active site of
      Delta(5)-3-ketosteroid isomerase from Pseudomonas putida were found to exhibit
      substantial variations in the contributions of the protonated and deprotonated
      forms. Systematic variation of the inhibitor solution pK(a) combined with a
      method of quantifying the contributions of each protonation state showed the
      oxyanion hole in the active site of wild-type Delta(5)-3-ketosteroid isomerase to
      have a proton affinity equal to a solution pK(a) of 10.05 +/- 0.03, which is
      similar to the measured pK(a) (10.0) of the reaction intermediate. This
      observation supports the prediction of Cleland, Kreevoy, Frey, Gassman, and Gerlt
      that an enzyme utilizing a strong hydrogen bond for catalysis matches the proton
      affinity of the protein to the intermediate [Cleland, W. W., and Kreevoy, M. M.
      (1994) Science 264, 1887-1890; Frey, P. A., Whitt, S., and Tobin, J. (1994)
      Science 264, 1927-1930; Gerlt, J. A., and Gassman, P. G. (1993) Biochemistry 32,
      11934-11952]. As the difference in proton affinity decreases, the strength of the
      hydrogen bond increases, and the closely matched proton affinity between the
      active site and the reaction intermediate supports the possibility that a short,
      strong hydrogen bond is catalytically relevant in Delta(5)-3-ketosteroid
      isomerase.

PMID- 20143850
TI  - Recognition of achiral and chiral ammonium salts by neutral ditopic receptors
      based on chiral salen-UO2 macrocycles.
AB  - A mononuclear (M20) and a dinuclear (M40) uranyl chiral macrocyclic complex,
      incorporating both a salen unit containing two phenyl rings linked to a chiral
      diimine bridge and the (R)-BINOL unit, behaves as an efficient ditopic receptor
      for achiral and chiral quaternary ammonium salts. Binding affinities in
      chloroform solution have been measured for 1:1 complexes of many quaternary salts
      encompassing tetramethylammonium (TMA), tetraethylammonium (TEA),
      tetrabutylammonium (TBA), and acetylcholine (ACh), as well as trimethylanilinium
      (TriMAn), benzyltrimethylammonium (BnTriMA), (alpha
      methylbenzyl)trimethylammonium and pyrrolidinium cations. The anion of the salt
      is bound by the hard Lewis acidic uranyl site, with an increasing binding
      efficiency on increasing the anion hardness (I(-) < Br(-) < Cl(-)), whereas CH-pi
      or pi-pi attractions by binapthyl moiety, or the salicylaldehyde unit, or the
      phenyl rings of diimine bridge ensure the recognition of the cation partner.
      Optimized structures of receptor-anion-cation ternary complexes obtained by MM
      calculations are supported by 2D-ROESY NMR measurements.

PMID- 20143851
TI  - Diffusiophoresis of a charge-regulated spherical particle normal to two parallel
      disks.
AB  - The diffusiophoresis of a charge-regulated spherical particle normal to two
      parallel disks as a response to an applied uniform electrolyte concentration
      gradient is modeled theoretically. The fixed charge on the particle surface comes
      from the dissociation/association reactions of the functional groups, yielding a
      charge-regulated surface, which simulates biological cells. Numerical simulations
      are conducted to examine the behavior of a particle under various conditions: the
      parameters considered in the simulation include the thickness of the double
      layer, the charged conditions on the particle surface, the relative size of the
      particle, and the particle-disk distance. Because the diffusiophoretic mobility
      of a particle can be dominated by chemiphoresis, electrophoresis, or osmotic
      flow, the diffusiophoretic behavior of the particle is complicated. For instance,
      the diffusiophoretic mobility may have two local maximums and a local minimum as
      the thickness of the double layer varies. This behavior is of practical
      significance if diffusiophoresis is adopted as a separation operation or as a
      tool to characterize the surface properties of a particle.

PMID- 20143852
TI  - Effect of dissolved organic matters on napropamide availability and ecotoxicity
      in rapeseed ( Brassica napus ).
AB  - Napropamide is a herbicide widely used for controlling annual weeds. Substantial
      use of napropamide in recent years has led to its bioaccumulation in ecosystems
      and thus contamination to crops. Meanwhile, application of dissolved organic
      matters (DOMs) to soils in the form of compost, sludge, or plant residues has
      become a popular practice in agriculture management owning to its low cost and
      recycling of nutrients. However, whether DOMs affect environmental behaviors of
      herbicides in soil-plant systems is poorly understood. This study investigated
      napropamide accumulation and biological responses as affected by DOMs in Brassica
      napus . Plants exposed to 0-16 mg/kg napropamide show inhibited growth and
      oxidative damage. Treatment with 50 mg of DOC/kg DOMs derived from either sludge
      or straw improved plant growth and reduced napropamide accumulation in plants.
      Both DOMs reduced the production of reactive oxygen species (ROS) and the
      activities of antioxidative enzymes in napropamide-exposed plants. Analysis of FT
      IR spectra confirmed the difference between structures of the two DOMs.
      Additional evidence was provided by three-dimensional excitation-emission matrix
      (EEM) fluorescence spectra to demonstrate the DOM-napropamide complex formed
      during the process of the interaction.

PMID- 20143853
TI  - Effects of fusarium infection on the phenolics in emmer and naked barley.
AB  - Inoculated or non-inoculated naked barley and emmer cultivars were investigated
      with regard to their influence on phenolic acid profiles and their arabinoxylan
      content. Two groups of phenolic compounds were differentiated-methanol-soluble
      and hydrolyzable covalent-bound phenolic compounds. Chromatographic methods were
      applied for their analysis. The results showed ferulic acid as the predominant
      phenol in both total and covalent-bound fractions. The inoculation significantly
      reduced the ferulic acid content within a range of 5.6-6.6% in the two cereals
      and all their cultivars. Naked barley cultivars additionally contained the
      flavonoid catechin in the soluble fraction. The innoculation led here to a
      significant increase in the catechin content of about 4.5%. These results
      document an induction of the synthesis of catechin in naked barley after
      artificial Fusarium infection, whereas the ferulic acid content declined.

PMID- 20143854
TI  - Comparison of five endogenous reference genes for specific PCR detection and
      quantification of Brassica napus.
AB  - Five previously reported Brassica napus endogenous reference genes, including
      acetyl-CoA carboxylase gene (BnACCg8), phosphoenolpyruvate carboxylase (PEP),
      oleoyl hydrolase gene (FatA), high-mobility-group protein I/Y gene (HMG-I/Y) and
      cruciferin A gene (CruA), were analyzed for their PCR specificity between B.
      napus and other species and the quantification stability among different B. napus
      cultivars. PCR and sequencing results indicated that none of these systems was
      species-specific as required by the genetically modified organism labeling
      policy. When these genes were employed in real-time PCR, BnACCg8 and HMG-I/Y
      systems showed relatively greater heterogeneity among 10 different cultivars. The
      sequencing results showed that the single nucleotide polymorphism in the primer
      binding sites was the potential source of the instability in the HMG-I/Y system.
      The bias of BnACCg8 was thought to be associated with the inconsistent copy
      number of this gene.

PMID- 20143855
TI  - Microbioreactors for Raman microscopy of stromal cell differentiation.
AB  - We present the development of microbioreactors with a sensitive and accurate
      optical coupling to a confocal Raman microspectrometer. We show that such devices
      enable in situ and in vitro investigation of cell cultures for tissue engineering
      by chemically sensitive Raman spectroscopic imaging techniques. The optical
      resolution of the Raman microspectrometer allows recognition and chemical
      analysis of subcellular features. Human bone marrow stromal cells (hBMSCs) have
      been followed after seeding through a phase of early proliferation until
      typically 21 days later, well after the cells have differentiated to osteoblasts.
      Long-term perfusion of cells in the dynamic culture conditions was shown to be
      compatible with experimental optical demands and off-line optical analysis. We
      show that Raman optical analysis of cells and cellular differentiation in
      microbioreactors is feasible down to the level of subcellular organelles during
      development. We conclude that microbioreactors combined with Raman
      microspectroscopy are a valuable tool to study hBMSC proliferation,
      differentiation, and development into tissues under in situ and in vitro
      conditions.

PMID- 20143856
TI  - Diphosphine-catalyzed mixed double-Michael reaction: a unified synthesis of
      indolines, dihydropyrrolopyridines, benzimidazolines, tetrahydroquinolines,
      tetrahydroisoquinolines, dihydrobenzo-1,4-oxazines, and dihydrobenzo-3,1
      oxazines.
AB  - Seven different types of benzannulated N-heterocycles-indolines,
      dihydropyrrolopyridines, benzimidazolines, dihydrobenzo-3,1-oxazines,
      benzomorpholines, tetrahydroquinolines, and tetrahydroisoquinolines-can be
      obtained from simple dinucleophiles and electron-deficient acetylenes in one
      synthetic step. This powerful methodology was made possible through the use of
      diphenylphosphinopropane (DPPP) as the catalyst, with acetic acid and sodium
      acetate used as additives in some cases. The benzannulated N-heterocycles were
      isolated in excellent yields under mild metal-free conditions; they were purified
      without the need for aqueous workups.

PMID- 20143857
TI  - Diastereo- and enantioselective synthesis of alpha,gamma-diaminobutyric acid
      derivatives via Cu-catalyzed asymmetric Michael reaction.
AB  - The first highly diastereo- and enantioselective catalytic asymmetric Michael
      addition of glycine derivatives to nitroalkenes have been developed. The
      enantioselectivity of ortho-substituted products can be significantly improved by
      using a new 1,2-P,N-ferrocene ligand L5. The alpha,gamma-diaminoacid derivative
      was obtained without the loss of optical activity from the adduct.

PMID- 20143858
TI  - Natural biopolymers: novel templates for the synthesis of nanostructures.
AB  - Biological systems such as proteins, viruses, and DNA have been most often
      reported to be used as templates for the synthesis of functional nanomaterials,
      but the properties of widely available biopolymers, such as cellulose, have been
      much less exploited for this purpose. Here, we report for the first time that
      cellulose nanocrystals (CNC) have the capacity to assist in the synthesis of
      metallic nanoparticle chains. A cationic surfactant, cetyltrimethylammonium
      bromide (CTAB), was critical to nanoparticle stabilization and CNC surface
      modification. Silver, gold, copper, and platinum nanoparticles were synthesized
      on CNCs, and the nanoparticle density and particle size were controlled by
      varying the concentration of CTAB, the pH of the salt solution, and the reduction
      time.

PMID- 20143859
TI  - Tip geometry controls adhesive states of superhydrophobic surfaces.
AB  - Inspired by biological attachment systems, aligned polystyrene (PS) nanopillars
      terminating in flat, concave tips and nanotubes were fabricated by a simple and
      reproducible method. All the obtained surfaces show both the contact angles
      larger than 150 degrees (superhydrophobicity) and high adhesion of water to it.
      The tip geometry plays an important role in determining the adhesive property.
      Surface with the concave tips has the highest adhesion, and then the surface with
      flat tips, whereas aligned nanotube surface has a relatively lower adhesion.
      Besides different van der Waals forces between the PS surfaces and water, another
      important factor, i.e., different negative pressures produced by the different
      volumes of sealed air, may be the crucial factor for their different adhesions.
      These findings provide the experimental evidence of the influence of the tip
      geometry on the adhesion of structured superhydrophobic surfaces, which is
      helpful for us to further understand the biological attachment systems and to
      optimum design of artificial analogues.

PMID- 20143861
TI  - Highly efficient methyl ketone synthesis with photoactivated acetone and olefins
      assisted by Mg(II)-exchanged zeolite Y.
AB  - We previously found that photoirradiation of an acetone/water mixture containing
      olefins affords the corresponding methyl ketones highly efficiently and
      selectively via a water-assisted C-C coupling between the acetonyl radical and
      olefins (Org. Lett. 2008, 10, 3117-3120). The reaction proceeds at room
      temperature without any additives and has a potential to be a powerful method for
      methyl ketone synthesis. Here we report that an addition of Mg(2+)-exchanged
      zeolite Y (MgY) to the above photoreaction system accelerates the methyl ketone
      formation, while maintaining high selectivity. Ab initio molecular orbital
      calculation reveals that the accelerated methyl ketone formation is due to the
      electrostatic interaction between Mg(2+) and excited-state acetone. This leads to
      a charge polarization of the carbonyl moiety of excited-state acetone and
      accelerates the hydrogen abstraction from ground-state acetone (acetonyl radical
      formation). This promotes efficient addition of the acetonyl radical to olefins,
      resulting in methyl ketone formation enhancement. Adsorption experiments reveal
      that accumulation of olefins inside the zeolite pore also affects efficient
      radical addition to olefins. The present process successfully produces various
      methyl ketones with very high yield, and the MgY recovered can be reused for
      further reaction without loss of activity.

PMID- 20143862
TI  - Imidazolium bromide-based ionic liquid assisted improved activity of trypsin in
      cationic reverse micelles.
AB  - The present work reports the imidazolium-based ionic liquids (ILs) assisted
      enhancement in activity of water-pool solubilized enzyme trypsin in cationic
      reverse micelles of CTAB. A set of imidazolium ILs (1-alkyl-3-methyl imidazolium
      bromides) were prepared with varying lengths of their side arm which results in
      the differential location of these organic salts in the reverse micelles. The
      different ILs offered varied activating effects on the biocatalyst. The activity
      of trypsin improved approximately 30-300% in the presence of 0.1-10 mM of
      different ILs in reverse micelles of CTAB. Trypsin showed approximately 300% (4
      fold) increment in its activity in the presence of IL 2 (1-ethyl-3-methyl
      imidazolium bromide, EMIMBr) compared to that observed in the absence of IL in
      CTAB reverse micelles. The imidazolium moiety of the IL, resembling the histidine
      amino acid component of the catalytic triad of hydrolases and its Br(-)
      counterion, presumably increases the nucleophilicity of water in the vicinity of
      the enzyme by forming a hydrogen bond that facilitates the enzyme-catalyzed
      hydrolysis of the ester. However, the ILs with increasing amphiphilic character
      had little to no effect on the activity of trypsin due to their increased
      distance from the biocatalyst, as they tend to get localized toward the
      interfacial region of the aggregates. Dynamic light scattering experimentation
      was carried out in the presence of ILs to find a possible correlation between the
      trypsin activity and the size of the aggregates. In concurrence with the observed
      highest activity in the presence of IL 2, the circular dichroism (CD) spectrum of
      trypsin in CTAB reverse micelles doped with IL 2 exhibited the lowest mean
      residue ellipticity (MRE), which is closest to that of the native protein in
      aqueous buffer.

PMID- 20143863
TI  - Stereoselective synthesis of cis- and trans-2,3-disubstituted tetrahydrofurans
      via oxonium-prins cyclization: access to the cordigol ring system.
AB  - SnBr(4)-promoted oxonium-Prins cyclizations to form 2,3-disubstituted
      tetrahydrofurans (THFs) are reported. In the absence of an internal nucleophile,
      the carbocation intermediates are trapped by bromide to give 2,3-cis- and 2,3
      trans-configured products; two variations with intramolecular trapping are also
      reported. One of these allows a single-step stereocontrolled synthesis of the
      core 2,3-cis-THF ring system of cordigol, a fungicidal polyphenol from the stem
      bark of Cordia goetzei. For this latter transformation, a stepwise oxonium
      Prins/cation trapping pathway rather than orthoquinonemethide formation/hetero
      Diels-Alder cycloaddition is supported computationally.

PMID- 20143864
TI  - Investigation of the relationship between hydrogen bonds and macroscopic
      properties in hybrid core-shell gamma-Fe2O3-P(NIPAM-AAS) microgels.
AB  - We investigate in a hybrid material the interactions existing between magnetic
      nanoparticles of gamma-Fe(2)O(3) and the polymer matrix constituted by core-shell
      poly(N-isopropylacrylamide-sodium acrylate) microgels. These interactions provoke
      the shifting of the microgel volume phase transition to higher temperatures when
      the amount of gamma-Fe(2)O(3) increases. The study was performed using different
      techniques such as incoherent quasi-elastic neutron scattering (IQNS), infrared
      spectroscopy (FTIR-ATR), and dynamic light scattering (DLS). Below the low
      critical solution temperature (LCST) of the polymer, the IQNS data confirm that
      the presence of inorganic nanoparticles affects the PNIPAM chain motions. Thus,
      in the swollen state both the mean-square displacement of the polymer segments
      and the diffusive motion of the polymer chains decrease as the iron oxide content
      increases. The FTIR-ATR study indicates that the reduction of vibrational and
      diffusional motions of the polymer chains is due to the formation of hydrogen
      bonds between the amide groups of the polymer matrix and the OH groups of the
      magnetic nanoparticles. The creation of this hybrid complex would explain the
      reduction of the swelling capacity with increasing the iron content in the
      microgels. Furthermore, this interaction could also explain the shift of the
      polymer LCST to higher temperatures as due to the extra energy required by the
      system to break the hydrogen bonds prior to the PNIPAM collapse.

PMID- 20143865
TI  - Composite au nanostructures for fluorescence studies in visible light.
AB  - We present results from composite plasmonic nanostructures designed to achieve
      the cascaded enhancement of electromagnetic fields at optical frequencies. Our
      structures comprise a small metallic nanodisc suspended above a larger disk. We
      probe the optical properties of these structures by coating them with a layer of
      a visible-light fluorophore and observing fluorescence signals with the help of
      scanning confocal microscopy. A 43 +/- 5-fold increase in the far-field
      fluorescence signal has been observed for two-tier composite nanostructures, when
      compared to the signal obtained from individual nanodiscs. Our results offer the
      prospect of using such nanostructures for field concentration, optical
      manipulation of nanoobjects, chemical and biological sensing.

PMID- 20143866
TI  - Effect of charge trapping on geminate recombination and polymer solar cell
      performance.
AB  - In this letter, we examine the effect of charge trapping on geminate
      recombination and organic photovoltaic performance using a Monte Carlo model. We
      alter the degree of charge trapping by considering energetic disorder to be
      spatially uncorrelated or correlated. On correlating energetic disorder, and so
      reducing the degree of trapping, it is found that power conversion efficiency of
      blend and bilayer devices improves by factors of 3.1 and 2.6, respectively. These
      results are related to the experimental data and quantum chemical calculations
      for poly[9,9-dioctylfluorene-co-bis-N,N'-(4-butylphenyl)-bis-N,N'-phenyl-1,4
      phenylenediamine] (PFB)/poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8BT) as
      well as poly(3-hexylthiophene) (P3HT)/(6,6)-phenyl-C(61)-butyric acid methyl
      ester (PCBM) solar cell systems. The minimization of traps at the heterojunction
      between electron- and hole-accepting materials, perhaps by molecular design,
      appears to be a promising strategy to achieve large gains in PV performance. It
      is also shown that macroscopically measurable quantities such as mobility and
      energetic disorder are not necessarily good predictors of nanoscale geminate
      recombination process.

PMID- 20143867
TI  - The visualized polarity-sensitive magnetic nanoparticles.
AB  - Three polarity-sensitive organic molecules (DIAA, DIUA, and DISA) were designed
      and synthesized for functionalizing high-quality superparamagnetic Fe(3)O(4)
      nanoparticles (NPs) via the ligand exchange strategy to prepare polarity
      sensitive Fe(3)O(4) NPs. The functional group is chosen to be the carboxyl group
      (one for DIAA and DIUA, two for DISA) that is a universal coordinating site for
      iron oxide NPs. The method for binding these functional molecules onto the
      surface of the NPs is simple and straightforward. Among the three molecules, the
      DISA molecules passivate the NPs' surface most efficiently owing to their
      particular structure with two carboxyl groups and a general good solubility. The
      DISA-functionalized Fe(3)O(4) NPs (DISA-Fe(3)O(4) NPs) display distinctly
      different fluorescence emissions in various solvents of different polarities with
      the magnetism well preserving. The prepared polarity-sensitive Fe(3)O(4) NPs that
      are dual functional can be used as a visualized polarity sensor and perform NPs'
      superparamagnetic properties simultaneously. It also provides a conceptual design
      for preparing the polarity-sensitive nanomaterials with multifunction.

PMID- 20143868
TI  - Ternary lipid bilayers containing cholesterol in a high curvature silica xerogel
      environment.
AB  - The phase behavior of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2
      distearoyl-sn-glycero-3-phosphocholine (DSPC) (1/1 mol ratio)/cholesterol (0-60
      mol %) supported lipid bilayers agreed with a DOPC/DSPC/cholesterol ternary phase
      diagram by Zhao et al. when a mica support was used (Zhao, J.; Wu, J.; Heberle,
      F. A.; Mills, T. T.; Klawitter, P.; Huang, G.; Costanza, G.; Feigenson, G. W.
      Biochim. Biophys. Acta, Biomembr. 2007, 1768, 2764-2776). However, when a silica
      xerogel support was used, the phase behavior deviated from the phase diagram.
      Specifically, miscibility and trend lines of DSPC-rich domain area fraction,
      domain shape, and domain size versus cholesterol, obtained by analysis of
      fluorescence and atomic force microscopy (AFM) images, were as expected for mica
      supported lipid bilayers, but were substantially stretched to higher cholesterol
      concentrations for silica xerogel-supported lipid bilayers. In addition, this
      behavior was found in three other ternary lipid compositions substituting
      slightly shorter acyl chain lengths in comparison to DSPC or a saturated lipid
      versus unsaturated DOPC. Qualitative comparison of domain characteristics of
      DOPC/DSPC/cholesterol (0 and 15 mol %) bilayers supported by silica xerogel,
      mica, borosilicate glass, and quartz showed that the networked surface layer of
      high curvature (0.04 nm(-1)) silica beads was the dominant influence as opposed
      to the surface chemistry. Based upon the literature, we postulate two curvature
      based mechanisms that explain our results. In the first mechanism, cholesterol
      was transferred from the higher curvature supported lipid bilayer to the lower
      curvature vesicles in the medium during the vesicle fusion and thermal cooling
      step, resulting in a lowered cholesterol concentration of the supported lipid
      bilayer. In the second mechanism, high curvature promoted sustained lipid
      demixing as the cholesterol concentration was increased, thus creating a new
      phase diagram in which coexisting phases persist to a higher cholesterol
      concentration. These results suggest that a surface layer of high curvature
      features can be used to observe and study curvature-induced intrabilayer
      transport or demixing over large areas and that curvature can play an important
      role in sorting and localization of biomembrane components.

PMID- 20143869
TI  - GlycoExtractor: a web-based interface for high throughput processing of HPLC
      glycan data.
AB  - Recently, an automated high-throughput HPLC platform has been developed that can
      be used to fully sequence and quantify low concentrations of N-linked sugars
      released from glycoproteins, supported by an experimental database (GlycoBase)
      and analytical tools (autoGU). However, commercial packages that support the
      operation of HPLC instruments and data storage lack platforms for the extraction
      of large volumes of data. The lack of resources and agreed formats in glycomics
      is now a major limiting factor that restricts the development of bioinformatic
      tools and automated workflows for high-throughput HPLC data analysis.
      GlycoExtractor is a web-based tool that interfaces with a commercial HPLC
      database/software solution to facilitate the extraction of large volumes of
      processed glycan profile data (peak number, peak areas, and glucose unit values).
      The tool allows the user to export a series of sample sets to a set of file
      formats (XML, JSON, and CSV) rather than a collection of disconnected files. This
      approach not only reduces the amount of manual refinement required to export data
      into a suitable format for data analysis but also opens the field to new
      approaches for high-throughput data interpretation and storage, including
      biomarker discovery and validation and monitoring of online bioprocessing
      conditions for next generation biotherapeutics.

PMID- 20143870
TI  - Site-specific IGFBP-1 hyper-phosphorylation in fetal growth restriction: clinical
      and functional relevance.
AB  - Phosphorylation enhances IGFBP-1 binding to IGF-I, thereby limiting the
      bioavailability of IGF-I that may be important in fetal growth. Our goal in this
      study was to determine whether changes in site-specific IGFBP-1 phosphorylation
      were unique to fetal growth restriction. To establish a link, we compared IGFBP-1
      phosphorylation (sites and degree) in amniotic fluid from FGR (N = 10) and
      controls (N = 12). The concentration of serine phosphorylated IGFBP-1 showed a
      negative correlation with birth weight in FGR (P = 0.049). LC-MS/MS analysis
      revealed all four previously identified phosphorylation sites (Ser98, Ser101,
      Ser119, and Ser169) to be common to FGR and control groups. Relative
      phosphopeptide intensities (LC-MS) between FGR and controls demonstrated 4-fold
      higher intensity for Ser101 (P = 0.026), 7-fold for Ser98/Ser101 (P = 0.02), and
      23-fold for Ser169 (P = 0.002) in the FGR group. Preliminary BIAcore data
      revealed 4-fold higher association and 1.7-fold lower dissociation constants for
      IGFBP-1/IGF-I in FGR. A structural model of IGFBP-1 bound to IGF-I indicates that
      all the phosphorylation sites are on relatively mobile regions of the IGFBP-1
      sequence. Residues Ser98, Ser101, and Ser169 are close to structured regions that
      are involved in IGF-I binding and, therefore, could potentially make direct
      contact with IGF-I. On the other hand, residue Ser119 is in the middle of the
      unstructured linker that connects the N- and C-terminal domains of IGFBP-1. The
      model is consistent with the assumption that residues Ser98, Ser101, and Ser169
      could directly interact with IGF-I, and therefore phosphorylation at these sites
      could change IGF-I interactions. We suggest that site-specific increase in IGFBP
      1 phosphorylation limits IGF-I bioavailability, which directly contributes to the
      development of FGR. This study delineates the potential role of higher
      phosphorylation of IGFBP-1 in FGR and provides the basis to substantiate these
      findings with larger sample size.

PMID- 20143871
TI  - A conserved mode of protein recognition and binding in a ParD-ParE toxin
      antitoxin complex.
AB  - Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with
      functional roles in plasmid inheritance, environmental stress response, and cell
      development. ParDE family TA systems are broadly conserved on plasmids and
      bacterial chromosomes and have been well characterized as genetic elements that
      promote stable plasmid inheritance. We present a crystal structure of a
      chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.6 A
      resolution. This TA system forms an alpha(2)beta(2) heterotetramer in the crystal
      and in solution. The toxin-antitoxin binding interface reveals extensive polar
      and hydrophobic contacts of ParD antitoxin helices with a conserved recognition
      and binding groove on the ParE toxin. A cross-species comparison of this complex
      structure with related toxin structures identified an antitoxin recognition and
      binding subdomain that is conserved between distantly related members of the
      RelE/ParE toxin superfamily despite a low level of overall primary sequence
      identity. We further demonstrate that ParD antitoxin is dimeric, stably folded,
      and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in
      which antitoxin undergoes a disorder-to-order transition upon toxin binding does
      not apply to this chromosomal ParD-ParE TA system.

PMID- 20143872
TI  - Blood folate status and expression of proteins involved in immune function,
      inflammation, and coagulation: biochemical and proteomic changes in the plasma of
      humans in response to long-term synthetic folic acid supplementation.
AB  - We used plasma proteomics to identify human proteins responsive to folate status.
      Plasma was collected from subjects treated with placebo or 1.2 mg of folic acid
      daily for 12 weeks in a randomized controlled trial. Homocysteine and folate were
      measured by immunoassay and uracil misincorporation by electrophoresis. The
      plasma proteome was assessed by 2-D gel electrophoresis, and proteins were
      identified by LC MS/MS. 5-methylTHF increased 5-fold (P = 0.000003) in response
      to intervention. Red cell folate doubled (P = 0.013), and lymphocyte folate
      increased 44% (P = 0.0001). Hcy and uracil dropped 22% (P = 0.0005) and 25% (P =
      0.05), respectively. ApoE A-1, alpha-1-antichymotrypsin, antithrombin, and serum
      amyloid P were downregulated, while albumin, IgM C, and complement C3 were
      upregulated (P < 0.05). More than 60 proteins were significantly associated with
      folate pre- and postintervention (P < 0.01). These were categorized into
      metabolic pathways related to complement fixation (e.g., C1, C3, C4, Factor H,
      Factor 1, Factor B, clusterin), coagulation (e.g., antithrombin, alpha-1
      antitrypsin, kininogen) and mineral transport (e.g., transthyretin, haptoglobin,
      ceruloplasmin). Low folate status pre- and post-treatment were associated with
      lower levels of proteins involved in activation and regulation of immune function
      and coagulation. Supplementation with synthetic folic acid increased expression
      of these proteins but did not substantially disrupt the balance of these
      pathways.

PMID- 20143874
TI  - Superglide at an internal incommensurate boundary.
AB  - The intriguing possibility of frictionless gliding of one solid surface on
      another has been predicted for certain incommensurate interfaces in crystals,
      based on Aubry's solution to the Frenkel-Kontorova model of a harmonic chain in a
      periodic potential field. Here we test this prediction for grain boundaries by
      comparing atomistic simulations with direct experimental observations on the
      structure and load-deformation behavior of gold nanopillars containing a root-two
      incommensurate grain boundary. The simulations show supergliding at this boundary
      limited by finite-size effects which cause edges to act as defects of the
      incommensurate structure. Structural relaxation at the edges generates stacking
      faults, dislocations, and asymmetric surface steps. These features as well as the
      related load-displacement behavior are replicated by experimental observations on
      the compression of nanopillars using a quantitative nanoindentation device inside
      a transmission electron microscope. The good agreement between the observed and
      predicted behavior suggests that incommensurate interfaces could play an
      important role in the deformation of polycrystalline materials.

PMID- 20143875
TI  - Introduction to selective functionalization of C-H bonds.

PMID- 20143876
TI  - Emergence of palladium(IV) chemistry in synthesis and catalysis.

PMID- 20143877
TI  - C-H bond activations by metal oxo compounds.

PMID- 20143878
TI  - Structural features of intra- and intermolecular G-quadruplexes derived from
      telomeric repeats.
AB  - The 3' strand of telomeres is composed of tandem repeats of short G-rich
      sequences which protrude as single-stranded DNA overhangs. These repeats are
      G(3)T(2)A in humans and G(4)T(2) and G(4)T(4) in the ciliates Tetrahymena and
      Oxytricha, respectively. We analyzed different quadruplex-forming sequences
      derived from telomeric sequences, G(3+k)(T(n+k)G(3+k))(3) and
      G(3+k)(T(2)AG(3+k))(3), in the presence of Li(+), Na(+), and K(+) through the use
      of circular dichroism, UV spectroscopy, and electrophoresis, where k = 0 or 1 and
      n = 1-3. Results obtained under the given conditions can provide more detailed
      information about the quadruplex structure. The major findings are as follows.
      (i) G-Repeats in solution form a mix of topologically different structures; only
      G(3)(T(2)G(3))(3) and G(3)(TG(3))(3) repeats preferentially form the parallel
      interstrand structure. (ii) The Tetrahymena repeat can form at least two
      intramolecular conformers with different strand orientations and levels of
      stability. (iii) G-Quadruplex conformation and molecularity strongly depend on
      the type and concentration of ions used in the solution. The formation of
      intramolecular quadruplexes is governed by the length of the loops connecting G
      runs. Intermolecular G-quadruplex forms are more likely to form in a higher
      concentration of ions for sequences where G-runs are separated by only one or two
      nucleotides.

PMID- 20143879
TI  - Mutagenic potential of DNA glycation: miscoding by (R)- and (S)-N2-(1
      carboxyethyl)-2'-deoxyguanosine.
AB  - Elevated circulating glucose resulting from complications of obesity and
      metabolic disease can result in the accumulation of advanced glycation end
      products (AGEs) of proteins, lipids, and DNA. The formation of DNA-AGEs assumes
      particular importance as these adducts may contribute to genetic instability and
      elevated cancer risk associated with metabolic disease. The principal DNA-AGE,
      N(2)-(1-carboxyethyl)-2'-deoxyguanosine (CEdG), is formed as a mixture of R and S
      isomers at both the polymer and monomer levels. In order to examine the miscoding
      potential of this adduct, oligonucleotides substituted with (R)- and (S)-CEdG and
      the corresponding triphosphates (R)- and (S)-CEdGTP were synthesized, and base
      pairing preferences for each stereoisomer were examined using steady-state
      kinetic approaches. Purine dNTPs were preferentially incorporated opposite
      template CEdG when either the Klenow (Kf(-)) or Thermus aquaticus (Taq)
      polymerases were used. The Kf(-) polymerase preferentially incorporated dGTP,
      whereas Taq demonstrated a bias for dATP. Kf(-) incorporated purines opposite the
      R isomer with greater efficiency, but Taq favored the S isomer. Incorporation of
      (R)- and (S)-CEdGTP only occurred opposite dC and was catalyzed by Kf(-) with
      equal efficiencies. Primer extension from a 3'-terminal CEdG was observed only
      for the R isomer. These data suggest CEdG is the likely adduct responsible for
      the observed pattern of G transversions induced by exposure to elevated glucose
      or its alpha-oxoaldehyde decomposition product methylglyoxal. The results imply
      that CEdG within template DNA and the corresponding triphosphate possess
      different syn/anti conformations during replication which influence base-pairing
      preferences. The implications for CEdG-induced mutagenesis in vivo are discussed.

PMID- 20143880
TI  - Vimentin is a functional partner of hormone sensitive lipase and facilitates
      lipolysis.
AB  - Lipolysis involves a number of components including signaling pathways, droplet
      associated proteins, and lipases such as hormone-sensitive lipase (HSL). We used
      surface enhanced laser desorption/ionization time-of-flight mass spectroscopy to
      identify cellular proteins that might interact with HSL and potentially influence
      lipolysis. Using recombinant HSL as bait on protein chips, clusters of proteins
      of 14.7-18.9, 25.8-26.8, 36.1, 44.3-49.1, and 53.7 kDa were identified that
      interact with HSL, particularly when lysates were examined from beta-agonist
      treated mouse adipocytes. The ability to detect these interacting proteins was
      markedly diminished when the adipocytes were treated with insulin. A very similar
      pattern of proteins was identified when anti-HSL IgG was used as the bait.
      Following immunocapture, the identification of the prominent 53.7 kDa protein was
      carried out by tryptic digestion and MS analysis and determined to be vimentin.
      The interaction of HSL with vimentin, and its hormonal dependence, was confirmed
      by coimmunoprecipitation. beta-Agonist stimulated lipolysis and the rate of HSL
      translocation were impaired in vimentin null adipocytes, even though normal
      amounts of lipases and droplet-associated proteins are expressed. The current
      studies provide evidence that vimentin participates in lipolysis through direct,
      hormonally regulated interactions with HSL.

PMID- 20143881
TI  - Impact of environmental chemicals on key transcription regulators and correlation
      to toxicity end points within EPA's ToxCast program.
AB  - Exposure to environmental chemicals adds to the burden of disease in humans and
      wildlife to a degree that is difficult to estimate and, thus, mitigate. The
      ability to assess the impact of existing chemicals for which little to no
      toxicity data are available or to foresee such effects during early stages of
      chemical development and use, and before potential exposure occurs, is a pressing
      need. However, the capacity of the current toxicity evaluation approaches to meet
      this demand is limited by low throughput and high costs. In the context of EPA's
      ToxCast project, we have evaluated a novel cellular biosensor system (Factorial
      (1) ) that enables rapid, high-content assessment of a compound's impact on gene
      regulatory networks. The Factorial biosensors combined libraries of cis- and
      trans-regulated transcription factor reporter constructs with a highly
      homogeneous method of detection enabling simultaneous evaluation of multiplexed
      transcription factor activities. Here, we demonstrate the application of the
      technology toward determining bioactivity profiles by quantitatively evaluating
      the effects of 309 environmental chemicals on 25 nuclear receptors and 48
      transcription factor response elements. We demonstrate coherent transcription
      factor activity across nuclear receptors and their response elements and that
      Nrf2 activity, a marker of oxidative stress, is highly correlated to the overall
      promiscuity of a chemical. Additionally, as part of the ToxCast program, we
      identify molecular targets that associate with in vivo end points and represent
      modes of action that can serve as potential toxicity pathway biomarkers and
      inputs for predictive modeling of in vivo toxicity.

PMID- 20143882
TI  - Linker formation in an overcharged complex of two dendrimers and linear
      polyelectrolyte.
AB  - The complexes formed by two dendrimers with charged terminal groups and
      oppositely charged long linear polyelectrolyte (LPE) have been studied using
      Brownian dynamics simulations. The structural properties of the complexes and
      their dependence on the LPE chain length were investigated. It was observed that
      dendrimers in the considered complexes are sufficiently overcharged; i.e., the
      number of adsorbed LPE monomers is larger than required for the neutralization.
      The degree of overcharging increases with the increase of the LPE length and is
      accompanied by the linker appearance until saturation in overcharging is reached.
      Nonmonotonic dependence of the linker size on the LPE length was observed. To
      describe the structural properties of the complexes formed by two macroions and a
      polyelectrolyte chain, the correlation theory has been developed.

PMID- 20143883
TI  - On the antibacterial action of cyclic peptides: insights from coarse-grained MD
      simulations.
AB  - [RRKWLWLW] cyclic peptides have been shown to exhibit remarkable in vitro and in
      vivo antibacterial activity. Peptides alike seem to be promising for the
      development of new compounds to combat microbial pathogens, yet the molecular
      level understanding of their mechanism of action remains unclear. Here, we use
      coarse-grained (CG) molecular dynamics (MD) simulations of these cyclic peptides
      interacting with antibacterial cytoplasmic membrane models composed of a mixture
      of palmitoyl-oleoyl-phosphatidyl-ethanolamine (POPE) and palmitoyl-oleoyl
      phosphatidylglycerol (POPG) lipid bilayers to provide a better understanding of
      their mode of action. In particular, the MD simulations performed at various
      concentrations of membrane-bound cyclic peptides reveal a novel type of mechanism
      in which the peptides first self-assemble at the membrane interface into
      amphipathic nanotubes. At high enough concentrations, coating of the membrane
      causes extrusion of lipids from the exposed bilayer leaflet, leading ultimately
      to a release of phospholipid micellar aggregates. Furthermore, the cyclic
      peptides also induce a drastic change in the lateral pressure profiles of the
      exposed leaflet, indicating a direct effect on the mechanical properties of the
      bilayer.

PMID- 20143884
TI  - Thermodynamic and hydrogen-bonding analyses of the interaction between model
      lipid bilayers.
AB  - This paper presents further analysis of a system containing two graphene plates
      with attached phosphatidylcholine lipid headgroups embedded in water, which
      models a lipid bilayer. Previously, we performed molecular dynamics simulations
      on this system, calculated the potential of mean force (PMF) between plates (Eun,
      C.; Berkowitz, M. L. J. Phys. Chem. B 2009, 113, 13222-13228), and also performed
      a structural analysis of water in the confined space between the plates. Here, we
      perform thermodynamic analysis of the PMF and, in addition to the previous
      analysis of water that considered density plots and the OH bond orientational
      profiles, we perform hydrogen bonding analysis of water. We show that the
      structural analysis of water is consistent with the thermodynamic results we
      obtained for the PMF.

PMID- 20143885
TI  - Dynamics of water in polyelectrolyte multilayers: restricted diffusion and cross
      relaxation.
AB  - The diffusion properties of water in polyelectrolyte multilayers (PEM) are
      investigated by pulsed field gradient diffusion NMR. The dependence of the mean
      square displacement on the observation time does not agree to Gaussian diffusion,
      suggesting restricted diffusion in a porous structure. However, the extraction of
      a pore size in a model of restricted diffusion yields a very large pore size of
      several micrometers. The additional influence of cross-relaxation of water and
      polymer spins is investigated in Goldman-Shen experiments. These demonstrate a
      strong influence of cross-relaxation rates on diffusion echo decays, such that
      pore sizes obtained from the model of restricted diffusion have to be corrected.
      Corrected pore sizes are about 4 microm and reflect the existence of domains of
      lower polymer density and thus faster water diffusion. These heterogeneities
      occur upon PEM preparation at high salt content for large layer numbers and are
      detected in the surface morphology, too.

PMID- 20143886
TI  - A framework for predicting surface areas in microporous coordination polymers.
AB  - A predictive tool termed the linker to metal cluster (LiMe) ratio is introduced
      as a method for understanding surface area in microporous coordination polymers
      (MCPs). Calibrated with geometric accessible surface area computations, the LiMe
      ratio uses molecular weight of building block components to indicate the maximum
      attainable surface area for a given linker and metal cluster combination. MOF-5
      and HKUST-1 are used as prototypical structures to analyze MCPs with octahedral
      M(4)O(CO(2)R)(6) and paddlewheel M(2)(CO(2)R)(4) metal clusters. Insight into the
      effects of linker size, geometry, number of coordinating groups, and framework
      interpenetration is revealed through the LiMe ratio analysis of various MCPs.
      Experimental surface area deviation provides indication that a material may
      suffer from incomplete guest removal, structural collapse, or interpenetration.
      Because minimal data input are required, the LiMe ratio surface area analysis is
      suggested as a quick method for experimental verification as well as a guide for
      the design of new materials.

PMID- 20143887
TI  - A new algorithm for the simulation of sodium dodecil sulfate two-dimensional
      polyacrylamide gel electrophoresis data sets.
AB  - A new algorithm for generating simulated sodium dodecil sulfate two-dimensional
      polyacrylamide gel electrophoresis (SDS 2D-PAGE) map images was developed. To
      choose the simulation strategy able to provide realistic 2D-PAGE maps, several
      parameters that characterize the statistical features of the images and data sets
      of images were taken into account, such as the distribution of size, intensity,
      and volume of the spots and their changes of position and volume along different
      replications of the same 2D-PAGE map. In this way, also the low reproducibility
      of replications of the same SDS 2D-PAGE maps was taken into account. The present
      algorithm can be usefully employed for the development of new classification
      and/or image analysis algorithms applied to bidimensional electrophoretic data
      sets, given the usually small number of experimental replications available.

PMID- 20143888
TI  - Voltammetric method for determining the trace moisture content of organic
      solvents based on hydrogen-bonding interactions with quinones.
AB  - Voltammetry experiments were performed on the natural quinone, vitamin K(1)
      (VK(1)), in a range of organic solvents of varying dielectric constant that are
      commonly used for electrochemical measurements [dimethyl sulfoxide (DMSO), N,N
      dimethylformamide (DMF), acetonitrile (MeCN), propionitrile (EtCN), butyronitrile
      (PrCN), 1,2-dichloroethane (DCE), dichloromethane (DCM), and 1,1,2,2
      tetrachloroethane (TCE)]. The water content of the solvents was accurately
      measured using Karl Fischer (KF) coulometric titrations, and the voltammetric
      data were used to estimate the degree of hydrogen-bonding interactions between
      the reduced forms of VK(1) and variable levels of water, thereby allowing a
      ranking of water-substrate interactions in the different solvents. The
      voltammetric data were analyzed based on interactions that occur between reduced
      forms of VK(1) and the water, the solvent, and the supporting electrolyte.
      Calibration data were obtained that are independent of the nature of the
      reference electrode and allow the water content of the solvents to be calculated
      by performing a single voltammetric scan in the presence of VK(1) and 0.2 M
      supporting electrolyte (Bu(4)NPF(6)).

PMID- 20143889
TI  - Development of electrogenerated chemiluminescence-based enzyme linked
      immunosorbent assay for sub-pM detection.
AB  - This paper reports the development and characterization of a highly sensitive
      enzyme linked immunosorbent assay realized by the electrogenerated
      chemiluminescence (ECL) detection of a thiol monolayer formed by an enzyme
      labeled antibody. We used two monoclonal anti tumor necrosis factor-alpha (TNF
      alpha) antibodies for a sandwich immunoassay. One was a capture antibody, and the
      other was a detection antibody labeled with an enzyme via an avidin-biotin
      interaction. Acetylcholinesterase was used as the labeling enzyme to convert
      acetylthiocholine to thiocholine. Then the thiocholine was collected on a gold
      electrode surface by gold-thiol binding. A bright and distinctive emission was
      observed at 1150 mV (vs Ag-AgCl) on the gold electrode with a thiocholine
      monolayer as a coreactant in the presence of tris(2,2'-bipyridyl)ruthenium
      complex. This method can greatly enhance the immunoassay signal since a large
      number of coreactant molecules can be generated by the enzymatic reaction, which
      is advantageous compared with a previously reported ECL based immunoassay that
      directly labels the detection antibody with a coreactant or luminophore. In
      addition, a surface accumulated coreactant is superior to the previously reported
      coreactant system in a bulk solution, because ECL emission occurs only very close
      to an electrode surface. As a result, high sensitivity and a low detection limit
      of 0.2 pM (3.4 pg/mL) TNF-alpha were achieved with excellent reproducibility by
      optimizing the conditions for the immuno-reaction, thiocholine accumulation, and
      ECL generation.

PMID- 20143890
TI  - Separation and detection of peroxynitrite using microchip electrophoresis with
      amperometric detection.
AB  - Peroxynitrite (ONOO(-)) is a highly reactive species implicated in the pathology
      of several cardiovascular and neurodegenerative diseases. It is generated in vivo
      by the diffusion-limited reaction of nitric oxide (NO(*)) and superoxide anion
      ((*)O(2)(-)) and is known to be produced during periods of inflammation.
      Detection of ONOO(-) is made difficult by its short half-life under physiological
      conditions (approximately 1 s). Here we report a method for the separation and
      detection of ONOO(-) from other electroactive species utilizing a microchip
      electrophoresis device incorporating an amperometric detection scheme. Microchip
      electrophoresis permits shorter separation times (approximately 25 s for ONOO(-))
      and higher temporal resolution than conventional capillary electrophoresis
      (several minutes). This faster analysis allows ONOO(-) to be detected before
      substantial degradation occurs, and the increased temporal resolution permits
      more accurate tracking of dynamic changes in chemical systems.

PMID- 20143891
TI  - Detection of volatile organic compounds in breath using thermal desorption
      electrospray ionization-ion mobility-mass spectrometry.
AB  - A thermal desorption unit has been interfaced to an electrospray ionization-ion
      mobility-time-of-flight mass spectrometer. The interface was evaluated using a
      mixture of six model volatile organic compounds which showed detection limits of
      <1 ng sample loaded onto a thermal desorption tube packed with Tenax, equivalent
      to sampled concentrations of 4 microg L(-1). Thermal desorption profiles were
      observed for all of the compounds, and ion mobility-mass spectrometry separations
      were used to resolve the probe compound responses from each other. The
      combination of temperature programmed thermal desorption and ion mobility
      improved the response of selected species against background ions. Analysis of
      breath samples resulted in the identification of breath metabolites, based on ion
      mobility and accurate mass measurement using siloxane peaks identified during the
      analysis as internal lockmasses.

PMID- 20143892
TI  - Identifying patients likely to have atopic dermatitis: development of a pilot
      algorithm.
AB  - BACKGROUND: A quick method to distinguish people who are predisposed to skin
      complaints would be useful in a variety of fields. Certain subgroups, such as
      people with atopic dermatitis, might be more susceptible to skin irritation than
      the typical consumer and may be more likely to report product-related complaints.
      OBJECTIVE: To develop a rapid, questionnaire-based algorithm to predict whether
      or not individuals who report skin complaints have atopic dermatitis. METHODS: A
      9-item questionnaire on self-perceived skin sensitivity and product categories
      reportedly associated with skin reactions was administered to two groups of
      patients from a dermatology clinic: one with clinically diagnosed, active atopic
      dermatitis (n = 25) and a control group of patients with dermatologic complaints
      unrelated to atopic dermatitis (n = 25). Questionnaire responses were correlated
      with the patients' clinical diagnoses in order to derive the minimum number of
      questions needed to best predict the patients' original diagnoses. RESULTS: We
      demonstrated that responses to a sequence of three targeted questions related to
      self-perceived skin sensitivity, preference for hypoallergenic products, and
      reactions to or avoidance of alpha-hydroxy acids were highly predictive of atopic
      dermatitis among a population of dermatology clinic patients. CONCLUSION: The
      predictive algorithm concept may be useful in postmarketing surveillance programs
      to rapidly assess the possible status of consumers who report frequent or
      persistent product-related complaints. Further refinement and validation of this
      concept is planned with samples drawn from the general population and from
      consumers who report skin complaints associated with personal products.

PMID- 20143893
TI  - Absence of inferior labial and lingual frenula in Ehlers-Danlos syndrome: a minor
      diagnostic criterion in French patients.
AB  - BACKGROUND: Ehlers-Danlos syndrome (EDS) is a heterogenous group of diseases that
      can be potentially life threatening in the vascular form. The diagnosis is mainly
      based on a clinical score including many items that demonstrate skin, mucosa,
      joint, and vessel involvement. The score is particularly helpful in hypermobile
      and classical forms but can be normal in the vascular type. The absence of the
      lingual and inferior labial frenula was reported to be a useful diagnostic tool
      in a series of 12 patients with classical and hypermobile EDS. However, two
      further reports have contested the value of this sign. OBJECTIVE: To determine
      the diagnostic value of the absence of inferior labial or lingual frenula in EDS.
      METHODS: Patients with EDS were prospectively recruited from November 2006 to
      April 2007 in a French tertiary center. Each patient was examined to check for
      the presence or absence of the oral frenula and matched with two controls seen
      from February to May 2007. RESULTS: Forty-three patients (ratio female/male of
      2.07 : 1, mean age 31 years, range 4-63 years), 4 with classical EDS, 19 with
      hypermobile EDS, and 20 with vascular-type EDS, were included and matched with 86
      controls. The sensitivity of the absence of the inferior labial frenulum was 42%
      (95% CI 27, 58) and for the lingual frenulum was 53.5% (95% CI 38, 69). The
      specificity was 99% (95% CI 94, 100) and 98% (95% CI 92, 100), respectively. In
      the vascular group, 13 of 20 patients were affected (sensitivity = 65% [95% CI
      41, 85]; specificity = 97% [95% CI 87, 100]; odds ratio = 72 [95% CI 8, 645]).
      Inter-observer agreement was excellent (kappa value 0.91). CONCLUSION: The
      absence of the inferior labial frenulum or lingual frenulum is a specific sign of
      EDS that can be easily checked by a physician. It can be helpful in the early
      diagnosis of the disease, including the vascular type, in affected families. It
      can also be helpful to distinguish between joint hypermobility syndrome and the
      hypermobile type of EDS in patients with joint hypermobility.

PMID- 20143894
TI  - The visual attractor illusion.
AB  - In many visual illusions, the perceived features of an object such as its size or
      orientation are influenced by nearby objects. In contrast, the presence of
      nearby, static objects often enhances the perceived spatial location of another
      object. Here we present a type of visual illusion in which the presence of a
      static object alters another object's perceived location. Participants localized
      the edge of a briefly presented and masked target object. Localization was
      accurate when the masked target was presented in isolation. However, when another
      nearby object was presented at the same time as the target, localization deviated
      toward the nearby object (the "attractor"). This "visual attractor illusion" was
      stronger when the attractor object was task-relevant rather than irrelevant and
      diminished as the experiment progressed, suggesting that it was modulated by
      attention. Visual transients also play an important role in the illusion, which
      depends on the sudden onset of the attractor object and backward masking of the
      target. We suggest that the brief appearance of an object (the attractor)
      distorts perceptual space and draws in the perceived location of a neighboring
      object. Alternatively, localization of a masked target may be weighted toward the
      position of a concurrently presented visual transient.

PMID- 20143895
TI  - Estimating perception of scene layout properties from global image features.
AB  - The relationship between image features and scene structure is central to the
      study of human visual perception and computer vision, but many of the specifics
      of real-world layout perception remain unknown. We do not know which image
      features are relevant to perceiving layout properties, or whether those features
      provide the same information for every type of image. Furthermore, we do not know
      the spatial resolutions required for perceiving different properties. This paper
      describes an experiment and a computational model that provides new insights on
      these issues. Humans perceive the global spatial layout properties such as
      dominant depth, openness, and perspective, from a single image. This work
      describes an algorithm that reliably predicts human layout judgments. This
      model's predictions are general, not specific to the observers it trained on.
      Analysis reveals that the optimal spatial resolutions for determining layout vary
      with the content of the space and the property being estimated. Openness is best
      estimated at high resolution, depth is best estimated at medium resolution, and
      perspective is best estimated at low resolution. Given the reliability and
      simplicity of estimating the global layout of real-world environments, this model
      could help resolve perceptual ambiguities encountered by more detailed scene
      reconstruction schemas.

PMID- 20143896
TI  - The role of co-circularity of local elements in texture perception.
AB  - The present study analyzes the effect of local pairwise orientation relations on
      the perception of textural structure. We have employed a new class of stochastic
      stimuli comprised of paired Gabor patches with a particular orientation
      difference (theta) and relative angular position (phi). We measured the threshold
      proportion of signal pairs for discriminating the target texture from a noise
      texture comprised of randomly oriented pairs. The results showed that observers
      were sensitive not only to textures containing pairs with curvilinear
      configurations such as lines and curves (phi = theta / 2), but also to their
      orthogonal configurations such as V shapes and parallels (phi = theta / 2 + 90).
      Both classes of configuration exhibit the property of co-circularity, a
      fundamental geometric feature of edges and contours in natural images. We also
      found higher sensitivity for textures made from orientation pairs with either
      large or small orientation differences. These results suggest that in addition to
      orientation difference, co-circularity plays a critical role in the perception of
      orientation-based textural structure.

PMID- 20143897
TI  - Parafoveal color discrimination: a chromaticity locus of enhanced discrimination.
AB  - Are boundaries between color categories associated with enhanced discrimination?
      In the present experiments, chromatic thresholds were obtained for
      discriminations along lines orthogonal to the yellow-blue axis of color space.
      The targets were parafoveal and thresholds were measured with a spatial two
      alternative forced choice. In interleaved experimental runs, we also obtained
      empirical estimates of the subjective yellow-blue line by asking observers to
      categorize colors as reddish or greenish. Both types of measurement were made in
      the presence of a steady background that was metameric to equal-energy white. In
      a limited region from desaturated yellow to desaturated blue, an enhanced
      discrimination is found near the subjective transition between reddish and
      greenish hues. This line of optimal discrimination is not aligned with either of
      the cardinal axes of color space: In a MacLeod-Boynton chromaticity diagram, it
      runs obliquely with negative slope.

PMID- 20143898
TI  - Cue combination for 3D location judgements.
AB  - Cue combination rules have often been applied to the perception of surface shape
      but not to judgements of object location. Here, we used immersive virtual reality
      to explore the relationship between different cues to distance. Participants
      viewed a virtual scene and judged the change in distance of an object presented
      in two intervals, where the scene changed in size between intervals (by a factor
      of between 0.25 and 4). We measured thresholds for detecting a change in object
      distance when there were only 'physical' (stereo and motion parallax) or 'texture
      based' cues (independent of the scale of the scene) and used these to predict
      biases in a distance matching task. Under a range of conditions, in which the
      viewing distance and position of the target relative to other objects was varied,
      the ratio of 'physical' to 'texture-based' thresholds was a good predictor of
      biases in the distance matching task. The cue combination approach, which
      successfully accounts for our data, relies on quite different principles from
      those underlying traditional models of 3D reconstruction.

PMID- 20143900
TI  - The face-in-the-crowd effect: when angry faces are just cross(es).
AB  - A common theme running through much of the visual recognition literature is that
      faces are special. Many studies now describe evidence for the idea that faces are
      processed in a dedicated center in cortex. Studies have also argued for the
      presence of evolutionarily expedient pathways dedicated to the processing of
      certain facial expressions. Evidence for this proposal comes largely from visual
      search tasks which have established that threatening expressions are more rapidly
      detected than other expressions: the 'face-in-the-crowd effect'. One open
      criticism of this effect is that it may be due to low-level visual artifacts,
      rather than biological preparedness. One attempt at controlling low-level
      differences has been to use schematic line-drawing versions of faces. This study
      aimed to discover if there might be alternative issues with schematic stimuli.
      The first study replicated the face-in-the-crowd threat advantage for schematic
      faces, but also measured a comparable effect using stimuli comprised of obliquely
      oriented lines. Similar results were achieved with these stimuli rotated, which
      had the effect of removing any residual resemblance to a face. The results
      suggest that low-level features probably underlie the face-in-the-crowd effect
      described for schematic face images, thereby undermining evidence for a search
      advantage for specific facial expressions.

PMID- 20143899
TI  - Natural cross-modal mappings between visual and auditory features.
AB  - The brain may combine information from different sense modalities to enhance the
      speed and accuracy of detection of objects and events, and the choice of
      appropriate responses. There is mounting evidence that perceptual experiences
      that appear to be modality-specific are also influenced by activity from other
      sensory modalities, even in the absence of awareness of this interaction. In a
      series of speeded classification tasks, we found spontaneous mappings between the
      auditory feature of pitch and the visual features of vertical location, size, and
      spatial frequency but not contrast. By dissociating the task variables from the
      features that were cross-modally related, we find that the interactions happen in
      an automatic fashion and are possibly located at the perceptual level.

PMID- 20143901
TI  - The reference frame of the tilt aftereffect.
AB  - Perceptual aftereffects provide a sensitive tool to investigate the influence of
      eye and head position on visual processing. There have been recent indications
      that the TAE is remapped around the time of a saccade to remain aligned to the
      adapting location in the world. Here, we investigate the spatial frame of
      reference of the TAE by independently manipulating retinal position, gaze
      orientation, and head orientation between adaptation and test. The results show
      that the critical factor in the TAE is the correspondence between the adaptation
      and test locations in a retinotopic frame of reference, whereas world- and head
      centric frames of reference do not play a significant role. Our results confirm
      that adaptation to orientation takes place at retinotopic levels of visual
      processing. We suggest that the remapping process that plays a role in visual
      stability does not transfer feature gain information around the time of eye (or
      head) movements.

PMID- 20143902
TI  - A biologically plausible model of human shape symmetry perception.
AB  - Symmetry is usually computationally expensive to encode reliably, and yet it is
      relatively effortless to perceive. Here, we extend F. J. A. M. Poirier and H. R.
      Wilson's (2006) model for shape perception to account for H. R. Wilson and F.
      Wilkinson's (2002) data on shape symmetry. Because the model already accounts for
      shape perception, only minimal neural circuitry is required to enable it to
      encode shape symmetry as well. The model is composed of three main parts: (1)
      recovery of object position using large-scale non-Fourier V4-like concentric
      units that respond at the center of concentric contour segments across
      orientations, (2) around that recovered object center, curvature mechanisms
      combine multiplicatively the responses of oriented filters to encode object
      centric local shape information, with a preference for convexities, and (3)
      object-centric symmetry mechanisms. Model and human performances are comparable
      for symmetry perception of shapes. Moreover, with some improvement of edge
      recovery, the model can encode symmetry axes in natural images such as faces.

PMID- 20143903
TI  - Disparity sensitivity in man and owl: Psychophysical evidence for equivalent
      perception of shape-from-stereo.
AB  - The perception of shape-from-stereo is best characterized by the spatial
      disparity-contrast sensitivity function (DSF). This is the stereo analogue of the
      well-known luminance-contrast sensitivity function (CSF). In principle, the DSF
      and CSF portray a visual system's ability to detect spatial modulation as
      specified by changes in binocular disparity and luminance, respectively. In
      humans, less fine detail is visible in the stereo domain than is possible in the
      luminance domain. Here, we characterize for the first time the DSF in a non-human
      species, viz. the barn owl. At the same time, we re-examined the human DSF with
      identical apparatus and methods to directly compare between two vertebrate
      species that evolved stereovision independently. We discovered a close
      relationship between the owl and human ability to detect shape-from-stereo. In
      particular, the shift in absolute position between the human and owl DSF, as
      measured here, closely corresponds to the shift in absolute position between
      their respective CSFs, as known from the literature. In conclusion, our study
      establishes unprecedented experimental proof of a striking similarity in the
      prowess of humans and owls to achieve shape-from-stereo.

PMID- 20143904
TI  - The Muller-Lyer illusion: investigation of a center of gravity effect on the
      amplitudes of saccades.
AB  - Previous research has compared the effects of visual illusions on perception with
      their effects on action to investigate if the action system and the perceptual
      system use different or common codes. Appropriate conclusions based on this
      comparison rely on effects that reflect the internal parameter estimates of the
      action and of the perceptual system. We investigated an additional factor that
      can possibly change the amplitudes of saccades along the Muller-Lyer illusion,
      the center of gravity effect. It refers to the finding that the endpoints of
      saccades can be diverted from the target point in the direction of the center of
      gravity of a stimulus configuration. We measured the perceptual (adjustment
      method) and the action effects (amplitudes of saccades) of the illusion. In
      addition, we let subjects carry out saccades along Muller-Lyer figures and a
      neutral figure that appeared to have the same size (but differed in actual
      sizes). The amplitudes of saccades differed for these figures. This was
      interpreted as evidence for a center of gravity effect. Its quantification
      allowed a correction of the action effect, which was then remarkably similar to
      the perceptual effect. Our results are in agreement with the notion of a common
      internal representation for perception and action.

PMID- 20143905
TI  - Effects of task and coordinate frame of attention in area 7a of the primate
      posterior parietal cortex.
AB  - The activity of neurons in the primate posterior parietal cortex reflects the
      location of visual stimuli relative to the eye, body, and world, and is modulated
      by selective attention and task rules. It is not known however how these effects
      interact with each other. To address this question, we recorded neuronal activity
      from area 7a of monkeys trained to perform two variants of a delayed match-to
      sample task. The monkeys attended a spatial location defined in either
      spatiotopic (world-centered) or retinotopic (eye-centered) coordinates. We found
      neuronal responses to be remarkably plastic depending on the task. In contrast to
      previous studies using the simple version of the delayed match-to-sample task, we
      discovered that after training in a task where the locus of attention shifted
      during the trial, neural responses were typically enhanced for a match stimulus.
      Our results further revealed that responses were mostly enhanced for stimuli
      matching in spatiotopic coordinates, although the proportion of neurons modulated
      by either coordinate frame was influenced by the behavioral task executed.

PMID- 20143906
TI  - Initiation of the optokinetic response (OKR) in mice.
AB  - To study the initial part of the mouse optokinetic response, OKR (approximately
      500 ms from the onset of visual stimulus motion), we recorded the ocular response
      to a vertical sinusoidal grating moving at a constant velocity. We found that the
      magnitude of the response monotonically increased as the stimulus contrast
      increased. The response showed a narrow band-pass property for the spatiotemporal
      frequency, with the largest sustained response observed at 0.125 cycle/deg and
      1.5 Hz. We also found that temporal frequencies higher than 1.5 Hz elicited
      transient increase in the eye velocity, but weak or no sustained eye movements.
      Thus the initial OKR in mice is characterized by the spatiotemporal frequency of
      the visual stimuli. Our results suggest that the initial OKR contains two
      components: a transient that diminishes within approximately 200 ms, and a tonic
      that is maintained for more than 400 ms, and that the initial part of the OKR in
      mice is an appropriate measurement parameter for studies of the visual and motor
      systems, like ocular following response (OFR) in primates.

PMID- 20143907
TI  - Lengthy suppression from similar stimuli during rapid serial visual presentation.
AB  - The stimulus at any point in the visual field is rarely static during normal
      viewing: observer and object movement conspire to produce a continually changing
      series of stimuli. Our aim was to study both the short- and long-term
      interactions between responses to a series of stimuli presented at a single
      visual location. We used rapid serial visual presentation (RSVP) in which the
      stimuli were randomly oriented gratings delivered at the rate of 30 per second.
      Human subjects pressed a key whenever they saw a target orientation, for example
      horizontal. The results were analyzed by finding two orientations before each key
      press. The first preceded the key-press by the reaction time, and the second
      preceded the first by an interval of variable duration. There were two main
      findings. First, the subject was more likely to press the key when the target was
      immediately preceded by a grating of similar orientation. This facilitation
      presumably results from the summation of sub-threshold inputs. Second, a key
      press was reduced in probability when a target orientation was preceded by a
      similar orientation with an interstimulus interval of 100-400 ms. The time course
      of this suppression is similar to that seen in attentional blink experiments.

PMID- 20143908
TI  - Inverting faces elicits sensitivity to race on the N170 component: a cross
      cultural study.
AB  - Human beings are natural experts at processing faces, with some notable
      exceptions. Same-race faces are better recognized than other-race faces: the so
      called other-race effect (ORE). Inverting faces impairs recognition more than for
      any other inverted visual object: the so-called face inversion effect (FIE).
      Interestingly, the FIE is stronger for same- compared to other-race faces. At the
      electrophysiological level, inverted faces elicit consistently delayed and often
      larger N170 compared to upright faces. However, whether the N170 component is
      sensitive to race is still a matter of ongoing debate. Here we investigated the
      N170 sensitivity to race in the framework of the FIE. We recorded EEG from
      Western Caucasian and East Asian observers while presented with Western
      Caucasian, East Asian and African American faces in upright and inverted
      orientations. To control for potential confounds in the EEG signal that might be
      evoked by the intrinsic and salient differences in the low-level properties of
      faces from different races, we normalized their amplitude-spectra, luminance and
      contrast. No differences on the N170 were observed for upright faces. Critically,
      inverted same-race faces lead to greater recognition impairment and elicited
      larger N170 amplitudes compared to inverted other-race faces. Our results
      indicate a finer-grained neural tuning for same-race faces at early stages of
      processing in both groups of observers.

PMID- 20143909
TI  - Genetic testing and biomarkers in the new decade.

PMID- 20143910
TI  - The mitochondrial DNA variant 16189T>C is associated with coronary artery disease
      and myocardial infarction in Saudi Arabs.
AB  - By virtue of the functional role of the mitochondrion in energy and reactive
      oxygen species production, mutations in mitochondrial DNA (mtDNA) are potential
      candidates for cardiovascular-related disorders. Further, the mtDNA is extremely
      polymorphic and several diagnostic single-nucleotide polymorphisms have been used
      to assort sequences into haplogroups with defined continental and regional
      ranges. However, the relevance of these haplogroups and mutations with respect to
      coronary artery disease (CAD) susceptibility remains unclear. In this study, we
      evaluated the role of the 16189T>C variants and mtDNA haplogroups as predisposing
      factors for CAD in 669 Saudi patients with angiographically established disease
      compared with 258 disease-free controls. The 16189T>C was associated with CAD
      (1.524 [1.076-2.159]; p = 0.017). However, this association was influenced by age
      as well as the presence of myocardial infarction and hypertension. Among the
      haplogroups, only the N1c showed a borderline protective relationship (p = 0.074)
      with CAD as an independent risk factor. This association turned significant in
      the total sample (0.176 [0.042-0.736]; p = 0.017) and in the <50-year age group
      (0.075 [0.008-0.743]; p = 0.027), when included as a possible confounding factor.
      Our results suggested that the impact of mtDNA polymorphism on CAD manifestation
      is influenced by important confounders, particularly the presence of myocardial
      infarction, hypertension, and age.

PMID- 20143911
TI  - Prevalence of mitochondrial tRNA gene mutations and their association with
      specific clinical phenotypes in patients with type 2 diabetes mellitus of
      Coimbatore.
AB  - The association of mitochondrial DNA mutation with type 2 diabetes mellitus
      (T2DM) is well established. In this study we aimed to assess the frequency of
      A3243G, A8296G, and other mitochondrial mutations with reference to clinical
      features in the diabetic population of Coimbatore, India. The study group
      included 150 patients (89 women and 61 men) with T2DM, whereas the control group
      included 100 nondiabetic people (59 women and 41 men). Genotyping was done by
      polymerase chain reaction followed by single-strand confirmation polymorphism
      method. A3243G and A8296G mutations were found to be prevalent in patients with
      T2DM when compared with the control group. The A3243G mutation was found in two
      patients, and both these patients showed similar clinical characteristics, thus
      representing a putative clinical subtype. A8296G mutation was detected in one
      patient. The same mutation was shared with his mother who was diagnosed to have
      diabetes mellitus (DM) with neuromuscular disorder. The siblings of the patient
      did not show any symptoms of DM. Lipid profile and urea and creatinine levels
      were found to be significantly high (10% and 0.064%) in patients with T2DM
      compared with control subjects. We concluded that the identification of these
      mitochondrial point mutations indicates a new genetic predisposition of DM in
      Coimbatore population.

PMID- 20143912
TI  - Clinical, cytogenetic, and molecular characterization of a girl with some
      clinical features of Down syndrome resulting from a pure partial trisomy 21q22.11
      qter due to a de novo intrachromosomal duplication.
AB  - We report a girl with a de novo pure partial trisomy 21 with some clinical
      features of Down syndrome. The girl patient presented a flat broad face,
      brachycephaly, and a flat nasal bridge. She also had upwardly slanted palpebral
      fissures, epicanthal folds, blepharitis, brushfield spots, and strabismus. Her
      mouth was wide with downturned corners, prominent lower lip, narrow and furrowed
      tongue, and short palate. G-banded chromosomal analysis of metaphases in cells
      from both skin and blood showed a 46,XX karyotype with additional chromosomal
      material on the distal short arm of one chromosome 21. Parental chromosomes were
      normal. Molecular analyses with the short-tandem-repeat (STR) marker D21S2039
      (interferon-alpha/beta receptor [IFNAR]) (21q22.1) showed a triallelic pattern.
      Subtelomeric fluorescent in situ hybridization (FISH) analyses, LSI 13
      (retinoblastoma 1 [RB1])/LSI 21(21q22.13-q22.2), and whole chromosome painting
      probes specific for chromosome 21 showed trisomy for the segment 21q22.13-21q22.2
      due to a de novo intrachromosomal duplication. A 500K SNP microarray analysis was
      then performed and revealed a 13-Mb duplication of 21q22.11-qter. This duplicated
      material had been translocated onto the end of the "p" arm of one of the
      chromosome 21s. The karyotype was provisionally defined as 46,XX,add(21)(p12).ish
      der (21)t(21;21)(p12;q22.11)(WCP21q+,PCP21q++,D215259/D21S341/D21S342++)dn. At
      the age of 4 years and 10 months, a comprehensive psychological examination was
      performed and the diagnostic criteria for mental retardation were not fulfilled.
      In comparison with previously published cases of pure partial trisomy 21, this is
      a rare finding. Additional studies of such rare patients should aid in the study
      of the pathogenesis of Down syndrome.

PMID- 20143913
TI  - Large deletion involving exon 5 of the arylsulfatase B gene caused apparent
      homozygosity in a mucopolysaccharidosis type VI patient.
AB  - Apparent homozygosity for the mutation p.R315X present on exon 5 of the
      arylsulfatase B (ARSB) gene in a mucopolysaccharidosis type VI patient was solved
      in this study by further testing for a second mutation. Patient cDNA analysis
      revealed that the entire exon 5 of the ARSB gene was lacking; this new mutation
      was identified as c.899-1142del. As the genomic DNA sequencing excluded the
      presence of splicing mutations, polymerase chain reaction analysis was performed
      for polymorphisms listed in the NCBI SNP database for the ARSB gene. This allowed
      the mutation at the genomic DNA level to be identified as g.99367-102002del; this
      gross deletion, involving the entire exon 5 of the gene and parts of introns 4
      and 5 led to a frameshift starting at amino acid 300 and resulting in a protein
      with 39% amino acids different from the normal enzyme. We stress that extensive
      DNA analysis needs to be performed in case of apparent homozygosity to avoid
      potential errors in genetic counseling.

PMID- 20143914
TI  - Overexpression of human CAP10-like protein 46 KD in T-acute lymphoblastic
      leukemia and acute myelogenous leukemia.
AB  - AIMS: We earlier identified a novel gene human CAP10-like protein 46 KD (hCLP46)
      from human acute myelogenous leukemia (AML) transformed from myelodysplastic
      syndrome CD34(+) cells, but the function of this gene remains unclear. In this
      study, a real-time polymerase chain reaction-based assay was developed to
      quantify expression of hCLP46 in the peripheral blood of AML and T-acute
      lymphoblastic leukemia (T-ALL) primary samples and in six leukemic cell lines.
      Also, we investigated expression of CDKN2A/B and the apoptosis in U937 cells when
      hCLP46 is downregulated in vitro. RESULTS: Our findings showed that hCLP46 was
      overexpressed in AML, T-ALL, and the leukemic cell lines. Suppressing hCLP46
      overexpression had no effect on expression of CDKN2A/B and apoptosis of U937
      cells. CONCLUSION: Considering that hCLP46 has the capability of modifying the
      Notch pathway, our finding adds weight to the importance of Notch signaling in
      hematopoiesis and suggests that overexpression of hCLP46 might be an early event
      in the pathogenesis of AML and T-ALL.

PMID- 20143915
TI  - Lymphatic Biology in Health and Disease: an NIH perspective.

PMID- 20143916
TI  - Lymphatic research: past, present, and future.

PMID- 20143917
TI  - Non-peptide small molecule regulators of lymphangiogenesis.
AB  - Adrenomedullin (AM) and gastrin releasing peptide (GRP) are neuroendocrine
      peptides that have been previously implicated as regulators of angiogenesis and
      lymphangiogenesis. Using an immortalized human dermal microvascular lymphatic
      endothelial cell line stably transfected with red fluorescent protein (LEC/RFP),
      we demonstrate the ability of AM and GRP to augment tube formation complexity of
      this target cell in a dose-dependent manner. Maximum tube density was initiated
      at 1 nM for both peptides, and as concentrations exceeded 10 nM a decrease in
      tube formation was noted, hence following a classic rise/fall biological response
      curve. In addition, we show that appropriate small molecule mimetics to
      neutralizing monoclonal antibodies of AM or GRP, at 1 microM concentration, can
      function to either inhibit (antagonist) or enhance (super agonist) peptide
      induced tube formation of LEC/RFP. Our small molecule reagents by themselves have
      no activity, but in the presence of their respective peptides can mediate a
      positive or negative response, hence the super agonist designation. These
      compounds represent new regulatory drugs of the lymphatic system with possible
      patient application in the clinical management of edema and metastatic disease.

PMID- 20143918
TI  - Lymphatics in idiopathic pulmonary fibrosis: new insights into an old disease.
AB  - The lymphatic vasculature plays a key role in tissue homeostasis and immune
      surveillance. There is mounting evidence of a role for the lymphatic circulation
      and for newly formed lymphatic vessels in the pathogenesis of lung disease.
      Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating lung
      disease. In IPF, the lung parenchyma undergoes extensive remodeling. This review
      focuses on the current knowledge and understanding of the pathogenesis of IPF,
      and recent evidence of the involvement of lymphangiogenesis in lung injury and
      repair and the molecular and cellular pathways leading to the development of
      lymphatic vasculature.

PMID- 20143919
TI  - New approaches to lymphatic imaging.
AB  - Accurate imaging of the lymphatic system can aid in cancer staging, optimize
      surgical procedures to reduce lymphedema, and may one day be a means of
      delivering intralymphatic therapy. The Sentinel Lymph Node (SLN) concept has been
      pivotal in driving new imaging techniques. Metastasis to a SLN is a critical
      indicator of advanced disease. However, presently, few tools are available for
      imaging the lymphatics, and even fewer are available for locating the SLN for
      biopsy. Recently, new macromolecular agents, including gadolinium-labeled
      dendrimers, fluorescent quantum dots, and fluorescently-labeled immunoglobins,
      have been used to image the lymphatics and SLN with MRI and optical techniques,
      and new fluorescent nanoparticles such as upconverting nanocrystals are potential
      future agents. Additionally, multi-modality probes combining two modalities such
      as optical/MR dendrimers have been designed to provide both preoperative imaging,
      and intraoperative guidance during lymph node resections. These probes can map
      the lymphatic system for maximal therapeutic benefit while minimizing
      complications such as lymphedema. Advances in the understanding of the molecular
      mechanisms of lymphangiogenesis and lymphatic spread of tumors offer the
      opportunity for more targeted imaging of the lymphatic system. Additionally,
      these imaging agents could be used as powerful research tools for tracking
      immunological cells and monitoring the immune response as well as providing the
      means to deliver lymphatic-targeted therapies. The future holds great promise for
      the translation of these methods to the clinic.

PMID- 20143920
TI  - Lymphatics in human lymphatic filariasis: in vitro models of parasite-induced
      lymphatic remodeling.
AB  - Lymphatic filariasis characterized by the dysfunction of the lymphatics can lead
      to severe (and often) irreversible lymphedema and elephantiasis. Decades of
      research in the field shows that the establishment of the adult parasites in the
      lymphatics triggers a cascade of events that ultimately results in tissue
      scarring and fibrosis. In this minireview, we focus on the studies addressing the
      mechanisms underlying the parasite-induced lymphatic dilatation that suggests
      parasite-induced lymphatic remodeling and lymphangiogenesis may be the prelude
      towards developing chronic and irreversible filarial pathology.

PMID- 20143921
TI  - Involvement of lymphatics in lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM), a rare multisystem disease, occurs primarily in
      women, with cystic destruction of the lungs, abdominal tumors, and involvement of
      the axial lymphatics in the thorax and abdomen. To understand the pathogenesis of
      LAM, we initiated a longitudinal study of patients with LAM; over 500 patients
      have been enrolled. LAM results from the proliferation of a neoplastic cell (LAM
      cell), which has mutations in the tuberous sclerosis complex (TSC) genes, TSC1 or
      TSC2. Consistent with their metastatic behavior, LAM cells were isolated from
      blood, urine, and chylous effusions. Surface proteins on LAM cells include those
      found on metastatic cells and those involved in cell migration. In the lung, LAM
      cells are found clustered in nodules, which appear in the walls of the cysts, and
      in the interstitium. LAM lung nodules are traversed by slit-like vascular
      structures, with lining cells showing reactivity with antibodies against
      components of lymphatic endothelial cells. The axial lymphatics appear to be
      infiltrated by LAM cells, which may result in obstruction and formation of chyle
      filled lymphangioleiomyomas. LAM cell clusters have been isolated from chylous
      pleural effusions, and it is hypothesized that these clusters may be responsible
      for metastatic spread of LAM cells via lymphatic vessels. Consistent with a
      lymphangiogenic process, levels of VEGF-D, a lymphangiogenic factor, were higher
      in sera of patients with LAM and lymphatic involvement (i.e.,
      lymphangioleiomyoma, adenopathy) than in healthy volunteers or LAM patients with
      cystic disease limited to the lung. These findings are consistent with an
      important function for lymphangiogenesis in LAM.

PMID- 20143922
TI  - Lymphatic endothelial cells adapt their barrier function in response to changes
      in shear stress.
AB  - BACKGROUND: Lymphatic endothelial cells form an important barrier necessary for
      normal lymph formation and propulsion. However, little is known about how
      physical forces within lymphatic vessels affect endothelial barrier function. The
      purpose of this study was to characterize how laminar flow affects lymphatic
      endothelial barrier function and to test whether endothelial cells respond to
      flow changes by activating the intracellular actin cytoskeleton to enhance
      barrier function. METHODS AND RESULTS: Cultured adult human dermal microlymphatic
      endothelial cells (HMLEC-d) were grown on small gold electrodes arranged within a
      flow channel, and transendothelial electrical resistance (TER), an index of
      barrier function, was determined. Laminar flow was applied to the cells at a
      baseline shear stress of 0.5 dynes/cm(2), and was increased to 2.5, 5.0, or 9.0
      dynes/cm(2), causing a magnitude-dependent increase in barrier function that was
      reversed 30 min later when the shear stress was returned to baseline. This
      response was abolished by blockade of actin dynamics with 10 microM phalloidin,
      and significantly inhibited by blockade of Rac1 activity with 50 microM NSC23766.
      Blockade of protein kinase A (10 microM H-89) did not inhibit the response.
      Mathematical modeling based on our impedance data showed that the flow-induced
      changes in TER were primarily due to altered current flow between cells and not
      beneath cells. CONCLUSIONS: These results suggest that lymphatic endothelial
      cells dynamically alter their morphology and barrier function in response to
      changes in shear stress by a mechanism dependent upon Rac1-mediated actin
      dynamics.

PMID- 20143923
TI  - Topography of accumulation of stagnant lymph and tissue fluid in soft tissues of
      human lymphedematous lower limbs.
AB  - BACKGROUND: The knowledge of where does excess tissue fluid accumulate in
      obstructive lymphedema is indispensable for rational physical therapy. However,
      it has so far been limited to that obtained from lymphoscintigraphic,
      ultrasonographic, and MR images. None of these modalities provide composite
      pictures of dilated lymphatics and expanded tissue space in dermis, subcutis, and
      muscles. So far, only anatomical dissection and histological processing of biopsy
      material can visualize the tissue lymphatic network and the sites of accumulation
      of the excess of mobile tissue fluid. METHODS AND RESULTS: We visualized the
      "tissue fluid and lymph" space in skin and subcutaneous tissue of foot, calf, and
      thigh in various stages of lymphedema in specimens obtained during lymphatic
      microsurgical procedures or tissue debulking, using special staining techniques.
      The volume of accumulated fluid was calculated from the densitometric data of
      stained tissue sections. We found that lymph was present only in the subepidermal
      lymphatics, whereas the collecting trunks were obliterated in most cases. Mobile
      tissue fluid accumulated in the spontaneously formed spaces in the subcutaneous
      tissue, around small veins and above and underneath muscular fascia. Deformation
      of subcutaneous tissue by free fluid led to formation of interconnecting
      channels. The volume of subcutaneous free fluid ranged around 50% of total tissue
      volume and there were no significant differences in various stages of lymphedema.
      This could be explained by the presence of thick layers of subcutaneous fat
      tissue even in the most advanced stage of lymphedema. CONCLUSIONS: In lymphedema
      caused by obliteration of collecting trunks, lymph is present only in the
      subepidermal lymphatics, whereas the bulk of stagnant tissue fluid accumulates in
      the subcutaneous tissue and above and beneath muscular fascia. These findings
      should be useful for designing pneumatic devices for limb massage as well as for
      rational manual lymphatic drainage in terms of sites of massage and level of
      applied external pressures.

PMID- 20143926
TI  - Translational studies in anterior cruciate ligament repair.
AB  - Translational research, which can be explained as the principle of combining
      advances in both basic research and clinical understanding in a bedside-to-bench
      to-bedside approach, has become one of the central themes of present-day medical
      research. One orthopedic problem that has strongly benefited from such an
      approach is tissue-engineering-enhanced primary repair of the anterior cruciate
      ligament. Recent years have shown a clearer definition of the clinical problem
      and established an underlying mechanistic cause of the incapacity of the anterior
      cruciate ligament to heal-the premature loss of provisional scaffold in the wound
      site. These clinical findings were then translated into a research objective,
      namely, to replace the missing scaffold with a biomaterial with appropriate
      structural and bio-stimulatory characteristics. Subsequently, a tissue
      engineering-based treatment using a collagen-platelet composite was developed and
      tested in vitro. After proofing the efficacy of this new treatment in the
      laboratory, it was translated into a potential clinical application, which showed
      highly successful results in structural integrity and biomechanical capacity in
      large animal testing. This approach of defining the scientific mechanism
      underlying a clinical observation and then using that information to design new
      therapies is but one example of how translational research in tissue engineering
      can help define and develop new treatments for challenging problems faced by
      patients.

PMID- 20143929
TI  - Videourology: an historical perspective and a view to the future. Interview by
      Ralph V. Clayman.

PMID- 20143927
TI  - Direct gene therapy for bone regeneration: gene delivery, animal models, and
      outcome measures.
AB  - While various problems with bone healing remain, the greatest clinical change is
      the absence of an effective approach to manage large segmental defects in limbs
      and craniofacial bones caused by trauma or cancer. Thus, nontraditional forms of
      medicine, such as gene therapy, have been investigated as a potential solution.
      The use of osteogenic genes has shown great potential in bone regeneration and
      fracture healing. Several methods for gene delivery to the fracture site have
      been described. The majority of them include a cellular component as the carrying
      vector, an approach known as cell-mediated gene therapy. Yet, the complexity
      involved with cell isolation and culture emphasizes the advantages of direct gene
      delivery as an alternative strategy. Here we review the various approaches of
      direct gene delivery for bone repair, the choice of animal models, and the
      various outcome measures required to evaluate the efficiency and safety of each
      technique. Special emphasis is given to noninvasive, quantitative, in vivo
      monitoring of gene expression and biodistribution in live animals. Research
      efforts should aim at inducing a transient, localized osteogenic gene expression
      within a fracture site to generate an effective therapeutic approach that would
      eventually lead to clinical use.

PMID- 20143930
TI  - Office-based transurethral resection of multiple bladder tumors using blue dye
      mixed local anesthesia: a descriptive cohort study.
AB  - OBJECTIVE: Hospitalization and general anesthesia to perform transurethral
      resection of bladder tumors (BTs) may not be necessary for small recurrent BTs.
      We developed a new outpatient procedure. PATIENTS AND METHODS: Patients with
      recurrent small tumors who had previously undergone transurethral resection of
      BTs for low-grade, noninvasive BTs were eligible for this new procedure. Between
      July 2005 and 2007, 21 surgeries were performed on 11 patients. The patients'
      mean age was 65.6 years. The bladder was dilated with CO(2) using a 15.5F
      flexible cystoscope. Blue dye-mixed local anesthetic (2% xylocaine:indigo carmine
      8:2) was injected into the tumor base. The tumor was resected using electric
      current via a hot cup. Patients went home without an indwelling catheter if there
      was no hematuria in the first urination after the procedure. RESULTS: Fifteen
      surgeries revealed one tumor, two had two tumors, two had three tumors, and two
      had six tumors. No complications requiring hospitalization occurred. Each
      resected specimen included a submucosal layer that allowed differentiation
      between pTa and pT1. No thermal degeneration was apparent in the resected stumps
      on pathological examination. Sixteen cases were urothelial carcinoma, and five
      cases were benign. Fifteen of the malignancies were noninvasive/low-grade tumors,
      but one case was microinvasive/high grade (G3pT1). During follow-up (mean, 8.8
      months) recurrence in the bladder was found in 47%, but there was no orthotopic
      recurrence in the tumor-resected region. CONCLUSION: Our method allows safe
      resection of multiple recurrent BTs on an outpatient basis. This approach is a
      promising method for pathological diagnosis and favorable local control.

PMID- 20143935
TI  - Beta galactosidases and their potential applications: a review.
AB  - Beta galactosidases have been obtained from microorganisms such as fungi,
      bacteria and yeasts; plants, animals cells, and from recombinant sources. The
      enzyme has two main applications; the removal of lactose from milk products for
      lactose intolerant people and the production of galactosylated products. In order
      to increase their stability, reusability, and use in continuous reactors, these
      enzymes have been immobilized on both organic and inorganic support via
      adsorption, covalent attachment, chemical aggregation, microencapsulation, and
      entrapment. Free and immobilized preparations of beta galactosidases have been
      exploited in various applications such as industrial, biotechnological, medical,
      analytical, and in different other applications. beta galactosidase is widely
      used in food industry to improve sweetness, solubility, flavor, and digestibility
      of dairy products. Immobilized beta galactosidases are employed for the
      continuous hydrolysis of lactose from whey and milk in a number of reactors such
      as hollow fiber reactors, tapered column reactors, packed bed reactors, fluidized
      bed reactors etc.

PMID- 20143936
TI  - On the road to systems biology of host-pathogen interactions.

PMID- 20143937
TI  - Technology-driven research will dominate hypothesis-driven research: the future
      of microbiology.

PMID- 20143940
TI  - An approach to characterize the membrane proteome of Candida albicans.

PMID- 20143938
TI  - What is systems biology?

PMID- 20143941
TI  - Metabolomics: towards understanding host-microbe interactions.
AB  - Metabolomics employs an array of analytical techniques, including high-resolution
      nuclear magnetic resonance spectroscopy and mass spectrometry, to simultaneously
      analyze hundreds to thousands of small-molecule metabolites in biological
      samples. In conjunction with chemoinformatics and bioinformatics tools,
      metabolomics enables comprehensive characterization of the metabolic phenotypes
      (metabotypes) of the human, and other mammalian, hosts that have co-evolved with
      a large number of diverse commensal microbes, especially in the intestinal tract.
      Correlation of the metabotypes with the microbial profiles derived from culture
      independent molecular techniques is increasingly helping to decipher inherent and
      intimate host-microbe relationships. This integrated, systems biology approach is
      improving our understanding of the molecular mechanisms underlying multilevel
      host-microbe interactions, and promises to elucidate the etiologies of human
      disorders resulting from unfavorable human-microbial associations, including
      enteric infections.

PMID- 20143942
TI  - Use of logic theory in understanding regulatory pathway signaling in response to
      infection.
AB  - Biological pathways link the molecular and cellular levels of biological activity
      and perform complex information processing seamlessly. Systems biology aims to
      combine an understanding of the cause-effect relationships of each individual
      interaction to build an understanding of the function of whole pathways.
      Therapies that target the 'host' biological processes in infectious diseases are
      often limited to the use of vaccines and biologics rather than small molecules.
      The development of host drug targets for small molecules is constrained by a
      limited knowledge of the underlying role of each target, particularly its
      potential to cause harmful side effects after targeting. By considering the
      combinatorial complexity of pathways from the outset, we can develop modeling
      tools that are better suited to analyzing large pathways, enabling us to identify
      new causal relationships. This could lead to new drug target strategies that
      beneficially disrupt host-pathogen interactions, minimizing the number of side
      effects. We introduce logic theory as part of a pathway modeling approach that
      can provide a new framework for understanding pathways and refine 'host-based'
      drug target identification strategies.

PMID- 20143943
TI  - Metagenomics for the discovery of novel human viruses.
AB  - Modern laboratory techniques for the detection of novel human viruses are greatly
      needed as physicians and epidemiologists increasingly deal with infectious
      diseases caused by new or previously unrecognized pathogens. There are many
      clinical syndromes in which viruses are suspected to play a role, but for which
      traditional microbiology techniques routinely fail in uncovering the etiologic
      agent. In addition, new viruses continue to challenge the human population owing
      to the encroachment of human settlements into animal and livestock habitats,
      globalization, climate change, growing numbers of immunocompromised people and
      bioterrorism. Metagenomics-based tools, such as microarrays and high-throughput
      sequencing are ideal for responding to these challenges. Pan-viral microarrays,
      containing representative sequences from all known viruses, have been used to
      detect novel and distantly-related variants of known viruses. Sequencing-based
      methods have also been successfully employed to detect novel viruses and have the
      potential to detect the full spectrum of viruses, including those present in low
      numbers.

PMID- 20143944
TI  - Target amplification for broad spectrum microbial diagnostics and detection.
AB  - Microarrays are massively parallel detection platforms that were first used
      extensively for gene expression studies, but have also been successfully applied
      to microbial detection in a number of diverse fields requiring broad-range
      microbial identification. This technology has enabled researchers to gain an
      insight into the microbial diversity of environmental samples, facilitated
      discovery of a number of new pathogens and enabled studies of multipathogen
      infections. In contrast to gene expression studies, the concentrations of targets
      in analyzed samples for microbial detection are usually much lower, and require
      the use of nucleic acid amplification techniques. The rapid advancement of
      manufacturing technologies has increased the content of the microarrays; thus,
      the required amplification is a challenging problem. The constant parallel
      improvements in both microarray and sample amplification techniques in the near
      future may lead to a radical progression in medical diagnostics and systems for
      efficient detection of microorganisms in the environment.

PMID- 20143945
TI  - Host-microbe interaction systems biology: lifecycle transcriptomics and
      comparative genomics.
AB  - The use of microarray and comparative genomic technologies for the analysis of
      host-pathogen interactions has led to a greater understanding of the biological
      systems involved in infectious disease processes. Transcriptome analysis of
      intracellular pathogens at single or multiple time points during infection offers
      insight into the pathogen intracellular lifecycle. Host-pathogen transcriptome
      analysis in vivo, over time, enables characterization of both the pathogen and
      the host during the dynamic, multicellular host response. Comparative genomics
      using hybridization microarray-based comparative whole-genome resequencing or de
      novo whole-genome sequencing can identify the genetic factors responsible for
      pathogen evolutionary divergence, emergence, reemergence or the genetic basis for
      different pathogenic phenotypes. Together, microarray and comparative genomic
      technologies will continue to advance our understanding of pathogen evolution and
      assist in combating human infectious disease.

PMID- 20143948
TI  - Proteomics as a probe of microbial pathogenesis and its molecular boundaries.
AB  - Proteomic technology offers an unprecedented systematic approach to investigate
      the protein complement of any organism. The field of microbial pathogenesis has
      greatly benefited from other systems approaches, and the application of
      proteomics to the study of infectious agents is beginning to emerge. Such
      applications include unambiguously identifying complete virulence factor
      inventories, studying the response of both host and pathogen to the infection
      process and elucidating mechanistic actions of virulence factors as they
      interface with host cells. This review will highlight examples where proteomic
      studies have contributed to our understanding of pathogenesis in these areas,
      with an emphasis on pathogens that employ type III and type IV secretion systems.
      In addition, we will discuss areas where proteomics may help shape further
      investigation and discovery in this field.

PMID- 20143947
TI  - Defining the humoral immune response to infectious agents using high-density
      protein microarrays.
AB  - A major component of the adaptive immune response to infection is the generation
      of protective and long-lasting humoral immunity. Traditional approaches to
      understanding the host's humoral immune response are unable to provide an
      integrated understanding of the antibody repertoire generated in response to
      infection. By studying multiple antigenic responses in parallel, we can learn
      more about the breadth and dynamics of the antibody response to infection.
      Measurement of antibody production following vaccination is also a gauge for
      efficacy, as generation of antibodies can protect from future infections and
      limit disease. Protein microarrays are well suited to identify, quantify and
      compare individual antigenic responses following exposure to infectious agents.
      This technology can be applied to the development of improved serodiagnostic
      tests, discovery of subunit vaccine antigen candidates, epidemiologic research
      and vaccine development, as well as providing novel insights into infectious
      disease and the immune system. In this review, we will discuss the use of protein
      microarrays as a powerful tool to define the humoral immune response to bacteria
      and viruses.

PMID- 20143946
TI  - Uncovering the interplay between CD8, CD4 and antibody responses to complex
      pathogens.
AB  - Vaccinia virus (VACV) was used as the vaccine strain to eradicate smallpox. VACV
      is still administered to healthcare workers or researchers who are at risk of
      contracting the virus, and to military personnel. Thus, VACV represents a weapon
      against outbreaks, both natural (e.g., monkeypox) or man-made (bioterror). This
      virus is also used as a vector for experimental vaccine development
      (cancer/infectious disease). As a prototypic poxvirus, VACV is a model system for
      studying host-pathogen interactions. Until recently, little was known about the
      targets of host immune responses, which was likely owing to VACVs large genome
      (>200 open reading frames). However, the last few years have witnessed an
      explosion of data, and VACV has quickly become a useful model to study adaptive
      immune responses. This review summarizes and highlights key findings based on
      identification of VACV antigens targeted by the immune system (CD4, CD8 and
      antibodies) and the complex interplay between responses.

PMID- 20143949
TI  - Never take candy from a stranger: the role of the bacterial glycome in host
      pathogen interactions.
AB  - With the comprehensive study and complete sequencing of the Haemophilus
      influenzae genome in 1995 came the term 'genomics' and the beginning of the
      'omics' era. Since this time, several analogous fields, such as transcriptomics
      and proteomics, have emerged. While growth and advancement in these fields have
      increased understanding of microbial virulence, the study of bacterial glycomes
      is still in its infancy and little is known concerning their role in host
      pathogen interactions. Bacterial glycomics is challenging owing to the diversity
      of glyco-conjugate molecules, vast array of unusual sugars and limited number of
      analytical approaches available. However, recent advances in glycomics
      technologies offer the potential for exploration and characterization of both the
      structures and functions of components of bacterial glycomes in a systematic
      manner. Such characterization is a prerequisite for discerning the role of
      bacterial glycans in the interaction between host defences and bacterial
      virulence factors.

PMID- 20143950
TI  - Global approaches to study protein-protein interactions among viruses and hosts.
AB  - While high-throughput protein-protein interaction screens were first published
      approximately 10 years ago, systematic attempts to map interactions among viruses
      and hosts started only a few years ago. HIV-human interactions dominate host
      pathogen interaction databases (with approximately 2000 interactions) despite the
      fact that probably none of these interactions have been identified in systematic
      interaction screens. Recently, combinations of protein interaction data with RNAi
      and other functional genomics data allowed researchers to model more complex
      interaction networks. The rapid progress in this area promises a flood of new
      data in the near future, with clinical applications as soon as structural and
      functional genomics catches up with next-generation sequencing of human variation
      and structure-based drug design.

PMID- 20143951
TI  - The use of RNAi-based screens to identify host proteins involved in viral
      replication.
AB  - The recent development of RNAi-based techniques for protein knockdown in
      mammalian cells has allowed for unprecedented flexibility in the study of protein
      function. Currently, large siRNA libraries are available that allow the knockdown
      of all proteins known to be encoded by the human genome. These libraries have
      been used to identify the host proteins required for the replication of several
      clinically important viruses, including HIV, flaviviruses and influenza. This
      review summarizes the methods used in RNAi-based screening for host factors
      involved in virus replication, and discusses published examples of such screens.

PMID- 20143952
TI  - Integration of 'omics' data: does it lead to new insights into host-microbe
      interactions?
AB  - The interaction between both beneficial and pathogenic microbes and their host
      has been the subject of many studies. Although the field of systems biology is
      rapidly evolving, the use of a systems biology approach by means of high
      throughput techniques to study host-microbe interactions is just beginning to be
      explored. In this review, we discuss some of the most recently developed high
      throughput 'omics' techniques and their use in the context of host-microbe
      interaction. Moreover, we highlight studies combining several techniques that are
      pioneering the integration of 'omics' data related to host-microbe interactions.
      Finally, we list the major challenges ahead for successful systems biology
      research on host-microbe interactions.

PMID- 20143955
TI  - 2,4-Dinitrophenol blocks neurodegeneration and preserves sciatic nerve function
      after trauma.
AB  - Preventing the harm caused by nerve degeneration is a major challenge in
      neurodegenerative diseases and in various forms of trauma to the nervous system.
      The aim of the current work was to investigate the effects of systemic
      administration of 2,4-dinitrophenol (DNP), a compound with newly recognized
      neuroprotective properties, on sciatic-nerve degeneration following a crush
      injury. Sciatic-nerve injury was induced by unilateral application of an aneurysm
      clip. Four groups of mice were used: uninjured, injured treated with vehicle
      (PBS), injured treated with two intraperitoneal doses of DNP (0.06 mg DNP/kg
      every 24 h), and injured treated with four doses of DNP (every 12 h). Animals
      were sacrificed 48 h post injury and both injured and uninjured (contralateral)
      sciatic nerves were processed for light and electron microscopy. Morphometric,
      ultrastructural, and immunohistochemical analysis of injured nerves established
      that DNP prevented axonal degeneration, blocked cytoskeletal disintegration, and
      preserved the immunoreactivity of amyloid precursor protein (APP) and Neuregulin
      1 (Nrg1), proteins implicated in neuronal survival and myelination. Functional
      tests revealed preservation of limb function following injury in DNP-treated
      animals. Results indicate that DNP prevents nerve degeneration and suggest that
      it may be a useful small-molecule adjuvant in the development of novel
      therapeutic approaches in nerve injury.

PMID- 20143954
TI  - Subfractionation of differentiating human embryonic stem cell populations allows
      the isolation of a mesodermal population enriched for intermediate mesoderm and
      putative renal progenitors.
AB  - Human embryonic stem (ES) cells are pluripotent and are believed to be able to
      generate all cell types in the body. As such, they have potential applications in
      regenerative therapy for kidney disease. However, before this can be achieved, a
      protocol to differentiate human ES cells to mesodermal renal progenitor lineages
      is required. Reduction of serum concentration and feeder layer density reduction
      cultures were used to differentiate human ES cells for 14 days. Differentiated ES
      cells were then fractionated by flow cytometry based on expression of the markers
      CD24, podocalyxin, and GCTM2 to isolate putative renal cells. These cells up
      regulated the expression of the renal transcription factors PAX2, LHX1, and WT1
      when compared with unfractionated human ES cells. Immunohistochemical assays
      confirmed that a subset of cells within this fraction co-expressed nuclear WT1
      and PAX2 proteins. Transcriptome profiling also showed that the most
      differentially up-regulated genes in this fraction preferentially associated with
      kidney development in comparison with any other lineage. When compared with a
      transcriptome profile database of urogenital development (GUDMAP), the top 200
      differentially up-regulated genes in this fraction strongly clustered into a
      group of genes associated with the metanephric mesenchyme at E11.5 and the
      corticonephrogenic interstitium at E15.5 of murine kidney development. Hence,
      this approach confirms an ability to direct human ES cells toward a renal
      progenitor state.

PMID- 20143956
TI  - Limited immune-modulating activity of porcine mesenchymal stromal cells abolishes
      their protective efficacy in acute kidney injury.
AB  - We demonstrated previously that administration of mesenchymal stromal cells
      (MSCs) after renal ischemia/reperfusion injury (IRI) in rats protected renal
      function and hastened repair through complex paracrine mechanisms. Here we
      investigated kidney-protective actions of MSCs in a porcine IRI model that may
      have relevance to human acute kidney injury (AKI). Groups of female pigs with
      bilateral IRI were infused with autologous or male allogeneic MSCs. No acute or
      late complications were observed, but unexpectedly, MSC therapy also had no
      beneficial effects on kidney function and histology. In vitro, we demonstrated
      substantial functional and phenotypic overlaps between rodent, human, and porcine
      MSCs, all of which exhibited trilineage differentiation, characteristic antigen
      profiles, and secretion of renoprotective vascular endothelial growth factor
      (VEGF)-A and insulin-like growth factor-1 (IGF-1). However, in striking contrast
      to human MSCs, porcine MSCs failed to inhibit the mixed lymphocyte reaction (MLR)
      and induced robust production of proinflammatory interleukin-6 (IL-6). In
      summary, in contrast to rodent models, treatment of porcine IRI with MSCs was not
      kidney-protective. This, we conclude, is due to the fact that porcine MSCs exert
      inadequate immune-modulating effects, further demonstrating that successful
      therapy of IRI with MSCs critically depends on their anti-inflammatory actions.
      As a consequence, treatment of AKI with MSCs is not informative regarding the
      investigation of the underlying mechanisms in this large animal model. We expect,
      however, that the treatment of human IRI of the kidney with immune-modulating
      MSCs will be as effective as in rodent models.

PMID- 20143957
TI  - Clinical factors that enhance morbidity and mortality in intrauterine growth
      restricted foetuses delivered between 23 and 30 weeks of gestation.
AB  - OBJECTIVE: To find clinical factors that are associated with poor outcome (death
      and brain damage) in premature intrauterine growth restricted (IUGR) infants.
      METHODS: A retrospective study was performed to compare the incidence of poor
      outcome between 45 IUGR and 203 appropriate-for-gestational-age (AGA) infants
      born before 30 weeks of gestation. Foetal tests included foetal heart rate
      monitoring, Doppler flow, amniotic fluid, and head circumference. Growth for
      gestational age was categorised as 10th through 3rd, third through first, and
      below first percentiles. RESULTS: In infants below 25 weeks of gestation, the
      incidence of poor outcome was not different between IUGR and AGA. In infants
      between 25 and 30 weeks of gestation, the incidence of poor outcome was
      significantly increased in IUGR compared with AGA (12/40, 30% versus 11/136,
      8.1%, p<0.01). Univariate analysis showed that abnormality in foetal heart rate
      monitoring [odds ratio (OR) 8.3, 95% confidence interval (CI) 1.58-43.6], head
      circumference (OR 7.0, 95%CI 1.42-34.4), and Doppler flow (OR 10.9, 95%CI 1.83
      64.6) was significantly associated with poor outcome in IUGR infants. However, no
      foetal tests were significantly associated with poor outcome after adjusting for
      the 3-grade birthweight percentiles. CONCLUSIONS: Immaturity outweighs clinical
      problem associated with IUGR in infants below 25 weeks of gestation. Between 25
      and 30 weeks of gestation, there was a growth threshold below third percentile
      where foetal tests were not significant predictors of poor outcome, but that was
      primarily determined by birthweight.

PMID- 20143958
TI  - Recognition of Japanese finger spelling gestures using neural networks.
AB  - Effective communication with the hearing and speech impaired often requires at
      least a basic working knowledge of sign language gestures, without which a memo
      pad and pen, or a mobile phone's notepad is indispensable. The aim of this study
      was to build a neural network that could be used to recognize static finger-hand
      gestures of the yubimoji, the Japanese sign language syllabary. To build the
      network, signal inputs from a data glove interface were taken for each of the
      static yubimoji gestures. The network was trained and tested 10 times using a
      multilayer perceptron model. Overall, only 18 of the 41 static gestures were
      successfully recognized. One of the reasons was attributed to the inability of
      the data glove to measure gesture directions particularly for yubimoji gestures
      with similar finger configurations. Future work will focus on these problems as
      well as the inclusion of dynamic yubimoji gestures.

PMID- 20143959
TI  - Attitude and opinion of neurosurgeons concerning protective bicycle-helmet use.
AB  - Wearing protective helmets decreases the risk of incurring traumatic brain injury
      (TBI) in bicycle accidents. In 2007, the German Neurosurgical Society advocated
      compulsory use of bicycle helmets. Although neurosurgeons are the specialists who
      primarily treat patients with TBI in Europe, the distribution of helmet users
      among neurosurgeons (NS), as well as factors that influence the decision to wear
      helmets and whether professional knowledge or experience in TBI influences the
      use or attitude concerning bicycle helmets, remains unclear. A total of 55
      neurosurgical departments in Germany, Austria, and Switzerland were contacted and
      asked to answer anonymous questionnaires concerning helmet use and TBI
      experience. To compare the neurosurgical attitude with that of a "non
      neurosurgical, non-TBI-educated" control group, people of the general public
      (PUB) were interviewed. A total of 465 NS and 546 PUB returned questionnaires,
      with 49.7% of the NS and 44.5% of PUB indicated that they wear helmets while
      bicycling. Trauma experience did effect the personal decision of whether to wear
      bicycle helmets. Support of compulsory use was influenced by TBI experience.
      Furthermore, the incidence of helmet use in children was correlated to actual
      helmet use and disposition of their parents to make helmet use compulsory. NS and
      PUB behaved in similar ways. Only half wear protective helmets, while the others
      show cognitive dissonant behavior. With respect to compulsory helmet use, NS are
      also split in half. Experience with TBI and trauma education has effects.
      However, education alone does not suffice in promoting the use of bicycle
      helmets.

PMID- 20143960
TI  - Measurement of migration of soft tissue by modified Roentgen
      stereophotogrammetric analysis (RSA): validation of a new technique to monitor
      rotator cuff tears.
AB  - The purpose of this study was to develop a technique to use Roentgen
      stereophotogrammetric analysis (RSA) to measure migration of soft-tissue
      structures after rotator cuff repair. RSA stereo films were obtained; images were
      analysed using a semi-automatic software program allowing 3D viewing of results.
      RSA imaging experiments were performed to validate the technique, using a glass
      phantom with implanted RSA beads and an animal model with steel sutures as RSA
      markers which were moved known distances. Repeated measurements allowed
      assessment of inter- and intra-observer variability at a maximum of 1.06 mm. RSA
      analysis of the phantom showed a variation up to 0.22 mm for static and 0.28 mm
      for dynamic studies. The ovine tissue specimen demonstrated that using steel
      sutures as RSA markers in soft tissue is feasible, although less accurate than
      when measuring bone motion. This novel application of RSA to measure soft tissue
      migration is practicable and can be extended to in vivo studies.

PMID- 20143961
TI  - Clinical efficacy of Japanese traditional herbal medicine (Kampo) in patients
      with late-onset hypogonadism.
AB  - INTRODUCTION: In addition to hormone replacement therapy, non-hormonal therapy,
      particularly Japanese traditional herbal medicine (Kampo), has been used to
      alleviate the various symptoms of female menopause. The efficacy and safety of
      Japanese traditional herbal medicine for male late-onset hypogonadism (LOH) are
      investigated. METHODS: One hundred fifty-one patients with LOH were treated via
      the administration of Japanese traditional herbal medicine. The most appropriate
      Japanese traditional herbal medicine was administered to patients according to
      their pathogenic alteration. After 4 weeks, the clinical efficacy was evaluated
      based on improvement of LOH symptoms and the score of the simplified menopausal
      index (SMI). Additionally, predictive factors of efficacy of Japanese traditional
      herbal medicine were analyzed. RESULTS: Among 151 patients with LOH, 63 (41.8%)
      achieved both relief from LOH symptoms and normalized SMI score (Excellent
      response group), whereas 44 (29.1%) achieved either relief from LOH symptoms or
      normalized SMI score (Fair). However, 44 (29.1%) patients displayed neither
      relief from LOH symptoms nor normalized SMI score (Poor). Adverse reactions were
      observed only in four (2.6%) patients. Patients displaying excess conditions and
      mild LOH symptoms appeared to be superior candidates for Japanese traditional
      herbal medicine. CONCLUSION: Japanese traditional herbal medicine is an effective
      and safe treatment for LOH.

PMID- 20143962
TI  - Swine flu and pregnancy.
AB  - Novel influenza A (H1N1) (H1N1 2009 influenza virus) or 'swine flu' has been
      identified as the cause of a widespread outbreak of respiratory infection
      worldwide. Based on experience from previous influenza pandemics, pregnant women
      are thought to be at a higher risk of contracting swine flu and developing
      complications. This review summarises the contemporaneous literature and advice
      on the management of swine flu in pregnancy in the UK, including the recent joint
      Department of Health and Royal College of Obstetricians and Gynaecologists'
      guidelines (October 2009).

PMID- 20143963
TI  - Maternal obesity: effects on pregnancy and the role of pre-conception
      counselling.
AB  - Obesity is an important public health issue not only in the general population,
      but also among pregnant women. Maternal obesity is associated with potential
      risks and complications for both the mother and the fetus. In this review, an
      update on the reproductive risks of maternal obesity and the role of pre
      conception counselling are presented.

PMID- 20143964
TI  - Is there an ideal interpregnancy interval after a live birth, miscarriage or
      other adverse pregnancy outcomes?
AB  - Advice given to women regarding optimum interpregnancy interval (IPI) following
      spontaneous miscarriage remains controversial. There is robust evidence from many
      studies including a meta-analysis that after full term or pre-term delivery, IPIs
      of <18 months and >5 years are associated with increased risk of poor perinatal
      and maternal outcome. However, there is paucity of good studies to infer the
      effect of IPI after a spontaneous miscarriage, which is a relatively common
      event. The results have been variable and inconsistent but a recent good quality
      study (DaVanzo et al. 2007 ) showed similar pregnancy outcome with IPIs of <6, 6
      14, 15-26 and 27-50 months following spontaneous miscarriage. Hence, it seems
      reasonable to attempt conception soon after an uncomplicated miscarriage in
      otherwise healthy women depending on their desire. More good quality, preferably
      prospective studies regarding effect IPI after miscarriage are required for
      better evidence-based advice.

PMID- 20143965
TI  - Tibial nerve stimulation for overactive bladder syndrome unresponsive to medical
      therapy.
AB  - Overactive bladder syndrome is defined as a symptom syndrome which includes
      urinary urgency, with or without urge incontinence, usually accompanied by
      frequency (>8 micturitions/24 h) and nocturia. Conservative treatment usually
      comprises behavioural techniques, bladder retraining, pelvic floor re-education
      and pharmacotherapy but up to 30% of patients will remain refractory to
      treatment. Although second-line treatment options such as sacral nerve
      stimulation and intravesical botulinum A injections are valuable additions to the
      therapeutic arsenal, they are relatively invasive and can have serious side
      effects. Inhibition of detrusor activity by peripheral neuromodulation of the
      posterior tibial nerve was first described in 1983, with recent authors further
      confirming a 60-80% positive response rate. This review was undertaken to examine
      published literature on percutaneous tibial nerve stimulation and to discuss
      outcome measures, maintenance therapy and prognostic factors of this technique.

PMID- 20143966
TI  - Meeting advanced learning needs of senior postgraduate trainees through practice
      based reflective medical education: evaluation of a formal structured training
      programme in obstetrics and gynaecology.
AB  - Postgraduate training programmes have gradually been focusing on a learner
      centred approach. We developed a 2-year rolling postgraduate educational
      programme in obstetrics and gynaecology to equip trainees with the knowledge,
      skills and attitudes necessary to promote self-directed learning. Its aim was to
      achieve this through critical analysis, application of knowledge and the
      attainment of skills relating to presentation, facilitation, feedback and
      assessment. Its evaluation using a trainees' feedback questionnaire (n = 21)
      showed that content of the pre-course work was scored favourably by 20 trainees,
      however one-third of trainees raised concerns about effectiveness and feasibility
      of the work. Lectures were preferred as the method of teaching by 17 compared
      with small group activity preferred by 14 trainees. The median scores for all
      items evaluated were above the threshold for concern. Our evaluation concluded
      that postgraduate teaching programmes based on principles of adult learning and
      reflective practice promote self-directed learning of professionally relevant
      objectives. Continuous evaluation helps to improve them further.

PMID- 20143967
TI  - Health information on the internet.
AB  - We did a prevalence survey among patients attending Obstetrics and Gynaecology
      clinics on internet-based health information accessed by our patients. Nearly 60%
      of patients had accessed web-based information before attending our specialist
      clinics. But only 4% were aware of the recommended website from which to access
      information. The patients felt the information obtained through common search
      engines like Yahoo and Google were unclear and confusing. With increasing access
      to internet-based health information, the medical community needs to address the
      problems of web-based health information and direct the patients to evaluated and
      approved websites.

PMID- 20143968
TI  - Butyrylcholinesterase activity in women with diabetes mellitus in pregnancy:
      correlation with antioxidant activity.
AB  - A total of: 25 women with gestational diabetes, 25 with type 2 diabetes, 21 with
      healthy pregnancies and 15 non-pregnant healthy controls were investigated to
      evaluate the relationship between butyrylcholinesterase activity and antioxidant
      status in the serum and placenta of diabetic pregnant women. Levels of
      antioxidant activities were estimated by Randox Kits and malondialdehyde and
      butyrylcholinesterase by colorimetric methods. Butyrylcholinesterase activity was
      elevated in the serum and placenta in normal pregnancy vs diabetic cohorts (p <
      0.01) and there was a higher activity level in gestational and type 2 diabetes on
      insulin (p < 0.05) compared with diet controlled. There was higher
      malondialdehyde and lower antioxidant activity in diet vs insulin controlled
      diabetes (p < 0.01). Serum and placental butyrylcholinesterase activity showed a
      strong inverse correlation with malondialdehyde (r = -0.876, p < 0.001) and (r =
      0.542, p < 0.01), but strong positive correlation with total antioxidant activity
      in serum (r = 0.764, p < 0.001) and placenta (r = 0.642, p < 0.01).
      Butyrylcholinesterase may therefore, be involved in reducing oxidative stress in
      diabetic pregnancy.

PMID- 20143969
TI  - Improved metabolic control and hepatic oxidative biomarkers with the
      periconception use of Helichrysum plicatum ssp. plicatum.
AB  - Our aim was to investigate the hypoglycaemic and antioxidant effects of the
      Helichrysum plicatum ssp. plicatum (HPsP) plant extract in the streptozotocin
      induced type 1 diabetes rat model during pregnancy. Five groups (n = 8, each)
      were formed: (1) diabetic non-mated control, (2) non-diabetic mated control, (3)
      diabetic mated control, (4) diabetic non-mated treatment and (5) diabetic mated
      treatment. The HPsP extract was administered orally for 15 days (250 mg/kg body
      weight), beginning 3 days before mating. The extract led to decreased blood
      glucose, increased serum insulin, and decreased serum triglycerides in pregnant
      and non-pregnant diabetic animals. Liver thiobarbituric acid reactive substances
      (TBARS) and reduced glutathione (GSH) measurements in extract-treated diabetics
      were similar to non-diabetic pregnant controls, indicating probable reversal of
      increased lipid peroxidation in the liver. The mean pup number tended to increase
      (p = 0.06) with extract administration. In conclusion, the beneficial effects we
      encountered with the periconception use of the studied herbal extract warrant
      further investigation.

PMID- 20143970
TI  - Maternal risk factors and anaemia in pregnancy: a prospective retrospective
      cohort study.
AB  - Anaemia in pregnancy is still a concern during the reproductive period, as it is
      associated with increased maternal and perinatal mortality and morbidity. This
      study examined the maternal risk factors associated with increased prevalence of
      anaemia among antenatal and postnatal women. A prospective-retrospective cohort
      approach was carried out among 1,077 antenatal and 1,000 postnatal women. The
      haemoglobin was estimated using the cyanmethaemoglobin method. The maternal
      factors included were age, parity, education, socioeconomic status, spacing,
      history of bleeding, worm infestation, period of gestation, knowledge regarding
      anaemia in pregnancy, food selection ability and compliance to iron
      supplementation. Of the 1,077 antenatal women studied, 540 were anaemic. Among
      the 1,000 postnatal women, the prevalence was 537 (53.7%). The high prevalence
      was strongly associated with low socioeconomic status (OR 1.409 [1.048-1.899]; p
      < 0.023) which affected their knowledge and health seeking behaviour in both the
      groups. Hence it can be concluded that empowering women in terms of education and
      economic status is the key factor in combating anaemia in pregnancy to prevent
      the vicious cycle of associated problems.

PMID- 20143971
TI  - Maternal vitamin D status throughout and after pregnancy.
AB  - Prospective longitudinal study of vitamin D status and its risk factors in 75
      pregnant women from early pregnancy until 6 months postpartum, by serial
      measurement of serum 25 (OH) vitamin D levels. The serum levels at booking were
      not significantly different between nationalities (p = 0.06), parity (p = 0.2),
      education levels (p = 0.4), dress code (p > 0.5), consumption of vitamin D
      fortified milk (p = 0.2) or, fatty fish (p = 0.5), sun-exposed body surface area
      (p = 0.3), weekly time exposed to the sun (p = 0.08) or the sun exposure index (p
      = 0.2). Vitamin D status progressively worsened as the proportion with adequate
      serum levels fell from 31% at the antenatal visit, to 23% after birth and 17%, 6
      months later (p = 0.02). While 80% of mothers who were exclusively breast-feeding
      had low vitamin D levels 6 months after delivery, this occurred in only 67% of
      those partially breast-feeding (p = 0.6).

PMID- 20143972
TI  - Oral health among antenatal care attendees in Calabar, Nigeria.
AB  - The objective of this study is to determine the oral health habits, awareness,
      oral health education and treatment needs among pregnant women who attend the
      antenatal clinics at the University of Calabar Teaching Hospital, Calabar,
      Nigeria. A total of 252 women at different stages of pregnancy responded to an
      interviewer-administered structured questionnaire. Of those, 238 (94.4%) of the
      respondents used toothbrush and toothpaste for oral cleaning, while 12 (4.8%)
      used a combination of toothbrush/toothpaste and local chewing sticks. Two (0.8%)
      adhered to the use of chewing sticks only. A total of 34 (13.5%) respondents were
      aware of and used dental services while pregnant; 18 (52.9%) of those who
      presented with dental complaints during pregnancy had bleeding gums. Based on the
      level of awareness of the need to attend a dental clinic during pregnancy (26.2%)
      and the percentage of respondents willing to have a dental examination during
      pregnancy (83.3%), it is recommended that oral health education be incorporated
      into the antenatal counselling of pregnant women in Nigeria.

PMID- 20143973
TI  - Erythrocyte antioxidant enzymes and plasma antioxidant vitamins in Sudanese women
      with pre-eclampsia.
AB  - This case-control study was conducted in Khartoum hospital, Sudan to investigate
      the levels of antioxidant enzymes (glutathione peroxidase, catalase and
      superoxide dismutase) in erythrocytes and plasma antioxidant vitamins (retinol
      and alpha-tocopherol) in Sudanese women with pre-eclampsia (37), in comparison
      with well-matched pregnant controls women with normal pregnancy (38). Enzymes
      were measured using ELISA and vitamins were measured using HPLC. There were no
      significant differences in the levels of these three antioxidant enzymes in pre
      eclamptic women compared with the controls. Women with mild pre-eclampsia
      (diastolic blood pressure, DBP < 110) have slightly higher levels of erythrocyte
      glutathione peroxidase, and lower levels of catalase and superoxide dismutase
      compared with women with severe pre-eclampsia (DBP > or = 110). A significantly
      negative correlation was observed between the levels of glutathione peroxidase
      and DBP, r = -0.371, p = 0.02. There was no significant correlation between
      catalase (r = -0.033, p = 0.840) or superoxide dismutase levels (r = 0.067, p =
      0.6) and DBP. While retinol levels were not different, levels of alpha-tocopherol
      were significantly higher in women with pre-eclampsia than the control group, p =
      0.026. The plasma levels of both vitamins were not statistically significantly
      different when women with mild and severe pre-eclampsia were compared.

PMID- 20143974
TI  - Erythrocyte omega-3 and omega-6 fatty acids profile in Sudanese women with pre
      eclampsia.
AB  - A case-control study was conducted in Khartoum hospital, Sudan to compare omega-3
      and omega-6 fatty acids profile in three phospholipid fractions
      (phosphatidylethanolamine, phosphatidylcholine and sphingomyelin) using gas
      chromatography in erythrocytes from 65 pre-eclamptic women and well-matched 60
      healthy control pregnant women, both in the third trimester of pregnancy. While
      levels of arachidonic acid (omega-6 fatty acid) was significantly higher in women
      with pre-eclampsia in the sphingomyelin fraction only, the levels of
      eicosapentaenoic and docosahexaenoic acid (omega-3 fatty acid) in the three
      phospholipids fractions were significantly higher in women with pre-eclampsia
      than in the control group. Both omega-3 and omega-6 fatty acids profiles were not
      significantly different between patients with mild (diastolic blood pressure
      (DBP) <110 mmHg) and severe (DBP > or = 110 mmHg) pre-eclampsia.

PMID- 20143975
TI  - Caesarean delivery or vaginal birth: preference of Turkish pregnant women and
      influencing factors.
AB  - The aim of this study was to assess the preference of pregnant women for mode of
      delivery in an uncomplicated pregnancy and reasons of their choice, also to
      determine if maternal characteristics were predictors of maternal preference.
      Pregnant women applying to the antenatal clinic for a routine control visit were
      recruited. After verbal consents, a questionnaire was administered to 1,588
      pregnant women. Of the women questioned, 84.1% opted for vaginal delivery whereas
      only 15.9% opted for an elective caesarean delivery. The main reasons for vaginal
      delivery preference were; earlier healing and earlier hospital discharge, being a
      more physiological way of delivery and previous vaginal delivery history. The
      most common reasons for choosing caesarean delivery were; fear of vaginal
      delivery, tubal ligation demand and to avoid labour pain. Educational status,
      occupation and gestational age were not found to be influencing factors but age,
      parity and monthly income were found to be influencing factors for maternal
      preference.

PMID- 20143976
TI  - The quality of operative consenting against RCOG advice as standard.
AB  - Clinical Governance Advice published by the RCOG states that 'before seeking a
      women's consent ... you should ensure that she understands the nature of the
      condition for which treatment is being proposed, its prognosis, likely
      consequences and risks of receiving no treatment at all'. The importance of
      obtaining informed consent within obstetrics and gynaecology is highlighted by
      the litigious nature of our specialty, with CNST data, demonstrating that it
      makes up 21% of all claims and incur highest cost of any other specialty. We
      present an audit of the quality of operative consenting for 120 procedures over a
      3-month period for five procedures (diagnostic hysteroscopy and laparoscopy,
      total abdominal hysterectomy, vaginal repair/hysterectomy and lower segment
      caesarean section) for which we have RCOG advice (Numbers 1, 2, 4, 5, 7,
      respectively). The quality of consent was also assessed by grade of clinicians.
      The results identify significant deficiencies when various gynaecological and
      obstetric procedures are being consented for, and we have discussed various
      options recommended for improvement.

PMID- 20143977
TI  - Preoperative assessment and consent for surgery: a role for the gynaecology nurse
      practitioner.
AB  - Over the last decade, nurse-led services have been introduced as an alternative
      pathway of patient care, in part to undertake work performed by trainee medical
      staff before the reduction in working hours. In response to the loss of trainee
      hours resulting from implementation of the European Working Time Directive, we
      set up a new service with a highly experienced gynaecology nurse who underwent
      additional training in preoperative assessment and consenting. The service was
      founded on the nurse-practitioner's expertise, together with the use of an
      integrated care pathway and 12 preformatted consent sheets. We undertook a case
      note review of 100 consecutive patients. The review of the service showed a high
      level of compliance for performance of laboratory and radiological
      investigations, both in terms of completion and the avoidance of unnecessary
      tests. In addition, the nurse-practitioner was able to obtain written consent
      from almost 87% of women undergoing surgery using a range of just nine
      preformatted sheets. No serious medical issues were overlooked and no operations
      were cancelled on the day of surgery. The quality of documentation was exemplary
      and there were no complaints or clinical incidents related to the nurse
      practitioner in 4 years of service. The quality of patient care can be
      maintained, if not improved, by integrating nurse-led preoperative assessment
      into the departmental clinical pathway for women choosing elective surgery.

PMID- 20143978
TI  - Pattern of contraceptive use among women with sickle cell disease in Ibadan,
      South-west Nigeria.
AB  - A cross-sectional study was conducted at the University College Hospital, Ibadan,
      Nigeria between January and April 2009. The purpose of this study was to
      determine the pattern of contraceptive use among females of reproductive age,
      with sickle cell (SC) disease, attending various clinics at the University
      College Hospital, Ibadan, Nigeria. It is evident in this study that even although
      contraceptive awareness in this group of patients is high, the prevalence of
      contraceptive use is very low which is comparable with the general population.
      This is largely due to perceived fear of real and imagined side-effects
      associated with some contraceptive methods and also relative lack of access to
      commodity sources. It is therefore suggested that there is need for effective
      enlightenment and health education targeted at this vulnerable group of women to
      dissipate unreal fears about contraception. Also, the provision of a
      contraceptive-friendly environment, especially at various clinics attended by
      sickle cell disease patients, to facilitate their access to contraceptive
      commodities will go a long way to enhance their uptake of contraception while
      preventing unwanted pregnancies along with other benefits in this susceptible
      group of women. The need for child spacing as well as limiting family size among
      sickle cell disease patients cannot be over emphasised.

PMID- 20143979
TI  - Young women opting for tubal sterilisation in rural India: reasons and
      implications.
AB  - The proportion of the women using tubal sterilisation is increasing, while the
      age at sterilisation is dropping. This prospective cross-sectional study explores
      factors that influence the women in rural India to undergo tubal sterilisation at
      a young age. In this study, 109 married women seeking tubal sterilisation from a
      community health centre were interviewed. Information included baseline
      reproductive data, knowledge about different contraceptive methods, prior
      contraceptive use, and reasons for choosing tubal sterilisation and knowledge
      regarding its failure rate and complications. The majority (65.1%) of women were
      below 30 years of age, and 69.7% had > or = 3 children. Approximately one-third
      (37.6%) had > or = 1 induced abortions. Although 65% of all women were aware of
      one or more temporary contraceptive methods, 53.2% had never used these because
      of worries regarding complications. Three-quarters of the women lacked knowledge
      about failure rate and complications of tubal sterilisation, and only 2.8%
      thought about future regrets. In rural India, there is lack of information,
      and/or misinformation about temporary contraception, affecting contraceptive use
      by women. An unhurried counselling along with unbiased information about
      alternative contraceptives would help these women for appropriate resolution of
      their reproductive need.

PMID- 20143980
TI  - An 'epidemic' of ectopic pregnancy in West Hertfordshire, UK?
AB  - Our clinical impression is that the incidence of ectopic pregnancy in West
      Hertfordshire in the UK has been steadily rising to almost 'epidemic'
      proportions. On the basis of our clinical suspicion, a retrospective study was
      performed looking at the ectopic pregnancy rates in the region from 1993 to 2007.
      All histologically proven ectopic pregnancies were obtained using the hospital
      histology database and all deliveries (live births and stillbirths) were obtained
      using the Ciconia Maternity information System (CMiS). The numbers of legal
      terminations of pregnancy (NHS and non-NHS) as well as women of reproductive age
      were obtained using the databases from the Office for National Statistics and
      Department of Health. In terms of absolute numbers of histologically proven
      ectopic pregnancies, there were 38 cases in 1993, rising to a peak of 68 cases in
      1998 and 59 cases in 2007. This equates to 6.5/1,000 deliveries in 1993, 11/1,000
      deliveries in 1998 and 10.7/1,000 deliveries in 2007. Although there have been
      fluctuations in ectopic pregnancy rates over 15 years, this did not reach
      statistical significance. Therefore, contrary to our clinical suspicion, the
      incidence of ectopic pregnancy in West Hertfordshire has remained stable.

PMID- 20143981
TI  - Endometriosis-associated Lyme disease.
AB  - The aim of this study is to report three cases of patients with endometriosis and
      infertility, and associated with Lyme disease. The medical files of 405 women
      with endometriosis and 200 without endometriosis were studied retrospectively. We
      report 3 cases with endometriosis and Lyme disease. Of 405 patients with
      endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme
      disease. All cases presented with typical erythema migraines, fever and fatigue.
      The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two
      out of 3 women underwent IVF-ET procedures and one of them conceived in the first
      cycle without complication during pregnancy or after childbirth recorded. We
      concluded that women with endometriosis are more likely to have chronic fatigue
      syndrome, systemic lupus erythematous, Sjogren's syndrome, rheumatoid arthritis,
      multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A
      review of the literature confirms the uniqueness of the co-existence of Lyme
      disease in women with endometriosis in these cases.

PMID- 20143982
TI  - Adnexal masses: relative accuracy of sonography and frozen section in predicting
      final pathology.
AB  - In this retrospective study, we compared the accuracy of frozen section and
      sonographic diagnosis in predicting the final paraffin section diagnosis of
      ovarian lesions. We hoped thereby to determine if sonographic findings could
      obviate the need for frozen section in certain circumstances. The frozen section
      and sonographic diagnosis were compared with the final paraffin section diagnosis
      to determine whether the lesion was felt to be a benign or malignant tumour.
      Frozen section diagnosis agreed with final paraffin section diagnosis in 137
      (77.4%) cases of primary malignant tumours, 201 (90.1%) cases of metastatic
      disease and 328 (82%) benign cases. Sonographic results matched final pathology
      of 133 cases of primary malignancy (75.1%) and 192 cases of metastatic disease
      (86.1%) and 304 benign cases (76%). Our study indicates that preoperative
      sonography is accurate enough in differentiating adnexal masses to make the
      routine use of frozen sections unnecessary.

PMID- 20143983
TI  - Managing women with post-coital bleeding: a prospective observational non
      comparative study.
AB  - The management of post-coital bleeding (PCB) is inconsistent in the UK and there
      are no guidelines to ensure good practice. This prospective study was conducted
      to review the management and identify the diagnostic outcome of 137 women treated
      according to a locally devised protocol based on the best available evidence.
      Women underwent smear testing, taking triple swabs and colposcopy. The
      endometrium was investigated in postmenopausal women and in those aged >35 years
      with associated intermenstrual bleeding. Of those who had PCB for >4 weeks, only
      8/124 (6.5%) were referred urgently. Twenty eight (20.4%) women were found to
      have significant pathology; 14 (50%) were <35 years of age, 26 (92.8%) had PCB
      for >4 weeks, whereas seven (25 %) suffered severe episodes, suggesting that the
      duration, but not age or severity, is relevant. A large multi-centre study is
      needed to provide more information in order to optimise the management.

PMID- 20143984
TI  - Intramural pregnancy.

PMID- 20143985
TI  - Incomplete abortion at 13 weeks' gestation due to extreme pelvic deformity in a
      woman with severe osteogenesis imperfecta.

PMID- 20143986
TI  - Intrauterine death in multiple gestation.

PMID- 20143987
TI  - The use of the birthing pool after a diagnosis of stillbirth.

PMID- 20143988
TI  - Labour dystocia due to faecal impaction after colostomy for faecaloma.

PMID- 20143989
TI  - Successful conservative management of inversion of a fibroid uterus by
      hydrostatic balloon.

PMID- 20143990
TI  - Postpartum femoral neuropathy following spontaneous vaginal delivery.

PMID- 20143991
TI  - Acquired vulval smooth muscle hamartoma in a postmenopausal woman, with no
      visible lesion.

PMID- 20143992
TI  - Using the Mirena intrauterine system to treat severe primary dysmenorrhoea in an
      adolescent.

PMID- 20143993
TI  - Uterine fibroid in an adolescent: an unlikely diagnosis?

PMID- 20143994
TI  - Fibroids as a cause of intraperitoneal haemorrhage.

PMID- 20143995
TI  - Leiomyomatosis peritonealis disseminata: an unusual presentation.

PMID- 20143996
TI  - Spontaneous uterine perforation secondary to uterine leiomyosarcoma presenting as
      acute abdomen with haemoperitoneum.

PMID- 20143997
TI  - Incidental finding of huge ovarian borderline mucinous tumour during management
      of laparoscopic gastric banding port infection.

PMID- 20143998
TI  - Gallbladder perforation: an unusual indirect complication of pelvic organ
      prolapse surgery.

PMID- 20143999
TI  - Three ipsilateral ectopic pregnancies managed surgically.

PMID- 20144000
TI  - Re: Manikkavasagan G, Ramsay M. 2009. The rationale for the use of measles post
      exposure prophylaxis in pregnant women: a review. Journal of Obstetrics and
      Gynaecology 29(7):574-577.

PMID- 20144002
TI  - Statement of retraction.

PMID- 20144001
TI  - Re: Okafor UV, Ezegwui HU, Ekwazi K. 2009. Trends of different forms of
      anaesthesia for caesarean section in South-eastern Nigeria. Journal of Obstetrics
      and Gynaecology 29(5): 392-395.

PMID- 20144003
TI  - What contributes to quality of life in adult survivors of childhood traumatic
      brain injury?
AB  - Adult outcome from childhood brain injury is largely unknown, and health
      professionals have minimal evidence available to inform families about their
      child's long-term prognosis. This study aimed to investigate long-term outcomes
      in this group, focusing on quality of life (QOL) and the injury, developmental,
      and environmental factors that influence this domain, using a retrospective and
      cross-sectional design. The sample was ascertained via medical record audit at
      the Royal Children's Hospital, Melbourne, Australia, and included 130 adult
      survivors of child traumatic brain injury (TBI) (84 men). Participants were 18-42
      years at evaluation (mean = 23.2, SD = 3.3) and completed questionnaires
      regarding QOL and educational, employment, and psychological status. Analysis of
      variance, chi-square, and regression were employed to assess group differences
      and predictors of outcome. While most adult survivors of childhood TBI rated
      their QOL as intact, 17% of the sample reported poor QOL. Poor QOL was more
      likely with low levels of perceived independence, severe TBI, younger age at
      injury, failure to complete high school, and psychological problems. In
      conclusion, QOL in adult survivors of childhood TBI is better than expected and
      closely associated with both injury and noninjury factors, most consistently with
      the individual's perception of their level of independence.

PMID- 20144004
TI  - Measuring verbal and non-verbal communication in aphasia: reliability, validity,
      and sensitivity to change of the Scenario Test.
AB  - BACKGROUND: This study explores the psychometric qualities of the Scenario Test,
      a new test to assess daily-life communication in severe aphasia. The test is
      innovative in that it: (1) examines the effectiveness of verbal and non-verbal
      communication; and (2) assesses patients' communication in an interactive
      setting, with a supportive communication partner. AIMS: To determine the
      reliability, validity, and sensitivity to change of the Scenario Test and discuss
      its clinical value. METHODS & PROCEDURES: The Scenario Test was administered to
      122 persons with aphasia after stroke and to 25 non-aphasic controls. Analyses
      were performed for the entire group of persons with aphasia, as well as for a
      subgroup of persons unable to communicate verbally (n = 43). Reliability
      (internal consistency, test-retest reliability, inter-judge, and intra-judge
      reliability) and validity (internal validity, convergent validity, known-groups
      validity) and sensitivity to change were examined using standard psychometric
      methods. OUTCOMES & RESULTS: The Scenario Test showed high levels of reliability.
      Internal consistency (Cronbach's alpha = 0.96; item-rest correlations = 0.58
      0.82) and test-retest reliability (ICC = 0.98) were high. Agreement between
      judges in total scores was good, as indicated by the high inter- and intra-judge
      reliability (ICC = 0.86-1.00). Agreement in scores on the individual items was
      also good (square-weighted kappa values 0.61-0.92). The test demonstrated good
      levels of validity. A principal component analysis for categorical data
      identified two dimensions, interpreted as general communication and communicative
      creativity. Correlations with three other instruments measuring communication in
      aphasia, that is, Spontaneous Speech interview from the Aachen Aphasia Test
      (AAT), Amsterdam-Nijmegen Everyday Language Test (ANELT), and Communicative
      Effectiveness Index (CETI), were moderate to strong (0.50-0.85) suggesting good
      convergent validity. Group differences were observed between persons with aphasia
      and non-aphasic controls, as well as between persons with aphasia unable to use
      speech to convey information and those able to communicate verbally; this
      indicates good known-groups validity. The test was sensitive to changes in
      performance, measured over a period of 6 months. CONCLUSIONS & IMPLICATIONS: The
      data support the reliability and validity of the Scenario Test as an instrument
      for examining daily-life communication in aphasia. The test focuses on multimodal
      communication; its psychometric qualities enable future studies on the effect of
      Alternative and Augmentative Communication (AAC) training in aphasia.

PMID- 20144005
TI  - Investigating children's ability to reflect on stored phonological
      representations: the Silent Deletion of Phonemes Task.
AB  - BACKGROUND: The development of children's speech, language, and literacy skills
      is considered to build on a robust and intact speech-processing system, with
      normally functioning skills at all levels of input and output processing, as well
      as storage. There are a range of tasks available that assess input and output
      processing skills, however there are few tasks described in the literature that
      require a child to reflect on and analyse the internal structure of their own
      phonological representations. AIMS: This paper will describe the development of
      the Silent Deletion of Phonemes (SDOP) task. This task is designed to assess a
      child's ability to delete and manipulate sounds silently within their own stored
      representations while minimizing the impact of any output difficulties. METHODS &
      PROCEDURES: The SDOP task was presented to 69 typically developing mainstream
      Year 2 children (aged 7;2-8;1 years) as part of a battery of phonological
      processing skills and literacy measures. OUTCOMES & RESULTS: Scores for the
      population of typically developing Year 2 children were normally distributed and
      above a basal level but not approaching ceiling. Performance on the SDOP was
      significantly correlated with other measures of phonological processing but not a
      measure of non-verbal ability. It was most highly correlated with the measure of
      phonological awareness as expected, as both tasks measure awareness of the
      internal structure of words. However, the SDOP provided more information about
      the accuracy and specificity of a child's underlying phonological
      representations. The SDOP explained a significant amount of concurrent variance
      in both reading and spelling performance beyond the variance accounted for by the
      predictors that have been used by researchers to date. In combination, the SDOP
      and rapid-naming measure accounted for 58.8% of variance in performance on the
      reading measure and 54.4% of variance in spelling performance. CONCLUSIONS &
      IMPLICATIONS: The SDOP task appears to be a valid and reliable tool to assess the
      internal structure of a child's stored phonological representations. Profiling
      phonological representations allows clinicians to explore children's speech
      processing skills which may be particularly useful with children with complex
      literacy difficulties.

PMID- 20144006
TI  - Communication and Huntington's disease: qualitative interviews and focus groups
      with persons with Huntington's disease, family members, and carers.
AB  - BACKGROUND: As an effect of the cognitive, emotional and motor symptoms
      associated with Huntington's disease, communicative interaction is often
      dramatically changed. No study has previously included the subjective reports on
      this subject from individuals with Huntington's disease. AIMS: To explore the
      qualitative aspects of how communication is affected by Huntington's disease from
      a triangular perspective represented by individuals with Huntington's disease,
      family members and professional carers. METHODS & PROCEDURES: Eleven persons with
      Huntington's disease, seven family members and ten carers were interviewed in
      focus groups or individually, using a semi-structured interview guide. The
      interviews were transcribed verbatim and analysed using thematic content
      analysis, resulting in a number of free codes concerning communication. The codes
      describing related phenomena were merged into categories. Categories were
      analysed and reanalysed resulting in three major themes, common to the three
      groups of participants. OUTCOMES & RESULTS: The themes found were: Communication
      has changed; Factors that influence communication negatively; and Factors that
      influence communication positively. Subcategories differed between the three
      groups. All participants seemed to acknowledge the variability and lack of
      initiative in communication. The persons without Huntington's disease focused on
      the changes in terms of speech, language comprehension, the lack of depth in
      conversation and the need to make adjustments, while the persons with
      Huntington's disease focused on the effort and concentration demanded to
      communicate. They described the change they perceived in their communicative
      ability in terms of loss. All participants thought that an emotional load had a
      negative impact on communication. Furthermore, individuals with Huntington's
      disease stressed that other people's speed of communication had a negative
      impact, while family members and carers stressed that things such as personality
      changes in persons with Huntington's disease and lack of eye contact with them
      influenced communication negatively. All participants acknowledged the need for
      increased participation in social life in order to enhance communication.
      CONCLUSIONS & IMPLICATIONS: In brief, persons with Huntington's disease expressed
      a need for a richer social life and more (adjusting) conversation partners,
      family members expressed a need for more support and professional carers wanted
      more information about Huntington's disease. The triangular perspective utilized
      in the present study completed the picture of the communicative consequences of
      Huntington's disease. In particular, it became clear, that the insights of
      persons with Huntington's disease can and has to be included in communicative
      assessments and plans for intervention.

PMID- 20144007
TI  - Pragmatic language and the child with emotional/behavioural difficulties (EBD): a
      pilot study exploring the interaction between behaviour and communication
      disability.
AB  - INTRODUCTION: The relationship between mental health, behaviour and language
      development is widely recognized in the literature. Recent advances in assessment
      tools allows one to consider the role of pragmatic language skills in this co
      occurrence. AIMS: This pilot study aimed to investigate (1) the level of
      association between pragmatic language difficulties and emotional/behavioural
      difficulties; and (2) what explanations there might there be for any such
      association. The roles of language, word decoding, and non-verbal cognitive
      ability and also socio-demographic factors are considered. METHOD & PROCEDURES:
      Seventeen participants aged 7-11 years were identified from Educational
      Psychologist caseloads as having behaviour that is causing concern at school.
      Comparisons were made with 16 age- and sex-matched controls. Participants'
      language, literacy and non-verbal cognitive ability were assessed at school.
      Parents and teachers completed questionnaires investigating communication skills,
      behaviour and emotional wellbeing. OUTCOMES & RESULTS: No significant difference
      was found between the groups for non-verbal cognitive ability. However, children
      in the referred group were significantly more likely to have structural language,
      word decoding and pragmatic language difficulties and mothers with no further
      education beyond school. Taking a broad view of language skills to include
      structural language, pragmatic language and word decoding, 94% (n = 15) of
      referred children had significant difficulties with at least one of these three
      factors. The only factor not found on its own was structural language
      difficulties, indicating that on their own they are perhaps not associated with
      emotional/behavioural difficulties. CONCLUSIONS & IMPLICATIONS: The results of
      this pilot study have implications for how we view language and behaviour
      difficulties in primary schools. Future larger-scale research should consider the
      role of parenting factors, pragmatic language skills and literacy ability in the
      high co-existence rate of emotional/behavioural difficulties and
      language/communication needs.

PMID- 20144008
TI  - The use of facilitative vowel contexts in the treatment of post-alveolar
      fronting: a case study.
AB  - BACKGROUND: School-aged children with persisting speech sound disorders (SSDs)
      may show little improvement in speech accuracy following phonological or
      articulation therapy. AIMS: To determine the effects of establishing consonant
      production in facilitative vowel contexts for a 7-year-old boy (CD) with
      persisting post-alveolar fronting. CD had received phonological awareness therapy
      and traditional articulation therapy as part of a community caseload. However,
      his post-alveolar fronting showed resistance to therapy. METHODS & PROCEDURES: CD
      received individual therapy for nine 45-55-min sessions. A checklist of quality
      indicators for single-subject research was used to explore the likelihood that a
      community clinic could meet quality indicators. Fifteen test words in each of
      target, generalization and control sets were measured at five times pre-, during
      and post-therapy. A trend analysis was used to measure the statistical
      significance of the results and to demonstrate the efficacy of therapy. OUTCOMES
      & RESULTS: Therapy was successful. Gains on treatment and generalization test
      items were rapid and significantly higher than gains on control test items. Only
      three of 21 single-subject research quality indicators were not met in this
      research. CONCLUSIONS & IMPLICATIONS: Targeting facilitative vowel contexts was
      successful for this 7-year-old boy with persisting post-alveolar fronting which
      had been resistant to other therapy techniques. Speech and language therapists
      are encouraged to ensure that quality indicators for single-subject interventions
      are built into regular practice.

PMID- 20144009
TI  - An exploratory trial of the effectiveness of an enhanced consultative approach to
      delivering speech and language intervention in schools.
AB  - BACKGROUND: Increased demand for access to specialist services for providing
      support to children with speech, language and communication needs prompted a
      local service review of how best to allocate limited resources. This study arose
      as a consequence of a wish to evaluate the effectiveness of an enhanced
      consultative approach to delivering speech and language intervention in local
      schools. AIMS: The purpose was to evaluate an intensive speech and language
      intervention for children in mainstream schools delivered by specialist teaching
      assistants. METHODS & PROCEDURES: A within-subjects, quasi-experimental
      exploratory trial was conducted, with each child serving as his or her own
      control with respect to the primary outcome measure. Thirty-five children between
      the ages of 4;2 and 6;10 (years; months) received speech and/or language
      intervention for an average of four 1-hour sessions per week over 10 weeks. The
      primary outcome measure consisted of change between pre- and post-intervention
      scores on probe tasks of treated and untreated behaviours summed across the group
      of children, and maintenance probes of treated behaviours. Secondary outcome
      measures included standardized tests (Clinical Evaluation of Language
      Fundamentals - Preschool(UK) (CELF-P(UK)); Diagnostic Evaluation of Articulation
      and Phonology (DEAP)) and questionnaires completed by parents/carers and school
      staff before and after the intervention period. OUTCOME & RESULTS: The primary
      outcome measure showed improvement over the intervention period, with target
      behaviours showing a significantly larger increase than control behaviours. The
      gains made on the target behaviours as a result of intervention were sustained
      when reassessed 3-12 months later. These findings were replicated on a second set
      of targets and controls. Significant gains were also observed on CELF
      Preschool(UK) receptive and expressive language standard scores from pre- to post
      intervention. However, DEAP standard scores of speech ability did not increase
      over the intervention period, although improvements in raw scores were observed.
      Questionnaires completed before and after intervention showed some significant
      differences relating to how much the child's speech and language difficulties
      affected him/her at home and at school. CONCLUSIONS & IMPLICATIONS: This
      exploratory study demonstrates the benefit of an intensive therapy delivered by
      specialist teaching assistants for remediating speech and language difficulties
      experienced by young children in mainstream schools. The service delivery model
      was perceived by professionals as offering an inclusive and effective practice
      and provides empirical support for using both direct and indirect intervention in
      the school setting.

PMID- 20144010
TI  - Addition of contingency management to increase home practice in young children
      with a speech sound disorder.
AB  - BACKGROUND: Along with the severity of the disorder, the motivation of the
      children and their parents is an important element in explaining the extensive
      variance in therapeutic success. There is consensus that parental cooperation and
      homework are important for successful therapy. Systematic investigation into the
      effects of including homework in therapy is lacking, as are methodological
      approaches to increasing parental involvement. AIMS: The aim was to determine
      whether the efficiency of traditional articulation therapy for children with
      speech-sound disorders can be improved by adding a behavioural treatment approach
      (contingency management) to treatment in order to increase the time that patients
      spend doing homework. METHODS & PROCEDURES: A total of 91 children between the
      ages of four and six with articulation impairments participated in the study.
      They were divided into three groups: 32 children were treated with traditional
      articulation therapy (eight sessions of 45 minutes each), 33 children received a
      combination of contingency management and traditional therapy, and 26 children
      received no therapy at all. A picture-labelling test measuring the treated target
      sound at different levels was used before and after therapy to quantify therapy
      induced improvement. OUTCOMES & RESULTS: The results confirm the fact that the
      traditional articulation therapy approach is effective for children with
      articulation impairments. However, adding contingency management significantly
      increased the frequency of homework sessions and improved the efficiency of
      treatment by decreasing the variance in therapeutic success. CONCLUSIONS &
      IMPLICATIONS: Contingency management has a positive impact on therapeutic success
      and leads to an increase in the number of homework sessions.

PMID- 20144011
TI  - How to distinguish normal from disordered children with poor language or motor
      skills.
AB  - BACKGROUND & AIMS: We tested the Diagnostic and Statistical Manual of Mental
      Disorders (DSM) hypothesis that so-called specific developmental disorders are
      marked by a pattern of specific discrepant achievement, and an alternative
      hypothesis that children with these disorders show a pattern of relatively
      pervasive low achievement. METHODS & PROCEDURES: Children with a diagnosis of
      Mixed Receptive Expressive Language Disorder (RELD; n = 21) were compared with
      children with no previously suspected disorder but low standard language scores (
      < 80; n = 22) selected from a representative sample, and children with
      Developmental Coordination Disorder (DCD; n = 20) were compared with children
      with no previously suspected disorder but low standard motor skills scores (n =
      28) selected from a representative sample. OUTCOMES & RESULTS: Children with
      diagnosed disorders were more pervasive underachievers. The RELD group obtained
      lower scores on measures of verbal comprehension, emotion understanding, theory
      of mind, working memory and response inhibition; the DCD group obtained lower
      scores on measures of perceptual organization, verbal comprehension, receptive
      and expressive language, and visual inspection time. CONCLUSIONS & IMPLICATIONS:
      We conclude that relatively pervasive underachievement distinguishes disordered
      from normal low achievers.

PMID- 20144012
TI  - Suspension matrices for improved Schwann-cell survival after implantation into
      the injured rat spinal cord.
AB  - Trauma to the spinal cord produces endogenously irreversible tissue and
      functional loss, requiring the application of therapeutic approaches to achieve
      meaningful restoration. Cellular strategies, in particular Schwann-cell
      implantation, have shown promise in overcoming many of the obstacles facing
      successful repair of the injured spinal cord. Here, we show that the implantation
      of Schwann cells as cell suspensions with in-situ gelling laminin:collagen
      matrices after spinal-cord contusion significantly enhances long-term cell
      survival but not proliferation, as well as improves graft vascularization and the
      degree of axonal in-growth over the standard implantation vehicle, minimal media.
      The use of a matrix to suspend cells prior to implantation should be an important
      consideration for achieving improved survival and effectiveness of cellular
      therapies for future clinical application.

PMID- 20144013
TI  - Effects of hyperinsulinemia on lipolytic function of three-dimensional
      adipocyte/endothelial co-cultures.
AB  - The increased incidence of both type 2 diabetes mellitus and obesity has prompted
      the need to develop physiologically relevant adipose tissue models for controlled
      study of both normal and diseased adipose functions. Insulin resistance,
      characteristic of both type 2 diabetes mellitus and obesity, is often preceded by
      hyperinsulinemia. We propose here a three-dimensional (3D) co-culture adipose
      tissue model to study the effects of high insulin exposure, which enabled the
      study of physiological cell responses to hyperinsulinemic conditions. Two
      dimensional adipocyte studies were initially conducted to establish a baseline
      control in which insulin levels were established. Adipocytes and endothelial
      cells were subsequently co-cultured on 3D porous silk fibroin scaffolds in normal
      or high insulin concentrations, and their physiological responses were assessed
      with respect to lipogenesis and lipolysis. High insulin levels stimulated both an
      increase in triglyceride accumulation and a decrease in lipolysis levels compared
      to that of normal insulin conditions. In contrast, adipocyte monocultures did not
      exhibit any differences between insulin levels. The ability of this 3D system to
      elicit physiological responses to hyperinsulinemia in co-culture serves as a
      significant step forward in adipose tissue engineering. The development of
      physiologically relevant 3D in vitro adipose tissue models presents promise for
      the study of disease mechanisms as well as in assessing therapeutic treatments.

PMID- 20144015
TI  - Epidemiological profile of meningococcal disease in the United States.
AB  - Neisseria meningitidis is a leading cause of bacterial meningitis and other
      serious infections worldwide. The epidemiological profile of N. meningitidis is
      highly changeable, with great differences in disease incidence and serogroup
      distribution. Six serogroups (namely serogroups A, B, C, W-135, X, and Y) are
      responsible for most cases of meningococcal disease worldwide; the
      epidemiological profile of disease caused by each serogroup is unique. No vaccine
      is available for endemic disease caused by serogroup B strains. Two tetravalent
      (A/C/Y/W-135) meningococcal vaccines are licensed in the United States: a
      purified polysaccharide product and a polysaccharide-protein conjugate vaccine.
      The conjugate vaccine is recommended for all adolescents, although vaccine
      coverage remains low, and other groups at high risk of infection. A comprehensive
      program to prevent invasive meningococcal disease in the United States will
      require vaccination of infants; several conjugate vaccines for infants may become
      available in the near future. Broadly protective vaccines for endemic serogroup B
      disease are also needed.

PMID- 20144016
TI  - Prevention of meningococcal disease: current use of polysaccharide and conjugate
      vaccines.
AB  - Invasive meningococcal disease (IMD), although uncommon, is difficult to diagnose
      and can be rapidly fatal, even in healthy young persons. IMD is cyclic, and
      serogroups responsible for disease vary by age group, although the prevalence of
      the serogroups changes over time and by geographical location. Two quadrivalent
      vaccines are licensed in the United States to prevent IMD caused by serogroups A,
      C, Y, and W-135, and the US Centers for Disease Control and Prevention recommends
      routine vaccination with quadrivalent meningococcal conjugate vaccine of
      adolescents 11-18 years of age and vaccination of persons 2-55 years of age who
      are at elevated risk of IMD. Efforts to prevent IMD remain challenging, because
      there is neither an immunogenic vaccine for infants nor a vaccine to prevent
      serogroup B disease that is currently licensed. Obstacles to achieving optimal
      vaccine coverage among adolescents persist, and strategies are needed to address
      these shortcomings.

PMID- 20144018
TI  - Combined interventions may improve success when treating sudden cardiac arrest.
AB  - Recently, emphasis has been placed on the simultaneous implementation of
      resuscitation interventions currently recommended within the 2005 American Heart
      Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and
      emergency cardiac care (ECC). The rate of successful outcomes from out-of
      hospital cardiac arrest remains relatively low in most U.S. communities. Accurate
      measures of these rates are difficult to determine because of ineffective
      reporting mechanisms. In many cases of acute myocardial infarction, the initial
      presentation of symptoms is quickly followed by sudden death. Little information
      exists regarding the system-of-care components most likely to result in
      successful outcomes. Inconsistent application of these components may be
      responsible in part for the variability of survival rates among communities. We
      present a case of acute myocardial infarction followed by sudden cardiac arrest
      benefiting from the application of coordinated, community-based systems of care.

PMID- 20144019
TI  - A qualitative study to understand barriers to implementation of national
      guidelines for prehospital termination of unsuccessful resuscitation efforts.
AB  - BACKGROUND: The American Heart Association's (AHA's) Advanced Cardiac Life
      Support guidelines act as the national standards for termination of resuscitation
      (TOR) in cases of refractory out-of-hospital cardiac arrest. However, local
      emergency medical services (EMS) implementation of these guidelines has been
      nonuniform. OBJECTIVE: To identify the operational issues within local EMS
      systems that may serve as barriers or facilitators to full acceptance of national
      guidelines for prehospital TOR in appropriate circumstances. Methods. We
      conducted three focus groups at the January 2008 National Association of EMS
      Physicians (NAEMSP) annual meeting. Snowball sampling was used to recruit 19
      physicians, two EMS providers, one research director, one nurse, and one medical
      student attending the conference. Two reviewers analyzed the data in an iterative
      process to identify recurrent and unifying themes. RESULTS: We identified three
      distinct stakeholder groups whose current beliefs and practices may influence
      local implementation of TOR: EMS providers with variations in education and work
      culture; EMS medical directors with responsibility but little authority; and
      online medical control physicians who do not communicate effectively with the
      other groups. Our focus group participants suggested that national organizations,
      such as the AHA and the American College of Emergency Physicians, may serve a
      role in overcoming the overarching barriers of communication, standardized
      educational requirements, and coordination of local services. CONCLUSION: We have
      identified operational barriers that may impede implementation of TOR guidelines.
      Three influential stakeholder groups will need to work with national
      organizations to overcome these local barriers.

PMID- 20144017
TI  - Review of meningococcal group B vaccines.
AB  - No broadly effective vaccines are available for prevention of group B
      meningococcal disease, which accounts for >50% of all cases. The group B capsule
      is an autoantigen and is not a suitable vaccine target. Outer-membrane vesicle
      vaccines appear to be safe and effective, but serum bactericidal responses in
      infants are specific for a porin protein, PorA, which is antigenically variable.
      To broaden protection, outer-membrane vesicle vaccines have been prepared from >1
      strain, from mutants with >1 PorA, or from mutants with genetically detoxified
      endotoxin and overexpressed desirable antigens, such as factor H binding protein.
      Also, recombinant protein vaccines such as factor H binding protein, given alone
      or in combination with other antigens, are in late-stage clinical development and
      may be effective against the majority of group B strains. Thus, the prospects
      have never been better for developing vaccines for prevention of meningococcal
      disease, including that caused by group B strains.

PMID- 20144020
TI  - EMS and managed care: the Los Angeles experience.
AB  - BACKGROUND: Patients belonging to a managed care organization (MCO) who call 9-1
      1 are typically transported to their MCO facility only if it is also the closest
      emergency department (ED). As past medical records and close follow-up are
      unavailable at the non-MCO facility, unnecessary workups and/or admissions may
      result. OBJECTIVE: To examine the safety and feasibility of preferentially
      transporting MCO patients to the closest MCO ED rather than the closest ED.
      METHODS: This was a retrospective review over a 52-month period comparing all
      patients transported by ambulance to an MCO ED when that destination was not the
      closest ED (targeted group) with all other transported patients. If the MCO
      facility was not the closest ED, then the emergency medical services (EMS)
      provider would be reimbursed an additional fee beyond the routine ambulance
      charges. The primary outcome measure was the additional ambulance transport time.
      The secondary outcome measure was mortality within the first 24 hours. RESULTS:
      There were 15,938 patients transported under this program from July 2000 through
      December 2004 for whom outcome data were available. Of these, 10,532 (66%) were
      transported by advanced life support (ALS) ambulance. The mean (+/- standard
      deviation) transport time to the hospital for all targeted patients transported
      during the study interval was 10.4 minutes (+/-3.2 minutes) compared with 8.6
      minutes (+/-2.1 minutes) for all transported patients (p < 0.001). No patient
      required ventilatory support in the field. Twelve (0.1%) patients died during the
      subsequent hospital admission and, after a blinded chart review, none of the
      deaths were deemed to be preventable or likely to have resulted from additional
      transport time. CONCLUSION: Our study suggests that paramedic transport of MCO
      patients to the nearest MCO hospital in lieu of the nearest ED is safe and
      feasible. Given the potential benefits to patient care, this program should be
      evaluated in other EMS systems.

PMID- 20144021
TI  - Antegrade ureteral stenting during laparoscopic dismembered pyeloplasty:
      intraoperative findings and long-term outcome.
AB  - OBJECTIVE: The objective of this study was to compare the results of antegrade
      (AG) ureteral stenting with retrograde (RG) stenting during laparoscopic
      dismembered pyeloplasty. MATERIALS AND METHODS: Between October 2003 and April
      2007, a case series of 47 laparoscopic dismembered pyeloplasties were done by
      three surgeons of equal expertise in laparoscopic surgery, where the Double-J
      ureteral stent was placed by the RG method (RG stenting group) in 15 cases and by
      the AG method (AG stenting group) in 32 patients. Intraoperative findings and
      operative data were recorded. Clinical and radiological outcomes were evaluated
      during the follow-up visits at 3, 6, 12 months and then annually. RESULTS:
      Differences in patient's age and body mass index were not statistically
      significant. Laparoscopic pyeloplasty was successfully completed in 45 patients,
      with two cases of conversion to open (one in each group). A crossing vessel was
      identified in 42% of RG stenting group versus 45% of AG stenting group. A state
      of high ureteral insertion was identified in 16% of AG stenting group, a finding
      that was never seen in RG stenting group. Mean operative time was 271 +/- 21
      minutes for RG stenting group versus 199 +/- 34 minutes for AG stenting group, a
      difference that was statistically significant (p <or= 0.01). Differences in
      estimated blood loss, hemoglobin decline, time to oral feeding, duration of
      urethral catheter, and length of hospital stay were not significant.
      Postoperative complications were seen in two patients: postoperative hematuria
      belonging to RG stenting group was managed endoscopically and prolonged urine
      leakage belonging to AG stenting group ceased spontaneously by postoperative day
      8. Clinical and radiological improvement was evident in 97%, with a mean follow
      up of 30 +/- 17 months. CONCLUSIONS: AG ureteral stenting is technically feasible
      and provides better dissection, especially in patients with high ureteral
      insertion and secondary ureteropelvic junction obstruction, with good long-term
      outcome in both groups.

PMID- 20144022
TI  - Analysis of pitfalls encountered by residents in transurethral procedures in
      master-apprentice type of training.
AB  - BACKGROUND AND PURPOSE: Today's simulators are frequently limited in their
      possibilities to train all aspects of endourological procedures. It is therefore
      indicated to first make an inventory of training needs before (re)developing
      simulators. This study examined pitfalls encountered by residents in real-time
      transurethral procedures. MATERIALS AND METHODS: First, difficulties that
      residents encounter in transurethral procedures (transurethral resection of the
      bladder tumor [TURBT], transurethral resection of the prostate [TURP],
      ureterorenoscopy [URS]) were identified by asking urologists and residents to
      complete an open questionnaire. Based on their answers a list of pitfalls was
      designed and tested in 28 pilot observations. Then, two raters (interrater
      agreement 0.72, 0.70, and 0.75 for TURBT, TURP, and URS, respectively)
      categorized all observed procedure-related interactions between residents and
      supervisors in 80 procedures as (1) (type of ) pitfall or (2) no pitfall.
      RESULTS: Pitfalls most frequently encountered were as follows: (1)
      planning/anticipation on new situations (median 27.3%, 29.3%, and 31.8% of total
      pitfalls in TURBT, TURP, and URS, respectively); (2) handling of instruments
      (11.5%, 10.6%, and 20.0% for TURBT, TURP, and URS); (3) irrigation management for
      TURBT (7.7%), depth of resection for TURP (8.9%), and use of X-ray for URS
      (13.3%). CONCLUSION: Designers of endourological simulators should include
      possibilities to train planning/anticipation on new situations, handling of
      instruments in all transurethral procedures, and irrigation management in TURBT,
      depth of resection in TURP, and timing usage of X-ray in URS.

PMID- 20144023
TI  - Education on end-of-life care in the medical curriculum: students' opinions and
      knowledge.
AB  - OBJECTIVES: The aims of this study were to investigate: (1) opinions of medical
      students regarding quantity and content of education on end-of-life care in the
      curriculum, (2) medical students' knowledge of different aspects of the
      euthanasia act, and (3) factors associated with positive opinions about the
      quantity and content of education on end-of-life care in the curriculum. METHODS:
      A total of 204 medical students received a questionnaire; 176 completed it
      (response rate, 86%). RESULTS: Approximately half of the students (55%)
      considered the quantity of end-of-life care education in the curriculum moderate;
      35% rated it as good. Half of the students rated the content of end-of-life care
      education as moderate (50%); 47% rated it as good. Fourteen percent of the
      students gave correct answers to 6 or 7 of the 8 questions about the euthanasia
      act. Students who took the elective course "Terminal and Palliative Care,"
      students who had experience with a patient requesting euthanasia and physician
      assisted suicide in their personal lives, and students with more knowledge of the
      euthanasia act were more positive about the quantity of end-of-life care
      education. Students who completed fewer clerkships and totally agreed with the
      statement, "Everyone has the right to decide about their own life and death" were
      more positive about the content on end-of-life care education. CONCLUSIONS: The
      data of this study suggest that more attention can and should be paid to
      education on end-of-life care in the medical curriculum, so students are well
      prepared to provide adequate end-of-life care.

PMID- 20144024
TI  - Family support in pediatric palliative care: how are families impacted by their
      children's illnesses?
AB  - CONTEXT: Palliative care programs have the opportunity to intercede and provide
      supportive care to parents whose families have been impacted by their children's
      illnesses. By understanding how families are impacted, programs can refine their
      service provision and investigate unmet needs. OBJECTIVE: To determine how
      families are impacted and what factors are associated with greater impact.
      DESIGN: 2008 cross-sectional telephone survey. SETTING: Florida. PATIENTS: Eighty
      five parents whose children had life-limiting illnesses and were enrolled in
      Florida's publicly funded pediatric palliative care program. MAIN OUTCOME
      MEASURE: The Impact on Family (IOF) Scale. RESULTS: The majority of parents who
      responded to the survey are white non-Hispanic (56%), married (54%), had
      graduated from college (33%), and live in a two-parent household (60%). For 11 of
      the 15 IOF questions, the results showed that 50% or more of parents agreed with
      items on the IOF. For example, 71% of parents indicated that their family had to
      give things up as a result of their children's illnesses. Multivariate analysis
      showed that having depressive symptoms was associated with greater impact on the
      family. CONCLUSION: Our findings stress the importance of considering the needs
      of all family members when providing care to children and understanding and
      attempting to address family member's needs that may not be covered by pediatric
      palliative care services. Particular attention should be paid to parents with
      depressive symptoms, because they can receive supportive care in their children's
      pediatric palliative care programs.

PMID- 20144025
TI  - Acute bacterial suppurative thyroiditis: a clinical review and expert opinion.
AB  - BACKGROUND: Acute suppurative thyroiditis (AST) resulting from a bacterial
      infection is an infrequent but potentially life-threatening endocrine emergency.
      Traditional management of this disease has been surgery in conjunction with
      targeted antibiotic therapy. Recent nonrandomized reports of small series have
      demonstrated good outcomes using less invasive approaches. No randomized clinical
      trials have been performed. Here, we provide a review of the literature and an
      approach to this problem based on expert opinion. METHODS: The literature was
      reviewed utilizing PubMed, and a representative case of AST was presented to a
      panel of experts. Endocrinology, surgery, and infectious disease experts
      responded to a series of questions regarding diagnosis, management, prognosis,
      and harm. RESULTS: Combining a broad spectrum of clinical expertise and the
      published literature, the authors suggest a clinical algorithm as a guide to
      management, addressing both diagnosis and acute and long-term management.
      CONCLUSIONS: Published studies indicate a trend toward less invasive management
      during active inflammation and infection and regarding definite therapy.
      Remaining questions are presented to foster an evidence-based approach to this
      disease. Ideally, future randomized, controlled trials will provide data to
      improve the therapy and outcome of AST.

PMID- 20144027
TI  - Special edition: Inpatient psychiatric treatment: moving the science forward
      final.

PMID- 20144028
TI  - The role of the inpatient psychiatric nurse and its effect on job satisfaction.
AB  - This study recorded the amount of time 73 nurses working on inpatient psychiatric
      units spent on specific functions during a shift. The nurses also rated the
      amount of time they actually spent on the functions versus the amount of time
      they ideally would like to spend. Nurses spent only 2.18 minutes per shift
      teaching symptom management, and close to 2 hours on paperwork. Correlations
      between time spent in specific functions and job satisfaction indicate that
      nurses who spent more time with direct patient care were more satisfied. The
      results offer insight for increasing job satisfaction and retention/recruitment
      efforts.

PMID- 20144029
TI  - The tidal model of mental health recovery and reclamation: application in acute
      care settings.
AB  - The development, over the last decade, of the Tidal Model of Mental Health
      Recovery and Reclamation is described, and a summary of the application of the
      various Tidal processes of care is provided. Studies of evaluations of the Tidal
      Model within acute care settings are summarised and the potential contribution
      that the model makes to the development of person-centred care, within acute
      settings, is discussed.

PMID- 20144030
TI  - Violence and restraint reduction efforts on inpatient psychiatric units.
AB  - Efforts to reduce aggression and violence and the use of restraint and seclusion
      have traditionally been through some form of educational program. This paper
      presents an integrative review of research and quality improvement projects that
      aimed to reduce aggression/violence or restraint/seclusion through the use of an
      educational program. Forty-six papers are included in this review. This paper
      presents summaries and comparisons of the research designs, the content and
      length of programs, and the outcomes of these programs. From these summaries,
      trends in relation to design, content, and outcomes are identified, and
      recommendations for clinicians and researchers are given.

PMID- 20144031
TI  - Relationship between psychiatric nurse work environments and nurse burnout in
      acute care general hospitals.
AB  - Following deinstitutionalization, inpatient psychiatric services moved from state
      institutions to general hospitals. Despite the magnitude of these changes,
      evaluations of the quality of inpatient care environments in general hospitals
      are limited. This study examined the extent to which organizational factors of
      the inpatient psychiatric environments are associated with psychiatric nurse
      burnout. Organizational factors were measured by an instrument endorsed by the
      National Quality Forum. Robust clustered regression analysis was used to examine
      the relationship between organizational factors in 67 hospitals and levels of
      burnout for 353 psychiatric nurses. Lower levels of psychiatric nurse burnout was
      significantly associated with inpatient environments that had better overall
      quality work environments, more effective managers, strong nurse-physician
      relationships, and higher psychiatric nurse-to-patient staffing ratios. These
      results suggest that adjustments in organizational management of inpatient
      psychiatric environments could have a positive effect on psychiatric nurses'
      capacity to sustain safe and effective patient care environments.

PMID- 20144032
TI  - The nursing decision making process in seclusion episodes in a psychiatric
      facility.
AB  - This study explores and describes nursing interventions performed during episodes
      of seclusion with or without restraint in a psychiatric facility and examines the
      relationship between the interventions' local protocols and best-practice
      guidelines. Twenty-four nurses working in a psychiatric facility were interviewed
      about the nursing interventions they performed before, during, and after an
      episode of seclusion with or without using restraint. Analysis of the data
      reveals that the interventions meet quality standards. However, nursing practice
      would be further refined by conducting post-event reviews, especially by
      discussing how a client's aggressive behaviour is to be understood.

PMID- 20144033
TI  - Trauma informed care on an inpatient pediatric psychiatric unit and the emergence
      of ethical dilemmas as nurses evolved their practice.
AB  - Two case studies are presented reflecting the ethical dilemmas experienced by
      nurses who were striving to improve their practice in the provision of patient
      care. The cases are described in the context of finding alternatives to cohesive
      interventions such as chemical restraints and physical restraints. A summary of
      the literature on ethical dilemmas that was relevant to the issues arising in
      these cases is included. Discussion of the use of the American Nursing
      Association's (ANA, 2001 ) Nursing Code of Ethics with Interpretive Statements is
      highlighted for its relevance and support of the nurses experiencing the ethical
      dilemmas.

PMID- 20144034
TI  - Comprehensive evidence-based program teaching self-management of auditory
      hallucinations on inpatient psychiatric units.
AB  - Patients hearing command hallucinations to harm whose only self-management
      strategies are to obey these commands, can represent serious safety concerns on
      inpatient psychiatric units. A comprehensive evidence-based program teaching self
      management of auditory hallucinations on inpatient psychiatric units is described
      that includes five components: suggestions for staff education; patient self
      assessment tools; an interview guide and safety protocol; a course to teach
      strategies for managing distressing voices and commands to harm; suggestions to
      improve staff communication; and a plan to extend the program from inpatient care
      settings into the community by sharing materials with community case managers and
      caregivers when patients are discharged.

PMID- 20144035
TI  - The peer specialist movement: an interview with Gayle Bluebird, RN (interview by
      Kathleen Delaney).
AB  - In this interview, Gayle Bluebird, RN, Director of the Office of Technical
      Assistance (OTA) Center for Peer Networking, discusses the history and progress
      of the peer specialist movement. For the past 40 years, Gayle Bluebird has
      advocated for persons with psychiatric disabilities in service sectors, policy
      arenas, and with federal/state agencies. She has helped produce several important
      films and monographs on reducing seclusion and restraint. Currently her focus is
      on building a broader understanding of peer support services. This interview
      focuses on the peer specialist and the strides of peer support specialists in
      improving mental health services.

PMID- 20144036
TI  - Moods, attitudes, and presidential influence.

PMID- 20144037
TI  - "Nurses station" or "nursing station"? How to appropriately describe our work
      space in acute care?

PMID- 20144039
TI  - Shrinkage of thyroid volume in sunitinib-treated patients with renal-cell
      carcinoma: a potential marker of irreversible thyroid dysfunction?
AB  - BACKGROUND: The multitargeted tyrosine kinase inhibitor sunitinib is known to
      induce thyroid dysfunction in a substantial proportion of patients treated for
      advanced renal-cell carcinoma or gastrointestinal stromal tumors. Although
      sunitinib-induced hypothyroidism seems to be reversible in the majority of
      patients, some patients develop irreversible thyroid damage resulting in long
      lasting thyroid hormone replacement therapy. SUMMARY: We report on two cancer
      patients with a preexisting nodular thyroid gland, who developed thyroid
      dysfunction and showed marked shrinkage of the thyroid during treatment with the
      tyrosine kinase inhibitor, necessitating permanent thyroid hormone replacement
      therapy even after discontinuation of the anticancer agent. Sunitinib treatment
      in patients with a nodular thyroid can induce a significant decrease in the
      volume of the enlarged endocrine gland, associated with abnormal thyroid function
      tests leading to clinical hypothyroidism. The exact pathophysiology remains
      unknown but we discuss several possible mechanisms of sunitinib-induced thyroid
      shrinkage. CONCLUSION: Morphological changes of the thyroid gland can be
      associated with the well-described adverse biochemical effects of treatment with
      sunitinib and can be a potential marker of the irreversible organ damage.

PMID- 20144040
TI  - Visual abilities at 6 months in preterm infants: impact of thyroid hormone
      deficiency and neonatal medical morbidity.
AB  - BACKGROUND: Preterm infants are at risk for neonatal morbidity, transiently
      reduced thyroid hormone (TH) levels, and impaired visual abilities. To determine
      the interrelationship between these factors, we measured TH levels in the period
      ex utero and compared their visual abilities with those of term infants at 6
      months (corrected) of age. METHODS: The preterm group consisted of 62 infants
      stratified by gestational age: Group A (23-26 weeks, n = 10), Group B (27-29
      weeks, n = 23), Group C (30-32 weeks, n = 19), and Group D (33-35 weeks, n = 10).
      Controls were 31 healthy full-term infants. In the preterm group, free thyroxine,
      triiodothyronine, and thyroid-stimulating hormone levels were measured at 2 and 4
      weeks of life and 40 weeks postconceptional age. All infants were assessed for
      visual acuity, contrast sensitivity, and color vision using electrophysiological
      techniques. RESULTS: Compared with controls, the preterm infants demonstrated
      reduced contrast sensitivity at low temporal frequencies and slower blue-yellow
      color processing. Groups did not differ from controls in visual acuity. In the
      preterm group, reduced contrast sensitivity and slow blue-yellow and red-green
      color vision processing were associated with low TH levels, low gestational age,
      and several medical morbidities. CONCLUSIONS: Our findings signify that some of
      the weak visual abilities in preterm infants can be accounted for, in part, by
      their reduced TH levels in the early postnatal period.

PMID- 20144041
TI  - Serum chemokine (C-X-C motif ) ligand 10 levels are elevated in patients with
      Graves' disease in long-term remission.

PMID- 20144042
TI  - Escape from human monoclonal antibody neutralization affects in vitro and in vivo
      fitness of severe acute respiratory syndrome coronavirus.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) emerged as a human disease
      in 2002. Detailed phylogenetic analysis and epidemiologic studies have suggested
      that the SARS coronavirus (SARS-CoV) originated from animals. The spike (S)
      glycoprotein has been identified as a major target of protective immunity and
      contains 3 regions that are targeted by neutralizing antibodies in the S1 and S2
      domains. We previously characterized a panel of neutralizing human monoclonal
      antibodies (MAbs), but the majority of epitopes recognized by the MAbs remain
      unknown. METHODS: In the present study, we generated neutralization escape
      mutants and studied the effect of these neutralization escape mutations on human
      and animal receptor usage as well as on in vitro and in vivo fitness. RESULTS:
      Distinct but partially overlapping sets of amino acids were identified that are
      critical to the binding of MAbs with differential neutralization profiles. We
      also identified possible interactions between the S1 and S2 domains of the SARS
      CoV S glycoprotein. Finally, we showed that escape from neutralization usually
      attenuates SARS-CoV infection. CONCLUSIONS: These data provide a mechanism for
      overcoming neutralization escape by use of broadly cross-reactive cocktails of
      cross-neutralizing MAbs that recognize residues within the receptor-binding
      domain that are critical for virus replication and virulence.

PMID- 20144044
TI  - Etiology of illness in patients with severe sepsis admitted to the hospital from
      the emergency department.
AB  - BACKGROUND: Patients identified with sepsis in the emergency department often are
      treated on the basis of the presumption of infection; however, various
      noninfectious conditions that require specific treatments have clinical
      presentations very similar to that of sepsis. Our aim was to describe the
      etiology of illness in patients identified and treated for severe sepsis in the
      emergency department. METHODS: We conducted a prospective observational study of
      patients treated with goal-directed resuscitation for severe sepsis in the
      emergency department. Inclusion criteria were suspected infection, 2 or more
      criteria for systemic inflammation, and evidence of hypoperfusion. Exclusion
      criteria were age of <18 years and the need for immediate surgery. Clinical data
      on eligible patients were prospectively collected for 2 years. Blinded observers
      used a priori definitions to determine the final cause of hospitalization.
      RESULTS: In total, 211 patients were enrolled; 95 (45%) had positive culture
      results, and 116 (55%) had negative culture results. The overall mortality rate
      was 19%. Patients with positive culture results were more likely to have
      indwelling vascular lines (P = .03), be residents of nursing homes (P = .04), and
      have a shorter time to administration of antibiotics in the emergency department
      (83 vs 97 min; P = .03). Of patients with negative culture results, 44% had
      clinical infections, 8% had atypical infections, 32% had noninfectious mimics,
      and 16% had an illness of indeterminate etiology. CONCLUSION: In this study, we
      found that >50% of patients identified and treated for severe sepsis in the
      emergency department had negative culture results. Of patients identified with a
      sepsis syndrome at presentation, 18% had a noninfectious diagnosis that mimicked
      sepsis, and the clinical characteristics of these patients were similar to those
      of patients with culture-positive sepsis.

PMID- 20144045
TI  - Resistance to linezolid is mediated by the cfr gene in the first report of an
      outbreak of linezolid-resistant Staphylococcus aureus.
AB  - BACKGROUND: From April through June 2008, we identified 12 patients in the
      intensive care unit and 3 patients on other wards infected with methicillin
      resistant Staphylococcus aureus that was also resistant to linezolid. We
      investigated the mechanism of resistance--point mutations in domain V of 23S
      ribosomal RNA (rRNA) or presence of the cfr gene--involved in the outbreak.
      METHODS: Strains for the study were obtained in the intensive care unit and other
      wards. Minimal inhibitory concentrations were determined using automated methods,
      the E-test, or dilution in Mueller-Hinton agar in accordance with Clinical and
      Laboratory Standards Institute guidelines. Strains were genotyped using pulsed
      field gel electrophoresis and were sequenced to determine the presence of point
      mutations in 23S rRNA. The presence of the cfr gene was determined by specific
      polymerase chain reaction. RESULTS: The minimal inhibitory concentrations of
      linezolid ranged from 16 mg/L to 32 mg/L, and all the strains were susceptible to
      tigecycline, vancomycin, and daptomycin. Typing of strains sequentially isolated
      by pulsed-field gel electrophoresis showed that each patient carried only 1
      clonal type of linezolid-resistant, methicillin-resistant S. aureus as detected
      by sequential isolations. The presence of the cfr gene was confirmed in all the
      isolates. Furthermore, sequencing of domain V of 23S rRNA showed that the most
      common mechanism of linezolid resistance reported to date, mutation G2576T, was
      not detected in any of the strains analyzed. CONCLUSIONS: We report the presence
      of the cfr gene underlying the resistance mechanism involved in a clinical
      outbreak of linezolid-resistant S. aureus.

PMID- 20144046
TI  - Antimetabolites and cancer: emerging data with a focus on antifolates.
AB  - Antimetabolites, especially antifolates, play an important role in the treatment
      of a variety of both malignant, and non-malignant diseases, such as rheumatoid
      arthritis, and bacterial and parasitic infections. Recently, new antimetabolites
      have become an area for anticancer drug expansion. Gemcitabine has emerged as an
      important new agent in several tumour types, including non-small cell lung
      cancer, pancreatic, bladder, breast and ovarian cancers. Capecitabine is an
      intriguing new prodrug, offering tumour selectivity and prolonged tumour exposure
      to 5-FU. More potent thymidylate synthase inhibitors have also been developed;
      raltitrexed and pemetrexed are now commercially available for the treatment of
      mesothelioma, non-small cell lung cancer and other solid cancer types. This
      review will describe the most recent findings and their potential clinical
      applications.

PMID- 20144043
TI  - Susceptibility of human Th17 cells to human immunodeficiency virus and their
      perturbation during infection.
AB  - BACKGROUND: Identification of the Th17 T cell subset as important mediators of
      host defense and pathology prompted us to determine their susceptibility to human
      immunodeficiency virus (HIV) infection. METHODS AND RESULTS: We found that a
      sizeable portion of Th17 cells express HIV coreceptor CCR5 and produce very low
      levels of CCR5 ligands macrophage inflammatory protein (MIP)-1alpha and MIP
      1beta. Accordingly, CCR5(+) Th17 cells were efficiently infected with CCR5-tropic
      HIV and were depleted during viral replication in vitro. Remarkably, HIV-infected
      individuals receiving treatment had significantly reduced Th17 cell counts,
      compared with HIV-uninfected subjects, regardless of viral load or CD4 cell
      count, whereas treatment-naive subjects had normal levels. However, there was a
      preferential reduction in CCR5(+) T cells that were also CCR6 positive, which is
      expressed on all Th17 cells, compared with CCR6(-)CCR5(+) cells, in both treated
      and untreated HIV-infected subjects. This observation suggests preferential
      targeting of CCR6(+)CCR5(+) Th17 cells by CCR5-tropic viruses in vivo. Th17 cell
      levels also inversely correlated with activated CD4(+) T cells in HIV-infected
      individuals who are receiving treatment. CONCLUSIONS: Our findings suggest a
      complex perturbation of Th17 subsets during the course of HIV disease potentially
      through both direct viral infection and virus indirect mechanisms, such as immune
      activation.

PMID- 20144048
TI  - 1-acyl-4-benzyl-2,5-transdimethyl-piperazine CCR1 antagonists.
AB  - Two applications claim 1-acyl-4-benzyl-2,5-dimethylpiperazine derivatives as CCR1
      antagonists useful in the treatment of inflammatory diseases. The two
      applications respectively claim compounds in which the acyl groups are 2
      heteroaryl or cinnamoyl (and certain heterocyclic analogues thereof). Both
      applications describe compounds with good receptor affinity and good in vivo
      pharmacokinetic properties, displaying a superior profile relative to closely
      related prior art compounds.

PMID- 20144049
TI  - Muscarinic acetylcholine receptors as effector sites for present and future
      therapeutic applications: focus on non-neural cholinergic systems.
AB  - This review summarises the expression and function of muscarinic acetylcholine
      receptors (mAChR) in the organism, and the therapeutic implications of recent
      patents on cholinergic agents. Aside from the well known therapeutic applications
      of parasympathomimetic and -lytic drugs for diseases of the heart, eye,
      circulation and airways, new possible fields for mAChR agonists and antagonists
      in clinical therapy have begun to emerge. In particular, the role of non-neural
      cholinergic mechanisms in tissue regeneration, development and even
      carcinogenesis has become increasingly studied by a number of research teams
      within the last decade. This review exemplifies and contrasts experimental
      findings of mAChR drug action, and discusses these with regard to patents from
      the past 4 years.

PMID- 20144050
TI  - Thrombin receptor (PAR-1) antagonists as novel antithrombotic agents.
AB  - In addition to its central role in haemostasis and wound healing, thrombin
      activates platelets and smooth muscle cells by proteolytic activation of cell
      surface protease-activated receptor-1 (PAR-1), which is also known as the
      thrombin receptor. Thrombin is the most potent activator of human platelets and,
      as such, a thrombin receptor antagonist is likely to exert potent antithrombotic
      effect in platelet-rich arterial thrombosis. As thrombin receptor antagonism does
      not inhibit the ability of thrombin to generate fibrin, such an agent is likely
      to have less bleeding liability than conventional anticoagulants. The proof-of
      concept of the antithrombotic effect of PAR-1 antagonists has been established in
      several non-human primate models. The current success of PAR-1 research is
      underscored by the advancement of two candidates into clinical trails for acute
      coronary syndrome by Schering-Plough and Eisai Company.

PMID- 20144051
TI  - Inhibitors targeting hepatocyte growth factor receptor and vascular endothelial
      growth factor receptor tyrosine kinases.
AB  - Amgen disclosed a series of 4-heteroaryloxy quinoline/quinazoline compounds as
      multiple kinase inhibitors, including hepatocyte growth factor (HGF) receptor
      tyrosine kinase c-Met and vascular endothelial growth factor (VEGF) receptor
      tyrosine kinase. These compounds are stated to have wide therapeutic applications
      for the treatment of a variety of cancers, hypertension, arteriosclerosis,
      myocardial infarction and rheumatoid arthritis.

PMID- 20144052
TI  - Patented inhibitors (2002 - 2005) of the transcription factor NF-kappaB.
AB  - Nuclear factor-kappaB (NF-kappaB) is a central transcriptional factor and a
      pleiotropic regulator of many genes involved in immunological responses.
      Dysregulation of NF-kappaB can lead to a wide variety of diseases, including
      those related to inflammation and cancer. Therefore, NF-kappaB and the signalling
      pathways that regulate its activity have become a focal point for intense drug
      discovery and development by a number of drug companies and academic groups.
      Small-molecule inhibitors of regulatory enzymes or of NF-kappaB itself, gene
      therapy, decoy oligonucleotides or various biologicals have been reported and
      patented as potential candidates for drug development. This article reviews
      patents claiming NF-kappaB inhibitors during the period 2002 - 2005. Some of
      these inhibitors may be developed to therapeutics and used for the treatment of
      inflammatory diseases and tumour chemoresistance.

PMID- 20144053
TI  - RAF modulators and methods of use.
AB  - Exelixis claims a series of RAF kinase inhibitors based on a 3-oxo-2,3-dihydro-1H
      isoindol-1-yl core structure. Both the chemical matter and the biochemical target
      appear to be new for Exelixis, and many examples have IC(50) values < 100 nM.
      These compounds are claimed to have the potential to treat diseases that are
      associated with uncontrolled, abnormal and/or unwanted cellular activities such
      as cancer.

PMID- 20144054
TI  - Corticotropin-releasing factor receptor antagonists.
AB  - Corticotropin-releasing factor (CRF) coordinates the neural, endocrine and immune
      responses of the body to stress. Therefore, CRF receptors are important targets
      for the design of drugs for depression, anxiety and stress-related disorders.
      Several laboratories have published extensive preclinical and limited clinical
      research into the role of CRF in human disease. This review covers developments
      in the patent literature during 2002 - 2006 and outlines the prospects for CRF
      based therapy for mental illness.

PMID- 20144055
TI  - CCR5 antagonists: the answer to inflammatory disease?
AB  - Chemokines and their receptors mediate the inflammatory response during
      infectious and non-infectious disease. However, their continued activation and
      disregulation are commonly associated with chronic inflammation. Frequently,
      affected sites are characterised by inflammatory cell infiltrates expressing CC
      chemokine receptor 5 (CCR5) and high levels of CCR5 ligands. Neutralisation of
      CCR5 decreases the incidence and pathology of these diseases in murine models,
      and epidemiological studies in human patients corroborate these data. CCR5
      deficiency has been associated with increased risk of hepatic disease and
      infection, but considering the pathological effects of chronic inflammation,
      pharmacologically targeting CCR5 is still a desirable and feasible goal. The
      discovery that CCR5 is a major HIV coreceptor initiated the race to produce
      effective CCR5 antagonists. This review summarises the progress made in CCR5
      antagonist development and assesses their potential in the treatment of
      inflammatory disease.

PMID- 20144056
TI  - P2X receptor ligands and pain.
AB  - P2X receptors belong to a superfamily of ligand-gated ion channels that conduct
      the influx of Ca(2+), Na(+) and K(+) cations following activation by
      extracellular nucleotides such as ATP. Molecular cloning studies have identified
      seven subunits, namely P2X(1-7), that share approximately 40 - 50% identity in
      amino acid sequences within the subfamily. Using gene-silencing, pharmacological
      and electrophysiological approaches, recent studies have revealed roles for
      P2X(2), P2X(3), P2X(4) and P2X(7) receptors in nociceptive signalling. Homomeric
      P2X(3) and heteromeric P2X(2/3) receptors are highly localised in the peripheral
      sensory afferent neurons that conduct nociceptive sensory information to the
      spinal chord and brain. The discovery of A-317491, a selective and potent non
      nucleotide P2X(3) antagonist, provided a pharmacological tool to determine the
      site and mode of action of P2X(3)-containing receptors in different pain
      behaviours, including neuropathic, inflammatory and visceral pain. Other P2X
      receptors (P2X(4) and P2X(7)) that are predominantly expressed in microglia,
      macrophages and cells of immune origin can trigger the release of cytokines, such
      as IL-1-beta and TNF-alpha. Genetic disruption of P2X(4) and P2X(7) signalling
      has been demonstrated to reduce inflammatory and neuropathic pain, suggesting
      that these two receptors might serve as integrators of neuroinflammation and
      pain. This article provides an overview of recent scientific literature and
      patents focusing on P2X(3), P2X(4) and P2X(7) receptors, and the identification
      of small molecule ligands for the potential treatment of neuropathic and
      inflammatory pain.

PMID- 20144057
TI  - Protein kinase C: novel isozyme-selective peptide inhibitors.
AB  - Members of the protein kinase C (PKC) family play central roles in a number of
      important signal transduction pathways and are attractive targets in drug
      development for various diseases. Because of the high level of homology among its
      members, designing isozyme-specific PKC inhibitors has been extremely
      challenging. A recent patent application from the Albert Einstein College of
      Medicine describes a novel method by combinatorial modification of the substrate
      consensus sequences of an individual PKC isozyme. This approach has led to the
      identification of potent and isozyme-selective peptide inhibitors of PKCalpha,
      PKCdelta and PKCzeta.

PMID- 20144058
TI  - Novel antioxidant technology for prostate cancer chemoprevention and treatment.
AB  - The mechanisms underlying prostate carcinogenesis are not firmly elucidated. An
      exciting area of research in this regard asks whether prostate cancer results
      from the consequences of lifelong exposure of prostate tissue to oxidative
      stress. This article reviews the laboratory-based literature on oxidative stress
      and its possible role in prostate carcinogenesis. The progression of clinical
      studies focusing on the relationship between antioxidant supplementation and risk
      of developing prostate cancer are discussed, along with the patent literature
      since 2003 involving novel antioxidant technology applicable to prostate cancer
      prevention and treatment. In particular, recently published in vitro experiments
      with a novel alpha-tocopherol analogue, 2,2,5,7,8-pentamethyl-6-chromonal, which
      characterised its unique spectrum of antioxidant and antiandrogen properties in
      prostate cancer cell lines, is discussed. In addition, recent patent applications
      and supporting findings from the literature surrounding: i) cisplatin tocopherol
      compounds; ii) coix seed soft capsules with vitamin E; iii) vitamin E succinate
      (alpha-tocopheryl succinate); iv) lycopene preparations with other carotenoids;
      v) compounds of the ginger family; vi) novel aryl-carbaldehyde oxime derivatives;
      vii) novel phenyl quinoline derivatives; and viii) resveratrol, its derivatives
      and preparations thereof are discussed as they relate to prostate cancer
      chemoprevention and treatment.

PMID- 20144059
TI  - Long-acting muscarinic M3 receptor antagonists.
AB  - Two applications claim a novel class of muscarinic M(3) receptor antagonists and
      their use as long-acting agents for the treatment of chronic obstructive
      pulmonary disease. The two applications claim closely related structures with one
      claiming quaternary amine salts of the tertiary amines claimed in the other. The
      claimed compounds comprise a biarylmethylamine core with the amino group modified
      by acylation or sulfonation and a tertiary or quaternary amine coupled to the
      distal ring of the biaryl system.

PMID- 20144060
TI  - Long-acting muscarinic M3 receptor antagonists.
AB  - A series of 10 closely related patent applications define Theravance's approach
      to the development of long-acting M(3) selective antagonists for the treatment of
      chronic obstructive pulmonary disease. The applications illustrate a modular
      approach to the design of such agents, comprising a muscarinic pharmacophore
      attached to a second, less functionalised moiety via a variable length spacer
      incorporating heteroatoms. Eight of the applications utilise a a 4
      piperidinylester of biphenylcarbamic acid as the muscarinic pharmacophore and two
      utilise 2,2-diphenyl-2-(S)-pyrrolidin-3-ylacetamide. The first group of eight
      applications encompasses the use of two tail groups and four different sets of
      linking groups, whereas the second uses two very different tail groups and
      different spacers.

PMID- 20144061
TI  - Dual-acting beta2 agonists/muscarinic antagonists.
AB  - Bifunctional aromatic derivatives that act as both beta(2) agonists and
      muscarinic receptor antagonists are claimed. The compounds use two separate
      pharmacophoric groups, coupled by a long lipohilic chain, to provide the desired
      biological activities and with the aim of providing a long duration of action.
      The compounds are claimed to be useful in the treatment of both asthma and
      chronic obstructive pulmonary disease and represent the first disclosure of a new
      concept - muscarinic antagonist-beta(2) agonists.

PMID- 20144062
TI  - Dissociated non-steroidal glucocorticoids: tuning out untoward effects.
AB  - The endogenous glucocorticoid (GC), cortisol, is involved in maintaining
      homeostatic balance in glucose regulation and immune response while allowing
      stress adaptation. The glucocorticoid receptor (GR) is required to maintain life
      and is the target of numerous FDA-approved drugs. Synthetic steroidal GCs are
      useful in a plethora of conditions characterized by excessive inflammatory or
      immune responses. Unfortunately, the GCs used at present have potentially dose
      limiting and debilitating side effects, some of which derive from the glucose
      regulatory role of GCs. Consequently, there is a great need to find agents which
      preserve the potent immune effects without the side effects. This manuscript
      reviews the existing patent literature on these intensely sought non-steroidal
      agents that dissociate the therapeutic from metabolic effects, or specifically
      retain certain GR target effects with attenuated untoward effects. The chemical
      classes and underlying mechanisms (when known) for these non-steroidal GCs are
      discussed.

PMID- 20144063
TI  - Non-steroidal glucocorticoid receptor antagonists: the race to replace RU-486 for
      anti-glucocorticoid therapy.
AB  - The endogenous glucocorticoid, cortisol, elevates blood glucose and suppresses
      the immune system. Glucocorticoid (GC) levels rapidly increase in response to
      physiologic and mental stress, thereby allowing stress adaptation. Unfortunately,
      the GC response can be excessive, especially under stressful conditions for the
      organism. The resulting hypercortisolemia is associated with a cluster of
      symptoms called Cushing's syndrome, a serious and potentially fatal illness
      involving hyperglycemia, hypertension, osteoporosis, muscle atrophy and fat
      maldistribution, as well as psychoses and immunosuppresion. Several disease
      states, such as diabetes and Cushing's, would benefit from blocking the actions
      of endogenous cortisol. The only glucocorticoid receptor (GR) antagonist
      available in the clinic is the steroid mifepristone (RU-486), whose primary
      potency is antigestagenic, making its utility as a GR antagonist limited. This
      manuscript reviews the current patent literature on selective non-steroidal GR
      antagonists.

PMID- 20144064
TI  - Recent advances in the development of histamine H3 antagonists.
AB  - The histamine H(3) receptor is involved in the central and peripheral regulation
      of levels of histamine and other neurotransmitters (e.g., acetylcholine,
      noradrenaline, dopamine, serotonin and GABA), which sets it up as a target in the
      treatment of various CNS (e.g., depression, schizophrenia, ADHD, dementia,
      neuropathic pain and sleep disorders), metabolic syndrome (e.g., obesity) and
      allergic disorders. Novel chemical series from the most recent 2 years of patent
      literature have been reviewed. While overall structural diversity is moderate,
      these represent or relate to some of the compounds progressing through clinical
      trials (e.g., GSK-189254). However, an H(3) receptor drug still has yet to reach
      the market. Patenting activity is likely to remain high in the near future,
      bolstered by the commercial promise of potential H(3) receptor drugs.

PMID- 20144065
TI  - Enhanced selective serotonin re-uptake inhibitors as antidepressants: 2004 -
      2006.
AB  - Depression is a major psychiatric disorder. It affects millions of people
      worldwide and inflicts tremendous economic burden on societies. The advent of
      selective serotonin re-uptake inhibitors as antidepressants has been a
      revolutionary advance in the treatment of depression and related disorders.
      However, selective serotonin re-uptake inhibitors are also associated with
      several undesirable properties, such as delayed onset of action, low response
      rate and side effects. The present search for a newer generation of
      antidepressants is focused on overcoming these issues. The patent literature
      covered in this review, during 2004 - 2006, illustrates several strategies
      employed by the pharmaceutical industry in the development of enhanced serotonin
      re-uptake inhibitors. Encouraged by the success of venlafaxine and duloxetine,
      several companies have pursued dual-acting serotonin and noradrenaline re-uptake
      inhibitors as drug candidates for depression treatment. Molecules with combined
      serotonin re-uptake inhibitor and 5-HT autoreceptor (5-HT(1A) and/or 5-HT(1B))
      antagonist properties are being developed. In particular, recent research
      suggests that serotonin 5-HT(1B) antagonists alone or combined with selective
      serotonin re-uptake inhibitors might hold unique promise as efficacious
      antidepressants. Finally, efforts are underway to formulate new drug candidates
      with both serotonin re-uptake inhibitor and neurokinin 1 (NK(1)) antagonist
      activities. Despite mixed results from clinical trials with several NK(1)
      antagonists, effective therapeutic agents for depression may still emerge from
      compounds with combined serotonin reuptake inhibitor/NK(1) antagonist properties.

PMID- 20144066
TI  - Renoprotective effect of calcium channel blockers in combination with an
      angiotensin receptor blocker in elderly patients with hypertension. A randomized
      crossover trial between benidipine and amlodipine.
AB  - Anti-hypertensive medication with an angiotensin II receptor blocker (ARB) is
      effective in slowing the progression of chronic kidney disease. The present study
      was designed to investigate whether calcium channel blockers (CCBs) in
      combination with an ARB differentially affect kidney function. Elderly
      hypertensive patients with chronic kidney disease (n = 17, 72 +/- 6 years old)
      were instructed to self-measure blood pressure. They were randomly assigned to
      receive either benidipine (4-8 mg/day) or amlodipine (5-10 mg/day) combined with
      olmesartan (10 mg/day). After 3 months, CCBs were switched in each patient and
      the same protocol was applied for another 3 months. At baseline, significant
      correlation was obtained between urine albumin (22.8 +/- 16.7 (median +/- median
      absolute deviation) mg/g creatinine) and self-measured blood pressure (170 +/-
      23/87 +/- 10 (mean +/- SD) mmHg, r = 0.65, p < 0.01). Both regimens reduced blood
      pressure to a similar extent (139 +/- 22/75 +/- 11 mmHg and 133 +/- 17/72 +/- 10
      mmHg, respectively; both p < 0.001), while urine albumin decreased only after
      combination therapy including benidipine (11.7 +/- 6.1 mg/g creatinine, p <
      0.05). Benidipine, but not amlodipine, in combination with olmesartan, reduced
      urinary albumin excretion in elderly hypertensive patients with chronic kidney
      disease. The results suggest the importance of selecting medications used in
      combination with ARB in hypertensive patients with chronic kidney disease.

PMID- 20144067
TI  - Seasonal blood pressure variation and its relationship to environmental
      temperature in healthy elderly Japanese studied by home measurements.
AB  - The purpose of the present study was to examine seasonal blood pressure variation
      and its relationship to environmental temperature in healthy elderly Japanese, as
      studied by home measurements. Fifteen healthy elderly Japanese (79.3 +/- 5.9 yrs)
      measured their blood pressure at home each morning for more than 25 times per
      month for 3 years. Monthly mean outdoor temperatures were obtained from the
      Takamatsu meteorological Observatory. The highest levels of systolic and
      diastolic blood pressure measured at home were observed in February (129 +/- 14
      and 81 +/- 13 mmHg). The lowest levels of systolic and diastolic blood pressure
      measured at home were observed in August (117 +/- 11 and 73 +/- 10 mmHg).
      Likewise, the lowest and highest means of outdoor temperature were observed in
      February (5.0 degrees C) and August (29.2 degrees C), respectively. Hence, both
      systolic and diastolic blood pressure demonstrated a close inverse correlation
      with the means of outdoor temperature (r = -0.973, p < 0.001 and r = -0.985, p <
      0.001, respectively). A 1 degree C decrease in the mean outdoor temperature was
      associated with rises of 0.43 mmHg in systolic blood pressure (SBP) and 0.29 mmHg
      in diastolic blood pressure (DBP). Seasonal variations in home blood pressure and
      outdoor temperature showed complete correspondence in healthy elderly Japanese,
      with the blood pressures being inversely related to the ambient temperature.
      These seasonal home blood pressure variations should be kept in mind when
      controlling blood pressure in elderly patients.

PMID- 20144068
TI  - Relationship between high density lipoprotein antioxidant activity and carotid
      arterial intima-media thickness in patients with essential hypertension.
AB  - The objective of this study was to evaluate high-density lipoprotein (HDL)
      antioxidative activity and its possible influencing factors in patients with
      essential hypertension and to investigate the correlations between HDL
      antioxidative activity and the carotid arterial intima-media thickness (CIMT).
      Thirty-three patients with essential hypertension and 32 healthy people as
      control were included. High- and low-density lipoprotein in plasma were isolated
      by one-step density gradient ultracentrifugation, and induced oxidation with
      external Cu(2+). Antioxidant activity of HDL, lag time, and lipid peroxidation
      degree were determined by spectrophotometric and thiobarbituric acid reactive
      substances (TBARS) methods. Paraoxonase 1 (PON1) activity in serum was measured
      with continuous monitoring using phenylacetate as a substrate. The CIMT was
      measured with a high-resolution ultrasound Doppler system. In patients with
      essential hypertension, the inhibitory effect of HDL on low-density lipoprotein
      (LDL) oxidation and the PON1 activity were reduced (72.29 +/- 2.03)% vs. (80.91
      +/- 2.06)%, and (112.21 +/- 8.64)u/ml vs. (146.43 +/- 8.79)u/ml (all P < 0.05).
      The lag time of oxidation and the lipid peroxidation between the hypertensive
      group and the control group did not show a statistically significant difference.
      Multiple stepwise regression analysis revealed that HDL antioxidative activity
      might be affected by PON1 activity (P = 0.004), diastolic pressure (P = 0.004),
      sex (P = 0.006), and that CIMT might be affected by HDL antioxidative activity (P
      = 0.030), systolic pressure (P = 0.026), and total cholesterol level (P = 0.033).
      The HDL antioxidative activity is reduced in patients with essential hypertension
      and significantly affected by sex. The CIMT was negatively correlated with HDL
      antioxidative activity, which suggests that decreased HDL antioxidative activity
      may be one of the important determinants for the development of atherosclerosis
      in patients with essential hypertension.

PMID- 20144069
TI  - Beneficial effect of combination therapy comprising angiotensin II receptor
      blocker plus calcium channel blocker on plasma adiponectin levels.
AB  - The study aim was to examine the effect of combination therapy comprising
      angiotensin receptor blocker plus calcium antagonist on post-treatment plasma
      adiponectin levels compared to pretreatment levels. There was a significant
      gender difference in the relationship between preadiponectin level and age. In
      the search for contributing factors for treatment-based changes in adiponectin
      levels, these effects of gender and age were considered in statistical analysis.
      The adiponectin level in the combination therapy group was further increased
      compared to that in each of the monotherapy groups, despite there being no
      significant difference in antihypertensive effect, indicating that the combined
      medication provided an effect beyond that of lowering blood pressure.

PMID- 20144070
TI  - The relationship between endothelial damage and aortic augmentation index.
AB  - Augmentation index (AIx), a measure of wave reflection, is regulated by a number
      of factors, including endothelial function and vascular smooth muscle tone. The
      relationship between local endothelium-derived factors and AIx is well known;
      however, association between endothelial damage markers and AIx has not been
      sufficiently studied. This study investigates whether endothelial damage markers
      von Willebrand factor (vWF) soluble thrombomodulin (sTM)--are associated with
      wave reflections. We studied 46 (48.5 +/- 10.6, years) never-treated patients
      with hypertension (HT) and an age-matched control group of 40 (47 +/- 8.6, years)
      normotensive individuals. von Willebrand factor and sTM levels were determined in
      all subjects. We evaluated the aortic AIx of the study population using
      applanation tonometry (Sphygmocor, AtCor Medical, Sydney, Australia). The heart
      rate-corrected augmentation index (AIx@75) was estimated as a marker of wave
      reflections. Endothelial damage markers and AIx@75 were significantly higher in
      hypertensive patients than in controls. In the whole population, the vWF level
      (beta = 0.24, p = 0.01) was an independent determinant of AIx@75 in multivariate
      analysis. However, the sTM level was not associated with AIx@75. We found that
      the vWF level was an independent determinant of AIx@75. Our results suggest that
      increased an vWF level contributes significantly to increased wave reflections.

PMID- 20144071
TI  - The role of fixed-dose combination therapy with drugs that target the renin
      angiotensin system in the hypertension paradigm.
AB  - Most patients with hypertension require two or more agents from different classes
      to achieve BP control. Several fixed-dose combinations are available, often
      combining agents that target the renin angiotensin system (angiotensin-converting
      enzyme [ACE] inhibitors or an angiotensin receptor blockers [ARBs]) plus either
      thiazide diuretics or calcium channel blockers (CCBs). At low doses, these
      combinations may have greater efficacy and better tolerability than the
      respective high dose monotherapies. Combining an ARB (instead of an ACE
      inhibitor) with the CCB amlodipine offers efficacy with improved tolerability.
      This review aims to highlight the simplicity, tolerability, and convenience of
      fixed-dose combinations targeting the renin-angiotensin system, which can lead to
      improved compliance and more patients achieving BP goals.

PMID- 20144072
TI  - Increased levels of asymmetric dimethylarginine and C-reactive protein are
      associated with impaired vascular reactivity in essential hypertension.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide
      synthase and has been implicated in endothelial dysfunction. We sought to assess
      weather inflammation is involved in the impaired vascular reactivity induced by
      ADMA in essential hypertension. Brachial artery flow-mediated dilation (FMD),
      serum ADMA, and C-reactive protein were determined in 71 never-treated
      hypertensive patients. Serum ADMA was related directly to C-reactive protein and
      reversely to FMD. In multiple regression analysis, ADMA was the only independent
      determinant of FMD. Probably, the chronic inflammation documented in these
      patients may be considered the mechanistic link between ADMA and vascular damage.

PMID- 20144073
TI  - Effect of revised UPPP surgery on ambulatory BP in sleep apnea patients with
      hypertension and oropharyngeal obstruction.
AB  - This study aimed to investigate the value of the surgery of revised
      uvulopalatopharyngoplasty (UPPP) on ambulatory blood pressure (BP) in obstructive
      sleep apnea/hypopnea syndrome (OSAHS) patients with hypertension and
      oropharyngeal obstruction. A retrospective cohort study was performed in 29
      patients with OSAHS and hypertension, who received treatment with revised UPPP
      surgery. After surgery 1 month, the Apnea-hypopna index (AHI) and body mass index
      (BMI) significantly decreased (P < 0.05), and mini SpO(2) and mean SpO(2)
      increased than before (P < 0. 05), but the heart rate showed no significant
      difference (P > 0.05). In the meantime, compared to pretreatment, nighttime
      systolic SBP, nighttime diastolic DBP, morning systolic SBP, morning diastolic
      DBP, 24-h DBP, and 24-h SBP, decreased significantly (P < 0.05), but daytime SBP
      and daytime DBP showed no significant difference (P > 0.05). The results of this
      study indicated that the BP in the sleep apnea patients with hypertension might
      gradually decrease by revised UPPP surgery.

PMID- 20144074
TI  - Higher levels of plasma TNF-alpha and neuropeptide Y in hypertensive patients
      with obstructive sleep apnea syndrome.
AB  - Resistant hypertension is always fount to be accompanied with obstructive sleep
      apnea syndrome (OSAS). Previous studies assumed inflammation participated in OSAS
      and hypertension. The fact that tumor necrosis factor a (TNF-alpha) was related
      to OSAS, while neuropeptide Y (NPY) was related to hypertension, was widely
      reported separately. To investigate the involvement of TNF-alpha and NPY
      simultaneously in hypertension accompanied with OSAS, 417 subjects who underwent
      the polymonograph and blood pressure measurement were consecutively selected.
      Plasma TNF-alpha and NPY levels were determined in normotensive with OSAS (n =
      113), hypertensive without OSAS (n = 73), hypertensive with OSAS (n = 134), and
      those of controls (n = 97), respectively. A significant increase of plasma TNF
      alpha and NPY were both observed in hypertensive subjects with or without OSAS,
      the highest level of TNF-alpha and NPY were in hypertension with the OSAS group.
      TNK-alpha, NPY, and neck circumference contributed to OSAS and hypertension as
      risk factors in the logistic regression model. Neck circumference was impacted by
      apnea/hyponea index, mean diastolic blood pressure, and TNF-alpha level, which
      was indicated via the multiple linear model. The present study indicated a
      positive interplay between plasma TNF-alpha, NPY, hypertension, and OSAS in the
      Han population of Xinjiang. Although there is evidence that inflammation plays a
      role in the pathophysiology of hypertension and OSAS, clear evidence is still
      lacking, and raises the dilemma of the hen and the egg. Further studies are
      needed to clarify the role of inflammation in the pathogenesis of hypertension
      with OSAS, in which neck size should be considered as a linked independent
      factor.

PMID- 20144075
TI  - Increased ET-1 and reduced ET(B) receptor expression in uremic hypertensive rats.
AB  - The endothelin-1 (ET-1) system has been implicated in cardiovascular disease
      associated with chronic renal failure. We investigated the expression and
      localization of ET-1 and the ET(B) and ET(A) receptors in vascular and renal
      tissues of uremic hypertensive rats. Uremia was induced by renal artery branches
      ligation. At week 6, blood and renal parameters, and plasma and urine ET-1 levels
      were evaluated. The ET-1, and the ET(B) and ET(A) receptors expression and
      localization were determined by Northern and Western blotting, and by
      immunofluorescence, respectively. Blood pressure, serum creatinine, proteinuria,
      and urinary ET-1 were increased in uremic rats. The ET-1 expression was increased
      in the aorta, mesenteric arteries, and the renal cortex of uremic rats, whereas
      the ET(B) receptor expression was reduced. Immunofluorescence analysis using the
      thoracic aorta revealed that the endothelial ET-1 levels were increased 4-fold in
      uremic rats. In contrast, the ET(B) receptor expression, which was localized
      exclusively in the endothelium, was markedly reduced. The ET(A) receptor
      expression, however, was increased 1.6-fold and was detected in the media only.
      Similar changes in ET-1 and ET(B) receptor expression were observed in renal
      cortex vessels and glomeruli of uremic rats. This study reveals that ET-1 levels
      are augmented in the vascular endothelium of uremic rats, whereas the ET(B)
      receptor expression is reduced which may play a major role in hypertension and
      renal failure progression.

PMID- 20144076
TI  - Specific language impairment in Turkish: evidence from case morphology in Turkish
      German successive bilinguals.
AB  - Language disorders, and Specific Language Impairment (SLI), have been extensively
      studied in a number of different, though thus far almost exclusively
      Indoeuropean, languages. For other languages such as Turkish, Vietnamese, or
      Arabic, however, findings on the outcome of SLI are rare. In this context, the
      growing number of migrant children in European countries with a variety of first
      languages can be seen as a challenge to linguistics and to language assessment:
      The lack of empirical findings on SLI in these languages brings up the question
      of how the impairment is manifested in bilingual children with a migrant
      background. In order for a language disorder to correctly be labelled SLI, it
      needs to be identified in both languages. This paper presents findings from a
      study examining the grammatical features of Turkish first language acquisition in
      Germany, while focusing on Turkish case morphology. For this purpose, it compares
      the data of three typically-developing children and two children with deviant
      language development. Moreover, it presents a first interpretation of the outcome
      of grammatical SLI in bilingual Turkish children and discusses suggestions for
      diagnostic assessment procedures.

PMID- 20144077
TI  - Sonority and the acquisition of /s/ clusters in children with phonological
      disorders.
AB  - The structure of /s/-clusters has been a rather controversial subject due to
      their structural oddities. Studies on the acquisition of these clusters have
      contributed to the discussion to validate certain theoretical claims, and
      sonority-related issues have always been in focus. Cross-linguistic acquisition
      data from children with phonological disorders can provide further testing ground
      for several unsettled matters regarding their syllabification.

PMID- 20144078
TI  - Acquisition of /s/ clusters in English-speaking children with phonological
      disorders.
AB  - Two member onset consonant clusters with /s/ as the first member (#sC onsets)
      behave differently from other double onset consonant clusters in English.
      Phonological explanations of children's consonant cluster production have been
      posited to predict children's speech acquisition. The aim of this study was to
      consider the role of the Sonority Sequencing Principle (SSP), homorganicity,
      headedness, and factorial typology in the explanation of productions of consonant
      clusters by children with phonological disorders. Thirty monolingual English
      speaking children with phonological disorders produced words commencing with #sC:
      /s/+stop (/sT/), /s/+nasal (/sN/), /sl/, and /sw/. There was wide individual
      variation between participants. Overall, there was an increase in accuracy of
      consonant cluster production as the sonority indices of the second element of the
      cluster increased: there was significantly greater accuracy of /sl/ than /sN/ and
      significantly greater accuracy of /sN/ than /sT/. However, /sw/ targets only
      followed the SSP for phonologically accurate (but not phonetically accurate)
      productions. Correct renditions justified the binary grouping of the SSP
      following vs SSP-violating separation. Homorganicity of the cluster was not a
      factor in determining relative accuracy of the targets. The percentage of correct
      renditions justified the /s/+[-continuant] vs /s/+[+continuant] binary
      separation. There were several counterexamples of predictions of the headedness
      approach. Thus, sonority and factorial typology were found to be useful in
      predicting /s/ consonant cluster acquisition of children with phonological
      disorders.

PMID- 20144079
TI  - Acquisition of /s/-clusters in Spanish-English bilingual children with
      phonological disorders.
AB  - This study investigated the development of English two-member onset #sC clusters
      in Spanish-English bilingual children with phonological disorders. Data from 30
      children were analysed in terms of correct and incorrect productions,
      implicational relationships, and possible groupings according to the sonority
      index of the second member of the cluster. While a great deal of variability
      occurred both within and across children, a number of general findings did occur.
      Sonority sequencing was found to be relevant in accurate renditions. Also
      justifiable was the binary grouping of /s/+[-continuant] vs /s/+[+continuant].
      With regard to reduction patterns, the predictions of factorial typology were
      found to be useful.

PMID- 20144080
TI  - Acquisition of /s/-clusters in Dutch-speaking children with phonological
      disorders.
AB  - This study investigated the acquisition of word initial /s/ clusters of 3-5 year
      old Dutch children with phonological disorders. Within these clusters, /sl/ was
      produced correctly most often, whereas /sn/ and /sx/ were the more difficult
      clusters. In cluster reductions, /s/+obstruent and /sl/ clusters reduction
      patterns followed the Sonority Sequencing Principle (SSP) by retaining the least
      sonorous segment; but this is not the case for the /sm/ cluster, where the more
      sonorous element is retained. The predictions of the factorial typology are
      supported. Reductions seem explainable through an interaction between sonority
      and the prosodic head of the cluster. Exceptions are /sn/ and /sx/, where no
      consistent reduction patterns are found. As expected, word production of children
      with phonological disorders is far less target-like than that of typically
      developing children. However, the patterns of phonological simplification and
      reduction of the two groups are surprisingly similar. It can be concluded that
      language development of children with phonological disorders is delayed rather
      than deviant.

PMID- 20144081
TI  - Acquisition of /s/-clusters in Hebrew-speaking children with phonological
      disorders.
AB  - This study examines the production and reduction patterns of initial /s/ clusters
      by Hebrew-speaking children with phonological disorders. Data were collected from
      30 children with phonological disorders between the ages of 3;5-5;2. The data
      were elicited by means of a picture-naming task combined with a sentence
      completion task. Target words consisted of initial clusters, including #sC and
      #CC clusters. Results revealed that the percentage of correct productions of
      /s/+approximant clusters were significantly lower than those of the correct
      productions of other /s/ clusters. The differences between /s/+approximant
      clusters and the other /s/ clusters also emerged in the reduction patterns, where
      clusters from the first group were reduced to C1 but clusters from the second
      group were reduced to C2. There were no differences in the correct productions
      between the productions of SSP-violating clusters and the SSP-following clusters.

PMID- 20144082
TI  - Acquisition of /s/ clusters in Croatian speaking children with phonological
      disorders.
AB  - The authors studied the acquisition of nine #sC clusters in 30 Croatian-speaking
      phonologically disordered children, aged between 3;8-7;0 years, by analysing
      their renditions of target words elicited in response to visual stimuli presented
      on a computer screen. Results did not support the idea that a greater jump in
      sonority from C1 to C2 would translate into a greater accuracy of productions.
      The percentage of correct realizations was high for /s/+nasal combinations (mean
      85%), and for approximants /j/ and // (mean 77%) and stops (mean 73%), with
      significantly lower scores for liquids /l/ and /r/ (mean 47%). The difference
      between SSP-violating and SSP-following targets was not significant, and neither
      was the homorganicity of the target. The most frequent errors were substitution
      of the first consonant (i.e. /s/) while keeping the second one. These children
      are significantly different from the typically-developing group in two ways.
      First, retention of the first or the second consonant is not as frequent, and,
      second, /l/ is almost as difficult as /r/, as opposed to the typically-developing
      children who had no more difficulty with /l/ than with the other two
      approximants. Although cluster reduction is not the most common process in
      erroneous productions, the patterns emerged here generally agree with the
      findings from other languages.

PMID- 20144083
TI  - Epilogue.
AB  - Cross-linguistic findings in the acquisition of /s/-clusters in children with
      phonological disorders revealed some shared features among languages as well as
      raised some language-specific issues. While in correct production of the targets
      more variation was observed among language groups, more uniform behaviour was
      found across languages in cluster reductions, which were the most common
      processes in erroneous productions.

PMID- 20144084
TI  - Therapeutic potential of adenosine receptor antagonists and agonists.
AB  - The adenosine receptors (A(1), A(2A), A(2B) and A(3)) are important and
      ubiquitous mediators of cellular signalling, which play vital roles in protecting
      tissues and organs from damage. Launched drugs include the adenosine receptor
      antagonists theophylline and doxofylline (both used as bronchodilators in
      respiratory disorders such as asthma), while several compounds are presently in
      clinical trials for a range of indications, including heart failure, Parkinson's
      disease, rheumatoid arthritis, cancer, pain and chronic obstructive pulmonary
      disease. A host of companies and institutions are addressing the huge potential
      for the development of selective adenosine receptor agonists and antagonists, so
      that it appears we are on the verge of a new wave of compounds approaching the
      market for many unmet medical needs. This review presents an analysis of the
      patenting activity in the area for 2006 and an interpretation and reflection on
      the developments that we can expect in the future.

PMID- 20144085
TI  - Trends in therapeutic monoclonal antibodies of cancer.
AB  - Therapeutic monoclonal antibodies are increasingly applied in clinical
      application with great success. A variety of antibody products have been approved
      by the FDA since 1997. Furthermore, the industries have been paying more
      attention to and efforts in the field of antibody development than ever,
      suggesting the grand potential of the market and benefits. At present, many
      monoclonal antibodies have proven their therapeutic value in combination with
      established treatment for many diseases, as shown in FDA approved expanded
      indications. This old-fashioned immunotherapy exerts profound effects in many
      refractory and formidable diseases, especially cancers. With further
      understanding of the interaction between immune system and cancer, more target
      molecules were discovered and more promising therapeutic antibodies with improved
      effects will be feasible in the future. Regardless of initial development or
      ultimate approved drug, therapeutic monoclonal antibodies have always been
      associated with numerous patent applications. This review mainly focuses on
      potential therapeutic monoclonal antibodies in oncology and related antibody
      patents, and discusses the trend for antibody development and therapeutic
      applications in humans.

PMID- 20144086
TI  - Adenovirus-vectored vaccines.
AB  - BACKGROUND: Engineered adenoviruses are being increasingly explored as
      immunoprophylactic or immunotherapeutic vaccine vectors. Encouraging data from
      preclinical studies using human adenovirus vectors carrying different antigen
      genes have resulted in many currently ongoing clinical trials. OBJECTIVE: The
      article seeks to review the current status of the use of adenoviruses as vaccine
      vectors. METHODS: This review is based on the patent literature since 2000
      pertaining to the development of adenovirus vaccine vectors for infectious and
      non-infectious diseases. CONCLUSION: Human adenovirus-vectored vaccines have
      important limitations that stem from their immunogenicity and restrict their
      utility. This has spurred intensive efforts to find alternative adenovirus
      vectors and strategies, each with its own advantages and shortcomings.

PMID- 20144087
TI  - 7S and 19S Isoagglutinins in Systemic Lupes Erythematosus.
AB  - The 7S and 19S distribution of blood group isoantibodies (isoagglutinins) has
      been measured in patients with systemic lupus erythematosus. The only possibly
      significant finding was a lower level of macroglobulin isoagglutinin to B cells
      in patients of blood type A. This is consistent with previous findings of
      lessened response to bacterial antigens by the macroglobulin antibody.

PMID- 20144088
TI  - A double blind trial with cartilage and bone marrow extract in degenerative
      gonarthrosis.
AB  - A double-blind trial with cartilage and bone-marrow extract (Rumalon A) and
      placebo (Rumalon B) was carried out on 106 patients with degenerative bilateral
      gonarthrosis. Favorable results were obtained in 64% of the patients treated with
      Rumalon A and in only 29% of the placebo group. This difference is statistically
      significant (p < 0.05). The slight influence of placebo can be related to the
      psychosomatic effect of injections and/or coincident spontaneous improvement of
      the gonarthrosis. Cartilage and bone marrow extract increases the therapeutic
      possibilities in degenerative joint disease. It is easy to administer and
      practically without side effects.

PMID- 20144089
TI  - Synovectomy of the metatarsophalangeal joints in rheumatoid arthritis.
AB  - Synovectomy of II-V mtp-joints was performed on 33 feet in 28 patients. The
      average follow-up time was 15 months. The results were evaluated with respect to
      pain, radiographic changes, and the patients' own estimate. Radiographic
      appearances were compared with the unoperated joints in the other foot. The
      radiographic changes were also correlated with changes in the general activity of
      the disease.

PMID- 20144090
TI  - Prevalence of rheumatoid arthritis in densely and thinly populated areas in
      sweden.
AB  - The prevalence of rheumatoid arthritis in 1,287 persons living in densely
      populated areas and 1, 287 persons living in thinly populated areas, matched as
      to sex, age, occupation and geographical area, was compared. The patient material
      was obtained in an epidemiological survey of rheumatoid arthritis (ARA
      definition) performed in Sweden in 1961. 1.6% of the inhabitants in densely
      populated areas and 2.5% in thinly populated areas had rheumatoid arthritis
      (classical, definite, probable, possible). The differences were indicative but
      not significant. Classical plus definite rheumatoid arthritis, however, showed
      exactly the same prevalences in the two populations (0.5%). Probable plus
      possible rheumatoid arthritis was indicatively more prevalent in the thinly
      populated areas (2.0%) than in the densely populated (1.1%).

PMID- 20144091
TI  - Arthritis Induced with Freund's Adjuvant and its Relationship to Changes in the
      Stomach, Small Intestine and Thymus: A Histological and Tritiated Thymidine Study
      on Rats.
AB  - The aim of the study was to elucidate histological changes provoked by
      Mycobacterium butyricum toxine in the rat joints, stomach, small intestine and
      thymus and the uptake of tritiated thymidine. Freund's complete adjuvant was
      injected into the base of the vastus muscle of 35 rats; 21 rats served as
      controls. Fifteen rats displayed histologically mild synovitis in the ankle
      joint, two periostitis and three muscle infiltrates. Histological study revealed
      no difference between the test animals and the controls in the stomach, small
      intestine and thymus. The thymidine uptake of the adjacent growth lines of the
      knee, stomach mucosa, small intestine, spleen and liver was the same in both
      groups. In contrast, the uptake of the cells of the thymus was smaller in the
      adjuvant-treated rats with a probability of over 90 per cent. This suggests that
      the mitosis of adjuvant-induced thymic cells is smaller than in cells with a
      normal condition.

PMID- 20144092
TI  - Some aspects of epidemiology and surveillance of rheumatic Fever.
AB  - The aim of the study was to find the most reliable and precise incidence of
      rheumatic fever attacks in the general population. All new cases of rheumatic
      fever were recorded in an area of 100, 000 population. The frequency of first
      attacks and recurrences decreased from 53 per 100, 000 inhabitants to 15 in 1968.
      Less pronounced was the fall in the incidence of first attacks. The prevalence of
      rheumatic heart diseases in the studied group of patients was relatively low.
      Epidemiological studies are one of the most important components of the
      surveillance of rheumatic fever. Further important tasks are early diagnosis and
      hospitalization, introduction of adequate therapy and (effective) prophylactic
      measures, with periodic checkups.

PMID- 20144093
TI  - Involvement of the manubrio-sternal articulation in rheumatoid arthritis.
AB  - Changes in the manubrio-sternal articulation (MSA) were examined radiologically
      in 87 patients with rheumatoid arthritis and in a control group comprised of 23
      patients with osteoarthritis and 72 subjects without joint disease. Erosions,
      reactive sclerosis and ankylosis were encountered in 70% of the rheumatoid
      arthritis group and in 27% of controls. There was no difference in the incidence
      of changes in persons with osteoarthritis and in the other control subjects.

PMID- 20144094
TI  - Studies on the sicca syndrome in patients with rheumatoid arthritis.
AB  - Secretion from the parotid and the lacrimal glands has been studied in two
      similar groups of 48 subjects, one consisting of RA patients, the other a control
      group. Sialometry and sialography has been performed as regards the parotid
      glands; the secretion of the lacrimal glands has been measured with Schirmer's
      test I and the occurrence of conjunctival and corneal epithelial defects
      stainable with Rose-Bengal has been studied. It has been shown that lacrimal and
      parotid secretion was significantly reduced in the RA group as compared with the
      control group; that epithelial defects typical for KCS occurred significantly
      more often in the RA group; that parenchymal changes, sialodochiectasias, existed
      in the RA group but that sialodochiectasias were completely absent in the control
      group; that there was no significant co-variation in the RA group between
      lacrimal and salivary secretion or lacrimal secretion and sialodochiectasias;
      that criteria for Sjogren's syndrome were fulfilled by 15 subjects in the RA
      group. The results of the study indicate that Sjogren's syndrome is to be
      regarded as part of the RA complex.

PMID- 20144095
TI  - Malignant synovioma.
AB  - Malignant synoviomas may clinically resemble localized arthritis and it is the
      rheumatologist who may be in a position to make the important early diagnosis.
      The course of the disease may be rapid or prolonged as illustrated by two case
      reports. The clinical, histological and roentgenological features are described
      and a review of the treatment and prognosis is given.

PMID- 20144096
TI  - Thermography in juvenile rheumatoid arthritis.
AB  - In the present investigation, thermography turned out to be a very useful tool
      for examination and follow-up study of child patients with rheumatoid arthritis.
      The series comprised 46 patients with juvenile rheumatoid arthritis (JRA) and 50
      non-rheumatic children of the same age groups.

PMID- 20144097
TI  - Observations on the symptoms and signs of "early" rheumatoid arthritis in a
      prospective study.
AB  - The authors have made a detailed study of 202 cases recognized as early RA. All
      of them were referred to the Institute for thorough examination and were
      afterwards followed up for two to six years. The observation of the course of the
      disease revealed four groups: 1. Cases where development of bone erosions proved
      the diagnosis of RA, 2. Cases in whom all previous symptoms and signs
      disappeared, 3. Cases in whom diagnosis could not be established after follow-up,
      4. Cases in whom other diseases were manifest. The first two groups were analysed
      retrospectively to find the characteristic features in the early stages of RA.

PMID- 20144098
TI  - The prevalence of rheumatoid arthritis in occupational groups.
AB  - Distributed on 66 large occupational groups the prevalence of classical,
      definite, probable and possible RA (according to ARA criteria) was determined in
      the general population. A total of 39, 418 persons were investigated in a sample
      survey of five geographical areas in Sweden-this being the total populations over
      the age of seven. The distance between the different areas is 150-650 km.
      Occupational groups with high prevalence of RA were: Males: Food and dairy
      workers, butchers, fishermen, agricultural workers, building foremen, machine and
      engine repairers, bakers, foremen, washers and ironers, textile workers, industry
      and factory workers. Females: Cleaning workers, doctors and nurses, nurse
      assistants, textile workers, shop assistants, bank, post and telegraph personnel
      and wives. From the present series it seems as if outdoor occupations with
      relatively heavy work have the highest prevalence of RA. Environmental factors
      apparently account for differences in prevalences of RA.

PMID- 20144099
TI  - On the presence of rheumatoid factor in joints before and after synovectomy.
AB  - The presence of rheumatoid factor in synovial fluid has been investigated before
      and after synovectomy. The sensitized sheep cell test (SSC) and acryl fixation
      test were used. Fourteen patients representing 18 knee joints in which
      synovectomy was performed, showed the same immunologic conditions in the synovial
      fluid before and after the surgical procedure. The relationship between the
      presence of immunoglobulins and certain structural features in the synovial
      tissue is discussed.

PMID- 20144100
TI  - Effects of osmium tetroxide on the rabbit knee joint normal synovial membrane.
AB  - The effect of osmium tetroxide, which is used in treatment of rheumatoid
      arthritis, was histologically and electronmicroscopically examined in the normal
      synovial membrane of the rabbit. The animals were albino rabbits, and they were
      20 altogether. 0.3 ml. of 1% OsO(4) solution was injected, i.a., in the right
      knee. The left knee joint served as a control. One minute after the injection,
      black reduced osmium was observed in the synovial membrane. The endothelial layer
      of the synovial membrane coagulated and disappeared within some days. Deep in the
      synovial membrane, a foreign body granuloma and a connective tissue scar appeared
      in five weeks. The result was a strong thickening of the synovial membrane.

PMID- 20144101
TI  - Pseudoxanthoma Elasticum (PXE) and Joint Manifestations.
AB  - A case of PXE is reported which, besides cardiac and gastrointestinal symptoms,
      also shows recurrent joint manifestations, possibly due to the basic disease.
      Histologically, the joint lesions resembled subacute synovitis to some extent.

PMID- 20144102
TI  - On the etiology of growth disturbance of the mandible in juvenile rheumatoid
      arthritis.
AB  - One case of congenital micrognathia unaccompanied by any other congenital
      malformations was discovered among 33, 000 school children surveyed. This case
      showed roentgenological evidence of condylar aplasia. The same change had been
      noted earlier in some cases of juvenile rheumatoid arthritis associated with
      micrognathia. The conclusion is drawn that in some of the children with RA
      associated with micrognathia, this latter has a congenital basis whereas, in
      other cases, it is due to affection of the temporomandibular joint.

PMID- 20144103
TI  - Studies on the possible presence of the uratebinding alpha-1-alpha-2 globulin in
      human erythrocytes.
AB  - Recent investigations indicate that urate is partly transported through the
      erythrocyte membrane by a process which might involve a protein-carrier system.
      In the present work erythrocyte proteins have therefore been studied with special
      emphasis on the possible presence of the urate-binding alpha-1-alpha-2 globulin.
      The erythrocytes were destroyed by freezing and thawing and the "ghosts"
      subsequently treated with desoxycholate or ultrasound. The three different
      protein fractions obtained were subjected to anion exchange chromatography on
      DEAE-Sephadex columns according to the procedure employed for isolating the urate
      binding alpha-1-alpha-2 globulin. In this way 10-14 different non-hemoglobin
      protein zones could be distinguished by vertical starch gel electrophoresis. None
      of these proteins, however, seemed to be identical to the urate-binding alpha-1
      alpha-2 globulin.

PMID- 20144104
TI  - Clearance of (125)i-labelled urographin from knee joints in rheumatoid arthritis.
AB  - (125)I-labelled Urographin has been used intra-articularly as tracer and 60 per
      cent Urographin as contrast in ten knee joints of patients with classical
      rheumatoid arthritis. Nine traumatic knees served as controls. The rapid rate of
      disappearance of the contrast from joints with rheumatoid inflammation was higher
      than in controls. Over the rheumatoid joints the radioactivity had decreased to
      half the initial value in 2.85 hrs. and over the traumatic joints in 3.70 hrs. In
      the radiographs clear evidence of absorption of contrast by the synovial
      membrane, the hyaline cartilage and the fibrocartilaginous tissue of the menisci
      was demonstrated. In one case visual proof was obtained of drainage of the
      contrast through the local lymphatics. The series of arthrograms taken from this
      knee indicate that this drainage was rapid.

PMID- 20144105
TI  - Reversible acute renal failure complicating rheumatoid arthritis.
AB  - Although morphological and functional kidney lesions are well known to occur in
      rheumatoid arthritis (RA), there appear to be no previous reports on reversible
      acute renal failure. That interstitial nephritis plays a part in acute renal
      failure is clinically documented but the pathophysiology is obscure. The role of
      raised interstitial pressure has often been discussed but convincing evidence is
      still lacking. Two patients with classical RA complicated by reversible oliguria
      and impaired kidney function are presented. Renal biopsies revealed no
      glomerular, tubular or amyloid lesions. The only light microscopic finding was
      greatly increased interstitial edema, which stained metachromatically with
      toluidine blue and was hyaluronidase-sensitive. It is supposed that the abnormal
      concentration of interstitial hyaluronic acid and its high water-binding capacity
      leads to an increase of interstitial pressure, which is followed by renal
      insufficiency. The mucinous edema of the kidneys is assumed to be an acute
      reaction of the pathological connective tissue in general.

PMID- 20144106
TI  - Annual meeting of the rheumatological association of sweden.

PMID- 20144107
TI  - The intestine and rheumatism.
AB  - Arthritis following certain Salmonella infections, dysentery, and nonspecific
      enterocolitis exemplifies the fact that intestinal infections can elicit
      rheumatic reactions. Recent observations indicate that in the last mentioned
      group specific microbes, such as Clostridium perfringens and Yersinia
      enterocolitica, may be involved. References are made to the findings of an
      abnormal intestinal flora, notably C. perfringens, in patients with chronic
      arthritis and of circulating and cell-bound antibodies to C. perfringens
      alphatoxin as evidence of an immunologic response to this microbe in rheumatoid
      disease.

PMID- 20144108
TI  - Sjogren's Syndrome Associated with Vitamin B(12) Deficiency.
AB  - Three patients showing Sjogren's syndrome in association with macrocytic anemia
      due to vitamin B(12) deficiency are described. Antibodies to parietal cells,
      intrinsic factor and salivary protein were investigated; positive test results
      were obtained in different combinations. Addisonian pernicious anemia as well as
      vitamin B(12)-malabsorption because of anti-intrinsic factor antibodies in
      gastric juice and/or malabsorption due to changes in the intestinal wall induced
      by Sjogren's syndrome are possible etiological factors. A case of Sjogren's
      syndrome associated with positive anti-parietal cell antibodies and
      histaminerefractory achylia is also reported. The concurrence of these two
      diseases known to be associated with autoimmune responses suggests the
      possibility of similar pathogenesis.

PMID- 20144109
TI  - Relationship of Systemic Lupus Erythematosus (SLE) to Rheumatoid Arthritis (RA),
      Discoid Lupus Erythematosus (DLE) and Sjogren's Syndrome: A Clinical Study.
AB  - In clinical and laboratory examinations carried out since 1954 we found the
      combination of SLE, RA, DLE and Sjogren's syndrome in 33% of 771 patients. In 61%
      of our 171 LE cell-positive cases there was classical RA which is a further proof
      of the close connection between these two diseases.

PMID- 20144110
TI  - Involvement of the lateral atlanto-axial joints as first and late symptom of
      rheumatoid arthritis.
AB  - Thirty cases of unilateral or bilateral atlanto-axial arthritis are described.
      They were found among 606 RA patients. According to the degree of involvement,
      the 30 cases were divided into four groups: A. 16 cases. B. 5 cases. C. 7 cases.
      D. 2 cases. In two patients the atlanto-axial arthritis was the primary lesion.
      The clinical and the radiological course of the disease is described. The
      systematic search for this type of arthritis is emphasized as it is often
      asymptomatic. The author gives details of a clinical test, specific for the
      function of the atlanto-axial joints.

PMID- 20144111
TI  - Inheritance of rheumatoid arthritis.
AB  - The inheritance of rheumatoid arthritis was investigated in three areas in Sweden
      where nearly the total population over the age of seven (22, 707 persons) was
      examined for the prevalence of rheumatoid arthritis (ARA-criteria). No
      significantly higher frequencies of rheumatoid arthritis were found among
      relatives of rheumatoid arthritics than among matched relatives of matched
      controls. The results are disappointing and throw no new light on possible
      inheritance of rheumatoid arthritis.

PMID- 20144112
TI  - Changes in the synovial fluid caused by osmic Acid.
AB  - 27 rheumatic patients with knee joint hydrops were studied for the effect of
      osmic acid on the synovial fluid. Special interest was taken in synovial
      leucocyte counts and electrophoretic patterns. A leucopenia preceded the
      leucocytosis in the synovial samples; both were thought to be induced by osmium.
      A precipitate formation from hyaluronate was thought to account for the
      leucopenia and this suggests a new hypothesis of osmic acid action. In the
      electrophoretic patterns there was a change in the electric charges of proteins.
      One week after osmic acid injection the pattern was normal.

PMID- 20144113
TI  - Muramidase (lysozyme) in joint fluid and serum of rheumatic patients.
AB  - The muramidase activity of serum was studied in 27 cases of rheumatoid arthritis.
      The enzyme activity in rheumatoid serum (mean 11.0 mug./ml.) did not differ
      significantly from that in the 30 healthy controls (mean 9.4 mug./ml.). The
      muramidase activity in the synovial fluid of 36 rheumatoid arthritis patients was
      markedly elevated (mean 20.2 mug./ml.). In osteoarthritic synovial fluid (8
      cases) the muramidase activity was low (mean 8.0 mug./ml.). No correlation was
      found between the total white blood count and the muramidase activity in
      rheumatoid synovial fluid. A positive relationship was observed between the
      enzyme activity and the total protein concentration. The elevated concentration
      of muramidase in synovial fluid of rheumatoid arthritis patients is interpreted
      as evidence of increased release of hydrolytic lysosomal enzymes. It remains to
      be shown which type of synovial fluid leukocytes produces the enzyme in question.

PMID- 20144114
TI  - Effect of Non-Steroidal Anti-Inflammatory Drugs on Osteoarthritis of the Knee:
      With Special Reference to PSP Clearance as an Indicator.
AB  - PSP clearance of the osteoarthritic knee was studied in 79 joints of 60 patients.
      Correlation between the clearance rate and the degree of disease activity (the
      grade of inflammatory exacerbation) was suggestive. Using PSP clearance, we
      studied the effect of non-steroidal anti-inflammatory drugs on the osteoarthritic
      knee. The results of this study are as follows: The drugs, phenylbutazone,
      indomethacin and acetyl-salicylic acid, are effective, when they are administered
      at the initial phase of inflammation, while in the chronic phase the effects of
      them are variable, though significant in patients whose PSP clearance rate is
      below 45 per cent. In the chronic and severely affected cases, the basic
      principles of therapy of osteoarthritic knees are avoidance of excessive use and
      the correct use of rest and physical therapy.

PMID- 20144115
TI  - Relationship Between IgG Complexes and ANTMgG Antibodies in Rheumatoid Arthritis.
AB  - A selective concentration of antibodies to IgG, both IgM and IgG rheumatoid
      factors and antibodies to the pepsin site of IgG, was demonstrated in eluates of
      rheumatoid tissues, but not in control tissues. Many eluates with high amounts of
      IgG complexes lacked free antibodies to IgG, even when these antibodies were
      present in the serum. This indicated blocking by IgG complexes. Thus IgM
      rheumatoid factor could evade detection in some "seronegative" patients by
      fixation to tissue IgG complexes.

PMID- 20144116
TI  - Collaboration Between Rheumatologist and Orthopedic Surgeon-a Necessity.
AB  - The importance of orthopedic surgery as an auxiliary to any treatment of
      rheumatoid arthritis is underlined in the present article. No treatment programme
      for rheumatoid arthritis is satisfactory, if it does not recognize this fact. It
      must form part of all future planning for hospital care of rheumatological
      patients.

PMID- 20144117
TI  - Dispersed cell cultures of rheumatoid synovial membrane.
AB  - The morphology of cells released from synovial tissues involved by rheumatoid
      arthritis and grown in tissue culture has been described. Cultures were well
      established and differentiated by the third day. In growth medium enriched with
      heat-inactivated rheumatoid serum syncytial cell masses frequently formed. This
      change particularly, was very like the characteristic cytopathic effect of a
      number of viruses.

PMID- 20144118
TI  - Technetium-99m in the study of rheumatic joints.
AB  - The accumulation of Tc-99m in knee and finger joints was studied in 41 rheumatic
      patients and 25 controls. The accumulation of the radioisotope was correlated
      with the intensity of active inflammation. Rheumatoid joints showed a stronger Tc
      99m uptake than joints with osteoarthritis. There was some overlap, however,
      which limits the value of the method. The effect of local and systemic anti
      rheumatic treatments could be followed with joint scanning. Radioactivity was
      also measured in the synovial fluid but this fraction of the Tc-99m was not
      large. The synovial fluid radioactivity tended to increase as the Tc-99m
      accumulation in the knee area decreased. Accumulation of Tc-99m in joints is
      regarded as principally due to the enhanced circulation in inflamed joint
      tissues.

PMID- 20144119
TI  - Electrodiagnostic investigation of the neuromuscular lesions in rheumatoid
      arthritis.
AB  - 85 muscles, in 30 rheumatoid arthritis patients, were examined by EMG. The
      patients were subdivided into steroid and non-steroid treated groups. In both
      groups, the EMG demonstrated myopathic, polymyositic and neuropathic lesions, the
      first two predominating. Similar changes were found regardless of the size of the
      muscle examined. A relatively high number of myopathic changes were observed in
      early RA. The activity of the disease did not seem to play an important role. No
      correlation with the condition of the adjacent joint was found. No patient had a
      normal EMG in all the muscles examined. The conduction velocity indicated an
      entrapment syndrome in four patients. Creatine phosphokinase was normal in 23
      patients, while aldolase was moderately high in 9 of 23 cases.

PMID- 20144120
TI  - The prevalence of rheumatoid arthritis in different geographical areas in sweden.
AB  - In the general population of 39,418 persons within areas in the counties of
      Norrbotten (BD), Jamtland (Z), Skaraborg (R), Kristianstad west coast (LV), and
      Kristianstad east coast (L) in Sweden all the inhabitants over the age of seven
      (in Norrbotten over the age of 14) were investigated for the total number of
      cases of rheumatoid arthritis. Re-investigations of non-response (10-20 %) were
      made. The southernmost and northernmost areas were about 1,500 km apart. Every
      person was examined naked or seminaked. The diagnostic criteria prepared by the
      American Rheumatism Association (ARA) were used. In the mathematical calculations
      it was possible to determine indices for correct comparisons of the prevalences
      in the different areas. The prevalence for RA (classical, definite probable,
      possible) in the populations examined was 3.1 per cent. The highest figures were
      observed in the southern part of the country (L, LV). The prevalences were higher
      in the coastal areas (in L, LV and BD) than in the inland areas (Z, R). The
      prevalence was higher in the non-response group than in the primarily
      investigated group.

PMID- 20144121
TI  - Alpha-mannosidase activity in synovial fluid.
AB  - A microassay technique for the evaluation of synovial fluid alpha-mannosidase
      activity is presented with the evaluation of 184 synovial fluid samples from a
      variety of arthropathic conditions. The results indicate a close correlation of
      enzyme activity with synovial fluid cell count and the degree of inflammation
      associated with the various types of joint disease. It is suggested that the
      evaluation of this and other lysosomal glycosidases offer a quantitative method
      for the evaluation of inflammatory joint disease.

PMID- 20144122
TI  - Scanning electron microscopic studies of extensor tendon degeneration in
      rheumatoid arthritis.
AB  - Examination of the surfaces of four normal and six rheumatoid tendons in the hand
      by scanning electron microscopy clearly showed the processes of degeneration
      affecting the tendons in rheumatoid arthritis. These findings seemed to
      correspond to the clinical state. The surfaces of the healthy tendons displayed
      fine networks of closely enmeshed collagen fibrils and parallel arrangements of
      collagen bundles. In acute rheumatoid tenosynovitis numerous inflammatory cells
      were found on the surfaces of the tendons, later crater and groove formations
      followed, as was observed in degenerated tendons and ruptured stumps in cases in
      which the active stage already had calmed down. The hypothesis is discussed that
      disorganization of tendons in rheumatoid disease may be caused by lysosomal
      enzymes present in greater concentration in the synovial fluid components of
      rheumatoid patients than in healthy subjects.

PMID- 20144123
TI  - Fibrin dissolution in synovial fluid.
AB  - Fibrinogen, fibrinogen-fibrin breakdown products (b.d.p.), fibrin stabilizing
      factor (FSF), plasminogen, alpha-2 macroglobulin and alpha-1 antitrypsin
      concentrations were estimated immunologically in normal and in pathological
      synovial fluids from patients with RA, gout, monoarthritis, rheumatic fever,
      osteoarthritis and traumatic arthritis. The fibrinolytic activity was determined
      by the fibrinplate method. Normal synovial fluid contained no fibrinogen, b.d.p.,
      FSF or alpha-2 macroglobulin, but traces of plasminogen and alpha-1 antitrypsin.
      By increasing inflammatory reactions increasing amounts of the various factors
      were demonstrable. No distinct, specific, patterns were found. Spontaneous
      fibrinolytic activity was demonstrable in the most exsudative cases, and in these
      high concentrations of fibrin breakdown products were present. These were also
      demonstrable in most pathological synovial fluids proving a recent proteolytic
      activity. It is suggested, that the fibrin breakdown products in pathological
      synovial fluids are partly resistent to proteolytic activity.

PMID- 20144124
TI  - A possible explanation for dizziness following SSRI discontinuation.
AB  - Dizziness is the most commonly reported symptom of abrupt discontinuation from
      the selective serotonin reuptake inhibitor (SSRI) category of antidepressants.
      The reported dizziness is exacerbated by even slight head movement, and therefore
      is likely to be vestibular in origin. The SSRIs most implicated are those with
      short half-lives and which are most selective for serotonin (as opposed to
      noradrenaline), e.g. paroxetine and sertraline. Since the vestibular nucleus
      complex (VNC) has an abundance of serotonin receptors, the abrupt withdrawal from
      an SSRI is likely to have a substantial impact on the electrophysiological
      activity of neurons within it. Here we suggest that the abrupt withdrawal from an
      SSRI is likely to cause a sudden decrease in serotonin in the VNC, which will
      disrupt the function of VNC neurons bilaterally, causing dizziness without
      vertigo.

PMID- 20144125
TI  - The Research Agenda for General Practice/Family Medicine and Primary Healthcare
      in Europe: a solid basis for innovative research.

PMID- 20144128
TI  - Cefepime and mortality: a real issue?
AB  - The fourth-generation cephalosporin, cefepime, has an antimicrobial spectrum that
      makes it a valuable antibiotic for empirical treatment of neutropenic fever.
      Randomized trials have proven the efficacy and safety of cefepime in neutropenic
      fever. However, 2 recent meta-analyses have shown an increased all-cause
      mortality for cefepime. Since then, many clinicians have been left in doubt about
      the use of cefepime for this indication. In this paper, we put in perspective
      some of the methodological and clinical issues and call for further clinical
      analyses.

PMID- 20144129
TI  - Comparative virulence of three species of Exophiala in mice.
AB  - The virulence of Exophiala dermatitidis, E. oligosperma and E. xenobiotica, three
      of the most common members of the genus that cause human infections, was
      evaluated using experimental models of disseminated infection in
      immunocompromised mice. Exophiala dermatitidis, and to a lesser extent E.
      oligosperma, were the two species causing the highest mortality, while mice
      infected with E. xenobiotica had the lowest mortality. Tissue burden and
      histopathology studies demonstrated the neurotropism of E. dermatitidis, while E.
      oligosperma and E. xenobiotica had a limited capacity for invading brain tissue.
      These models could be useful for testing new therapies against Exophiala
      infections.

PMID- 20144130
TI  - Esophagitis caused by Candida guilliermondii in diabetes mellitus: first reported
      case.
AB  - Diabetic patients are at risk of acquiring esophageal infections such as those
      caused by members of the genus Candida. Here we describe a case in which Candida
      guilliermondii was isolated from the esophageal mucosa of a patient with
      uncontrolled diabetes mellitus. Due to inappropriate and inaccurate
      identification, the emergence of non-C. albicans Candida species as potential
      pathogens has been underestimated. This should be a cause of concern since C.
      guilliermondii is a normal component of human microbiota. The identity of the
      isolate in our case was confirmed by its characteristic morphophysiological
      features and amplification of rDNA using species-specific primers. Fluconazole
      therapy produced no improvement of the esophageal symptoms, and resistance of the
      etiologic agent was confirmed through in vitro susceptibility tests. This is
      thought to be the first documented case of C. guilliermondii esophagitis in a
      patient with diabetes mellitus.

PMID- 20144131
TI  - Evaluation of the Etest method for susceptibility testing of Aspergillus spp. and
      Fusarium spp. to three echinocandins.
AB  - We performed Etest and broth microdilution (BMD) susceptibility testing of
      caspofungin, micafungin and anidulafungin against 67 clinical isolates of
      Aspergillus spp. and 10 Fusarium spp. Minimal effective concentrations (MECs) by
      BMD were read after 24 h of incubation at 35 degrees C and Etest MICs were read
      at 24 and 48 h. MECs < or =0.25 mg/l were obtained with caspofungin for all
      Aspergillus spp. tested but Etest MICs were < or =1 mg/l at 24 h. The agreement
      between caspofungin Etest and broth microdilution was good for all Aspergillus
      species tested (range 82.4-100%) except for A. niger and A. glaucus at 24 h of
      incubation. Micafungin and anidulafungin MEC and MIC results were lower than
      those of caspofungin (< or =0.015 mg/l) at 24 and 48 h for all Aspergillus
      tested. The agreement between the methods was excellent (100%) for micafungin and
      anidulafungin for all Aspergillus species tested. The three echinocandins were
      inactive against all isolates of Fusarium spp. showing MECs and MICs >8 mg/l. The
      Etest method could be a suitable procedure to test the susceptibility of most
      Aspergillus species to caspofungin, micafungin and anidulafungin; the best
      agreement was at 24 h.

PMID- 20144133
TI  - A retrospective analysis of toxicity studies in dogs and impact on the chronic
      reference dose for conventional pesticide chemicals.
AB  - Prior to October 2007, the US Environmental Protection Agency (EPA) required both
      13-week and 1-year studies in Beagle dogs be submitted in support of registration
      for pesticides. Following an extensive retrospective analysis, we (the authors)
      determined that the 1-year toxicity dog study should be eliminated as a
      requirement for pesticide registration. The present work presents this
      retrospective analysis of results from 13-week and 1-year dog studies for 110
      conventional pesticide chemicals, representing more than 50 classes of
      pesticides. The data were evaluated to determine if the 13-week dog study, in
      addition to the long-term studies in two rodent species (mice and rats), were
      sufficient for the identification of no observed adverse effect levels (NOAELs)
      and lowest observed adverse effect levels (LOAELs) for the derivation of chronic
      reference doses (RfD). Only pesticides with adequate 13-week and 1-year duration
      studies were included in the present evaluation. Toxicity endpoints and dose
      response data from 13-week and 1-year studies were compared. The analysis showed
      that 70 of the 110 pesticides had similar critical effects regardless of duration
      and had NOAELs and LOAELs within a difference of 1.5-fold of each other. For the
      remaining 40 pesticides, 31 had lower NOAELs and LOAELs in the 1-year study,
      primarily due to dose selection and spacing. In only 2% of the cases were
      additional toxic effects identified in the 1-year study that were not observed in
      the 13-week study and/or in the rodent studies. In 8% of the cases, the 1-year
      dog had a lower NOAEL and/or LOAEL than the 13-week study, but there would have
      been no regulatory impact if the 1-year dog study had not been performed because
      adequate data were available from the other required studies. A dog toxicity
      study beyond 13-weeks does not have significant impact on the derivation of a
      chronic RfD for pesticide risk assessment.

PMID- 20144134
TI  - A retrospective analysis of Acute Reference Doses for pesticides evaluated in the
      European Union.
AB  - This retrospective analysis of Acute Reference Doses (ARfD) values is based on
      pesticides that have been evaluated and peer-reviewed in Europe between 2000 and
      2008. The published database of the 198 ARfDs was analysed. For 48% of all
      substances, no ARfD was considered necessary because of the low acute toxicity of
      these pesticides. The majority of ARfDs were based on studies that were required
      for pesticides and conducted for regulatory purposes and in which specific acute
      alerts were investigated. In less than 10% of cases, conservatively established
      ARfDs were based on repeated-dose toxicity or multigeneration studies. For 4 of
      these 198 pesticides, a refinement of a conservative ARfD using an additional
      toxicity study would be justifiable because a more realistic calculation of the
      exposure component was not sufficient to eliminate any health concern. In the
      analysed database, special studies for ARfD refinement were submitted for 8 of
      the 198 pesticides. They were mostly performed in addition to the basic acute
      toxicity data requirements, in cases in which it was apparent that the acute
      intake estimation exceeded a conservatively established ARfD. However, several
      studies were not accepted by regulatory authorities because of quality
      deficiencies. The results of this analysis indicate that the development of a
      harmonised study design that produces consistent and robust toxicological data on
      the occurrence of acute effects and their dose response would be valuable for
      setting ARfDs. Such a protocol, plus additional research on the mode of action
      for acute effects observed in relevant targets for ARfD derivation, is considered
      as an important prerequisite for an improved acute risk assessment for
      pesticides.

PMID- 20144135
TI  - The mouse carcinogenicity study is no longer a scientifically justifiable core
      data requirement for the safety assessment of pesticides.
AB  - Regulatory tests investigating pesticide carcinogenicity potential routinely
      comprise a battery of in vitro and in vivo genotoxicity studies and two cancer
      bioassays, one in rats and one in mice. The genotoxicity testing strategy
      essentially ensures that genotoxic compounds are eliminated, and any carcinogens
      identified in subsequent lifetime studies are probably nongenotoxic in character.
      Assessment of 202 pesticide evaluations from the European Union review programme
      under Directive 91/414/EEC indicated that the mouse carcinogenicity study
      contributed little or nothing to either derivation of an acceptable daily intake
      (ADI) for assessment of chronic risk to humans, or hazard classification for
      labelling purposes. From a pesticide approval perspective, the mouse study did
      not influence a single outcome. From a risk assessment perspective, the ADI for
      just one pesticide was based on tumours in mice and this would have barely
      changed if the mouse data had not been available. In total, only 10 (5%)
      pesticide ADIs were based solely on the mouse carcinogenicity study and even in
      these few cases, a similar value would have been identified from other studies if
      the mouse study had not been available. For pesticides with treatment-related
      tumours only in mice, just three, or 1.5%, were classified as carcinogens and all
      were in the lowest category, Category 3 (R40). For pesticides with treatment
      related tumours in mice and rats, the mouse data were probably the main, if not
      the only, cause for another three cases of R40 classification. Absence of the
      mouse studies would not have influenced assignment of the higher, Category 2
      (R45), cancer classification for any substance with treatment-related tumours in
      both species as all decisions for these substances were limited to Category 3 or
      'unclassified' outcomes. Over 100,000 mice were used to test these pesticides.
      This review shows that the mouse carcinogenicity studies did not provide
      significant information over and above that provided by the rat studies, and
      underpins the opportunity, from both a scientific and an animal welfare
      perspective, to remove the mouse carcinogenicity study from regulatory data
      requirements for the testing of pesticides.

PMID- 20144136
TI  - Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and
      use alternative approaches.
AB  - Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin
      and eye irritancy, and skin sensitisation potential of chemicals is required
      under regulatory schemes worldwide. In vivo studies conducted to assess these
      endpoints can sometimes be associated with substantial adverse effects in the
      test animals, and their use should always be scientifically justified. It has
      been argued that while information obtained from such acute tests provides data
      needed to meet classification and labelling regulations, it is of limited value
      for hazard and risk assessments. Inconsistent application of in vitro
      replacements, protocol requirements across regions, and bridging principles also
      contribute to unnecessary and redundant animal testing. Assessment of data from
      acute oral and dermal toxicity testing demonstrates that acute dermal testing
      rarely provides value for hazard assessment purposes when an acute oral study has
      been conducted. Options to waive requirements for acute oral and inhalation
      toxicity testing should be employed to avoid unnecessary in vivo studies. In
      vitro irritation models should receive wider adoption and be used to meet
      regulatory needs. Global requirements for sensitisation testing need continued
      harmonisation for both substance and mixture assessments. This paper highlights
      where alternative approaches or elimination of tests can reduce and refine animal
      use for acute toxicity requirements.

PMID- 20144137
TI  - Evaluation of varenicline as an aid to smoking cessation in UK general practice -
      a THIN database study.
AB  - OBJECTIVES: Varenicline is a licensed smoking cessation medication in the EU, USA
      and many other countries worldwide. This study was designed to assess its
      effectiveness in a UK general practice setting. METHODS: The main outcome measure
      was the rate of smoking cessation, defined as the seven-day point prevalence
      after six months from starting varenicline. Varenicline users were identified
      from records in The Health Improvement Network (THIN) database. A questionnaire
      on smoking cessation was sent to patients who commenced treatment close to the
      selection date (six months prior to the date of questionnaire dispatch). RESULTS:
      The response rate was 26.4%: 193 responses were received. Ninety percent had
      previously attempted to stop smoking and 87.4% had used nicotine replacement
      therapy during the previous attempt to stop smoking. The overall smoking
      cessation rate was 49.5%. There was a strong association between the duration of
      varenicline treatment and smoking cessation. Patients who reported using
      varenicline for 9-12 weeks were 11 times more likely to stop smoking than those
      who completed less than two weeks of treatment. There was some evidence that
      patients with a longer history of smoking were less likely to stop. No
      association was observed between smoking cessation and: previous number of
      cigarettes smoked per day; number of previous attempts to stop smoking; or
      motivations for stopping. CONCLUSIONS: Varenicline appeared to be a useful
      pharmacological aid to smoking cessation in a general practice setting. The
      observed effectiveness was similar to the efficacy estimates from previously
      reported clinical trials. However, the response rate was lower than expected and
      responders tended to be older, more likely to suffer from chronic obstructive
      pulmonary disease and to live in more affluent areas than non-responders.
      Responses were self-reported and not clinically validated therefore recall bias
      may be an issue.

PMID- 20144138
TI  - Telmisartan and hydrochlorothiazide combination therapy for the treatment of
      hypertension.
AB  - BACKGROUND: Control of elevated blood pressure has been shown to reduce the risk
      of cardiovascular events. The angiotensin II receptor blocker (ARB), telmisartan,
      has been shown to provide effective 24-hour blood pressure control. Additional
      antihypertensive efficacy can be achieved by combining telmisartan with the
      thiazide diuretic hydrochlorothiazide (HCTZ). OBJECTIVE: To review the clinical
      data in combination therapy with telmisartan and HCTZ. METHODS: Search of Medline
      and Embase for published clinical studies using the keywords telmisartan and
      HCTZ. FINDINGS: The telmisartan/HCTZ combination provides significant reductions
      in blood pressure, effective 24-hour blood pressure control and is well
      tolerated. Blood pressure reductions with this combination are greater than those
      achieved with either drug alone, and in comparative studies telmisartan/HCTZ is
      more effective than other ARB/HCTZ combinations. However, it should be noted that
      some of the combinations assessed used doses of the drugs that were commercially
      available at the time of the trial and not higher doses that have been shown to
      have greater antihypertensive efficacy. CONCLUSION: The combination of
      telmisartan/HCTZ is an effective and well-tolerated treatment option for patients
      with hypertension.

PMID- 20144139
TI  - Challenges of therapeutic substitution of drugs for economic reasons: focus on
      CVD prevention.
AB  - BACKGROUND: Healthcare systems throughout the world are under increasing pressure
      to control and minimise costs. The substitution of initially-prescribed drugs
      with cheaper equivalents is an obvious option which presents a rapid and visible
      means to reduce these costs. Whether the substitution improves patient and/or
      population outcomes must be appraised and this paper highlights the conditions
      under which therapeutic substitution may require additional thought and
      consideration. SCOPE: In this paper, some of the medical evidence and the
      regulatory environment for and against the three types of therapeutic
      substitution - generic, within-class and between-class - are discussed. This
      article is not an exhaustive review of the literature, but captures some of the
      key clinical, pharmacological, economic, policy and ethical issues regarding
      generic and therapeutic substitution. Search criteria of the most commonly used
      terms, i.e. therapeutic substitution, switching, interchange, and bioequivalence,
      were applied to Embase, PubMed and Google Scholar to identify relevant
      publications. FINDINGS: Although population studies support therapeutic
      substitution in principle, there is evidence that substitution may not always
      result in therapeutic equivalence in individual patients, with the consequent
      potential for greater risks of decreased efficacy and/or increased safety
      concerns. Factors such as patient choice and therapeutic equivalence also play an
      important role in the effectiveness of the treatment and overall management of
      the patient. The pan-European regulatory environment provides another
      contradiction, encouraging widespread cost containment through reduction in drug
      acquisition costs, while simultaneously promoting an increased role for patients
      in defining and managing their own treatment. CONCLUSIONS: There is a strong
      rationale for careful management in some patients with cardiovascular disease.
      Treatment decisions should be transparent and based on strong clinical evidence.
      If not, drug substitution on economic grounds alone cannot be considered to be in
      the individual patient's interest and is therefore unethical.

PMID- 20144140
TI  - Unifying mechanism for metals in toxicity, carcinogenicity and therapeutic
      action: integrated approach involving electron transfer, oxidative stress,
      antioxidants, cell signaling and receptors.
AB  - This comprehensive review of biometals involves the unifying theme of electron
      transfer, reactive oxygen species, and oxidative stress (OS) applied to toxicity,
      carcinogenicity, and therapeutic action. The beneficial effect of antioxidants
      supports the participation of OS. The metals involved are mainly in the heavier
      category. An important aspect is the favorable reduction potential exhibited by
      the bioactive materials that permits redox cycling in vivo with the generation of
      oxy radicals. The basic mechanistic theme is applicable to other electron
      transfer (ET) functionalities. Appreciable evidence indicates the participation
      of cell signaling in various ways. Also, a simplifying framework is provided
      based on radical species and electrochemistry (ET and molecular electrostatic
      potential). This review also discusses receptor participation with focus on
      binding to proteins. Resultant physiological effects are summarized. The overview
      provides an integrated approach to metal bioactivation.

PMID- 20144143
TI  - Rice pads: novel devices for homogeneous fat suppression in the knee.
AB  - BACKGROUND: In magnetic resonance imaging (MRI) of the knee joint, when imaging
      the knee in a flexed position using the chemical-shift-selective (CHESS) method,
      lingering fat signals in the popliteal region are sometimes seen. PURPOSE: To
      investigate whether a pad filled with rice (rice pad) placed in the popliteal
      space is effective in eliminating the lingering fat signals in MR images of the
      flexed knee, based on the hypothesis that the use of a rice pad would improve the
      fat suppression effect. MATERIAL AND METHODS: Subjects were 10 healthy volunteers
      (five males, five females; age, 20-45 years) from whom images were taken using
      CHESS. Images were obtained with: 1) the knee extended and nothing placed
      underneath; 2) the knee bent with a sponge placed underneath; and 3) the knee
      bent with a rice pad placed underneath. The effectiveness of suppressing fat
      signals was visually assessed by one radiologist and one radiological
      technologist. RESULTS: The fat suppression effect in images obtained with the
      knee extended was good. In contrast, the images made with a sponge under the knee
      had conspicuous lingering fat signals for nearly all subjects. In the images made
      with a rice pad under the knee, a uniformly good fat signal suppression effect
      was seen in all patients, and the assessment score was far higher than that with
      the sponge pillow (P<0.001). CONCLUSION: Lingering fat signals were suppressed
      with the use of a rice pad, and fat-suppressed images of the knee joint using
      CHESS were found to be improved.

PMID- 20144144
TI  - Relief of radicular pain in metastatic disease by vertebroplasty.
AB  - Two patients with compression fractures from metastases who had pain with
      radicular symptoms mainly in upright position that resolved when not upright and
      were treated with vertebroplasty were retrospectively analyzed. Both patients had
      symptom relief at treated levels until death. These cases show that patients with
      radicular signs and symptoms from compression fractures secondary to metastases
      or myeloma, worse in upright position and relieved when recumbent, may benefit
      from vertebroplasty.

PMID- 20144145
TI  - Assessment of hip dysplasia and osteoarthritis: variability of different methods.
AB  - BACKGROUND: Reliable assessment of hip dysplasia and osteoarthritis is crucial in
      young adults who may benefit from joint-preserving surgery. PURPOSE: To
      investigate the variability of different methods for diagnostic assessment of hip
      dysplasia and osteoarthritis. MATERIAL AND METHODS: By each of four observers,
      two assessments were done by vision and two by angle construction. For both
      methods, the intra- and interobserver variability of center-edge and acetabular
      index angle assessment were analyzed. The observers' ability to diagnose hip
      dysplasia and osteoarthritis were assessed. All measures were compared to those
      made on computed tomography scan. RESULTS: Intra- and interobserver variability
      of angle assessment was less when angles were drawn compared with assessment by
      vision, and the observers' ability to diagnose hip dysplasia improved when angles
      were drawn. Assessment of osteoarthritis in general showed poor agreement with
      findings on computed tomography scan. CONCLUSION: We recommend that angles always
      should be drawn for assessment of hip dysplasia on pelvic radiographs. Given the
      inherent variability of diagnostic assessment of hip dysplasia, a computed
      tomography scan could be considered in patients with relevant hip symptoms and a
      center-edge angle between 20 degrees and 30 degrees . Osteoarthritis should be
      assessed by measuring the joint space width or by classifying the Tonnis grade as
      either 0-1 or 2-3.

PMID- 20144146
TI  - Role of three-dimensional fluid-attenuated inversion recovery (3D FLAIR) and
      proton density magnetic resonance imaging for the detection and evaluation of
      lesion extent of focal cortical dysplasia in patients with refractory epilepsy.
AB  - BACKGROUND: Focal cortical dysplasia (FCD) is often associated with epilepsy.
      Identification of FCD can be difficult due to subtle magnetic resonance imaging
      (MRI) changes. Though fluid-attenuated inversion recovery (FLAIR) sequence
      detects the majority of these lesions, smaller lesions may go unnoticed while
      larger lesions may be poorly delineated. PURPOSE: To determine the ability of a
      specialized epilepsy protocol in visualizing and delineating the extent of FCD.
      MATERIAL AND METHODS: We compared the imaging findings in nine patients with
      cortical malformation who underwent routine epilepsy MR imaging as well as a
      specialized epilepsy protocol. All imaging was done on a 1.5T MR unit. The
      specialized epilepsy protocol included 3D FLAIR in the sagittal plane as well as
      proton density (PD) and high-resolution T2-weighted (T2W) images in the
      transverse plane. RESULTS: In all nine patients, the specialized protocol
      identified lesion anatomy better. In three patients in whom routine MRI was
      normal, the specialized epilepsy protocol including 3D FLAIR helped in
      identifying the lesions. One of these patients underwent surgery, and histo
      pathology revealed a cortical dysplasia. In one patient, lesion characterization
      was improved, while in the remaining patients the extent of the FCD was more
      clearly demonstrated in the 3D FLAIR and PD images. Statistical analysis of
      images for cortical thickness, cortical signal intensity, adjacent white matter
      abnormalities, and gray-white matter junction showed significant statistical
      difference in the ability of 3D FLAIR to assess these aspects over conventional
      images. PD images were also found superior to the routine epilepsy protocol in
      assessment of cortical signal, adjacent white matter, and gray-white matter
      junction. CONCLUSION: Specialized MRI sequences and techniques should be
      performed whenever there is a high suspicion of cortical dysplasia, especially
      when they remain occult on conventional MR protocols. These techniques can also
      be used to define lesion extent more precisely.

PMID- 20144147
TI  - Correlation between lactate and neuronal cell damage in the rat brain after focal
      ischemia: An in vivo 1H magnetic resonance spectroscopic (1H-MRS) study.
AB  - BACKGROUND: Increased levels of lactate are observed by (1)H magnetic resonance
      spectroscopy ((1)H-MRS) in rat brains after stroke. However, it is not known
      whether the changes in lactate levels are predictive of the degree of neuronal
      damage. PURPOSE: To investigate the correlation between changes in lactate and
      lipid levels measured by (1)H-MRS and neuronal cell damage in the rat brain.
      MATERIAL AND METHODS: A middle cerebral artery occlusion (MCAO) model was used to
      evaluate focal ischemia in rats (n=36). After MCAO for 90 min T2-weighted images
      (T2WIs), diffusion-weighted images (DWIs), and (1)H-MRS data were obtained from
      brains immediately, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, 3 days, and 7
      days after reperfusion. Infarct volumes were measured in T2WIs obtained 4 weeks
      after reperfusion. The degree of neuronal damage was measured by terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      (TUNEL) staining in three rats from each group at the same time as brain images
      were collected. RESULTS: Creatine (Cr)-normalized lactate + lipid levels
      ([Lac+Lip]/Cr) were negatively correlated with Cr-normalized N-acetyl-L-aspartate
      levels (NAA/Cr) and positively correlated with TUNEL-positive cell numbers up to
      24 hours after reperfusion. (Lac+Lip)/Cr at 6 hours and 9 hours was significantly
      correlated with NAA/Cr at 7 days, but there was no significant correlation
      between (Lac+Lip)/Cr during the first 24 hours and infarct volume at 4 weeks.
      CONCLUSION: Up to 24 hours after reperfusion, (Lac+Lip)/Cr was strongly
      negatively correlated with NAA/Cr, and was a good predictor of neuronal damage at
      7 days; however, it was not predictive of final infarct volume at 4 weeks.

PMID- 20144149
TI  - MMP28 gene expression is regulated by Sp1 transcription factor acetylation.
AB  - MMP-28 (epilysin) is a recently cloned member of the MMP (matrix
      metalloproteinase) family. It is highly expressed in the skin by keratinocytes,
      the developing and regenerating nervous system and a number of other normal human
      tissues, as well as a number of carcinomas. The MMP28 promoter has previously
      been cloned and characterized identifying a conserved GT-box that binds Sp1/Sp3
      (specificity proteins 1 and 3) proteins and is essential for the basal expression
      of the gene. The present study demonstrates that MMP28 expression is induced by
      HDAC (histone deacetylase) inhibitors and that this effect is mediated through
      the GT-box. Transient transfection assays have shown that the induction of MMP28
      expression by the HDAC inhibitior TSA (trichostatin A) is mediated via Sp1 at the
      GT-box. Immunoprecipitation experiments have shown that the acetylation of Sp1
      and Sp3 is increased by TSA treatment; however, no effect on DNA binding was
      observed. Histone acetyltransferases such as p300 and P/CAF [p300/CREB (cAMP
      response-element-binding protein)-binding protein-associated factor] increased
      induction of the MMP28 promoter by Sp1. Knockdown of HDAC1 using siRNA (small
      interfering RNA) also induces the MMP28 promoter. Oligonucleotide pulldown
      identified STRAP (serine/threonine kinase receptor-associated protein) as a
      further protein recruited to the MMP28 promoter and acting functionally with Sp1.

PMID- 20144148
TI  - Electron capture dissociation mass spectrometric analysis of lysine
      phosphorylated peptides.
AB  - Phosphorylation of proteins is an essential signalling mechanism in eukaryotic
      and prokaryotic cells. Although N-phosphorylation of basic amino acid is known
      for its importance in biological systems, it is still poorly explored in terms of
      products and mechanisms. In the present study, two MS fragmentation methods, ECD
      (electron-capture dissociation) and CID (collision-induced dissociation), were
      tested as tools for analysis of N-phosphorylation of three model peptides,
      RKRSRAE, RKRARKE and PLSRTLSVAAKK. The peptides were phosphorylated by reaction
      with monopotassium phosphoramidate. The results were confirmed by 1H NMR and 31P
      NMR studies. The ECD method was found useful for the localization of
      phosphorylation sites in unstable lysine-phosphorylated peptides. Its main
      advantage is a significant reduction of the neutral losses related to the
      phosphoramidate moiety. Moreover, the results indicate that the ECD-MS may be
      useful for analysis of regioselectivity of the N-phosphorylation reaction.
      Stabilities of the obtained lysine-phosphorylated peptides under various
      conditions were also tested.

PMID- 20144151
TI  - [Morphology of acute myocardial infarction at prenecrotic stage].
AB  - We studied morphological changes of myocardium and content of glucose, potassium,
      calcium, sodium in pericardial fluid in persons who died suddenly of myocardial
      infarction at its prenecrotic stage at prehospital phase. It was established that
      acute myocardial infarction at prenecrotic stage can run in 2 morphological forms
      - either with transmural or with subendo- or epicardial localization of ischemic
      process in left ventricular wall. Transmural injury is characterized by large
      volume of ischemic damage of the left ventricle, generalized spasm of arterial
      system of the heart, changes of cardiomyocytes with derangement of their energy
      metabolism and contractile capacity. In subendo- or epicardial localization foci
      of ischemic injury alternated with areas of normal blood supply. Similar
      character of disturbances of rheological properties of blood with thrombosis of
      microcirculatory bed and of number of markers of ventricular fibrillation between
      these two forms create preconditions for increase of the zone of necrosis in
      myocardium and cause high risk of development of rhythm disorders.

PMID- 20144150
TI  - Electrostatic interactions play a minor role in the binding of ExoS to 14-3-3
      proteins.
AB  - 14-3-3 proteins belong to a family of conserved molecules expressed in all
      eukaryotic cells that play an important role in a multitude of signalling
      pathways. 14-3-3 proteins bind either to phosphoserine/phosphothreonine residues
      or to sequence-specific non-phosphorylated motifs in more than 200 interaction
      partners [Pozuelo Rubio, Geraghty, Wong, Wood, Campbell, Morrice and Mackintosh
      (2004) Biochem. J. 379, 395-408]. These interactions result in cell-cycle
      regulation, apoptosis, stress responses, cell metabolism and malignant
      transformation. One example of a phosphorylation-independent interaction is the
      binding of 14-3-3 to ExoS (exoenzyme S), a bacterial ADP-ribosyltransferase toxin
      of Pseudomonas aeruginosa. In the present study, we have utilized additional
      biochemical and infection analyses to define further the structural basis of the
      interaction between ExoS and 14-3-3. An ExoS leucine-substitution mutant
      dramatically reduced the interaction potential with 14-3-3 suggesting that
      Leu422, Leu423, Leu426 and Leu428 of ExoS are important for its interaction with
      14-3-3, its enzymatic activity and cytotoxicity. However, ExoS substitution
      mutants of residues that interact with 14-3-3 through an electrostatic
      interaction, such as Ser416, His418, Asp424 and Asp427, showed no reduction in
      their interaction potential with 14-3-3. These ExoS substitution mutants were
      also as aggressive as wild-type ExoS at inducing cell death and to modify
      endogenous ExoS target within the cell. In conclusion, electrostatic interaction
      between ExoS and 14-3-3 via polar residues (Ser416, His418, Asp424 and Asp427)
      appears to be of secondary importance. Thus the interaction between the 'roof' of
      the groove of 14-3-3 and ExoS relies more on hydrophobic interaction forces,
      which probably contributes to induce cell death after ExoS infection and
      activation.

PMID- 20144152
TI  - [Myocardial hypertrophy in patients with hypertensive disease: the role of
      genetic polymorphism of beta-adrenoreactive structures].
AB  - Aim of the study was investigation of association of polymorphic markers
      Gly389Arg and Ser49Gly of ADRB1 gene, Gly1l6Arg and Glu27Gln of ADRB2 gene,
      Trp64Arg of ADRB3 gene, and 825 of GNB3 gene with structural and functional
      peculiarities of the left ventricular (LV) myocardium in patients with
      hypertensive disease. We examined 177 patients - 83 (46.9%) men and 94 (53.1%)
      women. Mean age was 60.6 +/- 0.76 years. In the studied group there were 19
      patients (10.9%) with I degree arterial hypertension (AH), 57 patients (32.8%)
      with II degree AH, and 101 patients (56.3%) with III degree AH. Structural
      peculiarities of LV myocardium were investigated with the help of
      echocardiography. There turned out to be 40 patients without signs of LV
      hypertrophy and 137 patients with increase of LV myocardial mass index. patients
      with LV hypertrophy had higher frequency of genotype Arg/Arg of polymorphic maker
      Gly398Arg of ADRB1 gene (=0.008. OR 2.32 [CI 1.34 - 4.11]). In patients with
      concentric and eccentric hypertrophy significantly higher frequency of Arg/Arg
      genotype compared with patients with normal LV geometry and concentric LV
      remodeling was also noted. At conduction of multifactorial analysis independently
      connected with increase of LV myocardial mass turned out age of patients, level
      of systolic arterial pressure, presence of excessive body mass and carriage of
      Arg/Arg genotype of polymorphic marker Gly389Arg of ADRB1 gene.

PMID- 20144153
TI  - [Evaluation of long-term therapy influence with angiotensin converting enzyme
      inhibitor lisinopril on morphofunctional parameters of the left ventricle,
      peripheral artery endothelium disfunction and painless myocardial ischemia in
      premenopausal women with hypertension].
AB  - Aim of the study was to assess influence of long-term therapy with angiotensin
      converting enzyme inhibitor lisinopril on morphofunctional parameters of the left
      ventricle (LV) and painless myocardial ischemia in 109 premenopausal women with
      stage II hypertension depending on functional state of peripheral artery
      endothelium. The results show that lisinopril therapy in premenopausal women with
      hypertension can stop or even cause regression of LV myocardial hypertrophy and
      produce favorable effect on LV remodeling mostly in women with concentric type of
      hypertrophy and/or without endothelial dysfunction, and has positive effect on
      frequency of painless myocardial ischemia events.

PMID- 20144154
TI  - [Comparison of transthoracic, transesophageal, and intracardiac echocardiography
      sensitivity for guiding transseptal puncture during radiofrequency ablation in
      the left atrium].
AB  - The paper contains comparison of sensitivity and rates of false negative results
      of transthoracic (TT), transesophageal (TE), and intracardiac (IC)
      echocardiography (echoCG) during transseptal puncture in the run of the procedure
      of radiofrequency ablation of atrial fibrillation. In the work fulfilled we
      analyzed results of 208 echocardiographical intraprocedural investigations
      conducted with the aim of visualization of interatrial septum (IAS) during
      transseptal puncture. TT, TE and IC echoCG were carried out in 32, 26, and 150
      cases, respectively. Phenomenon of IAS stretching was visualized by TT echoCG in
      2 (6%) cases (sensitivity 6.7%). At TE tenting phenomenon was verified in 20
      patients (20%) (sensitivity 86.9%). Puncture of IAS was carried out under IC
      echoCG control in 127 patients. Puncture was made in the center of thin portion
      of IAS (in the region of fossa ovalis), in its upper and lower portions in 65,
      28, and 15.7% of cases, respectively. Sensitivity of IC echoCG was 98.4%. Rate of
      false positive results reached 92.8, 13.04 and 1.5% for TT, TE and IC echoCG,
      respectively. At present IC echoCG is most sensitive and safe ultrasound
      technique for verification of optimal positioning of the system for conduct of
      transseptal puncture in the region of IAS in comparison with TT and TE echoCG.

PMID- 20144155
TI  - [The study of heart rhythm variability during stress testing].
AB  - Individual heart rhythm variability is determined on the basis of mathematical
      models of changeability of cardiointervals during stress and function of their
      distribution. We has revealed its dependence on tolerability to physical effort
      (degree of training, endurance). We also established diagnostic and prognostic
      value of extremums of distribution of lengths of intervals between cardiocycles
      (duration of R-R intervals).

PMID- 20144156
TI  - [Stromal progenitor cells and blood leukocytes after implantation of drug-eluting
      stents].
AB  - Aim of the study was to assess participation in development of restenosis of
      circulating in blood progenitor cells of stromal line of differentiation and
      polymorphonuclear granulocytes. We compared levels of osteonectin positive
      progenitor cells, neutrophils, eosinophils, and basophils in blood of patients
      with ischemic heart disease (IHD) in whom according to data of angiographic study
      after endovascular myocardial revascularization with the help of stents with drug
      coating (Cypher, Cordis Corp, USA) restenosis was detected (n=15), in patients
      without restenosis (n=23), and in healthy persons (n=17). Levels of stromal
      progenitor cells and polymorphonuclear granulocytes in blood were measured with
      the help of methods of flow cytometry. In groups of patients with IHD with and
      without restenosis number of osteonectin positive cells in blood was higher than
      in healthy subjects (2.4+/-0.7 and 2.5+/-0.9 vs 1.5+/-0.5 cells/ microL,
      respectively, p=0.004) without significant differences between groups (p=0.59).
      These 2 groups of patients did not differ by numbers of leukocytes, neutrophils,
      and basophils in blood. At the same time we found that in patients with
      restenosis number of eosinophils in blood was significantly greater than in the
      group of patients without restenosis (262+/-68 vs 124+/-67 cells/ microL,
      respectively p<0.001). Moreover in patients with level of eosinophils exceeding
      170 cells/ microL rate of development of restenosis was 74% against 5% in
      patients with number of eosinophils less than 170 cells/ microL (p<0.001). Thus
      level of stromal progenitor cells in blood of patients with IHD was higher than
      in healthy persons and remained equally high in groups with and without
      restenosis. Number of blood eosinophilic leukocytes in patients who had been
      subjected to coronary stenting in whom later restenosis developed was
      significantly higher than in patients without restenosis. The data obtained
      indicate at the presence of link between development of in - stent restenosis and
      elevated content of eosinophilic granulocytes in blood of patients with IHD.

PMID- 20144157
TI  - [Disturbances of homocysteine metabolism as a risk factor of cardiovascular
      diseases development: effect on prognosis and possibilities of correction with
      drugs].
AB  - Classical risk factors of development of cardiovascular diseases does not allow
      to detect all persons needing active prevention. Because of this reason great
      attention is given to novel biomarkers one of which is homocysteine. Most widely
      spread causes of elevation of homocysteine level are such factors as deficit of
      folic acid and B6 and B12 vitamins, as well as genetic peculiarities. Main
      damaging effect of homocysteine is activation of atherothrombosis. Therapy with
      folic acid causes significant lowering of homocysteine level. Effect of therapy
      with vitamins on the risk of development of cardiovascular diseases has been
      assessed both in observational epidemiological studies and large prospective
      randomized trials. Their results are controversial. The present review is devoted
      to the analysis of these trials.

PMID- 20144158
TI  - [Acute coronary syndrome with ST segment depression on ECG: novel outlook of an
      old problem].
AB  - The lecture is devoted to morphological manifestations, clinical and prognostic
      features of acute coronary syndrome (ACS) with ST segment depressions on ECG. We
      have studied peculiarities of clinical course of this variant of ACS and its
      outcomes in 501 patients and suggested a scheme for stratification of patients in
      groups of risk of complicated course of ischemic heart disease. We have also
      studied 85 patients with ACS with ST segment depressions on ECG during anginal
      attack. In therapy of these patients we included drugs with potential metabolic
      action: trimetazidine (n=29), infusions of polarizing mixture (n=16), enalapril
      maleate (n=28), potassium succinate (n=12). It has been established that the
      application of trimetazidine improves course and prognosis of the disease.

PMID- 20144159
TI  - [A clinical experience of taurine and trimetazidine use in premenopausal women
      with chronic heart failure].

PMID- 20144160
TI  - [Safety of short-term discontinuation of antiplatelet therapy in patients with
      drug-eluting stents].

PMID- 20144161
TI  - [Ticagrelor versus clopidogrel in patients with acute coronary syndromes: results
      of the PLATO study].

PMID- 20144162
TI  - [Comparison of dronedarone and amiodarone for the maintenance of sinus rhythm in
      patients with atrial fibrillation. Indirect meta-analysis].

PMID- 20144163
TI  - [Contemporary approaches to echocardiographic assessment of left heart ventricle
      diastolic function].
AB  - Recommendations on echocardiographic diagnosis of diastolic function of the left
      ventricle of the heart are analyzed in this paper. Possibilities of
      echocardiography for early detection of disturbances of left ventricular
      relaxation and of pronounced derangements of diastolic function are shown.
      Difficulties of diagnostics of intermediate stages of diastolic dysfunction as
      well as ways of their solution are also considered. Together with presently
      existing methods of evaluation of severity of diastolic dysfunction which are
      based on assessment of transmitral blood flow a row of other Dopplerographic
      parameters are presented. Differential approach to assessment of diastolic
      function of the heart in dependence of the state of cardiac pump function is
      discussed. Prognostic value of abnormalities of diastole is presented too.

PMID- 20144164
TI  - [Ivabradine in the treatment of patients with angina pectoris: lessons of the
      BEAUTIFUL trial].
AB  - The article is devoted to results of additional analysis of a randomized, double
      blind, placebo-controlled, parallel-group BEAUTIFUL trial. Effects of If
      inhibitor ivabradine in patients with ischemic heart disease, left ventricular
      dysfunction and stable angina were analyzed.

PMID- 20144165
TI  - [Beta-adrenoblockers in arterial hypertension: focus on bisoprolol].

PMID- 20144166
TI  - Expression of aquaporin 8 is diversely regulated by osmotic stress in amnion
      epithelial cells.
AB  - AIM: Water absorption across fetal chorioamniotic membranes is a critical
      regulatory pathway for amniotic fluid volume homeostasis. Aquaporin 8 (AQP8) is a
      water channel regulating osmotic water travel across membranes. This study was to
      investigate the distribution and expression of AQP8 in amnion epithelial cells
      (AEC) in response to different osmotic stresses. METHODS: Cells derived from the
      amnion were subjected to different osmotic culture media. Reverse transcriptase
      polymerase chain reaction, Western blotting and immunofluorescence analysis were
      used to determine expression and localization of AQP8. RESULTS: Immunofluorescent
      staining confirmed the expression of AQP8 on cytomembrane and in cytoplasm.
      Hypotonic media increased AQP8 on cytomembrane of AEC. Compared to isosmolar
      media, hypotonic media significantly enhanced AQP8 mRNA and protein expression (P
      < 0.05), while hypertonic media significantly decreased expression (P < 0.05).
      CONCLUSION: The expression and distribution of AQP8 in AEC are diversely
      regulated by osmotic loads suggesting a role for AQP8 in intramembranous water
      transport and the balance of amniotic fluid.

PMID- 20144167
TI  - Short-term effects of closure versus non-closure of the visceral and parietal
      peritoneum at cesarean section: a prospective randomized study.
AB  - AIM: To determine the effect of non-closure of the visceral and parietal
      peritoneum during cesarean section on short-term postoperative morbidity.
      METHODS: A prospective randomized trial was conducted of 533 women undergoing
      primary cesarean section; 277 were randomized to closure and 256 to non-closure
      of the peritoneum. Perioperative outcome measures, such as analgesia dosage and
      morbidly measures were compared. RESULTS: There was no significant difference
      between the non-closure and closure groups in the mean number of narcotic
      analgesia doses (1.09 +/- 1.2 vs 1.05 +/- 1.0, P = 0.63; respectively), mean
      number of non-narcotic analgesia doses (4.69 +/- 2.7 vs 4.65 +/- 2.8, P = 0.89;
      respectively), number of women with postoperative fever >38 degrees C (18 vs 14,
      P = 0.37; respectively), number of women with wound infection (29 vs 35, P =
      0.54; respectively) and mean number of hospitalization days (4.16 +/- 0.91 vs
      4.14 +/- 0.71, P = 0.78; respectively). CONCLUSION: Closure or non-closure of the
      peritoneum at cesarean sections has no significant impact on postoperative
      analgesic usage and short-term morbidity.

PMID- 20144168
TI  - Three-dimensional ultrasonographic measurements of the fetal lungs for prediction
      of perinatal outcome in isolated congenital diaphragmatic hernia.
AB  - AIM: To evaluate the potential of different lung measurements using three
      dimensional ultrasonography (3D-US) to predict perinatal outcome in isolated
      congenital diaphragmatic hernia (CDH). METHODS: Twenty-one fetuses presenting
      isolated CDH were prospectively evaluated by 3D-US between January 2002 and
      November 2003. Observed/expected total, contralateral and ipsilateral fetal lung
      volume ratios (o/e-TotFLV, o/e-ContFLV and o/e-IpsiFLV, respectively) were
      calculated using the rotational technique and ultrasonographic fetal total lung
      volume to bodyweight ratio (USFLW). These lung measurements were compared to each
      other and to perinatal outcomes: perinatal deaths, severe pulmonary hypoplasia
      (PH) and pulmonary arterial hypertension (PAH). RESULTS: Perinatal death occurred
      in 11 of the 21 infants (52.4%), severe PH in 14 of 21 infants (66.7%) and PAH in
      14 of 20 neonates (70%). Severe PH and PAH occurred simultaneously in 12 of 20
      (60%) infants. Good correlations between lung ratios were observed. O/e-TotFLV,
      o/e-IpsiFLV and USFLW correlated statistically with postnatal diagnosis of severe
      PH, while only o/e-TotFLH correlated statistically with postnatal diagnosis of
      PAH. The accuracies of o/e-TotFLV, o/e-ContFLV, o/e-IpsiFLV and USFLW in
      predicting perinatal deaths were 85.7, 76.2, 66.7 and 76.2%, respectively.
      CONCLUSION: O/e-TotFLV using 3D-US appears to be the most accurate predictor of
      perinatal mortality because it can predict both PH and PAH.

PMID- 20144169
TI  - Perinatal outcome of recurrent pre-eclampsia versus pre-eclampsia in nulliparas.
AB  - AIM: The aim of the study was to compare the perinatal outcome of recurrent pre
      eclampsia in multiparas with that of pre-eclampsia in nulliparas. METHODS: This
      retrospective study was performed by collecting maternal and perinatal data from
      records of women with pre-eclampsia who delivered at Mackay Memorial Hospital
      over a 10-year period. Fifty women with recurrent pre-eclampsia were compared
      with 207 women who developed pre-eclampsia as nulliparas. In the 50 multiparas,
      the outcome of recurrent pre-eclampsia was also compared with that of their
      earlier episodes of pre-eclampsia. Maternal and fetal variables compared included
      maternal blood pressure, serum biochemistry, rate of preterm delivery, rate of
      abruptio placentae and neonatal outcome. RESULTS: Compared with nulliparous women
      with pre-eclampsia (n = 50), women with recurrent pre-eclampsia (n = 207) had a
      smaller increase in mean maternal blood pressure (27.0 +/- 18.9 mmHg vs 34.3 +/-
      19.3 mmHg, P = 0.021), less dipstick proteinuria (>or=++; 36.0 vs 58.5%, P =
      0.004), and bore children with a heavier mean birthweight (2909.1 +/- 895.5 g vs
      2551.1 +/- 933.0 g, P = 0.017). No significant statistical difference was found
      in the gestational age of delivery, maternal serum biochemical levels and rate of
      abruptio placentae or preterm delivery. Within the multiparous group (n = 50),
      recurrent disease was associated with a lower mean maternal blood pressure and
      dipstick proteinuria and with higher birthweight than in their previous pre
      eclamptic pregnancies. CONCLUSION: Recurrent pre-eclampsia appears to be less
      severe and to have a better perinatal outcome than pre-eclampsia in nulliparas.

PMID- 20144170
TI  - Serum prolidase activity and oxidative stress markers in pregnancies with
      intrauterine growth restricted infants.
AB  - AIM: To compare the levels of serum prolidase activity and oxidative stress
      markers, including total oxidative status (TOS), total antioxidant capacity
      (TAC), oxidative stress index (OSI), and total free sulfhydryl (-SH) in healthy
      pregnant women and pregnant women with intrauterine growth restricted infants.
      METHODS: Serum samples were obtained from 18 healthy third trimester pregnancies
      and 14 pregnancies complicated by fetal growth restriction (FGR). The criteria
      for FGR were clinical evidence of suboptimal growth, ultrasonographic
      demonstration of deviation from normal percentiles of growth, and birthweight
      under the 10th percentile. We spectrophotometrically measured serum prolidase
      activity, TAC, TOS, and -SH levels. Oxidative stress was determined from total
      antioxidant capacity and total oxidant status measurement and calculation of the
      oxidative stress index. RESULTS: Serum TAC and -SH levels were significantly
      lower in the FGR group than in the healthy control group (P = 0.001, P < 0.001,
      respectively), whereas TOS level, OSI value, and prolidase activity were
      significantly higher (P = 0.003, P < 0.001, P < 0.001, respectively). Prolidase
      activity was positively correlated with TOS and OSI values (rho = 0.552, P =
      0.041 and rho = 0.635, P = 0.015, respectively) and negatively correlated with
      TAC and -SH levels (rho = -0.578, P = 0.030 and rho = -0.622, P = 0.018,
      respectively). CONCLUSION: The present study shows that serum prolidase activity
      and oxidative stress are significantly associated with the presence of FGR and
      that the correlation between serum prolidase activity and markers of oxidative
      stress are represented as increased serum TOS level and decreased serum TAC and 
      SH levels, suggesting an association of collagen turnover and oxidative stress in
      vascular dysfunction.

PMID- 20144171
TI  - Sublingual versus vaginal misoprostol for induction of labor at term: a
      randomized prospective placebo-controlled study.
AB  - AIMS: To assess the effectiveness and safety of sublingual misoprostol (50
      microg), compared with the same dose administered vaginally every 6 h for
      cervical ripening and labor induction in women with a viable fetus in the third
      trimester of pregnancy. METHODS: This double-blind randomized prospective placebo
      controlled trial included 480 women with medical or obstetric indications for
      labor induction and undilated, uneffaced cervices. The patients were assigned
      randomly to receive 50 microg of sublingual or 50 microg of vaginal misoprostol
      every 6 h for 24 h. Maternal and neonatal outcome were analyzed. RESULTS: A total
      of 169 (70.4%) patients delivered vaginally in the sublingual group compared to
      160 (66.7%) in the vaginal group. The main indications for cesarean section in
      both groups were fetal distress (33/71 [46.4%] vs 38/80 [47.5%]), followed by
      failure of labor progress. Thirty three (13.8%) patients in the sublingual group
      had meconium staining of the amniotic fluid compared to 39 (16.3%) in the vaginal
      group. There was no difference between the groups regarding the induction-to
      delivery interval, duration of labor, neonatal outcome or maternal side-effects.
      CONCLUSION: Sublingual misoprostol is as effective as vaginal misoprostol for
      induction of labor at term. Moreover, the sublingual route is associated with a
      significantly higher patient satisfaction rate than vaginal misoprostol.

PMID- 20144172
TI  - Thrombophilia investigation in Malaysian women with recurrent pregnancy loss.
AB  - AIM: The status of thrombophilia in Asian women with recurrent pregnancy loss
      (RPL) is obscure and poorly understood. Numerous studies suggest the non
      existence or extreme rarity of the two important thrombophilia markers, factor V
      Leiden (FVL) and prothrombin G20210A (PTG) mutations, in patients of Asian
      ancestries. Thus, the consensus that thrombophilia is rare among Asians and
      laboratory investigations is irrelevant. We therefore investigated Malaysian
      women with RPL for thrombophilia abnormalities. METHODS: A total of 402 patients
      (RPL subjects) and 160 female controls were screened for FVL, PTG and methylene
      tetrahydrofolate reductase mutations using polymerase chain reaction, activated
      protein C resistance (APC-R) using clot-based tests, protein C and antithrombin
      using chromogenic tests, and protein S and antiphospholipid antibodies using
      enzyme-linked immunosorbent assays. RESULTS: APC-R was identified in 21.6%
      (87/402) of the RPL subjects. Of the 87 APC-R positive RPL subjects, 9.2% (8/87)
      were due to FVL, 51.7% (45/87) had protein S deficiency, 6.9% (6/87) had protein
      C deficiency, 6.9% (6/87) had combined protein S and protein C deficiencies, 1.1%
      (1/87) had antithrombin deficiency and 25.3% (22/87) had unidentifiable non
      specific abnormalities. Antiphospholipid antibodies were identified in 4.2%
      (17/402) of the RPL subjects. FVL (2% = 8/402) and PTG (0.5% = 2/402) were
      identified in the Malay and Indian RPL subjects, but there were none in the
      Chinese subjects or the controls. Methylene tetrahydrofolate reductase was
      identified in 35.3% (142/402) of the RPL subjects. CONCLUSIONS: Thrombophilia was
      identified in more than one-quarter (26.6% = 107/402) of the RPL subjects. APC-R
      not caused by FVL mutation was the most common thrombophilia marker in
      Malaysians, whereas in Caucasians it was the APC-R due to FVL mutation. The
      identification of FVL and PTG mutations in Malaysian women with RPL disputes
      prevailing evidences suggesting its non-occurrence in patients with Asian
      ancestries.

PMID- 20144173
TI  - Influence of red clover-derived isoflavones on serum lipid profile in
      postmenopausal women.
AB  - AIM: Menopause is associated with adverse metabolic changes, especially in plasma
      lipoprotein and cholesterol levels. Estrogens have beneficial effects on lipid
      metabolism. Phytoestrogens are plant substances that are structurally and
      functionally similar to 17beta-estradiol and are capable of producing estrogenic
      effects. The goal of the present study was to estimate the effects of red clover
      derived isoflavones on serum lipid levels in postmenopausal women. METHODS: The
      study comprised 40 healthy postmenopausal women with an average age of 56 years.
      The women were divided into two groups: 22 were allocated to a red clover-derived
      isoflavone medication group, and 18 were allocated to a non-medication group.
      Total blood cholesterol, cholesterol fractions and triglycerides in the women of
      both groups were investigated before treatment and at 4-month intervals over the
      following 12 months. RESULTS: Both total serum cholesterol and low-density
      lipoprotein (LDL) cholesterol levels, as well as triglyceride levels, were
      decreased significantly in the group receiving phytoestrogens. However, high
      density lipoprotein (HDL) cholesterol showed a significant increase. CONCLUSION:
      Red clover phytoestrogen supplementation in postmenopausal women had favorable
      metabolic effects on serum lipids. Furthermore, red clover phytoestrogens have no
      side-effects and can be considered safe.

PMID- 20144174
TI  - Efficacy and safety of human placenta extract in alleviating climacteric
      symptoms: prospective, randomized, double-blind, placebo-controlled trial.
AB  - AIM: To assess the efficacy and safety of human placenta extract in the relief of
      climacteric symptoms. METHODS: A prospective, randomized, double-blind, placebo
      controlled trial was performed on 108 women with menopausal symptoms. Human
      placenta extract or placebo was administered to the women for 4 weeks.
      Climacteric symptoms were assessed with the Kupperman Index (KMI). RESULTS: Both
      groups showed a significant reduction in the KMI score at the end of treatment.
      However, the decrease in the KMI score was significantly greater in the product
      group than in the placebo group (-12.30 +/- 10.44 vs -7.15 +/- 9.11, P = 0.012)
      after 4 weeks of treatment. The level of lipid profiles and liver function tests
      demonstrated no significant changes before and after treatment in both groups.
      CONCLUSION: Human placenta extract reduced climacteric symptoms more than the
      placebo. The safety evaluation showed a good safety and tolerability profile in
      the placenta extract group. The results of the present study suggest that human
      placenta extract can be an alternative therapy in women with menopausal symptoms.

PMID- 20144175
TI  - Pregnancy complicated with Alport syndrome: a good obstetric outcome and failure
      to diagnose an infant born to a mother with Alport syndrome by umbilical cord
      immunofluorescence staining.
AB  - Alport syndrome is a familial progressive nephritis. The most frequent type is X
      linked Alport syndrome, caused by genetic abnormalities in the alpha 5 chain of
      type IV collagen. Skin biopsy is a useful tool for diagnosing this disease. It is
      not well known how this syndrome affects pregnancy and how it is affected by
      pregnancy, or whether the umbilical cord may provide material for detecting this
      collagen abnormality. We report a primigravida with Alport syndrome with mild
      proteinuria who gave birth abdominally to a term male infant without
      deteriorating renal function during pregnancy. The umbilical cord from not only
      this infant but also from an Alport (-) control infant showed negative
      immunofluorescence staining for the alpha 5 chain of type IV collagen. Women with
      Alport syndrome without renal dysfunction may follow an uneventful obstetrical
      course until term. The cord may not be suitable for diagnosing Alport syndrome
      with immunofluorescence staining.

PMID- 20144176
TI  - Successful pregnancy outcome in a case of heterotopic intrauterine and cervical
      pregnancy and a literature review.
AB  - It is difficult to treat cervical pregnancy without harming the intrauterine
      pregnancy. We report the case of a patient who was 37 years old and had an
      abdominal myomectomy. She had become pregnant by in vitro fertilization and egg
      transfer, and was transferred because of massive bleeding at 6 weeks of
      gestation. Afterwards, Escherichia coli infection was detected and intravenous
      antibiotics were administered. Careful intracervical mass reduction and curettage
      were performed under abdominal ultrasound guidance. The postoperative course was
      uneventful and she gave birth by cesarean section at 38 weeks. Sixteen cases
      exist in the literature. Treatment of cervical pregnancy was performed by KCl
      injection in six cases, hyperosmotic glucose injection in one and complete
      cervical evacuation in nine. The nine patients that had cervical evacuation
      delivered at term. In seven cervical mass preservation cases, one patient with
      twin pregnancy delivered at 34 weeks, and six with singletons delivered at 31-36
      weeks. The best therapy is complete evacuation in early gestation in order to
      avoid infection, bleeding and premature birth. The authors emphasize abdominal
      ultrasound usage through the bladder window with 150-200 mL of water (or urine)
      for careful cervical mass reduction and curettage without harming the
      intrauterine pregnancy.

PMID- 20144177
TI  - A case of fulminant type 1 diabetes mellitus associated with pregnancy.
AB  - Fulminant type 1 diabetes associated with pregnancy is very rare. However if it
      occurs, the rapid onset is associated with an extremely high risk of fetal death.
      Therefore, it is important for physicians to make an appropriate diagnosis as
      early as possible and to begin immediate treatment of both the mother and the
      fetus. We report a case of fulminant type 1 diabetes associated with pregnancy in
      which a good outcome was achieved for both the mother and the fetus.

PMID- 20144178
TI  - Spontaneous uterine rupture during a second trimester pregnancy with a history of
      laparoscopic myomectomy.
AB  - Uterine rupture is one of the most feared obstetric complications, carrying an
      increased risk of maternal and perinatal morbidity and mortality. Here, we
      present a case of spontaneous uterine rupture during the first half of pregnancy.
      The patient did not report any recent trauma, however she had a history of
      laparoscopic myomectomy conducted three years earlier. The uterine rupture was 6
      7 cm in length, located at the fundal level and was thought to originate from the
      previous myomectomy scar. In this report, we discuss the importance of choosing
      the right surgical technique and suturing method in patients undergoing
      myomectomy who desire to conceive in the future, and how obscure the findings of
      uterine rupture during pregnancy can be.

PMID- 20144179
TI  - Rare form of extraovarian peritoneal serous papillary carcinoma with solitary
      tumor in the abdominal wall: a case report and literature review.
AB  - Cases of cancer presenting with microscopically confirmed metastatic malignancies
      for which no primary site can be detected are a challenge to stage clinically.
      Adenocarcinoma of unknown primary site is a subtype with high frequency that has
      no standard treatment and a poor prognosis. A 32-year-old female was found to
      have a tumor in the abdominal wall. Tumorectomy was conducted. A pathological
      examination indicated serous papillary adenocarcinoma, and peritoneal or ovarian
      cancer was suspected. Exploratory laparotomy and partial resection of the ovaries
      were carried out, but there were no malignant findings in the peritoneum, ovarian
      tissue or ascitic fluid. This is an extremely rare case of serous papillary
      adenocarcinoma with a cystic tumor that was categorized as extraovarian
      peritoneal serous papillary carcinoma (EPSPC) without other clinical findings.

PMID- 20144180
TI  - Exploring self-management characteristics in youths with type 1 diabetes
      mellitus: does membership in a glycemic control category matter?
AB  - BACKGROUND: Hemoglobin A1c (HbA1c) levels have been shown to worsen in
      adolescence and be related to long-term diabetes complications. Although
      categories of diabetes control (e.g., ideal, satisfactory, and poor) are
      routinely used in clinical practice, research has not fully explored whether
      these categories meaningfully distinguish between different self-management
      characteristics. OBJECTIVES: This study examines potential differences in self
      management characteristics for youths and their caregivers for three different
      categories of diabetes control (e.g., ideal, satisfactory, and poor control).
      METHODS: A total of 69 adolescents (35 M/34 F) with type 1 diabetes mellitus
      (T1DM) (aged 12-17 yr) and their caregivers completed questionnaires of readiness
      to change the balance of responsibility for diabetes tasks, family responsibility
      in diabetes management, and self-efficacy for diabetes. A medical record review
      yielded demographic information, most recent HbA1c level, and health care
      utilization over the past year. RESULTS: Youths in the three different categories
      of diabetes control demonstrated no significant differences on measures of self
      management characteristics. Maternal caregivers from the satisfactory control
      category and youths in the poor control category demonstrated the most consistent
      responses across various self-management characteristics. CONCLUSIONS: Youths
      classified in different categories of glycemic control may not be as different in
      their self-management characteristics as was presumed. Moreover, associations
      among self-management characteristics were not universal across responders.
      Therefore, individual assessments of youths' and caregivers' self-management
      characteristics need to occur independent of the youths' membership in a certain
      category of diabetes control.

PMID- 20144181
TI  - Hyperbaric oxygen therapy improves early posttransplant islet function.
AB  - OBJECTIVE: This study investigates the therapeutic potential of hyperbaric oxygen
      therapy (HBO) in reducing hypoxia and improving engraftment of intraportal islet
      transplants by promoting angiogenesis. METHODS: Diabetic BALB/c mice were
      transplanted with 500 syngeneic islets intraportally and received six consecutive
      twice-daily HBO treatments (n = 9; 100% oxygen for 1 h at 2.5 atmospheres
      absolute) after transplantation. Dynamic contrast-enhanced magnetic resonance
      imaging (DCE MRI) was used to assess new vessel formation at postoperative days
      (POD) 3, 7, and 14. Liver tissue was recovered at the same time points for
      correlative histology, including: hematoxylin and eosin, hypoxia-inducible factor
      (HIF1alpha), Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin
      nick end labeling (TUNEL), vascular endothelial growth factor (VEGF), and von
      Willebrand Factor immunohistochemistry. RESULTS: HBO therapy significantly
      reduced HIF-1alpha, TUNEL and VEGF expression in islets at POD 7. In the non-HBO
      transplants, liver enhancement on DCE MRI peaked at POD 7 consistent with less
      mature vasculature but this enhancement was suppressed at POD 7 in the HBO
      treated group. The number of new peri-islet vessels at POD 7 was not
      significantly different between HBO and control groups. CONCLUSION: These results
      are consistent with a hyperbaric oxygen-mediated decrease in hypoxia that
      appeared to enhance vessel maturation in the critical days following intraportal
      islet transplantation.

PMID- 20144182
TI  - Genomic and evolutionary comparisons of diazotrophic and pathogenic bacteria of
      the order Rhizobiales.
AB  - BACKGROUND: Species belonging to the Rhizobiales are intriguing and extensively
      researched for including both bacteria with the ability to fix nitrogen when in
      symbiosis with leguminous plants and pathogenic bacteria to animals and plants.
      Similarities between the strategies adopted by pathogenic and symbiotic
      Rhizobiales have been described, as well as high variability related to events of
      horizontal gene transfer. Although it is well known that chromosomal
      rearrangements, mutations and horizontal gene transfer influence the dynamics of
      bacterial genomes, in Rhizobiales, the scenario that determine pathogenic or
      symbiotic lifestyle are not clear and there are very few studies of comparative
      genomic between these classes of prokaryotic microorganisms trying to delineate
      the evolutionary characterization of symbiosis and pathogenesis. RESULTS: Non
      symbiotic nitrogen-fixing bacteria and bacteria involved in bioremediation closer
      to symbionts and pathogens in study may assist in the origin and ancestry genes
      and the gene flow occurring in Rhizobiales. The genomic comparisons of 19 species
      of Rhizobiales, including nitrogen-fixing, bioremediators and pathogens resulted
      in 33 common clusters to biological nitrogen fixation and pathogenesis, 15
      clusters exclusive to all nitrogen-fixing bacteria and bacteria involved in
      bioremediation, 13 clusters found in only some nitrogen-fixing and bioremediation
      bacteria, 01 cluster exclusive to some symbionts, and 01 cluster found only in
      some pathogens analyzed. In BBH performed to all strains studied, 77 common genes
      were obtained, 17 of which were related to biological nitrogen fixation and
      pathogenesis. Phylogenetic reconstructions for Fix, Nif, Nod, Vir, and Trb showed
      possible horizontal gene transfer events, grouping species of different
      phenotypes. CONCLUSIONS: The presence of symbiotic and virulence genes in both
      pathogens and symbionts does not seem to be the only determinant factor for
      lifestyle evolution in these microorganisms, although they may act in common
      stages of host infection. The phylogenetic analysis for many distinct operons
      involved in these processes emphasizes the relevance of horizontal gene transfer
      events in the symbiotic and pathogenic similarity.

PMID- 20144183
TI  - Trichomonas vaginalis vast BspA-like gene family: evidence for functional
      diversity from structural organisation and transcriptomics.
AB  - BACKGROUND: Trichomonas vaginalis is the most common non-viral human sexually
      transmitted pathogen and importantly, contributes to facilitating the spread of
      HIV. Yet very little is known about its surface and secreted proteins mediating
      interactions with, and permitting the invasion and colonisation of, the host
      mucosa. Initial annotations of T. vaginalis genome identified a plethora of
      candidate extracellular proteins. RESULTS: Data mining of the T. vaginalis genome
      identified 911 BspA-like entries (TvBspA) sharing TpLRR-like leucine-rich
      repeats, which represent the largest gene family encoding potential extracellular
      proteins for the pathogen. A broad range of microorganisms encoding BspA-like
      proteins was identified and these are mainly known to live on mucosal surfaces,
      among these T. vaginalis is endowed with the largest gene family. Over 190 TvBspA
      proteins with inferred transmembrane domains were characterised by a considerable
      structural diversity between their TpLRR and other types of repetitive sequences
      and two subfamilies possessed distinct classic sorting signal motifs for
      endocytosis. One TvBspA subfamily also shared a glycine-rich protein domain with
      proteins from Clostridium difficile pathogenic strains and C. difficile phages.
      Consistent with the hypothesis that TvBspA protein structural diversity implies
      diverse roles, we demonstrated for several TvBspA genes differential expression
      at the transcript level in different growth conditions. Identified variants of
      repetitive segments between several TvBspA paralogues and orthologues from two
      clinical isolates were also consistent with TpLRR and other repetitive sequences
      to be functionally important. For one TvBspA protein cell surface expression and
      antibody responses by both female and male T. vaginalis infected patients were
      also demonstrated. CONCLUSIONS: The biased mucosal habitat for microbial species
      encoding BspA-like proteins, the characterisation of a vast structural diversity
      for the TvBspA proteins, differential expression of a subset of TvBspA genes and
      the cellular localisation and immunological data for one TvBspA; all point to the
      importance of the TvBspA proteins to various aspects of T. vaginalis pathobiology
      at the host-pathogen interface.

PMID- 20144184
TI  - The effects of patient characteristics on ADHD diagnosis and treatment: a
      factorial study of family physicians.
AB  - BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a costly and
      prevalent disorder in the U.S., especially among youth. However, significant
      disparities in diagnosis and treatment appear to be predicted by the race and
      insurance status of patients. METHODS: This study employed a web-based factorial
      survey with four ADHD cases derived from an ADHD clinic, two diagnosed with ADHD
      in actual evaluation, and two not. Randomized measures included race and
      insurance status of the patients. Participants N = (187) included clinician
      members of regional and national practice-based research networks and the U.S.
      clinical membership of the Society of Teachers of Family Medicine. The main
      outcomes were decisions to 1) diagnose and 2) treat the cases, based upon the
      information presented, analyzed via binary logistic regression of the randomized
      factors and case indicators on diagnosis and treatment. RESULTS: ADHD-positive
      cases were 8 times more likely to be diagnosed and 12 times more likely to be
      treated, and the male ADHD positive case was more likely to be diagnosed and
      treated than the female ADHD positive case. Uninsured cases were significantly
      more likely to be treated overall, but male cases that were uninsured were about
      half as likely to be diagnosed and treated with ADHD. Additionally, African
      American race appears to increase the likelihood of medicinal treatment for ADHD
      and being both African-American and uninsured appears to cut the odds of
      medicinal treatment in half, but not significantly. CONCLUSIONS: Family
      physicians were competent at discerning between near-threshold ADHD-negative and
      ADHD positive cases. However, insurance status and race, as well as gender,
      appear to affect the likelihood of diagnosis and treatment for ADHD in Family
      Medicine settings.

PMID- 20144185
TI  - Facilitation of synaptic transmission and pain responses by CGRP in the amygdala
      of normal rats.
AB  - Calcitonin gene-related peptide (CGRP) plays an important role in peripheral and
      central sensitization. CGRP also is a key molecule in the spino-parabrachial
      amygdaloid pain pathway. Blockade of CGRP1 receptors in the spinal cord or in the
      amygdala has antinociceptive effects in different pain models. Here we studied
      the electrophysiological mechanisms of behavioral effects of CGRP in the amygdala
      in normal animals without tissue injury.Whole-cell patch-clamp recordings of
      neurons in the latero-capsular division of the central nucleus of the amygdala
      (CeLC) in rat brain slices showed that CGRP (100 nM) increased excitatory
      postsynaptic currents (EPSCs) at the parabrachio-amygdaloid (PB-CeLC) synapse,
      the exclusive source of CGRP in the amygdala. Consistent with a postsynaptic
      mechanism of action, CGRP increased amplitude, but not frequency, of miniature
      EPSCs and did not affect paired-pulse facilitation. CGRP also increased neuronal
      excitability. CGRP-induced synaptic facilitation was reversed by an NMDA receptor
      antagonist (AP5, 50 microM) or a PKA inhibitor (KT5720, 1 microM), but not by a
      PKC inhibitor (GF109203X, 1 microM). Stereotaxic administration of CGRP (10
      microM, concentration in microdialysis probe) into the CeLC by microdialysis in
      awake rats increased audible and ultrasonic vocalizations and decreased hindlimb
      withdrawal thresholds. Behavioral effects of CGRP were largely blocked by KT5720
      (100 microM) but not by GF109203X (100 microM).The results show that CGRP in the
      amygdala exacerbates nocifensive and affective behavioral responses in normal
      animals through PKA- and NMDA receptor-dependent postsynaptic facilitation. Thus,
      increased CGRP levels in the amygdala might trigger pain in the absence of tissue
      injury.

PMID- 20144186
TI  - Site-directed mutagenesis reveals a unique requirement for tyrosine residues in
      IL-7Ralpha and TSLPR cytoplasmic domains in TSLP-dependent cell proliferation.
AB  - BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7) like
      cytokine, which plays an important role in the regulation of immune responses to
      allergens. TSLP binds to a heterodimeric receptor complex composed of the IL-7
      receptor alpha chain (IL-7Ralpha) and the TSLP receptor (TSLPR, also known as
      CRLF2). It has previously been suggested that the lone tyrosine residue in the
      mouse TSLPR cytoplasmic domain is required for cell proliferation using chimeric
      receptor systems. Also the role of tyrosine residues in the IL-7Ralpha
      cytoplasmic domain in TSLP signaling has not yet been investigated. We undertook
      a systematic analysis to test the role of tyrosine residues of both the IL
      7Ralpha and the TSLPR in inducing cell proliferation in a growth factor dependent
      cell line, Ba/F3. RESULTS: A multiple sequence alignment of the IL-7Ralpha and
      TSLPR cytoplasmic domains revealed conservation of most, but not all, cytoplasmic
      tyrosine residues across several species. Our site-directed mutagenesis
      experiments revealed that the single tyrosine residue in human TSLPR was not
      required for TSLP-dependent cell proliferation. It has previously been reported
      that Y449 of human IL-7Ralpha is required for IL-7 dependent proliferation.
      Interestingly, in contrast to IL-7 signaling, none of tyrosine residues in the
      human IL-7Ralpha cytoplasmic domain were required for TSLP-dependent cell
      proliferation in the presence of a wild type TSLPR. However, the mutation of all
      cytoplasmic four tyrosine residues of human IL-7Ralpha and human TSLPR to
      phenylalanine residues abolished the proliferative ability of the TSLP receptor
      complex in response to TSLP. CONCLUSION: These results suggest that TSLP requires
      at least one cytoplasmic tyrosine residue to transmit proliferative signals.
      Unlike other members of IL-2 cytokine family, tyrosine residues in IL-7Ralpha and
      TSLPR cytoplasmic domains play a redundant role in TSLP-mediated cell growth.

PMID- 20144187
TI  - Spatial variability of climate effects on ischemic heart disease hospitalization
      rates for the period 1989-2006 in Quebec, Canada.
AB  - BACKGROUND: Studies have suggested an association between climate variables and
      circulatory diseases. The short-term effect of climate conditions on the
      incidence of ischemic heart disease (IHD) over the 1989-2006 period was examined
      for Quebec's 18 health regions. METHODS: Analyses were carried out for two age
      groups. A GAM statistical model, that blends the properties of generalized linear
      models with additive models, was used to fit the standardized daily
      hospitalization rates for IHD and their relationship with climatic conditions up
      to two weeks prior to the day of admission, controlling for time trends, day of
      the season and gender. RESULTS: Results show that, in most of Quebec's regions,
      cold temperatures during winter months and hot episodes during the summer months
      are associated with an increase of up to 12% in the daily hospital admission rate
      for IHD but also show decreased risks in some areas. The risk of hospitalization
      is higher for men and women of 45-64 years and varies spatially. In most regions,
      exposure to a continuous period of cold or hot temperature was more harmful than
      just one isolated day of extreme weather. Men aged 45-64 years showed higher risk
      levels of IHD than women of the same age group. In most regions, the annual
      maximum of daily IHD admissions for 65 years old was reached earlier in the
      season for both genders and both seasons compared to younger age groups. The
      effects of meteorological variables on the daily IHD admissions rate were more
      pronounced in regions with high smoking prevalence and high deprivation index.
      CONCLUSION: This study highlights the differential effects of cold and hot
      periods on IHD in Quebec health regions depending on age, sex, and other factors
      such as smoking, behaviour and deprivation levels.

PMID- 20144188
TI  - The TOPGAME-study: effectiveness of extracorporeal shockwave therapy in jumping
      athletes with patellar tendinopathy. Design of a randomised controlled trial.
AB  - BACKGROUND: Patellar tendinopathy is a major problem for many athletes,
      especially those involved in jumping activities. Despite its frequency and
      negative impact on athletic careers, no evidence-based guidelines for management
      of this overuse injury exist. Since functional outcomes of conservative and
      surgical treatments remain suboptimal, new diagnostic and therapeutic strategies
      have to be developed and evaluated. Extracorporeal shockwave therapy (ESWT)
      appears to be a promising treatment in patients with chronic patellar
      tendinopathy. ESWT is most often applied after the known conservative treatments
      have failed. However, its effectiveness as primary therapy has not been studied
      in athletes who keep playing sports despite having patellar tendon pain. The aim
      of this study is to determine the effectiveness of ESWT in athletes with patellar
      tendinopathy who are still in training and competition. METHODS/DESIGN: The
      TOPGAME-study (Tendinopathy of Patella Groningen Amsterdam Maastricht ESWT) is a
      multicentre two-armed randomised controlled trial with blinded participants and
      outcome assessors, in which the effectiveness of patient-guided focussed ESWT
      treatment (compared to placebo ESWT) on pain reduction and recovery of function
      in athletes with patellar tendinopathy will be investigated. Participants are
      volleyball, handball and basketball players with symptoms of patellar
      tendinopathy for a minimum of 3 to a maximum duration of 12 months who are still
      able to train and compete. The intervention group receives three patient-guided
      focussed medium-energy density ESWT treatments without local anaesthesia at a
      weekly interval in the first half of the competition. The control group receives
      placebo treatment. The follow-up measurements take place 1, 12 and 22 weeks after
      the final ESWT or placebo treatment, when athletes are still in competition.
      Primary outcome measure is the VISA-P (Victorian Institute of Sport Assessment -
      patella) score. Data with regard to pain during function tests (jump tests and
      single-leg decline squat) and ultrasound characteristics are also collected.
      During the follow-up period participants also register pain, symptoms, sports
      participation, side effects of treatment and additional medical consumption in an
      internet-based diary. DISCUSSION: The TOPGAME-study is the first RCT to study the
      effectiveness of patient-guided ESWT in athletes with patellar tendinopathy who
      are still in training and competition. TRIAL REGISTRATION: Trial registration
      number NTR1408.

PMID- 20144189
TI  - Comparative transfection of DNA into primary and transformed mammalian cells from
      different lineages.
AB  - BACKGROUND: The delivery of DNA into human cells has been the basis of advances
      in the understanding of gene function and the development of genetic therapies.
      Numerous chemical and physical approaches have been used to deliver the DNA, but
      their efficacy has been variable and is highly dependent on the cell type to be
      transfected. RESULTS: Studies were undertaken to evaluate and compare the
      transfection efficacy of several chemical reagents to that of the
      electroporation/nucleofection system using both adherent cells (primary and
      transformed airway epithelial cells and primary fibroblasts as well as embryonic
      stem cells) and cells in suspension (primary hematopoietic stem/progenitor cells
      and lymphoblasts). With the exception of HEK 293 cell transfection, nucleofection
      proved to be less toxic and more efficient at effectively delivering DNA into the
      cells as determined by cell proliferation and GFP expression, respectively.
      Lipofectamine and nucleofection of HEK 293 were essentially equivalent in terms
      of toxicity and efficiency. Transient transfection efficiency in all the cell
      systems ranged from 40%-90%, with minimal toxicity and no apparent species
      specificity. Differences in efficiency and toxicity were cell type/system
      specific. CONCLUSIONS: In general, the Amaxa electroporation/nucleofection system
      appears superior to other chemical systems. However, there are cell-type and
      species specific differences that need to be evaluated empirically to optimize
      the conditions for transfection efficiency and cell survival.

PMID- 20144190
TI  - Building generic anatomical models using virtual model cutting and iterative
      registration.
AB  - BACKGROUND: Using 3D generic models to statistically analyze trends in biological
      structure changes is an important tool in morphometrics research. Therefore, 3D
      generic models built for a range of populations are in high demand. However, due
      to the complexity of biological structures and the limited views of them that
      medical images can offer, it is still an exceptionally difficult task to quickly
      and accurately create 3D generic models (a model is a 3D graphical representation
      of a biological structure) based on medical image stacks (a stack is an ordered
      collection of 2D images). We show that the creation of a generic model that
      captures spatial information exploitable in statistical analyses is facilitated
      by coupling our generalized segmentation method to existing automatic image
      registration algorithms. METHODS: The method of creating generic 3D models
      consists of the following processing steps: (i) scanning subjects to obtain image
      stacks; (ii) creating individual 3D models from the stacks; (iii) interactively
      extracting sub-volume by cutting each model to generate the sub-model of
      interest; (iv) creating image stacks that contain only the information pertaining
      to the sub-models; (v) iteratively registering the corresponding new 2D image
      stacks; (vi) averaging the newly created sub-models based on intensity to produce
      the generic model from all the individual sub-models. RESULTS: After several
      registration procedures are applied to the image stacks, we can create averaged
      image stacks with sharp boundaries. The averaged 3D model created from those
      image stacks is very close to the average representation of the population. The
      image registration time varies depending on the image size and the desired
      accuracy of the registration. Both volumetric data and surface model for the
      generic 3D model are created at the final step. CONCLUSIONS: Our method is very
      flexible and easy to use such that anyone can use image stacks to create models
      and retrieve a sub-region from it at their ease. Java-based implementation allows
      our method to be used on various visualization systems including personal
      computers, workstations, computers equipped with stereo displays, and even
      virtual reality rooms such as the CAVE Automated Virtual Environment. The
      technique allows biologists to build generic 3D models of their interest quickly
      and accurately.

PMID- 20144191
TI  - Testing the additional predictive value of high-dimensional molecular data.
AB  - BACKGROUND: While high-dimensional molecular data such as microarray gene
      expression data have been used for disease outcome prediction or diagnosis
      purposes for about ten years in biomedical research, the question of the
      additional predictive value of such data given that classical predictors are
      already available has long been under-considered in the bioinformatics
      literature. RESULTS: We suggest an intuitive permutation-based testing procedure
      for assessing the additional predictive value of high-dimensional molecular data.
      Our method combines two well-known statistical tools: logistic regression and
      boosting regression. We give clear advice for the choice of the only method
      parameter (the number of boosting iterations). In simulations, our novel approach
      is found to have very good power in different settings, e.g. few strong
      predictors or many weak predictors. For illustrative purpose, it is applied to
      the two publicly available cancer data sets. CONCLUSIONS: Our simple and
      computationally efficient approach can be used to globally assess the additional
      predictive power of a large number of candidate predictors given that a few
      clinical covariates or a known prognostic index are already available. It is
      implemented in the R package "globalboosttest" which is publicly available from R
      forge and will be sent to the CRAN as soon as possible.

PMID- 20144192
TI  - Chromosome 7p linkage and association study for diabetes related traits and type
      2 diabetes in an African-American population enriched for nephropathy.
AB  - BACKGROUND: Previously we performed a linkage scan of 638 African American
      affected sibling pairs (ASP) with type 2 diabetes (T2D) enriched for end-stage
      renal disease (ESRD). Ordered subset linkage analysis (OSA) revealed a linkage
      peak on chromosome 7p in the subset of families with earlier age of T2D
      diagnosis. METHODS: We fine mapped this region by genotyping 11 additional
      polymorphic markers in the same ASP and investigated a total of 68 single
      nucleotide polymorphisms (SNPs) in functional candidate genes (GCK1, IL6, IGFBP1
      and IGFBP3) for association with age of T2D diagnosis, age of ESRD diagnosis,
      duration of T2D to onset of ESRD, body mass index (BMI) in African American cases
      and T2D-ESRD in an African American case-control cohort. OSA of fine mapping
      markers supported linkage at 28 cM on 7p (near D7S3051) in early-onset T2D
      families (max. LOD = 3.61, P = 0.002). SNPs in candidate genes and 70 ancestry
      informative markers (AIMs) were evaluated in 577 African American T2D-ESRD cases
      and 596 African American controls. RESULTS: The most significant association was
      observed between ESRD age of diagnosis and SNP rs730497, located in intron 1 of
      the GCK1 gene (recessive T2D age-adjusted P = 0.0006). Nominal associations were
      observed with GCK1 SNPs and T2D age of diagnosis (BMI-adjusted P = 0.014 to
      0.032). Also, one IGFBP1 and four IGFBP3 SNPs showed nominal genotypic
      association with T2D-ESRD (P = 0.002-0.049). After correcting for multiple tests,
      only rs730497 remanined significant. CONCLUSION: Variant rs730947 in the GCK1
      gene appears to play a role in early ESRD onset in African Americans.

PMID- 20144193
TI  - Posttraumatic stress, anxiety and depression symptoms in patients during the
      first year post intensive care unit discharge.
AB  - INTRODUCTION: To study the level and predictors of posttraumatic stress, anxiety
      and depression symptoms in medical, surgical and trauma patients during the first
      year post intensive care unit (ICU) discharge. METHODS: Of 255 patients included,
      194 participated at 12 months. Patients completed the Impact of Event Scale
      (IES), Hospital Anxiety and Depression Scale (HADS), Life Orientation Test (LOT)
      at 4 to 6 weeks, 3 and 12 months and ICU memory tool at the first assessment
      (baseline). Case level for posttraumatic stress symptoms with high probability of
      a posttraumatic stress disorder (PTSD) was > or = 35. Case level of HADS-Anxiety
      or Depression was > or = 11. Memory of pain during ICU stay was measured at
      baseline on a five-point Likert-scale (0-low to 4-high). Patient demographics and
      clinical variables were controlled for in logistic regression analyses. RESULTS:
      Mean IES score one year after ICU treatment was 22.5 (95%CI 20.0 to 25.1) and 27%
      (48/180) were above case level, IES > or = 35. No significant differences in the
      IES mean scores across the three time points were found (P = 0.388). In a
      subgroup, 27/170 (16%), patients IES score increased from 11 to 32, P < 0.001. No
      differences in posttraumatic stress, anxiety or depression between medical,
      surgical and trauma patients were found. High educational level (OR 0.4, 95%CI
      0.2 to 1.0), personality trait (optimism) OR 0.9, 95%CI 0.8 to 1.0), factual
      recall (OR 6.6, 95%CI 1.4 to 31.0) and memory of pain (OR 1.5, 95%CI 1.1 to 2.0)
      were independent predictors of posttraumatic stress symptoms at one year.
      Optimism was a strong predictor for less anxiety (OR 0.8, 0.8 to 0.9) and
      depression symptoms (OR 0.8, 0.8 to 0.9) after one year. CONCLUSIONS: The mean
      level of posttraumatic stress symptoms in patients one year following ICU
      treatment was high and one of four were above case level Predictors of
      posttraumatic stress symptoms were mainly demographics and experiences during
      hospital stay whereas clinical injury related variables were insignificant.
      Pessimism was a predictor of posttraumatic stress, anxiety and depression
      symptoms. A subgroup of patients developed clinically significant distress
      symptoms during the follow-up period.

PMID- 20144194
TI  - Using simple artificial intelligence methods for predicting amyloidogenesis in
      antibodies.
AB  - BACKGROUND: All polypeptide backbones have the potential to form amyloid fibrils,
      which are associated with a number of degenerative disorders. However, the
      likelihood that amyloidosis would actually occur under physiological conditions
      depends largely on the amino acid composition of a protein. We explore using a
      naive Bayesian classifier and a weighted decision tree for predicting the
      amyloidogenicity of immunoglobulin sequences. RESULTS: The average accuracy based
      on leave-one-out (LOO) cross validation of a Bayesian classifier generated from
      143 amyloidogenic sequences is 60.84%. This is consistent with the average
      accuracy of 61.15% for a holdout test set comprised of 103 AM and 28 non
      amyloidogenic sequences. The LOO cross validation accuracy increases to 81.08%
      when the training set is augmented by the holdout test set. In comparison, the
      average classification accuracy for the holdout test set obtained using a
      decision tree is 78.64%. Non-amyloidogenic sequences are predicted with average
      LOO cross validation accuracies between 74.05% and 77.24% using the Bayesian
      classifier, depending on the training set size. The accuracy for the holdout test
      set was 89%. For the decision tree, the non-amyloidogenic prediction accuracy is
      75.00%. CONCLUSIONS: This exploratory study indicates that both classification
      methods may be promising in providing straightforward predictions on the
      amyloidogenicity of a sequence. Nevertheless, the number of available sequences
      that satisfy the premises of this study are limited, and are consequently smaller
      than the ideal training set size. Increasing the size of the training set clearly
      increases the accuracy, and the expansion of the training set to include not only
      more derivatives, but more alignments, would make the method more sound. The
      accuracy of the classifiers may also be improved when additional factors, such as
      structural and physico-chemical data, are considered. The development of this
      type of classifier has significant applications in evaluating engineered
      antibodies, and may be adapted for evaluating engineered proteins in general.

PMID- 20144195
TI  - Decreased NPC1L1 expression in the liver from Chinese female gallstone patients.
AB  - BACKGROUND: Cholesterol gallstone disease is a very common disease in both
      industrialized and developing countries. Many studies have found that cholesterol
      gallstones are more common in women than men. The molecular mechanisms underlying
      the relationship between female gallstone disease and hepatic sterol transporters
      are still undergoing definition and have not been evaluated in humans. AIMS: The
      aim of this study is to probe for underlying hepatic molecular defects associated
      with development of gallstones in female. METHODS/RESULTS: Fifty-seven nonobese,
      normolipidemic Chinese female gallstone patients (GS) were investigated with 12
      age- and body mass index-matched female gallstone-free controls (GSF). The bile
      from the female GS had higher cholesterol saturation than that from the female
      GSF. The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with
      SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels. Consistently,
      immunohistochemistry showed decreased NPC1L1 expression in female GS.
      CONCLUSIONS: The decreased hepatic NPC1L1 levels in female GS might indicate a
      downregulated reabsorption of biliary cholesterol in the liver, which, in turn,
      leads to the cholesterol supersaturation of bile. Our data are consistent with
      the possibility that hepatic NPC1L1 may be mediated by SREBP2.

PMID- 20144196
TI  - Transcriptional profiling reveals the expression of novel genes in response to
      various stimuli in the human dermatophyte Trichophyton rubrum.
AB  - BACKGROUND: Cutaneous mycoses are common human infections among healthy and
      immunocompromised hosts, and the anthropophilic fungus Trichophyton rubrum is the
      most prevalent microorganism isolated from such clinical cases worldwide. The aim
      of this study was to determine the transcriptional profile of T. rubrum exposed
      to various stimuli in order to obtain insights into the responses of this
      pathogen to different environmental challenges. Therefore, we generated an
      expressed sequence tag (EST) collection by constructing one cDNA library and nine
      suppression subtractive hybridization libraries. RESULTS: The 1388 unigenes
      identified in this study were functionally classified based on the Munich
      Information Center for Protein Sequences (MIPS) categories. The identified
      proteins were involved in transcriptional regulation, cellular defense and
      stress, protein degradation, signaling, transport, and secretion, among other
      functions. Analysis of these unigenes revealed 575 T. rubrum sequences that had
      not been previously deposited in public databases. CONCLUSION: In this study, we
      identified novel T. rubrum genes that will be useful for ORF prediction in genome
      sequencing and facilitating functional genome analysis. Annotation of these
      expressed genes revealed metabolic adaptations of T. rubrum to carbon sources,
      ambient pH shifts, and various antifungal drugs used in medical practice.
      Furthermore, challenging T. rubrum with cytotoxic drugs and ambient pH shifts
      extended our understanding of the molecular events possibly involved in the
      infectious process and resistance to antifungal drugs.

PMID- 20144197
TI  - Construct validation of a non-exercise measure of cardiorespiratory fitness in
      older adults.
AB  - BACKGROUND: Cardiorespiratory fitness (CRF) is associated with a decreased risk
      of all-cause mortality but is rarely assessed in medical settings due to burdens
      of time, cost, risk, and resources. The purpose of this study was to test the
      construct validity of a regression equation developed by Jurca and colleagues
      (2005) to estimate CRF without exercise testing in community dwelling older
      adults. METHODS: Participants (n = 172) aged 60 to 80 years with no
      contraindications to submaximal or maximal exercise testing completed a maximal
      graded exercise test (GXT) and the submaximal Rockport 1-mile walk test on
      separate occasions. Data included in the regression equation (age, sex, body mass
      index, resting heart rate, and physical activity) were obtained via measurement
      or self-report. Participants also reported presence of cardiovascular conditions.
      RESULTS: The multiple R for the regression equation was .72, p < .001 and CRF
      estimated from this equation was significantly correlated with the MET value from
      the GXT (r = 0.66) and with CRF estimated from submaximal field testing (r =
      0.67). All three CRF indices were significantly and inversely associated with
      reporting more cardiovascular conditions. CONCLUSIONS: This research provides
      preliminary evidence that a non-exercise estimate of CRF is at least as valid as
      field test estimates of CRF and represents a low-risk, low-cost, and expedient
      method for estimating fitness in older adults.

PMID- 20144198
TI  - Parameters for accurate genome alignment.
AB  - BACKGROUND: Genome sequence alignments form the basis of much research. Genome
      alignment depends on various mundane but critical choices, such as how to mask
      repeats and which score parameters to use. Surprisingly, there has been no large
      scale assessment of these choices using real genomic data. Moreover, rigorous
      procedures to control the rate of spurious alignment have not been employed.
      RESULTS: We have assessed 495 combinations of score parameters for alignment of
      animal, plant, and fungal genomes. As our gold-standard of accuracy, we used
      genome alignments implied by multiple alignments of proteins and of structural
      RNAs. We found the HOXD scoring schemes underlying alignments in the UCSC genome
      database to be far from optimal, and suggest better parameters. Higher values of
      the X-drop parameter are not always better. E-values accurately indicate the rate
      of spurious alignment, but only if tandem repeats are masked in a non-standard
      way. Finally, we show that gamma-centroid (probabilistic) alignment can find
      highly reliable subsets of aligned bases. CONCLUSIONS: These results enable more
      accurate genome alignment, with reliability measures for local alignments and for
      individual aligned bases. This study was made possible by our new software, LAST,
      which can align vertebrate genomes in a few hours http://last.cbrc.jp/.

PMID- 20144199
TI  - EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and
      a worse prognosis.
AB  - BACKGROUND: About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus
      (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV
      encoded small RNAs (EBERs) are presented in all EBV-infected cells, but their
      functions are still less understood. RESULTS: EBER1 was transfected into two HL
      cell lines, KMH2 and L428, and microarrays were used to screen for EBER1-induced
      changes. We found that EBER1 suppressed p21cip1/waf1 transcription in HL cell
      lines. In addition, positive regulators of p21cip1/waf1 transcription, such as
      p53, EGR1, and STAT1, were decreased. Suppression of p21cip1/waf1 in the EBER1+
      HL cell lines was associated with increased resistance to histone deacetylase
      inhibitors or proteasome inhibitors, drugs known to cause apoptosis by increasing
      p21cip1/waf1 levels. On biopsy specimens, EBV+ HLs had weaker expression of both
      p21cip1/waf1 and active caspase 3. Clinically, suppression of p21cip1/waf1 in
      EBV+ HLs was associated with a worse 2-year disease-free survival rate (45% for
      EBV+ HLs vs. 77% for EBV- HLs, p = 0.002). CONCLUSION: Although the underlying
      mechanisms are still relatively unclear, EBER1 inhibits p21cip1/waf1
      transcription and prevents apoptosis through down-regulation of p53, EGR1, and
      STAT1. The anti-apoptotic activity of EBER1 may be important in the rescue of
      Reed-Sternberg cells from drug-induced apoptosis and in the clinical behaviors of
      EBV+ HLs.

PMID- 20144200
TI  - Annotation and classification of the bovine T cell receptor delta genes.
AB  - BACKGROUND: gammadelta T cells differ from alphabeta T cells with regard to the
      types of antigen with which their T cell receptors interact; gammadelta T cell
      antigens are not necessarily peptides nor are they presented on MHC. Cattle are
      considered a "gammadelta T cell high" species indicating they have an increased
      proportion of gammadelta T cells in circulation relative to that in "gammadelta T
      cell low" species such as humans and mice. Prior to the onset of the studies
      described here, there was limited information regarding the genes that code for
      the T cell receptor delta chains of this gammadelta T cell high species. RESULTS:
      By annotating the bovine (Bos taurus) genome Btau_3.1 assembly the presence of 56
      distinct T cell receptor delta (TRD) variable (V) genes were found, 52 of which
      belong to the TRDV1 subgroup and were co-mingled with the T cell receptor alpha
      variable (TRAV) genes. In addition, two genes belonging to the TRDV2 subgroup and
      single TRDV3 and TRDV4 genes were found. We confirmed the presence of five
      diversity (D) genes, three junctional (J) genes and a single constant (C) gene
      and describe the organization of the TRD locus. The TRDV4 gene is found
      downstream of the C gene and in an inverted orientation of transcription,
      consistent with its orthologs in humans and mice. cDNA evidence was assessed to
      validate expression of the variable genes and showed that one to five D genes
      could be incorporated into a single transcript. Finally, we grouped the bovine
      and ovine TRDV1 genes into sets based on their relatedness. CONCLUSIONS: The
      bovine genome contains a large and diverse repertoire of TRD genes when compared
      to the genomes of "gammadelta T cell low" species. This suggests that in cattle
      gammadelta T cells play a more important role in immune function since they would
      be predicted to bind a greater variety of antigens.

PMID- 20144201
TI  - Chronic infection during placental malaria is associated with up-regulation of
      cycloxygenase-2.
AB  - BACKGROUND: Placental malaria (PM) is associated with poor foetal development,
      but the pathophysiological processes involved are poorly understood.
      Cyclooxygenase (COX) and lipoxygenase (LOX) which convert fatty acids to
      prostaglandins and leukotrienes, play important roles in pregnancy and foetal
      development. COX-2, currently targeted by specific drugs, plays a dual role as it
      associates with both pre-eclampsia pathology and recovery during infection. The
      role of COX during PM was questioned by quantifying at delivery COX-1, COX-2, 15
      LOX, and IL-10 expression in two groups of malaria infected and uninfected
      placenta. METHODS: Placental biopsies were collected at delivery for mRNA
      isolation and quantification, using real time PCR. RESULTS: COX-2 and IL-10 mRNAs
      increased mainly during chronic infections (nine- and five-times, respectively),
      whereas COX-1 transcripts remained constant. COX-2 over-expression was associated
      with a higher birth weight of the baby, but with a lower rate of haemoglobin of
      the mother. It was associated with a macrophage infiltration of the placenta and
      with a low haemozoin infiltration. In the opposite way, placental infection was
      associated with lower expression of 15-LOX mRNA. A high degree of haemozoin
      deposition correlates with low birth weight and decreased expression of COX-2.
      CONCLUSION: These data provide evidence that COX-2 and IL-10 are highly induced
      during chronic infection of the placenta, but were not associated with preterm
      delivery or low birth weight. The data support the involvement of COX-2 in the
      recovery phase of the placental infection.

PMID- 20144202
TI  - PFGE diversity within the methicillin-resistant Staphylococcus aureus clonal
      lineage ST398.
AB  - BACKGROUND: Livestock has recently been identified as a new reservoir of
      methicillin-resistant Staphylococcus aureus (MRSA). Most isolates belong to ST398
      and are non-typeable with PFGE using SmaI, making it difficult to study
      transmission and outbreaks. Therefore, a new PFGE using Cfr9I, a neoschizomer of
      SmaI was optimized and evaluated to investigate ST398 isolates. RESULTS: After
      optimizing and evaluating the Cfr9I PFGE, clear and reproducible banding patterns
      were obtained from all previously non-typeable MRSA (NT(SmaI) -MRSA) isolates.
      The PFGE patterns of ST398 isolates showed more diversity than with spa-typing
      and/or MLST. The PFGE results showed diversity within and between the two most
      prevalent spa-types of NT(SmaI) -MRSA (t011 and t108). No match was found, when
      comparing banding patterns of the NT(SmaI) -MRSA with 700 different PFGE types,
      obtained with SmaI digestion, in our database of more than 4000 strains.
      Furthermore, possible transmission among veterinarians and their family members
      was investigated and an outbreak of ST398 MRSA in a residential care facility was
      confirmed with the Cfr9I PFGE. CONCLUSIONS: The adjusted PFGE can be used as a
      method for selecting important and distinct ST398 isolates for further research.
      The adjustments in the PFGE protocol using Cfr9I are easy to implement to study
      the ST398 clonal lineage in laboratories which already have a PFGE facility.

PMID- 20144203
TI  - The Manchester Color Wheel: development of a novel way of identifying color
      choice and its validation in healthy, anxious and depressed individuals.
AB  - BACKGROUND: For the purposes of our research programme we needed a simple,
      reliable and validated method for allowing choice of a color in response to a
      series of questions. On reviewing the literature no such instrument was available
      and this study aimed to rectify this situation. This was achieved by developing a
      simple method of presenting a series of colors to people validating it in healthy
      volunteers and in individuals where color choice might be distorted, namely
      anxiety and depression. METHODS: A series of different presentations of four
      shades of eight colors and grey, as well as black and white were evaluated.
      'Mood', 'favourite' and 'drawn to' colors were assessed in 105 healthy, 108
      anxious and 110 depressed participants. The positive, neutral or negative
      attribution of these colors was recorded in a further 204 healthy volunteers.
      RESULTS: The circular presentation of colors was most favoured (Color Wheel).
      Yellow was the most 'drawn to' color and blue the commonest 'favourite' color in
      all subjects. Yellow was most often associated with a normal mood and grey with
      an anxious or depressed mood. Different shades of the same color had completely
      different positive or negative connotations. Reproducibility was exceptionally
      high when color choice was recorded in positive, neutral or negative terms.
      CONCLUSIONS: The Color Wheel could be used to assess health status, mood or even
      treatment outcome in a variety of clinical situations. It may also have utility
      in circumstances where verbal communication may not be optimal, such as with
      children.

PMID- 20144204
TI  - The association between use of electronic media and prevalence of headache in
      adolescents: results from a population-based cross-sectional study.
AB  - BACKGROUND: Use of electronic media, i.e. mobile phones, computers, television,
      game consoles or listening to music, is very common, especially amongst
      adolescents. There is currently a debate about whether frequent use of these
      media might have adverse effects on health, especially on headaches, which are
      among the most-reported health complaints in adolescents. The aim of the present
      study was to assess associations between frequent use of electronic media and the
      prevalence of different types of headache in adolescents. METHODS: Data were
      derived from a population-based sample (n = 1,025, ages 13-17 years). Type of
      headache (i.e. migraine, tension-type headache, unclassifiable headache) was
      ascertained by standardized questionnaires for subjects reporting headache
      episodes at least once per month during the last six months. Duration of
      electronic media use was assessed during personal interviews. Associations were
      estimated with logistic regression models adjusted for age group, sex, family
      condition and socio-economic status. RESULTS: Most of the adolescents used
      computers (85%), watched television (90%) or listened to music (90%) daily,
      otherwise only 23% of the participants used their mobile phones and only 25%
      played with game consoles on a daily basis. A statistically significant
      association between listening to music and any headache (odds ratio 1.8; 95%
      confidence interval 1.1-3.1 for 30 minutes per day, 2.1; 1.2-3.7 for 1 to 2 hours
      per day; 2.0; 1.2-3.5 for 3 hours and longer listening to music per day) was
      observed. When stratifying for type of headache, no statistically significant
      association was seen. CONCLUSIONS: Apart from an association between listening to
      music on a daily basis and overall headache, no consistent associations between
      the use of electronic media and different types of headache were observed.

PMID- 20144205
TI  - General practitioners' opinions on how to improve treatment of mental disorders
      in primary health care. Interviews with one hundred Norwegian general
      practitioners.
AB  - BACKGROUND: Improvements in treatment of mental disorders are repeatedly called
      for. General practitioners (GPs) are responsible for the majority of treatment of
      mental disorders. Consequently, we interviewed GPs about their opinions on how
      treatment of mental disorders in primary health care contexts could be improved.
      METHODS: Among GPs affiliated within the Norwegian reimbursement system, we
      approached 353, and made contact with 246 GP's. One-hundred of these agreed to
      participate in our study, and 95 of them expressed opinions on how to improve
      treatment of mental disorders. The telephone interviews were based on open-ended
      questions, responses were transcribed continuously, and content analysis was
      applied. Results are presented both as frequency tables of common responses, and
      as qualitative descriptions and quotations of opinions. RESULTS: Nearly all (95%)
      of the GPs had suggestions on how to improve treatment of mental disorders in
      primary health care. Increased capacity in secondary health care was suggested by
      59% of GPs. Suggestions of improved collaboration with secondary health care were
      also common (57%), as were improvements of GPs' skills and knowledge relevant for
      diagnosing and treating mental disorders (40%) and more time for patients with
      mental disorders in GP contexts (40%). CONCLUSIONS: The GPs' suggestions are in
      line with international research and debate. It is thought-provoking that the
      majority of GPs call for increased capacity in secondary care, and also better
      collaboration with secondary care. Some GPs made comparisons to the health care
      system for physical disorders, which is described as better-functioning. Our
      study identified no simple short-term cost-effective interventions likely to
      improve treatment for mental disorders within primary health care. Under
      treatment of mental disorders is, however, also associated with significant
      financial burdens.

PMID- 20144206
TI  - Apoptosis of resident and inflammatory macrophages before and during the
      inflammatory response of the virgin bovine mammary gland.
AB  - BACKGROUND: Macrophages may play a prominent role in defense of the bovine
      mammary gland, and their functionality is necessary for successful eradication of
      bacterial pathogens. In contrast to necrosis, however, apoptosis has not yet been
      studied in macrophages from bovine mammary glands. Therefore, the aim of this
      study was to confirm the occurrence of apoptosis in macrophages from resting
      heifer mammary glands and during the inflammatory response. METHODS: Inflammatory
      response was induced by phosphate buffered saline (PBS) and by lipopolysaccharide
      (LPS). Resident macrophages (RESMAC) were obtained before and inflammatory
      macrophages (INFMAC) 24, 48, 72 and 168 hours after inducing inflammatory
      response in mammary glands of unbred heifers. Cell samples were analyzed for
      differential counts, apoptosis and necrosis using flow cytometry. RESULTS:
      Populations of RESMAC and INFMAC contained monocyte-like cells and vacuolized
      cells. Apoptosis was detected differentially in both morphologically different
      types of RESMAC and INFMAC and also during initiation and resolution of the
      inflammatory response. In the RESMAC population, approximately one-tenth of
      monocyte-like cells and one-third of vacuolized cells were apoptotic. In the
      INFMAC population obtained 24 h after PBS treatment, approximately one-tenth of
      monocyte-like cells and almost one-quarter of vacuolized cells were apoptotic. At
      the same time following LPS, however, we observed a significantly lower
      percentage of apoptotic cells in the population of monocyte-like INFMAC and
      vacuolized INFMAC. Moreover, a higher percentage of apoptotic cells in INFMAC was
      detected during all time points after PBS in contrast to LPS. Comparing RESMAC
      and INFMAC, we observed that vacuolized cells from populations of RESMAC and
      INFMAC underwent apoptosis more intensively than did monocyte-like cells.
      CONCLUSIONS: We conclude that apoptosis of virgin mammary gland macrophages is
      involved in regulating their lifespan, and it is involved in the resolution
      process of the inflammatory response.

PMID- 20144207
TI  - Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic
      inflammation in allergic rhinitis.
AB  - BACKGROUND: The CC-chemokine receptor-3 (CCR3) has emerged as a target molecule
      for pharmacological intervention in allergic inflammation. OBJECTIVE: To examine
      whether a dual CCR3 and H1-receptor antagonist (AZD3778) affects allergic
      inflammation and symptoms in allergic rhinitis. METHODS: Patients with seasonal
      allergic rhinitis were subjected to three seven days' allergen challenge series.
      Treatment with AZD3778 was given in a placebo and antihistamine-controlled
      design. Symptoms and nasal peak inspiratory flow (PIF) were monitored in the
      morning, ten minutes post challenge, and in the evening. Nasal lavages were
      carried out at the end of each challenge series and alpha2-macroglobulin, ECP,
      and tryptase were monitored as indices of allergic inflammation. RESULTS: Plasma
      levels of AZD3778 were stable throughout the treatment series. AZD3778 and the
      antihistamine (loratadine) reduced rhinitis symptoms recorded ten minutes post
      challenge during this period. AZD3778, but not the anti-histamine, also improved
      nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening
      nasal symptoms from the last five days of the allergen challenge series showed
      statistically significant reductions for AZD3778, but not for loratadine. ECP was
      reduced by AZD3778, but not by loratadine. CONCLUSIONS: AZD3778 exerts anti
      eosinophil and symptom-reducing effects in allergic rhinitis and part of this
      effect can likely be attributed to CCR3-antagonism. The present data are of
      interest with regard to the potential use of AZD3778 in allergic rhinitis and to
      the relative importance of eosinophil actions to the symptomatology of allergic
      rhinitis. TRIAL REGISTRATION: EudraCT No: 2005-002805-21.

PMID- 20144208
TI  - A worldwide correlation of lactase persistence phenotype and genotypes.
AB  - BACKGROUND: The ability of adult humans to digest the milk sugar lactose -
      lactase persistence - is a dominant Mendelian trait that has been a subject of
      extensive genetic, medical and evolutionary research. Lactase persistence is
      common in people of European ancestry as well as some African, Middle Eastern and
      Southern Asian groups, but is rare or absent elsewhere in the world. The recent
      identification of independent nucleotide changes that are strongly associated
      with lactase persistence in different populations worldwide has led to the
      possibility of genetic tests for the trait. However, it is highly unlikely that
      all lactase persistence-associated variants are known. Using an extensive
      database of lactase persistence phenotype frequencies, together with information
      on how those data were collected and data on the frequencies of lactase
      persistence variants, we present a global summary of the extent to which current
      genetic knowledge can explain lactase persistence phenotype frequency. RESULTS:
      We used surface interpolation of Old World lactase persistence genotype and
      phenotype frequency estimates obtained from all available literature and perform
      a comparison between predicted and observed trait frequencies in continuous
      space. By accommodating additional data on sample numbers and known false
      negative and false positive rates for the various lactase persistence phenotype
      tests (blood glucose and breath hydrogen), we also apply a Monte Carlo method to
      estimate the probability that known lactase persistence-associated allele
      frequencies can explain observed trait frequencies in different regions.
      CONCLUSION: Lactase persistence genotype data is currently insufficient to
      explain lactase persistence phenotype frequency in much of western and southern
      Africa, southeastern Europe, the Middle East and parts of central and southern
      Asia. We suggest that further studies of genetic variation in these regions
      should reveal additional nucleotide variants that are associated with lactase
      persistence.

PMID- 20144209
TI  - An effective approach for identification of in vivo protein-DNA binding sites
      from paired-end ChIP-Seq data.
AB  - BACKGROUND: ChIP-Seq, which combines chromatin immunoprecipitation (ChIP) with
      high-throughput massively parallel sequencing, is increasingly being used for
      identification of protein-DNA interactions in vivo in the genome. However, to
      maximize the effectiveness of data analysis of such sequences requires the
      development of new algorithms that are able to accurately predict DNA-protein
      binding sites. RESULTS: Here, we present SIPeS (Site Identification from Paired
      end Sequencing), a novel algorithm for precise identification of binding sites
      from short reads generated by paired-end solexa ChIP-Seq technology. In this
      paper we used ChIP-Seq data from the Arabidopsis basic helix-loop-helix
      transcription factor ABORTED MICROSPORES (AMS), which is expressed within the
      anther during pollen development, the results show that SIPeS has better
      resolution for binding site identification compared to two existing ChIP-Seq peak
      detection algorithms, Cisgenome and MACS. CONCLUSIONS: When compared to Cisgenome
      and MACS, SIPeS shows better resolution for binding site discovery. Moreover,
      SIPeS is designed to calculate the mappable genome length accurately with the
      fragment length based on the paired-end reads. Dynamic baselines are also
      employed to effectively discriminate closely adjacent binding sites, for
      effective binding sites discovery, which is of particular value when working with
      high-density genomes.

PMID- 20144211
TI  - Effect of chronic treatment with Rosiglitazone on Leydig cell steroidogenesis in
      rats: in vivo and ex vivo studies.
AB  - BACKGROUND: The present study was designed to examine the effect of chronic
      treatment with rosiglitazone - thiazolidinedione used in the treatment of type 2
      diabetes mellitus for its insulin sensitizing effects - on the Leydig cell
      steroidogenic capacity and expression of the steroidogenic acute regulatory
      protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc) in normal
      adult rats. METHODS: Twelve adult male Wistar rats were treated with
      rosiglitazone (5 mg/kg) administered by gavage for 15 days. Twelve control
      animals were treated with the vehicle. The ability of rosiglitazone to directly
      affect the production of testosterone by Leydig cells ex vivo was evaluated using
      isolated Leydig cells from rosiglitazone-treated rats. Testosterone production
      was induced either by activators of the cAMP/PKA pathway (hCG and dbcAMP) or
      substrates of steroidogenesis [22(R)-hydroxy-cholesterol (22(R)-OH-C), which is a
      substrate for the P450scc enzyme, and pregnenolone, which is the product of the
      P450scc-catalyzed step]. Testosterone in plasma and in incubation medium was
      measured by radioimmunoassay. The StAR and P450scc expression was detected by
      immunocytochemistry. RESULTS: The levels of total circulating testosterone were
      not altered by rosiglitazone treatment. A decrease in basal or induced
      testosterone production occurred in the Leydig cells of rosiglitazone-treated
      rats. The ultrastructural and immunocytochemical analysis of Leydig cells from
      rosiglitazone-treated rats revealed cells with characteristics of increased
      activity as well as increased StAR and P450scc expression, which are key proteins
      in androgen biosynthesis. However, a number of rosiglitazone-treated cells
      exhibited significant mitochondrial damage. CONCLUSION: The results revealed that
      the Leydig cells from rosiglitazone-treated rats showed significant reduction in
      testosterone production under basal, hCG/dbcAMP- or 22 (R)-OH-C/pregnenolone
      induced conditions, although increased labeling of StAR and P450scc was detected
      in these cells by immunocytochemistry. The ultrastructural study suggested that
      the lower levels of testosterone produced by these cells could be due to
      mitochondrial damage induced by rosiglitazone.

PMID- 20144210
TI  - Growth factor concentrations and their placental mRNA expression are modulated in
      gestational diabetes mellitus: possible interactions with macrosomia.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is a form of diabetes that occurs
      during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed
      macrosomia which is influenced by maternal hypergycemia and endocrine status
      through placental circulation. The study was undertaken to investigate the
      implication of growth factors and their receptors in GDM and macrosomia, and to
      discuss the role of the materno-foeto-placental axis in the in-utero regulation
      of foetal growth. METHODS: 30 women with GDM and their 30 macrosomic babies (4.75
      +/- 0.15 kg), and 30 healthy age-matched pregnant women and their 30 newborns
      (3.50 +/- 0.10 kg) were recruited in the present study. Serum concentrations of
      GH and growth factors, i.e., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were
      determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF
      2, PDGF-B and EGF, and their receptors, i.e., GHR, IGF-IR, FGF-2R, EGFR and PDGFR
      beta were quantified by using RT-qPCR. RESULTS: The serum concentrations of IGF
      I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic
      babies as compared to their respective controls. The placental mRNA expression of
      the growth factors was either upregulated (FGF-2 or PDGF-B) or remained unaltered
      (IGF-I and EGF) in the placenta of GDM women. The mRNA expression of three growth
      factor receptors, i.e., IGF-IR, EGFR and PDGFR-beta, was upregulated in the
      placenta of GDM women. Interestingly, serum concentrations of GH were
      downregulated in the GDM women and their macrosomic offspring. Besides, the
      expression of mRNAs encoding for GHR was higher, but that encoding for GH was
      lower, in the placenta of GDM women than control women. CONCLUSIONS: Our results
      demonstrate that growth factors might be implicated in GDM and, in part, in the
      pathology of macrosomia via materno-foeto-placental axis.

PMID- 20144212
TI  - Are we doing enough? Evaluation of the Polio Eradication Initiative in a district
      of Pakistan's Punjab province: a LQAS study.
AB  - BACKGROUND: The success of the Global Polio Eradication Initiative was
      remarkable, but four countries - Afghanistan, Pakistan, India and Nigeria - never
      interrupted polio transmission. Pakistan reportedly achieved all milestones
      except interrupting virus transmission. The aim of the study was to establish
      valid and reliable estimate for: routine oral polio vaccine (OPV) coverage,
      logistics management and the quality of monitoring systems in health facilities,
      NIDs OPV coverage, the quality of NIDs service delivery in static centers and
      mobile teams, and to ultimately provide scientific evidence for tailoring future
      interventions. METHODS: A cross-sectional study using lot quality assessment
      sampling was conducted in the District Nankana Sahib of Pakistan's Punjab
      province. Twenty primary health centers and their catchment areas were selected
      randomly as 'lots'. The study involved the evaluation of 1080 children aged 12-23
      months for routine OPV coverage, 20 health centers for logistics management and
      quality of monitoring systems, 420 households for NIDs OPV coverage, 20 static
      centers and 20 mobile teams for quality of NIDs service delivery. Study
      instruments were designed according to WHO guidelines. RESULTS: Five out of
      twenty lots were rejected for unacceptably low routine immunization coverage. The
      validity of coverage was questionable to extent that all lots were rejected.
      Among the 54.1% who were able to present immunization cards, only 74.0% had valid
      immunization. Routine coverage was significantly associated with card
      availability and socioeconomic factors. The main reasons for routine immunization
      failure were absence of a vaccinator and unawareness of need for immunization.
      Health workers (96.9%) were a major source of information. All of the 20 lots
      were rejected for poor compliance in logistics management and quality of
      monitoring systems. Mean compliance score and compliance percentage for logistics
      management were 5.4 +/- 2.0 (scale 0-9) and 59.4% while those for quality of
      monitoring systems were 3.3 +/- 1.2 (scale 0-6) and 54.2%. The 15 out of 20 lots
      were rejected for unacceptably low NIDs coverage by finger-mark. All of the 20
      lots were rejected for poor NIDs service delivery (mean compliance score = 11.7
      +/- 2.1 [scale 0-16]; compliance percentage = 72.8%). CONCLUSION: Low coverage,
      both routine and during NIDs, and poor quality of logistics management,
      monitoring systems and NIDs service delivery were highlighted as major
      constraints in polio eradication and these should be considered in prioritizing
      future strategies.

PMID- 20144214
TI  - Minimizing the source of nociception and its concurrent effect on sensory
      hypersensitivity: an exploratory study in chronic whiplash patients.
AB  - BACKGROUND: The cervical zygapophyseal joints may be a primary source of pain in
      up to 60% of individuals with chronic whiplash associated disorders (WAD) and may
      be a contributing factor for peripheral and centrally mediated pain (sensory
      hypersensitivity). Sensory hypersensitivity has been associated with a poor
      prognosis. The purpose of the study was to determine if there is a change in
      measures indicative of sensory hypersensitivity in patients with chronic WAD
      grade II following a medial branch block (MBB) procedure in the cervical spine.
      METHODS: Measures of sensory hypersensitivity were taken via quantitative sensory
      testing (QST) consisting of pressure pain thresholds (PPT's) and cold pain
      thresholds (CPT's). In patients with chronic WAD (n = 18), the measures were
      taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at
      remote sites have been considered an indicator of central hypersensitivity. A
      healthy age and gender matched comparison group (n = 18) was measured at
      baseline. An independent t-test was applied to determine if there were any
      significant differences between the WAD and normative comparison groups at
      baseline with respect to cold pain and pressure pain thresholds. A dependent t
      test was used to determine whether there were any significant differences between
      the pre and post intervention cold pain and pressure pain thresholds in the
      patients with chronic WAD. RESULTS: At baseline, PPT's were decreased at all
      three sites in the WAD group (p < 0.001). Cold pain thresholds were increased in
      the cervical spine in the WAD group (p < 0.001). Post-MBB, the WAD group showed
      significant increases in PPT's at all sites (p < 0.05), and significant decreases
      in CPT's at the cervical spine (p < 0.001). CONCLUSIONS: The patients with
      chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical
      and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity
      following a decrease in their primary source of pain stemming from the cervical
      zygapophyseal joints.

PMID- 20144213
TI  - Regulation of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase
      activating protein/5-lipoxygenase by 4-hydroxynonenal in human osteoarthritic
      chondrocytes.
AB  - INTRODUCTION: This study aimed to investigate whether hydroxynonenal (HNE)
      depletion is responsible for the switch from cyclooxygenase-2 (COX-2) and
      microsomal prostaglandin E2 synthase-1 (mPGES-1) to 5-lipoxygenase-activating
      protein (FLAP) and 5-lipoxygenase (5-LOX). METHODS: For COX-2 and mPGES-1
      studies, human osteoarthritic chondrocytes were stimulated at different
      incubation times (up to 24 hours) with a single or repetitive addition of 10 muM
      HNE to the cultures at 2-hour intervals, up to 14 hours. For 5-LOX and FLAP
      studies, cells were treated with a single addition of 10 muM HNE for 24 hours, 48
      hours, and 72 hours in the presence or absence of naproxen (a nonspecific COX-2
      inhibitor) or antibody anti-transforming growth factor-beta 1 (TGF-beta1). The
      protein levels of COX-2, mPGES-1 and early growth response factor-1 (Egr-1)
      transcription factor were evaluated by western blot, and those of prostaglandin
      E2 (PGE2), leukotriene B4 (LTB4) and TGF-beta1 were determined with commercial
      kits. The levels of mPGES-1, FLAP and 5-LOX mRNA were measured by real-time RT
      PCR. Transient transfection was performed to determine promoter activities of
      mPGES-1 and 5-LOX. RESULTS: Single addition of 10 muM HNE to cultured
      chondrocytes induced PGE2 release as well as COX-2 and mPGES-1 expression at the
      protein and mRNA levels, with a plateau reached respectively at 8 and 16 hours of
      incubation, followed by a subsequent decline. However, repeated treatments with
      HNE prevented the decline of COX-2 and mPGES-1 expression that occurred with a
      single aldehyde addition. HNE induced mPGES-1 promoter activity, possibly through
      transcription factor Egr-1 activation. After 48 hours, when COX-2 expression
      decreased, the LTB4 level rose through 5-LOX and FLAP upregulation. The addition
      of naproxen to cultured chondrocytes revealed that FLAP and 5-LOX regulation by
      HNE required PGE2 production. Furthermore, our data showed that HNE significantly
      induced TGF-beta1 production. The addition of anti-TGF-beta1 antibody reduced HNE
      induced 5-LOX and FLAP expression by 40%, indicating the partial involvement of a
      TGF-beta1-dependent mechanism. CONCLUSIONS: Our data demonstrate that the shunt
      to the FLAP and 5-LOX pathway in HNE-induced human osteoarthritic chondrocytes is
      attributed to COX-2 and mPGES-1 inhibition, probably due to HNE depletion. PGE2
      and TGF-beta1 are suggested to be involved in this regulation.

PMID- 20144215
TI  - Warburg effect in chemosensitivity: targeting lactate dehydrogenase-A re
      sensitizes taxol-resistant cancer cells to taxol.
AB  - BACKGROUND: Taxol is one of the most effective chemotherapeutic agents for the
      treatment of patients with breast cancer. Despite impressive clinical responses
      initially, the majority of patients eventually develop resistance to Taxol.
      Lactate dehydrogenase-A (LDH-A) is one of the predominant isoforms of LDH
      expressed in breast tissue, which controls the conversion of pyruvate to lactate
      and plays an important role in glucose metabolism. In this study we investigated
      the role of LDH-A in mediating Taxol resistance in human breast cancer cells.
      RESULTS: Taxol-resistant subclones, derived from the cancer cell line MDA-MB-435,
      sustained continuous growth in high concentrations of Taxol while the Taxol
      sensitive cells could not. The increased expression and activity of LDH-A were
      detected in Taxol-resistant cells when compared with their parental cells. The
      downregulation of LDH-A by siRNA significantly increased the sensitivity of Taxol
      resistant cells to Taxol. A higher sensitivity to the specific LDH inhibitor,
      oxamate, was found in the Taxol-resistant cells. Furthermore, treating cells with
      the combination of Taxol and oxamate showed a synergistical inhibitory effect on
      Taxol-resistant breast cancer cells by promoting apoptosis in these cells.
      CONCLUSION: LDH-A plays an important role in Taxol resistance and inhibition of
      LDH-A re-sensitizes Taxol-resistant cells to Taxol. This supports that Warburg
      effect is a property of Taxol resistant cancer cells and may play an important
      role in the development of Taxol resistance. To our knowledge, this is the first
      report showing that the increased expression of LDH-A plays an important role in
      Taxol resistance of human breast cancer cells. This study provides valuable
      information for the future development and use of targeted therapies, such as
      oxamate, for the treatment of patients with Taxol-resistant breast cancer.

PMID- 20144216
TI  - A new therapeutic strategy for lung tissue injury induced by influenza with CR2
      targeting complement inhibitor.
AB  - BACKGROUND: Influenza is a respiratory disease that seriously threatens human
      health. In fact, influenza virus itself does not make critical contribution to
      mortality induced by influenza, but "cytokine storm" produced by the excessive
      immune response triggered by the virus can result in inflammatory reaction of
      lung tissues and fatal lung tissue injury, and thus increase influenza mortality.
      Therefore, besides antiviral drugs, immunosuppression drugs should also be
      included in infection treatment. PRESENTATION OF THE HYPOTHESIS: Complement is
      the center of inflammatory reaction. If complement system is over activated, the
      body will have strong inflammatory reaction or tissue injury, resulting in
      pathological process. Many studies have proved that, inflammatory injury of lung
      tissues caused by influenza virus is closely related to complement activation.
      Therefore, inhibiting complement activation can significantly reduce inflammatory
      injury in lung tissues. As complement is both a physiological defense and
      pathological damage medium, systematic inhibition may result in side effects
      including infection. Therefore, we design targeting complement inhibitors for
      complement activation sites, i.e. with CR2 as targeting vector, complement
      inhibitors like CD59 and Crry are targeted to inflammatory sites to specially
      inhibit the complement activation in local injury, thus local inflammatory
      reaction is inhibited. TESTING THE HYPOTHESIS: CR2-CD59 and CR2-Crry targeting
      complement inhibitors are fusion-expressed, and their biological activity is
      examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are
      used to treat mouse influenza viral pneumonia model, with PBS treatment group as
      the control. The survival and lung tissue injury of the mice is observed and the
      effect of CR2 targeting complement inhibitors on pneumonia induced by influenza
      virus is evaluated. IMPLICATIONS OF THE HYPOTHESIS: CR2 targeting complement
      inhibitors are expected to be ideal drugs for viral pneumonia.

PMID- 20144217
TI  - Stone formation in peach fruit exhibits spatial coordination of the lignin and
      flavonoid pathways and similarity to Arabidopsis dehiscence.
AB  - BACKGROUND: Lignification of the fruit endocarp layer occurs in many angiosperms
      and plays a critical role in seed protection and dispersal. This process has been
      extensively studied with relationship to pod shatter or dehiscence in
      Arabidopsis. Dehiscence is controlled by a set of transcription factors that
      define the fruit tissue layers and whether or not they lignify. In contrast,
      relatively little is known about similar processes in other plants such as stone
      fruits which contain an extremely hard lignified endocarp or stone surrounding a
      single seed. RESULTS: Here we show that lignin deposition in peach initiates near
      the blossom end within the endocarp layer and proceeds in a distinct spatial
      temporal pattern. Microarray studies using a developmental series from young
      fruits identified a sharp and transient induction of phenylpropanoid, lignin and
      flavonoid pathway genes concurrent with lignification and subsequent stone
      hardening. Quantitative polymerase chain reaction studies revealed that specific
      phenylpropanoid (phenylalanine ammonia-lyase and cinnamate 4-hydroxylase) and
      lignin (caffeoyl-CoA O-methyltransferase, peroxidase and laccase) pathway genes
      were induced in the endocarp layer over a 10 day time period, while two lignin
      genes (p-coumarate 3-hydroxylase and cinnamoyl CoA reductase) were co-regulated
      with flavonoid pathway genes (chalcone synthase, dihydroflavanol 4-reductase,
      leucoanthocyanidin dioxygen-ase and flavanone-3-hydrosylase) which were mesocarp
      and exocarp specific. Analysis of other fruit development expression studies
      revealed that flavonoid pathway induction is conserved in the related Rosaceae
      species apple while lignin pathway induction is not. The transcription factor
      expression of peach genes homologous to known endocarp determinant genes in
      Arabidopsis including SHATTERPROOF, SEEDSTCK and NAC SECONDARY WALL THICENING
      PROMOTING FACTOR 1 were found to be specifically expressed in the endocarp while
      the negative regulator FRUITFUL predominated in exocarp and mesocarp.
      CONCLUSIONS: Collectively, the data suggests, first, that the process of endocarp
      determination and differentiation in peach and Arabidopsis share common
      regulators and, secondly, reveals a previously unknown coordination of competing
      lignin and flavonoid biosynthetic pathways during early fruit development.

PMID- 20144218
TI  - Development and Evaluation of a Psychosocial Intervention for Children and
      Teenagers Experiencing Diabetes (DEPICTED): a protocol for a cluster randomised
      controlled trial of the effectiveness of a communication skills training
      programme for healthcare professionals working with young people with type 1
      diabetes.
AB  - BACKGROUND: Diabetes is the third most common chronic condition in childhood and
      poor glycaemic control leads to serious short-term and life-limiting long-term
      complications. In addition to optimal medical management, it is widely recognised
      that psychosocial and educational factors play a key role in improving outcomes
      for young people with diabetes. Recent systematic reviews of psycho-educational
      interventions recognise the need for new methods to be developed in consultation
      with key stakeholders including patients, their families and the
      multidisciplinary diabetes healthcare team. METHODS/DESIGN: Following a
      development phase involving key stakeholders, a psychosocial intervention for use
      by paediatric diabetes staff and not requiring input from trained psychologists
      has been developed, incorporating a communication skills training programme for
      health professionals and a shared agenda-setting tool. The effectiveness of the
      intervention will be evaluated in a cluster-randomised controlled trial (RCT).
      The primary outcome, to be measured in children aged 4-15 years diagnosed with
      type 1 diabetes for at least one year, is the effect on glycaemic control (HbA1c)
      during the year after training of the healthcare team is completed. Secondary
      outcomes include quality of life for patients and carers and cost-effectiveness.
      Patient and carer preferences for service delivery will also be assessed. Twenty
      six paediatric diabetes teams are participating in the trial, recruiting a total
      of 700 patients for evaluation of outcome measures. Half the participating teams
      will be randomised to receive the intervention at the beginning of the trial and
      remaining centres offered the training package at the end of the one year trial
      period. DISCUSSION: The primary aim of the trial is to determine whether a
      communication skills training intervention for specialist paediatric diabetes
      teams will improve clinical and psychological outcomes for young people with type
      1 diabetes. Previous research indicates the effectiveness of specialist
      psychological interventions in achieving sustained improvements in glycaemic
      control. This trial will evaluate an intervention which does not require the
      involvement of trained psychologists, maximising the potential feasibility of
      delivery in a wider NHS context. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN61568050.

PMID- 20144220
TI  - Computational prediction and experimental validation of evolutionarily conserved
      microRNA target genes in bilaterian animals.
AB  - BACKGROUND: In many eukaryotes, microRNAs (miRNAs) bind to complementary sites in
      the 3'-untranslated regions (3'-UTRs) of target messenger RNAs (mRNAs) and
      regulate their expression at the stage of translation. Recent studies have
      revealed that many miRNAs are evolutionarily conserved; however, the evolution of
      their target genes has yet to be systematically characterized. We sought to
      elucidate a set of conserved miRNA/target-gene pairs and to analyse the mechanism
      underlying miRNA-mediated gene regulation in the early stage of bilaterian
      evolution. RESULTS: Initially, we extracted five evolutionarily conserved miRNAs
      (let-7, miR-1, miR-124, miR-125/lin-4, and miR-34) among five diverse bilaterian
      animals. Subsequently, we designed a procedure to predict evolutionarily
      conserved miRNA/target-gene pairs by introducing orthologous gene information. As
      a result, we extracted 31 orthologous miRNA/target-gene pairs that were conserved
      among at least four diverse bilaterian animals; the prediction set showed
      prominent enrichment of orthologous miRNA/target-gene pairs that were verified
      experimentally. Approximately 84% of the target genes were regulated by three
      miRNAs (let-7, miR-1, and miR-124) and their function was classified mainly into
      the following categories: development, muscle formation, cell adhesion, and gene
      regulation. We used a reporter gene assay to experimentally verify the
      downregulation of six candidate pairs (out of six tested pairs) in HeLa cells.
      CONCLUSIONS: The application of our new method enables the identification of 31
      miRNA/target-gene pairs that were expected to have been regulated from the era of
      the common bilaterian ancestor. The downregulation of all six candidate pairs
      suggests that orthologous information contributed to the elucidation of the
      primordial set of genes that has been regulated by miRNAs; it was also an
      efficient tool for the elimination of false positives from the predicted
      candidates. In conclusion, our study identified potentially important miRNA
      target pairs that were evolutionarily conserved throughout diverse bilaterian
      animals and that may provide new insights into early-stage miRNA functions.

PMID- 20144221
TI  - Mammographic density and markers of socioeconomic status: a cross-sectional
      study.
AB  - BACKGROUND: Socioeconomic status (SES) is known to be positively associated with
      breast cancer risk but its relationship with mammographic density, a marker of
      susceptibility to breast cancer, is unclear. This study aims to investigate
      whether mammographic density varies by SES and to identify the underlying
      anthropometric, lifestyle and reproductive factors leading to such variation.
      METHODS: In a cross-sectional study of mammographic density in 487 pre-menopausal
      women, SES was assessed from questionnaire data using highest achieved level of
      formal education, quintiles of Census-derived Townsend scores and urban/rural
      classification of place of residence. Mammographic density was measured on
      digitised films using a computer-assisted method. Linear regression models were
      fitted to assess the association between SES variables and mammographic density,
      adjusting for correlated variables. RESULTS: In unadjusted models, percent
      density was positively associated with SES, with an absolute difference in
      percent density of 6.3% (95% CI 1.6%, 10.5%) between highest and lowest
      educational categories, and of 6.6% (95% CI -0.7%, 12.9%) between highest and
      lowest Townsend quintiles. These associations were mainly driven by strong
      negative associations between these SES variables and lucent area and were
      attenuated upon adjustment for body mass index (BMI). There was little evidence
      that reproductive factors explained this association. SES was not associated with
      the amount of dense tissue in the breast before or after BMI adjustment. The
      effect of education on percent density persisted after adjustment for Townsend
      score. Mammographic measures did not vary according to urban/rural place of
      residence. CONCLUSIONS: The observed SES gradients in percent density paralleled
      known SES gradients in breast cancer risk. Although consistent with the
      hypothesis that percent density may be a mediator of the SES differentials in
      breast cancer risk, the SES gradients in percent density were mainly driven by
      the negative association between SES and BMI. Nevertheless, as density affects
      the sensitivity of screen-film mammography, the higher percent density found
      among high SES women would imply that these women have a higher risk of
      developing cancer but a lower likelihood of having it detected earlier.

PMID- 20144222
TI  - 2x genomes--depth does matter.
AB  - BACKGROUND: Given the availability of full genome sequences, mapping gene gains,
      duplications, and losses during evolution should theoretically be
      straightforward. However, this endeavor suffers from overemphasis on detecting
      conserved genome features, which in turn has led to sequencing multiple eutherian
      genomes with low coverage rather than fewer genomes with high-coverage and more
      even distribution in the phylogeny. Although limitations associated with analysis
      of low coverage genomes are recognized, they have not been quantified. RESULTS:
      Here, using recently developed comparative genomic application systems, we
      evaluate the impact of low-coverage genomes on inferences pertaining to gene
      gains and losses when analyzing eukaryote genome evolution through gene
      duplication. We demonstrate that, when performing inference of genome content
      evolution, low-coverage genomes generate not only a massive number of false gene
      losses, but also striking artifacts in gene duplication inference, especially at
      the most recent common ancestor of low-coverage genomes. We show that the
      artifactual gains are caused by the low coverage of genome sequence per se rather
      than by the increased taxon sampling in a biased portion of the species tree.
      CONCLUSIONS: We argue that it will remain difficult to differentiate artifacts
      from true changes in modes and tempo of genome evolution until there is better
      homogeneity in both taxon sampling and high-coverage sequencing. This is
      important for broadening the utility of full genome data to the community of
      evolutionary biologists, whose interests go well beyond widely conserved
      physiologies and developmental patterns as they seek to understand the generative
      mechanisms underlying biological diversity.

PMID- 20144219
TI  - Sepsis biomarkers: a review.
AB  - INTRODUCTION: Biomarkers can be useful for identifying or ruling out sepsis,
      identifying patients who may benefit from specific therapies or assessing the
      response to therapy. METHODS: We used an electronic search of the PubMed database
      using the key words "sepsis" and "biomarker" to identify clinical and
      experimental studies which evaluated a biomarker in sepsis. RESULTS: The search
      retrieved 3370 references covering 178 different biomarkers. CONCLUSIONS: Many
      biomarkers have been evaluated for use in sepsis. Most of the biomarkers had been
      tested clinically, primarily as prognostic markers in sepsis; relatively few have
      been used for diagnosis. None has sufficient specificity or sensitivity to be
      routinely employed in clinical practice. PCT and CRP have been most widely used,
      but even these have limited ability to distinguish sepsis from other inflammatory
      conditions or to predict outcome.

PMID- 20144223
TI  - Dynamic probe selection for studying microbial transcriptome with high-density
      genomic tiling microarrays.
AB  - BACKGROUND: Current commercial high-density oligonucleotide microarrays can hold
      millions of probe spots on a single microscopic glass slide and are ideal for
      studying the transcriptome of microbial genomes using a tiling probe design. This
      paper describes a comprehensive computational pipeline implemented specifically
      for designing tiling probe sets to study microbial transcriptome profiles.
      RESULTS: The pipeline identifies every possible probe sequence from both forward
      and reverse-complement strands of all DNA sequences in the target genome
      including circular or linear chromosomes and plasmids. Final probe sequence
      lengths are adjusted based on the maximal oligonucleotide synthesis cycles and
      best isothermality allowed. Optimal probes are then selected in two stages -
      sequential and gap-filling. In the sequential stage, probes are selected from
      sequence windows tiled alongside the genome. In the gap-filling stage, additional
      probes are selected from the largest gaps between adjacent probes that have
      already been selected, until a predefined number of probes is reached. Selection
      of the highest quality probe within each window and gap is based on five
      criteria: sequence uniqueness, probe self-annealing, melting temperature,
      oligonucleotide length, and probe position. CONCLUSIONS: The probe selection
      pipeline evaluates global and local probe sequence properties and selects a set
      of probes dynamically and evenly distributed along the target genome. Unique to
      other similar methods, an exact number of non-redundant probes can be designed to
      utilize all the available probe spots on any chosen microarray platform. The
      pipeline can be applied to microbial genomes when designing high-density tiling
      arrays for comparative genomics, ChIP chip, gene expression and comprehensive
      transcriptome studies.

PMID- 20144224
TI  - Newly diagnosed exudative age-related macular degeneration treated with
      pegaptanib sodium monotherapy in US community-based practices: medical chart
      review study.
AB  - BACKGROUND: Studies have shown that early detection and treatment of neovascular
      age-related macular degeneration (NV-AMD) can delay vision loss and blindness.
      The objective of this study was to evaluate the efficacy/safety of intravitreal
      pegaptanib sodium monotherapy in treatment-naive subjects with newly diagnosed NV
      AMD and to gain insight into characteristics of lesions treated in community
      based practices. METHODS: From seven private US practices, charts were
      retrospectively reviewed on 73 subjects with previously untreated subfoveal
      choroidal NV-AMD treated with their first dose of pegaptanib monotherapy on/after
      4/1/2005 through 6/5/2006, receiving > or =4 treatments at 6-week intervals over
      21 weeks. Primary endpoint: mean visual acuity (VA) change from baseline to month
      6. RESULTS: 75% of lesions were occult, and 82% were subfoveal. From baseline to
      month 6, mean VA change was -0.68 lines; 58% and 16% gained > or =0 and > or =3
      lines of VA, and 70% were responders (<3 lines lost). In 35 subjects with early
      disease, 80% were responders with a mean gain of 0.46 lines. CONCLUSION:
      Pegaptanib is effective in real-world patients with treatment-naive NV-AMD in
      uncontrolled community-based retina practices.

PMID- 20144225
TI  - Homopolymeric tracts represent a general regulatory mechanism in prokaryotes.
AB  - BACKGROUND: While, traditionally, regulation of gene expression can be grouped
      into transcriptional, translational, and post-translational mechanisms, some
      mechanisms of rapid genetic variation can also contribute to regulation of gene
      expression, e.g., phase variation. RESULTS: We show here that prokaryotes evolved
      to include homopolymeric tracts (HTs) within coding genes as a system that allows
      for efficient gene inactivation. Analyses of 81 bacterial and 18 archaeal genomes
      showed that poly(A) and poly(T) HTs are overrepresented in these genomes and
      preferentially located at the 5' end of coding genes. Location of HTs at the 5'
      end is not driven by a preferential placement of aminoacids encoded by the AAA
      and TTT codons at the N-terminal of proteins. The inlA gene of the pathogen L.
      monocytogenes was used as a model to further study the role of HTs in reversible
      gene inactivation. In a number of L. monocytogenes strains, inlA harbors a 5'
      poly(A) HT, which regularly shows frameshift mutation leading to expression of a
      truncated 8 aa InlA protein. Translational fusions of the inlA 5' end allowed us
      to estimate that the frequency of variation in this HT is about 1,000 fold higher
      than the estimated average point mutation frequency. CONCLUSIONS: As frameshift
      mutations in HTs can occur at high frequencies and enable efficient gene
      inactivation, hypermutable HTs appear to represent a universal system for
      regulation of gene expression in prokaryotes. Combined with other studies
      indicating that HTs also enable rapid diversification of both coding and
      regulatory genetic sequences in eukaryotes, our data suggest that hypermutable
      HTs represent a general and rapid evolutionary mechanism facilitating adaptation
      and gene regulation across diverse organisms.

PMID- 20144226
TI  - A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of
      postmenopausal breast cancer patients with poor response to neoadjuvant
      letrozole.
AB  - BACKGROUND: Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in
      CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition
      of aromatase with letrozole constitutes the best option for treating estrogen
      dependent BC in postmenopausal women. We evaluate a series of polymorphisms of
      CYP19A1 and their effect on response to neoadjuvant letrozole in early BC.
      METHODS: We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR
      [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by
      radiology at 4th month by World Health Organization (WHO) criteria. Three
      polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region
      (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood.
      RESULTS: Thirty-five women (36.8%) achieved a radiological response to letrozole.
      The histopathological and immunohistochemical parameters, including hormonal
      receptor status, were not associated with the response to letrozole. Only the
      genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor
      response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a
      progression of the disease. Those patients carrying the genetic variants (AC/AA)
      of rs4646 presented a lower progression-free survival than the patients
      homozygous for the reference variant (p = 0.0686). This effect was especially
      significant in the group of elderly patients not operated after letrozole
      induction (p = 0.009). CONCLUSIONS: Our study reveals that the rs4646
      polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with
      poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646
      polymorphism could be a useful tool in order to orientate the treatment in
      elderly BC patients.

PMID- 20144227
TI  - Analysis of gene expression in response to water deficit of chickpea (Cicer
      arietinum L.) varieties differing in drought tolerance.
AB  - BACKGROUND: Chickpea (C. arietinum L.) ranks third in food legume crop production
      in the world. However, drought poses a serious threat to chickpea production, and
      development of drought-resistant varieties is a necessity. Unfortunately,
      cultivated chickpea has a high morphological but narrow genetic diversity, and
      understanding the genetic processes of this plant is hindered by the fact that
      the chickpea genome has not yet been sequenced and its EST resources are limited.
      In this study, two chickpea varieties having contrasting levels of drought
      tolerance were analyzed for differences in transcript profiling during drought
      stress treatment by withdrawal of irrigation at different time points. Transcript
      profiles of ESTs derived from subtractive cDNA libraries constructed with RNA
      from whole seedlings of both varieties were analyzed at different stages of
      stress treatment. RESULTS: A series of comparisons of transcript abundance
      between two varieties at different time points were made. 319 unique ESTs
      available from different libraries were categorized into eleven clusters
      according to their comparative expression profiles. Expression analysis revealed
      that 70% of the ESTs were more than two fold abundant in the tolerant cultivar at
      any point of the stress treatment of which expression of 33% ESTs were more than
      two fold high even under the control condition. 53 ESTs that displayed very high
      fold relative expression in the tolerant variety were screened for further
      analysis. These ESTs were clustered in four groups according to their expression
      patterns. CONCLUSIONS: Annotation of the highly expressed ESTs in the tolerant
      cultivar predicted that most of them encoded proteins involved in cellular
      organization, protein metabolism, signal transduction, and transcription. Results
      from this study may help in targeting useful genes for improving drought
      tolerance in chickpea.

PMID- 20144228
TI  - Identification of genes associated with growth cessation and bud dormancy
      entrance using a dormancy-incapable tree mutant.
AB  - BACKGROUND: In many tree species the perception of short days (SD) can trigger
      growth cessation, dormancy entrance, and the establishment of a chilling
      requirement for bud break. The molecular mechanisms connecting photoperiod
      perception, growth cessation and dormancy entrance in perennials are not clearly
      understood. The peach [Prunus persica (L.) Batsch] evergrowing (evg) mutant fails
      to cease growth and therefore cannot enter dormancy under SD. We used the evg
      mutant to filter gene expression associated with growth cessation after exposure
      to SD. Wild-type and evg plants were grown under controlled conditions of long
      days (16 h/8 h) followed by transfer to SD (8 h/16 h) for eight weeks. Apical
      tissues were sampled at zero, one, two, four, and eight weeks of SD and
      suppression subtractive hybridization was performed between genotypes at the same
      time points. RESULTS: We identified 23 up-regulated genes in the wild-type with
      respect to the mutant during SD exposure. We used quantitative real-time PCR to
      verify the expression of the differentially expressed genes in wild-type tissues
      following the transition to SD treatment. Three general expression patterns were
      evident: one group of genes decreased at the time of growth cessation (after 2
      weeks in SD), another that increased immediately after the SD exposure and then
      remained steady, and another that increased throughout SD exposure. CONCLUSIONS:
      The use of the dormancy-incapable mutant evg has allowed us to reduce the number
      of genes typically detected by differential display techniques for SD
      experiments. These genes are candidates for involvement in the signalling pathway
      leading from photoperiod perception to growth cessation and dormancy entrance and
      will be the target of future investigations.

PMID- 20144229
TI  - Biochemical characterization of three putative ATPases from a new type IV
      secretion system of Aeromonas veronii plasmid pAC3249A.
AB  - BACKGROUND: Type four secretion systems (TFSS) are bacterial macromolecular
      transport systems responsible for transfer of various substrates such as
      proteins, DNA or protein-DNA complexes. TFSSs encode two or three ATPases
      generating energy for the secretion process. These enzymes exhibit highest
      sequence conservation among type four secretion components. RESULTS: Here, we
      report the biochemical characterization of three ATPases namely TraE, TraJ and
      TraK (VirB4, VirB11 and VirD4 homologs of the Agrobacterium tumefaciens transfer
      system, respectively) from the transfer system of Aeromonas veronii plasmid
      pAC3249A. ATPases were expressed as His-tag fusion proteins in E. coli and
      purified by affinity chromatography. ATP binding and ATP hydrolysis experiments
      were performed with the purified ATPases. TraE and TraK showed strong binding to
      TNP-ATP and TNP-CTP (fluorescent analogs of ATP and CTP respectively) whereas
      TraJ showed weak binding. The optimum temperature range for the three ATPases was
      between 42 degrees C and 50 degrees C. Highest ATP hydrolysis activity for all
      the ATPases was observed in the presence of Mg2+ and Mn2+. However, TraJ and TraK
      also showed activity in the presence of Co2+. TraJ exhibited the highest specific
      activity of all the three ATPases with vmax 118 +/- 5.68 nmol/min/mg protein and
      KM 0.58 +/- 0.10 mM. CONCLUSIONS: This is the first biochemical characterization
      of conjugative transport ATPases encoded by a conjugative plasmid from Aeromonas.
      Our study demonstrated that the three ATPases of a newly reported TFSS of A.
      veronii plasmid pAc3249A are functional in both ATP hydrolysis and ATP binding.

PMID- 20144230
TI  - What physicians want to learn about sickness certification: analyses of
      questionnaire data from 4019 physicians.
AB  - BACKGROUND: Sickness absence is a problem in many Western countries. Physicians
      have an essential role in sickness certification of patients, which is often
      recommended in health care but may have side effects. Despite the potentially
      harming impact of sickness absence, physicians have very limited training in
      insurance medicine, and there is little research on sickness certification
      practices. Our aim was to ascertain what knowledge and skills physicians in
      different clinical settings feel they need in order to improve their competence
      in sickness certification. METHODS: The data for analysis were collected in 2004
      in Stockholm and Ostergotland Counties, Sweden, by use of a comprehensive
      questionnaire about sickness certification issues, which was sent to 7,665
      physicians aged <or= 64 years. The response rate was 71% (n = 5455). Analyses of
      association and factor analysis were applied to the various aspects of competence
      to establish a skills index and a knowledge index, which were used to compare the
      results for physicians in different clinical settings. RESULTS: Most physicians
      stated they needed more knowledge and skills in handling sickness certification,
      e.g. regarding how to assess work capacity (44%) and optimal length and degree of
      sickness absence (50%), and information about aspects of the social insurance
      system (43-63%). Few (20%) reported needing to know more about issuing sickness
      certificates. The index scores varied substantially between different clinical
      settings, and this disparity remained after adjustment for sex, years in
      practice, workplace policy, and support from management. Scores on the skills
      index were significantly higher for physicians in primary care than for those
      working in other areas. CONCLUSIONS: A majority of physicians in most types of
      clinics/practices, not only primary care, indicated the need for more knowledge
      and skills in handling sickness certification cases. Increased knowledge and
      skills are needed in order to protect both the health and equity of patients.
      However, few physicians stated that they needed more skills in filling out
      sickness certificates, which contradicts previous findings about such documents
      being of poor quality and suggests that factors other than mere knowledge and
      skills are involved.

PMID- 20144231
TI  - Molecular risk assessment of BIG 1-98 participants by expression profiling using
      RNA from archival tissue.
AB  - BACKGROUND: The purpose of the work reported here is to test reliable molecular
      profiles using routinely processed formalin-fixed paraffin-embedded (FFPE)
      tissues from participants of the clinical trial BIG 1-98 with a median follow-up
      of 60 months. METHODS: RNA from fresh frozen (FF) and FFPE tumor samples of 82
      patients were used for quality control, and independent FFPE tissues of 342
      postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by
      measuring prospectively selected genes and computing scores representing the
      functions of the estrogen receptor (eight genes, ER_8), the progesterone receptor
      (five genes, PGR_5), Her2 (two genes, HER2_2), and proliferation (ten genes,
      PRO_10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density
      Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2,
      and PRO_10 scores were combined into a RISK_25 score. RESULTS: Pearson
      correlation coefficients between FF- and FFPE-derived scores were at least 0.94
      and high concordance was observed between molecular scores and
      immunohistochemical data. The HER2_2, PGR_5, PRO_10 and RISK_25 scores were
      significant predictors of disease free-survival (DFS) in univariate Cox
      proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in
      patients with histological grade II breast cancer and in lymph node positive
      disease. The PRO_10 and PGR_5 scores were independent predictors of DFS in
      multivariate Cox regression models incorporating clinical risk indicators; PRO_10
      outperformed Ki-67 labeling index in multivariate Cox proportional hazard
      analyses. CONCLUSIONS: Scores representing the endocrine responsiveness and
      proliferation status of breast cancers were developed from gene expression
      analyses based on RNA derived from FFPE tissues. The validation of the molecular
      scores with tumor samples of participants of the BIG 1-98 trial demonstrates that
      such scores can serve as independent prognostic factors to estimate disease free
      survival (DFS) in postmenopausal patients with estrogen receptor positive breast
      cancer.

PMID- 20144232
TI  - Distinct expression patterns of the E3 ligase SIAH-1 and its partner Kid/KIF22 in
      normal tissues and in the breast tumoral processes.
AB  - SIAH proteins are the human members of an highly conserved family of E3 ubiquitin
      ligases. Several data suggest that SIAH proteins may have a role in tumor
      suppression and apoptosis. Previously, we reported that SIAH-1 induces the
      degradation of Kid (KIF22), a chromokinesin protein implicated in the normal
      progression of mitosis and meiosis, by the ubiquitin proteasome pathway. In human
      breast cancer cells stably transfected with SIAH-1, Kid/KIF22 protein level was
      markedly reduced whereas, the Kid/KIF22 mRNA level was increased. This
      interaction has been further elucidated through analyzing SIAH and Kid/KIF22
      expression in both paired normal and tumor tissues and cell lines. It was
      observed that SIAH-1 protein is widely expressed in different normal tissues, and
      in cells lines but showing some differences in western blotting profiles.
      Immunofluorescence microscopy shows that the intracellular distribution of SIAH-1
      and Kid/KIF22 appears to be modified in human tumor tissues compared to normal
      controls. When mRNA expression of SIAH-1 and Kid/KIF22 was analyzed by real-time
      PCR in normal and cancer breast tissues from the same patient, a large variation
      in the number of mRNA copies was detected between the different samples. In most
      cases, SIAH-1 mRNA is decreased in tumor tissues compared to their normal
      counterparts. Interestingly, in all breast tumor tissues analyzed, variations in
      the Kid/KIF22 mRNA levels mirrored those seen with SIAH-1 mRNAs. This concerted
      variation of SIAH-1 and Kid/KIF22 messengers suggests the existence of an
      additional level of control than the previously described protein-protein
      interaction and protein stability regulation. Our observations also underline the
      need to re-evaluate the results of gene expression obtained by qRT-PCR and relate
      it to the protein expression and cellular localization when matched normal and
      tumoral tissues are analyzed.

PMID- 20144233
TI  - SARS coronavirus protein 7a interacts with human Ap4A-hydrolase.
AB  - The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122
      amino acid accessory protein. It has no significant sequence homology with any
      other known proteins. The 7a protein is present in the virus particle and has
      been shown to interact with several host proteins; thereby implicating it as
      being involved in several pathogenic processes including apoptosis, inhibition of
      cellular protein synthesis, and activation of p38 mitogen activated protein
      kinase. In this study we present data demonstrating that the SARS-CoV 7a protein
      interacts with human Ap4A-hydrolase (asymmetrical diadenosine tetraphosphate
      hydrolase, EC 3.6.1.17). Ap4A-hydrolase is responsible for metabolizing the
      "allarmone" nucleotide Ap4A and therefore likely involved in regulation of cell
      proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The
      interaction between 7a and Ap4A-hydrolase was identified using yeast two-hybrid
      screening. The interaction was confirmed by co-immunoprecipitation from cultured
      human cells transiently expressing V5-His tagged 7a and HA tagged Ap4A-hydrolase.
      Human tissue culture cells transiently expressing 7a and Ap4A-hydrolase tagged
      with EGFP and Ds-Red2 respectively show these proteins co-localize in the
      cytoplasm.

PMID- 20144234
TI  - Genome-wide methylation and expression profiling identifies promoter
      characteristics affecting demethylation-induced gene up-regulation in melanoma.
AB  - BACKGROUND: Abberant DNA methylation at CpG dinucleotides represents a common
      mechanism of transcriptional silencing in cancer. Since CpG methylation is a
      reversible event, tumor supressor genes that have undergone silencing through
      this mechanism represent promising targets for epigenetically active anti-cancer
      therapy. The cytosine analog 5-aza-2'-deoxycytidine (decitabine) induces genomic
      hypomethylation by inhibiting DNA methyltransferase, and is an example of an
      epigenetic agent that is thought to act by up-regulating silenced genes. METHODS:
      It is unclear why decitabine causes some silenced loci to re-express, while
      others remain inactive. By applying data-mining techniques to large-scale
      datasets, we attempted to elucidate the qualities of promoter regions that define
      susceptibility to the drug's action. Our experimental data, derived from melanoma
      cell strains, consist of genome-wide gene expression data before and after
      treatment with decitabine, as well as genome-wide data on un-treated promoter
      methylation status, and validation of specific genes by bisulfite sequencing.
      RESULTS: We show that the combination of promoter CpG content and methylation
      level informs the ability of decitabine treatment to up-regulate gene expression.
      Promoters with high methylation levels and intermediate CpG content appear most
      susceptible to up-regulation by decitabine, whereas few of those highly
      methylated promoters with high CpG content are up-regulated. For promoters with
      low methylation levels, those with high CpG content are more likely to be up
      regulated, whereas those with low CpG content are underrepresented among up
      regulated genes. CONCLUSIONS: Clinically, elucidating the patterns of action of
      decitabine could aid in predicting the likelihood of up-regulating epigenetically
      silenced tumor suppressor genes and others from pathways involved with tumor
      biology. As a first step toward an eventual translational application, we build a
      classifier to predict gene up-regulation based on promoter methylation and CpG
      content, which achieves a performance of 0.77 AUC.

PMID- 20144235
TI  - Sleep triggered by an immune response in Drosophila is regulated by the circadian
      clock and requires the NFkappaB Relish.
AB  - BACKGROUND: Immune challenge impacts behavior in many species. In mammals, this
      adaptive behavior is often manifested as an increase in sleep. Sleep has
      therefore been proposed to benefit the host by enhancing immune function and
      thereby overcome the challenge. To facilitate genetic studies on the relationship
      between sleep and immune function, we characterized the effect of the immune
      response on sleep in Drosophila melanogaster. Behavioral features of sleep as
      well as the innate immune response signaling pathways are well characterized in
      flies and are highly conserved in mammals. RESULTS: An immune response induced by
      infection with Gram-negative bacteria or by aseptic injury increased sleep in
      flies. The increase in sleep occurred during the morning hours after treatment
      and the magnitude of the effect was dependent on the time-of-day of inoculation
      or injury such that night-time treatment had a stronger effect than that during
      the daytime. This pattern persisted in constant darkness, indicating a role of
      the circadian clock. Mutants of the circadian clock gene, period, eliminated the
      increase in sleep observed in the morning, but instead showed enhanced sleep
      immediately after injury or infection.Null mutants of the Nuclear Factor kappaB
      (NFkappaB) Relish, which is central to the innate immune response, do not
      increase sleep in response to injury or infection at any time of day. Instead,
      they maintain a normal sleep pattern until they die. Expression of a full-length
      Relish transgene in the fat bodies of Relish mutants restored the morning
      increase in sleep during an immune response. Fat bodies are a major site of
      immune signalling in flies and have a key role in host defense. CONCLUSIONS:
      These data demonstrate that an immune response increases sleep in flies in a
      manner that is gated by the circadian clock and that requires the NFkappaB
      Relish. These findings support a role of sleep in a recovery process and
      demonstrate a conserved feature of the Drosophila model of sleep.

PMID- 20144236
TI  - Simulation of a Petri net-based model of the terpenoid biosynthesis pathway.
AB  - BACKGROUND: The development and simulation of dynamic models of terpenoid
      biosynthesis has yielded a systems perspective that provides new insights into
      how the structure of this biochemical pathway affects compound synthesis. These
      insights may eventually help identify reactions that could be experimentally
      manipulated to amplify terpenoid production. In this study, a dynamic model of
      the terpenoid biosynthesis pathway was constructed based on the Hybrid Functional
      Petri Net (HFPN) technique. This technique is a fusion of three other extended
      Petri net techniques, namely Hybrid Petri Net (HPN), Dynamic Petri Net (HDN) and
      Functional Petri Net (FPN). RESULTS: The biological data needed to construct the
      terpenoid metabolic model were gathered from the literature and from biological
      databases. These data were used as building blocks to create an HFPNe model and
      to generate parameters that govern the global behaviour of the model. The dynamic
      model was simulated and validated against known experimental data obtained from
      extensive literature searches. The model successfully simulated metabolite
      concentration changes over time (pt) and the observations correlated with known
      data. Interactions between the intermediates that affect the production of
      terpenes could be observed through the introduction of inhibitors that
      established feedback loops within and crosstalk between the pathways.
      CONCLUSIONS: Although this metabolic model is only preliminary, it will provide a
      platform for analysing various high-throughput data, and it should lead to a more
      holistic understanding of terpenoid biosynthesis.

PMID- 20144237
TI  - Bisbenzamidine derivative, pentamidine represses DNA damage response through
      inhibition of histone H2A acetylation.
AB  - BACKGROUND: MRE11 is an important nuclease which functions in the end-resection
      step of homologous recombination (HR) repair of DNA double-strand breaks (DSBs).
      As MRE11-deficient ATLD cells exhibit hyper radio-sensitivity and impaired DSB
      repair, MRE11 inhibitors could possibly function as potent radio-sensitizers.
      Therefore, we investigated whether a bisbenzamidine derivative, pentamidine,
      which can inhibit endoexonuclease activity, might influence DSB-induced damage
      responses via inhibition of MRE11. RESULTS: We first clarified that pentamidine
      inhibited MRE11 nuclease activity and also reduced ATM kinase activity in vitro.
      Pentamidine increased the radio-sensitivity of HeLa cells, suggesting that this
      compound could possibly influence DNA damage response factors in vivo. Indeed, we
      found that pentamidine reduced the accumulation of gamma-H2AX, NBS1 and phospho
      ATM at the sites of DSBs. Furthermore, pentamidine decreased HR activity in vivo.
      Pentamidine was found to inhibit the acetylation of histone H2A which could
      contribute both to inhibition of IR-induced focus formation and HR repair. These
      results suggest that pentamidine might exert its effects by inhibiting histone
      acetyltransferases. We found that pentamidine repressed the activity of Tip60
      acetyltransferase which is known to acetylate histone H2A and that knockdown of
      Tip60 by siRNA reduced HR activity. CONCLUSION: These results indicate that
      inhibition of Tip60 as well as hMRE11 nuclease by pentamidine underlies the
      radiosensitizing effects of this compound making it an excellent sensitizer for
      radiotherapy or chemotherapy.

PMID- 20144238
TI  - Quality of care and health-related quality of life of climacteric stage women
      cared for in family medicine clinics in Mexico.
AB  - OBJECTIVES: 1) To design and validate indicators to measure the quality of the
      process of care that climacteric stage women receive in family medicine clinics
      (FMC). 2) To assess the quality of care that climacteric stage women receive in
      FMC. 3) To determine the association between quality of care and health-related
      quality of life (HR-QoL) among climacteric stage women. METHODS: The study had
      two phases: I. Design and validation of indicators to measure the quality of care
      process by using the RAND/UCLA Appropriateness Method. II. Evaluation of the
      quality of care and its association with HR-QoL through a cross-sectional study
      conducted in two FMC located in Mexico City that included 410 climacteric stage
      women. The quality of care was measured by estimating the percentage of
      recommended care received (PRCR) by climacteric stage women in three process
      components: health promotion, screening, and treatment. The HR-QoL was measured
      using the Cervantes scale (0-155). The association between quality of care and HR
      QoL was estimated through multiple linear regression analysis. RESULTS: The
      lowest mean of PRCR was for the health promotion component (24.1%) and the
      highest for the treatment component (86.6%). The mean of HR-QoL was 50.1 points.
      The regression analysis showed that in the treatment component, for every 10
      additional points of the PRCR, the global HR-QoL improved 2.8 points on the
      Cervantes scale (coefficient -0.28, P < 0.0001). CONCLUSION: The indicators to
      measure quality of care for climacteric stage women are applicable and feasible
      in family medicine settings. There is a positive association between the quality
      of the treatment component and HR-QoL; this would encourage interventions to
      improve quality of care for climacteric stage women.

PMID- 20144239
TI  - Baculovirus immediately early 1, a mediator for homologous regions enhancer
      function in trans.
AB  - BACKGROUND: Enhancers are DNA sequences that serve as binding sites for
      regulatory proteins, and stimulate transcriptional activity independent of their
      positions and orientations with respect to the transcriptional initiation site.
      Previous studies considered that baculovirus homologous regions (hrs) function as
      enhancers in cis. In our study, a plasmid containing homologous region 3 (hr3)
      enhancer from Bombyx mori nucleopolyhedrovirus (BmNPV) failed to enhance
      transcription of promoter in other plasmid in co-transfection assays, but strong
      stimulation occurred when cells were infected by BmNPV. RESULTS: The
      cotransfection results of each BmNPV genomic library plasmid, hr3 plasmid and
      reporter plasmid showed that there were eight library plasmids stimulated the
      luciferase gene expression remarkably. Sequencing these plasmids revealed that
      each of them contained the ie-1 gene. Transfected plasmids, containing ie-1, hr3
      and various origin promoter drove reporter gene showed the function was even
      retained. Cotransfection of hr3 functional dissected fragment and ie-1 revealed
      that the 30-bp imperfect palindrome destroyed fragment can't enhance reporter
      gene expression even though transfected with ie-1. CONCLUSION: IE-1 was the only
      early factor of BmNPV that could act as a mediator for hr enhancer function in
      trans and the trans-function was achieved with a broad-spectrum of promoters. The
      30-bp imperfect palindrome was the elementary molecular structure by which IE-1
      participated in the enhancer function in trans.

PMID- 20144240
TI  - A dual function TAR Decoy serves as an anti-HIV siRNA delivery vehicle.
AB  - The TAR RNA of HIV was engineered as an siRNA delivery vehicle to develop a
      combinatorial therapeutic approach. The TAR backbone was found to be a versatile
      backbone for expressing siRNAs. Upon expression in human cells, pronounced and
      specific inhibition of reporter gene expression was observed with TARmiR. The
      resulting TARmiR construct retained its ability to bind Tat and mediate RNAi.
      TARmiR was able to inhibit HIV gene expression as a TAR decoy and by RNA
      interference when challenged with infectious proviral DNA. The implications of
      this dual function therapeutic would be discussed.

PMID- 20144241
TI  - Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N
      myc expression.
AB  - Neuroblastoma is a pediatric malignancy characterized by tremendous clinical
      heterogeneity, in which some tumors are extremely aggressive while others
      spontaneously differentiate into benign forms. Because the degree of
      differentiation correlates with prognosis, and because differentiating agents
      such as retinoic acid (RA) have proven to decrease mortality, much effort has
      been devoted to identifying critical regulators of neuroblastoma differentiation
      in the cellular microenvironment, including cues encoded in the extracellular
      matrix (ECM). While signaling between tumor cells and the ECM is classically
      regarded to be based purely on biochemical recognition of ECM ligands by specific
      cellular receptors, a number of recent studies have made it increasingly clear
      that the biophysical properties of the ECM may also play an important role in
      this cross-talk. Given that RA-mediated neuroblastoma differentiation is
      accompanied by profound changes in cell morphology and neurite extension, both of
      which presumably rely upon mechanotransductive signaling systems, it occurred to
      us that mechanical cues from the ECM might also influence RA-mediated
      differentiation, which in turn might regulate clinically-relevant aspects of
      neuroblastoma biology. In this study, we tested this hypothesis by subjecting a
      series of neuroblastoma culture models to ECM microenvironments of varying
      mechanical stiffness and examined the regulatory role of ECM stiffness in
      proliferation, differentiation, and expression of tumor markers. We find that
      increasing ECM stiffness enhances neuritogenesis and suppresses cell
      proliferation. Remarkably, increasing ECM stiffness also reduces expression of N
      Myc, a transcription factor involved in multiple aspects of oncogenic
      proliferation that is used for evaluating prognosis and clinical grading of
      neuroblastoma. Furthermore, the addition of RA enhances all of these effects for
      all ECM stiffnesses tested. Together, our data strongly support the notion that
      the mechanical signals from the cellular microenvironment influence neuroblastoma
      differentiation and do so synergistically with RA. These observations support
      further investigation of the role of microenvironmental mechanical signals in
      neuroblastoma proliferation and differentiation and suggest that pharmacological
      agents that modulate the underlying mechanotransductive signaling pathways may
      have a role in neuroblastoma therapy.

PMID- 20144242
TI  - Genetic analysis of patients with Fuchs endothelial corneal dystrophy in India.
AB  - BACKGROUND: Mutations in COL8A2 gene which encodes the collagen alpha-2 (VIII)
      chain have been identified in both familial and sporadic cases of Fuchs
      endothelial corneal dystrophy (FECD). Heterozygous mutations in the SLC4A11 gene
      are also known to cause late-onset FECD. Therefore we screened for COL8A2,
      SLC4A11 gene variants in Indian FECD patients. METHODS: Eighty patients with
      clinically diagnosed FECD and 100 age matched normal individuals were recruited.
      Genomic DNA was isolated from peripheral blood leukocytes. Mutations in COL8A2,
      SLC4A11 coding regions were screened using bi-directional sequencing. Fischer's
      exact test or Pearson's chi squared test were used to predict the statistical
      association of genotypes with the phenotype. RESULTS: Screening of COL8A2 gene
      revealed 2 novel c.1610G>A, c.1643A>G and 3 reported variations c.112G>A,
      c.464G>A and c.1485G>A. In SLC4A11 gene, novel c.1659C>T, c.1974C>T and reported
      c.405G>A, c.481A>C and c.639G>A variants were identified. However all the
      variations in both the genes were also present in unaffected controls.
      CONCLUSIONS: This is the first study analysing COL8A2 gene in Indian patients
      with FECD. No pathogenic mutations were identified in COL8A2. Merely silent
      changes, which showed statistically insignificant association with FECD, were
      identified in the screening of SLC4A11 gene. These results suggest that COL8A2,
      SLC4A11 genes may not be responsible for FECD in patients examined in this study.

PMID- 20144243
TI  - An ethnozoological study in the adjoining areas of Mount Abu wildlife sanctuary,
      India.
AB  - BACKGROUND: There is evidence that human beings are familiar with use of animals
      for food, cloth, medicine, etc. since ancient times. Enormous work has been done
      on ethnobotany and traditional medicine. Like plants, animal and their products
      are also possessing medicinal properties that can be exploited for the benefit of
      human beings. In India, many ethnic communities are dispersed all over the
      country and these people are still totally depended on local traditional
      medicinal system for their health care. India is gifted with faunal and floral
      biodiversity, Mount Abu wildlife sanctuary is also one of them, and thus the aim
      of this work was to take an ethnozoological field survey among Garasiya people
      (main tribal group of this area) in the adjoining areas of this sanctuary.
      METHOD: In order to document the ethnozoological information about animal and
      their products prevalent among these people in the adjoining area of Mount Abu
      wildlife sanctuary, a study was carried out from January, 2008 to April, 2008.
      Data were collected through semi-structured questionnaire and open interview with
      25 (16 male and 9 female) selected Garasiya people. The name of animal and other
      ethnozoological information were documented. Photographs and discussion were also
      recorded with the help of camera and voice recorder. RESULT: A total of 24 animal
      species were used in 35 different medicinal purposes including asthma, weakness,
      tuberculosis, cough, paralysis and blister and for other religious purposes. It
      has been find out that animal used by Garasiya, consist of fourteen mammals, five
      birds, three reptiles, one arthropods and one amphibian. The meat of Cynopterus
      sphinx used to relieved fever and cough has the highest FL (96%) although flesh
      of Sus scrofa and tooth of Elephas maximus have the lowest FL (12%). Some
      protected species such as Elephas maximus (elephant), Semnopithecus priam
      (monkey), Cervus unicolor (sambhar) were also mentioned as important medicinal
      resources. We also found that cough, asthma and other respiratory diseases are
      the most frequently cited disease, as such, a number of traditional medicine are
      available for the treatment. CONCLUSION: The present work indicates that 24
      animal species were being used to treat 34 various ailments in the surroundings
      areas of Mount Abu wildlife sanctuary. The results show that ethnozoological
      practices are an important alternative medicinal practice for the Garasiya
      people. This study also indicates the very rich ethnozoological knowledge of
      these people in relation to traditional medicine. So there is an urgent need to
      properly document to keep a record of the ethnozoological information. We hope
      that this information will be useful for further research in the field of
      ethnozoology, ethnopharmacology and conservation point of view.

PMID- 20144244
TI  - Evaluation of an open access echocardiography service in the Netherlands: a mixed
      methods study of indications, outcomes, patient management and trends.
AB  - BACKGROUND: In our region (Eastern South Limburg, The Netherlands) an open access
      echocardiography service started in 2002. It was the first service of this kind
      in The Netherlands. Our study aims were: (1) to evaluate demand for the service,
      participation, indications, echocardiography outcomes, and management by the
      general practitioner (GP); (2) to analyse changes in indications and outcomes
      over the years. METHODS: (1) Data from GP request forms, echocardiography reports
      and a retrospective GP questionnaire on management (response rate 83%) of 625
      consecutive patients (Dec. 2002-March 2007) were analysed cross-sectionally. (2)
      For the analysis of changes over the years, data from GP request forms and
      echocardiography reports of the first and last 250 patients that visited the
      service between Dec. 2002 and Feb. 2008 (n = 1001) were compared. RESULTS: The
      echocardiography service was used by 81% of the regional GPs. On average, a GP
      referred one patient per year to the service. Intended indications for the
      service were dyspnoea (32%), cardiac murmur (59%), and peripheral oedema (17%).
      Of the other indications (22%), one-third was for evaluation of suspected left
      ventricular hypertrophy (LVH). Expected outcomes were left ventricular
      dysfunction (LVD) (43%, predominantly diastolic) and valve disease (25%). We also
      found a high proportion of LVH (50%). Only 24% of all echocardiograms showed no
      relevant disease. The GP followed the cardiologist's advice to refer the patient
      for further evaluation in 71%. In recent patients, more echocardiography requests
      were done for 'cardiac murmur' and 'other' indications, but less for 'dyspnoea'.
      The proportions of patients with LVD, LVH and valve disease decreased and the
      proportion of patients with no relevant disease increased. The number of advices
      by the cardiologists increased. CONCLUSION: Overall, GPs used the open access
      echocardiography service efficiently (i.e. with a high chance of finding relevant
      pathology), but efficiency decreased slightly over the years. To meet the needs
      of the GPs, indications might be widened with 'suspicion LVH'. Further
      specification of the indications for open access echocardiography--by defining a
      stepwise diagnostic approach including ECG and (NT-pro)BNP--might improve the
      service.

PMID- 20144245
TI  - Expression, purification and characterization of the Lily symptomless virus coat
      protein from Lanzhou Isolate.
AB  - BACKGROUND: Lily symptomless virus (LSV) is widespread in many countries where
      lily are grown or planted, and causes severe economic losses in terms of quantity
      and quality of flower and bulb production. To study the structure-function
      relationship of coat protein (CP) of LSV, to investigate antigenic relationships
      between coat protein subunits or intact virons, and to prepare specific
      antibodies against LSV, substantial amounts of CP protein are needed. RESULTS:
      Thus, full-length cDNA of LSV coat protein was synthesized and amplified by RT
      PCR from RNA isolated from LSV Lanzhou isolate. The extended 33.6 kDa CP was
      cloned and expressed prokaryoticly and then purified by Ni-ion affinity
      chromatography. Its identity and antigenicity of recombinant CP were identified
      on Western-blotting by using the prepared anti-LSV antibodies. CONCLUSIONS: The
      results indicate that fusion CP maintains its native antigenicity and
      specificity, providing a good source of antigen in preparation of LSV related
      antibodies. Detailed structural analysis of a pure recombinant CP should allow a
      better understanding of its role in cell attachment and LSV tropism. This
      investigation to LSV should provide some specific antibodies and aid to
      development a detection system for LSV diagnostics and epidemiologic surveys.

PMID- 20144246
TI  - A candidate probiotic with unfavourable effects in subjects with irritable bowel
      syndrome: a randomised controlled trial.
AB  - BACKGROUND: Some probiotics have shown efficacy for patients with irritable bowel
      syndrome (IBS). Lactobacillus (L.) plantarum MF1298 was found to have the best in
      vitro probiotic properties of 22 strains of lactobacilli. The aim of this study
      was to investigate the symptomatic effect of L. plantarum MF1298 in subjects with
      IBS. Primary outcome was treatment preference and secondary outcomes were number
      of weeks with satisfactory relief of symptoms and IBS sum score. METHODS: The
      design was a randomised double blind placebo-controlled crossover trial. 16
      subjects with IBS underwent two three-week periods of daily intake of one capsule
      of 10(10) CFU L. plantarum MF 1298 or placebo separated by a four-week washout
      period. RESULTS: Thirteen participants (81%; 95% CI 57% to 93%; P = 0.012)
      preferred placebo to L. plantarum MF1298 treatment. The mean (SD) number of weeks
      with satisfactory relief of symptoms in the periods with L. plantarum MF1298 and
      placebo were 0.50 (0.89) and 1.44 (1.26), respectively (P = 0.006). IBS sum score
      was 6.44 (1.81) in the period with L. plantarum MF1298 treatment compared with
      5.35 (1.77) in the period with placebo (P = 0.010). With a clinically significant
      difference in the IBS sum score of 2 in disfavour of active treatment, the number
      needed to harm was 3.7, 95% CI 2.3 to 10.9. CONCLUSIONS: This trial shows for the
      first time an unfavourable effect on symptoms in subjects with IBS after intake
      of a potential probiotic.

PMID- 20144247
TI  - Cross-cultural adaptation of research instruments: language, setting, time and
      statistical considerations.
AB  - BACKGROUND: Research questionnaires are not always translated appropriately
      before they are used in new temporal, cultural or linguistic settings. The
      results based on such instruments may therefore not accurately reflect what they
      are supposed to measure. This paper aims to illustrate the process and required
      steps involved in the cross-cultural adaptation of a research instrument using
      the adaptation process of an attitudinal instrument as an example. METHODS: A
      questionnaire was needed for the implementation of a study in Norway 2007. There
      was no appropriate instruments available in Norwegian, thus an Australian-English
      instrument was cross-culturally adapted. RESULTS: The adaptation process included
      investigation of conceptual and item equivalence. Two forward and two back
      translations were synthesized and compared by an expert committee. Thereafter the
      instrument was pretested and adjusted accordingly. The final questionnaire was
      administered to opioid maintenance treatment staff (n=140) and harm reduction
      staff (n=180). The overall response rate was 84%. The original instrument failed
      confirmatory analysis. Instead a new two-factor scale was identified and found
      valid in the new setting. CONCLUSIONS: The failure of the original scale
      highlights the importance of adapting instruments to current research settings.
      It also emphasizes the importance of ensuring that concepts within an instrument
      are equal between the original and target language, time and context. If the
      described stages in the cross-cultural adaptation process had been omitted, the
      findings would have been misleading, even if presented with apparent precision.
      Thus, it is important to consider possible barriers when making a direct
      comparison between different nations, cultures and times.

PMID- 20144248
TI  - Overcoming trends in irregularly spaced locations by regional polish -
      exemplified by estimation of the range of influence between Salmonella Dublin
      seropositive cattle herds.
AB  - The aim of the study was to develop a procedure to remove spatial trends in
      irregularly spaced data, with trends partly due to regional differences. Median
      polish is often used on regularly spaced (lattice) data where column and row
      medians are removed. For irregularly spaced data a low-resolution map of the
      spatial locations is often used where data locations are assigned to the nearest
      lattice node followed by median polish. In this study regional polish was
      developed. The inverse distance weighted median was calculated based on
      observations from locations in the neighbourhood of the actual observation. The
      regional polish residual is obtained as the difference between the observed value
      and the weighted median. The regional polish procedure was applied to Salmonella
      Dublin data showing strong regional trends. Estimation of the range of influence
      between cattle herds with positive S. Dublin herd status was considerably
      improved with a stable parameter estimate and reduced standard error.

PMID- 20144249
TI  - The 2007 dengue outbreak in Singapore.

PMID- 20144250
TI  - Emergence of MRSA clone ST22 in healthy young adults in the community in the
      absence of risk factors.
AB  - One thousand adults aged between 18 and 35 years were investigated for nasal
      colonization with community-acquired methicillin-resistant Staphylococcus aureus
      (CA-MRSA). Each volunteer completed a questionnaire to assess the presence or
      absence of risk factors for hospital-acquired MRSA (HA-MRSA) carriage. All MRSA
      isolated were characterized by microbiological and molecular methods. A S. aureus
      carriage rate of 22% and a MRSA carriage rate of 0.7% were observed. Analysis of
      the questionnaires revealed 121 individuals with HA-MRSA risk factors.
      Subsequently two MRSA infections with associated risk factors were excluded from
      calculation of the true carriage rate and an adjusted rate of 0.57% (5/879) was
      established. All seven MRSA isolates expressed the genotypic profile ST22-MRSA
      IV, were PVL negative, agr type 1, and differed only by their antimicrobial
      susceptibility patterns. ST22-MRSA-IV (EMRSA-15) has shown worldwide spread in
      the hospital setting but has not been previously documented in isolation in the
      community.

PMID- 20144251
TI  - Prevalence and clinical correlations of genetic subtypes of Giardia lamblia in an
      urban setting.
AB  - The clinical significance of different genetic subtypes or assemblages of Giardia
      lamblia is uncertain. Cases of giardiasis in south-west London between 1999 and
      2005 were studied, comparing molecular-typing results with clinical and
      epidemiological findings from routine surveillance. We identified 819 cases, of
      whom 389 returned surveillance questionnaires. A subset of 267 faecal samples was
      submitted for typing by sequencing of the triose phosphate isomerase (tpi) and
      ribosomal RNA genes, and/or a separate duplex PCR of the tpi gene. Typing was
      successful in 199 (75%) samples by at least one of the molecular methods.
      Assemblage A accounted for 48 (24%) samples and Assemblage B for 145 (73%); six
      (3%) were mixed. Both assemblages had similar seasonality, age distribution and
      association with travel. Clinical features were available for 59 successfully
      typed cases: both assemblages caused similar illness, but Assemblage A was
      significantly more frequently associated with fever than Assemblage B.

PMID- 20144252
TI  - The use of a new virtual cohort study design to investigate an outbreak of E.
      coli O157 linked to a supermarket delicatessen.
AB  - In outbreaks of foodborne disease associated with retail outlets, the outlet
      often closes as a precaution before the specific food vehicle has been
      identified. Suspect food vehicles may be named as part of general control
      measures. A conventional case-control study cannot be performed because both
      cases and potential controls are likely to be aware of the hypothesis and
      therefore potentially biased. Modern sales recording systems in many food retail
      outlets may provide a basis for constructing a virtual cohort and allow a
      statistical inference to be made about various possible vehicles of infection. In
      2007, an outbreak of E. coli O157 infection in Paisley, Scotland, was linked to
      cooked meat from a supermarket delicatessen using descriptive epidemiology.
      Construction of a virtual cohort allowed a relative risk and confidence interval
      to be estimated which supported the hypothesis of cooked beef topside being the
      vehicle of infection. This novel method could be valuable in the investigation of
      future outbreaks.

PMID- 20144253
TI  - Trichinella infection in a hunting community in East Greenland.
AB  - Trichinella nativa infection (trichinellosis) is highly prevalent in Arctic
      wildlife, but the human burden of trichinellosis in present-day Greenland is
      unknown. The study aimed to determine Trichinella seroprevalence in an eastern
      Greenlandic hunting community and to evaluate risk factors for seropositivity.
      Overall, 998 inhabitants aged 10 years in the Ammassalik municipality were tested
      for Trichinella-specific IgG antibodies. Background information was obtained from
      questionnaires. Seropositivity was 1.4% in persons aged <40 years and increased
      to >12% in those aged 60 years. Older age, occupation as hunter or fisherman, and
      consumption of polar bear meat significantly increased the risk of Trichinella
      seropositivity. The seropositivity age pattern probably reflects changes in
      dietary preferences, but could also reflect mandatory meat inspection since 1966.
      However, preventive measures against Trichinella infection should be strengthened
      in Greenland.

PMID- 20144254
TI  - A modelling study of atrial septostomy for pulmonary arterial hypertension, and
      its effect on the state of tissue oxygenation and systemic blood flow.
AB  - Atrial septostomy is performed in patients with severe pulmonary arterial
      hypertension, and has been shown to improve symptoms, quality of life and
      survival. Despite recognized clinical benefits, the underlying pathophysiologic
      mechanisms are poorly understood. We aimed to assess the effects of right-to-left
      shunting on arterial delivery of oxygen, mixed venous content of oxygen, and
      systemic cardiac output in patients with pulmonary arterial hypertension and a
      fixed flow of blood to the lungs. We formulated equations defining the mandatory
      relationship between physiologic variables and delivery of oxygen in patients
      with right-to-left shunting. Using calculus and computer modelling, we considered
      the simultaneous effects of right-to-left shunting on physiologies with different
      pulmonary flows, total metabolic rates, and capacities for carrying oxygen. Our
      study indicates that, when the flow of blood to the lungs is fixed, increasing
      right-to-left shunting improves systemic cardiac output, arterial blood pressure,
      and arterial delivery of oxygen. In contrast, the mixed venous content of oxygen,
      which mirrors the average state of tissue oxygenation, remains unchanged. Our
      model suggests that increasing the volume of right-to-left shunting cannot
      compensate for right ventricular failure. Atrial septostomy in the setting of
      pulmonary arterial hypertension, therefore, increases the arterial delivery of
      oxygen, but the mixed systemic saturation of oxygen, arguably the most important
      index of tissue oxygenation, stays constant. Our data suggest that the clinically
      observed beneficial effects of atrial septostomy are the result of improved flow
      of blood rather than augmented tissue oxygenation, provided that right
      ventricular function is adequate.

PMID- 20144255
TI  - Associations between being overweight, variability in heart rate, and well-being
      in the young men.
AB  - Abnormalities of the autonomic nervous system have been repeatedly shown in
      hypertension. We studied the associations between being overweight, blood
      pressure, cardiac vagal tone as measured by variability in heart rate, and well
      being in a large cohort of young men. We hypothesised an inverse correlation
      between body mass index and the variability in heart rate. Further, we assessed
      systolic and diastolic blood pressure as traditional indicators of cardiovascular
      risk. Exclusion criteria were the use of drugs or pharmaceuticals. The following
      data from 786 men with a mean age of 19.4 years (standard deviation = 1.4, with a
      range from 16 to 24 years) were analysed in a cross-sectional study: body mass
      index, sleep duration, sporting activities, psychological well-being, blood
      pressure, heart rate, and variability in heart rate. Despite the young age of the
      men in this study, increased values for the body mass index were already
      associated with a shift in sympathovagal balance trending towards sympathetic
      dominance. There was also a significant positive correlation between body mass
      index and systolic and diastolic blood pressure. A multiple stepwise regression
      analysis showed that significant factors, which were associated with variability
      in heart rate, were body mass index and sporting activities. In addition,
      sporting activity and sleep duration had a significant positive impact on
      psychological well-being. Even in young men, being overweight is associated with
      increased cardiovascular risk, especially an increased sympathetic and/or lowered
      cardiovascular tone and increased blood pressure. Our study gives additional
      motivation for the early prevention and treatment of obesity in childhood and
      adolescence.

PMID- 20144256
TI  - Sweetened beverage consumption and increased risk of metabolic syndrome in
      Mexican adults.
AB  - OBJECTIVE: To examine the relationship between sweetened beverage consumption and
      components of the metabolic syndrome in a Mexican population. DESIGN: We
      performed a cross-sectional analysis of data from selected adults participating
      in the baseline assessment of the Health Workers Cohort Study. Information on
      participants' sociodemographic characteristics, dietary patterns and physical
      activity were collected via self-administered questionnaires. Sweetened beverage
      consumption was evaluated through a validated semi-quantitative FFQ.
      Anthropometric and clinical measures were assessed with standardized procedures.
      The definition of metabolic syndrome was determined using criteria from the
      National Cholesterol Education Program Adult Treatment Panel III. The
      associations of interest were evaluated by means of linear and logistic
      regression models. SETTING: The Mexican states of Morelos and Mexico. SUBJECTS: A
      total of 5240 individuals aged 20 to 70 years (mean 39.4 (sd 11.5) years) were
      evaluated. RESULTS: Overweight/obesity prevalence was 56.6 %. The prevalence of
      metabolic syndrome in this sample was 26.6 %. We found that for each additional
      daily sweetened beverage serving consumed, participants experienced an average
      increase of 0.49 mmol/l in TAG and a decrease in HDL cholesterol of 0.31 mmol/l.
      Subjects consuming more than two servings of sweetened beverages daily were at
      2.0 times greater risk of metabolic syndrome than those who did not consume
      sweetened beverages. We also observed that higher sweetened beverage consumption
      increased the risk of all components of the metabolic syndrome. CONCLUSIONS: Our
      data support the hypothesis that sweetened beverage consumption increases the
      risk of metabolic syndrome in Mexican adults, possibly by providing excess energy
      and large amounts of rapidly absorbable sugars.

PMID- 20144257
TI  - Family meals and adolescents: what have we learned from Project EAT (Eating Among
      Teens)?
AB  - OBJECTIVE: The purpose of the present paper is to provide an integrated overview
      of the research methodology and key findings from a decade of research on family
      meals as part of Project EAT (Eating Among Teens), a large, population-based
      study of adolescents. DESIGN: Focus groups conducted with 141 middle-school and
      high-school adolescents suggested the importance of family meals in influencing
      adolescents' food choices. These findings led to the inclusion of questions on
      family meals in the Project EAT-I survey, completed by 4746 middle-school and
      high-school students, and in the Project EAT-II longitudinal survey, completed by
      2516 of the original participants five years later. A subset of 902 parents also
      participated in telephone interviews as part of Project EAT-I. RESULTS: Findings
      indicate that many adolescents and parents view family meals in a positive light,
      but there is great diversity in the context and frequency of family meal patterns
      in the homes of adolescents. Findings further suggest that family meals may have
      benefits in terms of dietary intake, disordered eating behaviours, substance use
      and psychosocial health. CONCLUSIONS: Findings from Project EAT, in conjunction
      with other research studies on family meals, suggest the importance of working
      with families to increase the frequency and improve the quality of family meals.
      Further research is needed in order to elucidate the pathways that underpin the
      relationships between family meals and health outcomes. Suggestions for a future
      research agenda based on what was learned from Project EAT are provided.

PMID- 20144258
TI  - Effects of green tea, black tea and Rooibos tea on angiotensin-converting enzyme
      and nitric oxide in healthy volunteers.
AB  - OBJECTIVE: Tea has been reported to reduce cardiovascular mortality, but the
      underlying mechanisms are largely unknown. The aim of the current project was to
      investigate the effect of green tea (Japanese Sencha), black tea (Indian Assam
      B.O.P.) and Rooibos tea (South Africa) on angiotensin-converting enzyme (ACE) and
      nitric oxide (NO). DESIGN: Seventeen healthy volunteers received a single oral
      dose of 400 ml green tea, black tea or Rooibos tea in a randomized, three-phase,
      crossover study. ACE activity and NO concentration were measured (at 0, 30, 60
      and 180 min) in all phases. ACE activity was analysed by means of a commercial
      radioenzymatic assay. Nitrite was analysed as a marker of NO concentration. In
      addition, ACE genotype was determined using a PCR method. RESULTS: Oral intake of
      a single dose of Rooibos tea significantly inhibited ACE activity after 30 min (P
      < 0.01) and after 60 min (P < 0.05). A significant inhibition of ACE activity was
      seen with green tea for the ACE II genotype 30 min after intake of the tea (P <
      0.05) and for the ACE ID genotype 60 min after intake (P < 0.05). A significant
      inhibition of ACE activity was also seen with Rooibos tea for the ACE II genotype
      60 min after intake (P < 0.05). No significant effect on NO concentration was
      seen. CONCLUSIONS: These results suggest that green tea and Rooibos tea may have
      cardiovascular effects through inhibition of ACE activity.

PMID- 20144259
TI  - The effects of a school-based intervention programme on dietary intakes and
      physical activity among primary-school children in Trinidad and Tobago.
AB  - OBJECTIVE: Childhood obesity is increasingly being recognized as a major public
      health problem in the Caribbean. The objective of the present study was to
      evaluate the effectiveness of a short-term, school-based, multi-component
      education intervention on improving the knowledge, attitudes and behaviour of
      primary-school children towards better dietary and activity habits. DESIGN: The
      study was a randomized, controlled, school-based nutrition education and physical
      activity intervention. Participating schools were randomly assigned to the
      intervention (IVG) and non-intervention (NIVG) groups. SETTING: All primary
      schools in Sangre Grande, north-east Trinidad. SUBJECTS: Five hundred and seventy
      nine pupils in their sixth year of primary-school education were enrolled from
      twelve schools in Sangre Grande, north-east Trinidad. RESULTS: Approximately 23 %
      of participants had BMI >or= 85th percentile of the Centers for Disease Control
      and Prevention age- and gender-specific cut-off values. In multivariate
      regression equations controlling for age, gender, BMI and baseline value,
      intervention was associated with lower intake levels of fried foods, snack foods
      high in fat, sugar and salt (HFSS) and sodas (P < 0.05). In similar analyses,
      intervention was associated with higher knowledge scores (P < 0.01). Intervention
      was not significantly associated with physical activity and Children's Eating
      Attitude Test-26 (ChEAT26) scores after controlling for age, gender, BMI and the
      relevant baseline values. CONCLUSIONS: The intervention was associated with lower
      intake levels of fried foods, HFSS foods, sodas and higher knowledge scores
      independent of age, gender, BMI, ethnicity and the appropriate baseline value.
      Finally, the intervention was not associated with changes in physical activity
      behaviours in multivariate analyses.

PMID- 20144260
TI  - A serological study of Dirofilaria immitis in feral cats in Grenada, West Indies.
AB  - A study to determine the seroprevalence of Dirofilaria immitis was carried out in
      feral cats in Grenada. Of the 137 feral cats tested for circulating antibodies
      (IgG; lateral-flow immunoassay) and circulating antigens (Ag; enzyme-linked
      immunosorbent assay), 8% (95% confidence interval (CI) 3.5-12.5%) were antibody
      positive and 5.1% (95% CI 1.4-8.8%) were antigen positive. No significant
      difference between cats aged>1 to 4 years and cats less than 1 year of age was
      found (P>0.05, chi2). There was also no significant difference (P>0.05, chi2)
      between male and female cats. Dirofilaria immitis prevalence is relatively high
      in the feral cat population of Grenada. Evidence of D. immitis infection in feral
      cats coupled with the endemic nature of heartworm disease in dogs in Grenada
      leads us to suggest the introduction of heartworm prophylaxis in cats. To the
      authors' knowledge, this serological evidence of heartworm infection in feral
      cats in Grenada is the first report from the Caribbean region.

PMID- 20144261
TI  - Transplant of GABAergic precursors restores hippocampal inhibitory function in a
      mouse model of seizure susceptibility.
AB  - Defects in GABAergic function can cause epilepsy. In the last years, cell-based
      therapies have attempted to correct these defects with disparate success on
      animal models of epilepsy. Recently, we demonstrated that medial ganglionic
      eminence (MGE)-derived cells grafted into the neonatal normal brain migrate and
      differentiate into functional mature GABAergic interneurons. These cells are able
      to modulate the local level of GABA-mediated synaptic inhibition, which suggests
      their suitability for cell-based therapies. However, it is unclear whether they
      can integrate in the host circuitry and rescue the loss of inhibition in
      pathological conditions. Thus, as proof of principle, we grafted MGE-derived
      cells into a mouse model of seizure susceptibility caused by specific elimination
      of GABAergic interneuron subpopulations in the mouse hippocampus after injection
      of the neurotoxic saporin conjugated to substance P (SSP-Sap). This ablation was
      associated with significant decrease in inhibitory postsynaptic currents (IPSC)
      on CA1 pyramidal cells and increased seizure susceptibility induced by
      pentylenetetrazol (PTZ). Grafting of GFP(+) MGE-derived cells in SSP-Sap-treated
      mice repopulates the hippocampal ablated zone with cells expressing molecular
      markers of mature interneurons. Interestingly, IPSC kinetics on CA1 pyramidal
      cells of ablated hippocampus significantly increased after transplantation,
      reaching levels similar to the normal mice. More importantly, this was associated
      with reduction in seizure severity and decrease in postseizure mortality induced
      by PTZ. Our data show that MGE-derived cells fulfill most of the requirements for
      an appropriate cell-based therapy, and indicate their suitability for
      neurological conditions where a modulation of synaptic inhibition is needed, such
      as epilepsy.

PMID- 20144262
TI  - The efficient generation of induced pluripotent stem (iPS) cells from adult mouse
      adipose tissue-derived and neural stem cells.
AB  - Ectopic expression of key reprogramming transgenes in somatic cells enables them
      to adopt the characteristics of pluripotency. Such cells have been termed induced
      pluripotent stem (iPS) cells and have revolutionized the field of somatic cell
      reprogramming, as the need for embryonic material is obviated. One of the issues
      facing both the clinical translation of iPS cell technology and the efficient
      derivation of iPS cell lines in the research laboratory is choosing the most
      appropriate somatic cell type for induction. In this study, we demonstrate the
      direct reprogramming of a defined population of neural stem cells (NSCs) derived
      from the subventricular zone (SVZ) and adipose tissue-derived cells (ADCs) from
      adult mice using retroviral transduction of the Yamanaka factors Oct4, Sox2,
      Klf4, and c-Myc, and compared the results obtained with a mouse embryonic
      fibroblast (mEF) control. We isolated mEFs, NSCs, and ADCs from transgenic mice,
      which possess a GFP transgene under control of the Oct4 promoter, and validated
      GFP expression as an indicator of reprogramming. While transduction efficiencies
      were not significantly different among the different cell types (mEFs 68.70 +/-
      2.62%, ADCs 70.61 +/- 15.4%, NSCs, 68.72 +/- 3%, p = 0.97), the number of GFP
      positive colonies and hence the number of reprogramming events was significantly
      higher for both NSCs (13.50 +/- 4.10 colonies, 0.13 +/- 0.06%) and ADCs (118.20
      +/- 38.28 colonies, 1.14 +/- 0.77%) when compared with the mEF control (3.17 +/-
      0.29 colonies, 0.03 +/- 0.005%). ADCs were most amenable to reprogramming with an
      8- and 38-fold greater reprogramming efficiency than NSCs and mEFs, respectively.
      Both NSC iPS and ADC iPS cells were demonstrated to express markers of
      pluripotency and could differentiate to the three germ layers, both in vitro and
      in vivo, to cells representative of the three germ lineages. Our findings confirm
      that ADCs are an ideal candidate as a readily accessible somatic cell type for
      high efficiency establishment of iPS cell lines.

PMID- 20144263
TI  - Establishing a Trainee Section in the CIM.

PMID- 20144264
TI  - Mutations of the TGFBR2 gene in Chinese patients with Marfan-related syndrome.
AB  - PURPOSE: Transforming growth factor beta receptors II gene (TGFBR2) mutations
      associated with Marfan syndrome and Marfan-associated disorders have been
      investigated. However, such studies are limited in China. To obtain more
      information about TGFBR2 mutations, we analyzed 6 unrelated Chinese patients with
      Marfan-associated disorders and without ocular manifestation. METHODS: The
      genomic DNA from blood leukocytes of these 6 patients and their relatives was
      isolated, and the entire coding region of TGFBR2 was amplified using PCR. We
      determined the sequence of TGFBR2 with the ABI 3100 Genetic Analyzer. RESULTS:
      Three mutations were identified in TGFBR2. Two mutations were associated with
      Loeys-Dietz syndrome (LDS), which were distributed as following: one missense
      mutation R528C (caused by a 1582C > T substitution) and one polymorphism T315M (a
      rare SNP). The third mutation was a novel silent mutation associated with MFS2,
      which was K291K caused by an 873 C > T substitution. CONCLUSIONS: The TGFBR2 gene
      missense mutations are possibly causative mutations of Loeys-Dietz syndrome. This
      result suggests an increase in the mutation spectrum of Marfan-related disorders
      in China and possibly world-wide.

PMID- 20144265
TI  - Localization of cyclo-oxygenase-2 in human recurrent colorectal cancer.
AB  - AIM: The aim of this paper is to examine COX-2 expression in human recurrent
      colorectal carcinoma tissues using immunohistochemistry and quantative real-time
      PCR (qPCR). METHODS: Colon and rectal specimens were obtained from 26 patients
      with recurrent colorectal carcinomas. We examined COX-2 expression in human
      recurrent colorectal carcinoma tissues using immunohistochemistry and quantative
      real-time PCR (qPCR). RESULTS: In recurrent colorectal cancer a strong
      cytoplasmic and perinuclear staining of COX-2 was found. Moderate to strong
      immunosignals were detected in almost all of the carcinomas. We observed a strong
      specific staining of COX-2 in vascular endothelium. COX-2 immunoreactivity was
      also detected in stromal cells such as mononuclear cells, fibroblasts, and smooth
      muscle cells. The real-time PCR analyses demonstrated marked overexpression of
      the COX-2 gene in the cancer mucosa in concert with the immunohistochemistry
      data. CONCLUSION: We investigated COX-2 expression at the level of its protein as
      well as its messenger RNA in a series of recurrent colorectal cancers. These
      observations give additional information about the possibility that COX-2 could
      be involved in tumor promotion during colorectal cancer progression.

PMID- 20144267
TI  - State-Trait Anxiety Inventory (STAI) assessment of mothers with language delayed
      children.
AB  - OBJECTIVES: In this study, we evaluated the continuous and state anxiety levels
      of mothers with children with language delay. METHODS: The study group consisted
      of the mothers of 18 children with language delay. The control group consisted of
      the mothers of 29 healthy children without language delay. To gain data about
      mothers, a personal information form and Spielberger's State-Trait Anxiety
      Inventory (STAI) form were applied to determine continuous and state-trait
      anxiety levels. RESULTS: State anxiety levels in the study group were
      significantly higher (by Student t-test) than that of the control group. For
      continuous anxiety level, no statistically significant difference was determined
      between two groups. In the study group, higher education levels of mothers and
      their husbands were associated with lower levels of both continuous and state
      anxiety. CONCLUSION: In the majority of the group of mothers with language
      delayed children and even mothers of children with normal language development,
      there were high levels concern. Mothers' concerns and anxiety levels may decrease
      with increasing levels of their education levels. We recommend providing detailed
      information regarding language development to the families at all stages of the
      childs' training programme.

PMID- 20144268
TI  - The assessment of atherosclerosis on vascular structures in patients with acute
      coronary syndrome.
AB  - INTRODUCTION: Endothelial dysfunction plays a crucial role in the process of
      atherosclerotic diseases and has been accepted as an early stage of
      atherosclerosis. Carotid intima-media-thickness (CIMT) and flow-mediated
      dilatation (FMD) of the brachial artery have been recommended as noninvasive
      methods to assess endothelial structure and function. Angiographic properties of
      patients with acute coronary syndrome (ACS) are closely associated with
      cardiovascular events. In this study, we investigated the relation of
      atherosclerotic properties of coronary, brachial and carotid arteries with CIMT,
      FMD and coronary angiography in patients with ACS. METHODS: We enrolled 133
      patients who were diagnosed with ACS into this study. Exclusion criteria were
      known coronary artery disease, diabetes mellitus and hypertension. Coronary
      angiography, CIMT and FMD were measured in all patients. The numbers of major
      stenotic coronary vessels with > or = 50% or > or = 70% were defined as diseased
      vessel. Gensini score was used to evaluate the severity of atherosclerosis.
      Morphologic properties of stenotic lesion were defined. Cutoff levels were 7% for
      FMD and 0.9 mm for CIMT. RESULTS: Mean age was 59.7 + or - 11.8 years. FMD, CIMT
      and Gensini score were 8.3 + or - 5.9%, 0.80 + or - 0.19 mm and 7.8 + or - 3.5,
      respectively. Only 44% of patients with ACS had impaired FMD. Gensini score,
      number of diseased vessels and number of critical lesions were higher in patients
      with impaired FMD. (Gensini: 8.7 + or - 3.6 vs. 7.0 + or - 3.1, p = 0.009,
      diseased vessels: 2.7 + or - 0.4 vs. 2.3 + or - 0.7, p < 0.0001, critical
      lesions: 3.0 + or - 2.1 vs. 2.2 + or - 1.4, p = 0.02). Increased CIMT was found
      in only 33% of patients. Gensini score and number of diseased vessels were
      significantly higher in patients with increased CIMT. Significant but weak
      correlations were found between CIMT, FMD and angiographic severity of coronary
      atherosclerosis. Angiographic properties and lesion morphology were similar
      between CIMT and FMD groups. CONCLUSION: There appears to be a relationship
      between CIMT, FMD and severity of coronary atherosclerosis in patients with ACS.
      However, in patients with ACS, morphologic properties of stenotic lesions are not
      associated with CIMT and FMD in brachial artery.

PMID- 20144269
TI  - CD133(+) human pulmonary adenocarcinoma cells induce apoptosis of CD8(+) T cells
      by highly expressed galectin-3.
AB  - PURPOSE: To investigate the expression and function of Galectin-3 (Gal-3) in
      CD133(+) pulmonary adenocarcinoma. METHODS: CD133(+) pulmonary adenocarcinoma
      cells were separated by MACS from excised pulmonary adenocarcinoma specimens of
      11 patients. The percentage of CD133(+) cells in different cells population was
      determined by flow cytometry (FCM). Expression of Gal-3 in cancer cells was
      detected by Fluorescence Quantitation RT-PCR (FQRT-PCR) and Western blot whereas
      extracellular expression was detected by ELISA. CD133(+) cells were transfected
      with Gal-3 specific siRNA to explore the affects of Gal-3 inhibition on cancer
      cell growth and induction of CD8(+) T cell apoptosis. RESULTS: Cells expressing
      CD133 constituted 90% of the CD133(+) subpopulation after separation by MACS
      whereas they made up only 1.2% of the unsorted cell population. Expression of Gal
      3 was 1.24 fold, 1.5 fold and 2 fold higher in CD133(+) cells than in CD133(-)
      cells as detected by FQRT-PCR, Western blot and ELISA respectively (p < 0.05 for
      each). The supernatants of CD133(+) cells induced apoptosis of CD8(+) T cells to
      a greater degree (27.1+ or - 2.6%) compared with supernatants from CD133(-) cells
      (10.1 + or - 2.2%), and could be down-regulated by lactose, anti-galectin-3
      polyclonal antibody and Gal-3 siRNA. Downregulation of Gal-3 resulted in
      significant inhibition of cancer cell growth in vitro. CONCLUSION: Gal-3 is
      expressed at a relatively higher level in CD133(+) lung adenocarcinoma cells and
      could induce CD8(+) T cell apoptosis in vitro, both of which could be down
      regulated by Gal-3 siRNA. These findings indicate that Gal-3 may play an
      important role during oncogenesis, implying a potential therapeutic target for
      pulmonary adenocarcinoma.

PMID- 20144270
TI  - The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation
      in IgA nephropathy.
AB  - PURPOSE: IgA1 aberrant O-glycosylation is one of the main pathogenetic features
      of IgA nephropathy (IgAN). This study attempted to determine the role of
      C1GALT1C1 in aberrant IgA1 O-glycosylation induced by lipopolysaccharide (LPS)
      and identify potential therapeutic targets in IgAN. METHODS: Lymphocytes isolated
      from 22 patients with IgAN and 17 normal controls were cultured for 3 to 7 days
      with or without LPS and 5-azacytidine (5-AZA). Expression levels of C1GALT1C1
      mRNA and protein were measured by real-time PCR and Western blot analysis,
      respectively. Concentration of IgA1 and level of O-glycosylation were determined
      by ELISA and Vicia villosa (VV) lectin-binding assay. Correlation analysis was
      performed between the expression of C1GALT1C1 protein and IgA1 O-glycosylation.
      RESULTS: Lymphocytes from patients with IgAN secreted more IgA1 than that from
      normal controls after LPS stimulation (P=0.26, 0.002 and 0.005 on the 3rd, 5th
      and 7th day, respectively) which could be inhibited by 5-AZA (P=0.001, 0.025 and
      0.001 on the 3rd, 5th and 7th day, respectively). Moreover, LPS stimulation could
      obviously inhibit C1GALT1C1 expression in patients with IgAN (decreased by 71%,
      82% and 92% on the 3rd, 5th and 7th day, respectively; P < 0.001), and cause a
      significant decrease of IgA1 O-glycosylation compared with normal controls
      (P=0.004, 0.003 and 0.03 on the 3rd, 5th and 7th day, respectively). When 5-AZA
      was added, the level of C1GALT1C1 expression increased dramatically (1.98, 5.53
      and 8.97 times on the 3rd, 5th and 7th day, respectively; P < 0.001) along with
      an increase of IgA1 O-glycosylation (P=0.295, 0.09 and 0.003 on the 3rd, 5th and
      7th day, respectively). However, normal controls showed no significant change in
      C1GALT1C1 expression and IgA1 O-glycosylation after LPS stimulation (P > 0.05).
      CONCLUSION: LPS induced IgA1 aberrant O-glycosylation and suppressed C1GALT1C1
      expression in patients with IgAN. Upregulation of C1GALT1C1 expression by 5-AZA
      could reverse the IgA1 aberrant O-glycosylation. These results suggest that
      C1GALT1C1 may play a key role in the regulation of IgA1 O-glycosylation.

PMID- 20144271
TI  - Comparison of two oscillometric blood pressure monitors in subjects with atrial
      fibrillation.
AB  - OBJECTIVE: To compare blood pressure readings obtained with two commonly used
      oscillometric monitors: Omron HEM 711 AC (OM) and Welch-Allyn 52000 series
      NIBP/oximeter (WA) with mercury sphygmomanometers (Merc) in subjects with atrial
      fibrillation. METHODS: We recruited 51 hemodynamically stable subjects with
      atrial fibrillation. Fifty four subjects in normal sinus rhythm served as
      controls. Supine blood pressure readings in each arm were recorded simultaneously
      using one monitor and Merc. The second monitor then replaced the first and
      readings were repeated. Merc was then switched to the opposite arm, and both
      monitors retested. Apical heart rates were ascertained with a stethoscope. We
      used the averaged, same arm Merc readings as "gold standard". RESULTS: Automated
      blood pressure readings were obtained in all control subjects and in all but
      three of those with atrial fibrillation. Both monitors, and operators, noted a
      difference between apical and radial/brachial pulse rates: apical-recorded: Merc
      6.1 + or - 15.0; OM 5.5 + or - 13.7; WA 10.0 + or - 21.2 beats per minute. Both
      monitors were accurate in controls: over 90% of readings were within 10 mmHg of
      averaged Merc, and both achieved European Hypertension Society standards. In
      subjects with atrial fibrillation, about one quarter of all oscillometric
      readings differed from Merc by more than 10 mmHg. Both falsely high and falsely
      low readings occurred, some up to 30 mmHg. There was no relation between accuracy
      and heart rate. CONCLUSIONS: Single blood pressure readings, taken with
      oscillometric monitors in subjects with atrial fibrillation differ, often
      markedly, from those taken manually. Health care professionals should record
      multiple readings manually, using validated instruments when making therapeutic
      decisions.

PMID- 20144272
TI  - Association of an asporin repeat polymorphism with ankylosing spondylitis in Han
      Chinese population: a case-control study.
AB  - OBJECTIVE: To investigate the role of a functional polymorphism consisting of an
      aspartic acid (D) repeat located in the asporin gene (ASPN) gene in the
      susceptibility to and clinical outcome of ankylosing spondylitis (AS). METHODS: A
      total of 374 Chinese patients with ankylosing spondylitis and 421 controls of the
      same ethnic origin matched for age and sex were included in the study. The
      asporin D repeat polymorphism was genotyped by polymerase chain reaction with a
      fluorescent primer. RESULTS: Significant differences between AS patients and
      controls were detected in the distribution of the 7 alleles found in our
      population. D14 and D16 alleles were significantly over-represented in AS
      patients (D14, P=0.001, odds ratio (OR)=1.857, 95% confidence interval(CI) 1.27
      2.715; and D16, P < 0.0001, OR=2.605, 95% CI 1.75-3.879). D16 over-representation
      was more common in early-onset patients than in late-onset patients, although the
      difference did not reach significance (P= 0.071). CONCLUSION: The results support
      a role for an asporin D repeat polymorphism in the susceptibility to AS and an
      influence of this gene on the outcome of the disease. D14 and D16 allele variants
      of ASPN might be the susceptibility alleles for AS in the Han Chinese population,
      whereas the D13 allele variant may have a protective effect on the onset of AS.

PMID- 20144273
TI  - Scientific overview of the CSCI-CITAC 2009 conference.
AB  - From September 21st-23rd 2009, the Clinical Investigator Trainee Association of
      Canada - Association des cliniciens-chercheurs en formation du Canada (CITAC
      ACCFC) and the Canadian Society for Clinician Investigators (CSCI), held their
      annual conference in Ottawa. Participants included clinician investigators and
      trainees from across the country. The conference featured many excellent guest
      speakers including this year's recipient of the Henry G. Friesen International
      Prize in Health Research, Sir John Bell. There were several forums focusing on
      professional development, with topics such as "sustaining the clinician
      investigator in Canada", "succeeding as a clinician investigator", and
      "collaborating internationally with MD+ trainees", alongside networking
      opportunities to help establish relationships with potential mentors and
      collaborators. Further, the CSCI-CITAC annual conference featured some of the
      cutting edge research that MD+ trainees throughout Canada are engaged in.
      Trainees presented their research either at the Young Investigators Forum poster
      session or at the oral plenary. This scientific overview aims to highlight some
      of the research presented by trainees at the annual conference. The broad themes
      of scientific interest included topics from both basic science and clinical
      research. In this article, we summarize some of the major research questions that
      are being investigated by clinician-investigator trainees in the following areas:
      neurological sciences, cell biology, medicine, immunology, obstetrics,
      gynecology, neonatology, orthopedics, rheumatology, and public health.

PMID- 20144275
TI  - A sweetened beverage tax is needed to combat the obesity epidemicas well as
      related absenteeism and presenteeism.

PMID- 20144276
TI  - Variation in the frequency of hemoglobin A1c (HbA1c) testing: population studies
      used to assess compliance with clinical practice guidelines and use of HbA1c to
      screen for diabetes.
AB  - BACKGROUND: The volume of hemoglobin A1c (HbA1c) testing has increased
      dramatically over the past decade and few studies have attempted to determine how
      the test is used. The goals of this study were to evaluate the frequency of HbA1c
      testing in regional populations to assess the extent of screening for diabetes
      and to determine if the HbA1c testing intervals of known diabetic patients were
      consistent with clinical practice guidelines. METHODS: Two years of HbA1c results
      were extracted from laboratory information systems in four regions of the
      province of Alberta that represent urban, mixed urban-rural, and rural
      populations. HbA1c testing frequencies and the proportions of nondiabetic
      patients undergoing HbA1c tests were derived. RESULTS: Approximately 60% of HbA1c
      tests in each region were done on patients who had only a single test during the
      2-year interval. Testing of nondiabetic patients accounted for 24% of HbA1c tests
      and varied by region. While the cumulative frequency distributions of HbA1c test
      intervals resembled each other, detailed analyses of the frequency distributions
      depicted broad multimodal peaks and regional variations that suggest a great deal
      of heterogeneity among practices. The most common HbA1c testing interval was 3
      months +/- 3 weeks in each region and is consistent with the 3-month test
      interval target in a clinical practice guideline. CONCLUSIONS: HbA1c testing is
      being performed on a substantial proportion of nondiabetic patients. On average,
      patients with diabetes in Alberta receive 1.5 HbA1c tests per year. However, we
      observed regional differences in the frequency of testing and variation in
      compliance with clinical practice guidelines.

PMID- 20144277
TI  - Hemoglobin A1c point-of-care assays; a new world with a lot of consequences!
AB  - BACKGROUND: Point-of-care instruments for the measurement of hemoglobin A1c
      (HbA1c) may improve the glycemic control of people with diabetes by providing a
      rapid result if the performance of the instruments used is acceptable. A 0.5%
      HbA1c difference between successive results is considered a clinically relevant
      change. With this in mind, the In2it from Bio-Rad and the DCA Vantage from
      Siemens were evaluated according to Clinical and Laboratory Standards Institute
      (CLSI) protocols. METHODS: The CLSI protocols EP-5 and EP-9 were applied to
      investigate precision, accuracy, and bias. The bias was compared with three
      certified secondary reference measurement procedures. Differences between
      capillary and venous blood were investigated by an end-user group consisting of
      nurse practitioners at a diabetes care center. RESULTS: At HbA1c levels of 5.1
      and 11.2%, total coefficients of variation (CV) for the In2it were 4.9 and 3.3%,
      respectively, and for the DCA Vantage were 1.7 to 1.8% and 3.7 to 5.5% depending
      on the lot number of the cartridges. Method comparisons showed significant lot
      number-dependent results for the In2it and the DCA Vantage compared with the
      three reference methods. No overall difference was observed between capillary and
      venous blood for both methods. CONCLUSION: Performance results of the In2it and
      the DCA Vantage showed variable and lot number-dependent results. To maintain the
      interlaboratory CV of 5% for HbA1c, the Clinical Laboratory Improvement
      Amendments rules for waived point-of-care instruments should be revised. An
      obligation for participating in external quality schemes and taking adequate
      action should be considered for POC instruments that perform poorly.

PMID- 20144278
TI  - Use of serial patient hemoglobin A1c differences to determine long-term
      imprecision of immunoassay and high-performance liquid chromatography analyzers.
AB  - BACKGROUND: The quality of the HbA1c assay is inversely proportional to the
      variation of the assay. Most published measures of HbA1c variation are limited by
      the data collection period, the statistical treatment of outliers, and even the
      noncommutability of the products used to generate the variation measurements. We
      have used an alternate approach to derive HbA1c variation, using serial patient
      data. METHODS: HbA1c measurements of outpatient blood sample pairs drawn within
      30 days of each other were made on three different immunoassay systems: the Roche
      INTEGRA 700, the Roche INTEGRA 400, and the Dade Dimension RxL; and two high
      performance liquid chromatography assays: the Tosoh G7 and the Tosoh 2.2+. The
      standard deviation of duplicates was calculated for the following time intervals:
      1 to 3 days, 4 to 6 days, 7 to 9 days,.., 28 to 30 days. These intra-individual
      variations were then plotted; extrapolation to time zero yields the long term
      total random error which consists of both analytic and pre-analytic error. Data
      collection periods were usually 2 years. RESULTS: At the mean HbA1cs of 7.08%,
      7.14%, 7.20%, 6.96%, and 7.51% for populations tested on the Roche INTEGRA 700,
      Roche INTEGRA 400, Dade Dimension RxL, Tosoh 2.2+, and Tosoh G7, respectively,
      the total analytic imprecisions (coefficient of variation) were 2.56%, 2.29%,
      2.25%, 1.66%, and 1.14%, respectively. CONCLUSION: Assessment of the HbA1c long
      term total imprecisions shows that while the three immunoassay systems are
      acceptable, the Tosoh HbA1c analyzers demonstrate superior analytic performance.

PMID- 20144279
TI  - The correlation of hemoglobin A1c to blood glucose.
AB  - The understanding that hemoglobin A1c (HbA1c) represents the average blood
      glucose level of patients over the previous 120 days underlies the current
      management of diabetes. Even in making such a statement, we speak of "average
      blood glucose" as though "blood glucose" were itself a simple idea. When we
      consider all the blood glucose forms-arterial versus venous versus capillary,
      whole blood versus serum versus fluoride-preserved plasma, fasting versus
      nonfasting-we can start to see that this is not a simple issue. Nevertheless, it
      seems as though HbA1c correlates to any single glucose measurement. Having more
      than one measurement and taking those measurements in the preceding month
      improves the correlation further. In particular, by having glucose measurements
      that reflect both the relatively lower overnight glucose levels and measurements
      that reflect the postprandial peaks improves not only our ability to manage
      diabetes patients, but also our understanding of how HbA1c levels are determined.
      Modern continuous glucose monitoring (CGM) devices may take thousands of glucose
      results over a week. Several studies have shown that CGM glucose averages account
      for the vast proportion of the variation of HbA1c. The ability to relate HbA1c to
      average glucose may become a popular method for reporting HbA1c, eliminating
      current concerns regarding differences in HbA1c standardization. Hemoglobin A1c
      expressed as an average glucose may be more understandable to patients and
      improve not only their understanding, but also their ability to improve their
      diabetes management.

PMID- 20144281
TI  - A review of variant hemoglobins interfering with hemoglobin A1c measurement.
AB  - Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in
      people with diabetes mellitus, as HbA1c is related directly to risks for diabetic
      complications. The accuracy of HbA1c methods can be affected adversely by the
      presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin
      (HbF). The effect of each variant or elevated HbF must be examined with each
      specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and
      HbD. All of these Hb variants have single amino acid substitutions in the Hb beta
      chain. HbF is the major hemoglobin during intrauterine life; by the end of the
      first year, HbF falls to values close to adult levels of approximately 1%.
      However, elevated HbF levels can occur in certain pathologic conditions or with
      hereditary persistence of fetal hemoglobin. In a series of publications over the
      past several years, the effects of these four most common Hb variants and
      elevated HbF have been described. There are clinically significant interferences
      with some methods for each of these variants. A summary is given showing which
      methods are affected by the presence of the heterozygous variants S, E, C, and D
      and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high
      performance liquid chromatography, boronate affinity, other) with an indication
      of whether the result is artificially increased or decreased by the presence of a
      Hb variant. Laboratorians should be aware of the limitations of their method with
      respect to these interferences.

PMID- 20144280
TI  - A review of the challenge in measuring hemoglobin A1c.
AB  - The attraction of the simple biochemical concept combined with a clinical
      requirement for a long-term marker of glycolic control in diabetes has made
      hemoglobin A1c (HbA1c) one of the most important assays undertaken in the medical
      laboratory. The diversity in the biochemistry of glycation, clinical
      requirements, and management demands has resulted in a broad range of methods
      being developed since HbA1c was described in the late 1960s. A range of analytic
      principles are used for the measurement of HbA1c. The charge difference between
      hemoglobin A0 and HbA1c has been widely utilized to separate these two fractions,
      most notably found these days in ion-exchange high-performance liquid
      chromatography systems; the difference in molecular structure (affinity
      chromatography and immunochemical methods) are becoming widely available.
      Different results found in different laboratories using a variety of HbA1c
      analyses resulted in the need for standardization, most notably in the United
      States, Japan, and Sweden. Designated comparison methods are now located in these
      three countries, but as they are arbitrarily chosen and have differences in
      specificity, results of these methods and the reference values and action limits
      of the methods differ and only harmonized HbA1c in specific geographic areas. A
      reference measurement system within the concept of metrological traceability is
      now globally accepted as the only valid analytic anchor. However, there is still
      discussion over the units to be reported. The consensus statement of the
      International Federation of Clinical Chemistry (IFCC), the American Diabetes
      Association, the International Diabetes Federation, and the European Association
      for the Study of Diabetes suggests reporting HbA1c in IFCC units (mmol/mol),
      National Glycohemoglobin Standardization Program units (%), and estimated average
      glucose (either in mg/dl or mmol/liter). The implementation of this consensus
      statement raised new questions, to be answered in a concerted action of
      clinicians, biochemists, external quality assessment organizers, patient groups,
      and manufacturers.

PMID- 20144282
TI  - Beyond health information technology: critical factors necessary for effective
      diabetes disease management.
AB  - BACKGROUND: Electronic health records (EHRs) have been implemented throughout the
      United States with varying degrees of success. Past EHR implementation
      experiences can inform health systems planning to initiate new or expand existing
      EHR systems. Key "critical success factors," e.g., use of disease registries,
      workflow integration, and real-time clinical guideline support, have been
      identified but not fully tested in practice. METHODS: A pre/postintervention
      cohort analysis was conducted on 495 adult patients selected randomly from a
      diabetes registry and followed for 6 years. Two intervention phases were
      evaluated: a "low-dose" period targeting primary care provider (PCP) and patient
      education followed by a "high-dose" EHR diabetes management implementation
      period, including a diabetes disease registry and office workflow changes, e.g.,
      diabetes patient preidentification to facilitate real-time diabetes preventive
      care, disease management, and patient education. RESULTS: Across baseline, "low
      dose," and "high-dose" postintervention periods, a significantly greater
      proportion of patients (a) achieved American Diabetes Association (ADA)
      guidelines for control of blood pressure (26.9 to 33.1 to 43.9%), glycosylated
      hemoglobin (48.5 to 57.5 to 66.8%), and low-density lipoprotein cholesterol (33.1
      to 44.4 to 56.6%) and (b) received recommended preventive eye (26.2 to 36.4 to
      58%), foot (23.4 to 40.3 to 66.9%), and renal (38.5 to 53.9 to 71%) examinations
      or screens. CONCLUSIONS: Implementation of a fully functional, specialized EHR
      combined with tailored office workflow process changes was associated with
      increased adherence to ADA guidelines, including risk factor control, by PCPs and
      their patients with diabetes. Incorporation of previously identified "critical
      success factors" potentially contributed to the success of the program, as did
      use of a two-phase approach.

PMID- 20144283
TI  - Communication plays a critical role in web-based monitoring.
AB  - BACKGROUND: Patient-health care practitioner (HCP) interaction via a Web-based
      diabetes management system may increase patient monitoring of their blood glucose
      (BG) levels. METHODS: A three-center, nonrandomized, prospective feasibility
      study of 109 Native Americans with poorly controlled type 1 diabetes mellitus and
      type 2 diabetes mellitus were recruited from Alabama, Idaho, and Arizona. The
      study intervention included the use of a Web-based diabetes management
      application (MyCareTeam) that allowed timely interaction between patients and
      HCPs. Information about diabetes, nutrition, and exercise was also available.
      Finally, patients were able to provide BG readings to their HCP via the
      MyCareTeam system. RESULTS: As a result, 59.6% of the patients sent one or more
      messages to their HCP, 92.67% received one or more messages from their HCP, and
      78.89% received one or more person-centered messages from their HCP.
      Additionally, the number of times a patient logged into the system and the
      frequency with which they tested their blood sugar were correlated with (a) the
      number of messages sent to their HCP, (b) the total number of messages received
      from their HCP, and (c) the number of person-centered messages received from
      their HCP. Thus patients who sent more messages also tested their BG more
      frequently, as measured by the number of BG readings uploaded from their meter to
      the MyCareTeam database. Person-centered messages seem to be particularly
      important to motivating the patient to monitor their BG levels and use the Web
      based system. CONCLUSIONS: These results suggest that patient-HCP interaction
      and, in particular, more personalized interactions increases patient frequency of
      BG monitoring.

PMID- 20144284
TI  - TheClinical Research Tool: a high-performance microdialysis-based system for
      reliably measuring interstitial fluid glucose concentration.
AB  - BACKGROUND: A novel microdialysis-based continuous glucose monitoring system, the
      so-called Clinical Research Tool (CRT), is presented. The CRT was designed
      exclusively for investigational use to offer high analytical accuracy and
      reliability. The CRT was built to avoid signal artifacts due to catheter
      clogging, flow obstruction by air bubbles, and flow variation caused by
      inconstant pumping. For differentiation between physiological events and system
      artifacts, the sensor current, counter electrode and polarization voltage,
      battery voltage, sensor temperature, and flow rate are recorded at a rate of 1
      Hz. METHOD: In vitro characterization with buffered glucose solutions (c(glucose)
      = 0 - 26 x 10(-3) mol liter(-1)) over 120 h yielded a mean absolute relative
      error (MARE) of 2.9 +/- 0.9% and a recorded mean flow rate of 330 +/- 48 nl/min
      with periodic flow rate variation amounting to 24 +/- 7%. The first 120 h in vivo
      testing was conducted with five type 1 diabetes subjects wearing two systems
      each. A mean flow rate of 350 +/- 59 nl/min and a periodic variation of 22 +/- 6%
      were recorded. RESULTS: Utilizing 3 blood glucose measurements per day and a
      physical lag time of 1980 s, retrospective calibration of the 10 in vivo
      experiments yielded a MARE value of 12.4 +/- 5.7. Clarke error grid analysis
      resulted in 81.0%, 16.6%, 0.8%, 1.6%, and 0% in regions A, B, C, D, and E,
      respectively. CONCLUSION: The CRT demonstrates exceptional reliability of system
      operation and very good measurement performance. The ability to differentiate
      between artifacts and physiological effects suggests the use of the CRT as a
      reference tool in clinical investigations.

PMID- 20144285
TI  - Cleveland Clinic cardiovascular intensive care unit insulin conversion protocol.
AB  - BACKGROUND: The importance of near-normal blood glucose in the immediate
      postoperative period is generally accepted and is best achieved in the
      perioperative period with a constant intravenous (IV) infusion of insulin. This
      requires intensive nursing only achievable in an intensive care unit (ICU)
      setting. Glucose management after transfer to a regular nursing floor (RNF) has
      not been studied systematically. In August 2006, the Cleveland Clinic began using
      long-acting insulin glargine as the insulin infusion was terminated in the ICU.
      METHODS: This prospective analysis examined all patients receiving IV insulin
      infusion after cardiothoracic surgery in a 1 month period. The analyses evaluated
      the safety and efficacy of a protocol using a transition to subcutaneous insulin
      glargine of 50% of the calculated 24 h requirement at the end of the ICU insulin
      infusion protocol in preparation for transfer to the RNF. RESULTS: Only 1 patient
      in 99 developed hypoglycemia, and no patient suffered severe hypoglycemia
      (glucose < 40 mg/dl), while the majority (70%) had euglycemia (glucose between 70
      and 150 mg/dl). CONCLUSIONS: This approach was both safe-as there was very little
      hypoglycemia (1 patient in 99)-and effective, as blood sugar was well controlled
      in most subjects. Efficacy for achieving euglycemia was 70%. Efficacy was likely
      reduced because of the upper limit of insulin glargine dosage imposed by some
      providers as a safety consideration. Although there was a physician option to
      override, the maximum protocol dose of 30 U was rarely exceeded, leading to
      inadequate dosing in some subjects who required high insulin infusion rates in
      the ICU.

PMID- 20144286
TI  - Clinical update on optimal prandial insulin dosing using a refined run-to-run
      control algorithm.
AB  - BACKGROUND: This article provides a clinical update using a novel run-to-run
      algorithm to optimize prandial insulin dosing based on sparse glucose
      measurements from the previous day's meals. The objective was to use a refined
      run-to-run algorithm to calculate prandial insulin-to-carbohydrate ratios (I:CHO)
      for meals of variable carbohydrate content in subjects with type 1 diabetes
      (T1DM). METHOD: The open-labeled, nonrandomized study took place over a 6-week
      period in a nonprofit research center. Nine subjects with T1DM using continuous
      subcutaneous insulin infusion participated. Basal insulin rates were optimized
      using continuous glucose monitoring, with a target fasting blood glucose of 90
      mg/dl. Subjects monitored blood glucose concentration at the beginning of the
      meal and at 60 and 120 minutes after the start of the meal. They were instructed
      to start meals with blood glucose levels between 70 and 130 mg/dl. Subjects were
      contacted daily to collect data for the previous 24-hour period and to give them
      the physician-approved, algorithm-derived I:CHO ratios for the next 24 hours.
      Subjects calculated the amount of the insulin bolus for each meal based on the
      corresponding I:CHO and their estimate of the meal's carbohydrate content. One-
      and 2-hour postprandial glucose concentrations served as the main outcome
      measures. RESULTS: The mean 1-hour postprandial blood glucose level was 104 +/-
      19 mg/dl. The 2-hour postprandial levels (96.5 +/- 18 mg/dl) approached the
      preprandial levels (90.1 +/- 13 mg/dl). CONCLUSIONS: Run-to-run algorithms are
      able to improve postprandial blood glucose levels in subjects with T1DM.

PMID- 20144287
TI  - Can technology improve adherence to long-term therapies?
AB  - BACKGROUND: Therapeutic nonadherence is defined as the lack of equivalence
      between the behavior of the patients and their prescribed medical treatment.
      Consequences of nonadherence include not only health outcomes, but also cost
      saving. Thus, this issue gets paramount importance in contemporary medicine.
      METHOD: The aim of this article is to discuss the relationships between
      technology and adherence by asking the following three questions. (1) How can
      technology be used to monitor patient adherence? (2) Considering the mechanisms
      of nonadherence in chronic diseases, is there room for technology in
      interventions aimed to improve patient adherence? (3) What about adherence to
      technology in diabetes care? RESULTS AND CONCLUSION: Technology may help improve
      adherence to long-term therapies by (1) giving a concrete representation of
      adherence rewards, (2) overcoming immediate obstacles to adherence, such as the
      fear of hypoglycemia, and (3) providing an opportunity for patient-doctor
      conversations. This assumes, however, that both the patient and the doctor are
      convinced that technologies are useful.

PMID- 20144288
TI  - Value of self-monitoring blood glucose pattern analysis in improving diabetes
      outcomes.
AB  - Self-monitoring of blood glucose (SMBG) is an important adjunct to hemoglobin A1c
      (HbA1c) testing. This action can distinguish between fasting, preprandial, and
      postprandial hyperglycemia; detect glycemic excursions; identify and monitor
      resolution of hypoglycemia; and provide immediate feedback to patients about the
      effect of food choices, activity, and medication on glycemic control. Pattern
      analysis is a systematic approach to identifying glycemic patterns within SMBG
      data and then taking appropriate action based upon those results. The use of
      pattern analysis involves: (1) establishing pre- and postprandial glucose
      targets; (2) obtaining data on glucose levels, carbohydrate intake, medication
      administration (type, dosages, timing), activity levels and physical/emotional
      stress; (3) analyzing data to identify patterns of glycemic excursions, assessing
      any influential factors, and implementing appropriate action(s); and (4)
      performing ongoing SMBG to assess the impact of any therapeutic changes made.
      Computer-based and paper-based data collection and management tools can be
      developed to perform pattern analysis for identifying patterns in SMBG data. This
      approach to interpreting SMBG data facilitates rational therapeutic adjustments
      in response to this information. Pattern analysis of SMBG data can be of equal or
      greater value than measurement of HbA1c levels.

PMID- 20144289
TI  - EyePACS: an adaptable telemedicine system for diabetic retinopathy screening.
AB  - BACKGROUND: Annual retinal screening of patients with diabetes is the standard
      clinical practice to prevent visual impairment and blindness from diabetic
      retinopathy. Telemedicine-based diabetic retinopathy screening (DRS) in primary
      care settings can effectively detect sight-threatening retinopathy and
      significantly increase compliance with annual retinal exams. EyePACS is a license
      free Web-based DRS system designed to simplify the process of image capture,
      transmission, and review. The system provides a flexible platform for
      collaboration among clinicians about diabetic retinopathy. METHODS: Primary
      clinic personnel (i.e., nursing, technical, or administrative staff) are trained
      and certified by the EyePACS program to acquire retinal images from standard
      digital retinal cameras. Relevant clinical data and eight high-resolution images
      per patient (two external and six retinal images) are encrypted and transmitted
      to a secure Internet server, using a standard computer and Web browser. Images
      are then interpreted by certified EyePACS reviewers or local eye care providers
      who are certified through the EyePACS Retinopathy Grading System. Reports
      indicating retinopathy level and referral recommendations are transmitted back to
      primary care providers through the EyePACS Web site or through interfaces between
      EyePACS and Health Level 7-compliant electronic medical records or chronic
      disease registries. RESULTS: The pilot phase of the EyePACS DRS program in
      California (2005-2006) recorded 3562 encounters. Since 2006, EyePACS has been
      expanded to over 120 primary care sites throughout California and elsewhere
      recording over 34,000 DRSs. The overall rate of referral is 8.21% for sight
      threatening retinopathy and 7.83% for other conditions (e.g., cataract and
      glaucoma). CONCLUSION: The use of license-free Web-based software, standard
      interfaces, and flexible protocols has allowed primary care providers to adopt
      retinopathy screening with minimal effort and resources.

PMID- 20144290
TI  - Noninvasive ultrasonic glucose sensing with large pigs (approximately 200 pounds)
      using a lightweight cymbal transducer array and biosensors.
AB  - BACKGROUND: To prevent complications in diabetes, the proper management of blood
      glucose levels is essential. Since conventional glucose meters require pricking
      fingers or other areas of the skin, a noninvasive method for monitoring blood
      glucose levels is desired. Using a lightweight cymbal transducer array, this
      study was conducted to noninvasively determine the glucose levels of pigs having
      a similar size to humans. METHOD: In vivo experiments using eight pigs
      (approximately 200 pounds) were performed in five groups. A cymbal array with
      four biosensors was attached to the axillary area of the pig. The array was
      operated at 20 kHz at special peak-temporal peak intensity (I(sptp)) equal to 50
      or 100 mW/cm(2) for 5, 10, or 20 minutes. After the ultrasound exposure, glucose
      concentrations of the interstitial fluid were determined using biosensors. For
      comparison, glucose levels of blood samples collected from the ear vein were
      measured by a commercial glucose meter. RESULT: In comparison, glucose levels
      determined by a cymbal array and biosensor system were close to those measured by
      a glucose meter. After a 20-minute ultrasound exposure at I(sptp) = 100 mW/cm(2),
      the average glucose level determined by the ultrasound system was 175 +/- 7
      mg/dl, which is close to 166 +/- 5 mg/dl measured by the glucose meter.
      CONCLUSION: Results indicate the feasibility of using a cymbal array for
      noninvasive glucose sensing on pigs having a similar size to humans. Further
      studies on the ultrasound conditions, such as frequency, intensity, and exposure
      time, will be continued for effective glucose sensing.

PMID- 20144291
TI  - Prescription checking device promises to resolve intractable hypoglycemia.
AB  - BACKGROUND: Satisfactory glycemic control, meeting American Diabetes Association
      recommendations, is often accompanied by unsatisfactory hypoglycemia. The
      converse is also true. We hypothesize that this diabetes treatment dilemma may be
      resolved by repeated, objective, prescription checks. To do this, a new, two-part
      device has been developed. It includes a personal diabetes database for the
      patient and a built-in diabetes prescription checker for the provider. Its goals
      are to enhance diabetes education and improve patient care. RESEARCH DESIGN AND
      METHODS: The device includes a database and supporting software, all contained in
      a standard USB flash drive. Using the medical prescription, body weight, and
      recent self-monitored blood glucose (SMBG) data, prescription checks can be done
      at any time. To demonstrate the device's capabilities, an observational study was
      performed using data from 11 patients with type 1 diabetes mellitus, on
      intensified therapy, with a mean glycated hemoglobin A1c <7%, and who all
      suffered intractable hypoglycemia. Patients had performed SMBG contours on
      successive days at monthly intervals. Each contour included pre- and postmeal as
      well as bedtime measurements. The replicated contours were used to predict the
      patient's glycemic profile each month. Applying a built-in simulator to each
      profile, changes in the prescription were explored that were consistent with
      reducing the recalcitrant hypoglycemia. RESULTS: A total of 110 glycemic profiles
      containing 822 profile points were explored. Of these profile points, 351 (43%)
      showed risks of hypoglycemia, whereas 385 (47%) fell outside desired ranges. With
      the simulated changes in the prescription, the predicted risks of hypoglycemia
      were reduced 2.5-fold with insignificant increases predicted in hemoglobin A1c
      levels of +0.6 +/- 0.9%. CONCLUSIONS: A novel support tool for diabetes promises
      to resolve the diabetes treatment dilemma. Supporting the patient, it improves
      self-management. Supporting the provider, it reviews the medical prescription in
      light of objective outcomes and formalizes interventions for maximum safety and
      efficacy.

PMID- 20144292
TI  - Analysis of the performance of the software/hardware product MyDiaBase+RxChecker
      for assessing treatment regimens.
AB  - In 2008, the Action to Control Cardiovascular Risk in Diabetes trial was halted
      due to an unexpected number of deaths in the intensive treatment group (aiming
      for hemoglobin A1c levels less than 6%). Hypoglycemic episodes were thought by
      some to be a contributing cause, underscoring again the challenge of maintaining
      tight control while avoiding dangerous excursions into hypoglycemic territory.
      Albisser and colleagues present a set of articles in this issue of Journal of
      Diabetes Science and Technology that describe a clinical product developed
      specifically for this timeless clinical conundrum.

PMID- 20144293
TI  - Safety constraints in an artificial pancreatic beta cell: an implementation of
      model predictive control with insulin on board.
AB  - BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by the destruction
      of pancreatic beta cells, resulting in the inability to produce sufficient
      insulin to maintain normoglycemia. As a result, people with T1DM depend on
      exogenous insulin that is given either by multiple daily injections or by an
      insulin pump to control their blood glucose. A challenging task is to design the
      next step in T1DM therapy: a fully automated insulin delivery system consisting
      of an artificial pancreatic beta cell that shall provide both safe and effective
      therapy. The core of such a system is a control algorithm that calculates the
      insulin dose based on automated glucose measurements. METHODS: A model predictive
      control (MPC) algorithm was designed to control glycemia by controlling exogenous
      insulin delivery. The MPC algorithm contained a dynamic safety constraint,
      insulin on board (IOB), which incorporated the clinical values of correction
      factor and insulin-to-carbohydrate ratio along with estimated insulin action
      decay curves as part of the optimal control solution. RESULTS: The results
      emphasized the ability of the IOB constraint to significantly improve the
      glucose/insulin control trajectories in the presence of aggressive control
      actions. The simulation results indicated that 50% of the simulations conducted
      without the IOB constraint resulted in hypoglycemic events, compared to 10% of
      the simulations that included the IOB constraint. CONCLUSIONS: Achieving both
      efficacy and safety in an artificial pancreatic beta cell calls for an IOB safety
      constraint that is able to override aggressive control moves (large insulin
      doses), thereby minimizing the risk of hypoglycemia.

PMID- 20144294
TI  - Technosphere insulin: defining the role of Technosphere particles at the cellular
      level.
AB  - BACKGROUND: Technosphere Insulin (TI) is a novel inhalation powder for the
      treatment of diabetes mellitus. Technosphere Insulin delivers insulin with an
      ultra rapid pharmacokinetic profile that is distinctly different from all other
      insulin products but similar to natural insulin release. Such rapid absorption is
      often associated with penetration enhancers that disrupt cellular integrity.
      METHODS: Technosphere Insulin was compared to a panel of known penetration
      enhancers in vitro using the Calu-3 lung cell line to investigate the effects of
      TI on insulin transport. RESULTS: Measures of tight junction integrity such as
      transepithelial electrical resistance, Lucifer yellow permeability, and F-actin
      staining patterns were all unaffected by TI. Cell viability and plasma membrane
      integrity were also not affected by TI. In contrast, cells treated with
      comparable (or lower) concentrations of penetration enhancers showed elevated
      Lucifer yellow permeability, disruption of the F-actin network, reduced cell
      viability, and compromised plasma membranes. CONCLUSIONS: These results
      demonstrate that TI is not cytotoxic in an in vitro human lung cell model and
      does not function as a penetration enhancer. Furthermore, TI does not appear to
      affect the transport of insulin across cellular barriers.

PMID- 20144295
TI  - A cell-based approach for diabetes treatment using engineered non-beta cells.
AB  - BACKGROUND: Implantation of insulin-secreting cells has the potential to provide
      tight glycemic regulation in diabetic subjects. Implantation of cadaveric human
      islets in immunosuppressed human patients is currently applied at a very small
      scale. To overcome the limitations of tissue availability and recipient
      immunosuppression, encapsulation of nonautologous cells and use of potentially
      autologous nonislet cells, the latter engineered for insulin secretion, are being
      pursued. This article reports on recent findings with the implantation of tissue
      constructs containing enteroendocrine cells stably expressing recombinant insulin
      in diabetic mice. The concept of a dual recombinant hepatic and enteroendocrine
      cell system, which may better approximate the secretory response of islets, is
      discussed. METHODS: Mouse GLUTag-INS cells engineered to secrete human insulin
      were developed and incorporated in tissue constructs as reported previously.
      Constructs were implanted intraperitoneally in diabetic mice, and blood glucose
      levels, animal weights, and plasma insulin levels were measured at various time
      points. RESULTS: GLUTag-INS-containing tissue constructs secreted insulin
      preimplantation and postexplantation, and human insulin was detected in the
      plasma of diabetic mice. However, normoglycemia was not restored. CONCLUSIONS: A
      variety of cell types and of encapsulation methods to enhance immune acceptance
      of insulin-secreting grafts are being pursued. Recombinant enteroendocrine cells
      show promise, but it is likely that they need to be combined with recombinant
      hepatic cells to achieve glycemic normalization.

PMID- 20144296
TI  - Oral insulin: the rationale for this approach and current developments.
AB  - Insulin remains the most effective and durable hypoglycemic agent for the
      treatment of diabetes. The addition of an effective oral insulin dosage form to
      the antidiabetes armamentarium may have significant benefits in terms of
      fostering compliance and adherence among patients, as well as physiologic
      advantages due to the fact that such a dosage form replicates the natural route
      of insulin secretion and absorption through the portal vein and targets the liver
      directly. Several companies have developed technological platforms that protect
      polypeptides and proteins from enzymatic hydrolysis, enable their transport
      across the epithelial lining, and promote their absorption from the
      gastrointestinal tract. A review of the potential physiological rationale and
      advantages, as well as of current pertinent technologies used specifically with
      insulin, is herewith provided.

PMID- 20144297
TI  - Oral insulin and buccal insulin: a critical reappraisal.
AB  - Despite the availability of modern insulin injection devices with needles that
      are so sharp and thin that practically no injection pain takes place, it is still
      the dream of patients with diabetes to, for example, swallow a tablet with
      insulin. This is not associated with any pain and would allow more discretion.
      Therefore, availability of oral insulin would not only ease insulin therapy, it
      would certainly increase compliance. However, despite numerous attempts to
      develop such a "tablet" in the past 85 years, still no oral insulin is
      commercially available. Buccal insulin is currently in the last stages of
      clinical development by one company and might become available in the United
      States and Europe in the coming years (it is already on the market in some other
      countries). The aim of this review is to critically describe the different
      approaches that are currently under development. Optimal coverage of prandial
      insulin requirements is the aim with both routes of insulin administration (at
      least with most approaches). The speed of onset of metabolic effect seen with
      some oral insulin approaches is rapid, but absorption appears to be lower when
      the tablet is taken immediately prior to a meal. With all approaches,
      considerable amounts of insulin have to be applied in order to induce
      therapeutically relevant increases in the metabolic effect because of the low
      relative biopotency of buccal insulin. Unfortunately, the number of publications
      about clinical-experimental and clinical studies is surprisingly low. In
      addition, there is no study published in which the variability of the metabolic
      effect induced (with and without a meal) was studied adequately. In summary,
      after the failure of inhaled insulin, oral insulin and buccal insulin are hot
      candidates to come to the market as the next alternative routes of insulin
      administration.

PMID- 20144299
TI  - An interview about telemedicine with John Oxendine, Georgia Insurance and Fire
      Commissioner, and Paula Guy, R.N., chief executive officer of the Georgia
      Partnership for Telehealth. Interview by David C. Klonoff, Jeffrey I. Joseph, Ron
      Poropatich and Mark True.

PMID- 20144298
TI  - Review of fructosyl amino acid oxidase engineering research: a glimpse into the
      future of hemoglobin A1c biosensing.
AB  - Glycated proteins, particularly glycated hemoglobin A1c, are important markers
      for assessing the effectiveness of diabetes treatment. Convenient and
      reproducible assay systems based on the enzyme fructosyl amino acid oxidase
      (FAOD) have become attractive alternatives to conventional detection methods. We
      review the available FAOD-based assays for measurement of glycated proteins as
      well as the recent advances and future direction of FAOD research. Future
      research is expected to lead to the next generation of convenient, simple, and
      economical sensors for glycated protein, ideally suited for point-of-care
      treatment and self-monitoring applications.

PMID- 20144300
TI  - Data mining technologies for blood glucose and diabetes management.
AB  - Data mining is the process of selecting, exploring, and modeling large amounts of
      data to discover unknown patterns or relationships useful to the data analyst.
      This article describes applications of data mining for the analysis of blood
      glucose and diabetes mellitus data. The diabetes management context is
      particularly well suited to a data mining approach. The availability of
      electronic health records and monitoring facilities, including telemedicine
      programs, is leading to accumulating huge data sets that are accessible to
      physicians, practitioners, and health care decision makers. Moreover, because
      diabetes is a lifelong disease, even data available for an individual patient may
      be massive and difficult to interpret. Finally, the capability of interpreting
      blood glucose readings is important not only in diabetes monitoring but also when
      monitoring patients in intensive care units. This article describes and
      illustrates work that has been carried out in our institutions in two areas in
      which data mining has a significant potential utility to researchers and clinical
      practitioners: analysis of (i) blood glucose home monitoring data of diabetes
      mellitus patients and (ii) blood glucose monitoring data from hospitalized
      intensive care unit patients.

PMID- 20144301
TI  - Are current insulin pumps accessible to blind and visually impaired people?
AB  - BACKGROUND: In 2004, Uslan and colleagues determined that insulin pumps (IPs) on
      the market were largely inaccessible to blind and visually impaired persons. The
      objective of this study is to determine if accessibility status changed in the
      ensuing 4 years. METHODS: Five IPs on the market in 2008 were acquired and
      analyzed for key accessibility traits such as speech and other audio output,
      tactual nature of control buttons, and the quality of visual displays. It was
      also determined whether or not a blind or visually impaired person could
      independently complete tasks such as programming the IP for insulin delivery,
      replacing batteries, and reading manuals and other documentation. RESULTS: It was
      found that IPs have not improved in accessibility since 2004. None have speech
      output, and with the exception of the Animas IR 2020, no significantly improved
      visual display characteristics were found. Documentation is still not completely
      accessible. CONCLUSION: Insulin pumps are relatively complex devices, with
      serious health consequences resulting from improper use. For IPs to be used
      safely and independently by blind and visually impaired patients, they must
      include voice output to communicate all the information presented on their
      display screens. Enhancing display contrast and the size of the displayed
      information would also improve accessibility for visually impaired users. The IPs
      must also come with accessible user documentation in alternate formats.

PMID- 20144302
TI  - Closing the circle of care with new firmware for diabetes: MyDiaBase+RxChecker.
AB  - BACKGROUND: Satisfactory glycemic control, meeting American Diabetes Association
      recommendations, is difficult to achieve. Technologically, this is most likely
      because the circle of care is incomplete. Many have suggested that the
      introduction of information technology may remedy the situation. However,
      previous attempts have not succeeded. Recognizing this, we evolved firmware that
      supports and links both the patient at home and their care providers in the
      clinic. FIRMWARE DESIGN AND METHODS: The device includes software and a database,
      all contained in a standard USB flash drive. At home, patients use the database
      portion of the device (MyDiaBase). It fully complements their diabetes education
      while capturing pertinent self-management information by tracking self-monitored
      blood glucose data, body weight, medication dosing, physical activity, diet,
      lifestyle, and stress. In the clinic, providers use the RxChecker program to
      perform prescription checks that are based on their patients' outcomes data,
      thereby effectively closing the circle of care.

PMID- 20144303
TI  - Using telemedicine to improve outcomes in diabetes--an emerging technology.

PMID- 20144304
TI  - The clinical use of hemoglobin A1c.
AB  - Hemoglobin A1c (HbA1c) has been accepted as an index of glycemic control since
      the mid-1970s and is the best marker for diabetic microvascular complications.
      Clinically, it is now used to assess glycemic control in people with diabetes.
      Assays are most reliable when certified by the National Hemoglobin
      Standardization Program but are subject to confounders and effect modifiers,
      particularly in the setting of hematologic abnormalities. Other measures of
      chronic glycemic control-fructosamine and 1,5-anhydroglucitol-are far less widely
      used. The relationship of HbA1c to average blood glucose was intensively studied
      recently, and it has been proposed that this conversion can be used to report an
      "estimated average glucose, eAG" in milligrams/deciliter or millimolar units
      rather than as per cent glycated hemoglobin. Finally, HbA1c has been proposed as
      a useful method of screening for and diagnosing diabetes.

PMID- 20144305
TI  - Biologic variability in plasma glucose, hemoglobin A1c, and advanced glycation
      end products associated with diabetes complications.
AB  - Plasma glucose plays a key role in the complications of diabetes mellitus.
      Hemoglobin A1c (HbA1c) and circulating concentrations of advanced glycation end
      products (AGEs) are central to diabetes clinical care and pathophysiology.
      However, there is evidence for variation between individuals in the relationship
      of plasma glucose to both these measures and to specific complications. The
      glycation gap (GG) and hemoglobin glycation index represent tools for
      quantitating the variability in the relationship between plasma glucose and HbA1c
      useful for identification of underlying mechanisms. Recent evidence demonstrates
      the heritability of HbA1c, the GG, and AGEs, yet not of glycated serum proteins.
      There has been tremendous effort devoted to identifying the heritable basis of
      types 1 and 2 diabetes; however, studies on the heritable contributors to these
      mediators of glucose effect on complications are only beginning. New evidence for
      normal biologic variation in the distribution of glucose into the red blood cell
      (RBC) intracellular compartment and RBC lifespan in people with and without
      diabetes represent candidates for heritable mechanisms and contributors to the
      rise in HbA1c with age. Taken as a whole, genetic and mechanistic evidence
      suggests new potential targets for complications prevention and improvement in
      complications risk estimation. These observations could help tilt the risk
      benefit balance in glycemic control toward a more beneficial outcome.

PMID- 20144306
TI  - Influence of variables on hemoglobin A1c values and nonheterogeneity of
      hemoglobin A1c reference ranges.
AB  - INTRODUCTION: Hemoglobin A1c (HbA1c) values are influenced by analytical
      interferences such as HbF and hemoglobin variants and clinical factors such as
      increased red cell turnover. Although less well-known, demographic factors such
      as race, age, and sex also influence HbA1c values. The HbA1c reference range
      should be homogenous in the United States based on the use of National
      Glycohemoglobin Standardization Program certified methods and the recommendations
      in the National Academy of Clinical Biochemistry guidelines. METHODS: Data on
      age, race, sex, HbA1c, and glucose values were extracted from the National Health
      and Nutrition Examination study for a 3 year period. A search for reference range
      data for laboratories in the United States was performed using the Google search
      engine. RESULTS: Extracted data agree with published data on the influence of
      age, sex, and smoking status on HbA1c values. There is substantial heterogeneity
      in HbA1c reference ranges in laboratories in the United States. CONCLUSION: Age,
      sex, and smoking status influence HbA1c values. Despite standardization of HbA1c
      methods and published recommendations, there is wide heterogeneity in HbA1c
      reference ranges in the United States.

PMID- 20144307
TI  - Arguments for and against the role of glucose variability in the development of
      diabetes complications.
AB  - There is now unequivocal evidence that improving glycemic control in both type 1
      and type 2 diabetes reduces the likelihood of developing the micro- and
      macrovascular complications of the disease. However, it is still unclear whether
      a patient with very variable glucose is at any different a risk of these problems
      than someone who has the same mean glucose but much more stable glycemia. This
      article reviews the evidence that exists to both support and refute the claim
      that increased glucose variability should be regarded as an independent risk
      factor for the development of diabetic vascular disease.

PMID- 20144308
TI  - Do race and ethnicity impact hemoglobin A1c independent of glycemia?
AB  - Hemoglobin A1c (HbA1c) is widely used as an index of mean glycemia, a measure of
      risk for the development of diabetes complications, and a measure of the quality
      of diabetes care. Emerging literature suggests that, although HbA1c levels change
      little over time within persons without diabetes, they vary considerably among
      individuals, suggesting that factors other than glycemia may impact HbA1c. Racial
      and ethnic differences in HbA1c have been described that do not appear to be
      explained by differences in glycemia. It is imperative that the nonglycemic
      factors that affect HbA1c be more clearly defined. Even more important, it must
      be determined whether differences among individuals or groups correlate with
      susceptibility to complications or merely reflect variation in hemoglobin
      glycation.

PMID- 20144309
TI  - Increases in whole blood glucose measurements using optically based self
      monitoring of blood glucose analyzers due to extreme Canadian winters.
AB  - BACKGROUND: Temperature and humidity have been reported to influence the results
      of whole blood glucose (WBG) measurements. METHODS: To determine whether patient
      WBG values were affected by seasonal variation, we conducted a retrospective
      analysis of 3 years' worth of weekly averages of patient WBG in five Edmonton
      hospitals. RESULTS: In all five hospitals, the winter WBG averages were
      consistently higher than the summer WBG averages, with the differences varying
      between 5% and 9%. Whole blood glucose averages were negatively correlated with
      the outside temperature. This seasonal variation was not observed in weekly
      patient averages of specimens run in a central hospital laboratory.
      INTERPRETATION: It is probable that the seasonal variation of WBG arises from the
      very low indoor humidities that are associated with external subzero
      temperatures. These increases in WBG in cold weather may be due to limitations in
      the WBG measuring systems when operated in decreased humidities and/or increased
      evaporation of the blood sample during the blood glucose measurement process. The
      implications of this seasonal variation are significant in that it (1) introduces
      increased variability in patient WBG, (2) may result in increased glucose
      lowering therapy during periods of external cold and low indoor humidity, and (3)
      confounds evaluations of WBG meter technology in geographic regions of subzero
      temperature and low indoor humidity. To mitigate the risk of diagnosing and
      treating factitious hyperglycemia, the humidity of patient care areas must be
      strictly controlled.

PMID- 20144310
TI  - Seasonal variation in hemoglobin A1c: is it the same in both hemispheres?
AB  - INTRODUCTION: There are several reports from locations in the northern hemisphere
      of seasonal variation in hemoglobin A1c (HbA1c) levels with higher values noted
      in the cooler months. The variation has been attributed to holiday seasons,
      temperature differences, and changes in diet. This article describes the seasonal
      variation in both hemispheres and in a country on the equator with minimal
      temperature variation. METHODS: The mean and median HbA1c by month was calculated
      for a maximum of 2 years for HbA1c data from the different locations: Edmonton
      and Calgary, Canada; Singapore; Melbourne, Australia; and Marshfield, Wisconsin.
      The mean monthly temperature for each location was found from available
      meteorological information. RESULTS: In both northern and southern hemispheres,
      the HbA1c was higher in cooler months and lower in the warmer months. In
      Singapore, where there is minimal temperature variation, there is also minimal
      variation in HbA1c values over the year. The difference in HbA1c over a year
      appears to be related to the difference in temperature. CONCLUSION: Hemoglobin
      A1c is higher in cooler months and lower in the warmer months in both
      hemispheres. In a country with minimal monthly temperature variation, there is
      only minimal variation in HbA1c values through the year. In all locations, the
      mean and median HbA1c declined over the study period, possibly due to better
      glycemic control of patients with diabetes or an increase in use of HbA1c as a
      screening test for diabetes or a combination of both.

PMID- 20144311
TI  - Usefulness of point-of-care testing in the treatment of diabetes in an
      underserved population.
AB  - BACKGROUND: The purpose of this article was to communicate our experience with
      point-of-care testing (POCT) using Bayer's A1CNow+ device to test glycated
      hemoglobin (A1C) in the management of diabetes and to share the observations of
      our quality control efforts. METHODS: Forty-seven patients' POCT samples were
      compared with laboratory samples to determine the validity of the POCT sample
      being drawn. Data collected represent a 10-month time period that were drawn on
      site with the following distribution: 36 samples were drawn the same day, 7
      samples were drawn 1 day later, 3 samples were drawn within 3 days, and 1 sample
      was drawn 4 days later. Although all samples were collected on-site, some of the
      samples were sent to other local branches of nationally recognized laboratories
      for analysis. RESULTS: The range of A1C results for the POCT group was 5.6 to
      >13%. The range of A1C results for the laboratory-drawn group was 5 to 12.6%.
      Twenty-four patients had laboratory results that read lower than the result
      obtained in the clinic, with an A1C range of 5 to 12.6%, and two patients had
      laboratory results that read exactly the same as the result obtained in the
      clinic when using POCT. These two individuals had A1C results of 9.1 and 12.6%.
      Analysis of data collected determined an r value of 0.918 demonstrating agreement
      between the POCT samples and the laboratory samples. CONCLUSIONS: POCT with the
      A1CNow+ is an effective, economical tool for use in a pharmacist-based diabetes
      clinic that serves a high-risk underserved population. POCT allows the pharmacist
      the ability to use on-site results to inform patients of their progress, modify
      their therapy immediately with an immediate face-to-face opportunity to assure
      understanding, and provide a self-management goal.

PMID- 20144312
TI  - The personalized medicine for diabetes meeting summary report.
AB  - Personalized medicine for diabetes is a potential method to specifically identify
      people who are at high risk of developing type 2 diabetes based on a combination
      of personal history, family history, physical examination, circulating
      biomarkers, and genome. High-risk individuals can then be referred to lifestyle
      programs for risk reduction and disease prevention. Using a personalized medicine
      approach, a patient with already-diagnosed type 2 diabetes can be treated
      individually based on information specific to that individual. The field of
      personalized medicine for diabetes is rapidly exploding. Diabetes Technology
      Society convened the Personalized Medicine for Diabetes (PMFD) Meeting March 19
      20, 2009 in San Francisco. The meeting was funded through a contract from the US
      Air Force. Diabetes experts from the military, government, academic, and industry
      communities participated. The purpose was to reach a consensus about PMFD in type
      2 diabetes to (a) establish screening programs, (b) diagnose cases at an early
      stage, and (c) monitor and treat the disease with specific measures. The group
      defined what a PMFD program should encompass, what the benefits and drawbacks of
      such a PMFD program would be, and how to overcome barriers. The group reached six
      conclusions related to the power of PMFD to improve care of type 2 diabetes by
      resulting in (1) better prediction, (2) better prophylactic interventions, (3)
      better treatments, and (4) decreased cardiovascular disease burden. Additional
      research is needed to demonstrate the benefits of this approach. The US Air Force
      is well positioned to conduct research and develop clinical programs in PMFD.

PMID- 20144313
TI  - The case for personalized medicine.
AB  - Personalized medicine may be considered an extension of traditional approaches to
      understanding and treating disease, but with greater precision. Physicians may
      now use a patient's genetic variation or expression profile as well as protein
      and metabolic markers to guide the selection of certain drugs or treatments. In
      many cases, the information provided by molecular markers predicts susceptibility
      to conditions. The added precision introduces the possibility of a more
      preventive, effective approach to clinical care and reductions in the duration
      and cost of clinical trials. Here, we make the case, through real-world examples,
      that personalized medicine is delivering significant value to individuals, to
      industry, and to the health care system overall and that it will continue to grow
      in importance if we can lift the barriers that impede its adoption and build
      incentives to encourage its practice.

PMID- 20144314
TI  - Genetics factors contributing to type 2 diabetes across ethnicities.
AB  - Type 2 diabetes mellitus (T2DM) is among the many common diseases with a strong
      genetic component, but until recently, the variants causing this disease remained
      largely undiscovered. With the ability to interrogate most of the variation in
      the genome, the number of genetic variants has grown from 2 to 19 genes, many
      with multiple variants. An additional three genes are associated primarily with
      fasting glucose rather than T2DM. Despite the plethora of new markers, the
      individual effect is uniformly small, and the cumulative effect explains little
      of the genetic risk for T2DM. Furthermore, the success is largely restricted to
      European populations. Despite success in mapping genes in Asian populations,
      success in United States minorities, particularly African Americans, has been
      limited. The genetic findings highlight the role of the beta cell in diabetes
      pathogenesis, but much remains to be discovered before genetic prediction and
      individualized medicine can become a reality for this disease.

PMID- 20144315
TI  - Genetic susceptibility to type 2 diabetes and implications for therapy.
AB  - Since 2000, we have witnessed an explosion of known genetic determinants of type
      2 diabetes risk. These findings have seeded the expectation that our ability to
      make personalized, predictive, therapeutic clinical decisions is imminent.
      However, the loci discovered to date explain only a small fraction of overall
      inheritable risk for this disease. In many cases, the reported associations
      merely signal regions of the genome that are overrepresented in disease versus
      health but do not identify the causal variants. Well-powered cohort studies have
      shown that the set of markers detected thus far does not significantly improve
      individual risk prediction or stratification over common clinical variables, with
      the possible exception of younger subjects. On the other hand, risk genotypes may
      help target subgroups for more intensive surveillance or prevention efforts,
      although whether such a strategy improves patient outcomes and/or is cost
      effective should be examined. Similarly, whether genetic information will help
      guide therapeutic decisions must be tested in adequately designed and rigorously
      conducted clinical trials.

PMID- 20144316
TI  - Effects of glycemic load on metabolic health and type 2 diabetes mellitus.
AB  - A large body of epidemiologic evidence has demonstrated that the combination of a
      Western diet and lifestyle is primarily responsible for the increased metabolic
      disease risk, such as obesity, type 2 diabetes mellitus (T2DM), and metabolic
      syndrome, noted in society today. Thus finding optimal intervention strategies to
      combat these growing epidemics is imperative. Despite some controversy, a growing
      body of literature indicates that one aspect of diet that likely affects
      phenotypic outcomes and metabolic disease risk is the glycemic load (GL). This
      brief review will provide an overview of the GL concept, discuss epidemiologic
      work investigating relationships between both GL and metabolic risk factors, as
      well as intervention studies that have assessed the impact of GL on phenotypic
      outcomes related to T2DM and cardiovascular disease. Overall, a low dietary GL
      may be protective against metabolic disease and should be considered as a
      healthful dietary component.

PMID- 20144317
TI  - Pharmacogenetics for type 2 diabetes: practical considerations for study design.
AB  - There is a relative dearth of studies designed to elucidate genetic variation
      that can explain differences in the response to diabetes pharmacotherapy. When
      designing such studies, appropriate consideration of the various nongenetic
      variables that can affect the treatment response is necessary. In addition,
      disease stage and prior pharmacotherapy also influence drug efficacy. Selecting
      the appropriate genetic variant to test in such studies is also important, and
      common variants (known to be functional or otherwise) in a given candidate locus
      should be tested for the effect on the treatment response. Finally, an
      appropriate measure of treatment response is necessary to enable detection of
      pharmacogenetic effects. Perhaps prior to undertaking such studies, smaller
      studies utilizing well-characterized, homogenous populations with normal glucose
      tolerance or prediabetes (to avoid the problem of disease effects on treatment
      response) and surrogate measures of response such as insulin secretion should be
      completed.

PMID- 20144318
TI  - A strategy for analyzing gene-nutrient interactions in type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM), like all chronic diseases, results from
      interactions between multiple genes and multiple environmental factors.
      Nevertheless, many research studies focus on either nutrition or genetic factors
      independently of each other. The challenges of analyzing gene-nutrient
      interactions in T2DM are the (i) genetic heterogeneity in humans, (ii) complexity
      of environmental factors, particularly dietary chemicals, and (iii) diverse
      physiologies that produce the same apparent disease. Many of these variables are
      not accounted for in the design or study of T2DM or, indeed, most chronic
      diseases, although exceptions are noteworthy. Establishing experimental paradigms
      to analyze the complexity of these interactions and physiologies is challenging,
      but possible. This article provides a strategy to extend nutrigenomic
      experimental strategies to include early environmental influences that may
      promote adult-onset disease.

PMID- 20144319
TI  - Detecting undiagnosed type 2 diabetes: family history as a risk factor and
      screening tool.
AB  - A family history of diabetes is a major risk factor for the disease. As such, it
      is often included in a variety of tools designed to detect either people at risk
      of diabetes or people with undiagnosed diabetes. One of the reasons to screen for
      diabetes is that it has a prolonged asymptomatic phase, which includes impaired
      fasting glucose, impaired glucose tolerance, and the early stages of diabetes. In
      terms of prevalence, diabetes is a major public health problem. Evidence shows
      that the detection of impaired glucose metabolism in its early stages
      (prediabetes) could lead to the delay or prevention of the disease and its
      complications. However, the issue of using family history to screen for diabetes
      must be discussed within the context of screening for diabetes in general.
      Screening for a disease among asymptomatic people must meet a series of stringent
      requirements to ensure the best possible outcomes. Screening for diabetes meets
      most of these requirements but the ones it does not meet are still important.
      Therefore, based on systematically collected evidence or simply by consensus
      among scientists, influential organizations recommend screening only among high
      risk individuals. As a result, researchers have developed a variety of simple
      tools to identify high-risk individuals for diabetes in populations. Family
      history is included as a key variable in the vast majority of them. This article
      is a brief overview of the reasons to screen for diabetes in general, the tools
      available for conducting this screening, and the role of family history in these
      tools.

PMID- 20144320
TI  - Environmental influences on development of type 2 diabetes and obesity:
      challenges in personalizing prevention and management.
AB  - Recent epidemic increases in the U.S. prevalence of obesity and diabetes are a
      consequence of widespread environmental changes affecting energy balance and its
      regulation. These environmental changes range from exposure to endocrine
      disrupting pollutants to shortened sleep duration to physical inactivity to
      excess caloric intake. Overall, we need a better understanding of the factors
      affecting individual susceptibility and resistance to adverse exposures and
      behaviors and of determinants of individual response to treatment. Obesity and
      diabetes prevention will require responding to two primary behavioral risk
      factors: excess energy intake and insufficient energy expenditure. Adverse food
      environments (external, nonphysiological influences on eating behaviors)
      contribute to excess caloric intake but can be countered through behavioral and
      economic approaches. Adverse built environments, which can be modified to foster
      more physical activity, are promising venues for community-level intervention.
      Techniques to help people to modulate energy intake and increase energy
      expenditure must address their personal situations: health literacy,
      psychological factors, and social relationships. Behaviorally oriented
      translational research can help in developing useful interventions and
      environmental modifications that are tailored to individual needs.

PMID- 20144321
TI  - Technologies for diabetes genomics.
AB  - The genetic risk for diabetes largely depends on the type of diabetes and the
      penetrance and severity of the effect of the contributing genes. This ranges from
      the high-risk mutations of neonatal diabetes and maturityonset diabetes of the
      young to the lower, but still significant, risk conferred by common human
      leukocyte antigen alleles in type 1 diabetes to the still-lower risk conferred by
      the common variants associated with type 2 diabetes. There are many new molecular
      technologies, each with their own set of methodological issues, that have been
      used for genome-wide association studies and that can be used for determining the
      genetic risk for these various types of diabetes. These technologies include
      whole genome single nucleotide polymorphism microarrays, high-throughput
      polymorphism analyzers, next-generation sequencers, and copy-number variant
      technologies.

PMID- 20144322
TI  - Personalized medicine in diabetes: regulatory considerations.
AB  - Personalized medicine has become a topic of great interest because of its
      potential to improve patient care and optimize therapeutic strategy. The U.S.
      Food and Drug Administration (FDA) is interested in promoting personalized
      medicine, whenever appropriate, to protect and promote the public health. The
      ability to better diagnose, screen, and manage patients with diabetes in order to
      individualize care should lead to better health outcomes and a large benefit to
      public health. This article describes FDA regulatory considerations for devices
      intended for use as personalized medicine tools for the diagnosis and treatment
      of patients with diabetes.

PMID- 20144323
TI  - Circulating biomarkers of glycemia in diabetes management and implications for
      personalized medicine.
AB  - Personalized medicine represents a new model in how the medical community
      approaches disease management. Rather than managing those with a particular
      diagnosis according to an established guideline, the personalized medicine model
      seeks to identify unique characteristics within each patient that can serve as a
      basis for disease characterization and specialized treatment. This article
      reviews several circulating biomarkers of glycemia that are used in the medical
      management of diabetes, to include hemoglobin A1c, fructosamine, and 1,5
      anhydroglucitol. Within the discussion, specific attention is paid to areas in
      which biomarker results do not correlate with anticipated results based on actual
      mean glycemia. Variability between actual and anticipated results of the various
      biomarker tests represents opportunities to identify previously undefined
      subcategories of diabetes and groups of patients that fit into these
      subcategories. Finally, research areas are proposed for these subcategories that
      would further promote the field of personalized medicine in diabetes.

PMID- 20144324
TI  - Validation of a multimarker model for assessing risk of type 2 diabetes from a
      five-year prospective study of 6784 Danish people (Inter99).
AB  - BACKGROUND: Improved identification of subjects at high risk for development of
      type 2 diabetes would allow preventive interventions to be targeted toward
      individuals most likely to benefit. In previous research, predictive biomarkers
      were identified and used to develop multivariate models to assess an individual's
      risk of developing diabetes. Here we describe the training and validation of the
      PreDx Diabetes Risk Score (DRS) model in a clinical laboratory setting using
      baseline serum samples from subjects in the Inter99 cohort, a population-based
      primary prevention study of cardiovascular disease. METHODS: Among 6784 subjects
      free of diabetes at baseline, 215 subjects progressed to diabetes (converters)
      during five years of follow-up. A nested case-control study was performed using
      serum samples from 202 converters and 597 randomly selected nonconverters.
      Samples were randomly assigned to equally sized training and validation sets.
      Seven biomarkers were measured using assays developed for use in a clinical
      reference laboratory. RESULTS: The PreDx DRS model performed better on the
      training set (area under the curve [AUC] = 0.837) than fasting plasma glucose
      alone (AUC = 0.779). When applied to the sequestered validation set, the PreDx
      DRS showed the same performance (AUC = 0.838), thus validating the model. This
      model had a better AUC than any other single measure from a fasting sample.
      Moreover, the model provided further risk stratification among high-risk
      subpopulations with impaired fasting glucose or metabolic syndrome. CONCLUSIONS:
      The PreDx DRS provides the absolute risk of diabetes conversion in five years for
      subjects identified to be "at risk" using the clinical factors.

PMID- 20144325
TI  - The prevention of type 2 diabetes: an overview.
AB  - Type 2 diabetes mellitus is one of the major public health threats in the United
      States today, reaching epidemic rates. Epidemiological evidence suggests a strong
      link between obesity and the risk of developing diabetes. Increasing evidence
      demonstrates that lifestyle interventions can significantly delay or possibly
      prevent the onset of type 2 diabetes in persons with increased risk. Despite
      these findings, there remain important barriers to the translation of this
      research to the public health. These include identifying persons with an
      increased risk for developing the disease and the lack of easily accessible, cost
      effective intervention programs. At least one study, however, has effectively
      implemented an evidenced-based intervention in community settings, suggesting
      that it may be possible to develop a model for the national scalability of
      primary prevention in the United States.

PMID- 20144326
TI  - Waist circumference threshold values for type 2 diabetes risk.
AB  - Adult gains in body weight, excess adiposity, and intra-abdominal fat have each
      been associated with risk for type 2 diabetes mellitus (T2DM), forming the basis
      for preventive medicine guidelines and actuarial predictions using practical
      indices of weight (e.g., body mass index [BMI]) and waist circumference (WC). As
      obesity-related disease spreads beyond affluent western countries, application of
      WC thresholds to other populations has highlighted issues of their
      generalizability. For example, U.S. national health goals based on BMI < 25
      kg/m(2) and WC < 89 cm (women) and <102 cm (men) differ considerably with a
      recent law in Japan mandating intervention for older adults with WC exceeding 90
      cm (women) and 85 cm (men). The U.S. military has also faced issues of
      generalizability of WC-based adiposity standards that are fair and achievable.
      Data from many studies indicate that WC is a reliable biomarker for T2DM risk,
      suggesting that, for adult men and women, action thresholds should be more
      stringent than current U.S. guidelines, and it would not be harmful to set
      worldwide targets somewhere below 90 cm for men and women, regardless of weight
      status. Medical technology has provided many great insights into disease,
      including modern imaging technologies that have differentiated fat depots that
      have the greatest influence on T2DM, but ultimately, an inexpensive measuring
      tape provides the most useful and cost-effective preventive measure for T2DM
      today. At some point in the future, a Star Trek-like abdominal body fat
      "tricorder" noninvasive assessment of tissue composition may provide an advantage
      over abdominal girth.

PMID- 20144327
TI  - A genomics study of type 2 diabetes mellitus in U.S. Air Force personnel.
AB  - The military community is at high risk for type 2 diabetes (T2D), especially as
      it relates to military beneficiaries, although preventive measures can be
      implemented to reduce disease onset. This study evaluates the prevalence of risk
      associated single nucleotide polymorphisms in patients diagnosed with T2D within
      active duty, retired military, and military-dependent populations on Lackland Air
      Force Base compared to nondiabetic controls. Results will be used as a basis of
      comparison to analyze risk-conferring genotypes in the young, healthy active duty
      population to generate the prevalence of T2D risk-associated factors in our
      current and future war fighters. Identifying genetic markers of T2D prior to
      abnormal glucose control and insulin resistance may ultimately adjust future risk
      through early detection, healthy lifestyle modifications, and disease management
      programs.

PMID- 20144328
TI  - Noninvasive optical screening for diabetes.
AB  - BACKGROUND: Advanced glycation end products (AGEs) are implicated in the
      complications of diabetes. Advanced glycation end products also accumulate in the
      skin and are sensitive biomarkers for the risk of developing diabetes and related
      complications. Some AGEs fluoresce and can be measured noninvasively by optical
      spectroscopy. METHODS: Noninvasive screening for diabetes has been evaluated in
      an 18-site study involving a cohort of 2793 subjects meeting American Diabetes
      Association-based screening criteria. Subjects were measured with a specialized
      skin fluorimeter and also received traditional blood glucose and glycated
      hemoglobin tests. RESULTS: Retrospective results indicated that the noninvasive
      technology measuring dermal fluorescence is more sensitive at detecting abnormal
      glucose tolerance than either fasting plasma glucose or glycated hemoglobin A1C.
      CONCLUSIONS: These results suggest that noninvasive measurement of dermal
      fluorescence may be an effective tool to identify individuals at risk for
      diabetes and its complications. The noninvasive technology yields immediate
      results, and since measuring dermal fluorescence requires no blood draws or
      patient fasting, the instrument may be well suited for opportunistic screening.

PMID- 20144329
TI  - Ethical issues of predictive genetic testing for diabetes.
AB  - With the rising number of individuals affected with diabetes and the significant
      health care costs of treatment, the emphasis on prevention is key to controlling
      the health burden of this disease. Several genetic and genomic studies have
      identified genetic variants associated with increased risk to diabetes. As a
      result, commercial testing is available to predict an individual's genetic risk.
      Although the clinical benefits of testing have not yet been demonstrated, it is
      worth considering some of the ethical implications of testing for this common
      chronic disease. In this article, I discuss several issues that should be
      considered during the translation of predictive testing for diabetes, including
      familial implications, improvement of risk communication, implications for
      behavioral change and health outcomes, the Genetic Information Nondiscrimination
      Act, direct-to-consumer testing, and appropriate age of testing.

PMID- 20144330
TI  - A feasibility study of bihormonal closed-loop blood glucose control using dual
      subcutaneous infusion of insulin and glucagon in ambulatory diabetic swine.
AB  - BACKGROUND: We sought to test the feasibility and efficacy of bihormonal closed
      loop blood glucose (BG) control that utilizes subcutaneous (SC) infusion of
      insulin and glucagon, a model-predictive control algorithm for determining
      insulin dosing, and a proportional-derivative control algorithm for determining
      glucagon dosing. METHODS: Thirteen closed-loop experiments (approximately 7-27 h
      in length) were conducted in six ambulatory diabetic pigs weighing 26-50 kg. In
      all experiments, venous BG was sampled through a central line in the vena cava.
      Efficacy was evaluated in terms of the controller's ability to regulate BG in
      response to large meal disturbances ( approximately 5 g of carbohydrate per
      kilogram of body mass per meal) based only on regular frequent venous BG sampling
      and requiring only the subject's weight for initialization. RESULTS: Closed-loop
      results demonstrated successful BG regulation to normoglycemic range, with
      average insulin-to-carbohydrate ratios between approximately 1:20 and 1:40 U/g.
      The total insulin bolus doses averaged approximately 6 U for a meal containing
      approximately 6 g per kilogram body mass. Mean BG values in two 24 h experiments
      were approximately 142 and approximately 155 mg/dl, with the total daily dose
      (TDD) of insulin being approximately 0.8-1.0 U per kilogram of body mass and the
      TDD of glucagon being approximately 0.02-0.05 mg. Results also affirmed the
      efficacy of SC doses of glucagon in staving off episodic hypoglycemia.
      CONCLUSIONS: We demonstrate the feasibility of bihormonal closed-loop BG
      regulation using a control system that employs SC infusion of insulin and
      glucagon as governed by an algorithm that reacts only to BG without any feed
      forward information regarding carbohydrate consumption or physical activity. As
      such, this study can reasonably be regarded as the first practical implementation
      of an artificial endocrine pancreas that has a hormonally derived
      counterregulatory capability.

PMID- 20144331
TI  - Improved glycemic control through continuous glucose sensor-augmented insulin
      pump therapy: prospective results from a community and academic practice patient
      registry.
AB  - BACKGROUND: Conducted by highly experienced investigators with abundant time and
      resources, phase III studies of continuous glucose sensing (CGS) may lack
      generalizability to everyday clinical practice. METHOD: Community or academic
      practices in six Central and Eastern European or Mediterranean countries
      prospectively established an anonymized registry of consecutive patients with
      type 1 insulin-dependent diabetes mellitus starting CGS-augmented insulin pump
      therapy with the Paradigm X22 (Medtronic MiniMed, Northridge, CA) under everyday
      conditions, without prior CGS with another device. We compared glycosylated
      hemoglobin (GHb) values before and after 3 months of CGS and assessed
      relationships between insulin therapy variables and glycemia-related variables at
      weeks 1, 4, and 12 of CGS. RESULTS: Of 102 enrolled patients, 85 (83%) with
      complete weeks 1, 4, and 12 sensor data and baseline/3-month GHb data were
      evaluable. Evaluable patients were approximately 54% male and approximately 75%
      adult (mean age, 33.2 +/- 16.9 years) with longstanding diabetes and high
      personal/family education levels. Mean GHb declined significantly after 3 months
      of CGS (7.55 +/- 1.33% at baseline to 6.81 +/- 1.08% after 12 weeks, 0.74%
      absolute decrease, P < 0.001). The absolute GHb reduction correlated
      significantly (P < 0.0005) with baseline GHb: larger absolute reductions tended
      to occur when baseline levels were higher. An increased basal insulin dose as a
      percentage of the total daily insulin dose and a decreased daily bolus count from
      week 1 to week 12 of CGS predicted GHb improvement from baseline to week 12.
      CONCLUSIONS: CGS-augmented insulin pump therapy appears to improve glycemic
      control in type 1 diabetes in varied everyday practice settings.

PMID- 20144332
TI  - Six-year retrospective follow-up study of safe screening intervals for sight
      threatening retinopathy in patients with diabetes mellitus.
AB  - BACKGROUND: We estimate safe screening intervals for sight-threatening diabetic
      retinopathy (STDR). METHODS: A 6-year retrospective follow-up study to review
      screening results of two cohorts of patients with diabetes mellitus (DM) was
      conducted; a cohort free of diabetic retinopathy (DR) and a cohort with mild
      nonproliferative diabetic retinopathy (NPDR) at baseline. Patients had been
      screened by means of a nonmydriatic retinal camera. Baseline age, sex, and
      diabetes characteristics were also collected. Statistical analysis was based on
      life-table method of risk estimation. RESULTS: A total of 286 patients with DM
      free of DR and 144 patients with mild NPDR at baseline were included in the
      study. For patients free of DR, the probability of remaining free of STDR was 97%
      (95% confidence interval [CI] 94-99%) at the end of the fourth year. In this
      cohort of patients, those with type 2 DM were more likely to progress to STDR
      than those who had type 1 DM (p < .01). For patients with mild NPDR, the
      probability of remaining free of STDR dropped to 94% (95% CI 88-97%) at the end
      of the second year, and it was still 100% at the end of the second year for those
      with a glycated hemoglobin level < or =7.5% at baseline (p < .05). CONCLUSIONS:
      Screening at a 3-4 year interval for diabetes patients free of DR is safe because
      of their low risk of developing STDR. Patients with mild NPDR require screening
      at a 1 year interval, or at a 2 year interval with good metabolic control.

PMID- 20144333
TI  - Screening for diabetic retinopathy using computer vision and physiological
      markers.
AB  - BACKGROUND: Hyperglycemia and diabetes result in vascular complications, most
      notably diabetic retinopathy (DR). The prevalence of DR is growing and is a
      leading cause of blindness and/or visual impairment in developed countries.
      Current methods of detecting, screening, and monitoring DR are based on
      subjective human evaluation, which is also slow and time-consuming. As a result,
      initiation and progress monitoring of DR is clinically hard. METHODS: Computer
      vision methods are developed to isolate and detect two of the most common DR
      dysfunctions-dot hemorrhages (DH) and exudates. The algorithms use specific color
      channels and segmentation methods to separate these DR manifestations from
      physiological features in digital fundus images. The algorithms are tested on the
      first 100 images from a published database. The diagnostic outcome and the
      resulting positive and negative prediction values (PPV and NPV) are reported. The
      first 50 images are marked with specialist determined ground truth for each
      individual exudate and/or DH, which are also compared to algorithm
      identification. RESULTS: Exudate identification had 96.7% sensitivity and 94.9%
      specificity for diagnosis (PPV = 97%, NPV = 95%). Dot hemorrhage identification
      had 98.7% sensitivity and 100% specificity (PPV = 100%, NPV = 96%). Greater than
      95% of ground truth identified exudates, and DHs were found by the algorithm in
      the marked first 50 images, with less than 0.5% false positives. CONCLUSIONS: A
      direct computer vision approach enabled high-quality identification of exudates
      and DHs in an independent data set of fundus images. The methods are readily
      generalizable to other clinical manifestations of DR. The results justify a
      blinded clinical trial of the system to prove its capability to detect, diagnose,
      and, over the long term, monitor the state of DR in individuals with diabetes.

PMID- 20144335
TI  - An evaluation of "I, Pancreas" algorithm performance in silico.
AB  - BACKGROUND: The objective of this study was to investigate the performance of a
      newly proposed insulin titrating algorithm to achieve tight glycemic control in
      the critically ill. METHODS: A simulation environment with 10 critically ill
      virtual subjects was employed to evaluate the "I, Pancreas" algorithm proposed by
      Braithwaite et al. and described in an article in this issue of Journal of
      Diabetes Science and Technology. The algorithm was coded in MATLAB and was
      "plugged in" to a simulation environment to provide glucose control in a 48-hour
      long simulated study. RESULTS: Mean blood glucose was 6.5 +/- 0.4 mmol/liter (118
      +/- 7.8 mg/dl), percentage of time spent in the target glucose range was 38% (32
      44%), and the hyperglycemic index was 0.6 (0.4 -1.0) mmol/liter [11.1 (7.7-18.1)
      mg/dl]. A single episode of mild hypoglycemia at 3.8 mmol/liter (69 mg/dl) was
      observed during 480 hours of glucose control. CONCLUSION: In this initial in
      silico evaluation, the "I, Pancreas" algorithm provided a safe control of glucose
      in the simulated study and achieved tight glycemic control 38% of the time.

PMID- 20144334
TI  - Intermediary variables and algorithm parameters for an electronic algorithm for
      intravenous insulin infusion.
AB  - BACKGROUND: Algorithms for intravenous insulin infusion may assign the infusion
      rate (IR) by a two-step process. First, the previous insulin infusion rate
      (IR(previous)) and the rate of change of blood glucose (BG) from the previous
      iteration of the algorithm are used to estimate the maintenance rate (MR) of
      insulin infusion. Second, the insulin IR for the next iteration (IR(next)) is
      assigned to be commensurate with the MR and the distance of the current blood
      glucose (BG(current)) from target. With use of a specific set of algorithm
      parameter values, a family of iso-MR curves is created, each giving IR as a
      function of MR and BG. METHOD: To test the feasibility of estimating MR from the
      IR(previous) and the previous rate of change of BG, historical hyperglycemic data
      points were used to compute the "maintenance rate cross step next estimate"
      (MR(csne)). Historical cases had been treated with intravenous insulin infusion
      using a tabular protocol that estimated MR according to column-change rules. The
      mean IR on historical stable intervals (MR(true)), an estimate of the biologic
      value of MR, was compared to MR(csne) during the hyperglycemic iteration
      immediately preceding the stable interval. Hypothetically calculated MR(csne)
      dependent IR(next) was compared to IR(next) assigned historically. An expanded
      theory of an algorithm is developed mathematically. Practical recommendations for
      computerization are proposed. RESULTS: The MR(true) determined on each of 30
      stable intervals and the MR(csne) during the immediately preceding hyperglycemic
      iteration differed, having medians with interquartile ranges 2.7 (1.2-3.7) and
      3.2 (1.5-4.6) units/h, respectively. However, these estimates of MR were strongly
      correlated (R(2) = 0.88). During hyperglycemia at 941 time points the IR(next)
      assigned historically and the hypothetically calculated MR(csne)-dependent
      IR(next) differed, having medians with interquartile ranges 4.0 (3.0-6.0) and 4.6
      (3.0-6.8) units/h, respectively, but these paired values again were correlated
      (R(2) = 0.87). This article describes a programmable algorithm for intravenous
      insulin infusion. The fundamental equation of the algorithm gives the
      relationship among IR; the biologic parameter MR; and two variables expressing an
      instantaneous rate of change of BG, one of which must be zero at any given point
      in time and the other positive, negative, or zero, namely the rate of change of
      BG from below target (rate of ascent) and the rate of change of BG from above
      target (rate of descent). In addition to user-definable parameters, three special
      algorithm parameters discoverable in nature are described: the maximum rate of
      the spontaneous ascent of blood glucose during nonhypoglycemia, the glucose per
      daily dose of insulin exogenously mediated, and the MR at given patient time
      points. User-assignable parameters will facilitate adaptation to different
      patient populations. CONCLUSIONS: An algorithm is described that estimates MR
      prior to the attainment of euglycemia and computes MR-dependent values for
      IR(next). Design features address glycemic variability, promote safety with
      respect to hypoglycemia, and define a method for specifying glycemic targets that
      are allowed to differ according to patient condition.

PMID- 20144336
TI  - Enhanced glucose sensor linearity using poly(vinyl alcohol) hydrogels.
AB  - BACKGROUND: High linearities, sensitivities, and low oxygen dependence constitute
      prime requisites for electrochemical glucose sensors. However, for implantable
      sensors the need to control tissue inflammation requires the use outer membranes
      that permit inward analyte diffusion while continuously releasing anti
      inflammatory drugs and other tissue response-modifying (TRM) agents. We have
      shown previously that while outer membranes based on layer-by-layer (LBL)
      assembly enhance linearity, poly(vinyl alcohol)(PVA) hydrogels loaded with TRM
      containing microspheres enable a significant reduction in tissue inflammation.
      This article discusses amperometric performance of glucose sensors coated with
      stacked LBL/PVA hydrogel outer membranes. METHODS: Sensors were fabricated by
      immobilizing glucose oxidase enzyme on a 50-microm platinum wire followed by
      deposition of stacked LBL/PVA hydrogel outer membranes. The sensor response to
      various glucose concentrations was determined by applying 0.7 V vs an Ag/AgCl
      reference electrode in phosphate-buffered saline (37 degrees C). Michaelis-Menten
      analysis was performed to quantify sensor performance in terms of linearity
      (K(m,glu)(app)) and oxygen dependence (K(m,O(2))(app)/[Glucose]). RESULTS: When
      overlaid onto LBL-assembled outer membranes, PVA hydrogels improved sensor
      linearity by 60% from 10 to 16 mM of glucose and resulted in a twofold decrease
      in oxygen dependence. CONCLUSIONS: Enhancement in the performance of a PVA-coated
      sensor is attributed to the oxygen-storing capability of PVA hydrogel due to the
      formation of hydrophobic domains during its freezing and thawing employed to
      physical cross-link the PVA. Such membranes with the capability to release TRMs
      continuously while storing oxygen constitute a major improvement over current
      outer membrane technologies.

PMID- 20144337
TI  - A minimal C-peptide sampling method to capture peak and total prehepatic insulin
      secretion in model-based experimental insulin sensitivity studies.
AB  - AIMS AND BACKGROUND: Model-based insulin sensitivity testing via the intravenous
      glucose tolerance test (IVGTT) or similar is clinically very intensive due to the
      need for frequent sampling to accurately capture the dynamics of insulin
      secretion and clearance. The goal of this study was to significantly reduce the
      number of samples required in intravenous glucose tolerance test protocols to
      accurately identify C-peptide and insulin secretion characteristics. METHODS:
      Frequently sampled IVGTT data from 12 subjects [5 normal glucose-tolerant (NGT)
      and 7 type 2 diabetes mellitus (T2DM)] were analyzed to calculate insulin and C
      peptide secretion using a well-accepted C-peptide model. Samples were reduced in
      a series of steps based on the critical IVGTT profile points required for the
      accurate estimation of C-peptide secretion. The full data set of 23 measurements
      was reduced to sets with six or four measurements. The peak secretion rate and
      total secreted C-peptide during 10 and 20 minutes postglucose input and during
      the total test time were calculated. Results were compared to those from the full
      data set using the Wilcoxon rank sum to assess any differences. RESULTS: In each
      case, the calculated secretion metrics were largely unchanged, within expected
      assay variation, and not significantly different from results obtained using the
      full 23 measurement data set (P < 0.05). CONCLUSIONS: Peak and total C-peptide
      and insulin secretory characteristics can be estimated accurately in an IVGTT
      from as few as four systematically chosen samples, providing an opportunity to
      minimize sampling, cost, and burden.

PMID- 20144338
TI  - A physiological model of the effect of hypoglycemia on plasma potassium.
AB  - BACKGROUND: Adrenaline release and excess insulin during hypoglycemia stimulate
      the uptake of potassium from the bloodstream, causing low plasma potassium
      (hypokalemia). Hypokalemia has a profound effect on the heart and is associated
      with an increased risk of malignant cardiac arrhythmias. It is the aim of this
      study to develop a physiological model of potassium changes during hypoglycemia
      to better understand the effect of hypoglycemia on plasma potassium. METHOD:
      Potassium counterregulation to hypokalemia was modeled as a linear function
      dependent on the absolute potassium level. An insulin-induced uptake of potassium
      was modeled using a negative exponential function, and an adrenaline-induced
      uptake of potassium was modeled as a linear function. Functional expressions for
      the three components were found using published data. RESULTS: The performance of
      the model was evaluated by simulating plasma potassium from three published
      studies. Simulations were done using measured levels of adrenaline and insulin.
      The mean root mean squared error (RMSE) of simulating plasma potassium from the
      three studies was 0.09 mmol/liter, and the mean normalized RMSE was 14%. The mean
      difference between nadirs in simulated and measured potassium was 0.12
      mmol/liter. CONCLUSIONS: The presented model simulated plasma potassium with good
      accuracy in a wide range of clinical settings. The limited number of hypoglycemic
      episodes in the test set necessitates further tests to substantiate the ability
      of the model to simulate potassium during hypoglycemia. In conclusion, the model
      is a good first step toward better understanding of changes in plasma potassium
      during hypoglycemia.

PMID- 20144339
TI  - Computing the risk of postprandial hypo- and hyperglycemia in type 1 diabetes
      mellitus considering intrapatient variability and other sources of uncertainty.
AB  - OBJECTIVE: The objective of this article was to develop a methodology to quantify
      the risk of suffering different grades of hypo- and hyperglycemia episodes in the
      postprandial state. METHODS: Interval predictions of patient postprandial glucose
      were performed during a 5-hour period after a meal for a set of 3315 scenarios.
      Uncertainty in the patient's insulin sensitivities and carbohydrate (CHO)
      contents of the planned meal was considered. A normalized area under the curve of
      the worst-case predicted glucose excursion for severe and mild hypo- and
      hyperglycemia glucose ranges was obtained and weighted accordingly to their
      importance. As a result, a comprehensive risk measure was obtained. A reference
      model of preprandial glucose values representing the behavior in different ranges
      was chosen by a xi(2) test. The relationship between the computed risk index and
      the probability of occurrence of events was analyzed for these reference models
      through 19,500 Monte Carlo simulations. RESULTS: The obtained reference models
      for each preprandial glucose range were 100, 160, and 220 mg/dl. A relationship
      between the risk index ranges <10, 10-60, 60-120, and >120 and the probability of
      occurrence of mild and severe postprandial hyper- and hypoglycemia can be
      derived. CONCLUSIONS: When intrapatient variability and uncertainty in the CHO
      content of the meal are considered, a safer prediction of possible hyper- and
      hypoglycemia episodes induced by the tested insulin therapy can be calculated.

PMID- 20144340
TI  - Factors affecting blood glucose monitoring: sources of errors in measurement.
AB  - Glucose monitoring has become an integral part of diabetes care but has some
      limitations in accuracy. Accuracy may be limited due to strip manufacturing
      variances, strip storage, and aging. They may also be due to limitations on the
      environment such as temperature or altitude or to patient factors such as
      improper coding, incorrect hand washing, altered hematocrit, or naturally
      occurring interfering substances. Finally, exogenous interfering substances may
      contribute errors to the system evaluation of blood glucose. In this review, I
      discuss the measurement of error in blood glucose, the sources of error, and
      their mechanism and potential solutions to improve accuracy in the hands of the
      patient. I also discuss the clinical measurement of system accuracy and methods
      of judging the suitability of clinical trials and finally some methods of
      overcoming the inaccuracies. I have included comments about additional
      information or education that could be done today by manufacturers in the
      appropriate sections. Areas that require additional work are discussed in the
      final section.

PMID- 20144341
TI  - Exercise and glucose metabolism in persons with diabetes mellitus: perspectives
      on the role for continuous glucose monitoring.
AB  - Exercise causes profound changes in glucose homeostasis. For people with type 1
      diabetes, aerobic exercise usually causes blood glucose concentration to drop
      rapidly, while anaerobic exercise may cause it to rise, thereby making glycemic
      control challenging. Having the capacity to know their glucose levels and the
      direction of change during exercise increases self-efficacy in these persons who
      are prone to hypo- and hyperglycemia. For people with type 2 diabetes, learning
      first hand that regular exercise improves glucose levels may be a motivating
      factor in getting them to be more active. Continuous glucose monitoring is a
      potentially useful adjunct to diabetes management for the active person with
      either forms of diabetes. This review aims to guide the reader to use this
      technology to its maximum advantage by providing an overview of technical
      features, performance characteristics, and clinical utility, all balanced against
      the limitations that may be more prominent during physical activity.

PMID- 20144342
TI  - Antisense oligonucleotide therapy in diabetic retinopathy.
AB  - Diabetic retinopathy is one of the leading causes of blindness in the United
      States and other parts of the world. Historically, laser photocoagulation and
      vitrectomy surgery have been used for the treatment of diabetic retinopathy,
      including diabetic macular edema. Both procedures have proven to be useful under
      certain conditions but have their limitations. New pathways and processes that
      promote diabetic retinopathy have been identified, and several new therapeutic
      approaches are under investigation. These new therapies may be beneficial in the
      treatment of diabetic retinopathy and include antivascular endothelial growth
      factor agents, corticosteroids, and therapies that may potentially target a
      number of additional diabetic retinopathy-related factors and processes,
      including antisense oligonucleotides. Second-generation antisense
      oligonucleotides, such as iCo-007, may offer a significant advantage in the
      treatment of diabetic retinopathy by downregulating the signal pathways of
      multiple growth factors that seem to play a critical role in the process of
      ocular angiogenesis and vascular leakage. Benefits of such molecules are expected
      to include the specificity of the kinase target and an extended half-life,
      resulting in less frequent intravitreal drug administration, resistance to
      molecule degradation, and a good safety profile.

PMID- 20144343
TI  - The effect of reduced somatosensation on standing balance: a systematic review.
AB  - The objective of this review is to identify and review publications describing
      the impact of reduced somatosensation on balance. Based on knowledge of the
      association between specific somatosensory loss and deterioration of balance,
      conclusions can be made about role of somatosensation in standing balance. A
      systematic literature review is presented in which publications from the years
      1993 through 2007 were searched in Medline and Embase. Medical Subject Headings
      (MESH) terms and free text words (related to balance, somatosensory loss, and
      lower limb) were used to perform the searches. Fifteen articles were selected for
      detailed review based on predetermined inclusion criteria, and three of the
      included articles described the effect of experimentally reduced somatosensation
      on balance in healthy subjects. Ten of the articles described balance in diabetic
      neuropathy (DN). The last two included articles described balance in Charcot
      Marie-Tooth (CMT) disease type 1A (CMT1A) or type 2 (CMT2). The literature
      indicates that the tactile sensation is reduced in DN, CMT1A, and CMT2 and when
      the plantar surface of the feet was hypothermically anesthetized. Joint motion
      sensation seems to be impaired in patients with DN, and passive joint position
      sensation appears to be reduced in healthy subjects with anesthesia of ankle and
      foot from prolonged ischemia. This reduced somatosensation seems to have a
      negative effect on balance in patients with DN and CMT2; however, this appeared
      not to be the case in patients with CMT1A and in healthy subjects.

PMID- 20144344
TI  - Computerized prompting and feedback of diabetes care: a review of the literature.
AB  - BACKGROUND: The objective of this study was to assess published literature on
      computerized prompting and feedback of diabetes care as well as to identify
      opportunities to strengthen diabetes care processes. METHODS: Medline (1970
      2008), Cumulative Index to Nursing and Allied Health Literature (1982-2008), and
      Cochrane Central Register of Controlled Trials (4th quarter 2008) were searched,
      and reference lists from included articles were reviewed to identify additional
      studies. Patient sample, clinician sample, setting, duration of the trial,
      intervention description, control description, and results were abstracted from
      each study. RESULTS: Fifteen trials were included in this review. The following
      elements were observed in the interventions: general prompt for a particular
      patient to be seen for diabetes-related follow-up (5 studies), specific prompt
      reminding clinicians of particular tests or procedures related to diabetes (13
      studies), feedback to clinicians in addition to prompting (5 studies), and
      patient reminders in addition to clinician prompts (5 studies). Twelve of the 15
      studies (80%) measured a significant process or outcome from the intervention.
      CONCLUSIONS: The majority of trials identified at least one process or outcome
      that was significantly better in the intervention group than in the control
      group; however, the success of the information interventions varied greatly.
      Providing and receiving appropriate care is the first step toward better outcomes
      in chronic disease management.

PMID- 20144345
TI  - Numerical and clinical accuracy of a continuous glucose monitoring system during
      intravenous insulin therapy in the surgical and burn intensive care units.
AB  - BACKGROUND: Intensive insulin therapy (IIT) for glycemic control in critically
      ill patients has been shown to be beneficial. Continuous glucose monitoring
      systems (CGMSs) have been approved as an adjunct to complement standard glucose
      monitoring in type 2 diabetes mellitus. This study was designed to evaluate the
      accuracy of a real-time CGMS (DexCom STS) in the intensive care unit (ICU). We
      also evaluated its reliability and accuracy using a hyperinsulinemic-euglycemic
      and a hyperglycemic clamp study. METHODS: Nineteen patients were enrolled in this
      7-day study [13 = surgical intensive care unit (SICU), 6 = burn intensive care
      unit (BICU)]. The patients were on IIT for at least 2 h prior the subcutaneous
      sensor insertion. Mean age and body mass index for SICU and BICU patients were
      60.3 +/- 3.7 and 64.5 +/- 6.2 years and 36.6 +/- 5.0 and 33.85 +/- 3.4 kg/m2,
      respectively. DexCom accuracy was analyzed separately for the Johnson & Johnson
      (J&J) calibration finger sticks, Roche Accucheck finger sticks, and the Hitachi
      917 analyzer measurements on serum using Clarke error grid analysis and Bland
      Altman analysis. In the clamp studies, 20 patients were enrolled, and the data
      were analyzed similarly. RESULTS: There were 1065 pairs of DexCom-Accucheck, 232
      pairs of DexCom-J&J, and 84 pairs of DexCom-Hitachi in ICU patients. For DexCom
      Accucheck, 68.26% of the pairs fell into zone A, 31.83% into zone B, and 0.75%
      into zone C. There were no values in zones D or E. From the 1102 matching DexCom
      Beckman pairs in clamp studies, 42.29% were in zone A, 55.90% were in zone B, and
      4.08% were in zone C. CONCLUSIONS: Despite the high percentage of measurements in
      zones A and B, underestimation of hypoglycemia by DexCom measurements makes it an
      unreliable device in the ICU setting.

PMID- 20144346
TI  - Analysis: Continuous glucose monitoring during intensive insulin therapy.
AB  - Results of the Normoglycemia in Intensive Care Evaluation and Survival Using
      Glucose Algorithm Regulation (NICE-SUGAR) trial, intensive insulin therapy (IIT),
      and use of a continuous glucose sensor in intensive care units (ICU) were
      analyzed. The NICE-SUGAR trial was unable to determine if optimal intensive
      insulin therapy decreases mortality. Continuous glucose monitoring (CGM)
      technology has the potential to improve glycemic control with low glucose
      variability and low incidence of hypoglycemia. Interstitial fluid CGM may not be
      useful in perioperative and ICU settings. Studies evaluating the accuracy and
      reliability of CGM devices, based on a whole blood sample in perioperative and
      ICU settings, are needed. Once a reliable CGM sensor for ICU use is identified, a
      large, prospective, controlled, multicenter study could determine if optimal IIT
      with a low or zero incidence of hypoglycemic events improves mortality.

PMID- 20144347
TI  - Gastric electrical stimulation with the TANTALUS System in obese type 2 diabetes
      patients: effect on weight and glycemic control.
AB  - BACKGROUND: The TANTALUS System is an investigational device that consists of an
      implantable pulse generator connected to gastric electrodes. The system is
      designed to automatically detect when eating starts and only then deliver
      sessions of gastric electrical stimulation (GES) with electrical pulses that are
      synchronized to the intrinsic antral slow waves. We report the effect of this
      type of GES on weight loss and glucose control in overweight/obese subjects with
      type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug
      Administration/Institutional Review Board-approved investigational device
      exemption. METHOD: Fourteen obese T2DM subjects on oral antidiabetes medication
      were enrolled and implanted laparoscopically with the TANTALUS System (body mass
      index 39 +/- 1 kg/m(2), hemoglobin A1c [HbA1c] 8.5 +/- 0.2%).Gastric electrical
      stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting
      blood glucose, blood pressure, and lipid levels were assessed during the study
      period. RESULTS: Eleven subjects reached the 6-month treatment period endpoint.
      Gastric electrical stimulation was well tolerated by all subjects. In those
      patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5
      +/- 0.7% to 7.6 +/- 1%, p < .01. Weight was also significantly reduced from 107.7
      +/- 21.1 to 102.4 +/- 20.5 kg, p < .01. The improvement in glucose control did
      not correlate with weight loss (R(2) = 0.05, p = .44). A significant improvement
      was noted in blood pressure, triglycerides, and cholesterol (low-density
      lipoprotein only). CONCLUSIONS: Short-term therapy with the TANTALUS System
      improves glucose control, induces weight loss, and improves blood pressure and
      lipids in obese T2DM subjects on oral antidiabetes therapy.

PMID- 20144348
TI  - Glucose meters: a review of technical challenges to obtaining accurate results.
AB  - Glucose meters are universally utilized in the management of hypoglycemic and
      hyperglycemic disorders in a variety of healthcare settings. Establishing the
      accuracy of glucose meters, however, is challenging. Glucose meters can only
      analyze whole blood, and glucose is unstable in whole blood. Technical accuracy
      is defined as the closeness of agreement between a test result and the true value
      of that analyte. Truth for glucose is analysis by isotope dilution mass
      spectrometry, and frozen serum standards analyzed by this method are available
      from the National Institute of Standards and Technology. Truth for whole blood
      has not been established, and cells must be separated from the whole blood matrix
      before analysis by a method like isotope dilution mass spectrometry. Serum cannot
      be analyzed by glucose meters, and isotope dilution mass spectrometry is not
      commonly available in most hospitals and diabetes clinics to evaluate glucose
      meter accuracy. Consensus standards recommend comparing whole blood analysis on a
      glucose meter against plasma/serum centrifuged from a capillary specimen and
      analyzed by a clinical laboratory comparative method. Yet capillary samples may
      not provide sufficient volume to test by both methods, and venous samples may be
      used as an alternative when differences between venous and capillary blood are
      considered. There are thus multiple complexities involved in defining technical
      accuracy and no clear consensus among standards agencies and professional
      societies on accuracy criteria. Clinicians, however, are more concerned with
      clinical agreement of the glucose meter with a serum/plasma laboratory result.
      Acceptance criteria for clinical agreement vary across the range of glucose
      concentrations and depend on how the result will be used in screening or
      management of the patient. A variety of factors can affect glucose meter results,
      including operator technique, environmental exposure, and patient factors, such
      as medication, oxygen therapy, anemia, hypotension, and other disease states.
      This article reviews the challenges involved in obtaining accurate glucose meter
      results.

PMID- 20144349
TI  - Continuous glucose monitoring and clinical trials.
AB  - The use of glucose sensors during clinical trials seems like a great idea at
      first glance. Continuous glucose monitoring (CGM) should allow the gathering of
      more detailed information about metabolic control, without requiring much
      additional effort. In principle, CGM can reduce the duration of such studies and
      the number of participants required. The aim of this commentary is to highlight
      some of the reasons why, in practice, at least some of these hopes have not been
      realized. It is not only that a new technology requires extensive training of the
      study personnel; the practical handling of the devices and the time and effort
      required to download and analyze the data are often grossly underestimated
      initially. In addition, one must select the best endpoints for describing the
      level of metabolic control in view of the overwhelming amount of information
      provided by CGM. Several measures and endpoints were proposed as (potential)
      parameters that would be more meaningful than the standard parameters currently
      used to describe glucose profiles. Unfortunately, most of these proposed
      parameters have not, as yet, been proven to be more meaningful. Calibration is
      another critical aspect of using CGM that must be addressed. How this procedure
      is handled in practice has a profound impact on the quality of the glucose
      recordings. Finally, shall the current measurement results be displayed to the
      study participant or not? CGM can help prevent severe hypoglycemic episodes, but
      this can profoundly affect the study outcome in a manner that is unrelated to
      basic aim of the study (e.g., comparing medications that are designed to control
      glycemia). Therefore, the use of CGM in clinical trials requires much more
      careful consideration than was initially thought.

PMID- 20144350
TI  - Sources of glycemic variability--what type of technology is needed?
AB  - People on insulin therapy are challenged with evaluation of numerous factors
      affecting the blood glucose in order to select the optimal dose for reaching
      their glucose target. Following medical recommendations precisely still results
      in considerable blood glucose unpredictability, often resulting in frustration in
      the short term due to hypoglycemia and hyperglycemia, and, in the long term, will
      likely result in complications. The kinetics of insulin do indeed vary
      significantly and have become an important focus when developing new insulin
      analogues and delivery systems; however, numerous of other factors impact
      glycemic variability. These have different dependences and interactions and are
      therefore difficult to characterize. Some of the factors are highly dependent and
      influenced by the type of insulin and devices used in therapy. Development of
      future therapy products is therefore highly focused on how to minimize glycemic
      variability.

PMID- 20144351
TI  - The role of reimbursement in the adoption of continuous glucose monitors.
AB  - Continuous glucose monitors are a clinically meaningful addition to treatment
      plans for patients with diabetes who are actively managing their care. Since they
      first became commercially available, much progress has been made to ensure
      coverage of these devices for patients, but inadequate reimbursement of
      clinicians' time continues to serve as a barrier to adoption.

PMID- 20144352
TI  - Glutamic Acid decarboxylase therapy for recent-onset type 1 diabetes: are we at
      the end or the beginning of finding a cure?

PMID- 20144353
TI  - Near-infrared microspectroscopic analysis of rat skin tissue heterogeneity in
      relation to noninvasive glucose sensing.
AB  - BACKGROUND: Noninvasive glucose measurements are possible by analysis of
      transmitted near-infrared light over the 4000- to 5000-cm(-1) spectral range.
      Such measurements are highly sensitive to the exact position of the fiber-optic
      interface on the surface of the skin sample. A critical question is the degree of
      heterogeneity of the major chemical components of the skin matrix in relation to
      the size of the fiber-optic probed used to collect noninvasive spectra.
      Microscopic spectral mapping is used to map the chemical distribution for a set
      of excised sections of rat skin. METHOD: A Fourier transform near-infrared
      microspectrometer was used to collect transmission spectra from 16 tissue samples
      harvested from a set of four healthy Harlan-Sprague male rats. A reference point
      in the center of the tissue sample was probed regularly to track dehydration,
      changes in tissue composition, and changes in instrument performance. Amounts of
      the major skin constituents were determined by fitting microspectra to a set of
      six pure component absorbance spectra corresponding to water, type I collagen
      protein, keratin protein, fat, an offset term, and a slope term. RESULTS:
      Microspectroscopy provides spectra with root mean square noise levels on 100%
      lines between 418 and 1475 microabsorbance units, which is sufficient for
      measuring the main chemical components of skin. The estimated spatial resolution
      of the microscope is 220 microm. The amounts of each tissue matrix component were
      determined for each 480 x 360-microm(2) location of a 4.8 x 3.6-mm(2) rectangular
      block of skin tissue. These spectra were used to generate two-dimensional
      distribution maps for each of the principal skin components. CONCLUSIONS:
      Distribution of the chemical components of rat skin is significant relative to
      the dimensions of noninvasive glucose sensing. Chemical distribution maps reveal
      that variations in the chemical composition of the skin samples are on the same
      length scale as the fiber-optic probe used to collect noninvasive near-infrared
      spectra. Analysis of variance between tissue slices collected for one animal and
      analysis of variations between animals indicate that animal-to-animal variation
      for all four chemical components is significantly higher than variations between
      samples for a given animal. These findings justify the collection and
      interpretation of near-infrared microspectroscopic maps of human skin to
      establish chemical heterogeneity and its impact on noninvasive glucose sensing
      for the management of diabetes.

PMID- 20144354
TI  - Requirements for calibration in noninvasive glucose monitoring by Raman
      spectroscopy.
AB  - BACKGROUND: In the development of noninvasive glucose monitoring technology, it
      is highly desirable to derive a calibration that relies on neither person
      dependent calibration information nor supplementary calibration points furnished
      by an existing invasive measurement technique (universal calibration). METHOD: By
      appropriate experimental design and associated analytical methods, we establish
      the sufficiency of multiple factors required to permit such a calibration.
      Factors considered are the discrimination of the measurement technique,
      stabilization of the experimental apparatus, physics-physiology-based measurement
      techniques for normalization, the sufficiency of the size of the data set, and
      appropriate exit criteria to establish the predictive value of the algorithm.
      RESULTS: For noninvasive glucose measurements, using Raman spectroscopy, the
      sufficiency of the scale of data was demonstrated by adding new data into an
      existing calibration algorithm and requiring that (a) the prediction error should
      be preserved or improved without significant re-optimization, (b) the complexity
      of the model for optimum estimation not rise with the addition of subjects, and
      (c) the estimation for persons whose data were removed entirely from the training
      set should be no worse than the estimates on the remainder of the population.
      Using these criteria, we established guidelines empirically for the number of
      subjects (30) and skin sites (387) for a preliminary universal calibration. We
      obtained a median absolute relative difference for our entire data set of 30
      mg/dl, with 92% of the data in the Clarke A and B ranges. CONCLUSIONS: Because
      Raman spectroscopy has high discrimination for glucose, a data set of practical
      dimensions appears to be sufficient for universal calibration. Improvements based
      on reducing the variance of blood perfusion are expected to reduce the prediction
      errors substantially, and the inclusion of supplementary calibration points for
      the wearable device under development will be permissible and beneficial.

PMID- 20144355
TI  - Single walled carbon nanotubes as reporters for the optical detection of glucose.
AB  - This article reviews current efforts to make glucose sensors based on the
      inherent optical properties of single walled carbon nanotubes. The advantages of
      single walled carbon nanotubes over traditional organic and nanoparticle
      fluorophores for in vivo-sensing applications are discussed. Two recent glucose
      sensors made by our group are described, with the first being an enzyme-based
      glucose sensor that couples a reaction mediator, which quenches nanotube
      fluorescence, on the surface of the nanotube with the reaction of the enzyme. The
      second sensor is based on competitive equilibrium binding between dextran-coated
      nanotubes and concanavalin A. The biocompatibility of a model sensor is examined
      using the chicken embryo chorioallantoic membrane as a tissue model. The
      advantages of measuring glucose concentration directly, like most optical
      sensors, versus measuring the flux in glucose concentration, like most
      electrochemical sensors, is discussed.

PMID- 20144356
TI  - Noninvasive glucose monitoring: a novel approach.
AB  - BACKGROUND: The main concern in noninvasive (NI) glucose measurement is achieving
      high accuracy readings, although no blood (or other fluid) is involved in the
      process. Using methods based on different physical properties of a measured
      object can ensure the independence of each of the readings and therefore improve
      the validity of the end result. By using a combination of (three) independent
      technologies-ultrasonic, electromagnetic, and thermal-GlucoTrack presents a
      unique approach for a real-time, truly NI blood glucose spot measurement.
      METHODS: Clinical trials were performed in two stages. Stage 1 was an initial
      method validation and performance verification of the device. In this stage, 50
      type 1 and 2 diabetic patients, as well as healthy subjects, were evaluated with
      GlucoTrack against Ascensia Elite (Bayer). In the second stage, 85 additional
      diabetic subjects were evaluated in half and full daytime sessions using a
      GlucoTrack comparison with HemoCue (Glucose 201+). RESULTS: A total of 135
      subjects were tested during the trial period, producing 793 data pairs. Using
      Clarke error grid analysis, 92% of the readings fell in the clinically acceptable
      zones A and B, with 50% in the A zone. Mean and median relative absolute
      differences were 29.9 and 19.9%, respectively. CONCLUSIONS: Integrating several
      modalities for NI assessment of glucose level enables more accurate readings,
      while a possible aberration in one modality is bypassed by the others. The
      present generation of GlucoTrack gives promising results; however, further
      improvement of the accuracy of the device is needed.

PMID- 20144357
TI  - Temporal and geographic patterns of hypoglycemia among hospitalized patients with
      diabetes mellitus.
AB  - BACKGROUND: Hypoglycemia is often cited as a barrier to achieving inpatient
      glycemic targets. We sought to characterize hypoglycemic events in our
      institution by work-shift cycle and by specific treatment area. METHODS:
      Capillary (bedside) and blood (laboratory) glucose values of <70 mg/dl for
      patients with either a known diagnosis of diabetes or with evidence of
      hyperglycemia were abstracted from our laboratory database for hospitalizations
      between October 1, 2007, and February 3, 2008. Hypoglycemic events were analyzed
      by 12 h nursing work-shift cycles (day shift, 07:00 to 18:59; night shift, 19:00
      to 06:59) and by the six medical, surgical, and intensive care areas in the
      hospital (designated areas 1 to 6). RESULTS: We identified 206 individual
      patients with either diabetes or hyperglycemia (mean age, 67 years; 56% men; 83%
      white) who had 423 hypoglycemic events. There were 78% more hypoglycemic events
      during the night shift (n = 271 events in 128 individual patients) than during
      the day shift (n = 152 events in 96 individual patients). Most of the night-shift
      hypoglycemic measurements were detected between 04:00 and 04:59 or 06:00 and
      06:59. The mean hypoglycemic level was comparable between shifts (p = .79) and
      across the six inpatient areas. The number of hypoglycemic events per person
      increased with lengths of hospital stay >5 days. The prevalence of hypoglycemia
      varied across patient care areas within the hospital, with most (28%) detected in
      one area of the hospital. CONCLUSION: There are temporal and geographic patterns
      in the occurrence of hypoglycemia among patients with diabetes or hyperglycemia
      in our hospital. Further study should focus on the reasons underlying these
      variations so that specific interventions can address the risk of hypoglycemia
      during peak times and places.

PMID- 20144358
TI  - In silico preclinical trials: methodology and engineering guide to closed-loop
      control in type 1 diabetes mellitus.
AB  - This article sets forth guidelines for in silico (simulation-based) proof-of
      concept testing of artificial pancreas control algorithms. The goal was to design
      a test procedure that can facilitate regulatory approval [e.g., Food and Drug
      Administration Investigational Device Exemption] for General Clinical Research
      Center experiments without preliminary testing on animals. The methodology is
      designed around a software package, based on a recent meal simulation model of
      the glucose-insulin system. Putting a premium on generality, this document starts
      by specifying a generic, rather abstract, meta-algorithm for control. The meta
      algorithm has two main components: (1) patient assessment and tuning of control
      parameters, i.e., algorithmic processes for collection and processing patient
      data prior to closed-loop operation, and (2) controller warm-up and run-time
      operation, i.e., algorithmic processes for initializing controller states and
      managing blood glucose. The simulation-based testing methodology is designed to
      reveal the conceptual/mathematical operation of both main components, as applied
      to a large population of in silico patients with type 1 diabetes mellitus.

PMID- 20144359
TI  - Eliminating the blood: ongoing outbreaks of hepatitis B virus infection and the
      need for innovative glucose monitoring technologies.
AB  - BACKGROUND: As part of routine diabetes care, capillary blood is typically
      sampled using a finger-stick device and then tested using a handheld blood
      glucose meter. In settings where multiple persons require assistance with blood
      glucose monitoring, opportunities for bloodborne pathogen transmission may exist.
      METHODS: Reports of hepatitis B virus (HBV) infection outbreaks in the United
      States that have been attributed to blood glucose monitoring practices were
      reviewed and summarized. RESULTS: Since 1990, state and local health departments
      investigated 18 HBV infection outbreaks, 15 (83%) in the past 10 years, that were
      associated with the improper use of blood glucose monitoring equipment. At least
      147 persons acquired HBV infection during these outbreaks, 6 (4.1%) of whom died
      from complications of acute HBV infection. Outbreaks appear to have become more
      frequent in the past decade, primarily affecting long-term care residents with
      diabetes. Each outbreak was attributed to glucose monitoring practices that
      exposed HBV-susceptible persons to blood-contaminated equipment that was
      previously used on HBV-infected persons. The predominant unsafe practices were
      the use of spring-loaded finger-stick devices on multiple persons and the sharing
      of blood glucose testing meters without cleaning and disinfection between uses.
      CONCLUSION: Hepatitis B virus infection outbreaks associated with blood glucose
      monitoring have occurred with increasing regularity in the Unites States and may
      represent a growing but under-recognized problem. Advances in technology, such as
      the development of blood glucose testing meters that can withstand frequent
      disinfection and noninvasive glucose monitoring methods, will likely prove useful
      in improving patient safety.

PMID- 20144360
TI  - Improving access to eye care: teleophthalmology in Alberta, Canada.
AB  - BACKGROUND: Diabetic retinopathy in Alberta and throughout Canada is common, with
      a prevalence up to 40% in people with diabetes. Unfortunately, due to travel
      distance, time, and expense, a third of patients with diabetes do not receive
      annual dilated eye examinations by ophthalmologists, despite universal health
      care access. In an effort to improve access, a teleophthalmology program was
      developed to overcome barriers to eye care. Prior to clinical implementation,
      teleophthalmology technology was clinically validated for the identification of
      treatable levels of diabetic retinopathy. METHOD: Patients undergoing a
      teleophthalmology assessment underwent stereoscopic digital retinal photographs
      following pupillary dilation. Digital images were then packaged into an encrypted
      password-protected compressed file for uploading onto a secure server. Images
      were digitally unpackaged for review as a stereoscopic digital slide show and
      graded with a modified Early Treatment Diabetic Retinopathy Study algorithm.
      Reports were then generated automatically as a PDF file and sent back to the
      referring physician. RESULTS: Teleophthalmology programs in Alberta have assessed
      more than 5500 patients (9016 visits) to date. Nine hundred thirty patients have
      been referred for additional testing or treatment. Approximately 2% of
      teleophthalmology assessments have required referral for in-person examination
      due to ungradable image sets, most commonly due to cataract, corneal drying, or
      asteroid hyalosis. CONCLUSIONS: In Alberta and throughout Canada, many patients
      with diabetes do not receive an annual dilated eye examination. Teleophthalmology
      is beneficial because patients can be assessed within their own communities. This
      decreases the time to treatment, allows treated patients to be followed remotely,
      and prevents unnecessary referrals. Health care costs may be reduced by the
      introduction of comprehensive teleophthalmology examinations by enabling testing
      and treatment to be planned prior to the patient's first visit.

PMID- 20144361
TI  - Fabrication of polymer microneedles using a two-photon polymerization and
      micromolding process.
AB  - BACKGROUND: Microneedle-mediated drug delivery is a promising method for
      transdermal delivery of insulin, incretin mimetics, and other protein-based
      pharmacologic agents for treatment of diabetes mellitus. One factor that has
      limited clinical application of conventional microneedle technology is the poor
      fracture behavior of microneedles that are created using conventional materials
      and methods. In this study polymer microneedles for transdermal delivery were
      created using a two-photon polymerization (2PP) microfabrication and subsequent
      polydimethylsiloxane (PDMS) micromolding process. METHODS: Solid microneedle
      arrays, fabricated by means of 2PP, were used to create negative molds from PDMS.
      Using these molds microneedle arrays were subsequently prepared by molding eShell
      200, a photo-reactive acrylate-based polymer that exhibits water and perspiration
      resistance. RESULTS: The eShell 200 microneedle array demonstrated suitable
      compressive strength for use in transdermal drug delivery applications. Human
      epidermal keratinocyte viability on the eShell 200 polymer surfaces was similar
      to that on polystyrene control surfaces. In vitro studies demonstrated that
      eShell 200 microneedle arrays fabricated using the 2PP microfabrication and PDMS
      micromolding process technique successfully penetrated human stratum corneum and
      epidermis. CONCLUSIONS: Our results suggest that a 2PP microfabrication and
      subsequent PDMS micromolding process may be used to create microneedle structures
      with appropriate structural, mechanical, and biological properties for
      transdermal drug delivery of insulin and other protein-based pharmacologic agents
      for treatment of diabetes mellitus.

PMID- 20144362
TI  - Comparison of intuitiveness, ease of use, and preference in two insulin pens.
AB  - BACKGROUND: The intuitiveness, instruction time, and handling of the Levemir
      (insulin detemir) FlexPen and the Lantus OptiClik pen (with insulin glargine)
      were investigated. METHODS: This randomized open-label crossover study involved
      two groups of insulin-device-naive Japanese patients with type 2 diabetes [mean
      (SD) age 61.9 +/- 12.3 years, 57% male]. Patients were evaluated on the ease-of
      use of each insulin pen without instruction [intuitiveness group (n = 32)], or
      with instruction [instruction time group (n = 29)]. Patient preferences for the
      respective devices were assessed by questionnaire. RESULTS AND DISCUSSION:
      FlexPen required significantly less instruction time (p < .001) and was
      objectively more intuitive to use (p < .001) than OptiClik. Nevertheless, few
      patients in the intuitiveness group felt confident injecting either pen prior to
      instruction (FlexPen, 31%; OptiClik, 16%). No patients in the instruction time
      group found FlexPen difficult to learn, whereas 45% of patients found OptiClik
      difficult or very difficult to learn. FlexPen was rated simpler to use (77%
      versus 12%; p < .001), easier to inject (67% versus 13%; p < .001), and more
      convenient (71% versus 12%; p < .001) compared with OptiClik. More patients would
      trust FlexPen to deliver insulin injections (p < .01) and would prefer to use
      FlexPen compared with OptiClik (82% versus 13%; p < .001). CONCLUSIONS: FlexPen
      was faster to teach, simpler to use, and more trusted by patients compared with
      OptiClik. Mean injection time was significantly shorter for FlexPen than
      OptiClik, with or without instruction. This study highlights not only how easy it
      is for patients to learn to use FlexPen, but also how easily health care
      providers can teach patients to use it.

PMID- 20144364
TI  - Evaluation of current literature to determine the potential effects of radio
      frequency identification on technology used in diabetes care.
AB  - This article examines recently published studies exploring the impact of radio
      frequency identification (RFID) systems on the technology involved in patient
      care. The conclusions will be extrapolated to include insulin delivery devices.
      Background material will also be presented to support examination of the
      variables involved in electromagnetic fields and potential interference from
      these RFID systems.

PMID- 20144363
TI  - The role of immunomodulation therapy in autoimmune diabetes.
AB  - Type 1 diabetes (T1DM) is characterized by loss of virtually all endogenous
      insulin secretion. If residual insulin secretion is preserved, this will lead to
      improved metabolic balance, less acute and late complications, improved quality
      of life, and, in case of pronounced improvement of residual insulin secretion,
      complete remission and even cure of the disease. Immune suppression or immune
      modulation have been demonstrated as a proof of principle to stop/decrease the
      destructive process and thereby preserve beta-cell function. Several methods to
      save residual beta-cell function have been tried for more than three decades with
      little or no evidence of efficacy. Positive effects have been seen mainly in
      adult patients but have been minimal or absent in children with diabetes.
      Furthermore, the safety of these immune interventions and/or their benefit to
      risk relationships have not been found to justify clinical use. More specific
      immune modulation with anti-CD3 monoclonal antibodies has resulted in more
      encouraging postponement of C-peptide decline, but with frequent and serious
      adverse effects. Still more promising are the autoantigen therapies, of which
      glutamic acid decarboxylase (GAD) vaccination has shown significant preservation
      of residual insulin secretion in 10-18-year-old type 1 diabetes patients with
      recent onset. Efficacy was most impressive in the subgroup of patients with
      diabetes of short duration (<3 months). The treatment was simple, well tolerated,
      and showed no treatment-related adverse events. If these results can be
      confirmed, there is a realistic hope that GAD vaccination, perhaps in combination
      with vaccinations with other autoantigens and/or other therapies, will result in
      remission for some patients. The prospects of cure and prevention of T1DM will
      become less remote.

PMID- 20144365
TI  - Maggot therapy takes us back to the future of wound care: new and improved maggot
      therapy for the 21st century.
AB  - In the 21st century, eighty years after William Baer presented his groundbreaking
      work treating bone and soft tissue infections with live maggots, thousands of
      therapists around the globe have rediscovered the benefits of maggot therapy. The
      renaissance in maggot therapy is due in large part to recent technological
      advancements that have solved or minimized many of the treatment's earlier
      drawbacks: the need for reliable access to this perishable medical device,
      simplified application, and low-cost production. Modern dressing materials have
      simplified the procedure and minimized the risk of escaping maggots. The
      establishment of dozens of laboratories throughout the world, along with access
      to overnight courier services in many regions, has made medicinal maggots readily
      available to millions of people in need. Studies show that fears of patient
      nonacceptance are unfounded. The medical literature is rapidly growing with
      scientific evidence demonstrating the efficacy and safety of maggot therapy for a
      variety of problematic wounds. This article examines how these and other
      technologies are optimizing the study and application of maggot therapy for wound
      care.

PMID- 20144366
TI  - Diabetes connected health: a pilot study of a patient- and provider-shared
      glucose monitoring web application.
AB  - BACKGROUND: Real-time sharing of blood glucose results with providers could
      improve communication and lead to more timely medication titration. New
      technology platforms are available to support the delivery of innovative models
      of care delivery. METHODS: In the Diabetes Connected Health (DCH) pilot study,
      patients with diabetes received access to an online application that stored and
      graphed glucose readings uploaded from a standard glucometer. Both patients and
      providers had access to this Web site, where data could be viewed, analyzed, and
      discussed. To examine the impact of the DCH program, we assessed adoption of the
      program, patient and provider satisfaction, frequency of use, and changes in
      glucose levels over a period of 3 months. RESULTS: The mean age of the 7 pilot
      participants was 51 (range 35-65). Participants sent in an average of 50 readings
      in Month 1 and 38 readings in Month 3 and made, on average, 6 comments in Months
      1 and 12 comments in Month 3. The mean blood glucose range decreased in Month 3
      versus Month 1 (141.1 and 146.5, respectively). Self-reported HbA1c fell from
      6.8% at the start of the study to 5.8% at the end. Five/seven participants
      described the site as excellent or good. Qualitative data analysis highlighted
      key benefits of the program as well as areas for improvement. CONCLUSIONS: This
      pilot study of a shared glucose monitoring Web application was well received by
      patients. Programs like this may lead to improvements in the quality of clinical
      care delivered to people with type 2 diabetes.

PMID- 20144367
TI  - Toward an agent-based patient-physician model for the adoption of continuous
      glucose monitoring technology.
AB  - Health care is a major component of the U.S. economy, and tremendous research and
      development efforts are directed toward new technologies in this arena.
      Unfortunately few tools exist for predicting outcomes associated with new medical
      products, including whether new technologies will find widespread use within the
      target population. Questions of technology adoption are rife within the diabetes
      technology community, and we particularly consider the long-term prognosis for
      continuous glucose monitoring (CGM) technology. We present an approach to the
      design and analysis of an agent model that describes the process of CGM adoption
      among patients with type 1 diabetes mellitus (T1DM), their physicians, and
      related stakeholders. We particularly focus on patient-physician interactions,
      with patients discovering CGM technology through word-of-mouth communication and
      through advertising, applying pressure to their physicians in the context of CGM
      device adoption, and physicians, concerned about liability, looking to peers for
      a general level of acceptance of the technology before recommending CGM to their
      patients. Repeated simulation trials of the agent-based model show that the
      adoption process reflects the heterogeneity of the adopting community. We also
      find that the effect of the interaction between patients and physicians is
      agents. Each physician, say colored by the nature of the environment as defined
      by the model parameters. We find that, by being able to represent the diverse
      perspectives of different types of stakeholders, agent-based models can offer
      useful insights into the adoption process. Models of this sort may eventually
      prove to be useful in helping physicians, other health care providers, patient
      advocacy groups, third party payers, and device manufacturers understand the
      impact of their decisions about new technologies.

PMID- 20144368
TI  - Unlocking the potential of continuous glucose monitoring: a new guideline
      supports the development of continuous glucose monitoring devices.
AB  - Continuous glucose monitoring (CGM) is a new technology that allows patients to
      measure glucose levels continuously over several days. It has several advantages
      over traditional glucose meters in that it does not involve repeated finger
      sticks and can measure trends and track changes in glucose levels over time. The
      Clinical and Laboratory Standards Institute, working with the Diabetes Technology
      Society, published Performance Metrics for Continuous Interstitial Glucose
      Monitoring; Approved Guideline, which provides recommendations for methods for
      determining analytical and clinical metrics of CGMs. The document provides
      guidance on how CGM data should be presented, compared between devices, and
      compared between measurement technologies. The document serves as a roadmap for
      the testing of CGM devices and will ultimately advance the potential of this
      exciting technology. Performance Metrics for Continuous Interstitial Glucose
      Monitoring; Approved Guideline represents the consensus view on preparing and
      presenting CGM data.

PMID- 20144369
TI  - Eating for life: designing foods for appetite control.
AB  - We are all well aware that rising levels of obesity in developed countries is
      having a significant impact on the health of the population. This is despite the
      availability of a wide range of low-calorie foods and an awareness of how
      important it is to adopt a healthy lifestyle. A new and emerging approach is to
      design foods that enhance the physiological regulatory mechanisms controlling
      appetite and energy intake. This is achieved through either promoting gastric
      distension or slowing intestinal transit in order to promote satiety-enhancing
      neuroendocrine feedback responses. This commentary explores the background and
      mechanisms involved in developing these strategies.

PMID- 20144370
TI  - Insulin-like growth factor-I as a candidate metabolic biomarker: military
      relevance and future directions for measurement.
AB  - Insulin-like growth factor (IGF)-I is a ubiquitous peptide hormone involved in a
      host of critical physiological processes (e.g., protein synthesis and glucose
      homeostasis) and has been suggested to be a biomarker reflecting health and
      metabolic status. In most cases (muscle, bone, tendon, body composition, and
      cognitive function), elevated IGF-I concentrations are considered beneficial;
      however, cancer remains a notable exception. While the fact that both increased
      and decreased IGF-I can be considered reflective of favorable and beneficial
      health outcomes may appear as a paradox, it is important to emphasize that, in
      both cases, measured IGF-I concentrations do offer important insight into
      physiological processes. The effects of military operational field training on
      the circulating IGF-I system are discussed within the context of novel
      measurement technologies that (1) are field expedient and (2) provide more
      meaningful information. Prospective experimental approaches involving physical
      activity that sample and measure IGF-I in the body's various biocompartments will
      provide greater insight into the complex role that IGF-I possesses. Minimally
      invasive technologies that are field expedient, cost-effective, and allow for
      continuous and real-time feedback will have the greatest likelihood of being
      adapted and used in military environments.

PMID- 20144371
TI  - Mathematical modeling research to support the development of automated insulin
      delivery systems.
AB  - The world leaders in glycemia modeling convened during the Eighth Annual Diabetes
      Technology Meeting in Bethesda, Maryland, on 14 November 2008, to discuss the
      current practices in mathematical modeling and make recommendations for its use
      in developing automated insulin-delivery systems. This report summarizes the
      collective views of the 25 participating experts in addressing the following four
      topics: current practices in modeling efforts for closed-loop control; framework
      for exchange of information and collaboration among research centers; major
      barriers for the development of accurate models; and key tasks for developing
      algorithms to build closed-loop control systems. Among the participants, the
      following main conclusions and recommendations were widely supported: 1.
      Physiologic variance represents the single largest technical challenge to
      creating accurate simulation models. 2. A Web site describing different models
      and the data supporting them should be made publically available, with funding
      agencies and journals requiring investigators to provide open access to both
      models and data. 3. Existing simulation models should be compared and contrasted,
      using the same evaluation and validation criteria, to better assess the state of
      the art, understand any inherent limitations in the models, and identify gaps in
      data and/or model capability.

PMID- 20144372
TI  - Insulin pump safety meeting: summary report.
AB  - Diabetes Technology Society convened a panel of insulin pump experts in Bethesda,
      Maryland, on November 12, 2008, at the request of the Food and Drug
      Administration. The group consisted of physicians, nurses, diabetes educators,
      and engineers from across the United States. The panel members (1) discussed
      safety features of insulin pump therapy and (2) recommended adjustments to
      current insulin pump design and use to enhance overall safety. Software and
      hardware features of insulin pumps were analyzed from engineering, medical,
      nursing, and pump-user perspectives. The meeting was divided into four sections:
      (1) Engineering Safety-Designing Software and Hardware for Insulin Pump Therapy;
      (2) Patient Safety-Selecting Patients and Clinical Settings for Insulin Pump Use;
      (3) Clinical Safety-Determining and Delivering Insulin Dosages Using Insulin Pump
      Therapy; and (4) Personal Experiences-A Panel Discussion about Insulin Pump
      Safety. Six aspects of insulin pump technology were noted to present potential
      safety problems: (1) software, (2) wireless communication, (3) hardware, (4)
      alarms, (5) human factors, and (6) bolus-dose calculation. There was consensus
      among meeting participants that insulin pump therapy is beneficial in patients of
      all ages and that insulin pump safety must be assured through careful regulation.

PMID- 20144373
TI  - Comparison of continuous subcutaneous insulin infusion versus basal/bolus insulin
      injections for treatment of type 1 diabetes in clinical practice.

PMID- 20144374
TI  - Predicting postprandial glucose excursions using gaussian process regression.

PMID- 20144375
TI  - The beneficial effects of a Paleolithic diet on type 2 diabetes and other risk
      factors for cardiovascular disease.

PMID- 20144376
TI  - Pilot evaluation of a prototype critical care blood glucose monitor in normal
      volunteers.
AB  - BACKGROUND: Availability of a highly accurate in-hospital automated blood glucose
      (BG) monitor could facilitate implementation of intensive insulin therapy
      protocols through effective titration of insulin therapy, improved BG control,
      and avoidance of hypoglycemia. We evaluated a functional prototype BG monitor
      designed to perform frequent automated blood sampling for glucose monitoring.
      METHODS: Sixteen healthy adult volunteer subjects had intravenous catheter
      insertions in a forearm or hand vein and were studied for 8 hours. The prototype
      monitor consisted of an autosampling unit with a precise computer-controlled
      reversible syringe pump and a glucose analytical section. BG was referenced
      against a Yellow Springs Instrument (YSI) laboratory analyzer. Sampling errors
      for automated blood draws were assessed by calculating the percent of failed
      draws, and BG data were analyzed using the Bland and Altman technique. RESULTS:
      Out of 498 total sample draws, unsuccessful draws were categorized as follow: 11
      (2.2%) were due to autosampler technical problems, 21 (4.2%) were due to catheter
      related failures, and 37 (7.4%) were BG meter errors confirmed by a glucometer
      generated error code. Blood draw difficulties or failures related to the catheter
      site (e.g., catheter occlusion or vein collapse) occurred in 6/15 (40%) subjects.
      Mean BG bias versus YSI was 0.20 +/- 12.6 mg/dl, and mean absolute relative
      difference was 10.4%. CONCLUSIONS: Automated phlebotomy can be performed in
      healthy subjects using this prototype BG monitor. The BG measurement technology
      had suboptimal accuracy based on a YSI reference. A more accurate BG point-of
      care testing meter and strip technology have been incorporated into the future
      version of this monitor. Development of such a monitor could alleviate the burden
      of frequent BG testing and reduce the risk of hypoglycemia in patients on insulin
      therapy.

PMID- 20144377
TI  - An overview of hypoglycemia in the critically ill.
AB  - Hypoglycemia is a common and serious problem among patients with diabetes
      mellitus. It is also perceived as the most important obstacle to tight glucose
      control using intensive insulin therapy in critically ill patients. Because
      glucose is an obligatory metabolic fuel for the brain, hypoglycemia always
      represents an emergency that signals the inability of the brain to meet its
      energy needs. When left untreated, hypoglycemia can result in permanent brain
      damage and ultimately, death. In the context of critical illness that limits
      endogenous glucose production and increases glucose utilization, inadequate
      nutrition, or insufficient provision of glucose, intensive insulin therapy is the
      most frequent cause of hypoglycemia. Neurogenic and neuroglycopenic symptoms of
      hypoglycemia can remain unknown because of the underlying critical illness and
      sedation. Thus, close and reliable monitoring of the glycemic level is crucial in
      detecting hypoglycemia. In prospective randomized controlled studies comparing
      the effects of two glucose regimens, intensive insulin therapy aimed to reach
      strict glucose control (<110 mg/dl) but increased the incidence of severe
      hypoglycemia (<40 mg/dl) by four- to sixfold. Severe hypoglycemia is
      statistically associated with adverse outcomes in intensive care unit patients,
      although a direct causal relationship has not been demonstrated.

PMID- 20144378
TI  - Hyperglycemia in critical illness: a review.
AB  - Hyperglycemia is commonplace in the critically ill patient and is associated with
      worse outcomes. It occurs after severe stress (e.g., infection or injury) and
      results from a combination of increased secretion of catabolic hormones,
      increased hepatic gluconeogenesis, and resistance to the peripheral and hepatic
      actions of insulin. The use of carbohydrate-based feeds, glucose containing
      solutions, and drugs such as epinephrine may exacerbate the hyperglycemia.
      Mechanisms by which hyperglycemia cause harm are uncertain. Deranged osmolality
      and blood flow, intracellular acidosis, and enhanced superoxide production have
      all been implicated. The net result is derangement of endothelial, immune and
      coagulation function and an association with neuropathy and myopathy. These
      changes can be prevented, at least in part, by the use of insulin to maintain
      normoglycemia.

PMID- 20144379
TI  - An overview of preoperative glucose evaluation, management, and perioperative
      impact.
AB  - Perioperative hyperglycemia is a common phenomenon affecting patients both with
      and without a known prior history of diabetes. Despite an exponential rise in
      publications and studies of inpatient hyperglycemia over the last decade, many
      questions still exist as to what defines optimal care of these patients. Initial
      enthusiasm for tight glycemic control has waned as the unanticipated reality of
      hypoglycemia and mortality has been realized in some prospective studies. The
      recent dramatic modification of national practice guidelines to endorse more
      modest inpatient glycemic targets highlights the dynamic nature of current
      knowledge as the next decade approaches. This review discusses perioperative
      hyperglycemia and the categories of patients affected by it. It reviews current
      recommendations for ambulatory diabetes screening and its importance in
      preoperative patient care. Finally, it concludes with a review of current
      practice guidelines, as well as a discussion of future direction and goals for
      inpatient perioperative glycemic control.

PMID- 20144380
TI  - Challenges to glycemic measurement in the perioperative and critically ill
      patient: a review.
AB  - Accurate monitoring of glucose in the perioperative environment has become
      increasingly important over the last few years. Because of increased cost,
      turnaround time, and sample volume, the use of central laboratory devices for
      glucose measurement has been somewhat supplanted by point-of-care (POC) glucose
      devices. The trade-off in moving to these POC systems has been a reduction in
      accuracy, especially in the hypoglycemic range. Furthermore, many of these POC
      devices were originally developed, marketed, and received Food and Drug
      Administration regulatory clearance as home use devices for patients with
      diabetes. Without further review, many of these POC glucose measurement devices
      have found their way into the hospital environment and are used frequently for
      measurement during intense insulin therapy, where accurate measurements are
      critical. This review covers the technology behind glucose measurement and the
      evidence questioning the use of many POC devices for perioperative glucose
      management.

PMID- 20144381
TI  - Perioperative blood glucose monitoring in the general surgical population.
AB  - Several studies have shown a relationship between poor outcome and uncontrolled
      blood glucose (BG) in cardiac, neurosurgical, critical care, and general surgical
      patients. A major study showed that tight glycemic control (80-110mg/dl) was
      related to increased mortality. Based on evidence from controlled studies, the
      American Diabetes Association, and the Society of Thoracic Surgeons, maintaining
      intraoperative BG levels in the 140-180 mg/dl range seems appropriate.
      Optimization of the patient's preoperative medications and the use of insulin
      infusions, as well as surgical and anesthetic technique, are important factors
      for achieving desirable perioperative BG control. Minimizing BG variability
      during surgery should be part of the glycemic control strategy. Advances in real
      time glucose monitoring may soon benefit hospitalized diabetes and nondiabetes
      patients.

PMID- 20144382
TI  - Perioperative and critical illness dysglycemia--controlling the iceberg.
AB  - Patients with dysglycemia related to known or unrecognized diabetes, stress
      hyperglycemia, or hypoglycemia in the presence or absence of exogenous insulin
      routinely require care during the perioperative period or critical illness.
      Recent single and multicenter studies, a large multinational study, and three
      meta-analyses evaluated the safety of routine tight glycemic control (80-110
      mg/dl) in critically ill adults. Results led to a call for more modest treatment
      goals (initiation of insulin at a blood glucose >180 mg/dl with a goal of
      approximately 150 mg/dl). In this symposium, an international group of
      multidisciplinary experts discusses the role of tight glycemic control, glucose
      measurement technique and its accuracy, glucose variability, hypoglycemia, and
      innovative methods to facilitate glucose homeostasis in this heterogeneous
      patient population.

PMID- 20144383
TI  - Glycemic variability and mortality in critically ill patients: the impact of
      diabetes.
AB  - BACKGROUND: Glycemic variability (GV) has recently been associated with mortality
      in critically ill patients. The impact of diabetes or its absence on GV as a risk
      factor for mortality is unknown. METHODS: A total of 4084 adult intensive care
      unit (ICU) patients admitted between October 15, 1999, and June 30, 2009, with at
      least three central laboratory measurements of venous glucose samples during ICU
      stay were studied retrospectively. The patients were analyzed according to
      treatment era and presence or absence of diabetes: 1460 admitted before February
      1, 2003, when there was no specific treatment protocol for hyperglycemia ("PRE")
      and 2624 patients admitted after a glycemic control protocol was instituted
      ("GC"). 3142 were patients without diabetes ("NON"), and 942 were patients with
      diabetes ("DM"). The coefficient of variation (CV) [standard deviation (SD)/mean
      glucose level (MGL)] of each patient was used as a measure of GV. Patients were
      grouped by MGL (mg/dl) during ICU stay (70-99, 100-119, 120-139, 140-179, and
      180+) as well as by CV (<15%, 15-30%, 30-50%, and 50%+). RESULTS: Patients with
      diabetes had higher MGL, SD, and CV than did NON (p < .0001 for all comparisons).
      Mean glucose level was lower among both GC groups compared to their corresponding
      PRE groups (p < .0001), but CV did not change significantly between eras.
      Multivariable logistic regression analysis demonstrated that low CV was
      independently associated with decreased risk of mortality and high CV was
      independently associated with increased risk of mortality among NON PRE and GC
      patients, even after exclusion of patients with severe (<40 mg/dl) or moderate
      (40-59 mg/dl) hypoglycemia. There was no association between CV and mortality
      among DM using the same multivariable model. Mortality among NON from the entire
      cohort, with MGL 70-99 mg/dl during ICU stay, was 10.2% for patients with CV <
      15% versus 58.3% for those with CV 50%+; for NON with MGL 100-119 mg/dl,
      corresponding rates were 10.6% and 55.6%. CONCLUSIONS: Low GV during ICU stay was
      associated with increased survival among NON, and high GV was associated with
      increased mortality, even after adjustment for severity of illness. There was no
      independent association of GV with mortality among DM. Attempts to minimize GV
      may have a significant beneficial impact on outcomes of critically ill patients
      without diabetes.

PMID- 20144384
TI  - Reducing glycemic variability in intensive care unit patients: a new therapeutic
      target?
AB  - Acute hyperglycemia is common in critically ill patients. Strict control of blood
      glucose (BG) concentration has been considered important because hyperglycemia is
      associated independently with increased intensive care unit mortality. After
      intensive insulin therapy was reported to reduce mortality in selected surgical
      critically ill patients, lowering of BG levels was recommended as a means of
      improving patient outcomes. However, a large multicenter multination study has
      found that intensive insulin therapy increased mortality significantly. A
      difference in variability of BG control may be one possible explanation why the
      effect of intensive insulin therapy varied from beneficial to harmful. Several
      studies have confirmed significant associations between variability of BG levels
      and patient outcomes. Decreasing the variability of the BG concentration may be
      an important dimension of glucose management. If reducing swings in the BG
      concentration is a major biologic mechanism behind the putative benefits of
      glucose control, it may not be necessary to pursue lower glucose levels with
      their attendant risk of hypoglycemia.

PMID- 20144385
TI  - Clinical need for continuous glucose monitoring in the hospital.
AB  - Automation and standardization of the glucose measurement process have the
      potential to greatly improve glycemic control, clinical outcome, and safety while
      reducing cost. The resources required to monitor glycemia in hospitalized
      patients have thus far limited the implementation of intensive glucose management
      to patients in critical care units. Numerous available and up-and-coming
      technologies are targeted for the hospital patient population. Advantages and
      limitations of these devices are discussed herewith in.

PMID- 20144386
TI  - Glycemic control in the burn intensive care unit: focus on the role of anemia in
      glucose measurement.
AB  - Glycemic control with intensive insulin therapy (IIT) has received widespread
      adoption secondary to findings of improved clinical outcomes and survival in the
      burn population. Severe burn as a model for trauma is characterized by a
      hypermetabolic state, hyperglycemia, and insulin resistance. In this article, we
      review the findings of a burn center research facility in terms of understanding
      glucose management. The conferred benefits from IIT, our findings of poor
      outcomes associated with glycemic variability, advantages from preserved diurnal
      variation of glucose and insulin, and impacts of glucometer error and hematocrit
      correction factor are discussed. We conclude with direction for further study and
      the need for a reliable continuous glucose monitoring system. Such efforts will
      further the endeavor for achieving adequate glycemic control in order to assess
      the efficacy of target ranges and use of IIT.

PMID- 20144387
TI  - Glycemic control in the medical intensive care unit.
AB  - Hyperglycemia in the critically ill is a well-known phenomenon, even in those
      without known diabetes. The stress response is due to a complex interplay between
      counter-regulatory hormones, cytokines, and changes in insulin sensitivity.
      Illness/infection, overfeeding, medications (e.g., corticosteroids), insufficient
      insulin, and/or volume depletion can be additional contributors. Acute
      hyperglycemia can adversely affect fluid balance (through glycosuria and
      dehydration), immune and endothelial function, inflammation, and outcome. While
      there are several insulin infusion protocols that are able to safely and
      effectively treat hyperglycemia, the bulk of accumulated evidence does not
      support a causal relationship between acute hyperglycemia and adverse outcomes in
      the medical intensive care unit. Meta-analysis of randomized controlled trials
      suggests there is no benefit to tightening glucose control to normal levels
      compared to a reasonable and achievable goal of 140 to 180 mg/dl. There is a
      significantly increased risk of hypoglycemia. Although there is some evidence
      that patients without known diabetes have worse outcomes than those with known
      diabetes, more recent evidence is conflicting. Glycemic control in critically ill
      patients should not be neglected, as studies have not tested tight versus no/poor
      control, but tight versus good control. A moderate approach to managing critical
      illness hyperglycemia seems most prudent at this juncture. Future research should
      ascertain whether there are certain subgroups of patients that would benefit from
      tighter glycemic goals. It also remains to be seen if tight glucose control is
      beneficial once hypoglycemia is minimized with technological advances such as
      continuous glucose monitoring systems.

PMID- 20144388
TI  - An overview of glycemic control in the coronary care unit with recommendations
      for clinical management.
AB  - The observation that elevated glucose occurs frequently in the setting of acute
      myocardial infarction was made decades ago. Since then numerous studies have
      documented that hyperglycemia is a powerful risk factor for increased mortality
      and in-hospital complications in patients with acute coronary syndromes. While
      some questions in this field have been answered in prior investigations, many
      critical gaps in knowledge continue to exist and remain subjects of intense
      debate. This review summarizes what is known about the relationship between
      hyperglycemia, glucose control, and outcomes in critically ill patients with
      acute coronary syndromes, addresses the gaps in knowledge and controversies, and
      offers general recommendations regarding glucose management in the coronary care
      unit.

PMID- 20144389
TI  - A review of perioperative glucose control in the neurosurgical population.
AB  - Significant fluctuations in serum glucose levels accompany the stress response of
      surgery or acute injury and may be associated with vascular or neurologic
      morbidity. Maintenance of euglycemia with intensive insulin therapy (IIT)
      continues to be investigated as a therapeutic intervention to decrease morbidity
      associated with derangements in glucose metabolism. Hypoglycemia is a common side
      effect of IIT with potential for significant morbidity, especially in the
      neurologically injured patient. Differences in cerebral versus systemic glucose
      metabolism, the time course of cerebral response to injury, and heterogeneity of
      pathophysiology in neurosurgical patient populations are important to consider in
      evaluating the risks and benefits of IIT. While extremes of glucose levels are to
      be avoided, there are little data to support specific use of IIT for maintenance
      of euglycemia in the perioperative management of neurosurgical patients. Existing
      data are summarized and reviewed in this context.

PMID- 20144391
TI  - Blood glucose control in the trauma patient.
AB  - Hyperglycemia can be a significant problem in the trauma population and has been
      shown to be associated with increased morbidity and mortality. Hyperglycemia in
      the trauma patient, as in other critically ill patients, is caused by a
      hypermetabolic response to stress and seems to be an entity of its own rather
      than simply a marker. Although several early studies in a mixed intensive care
      unit population indicated that insulin protocols aimed at strict glucose control
      improved outcome, later studies did not support this and, in fact, encountered
      increased complications due to hypoglycemia. More recent studies in the trauma
      population, while supporting the correlation between hyperglycemia and increased
      mortality, seemed to indicate that protocols aimed at moderate glucose control
      improved outcome while limiting the incidence of hypoglycemic complications.

PMID- 20144390
TI  - Glycemic control and organ transplantation.
AB  - A discussion of hyperglycemia during organ transplantation is a broad topic that
      includes patients with a known history of diabetes pretransplant, those at risk
      for post-transplant diabetes, those with stress-induced hyperglycemia, those with
      hyperglycemia related to immunosuppressive therapy, and hyperglycemia in the
      deceased organ donor. In contrast to the plethora of articles and studies
      describing perioperative and critical care management of hyperglycemia in
      cardiac, trauma, and medical/surgical intensive care unit patients, relatively
      few published articles in the field of organ transplantation can be found. This
      article consists of a review of available literature in the form of publications
      and abstracts, and a preliminary report of the authors' work with liver
      transplantation and deceased organ donors.

PMID- 20144392
TI  - Development of computer-based training to enhance resident physician management
      of inpatient diabetes.
AB  - BACKGROUND: Treating hyperglycemia promotes better outcomes among inpatients.
      Knowledge deficits about management of inpatient diabetes are prevalent among
      resident physicians, which may affect the care of a substantial number of these
      patients. METHODS: A computer-based training (CBT) curriculum on inpatient
      diabetes and hyperglycemia was developed and implemented for use by resident
      physicians and focuses on several aspects of the management of inpatient diabetes
      and hyperglycemia: (1) review of importance of inpatient glucose control, (2)
      overview of institution-specific data, (3) triaging and initial admission actions
      for diabetes or hyperglycemia, (4) overview of pharmacologic management, (5)
      insulin-dosing calculations and ordering simulations, (6) review of existing
      policies and procedures, and (7) discharge planning. The curriculum was first
      provided as a series of lectures, then formatted and placed on the institutional
      intranet as a CBT program. RESULTS: Residents began using the inpatient CBT in
      September 2008. By August 2009, a total of 29 residents had participated in CBT:
      8 in family medicine, 12 in internal medicine, and 9 in general surgery. Most of
      the 29 residents confirmed that module content met stated objectives, considered
      the information valuable to their inpatient practices, and believed that the
      quality of the online modules met expectations. The majority reported that the
      modules took just the right amount of time to complete (typically 30 min each).
      CONCLUSIONS: Improvement in inpatient diabetes care requires continuous
      educational efforts. The CBT format and curriculum content were well accepted by
      the resident physicians. Ongoing assessment must determine whether resident
      practice patterns are influenced by such training.

PMID- 20144393
TI  - Display of glucose distributions by date, time of day, and day of week: new and
      improved methods.
AB  - OBJECTIVE: There is a need for improved methods for display of glucose
      distributions to facilitate comparisons by date, time of day, day of the week,
      and other variables for data obtained using self-monitoring of blood glucose
      (SMBG) and continuous glucose monitoring (CGM). METHOD: Stacked bar charts are
      utilized for multiple ranges of glucose values, e.g., very low, low, borderline
      low, target range, borderline high, high, and very high. Glucose ranges for these
      categories can be defined by the user, e.g., <40, 40-70, 71-80, 81-140, 141-180,
      181-250, and 251-400 mg/dl. Glucose distributions can be displayed by time of
      day, in relation to meals, by date, or by day of week. The graphic display can be
      generated using general purpose spreadsheet software such as Microsoft Excel or
      with special purpose software. RESULT: Stacked bar charts are extremely compact
      and effective. They facilitate comparison of multiple days, multiple time
      segments within a day, preprandial and postprandial glucose levels, days of the
      week, treatment periods, patients, and groups of patients. They are superior to
      use of pie charts in terms of compactness and in their ability to facilitate
      comparisons using multiple criteria and multiple subsets of the data. One can
      identify episodes of hypoglycemia and hyperglycemia and can display standard
      errors of estimates of percentages. Interpretation of these graphs is readily
      learned and requires minimal training. CONCLUSION: Use of stacked bar charts is
      generally superior to use of pie charts for display of glucose distributions and
      can potentially facilitate the analysis and interpretation of SMBG and CGM data.

PMID- 20144394
TI  - A semilogarithmic scale for glucose provides a balanced view of hyperglycemia and
      hypoglycemia.
AB  - OBJECTIVE: It would be desirable to improve the ability of physicians and
      patients to identify hypoglycemic episodes when viewing displays of glucose by
      date, time of day, or day of the week. RESEARCH DESIGN AND METHODS: A logarithmic
      scale is utilized for display of glucose versus date and time of day using a
      range of 40 to 400 mg/dl. Several plausible alternatives are considered for
      transformation of the glucose data. RESULT: Use of a semilogarithmic plot triples
      the percentage of the vertical axis allocated to hypoglycemia (e.g., 40-80 mg/dl)
      from 10% to 30.1% while compressing the hyperglycemic region. The log scale
      improves the symmetry of the glucose distribution. Transformations were evaluated
      corresponding to the Schlichtkrull M(100) value, the high blood glucose index/low
      blood glucose index of Kovatchev and associates, an index of glycemic control
      developed by the present author, and the GRADE score of Hill and coworkers.
      Results are similar for all four transformations. This approach is applicable
      both to self-monitoring of blood glucose (SMBG) and continuous glucose monitoring
      (CGM). Based on preliminary results, it is proposed that the log transform could
      potentially facilitate analysis of glucose patterns and may facilitate rapid and
      consistent detection and appreciation of the severity and consistency of
      hypoglycemic episodes, even in the presence of complex overlapping patterns
      commonly observed in both SMBG and CGM glucose profiles. CONCLUSION: Display of
      glucose on a logarithmic scale can potentially improve the accuracy of analysis
      and interpretation of popular methods for graphic display of glucose values.
      Device manufacturers should consider including options for semilogarithmic
      display of glucose on SMBG meters, CGM sensors, and software for retrospective
      analyses of glucose data.

PMID- 20144395
TI  - Treatment satisfaction and quality of life for an integrated continuous glucose
      monitoring/insulin pump system compared to self-monitoring plus an insulin pump.
AB  - BACKGROUND: Little is known about how the most advanced technology affects
      treatment satisfaction and health-related quality of life (HRQOL) in adults with
      diabetes. This study was designed to assess treatment satisfaction and HRQOL
      among users of an integrated real-time (RT) continuous glucose monitoring
      (CGM)/continuous subcutaneous insulin infusion (CSII) system compared with those
      using self-monitoring of blood glucose (SMBG) with CSII. METHODS: Participants
      were 311 adult respondents to an Internet survey, 162 using RT-CGM/CSII, 149
      using SMBG + CSII (median age 43 years; type 1 diabetes 94%; diabetes duration
      >15 years 61%; median insulin use 15 years). Respondents completed instruments
      assessing glucose monitoring system and insulin delivery system convenience,
      interference, burden, glucose control efficacy, cost satisfaction, overall
      satisfaction, and treatment preference, as well as quality of life (diabetes
      related worries, social burden, and psychological well-being). Real-time CGM/CSII
      users also assessed specific elements of the RT-CGM/CSII system. Group
      differences were assessed using analysis of covariance controlling for respondent
      characteristics. RESULTS: The RT-CGM/CSII group gave significantly better ratings
      than the SMBG + CSII group for their glucose monitoring system's glucose control
      efficacy, overall satisfaction, desire to switch, and willingness to recommend,
      and significantly worse ratings for interference with daily activities. The RT
      CGM/CSII group gave significantly better ratings than the SMBG + CSII group for
      their insulin delivery system's convenience and glucose control efficacy, overall
      satisfaction, desire to switch, and willingness to recommend. Real-time CGM/CSII
      users gave positive ratings of all system features. CONCLUSIONS: Users of the
      integrated RT-CGM/CSII system reported more benefits of treatment, higher
      treatment satisfaction and quality of life, and greater preference for this
      system than SMBG + CSII users.

PMID- 20144396
TI  - Plasma-generating glucose monitor accuracy demonstrated in an animal model.
AB  - INTRODUCTION: Four randomized controlled trials have compared mortality and
      morbidity of tight glycemic control versus conventional glucose for intensive
      care unit (ICU) patients. Two trials showed a positive outcome. However, one
      single-center trial and a large multicenter trial had negative results. The
      positive trials used accurate portable lab analyzers. The negative trial allowed
      the use of meters. The portable analyzer measures in filtered plasma, minimizing
      the interference effects. OptiScan Biomedical Corporation is developing a
      continuous glucose monitor using centrifuged plasma and mid-infrared spectroscopy
      for use in ICU medicine. The OptiScanner draws approximately 0.1 ml of blood
      every 15 min and creates a centrifuged plasma sample. Internal quality control
      minimizes sample preparation error. Interference adjustment using this technique
      has been presented at the Society of Critical Care Medicine in separate studies
      since 2006. METHOD: A good laboratory practice study was conducted on three
      Yorkshire pigs using a central venous catheter over 6 h while performing a
      glucose challenge. Matching Yellow Springs Instrument glucose readings were
      obtained. RESULTS: Some 95.7% of the predicted values were in the Clarke Error
      Grid A zone and 4.3% in the B zone. Of those in the B zone, all were within 3.3%
      of the A zone boundaries. The coefficient of determination (R(2)) was 0.993. The
      coefficient of variance was 5.02%. Animal necropsy and blood panels demonstrated
      safety. CONCLUSION: The OptiScanner investigational device performed safely and
      accurately in an animal model. Human studies using the device will begin soon.

PMID- 20144397
TI  - A benchtop closed-loop system controlled by a bio-inspired silicon implementation
      of the pancreatic beta cell.
AB  - The normal pancreatic beta-cell membrane depolarizes in response to increasing
      concentrations of glucose in a bursting pattern. At <7 mM (126 mg/dl), the cell
      is electrically silent. The bursting pulse width increases as glucose rises >7 mM
      (126 mg/dl) until a continuous train of bursting is seen at >25 mM (450 mg/dl). A
      bio-inspired silicon device has been developed using analogue electronics to
      implement membrane depolarization of the beta cell. The device is ultralow
      powered, miniaturized (5 x 5 mm), and produces a bursting output identical to
      that characterized in electrophysiological studies. OBJECTIVE: The goal of this
      study was to demonstrate the ability of silicon implementation of beta-cell
      electrophysiology to respond to a simulated glucose input and to drive an
      infusion pump in vitro. METHOD: The silicon device response to a current source
      was recorded at varying simulated glucose concentrations. Subsequently, the
      bursting response to a changing analyte concentration measured by an amperometric
      enzyme electrode was converted to a voltage, driving a syringe pump loaded with a
      50-ml syringe containing water. RESULTS: Bursting responses are comparable to
      those recorded in electrophysiology. Silicon beta-cell implementation bursts with
      a pulse width proportional to concentration and is able to drive an infusion
      pump. CONCLUSION: This is the first in vitro demonstration of closed loop insulin
      delivery utilizing miniaturized silicon implementation of beta-cell physiology in
      analogue electronics.

PMID- 20144398
TI  - Usability, participant acceptance, and safety of a prefilled insulin injection
      device in a 3-month observational survey in everyday clinical practice in
      Australia.
AB  - BACKGROUND: SoloSTAR (SOL; sanofi-aventis, Paris, France) is a prefilled insulin
      pen device for the injection of insulin glargine and insulin glulisine. This is
      the first Australian survey to determine its usability, participant acceptance,
      and safety in clinical practice. METHODS: A 3-month, nonrandomized,
      noncomparative, observational survey in Australia was conducted in individuals
      with diabetes. Participants were given SOL pens containing glargine, the
      instruction leaflet, and a toll-free helpline number. Training was offered to all
      participants. Safety data, including product technical complaints (PTCs), were
      gathered from ongoing feedback given by the participant or health care
      professional (HCP) and by independent interviews conducted 6-10 weeks after study
      start. RESULTS: Some 2674 people consented to take part across 93 sites (150
      HCPs), and 2029 participated in interviews. Of these, 52.6% had type 1 diabetes,
      16.3% had manual dexterity problems, and 15.5% had poor eyesight not corrected by
      glasses. At the time of interview, 96.8% of participants were still using SOL.
      None of the eight PTCs reported were due to technical defects; most were related
      to handling errors. Some 62 participants reported 77 adverse events; none were
      related to a PTC. The vast majority of participants (95.4%) were "very satisfied"
      or "satisfied" with using SOL, and 89.7% of the participants had no questions or
      concerns using SOL on a daily basis. Similar positive findings were reported by
      participants with manual or dexterity impairments. CONCLUSIONS: In this survey of
      everyday clinical practice, SOL had a good safety profile and was very well
      accepted by participants.

PMID- 20144399
TI  - An analysis of patient acceptance and safety of a prefilled insulin injection
      device.
AB  - This article summarizes and interprets the findings of Carter and colleagues in
      this issue of Journal of Diabetes Science and Technology, a study of the real
      world use of a prefilled insulin pen device. In this observational study, people
      with type 1 and type 2 diabetes rated their experience with the SoloSTAR pen
      device after 6-10 weeks of use. Data on patient satisfaction, product technical
      complaints, and adverse effects were reported. Randomized, controlled trials are
      needed that compare the various pen devices and the vial/syringe in terms of
      accuracy of dosing, adherence to therapy, and ease of use (including patient
      perception of injection force required) to assess whether a particular method of
      insulin delivery or pen delivery device provides a clinical advantage over
      another.

PMID- 20144400
TI  - Combined pioglitazone and metformin treatment maintains the beneficial effect of
      short-term insulin infusion in patients with type 2 diabetes: results from a
      pilot study.
AB  - BACKGROUND: The aim of our study was to examine the efficacy of short-term
      intravenous insulin intervention followed by oral pioglitazone/metformin therapy
      to prevent patients from continuous insulin application. METHODS: This
      prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5
      female, 9 male; age 60 +/- 2 years; body mass index 29 +/- 3.2 kg/m(2);
      hemoglobin A1c [HbA1c] 7.6 +/- 1.1%) with (1) insufficient glycemic control under
      a dose of metformin >or=1700 mg/day and/or metformin plus additional oral
      antidiabetes drugs (OADs) and (2) appropriate residual beta-cell function.
      Initially, an inpatient 34 h continuous intravenous insulin infusion was
      performed, and metformin was given (2x 850 mg/day). Insulin was stopped, and
      pioglitazone 30 mg/day was added at the second inpatient day. Patients were
      followed for four months. Efficacy parameters [change of HbA1c, fasting blood
      glucose [FBG], intact proinsulin, adiponectin, and high-sensitivity C-reactive
      protein (hsCRP)] were assessed after initial normalization of blood glucose
      values by intravenous insulin and at the study end point. RESULTS: During the
      acute insulin intervention, FBG levels were stabilized in all study subjects. In
      the following OAD treatment period, five patients showed an improvement of HbA1c
      > 0.5% [35.7%; seven patients remained stable (50.0%), two patients were
      nonresponders (14.3%)]. Fasting glucose values dropped after insulin infusion (
      17.7%; p < .001). This effect was maintained during the consecutive OAD treatment
      period (glucose +0.3%, not significant (NS); HbA1c -6.0%; p < .05). The initial
      decrease in fasting intact proinsulin levels was also maintained during the study
      (end value -41%, p < .05). Improvements in hsCRP values (postinsulin value, -15%,
      NS; end value -37%; p < .05) and adiponectin values (postinsulin value +15%, NS;
      end value +128%; p < .001) were demonstrated at end point only after continued
      glitazone intake. CONCLUSIONS: Our pilot study demonstrated that a beneficial
      effect of a short-term intravenous insulin application on glycemic control was
      effectively maintained by pioglitazone/metformin treatment for at least 4 months.
      In addition, the oral therapy significantly improved cardiovascular risk
      parameters.

PMID- 20144401
TI  - Hepatic-directed vesicle insulin: a review of formulation development and
      preclinical evaluation.
AB  - Hepatic-directed vesicle insulin (HDV-I), a novel investigational vesicle (<150
      nm diameter) insulin delivery system that carries insulin and a specific
      hepatocyte-targeting molecule (HTM) in its phospholipid bilayer and has the
      ability to mimic a portal vein insulin infusion remotely [subcutaneous (SC) HDV
      I] and noninvasively (oral HDV-I), has been developed. This review summarizes
      formulation development, subsequent refinements, and results of preclinical
      evaluation studies, including biodistribution, mechanistic, and toxicology
      studies of predominantly SC HDV-I, in various animal models. Studies conducted to
      date have confirmed the hepatocyte specificity of HDV and HDV-I and revealed that
      HDV-I can stimulate the conversion of hepatic glucose output to uptake at a dose
      that is <1% of the dose of regular insulin (RI) required for liver stimulation;
      suggest that the enhanced antihyperglycemic effect of HDV-I is due to hepatic
      glucose uptake; and in pancreatectomized dogs during an oral glucose tolerance
      test, HDV-I normalized blood glucose curves when compared to control curves in
      intact dogs and prevented secondary hypoglycemia in contrast to the same dose of
      RI. A 28-day SC HDV toxicity study in rats revealed no clinical, clinical
      laboratory, or histopathological findings, and the battery of three genetic
      toxicology studies was negative. Results support the hypothesis that HDV-I works
      by stimulating hepatic glucose uptake and/or glycogen storage in insulin
      deficient animals. The ability to target the delivery of HDV-I to the liver
      reestablishes the liver as a major metabolic modulator of glucose metabolism. The
      future of HDV-I depends on the results of ongoing development and longer term
      clinical trials.

PMID- 20144402
TI  - Health technologies for monitoring and managing diabetes: a systematic review.
AB  - BACKGROUND: The primary objective of this review was to determine the strength of
      evidence for the effectiveness of self-monitoring devices and technologies for
      individuals with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus
      (T2DM) based on specific health-related outcome measures. Self-monitoring devices
      included those that assist patients with managing diabetes and preventing
      cardiovascular complications (CVCs). A secondary objective was to explore issues
      of feasibility, usability, and compliance among patients and providers. METHODS:
      Study criteria included individuals >or=14 years and youth (7-14 years) with T1DM
      or T2DM, intervention with a self-monitoring device, assessment of clinical
      outcomes with the device, literature in English, and >or=10 participants.
      Relevant published literature was searched from 1985 to 2008. Randomized
      controlled trials and observational studies were included. Data were extracted
      for clinical outcomes, feasibility and compliance methods, and results. Selected
      studies were independently evaluated with a validated instrument for assessing
      methodological quality. RESULTS: Eighteen trials were selected. Predominant types
      of device interventions included self-monitoring of blood glucose, pedometers,
      and cell phone or wireless technologies. Feasibility and compliance were measured
      in the majority of studies. CONCLUSIONS: Self-monitoring of blood glucose
      continues to be an effective tool for the management of diabetes. Wireless
      technologies can improve diabetes self-care, and pedometers are effective
      lifestyle modification tools. The results of this review indicate a need for
      additional controlled trial research on existing and novel technologies for
      diabetes self-monitoring, on health outcomes associated with diabetes and CVCs,
      and device feasibility and compliance.

PMID- 20144403
TI  - Reducing cardiometabolic risk in peritoneal dialysis patients: role of the
      dialysis solution.
AB  - Peritoneal dialysis (PD) is a well-established form of therapy for stage 5
      chronic kidney disease requiring renal replacement therapy. D-Glucose has been
      used successfully for several decades as the osmotic agent employed in dialysis
      solutions to achieve adequate fluid removal. The absorption of 100-200 grams of
      glucose per day has been suggested as potentially increasing cardiometabolic
      risk, particularly in patients with diabetes. Supporting and undermining evidence
      for this hypothesis is reviewed, with a focus on the role of glucose absorption
      in changes in body composition, dyslipidemia, and glycemic control in diabetic PD
      patients. Clinical strategies to optimize fluid removal while minimizing the
      metabolic impact of glucose absorption are also discussed.

PMID- 20144404
TI  - Mobile phone technology for children with type 1 and type 2 diabetes: a parent
      survey.
AB  - PURPOSE: The novel application of information technology has the potential to
      improve care for children with diabetes. We surveyed parents of children with
      type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) to (1)
      identify their concerns related to their children's diabetes and (2) assess the
      relationship between these concerns and parental attitudes toward a glucometer
      integrated into a mobile phone that could provide parents and health care
      providers with a child's real-time glucose readings via text message and a secure
      Web site. METHODS: We conducted a cross-sectional Web-based survey of parents
      with children ages 10-19 years (125 with T1DM and 77 with T2DM). Parental
      concerns were grouped by (1) access to their child's provider, (2) parenting
      challenges, and (3) knowledge about managing their child's diabetes. RESULTS:
      Parental concerns focused mostly on access to their child's health care provider.
      Over half of respondents expressed interest in subscribing to a mobile-phone
      based service. In multivariate logistic regression models, the odds of being
      willing to use the service increased if parents had concerns about provider
      access, a child with T2DM, a college education, or currently subscribed to text
      messaging. Enthusiasm decreased with increasing annual service cost. CONCLUSIONS:
      Study participants-particularly parents with provider access concerns or a child
      with T2DM-were receptive to adopting novel health technology to help manage their
      children's diabetes. Adoption of such tools is most likely driven by the unmet
      needs of parents.

PMID- 20144405
TI  - Insulin pump therapy: what is the evidence for using different types of boluses
      for coverage of prandial insulin requirements?
AB  - Bolus infusion of insulin along with a meal is a standard procedure with
      continuous subcutaneous insulin infusion. Modern insulin pumps allow applying
      this bolus in four different ways: infusion of the total dose at once or
      splitting the dose into two boluses, infusion of a part of the bolus in the usual
      manner plus infusion of the other part over a prolonged period of time (with a
      higher infusion rate than the basal rate), or infusion of the total dose in the
      form of an elevated basal rate. Depending on the composition of the given meal
      and its glycemic index, this is an attempt to match the circulating insulin
      levels to the rate of glucose absorption from the gut in order to minimize
      postprandial glycemic excursions. However, in the framework of evidence-based
      medicine, the benefits of this approach should be proven in appropriately
      designed clinical studies. Performance of meal-related studies requires careful
      attention to many aspects in order to allow meaningful evaluation of a given
      intervention (i.e., type of bolus). Critical evaluation of the clinical
      experimental studies and the one clinical study published about the impact of
      different types of boluses on postprandial metabolic control revealed fundamental
      shortcomings in study design and performance in these studies. Insufficient
      establishment of comparable preprandial glycemia and insulinemia on the different
      study days within and between the patients studied is one key aspect. Therefore,
      the recommendation made in most of these studies (i.e., use of dual-wave bolus)
      has to be accepted with care, until we have better evidence.

PMID- 20144406
TI  - Enhanced 911/global position system wizard: a telemedicine application for the
      prevention of severe hypoglycemia--monitor, alert, and locate.
AB  - Intensive insulin therapy has an inherent risk of hypoglycemia that can lead to
      loss of consciousness, cardiac arrhythmia, seizure, and death ("dead-in-bed
      syndrome"). This risk of hypoglycemia is a major concern for patients, families,
      and physicians. The need for an automated system that can alert in the event of
      severe hypoglycemia is evident. In engineering systems, where there is a risk of
      malfunction of the primary control system, alert and safety mechanisms are
      implemented in layers of protection. This concept has been adopted in the
      proposed system that integrates a hypoglycemia prediction algorithm with a global
      position system (GPS) locator and short message service such that the current
      glucose value with the rate of change (ROC) and the location of the subject can
      be communicated to a predefined list. Furthermore, if the system is linked to the
      insulin pump, it can suspend the pump or decrease the basal insulin infusion rate
      to prevent the pending event. The system was evaluated on clinical datasets of
      glucose tracings from the DexCom Seven system. Glucose tracings were analyzed for
      hypoglycemia events and then a text message was broadcast to a predefined list of
      people who were notified with the glucose value, ROC, GPS coordinates, and a
      Google map of the location. In addition to providing a safety layer to a future
      artificial pancreas, this system also can be easily implemented in current
      continuous glucose monitors to help provide information and alerts to people with
      diabetes.

PMID- 20144407
TI  - Are type 2 diabetes patients who self-monitor blood glucose special? The role of
      confounders in the observational ROSSO study.
AB  - BACKGROUND: In the German multicenter, retrospective cohort study (ROSSO), those
      patients with type 2 diabetes who performed self-monitoring of blood glucose
      (SMBG) had a better long-term clinical outcome. We analyzed whether confounders
      accounted for the lower rate of clinical events in the SMBG cohort. METHODS:
      ROSSO followed 3268 persons from diagnosis of type 2 diabetes for a mean of 6.5
      years. Data were retrieved from patient files of randomly contacted primary care
      practices. RESULTS: In total, more than 60 potential confounders were documented,
      including nondisease-associated parameters such as patient's health insurance,
      marital status, habitation, and characteristics of diabetes centers. There were
      only modest differences for these parameters between groups with versus without
      SMBG, and multiple adjustments did not weaken the association of SMBG use with
      better outcome (odds ratio 0.65, 95% confidence interval 0.53-0.81, p < .001).
      This was also true for subgroups of patients defined by type of antidiabetes
      treatment. Propensity score analysis confirmed the association of SMBG use with
      outcome. Using key baseline parameters, 813 matching pairs of patients were
      identified. The analysis again showed a better long-term outcome in the SMBG
      group (hazard ratio 0.67 p = .004). CONCLUSION: An influence of nonrecognized
      confounders on better outcome in the SMBG group is rendered improbable by similar
      results obtained with adjustments for disease-associated or disease-independent
      parameters, by the analysis of patient subgroups, by propensity score analysis
      and by performing a matched-pair analysis. The higher flexibility in
      pharmacological antidiabetes treatment regimens in the SMBG cohort suggests a
      different attitude of treating physicians and patients in association with SMBG.

PMID- 20144408
TI  - Is the drugstore safe? Counterfeit diabetes products on the shelves.
AB  - It is no longer possible to identify counterfeit medical products, including
      medications and devices, by simply checking packaging and labeling. Improvements
      in technology have made it cheaper and easier to produce fake packaging and
      labels, making it nearly impossible for consumers and authorities to detect
      counterfeits without conducting tests on the products themselves, as illustrated
      by the sale of over one million counterfeit blood glucose test strips sold to
      unsuspecting U.S. consumers at drugstores in more than 35 states and in other
      countries around the world in the fall of 2006. The pricier the drugs, the more
      counterfeiters seek to mimic them to maximize returns, victimizing those patients
      at highest risk who rely on life-saving medications.

PMID- 20144409
TI  - The business of intensive insulin therapy for type 2 diabetes patients: where it
      all began for me.
AB  - Ideally, it would be easy for physicians with Diabetes Control and Complications
      Trial data in hand to convince type 2 diabetes mellitus (T2DM) patients on
      insulin to move toward intensive insulin therapy (IIT), but in actuality, patient
      compliance remains a significant issue. One of the statistics that best
      illustrates this point is that 89% of T2DM patients on insulin do not inject
      themselves outside of the home (according to the National Health and Nutrition
      Examination Survey). The market has responded to poor compliance by developing
      insulin pens and different insulin formulations to improve compliance. But the
      fact remains that most T2DM patients on insulin are out of control. I would
      suggest that, in addition to better education, an opportunity exists for a
      medical device approach to better facilitate an easy-to-use, discreet approach to
      moving from conventional to IIT.

PMID- 20144410
TI  - Medical obesity treatment: long-term success in a primary care setting.

PMID- 20144411
TI  - The missing element of telemedicine for diabetes: decision support software.

PMID- 20144412
TI  - Progress in development of an artificial pancreas.
AB  - This issue of Journal of Diabetes Science and Technology contains a collection of
      12 original articles describing the latest advances in the development of
      algorithms for controlling insulin delivery in an artificial pancreas. Algorithms
      presented in this issue are affected by numerous quantifiable factors, including
      insulin pharmaco-kinetics, timing of meal carbohydrate appearance, meal size,
      amount of exercise, presence of stress, day-to-day variations in insulin
      sensitivity, insulin time-activity profiles, accuracy of glucose monitor
      calibration, metabolic profiles of both adults and neonates, and risks of
      hypoglycemia/hyperglycemia. These articles present theoretical advances in
      insulin delivery algorithms from modeled in silico patients, as well as clinical
      data from actual patients who have used closed loop systems. The novel approaches
      described in these articles are expected to bring us much closer to realization
      of a commercially available closed loop system for controlling glucose levels in
      patients with diabetes.

PMID- 20144413
TI  - Glucose clamp algorithms and insulin time-action profiles.
AB  - MOTIVATION: Most current insulin pumps include an insulin-on-board (IOB) feature
      to help subjects avoid problems associated with "insulin stacking." In addition,
      many control algorithms proposed for a closed-loop artificial pancreas make use
      of IOB to reduce the probability of hypoglycemic events that often occur due to
      the integral action of the controller. The IOB curves are generated from the
      pharmacodynamic (time-activity profiles) actions of subcutaneous insulin, which
      are obtained from glycemic clamp studies. METHODS: Glycemic clamp algorithms are
      reviewed and in silico studies are performed to analyze the effect of glucose
      meter bias and noise on glycemic control and the manipulated glucose infusion
      rates. The glucose infusion rates are used to obtain insulin time-activity
      profiles, which are then used to generate IOB curves. RESULTS: A model-based,
      three-step-ahead controller is shown to be equivalent to a proportional-integral
      control algorithm with time-delay compensation. A systematic glucose meter bias
      of +6 mg/dl results in a decrease in the glucose area under the curve of 3% but
      no change in the IOB profiles. CONCLUSIONS: Based on these preliminary simulation
      studies, a substantial amount of glucose meter bias and noise during a glycemic
      clamp can be tolerated with little net effect on the IOB curves. It is suggested
      that handheld glucose meters can therefore be used in clamp studies if the
      measurements are filtered (averaged) before processing by the control algorithm.
      Clinical studies are needed to confirm these preliminary results.

PMID- 20144414
TI  - Closed-loop artificial pancreas using subcutaneous glucose sensing and insulin
      delivery and a model predictive control algorithm: preliminary studies in Padova
      and Montpellier.
AB  - New effort has been made to develop closed-loop glucose control, using
      subcutaneous (SC) glucose sensing and continuous subcutaneous insulin infusion
      (CSII) from a pump, and a control algorithm. An approach based on a model
      predictive control (MPC) algorithm has been utilized during closed-loop control
      in type 1 diabetes patients. Here we describe the preliminary clinical experience
      with this approach. Six type 1 diabetes patients (three in each of two clinical
      investigation centers in Padova and Montpellier), using CSII, aged 36 +/- 8 and
      48 +/- 6 years, duration of diabetes 12 +/- 8 and 29 +/- 4 years, hemoglobin A1c
      7.4% +/- 0.1% and 7.3% +/- 0.3%, body mass index 23.2 +/- 0.3 and 28.4 +/- 2.2
      kg/m(2), respectively, were studied on two occasions during 22 h overnight
      hospital admissions 2-4 weeks apart. A Freestyle Navigator(R) continuous glucose
      monitor and an OmniPod insulin pump were applied in each trial. Admission 1 used
      open-loop control, while admission 2 employed closed-loop control using our MPC
      algorithm. In Padova, two out of three subjects showed better performance with
      the closed-loop system compared to open loop. Altogether, mean overnight plasma
      glucose (PG) levels were 134 versus 111 mg/dl during open loop versus closed
      loop, respectively. The percentage of time spent at PG > 140 mg/dl was 45% versus
      12%, while postbreakfast mean PG was 165 versus 156 mg/dl during open loop versus
      closed loop, respectively. Also, in Montpellier, two patients out of three showed
      a better glucose control during closed-loop trials. Avoidance of nocturnal
      hypoglycemic excursions was a clear benefit during algorithm-guided insulin
      delivery in all cases. This preliminary set of studies demonstrates that closed
      loop control based entirely on SC glucose sensing and insulin delivery is
      feasible and can be applied to improve glucose control in patients with type 1
      diabetes, although the algorithm needs to be further improved to achieve better
      glycemic control.

PMID- 20144415
TI  - Probabilistic evolving meal detection and estimation of meal total glucose
      appearance.
AB  - BACKGROUND: Automatic compensation of meals for type 1 diabetes patients will
      require meal detection from continuous glucose monitor (CGM) readings. This is
      challenged by the uncertainty and variability inherent to the digestion process
      and glucose dynamics as well as the lag and noise associated with CGM sensors.
      Thus any estimation of meal start time, size, and shape is fundamentally
      uncertain. This uncertainty can be reduced, but not eliminated, by estimating
      total glucose appearance and using new readings as they become available. METHOD:
      In this article, we propose a probabilistic, evolving method to detect the
      presence and estimate the shape and total glucose appearance of a meal. The
      method is unique in continually evolving its estimates and simultaneously
      providing uncertainty measures to monitor their convergence. The algorithm
      operates in three phases. First, it compares the CGM signal to no-meal
      predictions made by a simple insulin-glucose model. Second, it fits the residuals
      to potential, assumed meal shapes. Finally, it compares and combines these fits
      to detect any meals and estimate the meal total glucose appearance, shape, and
      total glucose appearance uncertainty. RESULTS: We validate the performance of
      this meal detection and total glucose appearance estimation algorithm both
      separately and in cooperation with a controller on the Food and Drug
      Administration-approved University of Virginia/Padova Type I Diabetes Simulator.
      In cooperation with a controller, the algorithm reduced the mean blood glucose
      from 137 to 132 mg/dl over 1.5 days of control without any increased
      hypoglycemia. CONCLUSION: This novel, extensible meal detection and total glucose
      appearance estimation method shows the feasibility, relevance, and performance of
      evolving estimates with explicit uncertainty measures for use in closed-loop
      control of type 1 diabetes.

PMID- 20144416
TI  - Closed-loop artificial pancreas using subcutaneous glucose sensing and insulin
      delivery and a model predictive control algorithm: the Virginia experience.
AB  - BACKGROUND: Recent progress in the development of clinically accurate continuous
      glucose monitors (CGMs), automated continuous insulin infusion pumps, and control
      algorithms for calculating insulin doses from CGM data have enabled the
      development of prototypes of subcutaneous closed-loop systems for controlling
      blood glucose (BG) levels in type 1 diabetes. The use of a new personalized model
      predictive control (MPC) algorithm to determine insulin doses to achieve and
      maintain BG levels between 70 and 140 mg/dl overnight and to control postprandial
      BG levels is presented. METHODS: Eight adults with type 1 diabetes were studied
      twice, once using their personal open-loop systems to control BG overnight and
      for 4 h following a standardized meal and once using a closed-loop system that
      utilizes the MPC algorithm to control BG overnight and for 4 h following a
      standardized meal. Average BG levels, percentage of time within BG target of 70
      140 mg/dl, number of hypoglycemia episodes, and postprandial BG excursions during
      both study periods were compared. RESULTS: With closed-loop control, once BG
      levels achieved the target range (70-140 mg/dl), they remained within that range
      throughout the night in seven of the eight subjects. One subject developed a BG
      level of 65 mg/dl, which was signaled by the CGM trend analysis, and the MPC
      algorithm directed the discontinuance of the insulin infusion. The number of
      overnight hypoglycemic events was significantly reduced (p = .011) with closed
      loop control. Postprandial BG excursions were similar during closed-loop and open
      loop control. CONCLUSION: Model predictive closed-loop control of BG levels can
      be achieved overnight and following a standardized breakfast meal. This
      "artificial pancreas" controls BG levels as effectively as patient-directed open
      loop control following a morning meal but is significantly superior to open-loop
      control in preventing overnight hypoglycemia.

PMID- 20144417
TI  - Automatic data processing to achieve a safe telemedical artificial pancreas.
AB  - BACKGROUND: The use of telemedicine for diabetes care has evolved over time,
      proving that it contributes to patient self-monitoring, improves glycemic
      control, and provides analysis tools for decision support. The timely development
      of a safe and robust ambulatory artificial pancreas should rely on a telemedicine
      architecture complemented with automatic data analysis tools able to manage all
      the possible high-risk situations and to guarantee the patient's safety. METHODS:
      The Intelligent Control Assistant system (INCA) telemedical artificial pancreas
      architecture is based on a mobile personal assistant integrated into a
      telemedicine system. The INCA supports four control strategies and implements an
      automatic data processing system for risk management (ADP-RM) providing short
      term and medium-term risk analyses. The system validation comprises data from 10
      type 1 pump-treated diabetic patients who participated in two randomized
      crossover studies, and it also includes in silico simulation and retrospective
      data analysis. RESULTS: The ADP-RM short-term risk analysis prevents hypoglycemic
      events by interrupting insulin infusion. The pump interruption has been
      implemented in silico and tested for a closed-loop simulation over 30 hours. For
      medium-term risk management, analysis of capillary blood glucose notified the
      physician with a total of 62 alarms during a clinical experiment (56% for
      hyperglycemic events). The ADP-RM system is able to filter anomalous continuous
      glucose records and to detect abnormal administration of insulin doses with the
      pump. CONCLUSIONS: Automatic data analysis procedures have been tested as an
      essential tool to achieve a safe ambulatory telemedical artificial pancreas,
      showing their ability to manage short-term and medium-term risk situations.

PMID- 20144419
TI  - Control to range for diabetes: functionality and modular architecture.
AB  - BACKGROUND: Closed-loop control of type 1 diabetes is receiving increasing
      attention due to advancement in glucose sensor and insulin pump technology. Here
      the function and structure of a class of control algorithms designed to exert
      control to range, defined as insulin treatment optimizing glycemia within a
      predefined target range by preventing extreme glucose fluctuations, are studied.
      METHODS: The main contribution of the article is definition of a modular
      architecture for control to range. Emphasis is on system specifications rather
      than algorithmic realization. The key system architecture elements are two
      interacting modules: range correction module, which assesses the risk for
      incipient hyper- or hypoglycemia and adjusts insulin rate accordingly, and safety
      supervision module, which assesses the risk for hypoglycemia and attenuates or
      discontinues insulin delivery when necessary. The novel engineering concept of
      range correction module is that algorithm action is relative to a nominal open
      loop strategy-a predefined combination of basal rate and boluses believed to be
      optimal under nominal conditions. RESULTS: A proof of concept of the feasibility
      of our control-to-range strategy is illustrated by using a prototypal
      implementation tested in silico on patient use cases. These functional and
      architectural distinctions provide several advantages, including (i) significant
      insulin delivery corrections are only made if relevant risks are detected; (ii)
      drawbacks of integral action are avoided, e.g., undershoots with consequent
      hypoglycemic risks; (iii) a simple linear model is sufficient and complex
      algorithmic constraints are replaced by safety supervision; and (iv) the nominal
      profile provides straightforward individualization for each patient. CONCLUSIONS:
      We believe that the modular control-to-range system is the best approach to
      incremental development, regulatory approval, industrial deployment, and clinical
      acceptance of closed-loop control for diabetes.

PMID- 20144418
TI  - Identification of intraday metabolic profiles during closed-loop glucose control
      in individuals with type 1 diabetes.
AB  - BACKGROUND: Algorithms for closed-loop insulin delivery can be designed and tuned
      empirically; however, a metabolic model that is predictive of clinical study
      results can potentially accelerate the process. METHODS: Using data from a
      previously conducted closed-loop insulin delivery study, existing models of meal
      carbohydrate appearance, insulin pharmacokinetics, and the effect on glucose
      metabolism were identified for each of the 10 subjects studied. Insulin's effects
      to increase glucose uptake and decrease endogenous glucose production were
      described by the Bergman minimal model, and compartmental models were used to
      describe the pharmacokinetics of subcutaneous insulin absorption and glucose
      appearance following meals. The composite model, comprised of only five equations
      and eight parameters, was identified with and without intraday variance in
      insulin sensitivity (S(I)), glucose effectiveness at zero insulin (GEZI), and
      endogenous glucose production (EGP) at zero insulin. RESULTS: Substantial
      intraday variation in SI, GEZI and EGP was observed in 7 of 10 subjects (root
      mean square error in model fit greater than 25 mg/dl with fixed parameters and
      nadir and/or peak glucose levels differing more than 25 mg/dl from model
      predictions). With intraday variation in these three parameters, plasma glucose
      and insulin were well fit by the model (R(2) = 0.933 +/- 0.00971 [mean +/-
      standard error of the mean] ranging from 0.879-0.974 for glucose; R(2) = 0.879 +/
      0.0151, range 0.819-0.972 for insulin). Once subject parameters were identified,
      the original study could be reconstructed using only the initial glucose value
      and basal insulin rate at the time closed loop was initiated together with meal
      carbohydrate information (glucose, R(2) = 0.900 +/- 0.015; insulin delivery, R(2)
      = 0.640 +/- 0.034; and insulin concentration, R(2) = 0.717 +/- 0.041).
      CONCLUSION: Metabolic models used in developing and comparing closed-loop insulin
      delivery algorithms will need to explicitly describe intraday variation in
      metabolic parameters, but the model itself need not be comprised by a large
      number of compartments or differential equations.

PMID- 20144420
TI  - Blood glucose controller for neonatal intensive care: virtual trials development
      and first clinical trials.
AB  - BACKGROUND: Premature neonates often experience hyperglycemia, which has been
      linked to worsened outcomes. Insulin therapy can assist in controlling blood
      glucose (BG) levels. However, a reliable, robust control protocol is required to
      avoid hypoglycemia and to ensure that clinically important nutrition goals are
      met. METHODS: This study presents an adaptive, model-based predictive controller
      designed to incorporate the unique metabolic state of the neonate. Controller
      performance was tested and refined in virtual trials on a 25-patient
      retrospective cohort. The effects of measurement frequency and BG sensor error
      were evaluated. A stochastic model of insulin sensitivity was used in control to
      provide a guaranteed maximum 4% risk of BG < 72 mg/dl to protect against
      hypoglycemia as well as account for patient variability over 1-3 h intervals when
      determining the intervention. The resulting controller is demonstrated in two 24
      h clinical neonatal pilot trials at Christchurch Women's Hospital. RESULTS: Time
      in the 72-126 mg/dl BG band was increased by 103-161% compared to retrospective
      clinical control for virtual trials of the controller, with fewer hypoglycemic
      measurements. Controllers were robust to BG sensor errors. The model-based
      controller maintained glycemia to a tight target control range and accounted for
      interpatient variability in patient glycemic response despite using more insulin
      than the retrospective case, illustrating a further measure of controller
      robustness. Pilot clinical trials demonstrated initial safety and efficacy of the
      control method. CONCLUSIONS: A controller was developed that made optimum use of
      the very limited available BG measurements in the neonatal intensive care unit
      and provided robustness against BG sensor error and longer BG measurement
      intervals. It used more insulin than typical sliding scale approaches or
      retrospective hospital control. The potential advantages of a model-based
      approach demonstrated in simulation were applied to initial clinical trials.

PMID- 20144421
TI  - A closed-loop artificial pancreas using model predictive control and a sliding
      meal size estimator.
AB  - The objective of this article is to present a comprehensive strategy for a closed
      loop artificial pancreas. A meal detection and meal size estimation algorithm is
      developed for situations in which the subject forgets to provide a meal insulin
      bolus. A pharmacodynamic model of insulin action is used to provide insulin-on
      board constraints to explicitly include the future effect of past and currently
      delivered insulin boluses. In addition, a supervisory pump shut-off feature is
      presented to avoid hypoglycemia. All of these components are used in conjunction
      with a feedback control algorithm using model predictive control (MPC). A model
      for MPC is developed based on a study of 20 subjects and is tested in a
      hypothetical clinical trial of 100 adolescent and 100 adult subjects using a Food
      and Drug Administration-approved diabetic subject simulator. In addition, a
      performance comparison of previously and newly proposed meal size estimation
      algorithms using 200 in silico subjects is presented. Using the new meal size
      estimation algorithm, the integrated artificial pancreas system yielded a daily
      mean glucose of 138 and 132 mg/dl for adolescents and adults, respectively, which
      is a substantial improvement over the MPC-only case, which yielded 159 and 145
      mg/dl.

PMID- 20144422
TI  - Run-to-run tuning of model predictive control for type 1 diabetes subjects: in
      silico trial.
AB  - BACKGROUND: The technological advancements in subcutaneous continuous glucose
      monitoring and insulin pump delivery systems have paved the way to clinical
      testing of artificial pancreas devices. The experience derived by clinical trials
      poses technological challenges to the automatic control expert, the most notable
      being the large interpatient and intrapatient variability and the inherent
      uncertainty of patient information. METHODS: A new model predictive control (MPC)
      glucose control system is proposed. The starting point is an MPC algorithm
      applied in 20 type 1 diabetes mellitus (T1DM) subjects. Three main changes are
      introduced: individualization of the ARX model used for prediction; synthesis of
      the MPC law on top of the open-loop basal/bolus therapy; and a run-to-run
      approach for implementing day-by-day tuning of the algorithm. In order to
      individualize the ARX model, a sufficiently exciting insulin profile is imposed
      by splitting the premeal bolus into two smaller boluses (40% and 60%) injected 30
      min before and 30 min after the meal. RESULTS: The proposed algorithm was tested
      on 100 virtual subjects extracted from an in silico T1DM population. The trial
      simulates 44 consecutive days, during which the patient receives breakfast,
      lunch, and dinner each day. For 10 days, meals are multiplied by a random
      variable uniformly distributed in [0.5, 1.5], while insulin delivery is based on
      nominal meals. Moreover, for 10 days, either a linear increase or decrease of
      insulin sensitivity (+/-25% of nominal value) is introduced. CONCLUSIONS: The ARX
      model identification procedure offers an automatic tool for patient model
      individualization. The run-to-run approach is an effective way to auto-tune the
      aggressiveness of the closed-loop control law, is robust to meal variation, and
      is also capable of adapting the regulator to slow parameter variations, e.g., on
      insulin sensitivity.

PMID- 20144423
TI  - A novel adaptive basal therapy based on the value and rate of change of blood
      glucose.
AB  - BACKGROUND: Modern insulin pump therapy for type 1 diabetes mellitus offers the
      freedom to program several basal profiles that may accommodate diurnal ariability
      in insulin sensitivity and activity level. However, these basal profiles do not
      change even if a pending hypoglycemic or hyperglycemic event is foreseen. New
      insulin pumps could receive a direct feed of glucose values from a continuous
      glucose monitoring (CGM) system and could enable dynamic basal adaptation to
      improve glycemic control. METHOD: The proposed method is a two-step procedure.
      After the design of an initial basal profile, an adaptation of the basal rate is
      suggested as a gain multiplier based on the current CGM glucose value and its
      rate of change (ROC). Taking the glucose value and its ROC as axes, a two
      dimensional plane is divided into a nine-zone mosaic, where each zone is given a
      predefined basal multiplier; for example, a basal multiplier of zero indicates a
      recommendation to shut off the pump. RESULTS: The proposed therapy was evaluated
      on 20 in silico subjects (ten adults and ten adolescents) in the Food and Drug
      Administration-approved UVa/Padova simulator. Compared with conventional basal
      therapy, the proposed basal adjustment improved the percentage of glucose levels
      that stayed in the range of 60-180 mg/dl for all 20 subjects. In addition, the
      adaptive basal therapy reduced the average blood glucose index values.
      CONCLUSIONS: The proposed therapy provides the flexibility to account for insulin
      sensitivity variations that may result from stress and/or physical activities.
      Because of its simplicity, the proposed method could be embedded in a chip in a
      future artificial pancreatic beta cell or used in a "smart" insulin pump.

PMID- 20144424
TI  - Overnight closed-loop insulin delivery with model predictive control: assessment
      of hypoglycemia and hyperglycemia risk using simulation studies.
AB  - BACKGROUND: Hypoglycemia and hyperglycemia during closed-loop insulin delivery
      based on subcutaneous (SC) glucose sensing may arise due to (1) overdosing and
      underdosing of insulin by control algorithm and (2) difference between plasma
      glucose (PG) and sensor glucose, which may be transient (kinetics origin and
      sensor artifacts) or persistent (calibration error [CE]). Using in silico
      testing, we assessed hypoglycemia and hyperglycemia incidence during over-night
      closed loop. Additionally, a comparison was made against incidence observed
      experimentally during open-loop single-night in-clinic studies in young people
      with type 1 diabetes mellitus (T1DM) treated by continuous SC insulin infusion.
      METHODS: Simulation environment comprising 18 virtual subjects with T1DM was used
      to simulate overnight closed-loop study with a model predictive control (MPC)
      algorithm. A 15 h experiment started at 17:00 and ended at 08:00 the next day.
      Closed loop commenced at 21:00 and continued for 11 h. At 18:00, protocol
      included meal (50 g carbohydrates) accompanied by prandial insulin. The MPC
      algorithm advised on insulin infusion every 15 min. Sensor glucose was obtained
      by combining model-calculated noise-free interstitial glucose with experimentally
      derived transient and persistent sensor artifacts associated with FreeStyle
      Navigator (FSN). Transient artifacts were obtained from FSN sensor pairs worn by
      58 subjects with T1DM over 194 nighttime periods. Persistent difference due to
      FSN CE was quantified from 585 FSN sensor insertions, yielding 1421 calibration
      sessions from 248 subjects with diabetes. RESULTS: Episodes of severe (PG < or =
      36 mg/dl) and significant (PG < or = 45 mg/dl) hypoglycemia and significant
      hyperglycemia (PG > or = 300 mg/dl) were extracted from 18,000 simulated closed
      loop nights. Severe hypoglycemia was not observed when FSN CE was less than 45%.
      Hypoglycemia and hyperglycemia incidence during open loop was assessed from 21
      overnight studies in 17 young subjects with T1DM (8 males; 13.5 +/- 3.6 years of
      age; body mass index 21.0 +/- 4.0 kg/m2; duration diabetes 6.4 +/- 4.1 years;
      hemoglobin A1c 8.5% +/- 1.8%; mean +/- standard deviation) participating in the
      Artificial Pancreas Project at Cambridge. Severe and significant hypoglycemia
      during simulated closed loop occurred 0.75 and 17.11 times per 100 person years
      compared to 1739 and 3479 times per 100 person years during experimental open
      loop, respectively. Significant hyperglycemia during closed loop and open loop
      occurred 75 and 15,654 times per 100 person years, respectively. CONCLUSIONS: The
      incidence of severe and significant hypoglycemia reduced 2300- and 200-fold,
      respectively, during stimulated overnight closed loop with MPC compared to that
      observed during open-loop overnight clinical studies in young subjects with T1DM.
      Hyperglycemia was 200 times less likely. Overnight closed loop with the FSN and
      the MPC algorithm is expected to reduce substantially the risk of hypoglycemia
      and hyperglycemia.

PMID- 20144425
TI  - New approaches to display of self-monitoring of blood glucose data.
AB  - BACKGROUND: There is a need for improved methods for display and analysis of self
      monitoring of blood glucose (SMBG) data to facilitate identification of clinical
      problems, assist the clinician in the interpretation of daily patterns and
      longitudinal trends, serve as a guide to locating the most important segments of
      logbook data, and permit rapid analysis of the patient's pattern of glucose
      monitoring. METHODS: We developed prototype software to display SMBG data in a
      two-dimensional color-coded array: Time of day is displayed on the horizontal
      axis; date or sequential day is displayed on the vertical axis. Each glucose
      value is shown by a color-coded symbol categorizing it as "very high," "high,"
      "within target range," "low," or "very low." The number of categories and their
      ranges can be defined by the user, and different target ranges and limits for the
      categories can be used for different times of day. Placing the cursor over any
      observation activates a "pop-up box" showing the date, day of week, time of day,
      glucose value, and ancillary information. Several options and variations are
      available. RESULTS: This new type of display is compact, serves as a guide to
      assist the physician in locating the most important segments of the logbook, and
      permits display of glucose data from 90 or more days in a chart as small as 4 by
      4 inches. This analysis permits rapid identification of measurements that are
      above or below the target range and facilitates rapid evaluation of patterns
      observed on different days or days of the week. CONCLUSION: These new approaches
      complement other popular graphical displays by conveying information efficiently
      and effectively to the physician, other health care providers, the patient, and
      family caregivers in a new and novel, concise, standardized yet flexible format.

PMID- 20144426
TI  - Clinically significant disagreement between mean blood glucose and estimated
      average glucose in two populations: implications for diabetes management.
AB  - BACKGROUND: Hemoglobin A1c (HbA1c) is highly correlated with mean blood glucose
      (MBG) levels and widely used in assessment of diabetes therapy. It has been
      proposed to report HbA1c in terms of an estimated average glucose (eAG) derived
      from the population regression of MBG on HbA1c. Pertinent to the clinical utility
      of eAG would be the degree of agreement between eAG and MBG estimated from
      multiple sampled glucose measurements over time. METHODS: We examined agreement
      between eAG and MBG by Bland-Altman analysis from two different populations of
      type 1 diabetes patients: 150 children at our clinic in New Orleans and publicly
      available data from 1440 participants in the Diabetes Control and Complications
      Trial (DCCT). In New Orleans, MBG was derived from the mean of each patient's
      self-monitored glucose records over the 3 months before the HbA1c was obtained at
      the patient's clinic visit. Hemoglobin A1c was traceable to the DCCT. In DCCT
      participants, MBG was calculated from the patient's seven-sample glucose profile
      set submitted during each quarterly visit. Estimated average glucose was
      calculated from each individual's HbA1c using a previously reported regression
      equation of MBG versus HbA1c, eAG = (HbA1c * 28.7) - 47.7, derived from a
      continuous glucose monitoring protocol over a 12-week period. RESULTS: The
      analysis showed that there is frequent and clinically significant disagreement
      between MBG and eAG. Estimated average glucose over or under estimated MBG by
      28.7 mg/dl or greater (HbA1c difference of 1% or greater) in approximately 33% of
      patients from both populations. The eAG overestimation of MBG was highest at
      lower MBG. The difference between eAG and MBG was skewed upward with increasing
      mean of eAG and MBG in the DCCT. CONCLUSIONS: Frequent discordance between eAG
      and MBG in clinical practice will likely be confusing to patients and clinicians.
      In patients where eAG overestimates MBG, intensive management based on eAG alone
      will likely lead to greater frequency of hypoglycemic episodes. To overcome these
      limitations of eAG, a customized assessment of HbA1c with respect to a patient's
      MBG should be performed using directly monitored patient glucose levels over
      time.

PMID- 20144427
TI  - Comparison of lancing devices for self-monitoring of blood glucose regarding
      lancing pain.
AB  - BACKGROUND: Self-monitoring of blood glucose empowers diabetes patients to
      effectively control their blood glucose (BG) levels. A potential barrier to
      frequent BG controls is lancing pain, intrinsically linked to pricking the finger
      several times a day. In this study, we compared different state-of-the-art
      lancing devices from leading manufacturers regarding lancing pain, and we
      intended to identify lancing devices that are less painful. METHODS: First, 165
      subjects compared 6 different BG monitoring systems-consisting of a lancing
      device and a BG meter-at home for 36 days and at least 3 BG tests per day.
      Second, the subjects directly compared 6 different lancing devices-independent
      from a BG meter-in a laboratory setting. The test results were collected in
      questionnaires, and lancing pain was rated on a numerical rating scale. RESULTS:
      One hundred fifty-seven subjects were included in the analysis. Accu-Chek BG
      monitoring systems were significantly (p < or = .006) preferred to competitor BG
      monitoring systems and were rated by >50% of the subjects as "less painful" than
      competitor BG monitoring systems. Accu-Chek lancing devices were significantly (p
      < .001) preferred to competitor lancing devices and were rated by >60% of the
      subjects as "less painful" than competitor lancing devices. CONCLUSIONS: We found
      significant differences in lancing pain between lancing devices. Diabetes
      patients clearly preferred lancing devices that cause less lancing pain. In order
      to improve patient compliance with respect to an adequate glycemic control, the
      medical staff should preferentially prescribe lancing devices that cause less
      lancing pain.

PMID- 20144428
TI  - Analysis of the comparison of lancing devices for self-monitoring of blood
      glucose regarding lancing pain.
AB  - Reducing barriers to self-monitoring of blood glucose (SMBG) remains an ongoing
      goal. One major reported barrier is lancing pain. This analysis was written in
      response to the article by Kocher and associates in this issue of Journal of
      Diabetes Science and Technology in which 157 patients with diabetes experienced
      in the use of SMBG compared high market share blood glucose monitoring systems
      and lancing devices. Upon review of their findings, we found that their
      conclusions-Accu-check systems and lancing devices were preferred-were valid
      within the limitations of the study. However, we noted some factors that would
      warrant further study and possibly change the outcome. Information from this and
      other studies on the topic will be useful as a reference for patients and
      providers in working towards removing barriers to SMBG.

PMID- 20144429
TI  - Accuracy of the SEVEN continuous glucose monitoring system: comparison with
      frequently sampled venous glucose measurements.
AB  - BACKGROUND: The purpose of this study was to compare the accuracy of measurements
      obtained from the DexCom SEVEN system with Yellow Springs Instrument (YSI)
      laboratory measurements of venous blood glucose. METHODS: Seventy-two subjects
      with insulin-requiring diabetes, aged 18-71, were enrolled in a multicenter,
      prospective single-arm study. All participants wore the SEVEN continuous glucose
      monitoring (CGM) system for one, 7-day wear period. Calibration with capillary
      finger stick measurements was performed 2 hours after sensor insertion and once
      every 12 hours thereafter. A subset of subjects (28) wore two systems
      simultaneously to assess precision. All subjects participated in one, 10-hour in
      clinic session on day 1, 4, or 7 of the study to compare CGM measurements against
      a laboratory method (YSI analyzer) using venous measurements taken once every 20
      minutes. Carbohydrate consumption and insulin dosing were adjusted in order to
      obtain a broad range of glucose values. RESULTS: Comparison of CGM measurements
      with the laboratory reference method (n = 2318) gave mean and median absolute
      relative differences (ARDs) of 16.7 and 13.2%, respectively. The percentage was
      70.4% in the clinically accurate Clarke error grid A zone and 27.5% in the benign
      error B zone. Performance of the SEVEN system was consistent over time with mean
      and median ARD lowest on day 7 as compared to YSI (13.3 and 10.2%, respectively).
      Average sensor time lag was 5 minutes. CONCLUSIONS: Measurements of the DexCom
      SEVEN system were found to be consistent and accurate compared with venous
      measurements made using a laboratory reference method over 7 days of wear.

PMID- 20144430
TI  - An analysis of the SEVEN system: have we reached the summit of needle-type sensor
      accuracy?
AB  - In this issue of Journal of Diabetes Science and Technology, Zisser and
      colleagues show improved sensor accuracy with the newest generation of needle
      type sensors as compared to first generation sensors. Can we expect further
      improvement? It is unknown what the future holds, but there certainly seems much
      to be gained from improved calibration procedures. In addition, sensor operating
      times are increasing and it is hoped that this will translate into improved
      sensor use and thereby into improved glycemic control.

PMID- 20144431
TI  - Performance analysis of the OneTouch UltraVue blood glucose monitoring system.
AB  - BACKGROUND: OneTouch UltraVue is a new meter for self-monitoring of blood glucose
      that includes a color display, used-strip ejector, and no-button interface. The
      system uses an electrochemical biosensor technology based on glucose oxidase
      chemistry to detect glucose concentrations from 20 to 600 mg/dl (1.1 to 33.3
      mmol/liter). METHODS: Accuracy and reproducibility were evaluated over a wide
      range of glucose concentrations according to standard criteria. Clinical accuracy
      was assessed by health care providers (HCPs) in two studies and by diabetes
      patients in the second study. Reference glucose levels were determined by a YSI
      2300 analyzer. Same-day reproducibility and day-to-day reproducibility were also
      evaluated. RESULTS: In the accuracy studies, 99.7% and 98.7% of tests by HCPs and
      97.0% of tests by patients were within +/-15 mg/dl (+/-0.8 mmol/liter) of the YSI
      reference for blood glucose <75 mg/dl (<4.2 mmol/liter), and within +/-20% for
      blood glucose > or =75 mg/dl (> or =4.2 mmol/liter), respectively. Consensus
      error grid analysis showed that 99.7% and 95.3% of tests by HCPs and 97.0% of
      tests by patients fell within zone A (i.e., has no effect on clinical action);
      all other results were in zone B (i.e., altered clinical action, little or no
      effect on clinical outcome). In the reproducibility studies, the standard
      deviation was <1.5 mg/dl (<0.1 mmol/liter) for glucose concentrations <100 mg/dl
      (<5.6 mmol/liter), and the coefficient of variation was <2% for concentrations >
      or = 100 mg/dl (> or =5.6 mmol/liter). CONCLUSIONS: OneTouch UltraVue meets
      standard acceptability criteria for accuracy and reproducibility across a wide
      range of glucose concentrations. Its simple interface and lack of contact with
      used strips make it a viable option for older patients and their caregivers.

PMID- 20144432
TI  - Analysis article on the performance analysis of the OneTouch UltraVue blood
      glucose monitoring system.
AB  - In this issue of Journal of Diabetes Science and Technology, Chang and colleagues
      present the analytical performance evaluation of the OneTouch UltraVue blood
      glucose meter. This device is an advanced construction with a color display, used
      strip ejector, no-button interface, and short assay time. Accuracy studies were
      performed using a YSI 2300 analyzer, considered the reference. Altogether, 349
      pairs of results covering a wide range of blood glucose concentrations were
      analyzed. Patients with diabetes performed a significant part of the tests.
      Obtained results indicate good accuracy of OneTouch UltraVue blood glucose
      monitoring system, satisfying the International Organization for Standardization
      recommendations and thereby locating >95% of tests within zone A of the error
      grid. Results of the precision studies indicate good reproducibility of
      measurements. In conclusion, the evaluation of the OneTouch UltraVue meter
      revealed good analytical performance together with convenient handling useful for
      self-monitoring of blood glucose performed by elderly diabetes patients.

PMID- 20144433
TI  - Institutional blood glucose monitoring system for hospitalized patients: an
      integral component of the inpatient glucose control program.
AB  - BACKGROUND: The ability to measure patient blood glucose levels at bedside in
      hospitalized patients and to transmit those values to a central database enables
      and facilitates glucose control and follow-up and is an integral component in the
      care of the hospitalized diabetic patient. OBJECTIVE: The goal of this study was
      to evaluate the performance of an institutional glucometer employed in the
      framework of the Program for the Treatment of the Hospitalized Diabetic Patient
      (PTHDP) at E. Wolfson Medical Center, Holon, Israel. METHODS: As part of the
      program to facilitate glucose control in hospitalized diabetic patients, an
      institutional glucometer was employed that permits uploading of data from stands
      located in each inpatient department and downloading of that data to a central
      hospital-wide database. Blood glucose values from hospitalized diabetic patients
      were collected from August 2007 to October 2008. The inpatient glucose control
      program was introduced gradually beginning January 2008. RESULTS: During the
      follow-up period, more than 150,000 blood glucose measures were taken. Mean
      glucose was 195.7 +/- 99.12 mg/dl during the follow-up period. Blood glucose
      values declined from 206 +/- 105 prior to PTHDP (August 2007-December 2007) to
      186 +/- 92 after its inception (January 2008-October 2008). The decline was
      associated significantly with time (r = 0.11, p < 0.0001). The prevalence of
      blood glucose values lower than 60 mg/dl was 1.48% [95% confidence interval (CI)
      0.36%] prior to vs 1.55% (95% CI 0.37%) following implementation of the PTHDP.
      Concomitantly, a significant increase in the proportion of blood glucose values
      between 80 and 200 mg/dl was observed, from 55.5% prior to program initiation vs
      61.6% after program initiation (p < 0.0001). CONCLUSIONS: The present study was
      designed to observe changes in institution-wide glucose values following
      implementation of the PTHDP. Information was extracted from the glucometer system
      itself. Because the aforementioned study was not a clinical trial, we cannot rule
      out that factors other than introduction of the program could explain some of the
      variability observed. With these limitations in mind, it nevertheless appears
      that the PTHDP, of which the institutional glucometer is an integral, essential
      component, was associated with improved blood glucose values in the hospitalized
      diabetic patient.

PMID- 20144434
TI  - Inspiratory efforts achieved in use of the Technosphere insulin inhalation
      system.
AB  - OBJECTIVE: The Technosphere Insulin (TI) inhalation system comprises TI powder
      premetered into unit dose cartridges and the patient-friendly, reusable, breath
      powered MedTone inhaler. This high-resistance system uses a patient's inspiratory
      effort to effect TI powder de-agglomeration and promote subsequent deep-lung
      delivery. This study reports on flow and pressure data achieved by patients with
      diabetes using the MedTone system. METHOD: MedTone inhalers containing empty
      cartridges were adapted with pneumotach measuring devices to capture inhalation
      profiles. The measuring apparatuses had negligible impact on the nominal MedTone
      system resistance level of 0.117 kPa(0.5)/liters/min. Each of 56 subjects inhaled
      twice to mimic TI clinical study dosing instructions. Achieved inhalation
      profiles were characterized by peak inspiratory flow (PIF), peak inspiratory
      pressure (PIP), and average pressure drop from the time of PIP to 4 s (P(avg)).
      RESULTS: The achieved mean PIF (+/- standard deviation [SD]) in all subjects was
      26.74 (+/-6.06) liters/min after the first inhalation and was similar to the mean
      PIF of 26.25 (+/-6.23) liters/min achieved after the second inhalation. Mean PIP
      (+/-SD) achieved by subjects was 8.49 (+/-2.86) and 8.1 (+/-2.99) kPa, and mean
      P(avg) drop (+/-SD) in all subjects was 6.53 (+/-2.24) and 6.09 (+/-2.08) kPa
      after the respective inhalations. CONCLUSION: Patients with diabetes demonstrated
      consistent inhalation efforts over two inhalations using the MedTone system. The
      achieved PIFs and PIPs demonstrate the capacity of this population to obtain
      sufficient inspiratory effort necessary for delivery of TI using the MedTone
      inhaler. Adequate postpeak pressures were also revealed, further supporting
      reliable and sustained inhalation efforts.

PMID- 20144435
TI  - Serum insulin aspart concentrations following high-dose insulin aspart
      administered directly into the duodenum of healthy subjects: an open-labeled,
      single-blinded, and uncontrolled exploratory trial.
AB  - OBJECTIVE: The goal of this study was to determine the bioavailability of high
      dose insulin aspart administered directly into the duodenum of healthy subjects.
      METHODS: In a pilot study, four subjects each received four escalating doses of a
      1-ml solution of insulin aspart (100, 300, 600, and 1000 IU, respectively)
      directly into the duodenum. In the following main study, eight subjects each
      received two identical doses of insulin aspart of 1000 IU, in 4- and 8-ml
      solutions, respectively, directly into the duodenum. Subjects in the main study
      also received an intravenous and a subcutaneous injection of 4 to 6 IU of insulin
      aspart. RESULTS: A considerable number of samples and, in some cases, consecutive
      samples revealed significantly increased concentrations of serum insulin aspart.
      Despite the significant serum insulin aspart concentrations, no significant
      changes of plasma glucose were measured. Moreover, no significant suppression of
      endogenous insulin secretion was detected, as assessed by the levels of serum
      human insulin. CONCLUSIONS: Administration of high-dose insulin aspart directly
      into the duodenum of healthy subjects resulted in significantly increased serum
      insulin aspart concentrations in a high number of consecutive samples using a
      specific enzyme-linked immunosorbent assay. However, no significant changes in
      the levels of plasma glucose or serum human insulin were observed. Thus, the
      study did not provide any evidence of biological activity of the original insulin
      aspart molecule after high-dose administration directly into the duodenum.

PMID- 20144436
TI  - Experimental evaluation of a recursive model identification technique for type 1
      diabetes.
AB  - BACKGROUND: A model-based controller for an artificial beta cell requires an
      accurate model of the glucose-insulin dynamics in type 1 diabetes subjects. To
      ensure the robustness of the controller for changing conditions (e.g., changes in
      insulin sensitivity due to illnesses, changes in exercise habits, or changes in
      stress levels), the model should be able to adapt to the new conditions by means
      of a recursive parameter estimation technique. Such an adaptive strategy will
      ensure that the most accurate model is used for the current conditions, and thus
      the most accurate model predictions are used in model-based control calculations.
      METHODS: In a retrospective analysis, empirical dynamic autoregressive exogenous
      input (ARX) models were identified from glucose-insulin data for nine type 1
      diabetes subjects in ambulatory conditions. Data sets consisted of continuous (5
      minute) glucose concentration measurements obtained from a continuous glucose
      monitor, basal insulin infusion rates and times and amounts of insulin boluses
      obtained from the subjects' insulin pumps, and subject-reported estimates of the
      times and carbohydrate content of meals. Two identification techniques were
      investigated: nonrecursive, or batch methods, and recursive methods. Batch models
      were identified from a set of training data, whereas recursively identified
      models were updated at each sampling instant. Both types of models were used to
      make predictions of new test data. For the purpose of comparison, model
      predictions were compared to zero-order hold (ZOH) predictions, which were made
      by simply holding the current glucose value constant for p steps into the future,
      where p is the prediction horizon. Thus, the ZOH predictions are model free and
      provide a base case for the prediction metrics used to quantify the accuracy of
      the model predictions. In theory, recursive identification techniques are needed
      only when there are changing conditions in the subject that require model
      adaptation. Thus, the identification and validation techniques were performed
      with both "normal" data and data collected during conditions of reduced insulin
      sensitivity. The latter were achieved by having the subjects self-administer a
      medication, prednisone, for 3 consecutive days. The recursive models were allowed
      to adapt to this condition of reduced insulin sensitivity, while the batch models
      were only identified from normal data. RESULTS: Data from nine type 1 diabetes
      subjects in ambulatory conditions were analyzed; six of these subjects also
      participated in the prednisone portion of the study. For normal test data, the
      batch ARX models produced 30-, 45-, and 60-minute-ahead predictions that had
      average root mean square error (RMSE) values of 26, 34, and 40 mg/dl,
      respectively. For test data characterized by reduced insulin sensitivity, the
      batch ARX models produced 30-, 60-, and 90-minute-ahead predictions with average
      RMSE values of 27, 46, and 59 mg/dl, respectively; the recursive ARX models
      demonstrated similar performance with corresponding values of 27, 45, and 61
      mg/dl, respectively. The identified ARX models (batch and recursive) produced
      more accurate predictions than the model-free ZOH predictions, but only
      marginally. For test data characterized by reduced insulin sensitivity, RMSE
      values for the predictions of the batch ARX models were 9, 5, and 5% more
      accurate than the ZOH predictions for prediction horizons of 30, 60, and 90
      minutes, respectively. In terms of RMSE values, the 30-, 60-, and 90-minute
      predictions of the recursive models were more accurate than the ZOH predictions,
      by 10, 5, and 2%, respectively. CONCLUSION: In this experimental study, the
      recursively identified ARX models resulted in predictions of test data that were
      similar, but not superior, to the batch models. Even for the test data
      characteristic of reduced insulin sensitivity, the batch and recursive models
      demonstrated similar prediction accuracy. The predictions of the identified ARX
      models were only marginally more accurate than the model-free ZOH predictions.
      Given the simplicity of the ARX models and the computational ease with which they
      are identified, however, even modest improvements may justify the use of these
      models in a model-based controller for an artificial beta cell.

PMID- 20144437
TI  - Measurement of glycated hemoglobin A1c from dried blood by turbidimetric
      immunoassay.
AB  - BACKGROUND: Glycated hemoglobin A1c (A1C) is an important marker in the diagnosis
      and treatment of diabetes. Dried blood measurement of A1C is useful in large
      scale epidemiological evaluation of A1C, especially to assess the impact of
      intervention programs. The possibility of using dried blood for measurement of
      A1C by the immunoturbidimetric method was explored in the present study. METHOD:
      Blood was collected from 30 patients, and blood spots were prepared and dried.
      The dried blood spot samples were kept for different lengths of time at 4 degrees
      C to assess stability. Glycated hemoglobin was measured in whole blood and dried
      blood on the day of collection as well as on days 10 and 15 by
      immunoturbidimetric method. RESULTS: The A1C values of 30 samples analyzed for
      comparison between whole blood estimation and dried blood ranged from 4.6% to
      9.9%. The mean A1C on the day of sample collection was 6.01% +/- 1.58% in fresh
      whole blood samples and 5.94% +/- 1.58 % in dried blood spots. A linear and
      highly correlated relationship was observed between dried blood A1C values and
      those in whole blood (r = 0.986 and intraclass correlation value = 0.993).
      Glycated hemoglobin values on day 10 and day 15 were comparable with the values
      on day 1 with a shift in mean of just 1% on day 10 and 3.04% on day 15.
      CONCLUSION: In conclusion, dried blood can be used for measurement of A1C by
      immunoturbidimetric method, and further stability of A1C measurement from dried
      blood for up to 15 days at 4 degrees C makes it an ideal matrix for
      transportation in developing countries like India.

PMID- 20144438
TI  - Delays in minimally invasive continuous glucose monitoring devices: a review of
      current technology.
AB  - Through the use of enzymatic sensors-inserted subcutaneously in the abdomen or ex
      vivo by means of microdialysis fluid extraction-real-time minimally invasive
      continuous glucose monitoring (CGM) devices estimate blood glucose by measuring a
      patient's interstitial fluid (ISF) glucose concentration. Signals acquired from
      the interstitial space are subsequently calibrated with capillary blood glucose
      samples, a method that has raised certain questions regarding the effects of
      physiological time lags and of the duration of processing delays built into these
      devices. The time delay between a blood glucose reading and the value displayed
      by a continuous glucose monitor consists of the sum of the time lag between ISF
      and plasma glucose, in addition to the inherent electrochemical sensor delay due
      to the reaction process and any front-end signal processing delays required to
      produce smooth traces. Presented is a review of commercially available, minimally
      invasive continuous glucose monitors with manufacturer reported device delays.
      The data acquisition process for the Medtronic MiniMed (Northridge, CA)
      continuous glucose monitoring system-CGMS Gold-and the Guardian RT monitor is
      described with associated delays incurred for each processing step. Filter
      responses for each algorithm are examined using in vitro hypoglycemic and
      hyperglycemic clamps, as well as with an analysis of fast glucose excursions from
      a typical meal response. Results demonstrate that the digital filters used by
      each algorithm do not cause adverse effects to fast physiologic glucose
      excursions, although nonphysiologic signal characteristics can produce greater
      delays.

PMID- 20144439
TI  - E-prescribing: clinical implications for patients with diabetes.
AB  - With the recent Center for Medicare and Medicaid Services and stimulus package
      incentives for health information technology, many clinicians are expected to
      adopt or enhance their use of e-prescribing systems. E-prescribing has nearly
      eradicated medication errors resulting from prescriber handwriting
      interpretations, yet several other patient-care and workflow benefits still
      remain a promise. As prescribers select or update their e-prescribing systems
      (whether stand-alone or integrated with electronic health records), close
      attention is needed to the e-prescribing application features and level of
      clinical decision support to avoid clinical blind spots, including incomplete or
      inaccurate patient medication lists, poor drop-down menu or screen design, and
      lack of clinically relevant and actionable drug interaction and drug allergy
      alerts. This article presents three case studies that highlight common e
      prescribing problems involving diabetes patients.

PMID- 20144440
TI  - The business of self-monitoring of blood glucose: a market profile.
AB  - The market for self-monitoring of blood glucose (SMBG) approached $8.8 billion
      worldwide in 2008. Yet despite dramatic double-digit growth in sales of SMBG
      products since 1980, the business is now facing declining prices and slower
      dollar growth. Given that SMBG meters and test strips are viewed by consumers and
      insurers as essentially generic products, it will be extremely challenging for
      new market entrants to displace well-entrenched existing competitors without a
      truly innovative technology. Also, in the face of declining glucose test strip
      prices, market expansion can only occur through identification of more of the
      undiagnosed diabetes population and convincing existing diabetes patients to
      adopt glucose testing or to test more frequently. Ultimately, a combination of
      technology innovations, patient education, and economic incentives may be needed
      to significantly expand the SMBG market and build sustainable long-term dollar
      growth for SMBG vendors.

PMID- 20144441
TI  - Juvenile diabetes research foundation artificial pancreas consortium update.

PMID- 20144442
TI  - Assessment of glycemic variability in continuous subcutaneous insulin infusion
      therapy in type 1 diabetes related to anthropometry and complication status.

PMID- 20144443
TI  - High frequency of cross-reacting antibodies against 2009 pandemic influenza
      A(H1N1) virus among the elderly in Finland.
AB  - Since May 2009, the pandemic influenza A(H1N1) virus has been spreading
      throughout the world. Epidemiological data indicate that the elderly are
      underrepresented among the ill individuals. Approximately 1,000 serum specimens
      collected in Finland in 2004 and 2005 from individuals born between 1909 and
      2005, were analysed by haemagglutination-inhibition test for the presence of
      antibodies against the 2009 pandemic influenza A(H1N1) and recently circulating
      seasonal influenza A viruses. Ninety-six per cent of individuals born between
      1909 and 1919 had antibodies against the 2009 pandemic influenza virus, while in
      age groups born between 1920 and 1944, the prevalence varied from 77% to 14%.
      Most individuals born after 1944 lacked antibodies to the pandemic virus. In
      sequence comparisons the haemagglutinin (HA) gene of the 2009 pandemic influenza
      A(H1N1) virus was closely related to that of the Spanish influenza and 1976 swine
      influenza viruses. Based on the three-dimensional structure of the HA molecule,
      the antigenic epitopes of the pandemic virus HA are more closely related to those
      of the Spanish influenza HA than to those of recent seasonal influenza A(H1N1)
      viruses. Among the elderly, cross-reactive antibodies against the 2009 pandemic
      influenza virus, which likely originate from infections caused by the Spanish
      influenza virus and its immediate descendants, may provide protective immunity
      against the present pandemic virus.

PMID- 20144444
TI  - Association of ciprofloxacin prescriptions to outpatients to Clostridium
      difficile infections.
AB  - To study if antibiotic treatment of outpatients had triggered Clostridium
      difficile infections (CDI), prescription numbers were compared with CDI-affected
      patient numbers. A strong correlation was observed for ciprofloxacin (R=0.917),
      suggesting that increased use of ciprofloxacin by outpatients contributed to
      increased numbers of CDI. These findings deserve further investigation as they
      may have an impact on future decisions regarding antibiotic prescribing.

PMID- 20144445
TI  - Estimating the impact of the 2009 influenza A(H1N1) pandemic on mortality in the
      elderly in Navarre, Spain.
AB  - We analysed mortality among people aged 65 years or older in Navarre, Spain in
      2009 and compared it with the mean for the same period of time in the previous
      three years. In the pandemic weeks 24 to 52 2009 we observed 4.9% more deaths
      than expected (p=0.0268). Excess mortality occurred during the circulation of
      seasonal influenza (8.0%, p=0.0367) and the first wave of pandemic influenza
      (9.9%, p=0.0079). In the second wave of pandemic influenza there was a non
      significant excess of deaths (5.2%, p=0.1166). Surveillance of laboratory
      confirmed severe influenza cases detected only one death in this age group.

PMID- 20144446
TI  - Higher all-cause mortality in children during autumn 2009 compared with the three
      previous years: pooled results from eight European countries.
AB  - The paper describes weekly fluctuations of all-cause mortality observed in eight
      European countries during the period between week 27 and 51, 2009, in comparison
      with three previous years. Our preliminary data show that the mortality reported
      during the 2009 influenza pandemic did not reach levels normally seen during
      seasonal influenza epidemics. However, there was a cumulative excess mortality of
      77 cases (1 per 100,000 population) in 5-14-year-olds, and possibly also among 0
      4-year-olds.

PMID- 20144447
TI  - Listeriosis outbreak caused by acid curd cheese Quargel , Austria and Germany
      2009.
AB  - We report an outbreak of listeriosis in Austria and Germany due to the
      consumption of Quargel cheese produced by an Austrian manufacturer. At the time
      of writing this report, the outbreak was known to account for 14 outbreak cases
      in 2009, including four cases with lethal outcome. On 23 January 2010, the cheese
      product was voluntarily withdrawn from the market.

PMID- 20144448
TI  - Calibration of European pharmacopoeia biological reference preparation for
      diphtheria vaccine (adsorbed) batch 4.
AB  - A collaborative study was organised by the European Directorate for the Quality
      of Medicines & HealthCare (EDQM) and the National Institute for Biological
      Standards and Control (NIBSC) to establish replacement batches of the current
      World Health Organization (WHO) International Standard (IS) and European
      Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Diphtheria
      Vaccine (Adsorbed). Two candidates were assayed against the current 3rd IS/BRP
      batch 3 for Diphtheria Vaccine (Adsorbed) with an assigned potency of 160
      IU/ampoule using established WHO/Ph. Eur. challenge methods in guinea pigs as
      described in the Ph. Eur. general chapter 2.7.6. Assay of diphtheria vaccine
      (adsorbed). Twenty-one laboratories (regulatory organisations and manufacturers)
      from 17 countries participated in the study. Two freeze-dried, stabilised
      diphtheria vaccine (adsorbed) preparations were included in the study:
      Preparation A (07/218) and Preparation B (07/216). As stocks of the 3rd IS were
      very low, the Diphtheria vaccine (adsorbed) BRP batch 3, which is identical to
      the 3rd IS but which was kept at the EDQM, was used for the calibration (coded
      Preparation C). The majority of participants performed 2 independent challenge
      tests. Five laboratories performed the intradermal challenge test, 16
      laboratories performed the systemic challenge test. For Preparation A, the
      unweighted geometric mean potency estimate (with 95 % confidence limits) for all
      laboratories that provided valid results (n = 17) was 97.2 (89.5-105.6)
      IU/ampoule. For systemic challenge assays (n = 14) the unweighted geometric mean
      potency was 97.0 (88.1-106.7) IU/ampoule. The between-laboratory GCV was 17.4 %
      for all assays and 18.0 % for systemic challenge assays. There was no significant
      difference in estimates for intradermal or systemic challenge (p = 0.45). For
      Preparation B the unweighted geometric mean potency estimate (with 95 %
      confidence limits) for all laboratories that provided valid results (n = 19) was
      213.4 (185.7-245.4) IU/ampoule. For systemic challenge assays (n = 14) the
      unweighted geometric mean potency was 202.0 (170.4-239.5) IU/ampoule. The between
      laboratory GCV was 33.5 % for all assays and 34.3 % for systemic challenge
      assays. For both preparations there is a good agreement between results obtained
      from systemic and intradermal challenge methods. Greater between-laboratory
      variability was observed for systemic assays than for intradermal challenge
      assays, although the small number of intradermal assays performed in the study
      makes comparison difficult. The GCV for all assays was 17.4 % for potency
      estimates of Preparation A and 33.5 % for Preparation B. This compares favourably
      with the calibration of the current standard where the between-laboratory GCV for
      all assays was 28.3 %. From the collaborative study both Preparation A and
      Preparation B appeared suitable to replace the current Diphtheria vaccine
      (adsorbed) BRP batch 3. Due to the similarity of Preparation A with the current
      BRP batch 3, the Ph. Eur. Commission adopted Preparation A as Diphtheria vaccine
      (adsorbed) BRP batch 4 with an assigned potency of 97 IU/ampoule.

PMID- 20144449
TI  - Collaborative study for the validation of alternative in vitro potency assays for
      human tetanus immunoglobulin.
AB  - The European Pharmacopoeia (Ph. Eur.) monograph Human tetanus immunoglobulin
      (0398) gives a clear outline of the in vivo assay to be performed to determine
      the potency of human tetanus immunoglobulins during their development.
      Furthermore, it states that an in vitro method shall be validated for the batch
      potency estimation. Since no further guidance is given on the in vitro assay,
      every control laboratory concerned is free to design and validate an in-house
      method. At the moment there is no agreed in vitro method available. The aim of
      this study was to validate and compare 2 alternative in vitro assays, i.e. an
      enzyme-linked immunoassay (EIA) and a toxoid inhibition assay (TIA), through an
      international collaborative study, in view of their eventual inclusion into the
      Ph. Eur.. The study was run in the framework of the Biological Standardisation
      Programme (BSP), under the aegis of the European Commission and the Council of
      Europe. The collaborative study reported here involved 21 laboratories (public
      and industry) from 15 countries. Initially, 3 samples with low, medium and high
      potencies were tested by EIA and TIA. Results showed good reproducibility and
      repeatability of the 2 in vitro methods. The correlation of the data with the in
      vivo potency assigned by the manufacturers however appeared initially poor for
      high potency samples. Thorough re-examination of the data showed that the in vivo
      potencies assigned by the manufacturers had to be corrected: one for potency loss
      at the time of in vitro testing and one because of a reporting error. After these
      corrections the values obtained by in vivo and in vitro methods were in close
      agreement. A supplementary collaborative work was carried out to validate the 2
      methods for immunoglobulin products with high potencies. Eight laboratories
      (public and industry) took part in this additional study to test 3 samples with
      medium and high potencies by EIA and TIA. Results confirmed that the 2
      alternative methods are comparable in terms of assay repeatability, precision and
      reproducibility. In all laboratories, both methods discriminated between the low,
      medium and high potency samples. Analysis of the data collected in this study
      showed a good correlation between EIA and TIA potency estimates as well as a
      close agreement between values obtained by in vitro and in vivo methods. The
      study demonstrated that EIA and TIA are suitable quality control methods for
      polyclonal human tetanus immunoglobulin, which can be standardised in a quality
      control laboratory using a quality assurance system. Consequently, the Ph. Eur.
      Group of Experts 6B on Human Blood and Blood products decided in April 2009 to
      include both methods as examples in the Ph. Eur. monograph 0398 on Human Tetanus
      immunoglobulin.

PMID- 20144450
TI  - Collaborative study on a Guinea pig serological method for the assay of acellular
      pertussis vaccines.
AB  - An international collaborative study (coded BSP083) was performed under the aegis
      of the Biological Standardisation Programme supported by the Council of Europe
      and the European Commission, with the aim of replacing the in vivo challenge
      assays for potency determination of combined acellular pertussis (aP) vaccines by
      a refined procedure also allowing reduction of animal use. This study
      investigates whether the immunogenicity of aP vaccine components could be assayed
      in a guinea pig (gp) serology model, using the same vaccine immunising doses as
      for D and T components potency testing, instead of using separate animals as is
      currently done. The BSP83 project is a follow up of 3 former collaborative
      studies (coded BSP019, BSP034 and BSP035) on serological methods for the potency
      testing of tetanus (T) and diphtheria (D) vaccines for human use. The use of gp
      instead of mice serology has the advantage of providing a larger volume of good
      quality antiserum for the assay of several vaccine components in the same sample,
      hence providing the opportunity for animal sparing. The results of Phase I of the
      study demonstrated that gp serology may be a useful method for the immunogenicity
      assay of acellular pertussis vaccines. This was confirmed in Phase II of the
      study, using 7 different combined aP vaccines in an international collaborative
      study involving 17 laboratories from both public and private sectors. Clear dose
      response relationships were observed for different vaccines by ELISA, for
      antibodies against aP antigens, i.e. pertussis toxin (PT), filamentous
      haemagglutinin (FHA), fimbrial agglutinogens-2/3 (Fim 2/3) and pertactin (PRN).
      Intra- and inter-laboratory variations of aP ELISA results were found to be
      within an acceptable range. For some combined vaccines, however, the range of
      vaccine dilutions for immunisation confirmed to be optimal for D and T potency
      testing may not provide optimal dose-response for all aP components. Method
      adjustments may thus be required and suitability should therefore be demonstrated
      for each vaccine combination and product prior to the application of this assay.
      The results of this study support the use of the gp serological method for the
      determination of the immunogenicity of aP vaccines. The application of the method
      for batch release testing of combined D, T and aP vaccines could significantly
      contribute to the implementation of the 3R principles through reduction of animal
      use and improved animal welfare, whilst reducing costs. As an outcome of this
      study, the Group of Experts No. 15 on Sera and Vaccines of the European
      Pharmacopoeia (Ph. Eur.) decided in February 2009 to include the gp serological
      assay as an example in the Ph. Eur. General chapter 2.7.16. on acellular
      pertussis vaccine assay.

PMID- 20144451
TI  - Establishment of the Ph. Eur. BRP for varicella vaccine batch 1.
AB  - The European Pharmacopoeia (Ph. Eur.) monograph for varicella vaccine (live)
      (0648) requires a vial of an appropriate reference material to be titred in
      triplicate to validate each assay and the virus concentration of the reference
      preparation is monitored using a control chart to determine the assay
      consistency. An international collaborative study involving 9 participants from 7
      countries and including both OMCLs and manufacturers was carried out to establish
      a common reference material for this purpose and establish a Ph. Eur. Biological
      Reference Preparation. Two candidate reference preparations (X and Y), obtained
      from 2 different EU manufacturers, were assayed by the participants using their
      in-house PFU assay methods. Both candidates were found to be suitable for this
      purpose. Based on logistical considerations, candidate X (4.37 log(10)0 PFU/vial)
      has been established as BRP batch 1 of varicella vaccine (live) and was adopted
      at the June 2009 session of the European Pharmacopoeia Commission for immediate
      use. Candidate Y (3.82 log(10) PFU/vial) will be established as BRP batch 2 upon
      depletion of BRP batch 1 provided that the stability data supports this.

PMID- 20144452
TI  - A crescent-shaped spindle for improved dissolution testing.
AB  - Current practices of drug dissolution testing require that the experimental
      conditions, such as medium and its volume and apparatus and its associated
      stirrer rotation speed, be established for each test product to achieve certain
      'expected' dissolution characteristics or results. In reality, however, the
      purpose of dissolution testing should be to determine potentially unknown
      dissolution results reflective of a test product based on its formulation and/or
      manufacturing attributes. For appropriate testing, in particular for comparative
      purposes, the experimental conditions must be the same or consistent from product
      to product i.e. product independent. This article describes a newly developed
      spindle, known as crescent-shaped, which can easily be installed in the vessel
      based dissolution apparatuses (basket and paddle) to provide a product
      independent dissolution testing approach for improved drug dissolution
      assessments. The new spindle provides an improved stirring and mixing
      environment, leading to better characterization of pharmaceutical products. The
      use of the crescent-shaped spindles offers additional significant advantages over
      the current practices, such as: (1) allows analyses using a single method,
      compared to hundreds as currently required, for both immediate and extended
      released products having the same or different active ingredients; (2) provides
      improved dissolution characteristics of products by avoiding false slow release
      properties for fast release type products; (3) simplifies testing by avoiding the
      necessity of developing separate QC and bio-relevant dissolution methods; (4)
      provides a rugged testing environment free from common sensitivities, in
      particular to de-aeration and vibration effects. Considering that the new design
      provides significant advantages, the spindle may be considered for inclusion in
      the Ph. Eur., as an option, in the general chapter on dissolution testing.

PMID- 20144453
TI  - Development of an alternative method for determination of terpene lactones in
      ginkgo dry extract.
AB  - A new liquid chromatographic mass spectrometric (LC-MS) method for determination
      of terpene lactones in ginkgo dry extract has been developed. The new method has
      several advantages over the existing European Pharmacopoeia (Ph. Eur.) method for
      analysis of terpene lactones in ginkgo dry extract, the major ones being a very
      simple sample pre-treatment and an excellent selectivity. 5 terpene lactones were
      analysed with a precision expressed as relative standard deviation (RSD) of 0.4
      3.1% and a mean relative error (RE) within +/-4.6%. The method was used to
      analyse 9 samples of ginkgo dry extracts from 3 different extract producers. The
      content of bilobalide was found to be in the range of 2.6-3.4% in all samples,
      whereas the sum of ginkgolides A, B and C was found to be in the range of 3.0
      3.6%. Ginkgolide J was found in the range of 0.3-0.6%.

PMID- 20144454
TI  - Sub-visible particle quantitation in protein therapeutics.
AB  - Biologics represent a large and growing segment of the therapeutic medicinal
      market. Sub-visible particles present in these products are a product quality
      attribute and a potential patient safety concern yet to be fully explored. Early
      and consistent particle quantitation and control throughout the product life
      cycle of these drugs from development to commercial lot release is critical in
      mitigating any concerns. This requires appropriate analytical methods which can
      be applied to biopharmaceuticals across a large variety of protein concentrations
      and modes of administration. The compendial light obscuration method for
      quantitating sub-visible particles in small volume parenterals is not ideally
      suited for therapeutic biologics. Approaches to modify the current compendial
      method so that it is applicable to biologics, including appropriate sample
      preparation, reduced assay sample volume, increased sizing information, and
      development of an appropriate sampling plan, are presented in this article.
      Successful applications of a modified light obscuration method to therapeutic
      protein products are demonstrated, and a strategy to utilise complimentary
      methods and techniques at different phases of product development is discussed.

PMID- 20144455
TI  - Maxillary sinus floor elevation using a tissue engineered bone complex with BMP-2
      gene modified bMSCs and a novel porous ceramic scaffold in rabbits.
AB  - OBJECTIVES: To study the effects of maxillary sinus floor elevation by a tissue
      engineered bone complex with bone morphogenetic protein-2 (BMP-2) gene modified
      bone marrow stromal cells (bMSCs) and a novel porous ceramic scaffold (OsteoBone)
      in rabbits. MATERIALS AND METHODS: bMSCs derived from New Zealand rabbit bone
      marrow were cultured and transduced with adenovirus AdBMP-2 and with AdEGFP gene
      (without BMP-2 gene sequence) as a control, respectively, in vitro. These bMSCs
      were then combined with OsteoBone scaffold at a concentration of 2 x
      10(7)cells/ml and used to elevate the maxillary sinus floor in rabbits. Eight
      rabbits were randomly allocated into groups and sacrificed at weeks 2 and 4. For
      each time point, 8 maxillary sinus floor elevation surgeries were made
      bilaterally in 4 rabbits for the two groups (n=4 per group): group A (AdBMP-2
      bMSCs/material) and group B (AdEGFP-bMSCs/material). All samples were evaluated
      by histologic and histomorphometric analysis. RESULTS: The augmented maxillary
      sinus height was maintained for both groups over the entire experimental period,
      while new bone area increased over time for group A. At week 4 after operation,
      bone area in group A was significantly more than that in group B (P<0.05), and
      was more obviously detected in the center of the elevated space. Under a confocal
      microscope, green fluorescence in newly formed bone was observed in the EGFP
      group, which suggests that those implanted bMSCs had contributed to the new bone
      formation. CONCLUSION: bMSCs modified with AdBMP-2 gene can promote new bone
      formation in elevating the rabbit maxillary sinus. OsteoBone scaffold could be an
      ideal carrier for gene enhanced bone tissue engineering.

PMID- 20144456
TI  - The development of perceptual grouping biases in infancy: a Japanese-English
      cross-linguistic study.
AB  - Perceptual grouping has traditionally been thought to be governed by innate,
      universal principles. However, recent work has found differences in Japanese and
      English speakers' non-linguistic perceptual grouping, implicating language in non
      linguistic perceptual processes (Iversen, Patel, & Ohgushi, 2008). Two
      experiments test Japanese- and English-learning infants of 5-6 and 7-8 months of
      age to explore the development of grouping preferences. At 5-6 months, neither
      the Japanese nor the English infants revealed any systematic perceptual biases.
      However, by 7-8 months, the same age as when linguistic phrasal grouping
      develops, infants developed non-linguistic grouping preferences consistent with
      their language's structure (and the grouping biases found in adulthood). These
      results reveal an early difference in non-linguistic perception between infants
      growing up in different language environments. The possibility that infants'
      linguistic phrasal grouping is bootstrapped by abstract perceptual principles is
      discussed.

PMID- 20144457
TI  - The time course of vasoconstriction and endothelin receptor A expression in
      pulmonary arterioles of mice continuously exposed to ambient urban levels of air
      pollution.
AB  - The present study aimed to verify the time course of the effects of environmental
      levels of urban air pollution toxicity on lung arterioles. BALB/c mice (n=56)
      were continuously exposed to selective chambers equipped with (filtered, F) or
      without (non-filtered, NF) filter devices for particles and toxic gases for
      24h/day, over 14, 21, 30 or 45 days. After exposure, we evaluated the lumen-wall
      relationship (an estimator of arteriolar narrowing), endothelial nitric oxide
      synthase (eNOS) and endothelin type A receptor (ETAr) expression in the vascular
      wall and inflammatory influx of the peribronchiolar area. Concentrations of fine
      particulate matter (PM<or=2.5 microg/m(3)), nitrogen dioxide (NO(2)), black smoke
      (BS), humidity and temperature in both the environment and inside the chambers
      were measured daily. Filters cleared 100% of BS and 97% of PM inside the F
      chamber. The arteriole wall of the lungs of mice from NF chamber had an increased
      ETAr expression (p<or=0.042) concomitant to a decrease in the lumen/wall ratio
      (p=0.02) on the early days of exposure, compared to controls. They also presented
      a progressive increment of inflammatory influx in the peribronchiolar area during
      the study (p=0.04) and decrement of the eNOS expression on the 45th day of
      exposure in both vascular layers (p<or=0.03). We found that after 14 days of
      exposure, the ambient levels of air pollutants in Sao Paulo induced
      vasoconstriction that was associated with an increase in ETAr expression. These
      vascular results do not appear to be coupled to the progressive inflammatory
      influx in lung tissue, suggesting a down-regulation of vasoconstrictive
      mechanisms through an imbalance in the cytokines network. It is likely that these
      responses are protective measures that decrease tissue damage brought about by
      continuous exposure to air pollutants.

PMID- 20144458
TI  - Are serum cholesterol levels associated with silent brain infarcts? The Seiryo
      Clinic Study.
AB  - OBJECTIVE: High levels of serum cholesterol are associated with the risk of
      stroke. However, the association of serum cholesterol with silent brain infarcts
      (SBIs) is unclear. We investigated the association between SBI and various
      clinical factors. METHODS: We conducted a cross-sectional study that included 324
      apparently healthy Japanese men (mean age 53.8+/-9.2 years). Combinations of
      three types of scan (T1-weighted, T2-weighted and FLAIR images) were used to
      detect and discriminate SBI. RESULTS: Serum cholesterol was significantly
      associated with SBI [total cholesterol, odds ratio (OR) 3.75 (95% confidence
      interval (CI) 1.45-9.68); LDL-cholesterol, OR 2.54 (95% CI 1.03-6.27), and non
      HDL-cholesterol, OR 2.54 (95% CI 1.03-6.27)] after adjustment for age, smoking
      status, serum triglycerides, maximal-intima-media thickness, obesity,
      hypertension, diabetes mellitus, hyperuricemia, coronary heart disease and lipid
      lowering agent use. CONCLUSION: Our cross-sectional data suggest that serum
      cholesterol levels are associated with SBI independently of known confounders.

PMID- 20144459
TI  - Separation of model mixtures of epsilon-globin positive fetal nucleated red blood
      cells and anucleate erythrocytes using a microfluidic device.
AB  - Microfluidic devices are capable of separating microparticles and cells. We
      developed and tested the efficiency of silicon cross-flow microfilters for the
      separation of primitive fetal nucleated red blood cells (FNRBCs) and adult
      anucleate red blood cell (AARBCs) from model mixtures. Stepwise improvements over
      three generations of device design resulted in an increasing trend in the
      recovery of FNRBCs. We obtained a recovery of FNRBCs (74.0+/-6.3%, p<0.05, n=5)
      using the third generation device, with a depletion of 46.5+/-3.2% AARBCs from
      the cell mixture. The purity of FNRBCs in the enriched fraction was enhanced by a
      factor of 1.7-fold.

PMID- 20144460
TI  - Comparison of QuEChERS sample preparation methods for the analysis of pesticide
      residues in fruits and vegetables.
AB  - This article describes the comparison of different versions of an easy, rapid and
      low-cost sample preparation approach for the determination of pesticide residues
      in fruits and vegetables by concurrent use of gas and liquid chromatography (GC
      and LC) coupled to mass spectrometry (MS) for detection. The sample preparation
      approach is known as QuEChERS, which stands for "quick, easy, cheap, effective,
      rugged and safe". The three compared versions were based on the original
      unbuffered method, which was first published in 2003, and two interlaboratory
      validated versions: AOAC Official Method 2007.01, which uses acetate buffering,
      and European Committee for Standardization (CEN) Standard Method EN 15662, which
      calls for citrate buffering. LC-MS/MS and GC-MS analyses using each method were
      tested from 50 to 1000ng/g in apple-blueberry sauce, peas and limes spiked with
      32 representative pesticides. As expected, the results were excellent (overall
      average of 98% recoveries with 10% RSD) using all 3 versions, except the
      unbuffered method gave somewhat lower recoveries for the few pH-dependent
      pesticides. The different methods worked equally well for all matrices tested
      with equivalent amounts of matrix co-extractives measured, matrix effects on
      quantification and chemical noise from matrix in the chromatographic backgrounds.
      The acetate-buffered version gave higher and more consistent recoveries for
      pymetrozine than the other versions in all 3 matrices and for thiabendazole in
      limes. None of the versions consistently worked well for chlorothalonil, folpet
      or tolylfluanid in peas, but the acetate-buffered method gave better results for
      screening of those pesticides. Also, due to the recent shortage in acetonitrile
      (MeCN), ethyl acetate (EtOAc) was evaluated as a substitute solvent in the
      acetate-buffered QuEChERS version, but it generally led to less clean extracts
      and lower recoveries of pymetrozine, thiabendazole, acephate, methamidophos,
      omethoate and dimethoate. In summary, the acetate-buffered version of QuEChERS
      using MeCN exhibited advantages compared to the other tested methods in the
      study.

PMID- 20144461
TI  - Disposable pipette extraction for the analysis of pesticides in fruit and
      vegetables using gas chromatography/mass spectrometry.
AB  - Organochlorine, organophosphate pesticides and fungicides in fruits and
      vegetables were analyzed using disposable pipette extraction (DPX) followed by
      gas chromatography-mass spectrometry-selective ion monitoring (GC/MS-SIM). The
      intrinsic rapid mixing capabilities of DPX result in fast and efficient
      extractions, and eluates are concentrated by using minimal elution solvent
      volumes rather than solvent evaporation methods. Matrix-matched calibrations were
      performed with reversed phase mechanisms (DPX-RP), and the limits of detection
      (LOD) were determined to be lower than 0.1 microg/mL for all targeted pesticides
      in carrot and orange sample matrices. Coefficients of determination (r(2)) were
      greater than 0.995 for most studied pesticides. DPX-RP exhibited recoveries
      between 72 and 116% for nonpolar and slightly polar pesticides (logP>2) with most
      of the recoveries over 88%. Only very polar pesticides (e.g., acephate,
      mathamidophos) were not extracted well using DPX-RP.

PMID- 20144462
TI  - Characterization of the volatile fraction emitted by Pinus spp. by one- and two
      dimensional chromatographic techniques with mass spectrometric detection.
AB  - The chemical composition of the needles of P. pinea, P. pinaster, P. halepensis,
      P. nigra, P. brutia, P. patula, P. radiata, P. taeda, P. elliotti, P. kesiya, P.
      sylvestris and P. eldarica was investigated. Headspace solid-phase
      microextraction and steam distillation extraction were used to collect the
      volatile fractions. Samples were analyzed using one-dimensional gas
      chromatography (1D-GC) and comprehensive two-dimensional gas chromatography
      (GCxGC) associated with a quadrupole and a time-of-flight mass detectors. Results
      showed that the analytical capabilities of 1D-GC are partially limited by the
      separation power of the columns. The higher sensibility and the absence of peak
      skewing of the time-of-flight mass analyzer, with the use of automated peak
      finding and deconvolution algorithms, allowed for the detection of trace
      components with qualitative full spectra and the extraction of true mass spectra
      from coeluting compounds, promoting their reliable identification and thus
      significantly improving results obtained by 1D-GC/MS, when using a quadrupole
      mass analyzer. The use of GC x GC resulted in enhanced separation efficiency and
      increased signal to noise ratio (sensitivity) of the analytes, maximizing mass
      spectra quality and improving compound detection and identification. This work
      shows the use of 1D-GC/ToFMS for the analysis of pine needles volatiles,
      achieving the detection of 177 compounds, that is more than twice the number
      previously identified by standard 1D-GC/MS. The analysis by GC x GC for the same
      sample allowed the detection of 212 compounds. The enantioselective GC x GC
      analysis performed for all the Pinus spp. under study achieved the detection of
      422 different compounds. Cross-over phenomena according to operational conditions
      are highlighted and discussed.

PMID- 20144463
TI  - Dispersive liquid-liquid microextraction applied to isolation and concentration
      of alkylphenols and their short-chained ethoxylates in water samples.
AB  - Dispersive liquid-liquid microextraction (DLLME) coupled with high-performance
      liquid chromatography with fluorescence detector was applied for the
      determination of alkylphenols and their short-chained ethoxylates in water
      samples. Development of DLLME procedure included optimisation of some important
      parameters such as kind and volume of extracting and dispersing solvents. Under
      optimised conditions 50 microL of trichloroethylene in 1.5 mL of acetone were
      rapidly injected into 5 mL of a water sample. After centrifuging the organic
      phase containing the analytes was taken for evaporation with a gentle nitrogen
      purge and reconstituted to 50 microL of acetonitrile. The aliquot of this
      solution was analysed with the use of HPLC. For octylphenol (OP) and octylphenol
      ethoxylates (OPEOs) linearity was satisfactory in the range 8-1000 microg L(-1)
      and for nonylphenol (NP) and nonylphenol ethoxylates (NPEOs) linearity was in the
      range from 50 to about 3000 microg L(-1). Limit of quantitation was 0.1 microg L(
      1) for OP and OPEOs and 0.3 microg L(-1) for NP and NPEOs. Satisfactory
      recoveries between 66 and 79% were obtained for environmental samples. The
      results showed that DLLME is a simple, rapid and sensitive analytical method for
      the preconcentration of trace amounts of alkylphenols and their ethoxylates in
      environmental water samples.

PMID- 20144464
TI  - Chronic childhood adversity and onset of psychopathology during three life
      stages: childhood, adolescence and adulthood.
AB  - BACKGROUND: The aim is to report the individual and joint effects of a range of
      chronic childhood adversities on the first onset of a broad range of psychiatric
      disorders, and to evaluate their impact at different stages of the life course in
      a representative sample of the Mexican population. METHOD: The data is from the
      Mexican National Comorbidity Survey (M-NCS), a stratified, multistage area
      probability sample of persons aged 18-65. The WHO World Mental Health Composite
      International Diagnostic Interview (WMH-CIDI) measured 12 childhood adversities,
      20 psychiatric disorders and ages of onset. Discrete-time survival models were
      performed to estimate the odds of disorder onset. RESULTS: In bivariate models,
      all adversities (except economic adversity and parental death) were significant
      predictors of psychopathology; however in multivariate models which correct for
      the clustering of adversities, family dysfunction and abuse adversities were the
      strongest and most consistent predictors of all four classes of psychopathologies
      examined (mood, anxiety, substance use and externalizing), and for the most part,
      over all three life course stages (childhood, adolescence and adulthood). The
      effect of the number of adversities was nonlinear such that although the odds of
      disorder onset increased with increasing numbers of adversities, the odds
      increased at a decreasing rate. CONCLUSIONS: Childhood family dysfunction and
      abuse is a strong predictor of the onset of psychopathology throughout the life
      course, consistent with evidence for the enduring effects of chronic stress on
      brain structures involved in many psychiatric disorders and with stress
      sensitization models of psychopathology.

PMID- 20144465
TI  - Parry-Romberg syndrome associated with unusual intracranial vascular
      malformations and Phthisis bulbi.
AB  - Neurovascular anomalies of Parry-Romberg syndrome have been reported
      infrequently. We report a case of Parry-Romberg syndrome with hypoplastic left
      internal carotid, middle cerebral, anterior cerebral, posterior communicating and
      posterior cerebral artery. The patient presented with partial seizures,
      hemiparesis and phthisis bulbi.

PMID- 20144466
TI  - A giant MS plaque mimicking PML during natalizumab treatment.
AB  - We describe a patient with a giant MS plaque developing during natalizumab
      administration whose clinical presentations mimicked PML. This 27year-old man
      developed new onset confusion, altered behavior, left hemianesthesia and
      worsening dysarthria, gait and balance with a new, large, rim-enhancing,
      temporoparietal subcortical lesion after four infusions of natalizumab.
      Cerebrospinal JC virus polymerase chain reaction was negative. No neutralizing
      antibody to natalizumab was detected. Following discontinuation of natalizumab,
      plasma exchange, and a single dose of 1000mg of methylprednisolone, he
      demonstrated clinical and radiographic improvement. Distinguishing PML from MS
      may be very difficult in some instances. The frequency with which an aggressive
      demyelinating disorder due to MS occurs during treatment with natalizumab remains
      to be determined.

PMID- 20144467
TI  - Spermatogenesis and sperm structure of Acerella muscorum, (Ionescu, 1930)
      (Hexapoda, Protura).
AB  - The general organization of the male genital system, the spermatogenesis and the
      sperm structure of the proturan Acerella muscorum have been described. At the
      apex of testis apical huge cells are present; their cytoplasm contains a
      conventional centriole, a large amount of dense material and several less
      electron-dense masses surrounded by mitochondria. Spermatocytes have normal
      centrioles and are interconnected by cytoplasmic bridges. Such bridges seem to be
      absent between spermatid cells and justify the lack of synchronization of cell
      maturation. Spermatids are almost globular cells with a spheroidal nucleus and a
      large mass of dense material corresponding to the centriole adjunct. Within this
      mass a centriole is preserved. Mitochondria of normal structure are located
      between the nucleus and the plasma membrane. The spermatids are surrounded by a
      thick membrane. No flagellar structure is formed. Sperm have a compact spheroidal
      nucleus, a large cap of centriole adjunct material within which a centriole is
      still visible. A layer of mitochondria is located over the nucleus. The cytoplasm
      is reduced in comparison to spermatids; many dense bodies are interspersed with
      sperm in the testicular lumen. The sperm are small, immotile cells of about 2.5
      3microm in diameter.

PMID- 20144468
TI  - The human papillomavirus type 16 E5 oncoprotein synergizes with EGF-receptor
      signaling to enhance cell cycle progression and the down-regulation of p27(Kip1).
AB  - E5 oncoprotein activity from high risk human papillomaviruses (HPVs) is
      associated with growth factor receptor signaling, but the function of this
      protein is not well understood. In this study, we investigated the role of HPV-16
      E5 on the cell cycle progression during EGF-stimulation. Wild-type and NIH 3T3
      cells over-expressing human EGF-receptor were transfected with HPV-16 E5 gene and
      the cell cycle progression was characterized. This analysis showed that the E5
      expressing cells increased DNA synthesis (S-phase) by around 40%. Cell cycle
      protein analysis of E5-expressing cells showed a reduction in the half-life of
      p27(Kip1) protein as compared to control cells (18.4 vs. 12.7 h), an effect that
      was enhanced in EGF-stimulated cells (12.8 vs. 3.6 h). Blockage of EGF-receptor
      activity abrogated E5 signals as well as p27(Kip1) down-regulation. These results
      suggest that E5 and the EGF-receptor cooperate to enhance cell cycle entry and
      progression through regulating p27(Kip1) expression at protein level.

PMID- 20144469
TI  - Histochemical studies on mucin-rich cells in the digestive tract of a teleost,
      the Buenos Aires tetra (Hyphessobrycon anisitsi).
AB  - Types of mucus cells and mucins in the epithelial cell layer throughout the
      digestive tract of the Buenos Aires tetra (Hyphessobrycon anisitsi) are described
      and compared. The mucin was produced in three different cell types: in sac-like
      cells in the esophagus, in surface epithelial cells in the stomach and in goblet
      cells in the caeca and intestine. Nearly the entire esophageal epithelial cell
      layer consisted of mucus cells, filled by both neutral mucin and non-sulfated
      acidic mucin. The gastric mucin occurred in the distal area of the surface
      epithelial cells only and contained mainly neutral proteoglycans rich in
      glucosamine and some galactosamine and sialic acid. The goblet cells contained
      mainly non-sulfated acidic mucin in the caeca and sulfated acidic mucin
      throughout the entire intestine. Much glucosamine and some galactosamine and
      sialic acid occurred regularly in these cells in both the caeca and intestine.
      The observation that goblet cells often displayed colors ranging between blue and
      purple-magenta when alcian blue staining was followed by periodic acid-Schiff
      (PAS), or between blue and red-brown when the alcian blue was followed by neutral
      red, may reflect different ages or stages of development and differentiation for
      these cells. The highly variable affinities to wheat germ agglutinin (WGA-lectin)
      seen in these cells in the present study strengthens this view. However, such
      results may also suggest a true cellular heterogeneity reflecting various roles
      in lubrication, immunological defence, digestion and absorption.

PMID- 20144470
TI  - Paraneoplastic opsoclonus-myoclonus syndrome secondary to immature ovarian
      teratoma.

PMID- 20144471
TI  - Surgical outcomes of robotic-assisted surgical staging for endometrial cancer are
      equivalent to traditional laparoscopic staging at a minimally invasive surgical
      center.
AB  - OBJECTIVE: To compare peri- and post-operative complications and outcomes of
      robotic-assisted surgical staging with traditional laparoscopic surgical staging
      for women with endometrial cancer. METHODS: A retrospective chart review of cases
      of women undergoing minimally invasive total hysterectomy and pelvic and para
      aortic lymphadenectomy by a robotic-assisted approach or traditional laparoscopic
      approach was conducted. Major intraoperative complications, including vascular
      injury, enterotomy, cystotomy, or conversion to laparotomy, were measured.
      Secondary outcomes including operative time, blood loss, transfusion rate, number
      of lymph nodes retrieved, and the length of hospitalization were also measured.
      RESULTS: 275 cases were identified-102 patients with robotic-assisted staging and
      173 patients with traditional laparoscopic staging. There was no significant
      difference in the rate of major complications between groups (p=0.13). The mean
      operative time was longer in cases of robotic-assisted staging (237 min vs. 178
      min, p<0.0001); however, blood loss was significantly lower (109 ml vs. 187 ml,
      p<0.0001). The mean number of lymph nodes retrieved were similar between groups
      (p=0.32). There were no significant differences in the time to discharge, re
      admission, or re-operation rates between the two groups. CONCLUSION: Robotic
      assisted surgery is an acceptable alternative to laparoscopy for minimally
      invasive staging of endometrial cancer. In addition to the improved ease of
      operation, visualization, and range of motion of the robotic instruments, robotic
      surgery results in a lower mean blood loss, although longer operative time. More
      data are needed to determine if the rates of urinary tract injuries and other
      surgical complications can be reduced with the use of robotic surgery.

PMID- 20144472
TI  - Speaking the same language: The World Allergy Organization Subcutaneous
      Immunotherapy Systemic Reaction Grading System.
AB  - Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic
      rhinitis, asthma and venom hypersensitivity and has the potential of producing
      serious life-threatening anaphylaxis. Adverse reactions are generally classified
      into 2 categories: local reactions, which can manifest as redness, pruritus, and
      swelling at the injection site, and systemic reactions (SRs). SRs can range in
      severity from mild rhinitis to fatal cardiopulmonary arrest. Early administration
      of epinephrine, which is the treatment of choice to treat anaphylaxis, may
      prevent the progression of an SR to a more serious life-threatening problem.
      Although there is little debate about using epinephrine to treat a SCIT SR, there
      is a lack of consensus about when it should be first used. A uniform
      classification system for grading SCIT SRs will be helpful in assessing more
      accurately when epinephrine should be administered. The primary purpose of this
      article is to discuss the proposed grading system for SCIT SRs.

PMID- 20144473
TI  - Brief report: adolescents under missile attacks: sense of coherence as a mediator
      between exposure and stress-related reactions.
AB  - Employing the salutogenic approach (Antonovsky, 1987), this pilot study aimed at
      exploring the mediation effect of Sense of Coherence (SOC) on the relationships
      between exposure to missile attacks and stress-related reactions among
      adolescents. A strong SOC means a tendency to see the world as more
      comprehensible, manageable and meaningful. Data were gathered during August 2006
      (Second Lebanon War) from 230 Israeli adolescents, 12-18 years old. Adolescents
      filled out self-reported questionnaires, including demographics, level of
      physical exposure, SOC, Scale of Psychological Distress (SPD), State Anxiety and
      State Anger. Exposure to missile attacks was found to be significantly positively
      linked to stress reactions; exposure was negatively linked to SOC which was also
      negatively linked to stress reactions. The mediation hypothesis was supported,
      with SOC mediating the effect of exposure to missile attacks on stress reactions.
      It seems that SOC may have a protective effect against stress reactions among
      adolescents exposed to political violence. This should be further studied in a
      longitudinal research.

PMID- 20144474
TI  - Density functional theory simulation of titanium migration and reaction with
      oxygen in the early stages of oxidation of equiatomic NiTi alloy.
AB  - The biocompatibility of NiTi shape memory alloys (SMA) has made possible
      applications in self-expandable cardio-vascular stents, stone extraction baskets,
      catheter guide wires and other invasive and minimally invasive biomedical
      devices. The NiTi intermetallic alloy spontaneously forms a thin passive layer of
      TiO(2), which provides its biocompatibility. The oxide layer is thought to form
      as the Ti in the alloy surface reacts with oxygen, resulting in a depletion of Ti
      in the subsurface region - experimental evidence indicates formation of a Ni-rich
      layer below the oxide film. In this paper, we study the initial stages of oxide
      growth on the (110) surface of the NiTi alloy to understand the formation of
      alloy/oxide interface. We initially adsorb atomic and molecular oxygen on the
      (110) surface and then successively add O(2) molecules, up to 2 monolayer of
      O(2). Oxygen adsorption always results in a large energy gain. With atomic
      oxygen, Ti is pulled out of the surface layer leaving behind a Ni-rich subsurface
      region. Molecular O(2), on the other hand adsorbs dissociatively and pulls a Ti
      atom farther out of the surface layer. The addition of further O(2) up to 1
      monolayer is also dissociative and results in complete removal of Ti from the
      initial surface layer. When further O(2) is added up to 2 monolayer, Ti is pulled
      even further out of the surface and a single thin layer of composition O-Ti-O is
      formed. The electronic structure shows that the metallic character of the alloy
      is unaffected by interaction with oxygen and formation of the oxide layer,
      consistent with the oxide layer being a passivant.

PMID- 20144475
TI  - The adhesive properties of coacervated recombinant hybrid mussel adhesive
      proteins.
AB  - Marine mussels attach to substrates using adhesive proteins. It has been
      suggested that complex coacervation (liquid-liquid phase separation via
      concentration) might be involved in the highly condensed and non-water dispersed
      adhesion process of mussel adhesive proteins (MAPs). However, as purified natural
      MAPs are difficult to obtain, it has not been possible to experimentally validate
      the coacervation model. In the present work, we demonstrate complex coacervation
      in a system including recombinant MAPs and hyaluronic acid (HA). Our recombinant
      hybrid MAPs, fp-151 and fp-131, can be produced in large quantities, and are
      readily purified. We observed successful complex coacervation using cationic fp
      151 or fp-131, and an anionic HA partner. Importantly, we found that highly
      condensed complex coacervates significantly increased the bulk adhesive strength
      of MAPs in both dry and wet environments. In addition, oil droplets were
      successfully engulfed using a MAP-based interfacial coacervation process, to form
      microencapsulated particles. Collectively, our results indicate that a complex
      coacervation system based on MAPs shows superior adhesive properties, combined
      with additional valuable features including liquid/liquid phase separation and
      appropriate viscoelasticity. Our microencapsulation system could be useful in the
      development of new adhesive biomaterials, including self-adhesive
      microencapsulated drug carriers, for use in biotechnological and biomedical
      applications.

PMID- 20144476
TI  - The healing of critical-sized femoral segmental bone defects in rabbits using
      baculovirus-engineered mesenchymal stem cells.
AB  - Management of massive segmental bone defects remains a challenging clinical
      problem and bone marrow-derived mesenchymal stem cells (BMSCs) hold promise for
      bone regeneration. To explore whether BMSCs engineered by baculovirus (an
      emerging gene delivery vector) can heal large bone defects, New Zealand White
      (NZW) rabbit BMSCs were transduced with the BMP2-expressing baculovirus or VEGF
      expressing baculovirus, and co-implanted into critical-sized (10mm) femoral
      segmental defects in NZW rabbits. X-ray analysis revealed that the baculovirus
      engineered BMSCs not only bridged the defects at as early as week 2, but also
      healed the defects in 100% of rabbits (13/13) at week 4. The osteogenic
      metabolism, as monitored by positron emission tomography (PET) also suggested the
      completion of bone healing at week 8. When compared with other control groups,
      the BMP2/VEGF-expressing BMSCs remarkably enhanced the segmental bone repair and
      mechanical properties, as evidenced by micro-computed tomography (microCT),
      histochemical staining and biomechanical testing. The ameliorated bone healing
      concurred with the augmented angiogenesis. These data demonstrated, that BMSCs
      engineered to express BMP2 and VEGF accelerate the repair of large femoral bone
      defects and improve the quality of the regenerated bone, which paves an avenue to
      utilizing baculovirus as a vector for BMSCs modification and regenerative
      medicine.

PMID- 20144477
TI  - In vitro evaluation of the long-term stability of polyimide as a material for
      neural implants.
AB  - In order to be used as a material for neural prostheses, polyimide has to
      withstand the body environment over years. To obtain more information about the
      long-term stability of this material, we tested three commercially available
      polyimides (PI2611 - HD-Microsystems (type: BPDA-PPD), U-Varnish-S - UBE (type:
      BPDA-PPD), Durimide 7510 - Fujifilm (type: information not provided)). Specimens
      were stored in phosphate buffered saline (PBS) at 37 degrees C to simulate body
      temperature and at elevated temperatures of 60 degrees C and 85 degrees C to
      accelerate aging. During the course of 20 months, stress-strain curves were
      measured monthly by tensile testing. From these curves the Young's modulus, the
      stress and strain at break, the stress at 10% strain as well as the fracture
      energy were extracted and used to characterize and to statistically evaluate the
      mechanical material properties. Mass loss was determined by weighing polyimide
      foils (Upilex25S - UBE) and optical measurements were conducted to examine
      changes in chemical structure and crystallinity. At 37 degrees C and 60 degrees C
      no change in material behavior could be observed, except for an increase of the
      Young's modulus of the BPDA-PPD type stored at 60 degrees C. This demonstrates
      the long-term stability of all tested polyimides with respect to PBS. All
      extracted quantities mentioned above, as well as the mass, decreased in specimens
      stored in PBS at 85 degrees C. As a comparison, BPDA-PPD type specimens stored at
      85 degrees C in deionized water showed no change in any property but behaved
      similarly to the reference material.

PMID- 20144478
TI  - Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer
      therapy.
AB  - The primary inadequacy of chemotherapeutic drugs is their relative non
      specificity and potential side effects to the healthy tissues. To overcome this,
      drug loaded multifunctional magnetic nanoparticles are conceptualized. We report
      here an aqueous based formulation of glycerol monooleate coated magnetic
      nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high
      payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor
      necrosis factor alpha assay, confocal microscopy. High entrapment efficiency
      approximately 95% and sustained release of encapsulated drugs for more than two
      weeks under in vitro conditions was achieved for different anticancer drugs
      (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not
      affect the magnetization properties of the iron oxide core as confirmed by
      magnetization study. Additionally the MNPs were functionalized with carboxylic
      groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary
      conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO
      MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The
      IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore,
      antibody conjugated GMO-MNPs could be used as potential drug carrier for the
      active therapeutic aspects in cancer therapy.

PMID- 20144479
TI  - Use of vitamin E to protect cross-linked UHMWPE from oxidation.
AB  - Wear and oxidative degradation may limit the life span of UHMWPE implants. Cross
      linking and stabilisation by vitamin E are proposed to overcome wear and
      degradation. The present investigation takes a close look to the oxidative
      behaviour of cross-linked and stabilised UHMWPE. First, the consolidated vitamin
      E stabilised UHMWPE was qualified in terms of microstructure and homogeneity of
      the distribution of the additive to be suitable for oxidation profiles over the
      entire section. Then cross-linked samples with five different concentrations of
      vitamin E (nil to 1.0%) underwent two different ageing protocols. The first was
      under pressurized oxygen at 70 degrees C, as defined in the ASTM F 2003 standard
      with a prolonged period of 60 days, the second was in 5% aqueous hydrogen
      peroxide solution with iron (III) chloride as catalyst at 50 degrees C. The first
      accelerated ageing protocol showed that a vitamin E concentration as low as 0.05%
      is effective to protect irradiated highly cross-linked UHMWPE against oxidation
      when exposed direct to oxygen. Vitamin E stabilised, highly cross-linked UHMWPE
      exhibits therefore no oxidation potential origination from the irradiation
      treatment. Analysis of samples treated by the second chemical ageing yielded,
      that vitamin E is effective to prolong initial stability against a supplementary
      attack of hydrogen peroxide and reactive radicals. The time period of stability
      against the aggressive hydrogen peroxide solution increases with increasing
      vitamin E content. However, even 0.05% have a marked stabilisation effect.
      Therefore, such small additions of vitamin E are effective to protect the UHMWPE
      material against a supplementary exposure to in vivo oxidation after the
      irradiation treatment. In conclusion, vitamin E shields cross-linked UHMWPE for
      orthopaedic application against oxidation in the heat of consolidation, during
      irradiation treatment and finally while implanted in the human body.

PMID- 20144480
TI  - Water-soluble superparamagnetic manganese ferrite nanoparticles for magnetic
      resonance imaging.
AB  - We report here a thermal decomposition approach to the synthesis of water-soluble
      superparamagnetic manganese ferrite (MnFe(2)O(4)) nanoparticles (NPs) for
      magnetic resonance (MR) imaging applications. In this approach, tetraethylene
      glycol was utilized as a coordination and stabilization agent, rendering the NPs
      water-soluble and stable. The formed NPs had a diameter of 7 nm with a narrow
      size distribution, and were superparamagnetic with a saturated magnetization (Ms)
      of 39 emu/g. In vitro cytotoxicity test revealed that the MnFe(2)O(4) NPs were
      biocompatible at a particle concentration below 200 microg/mL. The transverse
      relaxivity of MnFe(2)O(4) NPs in water and cells after incubation were determined
      to be 189.3mm(-1)s(-1) and 36.8mm(-1)s(-1) based on iron concentration,
      respectively. In vivo MR imaging studies in conjunction with inductively coupled
      plasma-atomic emission spectroscopy showed that the MnFe(2)O(4) NPs were
      preferentially accumulated in liver after intravenous injection for 4h. This
      suggests that the developed MnFe(2)O(4) NPs can serve as a sensitive MR imaging
      contrast agent for liver imaging. By appropriately modifying or functionalizing
      the surface of the NPs, these particles may be used for MR detection of other
      diseases.

PMID- 20144481
TI  - Hydrated xenogeneic decellularized tracheal matrix as a scaffold for tracheal
      reconstruction.
AB  - Tracheal injury is a rare but complex problem. Primary tracheal reconstructions
      are commonly performed, but complications such as tension and inadequate vascular
      supply limit the length of surgical resection. The objective of the present study
      was to determine whether a hydrated, decellularized porcine tracheal
      extracellular matrix showed the potential to serve as a functional tracheal
      replacement graft. Porcine tracheas were decellularized and evaluated to
      characterize their biochemical composition and biomechanical behavior. Hydrated
      decellularized tracheal matrix (HDTM) grafts (>5 cm) were implanted
      heterotopically beneath the strap muscle and wrapped in the omentum in a canine
      model for 2 and 8 weeks followed by histologic and mechanical analysis. HDTM
      patches (2 x 3 cm) were also used in a patch tracheoplasty model. The repair site
      was evaluated bronchoscopically and radiographically, and the grafts were
      analyzed by histologic methods to evaluate epithelialization and persistence of
      the cartilage rings. The present study showed that HDTM maintains mechanical
      characteristics necessary for function under physiologic loading conditions even
      after 8 weeks of heterotopic implantation. After orthotopic implantation, the
      grafts were shown to support development of a columnar, pseudostratified,
      ciliated epithelium, but the cartilage structures showed histologic evidence of
      degradation and limited new cartilage formation. The results of the study showed
      tracheal ECM scaffolds support the formation of site-specific epithelium and
      provide sufficient mechanical integrity withstand physiologic pressures in the
      short-term. However, for long-term success, it appears that pre-implantation to
      allow vascularization or preseeding of the graft with chondrocytes will be
      necessary.

PMID- 20144482
TI  - Changes in endovascular trophoblast invasion and spiral artery remodelling at
      term in a transgenic preeclamptic rat model.
AB  - As a follow-up to our previous study which revealed a surprisingly deeper
      endovascular trophoblast (ET) invasion on day 18 in a transgenic preeclamptic
      (PE) rat model (hAngiotensinogen female symbol x hRenin male symbol) compared to
      non-PE controls, we examined further changes in ET invasion and associated spiral
      artery (SA) remodelling at term (day 21). PE transgenic rats and non-PE reversely
      mated (RM) transgenic rats were compared to normal SD rats (C). Sections were
      stained to visualize trophoblast, fibrinoid, vascular smooth muscle (VSM) and
      endothelium. SA were evaluated in three depth levels in the mesometrial triangle
      (MT) using the KS-400 image analysis system. In separate transgenic rats, Doppler
      ultrasound was performed in uterine arteries, and the resistance indices (RI)
      were calculated. Although for the whole MT differences in ET invasion were no
      longer significant between the PE and C, indicating a partial catching up in C
      rats, there was still significantly more ET in the deepest level in the PE group
      as compared to the C and RM groups. At the same time the SA walls in PE rats
      contained significantly more fibrinoid (versus RM and C) and VSM (versus C). In
      all SA cross-sections, re-endothelialisation was prominent, but significantly
      different between PE and C group. The Doppler results showed a significantly
      lower RI in the arcuate uterine artery of the PE group compared to the C group.
      There was no evidence of elimination of deeply invaded ET at term, previously
      considered as a possible mechanism for restriction of vascular remodelling in
      human PE. The differences in vascular remodelling, previously described on day 18
      by histology and Doppler data, were maintained on day 21, but there was extensive
      endothelial repair in the three groups. Atherosis-like lesions were observed in
      the three groups, most frequently in the RM group, but were never associated with
      placental infarcts.

PMID- 20144483
TI  - Lead bioaccumulation in emydid turtles of an urban lake and its relationship to
      shell disease.
AB  - Urban runoff contributes significant amounts of heavy metals into receiving
      waters in which turtles make up a large portion of the biodiversity. Turtles
      accumulate heavy metals in their body and shell bone, yet little is known about
      how it affects their health. Studies in vertebrates have shown bioaccumulation of
      lead to have several deleterious effects such as immunosuppression, impairment of
      skeletal calcification and competition with calcium ion uptake. This study
      surveys the bioaccumulation of lead in emydid turtles of an urban lake and
      investigates the differences based on species, sex, size and its possible
      relationship to shell disease. Shell disease was quantified and small sections of
      shell were collected from each specimen and analyzed for lead content using
      Graphite Furnace Atomic Adsorption Spectrometry. Significant differences of lead
      accumulation were found between species, yet not with sex or body size. Linear
      regression comparison of lead concentration and shell disease showed no positive
      correlation.

PMID- 20144484
TI  - The nature of suicide: science and the self-destructive animal.

PMID- 20144485
TI  - Iatrogenic perinatal pharyngoesophageal injury: a disease of prematurity.
AB  - OBJECTIVE: Perinatal pharyngoesophageal instrumentation, including endotracheal
      intubation, oral suctioning, and feeding tube placement, is often necessary but
      risks tissue damage. Our objective was to estimate the incidence of iatrogenic
      perinatal pharyngoesophageal injury (IPPI) in preterm versus term infants in a
      children's hospital neonatal intensive care unit (NICU). A secondary goal was to
      explore the clinical characteristics and outcomes associated with these
      complications. METHODS: All NICU discharge summaries from 2004 to 2008 were
      searched for IPPI-related keywords. Highlighted records were reviewed and the
      incidence of complications calculated by gestational age and weight. RESULTS: Of
      5910 total NICU discharges, 6 cases of IPPI were identified, for an overall
      incidence of 0.10%. All injuries occurred in infants less than 33 weeks
      gestational age and 1500g, with a trend towards higher incidence with increasing
      prematurity. The incidence of IPPI rose to 4/1321 (0.30%) at 27-32 weeks and
      2/521 (0.38%) at less than 27 weeks gestation. Similarly, IPPI occurred in 3/675
      (0.44%) babies born at 1000-1500g and 3/642 (0.47%) babies below 1000g. All
      affected infants survived with conservative management. CONCLUSIONS: IPPI is a
      rare but serious complication of perinatal airway instrumentation and is
      primarily a disease of prematurity. In this sizeable cohort, no complications
      occurred in term infants, and the incidence of injury increased with decreasing
      gestational age and weight. This increased propensity towards injury should
      prompt special care when performing even routine airway procedures on premature
      neonates.

PMID- 20144486
TI  - Lateral sinus thrombosis: a review of seven cases and proposal of management
      algorithm.

PMID- 20144487
TI  - Minimum-intensity projection of multidetector-row computed tomography for
      assessment of pulmonary hypertension in children with congenital heart disease.
AB  - BACKGROUND: The present study aimed to assess the feasibility of minimum
      intensity projection (minIP) images for the evaluation of pulmonary hypertension
      (PH) in children with congenital heart disease (CHD). METHODS: A total of 70
      consecutive patients (mean age, 4.6 +/- 4.4 years; range, 6 months-16 years)
      underwent multidetector-row computed tomography (MDCT) angiography of the thorax
      prior to cardiac catheterization and lung perfusion scintigraphy. Contiguous
      axial, coronal and sagittal minIP images of 5-mm thickness were reconstructed
      from the contrast-enhanced CT datasets. Two reviewers evaluated the images in
      consensus and qualitatively graded lung parenchyma attenuation as homogeneous
      (Class I), slightly heterogeneous lung attenuation that does not conform to the
      anatomic boundaries of the secondary pulmonary lobule (Class II), and mosaic
      pattern (Class III). MinIP attenuation grading results were then compared with
      those of perfusion scintigraphy. Furthermore, the relationships between the
      results of these modalities and mean pulmonary artery pressure (mPAP) and
      pulmonary vascular resistance (PVR) were evaluated. RESULTS: In 51 (73%)
      patients, concordant findings were observed between the modalities, although
      minIP showed a higher grade for heterogeneous images than did scintigraphy. mPAP
      and PVR showed significant difference among the minIP attenuation classes
      (p<0.0001 for both). High-grade heterogeneous minIP images were associated with
      high mPAP, high PVR, presence of major aortopulmonary collateral artery, and
      chromosomal abnormality. CONCLUSION: MinIP is a promising technique for depicting
      lung perfusion and can be used as superior alternative to scintigraphy in the
      evaluation of PH.

PMID- 20144488
TI  - Glucose control in patients with type 2 diabetes based on frequency of insulin
      glargine administration.
AB  - Glucose control and predictors of a switch from once to twice daily
      administration of insulin glargine in patients with type 2 diabetes was
      investigated. A mean decrease in %A1c of 0.52+/-0.12 (p=0.14) resulted,
      indicating clinical relevance. Daily dose was the only significant predictor of
      twice daily therapy.

PMID- 20144489
TI  - Diminished lipocalin-type prostaglandin D(2) synthase expression in human lung
      tumors.
AB  - Previously, we demonstrated that lipocalin-type prostaglandin D(2) synthase (L
      PGDS) induces apoptosis and prevents cell cycle progression in several cell
      types. In this study we determined the expression of L-PGDS in a variety of human
      lung tumor types. While L-PGDS expression was evident in the surrounding margins,
      we observed significantly decreased protein and gene expression in the tumor
      tissue. Using RT-PCR we demonstrated that L-PGDS gene expression decreased
      proportionately with tumor progression. In addition, we demonstrated that
      exogenously added L-PGDS could suppress the hyperproliferation and PDGF
      stimulated migration of A549 cells, a cultured carcinomic human alveolar basal
      epithelial cell line. We conclude that L-PGDS may play a key role in modulating
      lung cancer growth and may offer a novel diagnostic and therapeutic approach for
      treatment.

PMID- 20144490
TI  - Why is there variation in baseline glucocorticoid levels?

PMID- 20144491
TI  - Qualitative and quantitative analysis of anthraquinone derivatives in rhizomes of
      tissue culture-raised Rheum emodi Wall. plants.
AB  - This paper presents quantification of five anthraquinone derivatives (emodin
      glycoside, chrysophanol glycoside, emodin, chrysophanol and physcion) in rhizomes
      of hardened micro-propagated Rheum emodi plants using high-performance liquid
      chromatography (HPLC). Aseptic shoot cultures were raised using rhizome buds.
      Shoot multiplication occurred in both agar gelled and liquid Murashige and Skoog
      (MS) medium supplemented with 10.0 microM 6-benzylaminopurine (BAP) and 5.0
      microM indole-3-butyric acid (IBA). Rooted plantlets obtained on plant growth
      regulator (PGR)-free medium were transferred to soil with 92% survival. HPLC
      analysis revealed the presence of five anthraquinone derivatives: emodin
      glycoside, chrysophanol glycoside, emodin, chrysophanol and physcion in rhizomes
      of tissue culture-raised plants. Only emodin glycoside (1) and chrysophanol
      glycoside (2) were present in 6-month-old hardened tissue cultured plants. In
      addition, the other three derivatives (emodin (3), chrysophanol (4) and physcion
      (5)) were also detected after 9 months.

PMID- 20144493
TI  - Cost-effectiveness analysis of HLA-B*5701 typing in the prevention of
      hypersensitivity to abacavir in HIV+ patients in Spain.
AB  - INTRODUCTION: Approximately 4% to 8% of patients with HIV-1 treated with abacavir
      present a hypersensitivity reaction (HSR). Various studies have shown a direct
      association between human leukocyte antigen (HLA)-B*5701 and HSR to abacavir. The
      objective of this study was to analyze whether systematic HLA-B*5701 testing to
      prevent HSR in patients treated with abacavir is a cost-effective option for the
      Spanish National Health System. METHODS: An analytical decision-making model was
      constructed as a decision tree model for a simulated cohort of 1000 HIV patients
      to evaluate whether HLA-B*5701 testing to prevent HSR to abacavir was cost
      effective compared with not performing the test. The parameters included in the
      model and the use of healthcare resources should the patient develop HSR were
      taken from the PREDICT-1 study and the opinion of clinical experts. The principal
      result obtained was the incremental cost per HSR avoided. The time horizon of the
      analysis was to 2 months [corrected] . All costs were expressed in 2008 Euros.
      RESULTS: The analysis showed that the total direct healthcare costs per patient
      were ?1344 and ?1322 with and without HLA-B*5701 testing respectively, and that
      36 cases of HSR were prevented per 1000 screened patients. These results yielded
      a cost per HSR avoided of ?630. The sensitivity analysis showed that the results
      were sensitive to the cost of the test, with an economic saving of ?102 or a cost
      effectiveness ratio of ?4234. CONCLUSIONS: The model predicts that generalized
      use of the HLA-B*5701 test before prescribing abacavir in HIV+ patients could
      represent an economic saving or a limited additional cost for the National Health
      System which may be counterbalanced by the benefits in terms of a lower incidence
      of HSR.

PMID- 20144492
TI  - Distinct mechanisms for the impact of distraction and interruption on working
      memory in aging.
AB  - Interference is known to negatively impact the ability to maintain information in
      working memory (WM), an effect that is exacerbated with aging. Here, we explore
      how distinct sources of interference, i.e., distraction (stimuli to-be-ignored)
      and interruption (stimuli requiring attention), differentially influence WM in
      younger and older adults. EEG was recorded while participants engaged in three
      versions of a delayed-recognition task: no interference, a distracting stimulus,
      and an interrupting stimulus presented during WM maintenance. Behaviorally, both
      types of interference negatively impacted WM accuracy in older adults
      significantly more than younger adults (with a larger deficit for interruptions).
      N170 latency measures revealed that the degree of processing both distractors and
      interruptors predicted WM accuracy in both populations. However, while WM
      impairments could be explained by excessive attention to distractors by older
      adults (a suppression deficit), impairment induced by interruption were not
      clearly mediated by age-related increases in attention to interruptors. These
      results suggest that distinct underlying mechanisms mediate the impact of
      different types of external interference on WM in normal aging.

PMID- 20144494
TI  - Synthesis and antimicrobial of new anthraquinone derivatives incorporating
      pyrazole moiety.
AB  - Treatment of 2-cyano-N-(9,10-dioxo-9,10-dihydro-anthracen-2-yl)-acetamide (1)
      with phenyl isothiocyanate/dimethylsulphate afforded the corresponding ketene N,S
      acetal 2 which upon treatment with hydrazine hydrate and 4-aminoantipyrine
      afforded the pyrazolo derivatives 3 and 4, respectively. 3-aminopyrazole
      derivative 3 was utilized as key intermediate for the synthesis of pyrazolo[3,4
      d]pyrimidine 5, pentaaza-as-indacene 6, triaza-cyclopenta[c]phenanthrene 7,
      pyrazolo[1,5-a]pyrimidine 8, 9 and (dimethyl-pyrrol-1-yl)pyrazole 10 derivatives.
      Furthermore, treatment of 1 with DMF/DMA gave the corresponding acrylamide
      derivative 11 which upon treatment with hydrazine hydrate afforded the
      corresponding 3-aminopyrazole derivative 12. Moreover, coupling of 1 with 4,6
      dimethyl-1H-pyrazolo[3,4-b]pyridin-3-diazonium chloride gave the hydrazone
      derivative 13 which upon cyclization with acetic acid afforded the corresponding
      pentaaza-fluorene derivative 14. Representative compounds of the synthesized
      products were evaluated as antimicrobial agents. Some of these compounds
      exhibited promising activities.

PMID- 20144495
TI  - Dialysis research and N-of-1 trials: made for each other?

PMID- 20144496
TI  - Sodium hyaluronate improves outcomes after arthroscopic lysis and lavage in
      patients with Wilkes stage III and IV disease.
AB  - PURPOSE: Among patients with Wilkes stage III and IV disease undergoing
      arthroscopic lysis and lavage, does the use of an intra-articular injection of
      sodium hyaluronate (SH), when compared with Ringer lavage, result in better
      postoperative pain control and temporomandibular joint (TMJ) function? PATIENTS
      AND METHODS: We designed and implemented a randomized, double-blind, pilot
      controlled clinical trial. The study sample was composed of patients with middle
      Wilkes stage (late stage III and early stage IV) disease. Subjects were
      randomized to 1 of 2 treatment limbs. The treatment group received Ringer lactate
      plus an injection of 1 mL of SH after arthroscopy, whereas the control group was
      given Ringer lactate during arthroscopy. The primary outcome variables were pain
      and TMJ function measured by use of visual analog scales. Appropriate descriptive
      and bivariate statistics were computed. A P value less than .05 was considered
      statistically significant. RESULTS: The study sample was composed of 40 patients
      with 20 subjects enrolled in both treatment groups. There were no statistically
      significant differences between the 2 groups in terms of demographics and
      preoperative variables. Postoperative analgesia was statistically significant in
      the treatment group with respect to the control group on the visits on days 14
      and 84. No statistically significant differences were observed between the 2
      groups in the maximum interincisal opening and tolerance. CONCLUSIONS: An intra
      articular injection of SH after arthroscopic lysis and lavage is effective in
      reducing pain in patients with TMJ dysfunction, enhancing postsurgical recovery.
      The analgesic effect of treatment with SH is maintained in the long term.

PMID- 20144497
TI  - Scintigraphic evaluation of osteoblastic activity in extraction sockets treated
      with platelet-rich fibrin.
AB  - PURPOSE: To evaluate the effect of platelet-rich fibrin (PRF) on the early bone
      healing process with bone scintigraphy based on technetium-99m methylene
      diphosphonate uptake in third molar extraction sockets. PATIENTS AND METHODS:
      Fourteen patients with bilaterally soft tissue impacted third mandibular molars
      were included in the study. The right and left impacted third molars were
      surgically extracted in the same session. PRF was randomly administered into one
      of the extraction sockets, whereas the contralateral sockets were left without
      treatment. Four weeks after surgery, scintigrams were obtained to evaluate
      scintigraphic differences between PRF-treated and non-PRF-treated sockets. After
      completion of the clinical study, PRF samples were evaluated by light and
      scanning electron microscopy. RESULTS: The average increase in technetium-99m
      methylene diphosphonate uptake as an indication of enhanced bone healing did not
      differ significantly between PRF-treated and non-PRF-treated sockets 4 weeks
      postoperatively (P > .05). Abundant fibrin and inflammatory cells were observed
      by light microscopic examination of PRF samples. Scanning electron microscopic
      analysis of PRF revealed the existence of platelet aggregates in a fibrin network
      and crystalline particles on the outer surface of PRF. CONCLUSIONS: PRF might not
      lead to enhanced bone healing in soft tissue impacted mandibular third molar
      extraction sockets 4 weeks after surgery. PRF exhibits the potential
      characteristics of an autologous fibrin matrix. However, whether the presence of
      crystal-like particles on the outer surface of PRF alters bone healing should be
      investigated further.

PMID- 20144498
TI  - Frequency of bleeding following invasive dental procedures in patients on low
      molecular-weight heparin therapy.
AB  - PURPOSE: The purpose of this study was to determine the frequency of bleeding
      complications after invasive dental procedures in patients on low-molecular
      weight heparin (LMWH) therapy. MATERIALS AND METHODS: A chart review of patients
      who underwent invasive dental procedures while on LMWH therapy was conducted. The
      following information was obtained: demographics, medical history, social
      history, medications, relevant laboratory values, postoperative bleeding events,
      and use of local hemostatic agents and blood products. RESULTS: Forty-one
      patients (21 men) were identified with 42 dental appointments. The mean age was
      48 years (range, 16 to 78 years). Thirty-seven patients (90%) were on LMWH
      therapy for deep venous thrombosis prophylaxis. Thirty-one patients (76%) were on
      concomitant medications that may potentiate bleeding. Multiple dental extractions
      (range, 2 to 14 teeth) were performed during 19 dental appointments. Twenty-one
      appointments were for single-tooth extraction and 2 were for soft tissue
      biopsies. Three patients (7%) had postextraction bleeding events. All 3 patients
      were on LMWH (enoxaparin) and warfarin therapy concurrently. One patient had
      persistent bleeding after extraction of 4 teeth (international normalized ratio,
      1.6), which was successfully controlled with topical thrombin, administration of
      vitamin K and fresh frozen plasma, and discontinuation of enoxaparin and
      warfarin. Postoperative bleeding in the other 2 patients was managed successfully
      with local hemostatic measures and home care instructions. CONCLUSION: Our study
      suggests that, although postoperative bleeding in patients on LMWH therapy alone
      is rare to nonexistent, patients on warfarin and LMWH may be at increased risk of
      bleeding after invasive dental procedures.

PMID- 20144499
TI  - Osteonecrosis or metastases of the jaw or both? Case report and review of the
      literature.

PMID- 20144500
TI  - Matrix metalloproteinase-9 polymorphism and risk of pelvic organ prolapse in
      Taiwanese women.
AB  - OBJECTIVE: Matrix metalloproteinase-9 is known to play an important role in the
      pathophysiology of pelvic organ prolapse. We investigated whether the matrix
      metalloproteinase-9 gene polymorphisms were associated with pelvic organ prolapse
      by conducting a case-control association study in 92 women with pelvic organ
      prolapse and 152 women without pelvic organ prolapse. STUDY DESIGN: Genotypes of
      the matrix metalloproteinase-9 gene polymorphisms (rs3918242, rs17576, and
      rs2250889) were determined by polymerase chain reaction, followed by restriction
      fragment length polymorphism analysis. RESULTS: There was significant difference
      between women with and without pelvic organ prolapse in the distribution of the
      matrix metalloproteinase-9 rs17576 genotypes evaluated. Using multivariable
      logistic regression, menopausal status, matrix metalloproteinase-9 rs17576
      genotype AG, and matrix metalloproteinase-9 rs17576 genotype GG were
      significantly associated with pelvic organ prolapse. CONCLUSION: The present
      study shows that the polymorphism of matrix metalloproteinase-9 rs17576 may be
      associated with pelvic organ prolapse.

PMID- 20144501
TI  - Role of dissolved organic matters (DOM) in membrane fouling of membrane
      bioreactors for municipal wastewater treatment.
AB  - Two membrane bioreactors (MBRs) with different operation conditions were employed
      to investigate the role of dissolved organic matter (DOM) in membrane fouling.
      DOM characteristics and their correlations with membrane fouling in the MBR
      systems were studied by using three-dimensional excitation-emission matrix (EEM)
      fluorescence technology, gel filtration chromatography (GFC) analysis, and column
      chromatographic method for DOM fractionation, etc. The three-dimensional EEM
      fluorescence spectroscopy analysis indicated that the fluorescence intensity of
      protein-like peaks in DOM samples collected from the MBR zones showed positive
      correlations with membrane fouling. The fluorescence spectra of membrane foulants
      also exhibited two protein-like peaks, confirming that proteins played an
      important role in membrane fouling. The DOM samples collected from MBR zones were
      fractionated into four components, i.e., hydrophobic (HPO), transphilic (TPI),
      charged hydrophilic (HPI-C) and neutral hydrophilic fractions (HPI-N). It was
      found that HPI-N was the most abundant fraction in all the samples, accounting
      for 42.0-48.9% of the total DOM. Test results also showed that HPI-N had the
      highest fouling potential, which could be attributed to the high molecular weight
      (MW) distribution and the high membrane rejection rate of macromolecules.

PMID- 20144502
TI  - Oxidative degradation of dyes in water using Co2+/H2O2 and
      Co2+/peroxymonosulfate.
AB  - Dye degradation using advanced oxidation processes with Co(2+)/H(2)O(2) and
      Co(2+)/peroxymonosulfate (PMS) systems has been investigated. Two types of dyes,
      basic blue 9 and acid red 183, were employed. Several parameters affecting dye
      degradation such as Co(2+), PMS, H(2)O(2), and dye concentrations were
      investigated. The optimal ratio of oxidant (PMS, H(2)O(2))/Co(2+) for the
      degradation of two dyes was determined. It is found that dye decomposition is
      much faster in Co(2+)/PMS system than in Co(2+)/H(2)O(2). For Co(2+)/H(2)O(2), an
      optimal ratio of H(2)O(2) to Co(2+) at 6 is required for the maximum
      decomposition of the dyes. For Co(2+)/PMS, higher concentrations of Co(2+) and
      PMS will increase dye degradation rate with an optimal ratio of 3, achieving 95%
      decolourisation. For basic blue 9, a complete decolourisation can be achieved in
      5 min at 0.13 mM Co(2+), 0.40 mM PMS and 7 mg/l basic blue 9 while the complete
      degradation of acid red 183 will be achieved at 30 min at 0.13 mM Co(2+), 0.40 mM
      PMS and 160 mg/l of acid red 183. The degradation of acid red 183 follows the
      second-order kinetics.

PMID- 20144503
TI  - Decision analysis of emergency ventilation and evacuation strategies against
      suddenly released contaminant indoors by considering the uncertainty of source
      locations.
AB  - In case hazardous contaminants are suddenly released indoors, the prompt and
      proper emergency responses are critical to protect occupants. This paper aims to
      provide a framework for determining the optimal combination of ventilation and
      evacuation strategies by considering the uncertainty of source locations. The
      certainty of source locations is classified as complete certainty, incomplete
      certainty, and complete uncertainty to cover all the possible situations.
      According to this classification, three types of decision analysis models are
      presented. A new concept, efficiency factor of contaminant source (EFCS), is
      incorporated in these models to evaluate the payoffs of the ventilation and
      evacuation strategies. A procedure of decision-making based on these models is
      proposed and demonstrated by numerical studies of one hundred scenarios with ten
      ventilation modes, two evacuation modes, and five source locations. The results
      show that the models can be useful to direct the decision analysis of both the
      ventilation and evacuation strategies. In addition, the certainty of the source
      locations has an important effect on the outcomes of the decision-making.

PMID- 20144504
TI  - Analysis of soil reference materials for vanadium(+5) species by electrothermal
      atomic absorption spectrometry.
AB  - Solid Certified Reference Materials (CRMs) with known vanadium(+5) content are
      currently not commercially available. Because of this, vanadium species have been
      determined in solid CRMs of soil, viz. CRM023-50, CRM024-50, CRM049-50, SQC001
      and SQC0012. These CRMs are certified with only total vanadium content.
      Vanadium(+5) was extracted from soil reference materials with 0.1M Na(2)CO(3).
      The quantification of V(+5) was carried out by electrothermal atomic absorption
      spectrometry (ET-AAS). The concentration of V(+5) in the analyzed CRMs was found
      to be ranging between 3.60 and 86.0 microg g(-1). It was also found that SQC001
      contains approximately 88% of vanadium as V(+5) species. Statistical evaluation
      of the results of the two methods by paired t-test was in good agreement at 95%
      level of confidence.

PMID- 20144506
TI  - A combination of doxycycline and ivermectin is adulticidal in dogs with naturally
      acquired heartworm disease (Dirofilaria immitis).
AB  - Canine heartworm disease is caused by infection with Dirofilaria immitis, a
      filarial nematode that resides in the pulmonary arteries and occasionally in the
      right heart chambers of infected dogs. Here the authors evaluated the effect of a
      combination of doxycycline (10 mg/kg/sid for 30 days) and ivermectin
      pyrantel(6MUg/kg [DOSAGE ERROR CORRECTED] of ivermectin+5mg/kg of pyrantel every
      15 days for 180 days) on microfilariemia, antigenemia and parasite load at
      echocardiography in naturally infected dogs from an endemic region of Italy. Dogs
      were examined monthly for 6 months and followed-up 4 months later. One hundred
      percent of dogs became negative for circulating microfilariae by day 90, while
      8/11 (72.7%) of dogs became antigen-negative by day 300. Of the 7 dogs that were
      positive for visualization of parasites at echocardiography, 6 (85.7%) became
      negative by day 300. Treatment was well-tolerated by all dogs. These results
      suggest that a combination of doxycycline and ivermectin is adulticide in dogs
      with D. immitis.

PMID- 20144507
TI  - Detection of Toxoplasma gondii in lambs via PCR screening and serological follow
      up.
AB  - Toxoplasma gondii in sheep is important as a cause of lambing losses and as a
      food hazard. We aimed to assess the prevalence of infection in lambs via
      development of a standardised PCR technique applied to neonates together with
      follow-up serology at age 4 months. We measured the sensitivity of PCR targeting
      the T. gondii sequences B1, SAG1, 5'SAG2, 3'SAG2 and SAG3 in the presence of
      abundant sheep DNA. B1-PCR was the most sensitive protocol, achieving 50%
      positivity when 0.02 parasite genome copies were present in an assay testing 10
      ng of template. Standardised B1-PCR, and serological follow-up using the modified
      agglutination test (MAT), were used to estimate infection prevalence in lambs
      from two flocks in Northern England. Neonatal prevalence detected by PCR on
      umbilical cord did not differ significantly between viable Charollais (16/243
      (6.6%)) and viable Swaledale (30/264 (11.4%)). In contrast, at age 4 months
      seroprevalence was higher (P<0.001, OR=4.42) in Charollais (50/411 (12.2%)) than
      in Swaledale (10/335 (3.0%)). There was no evidence of a relationship between the
      results of PCR and those of serology. In addition, prenatal exposure was not
      associated with mortality: among non-viable lambs, 3/54 Charollais but 0/16
      Swaledale were PCR positive, and 1/26 Charollais and 1/14 Swaledale were
      seropositive. These results indicate that both standardised B1-PCR, and serology,
      can be used to detect T. gondii in lambs. Frequent prenatal exposure was detected
      without mortality and sometimes without an IgG response. Some lambs, without PCR
      evidence of prenatal exposure, seroconverted early.

PMID- 20144508
TI  - A recombinant DNA vaccine encoding Eimeria acervulina cSZ-2 induces immunity
      against experimental E. tenella infection.
AB  - The study describes vaccination experiments with highly immunogenic sporozoite
      Eimeria acervulina cSZ-2 to determine its efficacy against E. tenella challenge.
      Chickens were randomly divided into six groups. The chickens in the vaccinated
      groups were vaccinated with pVAX1-cSZ2, pVAX1-IL-2 and pVAX1-cSZ2-IL-2 twice 'at
      days 14 and 21' with dose rate of 100microg intramuscularly. At 28 days of age,
      all chickens except the non-vaccinated non-challenged control group were
      inoculated orally with 5x10(4) sporulated oocysts of E. tenella. Seven days
      later, all chickens were weighed and slaughtered for caecum examination. Our
      findings make it obvious that cSZ-2 DNA immunisation can induce host immune
      responses by decreasing intestinal lesions, body weight loss and oocyst ratio,
      imparting partial protection. It is concluded that co-administration of
      interleukin 2 can further enhance its immunity, leading towards further research.

PMID- 20144510
TI  - Addictive potential: A=E/T(max)xt(1/2).
AB  - This hypothesis named Salerian Addictive Potential (SAP) suggests that the
      addictive potency of any substance may be calculated with an algebraic equation
      of A=E/T(max)xt(1/2), where A is the addictive potency, E represents the euphoric
      potency, T(max) is the time to reach peak plasma concentration, and t(1/2) is the
      plasma elimination half-life. This review offers medical evidence to suggest
      there is a negative association between the addictive potency of a substance and
      T(max) and t(1/2), whereas the euphoric potency of a substance increases its
      addictive potency. SAP seems incompatible with the current FDA and government
      sponsored schedule for classification of addictive substances.

PMID- 20144509
TI  - Marital behavior, oxytocin, vasopressin, and wound healing.
AB  - Animal studies have implicated oxytocin and vasopressin in social bonding,
      physiological stress responses, and wound healing. In humans, endogenous oxytocin
      and vasopressin levels covary with perceptions of relationship quality, marital
      behaviors, and physiological stress responses. To investigate relationships among
      marital behavior, oxytocin, vasopressin, and wound healing, and to determine the
      characteristics of individuals with the highest neuropeptide levels, 37 couples
      were admitted for a 24-h visit in a hospital research unit. After small blister
      wounds were created on their forearm, couples participated in a structured social
      support interaction task. Blister sites were monitored daily following discharge
      to assess wound repair speed. Blood samples were collected for oxytocin,
      vasopressin, and cytokine analyses. Higher oxytocin levels were associated with
      more positive communication behaviors during the structured interaction task.
      Furthermore, individuals in the upper oxytocin quartile healed blister wounds
      faster than participants in lower oxytocin quartiles. Higher vasopressin levels
      were related to fewer negative communication behaviors and greater tumor necrosis
      factor-alpha production. Moreover, women in the upper vasopressin quartile healed
      the experimental wounds faster than the remainder of the sample. These data
      confirm and extend prior evidence implicating oxytocin and vasopressin in
      couples' positive and negative communication behaviors, and also provide further
      evidence of their role in an important health outcome, wound healing.

PMID- 20144511
TI  - [Liver transplantation and pregnancy].
AB  - Management during their sexual life of patients with a liver transplantation is a
      more or less common situation depending centers. Based on literature review, a
      focus on management of recipient women was conducted, from contraception to
      pregnancy, describing the complications related to the status of transplant
      recipient, but also those that may be related to immunosuppressive agents. If
      fertility and access to contraception are only slightly modified by graft,
      complications related to graft or immunosuppressive drugs can affect the
      pregnancy. On the maternal side, hypertension and preeclampsia are more common,
      as well as renal dysfunction, iatrogenic diabetes and bacterial or viral
      infections, acute rejection and graft loss do not appear to be influenced by
      pregnancy. The fetus is also exposed to risks such as induced prematurity and
      IUGR. Pregnancy in recipients of hepatic grafts therefore requires joint follow
      up by transplant specialist and perinatologist, which leads in most cases to
      successful outcome for mother and child.

PMID- 20144512
TI  - [Maturity-onset-diabetes-of-the young-5 and genital malformations diagnostic
      management: case report].
AB  - With an incidence of 5% in the female population, genital malformations are a
      frequent clinical occurrence presented by Oppelt et al. (2007) [1]. First, we
      have to diagnostic them and search for extra genital malformation when it is
      necessary. Think about maturity-onset-diabetes-of-the young 5 (MODY-5) when
      there's a personnel or family story of diabetes. This is often within the
      competence of the diabetologist and our speciality can be put in contribution in
      the research for the associated genital malformation. We report on the case of a
      young woman age of 19 with diabetes diagnosed during her adolescence, a
      nephropathy with polycystic kidneys, biological cytolysis, a bicornuate
      unicervical uterus while this may be a clinical diabetes MODY-5 confirmed by the
      discovery of the complete deletion of the gene coding for HNF-1 beta in the
      heterozygous state.

PMID- 20144513
TI  - Serial passage of the etiologic agent of epizootic bovine abortion in
      immunodeficient mice.
AB  - Molecular studies have provided convincing evidence that a unique
      deltaproteobacterium is the causative agent of epizootic bovine abortion (EBA).
      Bovine fetuses, infected following dam exposure, are the only identified
      susceptible mammalian host. The inability to cultivate the bacterial agent of EBA
      (aoEBA) in vitro, associated with the substantial cost of bovine experimentation,
      drove efforts to identify an alternative laboratory animal host. Mice with severe
      combined immunodeficiency (SCID) were chosen as a potential host after
      immunocompetent mice proved resistant to infection. SCID mice inoculated with
      aoEBA-infected bovine fetal thymus homogenates began to show clinical signs at 2
      months and became increasingly cachectic over the next 1-2 months. Following a
      2nd passage (P2) through SCID mice, three susceptible pregnant heifers were
      inoculated with P2 murine tissue homogenates. All three fetuses presented with
      lesions indistinguishable from naturally occurring EBA, confirming successful
      passage of the bacterial pathogen in SCID mice. All murine (P1 and P2) and bovine
      fetal tissues contained aoEBA as determined by PCR; 16S bacterial ribosomal
      nucleotide sequences were identical in all murine and fetal bovine tissues
      examined. Bacteria in fetal bovine tissues were determined to be heavily
      opsonized, based upon microscopic evaluation of tissues stained with either FITC
      conjugated anti-bovine IgG or biotin-conjugated anti-bovine IgG in conjunction
      with avidin-FITC. Unlike the near-term bovine fetus, the absence of an antibody
      response in infected SCID mice permits harvest of unopsonized bacteria for
      development of serologic assays.

PMID- 20144514
TI  - Prevalence of Capnocytophaga canimorsus and Capnocytophaga cynodegmi in dogs and
      cats determined by using a newly established species-specific PCR.
AB  - Capnocytophagacanimorsus and Capnocytophagacynodegmi, fastidious gram-negative
      rods, are commensal microbes thriving in the oral cavities of dogs and cats. C.
      canimorsus can sometimes cause fatal systemic infections in humans. In the
      present study, we established a specific PCR which could identify and distinguish
      C. canimorsus from C. cynodegmi. The prevalence of Capnocytophaga spp. in dogs
      and cats was determined using this method. C. canimorsus was detected in 74% of
      dogs and 57% of cats. C. cynodegmi was detected in 86% of dogs and 84% of cats.
      The prevalence of Capnocytophaga spp. obtained in this study is somewhat higher
      than those reported previously where bacterial isolation method was used for
      identification. This is probably due to the fact that the PCR detection is more
      sensitive compared to bacterial isolation. Our findings suggest the importance of
      informing people who belong to high-risk groups as well as health care workers on
      C. canimorsus infection and its potential risk to people particularly to those
      who are immunocompromised.

PMID- 20144515
TI  - A quick discrimination of vegetable oil by solid-phase microextraction method.
AB  - A trace amount of vegetable oil was picked up with solid-phase microextraction
      (SPME) fiber and identified using a gas chromatograph-mass spectrometer (GC-MS).
      Unsaponifiable constituents such as sterols could be detected by an injection of
      the SPME fiber, with the fiber touching the vegetable oil and then leading
      directly into the port of the GC-MS. After thermal desorption of unsaponifiable
      constituents, the remaining triacylglycerols or oil that was freshly added to the
      fiber were recovered with a little organic solvent, and the profiles of the fatty
      acids that had been constructing the acylglycerols were determined using a base
      catalyzed trans-esterification method which produced fatty acid methyl esters.
      The simple and rapid techniques that make up this method make it possible to
      significantly reduce the preparation time and as well as the required sample
      volume. When urgent discrimination is required with high accuracy, this technique
      could serve as a useful and powerful tool for identification of vegetable oil.

PMID- 20144516
TI  - Improvement of intractable childhood epilepsy following acute viral infection.
AB  - In this study, we report 11 patients with intractable childhood epilepsy that
      improved following acute viral infection. The patients were 8 boys and 3 girls.
      Six of the 11 children were diagnosed as West syndrome (5 of the symptomatic type
      and 1 of the cryptogenic type). The remaining 5 children were myoclonic seizures.
      The patients became seizure free within 6 days following acute viral infections
      without an exchange or addition of antiepileptic drugs (AEDs). The types of acute
      viral infections were Exanthema subitum (Roseola infantum) in 5 patients,
      Rotavirus gastroenteritis in 2 patients, Measles infection in 2 patients,
      Herpetic stomatitis in 1 patient and Common cold in the remaining patient. Salaam
      seizures and/or tonic spasms disappeared within 6 days after the onset of viral
      infections, and hypsarrhythmia evolved to localized spikes on
      electroencephalography (EEG) in the patients with West syndrome. Epileptic
      seizures disappeared rapidly and EEG gradually normalized or improved in patients
      with myoclonic seizures. Four patients became seizure free for 5 years to 20
      years. In 6 patients, seizures relapsed within 14 days to 1 month after the
      disappearance of seizures. One child remained seizure free for 12 months after
      viral infection. Common factors in 4 children who were continuously seizure free
      include (1) normal or almost normal findings of brain CT/MRI, (2) normal
      development prior to the onset of epileptic seizures, and (3) a short time
      interval between the onset of seizures and the acute viral infection. We propose
      several hypotheses including an immunological effect for the improvement of
      intractable childhood epilepsy following acute viral infection. Further study may
      provide important information concerning the mechanism of seizure control and the
      applicable to treatment for intractable childhood epilepsy.

PMID- 20144517
TI  - Detection of intracranial aneurysms using three-dimensional multidetector-row CT
      angiography: is bone subtraction necessary?
AB  - PURPOSE: The aim of this study was to evaluate the usefulness of three
      dimensional CT angiography (3D CTA) with bone subtraction in a comparison with 3D
      CTA without bone subtraction for the detection of intracranial aneurysms.
      MATERIALS AND METHODS: Among 337 consecutive patients who had intracranial
      aneurysms detected on 3D CTA, 170 patients who underwent digital subtraction
      angiography (DSA) were included in the study. CTA was performed with a 16-slice
      multidetector-row CT (MDCT) scanner. We created the 3D reconstruction images with
      and without bone subtraction by using the volume rendering technique. Three
      neuroradiologists in a blinded fashion interpreted both 3D CTA images with and
      without bone subtraction. The diagnostic accuracy of both techniques was
      evaluated using the alternative free-response receiver operating characteristic
      (ROC) analysis. The sensitivity and positive predictive value were also
      evaluated. RESULTS: A total of 200 aneurysms (size: 2-23 mm) were detected in 170
      patients. The area under the receiver operating characteristic curve (Az) for 3D
      CTA with bone subtraction (mean, Az=0.933) was significantly higher than that for
      3D CTA without bone subtraction (mean, Az=0.879) for all observers (P<0.05). The
      sensitivity of 3D CTA with bone subtraction for three observers was 90.0, 92.0
      and 92.5%, respectively, while the sensitivity of 3D CTA without bone subtraction
      was 83.5, 83.5 and 87.5%, respectively. No significant difference in positive
      predictive value was observed between the two modalities. CONCLUSIONS: 3D CTA
      with bone subtraction showed significantly higher diagnostic accuracy for the
      detection of intracranial aneurysms as compared to 3D CTA without bone
      subtraction.

PMID- 20144519
TI  - Chemical pattern-aided classification to simplify the intricacy of morphological
      taxonomy of Epimedium species using chromatographic fingerprinting.
AB  - Epimedium herb (Yinyanghuo), one of the popular Chinese materia medica, is a
      multiple species colony of Epimedium genus belonging to Berberidaceae. There are
      five species of Epimedium that have been officially adopted in Chinese
      Pharmacopoeia under the same crude drug name 'Yinyanghuo' comprising Epimedium
      brevicornu, E. koreanum, E. sagittatum, E. pubescens, and E. wushanense. In
      addition, non-official species like E. acuminatum, E. miryanthum and E.
      leptorrhizum are also mix-used. Frequently, the morphological taxonomical
      identification is very difficult during on-site inspection for species
      authentication in the market. Researchers are often bewildered by the multiple
      species ambiguity when putting this crude drug in use. Referring to the bioactive
      constituents that are vital for therapeutic efficacy, the key to clarifying the
      multiple species confusion should rely on analysis of the bioactive composition.
      It is well known that medicinal Epimedium herbs contain special C-8 prenylated
      flavonol glycosides which contribute to various bioactivities and the major four,
      epimedin A (A), epimedin B (B), epimedin C (C) and icariin (I), are unanimously
      used as bioactive markers for quality control. In this study, HPLC-DAD
      fingerprinting was performed for investigating the molecular spectrum of various
      Epimedium species. It was found that the four major flavonoids constitute the
      middle part of the chromatographic profiles to form a specific region (named as
      'ABCI fingerprint region') being dominant in the HPLC profiles of all medicinal
      Epimedium species, and the five official species express five different 'ABCI'
      patterns (different peak: peak ratios). Our study found that the convergent
      tendency of the 'ABCI region' among multiple species of Epimedium could
      facilitate differentiation of complex commercial samples based on similar
      bioactive composition should confer similar bioactivities. Merging the different
      species that possess the same 'ABCI region' pattern into the same group can
      create a simpler bioactive-fraction-aided classification array by clustering the
      commercial samples into three bioactive ingredients-based fingerprint patterns -
      'E.b. pattern', 'E.k. pattern' and 'extensive E.w. pattern'. This approach offers
      the feasibility of characterizing and quality-controlling complex samples in the
      same genus designated under a single herbal drug entity on the premise of
      possessing the same bioactive ingredients pattern and supported by long-term
      traditional usage.

PMID- 20144518
TI  - Direct quantitation of glucoraphanin in dog and rat plasma by LC-MS/MS.
AB  - A rapid method to quantify levels of the beta-thioglycoside N-hydroxyl sulfate,
      glucoraphanin, in dog and rat plasma to support pre-clinical toxicological and
      pharmacological studies has been developed using liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). Glucoraphanin was extracted from plasma by protein
      precipitation with acetonitrile and separated via hydrophilic interaction liquid
      chromatography (HILIC) using a Luna 5microm Silica (2) 100A column (50mmx2.0mm)
      at a flow rate of 0.3mL/min. Solvent A consisted of 200mM ammonium acetate and
      formic acid (99:1, v/v) and Solvent B was acetonitrile. Initial conditions (90%
      Solvent B) were held for 0.01min after injection, decreased to 40% in 0.5min and
      held constant for 2.5min, returning to initial conditions for 3min
      (reequilibration time). Glucoraphanin was detected by MS/MS using a turbo ion
      spray interface as the ion source operating in negative ion mode. Acquisition was
      performed in multiple reaction monitoring mode at m/z 435.8-->96.7. The method
      was validated for the calibration range 10-2000ng/mL. Within- and between-run
      precision for the low, mid and high QC levels was 8% R.S.D. or less and accuracy
      ranged from 100 to 113%. The lower limit of quantification was 10ng/mL;
      calibration curves encompassed the range of plasma concentrations expected to be
      found in bioavailability and pharmacokinetics studies with glucoraphanin. The
      method has successfully been applied to the determination of glucoraphanin in dog
      and rat plasma and should be extendable to other species as well.

PMID- 20144520
TI  - Isolated adrenal hematoma presenting as acute right upper quadrant pain.
AB  - BACKGROUND: Adrenal hematoma is an infrequent occurrence in the setting of adult
      trauma care. It is typically associated with diffuse abdominal injury, and its
      presence is commonly correlated with high injury severity and mortality.
      OBJECTIVES: To discuss the recognition of adrenal hematoma as a cause of right
      upper quadrant pain. CASE REPORT: We present the case of a 23-year-old man who
      presented to the Emergency Department (ED) with acute right upper quadrant pain
      after blunt trauma to the area; he was initially diagnosed with an abdominal
      contusion with an incidental adrenal adenoma. After experiencing continued pain
      for 2 days, the patient returned to the ED for re-evaluation. Subsequent imaging
      revealed that the adrenal mass had enlarged, and it was determined that this
      patient had suffered an acute adrenal hematoma. The lesion was determined to be
      self-limited and the patient was treated with supportive care. Follow-up images 8
      weeks later revealed resolution of the hematoma and the patient reported complete
      resolution of symptoms. We also discuss adrenal hematoma in the trauma setting
      and explain that in our patient, given the clinical scenario and statistical
      evidence, an initial diagnosis of adrenal hematoma should be favored over
      abdominal contusion with incidental adenoma. CONCLUSION: We describe a case of a
      traumatic isolated adrenal hematoma that presents acutely as right upper quadrant
      pain. This unusual presentation highlights the need for recognition of the
      adrenal gland as a potential cause of right upper quadrant pain in the trauma
      setting.

PMID- 20144521
TI  - Coping with infertility online: an examination of self-help mechanisms in an
      online infertility support group.
AB  - OBJECTIVE: To examine communication within an online infertility support group.
      METHODS: A content analysis of 3500 messages posted to infertility bulletin
      boards. RESULTS: The most frequently used self-help mechanisms were support or
      empathy (45.5%) and sharing personal experiences (45.4%), followed by the
      provision of information and advice (15.9%), gratitude (12.5%), friendship
      (9.9%), chit-chat (9.4%), requests for information or advice (6.8%) and
      universality (4.8%), with negative statements (0.3%) and creative expressions
      (0.2%) being the least frequent categories. CONCLUSION: These findings suggest
      that online support groups can provide a viable alternative source of support for
      couples dealing with infertility. PRACTICE IMPLICATIONS: Health care
      professionals interested in developing online support interventions should look
      to tailor support resources to the specific needs of patients at different stages
      of the infertility journey.

PMID- 20144522
TI  - Outcome of parent-physician communication skills training for pediatric
      residents.
AB  - OBJECTIVE: communication skills represent an essential component of clinical
      competence. In the field of pediatrics, communication between physicians and
      patients' parents is characterized by particular difficulties. To investigate the
      effects of a parent-physician communication skills training program on OSCE
      performance and self-efficacy in a group control design. METHODS: parallel to
      their daily work in the outpatient department, intervention-group experienced
      clinicians in practice (n=14) participated in a communication training with
      standardized parents. Control-group physicians (n=14) did not receive any
      training beyond their daily work. Performance was assessed by independent video
      ratings of an OSCE. Both groups rated their self-efficacy prior to and following
      training. RESULTS: regarding OSCE performance, the intervention group
      demonstrated superior skills in building relationships with parents (p<.024) and
      tended to perform better in exploring parents' problems (p<.081). The
      communication training program led to significant improvement in self-efficacy
      with respect to the specific training objectives in the intervention group
      (p<.046). CONCLUSION: even in physicians with considerable experience, structured
      communication training with standardized parents leads to significant improvement
      in OSCE performance and self-efficacy. PRACTISE IMPLICATIONS: briefness and tight
      structure make the presented communication training program applicable even for
      experienced physicians in daily clinical practice.

PMID- 20144523
TI  - The physical examination in telecardiology and televascular consultations: a
      study using conversation analysis.
AB  - OBJECTIVE: This paper describes communication in the physical examination phases
      of telemedicine consultations. METHODS: Using the method of conversation
      analysis, we draw on 10 telemedicine consultations (five telecardiology and five
      televascular) between primary and tertiary care in the UK. RESULTS: Physical
      examination is absent in telecardiology consultations. In televascular
      consultations the professionals try to compensate for the lack of physical
      proximity by getting involved in a form of collaboration that constitutes a novel
      environment for all. Separated from the patient by physical space, the specialist
      orchestrates the positioning of the patient, the camera and the primary care
      nurse's activity via the use of a video-link. CONCLUSION: Telemedicine offers
      primary care nurses a unique opportunity to engage in active collaboration with
      hospital specialists. The nurses' examination skills are recruited because
      physical examination is conducted from distance and the specialist cannot touch
      the patient or see parts of the body with ease. We speculate that difficulties
      with the physical examination may have contributed to the relatively slow
      adoption of telemedicine. PRACTICE IMPLICATIONS: The analysis reveals some new
      communication practices that participants in telemedicine are called to adopt.
      This can be used to inform training interventions that focus both on patient and
      professional.

PMID- 20144524
TI  - Metacognition, memory disorganization and rumination in posttraumatic stress
      symptoms.
AB  - The present study aimed to assess the relative contribution of memory
      disorganization and beliefs about trauma memory in the prediction of
      posttraumatic stress symptoms. A sample of 95 student nurses and midwives
      narrated their memory of the most distressing placement related event they had
      experienced. Several questionnaires were administered, including the Beliefs
      about Memory Questionnaire (BAMQ), which was devised for the study. Pearson's
      correlations, hierarchical analyses and mediation analyses were performed on the
      data. The reliability and validity of the BAMQ gained preliminary support.
      Beliefs about the trauma memory, but not memory disorganization within the trauma
      narrative, predicted a significant proportion of the variance in posttraumatic
      stress symptoms after control variables were accounted for. Consistent with the
      metacognitive model of PTSD, the use of rumination mediated the relationship
      between beliefs about the trauma memory and PTSD symptoms. The findings provide
      preliminary support for the role of meta-memory in the maintenance of PTSD
      symptoms and question the importance of memory disorganization.

PMID- 20144525
TI  - Endovascular treatment of late "endoleak" following open surgical repair using
      bypass and exclusion aneurysm repair.
AB  - BACKGROUND: We sought to present endovascular management options of persistent or
      recurrent aneurysm sac flow ("endoleak") after operative retroperitoneal
      exclusion of infrarenal abdominal aortic aneurysm (AAA). METHODS: Recurrent or
      persistent aneurysm perfusion was diagnosed in three patients primarily treated
      with aneurysm exclusion and bypass. The medical history, course of disease, and
      surgical management of these patients were reviewed. RESULTS: Three patients
      primarily treated for infrarenal AAA by division of the aorta with suture closure
      of the proximal aneurysm end, ligation of the outflow vessels, and bypass of the
      excluded aortoiliac segment presented with persistent or recurrent AAA sac
      perfusion and growth. The feeding vessels were the iliac arteries in all cases.
      Endovascular repair using coil embolization and/or deployment of an occluder or
      stent-graft was successful in all patients with a follow-up of 42, 36, and 30,
      months respectively. CONCLUSION: Open AAA repair using the exclusion and bypass
      technique is associated with the risk of persistent perfusion or reperfusion of
      the aneurysm sac, which is similar to an endoleak after endovascular aortic
      aneurysm exclusion. Endovascular therapy should be considered as first-choice
      treatment when feasible.

PMID- 20144526
TI  - Use of a Viabahn stent for repair of a common carotid artery pseudoaneurysm and
      dissection.
AB  - Carotid procedures in the previously operated neck are both technically demanding
      and subject to increased rates of complications. Adding radiation to the operated
      field only increases these risks. The incidence of cranial nerve injury in the
      reoperative neck has increased. Similarly, patients with a history of radiation
      are at increased risk for stroke, cranial nerve injury, and wound complications.
      Before the endovascular era, the only option for repair of an extracranial
      carotid aneurysm was open operation. Recently, more experience has been gained
      using endovascular techniques to repair these aneurysms. We present a patient
      with a history of radiation and radical neck dissection who developed a
      pseudoaneurysm of the common carotid artery. This pseudoaneurysm was repaired
      successfully using a Viabhan covered stent graft.

PMID- 20144527
TI  - Historical overview of varicose vein surgery.
AB  - Varicose veins are as old as Hippocrates. Varicose vein treatments come and go.
      Surgery for varicose vein disease is one of the commonest elective general
      surgical procedures. The history of varicose vein surgery has been traced. We
      note the first descriptions of varicose veins, and we particularly focus on the
      ligation of the saphenofemoral junction, stripping of the great saphenous veins,
      phlebectomy, and perforant vein surgery. We end with the rapid rise of minimally
      invasive procedures, such as foam sclerotherapy, radiofrequency ablation, and
      endovenous lasertherapy. Within 10 years, the advantages of minimal invasiveness
      for these procedures, combined with claims of equivalent short-term outcomes and
      even better long-term results, have already influenced our everyday practice. At
      present, the gold standard treatment of varicose veins still is surgical ligation
      and stripping of the insufficient vein. Concomitantly or sequentially with the
      treatment of truncal insufficiency, residual varicosities can be treated by
      phlebectomy. New minimally invasive techniques, however, have changed the
      clinical landscape for varicose vein surgery tremendously. The dramatic changes
      of the last decade are probably the precursors of the next generation.

PMID- 20144528
TI  - Bifurcated abdominal aortic endograft deployment via the carotid artery.
AB  - BACKGROUND: We report the use of the common carotid artery as an alternate access
      in endovascular therapy. METHODS/RESULTS: A 77-year-old man with an enlarging
      abdominal aortic aneurysm in whom previous attempts at standard endovascular
      repair had failed because of difficult iliac access underwent endovascular repair
      via the left common carotid artery. A custom-made Zenith infrarenal bifurcated
      stent graft was reverse-loaded on a thoracic distal delivery device and deployed
      in a caudal-to-cranial fashion. The patient made an uneventful recovery without
      any complications. Computed tomography confirmed exclusion of the aneurysm.
      CONCLUSION: This case report highlights the role of the common carotid artery as
      an access vessel for stent-graft deployment when standard access via the femoral
      and iliac routes is unachievable.

PMID- 20144529
TI  - Intraoperative duplex and functional popliteal entrapment syndrome: strategy for
      effective treatment.
AB  - Functional popliteal entrapment syndrome (FPES) was first described by Rignault
      and colleagues in 1985 (Int. Angiol. 1985;4:341-343). This syndrome results from
      compression of the popliteal artery by a hypertrophied medial head of the
      gastrocnemius muscle with no other identifiable anatomical abnormality. The
      incidence, significance, natural history, and appropriate treatment of this
      syndrome remain controversial. We present three cases of FPES where
      intraoperative positional duplex scans guided gastrocnemius muscle resection and
      confirmed appropriate resection. Additionally, B-mode duplex obtained during one
      of the cases demonstrated intimal changes consistent with repetitive vessel
      trauma. All patients had resolution of their claudication and normal
      physiological testing postoperatively.

PMID- 20144530
TI  - Use of Wall stent to exclude a thrombosed inferior vena cava filter.
AB  - The use of inferior vena cava (IVC) filters has increased dramatically over the
      last two decades. Thrombosis of the IVC is a potentially catastrophic
      complication of caval filter placement, and its reported incidence ranges 3.6
      11.2%, depending on filter type. We present a 69-year-old female with a history
      of deep vein thrombosis of the right leg. Prior to a planned spinal operation, a
      Gunther Tulip filter was placed (Cook Medical, Bloomington, IN). Postoperatively,
      the patient developed bilateral iliofemoral thrombosis that extended into the IVC
      filter. Several weeks passed, and after unsuccessful attempts at recanalization
      in the community setting, the patient was referred to our group for treatment.
      After an unsuccessful attempt at balloon angioplasty, two 10 x 60mm Protege GPS
      stents (EV3, Plymouth, MN) were deployed in the common femoral, external, and
      internal iliac veins bilaterally. After an unsuccessful attempt at retrieval, the
      Tulip filter was excluded from the IVC using a 16 x 60mm Wall Stent (Boston
      Scientific, Natick, MA). Unobstructed flow was now noted from the femoral system
      all the way through the superior vena cava. The patient experienced immediate
      relief of her symptoms.

PMID- 20144531
TI  - Bifurcated endograft repair of ilio-iliac arteriovenous fistula secondary to
      lumbar diskectomy.
AB  - Ilio-iliac arteriovenous (AV) fistula is a rare complication after lumbar
      diskectomy. Endovascular repair of such fistulas is a growing trend in vascular
      surgery. This is a case report of an endovascular exclusion of an ilio-iliac AV
      fistula in a 51-year-old male. This man presented with high-output congestive
      heart failure and ascites. The AV fistula was discovered 17 years after a lumbar
      diskectomy. Computed topography (CT) revealed a right common iliac artery
      pseudoaneurysm connecting to the left common iliac vein. The fistula was repaired
      using a bifurcated Gore Excluder endograft. There were follow-up CT scans at 6
      and 10 months confirming exclusion of the AV fistula. Endovascular AV fistula
      repair offers a safe, effective method for managing ilio-iliac AV fistulas.

PMID- 20144532
TI  - An 18-cm-large renal arteriovenous fistula treated by nephrectomy.
AB  - Idiopathic renal arteriovenous fistulas are extremely rare. They are believed to
      occur as the result of congenital renal artery aneurysm that erodes into an
      adjacent vein. We report a case of a 48-year-old man in whom we discovered
      fortuitously a painless mass of the right flank. Computed tomography revealed a
      huge renal artery aneurysm with giant arteriovenous fistula in the absence of any
      clinical stigmata. Given the size of the fistula and the partial destruction of
      the renal parenchyma, nephrectomy was successfully performed.

PMID- 20144533
TI  - Analysis of calcifications in patients with coral reef aorta.
AB  - BACKGROUND: Coral reef aorta is a rare vascular disease with intraluminal
      calcifications of the dorsal part of the visceral aorta. The pathogenesis of this
      disease with its topographic and morphologic characteristics is unknown. The aim
      of our study was to investigate calcification inhibitors and the ultrastructure
      of calcifications in patients with coral reef aorta. METHODS: Ten patients with
      coral reef aorta were examined. Calcified specimens were investigated by
      immunohistochemical techniques for the expression of the calcification inhibitors
      matrix gla protein (MGP) and fetuin-A. Vessel walls were also assessed by
      electron microscopic techniques including electron energy-lost spectroscopy,
      electron dispersive spectroscopy, and electron diffraction. Sera of patients were
      analyzed for fetuin-A, uncarboxylated MGP (ucMGP), and osteoprotegerin. RESULTS:
      As assessed by immunohistochemistry, most MGP was detected in the vicinity of
      calcified regions. Serum levels of the calcification inhibitors ucMGP, fetuin-A,
      and osteoprotegerin were 370+/-107 nmol/L, 0.57+/-0.03 g/L, and 5.64+/-0.79
      pmol/L, respectively. Ultrastructural analysis of calcified specimens showed a
      core-shell structure with multiple calcification nuclei. Calcifications displayed
      a fine-crystalline character, and elemental analysis revealed hydroxyl apatite as
      the chemical compound. CONCLUSION: The coral reef aorta represents an extreme
      exophytic growth of vascular calcification with multiple nuclei which resemble
      typical media calcification. Positive vascular immunostaining and low serum
      levels of both fetuin-A and ucMGP suggest a pathophysiologic role of these
      calcification inhibitors in the development of coral reef aorta.

PMID- 20144534
TI  - Isolated atherosclerotic aneurysm of the profunda femoris artery.
AB  - True aneurysms of the profunda femoris artery are extremely rare in comparison to
      pseudoaneurysms of the same artery. In most cases they are accompanied by
      aneurysms of the abdominal aorta or peripheral vessels. The most common reason
      for aneurysmic dilatation of vessels is a generalized vascular degenerative
      process. An isolated true aneurysm of the profunda femoris artery due to
      atherosclerosis is markedly unusual. These aneurysms have a high incidence of
      complication; therefore surgical management is mandatory for all diagnosed cases
      regardless of whether they are symptomatic or not. We describe a case of a 73
      year-old man with a large isolated atherosclerotic aneurysm of the profunda
      femoris artery. He presented with an enlarging, progressively debilitating mass
      in his upper thigh. Ultrasound and computed tomography-angiography demonstrated a
      15 x 14 cm large aneurysm of the profunda femoris artery. The patient was
      successfully treated by aneurysm neck ligation and sac decompression.

PMID- 20144535
TI  - Laparoscopic resection of retroperitoneal schwannoma near the inferior vena.
AB  - BACKGROUND: Schwannomas are usually benign tumors that arise from the schwann
      cells in the neural sheaths of peripheral nerves. Most schwannomas occur in the
      head, neck, or limbs and rarely in the retroperitoneal space. In the
      retroperitoneal space, schwannomas are most commonly located near the adrenal
      gland. We report a successfully resected retroperitoneal benign schwannoma near
      the inferior vena cava (IVC) using laparoscopic surgery. METHODS/RESULTS: A 33
      year-old woman presented with dull abdominal pain for several months. Magnetic
      resonance imaging confirmed the existence of a round, sharply demarcated
      retroperitoneal solid tumor, 42 x 52 mm in size, located between the anterior of
      the right kidney and the IVC, which was compressed but still patent. The lesion
      was laparoscopically resected, and pathologic examination revealed a degenerative
      schwannoma. CONCLUSION: Laparoscopic surgery is very useful and feasible in the
      diagnosis and treatment of retroperitoneal schwannoma, with minimal invasiveness
      and early postoperative recovery.

PMID- 20144536
TI  - Adverse effects of long-term proton pump inhibitor use: a review for the
      otolaryngologist.
AB  - OBJECTIVE: Proton pump inhibitors (PPIs) are the mainstay of current medical
      management for laryngopharyngeal reflux, and treatment often involves long-term
      use of this class of medications. The long-term adverse effects of PPI use have
      not been studied extensively, but several analyses have demonstrated
      epidemiological links between PPI use and adverse outcomes. These include altered
      mineral and vitamin absorption, orthopedic injury, acute coronary syndromes
      (ACS), and infectious risks. STUDY DESIGN: A PubMed search was performed for
      subject headings, including PPIs and adverse outcomes. Relevant studies were
      included in this review. Studies were compiled, reviewed, and compared in a
      narrative form. RESULTS: Several epidemiological links between PPI use and
      metabolic, infectious, cardiac, and orthopedic adverse outcomes were found. No
      definite causal effects were identified. CONCLUSION: Given these epidemiological
      patterns, we recommend that the clinician be aware of these possible unintended
      consequences. In addition, we recommend consideration of dual-energy X-ray
      absorptiometry (DEXA) bone density scans in at-risk patients who have not been
      previously tested. We recommend consideration of vitamin B12 and iron levels in
      selected patients who are at high risk. We also recommend close communication
      with our cardiology colleagues, as we attempt to ascertain the relationship
      between clopidogrel and PPI use. We recommend caution in the use of omeprazole in
      patients undergoing active treatment for ACS. Finally, we recommend consideration
      of Helicobacter pylori or serum gastrin level testing in patients with known risk
      factors for gastric carcinoma.

PMID- 20144537
TI  - Melanocortin-3 receptor gene variants: association with childhood obesity and
      eating behavior in Chilean families.
AB  - OBJECTIVE: To evaluate the association between melanocortin-3 receptor common
      genetic polymorphisms with childhood obesity and eating behavior in Chilean
      families. METHODS: Two hundred twenty-nine obese children (6-12 y old, body mass
      index >95th percentile of Centers for Disease Control and Prevention/National
      Center for Health Statistics, 2000) and 270 parents were selected. Genotypes for
      MC3R genetic markers -239A>G, 17C>A (Thr6Lys), 241G>A (Val81Ile), +2138InsCAGACC,
      and microsatellite D20s32e were determined. Eating behavior scores were computed
      using the Child Eating Behavior Questionnaire and a shorter version of the Three
      Factor Eating Questionnaire adapted for evaluating eating inclinations in
      children. Genotype-obesity associations were assessed by the Transmission
      Disequilibrium Test. Non-parametric tests were used to compare eating behavior
      scores across study groups. RESULTS: Allelic frequencies of -239G, 17A, 241A, and
      +2138InsCAGACC were estimated as 4.5%, 5.9%, 5.6%, and 17.6%, respectively, in
      obese children. The Transmission Disequilibrium Test in case-parent trios
      revealed no significant associations between childhood obesity and genetic
      markers, including the microsatellite D20s32e. In girls, we found significantly
      higher scores of the emotional eating subscale in carriers of the +2138InsCAGACC
      compared with non-carriers (P=0.04). In boys, carriers of 17A and 241A showed
      lower scores for the emotional eating subscale (P=0.01), whereas carriers of
      +2138InsCAGACC showed significantly lower scores for the enjoyment of food
      subscale compared with non-carriers (P=0.04). CONCLUSIONS: There is not
      sufficient evidence to support the contribution for common melanocortin-3
      receptor variants in childhood obesity. However, our results are concordant for a
      role of melanocortin-3 receptor variants in some dimensions of eating behavior
      such as emotional eating and enjoyment of food.

PMID- 20144538
TI  - Extreme oral manifestations in a Marfan-type syndrome.
AB  - A 12-year-old girl with an otherwise typical Marfan syndrome (Ghent criteria
      fulfilled) presented with highly unusual oral manifestations consisting of
      supernumerary teeth and severe dental crowding. Pathological examination of the
      supernumerary teeth revealed an elevated number of pulpoliths. No mutation in the
      FBN1, TGFBR1 and TGFBR2 genes was identified despite exhaustive screening,
      suggesting that another gene defect could explain this association of marfanoid
      features with dental abnormalities.

PMID- 20144539
TI  - Improving the data to strengthen the global response to HIV among people who
      inject drugs.
AB  - Recent systematic reviews have provided a global picture of injecting drug use,
      HIV and the global response to HIV epidemics among people who inject drugs. They
      have also revealed significant gaps in our knowledge, in both the problem and the
      response. It is clear that the prevalence of injecting drug use, and of HIV among
      injecting populations, varies geographically, differing hugely both within and
      across countries. In many cases, however, data on the number of drug injectors,
      and of the proportion who are living with HIV, is often unavailable or
      inaccurate, and gaps exist in many low income countries. The response to
      injecting drug use and HIV also varies hugely; both the nature and the scale of
      the response show marked geographic variation. The lack of quality data acts as
      an impediment to accurate assessments of effective and targeted responses to HIV
      among people who inject drugs. It is encouraging that the comprehensive suite of
      interventions considered "essential" by UN agencies in the response to HIV among
      people that inject drugs is being introduced in more countries now than ever
      before. Nonetheless, there remains an urgent need for more and higher quality
      data to be collected, in order to sufficiently inform, improve and ultimately
      evaluate the response.

PMID- 20144540
TI  - In rehabilitation's name? Ending institutionalised cruelty and degrading
      treatment of people who use drugs.

PMID- 20144541
TI  - A plant-tissue-based biophotonic method for herbicide sensing.
AB  - Herbicide application incurs water contamination and thus effective herbicide
      detection methods are needed. In this research, a kinetic model was developed to
      describe the processes of herbicide diffusion into plant tissues and binding to
      the active sites. DCMU [3-(3,4-dichlorophenyl)-1,1-dimethylurea], a commonly used
      herbicide, was used as a test chemical and its diffusion into plant leaves and
      binding to plastoquinone B (Q(B)) sites were analyzed by using the model. The
      dependency of delayed fluorescence (DF) emission on unbound Q(B) sites was first
      derived theoretically and then observed experimentally. This yields a biophotonic
      method to measure the concentrations of DCMU and other herbicides that function
      by a similar mechanism. Experiments were performed to validate the developed
      method.

PMID- 20144542
TI  - Nature and nurture in protein folding and binding.

PMID- 20144543
TI  - Purification, characterization, and cloning of a novel phytase with low pH
      optimum and strong proteolysis resistance from Aspergillus ficuum NTG-23.
AB  - A novel phytase was isolated from Aspergillus ficuum NTG-23 with a procedure
      involving ion-exchange chromatography on DEAE-cellulose, CM-cellulose and FPLC
      gel filtration on Superdex 75. The protein exhibited a molecular mass of 65.5kDa
      in gel filtration and SDS-PAGE. It possessed an optimal pH of 1.3 and an optimal
      temperature of 67 degrees C, and manifested a K(m) of 0.295mM and a V(max) of
      55.9nmol (phosphate)/min. Phytase activity was not significantly affected by
      metal ions such as Ca(2+), Mg(2+), Mn(2+), Zn(2+), but was slightly stimulated in
      the presence of EDTA. The phytase was stable at 60 degrees C with no obvious loss
      of activity upon its incubation at 70 degrees C for 20min. The enzyme exhibited a
      broad substrate selectivity and showed strong resistance toward pepsin and
      trypsin. The unique properties suggest that the phytase has the potential to be
      useful as an animal feed supplement.

PMID- 20144544
TI  - Tellimagrandin I, HCV invasion inhibitor from Rosae Rugosae Flos.
AB  - By use of the model virus, expressing the HCV envelope proteins E1 and E2,
      bioassay guided separation of the MeOH extract from Rosa rugosa Thunb. disclosed
      tellimagrandin I (1) together with eugeniin (2) and casuarictin (3) as the potent
      HCV invasion inhibitors. Furthermore, structure-activity relationship analysis of
      some relative tannins including the synthesized analogs elucidated the partial
      structures crucial for potent activity of 1.

PMID- 20144545
TI  - LXXLL peptide mimetics as inhibitors of the interaction of vitamin D receptor
      with coactivators.
AB  - Suppression of vitamin D receptor (VDR)-mediated transcription is expected be of
      therapeutic value in Paget's disease. Once an agonist activates VDR, recruitment
      of additional coactivator proteins is essential for transcription. Neither non
      secosteroidal VDR antagonists nor non-peptide coactivator binding inhibitors for
      VDR have been reported so far. Based on the X-ray structure of VDR and an LXXLL
      containing peptide fragment of the coactivator (where L is leucine and X is any
      amino acid), which adopts a partially alpha-helical conformation, benzodiazepine
      molecules were rationally designed as non-peptide coactivator mimetics. TR-FRET
      assay showed that the synthesized compounds inhibited the interaction between VDR
      and a coactivator peptide fragment. Compound 2 showed an IC(50) of 20microM.
      Compound 2 also inhibited VDR-mediated transcription, and this activity was
      independent of the concentration of co-existing agonist. Furthermore, compound 2
      did not inhibit estrogen receptor alpha-mediated transcription, indicating that
      it is not a non-selective inhibitor of other nuclear receptors.

PMID- 20144546
TI  - Replacement of pyrazol-3-yl amine hinge binder with thiazol-2-yl amine: Discovery
      of potent and selective JAK2 inhibitors.
AB  - Thiazol-2-yl amine was identified as an isosteric replacement for pyrazol-3-yl
      amine during our efforts to identify potent and selective JAK2 inhibitors. The
      rationale, synthesis and biological evaluation of several analogs is reported,
      along with the in vivo evaluation of the lead compounds.

PMID- 20144547
TI  - Cytotoxic and anti-inflammatory cembranoids from the Dongsha Atoll soft coral
      Sarcophyton crassocaule.
AB  - Five new cembranoids, sarcocrassocolides A-E (1-5), along with three known
      cembranoids 6-8, have been isolated from a Formosan soft coral Sarcophyton
      crassocaule. The structures of the new metabolites were elucidated by extensive
      spectroscopic analysis and the absolute configuration of 1 was determined by a
      modified Mosher's method. Compounds 1-4 exhibited significantly cytotoxic
      activity against a limited panel of cancer cell lines. Compounds 1-4, 6 and 8
      were shown to exert significant in vitro anti-inflammatory activity in LPS
      stimulated RAW264.7 macrophage cells. Compound 6 also significantly inhibited the
      accumulation of pro-inflammatory COX-2 protein.

PMID- 20144548
TI  - On carbon dioxide storage based on biomineralization strategies.
AB  - This study focuses on the separation and storage of the global warming greenhouse
      gas CO(2), and the use of natural biocatalysts in the development of technologies
      to improve CO(2) storage rates and provide new methods for CO(2) capture.
      Carbonic anhydrase (CA) has recently been used as a biocatalyst to sequester
      CO(2) through the conversion of CO(2) to HCO(-) in the mineralization of CaCO(3).
      Biomimetic CaCO(3) mineralization for carbon capture and storage offers potential
      as a stable CO(2) capture technology. In this report, we review recent
      developments in this field and assess disadvantages and improvements in the use
      of CA in industrial applications. We discuss the contribution that understanding
      of mechanisms of CO(2) conversion to CO(3)(-) in the formation and regeneration
      of bivalve shells will make to developments in biomimetic CO(2) storage.

PMID- 20144549
TI  - Emerging role of small ribonucleic acids in gastrointestinal tumors.
AB  - Small regulatory ribonucleic acids (RNAs) are recently recognized as being
      connected with a growing list of common diseases such as: cancer, heart disease,
      diabetes and inflammation and to date more than 5,000 publications are recorded
      on PubMed alone. Specific pathways generate each class of RNAs and their
      activities converge in the process of silence interference. In gastrointestinal
      malignancies microRNAs are deregulated, sometimes found in higher or lower levels
      depending on the type of malignancy and stage of the disease, functioning either
      as tumor suppressors or as oncogenes they interact forming regulatory loops with
      known transcription factors and signaling pathways. MiRNAs extracted from
      archived tissue biopsies can be used effectively as diagnostic, prognostic tools
      and molecular markers because they are stable over time and resistant to RNAse
      degradation. The distinct physiology of small RNAs may translate in more targeted
      cancer therapies in the near future.

PMID- 20144550
TI  - Recruitment of blood donors in Burkina Faso: how to avoid donations from family
      members?
AB  - Burkina Faso is a continental West African country of approximately 16 M people
      whose transfusion needs were covered by 66,210 blood units collected mostly in 4
      regional transfusion centers part of a national network but also from hospital
      based smaller blood centers. The first group of blood centers relies almost
      exclusively on volunteer, non-remunerated, blood donors and only approximately
      32.7% of them are repeating donation. In contrast, hospital-based blood centers
      rely nearly exclusively on family/replacement donors. The general strategy of the
      national blood transfusion network was to base the system exclusively on
      volunteer donors, which was nearly accomplished overall and completely at Bobo
      Dioulasso, the largest center. However, despite considerable increase in blood
      collection, the overall blood supply remains low (4.7 units/1000 inhabitants) and
      worsens during the secondary school recesses since young student blood
      constitutes the most part of volunteer donors. To overcome such shortages, mobile
      blood collection sessions are organized in alternate sites such as military
      barracks or places of worship but with limited success. Another critical issue is
      that despite considerable efforts and help from community advocates, only 32.7%
      of volunteers repeat donation limiting the considerably safety advantage of a
      pool of regular donors.

PMID- 20144551
TI  - African-American adolescent girls' initiation of sexual activity: survival
      analysis.
AB  - PURPOSE: African-American adolescent females tend to initiate participation in
      sexual activity at an earlier age than Caucasian adolescent females. Early
      initial participation in sexual activity is associated with increased risk of HIV
      infection. However, limited prospective data are available on the rate at which
      African-American adolescent females delay their initial participation in sexual
      activity. The purpose is to determine low-income, inner-city, African-American
      adolescent females' survival or continued nonparticipation in sexual activity
      over a 20-month period and to determine predictors associated with survival.
      METHODS: A longitudinal, quasi-experimental research design with multiple data
      collection points was used. The convenience sample consisted of 396 African
      American females with a mean age of 12.4 years (SD = 1.1 years) and their
      mothers. The adolescents completed questionnaires assessing perceptions of
      maternal monitoring, HIV transmission knowledge, self-efficacy to refuse sex,
      intention to refuse sex, and age. Their mothers completed questionnaires
      assessing perception of maternal monitoring, safer sex self-efficacy, marital
      status, and educational level. At baseline, the adolescents reported
      nonparticipation in sexual activity. Survival analysis was conducted to determine
      the timing and predictors of sexual activity initiation for these adolescents.
      FINDINGS: Of the 396 adolescents, 28.5% did not survive; they participated in
      sexual activity within the 20-month period. Predictors of non-survival were the
      adolescents' age, perception of maternal monitoring, and intention to refuse sex.
      CONCLUSION: Findings suggest interventions that increase maternal monitoring and
      adolescents' intentions to refuse sex could be beneficial in delaying sexual
      activity.

PMID- 20144552
TI  - The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and
      parameters of calcium and bone metabolism--a longitudinal study.
AB  - BACKGROUND: Chronic antiepileptic drug use is associated with bone loss. We
      sought to assess the longitudinal effect of antiepileptic drug on serum 25
      hydroxyvitamin D [25(OH)D] levels and bone mineral metabolism markers. METHODS:
      Patients in the emergency services or those in neurology outpatient department
      with history of seizure were characterized and included in the study
      prospectively. Daily dietary intake of calories, calcium, phosphorus and phytates
      were characterized by dietary recall method. Base line bone mineral parameters -
      serum calcium, phosphorus, alkaline phosphatase (SAP), tartrate resistant acid
      phosphatase (TRACP), 25(OH)D levels, parathyroid hormone (PTH) and urinary
      calcium creatinine ratio (Ca.Cr), urinary calcium/kg/bodyweight (BW) and
      phosphate excretion index (PEI) were determined. Patients on AED therapy with
      normal 25(OH)D levels were followed up and were re-evaluated at the end of 6
      months. RESULTS: The daily dietary calcium intake of the subjects was lower than
      the RDA (Recommended Dietary Allowance) by ICMR (Indian Council of Medical
      Research). The diet was high in phytates. Two-thirds of the recruited subjects
      were vitamin D deficient. Subjects with normal 25(OH)D levels at base line showed
      a significant fall of 25(OH)D levels, urinary calcium, urinary calcium/kg/BW and
      TRACP levels at the end of 6 months irrespective of the AED used or the plasma
      level of AED. CONCLUSIONS: Hypovitaminosis D is common in our population.
      Subjects with normal 25(OH)D levels, irrespective of the type of antiepileptic
      medications even at sub-therapeutic serum levels of the drug, went into 25(OH)D
      deficiency and insufficiency states. Theoretically it can be worthwhile to
      supplement calcium and vitamin D even before initiation of antiepileptic therapy.

PMID- 20144553
TI  - Malformations of cortical development (MCDs) and epilepsy: experience from a
      tertiary care center in south India.
AB  - INTRODUCTION: Malformations of cortical development (MCDs) are increasingly
      recognized as important cause of epilepsy, especially refractory epilepsy. In
      developing countries like India, where the facilities for sophisticated imaging
      are not easily accessible to all, the prevalence and the types of cortical
      malformations are largely unknown. Hence this preliminary study has been
      undertaken to examine the relation between epilepsy and malformations of cortical
      development in a resource-limited setting. AIMS: To study various types of
      malformations of cortical development (MCDs) associated with epilepsy and to
      correlate with their clinical semiology. SETTINGS AND DESIGN: The study was
      conducted in a tertiary care neurological center in south India. Cohort included
      all patients with epilepsy associated with cortical malformation on neuroimaging.
      METHODS AND MATERIALS: Neuroimaging data of all patients with epilepsy were
      evaluated for a 5-year period from 1998 to 2003, for the presence of cortical
      malformations. The case records of those patients with cortical malformations
      were taken from the medical records department and the clinical and
      electrophysiological data were analyzed. RESULTS: We are reporting 34 cases of
      MCDs evaluated during the 5-year period. The mean age of the cohort was 15.1 (+/
      12.2) years, with a range from 3 months to 45 years and 52.9% were males. Mean
      age at seizure onset was 7.2 years (+/-7.8), with a mean duration of seizure of
      8.1 years (+/-7.7). Delayed motor and mental milestones were present in 15
      patients (44.1%) and positive family history of seizure/epilepsy was seen in 9
      patients (26.5%). Cortical malformations were most often associated with partial
      seizures (19/34, 55.9%). The most common type of seizure was complex partial
      seizure, seen in 12 patients (35.3%). Majority had very frequent, uncontrolled
      seizures with 16 (47.1%) patients having a seizure frequency of more than one per
      day. Heterotopias were seen in 14 patients (41.2%), in isolation in 5 (14.7%)
      patients and in combination with other malformations in 9 (26.5%) patients.
      Pachygyria was present as an isolated anomaly in five (14.7%) patients and
      combined with other abnormalities in eight (23.5%) patients. Cortical dysplasia
      was seen in 5 (14.7%) patients, hemimegalencephaly in two patients,
      polymicrogyria in two patients, lissencephaly and schizencephaly were seen in one
      patient each. EEG demonstrated focal epileptiform discharges in 59.1%, while
      generalized epileptiform discharges were seen in 22.7% of patients. Twenty-seven
      out of 34 (79.4%) patients had refractory/difficult to treat epilepsy.
      CONCLUSIONS: Malformations of cortical development are a heterogeneous group of
      disorders, associated with developmental delay and refractory seizures but
      seizures usually do not have pathognomonic semiologic features. Possibility of
      MCDs should be considered during the evaluation of refractory epilepsy cases.

PMID- 20144554
TI  - Improving the quality of reporting in veterinary journals: how far do we need to
      go with reporting guidelines?

PMID- 20144555
TI  - Inactivation of insulin-like-growth factors diminished the anabolic effects of
      pregnancy-associated plasma protein-A (PAPP-A) on bone in mice.
AB  - In vivo studies have provided ubiquitous evidence that pregnancy-associated
      plasma protein-A (PAPP-A) functions as a potent anabolic factor. While some
      evidence supports the prediction that increasing IGF bioavailability contributes
      to the anabolic effects of PAPP-A, definitive evidence has been lacking. This
      important issue has been addressed in this study using a unique mouse model in
      which PAPP-A was overexpressed in bone either alone or together with a protease
      resistant IGFBP-4 analog (PRBP-4) which serves as an IGF inhibitor. PAPP-A
      transgenic mice exhibited a 25% increase in skull bone mineral density (BMD)
      whereas PRBP-4 transgenic mice showed a 20-25% decrease in this parameter at an
      age of 3months. Femur/tibia size-related parameters were significantly increased
      in PAPP-A transgenic mice but decreased in PRBP-4 transgenic mice. This data
      clearly demonstrates that PAPP-A transgenic mice exhibit opposite phenotypes in
      both flat bone and long bone compared to PRBP-4 transgenic mice which have
      reduced IGF bioavailability in bone. Importantly, PRBP-4 and PRBP-4/PAPP-A double
      transgenic mice shared essentially identical phenotypes in both flat and long
      bones. Calvarial thickness, skull BMD and long bone parameters were reduced to
      similar degrees in PRBP-4 and PRBP-4/PAPP-A transgenic mice relative to wild-type
      littermates. Our findings provide compelling evidence that PAPP-A increases bone
      formation primarily by increasing IGF bioavailability and that other alternative
      pathways may play a negligible role in mediating the anabolic effect of PAPPA in
      bone. This clear definition of PAPP-A's mechanism of action is critical for
      future translational studies on the therapeutic application of PAPP-A.

PMID- 20144556
TI  - Morphological analysis of astrocytes in the hippocampus in mechanical
      asphyxiation.
AB  - The present study investigated the morphology of astrocytes in the hippocampus
      and serum S100B levels in cases of mechanical asphyxia due to neck compression
      (n=23: atypical hanging, n=7; ligature/manual strangulation, n=16) with regard to
      the classical autopsy findings, compared with those of other types of
      asphyxiation (n=9) and acute myocardial infarction/ischemia (AMI, n=20). The
      decrease in intact astrocyte number, as shown by S100 and GFAP-immunostaining,
      was larger for asphyxiation due to neck compression compared with that for other
      asphyxiation and AMI, showing a correlation with the increase in the serum S100B
      levels. The decrease in intact astrocyte number and increase in serum S100B were
      closely related to the severity of conjunctival petechial hemorrhage and
      fracture(s) of the hyoid bone and/or thyroid cartilage in asphyxia due to neck
      compression. These findings suggest that hippocampal astrocyte injury is caused
      by cerebral hypoxia accompanied by congestion, especially in mechanical asphyxia
      due to neck compression.

PMID- 20144557
TI  - Multiple stress factors and the emission of plant VOCs.
AB  - Individual biotic and abiotic stresses, such as high temperature, high light and
      herbivore attack, are well known to increase the emission of volatile organic
      compounds from plants. Much less is known about the effect of multiple, co
      occurring stress factors, despite the fact that multiple stresses are probably
      the rule under natural conditions. Here, after briefly summarizing the basic
      effects of single stress factors on the volatile emission of plants, we survey
      the influence of multiple stresses. When two or more stresses co-occur their
      effects are sometimes additive, while in other cases the influence of one stress
      has priority. Further investigations on the effects of multiple stress factors
      will improve our understanding of the patterns and functions of plant volatile
      emission.

PMID- 20144558
TI  - High field cardiac magnetic resonance imaging--current and future perspectives.
AB  - Potential advantages of high field cardiac magnetic resonance imaging include
      superior signal-to-noise ratio, image contrast and spectral separation. These
      might be used to improve spatial and/or temporal resolution and imaging speed.
      However, high field imaging presents new challenges to the operator, including
      increased magnetic field heterogeneity, susceptibility, artefacts and higher
      specific absorption rate. Recently, studies have reported on the clinical utility
      of cardiac magnetic resonance imaging at 3 Tesla in the assessment of myocardial
      function, perfusion and viability, and coronary arteries. The results of these
      clinical studies are reviewed, as well as emerging applications in myocardial
      tagging and cardiac spectroscopy.

PMID- 20144559
TI  - Serum thromboxane B2 compared to five other platelet function tests for the
      evaluation of aspirin effect in stable cardiovascular disease.
AB  - BACKGROUND: To assess the role of serum thromboxane B(2) (TXB(2)) measurements
      and the correlation between platelet function studies, in patients with stable
      cardiovascular disease on aspirin or clopidogrel. METHODS: 76 patients (47 on
      aspirin, 16 clopidogrel, 13 both) underwent assessment of TXB(2), whole blood
      aggregometry (WBA) after stimulation with (i) arachidonic acid (0.5mM), (ii) ADP
      (5 microM), (iii) collagen (1 and 5 microg/ml), PFA-100, and Cone and Plate
      Analyzer. Clopidogrel patients were additionally assessed by the VerifyNow
      System. RESULTS: TXB(2) values ranged between 0.2 and 56.2 ng/ml, with
      significant separation between those taking aspirin, clopidogrel and controls
      (0.45 ng/ml vs 6.85 ng/ml vs 12.97 ng/ml, p<0.001). There was moderate
      correlation between WBA-AA and TXB(2) (r=0.487, p<0.001), PFA-100((R)) (r=0.599,
      p<0.001), WBA-Col1 (r=0.424, p<0.001), WBA-Col1:5 (r=0.417, p<0.001), and between
      TXB(2) and PFA-100((R)) (r=0.509, p<0.001). The prevalence of aspirin non
      responders for WBA-AA, TXB(2), PFA-100((R)), CPA and Coll1:5 was 13.1%, 8.2%,
      14.8%, 9.7% and 16.4% respectively. Individual patients were not consistently
      classified as aspirin non-responders in all tests. Those with inadequate aspirin
      response on > or =3 tests had higher TXB(2) levels (mean 1.57+/-1.66, range 0.553
      4.45 vs mean 0.45+/-0.18, range 0.23-1.50) (p=0.001). Clopidogrel suppressed
      TXB(2) (p=0.02), WBA-AA (p<0.001), WBA-Col1 (p=0.012) and WBA-ADP (p<0.001)
      compared to controls. TXB(2) in patients ingesting fish oil tablets was lower
      compared to those without (0.4 ng/ml vs 0.52 ng/ml, p=0.004). Obesity was
      associated with higher TXB(2) values (0.61 vs 0.41, p=0.01). CONCLUSION: Serum
      TXB(2) measurements are a direct measure of the pharmacological effect of
      aspirin, are easily performed and correlate with other measures of platelet
      function. Serum TXB(2) measurements could be a useful sole measure of aspirin non
      response, and may be even more predictive when performed in tandem with a global
      measure of platelet function. Aspirin and clopidogrel both suppressed several
      platelet pathways.

PMID- 20144560
TI  - Non-invasive cardiac imaging: 2010 and beyond.

PMID- 20144561
TI  - Mid-term results of the Hancock II valve and Carpentier-Edward Perimount valve in
      the pulmonary portion in congenital heart disease.
AB  - BACKGROUND: As the number of cases with artificial pulmonary valve implantation
      increases for congenital heart disease, the number of young adults with
      artificial pulmonary valves has also increased. METHODS: From 2000 to 2007, 146
      artificial valves, such as the Carpentier-Edward Perimount, Hancock II, Biocor,
      homograft and hand-made valves were implanted for pulmonary valve in 132 patients
      with various forms of congenital heart disease. Among them, the outcomes of the
      Carpentier-Edward Perimount (n=63) and the Hancock II (n=40) valves were reviewed
      retrospectively. The mean age at initial implantation was 12.8+/-6.6 years. The
      overall duration of follow up was 36.0+/-24.2 months. RESULTS: There was an early
      death due to right ventricular failure with intractable ventricular arrhythmia
      and 3 late deaths due to progressive right ventricular failure, dilated
      cardiomyopathy and infective endocarditis. The overall survival and re-operation
      free rate was 96.3% and 89.8% respectively. Eight out of 63 Carpentier-Edward
      patients (12.6%) underwent re-replacement at 49.2+/-25.2 months. The re-operation
      free rates were 97.7%, 87.7% and 50% at 1, 3 and 5 years respectively. There was
      no re-operation required for the 40 Hancock II patients over 18.0+/-10.8 months.
      There was no statistical significance in the re-operation free rates between
      these 2 valves (p-value=0.51). CONCLUSIONS: The overall survival rate associated
      with pulmonary valve bioprosthetic valve implantation was acceptable. However,
      the re-operation freedom rate was not satisfactory at mid-term for the Carpentier
      Edward.

PMID- 20144562
TI  - The Gunther-Tulip retrievable filter: a method for assessing tilting of the
      filter.
AB  - PURPOSE: Tilting of the Gunther-Tulip filter may be responsible for failure or
      difficulty to retrieve. Assessment of the filter tilt can be difficult when only
      AP imaging is available. This study is performed in vitro to develop a simple
      method to assess the Gunther-Tulip filter for tilting. MATERIALS AND METHODS: A
      model consisting of a plastic tube was used to simulate vena cava. A Gunther
      Tulip filter was placed centred or tilted within the tube at various positions
      and radiograms were taken in AP, lateral, and craniocaudally angled projections.
      The images were analysed to determine the actual degree of tilt, the distance
      between the limb hooks on AP radiograms and the craniocaudal angulation degree
      needed to align the limb hooks linearly. RESULTS: When the filter was centred or
      tilted laterally, all limb hooks of the filter were aligned linearly on AP
      radiograms. When the filter was tilted in AP or oblique direction, linear
      alignment of the limb hooks was lost and the ventral and dorsal limb hooks showed
      separation on AP projection. The amount of separation and the craniocaudal angles
      to align the filter hooks corresponded to actual tilt angles. CONCLUSION: Loss of
      linear alignment of limb hooks in AP radiograms may suggest the presence of tilt
      in the AP plane. Significant separation of limb hooks should be alarming for
      significant filter tilt, and further evaluation of the filter position by CT scan
      or lateral cavogram should be obtained prior to planning of the retrieval.

PMID- 20144563
TI  - Preimplantation genetic haplotyping: 127 diagnostic cycles demonstrating a
      robust, efficient alternative to direct mutation testing on single cells.
AB  - Preimplantation genetic diagnosis using whole genome amplification and a
      haplotyping approach (PGH) was first described in 2006 and suggested as an
      efficient alternative to single-cell PCR for monogenic disorders. DNA from single
      cells was amplified using multiple displacement amplification; the resulting
      products were then tested using disease-specific PCR multiplexes applied under
      standard laboratory conditions to determine the haplotypes in the embryo. This
      study reports on a total of 127 completed biopsy cycles for 101 couples at risk
      of: autosomal recessive disease (71 cycles, 53 couples including one germ-line
      mosaic carrier), autosomal dominant disease (31 cycles, 26 couples including one
      germ-line mosaic carrier), X-linked recessive disease (18 cycles, 16 couples
      including one germ-line mosaic carrier), X-linked dominant disease (six cycles,
      five couples) and a double inheritance of both autosomal and X-linked recessive
      diseases (one cycle, one couple). Of these, 107 cycles reached embryo transfer.
      Overall success rates were: fetal heart beat-positive pregnancies (FHB+)/biopsy
      cycle=28%; FHB+/embryo transfer=34%; FHB+/couple=36%; 26 babies born, 13 ongoing
      pregnancies. These data demonstrate that PGH provides a robust, efficient and
      successful alternative to single-cell PCR for monogenic diseases.

PMID- 20144564
TI  - The SbcCD complex of Deinococcus radiodurans contributes to radioresistance and
      DNA strand break repair in vivo and exhibits Mre11-Rad50 type activity in vitro.
AB  - Deinococcus radiodurans lacks a homologue of the recB and recC genes, and the
      sbcA/B genes, of Escherichia coli. Thus, DNA strand break repair in Deinococcus
      proceeds by pathways that do not utilize these proteins. Unlike E. coli, the
      absence of recBC and sbcA/sbcB, and presence of only sbcC and sbcD in
      Deinococcus, indicates an enigmatic role of SbcCD in this bacterium. Studies on
      sbcCD mutation in Deinococcus showed nearly a 100-fold increase in gamma
      radiation sensitivity as compared to wild type. The mutant showed a higher rate
      of in vivo DNA degradation during the post-irradiation recovery period that
      corresponds to the RecA-dependent DSB repair phase. These cells showed a typical
      NotI pattern of DNA reassembly during the early phase of DSB repair, but were
      defective for the subsequent RecA-dependent phase II of DSB repair. Hydrogen
      peroxide had no effect on cell survival of the mutant. While its tolerance to
      higher doses of UVC and mitomycin C was significantly decreased as compared to
      wild type. Purified recombinant SbcCD proteins showed single-stranded
      endonuclease and 3'-->5' double-stranded DNA exonuclease activities similar to
      that of the Mre11-Rad50 complex, which is required for DNA strand break repair in
      higher organisms. These results suggested that the Mre11-Rad50 type nuclease
      activity of SbcCD proteins contributes to the radiation resistance of D.
      radiodurans perhaps by promoting the RecA-dependent DSB repair required for
      polyploid genome maturation.

PMID- 20144565
TI  - A convenient method for saponin isolation in tumour therapy.
AB  - Saponinum album (Merck), which is a crude mixture of saponins from Gypsophila
      paniculata L., was shown to improve the anti cancer therapy when used in vivo in
      combination with saporin-based targeted toxins. Unfortunately saponinum album
      cannot be used for further development since Merck has ceased its production in
      the 1990s. As pure saponins are mandatory for use in medical purposes we
      developed a convenient method for saponin isolation directly from the roots of
      Gypsophila paniculata L. The developed method is rapid, cheap and scaling up is
      also possible. By combining dialysis and HPLC three saponins were isolated in a
      one-step procedure. Chemical structures of the purified saponins were
      characterized by extensive one and two-dimensional NMR-spectroscopy and by using
      ESI-TOF-MS. The biological activities of the purified saponins were also
      investigated. The method presented herein enabled a rapid and cheap isolation of
      saponins for tumour therapy.

PMID- 20144581
TI  - Malaria research--diversity and control: a Sweden-Japan joint seminar.

PMID- 20144582
TI  - The regulation of OXPHOS by extramitochondrial calcium.
AB  - Despite extensive research, the regulation of mitochondrial function is still not
      understood completely. Ample evidence shows that cytosolic Ca2+ has a strategic
      task in co-ordinating the cellular work load and the regeneration of ATP by
      mitochondria. Currently, the paradigmatic view is that Cacyt2+ taken up by the
      Ca2+ uniporter activates the matrix enzymes pyruvate dehydrogenase, alpha
      ketoglutarate dehydrogenase and isocitrate dehydrogenase. However, we have
      recently found that Ca2+ regulates the glutamate-dependent state 3 respiration by
      the supply of glutamate to mitochondria via aralar, a mitochondrial
      glutamate/aspartate carrier. Since this activation is not affected by ruthenium
      red, glutamate transport into mitochondria is controlled exclusively by
      extramitochondrial Ca2+. Therefore, this discovery shows that besides
      intramitochondrial also extramitochondrial Ca2+ regulates oxidative
      phosphorylation. This new mechanism acts as a mitochondrial "gas pedal",
      supplying the OXPHOS with substrate on demand. These results are in line with
      recent findings of Satrustegui and Palmieri showing that aralar as part of the
      malate-aspartate shuttle is involved in the Ca2+-dependent transport of reducing
      hydrogen equivalents (from NADH) into mitochondria. This review summarises
      results and evidence as well as hypothetical interpretations of data supporting
      the view that at the surface of mitochondria different regulatory Ca2+-binding
      sites exist and can contribute to cellular energy homeostasis. Moreover, on the
      basis of our own data, we propose that these surface Ca2+-binding sites may act
      as targets for neurotoxic proteins such as mutated huntingtin and others. The
      binding of these proteins to Ca2+-binding sites can impair the regulation by
      Ca2+, causing energetic depression and neurodegeneration.

PMID- 20144583
TI  - Kinetic model of the inhibition of respiration by endogenous nitric oxide in
      intact cells.
AB  - Nitric oxide (NO) inhibits mitochondrial respiration by decreasing the apparent
      affinity of cytochrome c oxidase (CcO) for oxygen. Using iNOS-transfected HEK 293
      cells to achieve regulated intracellular NO production, we determined NO and O(2)
      concentrations and mitochondrial O(2) consumption by high-resolution respirometry
      over a range of O(2) concentrations down to nanomolar. Inhibition of respiration
      by NO was reversible, and complete NO removal recovered cell respiration above
      its routine reference values. Respiration was observed even at high NO
      concentrations, and the dependence of IC(50) on [O(2)] exhibits a characteristic
      but puzzling parabolic shape; both these features imply that CcO is protected
      from complete inactivation by NO and are likely to be physiologically relevant.
      We present a kinetic model of CcO inhibition by NO that efficiently predicts
      experimentally determined respiration at physiological O(2) and NO concentrations
      and under hypoxia, and accurately predicts the respiratory responses under
      hyperoxia. The model invokes competitive and uncompetitive inhibition by binding
      of NO to the reduced and oxidized forms of CcO, respectively, and suggests that
      dissociation of NO from reduced CcO may involve its O(2)-dependent oxidation. It
      also explains the non-linear dependence of IC(50) on O(2) concentration, and the
      hyperbolic increase of c(50) as a function of NO concentration.

PMID- 20144584
TI  - 4Pi microscopy reveals an impaired three-dimensional mitochondrial network of
      pancreatic islet beta-cells, an experimental model of type-2 diabetes.
AB  - Insulin production in pancreatic beta-cells is critically linked to mitochondrial
      oxidative phosphorylation. Increased ATP production triggered by blood glucose
      represents the beta-cells' glucose sensor. Type-2 diabetes mellitus results from
      insulin resistance in peripheral tissues and impaired insulin secretion.
      Pathology of diabetic beta-cells might be reflected by the altered morphology of
      mitochondrial network. Its characterization is however hampered by the complexity
      and density of the three-dimensional (3D) mitochondrial tubular networks in these
      cell types. Conventional confocal microscopy does not provide sufficient axial
      resolution to reveal the required details; electron tomography reconstruction of
      these dense networks is still difficult and time consuming. However,
      mitochondrial network morphology in fixed cells can also be studied by 4Pi
      microscopy, a laser scanning microscopy technique which provides an approximately
      7-fold improved axial resolution (approximately 100 nm) over conventional
      confocal microscopy. Here we present a quantitative study of these networks in
      insulinoma INS-1E cells and primary beta-cells in Langerhans islets. The former
      were a stably-transfected cell line while the latter were transfected with
      lentivirus, both expressing mitochondrial matrix targeted redox-sensitive GFP.
      The mitochondrial networks and their partial disintegration and fragmentation are
      revealed by carefully created iso-surface plots and their quantitative analysis.
      We demonstrate that beta-cells within the Langerhans islets from diabetic Goto
      Kakizaki rats exhibited a more disintegrated mitochondrial network compared to
      those from control Wistar rats and model insulinoma INS-1E cells. Standardization
      of these patterns may lead to development of morphological diagnostics for
      Langerhans islets, for the assessment of beta-cell condition, before their
      transplantations.

PMID- 20144585
TI  - Overexpression of gamma-tocopherol methyl transferase gene in transgenic Brassica
      juncea plants alleviates abiotic stress: physiological and chlorophyll a
      fluorescence measurements.
AB  - Tocopherols (vitamin E) are lipid soluble antioxidants synthesized by plants and
      some cyanobacteria. We have earlier reported that overexpression of the gamma
      tocopherol methyl transferase (gamma-TMT) gene from Arabidopsis thaliana in
      transgenic Brassica juncea plants resulted in an over six-fold increase in the
      level of alpha-tocopherol, the most active form of all the tocopherols.
      Tocopherol levels have been shown to increase in response to a variety of abiotic
      stresses. In the present study on Brassica juncea, we found that salt, heavy
      metal and osmotic stress induced an increase in the total tocopherol levels.
      Measurements of seed germination, shoot growth and leaf disc senescence showed
      that transgenic Brassica juncea plants overexpressing the gamma-TMT gene had
      enhanced tolerance to the induced stresses. Analysis of the chlorophyll a
      fluorescence rise kinetics, from the initial "O" level to the "P" (the peak)
      level, showed that there were differential effects of the applied stresses on
      different sites of the photosynthetic machinery; further, these effects were
      alleviated in the transgenic (line 16.1) Brassica juncea plants. We show that
      alpha-tocopherol plays an important role in the alleviation of stress induced by
      salt, heavy metal and osmoticum in Brassica juncea.

PMID- 20144586
TI  - Communication between mitochondria and nucleus: putative role for VDAC in
      reduction/oxidation mechanism.
AB  - Voltage dependent anion channel (VDAC) was identified in 1976 and since that time
      has been extensively studied. It is well known that VDAC transports metabolites
      across the outer mitochondrial membrane. The simple transport function is
      indispensable for proper mitochondria functions and, consequently for cell
      activity, and makes VDAC crucial for a range of cellular processes including ATP
      rationing, Ca2+ homeostasis and apoptosis execution. Here, we review recent data
      obtained for Saccharomyces cerevisiae cells used as a model system concerning the
      putative role of VDAC in communication between mitochondria and the nucleus. The
      S. cerevisiae VDAC isoform known as VDAC1 (termed here YVDAC) mediates the
      cytosol reduction/oxidation (redox) state that contributes to regulation of
      expression and activity of cellular proteins including proteins that participate
      in protein import into mitochondria and antioxidant enzymes. Simultaneously,
      copper-and-zinc-containing superoxide dismutase (CuZnSOD) plays an important role
      in controlling YVDAC activity and expression levels. Thus, it is proposed that
      VDAC constitutes an important component of a regulatory mechanism based on the
      cytosol redox state.

PMID- 20144587
TI  - Delivering cargoes into cancer cells using DNA aptamers targeting internalized
      surface portals.
AB  - Many evolving treatments for cancer patients are based on the targeted delivery
      of therapeutic cargoes to and into cancer cells. The advent of monoclonal
      antibodies and the use of peptide hormones, growth factors and cytokines have
      historically provided a spectrum of ligands needed to selectively target tumor
      associated antigens on cancer cells. However, issues linked to the size, cost and
      immunogenicity of protein-based ligands have led to the search for alternate
      ligand families. The advent of short synthetic oligonucleotide ligands known as
      aptamers now provides a simple strategy to select for membrane-impermeant
      aptamers tailored to precisely target internalized surface markers present on
      cancer cells. Here we described how 25-base long, synthetic single-stranded DNA
      aptamers were derived to bind to known internalized tumor markers such as CD33,
      CEA, MUC1 and Tn antigens and are imported through these surface portals into
      cancer cells. The key consequence of using internalized aptamers is their ability
      to accumulate inside the cells, thus routing their therapeutic cargoes to
      intracellular sites relevant to their action. Internalized aptamers are discussed
      in the context of how such ligands have been used to create a range of guided
      therapeutic agents ranging from drug-based conjugates up to targeted
      nanoparticles.

PMID- 20144588
TI  - Decreased calcium channel currents and facilitated epinephrine release in the
      Ca2+ channel beta3 subunit-null mice.
AB  - The beta subunits of voltage-dependent calcium channels are known to modify
      calcium channel currents through pore-forming alpha1 subunits. The beta3 subunit
      is expressed in the adrenal gland and participates in forming various calcium
      channel types. We performed a series of experiments in beta3-null mice to
      determine the role of the beta3 subunit in catecholamine release from the adrenal
      chromaffin system. Protein levels of N-type channel forming CaV2.2 and L-type
      forming CaV1.2 decreased. The beta3-null mice showed a decreased baroreflex,
      suggesting decreased sympathetic tonus, whereas plasma catecholamine levels did
      not change. Pulse-voltage stimulation revealed significantly increased
      amperometrical currents in beta3-null mice, while patch-clamp recordings showed a
      significant reduction in Ca(2+)-currents due to reduced L- and N-type currents,
      indicating facilitated exocytosis. A biochemical analysis revealed increased
      InsP3 production. In conclusion, our results indicate the importance of the beta3
      subunit in determining calcium channel characteristics and catecholamine release
      in adrenal chromaffin cells.

PMID- 20144589
TI  - Role of modulation of vascular endothelial growth factor and tumor necrosis
      factor-alpha in gastric ulcer healing in diabetic rats.
AB  - The aim of the present study was to assess the effect of drugs that increase
      gastric vascular endothelial growth factor (VEGF) and suppress gastric tumor
      necrosis factor-alpha (TNF-alpha) in gastric ulcer healing in streptozotocin
      induced diabetic rats. Sixty male albino rats were made diabetic by
      intraperitoneal (i.p.) streptozotocin injection and ten rats were injected i.p.
      by a single dose of saline. Six weeks following streptozotocin or saline
      injection, gastric ulcers were induced by serosal application of acetic acid.
      Three days after acetic acid application, rats were divided into: group I (non
      diabetic control), group II (streptozotocin-injected), groups III-VII
      (streptozotocin-injected rats treated with insulin, insulin and pentoxifylline,
      insulin and simvastatin, pentoxifylline as well as simvastatin, respectively, for
      7 days following acetic acid application. The use of insulin, combinations of
      insulin and pentoxifylline or simvastatin resulted in a significant decrease in
      gastric ulcer area, significant increase in epithelial regeneration assessed
      histologically, significant increase in gastric VEGF concentration, and gastric
      von Willebrand factor (vWF) as well as significant decrease in gastric TNF-alpha.
      A significant difference in gastric ulcer area as well as in gastric TNF-alpha,
      VEGF and vWF levels could be observed between rats that received combinations of
      insulin and pentoxifylline or simvastatin compared to rats that received either
      drug alone. Our results suggest the feasibility of a novel treatment strategy,
      namely pentoxifylline and simvastatin, for patients in whom impairment of ulcer
      healing constitutes a secondary complication of diabetes mellitus.

PMID- 20144590
TI  - Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob
      mice.
AB  - Nobiletin is a polymethoxylated flavone found in certain citrus fruits that
      exhibits various pharmacological effects including anti-inflammatory, antitumor
      and neuroprotective properties. The present study investigated the effects of
      nobiletin on insulin sensitivity in obese diabetic ob/ob mice, and the possible
      mechanisms involved. The ob/ob mice were treated with nobiletin (200mg/kg) for 5
      weeks. Nobiletin significantly improved the plasma glucose levels, homeostasis
      model assessment index, glucose tolerance in an oral glucose tolerance test and
      plasma adiponectin levels. In white adipose tissue (WAT), nobiletin significantly
      decreased the mRNA expression levels of inflammatory adipokines such as
      interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 and increased the
      mRNA expression levels of adiponectin, peroxisome proliferator-activated receptor
      (PPAR)-gamma and its target genes. At the same time, nobiletin increased the
      glucose transporter (Glut) 4 expression levels in the whole plasma membrane, and
      Glut1 and phospho-Akt expression in the whole cell lysates in WAT and muscle.
      Nobiletin also increased Glut4 protein expression level in the whole cell lysates
      of the muscle. Taken together, the present results suggest that nobiletin
      improved the hyperglycemia and insulin resistance in obese diabetic ob/ob mice by
      regulating expression of Glut1 and Glut4 in WAT and muscle, and expression of
      adipokines in WAT.

PMID- 20144591
TI  - The effect of stereochemistry on the thermodynamic characteristics of the binding
      of fenoterol stereoisomers to the beta(2)-adrenoceptor.
AB  - The binding thermodynamics of the stereoisomers of fenoterol, (R,R')-, (S,S')-,
      (R,S')-, and (S,R')-fenoterol, to the beta(2)-adrenergic receptor (beta(2)-AR)
      have been determined. The experiments utilized membranes obtained from HEK cells
      stably transfected with cDNA encoding human beta(2)-AR. Competitive displacement
      studies using [(3)H]CGP-12177 as the marker ligand were conducted at 4, 15, 25,
      30 and 37 degrees C, the binding affinities calculated and the standard enthalpic
      (DeltaH degrees ) and standard entropic (DeltaS degrees ) contribution to the
      standard free energy change (DeltaG degrees ) associated with the binding process
      determined through the construction of van't Hoff plots. The results indicate
      that the binding of (S,S')- and (S,R')-fenoterol were predominately enthalpy
      driven processes while the binding of (R,R')- and (R,S')-fenoterol were entropy
      driven. All of the fenoterol stereoisomers are full agonists of the beta(2)-AR,
      and, therefore, the results of this study are inconsistent with the previously
      described "thermodynamic agonist-antagonist discrimination", in which the binding
      of an agonist to the beta-AR is entropy-driven and the binding of an antagonist
      is enthalpy-driven. In addition, the data demonstrate that the chirality of the
      carbon atom containing the beta-hydroxyl group of the fenoterol molecule (the
      beta-OH carbon) is a key factor in the determination of whether the binding
      process will be enthalpy-driven or entropy-driven. When the configuration at the
      beta-OH carbon is S the binding process is enthalpy-driven while the R
      configuration produces an entropy-driven process.

PMID- 20144592
TI  - Timed changes of synaptic zinc, synaptophysin and MAP2 in medial extended
      amygdala of epileptic animals are suggestive of reactive neuroplasticity.
AB  - Repeated seizures induce permanent alterations of the brain in experimental
      models and patients with intractable temporal lobe epilepsy (TLE), which is a
      common form of epilepsy in humans. Together with cell loss and gliosis in many
      brain regions, synaptic reorganization is observed principally in the
      hippocampus. However, in the amygdala this synaptic reorganization has been not
      studied. The changes in Zn density, synaptophysin and MAP(2) as markers of
      reactive synaptogenesis in medial extended amygdala induced by kainic acid (KA)
      as a model of TLE was studied. Adult male rats (n=6) were perfused at 10 days, 1,
      2, 3 and 4 months after KA i.p. injection (9 mg/kg). Controls were injected with
      saline. The brains were processed by the Timm's method to reveal synaptic Zn and
      analyzed by densitometry. Immunohistochemistry was used to reveal synaptophysin
      and MAP(2) expression. A two-way ANOVA was used for statistics, with a P<0.05 as
      a significance limit. Normal dark staining was seen in all medial extended
      amygdala subdivisions of control animals. At 10 days post KA injection a dramatic
      loss of staining was observed. A slow but steady recovery of Zn density can be
      followed in the 4 month period studied. Parallel, from 10 days to 2 months
      stronger synaptophysin expression could be observed, whereas MAP(2) expression
      increased from 1 month with peak levels at 3-4 months. The results suggest that a
      process of sprouting exists in surviving neurons of medial extended amygdala
      after status epilepticus and that these neurons might be an evidence of a
      reactive synaptogenesis process.

PMID- 20144593
TI  - Synthesis and evaluation of novel analogues of vitamin B6 as reactivators of
      tabun and paraoxon inhibited acetylcholinesterase.
AB  - A series of novel pyridinium oximes was prepared by reactions of quaternization
      of pyridoxal oxime with substituted phenacyl bromides in acetone at room
      temperature. The structures of compounds were determined according to the data
      obtained by IR spectroscopy, mass spectrometry, (1)H and (13)C nuclear magnetic
      resonance spectroscopy as well as by elemental analysis. We tested pyridoxal
      oxime (1) and five prepared oximes in 1mM concentration as reactivators of human
      erythrocytes acetylcholinesterase (AChE) inhibited by organophosphorus compounds
      tabun and paraoxon: 1-phenacyl-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2
      methylpyridinium bromide (2), 1-(4'-chlorophenacyl)-3-hydroxy-4
      hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (3), 1-(4'
      fluorophenacyl)-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium
      bromide (4), 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-(4'
      methylphenacyl)pyridinium bromide (5), 3-hydroxy-4-hydroxyiminomethyl-5
      hydroxymethyl-2-methyl-1-(4'-methoxyphenacyl)pyridinium bromide (6). However,
      tested oximes were not efficient in reactivation of either tabun or paraoxon
      inhibited AChE. The maximum restored enzyme activity in 24h was below 25%.
      Therefore, this class of compounds cannot be considered as potential improvement
      in a search for new and more efficient antidotes against OP poisoning.

PMID- 20144594
TI  - Factors determining sensitivity or resistance of tumor cell lines towards
      artesunate.
AB  - Clinical oncology is still challenged by the development of drug resistance of
      tumors that result in poor prognosis for patients. There is an urgent necessity
      to understand the molecular mechanisms of resistance and to develop novel therapy
      strategies. Artesunate (ART) is an anti-malarial drug, which also exerts profound
      cytotoxic activity towards cancer cells. We first applied a gene-hunting approach
      using cluster and COMPARE analyses of microarray-based transcriptome-wide mRNA
      expression profiles. Among the genes identified by this approach were genes from
      diverse functional groups such as structural constituents of ribosomes (RPL6,
      RPL7, RPS12, RPS15A), kinases (CABC1, CCT2, RPL41), transcriptional and
      translational regulators (SFRS2, TUFM, ZBTB4), signal transducers (FLNA), control
      of cell growth and proliferation (RPS6), angiogenesis promoting factors (ITGB1),
      and others (SLC25A19, NCKAP1, BST1, DBH, FZD7, NACA, MTHFD2). Furthermore, we
      applied a candidate gene approach and tested the role of resistance mechanisms
      towards established anti-cancer drugs for ART resistance. By using transfected or
      knockout cell models we found that the tumor suppressor p16(INK4A) and the anti
      oxidant protein, catalase, conferred resistance towards ART, while the oncogene
      HPV-E6 conferred sensitivity towards ART. The tumor suppressor p53 and its
      downstream protein, p21, as well as the anti-oxidant manganese-dependent
      superoxide dismutase did not affect cellular response to ART. In conclusion, our
      pharmacogenomic approach revealed that response of tumor cells towards ART is
      multi-factorial and is determined by gene expression associated with either ART
      sensitivity or resistance. At least some of the functional groups of genes (e.g.
      angiogenesis promoting factors, cell growth and proliferation-associated genes
      signal transducers and kinases) are also implicated in clinical responsiveness of
      tumors towards chemotherapy. It merits further investigation, whether ART is
      responsive in clinically refractory tumors and whether the genes identified in
      the present study also determine clinical responsiveness towards ART.

PMID- 20144595
TI  - The impact of osteopontin promoter polymorphisms on the risk of calcium
      urolithiasis.
AB  - BACKGROUND: Osteopontin (OPN) is an important modulator of urolithiasis
      formation. Three functional polymorphisms (-66T/G, -156delG/G, and -443T/G) on
      the promoter region of the OPN gene have been found to affect the gene expression
      and transcriptional activity. This study investigated the association of those
      three functional polymorphisms with the risk of calcium urolithiasis. METHODS: A
      total of 249 cases diagnosed with calcium urolithiasis and 247 age- and sex
      matched healthy controls were recruited from Kaohsiung Medical University
      Hospital between June, 2003 and February, 2007. All subjects completed a detailed
      questionnaire survey, and provided blood and urine samples for biochemical
      evaluations. Three single nucleotide polymorphisms were determined by using
      TaqMan 5' allelic discrimination assay. RESULTS: In-156delG/G polymorphism,
      subjects who carried delG allele had a significantly higher risk of developing
      calcium urolithiasis than those with G allele (odds ratio=1.39; 95% confidence
      interval=1.02-1.90; P=0.037). In stone cases, subjects with delG/G and delG/delG
      genotypes also had significantly higher urinary ratio of calcium to OPN than
      those with G/G genotype (11.8+/-15.9 vs 7.08+/-5.26, P=0.021). CONCLUSIONS: The 
      156 delG/G polymorphism of OPN gene could serve as a candidate genetic marker
      used to evaluate the risk of calcium urolithiasis.

PMID- 20144596
TI  - Moderate phenotypic expression of familial hypercholesterolemia in Tunisia.
AB  - BACKGROUND: Autosomal Dominant Hypercholesterolemia (ADH) is an autosomal
      dominant disease caused by mutations in the low density lipoprotein receptor
      (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type
      9 (PCSK9) genes. Xanthomas and coronary heart diseases (CHD) at an early age are
      the major clinical manifestations of the disease. METHODS: 16 families with
      familial hypercholesterolemia from different regions in Tunisia participated in
      the study. Mutations within the LDLR gene were screened through DNA sequencing.
      Lipids values were measured by standard enzymatic methods. RESULTS: We present
      here thirty five homozygotes and fifty six heterozygotes. Homozygotes presented
      extensive xanthomatosis, variable clinical manifestations of CHD, and total
      cholesterol levels in males and females of 17.26+/-4.18 and 17.64+/-2.59 mmol/L
      respectively. HDL-cholesterol levels were 0.62+/-0.24 and 1.00+/-0.61 mmol/L for
      males and females, respectively. None of the heterozygotes had tendon xanthomas
      (except for one female aged 62), eight had corneal arcus, and nine developed CHD
      mean between 46 and 88 years old. Total cholesterol levels in males and females
      ranged from 4.60 to 8.90 and from 4.30 to 10.50 mmol/L, respectively. CONCLUSION:
      Tunisian FH heterozygotes are characterized by a moderate clinical and biological
      expression of the disease.

PMID- 20144597
TI  - The genetic association of vitamin D receptor polymorphisms and cervical
      spondylotic myelopathy in Chinese subjects.
AB  - BACKGROUND: The association of vitamin D receptor (VDR) gene polymorphisms to the
      lumbar degenerative disc disease has been previously studied; however, the role
      of VDR gene polymorphisms in cervical spondylosis remains unknown. METHODS: One
      hundred fifty four patients with cervical spondylotic myelopathy (CSM) and 156
      controls were enrolled. The clinical characteristics were collected and the
      severity of cervical spondylotic myelopathy was evaluated by magnetic resonance
      imaging (MRI). The VDR polymorphism genotyping was performed. RESULTS: No
      significant difference in clinical characteristics was noted between the case and
      controls. For ApaI polymorphism, the cases had a marked higher prevalence of AA
      genotype (19.5% vs. 8.3%, P=0.003) and A allele frequencies (34.4% vs. 22.4%,
      P<0.001) than controls. For TaqI polymorphism, the cases had a significant higher
      prevalence of TT genotype (67.5 vs. 44.2%, P<0.001) and T allele frequencies
      (76.9% vs. 54.2%, P<0.001) than controls. The odds ratio for CSM was 2.88 for the
      ApaI A allele carriers and 4.67 for the TaqI T allele carriers. The TaqI
      genotypes, both TT and TC showed a markedly higher MRI severity grading level
      than CC genotype (both P<0.01, compared with CC genotype). CONCLUSION: Certain
      VDR polymorphism is related in the presence and severity of CSM in Chinese
      subjects.

PMID- 20144598
TI  - Mutation -538 T/C in bone morphogenetic protein 4 do not increase the risk in
      sickle-cell disease with orthopedic complications but strongly associated with
      increased LDH and uric acid level in Indian patients from Chhattisgarh and
      Jharkhand states.
AB  - BACKGROUND: Bone morphogenetic protein (BMP) are involved in the various
      orthopedic complications such as avascular necrosis, osteonecrosis and bone
      turnover, therefore genes coding for proteins, like BMP4, can be potential
      candidate for studying orthopedic disorders. METHODS: A case-control study was
      conducted to examine the association between SNP T538C of BMP4 and orthopedic
      complications in sickling patients by employing PCR-RFLP. RESULTS: A total of 200
      cases and 172 control groups were studied from Indian population. T538C SNP has
      not been implicated in disease and doesn't increase the risk (OR=0.89, OR=0.68).
      We observed no significant association between the T538C polymorphism and case
      group in the studied population. However, we observed significantly increased
      uric acid and LDH level in homowild (TT), heteromutant (TC) and homomutant (CC)
      in case group compared to control group ( all p=0.0001) and (p=0.0001, p=0.0001,
      p=0.015 and p=0.0001, p=0.0001, p=0.0001 respectively) in the studied population.
      CONCLUSIONS: The T/C polymorphism in BMP4 is not associated with case group and
      in view of present observation, we suggest that evaluation of LDH and uric acid
      level and its association with polymorphisms in the BMP4 may be considered to be
      reliable molecular and biochemical markers, and possess promising rational for
      diagnostic potential in clinical cases.

PMID- 20144599
TI  - Insulin resistance in early untreated rheumatoid arthritis patients.
AB  - OBJECTIVES: To assess insulin resistance in early untreated rheumatoid arthritis
      patients and its relation to the clinical, inflammatory and biochemical
      characteristics of these patients. PATIENTS AND METHODS: Sixty-six untreated
      rheumatoid arthritis (RA) patients with disease duration less than 1 year along
      with age and sex matched controls were studied. Disease activity score (DAS28)
      was used to assess disease activity. Plasma levels of C- reactive protein (CRP),
      glucose, insulin and complete lipid profile were measured. Insulin resistance
      (IR) was estimated by the homeostasis model assessment for insulin resistance
      (HOMA-IR). RESULTS: RA patients revealed high grade systemic inflammation
      compared to control group p<0.0001. Patients with high disease activity were more
      insulin resistant than patients with moderate disease activity P<0.0001.
      CONCLUSION: The findings of the present study showed that early untreated RA
      patients are characterized by a severe insulin resistant state that is driven
      primarily by disease activity and systemic inflammation.

PMID- 20144600
TI  - The TCN2 776CNG polymorphism correlates with vitamin B(12) cellular delivery in
      healthy adult populations.
AB  - OBJECTIVES: Vitamin B(12), or B(12), is an essential nutrient for humans, and its
      deficiency is a public health problem, especially in elderly population. Around
      30% of circulating total B(12) levels are attached to transcobalamin II (TCN2),
      being referred as holotranscobalamin (holo-TC), and representing the biologically
      active fraction. After cellular uptake, B(12) participates in the homocysteine
      (Hcy) metabolism. The potential influence of the described TCN2 776CNG
      polymorphism upon B(12) intracellular delivery is a current target of research
      and we aimed to investigate its biochemical significance upon a healthy adult
      population. DESIGN AND METHODS: The TCN2 776CNG polymorphism was screened by PCR
      RFLP in 122 individuals. Concentrations of plasma total B(12), holo-TC, total Hcy
      and folate, as well as red blood cell folate, were determined. RESULTS AND
      CONCLUSIONS: The studied polymorphism is common in the Portuguese population and
      significantly affects holo-TC but neither total B(12) nor total Hcy plasma
      concentrations, confirming that the TCN2 776CNG genotype exerts a significant
      influence upon B(12) cellular delivery.

PMID- 20144601
TI  - Development of a high-resolution melting method for the detection of hemoglobin
      alpha variants.
AB  - OBJECTIVES: The present study was aimed at identifying hemoglobin (Hb) alpha
      variants. DESIGN AND METHODS: To identify Hb variants, a high-resolution melting
      (HRM) method was performed. RESULTS: The diagnostic strategy was found to be
      successful in identifying Hb alpha variants including HBA1:c.27G>T, (Hb Hekinan)
      HBA1:c.46G>C (Hb Ottawa), HBA2:c.31_33AG (Hb alpha2-globin gene codon del AG),
      HBA1:c.223G>C (Hb G-Taichung), HBA1:p.Phe118_Thr119insIle (Hb Phnom Penh),
      HBA2:c.369C>G (Hb Westmead), HBA2:c.364G>A (or HBA1) (Hb Owari), HBA2:c.377T>C
      (Hb Quong Sze), and HBA2:c.427T>C (Hb Constant Spring). Each Hb variant could be
      readily and easily identified through the difference in plotted curves. In
      addition, the Hb variants could be distinguished to be located at either HBA1 or
      HBA2 gene. CONCLUSIONS: The HRM analysis is found to be a good tool for
      identifying Hb variants in alpha globin genes.

PMID- 20144602
TI  - Phosphorylation of Junb family proteins by the Jun N-terminal kinase supports
      tissue regeneration in zebrafish.
AB  - Tissue regeneration is fundamental for multi-cellular organisms to maintain their
      integrity, but the competence of tissue restoration is different depending on
      tissues, species, and ages. In spite of the recent progresses of the molecular
      basis of regeneration, little is known about its regulative processes. We
      previously identified the junb and junb-like (junbl) as transcripts induced in
      response to tissue injury in zebrafish. It has been demonstrated that the
      mammalian JunB is not phosphorylated by the Jun N-terminal kinase (JNK) due to
      the absence of a target site. Here, we show that the zebrafish Junb proteins
      retain the target site and are phosphorylated by the JNK. Significantly, we found
      that the phosphorylated Junb proteins (pJunbs) are necessary for adult and larval
      tissue regeneration, suggesting that the regulation of Junb proteins by
      phosphorylation is one of the molecular bases for the higher regeneration ability
      in zebrafish. We also show that the prolonged expression of junbs and their
      protein phosphorylation by the JNK after the wound healing stage are the unique
      and necessary features for regeneration. Thus, our data suggest that the
      transcriptional and post-transcriptional controls of junbs and their protein
      products are the important regulative steps that enable tissue regeneration in
      zebrafish.

PMID- 20144603
TI  - Replacement of mouse Sox10 by the Drosophila ortholog Sox100B provides evidence
      for co-option of SoxE proteins into vertebrate-specific gene-regulatory networks
      through altered expression.
AB  - Neural crest cells and oligodendrocytes as the myelinating glia of the central
      nervous system exist only in vertebrates. Their development is regulated by
      complex regulatory networks, of which the SoxE-type high-mobility-group domain
      transcription factors Sox8, Sox9 and Sox10 are essential components. Here we
      analyzed by in ovo electroporation in chicken and by gene replacement in the
      mouse whether the Drosophila ortholog Sox100B can functionally substitute for
      vertebrate SoxE proteins. Sox100B overexpression in the chicken neural tube led
      to the induction of neural crest cells as previously observed for vertebrate SoxE
      proteins. Furthermore, many aspects of neural crest and oligodendrocyte
      development were surprisingly normal in mice in which the Sox10 coding
      information was replaced by Sox100B arguing that Sox100B integrates well into the
      gene-regulatory networks that drive these processes. Our results therefore
      provide strong evidence for a model in which SoxE proteins were co-opted to these
      gene-regulatory networks mainly through the acquisition of novel expression
      patterns. However, later developmental defects in several neural crest derived
      lineages in mice homozygous for the Sox100B replacement allele indicate that some
      degree of functional specialization and adaptation of SoxE protein properties
      have taken place in addition to the co-option event.

PMID- 20144604
TI  - Postgastrular zen expression is required to develop distinct amniotic and serosal
      epithelia in the scuttle fly Megaselia.
AB  - The amnioserosa is an extraembryonic epithelium that evolved in higher
      cyclorrhaphan flies from distinct serosal and amniotic epithelia. The underlying
      genetic mechanism of this evolutionary transition is unknown. Amnioserosa
      development of Drosophila correlates with novel expression characteristics of the
      homeobox gene zerknullt (zen), including a broad zen expression domain in the
      syncytial blastoderm and the complete absence of postgastrular zen expression.
      Here we examine the functional significance of these features by altering the
      activity profile of zen in Megaselia (a lower cyclorrhaphan fly with distinct
      serosal and amniotic epithelia) and Drosophila, and by examining in Megaselia the
      function of u-shaped group (ush-group) genes, which in Drosophila maintain the
      amnioserosa after gastrulation when zen is no longer expressed. In Megaselia,
      loss of postgastrular zen expression abrogates serosa development but allows
      amnion development. Ectopic expression of zen in early Megaselia embryos allows
      serosa formation but perturbs amnion development. Megaselia homologues of u
      shaped group genes are not essential for serosa formation but mediate germband
      retraction and dorsal closure. Finally, ectopic postgastrular zen expression in
      Drosophila causes an enlargement of amnioserosa cells and interferes with the
      morphogenetic functions of the amnioserosa. Our results suggest that the origin
      of the amnioserosa involved the loss of postgastrular zen expression from
      extraembryonic tissue, that the early broad expression domain of Drosophila zen
      evolved afterwards, and that the ush-group genes ancestrally played a role in
      morphogenetic functions of the amnion.

PMID- 20144605
TI  - Dicer is required for survival of differentiating neural crest cells.
AB  - The neural crest (NC) lineage gives rise to a wide array of cell types ranging
      from neurons and glia of the peripheral nervous system to skeletal elements of
      the head. The mechanisms regulating NC differentiation into such a large number
      of cell types remain largely unknown. MicroRNAs (miRNAs) play key roles in
      regulating developmental events suggesting they may also play a role during NC
      differentiation. To determine what roles miRNAs play in differentiation of NC
      derived tissues, we deleted the miRNA processing gene Dicer in NC cells using the
      Wnt1-Cre deleter line. We show that deletion of Dicer soon after NC cells have
      formed does not affect their migration and colonization of their targets in the
      embryo. However, the post-migratory NC is dependent on Dicer for survival. In the
      head, loss of Dicer leads to a loss of NC-derived craniofacial bones while in the
      trunk, cells of the enteric, sensory and sympathetic nervous systems are lost
      during development. We found that loss of Dicer does not prevent the initial
      differentiation of NC but as development progresses, NC derivatives are lost due
      to apoptotic cell death. When Dicer is deleted, both Caspase-dependent and 
      independent apoptotic pathways are activated in the sensory ganglia but only the
      Caspase-dependent apoptotic program was activated in the sympathetic nervous
      system showing that the specific endogenous apoptotic programs are turned on by
      loss of Dicer. Our results show that Dicer and miRNAs, are required for survival
      of NC-derived tissues by preventing apoptosis during differentiation.

PMID- 20144607
TI  - The regulation of Dkk1 expression during embryonic development.
AB  - During embryogenesis, the Dkk1 mediated Wnt inhibition controls the
      spatiotemporal dynamics of cell fate determination, cell differentiation and cell
      death. Furthermore, the Dkk1 dose is critical for the normal Wnt homeostasis, as
      alteration of the Dkk1 activity is associated with various diseases. We
      investigated the regulation of Dkk1 expression during embryonic development. We
      identified nine conserved non-coding elements (CNEs), located 3' to the Dkk1
      locus. Analyses of the regulatory potential revealed that four of these CNEs in
      combination drive reporter expression very similar to Dkk1 expression in several
      organs of transgenic embryos. We extended the knowledge of Dkk1 expression during
      hypophysis, external genitalia and kidney development, suggesting so far to
      unexplored functions of Dkk1 during the development of these organs.
      Characterization of the regulatory potential of four individual CNEs revealed
      that each of these promotes Dkk1 expression in brain and kidney. In combination,
      two enhancers are responsible for expression in the pituitary and the genital
      tubercle. Furthermore, individual CNEs mediates craniofacial, optic cup and limb
      specific Dkk1 regulation. Our study substantially improves the knowledge of Dkk1
      regulation during embryonic development and thus might be of high relevance for
      therapeutic approaches.

PMID- 20144606
TI  - Neurog2 controls the leading edge of neurogenesis in the mammalian retina.
AB  - In the mammalian retina, neuronal differentiation begins in the dorso-central
      optic cup and sweeps peripherally and ventrally. While certain extrinsic factors
      have been implicated, little is known about the intrinsic factors that direct
      this process. In this study, we evaluate the expression and function of proneural
      bHLH transcription factors during the onset of mouse retinal neurogenesis. Dorso
      central retinal progenitor cells that give rise to the first postmitotic neurons
      express Neurog2/Ngn2 and Atoh7/Math5. In the absence of Neurog2, the spread of
      neurogenesis stalls, along with Atoh7 expression and RGC differentiation.
      However, neurogenesis is eventually restored, and at birth Neurog2 mutant retinas
      are reduced in size, with only a slight increase in the retinal ganglion cell
      population. We find that the re-establishment of neurogenesis coincides with the
      onset of Ascl1 expression, and that Ascl1 can rescue the early arrest of neural
      development in the absence of Neurog2. Together, this study supports the
      hypothesis that the intrinsic factors Neurog2 and Ascl1 regulate the temporal
      progression of retinal neurogenesis by directing overlapping waves of neuron
      formation.

PMID- 20144609
TI  - Cis-regulatory characterization of sequence conservation surrounding the Hox4
      genes.
AB  - Hox genes are key regulators of anterior-posterior axis patterning and have a
      major role in hindbrain development. The zebrafish Hox4 paralogs have strong
      overlapping activities in hindbrain rhombomeres 7 and 8, in the spinal cord and
      in the pharyngeal arches. With the aim to predict enhancers that act on the
      hoxa4a, hoxb4a, hoxc4a and hoxd4a genes, we used sequence conservation around the
      Hox4 genes to analyze all fish:human conserved non-coding sequences by reporter
      assays in stable zebrafish transgenesis. Thirty-four elements were functionally
      tested in GFP reporter gene constructs and more than 100 F1 lines were analyzed
      to establish a correlation between sequence conservation and cis-regulatory
      function, constituting a catalog of Hox4 CNEs. Sixteen tissue-specific enhancers
      could be identified. Multiple alignments of the CNEs revealed paralogous cis
      regulatory sequences, however, the CNE sequence similarities were found not to
      correlate with tissue specificity. To identify ancestral enhancers that direct
      Hox4 gene activity, genome sequence alignments of mammals, teleosts, horn shark
      and the cephalochordate amphioxus, which is the most basal extant chordate
      possessing a single prototypical Hox cluster, were performed. Three elements were
      identified and two of them exhibited regulatory activity in transgenic zebrafish,
      however revealing no specificity. Our data show that the approach to identify cis
      regulatory sequences by genome sequence alignments and subsequent testing in
      zebrafish transgenesis can be used to define enhancers within the Hox clusters
      and that these have significantly diverged in their function during evolution.

PMID- 20144610
TI  - Anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on
      retinal ganglion cells after optic nerve crush are PI3K/AKT-dependent.
AB  - The purpose of present study is to dissect the role of PI3K/AKT signaling in the
      anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on
      rat retinal ganglion cells (RGCs) after optic nerve (ON) crush. The ONs of
      seventy-two adult male Wistar rats were crushed by a standardized method. Control
      eyes received a sham operation. G-CSF or phosphate-buffered saline (PBS) was
      immediately administrated after the ON event for 5 days. Twelve rats were used to
      investigate the signaling pathways using western blot analysis. In other sixty
      rats, each eye also received intravitreal injections of PI3K/AKT inhibitor
      (LY294002) or PBS immediately after the experiments. Rats were euthanized at 1 or
      2 weeks after the experiment. RGC density was counted by retrograde labeling with
      Fluorogold. Western blot analysis of p-AKT, TUNEL assays, and
      immunohistochemistry of the retinas were conducted. Two weeks after ON injury,
      RGC densities in the central and mid-peripheral retinas of ON-crushed, G-CSF
      treated rats were significantly higher than those of corresponding ON-crushed, G
      CSF-treated and LY294002-injected rats (survival rates of 60% vs. 39% and 43% vs.
      33%, respectively; p < 0.01). Decreased TUNEL staining and the up-regulations of
      p-AKT signaling in retinas of ON-crushed, G-CSF-treated rats were blocked by
      intravitreal injections of LY294002. The double staining showed that p-AKT
      expression co-localized with RGCs in the ON crushed, G-CSF treated retinas. In
      conclusion, the anti-apoptotic effects of G-CSF on RGCs are PI3K/AKT signaling
      dependent in the retinas to rescue RGCs after ON crush injury.

PMID- 20144608
TI  - Targeted deletion of Hand2 in cardiac neural crest-derived cells influences
      cardiac gene expression and outflow tract development.
AB  - The basic helix-loop-helix DNA binding protein Hand2 has critical functions in
      cardiac development both in neural crest-derived and mesoderm-derived structures.
      Targeted deletion of Hand2 in the neural crest has allowed us to genetically
      dissect Hand2-dependent defects specifically in outflow tract and cardiac cushion
      independent of Hand2 functions in mesoderm-derived structures. Targeted deletion
      of Hand2 in the neural crest results in misalignment of the aortic arch arteries
      and outflow tract, contributing to development of double outlet right ventricle
      (DORV) and ventricular septal defects (VSD). These neural crest-derived
      developmental anomalies are associated with altered expression of Hand2-target
      genes we have identified by gene profiling. A number of Hand2 direct target genes
      have been identified using ChIP and ChIP-on-chip analyses. We have identified and
      validated a number of genes related to cell migration, proliferation/cell cycle
      and intracellular signaling whose expression is affected by Hand2 deletion in the
      neural crest and which are associated with development of VSD and DORV. Our data
      suggest that Hand2 is a multifunctional DNA binding protein affecting expression
      of target genes associated with a number of functional interactions in neural
      crest-derived cells required for proper patterning of the outflow tract,
      generation of the appropriate number of neural crest-derived cells for elongation
      of the conotruncus and cardiac cushion organization. Our genetic model has made
      it possible to investigate the molecular genetics of neural crest contributions
      to outflow tract morphogenesis and cell differentiation.

PMID- 20144612
TI  - Physiological mechanism of homing migration in Pacific salmon from behavioral to
      molecular biological approaches.
AB  - The amazing abilities of Pacific salmon to migrate long distances from the ocean
      to their natal streams for spawning have been investigated intensively since
      1950's, but there are still many mysteries because of difficulties to follow
      their whole life cycle and to wait their sole reproductive timing for several
      years. In my laboratory, we have tried to clarify physiological mechanisms of
      homing migration in Pacific salmon, using four anadromous Pacific salmon (pink,
      Oncorhynchus gorbuscha; chum, Oncorhynchus keta; sockeye, Oncorhynchus nerka;
      masu, Oncorhynchus masou) in the north Pacific Ocean as well as two lacustrine
      salmon (sockeye and masu) in Lake Toya and Lake Shikotsu, Hokkaido, Japan, where
      the lakes serve as a model "ocean". Three different approaches from behavioral to
      molecular biological researches have been conducted using these model fish.
      First, the homing behaviors of adult chum salmon from the Bering Sea to Hokkaido
      as well as lacustrine sockeye and masu salmon in Lake Toya were examined by means
      of physiological biotelemetry techniques, and revealed that salmon can navigate
      in open water using different sensory systems. Second, the hormone profiles in
      the brain-pituitary-gonadal (BPG) axis were investigated in chum salmon and
      lacustrine sockeye salmon during their homing migration by means of hormone
      specific time-resolved fluoroimmunoassay (TR-FIA) systems, and clarified that
      salmon gonadotropin-releasing hormone (sGnRH) plays leading roles on homing
      migration. Third, the olfactory functions of salmon were studied by means of
      electrophysiological, behavioral, and molecular biological techniques, and made
      clear that olfactory discriminating ability of natal stream odors. These results
      have discussed with the evolutional aspects of four Pacific salmon, sexual
      differences in homing profiles, and the possibility of dissolved free amino acids
      (DFAA) as natal stream odors for salmon.

PMID- 20144614
TI  - Analysis of Cry8Ka5-binding proteins from Anthonomus grandis (Coleoptera:
      Curculionidae) midgut.
AB  - Biotech crops expressing Bacillus thuringiensis Cry toxins present a valuable
      approach for insect control. Cry8Ka5, which is highly toxic to the cotton boll
      weevil (Anthonomus grandis), was used as a model to study toxin-ligand
      interactions. Three Cry-binding proteins were detected after toxin overlay
      assays. Following de novo sequencing, a heat-shock cognate protein and a V-ATPase
      were identified, whilst a approximately 120 kDa protein remained unknown.
      Additional Cry8Ka5-binding proteins were visualized by two-dimensional gel
      electrophoresis ligand blots.

PMID- 20144613
TI  - 17beta-Estradiol levels in male zebra finch brain: combining Palkovits punch and
      an ultrasensitive radioimmunoassay.
AB  - Local aromatization of testosterone into 17beta-estradiol (E(2)) is often
      required for the physiological and behavioral actions of testosterone. In most
      vertebrates, aromatase is expressed in a few discrete brain regions. While many
      studies have measured brain aromatase mRNA or activity, very few studies have
      measured brain E(2) levels, particularly in discrete brain regions, because of
      technical challenges. Here, we used the Palkovits punch technique to isolate 13
      discrete brain nuclei from adult male zebra finches. Steroids were extracted via
      solid phase extraction. E(2) was then measured with an ultrasensitive, specific
      and precise radioimmunoassay. Our protocol leads to high recovery of E(2) (84%)
      and effectively removes interfering brain lipids. E(2) levels were high in
      aromatase-rich regions such as caudal medial nidopallium and hippocampus. E(2)
      levels were intermediate in the medial preoptic area, ventromedial nucleus of the
      hypothalamus, lateral and medial magnocellular nuclei of anterior nidopallium,
      nucleus taeniae of the amygdala, and Area X. E(2) levels were largely non
      detectable in the cerebellum, HVC, lateral nidopallium and optic lobes.
      Importantly, E(2) levels were significantly lower in plasma than in the caudal
      medial nidopallium. This protocol allows one to measure E(2) in discrete brain
      regions and potentially relate local E(2) concentrations to aromatase activity
      and behavior.

PMID- 20144615
TI  - Cardiomyocyte-targeted overexpression of the coxsackie-adenovirus receptor causes
      a cardiomyopathy in association with beta-catenin signaling.
AB  - The coxsackie-adenovirus receptor (CAR) is an adhesion molecule found at the
      intercalated disc of cardiomyocytes in association with other adherens and tight
      junction proteins. CAR expression is increased at cardiomyocyte junctions in
      patients with heart failure. It is not known what contribution elevated CAR
      expression makes to cardiac pathology. We generated a binary transgenic mouse
      enabling cardiac-restricted doxycycline-regulated expression of Flag-tagged
      murine CAR (mCAR(+)/alpha MtTA(+) mice). Myocardial CAR levels were increased 6
      fold in mCAR(+)/alpha MtTA(+) mice, localizing to intercalated discs and
      sarcolemma. Well at birth, mCAR(+)/alpha MtTA(+) mice developed a severe
      cardiomyopathy and died by 4 weeks. Cardiomyocyte hypertrophy was evident at 1
      week, with increased heart:body weight ratios by 3 weeks. Disorganization and
      degeneration of cardiomyocytes were evident with disrupted adherens junctions.
      Doxycycline administration turned off transgene expression and rescued mice from
      the development of the cardiomyopathic phenotype. In CAR-overexpressing
      mCAR(+)/alpha MtTA(+) mice, adherens junction proteins were abnormally expressed.
      N-cadherin protein levels were 83% lower in mCAR(+)/alpha MtTA(+) hearts vs
      controls at 1 week, with levels subsequently increased above controls at 3 weeks.
      beta-catenin expression was 90% and 135% above controls at 1 and 3 weeks,
      respectively. Nuclear translocation of beta-catenin in cardiomyocytes of
      mCAR(+)/alpha MtTA(+) mice was associated with increased c-myc RNA, a target of
      active beta-catenin known to be associated with cardiac hypertrophy. Our study is
      the first to demonstrate that increased CAR expression can induce a
      cardiomyopathy and supports a model whereby the pathogenesis is determined by CAR
      stimulated beta-catenin signaling, and/or disruption of the adherens junction.

PMID- 20144616
TI  - The critical role of intracellular zinc in adenosine A(2) receptor activation
      induced cardioprotection against reperfusion injury.
AB  - Exogenous zinc can protect cardiac cells from reperfusion injury, but the exact
      roles of endogenous zinc in the pathogenesis of reperfusion injury and in
      adenosine A(2) receptor activation-induced cardioprotection against reperfusion
      injury remain unknown. Adenosine A(1)/A(2) receptor agonist 5'-(N
      ethylcarboxamido) adenosine (NECA) given at reperfusion reduced infarct size in
      isolated rat hearts subjected to 30min ischemia followed by 2h of reperfusion.
      This effect of NECA was partially but significantly blocked by the zinc chelator
      N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), and ZnCl(2) given at
      reperfusion mimicked the effect of NECA by reducing infarct size. Total tissue
      zinc concentrations measured with inductively coupled plasma optical emission
      spectroscopy (ICPOES) were decreased upon reperfusion in rat hearts and this was
      reversed by NECA. NECA increased intracellular free zinc during reperfusion in
      the heart. Confocal imaging study showed a rapid increase in intracellular free
      zinc in isolated rat cardiomyocytes treated with NECA. Further experiments
      revealed that NECA increased total zinc levels upon reperfusion in mitochondria
      isolated from isolated hearts. NECA attenuated mitochondrial swelling upon
      reperfusion in isolated hearts and this was inhibited by TPEN. Similarly, NECA
      prevented the loss of mitochondrial membrane potential (DeltaPsim) caused by
      oxidant stress in cardiomyocytes. Finally, both NECA and ZnCl(2) inhibited the
      mitochondrial metabolic activity. NECA-induced cardioprotection against
      reperfusion injury is mediated by intracellular zinc. NECA prevents reperfusion
      induced zinc loss and relocates zinc to mitochondria. The inhibitory effects of
      zinc on both the mPTP opening and the mitochondrial metabolic activity may
      account for the cardioprotective effect of NECA.

PMID- 20144617
TI  - Cardiac spectrins: alternative splicing encodes functional diversity.

PMID- 20144618
TI  - Protein vivisection reveals elusive intermediates in folding.
AB  - Although most folding intermediates escape detection, their characterization is
      crucial to the elucidation of folding mechanisms. Here, we outline a powerful
      strategy to populate partially unfolded intermediates: A buried aliphatic residue
      is substituted with a charged residue (e.g., Leu-->Glu(-)) to destabilize and
      unfold a specific region of the protein. We applied this strategy to ubiquitin,
      reversibly trapping a folding intermediate in which the beta5-strand is unfolded.
      The intermediate refolds to a native-like structure upon charge neutralization
      under mildly acidic conditions. Characterization of the trapped intermediate
      using NMR and hydrogen exchange methods identifies a second folding intermediate
      and reveals the order and free energies of the two major folding events on the
      native side of the rate-limiting step. This general strategy may be combined with
      other methods and have broad applications in the study of protein folding and
      other reactions that require trapping of high-energy states.

PMID- 20144619
TI  - Thresholds in transient dynamics of signal transduction pathways.
AB  - Transient dynamics of signal transduction pathways play an important role in many
      biological processes, including cell differentiation, apoptosis, metabolism and
      DNA damage response. Recent examples of quantitative methods to characterize
      transient signals include transient metabolic control coefficients and finite
      time Lyapunov exponents. In our work we compare these quantitative methods to
      characterize transient phenomena and specifically discuss their predictive power
      for three examples. We focus on the identification of thresholds that separate
      different transient dynamic behaviors. Our investigation leads to the following
      results: The spectrum of the finite-time Lyapunov exponents unambiguously and
      reliably identifies putative thresholds in transient dynamics. Metabolic control
      coefficients do not reliably detect all thresholds and suffer from false
      positives.

PMID- 20144620
TI  - Distributions for negative-feedback-regulated stochastic gene expression:
      dimension reduction and numerical solution of the chemical master equation.
AB  - In this work we introduce a novel approach to study biochemical noise. It
      comprises a simplification of the master equation of complex reaction schemes
      (via an adiabatic approximation) and the numerical solution of the reduced master
      equation. The accuracy of this procedure is tested by comparing its results with
      analytic solutions (when available) and with Gillespie stochastic simulations. We
      further employ our approach to study the stochastic expression of a simple gene
      network, which is subject to negative feedback regulation at the transcriptional
      level. Special attention is paid to the influence of negative feedback on the
      amplitude of intrinsic noise, as well as on the relaxation rate of the system
      probability distribution function to the steady solution. Our results suggest the
      existence of an optimal feedback strength that maximizes this relaxation rate.

PMID- 20144621
TI  - Phase organization of circadian oscillators in extended gate and oscillator
      models.
AB  - The suprachiasmatic nuclei (SCN) control daily oscillations in physiology and
      behavior. The gate-oscillator model captures functional heterogeneity in SCN and
      has been successful in reproducing many features of SCN. This paper investigates
      the mechanism of phase organization in the gate-oscillator model and finds that
      only stable fixed points of the phase transition function are essential to phase
      organization. This obvious finding forms the basis for understanding the complex
      phase distribution in the gate-oscillator scheme. Extending the model with a dead
      zone of the phase transition function and the propagation delay of the gate
      signal which may represent the spatial structure of SCN, the author discusses how
      some features of experimentally reported phase distribution, such as the
      existence of anti-phase neurons and fixed phase difference between neurons, could
      be understood in the framework of the gate-oscillator model. The extended model
      shows clearly the way in which the interplay between the single-cell property and
      the property of the network organization influence the phase distribution of SCN
      neurons.

PMID- 20144622
TI  - Revisiting "The evolution of reciprocity in sizable groups": continuous
      reciprocity in the repeated n-person prisoner's dilemma.
AB  - For many years in evolutionary science, the consensus view has been that while
      reciprocal altruism can evolve in dyadic interactions, it is unlikely to evolve
      in sizable groups. This view had been based on studies which have assumed
      cooperation to be discrete rather than continuous (i.e., individuals can either
      fully cooperate or else fully defect, but they cannot continuously vary their
      level of cooperation). In real world cooperation, however, cooperation is often
      continuous. In this paper, we re-examine the evolution of reciprocity in sizable
      groups by presenting a model of the n-person prisoner's dilemma that assumes
      continuous rather than discrete cooperation. This model shows that continuous
      reciprocity has a dramatically wider basin of attraction than discrete
      reciprocity, and that this basin's size increases with efficiency of cooperation
      (marginal per capita return). Further, we find that assortative interaction
      interacts synergistically with continuous reciprocity to a much greater extent
      than it does with discrete reciprocity. These results suggest that previous
      models may have underestimated reciprocity's adaptiveness in groups. However, we
      also find that the invasion of continuous reciprocators into a population of
      unconditional defectors becomes realistic only within a narrow parameter space in
      which the efficiency of cooperation is close to its maximum bound. Therefore our
      model suggests that continuous reciprocity can evolve in large groups more easily
      than discrete reciprocity only under unusual circumstances.

PMID- 20144624
TI  - RNA interference for therapy in the vascular endothelium.
AB  - RNA interference (RNAi) has become an indispensable tool for loss of function
      analysis in today's basic cell biological research, and is currently being
      utilized for developing novel therapeutic methods. Systemic administration of
      synthetic small interfering RNA (siRNA) into the bloodstream is a feasible route
      for targeting the vascular endothelium or peripheral blood cells. The vascular
      endothelium can be considered an organ by itself, involved in many
      pathophysiological processes. Here, we aim to summarize current strategies of
      using RNAi for analysis of gene function in endothelial (in vitro loss-of
      function analysis) and of exploiting RNAi for therapeutic purposes in order to
      suppress disrupted gene expression ("RNAi therapeutics"). With respect to the
      latter, we will summarize recent experimental concepts as well as ongoing
      therapeutic applications of RNAi mediated suppression of gene expression
      modulating angiogenic processes in cancer and retinopathies. We will further
      discuss the opportunities, prospects, challenges and potential fallbacks as well
      as the present strategies for the realization of "RNAi therapeutics" in combating
      vascular diseases.

PMID- 20144623
TI  - Role of endothelial progenitor cells during ischemia-induced vasculogenesis and
      collateral formation.
AB  - Cell-based therapy has emerged as a promising therapeutic tool for treatment of
      ischemic cardiovascular disease. Both unselected bone marrow-derived mononuclear
      cells (BMNCs), which include stem/progenitor cells and several other cell types,
      and endothelial progenitor cells (EPCs), a subpopulation of BMNCs, display
      regenerative potential in ischemic tissue. Abundant evidence supports the
      involvement of EPCs in capillary growth, and EPCs also appear to participate in
      the formation of collateral vessels. Collectively, these effects have led to
      improved perfusion and functional recovery in animal models of myocardial and
      peripheral ischemia, and in early clinical trials, the therapeutic administration
      of EPCs to patients with myocardial infarction or chronic angina has been
      associated with positive trends in perfusion. EPCs also contribute to endothelial
      repair and may, consequently, impede the development or progression of
      arteriosclerosis. This review provides a brief summary of the preclinical and
      clinical evidence for the role of EPCs in blood-vessel formation and repair
      during ischemic cardiovascular disease.

PMID- 20144625
TI  - Correlation of infrared thermography and skin perfusion in Raynaud patients and
      in healthy controls.
AB  - BACKGROUND: We aimed to investigate the correlation of infrared thermography (IT)
      with laser Doppler perfusion imager (LDPI) among patients with primary Raynaud's
      phenomenon and healthy controls. METHODS: Forty-seven individuals were included:
      we examined 25 patients with primary Raynaud's phenomenon and 22 age and gender
      matched healthy controls. IT of the volar surface of the subjects' left hands was
      performed to record skin temperature while skin perfusion of the same area was
      determined using LDPI. All measurements were obtained at room temperature
      (baseline measurements) and following standardized cold provocation. RESULTS:
      Good correlation of baseline measurements was found between IT and LDPI in
      primary Raynaud patients and healthy controls (r=0.868, p<0.0001 vs. r=0.790,
      p<0.0001). Following cold challenge, correlation was weaker in both groups
      (r=0.742 vs. r=0.766, p<0.0001). Correlation after cold provocation was
      statistically significant among patients with primary Raynaud's phenomenon in
      contrast to controls (Chi Quadrat, p=0.023 vs. p=0.306). CONCLUSION: A
      significant correlation was found between IT and LDPI in primary Raynaud patients
      and in healthy controls (r=0.868 and r=0.742, both p<0.0001). Following cold
      provocation, correlation decreases in both groups. Thus, at room temperature IT
      might substitute for skin perfusion measured by LDPI.

PMID- 20144627
TI  - Differential activity of pro-angiogenic CXC chemokines.
AB  - We showed previously in a mouse model of lung ischemia-induced angiogenesis,
      enhanced expression of the three ELR+ CXC chemokines (KC, LIX, and MIP-2) and
      that blockade of the ligand receptor CXCR(2) limited neovascularization. The
      present study was undertaken to determine the relative abundance and angiogenic
      potential of the three CXC chemokines and whether RhoA activation explained the
      measured differences in potencies. We found that LIX showed the greatest absolute
      amount in the in vivo model 4 h after left pulmonary artery obstruction
      (LIX>KC>MIP-2; p<0.05). In vitro, LIX induced the greatest degree of arterial
      endothelial cell chemotaxis and KC was without effect. A significant increase
      (approximately 40%) in active RhoA was observed with both LIX and MIP-2 compared
      with vehicle control (p<0.05). On average, LIX induced the greatest amount of
      tube formation within pleural tissue in culture. Thus, the results of the present
      study suggest that among the three ELR+ CXC chemokines, LIX predominates in
      eliciting a pro-angiogenic phenotype.

PMID- 20144626
TI  - Endothelial cell activation in a VEGF-A gradient: relevance to cell fate
      decisions.
AB  - Distribution of vascular endothelial cell growth factor A (VEGF-A) as a gradient
      determines microvascular endothelial cell (EC) fate during organogenesis. While
      much is understood about mechanisms of differential distribution, less is known
      about how EC perceive and interpret a graded VEGF-A signal to generate positional
      target gene activation. Using microvascular EC, we analyzed the effect of time
      and graded VEGF-A input on VEGFR2 autophosphorylation, signal kinase activation
      and induction of immediate-early genes. The threshold and time to peak activation
      of VEGFR2 were dependent on signal strength over a 50-fold range in concentration
      with 3-fold concentration differences readily distinguished. Longer duration of
      exposure did not compensate for low concentration of VEGF-A, suggesting intensity
      and duration of signal were not interpreted equivalently. With the same
      conditions, graded and time-sensitive information was transduced through the
      PLCgamma/p44/p42MAPK signal pathway but not the parallel AKT pathway. Analysis of
      MAPK-induced angiogenic immediate-early genes determined that EGR-1, EGR-3, and
      NR4A1 were dependent on graded input while NR4A2 and DSCR1 were independent with
      'switch-like' induction. These data demonstrate rapid, linear integration of VEGF
      A levels but independent interpretation of duration of signal and identify
      potential nodes for segregation of gradient-dependent and -independent responses.
      These results describe how microvascular EC fate decisions can be determined by
      comparatively moderate changes in VEGF signal strength, resulting in
      combinatorial changes in the repertoire of immediate-early genes for
      transcription effectors.

PMID- 20144628
TI  - Dietary factors in chronic inflammation: food tolerances and intolerances of a
      New Zealand Caucasian Crohn's disease population.
AB  - Diet is known to play a major role in the symptoms of the inflammatory bowel
      disease, Crohn's disease (CD). Although no single diet is appropriate to all
      individuals, most CD patients are aware of foods that provide adverse or
      beneficial effects. This study seeks to categorise foods in relation to their
      effects on symptoms of CD, in a New Zealand Caucasian population. Four hundred
      and forty-six subjects from two different centres in New Zealand were recruited
      into the study. An extensive dietary questionnaire (257 food items in 15 groups)
      recorded self-reported dietary tolerances and intolerances. Across each of the
      food groups, there were statistically significant differences among responses to
      foods. A two-dimensional graphical summary enabled stratification of foods
      according to the probability that they will be either beneficial or detrimental.
      A small number of foods are frequently considered to be beneficial, including
      white fish, salmon and tuna, gluten-free products, oatmeal, bananas, boiled
      potatoes, sweet potatoes (kumara), pumpkin, soya milk, goat's milk and yoghurt.
      Foods that are typically considered detrimental include grapefruit, chilli or
      chilli sauce, corn and corn products, peanuts, cream, salami, curried foods, cola
      drinks, high energy drinks, beer, and red wine. For a number of the food items,
      the same item that was beneficial for one group of subjects was detrimental to
      others; in particular soya milk, goat's milk, yoghurt, oatmeal, kiwifruit,
      prunes, apple, broccoli, cauliflower, linseed, pumpkin seed, sunflower seed,
      ginger and ginger products, beef, lamb, liver, and oily fish. It was not possible
      to identify a specific group of food items that should be avoided by all CD
      patients. The wide range of detrimental items suggests that dietary maintenance
      of remission is likely to be difficult, and to exclude a substantial number of
      foods. Personalised diets may be especially important to these individuals.

PMID- 20144629
TI  - Homologous posttranscriptional regulation of insulin-like growth factor-I
      receptor level via glycogen synthase kinase-3beta and mammalian target of
      rapamycin in adrenal chromaffin cells: effect on tau phosphorylation.
AB  - In cultured bovine adrenal chromaffin cells, approximately 24 h-treatment with
      insulin-like growth factor-I (IGF-I) decreased cell surface (125)I-IGF-I binding
      capacity and IGF-I receptor protein level by approximately 64% (EC(50) = 5.0 nM;
      t(1/2) = approximately 7 h). IGF-I-induced IGF-I receptor decrease was abolished
      by LY294002 (phosphoinositide 3-kinase inhibitor) and partially attenuated by
      rapamycin (an inhibitor of mammalian target of rapamycin [mTOR]). SB216763 (an
      inhibitor of glycogen synthase kinase-3 [GSK-3]) down-regulated IGF-I receptor,
      which was further decreased by IGF-I. IGF-I increased inhibitory Ser(9)
      phosphorylation of GSK-3beta and stimulatory Ser(2448)-phosphorylation of mTOR. l
      leucine increased phosphorylation of mTOR (but not GSK-3beta), and down-regulated
      IGF-I receptor, both events being abolished by rapamycin. IGF-I-induced IGF-I
      receptor decrease was not prevented by proteolysis inhibitors. Pulse-label with
      [(35)S]methionine/cysteine followed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis revealed that SB216763 or L-leucine retarded synthesis of IGF-I
      receptor and its precursor molecule. SB216763 (but not l-leucine) destabilized
      IGF-I receptor mRNA and decreased its level, without changing IGF-I receptor gene
      transcription. In SB216763-treated cells, IGF-I-induced Tyr-autophosphorylation
      of IGF-I receptor was decreased by 36%, compared to nontreated cells. IGF-I
      attenuated constitutive Ser(396)-phosphorylation of tau by 30% in nontreated
      cells, but not in SB216763-treated cells. IGF-I-induced down-regulations of
      (125)I-IGF-I binding and IGF-I receptor, as well as IGF-I-induced
      phosphorylations of GSK-3beta and mTOR were restored to the control levels of
      nontreated cells after washout of IGF-I (10 nM for 12 h)-treated cells. Thus, IGF
      I down-regulated functional IGF-I receptor via GSK-3beta inhibition and mTOR
      activation; constitutive activity of GSK-3beta maintained IGF-I receptor level in
      nonstimulated cells.

PMID- 20144630
TI  - Naming manipulable objects: anatomy of a category specific effect in left
      temporal tumours.
AB  - Whether semantic knowledge is categorically organized or is based in an
      undifferentiated distributed network within the temporal lobes or it is at least
      partially organized in property-based networks is still an open issue. With a
      naming task involving living and nonliving entities, the latter divided according
      to degree of manipulability, we studied a group of 30 tumour patients with either
      right, left anterior or left posterior temporal lobes' lesions and a herpes
      simplex encephalitis patient (MU). Both cross-subject and cross-stimulus analyses
      were conducted. Left hemisphere patients were overall worse than both right
      hemisphere patients and controls in the naming task. They moreover named
      nonliving items worse than living. This effect was larger in left posterior
      temporal than both right temporal and also left anterior temporal patients and
      significant both at a cross-subject and cross-stimulus levels of analysis. In
      addition the left posterior temporal group had more difficulties with highly
      manipulable objects than left anterior temporal patients, but the effect was
      significant only on a cross-subject analysis. VLSM lesion analysis revealed that
      the area most critically associated with the larger naming deficit for
      manipulable objects was the posterior superior portion of the left temporal lobe,
      particularly the posterior middle temporal gyrus. These results support a
      'property-based networks' account of semantic knowledge rather than an
      'undifferentiated network' account. For manipulable objects, this would be a
      posterior-temporal/inferior-parietal left hemisphere "action/manipulation
      property-based" network related to the dorsal pathways which is thought to be
      important in action control, as suggested by neuroimaging results.

PMID- 20144631
TI  - Pharmacological evidence that both cognitive memory and habit formation
      contribute to within-session learning of concurrent visual discriminations.
AB  - The monkey's ability to learn a set of visual discriminations presented
      concurrently just once a day on successive days (24-h ITI task) is based on habit
      formation, which is known to rely on a visuo-striatal circuit and to be
      independent of visuo-rhinal circuits that support one-trial memory. Consistent
      with this dissociation, we recently reported that performance on the 24-h ITI
      task is impaired by a striatal-function blocking agent, the dopaminergic
      antagonist haloperidol, and not by a rhinal-function blocking agent, the
      muscarinic cholinergic antagonist scopolamine. In the present study, monkeys were
      trained on a short-ITI form of concurrent visual discrimination learning, one in
      which a set of stimulus pairs is repeated not only across daily sessions but also
      several times within each session (in this case, at about 4-min ITIs). Asymptotic
      discrimination learning rates in the non-drug condition were reduced by half,
      from approximately 11 trials/pair on the 24-h ITI task to approximately 5
      trials/pair on the 4-min ITI task, and this faster learning was impaired by
      systemic injections of either haloperidol or scopolamine. The results suggest
      that in the version of concurrent discrimination learning used here, the short
      ITIs within a session recruit both visuo-rhinal and visuo-striatal circuits, and
      that the final performance level is driven by both cognitive memory and habit
      formation working in concert.

PMID- 20144632
TI  - Developmental topographical disorientation in a healthy subject.
AB  - We present the case of F.G., a healthy, normally developed 22-year-old male
      subject affected by a pervasive disorder in environmental orientation and
      navigation who presents no history of neurological or psychiatric disease. A
      neuro-radiological examination showed no evidence of anatomical or structural
      alterations to the brain. We submitted the subject for a comprehensive
      neuropsychological assessment of the different cognitive processes involved in
      topographical orientation to evaluate his ability to navigate the spatial
      environment. The results confirmed a severe developmental topographical disorder
      and deficits in a number of specific cognitive processes directly or indirectly
      involved in navigation. The results are discussed with reference to the sole
      previously described case of developmental topographical disorientation (Pt1;
      Iaria et al., 2009). F.G. differs from the former case due to the following: the
      greater severity of his disorder, his complete lack of navigational skills, the
      failure to develop compensatory strategies, and the presence of a specific
      deficit in processing the spatial relationships between the parts of a whole. The
      present case not only confirms the existence of developmental topographical-skill
      disorders, but also sheds light on the architecture of topographical processes
      and their development in human beings.

PMID- 20144633
TI  - Distribution and metabolism of four different dimethylated arsenicals in
      hamsters.
AB  - Arsenic toxicity and distribution are highly dependent on animal species and its
      chemical species. Recently, thioarsenical has been recognized in highly toxic
      arsenic metabolites, which was commonly found in human and animal urine. In the
      present study, we revealed the mechanism underlying the distribution and
      metabolism of non-thiolated and thiolated dimethylarsenic compounds such as
      dimethylarsinic acid (DMA(V)), dimethylarsinous acid (DMA(III)),
      dimethylmonothioarsinic acid (DMMTA(V)), and dimethyldithioarsinic acid
      (DMDTA(V)) after the administration of them into femoral vein of hamsters. DMA(V)
      and DMDTA(V) distributed in organs and body fluids were in their unmodified form,
      while DMA(III) and DMMTA(V) were bound to proteins and transformed to DMA(V) in
      organs. On the other hand, DMA(V) and DMDTA(V) were mostly excreted into urine as
      their intact form 1 h after post-injection, and more than 70% of the doses were
      recovered in urine as their intact form. By contrast, less than 8-14% of doses
      were recovered in urine as DMA(V), while more than 60% of doses were distributed
      in muscles and target organs (liver, kidney, and lung) of hamsters after the
      injection of DMMTA(V) and DMA(III). However, in red blood cells (RBCs), only a
      small amount of the arsenicals was distributed (less than 4% of the doses) after
      the injection of DMA(III) and DMMTA(V), suggesting that the DMA(III) and DMMTA(V)
      were hardly accumulated in hamster RBCs. Based on these observations, we suggest
      that although DMMTA(V) and DMDTA(V) are thioarsenicals, DMMTA(V) is taken up
      efficiently by organs, in a manner different from that of DMDTA(V). In addition,
      the distribution and metabolism of DMMTA(V) are like in manner similar to
      DMA(III) in hamsters, while DMDTA(V) is in a manner similar to DMA(V).

PMID- 20144634
TI  - Silymarin modulates doxorubicin-induced oxidative stress, Bcl-xL and p53
      expression while preventing apoptotic and necrotic cell death in the liver.
AB  - The emergence of silymarin (SMN) as a natural remedy for liver diseases, coupled
      with its entry into NIH clinical trial, signifies its hepatoprotective potential.
      SMN is noted for its ability to interfere with apoptotic signaling while acting
      as an antioxidant. This in vivo study was designed to explore the hepatotoxic
      potential of Doxorubicin (Dox), the well-known cardiotoxin, and in particular
      whether pre-exposures to SMN can prevent hepatotoxicity by reducing Dox-induced
      free radical mediated oxidative stress, by modulating expression of apoptotic
      signaling proteins like Bcl-xL, and by minimizing liver cell death occurring by
      apoptosis or necrosis. Groups of male ICR mice included Control, Dox alone, SMN
      alone, and Dox with SMN pre/co-treatment. Control and Dox groups received saline
      i.p. for 14 days. SMN was administered p.o. for 14 days at 16 mg/kg/day. An
      approximate LD(50) dose of Dox, 60 mg/kg, was administered i.p. on day 12 to
      animals receiving saline or SMN. Animals were euthanized 48 h later. Dox alone
      induced frank liver injury (>50-fold increase in serum ALT) and oxidative stress
      (>20-fold increase in malondialdehyde [MDA]), as well as direct damage to DNA
      (>15-fold increase in DNA fragmentation). Coincident genomic damage and oxidative
      stress influenced genomic stability, reflected in increased PARP activity and p53
      expression. Decreases in Bcl-xL protein coupled with enhanced accumulation of
      cytochrome c in the cytosol accompanied elevated indexes of apoptotic and
      necrotic cell death. Significantly, SMN exposure reduced Dox hepatotoxicity and
      associated apoptotic and necrotic cell death. The effects of SMN on Dox were
      broad, including the ability to modulate changes in both Bcl-xL and p53
      expression. In animals treated with SMN, tissue Bcl-xL expression exceeded
      control values after Dox treatment. Taken together, these results demonstrated
      that SMN (i) reduced, delayed onset, or prevented toxic effects of Dox which are
      typically associated with hydroxyl radical production, (ii) performed as an
      antioxidant limiting oxidative stress, (iii) protected the integrity of the
      genome, and (iv) antagonized apoptotic and necrotic cell death while increasing
      antiapoptotic Bcl-xL protein levels and minimizing the leakage of proapoptotic
      cytochrome c from liver mitochondria. These observations demonstrate the
      protective actions of SMN in liver, and raise the possibility that such
      protection may extend to other organs during Dox treatment including the heart.

PMID- 20144635
TI  - Blood cell oxidative stress precedes hemolysis in whole blood-liver slice co
      cultures of rat, dog, and human tissues.
AB  - A novel in vitro model to investigate time-dependent and concentration-dependent
      responses in blood cells and hemolytic events is studied for rat, dog, and human
      tissues. Whole blood is co-cultured with a precision-cut liver slice. Methimazole
      (MMI) was selected as a reference compound, since metabolism of its imidazole
      thione moiety is linked with hematologic disorders and hepatotoxicity. An
      oxidative stress response occurred in all three species, marked by a decline in
      blood GSH levels by 24 h that progressed, and preceded hemolysis, which occurred
      at high MMI concentrations in the presence of a liver slice with rat (>or=1000
      microM at 48 h) and human tissues (>or=1000 microM at 48 h, >or=750 microM at 72
      h) but not dog. Human blood-only cultures exhibited a decline of GSH levels but
      minimal to no hemolysis. The up-regulation of liver genes for heme degradation
      (Hmox1 and Prdx1), iron cellular transport (Slc40a1), and GSH synthesis and
      utilization (mGST1 and Gclc) were early markers of the oxidative stress response.
      The up-regulation of the Kupffer cell lectin Lgals3 gene expression indicated a
      response to damaged red blood cells, and Hp (haptoglobin) up-regulation is
      indicative of increased hemoglobin uptake. Up-regulation of liver IL-6 and IL-8
      gene expression suggested an activation of an inflammatory response by liver
      endothelial cells. In summary, MMI exposure led to an oxidative stress response
      in blood cells, and an up-regulation of liver genes involved with oxidative
      stress and heme homeostasis, which was clearly separate and preceded frank
      hemolysis.

PMID- 20144636
TI  - A physiologically based biodynamic (PBBD) model for estragole DNA binding in rat
      liver based on in vitro kinetic data and estragole DNA adduct formation in
      primary hepatocytes.
AB  - Estragole has been shown to be hepatocarcinogenic in rodent species at high-dose
      levels. Translation of these results into the likelihood of formation of DNA
      adducts, mutation, and ultimately cancer upon more realistic low-dose exposures
      remains a challenge. Recently we have developed physiologically based biokinetic
      (PBBK) models for rat and human predicting bioactivation of estragole. These PBBK
      models, however, predict only kinetic characteristics. The present study
      describes the extension of the PBBK model to a so-called physiologically based
      biodynamic (PBBD) model predicting in vivo DNA adduct formation of estragole in
      rat liver. This PBBD model was developed using in vitro data on DNA adduct
      formation in rat primary hepatocytes exposed to 1'-hydroxyestragole. The model
      was extended by linking the area under the curve for 1'-hydroxyestragole
      formation predicted by the PBBK model to the area under the curve for 1'
      hydroxyestragole in the in vitro experiments. The outcome of the PBBD model
      revealed a linear increase in DNA adduct formation with increasing estragole
      doses up to 100 mg/kg bw. Although DNA adduct formation of genotoxic carcinogens
      is generally seen as a biomarker of exposure rather than a biomarker of response,
      the PBBD model now developed is one step closer to the ultimate toxic effect of
      estragole than the PBBK model described previously. Comparison of the PBBD model
      outcome to available data showed that the model adequately predicts the dose
      dependent level of DNA adduct formation. The PBBD model predicts DNA adduct
      formation at low levels of exposure up to a dose level showing to cause cancer in
      rodent bioassays, providing a proof of principle for modeling a toxicodynamic in
      vivo endpoint on the basis of solely in vitro experimental data.

PMID- 20144637
TI  - Histopathological effects of [D-Leu(1)]Microcystin-LR variants on liver, skeletal
      muscle and intestinal tract of Hypophthalmichthys molitrix (Valenciennes, 1844).
AB  - This study evaluated the effects of [D-Leu(1)]Microcystin-LR variants, by the
      exposure of Hypophthalmichthys molitrix to Microcystis aeruginosa NPLJ4. Fish was
      placed in aquariums and exposed to 10(5) cells mL(-1). For 15 days, 05
      individuals were removed every 05 days, and tissue samples of liver, skeletal
      muscle and intestinal tract were collected for histopathologic analyses.
      Following exposure, those surviving were placed in clean water for 15 days to
      evaluate their recovery. A control without toxins was maintained in the same
      conditions and exhibited normal histology and no tissue damage. In exposed fish,
      samples were characterized by serious damages that similarly affected the
      different organs, such as dissociation of cells, necrosis and haemorrhage.
      Samples showed signs of recovery but severe damages were still observed. The
      results should be valuable to analyze the potency of microcystin toxicity and to
      help in the diagnosis of fish deaths.

PMID- 20144638
TI  - Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja
      nigricollis CMS-9-induced apoptosis of human leukemia K562 cells.
AB  - CMS-9, a phospholipase A(2) (PLA(2)) isolated from Naja nigricollis venom,
      induced apoptosis of human leukemia K562 cells, characterized by mitochondrial
      depolarization, modulation of Bcl-2 family members, cytochrome c release and
      activation of caspases 9 and 3. Moreover, an increase in intracellular Ca2+
      concentration and the production of reactive oxygen species (ROS) was noted.
      Pretreatment with BAPTA-AM (Ca2+ chelator) and N-acetylcysteine (NAC, ROS
      scavenger) proved that Ca2+ was an upstream event in inducing ROS generation.
      Upon exposure to CMS-9, activation of p38 MAPK and JNK was observed in K562
      cells. BAPTA-AM or NAC abrogated CMS-9-elicited p38 MAPK and JNK activation, and
      rescued viability of CMS-9-treated K562 cells. SB202190 (p38 MAPK inhibitor) and
      SP600125 (JNK inhibitor) suppressed CMS-9-induced dissipation of mitochondrial
      membrane potential, Bcl-2 down-regulation, Bax up-regulation and increased
      mitochondrial translocation of Bax. Inactivation of PLA(2) activity reduced
      drastically the cytotoxicity of CMS-9, and a combination of
      lysophosphatidylcholine and stearic acid mimicked the cytotoxic effects of CMS-9.
      Taken together, our data suggest that CMS-9-induced apoptosis of K562 cells is
      catalytic activity-dependent and is mediated through mitochondria-mediated death
      pathway triggered by Ca2+/ROS-evoked p38 MAPK and JNK activation.

PMID- 20144639
TI  - Morphological cell transformation of Syrian hamster embryo (SHE) cells by the
      cyanotoxin, cylindrospermopsin.
AB  - Cylindrospermopsin (CYN) is a cyanotoxin which has been implicated in human
      intoxication and animal mortality. Genotoxic activity of this hepatotoxin is
      known but its carcinogenic activity remains to be elucidated. In this work, CYN
      was assessed for its cell-transforming activity using the Syrian hamster embryo
      (SHE) cell transformation assay. This in vitro assay is used to evaluate the
      carcinogenic potential of chemical, physical and biological agents in SHE cells,
      which are primary, normal, diploid, genetically stable and capable of metabolic
      activation. We demonstrated that CYN induced a significant increase in
      morphological cell transformation in SHE cells following a 7-day continuous
      treatment in the range of non-cytotoxic concentrations 1 x 10(-7)-1 x 10(-2)
      ng/mL.

PMID- 20144640
TI  - Helicobacter pylori virulence factors as tools to study human migrations.
AB  - Helicobacter pylori is one of the most common infections worldwide. In most
      individuals it consists in a lifelong host-pathogen relationship without
      consequences, but in some subjects it is associated with peptic ulcer disease and
      gastric cancer. Polymorphism in genes that code bacterial virulence factors, cagA
      and vacA, are independently associated with the infection severe outcomes and are
      geographically diverse. In the last decade, accumulated knowledge allowed to
      characterize typical H. pylori strain patterns for all the major human
      populations; patterns that can be used to study the origin of specific human
      groups. Thus, the presence or absence of cagA, cagA EPIYA genotypes, and vacA
      subtypes can be used as tools to study not only the geographic origin of specific
      human populations, but also to identify markers of historical contact between
      different ethnicities. We report here a study including a set of native Amazon
      Amerindians that had supposedly been some, but little, contact with European
      Brazilian colonizer and/or African slaves. They harbor H. pylori strains in a
      mixed pattern with Asian and Iberian Peninsula characteristics. It is possible
      that this finding represents H. pylori recombination upon short contact between
      human groups. Alternatively, it could be due to a founder effect from a small
      cluster of Asian origin native Americans.

PMID- 20144641
TI  - Loxoscelism: From basic research to the proposal of new therapies.
AB  - Loxoscelism is caused by envenomation by spiders from Loxosceles genus. Clinical
      symptoms only appear a few hours after envenomation and can evolve in local
      reactions, such as dermonecrosis, and systemic reactions, such as intravascular
      haemolysis, intravascular coagulation and renal failure. Current therapies are
      not effective, often not based in scientific research and can be even
      detrimental. A lack of understanding of the mechanism of action of the venom of
      the Loxosceles spider had thus far prevented development of effective therapies.
      In this review we aim to give an overview of our contributions to the
      understanding of the mechanism of action of the Loxosceles venom and propose
      targets and therapeutics for medical intervention.

PMID- 20144642
TI  - Down-regulation of the JAK2/PI3K-mediated signaling activation is involved in
      Taiwan cobra cardiotoxin III-induced apoptosis of human breast MDA-MB-231 cancer
      cells.
AB  - Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues
      isolated from Naja naja atra venom, has been reported to have anticancer
      activity. Exposure of MDA-MB-231 cells with 0.03, 0.09, and 0.15 microM of CTX
      III for 18 h, CTX III-induced cell apoptosis, as evidenced by accumulation of sub
      G1 population, externalization of phosphatidylserine, loss of mitochondrial
      membrane potential (DeltaPsim) with subsequent release of cytochrome c, and
      activation of both capases-9 and caspase-3. This correlated with up-regulation in
      Bax and Bad, and down-regulation of various anti-apoptotic proteins, including
      Bcl-2, Bcl-X(L), and survivin in CTX III-treated cells. Mechanistic studies
      showed that CTX III suppressed the phosphorylation of JAK2, STAT3, Akt, and
      activation of PI3K. Moreover, the PI3K inhibitor wortmannin blocked activation of
      STAT3 and Akt without affecting the JAK2 activation, whereas JAK2 inhibitor AG490
      suppressed the levels of phospho-STAT3, phospho-Akt, and PI3K, suggesting that
      PI3K activation occurs after JAK2 phosphorylation, and both PI3K and JAK2 kinases
      cooperate to mediate STAT3 and Akt phosphorylation. Both AG490 and wortmannin
      also led to up-regulation in Bax and Bad, and down-regulation of Bcl-2, Bcl-X(L),
      and survivin in MDA-MB-231 cells. Taken together, these results indicate that CTX
      III induces apoptosis in MDA-MB-231 cells via concomitant inactivation of the
      JAK2, STAT3, PI3K, and Akt signaling pathways.

PMID- 20144643
TI  - Metallothionein-I/II null cardiomyocytes are sensitive to Fusarium mycotoxin
      butenolide-induced cytotoxicity and oxidative DNA damage.
AB  - Previous studies revealed butenolide (BUT), a Fusarium mycotoxin distributes
      extensively, induced myocardial oxidative damage, which could be abated by
      antioxidants such as glutathione. Metallothionein (MT) has proved to attenuate
      several oxidative cardiomyopathies via its potent antioxidant property. The
      present study is therefore undertaken to investigate the protective potential of
      the endogenous expression of MT against BUT-induced myocardial toxicity. Primary
      cultures of neonatal cardiomyocytes from MT-I/II null mice along with the
      corresponding wild-type mice will be utilized to determine the possible
      mechanistic properties of MT. BUT treatment to the cardiomyocytes evoked
      significant cytotoxicity as evidenced by morphological changes and concentration-
      and time-dependent reductions in cell viability. Additionally, BUT treatment
      remarkably increased reactive oxygen species (ROS) production in the
      cardiomyocytes of both MT-I/II null and wild-type mice. As a result, noticeable
      DNA damage in both cardiomyocytes was detected by alkaline comet assay.
      Furthermore, the comparison between the MT-I/II null and wild-type cardiomyocytes
      indicated that ROS production in the cardiomyocytes from the MT-I/II null mice
      was higher than from wild-type mice. DNA damage as evaluated by percentage of
      comet tail DNA, tail length and tail moment was more severe in the MT-l/II null
      cardiomyocytes than in wild-type myocytes. And in agreement with those results
      mentioned above, the MT-l/II null cardiomyocytes were more sensitive to BUT
      induced cytotoxicity than wild-type cardiomyocytes. Taken together, these
      findings clearly show that basal MT can efficiently attenuate BUT-induced
      cytotoxic injuries in cardiomyocytes via the inhibition of intracellular ROS
      production, and associated DNA damage.

PMID- 20144644
TI  - P- and R-type Ca2+ channels regulating spinal glycinergic nerve terminals.
AB  - The contributions of P- and R-type Ca2+ channels on glycinergic nerve endings
      (boutons) projecting to the rat spinal sacral commissural nucleus (SDCN) neurons
      are not understood. Thus, we investigated the functional role of P- and R-type
      Ca2+ channels by measuring the inhibitory postsynaptic currents (eIPSCs) evoked
      from individual nerve endings (boutons) by focal electrical stimulation. The
      current amplitude and failure rate (Rf) of glycinergic eIPSCs varied directly
      with changes in [Ca2+](o). Low concentration of omega-Aga IVA (P-type selective
      antagonist) suppressed eIPSCs as much as high concentration (both P- and Q-type
      selective) indicating little contribution of Q-type Ca2+ channels. Antagonism of
      R-type Ca2+ channels with SNX-482 and Ni2+ greatly decreased the current
      amplitude and increased failure rate (Rf) of glycinergic eIPSCs. Overall, our
      results suggest that the dominant control of glycine release depends on Ca2+
      entry through P- and R-type Ca2+ channels that ubiquitously populate spinal
      glycine release sites.

PMID- 20144645
TI  - Asymmetries in the direction of saccades during perception of scenes and
      fractals: effects of image type and image features.
AB  - The direction in which people tend to move their eyes when inspecting images can
      reveal the different influences on eye guidance in scene perception, and their
      time course. We investigated biases in saccade direction during a memory-encoding
      task with natural scenes and computer-generated fractals. Images were rotated to
      disentangle egocentric and image-based guidance. Saccades in fractals were more
      likely to be horizontal, regardless of orientation. In scenes, the first saccade
      often moved down and subsequent eye movements were predominantly vertical,
      relative to the scene. These biases were modulated by the distribution of visual
      features (saliency and clutter) in the scene. The results suggest that image
      orientation, visual features and the scene frame-of-reference have a rapid effect
      on eye guidance.

PMID- 20144646
TI  - Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson
      disease.
AB  - LRRK2 mutations are recognized as the most frequent genetic cause of both
      familial and sporadic parkinsonism identified to date. A remarkable feature of
      this form of parkinsonism is the variable penetrance of symptom manifestation
      resulting in a wide range of age-at-onset in patients. Herein we use a functional
      approach to identify the Lrrk1 protein as a potential disease modifier
      demonstrating an interaction and heterodimer formation with Lrrk2. In addition,
      evaluation of LRRK1 variants in our large Lrrk2 p.G2019S-parkinsonism series from
      a Tunisian (n=145) identified a missense mutation (p.L416M) resulting in an
      average 6.2 years younger age at disease onset. In conclusion we show that the
      interaction of Lrrk1-Lrrk2 can form protein dimers and this interaction may
      influence the age of symptomatic manifestation in Lrrk2-parkinsonism patients.

PMID- 20144648
TI  - Using geographic information system analyses to monitor large-scale distribution
      of nicotine replacement therapy in New York City.
AB  - OBJECTIVE: Since 2003, the New York City Department of Health and Mental Hygiene
      has distributed nicotine replacement therapy nicotine replacement therapy to
      adult smokers through annual large-scale distribution programs. METHODS: In 2008,
      the New York City Department of Health and Mental Hygiene formally integrated
      geographic information system analyses to track program enrollment, map the
      geographic density of enrollees, and assess the effects of outreach strategies.
      RESULTS: Geographic information system analyses provided a unique, near real-time
      visual method of assessing participation patterns as well as the impact of media
      and outreach strategies. Among neighborhoods with high smoking prevalence, lower
      income neighborhoods had higher enrollment compared to higher income
      neighborhoods. Mapping before and after a press release demonstrated that program
      interest increased over 700% in one area. CONCLUSION: Although geographic
      information system analysis is traditionally utilized for large-scale infectious
      disease surveillance, the New York City Department of Health and Mental Hygiene
      used GIS to inform and improve an annual large-scale smoking cessation program.
      These analyses provide unique feedback that can aid public health program
      planners in improving efficiency and efficacy of service delivery.

PMID- 20144647
TI  - Long-term impact of neonatal injury in male and female rats: Sex differences,
      mechanisms and clinical implications.
AB  - Over the last several decades, the relative contribution of early life events to
      individual disease susceptibility has been explored extensively. Only fairly
      recently, however, has it become evident that abnormal or excessive nociceptive
      activity experienced during the perinatal period may permanently alter the normal
      development of the CNS and influence future responses to somatosensory input.
      Given the significant rise in the number of premature infants receiving high
      technology intensive care over the last 20 years, ex-preterm neonates may be
      exceedingly vulnerable to the long-term effects of repeated invasive
      interventions. The present review summarizes available clinical and laboratory
      findings on the lasting impact of exposure to noxious stimulation during early
      development, with a focus on the structural and functional alterations in
      nociceptive circuits, and its sexually dimorphic impact.

PMID- 20144649
TI  - A procedure for characterizing glucans synthesized by purified enzymes of
      cariogenic Streptococcus mutans.
AB  - Extracellular polysaccharide is a virulence factor of the most cariogenic
      bacteria, Streptococcus mutans. We describe a procedure for chemical analysis of
      this polysaccharide of S. mutans, using a well-known glucan synthesized by
      purified enzymes of cariogenic streptococci. Soluble and insoluble glucan from
      glucosyltransferase D and B respectively, were prepared and analyzed by nuclear
      magnetic resonance spectroscopy and methylation. Soluble alpha-glucan contained
      60% of (1-->6)-linkages and 17% of branching while insoluble alpha-glucan was
      composed of 57% of (1-->3)- and 28% of (1-->6)-linkages with 8% branching. The
      described procedure could be important focusing future studies on in vivo
      biofilm.

PMID- 20144650
TI  - Infection with the trypanosome Crithidia bombi and expression of immune-related
      genes in the bumblebee Bombus terrestris.
AB  - Social bees and other insects are frequently parasitized by a large range of
      different microorganisms. Among these is Crithidia bombi (Kinetoplastida:
      Trypanosomatidae), a common gut parasite of bumblebees, Bombus spp. (Insecta:
      Apidae). Bumblebees are important pollinators in commercial and natural
      environments. There are clear detrimental effects of C. bombi infections on the
      fitness of bumblebees. However, little has been known about how the bee's immune
      system responds to infections with trypanosome parasites. Here, we study the
      immune response of Bombus terrestris on infection by C. bombi. We measured the
      expression of four immune-related genes (Hemomucin, MyD88, Relish, and TEP7)
      using RT-qPCR in adult B. terrestris workers that were either healthy or infected
      with the trypanosome parasite C. bombi. The potential recognition gene Hemomucin
      was significantly upregulated in the infected bees. Further, there was
      substantial and significant variation in all four genes among different bumblebee
      colonies irrespective of infection status.

PMID- 20144651
TI  - Mapping of the nick site on conjugative plasmid pVT745 by interrupted mating.
AB  - Conjugal transfer of plasmid DNA initiates and terminates at a specific non
      coding site called the origin of transfer (oriT). Previous analysis of
      conjugative plasmid pVT745 from Aggregatibacter actinomycetemcomitans suggested
      that oriT was located adjacent to the operon responsible for initiation of ssDNA
      transfer. The location of oriT was confirmed by assaying both subclones of the
      region as well as a pVT745 deletion derivative for mobilization. The precise DNA
      nick site (nic) and polarity of DNA transfer were identified by use of
      interrupted mating assays, a technique originally used for the mapping of
      bacterial chromosomes. Nucleotide sequence analysis revealed that the pVT745
      specific nick region was similar to the consensus nick sequence of the IncP
      family albeit the actual cleavage site differed. Functionality of nic was
      confirmed by point mutations.

PMID- 20144652
TI  - RTN/Nogo in forming Alzheimer's neuritic plaques.
AB  - One of the pathological hallmarks in brains of patients with Alzheimer's disease
      (AD) is the presence of neuritic plaques, in which amyloid deposits are
      surrounded by reactive gliosis and dystrophic neurites. Within neuritic plaques,
      reticulon 3 (RTN3), a homolog of Nogo protein, appears to regulate the formation
      of both amyloid deposition via negative modulation of BACE1 activity and
      dystrophic neurites via the formation of RTN3 aggregates. Transgenic mice over
      expressing RTN3, but not the other known markers of dystrophic neurites in AD
      brain, spontaneously develop RTN3-immunoreactive dystrophic neurites. The
      presence of dystrophic neurites impairs cognition. Blocking abnormal RTN3
      aggregation will increase the available RTN3 monomer and is therefore a promising
      therapeutic strategy for enhancing cognitive function in AD patients.

PMID- 20144653
TI  - Neuroimaging predictors of transition to psychosis--a systematic review and meta
      analysis.
AB  - OBJECTIVES: In early stage psychosis research the identification of
      neurobiological correlates of vulnerability to schizophrenia is an important
      hurdle. METHODS: We systematically reviewed the neuroimaging publications on high
      risk subjects with subsequent transition to psychosis (HR-T) and conducted a meta
      analysis calculating the effect size Cohen's d. RESULTS: Out of 30 identified
      studies 25 met the inclusion criteria. Structural (s)MRI studies showed small to
      medium effect sizes of decreased prefrontal, cingulate, insular and cerebellar
      gray matter volume in HR-T compared to high-risk subjects without transition (HR
      NT). Meta-analysis revealed relatively larger whole brain volumes in HR-T
      compared to HR-NT subjects (mean Cohen's d 0.36, 95% CI 0.27-0. 46). Compared to
      HR-NT, HR-T subjects showed in functional imaging studies reduced brain
      activation in prefrontal cortex, reduced neuronal density, and increased membrane
      turnover in frontal and cingulate cortex with medium to large effect sizes.
      CONCLUSIONS: Despite methodological differences between studies, structural and
      neurochemical abnormalities in prefrontal, anterior cingulate, medial temporal
      and cerebellar cortex might be predictive for development of psychosis within HR
      subjects.

PMID- 20144654
TI  - In silico evidence for glutathione- and iron-related pathogeneses in Parkinson's
      disease.
AB  - Post-mortem analyses and epidemiological studies strongly indicate metals have a
      participatory role in neurodegenerative diseases, but whether these roles are
      pathogenic and not simply subsidiary mechanisms is currently unclear. For
      Parkinson's disease (PD), iron content in the afflicted brain region, the
      substantia nigra pars compacta (SNpc), has been consistently reported elevated
      whereas copper levels have been decreased. Both metals exhibit deleterious
      functions that occur during the late stages of PD, but mutations involving the
      regulation of these two metals have not been associated with PD. The pathogenesis
      of PD is undoubtedly multifaceted and may consist of various etiological factors
      participating in slow disease ascension. However, the extent to which certain
      factors may contribute to PD is unclear. To study whether iron and/or copper may
      facilitate a parkinsonian state, a computational model of neuronal metal
      regulation was initially developed and then the system was perturbed,
      corresponding to proposed etiological pathways for PD from the literature, in
      order to determine which iron- and copper-based pathogeneses would elicit a
      parkinsonian system. We report that a defective glutathione system and/or
      inhibited cellular iron efflux have the neurotoxic capacities to initiate a
      system characteristic of PD; furthermore, these capacities are greatly enhanced
      with mutated alpha-synuclein proteins.

PMID- 20144655
TI  - Diabetes acceleration by cyclophosphamide in the non-obese diabetic mouse is
      associated with differentiation of immunosuppressive monocytes into
      immunostimulatory cells.
AB  - Cyclophosphamide (CTX) was previously shown to induce the recruitment of
      immunosuppressive myeloid cells in mouse. In the non-obese diabetic (NOD) mouse,
      which develops spontaneously type I diabetes, CTX is widely known to accelerate
      the autoimmune process. Our data demonstrated that CTX actually did mobilize an
      immunosuppressive myeloid CD11b(+) Ly-6G(-) population in the NOD mouse spleen in
      addition to a well-identified neutrophil CD11b(+) Ly-6G(+) population. CD11b(+)
      Ly-6G(-) cells, in contrast with CD11b(+) Ly-6G(+) cells, were able to inhibit in
      vitro mitogen-induced syngeneic T cell proliferation. CD11b(+) Ly-6G(-) cells
      represented a heterogeneous population mainly made of CD31(hi) cells and Ly-6C(+)
      monocytes. Only these last ones supported the immunosuppressive in vitro activity
      and resembled circulating inflammatory monocytes according to flow cytometry,
      cytology and RT-PCR data. Although CD11b(+) Ly-6G(-) Ly-6C(+) cells exhibited
      immunosuppressive function in vitro, they were not able to control the autoimmune
      response following CTX injection. Our data show that these CTX-induced
      immunosuppressive myeloid cells actually behaved as very plastic cells in vitro.
      Likewise, in the model of prediabetic NOD/SCID mice, CD11b(+) Ly-6G(-) Ly-6C(+)
      were able to differentiate into CD11c+ cells after i.v. injection. Herein, we
      described a new mechanism by which CTX might induce diabetes acceleration in the
      NOD mouse. In summary, recruited immunosuppressive cells might participate in the
      immunopotentiating effect of CTX on the autoimmune response by their further
      differentiation into immunostimulatory cells.

PMID- 20144656
TI  - A rapid test for the detection of influenza A virus including pandemic influenza
      A/H1N1 2009.
AB  - A new rapid diagnostic test for detection of influenza A virus was evaluated with
      four sets of experiments: first, a comparison with a commercial diagnostic kit
      against a panel of virus strains was conducted; second, the kit was tested
      against a collection of 40 strains of influenza A virus isolated from five
      different host species and 26 strains of other respiratory viruses used as
      controls; third, the kit was tested against specimens collected in the field
      obtained from human and chicken; and fourth, the kit was tested against the novel
      pandemic influenza A/H1N1 2009 clinical specimens obtained from admitted to
      hospital patients. The test kit displayed a sensitivity of 88% for both human
      specimens and avian specimens. The corresponding specificity was 99.3% for human
      specimens and 96.5% for avian specimens. This test kit may be useful for rapid
      diagnosis of influenza A virus.

PMID- 20144657
TI  - Functional cooperation between the hippocampal subregions and the medial septum
      in unreinforced and reinforced spatial memory tasks.
AB  - Anatomical connections between the medial septum (MS) and hippocampus (Hipp) via
      the fimbria-fornix suggest that functional cooperation between these structures
      may be important for the acquisition and use of spatial reference memories. The
      present study examined the extent to which this was true for both an unreinforced
      learning task (object exploration task) and a reinforced learning task (Morris
      water maze task). In Experiment 1, we compared the performance of MS/Hipp
      contralateral- and MS/Hipp ipsilateral-lesioned rats. MS/Hipp contralateral
      lesioned rats exhibited deficient performance in both the object exploration and
      Morris water maze tasks. In Experiment 2, we examined the task performance of
      MS/CA1 contralateral-, MS/CA1 ipsilateral-, MS/CA3 contralateral- and MS/CA3
      ipsilateral-lesioned rats. Contralateral MS/CA3 and MS/CA1 lesions were
      respectively associated with deficient performance at the spatial recognition
      test and object recognition test in the object exploration task. None of the
      lesioned rats performed deficiently in the Morris water maze task. These results
      indicate the importance of spatial reference memory of a functional cooperation
      between the MS and Hipp as a whole, irrespective of reward contingency. In
      contrast, functional cooperation between the MS and each of CA1 and CA3 played an
      important role in the performance of the unreinforced voluntary task, but not in
      the reinforced task. Further, the functional cooperation of both MS/CA3 and
      MA/CA1 were important in the spatial reference memory with the unreinforced task.

PMID- 20144658
TI  - Role of serotonergic 5-HT1A and oxytocinergic receptors of the lateral septal
      area in sodium intake regulation.
AB  - Several reports have revealed a high density of 5-HT(1A) receptors in the lateral
      septal area (LSA), as well as a subpopulation of oxytocin (OT) receptors.
      Increasing evidence shows that 5-HT(1A) and OT neurons inhibit sodium urinary
      excretion. The aim of this study was to investigate the part played by
      serotonergic (5-HT(1A)) and oxytocinergic receptors in the LSA in the sodium
      intake induced in rats by sodium depletion followed by 24h deprivation. Cannulae
      were implanted bilaterally into the LSA of rats to enable the introduction of
      receptor ligands into that brain area. Serotonergic injections of 5-HT (10, 20,
      and 40 microg/0.2 microL) reduced 1.8% NaCl solution intake, but injections (1,
      2, and 4 microg/0.2 microL) of 8-OH-DPAT, a 5-HT(1A) agonist, were more effective
      than 5-HT in reducing 1.8% NaCl intake. Pretreatment of the LSA with the 5-HT(1A)
      antagonist pMPPF partially reduced the inhibitory effect of 5-HT and totally
      reversed the effects of 8-OH-DPAT on 1.8% NaCl intake induced by sodium
      depletion. Previous treatment with the potent oxytocin receptor antagonist
      d(CH(2))(5)[Tyr(Me)(2)Thr(4), Orn(5), Tyr(NH(2))(9)]-vasotocin also totally
      blocked the inhibitory effects of 5-HT or 8-OH-DPAT on 1.8% NaCl intake. These
      results show that 5-HT(1A) serotonergic receptors in the LSA, including some that
      interact with the oxytocinergic system, modulate sodium intake induced by sodium
      loss in rats.

PMID- 20144659
TI  - alpha-Tocopherol administration produces an antidepressant-like effect in
      predictive animal models of depression.
AB  - This study investigated the antidepressant potential of alpha-tocopherol, the
      most active and abundant form of vitamin E, in the forced swim test (FST) and
      tail suspension test (TST). The acute oral treatment with alpha-tocopherol at the
      doses of 30 and 100mg/kg reduced the immobility time in the FST and in the TST. A
      single i.c.v. administration of alpha-tocopheryl phosphate, a water-soluble
      analogue of alpha-tocopherol, also reduced the immobility time in the FST (0.1
      and 1 nmol/site) and in the TST (0.1 nmol/site). In addition, the long-term
      treatment (28 days) with alpha-tocopherol (10mg/kg, p.o.) significantly reduced
      the immobility time in the FST. Moreover, a subeffective dose of alpha-T
      (10mg/kg, p.o.) potentiated the effect of fluoxetine (10mg/kg, p.o.) in the FST.
      The long-term treatment with alpha-T was able to increase the glutathione (GSH)
      antioxidant defense system, while the acute treatment was not. The long-term
      treatment with alpha-tocopherol (10mg/kg) increased the GSH levels in the
      hippocampus and in the prefrontal cortex and increased the glutathione peroxidase
      and glutathione reductase activity in the hippocampus (10mg/kg) and in the
      prefrontal cortex (10-100mg/kg). The long-term treatment with fluoxetine
      (10mg/kg, p.o.), a positive control, was also able to increase the GSH levels in
      the hippocampus, but failed to alter the activity of both enzymes. Besides the
      specific antidepressant-like effect, long-term, but not the acute treatment with
      alpha-T, especially in the doses that produced an antidepressant-like effect
      (10mg/kg), improved the antioxidant defenses in the mouse hippocampus and
      prefrontal cortex, two structures closely implicated in the pathophysiology of
      depression.

PMID- 20144660
TI  - Tagging items in spatial working memory: a unit-recording study in the rat medial
      prefrontal cortex.
AB  - The rat medial prefrontal cortex has been suggested to be involved in executive
      functions and, more specifically, in working memory and response selection. Here,
      we looked for prefrontal neural correlates as rats performed a modified radial
      arm maze task that taxed such functions. Rats had to learn the position of four
      rewarded arms among eight, and visit each rewarded arm only once, thus avoiding
      repeated visits. In addition, rats were left on the maze after the four
      successful visits to baited arms until they had visited all the arms twice.
      Prefrontal neural activity was examined during choice periods, i.e. 2s before the
      rat entered the arms. We found that a substantial proportion of recorded medial
      prefrontal neurons were selectively activated before either the first or second
      visit to the arms irrespective of their reward status, thereby tagging already
      visited arms. These behavioral correlates show that, within the rodent medial
      prefrontal cortex, neuronal populations demonstrate behavioral correlates
      suggestive of its role in guiding prospective search behavior and thus executive
      functions.

PMID- 20144661
TI  - Maternal deprivation-caused behavioral abnormalities in adult rats relate to a
      non-methylation-regulated D2 receptor levels in the nucleus accumbens.
AB  - In this study we investigated the effects of maternal deprivation on adult rats'
      spatial learning and memory, exploratory, and limbic activity and their
      correlations with the gene expression of dopamine transporter (DAT) and dopamine
      D1, D2, D3 receptors (DRD1, DRD2, DRD3) in the nucleus accumbens (NAc). We
      further investigated whether DNA methylation is involved in the regulation of
      DRD2 gene expression. Results from our behavioral tests demonstrated that
      maternal deprivation significantly decreased the spatial learning and memory
      ability, exploratory ability, and limbic activity in adult rats, while results
      from our molecular analysis revealed that the mRNA levels of DAT, DRD1, DRD2, and
      DRD3 were significantly downregulated in maternally deprived rats in comparison
      to control animals. Correlation analysis in the maternally deprived rats
      suggested that downregulated DAT and DRD2 mRNA levels significantly correlated
      with the amount of time required to find the platform, but only DRD2
      significantly correlated with the time spent in target quadrant in the Morris
      water-maze test; DAT, DRD1 and DRD2 mRNA levels significantly correlated with the
      number of vertical activity, but only DRD2 mRNA level significantly correlated
      with total distance in the open field test. Conversely, DRD3 mRNA level did not
      display any correlation with behavioral changes. The methylated CpG levels in the
      promoter region of DRD2 gene and the expression of DNA methyltransferases 1
      (Dnmt1) and 3alpha (Dnmt3alpha) were not significantly changed in maternal
      deprivation group in comparison to the control group. We concluded that
      downregulation of DAT, DRD1 and DRD2 gene expression in the NAc is in response to
      the abnormality in exploratory behaviors; downregulation of DAT and DRD2
      expression is in response to the abnormality in spatial learning; downregulation
      of DRD2 is in response to the abnormality in the spatial memory in maternally
      deprived rats; whereas DRD3 plays no role in these behaviors. DNA methylation
      might not be the mechanism to regulate the mRNA level.

PMID- 20144662
TI  - Environmental factors during early developmental period influence
      psychobehavioral abnormalities in adult PACAP-deficient mice.
AB  - Mice lacking the neuropeptide pituitary adenylate cyclase-activating polypeptide
      (PACAP) (PACAP(-/-)) display behavioral abnormalities, and genetic variants of
      the genes encoding PACAP are associated with schizophrenia. Clinical studies show
      that environmental factors, besides genetic factors, play a key role in etiology
      of many psychiatric disorders. This study examined the effects of environmental
      factors such as short-term social isolation and an enriched environment on
      behavioral abnormalities of PACAP(-/-) mice. Rearing in isolation for 2-weeks
      from 4-weeks old induced hyperlocomotion and aggressive behaviors in the PACAP(-/
      ) mice without affecting the behavioral performance of the wild-type controls.
      Adult PACAP(-/-) mice showed not only hyperactivity, jumping behavior, and
      depression-like behavior, but also decreased social interaction. These abnormal
      behaviors were improved by rearing for 4-weeks in an early enriched environment
      (from 4-weeks old), although the deficits of prepulse inhibition (PPI) were not
      influenced by the enriched condition. In contrast, rearing for 4-weeks in late
      enriched environment (from 8-weeks old) did not affect the hyperactivity and
      jumping behaviors in the PACAP(-/-) mice. These results suggest that abnormal
      behaviors except PPI deficits in PACAP(-/-) mice depend on the environmental
      factors during the early stages of development.

PMID- 20144663
TI  - Proteomic study of activated Taenia solium oncospheres.
AB  - Taenia solium cysticerci are a major cause of human seizures and epilepsy in the
      world. In the gastrointestinal tract of infected individuals, taeniid eggs
      release the oncospheres, which are then activated by intestinal stimuli, getting
      ready to penetrate the gut wall and reach distant locations where they transform
      in cysticerci. Information about oncospheral molecules is scarce, and elucidation
      of the oncosphere proteome could help understanding the host-parasite
      relationship during the first steps of infection. In this study, using liquid
      chromatography and tandem mass spectrometry (LC-MS/MS) analysis, we could
      identify a set of oncospheral proteins involved in adhesion, protein folding,
      detoxification and proteolysis, among others. In addition, we have characterized
      one of the identified molecules, the parasite 14-3-3, by immunoblot and
      immunolocalization. The identification of these oncospheral proteins represents
      the first step to elucidate their specific roles in the biology of the host
      parasite relationship.

PMID- 20144664
TI  - Habituation-sensitization of cardiovascular reactivity to repeated stress in
      smokers and non-smokers: an anthropometrically matched trial.
AB  - Previous research has been equivocal as to the impact of smoking status on
      cardiovascular reactivity to challenge. In addition, little is known about
      patterns of cardiovascular response habituation-sensitization to repeated
      challenge, in either smokers or the general population as a whole. The present
      study sought to clarify whether smokers and non-smokers differ in cardiovascular
      reactivity to challenge, or in patterns of reactivity to repeated challenge. 28
      smokers and 28 anthropometrically matched non-smokers underwent repeated
      cardiovascular reactivity assessment. Results suggest that smokers had higher
      diastolic blood pressure (DBP) than non-smokers, and that female non-smokers
      demonstrated DBP response sensitization. Findings highlight direct associations
      between smoking and cardiovascular reactivity of potential significance to the
      etiology of cardiovascular disease.

PMID- 20144665
TI  - Analytic measures for quantification of arousal from spontaneous skin conductance
      fluctuations.
AB  - Autonomic arousal is often indexed by spontaneous fluctuations in skin
      conductance. Here, we derive a simple measure of sympathetic arousal, using a
      convolution model of how sudomotor bursting causes fluctuations in skin
      conductivity. Under this model, the time-integral of measured conductance is
      proportional to the frequency and amplitude of sudomotor bursts. We demonstrate
      the validity of this measure in relation to finite impulse response models, and
      show that it is a better predictor of autonomic arousal, relative to conventional
      measures.

PMID- 20144666
TI  - Blockade of dorsal hippocampal dopamine receptors inhibits state-dependent
      learning induced by cannabinoid receptor agonist in mice.
AB  - To clarify the interaction between cannabinnoid CB1 receptors and the
      dopaminergic system in memory processes, the effects of dopamine receptor agents
      on the state-dependent learning induced by the non-selective CB1/CB2 receptor
      agonist, WIN55,212-2 have been investigated in mice. Animals implanted with
      unilateral cannula at the CA1 region of the dorsal hippocampus and microinjected
      with WIN55,212-2 and/or dopaminergic agents, were tested using a single-trial
      step-down passive avoidance task. Intra-CA1 microinjections of WIN55,212-2 (0.1-1
      microg/mouse) immediately after training, decreased the step-down latency,
      indicating an amnesic effect of the drug. The amnesia was reversed by pre-test
      administration of the drug, suggesting state-dependent learning by the
      cannabinoid. Pre-test microinjection of apomorphine, a D1/D2 dopamine receptor
      agonist (0.1-0.3 microg/mouse) into the CA1 region reversed the amnesia induced
      by post-training WIN55,212-2 (1 microg/mouse). Moreover, pre-test co
      administration of apomorphine with an ineffective dose of WIN55,212-2 (0.01
      microg/mouse), showed a reversion of the impairment on retention performance. Pre
      test administration of the same doses of apomorphine did not show any response by
      itself. Pre-test intra-CA1 administration of a D1 dopamine receptor antagonist,
      SCH23390 (0.05-0.3 microg/mouse) or D2 dopamine receptor antagonist, sulpiride
      (0.125-0.5 microg/mouse) inhibited the expression of WIN55,212-2-induced state
      dependent learning. Pre-test microinjection of the same doses of SCH23390 or
      sulpiride had no effect on WIN55,212-2-induced amnesia. Moreover, single
      injection of SCH23390 (0.2 and 0.3 microg/mouse) or sulpiride (0.125
      microg/mouse) decreased memory retrieval. The results suggest that the dorsal
      hippocampal dopaminergic system participates in the modulation of WIN55,212-2
      induced state-dependent learning.

PMID- 20144667
TI  - Sex and regional differences in decrease of serotonin-immunoreactive cells by
      parachlorophenylalanine in rat raphe nuclei.
AB  - To determine sex and regional differences in the properties of serotonin (5-HT)
      neurons of the raphe nuclei, the responsiveness to parachlorophenylalanine (PCPA)
      of 5-HT neurons in the dorsal and median raphe nuclei (DR and MR) and the nucleus
      raphe magnus (RMg) was analyzed by counting 5-HT-immunoreactive (5-HT-ir) cells.
      Gonadectomized male (OCX) and female (OVX) rats were treated with 100mg/kg b.wt
      PCPA or saline daily for 4 days. The brains were removed and fixed one day after
      the last injection. Frozen sections were stained with serotonin antibody and the
      numbers of 5-HT-ir cells in the raphe nuclei were counted. As a result, in female
      rats, the densities of 5-HT-ir cells in these 3 raphe nuclei were almost the same
      when compared the PCPA-treated and saline-treated groups. On the other hand, in
      male rats, the densities of 5-HT-ir cells in the DR and MR of PCPA-treated rats
      were lower than in saline-treated rats. In the male RMg, no difference was seen.
      These results suggest that responsiveness of 5-HT neurons to PCPA in the DR and
      MR, but not in the RMg, were sexually dimorphic.

PMID- 20144668
TI  - Structural comparisons of hepatitis B core antigen particles with different C
      terminal lengths.
AB  - Core protein of hepatitis B virus (HBV) with various C-terminal lengths (residue
      154, 164, 167 and 183) can self-assemble into recombinant hepatitis B core
      antigen (HBcAg) particles. To understand the RNA encapsidation mechanism of HBV,
      the three-dimensional structures of these particles were reconstructed by cryo
      electron microscopy (cryoEM). Detailed structural comparisons showed that their
      capsid structures are highly similar, while the RNA content is increased upon the
      retention of more amino acid residues at the C-terminus of core protein,
      suggesting the crucial role of the basic C-terminal tail on determining the
      genome size.

PMID- 20144669
TI  - Acylation of octaarginine: Implication to the use of intracellular delivery
      vectors.
AB  - Cell-penetrating peptides (CPPs) have the ability to efficiently internalize into
      cells and thus have been used as a vector for the intracellular delivery of
      various bioactive molecules. The introduction of a hydrophobic core to CPPs may
      increase their interaction with membranes and facilitate their translocation into
      cells. While the usefulness of acylated oligoarginine to gene and siRNA delivery
      has been largely reported, little information is available about their use for
      the delivery of small molecular-weight compounds, peptides and proteins. In this
      report, we employed octaarginine (R8) as a typical arginine-rich CPP and
      evaluated the effect of acylation using butanoic, hexanoic and decanoic acids on
      its capacity as a delivery vector. Hexanoyl octaarginine (C6R8-Alexa) showed the
      highest efficiency of cellular uptake of the studied variants, ten times higher
      than R8-Alexa. C6R8-Alexa also produced a diffuse cytosolic distribution. On the
      other hand, a less significant effect of C6R8 over R8 was observed for the
      delivery of proteins, suggesting that the advantage of C6R8 may be obtained
      during the delivery of relatively small molecular-weight compounds. Although less
      prominent than at 37 degrees C, a significant cytosolic distribution of C6R8
      Alexa was observed at 4 degrees C, and this suggested the potential ability of
      the C6R8 peptide for direct penetration through plasma membranes.

PMID- 20144670
TI  - Pegylated immuno-lipopolyplexes: A novel non-viral gene delivery system for liver
      cancer therapy.
AB  - In this study, pegylated immuno-lipopolyplexes (PILP), a novel and efficient gene
      delivery system was developed by employing DNA/polyethylenimine (PEI 25 kDa)
      polyplexes, as well as anionic liposomes composed of POPC, (DSPE)-PEG2000 and
      (DSPE)-PEG2000-biotin, at five different lipid/DNA molar ratios (50/1, 90/1,
      130/1, 170/1 and 210/1), and by using streptavidin-monoclonal antibody
      conjugating through the biotin group located at the distal end of the PEG spacer
      as targeting antibody. This vector was highly effective in protecting DNA from
      enzyme digestion, and stable in particle size and zeta potential even after 20
      day-storage at 4 degrees C. At the lipid/DNA molar ratio 170/1, the PILP were
      found to have the highest in vitro transfection efficiency with an average
      particle size of 132 nm and an average zeta potential of +9.5 mV. These complexes
      showed high efficiency in gene delivery to liver cancer cells with no significant
      cytotoxicity. Interestingly, the in vitro transfection efficiency did not
      decrease significantly up to 10 days of storage of PILP at 4 degrees C.
      Intravenous administration of the PILP resulted in tumor and liver targeted gene
      expression of the reporter genes EGFP and luciferase as opposed to the lung
      targeted gene expression obtained with PEI/DNA complexes, causing no cytokine
      production and liver injury. We conclude that the PILP are promising gene
      delivery systems which may be used to target the liver cancer.

PMID- 20144671
TI  - Differences in satiety effects of alginate- and whey protein-based foods.
AB  - Satiety is important in regulating food intake and has important public health
      significance in the control of obesity. Food containing protein and non-starch
      polysaccharides provides a satiety effect through various mechanisms but a
      comparison of the satiety effect on each has not previously been investigated.
      This study compared the satiety effect or reduction of hunger after consumption
      of (i) a whey protein-based drink versus an alginate-based drink of the same
      viscosity where only the protein content differed, (ii) two alginate-based drinks
      differing in alginate type and viscosity, and (iii) a whey protein-based drink
      versus an alginate-based drink differing in protein content and viscosity. Fasted
      subjects assessed the effect of a drink on hunger that was one of three variants:
      a low viscosity whey protein drink (LVHP); a high viscosity low protein alginate
      based drink (HVLP); or a low viscosity low protein alginate-based drink (LVLP)
      over the 240 min postprandial period using a Visual Analogue Scale (VAS). When
      protein differed and viscosity was the same, results showed subjects felt
      significantly less hungry after consuming the LVHP drink compared to the LVLP
      drink, so protein reduced hunger. Subjects reported reduced hunger from the HVLP
      drink compared to the LVLP drink where viscosity of drinks differed, suggesting
      viscosity and/or gelation reduced hunger. Subjects reported reduced hunger from
      the HVLP drink compared to LVHP drink where both protein and viscosity differed,
      suggesting that viscosity reduced hunger more than the protein effect. Results
      suggest the physical characteristics such as viscosity and/or gel strength and
      protein content reduce hunger. Further studies should investigate which of these
      parameters is more important.

PMID- 20144672
TI  - Chloride channel conductance is required for NGF-induced neurite outgrowth in
      PC12 cells.
AB  - We have previously shown that in PC12 cells: (1) high extracellular KCl induces
      moesin phosphorylation, an event which was dependent on chloride channel
      activation, and (2) NGF induces moesin phosphorylation which is required for
      neurite outgrowth. These results suggest that NGF-induced intracellular signaling
      and neurite outgrowth is also mediated by activation of anion channels. Using a
      patch-clamp technique, we found that NGF treatment increased anionic conductance
      in PC12 cells, an effect which was completely blocked by NPPB, a chloride channel
      inhibitor. Also, the NGF-induced moesin phosphorylation was suppressed by NPPB.
      Additionally, NPPB and SITS, another chloride channel blocker, suppressed NGF
      induced TrkA phosphorylation and subsequent PI3K/Akt phosphorylation and Rac1
      activation in PC12 cells. Moreover, the chloride channel inhibitors also
      suppressed the neurite outgrowth and decreased the cell viability in response to
      long-term treatment of NGF. In summary, our results suggest that chloride ion
      flux plays an important role in TrkA-mediated signaling pathway during NGF
      induced differentiation of PC12 cells.

PMID- 20144673
TI  - Physiology of neuronal-glial networking.
AB  - Neuronal-glial networks are the substrate for the brain function. Evolution of
      the nervous system resulted in the appearance of highly specialized neuronal web
      optimized for rapid information transfer. This neuronal web is embedded into
      glial syncytium, thereby creating sophisticated neuronal-glial circuitry were
      both types of neural cells are working in concert, ensuring amplification of
      brain computational power. In addition neuroglial cells are fundamental for
      control of brain homeostasis and they represent the intrinsic brain defence
      system, being thus intimately involved in pathogenesis of neurological diseases.

PMID- 20144674
TI  - Identification of a novel chemical potentiator and inhibitors of UCH-L1 by in
      silico drug screening.
AB  - Ubiquitin-C-terminal hydrolase L1 (UCH-L1) is a de-ubiquitinating enzyme
      expressed in the brain and reproductive tissues as well as certain cancers. The
      hydrolase activity of UCH-L1 has been implicated in Alzheimer's disease and
      cancer invasion; therefore, it may represent a therapeutic target for these
      diseases. The present study was undertaken to identify novel chemical modulators
      for the hydrolase activity of UCH-L1. To identify chemicals that bind to the
      active site of UCH-L1, we carried out in silico structure-based drug screening
      using human UCH-L1 crystal structure data (PDB ID: 2ETL) and virtual compound
      libraries containing 26,891 and 304,205 compounds. Among the compounds with the
      highest binding scores, we identified one that potentiates the hydrolase activity
      of UCH-L1, and six that inhibit the activity in enzymatic assays. These compounds
      may be useful for research on UCH-L1 function, and could lead to candidate
      therapeutics for UCH-L1-associated diseases.

PMID- 20144675
TI  - Induced LC degeneration in APP/PS1 transgenic mice accelerates early cerebral
      amyloidosis and cognitive deficits.
AB  - Degeneration of locus ceruleus neurons and subsequent reduction of norepinephrine
      concentration in locus ceruleus projection areas represent an early pathological
      indicator of Alzheimer's disease. In order to model the pathology of the human
      disease and to study the effects of norepinephrine-depletion on amyloid precursor
      protein processing, behaviour, and neuroinflammation, locus ceruleus degeneration
      was induced in mice coexpressing the swedish mutant of the amyloid precursor
      protein and the presenilin 1 DeltaExon 9 mutant (APP/PS1) using the neurotoxin N
      (2-chloroethyl)-N-ethyl-bromo-benzylamine (dsp4) starting treatment at 3 months
      of age. Norepinephrine transporter immunolabelling demonstrated severe loss of
      locus ceruleus neurons and loss of cortical norepinephrine transporter starting
      as early as 4.5 months of age and aggravating over time. Of note, dsp4-treated
      transgenic mice showed elevated amyloid beta levels and impaired spatial memory
      performance at 6.5 months of age compared to control-treated APP/PS1 transgenic
      mice, indicating an accelerating effect on cerebral amyloidosis and cognitive
      deficits. Likewise, norepinephrine-depletion increased neuroinflammation compared
      to transgenic controls as verified by macrophage inflammatory protein-1alpha and 
      1beta gene expression analysis. Exploratory activity and memory retention was
      compromised by age in APP/PS1 transgenic mice and further aggravated by induced
      noradrenergic deficiency. In contrast, novel object recognition was not
      influenced by norepinephrine deficiency, but by the APP/PS1 transgene at 12
      months. Overall, our data indicate that early loss of noradrenergic innervation
      promotes amyloid deposition and modulates the activation state of inflammatory
      cells. This in turn could have had impact on the acceleration of cognitive
      deficits observed over time.

PMID- 20144676
TI  - UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells
      over-expressing P2Y6 receptor.
AB  - The role of P2 receptors for purines/pyrimidines is not well characterized in
      neuroblastoma, although a variety of purinergic mRNAs/proteins are expressed in
      these cells. Among these, the P2Y(6) receptor is the only subtype distinguished
      by UDP-specific activation. In this work, after over-expressing the P2Y(6)
      protein in human neuroblastoma SH-SY5Y cells, we find that UDP arrests cell cycle
      and induces apoptosis, by counteracting the pathological functioning of
      neuroblastoma in vitro. UDP also causes mitochondrial damage through diffusion of
      cytochrome c in the cytoplasm, and stimulates caspase-3,7,8 activities, with
      extensive over-expression of manganese superoxide dismutase. Our data establish
      the direct toxic role and anti-cancer activity of UDP in a neuroblastoma cell
      line, and identify the P2Y(6) receptor as a novel potential target in anti
      tumoural therapies. This constitutes an advancement not only in the knowledge of
      purinergic signalling, but also in the biological and pathological aspects of
      neuroblastoma in vitro.

PMID- 20144677
TI  - No association between EGR gene family polymorphisms and schizophrenia in the
      Chinese population.
AB  - Early growth response (EGR) genes are thought to have a role in the pathogenesis
      of schizophrenia because of their conserved DNA binding domain and biologically
      activity in neuronal plasticity. This zinc-finger motif could influence gene post
      translational modification and expression. The multigenetic association model,
      using markers in genes of similar or antagonistic biological effects within a
      signal pathway or gene family, might be more appropriate to this aspect of the
      schizophrenia hypothesis than the single gene strategy. In this study we
      investigated the role of EGR1, EGR2, EGR3 and EGR4 within the EGR family. Taqman
      technology was used to examine 12 single nucleotide polymorphisms (SNPs) covering
      these four genes in 2044 Chinese Han subjects. Case-control analyses were
      performed to detect association of these 4 genes with schizophrenia and
      multifactor dimensionality reduction (MDR) analysis was employed to examine their
      potential gene-gene interaction in schizophrenia. Neither allelic nor genotypic
      single-locus tests revealed any significant association between EGR1-4 and the
      risk of schizophrenia nor was any such association found with regard to
      interaction within EGR1-4 (p(min)=0.623, CV Consistency=10/10). We concluded that
      although multiple candidate genes are involved in schizophrenogenic development,
      the EGR family may not play a major role in schizophrenia susceptibility in the
      Chinese Han population.

PMID- 20144678
TI  - Type-IIA secreted phospholipase A2 is an endogenous antibiotic-like protein of
      the host.
AB  - Type-IIA secreted phospholipase A(2) (sPLA(2)-IIA) has been proposed to play a
      role in the development of inflammatory diseases. It has been shown to release
      arachidonic acid, the precursor of proinflammatory eicosanoids, to hydrolyze
      phospholipids of pulmonary surfactant, and to bind to specific receptors located
      on cell surface membranes. However, the most established biological role of
      sPLA(2)-IIA is related to its potent bactericidal property in particular toward
      Gram-positive bacteria. This enzyme is present in animal and human biological
      fluids at concentrations sufficient to kill bacteria. Human recombinant sPLA(2)
      IIA is able to kill Gram-positive bacteria at concentrations as low as 1.1 ng/ml.
      This remarkable property is due to the unique preference of sPLA(2)-IIA for
      anionic phospholipids such as phosphatidylglycerol, the main phospholipid
      component of bacterial membranes. Much higher concentrations of sPLA(2)-IIA are
      required for its action on host cell membranes and surfactant both of which are
      mainly composed by phosphatidylcholine, a poor substrate for sPLA(2)-IIA.
      Transgenic mice over-expressing human sPLA(2)-IIA are resistant to infection by
      Staphylococcus aureus, Escherichia coli, and Bacillus anthracis, the etiological
      agent of anthrax. Conversely, certain bacteria, such as B. anthracis, E. coli and
      Bordetella pertussis are able to inhibit sPLA(2)-IIA expression by host cells,
      thus highlighting a mechanism by which these bacteria can subvert the host immune
      system. Intranasal instillation of recombinant sPLA(2)-IIA protects mice from
      mortality caused by pulmonary anthrax. Interestingly, this protective effect was
      obtained even with B. anthracis strains that down-regulate the expression of
      endogenous sPLA(2)-IIA, indicating that instilled sPLA(2)-IIA can overcome the
      subversive action of B. anthracis. We conclude that sPLA(2)-IIA is an efficient
      endogenous antibiotic of the host and can play a role in host defense against
      pathogenic bacteria. It can be used as a therapeutic agent in adjunct with
      current therapy to treat bacteria resistant to multiple antibiotics.

PMID- 20144679
TI  - Filamentous actin and its associated binding proteins are the stimulatory site
      for 6-phosphofructo-1-kinase association within the membrane of human
      erythrocytes.
AB  - Glycolytic enzymes reversibly associate with the human erythrocyte membrane (EM)
      as part of their regulatory mechanism. The site for this association has been
      described as the amino terminus of band 3, a transmembrane anion transporter.
      Binding of glycolytic enzymes to this site is recognized to inhibit glycolysis,
      since binding inhibits the catalytic activity of these enzymes, including the
      rate-limiting enzyme 6-phosphofructo-1-kinase (PFK). However, the existence of a
      putative stimulatory site for glycolytic enzymes within the EM has been proposed.
      PFK has been described as able to reversibly associate with other proteins, such
      as microtubules, which inhibit the enzyme, and filamentous actin, which activates
      the enzyme. Here, it is demonstrated that PFK also binds to actin filaments and
      its associated binding proteins in the protein meshwork that forms the
      erythrocyte cytoskeleton. Through fluorescence resonance energy transfer
      experiments using either confocal microscopy or fluorescence spectroscopy, we
      show that, within the EM, PFK and actin filaments containing its associated
      binding proteins are located close enough to propose binding between them.
      Moreover, specifically blocking PFK binding to band 3 results in an association
      of the enzyme with the EM that increases the enzyme's catalytic activity.
      Conversely, disruption of the association between PFK and actin filaments
      containing its associated binding proteins potentiates the inhibitory action of
      the EM on the enzyme. Furthermore, it is shown that insulin signaling increases
      the association of PFK to actin filaments and its associated binding proteins,
      revealing that this event may play a role on the stimulatory effects of insulin
      on erythrocyte glycolysis. In summary, the present work presents evidence that
      filamentous actin and its associated binding proteins are the stimulatory site
      for PFK within the EM.

PMID- 20144680
TI  - LysK, the enzyme lysing Staphylococcus aureus cells: specific kinetic features
      and approaches towards stabilization.
AB  - LysK, the enzyme lysing cells of Staphylococcus aureus, can be considered as
      perspective antimicrobial agent. Knowledge of LysK properties and behavior would
      allow optimizing conditions of its storage as well as formulating strategy
      towards its stabilization. Reaction of LysK with substrate (suspension of
      autoclaved Staphylococcus aureus cells) has been found to be adequately described
      by the two-stage Michaelis-Menten kinetic scheme. Ionization of the enzyme and
      enzyme-substrate complex is important for revealing catalytic activity, which is
      controlled by two ionogenic groups with pK 6.0 and 9.6. Ionization energy of the
      group with pK 6.0 is of 30 kJ/mol, thus, pointing out on His residue; pK 9.6
      might be attributed to metal ion or metal-bound water molecule. At temperatures
      lower than 40 degrees C, LysK stability depends on its concentration, pH and
      presence of low molecular weight additives. Results of electrophoresis under
      native and denaturing conditions as well as sedimentation analysis strongly
      suggest that aggregation is behind LysK inactivation. Decrease in the enzyme
      concentration, as well as addition of low molecular mass polyols (glycerol,
      sorbitol, sucrose, trehalose) and Ca(2+) cations resulted in an enhanced (more
      than 100 times) stability of LysK. Dramatic stability decline observed in a
      narrow temperature range (40-42 degrees C) was accompanied by changes in LysK
      secondary structure as confirmed by CD spectroscopy studies. According to
      computer modeling data, Cys and His residues and metal cation might play a
      crucial role for LysK catalytic activity. Our data on the enzyme activity in the
      presence of ethylenediaminetetraacetic acid and different metal cations confirmed
      the importance of metal cation in LysK catalysis.

PMID- 20144681
TI  - Serum response factor depletion affects the proliferation of the hepatocellular
      carcinoma cells HepG2 and JHH6.
AB  - For hepatocellular carcinoma (HCC), a leading cause of cancer death world-wide,
      there is no effective therapy especially for the advanced stage of the disease.
      Thus, we started the investigations about a novel anti HCC approach based on the
      depletion of the transcription factor serum response factor (SRF) in HCC cell
      lines; SRF choice was based on its recently proposed contribution to HCC tissue
      development and on its important role in cell proliferation. SRF depletion,
      obtained by a siRNA (siSRF797), was studied in two HCC cell lines, i.e. HepG2 and
      JHH6 assigned to high and low hepatocytic differentiation grade on the base of
      the capacity to synthesize albumin. In the HCC cell lines examined, siSRF797
      reduced both the mRNA and protein levels of SRF without inducing unspecific
      interferon response or cytotoxicity. Moreover, SRF depletion induced the
      reduction of S-phase cells and a decrease in cell number and vitality.
      Particularly in HepG2, cell growth impairment was paralleled by the decrease of
      the levels of the transcription factor E2F1 together with some of its regulated
      genes. In HepG2 but not in JHH6, SRF depletion was associated with apoptosis.
      Finally, in both HepG2 and JHH6, the combined administration of siSRF797 and
      bortezomib, a proteasome inhibitor whose therapeutic potential for HCC is
      considered attractive, further reduced cell viability compared to either siSRF797
      or bortezomib treatment alone. In conclusion, SRF depletion affects the expansion
      of the high and low differentiation grade HCC cells HepG2 and JHH6. These results
      can pave the way to understand the role of SRF in HCC development and possibly to
      identify novel anti HCC therapeutic strategies.

PMID- 20144682
TI  - Change point analysis for longitudinal physiological data: detection of cardio
      respiratory changes preceding panic attacks.
AB  - Statistical methods for detecting changes in longitudinal time series of
      psychophysiological data are limited. ANOVA and mixed models are not designed to
      detect the existence, timing, or duration of unknown changes in such data. Change
      point (CP) analysis was developed to detect distinct changes in time series data.
      Preliminary reports using CP analysis for fMRI data are promising. Here, we
      illustrate the application of CP analysis for detecting discrete changes in
      ambulatory, peripheral physiological data leading up to naturally occurring panic
      attacks (PAs). The CP method was successful in detecting cardio-respiratory
      changes that preceded the onset of reported PAs. Furthermore, the changes were
      unique to the pre-PA period, and were not detected in matched non-PA control
      periods. The efficacy of our CP method was further validated by detecting
      patterns of change that were consistent with prominent respiratory theories of
      panic positing a relation between aberrant respiration and panic etiology.

PMID- 20144683
TI  - HPA axis, respiration and the airways in stress--a review in search of
      intersections.
AB  - Given clear connections between respiratory distress and subjective anxiety, it
      is not surprising that respiratory psychophysiologists have been interested in
      the psychobiology of anxiety. Given parallel links between anxiety and stress, it
      is not surprising that the hypothalamic-pituitary adrenal (HPA) stress system has
      also been a focus in anxiety research. However, despite extensive work in
      respiratory psychophysiology and stress neuroendocrinology--and evidence that
      these systems are jointly dysregulated in anxiety disorders--direct studies of
      their interactions are rare. This paper reviews evidence for scientific
      intersections, providing an overview of the HPA axis, its psychobiology, and
      shared neural substrates for HPA and respiratory control. We examine HPA hormone
      effects on respiration, immune/inflammatory mediators, and lung maturation. We
      also examine respiratory/dyspnea effects on HPA axis. There are clear points of
      intersection in the neuroscience of respiration and stress. Given the importance
      of both systems to an organism's ability to survive and adapt in challenging and
      changing environments, further study of their interactions is needed.

PMID- 20144684
TI  - Characterization of the norepinephrine-activation of adenylate cyclase suggests a
      role in memory affirmation pathways. Overexposure to epinephrine inactivates
      adenylate cyclase, a causal pathway for stress-pathologies.
AB  - Incubation with noradrenaline (norepinephrine) of isolated membranes of rat's
      brain corpus striatum and cortex, showed that ionic-magnesium (Mg(2+)) is
      required for the neurotransmitter activatory response of adenylate cyclase [ATP
      pyrophosphate-lyase (cyclizing) (EC 4.6.1.1)], AC. An Mg(2+)-dependent response
      to the activatory effects of adrenaline, and subsequent inhibition by calcium,
      suggest capability for a turnover, associated with cyclic changes in membrane
      potential and participation in a short-term memory pathway. In the cell, the
      neurotransmitter by activating AC generates intracellular cyclic AMP. Calcium
      entrance in the cell inhibits the enzyme. The increment of cyclic AMP activates
      kinase A and their protein phosphorylating activity, allowing a long-term memory
      pathway. Hence, consolidating neuronal circuits, related to emotional learning
      and memory affirmation. The activatory effect relates to an enzyme-noradrenaline
      complex which may participate in the physiology of the fight or flight response,
      by prolonged exposure. However, the persistence of an unstable enzyme complex
      turns the enzyme inactive. Effect concordant, with the observation that prolonged
      exposure to adrenaline, participates in the etiology of stress triggered
      pathologies. At the cell physiological level AC responsiveness to hormones could
      be modulated by the concentration of chelating metabolites. These ones produce
      the release of free ATP(4-), a negative modulator of AC and the Mg(2+) activated
      insulin receptor tyrosine kinase (IRTK), thus, allowing an integration of the
      hormonal response of both enzymes by ionic controls. This effect could supersede
      the metabolic feedback control by energy charge. Accordingly, maximum hormonal
      response of both enzymes, to high Mg(2+) and low free ATP(4-), allows a
      correlation with the known effects of low caloric intake increasing average life
      expectancy.

PMID- 20144685
TI  - Mitochondrial dysfunction is induced by high levels of glucose and free fatty
      acids in 3T3-L1 adipocytes.
AB  - Hyperglycemia and high free fatty acids (FFAs) are two well-known characteristics
      of type 2 diabetes, and are also implicated in the etiology of insulin
      resistance. However, their roles in mitochondrial dysfunction of white adipocytes
      are not well-studied. In this study, we investigated the effects of high glucose
      (25 mM), high free fatty acids (FFAs, 1mM), or a combination of both high
      glucose+high FFAs on mitochondrial function in differentiated 3T3-L1 adipocytes
      after 48 h of treatment. We found that high glucose, high FFAs, or high
      glucose+high FFAs reduced insulin-stimulated glucose uptake in differentiated 3T3
      L1 adipocytes. In addition, the mitochondria became smaller and more compact.
      Levels of the mitofusion protein mfn1 decreased and levels of the mitofission
      protein Drp1 increased as compared to controls. NRF1 was downregulated, and PGC-1
      beta levels were diminished in the high glucose and high glucose+high FFAs
      conditions. Levels of PGC-1 alpha and mtTFA mRNA were greatly downregulated. No
      difference was found in the mitochondrial DNA (mtDNA) and intracellular ATP
      levels of treated cells compared to control cells. Cells treated with high
      glucose or high FFAs accumulated significant amounts of reactive oxygen species
      (ROS) and displayed a loss of the mitochondrial membrane potential. High glucose
      and high glucose+high FFAs led to similar decreases in intramitochondrial calcium
      concentration, although high FFAs had no effect. Therefore, high glucose and high
      FFAs can regulate insulin sensitivity, and mitochondrial dysfunction may occur in
      this process.

PMID- 20144686
TI  - Progesterone inhibits apoptosis in part by PGRMC1-regulated gene expression.
AB  - Progesterone receptor membrane component-1 (PGRMC1) is present in both the
      cytoplasm and nucleus of spontaneously immortalized granulosa cells (SIGCs).
      PGRMC1 is detected as a monomer in the cytoplasm and a DTT-resistant PGRMC1 dimer
      in the nucleus. Transfected PGRMC1-GFP localizes mainly to the cytoplasm and does
      not form a DTT-resistant dimer. Moreover, forced expression of PGRMC1-GFP
      increases the sensitivity of the SIGCs to progesterone (P4)'s anti-apoptotic
      action, indicating that the PGRMC1 monomer is functional. However, when
      endogenous PGRMC1 is depleted by siRNA treatment and replaced with PGRMC1-GFP, P4
      responsiveness is not enhanced, although overall levels of PGRMC1 are increased.
      P4's anti-apoptotic action is also attenuated by actinomycin D, an inhibitor of
      RNA synthesis, and P4 activation of PGRMC1 suppresses Bad and increases Bcl2a1d
      expression. Taken together, the present studies suggest a genomic component to
      PGRMC1's anti-apoptotic mechanism of action, which requires the presence of the
      PGRMC1 dimer.

PMID- 20144688
TI  - Common genetic variations in TPH1/TPH2 genes are not associated with
      schizophrenia in Japanese population.
AB  - Alteration of serotonin transmission in the brain of patients with schizophrenia
      has been reported in postmortem brain studies, cerebrospinal fluid studies, and
      pharmacological challenges. Although a genetic association of tryptophan
      hydroxylase isoform 1 (TPH1), the rate-limiting enzyme in serotonin synthesis,
      with schizophrenia has been suggested by recent systematic meta-analyses, the
      newly identified neuronal isoform TPH2 is more relevant to the central nervous
      system and the association of TPH2 gene with schizophrenia has been much less
      explored. We, therefore, explored the association of TPH2 gene with schizophrenia
      using a case-control study of 720 Japanese populations and also tried to
      replicate the association of the TPH1 rs1800532 (A218C) single nucleotide
      polymorphism (SNP) with schizophrenia. We selected 15 tagging SNPs in the TPH2
      gene. We found no significant differences in genotypic distributions (uncorrected
      P=0.18-0.98) or allelic frequencies (uncorrected P=0.18-0.98) of the 15 SNPs
      between the schizophrenia and control groups. Haplotypes constructed with these
      SNPs were also not associated with schizophrenia (uncorrected P=0.12-0.97). The
      genotypic and allelic distribution of the TPH1 rs1800532 SNP was also not
      different between the case and control groups in our samples. In addition, a
      subsequent meta-analysis including our results did not showed a significant
      association with schizophrenia in Asian populations. Our findings suggest that
      neither common genetic variations of TPH1 nor TPH2 are likely to contribute to
      the genetic susceptibility to schizophrenia in Japanese population.

PMID- 20144687
TI  - Genetic determinants of pubertal timing in the general population.
AB  - Puberty is an important developmental stage during which reproductive capacity is
      attained. The timing of puberty varies greatly among healthy individuals in the
      general population and is influenced by both genetic and environmental factors.
      Although genetic variation is known to influence the normal spectrum of pubertal
      timing, the specific genes involved remain largely unknown. Genetic analyses have
      identified a number of genes responsible for rare disorders of pubertal timing
      such as hypogonadotropic hypogonadism and Kallmann syndrome. Recently, the first
      loci with common variation reproducibly associated with population variation in
      the timing of puberty were identified at 6q21 in or near LIN28B and at 9q31.2.
      However, these two loci explain only a small fraction of the genetic contribution
      to population variation in pubertal timing, suggesting the need to continue to
      consider other loci and other types of variants. Here we provide an update of the
      genes implicated in disorders of puberty, discuss genes and pathways that may be
      involved in the timing of normal puberty, and suggest additional avenues of
      investigation to identify genetic regulators of puberty in the general
      population.

PMID- 20144689
TI  - Effects of pioglitazone on diffusion tensor imaging indices in multiple sclerosis
      patients.
AB  - Pioglitazone is an FDA-approved peroxisome proliferator activated receptor gamma
      (PPARgamma) agonist. We tested the hypothesis that treatment with pioglitazone
      reduces new lesion development in patients with RRMS. Twenty-two patients were
      treated with pioglitazone or placebo and monitored by diffusion tensor imaging
      (DTI) at baseline and after 12 months. A negative correlation was found between
      the 1-year change in relative anisotropy (RA) and fluid attenuated inversion
      recovery (FLAIR) lesion burden in the pioglitazone group. Regions of interest
      (ROIs) having high ADC and low RA values at baseline had a significantly higher
      chance to develop into lesions in the placebo group than similar ROIs in the
      pioglitazone group. These findings suggest that baseline DTI parameters can
      provide a prognostic surrogate marker for lesions, and that pioglitazone can
      reduce conversion of normal appearing white matter to lesions.

PMID- 20144690
TI  - Age-related changes in HSP25 expression in basal ganglia and cortex of F344/BN
      rats.
AB  - Normal aging is associated with chronic oxidative stress. In the basal ganglia,
      oxidative stress may contribute to the increased risk of Parkinson's disease in
      the elderly. Neurons are thought to actively utilize compensatory defense
      mechanisms, such as heat shock proteins (HSPs), to protect from persisting
      stress. Despite their protective role, little is known about HSP expression in
      the aging basal ganglia. The purpose of this study was to examine HSP expression
      in striatum, substantia nigra, globus pallidus and cortex in 6-, 18- and 30-month
      old Fischer 344/Brown Norway rats. We found robust age-related increases in
      phosphorylated and total HSP25 in each brain region studied. Conversely, HSP72
      (the inducible form of HSP70) was reduced with age, but only in the striatum. p38
      MAPK, a protein implicated in activating HSP25, did not change with age, nor did
      HSC70 (the constitutive form of HSP70), or HSP60. These results suggest that
      HSP25 is especially responsive to age-related stress in the basal ganglia.

PMID- 20144691
TI  - Specific inhibitory effect of amyloid-beta on presynaptic muscarinic receptor
      subtypes modulating neurotransmitter release in the rat nucleus accumbens.
AB  - In this study we investigate on the effect of amyloid-beta1-40 (A beta 1-40) on
      the oxotremorine (OXO)-induced release of [(3)H] dopamine (DA), [(3)H]GABA and
      [(3)H]acetylcholine (ACh) from synaptosomes in the rat nucleus accumbens (NAc).
      OXO in presence of himbacine (HIMBA) was able to increase the basal release of
      [(3)H]GABA. The OXO-elicited [(3)H]GABA overflow was significantly antagonized by
      atropine (A; 94%), by the M3 antagonists DAU5884 (96%) and 4-DAMP (70%), and by A
      beta 1-40 (65%). Exposure of NAc synaptosomes to OXO produced a dose-dependent
      increase of [(3)H]DA overflow which was antagonized by A, partially inhibited by
      A beta 1-40 (100 nM) but unaffected by DAU5884 and 4-DAMP. The K(+)-evoked
      [(3)H]ACh overflow was inhibited by OXO. This effect was counteracted by the M2
      antagonist AFDX-116 but not by the selective M4 antagonist mamba toxin 3 (MT3).
      The K(+)-evoked [(3)H]GABA overflow was also inhibited by OXO but conversely,
      this effect was counteracted by MT3 and not by AFDX-116. A beta 1-40 (100 nM) did
      not modify the inhibitory effect of OXO both on the K(+)-evoked [(3)H]ACh and
      [(3)H]GABA overflow. The results show that in the rat NAc, A beta 1-40
      selectively inhibits the function of the muscarinic subtypes which stimulate
      neurotransmitter release and not those which modulate negatively the stimulated
      release.

PMID- 20144692
TI  - Unilateral low frequency versus sequential bilateral repetitive transcranial
      magnetic stimulation: is simpler better for treatment of resistant depression?
AB  - Repetitive transcranial magnetic stimulation (rTMS) efficacy in the treatment of
      major depression has been shown in both low frequency right-sided and high
      frequency left-sided stimulation over the dorsolateral prefrontal cortex (DLPFC).
      The aim of the present investigation was to evaluate the hypothesis of an
      additive effect of bilateral stimulation compare to sequential to unilateral
      stimulation. Sixty patients with treatment-resistant depression were assigned to
      receive either low-frequency rTMS over the right DLPFC (140 s x 1 Hz) followed by
      controlateral sham (unilateral group, n=20), low frequency right DLPFC rTMS
      followed by left DLPFC high frequency rTMS (5 s x 10 Hz) (bilateral group, n=20),
      or bilateral sham (sham group, n=20) in a 3 weeks double-blind, randomized trial.
      The primary outcome variable was the score on Hamilton Depression Scale (HAM-D).
      Low frequency right-sided and sequential bilateral stimulation showed different
      antidepressant efficacy at 3 weeks and across the full duration of the study,
      only the unilateral method appearing significantly more effective than sham at
      the end of the trial, and correlated to the higher percent of remitters (30% of
      the group vs. 10% -bilateral- and 5% -sham). Unilateral stimulation, but not
      bilateral, showed higher antidepressant efficacy compared to sham stimulation.
      The data suggest that right-sided low frequency stimulation may be a first line
      treatment alternative in resistant depression. To confirm and extend these
      findings further studies require a longer follow-up period, supported by
      biological observation and replication.

PMID- 20144694
TI  - Persistent genital arousal disorder associated with functional hyperconnectivity
      of an epileptic focus.
AB  - Persistent Genital Arousal Disorder (PGAD) refers to the experience of persistent
      sensations of genital arousal that are felt to be unprovoked, intrusive and
      unrelieved by one or several orgasms. It is often mistaken for hypersexuality
      since PGAD often results in a high frequency of sexual behaviour. At present
      little is known with certainty about the etiology of this condition. We described
      a woman with typical PGAD symptoms and orgasmic seizures that we found to be
      related to a specific epileptic focus. We performed a EEG/MEG and fMRI
      spontaneous activity study during genital arousal symptoms and after the chronic
      administration of 300 mg/day of topiramate. From MEG data an epileptic focus was
      localized in the left posterior insular gyrus (LPIG). FMRI data evidenced that
      sexual excitation symptoms with PGAD could be correlated with an increased
      functional connectivity (FC) between different brain areas: LPIG (epileptic
      focus), left middle frontal gyrus, left inferior and superior temporal gyrus and
      left inferior parietal lobe. The reduction of the FC observed after antiepileptic
      therapy was more marked in the left than in the right hemisphere in agreement
      with the lateralization identified by MEG results. Treatment completely abolished
      PGAD symptoms and functional hyperconnectivity. The functional hyperconnectivity
      found in the neuronal network including the epileptic focus could suggest a
      possible central mechanism for PGAD.

PMID- 20144693
TI  - Gene expression profiling following short-term and long-term morphine exposure in
      mice uncovers genes involved in food intake.
AB  - Addictive drugs including opioids activate signal transduction pathways that
      regulate gene expression in the brain. However, changes in CNS gene expression
      following morphine exposure are poorly understood. We determined changes in gene
      expression following short- and long-term morphine treatment in the hypothalamus
      and pituitary using genome-wide DNA microarray analysis and confirmed those
      alterations in gene expression by real-time reverse transcriptase polymerase
      chain reaction (RT-PCR) analysis. In the hypothalamus, short-term morphine
      administration up-regulated (at least twofold) 39 genes and down-regulated six
      genes. Long-term morphine treatment up-regulated 35 genes and down-regulated 51
      genes. In the pituitary, short-term morphine administration up-regulated 110
      genes and down-regulated 29 genes. Long-term morphine treatment up-regulated 85
      genes and down-regulated 37 pituitary genes. Microarray analysis uncovered
      several genes involved in food intake (neuropeptide Y, agouti-related protein,
      and cocaine and amphetamine-regulated transcript) whose expression was strongly
      altered by morphine exposure in either the hypothalamus or pituitary. Subsequent
      RT-PCR analysis confirmed similar regulation in expression of these genes in the
      hypothalamus and pituitary. Finally, we found functional correlation between
      morphine-induced alterations in food intake and regulation of genes involved in
      this process. Changes in genes related to food intake may uncover new pathways
      related to some of the physiological effects of opioids.

PMID- 20144695
TI  - Automatic brain response to facial emotion as a function of implicitly and
      explicitly measured extraversion.
AB  - Extraversion/introversion is a basic dimension of personality that describes
      individual differences in social behavior and sensory sensitivity. Previous
      neuroimaging research exclusively relied on self reports for assessing
      personality traits. In recent years, implicit measures of personality have been
      developed that aim at assessing the implicit self-concept of personality and
      complement self report instruments which are thought to measure aspects of the
      explicit self-concept of personality. In the present study functional magnetic
      resonance imaging was used to examine automatic brain reactivity to facial
      expression as a function of both implicitly and explicitly measured extraversion
      in 30 healthy women. Sad, happy, and neutral faces were presented for 33 ms
      masked by neutral faces beside a no face control condition. Subjects evaluated
      the briefly shown neutral mask faces. The Implicit Association Test (IAT) and the
      NEO Five-Factor Inventory (NEO-FFI) were applied as measures of extraversion
      which were not correlated in our sample. IAT extraversion was negatively
      correlated with automatic reactivity of the caudate head, thalamus, and inferior
      frontal cortex to sad faces. NEO-FFI extraversion was negatively correlated with
      response of the inferior frontal cortex and putamen to sad faces. For masked
      happy faces, an inverse correlation of the IAT effect for extraversion with
      activation of the caudate head and superior parietal lobule was observed. NEO-FFI
      extraversion was inversely correlated with the response of the thalamus to happy
      faces. Neither NEO-FFI extraversion nor IAT effect were significantly related to
      brain response to masked neutral faces (compared to the no face condition). Taken
      together, a specific heightened responsivity of the fronto-striatal-thalamic
      circuit to facial emotions which are arousing stimuli might underlie introverts'
      preference for avoiding social interactions. Research on the neurobiology of
      extraversion could benefit from the application of implicit in addition to
      explicit measurement instruments when automatic neural responses are
      investigated.

PMID- 20144696
TI  - Brain cellular localization of endothelin receptors A and B in a rodent model of
      diffuse traumatic brain injury.
AB  - Endothelin-1 exerts potent vasoconstrictor and vasodilatory effects through its
      actions on its receptors A (ETrA) and B (ETrB), respectively. While ETrA and B
      have classically been thought to be expressed on vascular cell types, more recent
      evidence suggests that, particularly following brain injury, their expression may
      be seen in other, non-vascular cell types. To date no studies have
      comprehensively studied the cellular location of endothelin receptors following
      traumatic brain injury (TBI). Therefore, this study investigates the cellular
      localization of ETrA and B in normal and traumatized brains using an impact
      acceleration device. Adult male Sprague-Dawley rats were subjected to TBI by
      weight drop (450 g) from either 1.5, a distance known to elicit mild TBI in the
      absence of changed in cerebral blood flow (CBF) or 2 m, a distance shown to cause
      a significant reduction in CBF. One set of impacted brains were processed for
      Western determination of ETrA and B expression. Another set were processed for
      immunofluorescence (IF). For IF, ETrA and ETrB antibodies were combined with cell
      markers for neurons, astrocytes, microglia, oligodendrocytes, smooth muscle cells
      and endothelial cells of blood vessels. While ETrA and B was upregulated after
      more moderate to severe injury (2 m) overall receptor expression was unchanged in
      response to mild trauma (1.5 m). Double labeling IF confirmed prominent ETrA and
      ETrB labeling in NeuN labeled pyramidal neurons and interneurons in sensorymotor
      cortex (smCx) and hippocampus (hipp) post TBI. ETrA rather than ETrB was
      preferentially co-localized in vascular smooth muscle cells. After injury, a
      subpopulation of astrocytes in white matter co-localized ETrA but not ETrB.
      Localization of either receptor in endothelial cells was sparse. No prominent IF
      was detected in microglia and oligodendrocytes. Taken together with previous
      findings in other pathological states that show an apparent shift in the
      localization of ETrA and B, the observed receptor shifts in this work may
      underlie the ET-1-mediated pathotrajectory of TBI including hypoperfusion.

PMID- 20144697
TI  - Role for ionic fluxes on cell death and apoptotic volume decrease in cultured
      cerebellar granule neurons.
AB  - Recent evidence suggests a major role for ionic fluxes in apoptotic cell death
      and apoptotic volume decrease. Cerebellar granule neurons (CGN) undergo apoptosis
      when they are treated with staurosporine or camptothecin (CPT) or when cells are
      transferred from high extracellular potassium (25 mM KCl [K(+)](e), K25) to low
      potassium concentration (5 mM KCl [K(+)](e), K5). In this study we described that
      all three apoptotic conditions induced apoptotic volume decrease in CGN and that
      two different potassium channel blockers, cesium (Cs(+)) and tetraethylammonium
      (TEA(+)), prevented the apoptotic volume decrease, caspase-3 activation, nuclear
      condensation and cell death induced by K5 and CPT, but not by staurosporine.
      Cs(+) and TEA(+) also blocked membrane currents generated in K5 conditions in
      CGN. On the other hand, non specific Cl(-) channel blockers such as 4,4'
      diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) prevented loss of cell
      volume induced by K5 or staurosporine. Only the Cl(-) channels blocker but not
      the K(+) channels blockers protected from staurosporine-induced death of CGN.
      These data suggest that ionic fluxes play a key role in the activation of the
      apoptotic volume decrease and apoptotic death of CGN, but the fine mechanism
      seems to depend on the apoptotic condition.

PMID- 20144698
TI  - Bisphenol A may cause testosterone reduction by adversely affecting both testis
      and pituitary systems similar to estradiol.
AB  - Bisphenol A (BPA) causes reproductive toxicities, but the mechanisms are still
      unclear. In the present study, we sought to clarify these mechanisms in
      comparison with those of 17beta-estradiol (E2). Prepubertal Wistar/ST male rats
      (4 weeks old) were subcutaneously administered BPA (0, 20, 100 and 200 mg/kg/day)
      or E2 (10 and 100 microg/kg/day) for 6 weeks. Both BPA and E2 treatments
      decreased plasma and testicular testosterone levels, and plasma luteinizing
      hormone (LH), but not E2 and follicle-stimulating hormone levels, though E2
      treatment increased its plasma level. In relation to the decreased testosterone
      levels, BPA and E2 decreased expressions of steroidogenic enzymes and cholesterol
      carrier protein in Leydig cells. Thus, decreased testosterone levels in plasma
      might have resulted from decreased expressions of these enzymes and protein as
      well as from decreased plasma LH levels. Interestingly, the changes in
      steroidogenic enzymes and carrier protein were observed at lower levels of
      exposure to BPA or E2 than those inhibiting plasma LH levels. Microscopically,
      200 mg/kg BPA and 100 microg/kg E2 significantly decreased Leydig cell numbers in
      the testis. In addition, BPA and E2 also decreased expression of estrogen
      receptor alpha-mRNA, which might be related to the decreased numbers of Leydig
      cells. Thus, BPA directly affects not only the Leydig cells but also the
      pituitary gland, but the former may be impaired at lower exposure concentrations
      than the latter.

PMID- 20144699
TI  - Sensitivity of psychophysical measures to signal processor modifications in
      cochlear implant users.
AB  - Experienced users of the Clarion cochlear implant were tested acutely with the
      HiResolution (HiRes) and HiRes Fidelity120 (F120) processing strategies. Three
      psychophysically-based tests were used including spectral-ripple discrimination,
      Schroeder-phase discrimination and temporal modulation detection. Three clinical
      outcome measures were used including consonant-nucleus-consonant (CNC) word
      recognition in quiet, word recognition in noise and the clinical assessment of
      music perception (CAMP). Listener's spectral-ripple discrimination ability
      improved with F120, but Schroeder-phase discrimination was worse with F120 than
      with HiRes. Listeners who had better than average acuity showed the biggest
      effects. There were no significant effects of the processing strategy on any of
      the clinical abilities nor on temporal modulation detection. Additionally, the
      listeners' day-to-day clinical strategy did not appear to influence the result
      suggesting that experience with the strategies did not play a significant role.
      The results underscore the value of acoustic psychophysical measures through the
      sound processor as a tool in clinical research, because these measures are more
      sensitive to changes in the processing strategies than traditional clinical
      measures, e.g. speech understanding. The measures allow for the evaluation of
      sensitivity to specific acoustic attributes revealing the extent to which
      different processing strategies affect these basic abilities and could thus
      improve the efficiency of the development of processing strategies.

PMID- 20144700
TI  - Detection of sinusoidal amplitude modulation in logarithmic frequency sweeps
      across wide regions of the spectrum.
AB  - Many natural sounds such as speech contain concurrent amplitude and frequency
      modulation (AM and FM), with the FM components often in the form of directional
      frequency sweeps or glides. Most studies of modulation coding, however, have
      employed one modulation type in stationary carriers, and in cases where mixed
      modulation sounds have been used, the FM component has typically been confined to
      an extremely narrow range within a critical band. The current study examined the
      ability to detect AM signals carried by broad logarithmic frequency sweeps using
      a 2-alternative forced-choice adaptive psychophysical design. AM-detection
      thresholds were measured as a function of signal modulation rate and carrier
      sweep frequency region. Thresholds for detection of AM in a sweep carrier ranged
      from -8 dB for an AM rate of 8 Hz to -30 dB at 128 Hz. Compared to thresholds
      obtained for stationary carriers (pure tones and filtered Gaussian noise),
      detection of AM carried by frequency sweeps substantially declined at low (12 dB
      at 8 Hz) but not high modulation rates. Several trends in the data, including
      sweep- versus stationary-carrier threshold patterns and effects of frequency
      region were predicted from a modulation filterbank model with an envelope
      correlation decision statistic.

PMID- 20144702
TI  - Effects of a bupivacaine nerve block on the axonal transport of Tumor Necrosis
      Factor-alpha (TNF-alpha) in a rat model of carrageenan-induced inflammation.
AB  - Many pro-inflammatory cytokines are involved in the process of inflammatory pain.
      Bi directional axonal transport of Tumor Necrosis Factor-alpha (TNF-alpha) occurs
      in case of neuropathic pain induced by nerve ligation. We used an in vivo
      preparation with injection of carrageenan and fluorescent TNF-alpha in the
      territory of the saphenous nerve of rats to study this transport. We have shown
      that retrograde transport of TNF-alpha occurs after an inflammatory insult caused
      by the injection of carrageenan. This transport was likely mediated by the TNF
      receptor 1. A nerve block with bupivacaine totally abolishes the expression of
      the receptor in the dorsal root ganglion and the retrograde transport of TNF
      alpha. In addition, bupivacaine at low concentrations (1-10 microM) was able to
      stop the axonal transport ex vivo. Tetrodotoxin was less efficacious for
      inhibiting the TNF-alpha transport and the rise in receptor expression and for
      inhibiting the axonal transport ex vivo. This may partly explain the efficacy of
      nerve blocks with bupivacaine to decrease the neurogenic inflammation and in a
      lower extent the long-term inhibition of hyperalgesic phenomenon observed in
      animals and in humans.

PMID- 20144701
TI  - Presbycusis phenotypes form a heterogeneous continuum when ordered by degree and
      configuration of hearing loss.
AB  - Many reports have documented age-by-frequency increases in average auditory
      thresholds in various human populations. Despite this, the prevalence of
      different patterns of hearing loss in presbycusis remains uncertain. We examined
      'presbycusis phenotypes' in a database of 960 subjects (552 female, 408 male, 18
      92 years) that each had 30 measures of peripheral hearing sensitivity: pure tone
      audiograms for left and right ears from 0.25 to 8 kHz and DPOAE for each ear with
      F(mean)=1-6.4 kHz. Surprisingly, the hearing phenotypes did not naturally
      separate into discrete classes of presbycusis. Principal component (PC) analysis
      revealed that two principal components account for 74% of the variance among the
      30 measures of hearing. The two components represent the overall degree (PC1) and
      configuration of loss (Flat vs. Sloping; PC2) and the phenotypes form a continuum
      when plotted against them. A heuristic partitioning of this continuum produced
      classes of presbycusis that vary in their degree of Sloping or Flat hearing loss,
      suggesting that the previously reported sub-types of presbycusis arise from the
      categorical segregation of a continuous and heterogeneous distribution. Further,
      most phenotypes lie intermediate to the extremes of either Flat or Sloping loss,
      indicating that if audiometric configuration does predict presbycusis etiology,
      then a mixed origin is the most prevalent.

PMID- 20144703
TI  - Improved methodology for identifying the teratogenic potential in early drug
      development of hERG channel blocking drugs.
AB  - Drugs blocking the potassium current IKr of the heart (via hERG channel
      inhibition) have the potential to cause hypoxia-related teratogenic effects.
      However, this activity may be missed in conventional teratology studies because
      repeat dosing may cause resorptions. The aim of the present study was to
      investigate an alternative protocol to reveal the teratogenic potential of IKr
      blocking drugs. The IKr blocker astemizole, given as a single dose (80 mg/kg) on
      gestation day (GD) 13 to pregnant rats caused digital defects. In whole rat
      embryo culture (2h) on GD 13, astemizole caused a decrease in embryonic heart
      rate at 20 nM, and arrhythmias at 200-400 nM. Cetirizine, without IKr-blocking
      properties, did not affect the rat embryonic heart in vitro. The present study
      shows that single dose testing on sensitive days of development, together with
      whole embryo culture, can be a useful methodology to better characterize the
      teratogenic potential of IKr-blocking drugs.

PMID- 20144704
TI  - Suppression of mutagenesis by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (7,8
      dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate) by human MTH1, MTH2, and NUDT5.
AB  - To assess the functions of the three human MutT-type enzymes, MTH1, MTH2, and
      NUDT5, mutation induction by an oxidized form of dGTP, 8-hydroxy-2'
      deoxyguanosine 5'-triphosphate (8-OH-dGTP; 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'
      triphosphate), was examined using human 293T cells treated with their specific
      siRNAs. Shuttle plasmid DNA containing the supF gene was first transfected into
      the cells, and then 8-OH-dGTP was introduced by means of osmotic pressure.
      Escherichia coli cells were transformed with the DNAs replicated in the treated
      cells. The knockdown of the MTH1, MTH2, and NUDT5 proteins increased the A:T -->
      C:G substitution mutations induced by 8-OH-dGTP. In addition, the increase in the
      induced mutation frequency was more evident in the triple-knockdown cells. These
      results indicate that all three of the human MTH1, MTH2, and NUDT5 proteins act
      as a defense against the mutagenesis induced by oxidized dGTP.

PMID- 20144705
TI  - Thiol-sensitive mutant forms of human SOD2, L60F, and I58T: the role of Cys140.
AB  - We previously described a coding mutation (L60F) in the mitochondrial superoxide
      dismutase (SOD2) gene of the human T cell leukemia-derived cell line Jurkat. In
      cell extracts the L60F mutant enzyme showed unusual inhibition by thiol reagents
      not seen in wild-type enzyme. Here we compare the properties of purified
      recombinant L60F SOD2 with a previously described SOD2 mutant, I58T. Both mutant
      proteins display a weakened dimer-dimer interaction and thermal instability at 55
      degrees C. Both I58T and L60F lose activity at 37 degrees C in the presence of 5
      mM N-ethylmaleimide, whereas the wild-type SOD2 does not. Each subunit contains
      one exposed, reactive cysteine residue at position 196 and a second cysteine
      residue at 140, which is buried and unreactive in the wild-type tetramer. We
      propose that the mutant enzymes, which exist largely as dimers, allow both
      cysteine residues to react with thiol reagents. When the cysteine residue at 140
      was changed to serine by site-directed mutagenesis, both double mutants
      I58T/C140S and L60F/C140S lost their increased thiol sensitivity. The
      evolutionary significance of Cys140 is discussed.

PMID- 20144706
TI  - Characterization of indigenous Rhodococcus sp. 602, a strain able to accumulate
      triacylglycerides from naphthyl compounds under nitrogen-starved conditions.
AB  - An indigenous bacterium (strain 602) isolated in this study from a polluted soil
      sample collected in Patagonia (Argentina) was investigated in relation to its
      metabolic responses under unbalanced growth conditions. This strain was
      identified as Rhodococcus sp. by molecular analyses. Strain 602 showed the
      ability to degrade a wide range of compounds and to synthesize triacylglycerols
      under nitrogen-limiting conditions. Cells were also able to accumulate
      triacylglycerols during cultivation on naphthalene and naphthyl-1-dodecanoate.
      Triacylglycerols produced by resting cells in the presence of naphthyl-1
      dodecanoate contained only short-chain length fatty acids (from C(8) to C(12)),
      suggesting an initial attack of the substrate by an esterase releasing 1-naphthol
      and dodecanoic acid, which was subsequently degraded by beta-oxidation. On the
      other hand, naphthalene seemed to be degraded by a mono-oxygenase yielding 1
      naphthol, which was then transformed to 4-hydroxy-1-tetralone and to other
      possible metabolic intermediates. On the basis of the results obtained, a pathway
      involved in the metabolism of both aromatic compounds under nitrogen starvation
      by strain 602 is proposed. The results also demonstrated that Rhodococcus sp. 602
      maintains its metabolic activity even in the absence of a nitrogen source.
      Intracellular triacylglycerols may help cells to maintain their catabolic
      activities under these growth-restricting conditions.

PMID- 20144707
TI  - Phylogenetic diversity of archaeal 16S rRNA and ammonia monooxygenase genes from
      tropical estuarine sediments on the central west coast of India.
AB  - Phylogenetic diversity analyses of archaeal 16S rRNA and ammonia monooxygenase
      subunit A (AamoA) genes were carried out on sediment samples from the Mandovi and
      Zuari estuaries on the central west coast of India. The 16S rRNA gene libraries
      revealed quite high diversity of archaea in these sediments compared to previous
      reports from tropical and temperate estuarine sediments. Uncultured members of
      Crenarchaeota accounted for approximately 78% of 433 archaeal 16S rRNA gene
      clones from both of the estuaries. We detected archaeal 16S and amoA gene-related
      organisms capable of ammonia oxidation. Among Crenarchaeota, marine group I (MG
      I) was the most predominant. Clones matching the uncultured methanobacteria were
      predominant among the ribogroups of Euryarchaeota. Our results indicate that
      archaeal diversity in tropical estuarine sediments is influenced by the mangrove
      vegetation bordering the lower stretches of both estuaries. Higher diversity may
      be related to elevated land drainage during the monsoon, particularly in the
      Mandovi estuary sediments. Also, the diversity of AamoA sequences was higher in
      Mandovi sediments than those from Zuari and other tropical and/or temperate
      estuaries studied previously.

PMID- 20144709
TI  - In situ measurement of spectral changes in the anterior eye following application
      of ultraviolet-absorbing compounds.
AB  - The ocular structures are very sensitive to damage from ultraviolet (UV)
      radiation, exposure is linked to corneal and conjunctival damage, cataract
      formation and may also be implicated in the aetiology of age-related macular
      degeneration. These structures are usually protected by wearing suitable
      eyeglasses and goggles. An alternative to conventional eyeglasses/goggles is the
      concept of "liquid sunglasses" which involve the topical application of eye drops
      that are designed to block harmful UV radiation reaching the sensitive ocular
      surfaces. The evaluation of such compounds directly applied to the eye surface
      requires in situ measurements to compare the efficacy of different formulations.
      A novel ocular spectrometer system has been used to evaluate changes in the
      transmission of ultraviolet (UV) radiation through the anterior eye following
      topical application of candidate UV-absorbing formulations. The key feature of
      the system is the ability to propagate a beam of light tangentially through the
      anterior eye using a compact, hand-held lens assembly incorporating UV
      transmitting optical fibres. A range of formulations containing UV-absorbing
      compounds were topically applied to ex vivo rabbit eyes. Significant increases in
      the absorption of the UV spectrum were detected in seven of the eight
      formulations studied, demonstrating the potential of this measurement technique
      in the evaluation of formulations developed as potential topical ocular
      sunscreens.

PMID- 20144710
TI  - Influence of the introduction of a solubility enhancer on the formulation of
      lipidic nanoparticles with improved drug loading rates.
AB  - The objective of the present paper is to develop lipidic nanoparticles (NP) able
      to encapsulate drugs presenting limited solubility in both water and lipids, with
      high loading rates, and without using organic solvents. In this goal, a
      solubility enhancer, a macrogolglyceride (Labrasol), was incorporated in a
      formulation process based on a low-energy phase inversion temperature method.
      From electrical conductivity through the temperature scans, it appears that
      presence of Labrasol does not prevent the phase inversion, and it takes part in
      the microemulsion structuring, probably of bicontinuous type. After screening
      pseudo-ternary diagrams, the feasibility of NP was established. From results of a
      partial least square analysis, it appears that these NP present a core-shell
      structure where Labrasol is well encapsulated and contributes to the formation of
      the oily liquid core of the NP. The diameter of the NP, assessed by dynamic light
      scattering, remains kinetically stable. These NP, smaller than 200 nm, spherical
      in shape as attested by cryo-transmission electron micrographs, are able to
      encapsulate a tripentone, a new anticancer agent, with drug loading rates up to
      6.5% (w/w). So highly drug-loaded lipidic nanocarriers were developed without
      using the slightest organic solvent trace, and making it easily possible dose
      adjustment.

PMID- 20144708
TI  - The sodium pump and cardiotonic steroids-induced signal transduction protein
      kinases and calcium-signaling microdomain in regulation of transporter
      trafficking.
AB  - The Na/K-ATPase was discovered as an energy transducing ion pump. A major
      difference between the Na/K-ATPase and other P-type ATPases is its ability to
      bind a group of chemicals called cardiotonic steroids (CTS). The plant-derived
      CTS such as digoxin are valuable drugs for the management of cardiac diseases,
      whereas ouabain and marinobufagenin (MBG) have been identified as a new class of
      endogenous hormones. Recent studies have demonstrated that the endogenous CTS are
      important regulators of renal Na(+) excretion and blood pressure. The Na/K-ATPase
      is not only an ion pump, but also an important receptor that can transduce the
      ligand-like effect of CTS on intracellular protein kinases and Ca(2+) signaling.
      Significantly, these CTS-provoked signaling events are capable of reducing the
      surface expression of apical NHE3 (Na/H exchanger isoform 3) and basolateral Na/K
      ATPase in renal proximal tubular cells. These findings suggest that endogenous
      CTS may play an important role in regulation of tubular Na(+) excretion under
      physiological conditions; conversely, a defect at either the receptor level (Na/K
      ATPase) or receptor-effector coupling would reduce the ability of renal proximal
      tubular cells to excrete Na(+), thus culminating/resulting in salt-sensitive
      hypertension.

PMID- 20144711
TI  - Controlled release of metronidazole benzoate from poly epsilon-caprolactone
      electrospun nanofibers for periodontal diseases.
AB  - Poly epsilon-caprolactone (PCL) nanofibers containing metronidazole benzoate
      (MET) were successfully electrospun and evaluated for periodontal diseases.
      Solutions of 10.5% w/v PCL and 5-15%w/w MET in mixtures of dichloromethane
      (DCM)/N,N-dimethylformamide (DMF) with ratios of 90:10, 80:20 and 70:30 v/v were
      prepared, and the nanofibers were produced by electrospinning technique. Scanning
      electron microscopy (SEM) was used to investigate the morphology and average
      diameter of the electrospun nanofibers. DSC results indicated a molecular
      dispersion of MET in the PCL nanofibers and showed a decrease in crystallinity of
      PCL nanofibers by adding MET. Results showed that an increase in the DCM:DMF
      ratio led to a decrease in the solution conductivity and an increase in the
      solution viscosity as well as in the nanofibers diameter. Also increasing
      metronidazole benzoate concentration caused an increase in the solution
      conductivity and a decrease in the solution viscosity as well as in the
      nanofibers diameter. In vitro drug release studies in phosphate buffer solution
      (pH 7.4) showed that the drug release rate was affected by the solvents ratio and
      the drug concentration. Moreover, the burst release was low, and sustained drug
      release was prolonged to at least 19 days.

PMID- 20144712
TI  - Tissue section AFM: In situ ultrastructural imaging of native biomolecules.
AB  - Conventional approaches for ultrastructural high-resolution imaging of biological
      specimens induce profound changes in bio-molecular structures. By combining
      tissue cryo-sectioning with non-destructive atomic force microscopy (AFM) imaging
      we have developed a methodology that may be applied by the non-specialist to both
      preserve and visualize bio-molecular structures (in particular extracellular
      matrix assemblies) in situ. This tissue section AFM technique is capable of: i)
      resolving nm-microm scale features of intra- and extracellular structures in
      tissue cryo-sections; ii) imaging the same tissue region before and after
      experimental interventions; iii) combining ultrastructural imaging with
      complimentary microscopical and micromechanical methods. Here, we employ this
      technique to: i) visualize the macro-molecular structures of unstained and
      unfixed fibrillar collagens (in skin, cartilage and intervertebral disc), elastic
      fibres (in aorta and lung), desmosomes (in nasal epithelium) and mitochondria (in
      heart); ii) quantify the ultrastructural effects of sequential collagenase
      digestion on a single elastic fibre; iii) correlate optical (auto fluorescent)
      with ultrastructural (AFM) images of aortic elastic lamellae.

PMID- 20144713
TI  - CYP24A1-deficient mice as a tool to uncover a biological activity for vitamin D
      metabolites hydroxylated at position 24.
AB  - The CYP24A1 enzyme (25-hydroxyvitamin D-24-hydroxylase) not only is involved in
      the catabolic breakdown of 1,25-dihydroxyvitamin D [1,25(OH)2D] but also
      generates the 24,25-dihydroxyvitamin D [24,25(OH)2D] metabolite. The biological
      activity of 24,25(OH)2D remains controversial. While in vitro studies suggest
      that primary cultures of rat rib chondrocytes respond to 24,25(OH)2D in a
      maturation-specific manner and that the metabolite is necessary for the cells to
      progress from a proliferating, immature status to a differentiated, 1,25(OH)2D
      responsive stage, in vivo evidence to support this putative role remains lacking.
      Studies in chicken showed increases in serum levels of 24,25(OH)2D and of the
      renal mRNA levels of Cyp24a1 following fracture, suggesting a role for
      24,25(OH)2D in fracture repair. The Cyp24a1-deficient mouse strain represents an
      invaluable tool to examine the putative role of 24,25(OH)2D in mammalian fracture
      repair. We have compared fracture repair between Cyp24a1-/- mice and wild-type
      controls. We have observed a delay in the mineralization of the cartilaginous
      matrix of the soft callus in Cyp24a1-/- mutant animals, accompanied by reduced
      expression of chondrocyte marker genes. These results show that Cyp24a1
      deficiency delays fracture repair and strongly suggest that vitamin D metabolites
      hydroxylated at position 24, such as 24,25(OH)2D3, play an important role in the
      mechanisms leading to normal fracture healing.

PMID- 20144714
TI  - Measurement of sex steroids in murine blood and reproductive tissues by liquid
      chromatography-tandem mass spectrometry.
AB  - Accurate measurement of sex steroids is essential to evaluate mouse models for
      human reproductive development and disorders. The recent advent of liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) assays that match the
      sensitivity of steroid immunoassay could overcome problems arising from the
      limited specificity of steroid immunoassay. In this current study we validate a
      LC-MS/MS assay for the measurement of key sex steroids from murine serum and
      reproductive tissues. The assay gave excellent dilutional linearity (r(2)> or
      =0.98) and reproducibility (CV< or =10% of replicate samples) in serum and
      reproductive tissues with sensitive quantitation limits; testosterone (T; 2pg),
      dihydrotestosterone (DHT; 10pg), 5alpha-androstane-3alpha,17beta-diol
      (3alphaDiol; 40pg), 5alpha-androstane-3beta,17beta-diol (3betaDiol; 40pg),
      estradiol (E2; 0.5pg) and estrone (E1; 0.3pg). Using 0.1mL sample, T was the only
      consistently detectable steroid (detection limit 20pg/ml) in both male and female
      mouse serum. In the testis, T and DHT were quantifiable as were both diols at
      relatively high levels. Prostatic T levels were low and DHT was determined to be
      the most abundant androgen in this tissue. Uterine and ovarian levels of E2, E1
      and T were measurable, with levels varying according to estrous cycle stage.
      Hence, we demonstrate that this LC-MS/MS method has the sensitivity, specificity
      and multi-analyte capability to offer accurate steroid profiling in mouse serum
      and reproductive tissues.

PMID- 20144715
TI  - Genes encoding proteins with peritrophin A-type chitin-binding domains in
      Tribolium castaneum are grouped into three distinct families based on phylogeny,
      expression and function.
AB  - This study is focused on the characterization and expression of genes in the red
      flour beetle, Tribolium castaneum, encoding proteins that possess one or more six
      cysteine-containing chitin-binding domains related to the peritrophin A domain
      (ChtBD2). An exhaustive bioinformatics search of the genome of T. castaneum
      queried with ChtBD2 sequences yielded 13 previously characterized chitin
      metabolic enzymes and 29 additional proteins with signal peptides as well as one
      to 14 ChtBD2s. Using phylogenetic analyses, these additional 29 proteins were
      classified into three large families. The first family includes 11 proteins
      closely related to the peritrophins, each containing one to 14 ChtBD2s. These are
      midgut-specific and are expressed only during feeding stages. We propose the name
      "Peritrophic Matrix Proteins" (PMP) for this family. The second family contains
      eight proteins encoded by seven genes (one gene codes for 2 splice variants),
      which are closely related to gasp/obstructor-like proteins that contain 3 ChtBD2s
      each. The third family has ten proteins that are of diverse sizes and sequences
      with only one ChtBD2 each. The genes of the second and third families are
      expressed in non-midgut tissues throughout all stages of development. We propose
      the names "Cuticular Proteins Analogous to Peritophins 3" (CPAP3) for the second
      family that has three ChtBD2s and "Cuticular Proteins Analogous to Peritophins 1
      (CPAP1) for the third family that has 1 ChtBD2. Even though proteins of both
      CPAP1 and CPAP3 families have the "peritrophin A" domain, they are expressed only
      in cuticle-forming tissues. We determined the exon-intron organization of the
      genes, encoding these 29 proteins as well as the domain organization of the
      encoded proteins with ChtBD2s. All 29 proteins have predicted cleavable signal
      peptides and ChtBD2s, suggesting that they interact with chitin in extracellular
      locations. Comparison of ChtBD2s-containing proteins in different insect species
      belonging to different orders suggests that ChtBD2s are ancient protein domains
      whose affinity for chitin in extracellular matrices has been exploited many times
      for a range of biological functions. The differences in the expression profiles
      of PMPs and CPAPs indicate that even though they share the peritrophin A motif
      for chitin binding, these three families of proteins have quite distinct
      biological functions.

PMID- 20144716
TI  - Regulation of axonal trafficking of cytochrome c oxidase IV mRNA.
AB  - Trafficking and local translation of axonal mRNAs play a critical role in the
      development and function of this neuronal subcellular structural domain. In this
      report, we studied cytochrome c oxidase subunit IV (COXIV) mRNA trafficking into
      distal axons of primary superior cervical ganglia (SCG) neurons, and provided
      evidence that axonal trafficking and mitochondrial association of the mRNA are
      mediated by an element located in a 38bp-long, hairpin-loop forming region within
      the 3'UTR of the transcript. Our results also suggest that suppression of local
      translation of COXIV mRNA results in significant attenuation of axonal
      elongation. Taken together, the results provide the first evidence for the
      existence of a cis-acting axonal transport element within a nuclear-encoding
      mitochondrial gene, and demonstrate the importance of the axonal trafficking and
      local translation of nuclear-encoded mitochondrial mRNAs in axonal growth.

PMID- 20144717
TI  - Expression of N-terminally truncated forms of rat peroxiredoxin-4 in insect
      cells.
AB  - Peroxiredoxins (Prxs), a family of thioredoxin-dependent peroxidases, are highly
      conserved in many organisms and function in detoxifying reactive oxygen species
      as well as other cellular processes. Six members of the Prx family are known in
      mammals, i.e., Prx-1 through -6. Among these proteins, only Prx-4 appears to
      contain a signal peptide that serves for localization in the endoplasmic
      reticulum, membrane translocation and secretion into the extracellular space, as
      demonstrated in a previous study using a baculovirus-insect cell system. The
      present study was conducted to determine whether the signal peptide-truncated
      mutant of rat Prx-4 is expressed as an enzymatically active form and is produced
      in large amounts. Two N-terminally truncated mutants were prepared by deletion of
      only the signal peptide and the larger region encompassing both the signal and
      the unique extension to Prx-4. These mutants were successfully produced within
      Spodoptera frugiperda 21 cells by infection with the recombinant baculoviruses,
      rather than by extracellular secretion. Both mutants were efficiently purified to
      homogeneity by two column chromatography steps. Biochemical characterization of
      the purified proteins showed that the truncated enzymes are enzymatically active
      and form an oligomeric structure, as reported for the mammalian Prx family. The
      findings also suggest that the unique extension plays a role in the regulation of
      non-covalent oligomerization. More than 4 mg of the purified proteins can be
      obtained from cells grown in monolayer cultures in twenty 75 cm(2) tissue culture
      flasks. The procedures described in this study permit recombinant Prx-4 to be
      prepared more efficiently and easily for purposes of crystallization and antibody
      preparation.

PMID- 20144719
TI  - Isolation of seven IL-17 family genes from the Japanese pufferfish Takifugu
      rubripes.
AB  - In humans, the IL-17 family is composed of six members (A-F). The A, E and F
      forms have been extensively studied in numerous mammalian species. However, there
      are few reports regarding IL-17 expression in teleost. In this study, IL-17
      family genes were isolated from the Japanese pufferfish (Fugu) and their
      structure and expression profile were analyzed. Screening of the Fugu genome
      database revealed the existence of five scaffolds containing IL-17 family
      homologous genes. Scaffold_1 contained three IL-17 family homologues including IL
      17A/F1, 2 and C2, and IL-17A/F1 and two located in tandem. This was similar to
      the IL-17A/F1 and two genes in zebrafish and to human IL-17A and F. Other
      scaffolds 38, 143 and 430, contained IL-17 family homologous genes that were
      identical to IL-17D, A/F3 and C1 in Fugu, respectively. Moreover, IL-17 family
      homologues on scaffold_264 included a novel type of IL-17 family genes in
      teleost. These isolates contained four cysteine residues that were involved in
      the formation of a typical cysteine knot consisting of two disulphide linkages.
      However, IL-17A/F2 did not demonstrate any conservation at the second and fourth
      cysteine residues. The tissue distribution of the Fugu IL-17 family genes was
      also found to differ. In particular, IL-17 family genes were highly expressed in
      the head kidney and gill. Moreover, expression of IL-17 family genes was
      significantly up-regulated in the lipopolysaccharide-stimulated head kidney.
      These results suggested that Fugu IL-17 family members were involved in
      inflammatory responses.

PMID- 20144720
TI  - Prognostic factor and quality of life analysis in 160 patients aged > or =60
      years with hematologic neoplasias treated with allogeneic hematopoietic cell
      transplantation.
AB  - Toxicity-reduced conditioning is a curative treatment option for medically
      compromised or elderly patients ineligible for myeloablative hematopoietic cell
      transplantation (HCT). The aim of this study was to detect prognostic factors for
      overall survival (OS) and to evaluate quality of life (QOL) in a large
      homogeneous cohort of 160 consecutive patients aged > or =60 years treated with
      allogeneic HCT. We evaluated age, sex, performance status, comorbidities,
      pulmonary function, lactic dehydrogenase concentration, type of donor, disease
      status, CD34(+) cells transplanted, cytomegalovirus status, time from diagnosis
      to HCT, and the development of acute and chronic graft-versus-host disease
      (GVHD). All patients who survived for > or =6 months (n = 79) were asked to
      complete a QOL survey. All patients (median age, 64.7 years; range, 60.1-76
      years) received pretransplantation conditioning with fludarabine, BCNU, and
      melphalan. With a median follow-up of 35 months, the 1-year OS was 62.4% and 3
      year OS was 47.4%. Multivariate analysis revealed compromised performance status
      as the most significant negative prognostic parameter for OS (P < .003), whereas
      male donor (P = .008) and chronic GVHD (P = .024) were associated with better OS.
      The 89% of survivors who returned the QOL questionnaire rated their global QOL as
      good-to-excellent despite impaired functional capabilities and such symptoms as
      fatigue, dyspnea, and loss of appetite. The main prognostic factor was
      performance status, not age. Our data suggest that toxicity-reduced conditioning
      offers a chance for enhanced OS with an adequate QOL.

PMID- 20144718
TI  - Critical interactions in the stability control region of tropomyosin.
AB  - Our laboratory has recently described a stability control region in the two
      stranded alpha-helical coiled-coil alpha-tropomyosin that accounts for overall
      protein stability but is not required for folding (Hodges et al., 2009). We have
      used a synthetic peptide approach to investigate three stability control sites
      within the stability control region (residues 97-118). Two of the sites,
      electrostatic cluster 1 (97-104, EELDRAQE) and electrostatic cluster 2 (112-118,
      KLEEAEK), feature sequences with unusually high charge density and the potential
      to form multiple intrachain and interchain salt bridges (ionic attractions). A
      third site (105-111, RLATALQ) features an e position Leu residue, an arrangement
      known previously to enhance coiled-coil stability modestly. A native peptide and
      seven peptide analogs of the tropomyosin sequence 85-119 were prepared by Fmoc
      solid-phase peptide synthesis. Thermal stability measurements by circular
      dichroism (CD) spectroscopy revealed the following T(m) values for the native
      peptide and three key analogs: 52.9 degrees C (Native), 46.0 degrees C (R101A),
      45.3 degrees C (K112A/K118A), and 27.9 degrees C (L110A). The corresponding
      DeltaT(m) values for the analogs, relative to the native peptide, are -6.9
      degrees C, -7.6 degrees C, and -25.0 degrees C, respectively. The dramatic
      contribution to stability made by L110e is three times greater than the
      contribution of either electrostatic cluster 1 or 2, likely resulting from a
      novel hydrophobic interaction not previously observed. These thermal stability
      results were corroborated by temperature profiling analyses using reversed-phase
      high-performance liquid chromatography (RP-HPLC). We believe that the combined
      contributions of the interactions within the three stability control sites are
      responsible for the effect of the stability control region in tropomyosin, with
      the Leu110e contribution being most critical.

PMID- 20144721
TI  - The role of nucleotide sugar transporters in development of eukaryotes.
AB  - The Golgi apparatus membrane of all eukaryotes has nucleotide sugar transporters
      which play essential roles in the glycosylation of glycoproteins, proteoglycans
      and glycolipids. Mutations of these transporters have broad developmental
      phenotypes across many species including diseases in humans and cattle.

PMID- 20144723
TI  - Roles of the catalytic subunit of cAMP-dependent protein kinase A in virulence
      and development of the soilborne plant pathogen Verticillium dahliae.
AB  - Verticillium dahliae is a soilborne fungus that causes vascular wilt disease in a
      broad range of hosts and survives for many years in the soil in the form of
      microsclerotia. Although the role of cAMP-dependent protein kinase A (PKA) has
      been extensively studied in foliar pathogens, there is limited information about
      its role in soilborne fungal pathogens that infect through the root system.
      Genome database search revealed the presence of two PKA catalytic subunit genes
      in V. dahliae, named VdPKAC1 and VdPKAC2. A phylogenetic analysis showed that
      VdPKAC2 groups with fungal PKA catalytic subunits that appear to play a minor
      role in PKA activity. This gene was expressed considerably lower than that of
      VdPKAC1. Although disruption of VdPKAC1 did not affect the ability of V. dahliae
      to infect through the roots of tomato and eggplant, disease severity was
      significantly reduced. Since pathogen-derived ethylene is presumed to play a
      major role in symptom induction in vascular wilt diseases, ethylene generation
      was measured in fungal culture. The mutants defective in VdPKAC1 produced less
      ethylene than the corresponding wild type strains, suggesting a regulatory role
      of PKA in ethylene biosynthesis. Growth rates of these mutants were similar to
      those of wild type strains, while the rate of spore germination was slightly
      elevated and conidia production was significantly reduced. When grown on minimal
      media, the mutants showed greater microsclerotia production compared with the
      wild type strains. These results suggest multiple roles of VdPKAC1, including
      virulence, conidiation, microsclerotia formation, and ethylene biosynthesis, in
      the soilborne fungus V. dahliae.

PMID- 20144722
TI  - The role of mucin-type O-glycans in eukaryotic development.
AB  - Newly emerging genetic studies have revealed that a subset of the family of
      glycosyltransferases responsible for the formation of mucin-type O glycans is
      essential for normal development. As additional genetic, biochemical and physical
      tools are developed to interrogate the complex structure and surface location of
      this under-studied class of carbohydrate, no doubt additional roles will be
      elucidated.

PMID- 20144724
TI  - Fungal network responses to grazing.
AB  - Mycelial networks operate on scales from microscopic to many m(2) and naturally
      persist for extended periods. As fungi exhibit highly adaptive development, it is
      important to test behavioural responses on natural substrata with realistic
      nutrient levels across a range of spatial scales and extended time periods. Here
      we quantified network responses over 7.5 months in large (57 x 57cm) microcosms
      to test whether grazing shifts the network to a more resilient architecture.
      Resource limitation constrained any ability to respond at all, with both grazed
      and ungrazed networks gradually thinning out over time. Added resources sustained
      further exploratory growth, but only transiently increased cross-connectivity and
      network resilience, when tested by simulated damage in silico. Grazed networks
      were initially weaker and emergence of new exploratory growth was curtailed.
      However, increased interstitial proliferation led to new cross-links,
      consolidating the existing mycelial network and increasing the resilience of the
      network to further attack.

PMID- 20144725
TI  - Characterization of a novel 2,4,6-trichlorophenol-inducible gene encoding
      chlorophenol O-methyltransferase from Trichoderma longibrachiatum responsible for
      the formation of chloroanisoles and detoxification of chlorophenols.
AB  - De novo sequencing of eight internal peptides of purified chlorophenol O
      methyltransferase, or CMT1 (before named as CPOMT), from Trichoderma
      longibrachiatum was performed by MALDI-TOF/TOF and ESI-IT. A novel gene (cmt1)
      encoding CMT1 was cloned by using a PCR approach based on the amino acid sequence
      of two internal peptides. The gene (1637 bp) encoded a protein of 468 amino acids
      with a deduced molecular mass of 52.4 kDa, and a theoretical isoelectric point of
      5.93. This gene contains four introns, whose location was confirmed by comparison
      of cDNA and chromosomal sequences. The expression of cmt1 gene was induced at
      transcriptional level by exposure of fungal mycelia to 2,4,6-trichlorophenol
      (2,4,6-TCP). Putative homologous genes were detected in many different fungal
      strains, including other Trichoderma species. Partial silencing of cmt1 gene
      resulted in a 48.9% (+/-5.2) decrease of CMT1 activity levels in a T.
      longibrachiatum At37 transformant strain by comparison with the wild type,
      whereas a decrease of up to 53.0% was observed in the levels of 2,4,6-TCA
      produced in liquid cultures. Efficient expression of cmt1 gene in Escherichia
      coli unequivocally confirmed that it encodes a CMT1 enzyme.

PMID- 20144726
TI  - Crucial factors of the light perception machinery and their impact on growth and
      cellulase gene transcription in Trichoderma reesei.
AB  - In Trichoderma reesei light stimulates transcription of cellulase genes and this
      regulation has been found to occur, at least in part, through the protein ENVOY.
      Here we analyzed the role of the BLR photoreceptor complex (BLR1/BLR2) in
      photoconidiation and the regulation of gene expression. Both responses were
      dependent on both BLR proteins. Analyses of Deltablr1, Deltablr2 and Deltaenv1
      mutants showed that the BLR proteins regulate growth under illumination. Analysis
      of env1 mutant strains indicated that ENVOY allows the fungus to tolerate
      continuous exposure to light, damped the capacity of Trichoderma to perceive
      changes in light intensity, and suggested that it participates in a negative
      regulatory feedback. Its activity as repressor establishes a period of
      insensitivity to a second light treatment. Interestingly, the stimulation of
      cellulase gene expression by light was also modulated by both blr1 and blr2,
      indicating a key role of the BLR proteins in this pathway.

PMID- 20144727
TI  - Activation of endothelial nitric oxide synthase by the pro-apoptotic drug
      embelin: Striking discrepancy between nitric oxide-mediated cyclic GMP
      accumulation and L-citrulline formation.
AB  - The benzoquinone derivative embelin is a multifunctional drug that not only
      induces apoptosis by inhibiting XIAP, the X chromosome-linked inhibitor of
      apoptosis protein, but also blocks nuclear factor-kappaB signaling pathways,
      thereby leading to down-regulation of a variety of gene products involved in
      tumor cell survival, proliferation, invasion, angiogenesis, and inflammation.
      Here, we report that embelin activates and modulates l-arginine/nitric
      oxide/cyclic GMP signaling in cultured endothelial cells. Embelin elicited a
      rapid increase of intracellular free Ca(2+), leading to activation of endothelial
      nitric oxide synthase (eNOS) and NO-induced cGMP accumulation. While the cGMP
      response was comparable to that caused by other Ca(2+)-mobilizing agents, the
      stimulatory effect of embelin on l-citrulline formation (approximately 4-fold)
      was substantially lower than that observed upon activation of eNOS with the
      Ca(2+) ionophore A23187 (approximately 18-fold), the receptor agonist ATP
      (approximately 16-fold) or the sarco-endoplasmic reticulum Ca(2+)-ATPase
      inhibitor thapsigargin (approximately 14-fold). The apparent discrepancy between
      NO/cGMP and l-citrulline formation in embelin-treated cells was not due to
      enhanced metabolism and/or efflux of l-citrulline, increased NO bioavailability,
      inhibition of cGMP hydrolysis, sensitization of soluble guanylate cyclase (sGC)
      to NO, or enhanced formation of a sGC/eNOS complex. Our puzzling observations
      suggest that embelin improves coupling of endothelial NO synthesis to sGC
      activation through mobilization of an as yet unrecognized signaling pathway.

PMID- 20144728
TI  - Cloning and characterization of an invertebrate type lysozyme from Venerupis
      philippinarum.
AB  - Lysozymes are key proteins to invertebrates in the innate immune responses
      against bacterial infections and providing nutrition as digestion enzymes. In the
      present study, an invertebrate type lysozyme (denoted as VpLYZ) was identified
      from Venerupis philippinarum haemocytes by cDNA library and RACE approaches. The
      full-length cDNA of VpLYZ consisted of 805 nucleotides with a canonical
      polyadenylation signal sequence AATAAA and a polyA tail, and an open-reading
      frame of 558bp encoding a polypeptide of 185 amino acids with a calculated
      molecular mass of 20.87kD and theoretical pI of 8.44. The high similarity of
      VpLYZ with other i-type lysozymes from mollusk indicated that VpLYZ should be a
      new member of i-type lysozyme family. Similar to most i-type lysozymes, VpLYZ
      possessed all conserved features critical for the fundamental structure and
      function of i-type lysozymes, such as three catalytic residues (Glu19, Asn72 and
      Ser75) and i-type specific motif CL(E/L/R/H)C(I/M)C. By semi-quantitative RT-PCR
      analysis, mRNA transcript of VpLYZ was found to be most abundantly expressed in
      the tissues of gills, hepatopancreas and haemocytes, weakly expressed in the
      tissues of muscle, foot and mantle. After clams were challenged by Vibrio
      anguillarum, the mRNA level of VpLYZ in overall haemocyte population was recorded
      by quantitative real-time RT-PCR. VpLYZ mRNA was down-regulated sharply from 6h
      to 12h post-infection. Then, the expression level increased to the peak at 72h
      and recovered to the original level at 96h. All these results indicated that
      VpLYZ was involved in the immune response against microbe infection and
      contributed to the clearance of bacterial pathogens.

PMID- 20144729
TI  - Dietary protein hydrolysates and free amino acids affect the spatial expression
      of peptide transporter PepT1 in the digestive tract of Atlantic cod (Gadus
      morhua).
AB  - The effects of dietary inclusions of size-fractionated peptides and free amino
      acids (FAAs) on Peptide Transporter 1 (PepT1) mRNA levels were assessed along the
      length of the intestine of juvenile Atlantic cod (Gadus morhua). Five groups of
      fish (10-15g) were fed for 46days on diets containing approximately 42% protein,
      provided either as fish meal (FM, control diet) or as a combination of FM with
      whole fish hydrolysate (FH), retenate after ultrafiltration of FH (UFR),
      nanofiltered retenate of FH (NFR), or a mix of FAAs, at a 30% level of FM
      substitution. PepT1 mRNA expression was assessed in pyloric caeca (S1) and the
      remainder of the intestine divided into four equally long segments (S2-S5). PepT1
      transcripts were found in all segments, indicating that the whole intestine is
      involved in peptide absorption. Differences in the regional expression profile of
      PepT1 were found. Under control diet (FM diet) conditions, fish exhibited a
      reduced expression in S5 compared to S2. In fish fed FAA and UFR diets, PepT1
      mRNA levels were higher in S2 and S3 compared to other regions. These data
      suggest that PepT1 may be variably recruited along the whole intestine, including
      the most distal part, in response to changes in the luminal protein source
      content. This adaptive response might be functional to keep a maximal efficiency
      of protein absorption at the intestinal level.

PMID- 20144730
TI  - Metabolic changes in a pyruvate kinase gene deletion mutant of Corynebacterium
      glutamicum ATCC 13032.
AB  - To investigate primary effects of a pyruvate kinase (PYK) defect on glucose
      metabolism in Corynebacterium glutamicum, a pyk-deleted mutant was derived from
      wild-type C. glutamicum ATCC13032 using the double-crossover chromosome
      replacement technique. The mutant was then evaluated under glutamic acid
      producing conditions induced by biotin limitation. The mutant showed an increased
      specific rate of glucose consumption, decreased growth, higher glutamic acid
      production, and aspartic acid formation during the glutamic acid production
      phase. A significant increase in phosphoenolpyruvate (PEP) carboxylase activity
      and a significant decrease in PEP carboxykinase activity occurred in the mutant,
      which suggested an enhanced overall flux of the anaplerotic pathway from PEP to
      oxaloacetic acid in the mutant. The enhanced anaplerotic flux may explain both
      the increased rate of glucose consumption and the higher productivity of glutamic
      acid in the mutant. Since the pyk-complemented strain had similar metabolic
      profiles to the wild-type strain, the observed changes represented intrinsic
      effects of pyk deletion on the physiology of C. glutamicum.

PMID- 20144732
TI  - Higher-order chromatin structure in DSB induction, repair and misrepair.
AB  - Double-strand breaks (DSBs), continuously introduced into DNA by cell metabolism,
      ionizing radiation and some chemicals, are the biologically most deleterious type
      of genome damage, and must be accurately repaired to protect genomic integrity,
      ensure cell survival, and prevent carcinogenesis. Although a huge amount of
      information has been published on the molecular basis and biological significance
      of DSB repair, our understanding of DSB repair and its spatiotemporal arrangement
      is still incomplete. In particular, the role of higher-order chromatin structure
      in DSB induction and repair, movement of DSBs and the mechanism giving rise to
      chromatin exchanges, and many other currently disputed questions are discussed in
      this review. Finally, a model explaining the formation of chromosome
      translocations is proposed.

PMID- 20144731
TI  - MicroRNAs in immune regulation--opportunities for cancer immunotherapy.
AB  - Endogenously produced microRNAs are predicted to regulate the translation of over
      two-thirds all human gene transcripts. Certain microRNAs regulate expression of
      genes that are critically involved in both innate and adaptive immune responses.
      Immune cells represent a highly attractive target for microRNA gene therapy
      approaches, as these cells can be isolated, treated and then reintroduced into
      the patient. In this short review, we discuss how recent discoveries on the roles
      of microRNAs in immune-regulation will advance the field of cancer immunology and
      immunotherapy. Targets identified already in T cells include microRNAs, miR-17-92
      family, miR-155, and miR-181a. In macrophages, miR-125b, miR-146, and miR-155 act
      as Pathogen Associated Molecular Pattern Molecule-associated microRNAs and miR
      34C and miR-214 as Damage Associated Molecular Pattern Molecules-associated miRs.
      We have also demonstrated that the ability of tumors to serve as targets for
      cytolytic effectors is regulated by miR-222 and miR-339.

PMID- 20144733
TI  - Characterization of a novel thrombospondin-related protein in Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite that invades a
      wide range of host cells. The parasite releases a large variety of proteins from
      a secretory organelle, microneme, and the secretion is essential for the parasite
      invasion. We cloned a secreted protein with an altered thrombospondin repeat of
      Toxoplasma gondii (TgSPATR), which was the homologue of Plasmodium SPATRs.
      Immunofluorescence double staining experiment revealed that TgSPATR was co
      localized with a microneme protein, MIC2, and immuno-electron microscopic (IEM)
      analysis detected TgSPATR in the microneme-like structure. TgSPATR secretion was
      induced by ethanol, while an intracellular Ca(2+) chelator, 1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA
      AM), suppressed the ethanol-induced secretion, suggesting the secretion was
      Ca(2+)-dependent, similarly to known microneme proteins. Furthermore, TgSPATR,
      existed on outer surface of the parasites, was detected by incomplete membrane
      permeabilization by saponin and immunofluorescent antibody test (IFAT). Both
      TgSPATR and MIC2 were detected on outer surface of extracellular parasites, but
      not of intracellular single parasites, suggesting they were similarly secreted
      during early stages of parasite invasion. Therefore, TgSPATR is probably new
      member of microneme protein and maybe involved in parasite invasion.

PMID- 20144734
TI  - A network-theoretic approach for decompositional translation across Open
      Biological Ontologies.
AB  - Biological ontologies are now being widely used for annotation, sharing and
      retrieval of the biological data. Many of these ontologies are hosted under the
      umbrella of the Open Biological Ontologies Foundry. In order to support
      interterminology mapping, composite terms in these ontologies need to be
      translated into atomic or primitive terms in other, orthogonal ontologies, for
      example, gluconeogenesis (biological process term) to glucose (chemical ontology
      term). Identifying such decompositional ontology translations is a challenging
      problem. In this paper, we propose a network-theoretic approach based on the
      structure of the integrated OBO relationship graph. We use a network-theoretic
      measure, called the clustering coefficient, to find relevant atomic terms in the
      neighborhood of a composite term. By eliminating the existing GO to ChEBI
      Ontology mappings from OBO, we evaluate whether the proposed approach can re
      identify the corresponding relationships. The results indicate that the network
      structure provides strong cues for decompositional ontology translation and the
      existing relationships can be used to identify new translations.

PMID- 20144735
TI  - Average correlation clustering algorithm (ACCA) for grouping of co-regulated
      genes with similar pattern of variation in their expression values.
AB  - Distance based clustering algorithms can group genes that show similar expression
      values under multiple experimental conditions. They are unable to identify a
      group of genes that have similar pattern of variation in their expression values.
      Previously we developed an algorithm called divisive correlation clustering
      algorithm (DCCA) to tackle this situation, which is based on the concept of
      correlation clustering. But this algorithm may also fail for certain cases. In
      order to overcome these situations, we propose a new clustering algorithm, called
      average correlation clustering algorithm (ACCA), which is able to produce better
      clustering solution than that produced by some others. ACCA is able to find
      groups of genes having more common transcription factors and similar pattern of
      variation in their expression values. Moreover, ACCA is more efficient than DCCA
      with respect to the time of execution. Like DCCA, we use the concept of
      correlation clustering concept introduced by Bansal et al. ACCA uses the
      correlation matrix in such a way that all genes in a cluster have the highest
      average correlation values with the genes in that cluster. We have applied ACCA
      and some well-known conventional methods including DCCA to two artificial and
      nine gene expression datasets, and compared the performance of the algorithms.
      The clustering results of ACCA are found to be more significantly relevant to the
      biological annotations than those of the other methods. Analysis of the results
      show the superiority of ACCA over some others in determining a group of genes
      having more common transcription factors and with similar pattern of variation in
      their expression profiles. Availability of the software: The software has been
      developed using C and Visual Basic languages, and can be executed on the
      Microsoft Windows platforms. The software may be downloaded as a zip file from
      http://www.isical.ac.in/~rajat. Then it needs to be installed. Two word files
      (included in the zip file) need to be consulted before installation and execution
      of the software.

PMID- 20144736
TI  - Abdominal visceral adipose tissue predicts risk of colorectal adenoma in both
      sexes.
AB  - BACKGROUND & AIMS: Small studies have shown inconsistent results regarding the
      association between abdominal visceral adipose tissue and colorectal adenomas. We
      evaluated the effects of visceral adipose tissue volume on the development and
      growth of colorectal adenomas. METHODS: A total of 3922 participants underwent
      colonoscopy and computed tomography from February to November 2008. The
      associations between waist circumference, visceral adipose tissue volume, and
      colorectal adenomas were estimated with adjusted odds ratios and 95% confidence
      intervals (CIs). In addition, the association between characteristics of
      colorectal adenomas and visceral adipose tissue volume was evaluated. RESULTS:
      Compared with participants who had visceral adipose tissue volume of less than
      500 cm(3), the odds ratio for colorectal adenoma was 1.09 (95% CI, 0.87-1.36) for
      a volume of 500 to 999 cm(3), 1.33 (95% CI, 1.04-1.69) for a volume of 1000 to
      1499 cm(3), and 1.43 (95% CI, 1.06-1.94) for a volume of 1500 cm(3) or greater.
      The risk of colorectal adenomas increased with increasing visceral adipose tissue
      volume in both sexes (P trend = .004 in men and .009 in women). Waist
      circumference was associated with colorectal adenomas in men (P trend = .02), but
      not in women. High volume of visceral adipose tissue (>or=1000 cm(3)) had a
      positive association with larger adenomas (>or=10 mm) and multiple adenomas.
      CONCLUSIONS: Abdominal visceral adipose tissue volume can contribute to the
      development and growth of colorectal adenomas, and it was a better predictor for
      risk of colorectal adenomas than body mass index or waist circumference in both
      sexes.

PMID- 20144737
TI  - Electronic images of the month. The hide-bound bowel.

PMID- 20144738
TI  - Tension hemothorax: a dreaded complication of percutaneous liver biopsy.

PMID- 20144740
TI  - Electronic images of the month. Encapsulating peritoneal sclerosis.

PMID- 20144739
TI  - Sildenafil has no effect on portal pressure but lowers arterial pressure in
      patients with compensated cirrhosis.
AB  - BACKGROUND & AIMS: The reduction of portal pressure in patients with early
      compensated cirrhosis may be more responsive to drugs increasing intrahepatic
      vasodilatation than those reducing portal venous inflow. The phosphodiesterase-5
      (PDE-V) inhibitor sildenafil can potentially reduce portal pressure by decreasing
      intrahepatic resistance, but its systemic vasodilatory effects may be
      deleterious. The aim of this study was to evaluate the effect of sildenafil on
      systemic and portal hemodynamics in an open-label pilot study. METHODS: Twelve
      patients with compensated cirrhosis and baseline hepatic venous pressure gradient
      (HVPG) >5 mm Hg received 25 mg of oral sildenafil. Mean arterial pressure (MAP),
      heart rate (HR), and HVPG were repeated after 30 and 60 minutes in 9/12 patients
      at 90 minutes (after an additional 25 mg of sildenafil). HVPG tracings were read
      by 3 blinded observers. RESULTS: All 12 patients were Child A with median MAP of
      92 mm Hg (interquartile range, 83-94) and HVPG 10.4 mm Hg (interquartile range,
      6.6-13.0). While MAP decreased significantly at all time points, sildenafil had
      no effect on HVPG. CONCLUSIONS: As shown with other vasodilators in compensated
      cirrhotic patients, sildenafil at therapeutic doses for erectile dysfunction
      reduces MAP without reducing portal pressure. The search should continue for
      specific intrahepatic vasodilators.

PMID- 20144741
TI  - Pancreatic endocrine carcinoma protruding from the major papilla.

PMID- 20144742
TI  - Xanthohumol inhibits IL-12 production and reduces chronic allergic contact
      dermatitis.
AB  - Xanthohumol (XN) and its related compounds were evaluated for their effects on
      modulating the production of interleukin (IL)-12, the most important factor
      driving T helper 1 immune responses. XN showed the strongest inhibitory effect on
      IL-12 production in macrophages stimulated by lipopolysaccharide (LPS) or
      LPS/interferon-gamma. Xanthohumol 4'-O-beta-D-glucopyranoside (XNG) inhibited IL
      12 production less effectively than XN. Isoxanthohumol and 8-prenylnaringenin
      showed comparatively lower inhibitory effects on IL-12 production than XNG. (2S)
      5-methoxy-8-prenylnaringenin 7-O-beta-D-glucopyranoside did not exert any effect
      on IL-12 production. We then tested how these compounds affected NF-kappaB
      binding activity to the kappaB site in the nucleus. The compounds inhibited
      kappaB binding in macrophages with the same potency order as IL-12 inhibition.
      Furthermore, we investigated whether XN, which showed the most effective
      reduction of IL-12 production, attenuated skin inflammation. Chronic allergic
      contact dermatitis, an experimental model for psoriasis, was used to determine
      the anti-inflammatory effects of XN in vivo. XN treatment reduced the degree of
      ear thickening induced by oxazolone. Taken together, XN might be effective as an
      anti-inflammatory agent to reduce skin inflammation by inhibiting IL-12
      production.

PMID- 20144743
TI  - Differential anti-inflammatory and anti-fibrotic activity of transplanted
      mesenchymal vs. hematopoietic stem cells in carbon tetrachloride-induced liver
      injury in mice.
AB  - Bone marrow stem cells nullify acquired and non-acquired diseases of liver
      through multiple strategies including antiinflammation. However, little is known
      about the in vivo mechanism of immunomodulation by stem cells in mediating liver
      cirrhosis. Mesenchymal stem cells (MSC) or hematopoietic stem cells (HSC)
      isolated from bone marrow of male mice were transplanted into female mice with
      acute liver inflammation. Serum levels of liver proteins and aminotransferase as
      well as hepatic antioxidant enzymes were estimated. Immunostaining for the
      expression of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6),
      alpha smooth muscle actin (alpha-SMA) and type I collagen proteins was carried
      out and the expression of these mRNAs was also studied. After post
      transplantation, the levels of serum albumin and aminotransferases became normal
      and the levels of antioxidants were significantly high in the MSC treated mice
      compared to HSC and control mice. Necrotic cells and invasion of neutrophils were
      not observed in histological sections of liver of MSC treated mice.
      Immunostaining showed that IL-6 and TNF-alpha were not expressed in the MSC
      treated mice when compared to the control and HSC treated mice. alpha-SMA
      representing activated myofibroblasts and type I collagen were not expressed in
      MSC treated group. These inflammatory and fibrogenic results were further
      confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The acute
      inflammation ended with the formation of fibrosis in the HSC and control groups
      by the uncontrolled immunoreactions. Protection mechanism of MSC therapy against
      injury and fibrosis in the liver occurs by the suppression of inflammation. Our
      findings suggest that bone marrow MSC are capable of alleviating the
      immunoreactions leading to the fibrosis in the liver.

PMID- 20144744
TI  - The worldwide gradient of autoimmune conditions.
AB  - Among the numerous consequences of globalization, the dissemination of scientific
      research allows real-time comparisons of clinical and basic experimental data
      between different geographical areas. As a result, the field of geoepidemiology
      is now vigorously supported by multiple lines of evidence. This special issue of
      Autoimmunity Reviews is dedicated to the 2010 International Congress on
      Autoimmunity and aims to provide a state-of-the-art representation of what is
      currently known in the field of geoepidemiology for autoimmune diseases. The
      obvious implications of these observations is a role for environmental factors.
      We will herein review selected publications from prominent scientific journals to
      provide the bases to understand some of the lines of evidence proposed in the
      subsequent papers of this comprehensive volume. The ultimate goal is thus to
      define whether geoepidemiology should be considered a new challenge for
      autoimmunologists.

PMID- 20144745
TI  - Sixth school in systemic autoimmune diseases.

PMID- 20144746
TI  - Calcium-strontium mixed phosphate as novel injectable and radio-opaque hydraulic
      cement.
AB  - Sterile calcium hydrogenophosphate dihydrate (DCPD) (CaHPO(4).2H(2)O), calcium
      oxide and strontium carbonate powders were mixed in various liquid phases. Among
      these, ammonium phosphate buffer (0.75 M, pH 6.9) led to a novel strontium
      containing calcium phosphate cement. At a 6/2.5/1.5 M ratio and for a liquid to
      powder ratio (L/P) of 0.5 mlg(-1), the initial paste was fluid and remained
      injectable for 12 min at 25 degrees C. It was easily obtained by mixing sterile
      powders and the liquid phase using the push-pull technique, avoiding complex
      mixing apparatus. The cement set after 15 min at 37 degrees C and was hard after
      1h. The compressive strength was in the 20 MPa range, a value higher than that
      generally assigned to trabecular bone (5-15MPa). This strength appeared
      sufficient for repairing non-loading sites or reinforcing osteoporotic vertebrae
      (vertebroplasty). After setting, the initial mixture formed a strontium-calcium
      deficient carbonate apatite. The radio-opacity of the resulting cement was three
      times greater than that of cortical bone because of the presence of strontium
      ions, a feature that complies with the requirements for vertebroplasty.
      Furthermore, the cement powder remained stable and retained its properties for at
      least 4 years.

PMID- 20144747
TI  - Osteogenic differentiation of bone marrow stromal cells on poly(epsilon
      caprolactone) nanofiber scaffolds.
AB  - Nanofiber poly(epsilon-caprolactone) (PCL) scaffolds were fabricated by
      electrospinning, and their ability to enhance the osteoblastic behavior of marrow
      stromal cells (MSCs) in osteogenic media was investigated. MSCs were isolated
      from Wistar rats and cultured on nanofiber scaffolds to assess short-term
      cytocompatibility and long-term phenotypic behavior. Smooth PCL substrates were
      used as control surfaces. The short-term cytocompatibility results indicated that
      nanofiber scaffolds supported greater cell adhesion and viability compared with
      control surfaces. In osteogenic conditions, MSCs cultured on nanofiber scaffolds
      also displayed increased levels of alkaline phosphatase activity for 3 weeks of
      culture. Calcium phosphate mineralization was substantially accelerated on
      nanofiber scaffolds compared to control surfaces as indicated through von Kossa
      and calcium staining, scanning electron microscopy and energy-dispersive X-ray
      spectroscopy. Increased levels of intra- and extracellular levels of osteocalcin
      and osteopontin were observed on nanofiber scaffolds using immunofluorescence
      techniques after 3 weeks of culture. These results demonstrate the enhanced
      tissue regeneration property of nanofiber scaffolds, which may be of potential
      use for engineering osteogenic scaffolds for orthopedic applications.

PMID- 20144748
TI  - Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral
      insulin delivery.
AB  - In the present study thiol functionalized polymethacrylic acid-polyethylene
      glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an
      oral insulin delivery system. Thiol modification was achieved by grafting
      cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP).
      Swelling and insulin loading/release experiments were conducted on these
      particles. The ability of these particles to inhibit protease enzymes was
      evaluated under in vitro experimental conditions. Insulin transport experiments
      were performed on Caco-2 cell monolayers and excised intestinal tissue with an
      Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in
      reducing the blood glucose level in streptozotocin-induced diabetic rats was
      investigated. Thiolated hydrogel microparticles showed less swelling and had a
      lower insulin encapsulation efficiency as compared with unmodified PCP particles.
      PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in
      vitro conditions. Thiolation was an effective strategy to improve insulin
      absorption across Caco-2 cell monolayers, however, the effect was reduced in the
      experiments using excised rat intestinal tissue. Nevertheless, functionalized
      microparticles were more effective in eliciting a pharmacological response in
      diabetic animal, as compared with unmodified PCP microparticles. From these
      studies thiolation of hydrogel microparticles seems to be a promising approach to
      improve oral delivery of proteins/peptides.

PMID- 20144749
TI  - Preparation, characterization and in vitro analysis of novel structured
      nanofibrous scaffolds for bone tissue engineering.
AB  - In a previous study, a three-dimensional nanofibrous spiral scaffold for bone
      tissue engineering was developed, which showed enhanced human osteoblast cell
      attachment, proliferation and differentiation compared with traditional cylinder
      scaffolds, owing to the incorporation of spiral structures and nanofiber.
      However, the application of these scaffolds to bone tissue engineering was
      limited by their weak mechanical strength. This limitation triggered the design
      for novel structured scaffolds with reinforced physical characteristics. In this
      study, spiral polycaprolactone (PCL) nanofibrous scaffolds were inserted into
      poly(lactide-co-glycolide) (PLGA) microsphere sintered tubular scaffolds to form
      integrated scaffolds to provide mechanical properties and bioactivity appropriate
      for bone tissue engineering. Four experiment groups were designed: PLGA cylinder
      scaffold; PLGA tubular scaffold; PLGA tubular scaffold with PCL spiral structured
      inner core; PLGA tubular scaffold with PCL nanofiber containing spiral structured
      inner core. The morphology, porosity and mechanical properties of the scaffolds
      were characterized. Furthermore, human osteoblastic cells were seeded on these
      scaffolds, and the cell attachment, proliferation, differentiation and
      mineralized matrix deposition on the scaffolds were evaluated. The integrated
      scaffolds had Young's modulus 250-300 MPa, and compressive strength 8-11 MPa
      under uniaxial compression. With the addition of an inner highly porous insert to
      the tubular shell, human osteoblast cells seeded on the integrated scaffolds
      showed slightly higher cell proliferation, 20-25% more alkaline phosphatase
      expression and twofold higher calcium deposition than those on the cylinder and
      tubular scaffolds. Furthermore, compared with sintered PLGA cylinder scaffolds,
      the integrated scaffolds allowed better cellular infiltration Therefore, this
      design demonstrates great potential for integrated scaffolds in bone tissue
      engineering applications.

PMID- 20144750
TI  - Impact of nanopore morphology on cell viability on mesoporous polymer and carbon
      surfaces.
AB  - Topography at the nanoscale can lead to dramatic changes in the adhesion of cells
      to surfaces and their subsequent viability. For biological applications,
      including tissue engineering and cell-based sensing, the large internal surface
      area of ordered mesoporous carbons provides an opportunity for enhanced
      sensitivity and performance, but the mesostructure also affects the topography of
      the material. In this work, we probe the viability and adhesion of osteoblasts on
      ordered mesoporous materials with different morphologies and matrix chemistries.
      FDU-15 (hexagonal) and FDU-16 (cubic) films were processed at either 350 degrees
      C (polymeric) or 800 degrees C (carbon) to provide these different materials. For
      the films processed at 350 degrees C, the cell adhesion was markedly improved on
      the mesoporous films in comparison to a dense film analog, consistent with many
      reports in the literature that nanostructuring of surfaces improves the viability
      and adhesion of osteoblasts. Conversely, osteoblast adhesion was reduced on the
      carbonized surfaces processed at 800 degrees C when ordered mesopores were
      introduced, particularly for the cubic mesostructure (FDU-16). We attribute the
      decrease in cell adhesion to the propensity of the ordered mesoporous carbon
      films to sorb organics from aqueous solution, which could lead to removal of
      adhesion-promoting compounds at the film surface. These results suggest that cell
      viability on mesoporous polymer and carbon films can be controlled through simple
      changes in the pyrolysis temperature.

PMID- 20144751
TI  - Essential modification of the Sircol Collagen Assay for the accurate
      quantification of collagen content in complex protein solutions.
AB  - Collagen contains the unique imino acid hydroxyproline (HyPro), which is involved
      in the stabilization of this triple helical molecule. The concentration of HyPro
      is customarily used to calculate the total collagen content in a cell culture
      environment and in acid hydrolysates of normal and pathophysiological tissues.
      Radiolabelling, chromatographic and calorimetric assays have been developed over
      the years for the accurate determination of collagen content through HyPro
      estimation. Recently, the Sircol Collagen Assay (SCA) has been almost exclusively
      adopted as the fastest and simplest colorimetric method for the determination of
      collagen concentration in complex protein solutions. We show here that the
      colorimetric SCA, which is based on the binding of Sirius red (SR) to collagen,
      is flawed by interference of non-collagenous proteins (e.g. serum). In fact, we
      demonstrate that SCA in cell culture systems and tissue hydrolysates results in a
      dramatic overestimation of collagen content ranging from 3- to 24-fold. In order
      to rescue this otherwise very practical assay, we introduce a simple purification
      procedure that allows the removal of interfering non-collagenous proteins from
      culture media and tissue samples so that accurate measurements with SCA are now
      possible.

PMID- 20144752
TI  - Surgical training and the European Working Time Directive: The role of informal
      workplace learning.
AB  - The introduction of European Working Time Directive, limiting doctors' working
      hours to 48 per week, has caused recent controversy within the profession. The
      Royal College of Surgeons of England in particular has been one of the loudest
      critics of the legislation. One of the main concerns is regarding the negative
      impact on training hours for those embarking on surgical careers. Simulation
      technology has been suggested as a method to overcome this reduction in hospital
      training hours, and research suggests that this is a good substitute for
      operative training in a theatre. However, modern educational theory emphasises
      the power of informal workplace learning in postgraduate education, and the
      essential role of experience in training future surgeons.

PMID- 20144754
TI  - Nups take leave of the nuclear envelope to regulate transcription.
AB  - Although components of the nuclear pore complex have been implicated in gene
      regulation independent of their role at the nuclear envelope, the evidence so far
      has been indirect. Capelson et al. (2010) and Kalverda et al. (2010) now reveal
      that certain nucleoporins are actively involved in transcription inside the
      nucleoplasm of Drosophila cells.

PMID- 20144755
TI  - USP10: friend and foe.
AB  - The tumor suppressor protein p53, a crucial player in the DNA damage response, is
      regulated in many ways, most notably through ubiquitination. In this issue, Yuan
      et al. (2010) identify the deubiquitinating protease USP10 as a new regulator of
      p53 in the DNA damage response and tumor development.

PMID- 20144756
TI  - Shedding light on sperm pHertility.
AB  - The acquisition of fertilization capacity by sperm is regulated by intracellular
      pH (pH(i)), but the transport pathways that regulate pH(i) are not well
      understood. Lishko et al. (2010) now report that Hv1, the voltage-sensitive
      proton channel, is present in human sperm and is an important regulator of the
      functional maturation of sperm.

PMID- 20144758
TI  - Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated
      proton channel.
AB  - Human spermatozoa are quiescent in the male reproductive system and must undergo
      activation once introduced into the female reproductive tract. This process is
      known to require alkalinization of sperm cytoplasm, but the mechanism responsible
      for transmembrane proton extrusion has remained unknown because of the inability
      to measure membrane conductance in human sperm. Here, by successfully patch
      clamping human spermatozoa, we show that proton channel Hv1 is their dominant
      proton conductance. Hv1 is confined to the principal piece of the sperm
      flagellum, where it is expressed at unusually high density. Robust flagellar Hv1
      dependent proton conductance is activated by membrane depolarization, an alkaline
      extracellular environment, endocannabinoid anandamide, and removal of
      extracellular zinc, a potent Hv1 blocker. Hv1 allows only outward transport of
      protons and is therefore dedicated to inducing intracellular alkalinization and
      activating spermatozoa. The importance of Hv1 for sperm activation makes it an
      attractive target for controlling male fertility.

PMID- 20144757
TI  - Methods in mammalian autophagy research.
AB  - Autophagy has been implicated in many physiological and pathological processes.
      Accordingly, there is a growing scientific need to accurately identify, quantify,
      and manipulate the process of autophagy. However, as autophagy involves dynamic
      and complicated processes, it is often analyzed incorrectly. In this Primer, we
      discuss methods to monitor autophagy and to modulate autophagic activity, with a
      primary focus on mammalian macroautophagy.

PMID- 20144759
TI  - Double-stranded RNA-dependent protein kinase links pathogen sensing with stress
      and metabolic homeostasis.
AB  - As chronic inflammation is a hallmark of obesity, pathways that integrate
      nutrient- and pathogen sensing pathways are of great interest in understanding
      the mechanisms of insulin resistance, type 2 diabetes, and other chronic
      metabolic pathologies. Here, we provide evidence that double-stranded RNA
      dependent protein kinase (PKR) can respond to nutrient signals as well as
      endoplasmic reticulum (ER) stress and coordinate the activity of other critical
      inflammatory kinases such as the c-Jun N-terminal kinase (JNK) to regulate
      insulin action and metabolism. PKR also directly targets and modifies insulin
      receptor substrate and hence integrates nutrients and insulin action with a
      defined pathogen response system. Dietary and genetic obesity features marked
      activation of PKR in adipose and liver tissues and absence of PKR alleviates
      metabolic deterioration due to nutrient or energy excess in mice. These findings
      demonstrate PKR as a critical component of an inflammatory complex that responds
      to nutrients and organelle dysfunction.

PMID- 20144760
TI  - Nucleoporins directly stimulate expression of developmental and cell-cycle genes
      inside the nucleoplasm.
AB  - Nuclear pore complexes (NPCs) mediate transport across the nuclear envelope. In
      yeast, they also interact with active genes, attracting or retaining them at the
      nuclear periphery. In higher eukaryotes, some NPC components (nucleoporins) are
      also found in the nucleoplasm, with a so far unknown function. We have
      functionally characterized nucleoporin-chromatin interactions specifically at the
      NPC or within the nucleoplasm in Drosophila. We analyzed genomic interactions of
      full-length nucleoporins Nup98, Nup50, and Nup62 and nucleoplasmic and NPC
      tethered forms of Nup98. We found that nucleoporins predominantly interacted with
      transcriptionally active genes inside the nucleoplasm, in particular those
      involved in developmental regulation and the cell cycle. A smaller set of
      nonactive genes interacted with the NPC. Genes strongly interacting with
      nucleoplasmic Nup98 were downregulated upon Nup98 depletion and activated on
      nucleoplasmic Nup98 overexpression. Thus, nucleoporins stimulate developmental
      and cell-cycle gene expression away from the NPC by interacting with these genes
      inside the nucleoplasm.

PMID- 20144761
TI  - Chromatin-bound nuclear pore components regulate gene expression in higher
      eukaryotes.
AB  - Nuclear pore complexes have recently been shown to play roles in gene activation;
      however their potential involvement in metazoan transcription remains unclear.
      Here we show that the nucleoporins Sec13, Nup98, and Nup88, as well as a group of
      FG-repeat nucleoporins, bind to the Drosophila genome at functionally distinct
      loci that often do not represent nuclear envelope contact sites. Whereas Nup88
      localizes to silent loci, Sec13, Nup98, and a subset of FG-repeat nucleoporins
      bind to developmentally regulated genes undergoing transcription induction.
      Strikingly, RNAi-mediated knockdown of intranuclear Sec13 and Nup98 specifically
      inhibits transcription of their target genes and prevents efficient reactivation
      of transcription after heat shock, suggesting an essential role of NPC components
      in regulating complex gene expression programs of multicellular organisms.

PMID- 20144762
TI  - RIG-I detects viral genomic RNA during negative-strand RNA virus infection.
AB  - RIG-I is a key mediator of antiviral immunity, able to couple detection of
      infection by RNA viruses to the induction of interferons. Natural RIG-I
      stimulatory RNAs have variously been proposed to correspond to virus genomes,
      virus replication intermediates, viral transcripts, or self-RNA cleaved by RNase
      L. However, the relative contribution of each of these RNA species to RIG-I
      activation and interferon induction in virus-infected cells is not known. Here,
      we use three approaches to identify physiological RIG-I agonists in cells
      infected with influenza A virus or Sendai virus. We show that RIG-I agonists are
      exclusively generated by the process of virus replication and correspond to full
      length virus genomes. Therefore, nongenomic viral transcripts, short replication
      intermediates, and cleaved self-RNA do not contribute substantially to interferon
      induction in cells infected with these negative strand RNA viruses. Rather,
      single-stranded RNA viral genomes bearing 5'-triphosphates constitute the natural
      RIG-I agonists that trigger cell-intrinsic innate immune responses during
      infection.

PMID- 20144763
TI  - Distinct protein domains and expression patterns confer divergent axon guidance
      functions for Drosophila Robo receptors.
AB  - The orthogonal array of axon pathways in the Drosophila CNS is constructed in
      part under the control of three Robo family axon guidance receptors: Robo1, Robo2
      and Robo3. Each of these receptors is responsible for a distinct set of guidance
      decisions. To determine the molecular basis for these functional specializations,
      we used homologous recombination to create a series of 9 "robo swap" alleles:
      expressing each of the three Robo receptors from each of the three robo loci. We
      demonstrate that the lateral positioning of longitudinal axon pathways relies
      primarily on differences in gene regulation, not distinct combinations of Robo
      proteins as previously thought. In contrast, specific features of the Robo1 and
      Robo2 proteins contribute to their distinct functions in commissure formation.
      These specializations allow Robo1 to prevent crossing and Robo2 to promote
      crossing. These data demonstrate how diversification of expression and structure
      within a single family of guidance receptors can shape complex patterns of
      neuronal wiring.

PMID- 20144764
TI  - Aplysia CPEB can form prion-like multimers in sensory neurons that contribute to
      long-term facilitation.
AB  - Prions are proteins that can assume at least two distinct conformational states,
      one of which is dominant and self-perpetuating. Previously we found that a
      translation regulator CPEB from Aplysia, ApCPEB, that stabilizes activity
      dependent changes in synaptic efficacy can display prion-like properties in
      yeast. Here we find that, when exogenously expressed in sensory neurons, ApCPEB
      can form an amyloidogenic self-sustaining multimer, consistent with it being a
      prion-like protein. In addition, we find that conversion of both the exogenous
      and the endogenous ApCPEB to the multimeric state is enhanced by the
      neurotransmitter serotonin and that an antibody that recognizes preferentially
      the multimeric ApCPEB blocks persistence of synaptic facilitation. These results
      are consistent with the idea that ApCPEB can act as a self-sustaining prion-like
      protein in the nervous system and thereby might allow the activity-dependent
      change in synaptic efficacy to persist for long periods of time.

PMID- 20144765
TI  - SnapShot: pathways of antiviral innate immunity.

PMID- 20144766
TI  - Evolutionary ecology: when pollinators are also herbivores.
AB  - Plants often face a dilemma in attracting mutualists versus deterring
      antagonists. This dilemma may be exceptionally challenging when the mutualist and
      antagonist are the same visitor. It has now been demonstrated how plants can
      resolve this conflict through a novel change in flowering traits.

PMID- 20144767
TI  - Cell cycle: the art of multi-tasking.
AB  - Separase is the protease that cleaves the cohesive link between sister chromatids
      to trigger chromosome segregation in mitosis and meiosis. This enzyme is known to
      orchestrate additional mitotic events and we now gain new insight into how it
      promotes cytokinesis in the nematode Caenorhabditis elegans.

PMID- 20144768
TI  - Social evolution: sick ants face death alone.
AB  - Social insects not only live altruistically, they die so: a new study reveals
      that moribund ants abandon their nests to die in seclusion, which reduces the
      risk of transmitting diseases to relatives.

PMID- 20144769
TI  - Bacterial invasion: linking autophagy and innate immunity.
AB  - Crohn's disease is a chronic inflammatory bowel disorder that has been associated
      with polymorphisms in the genes encoding the pattern-recognition receptor NOD2
      and the autophagic regulator ATG16L1. A new study demonstrates that NOD2 recruits
      ATG16L1 at bacterial entry sites, thereby bridging innate immunity and autophagy.

PMID- 20144770
TI  - siRNAs: the hidden face of the small RNA world.
AB  - MicroRNAs are believed to control many physiological processes in animals. Now,
      two studies show that some of their presumptive functions are actually fulfilled
      by another class of RNAs - siRNAs.

PMID- 20144771
TI  - Short RNAs: how big is this iceberg?
AB  - Recent studies have reported the identification of piwi-associated RNAs (piRNAs)
      in Drosophila somatic cells. Interestingly, these piRNAs derive from the 3'
      untranslated regions of a subset of transcribed protein-coding genes and,
      experimentation suggests, might control the expression of other protein-coding
      transcripts. Studies of additional organisms support the new pathway's presence
      across animals.

PMID- 20144773
TI  - Entosis.

PMID- 20144772
TI  - Phototransduction and the evolution of photoreceptors.
AB  - Photoreceptors in metazoans can be grouped into two classes, with their
      photoreceptive membrane derived either from cilia or microvilli. Both classes use
      some form of the visual pigment protein opsin, which together with 11-cis
      retinaldehyde absorbs light and activates a G-protein cascade, resulting in the
      opening or closing of ion channels. Considerable attention has recently been
      given to the molecular evolution of the opsins and other photoreceptor proteins;
      much is also known about transduction in the various photoreceptor types. Here we
      combine this knowledge in an attempt to understand why certain photoreceptors
      might have conferred particular selective advantages during evolution. We suggest
      that microvillar photoreceptors became predominant in most invertebrate species
      because of their single-photon sensitivity, high temporal resolution, and large
      dynamic range, and that rods and a duplex retina provided primitive chordates and
      vertebrates with similar sensitivity and dynamic range, but with a smaller
      expenditure of ATP.

PMID- 20144774
TI  - Extracellular regulation of BMP signaling.
AB  - In the developing organism, cells differentiate, divide and die as part of groups
      of hundreds or thousands of cells called 'morphogenetic fields'. Fields have the
      remarkable property of self-regulation: for example, if the forelimb field is
      bisected, each half can give rise to a complete limb after transplantation, as
      discovered by Ross Harrison in 1918. Therefore, cells in the morphogenetic field
      are capable of long-range communication with each other in order to ascertain
      their position [1]. This positional information is relayed in the extracellular
      space in the form of concentration gradients of specific classes of extracellular
      molecules called 'morphogens' that trigger cellular responses by binding and
      activating cell surface receptors. Here, we focus on a family of morphogens
      called 'Bone Morphogenetic Proteins' (BMPs), which has provided a new paradigm
      for signaling regulation in the extracellular space.

PMID- 20144775
TI  - When your eyes see more than you do.
AB  - Visual information is used by the brain to construct a conscious experience of
      the visual world and to guide motor actions [1]. Here we report a study of how
      eye movements and perception relate to each other. We compared the ability of
      human observers to perceive image motion with the reliability of their eyes to
      track the motion of a target [2], [3] and [4], the goal being to test whether
      both motor and sensory processes are based on the same set of signals and limited
      by a shared source of noise [2] and [4]. We found that the oculomotor system can
      detect fluctuations in the velocity of a moving target better than the observer.
      Surprisingly, in some conditions, eye movements reliably respond to the velocity
      fluctuations of a moving target that are otherwise perceptually invisible to the
      subjects. The implication is that visual motion signals exist in the brain that
      can be used to guide motor actions without evoking a perceptual outcome nor being
      accessible to conscious scrutiny.

PMID- 20144776
TI  - Evidence for contemporary evolution during Darwin's lifetime.
AB  - Darwin's On the Origin of Species[1] introduced the world to the most fundamental
      concept in biological sciences - evolution. However, in the 150 years following
      publication of his seminal work, much has been made of the fact that Darwin was
      missing at least one crucial link in his chain of evidence - he had no evidence
      for contemporary evolution through natural selection. Indeed, as one commentator
      noted on the centenary of the publication of Origin, "Had Darwin observed
      industrial melanism he would have seen evolution occurring not in thousands of
      years but in thousands of days - well within his lifetime. He would have
      witnessed the consummation and confirmation of his life's work"[2].

PMID- 20144777
TI  - Vision: the retinoid cycle in Drosophila.
AB  - It was commonly accepted that the enzymatic pathway regenerating bleached visual
      pigments is present in vertebrate but not invertebrate animals. New studies
      indicate that this pathway is present in Drosophila and is vital for maintaining
      both the amount of visual pigment and photoreceptor health in light-exposed
      flies.

PMID- 20144778
TI  - Behavioral development: timing is everything.
AB  - A new study has found that bonobos take longer to reach adult levels of two
      behaviors than do chimpanzees, providing empirical support for the
      'paedomorphism' hypothesis among our closest relatives.

PMID- 20144779
TI  - A new member of the spindle orientation club: mammalian intestinal stem cells.
AB  - Mitotic spindles are stereotypically oriented in many stem cells, often leading
      to asymmetric outcomes of stem cell division. In this issue of Cell Stem Cell,
      Nathke and colleagues (Quyn et al., 2010) report that mammalian intestinal stem
      cells exhibit an oriented spindle and asymmetry during division.

PMID- 20144780
TI  - Age-related changes in niche cells influence hematopoietic stem cell function.
AB  - In a recent issue of Nature, Mayack et al. (2010) use young and old parabiotic
      mice to show that systemic signals from the young parabiont rejuvenate
      hematopoietic stem cell function via the microenvironmental niche.

PMID- 20144781
TI  - A dominant role of the hair follicle stem cell niche in regulating melanocyte
      stemness.
AB  - Melanocyte and hair follicle bulge stem cells share a common niche. In this issue
      of Cell Stem Cell, Nishimura et al. (2010) show that hair follicle stem cells, by
      expressing high levels of TGF-beta2, regulate the quiescence, the stemness, and
      the long-term renewal of melanocyte stem cells.

PMID- 20144782
TI  - NO Signals from the Cancer Stem Cell Niche.
AB  - Characterization of signaling pathways that control cancer stem cells may lead to
      more effective treatments against cancer. In this issue of Cell Stem Cell, a
      study by Charles et al. (2010) identifies the NO and Notch pathways as important
      regulators of the perivascular niche of cancer stem cells in glioma.

PMID- 20144783
TI  - A legal defense for compensating research egg donors.
AB  - Given the continued need for human eggs for hESCs, this article analyzes and
      refutes the legal theories against compensating research egg donors, contrasts
      the legal histories of compensating reproductive donors and human subjects with
      noncompensation for ESC donors, and suggests that limited compensation is legally
      defensible.

PMID- 20144784
TI  - Stem cells and the niche: a dynamic duo.
AB  - Stem cell niches are dynamic microenvironments that balance stem cell activity to
      maintain tissue homeostasis and repair throughout the lifetime of an organism.
      The development of strategies to monitor and perturb niche components has
      provided insight into the responsive nature of the niche and offers a framework
      to uncover how disruption of normal stem cell niche function may contribute to
      aging and disease onset and progression. Additional work in the identification of
      genetic factors that regulate the formation, activity, and size of stem cell
      niches will facilitate incorporation of the niche into stem cell-based therapies
      and regenerative medicine.

PMID- 20144785
TI  - Sprouty1 regulates reversible quiescence of a self-renewing adult muscle stem
      cell pool during regeneration.
AB  - Satellite cells are skeletal muscle stem cells capable of self-renewal and
      differentiation after transplantation, but whether they contribute to endogenous
      muscle fiber repair has been unclear. The transcription factor Pax7 marks
      satellite cells and is critical for establishing the adult satellite cell pool.
      By using a lineage tracing approach, we show that after injury, quiescent adult
      Pax7(+) cells enter the cell cycle; a subpopulation returns to quiescence to
      replenish the satellite cell compartment, while others contribute to muscle fiber
      formation. We demonstrate that Sprouty1 (Spry1), a receptor tyrosine kinase
      signaling inhibitor, is expressed in quiescent Pax7(+) satellite cells in
      uninjured muscle, downregulated in proliferating myogenic cells after injury, and
      reinduced as Pax7(+) cells re-enter quiescence. We show that Spry1 is required
      for the return to quiescence and homeostasis of the satellite cell pool during
      repair. Our results therefore define a role for Spry1 in adult muscle stem cell
      biology and tissue repair.

PMID- 20144786
TI  - Key roles for transforming growth factor beta in melanocyte stem cell
      maintenance.
AB  - Melanocyte stem cells in the bulge area of hair follicles are responsible for
      hair pigmentation, and defects in them cause hair graying. Here we describe the
      process of melanocyte stem cell entry into the quiescent state and show that
      niche-derived transforming growth factor beta (TGF-beta) signaling plays
      important roles in this process. In vitro, TGF-beta not only induces reversible
      cell cycle arrest, but also promotes melanocyte immaturity by downregulating
      MITF, the master transcriptional regulator of melanocyte differentiation, and its
      downstream melanogenic genes. In vivo, TGF-beta signaling is activated in
      melanocyte stem cells when they reenter the quiescent noncycling state during the
      hair cycle and this process requires Bcl2 for cell survival. Furthermore,
      targeted TGF-beta type II receptor (TGFbRII) deficiency in the melanocyte lineage
      causes incomplete maintenance of melanocyte stem cell immaturity and results in
      mild hair graying. These data demonstrate that the TGF-beta signaling pathway is
      one of the key niche factors that regulate melanocyte stem cell immaturity and
      quiescence.

PMID- 20144787
TI  - Perivascular nitric oxide activates notch signaling and promotes stem-like
      character in PDGF-induced glioma cells.
AB  - eNOS expression is elevated in human glioblastomas and correlated with increased
      tumor growth and aggressive character. We investigated the potential role of
      nitric oxide (NO) activity in the perivascular niche (PVN) using a genetic
      engineered mouse model of PDGF-induced gliomas. eNOS expression is highly
      elevated in tumor vascular endothelium adjacent to perivascular glioma cells
      expressing Nestin, Notch, and the NO receptor, sGC. In addition, the NO/cGMP/PKG
      pathway drives Notch signaling in PDGF-induced gliomas in vitro, and induces the
      side population phenotype in primary glioma cell cultures. NO also increases
      neurosphere forming capacity of PDGF-driven glioma primary cultures, and enhances
      their tumorigenic capacity in vivo. Loss of NO activity in these tumors
      suppresses Notch signaling in vivo and prolongs survival of mice. This mechanism
      is conserved in human PDGFR amplified gliomas. The NO/cGMP/PKG pathway's
      promotion of stem cell-like character in the tumor PVN may identify therapeutic
      targets for this subset of gliomas.

PMID- 20144789
TI  - Spindle orientation bias in gut epithelial stem cell compartments is lost in
      precancerous tissue.
AB  - The importance of asymmetric divisions for stem cell function and maintenance is
      well established in the developing nervous system and the skin; however, its role
      in gut epithelium and its importance for tumorigenesis is still debated. We
      demonstrate alignment of mitotic spindles perpendicular to the apical surface
      specifically in the stem cell compartments of mouse and human intestine and
      colon. This orientation correlates with the asymmetric retention of label
      retaining DNA. Both the preference for perpendicular spindle alignment and
      asymmetric label retention are lost in precancerous tissue heterozygous for the
      adenomatous polyposis coli tumor suppressor (Apc). This loss correlates with cell
      shape changes specifically in the stem cell compartment. Our data suggest that
      loss of asymmetric division in stem cells might contribute to the oncogenic
      effect of Apc mutations in gut epithelium.

PMID- 20144788
TI  - Polycomb-like 2 associates with PRC2 and regulates transcriptional networks
      during mouse embryonic stem cell self-renewal and differentiation.
AB  - Polycomb group (PcG) proteins are conserved epigenetic transcriptional repressors
      that control numerous developmental gene expression programs and have recently
      been implicated in modulating embryonic stem cell (ESC) fate. We identified the
      PcG protein PCL2 (polycomb-like 2) in a genome-wide screen for regulators of self
      renewal and pluripotency and predicted that it would play an important role in
      mouse ESC-fate determination. Using multiple biochemical strategies, we provide
      evidence that PCL2 is a Polycomb Repressive Complex 2 (PRC2)-associated protein
      in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened self-renewal
      characteristics, defects in differentiation, and altered patterns of histone
      methylation. Integration of global gene expression and promoter occupancy
      analyses allowed us to identify PCL2 and PRC2 transcriptional targets and draft
      regulatory networks. We describe the role of PCL2 in both modulating
      transcription of ESC self-renewal genes in undifferentiated ESCs as well as
      developmental regulators during early commitment and differentiation.

PMID- 20144790
TI  - [Factors associated with a significant functional gain and new
      institutionalisation in rehabilitated patients admitted to a long term care
      unit].
AB  - BACKGROUND AND OBJECTIVES: To determine which factors are associated with a
      functional gain above 19 on Barthel's index (CSFG) and also factors associated
      with a new post-discharge institutionalisation (NPDI) in patients who a underwent
      rehabilitation intervention whilst admitted to a medium long term care unit.
      PATIENTS AND METHODS: Prospective study of patients admitted between 2000 and
      2005 who underwent a rehabilitation intervention. Demographic, mind-body and
      laboratory data were collected. RESULTS: 153 patients were selected for the first
      aim and 148 for the second. 53.3% of the patients achieved a CSFG. The incidence
      of NPDI was of 23.7%. The following factors were associated with a CSFG in the
      multivariate analysis: age (OR: 0.95), female gender (OR: 0.35), rehabilitation
      objective at admission (OR: 7.43), infectious disease as primary diagnosis (OR:
      10.35), mild dependence at admission (OR: 0.09), absence of malnutrition (OR:
      3.12), high comorbidity (OR: 0.31), need of wound care (OR: 0.36) and ansiolitic
      intake at admission (OR: 9.11). Likewise, the following factors were associated
      with the occurrence of a NPDI: age (OR: 1.12), long-term care objective at
      admission (OR: 7.84), chronic lung disease (OR: 0.29), number of drug
      prescriptions at admission (OR: 0.82), neuroleptic intake at admission (OR:
      7.42), living with relatives (OR: 0.29) and nosocomial infection during the
      hospital stay (OR: 2.99). CONCLUSIONS: Several factors have been associated to
      CSFG and NPDI and they would be useful to optimise rehabilitation resources and
      to plan post-discharge institutional transfer.

PMID- 20144791
TI  - [Appropriateness of empiric antibiotic therapy in urinary tract infection in
      emergency room].
AB  - INTRODUCTION: To describe characteristics of urinary tract infections attended in
      an Emergency Department. To assess antibiotic prescription and inappropriate
      treatment implications. METHODS: Adults patients attended in an Emergency
      Department during 2 months with UTI confirmed with urocultive were included.
      Appropriate antibiotic treatment was considered if the first antibiotic used was
      sensitive. We compared patients with appropriate and inappropriate antibiotic
      treatment. A logistic regression was performed to evaluate variables associated
      to inappropriate antibiotic treatment. RESULTS: A total of 151 patients were
      included (61% women, 67.1[22.3] years). Comorbidity was present in 63% of
      patients. Urinary sepsis was the most frequent diagnosis (32.5%). E coli was
      isolated in 65.6% of cases, and 10% presented bacteremia. Percentage of
      inappropriate antibiotic treatment was 20.5. It was associated (uncontrolled
      analysis) with male gender, elder patients, recent urinary simptoms, urologic
      manipulation more than 1 month ago, previous antibiotic use (especially
      ciprofloxacin or amoxicillin-clavulanate) and presentation with urinary sepsis.
      Logistic regression analysis showed association only with age (HR 0.978 per year,
      CI95% 0.957-1, p=0.029) and previous antibiotic use (HR 0.298, CI95% 0.098-0.901,
      p=0.05). Patients with inappropriate antibiotic treatment did not have higher
      mortality. CONCLUSIONS: Inappropriate antibiotic treatment for UTI in Emergency
      Department is relatively frequent and it is associated to older age and previous
      antibiotic use.

PMID- 20144792
TI  - [Infection due to Rhodococcus equi in HIV infected patients: four cases].
AB  - INTRODUCTION: Incidence of Rhodococcus equi (R. equi) infection is increasing
      parallel to a greater prevalence of immunosupressed patients. This study aims to
      describe clinico-epidemiological characteristics of R. equi infections in a
      single hospital. METHODS: Retrospective, observational study that includes any
      patient diagnosed of R. equi infection during the 1999-2007 period. Clinical and
      epidemiological characteristics were recorded. RESULTS: Four patients were
      diagnosed of R. equi infection, with a mean age of 37.75+/-9.94 years old. All of
      them were male, infected with human immunodeficiency virus, and showed severe
      immunosuppression (mean CD4+ lymphocyte count of 83+/-55.2 cells/microl).
      Respiratory symptoms and cavitary pulmonary lesions were constantly present. R.
      equi was always cultured in blood and respiratory secretions. CONCLUSIONS: R.
      equi infection is a rare disease that occurs predominantly in HIV infected
      patients, severely immunosuppressed patients and almost always causes cavitary
      pneumonia.

PMID- 20144793
TI  - [Integral geriatric assessment and functional recovery in middle-long stay
      units].

PMID- 20144794
TI  - [Therapeutic behavior to follow in the following clinical case: treatment of type
      2 diabetes].
AB  - A 62-year old woman with obesity, high blood pressure and type 2 diabetes
      mellitus (DM2) was referred to a Vascular Risk Unit of the Internal Medicine
      Department due to elevated HbA1C (8.1%) in spite of having taken metformin (850
      mg/12h) and glipizide (10 mg/12 h) regularly. She tries to exercise daily
      (walking 30 min) and has lost weight (from 5 to 12 kg) several times, but always
      regains what she has lost. Furthermore, she monitors her glucose levels in
      fasting every two weeks and generally has between 120 and 160 mg/dL. Her high
      blood pressure is being treated with enalapril/HCTZ and she also takes aspirin
      100mg/day and simvastatin 20 mg/day. It is seen in her family background that one
      brother died suddenly at 50 years of age. Her physical examination shows a BMI of
      32.4 Kg/m(2), and she has no edemas in the lower limbs. Her BP is 154/82 mmHg and
      creatinine 0.9 mg/dL. She has no microalbuminuria and her liver function is
      normal. What treatment do you think would be the more appropriate? 1 - Add
      glitazones. 2 - Add incretin mimetics (GLP 1/ DPP-4). 3 - Slow acting insulin.

PMID- 20144798
TI  - [SEMI, in the Scientific Society of the XXI Century: what we did during 2009 and
      what we are going to do in 2010].
AB  - The principal actions carried out by the Spanish Society of Internal Medicine
      (SEMI) during the last year are reviewed in this work. The projects that are
      going to be developed immediately in 2010 are also announced. In 2009, it was
      aimed to improve the communication policy, consolidate and strengthen the
      structure of the Society with the creation of a permanent committee, stimulate
      the activities of the strategic Work Groups and the promotion of new
      organizational models. A new Work Group was established on Internal Medicine in
      private practice. New projects and initiatives were also designed, such as the
      project of Hospital Discharge Report, Study of Residents and Internal Medicine in
      the University. These projects will be established within the next months and
      they will strengthen us as specialists of prestige. The SEMI is continuing along
      a positive pathway in its projection, modernization and search for the active
      participation of its members. The Journal, Revista Clinica Espanola, official
      publication of the SEMI, has experienced an important impulse with the new
      administrative team formed in the year 2009. Our journal should be a key piece in
      the future of the Society.

PMID- 20144799
TI  - [2009 report from the editors].
AB  - The editors of the Rev Clin Esp present the editorial course of action of the
      journal over the past year. We have up-dated the design of the journal, its
      contents (sections) and computerized the editorial process. We processed 467
      manuscripts and made an editorial decision on 402 of them between November 2008
      and October 2009. A total of 92 manuscripts (23%) were accepted. Fifteen (13%)
      out of the 119 original articles for which the editorial process was completed
      were accepted. Our goal for the year 2010 is to make the journal available on the
      Internet for all those who are subscribers to the Rev Clin Esp as well as for
      internal medicine residents (for which they must be members of each regional
      society). Other objectives of the editorial team are to edit the E-cases, for the
      journal to be a continuing education tool and that the coordinators of the work
      groups develop a monographic number at least once every two years. These actions
      aim to increase the impact factor and the quality of the Rev Clin Esp, official
      publication of the Spanish Society of Internal Medicine and of Spanish-speaking
      internal medicine physicians.

PMID- 20144800
TI  - [Hypoglycemia by intake of taurine].

PMID- 20144801
TI  - [Incidence of second non-hematologic malignancies in patients with multiple
      myeloma].

PMID- 20144802
TI  - [Eosinophilic esophagitis: four arguments to discuss].

PMID- 20144803
TI  - [Excessive dynamic airway collapse: a new disease].

PMID- 20144804
TI  - [Immediate care consultation. An experience of three years].

PMID- 20144805
TI  - [Acute bacterial meningitis in older people].
AB  - INTRODUCTION: The age distribution of acute bacterial meningitis (ABM) has
      shifted from children to adults. At the same time, older population is
      increasing. The aim of this study is to characterize ABM in elderly patients.
      MATERIAL AND METHODS: We reviewed the meningitis cases diagnosed at our hospital
      (1982-2006), including ABM cases defined by established criteria. Two groups were
      analyzed: elderly patients (aged > or =60) and young adults (aged 14-59).
      RESULTS: Ninety-five of 239 ABM (40%) were diagnosed in elderly patients, while
      144 (60%) were found in younger adults. In elderly people, 32% were nosocomial,
      49% had postoperative risk factors, and 24% were spontaneous infections. The
      combination of fever, neck stiffness, and altered mental status was present in
      45%. Elderly people presented altered mental status more often (p=0,002), had
      higher protein level (p=0,023) and higher percentage of positive cerebrospinal
      fluid culture (p=0,039). The most common pathogens were Streptococcus pneumoniae
      (20%), coagulase-negative Staphylococcus (14%) and Listeria monocytogenes (8%),
      whereas meningitis of unknown etiology was less common (p=0,014). Elderly
      patients had a higher mortality rate (19% vs. 6%, p=0,001), closely related to:
      age > or =years, altered mental status, absence of headache or vomiting,
      development of complications and systemic complications, and infection by Staph.
      aureus. In the multivariate model, age > or =75 years [OR=6,65; p=0,008], absence
      of headache [OR=0,15; p=0,003], and development of complications [OR=4,55;
      p=0,015] remained significantly associated with mortality. CONCLUSIONS: In
      elderly people, ABM affects patients with risk factors,and is predominantly due
      to Strep. pneumoniae. This age group has a higher mortality rate, which is
      associated with advanced age and development of complications.

PMID- 20144806
TI  - [Incidence of lower extremity amputations in Area 3 of Madrid. Retrospective
      study during the period 2001-2006].
AB  - OBJECTIVE: To quantify the Lower Extremity Amputations (LEA) incidence in
      population with and without diabetes mellitus (DM). MATERIAL AND METHODS:
      Retrospective cohort study of all the LEA carried out during 2001-2006 in area 3
      of Madrid, from the codification of the reports of discharge reports. RESULTS:
      310 LEA were carried out. The age-ajusted LEA incidence for any reason was
      19,2/10(5) inhabitants per year (27,2 y 11,2 for men and women respectively). 261
      were not-traumatic and non-tumoural (NTT) LEA, 76% were associated with DM and
      the incidence was 191/10(5) people with DM per year (95% confidence interval
      [CI(95)] 122-299) and 4,4/10(5) for people without DM per year (CI(95) 7-23),
      with a risk ratio of 44 (CI(95) 23-73). CONCLUSIONS: The LEA rates in population
      with o without diabetes are higher than the previously communicated in Madrid. It
      would appear convenient to design strategies to reduce the LEA rates.

PMID- 20144807
TI  - [Evaluation of high risk syncope referred from emergency department].
AB  - INTRODUCTION: High-risk syncope (over aged 60, abnormal electrocardiogram,
      syncope without prodromes and/or background of cardiovascular disease) is
      associated with high mortality. More detailed attention to that which may often
      be considered as an emergency should be given. We have evaluated the activity of
      a specialized service in the care of syncope in an internal medicine service.
      MATERIAL AND METHODS: We have collected a series of patients diagnosed in the
      emergency service of "syncope." The patients were referred to the specialized
      unit in the care of syncope and evaluated in less than 72h. We analyzed the tests
      made to establish a pathophysiological diagnosis of syncope. RESULTS: A total of
      107 consecutive patients were studied, 82 of whom met the criteria for being at
      risk of syncope. All underwent an echocardiography and outpatient Holter. A total
      of 23 studies were performed with tilt test, 4 electrophysiological studies were
      performed and 2 were implanted with an insertable Holter. A specific diagnosis
      could be established in 73 patients. Three patients were diagnosed with a
      neurological disease. The most frequent cause of the syncope was neuromediated
      (41 patients). After a mean follow-up of over 2 years, total mortality (9
      patients) was not related with the syncope. CONCLUSIONS: A specialized service in
      the care of high-risk syncope increases the percentage of patients with a
      definitive diagnosis.

PMID- 20144808
TI  - [Meningitis in the elderly: the importance of the astuteness of the physician for
      the diagnosis].

PMID- 20144809
TI  - [Malaria prophylaxis in the traveler].
AB  - Malaria is a preventable and curable disease. The risk zones are those tropical
      and subtropical regions of the countries with endemic malaria. These countries
      are visited by 125 million international tourists yearly and it is estimated that
      up to 30,000 fall sick with malaria. Prevention is done by: preventing
      transmission (using mosquito repellent, mosquito nets, etc.) and by preventing
      the disease by chemoprophylaxis. The latter aims to reduce the risk of suffering
      severe malaria, basically that produced by P. falciparum. It consists in the
      administration of antimalaria drugs before, during and after the trip. The choice
      of antimalaria drug will depend on the individual factors (allergies,
      contraindications, etc.) and mainly on the resistance of P. falciparum to these
      drugs. In areas with sensitivity to chloroquine, this should be the drug of
      choice and in those with resistances, three drugs have been recommended by both
      the CDC and WHO: Atovaquone/proguanil, Doxycycline and Mefloquine.

PMID- 20144810
TI  - [In ischemic disease, is the anterior ST segment elevation a synonym for anterior
      left ventricular acute myocardial infarction?].

PMID- 20144811
TI  - [Complex visual hallucinations in a patient with visual impairment (Charles
      Bonnet syndrome)].

PMID- 20144812
TI  - [Myelopathy in HIV and HTLV-2 coinfected patient].

PMID- 20144813
TI  - [Fatal sweet with pulmonary involvement].

PMID- 20144814
TI  - [Early mortality in the intensive care unit].

PMID- 20144815
TI  - [Assessment of a reconciliation and information programme for heart transplant
      patients].
AB  - INTRODUCTION: The objective is to assess a pharmaceutical care programme for
      heart transplant patients upon patient admission and discharge. MATERIAL AND
      METHODS: Observational study of heart transplant patients, performed during the
      first quarter of 2007. Upon admission, the patient was interviewed regarding home
      treatments, adherence, allergies and adverse effects, and his/her prescriptions
      were compared with the last discharge report (drug reconciliation). At time of
      discharge, treatment was checked against the last hospital prescription
      (reconciliation) and an informative report was drawn up and personally delivered
      to the patient. Subsequently, a satisfaction questionnaire was carried out by
      telephone. Drug-related problems were recorded using Atefarm software. RESULTS:
      The programme was applied to 24 patients upon admission and 23 upon discharge. No
      drug interactions were detected. Treatment adherence was higher than 90%. 37.5%
      of patients informed of an adverse reaction. Medication-related problems were
      identified in 16 patients (45.7%) for 6.6% of medications, most of which (38%)
      were for infection prophylaxis; medication omission was the most frequently
      detected error. Positive evaluation of the information that was received was
      higher than 90%. CONCLUSIONS: Pharmacotherapeutic follow-up upon admission and
      discharge resolves and prevents problems while improving patient information and
      satisfaction. Limitations on personnel prevent the population's requests from
      being met.

PMID- 20144816
TI  - [Pharmaceutical intervention with parenteral nutrition].
AB  - OBJECTIVE: Description and analysis of pharmaceutical interventions for patients
      with parenteral nutrition and an assessment of the degree of acceptance. METHOD:
      Prospective six-month study. Design of a data collection sheet (with personal
      data, the indication for parenteral nutrition, hospital area, nutrition type,
      time and type of intervention, type of notification, acceptance) for recording
      interventions carried out based on normal activities: complete review of
      pharmacotherapy and clinical history. RESULTS: A total of 265 interventions were
      carried out during the study period (1.5 interventions/day) with a mean of 2.1
      interventions/patient. The overall degree of acceptance was 83.77%; significant
      differences were found between type of communication for the intervention (oral
      and/or written) and the degree of acceptance. CONCLUSIONS: Adding a pharmacist to
      the care team permits direct intervention in partnership with the doctor, and it
      is an effective method for preventing and resolving the complications, generally
      metabolic, that are associated with parenteral nutrition. Using this process for
      resolving medication-related problems in hospitalised patients, principally in
      surgical areas, is an addition to the pharmacist's activities in the area of
      nutritional support.

PMID- 20144817
TI  - Role of health-related quality of life measurements in the design of drug
      clinical trials.
AB  - OBJECTIVE: Health-related quality of life (HRQL) measurements enable us to take
      patient perception into account when evaluating treatment outcomes from clinical
      trials (CTs). The purpose of this study was to evaluate the use of HRQL
      questionnaires as a measurement of efficacy in CT design. METHODS: A duplicate
      systematic review of the CTs examined by a Clinical Research Ethics Committee
      between 1995 and 2006 was performed to check for use of HRQL. We gathered data
      concerning general aspects including medical specialty, drugs evaluated,
      methodological quality and inclusion of economic variables. For CTs including
      HRQL measurements, we analysed the type of questionnaire in use. Where there were
      no HRQL measurements, we analysed the methodological possibilities for including
      them, and the relevance of their absence. RESULTS: A total of 242 CTs were
      analysed; 69 (28.5%) included HRQL measurements, and 10 CTs (4.1%) used them as a
      primary endpoint. Only 22 CTs used more than one questionnaire. Data analysis by
      therapeutic area showed that HRQL was most commonly studied in the fields of
      rheumatology, urology, psychiatry and oncology. Only 33 CTs included economic
      variables. CONCLUSIONS: Measurements based on clinical parameters are the most
      commonly used means of measuring efficacy. Only a small percentage of CTs take
      the patient's perception of his/her health into account, despite the increasing
      importance given to this parameter. Including HRQL questionnaires in CTs design
      is still far from common.

PMID- 20144818
TI  - [Effect of pamidronate infusion time on renal function in patients with multiple
      myeloma].
AB  - INTRODUCTION: Administration of biphosphonates in patients with renal failure
      requires a dosage adjustment. OBJECTIVES: Analyse renal function evolution in
      multiple myeloma patients after reducing infusion time for 90 mg pamidronate by 2
      h. METHODS: In 2007, a retrospective study was carried out on all patients who
      presented multiple myeloma and bone metastasis treated with pamidronate
      administered every 4 h. Following a review of the literature, a protocol for
      administering pamidronate every 2 h was created in partnership with Haematology,
      and a specific dose reduction framework was established for patients with
      baseline renal failure. Additionally, a prospective follow-up study of those
      patients' renal function was completed to analyse its evolution after the change
      in infusion time. RESULTS: A total of six patients received 90 mg pamidronate
      every 4 h. 33.32% of the patients (2/6) presented baseline renal insufficiency,
      and therefore needed to have the pamidronate dose adjusted according to the new
      protocol. Subsequently, all of them received the treatment every 2 h, and one
      patient (16.6%) experienced altered renal function after two treatment cycles.
      DISCUSSION: Reducing administration time for pamidronate from four to 2 h did not
      lead to significant variations in patients' renal function. This therapeutic
      practice can improve patients' quality of life by shortening their hospital stay
      without aggravating their renal function.

PMID- 20144819
TI  - [Measuring linezolid in biological fluids using high-efficiency liquid
      chromatography].
AB  - OBJECTIVE: Evaluation of an analytic method for determining linezolid
      concentrations in biological fluids including plasma, vitreous humour and
      cerebrospinal fluid using high-efficiency liquid chromatography and subsequent
      ultraviolet detection. METHOD: The method was validated by studying the following
      parameters: accuracy, precision, sensitivity, linearity and recovery. The drug
      was extracted from the biological matrix by means of a protein precipitation with
      perchloric acid. Chromatographic separation was performed by eluting linezolid
      with a mobile phase consisting of 80% K2HPO4 buffer solution (15 mM; pH=5) and
      20% acetonitrile, and a stationary phase, NOVAPAK C18 150x3.9 mm with precolumn.
      The wavelength reading was 254 nm and the working flow rate was 1 ml/min.
      RESULTS: We obtained values with accuracies between 94.4 and 106.1%, and
      precisions between 0.88-6% and 3.7-5.6% for intra-and inter-day variability,
      respectively. Recovery obtained after analysing the plasma samples was at 93%.
      The method showed itself to be linear for the concentration levels under study.
      DISCUSSION: The method's behaviour can be described as linear, precise and
      accurate. Furthermore, the method is fast, sensitive, and inexpensive. It is
      useful for determining linezolid concentrations in multiple biological matrices.
      It can also be used as a basis for further clinical pharmacokinetic studies.

PMID- 20144820
TI  - [Resistance to aspirin: prevalence, mechanisms of action and association with
      thromboembolic events. A narrative review].
AB  - OBJECTIVES: The purpose of this study is to review the prevalence of aspirin
      resistance in patients with a high risk of cardiovascular events, and secondly,
      to investigate its epidemiology and mechanism of action, and the clinical
      consequences it can provoke. MATERIAL AND METHODS: A search was run on PubMed,
      EMBASE and Reviews Database for English or Spanish articles on aspirin resistance
      published up to November 2008. Additional studies were obtained by searching the
      reference lists in the selected articles for articles relevant to our secondary
      objectives. RESULTS: Aspirin resistance is described as affecting 0 to 57% of the
      population, and is related to a decreased protective effect against strokes and
      cardiovascular events. Many modifiable and unmodifiable factors can affect the
      efficacy of antiplatelet drugs. Possible strategies for overcoming this decreased
      antiaggregant effect include increasing the aspirin dosage or dual therapy with
      another antiplatelet agent. CONCLUSIONS: Lack of response to aspirin decreases
      its protective effects. However, lack of a standard definition for aspirin
      resistance, the absence of diagnostic reference methods to identify resistant
      patients, and the different mechanisms of action involved in platelet aggregation
      call the clinical importance of this fact into question. Additional well-designed
      studies are needed to detect patients with real resistance in order to have more
      effective prevention of cardiovascular morbidity and mortality.

PMID- 20144821
TI  - [Mifepristone as a treatment alternative to chronic serous chorioretinopathy].

PMID- 20144822
TI  - [Renal failure due to simvastatin-induced rhabdomyolysis in a patient with
      subclinical hypothyroidism].

PMID- 20144823
TI  - [Botulism antitoxin treatment in two cases of foodborne botulism].

PMID- 20144824
TI  - [Topical cidofovir as a treatment for plantar warts].

PMID- 20144825
TI  - [Type B insulin resistance syndrome].

PMID- 20144826
TI  - Moving through imagined space: Mentally simulating locomotion during spatial
      description reading.
AB  - Readers mentally simulate the perceptual and motoric elements related through
      text. Sound is one perceptual characteristic of these embodied simulations that
      has received little attention. Two experiments tested whether movement sounds
      (walking vs. running) or metronome pulses (fast vs. slow) would modulate reading
      speed and memory for two different types of spatial descriptions, route and
      survey. Route descriptions describe environments from a first-person, ground
      level perspective whereas survey descriptions use an aerial overview perspective.
      Experiment 1 demonstrated that route description readers altered their reading
      speed in correspondence with both movement and metronome sounds, progressing
      through descriptions faster when hearing fast-paced versus slow-paced sounds.
      When reading survey descriptions, however, readers only modulated their reading
      speed while listening to metronome pulses. Those who showed the greatest reading
      time effects with the route description and footstep sounds also showed
      difficulty solving inferences from the survey perspective. Experiment 2
      demonstrated that movement sounds influenced perceptions of distance traveled
      such that estimates of environmental scale increased after listening to running
      versus walking sounds. Taken together these results demonstrate that route
      description readers mentally simulate a journey through a described world, and
      these simulations and the resulting spatial memories can be guided by auditory
      information.

PMID- 20144827
TI  - Acetylation and characterization of spruce (Picea abies) galactoglucomannans.
AB  - Acetylated galactoglucomannans (GGMs) are the main hemicellulose type in most
      softwood species and can be utilized as, for example, bioactive polymers,
      hydrocolloids, papermaking chemicals, or coating polymers. Acetylation of spruce
      GGM using acetic anhydride with pyridine as catalyst under different conditions
      was conducted to obtain different degrees of acetylation on a laboratory scale,
      whereas, as a classic method, it can be potentially transferred to the industrial
      scale. The effects of the amount of catalyst and acetic anhydride, reaction time,
      temperature and pretreatment by acetic acid were investigated. A fully acetylated
      product was obtained by refluxing GGM for two hours. The structures of the
      acetylated GGMs were determined by SEC-MALLS/RI, (1)H and (13)C NMR and FTIR
      spectroscopy. NMR studies also indicated migration of acetyl groups from O-2 or O
      3 to O-6 after a heating treatment in a water bath. The thermal stability of the
      products was investigated by DSC-TGA.

PMID- 20144828
TI  - Infants use rational decision criteria for choosing among models of their input.
AB  - Previous work demonstrated that 9-month-olds who were familiarized with 3
      syllable strings consistent with both a broader (AAB or ABA) and narrower (AAdi
      or AdiA) generalization made only the latter. Because the narrower generalization
      is a subset of the broader one, any example that is consistent with the broader
      generalization but not the narrower one should allow a rational learner to select
      the broader generalization. The current experiment asked whether infants show
      evidence of being such learners. Infants who heard the stimuli that previously
      led to the narrower generalization plus three counterexamples mixed into the last
      five stimuli made the broader generalization at test. A control condition ruled
      out the possibility that infants based their generalization on the last five
      familiarization stimuli. The new findings suggest that infants effectively
      consider multiple competing models for their input and use rational decision
      criteria for selecting among these models.

PMID- 20144829
TI  - Preparation of SrAl2O4:Eu(2+), Dy(3+) fibers by electrospinning combined with sol
      gel process.
AB  - One-dimensional SrAl(2)O(4):Eu(2+), Dy(3+) fibers were fabricated by a simple
      electrospinning combined with sol-gel process. X-ray diffraction, Fourier
      transform infrared spectroscopy, scanning electron microscopy, transmission
      electron microscopy and photoluminescence were used to characterize the fibers.
      The results show that the phase structure of SrAl(2)O(4):Eu(2+), Dy(3+) belongs
      to a monoclinic one, the composite fibers and fibers calcined at high temperature
      remain the original one-dimensional texture, and the SrAl(2)O(4):Eu(2+), Dy(3+)
      was a green emission.

PMID- 20144830
TI  - Micro-nano hierarchically structured nylon 6,6 surfaces with unique wettability.
AB  - A micro-nano hierarchically structured nylon 6,6 surface was easily fabricated by
      phase separation. Nylon 6,6 plate was swelled by formic acid and then immersed in
      a coagulate bath to precipitate. Micro particles with nano protrusions were
      generated and linked together covering over the surface. After dried up, the as
      formed surface showed superhydrophilic ability. Inspired by lotus only employing
      2-tier structure and ordinary plant wax to maintain superhydrophobicity, paraffin
      wax, a low surface energy material, was used to modify the hierarchically
      structured nylon 6,6 surface. The resultant surface had water contact angle (CA)
      of 155.2+/-1.3 degrees and a low sliding angle. The whole process was carried on
      under ambient condition and only need a few minutes.

PMID- 20144831
TI  - PDMS spreading morphological patterns on substrates of different hydrophilicity
      in air vacuum and water.
AB  - In paper has been to investigate the morphological patterns and kinetics of PDMS
      spreading on silicon wafer using combination of techniques like ellipsometry,
      atomic force microscope (AFM), scanning electron microscope (SEM) and optical
      microscopy. A macroscopic silicone oil drops as well as PDMS water based
      emulsions were studied after deposition on a flat surface of silicon wafer in
      air, water and vacuum. Our own measurements using an imaging ellipsometer, which
      also clearly shows the presence of a precursor film. The diffusion constant of
      this film, measured with a 60,000 cS PDMS sample spreading on a hydrophilic
      silicon wafer is D(f)=1.4x10(-11) m(2)/s. Regardless of their size, density and
      method of deposition, droplets on both types of wafer (hydrophilic and
      hydrophobic) flatten out over a period of many hours, up to 3 days. During this
      process neighbouring droplets may coalesce, but there is strong evidence that
      some of the PDMS from the droplets migrates into a thin, continuous film that
      covers the surface in between droplets. The thin film appears to be ubiquitous if
      there has been any deposition of PDMS. However, this statement needs further
      verification. One question is whether the film forms immediately after forced
      drying, or whether in some or all cases it only forms by spreading from isolated
      droplets as they slowly flatten out.

PMID- 20144832
TI  - Bidisperse colloids: nanoparticles and microemulsions in coexistence.
AB  - Mixed 'hard-soft' colloidal systems have been generated in which the 'hard'
      components (80 nm diameter silica nanoparticles) coexist with a population of
      'soft' microemulsion droplets, both structures stabilised by the anionic
      surfactant sodium bis(ethylhexyl)sulfosuccinate (AOT) with toluene as solvent.
      The addition of water to swell the inverse micelles to form microemulsion
      droplets appears to increase attractive interactions between the silica particles
      (determined by DLS), possibly due to adsorption of some water at the silica
      toluene interface; however, long-term stability of the dispersions is maintained.
      Small-angle neutron scattering was used to examine the structures present in
      these new colloidal systems.

PMID- 20144833
TI  - Variations in mechanical and thermal properties of mesoporous alumina thin films
      due to porosity and ordered pore structure.
AB  - Ordered mesoporous aluminum oxide films with porosity ranging between 5% and 37%
      were synthesized by evaporation-induced self-assembly (EISA) using surfactant
      templating. To investigate the effects of mesoporous structure on thermal
      properties, changes in pore structure including pore size, pore distribution, and
      porosity were monitored as a function of surfactant concentration (Pluronic P
      123, poly(ethylene oxide)(20)-poly(propylene oxide)(70)-poly(ethylene
      oxide)(20)). The ordered mesoporous alumina films were then examined to determine
      how their morphology influences their thermal properties. These alumina films had
      a body-centered cubic pore structure or a random-oriented pore structure,
      depending on the surfactant concentration used, and superior thermal properties
      were obtained by controlling porosity and pore structure. Therefore, the ordered
      mesoporous alumina films synthesized in this study can be used as high
      temperature thermo-isolating materials.

PMID- 20144834
TI  - Surface force measurements at the basal planes of ordered kaolinite particles.
AB  - An experimental procedure is presented to order kaolinite particles on substrates
      for interrogation of the two basal plane surfaces by atomic force microscopy.
      Surface force measurements were performed between a silicon nitride tip and each
      of the two faces (silica tetrahedral face and alumina octahedral face) of
      kaolinite in 1 mM KCl solution at pH 4, 5, 6, 8 and 10, using atomic force
      microscopy. The colloidal force measurements reveal that the silica tetrahedral
      face of kaolinite is negatively charged at pH>4, whereas the alumina octahedral
      face of kaolinite is positively charged at pH<6, and negatively charged at pH>8.
      Such measurements have not been reported previously and the results suggest that
      the iso-electric point of the silica tetrahedral face is at pH<4, and that the
      iso-electric point of the alumina octahedral face lies between pH 6 and 8. These
      results contradict the generally accepted view that basal plane surfaces of
      kaolinite carry a permanent negative charge due to minor substitution of Al(3+)
      for Si(4+) in the silica tetrahedral layer, and suggest some surface charge
      dependency of the two faces with respect to solution pH. With this new
      information it may be possible to further explain the electrokinetic behavior of
      kaolinite particles, and their interactions in aqueous suspensions.

PMID- 20144835
TI  - Benthic macrofaunal community condition in the southern California bight, 1994
      2003.
AB  - To assess benthic macrofaunal community condition in Southern California, 838
      sites were sampled using spatially random designs in 1994, 1998, or 2003. Benthic
      community condition was assessed on a four-category scale and the area in each
      category estimated. Overall, benthic macrofauna in Southern California were in
      good condition during 2003, with 98% of the area in reference condition or
      deviating only marginally. There was no evidence of disturbance near Channel
      Islands or small wastewater discharges, and virtually none on the mainland shelf.
      In contrast, bay and estuary macrofaunal communities were more frequently
      disturbed with nearly 13% of the area supporting disturbed benthos. The condition
      of the mainland shelf did not change substantially over the 9-year period, with
      1.6-2.8% of the area in poor benthic condition. Southern California benthic
      condition evaluations may be improved by extending the depth and salinity ranges
      of assessment tools, and improving trend detection methods.

PMID- 20144836
TI  - Produced water extracts from North Sea oil production platforms result in
      cellular oxidative stress in a rainbow trout in vitro bioassay.
AB  - Produced water (PW) discharged from offshore oil industry contains chemicals
      known to contribute to different mechanisms of toxicity. The present study aimed
      to investigate oxidative stress and cytotoxicity in rainbow trout primary
      hepatocytes exposed to the water soluble and particulate organic fraction of PW
      from 10 different North Sea oil production platforms. The PW fractions caused a
      concentration-dependent increase in reactive oxygen species (ROS) after 1h
      exposure, as well as changes in levels of total glutathione (tGSH) and
      cytotoxicity after 96 h. Interestingly, the water soluble organic compounds of PW
      were major contributors to oxidative stress and cytotoxicity, and effects was not
      correlated to the content of total oil in PW. Bioassay effects were only observed
      at high PW concentrations (3-fold concentrated), indicating that bioaccumulation
      needs to occur to cause similar short term toxic effects in wild fish.

PMID- 20144837
TI  - Comparative efficacy of BAC-derived recombinant SB-1 vaccine and the parent wild
      type strain in preventing replication, shedding and disease induced by virulent
      Marek's disease virus.
AB  - A widely used vaccine against Marek's disease (MD) in poultry is the virus SB-1,
      which is antigenically-related to the causative agent, Marek's disease
      herpesvirus. We recently cloned the SB-1 genome as an infectious bacterial
      artificial chromosome, BAC, (pSB-1). The protective efficacies and replication
      kinetics of pSB-1 and the parent strain (SB-1) were compared in an experimental
      model of MD induced by a virulent strain, RB-1B. Although vaccine virus
      replication and shedding was lower for pSB-1 than for SB-1, both vaccines reduced
      replication and shedding of RB-1B, and were equally effective in protecting
      chickens against MD. With the cloning of pSB-1, we have now generated full length
      genomic clones of MD vaccine virus strains belonging to each of the three
      serotypes. Vaccine viruses derived from each of these clones demonstrated
      protective efficacies at levels similar to those produced by the respective
      parent viruses, demonstrating their suitability to be used as vaccine candidates.

PMID- 20144838
TI  - Earthworm-microorganism interactions: a strategy to stabilize domestic wastewater
      sludge.
AB  - The performance of a conventional biofilter (BF) and a vermifilter containing the
      earthworm, Eisenia foetida, (VF) for the treatment of domestic wastewater sludge
      were compared with the earthworm-microorganism interaction mechanisms involved in
      sludge stabilization. The results revealed that the presence of earthworms in the
      VF led to significant stabilization of the sludge by enhancing the reduction in
      volatile suspended solids (VSS) by 25.1%. Digestion by earthworms and the
      earthworm-microorganism interactions were responsible for 54% and 46% of this
      increase, respectively. Specifically, earthworms in the VF were capable of
      transforming insoluble organic materials to a soluble form and then selectively
      digesting the sludge particles of 10-200 microm to finer particles of 0-2 microm,
      which led to the further degradation of organic materials by the microorganisms
      in the reactor. Additionally, denaturing gradient gel electrophoresis (DGGE)
      profiles showed that there was an intensified bacterial diversity in the
      vermifilter due to the presence of earthworms, especially in response to the
      nutrients in their casts.

PMID- 20144839
TI  - Peak flux performance and microbial removal by selected membrane bioreactor
      systems.
AB  - A pilot study was conducted over a period of 18 months at the Point Loma
      Wastewater Treatment Plant (PLWWTP) in San Diego, CA to evaluate the operational
      and water quality performance of six selected membrane bioreactor (MBR) systems
      at average and peak flux operation. Each of these systems was operated at peak
      flux for 4 h a day for six consecutive days to assess peak flux performance.
      Virus seeding studies were also conducted during peak flux operation to assess
      the capability of these systems to reject MS-2 coliphage. When operating at
      steady state, these MBR systems achieved an effluent BOD concentration of <2 mg/L
      and a turbidity of <0.1 NTU. Peak flux for the MBR systems ranged from 56 to 76
      L/m2/h (liters per square meter per hour) with peaking factors in the range of
      1.5-3.2. When switching from average to peak flux operation, a reversible drop of
      22-32% in temperature-corrected permeability was observed for all submerged MBR
      systems. The percent drop in permeability increased as MLSS concentration in the
      membrane tank increased from 11,100 mg/L to 15,300 mg/L and was observed to be
      highest for the system operating at highest MLSS concentration. Such trends were
      not observed with an external MBR system. Each MBR system was able to sustain a 4
      h-a-day peak flow for six consecutive days with only moderate membrane fouling.
      The membrane fouling was quantified by measuring the drop in temperature
      corrected permeability. This drop ranged from 13 to 33% over six days for
      different submerged MBR systems. The MBR systems achieved microbial removal in
      the range of 5.8-6.9 logs for total coliform bacteria, >5.5 to >6.0 logs for
      fecal coliform bacteria and 2.6 to >3.4 logs for indigenous MS-2 coliphages. When
      operating at peak flux, seeded MS-2 coliphage removal ranged from 1.0 to 4.4
      logs, respectively. The higher log removal values (LRVs) for indigenous MS-2
      coliphage among different MBR systems were probably the result of particle
      association of indigenous coliphage. Differences in membrane pore size (0.04-0.2
      microm) amongst the MBR systems evaluated did not have a substantial impact on
      indigenous MS-2 coliphage removal, but seeded MS-2 coliphage removal varied among
      the different MBR systems.

PMID- 20144840
TI  - Surprising duplex stabilisation upon mismatch introduction within triply modified
      duplexes.
AB  - Three different modified phosphoramidite nucleoside building blocks equipped with
      additional protected imidazole, masked alcohol and masked carboxylate
      functionality are synthesized and incorporated into oligonucleotides. Based on
      the serine-protease active site model, doubly and triply modified duplexes are
      created and tested for stability. Analysis of different spatial distributions of
      the extra functionalities shows that careful positioning can even overcome duplex
      destabilisation caused by the introduction of mismatches.

PMID- 20144841
TI  - Oxidative degradation of 1,5-naphthalenedisulfonic acid in aqueous solutions by
      UV-photolysis in the absence and presence of H2O2.
AB  - Sulfonated aromatic pollutants such as 1,5-naphthalenedisulfonic acid (NDS or
      Armstrong's acid) are persistent compounds and thus resist environmental
      breakdown and microbial treatment. This study investigated the photo-oxidative
      degradation of such a persistent polar pollutant in the absence and presence of
      H2O2. The degradation of aqueous NDS solutions by photolysis was found to be
      efficient only in the presence of H2O2. The combination of UV irradiation and
      H2O2 leads to progressive degradation of NDS, which is converted into new, more
      biodegradable and non-toxic species.

PMID- 20144842
TI  - Ovarian cancer creates a suppressive microenvironment to escape immune
      elimination.
AB  - BACKGROUND: Considering the high mortality rate of ovarian cancer due to the
      absence of curative treatment in advanced stage or at recurrence, new therapeutic
      strategies are urgently needed. Immunotherapy is one of these strategies that
      yielded promising results in fundamental and animal research in the past years.
      However, implementation in clinical practice remains poor. The aim of this review
      is to gain insight into the mechanisms of interaction between ovarian cancer and
      the immune system in order to develop better immunotherapeutic strategies.
      METHODS: We searched the published literature for studies focusing on
      interactions between ovarian cancer and the immune system, with emphasis on
      outcome data in order to create a knowledge base that is well grounded in
      clinical reality. RESULTS: The immunological response against cancer is a
      critical balance between immune-activating and immune-suppressing mechanisms.
      Besides the immune-activating tumor infiltrating lymphocytes (TILs), immune
      suppressive regulatory T-cells (Tregs), tolerance-inducing plasmacytoid dendritic
      cells (pDCs), B7-H4+ macrophages, immune-suppressive cytokines such as IL10 and
      TGF-beta are also found in the tumor environment. Myeloid-derived suppressive
      cells (MDSCs) are recently found to have a significant role in immune suppression
      in ovarian cancer in murine studies. Furthermore, vascular endothelial growth
      factor (VEGF) is also known to have an immune-suppressing role besides its
      angiogenic role. All those concerted mechanisms result in the creation of an
      environment where the cancer is invincible and can grow unhampered. CONCLUSION:
      Further knowledge of the mechanisms involved is needed to develop better
      strategies and improve the clinical applicability of immunotherapy. Effective
      immunotherapy must combine immune-activating strategies with elimination of
      immune-suppressing mechanisms. We believe that tilting the balance from an immune
      suppressive to an immune-active environment may have an enormous impact on the
      disease.

PMID- 20144843
TI  - Letter to the editor with comments on article by Cole and Muller entitled
      "Hyperglycosylated hCG in the management of quiescent and chemorefractory
      gestational trophoblastic diseases".

PMID- 20144844
TI  - Biodegradable magnetic-fluorescent magnetite/poly(dl-lactic acid-co-alpha,beta
      malic acid) composite nanoparticles for stem cell labeling.
AB  - Bifunctional superparamagnetic magnetite/poly(dl-lactic acid-co-alpha,beta-malic
      acid) composite nanoparticles (PLMA-MNPs) detectable by both magnetic resonance
      imaging (MRI) and fluorescence microscopy were synthesized by coating Fe(3)O(4)
      nanoparticles with biodegradable poly(dl-lactic acid-co-alpha,beta-malic acid)
      copolymer (PLMA) with covalently bound fluorescein isothiocyanate (FITC). The
      FITC modified PLMA-MNPs (FITC-PLMA-MNPs) have a hydrodynamic diameter of 100nm
      and an anionic surface. MTT assays of mouse macrophages, 3T3 fibroblasts and
      human mesenchymal stem cells (hMSCs) incubated with these nanoparticles indicated
      that these nanoparticles did not possess significant cytotoxicity. Furthermore,
      the osteogenic and adipogenic differentiations of the hMSCs were not influenced
      by the labeling process. As a result of the high R(2) (164.8mm(-1)s(-1)) and
      R(2)/R(1) ratio (32) of the FITC-PLMA-MNPs, the labeled hMSCs can be detected by
      a clinical 3T MRI scanner at an in vitro detection threshold of about 1200 cells.
      The green fluorescence associated with the FITC can be readily observed. Such
      nanoparticles can potentially be used as a T(2)-weighted contrast agent and
      fluorescent agent for stem cell labeling.

PMID- 20144845
TI  - The performance of a hemostatic agent based on oxidized regenerated cellulose-
      polyglactin 910 composite in a liver defect model in immunocompetent and athymic
      rats.
AB  - Many surgical methods and hemostatic agents can be used to achieve and maintain
      hemostasis in surgical fields. Numerous clinical situations exist where current
      treatment modalities are neither effective nor practical. Assessment of new
      hemostats primarily targets efficacy. However, the biocompatibility and healing
      properties associated with hemostats are crucial for regulatory approval and
      product acceptance. Standard biocompatibility and healing studies may not be
      appropriate for hemostats containing active biologics. Liver defects in NTac:NIH
      Whn (athymic) and Sprague Dawley Outbred (immunocompetent) rats were treated with
      Fibrin Pad (absorbable matrix containing human-derived biologics) or the matrix
      only. Defects were evaluated at 14 and 28 days post-implantation. As expected,
      Fibrin Pad in immunocompetent rats induced a cellular immune response.
      Unexpectedly, biologically significant decreases in healing, material absorption,
      and local fibrin degradation were also present. Evaluation of Fibrin Pad in
      immunocompetent animal models must consider potentially significant alterations
      in healing, material absorption, and local fibrin degradation, in addition to the
      expected immune response; none of which may be relevant when Fibrin Pad is used
      in the clinical setting. These considerations are essential when standard
      efficacy and biocompatibility studies assessing Fibrin Pad are submitted for
      regulatory consideration or utilized as pre-clinical translational studies.

PMID- 20144846
TI  - Anisotropic dynamic changes in the pore network structure, fluid diffusion and
      fluid flow in articular cartilage under compression.
AB  - A compression cell designed to fit inside an NMR spectrometer was used to
      investigate the in situ mechanical strain response, structural changes to the
      internal pore structure, and the diffusion and flow of interstitial water in full
      thickness cartilage samples as it was deforming dynamically under a constant
      compressive load (pressure). We distinguish between the hydrostatic pressure
      acting on the interstitial fluid and the pore pressure acting on the cartilage
      fibril network. Our results show that properties related to the pore matrix
      microstructure such as diffusion and hydraulic conductivity are strongly
      influenced by the hydrostatic pressure in the interstitial fluid of the
      dynamically deforming cartilage which differ significantly from the properties
      measured under static i.e. equilibrium loading conditions (when the hydrostatic
      pressure has relaxed back to zero). The magnitude of the hydrostatic fluid
      pressure also appears to affect the way cartilage's pore matrix changes during
      deformation with implications for the diffusion and flow-driven fluid transport
      through the deforming pore matrix. We also show strong evidence for a highly
      anisotropic pore structure and deformational dynamics that allows cartilage to
      deform without significantly altering the axial porosity of the matrix even at
      very large strains. The insensitivity of the axial porosity to compressive strain
      may be playing a critical function in directing the flow of pressurized
      interstitial fluid in the compressed cartilage to the surface, to support the
      load, and provide a protective interfacial fluid film that 'weeps' out from the
      deforming tissue and thereby enhances the (elasto)hydrodynamic efficacy of
      sliding joints. Our results appear to show a close synergy between the structure
      of cartilage and both the hydrodynamic and boundary lubrication mechanisms.

PMID- 20144847
TI  - Dinuclear triphenylphosphinegold(I) sulfanylcarboxylates: Synthesis, structure
      and cytotoxic activity against cancer cell lines.
AB  - Compounds of the type [(AuPPh(3))(2)(xspa)]; H(2)xspa [x:p=3-phenyl-, f=3-(2
      furyl)-, t=3-(2-thienyl)-, -o-py=3-(2-pyridyl)-, Clp=3-(2-chlorophenyl)-, -o-mp=3
      (2-methoxyphenyl)-, -p-mp=3-(4-methoxyphenyl)-, -o-hp=3-(2-hydroxyphenyl)-, -p
      hp=3-(4-hydroxyphenyl)-, -diBr-o-hp=3-(3,5-dibromo-2-hydroxyphenyl)-; spa=2
      sulfanyl propenoato] were synthesized and characterized by IR and NMR ((1)H,
      (13)C and (31)P) spectroscopy and by FAB mass spectrometry. The structures of
      [(AuPPh(3))(2)(Clpspa)], [(AuPPh(3))(2)(o-hpspa)], [(AuPPh(3))(2)(p-hpspa)].MeOH
      and [(AuPPh(3))(2)(diBr-o-hpspa)].2Me(2)CO show the dinuclear nature of the
      complexes with the two gold atoms, one of which is also O-bonded to an O atom of
      the carboxylate group, bonded to the S atom. The in vitro antitumor activities
      against the HeLa-229, A2780 and A2780cis cell lines were determined and the
      compounds were found to be highly effective, in particular against the A2780cis
      cell line, with eight of the nine compounds having IC(50) values better than that
      of cisplatin. This behavior is indicative of a high ability to circumvent the
      cellular resistance to this drug.

PMID- 20144848
TI  - Overexpression of c-myc induces epithelial mesenchymal transition in mammary
      epithelial cells.
AB  - The c-myc gene is frequently overexpressed in human breast cancer and its target
      genes are involved in tumorigenesis. Epithelial mesenchymal transitions (EMT),
      where cells undergo a developmental switch from a polarized epithelial phenotype
      to a highly motile mesenchymal phenotype, are associated with invasion and
      motility of cancer cells. Basal E-cadherin expression was down-regulated in c-myc
      overexpressing MCF10A (c-myc-MCF10A) cells compared to GFP-overexpressing MCF10A
      (GFP-MCF10A) cells, while N-cadherin was distinctly increased in c-myc-MCF10A
      cells. Given that glycogen synthase kinase-3beta (GSK-3beta) and the snail axis
      have key roles in E-cadherin deregulation during EMT, we investigated the role of
      GSK-3beta/snail signaling pathways in the induction of EMT by c-myc
      overexpression. In contrast to GFP-MCF10A cells, both the transcriptional
      activity and the ubiquitination-dependent protein stability of snail were
      enhanced in c-myc-MCF10A cells, and this was reversed by GSK-3beta
      overexpression. We also found that c-myc overexpression inhibits GSK-3beta
      activity through activation of extracellular signal-regulated kinase (ERK).
      Inhibition of ERK by dominant negative mutant transfection or chemical inhibitor
      significantly suppressed snail gene transcription. These results suggest that c
      myc overexpression during transformation of mammary epithelial cells (MEC) is
      involved in EMTs via ERK-dependent GSK-3beta inactivation and subsequent snail
      activation.

PMID- 20144850
TI  - Lentiviral shRNA screen of human kinases identifies PLK1 as a potential
      therapeutic target for osteosarcoma.
AB  - We describe an optimized systematic screen of known kinases using osteosarcoma
      cell lines (KHOS and U-2OS) and a lentiviral-based short hairpin RNA (shRNA)
      human kinase library. CellTiter 96(R)AQueous One Solution Cell Proliferation
      Assay was used to measure cell growth and survival. We identified several
      kinases, including human polo-like kinase (PLK1), which inhibit cell growth and
      induce apoptosis in osteosarcoma cells when knocked down. cDNA rescue and
      synthetic siRNA assays confirm that the observed phenotypic changes result from
      the loss of PLK1 gene expression. Furthermore, a small molecule inhibitor to PLK1
      inhibited osteosarcoma cell growth and induced apoptosis. Western blot analysis
      confirmed that PLK1 is highly expressed and activated in several osteosarcoma
      cell lines as well as in resected tumor samples. Immunohistochemistry analysis
      showed that patients with high PLK1 tumor expression levels correlated with
      significantly shorter survival than patients with lower levels of tumor PLK1
      expression. These results demonstrate the capability and feasibility of a high
      throughput screen with a large collection of lentiviral kinases and its
      effectiveness in identifying potential drug targets. The development of more
      potent inhibitors that target PLK1 may open doors to a new range of anti-cancer
      strategies in osteosarcoma.

PMID- 20144849
TI  - Captopril and S-nitrosocaptopril as potent radiosensitizers: Comparative study
      and underlying mechanisms.
AB  - In an effort to improve the issue of radiotherapy treatments, we tested whether S
      nitrosocaptopril, a molecule combining a NO donor and an angiotensin converting
      enzyme inhibitor (ACE inhibitor), could temporarily improve the hemodynamic
      status of experimental tumors. We monitored the effect of S-nitrosocaptopril in
      TLT tumors using non rinvasive magnetic resonance techniques. We identified a
      time window during which tumor oxygenation was improved, as a result of a
      combined effect on tumor blood flow and oxygen consumption. Consequently, the
      administration of S-nitrosocaptopril contributed to the increase in efficacy of
      radiation therapy, an effect that was not observed with captopril alone.

PMID- 20144851
TI  - Enriched fluoride sorption using alumina/chitosan composite.
AB  - Alumina possesses an appreciable defluoridation capacity (DC) of 1566 mg F(-)/kg.
      In order to improve its DC, it is aimed to prepare alumina polymeric composites
      using the chitosan. Alumina/chitosan (AlCs) composite was prepared by
      incorporating alumina particles in the chitosan polymeric matrix, which can be
      made into any desired form viz., beads, candles and membranes. AlCs composite
      displayed a maximum DC of 3809 mg F(-)/kg than the alumina and chitosan (52 mg F(
      )/kg). The fluoride removal studies were carried out in batch mode to optimize
      the equilibrium parameters viz., contact time, pH, co-anions and temperature. The
      equilibrium data was fitted with Freundlich and Langmuir isotherms to find the
      best fit for the sorption process. The calculated values of thermodynamic
      parameters indicate the nature of sorption. The surface characterisation of the
      sorbent was performed by FTIR, AFM and SEM with EDAX analysis. A possible
      mechanism of fluoride sorption by AlCs composite has been proposed. Suitability
      of AlCs composite at field conditions was tested with a field sample taken from a
      nearby fluoride-endemic village. This work provides a potential platform for the
      development of defluoridation technology.

PMID- 20144852
TI  - [Induced hypothermia in the term newborn infant after perinatal asphyxia].

PMID- 20144853
TI  - Regulation of plasmacytoid dendritic cell development.
AB  - Plasmacytoid dendritic cells (PDC) represent a distinct immune cell type
      specialized in direct virus recognition and rapid secretion of type I interferon.
      The origin and lineage affiliation of PDC have been controversial, partly because
      PDC show features of both lymphocytes and dendritic cells (DC). Recent studies
      helped elucidate the cellular and molecular basis of PDC development. In
      particular, the common developmental origin and genetic similarity of PDC and
      classical antigen-presenting DC have been established. In addition, E protein
      transcription factor E2-2 was shown to control lineage commitment and gene
      expression program of PDC. Because E proteins are essential regulators of
      lymphocyte development, E2-2 activity may underlie the distinct 'lymphoid'
      features of PDC.

PMID- 20144854
TI  - Transcription control of early B cell differentiation.
AB  - Differentiation of B lymphocytes involves the step-wise acquisition of a
      specialized phenotype that depends on the expression of lineage-specific genes
      and the repression of genes characteristic of multipotent progenitors and
      alternate lineages. The early steps of B lineage specification and commitment
      are, partly, controlled by the well-characterized transcription factors Ikaros,
      Pu.1, E2A, early B cell factor-1, and Pax5 that act in a complex regulatory
      network. However, our understanding of B cell differentiation is far from
      complete. Recent work has shed light on the mechanisms by which transcription
      factors implement cell type-specific gene expression patterns and epigenetic
      changes in chromatin that allow for B lineage specification and commitment.

PMID- 20144855
TI  - Role of basophils in the initiation of Th2 responses.
AB  - Long appreciated for their role as Type-2 effector cells, basophils have recently
      come into the spotlight for their role in the initiation of Type-2 immunity. Via
      an assortment of different activation pathways, basophils produce cytokines such
      as IL-4 that promote Th2 differentiation. Furthermore, recent studies using
      different experimental systems have shown that basophils can act as antigen
      presenting cells both in vitro and in vivo. In addition, basophils shape the Type
      2 immune response by guiding antibody production and the memory response.

PMID- 20144856
TI  - Macrophages, innate immunity and cancer: balance, tolerance, and diversity.
AB  - Smouldering inflammation is a component of the tumor microenvironment and
      represents the 7(th) hallmark of cancer. Tumor-associated macrophages (TAM) have
      served as a paradigm for cancer promoting inflammation. Tumor-associated
      macrophages orchestrate various aspects of cancer, including: diversion and
      skewing of adaptive responses; cell growth; angiogenesis; matrix deposition and
      remodelling; the construction of a metastatic niche and actual metastasis;
      response to hormones and chemotherapeutic agents. T and B cells or cancer cell
      derived signals orchestrate the functional reprogramming of TAM. In general TAM
      acquire M2-like properties and resemble 'tolerant' macrophages, though there is
      diversity in pathways and phenotypes in different tumors. TAM can also express
      antitumor activity. Thus, in response to microenvironmental signals, TAM can
      exert dual influence on tumor growth and progression.

PMID- 20144858
TI  - The clinical utility of long-term humidification therapy in chronic airway
      disease.
AB  - AIM: Persistent airway inflammation with mucus retention in patients with chronic
      airway disorders such as COPD and bronchiectasis may lead to frequent
      exacerbations, reduced lung function and poor quality of life. This study
      investigates if long-term humidification therapy with high flow fully humidified
      air at 37 degrees C through nasal cannulae can improve these clinical outcomes in
      this group of patients. METHOD: 108 patients diagnosed with COPD or
      bronchiectasis were randomised to daily humidification therapy or usual care for
      12 months over which exacerbations were recorded. Lung function, quality of life,
      exercise capacity, and measures of airway inflammation were also recorded at
      baseline, 3 and 12 months. RESULTS: Patients on long-term humidification therapy
      had significantly fewer exacerbation days (18.2 versus 33.5 days; p = 0.045),
      increased time to first exacerbation (median 52 versus 27 days; p = 0.0495) and
      reduced exacerbation frequency (2.97/patient/year versus 3.63/patient/year; p =
      0.067) compared with usual care. Quality of life scores and lung function
      improved significantly with humidification therapy compared with usual care at 3
      and 12 months. CONCLUSION: Long-term humidification therapy significantly reduced
      exacerbation days, increased time to first exacerbation, improved lung function
      and quality of life in patients with COPD and bronchiectasis. Clinical trial
      registered with www.actr.org.au; Number ACTRN2605000623695.

PMID- 20144857
TI  - Immunity to stemness genes in human cancer.
AB  - A growing body of data points to not only intraclonal heterogeneity and hierarchy
      of growth potential, but also plasticity of cellular differentiation within human
      tumors. Recent studies have also identified surprising overlap between pathways
      that regulate pluripotency in embryonal stem (ES) cells and oncogenesis. While
      there is a long history of targeting embryonal tissues toward cancer vaccines,
      recent identification of crucial stemness pathways in ES cells as well as
      putative cancer stem cells (CSCs) provides novel opportunities for antigen
      specific targeted therapy. Here we discuss recent insights into the capacity of
      the immune system to target these pathways. Immunologic targeting of pathways
      associated with stemness has implications for both immune regulation of tumor
      growth as well as regenerative therapies with embryonal stem cells.

PMID- 20144859
TI  - How much will it cost? Estimation of resource needs and availability for HIV
      prevention, treatment and care for people who inject drugs in Asia.
AB  - As countries in Asia strive to meet their universal access targets, harm
      reduction programmes are yet to be scaled up to reach effective levels of
      coverage. Resource tracking and estimation of resource needs and gaps is critical
      to inform the financing decisions of major donors of harm-reduction programmes in
      the region. This study aimed at estimating the financial resource needs and gaps
      for scaling-up harm reduction in the region, building on previous research
      conducted by the Independent Commission on AIDS in Asia. The overall resource
      need for achieving universal access in the target population in 2009 was US $0.5
      billion, with NSP and OST accounting for nearly 70% of the overall regional
      resource need. A significant resource gap, approximately 90%, of the resource
      need in 2009, was identified for harm reduction in the region, representing less
      than 2% of the overall global resource need to address AIDS. Additional resources
      will be required to support the introduction and scaling-up of integrated,
      comprehensive harm-reduction programmes that provide a full range of services to
      reduce HIV transmission among people who inject drugs.

PMID- 20144860
TI  - Hypoxia upregulates adhesion ability to peritoneum through a transforming growth
      factor-beta-dependent mechanism in diffuse-type gastric cancer cells.
AB  - Gastric cancer cells leaving the primary tumour are exposed to low oxygen levels
      in the peritoneal cavity; however, peritoneal metastatic phenotypes of hypoxic
      cancer cells remain unclear. We used 6 gastric cancer cell lines, including 3
      diffuse-type gastric cancer (DGC) and 3 non-DGC cell lines. Using adhesion assay,
      we examined the effect of hypoxic conditions on their ability to adhere to
      peritoneal components. The expression level of transforming growth factor-beta
      (TGF-beta) and integrins mRNA of cancer cells was examined using reverse
      transcriptase-polymerase chain reaction. We further examined the effect of anti
      integrin neutralising antibodies and a TGF-beta receptor inhibitor on the
      adhesion ability of hypoxic cancer cells. The binding ability of DGC cells was
      higher than that of non-DGC cells; it was significantly increased by hypoxic (1%
      O2) conditions compared to normoxic (21% O2) conditions. In contrast, no
      remarkable change in adhesion ability was observed in the non-DGC cells under
      normoxic and hypoxic conditions. Integrins and TGF-beta expression of hypoxic DGC
      cells was significantly higher than that of normoxic cells. TGF-beta increased
      the adhesion ability and alpha2-, alpha3- and alpha5-integrin expression of
      hypoxic DGC cells, whereas the TGF-beta receptor inhibitor decreased them.
      Neutralising antibodies against alpha2-, alpha3- and alpha5-integrin inhibited
      the adhesion ability of DGC cells. These findings suggested that hypoxic
      conditions promote the adhesion of DGC cells to the peritoneum. The upregulation
      of alpha2-, alpha3- and alpha5-integrin by TGF-beta under hypoxic conditions may
      be one of the mechanisms responsible for the high metastatic potential of hypoxic
      DGC cells to the peritoneum.

PMID- 20144861
TI  - Hydrogenotrophic denitrification in a packed bed reactor: effects of hydrogen-to
      water flow rate ratio.
AB  - Hydrogen dissolution and hydrogenotrophic denitrification performance were
      investigated in a lab-scale packed bed reactor (PBR) by varying the hydrogen flow
      rate and hydraulic retention time (HRT). The denitrification performance was
      enhanced by increasing the hydrogen flow rate and HRT as a result of high
      dissolved hydrogen concentration (0.39mg/L) and utilization efficiencies (79%).
      In this study, the hydrogen-to-water flow rate ratio (Q(g)/Q(w)) was found to be
      a new operating factor representing the two parameters of hydrogen flow rate and
      HRT. Hydrogen dissolution and denitrification efficiency were nonlinearly and
      linearly correlated with the Q(g)/Q(w), respectively. Based on its excellent
      linear correlation with denitrification efficiency, Q(g)/Q(w) should be greater
      than 2.3 to meet the WHO's guideline of nitrate nitrogen for drinking water. This
      study demonstrates that Q(g)/Q(w) is a simple and robust factor to optimize
      hydrogen-sparged bioreactors for hydrogenotrophic denitrification.

PMID- 20144862
TI  - Canola straw chemimechanical pulping for pulp and paper production.
AB  - Non-wood is one of the most important raw materials for pulp and paper production
      in several countries due to its abundance and cost-effectiveness. However, the
      pulping and papermaking characteristics of canola straw have rarely been
      investigated. The objective of this work was to determine the potential
      application of canola straw in the chemimechanical pulping (CMP) process. At
      first, the chemical composition and characteristics of canola straw were assessed
      and compared with those of other non-woods. Then, the CMP pulping of canola straw
      was conducted using different dosages of sodium sulfite and sodium hydroxide. The
      results showed that, by applying a mild chemical pretreatment, i.e., 4-12% (wt.)
      NaOH and 8-12% (wt.) Na(2)SO(3), in the CMP pulping of canola straw, the pulp
      brightness reached almost 40%ISO, and the strength properties were comparable to
      those of bagasse CMP and of wheat straw CMP. The impact of post-refining on the
      properties of canola straw CMP was also discussed in this work.

PMID- 20144863
TI  - A simple expression for the apparent reaction rate of large wood char
      gasification with steam.
AB  - A simple expression for the apparent reaction rate of large wood char
      gasification with steam is proposed. Large char samples were gasified under steam
      atmosphere using a thermo-balance reactor. The apparent reaction rate was
      expressed as the product of the intrinsic rate and the effective factor. The
      effective factor was modified to include the effect of change in char diameter
      and intrinsic reaction rate during the reaction. Assuming uniform conversion
      ratio throughout a particle, the simplified reaction scheme was divided into
      three stages. In the initial stage, the local conversion ratio increases without
      particle shrinkage. In the middle stage, the particle shrinks following the
      shrinking core model without change in the local conversion ratio. In the final
      stage, the local conversion ratio increases without particle shrinkage. The
      validity of the modified effective value was confirmed by comparison with
      experimental results.

PMID- 20144864
TI  - Effect of key factors on hydrogen production from cellulose in a co-culture of
      Clostridium thermocellum and Clostridium thermopalmarium.
AB  - A cellulolytic, hydrogen-producing bacterium (Clostridiumthermocellum DSM 1237)
      and a non-cellulolytic, hydrogen-producing bacterium (Clostridiumthermopalmarium
      DSM 5974) were co-cultured at 55 degrees C, using cellulose as the sole
      substrate. At a low load of cellulose (filter paper, 4.5g/L), yeast extract had a
      significant effect on cellulose degradation and hydrogen production. The extent
      of cellulose utilization and hydrogen production displayed a linear relationship
      with the logarithm of the yeast extract concentration, and the optimal weight
      ratio of yeast extract to cellulose was 1:1. At a high load of filter paper
      (9g/L), an alkali chemical was required to maintain efficient cellulose
      degradation. As the KHCO3 concentration increased from 0 to 60mM, the utilized
      cellulose increased from 1.23g/L (13.5%) to 8.59g/L (94.3%), and maximum hydrogen
      production (1387ml/L of culture) occurred at 40mM KHCO(3). Increasing the
      inoculation ratio of C. thermopalmarium to C. thermocellum from 0.05:1 to 0.17:1
      had little influence on hydrogen production, probably because of the limited
      availability of soluble sugar in the medium during the early stages of the co
      culture.

PMID- 20144865
TI  - Synthesis and evaluation of opioid receptor-binding affinity of elaeocarpenine
      and its analogs.
AB  - Both enantiomers of elaeocarpenine (1) and its analogs, 21, 22, 25, and 27, were
      synthesized from bicyclic aldehydes 8-10 via a flexible route previously
      established for total synthesis of grandisines, and their binding affinities for
      mu-, kappa- and delta-opioid receptor subtypes were evaluated. We found that (9R)
      1 exhibited higher affinity than (9S)-1 for all the subtypes, but the enantiomers
      showed little subtype selectivity. Analogs 21 having a pyrrolizidine skeleton and
      27 having a stemona-type skeleton in place of the indolizidine unit of (9S)-1
      showed mu-selective and mu-, kappa-selective binding, respectively.

PMID- 20144866
TI  - Novel pyrazolo-tetrahydropyridines as potent orexin receptor antagonists.
AB  - A novel series of dual orexin receptor antagonists was prepared by heteroaromatic
      five-membered ring system replacement of the dimethoxyphenyl moiety contained in
      the tetrahydroisoquinoline core skeleton of almorexant. Thus, replacement of the
      dimethoxyphenyl by a substituted pyrazole and additional optimization of the
      substitution pattern of the phenethyl motif allowed the identification of potent
      antagonists with low nanomolar affinity for hOX(1)R and hOX(2)R. The synthesis
      and structure-activity relationship of these novel antagonists will be discussed
      in this communication. These investigations furnished several suitable candidates
      for further evaluation in in vivo studies in rats.

PMID- 20144867
TI  - Synthesis of physostigmine analogues and evaluation of their anticholinesterase
      activities.
AB  - A series of physostigmine analogues were prepared and evaluated for
      cholinesterase inhibition activities, including acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE). Most of them showed potent inhibition activities
      against AChE, in which compound 17 especially exhibited significantly higher
      selectivity over BChE than phenserine, a compound currently on clinical trial.
      Discussion about the relationships between structure and activity of these
      derivatives was also presented.

PMID- 20144868
TI  - Semi-automated high-throughput fluorescent intercalator displacement-based
      discovery of cytotoxic DNA binding agents from a large compound library.
AB  - High-throughput fluorescent intercalator displacement (HT-FID) was adapted to the
      semi-automated screening of a commercial compound library containing 60,000
      molecules resulting in the discovery of cytotoxic DNA-targeted agents. Although
      commercial libraries are routinely screened in drug discovery efforts, the DNA
      binding potential of the compounds they contain has largely been overlooked. HT
      FID led to the rapid identification of a number of compounds for which DNA
      binding properties were validated through demonstration of concentration
      dependent DNA binding and increased thermal melting of A/T- or G/C-rich DNA
      sequences. Selected compounds were assayed further for cell proliferation
      inhibition in glioblastoma cells. Seven distinct compounds emerged from this
      screening procedure that represent structures unknown previously to be capable of
      targeting DNA leading to cell death. These agents may represent structures worthy
      of further modification to optimally explore their potential as cytotoxic anti
      cancer agents. In addition, the general screening strategy described may find
      broader impact toward the rapid discovery of DNA targeted agents with biological
      activity.

PMID- 20144869
TI  - Selective inducible microsomal prostaglandin E(2) synthase-1 (mPGES-1) inhibitors
      derived from an oxicam template.
AB  - Here we describe the SAR of a series of potent and selective mPGES-1 inhibitors
      based on an oxicam template. Compound 13j demonstrated low nanomolar mPGES-1
      inhibition in an enzyme assay. In addition, it displayed PGE(2) inhibition in a
      cell-based assay (0.42microM) and had over 238-fold selectivity for mPGES-1 over
      COX-2 and over 200-fold selectivity for mPGES-1 over 6-keto PGF(1alpha).

PMID- 20144870
TI  - Effect of linker substitution on the binding of butorphan univalent and bivalent
      ligands to opioid receptors.
AB  - A series of bivalent hydroxy ether butorphan ligands were prepared and their
      binding affinities at the opioid receptors determined. Addition of a hydroxy
      group to a hydrocarbon chain can potentiate binding affinity up to 27- and 86
      fold at the mu and kappa opioid receptors, respectively. Two bivalent ligands
      with sub-nanomolar binding affinity at the mu and kappa opioid receptors were
      discovered.

PMID- 20144871
TI  - Antiproliferative activity of novel benzo[b][1,6]naphthyridines in human solid
      tumor cell lines.
AB  - A series of 2-substituted 1,2-dihydro-3-phenyl-1
      (trichloromethyl)benzo[b][1,6]naphthyridines were synthesized and their in vitro
      antiproliferative activities were examined against human solid tumor cell lines
      and relevant strains of bacteria and Candida. The compounds induced considerably
      growth inhibition in all cancer cell lines, whilst showed inactive against
      microbial strains. Furthermore, we found analog 2-ethoxy-1H-pyrano[4,3
      b]quinoline as selective inhibitor of microbial strains.

PMID- 20144872
TI  - The decline in ascorbic acid content is associated with cadmium toxicity of rice
      seedlings.
AB  - Cadmium (Cd) toxicity of rice (Oryza sativa L. cv. Taichung Native 1) seedlings
      was evaluated by the decrease in chlorophyll content and the increase in
      malondialdehyde (MDA) in the second leaves of rice seedlings. CdCl2 (5 microM)
      treatment was accompanied by a decrease in the contents of ascorbic acid (AsA)
      and AsA + dehydroascorbate (DHA) and in the ratios of AsA/DHA in leaves. However,
      CdCl2 treatment resulted in an increase in DHA content in leaves. Moreover, the
      decrease in AsA content was prior to the occurrence of chlorosis and associated
      with the increase in MDA content in the leaves of seedlings treated with Cd.
      Pretreatment with 0.5 mM AsA or L-galactono-1,4-lactone (GalL), the biosynthetic
      precursor of AsA, for 6 h resulted in an increase in the contents of AsA and
      reduced glutathione (GSH), the ratios of AsA/DHA and GSH/oxidized glutathione,
      and the activities of ascorbate peroxidase (APX) and glutathione reductase (GR)
      in the leaves of rice seedlings. Quantitative RT-PCR was applied to quantify the
      mRNA levels for OsAPX and OsGR genes from rice leaves to examine the effect of
      AsA or GalL pretreatment on the expression of OsAPX and OsGR genes in rice
      leaves. The expression of OsAPX2, OsAPX3, OsAPX4, OsAPX5, OsAPX6, OsAPX7, and
      OsGR1 was increased by AsA or GalL pretreatment. Rice seedlings pretreated with
      AsA or GalL were observed to reduce the subsequent Cd-induced toxicity. Our
      results suggest that AsA content may play a role in regulating Cd toxicity of
      rice seedlings.

PMID- 20144873
TI  - Supramolecular structure of the OXPHOS system in highly thermogenic tissue of
      Arum maculatum.
AB  - The protein complexes of the mitochondrial respiratory chain associate in defined
      ways forming supramolecular structures called respiratory supercomplexes or
      respirasomes. In plants, additional oxidoreductases participate in respiratory
      electron transport, e.g. the so-called "alternative NAD(P)H dehydrogenases" or an
      extra terminal oxidase called "alternative oxidase" (AOX). These additional
      enzymes were previously reported not to form part of respiratory supercomplexes.
      However, formation of respiratory supercomplexes might indirectly affect
      "alternative respiration" because electrons can be channeled within the
      supercomplexes which reduces access of the alternative enzymes towards their
      electron donating substrates. Here we report an investigation on the
      supramolecular organization of the respiratory chain in thermogenic Arum
      maculatum appendix mitochondria, which are known to have a highly active AOX for
      heat production. Investigations based on mild membrane solubilization by
      digitonin and protein separation by blue native PAGE revealed a very special
      organization of the respiratory chain in A. maculatum, which strikingly differs
      to the one described for the model plant Arabidopsis thaliana: (i) complex I is
      not present in monomeric form but exclusively forms part of a I + III(2)
      supercomplex, (ii) the III(2) + IV and I + III(2) + IV supercomplexes are
      detectable but of low abundance, (iii) complex II has fewer subunits than in A.
      thaliana, and (iv) complex IV is mainly present as a monomer in a larger form
      termed "complex IVa". Since thermogenic tissue of A. maculatum at the same time
      has high AOX and I + III(2) supercomplex abundance and activity, negative
      regulation of the alternative oxidase by supercomplex formation seems not to
      occur. Functional implications are discussed.

PMID- 20144874
TI  - Restoring the spiral flow of nature in transposed great arteries.
AB  - OBJECTIVES: The great arteries are in a non-spiral relationship in their
      transposition, even after arterial switch operation (ASO) with the Lecompte
      manoeuvre. We aim to restore the natural spiral great arteries and compare such
      ASO with conventional ASO with the Lecompte manoeuvre to clarify the functional
      implications of the spiral great arteries. METHODS: The early survivors of ASO
      (n=130) were included in this retrospective study. In spiral ASO (n=48), the main
      pulmonary artery ran alongside the aorta and gave rise to its branches
      posteriorly. Patients who underwent non-spiral ASO with the manoeuvre (n=82) were
      compared. The survival, re-operation-free ratio and the anatomic details for re
      intervention after ASO were reviewed. RESULTS: Average follow-up was 5.6 + or -
      3.4 years (range: 2 months to 11 years). The estimated 10-year survival was
      similar (92.6% spiral vs 92.1% non-spiral, respectively). Significant pulmonary
      stenosis (PS) (>40mmHg) was noted in five (10.4%) in the spiral group and seven
      patients (9.7%) in the non-spiral (p=NS). The re-operation-free survival at 10
      years was not significantly different (87.4% vs 90.1%). The reasons for re
      operation were subvalvular PS (n=3) and residual defect (n=2) in the spiral
      group, while supravalvular PS (n=3), neo-aortic regurgitation (n=1) and aortic
      neo-coarctation (n=2) in the non-spiral group. Supravalvular PS and aortic neo
      coarctation that occurred in the non-spiral group were not seen after spiral ASO.
      CONCLUSIONS: Intermediate-term results of spiral ASO were satisfactory.
      Transposition is not a mere reversal of the great arteries; therefore,
      recognition of non-spiral relationship should be appreciated. Spiral
      reconstruction would be beneficial to reduce supravalvular PS and neo-aortic
      kinking. Further recognition of spiral function and refined modification might
      justify the application of spiral ASO in the future.

PMID- 20144875
TI  - Involvement of reactive oxygen species and calcium in photo-induced membrane
      damage in HeLa cells by a bis-methanophosphonate fullerene.
AB  - Photo-excited bioactivities of fullerene derivatives are attracting much
      attention. In this report, a bis-methanophosphonate fullerene (BMPF) and the
      other two fullerene derivatives, a bis-malonic acid fullerene (BMAF) and a
      fullerol were incubated with HeLa cells and irradiated with a green light emitted
      from a mercury lamp on a fluorescent microscopy. By using DNA fluorescent probe
      propidium iodide staining method, damage towards cell membrane could be detected
      when cells were treated by irradiation altogether with BMPF or BMAF at a low
      concentration (4 microM), and the damage was dose-dependent. The activity of BMPF
      was much higher than that of BMAF, while fullerol had no effects under the same
      condition. It was also revealed that different kinds of reactive oxygen species
      (ROS) correlated to BMPF and BMAF. Additionally, presence of extracellular
      calcium could promote the activities of both derivatives, while removal of
      extracellular calcium could not abort their membrane-damaged activities. These
      results indicated that ROS and calcium were involved in the photosensitization of
      fullerene derivatives, and BMPF was a superior photosensitizer which would find
      potential application in biomedical field.

PMID- 20144876
TI  - Association of TGFbeta1 polymorphisms involved in radiation toxicity with
      TGFbeta1 secretion in vitro.
AB  - TGFbeta1 plasma levels and TGFbeta1 genetic polymorphisms have been linked to
      radiation-induced lung injury. As the correlation between plasma levels and
      genotype is not always straightforward, this study investigated the association
      between TGFbeta1 genotype, considering several polymorphisms, and in vitro
      TGFbeta1 secretion of human lymphocytes. Four polymorphisms in TGFbeta1 (c.-800,
      c.-509, c.29, c.74) affecting TGFbeta1 secretion and a deletion (c.69_77del9) in
      TGFbetaR1 influencing TGFbeta1 signaling were genotyped in 250 healthy
      individuals. TGFbeta1 levels were determined for 10 individuals with wild type
      alleles for all considered polymorphisms and for 21 individuals harboring variant
      alleles of a single polymorphism and no variant alleles at any other considered
      polymorphic location. After cell proliferation and cell viability quality control
      criteria, TGFbeta1 levels were obtained for 17 individuals. Mean TGFbeta1 levels
      were 1046.2pg, 566.7pg, 740.6pg, 1001.8pg, 701.2pg and 2844pg per 10(6)cells for,
      respectively, c.-800 heterozygous, c.-509/c.29 heterozygous, c.-509/c.29
      homozygous variant, c.69_77del9 heterozygous and c.69_77del9 homozygous variant
      cells. Only for c.-800 heterozygous cells this difference was borderline
      statistically significant compared to wild type cells (p=0.071). In conclusion,
      the effect of genetic polymorphisms in TGFbeta1/TGFbetaR1 on secreted TGFbeta1
      levels in vitro could not be clarified. The inter-individual variation in
      TGFbeta1 levels for individuals with the same genotype was too large to obtain
      statistically significant differences among genotypes.

PMID- 20144877
TI  - Runx family genes, niche, and stem cell quiescence.
AB  - In multicellular organisms, terminally differentiated cells of most tissues are
      short-lived and therefore require constant replenishment from rapidly dividing
      stem cells for homeostasis and tissue repair. For the stem cells to last
      throughout the lifetime of the organism, however, a small subset of stem cells,
      which are maintained in a hibernation-like state known as stem cell quiescence,
      is required. Such dormant stem cells reside in the niche and are activated into
      proliferation only when necessary. A multitude of factors are required for the
      maintenance of stem cell quiescence and niche. In particular, the Runx family
      genes have been implicated in stem cell quiescence in various organisms and
      tissues. In this review, we discuss the maintenance of stem cell quiescence in
      various tissues, mainly in the context of the Runx family genes, and with special
      focus on the hematopoietic system.

PMID- 20144878
TI  - Molecular-biological analysis of the effect of methamphetamine on the heart in
      restrained mice.
AB  - In order to investigate the interaction in the heart between the administration
      of methamphetamine (MAP) and restraint of the body following it, we administrated
      MAP intraperitoneally to mice and restrained them, and then determined the level
      of mRNA expression of 22 genes in the heart using quantitative RT-PCR method. The
      mRNA expressions of Nfkbiz, Nr4a1 and Dusp1 changed significantly after the
      administration of MAP, suggesting the induction of an inflammatory condition such
      as damage to the myocardium. Moreover, the serum concentrations of inflammatory
      cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1 beta and IL-6
      were significantly increased by the administration of MAP. On the other hand, the
      mRNA expressions of Rgs2 and Rasd1 were changed by both the administration of MAP
      and body restraint without interaction, which indicated that these insults
      affected the circulatory system additively or synergistically. From these
      results, it is likely that the administration of MAP, followed by body restraint,
      might cause acute myocardial damage due to the direct myocardial toxic effect of
      MAP, myocardial hypoxia and/or severe hypertension, which is one of the
      mechanisms for sudden death in MAP abusers who were restrained due to their
      excited state.

PMID- 20144879
TI  - Evaluation of the anticonvulsant effect of Centella asiatica (gotu kola) in
      pentylenetetrazol-induced seizures with respect to cholinergic neurotransmission.
AB  - The study described here was carried out to investigate the anticonvulsant effect
      of different extracts of Centella asiatica with respect to cholinergic activity
      on pentylenetetrazol (PTZ)-induced seizures. Rats were randomly divided into
      eight groups of six rats each: nonepileptic rats treated with saline; PTZ (60
      mg/kg, IP)-induced seizure rats treated with saline; PTZ-induced seizure rats
      pretreated with n-hexane, chloroform, ethyl acetate, n-butanol, and water
      extracts of C. asiatica; and PTZ-induced seizure rats pretreated with diazepam
      (2mg/kg body wt). The seized rats pretreated with different extracts were
      administered a dose of 200mg/kg body wt orally for 1 week before induction of
      epilepsy. Increased acetylcholine content and decreased acetylcholinesterase
      activity were recorded in different brain regions during PTZ-induced seizures.
      Pretreatment with C. asiatica extracts caused recovery of the levels of
      acetylcholine and acetylcholinesterase. These findings suggest that C. asiatica
      causes perceptible changes in the cholinergic system as one of the facets of its
      anticonvulsant activity.

PMID- 20144880
TI  - Commentary on "Stimulation-based anticipation and control of state transitions in
      the epileptic brain" by Kalitzin, Velis, and Lopes da Silva.

PMID- 20144881
TI  - Salivary alpha amylase activity in migraine patients.
AB  - OBJECTIVE: Salivary alpha amylase levels were measured to investigate sympathetic
      nervous system activity in migraine patients during attack, post-attack and
      interval periods of headache since salivary alpha amylase levels have been
      suggested as a potential indirect marker of sympatho-adrenal medullary activity
      in recent studies. METHODS: 50 patients with migraine headache (13 patients in
      attack, 26 patients in post-attack and 11 patients in interval period) and 60
      healthy volunteers were taken into the study. In all participants, the presence
      of anxiety was measured by using Hamilton Anxiety Rating scale. The visual analog
      scale scores for pain level estimation were obtained in the attack group.
      RESULTS: The salivary alpha amylase levels were significantly lower in attack
      period (p<0.01) and higher in post-attack period (p<0.01) when compared with the
      control group. There was not any significant difference in salivary alpha amylase
      levels between interval period and control group (p>0.05). There was a weak
      negative correlation between the salivary alpha amylase levels and the visual
      analog scale scores. CONCLUSIONS: This is the first study showing the dynamic
      nature of sympathetic nervous system activity by evaluating the salivary alpha
      amylase levels-a noninvasive, reliable and an easy method-in different periods of
      migraine headache.

PMID- 20144883
TI  - Restoring the charge and surface activity of bovine lung extract surfactants with
      cationic and anionic polysaccharides.
AB  - Chitosan, a cationic polysaccharide, has been found to improve the surface
      activity of lung surfactant extracts in the presence of various inhibitors. It
      has been proposed that chitosan binds to anionic lipids (e.g. phosphatidyl
      glycerols) in lung surfactants, producing stable lipid films at the air-water
      interface. This binding also reverses the net charge of the surfactant
      aggregates, from negative to positive. Unfortunately, positively charged
      aggregates may adsorb or interact with the negatively charged epithelial tissue,
      leading to poor surfactant performance. To address this issue an anionic
      polysaccharide, dextran sulfate (dexS), was used as a secondary coating to
      reverse the charge of chitosan-lung surfactant extracts without affecting the
      surface activity of the preparation. The dynamic surface tension and zeta
      potential of bovine lipid extract surfactant (BLES) containing chitosan chloride
      (chiCl) and dexS were evaluated as a function of dexS concentration. These
      studies were conducted in the absence and presence of sodium bicarbonate buffer,
      and in the absence and presence of bovine serum used as model inhibitor. It was
      determined that using an appropriate concentration of dexS, especially at
      physiological pH, it is possible to restore the negative charge of the surfactant
      aggregates, and retain their surface activity, even in the presence of bovine
      serum. High concentrations of dexS affect the binding of chiCl to BLES, and the
      surface activity of the preparation.

PMID- 20144882
TI  - The dopamine-D2-receptor agonist ropinirole dose-dependently blocks the Ca2+
      triggered permeability transition of mitochondria.
AB  - Ropinirole, an agonist of the post-synaptic dopamine D2-receptor, exerts
      neuroprotective activity. The mechanism is still under discussion. Assuming that
      this neuroprotection might be associated with inhibition of the apoptotic cascade
      underlying cell death, we examined a possible effect of ropinirole on the
      permeability transition pore (mtPTP) in the mitochondrial inner membrane. Using
      isolated rat liver mitochondria, the effect of ropinirole was studied on Ca2+
      triggered large amplitude swelling, membrane depolarization and cytochrome c
      release. In addition, the effect of ropinirole on oxidation of added, membrane
      impermeable NADH was investigated. The results revealed doubtlessly, that
      ropinirole can inhibit permeability transition. In patch-clamp experiments on
      mitoplasts, we show directly that ropinirole interacts with the mtPTP. Thus,
      ropinirole reversibly inhibits the opening of mtPTP with an IC50 of 3.4 microM
      and a Hill coefficient of 1.3. In both systems (i.e. energized mitochondria and
      mitoplasts) the inhibitory effect on permeability transition was attenuated by
      increasing concentrations of inorganic phosphate. In addition, we showed with
      antimycin A-treated mitochondria that ropinirole failed to suppress respiratory
      chain-linked reactive oxygen species release. In conclusion, our data suggest
      that the neuroprotective activity of ropinirole is due to the blockade of the
      Ca2+-triggered permeability transition.

PMID- 20144884
TI  - Regulatory volume increase in epithelial cells isolated from the mouse fourth
      ventricle choroid plexus involves Na(+)-H(+) exchange but not Na(+)-K(+)-2Cl(-)
      cotransport.
AB  - The aim of this study was to determine the ability of choroid plexus epithelial
      cells to volume regulate when exposed to hypertonic solutions, and furthermore to
      identify the ion transporters involved in any volume regulation. Experiments were
      performed on cells freshly isolated, using the enzyme dispase, from the mouse
      fourth ventricle choroid plexus. Cell volume was measured using a video-imaging
      method. Cells used in this study were all of a similar morphology and had a mean
      volume of 0.71pl. Cells shrank when superfused with hypertonic solutions to a
      minimum relative cell volume of 0.84+/-0.01 (n=8) in 3min. They then exhibited a
      regulatory volume increase (RVI) to reach a relative volume of 0.92+/-0.02 over
      the following 12min. The RVI was HCO(3)(-)-dependent, that is it was not observed
      in hepes-buffered solutions. A post-regulatory volume decrease RVI (post-RVD RVI)
      was also observed in cells following exposure to hypotonic solutions. The RVI and
      post-RVD RVI were inhibited by 10microM 5-(N-ethyl-N-isopropyl) amiloride or
      10microM 5-(N-methyl-N-isobutyl) amiloride, both selective inhibitors of Na(+)
      H(+) exchange (NHE). They were also inhibited by the anion transport inhibitor
      100microM 2,2'-(1,2-ethenediyl) bis (5-isothiocyanatobenzenesulfonic acid). The
      Na(+)-K(+)-2Cl(-) cotransporter inhibitor, 10microM bumetanide, was without
      effect on either the RVI or the post-RVD RVI. The data indicate that NHE,
      probably in combination with Cl(-)-HCO(3)(-) exchangers, contributes to RVI in
      choroid plexus epithelial cells.

PMID- 20144886
TI  - Differential regulation of dendritic plasticity by neurotrophins following
      deafferentation of the adult spinal cord is independent of p75(NTR).
AB  - Spontaneous and/or treatment-evoked re-modeling of the CNS following spinal cord
      injury is a prerequisite for functional recovery. While there has been
      considerable interest in the role of endogenous neurotrophins in spontaneous
      plasticity of several populations of spinal axons, the same cannot be said for
      morphological changes to dendrites. Here, we examined the responses of dendrites
      in the mouse lateral spinal nucleus (LSN, a site of sensory integration in the
      dorsolateral white matter) to exogenous and endogenous neurotrophins. We
      performed a septuple dorsal rhizotomy, which permanently eliminates sensory input
      to the spinal cord, and stimulates sprouting of spinal axons. While dendrites
      showed no change in density following injury alone, they sprouted vigorously (a
      two-fold increase in density) upon addition of exogenous brain-derived
      neurotrophic factor (BDNF). On the other hand, endogenous nerve growth factor
      (NGF) severely restricted dendritic sprouting, as TrkA-Fc treatment also roughly
      doubled the density of dendritic processes in the LSN. Spontaneous, BDNF- and
      TrkA-Fc mediated sprouting was unaffected by the absence of p75(NTR).
      Importantly, TrkA-Fc treatment markedly reduced expression of the truncated BDNF
      receptor TrkBT1 in both p75(+/+) and p75(-/-) mice, which was robustly
      upregulated by deafferentation in both genotypes. We propose that the
      upregulation of TrkBT1 by NGF results in a reduced availability of endogenous
      BDNF to dendrites. Accordingly, sprouting of serotonergic axons, a BDNF-dependent
      consequence of dorsal root injury, was significantly enhanced in TrkA-Fc-treated
      animals. These results suggest that NGF and BDNF signaling differentially
      regulates dendritic plasticity in the deafferented spinal cord.

PMID- 20144885
TI  - Distribution of hypothalamic neurons with orexin (hypocretin) or melanin
      concentrating hormone (MCH) immunoreactivity and multisynaptic connections with
      diaphragm motoneurons.
AB  - Prior work showed that neurons in the lateral, dorsal, and perifornical regions
      of the tuberal and mammillary levels of the hypothalamus participate in the
      control of breathing. The same areas also contain large numbers of neurons that
      produce either orexins (hypocretins) or melanin concentrating hormone (MCH).
      These peptides have been implicated in regulating energy balance and
      physiological changes that occur in transitions between sleep and wakefulness,
      amongst other functions. The goal of this study was to determine if hypothalamic
      neurons involved in respiratory control, which were identified in cats by the
      retrograde transneuronal transport of rabies virus from the diaphragm, were
      immunopositive for either orexin-A or MCH. In animals with limited rabies
      infection of the hypothalamus (<10 infected cells/section), where the neurons
      with the most direct influences on diaphragm motoneurons were presumably labeled,
      a large fraction (28-75%) of the infected hypothalamic neurons contained orexin
      A. In the same cases, 6-33% of rabies-infected hypothalamic cells contained MCH.
      However, in animals with more extensive infection, where rabies had presumably
      passed transneuronally through more synapses, the fraction of infected cells that
      contained orexin-A was lower. The findings from these experiments thus support
      the notion that hypothalamic influences on breathing are substantially mediated
      through orexins or MCH.

PMID- 20144887
TI  - Long-term survival and development of fetal ventral spinal grafts into the
      motoneuron-depleted rat spinal cord: role of donor age.
AB  - Fetal spinal cord (SC) tissue grafts can survive and develop into the lesioned
      SC, but no conclusive data are available concerning the long-term fate of
      transplanted material and the relation between the graft fate and the donor
      embryo age. Here, pre-labelled suspensions of ventral SC from E12 or E17 rat
      fetuses were grafted to the lumbar SC of adult rats with motoneuron depletion
      induced by perinatal injection of volkensin. E12 and E17 are presumably the
      stages when motoneuron development starts and terminates, respectively. Four or
      10months post-grafting, SCs were analyzed to check the graft survival rate and to
      follow the differentiation and spatial distributions of grafted cells. Neurotoxic
      lesion produced a 61% motoneuronal loss in the lumbar SC. In transplanted
      animals, all E12 fetal grafts survived until the observed time-points and
      developed various mature cell phenotypes. Many motoneuron-like labelled cells
      were found within the graft area or adjacent to it. Conversely, none of the E17
      fetal grafts survived, since no graft-derived elements with neuronal morphology
      were found either in the site of graft placement or adjacent to it. The present
      findings indicate that spinal neuroblasts can survive for a long time and develop
      within the motoneuron-depleted SC, and that the donor embryo age is crucial for
      successful engraftment.

PMID- 20144888
TI  - Prostaglandin E2 reduces amyloid beta-induced phagocytosis in cultured rat
      microglia.
AB  - Treatment with amyloid beta(1-42) (Abeta(1-42)) at 1microM for 60min increased
      phagocytosis of latex beads by cultured rat microglia. This increase was reduced
      dose-dependently by prostaglandin E(2) (PGE(2)), but PGD(2), PGF(2alpha),
      iloprost, or U-46619 had no effects. PGE(2) also reduced the phagocytosis of
      fluorescent-labeled Abeta(1-42). Abeta(1-42)-induced phagocytosis was reduced by
      butaprost but not by 17-phenyl trinor PGE(2), sulprostone, or PGE(1) alcohol. The
      reduction effect of PGE(2) on phagocytosis was reversed by AH6809, an E
      prostanoid receptor 2 (EP2) antagonist, which inhibited cyclic adenosine
      monophosphate (AMP) accumulation induced by PGE(2). Butaprost, but not 17-phenyl
      trinor PGE(2), sulprostone, or PGE(1) alcohol increased intracellular cyclic AMP
      accumulation. In western blotting analysis, EP2-like immunoreactivity was
      detected in the crude membrane fraction of microglia. On the other hand, Abeta(1
      42)-induced phagocytosis was not affected by SC-560, a cyclooxygenase-1 (COX-1)
      inhibitor, NS-398, a COX-2 inhibitor, or ibuprofen, a non-specific COX inhibitor.
      Abeta(1-42) or PGE(2) had little effect on the expression levels of COX-1 or COX
      2. These results indicate that Abeta(1-42)-induced microglial phagocytosis is
      reduced by PGE(2) through EP2.

PMID- 20144889
TI  - Protection by pyridostigmine bromide of marmoset hemi-diaphragm
      acetylcholinesterase activity after soman exposure.
AB  - Pyridostigmine bromide (PB) was approved by the U.S. Food and Drug Administration
      (FDA) in 2003 as a pretreatment in humans against the lethal effects of the
      irreversible nerve agent soman (GD). Organophosphate (OP) chemical warfare agents
      such as GD exert their toxic effects by inhibiting acetylcholinesterase (AChE)
      from terminating the action of acetylcholine at postsynaptic sites in cholinergic
      nerve terminals (including crucial peripheral muscle such as diaphragm). As part
      of the post-marketing approval of PB, the FDA required (under 21CFR314, the "two
      animal rule") the study of a non-human primate model (the common marmoset
      Callithrix jacchus jacchus) to demonstrate increased survival against lethal GD
      poisoning, and protection of physiological hemi-diaphragm function after PB
      pretreatment and subsequent GD exposure. Marmosets (male and female) were placed
      in the following experimental groups: (i) control (saline pretreatment only),
      (ii) low dose PB (12.5 microg/kg), or (iii) high dose (39.5 microg/kg) PB. Thirty
      minutes after the PB dose, animals were challenged with either saline (control)
      or soman (GD, 45 microg/kg), followed 1 min later by atropine (2mg/kg) and 2-PAM
      (25mg/kg). After a further 16 min, animals were euthanized and the complete
      diaphragm removed; the right hemi-diaphragm was frozen immediately at -80 degrees
      C, and the left hemi-diaphragm was placed in a tissue bath for 4h (to allow for
      decarbamylation to occur), then frozen. AChE activities were determined using the
      automated WRAIR cholinesterase assay. Blood samples were collected for AChE
      activities prior to PB, before GD challenge, and after sacrifice. RBC-AChE was
      inhibited by approximately 18% and 50% at the low and high doses of PB,
      respectively, compared to control (baseline) activity. In the absence of PB
      pretreatment, the inhibition of RBC-AChE by GD was 98%. The recovery of hemi
      diaphragm AChE activity after the 4h wash period (decarbamylation) was
      approximately 8% and 17%, at the low and high PB doses, respectively, compared
      with the baseline (control) AChE activity prior to PB pretreatment or soman
      exposure. The results suggest that PB pretreatment protects a critical fraction
      of AChE activity in the marmoset diaphragm, which is sufficient to allow the
      animal to breathe despite exposure to a dose of soman that is lethal in
      unprotected animals.

PMID- 20144890
TI  - Theophylline treatment improves mitochondrial function after upper cervical
      spinal cord hemisection.
AB  - The importance of mitochondria in spinal cord injury has mainly been attributed
      to their participation in apoptosis at the site of injury. But another aspect of
      mitochondrial function is the generation of more than 90% of cellular energy in
      the form of ATP, mediated by the oxidative phosphorylation (OxPhos) process.
      Cytochrome c oxidase (CcO) is a central OxPhos component and changes in its
      activity reflect changes in energy demand. A recent study suggests that
      respiratory muscle function in chronic obstructive pulmonary disease (COPD)
      patients is compromised via alterations in mitochondrial function. In an animal
      model of cervical spinal cord hemisection (C2HS) respiratory dysfunction, we have
      shown that theophylline improves respiratory function. In the present study, we
      tested the hypothesis that theophylline improves respiratory function at the
      cellular level via improved mitochondrial function in the C2HS model. We
      demonstrate that CcO activity was significantly (33%) increased in the spinal
      cord adjacent to the site of injury (C3-C5), and that administration of
      theophylline (20mg/kg 3x daily orally) after C2HS leads to an even more
      pronounced increase in CcO activity of 62% compared to sham-operated animals.
      These results are paralleled by a significant increase in cellular ATP levels
      (51% in the hemidiaphragm ipsilateral to the hemisection). We conclude that C2HS
      increases energy demand and activates mitochondrial respiration, and that
      theophylline treatment improves energy levels through activation of the
      mitochondrial OxPhos process to provide energy for tissue repair and functional
      recovery after paralysis in the C2HS model.

PMID- 20144891
TI  - The conditioning lesion effect on sympathetic neurite outgrowth is dependent on
      gp130 cytokines.
AB  - Sympathetic neurons, like sensory neurons, increase neurite outgrowth after a
      conditioning lesion. Studies in leukemia inhibitory factor (LIF) knockout animals
      showed that the conditioning lesion effect in sensory neurons is dependent in
      part on this cytokine; however, similar studies on sympathetic neurons revealed
      no such effect. Comparable studies with sensory neurons taken from mice lacking
      the related cytokine interleukin-6 (IL-6) have yielded conflicting results. LIF
      and IL-6 belong to a family of cytokines known as the gp130 family because they
      act on receptors containing the subunit gp130. In sympathetic ganglia, axotomy
      leads to increases in mRNA for four of these cytokines (LIF, IL-6, IL-11, and
      oncostatin M). To test the role of this family of cytokines as a whole in the
      conditioning lesion response in sympathetic neurons, mice in which gp130 was
      selectively eliminated in noradrenergic neurons were studied. The postganglionic
      axons of the SCG were transected, and 7days later the ganglia were removed and
      neurite outgrowth was measured in explant and dissociated cell cultures. In both
      systems, neurons from wild type animals showed enhanced growth after a
      conditioning lesion. In contrast, no enhancement occurred in neurons from mutant
      animals. This lack of stimulation of outgrowth occurred despite an increase in
      expression of activating transcription factor 3 (ATF3) in the mutant mice. These
      studies demonstrate that stimulation of enhanced growth of sympathetic neurons
      after a conditioning lesion is dependent on gp130 cytokine signaling and is
      blocked in the absence of signaling by these cytokines in spite of an increase in
      ATF3.

PMID- 20144892
TI  - Effects of TRPV1 activation on synaptic excitation in the dentate gyrus of a
      mouse model of temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) is a condition characterized by an imbalance between
      excitation and inhibition in the temporal lobe. Hallmarks of this change are axon
      sprouting and accompanying synaptic reorganization in the temporal lobe.
      Synthetic and endogenous cannabinoids have variable therapeutic potential in
      treating intractable temporal lobe epilepsy, in part because cannabinoid ligands
      can bind multiple receptor types. This study utilized in vitro
      electrophysiological methods to examine the effect of transient receptor
      potential vanilloid type 1 (TRPV1) activation in dentate gyrus granule cells in a
      murine model of TLE. Capsaicin, a selective TRPV1 agonist had no measurable
      effect on overall synaptic input to granule cells in control animals, but
      significantly enhanced spontaneous and miniature EPSC frequency in mice with TLE.
      Exogenous application of anandamide, an endogenous cannabinoid that acts at both
      TRPV1 and cannabinoid type 1 receptors (CB1R), also enhanced glutamate release in
      the presence of a CB1R antagonist. Anandamide reduced the EPSC frequency when
      TRPV1 were blocked with capsazepine. Western blot analysis of TRPV1 receptor
      indicated protein expression was significantly greater in the dentate gyrus of
      mice with TLE compared with control mice. This study indicates that a prominent
      cannabinoid agonist can increase excitatory circuit activity in the synaptically
      reorganized dentate gyrus of mice with TLE by activating TRPV1 receptors, and
      suggests caution in designing anticonvulsant therapy based on modulating the
      endocannabinoid system.

PMID- 20144893
TI  - The limits of agency in walking humans.
AB  - An important principle of human ethics is that individuals are not responsible
      for actions performed when unconscious. Recent research found that the generation
      of an action and the building of a conscious experience of that action (agency)
      are distinct processes and crucial mechanisms for self-consciousness. Yet,
      previous agency studies have focussed on actions of a finger or hand. Here, we
      investigate how agents consciously monitor actions of the entire body in space
      during locomotion. This was motivated by previous work revealing that (1) a
      fundamental aspect of self-consciousness concerns a single and coherent
      representation of the entire spatially situated body and (2) clinical instances
      of human behaviour without consciousness occur in rare neurological conditions
      such as sleepwalking or epileptic nocturnal wandering. Merging techniques from
      virtual reality, full-body tracking, and cognitive science of conscious action
      monitoring, we report experimental data about consciousness during locomotion in
      healthy participants. We find that agents consciously monitor the location of
      their entire body and its locomotion only with low precision and report that
      while precision remains low it can be systematically modulated in several
      experimental conditions. This shows that conscious action monitoring in
      locomoting agents can be studied in a fine-grained manner. We argue that the
      study of the mechanisms of agency for a person's full body may help to refine our
      scientific criteria of self-hood and discuss sleepwalking and related conditions
      as alterations in neural systems encoding motor awareness in walking humans.

PMID- 20144895
TI  - Comparative analyses of venoms from American and African Sicarius spiders that
      differ in sphingomyelinase D activity.
AB  - Spider venoms are cocktails of toxic proteins and peptides, whose composition
      varies at many levels. Understanding patterns of variation in chemistry and
      bioactivity is fundamental for understanding factors influencing variation. The
      venom toxin sphingomyelinase D (SMase D) in sicariid spider venom (Loxosceles and
      Sicarius) causes dermonecrotic lesions in mammals. Multiple forms of venom
      expressed genes with homology to SMase D are expressed in venoms of both genera.
      SMase D activity levels differ among major clades with American Sicarius vastly
      reduced relative to all Loxosceles and African Sicarius despite expression of
      SMase D homologs in venoms of American Sicarius. Here we report comparative
      analyses of protein composition and insecticidal activity of crude venoms from
      three Sicarius species, two from South Africa and one from Central America.
      Comparative 2-dimensional electrophoresis shows dense regions of proteins in the
      size range of SMase D in all three species, but there are differences in sizes
      and isoelectric points (pIs). Few proteins strictly co-migrate and there are
      clusters of proteins with similar pIs and molecular weights whose patterns of
      similarity do not necessarily reflect phylogenetic relatedness. In addition,
      PD(50) estimates on crickets indicate a small though significant decrease in
      potency of South American Sicarius venoms relative to African species.

PMID- 20144894
TI  - An animal model of recognition memory and medial temporal lobe amnesia: history
      and current issues.
AB  - The medial temporal lobe includes a system of anatomically connected structures
      that are essential for declarative memory (conscious memory for facts and
      events). A prominent form of declarative memory is recognition memory (the
      ability to identify a recently encountered item as familiar). Recognition memory
      has been frequently assessed in humans and in the experimental animal. This
      article traces the successful development of an animal model of human medial
      temporal lobe amnesia, which eventually identified the structures in the medial
      temporal lobe important for memory. Attention is given to two prominent
      behavioral paradigms (delayed nonmatching to sample and tests of spontaneous
      novelty preference).

PMID- 20144897
TI  - Positive predictive value of the UK clinical case definition for H1N1/09
      ('swine') influenza.

PMID- 20144896
TI  - Molecular characterization and expression of a crustin-like gene from Chinese
      mitten crab, Eriocheir sinensis.
AB  - Crustin is a cysteine-rich antibacterial peptide which widely distributes within
      decapod crustaceans. In the present study, the cDNA encoding crustin-like peptide
      (designated CrusEs) was cloned from Chinese mitten crab Eriocheir sinensis by
      using rapid amplification of cDNA ends (RACE) approaches and expressed sequence
      tag analysis. The full-length cDNA of CrusEs was of 796bp, containing a 5'
      untranslated region (UTR) of 214bp, a 3' UTR of 267bp with a poly(A) tail, and an
      open reading frame (ORF) of 315bp encoding a polypeptide of 104 amino acids
      including a putative signal peptide of 21 amino acids. A WAP domain and the
      consensus framework existing in class I crustins were both identified in CrusEs,
      suggesting that CrusEs is a new member of type I crustins. Quantitative real-time
      RT-PCR was employed to examine the expression of CrusEs, and its mRNA transcript
      was mainly detected in haemocytes and gill. The CrusEs mRNA transcript in
      haemocytes was down-regulated after the challenge with Gram-positive bacteria
      Micrococcus luteus, while Gram-negative bacteria Listonella anguillarum did not
      induce significant variation of CrusEs mRNA. The mature peptide of CrusEs was
      cloned into pET-21a(+) with a C-terminal hexa-histidine tag fused in-frame, and
      expressed in Escherichia coli, and the recombinant CrusEs inhibited the growth of
      Gram-positive bacteria with low MIC. The results indicate that CrusEs is a potent
      antibacterial protein against Gram-positive bacteria infection, and it may play
      an important role in innate immune response of E. sinensis.

PMID- 20144898
TI  - Fecal carriage of CTXM type extended-spectrum beta-lactamase-producing organisms
      by children and their household contacts.
AB  - OBJECTIVES: To investigate the epidemiology of fecal carriage of CTX-M type
      extended-spectrum beta-lactamases (ESBL)-producing organisms among children and
      their household contacts. METHODS: Fecal carriage with CTX-M-producing organisms
      was studied in 53 children and 172 household members. Molecular methods were used
      to characterize the isolates. RESULTS: The children were mostly healthy and
      hospitalized for relatively mild febrile illnesses. Overall, the prevalence of
      fecal carriage of CTX-M-producing bacteria was 43.5% (admission children, 37.7%;
      household children, 20.7% and household adults, 50.3%). Household colonization
      index (defined by number of household carriers/total number of members) was
      significantly higher among families with at least one individual having a history
      of prolonged (>3 months) out-of-town residence in the previous year (mean+/
      standard deviation; yes group, 0.67+/-0.36 vs. no group, 0.39+/-0.28, P=0.009)
      and was inversely correlated with the living space per person (R-square=0.139,
      P=0.006). Among 29 households with at least two carriers of CTX-M-producing
      enterobacteria, six clusters of clonally related strains were shared by 15
      individuals from seven households; with both intra- and inter-household
      transmission. CONCLUSION: CTX-M beta-lactamases may spread extensively amongst
      family members in the home.

PMID- 20144899
TI  - Activity of tigecycline against Streptococcus pneumoniae, an important causative
      pathogen of community-acquired pneumonia (CAP).

PMID- 20144900
TI  - Activity-dependent changes in the electrophysiological properties of regular
      spiking neurons in the sensorimotor cortex of the rat in vitro.
AB  - Sensorimotor performance is highly dependent on the level of physical activity.
      For instance, a period of disuse induces an impairment of motor performance,
      which is the result of combined muscular, spinal and supraspinal mechanisms.
      Concerning this latter origin, our hypothesis was that intrinsic properties and
      input/output coupling of cells within the sensorimotor cortex might participate
      to the alteration in cortical motor control. The aim of the present study was
      thus to examine the basic electrophysiological characteristics of cortical cells
      in control rats and in animals submitted to 14 days of hindlimb unloading, a
      model of sensorimotor deprivation. Intracellular recordings were obtained in
      vitro from coronal slices from cortical hindpaw representation area. We have also
      made an attempt to determine the morphological characteristics as well as the
      location of the investigated neurons by biocytin labelling. Passive properties of
      neurons were affected by hindlimb unloading: input resistance and time constant
      were decreased (-20%), the rheobase was increased (+34%), whereas the resting
      potential was unchanged. The frequency-current relationships were also modified,
      the curve being shifted towards right. The size of body area of recorded neurons
      was unchanged in unloaded rats. Taken together, these data reflect a decrease in
      excitability of cortical cells in response to a decreased cortical activation.

PMID- 20144901
TI  - The CCK(2) receptor antagonist, YF476, inhibits Mastomys ECL cell hyperplasia and
      gastric carcinoid tumor development.
AB  - YF476 is a potent and highly selective cholecystokin 2 (CCK(2)) receptor
      antagonist of the benzodiazepine class. It inhibits gastric neuroendocrine
      enterochromaffin-like (ECL) cell secretion, proliferation and spontaneous
      formation of gastric neuroendocrine tumors (carcinoids) in cotton rats. The
      Mastomys rodent species exhibits a genetic predisposition to gastric ECL
      neuroendocrine tumor formation which can be accelerated by acid suppression and
      induction of hypergastrinemia. In this respect, it mimics the human condition of
      atrophic gastritis, hypergastrinemia and gastric carcinoid development. We
      investigated whether YF476 could inhibit acid suppression-induced ECL cell
      hyperplasia and neoplasia in this model. In addition, we examined whether YF476
      could reverse established ECL cell hyperplasia and neoplasia. Targeting the
      CCK(2) receptor during Loxtidine-induced hypergastrinemia resulted in a reduction
      in ECL cell secretion (plasma and mucosal histamine, and histidine decarboxylase
      (HDC) transcripts, p<0.05) and proliferation (numbers of HDC-positive cells,
      connective tissue growth factor (CTGF) and cyclin D1 transcription). This was
      associated with a decrease in ECL cell hyperplasia and a 60% reduction in gastric
      ECL cell microcarcinoid (tumors <0.3mm in size) formation. YF476 inhibited ECL
      cell neoplasia (gastric carcinoid) in animals with hyperplasia, inhibited the
      formation of ECL cell tumors when co-administered with Loxtidine and reversed the
      growth and developement of gastric ECL cell carcinoids in long-term acid
      suppressed Mastomys. Variable importance analysis using a logistic multinomial
      regression model indicated the effects of YF476 were specific to the ECL cell and
      alterations in ECL cell function reflected inhibition of transcripts for HDC,
      Chromogranin A (CgA), CCK(2) and the autocrine growth factor, CTGF. We conclude
      that specifically targeting the CCK(2) receptor inhibits gastrin-mediated ECL
      cell secretion and ECL cell proliferation and tumor development in vivo.

PMID- 20144902
TI  - Moonlighting proteins: an intriguing mode of multitasking.
AB  - Proteins are macromolecules, which perform a large variety of functions. Most of
      them have only a single function, but an increasing number of proteins are being
      identified as multifunctional. Moonlighting proteins form a special class of
      multifunctional proteins. They perform multiple autonomous and often unrelated
      functions without partitioning these functions into different domains of the
      protein. Striking examples are enzymes, which in addition to their catalytic
      function are involved in fully unrelated processes such as autophagy, protein
      transport or DNA maintenance. In this contribution we present an overview of our
      current knowledge of moonlighting proteins and discuss the significant
      implications for biomedical and fundamental research.

PMID- 20144903
TI  - Identification of natural recombination in duck hepatitis B virus.
AB  - Due to its high similarity to human hepatitis B virus (HBV), duck HBV (DHBV) is
      often used as an important model for HBV research. While inter-genotypic
      recombination of HBV is common, it has not been reported with DHBV. In this
      study, 32 non-redundant DHBV complete genomes were analyzed using phylogenetic
      methods and classified into two clusters, corresponding to the 'Chinese' and
      'Western country' branches previously reported based on geographical
      distribution. One 'Chinese' branch strain was isolated in Australia and three
      'Western country' branch strains were isolated in China, suggesting cross
      geographical distribution of both branches. Recombination analyses of the 32 DHBV
      genomes identified two possible inter-genotypic recombination events with high
      confidence value. These recombination events occurred between the lineages
      represented, respectively, by the Chinese isolate GD3 (AY536371, 'Chinese'
      branch) and the American isolate DHBV16 (K01834, 'Western country' branch),
      giving rise to two Chinese recombinant isolates CH4 (EU429324) and CH6
      (EU429326). The identification of inter-genotypic recombination among circulating
      DHBV isolates suggests the usefulness of DHBV as a model for studying the
      mechanism of HBV recombination.

PMID- 20144904
TI  - The early noncoding region of human papillomavirus type 16 is regulated by
      cytoplasmic polyadenylation factors.
AB  - All human papillomavirus type 16 (HPV-16) early mRNAs are polyadenylated at the
      poly(A) signal within the early 3' untranslated region (3'UTR). The 3'end of the
      early E5 open reading frame and the 3'UTR of HPV-16 is very AU-rich, with five
      regions similar to cytoplasmic polyadenylation elements (CPEs). We show here that
      a fragment of the early 3'end comprising four of the five CPE-like regions when
      inserted downstream of a reporter gene confers regulation of the gene expression.
      A key protein involved in cytoplasmic polyadenylation is CPEB. We show that the
      human CPEB1 can repress the activity of the reporter construct containing the HPV
      16 early sequences. This repression can be counteracted by a human cytoplasmic
      poly(A) polymerase, hGLD-2 fused to CPEB1. The hGLD-2/CPEB1 fusion protein
      facilitates furthermore poly(A) elongation of early HPV transcripts.

PMID- 20144905
TI  - Thiol-disulfide exchanges modulate aldo-keto reductase family 1 member B10
      activity and sensitivity to inhibitors.
AB  - The reversible thiol/disulfide exchange is an important regulatory mechanism of
      protein enzymatic activity. Many protein enzymes are susceptible to S-thiolation
      induced by reactive oxygen species (ROS); and the glutathione (GSH) and free
      amino acid cysteine (Cys) are critical cellular thiol anti-oxidants, protecting
      proteins from irreversible oxidative damage. In this study, we found that aldo
      keto reductase family 1 member B10 (AKR1B10) contains 4 Cys residues, i.e.,
      Cys45, Cys187, Cys200, and Cys299. Exposing AKR1B10 to ROS mixtures resulted in
      significant decrease of its free sulfhydryl groups, up to 40-50% in the presence
      of physiological thiol cysteine at 0.5 or 1.0 mM; and accordingly, AKR1B10
      enzymatic activity was reversibly decreased, in parallel with the oxidation of
      the sulfhydryl groups. ROS-induced thiolation also affected the sensitivity of
      AKR1B10 to inhibitors EBPC, epalrestat, and statil. Together our results showed
      for the first time that AKR1B10's enzymatic activity and inhibitor sensitivity
      are modulated by thiol/disulfide exchanges.

PMID- 20144906
TI  - Time-course effects of systemically administered diesel exhaust particles in
      rats.
AB  - Nanosized fraction of particulate air pollution has been reported to translocate
      from the airways into the bloodstream and act on different organs. However, the
      direct effect of these translocated particles is not well understood. In this
      study, we determined the time-course (6 h, 18 h, 48 h and 168 h) effects of the
      systemic administration of 0.02 mg/kg diesel exhaust particles (DEP) on systolic
      blood pressure (SBP), systemic inflammation, oxidative status, and morphological
      alterations in lungs, heart, liver and kidneys in Wistar rats. SBP was
      significantly decreased at 6 h (P < 0.05) but no significant effects have been
      observed at later time points. The leukocyte numbers were increased at 6 h (P <
      0.05) and 18 h (P < 0.05). However, the platelet numbers were significantly
      decreased (P < 0.05) 6 h following the systemic administration of DEP. The IL-6
      concentrations in plasma was increased at 6 h (P < 0.05) and 18 h (P < 0.05).
      Similarly, superoxide dismutase activity was significantly increased at 6 (P =
      0.01) and 18 h (P < 0.05) following DEP exposure. The direct addition of DEP (0.1
      1 microg/ml) to untreated rat blood significantly induced in vitro platelet
      aggregation in a dose-dependent fashion. The activation of intravascular
      coagulation was confirmed by a dose-dependent shortening of activated partial
      thromboplastin time and the prothrombin time following in vitro exposure to DEP
      (0.25-1 microg/ml). Histological analysis revealed the presence of DEP in the
      lungs, heart, liver and kidneys. However, the morphological changes were only
      observed in the lungs, where the presence of infiltration of inflammatory cells
      was observed as early as 6 h, increased at 18 h, and decreased in intensity at 48
      h and at 168 h. We conclude that the direct systemic administration of DEP caused
      acute effect on SBP (6 h) and systemic inflammation and oxidative stress mainly
      at 6 h and 18 h. Despite the presence of DEP in lungs, heart, liver and kidneys,
      the histopathological changes were only seen in the lung which suggests that, at
      the dose and time-points investigated, DEP cause inflammation and have a
      predilection for pulmonary tissue.

PMID- 20144907
TI  - Comparison of preservative-induced toxicity on monolayer and stratified Chang
      conjunctival cells.
AB  - Preservatives are used in ocular medications to prevent microbial contamination.
      The use of benzalkonium chloride (BAC), the most widely used preservative in
      ocular medications, has been scrutinized with a number of studies indicating its
      toxicity to monolayer cultures of corneal and conjunctival epithelial cells. The
      purpose of this study was to evaluate and compare the toxicity of BAC and other
      preservatives and common components of ocular formulations on monolayer and
      stratified air-lifted cultures of Chang conjunctival cells. Air-lifting Chang
      cells grown on transwell filters increased stratification as assessed by
      transepithelial electrical resistance and histology. Unlike monolayer cultures in
      which ocular medications containing BAC caused near complete loss of cell
      viability, stratified, air-lifted cultures were not affected by the presence of
      BAC in ocular medications with up to 30-min exposures. Stratification shifted the
      dose-response curve to the right for benzalkonium chloride, thimerosal,
      chlorhexidine digluconate, potassium sorbate and EDTA. These results demonstrate
      that stratification significantly affects cell viability of Chang conjunctival
      cells in response to preservatives and additives of ophthalmic preparations.

PMID- 20144908
TI  - Comparison of unmobilized and mobilized graft characteristics and the
      implications of cell subsets on autologous and allogeneic transplantation
      outcomes.
AB  - Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) are
      considered the standard of care for many malignancies, including lymphoma,
      myeloma, and some leukemias. In many cases, mobilized peripheral blood has become
      the preferred source of hematopoietic stem cells. The efficacy of different
      mobilization regimens and transplantation outcomes based on cell doses has been
      well studied; however, the characteristics of the stem cell graft may be of equal
      importance with respect to patient outcomes following autologous or allogeneic
      HSCT. This review summarizes available preclinical and clinical data for bone
      marrow and mobilized peripheral blood HSCT characteristics, defined as the cell
      types found in the graft as well as their gene expression profiles. It also
      explores how graft characteristics can affect bone marrow homing, engraftment,
      immune reconstitution, and other posttransplantation outcomes in both the
      allogeneic and autologous HSCT settings.

PMID- 20144910
TI  - The pharyngeal pouches and clefts: Development, evolution, structure and
      derivatives.
AB  - The pharyngeal arches form the face and neck of the developing embryo. The
      pharyngeal tissue is divided into distinct arches by the formation of clefts and
      pouches in between the arches. These clefts and pouches form at the juxtaposition
      between the ectoderm and endoderm and develop into a variety of essential
      structures, such as the ear drum, and glands such as the thymus and parathyroids.
      How these pouches and clefts between the arches form and what structures they
      develop into is the subject of this review. Differences in pouch derivatives are
      described in different animals and the evolution of these structures are
      investigated. The implications of defects in pouch and cleft development on human
      health are also discussed.

PMID- 20144909
TI  - Unrelated transplantation for poor-prognosis adult acute lymphoblastic leukemia:
      long-term outcome analysis and study of the impact of hematopoietic graft source.
AB  - Adults with high-risk acute lymphoblastic leukemia (HR-ALL) have a poor outcome
      with standard chemotherapy and usually undergo unrelated stem cell
      transplantation (SCT) if a matched sibling donor is not available. We analyzed
      the outcome of adult patients with unrelated SCT for HR-ALL and studied the
      possible effect of the hematopoietic stem cell source of the transplant. A total
      of 149 adult patients (median age, 29 years, range, 15-59 years) with HR-ALL
      underwent unrelated SCT in 13 Spanish institutions between 2000 and 2007.
      Patients in first complete remission (CR1) at transplantation had at least one
      adverse prognostic factor (advanced age, adverse cytogenetics, hyperleukocytosis,
      or slow response to induction therapy). ALL was in CR1 in 81 patients (54%), in
      second CR (CR2) in 37 patients (25%), in third CR (CR3) in 11 patients (7%), and
      with overt disease in 20 patients (13%). The hematopoietic source was unrelated
      cord blood (UCB) in 62 patients and an unrelated donor (UD) in 87 patients. The
      patients undergoing UCB-SCT and UD-SCT were comparable in terms of the main
      clinical and biological features of ALL, except for a higher frequency of
      patients with more overt disease in the UCB-SCT group. There was no statistically
      significant difference in overall survival (OS) or disease-free survival (DFS) at
      5 years between the 2 groups. Treatment-related mortality (TRM) was significantly
      lower in the UCB-SCT group (P = .021). The probability of relapse at 1 year was
      17% (95% confidence interval [CI], 7%-27%) for the UD-SCT group and 27% (95% CI,
      14%-40%) for the UCB-SCT group (P = .088), respectively. Only disease status at
      transplantation (CR1, 41% [95% CI, 18%-64%] vs CR2, 51% [95% CI, 17%-85%] vs
      advanced disease, 66% [95% CI, 46%-86%]; P = .001) and the absence of chronic
      graft-versus-host disease (74% [95% CI, 46%-100%] vs 33% [95% CI, 17%-49%]; P =
      .034) were significant factors for relapse. All unrelated transplantation
      modalities were associated with high treatment-related mortality for adult HR-ALL
      patients without a sibling donor. UCB-SCT and UD-SCT were found to be equivalent
      options. Disease status at transplantation and chronic GVHD were the main factors
      influencing relapse in both transplantation modalities.

PMID- 20144911
TI  - Pathways: Strategies for susceptibility genes in SLE.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disorder marked by an
      inappropriate immune response to nuclear antigens. Recent whole genome
      association and more focused studies have revealed numerous genes implicated in
      this disease process, including ITGAM, Fc gamma receptors, complement components,
      C-reactive protein, and others. One common feature of these molecules is their
      involvement in the immune opsonin pathway and in phagocytic clearing of nuclear
      antigens and apoptotic debris, which provide excessive exposure of lupus-related
      antigens to immune cells. Analysis of gene-gene interactions in the opsonin
      pathway and its relationship to SLE may provide a system-based approach to
      identify additional candidate genes associated with disease able to account for a
      larger part of lupus susceptibility.

PMID- 20144912
TI  - Genetic and hormonal factors in female-biased autoimmunity.
AB  - Autoimmunity is controlled both by the environment and by genetic factors. One of
      the most well defined genetic factors is polymorphisms, with some alleles of
      particular genes promoting autoimmune diseases, whereas other alleles either not
      affecting susceptibility to disease or, in some cases actually inhibiting the
      appearance of such illnesses. Another genetically controlled factor, gender, also
      plays a profound role in the incidence of autoimmune diseases. For example,
      Systemic Lupus Erythematosus (SLE) occurs much more frequently in females than in
      males in both mice and man. The genetic differences that make some individuals
      susceptible to autoimmunity and protect others could act in many ways and affect
      many tissues. In this review we will discuss how gender may act on the cells of
      the immune system and thereby influence the predisposition of the host to
      autoimmune diseases.

PMID- 20144913
TI  - Influence of polymer content in Ca-deficient hydroxyapatite-polycaprolactone
      nanocomposites on the formation of microvessel-like structures.
AB  - Calcium phosphate (CaP) ceramics are widely used in bone tissue engineering due
      to their good osteoconductivity. The mechanical properties of CaP can be modified
      by the addition of small volume fractions of biodegradable polymers such as
      polycaprolactone (PCL). Nevertheless, it is also important to evaluate how the
      polymer content influences cell-material or cell-cell interactions because of
      potential consequences for bone regeneration and vascularization. In this study
      we assessed the general biocompatibilty of Ca-deficient hydroxyapatite (CDHA)-PCL
      disks containing nominally 11 and 24% polycaprolactone using human umbilical vein
      endothelial cells and human primary osteoblasts. Confocal microscopy showed that
      both CDHA-PCL variants supported the growth of both cell types. In terms of the
      endothelial cells grown on CDHA-PCL nanocomposites with 24% PCL, an increased
      expression of the endothelial marker vWF compared to CDHA-PCL with 11% PCL was
      observed in real-time polymerase chain reaction analysis. In addition to
      monocultures, co-cultures of outgrowth endothelial cells, derived from peripheral
      blood, and primary osteoblasts were assessed as an example of a more complex test
      system for bone regeneration and vascularization. Constructs based on CDHA with
      different PCL contents were investigated with regard to the formation of
      microvessel-like structures induced by the co-culture process using confocal
      microscopy and quantitative image analysis. Furthermore, the osteogenic
      differentiation of the co-culture was assessed. As a result, more pre-vascular
      structures were observed after 1 week on the CDHA-PCL disks with 24% PCL, whereas
      after 4 weeks of culture the extent of microvessel-like structure formation was
      slightly higher on the CDHA with 11% PCL. In contrast to this, variation of PCL
      content had no effect on the osteogenic differentiation in the co-culture.

PMID- 20144915
TI  - Calcium alginate microcapsules with spherical liquid cores templated by gelatin
      microparticles for mass production of multicellular spheroids.
AB  - Multicellular spheroids are important in biomedical applications, such as drug
      research and regenerative medicine. We developed microcapsules from sodium
      alginate and gelatin for mass production of size-controlled spheroids with
      diameters <200 microm. The microcapsules were composed of calcium alginate gels
      with spherical liquid cores (diameter approximately 150 microm) for formation of
      spheroids. The spherical liquid cores were prepared by incubating calcium
      alginate microcapsules containing thermally gelled, cell-enclosing gelatin
      microparticles about 150 microm in diameter, at 37 degrees C. The gelatin
      microparticles were encapsulated within the microcapsules by dropping a sodium
      alginate solution containing suspended gelatin microparticles into 100 mM
      CaCl(2). The enclosed feline renal fibroblast cell line, CRFK, cells showed 93.8%
      viability immediately after encapsulation, then grew and completely filled the
      spherical cores. Multicellular spheroids were collected within 1 min by soaking
      microcapsules in a medium containing alginate lyase.

PMID- 20144914
TI  - Mechanical and microstructural properties of polycaprolactone scaffolds with one
      dimensional, two-dimensional, and three-dimensional orthogonally oriented porous
      architectures produced by selective laser sintering.
AB  - This article reports on the experimental determination and finite element
      modeling of tensile and compressive mechanical properties of solid
      polycaprolactone (PCL) and of porous PCL scaffolds with one-dimensional, two
      dimensional and three-dimensional orthogonal, periodic porous architectures
      produced by selective laser sintering (SLS). PCL scaffolds were built using
      optimum processing parameters, ensuring scaffolds with nearly full density (>95%)
      in the designed solid regions and with excellent geometric and dimensional
      control (within 3-8% of design). The tensile strength of bulk PCL ranged from
      10.5 to 16.1 MPa, its modulus ranged from 343.9 to 364.3 MPa, and the tensile
      yield strength ranged from 8.2 to 10.1 MPa. These values are consistent with
      reported literature values for PCL processed through various manufacturing
      methods. Across porosity ranged from 56.87% to 83.3%, the tensile strength ranged
      from 4.5 to 1.1 MPa, the tensile modulus ranged from 140.5 to 35.5 MPa, and the
      yield strength ranged from 3.2 to 0.76 MPa. The compressive strength of bulk PCL
      was 38.7 MPa, the compressive modulus ranged from 297.8 to 317.1 MPa, and the
      compressive yield strength ranged from 10.3 to 12.5 MPa. Across porosity ranged
      from 51.1% to 80.9%, the compressive strength ranged from 10.0 to 0.6 MPa, the
      compressive modulus ranged from 14.9 to 12.1 MPa, and the compressive yield
      strength ranged from 4.25 to 0.42 MPa. These values, while being in the lower
      range of reported values for trabecular bone, are the highest reported for PCL
      scaffolds produced by SLS and are among the highest reported for similar PCL
      scaffolds produced through other layered manufacturing techniques. Finite element
      analysis showed good agreement between experimental and computed effective
      tensile and compressive moduli. Thus, the construction of bone tissue engineering
      scaffolds endowed with oriented porous architectures and with predictable
      mechanical properties through SLS is demonstrated.

PMID- 20144917
TI  - Conic section function neural network circuitry for offline signature
      recognition.
AB  - In this brief, conic section function neural network (CSFNN) circuitry was
      designed for offline signature recognition. CSFNN is a unified framework for
      multilayer perceptron (MLP) and radial basis function (RBF) networks to make
      simultaneous use of advantages of both. The CSFNN circuitry architecture was
      developed using a mixed mode circuit implementation. The designed circuit system
      is problem independent. Hence, the general purpose neural network circuit system
      could be applied to various pattern recognition problems with different network
      sizes on condition with the maximum network size of 16-16-8. In this brief, CSFNN
      circuitry system has been applied to two different signature recognition
      problems. CSFNN circuitry was trained with chip-in-the-loop learning technique in
      order to compensate typical analog process variations. CSFNN hardware achieved
      highly comparable computational performances with CSFNN software for nonlinear
      signature recognition problems.

PMID- 20144918
TI  - Penalized preimage learning in kernel principal component analysis.
AB  - Finding the preimage of a feature vector in kernel principal component analysis
      (KPCA) is of crucial importance when KPCA is applied in some applications such as
      image preprocessing. Since the exact preimage of a feature vector in the kernel
      feature space, normally, does not exist in the input data space, an approximate
      preimage is learned and encouraging results have been reported in the last few
      years. However, it is still difficult to find a "good" estimation of preimage. As
      estimation of preimage in kernel methods is ill-posed, how to guide the preimage
      learning for a better estimation is important and still an open problem. To
      address this problem, a penalized strategy is developed in this paper, where some
      penalization terms are used to guide the preimage learning process. To develop an
      efficient penalized technique, we first propose a two-step general framework, in
      which a preimage is directly modeled by weighted combination of the observed
      samples and the weights are learned by some optimization function subject to
      certain constraints. Compared to existing techniques, this would also give
      advantages in directly turning preimage learning into the optimization of the
      combination weights. Under this framework, a penalized methodology is developed
      by integrating two types of penalizations. First, to ensure learning a well
      defined preimage, of which each entry is not out of data range, convexity
      constraint is imposed for learning the combination weights. More insight effects
      of the convexity constraint are also explored. Second, a penalized function is
      integrated as part of the optimization function to guide the preimage learning
      process. Particularly, the weakly supervised penalty is proposed, discussed, and
      extensively evaluated along with Laplacian penalty and ridge penalty. It could be
      further interpreted that the learned preimage can preserve some kind of pointwise
      conditional mutual information. Finally, KPCA with preimage learning is applied
      on face image data sets in the aspects of facial expression normalization, face
      image denoising, recovery of missing parts from occlusion, and illumination
      normalization. Experimental results show that the proposed preimage learning
      algorithm obtains lower mean square error (MSE) and better visual quality of
      reconstructed images.

PMID- 20144919
TI  - Advanced Hough transform using a multilayer fractional Fourier method.
AB  - The Hough transform (HT) is a commonly used technique for the identification of
      straight lines in an image. The Hough transform can be equivalently computed
      using the Radon transform (RT), by performing line detection in the frequency
      domain through use of central-slice theorem. In this research, an advanced Radon
      transform is developed using a multilayer fractional Fourier transform, a
      Cartesian-to-polar mapping, and 1-D inverse Fourier transforms, followed by peak
      detection in the sinogram. The multilayer fractional Fourier transform achieves a
      more accurate sampling in the frequency domain, and requires no zero padding at
      the stage of Cartesian-to-polar coordinate mapping. Our experiments were
      conducted on mix-shape images, noisy images, mixed-thickness lines and a large
      data set consisting of 751,000 handwritten Chinese characters. The experimental
      results have shown that our proposed method outperforms all known representative
      line detection methods based on the standard Hough transform or the Fourier
      transform.

PMID- 20144920
TI  - A monocular marker-free gait measurement system.
AB  - This paper presents a new, user-friendly, portable motion capture and gait
      analysis system for capturing and analyzing human gait, designed as a
      telemedicine tool to monitor remotely the progress of patients through treatment.
      The system requires minimal user input and simple single-camera filming (which
      can be acquired from a basic webcam) making it very accessible to nontechnical,
      nonclinical personnel. This system can allow gait studies to acquire a much
      larger data set and allow trained gait analysts to focus their skills on the
      interpretation phase of gait analysis. The design uses a novel motion capture
      method derived from spatiotemporal segmentation and model-based tracking. Testing
      is performed on four monocular, sagittal-view, sample gait videos. Results of
      modeling, tracking, and analysis stages are presented with standard gait graphs
      and parameters compared to manually acquired data.

PMID- 20144921
TI  - Experimental analysis of accuracy in the identification of motor unit spike
      trains from high-density surface EMG.
AB  - The aim of this study was to compare the decomposition results obtained from high
      density surface electromyography (EMG) and concurrently recorded intramuscular
      EMG. Surface EMG signals were recorded with electrode grids from the tibialis
      anterior, biceps brachii, and abductor digiti minimi muscles of twelve healthy
      men during isometric contractions ranging between 5% and 20% of the maximal
      force. Bipolar intramuscular EMG signals were recorded with pairs of wire
      electrodes. Surface and intramuscular EMG were independently decomposed into
      motor unit spike trains. When averaged over all the contractions of the same
      contraction force, the percentage of discharge times of motor units identified by
      both decompositions varied in the ranges 84%-87% (tibialis anterior), 84%-86%
      (biceps brachii), and 87%-92% (abductor digiti minimi) across the force levels
      analyzed. This index of agreement between the two decompositions was linearly
      correlated with a self-consistency measure of motor unit discharge pattern that
      was based on coefficient of variation for the interspike interval (R(2) = 0.68
      for tibialis anterior, R(2) = 0.56 for biceps brachii, and R(2) = 0.38 for
      abductor digiti minimi). These results constitute an important contribution to
      the validation of the noninvasive approach for the investigation of motor unit
      behavior in isometric low-force tasks.

PMID- 20144923
TI  - Self-paced operation of an SSVEP-Based orthosis with and without an imagery-based
      "brain switch:" a feasibility study towards a hybrid BCI.
AB  - This work introduces a hybrid brain-computer interface (BCI) composed of an
      imagery-based brain switch and a steady-state visual evoked potential (SSVEP)
      based BCI. The brain switch (event related synchronization (ERS)-based BCI) was
      used to activate the four-step SSVEP-based orthosis (via gazing at a 8 Hz LED to
      open and gazing at a 13 Hz LED to close) only when needed for control, and to
      deactivate the LEDs during resting periods. Only two EEG channels were required,
      one over the motor cortex and one over the visual cortex. As a basis for
      comparison, the orthosis was also operated without using the brain switch. Six
      subjects participated in this study. This combination of two BCIs operated with
      different mental strategies is one example of a "hybrid" BCI and revealed a much
      lower rate of FPs per minute during resting periods or breaks compared to the
      SSVEP BCI alone ( FP=1.46+/-1.18 versus 5.40 +/- 0.90). Four out of the six
      subjects succeeded in operating the self-paced hybrid BCI with a good performance
      (positive prediction value PPVb > 0.70).

PMID- 20144922
TI  - Development of closed-loop neural interface technology in a rat model: combining
      motor cortex operant conditioning with visual cortex microstimulation.
AB  - Closed-loop neural interface technology that combines neural ensemble decoding
      with simultaneous electrical microstimulation feedback is hypothesized to improve
      deep brain stimulation techniques, neuromotor prosthetic applications, and
      epilepsy treatment. Here we describe our iterative results in a rat model of a
      sensory and motor neurophysiological feedback control system. Three rats were
      chronically implanted with microelectrode arrays in both the motor and visual
      cortices. The rats were subsequently trained over a period of weeks to modulate
      their motor cortex ensemble unit activity upon delivery of intra-cortical
      microstimulation (ICMS) of the visual cortex in order to receive a food reward.
      Rats were given continuous feedback via visual cortex ICMS during the response
      periods that was representative of the motor cortex ensemble dynamics. Analysis
      revealed that the feedback provided the animals with indicators of the behavioral
      trials. At the hardware level, this preparation provides a tractable test model
      for improving the technology of closed-loop neural devices.

PMID- 20144924
TI  - 6-benzyladenine metabolism during reinvigoration of mature Pinus radiata buds in
      vitro.
AB  - Maturation or phase change is a serious challenge in the deployment of superior
      trees of Pinus radiata D. Don because of the difficulties associated with
      propagation of cuttings from mature trees. We used an in vitro system to study 6
      benzyladenine (BA)-induced reinvigoration of the fascicle meristems of mature
      buds during in vitro culture. Anatomical examinations revealed that BA inhibited
      the development of secondary needle primordia and 'rejuvenated' the fascicle
      meristems of the mature bud to produce primary needles, which are characteristic
      of the juvenile phase in P. radiata. Without BA supplement in the culture media,
      fascicle primordia continued developing secondary needles and quiescent fascicle
      meristems. BA metabolite analysis showed that the novel cytokinin pathway
      reported previously in P. radiata (H. Zhang, K.J. Horgan, P.H.S. Reynolds, G.E.
      Norris and P.E. Jameson. 2001. Novel cytokinins: The predominant forms in mature
      buds of Pinus radiata. Physiol. Plant. 112: 127-134) was mirrored in vitro, with
      BA converted into a variety of metabolites including 6-benzylamino-9
      glucopyranosylribosyl-purine and its novel phosphorylated form, 6-benzylamino-9
      glucopyranosylribosyl-purine. The culture of mature buds in the presence of BA
      caused a reduction in the level of endogenous cytokinins, suggesting a direct
      action of BA itself. Similar correlations are noted between levels of certain
      metabolites and the maturation status of buds from field-grown trees and buds in
      culture, indicating that this in vitro system may be a good model for studying
      the processes of maturation and reinvigoration.

PMID- 20144925
TI  - Ecosystem warming does not affect photosynthesis or aboveground autotrophic
      respiration for boreal black spruce.
AB  - We measured light-saturated photosynthesis (A(net)), foliage respiration (R(fol))
      and stem respiration (R(stem)) of black spruce (Picea mariana (Mill.) B.S.P.) in
      heated (+5 degrees C) and control plots during 2005, 2006 and 2007 in Thompson,
      MB, Canada. Large greenhouses and soil-heating cables were used to maintain air
      and soil temperature 5 degrees C above ambient air and soil temperature. Each
      greenhouse contained approximately nine black spruce trees and the majority of
      their fine root mass. Treatments were soil and air warming, soil-only warming,
      greenhouses maintained at ambient air temperature and control. Gas exchange rates
      ranged 0.71-4.66, 0.04-0.74 and 0.1-1.0 micromol m(-)(2) s(-)(1) for A(net),
      R(fol) and R(stem), respectively. Treatment differences for A(net), R(fol) and
      R(stem) were not significant in any of the 3 years of measurements. The results
      of this experiment suggest that in a warmer climate, black spruce may not have
      significant changes in the rate of photosynthesis or respiration.

PMID- 20144926
TI  - Tendon friction rubs in early diffuse systemic sclerosis: prevalence,
      characteristics and longitudinal changes in a randomized controlled trial.
AB  - OBJECTIVES: To characterize the baseline tendon friction rubs (TFRs) in early
      dcSSc and to evaluate the association of change in TFR over 6 and 12 months with
      changes in modified Rodnan skin score (MRSS) and HAQ-Disability Index (HAQ-DI)
      over 12 and 24 months, respectively. METHODS: We analysed data from the d-Pen
      study, a 2-year study in early dcSSc (< or =18 months from first non-Raynaud's
      symptom). TFR was scored as present/absent at seven anatomical sites at baseline
      and every 6 months thereafter. Multivariable linear regression models assessed
      associations between TFR and change in MRSS, and change in the HAQ-DI, over 12
      and 24 months, respectively. Covariates included baseline TFR, change in the TFR
      over 6 and 12 months, age, sex, duration of SSc, MRSS, and tender joint count and
      swollen joint count (SJC). RESULTS: Forty-nine (37%) of 134 patients had TFR at
      baseline, 50% had resolution of their TFR, whereas 21% developed new TFRs.
      Patients with baseline TFRs were likely to be Caucasian (86 vs 58%) and had a
      higher HAQ-DI score (P = 0.008). In regression analyses, change in TFR (P = 0.04)
      and baseline MRSS (P = 0.03) predicted change in MRSS over a 12-month period
      (Model R(2 )= 0.14). For the HAQ-DI model, independent predictors were change in
      TFR at 6 months (P = 0.008) and baseline SJC (P = 0.04, Model R(2 )= 0.19).
      Results were similar for 24-month models. CONCLUSIONS: We document the presence
      of TFR very early in the course of dcSSc. Changes in TFR over 6 and 12 months
      predict changes in MRSS and HAQ-DI over 12 and 24 months, respectively.

PMID- 20144927
TI  - Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for
      disease activity in lupus nephritis.
AB  - OBJECTIVES: Clinical and laboratory markers in current use have limited
      specificity and sensitivity for predicting the development of renal disease in
      lupus patients. In this longitudinal study, we investigated whether urinary
      neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and
      renal flares in lupus patients with and without a history of biopsy-proven lupus
      nephritis. METHODS: Renal disease activity and flare status was determined by
      SLEDAI and BILAG scores. Random effects models were used to determine whether
      uNGAL was a significant predictor for renal disease activity in SLE patients, and
      for renal flares in patients with established nephritis. To assess the predictive
      performance of uNGAL, receiver operating characteristic (ROC) curves were
      constructed using the previous visit's uNGAL level. These curves were then
      compared with curves constructed with currently used biomarkers. Cut-offs
      determined by ROC curves were tested in an independent validation cohort.
      RESULTS: uNGAL was found to be a significant predictor of renal disease activity
      in all SLE patients, and a significant predictor for flare in patients with a
      history of biopsy-proven nephritis, in multivariate models adjusting for age,
      race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of
      renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti
      dsDNA antibody titres. These results were confirmed in an independent validation
      cohort. CONCLUSIONS: uNGAL predicts renal flare in patients with a history of
      biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL
      is a more sensitive and specific forecaster of renal flare in patients with a
      history of lupus nephritis than anti-dsDNA antibody titres.

PMID- 20144928
TI  - The danger model in deciphering autoimmunity.
AB  - Autoimmunity has been a topic of intensive research for several decades, yet
      amazingly, no uniform hypothesis exists to explain the basis for the spectrum of
      autoantibody specificities seen in autoimmune diseases. It therefore seems
      appropriate to consider whether our current framework for understanding
      tolerance, and thus the mechanisms controlling the initiation and perpetuation of
      autoimmunity, may be faulty. Adapting the paradigm of Matzinger-the 'danger
      model', a case can be made for a perspective that appreciates the fundamental
      role of the tissues in controlling immune response, favouring a shift of focus in
      studies on the initiation of autoimmunity. Applying the elements of this model, I
      set forth a number of scenarios for how autoreactivity could emerge, with
      emphasis on the likely sources of the involved autoantigens and the functional
      basis of their appearance. The emerging picture is one in which disruption of
      tissue homeostasis takes centre stage, with the antigen-presenting cells as the
      key players.

PMID- 20144929
TI  - HRCT-proven leflunomide pneumonitis in a patient with psoriatic arthritis and
      normal lung function tests and chest radiography.

PMID- 20144930
TI  - Pulmonary arterial hypertension associated with systemic sclerosis in patients
      with functional class II dyspnoea: mild symptoms but severe outcome.
AB  - OBJECTIVE: To describe the history of SSc-associated pulmonary arterial
      hypertension (SSc-PAH) in patients with New York Heart Association (NYHA)
      functional class (FC) II dyspnoea at diagnosis. METHODS: Data at the time of
      diagnosis were collected and analysed retrospectively for 77 consecutive patients
      with SSc-PAH. RESULTS: Twelve patients (15.6%) presented with PAH and NYHA FC II
      dyspnoea. After a mean follow-up of 44 months, only 4 out of the 12 PAH patients
      remained stable in FC II, while 8 showed worsening to FC III or IV. Three
      patients died during the observation period; two from PAH and one from rectal
      cancer. Survival in patients in FC II at diagnosis was 100, 91 and 80% at 1, 2
      and 3 years, respectively. CONCLUSIONS: A majority of patients with mildly
      symptomatic SSc-PAH in NYHA FC II at diagnosis have a severe disease with poor
      prognosis.

PMID- 20144931
TI  - The burden of wait for knee replacement surgery: effects on pain, function and
      health-related quality of life at the time of surgery.
AB  - OBJECTIVE: To examine the change in pain and function related to the knee
      scheduled for surgery, change in health-related quality of life (HRQoL) and
      change in contralateral knee pain during pre-surgery wait up until time of
      surgery. METHODS: One hundred and fifty-three patients scheduled for knee
      replacement were recruited from three hospitals in Quebec City, Canada, and
      followed until surgery. Pre-surgery wait, defined as the time between enrolment
      on the pre-surgery wait list and surgery, was considered in five categories (< or
      =3, >3-6, >6-9, >9-12 and >12 months). Pain and functional limitations were
      measured with the Western Ontario and McMaster Osteoarthritis Index (WOMAC) and
      HRQoL was measured with the medical outcomes study 36-item short form health
      survey. RESULTS: Mean pre-surgery wait time was 183 (s.d. 121.9) days. Subjects
      having waited >9-12 months showed significant deterioration of the WOMAC pain (
      9.9; 95% CI -19.2, -0.54) and function (-11.1; 95% CI -18.7, -3.4) scores. On the
      HRQoL SF-36 physical functioning scale, a significant deterioration was seen in
      subjects having waited >9-12 months (-11.3; 95% CI -18.4, -4.2) and >12 months (
      7.1; 95% CI -12.9, -1.3). On the contralateral knee WOMAC pain score, a
      significant deterioration was observed in subjects having waited >6-9 months (
      10.4; 95% CI -16.9, -3.9) and >12 months (-10.7; 95% CI -19.7, -1.7). CONCLUSION:
      Pre-surgery wait time has a negative significant impact on pain, function and
      HRQoL at the time of surgery. The magnitude of deterioration seen in this study
      may be clinically important. The effects of this pre-surgery deterioration on
      post-surgery outcomes need to be investigated.

PMID- 20144932
TI  - Therapeutic efficacy and effect on gametocyte carriage of an artemisinin and a
      non-based combination treatment in children with uncomplicated P. falciparum
      malaria, living in an area with high-level chloroquine resistance.
AB  - Combination therapy with artemesinin or non-artemesinin-based antimalarials (ACTs
      or NACTs) are known to retard the development and progression of drug resistance
      in Plasmodium falciparum (P. falciparum). The optimal antimalarial combinations
      in Africa are yet unknown. We evaluate the therapeutic efficacy and effects on
      gametocyte carriage of Artemether-Lumefantrine (AL) and Amodiaquine
      Sulfalene/Pyrimethamine (ASP) in children with P. falciparum malaria in an
      endemic area. One-hundred and thirty-nine children aged <= 10 years with
      uncomplicated P. falciparum malaria were enrolled. The primary end points were
      adequate clinical and parasitological response (ACPR), late parasitological
      failure(LPF), late clinical failure (LCF) and early treatment failure (ETF).
      Polymerase chain reaction (PCR)-corrected cure rates on days 14-42 and gametocyte
      carriage rates were determined. Fever clearance time was significantly shorter (P
      = 0.009) with ASP, but parasite clearance time was similar with both regimens.
      Day 28 cure rates were 91.4 and 89.9% (PCR-corrected) for AL and ASP
      respectively. Both regimens were well tolerated. Overall, gametocyte carriage
      before and following treatment were similar. Both combinations were found
      effective and comparable for treatment of acute, uncomplicated, P. falciparum
      malaria.

PMID- 20144933
TI  - Clinical signs predicting severe illness in young infants (<60 days) in Bolivia.
AB  - Identification of simple signs and symptoms that predict severe illness needing
      referral for admission of young infants is critical for reducing mortality in
      developing countries. Infants <2 months of age presenting to two hospitals in La
      Paz, Bolivia (n=1082) were evaluated by nurses for signs and symptoms, and
      independently by physicians for the need for admission. In young neonates,
      sensitivity of individual clinical signs was >35% for measured temperature >=
      37.5 degrees  C (65%); all signs had specificity >85%. Odds ratios (ORs) for
      association of individual clinical signs with need for urgent hospital management
      were highest (>5) for history of difficulty feeding, not feeding well and fever.
      Clinical signs or symptoms are useful for primary healthcare workers to identify
      young infants with serious illness needing admission, and have been incorporated
      into the Integrated Management of Childhood Illness algorithm for use in Bolivia
      and elsewhere in Latin America.

PMID- 20144934
TI  - Oral artesunate for neonatal malaria.
AB  - A 24-day male baby presented with a history of fever and poor feeding. The baby
      was pale and had hepatosplenomegaly. Peripheral blood films revealed Plasmodium
      vivax. Chloroquine is the drug of choice in neonatal malaria. However, our
      patient did not respond to chloroquine. There has been very little experience
      with other drugs. This case highlights the use of oral artesunate to which the
      baby responded. The future may see its more frequent use in resistant malaria.

PMID- 20144935
TI  - Delivering comprehensive home-based care programmes for HIV: a review of lessons
      learned and challenges ahead in the era of antiretroviral therapy.
AB  - Home-based care (HBC) programmes in low- and middle-income countries have evolved
      over the course of the past two decades in response to the HIV epidemic and wider
      availability of antiretroviral therapy (ART). Evidence is emerging from small
      scale and well-resourced studies that ART delivery can be effectively
      incorporated within HBC programmes. However, before this approach can be
      expanded, it is necessary to consider the lessons learned from implementing
      routine HBC programmes and to assess what conditions are required for their roll
      out in the context of ART provision. In this paper, we review the literature on
      existing HBC programmes and consider the arguments for their expansion in the
      context of scaling up ART delivery. We develop a framework that draws on the
      underlying rationale for HBC and incorporates lessons learned from community
      health worker programmes. We then apply this framework to assess whether the
      necessary conditions are in place to effectively scale up HBC programmes in the
      ART era. We show that the most effective HBC programmes incorporate ongoing
      support, training and remuneration for their workers; are integrated into
      existing health systems; and involve local communities from the outset in
      programme planning and delivery. Although considerable commitment has so far been
      demonstrated to delivering comprehensive HBC programmes, their effectiveness is
      often hindered by weak linkages with other HIV services. Top-down donor policies
      and a lack of sustainable and consistent funding strategies represent a
      formidable threat to these programmes in the long term. The benefits of HBC
      programmes that incorporate ART care are unlikely to be replicated on a larger
      scale unless donors and policymakers address issues related to human resources,
      health service linkages and community preparedness. Innovative and sustainable
      funding policies are needed to support HBC programmes if they are to effectively
      complement national ART programmes in the long term.

PMID- 20144936
TI  - Why do health systems matter? Exploring links between health systems and HIV
      response: a case study from Russia.
AB  - INTRODUCTION: Studies on the relevance of stronger health systems to the success
      of vertical programmes has focused mainly on developing countries with fragile
      infrastructures and limited human resources. Research in middle-income, and
      particularly post-Soviet, settings has been scarce. This article examines the
      relationships between health system characteristics and the HIV response in
      Russia, the country which towards the end of the Soviet period had the world's
      highest ratios of doctors and hospital beds to population and yet struggled to
      address the growing threat of HIV/AIDS. METHODS: The study is based on semi
      structured qualitative interviews with policy-makers and senior health care
      managers in two Russian regions, and a review of published and unpublished
      sources on health systems and HIV in Russia. FINDINGS: We identified a number of
      factors associated with the system's failure to address the epidemic. We argue
      that these factors are not unique to HIV/AIDS. The features of the wider health
      system within which the HIV response was set up influenced the structure and
      capacities of the programme, particularly its regulatory and clinical
      orientation; the discrepancy between formal commitments and implementation; the
      focus on screening services; and problems with scaling up interventions targeting
      high-risk groups. DISCUSSION: The system-programme interplay is as important in
      middle-income countries as in poorer settings. An advanced health care
      infrastructure cannot protect health systems from potential failures in the
      delivery of vertical programmes. The HIV response cannot be effective, efficient
      and responsive to the needs of the population if the broader health system does
      not adhere to the same principles. Strengthening HIV responses in post-Soviet
      societies will require improvements in their wider health systems, namely
      advocacy of prevention for high-risk populations, reallocation of resources from
      curative towards preventive services, building decision-making capacities at the
      local level, and developing better working environments for health care staff.

PMID- 20144937
TI  - Non-medical sex selection: ethical issues.
AB  - INTRODUCTION: This paper aims to provide a concise review of the ethical issues
      that are commonly raised in the UK debate on non-medical sex selection.
      Background information on sex selection technologies is provided, as is a
      description of the relevant UK legislation. Arguments for and against non-medical
      sex selection will be explained and compared and conclusions will be drawn. It is
      finally suggested that the international debate on non-medical sex selection
      ought to be regarded as an important area of related interest. SOURCES OF DATA:
      Data were obtained from a search of existing ethics and policy literature
      focusing on sex selection. AREAS OF AGREEMENT: There are very few areas of
      universal agreement in the debate. AREAS OF CONTROVERSY: There is much
      disagreement between critics over what harms are likely to be caused by sex
      selection and whether such harms are morally significant. The issue of whether
      governments can legitimately place limitations upon individual reproductive
      autonomy, and if so, to what degree, remains controversial.

PMID- 20144938
TI  - Management of essential hypertension.
AB  - INTRODUCTION: Epidemiological studies have unequivocally shown that hypertension
      (HT)is a major cardiovascular (CV) risk factor and that a direct linear
      relationship exists between the severity of the blood pressure (BP) elevation and
      the occurrence of CV events. AREAS OF AGREEMENT AND CONTROVERSY: The beneficial
      effects of the BP-lowering interventions have been recognized since a number of
      years. These include not only the reduction in CV morbidity and mortality but
      also the regression (or the delay of progression) of HT-related end-organ damage,
      such as left ventricular hypertrophy, vascular remodelling, endothelial
      dysfunction and renal damage. Along with these well-established features,
      antihypertensive drug treatment still faces a number of unmet goals and
      unanswered questions, such as the target BP values to achieve in high-risk
      patients, the threshold of treatment in low-risk patients as well as the choice
      of the therapeutic approach more likely to offer greater CV protection.
      CONCLUSION: Despite unmet goals, antihypertensive treatment has provided
      throughout the years successful results. Future efforts will be need to achieve a
      better BP control in the population and thus to obtain a greater CV protection.

PMID- 20144939
TI  - Living-donor liver transplantation in adults.
AB  - INTRODUCTION: The technique of paediatric living-donor liver transplantation
      (LDLT) has become standardized. In adults, however, there is scope for
      innovation. Unlike cadaveric whole-size liver transplantation and paediatric
      LDLT, size matching between the liver graft and the recipient by body weight has
      been a major challenge in adult LDLT because it is important to provide an
      adequate graft mass to the recipient while leaving a sufficient mass of remnant
      liver in the donor to ensure donor safety. GROWING POINTS: In adult LDLT, liver
      grafts have been selected to meet graft-recipient size-matching requirements. In
      1996, the Hong Kong group pioneered the use of the right-lobe grafts vein to
      overcome the volume insufficiency often encountered with the left-lobe liver
      grafts. Subsequently, the Asan group introduced modified right-lobe grafting with
      interposition vein grafts to drain the venous outflow of the anterior sector,
      thus increasing the functioning hepatocyte mass, and this group initiated dual
      left-lobe liver grafts to overcome both donor risk and volume insufficiency.
      AREAS OF AGREEMENT AND CONTROVERSY: Although the surgical procedures for both
      donors and recipients are more complex for adult LDLT than for whole-organ
      deceased donor transplantation, the outcomes in large-volume centers are now
      similar. Accordingly, the indications for adult LDLT are continually being
      expanded. AREAS TIMELY FOR DEVELOPING RESEARCH: In performing these procedures,
      it is crucial to minimize the risks of morbidity and mortality to the healthy
      live donor. This review focuses on the current technical development and
      discusses the ethical issues of adult LDLT.

PMID- 20144940
TI  - Brief report: Predictors of optimal HIV appointment adherence in minority youth:
      a prospective study.
AB  - OBJECTIVE: This study investigated motivation to attend appointments, self
      efficacy, self-esteem, substance use, and emotional distress as predictors of
      optimal HIV appointment adherence in minority youth living with HIV. METHODS:
      Utilizing a prospective design, questionnaires were collected from 82 minority
      youth (mean age = 20.3) at baseline and appointment adherence was assessed over
      the subsequent 12-month period. Appointment adherence was dichotomized to reflect
      optimal (i.e., at least one appointment in each of the four quarters) versus
      suboptimal appointment adherence (i.e., no appointment in at least one of the
      four quarters). RESULTS: High levels of motivation to attend appointments, high
      levels of self-efficacy, and low levels of alcohol use were associated with
      optimal HIV appointment adherence. CONCLUSIONS: Interventions promoting
      motivation and self-efficacy, while addressing alcohol use and awareness of
      appointment adherence may be promising in improving optimal HIV appointment
      adherence in minority youth.

PMID- 20144941
TI  - There's no place like home: research, practice and policy perspectives regarding
      safety in homecare.

PMID- 20144942
TI  - The association between body mass index and patients' experiences with inpatient
      care.
AB  - OBJECTIVE: To explore the association between patients' body mass index (BMI) and
      their experiences with inpatient care. DESIGN: Cross-sectional. Mail survey.
      SETTING: University Hospital of Geneva. PARTICIPANTS: Questionnaires were mailed
      to 2385 eligible adult patients, 6 weeks after discharge (response rate = 69%).
      MAIN OUTCOME MEASURES: Patients' experiences with care were measured using the
      Picker inpatient survey questionnaire. BMI was calculated using self-reported
      height and weight. Main dependent variables were the global Picker patient
      experience (PPE-15) score and nine dimension-specific problem scores, scored from
      0 (no reported problems) to 1 (all items coded as problems). We used linear
      regressions, adjusting for age, gender, education, subjective health, smoking and
      hospitalization, to assess the association between patients' BMI and their
      experiences with inpatient care. RESULTS: Of the patients, 4.8% were underweight,
      50.8% had normal weight, 30.3% were overweight and 14.1% were obese. Adjusted
      analysis shows that compared with normal weight, obesity was significantly
      associated with fewer problematic items in the surgery-related information
      domain, and being underweight or overweight was associated with more problematic
      items in the involvement of family/friends domain. The global PPE-15 score was
      significantly higher (more problems) for underweight patients. CONCLUSIONS:
      Underweight patients, but not obese patients, reported more problems during
      hospitalization.

PMID- 20144943
TI  - Patient experience data in practice accreditation--an international comparison.
AB  - OBJECTIVE: Accreditation of medical practices is widely used as a means to assure
      and improve medical care quality. Patient experience data contribute to a
      comprehensive quality assessment; some accreditation programmes therefore include
      patient surveys. Based on a commissioned work for Stiftung Praxissiegel, a
      provider of practice accreditation in Germany, nine international accreditation
      programmes were compared. Our study aimed at describing content, method and scope
      as well as differences, commonalities and unique features regarding the
      integration of patient experience data into international practice accreditation
      programmes. DESIGN: Selective literature review, subsequent systematic analysis
      of the identified documents. SETTING:  PARTICIPANTS: Nine accreditation
      programmes from Germany, Switzerland, UK, the Netherlands, USA and Australia.
      ANALYSIS:  MAIN OUTCOME MEASURES: Synthesis of key information on the
      accreditation programmes, the development of accreditation criteria, the
      different ways to assess patient experience data and the relevance of patient
      experience data to the accreditation decision. RESULTS: Structured patient
      surveys are mandatory in five accreditation programmes. Two programmes include
      the specific results of patient surveys in the accreditation decision. Three
      programmes require the results of patient surveys to be evaluated and, if
      necessary, to be used for quality improvement activities. CONCLUSIONS: Collecting
      patient experience data is of great importance for a comprehensive assessment of
      medical care quality. A practice accreditation programme that includes a
      structured patient survey can be considered as a high international standard. So
      far, there are insufficient research results on how and to what extent patient
      experience data is to be included in the accreditation decision.

PMID- 20144944
TI  - Inference of RhoGAP/GTPase regulation using single-cell morphological data from a
      combinatorial RNAi screen.
AB  - Biological networks are highly complex systems, consisting largely of enzymes
      that act as molecular switches to activate/inhibit downstream targets via post
      translational modification. Computational techniques have been developed to
      perform signaling network inference using some high-throughput data sources, such
      as those generated from transcriptional and proteomic studies, but comparable
      methods have not been developed to use high-content morphological data, which are
      emerging principally from large-scale RNAi screens, to these ends. Here, we
      describe a systematic computational framework based on a classification model for
      identifying genetic interactions using high-dimensional single-cell morphological
      data from genetic screens, apply it to RhoGAP/GTPase regulation in Drosophila,
      and evaluate its efficacy. Augmented by knowledge of the basic structure of
      RhoGAP/GTPase signaling, namely, that GAPs act directly upstream of GTPases, we
      apply our framework for identifying genetic interactions to predict signaling
      relationships between these proteins. We find that our method makes mediocre
      predictions using only RhoGAP single-knockdown morphological data, yet achieves
      vastly improved accuracy by including original data from a double-knockdown
      RhoGAP genetic screen, which likely reflects the redundant network structure of
      RhoGAP/GTPase signaling. We consider other possible methods for inference and
      show that our primary model outperforms the alternatives. This work demonstrates
      the fundamental fact that high-throughput morphological data can be used in a
      systematic, successful fashion to identify genetic interactions and, using
      additional elementary knowledge of network structure, to infer signaling
      relations.

PMID- 20144945
TI  - Does low self-esteem enhance social pain? The relationship between trait self
      esteem and anterior cingulate cortex activation induced by ostracism.
AB  - According to sociometer theory, self-esteem serves as a barometer of the extent
      to which individuals are socially included or excluded by others. We hypothesized
      that trait self-esteem would be related to social pain responsiveness, and we
      used functional magnetic resonance imaging to experimentally investigate this
      potential relationship. Participants (n = 26) performed a cyberball task, a
      computerized game of catch during which the participants were excluded from the
      game. Participants then rated the degree of social pain experienced during both
      inclusion in and exclusion from the game. Individuals with lower trait self
      esteem reported increased social pain relative to individuals with higher trait
      self-esteem, and such individuals also demonstrated a greater degree of dorsal
      anterior cingulate cortex activation. A psychophysiological interaction analysis
      revealed a positive connectivity between the dorsal anterior cingulate and
      prefrontal cortices for the lower trait self-esteem group, and a corresponding
      negative connectivity for the higher trait self-esteem group. Heightened dorsal
      anterior cortex activity and a corresponding connection with the prefrontal
      cortex might be one possible explanation for the greater levels of social pain
      observed experienced by individuals with low trait self-esteem.

PMID- 20144946
TI  - Regulatory impact factors: unraveling the transcriptional regulation of complex
      traits from expression data.
AB  - MOTIVATION: Although transcription factors (TF) play a central regulatory role,
      their detection from expression data is limited due to their low, and often
      sparse, expression. In order to fill this gap, we propose a regulatory impact
      factor (RIF) metric to identify critical TF from gene expression data. RESULTS:
      To substantiate the generality of RIF, we explore a set of experiments spanning a
      wide range of scenarios including breast cancer survival, fat, gonads and sex
      differentiation. We show that the strength of RIF lies in its ability to
      simultaneously integrate three sources of information into a single measure: (i)
      the change in correlation existing between the TF and the differentially
      expressed (DE) genes; (ii) the amount of differential expression of DE genes; and
      (iii) the abundance of DE genes. As a result, RIF analysis assigns an extreme
      score to those TF that are consistently most differentially co-expressed with the
      highly abundant and highly DE genes (RIF1), and to those TF with the most altered
      ability to predict the abundance of DE genes (RIF2). We show that RIF analysis
      alone recovers well-known experimentally validated TF for the processes studied.
      The TF identified confirm the importance of PPAR signaling in adipose development
      and the importance of transduction of estrogen signals in breast cancer survival
      and sexual differentiation. We argue that RIF has universal applicability, and
      advocate its use as a promising hypotheses generating tool for the systematic
      identification of novel TF not yet documented as critical.

PMID- 20144947
TI  - Microindel detection in short-read sequence data.
AB  - MOTIVATION: Several recent studies have demonstrated the effectiveness of
      resequencing and single nucleotide variant (SNV) detection by deep short-read
      sequencing platforms. While several reliable algorithms are available for
      automated SNV detection, the automated detection of microindels in deep short
      read data presents a new bioinformatics challenge. RESULTS: We systematically
      analyzed how the short-read mapping tools MAQ, Bowtie, Burrows-Wheeler alignment
      tool (BWA), Novoalign and RazerS perform on simulated datasets that contain
      indels and evaluated how indels affect error rates in SNV detection. We
      implemented a simple algorithm to compute the equivalent indel region eir, which
      can be used to process the alignments produced by the mapping tools in order to
      perform indel calling. Using simulated data that contains indels, we demonstrate
      that indel detection works well on short-read data: the detection rate for
      microindels (<4 bp) is >90%. Our study provides insights into systematic errors
      in SNV detection that is based on ungapped short sequence read alignments. Gapped
      alignments of short sequence reads can be used to reduce this error and to detect
      microindels in simulated short-read data. A comparison with microindels
      automatically identified on the ABI Sanger and Roche 454 platform indicates that
      microindel detection from short sequence reads identifies both overlapping and
      distinct indels. CONTACT: peter.krawitz@googlemail.com; peter.robinson@charite.de
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 20144948
TI  - Evolutionary conservation of residues in vertebrate DNA polymerase N conferring
      low fidelity and bypass activity.
AB  - POLN is a nuclear A-family DNA polymerase encoded in vertebrate genomes. POLN has
      unusual fidelity and DNA lesion bypass properties, including strong strand
      displacement activity, low fidelity favoring incorporation of T for template G
      and accurate translesion synthesis past a 5S-thymine glycol (5S-Tg). We searched
      for conserved features of the polymerase domain that distinguish it from
      prokaryotic pol I-type DNA polymerases. A Lys residue (679 in human POLN) of
      particular interest was identified in the conserved 'O-helix' of motif 4 in the
      fingers sub-domain. The corresponding residue is one of the most important for
      controlling fidelity of prokaryotic pol I and is a nonpolar Ala or Thr in those
      enzymes. Kinetic measurements show that K679A or K679T POLN mutant DNA
      polymerases have full activity on nondamaged templates, but poorly incorporate T
      opposite template G and do not bypass 5S-Tg efficiently. We also found that a
      conserved Tyr residue in the same motif not only affects sensitivity to
      dideoxynucleotides, but also greatly influences enzyme activity, fidelity and
      bypass. Protein sequence alignment reveals that POLN has three specific
      insertions in the DNA polymerase domain. The results demonstrate that residues
      have been strictly retained during evolution that confer unique bypass and
      fidelity properties on POLN.

PMID- 20144949
TI  - Rapid interactome profiling by massive sequencing.
AB  - We have developed a high-throughput protein expression and interaction analysis
      platform that combines cDNA phage display library selection and massive gene
      sequencing using the 454 platform. A phage display library of open reading frame
      (ORF) fragments was created from mRNA derived from different tissues. This was
      used to study the interaction network of the enzyme transglutaminase 2 (TG2), a
      multifunctional enzyme involved in the regulation of cell growth, differentiation
      and apoptosis, associated with many different pathologies. After two rounds of
      panning with TG2 we assayed the frequency of ORFs within the selected phage
      population using 454 sequencing. Ranking and analysis of more than 120,000
      sequences allowed us to identify several potential interactors, which were
      subsequently confirmed in functional assays. Within the identified clones, three
      had been previously described as interacting proteins (fibronectin, SMOC1 and
      GSTO2), while all the others were new. When compared with standard systems, such
      as microtiter enzyme-linked immunosorbant assay, the method described here is
      dramatically faster and yields far more information about the interaction under
      study, allowing better characterization of complex systems. For example, in the
      case of fibronectin, it was possible to identify the specific domains involved in
      the interaction.

PMID- 20144950
TI  - Strong dependence between functional domains in a dual-function snoRNA infers
      coupling of rRNA processing and modification events.
AB  - Most small nucleolar RNAs (snoRNAs) guide rRNA nucleotide modifications, some
      participate in pre-rRNA cleavages, and a few have both functions. These
      activities involve direct base-pairing of the snoRNA with pre-rRNA using
      different domains. It is not known if the modification and processing functions
      occur independently or in a coordinated manner. We address this question by
      mutational analysis of a yeast box H/ACA snoRNA that mediates both processing and
      modification. This snoRNA (snR10) contains canonical 5'- and 3'-hairpin
      structures with a guide domain for pseudouridylation in the 3' hairpin. Our
      functional mapping results show that: (i) processing requires the 5' hairpin
      exclusively, in particular a 7-nt element; (ii) loss of the 3' hairpin or
      pseudouridine does not affect rRNA processing; (iii) a single nucleotide
      insertion in the guide domain shifts modification to an adjacent uridine in rRNA,
      and severely impairs both processing and cell growth; and (iv) the deleterious
      effects of the insertion mutation depend on the presence of the processing
      element in the 5' hairpin, but not modification of the novel site. Together, the
      results suggest that the snoRNA hairpins function in a coordinated manner and
      that their interactions with pre-rRNA could be coupled.

PMID- 20144951
TI  - Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS
      induced transactivation of miRNA genes in human biliary epithelial cells.
AB  - The majority of human miRNA genes is transcribed by polymerase II and can be
      classified as class II genes similar to protein-coding genes. Whereas current
      research on miRNAs has focused on the physiological and pathological functions,
      the molecular mechanisms underlying their transcriptional regulation are largely
      unknown. We recently reported that lipopolysaccharide (LPS) alters mature miRNA
      expression profile in human biliary epithelial cells. In this study, we tested
      the role of transcription factor NF-kappaB in LPS-induced transcription of select
      miRNA genes. Of the majority of LPS-up-regulated mature miRNAs in cultured human
      biliary epithelial cells, potential NF-kappaB binding sites were identified in
      the putative promoter elements of their corresponding genes. Inhibition of NF
      kappaB activation by SC-514, an IKK2 inhibitor, blocked LPS-induced up-regulation
      of a subset of pri-miRNAs, including pri-miR-17-92, pri-miR-125b-1, pri-miR-21,
      pri-miR-23b-27b-24-1, pri-miR-30b, pri-miR-130a and pri-miR-29a. Moreover, direct
      binding of NF-kappaB p65 subunit to the promoter elements of mir-17-92, mir-125b
      1, mir-21, mir-23b-27b-24-1, mir-30b and mir-130a genes was identified by
      chromatin immunoprecipitation analysis and confirmed by the luciferase reporter
      assay. Thus, a subset of miRNA genes is regulated in human biliary epithelial
      cells through NF-kappaB activation induced by LPS, suggesting a role of the NF
      kappaB pathway in the transcriptional regulation of miRNA genes.

PMID- 20144952
TI  - Structural determinants of specific DNA-recognition by the THAP zinc finger.
AB  - Human THAP1 is the prototype of a large family of cellular factors sharing an
      original THAP zinc-finger motif responsible for DNA binding. Human THAP1
      regulates endothelial cell proliferation and G1/S cell-cycle progression, through
      modulation of pRb/E2F cell-cycle target genes including rrm1. Recently, mutations
      in THAP1 have been found to cause DYT6 primary torsion dystonia, a human
      neurological disease. We report here the first 3D structure of the complex formed
      by the DNA-binding domain of THAP1 and its specific DNA target (THABS) found
      within the rrm1 target gene. The THAP zinc finger uses its double-stranded beta
      sheet to fill the DNA major groove and provides a unique combination of contacts
      from the beta-sheet, the N-terminal tail and surrounding loops toward the five
      invariant base pairs of the THABS sequence. Our studies reveal unprecedented
      insights into the specific DNA recognition mechanisms within this large family of
      proteins controlling cell proliferation, cell cycle and pluripotency.

PMID- 20144953
TI  - Targeting of the cytosolic poly(A) binding protein PABPC1 to mitochondria causes
      mitochondrial translation inhibition.
AB  - Mammalian mitochondria contain their own genome that is almost fully transcribed
      from both strands, generating polycistronic RNA units that are processed and
      matured. The mitochondrial mRNA is modified by oligo- or polyadenylation at the
      3' termini, but the exact function of this post-transcriptional addition is
      unclear. Current debate focuses on the role of polyadenylation in transcript
      stability. An equally likely function that has received little attention is that,
      as in the cytosol of eukaryotes, polyadenylation facilitates translation in the
      mitochondrion. To address this issue, we have targeted cytosolic proteins to the
      mitochondrion, a poly(A) specific 3' exoribonuclease, mtPARN, and a
      poly(A)binding protein, mtPABP1. Removal of the 3' adenylyl extensions had a
      variable effect on mt-mRNA steady-state levels, increasing (MTND1, 2, 5) or
      decreasing (MTCO1, 2, RNA14) certain species with minimal effect on others (RNA7,
      MTND3). Translation was markedly affected, but interpretation of this was
      complicated by the concomitant 3' truncation of the open reading frame in most
      cases. Coating of the poly(A) tail by mtPABP1, however, did not lead to
      transcript decay but caused a marked inhibition of mitochondrial translation.
      These data are consistent with endogenous RNA-binding factor(s) interacting with
      the poly(A) to optimize mitochondrial protein synthesis.

PMID- 20144954
TI  - On the benefit of Teucrium in murine colitis through improvement of toxic
      inflammatory mediators.
AB  - Regarding the role of free radicals in pathogenesis of inflammatory bowel disease
      (IBD), we were interested to investigate the effects of Teucrium persicum with
      approved antioxidant and anti-inflammatory properties in an experimental model of
      colitis. Immunologic colitis was induced by rectal administration of a mixture of
      2,4,6-trinitrobenzene sulphonic acid (TNBS) and ethanol through rubber cannula
      into rats. Three different doses of Teucrium (100, 200, and 400 mg/kg) were
      gavaged in a duration of 10 days to rats. Endpoint markers of colitis included
      macroscopic and microscopic examination of colon tissue and measuring colonic
      cells concentrations of tumor necrosis factor-alpha (TNF-alpha), interlukin-1beta
      (IL-1beta), total antioxidant power as ferric reducing antioxidant power (FRAP),
      myeloperoxidase (MPO), and lipid peroxidation as thiobarbitoric acid-reactive
      substance (TBARS). Teucrium at all doses improved both macroscopic and
      histological damages of rats with colitis. Teucrium reduced colonic MPO activity
      and concentrations of cellular lipid peroxides, TNF-alpha, and IL-1beta, with a
      concomitant increase in FRAP value in rats with colitis. It is concluded that
      beneficial effects of Teucrium in experimental colitis is mediated through its
      antioxidant and anti-inflammatory potentials. Examination of this herbal medicine
      in patients with IBD as a supplement would further reveal the potential of
      Teucrium.

PMID- 20144955
TI  - Protective role of tannin-rich fraction of Camellia sinensis in tissue arsenic
      burden in Sprague Dawley rats.
AB  - The protective effect of green tea (Camellia sinensis) was tested against arsenic
      induced toxicity. However, the possible role of tannins in green tea in
      alleviating hepatic and renal oxidative injury has also been studied.
      Administration of sodium arsenite (100 mg/kg/day) for 28 days in Sprague Dawley
      female rats resulted in significant reduction of biochemical parameters such as
      delta-aminolevulinic acid dehydratase (ALAD), reduced glutathione (GSH),
      glutathione peroxidase (GPx), superoxide dismutase (SOD) and elevation of
      thiobarbituric acid reactive substances (TBARS) and the index of nitrite/nitrate
      (NOx) levels. The tissue arsenic burden was increased after arsenic exposure for
      a period of 28 days. Green tea crude fraction (GTC) co-treated with sodium
      arsenite for 28 days caused significant (p < .01) elevation of ALAD, GSH, GPx,
      SOD, and nitrate/nitrite levels and reduction of the TBARS level and tissue
      burden when compared to detannified green tea fraction (GTDT)-treated groups. The
      protective role of tannin-rich fraction of C. sinensis when compared to the
      detannified fraction was also confirmed by histological examinations. The greater
      activity of GTC than that of detannified green tea fraction correlates with the
      higher content of tannins in green tea. Overall, these results indicate that the
      tannin-rich green tea could have improved the defense mechanism against arsenic
      induced oxidative stress and reduced the tissue arsenic burden.

PMID- 20144956
TI  - A crucial role of nitric oxide in acute lung injury secondary to the acute
      necrotizing pancreatitis.
AB  - To investigate the role of nitric oxide (NO) in acute lung inflammation and
      injury secondary to acute necrotizing pancreatitis (ANP), 5% sodium taurocholate
      was retrogradely injected into the biliopancreatic duct of rats to ANP model.
      These ANP rats were given L-Arginine (L-Arg, 100 mg/kg), L-NAME (10 mg/kg), or
      their combination by intraperitoneal injection 30 min prior to ANP induction. At
      1, 3, 6, and 12 hours after ANP induction, lung NO production, and inducible NO
      synthase (iNOS) expression were measured. Lung histopathological changes,
      bronchoalveolar lavage (BAL) protein concentration, proinflammatory mediators
      tumor necrotic factor alpha (TNF-alpha), and lung tissue myeloperoxidase (MPO)
      activity were examined. Results showed that NO production and iNOS mRNA
      expression in alveolar macrophages (AMs) were significantly increased along with
      significant increases in lung histological abnormalities and BAL proteins in the
      ANP group, all of which were further enhanced by pretreatment with L-Arg and
      attenuated by pretreatment with L-NAME, respectively. These markers were slightly
      attenuated by pretreatment with combination of L-Arg + L-NAME, suggesting that NO
      is required for initiating the acute lung damage in ANP rats, and also that L-Arg
      enhanced lung injury is mediated by its NO generation rather than its direct
      effect. MPO activity and TNF-alpha expression in lung were upregulated in the ANP
      rats and further enhanced by pretreatment with L-Arg and attenuated by
      pretreatment with L-NAME, respectively. These results suggest that overproduction
      of NO mediated by iNOS in the lung is required for the acute lung inflammation
      and damage secondary to ANP.

PMID- 20144957
TI  - Effect of di(2-ethylhexyl) phthalate (DEHP) on lipolysis and lipoprotein lipase
      activities in adipose tissue of rats.
AB  - The di(2-ethylhexyl) phthalate (DEHP) is an ubiquitous environmental chemical
      with detrimental health effects. The present work was designed to asses some
      potential mechanisms by which DEHP causes, among others, a reduced body fat
      retention. Since this effect could be related to an alteration of adipocyte
      triacylglycerol (TG) metabolism, we evaluated the effects of dietary DEHP in
      adipose tissues upon (1) the number and size of fat cells; (2) the basal and
      stimulated lipolysis and (3) the lipoprotein lipase (LPL) activity. Groups of
      male Wistar rats were fed for 21 days a control diet alone (control group) or the
      same control diet supplemented with 2% (w/w) of DEHP (DEHP group). The LPL
      activity of DEHP-fed rats was increased in lumbar and epididymal adipose tissues.
      These rats had significantly reduced weight in epididymal and lumbar tissues,
      together with reduced size of epididymal adipocytes. These alterations do not
      seem to be associated with higher lipid mobility because neither basal lipolysis
      nor 'in vitro' stimulated lipolysis by noradrenaline (NA) showed to be modified
      by DEHP. Based on these results, we concluded that the adipose tissue size
      reduction induced by DEHP intake is not due to changes in lipolysis nor to a
      decreased LPL activity. More research is needed to achieve a comprehensive
      understanding of the potential mechanisms by which DEHP causes, among others, a
      reduced body fat retention.

PMID- 20144958
TI  - Chromosomal aberrations induced by imipramine and desipramine in mouse.
AB  - Imipramine (IMI) and desipramine (DES) are two drugs widely used for the
      treatment of depression as well as for other diseases. In the present study, we
      determined their capacity to induce chromosomal aberrations in mouse bone marrow
      cells. Three doses of each compound were tested and their results were compared
      with the frequency of chromosomal aberrations obtained in a control group as well
      as with a group treated with cyclophosphamide. Our results showed a significant
      increase in chromosome damage with the doses tested for each compound: 7, 20, and
      60 mg/kg in the case of IMI, and 2, 20, and 60 mg/kg as regards DES. This last
      drug induced stronger chromosomal damage than IMI. Our results agree with
      previous studies regarding the induction of micronuclei and sister chromatid
      exchanges by the drugs in mouse and suggest caution with respect to their use in
      long-term treatments.

PMID- 20144959
TI  - Pyrrolizidine alkaloid clivorine induced oxidative injury on primary cultured rat
      hepatocytes.
AB  - Clivorine is an otonecine-type hepatotoxic pyrrolizidine alkaloid (HPAs), to
      which humans are exposed when consuming herbs containing such components. In the
      present study, we investigated clivorine-induced oxidative stress injury on
      primary cultured rat hepatocytes. Rat hepatocytes were treated with various
      concentrations of clivorine (1-100 microM) for 48 hours, and then cell viability
      was detected by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide
      (MTT) assay, while lipid peroxidation (LPO) level, glutathione peroxidase (GPx),
      glutathione-S-transferase (GST), glutathione reductase (GR), catalase (CAT) and
      superoxide dismutase (SOD) activities were determined to evaluate the oxidative
      injury. The results of MTT assay showed that clivorine decreased cell viability
      in a concentration-dependent manner. Clivorine also increased LPO amounts in rat
      hepatocytes at the concentrations of 50 microM and 100 microM. Further results
      showed that clivorine decreased GPx, GST and GR activities, which are all reduced
      glutathione (GSH)-related antioxidant enzymes. CAT and SOD are both important
      antioxidant enzymes, and the results showed that clivorine increased CAT activity
      at the low concentration of 5 muM and decreased cellular SOD activity at all
      concentrations. Taken together, our results demonstrated that clivorine induced
      toxicity on primary cultured rat hepatocytes by causing the damage on cellular
      redox balance.

PMID- 20144960
TI  - Pattern of acute food, drug, and chemical poisoning in Sari City, Northern Iran.
AB  - This descriptive and retrospective study was conducted at the poisoning ward of
      Imam teaching hospital, Sari, Iran, with the aim of evaluating the pattern of
      poisoning. Hence, the medical profiles of 2057 patients, who were admitted, were
      carefully reviewed during the period from April 2006 to March 2008 for 2 years.
      During this period, 2057 cases, 53.9% female and 46.1% male, were admitted with
      the indication of acute poisoning. The greatest proportion of poisoning occurred
      between the ages of 18 and 29 years, with suicidal intentions. Most cases of
      poisoning were intentional (85%). The most common agents involved in acute
      poisoning were drugs (77.7%), especially sedatives/hypnotics such as
      benzodiazepines, followed by opioid analgesics. Organophosphate and carbamate
      insecticides were the third major agent that induced poisoning. Twenty-seven
      patients (1.3%) who were mostly females and young adults died. Death mostly
      occurred due to organophosphate and carbamate insecticides (19 cases) poisoning,
      followed by sedatives/hypnotics like benzodiazepines (3 cases). High prevalence
      of intentional overdose and mortality among young adults requires considerable
      attention and further studies to find out the underlying causes. In addition,
      strict rules must be followed regarding the sale of central nervous system drugs
      and pesticides, particularly organophosphate and carbamate insecticides.
      Establishing poison information centers in different parts of the country,
      preparing national treatment guidelines, training healthcare providers, and
      ensuring easy availability of the antidotes are also recommended.

PMID- 20144961
TI  - Over 8 years experience on severe acute poisoning requiring intensive care in
      Hong Kong, China.
AB  - In order to obtain up-to-date information on the pattern of severe acute
      poisoning and the characteristics and outcomes of these patients, 265 consecutive
      patients admitted to an intensive care unit in Hong Kong for acute poisoning from
      January 2000 to May 2008 were studied retrospectively. Benzodiazepine (25.3%),
      alcohol (23%), tricyclic antidepressant (17.4%), and carbon monoxide (15.1%) were
      the four commonest poisons encountered. Impaired consciousness was common and
      intubation was required in 67.9% of admissions, with a median duration of
      mechanical ventilation of less than 1 day. The overall mortality was 3.0%. Among
      the 257 survivors, the median lengths of stay in the intensive care unit and
      acute hospital (excluding days spent in psychiatric ward and convalescent
      hospital) were less than 1 day and 3 days, respectively. Factors associated with
      a longer length of stay included age of 65 or older, presence of comorbidity,
      Acute Physiology and Chronic Health Evaluation II score of 25 or greater, and
      development of shock, rhabdomyolysis, and aspiration pneumonia, while alcohol
      intoxication was associated with a shorter stay. This is the largest study of its
      kind in the Chinese population and provided information on the pattern of severe
      acute poisoning requiring intensive care admission and the outcomes of the
      patients concerned.

PMID- 20144962
TI  - High prevalence of hypokalemia after acute acetaminophen overdose: impact of
      psychiatric illness.
AB  - BACKGROUND: Hypokalemia is not an isolated disease but an associated finding in a
      number of different diseases. It is also a commonly neglected condition among
      patients with acute acetaminophen overdose. OBJECTIVES: This study intended to
      determine the prevalence of hypokalemia and its clinical correlates in acute
      psychiatric illness among hypokalemic and normokalemic patients after
      acetaminophen overdose. METHODS: This is a retrospective cohort study of hospital
      admissions for acute acetaminophen overdose conducted over a period of 5 years
      from 1 January 2004 to 31 December 2008. Demographic data and different types of
      psychiatric illness were compared between hypokalemic and normokalemic patients.
      Hypokalemia was predefined by a serum concentration <3.5 mmol/L. Statistical
      Package for Social Sciences (SPSS) 15 was used for data analysis. RESULTS: Two
      hundred and eighty patients out of 305 admissions were studied. Hypokalemia was
      found in 63.6% of patients with a higher prevalence in the presence of
      psychiatric illness (67.7%). Hypokalemic patients were significantly associated
      with the presence of major depression (p = .04), adjustment disorder (p < .001),
      anxiety (p = .01), and suicidal attempts (p = .04). CONCLUSION: Hypokalemia was
      common among patients with psychiatric illness and acute acetaminophen overdose.

PMID- 20144963
TI  - Wild mushroom poisonings in the Middle Black Sea region in Turkey: analyses of 6
      years.
AB  - Wild mushroom poisoning (MP) is an important medical emergency that may have
      serious clinical outcome. The aim of this study was to evaluate the demographic
      and clinical features of patients with wild MP. This study was designed
      retrospectively by examining files of the patients with wild MP who were admitted
      to Ondokuz Mayis University Emergency Department, between January 2002 and
      December 2007. Patients > or =16 years of age were included in the study. A total
      of 317 patients poisoned by wild mushrooms (mean age, 42.0 +/- 16.3 years; 67.5%
      female) were studied. All poisonings were accidental, i.e. consumption of wild
      mushrooms collected from open fields and woodlands or purchased from local
      bazaars. The common symptoms and complaints on admission were nausea (86.8%) and
      vomiting (79.8%). The poisoning latent phase in most cases was <6 hours (86.8%).
      Most of the poisonings occurred in autumn (59.6%). Three patients died in the
      hospital due to acute liver failure and complications. The duration of
      hospitalization was a median 3 days (range: 1-12 days). The public should be
      informed about the probable hazards of wild mushroom ingestion.

PMID- 20144964
TI  - Aqueous extract of Securidaca longepedunculata root induce redox imbalance in
      male rat liver and kidney.
AB  - The effect of aqueous extract of Securidaca longepedunculata root on redox
      homeostasis in male rat liver and kidney was investigated. Rats were grouped into
      four: A, B, C and D, where A (the control) received orally 1 mL of distilled
      water; B, C and D (test groups) received orally 200, 400 and 800 mg/kg body
      weight of the extract, respectively, for 28 days. Extract administration
      significantly reduced (p < .05) alkaline phosphatase activity in the liver and
      kidney with corresponding increases in the serum. Acid phosphatase activity
      increased significantly (p < .05) in the liver and kidney, while there was no
      significant change (p > .05) in the serum acid phosphatase activity. There was
      also significant decrease (p < .05) in the activities of superoxide dismutase,
      catalase, glutathione peroxidase and glutathione reductase in the liver and
      kidney. Liver and kidney levels of GSH, vitamins C and E were also significantly
      reduced (p < .05). Serum malonidialdehyde and lipid hydroperoxide increased
      significantly (p < .05) in all the extract-treated groups. The available data
      from this study revealed that aqueous extract of S. longepedunculata root exerted
      its toxicity in the animals by depleting the antioxidant systems. This may
      consequently expose the cells and cellular macromolecules to oxidative damage by
      reactive oxygen species generated either from the metabolism of the extract or
      other in vivo means.

PMID- 20144967
TI  - Sterilisation and the birth of a right: effective access to medical records.

PMID- 20144966
TI  - African ancestry allelic variation at the MYH9 gene contributes to increased
      susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans.
AB  - Recent studies identified MYH9 as a major susceptibility gene for common forms of
      non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA
      sequence variants comprising the E-1 haplotype, was significantly associated with
      ESKD. In order to determine whether African ancestry variants are also associated
      with disease susceptibility in admixed populations with differing genomic
      backgrounds, we genotyped a total of 1425 African and Hispanic American subjects
      comprising dialysis patients with diabetic and non-diabetic ESKD and controls,
      using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40
      genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry
      correction, logistic regression demonstrated that three of the E-1 SNPs are also
      associated with non-diabetic ESKD in the new sample sets of both African and
      Hispanic Americans, with a stronger association in Hispanic Americans. We also
      identified MYH9 SNPs that are even more powerfully associated with the disease
      phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into
      those comprising a haplotype termed S-1 whose association was significant under a
      recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic
      Americans, recessive), and those comprising a haplotype termed F-1 whose
      association was significant under a dominant or additive inheritance mode
      (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings
      strengthen the contention that a sequence variant of MYH9, common in populations
      with varying degrees of African ancestry admixture, and in strong linkage
      disequilibrium with the associated SNPs and haplotypes reported herein, strongly
      predisposes to non-diabetic ESKD.

PMID- 20144965
TI  - Ocular side effects of anti-rheumatic medications: what a rheumatologist should
      know.
AB  - Nearly every drug may cause changes to ocular tissues through a variety of
      mechanisms. Medication overdoses, drug-drug interactions but also chronic
      administration of medications at the recommended doses may lead to ocular
      toxicity. The ocular side effects, screening for eye toxicity and treatment
      guidelines for anti-inflammatory and immunosuppressive drugs commonly used by
      rheumatologists are reviewed herein.

PMID- 20144968
TI  - Pilot quality assurance programme for plasma metanephrines.
AB  - BACKGROUND: Up to 2007 there was no formal external quality assurance programme
      for plasma free metanephrines. A pilot programme was conceived by the AACB
      (Australian Association of Clinical Biochemists) Working Party on biogenic
      amines. With support from the AACB and Royal College of Pathologists of
      Australasia Quality Assurance programmes, a pilot study was developed. Data from
      this study are presented for the first time. METHODS: Twelve lyophilized plasma
      samples were distributed to 15 centres. Samples were spiked with metanephrine
      (metadrenaline), normetanephrine (normetadrenaline) and 3-methoxytyramine, all
      derived from human urine. Concentrations were arranged in a linear relationship.
      The analytes were present at six levels and samples were duplicated. RESULTS:
      High-pressure liquid chromatography and tandem mass spectrometry methods showed
      acceptable precision but in general enzyme immunoassay displayed a higher degree
      of imprecision as well as a negative bias. CONCLUSIONS: Differences in
      calibration and matrix effects are likely to have been responsible for the
      discrepancy between chromatographic and immunoassay methods. These differences
      need to be further examined although efforts at standardization between different
      methods have been hampered by the lack of a universal calibrator for plasma
      metanephrines. Meanwhile, a laboratory's performance characteristics can be
      monitored and enhanced by participation in suitable external quality assurance
      programmes.

PMID- 20144969
TI  - Ischaemia-modified albumin: fact or fiction?

PMID- 20144970
TI  - Shortness of breath: flushing out the diagnosis.
AB  - We report a 63-year-old man who presented with breathlessness and weight loss and
      was diagnosed on echocardiography to have carcinoid heart disease. It was later
      transpired that he underwent surgical removal of an ileal carcinoid tumour 19
      years previously.

PMID- 20144971
TI  - Biochemical risk factors for stone formation in a Scottish paediatric hospital
      population.
AB  - BACKGROUND: Renal stones in children, although rare, may be associated with
      morbidity and renal damage. Scottish children have a different ethnic composition
      and diet compared with paediatric populations previously studied. Urinary stone
      promoters include calcium, oxalate and urate. Postulated inhibitors include
      citrate and glycosaminoglycans (GAGs). We tested the hypothesis that Scottish
      paediatric stone-formers have higher excretion of urinary stone promoters
      (calcium/oxalate/urate) and/or lower excretion of stone inhibitors (citrate/GAGs)
      than children with isolated haematuria and controls. METHODS: In this case
      controlled study, we measured creatinine, calcium, oxalate, urate, citrate and
      GAGs in random urine samples from 24 stone-formers (excluding inherited metabolic
      disorders), median age 10.2 (range 1.0-17.2) y; 25 patients with isolated
      haematuria, 6.3 (0.6-13.7) y; and 32 controls, 7.5 (0.8-14.7) y. RESULTS:
      Excretion of urinary promoters and inhibitors differed among stone-formers,
      haematuria and control groups for (median (range)): calcium (0.82 (0.02-2.19),
      0.43 (0.08-2.65), 0.31 (0.04-2.12) mmol/mmol creatinine, respectively, P =
      0.005), citrate (0.42 (0.13-0.72), 0.33 (0.05-0.84), 0.61 (0.11-1.75) mmol/mmol
      creatinine, P = 0.001), calcium:citrate ratio (1.68 (0.19-4.81), 1.30 (0.19
      9.57), 0.54 (0.10-2.27) mmol/mmol, P < 0.0001) and the promoter:inhibitor ratio
      (calcium x oxalate)/(citrate x GAGs) (8.3 (1.0-82.5), 4.3 (1.2-69.5), 2.8 (0.3
      13.2) mmol/g, P < 0.0001). CONCLUSIONS: Scottish paediatric stone-formers had
      lower urinary citrate excretion and higher urinary calcium excretion,
      calcium:citrate ratio and promoter:inhibitor ratio compared with controls.
      Urinary calcium excretion and promoter:inhibitor ratio was also higher than
      children with isolated haematuria. Nevertheless, marked overlap between the stone
      former and haematuria groups for promoter:inhibitor and calcium:citrate ratios
      suggests that some patients with isolated haematuria may be at future risk of
      urolithiasis.

PMID- 20144972
TI  - Response to an audit of oral glucose tolerance testing.

PMID- 20144973
TI  - Spurious hypokalaemia and hypophosphataemia due to extreme hyperleukocytosis in a
      patient with a haematological malignancy.
AB  - Serious hyperleukocytosis can strongly affect laboratory results of potassium,
      phosphate and arterial oxygen tension. A 40-year-old woman is presented with an
      acute myeloid leukaemia and a strongly elevated leukocyte count (310 x 10(9)/L).
      Apart from this hyperleukocytosis, initial blood tests showed hypokalaemia,
      hypophosphataemia and serious hypoxaemia without any corresponding complaints.
      Blood sampled and transported on ice or directly analysed showed no electrolyte
      abnormalities and hypoxaemia. The observed discrepancy in laboratory results is
      probably due to the metabolic activity of the leukocytes in vitro. Spurious
      laboratory results can be a reason for incorrect decisions concerning additional
      diagnostics and treatment. In conclusion, hyperleukocytosis can cause
      pseudohypokalaemia, pseudohypophosphataemia and pseudohypoxaemia, which can be
      prevented by correct sampling and immediate analysis.

PMID- 20144974
TI  - Acidification and urinary calcium.

PMID- 20144975
TI  - Automated assay for determining cellular cholesterol using a random access
      chemistry analyser.
AB  - BACKGROUND: We have previously reported an ultrasensitive fluorometric assay for
      measuring cellular cholesterol. Although this technique is reliable, the use of
      the assay has limitations due to the requirement for special equipment. It is
      therefore difficult to apply this assay for the routine determination of cellular
      cholesterol. METHODS: A colorimetric assay to measure cellular cholesterol was
      established that utilizes reagents widely used for the measurement of cholesterol
      in blood samples in conjunction with a random access chemistry analyser ARCHITECT
      c8000 that is also common in clinical laboratories. RESULTS: This colorimetric
      assay showed excellent linearity and recovery. The within-run coefficients of
      variation were less than 2.5%. The sensitivity of this method, with its detection
      limit of 1.29 mumol/L, was found to be superior to that of the fluorometric assay
      we have developed previously. In platelets obtained from patients with diabetes,
      both the free cholesterol and cholesterol ester content were significantly
      increased. CONCLUSIONS: Using this technique, measurement of cellular cholesterol
      could be performed routinely without the requirement for special reagents and
      equipment.

PMID- 20144976
TI  - Investigation of the potential association of vitamin D binding protein with
      lipoproteins.
AB  - BACKGROUND: Vitamin D binding protein (DBP) acts as a vitamin D carrier and an
      actin scavenger. We have previously reported a correlation between serum DBP and
      lipid parameters in a cystic fibrosis population. In the present study, the
      relationship between serum DBP, lipoprotein fractions and vitamin D is
      investigated. METHODS: The presence of DBP in lipoprotein fractions was examined
      using precipitation, gel permeation chromatography and ultracentrifugation. The
      association between DBP and lipids was investigated in a cohort study of 211 men.
      Total and actin-free DBP concentrations were assessed by immunonephelometry and
      enzyme-linked immunosorbent assay. Serum 25(OH)- and 1.25(OH)(2)-vitamin D(3)
      were assayed by radioimmunoassay. Total cholesterol, high-density lipoprotein
      cholesterol (HDL), triglycerides and insulin were measured using routine methods.
      Low-density lipoprotein-cholesterol (LDL) was calculated according to
      Friedewald's formula. RESULTS: DBP was found to be present in very-low-density
      lipoprotein (VLDL). Gel permeation chromatography revealed a bimodal DBP
      distribution with a lipid-bound fraction besides the known free fraction.
      Ultracentrifugation confirmed the presence of DBP and 25(OH)-vitamin D(3) in the
      VLDL particle. Total serum DBP concentration and the actin-bound DBP/DBP ratio
      correlated significantly with total cholesterol, LDL-cholesterol, triglycerides
      and albumin. The 25(OH)-vitamin D(3)/DBP ratio correlated negatively with serum
      triglyceride concentration and body mass index (BMI). The actin-bound DBP complex
      was identified with Western blot. CONCLUSIONS: The lipid-bound DBP fraction may
      be of greater importance than initially thought. The present findings may have
      clinical consequences in view of the important physiological role of DBP.

PMID- 20144977
TI  - Effect of transport temperature on the Scantibodies total intact parathyroid
      hormone immunoradiometric assay using the RIAMAT-280.
AB  - BACKGROUND: Inadequate temperature affects the stability of intact parathyroid
      hormone (i-PTH) kits. Room temperature during transport modifies i-PTH results.
      METHOD: Percent bound (%B/Bmax) and concentrations (pmol/L) of standards,
      controls (C1, C2) and pool from eight standard curves were divided into: group I
      (three curves from kits kept at room temperature for more than 48 h) and group II
      (five curves from kits kept at 2-8 degrees C) during transport. i-PTH was
      measured using Scantibodies total i-PTH assay with RIAMAT-280. RESULTS: %B/Bmax
      for standards, C1 and C2 were significantly higher in group I versus II (P =
      0.04). %B/Bmax for the pool were significantly lower in group I (P = 0.001). i
      PTH pool concentration in group I was 51% lower (95% confidence interval, 47-53%,
      P = 0.001); differences were not significant for C1 (P = 0.25) and C2 (P = 0.57)
      in both groups. CONCLUSION: Room temperature on i-PTH kit during transport alters
      the standard curve, resulting in a decrease in i-PTH. Using a pool as internal
      quality control allows the detection of these changes not detected by kit
      controls.

PMID- 20144978
TI  - Imprecision of tumour biomarker measurements on Roche Modular E170 platform
      fulfills desirable goals derived from biological variation.
AB  - BACKGROUND: Monitoring of test imprecision is one of the most important quality
      indicators in clinical laboratories. Imprecision goals should be derived from
      biological variation. The aim of this study was to evaluate the imprecision of
      eight tumour biomarker assays routinely measured on the Modular E170 system.
      METHODS: Method coefficient of variations (CVs) were obtained by an appropriate
      Internal Quality Control programme based on the measurement every working day of
      a fresh-frozen human serum pool with biomarkers concentrations around the
      clinical cut-offs. We evaluated data collected along the whole year 2008 (n
      range: 21-461); monthly CVs and their cumulative means were calculated and
      compared with corresponding goals. RESULTS: Biomarkers concentration means and
      average yearly CVs (desirable goals in parentheses) were as follows: alpha
      fetoprotein, 9.6 microg/L, 3.9% (6.0%); CA125, 41.2 U/L, 2.8% (12.4%); CA15.3,
      32.7 U/L, 3.1% (3.1%); CA19.9, 35.1 U/L, 2.8% (8.0%); CEA, 7.7 microg/L, 4.3%
      (6.4%); prostate-specific antigen (PSA), 4.1 microg/L, 4.3% (9.1%); CYFRA 21.1,
      2.4 microg/L, 5.7% (11.3%); and ferritin, 64.5 microg/L, 4.0% (7.1%).
      CONCLUSIONS: Our study shows that in routine laboratory practice and over a
      clinically and analytically relevant time-span, the imprecision of the tumour
      biomarker measurements on the Roche Modular E170 fulfills desirable goals. For
      four assays (CA125, CA19.9, PSA and CYFRA 21.1) the optimum CV can even be
      achieved.

PMID- 20144979
TI  - Developmental programming of adult adrenal structure and steroidogenesis: effects
      of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids.
AB  - Fetal glucocorticoid excess programs a range of detrimental outcomes in the adult
      phenotype, at least some of which may be due to altered adult adrenocortical
      function. In this study, we determined the effects of maternal dexamethasone
      treatment on offspring adrenal morphology and function, as well as the
      interactive effects of postnatal dietary omega-3 (n-3) fatty acids. This
      postnatal dietary intervention has been shown to alleviate many of the
      programming outcomes in this model, but whether this is via the effects on
      adrenal function is unknown. Dexamethasone acetate was administered to pregnant
      rats (0.75 microg/ml drinking water) from day 13 to term. Cross-fostered
      offspring were raised on either a standard or high-n-3 diet. Adrenal weight
      (relative to body weight) at 6 months of age was unaffected by prenatal
      dexamethasone, regardless of postnatal diet, and stereological analysis showed no
      effect of dexamethasone on the volumes of adrenal components (zona glomerulosa,
      zona fasciculata/reticularis or adrenal medulla). Expression of key steroidogenic
      genes (Cyp11a1 and Star) was unaffected by either prenatal dexamethasone or
      postnatal diet. In contrast, adrenal expression of Mc2r mRNA, which encodes the
      ACTH receptor, was higher in offspring of dexamethasone-treated mothers, an
      effect partially attenuated by the Hn3 diet. Moreover, stress-induced levels of
      plasma and urinary corticosterone and urinary aldosterone were elevated in
      offspring of dexamethasone-treated mothers, indicative of enhanced adrenal
      responsiveness. In conclusion, this study shows that prenatal exposure to
      dexamethasone does not increase basal adrenocortical activity but does result in
      a more stress-responsive adrenal phenotype, possibly via increased Mc2r
      expression.

PMID- 20144980
TI  - Hormonal regulation of male germ cell development.
AB  - Over the past five decades, intense research using various animal models,
      innovative technologies notably genetically modified mice and wider use of
      stereological methods, unique agents to modulate hormones, genomic and proteomic
      techniques, have identified the cellular sites of spermatogenesis, that are
      regulated by FSH and testosterone. It has been established that testosterone is
      essential for spermatogenesis, and also FSH plays a valuable role. Therefore
      understanding the basic mechanisms by which hormones govern germ cell progression
      are important steps towards improved understating of fertility regulation in
      health diseases.

PMID- 20144981
TI  - Neurological outcomes at 18 months of age after moderate hypothermia for
      perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial
      data.
AB  - OBJECTIVE: To determine whether moderate hypothermia after hypoxic-ischaemic
      encephalopathy in neonates improves survival and neurological outcome at 18
      months of age. DESIGN: A meta-analysis was performed using a fixed effect model.
      Risk ratios, risk difference, and number needed to treat, plus 95% confidence
      intervals, were measured. DATA SOURCES: Studies were identified from the Cochrane
      central register of controlled trials, the Oxford database of perinatal trials,
      PubMed, previous reviews, and abstracts. Review methods Reports that compared
      whole body cooling or selective head cooling with normal care in neonates with
      hypoxic-ischaemic encephalopathy and that included data on death or disability
      and on specific neurological outcomes of interest to patients and clinicians were
      selected. Results We found three trials, encompassing 767 infants, that included
      information on death and major neurodevelopmental disability after at least 18
      months' follow-up. We also identified seven other trials with mortality
      information but no appropriate neurodevelopmental data. Therapeutic hypothermia
      significantly reduced the combined rate of death and severe disability in the
      three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval
      0.71 to 0.93, P=0.002; risk difference -0.11, 95% CI -0.18 to -0.04), with a
      number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival
      with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001;
      risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of
      eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability
      (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental
      index of less than 70 (P=0.01 and P=0.02, respectively). No significant
      interaction between severity of encephalopathy and treatment effect was detected.
      Mortality was significantly reduced when we assessed all 10 trials (1320 infants;
      relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference -0.07, 95% CI 
      0.12 to -0.02), with a number needed to treat of 14 (95% CI 8 to 47).
      CONCLUSIONS: In infants with hypoxic-ischaemic encephalopathy, moderate
      hypothermia is associated with a consistent reduction in death and neurological
      impairment at 18 months.

PMID- 20144985
TI  - India decides to train non-medical rural healthcare providers.

PMID- 20144982
TI  - Hypoxic ischaemic encephalopathy in infants.

PMID- 20144987
TI  - Major changes are proposed for definitions of female sexual dysfunction.

PMID- 20144986
TI  - Withdrawal of sibutramine in Europe.

PMID- 20144988
TI  - Microtubule assembly by the Apc protein is regulated by importin-beta--RanGTP.
AB  - Mutations in the tumour suppressor Adenomatous polyposis coli (Apc) initiate most
      sporadic colorectal cancers. Apc is implicated in regulating microtubule (MT)
      dynamics in interphase and mitosis. However, little is known about the underlying
      mechanism or regulation of this Apc function. We identified importin-beta as a
      binding partner of Apc that regulates its effect on MTs. Apc binds importin-beta
      in vitro and in Xenopus egg extracts, and RanGTP inhibits this interaction. The
      armadillo-like repeat domain of importin-beta binds to the middle of Apc, where
      it can compete with beta-catenin. In addition, two independent sites in the C
      terminus of Apc bind the N-terminal region of importin-beta. Binding to importin
      beta reduces the ability of Apc to assemble and bundle MTs in vitro and to
      promote assembly of microtubule asters in Xenopus egg extracts, but does not
      affect the binding of Apc to MTs or to EB1. Depletion of Apc decreases the
      formation of cold-stable spindles in Xenopus egg extracts. Importantly, the
      ability of purified Apc to rescue this phenotype was reduced when it was
      constitutively bound to importin-beta. Thus, importin-beta binds to Apc and
      negatively regulates the MT-assembly and spindle-promoting activity of Apc in a
      Ran-regulatable manner.

PMID- 20144989
TI  - Centromere DNA decatenation depends on cohesin removal and is required for
      mammalian cell division.
AB  - Sister chromatid cohesion is mediated by DNA catenation and proteinaceous cohesin
      complexes. The recent visualization of PICH (Plk1-interacting checkpoint
      helicase)-coated DNA threads in anaphase cells raises new questions as to the
      role of DNA catenation and its regulation in time and space. In the present study
      we show that persistent DNA catenation induced by inhibition of Topoisomerase
      IIalpha can contribute to sister chromatid cohesion in the absence of cohesin
      complexes and that resolution of catenation is essential for abscission.
      Furthermore, we use an in vitro chromatid separation assay to investigate the
      temporal and functional relationship between cohesin removal and Topoisomerase
      IIalpha-mediated decatenation. Our data suggest that centromere decatenation can
      occur only after separase activation and cohesin removal, providing a plausible
      explanation for the persistence of centromere threads after anaphase onset.

PMID- 20144990
TI  - Fission yeast TORC1 regulates phosphorylation of ribosomal S6 proteins in
      response to nutrients and its activity is inhibited by rapamycin.
AB  - Cellular activities are regulated by environmental stimuli through protein
      phosphorylation. Target of rapamycin (TOR), a serine/threonine kinase, plays
      pivotal roles in cell proliferation and cell growth in response to nutrient
      status. In Schizosaccharomyces pombe, TORC1, which contains Tor2, plays crucial
      roles in nutrient response. Here we find a nitrogen-regulated phosphoprotein,
      p27, in S. pombe using the phospho-Akt substrate antibody. Response of p27
      phosphorylation to nitrogen availability is mediated by TORC1 and the TSC-Rhb1
      signaling, but not by TORC2 or other nutrient stress-related pathways. Database
      and biochemical analyses indicate that p27 is identical to ribosomal protein S6
      (Rps6). Ser235 and Ser236 in Rps6 are necessary for Rps6 phosphorylation by
      TORC1. These Rps6 phosphorylations are dispensable for cell viability. Rps6
      phosphorylation by TORC1 also responds to availability of glucose and is
      inhibited by osmotic and oxidative stresses. Rapamycin inhibits the ability of
      TORC1 to phosphorylate Rps6, owing to interaction of the rapamycin-FKBP12 complex
      with the FRB domain in Tor2. Rapamycin also leads to a decrease in cell size in a
      TORC1-dependent manner. Our findings demonstrate that the nutrient-responsive and
      rapamycin-sensitive TORC1-S6 signaling exists in S. pombe, and that this pathway
      plays a role in cell size control.

PMID- 20144991
TI  - Regulated increase in folding capacity prevents unfolded protein stress in the
      ER.
AB  - Stimulation of thyrocytes with thyroid stimulating hormone (TSH) leads to a
      morphological change and a massive increase in thyroglobulin (Tg) production.
      Although Tg is a demanding client of the endoplasmic reticulum (ER), its increase
      did not result in significant accumulation of unfolded protein in the ER.
      Instead, ER chaperones and folding enzymes reached maximum synthesis rates
      immediately after TSH stimulation, before significant upregulation of Tg
      synthesis. The resulting increase in folding capacity before client protein
      production prevented cellular unfolded-protein stress, confirmed by the silence
      of the most conserved branch of the unfolded protein response. Thyrocytes set an
      example of physiological adaptation of cells to a future potentially stress
      causing situation, which suggests a general strategy for both non-secretory and
      specialized secretory cells.

PMID- 20144992
TI  - Role of TI-VAMP and CD82 in EGFR cell-surface dynamics and signaling.
AB  - The v-SNARE TI-VAMP (VAMP7) mediates exocytosis during neuritogenesis,
      phagocytosis and lysosomal secretion. It localizes to endosomes and lysosomes but
      also to the trans-Golgi network. Here we show that depletion of TI-VAMP enhances
      the endocytosis of activated EGF receptor (EGFR) without affecting constitutive
      endocytosis of EGFR, or transferrin uptake. This increased EGFR internalization
      is mainly clathrin dependent. Searching for defects in EGFR regulators, we found
      that TI-VAMP depletion reduces the cell surface amount of CD82, a tetraspanin
      known to control EGFR localization in microdomains. We further show that TI-VAMP
      is required for secretion from the Golgi apparatus to the cell surface, and that
      TI-VAMP-positive vesicles transport CD82. Quantum dots video-microscopy indicates
      that depletion of TI-VAMP, or its cargo CD82, restrains EGFR diffusion and the
      area explored by EGFR at the cell surface. Both depletions also impair MAPK
      signaling and enhance endocytosis of activated EGFR by increased recruitment of
      AP-2. These results highlight the role of TI-VAMP in the secretory pathway of a
      tetraspanin, and support a model in which CD82 allows EGFR entry in microdomains
      that control its clathrin-dependent endocytosis and signaling.

PMID- 20144993
TI  - Control of mitotic and meiotic centriole duplication by the Plk4-related kinase
      ZYG-1.
AB  - Centriole duplication is of crucial importance during both mitotic and male
      meiotic divisions, but it is currently not known whether this process is
      regulated differently during the two modes of division. In Caenorhabditis
      elegans, the kinase ZYG-1 plays an essential role in both mitotic and meiotic
      centriole duplication. We have found that the C-terminus of ZYG-1 is necessary
      and sufficient for targeting to centrosomes and is important for differentiating
      mitotic and meiotic centriole duplication. Small truncations of the C-terminus
      dramatically lower the level of ZYG-1 at mitotic centrosomes but have little
      effect on the level of ZYG-1 at meiotic centrosomes. Interestingly, truncation of
      ZYG-1 blocks centrosome duplication in the mitotic cycle but leads to centrosome
      amplification in the meiotic cycle. Meiotic centriole amplification appears to
      result from the overduplication of centrioles during meiosis I and leads to the
      formation of multipolar meiosis II spindles. The extra centrioles also disrupt
      spermatogenesis by inducing the formation of supernumerary fertilization
      competent spermatids that contain abnormal numbers of chromosomes and centrioles.
      Our data reveal differences in the regulation of mitotic and meiotic centrosome
      duplication, particularly with regard to ZYG-1 activity, and reveal an important
      role for centrosomes in spermatid formation.

PMID- 20144994
TI  - Drosophila Klp67A binds prophase kinetochores to subsequently regulate
      congression and spindle length.
AB  - The kinesin-8 proteins are a family of microtubule-depolymerising motor
      molecules, which, despite their highly conserved roles in chromosome alignment
      and spindle dynamics, remain poorly characterised. Here, we report that the
      Drosophila kinesin-8 protein, Klp67A, exists in two spatially and functionally
      separable metaphase pools: at kinetochores and along the spindle. Fixed and live
      cell analyses of different Klp67A recombinant variants indicate that this kinesin
      8 first collects at kinetochores during prophase and, by metaphase, localises to
      the kinetochore outerplate. Although the catalytic motor activity of Klp67A is
      required for efficient kinetochore recruitment at all times, microtubules are
      entirely dispensable for this process. The tail of Klp67A does not play a role in
      kinetochore accumulation, but is both necessary and sufficient for spindle
      association. Using functional assays, we reveal that chromosome position and
      spindle length are determined by the microtubule-depolymerising motor activity of
      Klp67A exclusively when located at kinetochores, but not along the spindle. These
      data reveal that, unlike other metazoan kinesin-8 proteins, Klp67A binds the
      nascent prophase and mature metaphase kinetochore. From this location, Klp67A
      uses its motor activity to ensure chromosome alignment and proper spindle length.

PMID- 20144995
TI  - Integrins stimulate E-cadherin-mediated intercellular adhesion by regulating Src
      kinase activation and actomyosin contractility.
AB  - Cadherins and integrins are major adhesion molecules regulating cell-cell and
      cell-matrix interactions. In vitro and in vivo studies have demonstrated the
      existence of crosstalk between integrins and cadherins in cell adhesion and
      motility. We used a dual pipette assay to measure the force required to separate
      E-cadherin-producing cell doublets and to investigate the role of integrin in
      regulating the strength of intercellular adhesion. A greater force was required
      to separate cell doublets bound to fibronectin or vitronectin-coated beads than
      for doublets bound to polylysine-coated beads. This effect depended on cell
      spreading and the duration of stimulation. Cells expressing type II cadherin-7
      also responded to fibronectin stimulation to produce a higher intercellular
      adhesion. Establishment of cadherin-mediated adhesion needed ROCK, MLCK and
      myosin ATPase II activity. The regulation of intercellular adhesion strength by
      integrin stimulation required activation of Src family kinases, ROCK and
      actomyosin contractility. These findings highlight the importance and mechanisms
      of molecular crosstalk between cadherins and integrins in the control of cell
      plasticity during histogenesis and morphogenesis.

PMID- 20144998
TI  - Sensory reception is an attribute of both primary cilia and motile cilia.
AB  - A recent cluster of papers has shown that motile cilia in the respiratory and
      reproductive tracts of humans and other mammals can exhibit sensory functions, a
      function previously attributed primarily to non-motile primary cilia. This leads
      to a new paradigm that all cilia and flagella (both motile and primary) can
      mediate sensory functions. However, examination of the literature shows that
      evidence of sensory functions of motile cilia and flagella is widespread in
      studies of invertebrates, and extends as back as far as 1899. In this Opinion
      article, I review the recent and historical findings that motile cilia have a
      variety of sensory functions, and discuss how this concept has in fact been
      evolving for the past century.

PMID- 20144997
TI  - The primary cilium at a glance.

PMID- 20144999
TI  - The perennial organelle: assembly and disassembly of the primary cilium.
AB  - Primary cilia contain signaling receptors of diverse classes, and ciliary
      dysfunction results in a variety of developmental defects. Thus, primary cilia
      are thought to have an important role in sensing and transducing cellular
      signals. Although there is clear evidence demonstrating that these organelles are
      assembled and disassembled dynamically as cells progress through the cell cycle,
      the mechanisms by which the cell cycle controls the assembly and disassembly of
      the primary cilium remain poorly understood. In this Commentary, we review the
      basic cellular mechanisms that underlie the early stages of cilium assembly and
      discuss how the cell cycle communicates with the ciliation program. A commonly
      held view is that ciliation occurs exclusively in cells that have exited the cell
      cycle and entered quiescence or differentiation. However, this concept is at odds
      with the finding that, during development, many actively proliferating cells
      require cilia-mediated signaling pathways to instruct their developmental fate.
      Here, we reassess the quiescence-centric view of ciliation by reviewing historic
      and current literature. We discuss ample evidence that cilia are in fact present
      on many proliferating cells, and that a transient peak of ciliation before the G1
      S transition might be tightly coupled to entry into the DNA replication phase.
      Finally, we touch on the relationship between the ciliation and cell-division
      cycles and the tissue distribution of primary cilia in order to highlight
      potential roles for the primary cilium in restraining cells from the
      hyperproliferative state that contributes to cancer.

PMID- 20145000
TI  - Flagellar and ciliary beating: the proven and the possible.
AB  - The working mechanism of the eukaryotic flagellar axoneme remains one of nature's
      most enduring puzzles. The basic mechanical operation of the axoneme is now a
      story that is fairly complete; however, the mechanism for coordinating the action
      of the dynein motor proteins to produce beating is still controversial. Although
      a full grasp of the dynein switching mechanism remains elusive, recent
      experimental reports provide new insights that might finally disclose the secrets
      of the beating mechanism: the special role of the inner dynein arms, especially
      dynein I1 and the dynein regulatory complex, the importance of the dynein
      microtubule-binding affinity at the stalk, and the role of bending in the
      selection of the active dynein group have all been implicated by major new
      evidence. This Commentary considers this new evidence in the context of various
      hypotheses of how axonemal dynein coordination might work.

PMID- 20145001
TI  - Molecular mechanisms of protein and lipid targeting to ciliary membranes.
AB  - Cilia are specialized surface regions of eukaryotic cells that serve a variety of
      functions, ranging from motility to sensation and to regulation of cell growth
      and differentiation. The discovery that a number of human diseases, collectively
      known as ciliopathies, result from defective cilium function has expanded
      interest in these structures. Among the many properties of cilia, motility and
      intraflagellar transport have been most extensively studied. The latter is the
      process by which multiprotein complexes associate with microtubule motors to
      transport structural subunits along the axoneme to and from the ciliary tip. By
      contrast, the mechanisms by which membrane proteins and lipids are specifically
      targeted to the cilium are still largely unknown. In this Commentary, we review
      the current knowledge of protein and lipid targeting to ciliary membranes and
      outline important issues for future study. We also integrate this information
      into a proposed model of how the cell specifically targets proteins and lipids to
      the specialized membrane of this unique organelle.

PMID- 20145002
TI  - Drosophila Rel proteins are central regulators of a robust, multi-organ immune
      network.
AB  - Survival of all animals depends on effective protection against infection. In
      Drosophila, opportunistic infection kills larvae if they lack the Rel/NF-kappaB
      proteins Dorsal and Dif. We have used tissue-specific expression of Dif and
      Dorsal to reveal that these Rel proteins act in three different tissues to defend
      larvae from infection. Dif and Dorsal act in circulating blood cells, where they
      are required autonomously to promote blood-cell survival and phagocytosis of
      microorganisms. We show that a major transcriptional target of Dorsal and Dif in
      blood cells is Drosophila IAP1, a gene protecting these cells from death. We find
      that in addition to their autonomous role in blood-cell survival, Dif and Dorsal
      also act in the fat body to produce factors that promote blood-cell viability.
      These Rel proteins act in the epidermis to prevent infection by maintaining a
      barrier to microbial entry. Dorsal or Dif in any one of the three tissues is
      sufficient to defend the animal from opportunistic infection. Thus Drosophila has
      a multi-pronged system of defense and each branch of this network requires Rel
      proteins. Based on similarities between Drosophila and mammals, we propose that a
      Rel-dependent network is an ancient and robust framework of animal immune
      systems.

PMID- 20145003
TI  - Red (anthocyanic) leaf margins do not correspond to increased phenolic content in
      New Zealand Veronica spp.
AB  - BACKGROUND AND AIMS: Red or purple coloration of leaf margins is common in
      angiosperms, and is found in approx. 25 % of New Zealand Veronica species.
      However, the functional significance of margin coloration is unknown. We
      hypothesized that anthocyanins in leaf margins correspond with increased phenolic
      content in leaf margins and/or the leaf entire, signalling low palatability or
      leaf quality to edge-feeding insects. METHODS: Five species of Veronica with red
      leaf margins, and six species without, were examined in a common garden. Phenolic
      content in leaf margins and interior lamina regions of juvenile and fully
      expanded leaves was quantified using the Folin-Ciocalteu assay. Proportions of
      leaf margins eaten and average lengths of continuous bites were used as a proxy
      for palatability. KEY RESULTS: Phenolic content was consistently higher in leaf
      margins compared with leaf interiors in all species; however, neither leaf
      margins nor more interior tissues differed significantly in phenolic content with
      respects to margin colour. Mean phenolic content was inversely correlated with
      the mean length of continuous bites, suggesting effective deterrence of grazing.
      However, there was no difference in herbivore consumption of red and green
      margins, and the plant species with the longest continuous grazing patterns were
      both red-margined. CONCLUSIONS: Red margin coloration was not an accurate
      indicator of total phenolic content in leaf margins or interior lamina tissue in
      New Zealand Veronica. Red coloration was also ineffective in deterring herbivory
      on the leaf margin, though studies controlling for variations in leaf structure
      and biochemistry (e.g. intra-specific studies) are needed before more precise
      conclusions can be drawn. It is also recommended that future studies focus on the
      relationship between anthocyanin and specific defence compounds (rather than
      general phenolic pools), and evaluate possible alternative functions of red
      margins in leaves (e.g. antioxidants, osmotic adjustment).

PMID- 20145004
TI  - Shared lesbian motherhood: a challenge of established concepts and frameworks.

PMID- 20145005
TI  - Sharing motherhood: biological lesbian co-mothers, a new IVF indication.
AB  - BACKGROUND: We herein present the initial experiences of the CEFER Institute of
      Reproduction in the formation of a new family model: two biological mothers,
      lesbians, one who provides the eggs and the other who carries the embryo in her
      womb. We have called this family model ROPA (Reception of Oocytes from PArtner).
      It is a pioneer event in Spain and among the first at a worldwide level. METHODS
      AND RESULTS: Fourteen lesbian couples have undergone treatment using the ROPA
      technique. This paper briefly describes the technique. Six pregnancies have been
      obtained from 13 embryo transfers. There were two miscarriages and there are
      three ongoing pregnancies, one of them twins. One healthy female baby was born.
      The following aspects are addressed: (i) legal status of lesbian couples in
      Western countries; (ii) the lesbian couple's access to assisted reproduction
      techniques; (iii) ethical aspects; (iv) medical acceptability; and (v) single
      mother versus lesbian mothers. CONCLUSIONS: In countries where the ROPA technique
      is legal, it offers lesbian couples a more favourable route, involving both
      partners, to start a family, and doctors who treat lesbian couples must be
      sensitive to this new family model.

PMID- 20145006
TI  - Evolutionary lineages and functional diversification of plant hexokinases.
AB  - Sequencing data from 10 species show that a plant hexokinase (HXK) family
      contains 5-11 genes. Functionally, a given family can include metabolic
      catalysts, glucose signaling proteins, and non-catalytic, apparent regulatory
      enzyme homologs. This study has two goals. The first aim is to develop a
      predictive method to determine which HXK proteins within a species have which
      type of function. The second aim is to determine whether HXK-dependent glucose
      signaling proteins occur among more primitive plants, as well as among
      angiosperms. Using a molecular phylogeny approach, combined with selective
      experimental testing, we found that non-catalytic HXK homologs might occur in all
      plants, including the relatively primitive Selaginella moellendorffi. We also
      found that different lineages of angiosperm HXKs have apparent conserved features
      for catalytic activity and for sub-cellular targeting. Most higher-plant HXKs are
      expressed predominantly at mitochondria, with HXKs of one lineage occurring in
      the plastid, and HXKs of one monocot lineage occurring in the cytosol. Using
      protoplast transient expression assays, we found that HXK glucose signaling
      proteins occur likely in all higher plants and in S. moellendorffi as well. Thus,
      the use of glucose by plant HXK isoforms in metabolism and/or as a regulatory
      metabolite occurs as widespread, conserved processes.

PMID- 20145007
TI  - Low-valency, but not monovalent, antigens trigger the B-cell antigen receptor
      (BCR).
AB  - Antigen binding to the B-cell antigen receptor (BCR) leads to receptor triggering
      and B-lymphocyte activation. Here, we have probed the molecular requirements for
      BCR triggering in primary murine B cells using a set of defined soluble
      haptenated peptides. Bi- and trivalent haptens activated the BCR, as measured by
      protein phosphorylation, Ca(2+) influx, BCR down-modulation and CD69, CD86 and
      MHC class II up-regulation. In contrast, four distinct monovalent haptens were
      ineffective. Next, we used two different anti-idiotypic antibodies, which bind to
      the antigen-combining site of the BCR. Again, monovalent Fab fragments were
      ineffective, whereas bivalent antibodies could stimulate the BCR. These findings
      are compatible with ligand-induced clustering of monomeric BCRs or re
      organization of BCR complexes within pre-formed BCR oligomers. Lastly, an
      increase in the valency of the haptenated peptides improved the activation
      potential, whereas variations in the distance between two haptens had no effect.
      This finding contributes to understand how the immune system can efficiently
      recognize structurally diverse antigens but still discriminate between foreign
      and self.

PMID- 20145008
TI  - Re: "effect of supplemental folic acid in pregnancy on childhood asthma: a
      prospective birth cohort study".

PMID- 20145009
TI  - Physical activity, sedentary behavior and depression among disadvantaged women.
AB  - This study investigated associations between components of physical activity (PA;
      e.g. domain and social context) and sedentary behaviors (SBs) and risk of
      depression in women from disadvantaged neighborhoods. A total of 3645 women, aged
      18-45 years, from disadvantaged neighborhoods, self-reported their PA, SB and
      depressive symptoms. Crude and adjusted odds ratios and 95% confidence intervals
      were calculated for each component of PA, SB and risk of depression using
      logistic regression analyses, adjusting for clustering by women's neighborhood of
      residence. Being in a higher tertile of leisure-time PA and transport-related PA
      was associated with lower risk of depression. No associations were apparent for
      domestic or work-related PA. Women who undertook a small proportion of their
      leisure-time PA with someone were less likely to be at risk of depression than
      those who undertook all leisure-time PA on their own. Women reporting greater
      time sitting at the computer, screen time and overall sitting time had higher
      odds of risk of depression compared with those reporting low levels. The domain
      and social context of PA may be important components in reducing the risk of
      depression. Reducing time spent in SB may be a key strategy in the promotion of
      better mental health in women from disadvantaged neighborhoods.

PMID- 20145012
TI  - Excluding medical and haematological conditions as a cause of bruising in
      suspected non-accidental injury.
AB  - A mistaken diagnosis of child abuse can occur in a number of medical conditions,
      many of which can be readily diagnosed by experienced paediatricians. Bleeding
      disorders offer a greater challenge, especially when court proceedings may demand
      their exclusion. Some of these disorders are rare but more prevalent in areas
      which have a high incidence of consanguinity. We advocate two stages of
      laboratory investigations but the limitations of some of these tests and their
      inability to exclude a bleeding disorder with absolute certainty should be
      recognised. However, if personal and family histories are absent and both first
      stage and second-stage investigations are normal, it is highly unlikely that a
      bleeding disorder will be missed.

PMID- 20145010
TI  - Modulation of microRNA expression by budesonide, phenethyl isothiocyanate and
      cigarette smoke in mouse liver and lung.
AB  - Although microRNAs (miRNA) have extensively been investigated in cancer research,
      less attention has been paid to their regulation by carcinogens and/or protective
      factors in early stages of the carcinogenesis process. The present study was
      designed to evaluate the modulation of mRNA expression as related to exposure of
      neonatal mice to environmental cigarette smoke (ECS) and to treatment with
      chemopreventive agents. Exposure to ECS started immediately after birth and for 2
      weeks after weaning. Thereafter, groups of mice received daily either budesonide
      (BUD) or phenethyl isothiocyanate (PEITC) with the diet. The expression of 576
      miRNAs was evaluated by miRNA microarray in liver and lung. In sham-exposed mice,
      the expression of miRNAs tended to be higher in liver than in lung. ECS
      downregulated the expression of a number of miRNAs in lung, whereas mixed
      alterations were observed in liver. PEITC and BUD did not substantially affect
      the physiological situation in lung, whereas both agents caused intense
      variations in liver, reflecting the occurrence of damage mechanisms, such as
      inflammation, DNA and protein damage, cellular stress, proliferation and
      apoptosis. PEITC and BUD protected the lung from ECS-induced alterations of miRNA
      expression but exhibited some adverse effects in liver.

PMID- 20145013
TI  - Management of suspected appendicitis in children.
AB  - Acute appendicitis is the most important cause of abdominal pain in children and
      is the commonest that requires emergency surgery. Prompt diagnosis, immediate
      referral and expeditious surgery should be undertaken to reduce the risk of a
      perforated appendix. The initial presentation may be atypical or be similar to
      another pathological process which makes the diagnosis extremely difficult. Risk
      assessment forms an important part in the management of these cases. We consider
      the difficulties in making the diagnosis including: (A) the pitfalls of clinical
      examination; (B) the usefulness of laboratory testing; (C) the relevance of
      clinical scoring systems; and (D) the controversial issue of imaging.

PMID- 20145014
TI  - Investigation of the child with permanent hearing impairment.

PMID- 20145015
TI  - NICE guideline: attention deficit hyperactivity disorder.

PMID- 20145016
TI  - Evaluation - the educational context.
AB  - Evaluation comes in many shapes and sizes. It can be as simple and as grounded in
      day to day work as a clinical teacher reflecting on a lost teaching opportunity
      and wondering how to do it better next time or as complex, top down and
      politically charged as a major government led evaluation of use of teaching funds
      with the subtext of re-allocating them. Despite these multiple spectra of scale,
      perceived ownership, financial and political implications, the underlying
      principles of evaluation are remarkably consistent. To evaluate well, it needs to
      be clear who is evaluating what and why. From this will come notions of how it
      needs to be done to ensure the evaluation is meaningful and useful. This paper
      seeks to illustrate what evaluation is, why it matters, where to start if you
      want to do it and how to deal with evaluation that is external and imposed.

PMID- 20145017
TI  - Mobility in older adults: a comprehensive framework.
AB  - Mobility is fundamental to active aging and is intimately linked to health status
      and quality of life. Although there is widespread acceptance regarding the
      importance of mobility in older adults, there have been few attempts to
      comprehensively portray mobility, and research has to a large extent been
      discipline specific. In this article, a new theoretical framework for mobility is
      presented with the goals of raising awareness of the complexity of factors that
      influence mobility and stimulating new integrative and interdisciplinary research
      ideas. Mobility is broadly defined as the ability to move oneself (e.g., by
      walking, by using assistive devices, or by using transportation) within community
      environments that expand from one's home, to the neighborhood, and to regions
      beyond. The concept of mobility is portrayed through 5 fundamental categories of
      determinants (cognitive, psychosocial, physical, environmental, and financial),
      with gender, culture, and biography (personal life history) conceptualized as
      critical cross-cutting influences. Each category of determinants consists of an
      increasing number of factors, demonstrating greater complexity, as the mobility
      environment expands farther from the home. The framework illustrates how mobility
      impairments can lead to limitations in accessing different life-spaces and
      stresses the associations among determinants that influence mobility. By bridging
      disciplines and representing mobility in an inclusive manner, the model suggests
      that research needs to be more interdisciplinary and current mobility findings
      should be interpreted more comprehensively, and new more complex strategies
      should be developed to address mobility concerns.

PMID- 20145018
TI  - The mismatch repair system modulates curcumin sensitivity through induction of
      DNA strand breaks and activation of G2-M checkpoint.
AB  - The highly conserved mismatch (MMR) repair system corrects postreplicative errors
      and modulates cellular responses to genotoxic agents. Here, we show that the MMR
      system strongly influences cellular sensitivity to curcumin. Compared with MMR
      proficient cells, isogenically matched MMR-deficient cells displayed enhanced
      sensitivity to curcumin. Similarly, cells suppressed for MLH1 or MSH2 expression
      by RNA interference displayed increased curcumin sensitivity. Curcumin treatment
      generated comparable levels of reactive oxygen species and the mutagenic adduct 8
      oxo-guanine in MMR-proficient and MMR-deficient cells; however, accumulation of
      gammaH2AX foci, a marker for DNA double-strand breaks (DSB), occurred only in MMR
      positive cells in response to curcumin treatment. Additionally, MMR-positive
      cells showed activation of Chk1 and induction of G(2)-M cell cycle checkpoint
      following curcumin treatment and inhibition of Chk1 by UCN-01 abrogated Chk1
      activation and heightened apoptosis in MMR-proficient cells. These results
      indicate that curcumin triggers the accumulation of DNA DSB and induction of a
      checkpoint response through a MMR-dependent mechanism. Conversely, in MMR
      compromised cells, curcumin-induced DSB is significantly blunted, and as a
      result, cells fail to undergo cell cycle arrest, enter mitosis, and die through
      mitotic catastrophe. The results have potential therapeutic value, especially in
      the treatment of tumors with compromised MMR function.

PMID- 20145019
TI  - Proanthocyanidins inhibit in vitro and in vivo growth of human non-small cell
      lung cancer cells by inhibiting the prostaglandin E(2) and prostaglandin E(2)
      receptors.
AB  - Overexpression of cyclooxygenase-2 (COX-2) and prostaglandins (PG) is linked to a
      wide variety of human cancers. Here, we assessed whether the chemotherapeutic
      effect of grape seed proanthocyanidins (GSP) on non-small cell lung cancer
      (NSCLC) cells is mediated through the inhibition of COX-2 and PGE(2)/PGE(2)
      receptor expression. The effects of GSPs on human NSCLC cell lines in terms of
      proliferation, apoptosis, and expression of COX-2, PGE(2), and PGE(2) receptors
      were determined using Western blotting, fluorescence-activated cell sorting
      analysis, and reverse transcription-PCR. In vitro treatment of NSCLC cells (A549,
      H1299, H460, H226, and H157) with GSPs resulted in significant growth inhibition
      and induction of apoptosis, which were associated with the inhibitory effects of
      GSPs on the overexpression of COX-2, PGE(2), and PGE(2) receptors (EP1 and EP4)
      in these cells. Treatment of cells with indomethacin, a pan-COX inhibitor, or
      transient transfection of cells with COX-2 small interfering RNA, also inhibited
      cell growth and induced cell death. The effects of a GSP-supplemented AIN76A
      control diet fed to nude mice bearing tumor xenografts on the expression of COX
      2, PGE(2), and PGE(2) receptors in the xenografts were also evaluated. The growth
      inhibitory effect of dietary GSPs (0.5%, w/w) on the NSCLC xenograft tumors was
      associated with the inhibition of COX-2, PGE(2), and PGE(2) receptors (EP1, EP3,
      and EP4) in tumors. This preclinical study provides evidence that the
      chemotherapeutic effect of GSPs on lung cancer cells in vitro and in vivo is
      mediated, at least in part, through the inhibition of COX-2 expression and
      subsequently the inhibition of PGE(2) and PGE(2) receptors.

PMID- 20145020
TI  - Binding of sulphatide to recombinant haemagglutinin of influenza A virus produced
      by a baculovirus protein expression system.
AB  - Association of sulphatide with influenza A virus (IAV) haemagglutinin (HA)
      delivered to the cell surface promotes progeny virus production. However, it is
      not known whether there is direct binding of HA to sulphatide. In this study, we
      found that recombinant HA, which was produced by a baculovirus protein expression
      system from the HA gene of A/duck/HK/313/4/78 (H5N3), bound to sulphatide in a
      dose-dependent manner and that the binding was inhibited by a specific antibody.
      Our results indicate that the recombinant HA is useful for elucidation of the
      binding domain of HA with sulphatide and for the development of new anti-IAV
      agents.

PMID- 20145021
TI  - Designed horizontal transfer of stable giant DNA released from Escherichia coli.
AB  - DNA in the environment is a source to mediate horizontal gene transfer (HGT).
      Present molecular cloning methods are based on this HGT principle. However, DNA
      in the extracellular environment, particularly with high molecular-weight, is
      thought to be prone to shearing or digestion by nucleases. Here we discovered
      that extracellular plasmid DNA released from lysed Escherichia coli remained
      intact and stable. Furthermore, it was demonstrated that plasmids up to 100 kb in
      size were taken up by co-present competent Bacillus subtilis cells. The detailed
      kinetics of the process together with sensitivity to added DNase I indicated that
      plasmid DNA released from lysed E. coli into the culture medium was stable enough
      for quantitative efficacy in the transformation of B. subtilis. Our results will
      be useful for the development of methods to transfer giant DNAs from general host
      E. coli without their biochemical purification.

PMID- 20145022
TI  - Measuring case complexity in neurological rehabilitation.

PMID- 20145023
TI  - Roll on genetics of PARK and Parkinsonism in the developing world.

PMID- 20145024
TI  - Anticholinergic activity and cognitive decline in Parkinson's disease.

PMID- 20145025
TI  - Awake seizures after pure sleep-related epilepsy: a systematic review and
      implications for driving law.
AB  - Who with sleep seizures is safe to drive? Driving law is controversial;
      ineligibility varies between individual US states and EU countries. Current UK
      driving law is strongly influenced by a single-centre study from 1974 where most
      participants were not taking antiepileptic drugs (AEDs). However, pure sleep
      related epilepsy is often fully controlled on medication, and its withdrawal can
      provoke awake seizures. This systematic review asked, 'What is the risk of awake
      seizures in pure sleep-related epilepsy?' 9885 titles were identified; 2312 were
      excluded (not human or adult); 40 full texts were reviewed; six papers met our
      inclusion criteria; each of these six studies had a different pure sleep-related
      epilepsy definition. Using the largest prospective study, we were able to
      calculate next year's awake seizure chance (treated with antiepileptic
      medication). This was maximal in the second year: 5.7% (95% CI 3.0 to 10.4%).
      European licensing bodies including the UK's Driver and Vehicle Licensing Agency
      broadly accept a risk of less than 20% for Group 1 licensing. However, this study
      excluded patients with frontal-lobe epilepsies. Furthermore, follow-up (n=160)
      varied from 2 to 6 years, yet new awake seizures may occur even after 10-20 years
      of pure sleep-related epilepsy A paucity of evidence underpins present licensing
      law; current rulings would be difficult to defend if legally challenged. The law
      may be penalising people with pure sleep-related epilepsy without increased risk
      of awake seizures, while failing to identify subgroups at unacceptable risk of an
      awake seizure at the wheel.

PMID- 20145026
TI  - Individual white matter fractional anisotropy analysis on patients with MRI
      negative partial epilepsy.
AB  - BACKGROUND: Conventional structural MRI fails to identify a cerebral lesion in
      25% of patients with cryptogenic partial epilepsy (CPE). Diffusion tensor imaging
      is an MRI technique sensitive to microstructural abnormalities of cerebral white
      matter (WM) by quantification of fractional anisotropy (FA). The objectives of
      the present study were to identify focal FA abnormalities in patients with CPE
      who were deemed MRI negative during routine presurgical evaluation. METHODS:
      Diffusion tensor imaging at 3 T was performed in 12 patients with CPE and normal
      conventional MRI and in 67 age matched healthy volunteers. WM integrity was
      compared between groups on the basis of automated voxel-wise statistics of FA
      maps using an analysis of covariance. Volumetric measurements from high
      resolution T1-weighted images were also performed. RESULTS: Significant FA
      reductions in WM regions encompassing diffuse areas of the brain were observed
      when all patients as a group were compared with controls. On an individual basis,
      voxel based analyses revealed widespread symmetrical FA reduction in CPE
      patients. Furthermore, asymmetrical temporal lobe FA reduction was consistently
      ipsilateral to the electroclinical focus. No significant correlations were found
      between FA alterations and clinical data. There were no differences in brain
      volumes of CPE patients compared with controls. CONCLUSION: Despite normal
      conventional MRI, WM integrity abnormalities in CPE patients extend far beyond
      the epileptogenic zone. Given that unilateral temporal lobe FA abnormalities were
      consistently observed ipsilateral to the seizure focus, analysis of temporal FA
      may provide an informative in vivo investigation into the localisation of the
      epileptogenic zone in MRI negative patients.

PMID- 20145027
TI  - Utilisation behaviour in frontotemporal dementia.
AB  - OBJECTIVE: To study the occurrence of utilisation behaviour (UB) in patients with
      frontotemporal dementia (FTD). MATERIALS AND METHODS: Twenty patients who
      fulfilled all core Consensus statement criteria for FTD were examined by a
      neurologist experienced in dementia and by a clinical neuropsychologist. All
      patients had imaging evidence of predominantly frontal or frontotemporal
      involvement. Behavioural data were obtained from care givers using a
      semistructured questionnaire. Questions related to UB were asked in detail.
      Further assessment for UB was done during the interview with the patient using
      common objects. Only frank and coherent UB was considered for the study. For
      comparison, 34 patients with probable Alzheimer's disease diagnosed by the NINCDS
      ADRDA criteria were also similarly studied. RESULTS: 80 per cent of our patients
      with FTD but none with probable Alzheimer's disease exhibited UB. Fourteen out of
      the 16 patients with FTD who exhibited UB were less than 70 years old. Among
      patients with UB, 88% exhibited a wide range of 'incidental' UB. Objects of daily
      use tended to trigger UB most commonly. Utilisation behaviour tended to
      correspond to premorbid habits in at least 75% of our patients. CONCLUSION:
      Utilisation behaviour may be more common in FTD patients than is currently
      recognised. The presence of UB should be queried in every patient suspected to be
      suffering from FTD. A comprehensive questionnaire for UB such as that used here
      could be useful.

PMID- 20145028
TI  - Attention deficits in Alzheimer's disease and vascular dementia.
AB  - OBJECTIVE: To compare the performance of patients with mild-moderate Alzheimer's
      disease (AD) and vascular dementia (VaD) on tests of information processing and
      attention. METHOD: Patients with AD (n=75) and VaD (n=46) were recruited from a
      memory clinic along with dementia-free participants (n=28). They underwent
      specific tests of attention from the Cognitive Drug Research battery, and pen and
      paper tests including Colour Trails A and B and Stroop. All patients had a CT
      brain scan that was independently scored for white-matter change/ischaemia.
      RESULTS: Attention was impaired in both AD and VaD patients. VaD patients had
      more impaired choice reaction times and were less accurate on a vigilance test
      measuring sustained attention. Deficits in selective and divided attention
      occurred in both patient groups and showed the strongest correlations with Mini
      Mental State Examination scores. CONCLUSION: This study demonstrates problems
      with the attentional network in mild-moderate AD and VaD. The authors propose
      that attention should be tested routinely in a memory clinic setting.

PMID- 20145029
TI  - Neurological pictures. Atherosclerosis in congenital azygous solitary A2 anterior
      cerebral artery with simultaneous bifrontal infarctions.

PMID- 20145030
TI  - Neurological pictures. Primary Sjogren syndrome presenting as neuromyelitis
      optica.

PMID- 20145031
TI  - Late-onset Huntington disease with intermediate CAG repeats: true or false?
AB  - Huntington disease (HD) is a neurodegenerative disorder associated with an
      expanded CAG trinucleotide repeat length in the huntingtin gene. 'Intermediate
      alleles' with 27 to 35 CAG repeats generally do not cause HD but are unstable
      upon germ-line transmission. Insights in CAG repeat mosaicism and enhanced
      trinucleotide expansion in postmitotic neurons indicate that in the intermediate
      range, other factors than the CAG repeat length in diagnostic tests have to be
      considered. Here, we report two patients with mild, late onset HD and an
      intermediate repeat allele. The authors anticipate that intermediate repeats can
      cause late-onset HD due to disease modifiers and may be more common than
      previously stated.

PMID- 20145032
TI  - Phosphorylation of p53 serine 18 upregulates apoptosis to suppress Myc-induced
      tumorigenesis.
AB  - ATM and p53 are critical regulators of the cellular DNA damage response and
      function as potent tumor suppressors. In cells undergoing ionizing radiation, ATM
      is activated by double-strand DNA breaks and phosphorylates the NH(2) terminus of
      p53 at serine residue 18. We have previously generated mice bearing an amino acid
      substitution at this position (p53S18A) and documented a role for p53
      phosphorylation in DNA damage-induced apoptosis. In this present study, we have
      crossed E mu myc transgenic mice with our p53S18A mice to explore a role for ATM
      p53 signaling in response to oncogene-induced tumorigenesis. Similar to DNA
      damage induced by ionizing radiation, expression of c-Myc in pre-B cells induces
      p53 serine 18 phosphorylation and Puma expression to promote apoptosis. E mu myc
      transgenic mice develop B-cell lymphoma more rapidly when heterozygous or
      homozygous for p53S18A alleles. However, E mu myc-induced tumorigenesis in
      p53S18A mice is slower than that observed in E mu myc mice deficient for either
      p53 or ATM, indicating that both p53-induced apoptosis and p53-induced growth
      arrest contribute to the suppression of B-cell lymphoma formation in E mu myc
      mice. These findings further reveal that oncogene expression and DNA damage
      activate the same ATM-p53 signaling cascade in vivo to regulate apoptosis and
      tumorigenesis.

PMID- 20145034
TI  - Repression of human telomerase reverse transcriptase using artificial zinc finger
      transcription factors.
AB  - Telomerase activation is a key step in the development of human cancers.
      Expression of the catalytic subunit, human telomerase reverse transcriptase
      (hTERT), represents the limiting factor for telomerase activity. In this study,
      we have used artificial zinc finger protein (ZFP) transcription factors (TF) to
      repress the expression of hTERT in human cancer cell lines at the transcriptional
      level. We have constructed four-fingered ZFPs derived from the human genome which
      binds 12-bp recognition sequences within the promoter of the hTERT gene and fused
      them with a KRAB repressor domain to create a potent transcriptional repressor.
      Luciferase activity was decreased by >80% in all of the transcriptional
      repressors with luciferase reporter assay. When they were transfected into the
      telomerase-positive HEK293 cell line, a decrease of mRNA level and telomerase
      activity together with shortening of telomere length was observed. Actual growth
      of HEK293 cells was also inhibited by transfection of artificial ZFP-TFs. The
      repression was maintained for 100 days of culture. The repression of telomerase
      expression by artificial ZFP-TFs targeting the promoter region of the hTERT
      presents a new promising strategy for inhibiting the growth of human cancer
      cells.

PMID- 20145033
TI  - Cyclooxygenase-2 is a novel transcriptional target of the nuclear EGFR-STAT3 and
      EGFRvIII-STAT3 signaling axes.
AB  - Emerging evidence indicates a novel mode of epidermal growth factor receptor
      (EGFR) signaling, notably, one involves EGFR nuclear translocalization and
      subsequent gene activation. To date, however, the significance of the nuclear
      EGFR pathway in glioblastoma (GBM) is unknown. Here, we report that EGFR and its
      constitutively activated variant EGFRvIII undergo nuclear translocalization in
      GBM cells, in which the former event requires EGF stimulation and the latter is
      constitutive. To gain insights into the effect of nuclear EGFR on gene expression
      in GBM, we created isogenic GBM cell lines, namely, U87MG-vector, U87MG-EGFR, and
      U87MG-EGFRdNLS that, respectively, express the control vector, EGFR, and nuclear
      entry-defective EGFR with a deletion of the nuclear localization signal (NLS).
      Microarray analysis shows that 19 genes, including cyclooxygenase-2 (COX-2), to
      be activated in U87MG-EGFR cells but not in U87MG-EGFRdNLS and U87MG-vector
      cells. Subsequent validation studies indicate that COX-2 gene is expressed at
      higher levels in cells with EGFR and EGFRvIII than those with EGFRdNLS and
      EGFRvIIIdNLS. Nuclear EGFR and its transcriptional cofactor signal transducer and
      activator of transcription 3 (STAT3) associate with the COX-2 promoter. Increased
      expression of EGFR/EGFRvIII and activated STAT3 leads to the synergistic
      activation of the COX-2 promoter. Promoter mutational analysis identified a
      proximal STAT3-binding site that is required for EGFR/EGFRvIII-STAT3-mediated COX
      2 gene activation. In GBM tumors, an association exists between levels of COX-2,
      EGFR/EGFRvIII, and activated STAT3. Together, these findings indicate the
      existence of the nuclear EGFR/EGFRvIII signaling pathway in GBM and its
      functional interaction with STAT3 to activate COX-2 gene expression, thus linking
      EGFR-STAT3 and EGFRvIII-STAT3 signaling axes to proinflammatory COX-2 mediated
      pathway.

PMID- 20145035
TI  - targeted drug delivery to hepatocarcinoma in vivo by phage-displayed specific
      binding peptide.
AB  - Hepatocellular carcinoma is one of the deadliest cancers in the world. In this
      study, a hepatocarcinoma-specific binding peptide, which could be used for drug
      delivery in targeting therapy, was obtained by in vivo phage display technology.
      After three rounds of panning, only the potential motif Pro-Ser was found in 80
      sequenced phage clones. Phage A54 (sequence AGKGTPSLETTP) was shown to be the
      most effective and specific to the liver cancer cells by cell-based ELISA in all
      130 tested clones. After phage A54 was injected i.v. into the xenograft-bearing
      mice for in vivo distribution, phage enrichment was found in tumor tissues
      compared with control phage C10 and normal liver tissues through phage titering
      and immunohistochemical staining. Next, the specific binding ability of
      synthesized peptide A54 was further confirmed by fluorescence microscopy,
      competition binding, and fluorescence-activated cell sorting assay. A54 and A54M
      (sequence AGKGTAALETTP) were synthesized and coupled to doxorubicin (DOX) to do
      the preliminary targeting therapy. After the treatment, the proliferation of
      liver cancer cells treated with A54-DOX was restrained significantly in vitro
      when compared with A54M-DOX-treated group. Reduction in tumor size and
      prolongation of long-term survival were also found in xenograft-bearing models
      compared with free DOX-treated group. In conclusion, the specific binding peptide
      A54, which was screened from phage display library, represents a promising
      approach for the development of novel target therapy strategies against
      hepatocellular carcinoma.

PMID- 20145037
TI  - Sec5 and Exo84 foster oncogenic ras-mediated tumorigenesis.
AB  - The genes encoding the Ras family of small GTPases are mutated to yield
      constitutively active GTP-bound oncogenic proteins in one third of all human
      cancers. Oncogenic Ras binds to and activates a number of proteins that promote
      tumorigenic phenotypes, including the family of Ral guanine nucleotide exchange
      factors (RalGEF). Activated RalGEFs convert the Ral family of small GTPases,
      composed of RalA and RalB, from an inactive GDP-bound state to an active GTP
      bound state. As both RalA and RalB have been implicated in a variety of
      tumorigenic phenotypes, we sought to determine which proteins downstream of Rals
      promote transformation and tumorigenesis. Here, we report that shRNA-mediated
      knockdown of the Ral effector proteins Sec5 and Exo84, but less so in the case of
      RalBP1, reduced oncogenic RalGEF-mediated transformation and oncogenic Ras-driven
      tumorigenic growth of human cells. These results suggest that Rals promote
      oncogenic Ras-mediated tumorigenesis through, at least in part, Sec5 and Exo84.

PMID- 20145038
TI  - Urinary-type plasminogen activator receptor/alpha 3 beta 1 integrin signaling,
      altered gene expression, and oral tumor progression.
AB  - Oral squamous cell carcinoma (OSCC) has 50% 5-year survival rate, highlighting
      our limited understanding of the molecular events that contribute to disease
      progression. Microarray analyses of primary oral tumors have identified urinary
      type plasminogen activator (uPA) and its receptor (uPAR) as key genes associated
      with human OSCC progression. The uPAR functions as both a proteinase receptor and
      an integrin ligand, modifying proteolysis, migration, integrin signaling, and
      cellular transcription. In the current study, uPAR expression levels were
      modified in OSCC cells followed by analysis of tumor growth in an in vivo
      orthotopic xenograft model and by transcriptional profiling. Overexpression of
      uPAR resulted in more infiltrative and less differentiated tumors, with ill
      defined borders, cytologic atypia, and enhanced vascularity. Analysis of serial
      sections of both murine experimental tumors and microarrayed human OSCC showed a
      statistically significant association between uPAR and alpha(3) integrin
      colocalization in areas exhibiting extracellular signal-regulated kinase
      phosphorylation, suggesting that uPAR/alpha(3) integrin interaction potentiates
      extracellular signal-regulated kinase signaling in vivo. This is supported by
      cDNA microarray analysis, which showed differential expression of 148 genes (113
      upregulated and 35 downregulated). Validation of gene expression changes in human
      OSCC using immunohistochemistry and quantitative real-time PCR showed increased
      growth factors, proteinases/inhibitors, and matrix components in uPAR
      overexpressing tumors. Together, these results support a model wherein increased
      uPAR expression promotes alpha(3)beta(1) integrin association, resulting in
      increased mitogen-activated protein kinase signaling and transcriptional
      activation, leading to the formation of more aggressive tongue tumors. This
      combined approach has efficacy to identify additional biomarkers and/or
      prognostic indicators associated with aggressive human OSCC.

PMID- 20145039
TI  - Bcl-2 overexpression induces a partial epithelial to mesenchymal transition and
      promotes squamous carcinoma cell invasion and metastasis.
AB  - Evidence shows that Bcl-2 family members play a direct role in the development of
      some human malignancies. However, the mechanism by which Bcl-2 may influence
      tumor cell invasion and metastasis remains unclear. Ectopic overexpression of Bcl
      2 in the human squamous carcinoma cell line HSC-3 enhanced tumorigenicity and
      experimental pulmonary metastasis. Interestingly, Bcl-2-expressing cells showed
      morphologic changes that resembled that of cells with an epithelial-mesenchymal
      transition phenotype. Analysis revealed increased N-cadherin and vimentin
      expression in parallel with attenuated E-cadherin level, along with enhanced
      migration and invasive behavior. Zymography studies confirmed elevated levels of
      matrix metalloproteinase-9 (MMP-9) in media of Bcl-2-expressing cells. siRNA
      mediated suppression of N-cadherin expression not only prevented the enhanced
      invasion but also blocked the increased MMP-9 expression induced by elevated Bcl
      2 expression. Accordingly, pharmacologic inhibition of MMP-9 abrogated the
      increased tumor cell invasion. Furthermore, the Bcl-2-mediated increase in MMP-9
      expression and tumor cell invasion was dependent on fibroblast growth factor
      receptor-1 or extracellular signal-regulated kinase signaling. Collectively, the
      data establish that Bcl-2 overexpression in squamous carcinoma cells induces a
      partial epithelial to mesenchymal transition that promotes not only survival but
      also invasion and metastasis through the N-cadherin/fibroblast growth factor
      receptor/extracellular signal-regulated kinase pathway.

PMID- 20145040
TI  - Targeted cancer stem cell therapies start with proper identification of the
      target.

PMID- 20145041
TI  - Sustained c-Jun-NH2-kinase activity promotes epithelial-mesenchymal transition,
      invasion, and survival of breast cancer cells by regulating extracellular signal
      regulated kinase activation.
AB  - The c-Jun NH(2)-terminus kinase (JNK) mediates stress-induced apoptosis and the
      cytotoxic effect of anticancer therapies. Paradoxically, recent clinical studies
      indicate that elevated JNK activity in human breast cancer is associated with
      poor prognosis. Here, we show that overexpression of a constitutively active JNK
      in human breast cancer cells did not cause apoptosis, but actually induced cell
      migration and invasion, a morphologic change associated with epithelial
      mesenchymal transition (EMT), expression of mesenchymal-specific markers vimentin
      and fibronectin, and activity of activator protein transcription factors.
      Supporting this observation, mouse mammary tumor cells that have undergone EMT
      showed upregulated JNK activity, and the EMT was reversed by JNK inhibition.
      Sustained JNK activity enhanced insulin receptor substrate-2-mediated ERK
      activation, which in turn increased c-Fos expression and activator protein
      activity. In addition, hyperactive JNK attenuated the apoptosis of breast cancer
      cells treated by the chemotherapy drug paclitaxel, which is in contrast to the
      requirement for inducible JNK activity in response to cytotoxic chemotherapy.
      Blockade of extracellular signal-regulated kinase activity diminished hyperactive
      JNK-induced cell invasion and survival. Our data suggest that the role of JNK
      changes when its activity is elevated persistently above the basal levels
      associated with cell apoptosis, and that JNK activation may serve as a marker of
      breast cancer progression and resistance to cytotoxic drugs.

PMID- 20145042
TI  - Myeloid zinc finger 1 induces migration, invasion, and in vivo metastasis through
      Axl gene expression in solid cancer.
AB  - Myeloid zinc finger 1 (MZF1) is a member of the SCAN domain family transcription
      factors that form dimers through their highly conserved SCAN motifs. Silencing of
      MZF1 inhibits cell proliferation, and abnormal expression of MZF1 results in
      cancer development. However, a potential role of MZF1 in metastasis remains
      unclear. Axl is a receptor tyrosine kinase and was first identified as a
      transforming gene in chronic myeloid leukemia. Axl overexpression induces
      proliferation, migration, and invasion and is highly expressed in different human
      cancers. In this study, we show that overexpression of MZF1 induces migration and
      invasion in colorectal (Rko, SW480) and cervical (HeLa) cancer cells. In
      addition, we show that MZF1 binds to the Axl promoter, transactivates promoter
      activity, and enhances Axl-mRNA and protein expression in a dose-dependent
      manner. In vitro, sh-RNA knockdown of Axl reduced MZF1-induced migration and
      invasion in HeLa and Rko cells (P = 0.05). Additionally, Rko cells overexpressing
      MZF1 showed increased tumor formation and liver metastasis in the chicken-embryo
      metastasis assay in vivo. Furthermore, the expression of MZF1 and Axl was
      significantly higher in resected colorectal tumors compared with corresponding
      normal tissues (P = 0.02; P = 0.05), and MZF1 expression was positively
      correlated with Axl gene expression in tumor tissues (P < 0.01). Taken together,
      this is the first study to show that MZF1 induces invasion and in vivo metastasis
      in colorectal and cervical cancer, at least in part by regulating Axl gene
      expression.

PMID- 20145043
TI  - FEN1 functions in long patch base excision repair under conditions of oxidative
      stress in vertebrate cells.
AB  - From in vitro studies, flap endonuclease 1 (FEN1) has been proposed to play a
      role in the long patch (LP) base excision repair (BER) subpathway. Yet the role
      of FEN1 in BER in the context of the living vertebrate cell has not been
      thoroughly explored. In the present study, we cloned a DT40 chicken cell line
      with a deletion in the FEN1 gene and found that these FEN1-deficient cells
      exhibited hypersensitivity to H(2)O(2). This oxidant produces genotoxic lesions
      that are repaired by BER, suggesting that the cells have a deficiency in BER
      affecting survival. In experiments with extracts from the isogenic FEN1 null and
      wild-type cell lines, the LP-BER activity of FEN1 null cells was deficient,
      whereas repair by the single-nucleotide BER subpathway was normal. Other
      consequences of the FEN1 deficiency were also evaluated. These results illustrate
      that FEN1 plays a role in LP-BER in higher eukaryotes, presumably by processing
      the flap-containing intermediates of BER.

PMID- 20145044
TI  - Plasticity of the RNA kink turn structural motif.
AB  - The kink turn (K-turn) is an RNA structural motif found in many biologically
      significant RNAs. While most examples of the K-turn have a similar fold, the
      crystal structure of the Azoarcus group I intron revealed a novel RNA
      conformation, a reverse kink turn bent in the direction opposite that of a
      consensus K-turn. The reverse K-turn is bent toward the major grooves rather than
      the minor grooves of the flanking helices, yet the sequence differs from the K
      turn consensus by only a single nucleotide. Here we demonstrate that the reverse
      bend direction is not solely defined by internal sequence elements, but is
      instead affected by structural elements external to the K-turn. It bends toward
      the major groove under the direction of a tetraloop-tetraloop receptor. The
      ability of one sequence to form two distinct structures demonstrates the inherent
      plasticity of the K-turn sequence. Such plasticity suggests that the K-turn is
      not a primary element in RNA folding, but instead is shaped by other structural
      elements within the RNA or ribonucleoprotein assembly.

PMID- 20145045
TI  - Models to predict changes in serum IGF1 and body composition in response to GH
      replacement therapy in GH-deficient adults.
AB  - OBJECTIVE: Clinical response to GH therapy in GH-deficient (GHD) adults varies
      widely. Good predictors of treatment response are lacking. The aim of the study
      was to develop mathematical models to predict changes in serum IGF1 and body
      composition (BC) in response to GH therapy in GHD adults. DESIGN AND METHODS: One
      hundred and sixty-seven GHD patients (103 men, median age 50 years) were studied
      before and after 12 months of GH treatment. GH dose was tailored according to
      serum IGF1 concentrations. Good responders (GR) and poor responders (PR) to GH
      therapy were defined as patients with a response >60th and <40th percentile
      respectively, for changes in serum IGF1 levels (adjusted for GH cumulative dose)
      and in BC (lean body mass (LBM) and body fat determined using dual-energy X-ray
      absorptiometry). A logistic regression model was used to predict the probability
      of being a GR or PR. RESULTS: In the IGF1 prediction model, men (odds ratio (OR)
      5.62: 95% confidence interval 2.59-12.18) and patients with higher insulin levels
      (OR 1.06: 1.00-1.12) were more likely to be GR. The accuracy of the prediction
      model was 70%. In the BC model, men (OR 10.72: 1.36-84.18) and GHD patients with
      lower LBM (OR 0.82: 0.73-0.92) and greater height (OR 1.23: 1.08-1.40) at
      baseline were more likely to be GR. The accuracy of the prediction model was 80%.
      CONCLUSION: Accurate mathematical models to predict GH responsiveness in GHD
      adults were developed using gender, body height, baseline LBM, and serum insulin
      levels as the major clinical predictors.

PMID- 20145046
TI  - Increased circulating adiponectin levels and decreased leptin/soluble leptin
      receptor ratio throughout puberty in female ballet dancers: association with body
      composition and the delay in puberty.
AB  - INTRODUCTION: Ballet dancers (BDs) have a negative energy balance related to
      physical training that results in alterations in body composition, sexual
      development, and adipokine secretion. Our aims were to study anthropometric
      parameters, body composition, and their relationship with adipokines throughout
      pubertal development. SUBJECTS AND METHODS: We carried out a prospective follow
      up study of 22 female Caucasian BDs (Tanner II stage) followed throughout
      puberty. Nutritional status was determined by measurement of height, weight, and
      body mass index (BMI). We calculated growth velocity, bone maturity, and body
      composition at Tanner stages II, III, and V by dual energy X-ray absorptiometry.
      Circulating leptin, adiponectin, and soluble leptin receptor (sObR) levels were
      determined. RESULTS: BDs presented a delay in skeletal maturation during puberty,
      without affectation of final height. Energy intake was deficient according to
      their physical exercise, and they had a delay of 1 year in the mean age of
      menarche. Leptin levels were decreased, whereas sObR and adiponectin levels were
      increased throughout puberty. The percentage of trunk fat, total fat mass, and
      fat of the extremities was decreased throughout the study period (P<0.01). Lean
      mass was increased in the lower extremities, and bone mineral density was normal.
      CONCLUSION: A negative energy balance together with maintained physical exercise
      induced modifications in body composition in BDs. Changes in leptin and
      adiponectin levels appear to be more related to total fat content than to BMI.
      Furthermore, the onset and delayed progress of puberty may be related with an
      inadequate energy balance due to increased exercise.

PMID- 20145047
TI  - Acromegaly per se does not increase the risk for coronary artery disease.
AB  - CONTEXT: Information about the risk and course of coronary artery disease (CAD)
      in acromegaly is limited. OBJECTIVE: To evaluate CAD risk in acromegalic patients
      at diagnosis and after successful treatment during follow-up. SUBJECTS AND
      METHODS: Twenty-five consecutive patients (age 45.1+/-10.6 years, 15 women) were
      studied at the time of diagnosis, and 19 patients were re-evaluated after 4.6+/
      1.1 years. The European Society of Cardiology (ESC) risk score was calculated,
      and a cardiac computed tomography was performed for detection and quantification
      (Agatston score (AS)) of coronary artery calcium (CACs). Fifty age-, sex-, and
      CAD risk-matched subjects and CAC data from the population-based Heinz Nixdorf
      Recall (HNR) study served as controls. RESULTS: In 21 of the 25 patients, the 10
      year risk of developing CAD according to the ESC risk score was low (<10%) and
      high (>20%) in four patients. The AS was lower than in controls (2.6+/-7.9 vs
      66+/-182; P=0.014) and less patients had a positive CAC (AS>0) (20 vs 48%,
      P=0.024), which in the acromegalic patients was less than expected from the HNR
      study. The AS did not correlate with GH excess or disease duration. In 19
      acromegalic patients, who were in remission and re-evaluated after 4.6+/-1.1
      years, the ESC risk (P=0.102) and the AS (P=0.173) did not change significantly
      and no symptomatic CAD event occurred. CONCLUSION: CAD risk in newly diagnosed
      acromegalic patients was low and remained stable after successful treatment. CAC
      was lower than in controls suggesting that GH excess per se does not carry an
      additional CAD risk.

PMID- 20145048
TI  - Temporal orienting deficit after prefrontal damage.
AB  - The aim of this study was to explore, for the first time in patients, the neural
      bases of temporal orienting of attention as well as the interrelations with two
      other effects of temporal preparation: the foreperiod effect and sequential
      effects. We administered an experimental task to a group of 14 patients with
      prefrontal lesion, a group of 15 control subjects and a group of 7 patients with
      a basal ganglia lesion. In the task, a cue was presented (a short versus long
      line) to inform participants about the time of appearance (early versus late) of
      a target stimulus, and the duration of the cue-target time intervals (400 versus
      1400 ms) was manipulated. In contrast to the control group, patients with right
      prefrontal lesion showed a clear deficit in the temporal orienting effect. The
      foreperiod effect was also affected in the group of patients with prefrontal
      lesion (without lateralization of the deficit), whereas sequential effects were
      preserved. The group of basal ganglia patients did not show deficits in any of
      the effects. These findings support the voluntary and strategic nature of the
      temporal orienting and foreperiod effects, which depend on the prefrontal cortex,
      as well as the more automatic nature of sequential effects, which do not depend
      on either prefrontal cortex or frontobasal circuits.

PMID- 20145049
TI  - Pharmacological prion protein silencing accelerates central nervous system
      autoimmune disease via T cell receptor signalling.
AB  - The primary biological function of the endogenous cellular prion protein has
      remained unclear. We investigated its biological function in the generation of
      cellular immune responses using cellular prion protein gene-specific small
      interfering ribonucleic acid in vivo and in vitro. Our results were confirmed by
      blocking cellular prion protein with monovalent antibodies and by using cellular
      prion protein-deficient and -transgenic mice. In vivo prion protein gene-small
      interfering ribonucleic acid treatment effects were of limited duration,
      restricted to secondary lymphoid organs and resulted in a 70% reduction of
      cellular prion protein expression in leukocytes. Disruption of cellular prion
      protein signalling augmented antigen-specific activation and proliferation, and
      enhanced T cell receptor signalling, resulting in zeta-chain-associated protein
      70 phosphorylation and nuclear factor of activated T cells/activator protein 1
      transcriptional activity. In vivo prion protein gene-small interfering
      ribonucleic acid treatment promoted T cell differentiation towards pro
      inflammatory phenotypes and increased survival of antigen-specific T cells.
      Cellular prion protein silencing with small interfering ribonucleic acid also
      resulted in the worsening of actively induced and adoptively transferred
      experimental autoimmune encephalomyelitis. Finally, treatment of myelin basic
      protein(1-11) T cell receptor transgenic mice with prion protein gene-small
      interfering ribonucleic acid resulted in spontaneous experimental autoimmune
      encephalomyelitis. Thus, central nervous system autoimmune disease was modulated
      at all stages of disease: the generation of the T cell effector response, the
      elicitation of T effector function and the perpetuation of cellular immune
      responses. Our findings indicate that cellular prion protein regulates T cell
      receptor-mediated T cell activation, differentiation and survival. Defects in
      autoimmunity are restricted to the immune system and not the central nervous
      system. Our data identify cellular prion protein as a regulator of cellular
      immunological homoeostasis and suggest cellular prion protein as a novel
      potential target for therapeutic immunomodulation.

PMID- 20145050
TI  - Smoking behaviours, access to cigarettes and relationships with alcohol in 15-
      and 16-year-old schoolchildren.
AB  - BACKGROUND: Adolescent smoking is a significant public health concern in the UK
      and across Europe. This study examines smoking behaviours, methods of accessing
      cigarettes and use of non-commercial (fake, foreign and single) cigarettes across
      a sample of schoolchildren. Relationships with alcohol consumption, deprivation,
      personal income and extra-curricular activities are also explored. METHODS: A
      cross-sectional survey of 9833 15- and 16-year-old schoolchildren in the North
      West of England. RESULTS: Cigarettes were most commonly accessed from off
      licences and newsagents, but pupils also reported non-commercial access through
      friends, family and street sellers/neighbours. A high percentage of smokers had
      bought foreign (57%), fake (28%) and single (54%) cigarettes. Frequent binge
      drinking, not participating in extra-curricular activities, receiving greater
      personal income, and having parents that smoked were significantly associated
      with being a regular and heavier smoker. Frequent binge drinking was also
      significantly associated with buying foreign/fake or single cigarettes. A higher
      percentage of those living in deprived areas were current smokers, although
      deprivation was not an independent predictor of cigarette use. CONCLUSION:
      Strategies that restrict commercial access to cigarettes among adolescents may
      increase their reliance on social methods of access, and use of fake, foreign and
      single cigarettes. Interventions to reduce adolescent smoking must recognize the
      critical role of parents and communities in discouraging smoking and preventing
      social access to cigarettes in children. A joint approach to prevention is
      required that targets children at risk of smoking, heavy alcohol use and
      associated health-damaging behaviours.

PMID- 20145051
TI  - The dangers of heparin flushes.

PMID- 20145052
TI  - International Hippocrates prize for poetry and medicine.

PMID- 20145053
TI  - Survey of major complications of intercostal chest drain insertion in the UK.
AB  - BACKGROUND: Following reports from the National Patient Safety Agency of deaths
      and serious harm from intercostal chest drains (ICD) we conducted a national
      survey among chest physicians of their experience of harm associated with ICD.
      METHODS: A questionnaire was sent to 198 UK chest physicians at 148 acute
      hospital trusts, enquiring about current practice and any adverse incidents
      related to chest drains from 2003 to 2008. RESULTS: 101 of 148 trusts (68%)
      replied. 67 trusts reported at least one major incident involving ICD insertion.
      31 Cases of ICD misplacement were reported with seven deaths. Misplaced drains
      were inserted in liver (10), peritoneal space (6), heart (5), spleen (5),
      subclavian vessels (2), colon (1), oesophagus (1) and inferior vena cava (1). 47
      cases of serious lung or chest wall injuries with eight deaths and six cases of
      ICD placement on the wrong side with two deaths were reported. The guidewire was
      lost in the pleural cavity in three cases. 22 of 101 trusts required written
      patient consent before ICD insertion. 11 trusts had a training policy. 16 trusts
      had patient information literature for this procedure. The seniority of doctors
      permitted to insert ICDs was as follows: 30% any doctor; 27% at least 1 year post
      qualification; 32% at least 2 years, 11% at least 4 years. CONCLUSIONS: 67% of
      responding trusts had encountered major complications of ICD. The survey raised
      concerns about training and consent. The National Patient Safety Agency has made
      recommendations to address these risks which are also addressed in the 2009
      update of the British Thoracic Society Pleural Disease Guideline.

PMID- 20145054
TI  - Does the timing of comorbidity affect colorectal cancer survival? A population
      based study.
AB  - OBJECTIVES: Comorbid conditions in colorectal cancer patients can influence both
      clinical eligibility for treatment and survival. We aimed to evaluate the effect
      of comorbidity on 1 year survival from colorectal cancer, and to assess whether
      this effect varied with the timing of the comorbidity in relation to the cancer
      diagnosis. STUDY DESIGN AND SETTING: A population based cohort of 29,563
      colorectal cancer patients diagnosed between 1997 and 2004 in the North West of
      England was evaluated. The excess hazard of death up to 1 year after diagnosis
      was estimated using deprivation and region specific life tables to adjust for
      background mortality. Results were adjusted for age and stage at diagnosis.
      RESULTS: Comorbid conditions diagnosed during the period 18 to 6 months before
      the diagnosis of colorectal cancer were strongly associated with lower survival
      at 1 year. Stage and age remained the strongest predictors of cancer related
      mortality even after adjustment for comorbidity. CONCLUSIONS: Administrative data
      provide a good estimate of the prevalence of most comorbid conditions but may be
      biased for some comorbid conditions that can be contra-indicators for cancer
      treatment. The time window in which a comorbid condition occurs in relation to
      the cancer diagnosis should be taken into account. Adjustment should be carried
      out, where possible, to provide more robust and clinically appropriate
      comparisons of population based cancer patient survival.

PMID- 20145055
TI  - Diagnostic utility of anti-Ro52 detection in systemic autoimmunity.
AB  - OBJECTIVES: To determine the prevalence and diagnostic utility of monospecific
      anti-Ro52 (defined as an immune response against Ro-52 antigen in the absence of
      reactivity to Ro-60 antigen) reactivity in selected autoimmune diseases. STUDY
      DESIGN: Stored diagnostic non-consecutive serum samples obtained from patients
      with systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS),
      systemic sclerosis, idiopathic inflammatory myopathies (IIM), rheumatoid
      arthritis, primary biliary cirrhosis and mixed essential cryoglobulinaemia were
      analysed by line immunoassay to detect the presence of anti-Ro52 and other
      autoantibodies. RESULTS: Monospecific anti-Ro52 reactivity was found in 51
      (12.7%) of the 402 samples tested. Anti-Ro52 was the most common serological
      marker in patients with IIM (35/147, 23.8%) and co-occurred with anti-Jo1 (10/18,
      55.6%; p=0.02). The prevalence of anti-Ro52 reactivity was significantly more
      than anti-Ro60 reactivity in patients with IIM, systemic sclerosis, primary
      biliary cirrhosis, mixed essential cryoglobulinemia and pSS. The mean signal
      intensity of anti-Ro52 reactivity was significantly higher in pSS than SLE and
      associated with rheumatoid factor positivity. The mean signal intensity of anti
      Ro52 correlated with anti-Ro60 and anti-La in pSS and SLE. CONCLUSIONS:
      Monospecific anti-Ro52 reactivity is not disease specific but may be of
      importance in patients with IIM. Furthermore, as anti-Ro52 reactivity is more
      prevalent than anti-Ro60 reactivity in certain autoimmune conditions, specific
      testing for their distinction in clinical practice is recommended.

PMID- 20145056
TI  - Systemic inflammatory response syndrome in diseases of the skin.
AB  - BACKGROUND: A number of dermatological conditions present with features of
      systemic inflammatory response syndrome (SIRS). This study evaluated the
      incidence and outcome of SIRS in patients with dermatological diseases. STUDY
      DESIGN: Prospective cohort study. RESULTS: Patients admitted to a university
      hospital with a skin disease and fulfilling at least two SIRS criteria were
      included. The primary outcome measure was mortality. Secondary outcomes included
      incidence of multiple organ dysfunction syndrome (MODS), sepsis, severe sepsis
      and shock. Over 14 months, 2765 inpatients with skin related problems were
      examined. These included 721 patients admitted directly to the dermatology ward
      and 2044 patients referred from other departments within the hospital, with
      cutaneous manifestations. The incidence of SIRS in this cohort was 2.4% (n=67).
      The mean (SD) age was 32.6 (19.7) years with a male:female ratio of 1.2:1.
      Cutaneous adverse drug reaction (CADR) was the most common cause of SIRS (35.8%).
      During hospitalisation, 37 patients (55.2%) developed sepsis, 23 (34.4%) MODS, 15
      (22.4%) severe sepsis and 6 (9%) shock. Methicillin sensitive Staphylococcus
      aureus was the most common skin isolate (41.4%) and Enterococcus the most common
      blood isolate. Overall mortality was 15% (10/67). Older age, low albumin, MODS,
      severe sepsis and shock were associated with an increased risk of death (p<0.03).
      Positive blood cultures, liver or lung involvement were also significantly
      associated with increased mortality (p<0.01). CONCLUSION: The incidence of SIRS
      was low in dermatological diseases. In this cohort, CADR was the most common
      cause of SIRS. Patients who developed sepsis or MODS had a poor outcome.

PMID- 20145057
TI  - An audit of the effect of oxygen prescription charts on clinical practice.
AB  - PROBLEM: The need to improve the prescription, administration and monitoring of
      oxygen therapy. DESIGN: An interventional, prospective audit. BACKGROUND AND
      SETTING: Wellington Hospital, a teaching and tertiary referral hospital in New
      Zealand in 2007 and 2008. KEY MEASURES FOR IMPROVEMENT: Demonstration of adequate
      oxygen prescribing, administration and monitoring of oxygen therapy. STRATEGIES
      FOR IMPROVEMENT: The introduction of a new drug chart with a specific oxygen
      prescription section. Targeted educational lectures primarily to medical staff.
      EFFECTS OF CHANGE: 610 and 566 patients were reviewed in the first and second
      audits. After introduction of the new oxygen prescription section on the drug
      chart the proportion of patients whose oxygen therapy was prescribed increased
      from 15/85 (17.6%) to 39/98 (39.8%), relative risk 2.3 (95% CI 1.3 to 3.9). The
      proportion with adequate oxygen prescription, with documentation of device, flow
      rate or inspired oxygen concentration, and the target oxygen saturation increased
      from 5/85 (5.9%) to 36/98 (36.7%), relative risk 6.2 (95% CI 2.5 to 15.0).
      Introduction of the new charts was not associated with changes in clinical
      practice in terms of assessment of oxygen saturations on room air and
      commencement if < or = 92%, or the titration of oxygen therapy in response to
      oxygen saturations < or = 92%. LESSONS LEARNT: An oxygen prescription section on
      hospital drug charts improved the prescription of oxygen but did not improve
      clinical practice. Additional strategies are required to improve the
      administration of oxygen therapy in hospitals.

PMID- 20145058
TI  - Early dietary exposures and feeding practices: role in pathogenesis and
      prevention of allergic disease?
AB  - Immune dysregulation has become a hallmark of the modern era. This has led to an
      epidemic of disease states that result from failed immune surveillance and
      inappropriate or maladaptive immune responses to self-antigens (autoimmunity) and
      environmental antigens (allergy). Although environmental change is clearly
      implicated, the specific causes are still unconfirmed. Any hope to reverse such
      immune dysfunction must be based on a clearer understanding of the causal
      pathways and the environmental factors that may be driving the concerning surge
      in disease rates. This review explores the role of modern dietary changes that,
      through their known documented immune effects, may play a role in either
      promoting or preventing disease. Food allergen avoidance has been largely
      unsuccessful, and most expert bodies no longer recommend delayed complementary
      feeding or the avoidance of any specific allergenic foods, unless symptoms
      develop and allergy is confirmed. Rather, focus has shifted to other factors that
      may influence the ability to develop immune tolerance. There is now evidence that
      specific nutrients, such as folate, have the capacity to promote an allergic
      phenotype by epigenetically altering gene expression during early development. A
      number of other dietary factors including n-3 polyunsaturated fatty acids,
      oligosaccharides, probiotics, vitamin D, retinoic acid and other antioxidants may
      also clearly influence immune function and immune development. This review
      summarises the current evidence, recommendations and future directions in the
      context of allergy, with the aim of highlighting the need to further investigate
      the role of diet and nutrition in disease pathogenesis and prevention.

PMID- 20145059
TI  - Management of pregnancy in women with acquired and congenital heart disease.
AB  - Heart disease is the leading cause of maternal mortality in the UK. Deaths from
      acquired conditions such as ischaemic heart disease are increasing and often
      occur in patients with no history of heart disease, thus emphasising the need for
      vigilance for risk factors in women of childbearing age. All women with known
      heart disease should have pre-pregnancy counselling to assess for maternal and
      fetal risk. Women deemed to be at moderate or high risk should be under the care
      of a specialist antenatal team with experience of managing women with heart
      disease in pregnancy. Conditions that are considered particularly high risk
      (mortality >10%) include Marfan syndrome with dilated aortic root, severe left
      heart obstructive lesions, pulmonary hypertension, and severe left ventricular
      dysfunction. This article reviews the management of women with heart disease
      during pregnancy, labour and in the puerperium.

PMID- 20145060
TI  - Endobronchial ultrasound guided transbronchial needle aspiration.
AB  - Staging for non-small cell lung cancer (NSCLC) requires accurate assessment of
      the mediastinal lymph nodes which determines treatment and outcome. As
      radiological staging is limited by its specificity and sensitivity, it is
      necessary to sample the mediastinal nodes. Traditionally, mediastinoscopy has
      been used for evaluation of the mediastinum especially when radical treatment is
      contemplated, although conventional transbronchial needle aspiration (TBNA) has
      also been used in other situations for staging and diagnostic purposes.
      Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA)
      offers a minimally invasive alternative to mediastinoscopy with additional access
      to the hilar nodes, a better safety profile, and it removes the costs and hazards
      of theatre time and general anaesthesia with comparable sensitivity, although the
      negative predictive value of mediastinoscopy (and sample size) is greater. EBUS
      TBNA also obtains larger samples than conventional TBNA, has superior performance
      and theoretically is safer, allowing real-time sampling under direct vision. It
      can also have predictive value both in sonographic appearance of the nodes and
      histological characteristics. EBUS-TBNA is therefore indicated for NSCLC staging,
      diagnosis of lung cancer when there is no endobronchial lesion, and diagnosis of
      both benign (especially tuberculosis and sarcoidosis) and malignant mediastinal
      lesions. The procedure is different than for flexible bronchoscopy, takes longer,
      and requires more training. EBUS-TBNA is more expensive than conventional TBNA
      but can save costs by reducing the number of more costly mediastinoscopies.
      Revenue based tariff systems have been slow to reflect the innovation of
      techniques such as EBUS-TBNA. In the future, endobronchial ultrasound may have
      applications in airways disease and pulmonary vascular disease.

PMID- 20145061
TI  - Role of implantable cardioverter defibrillators in non-ischaemic dilated
      cardiomyopathy.
AB  - Patients with non-ischaemic dilated cardiomyopathy (NICM) are at significant risk
      of sudden cardiac death. Multiple randomised trials have shown that implantable
      cardioverter defibrillators (ICDs) reduce mortality in high-risk patients with
      NICM. However, despite this, the National Institute for Health and Clinical
      Excellence specifically excluded patients with NICM from its updated guidance
      concerning ICD use. This lack of guidance poses clear problems for both
      clinicians managing patients with NICM and those who commission healthcare
      services. This review aims to help guide clinicians in this difficult, high-cost
      and high-risk area.

PMID- 20145062
TI  - Doctors' views of attitudes towards peer medical error.
AB  - BACKGROUND: This study aims at evaluating doctors' attitudes towards handling
      medical errors made by their peers. MATERIALS: This cross-sectional questionnaire
      survey was conducted between April and July 2006 and targeted general
      practitioners attending continuing medical education programmes in Tehran. A
      total of 474 doctors were approached, 400 of whom completed the questionnaire.
      The questionnaire contained a clinical vignette with three hypothetical patient
      outcomes: near-miss, leading to harm, and leading to death. The participants were
      asked how they would deal with each case. They were also asked how they would
      prefer their peers to react when they themselves made a medical error. RESULTS:
      The most common attitude toward peers' medical errors was reporting it to the
      original doctor and asking them to disclose it to the patient (near-miss: 63.0%;
      95% CI 58% to 68%; leading to harm: 70.0%; 95% CI 65.4% to 74.6%; and leading to
      death: 62.5%; 95% CI 57.5% to 67.5%). In most cases, doctors expected their peers
      to report their medical errors to them (92.7%; 95% CI 89.7% to 93.0). About 67%
      of the participating doctors had encountered a peer's medical error in the past 6
      months, although 90% of them had received no or very little training in dealing
      with this issue. DISCUSSION: The most acceptable approach to dealing with a
      peer's medical error is to report it to the responsible doctor and encourage them
      to disclose it to the patient.

PMID- 20145064
TI  - A typology of dental students according to their experience of stress: a
      qualitative study.
AB  - Dental students often report high levels of stress. Even though many studies have
      been conducted on this issue, we still lack a global understanding of how dental
      students experience and deal with stress, making it difficult for dental
      educators to improve this situation. Consequently, our study aimed to understand
      in a comprehensive manner how dental students experience stress. We conducted a
      qualitative research study based on in-depth one-on-one interviews with twelve
      recent graduates from a Canadian dental school. The interviews were recorded and
      transcribed verbatim. We then analyzed the transcripts in a process that included
      coding, displaying, and interpreting data. We identified three types of students:
      highly stressed, moderately stressed, and relaxed students. Relaxed students
      reported very low levels of stress, which they dealt with by using good coping
      skills. Moderately stressed students were more affected, but they considered
      stress as acceptable and even helpful as it pushed them to perform better and
      succeed. Finally, highly stressed students showed alarming levels of stress and
      described it as "crippling" and "unmanageable." They felt helpless and explained
      that stress had negative repercussions for their physical and mental health as
      well as their social life. They related stress to fear of failing, heavy
      workload, and difficulties in dealing with transitions in the curriculum and
      sometimes to difficult relationships with the academic staff. They dealt with
      stress by using poor coping skills. It is crucial to help highly stressed
      students by both reducing their sources of stress and helping them develop
      appropriate coping strategies.

PMID- 20145065
TI  - Clinical experience of residents with RPD treatment in U.S. graduate
      prosthodontics programs.
AB  - This cross-sectional study was conducted to quantify the clinical experience of
      prosthodontic residents with cast metal removable partial denture (RPD) treatment
      based on their year of training, geographic location of the program, and nature
      of the program. A web-based survey consisting of five questions was e-mailed to
      program directors from forty-two programs across the United States. A 62 percent
      response rate was obtained (26/42). Thirteen of the programs (50 percent of
      respondents) stipulated a specific number of RPDs to be done prior to completion
      of the program. Clinical experience of residents varied vastly based on year of
      training, geographic location of the program, and nature of the program.
      Prosthodontic residents from southern states, university-based programs, and
      public school programs had more clinical experience than residents from other
      programs. The average clinical experience for a prosthodontic resident during
      three years of training was eight traditional RPDs and two implant-supported
      RPDs. This is the first study done exploring this topic and provides baseline
      information on residents' clinical experience in RPD treatment. Future studies
      will determine educational trends and reassess this portion of the curriculum in
      graduate prosthodontics.

PMID- 20145066
TI  - Evaluation of a 3-D interactive tooth atlas by dental students in dental anatomy
      and endodontics courses.
AB  - Advances in information and communication technology continually offer
      innovations to assist faculty in their efforts to help students learn new
      information or develop new skills. However, faculty members are often hesitant to
      incorporate these innovations into their courses out of fear that these new
      methods may not provide the anticipated outcomes. Hence, students are often the
      subjects of educational trials to evaluate curriculum innovations by comparing a
      new teaching/learning method to traditional lecture-based instruction. The most
      typical finding is that students can learn equally well by either method.
      However, two questions that have not been studied extensively in dental education
      are whether dental students will actually use computer-based educational
      resources made available to them and whether students perceive these materials to
      provide a value-added learning experience. Accordingly, the goals of this study
      were to determine whether first-year dental students (D1), second-year dental
      students (D2), and third-year dental students (D3) would 1) use an interactive
      tooth atlas, available on a DVD, as a study aid and 2) perceive that the atlas
      provided sufficient value-added benefit for their dental anatomy (D1),
      preclinical laboratory endodontics (D2), and clinical endodontics (D3) courses to
      recommend adding it to their school's comprehensive electronic resources. A low
      percentage of the students (14 percent; 40/289) voluntarily downloaded the atlas
      from a DVD to their laptops prior to the addition of incentives in the form of
      atlas-related examination questions. Even after incentives were added, only 43
      percent of the students (126/289) downloaded the DVD. After using the atlas,
      students responded to the statement "Using the 3D Interactive Tooth Atlas was
      beneficial for me" on a 0 to 10 scale with 0 representing strongly disagree, 5
      representing unsure, and 10 representing strongly agree. The mean rankings were
      5.34 for D1s, 6.79 for D2s, and 7.28 for D3s. Students also responded to the
      statement "The atlas should be added to our school's VitalBook" (digital library
      of curriculum materials). The mean rankings for this statement, using the same 0
      10 scale, were 5.15 for the D1s, 6.63 for the D2s, and 7.26 for the D3s. Based
      upon these findings, the course directors decided not to add this atlas to the
      students' electronic resources.

PMID- 20145067
TI  - Senior dental students' experience with Cariogram in a pediatric dentistry
      clinic.
AB  - The study objective was to assess predoctoral dental students' experience with a
      caries risk assessment computer program in the pediatric dentistry clinic at
      Marquette University School of Dentistry. In 2005, spring semester sophomore
      dental students (class of 2008) were introduced to the caries risk assessment
      computer program "Cariogram." The students received a fifty-minute lecture on
      caries risk assessment and a demonstration on how to use Cariogram in the clinic.
      After two years of clinical exposure to Cariogram, sixty-six out of eighty senior
      dental students completed an anonymous eleven-item questionnaire on their
      experience with the tool. Each item on the questionnaire was scored on a five
      point Likert scale with the exception of two questions. Full- and part-time
      faculty members in the pediatric dentistry clinic were involved in teaching and
      supervising students in the use of Cariogram for caries risk assessment after
      their training and calibration. Forty-five percent of the students who
      participated in the study agreed that Cariogram was easy to understand, and 18
      percent disagreed. Thirty-six percent felt that it was easy to apply, and 25
      percent reported that it was useful in determining caries preventive procedures.
      The students reported that 60 percent of full-time and 33 percent of part-time
      faculty were knowledgeable about Cariogram use. A majority of the students felt
      that Cariogram was not easy to understand, and eighty-two percent of them
      reported that they would not be using Cariogram in their private offices. Future
      studies should explore reasons why students do not feel inclined to use Cariogram
      as a caries risk assessment tool in their private practices even after being
      exposed to the tool in dental school.

PMID- 20145068
TI  - A competency-based framework for training in advanced dental education:
      experience in a community-based dental partnership program.
AB  - While goals and objectives are useful to assess programmatic outcomes, they are
      not able to evaluate individual trainees' performance and/or corrective actions
      needed to improve performance. As a result, competency-based evaluation is
      increasingly being used to assess trainee performance at both the doctoral and
      postdoctoral levels. However, the translation of broadly stated competency
      statements into evaluable action statements continues to pose a challenge,
      especially in nontechnical domains such as the assessment and integration of
      cultural and sociodemographic variables in the development and execution of
      treatment plans. This article describes a process used to develop a competency
      based framework that includes specific evaluable action statements to assess the
      performance of Advanced Education in General Dentistry (AEGD) residents providing
      dental care services to medically compromised patients in a community-based
      partnership program. Although the resultant framework may not itself be
      generalizable across training programs, the process described to develop the
      framework can be used by those individuals involved in evaluating students and/or
      residents in training programs.

PMID- 20145069
TI  - Effect of tobacco counseling by dental students on patient quitting rate.
AB  - Tobacco use has widespread, devastating effects on the body, including the oral
      cavity. Today's dental professional must be trained to counsel patients on
      tobacco cessation, but dental health professionals and students do not feel
      confident in their counseling abilities. The University at Buffalo School of
      Dental Medicine (SDM) established the Tobacco Counseling Cessation Protocol
      (TCCP), which was implemented in the dental curriculum, and dental students were
      trained in its use. The goal of this project was to assess the effectiveness of
      the TCCP by surveying both patients and dental students. Students and patients
      were contacted to determine the effect of the TCCP on the quitting rate. Third-
      and fourth-year dental students were surveyed through the school e-mail system
      and asked to report on their tobacco cessation counseling practices. Patients who
      received TCCP received follow-up telephone calls to obtain their input on the
      program and also to determine if they had quit. According to the follow-up
      survey, 14 percent of patients reduced the number of cigarettes smoked per day,
      and 22 percent quit entirely. Fifty-one percent of those who received the TCCP
      made a commitment to quit at the time of the intervention; 32 percent of those
      receiving the TCCP were still smoke-free at six months, but 19 percent had
      returned to smoking. If predoctoral students receive appropriate training, they
      can be effective in motivating patients to quit smoking. Dental students are
      generally receptive to the educational material on tobacco use and smoking
      cessation counseling, yet only half report routinely implementing the TCCP. More
      needs to be done to incorporate tobacco cessation counseling into routine dental
      care. The culture of dentistry must be changed to view tobacco use as a dental
      problem.

PMID- 20145075
TI  - NME1 at the human maternal-fetal interface downregulates titin expression and
      invasiveness of trophoblast cells via MAPK pathway in early pregnancy.
AB  - Nometastatic gene 23-H1 (NME1, also known as nm23-H1) is a wide-spectrum tumor
      metastasis suppressor gene that plays an important role in suppressing the
      invasion and metastasis of tumor cells. It has been demonstrated that NME1 is
      also expressed in human first-trimester placenta, but its function at maternal
      fetal interface is not clear. The present study aimed to elucidate the biological
      function of NME1 at the maternal-fetal interface, especially on invasion of the
      human extravillous cytotrophoblasts (EVCTs). NME1 has been identified in both
      human trophoblast cells and decidual stromal cells (DSCs) in early pregnancy. We
      have proved that NME1 silencing in vitro increases the titin protein translation
      in the invasive EVCTs. Moreover, NME1 can inactivate the phospho-extracellular
      signal-regulated kinase 1/2 (P-ERK1/2) in trophoblasts in a time-dependent
      manner, and U0126, an inhibitor of MAPK/ERK, can inhibit partly the enhanced
      invasiveness and titin expression in trophoblasts induced by NME1 silencing.
      Interestingly, the expression of NME1 in either villi or decidua is higher
      significantly in miscarriage than that of the normal early pregnancy. These
      findings first reveal that the NME1 expressed in trophoblasts and DSCs controls
      the inappropriate invasion of human first-trimester trophoblast cells via
      MAPK/ERK1/2 signal pathway, and the overexpression of NME1 at maternal-fetal
      interface leads to pregnancy wastage.

PMID- 20145076
TI  - Crystal structure of the narrow-spectrum OXA-46 class D beta-lactamase:
      relationship between active-site lysine carbamylation and inhibition by
      polycarboxylates.
AB  - Class D beta-lactamases represent a heterogeneous group of active-site serine
      beta-lactamases that show an extraordinary panel of functional features and
      substrate profiles, thus representing relevant models for biochemical and
      structural studies. OXA-46 is a narrow-spectrum enzyme belonging to the OXA-2
      subgroup which was found in a Pseudomonas aeruginosa clinical isolate from
      northern Italy. In this work, we obtained the three-dimensional structure of OXA
      46, which shows the overall fold of active serine beta-lactamases and a dimeric
      quaternary structure. Significant differences with currently available structures
      of class D beta-lactamases were found in the loops located close to the active
      site, which differ in length and conformation. Interestingly, the three subunits
      present in the asymmetric unit showed some structural heterogeneity, only one of
      which presented a carbamylated lysine recognized as an important functional
      feature of class D enzymes. The carbamylation state of residue Lys75 appeared to
      be associated with different shapes and dimensions of the active site. Moreover,
      a tartrate molecule from the crystallization buffer was found in the active site
      of the noncarbamylated subunits, which interacts with catalytically relevant
      residues. The OXA-46 crystal asymmetric units thus interestingly present the
      structures of the free carbamylated active site and of the ligand-bound
      uncarbamylated active site, offering the structural basis for investigating the
      potential of new scaffolds of beta-lactamase inhibitors.

PMID- 20145077
TI  - Correlation between in vitro activity of posaconazole and in vivo efficacy
      against Rhizopus oryzae infection in mice.
AB  - We have evaluated the in vitro activity of posaconazole (PSC) against 50 clinical
      strains of Rhizopus oryzae using a broth microdilution method, the Neo-Sensitabs
      tablet diffusion method, and minimal fungicidal concentration (MFC)
      determination. In general, PSC showed low MICs against this fungus, and the MICs
      correlated with the inhibition zone diameters. Most of the MFCs, however, were
      from 1 to 4 dilutions higher than their corresponding MICs. We then investigated
      the efficacies of several different doses of PSC in a murine model. All
      treatments began 24 h after challenge and lasted for 7 days. The drug was
      administered twice a day to mice infected with three strains that showed
      intermediate PSC susceptibility (MIC = 2 microg/ml) and three PSC-susceptible
      strains (MIC = 0.25 microg/ml). A dose of 10 mg/kg of body weight was
      ineffective, while doses of 20 and 30 mg/kg prolonged the survival of the mice.
      The 50 strains tested were segregated into two groups on the basis of the in
      vitro data. For the group with the most strains (85%), the strains had low PSC
      MICs, mice infected with the strains showed higher rates of survival (30 to 40%),
      and PSC was able to reduce the fungal load in the kidney and less regularly in
      the brain. For the second group (15% of the strains), the strains had
      intermediate PSC MICs, mice infected with the strains had lower survival rates
      (10 to 20%), and PSC treatment resulted in variable and no reductions in the
      fungal loads in the kidneys and brains, respectively.

PMID- 20145078
TI  - Cutaneous model of invasive aspergillosis.
AB  - Cutaneous models have proven useful in studies of the pathogenesis and treatment
      of Gram-positive bacterial infections. Because cutaneous invasive aspergillosis
      (IA) occurs in the clinical setting, we sought to develop a nonlethal murine
      cutaneous model of IA. We induced cutaneous IA in cyclophosphamide-treated nude
      BALB/c mice by subcutaneous injection of Aspergillus fumigatus conidia. Skin
      lesion areas correlated well with tissue fungal burdens, allowing dynamic visual
      monitoring of cutaneous infections. The cutaneous model accurately reflected
      alterations in A. fumigatus pathogenicity resulting from deletions of recognized
      virulence genes (pabaA, sidA, and pksP). Moreover, analysis of the roles of
      conidial and mycelial catalases revealed that the former is required for the
      initiation of cutaneous aspergillosis, whereas the latter contributes to its
      propagation. Finally, posaconazole treatment reduced skin lesion areas relative
      to those of untreated and fluconazole-treated controls. This novel cutaneous
      model system should be applicable to comparative studies of the pathogenesis,
      treatment, and tissue specificity of IA.

PMID- 20145079
TI  - Occurrence of ST23 complex phylogroup A Escherichia coli isolates producing
      extended-spectrum AmpC beta-lactamase in a French hospital.
AB  - Extended-spectrum AmpC beta-lactamase (ESAC) Escherichia coli producers were
      investigated over a 5-year period. Eleven isolates presenting a strong ampC
      promoter and different strategic AmpC mutations, including two newly described
      modifications (A292V and an L-A-A insertion at 295), were characterized. All the
      isolates belonged to phylogenetic group A and to the ST23 complex.

PMID- 20145080
TI  - Changes in the proteome of Candida albicans in response to azole, polyene, and
      echinocandin antifungal agents.
AB  - The yeast Candida albicans is an opportunistic human fungal pathogen and the
      cause of superficial and systemic infections in immunocompromised patients. The
      classes of antifungal agents most commonly used to treat Candida infections are
      the azoles, polyenes, and echinocandins. In the present study, we identified
      changes in C. albicans protein abundance using two-dimensional polyacrylamide gel
      electrophoresis and matrix-assisted laser desorption ionization-time of flight
      mass spectroscopy following exposure to representatives of the azole
      (ketoconazole), polyene (amphotericin B), and echinocandin (caspofungin)
      antifungals in an effort to elucidate the adaptive responses to these classes of
      antifungal agents. We identified 39 proteins whose abundance changed in response
      to ketoconazole exposure. Some of these proteins are involved in ergosterol
      biosynthesis and are associated with azole resistance. Exposure to amphotericin B
      altered the abundance of 43 proteins, including those associated with oxidative
      stress and osmotic tolerance. We identified 50 proteins whose abundance changed
      after exposure to caspofungin, including enzymes involved in cell wall
      biosynthesis and integrity, as well as the regulator of beta-1,3-glucan synthase
      activity, Rho1p. Exposure to caspofungin also increased the abundance of the
      proteins involved in oxidative and osmotic stress. The common adaptive responses
      shared by all three antifungal agents included proteins involved in carbohydrate
      metabolism. Some of these antifungal-responsive proteins may represent potential
      targets for the development of novel therapeutics that could enhance the
      antifungal activities of these drugs.

PMID- 20145081
TI  - Pharmacokinetic-pharmacodynamic assessment of faropenem in a lethal murine
      Bacillus anthracis inhalation postexposure prophylaxis model.
AB  - There are few options for prophylaxis after exposure to Bacillus anthracis,
      especially in children and women of childbearing potential. Faropenem is a beta
      lactam in the penem subclass that is being developed as an oral prodrug,
      faropenem medoxomil, for the treatment of respiratory tract infections. Faropenem
      was shown to have in vitro activity against B. anthracis strains that variably
      express the bla1 beta-lactamase (MIC range, <or=0.06 to 1 microg/ml). In this
      study we evaluated the pharmacokinetic-pharmacodynamic (PK-PD) relationships
      between the plasma faropenem free-drug (f) concentrations and efficacy against B.
      anthracis in a murine postexposure prophylaxis inhalation model. The plasma PKs
      and PKs-PDs of faropenem were evaluated in BALB/c mice following the
      intraperitoneal (i.p.) administration of doses ranging from 2.5 to 160 mg/kg of
      body weight. For the evaluation of efficacy, mice received by inhalation aerosol
      doses of B. anthracis (Ames strain; faropenem MIC, 0.06 microg/ml) at 100 times
      the 50% lethal dose. The faropenem dosing regimens (10, 20, 40, and 80 mg/kg/day)
      were administered i.p. at 24 h postchallenge at 4-, 6-, and 12-h intervals for 14
      days. The sigmoid maximum-threshold-of-efficacy (E(max)) model fit the survival
      data, in which the free-drug area under the concentration-time curve (fAUC)/MIC
      ratio, the maximum concentration of free drug in plasma (fC(max))/MIC ratio, and
      the cumulative percentage of a 24-h period that the free-drug concentration
      exceeds the MIC under steady-state pharmacokinetic conditions (f %T(MIC)) were
      each evaluated. Assessment of f %T(MIC) demonstrated the strongest correlation
      with survival (R(2) = 0.967) compared to the correlations achieved by assessment
      of fAUC/MIC or fC(max)/MIC, for which minimal correlations were observed. The 50%
      effective dose (ED(50)), ED(90), and ED(99) corresponded to f %T(MIC) values of
      10.6, 13.4, and 16.4%, respectively, and E(max) was 89.3%. Overall, faropenem
      demonstrated a high level of activity against B. anthracis in the murine
      postexposure prophylaxis inhalation model.

PMID- 20145082
TI  - Fluoroquinolone resistance in Streptococcus dysgalactiae subsp. equisimilis and
      evidence for a shared global gene pool with Streptococcus pyogenes.
AB  - Quinolone resistance is an emerging problem in Streptococcus pyogenes, and
      recombination with Streptococcus dysgalactiae DNA has been implicated as a
      frequent mechanism leading to resistance. We have characterized a collection of
      S. dysgalactiae subsp. equisimilis isolates responsible for infections in humans
      (n = 314) and found a high proportion of levofloxacin-resistant isolates (12%).
      Resistance was associated with multiple emm types and genetic lineages, as
      determined by pulsed-field gel electrophoretic profiling. Since we could not find
      evidence for a role of efflux pumps in resistance, we sequenced the quinolone
      resistance-determining regions of the gyrA and parC genes of representative
      resistant and susceptible isolates. We found much greater diversity among the
      parC genes (19 alleles) than among the gyrA genes (5 alleles). While single
      mutations in either GyrA or ParC were sufficient to raise the MIC so that the
      strains were classified as intermediately resistant, higher-level resistance was
      associated with mutations in both GyrA and ParC. Evidence for recombination with
      S. pyogenes DNA was found in some parC alleles, but this was not exclusively
      associated with resistance. Our data support the existence of a common reservoir
      of genes conferring quinolone resistance shared between S. dysgalactiae subsp.
      equisimilis and S. pyogenes, while no recombination with the animal pathogen S.
      dysgalactiae subsp. dysgalactiae could be found.

PMID- 20145083
TI  - In vitro fungicidal activities of echinocandins against Candida metapsilosis, C.
      orthopsilosis, and C. parapsilosis evaluated by time-kill studies.
AB  - Anidulafungin, micafungin, and caspofungin in vitro activities against Candida
      metapsilosis, C. orthopsilosis, and C. parapsilosis were evaluated by MICs and
      time-kill methods. All echinocandins showed lower MICs (mean MICs, 0.05 to 0.71
      mg/liter) and the highest killing rates (-0.06 to -0.05 CFU/ml/h) for C.
      metapsilosis and C. orthopsilosis rather than for C. parapsilosis (mean MICs,
      0.59 to 1.68 mg/liter). Micafungin and anidulafungin killing rates were greater
      than those determined for caspofungin. None of the echinocandins had fungicidal
      activity against C. parapsilosis.

PMID- 20145084
TI  - Novel FKS mutations associated with echinocandin resistance in Candida species.
AB  - We studied three clinical isolates of Candida spp. (one C. tropicalis isolate and
      two C. glabrata isolates) from patients with invasive candidiasis. The first
      isolate emerged during echinocandin treatment, while the others emerged after the
      same treatment. These strains harbored an amino acid substitution in Fksp never
      linked before with reduced echinocandin susceptibility in C. tropicalis or in C.
      glabrata. The molecular mechanism of reduced susceptibility was confirmed using a
      1,3-beta-D-glucan synthase inhibition assay.

PMID- 20145085
TI  - PER-6, an extended-spectrum beta-lactamase from Aeromonas allosaccharophila.
AB  - An Aeromonas allosaccharophila environmental isolate recovered from the Seine
      River (Paris, France) produced a novel extended-spectrum beta-lactamase, PER-6,
      that shared 92% amino acid identity with the closest ss-lactamase, PER-2. The
      kinetic properties of PER-6 showed a slightly increased affinity for carbapenems.
      The bla(PER-6) gene was chromosomally located and bracketed by non-transposon
      related structures.

PMID- 20145086
TI  - Dinitroaniline activity in Toxoplasma gondii expressing wild-type or mutant alpha
      tubulin.
AB  - The human parasite Toxoplasma gondii is sensitive to dinitroaniline compounds
      which selectively disrupt microtubules in diverse protozoa but which have no
      detectable effect on vertebrate host cell microtubules or other functions.
      Replication of wild-type T. gondii is inhibited by 0.5 to 2.5 microM oryzalin,
      but mutant parasites harboring amino acid substitutions in the predicted
      dinitroaniline binding site confer resistance up to 40 microM oryzalin. However,
      the precise interaction between dinitroanilines and the binding site in alpha
      tubulin remains unclear. We have investigated the activity of 12 dinitroanilines
      and the related compound amiprophos methyl on wild-type and dinitroaniline
      resistant parasite lines that contain proposed binding site mutations. These data
      indicate that dinitramine is the most effective dinitroaniline to inhibit
      Toxoplasma growth in wild-type parasites and most resistant lines. Dinitramine
      has an amine group at the meta position not present in any of the other
      dinitroanilines tested here that is predicted to form hydrogen bonds with
      residues Arg2 and Gln133 according to docking data. Remarkably, although the
      binding site mutation Ile235Val confers increased resistance to most
      dinitroanilines, it confers increased sensitivity to GB-II-5, a compound
      optimized for activity against kinetoplastid tubulin. Kinetoplastid parasites
      have a valine at position 235 of alpha-tubulin, whereas apicomplexan parasites
      have an isoleucine at this site. We suggest that this heterogeneity in binding
      site environment influences relative dinitroaniline sensitivity in distinct
      protozoan lineages and hypothesize that a mutation that makes the apicomplexan
      dinitroaniline binding site more like the kinetoplastid site increases
      sensitivity to a dinitroaniline optimized for activity in the latter parasites.

PMID- 20145087
TI  - pfmdr1 amplification and fixation of pfcrt chloroquine resistance alleles in
      Plasmodium falciparum in Venezuela.
AB  - Molecular tools are valuable for determining evolutionary history and the
      prevalence of drug-resistant malaria parasites. These tools have helped to
      predict decreased sensitivity to antimalarials and fixation of multidrug
      resistance genotypes in some regions. In order to assess how historical drug
      policies impacted Plasmodium falciparum in Venezuela, we examined molecular
      changes in genes associated with drug resistance. We examined pfmdr1 and pfcrt in
      samples from Sifontes, Venezuela, and integrated our findings with earlier work
      describing dhfr and dhps in these samples. We characterized pfmdr1 genotypes and
      copy number variation, pfcrt genotypes, and proximal microsatellites in 93
      samples originating from surveillance from 2003 to 2004. Multicopy pfmdr1 was
      found in 12% of the samples. Two pfmdr1 alleles, Y184F/N1042D/D1246Y (37%) and
      Y184F/S1034C/N1042D/D1246Y (63%), were found. These alleles share ancestry, and
      no evidence of strong selective pressure on mutations was found. pfcrt
      chloroquine resistance alleles are fixed with two alleles: S(tct)VMNT (91%) and
      S(agt)VMNT (9%). These alleles are associated with strong selection. There was
      also an association between pfcrt, pfmdr1, dhfr, and dhps genotypes/haplotypes.
      Duplication of pfmdr1 suggests a potential shift in mefloquine sensitivity in
      this region, which warrants further study. A bottleneck occurred in P. falciparum
      in Sifontes, Venezuela, and multidrug resistance genotypes are present. This
      population could be targeted for malaria elimination programs to prevent the
      possible spread of multidrug-resistant parasites.

PMID- 20145088
TI  - Antistaphylococcal activity of ACHN-490 tested alone and in combination with
      other agents by time-kill assay.
AB  - Synergy time-kill studies of 47 methicillin-resistant Staphylococcus aureus
      strains with differing resistance phenotypes showed that combinations of
      subinhibitory concentrations of ACHN-490 and daptomycin yielded synergy against
      43/47 strains at 24 h, while the combination was indifferent against the
      remaining 4 strains. ACHN-490 and ceftobiprole showed synergy in 17/47 strains
      tested at 24 h, while 6/47 strains showed synergy for subinhibitory combinations
      of ACHN-490 and linezolid.

PMID- 20145089
TI  - Mutant APH(2'')-IIa enzymes with increased activity against amikacin and
      isepamicin.
AB  - Directed evolution by random PCR mutagenesis of the gene for the aminoglycoside
      2''-IIa phosphotransferase generated R92H/D268N and N196D/D268N mutant enzymes,
      resulting in elevated levels of resistance to amikacin and isepamicin but not to
      other aminoglycoside antibiotics. Increases in the activities of the mutant
      phosphotransferases for isepamicin are the result of decreases in K(m) values,
      while improved catalytic efficiency for amikacin is the result of both a decrease
      in K(m) values and an increase in turnover of the antibiotic. Enzymes with R92H,
      D268N, and D268N single amino acid substitutions did not result in elevated MICs
      for aminoglycosides.

PMID- 20145090
TI  - Eligibility for corneal donation within the hospice population.

PMID- 20145091
TI  - Incidence of sudden, unexpected death in a specialist palliative care inpatient
      setting.

PMID- 20145092
TI  - Time to get it right: are preferences for place of death more stable than we
      think?

PMID- 20145093
TI  - Functional characterization of an extended binding component of the actin-ADP
      ribosylating C2 toxin detected in Clostridium botulinum strain (C) 2300.
AB  - Clostridium botulinum C2 toxin consists of the binding component C2II and the
      enzyme component C2I, which ADP-ribosylates G-actin of eukaryotic cells. Trypsin
      activated C2II (C2IIa) forms heptamers that mediate cell binding and
      translocation of C2I from acidic endosomes into the cytosol of target cells. By
      genome sequencing of C. botulinum strain (C) 2300, we found that C2II from this
      strain carries a C-terminal extension of 129 amino acids, unlike its homologous
      counterparts from strains (C) 203U28, (C) 468, and (D) 1873. This extension shows
      a high similarity to the C-terminal receptor-binding domain of C2II and is
      presumably the result of a duplication of this domain. The C2II extension
      facilitates the binding to cell surface receptors, which leads to an increased
      intoxication efficiency compared to that of C2II proteins from other C. botulinum
      strains.

PMID- 20145094
TI  - Stressor exposure disrupts commensal microbial populations in the intestines and
      leads to increased colonization by Citrobacter rodentium.
AB  - The gastrointestinal tract is colonized by an enormous array of microbes that are
      known to have many beneficial effects on the host. Previous studies have
      indicated that stressor exposure can disrupt the stability of the intestinal
      microbiota, but the extent of these changes, as well as the effects on enteric
      infection, has not been well characterized. In order to examine the ability of
      stressors to induce changes in the gut microbiota, we exposed mice to a prolonged
      restraint stressor and then characterized microbial populations in the intestines
      using both traditional culture techniques and bacterial tag-encoded FLX amplicon
      pyrosequencing (bTEFAP). Exposure to the stressor led to an overgrowth of
      facultatively anaerobic microbiota while at the same time significantly reducing
      microbial richness and diversity in the ceca of stressed mice. Some of these
      effects could be explained by a stressor-induced reduction in the relative
      abundance of bacteria in the family Porphyromonadaceae. To determine whether
      these alterations would lead to increased pathogen colonization, stressed mice,
      as well as nonstressed controls, were challenged orally with the enteric murine
      pathogen Citrobacter rodentium. Exposure to the restraint stressor led to a
      significant increase in C. rodentium colonization over that in nonstressed
      control mice. The increased colonization was associated with increased tumor
      necrosis factor alpha (TNF-alpha) gene expression in colonic tissue. Together,
      these data demonstrate that a prolonged stressor can significantly change the
      composition of the intestinal microbiota and suggest that this disruption of the
      microbiota increases susceptibility to an enteric pathogen.

PMID- 20145095
TI  - The K5 capsule of Escherichia coli strain Nissle 1917 is important in stimulating
      expression of Toll-like receptor 5, CD14, MyD88, and TRIF together with the
      induction of interleukin-8 expression via the mitogen-activated protein kinase
      pathway in epithelial cells.
AB  - Escherichia coli strain Nissle 1917, which has been widely used as a probiotic
      for the treatment of inflammatory bowel disorders, expresses a K5 capsule, the
      expression of which is often associated with extraintestinal and urinary tract
      isolates of E. coli. Previously, it had been shown that the expression of a K5
      capsule by Nissle 1917 was important in mediating interactions with epithelial
      cells and the extent of chemokine expression. In this paper, we show that
      infection with Nissle 1917 induces expression of Toll-like receptor 4 (TLR4) and
      TLR5 in Caco-2 cells and that maximal induction of TLR5 required the K5 capsule.
      In addition, purified K5 polysaccharide was capable of inducing expression of
      TLR5 and mCD14 and potentiated the activity of both TLR4 and TLR5 agonists to
      increase the proinflammatory response. Infection with Nissle 1917 also increased
      the expression of the adaptor molecules MyD88 and TRIF, which was K5 capsule
      dependent. By Western blot analysis, it was possible to show that induction of
      interleukin-8 by Nissle 1917 was predominantly through the mitogen-activated
      protein (MAP) kinase pathway and that expression of the K5 capsule was important
      for activation of the MAP kinase pathway. This paper provides new information on
      the function of the K5 capsule in mediating interactions between Nissle 1917 and
      epithelial cells and the mechanisms that underlie the probiotic properties of
      Nissle 1917.

PMID- 20145096
TI  - Extracellular vesicles from Cryptococcus neoformans modulate macrophage
      functions.
AB  - Cryptococcus neoformans and distantly related fungal species release
      extracellular vesicles that traverse the cell wall and contain a varied
      assortment of components, some of which have been associated with virulence.
      Previous studies have suggested that these extracellular vesicles are produced in
      vitro and during animal infection, but the role of vesicular secretion during the
      interaction of fungi with host cells remains unknown. In this report, we
      demonstrate by fluorescence microscopy that mammalian macrophages can incorporate
      extracellular vesicles produced by C. neoformans. Incubation of cryptococcal
      vesicles with murine macrophages resulted in increased levels of extracellular
      tumor necrosis factor alpha (TNF-alpha), interleukin-10 (IL-10), and transforming
      growth factor beta (TGF-beta). Vesicle preparations also resulted in a dose
      dependent stimulation of nitric oxide production by phagocytes, suggesting that
      vesicle components stimulate macrophages to produce antimicrobial compounds.
      Treated macrophages were more effective at killing C. neoformans yeast. Our
      results indicate that the extracellular vesicles of C. neoformans can stimulate
      macrophage function, apparently activating these phagocytic cells to enhance
      their antimicrobial activity. These results establish that cryptococcal vesicles
      are biologically active.

PMID- 20145097
TI  - UpaH is a newly identified autotransporter protein that contributes to biofilm
      formation and bladder colonization by uropathogenic Escherichia coli CFT073.
AB  - Escherichia coli is the primary cause of urinary tract infection (UTI) in the
      developed world. The major factors associated with virulence of uropathogenic E.
      coli (UPEC) are fimbrial adhesins, which mediate specific attachment to host
      receptors and trigger innate host responses. Another group of adhesins is
      represented by the autotransporter (AT) subgroup of proteins. In this study, we
      identified a new AT-encoding gene, termed upaH, present in a 6.5-kb unannotated
      intergenic region in the genome of the prototypic UPEC strain CFT073. Cloning and
      sequencing of the upaH gene from CFT073 revealed an intact 8.535-kb coding
      region, contrary to the published genome sequence. The upaH gene was widely
      distributed among a large collection of UPEC isolates as well as the E. coli
      Reference (ECOR) strain collection. Bioinformatic analyses suggest beta-helix as
      the predominant structure in the large N-terminal passenger (alpha) domain and a
      12-strand beta-barrel for the C-terminal beta-domain of UpaH. We demonstrated
      that UpaH is expressed at the cell surface of CFT073 and promotes biofilm
      formation. In the mouse UTI model, deletion of the upaH gene in CFT073 and in two
      other UPEC strains did not significantly affect colonization of the bladder in
      single-challenge experiments. However, in competitive colonization experiments,
      CFT073 significantly outcompeted its upaH isogenic mutant strain in urine and the
      bladder.

PMID- 20145098
TI  - Concomitant infection decreases the malaria burden but escalates relapsing fever
      borreliosis.
AB  - About 500 million cases of malaria occur annually. However, a substantial number
      of patients who actually have relapsing fever (RF) Borrelia infection can be
      misdiagnosed with malaria due to similar manifestations and geographic
      distributions of the two diseases. More alarmingly, a high prevalence of
      concomitant infections with malaria and RF Borrelia has been reported. Therefore,
      we used a mouse model to study the effects of such mixed infection. We observed a
      21-fold increase in spirochete titers, whereas the numbers of parasitized
      erythrocytes were reduced 15-fold. This may be explained by polarization of the
      host immune response toward the intracellular malaria parasite, resulting in
      unaffected extracellular spirochetes and hosts that succumb to sepsis. Mixed
      infection also resulted in severe malaria anemia with low hemoglobin levels, even
      though the parasite counts were low. Overall, coinfected animals had a higher
      fatality rate and shorter time to death than those with either malaria or RF
      single infection. Furthermore, secondary malaria infection reactivated a
      quiescent RF brain infection, which is the first evidence of a clinically and
      biologically relevant cue for reactivation of RF Borrelia infection. Our study
      highlights the importance of investigating concomitant infections in vivo to
      elucidate the immune responses that are involved in the clinical outcome.

PMID- 20145099
TI  - Inflammatory monocytes but not neutrophils are necessary to control infection
      with Toxoplasma gondii in mice.
AB  - Previous studies have suggested that both inflammatory monocytes and neutrophils
      are important for controlling acute toxoplasmosis in the mouse model. To test the
      role of these cell types, we used monoclonal antibody (MAb) RB6-8C5 to deplete
      both subsets of cells or MAb 1A8 to selectively remove neutrophils. RB6-8C5 MAb
      treated mice succumbed to oral infection with Toxoplasma gondii, similar to Ccr2(
      /-) mice, which are deficient in monocyte recruitment but have normal
      neutrophils. In contrast, mice treated with MAb 1A8 controlled parasite
      replication and survived acute infection. Ccr2(-/-) mice suffered from acute
      ileitis and inflammation in the spleen that was associated with a lack of
      inflammatory monocytes and elevated numbers of neutrophils. RB6-8C5 MAb-treated
      C57BL/6 mice also suffered from intestinal pathology and splenic damage, although
      this was less extensive due to the reduced numbers of neutrophils. Neutrophil
      depleted infected wild-type mice displayed no pathological changes, compared to
      untreated infected controls. Collectively, these observations demonstrate the
      critical role of inflammatory monocytes during the acute infection with the
      parasite T. gondii and reveal that neutrophils are not protective but rather
      contribute to the pathology.

PMID- 20145100
TI  - Molecular cloning, biochemical characterization, and partial protective immunity
      of the heme-binding glutathione S-transferases from the human hookworm Necator
      americanus.
AB  - Hookworm glutathione S-transferases (GSTs) are critical for parasite blood
      feeding and survival and represent potential targets for vaccination. Three
      cDNAs, each encoding a full-length GST protein from the human hookworm Necator
      americanus (and designated Na-GST-1, Na-GST-2, and Na-GST-3, respectively) were
      isolated from cDNA based on their sequence similarity to Ac-GST-1, a GST from the
      dog hookworm Ancylostoma caninum. The open reading frames of the three N.
      americanus GSTs each contain 206 amino acids with 51% to 69% sequence identity
      between each other and Ac-GST-1. Sequence alignment with GSTs from other
      organisms shows that the three Na-GSTs belong to a nematode-specific nu-class GST
      family. All three Na-GSTs, when expressed in Pichia pastoris, exhibited low lipid
      peroxidase and glutathione-conjugating enzymatic activities but high heme-binding
      capacities, and they may be involved in the detoxification and/or transport of
      heme. In two separate vaccine trials, recombinant Na-GST-1 formulated with
      Alhydrogel elicited 32 and 39% reductions in adult hookworm burdens (P < 0.05)
      following N. americanus larval challenge relative to the results for a group
      immunized with Alhydrogel alone. In contrast, no protection was observed in
      vaccine trials with Na-GST-2 or Na-GST-3. On the basis of these and other
      preclinical data, Na-GST-1 is under possible consideration for further vaccine
      development.

PMID- 20145102
TI  - Antagonist-agonist combinations as therapies for heroin addiction: back to the
      future?
AB  - Psychopharmacology is a powerful approach to the treatment of many psychiatric
      disorders. In this article I discuss the conceptual and practical issues in
      relation to the use of mu opioid receptor agonist, antagonist and partial agonist
      drugs in the treatment of opioid addiction, as this is one therapeutic area where
      all three types of agents are currently available. The choice of pharmacological
      agent is largely determined by patient profile, existence of ongoing drug misuse,
      and the kinetics of the drugs available. These principles, however, can be
      applied to other disorders as and when other pharmacological approaches become
      refined in these areas.

PMID- 20145103
TI  - BacMam-enabled LanthaScreen cellular assays for PI3K/Akt pathway compound
      profiling in disease-relevant cell backgrounds.
AB  - The authors recently reported the development and application of multiple
      LanthaScreen cellular assays to interrogate specific steps within the PI3K/Akt
      pathway. The importance of this signaling cascade in regulating fundamental
      aspects of cell growth and survival, as well as in the progression of cancer,
      underscores the need for portable cell-based assays for compound profiling in
      multiple disease-relevant cell backgrounds. To meet this need, the authors have
      now expanded their LanthaScreen assay platform across a variety of cell types
      using a gene delivery technology known as BacMam. Here, they have demonstrated
      the successful detection of Akt-dependent phosphorylation of PRAS40 at Thr246 in
      10 different cell lines harboring mutations known to activate the PI3K/Akt
      pathway. In addition, they generated inhibitory profiles of 17 known pathway
      inhibitors in these same cells to validate the approach of using the BacMam
      enabled LanthaScreen cellular assay format to rapidly profile compounds in
      disease-relevant cell types. Importantly, their results provide a broad
      illustration of how the genetic alterations that affect PI3K/Akt signaling can
      also influence the inhibitory profile of a given compound.

PMID- 20145101
TI  - Examination of type IV pilus expression and pilus-associated phenotypes in
      Kingella kingae clinical isolates.
AB  - Kingella kingae is a gram-negative bacterium that is being recognized
      increasingly as a cause of septic arthritis and osteomyelitis in young children.
      Previous work established that K. kingae expresses type IV pili that mediate
      adherence to respiratory epithelial and synovial cells. PilA1 is the major pilus
      subunit in K. kingae type IV pili and is essential for pilus assembly. To develop
      a better understanding of the role of K. kingae type IV pili during colonization
      and invasive disease, we examined a collection of clinical isolates for pilus
      expression and in vitro adherence. In addition, in a subset of isolates we
      performed nucleotide sequencing to assess the level of conservation of PilA1. The
      majority of respiratory and nonendocarditis blood isolates were piliated, while
      the majority of joint fluid, bone, and endocarditis blood isolates were
      nonpiliated. The piliated isolates formed either spreading/corroding or
      nonspreading/noncorroding colonies and were uniformly adherent, while the
      nonpiliated isolates formed domed colonies and were nonadherent. PilA1 sequence
      varied significantly from strain to strain, resulting in substantial variability
      in antibody reactivity. These results suggest that type IV pili may confer a
      selective advantage on K. kingae early in infection and a selective disadvantage
      on K. kingae at later stages in the pathogenic process. We speculate that PilA1
      is immunogenic during natural infection and undergoes antigenic variation to
      escape the immune response.

PMID- 20145104
TI  - Inhibition of respiratory growth and survival in yeast by dopamine and
      counteraction with ascorbate or glutathione.
AB  - Dopamine is a key monamine neurotransmitter, yet it can also exhibit toxicity to
      neuronal cells. There are suggestions that dopamine may be neurotoxic due to its
      propensity to induce the formation of reactive oxygen species, which may in turn
      adversely affect mitochondrial function and cell viability. In this study, the
      effects of dopamine or a dopamine reaction product on yeast growth and survival
      have been explored. Yeast is ideal for such a study because, unlike mammalian
      cells, yeast cells can be grown even when respiratory function is totally absent.
      Indeed, dopamine was found to be inhibitory to yeast growth in media where
      respiratory function was required and cytotoxic to yeast cells suspended in
      water. The inhibitory effects of dopamine were reduced greatly by the
      antioxidants ascorbate and glutathione, suggesting the involvement of reactive
      oxygen species in dopamine-mediated toxicity. It would appear that yeast may
      offer a convenient model to perform screens for further compounds that may
      provide protection against dopamine-mediated growth inhibition and toxicity.

PMID- 20145105
TI  - Constructive neutral evolution cannot explain current kinetoplastid panediting
      patterns.

PMID- 20145106
TI  - Paleobiology and the origins of avian flight.

PMID- 20145107
TI  - Targeting HIV-1 DNA integration by swapping tethers.

PMID- 20145108
TI  - Natural variation for seed dormancy in Arabidopsis is regulated by additive
      genetic and molecular pathways.
AB  - Timing of germination is presumably under strong natural selection as it
      determines the environmental conditions in which a plant germinates and initiates
      its postembryonic life cycle. To investigate how seed dormancy is controlled,
      quantitative trait loci (QTL) analyses has been performed in six Arabidopsis
      thaliana recombinant inbred line populations by analyzing them simultaneously
      using a mixed model QTL approach. The recombinant inbred line populations were
      derived from crosses between the reference accession Landsberg erecta (Ler) and
      accessions from different world regions. In total, 11 delay of germination (DOG)
      QTL have been identified, and nine of them have been confirmed by near isogenic
      lines (NILs). The absence of strong epistatic interactions between the different
      DOG loci suggests that they affect dormancy mainly by distinct genetic pathways.
      This was confirmed by analyzing the transcriptome of freshly harvested dry seeds
      of five different DOG NILs. All five DOG NILs showed discernible and different
      expression patterns compared with the expression of their genetic background Ler.
      The genes identified in the different DOG NILs represent largely different gene
      ontology profiles. It is proposed that natural variation for seed dormancy in
      Arabidopsis is mainly controlled by different additive genetic and molecular
      pathways rather than epistatic interactions, indicating the involvement of
      several independent pathways.

PMID- 20145109
TI  - Forebrain overexpression of CK1delta leads to down-regulation of dopamine
      receptors and altered locomotor activity reminiscent of ADHD.
AB  - Dopamine neurotransmission controls motor and perseverative behavior, is mediated
      by protein phosphorylation, and may be perturbed in disorders of attention and
      hyperactivity. To assess the role of casein kinase I (CK1) in the regulation of
      dopamine signaling, we generated a genetically modified mouse line that
      overexpresses CK1delta (CK1delta OE) specifically in the forebrain.
      Overexpression was confirmed both at the mRNA and at the protein levels. Under
      basal conditions, CK1delta OE mice exhibited horizontal and vertical
      hyperactivity, reduced anxiety, and nesting behavior deficiencies. The CK1delta
      OE mice also presented paradoxical responses to dopamine receptor stimulation,
      showing hypoactivity following injection of d-amphetamine or methylphenidate,
      indicating that CK1 activity has a profound effect on dopamine signaling in vivo.
      Interestingly, CK1delta overexpression led to significantly reduced D1R and D2R
      dopamine receptor levels. All together, under basal conditions and in response to
      drug stimulation, the behavioral phenotype of CK1delta OE mice is reminiscent of
      the symptoms and drug responses observed in attention-deficit/hyperactivity
      disorder and therefore the CK1delta OE mice appear to be a model for this
      disorder.

PMID- 20145111
TI  - ASK-ing EMT not to spread cancer.

PMID- 20145110
TI  - Abnormal development of the cerebral cortex and cerebellum in the setting of
      lamin B2 deficiency.
AB  - Nuclear lamins are components of the nuclear lamina, a structural scaffolding for
      the cell nucleus. Defects in lamins A and C cause an array of human diseases,
      including muscular dystrophy, lipodystrophy, and progeria, but no diseases have
      been linked to the loss of lamins B1 or B2. To explore the functional relevance
      of lamin B2, we generated lamin B2-deficient mice and found that they have severe
      brain abnormalities resembling lissencephaly, with abnormal layering of neurons
      in the cerebral cortex and cerebellum. This neuronal layering abnormality is due
      to defective neuronal migration, a process that is dependent on the organized
      movement of the nucleus within the cell. These studies establish an essential
      function for lamin B2 in neuronal migration and brain development.

PMID- 20145112
TI  - High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic,
      chromosome instability phenotype with later onset.
AB  - Analysis of chromosomal aberrations is used to determine the prognosis of
      neuroblastomas (NBs) and to aid treatment decisions. MYCN amplification (MNA)
      alone is an incomplete poor prognostic factor, and chromosome 11q status has
      recently been included in risk classification. We analyzed 165 NB tumors using
      high-density SNP microarrays and specifically compared the high-risk groups
      defined by MNA (n = 37) and 11q-deletion (n = 21). Median patient age at
      diagnosis was 21 months for MNA tumors and 42 months for 11q-deletion tumors, and
      median survival time after diagnosis was 16 months for MNA and 40 months for 11q
      deletion. Overall survival (at 8 years) was approximately 35% in both groups. MNA
      and 11q deletion were almost mutually exclusive; only one case harbored both
      aberrations. The numbers of segmental aberrations differed significantly; the MNA
      group had a median of four aberrations, whereas the 11q-deletion group had 12.
      The high frequency of chromosomal breaks in the 11q-deletion group is suggestive
      of a chromosomal instability phenotype gene located in 11q; one such gene, H2AFX,
      is located in 11q23.3 (within the 11q-deletion region). Furthermore, in the
      groups with segmental aberrations without MNA or 11q deletion, the tumors with
      17q gain have worse prognosis than those with segmental aberrations without 17q
      gain, which have a favorable outcome. This study has implications for therapy in
      different risk groups and stresses that genome-wide microarray analyses should be
      included in clinical management to fully evaluate risk, aid diagnosis, and guide
      treatment.

PMID- 20145113
TI  - Fitness flux and ubiquity of adaptive evolution.
AB  - Natural selection favors fitter variants in a population, but actual evolutionary
      processes may decrease fitness by mutations and genetic drift. How is the
      stochastic evolution of molecular biological systems shaped by natural selection?
      Here, we derive a theorem on the fitness flux in a population, defined as the
      selective effect of its genotype frequency changes. The fitness-flux theorem
      generalizes Fisher's fundamental theorem of natural selection to evolutionary
      processes including mutations, genetic drift, and time-dependent selection. It
      shows that a generic state of populations is adaptive evolution: there is a
      positive fitness flux resulting from a surplus of beneficial over deleterious
      changes. In particular, stationary nonequilibrium evolution processes are
      predicted to be adaptive. Under specific nonstationary conditions, notably during
      a decrease in population size, the average fitness flux can become negative. We
      show that these predictions are in accordance with experiments in bacteria and
      bacteriophages and with genomic data in Drosophila. Our analysis establishes
      fitness flux as a universal measure of adaptation in molecular evolution.

PMID- 20145114
TI  - Only two amino acids are essential for cytolytic toxin recognition of cholesterol
      at the membrane surface.
AB  - The recognition and binding of cholesterol is an important feature of many
      eukaryotic, viral, and prokaryotic proteins, but the molecular details of such
      interactions are understood only for a few proteins. The pore-forming cholesterol
      dependent cytolysins (CDCs) contribute to the pathogenic mechanisms of a large
      number of Gram-positive bacteria. Cholesterol dependence of the CDC mechanism is
      a hallmark of these toxins, yet the identity of the CDC cholesterol recognition
      motif has remained elusive. A detailed analysis of membrane interactive
      structures at the tip of perfringolysin O (PFO) domain 4 reveals that a threonine
      leucine pair mediates CDC recognition of and binding to membrane cholesterol.
      This motif is conserved in all known CDCs and conservative changes in its
      sequence or order are not well tolerated. Thus, the Thr-Leu pair constitutes a
      common structural basis for mediating CDC-cholesterol recognition and binding,
      and defines a unique paradigm for membrane cholesterol recognition by surface
      binding proteins.

PMID- 20145115
TI  - Hippocampus and configural-relational information: a relationship confined to
      memory?

PMID- 20145117
TI  - Comment re: HMGA2 is a negative regulator of DNA-PK pathway.

PMID- 20145116
TI  - Structural determinants of growth factor binding and specificity by VEGF receptor
      2.
AB  - Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel
      formation through activation of three receptor tyrosine kinases, VEGFR-1, -2, and
      -3. The extracellular domain of VEGF receptors consists of seven immunoglobulin
      homology domains, which, upon ligand binding, promote receptor dimerization.
      Dimerization initiates transmembrane signaling, which activates the intracellular
      tyrosine kinase domain of the receptor. VEGF-C stimulates lymphangiogenesis and
      contributes to pathological angiogenesis via VEGFR-3. However, proteolytically
      processed VEGF-C also stimulates VEGFR-2, the predominant transducer of signals
      required for physiological and pathological angiogenesis. Here we present the
      crystal structure of VEGF-C bound to the VEGFR-2 high-affinity-binding site,
      which consists of immunoglobulin homology domains D2 and D3. This structure
      reveals a symmetrical 22 complex, in which left-handed twisted receptor domains
      wrap around the 2-fold axis of VEGF-C. In the VEGFs, receptor specificity is
      determined by an N-terminal alpha helix and three peptide loops. Our structure
      shows that two of these loops in VEGF-C bind to VEGFR-2 subdomains D2 and D3,
      while one interacts primarily with D3. Additionally, the N-terminal helix of VEGF
      C interacts with D2, and the groove separating the two VEGF-C monomers binds to
      the D2/D3 linker. VEGF-C, unlike VEGF-A, does not bind VEGFR-1. We therefore
      created VEGFR-1/VEGFR-2 chimeric proteins to further study receptor specificity.
      This biochemical analysis, together with our structural data, defined VEGFR-2
      residues critical for the binding of VEGF-A and VEGF-C. Our results provide
      significant insights into the structural features that determine the high
      affinity and specificity of VEGF/VEGFR interactions.

PMID- 20145118
TI  - Estrogen suppresses MLK3-mediated apoptosis sensitivity in ER+ breast cancer
      cells.
AB  - Little knowledge exists about the mechanisms by which estrogen can impede
      chemotherapy-induced cell death of breast cancer cells. 17beta-Estradiol (E(2))
      hinders cytotoxic drug-induced cell death in estrogen receptor-positive (ER(+))
      breast cancer cells. We noted that the activity of the proapoptotic mixed lineage
      kinase 3 (MLK3) kinase was relatively higher in estrogen receptor-negative (ER(
      )) breast tumors, suggesting that E(2) might inhibit MLK3 activity. The kinase
      activities of MLK3 and its downstream target, c-Jun NH(2)-terminal kinase, were
      rapidly inhibited by E(2) in ER(+) but not in ER(-) cells. Specific knockdown of
      AKT1/2 prevented MLK3 inhibition by E(2), indicating that AKT mediated this
      event. Furthermore, MLK3 inhibition by E(2) involved phosphorylation of MLK3
      Ser(674) by AKT, attenuating the proapoptotic function of MLK3. We found that a
      pan-MLK inhibitor (CEP-11004) limited Taxol-induced cell death and that E(2)
      accentuated this limitation. Taken together, our findings indicate that E(2)
      inhibits the proapoptotic function of MLK3 as a mechanism to limit cytotoxic drug
      induced death of ER(+) breast cancer cells.

PMID- 20145119
TI  - Tumor detection by imaging proteolytic activity.
AB  - The cell surface protease membrane-type serine protease-1 (MT-SP1), also known as
      matriptase, is often upregulated in epithelial cancers. We hypothesized that
      dysregulation of MT-SP1 with regard to its cognate inhibitor hepatocyte growth
      factor activator inhibitor-1 (HAI-1), a situation that increases proteolytic
      activity, might be exploited for imaging purposes to differentiate malignant from
      normal tissue. In this study, we show that MT-SP1 is active on cancer cells and
      that its activity may be targeted in vivo for tumor detection. A proteolytic
      activity assay with several MT-SP1-positive human cancer cell lines showed that
      MT-SP1 antibodies that inhibit recombinant enzyme activity in vitro also bind and
      inhibit the full-length enzyme expressed on cells. In contrast, in the same
      assay, MT-SP1-negative cancer cell lines were inactive. Fluorescence microscopy
      confirmed the cell surface localization of labeled antibodies bound to MT-SP1
      positive cells. To evaluate in vivo targeting capability, 0.7 to 2 nmoles of
      fluorescently labeled antibodies were administered to mice bearing tumors that
      were positive or negative for MT-SP1. Antibodies localized to MT-SP1-positive
      tumors (n = 3), permitting visualization of MT-SP1 activity, whereas MT-SP1
      negative tumors (n = 2) were not visualized. Our findings define MT-SP1 activity
      as a useful biomarker to visualize epithelial cancers using a noninvasive
      antibody-based method.

PMID- 20145120
TI  - R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and
      prolongs survival in models of metastatic breast cancer.
AB  - Accumulating evidence suggests important roles for the receptor tyrosine kinase
      Axl in cancer progression, invasion, metastasis, drug resistance, and patient
      mortality, highlighting Axl as an attractive target for therapeutic development.
      We have generated and characterized a potent and selective small-molecule
      inhibitor, R428, that blocks the catalytic and procancerous activities of Axl.
      R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events,
      including Akt phosphorylation, breast cancer cell invasion, and proinflammatory
      cytokine production. Pharmacologic investigations revealed favorable exposure
      after oral administration such that R428-treated tumors displayed a dose
      dependent reduction in expression of the cytokine granulocyte macrophage colony
      stimulating factor and the epithelial-mesenchymal transition transcriptional
      regulator Snail. In support of an earlier study, R428 inhibited angiogenesis in
      corneal micropocket and tumor models. R428 administration reduced metastatic
      burden and extended survival in MDA-MB-231 intracardiac and 4T1 orthotopic
      (median survival, >80 days compared with 52 days; P < 0.05) mouse models of
      breast cancer metastasis. Additionally, R428 synergized with cisplatin to enhance
      suppression of liver micrometastasis. Our results show that Axl signaling
      regulates breast cancer metastasis at multiple levels in tumor cells and tumor
      stromal cells and that selective Axl blockade confers therapeutic value in
      prolonging survival of animals bearing metastatic tumors.

PMID- 20145121
TI  - Blockade of tumor necrosis factor alpha signaling in tumor-associated macrophages
      as a radiosensitizing strategy.
AB  - Most cancer patients receive radiotherapy during the course of their disease.
      Improvements in the therapeutic index have been based mainly on physical
      improvements in delivery, as radiosensitizer development to target tumor cells
      has yet to yield effective agents. Recent investigations have focused on the
      tumor stroma as a target for radiosensitization. Here, we report that depletion
      of tumor-associated macrophages (TAMvarphi) by systemic or local injection of the
      macrophage-depleting liposomal clodronate before radiotherapy can increase the
      antitumor effects of ionizing radiation (IR), either as a large single dose (20
      Gy) or as a fractionated dose (2 Gy x 10). Coimplantation of tumor cells with
      bone marrow-derived macrophages (BMDMvarphi) increased tumor radioresistance.
      Studies using mice with germline deletions in tumor necrosis factor receptors 1
      and 2 (TNFR1,2(-/-)) or TNFalpha (TNF(-/-)), or treatment of wild-type mice with
      a soluble TNF receptor fusion protein (Enbrel), revealed that radioresistance
      mediated by BMDMvarphi required intact TNFalpha signaling. Radiation exposure
      upregulated vascular endothelial growth factor (VEGF) in macrophages and VEGF
      neutralizing antibodies enhanced the antitumor response to IR. Thus, the
      radioprotective effect of TNFalpha was mediated by TAM-produced VEGF. Our
      findings offer a mechanistic basis to target macrophage populations generally or
      TNFalpha-induced macrophage VEGF specifically as tractable strategies to improve
      the efficacy of radiotherapy.

PMID- 20145122
TI  - Genetic polymorphisms in vitamin D receptor VDR/RXRA influence the likelihood of
      colon adenoma recurrence.
AB  - Low circulating levels of vitamin D affect colorectal cancer risk. The biological
      actions of the hormonal form of vitamin D, 1,25(OH)(2)D(3), are mediated by the
      vitamin D receptor (VDR), which heterodimerizes with retinoid X receptors (RXR).
      Using a single nucleotide polymorphism (SNP) tagging approach, we assessed the
      association between genetic variations in RXRA and VDR and odds of recurrent
      (metachronous) colorectal neoplasia in a pooled population of two studies. A
      total of 32 tag SNPs in RXRA and 42 in VDR were analyzed in 1,439 participants. A
      gene-level association was observed for RXRA and any (P = 0.04) or proximal (P =
      0.03) metachronous neoplasia. No gene-level associations were observed for VDR,
      nor was any single SNP in VDR related to any metachronous adenoma after
      correction for multiple comparisons. In contrast, the association between RXRA
      SNP rs7861779 and proximal metachronous neoplasia was of borderline statistical
      significance [odds ratio (OR), 0.68; 95% confidence interval (95% CI), 0.53-0.86;
      unadjusted P = 0.001; adjusted P = 0.06], including when observed independently
      in each individual study. Haplotypes within linkage blocks of RXRA support an
      approximately 30% reduction in odds of metachronous neoplasia arising in the
      proximal colon among carriers of specific haplotypes, which was strongest
      (OR(proximal), 0.67; 95% CI, 0.52-0.86) for carriers of a CGGGCA haplotype
      (rs1805352, rs3132297, rs3132296, rs3118529, rs3118536, and rs7861779). Our
      results indicate that allelic variation in RXRA affects metachronous colorectal
      neoplasia, perhaps of particular importance in the development of proximal
      lesions.

PMID- 20145123
TI  - Tumor suppressor HLJ1 binds and functionally alters nucleophosmin via activating
      enhancer binding protein 2alpha complex formation.
AB  - HLJ1, a member of the heat shock protein 40 chaperone family, is a newly
      identified tumor suppressor that has been implicated in tumorigenesis and
      metastasis in non-small cell lung cancer. However, the mechanism of HLJ1 action
      is presently obscure. In this study, we report that HLJ1 specifically interacts
      with the nuclear protein nucleophosmin (NPM1), forming a multiprotein complex
      that alters the nucleolar distribution and oligomerization state of NPM1.
      Enforced accumulation of NPM1 oligomers by overexpression in weakly invasive but
      high HLJ1-expressing cells induced the activity of signal transducer and
      activator of transcription 3 (STAT3) and increased cellular migration,
      invasiveness, and colony formation. Furthermore, silencing HLJ1 accelerated NPM1
      oligomerization, inhibited the activity of transcription corepressor activating
      enhancer binding protein 2alpha (AP-2alpha), and increased the activities of
      matrix metalloproteinase-2 (MMP-2) and STAT3. Our findings suggest that HLJ1
      switches the role of NPM1, which can act as tumor suppressor or oncogene, by
      modulating the oligomerization of NPM1 via HLJ1-NPM1 heterodimer formation and
      recruiting AP-2alpha to the MMP-2 promoter.

PMID- 20145124
TI  - NOTCH signaling is required for formation and self-renewal of tumor-initiating
      cells and for repression of secretory cell differentiation in colon cancer.
AB  - NOTCH signaling is critical for specifying the intestinal epithelial cell lineage
      and for initiating colorectal adenomas and colorectal cancers (CRC). Based on
      evidence that NOTCH is important for the maintenance and self-renewal of cancer
      initiating cells in other malignancies, we studied the role of NOTCH signaling in
      colon cancer-initiating cells (CCIC). Tumors formed by CCICs maintain many
      properties of the primary CRCs from which they were derived, such as glandular
      organization, cell polarity, gap junctions, and expression of characteristic CRC
      molecular markers. Furthermore, CCICs have the property of self-renewal. In this
      study, we show that NOTCH signaling is 10- to 30-fold higher in CCIC compared
      with widely used colon cancer cell lines. Using small-molecule inhibition and
      short hairpin RNA knockdown, we show that NOTCH prevents CCIC apoptosis through
      repression of cell cycle kinase inhibitor p27 and transcription factor ATOH1.
      NOTCH is also critical to intrinsic maintenance of CCIC self-renewal and the
      repression of secretory cell lineage differentiation genes such as MUC2. Our
      findings describe a novel human cell system to study NOTCH signaling in CRC tumor
      initiation and suggest that inhibition of NOTCH signaling may improve CRC
      chemoprevention and chemotherapy.

PMID- 20145126
TI  - Activation of the integrin effector kinase focal adhesion kinase in cancer cells
      is regulated by crosstalk between protein kinase Calpha and the PDZ adapter
      protein mda-9/Syntenin.
AB  - Aberrant adhesion signaling pathways in cancer cells underlie their deadly
      invasive capabilities. The adhesion-related PDZ adapter protein mda-9/syntenin is
      a positive regulator of cancer cell progression in breast cancer, melanoma, and
      other human cancers. In this study, we report that mda-9/syntenin mediates
      adhesion-mediated activation of protein kinase Calpha (PKCalpha) and focal
      adhesion kinase (FAK) by fibronectin (FN) in human breast cancer and melanoma
      cells. FN rapidly stimulated the expression of mda-9/syntenin and the activation
      of PKCalpha prior to activation of FAK. Inhibiting PKCalpha suppressed basal or
      FN-induced expression of mda-9/syntenin, as well as cell migration and invasion
      toward FN stimulated by mda-9/syntenin. Several lines of evidence suggested that
      activation of PKCalpha and expression of mda-9/syntenin were interdependent.
      First, mda-9/syntenin inhibition suppressed basal or FN-induced phosphorylation
      of PKCalpha at Thr(638/641), whereas PKCalpha inhibition suppressed basal or FN
      induced expression of mda-9/syntenin. Second, inhibiting either mda-9/syntenin or
      PKCalpha suppressed FN-induced formation of integrin-beta(1)/FAK/c-Src signaling
      complexes. Third, inhibiting either mda-9/syntenin or PKCalpha suppressed FN
      induced phosphorylation of FAK Tyr(397) and c-Src Tyr(416) and the induction of
      downstream effector signals to p38 and mitogen-activated protein kinase, Cdc42,
      and NF-kappaB. In summary, our findings offer evidence that mda-9/syntenin acts
      as a molecular adaptor linking PKCalpha and FAK activation in a pathway of FN
      adhesion by human breast cancer and melanoma cells.

PMID- 20145127
TI  - Reduced levels of IGF-I mediate differential protection of normal and cancer
      cells in response to fasting and improve chemotherapeutic index.
AB  - Inhibitors of the insulin-like growth factor-I (IGF-I) receptor have been widely
      studied for their ability to enhance the killing of a variety of malignant cells,
      but whether IGF-I signaling differentially protects the host and cancer cells
      against chemotherapy is unknown. Starvation can protect mice, but not cancer
      cells, against high-dose chemotherapy [differential stress resistance (DSR)].
      Here, we offer evidence that IGF-I reduction mediates part of the starvation
      dependent DSR. A 72-hour fast in mice reduced circulating IGF-I by 70% and
      increased the level of the IGF-I inhibitor IGFBP-1 by 11-fold. LID mice, with a
      70% to 80% reduction in circulating IGF-I levels, were protected against three of
      four chemotherapy drugs tested. Restoration of IGF-I was sufficient to reverse
      the protective effect of fasting. Sixty percent of melanoma-bearing LID mice
      treated with doxorubicin achieved long-term survival whereas all control mice
      died of either metastases or chemotherapy toxicity. Reducing IGF-I/IGF-I
      signaling protected primary glia, but not glioma cells, against cyclophosphamide
      and protected mouse embryonic fibroblasts against doxorubicin. Further, S.
      cerevisiae lacking homologs of IGF-I signaling proteins were protected against
      chemotherapy-dependent DNA damage in a manner that could be reversed by
      expressing a constitutively active form of Ras. We conclude that normal cells and
      mice can be protected against chemotherapy-dependent damage by reducing
      circulating IGF-I levels and by a mechanism that involves downregulation of proto
      oncogene signals.

PMID- 20145128
TI  - Noninvasive detection of target modulation following phosphatidylinositol 3
      kinase inhibition using hyperpolarized 13C magnetic resonance spectroscopy.
AB  - Numerous mechanism-based anticancer drugs that target the phosphatidylinositol 3
      kinase (PI3K) pathway are in clinical trials. However, it remains challenging to
      assess responses by traditional imaging methods. Here, we show for the first time
      the efficacy of hyperpolarized (13)C magnetic resonance spectroscopy (MRS) in
      detecting the effect of PI3K inhibition by monitoring hyperpolarized [1
      (13)C]lactate levels produced from hyperpolarized [1-(13)C]pyruvate through
      lactate dehydrogenase (LDH) activity. In GS-2 glioblastoma cells, PI3K inhibition
      by LY294002 or everolimus caused hyperpolarized lactate to drop to 42 +/- 12% and
      to 76 +/- 5%, respectively. In MDA-MB-231 breast cancer cells, hyperpolarized
      lactate dropped to 71 +/- 15% after treatment with LY294002. These reductions
      were correlated with reductions in LDH activity to 48 +/- 4%, 63 +/- 4%, and 69
      +/- 12%, respectively, and were associated with a drop in levels of LDHA mRNA and
      LDHA and hypoxia-inducible factor-1alpha proteins. Supporting these findings,
      tumor growth inhibition achieved by everolimus in murine GS-2 xenografts was
      associated with a drop in the hyperpolarized lactate-to-pyruvate ratio detected
      by in vivo MRS imaging, whereas an increase in this ratio occurred with tumor
      growth in control animals. Taken together, our findings illustrate the
      application of hyperpolarized (13)C MRS of pyruvate to monitor alterations in
      LDHA activity and expression caused by PI3K pathway inhibition, showing the
      potential of this method for noninvasive imaging of drug target modulation.

PMID- 20145129
TI  - Interaction of developmental transcription factor HOXC11 with steroid receptor
      coactivator SRC-1 mediates resistance to endocrine therapy in breast cancer
      [corrected].
AB  - Mechanisms of acquired resistance to endocrine therapy in breast cancer, a major
      clinical challenge, are poorly understood. We have used a mass spectrometry-based
      screen to identify proteins that are associated with the endocrine-resistant
      phenotype. In this study, we report the identification of a novel pathway of
      resistance to endocrine therapy involving interactions of the developmental
      transcription HOXC11 with the steroid receptor coactivator protein SRC-1, which
      is a strong predictor of reduced disease-free survival in breast cancer patients.
      HOXC11 and SRC-1 cooperate to regulate expression of the calcium-binding protein
      S100beta in resistant breast cancer cells. Nuclear HOXC11 and S100beta were found
      to strongly predict poor disease-free survival in breast cancer patients (n =
      560; hazard ratios: 5.79 and 5.82, respectively; P < 0.0001). Elevated serum
      levels of S100beta detected in patients also predicted reduced disease-free
      survival (n = 80; hazard ratio: 5.3; P = 0.004). Our findings define a
      biomolecular interaction network that drives an adaptive response to endocrine
      therapy with negative consequences for survival in breast cancer.

PMID- 20145130
TI  - The bioreductive prodrug PR-104A is activated under aerobic conditions by human
      aldo-keto reductase 1C3.
AB  - PR-104, currently in phase II clinical trials, is a phosphate ester pre-prodrug
      which is converted in vivo to its cognate alcohol, PR-104A, a prodrug designed to
      exploit tumor hypoxia. Bioactivation occurs via one-electron reduction to DNA
      crosslinking metabolites in the absence of oxygen. However, certain tumor cell
      lines activate PR-104A in the presence of oxygen, suggesting the existence of an
      aerobic nitroreductase. Microarray analysis identified a cluster of five aldo
      keto reductase (AKR) family members whose expressions correlated with aerobic
      metabolism of PR-104A. Plasmid-based expression of candidate genes identified
      aldo-keto reductase 1C3 as a novel nitroreductase. AKR1C3 protein was detected by
      Western blot in 7 of 23 cell lines and correlated with oxic PR-104A metabolism,
      an activity which could be partially suppressed by Nrf2 RNAi knockdown (or
      induced by Keap1 RNAi), indicating regulation by the ARE pathway. AKR1C3 was
      unable to sensitize cells to 10 other bioreductive prodrugs and was associated
      with single-agent PR-104 activity across a panel of 9 human tumor xenograft
      models. Overexpression in two AKR1C3-negative tumor xenograft models strongly
      enhanced PR-104 antitumor activity. A population level survey of AKR1C3
      expression in 2,490 individual cases across 19 cancer types using tissue
      microarrays revealed marked upregulation of AKR1C3 in a subset including
      hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma. A
      survey of normal tissue AKR1C3 expression suggests the potential for tumor
      selective PR-104A activation by this mechanism. These findings have significant
      implications for the clinical development of PR-104.

PMID- 20145131
TI  - Regulation of p53 family member isoform DeltaNp63alpha by the nuclear factor
      kappaB targeting kinase IkappaB kinase beta.
AB  - The p53 family gene p63 plays an instrumental role in cellular stress responses
      including responses to DNA damage. In addition to encoding a full-length
      transcriptional activator, p63 also encodes several dominant inhibitory isoforms
      including the isoform DeltaNp63alpha, the function of which is not fully
      understood. DeltaNp63alpha is degraded in response to DNA damage, thereby
      enabling an effective cellular response to genotoxic agents. Here, we identify a
      key molecular mechanism underlying regulation of DeltaNp63alpha expression in
      response to chemotherapeutic agents or tumor necrosis factor-alpha. We found that
      DeltaNp63alpha interacts with IkappaB kinase (IKK), a multisubunit protein kinase
      that consists of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory
      subunit, IKKgamma. The IKKbeta kinase promotes ubiquitin-mediated proteasomal
      degradation of DeltaNp63alpha, whereas a kinase-deficient mutant IKKbeta-K44A
      fails to do so. Cytokine- or chemotherapy-induced stimulation of IKKbeta caused
      degradation of DeltaNp63alpha and augmented transactivation of p53 family-induced
      genes involved in the cellular response to DNA damage. Conversely, IKKbeta
      inhibition attenuated cytokine- or chemotherapy-induced degradation of
      DeltaNp63alpha. Our findings show that IKKbeta plays an essential role in
      regulating DeltaNp63alpha in response to extrinsic stimuli. IKK activation
      represents one mechanism by which levels of DeltaNp63alpha can be reduced,
      thereby rendering cells susceptible to cell death in the face of cellular stress
      or DNA damage.

PMID- 20145132
TI  - miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF
      pathway in head and neck carcinoma.
AB  - MicroRNAs (miRNA) are endogenously expressed noncoding RNAs with important
      biological and pathological functions that are yet to be fully defined. This
      study investigated alterations in miRNA expression in head and neck squamous cell
      carcinoma (HNSCC), the incidence of which is rising throughout the world. Initial
      screening and subsequent analysis identified a panel of aberrantly expressed
      miRNAs in HNSCC tissues, with miR-31 among the most markedly upregulated. Ectopic
      expression of miR-31 increased the oncogenic potential of HNSCC cells under
      normoxic conditions in cell culture or tumor xenografts. Conversely, blocking miR
      31 expression reduced the growth of tumor xenografts. The in silico analysis
      suggested that miR-31 may target the 3' untranslated region (UTR) of factor
      inhibiting hypoxia-inducible factor (FIH), a hypoxia-inducible factor (HIF)
      regulatory factor that inhibits the ability of HIF to act as a transcriptional
      regulator under normoxic conditions. In support of this likelihood, miR-31
      expression repressed FIH expression and mutations within the predictive miR-31
      target site in the FIH 3' UTR abrogated FIH repression. Furthermore, miR-31
      expression increased HIF transactivation activity. We found that FIH suppressed
      oncogenic phenotypes under normoxic conditions and that this activity was
      abrogated by functional mutations. Lastly, increased miR-31 expression was
      correlated with decreased levels of FIH in tumor tissues. Our findings suggest
      that miR-31 contributes to the development of HNSCC by impeding FIH to activate
      HIF under normoxic conditions.

PMID- 20145134
TI  - Oncolysis of prostate cancers induced by vesicular stomatitis virus in PTEN
      knockout mice.
AB  - Vesicular stomatitis virus (VSV) is an oncolytic virus which selectively infects
      and kills cancer cells. The goal of the present study was to determine the safety
      and efficacy of VSV treatment of prostate tumors that arise in situ in
      immunocompetent, transgenic prostate-specific PTEN-null (PTEN(-/-)) mice.
      Interferon-sensitive VSV(AV3 strain), which expresses luciferase, was injected
      intraprostatically into tumor-bearing PTEN(-/-) and control mice and then
      monitored for tissue bioluminescence over 96 hours. Virus readily dispersed
      throughout the bodies of mice after only 3 hours; however, it persisted at high
      levels for >72 hours in PTEN(-/-) mice, but at relatively low levels and for only
      approximately 48 hours in controls. Plaque assays provided a similar pattern,
      with much higher concentrations of replicating virus in prostates of PTEN(-/-)
      mice than in controls. Transient, low levels of virus were detected in the
      spleens of both groups. Apoptotic analyses by terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling staining revealed that VSV(AV3) is
      able to selectively infect and kill prostate cells in PTEN(-/-) mice, while
      sparing normal cells in control mice. The primary mechanism for cell kill is
      apparently apoptotic oncolysis as opposed to neutrophil invasion as has been
      reported using xenograft models. These results suggest that control of locally
      advanced human prostate cancer may be achievable through intraprostatic injection
      and amplification of a safe oncolytic virus, such as VSV(AV3).

PMID- 20145133
TI  - An ets2-driven transcriptional program in tumor-associated macrophages promotes
      tumor metastasis.
AB  - Tumor-associated macrophages (TAM) are implicated in breast cancer metastasis,
      but relatively little is known about the underlying genes and pathways that are
      involved. The transcription factor Ets2 is a direct target of signaling pathways
      involved in regulating macrophage functions during inflammation. We conditionally
      deleted Ets in TAMs to determine its function at this level on mouse mammary
      tumor growth and metastasis. Ets2 deletion in TAMs decreased the frequency and
      size of lung metastases in three different mouse models of breast cancer
      metastasis. Expression profiling and chromatin immunoprecipitation assays in
      isolated TAMs established that Ets2 repressed a gene program that included
      several well-characterized inhibitors of angiogenesis. Consistent with these
      results, Ets2 ablation in TAMs led to decreased angiogenesis and decreased growth
      of tumors. An Ets2-TAM expression signature consisting of 133 genes was
      identified within human breast cancer expression data which could retrospectively
      predict overall survival of patients with breast cancer in two independent data
      sets. In summary, we identified Ets2 as a central driver of a transcriptional
      program in TAMs that acts to promote lung metastasis of breast tumors.

PMID- 20145135
TI  - Heterogeneous nuclear ribonucleoprotein H blocks MST2-mediated apoptosis in
      cancer cells by regulating A-Raf transcription.
AB  - A-Raf belongs to the family of oncogenic Raf kinases that are involved in
      mitogenic signaling by activating the mitogen-activated protein
      (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway. Low
      kinase activity of A-Raf toward MEK suggested that A-Raf might have alternative
      functions. Here, we show that A-Raf prevents cancer cell apoptosis contingent on
      the expression of the heterogeneous nuclear ribonucleoprotein H (hnRNP H) splice
      factor, which is required for the correct transcription and expression of a-raf.
      Apoptosis was prevented by A-Raf through sequestration and inactivation of the
      proapoptotic MST2 kinase. Small interfering RNA-mediated knockdown of hnRNP H or
      A-Raf resulted in MST2-dependent apoptosis. In contrast, enforced expression of
      either hnRNP H or A-Raf partially counteracted apoptosis induced by etoposide. In
      vivo expression studies of colon specimens corroborated the overexpression of
      hnRNP H in malignant tissues and its correlation with A-Raf levels. Our findings
      define a novel mechanism that is usurped in tumor cells to escape naturally
      imposed apoptotic signals.

PMID- 20145136
TI  - Identification of EP4 as a potential target for the treatment of castration
      resistant prostate cancer using a novel xenograft model.
AB  - More effective therapeutic approaches for castration-resistant prostate cancer
      (CRPC) are urgently needed, thus reinforcing the need to understand how prostate
      tumors progress to castration resistance. We have established a novel mouse
      xenograft model of prostate cancer, KUCaP-2, which expresses the wild-type
      androgen receptor (AR) and which produces the prostate-specific antigen (PSA). In
      this model, tumors regress soon after castration, but then reproducibly restore
      their ability to proliferate after 1 to 2 months without AR mutation, mimicking
      the clinical behavior of CRPC. In the present study, we used this model to
      identify novel therapeutic targets for CRPC. Evaluating tumor tissues at various
      stages by gene expression profiling, we discovered that the prostaglandin E
      receptor EP4 subtype (EP4) was significantly upregulated during progression to
      castration resistance. Immunohistochemical results of human prostate cancer
      tissues confirmed that EP4 expression was higher in CRPC compared with hormone
      naive prostate cancer. Ectopic overexpression of EP4 in LNCaP cells (LNCaP-EP4
      cells) drove proliferation and PSA production in the absence of androgen
      supplementation in vitro and in vivo. Androgen-independent proliferation of LNCaP
      EP4 cells was suppressed when AR expression was attenuated by RNA interference.
      Treatment of LNCaP-EP4 cells with a specific EP4 antagonist, ONO-AE3-208,
      decreased intracellular cyclic AMP levels, suppressed PSA production in vitro,
      and inhibited castration-resistant growth of LNCaP-EP4 or KUCaP-2 tumors in vivo.
      Our findings reveal that EP4 overexpression, via AR activation, supports an
      important mechanism for castration-resistant progression of prostate cancer.
      Furthermore, they prompt further evaluation of EP4 antagonists as a novel
      therapeutic modality to treat CRPC.

PMID- 20145137
TI  - Antiestrogens induce transforming growth factor beta-mediated immunosuppression
      in breast cancer.
AB  - Antiestrogens are universally used to treat estrogen receptor--positive breast
      cancer, but relapses occur commonly due to the development of drug resistance.
      The ability of antiestrogen to induce transforming growth factor beta (TGFbeta)
      in breast cancer cells may be relevant to the emergence of resistance, not only
      at the level of cell autonomous effects of TGFbeta on cancer progression but also
      at the level of its effects on the host immune system. To evaluate the potential
      role of tumor-derived, antiestrogen-induced TGFbeta as an immune suppressor, we
      established in vitro mixed lymphocyte tumor reactions (MLTR) using MCF-7 cells
      and peripheral blood mononuclear cells (PBMC), as well as tumor tissue and
      autologous tumor infiltrating lymphocytes (TIL) obtained from primary breast
      cancer biopsies. In allogeneic MLTR, antiestrogen-treated MCF-7 cells caused
      downregulation of the effector molecules granzyme B, perforin, and Fas ligand in
      CD8(+) T cells, and suppressed the generation of cytotoxic effector cells in a
      TGFbeta-dependent manner. Furthermore, we documented induction of regulatory T
      cells in CD4(+) T cells, based on Foxp3 expression and T-cell activation in
      cocultures. In autologous MLTR, antiestrogen treatment gave rise to enhanced
      Foxp3 expression of TIL/PBMC and decreased the number of apoptotic tumor cells.
      These effects were reversed by addition of a TGFbeta neutralizing antibody. Our
      findings offer evidence that antiestrogen induces immunosuppression in the tumor
      microenvironment, through a TGFbeta-dependent mechanism that may contribute to
      the development of antiestrogen resistance in breast cancer.

PMID- 20145138
TI  - Common genetic variants associated with breast cancer and mammographic density
      measures that predict disease.
AB  - Mammographic density for age and body mass index (BMI) is a heritable risk factor
      for breast cancer. We aimed to determine if recently identified common variants
      associated with small gradients in breast cancer risk are associated with
      mammographic density. We genotyped 497 monozygotic and 330 dizygotic twin pairs
      and 634 of their sisters from 903 families for 12 independent variants.
      Mammographic dense area, percent dense area, and nondense area were measured by
      three observers using a computer-thresholding technique. Associations with
      mammographic density measures adjusted for age, BMI, and other determinants were
      estimated (a) cross-sectionally using a multivariate normal model for pedigree
      analysis (P(x)), (b) between sibships, and (c) within sibships using orthogonal
      transformations of outcomes and exposures. A combined test of association (P(c))
      was derived using the independent estimates from b and c. We tested if the
      distributions of P values across variants differed from the uniform distribution
      (P(u)). For dense area and percent dense area, the distributions of P(c) values
      were not uniform (both P(u) <0.007). Consistent with their breast cancer
      associations, rs3817198 (LSP1) and rs13281615 (8q) were associated with dense
      area and percent dense area (all P(x) and P(c) <0.05), and rs889312 (MAP3K1),
      rs2107425 (H19), and rs17468277 (CASP8) were marginally associated with dense
      area (some P(x) or P(c) <0.05). All associations were independent of menopausal
      status. At least two common breast cancer susceptibility variants are associated
      with mammographic density measures that predict breast cancer. These findings
      could help elucidate how those variants and mammographic density measures are
      associated with breast cancer susceptibility.

PMID- 20145139
TI  - Dendritic cell-derived exosomes for cancer immunotherapy: what's next?
AB  - Exosomes are nanovesicles originating from late endosomal compartments and
      secreted by most living cells in ex vivo cell culture conditions. The interest in
      exosomes was rekindled when B-cell and dendritic cell-derived exosomes were shown
      to mediate MHC-dependent immune responses. Despite limited understanding of
      exosome biogenesis and physiological relevance, accumulating evidence points to
      their bioactivity culminating in clinical applications in cancer. This review
      focuses on the preclinical studies exploiting the immunogenicity of dendritic
      cell-derived exosomes (Dex) and will elaborate on the past and future vaccination
      trials conducted using Dex strategy in melanoma and non-small cell lung cancer
      patients.

PMID- 20145140
TI  - Polo-like kinase 1 (Plk1) as a novel drug target in chronic myeloid leukemia:
      overriding imatinib resistance with the Plk1 inhibitor BI 2536.
AB  - In most patients with chronic myeloid leukemia (CML), the disease can be kept
      under control using the BCR/ABL kinase inhibitor imatinib. Nevertheless,
      resistance or intolerance to imatinib and other BCR/ABL inhibitors may occur
      during therapy. Therefore, CML research is focusing on novel targets and targeted
      drugs. Polo-like kinase 1 (Plk1) is a serine/threonine kinase that plays an
      essential role in mitosis. In this study, we examined the expression of Plk1 in
      CML cells and its potential role as a therapeutic target. Plk1 was found to be
      expressed in phosphorylated form in the CML cell line K562 as well as in primary
      CML cells in all patients tested. Inhibition of BCR/ABL by imatinib or nilotinib
      (AMN107) led to decreased expression of the Plk1 protein in CML cells, suggesting
      that BCR/ABL promotes Plk1 generation. Silencing of Plk1 in CML cells by a small
      interfering RNA approach was followed by cell cycle arrest and apoptosis.
      Furthermore, the Plk1-targeting drug BI 2536 was found to inhibit proliferation
      of imatinib-sensitive and imatinib-resistant CML cells, including leukemic cells,
      carrying the T315 mutation of BCR/ABL with reasonable IC(50) values (1-50
      nmol/L). The growth-inhibitory effects of BI 2536 on CML cells were found to be
      associated with cell cycle arrest and apoptosis. Moreover, BI 2536 was found to
      synergize with imatinib and nilotinib in producing growth inhibition in CML
      cells. In conclusion, Plk1 is expressed in CML cells and may represent a novel,
      interesting target in imatinib-sensitive and imatinib-resistant CML.

PMID- 20145141
TI  - General transcription factor binding at CpG islands in normal cells correlates
      with resistance to de novo DNA methylation in cancer cells.
AB  - Aberrant DNA methylation at CpG islands is thought to contribute to cancer
      initiation and progression, but mechanisms that establish and maintain DNA
      methylation status during tumorigenesis or normal development remain poorly
      understood. In this study, we used methyl-CpG immunoprecipitation to generate
      comparative DNA methylation profiles of healthy and malignant cells (acute
      leukemia and colorectal carcinoma) for human CpG islands across the genome. While
      searching for sequence patterns that characterize DNA methylation states, we
      discovered several nonredundant sequences in CpG islands that were resistant to
      aberrant de novo methylation in cancer and that resembled consensus binding sites
      for general transcription factors (TF). Comparing methylation profiles with
      global CpG island binding data for specific protein 1, nuclear respiratory factor
      1, and yin-yang 1 revealed that their DNA binding activity in normal blood cells
      correlated strictly with an absence of de novo methylation in cancer. In
      addition, global evidence showed that binding of any of these TFs to their
      consensus motif depended on their co-occurrence with neighboring consensus
      motifs. In summary, our results had two major implications. First, they pointed
      to a major role for cooperative binding of TFs in maintaining the unmethylated
      status of CpG islands in health and disease. Second, our results suggest that the
      majority of de novo methylated CpG islands are characterized by the lack of
      sequence motif combinations and the absence of activating TF binding.

PMID- 20145142
TI  - Comment re: Premenopausal mammographic density and hormone levels.

PMID- 20145144
TI  - Sensitivity and acquired resistance of BRCA1;p53-deficient mouse mammary tumors
      to the topoisomerase I inhibitor topotecan.
AB  - There is no tailored therapy yet for human basal-like mammary carcinomas.
      However, BRCA1 dysfunction is frequently present in these malignancies,
      compromising homology-directed DNA repair. This defect may serve as the tumor's
      Achilles heel and make the tumor hypersensitive to DNA breaks. We have evaluated
      this putative synthetic lethality in a genetically engineered mouse model for
      BRCA1-associated breast cancer, using the topoisomerase I (Top1) poison topotecan
      as monotherapy and in combination with poly(ADP-ribose) polymerase inhibition by
      olaparib. All 20 tumors tested were topotecan sensitive, but response
      heterogeneity was substantial. Although topotecan increased mouse survival, all
      tumors eventually acquired resistance. As mechanisms of in vivo resistance, we
      identified overexpression of Abcg2/Bcrp and markedly reduced protein levels of
      the drug target Top1 (without altered mRNA levels). Tumor-specific genetic
      ablation of Abcg2 significantly increased overall survival of topotecan-treated
      animals (P < 0.001), confirming the in vivo relevance of ABCG2 for topotecan
      resistance in a novel approach. Despite the lack of ABCG2, a putative tumor
      initiating cell marker, none of the 11 Abcg2(-/-);Brca1(-/-);p53(-/-) tumors were
      eradicated, not even by the combination topotecan-olaparib. We find that olaparib
      substantially increases topotecan toxicity in this model, and we suggest that
      this might also happen in humans.

PMID- 20145146
TI  - Comment re: Intratumoral immune reaction in human colorectal cancer.

PMID- 20145145
TI  - MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the
      activated c-Met receptor.
AB  - The receptor tyrosine kinase c-Met is an attractive target for therapeutic
      blockade in cancer. Here, we describe MK-2461, a novel ATP-competitive
      multitargeted inhibitor of activated c-Met. MK-2461 inhibited in vitro
      phosphorylation of a peptide substrate recognized by wild-type or oncogenic c-Met
      kinases (N1100Y, Y1230C, Y1230H, Y1235D, and M1250T) with IC(50) values of 0.4 to
      2.5 nmol/L. In contrast, MK-2461 was several hundredfold less potent as an
      inhibitor of c-Met autophosphorylation at the kinase activation loop. In tumor
      cells, MK-2461 effectively suppressed constitutive or ligand-induced
      phosphorylation of the juxtamembrane domain and COOH-terminal docking site of c
      Met, and its downstream signaling to the phosphoinositide 3-kinase-AKT and Ras
      extracellular signal-regulated kinase pathways, without inhibiting
      autophosphorylation of the c-Met activation loop. BIAcore studies indicated 6
      fold tighter binding to c-Met when it was phosphorylated, suggesting that MK-2461
      binds preferentially to activated c-Met. MK-2461 displayed significant inhibitory
      activities against fibroblast growth factor receptor (FGFR), platelet-derived
      growth factor receptor, and other receptor tyrosine kinases. In cell culture, MK
      2461 inhibited hepatocyte growth factor/c-Met-dependent mitogenesis, migration,
      cell scatter, and tubulogenesis. Seven of 10 MK-2461-sensitive tumor cell lines
      identified from a large panel harbored genomic amplification of MET or FGFR2. In
      a murine xenograft model of c-Met-dependent gastric cancer, a well-tolerated oral
      regimen of MK-2461 administered at 100 mg/kg twice daily effectively suppressed c
      Met signaling and tumor growth. Similarly, MK-2461 inhibited the growth of tumors
      formed by s.c. injection of mouse NIH-3T3 cells expressing oncogenic c-Met
      mutants. Taken together, our findings support further preclinical development of
      MK-2461 for cancer therapy.

PMID- 20145147
TI  - p53 is a direct transcriptional target of MYCN in neuroblastoma.
AB  - MYCN amplification occurs in approximately 25% of neuroblastomas, where it is
      associated with rapid tumor progression and poor prognosis. MYCN plays a
      paradoxical role in driving cellular proliferation and inducing apoptosis. Based
      on observations of nuclear p53 accumulation in neuroblastoma, we hypothesized
      that MYCN may regulate p53 in this setting. Immunohistochemical analysis of 82
      neuroblastoma tumors showed an association of high p53 expression with MYCN
      expression and amplification. In a panel of 5 MYCN-amplified and 5 nonamplified
      neuroblastoma cell lines, and also in the Tet21N-regulatable MYCN expression
      system, we further documented a correlation between the expression of MYCN and
      p53. In MYCN-amplified neuroblastoma cell lines, MYCN knockdown decreased p53
      expression. In Tet21N MYCN+ cells, higher levels of p53 transcription, mRNA, and
      protein were observed relative to Tet21N MYCN- cells. In chromatin
      immunoprecipitation and reporter gene assays, MYCN bound directly to a Myc E-Box
      DNA binding motif located close to the transcriptional start site within the p53
      promoter, where it could initiate transcription. E-Box mutation decreased MYCN
      driven transcriptional activation. Microarray analysis of Tet21N MYCN+/- cells
      identified several p53-regulated genes that were upregulated in the presence of
      MYCN, including MDM2 and PUMA, the levels of which were reduced by MYCN
      knockdown. We concluded that MYCN transcriptionally upregulates p53 in
      neuroblastoma and uses p53 to mediate a key mechanism of apoptosis.

PMID- 20145149
TI  - DNA methylation-dependent repression of PDZ-LIM domain-containing protein 2 in
      colon cancer and its role as a potential therapeutic target.
AB  - Constitutive activation of the nuclear factor-kappaB (NF-kappaB) transcription
      factor plays a key role in chronic colonic inflammation and colon tumorigenesis.
      However, the mechanisms by which the tightly regulated NF-kappaB pathway becomes
      constitutively activated during colonic pathogenesis remain obscure. Here, we
      report that PDLIM2, an essential terminator of NF-kappaB activation, is repressed
      in various human colorectal cancer cell lines, suggesting one important mechanism
      for the constitutive activation of NF-kappaB. Indeed, expression of exogenous
      PDLIM2 inhibited constitutive NF-kappaB activation in these colorectal cancer
      cells. Importantly, the PDLIM2 expression was sufficient to suppress in vitro
      anchorage-independent growth and in vivo tumor formation of these malignant
      cells. We have further shown that the PDLIM2 repression involves promoter
      methylation. Accordingly, treatment of the colorectal tumor cell lines with the
      DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine restored PDLIM2 expression
      and resulted in growth arrest. These studies thus provide new mechanistic
      insights into colon tumorigenesis by identifying a novel tumor suppressor role
      for PDLIM2.

PMID- 20145150
TI  - A placental growth factor variant unable to recognize vascular endothelial growth
      factor (VEGF) receptor-1 inhibits VEGF-dependent tumor angiogenesis via
      heterodimerization.
AB  - Angiogenesis is one of the crucial events for cancer development and growth. Two
      members of the vascular endothelial growth factor (VEGF) family, VEGF-A and
      placental growth factor (PlGF), which are able to heterodimerize if coexpressed
      in the same cell, are both required for pathologic angiogenesis. We have
      generated a PlGF1 variant, named PlGF1-DE in which the residues Asp72 and Glu73
      were substituted with Ala, which is unable to bind and activate VEGF receptor-1
      but is still able to heterodimerize with VEGF. Here, we show that overexpression
      in tumor cells by adenoviral delivery or stable transfection of PlGF1-DE variant
      significantly reduces the production of VEGF homodimer via heterodimerization,
      determining a strong inhibition of xenograft tumor growth and neoangiogenesis, as
      well as significant reduction of vessel lumen and stabilization, and monocyte
      macrophage infiltration. Conversely, the overexpression of PlGF1wt, also reducing
      the VEGF homodimer production comparably with PlGF1-DE variant through the
      generation of VEGF/PlGF heterodimer, does not inhibit tumor growth and vessel
      density compared with controls but induces increase of vessel lumen, vessel
      stabilization, and monocyte-macrophage infiltration. The property of PlGF and
      VEGF-A to generate heterodimer represents a successful strategy to inhibit VEGF
      dependent angiogenesis. The PlGF1-DE variant, and not PlGF1wt as previously
      reported, acts as a "dominant negative" of VEGF and is a new candidate for
      antiangiogenic gene therapy in cancer treatment.

PMID- 20145151
TI  - Nuclear Janus-activated kinase 2/nuclear factor 1-C2 suppresses tumorigenesis and
      epithelial-to-mesenchymal transition by repressing Forkhead box F1.
AB  - Progression to metastasis is the proximal cause of most cancer-related mortality.
      Yet much remains to be understood about what determines the spread of tumor
      cells. This paper describes a novel pathway in breast cancer that regulates
      epithelial-to-mesenchymal transition (EMT), motility, and invasiveness. We
      identify two transcription factors, nuclear factor 1-C2 (NF1-C2) and Forkhead box
      F1 (FoxF1), downstream of prolactin/nuclear Janus-activated kinase 2, with
      opposite effects on these processes. We show that NF1-C2 is lost during mammary
      tumor progression and is almost invariably absent from lymph node metastases. NF1
      C2 levels in primary tumors correlate with better patient survival. Manipulation
      of NF1-C2 levels by expression of a stabilized version or using small interfering
      RNA showed that NF1-C2 counteracts EMT, motility, invasiveness, and tumor growth.
      FoxF1 was found to be a direct repressed target of NF1-C2. We provide the first
      evidence for a role of FoxF1 in cancer and in the regulation of EMT in cells of
      epithelial origin. Overexpression of FoxF1 was associated with a mesenchymal
      phenotype, increased invasiveness in vitro, and enhanced growth of breast
      carcinoma xenografts in nude mice. The relevance of these findings is
      strengthened by the correlation between FoxF1 expression and a mesenchymal
      phenoype in breast cancer cell isolates, consistent with the interpretation that
      FoxF1 promotes invasion and metastasis.

PMID- 20145152
TI  - miR-181a and miR-630 regulate cisplatin-induced cancer cell death.
AB  - MicroRNAs (miRNA) are noncoding RNAs that regulate multiple cellular processes,
      including proliferation and apoptosis. We used microarray technology to identify
      miRNAs that were upregulated by non-small cell lung cancer (NSCLC) A549 cells in
      response to cisplatin (CDDP). The corresponding synthetic miRNA precursors (pre
      miRNAs) per se were not lethal when transfected into A549 cells yet affected cell
      death induction by CDDP, C2-ceramide, cadmium, etoposide, and mitoxantrone in an
      inducer-specific fashion. Whereas synthetic miRNA inhibitors (anti-miRNAs)
      targeting miR-181a and miR-630 failed to modulate the response of A549 to CDDP,
      pre-miR-181a and pre-miR-630 enhanced and reduced CDDP-triggered cell death,
      respectively. Pre-miR-181a and pre-miR-630 consistently modulated
      mitochondrial/postmitochondrial steps of the intrinsic pathway of apoptosis,
      including Bax oligomerization, mitochondrial transmembrane potential dissipation,
      and the proteolytic maturation of caspase-9 and caspase-3. In addition, pre-miR
      630 blocked early manifestations of the DNA damage response, including the
      phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and of two ATM
      substrates, histone H2AX and p53. Pharmacologic and genetic inhibition of p53
      corroborated the hypothesis that pre-miR-630 (but not pre-miR-181a) blocks the
      upstream signaling pathways that are ignited by DNA damage and converge on p53
      activation. Pre-miR-630 arrested A549 cells in the G0-G1 phase of the cell cycle,
      correlating with increased levels of the cell cycle inhibitor p27(Kip1) as well
      as with reduced proliferation rates and resulting in greatly diminished
      sensitivity of A549 cells to the late S-G2-M cell cycle arrest mediated by CDDP.
      Altogether, these results identify miR-181a and miR-630 as novel modulators of
      the CDDP response in NSCLC.

PMID- 20145153
TI  - Remote control of intestinal tumorigenesis by innate immunity.
AB  - Chronic intestinal inflammation has been linked to the development of colorectal
      cancer. Recent studies suggest that during chronic inflammation, the innate
      immune system may facilitate colon tumorigenesis in genetically predisposed
      individuals in response to certain indigenous microorganisms and/or cell
      remnants. In these individuals, therapeutic approaches that reroute the innate
      immune system's inflammatory and antimicrobial activities might help prevent
      colon tumorigenesis and metastasis.

PMID- 20145154
TI  - FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor
      growth.
AB  - Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family,
      and it has recently been proposed to participate in gastric acid secretion and
      mucin gene expression in mice. However, the role of FOXQ1 in humans and
      especially in cancer cells remains unknown. We found that FOXQ1 mRNA is
      overexpressed in clinical specimens of colorectal cancer (CRC; 28-fold/colonic
      mucosa). A microarray analysis revealed that the knockdown of FOXQ1 using small
      interfering RNA resulted in a decrease in p21(CIP1/WAF1) expression, and a
      reporter assay and a chromatin immunoprecipitation assay showed that p21 was one
      of the target genes of FOXQ1. Stable FOXQ1-overexpressing cells (H1299/FOXQ1)
      exhibited elevated levels of p21 expression and inhibition of apoptosis induced
      by doxorubicin or camptothecin. Although cellular proliferation was decreased in
      H1299/FOXQ1 cells in vitro, H1299/FOXQ1 cells significantly increased
      tumorigenicity [enhanced green fluorescent protein (EGFP): 2/15, FOXQ1: 7/15] and
      enhanced tumor growth (437 +/- 301 versus 1735 +/- 769 mm3, P < 0.001) in vivo.
      Meanwhile, stable p21 knockdown of H1299/FOXQ1 cells increased tumor growth,
      suggesting that FOXQ1 promotes tumor growth independent of p21. Microarray
      analysis of H1299/EGFP and H1299/FOXQ1 revealed that FOXQ1 overexpression
      upregulated several genes that have positive roles for tumor growth, including
      VEGFA, WNT3A, RSPO2, and BCL11A. CD31 and terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling staining of the tumor specimens showed that FOXQ1
      overexpression mediated the angiogenic and antiapoptotic effect in vivo. In
      conclusion, FOXQ1 is overexpressed in CRC and enhances tumorigenicity and tumor
      growth presumably through its angiogenic and antiapoptotic effects. Our findings
      show that FOXQ1 is a new member of the cancer-related FOX family.

PMID- 20145155
TI  - Transcriptional profiles of CD133+ and CD133- glioblastoma-derived cancer stem
      cell lines suggest different cells of origin.
AB  - Glioblastoma multiforme (GBM) is paradigmatic for the investigation of cancer
      stem cells (CSC) in solid tumors. Growing evidence suggests that different types
      of CSC lead to the formation of GBM. This has prompted the present comparison of
      gene expression profiles between 17 GBM CSC lines and their different putative
      founder cells. Using a newly derived 24-gene signature, we can now distinguish
      two subgroups of GBM: Type I CSC lines display "proneural" signature genes and
      resemble fetal neural stem cell (fNSC) lines, whereas type II CSC lines show
      "mesenchymal" transcriptional profiles similar to adult NSC (aNSC) lines.
      Phenotypically, type I CSC lines are CD133 positive and grow as neurospheres.
      Type II CSC lines, in contrast, display (semi-)adherent growth and lack CD133
      expression. Molecular differences between type I and type II CSC lines include
      the expression of extracellular matrix molecules and the transcriptional activity
      of the WNT and the transforming growth factor-beta/bone morphogenetic protein
      signaling pathways. Importantly, these characteristics were not affected by
      induced adherence on laminin. Comparing CSC lines with their putative cells of
      origin, we observed greatly increased proliferation and impaired differentiation
      capacity in both types of CSC lines but no cancer-associated activation of
      otherwise silent signaling pathways. Thus, our data suggest that the
      heterogeneous tumor entity GBM may derive from cells that have preserved or
      acquired properties of either fNSC or aNSC but lost the corresponding
      differentiation potential. Moreover, we propose a gene signature that enables the
      subclassification of GBM according to their putative cells of origin.

PMID- 20145156
TI  - A 3'-untranslated region polymorphism in IGF1 predicts survival of non-small cell
      lung cancer in a Chinese population.
AB  - PURPOSE: Disruption of the balance of insulin-like growth factor I (IGF-I) and
      IGF-binding protein 3 (IGFBP3) has been implicated in the etiology and
      progression of lung and other cancers. Single nucleotide polymorphisms (SNP) in
      IGF1 and IGFBP3 have been reported to be associated with the expression of the
      IGF-I/IGFBP3 axis. Therefore, we hypothesized that SNPs in these two genes were
      associated with lung cancer survival. EXPERIMENTAL DESIGN: We selected and
      genotyped 21 tagging and potentially functional SNPs in IGF1 and IGFBP3 by using
      Illumina Goldengate Genotyping Chip in a case cohort of 568 patients diagnosed
      with non-small cell lung cancer (NSCLC) in a Chinese population. Log-rank test
      and Cox proportional hazard models were used for the survival analyses. RESULTS:
      We found that rs5742714C/G in the 3'-untranslated region of IGF1 was associated
      significantly with NSCLC survival after adjustment for demographic and
      clinicopathologic factors, showing an improved median survival time in patients
      carrying variant CG/GG genotypes [median survival time, 28.5 months for CG/GG and
      23.0 for CC; crude hazard ratio (HR), 0.74; 95% confidence interval (95% CI),
      0.57-0.95, and adjusted HR, 0.77; 95% CI, 0.60-0.99]. This protective effect was
      more predominant for patients receiving surgical operation (HR, 0.58; 95% CI,
      0.40-0.85; P for heterogeneity test = 0.045), along with a significant
      multiplicative interaction between variant genotypes and operation status (P =
      0.028). CONCLUSIONS: Our findings suggest that rs5742714 in IGF1 may be a genetic
      modifier for NSCLC prognosis in this Chinese population, especially among
      patients with surgical operation.

PMID- 20145158
TI  - Targeting the cytoprotective chaperone, clusterin, for treatment of advanced
      cancer.
AB  - Many strategies used to kill cancer cells induce stress-responses that activate
      survival pathways to promote emergence of a treatment resistant phenotype.
      Secretory clusterin (sCLU) is a stress-activated cytoprotective chaperone up
      regulated by many varied anticancer therapies to confer treatment resistance when
      overexpressed. sCLU levels are increased in several treatment recurrent cancers
      including castrate resistant prostate cancer, and therefore sCLU has become an
      attractive target in cancer therapy. sCLU is not druggable with small molecule
      inhibitors, therefore nucleotide-based strategies to inhibit sCLU at the RNA
      level are appealing. Preclinical studies have shown that antisense
      oligonucleotide (ASO) or siRNA knockdown of sCLU have preclinical activity in
      combination with hormone- and chemotherapy. Phase I and II clinical trial data
      indicate that the second generation ASO, custirsen (OGX-011), has biologic and
      clinical activity, suppressing sCLU expression in prostate cancer tissues by more
      than 90%. A randomized study comparing docetaxel-custirsen to docetaxel alone in
      men with castrate resistant prostate cancer reported improved survival by 7
      months from 16.9 to 23.8 months. Strong preclinical and clinical proof-of
      principle data provide rationale for further study of sCLU inhibitors in
      randomized phase III trials, which are planned to begin in 2010.

PMID- 20145159
TI  - Potential clinical significance of a plasma-based KRAS mutation analysis in
      patients with advanced non-small cell lung cancer.
AB  - PURPOSE: Non-small cell lung cancer (NSCLC) with KRAS mutation may be resistant
      to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This
      study aims to evaluate a plasma-based KRAS mutation analysis and the clinical
      significance of plasma KRAS mutation as a predictive marker for tumor resistance
      to EGFR-TKIs in patients with NSCLC. EXPERIMENTAL DESIGN: DNA extracted from
      plasma and matched tumor tissues were obtained from 273 patients with advanced
      stage NSCLC. Patients were followed up prospectively for treatment outcomes. KRAS
      mutations in codon 12 and 13 were detected using PCR-restriction fragment length
      polymorphism. Mutations in plasma and matched tumors were compared. Associations
      between KRAS mutation status and patients' clinical outcomes were analyzed.
      RESULTS: KRAS mutation was found in 35 (12.8%) plasma samples and 30 (11.0%)
      matched tumor tissues. The consistency of KRAS mutations between plasma and
      tumors is 76.7% (23 of 30; kappa = 0.668; P < 0.001). Among 120 patients who
      received EGFR-TKI treatment, the response rate was only 5.3% (1 of 19) for
      patients with plasma KRAS mutation compared with 29.7% for patients with no KRAS
      mutation in plasma DNA (P = 0.024). The median progression-free survival time of
      patients with plasma KRAS mutation was 2.5 months compared with 8.8 months for
      patients with wild-type KRAS (P < 0.001). CONCLUSIONS: KRAS mutation in plasma
      DNA correlates with the mutation status in the matched tumor tissues of patients
      with NSCLC. Plasma KRAS mutation status is associated with a poor tumor response
      to EGFR-TKIs in NSCLC patients and may be used as a predictive marker in
      selecting patients for such treatment.

PMID- 20145160
TI  - Low levels of phosphorylated epidermal growth factor receptor in nonmalignant and
      malignant prostate tissue predict favorable outcome in prostate cancer patients.
AB  - PURPOSE: To explore if the expression of phosphorylated epidermal growth factor
      receptor (pEGFR) in nonmalignant and malignant prostate tissue is a potential
      prognostic marker for outcome in prostate cancer patients. EXPERIMENTAL DESIGN:
      We used formalin-fixed tissues obtained through the transurethral resection of
      the prostate from 259 patients diagnosed with prostate cancer after the
      transurethral resection of the prostate, and patients were then followed with
      watchful waiting. Tissue microarrays of nonmalignant and malignant prostate
      tissue were stained with an antibody against pEGFR. The staining pattern was
      scored and related to clinicopathologic parameters and to outcome. RESULTS: Low
      phosphorylation of EGFR in prostate epithelial cells, both in the tumor and
      surprisingly also in the surrounding nonmalignant tissue, was associated with
      significantly longer cancer-specific survival in prostate cancer patients. This
      association remained significant when Gleason score and local tumor stage were
      added together with pEGFR to a Cox regression model. Tumor epithelial pEGFR
      immunoreactivity was significantly correlated to tumor cell proliferation, tumor
      vascular density, and nonmalignant epithelial pEGFR immunoreactivity. Patients
      with metastases had significantly higher immunoreactivity for tumor and
      nonmalignant epithelial pEGFR compared with patients without metastases.
      CONCLUSIONS: Low pEGFR immunoreactivity is associated with the favorable
      prognosis in prostate cancer patients and may provide information about which
      patients with Gleason score 6 and 7 tumors that will survive their disease even
      without treatment. Changes in the nonmalignant tissue adjacent to prostate tumors
      give prognostic information.

PMID- 20145162
TI  - The predictive value of HLA class I tumor cell expression and presence of
      intratumoral Tregs for chemotherapy in patients with early breast cancer.
AB  - PURPOSE: We hypothesized that T-cell immune interaction affects tumor development
      and thus clinical outcome. Therefore, we examined the clinical impact of human
      leukocyte antigen (HLA) class I tumor cell expression and regulatory T-cell
      (Treg) infiltration in breast cancer. EXPERIMENTAL DESIGN: Our study population
      (N = 677) is consisted of all early breast cancer patients primarily treated with
      surgery in our center between 1985 and 1994. Formalin-fixed, paraffin-embedded
      tumor tissue was immunohistochemically stained using HCA2, HC10, and Foxp3
      monoclonal antibodies. RESULTS: HLA class I expression was evaluated by combining
      results from HCA2 and HC10 antibodies and classified into three groups: loss,
      downregulation, and expression. Remarkably, only in patients who received
      chemotherapy, both presence of Treg (P = 0.013) and higher HLA class I expression
      levels (P = 0.002) resulted in less relapses, independently of other variables.
      Treg and HLA class I were not of influence on clinical outcome in patients who
      did not receive chemotherapy. CONCLUSIONS: We showed that HLA class I and Treg
      affect prognosis exclusively in chemotherapy-treated patients and are therefore
      one of the few predictive factors for chemotherapy response in early breast
      cancer patients. Chemotherapy may selectively eliminate Treg, thus enabling CTLs
      to kill tumor cells that have retained HLA class I expression. As a consequence,
      HLA class I and Treg can predict response to chemotherapy with high
      discriminative power. These markers could be applied in response prediction to
      chemotherapy in breast cancer patients.

PMID- 20145161
TI  - Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients
      related to increased risk of distant metastases and tumor recurrence.
AB  - PURPOSE: The goal of this study was to examine the effect of tobacco use on
      disease recurrence (local/regional recurrence, distant metastasis, or second
      primary) among patients with human papillomavirus (HPV)-positive squamous cell
      carcinoma of the oropharynx (SCCOP) following a complete response to
      chemoradiation therapy. EXPERIMENTAL DESIGN: Between 1999 and 2007, 124 patients
      with advanced SCCOP (86% with stage IV) and adequate tumor tissue for HPV
      analysis who were enrolled in one of two consecutive University of Michigan
      treatment protocols were prospectively included in this study. Patients were
      categorized as never-, former, or current tobacco users. The primary end points
      were risk of disease recurrence and time to recurrence; secondary end points were
      disease-specific survival and overall survival. RESULTS: One hundred and two
      patients (82.3%) had HPV-positive tumors. Over two thirds (68%) of patients with
      HPV-positive tumors were tobacco users. Among HPV-positive patients, current
      tobacco users were at significantly higher risk of disease recurrence than never
      tobacco users (hazard ratio, 5.2; confidence interval, 1.1-24.4; P = 0.038).
      Thirty-five percent of HPV-positive ever tobacco users recurred compared with
      only 6% of HPV-positive never users and 50% of HPV-negative patients. All HPV
      negative patients were tobacco users and had significantly shorter times to
      recurrence (P = 0.002), and had reduced disease-specific survival (P = 0.004) and
      overall survival (P < 0.001) compared with HPV-positive patients. Compared with
      HPV-positive never-tobacco users, those with a tobacco history showed a trend for
      reduced disease-specific survival (P = 0.064) but not overall survival (P =
      0.221). CONCLUSIONS: Current tobacco users with advanced, HPV-positive SCCOP are
      at higher risk of disease recurrence compared with never-tobacco users.

PMID- 20145163
TI  - X-linked ectodermal dysplasia receptor is downregulated in breast cancer via
      promoter methylation.
AB  - PURPOSE: The X-linked ectodermal dysplasia receptor (XEDAR) is a novel receptor
      of the tumor necrosis factor receptor family that binds to ectodysplasin-A2 (EDA
      A2) and induces cell death. The purpose of this study was to determine the tumor
      suppressive potential of XEDAR in the development of breast cancer. EXPERIMENTAL
      DESIGN: We analyzed the expression of XEDAR in breast cancer cell lines and tumor
      samples using quantitative real-time PCR analysis and immunoblotting. We analyzed
      the human XEDAR gene promoter for the presence of any CpG island and examined its
      methylation status using methylation-specific real-time PCR. We examined the
      effect of 5-aza-2'-deoxycytidine on the expression of XEDAR and sensitivity to
      EDA-A2-induced apoptosis in breast cancer cell lines. RESULTS: Expression of
      XEDAR, but not EDA-A2, was downregulated in most tumorigenic breast cancer cell
      lines and tumor samples. Loss of XEDAR expression correlated with the
      hypermethylation of its promoter. Ectopic expression of XEDAR in MDA-MB-231 cells
      resulted in significant induction of apoptosis and reduction in colony formation.
      Treatment with 5-aza-2'-deoxycytidine restored XEDAR expression in breast cancer
      cell lines with methylated XEDAR promoter and sensitized them to EDA-A2-induced
      cell death. CONCLUSIONS: Our results suggest that XEDAR expression is
      downregulated in most breast cancers via promoter methylation, which may
      contribute to accelerated tumor development by blocking EDA-A2-induced cell
      death. XEDAR may represent a novel breast tumor suppressor gene, and restoration
      of its expression by treatment with DNA demethylating agents may represent an
      attractive approach for the treatment of breast cancer.

PMID- 20145164
TI  - Studies of TMPRSS2-ERG gene fusions in diagnostic trans-rectal prostate biopsies.

PMID- 20145166
TI  - Randomized Phase III trial of gefitinib versus docetaxel in non-small cell lung
      cancer patients who have previously received platinum-based chemotherapy.
AB  - PURPOSE: The ISTANA (IRESSA as Second-line Therapy in Advanced NSCLC-KoreA) study
      compared gefitinib with docetaxel in patients with advanced or metastatic non
      small cell lung carcinoma (NSCLC) pretreated with platinum-based chemotherapy.
      EXPERIMENTAL DESIGN: We conducted a multicenter, randomized, open-label phase III
      trial of gefitinib (250 mg/d) versus docetaxel (75 mg/m(2) day 1 every 3 weeks)
      in patients with advanced or metastatic NSCLC treated with one previous platinum
      based chemotherapy. The primary endpoint was progression-free survival. RESULTS:
      A total of 161 patients (male, 62%; never smoker, 41%; adenocarcinoma, 68%) were
      enrolled. Progression-free survival was longer for gefitinib compared with
      docetaxel (hazard ratio, 0.729; 90% confidence interval, 0.533-0.998; one-sided P
      = 0.0441). Gefitinib significantly improved objective response rate (28.1% versus
      7.6%; two-sided P = 0.0007). In the final analysis of overall survival, the
      hazard ratio was 0.870 (95% confidence interval, 0.613-1.236; two-sided P =
      0.4370). No significant differences were seen in the quality of life or symptom
      improvement rates between the two treatment groups. Gefitinib was well tolerated,
      was consistent with previous data and disease, and had fewer serious adverse
      events and fewer Common Terminology Criteria for Adverse Events grade 3 or 4
      adverse events than docetaxel. The incidence of interstitial lung disease-type
      events was 3.7% (n = 3) with gefitinib and 3.9% (n = 3) with docetaxel.
      CONCLUSIONS: The primary endpoint of progression-free survival was longer with
      gefitinib than docetaxel, and the secondary endpoints showed superior objective
      response rate, good tolerability, and similar quality of life improvement rates
      for gefitinib than docetaxel. Therefore, gefitinib is an important valid
      treatment option for second-line therapy for Korean NSCLC patients.

PMID- 20145167
TI  - Dasatinib inhibits the growth of molecularly heterogeneous myeloid leukemias.
AB  - PURPOSE: Dasatinib is a dual Src/Abl inhibitor recently approved for Bcr-Abl+
      leukemias with resistance or intolerance to prior therapy. Because Src kinases
      contribute to multiple blood cell functions by triggering a variety of signaling
      pathways, we hypothesized that their molecular targeting might lead to growth
      inhibition in acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: We studied
      growth factor-dependent and growth factor-independent leukemic cell lines,
      including three cell lines expressing mutants of receptor tyrosine kinases (Flt3
      or c-Kit) as well as primary AML blasts for responsiveness to dasatinib. RESULTS:
      Dasatinib resulted in the inhibition of Src family kinases in all cell lines and
      blast cells at approximately 1 x 10(-9) mol/L. It also inhibited mutant Flt3 or
      Kit tyrosine phosphorylation at approximately 1 x 10(-6) mol/L. Mo7e cells
      expressing the activating mutation (codon 816) of c-Kit were most sensitive to
      growth inhibition with a GI(50) of 5 x 10(-9) mol/L. Primary AML blast cells
      exhibited a growth inhibition of <1 x 10(-6) mol/L. Cell lines that showed growth
      inhibition at approximately 1 x 10(-6) mol/L showed a G(1) cell cycle arrest and
      correlated with accumulation of p21 and p27 protein. The addition of rapamycin or
      cytotoxic agents enhanced growth inhibition. Dasatinib also caused the apoptosis
      of Mo7e cells expressing oncogenic Kit. CONCLUSIONS: Although all of the precise
      targets for dasatinib are not known, this multikinase inhibitor causes either
      growth arrest or apoptosis in molecularly heterogeneous AML. The addition of
      cytotoxic or targeted agents can enhance its effects.

PMID- 20145168
TI  - Phase I clinical and magnetic resonance imaging study of the vascular agent NGR
      hTNF in patients with advanced cancers (European Organization for Research and
      Treatment of Cancer Study 16041).
AB  - PURPOSE: This phase I trial investigating the vascular targeting agent NGR-hTNF
      aimed to determine the (a) dose-limiting toxicities, (b) maximum tolerated dose
      (MTD), (c) pharmacokinetics and pharmacodynamics, (d) vascular response by
      dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and (e)
      preliminary clinical activity in solid tumors. EXPERIMENTAL DESIGN: NGR-hTNF was
      administered once every 3 weeks by a 20- to 60-minute i.v. infusion to cohorts of
      three to six patients with solid tumors in escalating doses. Pharmacokinetic and
      pharmacodynamic analyses in blood were done during the first four cycles. DCE-MRI
      was done in cycle 1 at baseline and 2 hours after the start of the infusion.
      RESULTS: Sixty-nine patients received a total of 201 cycles of NGR-hTNF (0.2-60
      microg/m(2)). Rigors and fever were the most frequently observed toxicities. Four
      dose-limiting toxicities were observed (at doses of 1.3, 8.1, and 60
      microg/m(2)), of which three were infusion related. The MTD was 45 microg/m(2).
      The mean apparent terminal half-life ranged from 0.963 to 2.08 hours. DCE-MRI
      results of tumors showed a vascular response to NGR-hTNF. No objective responses
      were observed, but 27 patients showed stable disease with a median duration of 12
      weeks. CONCLUSIONS: NGR-hTNF was well tolerated. The MTD was 45 microg/m(2)
      administered in 1 hour once every 3 weeks. DCE-MRI results showed the
      antivascular effect of NGR-hTNF. These findings call for further research for
      defining the optimal biological dose and clinical activity of NGR-hTNF as a
      single agent or in combination with cytotoxic drugs.

PMID- 20145169
TI  - Targeting the RB-pathway in cancer therapy.
AB  - The RB-pathway, consisting of inhibitors and activators of cyclin-dependent
      kinases, the retinoblastoma tumor suppressor (RB), and the E2F-family of
      transcription factors, plays critical roles in the regulation of cell cycle
      progression and cell death. Components of this pathway, particularly p16Ink4a,
      cyclin D1, and RB, are frequently altered in sporadic human cancers to promote
      deregulated cellular proliferation. The consistent disruption of the RB-pathway
      in human cancers raises the possibility of exploiting tumor-specific RB-pathway
      defects to improve the efficacy of current therapies and to develop new
      therapeutic strategies. This article discusses how the RB-pathway status impacts
      the cellular responses to cytotoxic, cytostatic, and hormone therapies, and how
      the components of the RB-pathway may be directly targeted to treat cancer.

PMID- 20145170
TI  - Smoking and colorectal cancer in Lynch syndrome: results from the Colon Cancer
      Family Registry and the University of Texas M.D. Anderson Cancer Center.
AB  - PURPOSE: Lynch syndrome family members with inherited germline mutations in DNA
      mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), and
      cases typically have tumors that exhibit a high level of microsatellite
      instability (MSI). There is some evidence that smoking is a risk factor for CRCs
      with high MSI; however, the association of smoking with CRC among those with
      Lynch syndrome is unknown. EXPERIMENTAL DESIGN: A multicentered retrospective
      cohort of 752 carriers of pathogenic MMR gene mutations was analyzed, using a
      weighted Cox regression analysis, adjusting for sex, ascertainment source, the
      specific mutated gene, year of birth, and familial clustering. RESULTS: Compared
      with never smokers, current smokers had a significantly increased CRC risk
      [adjusted hazard ratio (HR), 1.62; 95% confidence interval (95% CI), 1.01-2.57]
      and former smokers who had quit smoking for 2 or more years were at decreased
      risk (HR, 0.53; 95% CI, 0.35-0.82). CRC risk did not vary according to age at
      starting. However, light smoking (<10 cigarettes per day) and shorter duration of
      smoking (<10 years) were associated with decreased CRC risk (HR, 0.51; 95% CI,
      0.29-0.91 and HR, 0.52; 95% CI, 0.30-0.89, respectively). For former smokers, CRC
      risk decreased with years since quitting (P trend <0.01). CONCLUSIONS: People
      with Lynch syndrome may be at increased risk of CRC if they smoke regularly.
      Although our data suggest that former smokers, short-term smokers, and light
      smokers are at decreased CRC risk, these findings need further confirmation,
      preferably using prospective designs.

PMID- 20145171
TI  - Low-molecular-weight cyclin E can bypass letrozole-induced G1 arrest in human
      breast cancer cells and tumors.
AB  - PURPOSE: Low-molecular-weight cyclin E (LMW-E) in breast cancer cells induces
      genomic instability and resistance to inhibition by p21, p27, and fulvestrant
      therapy. Here, we sought to determine if LMW-E renders breast cancer cells
      unresponsive to aromatase inhibitors (AI), elucidate the mechanism of such
      resistance, and ascertain if inhibitors of LMW-E-associated kinase activity could
      overcome this resistance. EXPERIMENTAL DESIGN: The antiproliferative effects of
      the AIs were examined in aromatase-overexpressing MCF-7/Ac1 cells in the presence
      or absence of full-length cyclin E and LMW-E. Inhibition of LMW cyclin E kinase
      activity by roscovitine [a cyclin-dependent kinase (CDK) inhibitor] was examined
      in letrozole-unresponsive MCF-7/Ac1 cells. The role of LMW-E and CDK2 in
      mediating recurrence following AI treatment was also assessed in breast cancer
      patients. RESULTS: Overexpression of LMW-E in postmenopausal patients was
      associated with a poor prognosis. Letrozole, but not exemestane or anastrozole,
      mediated a pronounced G(1) arrest in MCF-7/Ac1 cells. Androstenedione-induced
      G(1) exit correlated with increased cyclin E-associated kinase activity and
      increased CDK2 levels. Letrozole treatment inhibited cyclin E-CDK2 kinase
      activity by preventing the androstenedione-induced increase in CDK2. LMW-E
      bypassed this effect and rendered the cells resistant to letrozole inhibition.
      Roscovitine blocked the androstenedione-induced increase in CDK2, and LMW-E
      overexpression could not bypass this effect. Lastly, breast cancer patients whose
      tumors overexpress LMW-E were not responsive to AI treatment. CONCLUSIONS:
      Roscovitine treatment can reverse intrinsic or acquired resistance to letrozole
      due to LMW-E expression in breast cancer cells. These data support the clinical
      investigation of CDK2 inhibitor therapy for postmenopausal women with estrogen
      receptor-positive, LMW-E-expressing breast cancer.

PMID- 20145172
TI  - Frequent downregulation of miR-34 family in human ovarian cancers.
AB  - PURPOSE: The miR-34 family is directly transactivated by tumor suppressor p53,
      which is frequently mutated in human epithelial ovarian cancer (EOC). We
      hypothesized that miR-34 expression would be decreased in EOC and that
      reconstituted miR-34 expression might reduce cell proliferation and invasion of
      EOC cells. EXPERIMENTAL DESIGNS: miR-34 expression was determined by quantitative
      reverse transcription-PCR and in situ hybridization in a panel of 83 human EOC
      samples. Functional characterization of miR-34 was accomplished by reconstitution
      of miR-34 expression in EOC cells with synthetic pre-miR molecules followed by
      determining changes in proliferation, apoptosis, and invasion. RESULTS: miR-34a
      expression is decreased in 100%, and miR-34b*/c in 72%, of EOC with p53 mutation,
      whereas miR-34a is also downregulated in 93% of tumors with wild-type p53.
      Furthermore, expression of miR-34b*/c is significantly reduced in stage IV tumors
      compared with stage III (P = 0.0171 and P = 0.0029, respectively). Additionally,
      we observed promoter methylation and copy number variations at mir-34. In situ
      hybridization showed that miR-34a expression is inversely correlated with MET
      immunohistochemical staining, consistent with translational inhibition by miR
      34a. Finally, miR-34 reconstitution experiments in p53 mutant EOC cells resulted
      in reduced proliferation, motility, and invasion, the latter of which was
      dependent on MET expression. CONCLUSIONS: Our work suggests that miR-34 family
      plays an important role in EOC pathogenesis and reduced expression of miR-34b*/c
      may be particularly important for progression to the most advanced stages. Part
      of miR-34 effects on motility and invasion may be explained by regulation of MET,
      which is frequently overexpressed in EOC.

PMID- 20145173
TI  - Blockade of the extracellular signal-regulated kinase pathway enhances the
      therapeutic efficacy of microtubule-destabilizing agents in human tumor xenograft
      models.
AB  - PURPOSE: The extracellular signal-regulated kinase (ERK) pathway is upregulated
      in human cancers and represents a target for mechanism-based approaches to cancer
      treatment. However, specific blockade of the ERK pathway alone induces mostly
      cytostatic rather than proapoptotic effects, resulting in a limited therapeutic
      efficacy of inhibitors that target the mitogen-activated protein kinase/ERK
      kinase (MEK). Given the cytoprotective role of the ERK pathway, we examined
      whether its blockade by the MEK inhibitor PD184352 might enhance the therapeutic
      efficacy of anticancer drugs in human tumor xenograft models. EXPERIMENTAL
      DESIGN: We recently showed that blockade of the ERK pathway by MEK inhibitors
      enhances the induction of apoptosis by microtubule-destabilizing agents,
      including TZT-1027 and vinorelbine, in various tumor cells with aberrant
      activation of the ERK pathway in vitro. We here examined the therapeutic efficacy
      of the combination of PD184352 with TZT-1027 or vinorelbine in nude mice
      harboring HT-29 or HT1080 tumor xenografts, in which the ERK pathway is activated
      as a result of mutations of BRAF and NRAS, respectively. RESULTS:
      Coadministration of PD184352 markedly sensitized HT-29 or HT1080 tumor xenografts
      to TZT-1027-induced or vinorelbine-induced cytotoxicity. Low doses of TZT-1027 or
      vinorelbine that by themselves showed little or moderate cytotoxicity thus
      suppressed the growth of HT-29 xenografts almost completely and induced
      essentially complete regression of HT1080 xenografts when administered with
      PD184352. The enhanced therapeutic efficacy of the drug combinations was achieved
      by a relatively transient blockade of the ERK pathway. CONCLUSIONS:
      Administration of both a MEK inhibitor and a microtubule-destabilizing agent
      represents a promising chemotherapeutic strategy with improved safety for cancer
      patients.

PMID- 20145174
TI  - Metastatic renal cell carcinoma treated with sunitinib: early evaluation of
      treatment response using dynamic contrast-enhanced ultrasonography.
AB  - PURPOSE: To determine the utility of dynamic contrast-enhanced ultrasonography
      (DCE-US) as a prognostic tool for metastatic renal cell carcinoma patients
      receiving sunitinib and to identify DCE-US parameters that correlate with early
      treatment response. EXPERIMENTAL DESIGN: Thirty-eight patients received 50 mg/d
      sunitinib on schedule 4/2 (4 weeks on followed by 2 weeks off treatment). After
      two cycles, response evaluation criteria in solid tumors were used to classify
      patients as responders or nonresponders. DCE-US evaluations were done before
      treatment and at day 15; variations between days 0 and 15 were calculated for
      seven DCE-US functional parameters and were compared for responders and
      nonresponders. The correlation between DCE-US parameters and disease-free
      survival (DFS) and overall survival (OS) was assessed. RESULTS: The ratio between
      DCE-US examinations at baseline and day 15 significantly correlated with response
      in five of the seven DCE-US parameters. Two DCE-US parameters (time to peak
      intensity and slope of the wash-in) were significantly associated with DFS; time
      to peak intensity was also significantly associated with OS. CONCLUSIONS: DCE-US
      is a useful tool for predicting the early efficacy of sunitinib in metastatic
      renal cell carcinoma patients. Robust correlations were observed between
      functional parameters and classic assessments, including DFS and OS.

PMID- 20145175
TI  - Vascular endothelial growth factor concentration as a predictive marker: ready
      for primetime?

PMID- 20145176
TI  - Chromosome 17 polysomy without human epidermal growth factor receptor 2
      amplification does not predict response to lapatinib plus paclitaxel compared
      with paclitaxel in metastatic breast cancer.
AB  - PURPOSE: It has been suggested that a subgroup of human epidermal growth factor
      receptor 2 (HER2)-negative breast cancer patients with chromosome 17 (Chr-17)
      polysomy benefit from HER2-directed therapy. This hypothesis was examined using
      the data from a phase III trial that randomized patients with HER2-negative or
      HER2-untested metastatic breast cancer to first-line therapy with paclitaxel
      along with either lapatinib or placebo. EXPERIMENTAL DESIGN: HER2 expression
      level by immunohistochemistry, fluorescence in situ hybridization (FISH), and
      mean HER2 ratio of Chr-17 values were determined centrally using archival tissue.
      Polysomy means of 2.0 and 2.2 served as thresholds. RESULTS: Of 580 patients on
      the original trial, 406 were HER2 negative by FISH. Progression-free survival
      (PFS) data were available for 405 patients, of whom 44 (11%) met the definition
      of polysomy (Chr-17 >or=2.2, FISH negative for HER2). Median PFS in the polysomy
      group was 20.9 and 24.4 weeks for paclitaxel plus lapatinib and paclitaxel plus
      placebo, respectively. In the nonpolysomy group, median PFS was 24.6 and 23.1
      weeks for paclitaxel plus lapatinib and paclitaxel plus placebo, respectively.
      Log-rank testing showed no treatment advantage for either group. Similar results
      were found using a Chr-17 polysomy cutoff of 2.0. Response rates in the polysomy
      group were 17% for paclitaxel plus lapatinib and 10% for paclitaxel plus placebo.
      In the nonpolysomy group, response rates were 32% for paclitaxel plus lapatinib
      and 25% for paclitaxel plus placebo. Neither comparison was statistically
      significant. CONCLUSION: This analysis could not confirm the hypothesis that Chr
      17 polysomy in HER2-nonamplified patients improved chemotherapy outcome when
      lapatinib is added as a HER2-targeted treatment.

PMID- 20145178
TI  - MutS homologue 2 and the long-term benefit of adjuvant chemotherapy in lung
      cancer.
AB  - PURPOSE: We sought to determine the long-term (median follow-up, 7.5 years)
      predictive power of human MutS homologue 2 (MSH2) immunohistochemical expression
      in patients who enrolled in the International Adjuvant Lung Trial. EXPERIMENTAL
      DESIGN: We tested the interaction between MSH2 and the allocated treatment
      (chemotherapy versus observation) in a Cox model adjusted on clinicopathologic
      variables. The significance level was set at 0.01. RESULTS: MSH2 levels were low
      in 257 (38%) and high in 416 (62%) tumors. The benefit from chemotherapy was
      likely different according to MSH2 (interaction test, P = 0.06): there was a
      trend for chemotherapy to prolong overall survival when MSH2 was low [hazard
      ratio (HR), 0.76; 95% confidence interval (95% CI), 0.59-0.97; P = 0.03], but not
      when MSH2 was high (HR, 1.12; 95% CI, 0.81-1.55; P = 0.48). In the control arm,
      the HR was 0.66 (95% CI, 0.49-0.90; P = 0.01) when MSH2 was high. When combining
      MSH2 with excision repair cross-complementing group 1 (ERCC1) into four
      subgroups, the benefit of chemotherapy decreased with the number of markers
      expressed at high levels (P = 0.01). A similar decrease was noted when combining
      MSH2 and P27 (P = 0.01). Chemotherapy prolonged overall survival in the combined
      low MSH2/low ERCC1 subgroup (HR, 0.65; 95% CI, 0.47-0.91; P = 0.01) and in the
      combined low MSH2/low P27 subgroup (HR, 0.65; 95% CI, 0.46-0.93; P = 0.01).
      CONCLUSIONS: MSH2 expression is a borderline significant predictor of a long-term
      benefit from adjuvant cisplatin-based chemotherapy in patients with completely
      resected lung cancer. MSH2 combined with ERCC1 or P27 may identify patients most
      likely to benefit durably from chemotherapy.

PMID- 20145177
TI  - A new therapy paradigm for prostate cancer founded on clinical observations.
AB  - Efficacy equivalent to that reported in other common adult solid tumors
      considered to be chemotherapy-sensitive has been reported with Docetaxel in
      patients with castrate-resistant prostate cancer. However, in contrast to other
      cancers, the expected increase in efficacy with the use of chemotherapy in
      earlier disease states has not been reported to date in prostate cancer. On the
      basis of these observations, we speculated that the therapy development paradigm
      used successfully in other cancers may not apply to the majority of prostate
      cancers. Several lines of supporting clinical and experimental observations
      implicate the tumor microenvironment in prostate carcinogenesis and resistance to
      therapy. We conclude that a foundation to guide the development of therapy for
      prostate cancer is required. The therapy paradigm we propose accounts for the
      central role of the tumor microenvironment in bone and, if correct, will lead to
      microenvironment-targeted therapy.

PMID- 20145179
TI  - Anti-transforming growth factor beta receptor II antibody has therapeutic
      efficacy against primary tumor growth and metastasis through multieffects on
      cancer, stroma, and immune cells.
AB  - PURPOSE: Transforming growth factor beta (TGFbeta) is a pleiotropic cytokine that
      affects tumor growth, metastasis, stroma, and immune response. We investigated
      the therapeutic efficacy of anti-TGFbeta receptor II (TGFbeta RII) antibody in
      controlling metastasis and tumor growth as well as enhancing antitumor immunity
      in preclinical tumor models. EXPERIMENTAL DESIGN: We generated neutralizing
      antibodies to TGFbeta RII and assessed the antibody effects on cancer, stroma,
      and immune cells in vitro. The efficacy and mechanism of action of the antibody
      as monotherapy and in combination with chemotherapy in suppression of primary
      tumor growth and metastasis were evaluated in several tumor models. RESULTS: Anti
      TGFbeta RII antibody blocked TGFbeta RII binding to TGFbeta 1, 2, and 3, and
      attenuated the TGFbeta-mediated activation of downstream Smad2 kinase, invasion
      of cancer cells, motility of endothelial and fibroblast cells, and induction of
      immunosuppressive cells. Treatment with the antibody significantly suppressed
      primary tumor growth and metastasis and enhanced natural killer and CTL activity
      in tumor-bearing mice. Immunohistochemistry analysis showed cancer cell apoptosis
      and massive necrosis, and increased tumor-infiltrating T effector cells and
      decreased tumor-infiltrating Gr-1+ myeloid cells in the antibody-treated tumors.
      Fluorescence-activated cell sorting analysis indicated the significant reduction
      of peripheral Gr-1+/CD11b+ myeloid cells in treated animals. Concomitant
      treatment with the cytotoxic agent cyclophosphamide resulted in a significantly
      increased antitumor efficacy against primary tumor growth and metastasis.
      CONCLUSIONS: These preclinical data provide a foundation to support using anti
      TGFbeta RII antibody as a therapeutic agent for TGFbeta RII-dependent cancer with
      metastatic capacity.

PMID- 20145180
TI  - High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed
      Neuroblastoma.
AB  - PURPOSE: Most neuroblastomas initially respond to therapy but many relapse with
      chemoresistant disease. p53 mutations are rare in diagnostic neuroblastomas, but
      we have previously reported inactivation of the p53/MDM2/p14(ARF) pathway in 9 of
      17 (53%) neuroblastoma cell lines established at relapse. HYPOTHESIS:
      Inactivation of the p53/MDM2/p14(ARF) pathway develops during treatment and
      contributes to neuroblastoma relapse. METHODS: Eighty-four neuroblastomas were
      studied from 41 patients with relapsed neuroblastoma including 38 paired
      neuroblastomas at different stages of therapy. p53 mutations were detected by
      automated sequencing, p14(ARF) methylation and deletion by methylation-specific
      PCR and duplex PCR, respectively, and MDM2 amplification by fluorescent in situ
      hybridization. RESULTS: Abnormalities in the p53 pathway were identified in 20 of
      41 (49%) cases. Downstream defects due to inactivating missense p53 mutations
      were identified in 6 of 41 (15%) cases, 5 following chemotherapy and/or at
      relapse and 1 at diagnosis, postchemotherapy, and relapse. The presence of a p53
      mutation was independently prognostic for overall survival (hazard ratio, 3.4;
      95% confidence interval, 1.2-9.9; P = 0.02). Upstream defects were present in 35%
      of cases: MDM2 amplification in 3 cases, all at diagnosis and relapse and
      p14(ARF) inactivation in 12 of 41 (29%) cases: 3 had p14(ARF) methylation, 2
      after chemotherapy, and 9 had homozygous deletions, 8 at diagnosis and relapse.
      CONCLUSIONS: These results show that a high proportion of neuroblastomas which
      relapse have an abnormality in the p53 pathway. The majority have upstream
      defects suggesting that agents which reactivate wild-type p53 would be
      beneficial, in contrast to those with downstream defects in which p53-independent
      therapies are indicated.

PMID- 20145181
TI  - Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas.
AB  - PURPOSE: The objective of this study is to investigate the significance of
      microRNAs (miRNA) in patients with locally advanced head and neck squamous cell
      carcinoma (HNSCC). EXPERIMENTAL DESIGN: A global miRNA profiling was done on 51
      formalin-fixed archival HNSCC samples using quantitative reverse transcription
      PCR approach, correlated with patients' clinical parameters. Functional
      characterization of HNSCC-associated miRNAs was conducted on three HNSCC cell
      lines. Cell viability and proliferation were investigated using MTS and
      clonogenic assays, respectively; cell cycle analyses were assessed using flow
      cytometry. RESULTS: Thirty-eight of the 117 (33%) consistently detected miRNAs
      were significantly differentially expressed between malignant versus normal
      tissues. Concordant with previous reports, overexpression of miR-21, miR-155, let
      7i, and miR-142-3p and underexpression of miR-125b and miR-375 were detected.
      Upregulation of miR-423, miR-106b, miR-20a, and miR-16 as well as downregulation
      of miR-10a were newly observed. Exogenous overexpression of miR-375 in HNSCC cell
      lines reduced proliferation and clonogenicity and increased cells in sub-G(1).
      Similar cellular effects were observed in knockdown studies of the miR-106b-25
      cluster but with accumulation of cells in G(1) arrest. No major difference was
      detected in miRNA profiles among laryngeal, oropharyngeal, or hypopharyngeal
      cancers. miR-451 was found to be the only significantly overexpressed miRNA by
      4.7-fold between nonrelapsed and relapsed patients. CONCLUSION: We have
      identified a group of aberrantly expressed miRNAs in HNSCC and showed that
      underexpression of miR-375 and overexpression of miR-106b-25 cluster might play
      oncogenic roles in this disease. Further detailed examinations of miRNAs will
      provide opportunities to dissect the complex molecular abnormalities driving
      HNSCC progression.

PMID- 20145182
TI  - Finding the right dose for cancer therapeutics--can we do better?
AB  - Unlike other diseases, dose-selection for cancer therapeutics is often based on
      the maximum-tolerated dose in phase 1 studies involving relatively few patients.
      In this issue of Clinical Cancer Research, Jain and colleagues provide evidence
      that lower doses may be as effective as maximum-tolerated doses in the treatment
      of cancer patients.

PMID- 20145184
TI  - Tipifarnib plus tamoxifen in tamoxifen-resistant metastatic breast cancer: a
      negative phase II and screening of potential therapeutic markers by proteomic
      analysis.
AB  - PURPOSE: Tipifarnib, a farnesyltransferase inhibitor, has antitumor activity in
      heavily pretreated metastatic breast cancer patients. Preclinical data suggest
      that FTIs could restore tamoxifen responsiveness in tamoxifen-resistant disease.
      Thus, combining FTIs and tamoxifen may be a promising clinical approach after
      relapse or progression on tamoxifen. EXPERIMENTAL DESIGN: Postmenopausal patients
      with measurable estrogen receptor- and/or progesterone receptor-expressing
      metastatic breast cancers were enrolled. Only patients with disease progression
      on tamoxifen were eligible, but there was no limitation regarding prior
      chemotherapy or hormone therapy regimens. Patients were immediately treated with
      300 mg (n = 12) or 200 mg (n = 10) tipifarnib twice daily for 21 of 28-day cycles
      plus tamoxifen once daily. Serum was collected at baseline and after 8 weeks of
      treatment to enable proteomic comparison and identify possible predictive
      response markers. RESULTS: Twenty patients were enrolled and evaluated for
      efficacy: one patient had an objective response (liver metastasis) and nine had
      stable disease after 6 months for a clinical benefit rate of 50%; median duration
      of benefit was 10.3 (range, 7.4-20.2) months. The proteomic analysis by SELDI-TOF
      and LTQ-FT-Orbitrap identified a known peptide of fibrinogen alpha, the intensity
      of which was significantly increased in patients with progression compared with
      patients who benefited from the combined treatment after 8 weeks. CONCLUSIONS:
      Because the primary end point of efficacy (three objective responses) was not
      achieved, the study is negative. Nevertheless, the identified peptide could be of
      interest in discriminating, at 8 weeks of treatment, responders from
      nonresponders.

PMID- 20145183
TI  - Phase I trial of pelvic radiation, weekly cisplatin, and 3-aminopyridine-2
      carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) for locally advanced
      cervical cancer.
AB  - PURPOSE: This study assessed the safety/tolerability, pharmacokinetics, and
      clinical activity of three times weekly i.v. 3-aminopyridine-2-carboxaldehyde
      thiosemicarbazone (3-AP, NSC #663249) in combination with once-weekly i.v.
      cisplatin and daily pelvic radiation in patients with gynecologic malignancies. 3
      AP is a novel small-molecule inhibitor of ribonucleotide reductase (RNR) and is
      being tested as a potential radiosensitizer and chemosensitizer. EXPERIMENTAL
      DESIGN: Patients with stage IB2 to IVB cervical cancer (n = 10) or recurrent
      uterine sarcoma (n = 1) were assigned to dose-finding cohorts of 2-hour 3-AP
      infusions during 5 weeks of cisplatin chemoradiation. Pharmacokinetic and
      methemoglobin samples and tumor biopsy for RNR activity were obtained on day 1
      and day 10. Clinical response was assessed. RESULTS: The maximum tolerated 3-AP
      dose was 25 mg/m(2) given three times weekly during cisplatin and pelvic
      radiation. Two patients experienced manageable 3-AP-related grade 3 or 4
      electrolyte abnormalities. 3-AP pharmacokinetics showed a 2-hour half-life, with
      median peak plasma concentrations of 277 ng/mL (25 mg/m(2)) and 467 ng/mL (50
      mg/m(2)). Median methemoglobin levels peaked at 1% (25 mg/m(2)) and 6% (50
      mg/m(2)) at 4 hours after initiating 3-AP infusions. No change in RNR activity
      was found on day 1 versus day 10 in six early complete responders, whereas
      elevated RNR activity was seen on day 10 as compared with day 1 in four late
      complete responders (P = 0.02). Ten (100%) patients with stage IB2 to IVB
      cervical cancer achieved complete clinical response and remained without disease
      relapse with a median 18 months of follow-up (6-32 months). CONCLUSIONS: 3-AP was
      well tolerated at a three times weekly i.v. 25 mg/m(2) dose during cisplatin and
      pelvic radiation. Clin Cancer Res; 16(4); 1298-306.

PMID- 20145185
TI  - AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth
      factor receptor, ERBB2 (HER2), and ERBB3: a unique agent for simultaneous ERBB
      receptor blockade in cancer.
AB  - PURPOSE: To test the hypothesis that simultaneous, equipotent inhibition of
      epidermal growth factor receptor (EGFR; erbB1), erbB2 (human epidermal growth
      factor receptor 2), and erbB3 receptor signaling, using the novel small-molecule
      inhibitor AZD8931, will deliver broad antitumor activity in vitro and in vivo.
      EXPERIMENTAL DESIGN: A range of assays was used to model erbB family receptor
      signaling in homodimers and heterodimers, including in vitro evaluation of erbB
      kinase activity, erbB receptor phosphorylation, proliferation in cells, and in
      vivo testing in a human tumor xenograft panel, with ex vivo evaluation of erbB
      phosphorylation and downstream biomarkers. Gefitinib and lapatinib were used to
      compare the pharmacological profile of AZD8931 with other erbB family inhibitors.
      RESULTS: In vitro, AZD8931 showed equipotent, reversible inhibition of EGFR
      (IC(50), 4 nmol/L), erbB2 (IC(50), 3 nmol/L), and erbB3 (IC(50), 4 nmol/L)
      phosphorylation in cells. In proliferation assays, AZD8931 was significantly more
      potent than gefitinib or lapatinib in specific squamous cell carcinoma of the
      head and neck and non-small cell lung carcinoma cell lines. In vivo, AZD8931
      inhibited xenograft growth in a range of models while significantly affecting
      EGFR, erbB2, and erbB3 phosphorylation and downstream signaling pathways,
      apoptosis, and proliferation. CONCLUSIONS: AZD8931 has a unique pharmacologic
      profile providing equipotent inhibition of EGFR, erbB2, and erbB3 signaling and
      showing greater antitumor activity than agents with a narrower spectrum of erbB
      receptor inhibition in specific preclinical models. AZD8931 provides the
      opportunity to investigate whether simultaneous inhibition of erbB receptor
      signaling could be of utility in the clinic, particularly in the majority of
      solid tumors that do not overexpress erbB2.

PMID- 20145186
TI  - A phase I safety and pharmacokinetic study of the death receptor 5 agonistic
      antibody PRO95780 in patients with advanced malignancies.
AB  - PURPOSE: PRO95780 is a fully human IgG1 monoclonal antibody that triggers the
      extrinsic apoptosis pathway through death receptor 5. This first-in-human study
      assessed the safety, tolerability, pharmacokinetics, and any early evidence of
      efficacy of PRO95780 in patients with advanced malignancies. EXPERIMENTAL DESIGN:
      Target concentrations were predicted to occur at 10 mg/kg. Patients received up
      to eight cycles of PRO95780 i.v. using a 3+3 dose escalation design at 1 to 20
      mg/kg every 14 days (every 28 days in cycle 1; stage 1), with cohort expansion at
      either the maximum tolerated dose or 10 mg/kg, whichever was lower (stage 2).
      Patients were evaluated for response every other cycle. RESULTS: The maximum
      tolerated dose was not reached within this study. Four (8%) of 50 patients
      reported adverse events of greater than grade 2 at least possibly related to
      PRO95780, including 2 patients with reversible grade 3 transaminase elevation.
      The mean terminal half-life was 8.8 to 19.3 days, with dose-dependent increases
      in exposure (peak plasma concentration and area under the concentration) across 1
      to 15 mg/kg. Most patients treated with 10 mg/kg or above achieved trough
      concentration above the target efficacious concentration at day 15 with moderate
      accumulation after multiple doses. No objective responses occurred, although
      three minor responses were observed in patients with colorectal and granulosa
      cell ovarian cancers (each treated with 4 mg/kg) and chondrosarcoma (10 mg/kg).
      CONCLUSIONS: PRO95780 is safe and well tolerated at doses up to 20 mg/kg.
      Evidence of activity was noted in several different tumor types at 4 and 10
      mg/kg. Pharmacokinetic analysis supports a dosing regimen of 10 to 15 mg/kg every
      2 to 3 weeks.

PMID- 20145187
TI  - Phase I oncology studies: evidence that in the era of targeted therapies patients
      on lower doses do not fare worse.
AB  - PURPOSE: To safely assess new drugs, cancer patients in initial cohorts of phase
      I oncology studies receive low drug doses. Doses are successively increased until
      the maximum tolerated dose (MTD) is determined. Because traditional chemotherapy
      is often more effective near the MTD, ethical concerns have been raised about
      administration of low drug doses to phase I patients. However, a substantial
      portion of oncology trials now investigate targeted agents, which may have
      different dose-response relationships than cytotoxic chemotherapies. EXPERIMENTAL
      DESIGN: Twenty-four consecutive trials treating 683 patients between October 1,
      2004, and June 30, 2008, at MD Anderson Cancer Center were analyzed. Patients
      were assigned to a low-dose (<or=25% MTD), medium-dose (25-75% MTD), or high-dose
      (>or=75% MTD) group, and groups were compared for response rate, time-to
      treatment failure, progression-free survival, overall survival, and toxicity. To
      remove negatively biasing data from the high-dose group, in a second analysis,
      patients treated above the MTD were excluded (high-dose group, 75-100% MTD). Of
      the 683 patients, 97.7% received targeted agents. RESULTS: Even when excluding
      patients above the MTD, there was an early trend favoring the low- versus high
      dose group in time-to-treatment failure, with 32.9% versus 25.2% of patients on
      therapy at 3 months (P = 0.08). In addition, the low-dose group fared at least as
      well as the other groups in all other outcomes, including response rate,
      progression-free survival, overall survival, and toxicity. CONCLUSIONS: These
      data may help alleviate concerns that patients who receive low drug doses on
      contemporary phase I oncology trials fare worse and suggest targeted agents may
      have different dose-response relationships than cytotoxic chemotherapies.

PMID- 20145188
TI  - Elevated phosphate activates N-ras and promotes cell transformation and skin
      tumorigenesis.
AB  - Recent results suggest a paradigm shift from viewing inorganic phosphate as a
      passive requirement for basic cell functions to an active regulator of cell
      behavior. We have previously shown that elevated concentrations of phosphate
      increased cell proliferation and expression of protumorigenic genes such as Fra-1
      and osteopontin in a preosteoblast cell line. Therefore, we hypothesized that
      elevated phosphate concentrations would promote cell transformation in vitro and
      tumorigenesis in vivo. Supplementation of medium with phosphate increased
      anchorage-independent transformation and proliferation of BALB/c mouse JB6
      epidermal cells, activation of N-ras, ERK1/2, and activator protein-1, and
      increased gene expression of Fra-1, COX-2, and osteopontin in a dose-dependent
      manner. These in vitro results led to the hypothesis that varying the levels of
      dietary inorganic phosphate would alter tumorigenesis in the mouse model of skin
      carcinogenesis. Female FVB/N mice were treated with 7,12
      dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate and fed high- or
      low-phosphate diets (1.2% versus 0.2% of the diet) for 19 weeks. The high
      phosphate diet increased skin papilloma number by approximately 50% without
      changing feed intake and body weights. High dietary phosphate increased serum
      concentrations of phosphate, parathyroid hormone, and osteopontin and decreased
      serum concentrations of calcium. Thus, we conclude that elevated phosphate
      promotes cell transformation and skin tumorigenesis partly by increasing the
      availability of phosphate for activation of N-ras and its downstream targets,
      which defines reducing dietary phosphate as a novel target for chemoprevention.

PMID- 20145189
TI  - Differential inhibition of protein translation machinery by curcumin in normal,
      immortalized, and malignant oral epithelial cells.
AB  - Curcumin has shown some promise in the prevention of oral carcinogenesis by
      mechanism(s) that are still not completely resolved. Messenger RNA translation is
      mediated in eukaryotes by the eIF4F complex composed of eukaryotic translation
      initiation factors eIF4E, eIF4G, and eIF4A. Overexpression of some of these
      components or the inactivation of initiation repressor proteins (4E-BP1) has been
      implicated in cancer development including oral carcinogenesis by affecting cell
      survival, angiogenesis, and tumor growth and invasion. In this study, we examined
      the possibility that curcumin affects the translational machinery differently in
      normal, immortalized normal, leukoplakia, and malignant cells. Curcumin treatment
      in vitro inhibited the growth of immortalized oral mucosa epithelial cells (NOM9
      CT) and the leukoplakia cells (MSK-Leuk1s) as well as in the UMSCC22B and SCC4
      cells derived from head and neck squamous cell carcinoma. Curcumin only exerted
      minor effects on the growth of normal oral epithelial cells (NOM9). In the
      immortalized, leukoplakia, and cancer cells, curcumin inhibited cap-dependent
      translation by suppressing the phosphorylation of 4E-BP1, eIF4G, eIF4B, and Mnk1,
      and also reduced the total levels of eIF4E and Mnk1. Our findings show that
      immortalized normal, leukoplakia, and malignant oral cells are more sensitive to
      curcumin and show greater modulation of protein translation machinery than the
      normal oral cells, indicating that targeting this process may be an important
      approach to chemoprevention in general and for curcumin in particular.

PMID- 20145190
TI  - Null activity of selenium and vitamin e as cancer chemopreventive agents in the
      rat prostate.
AB  - To evaluate the potential efficacy of selenium and vitamin E as inhibitors of
      prostate carcinogenesis, four chemoprevention studies using a common protocol
      were done in a rat model of androgen-dependent prostate cancer. After stimulation
      of prostate epithelial cell proliferation by a sequential regimen of cyproterone
      acetate followed by testosterone propionate, male Wistar-Unilever rats received a
      single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic
      androgen stimulation via subcutaneous implantation of testosterone pellets. At 1
      week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a
      basal diet or a basal diet supplemented with l-selenomethionine (3 or 1.5 mg/kg
      diet; study 1), dl-alpha-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study
      2), l-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet;
      study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study
      4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate
      cancer incidence was determined by histopathologic evaluation. No statistically
      significant reductions in prostate cancer incidence were identified in any group
      receiving dietary supplementation with selenium and/or vitamin E. These data do
      not support the hypotheses that selenium and vitamin E are potent cancer
      chemopreventive agents in the prostate, and when considered with the recent
      clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial
      (SELECT), show the predictive nature of this animal model for human prostate
      cancer chemoprevention.

PMID- 20145191
TI  - Parity-induced decrease in systemic growth hormone alters mammary gland
      signaling: a potential role in pregnancy protection from breast cancer.
AB  - Early full-term pregnancy is an effective natural protection against breast
      cancer in both humans and experimental rodents. The protective effect of an early
      pregnancy is, in part, linked to changes in circulating hormones that are
      involved in both normal breast development and breast cancer. For example, a
      reduction in circulating growth hormone (GH) has been shown to protect rats from
      carcinogen-induced mammary tumors. We examined the ability of a full-term
      pregnancy to alter the endocrine GH/insulin-like growth factor-I (IGF-I) axis and
      how this change affected normal mammary gland function in two commonly used rat
      models (Sprague-Dawley and Wistar Furth). Circulating GH and IGF-I were measured
      in blood drawn every 30 minutes from parous and age-matched virgin female rats.
      Mean serum GH levels were significantly decreased (P < 0.01) in parous compared
      with age-matched virgin rats for both strains. Changes in GH levels were
      independent of estrous cycle, indicated by a significant (P < 0.05) reduction in
      circulating levels of GH during estrus and diestrus in both parous strains.
      Despite the decrease in circulating GH, pituitary GH mRNA levels were unaltered
      in parous rats. Circulating IGF-I and hepatic IGF-I mRNA were also unaltered by
      parity in either rat strain. Immunoblot analysis of mammary glands showed
      decreases in phosphorylation of signal transducer and activator of transcription
      5A and Janus-activated kinase 2, suggesting reduced action of GH in the mammary
      gland. Therefore, although the parity reduction in circulating GH does not affect
      circulating IGF-I levels, it is possible that reduced GH acts directly at the
      mammary gland and may play a role in pregnancy protection from breast cancer.

PMID- 20145192
TI  - Limited-stage small cell lung cancer: current chemoradiotherapy treatment
      paradigms.
AB  - In the U.S., the prevalence of small cell lung cancer (SCLC) is declining,
      probably reflecting the decreasing prevalence of tobacco use. However, a
      significant number of patients will receive a diagnosis of SCLC, and
      approximately 40% of patients with SCLC will have limited-stage (LS) disease,
      which is potentially curable with the combination of chemotherapy and radiation
      therapy. The standard therapy for LS-SCLC is concurrent chemoradiotherapy, and
      the 5-year survival rate observed in clinical trials is approximately 25%. The
      standard chemotherapy remains cisplatin and etoposide, but carboplatin is
      frequently used in patients who cannot tolerate or have a contraindication to
      cisplatin. Substantial improvements in survival have been made through
      improvements in radiation therapy. Concurrent chemoradiotherapy is the preferred
      therapy for patients who are appropriate candidates. The optimal timing of
      concurrent chemoradiotherapy is during the first or second cycle, based on data
      from meta-analyses. The optimal radiation schedule and dose remain topics of
      debate, but 1.5 Gy twice daily to a total of 45 Gy and 1.8-2.0 Gy daily to a
      total dose of 60-70 Gy are commonly used treatments. For patients who obtain a
      near complete or complete response, prophylactic cranial radiation reduces the
      incidence of brain metastases and improves overall survival. The ongoing
      Radiation Therapy Oncology Group and Cancer and Leukemia Group B and the European
      and Canadian phase III trials will investigate different radiation treatment
      paradigms for patients with LS-SCLC, and completion of these trials is critical.

PMID- 20145193
TI  - What is a world-class medical facility?

PMID- 20145194
TI  - Cataract surgery among veterans 65 years of age and older: analysis of national
      veterans health administration databases.
AB  - The authors examine the rates of cataract surgery as a crude measure of
      appropriateness of care among veterans 65 years of age and older who use Veterans
      Health Administration (VHA). Data were obtained from the national VHA data sets
      for fiscal years 2000 through 2007, using International Classification of
      Diseases codes and the American Medical Association's Current Procedural
      Terminology codes. Cataract surgery was expressed as procedures per 10 000
      veteran beneficiaries per fiscal year. The annual incidence of cataract surgery
      increased marginally over the study period with an average annual incidence of
      105.8 surgeries per 10 000 beneficiaries. Institutional rates of VHA surgery
      differ substantially from those of Medicare beneficiaries, which are
      approximately 5.5-fold greater. Although direct comparison must be interpreted
      cautiously, the difference is too great to be explained by demographic factors or
      secular trends in surgery. Additional research is required to elucidate factors
      that influence the rate of cataract surgery in the VHA.

PMID- 20145195
TI  - In-hospital death of critically ill patients who have congestive heart failure:
      does size of hospital matter?
AB  - Data from the British Columbia Linked Health Database were analyzed to determine
      if size of hospital is associated with in-hospital death of critically ill adults
      whose admitting diagnosis is congestive heart failure (CHF). Patients who were
      <19 years of age, transferred from or to other hospitals, or who developed CHF as
      a complication were excluded. In unadjusted logistic regression analysis of 2616
      patients, the odds ratio (OR) for in-hospital death associated with a doubling of
      the number of hospital beds was 1.12 (95% confidence interval [CI] = 1.03-1.23; P
      = .01). After adjustment for age, sex, CHF-specific comorbidity index, number of
      cardiac and noncardiac procedures, number of hospital admissions for CHF in the
      preceding year, and socioeconomic variables, the OR was 1.08 (95% CI = 0.96-1.20;
      P = .21). The conclusion is that the adjusted rate of in-hospital deaths for this
      patient group does not differ significantly based solely on the number of acute
      hospital beds.

PMID- 20145196
TI  - Intimate partner violence during pregnancy: a pilot intervention program in Lima,
      Peru.
AB  - This pilot study examined the effectiveness of standard care and an empowerment
      intervention for abused pregnant women. Severe psychological abuse was most
      prevalent (42.2%) among this sample of women. Compared with women in the standard
      care group at the postintervention survey, women in the empowerment group were
      more likely to hide money (44.6% vs. 34.3%), establish a code with family or
      friends (19.6% vs. 16.2%), ask neighbors to call police if violence began (6.9%
      vs. 1.0%), had available bank account numbers (17.1% vs. 3.1%), had valuable
      jewelry (8.4% vs. 3.8%), and had available a hidden bag with extra clothing (9.0%
      vs. 3.1%). However, there was no statistically significant difference in health
      related quality of life, adoption of safety behaviors, and use of community
      resources between women in the two groups. Simply asking pregnant women about
      abuse and offering referral could potentially interrupt and prevent further
      abuse.

PMID- 20145198
TI  - HIV-1 Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral
      production from latency.
AB  - Vpr, a HIV-1 accessory protein, was believed to be present in the plasma of HIV-1
      positive patients, and our previous work demonstrated the presence of plasma Vpr
      in 20 out of 52 patients. Interestingly, our data revealed that patients' viral
      titer was correlated with the level of Vpr detected in their plasma. Here, we
      first show that rVpr, when incubated with human monocytes or MDMs, caused viral
      production from latently infected cells, and IL-6 was identified as a responsible
      factor. The induction of IL-6 by rVpr was dependent on signaling through TLR4 and
      its adaptor molecule, MyD88. We next provide evidence that rVpr induced the
      formation of OxPC and that a mAb against OxPC blocked rVpr-induced IL-6
      production with the concomitant attenuation of MAPK activation. Moreover, the
      addition of NAC, a scavenger of ROS, abrogated the rVpr-induced formation of
      OxPC, the phosphorylation of C/EBP-beta, a substrate of MAPK, and IL-6
      production. As rIL-6 reactivated viral replication in latently infected cells,
      our data indicate that rVpr-induced oxidative stress triggers cell-based innate
      immune responses and reactivates viral production in latently infected cells via
      IL-6 production. Our results suggest that Vpr should be monitored based on the
      viral titer, and they provide the rationale for the development of novel, anti
      AIDS therapeutics targeting Vpr.

PMID- 20145199
TI  - Heterogeneity in a mouse model of histiocytosis: transformation of Langerin+
      dendritic cells, macrophages, and precursors.
AB  - Neoplastic diseases of macrophages (M phi) and dendritic cells (DC), collectively
      called histiocytoses, are relatively rare. The etiology of most forms of
      histiocytosis is poorly understood, and the development of animal models is
      crucial for further research in this field. Previously, an animal model for
      malignant histiocytosis (MH), involving transformed histiocytic cells, has been
      generated by infecting mice with malignant histiocytosis sarcoma virus (MHSV).
      However, increased insight into the heterogeneity of M phi and DC, and the
      associated reappraisal of human proliferative diseases involving these cells
      inspired us to re-evaluate the mouse model. We analyzed spleen, bone marrow, and
      lymph nodes of susceptible mice at various time points after infection. From day
      11 onwards, a heterogeneous population of cells, consisting of CD8 alpha(+)
      Langerin(+) DC, ER-MP58(+) CD11b(+) myeloid precursor cells, CD169(+)
      metallophilic M phi, and CD71(hi) erythroblasts, was affected by viral
      transformation. In different mice, these subsets expanded at different rates in
      different organs, causing a variable disease profile in terminal stages. Cell
      lines, which were generated from MHSV-transformed tumors, showed a DC-like
      morphology and phenotype, and appeared to be arrested in different stages of
      maturation. Upon injection into healthy mice, different preferential homing
      patterns were observed for the various cell lines, and the cells acquired
      distinct phenotypes depending on the organ of homing. This indicates that these
      transformed cells adapt to their microenvironment by switching between precursor,
      DC/Langerhans cell, and M phi phenotypes. Our results demonstrate that the MHSV
      model represents a heterogeneous neoplastic disease with characteristics of M
      phi/DC sarcomas.

PMID- 20145197
TI  - Plasmacytoid dendritic cells in HIV infection: striking a delicate balance.
AB  - pDC are the most potent IFN-alpha-producing cells in the body and serve as a
      vital link between innate and adaptive immunity. Deficiencies in pDC function
      were among the earliest observations of immune dysfunction in HIV-1 infection.
      Herein, we review the status of pDC in individuals with HIV-1 infection and the
      potential role of these cells in pathogenesis. We begin by reviewing the basic
      properties of pDC and then discuss the compromise in circulating pDC numbers and
      function in early and viremic HIV-1 infection and mechanisms that might account
      for their depletion in HIV-infected patients. In addition, we review the evidence
      that chronic production of IFN-alpha, probably through the chronic activation of
      pDC, is central to the immune activation that is so detrimental in HIV infection.
      Finally, we discuss the importance of balance in pDC numbers and function and the
      potential value of using absolute pDC counts and function as a biomarker, along
      with CD4(+) cell counts and VL in HIV-1-infected patients.

PMID- 20145200
TI  - Protein tyrosine phosphatase SHP-1 positively regulates TLR-induced IL-12p40
      production in macrophages through inhibition of phosphatidylinositol 3-kinase.
AB  - SHP-1 is a cytoplasm protein tyrosine phosphatase expressed primarily in
      hematopoietic cells. In the immune system, SHP-1 plays critical roles in
      regulation of many receptor-mediated signaling cascades, and SHP-1 deficiency in
      mice causes spontaneous inflammation and autoimmunity. Here, we report a unique
      requirement for SHP-1 in interleukin-12/23 p40 (IL-12p40) production in response
      to Toll-like receptor (TLR) stimulation in macrophages. Bone marrow-derived
      macrophages (BMDMs) lacking significant SHP-1 activity display a profound defect
      in IL-12p40 synthesis in response to lipopolysaccharide, peptidoglycan, and
      synthetic TLR ligands, while producing normal amounts of other proinflammatory
      cytokines, such as TNFalpha and IL-6. Inhibition of SHP-1 function in wild-type
      BMDMs decreases IL-12p40, and expression of functional SHP-1 protein in mutant
      cells restores IL-12p40 production following TLR ligation. SHP-1 regulation of IL
      12p40 transcription requires both its catalytic activity and phosphotyrosine
      binding by its N-terminal SH2 domain and is mediated via repression of, and
      interaction with, phosphatidylinositol 3-kinase, without affecting c-Rel
      activation. In contrast to normal NF-kappaB activation, SHP-1-defective
      me(v)/me(v) macrophages display a defect in nucleosome remodeling at the IL-12p40
      promoter, and phosphatidylinositol 3-kinase inhibition significantly restores
      normal nucleosome remodeling in me(v)/me(v) macrophages. Thus, there is a
      critical role for the tyrosine phosphatase activity of SHP-1 for induction of IL
      12p40 production in macrophages in response to TLR ligands, a novel mechanism for
      host regulation of a specific proinflammatory cytokine important in both innate
      and adaptive immunity.

PMID- 20145201
TI  - Myoglobin-deficient mice activate a distinct cardiac gene expression program in
      response to isoproterenol-induced hypertrophy.
AB  - Myoglobin knockout mice (myo-/-) adapt to the loss of myoglobin by the activation
      of a variety of compensatory mechanisms acting on the structural and functional
      level. To analyze to what extent myo-/- mice would tolerate cardiac stress we
      used the model of chronic isoproterenol application to induce cardiac hypertrophy
      in myo-/- mice and wild-type (WT) controls. After 14 days of isoproterenol
      infusion cardiac hypertrophy in WT and myo-/- mice reached a similar level. WT
      mice developed lung edema and left ventricular dilatation suggesting the
      development of heart failure. In contrast, myo-/- mice displayed conserved
      cardiac function and no signs of left ventricular dilatation. Analysis of the
      cardiac gene expression profiles using 40K mouse oligonucleotide arrays showed
      that isoproterenol affected the expression of 180 genes in WT but only 92 genes
      of myo-/- hearts. Only 40 of these genes were regulated in WT as well as in myo-/
      hearts. In WT hearts a pronounced induction of genes of the extracellular matrix
      occurred suggesting a higher level of cardiac remodeling. myo-/- hearts showed
      altered transcription of genes involved in carbon metabolism, inhibition of
      apoptosis and muscular repair. Interestingly, a subset of genes that was altered
      in myo-/- mice already under basal conditions was differentially expressed in WT
      hearts under isoproterenol treatment. In summary, our data show a high capacity
      of myoglobin-deficient mice to adapt to catecholamine induced cardiac stress
      which is associated with activation of a distinct cardiac gene expression
      program.

PMID- 20145203
TI  - Distinctive patterns of age-dependent hypomethylation in interspersed repetitive
      sequences.
AB  - Interspersed repetitive sequences (IRSs) are a major contributor to genome size
      and may contribute to cellular functions. IRSs are subdivided according to size
      and functionally related structures into short interspersed elements, long
      interspersed elements (LINEs), DNA transposons, and LTR-retrotransposons. Many
      IRSs may produce RNA and regulate genes by a variety of mechanisms. The majority
      of DNA methylation occurs in IRSs and is believed to suppress IRS activities.
      Global hypomethylation, or the loss of genome-wide methylation, is a common
      epigenetic event not only in senescent cells but also in cancer cells. Loss of
      LINE-1 methylation has been characterized in many cancers. Here, we evaluated the
      methylation levels of peripheral blood mononuclear cells of LINE-1, Alu, and
      human endogenous retrovirus K (HERV-K) in 177 samples obtained from volunteers
      between 20 and 88 yr of age. Age was negatively associated with methylation
      levels of Alu (r = -0.452, P < 10(-3)) and HERV-K (r = -0.326, P < 10(-3)) but
      not LINE-1 (r = 0.145, P = 0.055). Loss of methylation of Alu occurred during
      ages 34-68 yr, and loss of methylation of HERV-K occurred during ages 40-63 yr
      and again during ages 64-83 yr. Interestingly, methylation of Alu and LINE-1 are
      directly associated, particularly at ages 49 yr and older (r = 0.49, P < 10(-3)).
      Therefore, only some types of IRSs lose methylation at certain ages. Moreover,
      Alu and HERV-K become hypomethylated differently. Finally, there may be several
      mechanisms of global methylation. However, not all of these mechanisms are age
      dependent. This finding may lead to a better understanding of not only the
      biological causes and consequences of genome-wide hypomethylation but also the
      role of IRSs in the aging process.

PMID- 20145202
TI  - Distinctive patterns of microRNA expression in extraocular muscles.
AB  - The extraocular muscles (EOMs) are a unique group of muscles that are
      anatomically and physiologically distinct from other muscles. We and others have
      shown that EOMs have a unique transcriptome and proteome. Here we investigated
      the expression pattern of microRNAs (miRNAs), as they may play a role in
      generating the unique EOM allotype. We isolated RNA and screened LC Sciences
      miRNA microarrays covering the sequences of miRBase 10.0 to define the
      microRNAome of normal mouse EOM and tibialis anterior (TA) limb muscle. Seventy
      four miRNAs were found to be differentially regulated (P value <0.05) of which 31
      (14 upregulated, 17 downregulated) were differentially regulated at signal
      strength >500. Muscle-specific miRNAs miR-206 and miR-499 were upregulated and
      miR-1, miR-133a, and miR-133b were downregulated in EOM. Quantitative PCR (qPCR)
      analysis was used to validate the differential expression. Bioinformatic tools
      were used to identify potential miRNA-mRNA-protein interactions and integrate
      data with previous transcriptome and proteomic profiling data. Luciferase assays
      using cotransfection of precursor miRNAs with reporter constructs containing the
      3'-untranslated region of predicted target genes were used to validate targeting
      by identified miRNAs. The definition of the EOM microRNAome complements existing
      transcriptome and proteome data about the molecular makeup of EOM and provides
      further insight into regulation of muscle genes. These data will also help to
      further explain the unique EOM muscle allotype and its differential sensitivity
      to diseases such as Duchenne muscular dystrophy and may assist in development of
      therapeutic strategies. 

PMID- 20145204
TI  - T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral
      ethanol preference.
AB  - Elevated alcohol consumption is associated with enhanced preference for sweet
      substances across species and may be mediated by oral alcohol-induced activation
      of neurobiological substrates for sweet taste. Here, we directly examined the
      contribution of the T1r3 receptor protein, important for sweet taste detection in
      mammals, to ethanol intake and preference and the neural processing of ethanol
      taste by measuring behavioral and central neurophysiological responses to oral
      alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain.
      T1r3 knockout and wild-type mice were tested in behavioral preference assays for
      long-term voluntary intake of a broad concentration range of ethanol, sucrose,
      and quinine. For neurophysiological experiments, separate groups of mice of each
      genotype were anesthetized, and taste responses to ethanol and stimuli of
      different taste qualities were electrophysiologically recorded from gustatory
      neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were
      behaviorally indifferent to alcohol (i.e., ~50% preference values) at
      concentrations typically preferred by wild-type mice (5-15%). Central neural
      taste responses to ethanol in T1r3-deficient mice were significantly lower
      compared with C57BL/6J controls, a strain for which oral ethanol stimulation
      produced a concentration-dependent activation of sweet-responsive NTS gustatory
      neurons. An attenuated difference in ethanol preference between knockouts and
      controls at concentrations >15% indicated that other sensory and/or postingestive
      effects of ethanol compete with sweet taste input at high concentrations. As
      expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural
      taste responses to sweeteners but did not differ from wild-type mice in responses
      to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3
      receptor in the sensory detection and transduction of ethanol taste. 

PMID- 20145206
TI  - Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic,
      and xenogeneic natural killer cells.
AB  - Multipotent adult germ-line stem cells (maGSCs) and induced pluripotent stem
      cells (iPSCs) could be used to generate autologous cells for therapeutic
      purposes, which are expected to be tolerated by the recipient. However, effects
      of the immune system on these cells have not been investigated. We have compared
      the susceptibility of maGSC lines to IL-2-activated natural killer (NK) cells
      with embryonic stem cell (ESC) lines, iPSCs, and F9 teratocarcinoma cells. The
      killing of pluripotent cell lines by syngeneic, allogeneic, and xenogeneic killer
      cells ranged between 48 and 265% in chromium release assays when compared to YAC
      1 cells, which served as highly susceptible reference cells. With the exception
      of 2 maGSC lines, they expressed ligands for the activating NK receptor NKG2D
      that belong to the RAE-1 family, and killing could be inhibited by soluble NKG2D,
      demonstrating a functional role of these molecules. Furthermore, ligands of the
      activating receptor DNAM-1 were frequently expressed. The susceptibility to NK
      cells might constitute a common feature of pluripotent cells. It could result in
      rejection after transplantation, as suggested by a reduced teratoma growth after
      NK cell activation in vivo, but it might also offer a strategy to deplete
      contaminating pluripotent cells before grafting of differentiated cells.

PMID- 20145205
TI  - The midregion, nuclear localization sequence, and C terminus of PTHrP regulate
      skeletal development, hematopoiesis, and survival in mice.
AB  - The functions of parathyroid hormone-related protein (PTHrP) on morphogenesis,
      cell proliferation, apoptosis, and calcium homeostasis have been attributed to
      its N terminus. Evidence suggests that many of these effects are not mediated by
      the N terminus but by the midregion, a nuclear localization sequence (NLS), and C
      terminus of the protein. A knock-in mouse lacking the midregion, NLS, and C
      terminus of PTHrP (Pthrp(Delta/Delta)) was developed. Pthrp(Delta/Delta) mice had
      craniofacial dysplasia, chondrodysplasia, and kyphosis, with most mice dying by d
      5 of age. In bone, there were fewer chondrocytes and osteoblasts per area, bone
      mass was decreased, and the marrow was less cellular, with erythroid hypoplasia.
      Cellular proliferation was impaired, and apoptosis was increased. Runx2, Ocn,
      Sox9, Crtl1, beta-catenin, Runx1, ephrin B2, cyclin D1, and Gata1 were
      underexpressed while P16/Ink4a, P21, GSK-3beta, Il-6, Ffg3, and Ihh were
      overexpressed. Mammary gland development was aberrant, and energy metabolism was
      deregulated. These results establish that the midregion, NLS, and C terminus of
      PTHrP are crucial for the commitment of osteogenic and hematopoietic precursors
      to their lineages, and for survival, and many of the effects of PTHrP on
      development are not mediated by its N terminus. The down-regulation of Runx1,
      Runx2, and Sox9 indicates that PTHrP is a modulator of transcriptional activation
      during stem cell commitment.

PMID- 20145207
TI  - Glucocorticoid receptor DNA binding decoy is a gas.
AB  - The glucocorticoid receptor (GR) is a paradigmatic DNA binding transcription
      factor and was described over 20 years ago as one of the first proteins
      identified to bind the enhancer region of genes called "response elements." Since
      that time, an immense amount of work has revealed that GR transcriptional
      regulation is controlled at virtually every step of its activity: ligand binding,
      nuclear translocation, transcriptional cofactor binding, and DNA binding. Just
      when the major modes of GR regulation appear known, a new study provides yet
      another mechanism whereby GR transcriptional activity is controlled under
      conditions of cell growth arrest. In this case, GR activity is repressed by a
      small noncoding RNA (ncRNA) from the growth arrest-specific transcript 5 gene
      that folds into a soluble glucocorticoid response element-like sequence and
      serves as a decoy for GR DNA binding. This unexpected mode of regulation by
      nucleic acid molecular mimicry is probably not confined to GR and should spark
      interest in the hunt for other ncRNAs that regulate transcription factor binding
      to DNA.

PMID- 20145208
TI  - SUMOylation mediates the nuclear translocation and signaling of the IGF-1
      receptor.
AB  - The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in
      developmental and cancer biology. Most of its biological effects have been
      ascribed to its tyrosine kinase activity, which propagates signaling through the
      phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways.
      Here, we report that IGF-1 promotes the modification of IGF-1R by small ubiquitin
      like modifier protein-1 (SUMO-1) and its translocation to the nucleus. Nuclear
      IGF-1R associated with enhancer-like elements and increased transcription in
      reporter assays. The SUMOylation sites of IGF-1R were identified as three
      evolutionarily conserved lysine residues-Lys(1025), Lys(1100), and Lys(1120)-in
      the beta subunit of the receptor. Mutation of these SUMO-1 sites abolished the
      ability of IGF-1R to translocate to the nucleus and activate transcription but
      did not alter its kinase-dependent signaling. Thus, we demonstrate a SUMOylation
      mediated mechanism of IGF-1R signaling that has potential implications for gene
      regulation.

PMID- 20145210
TI  - Big databases: outcomes research begins to yield results.

PMID- 20145209
TI  - ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling
      pathway.
AB  - Mammalian target of rapamycin (mTOR) regulates various cellular functions,
      including tumorigenesis, and is inhibited by the tuberous sclerosis 1 (TSC1)-TSC2
      complex. Here, we demonstrate that arrest-defective protein 1 (ARD1) physically
      interacts with, acetylates, and stabilizes TSC2, thereby repressing mTOR
      activity. The inhibition of mTOR by ARD1 inhibits cell proliferation and
      increases autophagy, thereby inhibiting tumorigenicity. Correlation between ARD1
      and TSC2 abundance was apparent in multiple tumor types. Moreover, evaluation of
      loss of heterozygosity at Xq28 revealed allelic loss in 31% of tested breast
      cancer cell lines and tumor samples. Together, our findings suggest that ARD1
      functions as an inhibitor of the mTOR pathway and that dysregulation of the ARD1
      TSC2-mTOR axis may contribute to cancer development.

PMID- 20145211
TI  - StatBite: FDA oncology drug product approvals in 2009.

PMID- 20145212
TI  - In silico research: pushing it into the mainstream.

PMID- 20145213
TI  - BRAF inhibitors: research accelerates in wake of positive findings.

PMID- 20145214
TI  - Indolent lymphoma: can rituximab resolve the watch-and-wait debate?

PMID- 20145215
TI  - The cover. Vocalization.

PMID- 20145216
TI  - A piece of my mind. The changing of the seasons.

PMID- 20145217
TI  - A piece of my mind. Coda: Don't touch me.

PMID- 20145218
TI  - Safety plan for opioids meets resistance: opioid-linked deaths continue to soar.

PMID- 20145219
TI  - New item on pediatric menu: food allergy.

PMID- 20145220
TI  - Hormone may play role in triggering panic attacks.

PMID- 20145221
TI  - Comparing endovascular and open repair of abdominal aortic aneurysm.

PMID- 20145222
TI  - Comparing endovascular and open repair of abdominal aortic aneurysm.

PMID- 20145223
TI  - Comparing endovascular and open repair of abdominal aortic aneurysm.

PMID- 20145224
TI  - High perioperative oxygen fraction for abdominal surgery and risk of surgical
      site infection.

PMID- 20145225
TI  - Association between CYP2D6 polymorphisms and breast cancer outcomes.

PMID- 20145226
TI  - Association between CYP2D6 polymorphisms and breast cancer outcomes.

PMID- 20145227
TI  - Clinical trial registration and publication of randomized controlled trials.

PMID- 20145228
TI  - Laparoscopic adjustable gastric banding in severely obese adolescents: a
      randomized trial.
AB  - CONTEXT: Adolescent obesity is a common and serious health problem affecting more
      than 5 million young people in the United States alone. Bariatric surgery is
      being evaluated as a possible treatment option. Laparoscopic adjustable gastric
      banding (gastric banding) has the potential to provide a safe and effective
      treatment. OBJECTIVE: To compare the outcomes of gastric banding with an optimal
      lifestyle program on adolescent obesity. DESIGN, SETTING, AND PATIENTS: A
      prospective, randomized controlled trial of 50 adolescents between 14 and 18
      years with a body mass index (BMI) higher than 35, recruited from the Melbourne,
      Australia, community, assigned either to a supervised lifestyle intervention or
      to undergo gastric banding, and followed up for 2 years. The study was performed
      between May 2005 and September 2008. MAIN OUTCOME MEASURES: Weight loss.
      Secondary outcomes included change in metabolic syndrome, insulin resistance,
      quality of life, and adverse outcomes. RESULTS: Twenty-four of 25 patients in the
      gastric banding group and 18 of 25 in lifestyle group completed the study. Twenty
      one (84%) in the gastric banding and 3 (12%) in the lifestyle groups lost more
      than 50% of excess weight, corrected for age. Overall, the mean changes in the
      gastric banding group were a weight loss of 34.6 kg (95% CI, 30.2-39.0),
      representing an excess weight loss of 78.8% (95% CI, 66.6%-91.0%), 12.7 BMI units
      (95% CI, 11.3-14.2), and a BMI z score change from 2.39 (95% CI, 2.05-2.73) to
      1.32 (95% CI, 0.98-1.66). The mean losses in the lifestyle group were 3.0 kg (95%
      CI, 2.1-8.1), representing excess weight loss of 13.2% (95% CI, 2.6%-21.0%), 1.3
      BMI units (95% CI, 0.4-2.9), and a BMI z score change from 2.41 (95% CI, 2.21
      2.66) to 2.26 (95% CI, 1.91-2.43). At entry, 9 participants (36%) in the gastric
      banding group and 10 (40%) in the lifestyle group had the metabolic syndrome. At
      24 months, none of the gastric banding group had the metabolic syndrome (P =
      .008; McNemar chi(2)) compared with 4 of the 18 completers (22%) in the lifestyle
      group (P = .13). The gastric banding group experienced improved quality of life
      with no perioperative adverse events. However, 8 operations (33%) were required
      in 7 patients for revisional procedures either for proximal pouch dilatation or
      tubing injury during follow-up. CONCLUSIONS: Among obese adolescent participants,
      use of gastric banding compared with lifestyle intervention resulted in a greater
      percentage achieving a loss of 50% of excess weight, corrected for age. There
      were associated benefits to health and quality of life. TRIAL REGISTRATION:
      ANZCTR Identifier: 12605000160639.

PMID- 20145229
TI  - Risk factors and outcomes associated with first-trimester fetal growth
      restriction.
AB  - CONTEXT: Adverse environmental exposures lead to developmental adaptations in
      fetal life. The influences of maternal physical characteristics and lifestyle
      habits on first-trimester fetal adaptations and the postnatal consequences are
      not known. OBJECTIVE: To determine the risk factors and outcomes associated with
      first-trimester growth restriction. DESIGN, SETTING, AND PARTICIPANTS:
      Prospective evaluation of the associations of maternal physical characteristics
      and lifestyle habits with first-trimester fetal crown to rump length in 1631
      mothers with a known and reliable first day of their last menstrual period and a
      regular menstrual cycle. Subsequently, we assessed the associations of first
      trimester fetal growth restriction with the risks of adverse birth outcomes and
      postnatal growth acceleration until the age of 2 years. The study was based in
      Rotterdam, The Netherlands. Mothers were enrolled between 2001 and 2005. MAIN
      OUTCOME MEASURES: First-trimester fetal growth was measured as fetal crown to
      rump length by ultrasound between the gestational age of 10 weeks 0 days and 13
      weeks 6 days. Main birth outcomes were preterm birth (gestational age <37 weeks),
      low birth weight (<2500 g), and small size for gestational age (lowest fifth
      birth centile). Postnatal growth was measured until the age of 2 years. RESULTS:
      In the multivariate analysis, maternal age was positively associated with first
      trimester fetal crown to rump length (difference per maternal year of age, 0.79
      mm; 95% confidence interval [CI], 0.41 to 1.18 per standard deviation score
      increase). Higher diastolic blood pressure and higher hematocrit levels were
      associated with a shorter crown to rump length (differences, -0.40 mm; 95% CI, 
      0.74 to -0.06 and -0.52 mm; 95% CI, -0.90 to -0.14 per standard deviation
      increase, respectively). Compared with mothers who were nonsmokers and optimal
      users of folic acid supplements, those who both smoked and did not use folic acid
      supplements had shorter fetal crown to rump lengths (difference, -3.84 mm; 95%
      CI, -5.71 to -1.98). Compared with normal first-trimester fetal growth, first
      trimester growth restriction was associated with increased risks of preterm birth
      (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 to 3.61), low birth
      weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 to 4.16), and small size
      for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 to
      4.25). Each standard deviation decrease in first-trimester fetal crown to rump
      length was associated with a postnatal growth acceleration until the age of 2
      years (standard deviation score increase, 0.139 per 2 years; 95% CI, 0.097 to
      0.181). CONCLUSIONS: Maternal physical characteristics and lifestyle habits were
      independently associated with early fetal growth. First-trimester fetal growth
      restriction was associated with an increased risk of adverse birth outcomes and
      growth acceleration in early childhood.

PMID- 20145230
TI  - Age- and sex-specific genomic profiles in non-small cell lung cancer.
AB  - CONTEXT: Gene expression profiling may be useful in examining differences
      underlying age- and sex-specific outcomes in non-small cell lung cancer (NSCLC).
      OBJECTIVE: To describe clinically relevant differences in the underlying biology
      of NSCLC based on patient age and sex. DESIGN, SETTING, AND PATIENTS:
      Retrospective analysis of 787 patients with predominantly early stage NSCLC
      performed at Duke University, Durham, North Carolina, from July 2008 to June
      2009. Lung tumor samples with corresponding microarray and clinical data were
      used. All patients were divided into subgroups based on age (< 70 vs > or = 70
      years old) or sex. Gene expression signatures representing oncogenic pathway
      activation and tumor biology/microenvironment status were applied to these
      samples to obtain patterns of activation/deregulation. MAIN OUTCOME MEASURES:
      Patterns of oncogenic and molecular signaling pathway activation that are
      reproducible and correlate with 5-year recurrence-free patient survival. RESULTS:
      Low- and high-risk patient clusters/cohorts were identified with the longest and
      shortest 5-year recurrence-free survival, respectively, within the age and sex
      NSCLC subgroups. These cohorts of NSCLC demonstrate similar patterns of pathway
      activation. In patients younger than 70 years, high-risk patients, with the
      shortest recurrence-free survival, demonstrated increased activation of the Src
      (25% vs 6%; P<.001) and tumor necrosis factor (76% vs 42%; P<.001) pathways
      compared with low-risk patients. High-risk patients aged 70 years or older
      demonstrated increased activation of the wound healing (40% vs 24%; P = .02) and
      invasiveness (64% vs 20%; P<.001) pathways compared with low-risk patients. In
      women, high-risk patients demonstrated increased activation of the invasiveness
      (99% vs 2%; P<.001) and STAT3 (72% vs 35%; P<.001) pathways while high-risk men
      demonstrated increased activation of the STAT3 (87% vs 18%; P<.001), tumor
      necrosis factor (90% vs 46%; P<.001), EGFR (13% vs 2%; P = .003), and wound
      healing (50% vs 22%; P<.001) pathways. Multivariate analyses confirmed the
      independent clinical relevance of the pathway-based subphenotypes in women
      (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.34-3.03; P<.001) and
      patients younger than 70 years (HR, 1.83; 95% CI, 1.24-2.71; P = .003). All
      observations were reproducible in split sample analyses. CONCLUSIONS: Among a
      cohort of patients with NSCLC, subgroups defined by oncogenic pathway activation
      profiles were associated with recurrence-free survival. These findings require
      validation in independent patient data sets.

PMID- 20145231
TI  - Hospital characteristics associated with feeding tube placement in nursing home
      residents with advanced cognitive impairment.
AB  - CONTEXT: Tube-feeding is of questionable benefit for nursing home residents with
      advanced dementia. Approximately two-thirds of US nursing home residents who are
      tube fed had their feeding tube inserted during an acute care hospitalization.
      OBJECTIVE: To identify US hospital characteristics associated with higher rates
      of feeding tube insertion in nursing home residents with advanced cognitive
      impairment. DESIGN, SETTING, AND PATIENTS: The sample included nursing home
      residents aged 66 years or older with advanced cognitive impairment admitted to
      acute care hospitals between 2000 and 2007. Rate of feeding tube placement was
      based on a 20% sample of all Medicare Claims files and was assessed in hospitals
      with at least 30 such admissions during the 8-year period. A multivariable model
      with the unit of the analysis being the hospital admission identified hospital
      level factors independently associated with feeding tube insertion rates,
      including bed size, ownership, urban location, and medical school affiliation.
      Measures of each hospital's care practices for all patients with serious chronic
      illnesses were evaluated, including intensive care unit (ICU) use in the last 6
      months of life, the use of hospice services, and the ratio of specialist to
      primary care physicians. Patient-level characteristics were also considered. MAIN
      OUTCOME MEASURE: Endoscopic or surgical insertion of a gastrostomy tube during a
      hospitalization. RESULTS: In 2797 acute care hospitals with 280,869 admissions
      among 163,022 nursing home residents with advanced cognitive impairment, the rate
      of feeding tube insertion varied from 0 to 38.9 per 100 hospitalizations (mean
      [SD], 6.5 [5.3]; median [interquartile range], 5.3 [2.6-9.3]). The mean rate of
      feeding tube insertions per 100 admissions was 7.9 in 2000, decreasing to 6.2 in
      2007. Higher insertion rates were associated with the following hospital
      features: for-profit ownership vs government owned (8.5 vs 5.5 insertions per 100
      hospitalizations; adjusted odds ratio [AOR], 1.33; 95% confidence interval [CI],
      1.21-1.46), larger size (>310 beds vs <101 beds: 8.0 vs 4.3 insertions per 100
      hospitalizations; AOR, 1.48; 95% CI, 1.35-1.63), and greater ICU use in the last
      6 months of life (highest vs lowest decile: 10.1 vs 2.9 insertions per 100
      hospitalizations; AOR, 2.60; 95% CI, 2.20-3.06). These differences persisted
      after controlling for patient characteristics. Specialist to primary care ratio
      and hospice use were weakly or not associated with feeding tube placement.
      CONCLUSION: Among nursing home residents with advanced cognitive impairment
      admitted to acute care hospitals, for-profit ownership, larger hospital size, and
      greater ICU use was associated with increased rates of feeding tube insertion,
      even after adjusting for patient-level characteristics.

PMID- 20145232
TI  - Perioperative beta-blockers for cardiac risk reduction: time for clarity.

PMID- 20145233
TI  - Enhancing the effectiveness of food labeling in restaurants.

PMID- 20145234
TI  - Replicating high-quality medical care organizations.

PMID- 20145235
TI  - Darwin's compassionate view of human nature.

PMID- 20145236
TI  - Surgical treatment of obesity in adolescence.

PMID- 20145237
TI  - First-trimester determination of complications of late pregnancy.

PMID- 20145238
TI  - JAMA patient page. Bariatric surgery.

PMID- 20145239
TI  - Loss of Dact1 disrupts planar cell polarity signaling by altering dishevelled
      activity and leads to posterior malformation in mice.
AB  - Wnt signaling plays a key role in embryogenesis and cancer development. Dvl
      (Dishevelled) is a central mediator for both the canonical and noncanonical Wnt
      pathways. Dact1 (Dapper1, Dpr1), a Dvl interactor, has been shown to negatively
      modulate Wnt signaling by promoting lysosomal degradation of Dvl. Here we report
      that Dact1-deficient mice have multiple physiological defects that resemble the
      human neonate disease congenital caudal regression syndrome, including caudal
      vertebrae agenesis, anorectal malformation, renal agenesis/dysplasia, fused
      kidneys, and loss of bladder. These urogenital defects can be traced to impaired
      hindgut formation starting at embryonic day 8.25. Examination of morphological
      changes and Wnt target gene expression revealed that the planar cell polarity
      (PCP) signaling is deregulated, whereas the canonical Wnt/beta-catenin pathway is
      largely unaffected in mutant embryos. Consistently, the activity of the PCP
      signal mediators Rho GTPase and c-Jun N-terminal kinase is altered in Dact1(-/-)
      mouse embryonic fibroblasts. We further observed alterations in the protein level
      and the cellular distribution of Dvl in the primitive streak of mutant embryos.
      An increased amount of Dvl2 tends to be accumulated in the cortical regions of
      the cells, especially at the primitive streak ectoderm close to the posterior
      endoderm that lately forms the hindgut diverticulum. Together, these data suggest
      that Dact1 may regulate vertebrate PCP by controlling the level and the cellular
      localization of Dvl protein.

PMID- 20145240
TI  - Drosophila stathmins bind tubulin heterodimers with high and variable
      stoichiometries.
AB  - In vertebrates, stathmins form a family of proteins possessing two tubulin
      binding repeats (TBRs), which each binds one soluble tubulin heterodimer. The
      stathmins thus sequester two tubulins in a phosphorylation-dependent manner,
      providing a link between signal transduction and microtubule dynamics. In
      Drosophila, we show here that a single stathmin gene (stai) encodes a family of D
      stathmin proteins. Two of the D-stathmins are maternally deposited and then
      restricted to germ cells, and the other two are detected in the nervous system
      during embryo development. Like in vertebrates, the nervous system-enriched
      stathmins contain an N-terminal domain involved in subcellular targeting. All the
      D-stathmins possess a domain containing three or four predicted TBRs, and we
      demonstrate here, using complementary biochemical and biophysical methods, that
      all four predicted TBR domains actually bind tubulin. D-stathmins can indeed bind
      up to four tubulins, the resulting complex being directly visualized by electron
      microscopy. Phylogenetic analysis shows that the presence of regulated multiple
      tubulin sites is a conserved characteristic of stathmins in invertebrates and
      allows us to predict key residues in stathmin for the binding of tubulin.
      Altogether, our results reveal that the single Drosophila stathmin gene codes for
      a stathmin family similar to the multigene vertebrate one, but with particular
      tubulin binding properties.

PMID- 20145241
TI  - Polyunsaturated fatty acids selectively suppress sterol regulatory element
      binding protein-1 through proteolytic processing and autoloop regulatory circuit.
AB  - Sterol regulatory element-binding protein (SREBP)-1 is a key transcription factor
      for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty
      acids (PUFA) selectively suppress hepatic SREBP-1, but molecular mechanisms
      remain largely unknown. To gain insight into this regulation, we established in
      vivo reporter assays to assess the activities of Srebf1c transcription and
      proteolytic processing. Using these in vivo reporter assays, we showed that the
      primary mechanism for PUFA suppression of SREBP-1 is at the proteolytic
      processing level and that this suppression in turn decreases the mRNA
      transcription through lowering SREBP-1 binding to the SREBP-binding element on
      the promoter ("autoloop regulatory circuit"), although liver X receptor, an
      activator for Srebf1c transcription, is not involved in this regulation by PUFA.
      The mechanisms for PUFA suppression of SREBP-1 confirm that the autoloop
      regulation for transcription is crucial for the nutritional regulation of
      triglyceride synthesis.

PMID- 20145242
TI  - Trypanosoma cruzi induces the reactive oxygen species-PARP-1-RelA pathway for up
      regulation of cytokine expression in cardiomyocytes.
AB  - In this study, we demonstrate that human cardiomyocytes (AC16) produce reactive
      oxygen species (ROS) and inflammatory cytokines in response to Trypanosoma cruzi.
      ROS were primarily produced by mitochondria, some of which diffused to cytosol of
      infected cardiomyocytes. These ROS resulted in an increase in 8-hydroxyguanine
      lesions and DNA fragmentation that signaled PARP-1 activation evidenced by
      poly(ADP-ribose) (PAR) modification of PARP-1 and other proteins in infected
      cardiomyocytes. Phenyl-alpha-tert-butylnitrone blocked the mitochondrial ROS
      (mtROS) formation, DNA damage, and PARP-1 activation in infected cardiomyocytes.
      Further inhibition studies demonstrated that ROS and PARP-1 signaled TNF-alpha
      and IL-1beta expression in infected cardiomyocytes. ROS directly signaled the
      nuclear translocation of RelA (p65), NF-kappaB activation, and cytokine gene
      expression. PARP-1 exhibited no direct interaction with p65 and did not signal
      its translocation to nuclei in infected cardiomyocytes. Instead, PARP-1
      contributed to PAR modification of p65-interacting nuclear proteins and assembly
      of the NF-kappaB transcription complex. PJ34 (PARP-1 inhibitor) also prevented
      mitochondrial poly(ADP-ribosyl)ation (PARylation) and ROS formation. We conclude
      that T. cruzi-mediated mtROS provide primary stimulus for PARP-1-NF-kappaB
      activation and cytokine gene expression in infected cardiomyocytes. PAR
      modification of mitochondrial membranes then results in a feedback cycle of mtROS
      formation and DNA damage/PARP-1 activation. ROS, either through direct modulation
      of cytosolic NF-kappaB, or via PARP-1-dependent PAR modification of p65
      interacting nuclear proteins, contributes to cytokine gene expression. Our
      results demonstrate a link between ROS and inflammatory responses in
      cardiomyocytes infected by T. cruzi and provide a clue to the pathomechanism of
      sustained inflammation in Chagas disease.

PMID- 20145243
TI  - Gentisic acid, a compound associated with plant defense and a metabolite of
      aspirin, heads a new class of in vivo fibroblast growth factor inhibitors.
AB  - Fibroblast growth factors are key proteins in many intercellular signaling
      networks. They normally remain attached to the extracellular matrix, which
      confers on them a considerable stability. The unrestrained accumulation of
      fibroblast growth factors in the extracellular milieu, either due to uncontrolled
      synthesis or enzymatic release, contributes to the pathology of many diseases.
      Consequently, the neutralization of improperly mobilized fibroblast growth
      factors is of clear therapeutic interest. In pursuing described rules to identify
      potential inhibitors of these proteins, gentisic acid, a plant pest-controlling
      compound, an aspirin and vegetarian diet common catabolite, and a component of
      many traditional liquors and herbal remedies, was singled out as a powerful
      inhibitor of fibroblast growth factors. Gentisic acid was used as a lead to
      identify additional compounds with better inhibitory characteristics generating a
      new chemical class of fibroblast growth factor inhibitors that includes the agent
      responsible for alkaptonuria. Through low and high resolution approaches, using
      representative members of the fibroblast growth factor family and their cell
      receptors, it was shown that this class of inhibitors may employ two different
      mechanisms to interfere with the assembly of the signaling complexes that trigger
      fibroblast growth factor-driven mitogenesis. In addition, we obtained evidence
      from in vivo disease models that this group of inhibitors may be of interest to
      treat cancer and angiogenesis-dependent diseases.

PMID- 20145244
TI  - Histone deacetylase inhibitor valproic acid inhibits cancer cell proliferation
      via down-regulation of the alzheimer amyloid precursor protein.
AB  - The beta-amyloid precursor protein (APP) represents a type I transmembrane
      glycoprotein that is ubiquitously expressed. In the brain, it is a key player in
      the molecular pathogenesis of Alzheimer disease. Its physiological function is
      however less well understood. Previous studies showed that APP is up-regulated in
      prostate, colon, pancreatic tumor, and oral squamous cell carcinoma. In this
      study, we show that APP has an essential role in growth control of pancreatic and
      colon cancer. Abundant APP staining was found in human pancreatic adenocarcinoma
      and colon cancer tissue. Interestingly, treating pancreatic and colon cancer
      cells with valproic acid (VPA, 2-propylpentanoic acid), a known histone
      deacetylase (HDAC) inhibitor, leads to up-regulation of GRP78, an endoplasmic
      reticulum chaperone immunoglobulin-binding protein. GRP78 is involved in APP
      maturation and inhibition of tumor cell growth by down-regulation of APP and
      secreted soluble APPalpha. Trichostatin A, a pan-HDAC inhibitor, also lowered APP
      and increased GRP78 levels. In contrast, treating cells with valpromide, a VPA
      derivative lacking HDAC inhibitory properties, had no effect on APP levels. VPA
      did not modify the level of epidermal growth factor receptor, another type I
      transmembrane protein, and APLP2, a member of the APP family, demonstrating the
      specificity of the VPA effect on APP. Small interfering RNA-mediated knockdown of
      APP also resulted in significantly decreased cell growth. Based on these
      observations, the data suggest that APP down-regulation via HDAC inhibition
      provides a novel mechanism for pancreatic and colon cancer therapy.

PMID- 20145245
TI  - Peroxiredoxin Ahp1 acts as a receptor for alkylhydroperoxides to induce disulfide
      bond formation in the Cad1 transcription factor.
AB  - Reactive oxygen species (ROS) generated during cellular metabolism are toxic to
      cells. As a result, cells must be able to identify ROS as a stress signal and
      induce stress response pathways that protect cells from ROS toxicity. Recently,
      peroxiredoxin (Prx)-induced relays of disulfide bond formation have been
      identified in budding yeast, namely the disulfide bond formation of Yap1, a
      crucial transcription factor for oxidative stress response, by a specific Prx
      Gpx3 and by a major Prx Tsa1. Here, we show that an atypical-type Prx Ahp1 can
      act as a receptor for alkylhydroperoxides, resulting in activation of the Cad1
      transcription factor that is homologous to Yap1. We demonstrate that Ahp1 is
      required for the formation of intermolecular Cad1 disulfide bond(s) in both an in
      vitro redox system and in cells treated with alkylhydroperoxide. Furthermore, we
      found that Cad1-dependent transcriptional activation of the HSP82 gene is
      dependent on Ahp1. Our results suggest that, although the Gpx3-Yap1 pathway
      contributes more strongly to resistance than the Ahp1-Cad1 pathway, the Ahp1
      induced activation of Cad1 can function as a defense system against stress
      induced by alkylhydroperoxides, possibly including lipid peroxides. Thus, the Prx
      family of proteins have an important role in determining peroxide response
      signals and in transmitting the signals to specific target proteins by inducing
      disulfide bond formation.

PMID- 20145246
TI  - Aph-1 associates directly with full-length and C-terminal fragments of gamma
      secretase substrates.
AB  - Gamma-secretase is a ubiquitous, multiprotein enzyme composed of presenilin,
      nicastrin, Aph-1, and Pen-2. It mediates the intramembrane proteolysis of many
      type 1 proteins, plays an essential role in numerous signaling pathways, and
      helps drive the pathogenesis of Alzheimer disease by excising the hydrophobic,
      aggregation-prone amyloid beta-peptide from the beta-amyloid precursor protein. A
      central unresolved question is how its many substrates bind and enter the gamma
      secretase complex. Here, we provide evidence that both the beta-amyloid precursor
      protein holoprotein and its C-terminal fragments, the immediate substrates of
      gamma-secretase, can associate with Aph-1 at overexpressed as well as endogenous
      protein levels. This association was observed using bi-directional co
      immunoprecipitation in multiple systems and detergent conditions, and an beta
      amyloid precursor protein-Aph-1 complex was specifically isolated following in
      situ cross-linking in living cells. In addition, another endogenous canonical
      gamma-substrate, Jagged, showed association of both its full-length and C
      terminal fragment forms with Aph-1. We were also able to demonstrate that this
      interaction with substrates was conserved across the multiple isoforms of Aph-1
      (beta, alphaS, and alphaL), as they were all able to bind beta-amyloid precursor
      protein with similar affinity. Finally, two highly conserved intramembrane
      histidines (His-171 and His-197) within Aph-1, which were recently shown to be
      important for gamma-secretase activity, are required for efficient binding of
      substrates. Taken together, our data suggest a dominant role for Aph-1 in
      interacting with gamma-secretase substrates prior to their processing by the
      proteolytic complex.

PMID- 20145247
TI  - Myosin cross-reactive antigen of Streptococcus pyogenes M49 encodes a fatty acid
      double bond hydratase that plays a role in oleic acid detoxification and
      bacterial virulence.
AB  - The myosin cross-reactive antigen (MCRA) protein family is highly conserved among
      different bacterial species ranging from Gram-positive to Gram-negative bacteria.
      Besides their ubiquitous occurrence, knowledge about the biochemical and
      physiological function of MCRA proteins is scarce. Here, we show that MCRA
      protein from Streptococcus pyogenes M49 is a FAD enzyme, which acts as hydratase
      on (9Z)- and (12Z)-double bonds of C-16, C-18 non-esterified fatty acids.
      Products are 10-hydroxy and 10,13-dihydroxy fatty acids. Kinetic analysis
      suggests that FAD rather stabilizes the active conformation of the enzyme and is
      not directly involved in catalysis. Analysis of S. pyogenes M49 grown in the
      presence of either oleic or linoleic acid showed that 10-hydroxy and 10,13
      dihydroxy derivatives were the only products. No further metabolism of these
      hydroxy fatty acids was detected. Deletion of the hydratase gene caused a 2-fold
      decrease in minimum inhibitory concentration against oleic acid but increased
      survival of the mutant strain in whole blood. Adherence and internalization
      properties to human keratinocytes were reduced in comparison with the wild type.
      Based on these results, we conclude that the previously identified MCRA protein
      can be classified as a FAD-containing double bond hydratase, within the carbon
      oxygen lyase family, that plays a role in virulence of at least S. pyogenes M49.

PMID- 20145248
TI  - Distinct modulations of human capsaicin receptor by protons and magnesium through
      different domains.
AB  - The capsaicin receptor (TRPV1) is a nonselective cation channel that integrates
      multiple painful stimuli, including capsaicin, protons, and heat. Protons
      facilitate the capsaicin- and heat-induced currents by decreasing thermal
      threshold or increasing agonist potency for TRPV1 activation (Tominaga, M.,
      Caterina, M. J., Malmberg, A. B., Rosen, T. A., Gilbert, H., Skinner, K.,
      Raumann, B. E., Basbaum, A. I., and Julius, D. (1998) Neuron 21, 531-543). In the
      presence of saturating capsaicin, rat TRPV1 (rTRPV1) reaches full activation,
      with no further stimulation by protons. Human TRPV1 (hTRPV1), a species ortholog
      with high homology to rTRPV1, is potentiated by extracellular protons and
      magnesium, even at saturating capsaicin. We investigated the structural basis for
      protons and magnesium modulation of fully capsaicin-bound human receptors. By
      analysis of chimeric channels between hTRPV1 and rTRPV1, we found that
      transmembrane domain 1-4 (TM1-4) of TRPV1 determines whether protons can further
      open the fully capsaicin-bound receptors. Mutational analysis identified a
      titratable glutamate residue (Glu-536) in the linker between TM3 and TM4 critical
      for further stimulation of fully liganded hTRPV1. In contrast, hTRPV1 TM5-6 is
      required for magnesium augmentation of capsaicin efficacy. Our results
      demonstrate that capsaicin efficacy of hTRPV1 correlates with the extracellular
      ion milieu and unravel the relevant structural basis of modulation by protons and
      magnesium.

PMID- 20145249
TI  - Atypical alpha-conotoxin LtIA from Conus litteratus targets a novel microsite of
      the alpha3beta2 nicotinic receptor.
AB  - Different nicotinic acetylcholine receptor (nAChR) subtypes are implicated in
      learning, pain sensation, and disease states, including Parkinson disease and
      nicotine addiction. alpha-Conotoxins are among the most selective nAChR ligands.
      Mechanistic insights into the structure, function, and receptor interaction of
      alpha-conotoxins may serve as a platform for development of new therapies.
      Previously characterized alpha-conotoxins have a highly conserved Ser-Xaa-Pro
      motif that is crucial for potent nAChR interaction. This study characterized the
      novel alpha-conotoxin LtIA, which lacks this highly conserved motif but potently
      blocked alpha3beta2 nAChRs with a 9.8 nm IC(50) value. The off-rate of LtIA was
      rapid relative to Ser-Xaa-Pro-containing alpha-conotoxin MII. Nevertheless, pre
      block of alpha3beta2 nAChRs with LtIA prevented the slowly reversible block
      associated with MII, suggesting overlap in their binding sites. nAChR beta
      subunit ligand-binding interface mutations were used to examine the >1000-fold
      selectivity difference of LtIA for alpha3beta2 versus alpha3beta4 nAChRs. Unlike
      MII, LtIA had a >900-fold increased IC(50) value on alpha3beta2(F119Q) versus
      wild type nAChRs, whereas T59K and V111I beta2 mutants had little effect.
      Molecular docking simulations suggested that LtIA had a surprisingly shallow
      binding site on the alpha3beta2 nAChR that includes beta2 Lys-79. The K79A mutant
      disrupted LtIA binding but was without effect on an LtIA analog where the Ser-Xaa
      Pro motif is present, consistent with distinct binding modes.

PMID- 20145250
TI  - Terpestacin inhibits tumor angiogenesis by targeting UQCRB of mitochondrial
      complex III and suppressing hypoxia-induced reactive oxygen species production
      and cellular oxygen sensing.
AB  - Cellular oxygen sensing is required for hypoxia-inducible factor-1alpha
      stabilization, which is important for tumor cell survival, proliferation, and
      angiogenesis. Here we find that terpestacin, a small molecule previously
      identified in a screen of microbial extracts, binds to the 13.4-kDa subunit
      (UQCRB) of mitochondrial Complex III, resulting in inhibition of hypoxia-induced
      reactive oxygen species generation. Consequently, such inhibition blocks hypoxia
      inducible factor activation and tumor angiogenesis in vivo, without inhibiting
      mitochondrial respiration. Overexpression of UQCRB or its suppression using RNA
      interference demonstrates that it plays a crucial role in the oxygen sensing
      mechanism that regulates responses to hypoxia. These findings provide a novel
      molecular basis of terpestacin targeting UQCRB of Complex III in selective
      suppression of tumor progression.

PMID- 20145251
TI  - Adipocyte fatty acid-binding protein modulates inflammatory responses in
      macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases
      and activator protein-1.
AB  - Adipocyte fatty acid-binding protein (A-FABP) has emerged as an important
      mediator of inflammation in macrophages. Macrophage-selective ablation of A-FABP
      alone is sufficient to prevent the development of high cholesterol diet-induced
      atherosclerosis in apoE-deficient mice. However, the precise mechanisms whereby A
      FABP modulates inflammation remain elusive. Here, we report that A-FABP forms a
      finely tuned positive loop between JNK and activator protein-1 (AP-1) to
      exacerbate lipopolysaccharide (LPS)-induced inflammatory responses in
      macrophages. Real time PCR and luciferase reporter analysis showed that LPS
      induced A-FABP expression through transcriptional activation. This effect was
      mediated by JNK, which promoted the recruitment of c-Jun to a highly conserved AP
      1 consensus binding motif located within the proximal region of the A-FABP
      promoter. LPS-induced transactivation of the A-FABP gene was diminished by either
      pharmacological inhibition of JNK or knocking down c-Jun or by mutating the AP-1
      recognition site within the proximal region (-122 to -116 bp) of the A-FABP
      promoter. Conversely, the LPS-evoked phosphorylation of JNK, activation of AP-1,
      and production of pro-inflammatory cytokines were markedly attenuated by
      pharmacological or genetic suppression of A-FABP in macrophages. Furthermore, the
      LPS-induced elevation in A-FABP expression could also be prevented by the
      selective A-FABP inhibitor BMS309403. These findings support the notion that
      pharmacological inhibition of A-FABP represents a valid strategy for treating
      inflammation-related disorders such as atherosclerosis.

PMID- 20145252
TI  - Phosphorylation of yeast phosphatidylserine synthase by protein kinase A:
      identification of Ser46 and Ser47 as major sites of phosphorylation.
AB  - The CHO1-encoded phosphatidylserine synthase from Saccharomyces cerevisiae is
      phosphorylated and inhibited by protein kinase A in vitro. CHO1 alleles bearing
      Ser(46) --> Ala and/or Ser(47) --> Ala mutations were constructed and expressed
      in a cho1Delta mutant lacking phosphatidylserine synthase. In vitro, the
      S46A/S47A mutation reduced the total amount of phosphorylation by 90% and
      abolished the inhibitory effect protein kinase A had on phosphatidylserine
      synthase activity. The enzyme phosphorylation by protein kinase A, which was time
      and dose-dependent and dependent on the concentration of ATP, caused a
      electrophoretic mobility shift from a 27-kDa form to a 30-kDa form. The two
      electrophoretic forms of phosphatidylserine synthase were present in exponential
      phase cells, whereas only the 27-kDa form was present in stationary phase cells.
      In vivo labeling with (32)P(i) and immune complex analysis showed that the 30-kDa
      form was predominantly phosphorylated when compared with the 27-kDa form.
      However, the S46A/S47A mutations abolished the protein kinase A-mediated
      electrophoretic mobility shift. The S46A/S47A mutations also caused a 55%
      reduction in the total amount of phosphatidylserine synthase in exponential phase
      cells and a 66% reduction in the amount of enzyme in stationary phase cells. In
      phospholipid composition analysis, cells expressing the S46A/S47A mutant enzyme
      exhibited a 57% decrease in phosphatidylserine and a 40% increase in
      phosphatidylinositol. These results indicate that phosphatidylserine synthase is
      phosphorylated on Ser(46) and Ser(47) by protein kinase A, which results in a
      higher amount of enzyme for the net effect of stimulating the synthesis of
      phosphatidylserine.

PMID- 20145253
TI  - Mutant huntingtin in glial cells exacerbates neurological symptoms of Huntington
      disease mice.
AB  - Huntington disease (HD) is caused by an expansion of the polyglutamine (polyQ)
      repeat (>37Q) in huntingtin (htt), and age of onset is inversely correlated with
      the length of the polyQ repeat. Mutant htt with expanded polyQ is ubiquitously
      expressed in various types of cells, including glia, but causes selective
      neurodegeneration. Our recent study demonstrated that expression of the N
      terminal mutant htt with a large polyQ repeat (160Q) in astrocytes is sufficient
      to induce neurological symptoms in mice (Bradford, J., Shin, J. Y., Roberts, M.,
      Wang, C. E., Li, X.-J., and Li, S. H. (2009) Proc. Natl. Acad. Sci. U.S.A. 106,
      22480-22485). Because glia-neuron interactions are critical for maintaining the
      normal function and survival of neurons in the brain and because mutant htt is
      more abundant in neurons than in glial cells, it is important to investigate
      whether glial htt can still contribute to HD pathology when mutant htt is
      abundantly expressed in neuronal cells. We generated transgenic mice that express
      mutant htt with 98Q in astrocytes. Unlike our recently generated htt-160Q
      transgenic mice, htt-98Q mice do not show obvious neurological phenotypes,
      suggesting that the length of the polyQ repeat determines the severity of glial
      dysfunction. However, htt-98Q mice show increased susceptibility to glutamate
      induced seizure. Mice expressing mutant htt in astrocytes were mated with N171
      82Q mice that express mutant htt primarily in neuronal cells. Double transgenic
      mice expressing mutant htt in both neuronal and glial cells display more severe
      neurological symptoms and earlier death than N171-82Q mice. These findings
      indicate a role of glial mutant htt in exacerbating HD neuropathology and
      underscore the importance of improving glial function in treating HD.

PMID- 20145254
TI  - Mechanistic differences between two conserved classes of small heat shock
      proteins found in the plant cytosol.
AB  - The small heat shock proteins (sHSPs) and alpha-crystallins are highly effective,
      ATP-independent chaperones that can bind denaturing client proteins to prevent
      their irreversible aggregation. One model of sHSP function suggests that the
      oligomeric sHSPs are activated to the client-binding form by dissociation at
      elevated temperatures to dimers or other sub-oligomeric species. Here we examine
      this model in a comparison of the oligomeric structure and chaperone activity of
      two conserved classes of cytosolic sHSPs in plants, the class I (CI) and class II
      (CII) proteins. Like the CI sHSPs, recombinant CII sHSPs from three divergent
      plant species, pea, wheat, and Arabidopsis, are dodecamers as determined by nano
      electrospray mass spectrometry. While at 35 to 45 degrees C, all three CI sHSPs
      reversibly dissociate to dimers, the CII sHSPs retain oligomeric structure at
      high temperature. The CII dodecamers are, however, dynamic and rapidly exchange
      subunits, but unlike CI sHSPs, the exchange unit appears larger than a dimer.
      Differences in dodecameric structure are also reflected in the fact that the CII
      proteins do not hetero-oligomerize with CI sHSPs. Binding of the hydrophobic
      probe bis-ANS and limited proteolysis demonstrate CII proteins undergo
      significant, reversible structural changes at high temperature. All three
      recombinant CII proteins more efficiently protect firefly luciferase from
      insolubilization during heating than do the CI proteins. The CI and CII proteins
      behave strictly additively in client protection. In total, the results
      demonstrate that different sHSPs can achieve effective protection of client
      proteins by varied mechanisms.

PMID- 20145255
TI  - Characterization of the human insulin-induced gene 2 (INSIG2) promoter: the role
      of Ets-binding motifs.
AB  - Insulin-induced gene 2 (INSIG2) and its homolog INSIG1 encode closely related
      endoplasmic reticulum proteins that regulate the proteolytic activation of sterol
      regulatory element-binding proteins, transcription factors that activate the
      synthesis of cholesterol and fatty acids in animal cells. Several studies have
      been carried out to identify INSIG2 genetic variants associated with metabolic
      diseases. However, few data have been published regarding the regulation of
      INSIG2 gene expression. Two Insig2 transcripts have been described in rodents
      through the use of different promoters that produce different noncoding first
      exons that splice into a common second exon. Herein we report the cloning and
      characterization of the human INSIG2 promoter and the detection of an INSIG2
      specific transcript homologous to the Insig2b mouse variant in human liver.
      Deletion analyses on 3 kb of 5'-flanking DNA of the human INSIG2 gene revealed
      the functional importance of a 350-bp region upstream of the transcription start
      site. Mutated analyses, chromatin immunoprecipitation assays, and RNA
      interference analyses unveiled the significance of an Ets-consensus motif in the
      proximal region and the interaction of the Ets family member SAP1a (serum
      response factor (SRF) accessory protein-1a) with this region of the human INSIG2
      promoter. Moreover, our findings suggest that insulin activated the human INSIG2
      promoter in a process mediated by phosphorylated SAP1a. Overall, these results
      map the functional elements in the human INSIG2 promoter sequence and suggest an
      unexpected regulation of INSIG2 gene expression in human liver.

PMID- 20145256
TI  - Glucagon-like peptide-1 increases beta-cell glucose competence and proliferation
      by translational induction of insulin-like growth factor-1 receptor expression.
AB  - Glucagon-like peptide-1 (GLP-1) protects beta-cells against apoptosis, increases
      their glucose competence, and induces their proliferation. We previously
      demonstrated that the anti-apoptotic effect was mediated by an increase in
      insulin-like growth factor-1 receptor (IGF-1R) expression and signaling, which
      was dependent on autocrine secretion of insulin-like growth factor 2 (IGF-2).
      Here, we further investigated how GLP-1 induces IGF-1R expression and whether the
      IGF-2/IGF-1R autocrine loop is also involved in mediating GLP-1-increase in
      glucose competence and proliferation. We show that GLP-1 up-regulated IGF-1R
      expression by a protein kinase A-dependent translational control mechanism,
      whereas isobutylmethylxanthine, which led to higher intracellular accumulation of
      cAMP than GLP-1, increased both IGF-1R transcription and translation. We then
      demonstrated, using MIN6 cells and primary islets, that the glucose competence of
      these cells was dependent on the level of IGF-1R expression and on IGF-2
      secretion. We showed that GLP-1-induced primary beta-cell proliferation was
      suppressed by Igf-1r gene inactivation and by IGF-2 immunoneutralization or
      knockdown. Together our data show that regulation of beta-cell number and
      function by GLP-1 depends on the cAMP/protein kinase A mediated-induction of IGF
      1R expression and the increased activity of an IGF-2/IGF-1R autocrine loop.

PMID- 20145258
TI  - Variability in free mycophenolic acid exposure in adult liver transplant
      recipients during the early posttransplantation period.
AB  - Mycophenolate mofetil (MMF) pharmacokinetics variability in liver transplant
      recipients during the early posttransplantation period may be related to changes
      in mycophenolic acid (MPA) protein binding. This study aimed at characterizing
      the variation of free MPA exposure with respect to time since transplantation.
      Three groups (A, B, C) were compared. The median posttransplantation time was 12
      days (A, n = 26 pharmacokinetic sessions), 36 days (B, n = 25), and 867 days (C,
      n = 21). The median MPA AUC(0-12) in group A (26.8 mg x h/L) was significantly
      lower than in groups B (45.2 mg x h/L, P = .031) and C (43.5 mg x h/L, P = .004).
      Free MPA AUC(0-12) was comparable whatever the time (0.41, 0.34, and 0.33 mg x
      h/L, respectively). MPA apparent clearance (CL/F) was significantly correlated
      with MPA free fraction (r = 0.60, P < .0001) and approximately 1.7-fold higher in
      group A compared to groups B and C (P < .05). Enhanced CL/F in relation with an
      increase in MPA free fraction results in a low AUC of total MPA during the first
      postoperative month, but on average, at the population level, the exposure to
      free MPA is not altered, suggesting that total MPA AUC should not be used to
      adapt MMF dosing during this period.

PMID- 20145257
TI  - Very-long-chain fatty acids are involved in polar auxin transport and
      developmental patterning in Arabidopsis.
AB  - Very-long-chain fatty acids (VLCFAs) are essential for many aspects of plant
      development and necessary for the synthesis of seed storage triacylglycerols,
      epicuticular waxes, and sphingolipids. Identification of the acetyl-CoA
      carboxylase PASTICCINO3 and the 3-hydroxy acyl-CoA dehydratase PASTICCINO2
      revealed that VLCFAs are important for cell proliferation and tissue patterning.
      Here, we show that the immunophilin PASTICCINO1 (PAS1) is also required for VLCFA
      synthesis. Impairment of PAS1 function results in reduction of VLCFA levels that
      particularly affects the composition of sphingolipids, known to be important for
      cell polarity in animals. Moreover, PAS1 associates with several enzymes of the
      VLCFA elongase complex in the endoplasmic reticulum. The pas1 mutants are
      deficient in lateral root formation and are characterized by an abnormal
      patterning of the embryo apex, which leads to defective cotyledon organogenesis.
      Our data indicate that in both tissues, defective organogenesis is associated
      with the mistargeting of the auxin efflux carrier PIN FORMED1 in specific cells,
      resulting in local alteration of polar auxin distribution. Furthermore, we show
      that exogenous VLCFAs rescue lateral root organogenesis and polar auxin
      distribution, indicating their direct involvement in these processes. Based on
      these data, we propose that PAS1 acts as a molecular scaffold for the fatty acid
      elongase complex in the endoplasmic reticulum and that the resulting VLCFAs are
      required for polar auxin transport and tissue patterning during plant
      development.

PMID- 20145259
TI  - Clinical pharmacokinetics of laninamivir, a novel long-acting neuraminidase
      inhibitor, after single and multiple inhaled doses of its prodrug, CS-8958, in
      healthy male volunteers.
AB  - Phase 1 studies of laninamivir, a novel long-acting neuraminidase inhibitor, were
      carried out to assess its safety, tolerability, and pharmacokinetics after
      inhaled administration of its prodrug, CS-8958. Healthy male volunteers (total N
      = 76) participated in double-blind, randomized, placebo-controlled trials and
      received 5, 10, 20, 40, 80, or 120 mg of a single dose or 20 or 40 mg of a twice
      daily dose for 3 days. The clinical and laboratory parameters and plasma and
      urinary concentrations of CS-8958 and laninamivir for 144 hours post dosing were
      measured. There were no adverse events related to the test drug. CS-8958
      disappeared from plasma with a half-life of about 2 hours, although laninamivir
      was slowly eliminated from the body, lasting for even up to 144 hours after
      administration with a half-life of about 3 days. Area under the curve and maximum
      concentration increased almost linearly with the dose administered. The
      cumulative urinary excretion amounts of CS-8958 and laninamivir were 2.3% to 3.6%
      and 10.7% to 14.6% of the dose, respectively. The half-life of the urinary
      excretion rates of laninamivir at higher single dose is comparable to plasma half
      life. CS-8958, when inhaled by healthy volunteers, is well tolerated and exhibits
      a suitable pharmacokinetic profile, suggesting potential for long-lasting anti
      influenza activity.

PMID- 20145260
TI  - Pharmacokinetics and pharmacodynamics of three moxifloxacin dosage forms:
      implications for blinding in active-controlled cardiac repolarization studies.
AB  - Moxifloxacin is used in thorough QT studies to assess sensitivity for detection
      of an increase in QTc. Moxifloxacin is usually over-encapsulated for blinding.
      However, there is concern that over-encapsulation alters its pharmacokinetics. In
      a 4-arm, randomized crossover study, 22 volunteers received over-encapsulated
      moxifloxacin, over-encapsulated placebo, bare moxifloxacin, and intravenous (IV)
      moxifloxacin. Placebo capsules and IV infusions were administered so that
      treatments in each arm, except for bare moxifloxacin, were indistinguishable.
      Pharmacokinetics of the oral treatments were found to be nearly identical and to
      meet Food and Drug Administration criteria for bioequivalency. Relative to the IV
      infusion administered over 1 hour, the tablet formulation was bioequivalent to
      total exposure but not peak exposure maximum plasma concentration, which was
      lower by 22%. Median time to maximum plasma concentration of the IV infusion was
      1.00 hour. A 2-compartment model with oral absorption and linear elimination
      adequately described the observed moxifloxacin data. Changes in QTcF mirrored the
      pharmacokinetic changes, and there was a linear relationship between plasma
      concentration of moxifloxacin and change in QTcF. A 2-stage infusion scheme for
      IV moxifloxacin mimics the oral plasma concentration versus time curve. Over
      encapsulation of moxifloxacin did not alter its peak or total systemic exposures
      or pharmacodynamics after oral administration.

PMID- 20145261
TI  - Comparison of the gastrointestinal absorption and bioavailability of fenofibrate
      and fenofibric acid in humans.
AB  - This study compared the gastrointestinal (GI) absorption characteristics and
      absolute bioavailability of fenofibric acid and fenofibrate (which is converted
      to fenofibric acid in vivo) in healthy volunteers. Treatments were delivered to
      the proximal small bowel, distal small bowel, and colon using a site-specific
      delivery system (Enterion capsule) and to the stomach by oral administration of
      equimolar doses. Serial blood samples were collected for 120 hours postdose and
      assayed for plasma fenofibric acid concentrations. The absolute bioavailability
      of each treatment was determined relative to 50 mg of fenofibric acid
      administered intravenously. Plasma exposure to fenofibric acid following
      fenofibric acid administration was approximately 1.5 times higher than that
      following fenofibrate administration for delivery to the proximal and distal
      small bowel and following oral administration, and it was approximately 5 times
      higher following colon delivery. The absolute bioavailability in the stomach,
      proximal small bowel, distal small bowel, and colon was approximately 81%, 88%,
      84%, and 78%, respectively, for fenofibric acid and 69%, 73%, 66%, and 22%,
      respectively, for fenofibrate (P < .0001 and P = .033 for fenofibric acid vs
      fenofibrate in the colon and distal small bowel, respectively). In conclusion,
      fenofibric acid is well absorbed throughout the GI tract and has greater
      bioavailability than fenofibrate in all GI regions.

PMID- 20145262
TI  - Pharmacokinetics, pharmacodynamics, and metabolism of triethylenetetramine in
      healthy human participants: an open-label trial.
AB  - The selective Cu(II)-chelator, triethylenetetramine (TETA), is undergoing
      clinical trials for the treatment of heart failure in patients with diabetes.
      Recently, the authors showed that 2 acetylated metabolites, N(1)
      acetyltriethylenetetramine (MAT) and N(1),N(10)-diacetyltriethylenetetramine
      (DAT), are formed in humans following oral TETA administration. Thus, it became
      necessary to determine whether the N-acetyltransferase (NAT) 2 phenotype has any
      effects on the pharmacological properties and safety profile of TETA. Twelve fast
      and 12 slow NAT2-phenotype healthy participants were recruited. After oral drug
      administration, the authors collected plasma and urine samples, measured plasma
      concentrations of TETA and its 2 metabolites along with concomitant urinary
      copper concentrations, and performed safety tests. They present, for the first
      time, the complete 24-hour pharmacokinetic profiles of TETA, MAT, and DAT in
      humans. There was no evidence for clear-cut differences in pharmacokinetic
      profiles between fast and slow acetylators. Pharmacodynamic analysis showed no
      significant differences in cupruresis between the 2 NAT2 phenotypes. Safety
      results were consistent with TETA being well tolerated, and no significant
      differences in safety profiles were observed between the 2 phenotypes. Based on
      these data, NAT2 phenotype does not affect TETA's pharmacokinetic,
      pharmacodynamic, or safety profiles. TETA may be acetylated via an alternative
      mechanism, such as that catalyzed by spermidine/spermine N(1)-acetyltranferase.

PMID- 20145263
TI  - Atenolol pharmacokinetics and excretion in breast milk during the first 6 to 8
      months postpartum.
AB  - The objectives were to evaluate the time course for atenolol pharmacokinetics in
      lactating women postpartum and to quantify atenolol plasma concentrations in the
      women's 3- to 4-month-old nursing infants. Data were collected during 1 dosing
      interval from lactating women treated with atenolol for therapeutic reasons, at 2
      to 4 weeks (n = 32), 3 to 4 months (n = 22), and 6 to 8 months (n = 17)
      postpartum. A single blood sample was collected from 15 nursing infants (3-4
      months of age) of the mothers participating in the study. At 2 to 4 weeks, 3 to 4
      months, and 6 to 8 months postpartum, atenolol infant doses, relative to the
      mother's weight-adjusted dose, were 14.6% +/- 7.6%, 8.3% +/- 5.2% and 5.9% +/-
      2.9%, respectively. Over this time, maternal atenolol pharmacokinetics did not
      change to a clinically significant extent. Atenolol concentrations were below
      assay quantification limits (<10 ng/mL) in the plasma of all 3- to 4-month-old
      nursing infants studied. These findings support the careful use of atenolol
      during breastfeeding, because in the vast majority of healthy, term infants,
      atenolol concentrations will be too low to be clinically relevant. Premature
      infants and those with kidney disease require further study. Infant exposure
      depends on maternal dose and decreases during the first 6 to 8 months postpartum.

PMID- 20145264
TI  - CXCL12-induced chemotaxis is impaired in T cells from patients with ZAP-70
      negative chronic lymphocytic leukemia.
AB  - BACKGROUND: T cells from patients with chronic lymphocytic leukemia may play an
      important role in contributing to the onset, sustenance, and exacerbation of the
      disease by providing survival and proliferative signals to the leukemic clone
      within lymph nodes and bone marrow. DESIGN AND METHODS: By performing chemotaxis
      assays towards CXCL12, CCL21 and CCL19, we sought to evaluate the migratory
      potential of T cells from chronic lymphocytic leukemia patients. We next analyzed
      the chemokine-induced migration of T cells, dividing the chronic lymphocytic
      leukemia samples according to their expression of the poor prognostic factors
      CD38 and ZAP-70 in leukemic cells determined by flow cytometry. RESULTS: We found
      that T cells from patients with chronic lymphocytic leukemia are less responsive
      to CXCL12, CCL21 and CCL19 than T cells from healthy adults despite similar CXCR4
      and CCR7 expression. Following separation of the patients into two groups
      according to ZAP-70 expression, we found that T cells from ZAP-70-negative
      samples showed significantly less migration towards CXCL12 compared to T cells
      from ZAP-70-positive samples and that this was not due to defective CXCR4 down
      regulation, F-actin polymerization or to a lesser expression of ZAP-70, CD3,
      CD45, CD38 or CXCR7 on these cells. Interestingly, we found that leukemic cells
      from ZAP-70-negative samples seem to be responsible for the defective CXCR4
      migratory response observed in their T cells. CONCLUSIONS: Impaired migration
      towards CXCL12 may reduce the access of T cells from ZAP-70-negative patients to
      lymphoid organs, creating a less favorable microenvironment for leukemic cell
      survival and proliferation.

PMID- 20145265
TI  - Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal
      hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3
      opsonization.
AB  - BACKGROUND: Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia
      characterized by intravascular hemolysis which has been demonstrated to be
      effectively controlled with eculizumab. However, lactate dehydrogenase levels
      remain slightly elevated and haptoglobin levels remain low in some patients
      suggesting residual low-level hemolysis. This may be due to C3-mediated clearance
      of paroxysmal nocturnal hemoglobinuria red blood cells through the
      reticuloendothelial system. DESIGN AND METHODS: Thirty-nine samples from patients
      not treated with eculizumab and 31 samples from patients treated with eculizumab
      were obtained (for 17 of these 31 samples there were also samples taken prior to
      eculizumab treatment). Membrane bound complement was assessed by flow cytometry.
      Direct antiglobulin testing was carried out using two methods. Lactate
      dehydrogenase was assayed to assess the degree of hemolysis. RESULTS: Three of 39
      patients (8%) with paroxysmal nocturnal hemoglobinuria not on eculizumab had a
      positive direct antiglobulin test, while the test was positive in 21 of 31 (68%)
      during eculizumab treatment. Of these 21 patients who had a positive direct
      antiglobulin test during eculizumab treatment, 17 had been tested prior to
      treatment; only one was positive. Flow cytometry using anti-C3 monoclonal
      antibodies was performed on the 21 direct antiglobulin test-positive, eculizumab
      treated patients; the median proportion of C3-positive total red blood cells was
      26%. Among the eculizumab-treated patients, 16 of the 21 (76.2%) with a positive
      direct antiglobulin test received at least one transfusion compared with one of
      ten (10.0%) of those with a negative test (P<0.01). Among the eculizumab-treated
      patients, the mean hemoglobin value for the 21 with a positive direct
      antiglobulin test was 9.6+/-0.3 g/dL, whereas that in the ten patients with a
      negative test was 11.0+/-0.4 g/dL (P=0.02). CONCLUSIONS: These data demonstrate a
      previously masked mechanism of red cell clearance in paroxysmal nocturnal
      hemoglobinuria and suggests that blockade of complement at C5 allows C3 fragment
      accumulation on some paroxysmal nocturnal hemoglobinuria red cells, explaining
      the residual low-level hemolysis occurring in some eculizumab-treated patients.

PMID- 20145266
TI  - Thromboembolic events among adult patients with primary immune thrombocytopenia
      in the United Kingdom General Practice Research Database.
AB  - BACKGROUND: The risk of thromboembolic events in adults with primary immune
      thrombocytopenia has been little investigated despite findings of increased
      susceptibility in other thrombocytopenic autoimmune conditions. The objective of
      this study was to evaluate the risk of thromboembolic events among adult patients
      with and without primary immune thrombocytopenia in the UK General Practice
      Research Database. DESIGN AND METHODS: Using the General Practice Research
      Database, 1,070 adults (>or=18 years) with coded records for primary immune
      thrombocytopenia first referenced between January 1(st) 1992 and November 30(th)
      2007, and having at least one year pre-diagnosis and three months post-diagnosis
      medical history were matched (1:4 ratio) with 4,280 primary immune
      thrombocytopenia disease free patients by age, gender, primary care practice, and
      pre-diagnosis observation time. The baseline prevalence and incidence rate of
      thromboembolic events were quantified, with comparative risk modelled by Cox's
      proportional hazards regression. RESULTS: Over a median 47.6 months of follow-up
      (range: 3.0-192.5 months), adjusted hazard ratios of 1.58 (95% CI, 1.01-2.48),
      1.37 (95% CI, 0.94-2.00), and 1.41 (95% CI, 1.04-1.91) were found for venous,
      arterial, and combined (arterial and venous) thromboembolic events, respectively,
      when comparing the primary immune thrombocytopenia cohort with the primary immune
      thrombocytopenia disease free cohort. Further event categorization revealed an
      elevated incidence rate for each occurring venous thromboembolic subtype among
      the adult patients with primary immune thrombocytopenia. CONCLUSIONS: Patients
      with primary immune thrombocytopenia are at increased risk for venous
      thromboembolic events compared with patients without primary immune
      thrombocytopenia.

PMID- 20145267
TI  - Hematopoietic stem cells in co-culture with mesenchymal stromal cells--modeling
      the niche compartments in vitro.
AB  - BACKGROUND: Hematopoietic stem cells located in the bone marrow interact with a
      specific microenvironment referred to as the stem cell niche. Data derived from
      ex vivo co-culture systems using mesenchymal stromal cells as a feeder cell layer
      suggest that cell-to-cell contact has a significant impact on the expansion,
      migratory potential and 'stemness' of hematopoietic stem cells. Here we
      investigated in detail the spatial relationship between hematopoietic stem cells
      and mesenchymal stromal cells during ex vivo expansion. DESIGN AND METHODS: In
      the co-culture system, we defined three distinct localizations of hematopoietic
      stem cells relative to the mesenchymal stromal cell layer: (i) those in
      supernatant (non-adherent cells); (ii) those adhering to the surface of
      mesenchymal stromal cells (phase-bright cells) and (iii) those beneath the
      mesenchymal stromal cells (phase-dim cells). Cell cycle, proliferation, cell
      division and immunophenotype of these three cell fractions were evaluated from
      day 1 to 7. RESULTS: Phase-bright cells contained the highest proportion of
      cycling progenitors during co-culture. In contrast, phase-dim cells divided much
      more slowly and retained a more immature phenotype compared to the other cell
      fractions. The phase-dim compartment was soon enriched for CD34(+)/CD38(-) cells.
      Migration beneath the mesenchymal stromal cell layer could be hampered by
      inhibiting integrin beta1 or CXCR4. CONCLUSIONS: Our data suggest that the
      mesenchymal stromal cell surface is the predominant site of proliferation of
      hematopoietic stem cells, whereas the compartment beneath the mesenchymal stromal
      cell layer seems to mimic the stem cell niche for more immature cells. The SDF
      1/CXCR4 interaction and integrin-mediated cell adhesion play important roles in
      the distribution of hematopoietic stem cells in the co-culture system.

PMID- 20145268
TI  - Reconstitution of natural killer cell receptors influences natural killer
      activity and relapse rate after haploidentical transplantation of T- and B-cell
      depleted grafts in children.
AB  - BACKGROUND: Natural killer cells have been demonstrated to exert remarkable graft
      versus-leukemia effects after haploidentical transplantation. Acquisition of
      both, inhibiting and activating, receptors on developing natural killer cells is
      an important step in their functional maturation. Here, we report on the
      reconstitution of natural killer receptors after haploidentical transplantation
      of T-and B-cell (CD3/CD19) depleted grafts with co-transfusion of natural killer
      cells in children and its influence on natural killer cell activity and clinical
      outcome. DESIGN AND METHODS: We analyzed reconstitution patterns of natural
      killer receptors at different time intervals after haploidentical transplantation
      by multi-color flow cytometry. Natural killer cell activity and antibody
      dependent cellular cytotoxicity was tested against cell lines and leukemic blasts
      in vitro. Survival was analyzed using Kaplan-Meier estimates. RESULTS: Recovery
      of CD56(+)/CD16(+) cells was fast with high cytolytic activity against K562 and
      strong antibody-dependent cellular cytotoxicity activity against neuroblastoma
      and leukemic blasts as early as day 14 posttransplant. KIR reconstitution showed
      a predominance of KIR negative natural killer cells early after transplantation
      and an early reconstitution of CD158b compared to CD158a and CD158e. These
      differences were independent of presence or absence of the corresponding KIR
      ligands in donors or recipients. This reconstitution pattern was associated with
      a higher relapse probability of patients homozygous for HLA-C1-alleles compared
      to patients homozygous or even heterozygous for HLA-C2-alleles. CONCLUSIONS: Our
      results indicate a fast recovery of functional and alloreactive natural killer
      cells with a constant KIR pattern after haploidentical transplantation with T-
      and B-cell depleted grafts. Moreover, these natural killer cells can mediate
      antibody-dependent cellular cytotoxicity and therefore may allow for an early use
      of antibodies against residual malignant cells.

PMID- 20145269
TI  - Impact of the type of the BCR-ABL fusion transcript on the molecular response in
      pediatric patients with chronic myeloid leukemia.

PMID- 20145270
TI  - The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces
      apoptosis, down-regulates the CXCR4 chemokine receptor and impairs migration of
      chronic lymphocytic leukemia cells.
AB  - BACKGROUND: Chronic lymphocytic leukemia is a neoplastic disorder that arises
      largely as a result of defective apoptosis leading to chemoresistance. Stromal
      cell-derived factor-1 and its receptor, CXCR4, have been shown to play an
      important role in chronic lymphocytic leukemia cell trafficking and survival.
      DESIGN AND METHODS: Since histone acetylation is involved in the modulation of
      gene expression, we evaluated the effects of suberoylanilide hydroxamic acid, a
      histone deacetylase inhibitor, on chronic lymphocytic leukemia cells and in
      particular on cell survival, CXCR4 expression, migration, and drug sensitization.
      RESULTS: Here, we showed that treatment with suberoylanilide hydroxamic acid (20
      microM) for 48 hours induced a decrease in chronic lymphocytic leukemia cell
      viability via apoptosis (n=20, P=0.0032). Using specific caspase inhibitors, we
      demonstrated the participation of caspases-3, -6 and -8, suggesting an activation
      of the extrinsic pathway. Additionally, suberoylanilide hydroxamic acid
      significantly decreased CXCR4 mRNA (n=10, P=0.0010) and protein expression (n=40,
      P<0.0001). As a result, chronic lymphocytic leukemia cell migration in response
      to stromal cell-derived factor-1 (n=23, P<0.0001) or through bone marrow stromal
      cells was dramatically impaired. Consequently, suberoylanilide hydroxamic acid
      reduced the protective effect of the microenvironment and thus sensitized chronic
      lymphocytic leukemia cells to chemotherapy such as fludarabine. CONCLUSIONS: In
      conclusion, suberoylanilide hydroxamic acid induces apoptosis in chronic
      lymphocytic leukemia cells via the extrinsic pathway and down-regulates CXCR4
      expression leading to decreased cell migration. Suberoylanilide hydroxamic acid
      in combination with other drugs represents a promising therapeutic approach to
      inhibiting migration, chronic lymphocytic leukemia cell survival and potentially
      overcoming drug resistance.

PMID- 20145271
TI  - Low levels of monoclonal small B cells in the bone marrow of patients with
      diffuse large B-cell lymphoma of activated B-cell type but not of germinal center
      B-cell type.
AB  - BACKGROUND: Multiparameter flow cytometry allows the detection of minor
      monoclonal B-cell populations. Using this technique combined with morphology, we
      were struck by the presence of minor populations of small monoclonal B cells in
      bone marrows of patients with diffuse large B-cell lymphoma in routine diagnostic
      samples and performed a systematic retrospective study. DESIGN AND METHODS: Bone
      marrows of 165 patients with primary diffuse large B-cell lymphoma without
      histological evidence of concurrent non-Hodgkin's lymphoma were studied by
      routine microscopy of trephines and smears, immunohistochemistry and
      multiparameter flow cytometry. RESULTS: Diffuse large B-cell lymphoma
      infiltration in marrows was documented in 11 of 165 patients. Morphological
      examination consistently revealed a higher tumor load than evidenced by flow
      cytometry. Of interest, only 3 of 119 patients with diffuse large B-cell lymphoma
      not otherwise specified, the largest subtype, showed marrow infiltration. By
      contrast, flow cytometry revealed a minor monoclonal B-cell population in 24 of
      165 patients, none of whom showed diffuse large B-cell lymphoma infiltration by
      morphology. Of interest, morphological examination revealed the presence of small
      B cells in the marrows of those patients. Moreover, 11 of 39 (28.2%) of patients
      with diffuse large B-cell lymphoma not otherwise specified of ABC subtype and
      only 3 of 80 (3.7%) with the GCB subtype showed these monoclonal small B cells
      (P=0.0002). In addition 4 of 8 (50%), 4 of 15 (26.7%) and 2 of 3 (66.7%) patients
      with primary testicular, primary central nervous system and leg-type diffuse
      large B-cell lymphoma, respectively, showed monoclonal small B cells.
      CONCLUSIONS: Bone marrow infiltration with diffuse large B-cell lymphoma in
      patients with diffuse large B-cell lymphoma not otherwise specified is rare at
      diagnosis. By contrast, a high number of diffuse large B-cell lymphoma not
      otherwise specified of the ABC subtype but not of GCB subtype is associated with
      monoclonal small B cells in the marrow. Whether these monoclonal small B cells
      are precursors of diffuse large B-cell lymphoma of the ABC type or arise in a
      common background that favors clonal B-cell expansion remains to be demonstrated.

PMID- 20145272
TI  - The Southern French registry of genetic hemochromatosis: a tool for determining
      clinical prevalence of the disorder and genotype penetrance.
AB  - BACKGROUND: Despite great progress in understanding the mechanisms underlying
      genetic hemochromatosis, data on the prevalence and the penetrance of the
      disorder are conflicting. DESIGN AND METHODS: A registry of patients with genetic
      hemochromatosis was established in the South of France and a regional health
      network was developed to allow the inclusion of all the diagnosed patients. C282Y
      homozygous patients classified in stages 2 (biological iron overload), 3 and 4
      (clinical manifestations of iron overload, stage 4 being the more severe)
      according to the classification of the French National Authority for Health were
      included in the registry over a 6-year period. RESULTS: A total of 352
      symptomatic C282Y homozygotes were identified, resulting in a total prevalence of
      1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per
      10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among
      Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1%
      in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males
      (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of
      age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in
      subjects between 50 and 54 years old. Among 249 patients with complete records,
      24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4.
      There was a higher proportion of males, and excessive alcohol intake was more
      prevalent in stage 4 than in stages 2 and 3 combined. CONCLUSIONS: A French
      Mediterranean regional hemochromatosis registry with strict inclusion criteria is
      a useful tool for characterizing the history of this disease, particularly for
      the most severely affected patients, as defined by the disease severity
      classification. The total prevalence of symptomatic C282Y homozygotes in the
      region was found to be low. However, clinical penetrance (stages 3 and 4) was not
      negligible.

PMID- 20145273
TI  - High-dose imatinib improves cytogenetic and molecular remissions in patients with
      pretreated Philadelphia-positive, BCR-ABL-positive chronic phase chronic myeloid
      leukemia: first results from the randomized CELSG phase III CML 11 "ISTAHIT"
      study.
AB  - BACKGROUND: Imatinib 400 mg/day is the standard treatment for patients with
      chronic phase chronic myeloid leukemia. Recent reports suggested higher and more
      rapid cytogenetic and molecular responses with higher doses of imatinib. DESIGN
      AND METHODS: In this prospective international, multicenter phase III study, 227
      patients with pre-treated Philadelphia chromosome-positive, BCR-ABL-positive
      chronic myeloid leukemia were randomized to a standard-dose imatinib arm (400
      mg/day) or a high-dose imatinib arm (800 mg/day for 6 months followed by 400
      mg/day as maintenance therapy). In this planned interim analysis hematologic,
      cytogenetic and molecular responses as well as toxicity were evaluated. RESULTS:
      Compared to the standard-dose, high-dose imatinib led to higher rates of major
      and complete cytogenetic responses at both 3 months (major: 21% versus 37%,
      P=0.01; complete: 6% versus 25%, P<0.001) and 6 months (major: 34% versus 54%,
      P=0.009; complete: 20% versus 44%, P<0.001). This was paralleled by a
      significantly higher major molecular response rate at 6 months in the high-dose
      imatinib arm (11.8% versus 30.4%; P=0.003). At 12 months, the rates of major
      cytogenetic response (the primary end-point) were comparable between the two arms
      (57% versus 59%). In contrast to non-hematologic toxicities, grade 3/4
      hematologic toxicities were more common in the high-dose arm. Cumulative complete
      cytogenetic response rates were higher in patients without dose reduction in the
      high-dose arm (61%) than in the patients with no dose reduction in the standard
      dose arm (36%) (P=0.014). CONCLUSIONS: This is the first randomized phase III
      trial in patients with pre-treated chronic phase chronic myeloid leukemia
      demonstrating improvements in major cytogenetic response, complete cytogenetic
      response and major molecular response rates with high-dose imatinib therapy
      (ClinicalTrials.gov Identifier: NCT00327262).

PMID- 20145274
TI  - PIM serine/threonine kinases in the pathogenesis and therapy of hematologic
      malignancies and solid cancers.
AB  - The identification as cooperating targets of Proviral Integrations of Moloney
      virus in murine lymphomas suggested early on that PIM serine/threonine kinases
      play an important role in cancer biology. Whereas elevated levels of PIM1 and
      PIM2 were mostly found in hematologic malignancies and prostate cancer, increased
      PIM3 expression was observed in different solid tumors. PIM kinases are
      constitutively active and their activity supports in vitro and in vivo tumor cell
      growth and survival through modification of an increasing number of common as
      well as isoform-specific substrates including several cell cycle regulators and
      apoptosis mediators. PIM1 but not PIM2 seems also to mediate homing and migration
      of normal and malignant hematopoietic cells by regulating chemokine receptor
      surface expression. Knockdown experiments by RNA interference or dominant
      negative acting mutants suggested that PIM kinases are important for maintenance
      of a transformed phenotype and therefore potential therapeutic targets.
      Determination of the protein structure facilitated identification of an
      increasing number of potent small molecule PIM kinase inhibitors with in vitro
      and in vivo anticancer activity. Ongoing efforts aim to identify isoform-specific
      PIM inhibitors that would not only help to dissect the kinase function but
      hopefully also provide targeted therapeutics. Here, we summarize the current
      knowledge about the role of PIM serine/threonine kinases for the pathogenesis and
      therapy of hematologic malignancies and solid cancers, and we highlight
      structural principles and recent progress on small molecule PIM kinase inhibitors
      that are on their way into first clinical trials.

PMID- 20145275
TI  - Prognosis of children with mixed phenotype acute leukemia treated on the basis of
      consistent immunophenotypic criteria.
AB  - BACKGROUND: Mixed phenotype acute leukemia (MPAL) represents a diagnostic and
      therapeutic dilemma. The European Group for the Immunological Classification of
      Leukemias (EGIL) scoring system unambiguously defines MPAL expressing aberrant
      lineage markers. Discussions surrounding it have focused on scoring details, and
      information is limited regarding its biological, clinical and prognostic
      significance. The recent World Health Organization classification is simpler and
      could replace the EGIL scoring system after transformation into unambiguous
      guidelines. DESIGN AND METHODS: Simple immunophenotypic criteria were used to
      classify all cases of childhood acute leukemia in order to provide therapy
      directed against acute lymphoblastic leukemia or acute myeloid leukemia.
      Prognosis, genotype and immunoglobulin/T-cell receptor gene rearrangement status
      were analyzed. RESULTS: The incidences of MPAL were 28/582 and 4/107 for children
      treated with acute lymphoblastic leukemia and acute myeloid leukemia regimens,
      respectively. In immunophenotypic principal component analysis, MPAL treated as T
      cell acute lymphoblastic leukemia clustered between cases of non-mixed T-cell
      acute lymphoblastic leukemia and acute myeloid leukemia, while other MPAL cases
      were included in the respective non-mixed B-cell progenitor acute lymphoblastic
      leukemia or acute myeloid leukemia clusters. Analogously, immunoglobulin/T-cell
      receptor gene rearrangements followed the expected pattern in patients treated as
      having acute myeloid leukemia (non-rearranged, 4/4) or as having B-cell
      progenitor acute lymphoblastic leukemia (rearranged, 20/20), but were missing in
      3/5 analyzed cases of MPAL treated as having T-cell acute lymphobastic leukemia.
      In patients who received acute lymphoblastic leukemia treatment, the 5-year event
      free survival of the MPAL cases was worse than that of the non-mixed cases (53+/
      10% and 76+/-2% at 5 years, respectively, P=0.0075), with a more pronounced
      difference among B lineage cases. The small numbers of MPAL cases treated as T
      cell acute lymphoblastic leukemia or as acute myeloid leukemia hampered separate
      statistics. We compared prognosis of all subsets with the prognosis of previously
      published cohorts. CONCLUSIONS: Simple immunophenotypic criteria are useful for
      therapy decisions in MPAL. In B lineage leukemia, MPAL confers poorer prognosis.
      However, our data do not justify a preferential use of current acute myeloid
      leukemia-based therapy in MPAL.

PMID- 20145277
TI  - Social influences on health: is serotonin a critical mediator?
AB  - The influence of social relationships on health has been well documented for many
      years, yet identifying the physiological mechanisms responsible for these effects
      has proved more challenging. This review assesses the potential role of the
      serotonin system in affecting sensitivity to the health-related effects of the
      social environment. Building on recent studies of genetic variation in the
      serotonin system, particularly focusing on a polymorphism (5-HTTLPR) in the
      serotonin transporter gene, we provide evidence that activity within the
      serotonin system is critically involved in setting sensitivity to social
      experiences. Furthermore, we highlight the effects of the 5-HTTLPR on sensitivity
      to both positive and negative social experiences. In a positive environment,
      individuals with the short allele, and particularly the short/short genotype,
      function better psychologically than those with the long/long genotype.
      Conversely, when exposed to adverse environments or in the absence of social
      support, individuals with the short allele are at high risk for a variety of
      negative health outcomes. This serotoninergic involvement in social sensitivity
      seems to occur in concert with other neurochemical systems, such as the opioid
      system, which will also be discussed. Although this differential sensitivity to
      social experiences is initially determined in the brain, it has physiological
      effects on downstream pathways that more directly affect disease mechanisms, such
      as the hypothalamic-pituitary-adrenal axis, which is a particular focus of this
      review. The serotonin system, as indexed by the 5-HTTLPR, is an important link
      between the social environment and health.

PMID- 20145278
TI  - Theories of depression and anxiety and cardiovascular outcomes in psychosomatic
      medicine and behavioral cardiology.

PMID- 20145276
TI  - Outcome after relapse of acute lymphoblastic leukemia in adult patients included
      in four consecutive risk-adapted trials by the PETHEMA Study Group.
AB  - BACKGROUND: About one half of adults with acute lymphoblastic leukemia are not
      cured of the disease and ultimately die. The objective of this study was to
      explore the factors influencing the outcome of adult patients with relapsed acute
      lymphoblastic leukemia. DESIGN AND METHODS: We analyzed the characteristics, the
      outcome and the prognostic factors for survival after first relapse in a series
      of 263 adult patients with acute lymphoblastic leukemia (excluding those with
      mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four
      consecutive risk-adapted PETHEMA trials. RESULTS: The median overall survival
      after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival
      of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line
      treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them
      remained disease free at 5 years. Factors predicting a good outcome after rescue
      therapy were age less than 30 years (2-year overall survival of 21% versus 10%
      for those over 30 years old; P<0.022) and a first remission lasting more than 2
      years (2-year overall survival of 36% versus 17% among those with a shorter first
      remission; P<0.001). Patients under 30 years old whose first complete remission
      lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%)
      and a 5-year disease-free survival of 53% (95% CI, 34%-72%). CONCLUSIONS: The
      prognosis of adult patients with acute lymphoblastic leukemia who relapse is
      poor. Those aged less than 30 years with a first complete remission lasting
      longer than 2 years have reasonable possibilities of becoming long-term survivors
      while patients over this age or those who relapse early cannot be successfully
      rescued using the therapies currently available.

PMID- 20145281
TI  - Epidemiology of ankle sprain at the United States Military Academy.
AB  - BACKGROUND: Ankle sprain is a common injury in athletic populations that results
      in significant time lost to injury. HYPOTHESIS: The incidence rates (IRs) of
      ankle ligament sprains are influenced by gender, height, weight, body mass index
      (BMI), physical conditioning, level of competition, type of sport, and athlete
      exposure to sport. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A
      longitudinal cohort study was performed to determine the effect of risk factors
      for ankle sprain at the United States Military Academy between 2005 and 2007.
      RESULTS: A total 614 cadets sustained new ankle sprains during 10 511 person
      years at risk, resulting in an overall IR of 58.4 per 1000 person-years. Women
      (96.4), compared with men (52.7), had a significantly increased rate ratio (IRR)
      for ankle sprain of 1.83 (95% confidence interval [CI], 1.52-2.20). Men with
      ankle sprains had higher mean height, weight, and BMI than uninjured men (P
      <.001). Men with ankle sprains had higher average scores in push-ups, sit-ups,
      and run time than uninjured men (P <.001). Ankle sprain occurred most commonly
      during athletics (64.1%). Ankle sprain IR did not significantly differ between
      intercollegiate and intramural athletic competition after controlling for athlete
      exposure (IRR, 1.05; 95% CI, 0.81-1.37). The ankle sprain IRR of female compared
      with male intercollegiate athletes was 0.93 (95% CI, 0.67-1.32) per 1000 person
      years and 1.04 (95% CI, 0.74-1.47) per 1000 athlete-exposures. The
      intercollegiate sports of men's rugby, women's cheerleading, and men's/women's
      basketball, soccer, and lacrosse had the highest ankle sprain IR. CONCLUSION:
      Higher mean height and weight in men, increased BMI in men, greater physical
      conditioning in men, and athlete exposure to selected sports were all risk
      factors for ankle sprain.

PMID- 20145283
TI  - Innovative Contribution to Family Nursing Award 2009: Anna Stefansdottir, RN,
      MSc; Anna Olafia Sigurthardottir, RN, MS; Elisabet Konrathsdottir, RN, MSc; and
      Eydis Kristin Sveinbjarnardottir, RN, MSN.

PMID- 20145282
TI  - Prospective trial of thoracic and spine surgeons' updating of their estimated
      case durations at the start of cases.
AB  - BACKGROUND: Surgeon estimates of case durations are important for operating room
      (OR) management decision making because many cases are rare combinations of
      procedures with few or no historical data. Thoracic and spine surgeons updated
      their scheduled OR times on the day of surgery just before the "time out" in the
      OR. METHODS: All elective (scheduled) general thoracic (n = 39) and spine surgery
      (n = 48) cases at 1 hospital were studied over 3-month and 1.5-month periods,
      respectively. RESULTS: Among cases with a change in predicted duration, most
      changes were made based on updates to the surgical or anesthetic procedures
      (thoracic 85%, spine 86%). For thoracic surgery, there was overall no significant
      median reduction in absolute prediction error (median 0 minutes, 95% confidence
      interval [CI] 0-0 minutes). Among the 37% of cases with changed predicted
      durations, there was a significant reduction in absolute error (median 38
      minutes, 95% CI >7.5 minutes). For spine surgery, there was overall no reduction
      in the absolute error (median 0 minutes, 95% CI 0-0 minutes). Among the 29% of
      cases with changed predicted durations, absolute error was no worse, but not
      significantly better (point estimate of median reduction 34 minutes, 95% CI >0
      minutes). Secondary observations made were no effect of updates on bias, frequent
      rounding of scheduled durations to the nearest half hour, and increased
      predictive error caused by decisions that reduced expected overutilized OR time.
      CONCLUSIONS: A systematic program of routinely and/or always asking for updated
      case duration predictions will not substantively improve OR management decision
      making. However, when a change in surgical approach, surgical procedure, or
      anesthetic procedure is identified (e.g., at the intraoperative briefing before
      case start), the updated estimate of case duration should be used, because such
      updates are not worse and often better than original estimates.

PMID- 20145284
TI  - Implementing family nursing: how do we translate knowledge into clinical
      practice? Part II: The evolution of 20 years of teaching, research, and practice
      to a Center of Excellence in Family Nursing.
AB  - The author's reflections on knowledge transfer/translation highlight the
      importance of the circular process between science and practice knowledge,
      leading to the notion of "knowledge exchange." She addresses the dilemmas of
      translating knowledge into clinical practice by describing her academic
      contributions to knowledge exchange within Family Systems Nursing (FSN). Teaching
      and research strategies are offered that address the circularity between science
      and practice knowledge. The evolution of 20 years of teaching, research, and
      clinical experience has resulted in the recent creation of a Center of Excellence
      in Family Nursing at the University of Montreal. The three main objectives of the
      Center uniquely focus on knowledge exchange by providing (a) a training context
      for skill development for nurses specializing in FSN, (b) a research milieu for
      knowledge "creation" and knowledge "in action" studies to further advance the
      practice of FSN, and (c) a family healing setting to support families who
      experience difficulty coping with health issues.

PMID- 20145285
TI  - Family nursing research for practice: the Swedish perspective.
AB  - This article offers a synthesis of the significant developments and progress of
      family nursing in Sweden. A review was conducted to locate Swedish family nursing
      research produced over the past 10 years. CINAHL, Medline, and PubMed were the
      primary databases used to locate approximately 75 family nursing studies
      conducted in Sweden. The majority of the studies used descriptive methods with
      data collected from surveys and interviews involving nurses and family members
      either together or individually. Only a few of the studies examined family
      nursing interventions. This article also reports the results of a recent survey
      of Swedish nurses that examined how family nursing is used in practice. After 10
      years of creating a strong foundation for family-focused nursing in Sweden, there
      is still a need for nurse researchers, educators, and administrators to
      collaborate in the implementation of family nursing to practice.

PMID- 20145286
TI  - Research on caregiving in Chinese families living with mental illness: a critical
      review.
AB  - Much of the existing research on caregiving in families of individuals with
      mental illness has been conducted in Western societies. Therefore, the purpose of
      this review was to critically examine research on caregiving in families of
      individuals with mental illness living in Taiwan, Hong Kong, and Mainland China.
      A search using computerized databases, public search engines, and references from
      retrieved articles revealed 37 studies published from 1990 to 2009. Four studies
      were theory driven at an individual level, and one study was guided by a family
      level framework. Thirty-two articles were quantitative studies, and 5 were
      qualitative studies. All but 5 of 37 studies were cross-sectional. Findings
      suggest that misconceptions about mental illness, behavior disturbances,
      inadequate social support, and the limited value placed on caregiving contribute
      to maladaptation. Future research should include longitudinal studies guided by
      culturally appropriate family frameworks and studies using mixed methods.

PMID- 20145287
TI  - Being closely connected to health care providers experiencing burnout: putting
      one's life on hold to help.
AB  - Being closely connected to a person experiencing illness may be a trying
      experience.This study aimed to illuminate meanings of being closely connected to
      health care providers experiencing burnout. Ten interviews were conducted with
      five people closely connected (i.e., family members or supportive friends) to
      health care providers recovering from burnout. The interviews were tape-recorded
      and transcribed verbatim, and the resulting text was interpreted using a
      phenomenological-hermeneutic method. One consequence of being closely connected
      to health care providers experiencing burnout is putting one's life on hold to
      help. In facing an almost unmanageable burden, those closely connected revealed
      their own suffering, emphasizing their need for support. Health care
      professionals need to be aware that those who are closely connected to a person
      experiencing burnout may lack knowledge about burnout and its related challenges.
      It is to be hoped such knowledge would allow significant others to better support
      the person experiencing burnout and promote their own health.

PMID- 20145288
TI  - Launching a Center of Excellence in Family Nursing, University of Montreal,
      Montreal, Quebec, Canada H3C 3J7. fabie.duhamel@umontreal.ca.

PMID- 20145289
TI  - National council on family relations: update on the family health section.

PMID- 20145290
TI  - Association of apolipoproteins e4 and c1 with onset age and memory: a study of
      sporadic Alzheimer disease in Taiwan.
AB  - OBJECTIVE: To identify clinical manifestations and neuropsychological effects of
      Alzheimer disease (AD) in apolipoprotein (ApoE) e4 carriers and to investigate
      the relationships between ApoE HhaI polymorphism and apolipoprotein C1 (APOC1)
      HpaI polymorphism in Taiwanese patients with AD. PARTICIPANTS AND METHODS: A
      total of 127 patients with AD and 191 elderly individuals were screened for ApoE
      and APOC1 polymorphism. All patients underwent neuropsychological testing,
      including a Mini-Mental Status Examination (MMSE), Clinical Dementia Rating
      (CDR), and/or the Visual Association Memory Test (VAMT) with Cognitive Abilities
      Screening Instrument. RESULTS: The frequencies of the e4 and A alleles were
      significantly higher in the AD group. In the patients with AD, the e4 and A
      allele effects on those with an age-of-onset of 60 to 79 years were stronger than
      those with an age-of-onset of 80 years or higher. Visual Association Memory Test
      performance was significantly worse in e4-allele carriers but not in A-allele
      carriers, in the early AD, particularly in those affected with AD for less than 2
      years. Although there was no statistically significant difference in genotypic
      frequency between patients and controls, the 2 genes were linked. In addition,
      the presence of the AA genotype concomitant with the e4 allele may be better
      associated with AD diagnosis than either factor alone. CONCLUSION: We conclude
      that the e4 allele affects neuropsychological performance and illness morbidity.
      Concomitantly, ApoE e4 and APOC1 A alleles have a better association with AD than
      ApoE e4 alone. In addition, APOC1 may partially contribute to the pathogenesis of
      AD, but the nature of its relationship with e4 requires further investigation.

PMID- 20145291
TI  - Theoretical variance analysis of single- and dual-energy computed tomography
      methods for calculating proton stopping power ratios of biological tissues.
AB  - We discovered an empirical relationship between the logarithm of mean excitation
      energy (ln Im) and the effective atomic number (EAN) of human tissues, which
      allows for computing patient-specific proton stopping power ratios (SPRs) using
      dual-energy CT (DECT) imaging. The accuracy of the DECT method was evaluated for
      'standard' human tissues as well as their variance. The DECT method was compared
      to the existing standard clinical practice-a procedure introduced by Schneider et
      al at the Paul Scherrer Institute (the stoichiometric calibration method). In
      this simulation study, SPRs were derived from calculated CT numbers of known
      material compositions, rather than from measurement. For standard human tissues,
      both methods achieved good accuracy with the root-mean-square (RMS) error well
      below 1%. For human tissues with small perturbations from standard human tissue
      compositions, the DECT method was shown to be less sensitive than the
      stoichiometric calibration method. The RMS error remained below 1% for most cases
      using the DECT method, which implies that the DECT method might be more suitable
      for measuring patient-specific tissue compositions to improve the accuracy of
      treatment planning for charged particle therapy. In this study, the effects of CT
      imaging artifacts due to the beam hardening effect, scatter, noise, patient
      movement, etc were not analyzed. The true potential of the DECT method achieved
      in theoretical conditions may not be fully achievable in clinical settings.
      Further research and development may be needed to take advantage of the DECT
      method to characterize individual human tissues.

PMID- 20145292
TI  - The reduction of image noise and streak artifact in the thoracic inlet during low
      dose and ultra-low dose thoracic CT.
AB  - Increased pixel noise and streak artifact reduce CT image quality and limit the
      potential for radiation dose reduction during CT of the thoracic inlet. We
      propose to quantify the pixel noise of mediastinal structures in the thoracic
      inlet, during low-dose (LDCT) and ultralow-dose (uLDCT) thoracic CT, and assess
      the utility of new software (quantum denoising system and BOOST3D) in addressing
      these limitations. Twelve patients had LDCT (120 kV, 25 mAs) and uLDCT (120 kV,
      10 mAs) images reconstructed initially using standard mediastinal and lung
      filters followed by the quantum denoising system (QDS) to reduce pixel noise and
      BOOST3D (B3D) software to correct photon starvation noise as follows: group 1 no
      QDS, no B3D; group 2 B3D alone; group 3 QDS alone and group 4 both QDS and B3D.
      Nine regions of interest (ROIs) were replicated on mediastinal anatomy in the
      thoracic inlet, for each patient resulting in 3456 data points to calculate pixel
      noise and attenuation. QDS reduced pixel noise by 18.4% (lung images) and 15.8%
      (mediastinal images) at 25 mAs. B3D reduced pixel noise by approximately 8% in
      the posterior thorax and in combination there was a 35.5% reduction in effective
      radiation dose (E) for LDCT (1.63-1.05 mSv) in lung images and 32.2% (1.55-1.05
      mSv) in mediastinal images. The same combination produced 20.7% reduction (0.53
      0.42 mSv) in E for uLDCT, for lung images and 17.3% (0.51-0.42) for mediastinal
      images. This quantitative analysis of image quality confirms the utility of
      dedicated processing software in targeting image noise and streak artifact in
      thoracic LDCT and uLDCT images taken in the thoracic inlet. This processing
      software potentiates substantial reductions in radiation dose during thoracic
      LDCT and uLDCT.

PMID- 20145293
TI  - MRI-guided robotic system for transperineal prostate interventions: proof of
      principle.
AB  - In this study, we demonstrate the proof of principle of the University Medical
      Center Utrecht (UMCU) robot dedicated to magnetic resonance imaging (MRI)-guided
      interventions in patients. The UMCU robot consists of polymers and non
      ferromagnetic materials. For transperineal prostate interventions, it can be
      placed between the patient's legs inside a closed bore 1.5T MR scanner. The robot
      can manually be translated and rotated resulting in five degrees of freedom. It
      contains a pneumatically driven tapping device to automatically insert a needle
      stepwise into the prostate using a controller unit outside the scanning room. To
      define the target positions and to verify the needle insertion point and the
      needle trajectory, a high-resolution 3D balanced steady state free precession
      (bSSFP) scan that provides a T2/T1-weighted contrast is acquired. During the
      needle insertion fast 2D bSSFP images are generated to track the needle on-line.
      When the target position is reached, the radiation oncologist manually places a
      fiducial gold marker (small seed) at this location. In total two needle
      trajectories are used to place all markers. Afterwards, a high-resolution 3D
      bSSFP scan is acquired to visualize the fiducial gold markers. Four fiducial gold
      markers were placed transperineally into the prostate of a patient with a
      clinical stage T3 prostate cancer. In the generated scans, it was possible to
      discriminate the patient's anatomy, the needle and the markers. All markers were
      delivered inside the prostate. The procedure time was 1.5 h. This study proves
      that MRI-guided needle placement and seed delivery in the prostate with the UMCU
      robot are feasible.

PMID- 20145294
TI  - Possible ancient origin of heterochromatic JNK sequences in chromosomes 2R of
      Secale vavilovii Grossh.
AB  - Employing FISH analysis as well as BLAST and CUSTAL W (1.82) programs, we
      investigated types of DNA nucleotide sequences building an additional
      heterochromatic band in 2R chromosomes of 3 lines of Secale vavilovii Grossh. The
      probes used in FISH analysis were designed based on the reverse transcriptase
      sequence of Ty1-copia and Ty3-gypsy retrotransposons and the 5S rRNA gene
      sequence. No hybridization signals from the reverse transcriptase probes were
      observed in the chromosome region where the additional band occurs. On the other
      hand, signals were observed after hybridization with the 5S rDNA probe, clearly
      suggesting the presence of that type of sequences in the analyzed heterochromatin
      band. Using BLAST and CUSTAL W programs, we revealed high similarity of the JNK1
      sequence to the 5S rRNA gene from Hordeum chilense (HCH1016, HCH1018, 88%) and to
      a fragment of the 5S rRNA sequence of H. marinum (HMAR003, 97%). In addition, the
      same fragment of JNK1 was shown to be very similar to the part of the Angela
      retrotransposon (92%) as well as to the SNAC 426K20-1 transposon (89%) belonging
      to CACTA family, both from Triticum monococcum, and to Zingeria biebersteiniana
      pericentromeric sequences (78%). The similarity of JNK1 to those sequences may be
      accidental or the JNK1 may represent an ancient mobile genetic element that
      caught the 5S rRNA sequence. During the evolution those sequences might have been
      accumulated in the particular region on the 2R chromosome. Our results suggest
      that the additional heterochromatin band in chromosomes 2R of S. vavilovii is a
      collection of defective genes and/or mobile genetic elements.

PMID- 20145295
TI  - Molecular characterization of novel low-molecular-weight glutenin genes in
      Aegilops longissima.
AB  - Extensive genetic variations of low-molecular-weight glutenin subunits (LMW-GS)
      and their coding genes were found in the wild diploid A- and D-genome donors of
      common wheat. In this study, we reported the isolation and characterization of 8
      novel LMW-GS genes from Ae.longissima Schweinf. & Muschl., a species of the
      section Sitopsis of the genus Aegilops, which is closely related to the B genome
      of common wheat. Based on the N-terminal domain sequences, the 8 genes were
      divided into 3 groups. A consensus alignment of the extremely conserved domains
      with known gene groups and the subsequent cluster analysis showed that 2 out of
      the 3 groups of LMW-GS genes were closely related to those from the B genome, and
      the remaining was related to those from A and D genomes of wheat and Ae.
      tauschii. Using 3 sets of gene-group-specific primers, PCRs in diploid,
      tetraploid and hexaploid wheats and Ae. tauschii failed to obtain the expected
      products, indicating that the 3 groups of LMW-GS genes obtained in this study
      were new members of LMW-GS multi-gene families. These results suggested that the
      Sitopsis species of the genus Aegilops with novel gene variations could be used
      as valuable gene resources of LMW-GS. The 3 sets of group-specific primers could
      be utilized as molecular markers to investigate the introgression of novel alien
      LMW-GS genes from Ae. longissima into wheat.

PMID- 20145296
TI  - Saturation and mapping of a major Fusarium head blight resistance QTL on
      chromosome 3BS of Sumai 3 wheat.
AB  - Fusarium head blight (FHB) is a destructive disease in wheat. The major
      quantitative trait locus (QTL) on 3BS from Sumai 3 and its derivatives has been
      used as a major source of the resistance to FHB worldwide, but the discrepancy in
      reported location of the major QTL could block its using in map based cloning and
      marker assisted selection. In this study, Chinese Spring-Sumai 3 chromosome 3B
      substitution line was used as resistant parent of the mapping population to
      reduce the confounded effect of genetic background in Sumai 3. The major QTL
      region was saturated with the Sequence Tagged Microsatellite (STM) and Sequence
      Tagged Site (STS) markers. A linkage map of chromosome 3B with 36 markers
      covering a genetic distance of 112.4 cM was constructed. Twelve new markers were
      inserted into the chromosome region where the major QTL was located. The average
      interval distance between markers was 1.5 cM. Multiple QTL Models (MQM) mapping
      indicated that the major QTL was located in the interval of Xgwm533-Xsts9-1, and
      explained 45.6% of phenotypic variation of the resistance to FHB. The SSR (simple
      sequence repeat) marker Xgwm533 and STM marker Xstm748tcac are closely linked to
      the major QTL.

PMID- 20145297
TI  - Random variability of map distances based on Kosambi's and Haldane's mapping
      functions.
AB  - The majority of published genetic maps are based on Kosambi distances or on
      Haldane distances. For a comparison of both map distance measures, their random
      variability is of particular interest. For the statistic 'variance', this paper
      presents a relationship between Kosambi distances and Haldane distances. The
      results suggest that Kosambi distances exhibit a smaller random variability. The
      theoretical results are applied to an experimental data set for molecular AFLP
      markers linked to the bolting gene of sugar beet (Beta vulgaris L.).

PMID- 20145298
TI  - Self-incompatibility alleles in Polish wild pear (Pyrus pyraster (L.) Burgsd.): a
      preliminary analysis.
AB  - Wild pear (Pyrus pyraster, syn. P. communis var. pyraster) is thought to be one
      of the species that gave rise to all other members of the genus Pyrus, although
      intraspecific hybridizations with cultivated varieties could cause the
      disappearance of original species characteristics. S-RNase alleles from 7
      different wild pear individuals, collected from various regions of Poland, were
      cloned on the basis of the PCR method and nucleotide sequence analyses. The
      hypervariable (HV) region is responsible for allele-specific S-RNase activity in
      the self-incompatibility mechanism. The high level of polymorphism of its
      sequences may constitute a source of valuable phylogenetic information. From all
      individuals, 14 sequences were obtained successfully, and 9 of them were novel
      alleles. Phylogenetic analysis of these alleles was based on the amino acid
      sequence interpretation of coding regions and intron nucleotide sequences. The
      research conducted on a limited pool of available P. pyraster alleles gives only
      an initial insight into possible S-RNase allele polymorphisms in wild
      populations. At this stage, the results do not confirm a strong influence of
      cultivated pear species on the wild pear.

PMID- 20145299
TI  - Transcriptomic signature of cell lines isolated from canine mammary
      adenocarcinoma metastases to lungs.
AB  - Metastasis is a final step in the progression of mammary gland cancer, usually
      leading to death. Potentially, a molecular signature of metastasis can be defined
      via comparison of primary tumors with their metastases. Currently, there is no
      data in the literature regarding the molecular portrait of metastases in dogs and
      only few reports regarding human cancer. This is the first report describing the
      transcriptomic signature of canine cancer metastatic cells. Two adenocarcinoma
      cell lines isolated from the canine mammary gland (CMT-W1 and CMT-W2) were
      compared with cell lines isolated from their lung metastases (CMT-W1M and CMT
      W2M) with regards to the following cytometric parameters: cell cycle, ploidy, Bcl
      2 expression, susceptibility to induced apoptosis, and transcriptomic profile.
      Cytometric analyses revealed significant differences in cell cycle and
      antiapoptotic potential between the examined cells. Using oligonucleotide
      microarrays, we found 104 up-regulated genes in the metastatic cell line CMT-W1M
      and 21 up-regulated genes in the primary CMT-W1 cell line. We also found 83 up
      regulated genes in the CMT-W2M cell line and only 21 up-regulated genes in the
      CMT-W2 cell line. Among the up-regulated genes in both metastatic cell lines, we
      found 15 common genes. These differently expressed genes are involved mainly in
      signal transduction, cell structure and motility, nucleic acid metabolism,
      developmental processing, and apoptosis (GHSR, RASSF1, ARF1GAP, WDR74, SMOC2,
      SFRP4, DIAPH1, FSCN1, ALX4, SNX15, PLD2, WNT7B, POU6F2, NKG7, and POLR2F). Seven
      of them are involved in a cellular pathway dependent on ghrelin via growth
      hormone secretagogue receptor (GHSR). Our results suggest that this pathway may
      be essential for mammary cancer cells to have a metastatic potential.

PMID- 20145300
TI  - Association of 3 polymorphisms in porcine troponin I genes (TNNI1 and TNNI2) with
      meat quality traits.
AB  - The contractile protein troponin I (TnI), a constituent protein of the troponin
      complex located on the thin filaments of striated muscle, is involved in
      inhibition of calcium-induced myosin ATPase activity (and thus contraction). TnI
      slow (slow-twitch skeletal muscle isoform, named TNNI1) and TnI-fast (fast-twitch
      skeletal muscle isoform, named TNNI2) are muscle-fiber-type-specific proteins,
      and expression of their genes may affect the composition of muscle fiber, thereby
      influencing the meat quality traits. Thus, the TnI genes are potential candidate
      genes for traits related to meat quality in animals. Association of 2 SNPs
      (EU743939:g.5174T>C in intron 4, and EU743939:g.8350C>A in intron 7) of the TNNI1
      gene and a SNP (EU696779:g.1167C>T in intron 3) of the TNNI2 gene with 11 meat
      quality traits were studied on 334 Large White x Meishan F(2) pigs. In the TNNI1
      gene, g.5174T>C and g.8350C>A were found to be significantly associated with
      intramuscular fat content and meat color value of biceps femoris. The g.5174T>C
      also showed significant effects on meat color value and marbling score of
      longissimus dorsi, as well as pH of longissimus dorsi and semispinalis capitis.
      The g.1167C>T polymorphism in the TNNI2 gene affected significantly the pH of
      longissimus dorsi, meat color value of longissimus dorsi and semispinalis
      capitis, marbling score of longissimus dorsi, and intramuscular fat.

PMID- 20145301
TI  - A novel single-nucleotide polymorphism of the visfatin gene and its associations
      with performance traits in the chicken.
AB  - Visfatin is a peptide that is predominantly expressed in visceral adipose tissue
      and is hypothesized to be related to obesity and insulin resistance. In this
      study, a novel silent single-nucleotide polymorphism (SNP) was found in exon 7 of
      the chicken visfatin gene (also known as PBEF1) by single-stranded conformation
      polymorphism (SSCP) and DNA sequencing. In total, 836 chickens forming an F2
      resource population of Gushi chicken crossed with Anka broiler were genotyped by
      XbaI forced RFLP, and the associations of this polymorphism with chicken growth,
      carcass characteristics, and meat quality were analyzed. Significant associations
      were found between the polymorphism and 4-week body weight (BW4), 6-week body
      weight (BW6), 4-week body slanting length (BSL4), fat bandwidth (FBW), breast
      muscle water loss rate (BWLR) and breast muscle fiber density (BFD) (P < 0.05),
      as well as 4-week breastbone length (BBL4) (P < 0.01). These observations
      suggested that the polymorphism in exon7 of the visfatin gene had significant
      effects on the early growth traits of chicken.

PMID- 20145302
TI  - Genetic differences between wild and hatchery populations of Diplodus sargus and
      D. vulgaris inferred from RAPD markers: implications for production and
      restocking programs design.
AB  - Restocking and stock enhancement programs are now recognized as an important tool
      for the management of fishery resources. It is important, however, to have an
      adequate knowledge on the genetic population structure of both the released stock
      and the wild population before carrying out such programs. In this study, random
      amplified polymorphic DNA (RAPD) markers were applied to assess genetic diversity
      and population structure of wild and hatchery populations of the white seabream
      Diplodus sargus and the common two-banded seabream D. vulgaris (Sparidae). The
      estimated values for intrapopulation genetic variation, measured using the
      percentage of polymorphic loci (%P), Shannon index (H'), and Nei's gene diversity
      (h), showed high values for all populations. The percentage of genetic variation
      within D. sargus and D. vulgaris populations, based on coefficient of gene
      differentiation, reached 82.5% and 90% of the total genetic variation,
      respectively. An undeniable decrease in genetic variation was found in both
      hatchery populations, particularly in D. sargus, compared to the wild ones.
      However, the high values of variation within all populations and the low levels
      of genetic variation among populations did not indicate inbreeding or depression
      effects, thus indicating a fairly proper hatchery management. Nevertheless, the
      results of this study highlight the importance of monitoring the genetic
      variation of hatchery populations, particularly those to be used in restocking
      programs. The creation of a genetic baseline database will contribute to a more
      efficient conservation management and to the design of genetically sustainable
      restocking programs.

PMID- 20145303
TI  - Cross-species amplification of microsatellite markers in the invasive spiny-cheek
      crayfish (Orconectes limosus): assessment and application.
AB  - The North American spiny-cheek crayfish, Orconectes limosus (Cambaridae),
      endangered in its native range, is a widespread invasive species in European
      waters and conservationally important carrier of crayfish plague. However, its
      population structure is poorly known, and no informative genetic markers for the
      species are available. We tested cross-species transfer of microsatellite loci to
      spiny-cheek crayfish from 5 other crayfish species. Variability of 10
      successfully amplifying loci derived from 4 species was then tested in 60
      individuals of O. limosus originating from 3 natural populations: the river
      Danube at Bogyiszlo in Hungary, a pond in Stary Klieov, and the brook Eernovicky,
      both in the Czech Republic. The allele number within the populations ranged from
      4 to 10 alleles per locus, while heterozygosity levels varied from 0.650 to 0.900
      for H(o) and from 0.660 to 0.890 for H(e). No linkage disequilibrium and no null
      alleles were detected. The selected markers are useful for assessing population
      structure, intraspecific variation, and paternity studies in spiny-cheek
      crayfish.

PMID- 20145304
TI  - DNA damage and repair after exposure to sevoflurane in vivo, evaluated in Swiss
      albino mice by the alkaline comet assay and micronucleus test.
AB  - The relationship between DNA damage and repair of peripheral blood leukocytes,
      liver, kidney and brain cells was investigated in Swiss albino mice (Mus musculus
      L.) after exposure to sevoflurane (2.4 vol% for 2 h daily, for 3 days). Genetic
      damage of mouse cells was investigated by the comet assay and micronucleus test.
      To perform the comet assay, mice were divided into a control group and 4 groups
      of exposed mice sacrificed on day 3 of the experiment, at 0, 2, 6 or 24 h after
      the last exposure to sevoflurane. Mean tail length (TL), tail moment (TM), and
      tail intensity (TI) values were significantly higher in exposed mice (all
      examined organs) than in the control group. Significant DNA damage immediately
      after exposure to sevoflurane was observed in leukocytes. Damage induction in the
      liver, kidney, and brain occurred 6 h later than in leukocytes, as expected
      according to the toxicokinetics of the drug, where blood is the first compartment
      to absorb sevoflurane. However, none of the tested tissues revealed signs of
      repair until 24 h after the exposure. To distinguish the unrepaired genome damage
      in vivo, the micronucleus test was applied. Number of micronuclei in
      reticulocytes showed a statistically significant increase, as compared with the
      control group at all observed times after the treatment.

PMID- 20145305
TI  - Association between alpha-adducin gene polymorphism (Gly460Trp) and genetic
      predisposition to salt sensitivity: a meta-analysis.
AB  - Linkage and association studies suggested the relationship between alpha-adducin
      polymorphism (Gly460Trp; rs4961) and genetic susceptibility to salt-sensitivity.
      However, the currently available results were inconsistent. This study aimed to
      define quantitatively the association between salt-sensitivity and alpha-adducin
      Gly460Trp polymorphism in all published case-control studies. Publications from
      PubMed and other databases were retrieved. The major inclusion criteria were: (1)
      case-control design; (2) salt-sensitivity confirmed by sodium loading tests, and
      (3) the distribution of genotypes given in detail. Seven case-control studies
      fulfilled the inclusion criteria. In total they involved 820 subjects (454 salt
      sensitive and 366 non-salt-sensitive). The meta-analysis shows that Gly460Trp
      polymorphism in general is not significantly associated with salt-sensitivity [OR
      (95%CI): 1.40 (0.96, 2.04), P = 0.08]. Subgroup analysis showed that the
      association is statistically significant in Asian people [OR (95%CI):1.33 (1.06,
      1.69), P = 0.02] but not in Caucasian people [OR (95%CI):1.98 (0.57, 6.92), P =
      0.28]. This indicates that blood pressure response to sodium varies between
      ethnical groups. More studies based on a larger population are required to
      evaluate further the role of alpha-adducin Gly460Trp polymorphism in salt
      sensitive hypertension.

PMID- 20145306
TI  - Molecular characterization of Polish patients with familial hypercholesterolemia:
      novel and recurrent LDLR mutations.
AB  - Autosomal dominant hypercholesterolemia (ADH) is caused by mutations in the genes
      coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B-100
      (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study,
      a molecular analysis of LDLR and APOB was performed in a group of 378 unrelated
      ADH patients, to explore the mutation spectrum that causes hypercholesterolemia
      in Poland. All patients were clinically diagnosed with ADH according to a uniform
      protocol and internationally accepted WHO criteria. Mutational analysis included
      all exons, exon-intron boundaries and the promoter sequence of the LDLR, and a
      fragment of exon 26 of APOB. Additionally, the MLPA technique was applied to
      detect rearrangements within LDLR. In total, 100 sequence variations were
      identified in 234 (62%) patients. Within LDLR, 40 novel and 59 previously
      described sequence variations were detected. Of the 99 LDLR sequence variations,
      71 may be pathogenic mutations. The most frequent LDLR alteration was a point
      mutation p.G592E detected in 38 (10%) patients, followed by duplication of exons
      4-8 found in 16 individuals (4.2%). Twenty-five cases (6.6%) demonstrated the
      p.R3527Q mutation of APOB. Our findings imply that major rearrangements of the
      LDLR gene as well as 2 point mutations (p.G592E in LDLR and p.R3527Q in APOB) are
      frequent causes of ADH in Poland. However, the heterogeneity of LDLR mutations
      detected in the studied group confirms the requirement for complex molecular
      studies of Polish ADH patients.

PMID- 20145308
TI  - Severe clinical course of Hirschsprung disease in a Mowat-Wilson syndrome
      patient.
AB  - We present a clinical case of a female infant with multiple anomalies and
      distinctive facial features, with an exceptionally severe clinical course of
      Hirschsprung disease. The girl was also diagnosed with Mowat-Wilson syndrome,
      confirmed by molecular analysis as a heterozygous deletion of the ZEB2 gene.
      Moreover, molecular karyotyping revealed a deletion involving further genes
      (KYNU, ARHGAP15, and GTDC1).

PMID- 20145307
TI  - Rhizomelic chondrodysplasia punctata type 1: report of mutations in 3 children
      from India.
AB  - Rhizomelic chondrodysplasia punctata is a rare autosomal recessive disorder
      characterized by stippled epiphyses and rhizomelic shortening of the long bones.
      We report 3 subjects of rhizomelic chondrodysplasia punctata from India and the
      PEX7 mutations identified in them. The common PEX7-L292X allele, whose high
      frequency is due to a founder effect in the northern European Caucasian
      population, was not identified in these patients. Instead, 2 novel alleles are
      described, including 64_65delGC, which was present on a single PEX7 haplotype and
      could represent a common allele in the Indian population.

PMID- 20145310
TI  - SERS measurements of magnetic stretching force-induced trans-gauche
      conformational change.
AB  - The effects of stretching forces on covalently bridged 3-mercaptopropanoic acid
      molecules between magnetic particles (MPs) and Ag nano-particles (NPs) were
      studied by surface-enhanced Raman scattering (SERS) spectroscopy. With an
      exertion of 100 pN per single MP, the intensity ratio of the C-S stretching
      vibrations for trans-to-gauche conformations was increased from 0.295 +/- 0.008
      to 0.69 +/- 0.09. From the experimental result, it was concluded that the
      magnetic forces increased the distance between the MP and the Ag NP surface, and
      induced a shift of the isomerization equilibrium to the trans conformation. The
      present approach is a new candidate for a dynamic force spectroscopy of
      conformational equilibria.

PMID- 20145311
TI  - Conducting polymer-coated electrode as a reference/counter electrode in an
      organic phase and its application to a two-electrode type thin-layer cell for
      voltammetry at the liquid | liquid interface.
AB  - An indium tin oxide glass electrode coated with poly(3,4-ethylenedioxythiophene),
      PEDOT, PEDOT-ITOE, was proposed as an electrode workable as both a reference
      electrode and a counter one, a reference/counter electrode, in an organic phase
      and applied to a thin-layer cell of a two-electrode system for voltammetry at the
      liquid | liquid interface. By oxidizing the PEDOT film by 50% and doping a
      supporting electrolyte anion in an organic phase into the PEDOT film, a suitable
      depolarization was realized at the PEDOT | organic phase interface. The partially
      oxidized PEDOT-ITOE showed a Nerntian response to the supporting electrolyte
      anion concentration in the organic phase. The electrode potential was stable
      within +/-3 mV for 12 h, and showed a consistent value among the PEDOT-ITOEs
      prepared under the same procedure (the error range was about 7 mV, n = 8).

PMID- 20145312
TI  - Fabrication of a carbon sphere-modified electrode and sensitive determination of
      cadmium(II).
AB  - A carbon sphere-modified glass carbon electrode was prepared by employing
      cyclohexanol as a solvent to disperse the carbon spheres efficiently. The
      resulting electrode exhibits excellent sensitivity to cadmium(II), and a
      detection limit of 10(-10) mol/L has been obtained, which is one order of
      magnitude lower than those obtained by other electrodes. Along with immunity from
      interference of other metal ions, the wide determination range and good linear
      correlation coefficient would be beneficial to applications of the electrode.

PMID- 20145314
TI  - Guest editorial. The concept of surface analysis.

PMID- 20145313
TI  - Simultaneous injection-effective mixing analysis of palladium.
AB  - A novel concept of simultaneous injection-effective mixing analysis (SIEMA) is
      proposed, and a SIEMA method applied to the spectrophotometric determination of
      palladium using a water-soluble chromogenic reagent has been demonstrated. The
      flow configuration of SIEMA is a hybrid format of flow injection analysis (FIA),
      sequential injection analysis (SIA) and multicommutation in flow-based analysis.
      Sample and reagent solutions are aspirated into each holding coil through each
      solenoid valve by a syringe pump, and then the zones are simultaneously dispensed
      (injected) into a mixing coil by reversed flow toward a detector through a
      confluence point. This results in effective mixing and rapid detection with low
      reagent consumption.

PMID- 20145315
TI  - Introductory photoemission theory.
AB  - An introductory review is presented on the basis of many-body scattering theory.
      Some fundamental aspects of photoemission theory are discussed in detail. A few
      applications are also discussed; photoelectron diffraction, depth distribution
      function and multi-atom resonant photoemission are also discussed briefly.

PMID- 20145316
TI  - Determination of surface composition by X-ray photoelectron spectroscopy taking
      into account elastic photoelectron collisions.
AB  - It is now well known that elastic photoelectron scattering in the surface region
      of solids cannot be ignored in the mathematical formalism of quantitative XPS.
      Elastic collisions may increase or decrease the photoelectron signal intensity,
      depending on the experimental configuration. Consequently, it is advisable to
      take into account these effects in calculations of the surface composition. In
      certain experimental geometries, the photoelectron intensity is practically
      unaffected by elastic scattering events (configurations defined by the so-called
      "Master Angle"), and in principle such geometries should be recommended for
      measurements. Unfortunately, they usually cannot be implemented in typical
      constructions of spectrometers. In the present paper, different procedures for
      estimating corrections for elastic scattering events are overviewed. The
      influence of these correction procedures has been illustrated on examples of
      AuAgCu and AuAgPdCu alloys. It turned out that elastic photoelectron collisions
      substantially decrease the signal intensities selected for analysis. However,
      they are diminished by roughly the same factor. As a consequence, the calculated
      surface composition is only slightly modified by the correction procedure. This
      effect may not be of general validity for all solids, and the algorithms for
      calculating the surface composition should have an option for including any
      elastic scattering effects. Further efforts are needed to improve the predictive
      formulas providing corrections for elastic scattering effects.

PMID- 20145317
TI  - Surface excitations in surface electron spectroscopies studied by reflection
      electron energy-loss spectroscopy and elastic peak electron spectroscopy.
AB  - Surface excitations, in addition to bulk excitation, undergone by signal
      electrons in surface electron spectroscopies, such as Auger electron
      spectroscopy, and X-ray photoelectron spectroscopy, play an important role in the
      formation of electron spectra. Those inelastic scattering processes not only
      induce decay in the peak intensity, but also form background appearing in the
      lower kinetic energy side of relevant peaks. Information on surface excitation is
      essential in addition to bulk excitations for the quantification of material
      surfaces by surface electron spectroscopies, and extensive studies have been
      devoted to it. In this report, we introduce the basics of the study of surface
      excitations by reflection electron energy loss spectroscopy (REELS) and elastic
      peak electron spectroscopy (EPES). The application of several approaches within
      the schemes of EPES analysis and REELS analysis to the experimental determination
      of inelastic scattering parameters, such as the surface excitation parameter
      (SEP), differential SEP (DSEP), inelastic mean free path (IMFP), and dielectric
      function, are also introduced. Information useful to calculate the values of the
      IMFP and SEP using predictive equations is provided in Supporting Information as
      well.

PMID- 20145318
TI  - Electron spectroscopy of corrugated solid surfaces.
AB  - This paper reviews work done of the influence of non-ideal surface topography on
      electron spectral intensities of surface-sensitive electron spectroscopic
      methods: primarily X-ray induced photoelectron spectroscopy (XPS) and concise
      Auger electron spectroscopy (AES), electron energy loss spectroscopy in the
      reflection mode (REELS), and elastic peak electron spectroscopy (EPES). Several
      attempts to solve the problem are mentioned, where (i) the effect of surface
      roughness is corrected using a single parameter, (ii) computer simulations based
      on a model of surface roughness composed of regular geometrical units are used
      for electron spectral intensity calculations, and finally, (iii) a semi-empirical
      method based on careful surface mapping of analyzed sample by atomic force
      microscopy (AFM) is discussed in greater detail. The first approach was found to
      be rather simple to properly include any complex surface topography. The second
      technique can help us to understand surface topography related phenomena. The
      latter method, suitable for arbitrary rough solid surfaces covered by conformal
      overlayer(s), can be incorporated in current quantitative procedures valid for
      ideally flat surfaces.

PMID- 20145319
TI  - Appearance potential spectroscopy (APS): old method, but applicable to study of
      nano-structures.
AB  - An old surface analytical method, appearance potential spectroscopy (APS), which
      can probe empty electronic states, is briefly reviewed, since it has an ability
      to be applied to studying nanostructures. Although the theoretical calculation of
      the APS spectra including a two-electron process is not much simpler than that of
      x-ray absorption spectroscopy (XAS) spectra with a one-electron process,
      measurements of the APS spectra are simpler than those of the XAS ones. A careful
      interpretation of the spectra would lead to a characteristic and simple surface
      chemical analysis.

PMID- 20145320
TI  - ISO-Compliant calibration of energy and intensity scales of electron
      spectrometers.
AB  - The International Organization for Standardization (ISO) decided to establish a
      Technical Committee 201 (TC201) on the standardization of surface chemical
      analysis in 1991. Since then, TC201 has published 38 ISO standards. They concern
      the vocabulary, instrument specifications, pretreatments of specimen, the
      procedures for analysis, apparatus alignments, measurement conditions,
      quantification and reporting formats. In this paper, ISO standards on the
      calibration of energy and intensity scales of electron spectrometers are briefly
      introduced. Common Data Processing System is the software for assisting in using
      ISO standards, and its functions for the calibration of energy and intensity
      scales are also introduced.

PMID- 20145321
TI  - Effects of electron back-scattering in observations of cross-sectioned GaAs/AlAs
      superlattice with auger electron spectroscopy.
AB  - Cross-sections of GaAs/AlAs thin films prepared by cleavage of MBE-grown
      superlattices have been analyzed with Auger electron spectroscopy with a spatial
      resolution of 6 nm. Elemental distributions of Ga, Al, and As were clearly
      distinguished in line analysis as well as in two dimensional mapping for 50, 20,
      and 10 nm thin film structures. We have found an oscillation of Al KLL peak
      position between the two values while the peak positions of Ga LMM and As LMM
      remain constant. The origin of the Al KLL peak shift is a primary electron beam
      induced reduction of oxidized Al atoms formed during specimen preparation. The
      Auger spectra of Al oxide are generated by scattered electrons at regions with
      small amounts of electron dose, corresponding to AlAs areas further than 10 to 25
      nm from the primary beam. The intensity of the Al KLL peaks excited by scattered
      electrons from the 25 kV primary electron beam is about 10% of the Ga LMM peak
      intensity originating from the GaAs stripe.

PMID- 20145322
TI  - Non-destructive depth profiling of the activated Ti-Zr-V Getter by means of
      excitation energy resolved photoelectron spectroscopy.
AB  - Non-evaporable Ti-Zr-V ternary getters (NEGs) were studied by means of excitation
      energy resolved photoelectron spectroscopy (ERXPS). We attempted a quantitative
      study of the in-depth redistribution of the NEG components during activation. The
      samples were prepared ex-situ by DC magnetron sputtering on a stainless-steel
      substrate. The ERXPS measurements were carried out at two incident photoelectron
      beam angles at energies of 110, 195, 251, 312, 397 and 641 eV. Besides these
      photon energies, also standard X-ray photoelectron spectroscopy (XPS) was used at
      a photon energy of 1254 eV. We accumulated Ti 3s, Ti 3p, Ti 3d, V 3s, V 3p, V 3d,
      Zr 3p, Zr 3d, Zr 4s, Zr 4p, Zr 4d, C 1s, O 1s and O 2s photoelectron peak
      intensities as functions of the kinetic energies given to them. Under simplifying
      assumptions, Monte-Carlo calculations of the activated sample concentration
      profiles were performed to fit the measured spectra intensities. The results
      proved an in-depth redistribution of the components during the activation
      process. This way we also contributed to a further development of non-destructive
      depth profiling by electron spectroscopy techniques.

PMID- 20145323
TI  - Electron spectra line shape analysis of highly oriented pyrolytic graphite and
      nanocrystalline diamond.
AB  - The X-ray excited Auger electron spectroscopy (XAES), X-ray photoelectron
      spectroscopy (XPS) and elastic peak electron spectroscopy (EPES) methods were
      applied in investigating samples of nanocrystalline diamond and highly oriented
      pyrolytic graphite of various C sp(2)/sp(3) ratios, crystallinity conditions and
      grain sizes. The composition at the surface was estimated from the XPS. The C
      sp(2)/sp(3) ratio was evaluated from the width of the XAES first derivative C KLL
      spectra and from fitting of XPS C 1s spectra into components. The pattern
      recognition (PR) method applied for analyzing the spectra line shapes exhibited
      high accuracy in distinguishing different carbon materials. The PR method was
      found to be a potentially useful approach for identification, especially
      important for technological applications in fields of materials engineering and
      for controlling the chemical reaction products during synthesis.

PMID- 20145324
TI  - Analysis of ultra-thin HfO(2)/SiON/Si(001): comparison of three different
      techniques.
AB  - Composition depth profiling of HfO(2) (2.5 nm)/SiON (1.6 nm)/Si(001) was
      performed by three diffetent analytical techniques: high-resolution Rutherford
      backscattering spectroscopy (HRBS), angle-resolved X-ray photoelectron
      spectroscopy (AR-XPS) and high-resolution elastic recoil detection (HR-ERD). By
      comparing these results we found the following: (1) HRBS generally provides
      accurate depth profiles. However, care must be taken in backgroud subtraction for
      depth profiling of light elements. (2) In the standard AR-XPS analysis, a simple
      exponential formula is often used to calculate the photoelectron escape
      probability. This simple formula, however, cannot be used for the precise depth
      profiling. (2) Although HR-ERD is the most reliable technique for the depth
      profiling of light elements, it may suffer from multiple scattering, which
      deteriorates the depth resolution, and also may cause a large background.

PMID- 20145325
TI  - Development of the hard-X-ray angle resolved X-ray photoemission spectrometer for
      laboratory use.
AB  - This article reports development of a practical laboratory hard X-ray
      photoelectron spectroscopy (HXPS) system by combining a focused monochromatic Cr
      K(alpha) X-ray source, a wide angle acceptance objective lens and a high kinetic
      energy electron analyzer. The Cr K(alpha) source consists of a Cr target, a 15 kV
      focused electron gun, and a compact bent crystal monochromator. The X-ray spot
      size is variable from 10 microm (1.25 W) to 200 microm (50 W). A wide acceptance
      angle objective lens is installed in front of a hemispherical analyzer. The total
      resolution of 0.53 eV was obtained by Au Fermi-edge measurements. Angle
      acceptance of +/-35 degrees with angle resolution of 0.5 degrees was achieved by
      measuring Au 3d(5/2) peak through a hemicylinder multi-slit on an Au thin strip,
      in angle resolution mode. As the examples, silicon based multilayer thin films
      were used for showing the possibilities of deeper (larger) detection depth with
      the designed system.

PMID- 20145326
TI  - Contribution of Ni KLL Auger electrons to the probing depth of the conversion
      electron yield measurements.
AB  - The averaged attenuation length of emitted electrons with the conversion electron
      yield (CEY) method was evaluated for Ni films with the x-rays below and above the
      Ni K absorption edge. The evaluated attenuation length was 13.1 nm with the x
      rays below the Ni K absorption edge, and it became 24.0 nm with the contribution
      of Ni KLL Auger electrons that had the attenuation length of 78.1 nm. The probing
      depth of the CEY measurements are determined both the penetration depth of x-rays
      and the attenuation length of emitted electrons, and the modification of the
      probing depth was investigated with the grazing incidence condition. The glancing
      angle dependence of the CEY was compared with the model calculation, and the
      probing depth of around 1.6 nm was realized under the total reflection condition.
      The probing depth was controlled from 1.6 nm to the attenuation length by
      changing the glancing angle.

PMID- 20145327
TI  - Remarks on some reference materials for applications in elastic peak electron
      spectroscopy.
AB  - The quantification of results of electron spectroscopies, AES and XPS, requires
      knowledge of the inelastic mean free path (IMFP) of signal electrons in solids.
      This parameter determines the surface sensitivity of both techniques. There are
      two methods of determining the IMFPs that provide these parameters in agreement
      with the definition: (i) calculations based on the experimental optical data, and
      (ii) calculations based on measurements of the electron elastic backscattering
      intensity. The latter method requires the use of some reference material for
      which the IMFP is known. In 1999, an extensive analysis of the published IMFPs
      has been performed; the results indicated that there is a very good agreement
      between the calculated and measured IMFPs for four elemental solids: Ni, Cu, Ag
      and Au. The averaged IMFPs for these elements are known under the name of the
      recommended IMFPs. However, no preference among these four elements has been
      established. In the present work, an attempt is made to select an element for
      which the recommended IMFPs result in the best agreement between the calculated
      and measured intensities of elastic electron backscattering. For this purpose,
      the elastic backscattering intensity has been measured at eight electron energies
      varying from 200 to 1500 eV. At each energy, the intensity was measured over a
      wide range of emission angles from 35 degrees to 74 degrees . The experiments
      were accompanied with Monte Carlo calculations of the elastic backscattering
      probability for the same energies and experimental configurations. It has been
      found, from comparison, that the best agreement is observed for Au, and this
      element is thus recommended as the reference material. It has been shown that the
      shape of the emission angle dependence of the elastic backscattering intensity is
      noticeably influenced by the surface energy losses.

PMID- 20145328
TI  - A study of the cascade Auger process using a cluster calculation.
AB  - The Auger process on shallow levels, caused by the Auger process in deeper
      levels, called "cascade Auger process", were studied. From the measurement
      result, the cascade Auger process can be clearly observed by the excitation of X
      ray tubes instead of a synchrotron radiation source. Applying a theoretical
      investigation with a cluster calculation to the spectral change of the Ag
      M(VI,V)VV peak, it was theoretically shown that the cascade Auger process should
      be correct for explaining the observed spectral change. In addition, it pointed
      out the existence of a cascade Auger process caused by holes left by the Coster
      Kronig process on deeper levels. For the first time the measurement of this
      process was successful using X-ray tube excitation.

PMID- 20145329
TI  - The theoretical study of si core levels for the change of oxidation state.
AB  - The investigations of Si 1s and 2p photoelectron spectra of a poly-Si plate with
      natural oxide layers based on high energy excitation using X-ray tubes with three
      kinds of target (Mg K(alpha), Zr L(alpha) and Ag L(alpha)) and on the theoretical
      calculations using DV-Xalpha were presented. From the comparison between the
      shift values of Si 1s and 2p corresponding with the metal and oxide, it was found
      that 1s shift is larger than 2p shift. From the discussion on the cluster
      calculation, the data revealed that the direction of chemical shift is dominated
      by the change of the population of 3s/3p or 3d independently.

PMID- 20145330
TI  - A practical method for determining minimum detectable values in pulse-counting
      measurements.
AB  - The purpose of this paper is to propose a statistical method for determining
      minimum detectable values in a pulse-counting measurements. The output of x-ray,
      electron and ion-spectroscopy detectors is a series of pulses that vary in their
      arrival frequency according to a Poisson distribution. The analysis presented
      here relates this to a Normal distribution, making it consistent with the
      standards and methodology recommended by IUPAC and in the ISO 11843 series of
      international standards. The theory and limitations of doing this are presented
      using two types of approximations: a Simple approximation and a Square Root
      approximation. The variance, critical values of the response variables,
      capability of detection criteria and the minimum detectable values are then
      defined. Finally, the validity of the approximations is checked using
      experimental data. It is concluded that the methodology is accurate enough for
      practical use.

PMID- 20145331
TI  - Structure of ultra-thin diamond-like carbon films grown with filtered cathodic
      arc on Si(001).
AB  - The structure of 3 nm and 15 nm diamond-like carbon films, grown on Si(001) by
      filtered cathodic arc, was studied by angle-resolved X-ray photoelectron
      spectroscopy (ARXPS) and transmission electron microscopy (TEM). The ARXPS data
      was deconvolved by employing simultaneous-fitting, which allowed for a clear
      deconvolution of the Si 2p and C 1s spectra into their different chemical
      contributions. An analysis of the take-off angle dependence of the peak
      intensities allowed for an independent identification of the physical origin of
      the chemical species. It was shown that the C 1s peak at 283.3 eV and the Si 2p
      peak at 99.6 eV correspond to SiC, and that the C/Si interface of the 3 nm film
      consists of a stoichiometric approximately 1 nm SiC layer. To quantify the sp(3)
      sp(2) ratio it was necessary to take into account not only their associated C 1s
      XPS-peak intensities, but also their take-off angle dependence. The thickness of
      the films obtained through ARXPS closely agrees with cross-sectional TEM images.

PMID- 20145332
TI  - Evaluation of outermost surface temperature of silicon substrates during UV
      excited ozone oxidation at low temperature.
AB  - Using ultraviolet (UV)-excited ozone gas, we prepared high-quality SiO(2) films
      that can be used as gate dielectric films on poly-silicon or silicon wafers
      without sample heating. The UV-excited ozone gas was generated by UV irradiation
      of highly concentrated ozone gas. During the UV-excited ozone process, UV light
      irradiates the sample surface directly through the ozone gas. Then, the
      temperature at the sample surface is increased by UV-light absorption at the
      surface. Estimation of this surface temperature is important for understanding
      the oxidation mechanism. We estimated the surface temperature obtained during UV
      irradiation to be about 300 degrees C by investigating the temperature dependence
      of the oxidation rate for oxygen gas. We have previously determined that almost
      no thermal decomposition of ozone gas occurs at this temperature, and that oxygen
      gas does not oxidize the Si substrate. Therefore, we concluded that the only
      oxidation species in the UV-excited ozone process is UV-excited ozone O((1)D).

PMID- 20145333
TI  - X-ray fluorescence analysis of Cr(6+) component in mixtures of Cr(2)O(3) and
      K(2)CrO(4).
AB  - X-ray fluorescence analysis using Cr K(alpha) spectra was applied to the
      determination of the mixing ratio of Cr(6+) to (Cr(6+) + Cr(3+)) in several
      mixtures of K(2)CrO(4) and Cr(2)O(3). Because the powder of K(2)CrO(4) contained
      large particles that were more than 50 microm in diameter, it was ground between
      a pestle and a mortar for about 8 h. The coarse particles still remaining were
      removed by using a sieve with 325-mesh (44 microm) in order to reduce the
      difference in absorption effects between emissions from Cr(6+) and those from
      Cr(3+). The mixing ratio, K(2)CrO(4)/(K(2)CrO(4) + Cr(2)O(3)), of the five
      mixtures investigated is 0.50, 0.40, 0.20, 0.10, and 0.05 in weight,
      respectively. Each spectrum obtained was analyzed by decomposing it into two
      reference spectra, those of the two pure materials, K(2)CrO(4) and Cr(2)O(3),
      with a constant background. The results for the mixtures containing K(2)CrO(4) of
      more than 20 wt% are that the relative deviation from the true value is less than
      approximately 5%. On the other hand, when the content of K(2)CrO(4) decreases to
      less than 10 wt%, the relative deviation gets so large as 20 - 25%. The error
      coming from a peak separation of spectrum involved in our results were estimated
      by applying our method to five sets of data for each mixture computationally
      generated, taking into account the uncertainty in total counts of real
      measurements.

PMID- 20145334
TI  - Quantitative estimation methods for concentrations and layer thicknesses of
      elements using edge-jump ratios of X-ray absorption spectra.
AB  - This work concerns the development of quantitative estimation techniques using
      the K edge-jump ratio of X-ray absorption spectrum recorded through total
      electron-yield measurements. The three methods of calculation methods proposed
      here can be used to estimate (1) the bulk elemental composition of homogeneous
      solid materials, (2) the thickness of the thin layers, and (3) the amounts of
      atoms implanted by certain acceleration energies. The estimations are based on
      theoretical photoelectron cross sections of elements, the Auger electron
      effective range calculated using the stopping power of electrons, and the depth
      profiles of the elements.

PMID- 20145336
TI  - Towards a tailored use of eluted drugs for percutaneous coronary interventions.

PMID- 20145337
TI  - Controversies on obesity and CKD.

PMID- 20145338
TI  - Multidisciplinary approach to severe coronary artery disease.

PMID- 20145339
TI  - Role of adiponectin in cardiovascular protection.

PMID- 20145340
TI  - The entire coronary arterial system rather than just the culprit lesion should be
      evaluated in patients with acute coronary syndrome.

PMID- 20145341
TI  - Association of the functional variant in the 3-hydroxy-3-methylglutaryl-coenzyme
      a reductase gene with low-density lipoprotein-cholesterol in Japanese.
AB  - BACKGROUND: The association between single nucleotide polymorphisms (SNPs) at 3
      hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and low-density lipoprotein
      cholesterol (LDL-C) levels has been well replicated in genome-wide association
      studies (GWAS) of white populations. Recently, the common intronic SNP of HMGCR
      (rs3846662) has been reported to be a functional variant, influencing the
      alternative splicing of exon 13. The aim of this study was to examine the
      association between rs3846662 of HMGCR and the level of LDL-C in Japanese.
      METHODS AND RESULTS: Significant differences in LDL-C levels were observed among
      the genotypes of rs3846662 (P=0.0002 (n=2,686) and P=0.004 (n=2,110)) for the
      Suita and Ehime samples, respectively. The G allele of rs3846662 was associated
      with higher LDL-C levels (beta, 3.56; P=4.91x10(-5)). Consistent with this
      observation, the risk G allele at rs3846662 was more prevalent in subjects with
      myocardial infarction (MI) (n=701) than in subjects without MI (n=3,118); 0.559
      and 0.511 in MI cases and controls, respectively (nominal P=0.0038). The odds
      ratio adjusted for age, sex, diabetes, hypertension, and drinking and smoking
      habits was 1.15 (95% confidence interval 1.04-1.28; P=0.0075). CONCLUSIONS: The
      previously reported association of rs3846662 with LDL-C levels was replicated in
      the present Suita and Ehime samples. The LDL-associated SNP, rs3846662, appears
      to confer susceptibility to MI in Japanese.

PMID- 20145342
TI  - Clinical importance of adherence to treatment with eicosapentaenoic acid by
      patients with hypercholesterolemia.
AB  - BACKGROUND: Despite the risk of critical heart disease, poor adherence to
      treatment is common in patients with lifestyle-related diseases such as
      hypercholesterolemia. The association between adherence to treatment and clinical
      outcome was examined in JELIS (Japan EPA Lipid Intervention Study) and strategies
      for avoiding poor adherence were explored. METHODS AND RESULTS: Patients taking
      80% or more of the study medications were considered to exhibit good adherence.
      The primary endpoint was either sudden cardiac death or myocardial infarction.
      Adherence was lower in the eicosapentaenoic acid (EPA) + statin group (66.5%)
      than in the statin alone group (72.5%). In good adherers with previous coronary
      artery disease, EPA substantially reduced the risk compared with statin alone
      (hazard ratio 0.55, 95% confidence intervals 0.34-0.88, P<0.014). Furthermore,
      the clinical benefit of EPA + statin was significantly larger in patients with
      good adherence than in those with poor adherence (P=0.041). Finally, a 5-year
      risk prediction model constructed from the data indicated that complete adherence
      would lead to 51% reduction of risk compared with non-adherence. CONCLUSIONS:
      Good adherence to medication was associated with a lower cardiovascular risk than
      with poor adherence, and the assistance of a pharmacist is of great importance in
      achieving persistent adherence during treatment.

PMID- 20145343
TI  - Diagnosis and treatment of endothelial dysfunction in cardiovascular disease.
AB  - Vascular endothelial dysfunction reflected by reduced nitric oxide (NO)
      availability is certainly the causative factor or promoting mechanism of
      arteriosclerosis. It is necessary to detect endothelial dysfunction at an early
      stage using appropriate methods, and to choose a treatment for the recovery of
      endothelial function. There are nonpharmacological and pharmacological therapies
      to attain endothelial repair. The former includes body weight reduction, aerobic
      exercise, and restriction of salt intake, while the latter includes the use of
      renin-angiotensin system inhibitors, calcium antagonists, some types of beta
      blockers, statins, erythropoietin, tetrahydrobiopterin, and antioxidants. These
      therapies are intended to increase NO synthase activity and NO release, inhibit
      NO degradation, and enhance the activity of endothelial progenitor cells.

PMID- 20145344
TI  - Difference in neointimal proliferation between ruptured and non-ruptured segments
      after bare metal stent implantation.
AB  - The difference in neointimal stent coverage (NSC) between ruptured segments and
      adjacent nonruptured segments in infarct-related lesions (IRL) of acute
      myocardial infarction after bare metal stent (BMS) implantation was evaluated
      using coronary angioscopy. Serial angioscopic observations were performed for 19
      IRLs immediately after the implantation of a BMS and at 1-month and 6-month
      follow-up. Stented segments were divided into the ruptured segment and the
      nonruptured segment based on the presence of a thrombus. The grade of NSC was
      divided into 0 = complete exposure, 1 = partial coverage, or 2 = complete
      coverage. The grade of plaque color was classified semiquantitatively as 0 =
      white, 1 = light yellow, or 2 = intense yellow. The existence of a thrombus was
      also determined. The grade of NSC in the ruptured segment was lower than that of
      the nonruptured segment at each follow-up. The grade of plaque color at the 1
      month follow-up was higher in the ruptured segment than in the nonruptured
      segment. At 6 months, the grade of plaque color was similar between the ruptured
      and nonruptured segments. In all cases, thrombi existed in the ruptured segments
      immediately after stenting. Although thrombi still remained frequently at 1
      month, most had disappeared at the 6-month follow-up. Neointimal proliferation of
      the ruptured segment in IRL advanced slowly in comparison to the adjacent
      nonruptured segment. The presence of an atherosclerotic yellow plaque and a
      thrombus may affect the delayed neointimal coverage after BMS implantation.

PMID- 20145345
TI  - Effects of omeprazole on the antiplatelet activity of clopidogrel.
AB  - Clopidogrel is used with aspirin as a standard combined treatment in patients
      with acute coronary syndrome. A proton pump inhibitor (PPI) is often administered
      to patients receiving antiplatelet therapy. However, PPI use with clopidogrel was
      recently shown to result in increased risk of major cardiovascular events when
      compared to clopidogrel use alone. Therefore, the aim of the present study was to
      evaluate the effects of omeprazole, a PPI, on the antiplatelet effect of
      clopidogrel.We divided 20 healthy volunteers into 2 groups (n = 10 each). Twenty
      four hours after a 300 mg loading dose of clopidogrel, one group received a
      dosage of 75 mg/day of clopidogrel and a placebo for 14 days, followed 3 weeks
      later by the same protocol but with coadministration of 75 mg/day clopidogrel and
      20 mg/day omeprazole instead. The other group received the same treatment but in
      reverse order. Antiplatelet activity was assessed in terms of the P2Y12 reaction
      unit (PRU) and percentage inhibition using a VerifyNow P2Y12 assay system.The PRU
      of the omeprazole-treated subjects was significantly higher than that of the
      omeprazole-untreated subjects on day 14 (281.3 +/- 54.0 versus 240.0 +/- 72.2, P
      = 0.048). The percentage inhibition showed a decrease after the 14-day omeprazole
      treatment (22.7 +/- 29.9% versus 35.1 +/- 18.7%, P = 0.014). Consequently,
      omeprazole reduces the antiplatelet effect of clopidogrel, suggesting that
      careful treatment planning is required when administering omeprazole to patients
      on clopidogrel therapy.

PMID- 20145346
TI  - Right ventricular histological substrate and conduction delay in patients with
      Brugada syndrome.
AB  - The reported pathogenesis of Brugada syndrome is phase 2 reentry resulting from
      shortening of the epicardial action potential duration at the right ventricular
      outflow tract (RVOT). However, several studies have revealed a high incidence of
      ventricular late potentials and high rate of ventricular fibrillation (VF)
      induced by programmed ventricular stimulation (PVS). The aim of the present study
      was to evaluate the role of slow conduction at the RVOT for the initiation of VF
      by PVS and any underlying pathological conditions in Brugada syndrome.
      Endocardial mapping of the RVOT and endomyocardial biopsy of the right ventricle
      were performed in 25 patients with Brugada syndrome with inducible VF. Late
      potentials were positive in 11 of the 25 (44%) patients. Low-amplitude fragmented
      and delayed electrograms were recorded at the RVOT in 13 of 18 (72.2%) patients.
      Histologic examination of the biopsy samples revealed fatty tissue infiltration,
      interstitial fibrosis, lymphocyte infiltration, and/or myocyte disorganization in
      13 patients. Slow conduction at the RVOT may contribute to the induction of VF by
      PVS in Brugada syndrome. Various pathomorphologic changes may contribute to slow
      conduction at the RVOT.

PMID- 20145347
TI  - Relationship between CHADS2 score and ischemic stroke during rhythm control
      therapy for paroxysmal atrial fibrillation.
AB  - The CHADS2 score has been proposed for stratifying patients with nonvalvular
      atrial fibrillation (NVAF) according to the risk of thromboembolism in the
      AHA/ACC/ESC guidelines. However, there is little information about its usefulness
      for predicting the long-term risk of ischemic stroke in Japanese patients with
      paroxysmal AF. We retrospectively evaluated the incidence of ischemic stroke and
      the efficacy of anticoagulant therapy in paroxysmal AF patients on rhythm control
      therapy who were stratified by their CHADS2 score. The subjects were 334 NVAF
      atients (229 men and 105 women, mean age, 68 +/- 12 years, mean follow-up period,
      60 +/- 35 months) who were categorized into low risk (score 0), moderate risk (1
      or 2), and high risk (3 or more) groups for thromboembolism. The low, moderate,
      and high risk groups accounted for 34%, 50%, and 16% of the patients,
      respectively. Among 257 patients without warfarin therapy, the annual rate of
      symptomatic ischemic stroke was 0.6% in the score 0 group, 0.5% in the score 1
      group, 3.1% in the score 2 group, and 9.6% in the score 3 or more group. Among 77
      patients treated with warfarin (target PT-INR: 1.6-3.0), the stroke rate was 0%
      in the score 0 group, 0% in the score 1 group, 1.4% in the score 2 group, and
      6.6% in the score 3 or more group. The annual rate of ischemic stroke was 0.88%
      in patients treated with warfarin versus 2.67% in those without warfarin, or a
      decrease in risk of 68% with warfarin (P < 0.01). In Japanese patients with
      paroxysmal AF, the CHADS2 score is useful for predicting the risk of ischemic
      stroke. Anticoagulant therapy is needed to prevent ischemic stroke in patients
      with paroxysmal AF, especially those who have a CHADS2 score of 2 or more.

PMID- 20145348
TI  - High homocysteine levels predict the recurrence of atrial fibrillation after
      successful electrical cardioversion.
AB  - Recent data suggest that elevated plasma levels of homocysteine could be
      associated with atrial fibrillation (AF). The aim of our study was to investigate
      whether elevated plasma Hcy levels were predictive of the recurrence rate of AF
      after successful electrical cardioversion. Eighty-three patients (63 +/- 12
      years, 61.4% men) with persistent AF lasting at least 7 days were included after
      successful electrical cardioversion. Echocardiography and plasma homocysteine
      assay were performed prior to cardioversion and patient baseline characteristics
      were obtained. Patients were monitored for a period of 18 months. The patients
      were divided into two groups using a cut-off value for the last quartile of
      plasma homocysteine concentration (> 14.4 micromol/L). Kaplan Meier analysis
      showed a statistically significant difference in AF recurrence rates between both
      groups after 18 months (P = 0.02, log rank test). Cox proportional hazards
      multivariate analysis showed that predictors of AF recurrence were the duration
      of AF (OR 1.05, 95% CI 1.02-1.08, P = 0.00), treatment with amiodarone (OR 0.39,
      95% CI 0.21-0.72, P = 0.00), and homocysteine level < or = 14.4 micromol/L (OR
      0.39, 95% CI 0.21-0.73, P = 0.00). We found that the homocysteine levels
      determined prior to electrical cardioversion can predict recurrence of AF after
      successful restoration of sinus rhythm.

PMID- 20145349
TI  - Clinical course of arrhythmogenic right ventricular cardiomyopathy in the era of
      implantable cardioverter-defibrillators and radiofrequency catheter ablation.
AB  - This study investigated the clinical course of arrhythmogenic right ventricular
      cardiomyopathy (ARVC) patients and in particular evaluated the contribution of
      radiofrequency catheter ablation (RFCA) and an implantable cardioverter
      defibrillator (ICD) to the treatment of ARVC. ARVC is a myocardial disorder and a
      cause of sudden cardiac death due to ventricular tachycardia (VT). Little is
      known about its prognosis in Japanese ARVC patients. Thirty-five ARVC patients
      were studied. Mean age of patients whose onset of ARVC was congestive heart
      failure (CHF) (66.0 +/- 4.0 years) was significantly higher than those whose
      onset was VT (44.5 +/- 14.8 years, P < 0.05). ARVC patients with CHF onset showed
      significantly higher death rates compared to those with VT onset. ICD treatment
      significantly reduced episodes of hospitalization due to VT (0.1 +/- 0.4
      episodes) in comparison to treatment by RFCA (1.7 +/- 2.2 episodes, P < 0.03).
      RFCA treatment did not reduce recurrence of VT in the follow-up period. ICD
      therapy showed comparable mortality to RFCA treatment. The prognosis of ARVC with
      CHF onset is poor. ICD therapy significantly reduced hospitalization due to VT
      compared with RFCA treatment. ICD implantation in combination with medication may
      be a better treatment for ARVC.

PMID- 20145350
TI  - Long-term exercise-training improves QT dispersion in the metabolic syndrome.
AB  - Increased QT dispersion (QTd) is a marker of myocardial electrical instability
      and predicts ventricular arrhythmias and sudden cardiac death. Exercise training
      (ET) has been shown to reduce both QTd and cardiovascular mortality in various
      populations. Patients with metabolic syndrome (MS) have been shown to have
      increased QTd. The effect of ET on QTd in MS patients however is unknown. We
      sought to assess the effect of a long-term (> or = 6 months) ET program on QTd
      parameters in MS patients with and without coronary heart disease (CHD). Fifteen
      CHD and 31 non-CHD patients with MS (mean age, 64 +/- 7 and 57 +/- 9 years,
      respectively) were identified at entry into identical ET programs. MS was defined
      using modified National Cholesterol Education Program criteria. A control group
      consisted of 8 MS patients with CHD (mean age, 65 +/- 6 years). Ventricular
      repolarization (QT dispersion = QTd, standard deviation of QT = SDQT, relative
      dispersion of QT = RDQT, QT corrected dispersion = QTcd), metabolic and exercise
      parameters were measured before and after ET. Program duration was over 9 months
      (312 +/- 100 versus 284 +/- 101 days in CHD and non-CHD cohorts, P = NS). QTd
      decreased in both ET groups (QTd pre versus post = 66 versus 56 ms in CHD group,
      P < 0.01; 58 versus 51 ms in non-CHD group, P < or = 0.01). Other ventricular
      repolarization parameters also improved significantly in both MS groups following
      ET, but remained unchanged in the control group. A long-term ET program improves
      QTd in patients with MS with and without CHD.

PMID- 20145351
TI  - Papillary muscle head approximation for the treatment of mitral valve
      regurgitation combined with aortic valve disease.
AB  - We initiated an original papillary muscle head approximation procedure, commonly
      known as Sandwich plasty, for the treatment of ischemic mitral regurgitation
      (MR). In this study, we evaluated the appropriateness of this procedure for
      functional MR associated with aortic valve disease. Fifteen patients who had
      undergone Sandwich plasty combined with aortic valve surgery were included in
      this study. The mean age of the patients was 69 years. Predominant aortic valve
      diseases were regurgitation in 8 patients and stenosis in 7 patients. Aortic
      valve replacement was performed in 14 patients and David surgery in one. The
      mitral valve was approached through the aortic annulus in 9 patients (the
      transaortic group). Six other patients with mitral valve annulus of 30 mm or
      larger underwent concomitant mitral ring-annuloplasty through a left atrial
      incision (the LA group). The tenting height of the mitral valve and left
      ventricle diastolic diameter significantly decreased after surgery in both
      groups. After surgery, residual moderate or mild MR was detected in two patients
      in the transaortic group. In the LA group, residual mitral regurgitation was not
      detected. In the follow-up study, prominent MR occurred in two patients in the
      transaortic group. The MR free rate two years after surgery was 83% in the total
      patient population. Sandwich plasty was simple and effective in the treatment of
      functional mitral regurgitation combined with aortic valve surgery. A transaortic
      approach is effective in obviating a separate left atriotomy and reducing
      operation time.

PMID- 20145352
TI  - Plasma adiponectin levels and left ventricular remodeling in hypertrophic
      cardiomyopathy.
AB  - Adiponectin, which is an adipose-derived protein with antiatherosclerogenic
      activities, has been reported to be elevated in patients with heart failure.
      However, there are no reports on the significance of adiponectin in patients with
      hypertrophic cardiomyopathy (HCM). The purpose of this study was to elucidate the
      clinical significance of plasma adiponectin levels in HCM patients. Clinical
      characteristics, echocardiographic parameters, and levels of plasma B-type
      natriuretic peptide (BNP) and adiponectin were evaluated in 106 HCM patients. The
      plasma adiponectin levels were 10.8 +/- 6.3 (range, 2.7-37.3) microg/mL. Plasma
      adiponectin levels were positively related to age and inversely related to body
      mass index (BMI). Among echocardiographic parameters, % fractional shortening (r
      = -0.20, P = 0.03) and maximum LV wall thickness (r = -0.23, P = 0.02) were
      inversely related to plasma adiponectin levels. A significant correlation between
      plasma adiponectin levels and BNP levels was also observed (r = 0.27, P = 0.005).
      In multivariate analysis, BMI, % fractional shortening, and plasma BNP levels
      were independent predictors of plasma adiponectin levels. Plasma adiponectin
      levels are associated with impaired LV systolic function in HCM patients, but not
      with the LV outflow gradient. Together with BNP, adiponectin can be a useful
      biomarker for assessing disease severity in HCM patients.

PMID- 20145353
TI  - Stretched size of atrial septal defect predicted by intracardiac
      echocardiography.
AB  - The stretched size of an atrial septal defect (ASD) is important for device
      selection during transcatheter closure. However, balloon sizing carries potential
      risks such as hypotension, bradycardia, or laceration of the atrial septum. The
      aim of the present study was to investigate the accuracy of the predicted
      stretched size of ASD by intracardiac echocardiography (ICE). From December 2004
      to November 2007, 136 consecutive patients with single secundum type ASD
      undergoing transcatheter closure of their defect using the Amplatzer septal
      occluder under ICE guidance were enrolled for analysis. There were 43 males and
      93 females. The age ranged from 2.2 to 79.1 years with a median age of 13.4
      years. The body weight ranged from 12.1 to 93.2 kg with a median body weight of
      45.8 kg. The stretched size of ASD measured by a sizing plate was considered as
      the standard. ASD sizes measured by ICE in bicaval and short-axis views predicted
      the stretched size by formulae derived from linear regressions. The predicted
      stretched sizes obtained using 2 formulae, 1.34 x radicalbicaval xshort axis
      (formula 1) and 1.22 x larger diameter (formula 2), exhibited good agreement with
      the standard stretched size with Kappa values of 0.91 and 0.90, respectively. The
      accuracy rate of predicted stretched sizes within 2 mm, 3 mm, and 4 mm range of
      the standard size were 32.8%, 45.4%, and 57.7% (formula 1) and 33.1%, 50%, and
      63.2% (formula 2). The stretched size of ASD predicted by ICE exhibited good
      agreement with the standard stretched size. This prediction provides helpful
      information, especially if balloon sizing cannot be adequately performed.

PMID- 20145354
TI  - Effects of raloxifene on brachial arterial endothelial function, carotid wall
      thickness, and arterial stiffness in osteoporotic postmenopausal women.
AB  - The beneficial effects of raloxifene, a selective estrogen receptor modulator, on
      cardiovascular risks and events have been investigated. Brachial arterial flow
      mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and pulse
      wave velocity (PWV) have been widely used in clinical settings as surrogate
      markers of atherosclerosis. This study investigated the simultaneous effects of
      raloxifene on brachial arterial FMD, carotid IMT, and PWV in osteoporotic
      postmenopausal women. A total of 31 postmenopausal women with osteoporosis or
      osteopenia were divided into 2 groups: a raloxifene group (n = 15; mean age +/-
      SD, 66.1 +/- 8.2 years) was treated with raloxifene hydrochloride (60 mg/day)
      orally for 12 months, and an untreated control group (n = 16; 64.1 +/- 7.8
      years). Brachial arterial FMD, carotid IMT, and brachial-ankle PWV (baPWV) were
      measured at baseline and at 12 months after the start of the study. The brachial
      arterial FMD increased significantly, from 4.5 +/- 1.8% to 9.2 +/- 3.0%, in the
      raloxifene group (P < 0.01) but did not change in the control group.
      Nitroglycerin-induced vasodilatation did not change in either group. The carotid
      IMT decreased significantly, from 0.82 +/- 0.15 mm to 0.72 +/- 0.11 mm, in the
      raloxifene group (P < 0.01) but did not change in the control group. The baPWV
      did not change in either group. In conclusion, raloxifene may have beneficial
      effects on brachial arterial endothelial function and carotid wall thickness in
      osteoporotic postmenopausal women.

PMID- 20145355
TI  - Possible contribution of ischemia of the conus branch to induction or
      augmentation of Brugada type electrocardiographic changes in patients with
      coronary artery disease.
AB  - Recent evidence suggests an association between vasospastic angina and Brugada
      syndrome. Here we present two cases of coronary artery disease who presented with
      ECG abnormalities which might have been provoked or enhanced by ischemia of the
      conus branch of the right coronary artery. The 12-lead ECGs demonstrated normal
      sinus rhythm in these two cases. Interestingly, a saddle back or coved type ST
      segment elevation in leads V1-V3 was documented either in the percutaneous
      transluminal angioplasty procedure of the proximal right coronary artery or with
      an intracoronary acetylcholine (Ach) administration into the right coronary
      artery. These Brugada type ECG changes were restored to the baseline ECG waveform
      after improvement in the ischemia. In the second case, vasospasms of the conus
      branch of the right coronary artery were associated with a coved type ST segment
      elevation in leads V1 to V2. We discuss the possible interaction between ischemia
      caused by conus branch lesions and Brugada type electrocardiographic changes.

PMID- 20145356
TI  - Successful catheter ablation of atrial tachycardia and atrial fibrillation in
      persistent left superior vena cava.
AB  - Atrial tachycardia (AT) and atrial fibrillation (AF) were observed in a 21-year
      old male who had a history of patch closure for an atrial septal defect (ASD) at
      the age of 5 and a persistent left superior vena cava (LSVC). During
      electrophysiologic study, atrial extrastimuli reproducibly induced AT which
      spontaneously terminated or changed into AF. Electroanatomical mapping revealed
      focal AT arising from the floor of the proximal LSVC. Radio- frequency
      applications within LSVC targeted to the earliest activation site of AT as well
      as the complex fractionated potential eliminated both AT and AF without trans
      septal puncture.

PMID- 20145357
TI  - Insulin resistance and prevalence of prehypertension and hypertension among
      community-dwelling persons.
AB  - AIM: There are few data focusing on the effect of insulin resistance on a new
      risk category of prehypertension (120-139 mmHg systolic and/or 80-89 mmHg
      diastolic blood pressure) recently established by The Seventh Report of the Joint
      National Committee on High Blood Pressure (JNC-7). We aimed to determine whether
      insulin resistance was associated with a risk for prehypertension and
      hypertension. METHODS: Of 3,164 (34.6% of 9,133 adults aged 19 to 90 years)
      adults at the community-based annual medical check-up, study participants without
      a clinical history of stroke, transient ischemic attack, myocardial infarction,
      angina, or renal failure (567 men aged 57+/-14 (mean+/-standard deviation);
      range, 20-84) years and 702 women aged 59+/-12; 21-88 years) were recruited. We
      examined the cross-sectional relationship between insulin resistance, which was
      evaluated by homeostasis of minimal assessment of insulin resistance (HOMA-IR)
      and normotension, prehypertension, or hyper-tension using the JNC-7 criteria.
      RESULTS: The HOMA-IR correlated significantly with systolic (r=0.171) and
      diastolic (r=0.170) blood pressures. Triglycerides >or=150 mg/dL, HDL-C <40
      mg/dL, metabolic syndrome, serum uric acid >or=7.0 mg/dL, and HOMA-IR >or=2.5
      showed the highest crude odds ratio (OR) for progression from normotension to
      prehypertension, and >or=65 years, FBG >or=110 mg/dL, metabolic syndrome, and
      HOMA-IR >or=2.5 showed the highest crude OR for progression from normotension to
      hypertension. Multivariate logistic regression analysis showed that HOMA-IR was
      independently associated with the presence of prehypertension and hypertension.
      CONCLUSIONS: Insulin resistance was significantly associated with prehypertension
      as well as hypertension in the general population.

PMID- 20145358
TI  - Adipokines in periaortic and epicardial adipose tissue: differential expression
      and relation to atherosclerosis.
AB  - AIM: Adipokines are protein products of adipose tissue with paracrine and
      endocrine actions, which have been implicated in the pathogenesis of
      cardiovascular disease. Locally produced adipokines, especially by
      periadventitial adipose tissue, may affect vascular physiology and pathology. We
      investigated the expression of adiponectin, visfatin, leptin and novel adipokines
      chemerin and vaspin in human periaortic and epicardial adipose tissue, as well as
      their correlation to aortic and coronary atherosclerosis. METHODS: Standard
      immunohistochemical staining for the adipokines was performed on samples of human
      periaortic, pericoronary and apical epicardial adipose tissue. Atherosclerotic
      lesions of the adjacent vascular wall were assessed using the AHA classification.
      RESULTS: Adipokines were expressed in periadventitial and apical epicardial
      adipose tissue and - except for adiponectin - in vascular smooth muscle cells and
      foam cells in atherosclerotic lesions. Aortic atherosclerosis was positively
      correlated with chemerin, vaspin, visfatin and leptin periaortic fat expression.
      Coronary atherosclerosis was positively correlated with chemerin and visfatin
      pericoronary fat expression. Adipose tissue adiponectin expression was negatively
      correlated to atherosclerosis in both locations. Expression of adipokines in
      apical epicardial fat was not associated with atherosclerosis. CONCLUSIONS: Our
      results show: a) a different expression pattern of adiponectin, visfatin, leptin,
      chemerin and vaspin in periaortic, pericoronary and apical epicardial adipose
      tissue, b) a correlation of these adipokines with either aortic or coronary
      atherosclerosis or both in a pattern characteristic for each adipokine and
      suggest that locally produced adipokines might differently affect the
      atherosclerotic process in different locations.

PMID- 20145359
TI  - [How should we do to make JSRT better: science meeting and education system].

PMID- 20145360
TI  - [A new acquisition method with pacemaker resetting of coronary multidetector-row
      computed tomography for reduction of radiation dose in patients with pacemaker].
AB  - We proposed a new acquisition method of coronary MDCT achieved by pacing rate
      resetting and/or propranolol or verapamil injection in patients with a pacemaker.
      Coronary MDCT was undertaken in 57 patients with a pacemaker (DDD: 51, VVI: 6)
      and in 2975 patients with sinus rhythm as control using Aquilion 64 (Toshiba).
      Pacing rate was reset to 60 beats per minute (bpm) in DDD, and spontaneous beats
      were suppressed by propranolol injection. Pacing rate was reset to 70 bpm in
      atrial fibrillation with VVI, and spontaneous beats were suppressed by verapamil
      injection. Coronary MDCT was undertaken using as high a beam pitch (BP) as
      possible. When spontaneous beats were not suppressed, we selected the optimal
      gantry speed and BP to get the highest temporal resolution. Image quality makes
      no significant difference between pacemaker and sinus rhythm. When spontaneous
      beats were completely suppressed (all pacing), mean radiation dose and
      acquisition time, respectively, decreased by 33.0% and 35.2% in DDD compared with
      the method recommended by Heart Navi (by Toshiba), and they decreased by 38.1%
      and 25.9%, respectively, in VVI compared with the method recommended by Heart
      Navi. We could not estimate coronary stenosis in the proximal right coronary
      artery by lead artifacts in 30% of DDD pacemakers. In conclusion, the new method
      is useful for not only reducing radiation dose and acquisition time, but also for
      maintaining image quality in patients with a pacemaker.

PMID- 20145361
TI  - [Application of the grayscale standard display function to general purpose liquid
      crystal display monitors for clinical use].
AB  - Interpretations of medical images have been shifting to soft-copy readings with
      liquid-crystal display (LCD) monitors. The display function of the medical-grade
      LCD monitor for soft-copy readings is recommended to calibrate the grayscale
      standard display function (GSDF) in accordance with the guidelines of Japan and
      other countries. In this study, the luminance and display function of five models
      of eight general purpose LCD monitors were measured to gain an understanding of
      their characteristics. Moreover, the display function (gamma 2.2 or gamma 1.8) of
      general purpose LCD monitors was converted to GSDF through the use of a look-up
      table, and the detectability of a simulated lung nodule in the chest x-ray image
      was examined. As a result, the maximum luminance, contrast ratio, and luminance
      uniformity of general purpose LCD monitors, except for one model of two LCD
      monitors, met the management grade 1 standard in the guideline JESRA X-0093-2005.
      In addition, the detectability of simulated lung nodule in the mediastinal space
      was obviously improved by converting the display function of a general purpose
      LCD monitor into GSDF.

PMID- 20145362
TI  - [Overview of the infant body part photography condition using 16-rows
      multidetector CT].
AB  - In infant CT scans, it is important to minimize radiation exposure without
      lowering the quality of the diagnosis. Therefore, appropriate parameters for
      infant CT scan should be considered at each institute. In order to determine
      parameters for infant body CT, we measured the physical characteristics of our
      current CT machine and evaluated scan parameters as S.D. below 10 on the basis of
      literature recommendations, which say that we should adopt S.D. of the liver when
      treated with a radiation exposure dose in an adult abdominal CT scan. As a
      result, the ideal parameters were 90 kV tube voltage, ultra fast detail
      resolution, B kernel, and Eff.mAs value calculated from patient body width.
      Infant body CT scans with the mentioned parameters resulted in an S.D. below 10,
      and this is thought to be applicable to further examinations.

PMID- 20145363
TI  - [Effects of transmission scan protocol and attenuation correction method on
      normal database of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) brain positron
      emission tomography study].
AB  - Although post-injection transmission scan (POST-TS) after 2-[(18)F]fluoro-2-deoxy
      D-glucose ((18)F-FDG) injection[A1] is useful for short examination times, the
      emission count of (18)F-FDG[A2] in the regional brain area was not completely
      subtracted with use of the POST-TS method. The purpose of this study was to
      investigate the effect of POST-TS and attenuation correction (AC) methods on the
      normal database (NDB). A 10 min pre-injection transmission scan (PRE-TS) was
      performed before (18)F-FDG[A3] was injected in eighteen normal volunteers. A 10
      min POST-TS was then conducted beginning 40 min after (18)F-FDG[A4] injection,
      followed by a 10 min 2-dimentional emission scanning. To reconstruct each image
      of normal volunteers, the reconstruction was performed using the filtered back
      projection (FBP) method and the ordered subsets expectation maximization (OSEM)
      method, with transmission-based measured attenuation correction (MAC) and the
      segmented attenuation correction (SAC) technique. Subtraction images of NDB with
      PRE-TS or POST-TS were evaluated using 3D-SSP. A phantom study was also performed
      in addition to a human study, and assessment was by region of interests and
      profile curves. NDB images with POST-TS were significantly lower in the bilateral
      frontal lobes and higher in the parietal lobes and occipital lobes, including the
      precuneus, than those with PRE-TS, regardless of the different AC and
      reconstruction algorithms. Therefore, we have to be careful to confirm not only
      emission scan methods and reconstruction algorithms, but also TS methods and AC
      methods in the NDB. It will be best to perform PET examinations using the same TS
      methods and AC methods between NDB and patients.

PMID- 20145364
TI  - [Development of a prevention of body movement fixation appliance in leg digital
      subtraction angiography].
AB  - In the peripheral angiography to evaluate blood flow below the knee levels in
      patients with arteriosclerosis obliterans, a motion artifact occurs as a result
      of body movements of a patient in normal fixation. This sometimes makes a correct
      evaluation difficult. Therefore, we developed a fixed appliance which can
      restrain body movement without affecting image quality and blood flow in digital
      subtraction angiography of a leg. The appliance is filled with the styrofoam of 1
      mm diameter in a sealed bag, after air is aspirated from inside the bag. The
      appliance is stiffened to fit the shape of the crus. We measured signal to noise
      ratio / contrast to noise ratio / a resolution limit by visual evaluation to
      examine the influence of the image before and after usage of this appliance. In
      addition, the blood velocity of the dorsalis artery in ultrasound was measured to
      examine the effect on the blood flow. As a result, the fixed appliance did not
      affect blood flow in peripheral angiography to evaluate the clinical
      significance, the usual 5-point evaluate scale was used. The scale was
      significantly improved (p <0.01) after usage of this appliance. The newly
      developed fixed appliance for digital subtraction angiography of a leg is useful
      to avoid motion artifacts in clinical settings.

PMID- 20145365
TI  - [JSRT honorary member "Mr. Hiroshi Hashimoto"].

PMID- 20145366
TI  - [Clinical practices of IGRT in USA].

PMID- 20145367
TI  - [2. The production of X rays--interactions of electrons with the target--].

PMID- 20145369
TI  - [Detective quantum efficiency (DQE)].

PMID- 20145370
TI  - [Fundamental of medical image processing with personal computer system--nuclear
      medicine technology--].

PMID- 20145371
TI  - [Evaluation and problem of cone beam CT in angiography. 1. 3D-angiography].

PMID- 20145372
TI  - [Research of the header information and image properties in digital imaging and
      communication in medicine (DICOM) format of general radiography fields].

PMID- 20145373
TI  - [Survey of states of introduction and safety assurance of medical systems etc. in
      the 2008 fiscal year--part 2--].

PMID- 20145374
TI  - Glycoconjugate residues in a subpopulation of feline taste cells.
AB  - There have been a number of studies which have categorized cells of feline taste
      buds: Types I, II, III and IV; however, few studies have examined whether feline
      taste bud cell types differ from each other histochemically. The goal of the
      present study is to figure out what kinds of glycoconjugates correspond to the
      four different types of cells in the taste bud. We have detected glycochains by
      lectin histochemistry. We have also identified Types II and III by
      immunohistochemistry. Then, we combined lectin histochemistry and
      immunohistochemistry to determine which types of cells have which glycochains. In
      addition, we have compared these reactions in different papillae in the oral
      cavity: circumvallate papillae, fungiform papillae and epiglottises. Our results
      demonstrated that glycoconjugates showed a variety of distributions among cells
      in these papillae, although immunopositive reactions of the proteins involved in
      the taste transduction showed similar distributions in the taste buds in these
      papillae. Amongst all, N-acetyllactosamine was the most prominently detected
      glycoconjugate residue in a subpopulation of Type II (receptor) cells and Type
      III (pre-synaptic) cells. Our findings suggest that 1) Different localization of
      glycol-residues in taste buds might be owing to the possibility that different
      types of cells need different types of glycoconjugates, possibly for the function
      of cells in the taste buds, and 2) N-acetyllactosamine might play some roles in
      taste sensation perception and their transfer by Type II and III cells.

PMID- 20145376
TI  - A comparison of the antibody responses between specific pathogen-free and
      commercial layers immunized with an influenza vaccine prepared from inactivated
      non-pathogenic H5N1 virus by single shot.
AB  - It is known that antibody responses in chickens against invading organisms or
      antigens are considerably different among different lines. Thus, an avian
      influenza vaccine was prepared from inactivated whole particles of the virus of
      non-pathogenic strain A/duck/Hokkaido/Vac-1/04 (H5N1) using an oil adjuvant
      containing anhydromannitol-octadecenoate-ether and injected intramuscularly into
      each ten 10-week-old specific pathogen-free (SPF) white leghorn chickens and
      commercial layers of Julia and Boris-Brown to obtain comparative data for
      antibody responses until 6 weeks after vaccination. Despite significant partial
      differences of antibody titer between the chicken lines, this study clearly
      showed that the vaccine induced good and sufficient antibody response in both SPF
      chickens and commercial layers.

PMID- 20145375
TI  - Angiotensin II enhances interleukin-1 beta-induced MMP-9 secretion in adult rat
      cardiac fibroblasts.
AB  - Cardiac fibroblasts play important roles during the cardiac remodeling through
      the secretion of matrix metalloproteinase (MMP)-9. Inflammatory cytokine,
      interleukin (IL)-1beta induces MMP-9 secretion in cultured cardiac fibroblasts.
      Angiotensin II is well known to play pivotal roles in cardiac remodeling, but the
      effect of angiotensin II on MMP-9 secretion in cardiac fibroblasts has not been
      fully clarified. In the present study, we investigated the effect of angiotensin
      II on basal and IL-1beta-induced MMP-9 secretion in adult rat cardiac
      fibroblasts. MMP-9 protein secreted into culture medium, and phosphorylation of
      nuclear factor (NF)-kappaB, c-Jun NH(2)-terminal kinase (JNK), and extracellular
      signal-regulated kinase (ERK) in cell lysates were measured by Western blotting.
      Angiotensin II (1 nM, 24 hr) alone-treatment did not induce MMP-9 secretion.
      However, angiotensin II significantly enhanced IL-1beta (4 ng/ml, 24 hr)-induced
      MMP-9 secretion. Telmisartan (10 nM), an angiotensin II type 1 receptor (AT1R)
      antagonist, significantly suppressed the enhancement of IL-1beta-induced MMP-9
      secretion by angiotensin II, whereas PD123319 (10 nM), an angiotensin II type 2
      receptor antagonist, was ineffective. IL-1beta (4 ng/ml, 10 min) induced
      phosphorylation of NF-kappaB, JNK, and ERK. Angiotensin II augmented the IL-1beta
      induced phosphorylation of ERK but not NF-kappaB and JNK. PD98059 (50 microM), a
      selective inhibitor of ERK pathway, inhibited the angiotensin II enhancement of
      IL-1beta-induced MMP-9 secretion. These results suggest that angiotensin II
      enhances IL-1beta-induced MMP-9 secretion through the augmentation of ERK
      phosphorylation via AT1R in adult rat cardiac fibroblasts.

PMID- 20145377
TI  - Molecular analysis of antimicrobial resistance in gram-negative bacteria isolated
      from fish farms in Egypt.
AB  - As little is known about antimicrobial resistance genes in fish farms, this study
      was conducted to monitor the incidence and prevalence of a wide range of
      antimicrobial resistance genes in Gram-negative bacteria isolated from water
      samples taken from fish farms in the northern part of Egypt. Ninety-one out of
      two hundred seventy-four (33.2%) non-repetitive isolates of Gram-negative
      bacteria showed multidrug resistance phenotypes and harbored at least one
      antimicrobial resistance gene. PCR and DNA sequencing results showed that 72
      (26.3%) isolates contain tetracycline resistance genes and 19 (6.9%) isolates
      were positive for class 1 integrons with 12 different gene cassettes. The beta
      lactamase-encoding genes were identified in 14 (5.1%) isolates. The plasmid
      mediated quinolone resistance genes, qnr and aac(6')-Ib-cr, were identified in 16
      (5.8%) and 3 (1.1%) isolates, respectively. Finally, the florphenicol resistance
      gene, floR, was identified in four (1.5%) isolates. To the best of our knowledge,
      this is the first report for molecular characterization of antimicrobial
      resistance in Gram-negative bacteria isolated from fish farms in Africa.

PMID- 20145378
TI  - Application of gel permeation HPLC for lipoprotein profiling in dogs.
AB  - A high performance liquid chromatography system with a gel permeation column (GP
      HPLC) and an on-line dual enzymatic system was applied to lipoprotein analysis in
      dogs. A high density lipoprotein (HDL) fraction obtained by conventional
      ultracentrifugation gave a single peak at around 28-29 min. Similarly, a low
      density lipoprotein (LDL) fraction gave single peak at around 24-25 min. The
      lipoprotein profiles of healthy dogs were contained large HDL peaks and small LDL
      peaks, and VLDL and CM were only marginally detected. In diabetic dogs,
      concentrations of VLDL-triglyceride and VLDL-total-cholesterol were elevated
      significantly. The lipoprotein profile analysis by GP-HPLC method would be useful
      in explication of abnormality of lipid metabolism in dogs.

PMID- 20145379
TI  - The effect of feeding lactic acid to Salmonella typhimurium experimentally
      infected swine.
AB  - Antimicrobial resistant Salmonella are becoming more prevalent. Therefore,
      alternative methods to control swine Salmonella infection must be explored. We
      examined whether feeding lactic acid to swine is an effective way to control
      clinical and subclinical Salmonella Typhimurium infection in these animals. In
      this experiment, swine were inoculated with 5.6 x 10(7) CFU (hi-ST) or 5.6 x
      10(5) CFU (lo-ST) of S. Typhimurium per swine to reproduce clinical and
      subclinical infection. The swine were either fed a commercial feed supplemented
      with 2.8% lactic acid (LA) or the commercial feed without supplementation (C) to
      examine the effect of feeding lactic acid. Twenty 21 and 22 days old swine were
      divided into 4 groups, LA-hiST, C-hiST, LA-loST and C-loST, and fed the
      respective feed. They were inoculated S. Typhimurium at 51 and 52 days old.
      Clinical symptoms and the number of S. Typhimurium shed in feces were evaluated.
      The LA-hiST group did not show obvious clinical symptoms, such as diarrhea or
      febrile response, but the C-hiST group did show clinical symptoms. The number of
      S. Typhimurium shed in the feces of the LA-hiST group was lower than in that of
      the C-hiST group, and that of the LA-loST group was lower than that of the C-loST
      group. Our data suggest that dietary supplementation with 2.8% lactic acid can be
      an effective way to control clinical and subclinical infections of S. Typhimurium
      in swine.

PMID- 20145380
TI  - Plasma leptin concentration in dogs with diabetes mellitus.
AB  - The plasma leptin concentration was evaluated in dogs with diabetes mellitus.
      Twenty normal and sixteen diabetic dogs were divided into nonobese and obese
      groups based on body condition score, respectively. The obese normal dogs had
      significantly higher plasma leptin concentrations than the nonobese normal dogs,
      whereas there was no significant difference between the nonobese and obese
      diabetic dogs. In addition, the plasma leptin concentration in the obese diabetic
      dogs was significantly lower than that in the obese normal dogs. In conclusion,
      the plasma leptin concentrations in the diabetic dogs were affected by factors
      other than adiposity.

PMID- 20145381
TI  - Cutaneous Richter's syndrome, prognosis, and clinical, histological and
      immunohistological patterns: report of four cases and review of the literature.
AB  - BACKGROUND: Richter's syndrome (RS) corresponds to the transformation of chronic
      lymphocytic leukemia (CLL) into high-grade lymphoma. RS can involve extranodal
      sites including the gastrointestinal tract, lungs and skin. Cutaneous RS is rare,
      we describe 4 cases with clinical manifestations, histological and
      immunohistological patterns, and outcome. METHODS: Clinical data were analyzed
      and all patients' skin biopsy samples stained with HE for the CD20, CD5, CD3 and
      CD30 antigens. Epstein-Barr-virus (EBV)-encoded early RNA and clonal
      rearrangements were also analyzed. RESULTS: The patients' mean age at CLL
      diagnosis was 57 years (53-62 years), with a male/female sex ratio of 3:1. The
      transformation to cutaneous RS occurred between 8 and 75 months after initial
      diagnosis and progressed to a fatal systemic disease in 3 cases, between 24 and
      129 months. Cutaneous CLL was associated with earlier transformation in our
      series and could not be distinguished from RS on clinical grounds alone. All
      patients had a large-cell infiltrate and clonal rearrangements. CONCLUSIONS: The
      precise mechanism of RS is unclear, but a role of EBV has been suggested in
      fludarabine-treated CLL. For all our patients, the diagnosis of transformation
      was made on the basis of cutaneous localizations and led to intensified CLL
      treatment.

PMID- 20145382
TI  - Use of a tunnelled pleural catheter for the management of refractory hepatic
      hydrothorax: a new therapeutic option.
AB  - Refractory hepatic hydrothorax poses a challenging therapeutic dilemma, as
      treatment options are limited. Herein, we describe the case of a 48-year-old lady
      with advanced cirrhosis and recurrent transudative pleural effusion despite a
      sodium-restricted diet, optimal diuretic therapy and transjugular intrahepatic
      portosystemic shunt. Given the patient's platelet and coagulation disorders,
      thoracoscopic pleurodesis was deemed unsafe. Instead, a tunneled pleural catheter
      (PleurX(r)) was inserted under local anesthesia. Pleural drainage was achieved at
      the time of catheter placement and subsequently according to the patient's
      symptoms. Symptomatic improvement and gradual decrease of drainage volumes were
      noted. Six months following placement of PleurX, methicillin-resistant
      Staphylococcus aureus cellulitis at the insertion site prompted catheter removal.
      No pleural effusion was seen on chest X-ray at that time. Subsequent follow-up
      revealed spontaneous pleurodesis, as no recurrence of pleural effusion was seen
      over a 6-month follow-up period. Very few data are available with regard to the
      use of indwelling pleural catheters for benign transudative pleural effusion, and
      more specifically hepatic hydrothorax. Herein, we present this novel potential
      indication of the indwelling pleural catheter and illustrate the successful
      clinical outcome.

PMID- 20145383
TI  - Temperature-dependent sex determination and contemporary climate change.
AB  - Whether species that have persisted throughout historic climatic upheavals will
      survive contemporary climate change will depend on their ecological and
      physiological traits, their evolutionary potential, and potentially upon the
      resources that humans commit to prevent their extinction. For those species where
      temperatures influence sex determination, rapid global warming poses a unique
      risk of skewed sex ratios and demographic collapse. Here we review the specific
      mechanisms by which reptiles with temperature-dependent sex determination (TSD)
      may be imperilled at current rates of warming, and discuss the evidence for and
      against adaptation via behavioural or physiological means. We propose a scheme
      for ranking reptiles with TSD according to their vulnerability to rapid global
      warming, but note that critical data on the lability of the sex determining
      mechanism and on the heritability of behavioural and threshold traits are
      unavailable for most species. Nevertheless, we recommend a precautionary approach
      to management of reptiles identified as being at relatively high risk. In such
      cases, management should aim to neutralise directional sex ratio biases (e.g. by
      manipulating incubation temperatures or assisted migration) and promote adaptive
      processes, possibly by genetic supplementation of populations. These practices
      should aid species' persistence and buy time for research directed at more
      accurate prediction of species' vulnerability.

PMID- 20145385
TI  - 'Pure' partial trisomy 4q26-->q35.2 resulting from a familial unbalanced
      translocation t(4;10)(q26;q26.3).
AB  - A 3-year-old girl with an inherited translocation of 4q onto the long arm of
      chromosome 10 is reported as a case of 'pure' partial trisomy 4q. The main
      clinical features of the patient included moderate mental retardation (IQ = 40),
      growth retardation, language handicap, right hand preaxial hexadactyly, and
      abnormal electroencephalogram. Conventional cytogenetic analysis showed partial
      trisomy 4q25-->qter was present in the patient, both patient's father and
      grandmother were apparently balanced translocation t(4;10) (q25;q26) carriers,
      which suggests that the partial trisomy 4q25-->qter in the patient results from
      unbalanced segregation of the father's translocation. The extension of the
      trisomic 4q region was redefined by array comparative genomic hybridization
      (array-CGH), the breakpoint on chromosome 4 was located at 4q26 (between
      115,596,658 bp and 118,785,802 bp from the telomere of 4p), and an approximately
      0.54-Mb microdeletion del(10)(q26.3) (between 134,750,859 bp and 135,286,223 bp
      from the telomere of 10p) was identified. FISH and RT-qPCR confirmed that
      del(10)(q26.3) was also present in both father and grandmother, which suggests
      that their translocations are actually unbalanced and the patient's abnormal
      phenotypes may only ascribe to partial trisomy 4q26-->q35.2.

PMID- 20145384
TI  - Molecular mechanisms of sex determination in reptiles.
AB  - Charles Darwin first provided a lucid explanation of how gender differences
      evolve nearly 140 years ago. Yet, a disconnect remains between his theory of
      sexual selection and the mechanisms that underlie the development of males and
      females. In particular, comparisons between representatives of different phyla
      (i.e., flies and mice) reveal distinct genetic mechanisms for sexual
      differentiation. Such differences are hard to comprehend unless we study
      organisms that bridge the phylogenetic gap. Analysis of variation within
      monophyletic groups (i.e., amniotes) is just as important if we hope to elucidate
      the evolution of mechanisms underlying sexual differentiation. Here we review the
      molecular, cellular, morphological, and physiological changes associated with sex
      determination in reptiles. Most research on the molecular biology of sex
      determination in reptiles describes expression patterns for orthologs of
      mammalian sex-determining genes. Many of these genes have evolutionarily
      conserved expression profiles (i.e., DMRT1 and SOX9 are expressed at a higher
      level in developing testes vs. developing ovaries in all species), which suggests
      functional conservation. However, expression profiling alone does not test gene
      function and will not identify novel sex-determining genes or gene interactions.
      For that reason, we provide a prospectus on various techniques that promise to
      reveal new sex-determining genes and regulatory interactions among these genes.
      We offer specific examples of novel candidate genes and a new signaling pathway
      in support of these techniques.

PMID- 20145386
TI  - Sinusoidal heart rate patterns as a manifestation of massive fetomaternal
      hemorrhage in a monochorionic-diamniotic twin pregnancy: a case report.
AB  - OBJECTIVE: A case of fetomaternal hemorrhage (FMH) in monochorionic twins is
      reported. METHOD: Case report. RESULT: The patient felt a decrease in fetal
      movements at 32 gestational weeks. Cardiotocography showed sinusoidal heart rate
      patterns in both fetuses. The fetal hemoglobin level in maternal blood was 6.6%
      (normal 0.0-1.0%). Since the patient was diagnosed with massive FMH, cesarean
      section was performed and both babies delivered to receive neonatal treatment.
      Severe anemia was apparent in both infants, based on red blood cell count,
      hemoglobin concentration, and hematocrit of 86 x 10 and 85 x 10(4)/mm(3) (normal
      376-456 x 10(4)/mm(3)), 3.1 g/dl each (normal 10.9-13.5 g/dl), and 10.7 and 10.4%
      (normal 32.2-41.2%), respectively. Severe anemia may develop in both fetuses
      following massive FMH in monochorionic twins. As such, if abnormal circulation is
      detected in 1 monochorionic twin, the other fetus will also require special
      attention.

PMID- 20145387
TI  - Association of antigen-stimulated release of tumor necrosis factor-alpha in whole
      blood with response to chemotherapy in patients with pulmonary multidrug
      resistant tuberculosis.
AB  - BACKGROUND: We have previously reported that TNF-alpha levels correlate to total
      mycobacterial burden in tuberculosis (TB) patients. OBJECTIVE: To characterize
      the dynamics of cytokine responses in TB patients during chemotherapy to identify
      potential surrogate markers for effective treatment. METHODS: Following induction
      by culture filtrate proteins in whole blood, production patterns of TNF-alpha, IL
      10, IFN-gamma and IL-12 were measured in 23 non-multidrug-resistant (MDR)-TB and
      16 MDR-TB patients and in 31 healthy controls. Rates of mycobacterial clearance
      from the sputum were then measured and compared. RESULTS: Prior to the initiation
      of chemotherapy, TNF-alpha and IL-10 levels were significantly higher in TB
      patients than in healthy controls while IFN-gamma and IL-12 levels were similar.
      During chemotherapy, the levels of all 4 cytokines increased. We evaluated these
      responses separately in patients that did and did not clear their sputum culture
      at 2 and 6 months. At 2 months, decreases in both IFN-gamma and IL-12 correlated
      strongly with a successful early response, while after 6 months of therapy, when
      half (7/14) of MDR-TB patients were still sputum culture positive, downregulation
      of TNF-alpha was uniquely correlated with sputum conversion between the groups.
      CONCLUSION: Our findings suggest the possibility that the regulation of TNF-alpha
      production in whole blood may be a more specific indicator of sputum conversion
      at 6 months than IFN-gamma, IL-12 or IL-10 in MDR-TB patients.

PMID- 20145388
TI  - Rapid anaemia control with epoetin: results of a Swiss survey on treatment of
      chemotherapy-induced anaemia.

PMID- 20145389
TI  - Macronutrient intake and metabolic syndrome in subjects at high cardiovascular
      risk.
AB  - BACKGROUND: The effect of macronutrient intake on the metabolic syndrome (MS) is
      still controversial. Our aim in this study was to assess the relationships
      between macronutrient intake and the risk of developing the MS in subjects at
      high cardiovascular risk. METHODS: In this cross-sectional study, 967 high-risk
      men and women (55-80 years) were assessed according to the MS criteria defined by
      the National Cholesterol Education Program Adult Treatment Panel III (ATP3) and
      those established by the International Diabetes Federation (IDF). A 137-item
      validated food frequency questionnaire was used. Odds ratios (OR) for
      macronutrient intake and MS were calculated and adjustments were made for
      potential confounders. RESULTS: When applying the ATP3 criteria, an inverse
      association was found for fiber and polyunsaturated fatty acid (PUFAs) intake,
      with ORs of 0.55 (95% CI: 0.35-0.86) and 0.60 (95% CI: 0.39-0.94), respectively,
      for the 5th versus the 1st quintile. Using the IDF criteria, an inverse
      association between fiber intake and the MS was obtained whereas a direct
      association was found between carbohydrate intake and the MS: OR = 1.71 (95% CI:
      1.05-2.79) for the highest versus the lowest quintile. CONCLUSIONS: A diet rich
      in fiber and PUFAs is correlated with a reduced risk of MS in subjects at high
      cardiovascular risk.

PMID- 20145391
TI  - Variation in the C-reactive protein gene is associated with serum levels of CRP
      in patients with acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Elevated levels of C-reactive protein (CRP) are found in
      up to three quarters of patients with acute ischemic stroke and are associated
      with poor outcome. We investigated whether haplotypes representing common
      variations in the CRP gene are associated with levels of CRP in patients with
      acute ischemic stroke. METHODS: We included 185 patients with ischemic stroke in
      whom CRP was measured within 24 h of symptom onset. Common haplotypes within the
      CRP gene were determined by 3 genotype-tagging single-nucleotide polymorphisms
      (SNPs). RESULTS: Four haplotypes with frequencies >5% covered 99.2% of the
      genetic variation. Haplotype 4 (CCG, frequency 8.3%) was associated with a 20.6
      mg/l (95% CI, 9.8-30.4) stronger increase in CRP level as compared with haplotype
      1 (CTC, frequency 33.7%). CONCLUSION: Variation in the CRP gene is associated
      with levels of CRP in acute ischemic stroke.

PMID- 20145392
TI  - One-year case fatality and disability after posterior circulation infarction in a
      Chinese hospital-based stroke study.
AB  - BACKGROUND AND PURPOSE: Controversy exists as to whether posterior circulation
      infarction (PCI) has a poorer outcome compared to anterior circulation infarction
      (ACI). We aimed to investigate whether PCI had different clinical outcomes from
      ACI in Chinese patients with ischemic stroke. METHODS: Data on ischemic stroke
      patients with ACI or PCI were collected including demographics, risk factors and
      1-month, 3-month, and 1-year case fatality and disability (defined as modified
      Rankin Scale 3-5). Multivariate regression models were used to analyze predictors
      for death and disability. RESULTS: Of the 1,962 enrolled cases, 433 (22.1%) had
      PCI. The case fatality of PCI at 1-month, 3-month and 1-year follow-up (FU) were
      lower than that of ACI (3.93, 5.3 and 9.7% vs. 7.26, 9.3 and 13.7%, p <0.05), and
      the proportion of disability was also lower in PCI at 3-month FU (19.6 vs. 29.1%,
      p<0.001) and 1-year FU (6.5 vs. 15.2%, p<0.001). The adjusted hazard ratio of
      death for PCI was 0.52 at 1 month (95% CI 0.29-0.94) and 0.52 at 3 months (95% CI
      0.31-0.85), and the adjusted odds of disability in patients with PCI was 0.53 at
      1 year (95% CI 0.35-0.81). CONCLUSIONS: In our cohort, patients with PCI have a
      lower risk of death at 1- and 3-month FU and a lower proportion of disability at
      1-year FU, which needs to be verified by future studies.

PMID- 20145393
TI  - Stewart-Treves syndrome: questionable response to weekly paclitaxel.

PMID- 20145394
TI  - Interstitial pneumonitis after treatment with bevacizumab and pegylated liposomal
      doxorubicin in a patient with metastatic breast cancer.

PMID- 20145390
TI  - Factors affecting health-related quality of life assessed with the SF-36v2 health
      survey in outpatients with chronic-stage ischemic stroke in Japan--cross
      sectional analysis of the OASIS study.
AB  - BACKGROUND AND PURPOSE: The number of chronic-stage ischemic stroke patients in
      Japan continues to increase, because of decreasing mortality. This study was
      designed to ascertain health-related quality of life (HRQOL) in ischemic stroke
      patients and to analyze in detail factors affecting HRQOL. METHODS: 2,069
      outpatients (1,226 males, 843 females; mean age: 71 years; median duration after
      onset: 20.5 months) with chronic-stage ischemic stroke visiting 150 institutions
      in Japan were enrolled. HRQOL was evaluated using the second version of the
      patient self-administered Medical Outcome Study 36-Item Short-Form Health Survey
      (SF-36v2) questionnaire. RESULTS: All 8 domain scores and the physical component
      summary (PCS) score of SF-36v2 in stroke patients were significantly lower than
      those of Japanese national norms (JNN). The PCS score (36.6 +/- 16.1) and mental
      component summary (MCS) score (50.0 +/- 10.2) were lower than those of age
      matched JNN (p < 0.001). Age, modified Rankin Scale (mRS), duration after onset
      and Japan Stroke Scale Depression score (JSS-D) were significantly correlated
      with PCS, as were role limitation because of physical problem, bodily pain,
      vitality and role limitation because of emotional problem scores; duration after
      onset and JSS-D were significantly correlated with MCS. Negative factors for PCS
      were older age, higher mRS, presence of subjective symptoms, neurological signs,
      rehabilitation and concomitant antidepressants. Negative factors for MCS were
      presence of subjective symptoms, psychiatric signs and concomitant
      antidepressants. CONCLUSIONS: HRQOL scores in ischemic stroke patients (chronic
      stage) are significantly correlated with not only age, mRS, duration after onset
      and JSS-D, but also presence of subjective symptoms and neurological/psychiatric
      signs, which could be targets for treatment.

PMID- 20145395
TI  - Stem cell engineering for cardiac tissue regeneration.

PMID- 20145396
TI  - Injectable hydrogel helps bone marrow-derived mononuclear cells restore infarcted
      myocardium.
AB  - BACKGROUNDS: Experimental and clinical studies have suggested that cell
      implantation could improve cardiac function after myocardial infarction (MI).
      However, this technique was limited by decreased engraftment and survival of
      transplanted cells within the ischemic tissue. The present study was performed to
      investigate whether implantation of bone marrow-derived mononuclear cells
      (BMMNCs) encapsulated in hydrogel could increase cell engraftment and help to
      restore cardiac function of MI rabbits. METHODS: MI was induced in rabbits by
      coronary artery ligation. One week later, cell culture medium, Dex-PCL
      HEMA/PNIPAAm hydrogel, BMMNCs in medium or BMMNCs in hydrogel were injected into
      the infarcted area of the left ventricle (LV). RESULTS: Increased cell
      engraftment was observed 48 h after injection when cells were encapsulated in
      hydrogel; 30 days after treatment, echocardiographic studies showed that
      injection of BMMNCs in hydrogel preserved LV ejection fraction and attenuated LV
      dilatation compared with other groups. Histological analysis indicated that
      injection of BMMNCs in hydrogel enhanced neovascular formation and prevented scar
      expansion compared with the other groups. CONCLUSION: Injection of hydrogel
      encapsulated BMMNCs increased cell engraftment and improved LV function; this
      technique may serve as an effective approach to restore infarcted myocardium.

PMID- 20145397
TI  - Preventive effect of commercial desensitizing toothpastes on bovine enamel
      erosion in vitro.
AB  - This study evaluated in vitro commercial desensitizing toothpastes with respect
      to the prevention of erosion and explored the effect of their agents alone or in
      combination with fluoride. Bovine enamel blocks were randomly allocated to five
      groups of 20 and exposed to: Sensodyne ProNamel (1,425 ppm F as NaF, 5% KNO(3)),
      Sensodyne Original (no fluoride, 10% SrCl(2)), Colgate Sensitive (1,450 ppm F as
      sodium monofluorophosphate, 5% K citrate), Crest (fluoride-only toothpaste, 1,100
      ppm F as NaF) and water (negative control). A second experiment was conducted
      with experimental dentifrices containing fluoride (NaF, 1,100 ppm F), 10%
      SrCl(2), 5% KNO(3 )or 5% K citrate alone or the latter three combined with F. The
      samples were submitted to four cycles, alternating demineralization (cola, 10
      min) and remineralization (artificial saliva, 1 h). Before and between cyclic de-
      and remineralization, blocks were treated with slurries of the respective
      toothpastes or water (1 min). Erosive tissue loss was analyzed by profilometry.
      Data were analyzed by Kruskal-Wallis and Dunn's tests (p < 0.05). The mean
      erosion depth (+/- SE, mum) was significantly less for Colgate Sensitive (0.04 +/
      0.00), Sensodyne Original (0.06 +/- 0.01) and Crest (0.07 +/- 0.01) than for
      Sensodyne ProNamel (2.36 +/- 0.25) or water (2.92 +/- 0.24), which did not
      significantly differ from each other. Both F and the desensitizing agents alone
      reduced erosion, but no additive effect was found. In addition, the combination
      of F and KNO(3) did not reduce erosion. These in vitro results suggest that the
      presence of fluoride or desensitizing substances in toothpastes, alone or in
      combination, can reduce erosion of enamel, but this is not valid for all the
      formulations.

PMID- 20145398
TI  - A computer model of dementia prevalence in Australia: foreseeing outcomes of
      delaying dementia onset, slowing disease progression, and eradicating dementia
      types.
AB  - BACKGROUND: A computer model was designed to test hypothetical scenarios
      regarding dementia prevalence in Australia (2001-2040). METHODS: The study
      implemented 3 scenarios: delaying dementia onset, slowing disease progression
      and, in a previously unpublished experiment, eradicating dementia types.
      Sensitivity analysis and parameter variation were the main methods of
      experimentation. RESULTS: The model predicts that delaying dementia onset by 5
      years will reduce the 2040 prevalence by 37%. An onset delay of 2 years,
      introduced in 2010, will reduce the 2040 prevalence by 16%. Slowing disease
      progression increases the 2040 prevalence by 4-7%. Total eradication of
      Alzheimer's disease (currently approximately 50% of all dementia cases) in 2020
      will decrease the 2040 prevalence by 42%. CONCLUSION: Computer modeling of future
      scenarios and interventions helps health and aged care planners understand the
      likely challenges society will face with the ageing of the world's population.

PMID- 20145399
TI  - Ethnic variations in dementia: the contributions of cardiovascular, psychosocial
      and neuropsychological factors.
AB  - BACKGROUND: Ethnic variations in dementia rate have been reported worldwide.
      Understanding these differences is vital for aetiological research, clinical care
      and health service planning. While age and gender have been consistently
      implicated, the reasons behind interethnic variation remain unclear. METHOD: We
      used data from the Singapore National Mental Health Survey (Elderly) in 2003, a
      cross-sectional population-based study to investigate the extent to which
      differences in cardiovascular risk factors, psychosocial factors and cognitive
      functional status contributed to ethnic differences in dementia prevalence among
      Chinese, Malays and Indians. RESULTS: Ethnic differences in dementia prevalence
      (4.2% in Chinese, 9.4% in Malays and 8.8% in Indians) were not explained by
      differences in gender, age and education (Malays vs. Chinese: adjusted OR = 3.11;
      Indians vs. Chinese: OR = 4.30). Differences in cardiovascular factors,
      depression or leisure time activities contributed modestly to the differences,
      but the OR remained significantly elevated. Differences in Mini-Mental State
      Examination scores contributed the most to explaining the ethnic differences
      (Malays vs. Chinese: adjusted OR = 0.73; Indians vs. Chinese: OR = 1.18).
      CONCLUSION: Cognitive functional reserve accounted for much of the ethnic
      differences in dementia prevalence and its assessment has implications for the
      detection and treatment of dementia in multiethnic populations.

PMID- 20145400
TI  - Attention network functioning in patients with dementia with Lewy bodies and
      Alzheimer's disease.
AB  - BACKGROUND: Attention deficits are at the core of the defects in
      neuropsychological performance which define both dementia with Lewy bodies (DLB)
      and Alzheimer's disease (AD). Most studies have used separate tasks to test
      different attention abilities in patients with these diagnoses, precluding the
      assessment of any interaction among the different attention components. METHODS:
      We used a version of the Attention Network Test in which the alerting, orienting
      and executive attention networks, along with their interactions, could be
      assessed with a single task. Three groups of participants were tested: DLB
      patients (n = 13), AD patients (n = 18) and healthy controls (n = 18). RESULTS:
      The alerting signal improved orienting attention and increased the conflict
      effect in the healthy controls, but they had no effect on these networks in the
      AD patients. The DLB patients only showed preserved orienting and conflict
      effects when the alerting signal was present, indicating that there was
      regulation of the orienting and executive attention networks by the alerting
      signal. CONCLUSIONS: The most important differences among the 3 groups were
      observed in the attention network interactions, where alerting played a more
      relevant role in the DLB than in the AD patients. Under alerting states, the DLB
      patients showed evidence of certain regulation in the orienting and executive
      attention networks.

PMID- 20145401
TI  - Depression in pancreatic cancer: sense of impending doom.

PMID- 20145402
TI  - Investigation of the incidence of pancreatic cancer-related depression and its
      relationship with the quality of life of patients.
AB  - AIM: To investigate the incidence of pancreatic cancer-related depression and the
      relationship between symptoms of depression and the quality of life (QoL) of
      patients. METHODS: 262 inpatients with cancer of the digestive system (pancreatic
      cancer, liver cancer, esophageal cancer, gastric cancer, and colorectal cancer)
      from four Guangzhou hospitals were enrolled into the study between June 2007 and
      June 2009. The Hamilton Rating Scale for Depression-24 questionnaire was used to
      assess the degree of depression. QoL of all patients was evaluated by EORTC QLQ
      C30. Additionally, EORTC QLQ-PAN-26 was used for patients with pancreatic cancer.
      RESULTS: The incidence of depression among pancreatic cancer patients was
      significantly higher than among other digestive cancers. More pancreatic cancer
      patients suffered severe depression than those with liver cancer and gastric
      cancer. Compared with other groups with depression, QoL of pancreatic cancer
      patients in each functioning scale was significantly worse, while the symptoms of
      fatigue and pain were significantly severe. QoL of pancreatic cancer patients
      with depression in role, emotional, and social functioning were sharply poorer
      than those without depression. The symptoms of fatigue, pain and appetite loss in
      cancer patients with depression were significantly more frequent than those
      without depression. CONCLUSION: Compared with other cancers of the digestive
      system, depressive symptoms are common psychological disturbances in pancreatic
      cancer patients. Moreover, depression significantly lowers QoL in pancreatic
      cancer patients.

PMID- 20145403
TI  - Relationship between Helicobacter pylori tyrosine-phosphorylated CagA-related
      markers and the development of diffuse-type gastric cancers: a case-control
      study.
AB  - BACKGROUND/AIMS: Tyrosine phosphorylation of the EPIYA motif in Helicobacter
      pylori CagA (CagA-P) plays an important role in toxic reaction. Diffuse-type
      gastric cancer (DGC) has a poor prognosis. We tried to clarify the expression
      level of CagA-P in DGC patients. METHODS: We enrolled 42 early-stage DGC patients
      (DGC group; 20 males, 22 females, mean age 58.2 years) and 42 age- and gender
      matched atrophic gastritis (AG) patients (AG group) as controls. We evaluated
      histological and serological gastritis and examined two markers; the serum titer
      of anti-CagA-P antibody and CagA-P expression in gastric mucosa. RESULTS: In the
      DGC group, we found significantly higher corpus histological gastritis scores for
      activity, atrophy, and intestinal metaplasia. The titer of anti-CagA-P antibody
      and CagA-P expression in the corpus were significantly higher in the DGC group,
      especially in females (p < 0.05). Sixteen patients (38.1%) in the DGC group
      showed both positive markers, and the odds ratio for DGC occurrence was 4.00 (95%
      CI = 1.07-14.91), while that for females was 9.00 (95% CI = 1.29-62.97).
      CONCLUSIONS: CagA-P plays a role in active corpus gastritis, which may link to
      DGC carcinogenesis. Clinical quantification of CagA-P-related markers may be
      useful for the evaluation of DGC risk, especially in females.

PMID- 20145404
TI  - Intestinal protozoa infections among patients with ulcerative colitis: prevalence
      and impact on clinical disease course.
AB  - BACKGROUND: Epidemiological and microbiologic studies suggest that
      enteropathogenic microorganisms play a substantial role in the clinical
      initiation and relapses of inflammatory bowel disease. AIM: To explore the
      prevalence of intestinal protozoa in patients with ulcerative colitis (UC) and
      its impact on clinical disease course. METHODS: A total of 215 patients with
      definitive diagnosis of UC were studied. Fresh feces samples taken from all UC
      patients were examined immediately using trichrome-staining methods. RESULTS: A
      total of 103 female and 112 male UC patients were analyzed. The mean age at
      diagnosis was 30.5 +/- 10.8 years. The prevalence of overall parasitic infections
      was 24% and distributed as follows: Blastocystis hominis in 22 patients (10%),
      Endolimax nana in 19 cases (9%), and Entamoebahistolytica in 11 cases (5%). A
      significantly increased frequency of protozoa infection was found in those
      patients with persistent activity and intermittent activity as compared to active
      than inactive group (p = 1 x 10(-7), OR 13.05, 95% CI 4.28-42.56, and p = 0.003,
      OR 1.42-14.47, respectively). Interestingly, this association remained
      significant when we compared the persistent activity group versus intermittent
      activity group (p = 0.003, OR 2.97, 95% CI 1.35-6.59). Subgroup analysis showed
      no association between protozoa infection (E. histolytica, B. hominis, and E.
      nana) and other clinical variables such as gender, extent of disease,
      extraintestinal complications, medical treatment and grade of disease activity.
      CONCLUSION: The prevalence of intestinal protozoa infections in Mexican UC
      patients was 24% and these microorganisms could be a contributing cause of
      persistent activity despite medical treatment in our population.

PMID- 20145405
TI  - Transpontine connection fibers between corticospinal tracts in hemiparetic
      patients with intracerebral hemorrhage.
AB  - OBJECTIVES: A connection of fibers between corticospinal tracts (CSTs) at the
      pons, originating from the CST of the affected hemisphere, has been observed in
      hemiparetic patients with stroke. The authors investigated the incidence and the
      clinical significance of transpontine connection of fibers (TCFs) in hemiparetic
      patients with intracerebral hemorrhage (ICH), using diffusion tensor tractography
      (DTT). SUBJECTS AND METHODS: Forty-two patients with ICH with weakness of the
      affected extremities at the time of DTI scanning and 41 age-matched control
      subjects were recruited. TCFs were classified into three types according to
      severity: type A - no TCF extending to the opposite hemisphere, type B - a TCF
      crossing to the opposite hemisphere and ending at the subcortical level, and type
      C - a TCF crossing the pons and ascending to the cortex of the opposite
      hemisphere. RESULTS: TCFs originating from the CST in affected and unaffected
      hemispheres were significantly more prevalent among patients than controls (both
      p < 0.05). In addition, TCF severity was found to be closely related to motor
      function reduction in affected extremities (p < 0.05) and to extent of CST injury
      in affected hemispheres (p < 0.05). CONCLUSIONS: TCF appears to represent a
      compensatory mechanism associated with motor weakness or CST injury in patients
      with ICH.

PMID- 20145406
TI  - Impact of surgical severity and analgesic treatment on plasma corticosterone in
      rats during surgery.
AB  - Tissue injury and anaesthesia during surgery induce a stress response associated
      with increased glucocorticoid secretion from the adrenal glands. This response
      alters the normal physiology and may cause postoperative morbidity, as well as
      affect the results during acute experiments. The aim of the present investigation
      was to study the effect of surgical severity and analgesic treatment on
      circulating corticosterone in male Sprague-Dawley rats. Male rats were treated
      with either lidocaine infiltrated during surgery, buprenorphine (0.05 or 0.1
      mg/kg subcutaneously) or saline subcutaneously. Each treatment group was
      subjected to either arterial catheterisation or arterial catheterisation and
      laparotomy. A catheter was inserted in the common carotid artery and blood was
      collected during surgery and during anaesthesia 6 h after surgery. Lidocaine
      treatment reduced the corticosterone levels compared to saline treatment after
      catheterisation but not after laparotomy. Buprenorphine treatment reduced the
      corticosterone levels during the first hour after surgery after both
      catheterisation and laparotomy. The higher buprenorphine dose led to an earlier
      and more pronounced reduction, especially after laparotomy. In the present study,
      the corticosterone response during surgery in laboratory rats is correlated with
      the severity of the procedure, and buprenorphine reduces the surgical stress
      response more effectively than lidocaine treatment.

PMID- 20145407
TI  - Allergy or tolerance, that's the question.

PMID- 20145408
TI  - Distribution of core fragments from the major cat allergen Fel d 1 is maintained
      among the main anatomical sites of production.
AB  - BACKGROUND: Polymorphism of Fel d 1 has long been observed, but structural
      characterization of Fel d 1 variants among the various sites of production and
      animals is still missing. This study was aimed at elucidating the structural
      polymorphism of this protein as a function of the site of production and the
      resulting influence on the immunological behavior of the allergen. METHODS: Fel d
      1 was water-extracted from the 4 main sites of production, i.e. cheek zone,
      interdigital zone, anal sac (AS), and chest area and a panel of 10 cats. Fel d 1
      like materials were immunoblotted, immunopurified and characterized by MALDI-TOF
      MS. Immunoreactivity was studied using ELISA dose-dependent curves at
      equilibrium. RESULTS: In all areas, 4-10 isoforms ranging from 7 to 40 kDa were
      detected by MS. Essentially two truncated heterodimers of 13-14 and 16-17 kDa
      were identified together with intact Fel d 1 in all compartments and they were
      largely predominant in AS. These core fragments were found to contribute to a
      variable recognition by antibodies in a panel of ELISA. CONCLUSIONS: Our study
      identified truncated dimers of Fel d 1, probably resulting from proteolytic
      degradation of both chains and present in all cats. Core fragments are largely
      distributed among anatomical sites of production and especially well represented
      in AS. They are recognized as intact allergens by antibodies and may therefore
      introduce discrepancies in allergen measurement depending on the variable amount
      of intact and degraded Fel d 1 produced by the cat.

PMID- 20145409
TI  - Molecular cloning and immunochemical characterization of a novel major Japanese
      cedar pollen allergen belonging to the aspartic protease family.
AB  - BACKGROUND: Japanese cedar (Cryptomeria japonica) pollen is a major cause of
      seasonal pollinosis in Japan. Protease activity in the pollen grains may trigger
      pro-allergic responses but no such proteases have yet been identified as pollen
      allergens. OBJECTIVES: We report the molecular cloning and immunochemical
      characterization of a novel C. japonica pollen allergen belonging to the aspartic
      protease family. METHODS: We focused on the C. japonica pollen allergen spot No.
      63 (CPA63, 47.5% IgE binding frequency) on our 2-dimensional IgE immunoblot map.
      The internal amino acid sequences were determined using time-of-flight mass
      spectrometry. Full-length cpa63 cDNA was cloned by rapid amplification of cDNA
      ends (RACE)-PCR. Recombinant CPA63 (r-CPA63) was expressed using the baculovirus
      insect cell culture system and its IgE binding capacity was analyzed by enzyme
      linked immunosorbent assay (ELISA). The proteolytic activity of r-CPA63 was also
      assessed using a putative mature enzyme produced upon autolysis. RESULTS: cpa63
      cDNA encoded a 472 amino acid polypeptide showing about 40% sequence identity to
      members of the plant atypical aspartic protease family. ELISA showed that r-CPA63
      was recognized by IgE antibodies in the serum of 58% (18/31) of Japanese cedar
      pollinosis patients. We also demonstrated an aspartic protease-like enzyme
      activity of the putative mature r-CPA63. CONCLUSIONS: We have identified the
      first plant aspartic protease allergen from Japanese cedar pollen. The
      availability of the CPA63 sequence and its recombinant allergen production system
      are useful not only for pharmaceutical applications but also for further
      examination of the role of protease activity in the pathogenesis of cedar
      pollinosis.

PMID- 20145410
TI  - Long-term characteristics of hazelnut allergy in an adjuvant-free mouse model.
AB  - BACKGROUND: Clinically it is recognized that tree nut allergies such as hazelnut
      allergy are not usually outgrown. Specific mechanisms underlying the persistence
      of such food allergies are incompletely understood. Here we studied the natural
      history and the long-term immune and clinical characteristics of hazelnut allergy
      in an adjuvant-free mouse model. METHODS: BALB/c mice were sensitized to hazelnut
      protein using a transdermal sensitization protocol that does not use adjuvant.
      After establishing sensitization, exposure to hazelnut was withdrawn for 3, 5 or
      8 months. The fate of circulating IgE antibodies was monitored. Subsequently,
      mice were given booster exposures and examined for memory IgE antibody and spleen
      cell IL-4 responses. Clinical characteristics and hypothermia responses upon oral
      allergen challenge were studied. RESULTS: Upon allergen withdrawal, circulating
      hazelnut-specific IgE antibody levels began to drop. Nevertheless, IgE responses
      once established remained at significantly high levels for up to 8 months (the
      last time point studied) despite withdrawal of allergen exposure. Memory IgE
      responses to booster exposures were robust after 3, 5 or 8 months of allergen
      withdrawal. Furthermore, significant clinical reactivity to oral hazelnut
      challenge, and hypothermia responses were demonstrable at each of these time
      points. Long-lasting spleen cell memory IL-4 responses to hazelnut were
      detectable in these mice explaining the mechanism of sustenance of IgE responses
      and clinical sensitization. CONCLUSIONS: Hazelnut allergy once established
      persists for long periods, despite withdrawal of allergen exposure, due to long
      lasting, memory IgE and IL-4 responses.

PMID- 20145411
TI  - Gene expression profiles in fetal and neonatal rat offspring of energy-restricted
      dams.
AB  - BACKGROUND/AIMS: Nutrition during fetal and early postnatal development can have
      permanent effects on physiology resulting in an increased risk for disease in
      later life. The aim of this study was to explore changes in gene expression
      related to maternal energy restriction during pregnancy in rat fetuses and in
      neonatal rat offspring. METHODS: From day 4 of gestation until parturition,
      energy-restricted dams received either 75 or 50% of ad libitum food intake.
      Microarray analyses were performed on whole 13- and 17-day fetuses and 1-day-old
      pups. Protein and fat contents of the dams' milk were analyzed in the different
      feeding groups. RESULTS: A surprisingly small number of genes were differentially
      expressed between the groups, probably due to the strict control of fetal
      development. Interestingly, the expressions of many pancreatic digestion enzymes
      were reduced in the 1-day-old pups of the energy-restricted dams. A statistically
      significant difference in milk protein content was observed on day 1 post-partum
      between the gestationally food-restricted groups. CONCLUSIONS: The expressions of
      several genes that may have an important role in the normal development of organs
      were affected by undernutrition during fetal development. In addition,
      undernutrition may have affected the function of the exocrine pancreas.

PMID- 20145412
TI  - Nutrition tailored to the individual? Not just yet - realigning nutrigenomic
      science with contemporary society.
AB  - About a decade ago, scientists and science journalists presented nutrigenomics as
      a grand promise that each of us would soon know which foods fit in our personal
      healthy diet. Meanwhile, expectations have been adjusted to fit a changed
      reality. Simultaneously, societal issues surrounding personalized nutrition
      continue to rise, including whether consumers need it, food industry can produce
      it, all relevant stakeholders are willing and able to work together, and if it is
      a desirable way to go for nutrition. The commentary below reports the main
      results of 6 research projects that focused on nutrigenomics and its role in
      society.

PMID- 20145413
TI  - Activation of GRP78 on endothelial cell membranes by an ADAM15-derived peptide
      induces angiogenesis.
AB  - Impaired angiogenesis is one of the features of ischemic diseases. We have
      previously identified, by screening a phage display peptide library, a peptide
      that induces angiogenesis in endothelial cells under hypoxic conditions by
      binding the cell's membrane heat shock protein GRP78. Protein data base search
      identified 4 amino acids (HWRR) of that synthetic peptide present on the ADAM15
      metalloprotease domain, a protein considered to be involved in
      neovascularization. Three peptides were synthesized according to the ADAM15
      sequence placing HWRR at different positions. Peptide ADoPep1 exhibited
      significant angiogenic properties under hypoxic conditions as determined by cell
      proliferation, migration and tube formation. In a mouse hind limb ischemia model,
      a single injection of the peptide restored blood perfusion. The identified
      peptide was found to activate GRP78 on endothelial cell membrane and siRNA
      directed against the GRP78 mRNA interfered with induction of angiogenesis by the
      peptide. The peptide binding induced a decrease in heat shock protein GRP78 that
      is overexpressed under hypoxic conditions. The mechanism of peptide-induced
      angiogenic activity involves inhibition of apoptosis as well as increased Akt
      phosphorylation and ERK 1/2 activation. The peptide did not induce VEGF receptor
      2 protein synthesis and phosphorylation, suggesting a VEGF-independent mechanism
      of angiogenesis.

PMID- 20145414
TI  - Insulin inhibits and oral sucrose increases neointimal growth after arterial
      injury in rats.
AB  - BACKGROUND/AIMS: In our previous studies, rats on insulin treatment (5 U/day) and
      oral glucose to avoid hypoglycemia had reduced neointimal growth after arterial
      injury. However, plasma glucose in the insulin-treated rats was lower than normal
      and the effect of oral glucose remained undetermined. In this study, the effects
      of normoglycemic hyperinsulinemia and oral glucose or sucrose were investigated
      in the same model. METHODS: Rats were divided into 6 groups: (1) control implants
      and tap water; (2) insulin implants (5 U/day) and oral glucose + i.p. glucose to
      avoid any glucose lowering; (3) insulin implants (4 U/day) and oral glucose; (4)
      insulin implants (4 U/day) and oral sucrose; (5) control implants and oral
      glucose, and (6) control implants and oral sucrose. RESULTS: Insulin treatment at
      both doses reduced neointimal area (p < 0.001) 14 days after injury in rats
      receiving oral glucose but not in those receiving oral sucrose. Oral glucose,
      without insulin, had no effect on neointimal formation, whereas oral sucrose
      increased neointimal growth (p < 0.05). Oral sucrose (p < 0.05) but not oral
      glucose decreased insulin sensitivity measured with hyperinsulinemic clamps.
      CONCLUSIONS: (1) Insulin decreases neointimal growth after arterial injury
      independent of glucose-lowering or oral glucose administration and (2) oral
      sucrose per se affects neointimal growth.

PMID- 20145415
TI  - Enhanced matrix metalloproteinase activity in the spontaneously hypertensive rat:
      VEGFR-2 cleavage, endothelial apoptosis, and capillary rarefaction.
AB  - Besides an elevated blood pressure, the spontaneously hypertensive rat (SHR) has
      multiple microvascular complications including endothelial apoptosis with
      capillary rarefaction. The SHR also has elevated levels of proteolytic (e.g.
      matrix metalloproteinase, MMP) activity and apoptosis in microvascular cells
      compared to its normotensive control, but the specific enzymes involved and the
      molecular mechanism for apoptosis are unknown. We hypothesize that selected MMPs
      cleave the extracellular domain of vascular endothelial growth factor receptor-2
      (VEGFR-2), which in turn causes endothelial apoptosis and capillary rarefaction.
      Zymographic analysis shows that gelatinase (MMP-2 and MMP-9) and matrilysin (MMP
      7) activities are significantly enhanced in SHR plasma. The SHR has lower levels
      of the extracellular domains of VEGFR-2 in cardiac microvessels. Furthermore,
      application of plasma from the SHR, or purified MMP-9 and MMP-7 to naive cells
      causes cleavage of the extracellular domain of VEGFR-2. The receptor cleavage was
      blocked by broad-acting MMP inhibitors (GM6001 1 microM, EDTA 10 mM, or
      doxycycline 11.3 microM). Chronic MMP inhibition (doxycycline, 5.4 mg/kg/day, 24
      weeks) attenuated VEGFR-2 cleavage, endothelial apoptosis, and capillary
      rarefaction in the SHR. These results suggest elevated plasma MMP activities may
      cleave VEGFR-2, resulting in endothelial apoptosis and capillary rarefaction in
      the SHR.

PMID- 20145416
TI  - Mechanical stress modulates SOCS-1 expression in human vascular smooth muscle
      cells.
AB  - BACKGROUND: The growth-promoting effect of mechanical stress on vascular smooth
      muscle cells (VSMC) has been implicated in the progress of cardiovascular
      diseases related to elevated blood pressure. The underlying molecular mechanisms
      are, however, not completely defined. METHODS: We have studied primary human
      aortic VSMC using a model for multilateral stretch. Expression of the suppressor
      of cytokine signaling (SOCS) family member SOCS-1 and related molecular
      mechanisms were studied using TaqMan analysis, immunoblotting, protein silencing,
      specific cell treatment, immunoprecipitation and immunocytochemistry. RESULTS:
      Mechanical stretch inhibits SOCS-1 mRNA and protein expression. This effect was
      abolished by cell treatment with methyl-beta-cyclodextrin disrupting lipid rafts
      and with RGD peptide affecting integrins. Inhibition of integrin interaction with
      another cellular receptor, urokinase receptor (uPAR), as well as uPAR silencing
      also abolished stretch-induced SOCS-1 downregulation. Mechanical stretch resulted
      in uPAR redistribution to lipid rafts and in its colocalization with focal
      adhesion kinase (FAK). Stretch impairs polyubiquitination and proteosomal
      degradation of FAK leading to FAK upregulation in stretched VSMC. SOCS-1
      silencing and inhibition of proteosomal degradation simulate this effect.
      CONCLUSION: Our study identifies SOCS-1 as a novel participant involved in the
      propagation of mechanical stimuli in human VSMC, which might be relevant for the
      development of cardiovascular diseases.

PMID- 20145417
TI  - Prostaglandins and radical oxygen species are involved in microvascular effects
      of hyperoxia.
AB  - Hyperoxia causes vasoconstriction in most tissues, by mechanisms that are not
      fully understood. We investigated microvascular effects of breathing 100% oxygen
      in healthy volunteers, using iontophoresis to deliver acetylcholine (ACh) and
      sodium nitroprusside (SNP). Aspirin and vitamin C were used to test for
      involvement of prostaglandins and radical oxygen species. Forearm skin perfusion
      was measured using laser Doppler perfusion imaging. Results were analysed using
      dose-response modelling. The response to ACh was reduced by 30% during oxygen
      breathing compared to air breathing [0.98 (0.81-1.15) PU vs. 1.45 (1.30-1.60) PU,
      p < 0.001]. ED(50) values were unchanged [2.25 (1.84-2.75) vs. 2.21 (1.79-2.74),
      not significant]. Aspirin pre-treatment abolished the difference in response
      between oxygen breathing and air breathing [maximum: 1.03 (0.90-1.16) vs. 0.89
      (0.77-1.01), not significant; ED(50): 1.83 (1.46-2.30) vs. 1.95 (1.65-2.30), not
      significant]. ACh-mediated vasodilatation during 100% oxygen breathing was
      partially restored after pre-treatment with vitamin C. Breathing 100% oxygen did
      not change the microvascular response to SNP [1.45 (1.28-1.62) vs. 1.40 (1.26
      1.53), not significant]. These results favour the hypothesis that hyperoxic
      vasoconstriction is mediated by inhibition of prostaglandin synthesis. Radical
      oxygen species may be involved as vitamin C, independently of aspirin, partially
      restored ACh-mediated vasodilatation during hyperoxia.

PMID- 20145418
TI  - Neuroprotection in diabetic encephalopathy.
AB  - Increasing evidence has shown that diabetes may be associated with learning and
      memory deficits in humans. These cognitive disorders, called 'diabetic
      encephalopathy', can impair the daily performance of diabetic individuals. In
      recent years, some neuroprotective measures have been proposed to prevent
      diabetic neuropathology. This review attempts to show a summary of different
      experimental measures that have been described to improve the burden of diabetes
      in the central nervous system, particularly hippocampal formation.

PMID- 20145419
TI  - Traumatic brain injury may increase the risk for frontotemporal dementia through
      reduced progranulin.
AB  - Frontotemporal lobar degeneration with TAR-DNA-binding protein inclusions (FTLD
      TDP) is the most common pathological subtype of frontotemporal dementia (FTD).
      Mutations leading to a loss of function in the progranulin gene (PGRN) are the
      most common known cause of FTLD-TDP. In agreement with the proposed loss of
      function disease mechanism, several groups have reported decreased plasma levels
      of PGRN in patients carrying PGRN mutations compared to individuals without PGRN
      mutations. We propose that traumatic brain injury (TBI), an environmental factor,
      may also increase the risk of FTD by altering PGRN metabolism. TBI may lead to an
      increase in the central nervous system levels of microglial elastases, which
      proteolyze PGRN into proinflammatory products called granulins causing a
      reduction in PGRN levels. Hence, inhibiting microglial activation may have an
      important implication for the prevention of FTD in patients with TBI.

PMID- 20145421
TI  - Screening for diabetic retinopathy: a comparative trial of photography and
      scanning laser ophthalmoscopy.
AB  - AIMS: To evaluate the sensitivity and specificity of wide-field scanning laser
      ophthalmoscopy (WSLO) in the detection of referable diabetic eye disease, and to
      compare its performance with digital retinal photography. METHODS: Patients
      enrolled into the study underwent non-mydriatic WSLO imaging, then single- and
      dual-field mydriatic digital retinal photography, and examination with slit lamp
      biomicroscopy, the reference standard. Grading of retinopathy was performed in a
      masked fashion. RESULTS: A total of 380 patients (759 eyes) were recruited to the
      study. Technical failure rates for dilated single-field retinal photography, dual
      field retinal photography and undilated WSLO were 6.3, 5.8 and 10.8%,
      respectively (0.005 < p < 0.02 for photography vs. WSLO). The respective indices
      for screening sensitivity were 82.9, 82.9 and 83.6% (p > 0.2). Specificity was
      92.1, 91.1 and 89.5%, respectively (p > 0.2). CONCLUSIONS: Sensitivity and
      specificity for WSLO were similar to retinal photography. The technical failure
      rate was greater for the WSLO used in this study.

PMID- 20145420
TI  - RAGE does not affect amyloid pathology in transgenic ArcAbeta mice.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by brain accumulation of
      the amyloid-beta peptide (Abeta) that triggers a cascade of biochemical and
      cellular alterations resulting in the clinical phenotype of the disease. While
      numerous experiments addressed Abeta toxicity, the mechanisms are still not fully
      understood. The receptor for advanced glycation end products (RAGE) binds Abeta
      and was suggested to be involved in the pathological processes of AD. OBJECTIVE:
      Our purpose was to assess the effect of RAGE deletion on Abeta-related pathology.
      METHODS: We crossed RAGE knockout (RAGE(-/-)) mice with transgenic mice harboring
      both the Swedish and Arctic Abeta precursor protein mutations (arcAbeta mice). We
      assessed Abeta levels, Abeta brain deposition, Abeta-degrading enzyme activities,
      Abeta precursor protein expression and processing, number and morphology of
      microglia as well as cognitive performance of 6- and 12-month-old RAGE(-/
      )/arcAbeta, RAGE(-/-), arcAbeta and wild-type mice. RESULTS: RAGE(-/-)/arcAbeta
      mice had significantly lower levels of SDS- and formic-acid-extracted Abeta in
      the cortex and hippocampus, with concomitantly increased activity of insulin
      degrading enzyme at the age of 6 months. However, RAGE deletion could neither
      prevent the decline in cognitive performance nor the age-related cerebral
      accumulation of Abeta peptide. Furthermore, histological analysis revealed no
      difference in the microglia-occupied brain areas or microglial morphologies
      between RAGE(-/-)/arcAbeta and arcAbeta mice. CONCLUSIONS: Together, our results
      indicate that while the absence of RAGE was associated with increased insulin
      degrading enzyme activity in the brain, it was not sufficient to prevent or
      ameliorate cognitive deterioration, Abeta accumulation and microglial activation
      in the arcAbeta mouse model of AD.

PMID- 20145422
TI  - A promising therapeutic approach for treatment of posterior uveitis: recombinant
      T cell receptor ligand protects Lewis rats from acute and recurrent experimental
      autoimmune uveitis.
AB  - INTRODUCTION: Chronic autoimmune uveitis is a major cause of vision loss from
      intraocular inflammation in humans. In this study we report that a recombinant
      TCR ligand (RTL220) composed of the alpha1 and beta1 domains of MHC class II
      molecules linked to the uveitogenic interphotoreceptor retinoid-binding protein
      (IRBP) 1177-1191 peptide is effective in the suppression of acute and recurrent
      experimental autoimmune uveitis (EAU). MATERIAL AND METHODS: EAU was induced with
      IRBP1177-1191 peptide or by adoptive transfer of specific T cells in Lewis rats.
      The rats received 5 doses of RTL220 subcutaneously every other day starting at
      the onset of clinic signs of EAU. RESULTS: The administration of RTL220 resulted
      in a delayed onset and a significant amelioration of the disease severity at
      clinical levels and showed protection of the retina from inflammatory damage at
      histological levels. In treatment of recurrent EAU, RTL220 administrated at the
      first or second onset of clinical disease significantly inhibited EAU, modulated
      immune responses and provided protection from relapses of uveitis. The systemic
      and local proinflammatory cytokines were significantly reduced, including IL-17.
      There was local and systemic increase in IL-10 and reduction in the expression of
      the proinflammatory chemokines CCL2, CCL3 and CCL5. CONCLUSIONS: Our studies
      demonstrate a successful treatment of acute and recurrent EAU with RTL220, which
      effectively suppressed the recurrence of inflammation and reversed clinical and
      histological EAU by altering cytokine and chemokine expression. These findings
      strongly support a possible clinical application of this novel class of
      peptide/MHC class II drugs for patients with autoimmune uveitis.

PMID- 20145423
TI  - Aided air conduction threshold as a predictor of cochlear reserve in otosclerosis
      patients.
AB  - Otosclerosis classically presents with conductive deafness. However, mainly in
      older patients or those with a progressive (active) form of this disease, it
      presents with elevated bone conduction (BC) thresholds. In many cases, an
      elevation in the BC threshold during otosclerosis is not a true indicator of
      'cochlear reserve' and this apparent loss can be corrected by surgery. It is
      generally accepted that in those patients, elevated BC thresholds are not due to
      pure sensorineural hearing loss but to the Carhart effect. Speech discrimination
      tests are routinely done, and the results of these tests determine if a patient
      is a good candidate for surgery. In most institutions, those with poor speech
      discrimination scores are considered to be poor candidates due to inadequate
      cochlear reserve. Using hearing-aid-assisted pure-tone audiometry, we developed
      an accurate method to identify suitable candidates for surgery among the patients
      with elevated BC thresholds. This method is meant to complement speech
      discrimination tests in predicting the success of surgery in those patients.
      Different variables render speech discrimination tests unreliable in many
      patients. The rationale behind the current study was the lack of an easy and
      accurate clinical method to determine if a patient has a good cochlear reserve,
      and to predict the postoperative hearing threshold outcome.

PMID- 20145424
TI  - Preprandial single oral dose of sitagliptin does not affect circulating ghrelin
      and gastrin levels in normal subjects.
AB  - AIMS: To determine the effect of an oral dose of sitagliptin on the secretion of
      ghrelin and gastrin hormones. METHODS: Ten healthy volunteers were recruited in
      this study. A baseline blood sample was drawn before oral dosing with a 100-mg
      tablet of sitagliptin. Two blood samples were obtained 0.5 and 1 h after dosing.
      Three additional postprandial blood samples were drawn at 0.5, 1, and 2 h.
      Radioimmunoassay was used for determining hormonal levels. A Student's t test,
      Pearson correlation analysis, and multivariate approach to repeated-measures
      analysis of variance were used for statistics. RESULTS: After sitagliptin dosing,
      but before the meal, there was no significant change in circulating ghrelin,
      gastrin, insulin, and glucose levels. Only after meal loading was there a
      progressive and persistent decline in ghrelin levels until the end of the study,
      while a rapid and temporary rise in gastrin, insulin, and glucose levels at 0.5 h
      was observed. The levels of gastrin, insulin, and glucose then declined
      progressively. CONCLUSIONS: Preprandial oral dose of sitagliptin does not affect
      circulating ghrelin, gastrin, insulin, and glucose concentrations in normal
      subjects. Decreased ghrelin and increased gastrin and insulin levels occurred
      only after meal loading. These results support the theory that sitagliptin might
      not cause appetite-enhanced body weight gain and insulin-induced hypoglycemia.

PMID- 20145425
TI  - Inhibitory effect of paclitaxel on endothelial cell adhesion and migration.
AB  - The long-term success of percutaneous coronary interventions has been limited by
      restenosis. Therefore, local delivery of paclitaxel, an antiproliferative agent,
      using drug-eluting stents has been applied to prevent in-stent restenosis.
      However, paclitaxel not only inhibits smooth muscle cell proliferation, but also
      delays re-endothelialization of the damaged site, which may cause potentially
      life-threatening cardiovascular adverse events, especially late and very late
      stent thrombosis. We investigated the role of paclitaxel in endothelial cell line
      ECV304 adhesion and migration. Accordingly, changes in vasodilator-stimulated
      phosphoprotein protein (VASP) phosphorylation and cAMP-dependent protein kinase
      activity during ECV304 cell detachment and reattachment were investigated as
      well. The results showed that the decrease in VASP phosphorylation paralleled the
      inhibition of cAMP-dependent protein kinase (PKA) activity in the presence of
      paclitaxel (10 microg/l). Cell adhesion assay and two- and three-dimensional cell
      migration assays were performed to determine the effect of paclitaxel on the
      adhesion and migration of ECV304 cells. Paclitaxel significantly suppresses the
      adhesion (p < 0.05) and migration of ECV304 cells (p < 0.05). These data suggest
      that the inhibitory effect of paclitaxel may be produced by decreasing the
      phosphorylation of VASP via inhibition of PKA activity during ECV304 cell
      adhesion and migration.

PMID- 20145426
TI  - Functional and histologic assessment of rat gastric mucosa after chronic
      treatment with sulphurous thermal water.
AB  - The effect of a chronic (4 weeks) administration of sulphurous thermal water on
      gastric acid secretion and mucosal defense was investigated in rats. Animals were
      randomized to receive daily intake of tap water or of thermal water obtained from
      a local spa center (Tabiano, Parma, Italy). Rats were followed for one month as
      for water and food consumption, body weight and general conditions. At the end of
      the watering period, the following study protocols were carried out: (a) study of
      basal and stimulated gastric acid secretion under general anesthesia, and (b)
      study of the gastric mucosal resistance against the damage induced by ethanol and
      indomethacin in conscious rats. Basal acid secretion and the acid response to
      pentagastrin or to histamine were similar in rats assuming ordinary drinking
      water or thermal water. As for resistance to gastric damage, histological, but
      not macroscopic, evaluation revealed that rats which assumed thermal water were
      slightly more resistant to the gastrolesive effect of ethanol (either absolute or
      diluted). Again, when indomethacin was used as a noxious stimulus, no difference
      was noted between the two groups as for macroscopic damage; only a nonsignificant
      reduction of damage was observed histologically in stomachs of rats assuming
      thermal water. In conclusion, these results indicate that chronic treatment of
      rats with thermal water, rich in sulphur compounds, may have only minimal effects
      on the rat gastric mucosa and did not significantly affect mucosal defense
      mechanisms. The observed tendency to gastroprotection would possibly need further
      investigation with longer periods of administration.

PMID- 20145427
TI  - Risedronate versus alendronate in older patients with osteoporosis at high risk
      of fracture: an Italian cost-effectiveness analysis.
AB  - BACKGROUND AND AIMS: This evaluation of the cost-effectiveness of risedronate vs
      generic alendronate is based on effectiveness data from a large real practice
      study. Applying a published cost-effectiveness model, we found that risedronate
      is cost-effective vs generic alendronate in an Italian population aged > or =65
      years, and becomes dominant, saving costs and avoiding fractures, in patients
      aged > or =75 years. The aim of this work was to assess the cost-effectiveness
      and health utility of risedronate vs generic alendronate in clinical practice in
      Italy, using effectiveness data from the REAL study. METHODS: A pre-existing
      model of osteoporosis was used to predict numbers of fractures, quality-adjusted
      life-years (QALYs), and costs associated with risedronate or alendronate
      treatment in post-menopausal (PMO) women aged > or =65 years with a previous
      vertebral fracture, within the Italian National Health System (NHS). Duration of
      treatment with risedronate or alendronate was assumed to occur for one year and
      patients were followed for an additional five years to capture longterm costs and
      outcomes, with a discount rate of 3% for costs and outcomes. Comprehensive
      sensitivity analyses were run. RESULTS: The lower fracture rate among risedronate
      patients with respect to alendronate patients resulted in savings of euro 19,083,
      a reduction of 8.91 hip fractures and an associated benefit of 7.46 QALYs, in an
      Italian cohort of 1,000 patients. Sensitivity analyses confirmed the robustness
      of these results. CONCLUSIONS: This economic analysis showed that risedronate is
      a cost-effective treatment in a population of Italian women aged 65 years and
      older at high risk of PMO-related fractures. Risedronate becomes dominant over
      generic alendronate in patients of 75 years or older and its cost-effectiveness
      even appears improved in patients with BMD score < or = -3 or < or = -3.5,
      with/without maternal history of fractures. Risedronate should be considered as a
      cost-effective option vs generic alendronate, in the Italian NHS' perspective.

PMID- 20145430
TI  - Circulating endothelial progenitor cells, Th1/Th2/Th17-related cytokines, and
      endothelial dysfunction in resistant hypertension.
AB  - INTRODUCTION: A possible link between chronic vascular inflammation and arterial
      hypertension is now an object of intensive studies. OBJECTIVE: To compare
      Th1/Th2/Th17 cells-related cytokines, circulating endothelial progenitor cells
      (EPC), and endothelial function in subjects with resistant arterial hypertension
      (RAH) and controlled arterial hypertension (CAH). METHODS: Blood pressure was
      measured by electronic sphygmomanometer. EPC were identified as
      CD34+/CD133+/kinase insert domain receptor (KDR)+ cells by flow cytometry.
      Th1/Th2/Th17 cells-related cytokines were identified using the Human Th1/Th2/Th17
      Cytokines MultiAnalyte ELISArray Kit. Endothelium-dependent (FMD) vasodilatation
      of brachial artery was measured by Doppler ultrasound scanning. RESULTS: RAH
      group (n = 20) and CAH group (n = 20) and 17 healthy individuals (control group)
      were recruited. In the RAH group, lower blood levels of EPC number (42.4 +/- 16.7
      cells/mL) and EPC% (0.19 +/- 0.08%) were observed than in the CAH group (93.1 +/-
      88.7 cells/mL; P = 0.017; 0.27 +/- 0.17; P = 0.036) and control group (68.5 +/-
      63.6 cells/mL; P < 0.001; 0.28 +/- 0.17%; P = 0.003), respectively. Plasma
      transforming growth factor-beta1 levels were significantly higher in the RAH
      group (1767 +/- 364 pg/mL) than in the CAH group (1292 +/- 349; P < 0.001) and in
      control group (1203 +/- 419 pg/mL; P < 0.001). In the RAH group, statistically
      significant negative correlation was observed between systolic blood pressure and
      EPC% (r = -0.72, P < 0.01). FMD in the RAH group was significantly lower (5.5 +/-
      0.8%) than in the CAH group (9.2 +/- 1.4; P < 0.001) and in healthy controls
      (10.1 +/- 1.1%; P < 0.001). CONCLUSION: RAH is characterized by reduced
      circulating EPC, substantial endothelial dysfunction, and increased plasma
      transforming growth factor-beta1 levels.

PMID- 20145431
TI  - Early nephrology referral is associated with prolonged survival in hemodialysis
      patients even after exclusion of lead-time bias.
AB  - BACKGROUND: Early nephrology referral (ER) has been suggested to lower morbidity
      and mortality in dialysis patients, but the nature of the association has been
      criticized as possibly because of lead-time bias. This study aims to evaluate if
      ER is associated with improved survival of hemodialysis patients when the lead
      time bias is excluded. METHODS: A total of 192 hemodialysis patients from a
      medical center and a regional hospital were enrolled in the period from January
      1997 to December 2006. ER and late referral (LR) were defined as referral to
      nephrologists greater or less than 6 months, respectively, before the initiation
      of hemodialysis. Follow-up of clinical course in all patients was timed from the
      date at which estimate glomerular filtration rate was estimated to be 15
      mL/min/1.73m. The relative overall survival was analyzed by Cox-regression
      adjusted for their demographic and comorbid conditions RESULTS: Compared with LR
      patients, ER patients were less likely to have hypoalbuminemia in the beginning
      of hemodialysis, more likely to have received erythropoietin or phosphate binder
      therapy, more likely to have a vascular access created before the first
      hemodialysis, and had a slower rate of renal function decline before
      hemodialysis. In multivariate analysis, LR (hazard ratio: 2.827; P = 0.049) and
      diabetes mellitus were both independently associated with increased mortality
      risk. The survival benefits of ER seem to be originated from the period before
      initiation of renal replacement therapy. CONCLUSIONS: Our findings show that ER
      is significantly associated with prolonged survival after exclusion of lead-time
      bias, which is consistent with ER being associated with better clinical outcomes
      in hemodialysis patients.

PMID- 20145432
TI  - Effect of exercise therapy on monocyte and neutrophil counts in overweight women.
AB  - INTRODUCTION: It has been well known that physical inactivity is associated with
      a significantly higher incidence of coronary artery disease. This study aimed to
      test our hypothesis that endurance aerobic exercise training has cardiovascular
      protective effects as a result of inhibiting inflammatory processes. METHODS:
      Forty-two overweight women [age, 53.4 +/- 9.8 years; body mass index (BMI), 28.0
      +/- 2.8] received electric bicycle ergometer exercise therapy at the lactate
      threshold intensity for 30 to 60 minutes per day, 1 to 6 times per week for 6
      weeks. The exercise training was performed within the possible load (exercise
      duration and frequency) for each subject. RESULTS: Leukocyte, monocyte, and
      neutrophil counts significantly decreased after the exercise therapy (P < 0.05).
      In simple regression analysis, percent changes in monocyte and neutrophil counts
      were correlated with percent changes in fasting triglyceride levels, insulin
      sensitivity index, BMI, and maximal oxygen uptake (VO2max). In stepwise multiple
      regression analysis, the percent change in monocyte counts was associated with
      percent changes in fasting triglyceride and VO2max (r = 0.368, P < 0.001), and
      the percent change in neutrophil counts was associated with percent changes in
      insulin sensitivity index and BMI (r = 0.292, P < 0.001). CONCLUSIONS: Endurance
      aerobic exercise training can influence some inflammatory processes. Furthermore,
      increased aerobic capacity may be antiinflammatory and have cardiovascular
      protective effects in overweight women.

PMID- 20145434
TI  - Landmark publication from The American Journal of the Medical Sciences:
      Hereditary angio-neurotic oedema. 1888.

PMID- 20145433
TI  - Comparative effects of benidipine and amlodipine on proteinuria, urinary 8-OHdG,
      urinary L-FABP, and inflammatory and atherosclerosis markers in early-stage
      chronic kidney disease.
AB  - INTRODUCTION: We examined the effects of 2 calcium channel blockers, benidipine
      (T-, L-, and N-type) and amlodipine (L- and N-type), on renal, inflammatory,
      oxidative, and atherosclerosis markers in hypertensive patients with mild chronic
      kidney disease (CKD). METHODS: Forty hypertensive patients with CKD were assigned
      randomly to either of the 2 treatments: 8 mg benidipine once daily (n = 20, group
      A) or 5 mg amlodipine once daily (n = 20, group B). Treatment was continued for
      12 months. Blood pressure, serum creatinine, estimated glomerular filtration
      rate, urinary protein excretion, urinary liver-type fatty acid-binding protein,
      interleukin-6, high mobility group box-1 protein, urinary 8-hydroxy-2'
      deoxyguanosine, pulse wave velocity, intima-media thickness, and blood asymmetric
      dimethylarginine were monitored. RESULTS: Blood pressure decreased equally in
      both groups (P < 0.001, at 6 and 12 months versus before treatment). Serum
      creatinine and estimated glomerular filtration rate changed little during the
      experimental period in each group. However, urinary protein excretion (P <
      0.001), urinary liver-type fatty acid-binding protein (P < 0.001), urinary 8
      hydroxy-2'-deoxyguanosine (P < 0.001), blood interleukin-6 (P < 0.001), blood
      high mobility group box-1 (P < 0.05), and pulse wave velocity (P < 0.01)
      decreased more in group A than in group B with 12 months of treatment. The
      percent reductions in intima-media thickness and blood asymmetric
      dimethylarginine were significantly greater in group A than in group B (P <
      0.001). CONCLUSIONS: Benidipine is more effective than amlodipine for protecting
      renal function and potentially for ameliorating atherosclerosis in hypertensive
      patients with mild CKD. T-type calcium channel blockers may be effective in
      patients with CKD.

PMID- 20145435
TI  - Genius at work: Osler's 1888 article on hereditary angioedema.

PMID- 20145436
TI  - Positive pregnancy tests in a postmenopausal woman due to beta-human chorionic
      gonadotropin production by multiple myeloma.
AB  - Extensive immunochemical characterization has shown that the free beta subunit of
      hCG (betahCG) can be produced by common epithelial tumors, including lung, colon,
      and bladder. However, the expression of beta-human chorionic gonadotropin (hCG)
      in hematologic malignancies and its significance is largely unknown. We present
      an extremely rare case of positive serum betahCG in a postmenopausal woman with
      relapsed, refractory multiple myeloma with myeloma cells expressing betahCG on
      immunohistochemical stain.

PMID- 20145438
TI  - Omega-6 and omega-3 fatty acids: partners in prevention.
AB  - PURPOSE OF REVIEW: This review addresses the cardiovascular benefits of the two
      families of essential polyunsaturated fatty acids (FAs): omega-6 and omega-3. The
      former (and the shorter chain species of the latter) are found in vegetable oils
      and nuts, whereas the longer chain omega-3 FAs are found in fish oils. Although
      most clinicians understand that the omega-3 FAs are beneficial, there have been
      calls in the popular press to reduce the intake of the omega-6 FAs because of
      presumed proinflammatory and prothrombotic effects. RECENT FINDINGS: The American
      Heart Association's Nutrition Committee has published two 'Science Advisories',
      one in 2002 on omega-3 FAs and a new one on omega-6 FAs. Both considered a wide
      variety of data regarding their effects on cardiac risk. SUMMARY: The AHA
      concludes that Americans need to increase their intake of long-chain omega-3 FAs
      and that they should maintain (and possibly even increase) their intakes of omega
      6 FAs. For the omega-3 FAs, a healthy target intake is about 500 mg per day
      (whether from oily fish or fish oil capsules) and for linoleic acid,
      approximately 15 g per day (12 g for women and 17 g for men). Achieving healthy
      intakes of both omega-6 and omega-3 FAs is an important component of the
      nutritional prevention and treatment of coronary heart disease.

PMID- 20145439
TI  - Brain arachidonic acid uptake and turnover: implications for signaling and
      bipolar disorder.
AB  - PURPOSE OF REVIEW: Arachidonic acid was first detected in the brain in 1922.
      Although earlier work examined the role of arachidonic acid in growth and
      development, more recent advancements have elucidated roles for arachidonic acid
      in brain health and disease. RECENT FINDINGS: In this review, we summarize
      evidence demonstrating that unesterified arachidonic acid in the plasma pool,
      which is supplied in part from adipose, is readily taken up and incorporated into
      brain phospholipids. By labeling plasma unesterified arachidonic acid, it is
      possible to trace the subsequent release of arachidonic acid from brain
      phospholipids upon neuroreceptor-mediated release by phospholipase A2 in response
      to drugs and neuroinflammation in rodents. With the synthesis of 11C labeled
      fatty acids, brain arachidonic acid signaling can now be measured in humans with
      position emission tomography. Arachidonic acid signals are known to regulate
      important biological functions, including neuroinflammation and excitotoxicity,
      and we focus on how the brain arachidonic acid cascade is a common target of
      drugs used to treat bipolar disorder (e.g. lithium, carbamazepine and valproate).
      SUMMARY: A better understanding of the regulation of arachidonic acid uptake into
      the brain and the brain arachidonic acid cascade could lead to new imaging
      techniques and the identification of novel therapeutic targets in excitotoxicity,
      neuroinflammation and bipolar disorder.

PMID- 20145440
TI  - Current Opinion in Clinical Nutrition and Metabolic Care. Current world
      literature.

PMID- 20145442
TI  - Current world literature.

PMID- 20145444
TI  - Current Opinion in Nephrology and Hypertension. Current world literature.

PMID- 20145445
TI  - Colorectal cancer: the tide is finally turning.

PMID- 20145446
TI  - A critical review of self-management and educational interventions in
      inflammatory bowel disease.
AB  - The purpose of this study was to examine self-management and educational
      interventions developed to support people with inflammatory bowel disease (IBD)
      and to identify which type of intervention seems to be most effective. The search
      was deliberately overinclusive to capture studies that evaluated educational and
      self-management interventions. The following databases were searched: MEDLINE,
      Embase, CINAHL, PsycINFO, the National Research Register, and Cochrane. Twenty
      three studies were included. Thirteen of these were randomized controlled trials.
      The content of the interventions reviewed varied widely. As expected, it is the
      three studies that have explicitly labeled themselves as self-management
      interventions that have incorporated the greatest number of self-management
      techniques. Two of these studies reported the greatest number of improved
      outcomes in relation to symptom reporting, psychological well-being, and
      healthcare resource use. There is clearly a role for information in IBD, but this
      review supports research in other conditions that shows that education cannot be
      assumed to lead to improvements in health and well-being. Much of the research in
      this area focuses on education rather than self-management. Where self-management
      techniques have been applied, the findings tend to be more promising.
      Gastroenterology nurses (or in the United Kingdom, IBD specialist nurses) may be
      best placed to facilitate self-management in this group.

PMID- 20145447
TI  - Endoscopic procedure with a modified Reiki intervention: a pilot study.
AB  - This pilot study examined the use of Reiki prior to colonoscopy to reduce anxiety
      and minimize intraprocedure medications compared with usual care. A prospective,
      nonblinded, partially randomized patient preference design was employed using 21
      subjects undergoing colonoscopy for the first time. Symptoms of anxiety and pain
      were assessed using a Likert-type scale. Between-group differences were assessed
      using chi-square analyses and analysis of variance. There were no differences
      between the control (n = 10) and experimental (n = 11) groups on age (mean = 58
      years, SD = 8.5) and gender (53% women). The experimental group had higher
      anxiety (4.5 vs. 2.6, p = .03) and pain (0.8 vs. 0.2, p = .42) scores prior to
      colonoscopy. The Reiki intervention reduced mean heart rate (-9 beats/minute),
      systolic blood pressure (-10 mmHg), diastolic blood pressure (-4 mmHg), and
      respirations (-3 breaths/minute). There were no between-group differences on
      intraprocedure medication use or postprocedure physiologic measures. Although the
      experimental group patients had more symptoms, they did not require additional
      pain medication during the procedure, suggesting that (1) anxious people may
      benefit from an adjunctive therapy; (2) anxiety and pain are decreased by Reiki
      therapy for patients undergoing colonoscopy, and (3) additional intraprocedure
      pain medication may not be needed for colonoscopy patients receiving Reiki
      therapy. This pilot study provided important insights in preparation for a
      rigorous, randomized, controlled clinical trial.

PMID- 20145448
TI  - Evaluation of the risk of transmission of bacterial biofilms and Clostridium
      difficile during gastrointestinal endoscopy.
AB  - Recent attention has focused on the potential for the transmission of bacterial
      biofilms, Clostridium difficile, and other types of pathogenic spore-forming
      bacteria during gastrointestinal (GI) endoscopy. This study investigates whether
      GI endoscopy is a risk factor for the transmission of bacterial biofilms and the
      endospores or vegetative cells of pathogenic spore-forming bacteria including C.
      difficile. The medical literature was reviewed to evaluate the risk of the
      transmission of these infectious agents during GI endoscopy. No cases of a GI
      endoscope transmitting the endospores or vegetative cells of C. difficile or
      another type of pathogenic spore-forming bacterium were identified during this
      review. Also, no studies were identified during this review that document a case
      of infection causally linked to a bacterial biofilm that formed on the internal
      surfaces of and was transmitted by a GI endoscope that was reprocessed in
      accordance with currently accepted and well-established reprocessing standards.
      Gastrointestinal endoscopy is not reported to be a risk factor for the
      transmission of bacterial biofilms, C. difficile, or the endospores (and
      vegetative cells) of any other type of pathogenic spore-forming bacterium (or any
      type of infectious agent). Strict adherence to currently accepted and well
      established reprocessing standards is necessary to prevent transmission of
      biofilms, C. difficile, and other infectious agents during GI endoscopy.

PMID- 20145449
TI  - Patients' perspective of factors influencing quality of life while living with
      Crohn disease.
AB  - Crohn disease is a chronic inflammatory bowel disease of unknown etiology. The
      chronic, relapsing nature of Crohn disease produces physical, psychological, and
      social stress. The disease occurs early in life, and the effects of Crohn disease
      on daily life are associated with symptom burden; thus, managing their disease
      and coping with its impact is a lifelong process for sufferers. This study was
      undertaken to identify and describe the meaning of quality of life in patients
      with Crohn disease. Using a grounded theory methodology, 11 interviews were
      performed with 6 men and 5 women, 29-83 years of age, all suffering from Crohn
      disease. The experience of quality of life was associated with limitations in
      daily activity, the major theme that emerged from the analysis. Quality of life
      varied depending on how the patient managed limitations related to the symptoms
      of the disease. The categories of self-image, confirmatory relations,
      powerlessness, attitude toward life, and sense of well-being were conceptualized
      as the dominant themes derived from the data. When caring for these patients, it
      is important to identify limitations and provide support so that patients are
      able to maintain a daily life that can be perceived as normal and routine.

PMID- 20145451
TI  - A pilot study to test the practicality and efficiency of methods used to evaluate
      colon cleansing in an inpatient setting.
AB  - The purpose of the study was to test measurement methods in an inpatient setting
      for future use in a multisite study about bowel cleansing before colonoscopy.
      Because the multisite study used data collectors at distant geographic points who
      might have limited time to devote to data collection, the forms needed to be
      tested for practicality and efficiency. The data collection procedures worked
      well, but we experienced unexpected difficulties recruiting inpatients. We also
      found that we need to direct more efforts toward building the staff nurses'
      enthusiasm for the study because they help with data collection.

PMID- 20145452
TI  - Absorbing what is said.

PMID- 20145453
TI  - Bullous lesions in a woman suffering from ulcerative colitis.

PMID- 20145454
TI  - An ethical dilemma: decision making about liver transplantation in a patient with
      schizophrenia.

PMID- 20145455
TI  - When your best is not good enough.

PMID- 20145456
TI  - Developing a journal club that impacts practice.

PMID- 20145457
TI  - SGNA Standards: standards of infection control in reprocessing of flexible
      gastrointestinal endoscopes.

PMID- 20145458
TI  - SGNA position statement: reprocessing of water bottles used during endoscopy.

PMID- 20145460
TI  - Management recruiting: inside versus outside.

PMID- 20145461
TI  - Hospital in-house laboratories: examining the external environment.
AB  - As hospitals fight for their portion of reimbursed health care expenditures, it
      will become increasingly necessary to investigate alternative funding mechanisms.
      In-house laboratories, which have likely been seen in the past as pure cost
      centers, can be repositioned to provide additional revenue to hospitals. This
      opportunity for in-house laboratories to be remade into profit centers is
      predicated upon a thorough understanding of the environmental factors affecting
      hospital laboratories. This article examines 4 distinct environmental factors:
      demographic and socioeconomic trends, reimbursement and financing, government
      policy, and clinical events. Each of these external environmental factors
      provides 2 broad sources of interest to hospitals and their in-house laboratory
      components: opportunities on which to capitalize and hazards against which to
      defend.

PMID- 20145462
TI  - Medical response planning for pandemic flu.
AB  - This quantitative research study evaluates the health care infrastructure
      necessary to provide medical care in US hospitals during a flu pandemic. These
      hospitals are identified within the US health care system because they operate
      airborne infectious isolation rooms. Data were obtained from the 2006 American
      Hospital Association annual survey. This data file provides essential information
      on individual US hospitals and identifies the health care capabilities in US
      communities. Descriptive statistics were evaluated to examine hospitals with the
      appropriate infrastructure to treat a flu pandemic. In addition, geographic
      information system software was used to identify geographic areas where essential
      infrastructure is lacking. The study found 3,341 US hospitals operate airborne
      infectious isolation rooms, representing 69% of reporting hospitals. The results
      also indicate that those hospitals with airborne infectious isolation rooms are
      larger and are located in metropolitan areas. The study has managerial
      implications associated with local medical disaster response and policy
      implications on the allocation of disaster resources.

PMID- 20145463
TI  - Critical access hospital chief executive officer turnover: implications and
      challenges for governing boards.
AB  - Small rural hospitals, categorized as critical access hospitals (CAHs), are
      essential to the provision of health care in rural areas of the United States.
      Critical access hospitals, however, are faced with numerous challenges to their
      survival that are unique to their role as a rural health care provider. One of
      the most significant of these challenges involves the retention of well-qualified
      chief executive officers (CEOs). Following an assessment of the negative
      implications associated with CEO turnover, the study utilizes survey data
      obtained from CAHs experiencing CEO turnover to suggest strategies that can be
      implement by CAH governing board to retain CEO leadership and mitigate the
      negative impact of CEO turnover. A key issue identified by the authors involves
      the critical role played by CEO-board relationships and the need for board
      leadership to create a culture and environment that promotes a strong working
      relationship and clear expectations between the CAH board and CEO.

PMID- 20145464
TI  - Consumer-directed health care: understanding its value in health care reform.
AB  - The purpose of this article is to describe the importance of consumer-directed
      health care as the essential strategy needed to lower health care costs and
      support its widespread adoption for making significant strides in health care
      reform. The pros and cons of health care consumerism are discussed. The intent is
      to show that the viability of the US health care system depends on the
      application of appropriate consumer-directed health care strategies.

PMID- 20145465
TI  - Trust: the sublime duty in health care leadership.
AB  - Trust is the essence of human social existence. From the moment of birth, trust
      is the basic component in any human relationship and interaction. Trust is the
      Holy Grail for human confidence in others. From human survival to organizational
      survival, trust is the primordial bond. No organization is more dependent on
      trust than health care. This article views trust as the most basic fundamental
      quality for leadership. Trust is a sublime duty of a leader and the leadership of
      an organization. Leadership sets the culture of trust. Trust is the one quality
      that is essential for guiding an organization toward serving others. This article
      addresses trust from many perspectives. Trust is viewed from our subordinates,
      our peers, our superiors, and the public we serve. This article postulates how
      trust in an organization is the sublime duty of leadership that unites all human
      understanding and without it destroys all human relationships.

PMID- 20145467
TI  - Your workers may be contingent, but your liability for them is certain: part I:
      employment status and fair labor standards act issues.
AB  - Hiring contingent workers can significantly help health care employers reduce
      labor costs while maintaining the staff required for quality patient care.
      However, a number of federal laws create legal landmines that await the
      unsuspecting employer. The purpose of this article was to familiarize health care
      employers with some of the rapidly evolving legal issues that surround the use of
      contingent workers.

PMID- 20145468
TI  - Factors associated with financial distress of nonprofit hospitals.
AB  - Financial distress can have a detrimental influence on the performance of
      hospitals. Hospital management needs to monitor potential financial distress
      effectively and know how it will respond depending on the severity of the
      circumstances. This study examined the multiple factors that may explain the
      financial distress of nonprofit hospitals during 1998 to 2001 and discussed their
      importance. To obtain more robust results, financial distress was assessed in 2
      ways: first, financial strength index was used to incorporate 4 financial
      dimensions including profitability, liquidity, leverage, and physical facilities;
      second, cash flow (CF) was used to address the issues of accrual-based accounting
      in hospitals. This study finds that decrease in occupancy rate and increase in
      Medicaid payer mix, health maintenance organization penetration, market
      competition, physician supply, and percentage of the elderly are associated with
      increased likelihood of financial distress of urban hospitals. Increases in both
      Medicare and Medicaid payer mix, however, are related to higher likelihood of
      financial distress of rural hospitals.

PMID- 20145469
TI  - Allied health students' perceptions of effective clinical instruction.
AB  - Students of allied health who have positive clinical education experiences often
      accept employment offered by their clinical sites. Most allied health
      professionals are not trained to be educators; to improve student clinical
      experiences, students were surveyed regarding their learning experiences during
      clinical internships. This study examined the teaching abilities and professional
      development training needs of clinical supervisors as identified by student
      perceptions. Results were compared with the results of the clinical supervisors'
      perceptions of themselves. A survey addressed the students' perceptions of the
      clinical supervisors' teaching skills. Results revealed that both students and
      clinical supervisors identified similar professional development training needs
      as they related to the improvement of teaching skills. The identified needs were
      understanding different learning styles, planning learning experiences prior to
      students' arrival, giving feedback, and assessing student skills based on
      learning goals. Students and clinical supervisors agreed on the areas that need
      to be addressed to improve the learning experiences in clinical education.
      Continuing education courses should focus on clinical supervisors' teaching
      skills, especially teaching methodology that focuses on students' different
      learning styles, how to plan learning experiences, and how to assess students'
      skills based on set learning goals.

PMID- 20145470
TI  - Cardiovascular supply cost negotiations: partnering for the future.
AB  - As a major expense driver to cardiovascular programs, supply costs related to
      electrophysiology and cardiac catheterization procedures directly link to the
      overall financial health of organizations associated with those programs. Because
      of this, it is important that institutions establish a logical and resolute
      approach to obtaining supply pricing that maximizes cost-saving opportunities,
      buffers their organizations from escalating costs related to the advances in
      available technologies, defines supply chain expectations while preserving
      clinicians' access to high-quality cardiovascular supplies, and maintains the
      availability of the full spectrum of products to our physicians, referring
      physicians, and patients. In a joint effort with physicians, administration, and
      suppliers, and in the spirit of partnership, the University of Michigan Health
      System has developed and implemented such a model that illustrates the
      opportunities to be gained.

PMID- 20145471
TI  - The impact of education regarding the needs of pediatric leukemia patients'
      siblings on the parents' knowledge and practice.
AB  - A study was undertaken to determine the effect of educational intervention on
      parents' knowledge and performance of the social needs of the healthy siblings of
      the pediatric leukemia patients. Inadequate care and attention to siblings of
      pediatric leukemia patients might result in psychosomatic disorders. Parents'
      knowledge on prevention of such disorders is of great importance. The study
      proposed to determine the effects of educational intervention concerning parents.
      Sixty parents of pediatric leukemia patients entered this study. The subjects
      were selected using convenient sampling method and were randomly categorized into
      2 groups: experimental and control. Data were collected before, 1 hour after, and
      2 months after the intervention, using a questionnaire. The educational program
      was arranged in 3 sessions, each lasting 45 to 60 minutes using group discussion
      and lectures for the parents of the experimental group. Then, the parents were
      instructed individually, if necessary. The mean scores of the parents' knowledge
      in the experimental and control groups before the intervention were 5.8 and 6.2,
      respectively. One hour after instruction, the mean rose to 12.8 and 6.4, and 2
      months later to 13.3 and 6.5 (p < .00l). The family performance of 87.2% of the
      parents in the experimental group and 36.4% of the control group toward the
      siblings of the sick child was appropriate 2 months after the intervention.
      Therefore, educational intervention increased the knowledge of the parents of
      pediatric leukemia patients about the needs of the healthy siblings and how to
      meet them. It is recommended that educational programs be arranged for parents so
      that the quality of life in the healthy children can be improved.

PMID- 20145472
TI  - HIPAA: SOP: HIPAA as standard operating procedures.
AB  - Upon the debut of the Health Insurance Portability and Accountability Act
      (HIPAA), many health care managers felt that the implementation process would be
      too expensive, arduous, and time-consuming. Now, several years later, it is clear
      that the way to manage HIPAA is to make it a part of one's standard operating
      procedures. Using this approach, HIPAA is cost-effective, manageable, and
      efficient. Health care managers can utilize the step-by-step procedures presented
      here to efficaciously implement and manage HIPAA.

PMID- 20145473
TI  - Self-management: key to success as a manager.
AB  - Self-management for the working manager must begin with a brutally honest self
      evaluation followed by a stubbornly determined effort to change. In the process,
      it is necessary to put oneself in perspective relative to the management role and
      put management itself into perspective for what it really is and what its
      requirements demand of the individual manager. It is necessary to examine one's
      capabilities and one's likes and dislikes as they relate to the management role
      and do something about these as circumstances demand. Self-management also
      requires recognizing the essential balance between the individual as a manager
      and as a knowledgeable specialist in some occupation or profession. Improvement
      in self-management requires dramatic change in some habits and involves self
      assessment of one's initiative, personal organization, and management of time.
      Lasting improvement in self-management is never absolutely complete; it will be a
      continuing part of day-to-day existence for as long as the individual remains a
      manager.

PMID- 20145474
TI  - Terror in a child's eyes.

PMID- 20145475
TI  - Of pathways and pipelines: the moral imperative of "poverty grown up".

PMID- 20145476
TI  - Poverty grown up: how childhood socioeconomic status impacts adult health.
AB  - Socioeconomic status and health status are directly related across the world.
      Children with low-socioeconomic status not only experience greater health
      problems in childhood but also aspects of their socioeconomic status become
      biologically incorporated through both critical periods of development and
      cumulative effects, leading to poor health outcomes as adults. We explore 3 main
      influences related to child's socioeconomic status that impact long-term health:
      the material environment, the social environment, and the structural or community
      environment. These influences illustrate the importance of clinical innovations,
      health services research, and public policies that address the socioeconomic
      determinants of these distal health outcomes.

PMID- 20145479
TI  - Empowering girls in Sierra Leone: initiation into the Bondo society.

PMID- 20145477
TI  - Gender variant and gender dysphoria in two young children.

PMID- 20145480
TI  - Tourette syndrome in Indian Ayurvedic medical practice.

PMID- 20145481
TI  - Predicting mental health and well-being in adulthood.
AB  - Although previous research focused on identifying risk factors for mental
      disorders (or ill-being), recent research has demonstrated a shift towards
      factors predicting mental well-being. A series of variables from a longitudinal
      study was used to compare 2 interpretations of mental well-being, namely mental
      health, defined as lack of DSM caseness, and dispositional optimism. Using
      logistic and linear regression analyses, the significant predictors of mental
      health were fewer adverse life events, higher self-esteem, greater perceived
      social support, and less anticipated depressogenic effects when goals were not
      met, while optimism was predicted by fewer adverse life events, higher self
      esteem, lower neuroticism, and higher femininity scores. After discussion of the
      implications of both definitions, it is proposed that both can potentially be
      used as proxies for mental health when more direct well-being measures are
      unavailable. This article reinforces the need for precise conception(s) of mental
      well-being, allowing objective measures to guide future research.

PMID- 20145482
TI  - Psychosocial predictors of military misconduct.
AB  - The objective of this longitudinal study was to determine psychosocial predictors
      of military misconduct in a cohort of Marine Corps war veterans. The study
      included data from 20,746 male Marines who completed a life history questionnaire
      during initial basic training and were subsequently deployed to a combat zone.
      Associations between psychosocial variables, psychiatric diagnoses, and
      subsequent misconduct outcomes were analyzed using Cox proportional hazards
      regression. The strongest predictors of misconduct outcomes (bad conduct
      discharges and military demotions) were psychiatric diagnoses and young age at
      first combat deployment. The results indicate that combat-related psychological
      disorders may manifest in numerous harmful ways, including impulsive, disruptive,
      and antisocial behavior. We recommend that the association between misconduct and
      psychiatric disorders be more explicitly acknowledged in research and treatment
      efforts involving military war veterans and other trauma victims.

PMID- 20145483
TI  - Distress and metacognition in psychosis prone individuals: comparing high
      schizotypy to the at-risk mental state.
AB  - Both schizotypy and at-risk mental states (ARMS: prodromal states) define
      individuals at risk for psychotic symptoms. However, the relationship between the
      2 is unclear. ARMS individuals are, by definition, help-seeking and therefore at
      greater risk. We tested whether high schizotypes and ARMS exist along the same
      continuum by examining maladaptive metacognitions and distress. About 95 healthy
      volunteers (39% male; mean age, 22.8 years) completed the Schizotypal Personality
      Questionnaire, the Launay-Slade Hallucinations Scale, Metacognitions
      Questionnaire (MCQ), and the General Health Questionnaire, and 58 help seeking
      individuals with ARMS status (41% male; mean age, 22.2 years) completed the
      Metacognitions Questionnaire and General Health Questionnaire. With increasing
      expression of schizotypy and hallucinatory proneness healthy volunteers became
      difficult to differentiate from ARMS patients and showed similarities in distress
      and metacognitive abnormalities. Results suggest healthy volunteers who express
      both schizotypal trait and proneness to hallucinations have cognitive processes
      in common with ARMS patients.

PMID- 20145484
TI  - Expressed emotion and health outcomes among Mexican-Americans with schizophrenia
      and their caregiving relatives.
AB  - Past studies have demonstrated a clear relationship between expressed emotion
      (EE) and relapse for individuals with schizophrenia. However, little attention
      has been directed toward exploring whether EE may have negative health
      consequences for caregivers as well. We recruited 60 Mexican-American family
      caregivers of individuals with schizophrenia and examined whether EE predicted
      the health of caregivers and ill relatives approximately 13 months later. For
      caregiving relatives, the EE indices of emotional over-involvement and warmth
      were predictive of worse mental health among caregivers at follow-up. There was
      no association between EE and health outcome among individuals with
      schizophrenia. Our findings suggest that, among Mexican-Americans, family factors
      may be associated with health outcomes among individuals with schizophrenia and
      their caregiving relatives.

PMID- 20145485
TI  - Process and outcome in psychodynamic hospitalization-based treatment for patients
      with a personality disorder.
AB  - This study examined the relationship between the psychotherapeutic process and
      outcome in 44 patients who completed hospitalization-based psychodynamic
      treatment for personality disorders. Using self-report and interview ratings,
      outcome was assessed in terms of symptoms and personality functioning, and the
      psychotherapeutic process in terms of self and object relations, felt safety, and
      reflective functioning. Symptom and process measures were administered at intake,
      every 3 months during treatment, and at 3 and 12 months follow-up. Personality
      measures were collected at intake, the end of treatment, and at 3 and 12 months
      follow-up. Using Piecewise Linear Growth Curve Analysis results showed
      improvement in symptoms, personality functioning, self and object relations and
      felt safety, but not in reflective functioning. Linear changes in self and object
      representation and felt safety, but not in reflective functioning, predicted
      improvement in outcome.

PMID- 20145486
TI  - Meta-analysis of dropout rates in SSRIs versus placebo in randomized clinical
      trials of PTSD.
AB  - Meta-analysis was conducted to examine dropout predictors and differences between
      SSRIs and placebo in randomized clinical trials (RCTs) of PTSD. Studies
      systematically located were SSRI versus placebo double blind RCTs of PTSD DSM
      diagnosis published between 1991 and 2008. Fourteen RCTs (n = 2815) met the
      inclusion criteria with an average duration of 10.8 weeks. Dropout rates were:
      331 of 1111 (29.8%) among placebo arm and 513 of 1704 (30.3%) among SSRI
      participants. Random effects modeling showed that the dropout rates of SSRIs and
      placebo did not differ (OR = 1.05, 95% CI = 0.82-1.34), although favored SSRIs
      among civilian traumas (OR = 2.52, 95% CI = 1.11-5.7). Mixed effects modeling
      showed dropout was predicted by mixed trauma in the placebo arms, and duration
      and mean dose across treatments. With the exception of civilian trauma, SSRIs
      dropout rates were slightly lower than those of placebo. Formulae are available
      to guide the prediction of dropout.

PMID- 20145487
TI  - Effects of functional relaxation and guided imagery on IgE in dust-mite allergic
      adult asthmatics: a randomized, controlled clinical trial.
AB  - Although relaxation and imagination techniques have repeatedly proven their
      effectiveness in asthma, nothing is known about the immunological effects of
      these complementary interventions. Therefore, the aim of this study is to
      investigate the effects of the brief relaxation technique of functional
      relaxation (FR) with guided imagery (GI) on serum IgE in adult patients with dust
      mite allergic asthma in a randomized, controlled trial. Sixty-four patients were
      treated over a 4-week period and assessed at baseline, after treatment and after
      4 months for follow-up. Due to its significant role in the pathophysiology of
      allergic asthma, the serum IgE was employed as outcome measure in this
      investigation. Participation in FR, GI, and FR/GI led to decreases in serum IgE
      (IU/mL) of -54.7 +/- 67.1, -49.5 +/- 93.4, and -28.4 +/- 93.9 compared with an
      increase of 27.7 +/- 43.2 in CI. Our study confirmed a positive and clinically
      relevant effect of FR and GI on total serum IgE levels.

PMID- 20145488
TI  - Associations between attempted suicide, violent life events, depressive symptoms,
      and resilience in adolescents and young adults.
AB  - Were violent/nonviolent traumatic life events and victimization by/witnessing
      violence associates of attempted suicide among depressed adolescents who were
      also less resilient at early adulthood? The present study examined a subset of
      mainly depressed, age- and gender-matched, adolescents derived from a
      representative sample of 2464 students (T1, mean age = 13.7 years) followed up
      after 1 year (T2Q) and reassessed 5 years later (T3, n = 252, mean age = 20.0
      years, 73% participation), with a questionnaire, including the Connor-Davidson
      Resilience Scale and The Kiddie-Schedule for Affective Disorders and
      Schizophrenia-Present and Lifetime version psychiatric interviews, which also
      tapped traumatic life events. Logistic regression analyses revealed that
      attempters were victims, not witnesses of violence, more depressed, and less
      resilient than nonattempters, and that resilience was a moderator of lifetime
      violent events and attempted suicide, even in the presence of antecedent
      depression.

PMID- 20145489
TI  - Social support and quality of life among Latinos with mental illness.
AB  - We examine the degree of social support and quality of life (QOL) among 60
      Latinos with mental illness from a Community Mental Health Center of a large
      metropolitan Midwestern city. Additionally, we assess the relationship of both
      the quality and quantity of social support, and control for demographic factors
      as they all relate to QOL. Latinos had an average network of 3 contacts. Despite
      their small network, participants were satisfied with the quality of support they
      received. Their QOL was mixed, comparable to reports from non-Latinos with mental
      illness, and from the general population. Having better quality of social support
      being male and younger were associated with a higher QOL. Community treatment
      programs for Latinos with mental illness could benefit from focusing on nurturing
      existing networks, fostering social skills, and providing additional forms of
      support for those Latinos in need.

PMID- 20145490
TI  - Mental representations in women with panic disorder: an urban African-American
      sample.
AB  - Psychodynamic theories of panic disorder (PD) suggest an association between PD
      and impairments in mental representations. This study tested this hypothesis by
      comparing mental representations of 25 African-American women recruited from an
      urban primary care clinic with PD with a group of 25 women without PD and matched
      on race, age, marital status, education, and income. Mental representations were
      assessed through spontaneous descriptions of mothers and reliably coded with the
      Qualitative and Structural Dimensions of Object Representations scale (Blatt et
      al., Unpublished manual, 1992). Results essentially supported the hypotheses for
      impaired mental representations (lower benevolence, higher ambivalence, and lower
      conceptual level) for women with PD as compared with women without PD. No
      differences in mental representations were found between women with PD with major
      depression and women with only PD. The findings provide preliminary support for a
      psychodynamic theory of PD in a sample of African-American women.

PMID- 20145491
TI  - Implicit self-stigma in people with mental illness.
AB  - People with mental illness often internalize negative stereotypes, resulting in
      self-stigma and low self-esteem ("People with mental illness are bad and
      therefore I am bad, too"). Despite strong evidence for self-stigma's negative
      impact as assessed by self-report measures, it is unclear whether self-stigma
      operates in an automatic, implicit manner, potentially outside conscious
      awareness and control. We therefore assessed (i) negative implicit attitudes
      toward mental illness and (ii) low implicit self-esteem using 2 Brief Implicit
      Association Tests in 85 people with mental illness. Implicit self-stigma was
      operationalized as the product of both implicit measures. Explicit self-stigma
      and quality of life were assessed by self-report. Greater implicit and explicit
      self-stigma independently predicted lower quality of life after controlling for
      depressive symptoms, diagnosis, and demographic variables. Our results suggest
      that implicit self-stigma is a measurable construct and is associated with
      negative outcomes. Attempts to reduce self-stigma should take implicit processes
      into account.

PMID- 20145492
TI  - Decrements in sustained attention across trials in a continuous performance test:
      associations with social functioning in schizophrenia.
AB  - Deficits in attention are a stable feature of schizophrenia and likely to
      interfere with social function. In this study, we explored whether 2 types of
      attentional dysfunction, increasingly variable and declining reaction times over
      the course of a continuous performance task, were linked to psychosocial
      deficits. Participants were 102 adults with schizophrenia spectrum disorders in
      ongoing outpatient treatment. Concurrent assessments included the Conners'
      Continuous Performance Test II, the Inventory of Interpersonal Problems, and the
      Ways of Coping Questionnaire. Analysis of covariance controlling for global
      performance on the Continuous Performance test suggested that participants with a
      pattern of increasingly variable performance on the task (n = 14) reported being
      more domineering and taken advantage of socially, than those whose performance
      was less variable (n = 88). No differences were found between groups for
      assessments of coping or between participants who showed a declining vs non
      declining reaction time.

PMID- 20145493
TI  - Cognitive functioning in children and adolescents in their first episode of
      psychosis: differences between previous cannabis users and nonusers.
AB  - To investigate the relationship between cognition and prior cannabis use in
      children and adolescents presenting a first episode of psychosis. A total of 107
      patients with first episode of psychosis and 96 healthy controls, aged 9 to 17
      years, were interviewed about their previous substance use and to assess their
      cognitive functions. Patients were assessed while not using cannabis by means of
      a comprehensive neuropsychological battery. They were divided into 2 groups
      depending on the history of prior cannabis use: cannabis users (CU) and cannabis
      nonusers (CNU). Significant differences were found in all areas evaluated between
      the 3 groups. Both CU and CNU patients obtained lower scores than controls on
      verbal learning and memory and working memory. Patients with prior cannabis use
      performed better on some tests of attention (Continuous performance test (CPT)
      number of correct responses, p = 0.002; CPT average reaction time, p < 0.001) and
      executive functions (Trail Making Test, part B (TMT-B) number of mistakes, p <
      0.001; Wisconsin Card Sorting Test (WCST) number of categories completed, p <
      0.001) than CNU patients. CU patients performed better than CNU subjects on some
      cognitive measures. This may indicate lower individual vulnerability for
      psychosis in CU patients in whom cannabis use can be a precipitating factor of
      psychotic episodes.

PMID- 20145494
TI  - Out-of-body experiences and physical body activity and posture: responses from a
      survey conducted in Scotland.
AB  - Although there have been studies of some factors related to the features of out
      of-body experiences (OBEs), the effect of physical body posture and activity has
      not been systematically explored. Over the years research has suggested that OBEs
      are more frequent in states of low physical activity and when the body is supine,
      in agreement with other findings related to alterations in consciousness. Thus,
      we predicted that OBEs would be associated with lying down and little or no
      physical activity, and that these factors would show a higher number of OBE
      features than OBEs in which the person was physically active and/or standing. OBE
      cases were collected through appeals in published sources. Respondents provided a
      description of their only or most recent OBE and filled out a questionnaire about
      OBE features. The findings indicate that OBEs were associated with low physical
      activity and being in a supine position. Those who had experiences under these
      conditions also obtained a higher number of OBE features than those who were
      active and standing at the time of the OBE.

PMID- 20145495
TI  - An alternative interpretation of "the psychotomimetic effects of short-term
      sensory deprivation".

PMID- 20145501
TI  - DNA demethylation in retinal neurocytes contributes to the upregulation of DNA
      repair protein, Ku80.
AB  - Ku80 plays a critical role in DNA double strand breaks repair. However, Ku80 is
      silenced in mature neurocytes. In this study, the mechanism of Ku80 silencing and
      its role in DNA double strand break repair in retinal neurocytes was
      investigated. Our data show that Ku80 expression is activated in primary cultured
      retinal neurocytes after treatment with 5-azacytidine in vitro, whereas
      methylation of -179 bp in Ku80 promoter induces Ku80 silencing in retinal
      neurocytes. Ku80 reactivation in retinal neurocytes by 5-azacytidine enhances DNA
      integrity after treatment with H(2)O(2). Therefore, our data suggest Ku80 might
      be a target for reactivation to increase retinal neuronal DNA repair.

PMID- 20145502
TI  - A penetrating neck injury: trivial trauma with serious consequences.
AB  - Life-threatening complications due to apparently minor penetrating neck injuries
      can occur. We present the case of a 16-year-old boy, who had what initially
      appeared to be a superficial stab wound to his neck. After further evaluation, he
      was found to have major injuries to his larynx and esophagus. This case
      underscores the importance of a careful evaluation after any penetrating neck
      injury, even one that initially appears to be trivial. The pertinent literature
      regarding penetrating neck trauma is reviewed.

PMID- 20145503
TI  - Pneumomediastinum and subcutaneous emphysema in a child with ulcerative colitis.
AB  - We discuss the case of a young adolescent boy with ulcerative colitis who
      developed pneumomediastinum and subcutaneous emphysema in the neck and
      surrounding cervical soft tissues secondary to a probable retroperitoneal
      perforation of the colon. To our knowledge, this is the first reported case of
      this complication in the pediatric literature. Our experience provides insight
      into this unusual complication, how it may present, and its clinical significance
      in young patients with ulcerative colitis. The literature on this complication is
      also discussed.

PMID- 20145504
TI  - Twenty-month-old patient with distal humerus fracture and concomitant septic
      arthritis.
AB  - Septic arthritis is an infection of the joint space that requires prompt
      recognition by physicians. In children, the diagnosis of septic arthritis can
      often be challenging and delayed diagnosis can produce long-term morbidity.
      Posttraumatic septic arthritis is rarely reported and can be an equally
      challenging diagnosis. We present a case of a fully immunized 20-month-old boy
      with Streptococcus pneumoniae posttraumatic septic arthritis without evidence of
      an open fracture.

PMID- 20145505
TI  - A 19-month-old boy with recurrent respiratory distress.
AB  - We present a 19-month-old boy with a history of asthma who presented to the
      pediatric emergency department with noisy breathing and tachypnea partially
      responsive to albuterol. He was discharged to routine care at home. His parents
      brought him back the next day for persistent respiratory distress despite routine
      home albuterol. A check of electrolytes showed a low bicarbonate level.

PMID- 20145506
TI  - Case report: Langerhans cell histiocytosis presenting as massive cervical
      adenopathy and retropharyngeal thickening: importance of chest radiography and
      coordinated airway and anesthetic management.
AB  - OBJECTIVE: To demonstrate the importance of chest radiography and special
      anesthetic management in children with massive cervical adenopathy. METHOD: Case
      report of an 8-month-old infant who presented to the emergency department with
      fever, drooling, and massive cervical and mediastinal adenopathy. Safe anesthetic
      management allowed for cervical lymph node biopsy, which showed Langerhans cell
      histiocytosis. RESULTS: Chest imaging and special anesthetic techniques
      (intravenous anesthesia and positioning in the lateral decubitus position) should
      be considered for children with massive cervical and mediastinal adenopathy.
      CONCLUSIONS: Interdisciplinary airway, radiographic, and anesthetic management is
      recommended for children who present with massive and cervical and mediastinal
      adenopathy.

PMID- 20145507
TI  - Orbital trauma, bradycardia, and vomiting: trapdoor fracture and the oculocardiac
      reflex: a case report.
AB  - The presentation of vomiting and bradycardia after closed head trauma should
      invariably prompt concern for significant intracranial injury, yet other less
      common causes for the clinical picture do exist. This case reports one such
      scenario in which fracture to the patient's inferior orbital wall resulted in the
      rare though potentially life-threatening oculocardiac reflex, a vagally mediated
      phenomenon with possible respiratory, cardiovascular, and gastric motility
      effects.

PMID- 20145508
TI  - Salicylic acid ingestion leading to esophageal stricture.
AB  - Accidental ingestion of caustic substances (acid and alkali) occurs more
      frequently in children than in adults. The subsequent injury varies from minimal
      to severe, with perforation and even death as potential complications. Several
      factors have been shown to mediate the severity of injury, including the pH,
      concentration and physical state of the ingested substance, tissue contact time,
      and quantity (volume) of the ingested material. Liquids with a pH of less than 2
      (acidic) or a pH of greater than 12 (alkali) are considered to be extremely
      corrosive and hold the greatest risk for injury. Esophageal injury after caustic
      ingestion is endoscopically graded with a score of 0 for no injury to IIIb for
      significant circumferential injury with ulcers and necrosis. Ingestion of either
      a strong alkali or acid has been documented to result in esophageal necrosis and
      ulcers (grade IIIb). Alkali ingestions occur more frequently because of their
      presence in daily life (detergents, degreasers) and therefore have more reports
      of injury. Despite more than 8200 documented cases of topical salicylic acid
      ingestions annually in US children younger than 19 years, there are no reported
      cases of salicylic acid resulting in gastrointestinal pathology. We report 2
      cases of salicylic acid ingestion resulting in esophageal strictures. Both
      patients had more significant injury than anticipated given their initial
      clinical presentations. Given our recent experience, we recommend close follow-up
      and evaluation for strictures in patients with exposure to salicylic acid.

PMID- 20145509
TI  - A 7-year-old boy with acute onset of breathing difficulty.
AB  - Group A streptococcus (GAS) is a major bacterial pathogen affecting children
      globally. Approximately 15% of school-age children experience a symptomatic
      episode of GAS culture-positive pharyngitis each year. Although the incidence of
      invasive GAS disease under these circumstances is low (0.5%-2%), an increasing
      number of invasive GAS cases have been reported over the last 2 decades. This
      report describes a 7-year-old boy who, after being treated for GAS pharyngitis,
      developed a fatal streptococcal toxic shock syndrome.

PMID- 20145510
TI  - Common pediatric fractures treated with minimal intervention.
AB  - The unlikely event of long-term complications in some pediatric fractures, such
      as midclavicular fractures, has allowed for management of these injuries with
      interventions that support the injured extremity rather than immobilize it while
      healing occurs. However, there is currently a growing body of evidence that
      advocates for this approach for some of the most frequently encountered pediatric
      fractures also at very low risk of future problems but, in contrast, have
      conventionally been managed with orthopedic consultation and rigid casting for
      several weeks. Therefore, this article will review the evidence that recommends
      that management of some of the most common upper and lower pediatric extremity
      fractures be treated with minimal interventions, such as removable splints and
      follow-up with a primary care provider.

PMID- 20145512
TI  - ECGs in the ED.

PMID- 20145513
TI  - Pediatric emergency medicine: legal briefs.

PMID- 20145514
TI  - Sunday's child? A memoir by Leslie Baruch Brent.

PMID- 20145515
TI  - Mesenchymal stem-cell immunosuppressive capabilities: therapeutic implications in
      islet transplantation.
AB  - Mesenchymal stem cells (MSCs) are known to be capable of suppressing immune
      responses and offer therapeutic potential for achieving transplantation
      tolerance. This review will discuss the impacts of MSCs on transplant immunity
      and focus on the potential role of MSCs in protecting islet grafts from both
      rejection and autoimmune attack.

PMID- 20145516
TI  - Preserving the gut: give it what it wants.

PMID- 20145517
TI  - Proteasome inhibitor-based primary therapy for antibody-mediated renal allograft
      rejection.
AB  - BACKGROUND: Rapid and complete elimination of donor-specific anti-human leukocyte
      antigen antibodies (DSA) during antibody-mediated rejection (AMR) is rarely
      achieved with traditional antihumoral therapies. Proteasome inhibitor-based
      therapy has been shown to effectively treat refractory AMR, but its use as a
      primary therapy for AMR has not been presented. Our initial experience with
      proteasome inhibition as a first-line therapy for AMR is presented. METHODS:
      Adult kidney transplant recipients with AMR, diagnosed by Banff criteria,
      received a bortezomib-based regimen as the primary therapy. Bortezomib therapy
      was administered per package insert with plasmapheresis performed immediately
      before each bortezomib dose, and a single rituximab dose (375 mg/m2) given with
      the first bortezomib dose. DSA were quantitated using single-antigen beads on a
      Luminex platform. RESULTS: Two patients underwent bortezomib-based therapy for
      acute AMR occurring within the first 2 weeks after transplantation. High DSA
      levels and positive C4d staining of peritubular or glomerular capillaries were
      present at the time of diagnosis. Both patients experienced prompt AMR reversal
      and elimination of detectable DSA within 14 days of bortezomib-based therapy.
      Renal function remains excellent with normal urinary protein excretion at 5 and 6
      months after AMR diagnosis. One patient experienced a repeated elevation of DSA
      (including two new human leukocyte antigen specificities) 2 months after initial
      bortezomib therapy, but without C4d deposition or histologic evidence of AMR.
      Retreatment with bortezomib provided prompt, complete, and durable DSA
      elimination. CONCLUSIONS: Proteasome inhibitor-based combination therapy provides
      a potential means for rapid DSA elimination in early acute AMR in renal
      transplant recipients.

PMID- 20145518
TI  - Improved intestinal preservation using an intraluminal macromolecular solution:
      evidence from a rat model.
AB  - BACKGROUND: Intestinal preservation injury consists of progressive submucosal
      edema, with fluid originating both from the lumen and the interstitium. Although
      vascular flushing aims to control electrolyte shifts in the tissue, the lumen is
      not addressed, and luminal water and electrolytes enter the tissue during
      ischemia. Because macromolecular solutions may retain water and electrolytes
      intraluminally, we investigated whether these solutions administered
      intraluminally may alleviate preservation injury. METHODS: Sprague-Dawley rat
      intestines were perfused with University of Wisconsin solution. After excision of
      the intestines, we intraluminally introduced solutions containing polyethylene
      glycol 3350 with high (125 mEq) or low (65 mEq) sodium before cold preservation.
      Controls underwent only vascular flush. After 8, 14, or 20 hr of cold storage,
      the intestines were analyzed for extent of tissue injury, water retention, brush
      border maltase, and tight junction proteins zonula occludens-1 and claudin-3.
      RESULTS: Intraluminal composition changed over time, indicating sodium absorption
      and potassium secretion. After 8 and 14 hr of cold storage, intestines from the
      low-sodium group had the best morphology and least edema, followed by the
      controls. Maltase activity slightly decreased in all groups over time and was not
      affected by the intraluminal polyethylene glycol solutions. Various degrees of
      delocalization and degradation of zonula occludens-1 and claudin-3 were recorded
      within the tight junctions, with the most significant effects in intestines from
      the high-sodium group. CONCLUSIONS: Intraluminal macromolecular solutions may
      modulate the preservation injury in University of Wisconsin- perfused intestines.
      Low-sodium solutions administered immediately before preservation may improve
      preservation injury, but high-sodium solutions may be detrimental.

PMID- 20145520
TI  - A suppressive effect of cyclosporine A on replication and noncoding control
      region activation of polyomavirus BK virus.
AB  - BACKGROUND: The effect of cyclosporine A (CsA) on polyomavirus BK virus (BKV)
      replication remains unclear. The aim of this in vitro study was to investigate
      the effect of CsA on BKV replication in human uroepithelial cells. METHODS: After
      infection of a human renal proximal tubular cell line, HK-2 with BKV, BKV viral
      load in the presence of CsA was assessed by real-time polymerase chain reaction.
      The BKV large T-antigen (LTag) expression was measured by Western blot analysis.
      The BKV early promoter activity was determined by measuring luciferase activity
      of the BKV noncoding control region luciferase reporter. The BKV LTag expression
      in a human bladder carcinoma cell line, T24, was assessed by immunofluorescence.
      RESULTS: The results demonstrated that the increased levels of BKV LTag and viral
      protein 1 transcripts measured by real-time polymerase chain reaction were
      suppressed by CsA in a dose-dependent manner (0.5-4 microg/mL). Western blot
      analysis also showed that CsA inhibited BKV LTag expression. In addition, the
      activity of the BKV early promoter, which was enhanced by BKV LTag
      overexpression, was abrogated by CsA. Finally, the suppressive effect of CsA on
      BKV replication was also shown in T24 cells as CsA reduced immunofluorescent
      staining of BKV LTag in these cells. CONCLUSION: This in vitro study indicates
      that CsA suppresses BKV replication in human proximal renal tubular cells and
      uroepithelial cells of the urinary bladder and inhibits the BKV-LTag-regulated
      increase in early promoter activity.

PMID- 20145521
TI  - Plasma nitrite and nitrate levels as a noninvasive marker of pathology after
      human small bowel transplantation.
AB  - INTRODUCTION: Small bowel transplantation provides a potentially life-saving
      treatment of severe intestinal failure. Lack of a noninvasive marker of disease
      makes diagnosis of rejection dependent on frequent endoscopy and biopsy. We
      hypothesized that increased plasma nitrite and nitrate (NOx) levels measured
      after small bowel transplant would be associated with abnormal final pathology.
      METHODS: We measured total plasma NOx levels (the stable end products of the L
      arginine/nitric oxide biosynthetic pathway) in 120 prospectively collected
      samples taken from 27 patients after small bowel transplantation. We used
      immunohistochemistry to detect inducible nitric oxide synthetase expression in 19
      tissue biopsies from 9 patients. RESULTS: We found NOx concentrations to be
      statistically different between pathologic categories (e.g., normal, mild,
      moderate, and severe rejections, nonspecific enteritis), although there was
      sufficient overlap to prompt caution clinically. After establishing from the
      dataset a "normal" plasma NOx level of 50 microM, we found that combined
      assessment of plasma NOx levels and clinical suspicion of pathology could
      accurately predict which patients were histologically normal and those requiring
      further evaluation with endoscopy and biopsy. CONCLUSIONS: We conclude that serum
      NOx levels are significantly associated with small bowel pathology after
      transplant, although not specifically enough with rejection to be relied on for
      clinical discrimination.

PMID- 20145519
TI  - Inhibition of inducible nitric oxide synthase prevents mitochondrial damage and
      improves survival of steatotic partial liver grafts.
AB  - BACKGROUND: Steatotic liver grafts are excluded for partial liver transplantation
      because of increased risk of primary nonfunction. Mechanisms underlying the
      failure of fatty partial liver grafts (FPG) remain unknown. This study
      investigated whether inducible nitric oxide synthase (iNOS) plays a role in
      failure of FPG. METHODS: Fatty livers were induced by feeding rats a high-fat
      high-fructose diet for 2 weeks. Hepatic triglyceride was approximately 9-fold
      higher in rats fed the high-fat high-fructose diet than those fed a low-fat low
      fructose diet. Lean and fatty liver explants were reduced in size ex vivo to
      approximately one third, stored in the University of Wisconsin cold storage
      solution for 2 hr, and implanted. RESULTS: Posttransplantational hepatic iNOS
      expression and reactive nitrogen species (RNS) formation (nitrite and nitrate
      levels and 3-nitrotyrosine adducts) increased more profoundly in FPG than in lean
      partial grafts (LPG). Serum alanine aminotransferase and bilirubin were 2- and
      5.5-fold higher after transplantation of FPG than LPG. 5-Bromo-2'-deoxyuridine
      incorporation was 25% in LPG but only 5% in FPG, and graft weight increased by
      64% in LPG while remaining unchanged in FPG. All rats that received FPG died,
      whereas all those receiving LPG survived. N-(1-naphtyl)ethylendiamine
      dihydrochloride (5 microM), a specific iNOS inhibitor, largely blunted the
      production of RNS, prevented the increase of alanine aminotransferase and
      bilirubin, restored liver regeneration, and improved survival of FPG.
      Mitochondrial cytochrome c oxidase-IV, ATP synthase-beta, and NADH dehydrogenase
      3 decreased markedly in FPG, and these effects were blocked by N-(1
      naphtyl)ethylendiamine dihydrochloride. CONCLUSION: Thus, hepatic steatosis
      causes failure of partial liver grafts, most likely by increasing RNS that leads
      to mitochondrial damage and dysfunction.

PMID- 20145522
TI  - Compartmental localization and clinical relevance of MICA antibodies after renal
      transplantation.
AB  - BACKGROUND: Antibodies (Ab) responses to major and minor human leukocyte antigen
      loci may impact graft survival after organ transplantation. METHODS: A ProtoArray
      platform was used to study 37 serum samples from 15 renal transplant patients
      with (n=10) and without (n=5) acute rejection (AR) and seven normal controls, and
      the clinical relevance of major histocompatibility complex class I chain-related
      gene-A (MICA)-Ab measurements were investigated. Biopsy immunohistochemistry was
      conducted for localization of the MICA antigen. RESULTS: De novo MICA-Ab were
      detected in 11 of the 15 transplant patients in this study, irrespective of
      interval acute graft rejection. Mean MICA-Ab signal intensity was higher in
      transplant patients with C4d+AR (121.4) versus C4d-AR (4.3), correlated with
      donor-specific Ab to human leukocyte antigens (r=0.66, P=0.0078), was not
      elevated in cellular rejections, and correlated with decline in graft function
      over the subsequent year (r=0.73, P=0.0022). Integrative genomics accurately
      predicted localization of the MICA antigen to the glomerulus in the normal kidney
      (Li et al. Proc Natl Acad Sci USA 2009; 106: 4148), because this was confirmed
      subsequently by immunohistochemistry. CONCLUSIONS: Integrative genomics analysis
      of ProtoArray data is a powerful tool to ascertain de novo antibody responses
      after renal transplantation and to accurately predict the anatomical location of
      the target renal antigens. This proof-of-concept study on MICA measurements by
      ProtoArray demonstrates that antibody responses modulated to MICA after
      transplantation in patients, irrespective of graft rejection, may be high at the
      time of humoral rejection and may not be elevated in cellular rejection.
      Understanding that MICA is preferentially localized to the glomerulus may explain
      both immunoregulatory and pathogenic roles for MICA after transplantation.

PMID- 20145523
TI  - Preemptive versus sequential prophylactic-preemptive treatment regimens for
      cytomegalovirus in renal transplantation: comparison of treatment failure and
      antiviral resistance.
AB  - BACKGROUND: Cytomegalovirus (CMV) infections after transplantation are commonly
      treated using a prophylactic or preemptive regimen with (val)ganciclovir. It
      remains unclear, which approach is most effective in preventing CMV disease in
      D+R- patients. The aim of this retrospective study was to compare the treatment
      response and antiviral resistance in CMV infections between two treatment
      regimens in D+R- renal transplant recipients. METHODS: Before 2006, a preemptive
      treatment regimen with valganciclovir was applied (42 patients). From 2006
      onwards, patients first received prophylaxis with valganciclovir for 90 days,
      followed by a preemptive regimen (29 patients). CMV infections were monitored by
      regular determination of the CMV DNA load in plasma. Patient charts were reviewed
      for antiviral treatment data, and resistance was analyzed by nucleotide sequence
      analysis of the UL97 and UL54 genes in CMV DNA-positive samples. RESULTS:
      Treatment failure, defined as a CMV DNA load more than or equal to 1000 copies/mL
      after at least 2 weeks of treatment, occurred less frequently in the prophylaxis
      cohort than in the preemptive cohort (14% vs. 71%, P<0.001). No CMV end-organ
      disease occurred in either cohort. Resistant viral isolates were found during
      treatment in one patient in the prophylaxis cohort versus in three patients in
      the preemptive group. All CMV infections with resistant virus were cleared
      without switch of (val)ganciclovir treatment. CONCLUSIONS: Treatment failure of
      CMV infections occurred less frequently in D+R- renal transplant patients on a
      sequential prophylaxis-preemptive regimen than in patients on a purely preemptive
      regimen. Antiviral resistance was observed infrequently and apparently played a
      minor role in treatment failure.

PMID- 20145524
TI  - Insulin resistance indexes in renal transplant recipients maintained on
      tacrolimus immunosuppression.
AB  - BACKGROUND: Insulin resistance is common posttransplantation and contributes to
      both new onset diabetes after transplantation and the metabolic syndrome. Insulin
      resistance indexes have never been validated in transplant recipients on
      tacrolimus compared with cyclosporine, although it is more diabetogenic. We aimed
      to assess these indexes in renal transplant recipients on tacrolimus as primary
      immunosuppressant. METHODS: Retrospective analysis of 76 frequently sampled,
      intravenous glucose tolerance tests (for insulin sensitivity) in 38 nondiabetic
      renal transplant recipients on tacrolimus-centered immunosuppression. Indexes
      tested were fasting glucose/insulin ratio, homeostasis model assessment (HOMA)
      index, 1/HOMA, log (HOMA), quantitative insulin sensitivity check index, and the
      McAuley's index. Indexes were also compared against waist/hip ratio and C
      reactive protein (CRP). Multivariate linear regression analysis was performed to
      determine independent variables predictive for insulin resistance. RESULTS:
      Insulin sensitivity successfully correlated with all indexes: fasting
      glucose/insulin ratio (r=0.246, P=0.033), HOMA index (r=-0.240, P=0.038), 1/HOMA
      (r=0.282, P=0.014), log (HOMA) (r=-0.316, P=0.006), quantitative insulin
      sensitivity check index (r=0.320, P=0.005), and McAuley's index (r=0.323,
      P=0.005). McAuley's index also correlated strongest with waist/hip ratio (r=
      0.425, P<0.001). All indexes failed to correlate with CRP. Variables
      independently associated with insulin sensitivity were HbA1c (r=0.189, P=0.019),
      pulse pressure (r=0.146, P=0.021), and CRP (r=0.210, P=0.010). CONCLUSIONS:
      Insulin resistance indexes are valid in transplant recipients taking tacrolimus,
      with McAuley's index the strongest surrogate.

PMID- 20145525
TI  - Patterns of chronic injury in pediatric renal allografts.
AB  - BACKGROUND: In pediatric recipients, the pathophysiology of chronic renal
      allograft injury is poorly understood. METHODS: We studied the evolution and
      determinants of tubulointerstitial, vascular, and glomerular injury in 240
      pediatric protocol renal allograft biopsies during the first 5 years
      posttransplant. RESULTS: Chronic tubulointerstitial injury (ci, ct) developed
      predominantly during the first 12 months posttransplant, whereas chronic vascular
      damage (cv, and arteriolar hyalinosis [ah]) and global glomerulosclerosis (gs)
      became increasingly prevalent at 25 to 36 months and beyond. Chronic interstitial
      lesions were associated with acute rejection and borderline histology (odds ratio
      [OR] 2.3, P<0.04), recipient body surface area less than 1.0 m2 (OR 3.6, P<0.05),
      and obesity (OR 2.0, P<0.03). Determinants of ct were acute rejection (OR 2.6,
      P=0.02) and acute tubular necrosis (OR 2.8, P<0.04). Vascular fibrous intimal
      thickening and ah were associated with donor hypertension (OR 3.6, P=0.001) and
      recipient body surface area less than 1.0 m (OR 2.6, P=0.02), respectively. The
      severity of ah correlated with the incidence of gs (r=0.32, P<0.0001), with 7.8%
      gs for ah0, 14.3% gs for ah1, 60.0% gs for ah2, and 95.5% gs for ah3 (median
      values). Antibody induction conferred protection from ci (OR 0.31, P=0.008), ct
      (OR 0.33, P=0.002), and ah (OR 0.12, P<0.001) progression. CONCLUSIONS: By 5
      years posttransplant, pediatric renal allografts manifest a substantial burden of
      tubulointerstitial and microvascular injury. These lesions are associated with
      donor hypertension, acute inflammation, renal hypoperfusion, obesity, and
      calcineurin inhibitor toxicity. The pervasiveness and rapid progression of
      microvascular lesions at 25 to 36 months suggest that attempts at reducing
      calcineurin inhibitor exposure should be made before two years posttransplant.

PMID- 20145526
TI  - Troponin I is a predictor of acute cardiac events in the immediate postoperative
      renal transplant period.
AB  - BACKGROUND: Patients on the renal transplant waiting list and renal transplant
      recipients have an increased risk of premature cardiovascular (CV) disease and
      death. METHODS: We performed a prospective observational study in 331 kidney or
      kidney-pancreas transplant recipients to test whether Troponin I (TnI),
      determined at time of engraftment, can help to identify patients at risk for a
      major adverse cardiac event (MACE) in the immediate postoperative period.
      Logistic regression analysis was used to test if pretransplant TnI is a predictor
      of MACE within 3 months after transplantation. RESULTS: Eleven patients (3.3%)
      developed a MACE during the first 2 weeks after transplantation. In patients with
      a CV history (23.6%), the incidence of MACE increased to 13.4%. In univariate
      analysis, age (odds ratio [OR] 1.062, P=0.04), TnI (OR 1.12, P=0.0042), HbA1c (OR
      1.879, P=0.0076), and CV history (absent vs. present OR 0.027, P=0.0006) were
      associated with MACE. TnI remained an independent predictor after adjusting for
      every other significant variable. When we restricted the analysis to patients
      with a CV history, TnI was the only statistically significant variable associated
      with MACE. CONCLUSION: Elevated TnI, immediately pretransplant, is an independent
      predictor of MACE in the immediate posttransplant period, particularly in
      patients with CV history.

PMID- 20145527
TI  - Comparison of rival metabolic syndrome classifications against pathophysiological
      markers in renal transplant recipients.
AB  - BACKGROUND: Metabolic syndrome posttransplantation is associated with adverse
      outcomes. Diagnostic controversy exists, with adult treatment panel (ATP) III and
      International Diabetes Federation (IDF) classifications differing in prerequisite
      requirement of central obesity. In addition, correlation between classifications
      and putative pathophysiological mechanisms posttransplantation are lacking and
      may be obscured by immunosuppressants. We compared the two classifications
      against insulin resistance, subclinical inflammation, and central obesity in
      renal transplant recipients. METHODS: Ninety-six sets of metabolic investigations
      were analyzed in a cohort of 58 nondiabetic renal transplant recipients.
      Mathematical model analysis of the frequently sampled, intravenous glucose
      tolerance test was performed to determine insulin sensitivity (10(-5)min(
      1)/mU/mL). We used waist/hip ratio as a surrogate for central obesity and C
      reactive protein (mg/L) for subclinical inflammation, respectively.
      Clinical/biochemical parameters were also assessed at each metabolic
      investigation. RESULTS: Fifty-nine percent of the study cohort was classed with
      metabolic syndrome using ATP III criteria, but only 43% using IDF criteria. IDF
      classified recipients were more likely to have insulin resistance (3.7 vs. 4.9,
      P=0.034), raised waist/hip ratio (0.96 vs. 0.88, P<0.001), and elevated C
      reactive protein (7.2 vs. 2.9, P=0.004) than those without the syndrome. Using
      ATP III criteria, there was a significant association with waist/hip ratio alone
      (syndrome vs. no syndrome, 0.95 vs. 0.86, P<0.001). Recipients with IDF
      classified metabolic syndrome had significantly lower estimated glomerular
      filtration rate (mL/min) compared with those without (61.8 vs. 73.6, P=0.015).
      CONCLUSION: The IDF-classified metabolic syndrome is superior to ATP III for
      association with pathophysiological mechanisms posttransplantation.

PMID- 20145528
TI  - Influence of immunosuppressive therapy on the natural history of genotype 3
      hepatitis-E virus infection after organ transplantation.
AB  - BACKGROUND: Hepatitis-E virus (HEV) infection can be responsible for chronic
      hepatitis in solid-organ transplant patients. METHODS: We identified 33 cases of
      autochthonous acute HEV infection in solid-organ transplant patients. RESULTS:
      Among 27 HEV-positive patients, who had a follow-up of more than 6 months, 16
      (59.25%) evolved to chronic HEV infection, defined by persisting elevated liver
      enzyme levels and positive serum HEV RNA 6 months after diagnosis. Serial liver
      biopsies showed progression in liver activity and liver fibrosis. Three patients
      developed liver cirrhosis. The proportion of patients receiving tacrolimus
      compared with cyclosporine A was significantly higher in patients who evolved to
      chronic disease. Immunosuppressive therapy was reduced in patients with chronic
      hepatitis; however, those who had a dramatic decrease in tacrolimus trough levels
      were more likely to clear the virus. Four chronic liver transplant patients were
      cleared off the virus at 14, 16, 22, and 23 months after diagnosis. At last
      follow-up, their tacrolimus trough levels and daily steroid doses were
      significantly lower than those who remained viremic. These four patients had
      lower liver-enzyme levels and lower activity scores on liver biopsies, and their
      peripheral blood CD3- and CD4-positive cell counts were also significantly
      higher. CONCLUSIONS: The rate of chronic HEV-related hepatitis is approximately
      60% in solid-organ transplant patients. When possible, the reduction of
      immunosuppressive drugs targeting T cells should be considered as a first-line
      therapeutic option.

PMID- 20145529
TI  - Supplemental islet infusions restore insulin independence after graft dysfunction
      in islet transplant recipients.
AB  - BACKGROUND: The ability of supplemental islet infusions (SII) to restore insulin
      independence in islet transplant recipients with graft dysfunction has been
      attributed to the coadministration of exenatide. However, improving islet
      transplant outcomes could explain the success of SII. We aimed to determine the
      effect on islet graft function and insulin independence of SII using these new
      protocols, without the use of exenatide. METHODS: Seventeen islet transplant
      recipients underwent SIIs after developing graft dysfunction requiring insulin
      use. For induction therapy, four subjects received daclizumab induction therapy,
      whereas 13 subjects received thymoglobulin and etanercept. Maintenance
      immunosuppression consisted of sirolimus+tacrolimus or tacrolimus+cellcept.
      RESULTS: SII was performed 49.3+/-4.8 months (mean+/-SEM) after the preceding
      islet transplant. Subjects received significantly lower islet mass with their SII
      compared with initial transplant(s) (6076+/-492 vs. 9071+/-796 IEQ/kg; P=0.003).
      Fifteen of the 17 subjects (88.2%) became insulin independent 2.4+/-0.5 months
      after SII. Insulin-independent duration after SII exceeded that of the initial
      transplant(s) (24.8+/-2.2 vs. 14.2+/-2.6 months by Kaplan-Meier analysis,
      P=0.009). Subjects show improved glycemic control after SII (HbA1c 7.0%+/-0.2%
      pre-SII vs. 6.1%+/-0.2% post-SII, P=0.005) and did not become immunosensitized.
      CONCLUSION: Using current protocols, SII in the absence of exenatide results in
      impressive insulin-independence rates and the durability of insulin independence
      seems to be promising. However, a beneficial effect of exenatide should not be
      discounted until tested in randomized controlled studies.

PMID- 20145530
TI  - Quantification of circulating regulatory T cells by flow cytometry in kidney
      transplant patients after basiliximab induction therapy.

PMID- 20145531
TI  - Bullous pemphigoid associated with acute renal allograft rejection.

PMID- 20145532
TI  - Rapidly progressive lethal infection with novel influenza A (H1N1) 2009 virus in
      a kidney recipient: a cautionary tale.

PMID- 20145533
TI  - Free-floating collagen fibers in interstitial mycosis fungoides.
AB  - We present a case of interstitial mycosis fungoides showing pseudodovascular
      clefts with "free-floating" collagen fibers surrounded by neoplastic T
      lymphocytes. Such a finding further expands the histopathologic spectrum of
      mycosis fungoides and could be taken into account in its differential diagnosis
      from granuloma annulare, inflammatory morphea, and interstitial granulomatous
      drug reaction.

PMID- 20145534
TI  - Basal cell carcinoma-associated paratumoral follicular and epidermal hyperplasia.
AB  - Reactive epithelial hyperplasia is a well-known phenomenon which occurs adjacent
      to certain neoplasms such as cutaneous fibrous histiocytoma, granular cell tumor,
      Spitz nevus, and melanoma. We report 46 cases of paratumoral follicular and
      epidermal hyperplasia associated with basal cell carcinoma (BCC). This reactive
      process associated with BCC has certain characteristic features. It is focal,
      superficial, and predominantly folliculocentric. It may resemble other tumors
      such as squamous cell carcinoma and may appear in sections where BCC is absent.
      The recognition of this entity may help dermatopathologists avoid misdiagnosing
      this process as a tumor and can suggest further search (section through the block
      or rebiopsy) when this reactive phenomenon is seen in sections without the
      associated BCC.

PMID- 20145535
TI  - Squamous cell carcinoma with osteoclast-like giant cells: 2 cases misdiagnosed as
      atypical fibroxanthoma.

PMID- 20145536
TI  - Spitz nevus: an evolving clinicopathologic concept.

PMID- 20145537
TI  - Celecoxib activates Stat5 and restores or increases the expression of growth
      hormone-regulated genes in hepatocarcinogenesis.
AB  - We have previously evaluated the chemopreventive effect of celecoxib on
      preneoplastic lesions in rat liver. However, though the effects of celecoxib have
      been tested in a variety of carcinomas, there has not been a study on the
      modulation of gene expression in response to this drug. Here, we evaluated the
      effect of celecoxib on the gene expression profile associated with
      hepatocarcinogenesis. Male Sprague-Dawley rats underwent the modified resistant
      hepatocyte model and were fed a diet containing 1500 ppm of celecoxib. Gene
      expression profiles were evaluated using DNA microarrays and further validations
      were performed using quantitative PCR, western blotting and immunohistochemical
      staining. Celecoxib modulated the expression of 46 genes, and those regulated by
      growth hormone were selected for further analysis. Celecoxib significantly
      upregulated the expression of the Cyp2b1/2, Cyp3a1, and alpha2-urinary globulin
      (alpha2uG) genes and restored the expression of Cyp2b3 to normal. The protein
      expression of Cyp2b1/2 was increased, but the expressions of Cyp3a1 and alpha2uG
      were only restored to normal levels. The increased Cyp2b1/2 expression in
      response to celecoxib was mainly confined to preneoplastic lesions. A search for
      the upstream mediator of these genetic alterations found that carcinogenesis
      inactivated by 87% the signal transducer and activator of transcription 5
      (Stat5), a transcription factor that is activated by growth hormone signaling,
      but celecoxib treatment restored its activation. In conclusion, these results
      suggest that celecoxib exerts anticancer effects on altered hepatic cells by
      restoring mRNA and the protein expression levels of specific genes, in part
      through the reactivation of Stat5.

PMID- 20145538
TI  - Tranilast inhibits cell proliferation and migration and promotes apoptosis in
      murine breast cancer.
AB  - The malignant transformation of breast epithelium involves a number of cellular
      pathways, including those dependent on signaling from TGF beta. Tranilast [N-(3,
      4-dimethoxycinnamonyl)-anthranilic acid] is a drug that is used in Japan to
      control allergic disorders in patients, and its mechanism of action involves TGF
      beta. In view of the multiple roles of TGF beta in tumor progression, we
      hypothesized in this study that tranilast impacts cell proliferation, apoptosis,
      and migration. Using the mouse breast cancer cell line 4T1, our studies showed
      that tranilast increases AKT1 phosphorylation and decreases ERK1/2
      phosphorylation. Alterations in the cell cycle mediators' cyclin D1, p27, cyclin
      A, pRB, cyclin B, and Cdc2 were observed after exposure to tranilast, favoring
      cell arrest beyond the G1/S phase. Tranilast reduced tumor cell proliferation
      even when it was amplified by exogenous TGF beta. TGF beta-neutralizing antibody
      did not cause a significant decrease in cell proliferation. Tranilast treatment
      upregulates p53, induces PARP cleavage in vitro, consistent with a promotion of
      tumor cell apoptosis. TGF beta-neutralizing antibody downregulates endoglin and
      matrix metalloproteinases (MMP)-9 levels in vitro indicating that the tranilast
      effect is mediated through TGF beta modulation. Tranilast treatment results in
      the inhibition of cell migration and invasion. Western blot analysis of tumor
      lysates from tranilast-treated mice shows decreased levels of TGF beta1,
      endoglin, and significantly higher levels of p53 and cleaved PARP. Cleaved
      caspase 3 expression is significantly elevated in tranilast-treated mouse breast
      tumors. To conclude, tranilast induces cellular and molecular changes in murine
      breast cancer that can be exploited in preclinical therapeutic trials.

PMID- 20145539
TI  - Knowledge and beliefs of Jordanians toward colorectal cancer screening.
AB  - BACKGROUND: Colorectal cancer is a significant health problem; it is the most
      common malignancy of the gastrointestinal tract. Colorectal cancer is closely
      related to the clinical and pathological stage of the disease at diagnosis, which
      can be detected early through screening tests. OBJECTIVE: This descriptive cross
      sectional study was conducted to investigate the knowledge and beliefs of
      Jordanians toward colorectal cancer (CRC) screening using the Health Belief
      Model. METHODS: One hundred sixty participants, 50 years and older, were
      identified in the outpatient clinics at the 2 largest Jordanian hospitals located
      in the north of the country; the King Abdullah University Hospital and the
      Princess Basma Hospital. RESULTS: Data analyses revealed that most participants
      are not well informed about CRC and screening. Less than half perceived
      themselves as susceptible to developing CRC. Half comprehended the seriousness of
      CRC, the majority understood the benefits of CRC screening, and one-third
      realized the barriers of CRC screening. Moreover, most understood the importance
      of preventative medicine and was highly motivated. CONCLUSION: Most Jordanians
      treated at outpatient clinics comprehend the benefits from CRC screening,
      understand the seriousness of CRC, and perceive barriers, and more than half of
      the patients perceive the general health motivation beliefs and outcomes.
      IMPLICATION FOR PRACTICE: The healthcare system and the decision makers must
      develop strategies to increase the general population's awareness about CRC and
      the accompanying screening tests.

PMID- 20145540
TI  - Video capsule endoscopy of the small bowel.
AB  - PURPOSE OF REVIEW: It is now over 8 years since small bowel capsule endoscopy
      (SBCE) was first introduced to the gastrointestinal community. The original
      capsule (Given Imaging, YoKneam, Israel) - a disposable 26 x 11 mm video capsule
      containing its own optical dome, light source, batteries, transmitter and antenna
      - is swallowed with water after a 12 h fast. The capsule is propelled via
      peristalsis through the gastrointestinal tract and is excreted naturally. We will
      review all recent work concerning SBCE. RECENT FINDINGS: At present there are
      three other SBCEs in the market. SBCE has become a first-line tool to detect
      abnormalities in the small bowel, as all other imaging technologies are rather
      ineffective, or very tedious.Indications for SBCE include obscure
      gastrointestinal bleeding, suspected small bowel tumor, suspected Crohn's
      disease, surveillance of inherited polyposis syndromes, drug-induced small bowel
      injury or any abnormal small bowel imaging and new ones are emerging like small
      bowel motility. Since most of the articles in the literature relate to the
      PillCam small bowel capsule the data presented will refer mainly to this capsule
      endoscopy. SUMMARY: SBCE has shed new light into our knowledge of the small
      bowel, paving the way for new modalities to come.

PMID- 20145541
TI  - The risk of oesophageal cancer is not affected by a diagnosis of breast cancer.
AB  - Oesophageal adenocarcinoma (OAC) is less common and develops at a later age in
      women compared with men. Endogenous oestrogen may therefore protect against OAC
      development. A cohort of women with breast cancer, a tumour commonly treated with
      oestrogen antagonists, was examined to identify the subsequent risk of developing
      OAC. Earlier studies have implicated radiotherapy in increasing oesophageal
      cancer (OC) risk among women with breast cancer. West Midlands Cancer
      Intelligence Unit data recording cancer diagnosis and treatment information was
      examined to identify patients with a first malignant primary breast cancer during
      1977-2004. Patients were followed until diagnosis of a second primary cancer,
      death or end of the time period examined. Age-adjusted and period-adjusted
      standardized incidence ratios (SIR) were calculated as an estimate of relative
      risk for a second primary OC. Seventy-three thousand six hundred and thirteen
      women were eligible for the study, providing 486 679 person years at risk for
      analysis. One hundred and thirty-two second primary OCs were observed, compared
      with 121 expected (SIR 1.09; 95% confidence interval: 0.91-1.29). Radiotherapy
      treatment in 37 888 women did not affect the risk of a second primary OC (SIR
      1.07; 95% confidence interval: 0.79-1.41). No difference was identified when
      examined by OC morphology.There was no association between breast cancer and a
      second primary OC. Radiotherapy that avoids deep irradiation in the treatment of
      breast cancer, local nodes or recurrence was not associated with an increased
      risk of developing a second primary OC.

PMID- 20145542
TI  - Ocular surface comfort during the day assessed by instant reporting in different
      types of contact and non-contact lens wearers.
AB  - OBJECTIVE: To compare instant reporting of comfort throughout the day in
      hydrogel, silicone-hydrogel, gas-permeable, and non-contact lens wearers.
      METHODS: More than twenty subjects were recruited per group. Comfort scores were
      recorded using short message service (text message) in the morning (9:00-11:00
      am), afternoon (2:00-4:00 pm), and night (7:00-9:00 pm) using a 0 (causes pain)
      to 100 (excellent) scale. RESULTS: The pooled comfort scores across all groups
      and time periods revealed that data are skewed toward high values: 88% of the
      scores felt between >or=70 and 100, whereas the remaining 12% felt between >or=40
      and <70. Comfort changed significantly over time (P=0.003), but no significant
      differences were found between groups (P=0.66) or in the interaction between time
      and group (P=0.79). Hydrogel and silicone-hydrogel contact lens-wearing groups
      showed similar reductions in afternoon (-4.5 +/- 11.8 and -4.5 +/- 8.6,
      respectively) and night comfort scores (-8.3 +/- 14.1 and -9.1 +/- 8.7,
      respectively), and these were greater than those found in gas-permeable and non
      contact lens wearers both in the afternoon (-1.0 +/- 11.3 and -1.8 +/- 16.3,
      respectively) and night (-7.3 +/- 9.7 and -4.1 +/- 21.9, respectively).
      DISCUSSION: Hydrogel and silicone-hydrogel contact lens wearers' comfort scores
      are reduced at night compared with morning. The slight comfort reduction at night
      versus morning found in non-contact lens wearers might be related to ocular or
      general physical fatigue, which suggest the possibility that reduced end-of-day
      comfort reported by contact lens wearers might not be solely related to contact
      lens wear. The results of this study also suggest that interpretation of comfort
      scores should be carried out with caution.

PMID- 20145543
TI  - Retrospective analysis of vision correction and lens tolerance in keratoconus
      patients prescribed a contact lens with dual aspherical curves.
AB  - OBJECTIVES: To determine whether Aphex KC, a newly designed rigid gas-permeable
      (RGP) contact lens with dual aspherical base curves, improves visual acuity and
      lens wear time in patients with keratoconus. METHODS: We performed a
      retrospective analysis of a noncomparative case series of 29 eyes of 24 patients
      with keratoconus who were intolerant of spherical RGP contact lenses and were
      fitted with Aphex KC at Yamaguchi University Hospital. Visual acuity and lens
      wear time were recorded as primary outcome measures at follow-up visits. Six
      patients with a follow-up period of <1 year were excluded from data analysis. At
      the last follow-up visit, 86.2% of eyes (25 eyes of 20 patients) continued to
      wear Aphex KC. RESULTS: Mean uncorrected visual acuity was 1.4 LogMAR (20/500 in
      Snellen notation) for the 29 eyes enrolled in the study. Mean best-corrected
      visual acuity was 0.1 LogMAR (20/25) with Aphex KC and 0.7 LogMAR (20/111) with
      glasses (P < 0.001). A total of 19 eyes (65.5%) had a best-corrected visual
      acuity of 0.2 LogMAR (20/29) or better with Aphex KC. The mean +/- SD wear time
      was 12.6 +/- 3.2 hr/day with Aphex KC and 0.4 +/- 0.7 hr/day with a previously
      prescribed spherical RGP contact lens (P = 1 x 10). The numbers of eyes wearing
      Aphex KC or the previously prescribed RGP contact lens for >12 hr/day were 26 and
      0, respectively (P = 1 x 10). No serious complications of Aphex KC wear were
      observed. CONCLUSIONS: Fitting of an Aphex KC lens improved visual acuity and
      increased lens wear time in keratoconus patients who were intolerant of a
      spherical RGP contact lens. Aphex KC thus provides a viable alternative for
      management of such patients.

PMID- 20145544
TI  - Upper and lower tear menisci after laser in situ keratomileusis.
AB  - OBJECTIVES: To determine upper and lower tear menisci using optical coherence
      tomography (OCT) in volunteers after laser in situ keratomileusis (LASIK) for
      myopia. METHODS: Thirty-five eyes of 35 nonsurgical volunteers were evaluated.
      Twenty-eight eyes of 28 volunteers who underwent LASIK served as the study group.
      The height, area, and volume of the upper and lower tear menisci were obtained in
      the study group, using OCT before surgery, 1 week, 1 month, and 20 months after
      surgery. At each visit, Schirmer test (type I, without anesthesia), tear break-up
      time, and corneal fluorescein staining score were evaluated. OCT imaging was
      conducted in the nonsurgical group with the same settings. RESULTS: The lower
      tear meniscus volume at baseline were significantly smaller in the study group
      compared with the nonsurgical group (t test, P < 0.01). The upper tear meniscus
      volume decreased from 0.44 +/- 0.11 microL to 0.37 +/- 0.08 microL at 1 month
      after surgery (P < 0.05). The lower tear meniscus volume (0.54 +/- 0.15 microL)
      reduced to 0.44 +/- 0.10 microL at 1 month after surgery (posthoc, P < 0.05). For
      the subgroup analysis, tear menisci, Schirmer test, and tear break-up time after
      LASIK decreased during the first 1 month (P < 0.05) and recovered by 20 months
      after surgery (t test, P > 0.05). CONCLUSIONS: The upper and lower tear menisci
      decreased up to 1 month after LASIK and recovered by 20 months. OCT is a useful
      tool for evaluating the tear system in a noninvasive manner.

PMID- 20145545
TI  - IL-2-driven regulation of NK cell receptors with regard to the distribution of
      CD16+ and CD16- subpopulations and in vivo influence after haploidentical NK cell
      infusion.
AB  - To characterize natural killer (NK) cell subpopulations during activation, we
      analyzed the NK cell receptor repertoire and functionality of purified clinical
      scale CD56CD3 donor NK cells during stimulation with 1000 U/mL interleukin (IL)-2
      for up to 14 days. In a phase I/II trial, we investigated the efficacy and
      feasibility of nonidentical NK cell infusion in patients with neuroblastoma after
      haploidentical stem cell transplantation. After IL-2 stimulation, large
      differences in the distribution of CD16 and CD16 subpopulations were found in 12
      donors. Thereby, surface expression for all natural cytotoxicity receptors (NCRs)
      and NKG2D increased. In addition, killer cell immunoglobulin-like receptor (KIR)
      NK cells were overgrown by KIR proportion and the homing receptor CD62L was lost
      during stimulation. NK cell cytotoxicity against K562 and neuroblastoma cells
      increased and significantly higher cytokine secretion (eg, interferon-gamma,
      tumor necrosis factor-beta, macrophage inflammatory protein-1alpha, macrophage
      inflammatory protein-1beta) was observed after IL-2 stimulation compared with
      freshly isolated NK cells. However, NK cells of donors showing an initially
      enhanced cytotoxicity combined with NCR and CD69 expression, seemed to be
      exhausted and did not favor a stimulation period over 9 days. When IL-2
      stimulated NK cells were given to transplant recipients, they induced a decrease
      of peripheral blood NK, in particular of CD56-NK cells. Our data indicate that IL
      2 stimulation increases the expression of activating receptors and emphasizes
      mechanisms beside KIR/human leukocyte antigen. Furthermore, the results suggest
      that the expansion period of purified NK cells has to be individualized to
      optimize NK cell immunotherapy.

PMID- 20145546
TI  - A phase 2 trial of immunotherapy with mitumprotimut-T (Id-KLH) and GM-CSF
      following rituximab in follicular B-cell lymphoma.
AB  - We evaluated the efficacy and safety of patient-specific immunotherapy with
      mitumprotimut-T idiotype keyhole limpet hemocyanin and granulocyte-monocyte
      colony-stimulating factor (GM-CSF) following rituximab in patients with
      follicular B-cell lymphoma. Patients with previously untreated or
      relapsed/refractory CD20+ follicular lymphoma received 4 weekly infusions of
      rituximab and those with a complete response (CR), partial response (PR), or
      stable disease received mitumprotimut-T and GM-CSF injections subcutaneously.
      Courses were given monthly for 6 doses, every 2 months for 6 doses, and then
      every 3 months until disease progression. Computed tomography scans were obtained
      every 3 to 6 months and reviewed centrally. The primary endpoint was event-free
      survival (EFS). Among 103 patients treated with rituximab, 92 (54
      relapsed/refractory and 38 previously untreated) received mitumprotimut-T/GM-CSF;
      median age was 53 years, 91% had stage III to IV disease, and 59% had failed
      earlier therapy. The premitumprotimut-T objective response rate was 47% (2 CRs,
      41 PRs). During the mitumprotimut-T treatment phase, 16 patients converted to CR
      resulting in an overall objective response rate of 60% (18 CRs, 37 PRs). Median
      EFS was 15.2, 20.8, and 13.5 months for all, treatment-naive, and
      relapsed/refractory disease patients, respectively. Anti-Id cellular immune
      responses were detected in 13 of 18 (72%) patients and humoral immune responses
      in 17 of 83 (20%) patients. Adverse events were usually mild-to-moderate. The
      most common adverse event was injection site reactions. Mitumprotimut-T/GM-CSF
      induced anti-Id cellular immune responses in most patients. The occurrence of
      late CRs and favorable EFS suggested a clinical benefit of active immunotherapy
      and led to a placebo-controlled phase 3 trial.

PMID- 20145547
TI  - A myeloid cell population induced by Freund adjuvant suppresses T-cell-mediated
      antitumor immunity.
AB  - Although adjuvants are important components of vaccines, few studies have been
      conducted to establish the criteria on adjuvant selection and to investigate
      mechanisms of adjuvant actions during vaccination. Here we found that complete
      Freund adjuvant (CFA) induced a CD11b cell population in a B-cell independent
      manner. This cell population exhibited strong ability to inhibit T-cell-mediated
      rejection of tumor transplants. In vitro studies indicated that these cells
      induced T-cell apoptosis and down-regulated interferon-gamma production. Nitric
      oxide (NO) played important roles to achieve these effects. Plenty of NO was
      produced by these CFA-induced CD11b cells. The addition of N-nitro-L-arginine
      methyl ester, an inhibitor of NO synthase, rescued T cells from apoptosis and
      partially abrogated the detrimental effects of CFA in cancer vaccines. Incomplete
      Freund adjuvant, one of the adjuvants still being used in clinical trials, also
      induced a similar cell population. Our results reveal a previously unknown
      mechanism in which the myeloid cell population induced by Freund adjuvant impairs
      antitumor immunity, and highlight the importance of adjuvant selection during
      tumor vaccination.

PMID- 20145548
TI  - Generation of tumor-specific T lymphocytes using dendritic cell/tumor fusions and
      anti-CD3/CD28.
AB  - Adoptive immunotherapy with tumor-specific T cells represents a promising
      treatment strategy for patients with malignancy. However, the efficacy of T-cell
      therapy has been limited by the ability to expand tumor-reactive cells with an
      activated phenotype that effectively target malignant cells. We have developed an
      anticancer vaccine in which patient-derived tumor cells are fused with autologous
      dendritic cells (DCs), such that a wide array of tumor antigens are presented in
      the context of DC-mediated costimulation. In this study, we demonstrate that
      DC/tumor fusions induce T cells that react with tumor and are dramatically
      expanded by subsequent ligation of the CD3/CD28 costimulatory complex. These T
      cells exhibit a predominantly activated phenotype as manifested by an increase in
      the percentage of cells expressing CD69 and interferon gamma. In addition, the T
      cells upregulate granzyme B expression and are highly effective in lysing
      autologous tumor targets. Targeting of tumor-specific antigen was demonstrated by
      the expansion of T cells with specificity for the MUC1 tetramer. Stimulation with
      anti-CD3/CD28 followed by DC/tumor fusions or either agent alone failed to result
      in a similar expansion of tumor-reactive T cells. Consistent with these findings,
      spectratyping analysis demonstrates selective expansion of T-cell clones as
      manifested by considerable skewing of the Vbeta repertoire following sequential
      stimulation with DC/tumor fusions and anti-CD3/CD28. Gene expression analysis was
      notable for the upregulation of inflammatory pathways. These findings indicate
      that stimulation with DC/tumor fusions provides a unique platform for subsequent
      expansion with anti-CD3/CD28 in adoptive T-cell therapy of cancer.

PMID- 20145549
TI  - Combining T-cell vaccination and application of agonistic anti-GITR mAb (DTA-1)
      induces complete eradication of HPV oncogene expressing tumors in mice.
AB  - We generated an adenovirus-based T-cell vaccine (Ad-p14) that reliably elicits T
      cell responses to human papillomavirus (HPV) oncogenes of the 2 most common high
      risk HPV serotypes. The artificial gene used to create the vaccine comprising 415
      aa (1248 bp) was cloned by fusing 14 polymerase chain reaction fragments of HPV16
      and HPV18 E6 and E7 oncogenes devoid of sequences with transforming potential.
      Although ensuring maximal biologic safety, the construct includes approximately
      70% of the relevant T-cell epitopes. In a tumor model for cervical cancer (C3),
      therapeutic vaccination led to complete eradication in 100% of the mice. In a
      second model (TC1), it induced initial tumor mass reduction, but 90% of the
      animals showed delayed tumor progression. To further improve the therapeutic
      effect, vaccination was combined with systemic application of imiquimod, anti
      CD4, alpha-interferon, or anti-GITR. Although adding alpha-interferon improved
      the therapeutic potential of Ad-p14 by 40%, the combination with anti-GITR
      resulted in complete and permanent eradication of all TC1 tumors. Ad-p14 has
      clinical potential for treating HPV-induced lesions, and the added effect of
      immune response modifiers stresses the importance of combined protocols for
      immunotherapy of malignant tumors.

PMID- 20145551
TI  - Conditioning of the injection site with CpG enhances the migration of adoptively
      transferred dendritic cells and endogenous CD8+ T-cell responses.
AB  - The efficiency of immunotherapy using tumor-antigen-loaded dendritic cells (DCs)
      is severely limited by the impaired migration of injected cells from the
      application site to the draining lymph nodes. As described earlier, pretreatment
      of the injection site with inflammatory cytokines enhances DC migration. We
      wanted to test whether toll-like receptor (TLR) ligands can improve migration of
      murine bone marrow-derived DC (BMDC) and the subsequent T-cell responses. For
      this purpose, we established an experimental setup closely resembling human
      vaccination protocols that served to investigate DC migration from the skin to
      the draining lymph nodes. We observed that BMDC, matured with a cytokine cocktail
      (tumor necrosis factor-alpha, interleukin-beta, interleukin-6, prostaglandin E2),
      strongly expressed CCR7. The migration efficiency of adoptively transferred
      mature BMDCs was determined by the number of cells injected and the application
      site. We decided to inject DC intradermally into the ear skin and investigated
      the effects of pretreatment of the injection site with various TLR ligands.
      Conditioning of the skin site with the TLR ligands CpG and Peptidoglycan
      increased the number of DCs arriving in the lymph node. Mechanical stress applied
      to the skin, such as tape stripping of the skin was equally effective.
      Importantly, only pretreatment with CpG enhanced responses of endogenous CD8 T
      cells. Thus, conditioning of the injection site with the TLR ligand CpG could be
      a new promising way to improve the outcome of DC immunotherapy.

PMID- 20145552
TI  - Intensity and duration of intermittent exercise and recovery during a soccer
      match.
AB  - Soccer is a sport consisting of high-intensity intermittent exercise, with
      players making forays across their anaerobic threshold for tactical advantage
      followed by periods of recovery. The intensity and duration of these work and
      recovery bouts were defined during a men's soccer match using StepWatch Activity
      Monitors recording step rate for each 3-second period. The data were coded by
      custom software to separate work bouts (step rate >= 4) from recovery bouts (step
      rate < 4), and a square wave of the pattern of bouts was plotted for 5 players:
      center forward, central midfielder, wing midfielder, central defender, and wing
      defender. Four values were calculated for each work and recovery bout identified:
      duration, and mean, maximum, and minimum step rate (intensity). This novel
      technique provided detailed graphical information on the duration and exercise
      intensity of each position throughout the match. The center midfielder was able
      to sustain work and recovery bout characteristics throughout the match and
      appeared to recover at higher intensity levels than other players. The forward
      showed the consequence of accumulated fatigue late in the match and was unable to
      sustain the duration of high-intensity work bouts observed earlier in the match.
      The central defender attenuated the intensity of his work and recovery bouts late
      in the match staying closer to a more moderate work rate with fewer high- or low
      intensity bouts. Having objective data qualifying players' work and recovery bout
      characteristics might prove valuable for tactical decision making, substitution
      timing, and for planning future training sessions.

PMID- 20145550
TI  - Tumor secretion of VEGF induces endothelial cells to suppress T cell functions
      through the production of PGE2.
AB  - Endothelial cells are potent regulators of immune cell functions and have
      therefore been examined to determine their role in tumor-induced immune
      suppression. Previous studies by our laboratory showed that exposure to Lewis
      lung carcinoma (LLC)-secreted products induced endothelial cells to suppress T
      cell functions in vitro. The current studies examined in vitro and in vivo the
      mechanism by which tumors induce the formation of suppressor endothelial cells
      and the means by which suppressor endothelial cells disrupt T-cell functions. In
      vitro studies demonstrated that inhibition of tumor-derived VEGF with
      neutralizing antibodies or treatment of endothelial cells with the VEGF receptor
      tyrosine kinase inhibitor, SU5416, prevented endothelial cells from being induced
      to suppress T-cell functions. Treatment of tumor-bearing mice with SU5416 blocked
      the development of endothelial cells that are suppressive to CD4 and CD8 T-cell
      functions. We next examined the role of suppressor endothelial cell-derived PGE2
      in the inhibition of T-cell functions. Abrogation of endothelial cell PGE2
      production in vitro with indomethacin prevented tumor-conditioned media from
      stimulating endothelial cell production of immune inhibitory activity toward T
      cell functions. Similar treatment of endothelial cells from lungs of tumor
      bearing mice blocked their capacity to produce T-cell-inhibitory mediators. These
      studies demonstrate that tumor-derived VEGF induces endothelial cells to
      upregulate production of PGE2 which, in turn, leads to suppression of T-cell
      functions.

PMID- 20145553
TI  - Three types of kinematic feedback and the execution of the hang power clean.
AB  - The type and quality of feedback provided during instruction influences motor
      skill learning. The purpose of the study is to gain a better understanding of how
      altering feedback can impact discrete dynamic movements that are integral to
      strength training programs. The effects of 3 types of feedback on the execution
      hang power clean (4 sets of 4 repetitions at 75% of 1 repetition maximum) were
      evaluated over 6 training sessions. Nine different movement indices of the hang
      power clean were assessed using Dartfish video analysis software and comparisons
      among groups were made for each individually. Participants' performance was
      predicted to benefit more from a combination of visual and verbal feedback cues
      than from visual feedback alone or verbal feedback alone. Results showed that 5
      of the movement indices yielded a statistically significant interaction (p <
      0.05). Analyses of movement form indicated that with training participants in
      both the video + cues group and the verbal-only group improved, whereas
      individuals in the video-only group did not. These results have implications for
      instructors seeking efficient methods of improving the way in which to teach
      female athletes to perform complex, dynamic, and technical movements through
      altering the type of feedback given.

PMID- 20145554
TI  - Effects of vibration training on muscle power: a meta-analysis.
AB  - The purpose of this meta-analysis was to attempt to gain a clear picture of the
      magnitude of adaptations in muscular power expected after acute and chronic
      training, as well as identify specific factors that influence the treatment
      effects. Studies using a power training intervention and containing data
      necessary to calculate effect size (ES) were included in the analysis a total of
      30 studies. Effect size demonstrated that the type of vibration platform used is
      a moderator of the treatment effect of vibration on power development is the type
      of vibration platform employed. Differences were noted in both acute and chronic
      changes in power when vertical vibration platforms were compared with oscillating
      platforms. Vertical platforms elicit a significantly larger treatment effect for
      chronic adaptations (ES = 0.99) as compared with oscillating platforms (ES =
      0.36). The data also show that age is a moderator of the response to vibration
      exercise for power. On the basis of the overall analysis, it is apparent that
      vibration exercise can be effective at eliciting chronic power adaptations.
      Exercise professionals can include vibration exercise as a means of fostering
      power improvements.

PMID- 20145555
TI  - Whole-body vibration training increases vertical jump height in a dance
      population.
AB  - Whole-body vibration (WBV) training has gained popularity with the strength and
      conditioning environment. Previous research reported improvements in strength and
      power after WBV interventions in untrained individuals with little hypertrophical
      development of the muscles, suggesting that the improvements are because of
      neuromuscular adaptations. The present intervention study recruited moderately
      trained individuals that have jumping as integral to their training. Participants
      were randomly allocated to an intervention or control group. The intervention
      group was exposed to WBV at 35 Hz for 5 minutes twice a week, whereas the control
      group was exposed to a similar isometric contraction stress. Results indicated
      that after a 6-week intervention, vertical jump height increased significantly (p
      < 0.05) in the intervention group than in the control group. The study concluded
      that WBV was able to maintain vertical jump height with very little intervention
      time (10 minutes a week) and therefore should be considered as an intervention
      form for maintaining jump performance.

PMID- 20145556
TI  - Moderate static stretching and torque production of the knee flexors.
AB  - Recent studies have suggested that acute static stretching (SS) decreases
      muscular strength and performance, particularly of the knee extensors. The
      purpose of this study was to investigate the effect of SS on peak concentric and
      eccentric torque production in the knee flexors. Subjects (13 women and 16 men)
      were tested for isokinetic concentric (CON) and eccentric (ECC) peak torque at 2
      velocities (60 and 210 degrees x s(-1)) before and after a 3-minute knee flexor
      SS protocol. Subjects also underwent a control day in which the isokinetic pre-
      and posttests were separated by 10 minutes of sitting rather than stretching. A
      sit and reach test was administered on both days to assess changes in flexibility
      that occurred as a result of the stretching or control protocols. The change in
      flexibility was significantly greater after stretching than after sitting.
      Changes in peak torque were not significantly different between the stretching
      and control conditions for either velocity or contraction type. Compared with the
      control condition, SS of the knee flexors before maximal isokinetic testing does
      not lead to significantly diminished CON or ECC torque output at slow or fast
      contraction velocities. These data suggest that moderate SS does not impact the
      performance of all muscle groups.

PMID- 20145557
TI  - Effect of squatting on sprinting performance and repeated exposure to complex
      training in male rugby players.
AB  - This study was undertaken to examine the effect of a heavy weight training
      exercise on sprinting performance and on the effect of repeated exposure to a
      complex training protocol. Eleven male rugby union players (age 20.9 +/- 3.1
      years) participated in the study, which involved 5 separate testing sessions.
      Back squat 3 repetition maximum (3RM) was established in session 1. Sessions 2-5
      were identical and involved the subjects completing a 30-m sprint before and
      after a 3RM back squat protocol. Four minutes of rest was given between the back
      squatting and the posttest 30-m sprint. All sprint trials were measured with a
      laser measurement device (LAVEG, Jenoptik, Jena, Germany). Sprint time and
      instantaneous, average, and maximum velocity were the dependent variables. The
      criterion for significance was set at an alpha level of p > or = 0.05. No
      significant improvement was evident for any of the testing sessions (p > or =
      0.05). In session 1, there was a significant increase in 30-m time and a
      significant reduction in average 30-m velocity and maximum velocity (p < 0.05).
      The expected benefits in sprinting may not have been realized because of intra
      and intersubject variations in sprint technique. The session x phase interaction
      revealed a significant improvement in the pre to posttest changes in
      instantaneous velocity at 20 m (p = 0.035) and 30 m (p = 0.036) from session 1 to
      session 4. This indicates that the rugby players may be able to learn to apply
      the potentiation effects of complex training. From a practical perspective,
      players may need repeated exposure to this training modality to gain benefit from
      it, and this should be reflected in program planning.

PMID- 20145558
TI  - Salivary cortisol and immunoglobulin A responses during golf competition vs.
      practice in elite male and female junior golfers.
AB  - The purpose of this study was to investigate the stress and immune responses to a
      competition in elite male and female junior golfers. Six male (16.2 +/- 1.4
      years) and 6 female junior golfers (16.4 +/- 1.1 years) completed salivary
      collections during competition vs. practice rounds on 2 different days. Salivary
      samples were collected on 4 occasions (rest, before, during, and after rounds).
      Salivary cortisol and IgA were measured for stress and immune responses,
      respectively. Our results were as follows: (a) Salivary cortisol level was higher
      in competition than practice in male golfers (p = 0.009) but it was similar in
      female golfers. In male golfers, salivary cortisol level was higher before a
      round than at rest (p = 0.029), but it was higher after rounds than at rest (p =
      0.016) in female golfers. (b) Salivary IgA was elevated during competition than
      during practice rounds in male golfers (p = 0.019), but not in females (p =
      0.152). Salivary IgA was not significantly different among salivary collection
      times although it tended to be elevated during and after rounds for both male and
      female golfers. In conclusion, salivary cortisol and IgA were elevated during
      golf competition compared with practice in male junior golfers, but they were not
      in female golfers. Furthermore, salivary cortisol was higher before a round than
      rest in men, but it was higher after a round than rest in women. Both male and
      female junior golfers, however, showed similar salivary IgA responses during
      golf. Our results suggest that sex might play a role on stress and immune
      responses during a game of golf in elite junior golfers.

PMID- 20145559
TI  - Correlations between injury, training intensity, and physical and mental
      exhaustion among college athletes.
AB  - The primary purpose of this research was to obtain information concerning injury
      incidence and perceptions of training intensities and fatigue levels among
      college athletes via a survey study. A second purpose was to illuminate
      correlations between the collected data. This study employed an investigator
      designed survey instrument administered to 411 NCAA Division II male and female
      athletes, with 149 completed responses. The survey included 3 themes: injury
      incidence, training intensity, and physical and mental exhaustion. Men and women
      spent 4.5 days per week training using moderate- and high-intensity levels. Fifty
      percent of the total number of athletes reported chronic injury. During the
      competition season, physical exhaustion occurred "frequently" 30.86 and 23.53% of
      the time with men and women, respectively. In the noncompetition season, physical
      exhaustion was "frequently" experienced 19.75 and 17.65% of the time among men
      and women, respectively. Statistically significant correlations (p < 0.05) were
      found with acute injury for men and chronic injury for women. Also, training
      intensity levels and physical and mental exhaustion for men and women were
      statistically significant. The current investigators found the training involved
      2-3 hours of moderate to high intensity 4.5 days per week both during competition
      and noncompetition; women and men spent 2-3 hours of light intensity 1.31 and
      1.45 days per week, respectively. Women and men in addition to training, engaged
      in 3.78 and 4.43 hours of leisure physical activity per week. The investigators
      recommend tapering, periodization, and rest to help avoid overuse syndrome,
      overreaching, and overtraining that leads to excessive physical and mental
      exhaustion and injury.

PMID- 20145560
TI  - Acute effects of Flexi-bar vs. Sham-bar exercise on muscle electromyography
      activity and performance.
AB  - This study was conducted to investigate whether the low-frequency (5-Hz)
      oscillatory vibration-like stimulus, purported to be delivered by exercising with
      Flexi-bar, acutely affects muscle activation and maximal voluntary contraction
      (MVC) force. Nine healthy men participated in 2 trials, separated by at least 1
      week, during which 4 x 30-second sets of exercise were performed with either the
      Flexi bar or a Sham bar. Maximal voluntary contraction force for elbow flexion,
      elbow extension, and knee extension were measured before and after the exercise.
      Root-mean-square amplitude and median frequency of electromyography (EMG) signal
      were calculated for the first and last 10 seconds of each exercise set and during
      the MVCs from biceps brachii (BB), triceps brachii (TB), rectus femoris (RF), and
      vastus lateralis (VL) for each trial. Electromyography amplitude was
      significantly higher for all studied muscles during Flexi-bar than Sham-bar
      exercise (32-203%, p < 0.05). Median frequency of EMG power spectrum was
      significantly lower in arm (TB: -40 +/- 13%, p < 0.0001; BB: -32 +/- 25%, p =
      0.015) but not in leg (RF: -12 +/- 18%; VL: +6 +/- 32%; p > 0.05) muscles during
      Flexi-bar compared with Sham-bar exercise. Knee extension MVC force significantly
      decreased after Flexi-bar exercise (-3 +/- 7%, p = 0.048) in parallel with
      reduced RF EMG amplitude (-8 +/- 5%, p = 0.04), but there were no acute residual
      effects on elbow flexion/extension MVC or arm and VL EMG muscle activity. Using
      Flexi bar during exercise provoked acute alterations in arm- and leg-muscle EMG
      parameters and maximum force-generating capacity, indicating greater fatigue
      development than when exercising with the Sham bar. The results of this study
      indicate that Flexi bar may therefore be used to impose a stronger training
      stimulus on the muscle during submaximal exercise.

PMID- 20145561
TI  - After-school fitness performance is not altered after physical education lessons
      in adolescent athletes.
AB  - Physical education (PE) provides a unique opportunity for school-age youth to
      establish health habits, although some young athletes are exempt from PE and
      others do not participate because of a concern regarding the lingering effects of
      fatigue on after-school fitness performance. The purpose of this study was to
      examine the acute effects of different PE lessons on after-school fitness
      performance in young athletes. Twenty athletes (14-18 years) participated in 3
      different PE lessons that consisted of aerobic exercise (AE), resistance training
      (RT), or basketball skill training (BS). Fitness performance was assessed after
      school following each lesson and after a control day without PE. There were no
      significant differences in flexibility (34.1 +/- 6.5, 34.7 +/- 1.3, 33.5 +/- 7.2,
      and 33.6 +/- 7.3 cm), vertical jump (46.3 +/- 14.7, 46.2 +/- 13.6, 46.4 +/- 13.4,
      and 45.6 +/- 14.2 cm), long jump (175.0 +/- 36.4, 174.2 +/- 36.3, 172.7 +/- 35.8,
      and 171.9 +/- 34.7 cm), medicine ball toss (348.9 +/- 121.8, 342.0 +/- 120.6,
      353.9 +/- 123.6, and 348.4 +/- 129.1 cm), proagility shuttle run (5.8 +/- 0.5,
      5.7 +/-0.53, 5.8 +/- 0.52, and 5.8 +/- 0.5 seconds), 20-m sprint (3.7 +/- 0.4,
      3.7 +/- 0.4, 3.7 +/- 0.3, and 3.7 +/- 0.3 seconds), and 200-m sprint (36.3 +/-
      4.7, 35.1 +/- 4.0, 35.9 +/- 5.9, and 35.4 +/- 5.4 seconds) after AE, RT, BS, or
      the control day, respectively. These findings suggest that an exercise lesson or
      skill-based PE class will not have an adverse effect on after-school fitness
      performance in adolescent athletes.

PMID- 20145562
TI  - Cystine and theanine supplementation restores high-intensity resistance exercise
      induced attenuation of natural killer cell activity in well-trained men.
AB  - We investigated the effects of supplementation with cystine, a dipeptide of
      cysteine, and theanine (CT), a precursor of glutamate, on immune variables during
      high-intensity resistance exercise. Cysteine and glutamate are involved in the
      formation of glutathione, which modulates the activity of natural killer (NK)
      cells. In this double-blinded clinical trial, 15 well-trained men (aged 22.8 +/-
      4.0 years) were divided into 2 groups: placebo (n = 7) and CT (n = 8). The
      placebo group was administered a powder containing cellulose (950 mg) and
      glutamate (30 mg), whereas the CT group was administered a powder containing
      cystine (700 mg) and theanine (280 mg), once daily for 2 weeks. The subjects
      trained according to their normal schedule (3 times per week) in the first week
      and trained at double the frequency (6 times per week) in the second week.
      Concentrations of immunoglobulin (Ig)M, interleukin (IL)-6, IL-8, and salivary
      IgA and the leukocyte count did not change significantly in either group. There
      was a significant decrease (p < or = 0.05) in the NK cell activity (NKCA) in the
      placebo group after the second week compared with that in the CT group (placebo:
      69.2 +/- 16.1% vs. CT: 101.7 +/- 38.7%). Phytohemagglutinin-induced lymphocyte
      blastoid transformation did not change significantly in either group. These
      results suggest that NKCA is not affected in a normal training schedule with or
      without CT supplementation. However, high-intensity and high-frequency resistance
      exercises cause attenuation of NKCA, which CT supplementation appears to restore.
      Therefore, in practical application, CT supplementation would be useful for
      athletes to restore the attenuation of NKCA during high-intensity and high
      frequency training.

PMID- 20145563
TI  - Prediction of aerobic capacity in firefighters using submaximal treadmill and
      stairmill protocols.
AB  - Accurate assessments of aerobic capacity are essential to ensuring the health and
      well-being of firefighters, given their arduous and stressful working conditions.
      The use of a submaximal protocol, if proven accurate, addresses concerns such as
      administrative cost, time, and ease of test performance. The purposes of this
      study were to develop and validate graded submaximal and maximal stairmill
      protocols and to develop accurate maximal and submaximal equations to predict
      peak VO2 using both the stairmill and Gerkin treadmill protocols. Fifty-four
      subjects, men (36.3 +/- 5.6 years) and women (36.4 +/- 6.3 years), performed
      maximal graded exercise tests using both the stairmill and Gerkin treadmill
      protocols. Significant predictors of peak VO2 included body mass index, time to
      completion for maximal protocols, and time to 85% of predicted maximal heart rate
      for submaximal protocols. Maximal prediction equations were more accurate on both
      the treadmill (R = 0.654, standard error of the estimate [SEE] = 3.73 ml x kg(-1)
      x min(-1)) and stairmill (R = 0.816, SEE = 2.89 ml x kg(-1) x min(-1)) than
      developed submaximal prediction equations for both the treadmill (R = 0.325, SEE
      = 5.20 ml x kg(-1) x min(-1)) and stairmill (R = 0.480, SEE = 4.85 ml x kg(-1) x
      min(-1)). Both of the newly developed submaximal prediction equations more
      accurately predict peak VO2 than the current Gerkin equation. In summary, we
      support the use of both the stairmill and treadmill as a means for aerobic
      assessment in this population. The use of the developed submaximal prediction
      equations should lead to a reduced cost and time of assessment; however, direct
      measurement of maximal oxygen consumption remains the better alternative.

PMID- 20145564
TI  - Effects of low- and high-volume stretching on bench press performance in
      collegiate football players.
AB  - The purpose of this study was to determine the effects of acute low- and high
      volume static and proprioceptive neuromuscular facilitation (PNF) stretching on 1
      repetition maximum (1RM) bench press. Fifteen healthy male National Collegiate
      Athletic Association Division II football players (age: 19.9 +/- 1.1 years;
      weight: 98.89 +/- 13.39 kg; height: 184.2 +/- 5.7 cm; body composition: 14.6 +/-
      7.4%; and 1RM bench press: 129.7 +/- 3.3 kg) volunteered to participate in the
      study. Subjects completed 5 different stretching protocols integrated with a 1RM
      dynamic warm-up routine followed by 1RM testing in randomly assigned order. The
      protocols included (a) nonstretching (NS), (b) low-volume PNF stretching
      (LVPNFS), (c) high-volume PNF stretching (HVPNFS), (d) low-volume static
      stretching (LVSS), and (d) high-volume static stretching (HVSS). Two and 5 sets
      of stretching were completed for the low- and high-volume protocols,
      respectively. The stretching protocols targeted triceps and chest/shoulder muscle
      groups using 2 separate exercises. There were no significant differences in 1RM
      bench press performance (p > 0.05) among any of the stretching protocols NS
      (129.7 +/- 3.3 kg), LVPNFS (128.9 +/- 3.8 kg), HVPNFS (128.3 +/- 3.7 kg), LVSS
      (129.7 +/- 3.7 kg), and HVSS (128.2 +/- 3.7 kg). We conclude that low- and high
      volume PNF and static stretching have no significant acute effect on 1RM bench
      press in resistance-trained collegiate football players. This suggests that
      resistance-trained athletes can include either (a) a dynamic warm-up with no
      stretching or (b) a dynamic warm-up in concert with low- or high-volume static or
      PNF flexibility exercises before maximal upper body isotonic resistance-training
      lifts, if adequate rest is allowed before performance.

PMID- 20145565
TI  - Influence of postactivation potentiation on sprinting performance in professional
      rugby players.
AB  - After a bout of high-intensity exercise of short duration (preload stimulus), the
      muscle is in both a fatigued and potentiated (referred to as postactivation
      potentiation [PAP]) state. Consequently, subsequent muscle performance depends on
      the balance of these 2 factors. Although research has shown PAP to be an
      effective method of increasing power during both the squat jumps, little data
      exist on its effect on more functional activities such as sprinting. The present
      study aimed to determine the effect of PAP on sprint performance in professional
      rugby players. Sixteen professional male rugby players performed 5 10-m sprints
      (with a 5-m split): baseline, 4, 8, 12, and 16 minutes after the preload stimulus
      (1 set of 3 repetitions of the back squat at 91% 1 Repetition Maximum [RM]).
      There was no significant time effect over the duration of the study with regard
      to 5-m (p = 0.175) and 10-m sprint times (p = 0.401). However, when individual
      responses to PAP were taken into account, a significant improvement in sprint
      performance was observed over both 5 (Baseline: 1.09 +/- 0.06s vs. Best time:
      1.05 +/- 0.05s, p = 0.002) and 10 m (Baseline: 1.83 +/- 0.08s vs. Best time: 1.79
      +/- 0.08s, p = 0.003) compared with the baseline sprint. We conclude that
      sprinting performance is enhanced after a preload stimulus providing adequate and
      individualized recovery is given between the 2 activities, and this may have
      important implications for training speed.

PMID- 20145566
TI  - Supervised moderate intensity resistance exercise training improves strength in
      Special Olympic athletes.
AB  - The purpose of this study was to examine the effects of a moderate intensity
      resistance training program on Special Olympic athletes (SOAs) and similarly aged
      typically developed volunteers (TDs) who also served as coaches. Fifteen SOAs and
      17 TDs participated (age range 19-24 years). The intervention consisted of
      resistance training: 1 set, 8-12 reps, over 10-12 sessions, on Med-X weight
      equipment. Exercises tested were seated row (SR), leg curl (LC), leg extension
      (LE), chest press (CP), and the abdominal crunch (AC). The weight lifted, and the
      amount of repetitions performed at the beginning and end of training, were used
      to determine the predicted 1 repetition max (1RM). A 2-way (2:group x 2:time)
      analysis of variance was computed for each exercise. Time main effects were
      detected, which indicated that predicted 1RM increased significantly for all
      participants. Specifically, these were the SR (F(1,30) = 99.238, p < 0.001); the
      LC (F(1,30) = 91.578, p < 0.001); the LE (F(1,30) = 83.253, p < 0.001); the CP
      (F(1,30) = 53.675, p < 0.001); and the AC (F(1,30) = 57.759, p < 0.001). The
      predicted 1RM values increased between 25 and 50% across the exercises tested.
      There were no group main effects or interactions. Thus, with minimal training
      time, both similar and significant strength gains can be accomplished by both
      SOAs and TDs, respectively. Supervised moderate intensity resistance training is
      recommended for the populations tested and may result in vocational and athletic
      performance gains.

PMID- 20145567
TI  - Acute effects of static stretching on squat jump performance at different knee
      starting angles.
AB  - The purpose of this study was to examine the effects of static stretching on leg
      extensor muscles during squat jump (SJ) at different knee starting angles.
      Seventeen male subjects (23 +/- 3 years, 179 +/- 5 cm, and 74 +/- 6 kg) performed
      on a force platform 2 series (preceded or not [control condition] by 10-minute
      static stretching of quadriceps and triceps surae muscles) of SJs at different
      knee starting angles: 50 degrees, 70 degrees, 90 degrees, and 110 degrees. Squat
      jump height, peak force, maximal acceleration, velocity, and power were
      calculated for each jump. The angle that maximized power development was obtained
      from the power-angle relationship. The SJ height, peak force, and maximal
      velocity increased according to angle amplitude in both control and stretching
      conditions (p < 0.01), performance being significantly lower in the stretching
      condition (p < 0.01). Peak power was obtained at 90 degrees in both control and
      stretching conditions, but was significantly lower (p < 0.01) after stretching.
      These results suggest that an acute bout of static stretching reduces power and
      force development during SJ, decrements being significantly higher at lower knee
      starting angles. Therefore, the use of static stretching may be questionable in
      those power activities requiring maximal power output at knee angles near full
      extension.

PMID- 20145568
TI  - Training volume and personal best time in marathon, not anthropometric
      parameters, are associated with performance in male 100-km ultrarunners.
AB  - We investigated the relation between selected anthropometric and training
      variables and the personal best time in a marathon with total race time in 66
      Caucasian male nonprofessional ultrarunners in a 100-km run. In the multiple
      linear regression analysis, the average weekly training volume in kilometers (r2
      = 0.224, p < 0.01) and the personal best time in a marathon (r2 = 0.334, p <
      0.01) were significantly associated with total race time, whereas no
      anthropometric variable was related to race performance (p > 0.05). We conclude
      that high training volume and a fast time in a marathon were more important for a
      fast race time in male 100-km runners than any of the determined anthropometric
      variables.

PMID- 20145569
TI  - Blood lactate and hormonal responses to prototype flywheel ergometer workouts.
AB  - The purpose of the study was to compare blood lactate and hormonal responses with
      flywheel ergometer (FERG) leg presses for preliminary assessment of workouts best
      suited for future in-flight resistance exercise. Comprised of 10 repetition sets,
      the workouts entailed 3 sets of concentric and eccentric (CE3) actions, or
      concentric-only actions done for 3 (CO3) or 6 (CO6) sets. Methods employed
      included assessment of blood lactate concentrations ([BLa-]) before and 5 minutes
      postexercise. Venous blood was also collected before and at 1 and 30 minutes
      postexercise to assess growth hormone, testosterone, cortisol concentrations
      ([GH], [T], [C]) and [T/C] ratios. [BLa-] were compared with 2 (time) x 3
      (workout) analysis of variance. Hormones were assessed with 2 (gender) x 3 (time)
      x 3 (workout) analysis of covariances. Results showed [BLa-] had a time effect.
      Growth hormone concentration showed gender x workout, gender x time, and workout
      x time interactions, whereas [T] had a 3-way interaction. [C] had gender, time,
      and workout effects. [T/C] yielded a gender x time interaction. It was concluded
      that, because CO6 and CE3 yielded similar anabolic hormonal data but the latter
      had a lower [C] 30 minutes postexercise, CE3 served as the best workout. Although
      the FERG was originally designed for microgravity, the effort put forth by
      current subjects was like that for workouts aimed at greater athletic performance
      and conditioning. Practical applications suggest that eccentric actions should be
      used for FERG workouts geared toward muscle mass and strength improvement.

PMID- 20145570
TI  - Monitoring load, recovery, and performance in young elite soccer players.
AB  - The purpose of this study was to investigate the relation between training load,
      recovery, and monthly field test performance in young elite soccer players to
      develop training guidelines to enhance performance. In a prospective,
      nonexperimental cohort design, 18 young elite soccer players registered training
      and match duration for a full competitive season by means of daily training logs.
      Furthermore, session rating of perceived exertion (RPE) and total quality of
      recovery (TQR) scores were recorded. Weekly duration (TL(d)), load (duration x
      session RPE = TL(rpe)), and TQR scores were calculated for 1 and 2 weeks before a
      monthly submaximal interval shuttle run tests to determine interval endurance
      capacity. Participants spent on average 394.4 +/- 134.9 minutes per week on
      training and game play with an average session RPE of 14.4 +/- 1.2 (somewhat
      hard) and TQR of 14.7 +/- 1.3 (good recovery). Random intercept models showed
      that every extra hour training or game play resulted in enhanced field test
      performance (p < 0.05). Session RPE and TQR scores did not contribute to the
      prediction of performance. The duration of training and game play in the week
      before field test performance is most strongly related to interval endurance
      capacity. Therefore, coaches should focus on training duration to improve
      interval endurance capacity in elite soccer players. To evaluate the group and
      individual training response, field tests should be frequently executed and be
      incorporated in the training program.

PMID- 20145571
TI  - Reliability and factorial validity of agility tests for soccer players.
AB  - The purpose of this study was to evaluate the reliability and factorial validity
      of agility tests used in soccer. One hundred fifty (n = 150), elite, male, junior
      soccer players, members of the First Junior League Team, volunteered to
      participate in the study. The slalom test (ST) sprint 4 x 5 m (S4 x 5) and sprint
      9-3-6-3-6-9 m with 180 degree turns (S180 degrees) tests had a greater
      reliability coefficient (alpha = 0.992, 0.979, and 0.976), whereas the within
      subject variation ranged between 2.9 and 5.6%. The mentioned 6 agility tests
      resulted in the extraction of 2 significant components. The S4 x 5 test had the
      lowest correlation coefficient with the first component (r = 0.38), whereas the
      correlation coefficients of the other 5 agility tests were higher than 0.63. The
      T-test (TT) showed statistically significant differences between the defenders
      and midfielders (p < 0.05) and between the defenders and attackers (p < 0.05).
      Statistical significant differences were determined between the attackers and
      defenders in the sprint 9-3-6-3-9 m with backward and forward running (SBF) and p
      < 0.05. It can be concluded that of the 6 agility tests used in this study, the
      SBF, TT, and S180 degrees are the most reliable and valid tests for estimating
      the agility of soccer players. According to the results of the study, the TT
      proved to be the most appropriate for estimating the agility of defenders, the
      SBF, and S180 degrees for estimating the agility of midfielders, whereas the S4 x
      5 test can be used for estimating the agility of attackers.

PMID- 20145572
TI  - Pilates for improvement of muscle endurance, flexibility, balance, and posture.
AB  - Many claims have been made about the effectiveness of Pilates exercise on the
      basic parameters of fitness. The purpose of this study was to determine the
      effects of Pilates exercise on abdominal endurance, hamstring flexibility, upper
      body muscular endurance, posture, and balance. Fifty subjects were recruited to
      participate in a 12-week Pilates class, which met for 1 hour 2 times per week.
      Subjects were randomly assigned to either the experimental (n = 25) or control
      group (n = 25). Subjects performed the essential (basic) mat routine consisting
      of approximately 25 separate exercises focusing on muscular endurance and
      flexibility of the abdomen, low back, and hips each class session. At the end of
      the 12-week period, a 1-way analysis of covariance showed a significant level of
      improvement (p < or = 0.05) in all variables except posture and balance. This
      study demonstrated that in active middle-aged men and women, exposure to Pilates
      exercise for 12 weeks, for two 60-minute sessions per week, was enough to promote
      statistically significant increases in abdominal endurance, hamstring
      flexibility, and upper-body muscular endurance. Participants did not demonstrate
      improvements in either posture or balance when compared with the control group.
      Exercise-training programs that address physical inactivity concerns and that are
      accessible and enjoyable to the general public are a desirable commodity for
      exercise and fitness trainers. This study suggests that individuals can improve
      their muscular endurance and flexibility using relatively low-intensity Pilates
      exercises that do not require equipment or a high degree of skill and are easy to
      master and use within a personal fitness routine.

PMID- 20145573
TI  - Influence of length-restricted strength training on athlete's power-load curves
      of knee extensors and flexors.
AB  - This study investigated whether different length-restricted strength training
      regimens affect voluntary explosive concentric power-load curves of the
      quadriceps femoris (QF) and hamstring (HAM) muscles. Thirty-two athletes were
      divided into 3 different training groups (G1-G3): G1 performed isometric training
      at knee joint angles corresponding to long muscle-tendon unit (MTU) length for QF
      and HAM; G2 conducted concentric-eccentric contraction cycles that were
      restricted to a knee joint range of motion corresponding to predominantly long
      MTU length for QF and HAM; and G3 combined the protocols of G1 and G2. Knee joint
      angle-dependent power-load curves during maximal voluntary explosive concentric
      knee extensions and flexions were measured for loads corresponding to 40, 60, and
      80% of individual 1 repetition maximum at 5 different occasions: 2 times before,
      after 5 and 8 weeks of training, and 4 weeks post training. Power values of each
      subject were normalized to the largest value produced at any knee joint position
      (percent maximum). Obtained by curve fitting, the optimal knee joint angle for
      power production of QF and HAM remained unaltered throughout the course of the
      study for all testing loads and training groups. Therefore, different strength
      training regimens with a common restriction to long MTU lengths failed to induce
      length-dependent alterations in athlete's voluntary concentric power-load curves
      of knee extensors and flexors. The approach to develop strength training programs
      that induce systematic shifts in length-dependent power production of QF and HAM
      is of direct practical relevance for athletic activities such as cycling, ice
      skating, and skiing. However, restricting the muscle excursion range during
      loading seems to be an inappropriate trigger to cause length-dependent
      alterations in athlete's voluntary concentric power-load curves.

PMID- 20145574
TI  - Reliability of alternative trunk endurance testing procedures using clinician
      stabilization vs. traditional methods.
AB  - The purpose of this study was to determine if a modified (MOD) testing method for
      previously established trunk endurance testing for flexion and extension is a
      reliable alternative. Fifty subjects were tested with the standard (ST) testing
      procedure and an MOD testing procedure on separate testing occasions 1 week
      apart. The testing procedure order and method of assessments were randomly
      selected and implemented. The MOD testing procedure used a clinician to provide
      stabilization as opposed to the ST method of belt stabilization. Interrater
      reliability for MOD procedures was 0.97 for extension and 0.93 for flexion.
      Correlation of the MOD procedure to the ST procedure was found to be 0.90 and
      0.84 for extension and flexion, respectively. From this testing, it can be
      concluded in a sample of normal college-aged subjects that an MOD testing method
      for trunk flexion and extension endurance can reliably be used as compared with
      the previously accepted ST testing methods. From a practical application
      standpoint, this allows the use of an MOD testing procedure to be implemented in
      athletic training rooms and weight rooms that may not have appropriate tables for
      the ST testing and the fact that the MOD testing procedure will most likely
      require less time commitment and greater efficiency with testing of large groups
      of subjects.

PMID- 20145576
TI  - The time course of lexical access in morphologically complex words.
AB  - Compounding, the concatenation of words (e.g. dishwasher), is an important
      mechanism across many languages. This study investigated whether access of
      initial compound constituents occurs immediately or, alternatively, whether it is
      delayed until the last constituent (i.e. the head). Electroencephalogram was
      measured as participants listened to German two-constituent compounds. Both the
      initial as well as the following head constituent could consist of either a word
      or nonword, resulting in four experimental conditions. Results showed a larger
      N400 for initial nonword constituents, suggesting that lexical access was
      attempted before the head. Thus, this study provides direct evidence that lexical
      access of transparent compound constituents in German occurs immediately, and is
      not delayed until the compound head is encountered.

PMID- 20145577
TI  - Gene expression and 18FDG uptake in atherosclerotic carotid plaques.
AB  - PURPOSE: Metabolic assessment of vascular inflammation by 2-[F]fluoro-2-deoxy-D
      glucose positron emission tomography (FDG)-PET is a promising new approach for
      the evaluation of the vulnerability of atherosclerotic plaques. Quantitative real
      time PCR allows measurement of gene expression of markers of atherosclerotic
      plaque vulnerability. These techniques were applied in advanced atherosclerotic
      disease to relate metabolism and inflammatory activity to the gene expression
      profile of the vulnerable atherosclerotic plaque. METHODS: Seventeen patients
      with clinical symptoms of cerebral vascular events (<3 months) and an additional
      ipsilateral internal carotid artery stenosis of greater than 60% were recruited.
      FDG uptake in the carotids was determined by PET/computed tomography and
      expressed as mean and maximal standardized uptake values (SUVmean and SUVmax).
      The atherosclerotic plaques were subsequently recovered by carotid
      endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18,
      matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) -
      were measured in plaques by quantitative PCR. RESULTS: In a multivariate linear
      regression model, GLUT-1, CD68, cathepsin K, and HK2 gene expression remained in
      the final model as predictive variables of FDG accumulation calculated as SUVmean
      (R=0.26, P<0.0001). In addition, a multivariate linear regression model found
      GLUT-1, CD68, cathepsin K, and HK2 gene expression as independent predictive
      variables of FDG accumulation calculated as SUVmax (R=0.30, P<0.0001).
      CONCLUSION: GLUT-1, HK2, CD68, and cathepsin K remained in both multivariate
      models and thus provided independent information regarding FDG uptake. We suggest
      that FDG uptake is a composite indicator of macrophage load, overall inflammatory
      activity and collagenolytic plaque destabilization. Accordingly, FDG-PET could
      prove to be an important predictor of cerebrovascular events in patients with
      carotid plaques.

PMID- 20145578
TI  - Electrocardiographic changes after dipyridamole infusion in patients undergoing
      myocardial perfusion imaging.
AB  - OBJECTIVES: Although the diagnostic and prognostic importance of perfusion
      defects has been clearly established, the meaning of the development and
      characteristics of electrocardiographic (ECG) changes during dipyridamole
      infusion is less well defined. This study tries to evaluate the prevalence and
      significance of ECG changes after dipyridamole infusion and their relation to
      ischemia in myocardial perfusion single-photon emission computed tomography
      (SPECT). METHODS: Two hundred patients underwent 2-day dipyridamole stress/rest
      Tc-99m-sestamibi myocardial perfusion SPECT. Basal and post dipyridamole ECGs
      were analyzed. Myocardial perfusion images were interpreted visually and
      semiquantitatively. RESULTS: New ECG changes were noted in 20.2% of cases and
      consisted of 1.1% T-wave flattening, 1.1% T-wave inversion and 14.8% ST
      depression and 4.2% psuedonormalization. Abnormal ECG changes were noted after
      dipyridamole infusion in approximately 27.7% of patients with and 14.3% of
      patients without reversible defect in myocardial perfusion SPECT. A new ST
      depression was noted in lateral leads in 72.2% of new ST changes. The mean post
      dipyridamole heart rate increment in patients with reversible or partially
      reversible defects was significantly lesser than in patients with normal
      myocardial perfusion SPECT. In addition, the corrected QT interval (QTc)
      increment in patients with reversible defects was significantly more than in
      patients with fixed defects; however, there was no difference when compared with
      patients with no defects. Using linear regression model, the severity of ST
      depression and QTc increment were significant predictors of summed difference
      score. Sensitivity, specificity, and negative and positive predictive values of
      ST-segment depression for the diagnosis of ischemia were 20.2, 89.5, 60.7, and
      58.4%, respectively. CONCLUSION: The most common ECG change seen after
      dipyridamole infusion is ST-segment depression. The new ST-segment depression
      after dipyridamole infusion is highly specific for ischemia. Reversible defects
      are associated with a lesser increment in heart rate, whereas QTc increment and
      severity of ST segment depression were significant predictors of summed
      difference score.

PMID- 20145575
TI  - Diaspirin cross-linked hemoglobin infusion did not influence base deficit and
      lactic acid levels in two clinical trials of traumatic hemorrhagic shock patient
      resuscitation.
AB  - BACKGROUND: Diaspirin cross-linked hemoglobin (DCLHb) has demonstrated a pressor
      effect that could adversely affect traumatic hemorrhagic shock patients through
      diminished perfusion to vital organs, causing base deficit (BD) and lactate
      abnormalities. METHODS: Data from two parallel, multicenter traumatic hemorrhagic
      shock clinical trials from 17 US Emergency Departments and 27 European Union
      prehospital services using DCLHb, a hemoglobin-based resuscitation fluid.
      RESULTS: In the 219 patients, the mean age was 37.3 years, 64% of the patients
      sustained a blunt injury, 48% received DCLHb resuscitation, and the overall 28
      day mortality rate was 36.5%. BD data did not differ by treatment group (DCLHb
      vs. normal saline [NS]) at any time point. Study entry BD was higher in patients
      who died when compared with survivors in both studies (US: -14.7 vs. -9.3 and
      European Union: -11.1 vs. -4.1 mEq/L, p < 0.003) and at the first three time
      points after resuscitation. No differences in BD based on treatment group were
      observed in either those who survived or those who died from the hemorrhagic
      shock. US lactate data did not differ by treatment group (DCLHb vs. NS) at any
      time point. Study entry lactates were higher in US patients who ultimately died
      when compared with survivors (82.4 vs. 56.1 mmol/L, p < 0.003) and at all five
      postresuscitation time points. No lactate differences were observed between DCLHb
      and NS survivors or in those who died based on treatment group. CONCLUSIONS:
      Although patients who died had more greatly altered perfusion than those who
      survived, DCLHb treatment of traumatic hemorrhagic shock patients was not
      associated with BD or lactate abnormalities that would indicate poor perfusion.

PMID- 20145579
TI  - Detection of bronchioloalveolar cancer by means of PET/CT and 18F-fluorocholine,
      and comparison with 18F-fluorodeoxyglucose.
AB  - AIM: Bronchioloalveolar (BAC) cancer is a source of false-negative F
      fluorodeoxyglucose (FDG) PET/computed tomography (CT) results. A few studies
      reported better diagnostic performances with PET tracers of lipid metabolism, C
      choline, or C-acetate, for the detection of well-differentiated adenocarcinoma or
      BAC. F-fluorocholine (FCH) is a lipid analogue for PET imaging, with advantages
      in terms of logistics and image resolution. We carried out this prospective pilot
      study to evaluate whether FCH PET/CT could detect lung cancer with a BAC
      component and could be more sensitive than FDG in this aim. METHODS: Fifteen
      patients with a lung nodule or lesion suspected for BAC on CT and/or with a
      history of BAC had PET/CT 60-90 min after 5 MBq FDG/kg body mass and, on a
      separate day, 10-20 min after 4 MBq FCH/kg body mass. The standard of truth was
      histology and a 6-month follow-up. RESULTS: Nine patients (12 lesions) presented
      BAC or adenocarcinoma with BAC features, two patients presented adenocarcinoma
      without BAC features (five lesions) and four patients presented benign lesions
      (15 non-malignant sites). For both FCH and FDG, patient-based sensitivity was 78%
      for detecting cancer with a BAC component and 82% for detecting malignancy. Site
      based sensitivity for detecting malignancy was 76 and 75% for detecting cancer
      with BAC features, for both radiopharmaceuticals. Specificity was similar for FCH
      and FDG (site-based 93 vs. 81%, NS). In these early-stage cancers, only one
      adrenal metastasis was observed that took up FCH and FDG. CONCLUSION: In this
      population of patients with ground-glass opacities selected on CT suggestive of
      BAC or with a history of BAC and a recent lung anomaly on CT, FCH detected all
      malignant lesions with at least a 2.0 cm short axis. However, FDG had similar
      performance.

PMID- 20145580
TI  - Totally automatic definition of renal regions of interest from 99mTc-MAG3
      renograms: validation in patients with normal kidneys and in patients with
      suspected renal obstruction.
AB  - INTRODUCTION: An image-processing algorithm (AUTOROI) has been developed to
      totally automatically (or with manual assistance) detect whole-kidney contours
      and generate renal regions of interest (ROI) for the extraction of the
      quantitative measurements used in the interpretation of Tc
      mercaptoacetyltriglycine (Tc-MAG3) renograms. METHODS: The 18-20th min dynamic
      frames post-MAG3 injection were used to automatically define boxes surrounding
      each kidney, which were then transposed to an early composite image for
      interpolative and directional background subtraction. Sobel operator and unsharp
      masking were applied for edge enhancement, and the resulting image histograms
      were equalized to better define poorly functioning kidneys. AUTOROI searched
      radially from the center of mass to define each kidney's ROI coordinates. AUTOROI
      was validated using MAG3 studies from 79 patients referred for suspected
      obstruction (79 left, 77 right kidneys) and 19 kidney donors with normal kidney
      function and no obstruction. Renal ROIs were manually defined by a nuclear
      medicine technologist with 20+ years of experience (reference standard) and an
      American Board of Nuclear Medicine certified physician. AUTOROI and physician
      ROIs were automatically compared with the reference standard to determine the
      border definition error. RESULTS: AUTOROI totally automatically detected the
      renal borders in 89% (172 of 194) of the kidneys from the entire group of 98
      patients. The 22 kidneys missed automatically were subsequently detected with the
      assistance of a single manually placed fiducial point demarcating the
      liver/kidney boundary. These 22 kidneys were shown to be associated with markedly
      reduced MAG3 clearance. The mean error of AUTOROI for all 194 kidneys was 6.66+/
      3.77 and 7.31+/-4.52 mm for the left and right kidney, respectively. The
      physician's error was 6.78+/-2.42 and 6.65+/-2.05 mm for the left and right
      kidney, respectively. This error difference between AUTOROI and the physician was
      not statistically significant. CONCLUSION: AUTOROI provides an objective and
      promising approach to automated renal ROI detection.

PMID- 20145582
TI  - Cheese is a reliable alternative meal for solid-phase gastric emptying study.
AB  - We evaluated the labeling stability of several alternative meals that could be
      used to perform solid-phase gastric emptying study. Cooked egg whites labeled
      with technetium-99m sulfur colloid served as a control. Packaged instant oatmeal
      and instant mashed potatoes were prepared by adding hot water. Cheddar cheese was
      melted. Peanut butter was added to bread. The different meals were mixed with
      technetium-99m sulfur colloid (2.2-3.7 MBq), chopped into small pieces and placed
      in a glass tube containing gastric juice. Four samples of each meal were analyzed
      after 1 and 4 h of agitation with a 3-D rotator (two samples per time point). The
      meal samples were washed with 2 ml of saline and filtered using a blood
      transfusion filter. The activity in each sample before and after filtering was
      assayed in a dose calibrator. The percentage of initial radioactivity remaining
      with the meal of admixture with gastric juice was measured and the average of the
      two samples was taken. The percentage of activity bound to the solid phase was
      98.2+/-1.9, 95.6+/-1.1, 62.1+/-1.7, 41.8+/-0.6, and 74.5+/-3.8% at 1 h and 98.5+/
      1.0, 95.8+/-2.6, 77.2+/-6.8, 55.5+/-3.4 and 40.2+/-22.1 at 4 h for egg whites,
      cheese, oatmeal, mashed potatoes and peanut butter respectively. For egg whites
      and cheese, there was no significant difference between the values at 1 and 4 h
      (P>0.8). Cheddar cheese provides an alternative meal for assessing solid gastric
      emptying in children comparable to egg whites. Oatmeal and mashed potatoes had
      low and variable labeling stability and are not recommended. In view of the
      significant proportion of pediatric patients who refuse to eat scrambled eggs or
      have allergy to eggs, the availability of other meal choices is essential. The
      versatility of cheddar cheese, which can be added to macaroni or as a topping on
      pizza, makes it a useful alternative to labeled eggs.

PMID- 20145581
TI  - Evaluation of glucose uptake by skeletal muscle tissue and subcutaneous fat in
      HIV-infected patients with and without lipodystrophy using FDG-PET.
AB  - OBJECTIVE: To evaluate differences in glucose uptake by skeletal muscle tissue
      and subcutaneous fat in HIV patients on highly active antiretroviral therapy
      (HAART) presenting with and without lipodystrophy as well as in drug-naive HIV
      patients using F-fluorodeoxyglucose (FDG) positron emission tomography. PATIENTS
      AND METHODS: Thirty-nine consecutive patients suffering from HIV: seven drug
      naive patients, 21 nonlipodystrophic patients on HAART and 11 patients on HAART,
      respectively, suffering from lipodystrophy were prospectively included. All
      patients underwent a whole-body FDG positron emission tomography examination.
      Standardized uptake values (SUV values) of muscle and subcutaneous fat were
      compared and related to demographic and biochemical variables. RESULTS: SUV mean
      values of subcutaneous fat were significantly higher in patients under HAART
      presenting with lipodystrophy when compared with untreated and treated,
      nonlipodystrophic patients (P=0.000). SUV mean values of subcutaneous fat
      significantly correlated with treatment duration (r=0.56, P=0.000) and CD4 count
      (r=0.51, P=0.001) and inversely correlated with viral load (r=-0.61, P=0.000).
      Finally, SUV mean values of thigh muscles were not significantly different
      between the three different patient groups under study. CONCLUSION: Quantitative
      FDG uptake by subcutaneous fat proved significantly higher in HIV patients under
      HAART presenting with lipodystrophy. HAART did not influence FDG uptake by human
      skeletal muscle tissue under basal conditions.

PMID- 20145583
TI  - Interaction between the UCP2 -866 G>A polymorphism, diabetes, and beta-blocker
      use among patients with acute coronary syndromes.
AB  - OBJECTIVE: UCP2 -866G>A (rs659366) has been implicated in cardiometabolic disease
      and represents a novel candidate gene for beta-blocker response, particularly
      among patients with diabetes. We assessed the function of -866G>A and its role as
      a modifier of beta-blocker treatment outcomes by diabetes status in an acute
      coronary syndrome (ACS) cohort. METHODS: ACS patients with genetic samples and 12
      months of follow-up for cardiac rehospitalizations or death (n=468) were
      assessed. The influence of -866G>A on beta-blocker treatment outcomes was
      evaluated in those with diabetes and without. To assess functional correlates of 
      866G>A, we compared uncoupling protein 2 (UCP2) expression in the skeletal muscle
      of obese participants by genotype and compared the activity of UCP2 luciferase
      promoters with -866G and -866A alleles. RESULTS: An interaction between -866G>A
      and beta-blocker treatment was found in individuals with diabetes (P=0.002) but
      not those without (P=0.79). Among G/G individuals with diabetes, discharge beta
      blocker use was associated with an 80% reduction in cardiac rehospitalization
      (adjusted hazard ratio: 0.20; 95% confidence interval: 0.04-1.02). In contrast,
      among A-carrier patients with diabetes, there was an 11-fold increase in cardiac
      rehospitalizations with discharge beta-blocker therapy (adjusted hazard ratio:
      11.75; 95% confidence interval: 1.28-108.2). Promoter activity assays showed that
      -866G had greater cyclic AMP response element binding protein-responsiveness
      compared with -866A, and compared with -866A carriers G/G individuals exhibited
      increased UCP2 expression in the skeletal muscle. CONCLUSION: We identified a
      significant interaction between -866G>A and beta-blocker response among ACS
      patients with diabetes. Furthermore, -866G conferred greater gene transcriptional
      activity than -866A in cell lines and in obese patients. These findings may help
      us gain insight into the mechanisms underlying the beneficial and detrimental
      effects of beta-blockers in those with diabetes.

PMID- 20145584
TI  - Fleur-de-Lis abdominoplasty: a safe alternative to traditional abdominoplasty for
      the massive weight loss patient.
AB  - BACKGROUND: Traditional abdominoplasty techniques often fail to adequately
      correct the complex contour deformities in the massive weight loss patient. To
      address these deformities, addition of a vertical skin resection to the
      traditional horizontal excision has become a popular procedure. The authors
      analyzed the impact of vertical (fleur-de-lis) excision on complications when
      compared with traditional transverse excision. METHODS: A review of massive
      weight loss patients enrolled in an institutional review board-approved
      prospective registry was performed on consecutive patients undergoing
      abdominoplasty by a single surgeon. Patients were included if they underwent at
      least 50 pounds of weight loss. Demographic information, procedural data, and
      outcome measures were studied. Logistic regression and t tests were performed to
      analyze differences in complication rates for both procedures and identify risk
      factors for complications. RESULTS: Four hundred ninety-nine patients met
      inclusion criteria, of whom 154 (31 percent) had a fleur-de-lis vertical
      component. The overall abdominal complication rate for all patients was 26.3
      percent, with a 5.0 percent rate of major complications. Transverse-only and
      fleur-de-lis abdominoplasty had similar rates of complications with the exception
      of a higher rate of wound infection in the fleur-de-lis group on multivariate
      analysis. Risk factors for abdominal wound complications with either procedure
      included male sex, high body mass index, concurrent component separation, and
      previous subcostal scars. CONCLUSIONS: Fleur-de-lis abdominoplasty can be safely
      performed with complication rates comparable to those of traditional
      abdominoplasty techniques. Ideal candidates are patients with upper abdominal
      skin laxity who may not achieve an adequate aesthetic result with transverse-only
      excision.

PMID- 20145585
TI  - An algorithmic approach to breast reconstruction using latissimus dorsi
      myocutaneous flaps.
AB  - BACKGROUND: Innovative surgical techniques developed by surgical oncologists have
      changed the landscape of mastectomy defects. Latissimus dorsi myocutaneous flap
      based breast reconstruction provides a reliable foundation for breast
      reconstruction. The purpose of this study was to evaluate differential skin
      island designs with latissimus dorsi myocutaneous flap breast reconstruction, and
      to develop an algorithmic approach to breast reconstruction that is applicable to
      a broad spectrum of mastectomy defects. METHODS: In this study, the authors
      retrospectively reviewed data of patients who underwent latissimus dorsi
      myocutaneous flap reconstruction following unilateral or bilateral mastectomies
      between February of 2001 and April of 2005. Patients were selected to undergo
      reconstruction under the following circumstances: (1) previously irradiated
      tissue, (2) body mass index greater than 30, (3) current tobacco use, (4)
      previous abdominopelvic surgery, and (5) patient preference. Patients were
      divided into three groups based on defect present: intact inframammary fold with
      skin deficit, intact inframammary fold without skin deficit, and absent
      inframammary fold with or without skin deficit. Differential skin island design
      was customized to the presenting mastectomy defect to optimize results and
      minimize donor-site scaring. RESULTS: Fifty-four patients underwent 64 latissimus
      dorsi myocutaneous flap reconstructions. Aesthetic outcomes and donor-site scar
      placement differed between groups. CONCLUSIONS: The authors have developed an
      algorithmic approach to latissimus dorsi myocutaneous flap breast reconstruction.
      Through critical evaluation of mastectomy defects, reconstructive breast surgeons
      can tailor skin island orientation, minimize donor-site scarring, enhance
      cosmetic outcomes, and provide a durable and natural aesthetic outcome in breast
      reconstruction with the latissimus dorsi myocutaneous flap.

PMID- 20145586
TI  - Association study of 20 genetic variants at the (D)-amino acid oxidase gene in
      schizophrenia.

PMID- 20145587
TI  - Out of the closet and into public health focus: HIV and STDs in men who have sex
      with men in middle income and resource-limited countries.

PMID- 20145588
TI  - Acceptability of male circumcision for the prevention of HIV among high-risk
      heterosexual men in Thailand.
AB  - Limited data are available on circumcision prevalence and acceptability among
      Thai men to prevent human immunodeficiency virus. Of 408 high-risk heterosexual
      men, 12.3% were circumcised. 14.2% and 24.9% expressed willingness to be
      circumcised before and after circumcision education, respectively. Neonatal
      circumcision acceptability was relatively high. One participant underwent
      circumcision at 3-month follow-up.

PMID- 20145589
TI  - Just a penile nodule...
AB  - In this paper we present a case history of a homosexual HIV-positive male with a
      painless nodule on the penis. Screening for sexually transmitted diseases did not
      detect any infection until the node perforated spontaneously. A diagnosis of
      lymphogranuloma venereum was made when chlamydia trachomatis type L2 DNA was
      extracted from the lesion. This case illustrates that standard screening may not
      be sufficient for making the diagnosis of lymphogranuloma venereum.

PMID- 20145590
TI  - Iron deficiency anemia and cardiac mortality in patients with left ventricular
      systolic dysfunction undergoing coronary stenting.
AB  - AIM: The aim of this study was to assess cardiac mortality in patients with
      reduced ejection fraction (EF< or =45%) and anemia (Hb< or =12 g/dL) undergoing
      coronary stenting and to investigate whether iron-deficiency anemia influenced
      outcome when compared to non-anemic patients or patients with other types of
      anemia. METHODS: One hundred twenty consecutive patients undergoing percutaneous
      coronary intervention (PCI) between April 2003 and December 2005 were identified
      and followed for a median of 30 months. Patients were divided into 2 groups,
      anemic (Hb< or =12 g/dL) and non-anemic. Anemic patients were then divided into 3
      sub-groups based on laboratory analysis and anemia work-up: iron-deficiency,
      malignancy-associated, and anemia of chronic disease (including chronic kidney
      disease). Mortality rates and cause of death were retrieved using both the Social
      Security database and the hospital records. RESULTS: Thirty-one percent of
      patients had iron deficiency, 24% had a malignancy-associated anemia and 45% had
      anemia of chronic disease. Overall mortality was 12% of which 29% was cardiac
      death. All-cause and cardiac mortality were significantly higher in anemic vs.
      non-anemic patients, (31% vs. 6%, P<0.001, and 10% vs. 1%, P=0.016,
      respectively). Iron-deficiency anemia strongly predicted cardiac mortality (33%
      vs. 1% in non-anemic patients, P<0.001), while malignancy-associated anemia was
      the strongest predictor of non-cardiac death (57% vs. 4% in non-anemic patients,
      P<0.001). Anemia of chronic disease neither predicted cardiac nor non-cardiac
      death. CONCLUSIONS: To the authors' knowledge, this is the first study to show
      that iron-deficiency anemia is a strong predictor of cardiac death when compared
      to patients with other types of anemia or to non-anemic patients.

PMID- 20145591
TI  - Feasibility of transradial approach in a hub and spoke cath lab network.
AB  - AIM: Radial artery approach for coronary angiography presents advantages in terms
      of reduction of costs and complications. Opening a diagnostic-only cath lab is
      controversial in an era of interventional approach. The authors present the data
      of Carpi diagnostic-only cath lab (Spoke), satellite of the main cath lab
      situated in Modena (Hub) 20 Kms apart. METHODS: Between January 2004 and December
      2007, 1496 coronary angiograms were performed. The indication was ischemic heart
      disease in 1197 cases (80%), dilated cardiomiopathy in other 165 cases (11%) and
      valvular heart disease in the remaining 134 patients (9%). The procedure was
      performed percutaneously via radial artery in 95% (N=1421) of the cases, via
      brachial artery in 1% (N=15) and via femoral artery in the remaining 4% (N=60) of
      patients. RESULTS: Among the 1197 patients undergoing coronary angiography for
      ischemic heart disease, an indication to medical therapy was given in 443 (37%),
      a surgical indication in 216 (18%) patients and an indication to percutaneous
      coronary intervention (PCI) in 538 (45%) cases. PCI was performed in the Hub
      centre the same day and via the same arterial approach of the diagnostic
      angiography, maintaining the sheath in situ during transport. In 6 patients only
      it was necessary to shift to a femoral approach. CONCLUSIONS: This model presents
      many advantages: 1) a cath lab in a peripheral hospital allows a early carrying
      out of the hemodynamic examination with reduction of hospital stay; 2) transport
      to the Hub centre cath lab is undertaken only in patients who really need PCI; 3)
      the PCI is feasible the same day of the diagnostic examination; 4) this model
      relieves the hub centre congestion, ensuring motivation and professional
      competence for personnel of peripheral hospital.

PMID- 20145592
TI  - Diagnostic criteria for apical ballooning derived from quantitative analysis of
      left ventricular angiograms.
AB  - AIM: The aim of this study was to evaluate diagnostic criteria for apical
      ballooning (AB) derived from quantitative analysis of left ventricular
      angiograms. AB is an unusual cause of left ventricular dysfunction mimicking
      acute transmural ischemia (STEMI). METHODS: This study compared the systolic and
      diastolic linear measures of left ventricle (LV) of ten consecutive patients with
      AB to those obtained in a control group of STEMI patients. These measures allowed
      the calculation of the systolic shortening of the long and short axis of the LV.
      RESULTS: Systolic short axis and long axis shortening are significantly different
      in the two groups, so that both the systolic and diastolic sphericity indexes
      (SI) were much lower in AB patients (diastolic SI: 1.62+/-0.18 vs. 1.81+/-0.16;
      P=0.026 and systolic SI: 1.58+/-0.22 and 2.48+/-0.54 P<0.001). Moreover, a long
      axis shortening >0.6 cm was 100% sensitive and specific for AB. CONCLUSIONS: This
      study demonstrated that AB can be differentiated from STEMI by means of imple
      parameters of LV motion with a high degree of sensitivity and specificity.

PMID- 20145593
TI  - Repeat adverse events long after percutaneous coronary revascularization in
      diabetics.
AB  - AIM: Diabetics with coronary artery disease face a high risk of adverse events
      following coronary revascularization. However, recurrence rates of after the
      first revascularization have never been appraised. The aim of this study was to
      evaluate recurrent events in diabetics undergoing percutaneous coronary
      intervention (PCI) in the current era. METHODS: Authors collected baseline and
      outcome data of consecutive type-2 diabetics treated with PCI (July 2002-December
      2005) . End-points of interest were the long-term rates of major adverse cardiac
      events (MACE: cardiac death, myocardial infarction [MI], percutaneous target
      vessel revascularization [TVR-PCI], or coronary artery bypass grafting [CABG]),
      non-TVR PCI, and stent thrombosis. RESULTS: A total of 429 diabetics were
      included, 191 (44%) insulin-dependent, with drug-eluting stents implanted in 232
      (54%). After a median of 38 months, events were as follows: MACE in 167 (38.9%)
      subjects, cardiac death in 38 (8.8%), MI in 42 (9.8%), TVR-PCI in 130 (30.3%),
      CABG in 11 (2.6%), non-TVR-PCI in 52 (12.1%), and definite stent thrombosis in 9
      (2.1%). Among the 129 patients undergoing TVR-PCI as first event, as many as 28
      (21.7%) underwent a second TVR-PCI, 7 (5.4%) underwent a third TVR-PCI, and a
      further 2 (1.5%) underwent a fourth TVR-PCI, whereas CABG was performed in 2
      (1.5%) and non-TVR-PCI in 4 (3.1%). CONCLUSIONS: This work, originally reporting
      on the risk of recurrent repeat revascularization events among diabetics treated
      with PCI, showed that adverse events occur frequently in these patients, but can
      be managed in most cases safely and successfully by means of repeat PCI only.

PMID- 20145594
TI  - Use of NaCl saline hydration and N-Acetyl Cysteine to prevent contrast induced
      nephropathy in different populations of patients at high and low risk undergoing
      coronary artery angiography.
AB  - AIM: Contrast-induced nephropathy (CIN) is most commonly defined as acute renal
      failure occurring within 48-72 h of exposure to intravascular radiographic
      contrast medium that is not attributable to other causes. In international
      literature a 25% increase in serum creatinine levels or an increase in absolute
      values of 0.5 mg/dL from baseline has been suggested to define CIN. The reported
      incidence of CIN varies widely, ranging from 2% to 50%. This variability results
      from differences in the presence or absence of risk factors. With a retrospective
      analysis authors evaluated the use of NaCl saline hydration and N-acetyl cysteine
      (NAC) to prevent CIN in different populations of patients at high and low risk
      undergoing coronary artery angiography. METHODS: From January 2007 to December
      2008, 597 patients underwent coronary artery angiography with a low osmolarity
      contrast agent. Nephrotoxic drugs such as diuretics, metformin, ACE-I and ARBs
      were stopped at least 24 h before the procedure. The population was divided into
      two groups: group A (high risk 342 patients, 57.2%) identified for the presence
      of at least one risk factor such as diabetes, age >65 years, baseline creatinine
      >1.4 mg/dL and group B (low risk 255 patients, 42.8%) for the absence of any of
      the risk mentioned above. Only group A was treated with a saline hydration (1
      mL/kg/h) plus NAC 600 mg 12 h before and 12 h after the procedure. RESULTS: The
      overall incidence of CIN was 6.7% (40 patients). In particular, the incidence of
      CIN was 4.4% (15 patients) in the group A and 9.8% (25 patients) in the group B
      respectively (P=0.017). Interestingly, the Contrast Index (volume
      administrated/theoretical maximum volume) was significantly lower in group B
      (P<0.005). In the multivariate analysis, including risk factors such as age,
      diabetes, hypertension, hypercholesterol-mia, current smoke, baseline creatinine
      level, Contrast Index and hydration, the last variable was the only one inversely
      correlated independently with the incidence of CIN (P=0.001). CONCLUSIONS: The
      hydration with saline and NAC is an effective and low-cost tool in preventing CIN
      in patients undergoing coronary artery angiography and, according to the current
      guidelines, should be used in all high-risk patients. Present results show that
      even in patients at low risk for CIN, hydration could be useful: in fact, despite
      the Contrast Index was significantly lower in this population, the incidence of
      CIN was greater, thus suggesting a potential role for hydration also in the low
      risk population.

PMID- 20145595
TI  - Coronary chronic total occlusion.
AB  - Percutaneous coronary intervention (PCI) for chronic total occlusions (CTO)
      remains a major challenge in interventional cardiology. Successful recanalization
      of a CTO can alleviate angina, reduce the need for coronary artery bypass surgery
      and increase long-term survival. Improving results from the historically quoted
      success rates of 50% to the levels now routinely quoted by some operators (80
      90%), requires not just skill and experience, but also a thorough understanding
      of the wide array of materials and techniques now available in this area. The
      decision to attempt PCI of a CTO (versus continued medical therapy or surgical
      revascularization) requires an individualized risk/benefit analysis, encompassing
      clinical, imaging and technical considerations.

PMID- 20145596
TI  - Intravascular ultrasound and drug-eluting stents. Where are we now?
AB  - Drug-eluting stents (DES) have revolutionized interventional cardiology. The
      profound ability of DES to suppress neointimal hyperplasia results in a reduced
      need for revascularization and improved clinical outcomes. DES, however, are not
      immune to in-stent restenosis. This problem particularly affects DES implanted
      for "off-label" indications and in challenging clinical and anatomic scenarios.
      In addition, as compared to bare-metal stents, DES do not reduce the incidence of
      stent thrombosis. Therefore, optimization of DES deployment is becoming
      increasingly important and, in this regard, intravascular ultrasound (IVUS)
      provides unique insights. IVUS assessment of neointimal growth has been of major
      value to understand the mechanisms of action of DES and also to compare different
      DES. Notably, IVUS enables optimization of DES implantation. DES underexpansion,
      edge-restenosis, residual dissections, plaque prolapse, stent fracture,
      incomplete stent apposition and DES-related aneurysms, are readily assessed by
      IVUS. The use of IVUS to study and manage DES failures (namely in-stent
      restenosis and DES thrombosis) is of major value. In conclusion, IVUS provides
      unique insights during DES implantation, allows DES optimization and should
      always be used during the management of DES failures: in-stent restenosis and DES
      thrombosis.

PMID- 20145597
TI  - Interventional treatment of congenital heart disease patients.
AB  - During the last 10 years the interventional treatment of congenital and
      structural heart diseases has known enormous changes in techniques, methods and
      patients management. Lesions previously treated surgically are now approached in
      the catheterization laboratory. The advent of multidisciplinary approach of
      congenital heart disease has made possible the development of hybrid techniques,
      of fetal medicine and of magnetic resonance imaging (MRI)- guided cardiac
      catheterization. Technological innovation has introduced new concepts in
      treatment of congenital heart disease patients and has allowed to adapt different
      techniques to single patients. The knowledge of the evolution of structural heart
      disease has allowed to chose the best percutaneous and/ or surgical technique and
      the best materials to optimize long term results. Improvement in non invasive
      imaging modality has allowed to diminish the radiation exposure and to provide
      useful information to interventional cardiologists and cardiac surgeons.
      Absorbable, drug eluting tools will change the treatment and probably the natural
      history of congenital and structural cardiac and vascular diseases.

PMID- 20145598
TI  - Carotid endovascular interventions: patient selection, devices, techniques and
      tips.
AB  - The optimal treatment of patients with asymptomatic or symptomatic carotid artery
      disease (CAD) has been a long-lasting debate. The choice between carotid
      endarterectomy (CEA), carotid artery stenting (CAS) and/or optimal medical
      therapy to treat patients with CAD, depends on their risk profile. Recent data
      from EVA-3S, SPACE randomized trials failed to demonstrate non-inferiority for
      CAS over CEA. However, other publications suggest that with growing experience
      and the development of dedicated CAS technology, CAS can be performed safely and
      efficiently. The success of carotid stenting does not solely depend on the
      operator's skills and experience, but also on the adequate selection of carotid
      stents and cerebral protection devices. Currently, CAS practitioners are
      confronted with a large number of dedicated CAS devices (stents and embolic
      protection devices). This wide array of products makes individual treatment
      strategies difficult to generalise as no single device possesses all of the
      optimal features to treat all types of carotid plaques and patients. This article
      reviews the principles of patient selection and device selection in contemporary
      CAS practice.

PMID- 20145600
TI  - Stem cells in cardiac repair in an inflammatory microenvironment.
AB  - Despite advances in clinical interventions, drug therapy and preventative
      strategies for cardiovascular disease, heart disease remains the number one cause
      of death in the United States. A major cause of heart failure leading to death is
      myocardial ischemic disease. Terminal heart failure can be salvaged in some cases
      by cardiac transplants, but this therapeutic approach is limited by lack of
      supply, high cost, and problems with immunosuppression. An attractive alternative
      approach proposed over the last 1-2 decades is the replacement of myocardium at
      the level of the myocyte, which has focused on stem cell therapy. This form of
      therapy has been successful for hematopoietic replacement. Similar therapy has
      been proposed to treat hearts ravaged by ischemic necrosis and apoptosis.
      However, the experimental studies have not been effectively translated to
      patients with myocardial infarction or heart failure. This review discusses the
      current literature and points out key studies that are required for future
      directions, focusing on key roles for microenvironmental factors, such as
      cytokines, in stem cells responses when placed at sites of cardiac injuries. In
      the case of mesenchymal stem cells (MSCs), they exert both immune- enhancer and 
      suppressor functions, which are referred to as immune plasticity. This type of
      immune properties by MSCs is significant to therapeutic outcomes. Thus, the
      plasticity of MSCs, with regards to immune responses, has to be considered
      carefully in tissue repair and replacement and in gene delivery systems. The
      route by which cytokines are delivered as adjuvant to cell therapy, or as methods
      to mobilize stem cells, will show varied results, depending on the degree of
      injury, underlying clinical disorders and other diverse parameters, such as
      ethnicity, age and genomic profile. In addition to MSCs, roles exist for other
      stem cells, such as those from placenta, cord blood, hematopoietic
      stem/progenitor cells and cardiac stem cells.

PMID- 20145599
TI  - Tips and tricks in renal artery angioplasty and stenting: angiography, stent
      placement, embolic protection, complications, and contrast induced nephropathy.
AB  - Patient selection and a thorough understanding of the technical aspects of
      percutaneous transluminal renal artery stent placement (PTRS) are paramount to
      obtaining optimal outcomes. The purpose of this paper is to review renal artery
      angiography and stent placement techniques. Tips and tricks for successful
      procedural outcome are described. The potential role of embolic protection
      devices is discussed and practices for avoiding complications including contrast
      induced nephropathy are reviewed.

PMID- 20145601
TI  - Coronary stenting early before non-cardiac surgery: is the endothelial progenitor
      cell capturing coronary stent a solution?
AB  - The authors report, for the first time, immediate and mid-term outcome of early
      antiplatelet therapy discontinuation followed by uneventful non-cardiac surgery
      and endovascular aortic repair, few days after successful deployment of an
      endothelial progenitor cell capturing coronary stent, in three consecutive
      patients.

PMID- 20145602
TI  - Unmasked myocardial bridge after coronary stenting.

PMID- 20145603
TI  - Subvalvular aortic stenosis.

PMID- 20145604
TI  - Preparation of Drosophila polytene chromosome squashes for antibody labeling.
AB  - Drosophila has long been a favorite model system for studying the relationship
      between chromatin structure and gene regulation due to the cytological advantages
      provided by the giant salivary gland polytene chromosomes of third instar larvae.
      In this tissue the chromosomes undergo many rounds of replication in the absence
      of cell division giving rise to approximately 1000 copies. The DNA remains
      aligned after each replicative cycle resulting in greatly enlarged chromosomes
      that provide a unique opportunity to correlate chromatin morphology with the
      localization of specific proteins. Consequently, there has been a high level of
      interest in defining the epigenetic modifications present at different genes and
      at different stages of the transcription process. An important tool for such
      studies is the labeling of polytene chromosomes with antibodies to the enzyme,
      transcription factor, or histone modification of interest. This video protocol
      illustrates the squash technique used in the Johansen laboratory to prepare
      Drosophila polytene chromosomes for antibody labeling.

PMID- 20145606
TI  - Nutritional status and growth in pediatric Crohn's disease: a population-based
      study.
AB  - OBJECTIVES: Growth retardation and malnutrition are major features of pediatric
      Crohn's disease (CD). We examined nutritional and growth parameters from
      diagnosis to maximal follow-up in a population-based pediatric cohort, and we
      determined predictive factors. METHODS: A total of 261 patients (156 boys, 105
      girls) with onset of CD before the age of 17 were identified from 1988 to 2004
      through the EPIMAD registry (Registre des Maladies Inflammatoires Chroniques de
      l'Intestin) in northern France. Median age at diagnosis was 13 years (11.2-15.4)
      and median follow-up was 73 months (46-114). Z-scores of height/age, weight/age,
      and body mass index (BMI)/age were determined. Multivariate stepwise regression
      analysis identified predictive factors for malnutrition and growth retardation at
      maximal follow-up. RESULTS: At diagnosis, 25 children (9.5%) showed height less
      than -2 s.d., 70 (27%) weight less than -2 s.d., and 84 (32%) BMI less than -2
      s.d. At maximal follow-up, growth retardation was present in 18 children (6.9%),
      whereas 40 (15%) had malnutrition. Nutritional status was more severely impaired
      in children with stricturing disease. Growth and nutritional retardation at
      diagnosis, young age, male gender, and extraintestinal manifestations at
      diagnosis were indicators of poor prognosis. A significant compensation was
      observed for weight and BMI in both genders and for height in girls. No treatment
      was associated with height, weight, or BMI at maximal follow-up. CONCLUSIONS: In
      our pediatric population-based study, growth retardation and severe malnutrition
      were still present at maximal follow-up in 6.9 and 15% of CD children,
      respectively. Young boys with substantial inflammatory manifestations of CD have
      a higher risk of subsequent growth failure, especially when growth retardation is
      present at diagnosis.

PMID- 20145605
TI  - TLR9 and IRF3 cooperate to induce a systemic inflammatory response in mice
      injected with liposome:DNA.
AB  - Liposome:DNA is a promising gene therapy vector. However, this vector can elicit
      a systemic inflammatory response syndrome (SIRS). Prior reports indicate that
      liposome:DNA vectors activate Toll-like receptor (TLR)9. We hypothesized that
      liposome:DNA vectors also activate the cytosolic DNA-sensing pathway, which
      signals via interferon (IFN) regulatory factor (IRF)3. To test this, we treated
      dendritic cells (DCs) with liposome:DNA in vitro and found that IRF3 was
      phosphorylated independent of TLR9. To test the contribution of this pathway in
      vivo, we injected a liposome:DNA vector into wild-type (WT), TLR9-knockout (KO),
      IRF3-KO, and TLR9-IRF3-double-KO (DKO) mice. WT mice exhibited a systemic
      inflammatory response, evidenced by elevations in serum cytokines, serum enzyme
      changes indicating organ damage, hypothermia, and mortality. The cytokine
      response was reduced in TLR9-KO, IRF3-KO, and TLR9-IRF3-DKO mice and all three
      groups survived. We found that IFN-gamma-KO mice that receive liposome:DNA had a
      reduced cytokine response and 100% survival. CD11c(+) and NK1.1(+) cells produced
      IFN-gamma and depleting CD11c(+) cells reduced the cytokine response in mice
      injected with liposome:DNA. These findings may facilitate the development of
      immunologically inert gene therapy vectors and may provide general insight into
      the mechanisms of SIRS.

PMID- 20145607
TI  - Mucosal recovery and mortality in adults with celiac disease after treatment with
      a gluten-free diet.
AB  - OBJECTIVES: Clinical response is typically observed in most adults with celiac
      disease (CD) after treatment with a gluten-free diet (GFD). The rate of mucosal
      recovery is less certain. The aims of this study were (1) to estimate the rate of
      mucosal recovery after GFD in a cohort of adults with CD, and (2) to assess the
      clinical implications of persistent mucosal damage after GFD. METHODS: The study
      group included adults with biopsy-proven CD evaluated at the Mayo Clinic who had
      duodenal biopsies at diagnosis and at least one follow-up intestinal biopsy to
      assess mucosal recovery after starting a GFD. The primary outcomes of interest
      were mucosal recovery and all-cause mortality. RESULTS: Of 381 adults with biopsy
      proven CD, 241 (73% women) had both a diagnostic and follow-up biopsy available
      for re-review. Among these 241, the Kaplan-Meier rate of confirmed mucosal
      recovery at 2 years following diagnosis was 34% (95% confidence interval (CI): 27
      40%), and at 5 years was 66% (95% CI: 58-74%). Most patients (82%) had some
      clinical response to GFD, but it was not a reliable marker of mucosal recovery
      (P=0.7). Serological response was associated with confirmed mucosal recovery
      (P=0.01). Poor compliance to GFD (P<0.01), severe CD defined by diarrhea and
      weight loss (P<0.001), and total villous atrophy at diagnosis (P<0.001) were
      strongly associated with persistent mucosal damage. There was a trend toward an
      association between achievement of mucosal recovery and a reduced rate of all
      cause mortality (hazard ratio=0.13, 95% CI: 0.02-1.06, P=0.06), adjusted for
      gender and age. CONCLUSIONS: Mucosal recovery was absent in a substantial portion
      of adults with CD after treatment with a GFD. There was a borderline significant
      association between confirmed mucosal recovery (vs. persistent damage) and
      reduced mortality independent of age and gender. Systematic follow-up with
      intestinal biopsies may be advisable in patients diagnosed with CD as adults.

PMID- 20145608
TI  - Dose-response efficacy of a proprietary probiotic formula of Lactobacillus
      acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated
      diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult
      patients.
AB  - OBJECTIVES: Standard therapies for antibiotic-associated diarrhea (AAD) and
      Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic
      prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.
      METHODS: In this single-center, randomized, double-blind, placebo-controlled dose
      ranging study, we randomized 255 adult inpatients to one of three groups: two
      probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo
      capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each
      probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus
      acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic
      prophylaxis began within 36 h of initial antibiotic administration, continued for
      5 days after the last antibiotic dose, and patients were followed for an
      additional 21 days. RESULTS: Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1
      (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In
      patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter
      symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD
      incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs.
      placebo (23.8%). Gastrointestinal symptoms were less common in the treatment
      groups vs. placebo and in Pro-2 vs. Pro-1. CONCLUSIONS: The proprietary probiotic
      blend used in this study was well tolerated and effective for reducing risk of
      AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose
      ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and
      fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov
      number NCT00958308).

PMID- 20145609
TI  - Nonalcoholic fatty liver disease increases risk of death among patients with
      diabetes: a community-based cohort study.
AB  - OBJECTIVES: The significance of nonalcoholic fatty liver disease (NAFLD) among
      patients with diabetes is unknown. We sought to determine whether a diagnosis of
      NAFLD influenced mortality among a community-based cohort of patients with type
      II diabetes mellitus. METHODS: A total of 337 residents of Olmsted County,
      Minnesota with diabetes mellitus diagnosed between 1980 and 2000 were identified
      using the Rochester Epidemiology Project and the Mayo Laboratory Information
      System, and followed for 10.9 + or - 5.2 years (range 0.1-25). Survival was
      analyzed using Cox proportional hazards modeling, with NAFLD treated as a time
      dependent covariate. RESULTS: Among the 337 residents, 116 were diagnosed with
      NAFLD 0.9 + or - 4.6 years after diabetes diagnosis. Patients with NAFLD were
      younger, and more likely to be female and obese. Overall, 99/337 (29%) patients
      died. In multivariate analysis to adjust for confounders, overall mortality was
      significantly associated with a diagnosis of NAFLD (hazard ratio (HR) 2.2; 95%
      confidence interval (CI) 1.1, 4.2; P=0.03), presence of ischemic heart disease
      (HR 2.3; 95% CI 1.2, 4.4), and duration of diabetes (HR per 1 year, 1.1; 95% CI
      1.03, 1.2). The most common causes of death in the NAFLD cohort were malignancy
      (33% of deaths), liver-related complications (19% of deaths), and ischemic heart
      disease (19% of deaths). In adjusted multivariate models, NAFLD was borderline
      associated with an increased risk of dying from malignancy (HR 2.3; 95% CI 0.9,
      5.9; P=0.09) and not from cardiovascular disease (HR 0.9; 95% CI 0.3, 2.4;
      P=0.81). CONCLUSIONS: The diagnosis of NAFLD is associated with an increased risk
      of overall death among patients with diabetes mellitus.

PMID- 20145610
TI  - Clinical utility of measuring infliximab and human anti-chimeric antibody
      concentrations in patients with inflammatory bowel disease.
AB  - OBJECTIVES: Human anti-chimeric antibodies (HACAs) and subtherapeutic infliximab
      concentrations are associated with decreased duration of response. We evaluated
      the clinical utility of measuring HACA and infliximab concentrations. METHODS:
      The medical records of patients with inflammatory bowel disease (IBD) who had
      HACA and infliximab concentrations measured were reviewed to determine whether
      the result affected clinical management. RESULTS: One hundred fifty-five patients
      had HACA and infliximab concentrations measured. The main indications for testing
      were loss of response to infliximab (49%), partial response after initiation of
      infliximab (22%), and possible autoimmune/delayed hypersensitivity reaction
      (10%). HACAs were identified in 35 patients (23%) and therapeutic infliximab
      concentrations in 51 patients (33%). Of 177 tests assessed, the results impacted
      treatment decisions in 73%. In HACA-positive patients, change to another anti
      tumor necrosis factor (TNF) agent was associated with a complete or partial
      response in 92% of patients, whereas dose escalation had a response of 17%. In
      patients with subtherapeutic infliximab concentrations, dose escalation was
      associated with complete or partial clinical response in 86% of patients whereas
      changing to another anti-TNF agent had a response of 33%. Patients with clinical
      symptoms and therapeutic infliximab concentrations were continued at the same
      dose 76% of the time and had no evidence of active inflammation by
      endoscopic/radiographic assessment 62% of the time. CONCLUSIONS: Measurement of
      HACA and infliximab concentration impacts management and is clinically useful.
      Increasing the infliximab dose in patients who have HACAs is ineffective, whereas
      in patients with subtherapeutic infliximab concentrations, this strategy may be a
      good alternative to changing to another anti-TNF agent.

PMID- 20145611
TI  - Distribution of HPV types associated with cervical cancers in Scotland and
      implications for the impact of HPV vaccines.
AB  - BACKGROUND/METHODS: This study evaluated human papillomavirus (HPV) type
      prevalence in 370 Scottish invasive cervical cancers (ICCs) using HPV genotyping
      and HPV mRNA detection. RESULTS: HPV 16 and/or 18 was detected in 72% of cancers
      overall and in 82% of HPV-positive cancers. HPV 45 and 16 were the most
      frequently transcribed types. CONCLUSION: A significant reduction in ICC in
      Scotland should be achieved through the HPV immunisation programme.

PMID- 20145612
TI  - Factors that contribute to faecal cyclooxygenase-2 mRNA expression in subjects
      with colorectal cancer.
AB  - BACKGROUND: We previously reported that a faecal cyclooxygenase-2 (COX-2) mRNA
      assay was useful for identifying colorectal cancer (CRC). This study sought to
      investigate the factors that contribute to faecal COX-2 mRNA expression in
      subjects with CRC. METHODS: The study cohort comprised 78 patients with CRC and
      36 control subjects. The expressions of COX-2, beta-2-microglobulin (B2M),
      carcinoembryonic antigen (CEA), E-cadherin (E-cad), and CD45 mRNA in faeces and
      COX-2 mRNA expression in tissue were determined by quantitative real-time RT-PCR.
      RESULTS: The level of faecal expression of COX-2 mRNA in CRC was significantly
      higher than that in controls. A significant correlation was found between faecal
      COX-2 mRNA expression and faecal B2M, CEA, E-cad, or CD45 mRNAs, markers of
      exfoliated total cells, colonocytes, and leukocytes, respectively. A significant
      correlation was found between the expression of COX-2 mRNA in faeces and tumour
      surface area, COX-2 mRNA expression in primary tumour. There was no difference in
      faecal COX-2 mRNA expression between proximal CRC and distal CRC. CONCLUSION: COX
      2 mRNA expression in faeces seems to originate from tumour lesion and to be
      affected by factors such as the number of exfoliated cells, exfoliation of
      inflammatory cells, COX-2 mRNA expression in tumour, and tumour size.

PMID- 20145613
TI  - Establishment and characterization of a new hypoxia-resistant cancer cell line,
      OCUM-12/Hypo, derived from a scirrhous gastric carcinoma.
AB  - BACKGROUND: Many kinds of solid tumour have heterogeneously a hypoxic
      environment. Tumour hypoxia reported to be associated with more aggressive tumour
      phenotypes such as high metastatic ability and resistance to various anti-cancer
      therapies which may lead to a poorer prognosis. However, the mechanisms by which
      hypoxia affects the aggressive phenotypes remain unclear. METHODS: We established
      a scirrhous gastric carcinoma cell line (OCUM-12) from ascites associated with
      scirrhous gastric carcinoma, and a hypoxia-resistant cancer cell line (OCUM
      12/Hypo) was cloned from OCUM-12 cells by continuous exposure to 1% oxygen.
      RESULTS: Histologic findings from orthotopic tumours derived from parent OCUM-12
      cells and daughter OCUM-12/Hypo cells revealed poorly differentiated
      adenocarcinoma with extensive fibrosis that resembled human scirrhous gastric
      cancer. Necrotic lesions were frequently detected in the OCUM-12 tumours but were
      rarely found in the OCUM-12/Hypo tumours, although both types had multiple
      hypoxic loci. Apoptosis rate of OCUM-12 cells was increased to 24.7% at 1% O(2),
      whereas that of OCUM-12/Hypo was 5.6%. The OCUM-12/Hypo orthotopic models
      developed multiple metastases to the peritoneum and lymph nodes, but the OCUM-12
      models did not. OCUM-12/Hypo cells showed epithelial-to-mesenchymal transition
      and high migratory and invasive activities in comparison with OCUM-12 cells. The
      mRNA expression levels of both E-cadherin and zonula occludens ZO-1 and ZO-2
      decreased in OCUM-12/Hypo cells, and that of vimentin, Snail-1, Slug/Snail-2,
      Twist, ZEB-1, ZEB-2, matrix metalloproteinase-1 (MMP-1), and MMP-2 were increased
      in OCUM-12/Hypo cells. CONCLUSION: OCUM-12 and OCUM-12/Hypo may be useful for the
      elucidation of disease progression associated with scirrhous gastric cancer in
      the setting of chronic hypoxia.

PMID- 20145614
TI  - Side-population cells in luminal-type breast cancer have tumour-initiating cell
      properties, and are regulated by HER2 expression and signalling.
AB  - BACKGROUND: The expression of side-population (SP) cells and their relation to
      tumour-initiating cells (T-ICs) have been insufficiently studied in breast cancer
      (BC). We therefore evaluated primary cell cultures derived from patients and a
      panel of human BC cell lines with luminal- or basal-molecular signatures for the
      presence of SP and BC stem cell markers. METHODS: The SPs from luminal-type BC
      were analysed for BC T-IC characteristics, including human epidermal growth
      factor receptor 2 (HER2), ERalpha, IGFBP7 expression and their ability to
      initiate tumours in non-obese diabetic severe combined immunodeficiency
      (NOD/SCID) mice. Pharmacological modulators were used to assess the effects of
      HER2 signalling and breast cancer-resistance protein (BCRP) expression on SPs.
      RESULTS: The SP was more prevalent in the luminal subtype of BC compared with the
      basal subtype. HER2 expression was significantly correlated with the occurrence
      of an SP (r(2)=0.75, P=0.0003). Disappearance of SP in the presence of Ko143, a
      specific inhibitor of the ATP-binding cassette transporter BCRP, suggests that
      BCRP is the predominant transporter expressed in this population. The SP also
      decreased in the presence of HER2 signalling inhibitors AG825 or trastuzumab,
      strengthening the notion that HER2 contributed to the SP phenotype, likely
      through downstream AKT signalling. The SP cells from luminal-type MCF-7 cells
      with enforced expression of HER2, and primary cells with luminal-like properties
      from a BC patient, displayed enrichment in cells capable of repopulating tumours
      in NOD/SCID mice. Engraftment of SP cells was inhibited by pretreatment with
      AG825 or by in vivo treatment with trastuzumab. INTERPRETATION: Our findings
      indicate an important role of HER2 in regulating SP and hence T-ICs in BC, which
      may account for the poor responsiveness of HER2-positive BCs to chemotherapy, as
      well as their aggressiveness.

PMID- 20145615
TI  - High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals
      correlates with poor prognosis in colorectal cancer.
AB  - BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to
      have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4
      signalling in colon tumourigenesis, we examined the expression of TLR4 and
      myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS:
      The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal
      mucosae was evaluated by immunohistochemistry, and the correlations between their
      immunoscores and clinicopathological variables, including disease-free survival
      (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal
      mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23%
      cancers showed high expression of MyD88. The high expression of TLR4 and MyD88
      was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In
      univariate analysis, the high expression of TLR4 was significantly associated
      with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15
      4.07; P=0.015). The high expression of MyD88 expression was significantly
      associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31-4.13; P=0.0038 and HR:
      3.03; 95% CI: 1.67-5.48; P=0.0002). The high combined expression of TLR4 and
      MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI:
      1.27-3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64-5.38; P=0.0003). Multivariate
      analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI:
      0.99-3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01-3.67;
      P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17-4.33; P=0.0112) were independent
      prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was
      strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest
      that high expression of TLR4 and MyD88 is associated with liver metastasis and is
      an independent predictor of poor prognosis in patients with CRC.

PMID- 20145616
TI  - The role of zinc in the anti-tumour and anti-cachectic activity of D-myo-inositol
      1,2,6-triphosphate.
AB  - BACKGROUND: D-myo-inositol-1,2,6-triphosphate (alpha-trinositol, AT) is a
      polyanionic molecule capable of chelating divalent metal ions with anti-tumour
      and anti-cachectic activity in a murine model. METHODS: To investigate the role
      of zinc in this process, mice bearing cachexia-inducing MAC16 tumour were treated
      with AT, with or without concomitant administration of ZnSO(4). RESULTS: At a
      dose of 40 mg kg(-1), AT effectively attenuated both weight loss and growth of
      the MAC16 tumour, and both effects were attenuated by co-administration of
      Zn(2+). The concentration of zinc in gastrocnemius muscle increased with
      increasing weight loss, whereas administration of AT decreased the levels of zinc
      in plasma, skeletal muscle and tumour, which were restored back to control values
      after administration of ZnSO(4). CONCLUSION: These results suggest that zinc is
      important in both tumour growth and cachexia in this animal model.

PMID- 20145617
TI  - MEPE/OF45 as a new target for sensitizing human tumour cells to DNA damage
      inducers.
AB  - BACKGROUND: We recently identified matrix extracellular
      phosphoglycoprotein/osteoblast factor 45 (MEPE/OF45) as a new cofactor of CHK1 in
      rat cells. The aim of this study was to determine the role of human MEPE/OF45
      (hMEPE/OF45 has approximately 50% homology with rat MEPE/OF45 (rMEPE/OF45)) in
      affecting the sensitivity of human tumour cells to DNA damage. METHODS:
      hMEPE/OF45 expression in different human tumour cell lines and its relevance to
      the resistance of cell lines to DNA damage inducers such as ionising radiation
      (IR) or camptothecin (CPT) were assessed. Cells lines stably expressing wild-type
      MEPE/OF45 or mutant MEPE/OF45 (with the CHK1 interactive key domain (amino acids
      488-507) deleted) were established. Cell survival, G(2) accumulation, CHK1 half
      life and the CHK1 level in ligase 3 complexes were examined. RESULTS: hMEPE/OF45
      expression correlates with the resistance of cell lines to IR or CPT.
      Upregulating wild-type hMEPE/OF45 (but not mutant hMEPE/OF45) could stabilize
      CHK1 by reducing CHK1 interaction for its E3 ligases Cul1 or Cula4A; it increases
      the G(2) checkpoint response and increases the resistance of tumour cells to IR
      or CPT treatment. CONCLUSION: hMEPE/OF45 could be a new target for sensitizing
      tumour cells to radiotherapy or chemotherapy.

PMID- 20145618
TI  - Choi response criteria for early prediction of clinical outcome in patients with
      metastatic renal cell cancer treated with sunitinib.
AB  - BACKGROUND: Because sunitinib can induce extensive necrosis in metastatic renal
      cell cancer (mRCC), we examined whether criteria defined by Choi might be
      valuable to predict early sunitinib efficacy. METHODS: Computed tomography was
      used for measurement of tumour lesions in mm and lesion attenuation in Hounsfield
      units (HUs). According to Choi criteria partial response (PR) was defined as > or
      =10% decrease in size or > or =15% decrease in attenuation. RESULTS: A total of
      55 mRCC patients treated with sunitinib were included. At first evaluation,
      according to the Response Evaluation Criteria in Solid Tumours (RECIST) 7
      patients had PR, 38 stable disease (SD), and 10 progressive disease (PD), whereas
      according to Choi criteria 36 patients had PR, 6 SD and 13 PD. Median tumour
      attenuation decreased from 66 to 47 HUs (P< or =0.001). In patients with PR, Choi
      criteria had a significantly better predictive value for progression-free
      survival and overall survival (both Ps<0.001) than RECIST (P=0.685 and 0.191
      respectively). The predictive value for RECIST increased (P=0.001 and <0.001
      respectively), when best response during treatment was taken into account.
      CONCLUSION: Choi criteria could be helpful to define early mRCC patients who
      benefit from sunitinib, but the use of these criteria will not change the
      management of these patients.

PMID- 20145619
TI  - Hyponatremia as a prognostic and predictive factor in metastatic renal cell
      carcinoma.
AB  - BACKGROUND: Low serum sodium has recently been associated with poor survival in
      localised renal cell carcinoma (RCC). We now show the prognostic effect of serum
      sodium in patients with metastatic RCC (mRCC). METHODS: Cohort A comprised 120
      consecutive patients with mRCC receiving subcutaneous, low-dose interleukin-2 and
      interferon-alpha. Hyponatremia was assessed in univariate and multivariate
      analyses. An independent cohort of another 120 patients with mRCC was used for
      validation (cohort B). RESULTS: In cohort A, estimated 5-year survival was 15%
      and median survival was 15.1 months. Serum sodium ranged between 126 and 144 mM.
      Twenty-four patients (20%) had serum sodium levels below normal range (<136 mM).
      In multivariate analysis, significant independent risk factors for short survival
      were low serum sodium (P=0.014), high neutrophils (P=0.018), lactate
      dehydrogenase >1.5 upper normal level (P=0.002), and number of metastatic sites
      (+3) (P=0.003). In cohort B, serum sodium ranged between 128 and 146 mM.
      Seventeen patients (14%) had sodium levels below normal range. In multivariate
      analysis, serum sodium was validated as an independent prognostic factor
      (P=0.001). A significant association between lack of response and hyponatremia
      was observed in both cohorts (P=0.003 and P=0.02, respectively). CONCLUSION: Low
      serum sodium is a new, validated, independent prognostic, and predictive factor
      in patients with mRCC.

PMID- 20145620
TI  - Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue.
AB  - BACKGROUND: The prognosis of squamous cell carcinoma of the oral tongue is poor
      and it would be beneficial to find prognostic markers to better adjust treatment.
      Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription
      factor c-myc affects cell proliferation and apoptosis, and Snail regulates
      epithelial-mesenchymal transition. The expression of these markers has been
      connected to prognosis in many cancer types. METHODS: Bmi-1, c-myc, and Snail
      expressions were studied in our material consisting of 73 primarily T1N0M0 oral
      tongue carcinoma patients. We compared the immunoexpressions of Bmi-1, c-myc, and
      Snail with clinical parameters including the degree of histological
      differentiation, tumour size, TNM classification, depth of invasion, and
      resection margins. In addition, survival analyses were performed, comparing
      disease-free survival time with the registered protein expression of the markers
      mentioned above. RESULTS: A significant correlation between Bmi-1 protein
      expression and recurrence (log-rank test, P=0.005) was detected. Snail and c-myc
      expression did not correlate with prognosis. Snail expression correlated with
      histopathological grade (Fisher's exact test, P=0.007) and with the invasion
      depth of tumours (chi(2)-test, P=0.037). CONCLUSION: Negative Bmi-1
      immunoexpression might serve as a marker of poor prognosis in oral tongue
      carcinoma patients.

PMID- 20145621
TI  - Inhibitory effect of a TGFbeta receptor type-I inhibitor, Ki26894, on
      invasiveness of scirrhous gastric cancer cells.
AB  - BACKGROUND: Gastric cancer cells frequently metastasise, partly because of their
      highly invasive nature. Transforming growth factor-beta (TGF-beta) receptor
      signalling is closely associated with the invasion of cancer cells. The aim of
      this study was to clarify the effect of a TGF-beta receptor (TbetaR)
      phosphorylation inhibitor on the invasiveness of gastric cancer cells. METHODS:
      Four gastric cancer cell lines, including two scirrhous-type cell lines and two
      non-scirrhous-type cell lines, were used. A TbetaR type I (TbetaR-I) kinase
      inhibitor, Ki26894, inhibits the phosphorylation of Smad2 at an ATP-binding site
      of TbetaR-I. We investigated the expression levels of TbetaR and phospho-Smad2,
      and the effects of TGF-beta in the presence or absence of Ki26894 on Smad2
      phosphorylation, invasion, migration, epithelial-to-mesenchymal transition (EMT),
      Ras homologue gene family member A (RhoA), ZO-2, myosin, and E-cadherin
      expression of gastric cancer cells. RESULTS: TbetaR-I, TbetaR-II, and phospho
      Smad2 expressions were found in scirrhous gastric cancer cells, but not in non
      scirrhous gastric cancer cells. Ki26894 decreased Smad2 phosphorylation induced
      by TGF-beta1 in scirrhous gastric cancer cells. Transforming growth factor-beta1
      upregulated the invasion, migration, and EMT ability of scirrhous gastric cancer
      cells. Transforming growth factor-beta1 significantly upregulated the activity of
      RhoA and myosin phosphorylation, whereas TGF-beta1 decreased ZO-2 and E-cadherin
      expression in scirrhous gastric cancer cells. Interestingly, Ki26894 inhibited
      these characteristics in scirrhous gastric cancer cells. In contrast, non
      scirrhous gastric cancer cells were not affected by TGF-beta1 or Ki26894
      treatment. CONCLUSION: A TbetaR-I kinase inhibitor decreases the invasiveness and
      EMT of scirrhous gastric cancer cells. Ki26894 is therefore considered to be a
      promising therapeutic compound for the metastasis of scirrhous gastric carcinoma.

PMID- 20145622
TI  - Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic
      activity on papillary thyroid cancer expressing TPO.
AB  - BACKGROUND: Thyroid cancers are difficult to treat due to their limited
      responsiveness to chemo- and radiotherapy. There is thus a great interest in and
      a need for alternative therapeutic approaches. RESULTS: We studied the cytotoxic
      activity of anti-thyroperoxidase autoantibodies (anti-TPO aAbs, expressed in
      baculovirus/insect cell (B4) and CHO cells (B4') or purified from patients' sera)
      against a papillary thyroid cancer (NPA) cell line. Anti-TPO aAbs from patients'
      sera led to a partial destruction of NPA cell line by complement-dependent
      cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) and
      exhibited an anti-proliferative activity. Comparison of the cytotoxic activity of
      anti-TPO aAbs shows that B4' induced an anti-proliferative effect and a better
      ADCC than B4, but a lower one than anti-TPO aAbs from patients' sera. Antibody
      dependent cell-mediated cytotoxicity was increased when human peripheral blood
      mononuclear cells were used as effector cells, suggesting that FcgammaRs, CD64,
      CD32 and CD16 are involved. Indeed, anti-TPO aAbs from patients' sera, but not B4
      and B4', exhibited CDC activity. CONCLUSIONS: These data indicate that anti-TPO
      aAbs display moderate ADCC and anti-proliferative activities on NPA cells; IgG
      glycosylation appears to be important for cytotoxic activity and ADCC efficiency
      depends on FcgammaR-bearing cells. Finally, recombinant human anti-TPO aAbs
      cannot yet be considered as an optimal tool for the development of a novel
      therapeutic approach for thyroid cancer.

PMID- 20145623
TI  - The neuroscience of human intelligence differences.
AB  - Neuroscience is contributing to an understanding of the biological bases of human
      intelligence differences. This work is principally being conducted along two
      empirical fronts: genetics--quantitative and molecular--and brain imaging.
      Quantitative genetic studies have established that there are additive genetic
      contributions to different aspects of cognitive ability--especially general
      intelligence--and how they change through the lifespan. Molecular genetic studies
      have yet to identify reliably reproducible contributions from individual genes.
      Structural and functional brain-imaging studies have identified differences in
      brain pathways, especially parieto-frontal pathways, that contribute to
      intelligence differences. There is also evidence that brain efficiency correlates
      positively with intelligence.

PMID- 20145624
TI  - Olfactory signalling in vertebrates and insects: differences and commonalities.
AB  - Vertebrates and insects have evolved complex repertoires of chemosensory
      receptors to detect and distinguish odours. With a few exceptions, vertebrate
      chemosensory receptors belong to the family of G protein-coupled receptors that
      initiate a cascade of cellular signalling events and thereby electrically excite
      the neuron. Insect receptors, which are structurally and genetically unrelated to
      vertebrate receptors, are a complex of two distinct molecules that serves both as
      a receptor for the odorant and as an ion channel that is gated by binding of the
      odorant. Metabotropic signalling in vertebrates provides a rich panoply of
      positive and negative regulation, whereas ionotropic signalling in insects
      enhances processing speed.

PMID- 20145625
TI  - Can a modest exercise program really improve physical functioning and quality of
      life among recipients of hematopoietic SCT?

PMID- 20145627
TI  - Abstracts from Haematopoietic Stem Cell Transplantation for Severe Autoimmune
      Diseases. Florence, Italy. November 19-20, 2009.

PMID- 20145629
TI  - Report from Durham.

PMID- 20145631
TI  - Does pre-existing diabetes affect prostate cancer prognosis? A systematic review.
AB  - To summarize the influence of pre-existing diabetes on mortality and morbidity in
      men with prostate cancer. We searched MEDLINE and EMBASE from inception through 1
      October 2008. Search terms were related to diabetes, cancer and prognosis.
      Studies were included if they reported an original data analysis of prostate
      cancer prognosis, compared outcomes between men with and without diabetes and
      were in English. Titles, abstracts and articles were reviewed independently by
      two authors. Conflicts were settled by consensus or third review. We abstracted
      data on study design, analytic methods, outcomes and quality. We summarized
      mortality and morbidity outcomes qualitatively and conducted a preliminary meta
      analysis to quantify the risk of long-term (>3 months), overall mortality. In
      total, 11 articles were included in the review. Overall, one of four studies
      found increased prostate cancer mortality, one of two studies found increased
      nonprostate cancer mortality and one study found increased 30-day mortality. Data
      from four studies could be included in a preliminary meta-analysis for long-term,
      overall mortality and produced a pooled hazard ratio of 1.57 (95% CI: 1.12-2.20).
      Diabetes was also associated with receiving radiation therapy, complication
      rates, recurrence and treatment failure. Our analysis suggests that pre-existing
      diabetes affects the treatment and outcomes of men with prostate cancer.

PMID- 20145633
TI  - An animal model for the treatment of Alzheimer's disease: potential for a new
      direction in therapies that enhance the epigenic mechanisms of memory formation.

PMID- 20145632
TI  - Allosteric antipsychotics: m4 muscarinic potentiators as novel treatments for
      schizophrenia.

PMID- 20145638
TI  - Mastocytosis in children is associated with mutations in c-KIT.

PMID- 20145640
TI  - Defining the antigen determinant for T-cell-mediated contact dermatitis using p
      phenylenediamine: a gateway to chemical immunology.
AB  - By binding to host proteins to form haptens, low-molecular-weight compounds such
      as p-phenylenediamine (PPD) can become contact sensitizers. In this issue,
      Jenkinson et al. demonstrate that it is possible to use chemically characterized
      hapten-protein complexes to analyze T-cell responses in cells from allergic
      individuals. This approach may help in the development of in vitro tests for
      diagnosing contact dermatitis.

PMID- 20145641
TI  - Multiple genes and locus interactions in susceptibility to vitiligo.
AB  - Refining the position of loci on chromosomes 7 and 9 previously linked with
      generalized vitiligo or vitiligo-associated autoimmune diseases presenting in
      families has been performed by high-density single-nucleotide polymorphism (SNP)
      genotyping. Investigation of the genetic interaction among these loci (and with a
      previously identified susceptibility gene, NLRP1, on chromosome 17) as risk
      factors for vitiligo demonstrates the complex nature of this disease.

PMID- 20145642
TI  - NADPH:quinone oxidoreductase-1 as a new regulatory enzyme that increases melanin
      synthesis.
AB  - Most hypopigmenting reagents target the inhibition of tyrosinase, the key enzyme
      involved in melanin synthesis. In this issue, Choi et al. report that
      NADPH:quinone oxidoreductase-1 (NQO1) increases melanin synthesis, probably via
      the suppression of tyrosinase degradation. Because NQO1 was identified by
      comparing normally pigmented melanocytes with hypopigmented acral lentiginous
      melanoma cells, these results suggest various hypotheses regarding the
      carcinogenic origin of the latter.

PMID- 20145643
TI  - KIT masters mast cells in kids, too.
AB  - Adult mastocytosis is usually persistent and caused by c-KIT codon 816-activating
      mutations. Pediatric mastocytosis is often transient, and the molecular mechanism
      driving mast cell proliferation in pediatric cases remains unclear. In this
      issue, Bodemer et al. report novel c-KIT mutations in a large percentage of
      pediatric cases, identifying both similarities and fundamental differences in the
      mechanisms causing adult and pediatric mastocytosis.

PMID- 20145644
TI  - It is better to flush than to break under pressure.
AB  - In this issue Fromy et al. describe alterations in pressure-induced vasodilation
      in the populations most prone to development of pressure ulcers of the skin.
      Advancing our understanding regarding the basic pathophysiological mechanisms
      mediating the development of pressure ulcers will allow for better delineation of
      populations at risk. This study provides novel insights into this important and
      poorly understood entity, using tools that are potentially deployable into
      clinical practice.

PMID- 20145653
TI  - Dynamic metabolic response to multiple spreading depolarizations in patients with
      acute brain injury: an online microdialysis study.
AB  - Spreading depolarizations (SDs) occur spontaneously with high incidence in
      patients with acute brain injury. They can be detected by subdural
      electrocorticographic recordings. We here characterize the dynamic metabolic
      response to these events. A microdialysis catheter was inserted into perilesional
      cortical tissue adjacent to a strip for electrocorticography following craniotomy
      in 10 patients. The microdialysis catheter was connected to an online
      microdialysis assay measuring glucose and lactate concentrations every 30 to 60
      secs. Spontaneously occurring SDs systematically caused a reduction in dialysate
      glucose by -32.0 micromol/L (range: -92.3 to -18.4 micromol/L, n=90) and increase
      in lactate by +23.1 micromol/L (range: +5.5 to +93.6 micromol/L, n=49). The
      changes were sustained at 20 mins after the SD events and highly significant
      using an area under the curve analysis (P<0.0001). Multiple and frequent SDs led
      to a progressive stepwise depletion of brain glucose. Hence, SD events cause a
      massive energy imbalance and their frequent occurrence leads to a local
      insufficiency of glucose supply. Such a failure would compromise cellular
      repolarization and hence tissue viability. The findings offer a new mechanism to
      account for otherwise unexplained instances of depletion of brain microdialysate
      glucose.

PMID- 20145654
TI  - Oxygen-sensitive outcomes and gene expression in acute ischemic stroke.
AB  - Acute ischemic stroke (AIS) results in focal deprivation of blood-borne factors,
      one of them being oxygen. The purpose of this study was two-fold: (1) to identify
      therapeutic conditions for supplemental oxygen in AIS and (2) to use
      transcriptome-wide screening toward uncovering oxygen-sensitive mechanisms.
      Transient MCAO in rodents was used to delineate the therapeutic potential of
      normobaric (NBO, 100% O(2), 1ATA) and hyperbaric oxygen (HBO, 100% O(2), 2ATA)
      during ischemia (iNBO, iHBO) and after reperfusion (rNBO, rHBO). Stroke lesion
      was quantified using 4.7 T MRI at 48 h. Supplemental oxygen during AIS
      significantly attenuated percent stroke hemisphere lesion volume as compared with
      that in room air (RA) controls, whereas identical treatment immediately after
      reperfusion exacerbated lesion volume (RA=22.4+/-1.8, iNBO=9.9+/-3.6, iHBO=6.6+/
      4.8, rNBO=29.8+/-3.6, rHBO=35.4+/-7.6). iNBO and iHBO corrected penumbra tissue
      pO(2) during AIS as measured by EPR oxymetry. Unbiased query of oxygen-sensitive
      transcriptome in stroke-affected tissue identified 5,769 differentially expressed
      genes. Candidate genes were verified by real-time PCR using neurons laser
      captured from the stroke-affected somatosensory cortex. Directed microarray
      analysis showed that supplemental oxygen limited leukocyte accumulation to the
      infarct site by attenuation of stroke-inducible proinflammatory chemokine
      response. The findings provide key information relevant to understanding oxygen
      dependent molecular mechanisms in the AIS-affected brain.

PMID- 20145655
TI  - Mechanisms contributing to cerebral infarct size after stroke: gender,
      reperfusion, T lymphocytes, and Nox2-derived superoxide.
AB  - Cerebral infarct volume is typically smaller in premenopausal females than in age
      matched males after ischemic stroke, but the underlying mechanisms are poorly
      understood. In this study we provide evidence in mice that this gender difference
      only occurs when the ischemic brain is reperfused. The limited tissue salvage
      achieved by reperfusion in male mice is associated with increased expression of
      proinflammatory proteins, including cyclooxygenase-2 (Cox-2), Nox2, and vascular
      cell adhesion molecule-1 (VCAM-1), and infiltration of Nox2-containing T
      lymphocytes into the infarcted brain, whereas such changes are minimal in female
      mice after ischemia-reperfusion (I-R). Infarct volume after I-R was no greater at
      72 h than at 24 h in either gender. Infarct development was Nox2 dependent in
      male but not in female mice, and Nox2 within the infarct was predominantly
      localized in T lymphocytes. Stroke resulted in an approximately 15-fold increase
      in Nox2-dependent superoxide production by circulating, but not spleen-derived, T
      lymphocytes in male mice, and this was approximately sevenfold greater than in
      female mice. These circulating immune cells may thus represent a major and
      previously unrecognized source of superoxide in the acutely ischemic and
      reperfused brain of males (and potentially in postmenopausal females). Our
      findings provide novel insights into mechanisms that could be therapeutically
      targeted in acute ischemic stroke patients who receive thrombolysis therapy to
      induce cerebral reperfusion.

PMID- 20145656
TI  - Absolute arterial cerebral blood volume quantification using inflow vascular
      space-occupancy with dynamic subtraction magnetic resonance imaging.
AB  - In patients with steno-occlusive disease of the internal carotid artery (ICA),
      cerebral blood flow may be maintained by autoregulatory increases in arterial
      cerebral blood volume (aCBV). Therefore, characterizing aCBV may be useful for
      understanding hemodynamic compensation strategies. A new 'inflow vascular-space
      occupancy with dynamic subtraction (iVASO-DS)' MRI approach is presented where
      aCBV (mL blood/100 mL parenchyma) is quantified without contrast agents using the
      difference between images with and without inflowing blood water signal. The
      iVASO-DS contrast mechanism is investigated (3.0 T, spatial resolution=2.4 x 2.4
      x 5 mm(3)) in healthy volunteers (n=8; age=29+/-5 years), and patients with mild
      (n=7; age=72+/-8 years) and severe (n=10; age=73+/-8 years) ICA stenoses. aCBV
      was quantified in right and left hemispheres in controls, and, alongside industry
      standard dynamic susceptibility contrast (DSC), contralateral (cont), and
      ipsilateral (ips) to maximum stenosis in patients. iVASO contrast significantly
      correlated (R=0.67, P<0.01) with DSC-CBV after accounting for transit time
      discrepancies. Gray matter aCBV (mL/100 mL) was 1.60+/-0.10 (right) versus 1.61+/
      0.20 (left) in controls, 1.59+/-0.38 (cont) and 1.65+/-0.37 (ips) in mild
      stenosis patients, and 1.72+/-0.18 (cont) and 1.58+/-0.20 (ips) in severe
      stenosis patients. aCBV was asymmetric (P<0.01) in 41% of patients whereas no
      asymmetry was found in any control. The potential of iVASO-DS for autoregulation
      studies is discussed in the context of existing hemodynamic literature.

PMID- 20145657
TI  - Cerebral blood volume alterations in the perilesional areas in the rat brain
      after traumatic brain injury--comparison with behavioral outcome.
AB  - In the traumatic brain injury (TBI) the initial impact causes both primary
      injury, and launches secondary injury cascades. One consequence, and a factor
      that may contribute to these secondary changes and functional outcome, is altered
      hemodynamics. The relative cerebral blood volume (CBV) changes in rat brain after
      severe controlled cortical impact injury were characterized to assess their
      interrelations with motor function impairment. Magnetic resonance imaging (MRI)
      was performed 1, 2, 4 h, and 1, 2, 3, 4, 7, and 14 days after TBI to quantify CBV
      and water diffusion. Neuroscore test was conducted before, and 2, 7, and 14 days
      after the TBI. We found distinct temporal profile of CBV in the perilesional
      area, hippocampus, and in the primary lesion. In all regions, the first response
      was drop of CBV. Perifocal CBV was reduced for over 4 days thereafter gradually
      recovering. After the initial drop, the hippocampal CBV was increased for 2
      weeks. Neuroscore demonstrated severely impaired motor functions 2 days after
      injury (33% decrease), which then slowly recovered in 2 weeks. This recovery
      parallelled the recovery of perifocal CBV. CBV MRI can detect cerebrovascular
      pathophysiology after TBI in the vulnerable perilesional area, which seems to
      potentially associate with time course of sensory-motor deficit.

PMID- 20145658
TI  - Activation of NR2A receptors induces ischemic tolerance through CREB signaling.
AB  - Previous exposure to a nonlethal ischemic insult protects the brain against
      subsequent harmful ischemia. N-methyl-D-aspartate (NMDA) receptors are a highly
      studied target of neuroprotection after ischemia. Recently, NMDA receptor
      subtypes were implicated in neuronal survival and death. We focused on the
      contribution of NR2A and cyclic-AMP response element (CRE)-binding protein (CREB)
      signaling to ischemic tolerance using primary cortical neurons. Ischemia in vitro
      was modeled by oxygen-glucose deprivation (OGD). Ischemic tolerance was induced
      by applying 45-mins OGD 24 h before 180-mins OGD. Sublethal OGD also induced
      cross-tolerance against lethal glutamate and hydrogen peroxide. After sublethal
      OGD, expression of phosphorylated CREB and CRE transcriptional activity were
      significantly increased. When CRE activity was inhibited by CREB-S133A, a mutant
      CREB, ischemic tolerance was abolished. Inhibiting NR2A using NVP-AAM077
      attenuated preconditioning-induced neuroprotection and correlated with decreased
      CRE activity levels. Activating NR2A using bicuculline and 4-aminopiridine
      induced resistance to lethal ischemia accompanied by elevated CRE activity
      levels, and this effect was abolished by NVP-AAM077. Elevated brain-derived
      neurotrophic factor (BDNF) transcriptional activities were observed after
      sublethal OGD and administration of bicuculline and 4-aminopiridine. NR2A
      containing NMDA receptors and CREB signaling have important functions in the
      induction of ischemic tolerance. This may provide potential novel therapeutic
      strategies to treat ischemic stroke.

PMID- 20145659
TI  - G-CSF administration is neuroprotective following transient cerebral ischemia
      even in the absence of a functional NOS-2 gene.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a candidate neuroprotective
      factor following cerebral ischemia. To determine whether G-CSF acts partly
      through the inhibition of nitric oxide synthase (NOS)-2 expression, we
      administered G-CSF to male NOS-2-/- mice after cerebral ischemia. Although male
      NOS-2-/- mice exhibit resistance to the gross effects of cerebral ischemia, they
      display neuronal loss and skilled motor deficits following cerebral ischemia.
      Administration of G-CSF during reperfusion reduced motor deficit and neuronal
      loss. Thus, G-CSF is still effective in NOS-2 gene-deficient mice, suggesting
      that part of the mechanism of action is independent of NOS-2.

PMID- 20145660
TI  - Kidney cancer: neoadjuvant targeted therapies in renal cell carcinoma.

PMID- 20145661
TI  - Prostatitis: predictive value of post-massage urine leukocyte count for AIP.

PMID- 20145662
TI  - Pediatrics: combining antimuscarinics shows promise for overactive bladder.

PMID- 20145663
TI  - Renal medullary-like carcinoma in an adult without sickle cell hemoglobinopathy.
AB  - BACKGROUND: A 42-year-old white man with no significant prior medical history
      presented with macroscopic hematuria of 2 months' duration. His family history
      was notable for a maternal grandfather with kidney cancer. INVESTIGATIONS:
      Urinalysis, CT, microscopic examination of tumor, immunohistochemical analysis of
      tumor, hemoglobin electrophoresis, molecular cytogenetic analysis, gene
      sequencing. DIAGNOSIS: Renal medullary-like carcinoma in an adult without sickle
      cell trait, sickle cell disease or other hemoglobinopathies. MANAGEMENT: The
      patient underwent laparoscopic nephrectomy to remove the tumor and received
      adjuvant sorafenib (400 mg per day) as part of the E2805 ASSURE (Adjuvant
      Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) trial. Metastatic
      recurrence of the tumor occurred 9 months after nephrectomy, for which the
      patient underwent tumor debulking and retroperitoneal lymph node dissection,
      followed by chemotherapy consisting of gemcitabine (2,000 mg/m(2)) and
      doxorubicin (50 mg/m(2)), both given on day 1 of a 14-day cycle. After six cycles
      of drug treatment, the patient had achieved a partial response. The patient was
      managed by active surveillance for 4 months, when he developed further symptoms
      and disease progression was detected. Third-line systemic therapy in the form of
      21-day cycles of cisplatin (80 mg/m(2) on day 1) and etoposide (100 mg/m(2) on
      days 1-3) has recently been initiated.

PMID- 20145664
TI  - 'Educational symposium on long-term results of large prospective clinical trials
      for childhood acute lymphoblastic leukemia (1985-2000)'.

PMID- 20145666
TI  - Long-term intervention with Lactobacillus helveticus fermented milk reduces
      augmentation index in hypertensive subjects.
AB  - BACKGROUND: The milk casein-derived biologically active tripeptides, isoleucyl
      prolyl-proline (Ile-Pro-Pro) and valyl-prolyl-proline (Val-Pro-Pro), have
      documented antihypertensive effect probably related to reduced angiotensin
      formation. It has been suggested that these tripeptides may reduce arterial
      stiffness and improve endothelial function. Our aim was to evaluate whether the
      milk-based drink containing Ile-Pro-Pro and Val-Pro-Pro influence arterial
      stiffness, measured as augmentation index (AIx), and endothelial function in man.
      METHODS: In a double-blind parallel group intervention study, 89 hypertensive
      subjects received daily peptide milk containing a low dose of tripeptides (5
      mg/day) for 12 weeks and a high dose (50 mg/day) for the following 12 weeks, or a
      placebo milk drink to titrate the dose-response effect. Arterial stiffness was
      assessed by pulse wave analysis at the beginning and end of each intervention
      period. Endothelial function was tested by examining pulse wave reflection
      response to sublingual nitroglycerin and salbutamol inhalation. Blood pressure
      was measured by using office and 24-h ambulatory blood pressure measurement.
      RESULTS: At the end of the second intervention period, AIx decreased
      significantly in the peptide group compared with the placebo group (peptide group
      -1.53% (95% confidence interval (CI) -2.95 to -0.12), placebo group 1.20% (95% CI
      0.09-2.32), P=0.013). No change in endothelial function index was observed
      (peptide group 0.02 (95% CI -0.06 to 0.08), placebo group 0.04 (95% CI -0.04 to
      0.12), P=0.85). There were no statistically significant differences between the
      effects of the peptide and placebo treatment on office and 24-h ambulatory blood
      pressure. CONCLUSIONS: Long-term treatment with Lactobacillus helveticus
      fermented milk containing bioactive peptides reduces arterial stiffness expressed
      as AIx in hypertensive subjects.

PMID- 20145667
TI  - Effect of age, gender and calciotropic hormones on the relationship between
      vitamin D receptor gene polymorphisms and bone mineral density.
AB  - BACKGROUND/OBJECTIVES: Hypovitaminosis D is a major public health problem
      worldwide and unexpectedly more so in sunny countries. Vitamin D receptor (VDR)
      gene is associated with inter-individual variance in bone mineral density (BMD).
      Studies assessing the effect of VDR gene polymorphisms on BMD yielded conflicting
      results. The aim of this study was to assess the relationship between VDR
      polymorphisms and BMD in the Lebanese, across age groups and genders and to
      assess the effect of PTH and lean mass and vitamin D levels on such relationship.
      SUBJECTS/METHODS: In total, 203 subjects aged 65-85 years and 336 children aged
      10-17 years. Polymorphisms in the VDR gene were assessed with the restriction
      enzymes BsmI, TaqI and ApaI. Bone mineral content, BMD and lean mass were
      measured using Dual-Energy X-ray Absorptiometry (DXA). The dominant hand strength
      was measured in children. RESULTS: Heterozygote genotype was the most frequent in
      both age groups. There was no difference in the frequency distribution of
      genotypes between the young and the elderly. No relationship between VDR
      genotypes and lean mass was found in either age group. Heterozygote boys had the
      lowest parathormone (PTH) and heterozygote elderly women had the highest BMD at
      the spine and forearm. CONCLUSIONS: In the Lebanese, the relationship between VDR
      polymorphisms and BMD differs by age. Survival does not seem to differ by VDR
      genotype. However, further studies are needed to assess the effect of VDR gene
      polymorphisms on mortality per se and time to mortality, not evaluated in this
      study.

PMID- 20145668
TI  - Mito-nuclear discordance in the degree of population differentiation in a marine
      goby.
AB  - An increasing number of phylogeographic studies on marine species shows
      discordant patterns in the degree of population differentiation between nuclear
      and mitochondrial markers. To understand better which factors have the potential
      to cause these patterns of discordance in marine organisms, a population genetic
      study was realized on the sand goby Pomatoschistus minutus (Pallas 1770;
      Gobiidae, Teleostei). Sand gobies from eight European locations were genotyped at
      eight microsatellite markers. Microsatellites confirmed the global
      phylogeographical pattern of P. minutus observed with mitochondrial DNA (mtDNA)
      markers and nuclear allozyme markers. Three groups consistent with the
      mitochondrial lineages were defined (the Mediterranean, Iberian and North
      Atlantic groups) and indications of a recent founder event in the northern Baltic
      Sea were found. Nevertheless, differences in the degree of population
      differentiation between the nuclear and mitochondrial markers were large (global
      F(ST)-values for microsatellites=0.0121; for allozymes=0.00831; for
      mtDNA=0.4293). Selection, sex-biased dispersal, homoplasy and a high effective
      population size are generally accepted as explanations for this mitonuclear
      discrepancy in the degree of population differentiation. In this study, selection
      on mtDNA and microsatellites, male-biased dispersal and homoplasy on
      microsatellite markers are unlikely to be a main cause for this discrepancy. The
      most likely reason for the discordant pattern is a recent demographical expansion
      of the sand goby, resulting in high effective population sizes slowing down the
      differentiation of nuclear DNA.

PMID- 20145669
TI  - Variation explained in mixed-model association mapping.
AB  - Genomic mapping of complex traits across species demands integrating genetics and
      statistics. In particular, because it is easily interpreted, the R(2) statistic
      is commonly used in quantitative trait locus (QTL) mapping studies to measure the
      proportion of phenotypic variation explained by molecular markers. Mixed models
      with random polygenic effects have been used in complex trait dissection in
      different species. However, unlike fixed linear regression models, linear mixed
      models have no well-established R(2) statistic for assessing goodness-of-fit and
      prediction power. Our objectives were to assess the performance of several R(2)
      like statistics for a linear mixed model in association mapping and to identify
      any such statistic that measures model-data agreement and provides an intuitive
      indication of QTL effect. Our results showed that the likelihood-ratio-based R(2)
      (R(LR)(2)) satisfies several critical requirements proposed for the R(2)-like
      statistic. As R(LR)(2) reduces to the regular R(2) for fixed models without
      random effects other than residual, it provides a general measure for the effect
      of QTL in mixed-model association mapping. Moreover, we found that R(LR)(2) can
      help explain the overlap between overall population structure modeled as fixed
      effects and relative kinship modeled though random effects. As both approaches
      are derived from molecular marker information and are not mutually exclusive,
      comparing R(LR)(2) values from different models provides a logical bridge between
      statistical analysis and underlying genetics of complex traits.

PMID- 20145670
TI  - Heritable artificial sex chromosomes in medaka: a leap towards real-time
      observation of sex chromosome evolution.

PMID- 20145671
TI  - Genetic basis of incidence and period length of circadian rhythm for locomotor
      activity in populations of a seed beetle.
AB  - Circadian rhythms are ubiquitous in a wide variety of organisms, although their
      genetic variation has been analyzed in only a few species. We found genetic
      differences in the circadian rhythm of adult locomotor activity among strains of
      the adzuki bean beetle, Callosobruchus chinensis, which differed in origin and
      have been maintained in isolation. All beetles in some strains clearly had free
      running rhythms in constant darkness whereas most beetles in other strains were
      arrhythmic. The period of free-running rhythm varied from approximately 19 to 23
      h between the strains. F(1) males from reciprocal crosses among strains with
      different periods of circadian rhythms had circadian periods that were
      intermediate between their parental strains. Segregation of the circadian rhythm
      appeared in the F(2) generation. These findings are consistent with the
      hypothesis that variation in the period length of circadian rhythm is explained
      by a major autosomal gene with additive effects and no dominance. This hypothesis
      was supported by the joint scaling test for the free-running period in the F(1)
      and F(2) generations. We discuss possible causes for genetic variation in
      circadian rhythm in the C. chinensis strains in terms of random factors and
      selection.

PMID- 20145672
TI  - Bateman (1948): pioneer in the measurement of sexual selection.

PMID- 20145673
TI  - Expression quantitative trait loci analysis of genes in porcine muscle by
      quantitative real-time RT-PCR compared to microarray data.
AB  - Genetic analysis of transcriptional profiling is a promising approach for
      identifying biological pathways and dissecting the genetics of complex traits.
      Here, we report on expression quantitative trait loci (eQTL) that were estimated
      from the quantitative real-time RT-PCR data of 276 F(2) animals and compared with
      eQTL identified using 74 microarrays. In total, 13 genes were selected that
      showed trait-dependent expression in microarray experiments and exhibited 21
      eQTL. Real-time RT-PCR and microarray data revealed seven cis eQTL in total, of
      which one was only detected by real-time RT-PCR, one was only detected by
      microarray analysis, three were consistently found in overlapping intervals and
      two were in neighbouring intervals on the same chromosome; whereas no trans eQTL
      was confirmed. We demonstrate that cis regulation is a stable characteristic of
      individual transcripts. Consequently, a global microarray eQTL analysis of a
      limited number of samples can be used for exploring functional and regulatory
      gene networks and scanning for cis eQTL, whereas the subsequent analysis of a
      subset of likely cis-regulated genes by real-time RT-PCR in a larger number of
      samples is relevant to narrow down a QTL region by targeting these positional
      candidate genes. In fact, when modelling SNPs of six genes as fixed effects in
      the eQTL analysis, eQTL peaks were shifted downwards, experimentally confirming
      the impact of the respective polymorphic genes, although these SNPs were not
      located in the regulatory sequence and these shifts occur as a result of linkage
      disequilibrium in the F(2) population.

PMID- 20145674
TI  - Clinical utility gene card for: Ehlers-Danlos syndrome types I-VII.

PMID- 20145675
TI  - The USH2A c.2299delG mutation: dating its common origin in a Southern European
      population.
AB  - Usher syndrome type II is the most common form of Usher syndrome. USH2A is the
      main responsible gene of the three known to be disease causing. It encodes two
      isoforms of the protein usherin. This protein is part of an interactome that has
      an essential role in the development and function of inner ear hair cells and
      photoreceptors. The gene contains 72 exons spanning over a region of 800 kb.
      Although numerous mutations have been described, the c.2299delG mutation is the
      most prevalent in several populations. Its ancestral origin was previously
      suggested after the identification of a common core haplotype restricted to 250
      kb in the 5' region that encodes the short usherin isoform. By extending the
      haplotype analysis over the 800 kb region of the USH2A gene with a total of 14
      intragenic single nucleotide polymorphisms, we have been able to define 10
      different c.2299delG haplotypes, showing high variability but preserving the
      previously described core haplotype. An exhaustive c.2299delG/control haplotype
      study suggests that the major source of variability in the USH2A gene is
      recombination. Furthermore, we have evidenced twice the amount of recombination
      hotspots located in the 500 kb region that covers the 3' end of the gene,
      explaining the higher variability observed in this region when compared with the
      250 kb of the 5' region. Our data confirm the common ancestral origin of the
      c.2299delG mutation.

PMID- 20145677
TI  - Evidence for CTLA4 as a susceptibility gene for dilated cardiomyopathy.
AB  - The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed
      on activated T cells with downregulatory properties. The aim of this study was to
      analyse whether single-nucleotide polymorphisms (SNPs) within the CTLA4 gene are
      associated with the diagnosis and disease course of dilated cardiomyopathy (DCM).
      In two independent cohorts of DCM patients (n=251 and 223) and healthy controls
      (n=591), the promoter and all four exons of the CTLA4 gene, including their
      flanking regions, were genotyped, and the resulting allele and genotype
      distributions of the identified SNPs were compared between the groups. We
      confirmed two known SNPs in the promoter region (-318C>T) and in exon 1
      (+49A>G;Thr17Ala). The allelic frequencies and genotypic distribution of the
      promoter SNP were similar for DCM patients compared with controls. However, the
      G/G genotype of the Thr17Ala variant was significantly more frequent in DCM
      patients compared with controls (37 out of 251 patients (14.7%) versus 44 out of
      591 controls (7.4%), P=0.005). The higher frequency of the G/G genotype was
      confirmed in an additional DCM cohort (29 out of 223 patients (13.0%), P=0.039),
      indicating that this SNP functions as a risk factor for DCM. At follow-up after 1
      year, the ejection fraction and the end-diastolic diameter of the left ventricle
      did not differ significantly between DCM patients carrying the G/G genotype
      versus other genotypes (n=199). Our data indicate that the common CTLA4 variant,
      Thr17Ala, confers susceptibility for DCM, but does not seem to influence the
      course of the disease 1 year after diagnosis.

PMID- 20145676
TI  - Therapeutic exon skipping for dysferlinopathies?
AB  - Antisense-mediated exon skipping is a promising therapeutic approach for Duchenne
      muscular dystrophy (DMD) currently tested in clinical trials. The aim is to
      reframe dystrophin transcripts using antisense oligonucleotides (AONs). These
      hide an exon from the splicing machinery to induce exon skipping, restoration of
      the reading frame and generation of internally deleted, but partially functional
      proteins. It thus relies on the characteristic of the dystrophin protein, which
      has essential N- and C-terminal domains, whereas the central rod domain is
      largely redundant. This approach may also be applicable to limb-girdle muscular
      dystrophy type 2B (LGMD2B), Myoshi myopathy (MM) and distal myopathy with
      anterior tibial onset (DMAT), which are caused by mutations in the dysferlin
      encoding DYSF gene. Dysferlin has a function in repairing muscle membrane damage.
      Dysferlin contains calcium-dependent C2 lipid binding (C2) domains and an
      essential transmembrane domain. However, mildly affected patients in whom one or
      a large number of DYSF exons were missing have been described, suggesting that
      internally deleted dysferlin proteins can be functional. Thus, exon skipping
      might also be applicable as a LGMD2B, MM and DMAT therapy. In this study we have
      analyzed the dysferlin protein domains and DYSF mutations and have described what
      exons are promising targets with regard to applicability and feasibility. We also
      show that DYSF exon skipping seems to be as straightforward as DMD exon skipping,
      as AONs to induce efficient skipping of four DYSF exons were readily identified.

PMID- 20145678
TI  - Mammary-digital-nail (MDN) syndrome: a novel phenotype maps to human chromosome
      22q12.3-13.1.
AB  - Mammary-digital-nail syndrome is a novel phenotypic association consisting of
      anonychia onychodystrophy with hypoplasia or absence of distal phalanges in males
      and females, accompanied by juvenile hypertrophy of the breast in affected
      females. This newly described genetic trait presents an autosomal dominant
      inheritance pattern, with either reduced penetrance or germ-line mosaicism.
      Analysis of the pedigree, linkage studies followed by a genome-wide screen and by
      haplotype analysis defined the locus for the phenotype within a 12 cM (4.3 Mb)
      interval on chromosome 22q12.3-13.1. This chromosomal region has not been
      implicated before in genetic disorders of the mammary tissue or limbs. These data
      suggest a possibly novel signaling pathway affecting the organogenesis of limbs
      and mammary glands in humans.

PMID- 20145679
TI  - An assessment of the exposure of Americans to perfluorooctane sulfonate: a
      comparison of estimated intake with values inferred from NHANES data.
AB  - To better understand human exposure to perfluorinated compounds (PFCs), a model
      that assesses exposure to perfluorooctane sulfonate (PFOS) and its precursors
      from both an intake and a body burden perspective and combines the two with a
      simple pharmacokinetic (PK) model is demonstrated. Exposure pathways were modeled
      under "typical" and "contaminated" scenarios, for young children and adults. A
      range of intakes was also estimated from serum concentrations of PFOS reported in
      the National Health and Nutrition Examination Survey (NHANES) using a first-order
      1-compartment PK model. Total PFOS intakes (medians summed over all pathways)
      were estimated as: 160 and 2200 ng/day for adults and 50 and 640 ng/day for
      children under typical and contaminated scenarios, respectively. Food ingestion
      appears to be the primary route of exposure in the general population. For
      children, the contribution from dust ingestion is nearly as great as from food
      ingestion. Pathway-specific contributions span several orders of magnitude and
      exhibit considerable overlap. PK modeling suggests central tendency PFOS intakes
      for adults range between 1.6 and 24.2 ng/kg-bw/day, and the forward-based intake
      estimates are within this range. The favorable comparison reported between the
      forward-modeled and the back-calculated range of intake predictions lends
      validity to the proposed framework.

PMID- 20145680
TI  - Medical image. An unexpected embolus revealed in transoesophageal echocardiogram.

PMID- 20145681
TI  - In utero brain damage from alcohol: a preventable tragedy.

PMID- 20145682
TI  - Hazardous drinking: not just an issue for the minority of drinkers.

PMID- 20145683
TI  - Obesity and gestational diabetes mellitus: breaking the cycle.

PMID- 20145684
TI  - Maternal alcohol use before and during pregnancy among women in Taranaki, New
      Zealand.
AB  - AIMS: The study researched alcohol consumption and drinking patterns before and
      during pregnancy. METHOD: This was a 1 month self report survey of postnatal
      women from 21 May-22 June 2006. A multiple choice questionnaire was handed out to
      them on the first or second postnatal day. RESULTS: There were a total of 117
      deliveries. The questionnaire was completed by 100 of the 104 women who received
      it. Before pregnancy, 80% of women reported drinking alcohol; 66% binge drinking.
      Twenty-eight percent continued consuming alcohol throughout pregnancy. The
      majority did reduce or stop their alcohol consumption, 7% however did not. Ten
      percent were drinking more than 2 units per typical day and more than 7 units per
      week during pregnancy. Four percent was drinking a lot more than this. Nine
      percent of the total cohort reported binge drinking during pregnancy. CONCLUSION:
      Just over a quarter of women drink alcohol throughout pregnancy. A significant
      minority of women drink relatively heavily (more than 4 units per occasion and
      multiple times per week) during pregnancy. Many women do reduce their alcohol use
      because of the pregnancy, but often only after they become aware of it. In New
      Zealand there is a real risk of fetal alcohol spectrum disorders.

PMID- 20145685
TI  - Pregnancy following gastric bypass surgery: what is the expected course and
      outcome?
AB  - AIM: To examine the course of pregnancy, labour, and the neonatal period in a
      group of women who have become pregnant following gastric bypass surgery for
      severe obesity. METHODS: Women who had experienced pregnancy following gastric
      bypass surgery were identified by an initial questionnaire. A second
      questionnaire was sent to those identified by the first questionnaire, who were
      willing to provide details concerning such pregnancies. RESULTS: Seventeen women
      experienced a total of 24 pregnancies and 25 live births. Five had experienced
      difficulties with conception or pregnancy prior to surgery. The average maternal
      weight gain was 6.13 kg. No major problems with fetal growth were observed.
      Babies were delivered at a mean gestational age of 37.5 weeks and with a mean
      birth weight of 3038 g. Six women reported a complication during pregnancy (25%)
      and five a complication in labour (20%). Two babies born to the same mother had
      congenital abnormalities attributable to a rare genetic disorder. CONCLUSION: The
      course of pregnancy and labour appears normalised for severely obese women
      following gastric bypass surgery. The weight loss and marked reduction in food
      intake following gastric bypass surgery does not lead to growth or development
      problems for offspring. Careful monitoring of expectant mothers who have
      undergone gastric bypass surgery is nevertheless to be recommended.

PMID- 20145686
TI  - Radiotherapy utilisation in lung cancer in New Zealand: disparities with optimal
      rates explained.
AB  - BACKGROUND AND PURPOSE: The intervention rate (IR) of radiotherapy (RT) is
      important for health service planning. As actual IRs are commonly lower than
      those predicted by models, we sought to determine the reasons for this
      discrepancy, using lung cancer in a mixed urban-rural region of New Zealand (NZ).
      METHODS: The appropriate utilisation of RT was calculated as the sum of the
      actual utilisation 3 years post diagnosis (88% of cases deceased), the estimated
      utilisation of the 12% remaining alive, and the percentage of cases that may have
      benefited from RT but did not receive it. RESULTS: The actual utilisation was
      estimated as 43% (range 40-48%). A further 8% of deceased cases may have
      benefitted from RT (but were not referred), giving an appropriate utilisation of
      51%. An additional 3.5% that may have benefitted from RT declined management. The
      difference from modelled IRs was due to a combination of early mortality, refusal
      of treatment and assumed higher RT treatment rates for many clinical scenarios.
      CONCLUSION: The appropriate utilisation of RT was substantially lower than IRs
      derived from models. The assumptions from which these models were derived may
      result in over-estimates for resource planning purposes.

PMID- 20145687
TI  - Prevalence of Raynaud's phenomenon in the adult New Zealand population.
AB  - AIMS: To estimate the prevalence of Raynaud's phenomenon (RP) in the New Zealand
      adult population. METHODS: 350 adults 18 years and over, random selected from the
      electoral roll, were sent a postal survey based on the UK Scleroderma Study Group
      questionnaire. Participants were classified as having RP if they had biphasic
      colour changes. RESULTS: There was a 67% response rate. The prevalence of RP was
      estimated to be 18.8% (95% Confidence Interval (CI) 13.0%-27.1%) in females and
      4.9% (95%CI 1.9%-13.0%) in males. The prevalence decreased with age. There was a
      higher prevalence in the warmer north of the country. People of Maori descent and
      in more manual occupations had more serve symptoms. Among those reporting
      symptoms 11% (95%CI 7%-17%) had consulted a doctor. CONCLUSION: New Zealand has
      high rates of RP. Few people with RP consult medical practitioners about their
      symptoms.

PMID- 20145688
TI  - The opinions of newly licensed drivers in New Zealand on the minimum car driver
      licensing age and reasons for getting a licence.
AB  - AIM: To investigate the opinions of newly licensed drivers towards the minimum
      age of car driver licensing, and reasons for getting a licence. METHOD: The New
      Zealand Drivers Study (NZDS) is a prospective cohort study of 3992 newly licensed
      car drivers in New Zealand, recruited between 1 February 2006 and 31 January 2008
      from driver licensing agencies and licensing courses throughout New Zealand. The
      cohort comprises 51% females and 49% males, 49% were aged 15 years and 28% 16-17
      years, 55% self-identified as New Zealand European, 21% Maori, 13% Pacific, 11%
      Asian, and 15% as "other". After passing the learner licence theory test all
      participants completed a questionnaire that included a range of questions on
      driver licensing topics, including minimum driver licence age and reasons for
      getting a car driver's licence. RESULTS: Overall, 51% of newly licensed drivers
      supported 15 years as the minimum age to start licensing but this varied
      significantly by the age, gender, and residential location of the learner driver.
      The most frequently reported reason for getting a licence related to independence
      and freedom. This applied equally to males and females, rural and urban drivers,
      and across all ages, although for learner drivers aged 18+ years, to drive to
      work was also a very important reason for having a licence. CONCLUSION: Contrary
      to what many may believe to be the case, the evidence presented here showed that
      there was not universal opposition by young people to raising the driver
      licensing age. Also those in rural and urban areas had much in common with
      respect to the reasons for obtaining a licence. With respect to the latter it is
      worth noting that travel for work was of most relevance to the learner drivers
      aged 18 years or older. Overall, these findings suggest that increasing the
      minimum age for licensing would have relatively little impact on essential travel
      among young people in New Zealand.

PMID- 20145689
TI  - "Pigs might fly"--a case of Erysipelothrix endocarditis.

PMID- 20145690
TI  - Get a handle on HaNDL (headache, neurological deficit, and lymphocytosis).
AB  - In the aftermath of an adverse event, an apology can bring comfort to the
      patient, forgiveness to the health practitioner, and help restore trust to their
      relationship. According to the Health and Disability Commissioner: "The way a
      practitioner handles the situation at the outset can influence a patient's
      decision about what further action to take, and an appropriate apology may
      prevent the problem escalating into a complaint to HDC". Yet, for many health
      practitioners saying "I'm sorry" remains a difficult and uncomfortable thing to
      do. We can help to bring down this wall of silence by developing a clear
      understanding of the importance of apologies to patients and health
      practitioners; appreciating the difference between expressing empathy and
      accepting legal responsibility for an adverse outcome; knowing the key elements
      of a full apology and when they should be used; and supporting those who have the
      honesty and courage to say "I'm sorry" to patients who have been harmed while
      receiving healthcare.

PMID- 20145691
TI  - Medical image. Calcified facial haematoma.
AB  - Doctors have been promoting alcohol as a health tonic for a very long time. The
      last 30 years has seen the accumulation of a considerable medical literature
      investigating the potential role of alcohol use as a protection against coronary
      heart disease. When viewed through the lens of two major early reviews in the mid
      1980s, Sir Richard Doll's contributions of the mid-1990s, two large meta-analyses
      of 10 years ago and two most recent overviews, the health-giving properties of
      alcohol use become increasingly debatable. The influence of the alcohol industry
      is raised as a factor in the exaggeration of alcohol use as a health
      intervention, in similar fashion to activities of pharmaceutical companies. The
      status of alcohol as a potentially dangerous recreational drug is emphasised as a
      warning against talking up alcohol as a cardio-protection manoeuvre by anyone.

PMID- 20145692
TI  - Medical student selection in New Zealand: looking to the future.
AB  - AIMS: To review whether current New Zealand (NZ) medical student selection
      policies are likely to result in specialists prepared to work in areas of
      greatest health need in the future. METHOD: This paper describes approaches used
      to select medical students, with some details about NZ medical student cohorts.
      It then discusses the evidence linking selection and career choice. RESULTS AND
      CONCLUSIONS: Selection processes have to serve multiple purposes and no tools are
      ideal. The NZ medical student population is more diverse than previously with
      more females than males, and higher proportions of students who are Maori,
      Pacific, rural, Asian or born overseas. Tracking projects are already underway to
      obtain data to better understand the effect of student factors on career choice.
      The Maori and Pacific Admission Scheme and Rural Origin Medical Preferential
      Entry affirmative action pathways have been successful, but to increase the
      number of doctors who identify as Maori or Pacific will require a larger pool of
      students with strong educational backgrounds from which to select. The strongest
      evidence between selection and future practice exists for students from rural
      backgrounds - they are more likely to practice in rural areas and to enter
      general practice. Therefore, increasing the numbers or rural students, or
      broadening the definition of 'rural', should be considered.

PMID- 20145693
TI  - Obesity and mental disorders in the Maori population of New Zealand: the
      difficulties conducting culturally specific research.

PMID- 20145694
TI  - Smoker misperceptions around tobacco: national survey data of particular
      relevance to protecting Maori health.

PMID- 20145695
TI  - Open access: science and undeveloped countries, a reality of discrimination.

PMID- 20145696
TI  - Heterophile antibodies and troponin results: implications in rural setting.

PMID- 20145697
TI  - Changes to health service delivery--successes and pitfalls.

PMID- 20145698
TI  - Auckland community laboratory contract: the most monumental disaster in health
      management in the past 60 years?

PMID- 20145699
TI  - Silicon electronics on silk as a path to bioresorbable, implantable devices.
AB  - Many existing and envisioned classes of implantable biomedical devices require
      high performance electronicssensors. An approach that avoids some of the longer
      term challenges in biocompatibility involves a construction in which some parts
      or all of the system resorbs in the body over time. This paper describes
      strategies for integrating single crystalline silicon electronics, where the
      silicon is in the form of nanomembranes, onto water soluble and biocompatible
      silk substrates. Electrical, bending, water dissolution, and animal toxicity
      studies suggest that this approach might provide many opportunities for future
      biomedical devices and clinical applications.

PMID- 20145700
TI  - Contributions of domain wall motion to complex electromechanical coefficients of
      0.62Pb(Mg(13)Nb(23))O(3)-0.38PbTiO(3) crystals.
AB  - The loss behavior of 0.62Pb(Mg(13)Nb(23))O(3)-0.38PbTiO(3) (PMN-38%PT)
      ferroelectric single crystal poled along [001](c) was investigated. It was found
      that the complex electromechanical coefficients and loss factors change
      dramatically at the coercive field E(c) around 250 Vmm, representing the
      intrinsic switching barrier. Since the energy loss is related to the domain wall
      motion, the imaginary parts of the electromechanical coefficients can be used to
      study the degree of domain wall motions in relaxor-based ferroelectric single
      crystals. Experimental results indicate that for this system, domain wall motion
      contributes significantly to the imaginary parts of electromechanical
      coefficients. In addition, [001](c) poled PMN-38%PT single crystals have much
      larger mechanical loss factor compared to that of conventional single crystal
      like LiNbO(3). This phenomenon is proved to be closely related to 90 degrees
      domain wall motion in this crystal system.

PMID- 20145701
TI  - BALB/c mice vaccinated with Leishmania major ribosomal proteins extracts combined
      with CpG oligodeoxynucleotides become resistant to disease caused by a secondary
      parasite challenge.
AB  - Leishmaniasis is an increasing public health problem and effective vaccines are
      not currently available. We have previously demonstrated that vaccination with
      ribosomal proteins extracts administered in combination of CpG
      oligodeoxynucleotides protects susceptible BALB/c mice against primary Leishmania
      major infection. Here, we evaluate the long-term immunity to secondary infection
      conferred by this vaccine. We show that vaccinated and infected BALB/c mice were
      able to control a secondary Leishmania major challenge, since no inflammation and
      very low number of parasites were observed in the site of reinfection. In
      addition, although an increment in the parasite burden was observed in the
      draining lymph nodes of the primary site of infection we did not detected
      inflammatory lesions at that site. Resistance against reinfection correlated to a
      predominant Th1 response against parasite antigens. Thus, cell cultures
      established from spleens and the draining lymph node of the secondary site of
      infection produced high levels of parasite specific IFN-gamma in the absence of
      IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high
      IgG2a/IgG1 ratio for anti-Leishmania antibodies. Our results suggest that
      ribosomal vaccine, which prevents pathology in a primary challenge, in
      combination with parasite persistence might be effective for long-term
      maintenance of immunity.

PMID- 20145702
TI  - Low-frequency low-intensity ultrasounds do not influence the survival and immune
      functions of cultured keratinocytes and dendritic cells.
AB  - Low-frequency ultrasounds (US) are used to enhance drug transdermal transport.
      Although this phenomenon has been extensively analyzed, information on US effects
      on the single skin cell components is limited. Here, we investigated the possible
      effects of low-frequency US on viability and immune functions of cultured human
      keratinocytes and dendritic cells (DC), skin cells involved in the regulation of
      many immune-mediated dermatoses. We demonstrated that US, employed at low
      frequency (42 KHz) and low-intensity (0.15 W/cm(2)) values known to enhance drug
      and water transdermal transport, did not affect extracellular-signal-regulated
      kinase (ERK)1/2 activation, cell viability, or expression of adhesion molecules
      in cultured keratinocytes. Moreover, US at these work frequency and intensity did
      not influence the keratinocyte expression and release of immunomodulatory
      molecules. Similarly, cultured DC treated with low-frequency low-intensity US
      were viable, and did not show an altered membrane phenotype, cytokine profile,
      nor antigen presentation ability. However, intensity enhancement of low-frequency
      US to 5 W/cm(2) determined an increase of the apoptotic rate of both
      keratinocytes and DC as well as keratinocyte CXCL8 release and ERK1/2 activation,
      and DC CD40 expression. Our study sustains the employment of low-frequency and
      low-intensity US for treatment of those immune skin disorders, where
      keratinocytes and DC have a pathogenetic role.

PMID- 20145703
TI  - The role of lipopeptidophosphoglycan in the immune response to Entamoeba
      histolytica.
AB  - The sensing of Pathogen Associated Molecular Patterns (PAMPs) by innate immune
      receptors, such as Toll-like receptors (TLRs), is the first step in the
      inflammatory response to pathogens. Entamoeba histolytica, the etiological agent
      of amebiasis, has a surface molecule with the characteristics of a PAMP. This
      molecule, which was termed lipopeptidophosphoglycan (LPPG), is recognized through
      TLR2 and TLR4 and leads to the release of cytokines from human monocytes,
      macrophages, and dendritic cells; LPPG-activated dendritic cells have increased
      expression of costimulatory molecules. LPPG activates NKT cells in a CD1d
      dependent manner, and this interaction limits amebic liver abscess development.
      LPPG also induces antibody production, and anti-LPPG antibodies prevent disease
      development in animal models of amebiasis. Because LPPG is recognized by both the
      innate and the adaptive immune system (it is a "Pamptigen"), it may be a good
      candidate to develop a vaccine against E. histolytica infection and an effective
      adjuvant.

PMID- 20145704
TI  - Molecular characterization of the ghrelin and ghrelin receptor genes and effects
      on fat deposition in chicken and duck.
AB  - Ghrelin (GHRL) and its receptor (GHSR) are involved in various bioactivities. In
      this study, the complete cDNA and 5' flanking region of the duck GHRL (dGHRL)
      gene and a 3717 bp fragment of the duck GHSR (dGHSR) gene were obtained. A total
      of 19, 8, 43, and 48 SNPs identified in 2751, 1358, 3671, and 3567 bp of the
      chicken GHRL (cGHRL), chicken GHSR (cGHSR), dGHRL, and dGHSR genes, respectively.
      Both cGHRL and dGHRL were expressed predominantly in the proventriculus, whereas
      the highest mRNA levels of cGHSR and dGHSR were detected in the breast muscle and
      pituitary. Association analysis showed that C-2047G, A-2355C, and A-2220C of the
      cGHRL gene were significantly associated with abdominal fat weight (AFW; P =
      .01), crude protein content of leg muscle (CPCLM; P = .02), and CPCLM (P =
      .0009), respectively. C-1459T of the cGHSR gene was also significantly associated
      with CPCLM (P = .0004). C-729T of dGHRL and A3427T of dGHSR were both
      significantly associated with subcutaneous fat thickness (SFT; P = .04). It was
      indicated by this study that the GHRL and GHSR genes were related to fat
      deposition in both chicken and duck.

PMID- 20145705
TI  - Similarity and diversity in macrophage activation by nematodes, trematodes, and
      cestodes.
AB  - This review summarizes current knowledge of macrophages in helminth infections,
      with a focus not only on delineating the striking similarities in macrophage
      phenotype between diverse infections but also on highlighting the differences.
      Findings from many different labs illustrate that macrophages in helminth
      infection can act as anti-parasite effectors but can also act as powerful immune
      suppressors. The specific role for their alternative (Th2-mediated) activation in
      helminth killing or expulsion versus immune regulation remains to be determined.
      Meanwhile, the rapid growth in knowledge of alternatively activated macrophages
      will require an even more expansive view of their potential functions to include
      repair of host tissue and regulation of host metabolism.

PMID- 20145706
TI  - VHL frameshift mutation as target of nonsense-mediated mRNA decay in Drosophila
      melanogaster and human HEK293 cell line.
AB  - There are many well-studied examples of human phenotypes resulting from nonsense
      or frameshift mutations that are modulated by Nonsense-Mediated mRNA Decay (NMD),
      a process that typically degrades transcripts containing premature termination
      codons (PTCs) in order to prevent translation of unnecessary or aberrant
      transcripts. Different types of germline mutations in the VHL gene cause the von
      Hippel-Lindau disease, a dominantly inherited familial cancer syndrome with a
      marked phenotypic variability and age-dependent penetrance. By generating the
      Drosophila UAS:Upf1(D45B) line we showed the possible involvement of NMD
      mechanism in the modulation of the c.172delG frameshift mutation located in the
      exon 1 of Vhl gene. Further, by Quantitative Real-time PCR (QPCR) we demonstrated
      that the corresponding c.163delG human mutation is targeted by NMD in human HEK
      293 cells. The UAS:Upf1(D45B) line represents a useful system to identify novel
      substrates of NMD pathway in Drosophila melanogaster. Finally, we suggest the
      possible role of NMD on the regulation of VHL mutations.

PMID- 20145707
TI  - Characterization of major surface protease homologues of Trypanosoma congolense.
AB  - Trypanosomes encode a family of proteins known as Major Surface Metalloproteases
      (MSPs). We have identified six putative MSPs encoded within the partially
      sequenced T. congolense genome. Phylogenic analysis indicates that T. congolense
      MSPs belong to five subfamilies that are conserved among African trypanosome
      species. Molecular modeling, based on the known structure of Leishmania Major
      GP63, reveals subfamily-specific structural variations around the putative active
      site despite conservation of overall structure, suggesting that each MSP
      subfamily has evolved to recognize distinct substrates. We have cloned and
      purified a protein encoding the amino-terminal domain of the T. congolense
      homologue TcoMSP-D (most closely related to Leishmania GP63). We detect TcoMSP-D
      in the serum of T. congolense-infected mice. Mice immunized with the amino
      terminal domain of TcoMSP-D generate a persisting IgG1 antibody response.
      Surprisingly, a low-dose challenge of immunized mice with T. congolense
      significantly increases susceptibility to infection, indicating that immunity to
      TcoMSP-D is a factor affecting virulence.

PMID- 20145708
TI  - Identification of the Leishmania major proteins LmjF07.0430, LmjF07.0440, and
      LmjF27.2440 as components of fatty acid synthase II.
AB  - Leishmania major causes leishmaniasis and is grouped within the Trypanosomatidae
      family, which also includes the etiologic agent for African sleeping sickness,
      Trypanosoma brucei. Previous studies on T. brucei showed that acyl carrier
      protein (ACP) of mitochondrial fatty acid synthase type 2 (FASII) plays a crucial
      role in parasite survival. Additionally, 3-oxoacyl-ACP synthase TbKASIII as well
      as TbHTD2 representing 3-hydroxyacyl-ACP dehydratase were also identified;
      however, 3-oxoacyl-ACP reductase TbKAR1 has hitherto evaded positive
      identification. Here, potential Leishmania FASII components LmjF07.0440 and
      LmjF07.0430 were revealed as 3-hydroxyacyl-ACP dehydratases LmHTD2-1 and LmHTD2
      2, respectively, whereas LmjF27.2440 was identified as LmKAR1. These Leishmania
      proteins were ectopically expressed in Saccharomyces cerevisiae htd2Delta or
      oar1Delta respiratory deficient cells lacking the corresponding mitochondrial
      FASII enzymes Htd2p and Oar1p. Yeast mutants producing mitochondrially targeted
      versions of the parasite proteins resembled the self-complemented cells for
      respiratory growth. This is the first identification of a FASII-like 3-oxoacyl
      ACP reductase from a kinetoplastid parasite.

PMID- 20145709
TI  - Are the immunocompetence and the presence of metazoan parasites in cyprinid fish
      affected by reproductive efforts of cyprinid fish?
AB  - Each organism has the limited resources of energy that is distributed among
      important life traits. A trade-off between immune response and other
      physiological demands of organism especially costly reproduction is expected.
      Leuciscus cephalus, the cyprinid fish, was investigated during three periods
      varying in reproductive investment, that is, before-breeding, breeding, and after
      breeding periods. We tested whether a potentially limited investment in immunity
      during the breeding is associated with higher susceptibility to the metazoan
      parasites. Following the immunocompetence handicap and sperm protection
      hypotheses, males expressing more elaborated sexual ornamentation should produce
      better quality sperm and be more parasitized. We found that reproductive
      investments in fish play an important role for energy allocation into somatic
      condition, immunity, and reproduction. The immune parameters including
      respiratory burst and leukocyte count were higher in breeding; however, parasite
      species richness and abundance appeared low. Males investing more in spawning
      tubercles reached high spermatocrite and were more parasitized by digeneans.

PMID- 20145710
TI  - A new MAP kinase protein involved in estradiol-stimulated reproduction of the
      helminth parasite Taenia crassiceps.
AB  - MAP kinases (MAPK) are involved in the regulation of cellular processes such as
      reproduction and growth. In parasites, the role of MAPK has been scarcely
      studied. Here, we describe the participation of an ERK-like protein in estrogen
      dependent reproduction of the helminth parasite Taenia crassiceps. Our results
      show that 17beta-estradiol induces a concentration-dependent increase in the bud
      number of in vitro cultured cysticerci. If parasites are also incubated in
      presence of an ERK-inhibitor, the stimulatory effect of estrogen is blocked. The
      expression of ERK-like mRNA and its corresponding protein was detected in the
      parasite. The ERK-like protein was over-expressed by all treatments.
      Nevertheless, a strong induction of phosphorylation of this protein was observed
      only in response to 17beta-estradiol. Cross-contamination by host cells was
      discarded by flow cytometry analysis. Parasite cells expressing the ERK-like
      protein were exclusively located at the subtegument tissue by confocal
      microscopy. Finally, the ERK-like protein was separated by bidimensional
      electrophoresis and then sequenced, showing the conserved TEY activation motif,
      typical of all known ERK 1/2 proteins. Our results show that an ERK-like protein
      is involved in the molecular signalling during the interaction between the host
      and T. crassiceps, and may be considered as target for anti-helminth drugs
      design.

PMID- 20145711
TI  - An experimental approach for the identification of conserved secreted proteins in
      trypanosomatids.
AB  - Extracellular factors produced by Leishmania spp., Trypanosoma cruzi, and
      Trypanosoma brucei are important in the host-parasite relationship. Here, we
      describe a genome-based approach to identify putative extracellular proteins
      conserved among trypanosomatids that are likely involved in the classical
      secretory pathway. Potentially secreted proteins were identified by bioinformatic
      analysis of the T. cruzi genome. A subset of thirteen genes encoding unknown
      proteins with orthologs containing a signal peptide sequence in L. infantum, L.
      major, and T. brucei were transfected into L. infantum. Tagged proteins detected
      in the extracellular medium confirmed computer predictions in about 25% of the
      hits. Secretion was confirmed for two L. infantum orthologs proteins using the
      same experimental system. Infectivity studies of transgenic Leishmania parasites
      suggest that one of the secreted proteins increases parasite replication inside
      macrophages. This methodology can identify conserved secreted proteins involved
      in the classical secretory pathway, and they may represent potential virulence
      factors in trypanosomatids.

PMID- 20145713
TI  - Low-dose dexamethasone therapy from infancy of virilizing congenital adrenal
      hyperplasia.
AB  - Objective. To assess the growth and control of adrenal androgen secretion in
      children with virilizing congenital adrenal hyperplasia (CAH) treated with
      dexamethasone. Method. We examined doses used, control of adrenal androgen
      secretion, and growth and skeletal maturation of 8 children with CAH treated with
      dexamethasone beginning in infancy. Results. 3 boys and 5 girls with classical
      CAH (17-hydroxyprogesterone at diagnosis >20,000 ng/dL) were treated with
      dexamethasone beginning at diagnosis (<10 days of age). Patients were also
      treated with fludrocortisone and sodium chloride. The average initial medication
      dose was 0.1 mg (0.28 +/- 0.015 mg/m(2)); all doses were given in the morning
      using a dosing syringe to administer a 0.1 mg/mL elixir. The children were
      treated for 6.5 +/- 2.0 years over which time the change in bone age to
      chronological age ratio (DeltaBA/DeltaCA) was 0.9 +/- 0.06. Most recent height Z'
      scores were +0.5 +/- 0.2, and body mass index (BMI) scores were 18 +/- 0.2. Late
      afternoon levels of 17-hydroxyprogesterone, androstenedione, and testosterone
      were 780 +/- 238 ng/dL (23.4 +/- 7 nmol/L), 42 +/- 10 ng/dL (1.4 +/- 0.3 nmol/L),
      and 11.5 +/- 3 ng/dL; (0.4 +/- 0.1 nmol/L), respectively. Conclusions. These
      observations show that low doses of dexamethasone can be used to effectively
      treat CAH beginning in infancy.

PMID- 20145712
TI  - The receptor for advanced glycation end products (RAGE) and the lung.
AB  - The receptor for advanced glycation end products (RAGE) is a member of the
      immunoglobulin superfamily of cell surface molecules. As a pattern-recognition
      receptor capable of binding a diverse range of ligands, it is typically expressed
      at low levels under normal physiological conditions in the majority of tissues.
      In contrast, the lung exhibits high basal level expression of RAGE localised
      primarily in alveolar type I (ATI) cells, suggesting a potentially important role
      for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE
      levels has been implicated in the pathogenesis of a variety of pulmonary
      disorders including cancer and fibrosis. Furthermore, its soluble isoforms,
      sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI
      cell injury. Whilst RAGE undoubtedly plays an important role in the biology of
      the lung, it remains unclear as to the exact nature of this contribution under
      both physiological and pathological conditions.

PMID- 20145714
TI  - Ret Finger Protein: An E3 Ubiquitin Ligase Juxtaposed to the XY Body in Meiosis.
AB  - During prophase I of male meiosis, the sex chromosomes form a compact structure
      called XY body that associates with the nuclear membrane of pachytene
      spermatocytes. Ret Finger Protein is a transcriptional repressor, able to
      interact with both nuclear matrix-associated proteins and double-stranded DNA. We
      report the precise and unique localization of Ret Finger Protein in pachytene
      spermatocytes, in which Ret Finger Protein takes place of lamin B1, between the
      XY body and the inner nuclear membrane. This localization of Ret Finger Protein
      does not seem to be associated with O-glycosylation or sumoylation. In addition,
      we demonstrate that Ret Finger Protein contains an E3 ubiquitin ligase activity.
      These observations lead to an attractive hypothesis in which Ret Finger Protein
      would be involved in the positioning and the attachment of XY body to the nuclear
      lamina of pachytene spermatocytes.

PMID- 20145715
TI  - Comparative Analyses of Transcriptional Profiles in Mouse Organs Using a
      Pneumonic Plague Model after Infection with Wild-Type Yersinia pestis CO92 and
      Its Braun Lipoprotein Mutant.
AB  - We employed Murine GeneChips to delineate the global transcriptional profiles of
      the livers, lungs, and spleens in a mouse pneumonic plague infection model with
      wild-type (WT) Y. pestis CO92 and its Braun lipoprotein (Deltalpp) mutant with
      reduced virulence. These organs showed differential transcriptional responses to
      infection with WT Y. pestis, but the overall host functional processes affected
      were similar across all three tissues. Gene expression alterations were found in
      inflammation, cytokine signaling, and apoptotic cell death-associated genes.
      Comparison of WT and Deltalpp mutant-infected mice indicated significant overlap
      in lipopolysaccharide- (LPS-) associated gene expression, but the absence of Lpp
      perturbed host cell signaling at critical regulatory junctions resulting in
      altered immune response and possibly host cell apoptosis. We generated a putative
      signaling pathway including major inflammatory components that could account for
      the synergistic action of LPS and Lpp and provided the mechanistic basis of
      attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of
      pneumonic plague.

PMID- 20145716
TI  - Human papillomavirus type distribution and correlation with cyto-histological
      patterns in women from the South of Italy.
AB  - Human papillomavirus (HPV) type-specific distribution was evaluated in genital
      samples collected from 654 women from the South of Italy undergoing voluntary
      screening and correlated with cyto-histological abnormalities. HPV DNA was
      detected in 45.9% of the samples, 41.7% of which had multiple infection and 89.0%
      had high-risk HPV infection. The prevalence of HPV infection and the rate of
      multiple infections decreased with age, suggesting natural selection of HPV types
      with better fitness. In line with other Italian studies, the most common HPV
      types were HPV-6 and HPV-16, followed by HPV-51, HPV-31, HPV-53, and HPV-66, in
      women with both normal and abnormal cytology. Cervical intraepithelial lesions
      grade 2 or 3 were associated with high-risk HPV-16, HPV-18, HPV-31, and HPV-51
      infection. These data indicate that prophylactic HPV vaccination is expected to
      reduce the burden of HPV-related cervical lesions in this population, but also
      suggest the potential utility of new vaccines with larger type coverage.

PMID- 20145717
TI  - Cross-correlation of motor activity signals from dc-magnetoencephalography, near
      infrared spectroscopy, and electromyography.
AB  - Neuronal and vascular responses due to finger movements were synchronously
      measured using dc-magnetoencephalography (dcMEG) and time-resolved near-infrared
      spectroscopy (trNIRS). The finger movements were monitored with electromyography
      (EMG). Cortical responses related to the finger movement sequence were extracted
      by independent component analysis from both the dcMEG and the trNIRS data. The
      temporal relations between EMG rate, dcMEG, and trNIRS responses were assessed
      pairwise using the cross-correlation function (CCF), which does not require epoch
      averaging. A positive lag on a scale of seconds was found for the maximum of the
      CCF between dcMEG and trNIRS. A zero lag is observed for the CCF between dcMEG
      and EMG. Additionally this CCF exhibits oscillations at the frequency of
      individual finger movements. These findings show that the dcMEG with a bandwidth
      up to 8 Hz records both slow and faster neuronal responses, whereas the vascular
      response is confirmed to change on a scale of seconds.

PMID- 20145718
TI  - Sleep, Hormones, and Circadian Rhythms throughout the Menstrual Cycle in Healthy
      Women and Women with Premenstrual Dysphoric Disorder.
AB  - A relationship exists between the sleep-wake cycle and hormone secretion, which,
      in women, is further modulated by the menstrual cycle. This interaction can
      influence sleep across the menstrual cycle in healthy women and in women with
      premenstrual dysphoric disorder (PMDD), who experience specific alterations of
      circadian rhythms during their symptomatic luteal phase along with sleep
      disturbances during this time. This review will address the variation of sleep at
      different menstrual phases in healthy and PMDD women, as well as changes in
      circadian rhythms, with an emphasis on their relationship with female sex
      hormones. It will conclude with a brief discussion on nonpharmacological
      treatments of PMDD which use chronotherapeutic methods to realign circadian
      rhythms as a means of improving sleep and mood in these women.

PMID- 20145719
TI  - Tree-Based Methods for Discovery of Association between Flow Cytometry Data and
      Clinical Endpoints.
AB  - We demonstrate the application and comparative interpretations of three tree
      based algorithms for the analysis of data arising from flow cytometry:
      classification and regression trees (CARTs), random forests (RFs), and logic
      regression (LR). Specifically, we consider the question of what best predicts CD4
      T-cell recovery in HIV-1 infected persons starting antiretroviral therapy with
      CD4 count between 200 and 350 cell/muL. A comparison to a more standard
      contingency table analysis is provided. While contingency table analysis and RFs
      provide information on the importance of each potential predictor variable, CART
      and LR offer additional insight into the combinations of variables that together
      are predictive of the outcome. In all cases considered, baseline CD3-DR
      CD56+CD16+ emerges as an important predictor variable, while the tree-based
      approaches identify additional variables as potentially informative. Application
      of tree-based methods to our data suggests that a combination of baseline immune
      activation states, with emphasis on CD8 T-cell activation, may be a better
      predictor than any single T-cell/innate cell subset analyzed. Taken together, we
      show that tree-based methods can be successfully applied to flow cytometry data
      to better inform and discover associations that may not emerge in the context of
      a univariate analysis.

PMID- 20145720
TI  - Autoantibodies to tumor-associated antigens in epithelial ovarian carcinoma.
AB  - This review will focus on recent knowledge related to circulating autoantibodies
      (AAbs) to tumor-associated antigens (TAAs) in epithelial ovarian carcinoma. So
      far, the following TAAs have been identified to elicit circulating AAbs in
      epithelial ovarian carcinoma: p53, homeobox proteins (HOXA7, HOXB7), heat shock
      proteins (HSP-27, HSP-90), cathepsin D, cancer-testis antigens (NY-ESO-1/LAGE-1),
      MUC1, GIPC-1, IL-8, Ep-CAM, and S100A7. Since AAbs to TAAs have been identified
      in the circulation of patients with early-stage cancer, it has been speculated
      that the assessment of a panel of AAbs specific for epithelial ovarian carcinoma
      TAAs might hold great potential as a novel tool for early diagnosis of epithelial
      ovarian carcinoma.

PMID- 20145721
TI  - Low-noise dynamic reconstruction for x-ray tomographic perfusion studies using
      low sampling rates.
AB  - Functional imaging based on tomographic X-ray imaging relies on the
      reconstruction of a temporal sequence of images which accurately reproduces the
      time attenuation curves of the tissue. The main constraints of these techniques
      are temporal resolution and dose. Using current techniques the data acquisition
      has to be performed fast so that the dynamic attenuation values can be regarded
      as static during the scan. Due to the relatively high number of repeated scans
      the dose per single scan has to be low yielding a poor signal-to-noise ratio
      (SNR) in the reconstructed images. In a previous publication a temporal
      interpolation scheme in the projection data space was relaxing the temporal
      resolution constraint. The aim of this contribution is the improvement of the
      SNR. A temporal smoothing term is introduced in the temporal interpolation scheme
      such that only the physiologic relevant bandwidth is considered. A significant
      increase of the SNR is achieved. The obtained level of noise only depends on the
      total dose applied and is independent of the number of scans and the SNR of a
      single reconstructed image. The approach might be the first step towards using
      slowly rotating CT systems for perfusion imaging like C-arm or small animal CT
      scanners.

PMID- 20145722
TI  - A seizure attributed to ofloxacine in a woman undergoing detoxification for
      alcohol dependence.
AB  - Objective. To report one case of seizure following administration of ofloxacin.
      Case Summary. A 38-year-old woman with alcohol dependence but no prior history of
      seizure disorder admitted in our inpatient alcohol detoxification program was
      prescribed ofloxacin four days after admission for a lower urinary tract
      infection. She was currently prescribed diazepam 30 mg per day. This treatment
      was continued without modification following admission. Forty eight hours after
      starting ofloxacin and after receiving five doses of oral ofloxacin, the patient
      experienced a seizure. Ofloxacin treatment was stopped and no further seizures
      occurred. Neurological examination of the patient, laboratory tests, computerized
      tomography with contrast enhancement and electroencephalography did not detect
      any abnormalities. Up to the last consultation, six months after admission, the
      patient has reported no recurrence of the seizure. Discussion. Quinolone
      antibiotics vary in their ability to induce seizures, with ofloxacin having one
      of the least potentials. In the present case, the seizure could be attributed in
      all probability to taking ofloxacin; since she had no previous history of
      seizures, she did not present an alcohol withdrawal syndrome, benzodiazepine
      treatment was not modified, the seizure occurred 48 h after taking ofloxacin, but
      seven days after stopping drinking, no alternative aetiologies for the seizure
      could be identified and no seizure recurrence was reported over the following
      seven months. Of reported cases of seizures in patients treated with
      fluoroquinolones, none concerned patients with alcohol dependence or patients
      treated with benzodiazepines. Conclusions. The present case alerts us to the
      possibility that seizures may occur in alcohol dependent patients treated with
      benzodiazepines who concomitantly prescribed a fluoroquinolone. These widely-used
      antibiotics should thus be prescribed with caution to patients undergoing
      detoxification for alcohol dependence, particularly if they are also taking
      benzodiazepines, irrespective of whether they have a previous history of seizures
      or not.

PMID- 20145723
TI  - FSH Injections and Ultrasonography Determine Presence of Ovarian Components in
      the Evaluation of Ovotesticular Disorders of Sex Development.
AB  - Three infants with ambiguous genitalia and suspected ovotestes were given
      recombinant FSH to induce ovarian follicular development. The development of
      follicles in the gonadal tissue suggested the presence of ovarian tissue in two
      of the three infants. This method may provide a means to better characterize
      gonadal anatomy in patients affected by disorders of sex development (DSD).
      Sonographic information poststimulation provided parents with earlier and more
      specific education and support concerning the possible need for confirmative
      gonadal biopsy treatment options.

PMID- 20145724
TI  - Ex utero intrapartum treatment for fetal oropharyngeal cyst.
AB  - Background. A prenatally diagnosed fetal anomaly that could compromise the fetal
      airway at delivery can be managed safely with the ex utero intrapartum treatment
      (EXIT) procedure. Case. A 26-year-old healthy primigravida was diagnosed during
      her midtrimester anatomic ultrasound survey with a fetal oropharyngeal cystic
      structure located at the base of the tongue. The neonatal airway was successfully
      secured intrapartum using the EXIT procedure. Conclusion. Maintenance of
      fetoplacental circulation until the fetal airway is secured has been described
      for a multitude of fetal anomalies including cystic hygroma and teratoma. The
      literature also recounts its use for the reversal of tracheal plugging for
      congenital diaphragmatic hernia. A multidisciplinary approach to the antenatal
      and intrapartum care is essential for the successful management of these cases.

PMID- 20145725
TI  - Oxandrolone Improves Height Velocity and BMI in Patients with Cystic Fibrosis.
AB  - Objective. To evaluate the effectiveness of oxandrolone in improving the
      nutritional status and linear growth of pediatric patients with cystic fibrosis
      (CF). Methods. Medical records of patients with CF treated with oxandrolone were
      reviewed for height z score, height velocity (HV), BMI z score, weight velocity
      (WV), Tanner stage, pulmonary function, liver enzyme levels, and any reported
      adverse events. Data were compared before (pre-Ox) and after (Ox) oxandrolone
      using a paired t-test. Results. 5 subjects (ages 8.5-14.5 years) were treated
      with oxandrolone 2.5 mg daily for 8-38 months. After 8-12 months of treatment,
      there was a statistically significant improvement in HV (pre-Ox = 5.3 +/- 1.4
      cm/yr, Ox = 8.3 +/- 1.2 cm/yr, P < .01) and BMI z score (pre-Ox = -0.61 +/- 1.04,
      Ox = -0.30 +/- 0.86, P = .02). Both height z score (pre-Ox = -1.64 +/- 0.63, Ox =
      -1.30 +/- 0.49, P = .057) and WV (pre-Ox = 4.2 +/- 3.7 kg/yr, Ox = 6.8 +/- 1.0
      kg/yr, P = .072) showed beneficial trends that did not reach statistical
      significance. No adverse events were reported. Conclusions. In this brief
      clinical report, oxandrolone improved the HV and BMI z score in patients with CF.
      Larger studies are needed to determine if oxandrolone is an effective, safe, and
      affordable option to stimulate appetite, improve weight gain, and promote linear
      growth in patients with CF.

PMID- 20145726
TI  - PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and
      Histone Alterations via Caspase-8 and FADD in Leukemia Cells.
AB  - Histone deacetylase inhibitors (HDACi) have become a promising new avenue for
      cancer therapy, and many are currently in Phase I/II clinical trials for various
      tumor types. In the present study, we show that apoptosis induction and histone
      alterations by PCI-24781, a novel hydroxamic acid-based HDAC inhibitor, require
      caspase-8 and the adaptor molecule, Fas-associated death domain (FADD), in acute
      leukemia cells. PCI-24781 treatment also causes an increase in superoxide levels,
      which has been reported for other HDACi. However, an antioxidant does not reverse
      histone alterations caused by PCI-24781, indicating that ROS generation is likely
      downstream of the effects that PCI-24781 exerts on histone H3. Taken together,
      these results provide insight into the mechanism of apoptosis induction by PCI
      24781 in leukemia by highlighting the roles of caspase-8, FADD and increased
      superoxide levels.

PMID- 20145728
TI  - The trend in mental health-related mortality rates in Australia 1916-2004:
      implications for policy.
AB  - BACKGROUND: This study determines the trend in mental health-related mortality
      (defined here as the aggregation of suicide and deaths coded as
      "mental/behavioural disorders"), and its relative numerical importance, and to
      argue that this has importance to policy-makers. Its results will have policy
      relevance because policy-makers have been predominantly concerned with cost
      containment, but a re-appraisal of this issue is occurring, and the trade-off
      between health expenditures and valuable gains in longevity is being emphasised
      now. This study examines longevity gains from mental health-related
      interventions, or their absence, at the population level. The study sums
      mortality data for suicide and mental/behavioural disorders across the relevant
      ICD codes through time in Australia for the period 1916-2004. There are two
      measures applied to the mortality rates: the conventional age-standardised
      headcount; and the age-standardised Potential Years of Life Lost (PYLL), a
      measure of premature mortality. Mortality rates formed from these data are
      analysed via comparisons with mortality rates for All Causes, and with
      circulatory diseases, cancer and motor vehicle accidents, measured by both
      methods. RESULTS: This study finds the temporal trend in mental health-related
      mortality rates (which reflects the longevity of people with mental illness) has
      worsened through time. There are no gains. This trend contrasts with the (known)
      gains in longevity from All Causes, and the gains from decreases achieved in
      previously rising mortality rates from circulatory diseases and motor vehicle
      accidents. Also, PYLL calculation shows mental health-related mortality is a
      proportionately greater cause of death compared with applying headcount metrics.
      CONCLUSIONS: There are several factors that could reverse this trend. First,
      improved access to interventions or therapies for mental disorders could decrease
      the mortality analysed here. Second, it is important also that new efficacious
      therapies for various mental disorders be developed. Furthermore, it is also
      important that suicide prevention strategies be implemented, particularly for at
      risk groups. To bring the mental health sector into parity with many other parts
      of the health system will require knowledge of the causative factors that
      underlie mental disorders, which can, in turn, lead to efficacious therapies. As
      in any case of a knowledge deficit, what is needed are resources to address that
      knowledge gap. Conceiving the problem in this way, ie as a knowledge gap,
      indicates the crucial role of research and development activity. This term
      implies a concern, not simply with basic research, but also with applied
      research. It is commonplace in other sectors of the economy to emphasise the
      trichotomy of invention, innovation and diffusion of new products and processes.
      This three-fold conception is also relevant to addressing the knowledge gap in
      the mental health sector.

PMID- 20145727
TI  - Linking ER Stress to Autophagy: Potential Implications for Cancer Therapy.
AB  - Different physiological and pathological conditions can perturb protein folding
      in the endoplasmic reticulum, leading to a condition known as ER stress. ER
      stress activates a complex intracellular signal transduction pathway, called
      unfolded protein response (UPR). The UPR is tailored essentially to reestablish
      ER homeostasis also through adaptive mechanisms involving the stimulation of
      autophagy. However, when persistent, ER stress can switch the cytoprotective
      functions of UPR and autophagy into cell death promoting mechanisms. Recently, a
      variety of anticancer therapies have been linked to the induction of ER stress in
      cancer cells, suggesting that strategies devised to stimulate its prodeath
      function or block its prosurvival function, could be envisaged to improve their
      tumoricidial action. A better understanding of the molecular mechanisms that
      determine the final outcome of UPR and autophagy activation by chemotherapeutic
      agents, will offer new opportunities to improve existing cancer therapies as well
      as unravel novel targets for cancer treatment.

PMID- 20145729
TI  - The inflammatory response seen when human omental adipose tissue explants are
      incubated in primary culture is not dependent upon albumin and is primarily in
      the nonfat cells.
AB  - BACKGROUND: The present studies were designed to investigate the changes in gene
      expression during in vitro incubation of human visceral omental adipose tissue
      explants as well as fat cells and nonfat cells derived from omental fat. METHODS:
      Adipose tissue was obtained from extremely obese women undergoing bariatric
      surgery. Explants of the tissue as well as fat cells and the nonfat cells derived
      by digestion with collagenase were incubated for 20 minutes to 48 h. The
      expression of interleukin 1beta [IL-1beta], tumor necrosis factor alpha
      [TNFalpha], interleukin 8 [IL-8], NFkappaB(1)p50 subunit, hypoxia-inducible
      factor 1alpha [HIF1alpha], omentin/intelectin, and 11beta-hydroxysteroid
      dehydrogenase 1 [11beta-HSD1] mRNA were measured by qPCR as well as the release
      of IL-8 and TNFalpha. RESULTS: There was an inflammatory response at 2 h in
      explants of omental adipose tissue that was reduced but not abolished in the
      absence of albumin from the incubation buffer for IL-8, IL-1beta and TNFalpha.
      There was also an inflammatory response with regard to upregulation of HIF1alpha
      and NFkappaB1 gene expression that was unaffected whether albumin was present or
      absent from the medium. In the nonfat cells derived by a 2 h collagenase
      digestion of omental fat there was an inflammatory response comparable but not
      greater than that seen in tissue. The exception was HIF1alpha where the marked
      increase in gene expression was primarily seen in intact tissue. The inflammatory
      response was not seen with respect to omentin/intelectin. Over a subsequent 48 h
      incubation there was a marked increase in IL-8 mRNA expression and IL-8 release
      in adipose tissue explants that was also seen to the same extent in the nonfat
      cells incubated in the absence of fat cells. CONCLUSION: The marked inflammatory
      response seen when human omental adipose tissue is incubated in vitro is reduced
      but not abolished in the presence of albumin with respect to IL-1beta, TNFalpha,
      IL-8, and is primarily in the nonfat cells of adipose tissue.

PMID- 20145731
TI  - The influence of exercise and BMI on injuries and illnesses in overweight and
      obese individuals: a randomized control trial.
AB  - BACKGROUND: Medically treated injuries have been shown to increase with
      increasing body mass index (BMI). Information is lacking on the frequency and
      type of injuries and illnesses among overweight and obese adults who engage in
      regular physical activities as part of weight loss or weight gain prevention
      programs. METHODS: Sedentary adults with BMIs between 25 and 40 kg/m(2 )(n = 397)
      enrolled in one of two randomized clinical trials that emphasized exercise as
      part of a weight loss or weight gain prevention program. Interventions differed
      by duration of the exercise goal (150, 200, or 300 minutes/week or control
      group). Walking was prescribed as the primary mode of exercise. At six month
      intervals, participants were asked, "During the past six months, did you have any
      injury or illness that affected your ability to exercise?" Longitudinal models
      were used to assess the effects of exercise and BMI on the pattern of
      injuries/illnesses attributed to exercise over time; censored linear regression
      was used to identify predictors of time to first injury/illness attributed to
      exercise. RESULTS: During the 18-month study, 46% reported at least one
      injury/illness, and 32% reported at least one injury that was attributed to
      exercise. Lower-body musculoskeletal injuries (21%) were the most commonly
      reported injury followed by cold/flu/respiratory infections (18%) and back
      pain/injury (10%). Knee injuries comprised one-third of the lower-body
      musculoskeletal injuries. Only 7% of the injuries were attributed to exercise
      alone, and 59% of the injuries did not involve exercise. BMI (p </= 0.01) but not
      exercise (p >/= 0.41) was significantly associated with time to first injury and
      injuries over time. Participants with higher BMIs were injured earlier or had
      increased odds of injury over time than participants with lower BMIs. Due to the
      linear dose-response relationship between BMI and injury/illness, any weight loss
      and reduction in BMI was associated with a decrease risk of injury/illness and
      delay in time to injury/illness. CONCLUSIONS: Overweight and obese adults who
      were prescribed exercise as part of weight loss or weight gain prevention
      intervention were not at increased risk of injury compared to overweight adults
      randomized not to participate in prescribed exercise. Since onset of
      injury/illness and pattern of injuries over time in overweight and obese
      individuals were attributed to BMI, weight reduction may be an avenue to reduce
      the risk of injury/illness in sedentary and previously sedentary overweight and
      obese adults. TRIAL REGISTRATION: Clinicaltrials.gov NCT00177502 and NCT00177476.

PMID- 20145730
TI  - Canine and feline vector-borne diseases in Italy: current situation and
      perspectives.
AB  - In Italy, dogs and cats are at risk of becoming infected by different vector
      borne pathogens, including protozoa, bacteria, and helminths. Ticks, fleas,
      phlebotomine sand flies, and mosquitoes are recognized vectors of pathogens
      affecting cats and dogs, some of which (e.g., Anaplasma phagocytophilum, Borrelia
      burgdorferi, Dipylidium caninum, Leishmania infantum, Dirofilaria immitis, and
      Dirofilaria repens) are of zoonotic concern. Recent studies have highlighted the
      potential of fleas as vectors of pathogens of zoonotic relevance (e.g.,
      Rickettsia felis) in this country. While some arthropod vectors (e.g., ticks and
      fleas) are present in certain Italian regions throughout the year, others (e.g.,
      phlebotomine sand flies) are most active during the summer season. Accordingly,
      control strategies, such as those relying on the systematic use of acaricides and
      insecticides, should be planned on the basis of the ecology of both vectors and
      pathogens in different geographical areas in order to improve their effectiveness
      in reducing the risk of infection by vector-borne pathogens. This article reviews
      the current situation and perspectives of canine and feline vector-borne diseases
      in Italy.

PMID- 20145732
TI  - Osteopathic Medicine and Primary Care: one journal, two audiences.
AB  - Osteopathic Medicine and Primary Care (OMPC) enters its fourth year of operation
      in 2010 under the umbrella of BioMed Central. Osteopathic Medicine and Primary
      Care strives to promote and advance research and scholarly work within the fields
      of osteopathic medicine and primary care. In so doing, OMPC welcomes submissions
      from clinicians within both the osteopathic and allopathic medical professions,
      and from other professionals having interests in primary care, including health
      care delivery, public health, and evidence-based medicine. Osteopathic Medicine
      and Primary Care offers fair and expeditious peer review (mean time from
      submission to publication, 118 days), retention of copyright for authors,
      unlimited online distribution and access without charge to readers, indexing in
      PubMed, and archiving in PubMed Central. In 2010, there will be an increased
      availability of waivers or discounts of article processing charges via several
      mechanisms for eligible authors who submit qualified manuscripts, especially in
      the field of primary care.

PMID- 20145733
TI  - Are acupoints specific for diseases? A systematic review of the randomized
      controlled trials with sham acupuncture controls.
AB  - BACKGROUND: The results of many clinical trials and experimental studies
      regarding acupoint specificity are contradictory. This review aims to investigate
      whether a difference in efficacy exists between ordinary acupuncture on specific
      acupoints and sham acupuncture controls on non-acupoints or on irrelevant
      acupoints. METHODS: Databases including Medline, Embase, AMED and Chinese
      Biomedical Database were searched to identify randomized controlled trials
      published between 1998 and 2009 that compared traditional body acupuncture on
      acupoints with sham acupuncture controls on irrelevant acupoints or non-acupoints
      with the same needling depth. The Cochrane Collaboration's tool for assessing
      risk of bias was employed to address the quality of the included trials. RESULTS:
      Twelve acupuncture clinical trials with sham acupuncture controls were identified
      and included in the review. The conditions treated varied. Half of the included
      trials had positive results on the primary outcomes and demonstrated acupoint
      specificity. However, among those six trials (total sample size: 985) with low
      risk of bias, five trials (sample size: 940) showed no statistically significant
      difference between proper and sham acupuncture treatments. CONCLUSION: This
      review did not demonstrate the existence of acupoint specificity. Further
      clinical trials with larger sample sizes, optimal acupuncture treatment protocols
      and appropriate sham acupuncture controls are required to resolve this important
      issue.

PMID- 20145734
TI  - A method to predict breast cancer stage using Medicare claims.
AB  - BACKGROUND: In epidemiologic studies, cancer stage is an important predictor of
      outcomes. However, cancer stage is typically unavailable in medical insurance
      claims datasets, thus limiting the usefulness of such data for epidemiologic
      studies. Therefore, we sought to develop an algorithm to predict cancer stage
      based on covariates available from claims-based data. METHODS: We identified a
      cohort of 77,306 women age >/= 66 years with stage I-IV breast cancer, using the
      Surveillence Epidemiology and End Results (SEER)-Medicare database. We formulated
      an algorithm to predict cancer stage using covariates (demographic, tumor, and
      treatment characteristics) obtained from claims. Logistic regression models
      derived prediction equations in a training set, and equations' test
      characteristics (sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value [NPV]) were calculated in a validation set. RESULTS: Of
      the entire sample of women diagnosed with invasive breast cancer, 51% had stage
      I; 26% stage II; 11% stage III; and 4% stage IV disease. The equation predicting
      stage IV disease achieved sensitivity of 81%, specificity 89%, positive
      predictive value (PPV) 24%, and negative predictive value (NPV) 99%, while the
      equation distinguishing stage I/II from stage III disease achieved sensitivity
      83%, specificity 78%, PPV 98%, and NPV 31%. Combined, the equations most
      accurately identified early stage disease and ascertained a sample in which 98%
      of patients were stage I or II. CONCLUSIONS: A claims-based algorithm was
      utilized to predict breast cancer stage, and was particularly successful when
      used to identify early stage disease. These prediction equations may be applied
      in future studies of breast cancer patients, substantially improving the utility
      of claims-based studies in this group. This method may similarly be employed to
      develop algorithms permitting claims-based epidemiologic studies of patients with
      other cancers.

PMID- 20145735
TI  - Mode of antiviral action of silver nanoparticles against HIV-1.
AB  - BACKGROUND: Silver nanoparticles have proven to exert antiviral activity against
      HIV-1 at non-cytotoxic concentrations, but the mechanism underlying their HIV
      inhibitory activity has not been not fully elucidated. In this study, silver
      nanoparticles are evaluated to elucidate their mode of antiviral action against
      HIV-1 using a panel of different in vitro assays. RESULTS: Our data suggest that
      silver nanoparticles exert anti-HIV activity at an early stage of viral
      replication, most likely as a virucidal agent or as an inhibitor of viral entry.
      Silver nanoparticles bind to gp120 in a manner that prevents CD4-dependent virion
      binding, fusion, and infectivity, acting as an effective virucidal agent against
      cell-free virus (laboratory strains, clinical isolates, T and M tropic strains,
      and resistant strains) and cell-associated virus. Besides, silver nanoparticles
      inhibit post-entry stages of the HIV-1 life cycle. CONCLUSIONS: These properties
      make them a broad-spectrum agent not prone to inducing resistance that could be
      used preventively against a wide variety of circulating HIV-1 strains.

PMID- 20145736
TI  - Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and
      PSEN1 A431E-associated familial Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is associated with deposition of amyloid
      beta (Abeta) in the brain, which is reflected by low concentration of the Abeta1
      42 peptide in the cerebrospinal fluid (CSF). There are at least 15 additional
      Abeta peptides in human CSF and their relative abundance pattern is thought to
      reflect the production and degradation of Abeta. Here, we test the hypothesis
      that AD is characterized by a specific CSF Abeta isoform pattern that is distinct
      when comparing sporadic AD (SAD) and familial AD (FAD) due to different
      mechanisms underlying brain amyloid pathology in the two disease groups. RESULTS:
      We measured Abeta isoform concentrations in CSF from 18 patients with SAD, 7
      carriers of the FAD-associated presenilin 1 (PSEN1) A431E mutation, 17 healthy
      controls and 6 patients with depression using immunoprecipitation-mass
      spectrometry. Low CSF levels of Abeta1-42 and high levels of Abeta1-16
      distinguished SAD patients and FAD mutation carriers from healthy controls and
      depressed patients. SAD and FAD were characterized by similar changes in Abeta1
      42 and Abeta1-16, but FAD mutation carriers exhibited very low levels of Abeta1
      37, Abeta1-38 and Abeta1-39. CONCLUSION: SAD patients and PSEN1 A431E mutation
      carriers are characterized by aberrant CSF Abeta isoform patterns that hold
      clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit
      low levels of Abeta1-37, Abeta1-38 and Abeta1-39; fragments that are normally
      produced by gamma-secretase, suggesting that the PSEN1 A431E mutation modulates
      gamma-secretase cleavage site preference in a disease-promoting manner.

PMID- 20145737
TI  - Plantar Fasciitis: What's an Evidence-Informed Consumer to Do?

PMID- 20145738
TI  - Predictors of gait speed in patients after hip fracture.
AB  - PURPOSE: Following hip fracture, patients demonstrate greatly reduced walking
      speeds 1 year later compared with age-matched elders. The purpose of our study
      was to examine the factors that relate to gait speed in patients after hip
      fracture. METHODS: Forty-two men and women (mean age 79 +/- 7.5 years) who
      sustained a hip fracture participated in this study. Linear regression analysis
      was used to determine a statistical model that best predicted gait speed, the
      dependent variable. Gait speed was measured with a computerized gait mat. The
      independent variables were age, sex, height, weight, time post-fracture,
      medications, mental status, depression, balance confidence, Medical Outcome
      Studies, Short Form (SF-36), balance, and lower extremity isometric force. All
      subjects were discharged from physical therapy services, and measurements were
      taken, on average, 17 weeks post-fracture. RESULTS: Using stepwise regression,
      72% of the variance in gait speed was explained by summed lower extremity
      strength normalized by body weight, general health (SF-36), and balance
      confidence (Activities-specific Balance Confidence Scale). CONCLUSIONS:
      Impairments (summed lower extremity strength) and risk factors (perception of
      general health and balance confidence) are important predictors of gait speed in
      elders after hip fracture.

PMID- 20145739
TI  - "Moving Forward": Success from a Physiotherapist's Point of View.
AB  - PURPOSE: The purpose of this study was to capture the meaning of professional
      success to experienced physiotherapists practising in the Greater Toronto Area
      (GTA). METHODS: Using a qualitative, phenomenological approach, 10
      physiotherapists from the GTA each participated in a 60-minute, semistructured,
      face-to-face interview. Interviews were transcribed verbatim and analyzed using
      the vanKaam method, modified by Moustakas. RESULTS: Participants described
      success as "moving forward," a dynamic and evolving experience that extends
      throughout an entire career. Study participants identified three markers of
      professional success: positive patient outcome, career advancement, and
      advancement of the physiotherapy profession. The experience of moving forward
      toward success applied to all of these markers and was driven by making choices.
      Choices made throughout a career were influenced by mentorship and self
      reflection. CONCLUSIONS: The physiotherapists in this study described different
      indicators of success than have been described by other health care or corporate
      professionals in the literature. Success in the physiotherapy profession is
      experienced as a circular rather than linear process. Physiotherapists,
      professional organizations, and employers have a role in fostering professional
      success. We suggest the introduction of mentorship and self-reflection programmes
      early in one's career, focusing on the three markers of success: patient
      outcomes, career advancement, and advancement of the profession.

PMID- 20145740
TI  - Physiological, sensory, and functional measures in a model of wrist muscle injury
      and recovery.
AB  - PURPOSE: To evaluate the effectiveness of muscle rehabilitation modalities, it is
      first necessary to develop a model to test measures that would assess
      physiological, sensory, and functional muscle recovery. This study attempted to
      develop such a model for wrist injury. SUBJECTS: Healthy male and female adults
      (n = 25). METHODS: SUBJECTS performed wrist muscle damage assessment, soreness,
      discomfort, difficulty, and functional motor task tests before and 1, 2, and 7
      days after eccentric wrist muscle contractions. Wrist-related motor task tests,
      including the perception of discomfort and difficulty during performance, were
      also conducted. RESULTS: At 24 hours post-eccentric exercises, wrist extension
      and flexion force declined (p < 0.05) and soreness (p < 0.05) and circumference
      (p < 0.05) increased; all returned to normal by 7 days post-exercise. At 24 and
      48 hours post-exercise, perception of discomfort and difficulty was elevated
      during performance of motor tasks (p < 0.05). The completion speed of motor tasks
      was unaffected at any time post-eccentric exercise (p > 0.05). CONCLUSIONS: Loss
      of wrist muscle force, increased soreness, task discomfort, and difficulty were
      noted following eccentric exercise. However, subjects appeared able to
      compensate, such that the speed of completion of motor tasks was not slowed.
      Longer or more specific motor tasks may be necessary to mimic real work
      performance decrement and recovery.

PMID- 20145742
TI  - Balancing the needs of the population, profession, and self: aligning with the
      environment.

PMID- 20145741
TI  - Theory-based programme development and evaluation in physiotherapy.
AB  - PURPOSE: Programme evaluation has been defined as "the systematic process of
      collecting credible information for timely decision making about a particular
      program." Where possible, findings are used to develop, revise, and improve
      programmes. Theory-based programme development and evaluation provides a
      comprehensive approach to programme evaluation. SUMMARY OF KEY POINTS: In order
      to obtain meaningful information from evaluation activities, relevant programme
      components need to be understood. Theory-based programme development and
      evaluation starts with a comprehensive description of the programme. A useful
      tool to describe a programme is the Sidani and Braden Model of Program Theory,
      consisting of six programme components: problem definition, critical inputs,
      mediating factors, expected outcomes, extraneous factors, and implementation
      issues. Articulation of these key components may guide physiotherapy programme
      implementation and delivery and assist in the development of key evaluation
      questions and methodologies. Using this approach leads to a better understanding
      of client needs, programme processes, and programme outcomes and can help to
      identify barriers to and enablers of successful implementation. Two specific
      examples, representing public and private sectors, will illustrate the
      application of this approach to clinical practice. CONCLUSIONS: Theory-based
      programme development helps clinicians, administrators, and researchers develop
      an understanding of who benefits the most from which types of programmes and
      facilitates the implementation of processes to improve programmes.

PMID- 20145743
TI  - Convergent validity of the constant-murley outcome measure in patients with
      rotator cuff disease.
AB  - PURPOSE: Despite the popularity of the Constant-Murley score (CMS), a combined
      patient-report and objective (health professional administered) shoulder outcome
      measure, minimal information exists on its reliability or validity. The purpose
      of this study was to examine (1) internal consistency and convergent validity of
      the CMS and (2) the degree to which other shoulder measures explain variation in
      range of motion and strength components of the CMS. METHODS: In this cross
      sectional study of outcome measures, 45 patients undergoing conservative or
      surgical treatment for rotator cuff disease participated. Two disease-specific
      outcome measures, one shoulder-specific measure, and one upper extremity outcome
      measure were compared to the CMS. RESULTS: Correlations between competing
      measures and relative total CMS were moderate (0.56 to 0.75). The American
      Shoulder & Elbow Score, the Upper Extremity Functional Index, the Western Ontario
      Rotator Cuff Index, and the Rotator Cuff Quality of Life index explained 38%,
      28%, 26%, and 10% of variance of the objective component of the CMS respectively.
      CONCLUSIONS: The patient-report component of the CMS measures a multidimensional
      concept. The strength component had moderate correlations with isometric strength
      measures of the shoulder external rotators and abductors. The total CMS appears
      to measure a construct that is not totally captured by competing measures. The
      unexplained variance may be due, in part, to the lack of importance of the
      patient's physical impairment to symptoms or activity limitations as measured by
      other instruments.

PMID- 20145744
TI  - Factors associated with physiotherapists' interest in cardiorespiratory
      continuing education using computer-assisted learning: a survey.
AB  - PURPOSE: To determine factors associated with Canadian physiotherapists' interest
      in undertaking continuing education in various cardiorespiratory content areas
      and their willingness to complete a portion of study within each of these content
      areas via computer-assisted learning (CAL). METHODS: In a six-page mailed
      questionnaire, 1,426 potential participants were asked to indicate their interest
      in 11 cardiorespiratory content areas, their continuing-education preferences,
      and their access and willingness to do continuing education by CAL. Demographic
      data were also collected from respondents. RESULTS: Respondents included 285
      physiotherapists from cardiorespiratory interest groups (CRGs) and 447 from the
      licensing bodies' sample (overall response rate = 56%). Physiotherapists in
      public employment and practice areas other than orthopaedics had increased
      interest in all cardiorespiratory content areas except Exercise Physiology.
      Membership in a CRG increased their likelihood to be willing to learn the
      cardiorespiratory content area via CAL. CONCLUSIONS: In developing content and
      determining the accessibility of cardiorespiratory continuing education,
      educators should consider the type of employer and area of practice of interested
      attendees as well as the lack of willingness to use CAL by those not involved in
      CRGs.

PMID- 20145745
TI  - What Does the Cochrane Collaboration Say about Cardiovascular Training?

PMID- 20145746
TI  - Evidence-Based Practice in Women's Health: Making Evidence Come to You!

PMID- 20145747
TI  - Wait times for publicly funded outpatient and community physiotherapy and
      occupational therapy services: implications for the increasing number of persons
      with chronic conditions in ontario, Canada.
AB  - BACKGROUND: Timely access to publicly funded health services has emerged as a
      priority policy issue across the continuum of care from hospitals to the home and
      community sector. The purpose of this study was to examine wait lists and wait
      times for publicly funded outpatient and community occupational therapy (OT) and
      physical therapy (PT) services. METHODS: A mailed self-administered questionnaire
      was sent in December 2005 to all publicly funded sites across Ontario that
      deliver outpatient or community OT or PT services (N = 374). Descriptive
      statistics were used to describe the study sample and to examine wait lists and
      wait times by setting and client condition. RESULTS: Overall response rate was
      57.2% (n = 214). More than 10,000 people were reported to be waiting for OT or PT
      services across Ontario. Of these, 16% (n = 1,664) were waiting for OT and 84% (n
      = 8,842) for PT. Of those waiting for OT, 59% had chronic conditions and half
      were waiting for home care rehabilitation services. Of those waiting for PT, 73%
      had chronic conditions and 81% were waiting at hospital outpatient departments.
      CONCLUSIONS: Individuals with chronic conditions experience excessive wait times
      for outpatient and community OT and PT services in Ontario, particularly if they
      are waiting for services in hospital outpatient departments.

PMID- 20145748
TI  - Understanding the professional socialization of canadian physical therapy
      students: a qualitative investigation.
AB  - PURPOSE: To understand the professional socialization of physical therapy (PT)
      students. METHOD: Forty-two students enrolled in our newly developed master's
      degree programme wrote three-page reflective journals on a critical learning
      incident after each of three selected clinical experiences. The journals were
      coded and analyzed, and major themes were identified and described. A separate
      cohort of 44 students participated in focus groups after the same three clinical
      experiences to check the trustworthiness of the results. RESULTS: Following the
      first placement, the main themes coded were emotions, self-confidence,
      professionalism in the real world, communication, and learning by doing. After
      the intermediate placement, major themes were idealism versus realism, depth of
      communication with clients, and breadth of communication with family members and
      colleagues. Aspects of clinical learning were variable, and self-confidence
      remained an issue. After the final placement, most students were deeply engaged
      with their clients and self-confidence had developed to the point of self
      efficacy. Tensions increased between the concept of ideal practice and the
      pragmatics of actual practice, and the concept of self as protege (rather than as
      object of the supervisor's evaluation) emerged. The themes were subsequently
      assembled in a booklet with representative quotations. CONCLUSION: These results
      contribute to foundational knowledge required by PT educators, including clinical
      instructors, by explicitly describing the professional socialization of PT
      students.

PMID- 20145749
TI  - Management of fall-related injuries in the elderly: a retrospective chart review
      of patients presenting to the emergency department of a community-based teaching
      hospital.
AB  - PURPOSE: To identify current practice for elderly individuals who have sustained
      a fall-related injury and subsequently presented to the emergency department (ED)
      of a community-based hospital in Toronto, Ontario. METHODS: A retrospective
      longitudinal chart review was conducted for 300 persons, 65 years of age and
      older, who presented to the ED of a community-based teaching hospital with a fall
      from June 2004 through May 2005. Data were collected using a tool created by the
      investigators (based on information gathered through a literature review) to
      capture information related to risk factors for falling. RESULTS: Our study
      sample was demographically similar to elderly individuals in other fall-related
      studies. Most patients discharged directly from the ED did not receive
      multidisciplinary care. In the ED, all patients saw a nurse or physician, while
      only 1.3% (n = 4) saw a physical therapist, 3.0% (n = 9) saw an occupational
      therapist, and 5.3% (n = 16) saw a social worker. At discharge, 62% (n = 152) had
      no documented referral for follow-up care. Abilities related to falls in elderly
      individuals were not consistently assessed in the ED. Frequency of assessment for
      these abilities was as follows: (1) gait, 10.2%; (2) balance, 4.1%; (3) lower
      extremity range of motion, 4.9%; (4) lower-extremity strength, 2.0%; (5)
      cognition, 26.1%; (6) vision, 2.0%; (7) ability to perform activities of daily
      living, 7.3%. In the 6 months following the index fall, 8.3% of patients returned
      to the ED of the same hospital because of a subsequent fall. CONCLUSIONS: In the
      ED, fall-related risk factors were not consistently assessed or documented, and
      few patients received multidisciplinary management. Since elderly individuals who
      fall commonly present to the ED, the implementation of evidence-based strategies
      aimed at preventing repeat falls should be considered.

PMID- 20145751
TI  - What Does the Cochrane Collaboration Say about Exercises for the Hip and Knee?

PMID- 20145750
TI  - Relationship between Preoperative Patient Characteristics and Expectations in
      Candidates for Total Knee Arthroplasty.
AB  - PURPOSE: The purpose of this study was to determine the relationship between
      patient expectations for improvement following primary total knee arthroplasty
      (TKA) and patient preoperative characteristics. METHODS: This was a cross
      sectional analysis of preoperative expectations. Expectations for improvement
      were evaluated in six distinct domains. The baseline factors used as independent
      variables were age, gender, presence of comorbidity, sub-domains of the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC; pain, stiffness,
      physical limitation related to lower extremity), and SF-36 physical and mental
      health component scores. Stepwise logistic regression analysis was applied to
      examine the relationships between dependent and independent variables. RESULTS:
      The study cohort consisted of 236 candidates for TKA (154 women and 82 men, mean
      age 67, SD = 9.98). Expectations were high on average. Presence of comorbidity
      was associated with expectations of pain relief. Preoperative mental health was
      related to expectations for a return to activities of daily living; age, gender,
      physical health, and mental health were related to expectations for improved
      leisure, recreational, and sports activities. Preoperative physical health was
      related to expectations for potential return to full recovery. No baseline
      factors were associated with expectations for improved range of motion or for
      providing care to and interacting with others. CONCLUSION: Expectations related
      to recovery from surgery appeared to have distinct dimensions and were associated
      with patient baseline characteristics.

PMID- 20145752
TI  - Letter to the editor.

PMID- 20145753
TI  - Web 2.0 in physical therapy: a practical overview.

PMID- 20145754
TI  - Efficacy of postural and neck-stabilization exercises for persons with acute
      whiplash-associated disorders: a systematic review.
AB  - PURPOSE: We systematically reviewed randomized and quasi-randomized clinical
      trials in the literature to assess the efficacy of neck stabilization and
      postural exercises on pain, neck range of motion, and time off work in adults
      with acute whiplash-associated disorders. METHODS: Electronic databases,
      reference lists of relevant Cochrane reviews, reference lists of studies selected
      for inclusion, and tables of contents of relevant journals were systematically
      searched for randomized and quasi-randomized controlled trials. Two independent
      reviewers selected studies for inclusion, assessed methodological quality, and
      extracted data. Because of the heterogeneity of the interventions, a qualitative
      synthesis was performed using "levels of evidence" as recommended by van Tulder
      et al. RESULTS: Eight studies representing five clinical trials were selected for
      inclusion. Two trials were graded as high quality, two as moderate quality, and
      one as low quality. Many of these studies had mixed results, demonstrating
      significant differences on some outcome measures but not on others. CONCLUSIONS:
      There is moderate evidence to support the use of postural exercises for
      decreasing pain and time off work in the treatment of patients with acute
      whiplash-associated disorders. However, no evidence exists to support the use of
      postural exercises for increasing neck range of motion. There is conflicting
      evidence in support of neck stabilization exercises in the treatment of patients
      with acute whiplash-associated disorders.

PMID- 20145755
TI  - Clinical specialists and advanced practitioners in physical therapy: a survey of
      physical therapists and employers of physical therapists in ontario, Canada.
AB  - PURPOSE: Opportunities to expand the role of physical therapists (PTs) have
      evolved to include clinical specialists and advanced practitioners, although the
      literature on these roles is limited. We examined perceptions of PTs and PT
      employers in Ontario regarding clinical specialization and advanced practice.
      METHODS: Using a modified Dillman approach, a cross-sectional survey was
      conducted with 500 PTs and 500 PT employers in Ontario. Questionnaires were
      tailored to address specific issues related to each cohort. RESULTS: Sixty
      percent of PTs and 53% of PT employers responded to the survey. Thirty-three
      percent of PT respondents already considered themselves "clinical specialists"
      (CS), and 8% considered themselves "advanced practitioners" (AP), although
      neither role is yet formally recognized in Canada. Both groups had substantial
      interest in pursuing formal recognition of CS and AP status. Respondents
      indicated that their primary motivation to pursue such roles was to enhance
      clinical reasoning skills with the goal of improving client outcomes (82% for the
      role of CS, 71% for the role of AP). Respondents supported the involvement of
      academic institutions in the process (60% for CS, 70% for AP). CONCLUSION: PTs
      and PT employers are supportive of the roles of the CS and AP within the
      profession, even though there is currently no formal recognition of either role
      in Canada.

PMID- 20145756
TI  - Pain profiles and psychosocial distress symptoms in workers with low back pain.
AB  - PURPOSE: The current study investigated the pain profiles of patients with
      subacute non-specific low back pain attending an outpatient return-to-work
      rehabilitation programme. Differences in symptoms of distress (depression and
      anxiety) and return to work between the pain-profile groups were assessed.
      METHODS: Sixty-five volunteers who met the eligibility criteria and had complete
      follow-up data were included in the analysis. The mean age was 38.8 years
      (minimum 18, maximum 64); 38 (58.5%) were men. The median time since onset of low
      back pain was 30 days. Cluster analysis was used to categorize patients into
      groups according to pain severity scores (VAS). RESULTS: Two distinct clusters
      severe pain and moderate pain-emerged. There were significant differences in
      depressive and anxiety symptoms between the pain profiles. Further, return-to
      work rates varied significantly between the two groups (31% in the severe pain
      cluster compared to 90% in the moderate pain cluster). CONCLUSION: Although both
      groups showed significant improvements in depression and anxiety symptoms over
      time, the severe pain cluster scored higher at discharge (higher scores
      indicating worse outcomes). These results highlight the importance of early
      identification of sub-groups at risk so that rehabilitation interventions can be
      focused with the goal of minimizing long-term disability.

PMID- 20145757
TI  - Availability and structure of ambulatory rehabilitation services: a survey of
      hospitals with designated rehabilitation beds in ontario, Canada.
AB  - PURPOSE: To determine the degree to which ambulatory physical therapy (PT),
      occupational therapy (OT), and speech language pathology (SLP) services are
      available in hospitals with designated rehabilitation beds (DRBs) in Ontario, and
      to explore the structure of delivery and funding among services that exist.
      METHODS: Questions regarding ambulatory services were included in the System
      Integration and Change (SIC) survey sent to all hospitals participating in the
      Hospital Report 2005: Rehabilitation initiative. RESULTS: The response rate was
      75.9% (41 of 54 hospitals). All hospitals surveyed provide some degree of
      ambulatory rehabilitation services, but the nature of these services varies
      according to rehabilitation client groups (RCGs). The majority of hospitals
      continue to deliver services through their employees rather than by contracting
      out or by creating for-profit subsidiary clinics, but an increasing proportion is
      accessing private sources to finance ambulatory services. CONCLUSIONS: Most
      hospitals with DRBs provide some degree of ambulatory rehabilitation services.
      Privatization of delivery is not widespread in these facilities.

PMID- 20145758
TI  - Measurement properties of performance-specific pain ratings of patients awaiting
      total joint arthroplasty as a consequence of osteoarthritis.
AB  - PURPOSE: To estimate the test-retest reliability of the Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) pain sub-scale and performance
      specific assessments of pain, as well as the association between these measures
      for patients awaiting primary total hip or knee arthroplasty as a consequence of
      osteoarthritis. METHODS: A total of 164 patients awaiting unilateral primary hip
      or knee arthroplasty completed four performance measures (self-paced walk, timed
      up and go, stair test, six-minute walk) and the WOMAC. Scores for 22 of these
      patients provided test-retest reliability data. Estimates of test-retest
      reliability (Type 2,1 intraclass correlation coefficient [ICC] and standard error
      of measurement [SEM]) and the association between measures were examined.
      RESULTS: ICC values for individual performance-specific pain ratings were between
      0.70 and 0.86; SEM values were between 0.97 and 1.33 pain points. ICC estimates
      for the four-item performance pain ratings and the WOMAC pain sub-scale were 0.82
      and 0.57 respectively. The correlation between the sum of the pain scores for the
      four performance measures and the WOMAC pain sub-scale was 0.62. CONCLUSION:
      Reliability estimates for the performance-specific assessments of pain using the
      numeric pain rating scale were consistent with values reported for patients with
      a spectrum of musculoskeletal conditions. The reliability estimate for the WOMAC
      pain sub-scale was lower than typically reported in the literature. The level of
      association between the WOMAC pain sub-scale and the various performance-specific
      pain scales suggests that the scores can be used interchangeably when applied to
      groups but not for individual patients.

PMID- 20145759
TI  - Development of a Walking Safety Scale for Older Adults, Part I: Content Validity
      of the GEM Scale.
AB  - PURPOSE: The Grille d'evaluation de la securite a la marche (GEM scale) is a
      performance-based tool developed to fill the need for an objective assessment of
      walking safety for older adults. It underwent a three-phase process of content
      validation. METHOD: A mailed questionnaire was used to assess the
      representativeness of the walking items (5-point pertinence scale). Subsequently,
      two physiotherapist focus groups (n = 20) were held to further evaluate the
      relevance of the scale and the walking items. Finally, a pilot study was
      completed with 3 raters administering the GEM scale to 12 hospitalized patients.
      RESULTS: Comments and descriptive statistics (percentages) were analyzed from the
      questionnaire results and focus groups. On completion of the pilot study, which
      assessed 12 patients on the GEM scale, additional analyses were performed to
      address the theoretical background, the administration manual, the walking items,
      the scoring scale, and interpretation of the scale. Following each step,
      modifications were made to reflect the results of the analyses. CONCLUSION: The
      three-phase content-validation process demonstrated the relevance of this
      instrument and its representativeness as a walking safety assessment tool for
      older adults.

PMID- 20145760
TI  - Development of a Walking-Safety Scale for Older Adults, Part II: Interrater and
      Test-Retest Agreement of the GEM Scale.
AB  - PURPOSE: The GEM scale is an objective assessment tool, specifically developed
      for older adults, to evaluate walking safety using standardized tasks. The
      purpose of this study was to estimate the interrater and test-retest agreement of
      the GEM scale. METHOD: Participants (n = 41; >/= 65 years) were recruited from
      geriatric units and assessed independently and simultaneously by three raters on
      two occasions using the GEM scale. Kappa coefficients and percentage agreement
      were calculated for each item of the scale. RESULTS: A majority of walking items
      (n = 22) showed fair to substantial interrater agreement (kappa >/= 0.25) and
      substantial to almost perfect test-retest agreement (kappa >/= 0.60). Mean
      percentage agreement was high for both interrater and test-retest agreement (79%
      +/- 15% and 83% +/- 16% respectively). Moreover, detailed analyses demonstrated
      that the relatively low agreement of some items resulted from changes in the
      performance of some participants and the low variability of scores. Although some
      walking items showed less agreement, the final decision regarding the
      participants' ability to walk safely resulted in moderate to substantial
      interrater and test-retest agreement. CONCLUSION: The GEM scale is a new
      assessment tool that can now be used with estimated interrater and test-retest
      properties to allow therapists to objectively evaluate walking safety among the
      elderly.

PMID- 20145761
TI  - What Does the Cochrane Collaboration Say about Adult Client/Patient Education?

PMID- 20145762
TI  - Can Patient Testimonials Constitute Evidence? Plantar Fasciitis-Part II.

PMID- 20145763
TI  - A Randomized Clinical Trial of Aquatic versus Land Exercise to Improve Balance,
      Function, and Quality of Life in Older Women with Osteoporosis.
AB  - PURPOSE: Despite the decreased gravitational loading that is experienced in an
      aquatic environment, little research has been conducted on this exercise medium
      for women with osteoporosis (OP). Aquatic exercise (AE) may improve function and
      balance, thus ultimately decreasing fall risk and the potential for hip fractures
      in this high-risk population. METHOD: A total of 68 women with OP, aged 60 years
      or older, were recruited into a randomized clinical trial evaluating the impact
      of AE, land exercise (LE), and no exercise (NE) on balance, functional mobility,
      and quality of life (QOL). RESULTS: Only one balance measure (backward tandem
      walk) significantly improved with AE compared to LE, but this did not translate
      into a greater improvement in self-report function. There were no significant
      differences between the exercise interventions and NE, except for in ratings of
      global change, where participants in the AE group were three times more likely to
      report improvement than those in the NE group. CONCLUSION: There were no
      differences in balance, function, or QOL in women with OP who followed an AE or
      LE programme compared to those in an NE control group. However, the significant
      differences in backward tandem walk between the AE and LE groups and self
      reported global change between the AE and NE groups warrant further
      investigation. Significant improvements in balance and global change suggest that
      AE is a viable alternative for older women with OP who have difficulty exercising
      on land.

PMID- 20145764
TI  - Specific directional exercises for patients with low back pain: a case series.
AB  - PURPOSE: To determine whether outcomes could be changed after poor response to
      non-specific exercise therapy when the prescription was changed to specific,
      directional-preference exercises (McKenzie method). METHODS: Patients who
      participated in a randomized clinical trial (RCT) and the alternative care phase
      immediately following formed the cohort for this case series. In an earlier RCT,
      patients with directional preference were randomized to exercises/advice matched
      to their individual directional preference or to one of two unmatched protocols.
      The primary inclusion criterion for our case series was patient reports of being
      unchanged or worse following 2 weeks' treatment in the RCT. The secondary
      inclusion criterion was patient requests for "a change to one of the other
      stretching protocols to see if I can achieve better pain control." Patients
      meeting either of these criteria were offered matched exercises/advice if they
      had not previously received this intervention. Two-way repeated-measures ANOVA
      and McNemar tests compared outcomes during two consecutive time intervals:
      baseline to 2 weeks and 2 weeks to discharge. Dropouts were included in the
      intention-to-treat analysis. RESULTS: Four patients from the matched group met
      the primary inclusion criterion of "unchanged" (none reported being worse); 10
      additional patients requested alternative treatment for better pain control
      (secondary criterion). Eighty-five patients from the two unmatched treatment
      groups met all the inclusion criteria, and an additional 22 patients met only the
      secondary criterion. These patients were offered matched treatment, and 96
      consented. Those reporting improvement or resolution of symptoms were 22 % in the
      first two weeks of unmatched care (during the RCT) compared to 84 % with matched
      care. Statistically significant and clinically meaningful changes occurred in all
      outcomes (p < 0.001) after receiving matched care, compared to clinically
      unimportant changes with previous unmatched care during the RCT. CONCLUSIONS:
      Poor outcomes from non-specific/unmatched exercise protocols appeared to reverse
      when patients with directional preference were given sub-group-matched, direction
      specific exercises. Because of the limitations of our study design, replication
      with a control group and longer-term follow-up are required to validate the
      findings.

PMID- 20145765
TI  - Physiotherapy-leadership and opportunities.

PMID- 20145766
TI  - Investigation of the frequency and force of chest vibration performed by
      physiotherapists.
AB  - PURPOSE: To investigate the frequency and force of chest vibration as applied by
      18 physiotherapists working in a teaching hospital. METHOD: CHEST VIBRATION WAS
      APPLIED TO A HEALTHY ADULT MALE LYING SUPINE ON A PLINTH WITH SEVEN MOUNTED
      SENSORS MEASURING FREQUENCY AND FORCE, DURING THREE TEST CONDITIONS: (1) directly
      on the chest, (2) on the chest through a layer of sheet, and (3) on the chest
      through a layer of towelling. The influence of gender and current practice area
      (physiotherapists working in cardiopulmonary areas [cardiopulmonary
      physiotherapists] and physiotherapists who presently did not work in the
      cardiopulmonary area, but had treated cardiopulmonary patients within the last
      year [general practice physiotherapists]) on the frequency and force of chest
      vibrations was examined. RESULTS: Physiotherapists demonstrated a mean frequency
      of 5.7, 5.3, and 5 Hz and a mean maximum force of 272.78, 273.47, and 271.13 N
      for conditions 1, 2, and 3 respectively. There were no significant differences in
      the frequency or forces generated by vibration between cardiopulmonary and
      general practice physiotherapists, between genders, or among the three test
      conditions. CONCLUSIONS: Vibration frequency was lower and force higher than
      previously recorded. Force may vary depending on the patient. The addition of a
      sheet or towel did not affect the force or frequency of vibration compared to
      vibration performed directly on the chest.

PMID- 20145767
TI  - Perceptions of outpatients regarding the attire of physiotherapists.
AB  - PURPOSE: This study investigated perceptions of patients regarding
      physiotherapists' attire. METHODS: Three hundred patients in three publicly
      funded outpatient physiotherapy clinics were asked to complete a questionnaire,
      ranking four photographed modes of attire (lab coat, tailored dress, "scrubs,"
      and jeans) in terms of professionalism, preference, and appropriateness and
      rating their level of agreement with four statements about physiotherapists'
      attire. RESULTS: Response rate was 63.7 %. The lab coat was ranked most
      professional, tailored dress most preferred, and jeans least professional and
      least preferred. Although jeans were deemed inappropriate (p < 0.001), strong
      support was shown for wearing jeans on "casual day" (p = 0.001). Age of
      respondents influenced the perception of the appropriateness of wearing jeans (p
      = 0.007 for male therapist; p = 0.017 for female therapist); only the cohort <36
      years considered jeans appropriate apparel. Overall exposure to physiotherapists
      (number of lifetime visits) affected patients' perceptions of the importance of
      attire (p = 0.039) and the appropriateness of wearing jeans (p = 0.018): as
      number of visits increased, perceived importance decreased and perceived
      propriety of jeans increased. CONCLUSION: The findings of this study, the first
      to examine patients' opinions of physiotherapists' attire, suggest that
      outpatients made clear distinctions between what they perceived as professional
      and what they preferred, as well as between the appropriateness of
      physiotherapists' wearing jeans in general and the appropriateness of their doing
      so on "casual day." Age and exposure to physiotherapists influenced patients'
      perceptions of attire.

PMID- 20145769
TI  - Clinician's Commentary.

PMID- 20145768
TI  - Exercise for fall risk reduction in community-dwelling older adults: a systematic
      review.
AB  - PURPOSE: To evaluate the influence of exercise on falls and fall risk reduction
      in community-dwelling older adults and to present an updated synthesis of outcome
      measures for the assessment of fall risk in community-dwelling older adults.
      METHOD: A systematic review was performed, considering English-language articles
      published from 2000 to 2006 and accessible through MEDLINE, CINAHL, PEDro,
      EMBASE, and/or AMED. Included were randomized controlled clinical trials (RCTs)
      that used an exercise or physical activity intervention and involved participants
      over age 50. Screening and methodological quality for internal validity were
      conducted by two independent reviewers. RESULTS: The search retrieved 156
      abstracts; 22 articles met the internal validity criteria. Both individualized
      and group exercise programmes were found to be effective in reducing falls and
      fall risk. The optimal type, frequency, and dose of exercise to achieve a
      positive effect have not been determined. A variety of outcome measures have been
      used to measure fall risk, especially for balance. CONCLUSIONS: Falls and fall
      risk can be reduced with exercise interventions in the community-dwelling
      elderly, although the most effective exercise variables are unknown. Future
      studies in populations with comorbidities known to increase fall risk will help
      determine optimal, condition-specific fall-prevention programmes. Poor balance is
      a key risk factor for falls; therefore, the best measure of this variable should
      be selected when evaluating patients at risk of falling.

PMID- 20145770
TI  - The most accessed cochrane reviews.

PMID- 20145771
TI  - Letter Re: Winter 2008 Editorial, "Plantar Fasciitis: What's An Evidence-Informed
      Consumer To Do?".

PMID- 20145772
TI  - Indexes.

PMID- 20145773
TI  - Objective versus Subjective: Kudzu Terminology.

PMID- 20145774
TI  - Use of outcome measures in physiotherapy practice in ireland from 1998 to 2003
      and comparison to canadian trends.
AB  - PURPOSE: The purposes of this study were to examine changes in the use of
      standardized outcome measures by practising physiotherapists in Ireland and to
      compare those trends to the results of a similar survey conducted previously in
      Canada. METHOD: A survey methodology was employed. The review of practice
      occurred at two points in time. Senior clinical physiotherapists working with
      older people participated. Questions were asked about the use of standardized
      outcome measures, the nature and pattern of their use, and the level of
      confidence the respondents had in using such measures. RESULTS: The results chart
      the changes in practice over a 5-year period. Although there was an increase in
      the use of standardized outcome measures, the respondents acknowledged barriers
      to their systematic use in routine practice (e.g., lack of time,
      resources/administrative support). There was a lack of professional consensus on
      what instruments to use in general, as well as which to use for particular client
      groups. Concern was expressed that none of the available instruments met their
      clients' needs. Where possible and appropriate, comparison was made between the
      data from the 2003 Irish study and a survey of Canadian physiotherapists
      conducted in 1998. CONCLUSION: This review of practice illustrates that changes
      that have occurred in Ireland in the use of standardized outcome measures are
      similar to those that have occurred in Canada, but barriers remain to their
      complete integration into clinical practice and clinical decision making.

PMID- 20145775
TI  - Self-Assessment: The Disconnect between Research and Rhetoric.
AB  - PURPOSE: Physical therapists are expected to engage in self-assessment in order
      to ensure competent practice and to identify appropriate professional development
      activities. SUMMARY OF KEY POINTS: This paper reviews the current literature on
      the accuracy and role of self-assessment in physical therapy. Current literature
      indicating that self-assessment cannot be conducted with any degree of accuracy
      is discussed, and a proposed reformulation of the concept of self-assessment is
      presented. RECOMMENDATIONS: Practical strategies are offered for clinicians to
      improve the potential for obtaining reliable and valid information about their
      own clinical performance to guide the selection of appropriate professional
      development activities and to promote the provision of competent patient care.

PMID- 20145776
TI  - Factors contributing to failure of rotator cuff surgery in persons with work
      related injuries.
AB  - PURPOSE: Shoulder pain is a major musculoskeletal and economic concern in
      industrialized countries, with the rate of surgical failure reportedly higher in
      patients injured at work. The purposes of this study were (1) to examine the
      prevalence of identifiable causes of rotator cuff surgery failure and (2) to
      examine the relationship among the existence of these causes and outcome scores,
      patient expectations, and overall satisfaction. METHODS: This was a cross
      sectional study of patients who experienced continued impairments following
      surgical treatment for work-related injuries. The primary outcome was a disease
      specific measure, the Western Ontario Rotator Cuff (WORC) index. Patients were
      categorized into two groups based on the existence of an identifiable reason for
      surgical failure vs. no reason for failure, as demonstrated by clinical and
      radiologic investigations and decided upon by a shoulder surgeon and a physical
      therapist. Analyses included a t-test for independent sample means, linear
      regression, non-parametric Wilcoxon test, and Fisher's exact test. RESULTS:
      Thirty-eight consecutive patients were included in the study, and 24 causes of
      surgical failure were identified in 19 patients (50%). Overall, patients with
      findings of failure were more disabled according to the total WORC index and had
      higher levels of symptoms, emotional difficulties, and limitations in sports and
      recreational activities. Expectations and satisfaction levels were not
      significantly different between groups. CONCLUSION: Our results indicate that 50%
      of patients who reported failed surgery had at least one reason to explain their
      ongoing symptoms, emotional difficulties, and functional limitations.

PMID- 20145777
TI  - Effects of exercise interventions on stereotypic behaviours in children with
      autism spectrum disorder.
AB  - PURPOSE: The purpose of this systematic review was to synthesize evidence from
      studies examining the effect of exercise interventions on stereotypic behaviours
      in children with autism spectrum disorder (ASD). METHODS: Only exercise-related
      physical therapy (PT) interventions were included. A multifaceted search strategy
      identified studies published between 1980 and 2007. Quality was assessed using
      the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) Study
      Quality Scale, the Clinical Relevance Tool for Case Studies, and the Quality,
      Rigour or Evaluative Criteria tool. RESULTS: Seven studies (1982-2003) met our
      inclusion criteria; four of these used single-subject research designs, two were
      group studies, and one was a case study. Ages and behavioural characteristics of
      the children (N = 25) varied among the studies. Levels of evidence ranged from II
      to V (of a possible I-V). Study quality scores ranged from 2 to 5 (range: 0 to
      7); mean = 3.9, mode = 5. Few studies in this area of PT practice have been
      published, and those identified scored low levels of rigour on the AACPDM
      criteria. CONCLUSIONS: Research suggests that exercise provides short-term
      reductions of stereotypic behaviours in children with ASD. Future research with
      stronger evidence levels, greater rigour, and longer-term outcome assessment is
      required to determine specific exercise parameters.

PMID- 20145778
TI  - Eccentric exercise in patients with chronic health conditions: a systematic
      review.
AB  - PURPOSE: The capacity of eccentric actions to produce muscle hypertrophy,
      strength gains, and neural adaptations without stressing the cardiopulmonary
      system has led to the prescription of eccentric training programmes in patients
      with low tolerance to exercise, such as elders or those with chronic health
      conditions. The purpose of this systematic review was to analyze the evidence
      regarding the effectiveness and suitability of eccentric training to restore
      musculoskeletal function in patients with chronic diseases. SUMMARY OF KEY
      POINTS: Relevant articles were identified from nine databases and from the
      reference lists of key articles. Articles were assessed to determine level of
      evidence and scientific rigour. Nine studies met the inclusion criteria.
      According to Sackett's levels of evidence, 7 studies were graded at level IIb, 1
      study at level IV, and the remaining study at level V. Articles were also graded
      for scientific rigour according to the PEDro scale. One study was rated as high
      quality, 4 studies were rated as moderate, and 2 studies were graded as poor
      quality. CONCLUSIONS: Eccentric training may be safely used to restore
      musculoskeletal function in patients with some specific chronic conditions.
      However, the heterogeneity of diseases makes it very difficult to extrapolate
      results and to standardize clinical recommendations for adequate implementation
      of this type of exercise. More studies are needed to establish the potential
      advantages of eccentric training in chronic conditions.

PMID- 20145779
TI  - Constraint-induced movement therapy for severe upper-extremity impairment after
      stroke in an outpatient rehabilitation setting: a case report.
AB  - PURPOSE: Laboratory studies confirm that constraint-induced movement therapy
      (CIMT) improves upper-extremity (UE) function after stroke. Due to strict patient
      criteria and the intensive resources required, CIMT has been slow to become part
      of rehabilitation practice. Our purpose was to determine the feasibility and
      effectiveness of an adapted experimental protocol within an outpatient clinical
      setting for a patient with moderate to severe UE impairment who did not meet
      traditional CIMT criteria. PATIENT DESCRIPTION: AJ, a 16-year-old male,
      experienced a left middle cerebral artery ischemic stroke due to carotid artery
      dissection one year before beginning CIMT. He demonstrated some proximal movement
      but no wrist or finger extension. He had received intensive rehabilitation for 12
      months prior to beginning CIMT. INTERVENTION: Two occupational therapists and two
      physiotherapists collaborated to provide CIMT task training for 6 hours daily for
      2 weeks. A knitted mitten extending to the elbow restrained the less-involved UE
      during 90% of waking hours. Tasks were tailored to AJ's interests, with the goal
      of integrating his affected UE into his behavioural repertoire. MEASURES AND
      OUTCOMES: After 2 weeks of CIMT, AJ improved in all measures (grip and lateral
      pinch strength, Action Research Arm Test [ARAT], and Box and Block Test) except
      the Chedoke McMaster Impairment Inventory. Greatest gains were seen at 6 months
      in the ARAT and Box and Block Test, which coincided with patient and family
      reports of AJ's using his arm in everyday functional tasks. IMPLICATIONS: Shared
      workload, emphasis on relevant functional tasks, and complete family
      participation likely influenced the success of CIMT. Our findings suggest that
      the strict CIMT criteria used in previous studies may exclude patients who might
      benefit from the treatment. Controlled trials should be undertaken to examine the
      effects of CIMT in patients with moderate to severe UE impairment.

PMID- 20145780
TI  - Profile of patients at admission into an inpatient stroke rehabilitation
      programme: cardiorespiratory fitness and functional characteristics.
AB  - PURPOSE: The purposes of this study were to characterize the cardiorespiratory
      capacity of individuals on admission to inpatient rehabilitation following stroke
      and to examine the relationship between measures of cardiorespiratory capacity
      and standard indices of neurological deficit and functional status. METHODS: We
      recruited 45 patients within the first 10 days of admission to rehabilitation. We
      performed measures of aerobic fitness (VO(2)peak), functional status (Functional
      Independence Measure [FIM] and Clinical Outcomes Variable Score [COVS]), and
      neurological deficit (National Institutes of Health Stroke Scale [NIHSS] and
      Chedoke-McMaster Stroke Assessment scale [CMSA]). RESULTS: Nineteen women and 26
      men with a mean (SD) age of 65.2 (14.5) years were admitted to rehabilitation
      16.2 (11.9) (minimum 3, maximum 62) days post-stroke. Average VO(2)peak was less
      than half the value expected in age-matched healthy individuals at 11.1 (3.1)
      ml/kg/min. The associations between VO(2)peak and FIM, NIHSS, and COVS were weak
      (r = 0.25, -0.12, and 0.26 respectively, p = 0.12, 0.46, and 0.10 respectively).
      There were no differences in VO(2)peak in higher-functioning individuals with
      CMSA leg scores of 5 and 6 compared to lower-functioning individuals with scores
      of 3 and 4 (p = 0.30). CONCLUSION: Cardiorespiratory capacity is extremely low in
      individuals during the first 3 months after stroke. Alternative measures of
      functional or clinical status do not adequately reflect this cardiorespiratory
      state; thus, routine measurement of cardiorespiratory capacity should be
      considered, along with a risk-factor profile.

PMID- 20145781
TI  - Effects of Multi-modal Physiotherapy, Including Hip Abductor Strengthening, in
      Patients with Iliotibial Band Friction Syndrome.
AB  - PURPOSE: The purposes of this study were to quantitatively examine hip abductor
      strength in patients presenting with iliotibial band friction syndrome (ITBFS)
      and to determine whether a multi-modal physiotherapy approach, including hip
      abductor strengthening, might play a role in recovery. METHOD: Our observational,
      pretest-posttest study is one of the first prospective studies in this area.
      Patients presenting to physiotherapy with unilateral ITBFS were recruited to
      participate. Participants followed a 6-week rehabilitation programme designed to
      strengthen hip abductors; strength was measured every 2 weeks using a hand-held
      dynamometer and compared bilaterally. RESULTS: Sixteen subjects (five men, 11
      women) aged 20 to 53 years participated. All but 2 reported running as one of
      their main physical activities. A trend toward a significant difference in hip
      abductor strength was found between the injured and uninjured sides at baseline,
      but this difference disappeared by 6 weeks. Hip abductor strength was
      significantly related to physical function at weeks 2, 4, and 6. Nine subjects
      were discharged from physiotherapy after the 6-week period, while the other 7
      subjects continued attending for up to 5 months. CONCLUSIONS: Hip abductor
      strengthening appeared to be beneficial in the treatment of ITBFS, but further
      research on the use of hip abductor strengthening for treatment and prevention of
      ITBFS is needed.

PMID- 20145782
TI  - What Does the Cochrane Collaboration Say about Neck Disorders?

PMID- 20145783
TI  - Will granny be able to get her rotator cuff repaired?

PMID- 20145784
TI  - An arthroscopic-plus-open method of repair for combined tears of the
      subscapularis, supraspinatus, and infraspinatus tendons.
AB  - Tears involving the subscapularis and posterosuperior rotator cuff comprise a
      distinct clinical entity. An aggressive treatment involving operative repair has
      demonstrated superior results compared with delayed intervention, yet there is no
      consensus as to the optimal method of repair. Various methods are evolving, but
      they are not without their pitfalls. Methods of fixation, patient positioning,
      and biceps management are emerging as points of contention. In this technical
      note, we describe an arthroscopic-plus-open approach in which arthroscopic repair
      of the posterosuperior rotator cuff is followed by an open subscapularis repair.
      Advantages of this method include ability to address concomitant pathology,
      relative ease of repair, and creation of a strong, reliable construct. The
      interval-splitting approach affords minimal additional morbidity and does not
      preclude use of allograft or biological augmentation for salvage procedures.
      Overall, this method is an effective, efficient technique that yields
      reproducible, reliable repair of these combined rotator cuff tears.

PMID- 20145785
TI  - Hip fracture outcome: is there a "July effect"?
AB  - We assessed the differential complications and mortality rates of teaching versus
      nonteaching hospitals in July against other month-to-month differences in a
      cohort of 324,988 elderly patients hospitalized for a femoral neck or
      intertrochanteric fracture (data taken from the 1998-2003 National Inpatient
      Sample). Demographics were similar between teaching and nonteaching hospitals and
      across admission months. The overall mortality rate was 3.64% and was slightly
      higher in teaching hospitals compared with nonteaching hospitals (3.69% vs.
      3.61%, relative risk [RR] = 1.0062, 95% CI 0.99-1.02). The adjusted relative risk
      (RR) for mortality in July/August was significantly higher than the overall
      adjusted RR and compared with all other month pairs, indicating higher in
      hospital mortality rates in teaching hospitals compared with nonteaching
      hospitals. Intraoperative complications and length of stay were statistically
      significantly greater in teaching hospitals but did not demonstrate a "July
      effect." Teaching hospitals had lower perioperative complication rates. Elderly
      hip fracture patients treated at teaching hospitals had 12% greater relative risk
      of mortality in July/August (ie, experience a "July effect") compared with
      nonteaching hospitals during that time period (1998-2003). Although various
      methods exist for exploring the "July effect," it is critical to take into
      account inherent month-to-month variation in outcomes and to use nonteaching
      hospitals as a control group.

PMID- 20145786
TI  - Randomized prospective evaluation of adjuvant hyaluronic acid therapy
      administered after knee arthroscopy.
AB  - Intra-articular injections of hyaluronic acid products may eliminate pain,
      improve mobility and quality of life, and delay osteoarthritis progression. In
      this study, we evaluated the safety and efficacy of sodium hyaluronate injections
      given after knee arthroscopy. Forty-six patients with early osteoarthritis and a
      symptomatic meniscus tear were prospectively randomized into study (injection)
      and control groups and underwent knee arthroscopy. Study patients received 3
      sodium hyaluronate injections after surgery. Study and control outcomes were
      compared 3 and 6 months after surgery. The injection patients had significantly
      less pain (visual analog scale) at 3-month follow-up and more flexion at 6-month
      follow-up. Tenderness, pain on motion, and crepitus were significantly more
      likely to be absent from injection patients at the 3- and 6-month follow-ups.
      Patients with osteoarthritis and a symptomatic meniscus tear may experience more
      pain relief and functional mobility after arthroscopic surgery plus hyaluronic
      acid injections than after arthroscopy alone.

PMID- 20145787
TI  - Reproducibility of radiographic measurements in assessment of congenital talipes
      equinovarus.
AB  - Six commonly measured parameters in the assessment of congenital clubfoot were
      retrospectively assessed from standardized preoperative and intraoperative
      radiographs taken during operative complete subtalar release. These radiographic
      parameters were measured in 30 feet by 6 observers at 2 separate readings. The
      observers were orthopedic residents in different stages of training. Between
      observers intraclass correlation coefficients (ICCs) were computed for each
      parameter. All radiographic parameters were found to be reproducible across time
      and observers (range of preoperative intraobserver ICCs, 0.84-0.99; range of
      preoperative interobserver ICCs, 0.93-0.99), except for intraoperative
      anteroposterior (AP) talar-first metatarsal angle (intraoperative intraobserver
      ICC, 0.79) and lateral talocalcaneal angle (intraoperative interobserver ICC,
      0.81). Differences in mean preoperative measurements between observers and time
      were tested by analysis of variance. There were no significant differences
      between observers and time in the 6 preoperative measurements (P<.05), except for
      intraoperative AP talar-first metatarsal angle, AP talocalcaneal angle, and
      degree of AP calcaneocuboid subluxation, which were significantly different
      (P<.05). Our results support use of radiographs as a reliable method for guiding
      care in patients with clubfoot and as a reproducible method that physicians can
      use for comparisons.

PMID- 20145788
TI  - Tibial plateau fracture with proximal tibia autograft harvest for foot surgery.

PMID- 20145789
TI  - Arthroscopic rotator cuff repair failure resulting from decortication of the
      rotator cuff footprint: a case report.

PMID- 20145790
TI  - Endobutton-assisted repair of complete distal biceps tendon rupture in a woman.

PMID- 20145791
TI  - Are you Red Flag ready?

PMID- 20145792
TI  - Reverse passage of the suture lasso in arthroscopic rotator cuff repair.
AB  - Suture passage in arthroscopic rotator cuff repair can be technically difficult.
      The suture lasso is typically passed antegrade from the bursal side of the
      rotator cuff. Antegrade passage of the suture lasso can be particularly difficult
      when visualization is limited. Reverse passage of the suture lasso from the
      undersurface can be used to place sutures in technically challenging
      circumstances. The suture lasso is placed retrograde through the undersurface of
      the rotator cuff and used as a suture shuttle to bring sutures back through the
      rotator cuff. This technique is easily reproducible and cost-effective, and it
      requires only 2 working arthroscopy portals.

PMID- 20145793
TI  - Imaging series. Pigmented villonodular synovitis.

PMID- 20145795
TI  - Pantaloon hip spica cast and constrained liner for the treatment of early total
      hip dislocation in a young patient with sickle cell disease.

PMID- 20145794
TI  - Hemostasis using a bipolar sealer in primary unilateral total knee arthroplasty.
AB  - Previous studies have shown that, compared with standard electrocautery, a
      bipolar sealer reduces tissue damage and smoke production during surgery. We
      conducted a multicenter, prospective, randomized study to compare a bipolar
      sealer with standard electrocautery for hemostasis. Sixty-nine primary total knee
      arthroplasties were performed. Cohorts were evaluated for intraoperative and
      postoperative blood loss, blood transfusion requirements, postoperative
      hemoglobin and pain levels, length of hospital stay, range of motion, and Knee
      Society scores. Amount of blood loss and decrease in postoperative hemoglobin
      were significantly lower in the bipolar sealer group than in the standard
      electrocautery group. Need for autologous blood transfusions was decreased in the
      bipolar sealer group compared with the electrocautery group. There were no
      between-groups differences in clinical knee scores. The bipolar sealer was an
      effective coagulation alternative for total knee arthroplasties in reducing blood
      loss and transfusion requirements without affecting clinical outcome.

PMID- 20145796
TI  - Diffuse pigmented villonodular synovitis of the ankle with severe bony
      destruction: treatment of a case by surgical excision with limited arthrodesis.

PMID- 20145799
TI  - Nucleic acid simulations themed issue.

PMID- 20145800
TI  - Simulation of DNA catenanes.
AB  - DNA catenanes are important objects in biology, foremost as they appear during
      replication of circular DNA molecules. In this review we analyze how
      conformational properties of DNA catenanes can be studied by computer simulation.
      We consider classification of catenanes, their topological invariants and the
      methods of calculation of these invariants. We briefly analyze the DNA model and
      the simulation procedure used to sample the equilibrium conformational ensemble
      of catenanes with a particular topology. We consider how to avoid direct
      simulation of many DNA molecules when we need to account for the linking
      unlinking process. The simulation methods and their comparisons with experiments
      are illustrated by some examples. We also describe an approach that allows
      simulating the steady state fraction of DNA catenanes created by type II
      topoisomerases.

PMID- 20145801
TI  - Viral assembly: a molecular modeling perspective.
AB  - Icosahedral viruses are among the smallest and simplest of biological systems.
      The investigation of their structures represented the first step toward the
      establishment of molecular biophysics, over half a century ago. Many research
      groups are now pursuing investigations of viral assembly, a process that could
      offer new opportunities for the design of antiviral drugs and novel
      nanoparticles. A variety of experimental, theoretical and computational methods
      have been brought to bear on the study of virus structure and assembly. In this
      Perspective we review the contributions of theoretical and computational
      approaches to our understanding of the structure, energetics, thermodynamics and
      assembly of DNA bacteriophage and single-stranded icosahedral RNA viruses.

PMID- 20145802
TI  - On the parameterization of rigid base and basepair models of DNA from molecular
      dynamics simulations.
AB  - A method is described to extract a complete set of sequence-dependent material
      parameters for rigid base and basepair models of DNA in solution from atomistic
      molecular dynamics simulations. The method is properly consistent with
      equilibrium statistical mechanics, leads to effective shape, stiffness and mass
      parameters, and employs special procedures for treating spontaneous torsion angle
      flips and H-bond breaks, both of which can have a significant effect on the
      results. The method is accompanied by various analytical consistency checks that
      can be used to assess the equilibration of statistical averages, and different
      modeling assumptions pertaining to the rigidity of the bases and basepairs and
      the locality of the quadratic internal energy. The practicability of the approach
      is verified by estimating complete parameter sets for the 16-basepair palindromic
      oligomer G(TA)(7)C simulated in explicit water and counterions. Our results
      indicate that the method is capable of resolving sequence-dependent variations in
      each of the material parameters. Moreover, they show that the assumptions of
      rigidity and locality hold rather well for the base model, but not for the
      basepair model. For the latter, it is shown that the non-local nature of the
      internal energy can be understood in terms of a certain compatibility relation
      involving Schur complements.

PMID- 20145803
TI  - Simulation of DNA double-strand dissociation and formation during replica
      exchange molecular dynamics simulations.
AB  - The process of DNA double-strand (dsDNA) formation for a four-base pair
      (dCGCG)(2) model system was studied using umbrella sampling combined with replica
      exchange molecular dynamics simulations (REMD) and a generalized Born continuum
      solvent model. Disruption of dsDNA during the simulations was achieved by
      stepwise increasing the reference distance in a quadratic restraining potential
      between the nucleic acid backbone of the two DNA strands. During the reverse
      simulation (stepwise decrease of the distance starting from completely separated
      and unfolded single strands) full reformation of a dsDNA in close agreement with
      B-form geometry was achieved during REMD but not continuous MD simulations. The
      simulations allowed the calculation of a potential of mean force for the dsDNA
      formation along the reaction coordinate and were used to characterize
      intermediate structures. In addition, it was possible to analyze the change of
      various energetic contributions during disruption and formation of dsDNA that
      favor or disfavor duplex formation. The calculated free energy change of
      approximately -3.2 (+/-1.5) kcal mol(-1) and enthalpy change of approximately -37
      kcal mol(-1) for (dCGCG)(2) duplex formation was in good agreement with
      corresponding experimental values of approximately -3.9 kcal mol(-1) and -38.5
      kcal mol(-1), respectively.

PMID- 20145804
TI  - The impact of monovalent ion force field model in nucleic acids simulations.
AB  - Different classical models for monovalent ions (typically used to neutralize
      proteins or nucleic acids) are available in the literature and are widely used in
      molecular dynamics simulations without a great knowledge of their quality,
      consistency with the macromolecular force field and impact on the global
      simulation results. In this paper the ability of several of the most popular ion
      models to reproduce both quantum mechanics and experimental results is examined.
      Artefacts due to the use of incorrect ion models in molecular dynamics
      simulations of concentrated solutions of NaCl and KCl in water and of a short DNA
      duplex in 500 mM aqueous solutions of NaCl and KCl have been analyzed. Our
      results allow us to discuss the robustness and reliability of different ion
      models and to highlight the source of potential errors arising from non-optimal
      models. However, it is also found that the structural and dynamic characteristics
      of DNA (as an example of a heavily charged macromolecule) in near-physiological
      conditions are quite independent of the ion model used, providing support to most
      already-published simulations of macromolecules.

PMID- 20145805
TI  - Stabilization of radical anion states of nucleobases in DNA.
AB  - Trapping of an electron by DNA leads to the formation of radical anion states of
      pyrimidine bases. Because these states play an important role in biological and
      chemical processes, their computational treatment is of particular interest. We
      show that simple electrostatic and quantum chemical models can accurately
      reproduce the adiabatic electron affinities (EAs) of short DNA stacks recently
      derived from high-level ab initio calculations (M. Kobylecka, J. Leszczynski, and
      J. Rak, J. Am. Chem. Soc., 2008, 130, 15683). The electrostatic interaction of an
      excess electron localized on cytosine or thymine with intra- and inter-strand
      adjacent nucleobases is found to strongly affect the energy of the radical
      anions. This interaction is the main origin of the dependence of EA of
      nucleobases on the nature of neighboring base pairs. In particular, the states
      XT(-)Y and XC(-)Y, where X and Y = C, T, are, by ca. 0.7 eV, more stable than
      radical anions GT(-)G and GC(-)G. We find that second-neighbor effects can also
      significantly modulate EAs, although being smaller than the effects of adjacent
      bases. The strongest destabilizing effect is found for 5'-GC and 3'-GC, while the
      5'-AT base pair stabilizes the radical anion states. Using a combined QM/MD
      approach, we consider how structural fluctuations of DNA influence the stability
      of the radical anion states. Despite large dispersions of the stabilization
      energies due to conformational dynamics of DNA, there are only few thermally
      accessible structures where GT(-)G and GC(-)G are energetically more favorable
      than the corresponding pyrimidine triplets. Although stabilization energies
      calculated for stacks of regular structure are in qualitative agreement with the
      QM/MD results, structural fluctuations of pi stacks should be taken into account
      for more accurate description of the excess electron trapped by DNA. The results
      obtained in this study suggest that simple electrostatic models, in combination
      with MD simulations, can be very helpful to explore the long time scale behavior
      of radical anions in DNA.

PMID- 20145806
TI  - Charge transfer equilibria of aqueous single stranded DNA.
AB  - The charge transfer thermodynamics of a simple model of DNA, a single stranded 10
      mer poly-adenine oligonucleotide, in water is investigated by means of a
      computational/theoretical procedure, in which all the relevant environmental
      effects are considered. Our data indicate that water and counterions ultimately
      dominate the DNA reduction and oxidation free energies, which are also strongly
      influenced by the base position along the strand. In fact, we estimated that
      reduction free energies are large and negative, particularly for the bases close
      to the 5' and 3' positions, whereas the electron detachment is thermodynamically
      unfavoured all along the strand, but with a higher free energy cost in the
      central region of the molecule. Further investigation on double charging, i.e.
      one nucleobase is oxidized and one is reduced within the strand, predicts that
      charge-separated states are possible and thermodynamically largely stable when
      the ionic forms are separated by several nucleobases.

PMID- 20145807
TI  - Structural ultrafast dynamics of macromolecules: diffraction of free DNA and
      effect of hydration.
AB  - Of special interest in molecular biology is the study of structural and
      conformational changes which are free of the additional effects of the
      environment. In the present contribution, we report on the ultrafast unfolding
      dynamics of a large DNA macromolecular ensemble in vacuo for a number of
      temperature jumps, and make a comparison with the unfolding dynamics of the DNA
      in aqueous solution. A number of coarse-graining approaches, such as kinetic
      intermediate structure (KIS) model and ensemble-averaged radial distribution
      functions, are used to account for the transitional dynamics of the DNA without
      sacrificing the structural resolution. The studied ensembles of DNA
      macromolecules were generated using distributed molecular dynamics (MD)
      simulations, and the ensemble convergence was ensured by monitoring the ensemble
      averaged radial distribution functions and KIS unfolding trajectories. Because
      the order-disorder transition in free DNA implies unzipping, coiling, and strand
      separation processes which occur consecutively or competitively depending on the
      initial and final temperature of the ensemble, DNA order-disorder transition in
      vacuo cannot be described as a two-state (un)folding process.

PMID- 20145808
TI  - Relaxation dynamics of nucleosomal DNA.
AB  - Recent experimental and theoretical evidence demonstrates that proteins and water
      in the hydration layer can follow complex stretched exponential or power law
      relaxation dynamics. Here, we report on a 50 ns all atom molecular dynamics (MD)
      simulation of the yeast nucleosome, where the interactions between DNA, histones,
      surrounding water and ions are explicitly included. DNA interacts with the
      histone core in 14 locations, approximately every 10.4 base pairs. We demonstrate
      that all sites of interaction exhibit anomalously slow power law relaxation,
      extending up to 10 ns, while fast exponential relaxation dynamics of hundreds of
      picoseconds applies to DNA regions outside these locations. The appearance of
      1/f(alpha) noise or pink noise in DNA dynamics is ubiquitous. For histone-bound
      nucleotide dynamics alpha --> 1 and is a signature of complexity of the protein
      DNA interactions. For control purposes two additional DNA simulations free of
      protein are conducted. Both utilize the same sequence of DNA, as found the in the
      nucleosome. In one simulation the initial conformation of the double helix is a
      straight B-form. In the other, the initial conformation is super helical. Neither
      of these simulations exhibits the variation of alpha as a function of position,
      the measure of power law for dynamical behavior, which we observe in the
      nucleosome simulation. The unique correspondence (high alpha to DNA-histone
      interaction sites, low alpha to free DNA sites), suggests that alpha may be an
      important and new quantification of protein-DNA interactions for future
      experiments.

PMID- 20145809
TI  - Sensors for DNA detection: theoretical investigation of the conformational
      properties of immobilized single-strand DNA.
AB  - A major challenge in the design and creation of biomolecular sensors is the
      development of efficient strategies using both existing synthetic technologies
      and novel fabrication methods to effectively adsorb and assemble different
      molecular species on suitable substrates. In order to generate stable and
      effective biodevices it is fundamental to understand the mechanisms responsible
      for the formation of the supramolecular structures, to evaluate to what extent
      the function and conformation of the adsorbed macromolecules are influenced by
      their interactions with the substrates and the environment and to identify
      possible causes of disruption, with the ultimate aim of suggesting and selecting
      appropriate methodologies to design highly efficient systems. Here in silico
      modeling comes into play, provided that realistic models and reliable
      computational strategies are employed. This paper is focused on DNA detection
      systems based on the hybridization between a DNA target and its complementary
      probe, which is present either in solution or on a solid support. MD simulations
      of the fully hydrated single strand attached to an allylamine functionalized
      Si(111) surface in aqueous solution are presented. A reliable and high quality
      picture of the structural flexibility and dynamic properties of the modified and
      unmodified DNA segment in solution together with the ability of DNA to rearrange
      its structure due to environmental effects is given and clarified.

PMID- 20145811
TI  - Dynamics of a fluorophore attached to superhelical DNA: FCS experiments simulated
      by Brownian dynamics.
AB  - We investigated the dynamics of a single-fluorophore-labeled pUC18 plasmid
      through a Brownian dynamics algorithm, followed by a simulation of the
      fluorescence correlation spectroscopy (FCS) process. Recent experimental FCS
      measurements indicated a sensitivity of the monomer mean square displacements in
      DNA circles towards superhelicity. Simulations with homogeneous DNA elasticity
      and local straight equilibrium are not sufficient to reproduce this observed
      behavior. But inserting permanently bent sequences into the DNA, which favor end
      loop formation, caused a dependence of the calculated FCS correlation curves on
      superhelical density. Furthermore, our simulations allow us to take into account
      the orientation of the fluorophore in polarized excitation, which might explain
      the observed appearance of a Rouse-like regime at intermediate time scales.

PMID- 20145810
TI  - Effects of the biological backbone on DNA-protein stacking interactions.
AB  - The pi-pi stacking (face-to-face) interactions between the five natural DNA or
      RNA nucleobases and the four aromatic amino acids were compared using three
      different types of dimers: (1) a truncated nucleoside (nucleobase) stacked with a
      truncated amino acid; (2) a truncated nucleoside (nucleobase) stacked with an
      extended amino acid; and (3) a nucleoside (extended nucleobase) stacked with a
      truncated amino acid. Systematic (MP2/6-31G*(0.25)) potential energy surface
      scans reveal important information about the effects of the deoxyribose sugar and
      protein backbone on the structure and binding energy between truncated nucleobase
      and amino acid models that are typically implemented in the literature. Most
      notably, electrostatic and steric interactions arising from the bulkiness of the
      biological backbones can change the preferred relative orientations of DNA and
      protein pi-systems. More importantly, the protein backbone can strengthen the
      stacking energy (by up to 10 kJ mol(-1)), while the deoxyribose moiety can
      strengthen or weaken the stacking interaction depending on the positioning of the
      amino acid relative to the sugar residue. These effects are likely due to
      additional interactions between the amino acid or nucleobase ring and the
      backbone in the extended monomer rather than significant changes in the
      properties of the biological pi-systems upon model extension. Since the present
      work reveals that all calculated DNA-protein stacking interactions are
      significant and approach the strength of other noncovalent interactions between
      biomolecules, both pi-pi and backbone-pi interactions must be considered when
      attempting to gain a complete picture of DNA-protein binding.

PMID- 20145812
TI  - A detailed binding free energy study of 2:1 ligand-DNA complex formation by
      experiment and simulation.
AB  - In 2004, we used NMR to solve the structure of the minor groove binder
      thiazotropsin A bound in a 2:1 complex to the DNA duplex, d(CGACTAGTCG)2. In this
      current work, we have combined theory and experiment to confirm the binding
      thermodynamics of this system. Molecular dynamics simulations that use
      polarizable or non-polarizable force fields with single and separate trajectory
      approaches have been used to explore complexation at the molecular level. We have
      shown that the binding process invokes large conformational changes in both the
      receptor and ligand, which is reflected by large adaptation energies. This is
      compensated for by the net binding free energy, which is enthalpy driven and
      entropically opposed. Such a conformational change upon binding directly impacts
      on how the process must be simulated in order to yield accurate results. Our MM
      PBSA binding calculations from snapshots obtained from MD simulations of the
      polarizable force field using separate trajectories yield an absolute binding
      free energy (-15.4 kcal mol(-1)) very close to that determined by isothermal
      titration calorimetry (-10.2 kcal mol(-1)). Analysis of the major energy
      components reveals that favorable non-bonded van der Waals and electrostatic
      interactions contribute predominantly to the enthalpy term, whilst the
      unfavorable entropy appears to be driven by stabilization of the complex and the
      associated loss of conformational freedom. Our results have led to a deeper
      understanding of the nature of side-by-side minor groove ligand binding, which
      has significant implications for structure-based ligand development.

PMID- 20145813
TI  - Molecular simulation of conformational transitions in biomolecules using a
      combination of structure-based potential and empirical valence bond theory.
AB  - The functions of biological macromolecules are inherently linked to their complex
      conformational behaviour. As a consequence of this complexity, the corresponding
      potential energy landscapes encompass multiple minima. Some of the intermediate
      structures between initial and final states can be characterized by experimental
      techniques. Computer simulations can explore the dynamics of individual states
      and bring these together to rationalize the overall process. Here, we show that
      the experimental structures can be exploited to define simple yet accurate
      atomistic structure-based potentials (SBP) that describe individual
      conformational states. These individual states can then be coupled by using the
      empirical valence bond (EVB) model. The overall energy landscape can easily be
      parameterised to reproduce available kinetic and thermodynamic data. We
      illustrate the procedure by applying the EVB-SBP method to study base flipping in
      B-DNA. Simple SBP is shown to reproduce structural ensembles obtained by using
      more refined force field simulations. Umbrella sampling in conjunction with the
      general energy gap reaction coordinate enables us to study alternative molecular
      pathways efficiently. We find that base rotation takes place via both grooves of
      the B-DNA with a marked preference for the major groove pathway. We also identify
      an unusual high-energy off-pathway intermediate that may appear if the base
      closing process is initiated from a syn base.

PMID- 20145814
TI  - Dependence of A-RNA simulations on the choice of the force field and salt
      strength.
AB  - We present an extensive molecular dynamics study (0.6 micros in total) on three A
      RNA duplexes. The dependence of the A-RNA geometry on force fields (Parm99 and
      Parmbsc0) and salt strength conditions (approximately 0.18 M net-neutralizing
      Na(+) and approximately 0.3 M KCl) was investigated. The Parmbsc0 force field
      makes the A-RNA duplex more compact in comparison to the Parm99 by preventing
      temporary alpha/gamma t/t flips common in Parm99 simulations. Nevertheless, since
      the alpha/gamma t/t sub-state occurs to certain extent in experimental A-RNA
      structures, we consider both force fields as viable. The stabilization of the A
      RNA helices caused by the Parmbsc0 force field includes visible reduction of the
      major groove width, increase of the base pair roll, larger helical inclination
      and small increases of twist. Therefore, the Parmbsc0 shifts the simulated
      duplexes more deeply into the A-form. Further narrowing of the deep major groove
      is observed in excess salt simulations, again accompanied by larger roll,
      inclination and twist. The cumulative difference between Parm99/lower-salt and
      Parmbsc0/higher-salt simulations is approximately 4-8 A for the average PP
      distances, and -0.7 to -2.5 degrees, -2.0 to -5.4 degrees, -2.6 to -8.6 degrees
      and 1.7 to 7.0 degrees for the twist, roll, inclination and propeller,
      respectively. The effects of the force field and salt condition are sequence
      dependent. Thus, the compactness of A-RNA is sensitive to the sequence and the
      salt strength which may, for example, modulate the end-to-end distance of the A
      RNA helix. The simulations neatly reproduce the known base pair roll re
      distribution in alternating purine-pyrimidine A-RNA helices.

PMID- 20145815
TI  - Protein-DNA binding specificity: a grid-enabled computational approach applied to
      single and multiple protein assemblies.
AB  - We use a physics-based approach termed ADAPT to analyse the sequence-specific
      interactions of three proteins which bind to DNA on the side of the minor groove.
      The analysis is able to estimate the binding energy for all potential sequences,
      overcoming the combinatorial problem via a divide-and-conquer approach which
      breaks the protein-DNA interface down into a series of overlapping oligomeric
      fragments. All possible base sequences are studied for each fragment. Energy
      minimisation with an all-atom representation and a conventional force field
      allows for conformational adaptation of the DNA and of the protein side chains
      for each new sequence. As a result, the analysis depends linearly on the length
      of the binding site and complexes as large as the nucleosome can be treated,
      although this requires access to grid computing facilities. The results on the
      three complexes studied are in good agreement with experiment. Although they all
      involve significant DNA deformation, it is found that this does not necessarily
      imply that the recognition will be dominated by the sequence-dependent mechanical
      properties of DNA.

PMID- 20145816
TI  - Evaluation of molecular modelling methods to predict the sequence-selectivity of
      DNA minor groove binding ligands.
AB  - The accurate prediction of ligand-receptor interaction energies by molecular
      modelling methods remains challenging. Predicting and understanding the sequence
      selectivity of DNA minor groove-binding ligands constitutes a particularly
      interesting and potentially valuable aspect of this. Here, we use experimental
      data on the binding of Hoechst 33258 to the minor groove of various A/T-rich DNA
      duplexes to evaluate the reliability of a popular class of molecular modelling
      methods based on the energetic analysis of molecular dynamics (MD) simulations.
      We examine how performance depends on the use of explicit versus implicit solvent
      models, on the use of generalised Born versus Poisson-Boltzmann models to
      evaluate solvent-associated energetic terms, and the use of normal mode analysis
      to evaluate entropic factors. Quantitatively evaluating many different
      combinations of methodologies, we find that the most reliable results are
      obtained when the MD simulations are performed in explicit solvent, when the data
      is processed using the MM-PB/SA approach, and when normal mode analysis is used
      to estimate configurational entropy changes.

PMID- 20145828
TI  - Physical chemistry of ionic liquids.

PMID- 20145817
TI  - Mesoscale simulations of two nucleosome-repeat length oligonucleosomes.
AB  - The compaction of chromatin, accessed through coarse-grained modeling and
      simulation, reveals different folding patterns as a function of the nucleosome
      repeat length (NRL), the presence of the linker histone, and the ionic strength.
      Our results indicate that the linker histone has negligible influence on short
      NRL fibers, whereas for longer NRL fibers it works like, and in tandem with,
      concentrated positive counterions to condense the chromatin fiber. Longer NRL
      fibers also exhibit structural heterogeneity, with solenoid-like conformations
      viable in addition to irregular zigzags. These features of chromatin and
      associated internucleosomal patterns presented here help interpret structural
      dependencies of the chromatin fiber on internal and external factors. In
      particular, we suggest that longer-NRL are more advantageous for packing and
      achieving various levels of fiber compaction throughout the cell cycle.

PMID- 20145829
TI  - Ionicity in ionic liquids: correlation with ionic structure and physicochemical
      properties.
AB  - Ionic liquids (ILs) are ambient temperature molten salts that have attracted
      considerable attention because of their negligible volatility, thermal stability,
      nonflammability, and high ionic conductivity. These remarkable properties result
      essentially from their ionic nature. Thus, the concept of ionicity of ILs (i.e.
      how ionic they are) is of great significance for characterising their properties.
      Here, we show the methodologies used to assess the ionic nature in ILs. On the
      basis of quantitative estimation of the ionicity, their dependence on ionic
      structure, polarity scales, and physicochemical properties is reviewed. The
      ionicity of certain ILs is also predicted from their physicochemical properties.
      The effects of different classes of ILs (e.g., protic ILs and lithium ILs) and
      binary systems consisting of ILs and other components on the ionicity are also
      discussed.

PMID- 20145830
TI  - Ionic liquids and reactions at the electrochemical interface.
AB  - Ionic liquids (ILs) represent a fascinating, and yet to be fully understood,
      medium for a variety of chemical, physical and biological processes.
      Electrochemical processes form an important subset of these that are particularly
      of interest, since ILs tend to be good electrochemical solvents and exhibit other
      properties which make them very useful as electrolytes in electrochemical
      devices. It is important therefore to understand the extent to which
      electrochemical reactions and processes behave in a relatively "normal", for
      example aqueous solution, fashion as opposed to exhibiting phenomena more
      uniquely the product of their organic ionic nature. This perspective examines a
      range of electrochemical reactions in ionic liquids, in many cases in the context
      of real world applications, to highlight the phenomena as far as they are
      understood and where data gaps exist. The important areas of lithium and
      conducting polymer electrochemistry are discussed in detail.

PMID- 20145831
TI  - Accelerating the discovery of biocompatible ionic liquids.
AB  - High throughput screening is the first stage of determining the ecotoxicity of
      ionic liquids. The available methods are reviewed, and a critical analysis of the
      problems and pitfalls is presented.

PMID- 20145832
TI  - Design of functional ionic liquids using magneto- and luminescent-active anions.
AB  - Some recent developments concerning the syntheses and physical properties of
      functional ionic liquids, especially those having paramagnetic and luminescent
      properties, are highlighted. The component ions used so far include both
      inorganic and organic types; and various strategies, namely not only the proper
      choice but also the synthesis of anions to impart the functionality, are
      presented.

PMID- 20145833
TI  - Ionic liquids in surface electrochemistry.
AB  - Ionic liquids (IL) are widely used in electrochemistry due to their excellent
      properties such as good ionic conductivity, wide electrochemical potential
      window, high viscosity, high thermal stability, wide liquid range and tunable
      solvent properties. In electrochemistry, the performance of an electrochemical
      system is dependent on the properties of the interface at the IL/electrode. This
      review presents the surface electrochemistry in ILs, and the interfacial
      structures of IL/electrode and heterogeneous electron-transfer kinetics are
      detailed. Finally, the updated researches on the electrochemical applications of
      ILs such as electrode deposition, electrosynthesis, electrocatalysis,
      electrochemical biosensing, electrochemical capacitor and lithium batteries are
      demonstrated.

PMID- 20145834
TI  - Photochemical processes in ionic liquids on ultrafast timescales.
AB  - The number of investigations of room temperature ionic liquids (RTILs) has been
      developing rapidly in recent years, e.g., due to their potential use as "green
      solvents" in many industrial applications. A large body of data has been
      accumulated on physico-chemical properties including ultrafast dynamics of these
      liquids. This review deals both with the generation and the subsequent relaxation
      dynamics of selected transient species following photolysis or pulse radiolysis
      of RTILs with special emphasis on the exceptional character of imidazolium based
      systems. Although considerable progress has been made, the understanding of the
      photochemistry of ionic liquids is just at its embryonic stage. Nevertheless, a
      brief comparison with high temperature ionic liquids (HTILs) such as alkali metal
      doped alkali halide mixtures already reveals important differences.

PMID- 20145835
TI  - At the interface: solvation and designing ionic liquids.
AB  - Ionic liquids' (ILs) remarkable and tunable physicochemical properties mean they
      have distinct performance advantages over conventional solvents in many settings.
      However, the use of ILs in surface-dependent processes (e.g. electrodeposition,
      heterogeneous catalysis, dye solar cells) is hindered by the lack of a systematic
      understanding of IL interfacial structure. In this Perspective, we highlight
      recent experiments which show interfacial IL nanostructure is a consequence of
      both surface-specific and bulk liquid interactions. These results enable us to
      develop molecular design rules for controlling interfacial IL behavior.

PMID- 20145836
TI  - Do solvation layers of ionic liquids influence electrochemical reactions?
AB  - In this discussion paper we discuss our recent results on the electrodeposition
      of materials and in situ STM/AFM measurements which demonstrate that ionic
      liquids should not be regarded as neutral solvents which all have similar
      properties. In particular, we focus on differences in interfacial structure
      (solvation layers) on metal electrodes as a function of ionic liquid species.
      Recent theoretical and experimental results show that conventional double layers
      do not form on metal electrodes in ionic liquid systems. Rather, a multilayer
      architecture is present, with the number of layers determined by the ionic liquid
      species and the properties of the surface; up to seven discrete interfacial
      solvent layers are present on electrode surfaces, consequently there is no simple
      electrochemical double layer. Both the electrodeposition of aluminium and of
      tantalum are strongly influenced by ionic liquids: in 1-butyl-1
      methylpyrrolidinium bis(trifluoromethylsulfonyl)amide, [Py(1,4)]TFSA, aluminium
      is obtained as a nanomaterial, whereas in 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)amide, [EMIm]TFSA, a microcrystalline material is
      made. Tantalum can be deposited from [Py(1,4)]TFSA, whereas from [EMIm]TFSA only
      non-stoichiometric tantalum fluorides TaF(x) are obtained. It is likely that
      solvation layers influence these reactions.

PMID- 20145837
TI  - Screening of pairs of ions dissolved in ionic liquids.
AB  - The properties of pairs of solute ions in the ionic liquid, dimethylimidazolium
      chloride or [dmim][Cl], are studied as a function of their separation. The
      potential of mean force curves show that there is only a small stabilisation of
      ion pairs with opposite charges followed by a barrier to separation. Ion pairs
      with the same charge are also stabilised by solvent screening due to induced
      polarisation of the solvent. In both cases screening is essentially complete
      outside the first shell, but is large even when there is no solvent between the
      ions. Charge distributions in the solvation shells around ion pairs are shown and
      the results interpreted with the aid of a simple model of two ions in an
      spheroidal cavity in a conducting medium. The actual or Madelung potential
      experienced by the second solute ion is found to decay rapidly with distance and
      does not show the oscillations found in the Poisson potential around a single
      solute ion. We conclude that ionic liquids provide very effective electrostatic
      screening between solute molecules.

PMID- 20145838
TI  - Spontaneous product segregation from reactions in ionic liquids: application in
      Pd-catalyzed aliphatic alcohol oxidation.
AB  - A methodology is introduced to separate polar reaction products from ionic
      liquids without the need for organic solvent extraction or distillation. We
      investigated product isolation after an alcohol oxidation performed in ionic
      liquids. Suitable ionic liquids were selected based on their mixing or demixing
      with a range of alcohols and the derived ketones. The aim was to obtain complete
      miscibility with the alcohol substrate at reaction temperature and a clear phase
      separation of the derived ketone product at room temperature. Six imidazolium
      based ionic liquids displayed this desired behaviour and were sufficiently stable
      to oxidation. These ionic liquids were then employed in the oxidation of non
      activated aliphatic alcohols with molecular oxygen in the presence of
      palladium(II) acetate. In 1-butyl-3-methylimidazolium tetrafluoroborate, 2-ketone
      yields of 79 and 86% were obtained for, respectively, 2-octanol and 2-decanol.
      After cooling to room temperature the ionic liquid expels the immiscible ketone
      and the product phase can be isolated by decantation. In addition, the ionic
      liquid acts as an immobilization medium for the palladium catalyst, allowing
      efficient catalyst recycling.

PMID- 20145839
TI  - Plasma electrochemistry in ionic liquids: deposition of copper nanoparticles.
AB  - We report on the synthesis of copper nanoparticles in two different water- and
      air-stable ionic liquids using plasma electrochemical deposition. The copper
      nanoparticles were deposited in 1-butyl-1-methylpyrrolidinium
      bis(trifluoromethylsulfonyl)amide ([Py(1,4)]Tf(2)N) and 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)amide ([EMIm]Tf(2)N). To get
      information on the dimensions of the particles made, we have applied in situ
      transmission electron microscopy (TEM) (particles in ionic liquid). The chemical
      composition was investigated by ex situ X-ray photoelectron spectroscopy (XPS).
      We found that the copper particles produced in [Py(1,4)]Tf(2)N were larger in
      size compared to the particles obtained in [EMIm] Tf(2)N (roughly 20 vs. 10 nm).
      The chemical composition of the particle surface differs too. In both cases the
      particles are partly oxidised leading to a CuO shell, but the particles obtained
      in [Py(1,4)]Tf(2)N carry a lot of residues from the ionic liquid.

PMID- 20145840
TI  - Patterns of protein unfolding and protein aggregation in ionic liquids.
AB  - The objective of this study is to characterize the effect of ionic liquids (ILs)
      on the stability of proteins with regard to denaturation, protein aggregation and
      the formation of folding intermediates. Ribonuclease A was used as a model
      protein. A variety of ILs were tested. Detailed results are reported for choline
      dihydrogenphosphate, which enhances the thermal stability of the native state,
      and 1-ethyl-3-methylimidazolium dicyanamide, which acts as a strong denaturant.
      Varied factors include the intrinsic properties of the samples such as the IL
      concentration and the pH value as well as external factors such as incubation
      conditions. The time course of the deactivation processes was monitored. ILs can
      be used to suppress protein aggregation and steer the formation of intermediates.

PMID- 20145841
TI  - Thermo-solvatochromism in binary mixtures of water and ionic liquids: on the
      relative importance of solvophobic interactions.
AB  - The thermo-solvatochromism of 2,6-dibromo-4-[(E)-2-(1-methylpyridinium-4
      yl)ethenyl] phenolate, MePMBr(2), has been studied in mixtures of water, W, with
      ionic liquids, ILs, in the temperature range of 10 to 60 degrees C, where
      feasible. The objectives of the study were to test the applicability of a
      recently introduced solvation model, and to assess the relative importance of
      solute-solvent solvophobic interactions. The ILs were 1-allyl-3-alkylimidazolium
      chlorides, where the alkyl groups are methyl, 1-butyl, and 1-hexyl, respectively.
      The equilibrium constants for the interaction of W and the ILs were calculated
      from density data; they were found to be linearly dependent on N(C), the number
      of carbon atoms of the alkyl group; van't Hoff equation (log K versus 1/T)
      applied satisfactorily. Plots of the empirical solvent polarities, E(T)
      (MePMBr(2)) in kcal mol(-1), versus the mole fraction of water in the binary
      mixture, chi(w), showed non-linear, i.e., non-ideal behavior. The dependence of
      E(T) (MePMBr(2)) on chi(w), has been conveniently quantified in terms of
      solvation by W, IL, and the "complex" solvent IL-W. The non-ideal behavior is due
      to preferential solvation by the IL and, more efficiently, by IL-W. The deviation
      from linearity increases as a function of increasing N(C) of the IL, and is
      stronger than that observed for solvation of MePMBr(2) by aqueous 1-propanol, a
      solvent whose lipophilicity is 12.8 to 52.1 times larger than those of the ILs
      investigated. The dependence on N(C) is attributed to solute-solvent solvophobic
      interactions, whose relative contribution to solvation are presumably greater
      than that in mixtures of water and 1-propanol.

PMID- 20145842
TI  - High vacuum distillation of ionic liquids and separation of ionic liquid
      mixtures.
AB  - The vaporisation of ionic liquids has been investigated using temperature
      programmed desorption (TPD) and ultra-high vacuum (UHV) distillation. 1-Alkyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquids,
      [C(n)C(1)Im][Tf(2)N] (n = 2, 8), have been distilled at UHV and T > 500 K in a
      specially designed still. The distillation process yielded spectroscopically pure
      ionic liquid distillates with complete removal of volatile impurities such as
      water, argon and 1-methylimidazole. Such UHV distillation offers a method of
      obtaining high purity ionic liquids for analytical applications. The vapour phase
      of the ionic liquid mixtures [C(2)C(1)Im](0.05)[C(8)C(1)Im](0.95)[Tf(2)N] and
      [C(2)C(1)Im][C(8)C(1)Im][Tf(2)N][EtSO(4)] has been analysed by TPD using line-of
      sight mass spectrometry (LOSMS). The vapour phase consisted of all possible
      combinations of neutral ion pairs (NIPs) from the liquid mixture. Neither mixture
      showed evidence of decomposition during TPD, and the
      [C(2)C(1)Im](0.05)[C(8)C(1)Im](0.95)[Tf(2)N] mixture was shown to obey Raoult's
      law. Based on the TPD results, fractional distillations were attempted for
      [C(2)C(1)Im][C(8)C(1)Im][Tf(2)N](2) and [C(2)C(1)Im][C(8)C(1)Im][Tf(2)N][EtSO(4)]
      mixtures. The distillate from [C(2)C(1)Im][C(8)C(1)Im][Tf(2)N](2) was enhanced in
      the more volatile [C(2)C(1)Im][Tf(2)N] components, but the
      [C(2)C(1)Im][C(8)C(1)Im][Tf(2)N][EtSO(4)] mixture underwent significant
      decomposition. The similarities and differences between UHV TPD, and high vacuum
      distillation, of ionic liquids, are discussed. Design parameters are outlined for
      a high vacuum ionic liquid still that will minimise decomposition and maximise
      separation of ILs of differing volatility.

PMID- 20145843
TI  - Blending ionic liquids: how physico-chemical properties change.
AB  - Ionic liquids offer the opportunity of tailoring their properties by changing the
      chemical structure of the cation and anion. Blending of two or more liquids adds
      a further dimension to this "chemical space". Here we present the results of a
      study of three binary and one ternary mixture of the ionic liquids formed by the
      N-butyl-N-methylpyrrolidinium cation with bis(trifluoromethanesulfonyl) imide,
      bis(pentafluoroethanesulfonyl) imide and
      (trifluoromethanesulfonyl)(nonafluorobutanesulfonyl) imide. We have collected
      viscosity and NMR-based data on ionxion correlations (NOE) and diffusion (DOSY).
      We also attempt to establish a quantitative correlation between mixture and the
      corresponding pure liquid properties. We find that the binary mixture containing
      the two very different anions has an intriguing and somewhat anomalous behaviour.

PMID- 20145844
TI  - On the electrodeposition of tantalum from three different ionic liquids with the
      bis(trifluoromethyl sulfonyl) amide anion.
AB  - The electrodeposition of Ta from TaF(5) was studied in three different ionic
      liquids, namely in 1-butyl-1-methylpyrrolidinium bis(trifluoromethyl sulfonyl)
      amide, 1-ethyl-3-methylimidazolium bis(trifluoromethyl sulfonyl) amide and 1
      methyl-3-propyl imidazolium bis(trifluoromethyl sulfonyl) amide. The
      electrochemical quartz crystal microbalance (EQCM) was used together with
      electrochemical techniques for characterizing in situ the electrodeposition
      process. With the help of the EQCM we could identify the stoichiometry of the
      electrodeposited species. Furthermore, square-wave voltammery was used to study
      intermediate reduction processes in the potential regime where no mass change was
      detected. An XPS analysis proved the existence of elemental Ta, besides some
      oxides and Ta halide species. Both the ionic liquid and the deposition conditions
      influence strongly the quality and properties of the deposited layers.

PMID- 20145845
TI  - Size control and immobilization of gold nanoparticles stabilized in an ionic
      liquid on glass substrates for plasmonic applications.
AB  - Gold (Au) nanoparticles were prepared by sputter deposition of Au metal in an
      ionic liquid (IL) of 1-butyl-3-methylimidazolium hexafluorophosphate (BMI-PF6).
      The size of Au nanoparticles was increased from 2.6 to 4.8 nm by heat treatment
      at 373 K. The nanoparticles uniformly dispersed in the IL were densely
      immobilized on a glass substrate surface modified with a silane coupling agent
      having an imidazole functional group by spreading the Au particle IL solution on
      the substrates, followed by heat treatment at 373 K. The optical property of the
      thus-obtained films was tunable by controlling the size of Au nanoparticles in
      the IL and the degree of immobilization. An intense localized surface plasmon
      resonance (LSPR) peak was observed in each Au particle film, and the wavelength
      of the LSPR peak could be controlled by changing the size of nanoparticles in the
      IL solution before immobilization. Photoexcitation of the LSPR peak caused
      enhancement of the photoluminescence of CdTe nanoparticles immobilized on Au
      nanoparticle films, probably due to the locally enhanced electric field formed
      around Au nanoparticles.

PMID- 20145846
TI  - Selective removal of acetylenes from olefin mixtures through specific
      physicochemical interactions of ionic liquids with acetylenes.
AB  - Imidazolium-based ionic liquids (ILs) bearing an alkylphosphite anion, were
      highly efficient for the selective removal of acetylenes in olefins. Comparison
      of solubility data at 313 K and at atmospheric pressure shows that the
      solubilities of acetylene and propyne in 1,3-dimethylimidazolium methylphosphite
      ([DMIM][MeHPO(3)]) are about 45 and 20 times higher than those of ethylene and
      propylene, respectively. Computational and (1)H NMR results clearly demonstrate
      that there are substantial interactions between the acidic hydrogen atom or atoms
      of acetylenes and the phosphite anion.

PMID- 20145847
TI  - Electrostatic properties of liquid 1,3-dimethylimidazolium chloride: role of
      local polarization and effect of the bulk.
AB  - The molecular polarization in a 1,3-dimethylimidazolium chloride ([DMIM][Cl])
      ionic liquid is analyzed for a bulk liquid via the Car-Parrinello approach. The
      analysis reveals that the electric dipole moments of cations and anions are
      characterized by large fluctuations, however these are primarily due to the
      molecules in the immediate surroundings. These results on one hand shed light on
      some basic physical and chemical features of this liquid, and on the other
      represent a fundamental handle for the development of accurate classical force
      fields; this aspect is extensively discussed and some suggestions are made.

PMID- 20145848
TI  - Ab initio study on SN2 reaction of methyl p-nitrobenzenesulfonate and chloride
      anion in [mmim][PF6].
AB  - A S(N)2 reaction of methyl p-nitrobenzenesulfonate (p-NBS) and chloride anion in
      ionic liquid ([mmim][PF(6)]) was studied using RISM-SCF-SEDD method coupled with
      a highly sophisticated ab initio electronic structure theory (CCSD). The
      solvation structure as well as the energy profile along the reaction were
      discussed through comparison with an ordinary solvent system, dichloromethane.

PMID- 20145849
TI  - A comparison of the cyclic voltammetry of the Sn/Sn(II) couple in the room
      temperature ionic liquids N-butyl-N-methylpyrrolidinium dicyanamide and N-butyl-N
      methylpyrrolidinium bis(trifluoromethylsulfonyl)imide: solvent induced changes of
      electrode reaction mechanism.
AB  - The Sn/Sn(II) couple is studied in the room temperature ionic liquids N-butyl-N
      methylpyrrolidinium dicyanamide, [C(4)mpyrr][N(CN)(2)] and N-butyl-N
      methylpyrrolidinium bis(trifluoromethylsulfonyl)imide, [C(4)mpyrr][NTf(2)] using
      cyclic voltammetry. The Sn(II) species is introduced into each of the ionic
      liquids by dissolving either SnCl(2) or Sn(CF(3)SO(3))(2). The diffusion
      coefficient of the Sn(II) species produced is found to vary with the ionic
      liquid, partly reflecting the difference in the viscosity of the two liquids, but
      also to vary with the Sn(II) salts used, indicating that different Sn(II) species
      may be present. The mechanism for the stripping of deposited tin is found to
      change with potential and also vary with the Sn(II) salt/ionic liquid combination
      used. In [C(4)mpyrr][N(CN)(2)] the mechanism for the tin stripping process is
      broadly similar for both of the Sn(II) salts used indicating that the morphology
      of the tin deposit is similar and that the stripping mechanism is largely
      independent of the Sn(II) salt anion. In [C(4)mpyrr][NTf(2)] a large difference
      was seen in the voltammetry of the different Sn(II) salts. Tafel analysis is used
      to show that the mechanism of the oxidation of Sn is sensitive to the solvent,
      the salt and the potential. The rate determining step was found to vary between
      the first electron transfer, the second electron transfer and a step likely
      involving reactions of a Sn(+) intermediate.

PMID- 20145850
TI  - Nitrile-functionalized pyrrolidinium ionic liquids as solvents for cross-coupling
      reactions involving in situ generated nanoparticle catalyst reservoirs.
AB  - A series of nitrile-functionalized pyrrolidinium-based ionic liquids have been
      prepared and characterized by spectroscopic methods and X-ray crystallography.
      The application of these new ionic liquids as reaction media for Suzuki and
      Stille C-C cross-coupling reactions has been investigated and compared with
      related imidazolium and pyridinium systems (including those with and without
      nitrile functionalities). The nature of the ionic liquid strongly influences the
      catalyzed reaction and it would appear that, in addition to the nitrile group,
      the strength of anion-cation pairing in the ionic liquid and the viscosity of the
      ionic liquid play critical roles. Nanoparticles are also detected following
      catalysis and their role, and the influence of the ionic liquid on them, is
      assessed. The ability to use the nitrile-functionalized pyrrolidinium-based ionic
      liquids diluted in other (non-functionalized) ionic liquids is also described.

PMID- 20145851
TI  - Solid and liquid charge-transfer complex formation between 1-methylnaphthalene
      and 1-alkyl-cyanopyridinium bis{(trifluoromethyl)sulfonyl}imide ionic liquids.
AB  - Liquid charge-transfer (CT) complexes were observed to form on contacting
      electron-rich aromatics with electron withdrawing group appended 1-alkyl-4
      cyanopyridinium ionic liquids (ILs). Cooling below the melting point of the ionic
      liquid resulted in crystallisation of ionic liquid from the complex for 2-cyano
      and 3-cyano pyridinium isomers and in the formation of a 1 : 1 IL : aromatic
      crystalline CT-complex with the 4-cyanopyridinium isomer. The liquid structure of
      a 1 : 1 mixture of 1-methyl-4-cyanopyridinium bis{(trifluoromethyl)sulfonyl}imide
      with 1-methylnaphthalene has been probed by neutron diffraction experiments and
      molecular dynamics simulations. A high degree of correlation between the
      experimental data and the simulations was found with a significant displacement
      of the anions from around the cation by the aromatic species and the resulting
      structure having pi-pi stacks between the cations and the aromatic.

PMID- 20145852
TI  - States and migration of an excess electron in a pyridinium-based, room
      temperature ionic liquid: an ab initio molecular dynamics simulation exploration.
AB  - The structural and electronic properties of an excess electron (EE) in the ionic
      liquid (IL) 1-methylpyridinium chloride were explored using ab initio molecular
      dynamics simulations and quantum chemical calculations to give an overall
      understanding of the solvation and transport behavior of an EE in this IL. The
      results show that the EE resides in cation pi*-type orbitals and that the
      electronic states can be characterized by the alternating appearance of localized
      and delocalized states during the time evolution. The characters of the EE
      electronic states are determined by the number of cations contributing to the
      LUMO of the IL. In a localized state one or two cations contribute to the LUMO of
      the bulk ionic liquid, while in the delocalized state the IL LUMO is composed of
      pi*-type orbitals spanning nearly all the cations in the cell. The arrangement
      and fluctuation-induced changes of the orbital components in the empty band
      produce an alternation of different states and leads to the migration of the
      excess electron. These findings can be attributed to the special features of the
      electronic structures and geometries of the IL, and they can be used to explain
      similarities and differences between pyridinium-based and imidazolium-based ILs
      in mediating electron migration.

PMID- 20145853
TI  - Double layer, diluent and anode effects upon the electrodeposition of aluminium
      from chloroaluminate based ionic liquids.
AB  - The deposition of aluminium from a chloroaluminate based ionic liquid was studied
      to elucidate the effect of a diluent (toluene) and electrolyte (LiCl) on the
      deposit morphology. A wide variety of analytical techniques was applied to this
      system to determine the speciation and mechanism of material growth. These
      included: (27)Al NMR, FAB-MS, cyclic voltammetry, chronocoulometry,
      chronopotentiometry, scanning electron microscopy and atomic force microscopy. It
      was found that under-potential deposition (upd) causes a change in the way in
      which metal grows on the electrode surface. Metal grows in two regimes which are
      believed to be nano-material and bulk material. The addition of toluene causes a
      change in speciation and a decrease in upd which in turn changes the morphology
      of the deposit obtained and can lead to mirror finish aluminium. The addition of
      LiCl has the opposite effect encouraging upd and leading to larger crystallites
      and a dark grey deposit. It is also shown for the first time that under many
      conditions the rate of the anodic dissolution process is overall rate controlling
      and one effect of the addition of toluene is to increase the rate of anodic
      dissolution.

PMID- 20145854
TI  - Ionic liquids through the looking glass: theory mirrors experiment and provides
      further insight into aromatic substitution processes.
AB  - Aromatic substitution of 1-fluoro-2,4-dinitrobenzene has been shown to proceed
      more rapidly in an ionic liquid than in ethanol, primarily due to entropic,
      rather than enthalpic, effects. By using molecular dynamics simulations, an anion
      pi interaction appears to contribute to strong ordering within the starting
      material complex that accounts for the relative differences in the S(N)Ar k.

PMID- 20145855
TI  - Ionic liquid as plasticizer for europium(III)-doped luminescent poly(methyl
      methacrylate) films.
AB  - Flexible luminescent polymer films were obtained by doping europium(III)
      complexes in blends of poly(methyl methacrylate) (PMMA) and the ionic liquid 1
      hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C(6)mim][Tf(2)N].
      Different europium(III) complexes have been incorporated in the polymer/ionic
      liquid matrix: [C(6)mim][Eu(nta)(4)], [C(6)mim][Eu(tta)(4)], [Eu(tta)(3)(phen)]
      and [choline](3)[Eu(dpa)(3)], where nta is 2-naphthoyltrifluoroacetonate, tta is
      2-thenoyltrifluoroacetonate, phen is 1,10-phenanthroline, dpa is 2,6
      pyridinedicarboxylate (dipicolinate) and choline is the 2-hydroxyethyltrimethyl
      ammonium cation. Bright red photoluminescence was observed for all the films upon
      irradiation with ultraviolet radiation. The luminescent films have been
      investigated by high-resolution steady-state luminescence spectroscopy and by
      time-resolved measurements. The polymer films doped with beta-diketonate
      complexes are characterized by a very intense (5)D(0)-->(7)F(2) transition (up to
      15 times more intense than the (5)D(0)-->(7)F(1)) transition, whereas a marked
      feature of the PMMA films doped with [choline](3)[Eu(dpa)(3)] is the long
      lifetime of the (5)D(0) excited state (1.8 ms).

PMID- 20145856
TI  - J-aggregation of ionic liquid solutions of meso-tetrakis(4
      sulfonatophenyl)porphyrin.
AB  - The title porphyrin was dissolved in the hydrophilic ionic liquid 1-butyl-3
      methylimidazolium tetrafluoroborate, [bmim][BF(4)], and triggered to assemble
      into J-aggregates by the addition of incremental volumes of water containing
      various amounts of acid (0.1, 0.2, or 1.0 M HCl). In contrast to recent studies,
      the current investigation is unique in that it centers on media that contain a
      predominant ionic liquid component (2.9-5.4 M [bmim][BF(4)]), as opposed to an
      aqueous electrolyte containing a small fraction of ionic liquid as dissociated
      solute. Complex aggregation and underlying photophysical behavior are revealed
      from absorption spectroscopy, steady-state fluorescence, and resonance light
      scattering studies. Upon addition of aqueous HCl, the efficient formation of
      H(4)TPPS(2-) J-aggregates from the diprotonated form of meso-tetrakis(4
      sulfonatophenyl)porphyrin (H(2)TPPS(4-)) occurs in [bmim][BF(4)]-rich media in a
      manner highly dependent upon the acidity, TPPS concentration, and solvent
      composition. The unique features of TPPS aggregation in this ionic liquid were
      elucidated, including the surprising disassembly of J-aggregates at higher
      aqueous contents, and our results are described qualitatively in terms of the
      molecular exciton theory. Finally, the potential of this system for the optical
      sensing of water at a sensitivity below 0.5 wt% is demonstrated. Overall, our
      findings accentuate how little is known about functional self-assembly within
      ionic liquids and suggest a number of avenues for exploring this completely
      untouched research landscape.

PMID- 20145857
TI  - Designer molecular probes for phosphonium ionic liquids.
AB  - Investigations into the extent of structuring present in phosphonium based ionic
      liquids (ILs) have been carried out using photochromic molecular probes. Three
      spiropyran derivatives containing hydroxyl (BSP-1), carboxylic acid (BSP-2) and
      aliphatic chain (C(14)H(29)) (BSP-3) functional groups have been analysed in a
      range of phosphonium based ionic liquids and their subsequent physico-chemical
      interactions were reported. It is believed that the functional groups locate the
      probe molecules into specific regions based upon the interaction of the
      functional groups with particular and defined regions of the ionic liquid. This
      structuring results in thermodynamic, kinetic and solvatochromic parameters that
      are not predictable from classical solvent models. BSP-1 and BSP-2 exhibit
      generally negative entropies of activation ranging from -50 J K(-1) mol(-1) to 
      90 J K(-1) mol(-1) implying relatively low solvent-solute interactions and
      possible anion interactions with IL polar functional groups. Higher than expected
      activation energies of 60 kJ mol(-1) to 100 kJ mol(-1) obtained for polar probes
      maybe be due to IL functional groups competing with the charged sites of the
      merocyanine (MC) isomer thus reducing MC stabilisation effects. Differences in
      thermal relaxation rate constants (2.5 x 10(-3) s(-1) in BSP-1 and 3 x 10(-4) s(
      1) in BSP-2 in [P(6,6,6,14)][dbsa]) imply that while the polar probe systems are
      primarily located in polar/charged regions, each probe experiences slightly
      differing polar domains. BSP-3 entropies of activation are positive and between
      30 J K(-1) mol(-1) to 66 J K(-1) mol(-1). The association of the non-polar
      functional group is believed to locate the spiropyran moiety in the interfacial
      polar and non-polar regions. The thermal relaxation of the MC form causes solvent
      reorientation to accommodate the molecule as it reverts to its closed form. Slow
      thermal relaxation rate constants were obserevd in contrast to high activation
      energies (5 x 10(-4) s(-1) and 111.91 kJ mol(-1) respectively, for BSP-3 in
      [P(6,6,6,14)][dbsa]). This may be due to steric effects arising from proposed
      nano-cavity formation by the alkyl chains in phosphonium based ILs.

PMID- 20145858
TI  - Insights into the surface composition and enrichment effects of ionic liquids and
      ionic liquid mixtures.
AB  - A systematic study of ionic liquid surfaces by angle resolved X-ray photoelectron
      spectroscopy (ARXPS) is presented. By reviewing recent and presenting new results
      for imidazolium-based ionic liquids (ILs), we discuss the impact of chemical
      differences on surface composition and on surface enrichment effects. (1) For the
      hydrophilic ethylene glycol (EG) functionalised ILs [Me(EG)MIm][Tf(2)N],
      [Et(EG)(2)MIm][Tf(2)N] and [Me(EG)(3)MIm][Tf(2)N], which vary in the number of
      ethylene glycol units (from 1 to 3), we find that the surface composition of the
      near-surface region is in excellent agreement with the bulk composition, which is
      attributed to attractive interactions between the oxygen atoms on the cation to
      the hydrogen atoms on the imidazolium ring. (2) For [C(n)C(1)Im][Tf(2)N] (where n
      = 1-16), i.e. ILs with an alkyl chain of increasing length, an enrichment of the
      aliphatic carbons is observed for longer chains (n > 2), at the expense of the
      polar cation head groups and the anions in the first molecular layer, both of
      which are located approximately at the same distance from the outer surface. (3)
      To study the influence of the anion on the surface enrichment, we investigated
      ten ILs [C(8)C(1)Im][X] with the same cation, but very different anions [X](-).
      In all cases, surface enrichment of the cation alkyl chains is found, with the
      degree of enrichment decreasing with increasing size of the anion, i.e., it is
      most pronounced for the smallest anions and least pronounced for the largest
      anions. (4) For the IL mixture [C(2)C(1)Im][Tf(2)N] and [C(12)C(1)Im][Tf(2)N] we
      find a homogeneous distribution in the outermost surface region with no specific
      enrichment of the [C(12)C(1)Im](+) cation.

PMID- 20145859
TI  - Solid-state dye-sensitized solar cells using polymerized ionic liquid electrolyte
      with platinum-free counter electrode.
AB  - A polymerized ionic liquid electrolyte and platinum-free counter electrode are
      employed for solid-state DSSCs. We are able to prepare a thin polymer electrolyte
      layer on nanocrystalline TiO(2) in order to reduce the cell resistance. In
      addition, an electron conductive polymer (PEDOT/PSS) or a single-wall carbon
      nanotube gel is used with the cell as an inexpensive counter electrode instead of
      platinum. The overall photon-to-current conversion efficiency was 3.7% in this
      study.

PMID- 20145860
TI  - Electrostatic interactions in ionic liquids: the dangers of dipole and dielectric
      descriptions.
AB  - Ionic liquids have attracted a great deal of attention as media for chemical
      processes, but many fundamental questions about their behavior remain unanswered.
      Their electrostatic character remains particularly mysterious, and a number of
      theoretical studies have attempted to address it using various models. These
      models often make use of a dipolar description of the charge distribution of an
      ion, or the dielectric continuum model for the medium. In this work, we review
      these approaches and show that their application to ionic liquids is questionable
      on fundamental physical grounds. While not formally incorrect, the descriptions
      are prone to certain conceptual or numerical errors when applied to molecular
      ionic systems. We highlight these problems, and discuss some alternative
      approaches currently in the literature.

PMID- 20145861
TI  - Influence of imidazolium bis(trifluoromethylsulfonylimide)s on the rotation of
      spin probes comprising ionic and hydrogen bonding groups.
AB  - The influence of the alkyl chain length in 1-alkyl-3-methylimidazolium
      bis(trifluoromethylsulfonylimide)s is studied to explore the rotation of
      piperidine-1-yloxyl derivatives substituted with either hydrogen bonding hydroxy
      group or ionic substituents, such as the cationic trimethylammonium or the
      anionic sulfate group placed at the 4 position. Structural variation of the ionic
      liquids results in differences of their viscosity influencing the rotation of the
      spin probes. The size of the average rotational correlation times of the spin
      probes dissolved in the ionic liquids depends further on the additional
      substituent in 4-position at these spin probes. The rotational correlation time
      exhibits a linear dependence on the ionic liquid viscosity in the case of the
      spin probe forming hydrogen bonding with the ionic liquids. In contrast to this,
      a deviation from the Stokes-Einstein behavior is found in the case of rotation of
      the charged spin probes in the 1-alkyl-3-methylimidazolium
      bis(trifluoromethylsulfonylimide)s substituted with a longer alkyl chain. This
      effect may be explained by phase separation on a molecular level between the
      charged part of the ionic liquid and the longer alkyl chains bound at the
      imidazolium ion. Although the neutral and the cationic spin probes show only a
      slight dependence between ionic liquid structure variation and the hyperfine
      coupling constants, structural effects cause changes in the hyperfine coupling
      constants in the case of the anionic spin probes. These probes strongly interact
      with the imidazolium ion.

PMID- 20145862
TI  - NMR spectroscopic studies of cellobiose solvation in EmimAc aimed to understand
      the dissolution mechanism of cellulose in ionic liquids.
AB  - The dissolution mechanism of cellulose in ionic liquids has been investigated by
      using cellobiose and 1-ethyl-3-methylimidazolium acetate (EmimAc) as a model
      system under various conditions with conventional and variable-temperature NMR
      spectroscopy. In DMSO-d(6) solution, NMR data of the model system clearly suggest
      that hydrogen bonding is formed between hydroxyls of cellobiose and both anion
      and cation of EmimAc. The CH(3)COO(-) anion favors the formation of hydrogen
      bonds with hydrogen atoms of hydroxyls, and the aromatic protons in bulky cation
      [Emim](+), especially the most acidic H2, prefer to associate with the oxygen
      atoms of hydroxyls with less steric hindrance, while after acetylation of all
      hydroxyls in cellobiose the interactions between cellobiose octaacetate and
      EmimAc become very weak, implying that hydrogen bonding is the major reason of
      cellobiose solvation in EmimAc. Meanwhile the stoichiometric ratio of
      EmimAc/hydroxyl is estimated to be between 3:4 and 1:1 in the primary solvation
      shell, suggesting that there should be one anion or cation to form hydrogen bonds
      with two hydroxyl groups simultaneously. In situ and variable-temperature NMR
      spectra suggest the above mechanism also works in the real system.

PMID- 20145863
TI  - Ionic liquids and reactive azeotropes: the continuity of the aprotic and protic
      classes.
AB  - In this work, we explore the relations between the acid-base reactions implicit
      in the definition of protic ionic liquids and their solutions, the existence of
      reactive azeotropy, and the continuity between the aprotic and protic classes of
      ionic liquids. The profound impact caused by this type of homogenous azeotropy on
      the fluid phase behaviour (liquid-gas equilibria) of this class of compounds is
      also discussed.

PMID- 20145864
TI  - Electrochemical carboxylation of alpha-chloroethylbenzene in ionic liquids
      compressed with carbon dioxide.
AB  - Electrochemical carboxylation is conducted in ionic liquids compressed with
      carbon dioxide. It is found that the current efficiency increases with
      temperature and pressure. The diffusion coefficient of the substrate, which is
      obtained from the electrochemical measurements, also remarkably increases with
      temperature and pressure. The increase of the current efficiency is mainly
      explained by improvement in the mass transfer, and the promotion of the
      electrochemical carboxylation in the ionic liquid is achieved by pressurizing the
      carbon dioxide moderately.

PMID- 20145865
TI  - A theoretical study of the copper(I)-catalyzed 1,3-dipolar cycloaddition reaction
      in dabco-based ionic liquids: the anion effect on regioselectivity.
AB  - The regioselectivity of copper(I)-catalyzed synthesis of 1,2,3-triazoles in dabco
      based ionic liquids has been investigated at the DFT level using a supermolecular
      approach. The analysis of the theoretical results shows that the coordination
      ability of the ionic liquid (IL) anion to copper(I) catalyst and to all the other
      species containing the copper (intermediates and transition states) can
      significantly affect product distribution. Possible catalyst sequestering effects
      and the ability to stabilize selectively new intermediate species have been
      envisaged, as probable mechanisms throughout IL anions can affect copper
      catalyzed reactions inside performed.

PMID- 20145866
TI  - Reactions of excited-state benzophenone ketyl radical in a room-temperature ionic
      liquid.
AB  - The photochemistry of the benzophenone ketyl radical in D(1) excited state,
      BPH(D(1)), was studied by means of two-color dual-pulse laser flash photolysis
      (355 and 532 nm) in a room-temperature ionic liquid, 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)amide (Bmim-TFSA), and in methanol. Upon excitation
      with the 532 nm pulse, BPH(D(1)) emitted strong fluorescence. The transient
      absorption and fluorescence spectra of BPH(D(1)) were measured with nanosecond
      and sub-nanosecond time resolution, respectively. The observed Stokes shift was
      1700 cm(-1) in Bmim-TFSA, and this shift was close to that in acetonitrile. The
      fluorescence lifetime of BPH(D(1)) was determined to be 5 ns in Bmim-TFSA, and
      again the value was close to that in acetonitrile. The rate constant of the
      reaction of BPH(D(1)) with CCl(4) in Bmim-TFSA was determined to be (2.1 +/- 0.4)
      x 10(9) M(-1) s(-1), which was 10 times the rate constant calculated on the basis
      of the bulk viscosity of Bmim-TFSA. The results are discussed in terms of the
      effective microscopic viscosity of the ionic liquid that was recently reported
      for the cage effect.

PMID- 20145868
TI  - An ultra high vacuum-spectroelectrochemical study of the dissolution of copper in
      the ionic liquid (N-methylacetate)-4-picolinium
      bis(trifluoromethylsulfonyl)imide.
AB  - Ultra high vacuum-spectroelectrochemistry was used to investigate the
      electrochemically generated Cu species in the ionic liquid (N-methylacetate)-4
      picolinium bis(trisfluoromethylsulfonyl)imide, [MAP][Tf(2)N]. The diffusion of
      Cu(+) across the surface of the ionic liquid was monitored in situ by X-ray
      photoelectron spectroscopy (XPS). A numerical procedure was developed to simulate
      the surface process from which, the apparent diffusion coefficient of Cu(+)
      across the surface is estimated to be 3.5 x 10(-5) cm(2) s(-1). Bulk diffusion
      process of Cu(+) in [MAP][Tf(2)N] was investigated ex situ for comparison with
      the surface process.

PMID- 20145867
TI  - Nanocomposites of ionic liquids confined in mesoporous silica gels: preparation,
      characterization and performance.
AB  - A series of nanocomposites of ionic liquids (ILs) were prepared via a modified
      sol-gel method. The ILs were physically confined in mesoporous silica gels with 5
      40% content. ILs from imidazolium, thiophenium and ammonium with different anions
      were prepared and used. Characterization using the Brunauer-Emmett-Teller (BET)
      method, Fourier transform infrared (FT-IR) spectroscopy, temperature-programmed
      desorption (TPD), differential scanning calorimetry (DSC), inverse gas
      chromatography (IGC), temperature-controlled Raman and fluorescence emission
      spectroscopies was conducted to explore any confinement effects. BET results
      showed that, depending on the ILs and their contents, the average pore diameter
      of the pure silica gel was 3-12 nm after the confined ILs were removed
      completely. It was suggested that ILs aggregated on the nanoscale in the
      mesoporous silica gel. In comparison with bulk ILs and ILs coated onto silica
      gels (IL/sg), IL nanocomposites (IL-sg) displayed remarkably low specific heat
      capacities (C(p) was in the range 0.3-1.2 J g(-1) K(-1)), disordered vibrational
      conformations (without phase transitions in the range -100-200 degrees C),
      greater interactions with hydrocarbon solutes (adsorption capacities of 0.3-0.4 g
      per 100 g for confined ILs with CO(2) gas), and greatly enhanced fluorescence
      emission (up to 200 times stronger than bulk ILs). Furthermore, Based on the
      specific solubility of different compounds, the nanocomposites could also be
      applied to the separation of CO(2) from CO(2)/N(2) mixtures and thiophene from
      thiophene/octane mixtures.

PMID- 20145869
TI  - A COSMO-RS based guide to analyze/quantify the polarity of ionic liquids and
      their mixtures with organic cosolvents.
AB  - A COSMO-RS descriptor (S(sigma-profile)) has been used in quantitative structure
      property relationship (QSPR) studies by a neural network (NN) for the prediction
      of empirical solvent polarity E(T)(N) scale of neat ionic liquids (ILs) and their
      mixtures with organic solvents. S(sigma-profile) is a two-dimensional quantum
      chemical parameter which quantifies the polar electronic charge of chemical
      structures on the polarity (sigma) scale. Firstly, a radial basis neural network
      exact fit (RBNN) is successfully optimized for the prediction of E(T)(N), the
      solvatochromic parameter of a wide variety of neat organic solvents and ILs,
      including imidazolium, pyridinium, ammonium, phosphonium and pyrrolidinium
      families, solely using the S(sigma-profile) of individual molecules and ions.
      Subsequently, a quantitative structure-activity map (QSAM), a new concept
      recently developed, is proposed as a valuable tool for the molecular
      understanding of IL polarity, by relating the E(T)(N) polarity parameter to the
      electronic structure of cations and anions given by quantum-chemical COSMO-RS
      calculations. Finally, based on the additive character of the S(sigma-profile)
      descriptor, we propose to simulate the mixture of IL-organic solvents by the
      estimation of the S(sigma-profile)(Mixture) descriptor, defined as the weighted
      mean of the S(sigma-profile) values of the components. Then, the E(T)(N)
      parameters for binary solvent mixtures, including ILs, are accurately predicted
      using the S(sigma-profile)(Mixture) values from the RBNN model previously
      developed for pure solvents. As result, we obtain a unique neural network tool to
      simulate, with similar reliability, the E(T)(N) polarity of a wide variety of
      pure ILs as well as their mixtures with organic solvents, which exhibit
      significant positive and negative deviations from ideality.

PMID- 20145870
TI  - Fragility, Stokes-Einstein violation, and correlated local excitations in a
      coarse-grained model of an ionic liquid.
AB  - Dynamics of a coarse-grained model for the room-temperature ionic liquid, 1-ethyl
      3-methylimidazolium hexafluorophosphate, couched in the united-atom site
      representation are studied via molecular dynamics simulations. The dynamically
      heterogeneous behavior of the model resembles that of fragile supercooled
      liquids. At or close to room temperature, the model ionic liquid exhibits slow
      dynamics, characterized by nonexponential structural relaxation and subdiffusive
      behavior. The structural relaxation time, closely related to the viscosity, shows
      a super-Arrhenius behavior. Local excitations, defined as the displacement of an
      ion exceeding a threshold distance, are found to be mainly responsible for
      structural relaxation in the alternating structure of cations and anions. As the
      temperature is lowered, excitations become progressively more correlated. This
      results in the decoupling of exchange and persistence times, reflecting a
      violation of the Stokes-Einstein relation.

PMID- 20145871
TI  - In search of pure liquid salt forms of aspirin: ionic liquid approaches with
      acetylsalicylic acid and salicylic acid.
AB  - We present an ionic liquid (IL) approach towards a dual functional liquid salt
      form of aspirin using different pharmaceutically active cations composed of
      antibacterials, analgesics, local anesthetics, and antiarrhythmic drugs in
      combination with acetylsalicylic acid or its metabolite salicylic acid and
      discuss stability of these ILs in comparison to solid salts. Several low-melting
      or liquid salts of salicylic acid with dual functionality and promising
      properties were isolated and characterized; however, although such ILs with
      aspirin could be prepared, they suffer from limited stability and slowly
      decompose into the corresponding salicylate ILs when exposed to moisture.

PMID- 20145872
TI  - Understanding siloxane functionalised ionic liquids.
AB  - In this paper we use ab initio theoretical methods in combination with
      experimental studies to investigate ion-pairs of the ionic liquid (IL) 1-methyl-3
      pentamethyldisiloxymethylimidazolium chloride [(SiOSi)C(1)C(1)im]Cl, in order to
      deepen our understanding of the effects of functionalisation on an IL. In
      addition, we focus on the effect of the siloxy group on the viscosity. We
      establish that the ion-pairing energies of [(SiOSi)C(1)C(1)im]Cl are similar to
      those of 1-butyl-3-methylimidazolium chloride [C(4)C(1)im]Cl, because the anion
      interacts primarily with the imidazolium ring. A large range of ion-pair
      structural configurations is possible with different anion positions and chain
      orientations, contributing to a significant entropy. A H-bonded network forms,
      however the siloxy chain can shield the Cl(-) or key C-H sites thus introducing
      defects. Despite a significant increase in mass relative to [C(4)C(1)im](+), the
      combined barriers to rotation within the substituent chain are substantially
      reduced in [(SiOSi)C(1)C(1)im](+), this is primarily due to the flexibility of
      the siloxane linkage, and free rotation of the Si-Me methyl groups. The most
      important effect is a coupling of rotational motions within the chain which leads
      to dynamic inter-conversion of cation conformers, and facilitates movement of the
      anion around the cation, these will contribute to enhanced transport properties
      and a reduced viscosity. In addition, a longer charge arm is expected to enhance
      rotational and rotational-translational coupling in electric fields. Thus, for
      [(SiOSi)C(1)C(1)im]Cl ion-pair association is very similar to that of
      [C(4)C(1)im]Cl, but "dynamic" properties relating to torsional motion, a dynamic
      H-bonded network, and cation response to an external electric field are enhanced.

PMID- 20145878
TI  - Coupling indigenous biostimulation and phytoremediation for the restoration of
      2,4,6-trinitrotoluene-contaminated sites.
AB  - In-situ bioremediation has been highly promising in degrading nitroaromatics in
      soil, e.g., 2,4,6-trinitrotoluene (TNT). The case of TNT is examined here as a
      representative nitroaromatic compound that belongs to a suite of explosive
      residue types scattered throughout the European Union and other areas of the
      world. Differences in cost-effectiveness and TNT degradation rates between
      existing methods have spurred extensive debate in bioremediation research of
      explosive-contaminated sites. Rhizoremediation (plant inoculation with a specific
      microorganism), including genetic modification of plant/tree species, has been
      treated as the next best remediation method due to excellent performance in the
      lab. However, recent data collected in the field do not support the initial
      enthusiasm, showing in many cases, no statistical difference between (non
      )transgenic rhizoremediation and phytoremediation (use of wild plant types).
      Obviously, the role of indigenous rhizospheric microorganisms has been
      underestimated, impeding our progress towards identifying the critical components
      of the optimum bioremediation scheme. Future research directions to enhance the
      indigenous microbial activity in the plant rhizosphere via addition of chemical
      amendments, such as, nutrients (fertilizers), and/or chaotropic agents (urea)
      could improve the overall efficiency of existing phytoremediation schemes.

PMID- 20145879
TI  - Electrochemical degradation of 17-alpha-ethinylestradiol (EE2) and estrogenic
      activity changes.
AB  - 17-alpha-ethinylestradiol (EE(2)) as one of typical representatives of steroid
      estrogens is detrimental to endocrine systems of animals and humans due to its
      potential estrogenic activity. The degradation of EE(2) in aquatic solution by
      electrocatalytic oxidation applying Ti-based SnO(2) (Ti/SnO(2)) electrode as the
      anode was investigated. A pseudo-first-order kinetics under various initial
      concentrations of EE(2) was obtained and it was found that the calculated kinetic
      constant was determined as 0.112 min(-1), 0.053 min(-1), 0.023 min(-1) and 0.019
      min(-1), which tended to rise in inverse proportion to EE(2) concentration within
      selected content of EE(2) as 0.5 mg L(-1), 2.0 mg L(-1), 5 mg L(-1) and 10 mg L(
      1). Frozen recombinant yeast was introduced to evaluate estrogenic activities of
      an aqueous solution of 2.0 mg L(-1) EE(2) and oxidation products. The
      concentration of EE(2) and EE(2) equivalents (EEEQs) decayed 96.5%, 96.3%
      respectively in 15 min and 78.5% reduction of TOC in 8 h was observed under
      current density conditions of 10 mA cm(-2) and 0.2 M Na(2)SO(4) as the
      electrolyte in the process of electrolysis. On the basis of the results obtained,
      it indicates that the estrogenic activities of the intermediate products can be
      negligible.

PMID- 20145880
TI  - Atmospheric stability of arsines and the determination of their oxidative
      products in atmospheric aerosols (PM10): evidence of the widespread phenomena of
      biovolatilization of arsenic.
AB  - Biovolatilisation of arsenic as their arsines in the form of AsH(3), and mono-,
      di and trimethylarsine has often been determined under laboratory conditions.
      Although environmental point sources such as landfill sites or hot springs have
      been characterised, only limited knowledge is available on how widespread the
      formation of volatile methylated arsenic compounds are in the environment. Here
      we studied the atmospheric stability of the different arsines and quantified
      their oxidation products in atmospheric particulate matter (PM(10)) in two
      locations in Argentina. The atmospheric half-life of the arsines range from 19
      weeks for AsH(3) to 2 d for trimethylarsine (TMAs) at 20 degrees C in the dark,
      while during simulated daytime conditions the stability is reduced for all
      arsines and in particular for the methylated arsines by three orders of magnitude
      which suggests that TMAs can only be dispersed at night. At both locations the
      arsenic concentration was in all samples below 1 ng As m(-3), which is considered
      as rural background for arsenic. The oxidation products, i.e. methylarsonate
      (MA), dimethylarsinate (DMA) and trimethylarsine oxide (TMAO) were identified by
      using HPLC-ICP-MS/ES-MS in more than 90% of the 49 PM(10) samples taken from 8
      sampling points at the two geographically different locations. TMAO was the
      predominate organoarsenicals in both locations (66 and 69%, respectively) while
      DMA was determined to be between 13 and 19% of all organoarsenicals at the two
      locations. The concentration of the organoarsenicals ranged from 4 to 60 pg As as
      TMAO m(-3), while the maximum concentration for DMA and MA were 16 and 6 pg As m(
      3), respectively. No difference in terms of the concentration or distribution of
      the organoarsenicals in the PM(10) samples was identified as significant. Since
      the two locations were different in climate and industrial impact and sampled in
      different seasons, these data suggest that methylated arsenicals do occur as
      background chemicals in the environment. Due to the low atmospheric stability of
      the methylated arsines, it is suggested that biovolatilization of arsenic as
      methylated arsines is a widespread phenomenon. More studies however are necessary
      to identify the major sources and determine the flux of the volatilization
      process in order to determine whether or not the process has environmental
      significance.

PMID- 20145881
TI  - Evaluation of PAH diagnostic ratios as source apportionment tools for air
      particulates collected in an urban-industrial environment.
AB  - A variety of polycyclic aromatic hydrocarbon (PAH) diagnostic ratios were
      examined as source apportionment tools in the analysis of a PAH data set
      associated with atmospheric particulate matter collected in an urban-industrial
      environment. Seventy-six PM(10) samples were collected concurrently at 4 sampling
      sites over a one-month period in Hamilton, Ontario, Canada, a city of 500 000
      people that is home to two integrated steel companies, associated industries and
      a network of roadways and major highways. Samples collected under well defined
      meteorological conditions were categorized as being 'upwind' or 'downwind' of the
      industrial sector. All sample extracts were analyzed for 48 parent PAH,
      methylphenanthrenes and sulfur-containing aromatics and showed a thousand-fold
      range of total PAH concentrations (0.23-172 ng m(-3)). Of all PAH diagnostic
      ratios examined, the two most useful were the
      anthracene/(anthracene+phenanthrene) and
      benz[a]anthracene/(benz[a]anthracene+chrysene/triphenylene) ratios. These
      afforded the best discrimination of samples that had significant industrial
      impacts. This work is the first example of the use of a linear combination of PAH
      ratios, coupled with total PAH data and well defined local samples to determine
      the relative impacts of mobile and industrial emissions in an urban-industrial
      environment. Use of a linear combination of PAH ratios allowed us to categorize
      95% of the data as 'upwind' or 'downwind' of the industrial sector. It is
      important to determine PAH ratio threshold values based on data from well defined
      local samples rather than relying on literature values alone.

PMID- 20145882
TI  - A comparative study of two factor analytic models applied to PAH data from
      inhalable air particulate collected in an urban-industrial environment.
AB  - Two factor analysis (FA)-based receptor modeling methods were applied to a
      polycyclic aromatic hydrocarbon (PAH) dataset from extracts of 75 PM(10) air
      particulate samples collected concurrently at 4 sampling sites proximate to the
      urban-industrial area in Hamilton, Ontario, Canada. The total PAH concentrations
      of 48 target compounds ranged from 0.23 to 172 ng m(-3). Principal component
      analysis (PCA) and positive matrix factorization (PMF) analysis were followed by
      multilinear regression analyses to identify and quantify PAH source
      contributions, together with spatial and temporal trends. The correlations
      between predicted and observed total PAH levels were excellent in both models
      (R(2) > 0.98). The PCA afforded large negative contributions in a number of
      samples, so further analysis was abandoned. The PMF analysis showed 3 factors
      which were identified as gasoline emissions, diesel emissions and coke oven
      emissions. Contributions of gasoline emissions and diesel emissions factors were
      surprisingly similar at all 4 sites indicative of a background of vehicle
      emissions across the city. The PMF coke oven emission factor showed the greatest
      variability in total loadings, consistent with the large PAH emissions from the
      steel industries and the large influence of wind direction on PAH concentrations.
      The highest coke oven contributions were observed at sites closest to the
      industrial area on days when these sites were downwind of the industries. The PMF
      coke oven impact factor showed good correlations with two commonly used PAH
      diagnostic ratios when the ratios were combined into a single ratio. This
      integrated approach allowed us to categorize >90% of the samples based on the
      wind direction of the impacting source.

PMID- 20145883
TI  - Anthropogenic versus geogenic contribution to total suspended atmospheric
      particulate matter and its variations during a two-year sampling period in
      Beijing, China.
AB  - Weekly samples of total suspended particles in air (TSP) were taken in south-east
      Beijing for a two-year period continuously from August 2005 to August 2007. Mass
      concentrations varied between 76 and 1028 microg m(-3) with an average
      concentration of 370 microg m(-3) for the whole period. The chemical composition
      and the mass concentration of aerosols in combination with meteorological data
      are reflecting specific influences of distinct aerosol sources on the pollution
      of Beijing's atmosphere. Lead (Pb), titanium (Ti), zinc (Zn) and copper (Cu)
      concentrations were chosen as indicator elements for different sources. Their
      amounts considerably varied over the course of the year. Element ratios, such as
      Pb/Ti, supported the distinction between periods of predominant geogenic or
      anthropogenic caused pollution. However, the interactions between aerosols from
      different sources are numerous and aerosol pollution still is a big and complex
      challenge for the sustainable development of Beijing.

PMID- 20145884
TI  - Chromium in exhaled breath condensate (EBC), erythrocytes, plasma and urine in
      the biomonitoring of chrome-plating workers exposed to soluble Cr(VI).
AB  - Chromium (Cr) levels measured in exhaled breath condensate (EBC-Cr) and urine (Cr
      U) at the beginning and end of working shifts were related to those measured in
      erythrocytes (Cr-RBC) and plasma in 14 non-smoking male chrome-plating workers
      exposed to Cr(VI) in soluble aerosol form who did not report any significant
      current or past respiratory disease. Cr-U mainly correlated with Cr-P (Cr in
      plasma) at the end of the working shift (r(2) = 0.59, p < 0.01), whereas Cr-RBC
      correlated with EBC-Cr (r(2) = 0.32, p < 0.05); at the beginning of the shift,
      the only significant correlation was between Cr-U and Cr-RBC (r(2) = 0.74, p <
      0.01). The clearance of Cr(iii) arising from Cr(VI) reduction was rapid, thus
      making Cr-U and Cr-P ideal biomarkers of the most recent exposure, whereas Cr-RBC
      may represent the fraction of Cr(VI) that reaches the bloodstream in non-reduced
      form and therefore depends on the airway inhaled dose represented by EBC-Cr. Cr
      RBC clearance is slower and not only involves the free diffusion of Cr(iii) from
      RBC to plasma, but probably also involves more complicated kinetic phenomena
      involving other tissues and organs, which may explain the correlation between Cr
      RBC and Cr-U and the lack of correlation Cr-RBC and Cr-P at least 36 h after the
      last exposure. In conclusion, our findings reinforce the idea that measuring Cr
      in EBC can significantly contribute to traditional biomonitoring by providing
      specific information at the target organ level and integrating our knowledge of
      Cr toxicokinetics.

PMID- 20145885
TI  - Hygroscopic properties of the workroom aerosol in aluminium smelter potrooms: a
      case for transport of HF and SO2 into the lower airways.
AB  - The hygroscopic behaviour of individual aerosol particles from workplaces in a
      primary aluminium smelter was investigated by environmental scanning electron
      microscopy. At a high relative humidity, comparable with the human respiratory
      tract, most particles encountered in the Soderberg and Prebake potrooms either
      undergo partial deliquescence (leading to a water droplet with an insoluble core)
      or form thin water films at the surface. As gaseous HF and SO(2) are highly
      soluble in water, the aerosol particles may act as carrier for these two gases
      into the alveolar region of the lower respiratory tract. Based on a one
      dimensional mass balance model, it is estimated that under peak exposure
      conditions (particle surface area concentration of 10(-4) cm(2) cm(-3))
      approximately 10% of the initial gaseous HF may be transferred to the particle
      phase. For SO(2), this fraction is much lower (approximately 1%). These results
      indicate that at least HF may penetrate deeper into the lung in the presence of
      soluble particles or particles that form surface water films compared to HF
      alone.

PMID- 20145886
TI  - Remediating plastic waste into carbon nanotubes.
AB  - Polyethylene-based used plastics needs hundreds of years to degrade in
      atmospheric conditions. Thus, in addition to conventional recycling facilities
      for polymer waste (PW), innovative solutions are required. This paper describes a
      solvent-free process that converts PW such as low-density (LD) and high-density
      polyethylene (HDPE) into multi-walled carbon nanotubes (MWCNTs) via thermal
      dissociation in the presence of chemical catalysts in a closed system under
      autogenic pressure. Specifically, the optimization of process parameters, e.g.
      selection and amounts of catalysts, density effects of PE, autogenic pressure
      measurements, and a reaction mechanism for the growth of MWCNTs is explained. The
      composition, morphology, and atomic structure of the as-obtained MWCNTs are
      characterized employing advanced structural, spectroscopic, and imaging
      techniques. We have measured the unique magnetic and electrical conductivity
      behaviours of as-prepared MWCNTs to assess their potential applications as
      advanced materials. This reproducible process presents an opportunity to use PW
      as a feedstock for the production of MWCNTs, industrially significant value-added
      products. Among the known methods for the fabrication of MWCNTs, the present
      controlled dissociation of PW is one of the inexpensive and straightforward
      methods.

PMID- 20145887
TI  - Atmospheric concentrations of ammonia and nitrogen dioxide at a tropical coral
      cay with high seabird density.
AB  - Ecosystems with high seabird densities can receive extremely high inputs of
      nitrogen (N) from bird guano. Seabirds deposit up to 1000 kg N ha(-1) y(-1) on
      Heron Island, a tropical coral cay of the Great Barrier Reef. We quantified
      atmospheric concentrations of ammonia (NH(3)) and nitrogen dioxide (NO(2)) with
      passive air samplers at beach, woodland and forest along a gradient of low,
      intermediate and high bird densities, respectively. NO(2) concentrations at all
      studied sites were generally low (average 0.2-2.3 microg NO(2) m(-3)) and similar
      to other ecosystems. An exception was the main traffic zone of helicopter and
      barge traffic which had elevated concentrations (average 6.2, maximum 25 microg
      NO(2) m(-3)) comparable to traffic-intense urban areas elsewhere. Increasing
      average NH(3) concentrations from 0.7 to 17 microg NH(3) m(-3) was associated
      with greater seabird nesting density. In areas of intermediate and high bird
      density, NH(3) concentrations were substantially higher than those typically
      detected in natural and agricultural systems, supporting the notion that seabird
      guano is a major source of NH(3). The steep decline of NH(3) concentrations in
      areas with low bird density indicates that trans-island transport of NH(3) is
      low. NH(3) may not only be re-deposited in close vicinity of the source but is
      also transported vertically as concentrations above the tree canopy averaged 7.5
      microg NH(3) m(-3). How much guano-derived NH(3) contributes to reefal waters via
      the possible transfer path water --> land --> water remains to be established. We
      discuss atmospheric concentrations of NH(3) and NO(2) in context of N-based
      gaseous pollutants and effects on vegetation.

PMID- 20145888
TI  - Use of the BCR sequential extraction procedure for the study of metal
      availability to plants.
AB  - To investigate the mobility and availability of metals from soil to plant,
      concentrations of zinc (Zn), copper (Cu), lead (Pb), cadmium (Cd), mercury (Hg)
      and arsenic (As) in topsoils and plants (lettuce, scallion, celery, tomato,
      carambola, wampee and longan) collected from the area around a petrochemical
      complex in Guangzhou, China, were analyzed. The modified European Community
      Bureau of Reference (BCR) three-step sequential extraction procedure was applied
      to determine the concentration of metal fractions in soils. The results showed
      that the distribution of Zn, Cu, Pb and Cd in four fractions varied greatly among
      the soil samples, and 18.8% of vegetable and fruit samples for Cd and 5.8% for Pb
      exceeded the maximum permissible levels in food of China. Soil-to-plant transfer
      coefficients were in the order of Cd>Zn>Cu>Hg>As>Pb, suggesting Cd being the most
      mobile and available to plants among the metals studied. Principal component
      analysis indicated that metal fractions and soil physicochemical properties (pH,
      organic matter, cation exchange capacity, clay content and electrical
      conductivity) affected metal uptake by plants. Furthermore, atmospheric
      deposition may be another important factor for the accumulation of metals in
      plants.

PMID- 20145889
TI  - Elevated mercury exposure in communities living alongside the Inanda Dam, South
      Africa.
AB  - Mercury is a persistent heavy metal that has been associated with damage to the
      central nervous system, including hearing and speech impairment, visual
      constriction and loss of muscle control. In aquatic environments mercury may be
      methylated to its most toxic form, methyl-mercury. In 1990 concerns were raised
      over mercury contamination in the vicinity of a mercury processing plant in
      KwaZulu-Natal, South Africa. Mercury waste was reported to have been discharged
      into the Mngceweni River, situated in close proximity to the plant. The Mngceweni
      River joins the uMgeni River, which in turn flows into the Inanda Dam, along the
      banks of which several villages are located. This study evaluated the mercury
      levels in river and dam sediments, fish from the Inanda Dam and hair samples
      collected from residents of three villages along the banks of the Inanda Dam. The
      study results showed that 50% of the fish samples and 17% of hair samples
      collected from villagers had mercury concentrations that exceeded guideline
      levels of the World Health Organization. Mercury concentrations in 62% of the
      river sediment samples collected in close proximity to the former mercury
      processing plant exceeded the level at which remedial action is required
      according to legislation in the Netherlands. These preliminary findings give
      reasons for concern and should be used as a baseline for further investigations.

PMID- 20145890
TI  - Effect of sample filtration on the quality of monitoring data reported for
      organic compounds during wastewater treatment.
AB  - Accurate quantification of organic wastewater compounds (OWCs) is essential for
      assessing their removal efficiency in wastewater treatment plants (WWTPs) and for
      calculating discharge rates into effluent-receiving surface waters. In this
      study, we undertook a theoretical evaluation of the effect of sorption and sample
      filtration on data quality. Filtration of samples, while commonly practiced, may
      preclude a potentially significant fraction of chemical mass from both chemical
      measurements and mass flow analyses for WWTPs. Sorption theory dictates that
      analyte losses from sample filtration are notable for hydrophobic organic
      compounds (HOCs) featuring a pH-dependent logarithmically transformed organic
      carbon-water distribution coefficient (log D(OC)) of > or =3.0. Among a total of
      33 organic wastewater compounds considered, the extent of sorption to filterable
      materials ranged from 22% for bisphenol A diglycidyl ether (BADGE) to 99% for di
      (2-ethylhexyl)phthalate (DEHP). Sample filtration also was demonstrated to have a
      profound impact on the outcome of chemical fate and behavior studies. When the
      chemical mass residing on filterable particulates was considered, the
      concentration spread (range) doubled between maximum and minimum concentrations
      reported for raw wastewater. Furthermore, removal efficiencies of WWTPs
      calculated for HOCs increased by as much as 62% just by changing the method of
      accounting. We conclude that some of the data spread reported in the literature
      concerning chemical mass loadings, contaminant concentrations in raw sewage, and
      removal efficiencies of similarly designed WWTPs is driven not by actual
      differences in sewage composition, geographic locations and treatment units but
      by sample processing protocols and the method of mass accounting.

PMID- 20145891
TI  - Meteo-climatic conditions influence the contribution of endotoxins to PM10 in an
      urban polluted environment.
AB  - A decrease in inhalable particulate matter (PM10) pollution is a top priority in
      urban areas of northern Italy. The sources of PM10 are both anthropogenic and
      natural. The former have been broadly investigated while the latter are less well
      known. Endotoxins are natural compounds of PM10 and are potentially toxic.
      Endotoxins are part of the outer membrane of Gram-negative bacteria. Their health
      effects are linked to environmental exposure. The effects mainly consist of
      respiratory symptoms, including pulmonary function decline. The occurrence of
      endotoxins has been proven in several occupational environments where organic
      materials supply an optimal substrate for bacteria growth. Knowledge about the
      presence of these contaminants in the environment is limited. The aim of this
      work is to evaluate the endotoxin levels of PM10 in the urban air of Turin, and
      to investigate the influence of seasonal and meteo-climatic factors. The sampling
      was conducted from January to December 2007. Endotoxin determination was
      performed by an LAL assay after extraction optimization. The PM10 levels ranged
      from 11.90 to 104.74 microg/m(3) (48.28 +/- 23.09) while the endotoxin levels
      ranged between 0.09 and 0.94 EU/m(3) (0.42 +/- 0.23). The seasonal trends of PM10
      and endotoxin are inversely proportional. There is a statistically significant
      correlation between endotoxin and temperature (r = 0.532 p < 0.01), as well as
      between endotoxin and relative humidity (r = -0.457 p < 0.01). However,
      temperature has a predominant role. We observed that urban endotoxin
      concentrations are narrow in range and that the contribution of endotoxins to the
      total PM10 is only two millionths.

PMID- 20145892
TI  - Development of a personal dual-phase air sampling method for phthalate diesters.
AB  - Phthalates are used as plasticizers in many industrial and consumer products.
      Urinary biomonitoring has shown widespread human exposure to phthalates, with
      workers having especially high exposures. Phthalates can be present in workplace
      air as either aerosols or vapors depending on source materials, vapor pressure,
      and processing temperatures. We sought to develop a dual-phase air sampling
      method for 6 phthalates, dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n
      butyl phthalate (DBP), benzyl butyl phthalate (BzBP), di(2-ethylhexyl) phthalate
      (DEHP), and di-n-octyl phthalate (DnOP), adaptable to aerosol inlets with known
      particle collection characteristics. Collection media consisted of a quartz fiber
      filter and XAD-2 resin. Limit of detection (LOD) and limit of quantification
      (LOQ) were determined for each phthalate. Phthalate recoveries were evaluated at
      3x, 10x and 30x the LOQ, and after storage at -21 degrees C and 21 degrees C.
      Media were Soxhlet extracted in 10% diethyl ether in hexanes along with an
      extraction surrogate, di-n-pentyl phthalate-d(4). Gas chromatography/mass
      spectrometry was performed to quantify the phthalate diesters using di(2
      ethylhexyl) phthalate-d(4) as an internal standard. Estimated LODs were 1 microg
      per sample (BzBP, DEHP, and DnOP), 2 microg per sample (DMP and DBP), and 5
      microg per sample (DEP). Mean recoveries under static conditions were 85-104% for
      DBP, BzBP, DEHP, and DnOP; but <70% for DMP and DEP at 3x and 10x the LOQ. After
      air was pulled through spiked samples, DMP and DEP recoveries improved to 74-81%.
      After storage for 62 days, phthalate recovery was better at -21 degrees C than at
      21 degrees C. Method accuracy was best for DBP, BzBP, DEHP, and DnOP (range 11
      18%), and less so for DMP (28%) and DEP (29%).

PMID- 20145893
TI  - Hydrobia ulvae imposex levels at Ria de Aveiro (NW Portugal) between 1998 and
      2007: a counter-current bioindicator?
AB  - Imposex expression in prosobranch gastropods has been widely used as a biomarker
      of tributyltin (TBT) pollution. Estuaries have been described as the most
      affected areas by this problem since they usually enclose the main TBT sources-
      ports, dockyards and marinas--resulting from the compound's application as a
      biocide in antifouling paints on ships. Using Hydrobia ulvae as a bioindicator,
      the current work addresses the most reliable methods to reduce the influence of
      critical variables, such as the animals' size, on imposex levels assessment for
      TBT pollution monitoring and presents its temporal trends from 1998 to 2007 in
      Ria de Aveiro (NW Portugal) to evaluate the effectiveness of recent legislation
      applied to reduce TBT environmental levels. H. ulvae imposex levels did not
      decrease in this estuarine system during the last decade despite the
      implementation of the EU Regulation No. 782/2003. Instead, there was a global
      significant increase in the percentage of females affected by imposex and a
      slight increase of the vas deferens sequence index (VDSI), contrasting with what
      has been described for other bioindicators in the same study area. These results
      show that different biology/ecology traits determine distinct routes of TBT
      uptake and/or bioaccumulation, pointing the importance of choosing the
      bioindicator depending on the compartment that is being monitored (sediment vs.
      water). Sediment ingestion as feeding habit is discussed and pointed as a reason
      to choose H. ulvae as a bioindicator of TBT pollution persistence in sediment. It
      is therefore predicted that the response of different prosobranch species around
      the world may diverge according to the compartment that is being monitored and
      that female masculinisation may not be completely eradicated in the near future
      due to TBT persistence in sediments.

PMID- 20145894
TI  - Investigation of perfluorinated compounds (PFCs) in mollusks from coastal waters
      in the Bohai Sea of China.
AB  - The occurrence of perfluorinated compounds (PFCs) in the Bohai Sea region, a semi
      enclosed bay in north China, was assessed in this present study. Nine different
      PFCs were measured in eleven mollusk species (soft tissues) collected from 9
      coastal cities. Most of the analyzed PFCs could be detected in the samples, with
      perfluorooctanoic acid (PFOA) as the prominent PFC, although perfluorooctane
      sulfonate (PFOS) has been shown to be more bioaccumulative than PFOA by other
      studies. The detection frequency of PFOA was 72%. Significantly high levels of
      PFOA were found in Mactra veneriformis, Scapharca subcrenata and Meretrix
      meretrix Linnaeus, with mean concentrations at 31.3 ng g(-1), 15.0 ng g(-1) and
      12.2 ng g(-1), respectively (dry weight). The distinct distribution of PFOA in
      these species can be used as a potential indicator of the bioaccumulation
      capacity. PFOS was found in mollusks at lower concentrations and frequency (61%).
      Positive linear regressions were found between perfluoroheptanoic acid (PFHpA),
      PFOA and PFOS (p < 0.01, n = 123), suggesting that these compounds may come from
      a similar origin of exposure and accumulation. It is suspected that higher
      emissions from usage or production of PFC related products might exist in
      Shouguang City, since the majority of the elevated concentrations of PFOA or PFOS
      were found in Shouguang. As the PFC concentrations in mollusks were comparatively
      low, humans are not likely to be at risk of PFC exposure through the daily
      consumption of these seafoods.

PMID- 20145895
TI  - Time location analysis for exposure assessment studies of indoor workers based on
      active RFID technology.
AB  - In this article, we describe the development of a radio frequency identification
      exposure monitoring system (RFEMS) suitable for tracking and identifying workers'
      locations in indoor workplaces. Five workers in southern Taiwan wore the RFEMS
      integrated into their equipment vests. Location and exposure data were
      transferred to data analysis software for visualization and tabular analysis in
      real-time. Data were grouped into seven task activity location categories to
      determine the time spent and percentage reception in each location. The RFEMS
      could also synchronously indicate the surrounding conditions using various
      sensors. Additional experiments were focused on locating of boundaries and
      determining the instrument stability, power sustainability, and reception
      efficiency in typical environments. The RFEMS instruments provided adequate range
      for locating (typically ca. 6-45 m in each zone), allowing us to locate subjects
      within distinct microenvironments and to distinguish between the activities of a
      variety of workers, the average time activity pattern (TAP) recording deviation
      for both human observations and RFEMS was ca. 0.21-1.57%. Power consumption
      experiments revealed that the system could be sustained for more than 124 h. A
      pilot field test indicated that the RFEMS offers a new level of accuracy for
      direct quantification of time activity patterns in exposure assessments of indoor
      workers over long periods of time.

PMID- 20145896
TI  - Socioeconomic and personal behavioral factors affecting children's exposure to
      VOCs in urban areas in Korea.
AB  - Volatile organic compounds (VOCs) are known to cause adverse health effects. We
      investigated the relationships between children's VOC exposure and socioeconomic
      and human activity factors with passive personal samplers, questionnaires, and
      time-activity diaries (TAD). Statistical analyses were conducted using SAS 9.1,
      and the results were organized using SigmaPlot 8.0 software. Chemicals such as
      benzene, toluene, 2-butanone, ethylbenzene, xylene, chloroform, n-hexane,
      heptane, and some kinds of decanes, which are known to adversely affect public
      health, were identified in measured samples. These were mainly emitted from
      outdoor sources (e.g., vehicular traffic) or indoor sources (e.g., household
      activities such as cooking and cleaning) or both. We concluded that region was
      the most important socioeconomic factor affecting children's VOC exposure, and
      the significant compounds were n-hexane (p = 0.006), 1,1,1-trichloroethane (p =
      0.001), benzene (p = 0.003), toluene (p = 0.002), ethylbenzene (p = 0.020), m-, p
      xylene (p = 0.014), dodecane (p = 0.003), and hexadecane (p = 0.001). Parental
      education, year of home construction and type of housing were also slightly
      correlated with personal VOC exposure. Only the concentration of o-xylene (p =
      0.027) was significantly affected by the parental education, and the
      concentrations of benzene (p = 0.030) and 2-butanone (p = 0.049) by the type of
      housing. Also, tridecane (p = 0.049) and n-hexane (p = 0.033) were significantly
      associated with the year of home construction. When household activities such as
      cooking were performed indoors, children's VOC concentrations tended to be
      higher, especially for n-hexane, chloroform, heptane, toluene (p < 0.05), 1,1,1
      trichloroethane, benzene, dodecane, and hexadecane (p < 0.01). However, smoking
      had a significant effect for only dodecane, and cleaning had no impact on any VOC
      concentrations. Considering both socioeconomic and personal behavioral factors
      simultaneously, socioeconomic factors such as region had a greater effect on
      children's VOC exposures than indoor activities. From this study, we can suggest
      that socioeconomic factors as well as environmental factors should be considered
      when formulating environmental policy to protect children's health.

PMID- 20145897
TI  - Assessment of air pollution genotoxicity by molecular markers in the exposed
      samples of Pseudevernia furfuracea (L.) Zopf in the province of Kayseri (Central
      Anatolia).
AB  - In living organisms heterogenous air pollutants are considered as a major source
      of DNA damage. In this study, we aimed to describe the DNA changes in
      Pseudevernia furfuracea (L.) Zopf samples exposed to pollution at various sites
      in Kayseri by RAPD (random amplified polymorphic DNA) analysis in order to reveal
      the pattern of genetic variation influenced by the environmental pollution. The
      study area is characterized by the presence of numerous industrial activities,
      such as steel works, glassworks, shipbuilding, and metallurgical, mechanical,
      chemical and food industries. Control samples were collected from Cat forest
      (Sivas) and exposed to pollution in dry and wet seasons in the province of
      Kayseri located in Central Anatolia. Results indicated that heterogeneous
      pollutants might have contributed to the changes in the band patterns obtained by
      RAPD analysis, reflecting the occurrence of DNA damage in the control samples.

PMID- 20145898
TI  - Frequency analysis of air quality time series for traffic related pollutants.
AB  - In the present work, annual time series of traffic related pollutants (CO and
      PM(10)) were considered for frequency analysis (Fourier series) with the aim to
      understand the underlying physical processes and the influence of emission
      sources on the variability of the air pollutant concentrations. Several urban
      traffic and suburban background air quality stations located in Porto
      metropolitan area (Portugal) were analysed. The results obtained for CO and
      PM(10) reveal the important contributions of short-term fluctuations (12 h and 24
      h periods). However, the spectrum signals at low frequencies are significantly
      different between these pollutants thus stressing that temporal variations of CO
      and PM(10) are influenced by different processes. Cross-spectrum analysis of the
      air quality time series against wind measurements and traffic counts allowed us
      to identify the contribution of long-range transport over a period of about 21
      days to the PM(10) fluctuations. Also, a correlation of over 80% between the
      pollution levels in the vicinity of traffic sources and suburban background
      levels are found for these harmonic components in the PM(10) spectrum, while
      correlations for CO is below a significant level. Thus, the spectrum and cross
      spectrum analysis performed in this study reveal the distinct influence of local
      traffic emissions and long-range transport to CO and PM(10) fluctuations in the
      polluted urban area. The methodology shows to be a powerful tool for the analysis
      of the causes of air pollution.

PMID- 20145901
TI  - [Abdominal wall closure by incisional hernia and herniation after laparostoma].
AB  - As hernias and abdominal wall defects have a variety of etiologies each with its
      own complications and comorbidities in various constellations, efficient
      treatment requires patient-oriented management. There is no recommended standard
      treatment and the very different clinical pictures demand an individualized
      interdisciplinary approach. Particularly in the case of complicated hernias, the
      planning of the operation should focus on the problems posed by the individual
      patient. Treatment mainly depends on the etiology of the hernia, immediate or
      long-term complications and the efficiency of individual repair techniques.
      Abdominal wall repair for recurrent herniation requires direct closure of the
      fascia generally using the sublay technique with a lightweight mesh. It is still
      unclear whether persistent inflammation, mesh dislocation, fistula formation or
      other long-term complications are due to certain materials or to the surgical
      technique. With mesh infections it has been shown to be advantageous to remove a
      polytetrafluoroethylene (PTFE) mesh, while the combination of systemic and local
      treatment appears to suffice for a polypropylene or polyester mesh. Heavier
      meshes in the sublay position or plastic reconstruction with autologous tissue
      are indicated as substitutes for the abdominal wall for giant hernias, repeated
      recurrences and large abdominal wall defects. A laparostoma is increasingly more
      often created to treat septic intra-abdominal processes but is very often
      responsible for a complicated hernia. If primary repair of the abdominal wall is
      not an option, resorbable material or split skin is used for coverage under the
      auspices of a planned hernia repair.

PMID- 20145902
TI  - [Skin cancer in organ transplant patients. Epidemiology and management].
AB  - Transplant recipients are at significantly increased risk of cancer development
      as a long term complication. Skin cancer is the most common cancer, representing
      40-50% of post transplant malignancies. In the first 10 years post
      transplantation, some 15%-40% of patients develop skin cancer, primarily squamous
      cell carcinoma and basal cell carcinoma, but also melanoma, Merkel cell carcinoma
      and virally-induced Kaposi sarcoma. The management of skin cancer includes
      secondary prophylaxis and address attention to areas of widespread actinic
      damage, usually with topical agents. In high risk skin cancer or metastatic
      disease a substantial reduction in immunosuppression to switching to mTOR
      inhibitors appears to substantially improve the prognosis. The management of the
      individual tumor types is discussed; in general it follows the current
      guidelines.

PMID- 20145903
TI  - [Immunosuppressive therapy after transplantation. Dermatologic relevance and
      pathomechanisms].
AB  - Immunosuppressive therapy keeps rejection in check following solid organ
      transplantation. Drug reactions, inflammatory and infectious skin conditions
      frequently follow. Specific side effects can be avoided by switching individual
      agents. In addition to UV light, immunosuppressants are the most important driver
      for squamous cell carcinoma of the skin (SCC). Beyond immunosuppression,
      cyclosporine A promotes carcinogenesis by TGF beta and VEGF, while mTOR
      inhibitors are antiproliferative. Azathioprine photosensitizes to UVA and enables
      UVA to damage DNA directly. To fight skin cancer, global reduction of
      immunosuppression is the most effective measure. Switching calcineurin inhibitors
      to mTOR inhibitors is probably to be recommended, while omitting azathioprine may
      potentially be advisable in recurrent SCC.

PMID- 20145904
TI  - Detection of quantitative trait loci controlling pre-harvest sprouting resistance
      by using backcrossed populations of japonica rice cultivars.
AB  - Backcrossed inbred lines (BILs) and a set of reciprocal chromosome segment
      substitution lines (CSSLs) derived from crosses between japonica rice cultivars
      Nipponbare and Koshihikari were used to detect quantitative trait loci (QTLs) for
      pre-harvest sprouting resistance. In the BILs, we detected one QTL on chromosome
      3 and one QTL on chromosome 12. The QTL on the short arm of chromosome 3
      accounted for 45.0% of the phenotypic variance and the Nipponbare allele of the
      QTL increased germination percentage by 21.3%. In the CSSLs, we detected seven
      QTLs, which were located on chromosomes 2, 3 (two), 5, 8 and 11 (two). All
      Nipponbare alleles of the QTLs were associated with an increased rate of
      germination. The major QTL for pre-harvest sprouting resistance on the short arm
      of chromosome 3 was localized to a 474-kbp region in the Nipponbare genome by the
      SSR markers RM14240 and RM14275 by using 11 substitution lines to replace the
      different short chromosome segments on chromosome 3. This QTL co-localized with
      the low-temperature germinability gene qLTG3-1. The level of germinability under
      low temperature strongly correlated with the level of pre-harvest sprouting
      resistance in the substitution lines. Sequence analyses revealed a novel
      functional allele of qLTG3-1 in Nipponbare and a loss-of-function allele in
      Koshihikari. The allelic difference in qLTG3-1 between Nipponbare and Koshihikari
      is likely to be associated with differences in both pre-harvest sprouting
      resistance and low-temperature germinability.

PMID- 20145905
TI  - Development of a wheat genotype combining the recessive crossability alleles
      kr1kr1kr2kr2 and the 1BL.1RS translocation, for the rapid enrichment of 1RS with
      new allelic variation.
AB  - The main objective of the present work was to develop a wheat genotype containing
      both the recessive crossability alleles (kr1kr1kr2kr2), allowing high
      crossability between 6x wheat and diploid rye, and the 1BL.1RS wheat/rye
      translocation chromosome. This wheat genotype could be used as a recipient
      partner in wheat-rye crosses for the efficient introduction of new allelic
      variation into 1RS in translocation wheats. After crossing the wheat cultivars
      'Mv Magdalena' and 'Mv Beres', which carry the 1BL.1RS translocation involving
      the 1RS chromosome arm from 'Petkus', with the line 'Mv9 kr1', 117 F(2) plants
      were analysed for crossability, ten of which had higher than 50% seed set with
      rye and thus presumably carried the kr1kr1kr2kr2 alleles. Four of the ten plants
      contained the 1BL.1RS translocation in the disomic condition as detected by
      genomic in situ hybridization (GISH). The wheat x rye F(1) hybrids produced
      between these lines and the rye cultivar 'Kriszta' were analysed in meiosis using
      GISH. 1BL.1RS/1R chromosome pairing was detected in 62.4% of the pollen mother
      cells. The use of fluorescent in situ hybridization (FISH) with the repetitive
      DNA probes pSc119.2, Afa family and pTa71 allowed the 1R and 1BL.1RS chromosomes
      to be identified. The presence of the 1RS arm from 'Kriszta' besides that of
      'Petkus' was demonstrated in the F(1) hybrids using the rye SSR markers RMS13 and
      SCM9. In four of the 22 BC(1) progenies analysed, only 'Kriszta'-specific bands
      were observed with these markers, though the presence of the 1BL.1RS
      translocation was detected using GISH. It can be concluded that recombination
      occurred between the 'Petkus' and 'Kriszta' 1RS chromosome arms in the
      translocated chromosome in these plants.

PMID- 20145906
TI  - Suicides by country of birth groupings in England and Wales: age-associated
      trends and standardised mortality ratios.
AB  - INTRODUCTION: Suicide rates in England and Wales have declined in recent years. A
      better understanding of age-associated trends in different ethnic groups may
      inform strategies to sustain this decline. MATERIALS AND METHODS: This study
      examines suicide rates and age-associated trends in England and Wales by country
      of birth (used as a proxy for ethnicity) using the latest available national
      mortality data. RESULTS: The main findings were (a) suicide rates were generally
      higher in males than females in all age bands in all country of birth groups
      except the China group, where suicides rates were higher in females than males in
      the older age bands; (b) male suicide rates increased with ageing in the Indian
      sub-continent group and female suicide rates increased with ageing in the Africa
      and China groups; (c) male standardised mortality ratios (SMRs) were generally
      higher in the younger age bands in the Eastern Europe and Caribbean groups and
      generally lower in the Australasian, Middle East and Western Europe groups; (d)
      male SMRs were generally higher in the older age bands in Eastern Europe,
      Caribbean, Australasian and Western Europe groups and lower in all age bands in
      the Indian sub-continent group, and (e) female SMRs were generally higher in the
      older age bands in the China, Africa and Caribbean groups. CONCLUSION: There is a
      need for epidemiological data on suicides in BME groups, including age-associated
      trends, trends over time, risk and protective factors and methods of suicide to
      inform suicide prevention strategies.

PMID- 20145908
TI  - [The spinal intervertebral disc].
AB  - The spinal intervertebral disc can cause neurocompression or pain as a result of
      degeneration. Surgical interventions, therefore, include decompression, fusion,
      disc replacement or a combination thereof. Identifying the painful segment in the
      case of axial pain requires accurate segment diagnosis and may require invasive
      diagnostic measures (joint infiltration, discography), since imaging is often not
      fluid enough. In the case of fusion following disc removal, the placeholder is
      substitued in the form of a cage or autologous iliac crest graft. Alternatively,
      when dorsal elements are intact, a disc prosthesis can be inserted. In the case
      of compression, removal of the compromised structures (disc, osteophytes) becomes
      necessary. If the indication is correctly made and the appropriate surgical
      technique used, good results can be expected from cervical spine surgery.

PMID- 20145907
TI  - Factors associated with reported childhood depressive symptoms at age 8 and later
      self-reported depressive symptoms among boys at age 18.
AB  - AIMS: This study aimed to study conditions associated with depressive symptoms at
      ages 8 and 18 in a representative birth cohort of Finnish males. METHODS: The
      participants in this community-based 10-year follow-up study consisted of 2,348
      boys born in 1981. At age 8, three informant sources were used: parents,
      teachers, and the children themselves. Depressive symptoms were established using
      the Children's Depression Inventory (CDI). At age 18, self-report questionnaires
      were used to study the boys' family factors, life events, adaptive functioning,
      and substance use. Depressive symptoms at age 18 were established using Beck's
      Depression Inventory (BDI). RESULTS: Poor adaptive functioning at age 18 was
      independently associated with both child and late adolescent depressive symptoms.
      Use of illicit drugs and somatic health problems were independently associated
      with later depressive symptoms. Parental divorce in early childhood independently
      predicted depressive symptoms both in childhood and in late adolescence. Teacher
      reports of child's total problems at age 8 independently predicted depressive
      symptoms at age 18. CONCLUSIONS: Depression in males at ages 8 and 18 is
      particularly associated with stressful life events in childhood, whereas late
      depression is associated with somatic health problems and substance use. Further
      population-based studies comparing conditions associated with childhood and
      adolescent depression are needed.

PMID- 20145909
TI  - Subcutaneous glucose measurements and glucose regulation (?).

PMID- 20145910
TI  - Analysis of licking microstructure provides no evidence for a reduction in reward
      value following acute or sub-chronic phencyclidine administration.
AB  - RATIONALE: The N-methyl D-aspartate antagonist phencyclidine (PCP) is purported
      to mimic the negative, cognitive and positive symptoms of schizophrenia. Thus,
      acute and sub-chronic PCP treatment in rodents might produce anhedonia, a
      decrease in the pleasure produced by rewards. OBJECTIVES: Experiment 1
      investigated whether acute PCP treatment changes the value of sucrose. A
      comparison was made to (+)MK-801, a drug often used interchangeably with PCP in
      preclinical studies. Experiment 2 assessed the effects of withdrawal from sub
      chronic PCP treatment on the value of sucrose. METHODS: Experiment 1 examined the
      dose-response effects of PCP and (+)MK-801 on licking microstructure during
      sucrose consumption. Experiment 2 assessed the effects of withdrawal from sub
      chronic PCP treatment (5 mg/kg twice daily for 7 days), on licking microstructure
      during sucrose consumption. Locomotor activity testing was carried out in
      experiment 2 to confirm the sensitisation effect of the PCP regimen on
      amphetamine-induced hyperlocomotion. RESULTS: Low to moderate acute doses of PCP
      and (+)MK-801 increased the amount of sucrose consumed. Higher doses decreased
      consumption and the number of licks per cluster (cluster size) but also increased
      the average inter-lick interval, which may indicate motor impairment. There was
      no evidence that withdrawal from sub-chronic PCP treatment produced decreases in
      consumption or lick cluster size. CONCLUSIONS: Following acute PCP treatment, we
      found no evidence of reduced reward value without the presence of confounding
      motor deficits. Sub-chronic PCP withdrawal also produced no decrease in reward
      value. Therefore, the current results indicate that neither acute PCP treatment
      nor sub-chronic PCP withdrawal produce consummatory anhedonia.

PMID- 20145912
TI  - Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in
      meconium from newborns for detection of alcohol abuse in a maternal health
      evaluation study.
AB  - Fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) were determined in 602
      meconium samples in a maternal health evaluation study for detection of
      gestational alcohol consumption. A validated headspace solid phase
      microextraction method in combination with GC-MS was used for FAEE and the
      cumulative concentration of ethyl palmitate, ethyl linoleate, ethyl oleate, and
      ethyl stearate with a cut-off of 500 ng/g was applied for interpretation. A new
      and simple method was developed and validated for quantification of EtG from 10
      20 mg meconium with D(5)-EtG as internal standard consisting of 30 min.
      extraction with methanol/water (1:1, v/v), evaporation of methanol, filtration of
      the aqueous solution through a cellulose filter and injection into LC-MS-MS. The
      limits of detection and quantification for EtG were 10 and 30 ng/g, the recovery
      86.6 to 106.4% and the standard deviation of the concentrations ranged from 13%
      at 37 ng/g to 5% at 46,700 ng/g (N = 6). FAEE above the cut-off were found in 43
      cases (7.1%) with cumulative concentrations between 507 and 22,580 ng/g and with
      one outlier of about 150,000 ng/g (EtG not detected). EtG was detected in 97
      cases (16.3%) and concentrations between LOD and 10,200 ng/g with another outlier
      of 82,000 ng/g (FAEE 10,500 ng/g). Optimal agreement between the two markers was
      obtained with a cut-off for EtG of 274 ng/g and 547 cases with both FAEE- and EtG
      negative, 33 cases with both FAEE- and EtG-positive, nine cases with FAEE
      positive and EtG-negative, and seven cases with FAEE-negative and EtG-positive.
      Differences in physical, chemical, and biochemical properties and in the
      pharmacokinetic behavior are discussed as reasons for the deviating cases. In
      none of the 602 cases, serious alcohol consumption was reported by the mothers
      and no evidence for gestational ethanol exposure was observed in the medical
      investigation of the newborns. It is concluded that the combined use of FAEE and
      EtG in meconium as markers for fetal alcohol exposure essentially increases the
      accuracy of the interpretation and helps to avoid false positive and false
      negative results.

PMID- 20145913
TI  - Validated assay for studying activity profiles of human liver UGTs after drug
      exposure: inhibition and induction studies.
AB  - UDP-glucuronsyltransferases (UGTs) are a family of conjugating enzymes that
      participate in the metabolism of many drugs. The study of potential drug-drug
      interactions involving UGTs has been largely hindered by the limited availability
      of selective functional assays for individual UGT enzymes. We propose a sensitive
      and reproducible procedure for the activity measurements of four major human
      hepatic UGT forms. The assays are based on analysis and quantification by high
      performance liquid chromatography-tandem mass spectrometry of glucuronides formed
      from selective probe substrates, namely, beta-estradiol (UGT1A1, 3-glucuronide),
      1-naphthol (UGT1A6), propofol (UGT1A9), and naloxone (UGT2B7). The analytical
      methods developed in the present study have been validated under good laboratory
      practice compliance following FDA recommendations. The assays can be easily
      applied to both phenotyping UGT reactions in liver-derived cellular and
      subcellular systems, and drug-drug interaction in vitro studies. Chemical
      inhibition of UGTs was tested in human liver microsomes at substrate
      concentrations lower than the corresponding K (M) values. Under these conditions,
      selective inhibition of UGT2B7 by fluconazole and low amitriptyline
      concentrations were observed, whereas diclofenac and quinidine were shown as non
      enzyme-selective inhibitors of UGTs. Induction of UGTs was studied in primary
      human hepatocytes and HepG2 cells cultured in 96-well plates. Aryl hydrocarbon
      receptor ligands (except indirubin in hepatocytes) increased the UGT1A1 activity
      in both cell models. The highest effects were observed in HepG2 cells exposed to
      indirubin (21-fold over the control) and omeprazole or beta-naphthoflavone (about
      sixfold). Although variable effects were observed in other UGT enzymes, the
      degree of induction was generally lower than that for UGT1A1.

PMID- 20145914
TI  - Intravascular tissue reactions induced by various types of bioabsorbable
      polymeric materials: correlation between the degradation profiles and
      corresponding tissue reactions.
AB  - INTRODUCTION: Several different bioabsorbable polymeric coil materials are
      currently used with the goal of improving treatment outcomes of endovascular
      embolization of intracranial aneurysms. However, little is known about the
      correlation between polymer degradation profiles and concomitant tissue responses
      in a blood vessel. The authors describe in vitro degradation characteristics of
      nine different polymeric materials and their corresponding tissue responses
      induced in rabbit carotid arteries. METHODS: Mass loss and molecular weight loss
      of nine commercially available bioabsorbable sutures were evaluated in vitro up
      to16 weeks. The same nine materials, as well as platinum coils, were implanted
      into blind-end carotid arteries (n = 44) in rabbits, and their tissue reactions
      were evaluated histologically 14 days after the implantation. RESULTS: Five of
      the nine polymers elicited moderate to strong tissue reactions relative to the
      remaining materials. While polymer mass loss did not correlate with their
      histologic findings, polymers that showed a faster rate of molecular weight loss
      had a tendency to present more active tissue reactions such as strong
      fibrocellular response around the implanted material with a moderate inflammatory
      cell infiltration. Maxon exhibited the fastest rate of molecular weight loss and
      poly-l-lactic acid the slowest. CONCLUSIONS: The rate of molecular weight loss
      may be an important factor that is associated with the degree of bioactivity when
      bioabsorbable polymers are implanted into blood vessels. For further quantitative
      analysis, additional experiments utilizing established aneurysm models need to be
      conducted.

PMID- 20145915
TI  - HLA class I and class II HLA DRB profiles in Egyptian children with rheumatic
      valvular disease.
AB  - Poststreptococcal sequelae, especially acute rheumatic fever/rheumatic heart
      disease continues to occur in significant proportions in many parts of the world,
      especially in less developed countries. An important factor in the study of
      rheumatic heart disease is the human genetic susceptibility to the disease. The
      aim of the present study was to detect the most prevalent HLA class I and class
      II types associated with risk of rheumatic heart disease in Egyptian children.
      Our study was performed on 100 patients with rheumatic valvular heart diseases
      and 71 control subjects. Patients were recruited from the Heart Institute,
      Embaba, Egypt. HLA typing for HLA class I was performed by serotyping and HLDR
      allele genotyping was performed using INNO-LiPA kits. In the study of HLA class
      I, there was a statistically significant increase in the B5 allele (P = 0.03;
      odds ratio, 3.46 [1.12-10.72]) in patients compared to controls, while B49 and
      B52 alleles (P = 0.004 and P = 0.02) were found in controls only. There was a
      statistically significant increase in HLA DR* 04-02, 3.46 (1.12-10.72) and HLA DR
      *10-0101 5.75 (1.27-25.98) in patients. Meanwhile HLA DR*1309120 was found only
      in controls (P = 0.02). Our study provides further information on the genetic
      predisposition for rheumatic valvular disease and the protective genotypes in
      rheumatic heart disease. Further insight into the molecular mechanisms of the
      disease will be a useful tool for predicting clinical outcome in those patients
      and, thus, potentially offer new means and approaches to treatment and
      prophylaxis, including a potential vaccine.

PMID- 20145916
TI  - Outcome predictors of pediatric extracorporeal cardiopulmonary resuscitation.
AB  - Extracorporeal cardiopulmonary resuscitation (ECPR) allows clinicians to
      potentially rescue pediatric patients unresponsive to traditional cardiopulmonary
      resuscitation (CPR). Clinical and laboratory variables predictive of survival to
      hospital discharge are beginning to emerge. In this retrospective, historical
      cohort case series, clinical, and laboratory data from 31 pediatric patients (<21
      years of age) receiving ECPR from March 2000 to April 2006 at our university
      affiliated, tertiary-care children's hospital were statistically analyzed in an
      attempt to identify variables predictive of survival to hospital discharge. Seven
      patients survived to hospital discharge (23%), and 24 patients died. Survival was
      independent of gender, age, and CPR duration. ECPR survival was, however,
      associated with a lower pre-ECPR phosphorus concentration (P = 0.002) and a lower
      pre-ECPR creatinine concentration (P = 0.05). A classification tree analysis,
      using, in part, a pre-ECPR phosphorus concentration threshold and a CPR ABG base
      excess concentration threshold, yielded a 96% nominal accuracy of predicting
      survival to hospital discharge or death. A large, multicenter, prospective cohort
      study aimed at validating these predictive variables is needed to guide
      appropriate ECPR patient selection. This study reveals the potential survival
      benefit of ECPR for pediatric patients, regardless of CPR duration prior to ECPR
      cannulation.

PMID- 20145917
TI  - Pulmonary artery diverticulum: an angiographic marker for Williams syndrome.
AB  - We evaluated the presence of pulmonary artery diverticulum in patients with
      Williams syndrome in comparison with other conditions causing peripheral
      pulmonary artery stenosis (PPS). Angiographic characteristics of patients with a
      definitive diagnosis of Williams syndrome, by fluorescence in situ hybridization,
      between 1990 and 2008 were reviewed. These data were compared with those
      diagnosed with those for patients with PPS without Williams syndrome.
      Differentiating morphological features on angiography were compared between the
      groups, along with demographic and echocardiographic data. Twelve patients with a
      chromosomal diagnosis of Williams syndrome who underwent cardiac catheterization
      were identified. Seven were male. Eleven patients (91%) had supravalvar aortic
      stenosis and nine (81%) had PPS. Pulmonary valve stenosis was seen in two
      patients. Eight patients who were negative for Williams syndrome and had PPS were
      identified during the same period. Two had Alagille syndrome and one had Noonan
      syndrome. Mean age at catheterization was 5 years in the Williams group versus 8
      years in the non-Williams group. Pulmonary artery diverticulum involving the main
      pulmonary artery was documented in all patients with Williams syndrome, while
      none of the patients in the other group had it. It originated at the bifurcation
      of the pulmonary artery in all. In conclusion, the angiographic appearance of a
      diverticulum as an extension of the main pulmonary artery is a consistent finding
      in patients with Williams syndrome. Compared to the classically described
      findings of supravalvar aortic stenosis or PPS, pulmonary artery diverticulum can
      be considered as a pathognomonic feature of Williams syndrome.

PMID- 20145918
TI  - Renal artery aneurysm in a hypertensive child treated by percutaneous coil
      embolization.
AB  - A 16-year-old boy was admitted to our hospital with uncontrolled hypertension. A
      left renal artery aneurysm was detected on colour Doppler US and CT. Renal
      arteriography demonstrated the aneurysm and focal renal parenchymal areas of
      decreased perfusion. The renal artery aneurysm was successfully treated by
      transcatheter coil embolization.

PMID- 20145919
TI  - Pectus deformities: tomographic analysis and clinical correlation.
AB  - OBJECTIVE: To assess, with computed tomography (CT) studies, features of anterior
      chest wall development that can be related to different types of pectus
      deformities. MATERIALS AND METHODS: From 71 patients with pectus deformities and
      chest coronal CT scans, 48 (40 male and 8 female), with a mean age of 15.8 years
      (ranging from 5 years to 38.4 years) were selected and divided into five groups,
      according to clinical type of deformity and image quality. A similar CT study was
      performed in a sixth group of 14 individuals with no underlying pectus deformity
      (control group), six male and eight female, mean age 19.3 years, (range 10.8
      years to 30.5 years), totaling 62 subjects. Tomographic studies were performed on
      a 64-section CT scanner, with parameters varied according to the subject's body
      mass index (BMI). Coronal reconstructions were used to assess six features of the
      sternum and costal cartilages in the groups. Two other factors, a sternal index,
      created to estimate the sternal body width, and the sternocostal angles, were
      also studied. RESULTS: Feature I was noted in 13 patients and in no controls (P =
      0.002), feature II in 39 patients and in one control (P = 0.000), feature III in
      37 patients and in two controls (P = 0.002), and feature IV in two patients and
      in no controls (P = 0.002). The sternal index was significant to one group of
      patients. CONCLUSION: The features studied and the index provide measurable and
      applicable data for the interpretation of anterior chest wall tomography, with
      possible implications for prognosis and treatment of different types of pectus
      deformities.

PMID- 20145920
TI  - Hybrid versus fusion imaging: are we moving forward judiciously?

PMID- 20145921
TI  - SPECT neuroimaging and neuropsychological functions in different stages of
      Parkinson's disease.
AB  - PURPOSE: The present study investigated differences and associations between
      cortical perfusion, nigrostriatal dopamine pathway and neuropsychological
      functions in different stages of Parkinson's disease (PD). METHODS: We recruited
      53 non-demented PD patients divided into four groups according to the Hoehn and
      Yahr (HY) staging system and 20 healthy controls who were used in the comparison
      of the neuropsychological findings. Each patient underwent two separate brain
      single photon emission computed tomography (SPECT) studies (perfusion and
      dopamine transporter binding) as well as neuropsychological evaluation. Perfusion
      images of each patient were quantified and compared with a normative database
      provided by the NeuroGam software manufacturers. Mean values obtained from the
      cortical areas and neuropsychological measures in the different groups were also
      compared by analysis of covariance (ANCOVA) controlling for disease duration and
      educational level. RESULTS: We found cognitive deficits especially in the late PD
      stages (HY 3, 4 and 5) compared to the early stages (HY 1 and 2) and associations
      between cognitive decrements and cortical perfusion deterioration mainly in the
      frontal and posterior cortical areas. Compared with controls, PD patients showed
      impairments of cognition and cerebral perfusion that increased with clinical
      severity. Furthermore, we found a significant correlation between the performance
      on the phonemic fluency task and regional cerebral blood flow (rCBF) in the left
      frontal lobe. Dopamine transporter binding in the left caudate nucleus
      significantly correlated with blood flow in the left dorsolateral prefrontal
      cortex (DLPFC), but not with measures of executive functions. CONCLUSION: There
      are significant cognitive and perfusion deficits associated with PD progression,
      implying a multifactorial neurodegeneration process apart from dopamine depletion
      in the substantia nigra pars compacta (SNc).

PMID- 20145922
TI  - Recent changes in the riparian forest of a large regulated Mediterranean river:
      implications for management.
AB  - The structure of the floodplain forests of the Middle Ebro River (NE Spain) was
      examined at patch and landscape scales along a three-step chronosequence defined
      according to the extent of flow regulation-induced hydrogeomorphic changes, with
      the ultimate purpose of producing baseline information to guide through
      management and restoration plans. At patch scale, a total of 6,891 stems within
      39 plots were registered for species, diameter and health status. The stem
      density, size class distribution, canopy dieback and mortality were further
      compared by means of non-parametric tests. At landscape scale, the temporal
      evolution of the area occupied by forest stands of different ages in the
      floodplain along the chronosequence was evaluated using four sets of aerial
      photographs dated in 1927, 1957, 1981 and 2003. The within-patch structure of
      pioneer forests (<25-30 years old) was characterized by dense and healthy
      populations of pioneer species (Populus nigra, Salix alba and Tamarix spp.), but
      the area occupied by these forest types has progressively decreased (up to 37%)
      since the intensification of river regulation (ca. 1957). In contrast, non
      pioneer forests (>25-30 years old) were characterized by declining and sparse P.
      nigra-S. alba-Tamarix spp. stands, where late-seral species such as Ulmus minor
      and Fraxinus angustifolia were frequent, but only as small-size stems. At
      landscape scale, these type of senescent forests have doubled their surface after
      river regulation was intensified. Populus alba only appeared in the oldest plots
      recorded (colonized before 1957), suggesting sexual regeneration failure during
      the last five decades, but usually as healthy and dense stands. Based on these
      findings, measures principally aimed at recovering some hydrogeomorphic dynamism
      are recommended to guarantee the self-sustainability of the floodplain forest
      ecosystem.

PMID- 20145923
TI  - Palliative resection in noncurative gastric cancer patients.
AB  - BACKGROUND: Palliative resection for noncurable gastric cancer remains
      controversial, especially in the elderly. This retrospective study was designed
      to elucidate the clinicopathological factors and operative outcome in patients
      undergoing palliative gastric resection. METHODS: From January 1988 to December
      2008, 365 patients received palliative gastrectomy while 151 underwent
      exploratory laparotomy or gastrojejunostomy for noncurative gastric cancer at the
      Department of Surgery, Taipei Veterans General Hospital. Among the 365 patients,
      182 patients (Group A) were aged 70 or less and 183 patients (Group B) were older
      than 70 years of age. Clinicopathological characteristics and surgical morbidity
      and mortality were analyzed. RESULTS: The overall survival of patients who
      underwent resection was 10.2 months and that of patients without resection 4.48
      months (p < 0.001). Compared to Group B, Group A patients were predominantly
      female (p < 0.001), had more advanced Borrmann-type tumors (p = 0.004), more
      diffuse type of Lauren classification (p < 0.001), and poorer cell
      differentiation (p < 0.001). The median overall survival was 10.5 months in Group
      A and 9.7 months in Group B (p = 0.854). The surgical morbidity was significant
      higher if the patients had comorbidity (p = 0.028). Both surgical morbidity
      (13.8% vs. 26.8%, p = 0.028) and mortality (0.5% vs. 6.0%, p < 0.0001) were
      significantly higher in Group B. CONCLUSIONS: Gastric cancer is less aggressive
      in the elderly. Palliative gastrectomy can be performed in both younger and older
      patients, but younger patients tolerate surgery better. More attention should be
      paid to the perioperative care of the elderly.

PMID- 20145924
TI  - Different sites and prognoses of gastrointestinal stromal tumors of the stomach:
      report of 187 cases.
AB  - BACKGROUND: The stomach is the most common site of gastrointestinal stromal
      tumors (GISTs), but the clinical behavior of gastric GISTs at different sites is
      unclear. This study was designed to evaluate the clinicopathological (CP)
      parameters and influence of different gastric sites on outcome in patients with
      GIST. METHODS: The CP and follow-up records of 187 patients with GIST who were
      treated at TianJin Medical University Cancer Institute & Hospital between January
      1985 and December 2006 were reviewed. There were 97 men and 90 women (aged 17-88
      (median, 56.5) years). CP factors were assessed for overall survival (OS) by
      using univariate and multivariate analysis. RESULTS: The numbers of cases of
      upper, middle, and lower third gastric GISTs were 69 (36.9%), 103 (55.1%), and 15
      (8%), respectively. Sites of GISTs in the middle or upper stomach, tumor size,
      intermediate- or high-risk groups, high mitotic count, and low resection status
      were associated with poor OS (p = 0.041, 0.046, 0.006, 0.000, 0.000,
      respectively) in a univariate analysis. In a multivariate analysis, tumor
      location in the upper and middle third of the stomach (p = 0.035), an
      intermediate or high risk (p = 0.01), and incomplete resection status (p = 0.006)
      were predictive of poor OS. CONCLUSIONS: Patients in intermediate- and high-risk
      groups had an unfavorable outcome. A complete resection is the most important
      treatment for survival. The location of GIST in the lower third of the stomach
      may be a favorable factor, and the significance of different tumor sites for
      prognosis of gastric GISTs needs to be further clarified.

PMID- 20145925
TI  - C-reactive protein -717C>T genetic polymorphism associates with esophagectomy
      induced stress hyperglycemia.
AB  - BACKGROUND: Stress hyperglycemia refers to the transient hyperglycemia seen
      during illness and is usually restricted to patients without previous evidence of
      diabetes. The influence of genetics on surgery-induced hyperglycemia remains only
      partially understood. METHODS: The study participants were Japanese patients
      treated for thoracic esophageal cancer with curative esophagectomy at Akita
      University Hospital between 2003 and 2007. We determined the associations between
      esophagectomy-induced stress hyperglycemia (> or =30 mg/dl increases in blood
      glucose during surgery) and genetic polymorphisms for C-reactive protein (CRP),
      tumor necrosis factor (TNF)-alpha, -beta, interferon-gamma, transforming growth
      factor-beta1, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-6 receptors, IL-10, IL
      12beta, adiponectin, and peroxisome proliferator-activated receptor-gamma.
      RESULTS: In 28 (46%) patients, blood glucose levels increased more than 30 mg/dl
      during surgery. Among the genetic polymorphisms tested, CRP -717C>T was
      significantly associated with stress hyperglycemia during esophagectomy.
      Multivariate logistic regression revealed that patients with the CRP -717T/T
      genotype had a significantly greater risk of developing surgery-induced
      hyperglycemia than those with the CRP -717C/T genotype. Stress hyperglycemia was
      also significantly associated with postoperative infectious complications and
      duration of intensive care unit stay. CONCLUSIONS: It is suggested that CRP -717
      C>T genetic polymorphism may be a predictive factor for stress hyperglycemia in
      patients receiving esophagectomy for thoracic esophageal cancer.

PMID- 20145926
TI  - Risk factors for symptomatic anastomotic leakage after low anterior resection for
      rectal cancer with 30 Gy/10 f/2 w preoperative radiotherapy.
AB  - OBJECTIVE: This retrospective study was designed to analyze the risk factors for
      symptomatic leakage after low anterior resection (LAR) for patients with rectal
      cancer who received 30 Gy/10 f/2 w preoperative radiotherapy. METHODS: From April
      2002 to December 2008, a total of 223 patients with mid-low rectal cancer
      received 30 Gy/10 f/2 w preoperative radiotherapy and underwent LAR. Six patients
      were excluded for positive air test, incomplete anastomotic rings, or other major
      adverse intraoperative events. In the 217 patients with satisfactory anastomoses,
      15 probably factors relating to anastomotic leakage were recorded and
      statistically analyzed. RESULTS: The median patient age was 57 years, and 48%
      were women. The median level of anastomosis was 6 cm, median operating time was
      130 minutes, and intraoperative blood loss was 200 ml. The symptomatic leakage
      rate was 11.5% (25/217). Multivariable analysis demonstrated that male gender
      (odds ratio (OR) = 2.63; p = 0.0474), level of anastomosis < or =4 cm (OR = 8.80;
      p = 0.038), no defunctioning stoma (OR = 3.80; p = 0.038), and blood loss >200 ml
      (OR = 3.32; p = 0.080) were the independent risk factors for anastomotic leakage.
      CONCLUSIONS: For patients with rectal cancer treated with preoperative
      radiotherapy and low anterior resection, the risk factors for anastomotic leakage
      are male gender, lack of defunctioning stoma, level of anastomosis < or =4 cm,
      and blood loss >200 ml. A defunctioning stoma can decrease the occurrence of
      symptomatic anastomotic leakage and should be routinely performed in all low
      anterior resections after 30 Gy/10 f/2 w preoperative radiotherapy.

PMID- 20145927
TI  - Clinical significance of B7-H1 and B7-1 expressions in pancreatic carcinoma.
AB  - BACKGROUND: Cancer cells develop mechanisms to evade immune cells and achieve
      progression. Aberrant B7-H1 and B7-1 expressions may help pancreatic carcinoma
      (PC) cells escape immune attack; these molecules can be considered as prognostic
      markers for patients with PC who have undergone radical resection. METHODS: We
      recruited 81 patients who had undergone radical surgical resection for PC between
      1999 and 2007. To investigate the prognostic factors, we evaluated the B7-H1 and
      B7-1 protein expressions in the tissue specimens of these 81 patients by
      immunohistochemistry and analyzed the clinical and pathological features of these
      specimens. RESULTS: B7-H1 was expressed mainly in pancreatic islets, and no B7-1
      expression was detected in normal pancreatic tissues. B7-H1 and B7-1 expressions
      were higher in pancreatic carcinoma tissues than in normal pancreatic tissues (P
      < 0.05). B7-H1 and B7-1 significantly correlated with the pathological grade and
      tumor-node-metastasis (TNM) stage, respectively (P < 0.05). Furthermore, B7-1
      negative or B7-H1-positive statuses were prognostic indicators of poor disease
      specific survival (P < 0.05), but only combined B7-1/B7-H1 expression retained
      the prognostic potential after adjusting by Cox proportional hazards regression
      models (P < 0.05). CONCLUSIONS: Both B7-H1 and B7-1 are expressed in PC; these
      molecules are important markers for PC progression. Furthermore, combined B7-1/B7
      H1 expression can serve as an independent prognostic marker for PC.

PMID- 20145928
TI  - Outcome of total parathyroidectomy and autotransplantation as treatment of
      secondary and tertiary hyperparathyroidism in children and adults.
AB  - BACKGROUND: Treatment safety and effectiveness of total parathyroidectomy and
      autotransplantation for secondary and tertiary hyperparathyroidism have been
      extensively proven in adults; the evidence for children, however, is scarce.
      Children and adolescents cannot simply be seen as young adults in the case of
      chronic kidney disease and hyperparathyroidism. The aim of this retrospective
      study was therefore, to evaluate whether parathyroidectomy with forearm autograft
      is as effective and safe in children and adolescents as in adults. METHODS: A
      group of 64 adults and 8 children and adolescents treated for secondary or
      tertiary hyperparathyroidism were retrieved from our database. The outcomes were
      compared on patient demographics, operation results, and blood parameters
      consisting of parathyroid hormone (PTH) and calcium levels. Our results were
      compared with all currently available articles on parathyroidectomy in children
      with secondary or tertiary hyperparathyroidism (n = 11). RESULTS: For adults,
      preoperative mean serum calcium was 2.67 +/- 0.29 mmol/l and mean parathyroid
      hormone (PTH) level was 120 +/- 86 pmol/l. For children, preoperative mean serum
      calcium was 2.62 +/- 0.20 mmol/l and mean parathyroid hormone (PTH) level was 80
      +/- 38 pmol/l. Postoperative calcium and parathyroid hormone levels for adults
      dropped to 2.39 +/- 0.23 mmol/l and 30 +/- 53 pmol/l, respectively. Postoperative
      calcium and parathyroid hormone levels for children dropped to 2.41 +/- 0.16
      mmol/l and 26 +/- 33 pmol/l, respectively. The effectiveness of parathyroidectomy
      with autotransplantation was 75% in children and 72% in adults. Thus,
      effectiveness did not differ significantly between children and adults.
      CONCLUSIONS: Combining the results of our own study with a literature review on
      pediatric parathyroidectomy, we conclude that parathyroidectomy and forearm
      autograft is as effective a treatment for secondary and tertiary
      hyperparathyroidism in children and adolescents as it is in adults.

PMID- 20145929
TI  - Indications for routine pathologic examination of specimens removed during trauma
      operations.
AB  - BACKGROUND: Surgical specimens removed during trauma operations are routinely
      submitted for examination by pathology. This practice has not been systematically
      evaluated and the incidence of abnormal results from these examinations remains
      unknown. The objective of this study was to identify the incidence and management
      implications of abnormal findings at pathology review of trauma specimens.
      METHODS: This is a retrospective chart and pathology review of all surgical
      specimens obtained during laparotomy or thoracotomy for trauma between January 1,
      1993 and December 31, 2005. Reports were assessed for significant abnormal
      findings, including malignancy, infectious processes, and chronic inflammation.
      Additional clinical and demographic data were obtained. The main outcome measure
      was any change in management due to the pathology result. RESULTS: A total of
      1686 specimens were obtained from 1307 trauma patients. Ten patients (0.8%) were
      identified as having clinically significant abnormal findings on pathology. Six
      findings (0.5%) were evidence of malignancy. The pathology reports did not alter
      care in any patients. In all instances malignancy was known or highly suspected
      prior to specimen examination based on other diagnostic modalities or gross
      examination during surgery. Patients with an abnormal finding were significantly
      older than the patients with normal pathology reports (70.5 vs. 30.4, P <
      0.0001). CONCLUSIONS: The routine pathology review of specimens obtained during
      trauma operations did not alter patient care and should not continue. In all
      instances of abnormal pathology, preoperative imaging or gross intraoperative
      findings led to increased suspicion of occult disease. The suggestion of
      abnormalities on imaging or intraoperatively warrants pathologic examination,
      especially in older patients.

PMID- 20145930
TI  - Tumor protein p53-induced nuclear protein (TP53INP1) expression in medullary
      thyroid carcinoma: a molecular guide to the optimal extent of surgery?
AB  - BACKGROUND: Medullary thyroid cancer (MTC) is characterized by early regional
      lymph node metastasis, the presence of which represents a critical obstacle to
      cure. At present no molecular markers have been successfully integrated into the
      clinical care of sporadic MTC. The present study was designed to evaluate
      TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the
      optimal extent of surgery performed with curative intent. METHODS: Thirty-eight
      patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied
      on embedded paraffin material and on cytological smears. RESULTS: TP53INP1 was
      expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was
      possible to identify two groups of MTC according to the proportion of TP53INP1
      expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of
      positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a
      lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with
      only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes
      versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus
      55.5%; P < 0.001). Patients with distant metastases were only observed in group
      2. Cytological samples exhibit similar results to their embedded counterparts.
      CONCLUSIONS: TP53INP1 immunoexpression appears to be a clinical predictor of
      lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the
      extent of lymph node dissection in the clinically node-negative neck. These
      findings require prospective validation.

PMID- 20145931
TI  - Aortic angiosarcoma: a rare cause for leaking thoracic aneurysm.
AB  - Primary malignant tumours of the aorta are rare. They present with aneurysm
      formation, arterial occlusion, and embolic phenomenon. We report the case of a 56
      year-old man whose initial presentation and investigations lead to emergency
      endovascular stenting of a descending thoracic aneurysm with a contained leak.
      Initial response was favourable, yet the patient presented again with worsening
      symptoms. The circum-aortic haematoma expanded by 50% on subsequent imaging, but
      no endoleak was identified. When altered bone marrow signal was identified on
      magnetic resonance imaging, the possibility of malignancy was considered. A
      metastatic skin lesion was then biopsied, which demonstrated morphological and
      immunohistochemical features consistent with metastases from a pleomorphic
      sarcoma of the aorta.

PMID- 20145932
TI  - Screening of bacterial isolates from polluted soils exhibiting catalase and
      peroxidase activity and diversity of their responses to oxidative stress.
AB  - For the survival of individual isolates of gram-negative bacteria Pseudomonas
      putida, Achromobacter xylosoxidans, and the gram-positive bacterium Bacillus
      megaterium, in an environment polluted with crude oil products, the production of
      catalases exhibiting both catalase and dianisidine-peroxidase activity is
      important. Electrophoretic resolution of cell-free extracts of aerobically grown
      strains in Luria-Bertani medium during exponential phase revealed distinctive
      expression of catalatic and peroxidatic activities detected with 3,3'
      diaminobenzidine tetrahydrochloride. A considerable diversity in microbial
      catalase and peroxidase responses to 20 or 40 mM H(2)O(2) stress, resulted from
      hydroperoxidase's variant of original isolates, indicating an environmental
      selective pressure. However, catalase was important for the adaptation of
      cultures to high concentration of 60 mM H(2)O(2). Appreciable differences in the
      sensitivity to toxic effect of H(2)O(2) (20 or 40 mM) treatment between
      individual isolates and their adapted variants during growth were observed until
      the middle of exponential phase, but they were insignificant at the entry to
      stationary phase. Isolates also exhibited a considerable diversity in catalases
      responses to phenolic contaminants 1 and 2 mM o- or p-phenylenediamine. Catalase
      activity of bacterium P. putida was visibly stimulated only by p-phenylenediamine
      and not by its positional isomer o-PDA. This study contributes to a better
      understanding of the role catalases play in bacterial responses to a polluted
      environment.

PMID- 20145933
TI  - Somatic embryogenesis and vegetative cutting capacity are under distinct genetic
      control in Coffea canephora Pierre.
AB  - The purpose of the study was to evaluate the possible genetic effect on
      vegetative propagation of Coffea canephora. Diversity for somatic embryogenesis
      (SE) ability was observed not only among two groups of C. canephora Pierre
      (Congolese and Guinean), but also within these different genetic groups. The
      results therefore showed that, under given experimental conditions, SE ability is
      depending on genotype. Furthermore the detection of quantitative trait loci
      (QTLs) controlling the SE and cutting abilities of C. canephora was performed on
      a large number of clones including accessions from a core collection, three
      parental clones and their segregating progenies. On the one hand we detected
      eight QTLs determining SE. Six positive QTLs for SE ability, whatever the
      criteria used to quantify this ability, were localized on one single chromosome
      region of the consensus genetic map. Two negative QTLs for SE ability (frequency
      of micro calli without somatic embryo) were detected on another linkage group.
      Deep analysis of the six QTLs detected for SE ability came to the conclusion that
      they can be assimilated to one single QTL explaining 8.6-12.2% of the observed
      variation. On the other hand, two QTLs for average length of roots and length of
      the longest sprouts of cuttings were detected in two linkage groups. These QTLs
      detected for cutting ability are explaining 12-27% of the observed variation.
      These observations led to conclude that SE and cutting abilities of C. canephora
      Pierre appeared to be genetic dependent but through independent mechanisms.

PMID- 20145934
TI  - Transcriptome analysis of secondary-wall-enriched seed coat tissues of canola
      (Brassica napus L.).
AB  - The seed coat of Brassica napus (canola, oilseed rape) is derived from ovule
      integuments and contains a layer of palisade cells, which have thick secondary
      walls. Because cellulosic walls and other indigestible components of the seed
      coat contribute negatively to the value of oilseeds, efforts are underway to
      alter seed development. To facilitate these efforts, and to better understand the
      biology of seed coats, we used a 90,000 element microarray to identify genes
      whose transcripts were expressed in developing seed coats of B. napus. After
      dissecting seed coats into three layers, and comparing transcript expression in
      the middle fraction (which contained the palisade-enriched tissue and bulk of
      inner integument) to transcript expression in developing hypocotyls, we
      identified 674 genes whose transcripts were more abundant in the middle fraction
      of the seed coat. Among these were well-characterized markers of seed coat
      identity and many genes associated with metabolism of cell wall polysaccharides,
      flavonoids and various cell wall proteins and transcription factors. Conversely,
      we identified 1,203 genes whose transcripts were more abundant in the hypocotyl
      tissue as compared to seed coat, including xylem-specific markers, such as XCP1
      and XCP2. We validated 21 of the differentially expressed transcripts using
      quantitative RT-PCR. The results define a set of transcripts that are highly
      enriched in the developing seed coat of B. napus.

PMID- 20145935
TI  - [Rational antibiotic therapy in ophthalmology].
AB  - Bacterial infections can affect all structures of the eye. In most cases,
      infections of the ocular surface are treatable with topical antibiotics, whereas
      intraocular infections need a combined treatment with intraocular and systemic
      antibiotics. Localisation, severity, expected microorganisms, and possible
      consequences of the infection lead to the appropriate therapy. Unwarranted use of
      antibiotic substances for prophylaxis or treatment of nonbacterial infection
      should be avoided, especially because of possible selection of multiresistant
      microorganisms.

PMID- 20145937
TI  - Elective laparoscopic recto-sigmoid resection for diverticular disease is
      suitable as a training operation.
AB  - PURPOSE: Some authors state that elective laparoscopic recto-sigmoid resection is
      more difficult for diverticular disease as compared with malignancy. For this
      reason, starting laparoscopic surgeons might avoid diverticulitis, making the
      implementation phase unnecessary long. The aim of this study was to determine
      whether laparoscopic resection for diverticular disease should be included during
      the implementation phase. METHODS: All consecutive patients who underwent an
      elective laparoscopic recto-sigmoid resection in our hospital for diverticulitis
      or cancer from 2003 to 2007 were analysed. RESULTS: A total of 256 consecutive
      patients were included in this prospective cohort study. One hundred and fifty
      one patients were operated on for diverticulitis and 105 for cancer. There was no
      significant difference in operation time (168 vs. 172 min), blood loss (189 vs.
      208 ml), conversion rates (9.9% vs. 11.4%), hospital stay (8 vs. 8 days), total
      number of peroperative (2.3% vs. 1.6%) or postoperative complications (21.9% vs.
      26.9%). The occurrence of anastomotic leakages was associated with higher
      American Society of Anesthesiologists (ASA) classification, which differed
      between the groups (86.8% vs. 64.8% ASA I-II, p < 0.001). CONCLUSION: Since there
      are no differences in operation time, blood loss, conversion rate and total
      complications, there is no need to avoid laparoscopic recto-sigmoid resection for
      diverticular disease early in the learning curve.

PMID- 20145936
TI  - Intraoperative neurophysiology of the motor system in children: a tailored
      approach.
AB  - INTRODUCTION: Intraoperative neurophysiology has moved giant steps forward over
      the past 15 years thanks to the advent of techniques aimed to reliably assess the
      functional integrity of motor areas and pathways. INTRAOPERATIVE
      NEUROPHYSIOLOGICAL TECHNIQUES: Motor evoked potentials recorded from the muscles
      and/or the spinal cord (D-wave) after transcranial electrical stimulation allow
      to preserve the integrity of descending pathways, especially the corticospinal
      tract (CT), during brain and spinal cord surgery. Mapping techniques allow to
      identify the motor cortex through direct cortical stimulation and to localize the
      CT at subcortical levels during brain and brainstem surgery. These techniques are
      extensively used in adult neurosurgery and, in their principles, can be applied
      to children. However, especially in younger children, the motor system is still
      under development, making both mapping and monitoring techniques more
      challenging. In this paper, we review intraoperative neurophysiological
      techniques commonly used in adult neurosurgery and discuss their application to
      pediatric neurosurgery, in the light of preliminary experience from our and other
      centers. The principles of development and maturation of the motor system, and
      especially of the CT, are reviewed focusing on clinical studies with transcranial
      magnetical stimulation.

PMID- 20145938
TI  - Sonographic assessment of lower uterine segment at term in women with previous
      cesarean delivery.
AB  - OBJECTIVE: To correlate lower uterine segment (LUS) thickness measured by
      abdominal sonography at term pregnancy with that measured manually using caliper
      at cesarean delivery and to find out minimum LUS thickness indicative of its
      integrity in women with previous cesarean. METHODS: In 106 women with previous
      cesarean delivery and 68 with unscarred uterus, abdominal sonographic assessment
      of LUS was carried out within a week of delivery. Sonographic measurements were
      correlated with manual measurement of lower flap of LUS using Vernier calipers in
      96 of these women (64 with previous cesarean and 32 of unscarred uterus) who had
      elective cesarean delivery. RESULTS: Sonographically determined LUS was thinner
      among women with previous cesarean delivery than in those without (4.58 SD 1.05
      vs. 4.8 SD 0.8; t = 1.986; p = 0.04). Women with vaginal birth after cesarean had
      thicker LUS than women with repeat cesarean delivery (4.4 SD 0.97 vs. 4.48 SD
      1.0). The findings were not influenced by engaged fetal head status or amount of
      bladder fullness. Directly measured LUS thickness using Vernier calipers before
      delivery of the baby confirmed ultrasound measurements, but showed smaller
      differences between them. There were eight cases with defective uterine scar at
      cesarean. LUS thickness at term of 3 mm provided 87.5% sensitivity and
      specificity, and was found to have negative predictive value of 98%. But in two
      of seven cases the actual LUS was not measurable despite sonographic measurement
      of 3 mm, and there were two records of scar dehiscence in those with 3 and 4 mm
      of LUS thickness. CONCLUSION: LUS thickness of 3 mm measured by abdominal
      ultrasonography prior to delivery at term in women with previous cesarean is
      suggestive of stronger LUS but is not a reliable safeguard for trial of labor.

PMID- 20145939
TI  - Ultrasonographic assessment of cervix size and its correlation with female
      characteristics, pregnancy, BMI, and other anthropometric features.
AB  - PURPOSE: Cervical length during the first trimester of pregnancy has not been
      completely investigated yet. The objective of our study is to compare cervical
      size in the first ten gestational weeks with that of non-pregnant women, and to
      determine its correlation with maternal factors, including age, anthropometric
      features, and reproductive history. METHODS: We collected retrospective data
      about women who applied to the Obstetrics and Gynecology Outpatients Facility of
      Udine between February and June 2009, selecting both pregnant and non-pregnant
      women possessing a transvaginal ultrasonographic measurement of their cervix, and
      focusing on their age, parity, BMI, cervical, and uterine size. Data were
      analyzed by R (version.2.8.0), considering significant P < 0.05. RESULTS: 135
      women were recruited. By multivariate linear regression, both cervical length and
      width result independently influenced by pregnancy status, and among non-pregnant
      nullipara, cervical length results to be significantly lower in women younger
      than 20 (P < 0.05). CONCLUSIONS: During the first ten gestational weeks, cervix
      results to be longer and wider than in non-pregnant women, suggesting the
      possible existence of early gestational, morphological, uterine, and cervical
      modifications. Women under the age of 20 have a significantly shorter cervix,
      suggesting an incomplete cervix maturity in this group of women, which may
      justify the higher prevalence of pre-term births in teenage pregnancies.

PMID- 20145940
TI  - Lethal thyroid storm after uncontrolled intake of liothyronine in order to lose
      weight.
AB  - Thyroid hormones are sometimes used for purposes for which they are not approved.
      Reasons for off-label use can be overweight, prevailing depressive mood, or
      various somatic symptoms. Information about the intake of thyroid hormones in
      order to lose weight can be easily obtained from inappropriate/nonmedical
      websites. The objective of this case report is to describe the first case of a
      lethal abuse of liothyronine. The case was a 29-year-old male (BMI 32) without
      relevant illnesses. An autopsy was performed and followed by histological,
      toxicological, and clinical chemistry examinations. The autopsy revealed no
      relevant pathology. Histology showed multiple areas of focal cell necrosis in the
      myocardium and signs of acute heart failure including severe edema of the lungs;
      the follicles of the thyroid gland were markedly plump. Postmortem laboratory
      results indicated lethal liothyronine intoxication. Despite prevailing opinion,
      uncontrolled intake of liothyronine can cause lethal thyroid storm in a euthyroid
      patient without manifested cardiac illnesses.

PMID- 20145942
TI  - Is post-mortem CT of the dentition adequate for correct forensic identification?
      Comparison of dental computed tomography and visual dental record.

PMID- 20145943
TI  - Magnitude-dependent variation in peak height balance at heterozygous STR loci.
AB  - When the smaller of two peaks at an STR locus is less than 70% the magnitude of
      the larger peak at that locus, the disparity is typically taken to be an
      indication that there is more than one contributor of template DNA to the sample
      being tested. An analysis of 1,763 heterozygous allele pairs suggests that a peak
      height imbalance threshold that varies with the magnitude of the peaks being
      evaluated at a locus is superior to a fixed threshold. Identifying samples that
      are likely to be mixtures and those that are likely to have arisen from a single
      source is accomplished more reliably when a statistically based, magnitude
      dependent peak height imbalance threshold is used. The amelogenin locus was found
      to behave in a similar fashion and was also found to have no systematic bias that
      favored the amplification of Y or X alleles.

PMID- 20145944
TI  - MicroRNA markers for forensic body fluid identification obtained from microarray
      screening and quantitative RT-PCR confirmation.
AB  - MicroRNAs (miRNAs) are non-protein coding molecules with important regulatory
      functions; many have tissue-specific expression patterns. Their very small size
      in principle makes them less prone to degradation processes, unlike messenger
      RNAs (mRNAs), which were previously proposed as molecular tools for forensic body
      fluid identification. To identify suitable miRNA markers for forensic body fluid
      identification, we first screened total RNA samples derived from saliva, semen,
      vaginal secretion, and venous and menstrual blood for the expression of 718 human
      miRNAs using a microarray platform. All body fluids could be easily distinguished
      from each other on the basis of complete array-based miRNA expression profiles.
      Results from quantitative reverse transcription PCR (RT-PCR; TaqMan) assays for
      microarray candidate markers confirmed strong over-expression in the targeting
      body fluid of several miRNAs for venous blood and several others for semen.
      However, no candidate markers from array experiments for other body fluids such
      as saliva, vaginal secretion, or menstrual blood could be confirmed by RT-PCR.
      Time-wise degradation of venous blood and semen stains for at least 1 year under
      lab conditions did not significantly affect the detection sensitivity of the
      identified miRNA markers. The detection limit of the TaqMan assays tested for
      selected venous blood and semen miRNA markers required only subpicogram amounts
      of total RNA per single RT-PCR test, which is considerably less than usually
      needed for reliable mRNA RT-PCR detection. We therefore propose the application
      of several stable miRNA markers for the forensic identification of blood stains
      and several others for semen stain identification, using commercially available
      TaqMan assays. Additional work remains necessary in search for suitable miRNA
      markers for other forensically relevant body fluids.

PMID- 20145946
TI  - Evaluation of three portable blood lactate analysers: Lactate Pro, Lactate Scout
      and Lactate Plus.
AB  - Three portable blood lactate analysers, Lactate Pro (LP), Lactate Scout (LS) and
      Lactate Plus (L(+)), were evaluated. Analyser reliability and accuracy was
      assessed. For reliability, intra- and inter-analyser comparisons demonstrated
      that the LP (intra-TE = 0.5 mM, inter-TE = 0.4 mM) and L(+) (intra-TE = 0.4,
      inter-TE = 0.4 mM) displayed greater overall reliability than the LS (intra-TE =
      1.0, inter-TE = 0.8 mM). At BLa < 4.0 mM, the LP (intra-TE = 0.1 mM) demonstrated
      greater reliability than the LS (intra-TE = 0.5 mM) and L(+) (intra-TE = 0.4 mM).
      At BLa > 8.0 mM, the LP (intra-TE = 0.5 mM, inter-TE = 0.4 mM) and L(+) (intra-
      and inter-TE = 0.4 mM) displayed greater reliability than the LS (intra-TE = 1.1
      mM, inter-TE = 0.9 mM). For accuracy, the L(+) (SEE = 0.6 mM) compared more
      favourably to the LP than the LS (SEE = 1.1 mM). At BLa approximately 1.0-18.0
      mM, the LS produced values that were up to 0.9 mM higher than the LP; the L(+)
      produced BLa that were within +/-0.1 mM. All portable analysers tended to under
      read the ABL 700 analyser. The suitability of the LP and L(+) as accurate
      analysers is supported by strong correlations (r = 0.91 and r = 0.94) and limits
      of agreement <or=2.1 mM. This study showed that the LP and L(+), compared well to
      each other, displayed good reliability and accuracy when compared to a laboratory
      based analyser. Although the LS also displayed relatively good reliability, it
      was not as reliable or accurate as the LP or L(+).

PMID- 20145945
TI  - Increased protein synthesis by cells exposed to a 1,800-MHz radio-frequency
      mobile phone electromagnetic field, detected by proteome profiling.
AB  - PURPOSE: To investigate whether or not low intensity radio frequency
      electromagnetic field exposure (RF-EME) associated with mobile phone use can
      affect human cells, we used a sensitive proteome analysis method to study changes
      in protein synthesis in cultured human cells. METHODS: Four different cell kinds
      were exposed to 2 W/kg specific absorption rate in medium containing 35S
      methionine/cysteine, and autoradiography of 2D gel spots was used to measure the
      increased synthesis of individual proteins. RESULTS: While short-term RF-EME did
      not significantly alter the proteome, an 8-h exposure caused a significant
      increase in protein synthesis in Jurkat T-cells and human fibroblasts, and to a
      lesser extent in activated primary human mononuclear cells. Quiescent
      (metabolically inactive) mononuclear cells, did not detectably respond to RF-EME.
      Since RF exposure induced a temperature increase of less than 0.15 degrees C, we
      suggest that the observed cellular response is a so called "athermal" effect of
      RF-EME. CONCLUSION: Our finding of an association between metabolic activity and
      the observed cellular reaction to low intensity RF-EME may reconcile conflicting
      results of previous studies. We further postulate that the observed increased
      protein synthesis reflects an increased rate of protein turnover stemming from
      protein folding problems caused by the interference of radio-frequency
      electromagnetic fields with hydrogen bonds. Our observations do not directly
      imply a health risk. However, vis-a-vis a synopsis of reports on cells stress and
      DNA breaks, after short and longer exposure, on active and inactive cells, our
      findings may contribute to the re-evaluation of previous reports.

PMID- 20145947
TI  - Predicting VO(2max) with an objectively measured physical activity in Japanese
      men.
AB  - The present study investigated the use of the accelerometer-determined physical
      activity (PA) variables as the objective PA variables for estimating VO(2max) in
      Japanese adult men. One hundred and twenty-seven Japanese adult men aged from 20
      to 69 years were recruited as subjects of the present study. Maximal oxygen
      uptake VO(2max) was measured with a maximal incremental test on a bicycle
      ergometer. Daily step counts (SC) and the amount spent in moderate to vigorous PA
      (MVPA) and vigorous PA (VPA) were measured using accelerometer-based activity
      monitors worn at the waist for seven consecutive days. The non-exercise models
      were derived using hierarchical linear regression analysis, and cross-validated
      using two separate cross-validation procedures. SC, MVPA, and VPA were
      significantly related to VO(2max) (partial correlation coefficient r = 0.58, r =
      0.42, and r = 0.51, respectively) after adjusting for age. Two models were
      developed by multiple regression to estimate VO(2max) using data of age, SC, VPA,
      and either BMI (the coefficient of determination (R(2)) = 0.71, standard error of
      estimate (SEE) = 4.2 ml kg(-1) min(-1)), or waist circumference (R(2) = 0.74, SEE
      = 3.9 ml kg(-1) min(-1)). All regression models demonstrated a high level of
      cross-validity supported by the minor shrinkage of R(2) and increment of SEE in
      the PRESS procedure, and by small constant errors for subgroups of age, SC, and
      VO(2max). This study demonstrated that combining SC with VPA, but not with MVPA,
      was useful in predicting VO(2max) variance and improved the ability of the
      regression models to accurately predict VO(2max).

PMID- 20145948
TI  - Yearlong physical activity and regional stiffness of arteries in older adults:
      the Nakanojo Study.
AB  - Our objectives were to test the hypothesis that the habitual physical activity of
      elderly individuals is associated with less arterial stiffening, to explore
      characteristics of any dose/response relationship, and to determine those
      segments of the arterial tree where associations are most apparent. Participants
      (89 men and 109 women, aged 65-84) wore a pedometer/accelerometer continuously
      for 1 year. The daily step count and the duration of moderate-intensity activity
      (>3 metabolic equivalents, METs) were recorded. At year's end, an automatic
      waveform analyzer determined the pulse wave velocity between five recording
      sites: the aortic root, and the carotid, brachial, femoral and tibial arteries.
      After appropriate adjustments for sex, age, and mean arterial pressure, overall
      (delta brachio-tibial "velocity") and central arterial stiffness (cardio-femoral
      velocity) showed small but statistically significant negative correlations with
      daily step count and the duration of activity >3 METs. Cardio-carotid velocity
      was also associated with step count. In contrast, cardio-brachial and femoro
      tibial velocities were not significantly related to either estimate of habitual
      activity. Cardio-femoral and delta brachio-tibial velocities were significantly
      lower in physically active individuals, apparently reaching a minimum in subjects
      who exceeded counts of about 6,600 steps/day and/or exercised for more than 16
      min/day at an intensity >3 METs. The data support our hypothesis, showing weak
      but statistically significant associations between habitual physical activity and
      pulse wave assessments of arterial stiffness in elderly adults. Further studies
      are recommended to test the causality of these associations and to explore why
      relationships seem more marked for central than for peripheral arterial segments.

PMID- 20145949
TI  - A functional EDS1 ortholog is differentially regulated in powdery mildew
      resistant and susceptible grapevines and complements an Arabidopsis eds1 mutant.
AB  - Vitis vinifera (grapevine) is the most economically important deciduous fruit
      crop, but cultivated grapevine varieties lack adequate innate immunity to a range
      of devastating diseases. To identify genetic resources for grapevine innate
      immunity and understand pathogen defense pathways in a woody perennial plant, we
      focus in this study on orthologs of the central Arabidopsis thaliana defense
      regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). The family of EDS1-like genes
      is expanded in grapevine, and members of this family were previously found to be
      constitutively upregulated in the resistant variety 'Norton' of the North
      American grapevine species Vitis aestivalis, while they were induced by Erysiphe
      necator, the causal agent of grapevine powdery mildew (PM), in the susceptible V.
      vinifera variety 'Cabernet Sauvignon'. Here, we determine the responsiveness of
      individual EDS1-like genes in grapevine to PM and salicylic acid, and find that
      EDS1-like paralogs are differentially regulated in 'Cabernet Sauvignon', while
      two are constitutively upregulated in 'Norton'. Sequencing of VvEDS1 and VaEDS1
      cDNA and genomic clones revealed high conservation in the protein-encoding
      sequence and some divergence of the promoter sequence in the two grapevine
      varieties. Complementation of the Arabidopsis eds1-1 mutant showed that the EDS1
      like gene with highest predicted amino acid sequence similarity to AtEDS1 from
      either grapevine varieties is a functional ortholog of AtEDS1. Together, our
      analyses show that differential susceptibility to PM is correlated with
      differences in EDS1 expression, not differences in EDS1 function, between
      resistant 'Norton' and susceptible 'Cabernet Sauvignon'.

PMID- 20145950
TI  - Nitric oxide mediates humic acids-induced root development and plasma membrane H+
      ATPase activation.
AB  - It is widely reported that some humic substances behave as exogenous auxins
      influencing root growth by mechanisms that are not yet completely understood.
      This study explores the hypothesis that the humic acids' effects on root
      development involve a nitric oxide signaling. Maize seedlings were treated with
      HA 20 mg C L(-1), IAA 0.1 nM, and NO donors (SNP or GSNO), in combination with
      either the auxin-signaling inhibitor PCIB, the auxin efflux inhibitor TIBA, or
      the NO scavenger PTIO. H(+)-transport-competent plasma membrane vesicles were
      isolated from roots to investigate a possible link between NO-induced H(+)-pump
      and HA bioactivity. Plants treated with either HA or SNP stimulated similarly the
      lateral roots emergence even in the presence of the auxin inhibitors, whereas NO
      scavenger diminished this effect. These treatments induced H(+)-ATPase
      stimulation by threefold, which was abolished by PTIO and decreased by auxin
      inhibitors. HA-induced NO synthesis was also detected in the sites of lateral
      roots emergence. These data depict a new scenario where the root development
      stimulation and the H(+)-ATPase activation elicited by either HA or exogenous IAA
      depend essentially on mechanisms that use NO as a messenger induced site
      specifically in the early stages of lateral root development.

PMID- 20145951
TI  - Induction of MKP-1 prevents the cytotoxic effects of PI3K inhibition in hilar
      cholangiocarcinoma cells.
AB  - PURPOSE: Hilar cholangiocarcinoma (Klatskin tumor) is one of the most difficult
      cancers to treat. We demonstrate activation of phosphoinositide-3-kinase
      (PI3K)/Akt signaling, which is a critical pathway for cell survival, in hilar
      cholangiocarcinoma cells. However, inhibition of PI3K has little effect on hilar
      cholangiocarcinoma cell survival. In this study, we investigated the mechanism by
      which hilar cholangiocarcinoma cells resist PI3K inhibitors. METHODS: Human hilar
      cholangiocarcinoma cells KKU-100 were treated with PI3K inhibitors, and cell
      viability and apoptosis assays were performed. The expression of a MAPK
      phosphatase (MKP-1) that contributes to cancer cell survival in response to
      multiple stress stimuli was assayed by quantitative real-time RT-PCR and western
      blotting. In addition, the effects of the MKP-1 inhibitor were studied in KKU-100
      cells treated with PI3K inhibitors. RESULTS: Incubation of KKU-100 cells with
      PI3K inhibitors resulted in increased expression of MKP-1. Furthermore, we found
      that inhibition of MKP-1 using siRNA silencing sensitized KKU-100 cells to PI3K
      inhibitor-induced apoptosis via increased phosphorylation of p38 MAPK.
      CONCLUSIONS: These results indicate that concurrent inhibition of PI3K and MKP-1
      induces apoptosis in KKU-100 cells. Simultaneous targeting of the PI3K pathway
      and MKP-1 may be a useful approach to improve therapies directed against hilar
      cholangiocarcinoma.

PMID- 20145953
TI  - Relationships among bather density, levels of human waterborne pathogens, and
      fecal coliform counts in marine recreational beach water.
AB  - During summer months, samples of marine beach water were tested weekly for human
      waterborne pathogens in association with high and low bather numbers during
      weekends and weekdays, respectively. The numbers of bathers on weekends were
      significantly higher than on weekdays (P < 0.001), and this was associated with a
      significant (P < 0.04) increase in water turbidity. The proportion of water
      samples containing Cryptosporidium parvum, Giardia duodenalis, and Enterocytozoon
      bieneusi was significantly higher (P < 0.03) on weekends than on weekdays, and
      significantly (P < 0.01) correlated with enterococci counts. The concentration of
      all three waterborne pathogens was significantly correlated with bather density
      (P < 0.01). The study demonstrated that: (a) human pathogens were present in
      beach water on days deemed acceptable for bathing according to fecal bacterial
      standards; (b) enterococci count was a good indicator for the presence of
      Cryptosporidium, Giardia, and microsporidian spores in recreational marine beach
      water; (c) water should be tested for enterococci during times when bather
      numbers are high; (d) re-suspension of bottom sediments by bathers caused
      elevated levels of enterococci and waterborne parasites, thus bathers themselves
      can create a non-point source for water contamination; and (e) exposure to
      recreational bathing waters can play a role in epidemiology of microsporidiosis.
      In order to protect public health, it is recommended to: (a) prevent diapered
      children from entering beach water; (b) introduce bather number limits to
      recreational areas; (c) advise people with gastroenteritis to avoid bathing; and
      (d) use showers prior to and after bathing.

PMID- 20145952
TI  - Association of the GNB3 825T-allele with better survival in patients with
      glioblastoma multiforme.
AB  - PURPOSE: Genotypes of the C825T polymorphism of the GNB3 gene encoding the G
      protein beta3 subunit were recently associated with the prognosis of different
      malignomas. We investigated potential associations of GNB3 genotypes with
      survival of patients with glioblastoma multiforme (GBM). METHODS: One hundred and
      sixty-one patients suffering from GBM were retrospectively investigated.
      Inclusion criteria were availability of DNA and a follow-up of at least 24
      months. The results were evaluated with respect to the basic clinical data, type
      of surgical intervention, MGMT promoter methylation, adjuvant therapy, and
      survival. RESULTS: After 2 years of first diagnosis, 128 (79.5%) of the 161
      patients had died, 33 (20.5%) were alive. Kaplan-Meier curves revealed a
      significant higher rate of survival for homo- and heterozygous T-allele carriers
      (P = 0.019) with 38.5 and 25.3%, respectively, but only 11.6% for homozygous C
      allele carriers. Multivariable Cox regression identified the heterozygous (hazard
      ratio 3.3, 95% CI 1.3-8.0, P = 0.010), as well as homozygous GNB3 825 C-allele
      (hazard ratio 3.7, 95% CI 1.5-9.1, P = 0.004) as an independent negative
      prognostic factor for 2-year survival according to the GNB3 825 TT genotype
      reference group. CONCLUSIONS: Our data suggest an association of the GNB3 825TT
      genotype and better survival in patients with GBM.

PMID- 20145954
TI  - Forensically important flesh fly species in Thailand: morphology and
      developmental rate.
AB  - Forensically important flesh fly species in Thailand have been investigated for
      their larval morphology and developmental rate to increase the forensic
      entomology database in Thailand and nearby countries. Sarcophaga (Liosarcophaga)
      dux Thomson, Sarcophaga (Liopygia) ruficornis (Fabricius), and Sarcophaga
      (Boettcherisca) peregrina (Robineau-Desvoidy) are the species of greatest
      forensic importance. The third instars of these species are similar in
      morphological appearance, making it difficult or impossible to differentiate
      between them based on external morphological characteristics. This study compares
      these important characteristics and reveals that the most distinctive is the
      posterior spiracle, followed by the number of papillae on the anterior spiracle.
      For confirmation of these species, the unique characteristics of adult males are
      also shown for accurate identification. Both the third instar and adult male
      characteristics are keys to identifying these species. In addition, the
      developmental rate of S. dux was examined in northern Thailand during 2002-2003
      under natural ambient temperature (approximately 24-28 degrees C) and a natural
      light/dark photoperiod (approximately 12:12 h), indicating relatively rapid
      larval development in summer (March-June), pre-pupae (stop moving) initiated at
      72 h. In the rainy season (July-October), pre-pupae initiated at 72 or 96 h,
      whereas pre-pupae initiated at 96 h in winter.

PMID- 20145955
TI  - Hemolytic uremic syndrome caused by Bordetella pertussis infection.
AB  - We report the case of a 4-week-old infant with severe Bordetella pertussis
      infection resulting in hemolytic anemia, thrombocytopenia, and acute renal
      failure leading to a diagnosis of hemolytic uremic syndrome (HUS) associated with
      pertussis. In addition to antibiotic and supportive therapy, he was treated with
      plasma transfusions based on the possibility of underlying complement defect, and
      he improved. The association of B. pertussis infection and HUS has previously
      been described in a patient with a mutation in the gene encoding complement
      factor H (CFH). However, whereas a genetic workup for complement regulator
      mutations was performed, no mutation was found in our patient. This case
      demonstrates the possible association between pertussis infection and HUS and
      highlights the need for increased vigilance for renal complications in this
      diagnosis. Despite negative results in this case, in-depth workup of the
      complement system may be important to guide treatment efforts and strategies.

PMID- 20145957
TI  - Dual growth rods for infantile scoliosis.

PMID- 20145956
TI  - A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from
      the MASCC skin toxicity study group.
AB  - BACKGROUND: Accurate grading of dermatologic adverse events (AE) due to epidermal
      growth factor receptor (EGFR) inhibitors (EGFRIs) is necessary for drug toxicity
      determinations, interagent comparisons, and supportive care trials. The most
      widely used severity grading scale, the National Cancer Institute's Common
      Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0), was not
      designed specifically for this class of agents and may result in underreporting
      and poor grading of distinctive adverse events. We believe a class-specific
      grading scale is needed to help standardize assessment and improve reporting of
      EGFRI-associated dermatologic AEs. METHODS: The Multinational Association of
      Supportive Care in Cancer (MASCC) Skin Toxicity Study Group conducted an
      international multidisciplinary meeting that included 20 clinicians and
      researchers from academic centers and government agencies. Experts from different
      disciplines presented current information specific to EGFRI-induced dermatologic
      toxicities: grading scale development, pharmacovigilance safety reporting, health
      related quality of life, patient reporting, and pharmacology. Group discussions,
      literature reviews, and professional expertise established the theoretical
      foundation for the proposed grading scale. RESULTS: A new grading system is
      proposed for the most common events associated with EGFRI-induced dermatologic
      AEs: papulopustular reaction or acneiform rash, nail changes, erythema, pruritus,
      xerosis, hair changes, telangiectasias, hyperpigmentation, mucositis, flushing,
      radiation dermatitis, hyposalivation, and taste changes. The proposed scale
      maintains consistency with the grading principles and language of the existing
      CTCAE version 4.0 and MedDRA terminology and includes relevant patient-reported
      health-related quality of life factors. CONCLUSIONS: A grading scale specific to
      EGFR inhibitor dermatologic AEs is presented for formal integration into future
      versions of CTCAE and for validation in clinical trial settings. The study group
      designed this scale to detect and report EGFRI-related toxicities with greater
      sensitivity, specificity, and range than the scales currently used. This scale
      should serve as a foundation for efforts to perform objective interdrug
      comparisons and assessments of supportive care treatment strategies more
      effectively than with current methods.

PMID- 20145958
TI  - Ankylosing spondylitis neural and sparing osteotomy.

PMID- 20145959
TI  - Gamma-glutamyl 16-diaminopropane derivative of vasoactive intestinal peptide: a
      potent anti-oxidative agent for human epidermoid cancer cells.
AB  - We previously demonstrated that the gamma-glutamyl 16 amine derivative of
      vasoactive intestinal peptide (VIP) acts as structural VIP agonist with affinity
      and potency higher than VIP. Herein, we have evaluated the effects of VIP and
      gamma-Gln16-diaminopropane derivative of VIP (VIP-DAP3) on the proliferation and
      protection from oxidative stress induced by hydrogen peroxide (H2O2) on
      epidermoid carcinoma cell lines. We have found that 10(-11) M VIP-DAP3 completely
      antagonized the inhibition induced by H2O2 on both cell proliferation and S-phase
      distribution while these effects were only partially antagonized by equimolar
      concentrations of VIP. Moreover, both oxidative stress and intracellular lipid
      oxidation induced by H2O2 were reduced by VIP and completely antagonized by VIP
      DAP3. Thereafter, we have found that H2O2 increased p38 kinase activity and both
      HSP70 and HSP27 expression. VIP and VIP-DAP3 again antagonized these effects
      partially or totally, respectively. H2O2 reduced the activity of extracellular
      signal-regulated kinases Erk-1/2 and Akt, signalling proteins involved in
      proliferation/survival pathways. Again VIP restored the activity of both kinases
      while VIP-DAP3 caused indeed an increase of their activity as compared to
      untreated cells. These data suggest that VIP-DAP3 has a stronger anti-oxidative
      activity as compared to VIP likely based on its super-agonistic binding on the
      putative receptor.

PMID- 20145960
TI  - Beneficial effects of vitamin E isomer supplementation on static and dynamic bone
      histomorphometry parameters in normal male rats.
AB  - Bone is a specialized connective tissue that functions as the load-bearing
      structure of the body. Free radicals may affect bone remodeling by regulating
      osteoclast activity in either the physiological or pathological condition.
      Vitamin E, a lipid-soluble antioxidant, has been demonstrated to offer protection
      against osteoporosis and to improve the bone material and structure of animal
      models. The aim of this study was to observe and compare the effects of alpha
      tocopherol (alpha-tocopherol), delta-tocotrienol (delta-tocotrienol), and gamma
      tocotrienol (gamma-tocotrienol) on the static and dynamic bone histomorphometric
      parameters in normal male rats. Thirty-two normal Sprague-Dawley male rats aged 3
      months and weighing 200-250 g were randomly divided into four groups. The control
      group was supplemented with oral gavages of olive oil (vehicle), whereas the
      alpha-tocopherol, delta-tocotrienol, and gamma-tocotrienol groups were given oral
      gavages of 60 mg/kg alpha-tocopherol, delta-tocotrienol, and gamma-tocotrienol,
      respectively. The rats were injected twice with calcein to fluorochrome-label the
      bones. After 4 months of treatment, the rats were killed, and the left femurs
      were dissected out and prepared for bone histomorphometry. Both the static and
      dynamic parameters of the vitamin E-treated groups were better than those of the
      normal control group. Among the vitamin E-treated groups, the tocotrienol groups
      showed better histomorphometry results compared to the alpha-tocopherol group,
      with the gamma-tocotrienol group demonstrating the best effects on both sets of
      parameters. We concluded that vitamin E can promote bone formation in normal
      rats, with gamma-tocotrienol being the most potent form of vitamin E.

PMID- 20145961
TI  - Inorganic polyphosphate differentiates human mesenchymal stem cells into
      osteoblastic cells.
AB  - The existence of inorganic polyphosphates [poly(P)] in human cells has been
      demonstrated. In osteoblasts, it is suggested that the concentration of cellular
      poly(P) is relatively high. In this study, we examined whether poly(P)
      accelerates the differentiation of human mesenchymal stem cells (hMSCs) from
      patients with osteoarthritis (OA) and rheumatoid arthritis (RA) into osteoblastic
      cells. Alkaline phosphatase (ALP) activity was induced by poly(P) in hMSCs from
      both OA and RA. In Alizarin Red S and osteocalcin EIA, there was a significant
      difference between the control and poly(P) group. In real-time PCR, there was a
      significant difference in ALP, collagen type 1A, osteocalcin, and bone
      sialoprotein between the control and poly(P) group. Our findings suggest that
      poly(P) have the potent role of differentiating hMSCs into osteoblastic cells at
      the early and later stages of osteoblastic differentiation.

PMID- 20145964
TI  - Poliomyelitis causing TMJ ankylosis?--report of two intriguing cases.
AB  - INTRODUCTION: Temporomandibular joint (TMJ) ankylosis is one of the common
      diseases which affect the TMJ especially in children. We are reporting two rare
      cases of TMJ ankylosis which occurred along with poliomyelitis and which are not
      reported in literature so far. DISCUSSION: In this article, we discussed about
      the most probable causes which resulted in TMJ ankylosis in these patients.

PMID- 20145963
TI  - Osteoradionecrosis of the jaws--a current overview--Part 2: dental management and
      therapeutic options for treatment.
AB  - PURPOSE: The aim of this paper is to explore the current theories about
      pretreatment assessment and dental management of patients receiving head and neck
      radiotherapy, and the therapeutic options to treat osteoradionecrosis of the
      jaws, based on the literature review. DISCUSSION: Osteoradionecrosis is one of
      the most serious oral complications of head and neck cancer treatment.
      Osteoradionecrosis is a severe delayed radiation-induced injury, characterized by
      bone tissue necrosis and failure to heal. Osteoradionecrosis either stabilizes or
      gradually worsens and is notoriously difficult to manage. Because most cases
      occur in patients who were dentulous in the mandible at tumor onset, proper
      dental management is the single most important factor in prevention. CONCLUSIONS:
      Complete dental clearance before treatment is no longer necessary. Controversy
      exists regarding the management of osteoradionecrosis of the maxillofacial
      skeleton because of the variability of this condition. The treatment of
      osteoradionecrosis has included local wound care, antibiotic therapy, surgical
      procedures, and the administration of hyperbaric oxygenation. Recently, new
      methods of treatment were introduced, according to the new theory about its
      pathophysiology.

PMID- 20145962
TI  - Molecular genetics of attention-deficit/hyperactivity disorder: an overview.
AB  - As heritability is high in attention-deficit/hyperactivity disorder (ADHD),
      genetic factors must play a significant role in the development and course of
      this disorder. In recent years a large number of studies on different candidate
      genes for ADHD have been published, most have focused on genes involved in the
      dopaminergic neurotransmission system, such as DRD4, DRD5, DAT1/SLC6A3, DBH, DDC.
      Genes associated with the noradrenergic (such as NET1/SLC6A2, ADRA2A, ADRA2C) and
      serotonergic systems (such as 5-HTT/SLC6A4, HTR1B, HTR2A, TPH2) have also
      received considerable interest. Additional candidate genes related to
      neurotransmission and neuronal plasticity that have been studied less intensively
      include SNAP25, CHRNA4, NMDA, BDNF, NGF, NTF3, NTF4/5, GDNF. This review article
      provides an overview of these candidate gene studies, and summarizes findings
      from recently published genome-wide association studies (GWAS). GWAS is a
      relatively new tool that enables the identification of new ADHD genes in a
      hypothesis-free manner. Although these latter studies could be improved and need
      to be replicated they are starting to implicate processes like neuronal migration
      and cell adhesion and cell division as potentially important in the aetiology of
      ADHD and have suggested several new directions for future ADHD genetics studies.

PMID- 20145965
TI  - Activation of human mononuclear cells by porcine biologic meshes in vitro.
AB  - INTRODUCTION: While porcine-based biologic meshes are increasingly used for
      hernia repair, little data exist on tissue responses to such products. Host
      foreign body reaction, local inflammation, and wound healing are principally
      controlled by monocytes/macrophages (M/MOs). Exaggerated activation of M/MOs may
      deleteriously influence mesh integration and remodeling. We hypothesized that
      common porcine meshes induce the differential activation of M/MOs in vitro.
      MATERIALS AND METHODS: Samples of four acellular porcine-derived meshes,
      CollaMend (CM; C.R. Bard/Davol), Permacol (PC; TSL/Covidien), Strattice (ST;
      LifeCell), and Surgisis (SS; Cook Biotech), were exposed to mononuclear cells
      derived from the peripheral blood of six healthy subjects. Following a 7-day
      incubation period, supernatants were assayed for interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth
      factor (VEGF) using a multiplex bead-based immunoassay system. The four groups
      were compared using analysis of variance (ANOVA) and Student's t-test. RESULTS:
      Each mesh type induced differential mononuclear cell activation in vitro. The
      mean IL-1beta expressions for CM (7,195 pg/ml) and PC (4,215 pg/ml) were
      significantly higher compared to ST and SS (123 and 998 pg/ml, respectively; P <
      0.05). Similar trends were also seen for IL-6 (range 445-70,729 pg/ml), IL-8
      (range 11,640-1,045,938 pg/ml), and VEGF (range 686-7,133 pg/ml). CONCLUSION: For
      the first time, we demonstrated that porcine meshes induce M/MO activation in
      vitro. CM and PC (chemically crosslinked dermis) induced significantly higher
      cytokine expression compared to ST (non-crosslinked dermis) and SS (small
      intestine submucosa). These differences are likely related to proprietary
      processing methods and/or the extent of collagen crosslinking. Further
      understanding of immunologic effects of porcine-derived biologic meshes will not
      only allow for a comparison between existing products, but it may also lead to
      mesh modifications and improvement of their clinical performance.

PMID- 20145966
TI  - Influence of nerve identification and the resection of nerves 'at risk' on
      postoperative pain in open inguinal hernia repair.
AB  - BACKGROUND: Surgical strategy regarding nerve identification and resection in
      relation to chronic postoperative pain remains controversial. A central question
      is whether nerves in the operation field, when identified, should be preserved or
      resected. In the present study, the hypotheses that the identification and
      consequent resection of nerves 'at risk' have no influence on postoperative pain
      has been tested. METHODS: A single-centre study was conducted in 525 patients
      undergoing Lichtenstein hernioplasty. One surgeon (364 operations, Group A)
      consequently resected nerves 'at risk' for being injured and nine surgeons (161
      operations, Group B) adhered to the general routine of nerve preservation. All
      cases were ambulatory surgery on anaesthetised patients and the groups were
      similar with regard to age, body mass index (BMI) and preoperative pain. Self
      reported pain at 3 months was recorded on a 10-box visual analogue scale (VAS).
      The identification and resection of nerves were continuously registered.
      Statistical calculations were performed with Fisher's exact test and ordinal
      logistic regression. RESULTS: There was no significant difference in the number
      of identified nerves in the two groups of patients (iliohypogastricus, P = 0.555;
      ilioinguinalis, P = 0.831; genital branch, P = 0.214). However, the number of
      resected nerves was significantly higher in Group A for the iliohypogastric
      nerve, P < 0.001, but not for ilioinguinalis, P = 0.064, and genital branch, P =
      0.362. Non-identification of the ilioinguinal nerve correlated to the highest
      level of self-reported postoperative pain at 3 months. Patients in Group A, who
      had nerves 'at risk' resected from the operation field, reported significantly
      less postoperative pain at 3 months, P = 0.007. CONCLUSION: This register study
      confirms the importance of nerve identification. Nerve resection strategy with
      the consequent removal of nerves 'at risk' gives a significantly better outcome
      in Lichtenstein hernioplasty.

PMID- 20145967
TI  - Diagnosis, treatment and follow-up of the carpal tunnel syndrome: a review.
AB  - The carpal tunnel syndrome is a compressive neuropathy with high incidence rates,
      and its correct diagnosis, treatment and follow-up may lead to significant
      benefits in healthcare, social and economic terms. In this review, based on
      systematic review databases and guidelines, we summarise the appropriate
      indications for the diagnosis, treatment and follow-up, accompanied, whenever
      possible, by the levels of evidence and strength of recommendations.

PMID- 20145968
TI  - Carbonized blood deposited on fibres during 810, 940 and 1,470 nm endovenous
      laser ablation: thickness and absorption by optical coherence tomography.
AB  - Endovenous laser ablation (EVLA) is commonly used to treat saphenous
      varicosities. Very high temperatures at the laser fibre tip have been reported
      during EVLA. We hypothesized that the laser irradiation deposits a layer of
      strongly absorbing carbonized blood of very high temperature on the fibre tip. We
      sought to prove the existence of these layers and study their properties by
      optical transmission, optical coherence tomography (OCT) and microscopy. We
      analysed 23 EVLA fibres, 8 used at 810 nm, 7 at 940 nm and 8 at 1,470 nm. We
      measured the transmission of these fibres in two wavelength bands (450-950 nm;
      950-1,650 nm). We used 1,310 nm OCT to assess the thickness of the layers and the
      attenuation as a function of depth to determine the absorption coefficient.
      Microscopy was used to view the tip surface. All fibres showed a slightly
      increasing transmission with wavelength in the 450-950 nm band, and a virtually
      wavelength-independent transmission in the 950-1,650 nm band. OCT scans showed a
      thin layer deposited on all 13 fibres investigated, 6 used at 810 nm, 4 at 940 nm
      and 3 at 1,470 nm, some with inhomogeneities over the tip area. The average
      absorption coefficient of the 13 layers was 72 +/- 16 mm(-1). The average layer
      thickness estimated from the transmission and absorption measurements was 8.0 +/-
      2.7 microm. From the OCT data, the average maximal thickness was 26 +/- 6 microm.
      Microscopy of three fibre tips, one for each EVLA wavelength, showed rough,
      cracked and sometimes seriously damaged tip surfaces. There was no clear
      correlation between the properties of the layers and the EVLA parameters such as
      wavelength, except for a positive correlation between layer thickness and total
      delivered energy. In conclusion, we found strong evidence that all EVLA
      procedures in blood filled veins deposit a heavily absorbing hot layer of
      carbonized blood on the fibre tip, with concomitant tip damage. This major EVLA
      mechanism is unlikely to have much wavelength dependence at similar delivered
      energies per centimetre of vein. Optical-thermal interaction between the vein
      wall and the transmitted laser light depends on wavelength.

PMID- 20145970
TI  - Adverse selection in the health insurance market: some empirical evidence.
AB  - This paper tests for the existence of adverse selection in the Brazilian
      individual health insurance market in 2003. The testing approach adapts that
      conceived by Chiappori and Salanie (Eur Econ Rev 41, 943-950, 1997; J Polit Econ
      108, 56-78, 2000). After controlling for sex, age, income, number of dependents,
      occupational groups and schooling levels, the evidence favors adverse selection
      as indicated by a positive correlation between the coverage of the contract and
      occurrence of illnesses (as approximated by hospitalization) was not strong. The
      consideration of complex sampling in the probit estimations led to empirical
      evidence that does not indicate the presence of adverse selection, but which
      highlighted some interesting features of the relationship between the selected
      variables.

PMID- 20145969
TI  - Dissecting complex phenotypes using the genomics of twins.
AB  - Genetics in the post-genomic period is shifting from structural to functional
      genetics or genomics. Meanwhile, the use of twins is largely expanding from
      traditional heritability estimation for disease phenotypes to the study of both
      diseases and various molecular phenotypes, such as the regulatory phenotypes in
      functional genomics concerning gene expression and regulation, by engaging both
      classical twin design and marker-based gene mapping techniques in genetic
      epidemiology. New research designs have been proposed for making novel uses of
      twins in studying the molecular basis in the epigenetics of human diseases.
      Besides, twins not only serve as ideal samples for disease gene mapping using
      conventional genetic markers but also represent an excellent model for
      associating DNA copy number variations, a structural genetic marker, with human
      diseases. It is believed that, with the rapid development in biotechniques and
      new advances in bioinformatics, the unique samples of twins will make new
      contributions to our understanding of the nature and nurture in complex disease
      development and in human health. This paper aims at summarizing the new uses of
      twins in current genetic studies and suggesting novel proposes together with
      useful design and analytical strategies.

PMID- 20145971
TI  - Cytoplasmic inheritance of organelles in brown algae.
AB  - Brown algae, together with diatoms and chrysophytes, are a member of the
      heterokonts. They have either a characteristic life cycle of diplohaplontic
      alternation of gametophytic and sporophytic generations that are isomorphic or
      heteromorphic, or a diplontic life cycle. Isogamy, anisogamy and oogamy have been
      recognized as the mode of sexual reproduction. Brown algae are the characteristic
      group having elaborated multicellular organization within the heterokonts. In
      this study, cytoplasmic inheritance of chloroplasts, mitochondria and centrioles
      was examined, with special focus on sexual reproduction and subsequent zygote
      development. In oogamy, chloroplasts and mitochondria are inherited maternally.
      In isogamy, chloroplasts in sporophyte cells are inherited biparentally (maternal
      or paternal); however, mitochondria (or mitochondrial DNA) derived from the
      female gamete only remained during zygote development after fertilization.
      Centrioles in zygotes are definitely derived from the male gamete, irrespective
      of the sexual reproduction pattern. Female centrioles in zygotes are selectively
      broken down within 1-2 h after fertilization. The remaining male centrioles play
      a crucial role as a part of the centrosome for microtubule organization, mitosis,
      determination of the cytokinetic plane and cytokinesis, as well as for
      maintaining multicellularity and regular morphogenesis in brown algae.

PMID- 20145972
TI  - Review of cytological studies on cellular and molecular mechanisms of uniparental
      (maternal or paternal) inheritance of plastid and mitochondrial genomes induced
      by active digestion of organelle nuclei (nucleoids).
AB  - In most sexual organisms, including isogamous, anisogamous and oogamous
      organisms, uniparental transmission is a striking and universal characteristic of
      the transmission of organelle (plastid and mitochondrial) genomes (DNA). Using
      genetic, biochemical and molecular biological techniques, mechanisms of
      uniparental (maternal and parental) and biparental transmission of organelle
      genomes have been studied and reviewed. Although to date there has been no
      cytological review of the transmission of organelle genomes, cytology offers
      advantages in terms of direct evidence and can enhance global studies of the
      transmission of organelle genomes. In this review, I focus on the cytological
      mechanism of uniparental inheritance by "active digestion of male or female
      organelle nuclei (nucleoids, DNA)" which is universal among isogamous,
      anisogamous, and oogamous organisms. The global existence of uniparental
      transmission since the evolution of sexual eukaryotes may imply that the cell
      nuclear genome continues to inhibit quantitative evolution of organelles by
      organelle recombination.

PMID- 20145973
TI  - Analysis of wide-domain transcriptional regulation in solid-state cultures of
      Aspergillus oryzae.
AB  - Many filamentous fungi secrete considerable quantities of enzymes including
      protease, cellulase and xylanase, which are of major industrial importance. Over
      the past few decades, many of these fungal enzymes have been isolated and their
      relevant genes characterised. Solid-state fermentation (SSF), an ancient
      technique described as a fermentation process performed on non-soluble material
      whereby the material acts as a physical support and as a source of nutrients, is
      widely employed in the production of industrially important enzymes. Control
      mechanisms governing gene expression in SSF however, have been rarely studied.
      The influence of carbon and nitrogen sources on the production and
      transcriptional regulation of hydrolase enzymes secreted by an Aspergillus strain
      was investigated with the hope of expanding on the relatively small amount of
      knowledge regarding cellular control of gene expression. This study involved
      screening a collection of fungal strains for protease, cellulase and xylanase
      production under SSF conditions. From this, one fungal strain was then chosen for
      further analysis. Factors affecting the secretion of the hydrolase enzymes were
      optimised, and following this, the influence of nutritional supplementation on
      the production and transcriptional regulation of the enzymes was investigated.
      Real-time PCR techniques were used to assess the relative expression levels of
      genes encoding hydrolase activities and of the genes encoding regulatory elements
      such as AreA, PacC and CreA in an effort to identify possible transcriptional
      regulation mechanisms. The complexity of gene regulation under SSF conditions
      became apparent during the study, as other factors such as post-transcriptional
      regulation appeared to play a far greater role than previously imagined.

PMID- 20145974
TI  - Predicting the distribution of Vibrio spp. in the Chesapeake Bay: a Vibrio
      cholerae case study.
AB  - Vibrio cholerae, the causative agent of cholera, is a naturally occurring
      inhabitant of the Chesapeake Bay and serves as a predictor for other clinically
      important vibrios, including Vibrio parahaemolyticus and Vibrio vulnificus. A
      system was constructed to predict the likelihood of the presence of V. cholerae
      in surface waters of the Chesapeake Bay, with the goal to provide forecasts of
      the occurrence of this and related pathogenic Vibrio spp. Prediction was achieved
      by driving an available multivariate empirical habitat model estimating the
      probability of V. cholerae within a range of temperatures and salinities in the
      Bay, with hydrodynamically generated predictions of ambient temperature and
      salinity. The experimental predictions provided both an improved understanding of
      the in situ variability of V. cholerae, including identification of potential
      hotspots of occurrence, and usefulness as an early warning system. With further
      development of the system, prediction of the probability of the occurrence of
      related pathogenic vibrios in the Chesapeake Bay, notably V. parahaemolyticus and
      V. vulnificus, will be possible, as well as its transport to any geographical
      location where sufficient relevant data are available.

PMID- 20145975
TI  - A phase 1, multicenter, open-label study of the safety of two dose levels of a
      human monoclonal antibody to human alpha(v) integrins, intetumumab, in
      combination with docetaxel and prednisone in patients with castrate-resistant
      metastatic prostate cancer.
AB  - PURPOSE: We evaluated the safety and efficacy of intetumumab in combination with
      docetaxel in patients with castrate-resistant metastatic prostate cancer.
      Patients and methods In this phase 1, open-label, multicenter, nonrandomized
      study, 75 mg/m2 docetaxel was administered on Day 1 of each of nine 21-day
      treatment cycles and intetumumab 5 or 10 mg/kg was administered on Days 1, 8, and
      15 of Cycles 2 and 3 and on Day 1 of all subsequent cycles. The primary endpoint
      was the incidence of dose-limiting toxicities (DLTs) during Cycles 2 and 3.
      Secondary endpoints included serum prostate-specific antigen (PSA) response and
      objective response based on Response Evaluation Criteria in Solid Tumors
      (RECIST). RESULTS: Ten patients were treated (5 mg/kg n = 3, 10 mg/kg n = 7). No
      DLTs occurred. Most treatment-emergent adverse events (TEAEs) occurred in the 10
      mg/kg intetumumab group. Common TEAEs were neutropenia (10 mg/kg n = 6) and
      nausea (5 mg/kg n = 1, 10 mg/kg n = 5). Four 10-mg/kg-treated patients reported
      serious TEAEs; of these, only febrile neutropenia was considered probably
      intetumumab-related. In the 10-mg/kg group, four patients had a serum PSA
      response (two of whom responded within 3 months of treatment), one patient
      demonstrated partial tumor response for 11 weeks, and none had progressive
      disease at Cycle 9. No PSA or tumor response was observed in the 5-mg/kg group.
      CONCLUSIONS: Intetumumab was generally safe and well tolerated in combination
      with docetaxel, with a higher incidence of TEAEs in the 10 mg/kg dose cohort. The
      efficacy of 10 mg/kg intetumumab in combination with docetaxel appears to warrant
      further study.

PMID- 20145976
TI  - Contribution of bovine lactoferrin inter-lobe region to iron binding stability
      and antimicrobial activity against Staphylococcus aureus.
AB  - The investigation of the recombinant bovine lactoferrin-derived antimicrobial
      protein (rBLfA) demonstrates that the inter-lobe region of bovine lactoferrin
      contributes to iron binding stability and antimicrobial activity against
      Staphylococcus aureus. rBLfA containing N-lobe (amino acid residues 1-333) and
      inter-lobe region (residues 334-344) was expressed in Pichia pastoris at shaking
      flask and fermentor level. The recombinant intact bovine lactoferrin (rBLf) and N
      lobe (rBLfN) were expressed in the same system as control. The physical-chemical
      parameters of rBLfA, rBLfN and rBLf including amino acid residues, molecular
      weight, isoelectric point, net positive charge and instability index were
      computed and compared. The simulated tertiary structure and the calculated
      surface net charge showed that rBLfA maintained original structure and exhibited
      a higher cationic feature than rBLf and rBLfN. The three proteins showed
      different iron binding stability and antimicrobial activity. rBLfA released iron
      in the pH range of 7.0-3.5, whereas rBLfN lost its iron over the pH range of 7.0
      4.0 and iron release from rBLf occurred in the pH range of 5.5-3.0. However, the
      minimum inhibition concentration of rBLfA against S. aureus ATCC25923 was 6.5
      micromol/L, compared with 12.5 and 25 micromol/L that of rBLfN and rBLf,
      respectively. These results revealed that S. aureus was more sensitive to rBLfA
      than rBLfN and rBLf. It appeared that the strong cationic character of inter-lobe
      region related positively to the higher anti-S. aureus activity.

PMID- 20145978
TI  - Mechanical strength of extrusion freeformed calcium phosphate filaments.
AB  - Hydroxyapatite-tricalcium phosphate mixtures of various compositions were
      extruded by a solid free-forming process to form lattice structures to serve as
      hard tissue scaffolds. The unwelded filaments, sintered at temperatures from 1100
      to 1300 degrees C, had radii from 115 to 135 microm and were tested in three
      point flexural loading using a purpose-built fixture. Flexural strength ranged
      from 20 to 100 MPa depending on composition and sintering temperature. Weibull
      moduli up to 13 were obtained. Compositions with 50% or more tri-calcium
      phosphate did not develop strengths much above 40 MPa and the strength of most
      compositions fell when the sintering temperature exceeded 1250 degrees C.
      Multiple layer lattice structures were created and tested in compression.

PMID- 20145977
TI  - Are large wattles related to particular MHC genotypes in the male pheasant?
AB  - In sexually dimorphic species, partners can assess heritable mate quality by
      analyzing costly sexual ornaments in terms of their dimension and possibly of
      their symmetry. In vertebrates an important aspect of genetic quality is the
      efficiency of the immune system, and in particular the Major Histocompatibility
      Complex (MHC). If ornaments are honest advertisements of pathogen resistance
      (good genes), in line with the Hamilton-Zuk hypothesis, a correlation between
      ornament expression and MHC profiles should exist. We tested this hypothesis in
      the common pheasant Phasianus colchicus by comparing male ornament
      characteristics (wattle and spur size, and wattle fluctuating asymmetry) with a
      portion of exon 2 of the class IIB MHC genes containing 19 putative antigen
      recognition sites. A total of 8 new alleles was observed in the MHCPhco exon IIB.
      We found significant differences in the occurrence of MHC genotypes between males
      carrying large or small wattles. Homozygous genotypes predicted large wattle
      males more correctly than small wattle males. The association between the
      dimension of the spur and the occurrence of MHC genotypes was marginally
      significant, however, we did not find any significant association between MHC
      genotypes and asymmetry. Our results suggest that female pheasants may use the
      ornament size as a cue to evaluate male quality and thus choose males carrying
      particular MHC profiles.

PMID- 20145979
TI  - Nano-scale sliding contact deformation behaviour of enamel under wet and dry
      conditions.
AB  - The abrasion response of cross sectional areas of enamel was studied by sliding a
      rounded diamond conical nano-indenter tip across the surface. The nano-indenter
      tip (radius approximately 1,200 nm) was scanned over a specific squared area with
      a load of 400 microN. Two different environments were chosen: Hank's balanced
      salt solution (HBSS) and atmospheric laboratory condition. SEM (Scanning Electron
      Microscopy) and AFM (Atomic Force Microscopy) were used to characterize the final
      abraded areas. In addition, single scratches with linear incremented load were
      performed. The normal load and displacement data were utilized in a complementary
      manner to support the proposed deformation mechanisms. Greater orientation
      dependence for the case of the single scratches in relation to the abrasion tests
      was found. The latter results are discussed in terms of plastic deformation
      effects. The abrasion mechanisms were found to be the same for both wet and dry
      measurements and similar to that described in a previous study (Guidoni et al.,
      Wear 266:60-68, 2009; Guidoni, Nano-scale mechanical and tribological properties
      of mineralized tissues. PhD. Montan University Leoben, Leoben, Austria, 2008).
      However, scratch deformation under fluid measurements shows greater recovery
      effects and abrasion resistance.

PMID- 20145980
TI  - Inactivation of baculovirus by isoflavonoids on chickpea (Cicer arietinum) leaf
      surfaces reduces the efficacy of nucleopolyhedrovirus against Helicoverpa
      armigera.
AB  - Biological pesticides based on nucleopolyhedroviruses (NPVs) can provide an
      effective and environmentally benign alternative to synthetic chemicals. On some
      crops, however, the efficacy and persistence of NPVs is known to be reduced by
      plant specific factors. The present study investigated the efficacy of
      Helicoverpa armigera NPV (HearNPV) for control of H. armigera larvae, and showed
      that chickpea reduced the infectivity of virus occlusion bodies (OBs) exposed to
      the leaf surface of chickpea for at least 1 h. The degree of inactivation was
      greater on chickpea than that previously reported on cotton, and the mode of
      action is different from that of cotton. The effect was observed for larvae that
      consumed OBs on chickpea leaves, but it also occurred when OBs were removed after
      exposure to plants and inoculated onto artificial diet, indicating that
      inhibition was leaf surface-related and permanent. Despite their profuse
      exudation from trichomes on chickpea leaves and their low pH, organic acids
      primarily oxalic and malic acid-caused no inhibition. When HearNPV was incubated
      with biochanin A and sissotrin, however, two minor constituents of chickpea leaf
      extracts, OB activity was reduced significantly. These two isoflavonoids
      increased in concentration by up to 3 times within 1 h of spraying the virus
      suspension onto the plants and also when spraying only the carrier, indicating
      induction was in response to spraying and not a specific response to the HearNPV.
      Although inactivation by the isoflavonoids did not account completely for the
      level of effect recorded on whole plants, this work constitutes evidence for a
      novel mechanism of NPV inactivation in legumes. Expanding the use of biological
      pesticides on legume crops will be dependent upon the development of suitable
      formulations for OBs to overcome plant secondary chemical effects.

PMID- 20145981
TI  - Flavonoids have differential effects on glucose absorption in rats (Rattus
      norvegicus) and American robins (Turdis migratorius).
AB  - Mounting evidence suggests that small birds rely largely on non-mediated
      intestinal absorption of glucose through the paracellular pathway, while non
      flying mammals rely on mediated absorption across the enterocyte membranes by
      using glucose transporters SGLT-1 and GLUT-2. Relying on non-mediated transport
      of glucose may decrease its absorption rate at low glucose concentrations but may
      release small birds from the effects of glucose transport inhibitors. We
      evaluated transport by using flavonoids known to inhibit glucose transport in
      vitro. Quercetin, isoquercetrin, and phloridzin were tested in rats (Rattus
      norvegicus) and robins (Turdis migratirius), and naringenin, naringenin-7
      glucoside, genistein, epigallocatechin gallate (EGCG), and phloretin were used
      only in rats. By using a pharmacokinetic approach that involves serial blood
      collection and area under the curve calculations, we determined the
      bioavailability of 3-0-methyl D-glucose, the non-metabolized analogue of D
      glucose. Six of the eight flavonoids tested in rats significantly decreased the
      absorption of 3-0-methyl D-glucose, while none of the flavonoids tested in robins
      significantly decreased the bioavailability of 3-0-methyl D-glucose. We conclude
      that flavonoids effectively decrease glucose absorption in rats, which rely on
      mediated absorption of glucose, but that flavonoids do not have an effect in
      robins, which rely on non-mediated absorption of glucose.

PMID- 20145982
TI  - Isolation of a pyrazine alarm pheromone component from the fire ant, Solenopsis
      invicta.
AB  - Alarm pheromones in social insects are an essential part of a complex of
      pheromone interactions that contribute to the maintenance of colony integrity and
      sociality. The alarm pheromones of ants were among the first examples of animal
      pheromones identified, primarily because of the large amount of chemical produced
      and the distinctive responses of ants to the pheromone. However, the alarm
      pheromone of the fire ant, Solenopsis invicta, eluded identification for over
      four decades. We identified 2-ethyl-3,6-dimethylpyrazine as an alarm pheromone
      component of S. invicta. Worker fire ants detect the pyrazine alarm pheromone at
      30 pg/ml, which is comparable to alarm pheromone sensitivities reported for other
      ant species. The source of this alarm pheromone are the mandibular glands, which,
      in fire ants, are not well developed and contain only about 300 pg of the
      compound, much less than the microgram quantities of alarm pheromones reported
      for several other ant species. Female and male sexuals and workers produce the
      pyrazine, which suggests that it may be involved in fire ant mating flight
      initiation, as well as the typical worker alarm response. This is the first
      report of 2-ethyl-3,6-dimethylpyrazine from a Solenopsis species and the first
      example of this alkaloid functioning as an alarm pheromone.

PMID- 20145983
TI  - Water stress response of conventional and transgenic soybean plants monitored by
      chlorophyll a fluorescence.
AB  - Two soybean cultivars, one conventional and a glyphosate-tolerant (transgenic),
      were submitted to the water stress and the chlorophyll a fluorescence induced by
      UV light was monitored daily during 16 days. In this work, 40 pots in total, 20
      per cultivar were used in the investigation. Each cultivar was divided in two
      groups, the control group and the group submitted to the water stress. The stress
      response of the cultivars was monitored by red to far-red fluorescence ratio. The
      data indicate that the water stress induced the earliest changes on the
      fluorescence ratio and chlorophyll content for the conventional cultivar. In
      addition, a comparative analysis of the fluorescence ratios of the cultivars
      reveals that conventional plants have higher chlorophyll content than transgenic
      ones. This result might be useful in the development of methodologies able to
      distinguish conventional to transgenic apart.

PMID- 20145984
TI  - The effect of framing actuarial risk probabilities on involuntary civil
      commitment decisions.
AB  - Despite a proliferation of actuarial risk assessment instruments, empirical
      research on the communication of violence risk is scant and there is virtually no
      research on the consumption of actuarial risk assessment. Using a 2 * 3 Latin
      Square factorial design, this experiment tested whether decision-makers are
      sensitive to varying levels of risk expressed probabilistically and whether the
      framing of actuarial risk probabilities is consequential for commitment
      decisions. Consistent with research on attribute framing, in which describing an
      attribute in terms of its complement leads to different conclusions, this
      experiment found that the way actuarial risk estimates are framed leads to
      disparate commitment decisions. For example, risk framed as 26% probability of
      violence generally led decision-makers to authorize commitment, whereas the same
      risk framed in the complement, a 74% probability of no violence, generally led
      decision-makers to release. This result was most pronounced for moderate risk
      levels. Implications for the risk communication format debate, forensic practice
      and research are discussed.

PMID- 20145985
TI  - Assessing the violent offending and violent victimization overlap among
      discharged psychiatric patients.
AB  - Prior studies have documented linkages between mental disorder and both offending
      and victimization. However, few studies have examined the violent offending
      violent victimization overlap among mentally disordered individuals and none have
      examined the factors that are jointly related to their covariation. Here, we
      assess this overlap during the first ten weeks following hospital discharge among
      a large sample of psychiatric patients from three large cities. Findings indicate
      that: (1) violent offending and violent victimization show substantial
      covariation; (2) although each of the two outcomes were predicted by a few unique
      risk factors, several risk factors were similarly predictive of both outcomes;
      and (3) even after adjusting for demographic, clinical, and social risk factors,
      the correlation between violent offending and violent victimization remained
      robust. Implications for theory, research, and policy are highlighted.

PMID- 20145986
TI  - Randomized controlled caregiver mediated joint engagement intervention for
      toddlers with autism.
AB  - This study aimed to determine if a joint attention intervention would result in
      greater joint engagement between caregivers and toddlers with autism. The
      intervention consisted of 24 caregiver-mediated sessions with follow-up 1 year
      later. Compared to caregivers and toddlers randomized to the waitlist control
      group the immediate treatment (IT) group made significant improvements in
      targeted areas of joint engagement. The IT group demonstrated significant
      improvements with medium to large effect sizes in their responsiveness to joint
      attention and their diversity of functional play acts after the intervention with
      maintenance of these skills 1 year post-intervention. These are among the first
      randomized controlled data to suggest that short-term parent-mediated
      interventions can have important effects on core impairments in toddlers with
      autism. Clinical Trials #: NCT00065910.

PMID- 20145987
TI  - Effects of hypercapnia on the electroretinogram in sevoflurane and isoflurane
      anaesthetized dogs.
AB  - To evaluate the effects of induced hypercapnia on the electroretinogram (ERG) in
      beagle dogs anaesthetized with isoflurane and sevoflurane. Binocular, full-field
      flash photopic and scotopic ERGs were obtained from six healthy neutered female
      beagle dogs. In order to determine Vmax and the photopic negative response
      (PhNR), photopic ERG luminance-response curves were generated with 17 different
      light stimuli. Photopic flicker ERGs were obtained at 30-Hz temporal frequency.
      Scotopic ERGs were recorded after 35 min of dark adaptation. For all animals,
      this procedure was performed once in four different sessions: isoflurane + end
      tidal [CO(2)] at 35 mmHg +/- 3 mmHg (ISON), isoflurane + end-tidal [CO(2)] at 65
      mmHg +/- 3 mmHg (ISOH), sevoflurane + end-tidal [CO(2)] at 35 mmHg +/- 3 mmHg
      (SEVON), isoflurane + end-tidal [CO(2)] at 65 mmHg +/- 3 mmHg (SEVOH). In
      photopic conditions, b-wave amplitudes were significantly smaller in hypercapnic
      groups (ISON = 170.6 +/- 12.1 microV; ISOH = 132.6 +/- 24.9 microV; SEVON = 170.9
      +/- 14.4 microV; SEVOH = 130.2 +/- 22.8 microV). Similarly, in scotopic
      conditions, b-wave amplitudes were significantly decreased when CO(2) was
      increased (ISON = 89.4 +/- 14.7 microV; ISOH = 58.2 +/- 17.6 microV; SEVON = 93.4
      +/- 24.1 microV; SEVOH = 56.2 +/- 22.2 microV). Flicker peak times were
      significantly increased in hypercapnic groups (ISON = 25.9 +/- 0.4 ms; ISOH =
      27.7 +/- 1.2 ms; SEVON = 25.9 +/- 1.5 ms; SEVOH = 27.2 +/- 0.7 ms). Our results
      clearly indicate that induced hypercapnia significantly alters the genesis of the
      electroretinogram at level of ON-pathway and suggest that OFF-pathway is
      unaffected and that ERGs obtained from isoflurane or sevoflurane anaesthetized
      dogs are almost identical. Control of hypercapnia must be taken into
      consideration when ERGs are performed under inhaled anaesthesia in dogs.

PMID- 20145988
TI  - Influence of pupil size and other test variables on visual function assessment
      using visual evoked potentials in normal subjects.
AB  - The purpose of this study was to assess the influence of pupil size and optical
      blur on measurements obtained with isolated-check visual evoked potential
      (icVEP). Two stimulus conditions of icVEP, +15 and -15% contrasts, were studied
      in normal subjects with normal (N), miotic (M), and dilated (D) pupils. The
      effects of optical blur were studied in subjects with normal pupil. Response to
      visual stimuli was quantified by a signal-to-noise (SNR) ratio. In 30 normal
      subjects, the mean age was 26.0 +/- 3.4 years. Mean pupil diameters were N = 4.2
      +/- 0.6 mm, M = 2.7 +/- 0.6 mm, and D = 7.3 +/- 0.9 mm. For both +15 and -15%
      contrast levels, mean SNR values were reduced for dilated and constricted pupils
      when compared with normal pupils. Mean SNR values for optical blur with a +2 or
      +3 diopter lens placed over the distance correction were reduced when compared
      with SNR measurements obtained with best-corrected visual acuity under both +15
      and -15% contrast levels. Statistical significance was found in comparisons of N
      versus M (P < 0.001) and N versus D (P = 0.002) for +15 and -15% contrast
      conditions, respectively. No statistical difference was seen for M versus D (P = 
      0.435). The effect of optical blur was statistically significant when compared to
      the normal pupils with best-corrected vision (P < 0.001). No statistically
      significant difference was found comparing +2 and +3 diopters lenses for optical
      blur testing. Visual evoked potential values are influenced by pupillary
      constriction and dilation, as well as optical blur. When obtaining icVEP
      measurements, the influence of pupil size and optical blur should be kept in mind
      for accurate interpretations.

PMID- 20145989
TI  - Familial resemblance for loneliness.
AB  - Social isolation and loneliness in humans have been associated with physical and
      psychological morbidity, as well as mortality. This study aimed to assess the
      etiology of individual differences in feelings of loneliness. The genetic
      architecture of loneliness was explored in an extended twin-family design
      including 8,683 twins, siblings and parents from 3,911 families. In addition, 917
      spouses of twins participated. The presence of assortative mating, genetic non
      additivity, vertical cultural transmission, genotype-environment (GE) correlation
      and interaction was modeled. GE interaction was considered for several
      demographic characteristics. Results showed non-random mating for loneliness. We
      confirmed that loneliness is moderately heritable, with a significant
      contribution of non-additive genetic variation. There were no effects of vertical
      cultural transmission. With respect to demographic characteristics, results
      indicated that marriage, having offspring, more years of education, and a higher
      number of siblings are associated with lower levels of loneliness. Interestingly,
      these effects tended to be stronger for men than women. There was little evidence
      of changes in genetic architecture as a function of these characteristics. We
      conclude that the genetic architecture of loneliness points to non-additive
      genetic influences, suggesting it may be a trait that was not neutral to
      selection in our evolutionary past. Sociodemographic factors that influence the
      prevalence of loneliness do not affect its genetic architecture.

PMID- 20145990
TI  - Workforce development and the organization of work: the science we need.
AB  - The industrialization of health care, underway for several decades, offers
      instructive guidance and models for speeding access of children and families to
      clinically and cost effective preventive, treatment, and palliative
      interventions. This industrialization--i.e., the systematized production of goods
      or services in large-scale enterprises--has the potential to increase the value
      and effects of care for consumers, providers, and payers (Hayes and Gregg in
      Integrated behavioral healthcare: Positioning mental health practice with
      medical/surgical practice. Academic Press, San Diego, 2001), and to generate
      efficiencies in care delivery, in part because workforce responsibilities become
      more functional and differentiated such that individuals with diverse educational
      and professional backgrounds can effectively execute substantive clinical roles
      (Rees in Clin Exp Dermatol, 33, 39-393, 2008). To date, however, the models
      suggested by this industrialization have not been applied to children's mental
      health services. A combination of policy, regulatory, fiscal, systemic, and
      organizational changes will be needed to fully penetrate the mental health and
      substance abuse service sectors. In addition, problems with the availability,
      preparation, functioning, and status of the mental health workforce decried for
      over a decade will need to be addressed if consumers and payers are to gain
      access to effective interventions irrespective of geographic location, ethnic
      background, or financial status. This paper suggests that critical knowledge gaps
      exist regarding (a) the knowledge, skills, and competencies of a workforce
      prepared to deliver effective interventions; (b) the efficient and effective
      organization of work; and (c) the development and replication of effective
      workforce training and support strategies to sustain effective services. Three
      sets of questions are identified for which evidence-based answers are needed.
      Suggestions are provided to inform the development of a scientific agenda to
      answer these questions.

PMID- 20145992
TI  - Extremely low-frequency electromagnetic fields exposure and female breast cancer
      risk: a meta-analysis based on 24,338 cases and 60,628 controls.
AB  - Exposure to extremely low-frequency electromagnetic fields (ELF-EMF) has been
      suggested to increase female breast cancer risk; however, the data have been
      inconclusive. In order to derive a more precise estimation of the relationship, a
      meta-analysis was performed. Medline, PubMed, Embase, the Cochrane Library and
      Web of Science were searched. Crude ORs with 95% CIs were used to assess the
      strength of association between ELF-EMF exposure and female breast cancer risk. A
      total of 15 studies published over the period 2000 to 2009 including 24,338 cases
      and 60,628 controls were involved in this meta-analysis. The results showed no
      significant association between ELF-EMF exposure and female breast cancer risk in
      total analysis (OR = 0.988, 95% CI = 0.898-1.088) and in all the subgroup
      analyses by exposure modes, menopausal status, and estrogen receptor status. This
      result is in accordance with the previous meta-analysis carried out by Erren in
      2000. In conclusion, this meta-analysis suggests that ELF-EMF exposure has no
      association with the susceptibility of female breast cancer.

PMID- 20145993
TI  - Random-walk model simulation of air pollutant dispersion in atmospheric boundary
      layer in China.
AB  - In this study, the land-sea breeze circulation model coupled with a random-walk
      model is developed by the analysis of the formation and the mechanism of the land
      sea breeze. Based on the data of the land-sea circulation in Dalian, China, the
      model simulated the diurnal variation of pressure, flow, temperature, and
      turbulent kinetic energy field and also provides a basis for solving the air
      pollutant concentration in the land-sea breeze circulation so as to estimate the
      economic cost attributable to the atmospheric pollution. The air pollutant
      concentration in the background of land-sea circulation is also simulated by a
      Gaussian dispersion model, and the results revealed that the land-sea circulation
      model coupled with the random-walk model gives a reasonable description of air
      pollutant dispersion in coastal areas.

PMID- 20145991
TI  - Losartan improved respiratory function and coenzyme Q content in brain
      mitochondria of young spontaneously hypertensive rats.
AB  - Increased production of free radicals and impairment of mitochondrial function
      are important factors in the pathogenesis of hypertension. This study examined
      the impact of hypertension on mitochondrial respiratory chain function, coenzyme
      Q(9) (CoQ(9)), coenzyme Q(10) (CoQ(10)), and alpha-tocopherol content in brain
      mitochondria, and the effect of blockade of angiotensin II type 1 receptors
      (AT1R) in the prehypertensive period on these parameters. In addition, blood
      pressure, heart and brain weight to body weight ratios, and the geometry of the
      basilar artery supplying the brain were evaluated. In the 9th week blood pressure
      and heart weight/body weight ratio were significantly increased and brain
      weight/body weight ratio was significantly decreased in spontaneously
      hypertensive rats (SHR) when compared to Wistar rats (WR). The cross-sectional
      area of the basilar artery was increased in SHR. Glutamate-supported respiration,
      the rate of ATP production, and concentrations of CoQ(9), CoQ(10), and alpha
      tocopherol were decreased in SHR. The succinate-supported function and cytochrome
      oxidase activity were not changed. The treatment of SHR with losartan (20
      mg/kg/day) from 4th to 9th week of age exerted preventive effect against
      hypertension, heart and arterial wall hypertrophy, and brain weight/body weight
      decline. After the therapy, the rate of ATP production and the concentration of
      CoQ increased in comparison to untreated SHR. The impairment of energy production
      and decreased level of lipid-soluble antioxidants in brain mitochondria as well
      as structural alterations in the basilar artery may contribute to increased
      vulnerability of brain tissue in hypertension. Long-term treatment with AT1R
      blockers may prevent brain dysfunction in hypertension.

PMID- 20145994
TI  - Use of object-oriented classification and fragmentation analysis (1985-2008) to
      identify important areas for conservation in Cockpit Country, Jamaica.
AB  - Forest fragmentation is one of the most important threats to global biodiversity,
      particularly in tropical developing countries. Identifying priority areas for
      conservation within these forests is essential to their effective management.
      However, this requires current, accurate environmental information that is often
      lacking in developing countries. The Cockpit Country, Jamaica, contains forests
      of international importance in terms of levels of endemism and overall diversity.
      These forests are under severe threat from the prospect of bauxite mining and
      other anthropogenic disturbances. In the absence of adequate, up-to-date
      ecological information, we used satellite remote sensing data and fragmentation
      analysis to identify interior forested areas that have experienced little or no
      change as priority conservation sites. We classified Landsat images from 1985,
      1989, 1995, 2002, and 2008, using an object-oriented method, which allowed for
      the inclusion of roads. We conducted our fragmentation analysis using metrics to
      quantify changes in forest patch number, area, shape, and aggregation.
      Deforestation and fragmentation fluctuated within the 23-year period but were
      mostly confined to the periphery of the forest, close to roads and access trails.
      An area of core forest that remained intact over the period of study was
      identified within the largest forest patch, most of which was located within the
      boundaries of a forest reserve and included the last remaining patches of closed
      broadleaf forest. These areas should be given highest priority for conservation,
      as they constitute important refuges for endemic or threatened biodiversity.
      Minimizing and controlling access will be important in maintaining this core.

PMID- 20145995
TI  - Polycyclic aromatic hydrocarbons in the atmosphere of Shanghai, China.
AB  - Shanghai is the largest industrial and commercial city in China, and its air
      quality has been concerned for several years. However, scarce study had been made
      on the seasonal levels of atmospheric polycyclic aromatic hydrocarbons (PAHs),
      together with their gas-particle partitioning and potential emission sources.
      Based on an intensive sampling campaign at urban and suburban areas in Shanghai
      during four seasons of 2005-2006, this study presented the measurement of PAH
      concentrations in both particulate and gaseous phases, as well as seasonal and
      spatial variability. The results showed that the annual PAH levels (gas +
      particle) were 167 +/- 109 ng m-3 at the urban site and 216 +/- 86.5 ng m-3 at
      the suburban site. Gaseous PAHs (>70%) dominated the total PAH mass at both
      sites, while particulate PAHs contributed more than 90% of the toxic power
      according to benzo(a)pyrene-equivalent carcinogenic parameter. Different seasonal
      trend of PAH concentrations was observed between the two sites, and it may be
      explained by complicated factors such as sampling heights, local/regional
      emission sources, and climatic conditions. The gas-particle partitioning of PAHs
      in all samples was calculated, and strong linear correlations between log K (p)
      and log P(L) degrees  were observed, with shallower slopes (m(r)) at the suburban
      site than the urban one and in warm season than the cold months, indicating the
      different equilibrium conditions of PAHs in spatial and seasonal scales in
      Shanghai. The slope (m(r) = - 0.96) and correlation coefficient (R2 = 0.81) for
      four-ring PAHs were closest to theoretical equilibrium conditions among compounds
      with various aromatic rings. Finally, the potential PAH sources were estimated
      based on principal factor analysis with multiple linear regressions. Ground
      volatilization dominated the PAH pollutions at both sites, while vehicles and
      coal consumption were the other main emission sources, which totally contributed
      32.0% (suburban) to 49.2% (urban) of PAH mass in Shanghai atmosphere. The effects
      of wood and biomass burning were also detected, but their contributions to PAHs
      were negligible.

PMID- 20145997
TI  - Spectrophotometric determination of platinum(IV) in alloys, complexes,
      environmental, and pharmaceutical samples using 4-[N,N-(diethyl)amino]
      benzaldehyde thiosemicarbazone.
AB  - 4-[N,N-(Diethyl)amino] benzaldehyde thiosemicarbazone (DEABT) is proposed as an
      analytical reagent for the spectrophotometric determination of platinum(IV). The
      DEABT forms 1:2 yellow complex with Pt(IV), which is sparingly soluble in water
      and completely soluble in water-ethanol-DMF medium. The Pt(IV)-DEABT complex
      shows maximum absorbance at 405 nm. Beer's law is valid up to 7.80 MUg cm(-3),
      and optimum concentration range for the determination of platinum(IV) is 0.48
      7.02 MUg cm(-3). The molar absorptivity and Sandell's sensitivity of the method
      are found to be 1.755 * 10(4) dm(3) mol(-1) cm(-1) and 0.0012 MUg cm(-2),
      respectively. The relative error and coefficient of variation (n=6) for the
      method does not exceed +/- 0.43% and 0.35%, respectively. Since the method
      tolerates a number of metal ions commonly associated with platinum, it can be
      employed for the determination of platinum in environmental samples,
      pharmaceutical samples, alloys, catalysts, and complexes. The method is rapid as
      the Pt(IV)-DEABT complex is soluble in water-ethanol-DMF medium and not requiring
      any time consuming extraction method for the complex.

PMID- 20145996
TI  - Dietary exposure of three passerine species to PCDD/DFs from the Chippewa,
      Tittabawassee, and Saginaw River floodplains, Midland, Michigan, USA.
AB  - Dietary exposure of house wrens (Troglodytes aedon), tree swallows (Tachycineta
      bicolor), and eastern bluebirds (Sialia sialis) to polychlorinated dibenzofurans
      (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) near Midland, Michigan
      (USA) was evaluated based on site-specific data, including concentrations of
      residues in bolus samples and individual invertebrate orders and dietary
      compositions by study species. Site-specific dietary compositions for the three
      species were similar to those reported in the literature, but differed in their
      relative proportions of some dietary items. Oligocheata (non-depurated) and
      Brachycera (Diptera) contained the greatest average concentrations of
      SigmaPCDD/DFs of the major site-specific dietary items collected via food web
      based sampling. Average ingestion values of SigmaPCDD/DFs from site-specific
      bolus-based and food web-based dietary concentrations for nestlings at study
      areas (SAs) were 6- to 20-fold and 2- to 9-fold greater than at proximally
      located reference areas (RAs), respectively. Average ingestion values of total
      2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ(WHO - Avian)) from site
      specific bolus-based and food web-based dietary concentrations for nestlings at
      SAs were 31- to 121-fold and 9- to 64-fold greater than at proximally located
      RAs, respectively. Estimates of SigmaPCDD/DFs and TEQ(WHO - Avian) tissue
      concentrations based on nestling dietary exposures were greater than those
      measured. Plausible explanations include nestling metabolism of 2,3,7,8
      tetrachlorodibenzofuran and assimilation rates of less than the 70% assumed to
      occur over the nestling growth period. Profiles of the relative concentrations of
      individual PCDD/DF congeners in samples of invertebrates and bolus at SAs on the
      Tittabawassee River downstream of the source of contamination were dominated by
      1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (22% to 44%) and 2,3,7,8
      tetrachlorodibenzofuran (18% to 50%).

PMID- 20145998
TI  - Controlled embryoid body formation via surface modification and avidin-biotin
      cross-linking.
AB  - Cell-cell interaction is an integral part of embryoid body (EB) formation
      controlling 3D aggregation. Manipulation of embryonic stem (ES) cell interactions
      could provide control over EB formation. Studies have shown a direct relationship
      between EB formation and ES cell differentiation. We have previously described a
      cell surface modification and cross-linking method for influencing cell-cell
      interaction and formation of multicellular constructs. Here we show further
      characterisation of this engineered aggregation. We demonstrate that engineering
      accelerates ES cell aggregation, forming larger, denser and more stable EBs than
      control samples, with no significant decrease in constituent ES cell viability.
      However, extended culture >/=5 days reveals significant core necrosis creating a
      layered EB structure. Accelerated aggregation through engineering circumvents
      this problem as EB formation time is reduced. We conclude that the proposed
      engineering method influences initial ES cell-ES cell interactions and EB
      formation. This methodology could be employed to further our understanding of
      intrinsic EB properties and their effect on ES cell differentiation.

PMID- 20145999
TI  - TVT vs. TOT: a comparison in terms of continence results, complications and
      quality of life after a median follow-up of 48 months.
AB  - AIM: To compare the tension-free vaginal tape (TVT) and obturator tape (TOT)
      procedures in terms of continence results, complications and quality of life
      after a median follow-up of 48 months. PATIENTS AND METHODS: Two hundred and
      eight female patients suffering from urodynamically proven urinary incontinence
      underwent TVT or TOT. The clinicopathologic parameters of the patients included
      age, body mass index, type of incontinence, onset of incontinence, previous
      pelvic surgery, parity, menopausal statement, perioperative and postoperative
      complications and outcome in terms of continence and quality of life. RESULTS:
      TVT was performed on 48.6% of patients and TOT on 51.4%. The median age was 63.4
      and median follow-up period was 48 months. Prior to surgery, stress urinary
      incontinence (SUI) was diagnosed in 75.7% of patients and mixed incontinence (SUI
      and urge incontinence) with a predominant SUI in 24.3%. An objective cure rate in
      patients who underwent TOT was observed in 77.7% of cases and in those who
      underwent TVT in 81%. The quality of life improved in 80% of cases. There was no
      significant difference between the procedures in terms of continence results and
      quality of life. The rate of the complications was significantly higher with the
      TVT procedure when compared to that of the TOT procedure. CONCLUSIONS: Although
      there were no significant differences between the two types of procedures in
      terms of continence results and quality of life, the TOT procedure demonstrates
      significantly better results in terms of the rate of complications, making it, if
      indicated, our first choice.

PMID- 20146000
TI  - Community knowledge, attitudes, and beliefs towards depression in the state of
      Penang, Malaysia.
AB  - This study was intended to evaluate the mental health literacy vis-a-vis
      depression among inhabitants of Penang state in North Malaysia. Using a clustered
      random sampling method, 1,855 respondents were approached to participate in the
      survey. A total of 1,149 respondents actually participated, for a 61.9% response
      rate. Face to face interviews were then conducted using a pre-validated 21-item
      questionnaire. The mean age of the respondents was 30 years (SD +/-11.5). The
      majority (n = 884; 76.9%) could recognize three or more symptoms of depression.
      Chinese and/or female respondents performed the best in this domain. Respondents
      with a personal experience of depression displayed a significantly better
      knowledge of symptoms of and therapies for depression than those who did not (t =
      -35.745, P = <0.001). Overall, a moderate knowledge level of the symptoms of
      depression and a cursory knowledge towards therapy were observed among the
      general population in Penang. Notably, respondents were generally inclined
      towards the use of alternative medicine. The study suggests that strong beliefs
      in alternative and traditional medicines could undermine the respondents'
      willingness and ability to seek evidence-based mental health care.

PMID- 20146001
TI  - The release of microparticles by Jurkat leukemia T cells treated with
      staurosporine and related kinase inhibitors to induce apoptosis.
AB  - Microparticles (MPs) are small membrane-bound vesicles released from cells
      undergoing activation or cell death. These particles display potent biological
      activities that can impact on physiologic and pathologic processes. Previous
      studies with the Jurkat T leukemia cell line demonstrated that staurosporine
      (STS) induces the release of MPs as cells undergo apoptosis. To investigate
      further this process, we tested the effects of STS, its analogue, 7
      hydroxystaurosporine (UCN-01), and other protein kinase C (PKC) and cyclin
      dependent kinase (CDK) inhibitors. FACS analysis was used to assess MP release.
      Results of these studies indicate that STS and UCN-01 induce MP release by Jurkat
      cells; in contrast, other PKC and CDK inhibitors failed to induce comparable
      release, suggesting that release does not result from simple inhibition of either
      kinase alone. Time course experiments indicated that STS-induced particle release
      occurred as early as 2 h after treatment, with the early release MPs displaying
      low levels of binding of annexin V and propidium iodide (PI). Early-release MPs,
      however, matured in culture to an annexin V- and PI-positive phenotype. Together,
      these results indicate that STS and UCN-01 induce MPs that are phenotypically
      distinct and reflect specific patterns of kinase inhibition during apoptosis.

PMID- 20146002
TI  - Low-dose CT and cardiac MR for the diagnosis of coronary artery disease: accuracy
      of single and combined approaches.
AB  - To prospectively compare the diagnostic performance of low-dose computed
      tomography coronary angiography (CTCA) and cardiac magnetic resonance imaging
      (CMR) and combinations thereof for the diagnosis of significant coronary
      stenoses. Forty-three consecutive patients with known or suspected coronary
      artery disease underwent catheter coronary angiography (CA), dual-source CTCA
      with prospective electrocardiography-gating, and cardiac CMR (1.5 Tesla). The
      following tests were analyzed: (1) low-dose CTCA, (2) adenosine stress-rest
      perfusion-CMR, (3) late gadolinium enhancement (LGE), (4) perfusion-CMR and LGE,
      (5) low-dose CTCA combined with perfusion-CMR, (5) low-dose CTCA combined with
      late gadolinium-enhancement, (6) low-dose CTCA combined with perfusion-CMR and
      LGE. CA served as the standard of reference. CA revealed >50% diameter stenoses
      in 68/129 (57.7%) coronary arteries in 29/43 (70%) patients. In the patient-based
      analysis, sensitivity, specificity, NPV and PPV of low-dose CTCA for the
      detection of significant stenoses were 100, 92.9, 100 and 96.7%, respectively.
      For perfusion-CMR and LGE, sensitivity, specificity, NPV, PPV, and accuracy were
      89.7, 100, 82.4, and 100%, respectively. In the artery-based analysis,
      sensitivity and NPV of low-dose CTCA was significantly (P < 0.05) higher than
      that of perfusion-CMR and LGE. All combinations of low-dose CTCA and perfusion
      CMR and/or LGE did not improve the diagnostic performance when compared to low
      dose CTCA alone. Taking CA as standard of reference, low-dose CTCA outperforms
      CMR with regard to sensitivity and NPV, whereas CMR is more specific and has a
      higher PPV than low-dose CTCA.

PMID- 20146003
TI  - Automated analysis of four-dimensional magnetic resonance images of the human
      aorta.
AB  - The purpose of the study was to demonstrate the accuracy and clinical utility of
      an automated method of image analysis of 4D (3D + time) magnetic resonance (MR)
      imaging of the human aorta. Serial MR images of the entire thoracic aorta were
      acquired on 32 healthy individuals. Graph theory based segmentation was applied
      to the images and cross sectional area (CSA) was determined for the entire length
      of thoracic aorta. Mean CSA was compared between the 3 years. CSA values at the
      level of sinuses of Valsalva and sino-tubular junction were used to calculate
      average diameters for comparison to Roman-Devereux norms. A robust automated
      segmentation method was developed that accurately reproduced CSA measurements for
      the entire length of thoracic aorta in serially acquired scans with a 1% error
      compared to expert tracing. Calculated aortic root diameters based on CSA
      correlated with Roman-Devereux norms. Mean CSA for the aortic root agreed well
      with previously published manually derived values. Automated analysis of 4D MR
      images of the thoracic aorta provides accurate and reproducible results for CSA
      in healthy human subjects. The ability to simultaneously analyze the entire
      length of thoracic aorta throughout the cardiac cycle opens the door to the
      calculation of novel indices of aortic biophysical properties. These novel
      indices may lead to earlier detection of patients at risk for adverse events.

PMID- 20146004
TI  - Trap induction and trapping in eight nematode-trapping fungi (Orbiliaceae) as
      affected by juvenile stage of Caenorhabditis elegans.
AB  - This study measured trap induction and trapping on agar disks as affected by
      juvenile stages (J1, J2, J3, and J4) of the nematode Caenorhabditis elegans and
      by species of nematode-trapping fungi. Eight species of nematode-trapping fungi
      belonging to the family Orbiliaceae and producing four kinds of traps were
      studied: adhesive network-forming Arthrobotrys oligospora, A. vermicola, and A.
      eudermata, constricting ring-forming Drechslerella brochopaga, and Dr.
      stenobrocha, adhesive column-forming Dactylellina cionopaga, and adhesive knob
      forming Da. ellipsospora, and Da. drechsleri. The number of traps induced
      generally increased with increasing juvenile stages of C. elegans. The ability to
      capture the juveniles tended to be similar among isolates that produced the same
      kind of trap but differed among species that produced different kinds of traps.
      Trapping by Dr. stenobrocha and Da. cionopaga was correlated with trap number and
      with juvenile stage. A. oligospora and A. vermicola respectively captured more
      than 92 and 88% of the J1, J3, and J4 but captured a lower percentage of J2. The
      knob-producing isolates captured more younger than elder juveniles. Partial
      correlation analyses demonstrated that the trap induction of the most fungal
      species positively correlated with the juvenile size and motility, which was
      juvenile stage dependent. Overall, trap induction and trapping correlated with C.
      elegans juvenile stage (size and motility) in six species of trapping fungi.

PMID- 20146005
TI  - Clinical significance of miR-221 and its inverse correlation with p27Kip1 in
      hepatocellular carcinoma.
AB  - The aim of the present study is to explore possible role of miR-221 in the
      pathogenesis of HCC. Matched HCC and adjacent non-cancerous samples were assayed
      for the expression of miR-221 and three G1/S transition inhibitors: p27(Kip1),
      p21(WAF1/Cip1)and TGF-beta1 by in situ hybridization and immunohistochemistry
      respectively. p27(Kip1) is one of miR-221's proven targets. Real time qRT-PCR was
      used to investigate miR-221 and p27(Kip1) transcripts in different clinical
      stages. Western blotting was used to analyze the expression levels of p27(Kip1)
      protein in different clinical stages. In result, miR-221 and TGF-beta1 are
      frequently up-regulated in HCC, while p27(Kip1) and p21(WAF1/Cip1) proteins are
      frequently down-regulated. Moreover, miR-221 and p27(Kip1)'s expression
      correlated with metastasis and miR-221's expression also correlated with tumor
      size. Both of p21(WAF1/Cip1)and TGF-beta1's expression correlated with tumor
      differentiations. miR-221's upregulation and p27(Kip1)'s downregulation were
      significantly associated with tumor stages and metastasis. In conclusion, miR-221
      is important in tumorigenesis of HCC, possibly by specifically down-regulating
      p27(Kip1), a cell-cycle inhibitor. These results indicate miR-221 as a new
      therapeutic target in HCC.

PMID- 20146006
TI  - Sp1 polymorphism in collagen I alpha1 gene is associated with osteoporosis in
      lumbar spine of Mexican women.
AB  - The Sp1 binding site polymorphism in collagen type I alpha 1 gene (COLIA1) has
      been associated with osteoporosis (OP) and bone mineral density (BMD). The aim of
      this study was to explore the association of this polymorphism with OP and BMD in
      the Mexican population by polymerase chain reaction and restriction fragment
      length polymorphism (PCR-RFLP) procedure. Allelic and genotypic frequencies from
      the Sp1 polymorphism were determined in 100 women with OP, 100 women without OP
      and 500 subjects from general Mexican population (GMP). Distribution of Sp1
      polymorphism was in Hardy-Weinberg equilibrium. In spite of population structure
      due to racial mix in Mexican population, associations with OP were demonstrated.
      The frequency of "s" allele was significantly higher in women with OP (35%) than
      in women without OP (11%; P < 0.00001). Interestingly, "ss" genotype, was
      exclusive of women with OP and was associated with low BMD (0.588 +/- 0.077
      g/cm(2)) in contrast to "SS" genotype (0.733 +/- 0.039 g/cm(2); P = 0.0001). This
      work confirms the association of Sp1 polymorphism with low BMD and OP in Mexican
      population and make sure to use Sp1 as a genetic marker for OP in our population.

PMID- 20146008
TI  - Psychometric properties of the EQ-5D in a study of people with mild to moderate
      dementia.
AB  - PURPOSE: Due to their cognitive impairment, the health-related quality of life
      (HRQoL) of patients with dementia is often rated by proxies. This study aims to
      analyse the psychometric properties of the EQ-5D applied to patients with mild to
      moderate dementia and their family caregivers. METHODS: Three hundred and ninety
      patients and their caregivers were asked to assess the patients' HRQoL using the
      EQ-5D. The German population-based time trade-off values were used to calculate
      utility weights. Acceptance, discriminative ability, construct validity, inter
      rater agreement and responsiveness were tested. Factors that could have an impact
      on inter-rater agreement were analysed using a multivariate regression. RESULTS:
      Five per cent of patients did not fill out the EQ-5D. The response rate of
      caregivers and of patients with mild dementia was higher than that of patients
      with moderate dementia. There were no floor or ceiling effects. The test results
      of the caregivers concerning construct validity and responsiveness were better
      than those of the patients. The inter-rater reliability was not satisfactory
      either on the dimension level or on the utility score level. Caregivers gave the
      patients' HRQoL significantly lower ratings than did the patients themselves.
      Better abilities of the patient to perform activities of daily living and a lower
      subjective burden of the caregiver were associated with a higher inter-rater
      agreement. CONCLUSIONS: The study showed that the EQ-5D is especially applicable
      to patients with mild dementia and their caregivers as proxies. However, there
      are important differences between patient and proxy ratings, even in cases of
      mild dementia, at the dimension level as well as utility score level, which
      should be considered in the interpretation of quality of life scores.

PMID- 20146007
TI  - Relationship of quality of life to dispositional optimism, health locus of
      control and self-efficacy in older subjects living in different environments.
AB  - PURPOSE: To describe the relationship of dispositional optimism, health locus of
      control and self-efficacy to quality of life (QOL) in older subjects differing in
      level of disability and institutionalisation. METHODS: The study was conducted in
      the three groups of subjects aged > or = 65: 110 relatively healthy community
      dwelling elderly, 102 independent elders who voluntarily decided to live in
      veteran home and 112 inhabitants of a long-term care home. Life orientation test
      revised (LOT-R), multidimensional health locus of control (MHLC) and generalised
      self-efficacy scale (GSES) together with a multidimensional assessment were
      performed with each subject. QOL was assessed using the Euroqol 5D questionnaire,
      the Nottingham health profile and the satisfaction with life scale (SWLS).
      RESULTS: QOL generally decreased with growing level of dependence and
      institutionalisation. LOT-R, MHLC and GSES were important and independent
      correlates of QOL in all three environments of older subjects. The relationship
      of education, smoking habit, physical activity, strength and mobility measures to
      psychological characteristics was different in the three groups of elders. LOT-R,
      MHLC Powerful Others, MHLC Chance and GSES were the most important QOL correlates
      in veteran home group, while MHLC Internal was most significant in long-term care
      home inhabitants. CONCLUSIONS: Data of this cross-sectional study suggests that
      the veteran home elderly, as a group 'in transition' between community and
      institution, should be the first target of psychological preventive and health
      promoting measures aimed at improving QOL in older population.

PMID- 20146009
TI  - Assessing the use of health-related quality of life measures in the routine
      clinical care of lung-transplant patients.
AB  - PURPOSE: This randomized controlled clinical trial examined the usefulness of
      including an assessment of health-related quality of life (HRQL) in the routine
      clinical care of lung-transplant patients. We hypothesized that the inclusion of
      HRQL in routine clinical care would improve patient-clinician communication,
      affect clinical management, and improve patients' HRQL. METHODS: At the
      outpatient clinic, University of Alberta Hospital, patients were randomly
      assigned to intervention (completion of Health Utilities Index Mark 2 (HUI2) and
      Mark 3 (HUI3) on touch-screen computer with feedback to clinicians) and control
      group (completion of HUI2 and HUI3 on touch-screen computer without feedback).
      Feedback involved a graphical representation included in patients' chart. All
      clinical encounters were audio-taped. Changes in clinical management (medication
      changes, number of referrals and test ordered) were summed to produce an overall
      management composite. At the end of every visit, patients completed the EQ-5D.
      RESULTS: Two hundred and thirteen patients were randomized (108 to intervention
      and 105 to control groups). There were statistically significant differences
      between the groups in mean number of issues discussed per encounter (P = 0.003;
      Cohen's d = 0.03) and mean management composite score (P = 0.001; Cohen's d =
      0.41). EQ-5D index was not statistically significant different between the groups
      (P = 0.48). CONCLUSIONS: We detected very small effects on patient-clinician
      communication and small effects on patient management, without detecting
      improvement in patient outcome.

PMID- 20146010
TI  - Retracted Article: Association of physical fitness with health-related quality of
      life in Finnish young men.

PMID- 20146011
TI  - Potential release of aluminum and other metals by food-grade aluminum foil used
      for skin allograft cryo preservation.
AB  - Since 1991, the skin bank of the Queen Astrid Military Hospital uses food-grade
      aluminum foil as a primary support for storing cryo preserved human donor skin
      (511 donors). The possible release of heavy metals into the cryo preservation
      media (30% (v/v) glycerol in physiological water) and the possible impact this
      release could have on the quality of the cryo preserved donor skin was evaluated.
      Aluminum was the principal detection target. Possible contaminants of the
      aluminum foil as such (arsenic, cadmium, chromium and lead) were also
      investigated. The evaluation was set up after a Belgian Competent Authority
      inspection remark. Aluminum was detected at a concentration of 1.4 mg/l, arsenic
      and lead were not detected, while cadmium and chromium were detected in trace
      element quantities. An histological analysis revealed no differences between cryo
      preserved and fresh donor skin. No adverse reactions in patients, related to the
      presence of aluminum or heavy metal traces, were reported since the introduction
      of the cryo preserved donor skin in our burn wound centre.

PMID- 20146012
TI  - Interaction of hippocampal and neocortical neurons in emotionally negative
      situations in active and passive rabbits.
AB  - Cross-correlation histograms were used to compare the interaction of close-lying
      cells in the hippocampus (field CA1) and the parietal-temporal areas of the
      neocortex in active and passive rabbits during exposure to emotionally
      significant stimuli. Interaction of hippocampal neurons depended on the type of
      the behavioral response to the stimulus. The greatest changes from baseline were
      seen in active rabbits in orientational-investigative and active defensive
      reactions, while the greatest changes in passive animals were in freezing. In all
      states, cases of common inputs to hippocampal neurons were found more frequently
      in passive rabbits and excitatory links between neurons with short delays (up to
      40 msec) were more frequent in active rabbits. Interaction of neocortical
      neurons, in contrast with hippocampal neurons, was less dependent on the type of
      behavioral response to the stimulus and the animal's behavioral strategy. These
      results provide evidence of individual-typological features in information
      processing in hippocampal field CA1 in active and passive animals in emotionally
      negative situations.

PMID- 20146013
TI  - Segmentation, grouping and accentuation during stimulus perception.
AB  - Grouping, segmentation, and accentuation - processes involved in stimulus
      perception - are discussed. These effects are explained in terms of the universal
      vector coding model in neural networks. Grouping is the combination of objects or
      events into units on the basis of their similarity. Segmentation, conversely, is
      the separation of groups to the level of ensembles consisting of small numbers of
      objects. The processes of grouping and segmentation are regarded from the point
      of view of their underlying neural mechanisms. It is suggested that stimuli in
      neural networks are encoded by patterns of excitation of cardinal neurons. These
      excitation patterns can be represented as excitation vectors. Differences between
      stimuli are formed as the absolute magnitudes of their vector differences. The
      greater the perceived stimuli differ from each other, the greater the difference
      in their perceptual and semantic excitation vectors. The more similar the
      stimuli, the smaller their vector difference. This suggests that stimuli with
      similar excitation vectors will be grouped together in perceptual space.
      Conversely, stimuli with different excitation vectors will "repel" and become
      segmented. The spatial separation of objects increases with increases in the
      differences between their spatial excitation vectors. The universality of the
      vector coding principle can be illustrated using color contrast as an example:
      differences in contrasting colors increase with increases in the differences
      between their excitation vectors. Groups of objects with similar excitation
      vectors are accentuated in perception by means of summation of their excitation
      vectors. Groups of objects with different excitation vectors undergo mutual
      accentuation because of the appearance of contrast. Plastic accentuation is
      associated with the novelty of stimuli and is extinguished on repetition of the
      stimulus.

PMID- 20146014
TI  - Transfection of nerve cells.
AB  - Transfection is a method of transforming cells based on the introduction into
      living cells of plasmids encoding a particular protein or RNA. This review
      describes the main methods of transfection and considers their advantages and
      disadvantages. Most attention is paid to lentivirus transduction as one of the
      most efficient methods for transforming nerve cells. The development of current
      transfection systems based on lentivirus vectors is described and a brief review
      of studies performed using in vivo and in vitro lentivirus transfection of nerve
      cells is presented.

PMID- 20146015
TI  - Regulation of food consumption during pregnancy and lactation in mice.
AB  - The aim of the present work was to assess the expression of agouti-like protein
      and neuropeptide Y in pregnant and lactating mice and to compare this with the
      leptin level and food consumption. Food consumption, blood leptin levels, and
      agouti-like protein and neuropeptide Y mRNA levels in the hypothalamus of
      C57Bl/6J mice were assessed on days 7, 13, and 18 of pregnancy and on days 10 and
      21 of lactation, and in virgin females of the same ages. During pregnancy, food
      consumption and leptin levels decreased on day 7 and increased in day 18 of
      pregnancy, while neuropeptide Y mRNA levels increased on day 13 and then remained
      unaltered, and the agouti-like protein level increased on day 18. After
      parturition, food consumption continued to increase, while leptin levels and
      neuropeptide Y mRNA levels decreased to normal. Thus, hyperphagia in pregnancy
      was due to sequential activation of the expression of neuropeptide Y and agouti
      like protein, while in lactation hyperphagia resulted from mechanisms not
      associated with changes in the expression of these neuropeptides.

PMID- 20146016
TI  - Gender-related characteristics of responding to prolonged psychoemotional stress
      in mice.
AB  - The behavior of male and female C57BL/6J mice was studied after prolonged
      psychoemotional stress imposed by enforced cohabitation with an aggressive male
      on the other side of a partition in the cage and daily witnessing of 10-minute
      confrontations between the aggressor and another male placed with it. The
      elevated plus maze test demonstrated marked anxiety in mice of both genders after
      one month of psychoemotional stress. However, only females, but not males, showed
      an increase in the duration of passive swimming in the Porsolt test, along with
      some reduction in communicativeness in the partition test. Thus, these studies
      showed a more marked reaction to prolonged pscyhoemotional stress in females than
      in males.

PMID- 20146017
TI  - Age-related changes in rhythmic electrical activity in the cervical sympathetic
      trunk in rats and cats.
AB  - Baseline electrical activity in the cervical sympathetic trunk was studied in
      neonatal rats and cats and at ages 10, 20, and 30 days and two and six months,
      using spectral analysis. Rats from the neonatal period to the end of the first
      month of life and cats to 20 days of life showed increases at the amplitudes of
      electrical oscillations. From birth, all animals showed oscillations in the
      respiratory and cardiac rhythms. From day 20, frequencies with a cardiac
      component in rats dominated the power spectrum. The proportion of other
      frequencies, not associated with the cardiac or respiratory rhythms, was smaller.
      In cats, unlike the situation in rats, there were no age-related changes in the
      spectral composition of baseline electrical activity. High-frequency oscillations
      were recorded in cats from birth.

PMID- 20146018
TI  - Activity in the hypothalamo-hypophyseal-adrenocortical system on experimental
      induction of chronic fatigue syndrome.
AB  - Changes in the activity of the hypothalamo-hypophyseal-adrenocortical system
      (HHACS) were studied in an experimental model of chronic fatigue syndrome induced
      by i.p. administration of synthetic doublestranded RNA
      (polyriboinosinic:polyribocytidylic acid, Poly I:C) at a dose of 3 mg/kg.
      Functional changes in the different components of the HHACS were detected using
      standard tests with i.p. ACTH or hydrocortisone on the background of cold stress
      and injections of Poly I:C. Single doses of Poly I:C were followed by the
      development of impairments to HHACS function, with decreases in the ACTH
      sensitivity of adrenal cells and suppression of the negative feedback mechanism,
      resulting in significant decreases in corticosterone concentrations in standard
      tests with administration of ACTH and hydrocortisone.

PMID- 20146019
TI  - Convulsive activity in the electroencephalogram in rats sensitive and tolerant to
      pentylenetetrazol kindling.
AB  - Studies on rats divided into two groups with different sensitivities on the basis
      of manifest convulsive activity in response to pentylenetetrazol kindling showed
      that both "tolerant" and "sensitive" rats showed convulsive discharges on EEG
      traces. However, as compared with values in "tolerant" rats, the number of
      convulsive discharges in "sensitive" rats was 60% greater, convulsive discharges
      occurred 45 sec later, and had a duration in the first 45 post-injection minutes
      which was 70% longer. There was no difference between the mean durations of
      convulsive discharges in the two groups. The EEG frequency power peak in
      "tolerant" rats was more marked than that in "sensitive" animals, and was located
      at 7.2 Hz. These data led to the conclusion that pentylenetetrazol kindling
      induces epileptic activity on the EEG in rats independently of whether or not the
      animals showed behavioral seizures, though there were significant differences in
      measures of this activity in "sensitive" and "tolerant" rats.

PMID- 20146020
TI  - The influence of fluid flow on modeling quorum sensing in bacterial biofilms.
AB  - In this paper, we study quorum sensing in Pseudomonas aeruginosa biofilms. Quorum
      sensing is a process where bacteria monitor their population density through the
      release of extra-cellular signalling molecules. The presence of these molecules
      affects gene modulation leading to changes in behaviour such as the release of
      virulence factors. Here, we use numerical methods to approximate a 2-D model of
      quorum sensing. It is observed that the shape of the biofilm can have a profound
      effect on the onset of quorum sensing. This has serious repercussions for
      experimental observations since biofilms of the same biomass but different shapes
      can produce quite different results.

PMID- 20146021
TI  - Replicator equations and the principle of minimal production of information.
AB  - Many complex systems in mathematical biology and other areas can be described by
      the replicator equation. We show that solutions of a wide class of replicator
      equations minimize the KL-divergence of the initial and current distributions
      under time-dependent constraints, which in their turn, can be computed explicitly
      at every instant due to the system dynamics. Therefore, the Kullback principle of
      minimum discrimination information, as well as the maximum entropy principle, for
      systems governed by the replicator equations can be derived from the system
      dynamics rather than postulated. Applications to the Malthusian inhomogeneous
      models, global demography, and the Eigen quasispecies equation are given.

PMID- 20146022
TI  - Racial/ethnic discrimination in health care: impact on perceived quality of care.
AB  - BACKGROUND: Racial/ethnic minorities are more likely to report receipt of lower
      quality of health care; however, the mediators of such patient reports are not
      known. OBJECTIVES: To determine (1) whether racial disparities in perceptions of
      quality of health care are mediated by perceptions of being discriminated against
      while receiving medical care and (2) whether this association is further mediated
      by patient sociodemographic characteristics, access to care, and patient
      satisfaction across racial/ethnic groups. RESEARCH DESIGN: A cross-sectional
      analysis of a population-based sample of California adults responding to the 2003
      California Health Interview Survey. Multivariable logistic regression was used to
      examine the relationship between perceived discrimination and perceived quality
      of health care after adjusting for patient characteristics and reports of access
      to care. MAIN RESULTS: A total of 36,831 respondents were included. African
      Americans (68.7%) and Asian/Pacific Islanders (64.5%) were less likely than non
      Hispanic whites (72.8%) and Hispanics (74.9%) to rate their health care quality
      highly. African Americans (13.1%) and Hispanics (13.4%) were the most likely to
      report discrimination, followed by Asian/Pacific Islanders (7.3%) and non
      Hispanic whites (2.6%). Racial/ethnic discrimination in health care was
      negatively associated with ratings of health care quality within each
      racial/ethnic group, even after adjusting for sociodemographic variables and
      other indicators of access and satisfaction. Feeling discriminated against fully
      accounted for the difference in low ratings of quality care between African
      Americans and whites, but not for other racial/ethnic minorities. CONCLUSIONS:
      Patient perceptions of discrimination may play an important, yet variable role in
      ratings of health care quality across racial/ethnic minority groups. Health care
      institutions should consider how to address this patient concern as a part of
      routine quality improvement.

PMID- 20146023
TI  - Endoscopic treatment for Barrett's esophagus and early esophageal cancer.

PMID- 20146024
TI  - Inhibitory effect of galanin on adrenaline- and noradrenaline-induced increased
      oxytocin secretion in rat neurohypophyseal cell cultures.
AB  - The effects of the interactions between the 29 amino acid-containing peptide
      galanin and adrenaline or noradrenaline on the secretion of oxytocin were studied
      in 13- to 14-day cultures of isolated rat neurohypophyseal tissue. The alpha
      receptor antagonist corynanthine blocked the adrenaline-induced increase of
      oxytocin secretion. When the beta-receptor antagonist propranolol was added
      before the noradrenaline treatment, the antagonist prevented the noradrenaline
      induced enhancement of oxytocin release. Following the addition of galanin, the
      extent of oxytocin secretion into the supernatant medium decreased. Adrenaline
      and noradrenaline treatments increased the oxytocin level. Preincubation with
      galanin reduced the adrenaline- and noradrenaline-induced oxytocin level
      elevations. The blocking effect of galanin was prevented by previous treatment
      with the galanin receptor antagonist galantid (M15). When adrenaline or
      noradrenaline treatment was applied before galanin addition, the oxytocin
      secretion remained enhanced. The present results indicate that the changes in
      oxytocin secretion induced by the adrenergic system can be directly influenced by
      the galaninergic system. The interactions between the adrenergic and galaninergic
      systems from the aspect of oxytocin secretion can occur at the level of the
      posterior pituitary, independently of the hypothalamus.

PMID- 20146025
TI  - Infectious vasculopathy of intracranial large- and medium-sized vessels in
      neurological intensive care unit: a clinico-radiological study.
AB  - BACKGROUND: Infections are a well-known cause of cerebral vasculopathy and
      vasculitis. We aimed to analyze the frequency of intracranial vasculopathy
      attributable to infection, the spectrum of causative microorganisms, imaging, and
      cerebrospinal fluid (CSF) characteristics as well as clinical course and outcome.
      METHODS: We used our institution's medical record system to identify all patients
      diagnosed with nonatherosclerotic central nervous system vasculopathy from
      January 1, 1999 through February 28, 2009. We reviewed their clinical charts,
      imaging data, and results of CSF studies. RESULTS: Twenty-five adult patients
      with nonatherosclerotic cerebral vasculopathy of large- and medium-sized
      intracranial vessels were identified. Eight patients had vasculopathy
      attributable to infection (32%). The underlying pathologies were acute bacterial
      meningitis (n = 4), varicella zoster virus (VZV) infection (n = 2), borreliosis
      (n = 1), and syphilis (n = 1). In six patients, magnetic resonance angiography
      was performed and showed vasculopathic changes in all patients examined (100%).
      In both patients with VZV-associated vasculopathy, the arterial wall enhanced on
      magnetic resonance imaging. The CSF examination of the patients with infectious
      vasculopathy showed a significantly higher white blood cell count. The outcome of
      the infectious cohort was unfavorable with one death, two patients with locked-in
      syndrome, and five patients discharged from intensive care with severe
      neurological deficits. CONCLUSION: In this cohort, one-third of all cases of
      nonatherosclerotic vasculopathy were due to infectious vasculopathy of large and
      medium intracranial vessels.

PMID- 20146026
TI  - How I cool children in neurocritical care.
AB  - Brain injury is the leading cause of death in our pediatric ICU [Au et al. Crit
      Care Med 36:A128, 2008]. Clinical care for brain injury remains largely
      supportive. Therapeutic hypothermia has been shown to be effective in improving
      neurological outcome after adult ventricular-arrhythmia-induced cardiac arrest
      and neonatal asphyxia, and is under investigation as a neuroprotectant after
      cardiac arrest and traumatic brain injury in children in our ICU and other
      centers. To induce hypothermia in children comatose after cardiac arrest we
      target 32-34 degrees C using cooling blankets and intravenous iced saline as
      primary methods for induction, for 24-72 h duration with vigilant re-warming. The
      objective of this article is to share our hypothermia protocol for cooling
      children with acute brain injury.

PMID- 20146027
TI  - Incrementally applied multifaceted therapeutic bundles in neuroprotection
      clinical trials...time for change.

PMID- 20146028
TI  - Outcome of allogeneic bone marrow transplantation from unrelated donors for adult
      Philadelphia chromosome-negative acute lymphocytic leukemia in first complete
      remission.
AB  - The indication of allogeneic stem cell transplantation (allo-SCT) for
      Philadelphia chromosome-negative acute lymphocytic leukemia [Ph(-) ALL] from
      unrelated donors is not established. To assess its potency of unrelated patients
      in first complete-remission (CR1) transplanted from unrelated donors and the
      potential prognostic factors affecting the probability of survival, we
      retrospectively analyzed a total of 41 adult Ph(-) ALL patients in CR1 who
      underwent unrelated bone marrow transplantation at 6 transplantation centers of
      the Nagoya Blood and Marrow Transplantation Group between 1993 and 2006. The
      median age of the 41 patients was 28 years (range, 18-51 years). HLA was matched
      in 33 transplants, with mismatches in 8 (HLA-A allele mismatch:1, HLA-DR
      serological mismatch: 2, HLA-DRB1 mismatch: 5). Leukemia-free survival (LFS) at 3
      and 6 years from allo-SCT was 60.3 and 47.7%, respectively. LFS at 5 years was
      62.1% for those transplanted from HLA-matched donors. LFS was significantly lower
      with HLA-mismatched donors due to higher transplantation-related mortality.
      Relapse was observed in 3 patients. Our study suggested that unrelated allo-SCT
      could improve LFS of patients with a potential graft-versus-leukemia effect.
      Unrelated allo-SCT for Ph(-) ALL patients in CR1 could be more beneficial by
      reducing TRM, such as selecting a HLA-matched donor.

PMID- 20146030
TI  - Pediatric myeloid/NK cell precursor lymphoma/leukemia expressing T/NK
      immunophenotype markers.
AB  - Myeloid/NK cell precursor lymphoma/leukemia has been suggested to be of precursor
      NK origin. We report a 1-year-old boy with myeloid/NK cell precursor
      lymphoma/leukemia who presented with a skin nodule. Biopsy of the skin nodule
      specimen revealed CD45(+), CD56(+), myeloid antigen(+), CD7(-), CD3(-), CD19(-),
      CD34(-), CD4(-) by flow cytometry and myeloperoxidase (MPO)(+), TdT(+),
      cytoplasmic CD3(+) by immunohistochemistry. He received acute myeloid leukemia
      oriented combination chemotherapy. Although his skin nodule disappeared, regrowth
      was observed; a biopsy was performed again, showing that the immunophenotype was
      CD56(+), myeloid antigen(+), HLA-DR(+), MPO(-), CD3(+) and TCRgammadelta(+).
      Being refractory to chemotherapy, he underwent stem cell transplantation from his
      father. However, he relapsed again and died from septic shock. Although
      myeloid/NK cell precursor acute leukemia is characterized by CD7(+), CD56(+),
      CD3(-), CD34(+) and myeloid antigen(+) phenotype, the blast cells of our patients
      lacked CD34 and CD7 expression while expressing myeloid antigens. Furthermore,
      CD94 1A transcripts were predominantly expressed rather than CD94 1B, implying
      their origin in immature NK cells. After acute myeloid leukemia-oriented
      combination chemotherapy, his blasts acquired stable CD3 expression and
      TCRgammadelta rearrangement at recurrence. The blast cells possessed features
      overlapping both myeloid/NK precursor acute leukemia and blastic NK/precursor
      acute lymphoma/leukemia. These observations suggest that two subclones originated
      from common precursors.

PMID- 20146029
TI  - Guidelines for safety management of granulocyte transfusion in Japan.
AB  - Granulocyte transfusion (GTX) has recently been revived by the ability to
      stimulate granulocyte donors with granulocyte colony-stimulating factor (G-CSF),
      resulting in a greatly increased number of cells that can be collected. However,
      there is a paucity of guidelines for assessing the appropriateness and safety
      management of GTX. The objective of this study was to establish guidelines for
      the safety management of GTX appropriate for the clinical situation in Japan. The
      Japan Society of Transfusion Medicine and Cell Therapy, Granulocyte Transfusion
      Task Force issued the first version of guidelines for GTX considering the safety
      management of both granulocyte donors and patients who receive GTX therapy. The
      current guidelines cover issues concerning: (1) the appropriateness of medical
      institutions, (2) management of granulocyte donors, (3) quality assurance of
      granulocyte concentrates, (4) administration of granulocyte concentrates, (5)
      evaluation of the effectiveness of GTX therapy, and (6) complications of GTX
      therapy. The simple 'bag separation method' without apheresis may be recommended
      for granulocyte collection in pediatric patients. The first version of guidelines
      for GTX therapy has been established, which may be appropriate for the clinical
      situation in Japan. Care should be taken to perform the safety management of both
      granulocyte donors and patients who receive GTX therapy.

PMID- 20146031
TI  - Emergence of chronic myelogenous leukemia during treatment for essential
      thrombocythemia.
AB  - A 72-year-old male patient was initially diagnosed with essential thrombocythemia
      (ET), a Philadelphia chromosome-negative (Ph1(-)) chronic myeloproliferative
      disorder (CMPD), and was treated with hydroxyurea (HU). After 9 years of
      diagnosis of ET, his peripheral leukocytes gradually increased, while his
      platelet count showed a decrease. Bone marrow analysis disclosed Ph-positive
      chronic myelogenous leukemia (CML) in the chronic phase. Administration of
      imatinib mesylate (IM), a Bcr-Abl tyrosine kinase inhibitor (TKI), induced
      complete hematologic response in a month, but was discontinued after 4 months
      because of Grade 3 pleural effusion (PE). The treatment was switched to nilotinib
      which successfully induced a complete cytogenetic response (CCyR) after 5 months
      of TKI therapy and resolved the PE. Despite CCyR, however, ET recurred. Since
      then, the patient has been treated for 8 months with a combination of nilotinib
      and HU which has successfully controlled both CML and ET. This report includes a
      review of the characteristics of 15 reported cases with co-occurrence of CML and
      Bcr-Abl-negative CMPDs, including ours. Although rare, care needs to be taken
      since, despite the often similar clinical features of the two diseases, they
      require completely different treatments.

PMID- 20146033
TI  - Development of Kaposi's sarcoma after complete remission of multicentric
      Castlemans disease with rituximab therapy in a HHV8-positive, HIV-negative
      patient.

PMID- 20146034
TI  - Intercalary allograft reconstructions using a compressible intramedullary nail: a
      preliminary report.
AB  - BACKGROUND: Although intercalary allograft reconstructions are commonly performed
      using intramedullary devices, they cannot generate compression across host
      allograft junctions. Therefore, they sometimes are associated with gap formation
      and suboptimal healing conditions. QUESTIONS/PURPOSES: We describe a new
      technique and present preliminary results for intercalary allograft
      reconstructions for tumors using a compressible intramedullary nail. PATIENTS AND
      METHODS: We retrospectively reviewed 10 patients (19 host-allograft junctions)
      who underwent intercalary allograft reconstruction using the compression nailing
      technique. Two patients were excluded as they had additional vascularized fibular
      autografts, leaving 15 junctions in eight patients for analysis. Three of the
      intercalary reconstructions had supplemental plate fixation at one junction. All
      patients received host bone reamings and cancellous allograft and one had bone
      marrow aspirate and demineralized bone matrix in addition to the cancellous
      allograft. The minimum followup was 3 months (mean, 18 months; range, 3-39
      months). RESULTS: Thirteen of 15 junctions healed without additional surgery. Two
      diaphyseal-diaphyseal junctions did not unite after allograft arthrodeses. One
      patient underwent revision for nonunion 8 months after the initial procedure,
      with subsequent healing. The second patient had no evidence of union at 6 months,
      after which he was lost to followup. There were no allograft fractures or
      infections in any reconstruction. One patient died of metastatic renal cell
      carcinoma, and one patient had multicentric local soft tissue recurrences of a
      periosteal osteosarcoma requiring resection. CONCLUSIONS: Our early observations
      indicate newer compressible intramedullary nails reliably address junctional gap
      formation, providing for a high rate of union while retaining the long-term
      benefits of intramedullary stabilization. LEVEL OF EVIDENCE: Level IV, case
      series. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 20146035
TI  - Case report: Osteonecrosis of the femoral head after hip arthroscopy.
AB  - BACKGROUND: Hip arthroscopy is a common orthopaedic procedure used as a
      diagnostic and therapeutic tool with a multitude of surgical indications. The
      complication rate is reportedly between 1.3% and 23.3%. Major complications are
      related to traction, fluid extravasation, and iatrogenic chondral injury.
      Although osteonecrosis is a concern with any surgical procedure about the hip,
      this complication has been primarily a theoretical concern with hip arthroscopy.
      CASE DESCRIPTION: We report the case of a 24-year-old man who presented with a 2
      year history of left hip pain. He underwent hip arthroscopy to include
      debridement of a torn labrum and removal of a prominent pincer lesion for
      femoroacetabular impingement. Traction was initiated by applying manual traction
      to the traction bar until 10 mm of joint distraction was obtained. Traction was
      removed at 90 minutes. At the 3-month followup, MRI showed osteonecrosis in the
      subcapital region of the left femoral head. LITERATURE REVIEW: It generally is
      agreed the magnitude and duration of traction during hip arthroscopy increase the
      risk of traction-related injuries. Only one previous case of femoral head
      osteonecrosis associated with hip arthroscopy has been reported, and this may
      have resulted from the initial traumatic event. Based on anatomic studies, the
      use of standard arthroscopic portals would not put at risk any dominant normal
      vascular structures supplying the femoral head. In contrast, the literature shows
      that femoral head osteonecrosis may develop secondary to a combination of
      increased intraarticular pressure and traction. PURPOSES AND CLINICAL RELEVANCE:
      We suspect this case of femoral head osteonecrosis after hip arthroscopy was
      caused by traction used in the procedure.

PMID- 20146036
TI  - In brief: meniscal tears.

PMID- 20146037
TI  - The classic: on the theory of fracture healing. 1873.

PMID- 20146038
TI  - Positive psychology in cancer care: bad science, exaggerated claims, and unproven
      medicine.
AB  - BACKGROUND: Claims of positive psychology about people with cancer enjoy great
      popularity because they seem to offer scientific confirmation of strongly held
      cultural beliefs and values. PURPOSE: Our goal is to examine critically four
      widely accepted claims in the positive psychology literature regarding
      adaptational outcomes among individuals living with cancer. METHODS: We examine:
      (1) the role of positive factors, such as a "fighting spirit" in extending the
      life of persons with cancer; (2) effects of interventions cultivating positive
      psychological states on immune functioning and cancer progression and mortality;
      and evidence concerning (3) benefit finding and (4) post-traumatic growth
      following serious illness such as cancer and other highly threatening
      experiences. RESULTS: Claims about these areas of research routinely made in the
      positive psychology literature do not fit with available evidence. We note in
      particular the incoherence of claims about the adaptational value of benefit
      finding and post-traumatic growth among cancer patients, and the implausibility
      of claims that interventions that enhance benefit finding improve the prognosis
      of cancer patients by strengthening the immune system. CONCLUSION: We urge
      positive psychologists to rededicate themselves to a positive psychology based on
      scientific evidence rather than wishful thinking.

PMID- 20146039
TI  - Cerebellar nuclei: key roles for strategically located structures.

PMID- 20146040
TI  - A two-center study of Muslim women's views of breast cancer and breast health
      practices in Pakistan and the UK.
AB  - Breast health awareness practices of Pakistani Muslim women in the UK and
      Pakistan is unknown. Focus group interviews were used to investigate the impact
      of culture and psychosocial issues on breast health awareness involving 44 women
      in Lahore and London. Women based in Lahore were more inquisitive about breast
      cancer and held more developed views compared with British Pakistani Muslim
      women. Women concurred that concise and relevant breast health education is
      needed irrespective of faith to improve cultural sensitivity and awareness in
      both Pakistani communities (both men and women).

PMID- 20146041
TI  - Evaluation of Cancer 101: an educational program for native settings.
AB  - This community-based intervention study examines the impact of Cancer 101, a
      cancer education resource developed in collaboration with American Indians/Alaska
      Natives to improve cancer knowledge, action regarding cancer control in tribal
      settings, and survival rates for members of their communities. Pre/post-surveys
      used to assess knowledge, attitudes, perceived benefits and future activities at
      baseline, immediately post-training, and at 4-6 months. Participants demonstrated
      significant change in knowledge, attitude, and cancer control activities. Cancer
      101 provides a critical pathway to increase knowledge and promote action to
      reduce the burden and improve survival of cancer within tribal communities.

PMID- 20146042
TI  - Evaluation of the breast cancer train the trainer program for nurses in Turkey.
AB  - The Breast Cancer Train the Trainer (TTT) program was designed to increase breast
      cancer awareness, improve knowledge about breast cancer among nurses, and provide
      quality care for breast cancer patients by trained nurses. A total of three
      programs were held and 82 nurses from different regions of Turkey attended this
      training. The educational activities employed several teaching and learning
      strategies. After completion, we determined that the participating nurses'
      knowledge on breast cancer had increased significantly, and they were satisfied
      with the training received. The Breast Cancer TTT program is a unique educational
      endeavor for nurses in Turkey, and our results showed that the training achieved
      its goal. Trained nurses in Breast Cancer TTT programs can help educate women
      about the importance of breast health and the measures they need to take to
      protect themselves against breast cancer. At the same time, nurses can also
      increase and enhance the quality of life in patients with breast cancer. This is
      an example of a program that can easily be spread throughout the world as it was
      done from England and Australia to Turkey.

PMID- 20146043
TI  - Adapting a program to inform African American and Hispanic American women about
      cancer clinical trials.
AB  - The dearth of evidence-based clinical trial education programs may contribute to
      the under-representation of African American and Hispanic American women in
      cancer research studies. This study used focus group-derived data from 80 women
      distributed among eight Spanish- and English-language focus groups. These data
      guided the researchers' adaptation and refinement of the National Cancer
      Institute's various clinical trials education programs into a program that was
      specifically focused on meeting the information needs of minority women and
      addressing the barriers to study participation that they perceived. A
      "sisterhood" theme was adopted and woven throughout the presentation.

PMID- 20146044
TI  - Barbers against prostate cancer: a feasibility study for training barbers to
      deliver prostate cancer education in an urban African American community.
AB  - The goal of this pilot study was to assess the feasibility of training barbers to
      deliver a brief culturally and literacy appropriate prostate cancer educational
      intervention to urban African American men. Eight barbers received training to
      deliver a 2-month educational intervention in the barbershop and completed pre-
      and posttest training assessments. The training workshops led to a significant
      increase in mean prostate cancer knowledge scores among the barbers (60% before
      vs. 79% after; P < 0.05). The barbers also reported positively on the
      intervention in terms of satisfaction and relative ease of engaging clients.
      Training barbers to deliver a prostate cancer educational intervention is a
      feasible strategy for raising prostate cancer awareness of the disease among a
      priority population.

PMID- 20146045
TI  - [Drug-induced osteopathies. Drugs, pathogenesis, forms, diagnosis, prevention and
      therapy].
AB  - A number of drugs can have "side effects" on bone metabolism and formation,
      causing bone atrophy, impaired mineralisation, as well as osteonecrosis. In both
      clinical and general practitioner settings, these forms of bone damage have been
      hitherto considered as adverse drug side effects and have received insufficient
      attention; moreover, they have not been the subject of patient information.
      Preventive measures are not instigated prior to initiation of medication and even
      after onset of bone damage, therapeutic strategies are poorly implemented. Even
      fracture healing with its complex, staged course can be both positively and
      negatively influenced by a number of drugs and these effects require monitoring.
      Recommendations regarding practical screening and therapy of drug-induced
      osteopathies are presented.

PMID- 20146048
TI  - [Gastrointestinal tumors : New N classification of the UICC].
AB  - Removal and examination of regional lymph nodes play an important role in the
      surgical therapy of gastrointestinal tumors concerning potential adjuvant
      treatment strategies. The number of metastatic regional lymph nodes as well as
      the number of removed and examined lymph nodes are of importance regarding
      estimation of the prognosis. It is essential to consider which lymph nodes are
      defined as regional in the UICC TNM classification and which definitions apply
      for the individual N categories. Furthermore, it is necessary to define which
      recommendations are valid for the minimum numbers of lymph nodes to be removed
      and examined for particular tumor entities.

PMID- 20146049
TI  - [Tumors of the lower gastrointestinal tract : Indication and extent of lymph node
      dissection].
AB  - Lymph node dissection is almost always indicated in the treatment of advanced
      colorectal carcinoma with curative intent. Investigation of at least 12 regional
      lymph nodes is required for adequate staging. The extent and quality of lymph
      node dissection influence the long-term prognosis, especially locoregional
      recurrences and long-term survival. The extent of lymphadenectomy depends on the
      tumour site and the pattern of potential lymphatic spread following the course of
      the blood vessels supplying the tumour. Important principles are central ligation
      of the supplying arteries and draining veins right at their roots, preservation
      of autonomous nerves at the trunk of the superior mesenteric artery and the aorta
      and preservation of the integrity of the mesocolon or mesorectum. The number of
      regional lymph nodes examined as well as the number of lymph nodes with
      metastases influence the prognosis. Systematic lymph node dissection is also
      recommended for carcinomas of the small bowel and in most neuroendocrine tumours
      or carcinomas but is not required for gastro-intestinal stromal tumours.

PMID- 20146050
TI  - [Patient clarification/pre-operative clarification].
AB  - Every medical intervention constitutes a physical injury and therefore requires
      the consent of the patient to avoid liability. In order that the patient can
      effectively consent to the intervention by ensuring autonomy of decision, the
      patient must be fully informed of the risks involved in medical interventions.
      The patient must be informed of the essential benchmark data however, it must be
      borne in mind that each individual case is always decisive for deciding whether
      clarification has been correctly carried out. In these instances individual
      factors, such as the personal background of the patient, play a role.
      Documentation of the clarification serves as proof that it has been carried out
      and to what extent.

PMID- 20146051
TI  - Skin and soft tissue infections in hospitalised patients with diabetes: culture
      isolates and risk factors associated with mortality, length of stay and cost.
AB  - AIMS/HYPOTHESIS: Skin and soft tissue infections (SSTIs) cause substantial
      morbidity in persons with diabetes. There are few data on pathogens or risk
      factors associated with important outcomes in diabetic patients hospitalised with
      SSTIs. METHODS: Using a clinical research database from CareFusion, we identified
      3,030 hospitalised diabetic patients with positive culture isolates and a
      diagnosis of SSTI in 97 US hospitals between 2003 and 2007. We classified the
      culture isolates and analysed their association with the anatomic location of
      infection, mortality, length of stay and hospital costs. RESULTS: The only
      culture isolate with a significantly increased prevalence was methicillin
      resistant Staphylococcus aureus (MRSA); prevalence for infection of the foot was
      increased from 11.6 to 21.9% (p < 0.0001) and for non-foot locations from 14.0%
      to 24.6% (p = 0.006). Patients with non-foot (vs foot) infections were more
      severely ill at presentation and had higher mortality rates (2.2% vs 1.0%, p <
      0.05). Significant independent risk factors associated with higher mortality
      rates included having a polymicrobial culture with Pseudomonas aeruginosa (OR
      3.1), a monomicrobial culture with other gram-negatives (OR 8.9), greater illness
      severity (OR 1.9) and being transferred from another hospital (OR 5.1). These
      factors and need for major surgery were also independently associated with longer
      length of stay and higher costs. CONCLUSIONS/INTERPRETATION: Among diabetic
      patients hospitalised with SSTI from 2003 to 2007, only MRSA increased in
      prevalence. Patients with non-foot (vs foot) infections were more severely ill.
      Independent risk factors for increased mortality rates, length of stay and costs
      included more severe illness, transfer from another hospital and wound cultures
      with Pseudomonas or other gram-negatives.

PMID- 20146052
TI  - Assessing prediction of diabetes in older adults using different adiposity
      measures: a 7 year prospective study in 6,923 older men and women.
AB  - AIMS/HYPOTHESIS: The aim of this study was to examine whether waist circumference
      (WC) or WHR improve diabetes prediction beyond body mass index in older men and
      women, and to define optimal cut-off points. METHODS: In this prospective study,
      non-diabetic men (n = 3,519) and women (n = 3,404) aged 60-79 years were followed
      up for 7 years. There were 169 and 128 incident cases of type 2 diabetes in men
      and women, respectively. RESULTS: BMI, WC and WHR all showed strong associations
      with incident type 2 diabetes independent of potential confounders. In men, the
      adjusted relative risks (top vs lowest quartile) were 4.71 (95% CI 2.45-9.03) for
      BMI, 3.53 (95% CI 1.92-6.48) for WC and 2.76 (95% CI 1.58-4.82) for WHR. For
      women, the corresponding relative risks were 4.10 (95% CI 2.16-7.79), 12.18 (95%
      CI 4.83-30.74) and 5.61 (95% CI 2.84-11.09) for BMI, WC and WHR, respectively.
      Receiver-operating characteristic curve analysis revealed similar associations
      for BMI and WC in predicting diabetes in men (AUC = 0.726 and 0.713,
      respectively); WHR was the weakest predictor (AUC = 0.656). In women, WC was a
      significantly stronger predictor (AUC = 0.780) than either BMI (AUC = 0.733) or
      WHR (AUC = 0.728; p < 0.01 for both). Inclusion of both WC and BMI did not
      improve prediction beyond BMI alone in men or WC alone in women. Optimal
      sensitivity and specificity for the prediction of type 2 diabetes was observed at
      a WC of 100 cm in men and 92 cm in women. CONCLUSIONS/INTERPRETATION: In older
      men, BMI and WC yielded similar prediction of risk of type 2 diabetes, whereas WC
      was clearly a superior predictor in older women.

PMID- 20146053
TI  - Suppression of lysyl oxidase gene expression by methylation in pelvic organ
      prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: We measured promoter methylation in the LOX gene in
      women with pelvic organ prolapse and in women without prolapse. METHODS: Genomic
      DNA was isolated from the uterosacral ligaments of eight women with prolapse and
      eight women without prolapse as controls. Genomic DNA was digested with BamHI and
      underwent sodium bisulfite modification. The LOX gene promoter region of -246 to
      +74 was then amplified by PCR, cloned into PCR2.1-TOPO and transformed into an
      Escherichia coli DH5alpha strain. Amplified plasmid DNA samples containing the
      LOX gene promoter region from each woman were sequenced and methylated CpG
      islands were identified by sequence comparison. RESULTS: A total of 66 methylated
      CpG sites were found in the group of patients with prolapse, while only one
      methylated CpG site was found in the non-prolapse control group. CONCLUSIONS:
      Methylation in the promoter region may suppress LOX gene expression in women with
      pelvic organ prolapse.

PMID- 20146054
TI  - Retrospective case modelling to assess the impact of early intervention for
      voiding dysfunction after retropubic tape. When is it best to intervene?
AB  - INTRODUCTION AND HYPOTHESIS: This study is a retrospective modelling of early
      intervention for voiding difficulties (VD) after retropubic tape insertion.
      METHODS: Chart review assessing Trial Without Catheter (TWOC) on day 2 and day 9
      and long-term VD. Number needed to treat (NNT) analysis performed for presumed
      intervention on days 2 and 9. RESULTS: Thirty seven (22%) of 171 patients failed
      TWOC on day 2, 20 (12%) on day 9. Ten (6%) had VD at 6 months. Five elected to
      have the tape cut. One had recurrence of SUI. NNT was 7.4:1 on day 2 and 4:1 on
      day 9 to avoid per tapes being cut at 6 months. Early intervention would
      potentially lead to six and three additional failures, respectively, assuming 80%
      continence. This represents over 100 per annum in the United Kingdom.
      CONCLUSIONS: The majority of VD after retropubic tape insertion will resolve.
      Early intervention may lead to additional failures.

PMID- 20146055
TI  - Midline fascial plication under continuous digital transrectal control: which
      factors determine anatomic outcome?
AB  - INTRODUCTION AND HYPOTHESIS: The aim of the study was to report anatomic and
      functional outcome of midline fascial plication under continuous digital
      transrectal control and to identify predictors of anatomic failure. METHODS:
      Prospective observational cohort. Anatomic success defined as POP-Q stage <or= I
      of the posterior compartment. Validated questionnaires to measure bother and
      impact on quality of life. Logistic regression to identify risk factors for
      anatomic failure. RESULTS: Two hundred thirty-three patients with posterior
      pelvic organ prolapse (POP) stage >or= II underwent midline fascial plication
      under continuous digital transrectal control. Median follow-up was 14 months (12
      35 months), and anatomic success was 80.3% (95% CI 75-86). Independent predictors
      of failure were posterior compartment POP stage >or= III [OR 8.7 (95% CI 2.7
      28.1)] and prior colposuspension [OR 5.6 (95% CI 1.1-27.8)]. Sixty-three percent
      of patients bothered by obstructed defaecation experienced relief after surgery.
      CONCLUSIONS: Anatomic and functional outcomes were good. Risk factors for
      anatomic failure were initial size of posterior POP (stage >or= III) and prior
      colposuspension.

PMID- 20146056
TI  - Reliability and clinical validity of a Polish version of the CONTILIFE: a quality
      of life questionnaire for urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The primary aim of the study was to translate and
      validate a Polish version of the CONTILIFE, a quality of life questionnaire. The
      clinical validity of the CONTILIFE was assessed against the number of urinary
      leaks, Valsalva leak point pressure (VLPP), and maximum urethral closure pressure
      (MUCP). METHODS: One hundred women with stress urinary incontinence completed a
      Polish version of the CONTILIFE twice with a 4-day interval. RESULTS: Internal
      consistency (Cronbach's alpha= 0.94) and test-retest reliability of the
      instrument (ICC = 0.96) were very good. A significant relationship was found
      between all the CONTILIFE dimension scores, the CONTILIFE global score, and the
      number of urinary leaks per week. A less significant relationship was found
      between VLPP, MUCP, and CONTILIFE dimension and global scores. CONCLUSIONS: A
      Polish version of the CONTILIFE can be a reliable measure of quality of life in
      stress urinary incontinence patients.

PMID- 20146057
TI  - The "flipped" state in E71A-K+-channel KcsA exclusively alters the channel gating
      properties by tetraethylammonium and phosphatidylglycerol.
AB  - Mutation E71A in the bacterial K(+)-channel KcsA has been shown to abolish the
      activation-coupled inactivation of KcsA via significant alterations of the
      peptide backbone in the vicinity of the selectivity filter. In the present study,
      we examined channel-blocking behavior of KcsA-E71A by tetraethylammonium (TEA)
      from both the extra- and the intracellular sides. First, we found that E71A is
      inserted either in cis or trans orientation in a planar lipid bilayer; however,
      it exhibits only one orientation in proteoliposomes as determined by
      extravesicular partial chymotrypsin digestion. Second, E71A exhibits a lower
      extracellular TEA affinity and is more sensitive to intracellular TEA compared to
      wild-type KcsA, which apparently has >50-fold higher affinity for extracellular
      TEA and approximately 2.5-fold lower affinity for intracellular TEA compared to
      E71A. In additional experiments, we investigated the influence of negatively
      charged phosphatidylglycerol (PG) on channel-gating properties in
      phosphatidylcholine lipid bilayers. It was found that high PG content decreases
      the single-channel conductance and increases the channel open time and open
      probability. Taken together, our data suggest that the "flipped" conformation of
      the selectivity filter present in E71A allows weaker extracellular and stronger
      intracellular TEA binding, whereas higher PG content decreases channel
      conductivity and stabilizes the channel open "flipped" state via electrostatic
      interaction in the proximity of the channel pore.

PMID- 20146058
TI  - Influence of the use of statin on the stability of erythrocyte membranes in
      multiple sclerosis.
AB  - Multiple sclerosis (MS) probably occurs by oxidative, inflammatory and autoimmune
      mechanisms. This study investigated the influence of statin on the stability of
      erythrocyte membranes in MS patients. The population was composed of one group
      with simvastatin therapy (20 mg/day), another group without statin therapy and a
      healthy control group. The stability of erythrocytes was evaluated by the half
      transition points, H(50) and D(50), obtained from the curves of hemolysis induced
      by hypotonic shock and ethanol action, respectively. Erythrocytes of MS patients
      were less stable against lysis by both chaotropes. This behavior may be merely a
      consequence of the lifestyle of MS patients or it may be intrinsically associated
      with the conjunct of factors responsible for the development of the disease. The
      use of statin by MS patients was associated with lower levels of LDL and total
      cholesterol, as expected, and with higher stability of erythrocytes against
      ethanol compared to the values of untreated MS patients.

PMID- 20146060
TI  - Nitrification and degradation of halogenated hydrocarbons--a tenuous balance for
      ammonia-oxidizing bacteria.
AB  - The process of nitrification has the potential for the in situ bioremediation of
      halogenated compounds provided a number of challenges can be overcome. In
      nitrification, the microbial process where ammonia is oxidized to nitrate,
      ammonia-oxidizing bacteria (AOB) are key players and are capable of carrying out
      the biodegradation of recalcitrant halogenated compounds. Through industrial
      uses, halogenated compounds often find their way into wastewater, contaminating
      the environment and bodies of water that supply drinking water. In the
      reclamation of wastewater, halogenated compounds can be degraded by AOB but can
      also be detrimental to the process of nitrification. This minireview considers
      the ability of AOB to carry out cometabolism of halogenated compounds and the
      consequent inhibition of nitrification. Possible cometabolism monitoring methods
      that were derived from current information about AOB genomes are also discussed.
      AOB expression microarrays have detected mRNA of genes that are expressed at
      higher levels during stress and are deemed "sentinel" genes. Promoters of
      selected "sentinel" genes have been cloned and used to drive the expression of
      gene-reporter constructs. The latter are being tested as early warning biosensors
      of cometabolism-induced damage in Nitrosomonas europaea with promising results.
      These and other biosensors may help to preserve the tenuous balance that exists
      when nitrification occurs in waste streams containing alternative AOB substrates
      such as halogenated hydrocarbons.

PMID- 20146059
TI  - The evolution of fatty acid desaturases and cytochrome b5 in eukaryotes.
AB  - Desaturases that introduce double bonds into the fatty acids are involved in the
      adaptation of membrane fluidity to changes in the environment. Besides,
      polyunsaturated fatty acids (PUFAs) are increasingly recognized as important
      pharmaceutical and nutraceutical compounds. To successfully engineer organisms
      with increased stress tolerance or the ability to synthesize valuable PUFAs,
      detailed knowledge about the complexity of the desaturase family as well as
      understanding of the coevolution of desaturases and their cytochrome b5 electron
      donors is needed. We have constructed phylogenies of several hundred desaturase
      sequences from animals, plants, fungi and bacteria and of the cytochrome b5
      domains that are fused to some of these enzymes. The analysis demonstrates the
      existence of three major desaturase acyl-CoA groups that share few similarities.
      Our results indicate that the fusion of Delta(6)-desaturase-like enzymes with
      their cytochrome b5 electron donor was a single event that took place in the
      common ancestor of all eukaryotes. We also propose the Delta(6)-desaturase-like
      enzymes as the most probable donor of the cytochrome b5 domain found in fungal
      Delta(9)-desaturases and argue that the recombination most likely happened soon
      after the separation of the animal and fungal ancestors. These findings answer
      some of the previously unresolved questions and contribute to the quickly
      expanding field of research on desaturases.

PMID- 20146061
TI  - The role of salicylate and biosurfactant in inducing phenanthrene degradation in
      batch soil slurries.
AB  - The majority of polycyclic aromatic hydrocarbons (PAHs) sorb strongly to soil
      organic matter posing a complex barrier to biodegradation. Biosurfactants can
      increase soil-sorbed PAHs desorption, solubilisation, and dissolution into the
      aqueous phase, which increases the bioavailability of PAHs for microbial
      metabolism. In this study, biosurfactants, carbon sources, and metabolic pathway
      inducers were tested as stimulators of microorganism degradation. Phenanthrene
      served as a model PAH and Pseudomonas putida ATCC 17484 was used as the
      phenanthrene degrading microorganism for the liquid solutions and soil used in
      this investigation. Bench-scale trials demonstrated that the addition of
      rhamnolipid biosurfactant increases the apparent aqueous solubility of
      phenanthrene, and overall degradation by at least 20% when combined with
      salicylate or glucose in liquid solution, when compared to solutions that
      contained salicylate or glucose with no biosurfactant. However, salicylate
      addition, with no biosurfactant addition, increased the total degradation of
      phenanthrene 30% more than liquid systems with only biosurfactant addition. In
      soil slurries, small amounts of biosurfactant (0.25 g/L) showed a significant
      increase in total removal when only biosurfactant was added. In soil slurries
      containing salicylate, the effects of biosurfactant additions were negligible as
      there was greater than 90% removal, regardless of the biosurfactant
      concentration. The results of experiments performed in this study provide further
      evidence that an in situ enhancement strategy for phenanthrene degradation could
      focus on providing additional carbon substrates to induce metabolic pathway
      catabolic enzyme production, if degradation pathway intermediates are known.

PMID- 20146062
TI  - Microbial L-methioninase: production, molecular characterization, and therapeutic
      applications.
AB  - L-methioninase is ubiquitous in all organisms except in mammals. It mainly
      catalyzes the, alpha, gamma-elimination of L: -methionine to alpha-ketobutyrate,
      methanethiol, and ammonia. Unlike normal cells, methionine dependency was
      reported as a biochemical phenomenon among various types of cancer cells. Thus, L
      methioninase is the universal protocol for triggering the majority of tumor
      cells. This review is an attempt to briefly describe the occurrence of the
      biochemical and molecular properties of L-methioninase by a comparative manner to
      the eukaryotic and prokaryotic source for the maximum exploitation in the
      therapeutic field. The combination of L-methioninase treatment, gene therapy, and
      chemotherapeutic drugs clearly explores the various therapeutic aspects of this
      enzyme. Finally, the perspectives for increasing the therapeutic efficacy of this
      enzyme were described.

PMID- 20146063
TI  - A randomized phase II trial of personalized peptide vaccine plus low dose
      estramustine phosphate (EMP) versus standard dose EMP in patients with castration
      resistant prostate cancer.
AB  - Personalized peptide vaccination (PPV) combined with chemotherapy could be a
      novel approach for many cancer patients. In this randomized study, we evaluated
      the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate
      (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with
      castration resistant prostate cancer. Patients were randomized into groups
      receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560
      mg/day). After disease progression, patients were switched to the opposite
      regime. The primary end point was progression-free survival (PFS). We randomly
      assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive
      standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP
      group occurred during the first treatment. Median PFS for the first treatment was
      8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio
      (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no
      difference for median PFS for the second treatment. The HR for overall survival
      was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank,
      P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse
      effects and with increased levels of IgG and cytotoxic-T cell responses to the
      vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in
      PSA-based PFS as compared to the standard-dose EMP alone.

PMID- 20146064
TI  - A retrospective study on 226 polycythemia vera patients: impact of median
      hematocrit value on clinical outcomes and survival improvement with anti
      thrombotic prophylaxis and non-alkylating drugs.
AB  - The clinical impact of polycythemia vera (PV) diagnostic and therapeutic
      guidelines is still undetermined. In particular, the recommended target of
      hematocrit (Hct) <0.45 has been recently questioned and alkylating drugs are
      still used for elderly patients. We revised, according to WHO criteria, 300 PV
      diagnosis and evaluated the impact on clinical outcome of median Hct and of the
      strategy to administer anti-thrombotic prophylaxis and to avoid alkylating
      chemotherapy in almost all patients. Of 226 patients with WHO-confirmed diagnosis
      (median age 66), 91.3% survived at the median follow-up of 5.84 years and 77.5%
      are projected alive at 13 years. Eighteen percent had major thrombosis and 2.7%
      acute myeloid leukemia. Twenty-two percent of patients maintained an Hct <0.45:
      their overall and thrombosis-free survival are similar to those of patients with
      a 0.45-0.48 value. Conversely, an Hct >0.48 and a "high thrombotic risk"
      according to ECLAP criteria were both significantly associated to shorter
      survival and higher thrombosis risk. Chemotherapy reduced thrombotic events
      without affecting survival. Our study revealed suboptimal compliance to published
      guidelines. However, in our casistic characterized by wide use of anti-platelet-
      and avoidance of alkylating drugs, patients' survival, although analyzed
      retrospectively, seemed to have improved compared to old literature data. The
      optimal Hct target was not clearly defined, although a value <0.48 looks highly
      advisable.

PMID- 20146066
TI  - MDCT findings of extrapancreatic nerve plexus invasion by pancreas head
      carcinoma: correlation with en bloc pathological specimens and diagnostic
      accuracy.
AB  - OBJECTIVE: To elucidate the multi-detector row computed tomography (MDCT)
      findings of extrapancreatic nerve plexus (PLX) invasion by pancreas head
      carcinoma (PhC) by "point-by-point" correlation with en bloc pathological
      specimens and to assess their diagnostic accuracy. METHODS: Each pathological
      section of PhC and adjusted double oblique multiplanar reconstruction MDCT images
      were correlated in 554 sections from 37 patients. The diagnostic accuracy of the
      MDCT patterns derived was assessed by blind reading. RESULTS: PLX invasion with
      fibrosis showed mass or strand shape (85.6%) or coarse reticula (13.3%). The CT
      findings were divided into fine reticular and linear, coarse reticular, mass and
      strand, and nodular patterns. PLX invasion was revealed pathologically in 92% of
      the regions of investigation showing the mass and strand pattern and 63% of the
      coarse reticular pattern (all continuous with PhC), and they were highly
      suggestive of PLX invasion by PhC on MDCT images (p < 0.001). Sensitivity,
      specificity, accuracy, and positive and negative predictive values of these MDCT
      findings in the diagnosis of PLX invasion were 100% (25/25), 83.3% (10/12), 94.6%
      (35/37), 92.6% (25/27) and 100% (10/10), respectively. CONCLUSION: The mass and
      strand pattern and the coarse reticular pattern continuous with PhC on MDCT
      images were highly suggestive of PLX invasion by PhC.

PMID- 20146065
TI  - SLAM family receptors and the SLAM-associated protein (SAP) modulate T cell
      functions.
AB  - One or more of the signaling lymphocytic activation molecule (SLAM) family
      (SLAMF) of cell surface receptors, which consists of nine transmembrane proteins,
      i.e., SLAMF1-9, are expressed on most hematopoietic cells. While most SLAMF
      receptors serve as self-ligands, SLAMF2 and SLAMF4 use each other as counter
      structures. Six of the receptors carry one or more copies of a unique
      intracellular tyrosine-based switch motif, which has high affinity for the single
      SH2-domain signaling molecules SLAM-associated protein and EAT-2. Whereas SLAMF
      receptors are costimulatory molecules on the surface of CD4+, CD8+, and natural
      killer (NK) T cells, they also involved in early phases of lineage commitment
      during hematopoiesis. SLAMF receptors regulate T lymphocyte development and
      function and modulate lytic activity, cytokine production, and major
      histocompatibility complex-independent cell inhibition of NK cells. Furthermore,
      they modulate B cell activation and memory generation, neutrophil, dendritic
      cell, macrophage and eosinophil function, and platelet aggregation. In this
      review, we will discuss the role of SLAM receptors and their adapters in T cell
      function, and we will examine the role of these receptors and their adapters in X
      linked lymphoproliferative disease and their contribution to disease
      susceptibility in systemic lupus erythematosus.

PMID- 20146067
TI  - Beneficial effect of delayed reperfusion in ST elevation myocardial infarction
      despite transmural necrosis documented in cardiac magnetic resonance imaging.

PMID- 20146068
TI  - Mutation analysis of Parkin, PINK1 and DJ-1 genes in Chinese patients with
      sporadic early onset parkinsonism.
AB  - Early onset parkinsonism (EOP) has been associated with mutations in the Parkin,
      PINK1, and DJ-1 genes. We studied the prevalence of mutations in all three genes
      in 127 unrelated Chinese patients with apparently sporadic EOP using direct
      sequencing analysis and real-time quantitative PCR analysis assay. There are 16
      patients (12.6%) with mutations of Parkin gene, four patients (3.1%) with
      mutations of PINK1 gene, and three patients (2.4%) with mutation of DJ-1 gene. In
      conclusion, Parkin gene mutation is the most common pathogenic factor in Chinese
      patients with sporadic EOP. Mutations of DJ-1 and PINK1 gene are also found in
      Chinese patients with sporadic EOP.

PMID- 20146069
TI  - Slow saccades in bulbar-onset motor neurone disease.
AB  - Historical studies of eye movements in motor neurone disease (MND) have been
      conflicting although current findings suggest that eye movement abnormalities
      relate to frontal lobe impairment. Numerous case reports, however, describe slow
      saccades and supranuclear gaze palsies in patients with MND often associated with
      bulbar-onset disease. We performed a study of saccades and smooth pursuit in a
      large group of patients with MND to examine for any differences between bulbar
      onset and spinal-onset patients. Forty-four patients (14 bulbar-onset and 30
      spinal-onset patients) and 45 controls were recruited. Reflexive saccades,
      antisaccades and smooth pursuit were examined using infra-red oculography and all
      subjects then underwent neuropsychological evaluation. Reflexive saccades were
      found to be slower in bulbar-onset compared to spinal-onset patients and controls
      (p = 0.03, p = 0.05). Antisaccade latency (p = 0.01) and antisaccade type 1
      errors (p = 0.03, p = 0.04) were increased in patients compared to controls.
      'Proportion of time spent in smooth pursuit' and smooth pursuit 'velocity gain'
      were reduced in patients compared to controls (p = 0.000, p = 0.001). Antisaccade
      errors and velocity gain correlated with neuropsychological measures sensitive to
      lesions of the frontal lobes. This is the first study to highlight the presence
      of slow saccades in bulbar-onset MND. These findings suggest that slow saccades
      may be due to increased brainstem pathology in bulbar-onset disease that involves
      burst cell neurons. Furthermore these observations highlight the potential for
      overlap between bulbar-onset MND and progressive supranuclear palsy (PSP) as both
      can have a bulbar palsy and slowed saccades.

PMID- 20146070
TI  - Facioscapulohumeral muscular dystrophy presenting with unusual phenotypes and
      atypical morphological features of vacuolar myopathy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular
      dystrophy and usually follows an autosomal dominant trait. Clinically, FSHD
      affects facial muscles and proximal upper limb and girdle muscles, but may
      present with variable clinical phenotypes even within the same family. Most
      genetically confirmed FSHD patients exhibit unspecific morphological signs of a
      degenerative myopathy. We report on five unrelated patients who carried the
      pathogenic FSHD mutation on chromosome 4q35. Muscle biopsies revealed numerous
      rimmed vacuoles and filamentous cytoplasmic inclusions in all cases. Clinically,
      the patients suffered from weakness and atrophy predominantly of the lower limb
      muscles. In conclusion, we suggest considering FSHD in the differential diagnosis
      of adult-onset distal myopathies with rimmed vacuoles.

PMID- 20146073
TI  - Time to revisit VEP monitoring?

PMID- 20146071
TI  - Energetic effects of stimulus intensity on prolonged simple reaction-time
      performance.
AB  - The efficiency of cognition is modulated by energetic factors like effort,
      fatigue or circadian variation, which affect even the most basic cognitive
      operations. For instance, speeded detection in simple reaction-time (SRT) tasks
      usually slows down over time. The literature suggests that either mindlessness
      due to routinization or mental fatigue due to attentional resource depletion
      might underlie this decrement. We tested these assumptions in three 25-min visual
      SRT tasks using easy-to-detect high-intensity and hard-to-detect low-intensity
      stimuli presented in both blocked and mixed fashion. Mindlessness theory predicts
      that less monotonous stimulation (i.e. the mixed presentation) would mitigate the
      time-related decrement for high- and low-intensity stimuli alike, whereas
      resource-depletion theory predicts opposite effects of mixed presentation on high
      versus low-intensity stimuli. Indeed, stimulus intensity and presentation mode
      cross-interacted significantly, indicating that the performance decline was
      steeper for high-intensity stimuli but less steep for low-intensity stimuli
      during mixed compared to blocked presentation, respectively. These results
      strongly suggest that the time-related efficiency decrement during prolonged SRT
      performance is related to accumulating mental fatigue. A conjecture is put
      forward that explains both resource depletion and mindlessness from the
      perspective of self-regulation. Our study underscores the need to incorporate
      energetic factors into models of cognition to facilitate their translation into
      real-world applications.

PMID- 20146075
TI  - Variable presentations of Currarino syndrome in three members of the same family.

PMID- 20146076
TI  - Structures and energies of the radicals and anions generated from chlorpyrifos.
AB  - The radicals and anions generated from chlorpyrifos by removing a hydrogen atom
      have been investigated using the hybrid density functional B3PW91 method. The
      results show that all the radicals have been classified as three groups and their
      stability order is methylene (radical 1, 3, 5, and 7) > methyl (radical 9, 11 and
      13) > ring (15); the anions have the relative energetic order: methyl > methylene
      > ring. Moreover, some decomposition reactions are also reported. The large HOMO
      LUMO gaps indicate that both radicals and anions are predicted to be high-kinetic
      stable molecules. We also find that radicals 9, 11 and 13 have the highest AEAs
      and anions 2, 4 and 6 have higher VDEs. Additionally, natural population analysis
      charges show that there is the lowest Deltaq (0.14) for the C7 and C9 atoms. We
      hope that our theoretical results may provide a reference for further experiment
      and practical application.

PMID- 20146077
TI  - Chimpanzees (Pan troglodytes) accurately compare poured liquid quantities.
AB  - Although many studies have shown that nonhuman animals can choose the larger of
      two discrete quantities of items, less emphasis has been given to discrimination
      of continuous quantity. These studies are necessary to discern the similarities
      and differences in discrimination performance as a function of the type of
      quantities that are compared. Chimpanzees made judgments between continuous
      quantities (liquids) in a series of three experiments. In the first experiment,
      chimpanzees first chose between two clear containers holding differing amounts of
      juice. Next, they watched as two liquid quantities were dispensed from opaque
      syringes held above opaque containers. In the second experiment, one liquid
      amount was presented by pouring it into an opaque container from an opaque
      syringe, whereas the other quantity was visible the entire time in a clear
      container. In the third experiment, the heights at which the opaque syringes were
      held above opaque containers differed for each set, so that sometimes sets with
      smaller amounts of juice were dropped from a greater height, providing a possible
      visual illusion as to the total amount. Chimpanzees succeeded in all tasks and
      showed many similarities in their continuous quantity estimation to how they
      performed previously in similar tasks with discrete quantities (for example,
      performance was constrained by the ratio between sets). Chimpanzees could compare
      visible sets to nonvisible sets, and they were not distracted by perceptual
      illusions created through various presentation styles that were not relevant to
      the actual amount of juice dispensed. This performance demonstrated a similarity
      in the quantitative discrimination skills of chimpanzees for continuous
      quantities that matches that previously shown for discrete quantities.

PMID- 20146079
TI  - Thyroid hormone receptor-mediated regulation of the methionine
      adenosyltransferase 1 gene is associated with cell invasion in hepatoma cell
      lines.
AB  - The thyroid hormone T(3) regulates differentiation, growth, and development. We
      demonstrated that methionine adenosyltransferase 1A (MAT1A) was positively
      regulated by T(3) identified by cDNA microarray previously. The expression of the
      MAT1A was upregulated by T(3) in hepatoma cell lines overexpressing thyroid
      hormone receptors (TRs). Additionally, these findings indicate that MAT1A may be
      regulated by CCAAT/enhancer binding protein (C/EBP). The critical role of the
      C/EBP binding sites was confirmed by the reporter or chromatin immuno
      precipitation (ChIP) assay. In addition, C/EBP was upregulated in hepatoma cells
      after T(3) treatment and ectopic expression of MAT1A inhibited cell migration and
      invasion in J7 hepatoma cells. Conversely, knockdown of MAT1A expression
      increased cell migration. Together, these findings suggest that the expression of
      the MAT1A gene is mediated by C/EBP and is indirectly upregulated by T(3).
      Finally, TR was downregulated in a small subset of hepatocellular carcinoma cells
      concomitantly reduced the expression of C/EBPalpha and MAT1A.

PMID- 20146080
TI  - P2X7, NMDA and BDNF receptors converge on GSK3 phosphorylation and cooperate to
      promote survival in cerebellar granule neurons.
AB  - Glycogen synthase kinase-3 (GSK3) is a key player in the regulation of neuronal
      survival. Herein, we report evidence of an interaction between P2X7 receptors
      with NMDA and BDNF receptors at the level of GSK3 signalling and neuroprotection.
      The activation of these receptors in granule neurons led to a sustained pattern
      of GSK3 phosphorylation that was mainly PKC-dependent. BDNF was the most potent
      at inducing GSK3 phosphorylation, which was also dependent on PI3K. The P2X7
      agonist, BzATP, exhibited additive effects with both NMDA and BDNF to rescue
      granule neurons from cell death induced by PI3K inhibition. This survival effect
      was mediated by the PKC-dependent GSK3 pathway. In addition, ERK1/2 proteins were
      also involved in BDNF protective effect. These results show the function of ATP
      in amplifying neuroprotective actions of glutamate and neurotrophins, and support
      the role of GSK3 as an important convergence point for these survival promoting
      factors in granule neurons.

PMID- 20146081
TI  - Role of Chk1 in the differentiation program of hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSC) isolated from umbilical cord blood (UCB) were
      treated with ionizing radiation (IR) and sensitivity and IR induced checkpoints
      activation were investigated. No difference in the sensitivity and in the
      activation of DNA damage pathways was observed between CD133+ HSC and cells
      derived from them after ex vivo expansion. Chk1 protein was very low in freshly
      isolated CD133+ cells, and undetectable in ex vivo expanded UCB CD133+ cells.
      Chk1 was expressed only on day 3 of the ex vivo expansion. This pattern of Chk1
      expression was corroborated in CD133+ cells isolated from peripheral blood
      apheresis collected from an healthy donor. Treatment with a specific Chk1
      inhibitor resulted in a strong reduction in the percentage of myeloid precursors
      (CD33+) and an increase in the percentage of lymphoid precursors (CD38+) compared
      to untreated cells, suggesting a possible role for Chk1 in the differentiation
      program of UCB CD133+ HSC.

PMID- 20146082
TI  - Leptomeningeal gliomatosis as the initial presentation of gliomatosis cerebri.
AB  - Leptomeningeal gliomatosis is a known, yet uncommon, complication of malignant
      gliomas. In rare instances it can present with non-specific symptoms prior to the
      development of detectable intraparenchymal lesions, posing a diagnostic
      challenge. Gliomatosis cerebri is also a rare disease, characterized by extensive
      diffuse infiltration of neoplastic glial cells. For both entities, limited data
      exist to guide treatment and prognosis is poor. We describe the case of a patient
      who presented with symptoms of increased intracranial pressure and diffuse
      leptomeningeal enhancement in the brain and spinal cord on MRI. After a period of
      surveillance, intraparenchymal lesions developed in association with widespread
      diffuse infiltration. The diagnosis of gliomatosis cerebri with diffuse
      leptomeningeal gliomatosis was established in hindsight. Initial treatment
      consisted of six cycles of temozolomide chemotherapy. Following radiological
      progression, the patient received craniospinal radiotherapy. Four months later
      the patient's symptoms had resolved and MRI demonstrated near complete response
      of leptomeningeal enhancement and intraparenchymal lesions. Six months after
      radiotherapy, the patient remains clinically well without radiographic
      recurrence.

PMID- 20146083
TI  - Cranial vault lymphoma: a systematic review of five patients.
AB  - Bone involvement is a common finding in many types of lymphoma (Clin Oncol 9(3):
      195-196, 1997). However, cranial vault affliction has been regarded as an
      exceedingly rare presentation, particularly in the case of primary lymphoma (J
      Neurosurg 108(5): 1018-1020, 2008). Our objective is to describe a series of five
      immunocompetent patients with histologically confirmed cranial vault lymphoma
      (CVL), and to conduct a systematic review of the current literature. Our review
      points out identical imaging patterns in most of the lesions for all reported CVL
      cases, despite their different histological subtypes. This typical pattern can be
      seen on computed tomography (CT) scans and magnetic resonance imaging (MRI) as an
      expansive tumor that affects all three compartments of the cranial vault,
      including the scalp, skull bone, and pachymeninges, even in the absence of
      osteolysis. We argue that the absence of osteolysis might enhance diagnostic
      capability. In the appropriate clinical setting, these features represent
      important disease characteristics that may help with an earlier diagnosis. Large
      B-cell lymphoma was the most common subtype of primary CVL.

PMID- 20146084
TI  - Integration of autologous dendritic cell-based immunotherapy in the primary
      treatment for patients with newly diagnosed glioblastoma multiforme: a pilot
      study.
AB  - Despite resection, radiochemotherapy, and maintenance temozolomide chemotherapy
      (TMZm), the prognosis of patients with glioblastoma multiforme (GBM) remains
      poor. We integrated immunotherapy in the primary standard treatment for eight
      pilot adult patients (median age 50 years) with GBM, to assess clinical and
      immunological feasibility and toxicity in preparation of a phase I/II protocol
      HGG-2006. After maximum, safe resection, leukapheresis was performed before
      radiochemotherapy, and four weekly vaccinations with autologous GBM lysate-loaded
      monocyte-derived dendritic cells were given after radiochemotherapy. Boost
      vaccines with lysates were given during TMZm. During the course of vaccination,
      immunophenotyping showed a relative increase in CD8+CD25+ cells in six of the
      seven patients, complying with the prerequisites for implementation of
      immunotherapy in addition to postoperative radiochemotherapy. In five patients, a
      more than twofold increase in tumor antigen-reacting IFN-gamma-producing T cells
      on Elispot was seen at the fourth vaccination compared with before vaccination.
      In three of these five patients this more than twofold increase persisted after
      three cycles of TMZm. Quality of life during vaccination remained excellent.
      Progression-free survival at six months was 75%. Median overall survival for all
      patients was 24 months (range: 13-44 months). The only serious adverse event was
      an ischemic stroke eight months postoperatively. We conclude that tumor
      vaccination, fully integrated within the standard primary postoperative treatment
      for patients with newly diagnosed GBM, is feasible and well tolerated. The
      survival data were used to power a currently running phase I/II trial.

PMID- 20146085
TI  - Multiple paraneoplastic diseases occurring in the same patient after
      thymomectomy.
AB  - Thymoma-associated paraneoplastic diseases include myasthenia gravis (MG),
      neuromyotonia (NMT), Morvan's syndrome, and several non-neurological
      paraneoplastic manifestations, including glomerulonephritis. Paraneoplastic
      syndromes often precede the occurrence of thymoma, but cases occurring after
      thymomectomy, which sometimes herald the recurrence of thymoma, have also been
      described. We report on a patient who developed MG after thymomectomy for a
      malignant thymoma. After MG remission, NMT and Morvan's syndrome occurred, which
      heralded a mediastinic recurrence, as demonstrated only by autopsy findings.

PMID- 20146086
TI  - High dose weekly erlotinib achieves therapeutic concentrations in CSF and is
      effective in leptomeningeal metastases from epidermal growth factor receptor
      mutant lung cancer.
AB  - Leptomeningeal metastases (LM) occur in 5-10% of patients with solid tumors and
      are associated with a dismal prognosis. We describe LM from lung adenocarcinoma
      harboring a mutation in the epidermal growth factor receptor (EGFR) gene that
      confers sensitivity to the EGFR tyrosine kinase inhibitors (EGFR-TKIs) erlotinib
      and gefitinib. The CSF concentration of EGFR-TKIs achieved by standard daily
      dosing may be insufficient for therapeutic effect. However, intermittent
      (pulsatile) high dose administration (1000-1500 mg/week) achieves a higher CSF
      concentration than standard dosing, and successfully controlled LM in this
      patient.

PMID- 20146087
TI  - A prospective evaluation and literature review of levetiracetam use in patients
      with brain tumors and seizures.
AB  - To determine the safety and tolerability of IV and oral levetiracetam monotherapy
      for seizures in brain tumor patients following resection. Brain tumor patients
      undergoing neurosurgery with >or=1 seizure within the preceding month prior to
      surgery were enrolled to receive intravenous levetiracetam for a minimum of 48 h,
      transitioned to oral levetiracetam at the same dose, and followed for 1-month
      after discharge. Patients were assessed daily in the hospital, provided with a
      seizure diary, and supplied with 30 days of levetiracetam upon discharge. Study
      patients were telephoned weekly to assess their cognitive status and seizure
      frequency. Of the 17 patients enrolled, the baseline seizure types were tonic
      clonic, partial, and complex partial with secondary generalization. The most
      common type of tumor was glioblastoma multiforme. Levetiracetam was well
      tolerated with no medication discontinuation during the study period. Adverse
      effects reported were somnolence, nausea/vomiting, headache, and insomnia. Eleven
      patients were evaluable for TICS scores (64.7%) with an average score of 33.3.
      Two patients were deemed to be cognitively impaired (18.2%). Eleven of twelve
      patients (91.7%) that completed the study period achieved a >or=50% reduction in
      their number of seizures. A total of 92 drug interactions were avoided (P =
      0.0016) with dexamethasone, acetaminophen, and fentanyl being the most common.
      Levetiracetam monotherapy was found to be safe and tolerable in this patient
      population. Nearly all patients achieved a >or=50% reduction in seizure frequency
      post-op with levetiracetam monotherapy. Levetiracetam also has the potential for
      less drug interactions compared to phenytoin in these patients.

PMID- 20146088
TI  - Bradykinin increases the permeability of the blood-tumor barrier by the caveolae
      mediated transcellular pathway.
AB  - Bradykinin (BK) increases the permeability of the blood-tumor barrier (BTB)
      selectively through the transcellular pathway; however, the role of the caveolae
      structural proteins caveolin-1 and caveolin-2 in this process has not been
      precisely elucidated. Thus, this study was performed to examine whether caveolin
      1 and caveolin-2 are involved in the regulation of this biological process. In
      the rat brain glioma (C6) model, western blot, immunohistochemistry, and
      immunofluorescence assays were used to detect the expression levels and locations
      of caveolin-1 and caveolin-2. The results showed that caveolin-1 and caveolin-2
      levels increased 5 min after BK infusion, peaked at 15 min, and then decreased.
      Meanwhile, Evans blue (EB) assay showed that the permeability of the BTB
      increased significantly after BK infusion. In our previous study we demonstrated
      that the quantity of pinocytotic vesicles in the endothelial cells was
      dramatically augmented 15 min after BK infusion. The time point at which changes
      of caveolin-1 and caveolin-2 reached their peak was the same as that at which EB
      and the quantity of pinocytotic vesicles reached their peaks. This led to the
      conclusion that the BK-mediated BTB permeability increase resulting from
      augmentation of the quantity of pinocytotic vesicles (transcellular pathway) is
      associated with the significantly up-regulated expression of caveolin-1 and
      caveolin-2. This study thus contributes further to elucidating the molecular
      mechanism of opening of the BTB by BK and provides a theoretical basis for
      clinical application of BK.

PMID- 20146089
TI  - Primary central nervous system Burkitt lymphoma as concomitant lesions in the
      third and the left ventricles: a case study and literature review.
AB  - This study reports the case of a 75-year-old woman with intermittent speech
      disturbance, headache, and general malaise. Brain magnetic resonance imaging
      showed a double lesion located in the third ventricle and temporal horn of the
      lateral ventricle. We completely removed the lesion in the third ventricle,
      adhering to the septum pellucidum. The histopathological diagnosis was Burkitt
      lymphoma, which was confirmed to be primary in postoperative investigation. To
      our knowledge, this is the first case of primary Burkitt lymphoma involving
      cerebral ventricles. Finally, we reviewed the characteristics of primary central
      nervous system Burkitt lymphoma.

PMID- 20146090
TI  - Biodegradation of the major color containing compounds in distillery wastewater
      by an aerobic bacterial culture and characterization of their metabolites.
AB  - This study deals the biodegradation of the major color containing compounds
      extracted from distillery wastewater (DWW) by an aerobic bacterial consortium
      comprising Bacillus licheniformis (DQ79010), Bacillus sp. (DQ779011) and
      Alcaligenes sp. (DQ779012) and characterization of metabolic products. The
      degradation of color containing compounds by bacteria was studied by using the
      different carbon and nitrogen sources at different environmental conditions.
      Results revealed that the bacterial consortium was efficient for 70% color
      removal in presence of glucose (1.0%) and peptone (0.1%) at pH 7.0 and
      temperature 37 degrees C. The HPLC analysis of control and bacterial degraded
      samples has shown the reduction in peak area as well as shifting of peaks
      compared to control indicating the bacterial degradation as well as
      transformation of color containing compounds from DWW. The comparative LC-MS-MS
      and other spectrophotometric analysis has shown the presence of
      dihydroxyconiferyl alcohol, 2, 2'-bifuran-5-carboxylic acid, 2-nitroacetophenone,
      p-chloroanisol, 2, 3-dimethyl-pyrazine, 2-methylhexane, methylbenzene, 2, 3
      dihydro-5-methylfuran, 3-pyrroline, and acetic acid in control samples that were
      biodegraded and biotransformed into 2-nitroacetophenone, p-chloroanisol, 2, 2'
      bifuran, indole, 2-methylhexane, and 2, 3-dihydro-5-methylfuran by bacterial
      consortium. In this study, it was observed that most of the compounds detected in
      control samples were diminished from the bacterial degraded samples and compounds
      2, 2'-bifuran and indole with molecular weight 134 and 117 were produced as new
      metabolites during the bacterial degradation of color containing compounds from
      DWW.

PMID- 20146091
TI  - A small grants program to involve communities in research.
AB  - A key tenet of community-based participatory research is that communities be
      involved in all facets of research, from defining the problem to identifying
      solutions, to assisting in the research, and to participating in the publication
      of results. In this study, we instituted a small grants program for community
      participation. A Request for Applications (RFA) was developed and circulated
      widely throughout the Valley. The RFA sought proposals to address health
      disparities in cancer education, prevention, and treatment among Hispanics living
      in the Valley. Funds available were $2,500.00-3,500.00 for 1 year's worth of
      work. To help evaluate the progress of the RFA community projects according to
      the perspectives of the Community Advisory Board (CAB), an open-ended, semi
      structured interview was created and administered by a former staff member to CAB
      members. In 4 years, ten small grants proposed by community members were funded.
      Funds allocated totaled approximately $25,000. Interviews with CAB members
      indicated that the RFA program was perceived positively, but there were concerns
      about sustainability. Our community grants program resulted in the implementation
      of several novel cancer prevention programs conducted by a variety of community
      organizations in the Lower Yakima Valley.

PMID- 20146092
TI  - Need to improve routine HIV testing of U.S. Veterans in care: results of an
      Internet survey.
AB  - Late diagnosis of HIV infection contributes to poor medical outcomes and helps
      sustain continued transmission of virus. Published evidence suggests that despite
      current public health recommendations, patients receiving care in the Veterans
      Health Administration (VHA) system are not being routinely tested for HIV
      infection. Using a sample of computer-literate veterans, we conducted a survey of
      recent testing experiences. My HealtheVet (MHV) is a secure website allowing
      registered Veterans to access limited personal VHA health information. Using the
      American Customer Satisfaction Index (ACSI) Survey, an electronic questionnaire
      on "health screening" was conducted in late Fall/early winter 2008-2009. A random
      sample (4%) of MHV users were surveyed; approximately 17% completed the survey
      and responses ranged from 31,237 to 33,074. Only 9% of the respondents indicated
      that they had been offered a test for HIV in the last 12 months compared to 83%
      who had been offered cholesterol screening, 65% blood sugar screening and 19% who
      had been offered testing for Hepatitis C virus (HCV). Of those who had been
      offered HIV testing, 91% indicated that they'd had the test performed. Of note,
      the percentage of respondents who indicated that they would "very likely" accept
      a test, if offered, was similar for HIV (73%), HCV (79%), cholesterol (75%), and
      blood sugar (75%). Although these results cannot be generalized to all Veterans
      in care, they suggest that routine testing for HIV has not been taking place and
      support recent VHA policy changes to remove barriers to HIV testing.

PMID- 20146093
TI  - Exercises in emergency preparedness for health professionals in community
      clinics.
AB  - Health professionals in community settings are generally unprepared for
      disasters. From 2006 to 2008 the California Statewide Area Health Education
      Center (AHEC) program conducted 90 table top exercises in community practice
      sites in 18 counties. The exercises arranged and facilitated by AHEC trained
      local coordinators and trainers were designed to assist health professionals in
      developing and applying their practice site emergency plans using simulated
      events about pandemic influenza or other emergencies. Of the 1,496
      multidisciplinary health professionals and staff participating in the exercises,
      1,176 (79%) completed learner evaluation forms with 92-98% of participants rating
      the training experiences as good to excellent. A few reported helpful effects
      when applying their training to a real time local disaster. Assessments of the
      status of clinic emergency plans using 15 criteria were conducted at three
      intervals: when the exercises were scheduled, immediately before the exercises,
      and for one-third of sites, three months after the exercise. All sites made
      improvements in their emergency plans with some or all of the plan criteria. Of
      the sites having follow up, most (N = 23) were community health centers that made
      statistically significant changes in two-thirds of the plan criteria (P = .001
      .046). Following the exercises, after action reports were completed for 88 sites
      and noted strengths, weaknesses, and plans for improvements in their emergency
      plans Most sites (72-90%) showed improvements in how to activate their plans, the
      roles of their staff, and how to participate in a coordinated response.
      Challenges in scheduling exercises included time constraints and lack of
      resources among busy health professionals. Technical assistance and
      considerations of clinic schedules mitigated these issues. The multidisciplinary
      table top exercises proved to be an effective means to develop or improve clinic
      emergency plans and enhance the dialogue and coordination among health
      professionals before an emergency happens.

PMID- 20146094
TI  - Genomic characterization of the first class I Newcastle disease virus isolated
      from the mainland of China.
AB  - The complete genomic sequence of Newcastle disease virus (NDV) strain NDV08-004,
      isolated from domestic ducks in China, was determined in this study. The genome
      is 15198 nucleotides (nt) in length, follows the "rule of six" and contains a 55
      nt leader sequence at the 3' end and a 114-nt trailer sequence at the 5' end.
      Compared with the full genome sequences of Class II NDV strains, the NDV08-004
      isolate has a 12-nt insertion (TGGGAGACGGGG) in the phosphoprotein gene between
      nucleotides 2381 and 2382 of the genome (numbered according to the genomic
      sequence of the La Sota strain, which consists of 15186 nt). Strain NDV08-004 has
      the motif (112)E-Q-Q-E-R-L(117) at the cleavage site of the fusion protein, which
      is typical of lentogenic NDV strains, and this is in agreement with the results
      of pathogenic tests based on the mean death time (MDT) and the intracerebral
      pathogenicity index (ICPI). Phylogenetic analysis based on the full genome
      revealed that all the NDV strains studied could be divided into two distinct
      clades, namely class I and class II, and the NDV08-004 isolate characterized in
      this study was grouped in class I. Further phylogenetic analysis based on a 374
      bp fragment of the F gene in class I strains of NDV demonstrated that NDV08-004
      belongs to genotype 3, and should be therefore similar to strains obtained from
      live bird markets in Hong Kong in recent years.

PMID- 20146096
TI  - Likert scales, levels of measurement and the "laws" of statistics.
AB  - Reviewers of research reports frequently criticize the choice of statistical
      methods. While some of these criticisms are well-founded, frequently the use of
      various parametric methods such as analysis of variance, regression, correlation
      are faulted because: (a) the sample size is too small, (b) the data may not be
      normally distributed, or (c) The data are from Likert scales, which are ordinal,
      so parametric statistics cannot be used. In this paper, I dissect these
      arguments, and show that many studies, dating back to the 1930s consistently show
      that parametric statistics are robust with respect to violations of these
      assumptions. Hence, challenges like those above are unfounded, and parametric
      methods can be utilized without concern for "getting the wrong answer".

PMID- 20146095
TI  - Personality mediation of genetic effects on Attention-Deficit/Hyperactivity
      Disorder.
AB  - Personality traits may be viable candidates for mediators of the relationship
      between genetic risk and ADHD. Participants were 578 children (331 boys; 320
      children with ADHD) between the ages of six and 18. Parents and teachers
      completed a comprehensive, multi-stage diagnostic procedure to assess ADHD and
      comorbid disorders. Mother completed the California Q-Sort to assess child Big
      Five personality traits. Children provided buccal samples of DNA which were
      assayed for selected markers on DRD4, DAT1, and ADRA2A. An additive genetic risk
      composite was associated with ADHD symptoms and maladaptive personality traits;
      maladaptive personality traits were associated with ADHD symptoms. Low
      conscientiousness and high neuroticism partially mediated the relationship
      between genetic risk and ADHD symptoms. Mediation effects for conscientiousness
      were specific to inattentive symptoms; effects for neuroticism generalized to all
      disruptive behaviors. High neuroticism and low conscientiousness may be useful as
      early markers for children at risk for ADHD.

PMID- 20146097
TI  - An examination of treatment completers and non-completers at a child and
      adolescent community mental health clinic.
AB  - This study examined sociodemographic and clinical characteristics of treatment
      completers (N = 114) and non-completers (N = 136) at a child and adolescent
      community mental health clinic. Results indicated that children who completed
      treatment significantly differ from those who prematurely drop out of treatment.
      Non-completers presented with considerably more impairment in functioning and
      psychiatric symptoms, and their caregiver reported experiencing significantly
      more parenting stress and depressive symptoms. Results suggest that mental health
      treatment is not readily provided to the most difficult to reach and most at-risk
      youth and their families.

PMID- 20146098
TI  - Post natal use of analgesics: comparisons between conventional postnatal wards
      and a maternity hotel.
AB  - AIM: To investigate factors related to analgesic use after delivery, and
      especially whether rates of analgesic use were different in a midwife-managed
      maternity hotel as compared to conventional postnatal wards. SETTING: One
      maternity hotel and two conventional postnatal wards at Ulleval University
      Hospital in Oslo, Norway. METHOD: Data were obtained from hospital records for
      804 women with vaginal deliveries. MAIN OUTCOME MEASURE: Postnatal analgesic use.
      RESULTS: Overall, approximately half the women used analgesics after vaginal
      delivery in both conventional postnatal wards and maternity hotel. The factors
      that were significantly associated with use of analgesics postnatally in
      multivariate analysis were multiparity, having a non-Western ethnicity, smoking
      in pregnancy, younger age, instrumental delivery, analgesic use during labour,
      maternal complications post partum, and duration of postnatal stay 4 days or
      more. CONCLUSION: The use of analgesics is determined by socio-demographic and
      obstetric factors rather than the organisation of the ward.

PMID- 20146099
TI  - Primary pituitary lymphoma in immunocompetent patient: diagnostic problems and
      prolonged follow-up.
AB  - Primary pituitary lymphoma in immunocompetent patients is a rare disease and has
      been described in less than 20 cases. Moreover, low-grade lymphomas constitute
      only 3% of all primary central nervous system lymphoma. The objective of this
      report is to report a low-grade primary pituitary lymphoma, diagnostic problems
      and to give more evidence about the evolution of this rare disease. A 49 y.o.
      woman was referred to our clinic with symptoms of hypopituitarism. A diagnostic
      work-up showed mild anemia, an erythrocyte sedimentation rate of 122 mm/h and a
      negative Elisa test for HIV. Panhypopituitarism was confirmed and the MRI showed
      a 20 mm sellar and suprasellar enhancing mass with a thickening of the pituitary
      stalk, chiasmal compression and bitemporal hemianopsia. She underwent
      transsphenoidal resection only 10 months later for non medical reasons. During
      this period she was clinically asymptomatic on hormonal replacement therapy. A
      new MRI showed regression of the suprasellar extension and invasion to the left
      cavernous sinus. A firm and infiltrative mass was found during transsphenoidal
      surgery, and only partial resection was performed. Biopsy showed a low-grade
      lymphoplasmacytic lymphoma. Staging was negative for other localizations. She was
      given chemotherapy and localized radiotherapy. Four years after surgery, the
      sellar MRI showed a 10 mm residual sellar mass with the persistence of a
      cavernous sinus invasion and she is considered to be in remission. The
      neurosurgeon and clinician should consider primary pituitary lymphoma as a
      potential cause of a sellar mass, especially in the presence of diabetes
      insipidus and an enhancing invasive mass. Neurosurgical biopsy is crucial for a
      correct diagnosis and prognosis could be better than classic CNS primary
      lymphomas.

PMID- 20146100
TI  - Prophylactic lymphadenectomy of neck level II in clinically node-positive
      papillary thyroid carcinoma.
AB  - BACKGROUND: The purpose of this study was to examine the frequency, pattern, and
      predictive factors associated with occult level II lymph node (LN) metastases in
      papillary thyroid carcinoma (PTC) patients with clinically metastatic lymph nodes
      in the lateral neck (level III, IV, and/or V) by preoperative ultrasonography.
      METHODS: We retrospectively reviewed the medical records of 52 PTC patients with
      clinically positive neck lymph nodes in level III, IV, and/or V based on
      preoperative ultrasonography, who underwent therapeutic lateral neck dissection
      (ND) (level II-V) between March 2004 and October 2009. All patients had no
      suspicion of clinically positive neck nodes in level II. Histopathological
      analysis of neck specimens according to each node level of the neck was
      performed, with special attention given to level II. RESULTS: Forty-two (81%), 41
      (79%), and 6 (12%) patients had histologically positive lymph nodes in level III,
      IV, and V, respectively. Occult metastases in level II were observed in ten (19%)
      patients. Patients without suspicious positive LNs in both neck level III and IV
      by preoperative ultrasonography, and patients without pathologic LN metastases in
      level III, had no occult LN metastases occurrence to level II. Based on
      multivariate analysis, presence of more than four metastatic LNs was an
      independent predictive factor for occult level II metastases [P = 0.022, odds
      ratio (OR) = 7.738]. CONCLUSIONS: Prophylactic level II LN dissection may be
      omitted in PTC patients with clinically positive neck nodes if suspicious
      positive lymph nodes in level III are absent during preoperative ultrasonography.

PMID- 20146101
TI  - An evaluation of the number of lymph nodes examined and survival for node
      negative esophageal carcinoma: data from China.
AB  - BACKGROUND: The current American Joint Committee on Cancer (AJCC) staging system
      for esophageal cancer does not define the minimum number of lymph nodes (LNs)
      necessary for accurate nodal staging. This study aimed to seek the minimum number
      of LNs examined for adequate nodal staging of patients with node-negative
      esophageal cancer. METHODS: We conducted a retrospective review of 592 patients
      undergoing R0 resection with node-negative esophageal carcinoma between December
      1996 and December 2004. The relationship between the total number of examined LNs
      and death from esophageal cancer was investigated by means of a scatterplot of
      this variable versus Martingale residuals from a Cox proportional hazard
      regression model without the variable of interest. A smoothed line fit of the
      scatterplot was applied to detect the reasonable cutoff point. RESULTS: The
      patients were classified into four categories according to the number of examined
      LNs: < or =5, 6 to 9, 10 to 17, and > or =18. A reduced hazard ratio of death was
      observed with an increasing number of LNs examined. The 5-year cancer-specific
      survival rate was 42.8% among patients with < or =5 LNs examined, compared with
      52.6, 56.8, and 75% for those with 6-9 LNs, 10-17 LNs, and > or =18 LNs,
      respectively. Multivariate Cox regression analysis suggested that female sex,
      lower grade of cell differentiation, lower T category and increasing number of
      examined LNs were independent factors favoring cancer-specific survival.
      CONCLUSIONS: At least 18 LNs should be resected for accurate staging of operable
      esophageal carcinoma. However, a validation from other institute is warranted.

PMID- 20146102
TI  - Long-term single-center results of management of ethmoid adenocarcinoma: 95
      patients over 28 years.
AB  - OBJECTIVES: To assess management options for ethmoid adenocarcinoma. STUDY
      DESIGN: Retrospective review over 28 years. PATIENTS AND METHODS: Ninety-five
      patients were included. Statistical analysis using the Kaplan-Meier method was
      performed to establish survival rates, and univariate analysis to determine
      prognostic factors. Independent chi(2) test was used to compare survival rates
      between T3 and T4a stages operated by transfacial and craniofacial approaches,
      respectively. RESULTS: Mean age was 64 years, and 76% patients were stage T3 or
      T4. Three patients had node metastasis, none of whom had distant metastases at
      time of diagnosis. Eighty-three percent of patients received surgery and adjuvant
      radiotherapy on tumor bed. Mean follow-up was 5 years. The recurrence and
      metastasis rate were 31 and 9% at median time of 3 years, respectively. The
      disease-specific 5- and 10-year survival rates were 78 and 64%, respectively. The
      disease-free survival rate was 61 and 44%, respectively, at the same time points.
      Meningo-encephalic (P = 10(-8)), orbit or infratemporal fossae (P = 0.046), and
      frontal sinus extension (P = 0.02) negatively impacted survival. There was no
      statistically significant difference in survival rate between T3 and T4a.
      CONCLUSIONS: Our data suggest that less surgical treatment may be needed than is
      usually advocated for T1-T4a tumors and that surgery alone may be appropriate for
      T1-T3 tumors that have been resected with adequate margins in those patients for
      whom excellent follow-up is anticipated. No neck irradiation is indicated for N0
      disease.

PMID- 20146103
TI  - Clinical implication and mitotic effect of CD44 cleavage in relation to
      osteopontin/CD44 interaction and dysregulated cell cycle protein in
      gastrointestinal stromal tumor.
AB  - BACKGROUND: CD44 and osteopontin (OPN) are functionally related molecules that,
      alone or in combination, play miscellaneous biological and pathophysiologic
      roles. CD44 cleavage, one unique feature of CD44, occurs in human cancers, but
      its function remains unclear. This study aimed to assess the clinicopathologic
      significance and mechanism of CD44 cleavage in gastrointestinal stromal tumor
      (GIST) with respect to OPN and OPN/CD44 interaction. MATERIALS AND METHODS: CD44
      cleavage was evaluated by immunoblotting in 31 primary GIST tumor specimens with
      paired normal tissues. OPN/CD44 interaction was examined by in situ proximity
      ligation assay. The associations of CD44 cleavage activity with clinicopathologic
      parameters, cyclin D1 expression, beta-catenin expression, OPN expression, and
      OPN/CD44 interaction were analyzed. RESULTS: CD44 cleavage activity was
      demonstrated in 87.1% of GIST, in contrast to its absence in normal tissues.
      Increased CD44 cleavage activity was significantly associated with enhanced
      mitosis by multivariate analysis, in addition to being related to tumor size,
      recurrence, high-risk status, and poor survival by univariate analysis. Mitosis
      was significantly higher in GIST with increased CD44 cleavage activity, which
      also positively correlated with tumor-specific beta-catenin and cyclin D1
      overexpression, indicating a mitotic effect through aberrant cell cycle. Both OPN
      and OPN/CD44 interactions were significantly associated with CD44 cleavage.
      CONCLUSION: Our study demonstrates the clinicopathological significance of CD44
      cleavage in GIST. There is a significantly increased mitosis associated with CD44
      cleavage in relation to OPN/CD44 interaction and dysregulated cell cycle in GIST.

PMID- 20146104
TI  - Can instruction in engineering ethics change students' feelings about
      professional responsibility?
AB  - How can a course on engineering ethics affect an undergraduate student's feelings
      of responsibility about moral problems? In this study, three groups of students
      were interviewed: six students who had completed a specific course on engineering
      ethics, six who had registered for the course but had not yet started it, and six
      who had not taken or registered for the course. Students were asked what they
      would do as the central character, an engineer, in each of two short cases that
      posed moral problems. For each case, the role of the engineer was successively
      changed and the student was asked how each change altered his or her decisions
      about the case. Students who had completed the ethics course considered more
      options before making a decision, and they responded consistently despite changes
      in the cases. For both cases, even when they were not directly involved, they
      were more likely to feel responsible and take corrective action. Students who
      were less successful in the ethics course gave answers similar to students who
      had not taken the course. This latter group of students seemed to have weaker
      feelings of responsibility: they would say that a problem was "not my business."
      It appears that instruction in ethics can increase awareness of responsibility,
      knowledge about how to handle a difficult situation, and confidence in taking
      action.

PMID- 20146105
TI  - Prognostic significance of telomerase activity and some tumor markers in non
      small cell lung cancer.
AB  - The prognosis of non small cell lung cancer (NSCLC) has remained disappointing
      over the last decades even in localized stages. Numerous prognostic factors have
      been investigated which might select patients for additional treatment. The
      objective of the current study was to assess the prognostic significance of
      telomerase activity, serum anti-p53 antibodies (anti-p53a), c-erbB-2 and CEA in
      patients with NSCLC. The study included 60 patients with histological proven
      NSCLC besides 60 controls (30 smokers and 30 nonsmokers). Patients were divided
      into four stages according to their histopathology. All patients were subjected
      to; determination of telomerase activity by telomeric repeat amplification
      protocol (TRAP) assay in tumor tissue specimens and adjacent normal lung tissues,
      also, determination of preoperative serum anti-p53a, c-erbB-2 and CEA. Telomerase
      activity was detected in 40 of 60 (66.6%) of NSCLC tissue specimens using the
      TRAP assay. As regard the stages, telomerase activity was positive in 5 of 15
      patients (33.3%) with stage I NSCLC, in 11 of 20 patients (55%) with stage II
      NSCLC, in 9 of 10 patients (90%) with stage III NSCLC and in all patients (100%)
      with stage IV NSCLC. More cases of positive telomerase activity were observed in
      the group with advanced disease and in the group with poorly differentiated
      tumors. Telomerase activity was not detected in any normal lung tissue. The
      concentrations of serum anti-p53a, c-erbB-2, CEA were significantly higher in
      patients with NSCLC in comparison to the smoker and nonsmoker controls and their
      levels increased according to the stage of disease. Logistic regression test
      showed a relation between telomerase positivity and anti- p53a but no relation
      with c-erbB2, CEA. Telomerase activity was detected in most of NSCLC tissues; it
      was detected more frequently in advanced disease than early-stage disease. Anti
      p53, c-erbB-2 and CEA were significantly higher in patients with NSCLC than
      controls and this increment was more evident in late stages of the disease. So,
      these biological markers might be useful predictors of prognosis. They may be
      helpful in defining groups of patients with NSCLC who could benefit from adjuvant
      treatments, also these markers can be used as therapeutic targets.

PMID- 20146106
TI  - Ascitic fluid and serum from rats with acute pancreatitis injure rat pancreatic
      tissues and alter the expression of heat shock protein 60.
AB  - Acute pancreatitis (AP) is an inflammatory process in which cytokines and
      chemokines are involved. After onset, extrapancreatic stimuli can induce the
      expression of cytokines in pancreatic acinar cells, thereby amplifying this
      inflammatory loop. To further determine the role and mechanism of irritating
      agents in the pathogenesis of AP, rat pancreatic tissues were stimulated with
      ascitic fluid (APa) and serum (APs) from rats with AP or with lipopolysaccharide
      (LPS). In addition, the alteration of heat shock protein 60 (HSP60) expression
      was evaluated. Rat pancreas was removed and meticulously snipped to fragments.
      The snips were cultured for up to 48 h. During this period, the tissue viability
      as well as amylase and TNF-alpha levels in the supernatant and the HSP60
      expression in the pancreatic tissue before and after stimulation by APa, APs, and
      LPS were assayed time-dependently. At different time-points during the culture,
      the viability and the amylase activity in the pancreatic tissue remained largely
      stable. After stimulation with APa, APs, or LPS for 1 h, the pancreatic tissues
      showed some damage, and this was followed by a sharp decrease in the viability
      accompanied by increased levels of amylase and TNF-alpha in the culture medium 2
      or 4 h after stimulation (p < 0.05). In contrast, both the HSP60 mRNA and protein
      levels had a relatively high expression in the freshly prepared tissue fragments
      (0 h). As the culturing period was extended, the expression of HSP60 mRNA
      decreased only slightly; at the same time, the HSP60 protein levels decreased
      over a prolonged culture time, significantly so from 12 through 48 h (p < 0.05).
      After stimulation with APs, APa, or LPS, both the expression of HSP60 mRNA and
      protein in the tissue fragments increased slightly at 1 h and decreased
      significantly thereafter at 2 and 4 h (p < 0.05). APa, APs, or LPS induce
      injuries on isolated pancreatic tissues, accompanied by an altered HSP60
      expression pattern in a time-dependent manner.

PMID- 20146110
TI  - Coping strategies of adolescents living with HIV: disease-specific stressors and
      responses.
AB  - This study examined disease-specific stressors and coping responses employed by
      youth with HIV. Data were analyzed from Adolescent Impact, a multi-site study of
      166 adolescents infected with HIV in three major US cities. Participants
      identified HIV-related stressors during a face-to-face interview. Coping
      strategies were measured using the adolescent version of the Kidcope. Emotional
      and behavioral functioning were assessed with the Youth or Adult Self Report
      symptom checklists. Medication-related stressors were most common (30%) and
      reported more often by perinatally infected youth, whereas youth infected through
      risk behaviors reported more disclosure-related stressors. Passive emotional
      regulation was perceived as the most used and most helpful coping strategy
      overall. Youth reporting medication adherence-related stressors used resignation
      most frequently. A two-factor model (Passive and Active Coping) emerged. The
      Passive Coping factor included strategies that do not directly approach the
      problem, whereas Active Coping included strategies that involve an active
      approach. Youth with moderately advanced disease (CD4 200-500 cells/mm(3)) used a
      Passive Coping style more often than healthier youth (CD4 > 500 cells/mm(3)).
      Additionally, Passive Coping was associated with greater emotional and behavioral
      problems. Youth infected with HIV may benefit from interventions promoting
      adaptive coping responses to HIV-specific stressors, particularly medication
      adherence.

PMID- 20146111
TI  - Testing a peer-based symptom management intervention for women living with
      HIV/AIDS.
AB  - OBJECTIVE: To test the impact of participation in a peer-based intervention for
      symptom management for women living with HIV infection on selected outcome
      measures including, symptom intensity, medication adherence, viral control, and
      quality of life. DESIGN: Randomized clinical trial. METHODS: Participants were
      recruited using a convenient, consecutive sampling method. Those participants
      randomized to the experimental condition attended seven, peer-led sessions over
      seven weeks. Participants randomized to the control condition received a copy of
      HIV Symptom Management Strategies: A Manual for People Living with HIV/AIDS.
      Participants completed four surveys assessing change over time in the
      aforementioned outcome variables. RESULTS: Eighty-nine HIV-infected women
      followed over 14 weeks and there were no differences between the two groups on
      baseline demographic variables. Mixed-effects regression indicated no significant
      difference between groups across time in total symptom intensity score and
      medication adherence. There was a significant difference between groups across
      time for two of the nine quality of life scales - HIV Mastery (chi(2)=25.08;
      p<0.005) and Disclosure Worries (chi(2)=24.67; p<0.005). CONCLUSIONS: In urban
      dwelling women living with HIV/AIDS, results suggest that a peer-based symptom
      management intervention may not decrease symptom intensity or increase medication
      adherence. There is positive evidence that suggests that the intervention may
      increase some important aspects of quality of life. However, further research is
      warranted to elucidate the effect of peer-based interventions in achieving
      positive self-management outcomes.

PMID- 20146113
TI  - Inhibitors and facilitators of willingness to participate (WTP) in an HIV vaccine
      trial: construction and initial validation of the Inhibitors and Facilitators of
      Willingness to Participate Scale (WPS) among women at risk for HIV infection.
AB  - A psychometric scale assessing inhibitors and facilitators of willingness to
      participate (WTP) in an HIV vaccine trial has not yet been developed. This study
      aimed to construct and derive the exploratory factor structure of such a scale.
      The 35-item Inhibitors and Facilitators of Willingness to Participate Scale (WPS)
      was developed and administered to a convenience sample of 264 Black females
      between the ages of 16 and 49 years living in an urban-informal settlement near
      Cape Town. The subscales of the WPS demonstrated good internal consistency with
      Cronbach's alpha coefficients ranging between 0.69 and 0.82. A principal
      components exploratory factor analysis revealed the presence of five latent
      factors. The factors, which accounted for 45.93% of the variance in WTP, were (1)
      personal costs, (2) safety and convenience, (3) stigmatisation, (4) personal
      gains and (5) social approval and trust. Against the backdrop of the study
      limitations, these results provide initial support for the reliability and
      construct validity of the WPS among the most eligible trial participants in the
      Western Cape of South Africa.

PMID- 20146112
TI  - Psychosocial factors and substance use in high-risk youth living with HIV: a
      multi-site study.
AB  - The purpose of the study was to test relationships between psychosocial factors
      and alcohol and illicit drug use among high-risk youth living with HIV (YLH). One
      hundred eighty-six high-risk youth with HIV (defined as those with a substance
      use problem, sexual risk problem, or medication adherence problem) were enrolled
      across five cities (ages 16-24). Alcohol and illicit drug use were measured with
      the alcohol, smoking, and substance involvement screening test and a timeline
      follow-back interview. Questionnaires assessed constructs from the adapted
      Transtheoretical Model (TTM) including a continuous measure of motivational
      readiness in response to criticisms of the stage component. Path analysis was
      utilized to fit cross-sectional data collected via computer assisted personal
      interviewing (baseline data from intervention study). Separate models were fit
      for each commonly used substance. In the previous month, 47% used alcohol, 37%
      used cannabis, and 9% used other illicit drugs. Path models fit the data well and
      accounted for 30% of the variance in alcohol use and 47% in cannabis use. Higher
      self-efficacy predicted lower alcohol and cannabis use, but motivational
      readiness was only directly related to cannabis use. A reduction in pros of
      substance use was indirectly related to use. Social support and psychological
      distress were associated with TTM constructs. Interventions focusing on improving
      motivation and self-efficacy for healthy behaviors may reduce substance use in
      YLH.

PMID- 20146114
TI  - Special section: advances in the research of social anxiety and its disorder.

PMID- 20146115
TI  - Effect of affect on social cost bias in social anxiety disorder.
AB  - The cognitive model of social anxiety disorder (SAD) assumes that cognitive
      biases are important maintaining factors of the disorder. Research and theory
      have highlighted the impact of cognitive self-regulatory processes on affect, but
      have not sufficiently focused on the influence of affect on self-regulatory
      cognitions. The present study examined the influence of affect on cognitive self
      regulatory mechanisms in SAD by focusing on one critical cognitive bias,
      estimated social cost. Individuals with SAD (N=48) and non-anxious controls
      (N=48) were randomly assigned to one of three experimental, affect induction
      conditions (negative, positive, or neutral) before giving a 10-minute impromptu,
      videotaped speech. As expected, the affect manipulation resulted in changes in
      estimated social cost. However, this effect was not specific to individuals with
      SAD. Participants in the positive affect condition in both groups had the highest
      social cost estimates post-speech challenge. These results suggest that social
      cost bias is dependent on the affective state in both individuals with SAD and
      controls.

PMID- 20146116
TI  - An examination of the base rates of post-concussion symptoms: the influence of
      demographics and depression.
AB  - Post-concussion syndrome (PCS) is a controversial constellation of cognitive,
      emotional, and physical symptoms that some patients experience following a mild
      traumatic brain injury or concussion. PCS-like symptoms are commonly found in
      individuals with depression, pain, and stress, as well as healthy individuals.
      This study investigated the base rate of PCS symptoms in a healthy sample of 96
      participants and examined the relationship between these symptoms, depression,
      and sample demographics. PCS symptoms were assessed using the British-Columbia
      Post-Concussion Symptom Inventory. Depression was measured using the Beck
      Depression Inventory II. Results demonstrated that: The base rate of PCS was very
      high; there was a strong positive relationship between depression and PCS; and
      demographic characteristics were not related to PCS in this sample. These
      findings are broadly consistent with literature suggesting a significant role for
      non-neurological factors in the expression of PCS symptomatology. This study adds
      to the growing body of literature that calls for caution in the clinical
      interpretation of results from PCS symptom inventories.

PMID- 20146117
TI  - Factor analysis of the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS) in a large sample of patients suspected of
      dementia.
AB  - The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS;
      Randolph, 1998) is a popular neuropsychological assessment instrument with
      research supporting its clinical utility. However, the index structure of the
      RBANS was derived theoretically and was not based on factor analysis. The purpose
      of this study was to examine the factor structure in a large heterogeneous sample
      of patients referred for a dementia evaluation, using exploratory factor
      analysis. Results suggest a two-factor solution, the first factor defined
      predominantly as a memory factor and the second as predominantly a visuospatial
      factor. This study also sought to validate the obtained factors by examining
      their relationship with external neuropsychological variables. Correlations
      between the external variables provide further support for Factor 1 as a memory
      factor. Correlations with Factor 2 support its visuospatial features, although
      this factor may also be associated with other cognitive domains such as attention
      and general ability.

PMID- 20146118
TI  - Fostering adjustment to acquired brain injury by psychotherapeutic interventions:
      a preliminary study.
AB  - This preliminary study investigates the effectiveness of a treatment program in
      which neuropsychological interventions are supplemented by psychotherapeutic
      interventions to foster the adjustment process. Eleven patients who had an
      adjustment disorder following an acquired brain injury were recruited for the
      treatment group. Measures were assessed at the beginning and end using the
      Structured Clinical Interview, the Beck Depression Inventory, the Goal Attainment
      Scaling procedure, and the Trier Coping Scales. Significant pre- to post
      assessment differences emerged in terms of depression and coping styles. The
      findings suggest that patients benefit from an integrated treatment program to
      foster adjustment. These findings encourage further investigation of this
      integrative treatment in larger samples through randomized controlled trials with
      adequate control treatments.

PMID- 20146119
TI  - Reliability and validity of the Neuropsychological Assessment Battery-Screening
      Module (NAB-SM) in a sample of patients with moderate-to-severe acquired brain
      injury.
AB  - The Screening module from the Neuropsychological Assessment Battery (NAB-SM;
      Stern & White, 2003) is a comprehensive cognitive screening measure that assesses
      five domains (Attention, Language, Memory, Spatial, and Executive Functions). The
      construct validity of the NAB-SM in comparison to established neuropsychological
      (NP) measures in individuals with moderate-to-severe brain injury has yet to be
      investigated. Participants were 42 individuals with acquired brain injury
      admitted to a post-acute residential rehabilitation program. The NAB-SM cognitive
      domain index scores demonstrated weak internal consistency, whereas internal
      consistency for the NAB-SM total index score was satisfactory. In demonstrating
      construct validity, the NAB-SM cognitive domain index scores and individual
      subtest scores maintained several significant relationships with other NP tests
      that shared test structure and content or not. These relationships were limited
      or absent for the NAB-SM Executive Functions subtests and the NAB-SM Shape
      Learning subtest. Our findings provide preliminary support for the reliability
      and validity of the NAB-SM in a sample of patients with moderate-to-severe brain
      injury.

PMID- 20146120
TI  - Identifying cognitive problems in children and adolescents with depression using
      computerized neuropsychological testing.
AB  - Depression in children and adolescents can negatively impact cognitive
      functioning, social development, and academic performance. The purpose of this
      study was to determine whether a computerized battery of neuropsychological tests
      could detect neurocognitive difficulties in children and adolescents with
      depression. Participants included 30 children and adolescents between the ages of
      9 and 17 years (M = 14.6, SD = 2.1) with a clinical diagnosis of depression.
      Healthy control participants were individually matched on age, education, sex,
      race, primary language, handedness, and self-reported computer familiarity. All
      participants completed the Central Nervous System Vital Signs computerized
      battery. This battery of seven tests yields 23 test scores and 5 domain scores
      (Memory, Psychomotor Speed, Reaction Time, Complex Attention, and Cognitive
      Flexibility). Children and adolescents with depression performed worse on the
      Memory (Cohen's d = .43) and Complex Attention domains (d = .58) than matched
      controls. On the individual test scores, children and adolescents with depression
      performed worse on delayed verbal memory (d = .63), delayed visual memory (d =
      .34), measures of reaction time (d = .34-.53), and accuracy/inhibition on complex
      attention tasks (d = .49-.65). When considering the five domain scores
      simultaneously, children and adolescents with depression were more likely to have
      two or more scores at or below the 5th percentile (p = .05). Children and
      adolescents with depression have problems with reduced processing speed, memory
      for verbal information, and executive functioning on this computerized battery of
      tests, which represents a feasible method for neuropsychological screening.

PMID- 20146121
TI  - The relationship between adult neuropsychological profiles and diabetic patients'
      glycemic control.
AB  - The purpose of this study was to assess, in relation to metabolic control, the
      cognitive, depressive, and anxiety symptoms among 40 adult patients (age: 18-60
      years) with either type 1 (n = 28) or type 2 (n = 12) diabetes mellitus (DM1,
      DM2). Nineteen healthy subjects matched for age, gender, and education served as
      the control group. For most cognitive domains, no significant performance
      differences were found between subjects from the diabetic groups and control
      subjects. However, diabetes patients demonstrated reduced information processing
      accuracy along with impaired visual and verbal working memory performance. In
      addition, psychopathology scores were significantly elevated but did not reach
      the clinical criteria for depression or anxiety. Overall, there were no
      significant differences between diabetic subgroups, and no significant
      correlation was found between cognitive performance, psychopathology scores, and
      HbA1c values for either subgroup. Thus, patients with DM1 or DM2 may show mild-to
      moderate cognitive impairment as well as subtle psychopathological symptoms.
      While cognitive impairments may be understood in terms of diabetes-associated
      cognitive dysfunction, psychopathological symptoms may also result from
      unsuccessful coping with high task demands in everyday life activities. The
      outcome of the current study underscores the importance of early clinical
      neuropsychological standardized assessment as well as the diagnosis of cognitive
      and psychopathological symptoms in adult patients with diabetes.

PMID- 20146122
TI  - Symptom validity test performance in U.S. veterans referred for evaluation of
      mild TBI.
AB  - The current study examined Medical Symptom Validity Test (MSVT) performance in
      U.S. veterans referred for evaluation of mild traumatic brain injury (TBI) after
      scoring positive on the Veterans Health Administration (VHA) TBI screening
      measures. Fifty-eight percent of the sample scored below the MSVT cut scores on
      subtests more sensitive to effort than to neurological insult. There were no
      differences among those who did and those who did not pass the MSVT as a function
      of gender, age, education, ethnicity, previous posttraumatic stress disorder or
      substance use disorder diagnoses, or Personality Assessment Inventory validity
      scales designed to measure negative impression management. A higher number of
      those who were service connected and previously diagnosed with a depressive
      condition failed the measure at a higher rate than those who were not. These
      results are discussed in relation to the specific nature of VHA patient
      populations.

PMID- 20146123
TI  - The 'obsolescence' of assessment procedures.
AB  - The concept that obsolescence or being "out of date" makes a test or procedure
      invalid ("inaccurate," "inappropriate," "not useful," "creating wrong
      interpretations," etc.) has been widely accepted in psychology and
      neuropsychology. Such obsolescence, produced by publishing a new version of a
      test, has produced an extensive nullification of research effort (probably 10,000
      Wechsler studies). The arguments, attempting to justify obsolescence, include the
      Flynn Effect, the creation of a new version of a test or simply time. However,
      the Flynn Effect appears to have plateaued. In psychometric theory, validated
      tests do not lose their validity due to the creation of newer versions. Time does
      not invalidate tests due to the improvement of neurological methodology, such as
      magnetic resonance imaging. This assumption is unscientific, unproven, and if
      true, would discredit all older neuropsychological and neurological knowledge. In
      science, no method, theory, or information, once validated, loses that validation
      merely due to time or the creation of another test or procedure. Once validated,
      a procedure is only disproved or replaced by means of new research.

PMID- 20146124
TI  - Stability of the WISC-IV in a sample of elementary and middle school children.
AB  - This study investigated test-retest stability of the Wechsler Intelligence Scale
      for Children, Fourth Edition, in 43 elementary/middle school students tested on
      two occasions approximately 11 months apart. Subtest stability coefficients
      ranged from .26 (Picture Concepts) to .84 (Vocabulary [VC]). Composite
      stabilities ranged from .54 (Processing Speed Index) to .88 (Full Scale
      Intelligence Quotient [FSIQ]). On 11 subtests and three indexes, the
      standardization sample stability coefficients were significantly larger than
      those of the present sample, with only the VC subtest and FSIQ having high levels
      of test-retest stability. Mean practice effects were not significant, but range
      of gain or loss for some individuals was large. On the FSIQ, 42% changed > +/-5
      points on retest. The FSIQ is less stable than one might infer from the large
      stability coefficient and small mean practice effect.

PMID- 20146125
TI  - A single case report of Moyamoya disease presenting in a psychiatric setting.
AB  - Moyamoya disease (MMD) is a rare cerebral vasculopathy with limited information
      on the associated cognitive and emotional sequelae, particularly presenting in a
      psychiatric setting. We present the case of a 25-year-old female with a history
      of MMD and depressive disorder. She underwent revascularization surgery following
      an ischemic stroke at age 15 years. Magnetic resonance imaging at the time of the
      current assessment revealed markedly abnormal appearance in the anterior cerebral
      circulation with extensive periventricular collateral vasculature involvement.
      Neuropsychological assessment data revealed deficits in inhibition and problem
      solving, consistent with frontal lobe dysfunction. We discuss the importance of
      further research on the neuropsychological sequelae of MMD.

PMID- 20146127
TI  - Different sides of the same coin? Intercorrelations of cognitive biases in
      schizophrenia.
AB  - INTRODUCTION: A number of cognitive biases have been associated with delusions in
      schizophrenia. It is yet unresolved whether these biases are independent or
      represent different sides of the same coin. METHODS: A total of 56 patients with
      schizophrenia underwent a comprehensive cognitive battery encompassing paradigms
      tapping cognitive biases with special relevance to schizophrenia (e.g., jumping
      to conclusions, bias against disconfirmatory evidence), motivational factors
      (self-esteem and need for closure), and neuropsychological parameters.
      Psychopathology was assessed using the Positive and Negative Syndrome Scale
      (PANSS). RESULTS: Core parameters of the cognitive bias instruments were
      submitted to a principal component analysis which yielded four independent
      components: jumping to conclusions, personalising attributional style,
      inflexibility, and low self-esteem. CONCLUSIONS: The study lends tentative
      support for the claim that candidate cognitive mechanisms for delusions only
      partially overlap, and thus encourage current approaches to target these biases
      independently via (meta)cognitive training.

PMID- 20146128
TI  - An adaptive neurofuzzy technique for determination of blood acidity.
AB  - This paper presents an adaptive neurofuzzy-based method for the determination of
      blood acidity (pH). The main advantage of this method in comparison with
      conventional ones used for blood pH measurements is that it is capable of
      estimating the blood pH without the need for a pH sensor, which in turn reduces
      the volume of blood sample required to conduct the chemical analysis. This method
      uses blood carbon dioxide partial pressure (pCO2) and bicarbonate (HCO-3) as
      input to a neurofuzzy approach to predict the value of blood pH. This method was
      validated using 60 test data points that had not been used during the training
      process. The obtained results showed that the pH values predicted using this
      method have good concordance with experimentally measured pH values. The high
      correlation coefficient (87.6%) between the measured and the predicted pH values
      reflects the method's ability to measure (estimate) the pH values using pCO2 and
      HCO-3 with accuracy satisfying clinical demands.

PMID- 20146129
TI  - Human hand descriptions and gesture recognition for object manipulation.
AB  - This work focuses on obtaining realistic human hand models that are suitable for
      manipulation tasks. A 24 degrees of freedom (DoF) kinematic model of the human
      hand is defined. The model reasonably satisfies realism requirements in
      simulation and movement. To achieve realism, intra- and inter-finger constraints
      are obtained. The design of the hand model with 24 DoF is based upon a
      morphological, physiological and anatomical study of the human hand. The model is
      used to develop a gesture recognition procedure that uses principal components
      analysis (PCA) and discriminant functions. Two simplified hand descriptions (nine
      and six DoF) have been developed in accordance with the constraints obtained
      previously. The accuracy of the simplified models is almost 5% for the nine DoF
      hand description and 10% for the six DoF hand description. Finally, some criteria
      are defined by which to select the hand description best suited to the features
      of the manipulation task.

PMID- 20146130
TI  - Cluster analysis of pressure pain threshold maps from the trapezius muscle.
AB  - The aim of this study was to investigate and present a new mapping method to
      describe muscle pain sensitivity based on the assessment of pressure pain
      threshold (PPT) over the trapezius muscle. PPT data were recorded from 36 points
      in 20 healthy males using a standardised grid. Points were clustered using the K
      means algorithm with a fixed initialisation procedure. The total number of
      clusters was determined on the basis of (1) R(2) evaluation of the clustering
      outcome compared against a desired 95% reduction in variance criterion and (2)
      the number of empty clusters. A minimum of three clusters were found which
      fulfilled the criteria. The proposed method enables the identification of a
      relation between the muscle subdivisions and pressure pain sensitivity within the
      trapezius. Further, the cluster analysis will enable the study of differences in
      pain sensitivity distributions between patients and controls and quantify the
      effect of intervention (physical or pharmacological treatments).

PMID- 20146131
TI  - Prediction of nonlinear elastic behaviour of vaginal tissue: experimental results
      and model formulation.
AB  - The mechanical properties of the vaginal tissue need to be characterised to
      perform accurate simulations of prolapse and other pelvic disorders that commonly
      affect women. This is also a fundamental step towards the improvement of
      therapeutic techniques such as surgery. Issues like the efficiency of using
      autologous tissue in pelvic reconstruction may be addressed. The goal of this
      study was to characterise the elastic behaviour of vaginal tissue. For this
      purpose, prolapsed vaginal tissue from eight different post-menopausal patients,
      excised during prolapse corrective surgery, was mechanically tested. The
      mechanical testing of vaginal tissue, consisting of uniaxial tension tests
      performed along the longitudinal axis of the vagina, revealed the nonlinear
      mechanical behaviour of the tissue. The material model parameters were fit to the
      experimental data using the Levenberg-Marquardt optimisation algorithm. All the
      curve fittings showed a good agreement between experimental and theoretical
      results, evidenced by R2 values close to 1 and by very low epsilon values.

PMID- 20146134
TI  - Stoffenmanager exposure model: company-specific exposure assessments using a
      Bayesian methodology.
AB  - The web-based tool "Stoffenmanager" was initially developed to assist small- and
      medium-sized enterprises in the Netherlands to make qualitative risk assessments
      and to provide advice on control at the workplace. The tool uses a mechanistic
      model to arrive at a "Stoffenmanager score" for exposure. In a recent study it
      was shown that variability in exposure measurements given a certain
      Stoffenmanager score is still substantial. This article discusses an extension to
      the tool that uses a Bayesian methodology for quantitative workplace/scenario
      specific exposure assessment. This methodology allows for real exposure data
      observed in the company of interest to be combined with the prior estimate (based
      on the Stoffenmanager model). The output of the tool is a company-specific
      assessment of exposure levels for a scenario for which data is available. The
      Bayesian approach provides a transparent way of synthesizing different types of
      information and is especially preferred in situations where available data is
      sparse, as is often the case in small- and medium sized-enterprises. Real-world
      examples as well as simulation studies were used to assess how different
      parameters such as sample size, difference between prior and data, uncertainty in
      prior, and variance in the data affect the eventual posterior distribution of a
      Bayesian exposure assessment.

PMID- 20146135
TI  - The assessment and rehabilitation of prospective memory problems in people with
      neurological disorders: a review.
AB  - People with neurological disorders often report difficulty with prospective
      memory (PM), that is, remembering to do things they had intended to do. This
      paper briefly reviews the literature regarding the neuropsychology of PM
      function, concluding that from the clinical perspective, PM is best considered in
      terms of its separable but interacting mnemonic and executive components. Next,
      the strengths and limitations in the current clinical assessment of PM, including
      the assessment of component processes, desktop analogues of PM tasks, and
      naturalistic PM tasks, are outlined. The evidence base for the rehabilitation of
      PM is then considered, focusing on retraining PM, using retrospective memory
      strategies, problem-solving training, and finally, electronic memory aids. It is
      proposed that further research should focus on establishing the predictive
      validity of PM assessment, and refining promising rehabilitation techniques.

PMID- 20146136
TI  - Rehabilitation of divided attention after severe traumatic brain injury: a
      randomised trial.
AB  - Patients with severe traumatic brain injury (TBI) frequently suffer from a
      difficulty in dealing with two tasks simultaneously. However, there has been
      little research on the rehabilitation of divided attention. The objective of the
      present study was to assess the effectiveness of a rehabilitation programme for
      divided attention after severe TBI. Twelve patients at a subacute/chronic stage
      after a severe TBI were included. A randomised AB vs. BA cross-over design was
      used. Training lasted six weeks, with four one-hour sessions per week. It was
      compared to a non-specific (control) cognitive training. During experimental
      treatment, patients were trained to perform two concurrent tasks simultaneously.
      Each one of the two tasks was first trained as a single task, then both tasks
      were given simultaneously. A progressive hierarchical order of difficulty was
      used, by progressively increasing task difficulty following each patient's
      individual improvement. Patients were randomised in two groups: one starting with
      dual-task training, the other with control training. Outcome measures included
      target dual-task measures, executive and working memory tasks, non-target tasks,
      and the Rating Scale of Attentional Behaviour addressing attentional problems in
      everyday life. Assessment was not blind to treatment condition. A significant
      training-related effect was found on dual-task measures and on the divided
      attention item of the Rating Scale of Attentional Behaviour. There was only
      little effect on executive measures, and no significant effect on non-target
      measures. These results suggest that training had specific effects on divided
      attention and helped patients to deal more rapidly and more accurately with dual
      task situations.

PMID- 20146137
TI  - Evaluation of New Jersey's graduated driver licensing program.
AB  - OBJECTIVE: The objective of this study was to evaluate New Jersey's unique
      combination of a higher licensing age and a strong GDL system applicable to all
      novice drivers. METHODS: Population-based crash rates for drivers of ages
      potentially affected by GDL were compared, pre- and post-GDL implementation, with
      those of adults ages 25-59, using data on fatal crashes and on all police
      reported crashes. RESULTS: After GDL implementation, there were statistically
      significant reductions in the crash rates of 17-year-olds, based on all reported
      crashes (16%), injury crashes (14%), and fatal crashes (25%), relative to those
      of drivers ages 25-59. The crash rates of 18-year-olds decreased significantly on
      the basis of all reported crashes (10%) and injury crashes (10%), relative to
      those of drivers ages 25-59. The fatal crash involvement rate of 18-year-olds
      decreased by 4 percent, which was not statistically significant. There was also a
      statistically significant reduction in fatal crashes of 16-year-old drivers;
      however, this is unlikely to have been attributable to GDL. Significant
      reductions in nighttime crashes (of all severity levels) of drivers ages 17 and
      18 were observed, as were significant yet smaller reductions in their daytime
      crash rates. Reductions in fatal crashes of 17- and 18-year-olds carrying more
      than one passenger were sizable (23 and 24%, respectively) but were not
      statistically significant. CONCLUSIONS: New Jersey's licensing age of 17
      eliminates most crashes at age 16. To the extent that the relative inexperience
      of 17-year-old drivers may negatively impact their crash rates, this effect
      appears to be largely blunted by New Jersey's strong GDL system. New Jersey's GDL
      system also reduces crashes at age 18, an age group untouched by other states'
      GDL systems. New Jersey's combination of licensing policies for young drivers is
      a model for the nation.

PMID- 20146138
TI  - Road crash trends for young drivers in New South Wales, Australia, from 1997 to
      2007.
AB  - OBJECTIVES: The objective of this article was to explore overall crash and injury
      trends over the past decade for young drivers residing in New South Wales (NSW),
      Australia, including gender and age disparities. METHODS: Passenger vehicle
      crashes for drivers aged 17-25 occurring during 1997-2007 were extracted from the
      state crash database to calculate crash rates (per licensed driver). Generalized
      linear models were used to examine crash trends over time by severity of driver
      injury, adjusting for age, gender, rurality of residence, and socioeconomic
      status. Yearly adjusted relative risks of crash by gender and by age group were
      also examined over the study period. RESULTS: Young driver noninjury and fatality
      rates significantly decreased by an average of 4 percent (95% CI: 4-5) and 5
      percent (95% CI: 0-9) respectively each year from 1997 to 2007. Young driver
      injury rates significantly increased by about 12 percent (95% CI: 9-14) to the
      year 2001 and then significantly decreased. The relative risk of crash
      (regardless of driver injury) for males compared to females significantly
      decreased over time. Compared to drivers aged 21-25, drivers aged 17 and
      particularly 18- to 20-year-olds had significantly and consistently higher crash
      risks across the study period. CONCLUSIONS: Overall, there has been a significant
      decline in young driver crashes in NSW over the last decade. Regardless of injury
      severity, males' risk of crash has reduced more than female young drivers, but
      drivers aged 17 continue to be at higher risk. These findings provide feedback on
      potential road safety successes and areas needing specific interventions for
      future improvements.

PMID- 20146139
TI  - Effects of a simulation-based training intervention on novice drivers' hazard
      handling performance.
AB  - OBJECTIVES: Young novice drivers are overrepresented in crash rates during their
      first few months of driving. The dramatic drop afterwards implies that some
      important skills of safe driving are learned during this period. In an attempt to
      help novice drivers acquire higher-order perceptual and cognitive skills for safe
      driving, a training intervention based on driving simulation was developed,
      tested, and evaluated. METHODS: Eight virtual driving scenarios (four equivalent
      and four analogical) were developed for road hazard handling training, and
      another eight scenarios were developed for subsequent formal testing. Two groups
      of novice drivers were recruited to test and compare their road hazard handling
      performance. The trained group received training treatment 6 weeks before
      testing, whereas the untrained group had no prior training except a basic driving
      skill exercise. The comprehensive training intervention included simulated
      driving in eight virtual scenarios, then feedback of their own hazard handling
      performance, and finally watching the playback video of an experienced driver's
      handling of each road hazard. RESULTS: Road hazard handling performance scores
      were significantly higher for the trained group and the training effect was
      greater for equivalent scenarios than for analogical ones. The trained drivers
      anticipated potential hazards in advance to a larger extent than the untrained,
      as indicated by both earlier speed reduction and subjective self-report data when
      approaching the hazards. Subjective mental workload of the trained drivers was
      significantly lower in completing the simulated driving task. CONCLUSIONS: The
      tested comprehensive training intervention has shown positive effects in
      improving novice drivers' abilities to anticipate, recognize, and deal with
      hazards in simulated driving. Performance of the trained drivers with different
      starting levels converged to a relatively high level after training.

PMID- 20146141
TI  - Proportion of injured drivers presenting to a tertiary care emergency department
      who engage in future impaired driving activities.
AB  - OBJECTIVE: We determined the rate of, and predictive factors for, subsequent
      impaired driving activity (IDA) by injured drivers treated in a Canadian tertiary
      care emergency department (ED) following a motor vehicle crash (MVC). METHODS: We
      retrospectively identified all drivers injured in a MVC who presented to our
      tertiary care, urban ED (1999-2003) and had their blood alcohol content (BAC)
      measured. Injured drivers were categorized by BAC: group 1, BAC = 0; group 2, 0 <
      BAC < or = 17.3 mM (80 mg/dL, legal limit); and group 3, BAC > 17.3 mM. IDA was
      defined as any of the following: a conviction for impaired driving; a 24-h or 90
      day license suspension for impaired driving; involvement in alcohol-related MVC.
      Time to IDA following the index event between groups was compared with Kaplan
      Meier survival analyses. Effects of covariates on time to IDA were analyzed using
      Cox proportional hazards models. RESULTS: During the study period, 1489 injured
      drivers met study criteria: 1171 in group 1, 51 in group 2, and 267 in group 3.
      During an average follow-up of 52.4 months, 82 (30.7%) group 3 drivers engaged in
      subsequent IDA, compared with 80 (6.8%) group 1 drivers (p < 0.0001). Youth, male
      gender, history of previous IDA, and the number of previous IDA events were all
      associated with a significant increase in subsequent IDA. A history of IDA was
      the strongest predictor of future IDA in group 1 (440% increase risk) and in
      group 3 (80% increased risk). The magnitude of BAC elevation above the legal
      limit was not predictive of future IDA. CONCLUSIONS: A high portion of injured
      impaired drivers who present to hospital engage in repeat IDA following
      discharge. Besides impairment at time of hospital visit, the best predictor of
      future IDA is a history of IDA prior to the index event.

PMID- 20146140
TI  - Risk-taking behaviors among motorcyclists in middle east countries: a case of
      islamic republic of Iran.
AB  - OBJECTIVE: Injuries caused by motor vehicle crashes in Middle Eastern countries
      are among the highest in the world. In Iran, road traffic crashes are the second
      most common cause of mortality. Particularly, motorcycle-related injuries among
      men are the second most common type of traffic-related crash in this country.
      This study used qualitative research methods to elicit and explore the personal
      experiences of Iranian motorcyclists in respect to factors that facilitate their
      engagement in risk-taking behaviors within the PRECEDE (predisposing,
      reinforcing, and enabling constructs in educational diagnosis, and evaluation)
      framework. METHODS: Focus groups, in-depth interviews, and field observation were
      conducted among motorcyclists, pillion passengers, and police officers. RESULTS:
      Our data show that being young and single, living in lower socioeconomic
      conditions, and suffering from poor physical health and daily stress influence
      risk-taking behaviors. Additionally, lack of defined traffic rules and
      regulations, the availability and accessibility of motorcycles among unlicensed
      underaged persons, the cost-effectiveness of motorcycle transportation, unsafe
      roads and a lack of special pathways for motorcycles, and aggressive car and
      van/truck drivers are among the enabling factors that provoke risk-taking
      behavior. Finally, the participants verified that the enjoyment of motorcycling
      reinforced their decision to continue engaging in risky behaviors, and being
      penalized for disobeying traffic laws prevented them from further risk-taking
      behaviors. CONCLUSION: Enabling and reinforcing factors to reduce risk-taking
      behaviors among motorcyclist could include (1) promoting smart driving practices
      among motorcyclists; (2) training pediatricians and emergency physicians to
      deliver brief motivational interventions to their young patients to avoid risky
      behaviors while riding; (3) training traffic enforcement officers to appreciate
      the value of providing consistent law enforcement services; (4) enhancing local
      efforts to increase the number of pathways for motorcyclists and improve the
      condition of deteriorated roads; (5) revising legislation and policies in
      association with motorcycle ownership among underaged and unlicensed individuals;
      (6) limiting an excessive number of passengers (particularly children) and cargo
      on motorcycles; and (7) identifying solutions to reduce the negative attitudes of
      car drivers toward motorcyclists and increase systematic compliance of traffic
      laws by motorcyclists and car drivers.

PMID- 20146142
TI  - Motor vehicle and pedestrian collisions: burden of severe injury on major versus
      neighborhood roads.
AB  - OBJECTIVE: To determine whether the severity of injuries sustained by pedestrians
      involved in motor vehicle collisions varies by road type and age. METHODS: All
      police-reported pedestrian motor vehicle collisions in the city of Toronto,
      Canada, between January 1, 2000, and December 31, 2005, were analyzed. Geographic
      Information Systems software was used to determine whether the collisions
      occurred on major or neighborhood roads. Age-specific estimates of the burden of
      pedestrian collisions are presented. Odds ratios and 95 percent confidence
      intervals were calculated to examine age-specific relationships between injury
      severity and road type. A second analysis comparing the distribution of severe
      injury location between age groups was also performed. RESULTS: The majority of
      collisions involved adults (68%), although elderly pedestrians were
      overrepresented in fatal collisions (49%). Severe and fatal collisions involving
      working-age and elderly adult pedestrians were more likely on major roads. Odds
      of severe injury occurring on a major road were 1.36 (95% CI: 1.17-1.57) times
      higher for adults ages 18 to 64, and 1.55 (95% CI: 1.22-1.99) times higher for
      elderly aged 65+. By contrast, severe injuries among children were more common on
      neighborhood roads, with odds of severe injury on a major road of 0.64 (95% CI:
      0.37-1.1) for children aged 5 to 9. Among children under 9, 64-67 percent of
      hospitalized or fatal injuries occurred on neighborhood roads, a marked
      difference from the distribution of such injuries in adults or the elderly, for
      whom only 29-30 percent of hospitalized or fatal injuries occurred on
      neighborhood roads (chi-square = 52.6, p < or =.001). CONCLUSIONS: Targeting
      interventions toward the adult pedestrian burden on major roads alone will not
      make child pedestrians safer. Pedestrian interventions specific to children and
      focused on neighborhood roads must be considered in urban centers like Toronto.

PMID- 20146143
TI  - Do light truck vehicles (LTV) impose greater risk of pedestrian injury than
      passenger cars? A meta-analysis and systematic review.
AB  - OBJECTIVE: Pedestrian crashes present a growing challenge for public health
      trauma and road safety researchers around the world. They are associated with
      substantial morbidity, mortality, and cost, yet there is an international lack of
      published work on the topic, especially when compared with vehicle occupant
      safety studies. Our review attempts to quantify the risk of fatal injury among
      vulnerable road users. The specific objective of this systematic review and meta
      analysis is to quantify and compare the impact of light truck vehicles (LTVs)
      versus conventional cars on pedestrian fatal injury. METHODS: A protocol was
      developed using methods of the Cochrane Collaboration. We conducted a search for
      the studies in bibliographic databases that included ATI (Australian Transport
      Index); Cochrane Injuries Group Specialized Register; EMBASE; ERIC; MEDLINE;
      National Research Register; PsycINFO; Road Res (ARRB); SIGLE; Science (and Social
      Science) Citation Index; TRANSPORT (NTIS, TRIS, TRANSDOC, IRRD). Web sites of
      traffic and road accident research bodies, government agencies, and injury
      prevention organizations were searched for grey literature. Reference lists from
      selected papers or topic reviews were scanned for potentially relevant papers.
      RESULTS: Our initial search identified 878 potentially eligible studies. After
      thorough review by three of the researchers a total of 12 studies were included
      in the systematic review, 11 of which were included in the meta-analysis. The
      overall pooled odds ratio for the risk of fatal injury in pedestrian collisions
      with LTVs compared to conventional cars was odds ratio 1.54, 95 percent
      confidence interval 1.15-1.93, p = 0.001. Thus, the risk for pedestrians of
      sustaining fatal injury is 50 percent greater in collisions with LTVs than in
      collisions with conventional cars. CONCLUSIONS: Our systematic review and meta
      analysis suggests that LTVs pose a greater risk of pedestrian injury death
      compared to conventional cars. These findings have important implications for the
      automotive industry and the safety of vulnerable road users.

PMID- 20146144
TI  - Addressing pedestrian safety: a content analysis of pedestrian master plans in
      North Carolina.
AB  - OBJECTIVE: To systematically examine the content of pedestrian master plans in
      North Carolina in order to assess whether and how these plans were designed to
      improve pedestrian safety. METHODS: All current pedestrian master plans in North
      Carolina through 2008 were gathered and examined using content analysis. A safety
      quality index was developed to assess the thoroughness with which a plan
      addressed safety issues in four categories: (1) goal statement, (2) analysis of
      current conditions, (3) policy proposals, and (4) program proposals. Plans were
      also compared according to the implementation guidelines included and on the
      recent pedestrian accident history of the municipalities in which they were
      developed. RESULTS: Forty-six plans were developed in North Carolina through
      2008, either at the municipal or regional level. Almost all pedestrian master
      plans in North Carolina described improving safety as one of their goals. The
      majority attempted to do so by improving the built environment through
      engineering projects, including building new sidewalks, trails, or greenways and
      by upgrading existing facilities. Regional plans tended to propose fewer policies
      and programs, as well as less specific proposals, than did municipal plans.
      Although most plans contained multiple proposals to address pedestrian safety,
      few plans identified a group accountable for implementation, a timeline of
      implementation actions, or the resources necessary to make implementation
      possible. Municipalities with a recent history of pedestrian injuries were more
      likely to develop plans than those with fewer pedestrian injuries. Plans
      developed by municipalities with a recent history of pedestrian fatalities tended
      to more thoroughly addressed safety. CONCLUSION: Safety was a major component of
      nearly every pedestrian master plan in North Carolina. Most plans contained
      multiple proposals to address pedestrian safety. These findings lay the
      foundation for future research evaluating both the implementation and the impact
      of these planning documents on the safety of pedestrians.

PMID- 20146145
TI  - Survival in fatal road crashes: body mass index, gender, and safety belt use.
AB  - BACKGROUND: This study evaluated the associations of body mass index (BMI),
      gender, and use of safety belts with the survival of drivers involved in fatal
      road crashes. METHOD: The census data of all U.S. fatal crashes that did not
      involve pedestrians, bicyclists, or motorcyclists were examined for an 11-year
      period. RESULTS: If involved in a crash with one or more fatalities, the odds of
      female drivers being among the fatalities are 1.28 times higher than those of
      male drivers, and the odds of unbelted drivers being among the fatalities are
      5.43 times higher than those of belted drivers. The relationship of survivability
      to BMI depends on the gender and safety belt use of the driver. CONCLUSIONS: For
      male drivers, increased BMI appears beneficial when safety belts are used but
      detrimental when not used. For belted female drivers, normal BMI is associated
      with the lowest odds of being killed, and both increased and decreased BMIs
      increase the odds. For unbelted female drivers, no reliable trends were present
      among the BMI categories.

PMID- 20146146
TI  - Severe injury to near- and far-seated occupants in side impacts by crash severity
      and belt use.
AB  - PURPOSE: This study investigated the risk of severe-to-fatal injury (MAIS 4+F) to
      near- and far-seated front occupants in side impacts by belt use and crash
      severity (delta V). METHODS: 1993-2007 NASS-CDS was analyzed for front-seat
      occupants in side impacts while they were either the near-side or far-side
      occupant by belt use. Light vehicles were included with model year 1994+. Injury
      severity was subdivided into MAIS 0-2, 3, and 4+F. The risk for MAIS 4+F injury
      was determined by dividing the number of MAIS 4+F by the number of exposed
      occupants with known injuries. Individual NASS-CDS cases were downloaded from the
      1997-2007 electronic data to evaluate injury patterns causing high relative
      risks. RESULTS: In 35+ mph side-impact delta Vs, the risk for MAIS 4+F injury was
      75.4 +/- 41.0% for unbelted near-side and 48.1 +/- 14.6% for unbelted far-side
      occupants. The risk was 51.8 +/- 14.8% for belted near-side and 30.9 +/- 8.2% for
      far-side occupants. Seat belt use was 81.4% effective in preventing MAIS 4+F
      injury for near-side occupants and 93.5% for far-side occupants. The relative
      risk (RR) for unbelted compared to belted occupants was 35.9 for far-side
      occupants in 10-15 mph delta V crashes. The relative risk was 35.1 for near-side
      occupants in < 10 mph delta V side impacts. The high relative risks were
      associated with complex, high-speed multi-collision crashes often with occupant
      impacts on the windshield, steering wheel, or other frontal components and
      ejection. CONCLUSIONS: Seat belt use was more effective in preventing severe
      injury (MAIS 4+F) to far-side occupants than near-side occupants in < 25 mph
      delta V impacts. High relative risk for unbelted occupants in low-speed side
      impacts was explained by the fact that the accidents were high-speed, multi
      impact collisions. Severe injury was caused by ejection, impact with the side
      interior, or impact with the frontal components where airbags sometimes deployed.

PMID- 20146147
TI  - Ejection and severe injury risks by crash type and belt use with a focus on rear
      impacts.
AB  - PURPOSE: This study investigated the risk of severe-to-fatal injury (MAIS 4+F)
      with complete and partial ejection by crash type and belt use with a focus on
      ejection in rear impacts. METHODS: 1993-2007 NASS-CDS was analyzed for crashes
      with complete and partial ejection. The effect of belt use was investigated and
      crashes were grouped by front, side, rear, and rollovers. Light vehicles were
      included with model year 1994+. Injuries of severity MAIS 4+F and AIS 3-6 by body
      region were determined by crash type, belt use, and ejection status. NASS-CDS
      electronic cases of complete ejection and serious injury were evaluated to
      determine the circumstances in rear impacts. RESULTS: For unbelted occupants, the
      highest risk for complete ejection is in rollovers (16.4 +/- 1.1%) and the risk
      for severe injury is 37.6 +/- 2.7%. The lowest risk for complete ejection is in
      frontal crashes (0.97 +/- 0.22%), but the risk for serious injury is 31.3 +/-
      6.2% when ejection occurs. The risk for ejection is 2.7 +/- 1.5% in rear impacts
      with a 7.4 +/- 3.4% risk for severe injury. For belted occupants, the highest
      risk for complete ejection is in rollovers (0.068 +/- 0.022%) and the risk for
      severe injury is 25.9 +/- 13.3% when ejection occurs. The relative risk for
      ejection is 193 times greater for unbelted compared to belted occupants in all
      crashes with a range of 100 times in frontal crashes up to 847 times in rear
      impacts. Unbelted occupants have 20 times greater risk for severe injury when
      completely ejected and 18 times greater risk with partial ejection compared to
      nonejected occupants. Belted occupants have a 77 times greater risk of severe
      injury when completely ejected and 37 times greater risk when partially ejected.
      CONCLUSIONS: Ejection involves significantly higher risks for severe injury in
      all crash types. The relative risk for MAIS 4+F injury is 20 times greater for
      unbelted and 77 times greater for belted occupants who are completely ejected
      compared to nonejected occupants. Ejection of occupants in rear crashes often
      occurs during vehicle yaw motion after the primary impact.

PMID- 20146148
TI  - With power comes responsibility: motorcycle engine power and power-to-weight
      ratio in relation to accident risk.
AB  - OBJECTIVE: Current European legislation allows the EU member states to restrict
      the maximum power output of motorcycles to 74 kW even though evidence supporting
      the limit is scarce and has produced mixed results-perhaps because motorcycle
      performance has been measured by engine displacement, not engine power, in most
      of the previous studies. This study investigates the relationship of motorcycle
      engine power and power-to-weight ratio to risk of fatal and nonfatal crashes in
      Finland. METHODS: The fatality rate (number of fatal accidents/number of
      registered motorbikes) for riders of different ages riding bikes belonging to
      different power and power-to-weight ratio classes was examined using a
      comprehensive in-depth database. Data on nonfatal accidents were acquired from a
      Web questionnaire (N = 2708), which also served as a basis for estimating riders'
      annual mileage. Mileage data allowed the calculation of accident risk per
      kilometer ridden for bikes differing in power and power-to-weight ratio. RESULTS:
      The fatality risk per number of registered motorcycles and per kilometer ridden
      increases both with power and power-to-weight ratio, independently of rider's
      age. No relationship between performance and risk of a less severe crash was
      found. The pre-accident speed of the most powerful bikes was 20 km/h or more over
      the speed limit in a large proportion of the fatal accidents (odds ratio = 4.8
      for > 75 kW motorbikes; odds ratio = 6.2 for > 0.3 kW/kg motorbikes). CONCLUSION:
      The risk of being involved in a fatal crash is higher among the riders of
      powerful motorcycles. However, it is not clear whether the results are related to
      the riding habits of the riders that choose the most powerful bikes available or
      whether the high risk is due to the properties of the bikes themselves.
      Therefore, further research is needed before considering legal limits on
      motorcycle performance.

PMID- 20146149
TI  - Assessing the role of pavement macrotexture in preventing crashes on highways.
AB  - OBJECTIVE: The objective of this article is to assess the role of pavement
      macrotexture in preventing crashes on highways in the State of North Carolina.
      METHODS: Laser profilometer data obtained from the North Carolina Department of
      Transportation (NCDOT) for highways comprising four corridors are processed to
      calculate pavement macrotexture at 100-m (approximately 330-ft) sections
      according to the American Society for Testing and Materials (ASTM) standards.
      Crash data collected over the same lengths of the corridors were integrated with
      the calculated pavement macrotexture for each section. Scatterplots were
      generated to assess the role of pavement macrotexture on crashes and logarithm of
      crashes. Regression analyses were conducted by considering predictor variables
      such as million vehicle miles of travel (as a function of traffic volume and
      length), the number of interchanges, the number of at-grade intersections, the
      number of grade-separated interchanges, and the number of bridges, culverts, and
      overhead signs along with pavement macrotexture to study the statistical
      significance of relationship between pavement macrotexture and crashes (both
      linear and log-linear) when compared to other predictor variables. RESULTS:
      Scatterplots and regression analysis conducted indicate a more statistically
      significant relationship between pavement macrotexture and logarithm of crashes
      than between pavement macrotexture and crashes. The coefficient for pavement
      macrotexture, in general, is negative, indicating that the number of crashes or
      logarithm of crashes decreases as it increases. The relation between pavement
      macrotexture and logarithm of crashes is generally stronger than between most
      other predictor variables and crashes or logarithm of crashes. CONCLUSIONS: Based
      on results obtained, it can be concluded that maintaining pavement macrotexture
      greater than or equal to 1.524 mm (0.06 in.) as a threshold limit would possibly
      reduce crashes and provide safe transportation to road users on highways.

PMID- 20146150
TI  - Evaluating the role of weaving section characteristics and traffic on crashes in
      weaving areas.
AB  - OBJECTIVE: The likelihood of being involved in a crash on a freeway, in general,
      is greater on weaving sections than on basic freeway sections and in ramp
      influence areas. This is due to possible crossing of entry and/or exit traffic
      over a short distance while traveling in the same direction without the aid of
      traffic control devices resulting in potential conflicting situations and
      crashes. This article focuses on evaluating the role of weaving section
      characteristics (configuration type, length and the number of required lane
      changes by weaving traffic) and traffic variables (entry volume, exit volume, and
      non-weaving volume) on crashes in weaving areas. METHODS: Data collected for 25
      weaving sections in the Las Vegas metropolitan area are used to study the
      relationship between crashes and weaving section characteristics and traffic
      variables. The relationship between (1) crashes by selected collision types and
      contributing factors and (2) weaving section characteristics and traffic
      variables are also examined. Descriptive and statistical analysis techniques were
      used. RESULTS: The number of crashes tends to decrease with increase in length of
      weaving section. Increase in entry volume increases crashes due to improper lane
      change and ran off roadway crashes. On the other hand, increase in exit volume
      increases rear-end crashes, crashes due to following too closely, and crashes due
      to inattentive driving. Non-weaving volume, in general, also appears to play a
      prominent role in explaining most crash types and contributing factors on weaving
      sections. CONCLUSIONS: Type "A" weaving section tends to be relatively safer when
      compared to other weaving configuration section types. Retrofitting weaving
      sections with short lengths or designing sections with longer lengths, in
      addition to increased use of in-vehicle warning systems, may reduce crashes and
      improve safety. Ramp metering, enforcement, changeable message signs (speed
      signs), and capacity improvements are other solutions for consideration.

PMID- 20146151
TI  - [Deep brain stimulation in neurology and psychiatry].

PMID- 20146152
TI  - [Dual diagnosis psychosis and substance use disorders in adolescents--part 1].
AB  - Epidemiological studies suggest that 20 % to 50 % of patients with schizophrenia
      have a lifetime comorbid substance use disorder (SUD). In first-episode psychosis
      this prevalence is even higher and varies between 20 % and 75 % with cannabis
      being the most widely used illicit drug. These difficult to treat patients
      usually have a worse prognosis as compared with non-substance abusing
      schizophrenic patients. Despite multiple theories proposed such as the self
      medication hypothesis, common or bidirectional factor models or genetic
      vulnerability, there is no consensus on the aetiology of increased rates of
      substance use in people with psychosis which is important to treat these
      patients. The dually diagnosed population is a heterogeneous group and it is
      likely that different models may explain comorbidity in different subgroups. The
      present review part one gives an overview on prevalence and explanation models
      for dual diagnosis psychosis and substance use with focus in adolescent and young
      adult populations, the second part reviews the clinical course for both disorders
      and current psychosocial treatment options.

PMID- 20146153
TI  - [Dual diagnosis psychosis and substance use disorders in adolescents--part 2].
AB  - Despite the high prevalence of comorbid substance use disorders (SUD) in young
      schizophrenic patients and the association of persisting SUD and poor outcome,
      there are only few randomized controlled psychological treatment studies in this
      special dual diagnosis group available. According to therapeutic recommendations,
      efficient treatment models need to integrate traditional psychiatric therapy and
      therapy of addiction offered in one setting. Short-term interventions have
      adapted Motivational interviewing (MI) for dual diagnosis, which has been shown
      to be effective among other substance abuse disorders. However a recent Cochrane
      review showed that insufficient evidence exists to show that any psychosocial
      treatment method for dual diagnosis is superior to others. The aim of this review
      was to assess the current evidence for the efficacy of psychosocial interventions
      for reducing substance in young patients with psychosis. Five randomized
      controlled studies were identified. This review did not find any specific
      psychosocial intervention that had been replicated and consistently showed clear
      advantages over comparison condition for substance-related and other psychiatric
      outcomes.

PMID- 20146154
TI  - [Wake up stroke: Overview on diagnostic and therapeutic options for ischemic
      stroke on awakening].
AB  - Up to 25 % of all acute ischemic strokes (AIS) occur during sleep with the
      patients or relatives becoming aware of their neurological deficits as they wake
      up. Because of the unclear time of stroke onset patients with stroke on awakening
      are usually not considered for acute therapies and excluded from most treatment
      trials. We give an overview of the published data regarding ischemic wake up
      strokes (WUS). In particular we focused on baseline characteristics, imaging
      methods and therapy strategies. Comparing WUS patients and patients with known
      stroke onset there were no major differences found regarding patient
      characteristics, etiology, clinical and radiological characteristics. Even though
      there is no existing gold standard multiparametric neuroimaging (CT; MRI) appears
      to be helpful for decision making whether to treat a WUS patient with
      thrombolysis or not. Especially multiparametric MRI which proved to be safe in
      patients within an extended time window might serve as an adequate diagnostic
      tool. The results of first pilot studies analyzing treatment of WUS demonstrate
      that a substantial number of these patients can be treated with IV thrombolysis
      (IVT) successfully. Large randomized, controlled, prospective clinical trials for
      patients with WUS are needed to test safety and efficacy of IVT and to evaluate
      the assumed benefit of multiparametric neuroimaging techniques in this patient
      group. The results of first pilot studies may be instrumental to help plan and
      design such trials.

PMID- 20146155
TI  - [Deep brain stimulation in neurology - indications and results].

PMID- 20146156
TI  - [Costs of ulcerative colitis within the German Statutory Health Insurance].
AB  - BACKGROUND AND OBJECTIVES: Studies estimating the costs of ulcerative colitis
      (UC) within the German setting are limited. The aim of this cross-sectional study
      was to collect data on the overall costs arising from the care of patients with
      UC and to quantify this expenditure as incurred by the German Statutory Health
      Insurance (SHI). METHODS: Between March 2006 and July 2007 patients from 24
      ambulatory gastroenterologist practices and two hospitals were enrolled in an
      internet-based database. Outpatient and inpatient visits, all procedures as well
      as drug usage were obtained from the collected data and evaluated from the
      perspective of the SHI, taking also into account statutory discounts and
      patients' co-payments. The year 2007 was selected as the pricing period. RESULTS:
      Data from 519 patients with UC were collected (gender ratio 1:1; average age 46
      years). The average annual cost per UC patient to the SHI is 2,477.72 Euro, 74 %
      of this amount results from drug usage, 10 % from inpatient care and another 10 %
      from ambulatory procedures. Costs increase with the severity of the disease.
      CONCLUSION: This is the first study to calculate the costs caused by UC and payed
      by the SHI in Germany. Future research should focus on collecting longitudinal
      data and also on comparing the resources used in the care of patients with other
      inflammatory bowel diseases, such as Crohn's disease.

PMID- 20146157
TI  - [Ultrasonographic diagnosis of a biliary-digestive fistula with gallstone ileus].
AB  - HISTORY AND CLINICAL FINDINGS: A 72-year-old woman was admitted to the hospital
      with upper abdominal pain, nausea, vomiting, and obstipation. INVESTIGATIONS:
      Percutaneous ultrasound found aerobilia, a biliary-digestive fistula, and an
      ileus with gallstones within the small bowel. The findings were confirmed at
      computed tomography. TREATMENT AND COURSE: A gallstone ileus on the basis of a
      biliary-digestive fistula was diagnosed. The patient was treated by surgery and
      with antibiotics. CONCLUSION: This case report demonstrates that percutaneous
      ultrasonography should be used as the first imaging procedure in the diagnosis of
      acute abdominal pain. This procedure makes it possible to detect a gallstone
      ileus. It is important also to define various intestinal structures accurately.

PMID- 20146158
TI  - [Influenza virus A/H1N1 infection: wrong provisional diagnosis.[corrected]].

PMID- 20146159
TI  - [43-year-old man with persisting fever and hemoptysis during antibiotic
      treatment. Acute lung embolism with infarct pneumonia].

PMID- 20146160
TI  - [Plasmodium knowlesi: cause of naturally acquired malaria in humans].

PMID- 20146161
TI  - [Glycemic control and cardiovascular benefit: What do we know today?].
AB  - It is still a much debated question whether antidiabetic therapy to target normal
      glycated hemoglobin levels would reduce cardiovascular events in patients with
      advanced type 2 diabetes. New findings result from ACCORD, ADVANCE and VADT.
      These trials reveal that microvascular and macrovascular effects of intensive
      glucose lowering have to be considered separately: Glycemic control convincingly
      demonstrated to have a protective impact on microvascular complications,
      especially nephropathy. However, macrovascular benefits remain doubtful in these
      megatrials and have to be considered in connection with the individual global
      risk. On the other hand, the Diabetes Intervention Study (DIS) and UKPDS 10-year
      follow-up results yielded better cardiovascular outcomes for those patients who
      received intensive glucose-lowering therapy very early after diabetes diagnosis,
      but the favourable influences did not manifest until a time period of 1 - 2
      decades. For the first time, the cardiovascular benefit of an antidiabetic
      substance (pioglitazone) could be verified in the large-scale outcome-trial
      PROactive for patients with advanced diabetes and multiple manifestations of
      macroangiopathy. The results provide strong support for a beneficial influence on
      macrovascular complications just under 3 years of treatment. Nevertheless, the
      positive findings did not result from better glycemic control, but from the
      complexity of effects of PPARgamma agonist pioglitazone on insulin resistance,
      lipoprotein spectrum, blood pressure, endothelial function and biomarkers of
      subclinical inflammation. It is obvious that we need to integrate such
      pleiotropic effects on metabolic syndrome and cardiovascular disease to improve
      the quality of drug-therapy decisions. This, in turn, requires a growing body of
      evidence from large, long-term outcome trials - but appropriate data are still
      unavailable for the vast majority of antidiabetic drugs.

PMID- 20146162
TI  - [LOX-1 receptor as a novel target in endothelial dysfunction and
      atherosclerosis].
AB  - Atherosclerosis with its complications like heart attack and stroke, is the most
      frequent cause of death in the industrialized countries. Oxidized low-density
      lipoproteins (LDL) play a major role in the pathogenesis of atherosclerosis.
      Inhibition of cholesterol synthesis by statins has several protective effects but
      is not sufficient to prevent the uptake of oxidized LDL and the development of
      atherosclerotic plaques. For this reason a selective pharmacological inhibition
      of the uptake of oxidized LDL (oxLDL) in endothelial cells is an interesting
      therapeutic approach. An important novel target molecule is the endothelial
      lectin-like oxLDL receptor LOX-1. This receptor is able to take up both minimally
      and highly oxidized LDL. In addition it mediates endothelial phagocytosis of aged
      and apoptotic cells and plays a role in thrombocyte adhesion and in the
      interaction between bacterial proteins and endothelial cells in sepsis. LOX-1 is
      induced by proinflammatory cytokines, oxLDL, angiotensin II, endothelin-1 and
      arterial hypertension. LOX-1 increases endothelial dysfunction and
      atherosclerosis by endothelial uptake of oxLDL. This is the reason why LOX-1 has
      been considered as a novel link between hypertension and atherosclerosis.
      Transgenic overexpression of the LOX-1 receptor and high-fat diet induces
      intramyocardial vascular disease and endothelial dysfunction in resistance
      arteries. In contrast, genetic deletion of the LOX-1 gene reduces the development
      of atherosclerotic plaques. In the clinical context LOX-1 has been detected in
      the early phase of endothelial dysfunction and atherosclerosis in arteries of
      patients with coronary heart disease. Several novel data support a role of LOX-1
      in the endothelial dysfunction in diabetic vascular and renal disease,
      hypercholesterolemia, obesity and preeclampsia. This makes the LOX-1 receptor a
      novel and interesting target molecule in endothelial dysfunction and
      atherosclerosis.

PMID- 20146163
TI  - [Process and outcome quality of the German Paediatric Surveillance Unit (ESPED)].
AB  - The German paediatric surveillance unit (ESPED) was founded in 1992 with the
      objective to generate incidence data and to describe symptoms, diagnostic
      procedures, therapy and prevention for rare paediatric diseases requiring in
      hospital treatment. Every month the ESPED office sends a mailing card to the
      heads of all paediatric departments asking for the incident diagnosis of up to 12
      conditions. In 2007 about 96% of the cards are returned. Each condition is
      represented by a principal investigator. Up till now surveillance of 52
      conditions has been performed. Reports on the mailing card prompt immediate
      mailing of the full questionnaire. For 43 conditions the return rates were in the
      range of 70-100% and for 7 conditions <70% (unknown 2). The highest return rates
      were achieved if the principal investigator was supported by staff comprising at
      least two persons or if the mailing of the questionnaire was handled by the ESPED
      office. The scientific impact of the ESPED System was assessed by the impact
      factors of the journals, in which the respective ESPED studies were published. By
      August 31 (st) 2008 the investigators of 38 studies reported up to 7 publications
      per conditions surveyed. A total of 104 publications was reported: 27 of these
      appeared in journals without an impact factor. Among the 77 other publications 10
      appeared in journals with an impact factor >10. CONCLUSION: Surveillance in ESPED
      has contributed significantly to high quality research on rare conditions in
      children.

PMID- 20146164
TI  - Radiofrequency ablation of Barrett's esophagus: outcomes of 429 patients from a
      multicenter community practice registry.
AB  - BACKGROUND AND STUDY AIMS: The use of radiofrequency ablation (RFA) for complete
      eradication of Barrett's esophagus has shown promise in trials conducted at
      predominantly tertiary academic centers; however less is known regarding outcomes
      in the community. We evaluated the safety and efficacy of RFA for Barrett's
      esophagus delivered in a community practice setting. PATIENTS AND METHODS: This
      was a multicenter registry conducted in community-based gastroenterology
      practices. Patients had confirmed intestinal metaplasia with or without dysplasia
      on biopsy of a Barrett's esophagus. Intervention was step-wise RFA with follow-up
      esophageal biopsies. Endpoints were histology-based; complete response was
      defined as all biopsies at most recent endoscopy negative for intestinal
      metaplasia (CR-IM) or dysplasia (CR-D). Three cohorts were reported: 1) safety
      cohort, all patients; 2) efficacy cohort A, patients with at least one biopsy
      session after initial treatment; 3) efficacy cohort B, patients with at least one
      biopsy session > or = 1 year after initial treatment. RESULTS: The safety cohort
      included 429 patients (71 % men, median age 59 years, median Barrett's segment
      3.0 cm). There were no serious adverse events (bleeding, perforation, death), and
      a stricture occurred after 1.1 % of cases (2.1 % of patients). In efficacy cohort
      A (n = 338), CR-IM and CR-D were achieved in 72 % and 89 % of patients,
      respectively (median follow-up 9 months). In efficacy cohort B (n = 137), CR-IM
      and CR-D were achieved in 77 % and 100 % of patients, respectively (median follow
      up 20 months). CONCLUSIONS: In this multicenter registry conducted at four
      community-based practices, the observed safety and efficacy outcomes associated
      with RFA for Barrett's esophagus are comparable to those previously reported in
      multicenter trials from predominantly tertiary academic centers.

PMID- 20146165
TI  - Precut sphincterotomy using insulated angulotome.
AB  - A newly designed insulated angulotome was evaluated in a series of patients in
      whom biliary cannulation using conventional methods had failed and who required
      precut sphincterotomy. The new device consists of an insulated glass tip to
      prevent excessive electrocautery flow, and angulation to facilitate elevation of
      the papillary roof on cutting. A prospective series of patients with cholangitis
      or obstructive jaundice with failed biliary cannulation were recruited. The
      success of cannulation and complications following endoscopic retrograde
      cholangiopancreatography were analyzed. A total of 13 patients underwent precut
      sphincterotomy using the insulated angulotome. The immediate success of gaining
      biliary access after failed cannulation was 100 %. The mean size of the common
      bile duct on ultrasonography was 8.1 mm. The mean time to achieve biliary
      cannulation was 9 minutes 4 seconds, and there was no perforation or bleeding.
      This case series showed that precut sphincterotomy with the insulated angulotome
      can be safely performed without major complications.

PMID- 20146166
TI  - A novel missense mutation (C84R) in a patient with type II vitamin d-dependent
      rickets.
AB  - A 7-year-old boy with severe rickets that by clinical analysis was diagnosed as
      affected by type II vitamin D-dependent rickets, was evaluated for mutations in
      the vitamin D receptor gene (VDR). The molecular analysis showed a homozygous
      state for a novel missense mutation (C84R) in a highly conserved nucleotide in
      the second Zn finger of the DNA binding domain.

PMID- 20146167
TI  - Assessment of adrenal functions in patients with autosomal dominant polycystic
      kidney disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
      common hereditary kidney disease and extrarenal manifestations may be observed in
      many organ systems. Hypothalamus-pituitary-adrenal axis was not evaluated
      extensively in patients with ADPKD. We aimed to evaluate this axis in these
      patients. METHODS: Twenty two patients with ADPKD and 27 healthy subjects were
      enrolled. Basal dehydroepiandrosterone sulfate (DHEAS) levels and cortisol and
      DHEA responses to low dose short adrenocorticotropin stimulation test were
      assessed. Correlation analyses of these parameters with glomerular filtration
      rates (GFR), renal volumes and pain characteristics in patients with ADPKD were
      performed. RESULTS: Patients with ADPKD had higher basal cortisol levels (12.1 +/
      3.4 vs. 9.6 +/- 4.3 MUg/dL, p=0.033), and higher basal cortisol/DHEAS ratios
      (0.073 +/- 0.05 vs. 0.045 +/- 0.02, p=0.015) compared to controls. None of the
      subjects had inadequate response to adrenocorticotropin stimulation. Patients
      with ADPKD had lower delta cortisol (absolute increase between peak and basal)
      levels (10.3 +/- 2.8 vs. 12.6 +/- 4.2 MUg/dL, p=0.026) compared to controls.
      Subgroup analysis showed that significant differences existed only between female
      patients and female controls. There was no significant correlation between
      cortisol levels and renal volumes or GFR. A significant correlation was found
      only between delta cortisol and pain frequency in female patients. CONCLUSIONS:
      Patients with ADPKD had higher basal cortisol levels, higher basal cortisol/DHEAS
      ratios and lower delta cortisol levels compared to controls, indicating promptly
      stimulated zona fasciculata function. Further studies are needed to confirm these
      results and to investigate possible underlying mechanisms.

PMID- 20146168
TI  - Effect of growth hormone (GH) on fasting and postprandial metabolism in GH
      deficiency.
AB  - OBJECTIVE: Hypopituitarism with adult-onset growth hormone deficiency (GHD) is
      associated with increased cardiovascular morbidity and mortality due to premature
      and progressive atherosclerosis. An underlying cause of atherosclerosis is
      increased insulin resistance. Elevated fasting and postprandial glucose and lipid
      levels may contribute to premature atherosclerosis. We studied effects of growth
      hormone replacement (GHRT) on fasting and postprandial metabolic parameters as
      well as on insulin sensitivity in patients with adult-onset GHD. DESIGN: Using a
      standardized mixed meal, we studied insulin, glucose, non-esterified free fatty
      acid (NEFA) and triglycerides (TG) concentrations in the fasting state and during
      a 4 h postprandial period in 15 patients with adult-onset GHD before and after 4
      months of GHRT. Identical investigations were performed in healthy matched
      control subjects. RESULTS: GHD patients before and after GHRT: GHRT did not
      result in significant changes in fasting glucose, insulin, NEFA and TG
      concentrations. In the postprandial period GHRT resulted in a non-significant
      increase in glucose and a decrease in NEFA levels in the presence of unchanged
      postprandial insulin and TG concentrations. GHD patients vs. control subjects:
      GHD patients showed similar fasting glucose, insulin and NEFA concentrations, but
      TG were increased. In the postprandial period GHD patients exhibited similar
      glucose and TG, but increased insulin and NEFA concentrations. GHRT patients vs.
      control subjects: Patients after GHRT had similar fasting glucose, insulin and
      NEFA, but increased TG concentrations. In the postprandial period patients after
      GHRT had increased glucose and insulin levels in the presence of similar NEFA and
      TG concentrations. CONCLUSIONS: While impaired insulin action in patients with
      GHD translates mainly by an impaired fasting TG metabolism, GHRT induced insulin
      resistance additionally encompasses postprandial glucose metabolism.

PMID- 20146169
TI  - Comparison of the effects of atorvastatin and simvastatin in women with
      polycystic ovary syndrome: A prospective, randomized study.
AB  - Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, insulin
      resistance (IR), and chronic inflammation. Simvastatin improves
      endocrine/clinical aspects of PCOS and decreases systemic inflammation in PCOS.
      There have been no comparative studies carried out regarding the effects of
      different statin treatment in PCOS. We aimed to assess the effects of two
      different statin treatments on various metabolic, endocrine, oxidative and
      inflammatory factors in PCOS. DESIGN: Prospective, randomized clinical trial
      METHODS: Sixty-four (64) women with PCOS were included in the study. Group 1 had
      (atorvastatin, 20lmg daily; n=32) or group 2 had (simvastatin, 20l mg daily
      n=32). The metabolic, endocrine, inflammatory and oxidative profiles were
      evaluated. RESULTS: Group 1 resulted in a significant reduction in the HOMA index
      and fasting insulin (-26.9+/-9.6%, -26.2+/-10.8%, P<0.01, respectively).CRP
      levels decreased by 63.6+/-15.9% in group 1 (P<0.01), whereas in the group 2 it
      decreased by 34.6+/-10.7% (P<0.05). Serum levels of LH declined by 19.1+/-4.5%
      (P<0.05) in the group 1 and by 39.3+/-11.9% (P<0.01) in the group 2. FAI
      decreased by -20+/-9.9% in group 1 (P<0.05) and it decreased by -38.7+/-13.8% in
      the group 2 (P<0.01). MDA levels decreased by 32.6+/-9.6% in group 1 (P<0.05),
      whereas in the group 2 it decreased by 30.3+/-10.9% (P<0.01). HOMA index and
      fasting insulin showed a reduction but not reached statistically significance in
      the group 2 (8.3+/-1.9%, 3.0+/-0.8%, P>0.05, respectively). CONCLUSION: Both the
      statins are effective in reducing inflammation, hyperandrogenemia, oxidative
      stress and metabolic parameters. While atorvastatin has more noticeable effects
      on fasting insulin and insulin sensitivity, simvastatin has a dominant effect on
      total T in PCOS women.

PMID- 20146170
TI  - Association of LPR5 polymorphism with bone mass density and cholesterol level in
      population of Chinese Han.
AB  - Recently, two single nucleotide polymorphisms, rs4355801 near the osteoprotegerin
      (OPG) gene and rs3736228 in the low-density lipoprotein receptor-related protein
      5 (LRP5) gene, were found to be associated with osteoporosis and osteoporotic
      fractures in Caucasians in a genome wide association study. In the present study,
      we investigated the association between these two SNPs (rs4355801 and rs3736228)
      and bone mass density (BMD), whole body T score and metabolic phenotypes (e. g.,
      body mass index, glucose, triglyceride, and total cholesterol) in 425 Chinese Han
      subjects. We observed a significant association between rs3736228 in LRP5 and hip
      BMD, total BMD, and T score. The level of hip BMD, total BMD, and T score was
      significantly reduced with the number of at risk T alleles (p=0.006, p=0.003, and
      p=0.006, respectively). This finding was still significant after accounting for
      gender and age. We also observed a significant association between rs3736228 and
      total cholesterol (CHO) levels in our sample. The CHO levels of the CC, CT, and
      TT genotypes were 4.71, 4.76, and 5.24, respectively (p=0.031). For OPG
      rs4355801, the level of hip BMD, spine BMD, and total BMD was consistently
      reduced in persons with the copy of A allele, but none of these findings were
      statistically significant. We also did not observe a significant association
      between the above two polymorphisms and body mass index, glucose, and
      triglyceride levels in Chinese Han subjects. Thus, our observations support the
      association between rs3736228 and BMD in Han subjects. We also provide first
      evidence that the T allele of rs3736228 increases the total cholesterol level in
      a general Han population.

PMID- 20146171
TI  - Human multidrug resistance-1 gene expression levels in graves-basedow disease.
AB  - OBJECT: Multidrug resistance 1 gene is responsible for the resistance of a large
      variety of drugs in human cells. We tried to evaluate this in the present study
      in thyroid stimulant hormone receptor antibody positive subjects. METHOD: In
      study enrolled 23 female and 10 male subjects. Hyperthyroid subjects were treated
      with PTU and remission was assured between 6-12 months. Blood samples were
      collected before the start of this treatment. Permission for this study was taken
      from the patients and the local ethical committee. RESULTS: Serum F-T3, F-T4
      levels in Graves subjects were markedly high, whereas TSH levels were markedly
      low than normal range. We also found that with increased age of the Graves'
      subjects, MDR-1 gene expression decreased. There was also a direct correlation
      between blood MDR-1 gene expression and TSH-R Ab levels in patients with Graves's
      disease. We observed that the duration of being euthyroid was lengthened with the
      elevation of MDR-1 gene expression. There was a direct correlation between blood
      MDR-1 gene expression levels and ultrasonografic size of thyroid gland.
      CONCLUSION: As a result, raised blood MDR-1 gene expression levels in patients
      with Graves-Basedow disease may be associated with the activity of the disease
      and the resistance to its treatment. The more blood MDR-1 expression increases
      the more the duration of being euthyroid increases.

PMID- 20146172
TI  - [Causes and course of fornix rupture].
AB  - PURPOSE: Fornix rupture is a urological emergency situation. In most cases
      ureteral stones represent the underlying cause. We present the largest series
      ever reported. MATERIAL AND METHODS: Between 1994 bis 2005 a total of 162
      patients were diagnosed with a fornix rupture. There were 121 men and 41 women
      with a median age of 53 years (range: 20-79 years). We investigated the following
      parameters: underlying cause of fornix rupture, symptoms, diagnostic and
      therapeutic procedures. RESULTS: In 60% of cases a ureteral stone was found as
      cause and in another 28% we found no reason for fornix rupture. 93% of patients
      had one or more symptoms at the time of diagnosis. In all patients primary
      endoscopic therapy (96%) or insertion of a nephrostomy tube was performed (4%).
      Also, antibiotic treatment was given in 92% of patients. No patient developed a
      perirenal abscess or other relevant complication requiring open operative
      revision. CONCLUSIONS: We confirm that ureteral stones are the most frequent
      causes of fornix rupture. With a low pressure system and antibiotic treatment,
      secondary complications can be effectively prevented.

PMID- 20146174
TI  - Hypoxia-ischemia brain damage disrupts brain cholesterol homeostasis in neonatal
      rats.
AB  - PURPOSE: The first 3 weeks of life is the peak time of oligodendrocytes
      development and also the critical period of cholesterol increasing dramatically
      in central nervous system in rats. Neonatal hypoxia-ischemia (HI) brain damage
      happening in this period may disturb the brain cholesterol balance as well as
      white matter development. MATERIALS AND METHODS: To test this hypothesis,
      postnatal day 7 (P7) Sprague-Dawley rats were subjected to HI insult. Cholesterol
      concentrations from brain and plasma were measured. White matter integrity was
      evaluated by densitometric analysis of myelin basic protein (MBP) immunostaining
      and electron microscopy. Brain TNF-alpha and IL-6 levels were also measured.
      RESULTS: HI-induced brain cholesterol, but not the plasma cholesterol, levels
      decreased significantly during the first three days after HI compared with naive
      and sham operated rats (p<0.05). Obvious hypomyelination was indicated by marked
      reductions in MBP immunostaining on both P10 and P14 (p<0.01) and less and
      thinner myelinated axons were detected on P21 by electron microscopy observation.
      High expressions of brain TNF-alpha and IL-6 12 h after HI (p<0.05) were also
      observed. DISCUSSION: The present work provides evidence that HI insult destroyed
      brain cholesterol homeostasis, which might be important in the molecular
      pathology of hypoxic-ischemic white matter injury. Proinflammatory cytokines
      insulting oligodendrocytes, may cause cholesterol unbalance. Furthermore,
      specific therapeutic interventions to maintain brain cholesterol balance may be
      effective for the recovery of white matter function.

PMID- 20146175
TI  - A syndrome with coarse face, mental retardation and unusual stereotyped
      movements*.
AB  - We describe a mentally retarded 24-year-old man followed by our group since age
      18 months who exhibited nearly continuous stereotypic movements while awake.
      These movements, which have persisted over many years, consist of synchronous
      lateral flexion at the neck and waist. Movements could be partially voluntarily
      suppressed and disappeared in sleep. The patient has drug-resistant seizures and
      a constellation of dysmorphic features, including coarse face, large nose, large
      thin lips, brachicephaly, marked hirsutism on the face, and limbs proportionally
      smaller than the trunk, which suggests that the unusual stereotypic movements
      described may be part of a syndrome. Routine and full metabolic serum and urine
      analyses, full ophthalmological examination, internal organs ultrasound
      examination, full skeletal survey, standard karyotype and array-CGH analysis
      yielded normal results.

PMID- 20146176
TI  - [Obesity: is it an eating disorder?].

PMID- 20146177
TI  - [A Flemish chair in Addiction Psychiatry and the attractiveness of a psychiatric
      carrier choice].

PMID- 20146178
TI  - [Comorbid anxiety disorders and alcohol-related disorders in a population of
      bipolar I disorder: investigation in a Flemish population].
AB  - BACKGROUND: Bipolar I disorder (bp i) is a very debilitating psychiatric disorder
      which is frequently associated with comorbid psychiatric and somatic disorders.
      Many studies in other countries show strongly elevated prevalences of anxiety
      disorders and alcohol-related disorders in the bp i population, but so far no
      data on this topic are available with regard to the Flemish population. AIM: To
      determine the prevalence of anxiety disorders and alcohol-related disorders in a
      Flemish population of bp i outpatients in remission and to find out whether
      comorbidity of these disorders is linked to the onset of the disorder at a
      younger age. METHOD: Sixty-nine bp i patients in remission were given structured
      interviews at home and the results were compared with the Belgian prevalence
      reported in the European Study of the Epidemiology of Mental Disorders (esemed)
      project. results Both the prevalence of the alcohol-related disorders (15 of 69
      patients or 21.7%) and the prevalence of anxiety disorders (17 patients or 24.6%)
      were elevated compared to the general population (8.1 and 13.2% respectively).
      Among the anxiety disorders the prevalence was elevated for panic disorder,
      social phobia and post-traumatic stress disorder. No significant association was
      found between the comorbidity and the patient's age at the onset of the illness.
      CONCLUSION: The prevalence of anxiety disorders and alcohol-related disorders in
      an outpatient population of Flemish patients with bp i in remission is elevated.

PMID- 20146179
TI  - [Cognitive-behavioural therapy for primary insomnia: effectiveness in a clinical
      setting].
AB  - BACKGROUND: The effectiveness of cognitive behavioural therapy for insomnia (cbt
      i) has been demonstrated in randomised controlled trials (rct's) with primary
      insomnia patients and, more recently, with comorbid insomnia patients. The
      clinical impact of the treatment is mainly on sleep quality and the use of
      medication and to a lesser extent on daytime functioning. So far there have been
      very few studies of the effectiveness of cbt-i in clinical settings. AIM: To
      examine the effectiveness of cbt-i for primary insomnia via an uncontrolled
      prospective study in a clinical tertiary care setting. METHOD: We included 76
      patients with primary insomnia, most of whom having been referred by their gp or
      medical specialist to the Leuven University Centre of Sleep, who followed a 6
      week course of cbt-i as a group. Effects of cbt-i on primary and secondary
      outcome measures were studied. results cbt-i resulted in a significant
      improvement in all primary sleep variables such as sleep onset, sleep efficiency
      and sleep quality. The increase in total sleep time was less substantial,
      probably as a result of the specific sleep restriction guidelines. There was also
      a significant improvement on several secondary parameters, in particular
      dysfunctional cognitions, affective state, general health and use of medication.
      CONCLUSIONS: cbt-i has a significant impact on sleep quality, medication use and
      daytime functioning in primary insomniacs in a clinical tertiary care setting.

PMID- 20146181
TI  - [Cognitive behavioural therapy for schizophrenia].
AB  - BACKGROUND The publication of the Dutch multidisciplinary guidelines
      Schizophrenia and the launching of the Breakthrough project on schizophrenia led
      by the Trimbos Institute in 2006 aroused considerable interest in the Netherlands
      for the implementation of cognitive behavioural therapy for patients with
      schizophrenia. One of the reasons was that pharmacotherapy has its limitations in
      the treatment of schizophrenia; an antipsychotic drug does not lead to an
      adequate decrease in psychotic symptoms in all patients; cognitive behavioural
      therapy is then added as a form of psychotherapy. The effectiveness of cognitive
      behavioural therapy has been described in meta-analyses. AIM: To ascertain the
      efficacy of cognitive behavioural therapy for the treatment of schizophrenia and
      to give advice on how this therapy can be implemented. METHOD: We reviewed
      relevant articles and meta-analyses via PubMed and Ovid using the search terms:
      'cognitive behavioural therapy', 'continuity/psychosis', 'implementation',
      'metaanalysis', 'nurse therapist', 'psychosis' , 'schizophrenia'. results Many
      randomised controlled trials show the effectiveness of cognitive behavioural
      therapy in the treatment of schizophrenia. At the moment, the encouraging results
      of scientific research are not being adequately transferred to clinical practice.
      However, the performance of special interventions by trained nurses is making
      implementation feasible. CONCLUSION: Cognitive behavioural therapy is an
      effective treatment for schizophrenia. It is advisable that this type of therapy
      be made available to patients, in accordance with their specific needs.

PMID- 20146180
TI  - [Omega-3 and omega-6 fatty acids in the treatment of children and adolescents
      with ADHD].
AB  - Background There is a growing trend towards the use of alternative forms of
      treatment for attention deficit hyperactivity disorder (adhd), such as the food
      supplements omega-3 and omega-6 fatty acids. AIM: To study biochemical aspects,
      important hypotheses regarding the role of these fatty acids in brain
      development, the mode of operation and research results concerning the
      effectiveness of treating adhd with these supplements. METHOD: A Medline search
      was performed using the Mesh-term 'fatty acids' and the search terms 'omega-3 and
      omega-6 fatty acids' and 'attention deficit hyperactivity disorder'. results Some
      rct's (randomised controlled trails) involving children with adhd didn't show any
      improvement after treatment with omega-3 and omega-6 fatty acids. Some other
      rct's, however, did show a reduction in adhd symptoms and learning difficulties,
      but the children concerned had not been officially diagnosed with adhd. A recent
      rct showed a substantial reduction in adhd symptoms in children with the
      inattentive type of adhd and in children with adhd and comorbid problems.
      CONCLUSION: There are indications that there is a theoretical rationale for the
      effectiveness of fatty acids in the treatment of adhd; research is ongoing. At
      the moment, however, treatment of adhd with omega-3 and omega-6 fatty acids is
      not recommended because it does not qualify as being evidence-based.

PMID- 20146182
TI  - [Screening of adults with schizophrenia for metabolic complications caused by
      atypical antipsychotics].
AB  - Mortality in schizophrenic patients is clearly higher than in the general
      population. One of the reasons is the higher prevalence of the lethal side
      effects of antipsychotics: diabetic ketoacidosis, prolonged qt-c time and gastro
      intestinal hypomotility associated with clozapine are three serious side-effects
      which sometimes prove fatal. Systematic screening, however, means that
      sideeffects can be diagnosed at an earlier, less severe stage, leading to higher
      rates of survival and remission. This should contribute to a normalising of the
      mortality rate.

PMID- 20146183
TI  - [Hallucinations and vivid dreams by use of metoprolol].
AB  - A 71-year-old man had had visual hallucinations and vivid dreams for two years
      after starting to take metoprolol. When metoprolol was replaced by atenolol the
      patient's symptoms disappeared within five days. Side-effects of beta-blockers on
      the central nervous system are relatively uncommon. The mechanisms underlying
      these side-effects are not fully understood. Lipophilic beta-blockers can cross
      the blood-brain barrier, whereas hydrophilic beta-blockers cannot. Doctors need
      to be alerted to the varying side-effects of specific beta-blockers.

PMID- 20146184
TI  - [Zonisamide in the preventive treatment of refractory migraine].
AB  - INTRODUCTION: Chronic migraine refractory to preventive treatment is a common
      clinical situation in general neurology clinics. The aim is to analyse our
      experience with zonisamide in the preventive treatment of patients with frequent
      refractory migraine. PATIENTS AND METHODS: Those patients with no response or
      intolerance to topiramate and at least one more preventative received zonisamide.
      This drug was increased 25 mg per week up to 200 mg/day. The efficacy of
      zonisamide was evaluated in terms of 'response' (reduction in attack frequency
      below 50%) at the third month of treatment. RESULTS: Our series comprises a total
      of 172 patients, with ages ranging from 22 to 69 years. 85% were women. The final
      dosage of zonisamide was 50-200 mg/day, with the 100 mg/day being the most
      frequently administered dose. Zonisamide was efficacious (response) in 76 (44%)
      patients; response being excellent in 22 (13%). MIDAS score was reduced by 43.2%.
      Zonisamide was not tolerated by 27% of the patients, mainly due to subjective
      mental slowness or digestive symptoms. CONCLUSIONS: These results, obtained in a
      big sample of patients refractory or intolerant to topiramate and other
      preventatives, indicate that, at least in conditions of daily clinical practice,
      zonisamide, at relatively low dosages, is an option to be considered for the
      preventive treatment of patients with frequent migraine.

PMID- 20146185
TI  - [Diffusion-weighted imaging in pediatric central nervous system infections].
AB  - INTRODUCTION: Central nervous system (CNS) infections are associated with high
      morbidity and mortality. Neuroimaging plays an important role in the early
      diagnosis and characterisation of neurological complications. AIM: To report the
      findings in diffusion-weighted images (DWI) and its potential contribution to the
      early diagnosis and prognosis of neurological sequelae. PATIENTS AND METHODS:
      Descriptive study of a series of 23 patients, between the ages of 1 month and 16
      years, who presented with CNS infection. MRI, with DWI, was performed in all of
      them. RESULTS: We found 13 viral meningoencephalitis and 10 bacterial meningitis.
      MRI was performed from day one to seventh after hospitalization. We found CNS
      affection in conventional MRI and/or DWI in 14 of 23 cases (60%). In three
      patients the neurological injury was only evident in DWI. We found any type of
      neurological sequelae in 17 of 21 evaluable patients. The most common
      neurological sequelae we found was epilepsy (9 of 21). When we related sequelae
      with conventional MRI and DWI we found a trend in associated more severe sequelae
      when there are pathological findings in neuroimaging, not statistically
      significant. CONCLUSIONS: DWI sequence can be useful in the early diagnosis of
      neurological complications in CNS infections.

PMID- 20146186
TI  - [Clinical characterisation and course following therapeutic intervention for
      swallowing disorders in hospitalised paediatric patients].
AB  - INTRODUCTION: Swallowing disorders are common in hospitalised patients and are an
      added difficulty when it comes to discharging them from hospital. Suitable
      characterisation performed by means of assessments conducted by a neurologist and
      a speech and language therapist allows for more accurate therapeutic decision
      making. AIM: To describe swallowing disorders from the speech and language
      therapy evaluation performed on admission until discharge in paediatric patients
      and their relation with the therapeutic intervention that was implemented.
      PATIENTS AND METHODS: We performed a retrospective analysis consisting in the
      examination of the medical records of 38 paediatric patients hospitalised between
      May 2007 and June 2008. Functional clinical evaluation was carried out in 100% of
      patients, and a video swallow study was conducted in 34%. Swallowing disorders
      were characterised as mild, moderate and severe, according to the stage that was
      altered and aspiratory risk to the airway. A speech therapist provided
      therapeutic intervention, and parents and caregivers were given special training.
      RESULTS: Swallowing disorders were chiefly associated to prematurity. The most
      frequently used therapeutic techniques were: tactile stimulation, providing
      patterns and training of parents. In the speech and language therapy evaluation
      performed on admission, 37% of disorders were severe, 21% were moderate and 42%
      were mild disorders. In most of the newborn infants, progress was favourable, as
      shown by a shift to normal swallowing in 48% and to mild in 8%. In the 17 preterm
      newborn infants, there was a change to normal swallowing in 65% and to mild in
      12%. CONCLUSIONS: Swallowing disorders in this group of patients is mainly
      associated to prematurity. Systematic therapeutic intervention would help in the
      recovery from swallowing disorders, especially in preterm newborn infants.

PMID- 20146187
TI  - [Homocysteine and cognitive impairment in Parkinson's disease].
AB  - INTRODUCTION: The relationship between homocysteine (Hc) and vascular diseases
      has been known for more than 30 years. Lately, Hc has also been related to
      cognitive and motor impairment. In Parkinson's disease (PD), chronic treatment
      with levodopa could induce higher levels of Hc, and thus may increase risk of
      cognitive impairment. AIMS: To confirm that PD patients treated with levodopa
      have higher levels of Hc and to establish a relationship between Hc, folic acid
      and vitamin B12 levels. Also, we studied a possible link between those variables
      and cognitive function. PATIENTS AND METHODS: 58 patients with diagnosis of PD
      were included (45 under treatment with levodopa). Basal levels of Hc, vitamin B12
      and folic acid were determined. Forty five patients underwent neuropsychological
      evaluation. RESULTS: Hc levels were significantly higher in patients taking
      levodopa and were not related to levodopa dosage or treatment duration. There was
      a negative correlation between Hc levels and those of vitamin B12 and folic acid
      in men but we found no such correlation in women. Entacapone was not found to
      reduce Hc levels. Hc levels were significantly higher in patients with cognitive
      impairment (9 out of 45 patients). CONCLUSIONS: Our study confirms presence of
      high levels of Hc in PD patients under treatment with levodopa, more evident in
      patients with cognitive impairment.

PMID- 20146188
TI  - [Relearning vocabulary. A comparative analysis between a case of dementia and
      Alzheimer's disease with predominant compromise of language].
AB  - INTRODUCTION: Semantic dementia is characterised by a progressive loss of
      semantic content that initially affects the capacity to name things, and is
      associated with asymmetric atrophy of the anterior temporal lobes. In Alzheimer's
      disease (AD) with predominant compromise of language, anomia is also the main
      symptom. The study examined the capacity to relearn vocabulary of two patients,
      each exhibiting one of these two forms of degenerative anomia. CASE REPORTS: The
      two cases presented similar ages, gender, levels of schooling and degree of
      compromise. Their capacity to name a list of 40 pictures was evaluated at
      baseline, following 20 sessions of relearning, at one month and at six months.
      The patient with semantic dementia named 25/40 objects at baseline, 40/40 after
      relearning, 35/40 at one month and 27/40 at six months. The patient with AD named
      29/40 at baseline, 30/40 after relearning, 29/40 at one month and 32/40 at six
      months. No intrusions were observed following relearning. CONCLUSIONS: The
      patient with semantic dementia was able to relearn all the vocabulary she was
      shown, even though she lost everything she had acquired after treatment was
      interrupted. The AD patient did not improve her naming capacity with therapy.
      These differences suggest that the learning and consolidation circuits are
      affected in different ways. Subjects with semantic dementia, but not those with
      AD, could benefit from word relearning strategies with this method.

PMID- 20146189
TI  - [Pudendal nerve entrapment syndrome].
AB  - INTRODUCTION: Pudendal nerve entrapment syndrome is a poorly known condition and
      thus rarely included in our differential diagnoses. First described by Amarenco
      in 1987. DEVELOPMENT: The symptomatology is varied and can be confused with other
      entities, in particular the pelvic floor myofascial syndrome. CONCLUSIONS: The
      main symptom is neuropathic pain in the perineal area. The diagnosis is based on
      the clinical history, physical examination and the confirming neurophysiologic
      tests.

PMID- 20146190
TI  - [The effectiveness of cognitive-behavioural therapy in affective and anxiety
      disorders using functional neuroimaging].
AB  - INTRODUCTION: In the last decades psychological studies have demonstrated the
      effectiveness of the cognitive-behavioural therapy for most anxiety and
      depressive disorders. Recently, a different and complementary approach in terms
      of validation of cognitive-behavioural therapy has emerged: testing the efficacy
      of these therapies using functional neuroimaging techniques. DEVELOPMENT:
      Neurological studies evaluate the cerebral functioning causing the appearance of
      symptoms and monitoring the brain activity. In this revision study we show the
      implications of different brain structures (amygdala, cingulate cortex, thalamus,
      insula) with the characteristic symptoms of many mental disorders studied
      (obsessive-compulsive disorder, specific phobia, etc.) and the neurological
      changes after applying a cognitive-behavioural therapy. CONCLUSIONS: At the
      present there is a very limited number of studies due to the complexity in
      implementing this type of researches. However, data suggest changes in metabolic
      activity after cognitive-behavioural therapy at the same time as the decrease of
      symptoms. Future studies should control the influence of variables such as
      comorbidity and medication, which prevent more definitive conclusions.

PMID- 20146191
TI  - [Neuroscience and education: towards the construction of interactive bridges].
AB  - INTRODUCTION: The debates on the potential interdisciplinary association between
      neuroscience and education began approximately three decades ago. In order for
      the integration of neuroscientific and educational knowledge to impact on
      learning and teaching it would imply the consideration of the emergence of
      several cognitive and emotional processes during development, and the possibility
      to influence them through specific interventions. AIM. To examine epistemological
      and methodological implications and bridging requirements in the interaction
      between neuroscience, cognitive psychology and education. DEVELOPMENT: A dynamic
      interdisciplinary bridging consists in the identification and reduction of
      different epistemological, methodological, technological and practical gaps
      between those disciplines. Furthermore, the consideration of complex phenomena,
      such as human development and learning processes in terms of multiple levels of
      analysis, may contribute to the enrichment of a critical dialogue, but also to
      generate genuine integrated interventions. Historical and current conceptual
      perspectives attempting to bridge neuroscience and education are described.
      CONCLUSIONS: At present, interdisciplinary efforts between neuroscience and
      education are at a preliminary stage. In this context, bridging requires
      conceptual and methodological approaches that consider the complexity of
      developmental and learning phenomena and the participation of actors from
      different fields, instead of unique bridges. This paper intends to consider
      several basic principles aimed at developing a dynamic integration that assesses
      the complexity of development, learning and teaching processes.

PMID- 20146192
TI  - [Giant epicranial pseudocyst following disconnection from a ventriculoperitoneal
      shunt system].

PMID- 20146193
TI  - [Different faces of levodopa-responsive dystonia].

PMID- 20146194
TI  - [The feeling that time is speeding up: diagnostic problems].

PMID- 20146195
TI  - [Contiguous gene deletion syndrome in Xp21].

PMID- 20146196
TI  - An evaluation of a problem-based learning experience in an occupational therapy
      curriculum in the UK.
AB  - The objectives of the study was to evaluate an adapted approach to problem-based
      learning (PBL) on a pre-registration Masters course in Occupational Therapy at
      the University of East Anglia in the UK. The adaptation, named placement PBL,
      required students to write and select the material based on their placement
      experiences, for the cohort's learning. The evaluation purpose was to determine
      the students' views of the efficacy of placement PBL for facilitating their
      learning in the final 3 months of their pre-registration education. Placement PBL
      was evaluated using both questionnaires and focus groups, with two cohorts of
      students for data collection. Placement PBL was seen to provide current, relevant
      and complex learning scenarios that help students to move from a theoretical
      understanding to application of theory in the complexity of actual service
      situations. The authors conclude that placement PBL has the potential to prepare
      students for the transition from student to qualified practitioner. Both
      researchers were also the PBL tutors which may have affected the students'
      honesty in their feedback. Further research is indicated for ongoing evaluations
      of the effectiveness of PBL in helping students to become confident occupational
      therapy clinicians, and comparative studies with other learning approaches.

PMID- 20146197
TI  - Evaluation of cognitive technologies in geriatric rehabilitation: a case study
      pilot project.
AB  - The aim of this study was to develop and evaluate low-cost technology for
      cognitive rehabilitation in older individuals with dementia and document changes
      stemming from a clinical case study using these tools. An activity board, a
      calendar, a routine organizer and a software program were used and evaluated by
      specialists (n = 7). A pre-post-case study with an elderly male with dementia was
      undertaken for four months. All rehabilitation resources were classified as
      appropriate by the specialists. Post-intervention scores demonstrated improvement
      in cognitive functioning and daily activities at home. There is a need for
      further research to assess the therapeutic effects in patients with dementia
      applying equipment and software to improve cognitive function.

PMID- 20146198
TI  - Contamination and harm relevant UCS-expectancy bias in spider phobic individuals:
      influence of treatment.
AB  - Phobic individuals expect aversive UCS's following encounters with phobic
      stimuli. Previous research using a thought-experiment procedure showed that
      contamination rather than harm-related outcome expectancies differentiated best
      between high and low spider fearful undergraduates. This study investigated the
      alleged role of these UCS-expectancy biases in the maintenance of phobic
      complaints. First, this study sought to replicate these earlier findings in a
      community sample of high spider fearful individuals who applied for treatment (n
      = 60) and a sample of low spider fear controls (n = 30). Second, the present
      study tested if UCS-expectancies disappear following successful treatment and
      whether there were any differences between harm and contamination-related UCS
      expectancies in this respect. If contamination- and/or harm-related UCS
      expectancy biases play a critical role in the maintenance of spider fear, these
      biases should be substantially reduced after successful treatment. The results
      showed that spider fearful individuals associated spiders relatively strongly
      with both harm- and contamination-related outcomes. Consistent with the alleged
      reciprocal relationship between phobic fear and UCS expectancy bias, both types
      of biased expectancies were effectively reduced following treatment.

PMID- 20146199
TI  - Study of the Socratic method during cognitive restructuring.
AB  - Cognitive restructuring, in particular in the form of the Socratic method, is
      widely used by clinicians. However, little research has been published with
      respect to underlying processes, which has hindered well-accepted explanations of
      its effectiveness. The aim of this study is to present a new method of analysis
      of the Socratic method during cognitive restructuring based on the observation of
      the therapist's verbal behaviour. Using recordings from clinical sessions, 18
      sequences were selected in which the Socratic method was applied by six cognitive
      behavioural therapists working at a private clinical centre in Madrid. The
      recordings involved eight patients requiring therapy for various psychological
      problems. Observations were coded using a category system designed by the authors
      and that classifies the therapist's verbal behaviour into seven hypothesized
      functions based on basic behavioural operations. We used the Observer XT software
      to code the observed sequences. The results are summarized through a preliminary
      model which considers three different phases of the Socratic method and some
      functions of the therapist's verbal behaviour in each of these phases:
      discriminative and reinforcement functions in the starting phase, informative and
      motivational functions in the course of the debate, and instructional and
      reinforcement functions in the final phase. We discuss the long-term potential
      clinical benefits of the current proposal. 

PMID- 20146200
TI  - Reasoning, delusion proneness and stress: an experimental investigation.
AB  - Previous studies have been inconsistent in demonstrating a relationship between
      delusion proneness and induced stress on reasoning biases. The present study was
      an experimental investigation of the role of stress in the form of feeling
      rushed, which has previously been shown to be related to the jumping-to
      conclusions reasoning bias for delusion-prone individuals, on the reasoning of
      delusion-prone individuals. University students (n = 133) completed a measure of
      delusion proneness and were randomly assigned to either receive or not receive a
      stress induction in the form of a speeded subtraction task. All participants
      engaged in four trials of a probabilistic reasoning task. Delusion-prone and not
      delusion-prone participants performed similarly when there was no stress
      induction, but delusion-prone individuals demonstrated reasoning biases relative
      to not delusion-prone individuals when stress was induced. The reasoning of
      delusion-prone individuals may be particularly vulnerable when they feel rushed
      and in stressful conditions.

PMID- 20146201
TI  - Usefulness of a trauma-focused treatment approach for travel phobia.
AB  - Despite its prevalence and potential impact on functioning, there are
      surprisingly little data regarding the treatment responsiveness of travel phobia.
      The purpose of this non-randomized study was to evaluate the usefulness of a
      trauma-focused treatment approach for travel phobia, or milder travel anxiety
      arising as a result of a road traffic accident. Trauma-focused Cognitive
      Behavioural Therapy (TF-CBT), and Eye Movement Desensitization and Reprocessing
      were used to treat a sample of 184 patients, who were referred to a psychological
      rehabilitation provider. Patients in both treatment groups were encouraged to
      encounter their feared objects and situations between sessions. Specific (i.e.,
      travel) phobia was diagnosed in 57% of cases. Patients in both treatment
      conditions showed equally large, and clinically significant, decreases in
      symptoms as indexed by three validated measures (Impact of Event Scale, Hospital
      Anxiety and Depression Scale, and General Health Questionnaire), therapist
      ratings of treatment outcome, and a return to driving or travelling by car or
      motorbike. These improvements were obtained within an average course of 7.3
      sessions of 1 hour each. Patients with travel phobia responded with a greater
      reduction of anxiety and post-traumatic stress disorder symptoms than those with
      milder travel anxiety. Passengers reported higher levels of trauma symptoms than
      drivers, but no difference in effectiveness of treatment was found between these
      groups. The results suggest that trauma-focused psychological interventions can
      be a treatment alternative for patients with travel anxiety. Given the
      seriousness of the clinical problems related to road traffic accidents more
      rigorous outcome research is warranted and needed.

PMID- 20146202
TI  - Patients' and providers' perspectives on bibliotherapy in primary care.
AB  - Bibliotherapy is a form of self-administered treatment in which structured
      materials provide a means to alleviate distress. Although the treatment has
      evidence of effectiveness, evaluations of bibliotherapy have typically focused on
      outcomes, and the perspectives of both the client and the service provider have
      been understudied. In the present study, eleven users of a bibliotherapy scheme
      were interviewed regarding their experiences of bibliotherapy. In addition, five
      referring practitioners to the scheme were also interviewed. Thematic analyses
      revealed three super-ordinate themes in the transcripts: participants' personal
      experiences of the bibliotherapy scheme factors that facilitate change and the
      influence of the professionals involved. The implications of these findings for
      bibliotherapy schemes are considered.

PMID- 20146203
TI  - Blinded sample size reestimation with count data: methods and applications in
      multiple sclerosis.
AB  - Sample size estimation in clinical trials depends critically on nuisance
      parameters, such as variances or overall event rates, which have to be guessed or
      estimated from previous studies in the planning phase of a trial. Blinded sample
      size reestimation estimates these nuisance parameters based on blinded data from
      the ongoing trial, and allows to adjust the sample size based on the acquired
      information. In the present paper, this methodology is developed for clinical
      trials with count data as the primary endpoint. In multiple sclerosis such
      endpoints are commonly used in phase 2 trials (lesion counts in magnetic
      resonance imaging (MRI)) and phase 3 trials (relapse counts). Sample size
      adjustment formulas are presented for both Poisson-distributed data and for
      overdispersed Poisson-distributed data. The latter arise from sometimes
      considerable between-patient heterogeneity, which can be observed in particular
      in MRI lesion counts. The operation characteristics of the procedure are
      evaluated by simulations and recommendations on how to choose the size of the
      internal pilot study are given. The results suggest that blinded sample size
      reestimation for count data maintains the required power without an increase in
      the type I error.

PMID- 20146205
TI  - Prognostic benefit of transcatheter aortic valve implantation compared with
      medical therapy in patients with inoperable aortic stenosis.
AB  - OBJECTIVES: To compare survival in patients with inoperable aortic stenosis who
      undergo transcatheter aortic valve implantation against those managed medically.
      BACKGROUND: Without surgical correction, survival of patients with severe
      symptomatic aortic stenosis is poor. It is unknown whether patients undergoing
      transcatheter aortic valve implantation (TAVI) have a better prognosis than
      similar patients who are treated with medical management. METHODS: Survival rates
      were compared in consecutive patients with severe symptomatic aortic stenosis who
      either underwent TAVI or continued on medical management following
      multidisciplinary team assessment. All patients had been turned down, or
      considered at unacceptably high risk, for conventional aortic valve surgery.
      Patients were reviewed in clinic or by telephone six monthly. Mortality data was
      obtained from the United Kingdom Office of National Statistics. RESULTS: The
      study group included 85 patients aged 81 +/- 7 years (range 62-94), of whom 48
      were male. Thirty eight patients underwent TAVI while 47 patients were deemed
      unsuitable based on echocardiographic, angiographic, or clinical criteria and
      remained on medical therapy. The calculated EuroSCORE for the TAVI group was 11
      +/- 2 and for the medical group 9 +/- 2 (P < 0.001). TAVI-related procedural
      mortality was 2.6%, and 30-day mortality was 5.2%. Among the medically-treated
      patients, 14 (30%) underwent palliative balloon aortic valvuloplasty, with a
      trend toward improved survival (P = 0.06). During overall follow-up of 215 +/-
      115 days there were a total of 18 deaths; TAVI N = 5 (13%); Medical N = 13 (28%)
      (P = 0.04). CONCLUSIONS: Patients with severe aortic valve disease who are not
      suitable for surgical aortic valve replacement have an improved prognosis if
      treated with transcatheter aortic valve implantation rather than continuing on
      medical management alone.

PMID- 20146206
TI  - CT angiography for assessment of intracranial basilar apex aneurysm neck diameter
      reduction poststenting for treatment planning.
AB  - BACKGROUND AND PURPOSE: Once a contraindication for a neuro-interventional
      therapeutic approach, some wide-necked aneurysms can now be treated with stent
      assistance. Radiologically assessing the impact of a stent on the neck of a wide
      neck bifurcation, aneurysm remains a challenge however. METHODS: A 76-year-old
      female with a large irregular basilar apex aneurysm was referred for endovascular
      treatment. Angiographic imaging revealed a basilar apex aneurysm with a 6-mm neck
      and a 14-mm dome. The decision was made to perform staged stent-assisted coiling
      of the aneurysm. In the interim time, although the stent was allowed to heal in
      place, a CTA was done to assess the positioning of the stent and the degree of
      neck narrowing. RESULTS: The CTA showed that the neck had been narrowed from 6 to
      2 mm hence making endovascular coiling feasible. CONCLUSION: Our case illustrates
      the use of CTA poststent deployment to visualize the change in aneurysm neck
      caliber precoil embolization.

PMID- 20146207
TI  - Transcatheter closure of large congenital coronary-cameral fistulae with
      Amplatzer devices.
AB  - OBJECTIVES: To report on the methods and results of treatment of large congenital
      coronary-cameral fistulae by transcatheter closure with Amplatzer devices.
      BACKGROUND: Large coronary-cameral fistulae cause a steal phenomenon from the
      normal coronary circulation. Surgical closure is an option. However,
      transcatheter methods allow for temporary occlusion, definition of anatomy, and
      online assessment of successful closure. Amplatzer devices are compact occluders
      that can be fully delivered, collapsed, and repositioned until a satisfactory
      position is attained. METHODS: Coronary and fistula anatomy were defined by
      selective coronary angiography with or without temporary occlusion. Device
      closure of the fistula was performed at the most distal point accessible, often
      from the cameral side using an arteriovenous loop method. RESULTS: Ten patients
      of median age 2.6 years (0.5-52.2) and weight 14.4 kg (6.1-67) underwent an
      attempt at transcatheter closure of a large fistula. In nine patients, the
      fistula was closed successfully with a device. There were no complications.
      CONCLUSIONS: Transcatheter closure of coronary-cameral fistula with Amplatzer
      devices is safe and effective.

PMID- 20146208
TI  - Atrioventricular block after transcatheter ASD closure using the Amplatzer septal
      occluder: risk factors and recommendations.
AB  - Transcatheter device closure of atrial septal defects is now considered an
      alternative option to open heart surgery with good short-term and long-term
      results (Du et al., J Am Coll Cardiol 2002;39:1836-1844, Chessa et al., J Am Coll
      Cardiol 2002;39:1061-1065); in comparison with surgical closure, the complication
      rate is lower (Du et al., J Am Coll Cardiol 2002;39:1836-1844). Arrhythmias are
      known infrequent complications of device closure. However, complete heart block
      is a rare complication of both treatment modalities (Chessa et al., J Am Coll
      Cardiol 2002;39:1061-1065). We report two patients who developed atrioventricular
      (AV) block within 48 hr after uncomplicated device closure of ASD using the
      Amplatzer septal occluder (ASO) device. Despite trials of high dose steroids and
      non-steroidal anti-inflammatory agents in both patients, the response was
      inadequate and by the end of the first week, both patients were ultimately sent
      for surgical removal of their devices with complete resolution of their
      atrioventricular conduction abnormalities. We discuss the possible etiology and
      risk factors of AV block and propose recommendations for management of such a
      complication.

PMID- 20146209
TI  - A novel technique for ultra-low contrast administration during angiography or
      intervention.
AB  - Contrast-induced nephropathy (CIN) after coronary angiography or intervention is
      associated with substantial morbidity. The data supporting various prophylactic
      measures and adjunctive therapies to prevent this complication are conflicting.
      However, contrast volume is clearly related to CIN after percutaneous coronary
      intervention (PCI), and the risk of CIN has been shown to be directly related to
      contrast dose. Therefore, minimizing contrast exposure is a primary method to
      reduce the risk of CIN, especially in at-risk patients. We report a novel
      technique designed to deliver ultra-low (<15 cm(3)) volume contrast to patients
      with chronic kidney disease undergoing coronary angiography and PCI.

PMID- 20146210
TI  - Synthesis and characterization of enzymatically degradable PEG-based peptide
      containing hydrogels.
AB  - Biodegradable hydrogels were synthesized by the click reaction of 4-arm azido
      terminated PEG differing in molecular weight (2,100 and 8,800) and two alkyne
      terminated peptides: [alkyne]-GFLGK-[alkyne] and ([alkyne]-GFLG)(2)K. The
      physical properties of in situ formed hydrogels were examined. The hydrogels were
      highly elastic as determined by rheological and microrheological studies.
      Swelling degree and enzymatic degradation by papain were dependent on the
      molecular weight of the PEG, but not the peptide. For PEG8800-based hydrogels,
      time-course analysis of degradation showed that the molecular weight of the
      soluble fraction quickly reached the PEG precursor value. These findings may
      guide future design of hydrogels with controllable mechanical properties and
      enzymatic degradability.

PMID- 20146211
TI  - Toward a bioartificial pancreas: diffusion of insulin and IgG across
      immunoprotective membranes with controlled hydrophilic channel diameters.
AB  - Research continued toward a bioartificial pancreas (BAP). Our BAPs consist of a
      perforated nitinol scaffold coated with reinforced amphiphilic conetwork
      membranes and contain live pancreatic islets. The membranes are assemblages of
      cocontinuous hydrophobic domains and hydrophilic channels whose diameters were
      varied by the MW of hydrophilic segments between crosslinks (M(c,HI) = 32, 44,
      and 74 kg x mol(-1)). We studied the diffusion rate of insulin, BSA, and IgG
      across the membrane of the BAP in the absence of islets. Membranes of M(c,HI) =
      74 kg x mol(-1) showed rapid insulin and BSA transport and negligible IgG
      diffusion. BAPs containing approximately 300 mouse islets showed appropriate
      response upon glucose challenge in vitro. The BAP implanted into diabetic mice
      reduced hyperglycemia and maintained islet viability for at least 4 d.

PMID- 20146213
TI  - Is prenatal volumetric evaluation of aneurysm of the vein of Galen important in
      the prediction of adverse fetal outcome?
AB  - Aneurysm of the vein of Galen is a rare congenital vascular malformation of the
      central nervous system. There are controversies in the literature regarding the
      possible prognostic value of aneurysmal volume estimation with 3-dimensional US
      for the prediction of fetal outcome. In this report, we present a case of
      prenatally diagnosed large aneurysm of the vein of Galen complicated by heart
      failure in a fetus. The volume of the malformation was calculated as 17.8 cm(3)
      and the fetal outcome was poor.

PMID- 20146214
TI  - Can contrast-enhanced sonography distinguish benign from malignant breast masses?
AB  - BACKGROUND: We investigated whether microvascular enhancement on contrast
      enhanced sonographic (CEUS) imaging can aid in distinguishing between benign and
      malignant lesions and correlated these findings with histopathological findings.
      METHOD: Fifteen patients with a palpable breast mass were recruited. Following
      informed consent, 4.8 mL of the microbubble contrast agent SonoVue was injected
      intravenously. Digital video clips of lesion enhancement were obtained and
      reviewed by a consultant radiologist who scored each lesion on the following
      characteristics: homogeneous versus heterogeneous enhancement, the presence or
      absence of focal defects, well- versus ill-defined margins and vascular
      morphology score (VMS). RESULT: Histologically there were 7 malignant and 8
      benign lesions. The calculated sensitivity for CEUS in the diagnosis of
      malignancy was 100%, with a 37.5% specificity. There was no statistically
      significant difference in overall mean VMS between the malignant and benign
      lesions. CONCLUSION: The results of our study have not shown any additional
      benefit in the use of CEUS over conventional triple assessment. The positive
      trend seen in the higher mean VMS for the malignant tumors needs further
      investigation with a larger cohort of patients.

PMID- 20146215
TI  - The challenges of high-dose chemotherapy in CNS tumors.
AB  - High-dose, myeloablative chemotherapy with hematopoietic stem cell rescue is used
      in children and young adults with brain tumors for which conventional therapy is
      either excessively toxic (e.g., radiotherapy in infants) or ineffective. Thus,
      the aims of such strategies are to improve both quantity and quality of life.
      Whether high-dose chemotherapy is less neurotoxic and more effective than other
      therapeutic approaches is still controversial. We will consider the difficulties
      in analyzing published data and the challenges of designing effective clinical
      trials that test high-dose chemotherapy in patients with brain tumors.

PMID- 20146216
TI  - Biological modification strategies following marrow ablative, high-dose
      chemotherapy (HDCT) with autologous hematopoietic stem cell rescue (AHSCR) for
      pediatric brain tumors.
AB  - Maintenance biology-based therapy following HDCT/AHSCR in pediatric brain tumors
      has not been tested as yet. Failure of the HDCT/AHSCR might be due to tumor
      immunity dysregulation, reactivation of the angiogenic switch and other
      mechanisms. Angiogenesis has been shown to be reactivated following chemotherapy.
      The angiogenic factors engaged in this process in childhood brain tumors
      following HDCT/AHSCR have not been tested in the clinic. Metronomic chemotherapy
      has been found to be safe and angiogenesis inhibitors are currently tested in
      children. Other good possible candidates for clinical trials in this setting
      include retinoic acid and immunotherapy.

PMID- 20146217
TI  - Medulloblastoma in young children.
AB  - In early childhood medulloblastoma, three distinct treatment strategies are
      currently used by different national groups to improve survival rates and to
      delay or avoid craniospinal radiotherapy: (1) systemic chemotherapy and high-dose
      chemotherapy, followed by radiotherapy at relapse; (2) systemic and
      intraventricular chemotherapy; (3) systemic chemotherapy and local conformal
      radiotherapy. A role for high-dose chemotherapy to delay or avoid craniospinal
      radiotherapy as a part of multimodal treatment strategies, especially in young
      children with metastatic or postoperative residual disease, has been recognized
      by different co-operative groups. Clinical and histological factors such as
      nodular-desmoplastic variants are considered as important prognostic factors for
      risk-adapted treatment recommendations.

PMID- 20146218
TI  - Non-cerebellar primitive neuroectodermal tumors (PNET): summary of the Milan
      consensus and state of the art workshop on marrow ablative chemotherapy with
      hematopoietic cell rescue for malignant brain tumors of childhood and
      adolescents.
AB  - CNS non-cerebellar primitive neuroectodermal tumors (PNET) represent <5% of all
      childhood brain tumors. Despite similar therapies, these patients have had
      significantly worse outcomes compared to patients with medulloblastoma. Although
      these tumors have historically been considered analogous to medulloblastoma,
      there is growing evidence that they are biologically distinct. Since these tumors
      are relatively rare, there are few large series in the literature. Here we
      present the international experience treating these patients with a variety of
      therapies, including marrow ablative chemotherapy followed by autologous
      hematopoietic cell rescue.

PMID- 20146219
TI  - Is there a role for myeloablative chemotherapy with autologous hematopoietic cell
      rescue in the management of childhood high-grade astrocytomas?
AB  - High-grade or malignant glioma represent 10% of pediatric brain tumors and are,
      taken as a whole, the second more frequent malignant histotype after
      medulloblastoma. Apart from a complete excision followed by full dose local
      radiotherapy, chemotherapy seems to give some beneficial to final outcome.
      Different trials have explored the role of high-dose chemotherapy that
      theoretically could give an advantage to these patients by overcoming blood-brain
      barrier, tumor cell chemo-resistance and inducing a wider number of responses. It
      is, however, still doubtful if better responses translate into improved outcome
      and which patients can have a true beneficial from this treatment strategy.

PMID- 20146220
TI  - The role of myeloablative chemotherapy with autologous hematopoietic cell rescue
      in central nervous system germ cell tumors.
AB  - This review of the experience of high dose chemotherapy in patients with
      recurrent or refractory intracranial germ cell tumor confirms that sustained
      tumor control can be achieved with this modality both in germinoma and non
      germinomatous germ cell tumors. Data from cooperative groups in Europe and North
      America suggest that the success rate is higher among patients with recurrent
      germinoma. The role of adjuvant radiation in that context remains unclear. These
      promising results have led some cooperative groups to incorporate in their
      protocols a high dose chemotherapy component for newly diagnosed patients with
      high-risk features or poor response to initial chemotherapy.

PMID- 20146221
TI  - A consensus and state-of-the-art workshop: marrow ablative chemotherapy with
      hematopoietic cell rescue for malignant brain tumors of childhood and
      adolescence.

PMID- 20146222
TI  - Role of high-dose chemotherapy (HDCT) in treatment of atypical teratoid/rhabdoid
      tumors (AT/RTs).
AB  - Atypical teratoid/rhabdoid tumors (AT/RTs) of the CNS have been recently
      characterized as a distinct clinicopathologic entity with an unusually poor
      prognosis and with the highest incidence in the first 2 years of life. It often
      arises in the posterior fossa and its distinctive immunohistochemical (negative
      stain for INI-1) and cytogenetic features (monosomy or deletion of chromosome 22)
      permit an adequate diagnosis in most of cases. AT/RT of the CNS is a usually
      fatal disease virtually unresponsive to chemotherapy (CT) and radiotherapy (RT).
      Rapid progression and CNS dissemination are commonly reported. Whether combined
      regimens including high-dose CT are able to prolong survival or change the
      natural history of this tumor are under evaluation.

PMID- 20146223
TI  - Role of high-dose chemotherapy for recurrent medulloblastoma and other CNS
      primitive neuroectodermal tumors.
AB  - We summarize data presented on the use of high-dose chemotherapy (HDCT) with stem
      cell rescue for patients with recurrent medulloblastoma and other primitive
      neuroectodermal tumors as presented at an international consensus and state of
      the art workshop held in Milan in 2006. Eight, mainly institutional, studies were
      presented that included 159 patients who received HDCT of whom 22% were disease
      free survivors at the time of reporting. Of those receiving HDCT and who relapsed
      having received previous radiotherapy, 17.3% were disease-free survivors at the
      time of reporting. However, from the two national studies that reported results
      from the time of relapse, only 4.2% were event free survivors. The outlook for
      previously irradiated patients with recurrent PNETs remains extremely poor and
      more effective therapeutic approaches are needed.

PMID- 20146226
TI  - High-resolution spiral imaging on a whole-body 7T scanner with minimized image
      blurring.
AB  - High-resolution (approximately 0.22 mm) images are preferably acquired on whole
      body 7T scanners to visualize minianatomic structures in human brain. They
      usually need long acquisition time ( approximately 12 min) in three-dimensional
      scans, even with both parallel imaging and partial Fourier samplings. The
      combined use of both fast imaging techniques, however, leads to occasionally
      visible undersampling artifacts. Spiral imaging has an advantage in acquisition
      efficiency over rectangular sampling, but its implementations are limited due to
      image blurring caused by a strong off-resonance effect at 7T. This study proposes
      a solution for minimizing image blurring while keeping spiral efficient. Image
      blurring at 7T was, first, quantitatively investigated using computer simulations
      and point-spread functions. A combined use of multishot spirals and ultrashort
      echo time acquisitions was then employed to minimize off-resonance-induced image
      blurring. Experiments on phantoms and healthy subjects were performed on a whole
      body 7T scanner to show the performance of the proposed method. The three
      dimensional brain images of human subjects were obtained at echo time = 1.18 ms,
      resolution = 0.22 mm (field of view = 220 mm, matrix size = 1024), and in-plane
      spiral shots = 128, using a home-developed ultrashort echo time sequence
      (acquisition-weighted stack of spirals). The total acquisition time for 60
      partitions at pulse repetition time = 100 ms was 12.8 min without use of parallel
      imaging and partial Fourier sampling. The blurring in these spiral images was
      minimized to a level comparable to that in gradient-echo images with rectangular
      acquisitions, while the spiral acquisition efficiency was maintained at eight.
      These images showed that spiral imaging at 7T was feasible.

PMID- 20146224
TI  - Laser desorption postionization for imaging MS of biological material.
AB  - Vacuum ultraviolet single photon ionization (VUV SPI) is a soft ionization
      technique that has the potential to address many of the limitations of matrix
      assisted laser desorption/ionization (MALDI) for imaging MS. Laser desorption
      postionization (LDPI) uses VUV SPI for postionization and is experimentally
      analogous to a MALDI instrument with the addition of a pulsed VUV light source.
      This review discusses progress in LDPI-MS over the last decade, with an emphasis
      on imaging MS of bacterial biofilms, analytes whose high salt environment make
      them particularly resistant to imaging by MALDI-MS. This review first considers
      fundamental aspects of VUV SPI including ionization mechanisms, cross sections,
      quantum yields of ionization, dissociation and potential mass limits. The most
      common sources of pulsed VUV radiation are then described along with a newly
      constructed LDPI-MS instrument with imaging capabilities. Next, the detection and
      imaging of small molecules within intact biofilms is demonstrated by LDPI-MS
      using 7.87 eV (157.6 nm) VUV photons from a molecular fluorine excimer laser,
      followed by the use of aromatic tags for detection of selected species within the
      biofilm. The final section considers the future prospects for imaging intact
      biological samples by LDPI-MS.

PMID- 20146227
TI  - Spatial patterns of cartilage loss in the medial femoral condyle in
      osteoarthritic knees: data from the Osteoarthritis Initiative.
AB  - The objective of this study was to develop a technique for analyzing spatial
      patterns of cartilage loss in the medial femoral condyle (MF), and to study MF
      cartilage loss in participants of the Osteoarthritis Initiative. Using a 0.7 mm
      sagittal double echo at steady state (DESS) sequence, 160 osteoarthritic knees
      from 80 participants with varying degrees of medial joint space narrowing were
      imaged at baseline and 1-year follow-up. MF cartilage was segmented and cartilage
      loss determined. Rate of change varied significantly (P = 0.0067) along the
      anterior-posterior extension of the MF, with the greatest changes (-45 microm, 
      2.7%) observed 30-60 degrees posterior to the trochlear notch. The rate was
      greater in the central MF after excluding peripheral aspects of the MF from
      analysis. Sensitivity to change was greatest at 45-75 degrees (standardized
      response mean = -0.32) but was minimally affected by medial-lateral trimming. In
      conclusion, the greatest sensitivity to change was achieved when analyzing the
      posterior aspect of the central, weight-bearing MF.

PMID- 20146229
TI  - Evidence for weak protein binding of commercial extracellular gadolinium contrast
      agents.
AB  - It is widely assumed that commercial extracellular gadolinium-based contrast
      agents do not bind to proteins. Here, nuclear magnetic relaxation dispersion was
      used to characterize the interaction between the contrast agents gadodiamide and
      gadopentetate dimeglumine and the proteins human serum albumin, chicken egg white
      lysozyme, egg white proteins, or milk proteins. In all cases, contrast agent
      relaxivity was increased at all field strengths measured (0.0002 to 1.4 T) when
      protein was added. A distinct peak in relaxivity was observed between 0.5 and 0.7
      T that is consistent with fractional protein binding and that could not be
      attributed to changes in solution viscosity. This peak was observed for
      gadodiamide with all four protein solutions and for gadopentetate dimeglumine
      with lysozyme, human serum albumin, and milk proteins. Protein binding was both
      contrast agent and protein dependent. For gadodiamide, the highest affinity was
      to egg white and milk proteins, while gadopentetate dimeglumine interacted most
      strongly with lysozyme. Protein binding was estimated at 30-40% for a 0.7 mmol/kg
      solution of gadodiamide in egg white or milk proteins. These results have
      implications for the accurate determination of contrast agent concentration in
      vivo. Weak protein binding may be an additional discriminating factor in
      understanding differences in the toxicokinetics of contrast agents.

PMID- 20146228
TI  - Effects of CBV, CBF, and blood-brain barrier permeability on accuracy of PASL and
      VASO measurement.
AB  - Cerebral blood flow, cerebral blood volume (CBV), and water permeability through
      blood-brain barrier are important hemodynamic parameters in brain physiology.
      Pulsed arterial spin labeling and vascular-space occupancy techniques have been
      used to measure regional cerebral blood flow and CBV, respectively. However,
      these techniques generally ignore the effects of one hemodynamic parameter on the
      measurement of others. For instance, the influences of CBV changes on arterial
      spin labeling or the permeability effects on vascular-space occupancy typically
      were not accounted for in the quantification of blood flow or volume. In the
      current work, the biophysical effects of CBV on pulsed arterial spin labeling and
      permeability on vascular-space occupancy signals are evaluated using a general
      two-compartment model. The dependence of these effects on the T(1) at various
      field strengths is also assessed by simulations. Results indicate that CBV has
      negligible to small influences on pulsed arterial spin labeling signal (<6.6% at
      3 T) and permeability effects are negligible on vascular-space occupancy signal
      (<0.1% at 3 T) under normal physiologic conditions. In addition, CBV effect on
      pulsed arterial spin labeling is further diminished at high field strengths, but
      residual blood contamination in vascular-space occupancy signal may be enhanced
      at high fields due to the reduced difference between extra- and intravascular
      T(1) values.

PMID- 20146230
TI  - Antihyperlipidemic activity of 3-hydroxymethyl xylitol, a novel antidiabetic
      compound isolated from Casearia esculenta (Roxb.) root, in streptozotocin
      diabetic rats.
AB  - Casearia esculenta root (Roxb.) is widely used in traditional system of medicine
      to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX),
      has been isolated, and its optimum dose has been determined in a short duration
      study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic
      rats on carbohydrate metabolism was investigated, and its antihyperglycemic
      effect was shown previously (Chandramohan et al., Eur J Pharmacol 2008;590:437
      443). In this study we investigated the effect of 3-HMX on plasma and tissue
      lipid profiles in streptozotocin-induced diabetic rats. Diabetes was induced in
      adult male albino rats of the Wistar strain, weighing 180-200 g, by
      administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. The
      normal and diabetic rats were treated with 3-HMX (40 mg/kg BW/day) for 45 days.
      The levels of total cholesterol, triglycerides, free fatty acids, and
      phospholipids were assayed in the plasma besides lipoprotein-cholesterol (high
      density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL
      C), and very low density lipoprotein-cholesterol (VLDL-C)) and tissues (liver,
      kidney, heart, and brain). Total cholesterol, triglyceride, free fatty acid, and
      phospholipid (LDL-C and VLDL-C in plasma only) levels increased in plasma and
      tissues significantly, whereas plasma HDL-C significantly decreased in diabetic
      rats. Treatment with 3-HMX or glibenclamide reversed the above-mentioned changes
      and improved toward normalcy. Histological study of liver also confirmed the
      biochemical findings. Thus administration of 3-HMX is able to reduce
      hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus.

PMID- 20146231
TI  - Novel membrane-permeable contrast agent for brain tumor detection by MRI.
AB  - One of the key challenges hindering the clinical intervention against brain
      cancer is defined by the inability to detect brain tumors at an early enough
      stage to permit effective therapy. Furthermore, the rapid growth and severe
      lethality of this form of cancer predicate the vital importance of monitoring the
      development of the pathology and its outcome after therapeutic intervention. With
      this in mind, we designed a novel membrane-permeant contrast agent, MN-MPAP
      Cy5.5, which consists of a superparamagnetic iron oxide core, for MRI conjugated
      to myristoylated polyarginine peptides, as a membrane translocation module and
      labeled with the near-infrared dye Cy5.5 for correlative microscopy. This probe
      showed a remarkable uptake by U-87 human glioma cells in vitro and localized and
      delineated stereotactically injected tumor in vivo by MRI. Our findings suggest
      that the agent mediates its effects by translocation of the magnetic
      nanoparticles label across the leaky tumor vasculature, followed by enhanced
      accumulation in tumor cells. The noninvasive detection of brain tumors when they
      are still small represents a formidable challenge from an imaging standpoint. Our
      study describes an improved strategy to detect brain lesions by utilizing a
      contrast agent with membrane translocation properties.

PMID- 20146232
TI  - Quantitative magnetization transfer and myelin water imaging of the evolution of
      acute multiple sclerosis lesions.
AB  - Quantitative magnetization transfer imaging provides in vivo estimates of liquid
      and semisolid constituents of tissue, while estimates of the liquid
      subpopulations, including myelin water, can be obtained from multicomponent T(2)
      analysis. Both methods have been suggested to provide improved myelin specificity
      compared to conventional MRI. The goal of this study was to investigate the
      sensitivity of each technique to the progression of acute, gadolinium-enhancing
      regions of multiple sclerosis. Magnetization transfer and T(2) relaxometry data
      were acquired longitudinally over the course of 1 year in five relapsing
      remitting multiple sclerosis patients and in five healthy controls. Parametric
      maps were analyzed in enhancing lesions and normal-appearing white matter
      regions. Quantitative magnetization transfer parameters in lesions were most
      abnormal at the time of enhancement and followed a pattern of recovery over
      subsequent months. Lesion myelin water fraction was abnormal but did not show a
      significant trend over time. Quantitative magnetization transfer was able to
      track the degree and timing of the partial recovery in enhancing multiple
      sclerosis lesions in a small group of patients, while the recovery was not
      detected in myelin water estimates, possibly due to their large variability. Our
      data suggest the recovery is characterized by quick resolution of inflammation
      and a slower remyelination process.

PMID- 20146233
TI  - Assessment of arterial arrival times derived from multiple inversion time pulsed
      arterial spin labeling MRI.
AB  - The purpose of this study was to establish a normal range for the arterial
      arrival time (AAT) in whole-brain pulsed arterial spin labeling (PASL) cerebral
      perfusion MRI. Healthy volunteers (N = 36, range: 20 to 35 years) provided
      informed consent to participate in this study. AAT was assessed in multiple brain
      regions, using three-dimensional gradient and spin echo (GRASE) pulsed arterial
      spin labeling at 3.0 T, and found to be 641 +/- 95, 804 +/- 91, 802 +/- 126, and
      935 +/- 108 ms in the temporal, parietal, frontal, and occipital lobes,
      respectively. Mean gray matter AAT was found to be 694 +/- 89 ms for females (N =
      15), which was significantly shorter than for men, 814 +/- 192 ms (N = 21; P <
      0.0003), and significant after correcting for brain volume (P < 0.001).
      Significant AAT sex differences were also found using voxelwise permutation
      testing. An atlas of AAT values across the healthy brain is presented here and
      may be useful for future experiments that aim to quantify cerebral blood flow
      from ASL data, as well as for clinical comparisons where disease pathology may
      lead to altered AAT. Pulsed arterial spin labeling signals were simulated using
      an identical sampling scheme as the empiric study and revealed AAT can be
      estimated robustly when simulated arrival times are well beyond the normal range.

PMID- 20146234
TI  - lacZ as a genetic reporter for real-time MRI.
AB  - Molecular imaging based on MRI is currently hampered by the lack of genetic
      reporters for in vivo imaging. We determined that the commercially available
      substrate S-Gal can be used to detect genetically engineered beta-galactosidase
      expressing cells by MRI. The effect and specificity of the reaction between beta
      galactosidase and S-Gal on MRI contrast were determined both in vitro and in
      vivo. beta-galactosidase activity in the presence of S-Gal resulted in enhanced
      T(2) and T*(2) MR-contrast, which was amplified with increasing magnetic field
      strengths (4.7-17.6 T) in phantom studies. Using both lacZ(+) transgenic animals
      and lacZ(+) tissue transplants, we were able to detect labeled cells in live
      animals in real time. Similar to phantom studies, detection of the labeled
      cells/tissues in vivo was enhanced at high magnetic fields. These results
      demonstrate that the genetic reporter, lacZ, can be used as an in vivo marker
      gene using high-field-strength MRI.

PMID- 20146236
TI  - Eigenmode analysis of transmit coil array for tailored B1 mapping.
AB  - In vivo radiofrequency (RF) field B(1) mapping represents an essential
      prerequisite for parallel transmit applications. However, the large dynamic range
      of the transmit fields of the individual coil elements challenges the accuracy of
      MR-based B(1) mapping techniques. In the present work, the B(1) mapping error and
      its impact on the RF performance are studied based on a coil eigenmode analysis.
      Furthermore, the linear properties of the transmit chain are exploited to
      virtually adjust the weighting of the different coil eigenmodes in the B(1)
      mapping procedure, resulting in considerably reduced mapping errors. In addition,
      the weighting of the eigenmodes is tailored to potential target applications,
      e.g., specific absorption rate (SAR) reduced RF shimming or multidimensional RF
      pulses, resulting in improved RF performance. The basic theoretic principles of
      the concept are elaborated and validated by corresponding simulations.
      Furthermore, results on B(1) mapping and RF shimming experiments, performed on
      phantoms and in vivo using a 3-T scanner equipped with an eight-channel
      transmit/receive body coil, are presented to prove the feasibility of the
      approach.

PMID- 20146235
TI  - Fat-free MRI based on magnetization exchange.
AB  - An MRI technique is proposed for complete fat signal elimination. This approach
      exploits the fact that water rapidly exchanges magnetization with protons in
      protein and membrane phospholipid of tissue and cells but does not exchange
      magnetization with triglyceride or fat protons in the tissue. Saturation of the
      proton signal from protein and membrane phospholipid thus results in partial
      saturation of the water proton signal, allowing acquisition of an image including
      a portion of the water signal and the full fat signal. Subtraction of this image
      from the standard image, containing both water and fat signals, results in an
      image in which all fat signal is cancelled. This fat-free image is sensitive to
      magnetization transfer and to water density and relaxation time, providing the
      possibility of additional contrast. Unlike most fat suppression techniques, this
      method is not compromised by the static or radiofrequency field heterogeneity and
      is equally efficient for all fat resonances independent of their chemical shift
      frequency.

PMID- 20146237
TI  - Fecal bacterial diversity of human-habituated wild chimpanzees (Pan troglodytes
      schweinfurthii) at Mahale Mountains National Park, Western Tanzania.
AB  - Although the intestinal flora of chimpanzees has not been studied, insight into
      this dynamic environment can be obtained through studies on their feces. We
      analyzed fecal samples from human-habituated, wild chimpanzees at Mahale
      Mountains National Park, Tanzania, and compared microbial community profiles to
      determine if members of the same social group were similar. Between July and
      December 2007, we collected fresh fecal samples from 12 individuals: four
      juveniles, four adolescents, and four adults, including three parent-offspring
      pairs. Each sample was analyzed using Terminal-Restriction Fragment Length
      Polymorphism of amplified 16S rRNA genes. Twelve different profiles were
      generated, having between 1 and 15 Terminal-Restriction Fragments (T-RFs).
      Overall, a total of 23 different T-RFs were produced. Putative assignments of T
      RFs corresponded to the phyla Firmicutes (Clostridia, Bacilli, and Lactobacilli),
      Bacteroidetes, Tenericutes (Mollicutes Class), Actinobacteria, and
      Proteobacteria, as well as to uncultured or unidentified organisms. Firmicutes
      and Bacteroidetes phyla and Mollicutes Class were the most commonly assigned in
      11, 8, and 8 of the samples, respectively, with this being the first report of
      Mollicutes in wild chimpanzees. Principal Components Analysis (PCA) revealed
      clustering of nine samples, and 80.5% of the diversity was accounted for by three
      samples. Morisita indices of community similarity ranged between 0.00 and 0.89,
      with dissimiliarity (<0.5) between most samples when compared two at a time. Our
      findings suggest that, although phylotypes are common among individuals, profiles
      among members of the same social group are host-specific. We conclude that
      factors other than social group, such as kinship and age, may influence fecal
      bacterial profiles of wild chimpanzees, and recommend that additional studies be
      conducted.

PMID- 20146238
TI  - Confiding in those better than ourselves: stroke research and clinical practice,
      are we asking the right questions?

PMID- 20146239
TI  - The craniocervical flexion test: intra-tester reliability in asymptomatic
      subjects.
AB  - BACKGROUND AND PURPOSE: The deep neck flexor muscles (DNFs) stabilize the
      cervical spine and cervicogenic pain appears to adversely affect their endurance
      capacity. They are inaccessible to direct palpation, thereby making assessment
      difficult. However, the cranio-cervical flexion test (CCFT) provides an indirect
      method of assessing the endurance capacity of the DNFs. The purpose of the
      present study was to evaluate the intratester reliability of the CCFT in
      asymptomatic subjects. METHOD: The clinical protocol of the CCFT was measured on
      two occasions with 7 days between measurements. Prior to testing, participants
      were trained and compensation strategies were corrected. Nineteen asymptomatic
      participants (mean age 24.9 years; range 22-36) were recruited. RESULTS: The test
      had excellent intratester reliability (intraclass correlation coefficient =
      0.983; standard error of the mean = 8.94; smallest real difference = 24.7). A
      Bland and Altman's limits of agreement analysis confirmed the high reliability of
      the test. CONCLUSION: The CCFT results demonstrated excellent intra-tester
      reliability in asymptomatic subjects, thus contributing to the normative data
      regarding the test.

PMID- 20146240
TI  - A copula-based mixed Poisson model for bivariate recurrent events under event
      dependent censoring.
AB  - In many chronic disease processes subjects are at risk of two or more types of
      events. We describe a bivariate mixed Poisson model in which a copula function is
      used to model the association between two gamma distributed random effects. The
      resulting model is a bivariate negative binomial process in which each type of
      event arises from a negative binomial process. Methods for parameter estimation
      are described for parametric and semiparametric models based on an EM algorithm.
      We also consider the issue of event-dependent censoring based on one type of
      event, which arises when one event is sufficiently serious that its occurence may
      influence the decision of whether to withdraw a patient from a study. The
      asymptotic biases of estimators of rate and mean functions from naive marginal
      analyses are discussed, as well as associated treatment effects. Because the
      joint model is fit based on a likelihood, consistent estimates are obtained.
      Simulation studies are carried out to evaluate the empirical performance of the
      proposed estimators with independent and event-dependent censoring and
      applications to a trial of breast cancer patients with skeletal metastases and a
      study of patients with chronic obstructive pulmonary disease illustrate the
      approach.

PMID- 20146241
TI  - Lung adenocarcinoma cells floating in lymphatic vessels resist anoikis by
      expressing phosphorylated Src.
AB  - The ability to resist anoikis is critical for carcinoma cells to metastasize.
      Although several lung adenocarcinoma cell lines were shown to repress anoikis
      through the activation of Src, it remains unknown whether Src actually plays a
      crucial role in anoikis resistance in lung adenocarcinoma tissues. We examined 20
      human lung adenocarcinoma tissues with lymphatic permeation and nine cell lines
      to investigate whether intralymphatic floating carcinoma cells in the tissues,
      used as an in vivo model of anoikis resistance, actually suppressed anoikis and
      whether cell lines in suspension culture, an in vitro model of anoikis
      resistance, survived through Src activation. We observed that the intralymphatic
      carcinoma cells aggregated tightly to form nests expressing E-cadherin and
      phosphorylated Src (p-Src). The apoptotic indices of these cells were comparable
      to those of extracellular matrix adhesive cells in all tissues, indicating that
      the intralymphatic cells actually evaded anoikis. Next, we found that the nine
      cell lines in suspension aggregated loosely (five cell lines) or tightly (four
      cell lines), and all cells resisted anoikis. Upon detachment, four cell lines (LC
      KJ, HCC827, H1650, and H1975) formed compact spheroids that expressed E-cadherin
      and p-Src. The spheroids were similar to intralymphatic tumour nests and were
      thus considered to be a suitable model of the nests. The spheroids of the four
      cell lines underwent apoptosis after treatment with the Src/Abl/Kit inhibitor PP1
      or Src/Abl inhibitor bosutinib. On the other hand, the Abl/Kit inhibitor imatinib
      did not affect cell growth or apoptosis in the four types of spheroids. These
      results indicate that Src, but not Abl or Kit, plays an essential role in the
      development of anoikis resistance in lung adenocarcinomas.

PMID- 20146243
TI  - The correlation structure of longitudinal measurements of vision in patients with
      macular degeneration.
AB  - BACKGROUND: In age-related macular degeneration (ARMD) trials, the FDA-approved
      endpoint is the loss (or gain) of at least three lines of vision as compared to
      baseline. The use of such a response endpoint entails a potentially severe loss
      of information. A more efficient strategy could be obtained by using longitudinal
      measures of the change in visual acuity. In this paper we investigate, by using
      data from two randomized clinical trials, the mean and variance-covariance
      structures of the longitudinal measurements of the change in visual acuity.
      METHODS: Individual patient data were collected in 234 patients in a randomized
      trial comparing interferon-alpha with placebo and in 1181 patients in a
      randomized trial comparing three active doses of pegaptanib with sham. A linear
      model for longitudinal data was used to analyze the repeated measurements of the
      change in visual acuity. RESULTS: For both trials, the data were adequately
      summarized by a model that assumed a quadratic trend for the mean change in
      visual acuity over time, a power variance function, and an antedependence
      correlation structure. The power variance function was remarkably similar for the
      two datasets and involved the square root of the measurement time. CONCLUSIONS:
      The similarity of the estimated variance functions and correlation structures for
      both datasets indicates that these aspects may be a genuine feature of the
      measurements of changes in visual acuity in patients with ARMD. The feature can
      be used in the planning and analysis of trials that use visual acuity as the
      clinical endpoint of interest.

PMID- 20146242
TI  - Adverse drug reactions induced by cardiovascular drugs in cardiovascular care
      unit patients.
AB  - PURPOSE: To detect the type, rate, seriousness, and preventability of adverse
      drug reactions (ADRs) attributable to cardiovascular drugs in cardiovascular care
      unit; and to determine the relationship between patient factors and detected
      ADRs. METHODS: Patients admitted to cardiovascular care units in Tehran Heart
      Center over an eight month period who received at least one cardiovascular drug
      were eligible to enter the study. ADRs were recorded based on information
      collected by interviewing patients, reviewing patients' charts, laboratory test
      monitoring, and confirmation by physicians. The World Health Organization
      definition for ADR, its seriousness and casualty criteria, was used to evaluate
      the reactions. The preventability was estimated based on Schumock and Thornton
      questioning. The relationship between possible risk factors and ADRs occurrence
      were assessed by statistical analysis. RESULTS: During the study period, 677
      patients entered the study. A total number of 189 ADRs were registered of which
      22.2% were serious. The highest ADR rates were observed with Streptokinase
      (59.3%). The rate of preventable ADRs was 6.9%. Multivariate logistic regression
      analysis showed that patients with lower weight (OR = 0.95, 95%CI: 0.9-0.99) and
      patients with smoking history who had concurrent diseases (OR = 8.72, 95%CI: 1.53
      49.52) had a higher risk of experiencing ADRs. CONCLUSION: The rate of ADRs
      induced by cardiovascular drugs in this study was 24.2%. This study has shown
      that anti-arrhythmic and thrombolytic agents need more attention.

PMID- 20146247
TI  - The oxidative products of methionine as site and content biomarkers for peptide
      oxidation.
AB  - Biomarkers for peptide/protein oxidation under oxidative stress (OS) hold both
      incredible application potential as well as significant challenges. In this
      article, liquid chromatography and mass spectrometry were applied to establish a
      new method for evaluating the oxidation site and degree of peptide oxidized, with
      its oxidative product serving as biomarker. In the three model peptides, peptide
      FMRF (containing a methionine) was prone to undergo oxygen addition under
      UV/H(2)O(2) oxidization, forming a sulfoxide (FM(O)RF) with a stable
      chromatographic peak separate from the model peptides. The oxidation content of
      FMRF, expressed as S(FM(O)RF)/(S(FM(O)RF) + S(FMRF)), is positively correlated
      with oxidation time. Based on sequence analysis of FM(O)RF, the oxidation
      mechanism (site and extent) of FMRF under UV/H(2)O(2) oxidization was explicitly
      clarified. By comparing the specific injury to each model peptide, we found that
      the oxidative products of Met-containing peptides are good biomarkers for OS.
      This research not only expands the range of biomarkers for OS, but also provides
      an efficient and accurate method for evaluating oxidation damage to peptides and
      even proteins.

PMID- 20146249
TI  - Macaques in farms and folklore: exploring the human-nonhuman primate interface in
      Sulawesi, Indonesia.
AB  - The island of Sulawesi is an ecologically diverse and anthropogenically complex
      region in the Indonesian archipelago; it is home to multiple macaque species and
      a key locus of human-nonhuman primate interconnections. Here, we review the
      ethnoprimatology of Sulawesi by exploring two primary domains of the human
      macaque interface: overlapping resource use and cultural perceptions of macaques.
      Crop raiding is the primary form of overlapping resource use. While the raiding
      of cacao plantations predominates in Central and South Sulawesi, subsistence
      crops (e.g., sweet potato and maize) are most vulnerable on Buton, Southeast
      Sulawesi. Despite this overlap levels of conflict are generally low, with farmers
      showing considerable tolerance. This tolerance can be explained by positive
      perceptions of the macaques despite their crop raiding behavior, and the finding
      that in some areas macaques figure prominently in local folklore, hence affording
      them protection. These findings provide some hope for the future management and
      conservation of these endemic macaques.

PMID- 20146248
TI  - Grape seed proanthocyanidin suppression of breast cell carcinogenesis induced by
      chronic exposure to combined 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and
      benzo[a]pyrene.
AB  - Breast cancer is the most common type of cancer among women in northern America
      and northern Europe; dietary prevention is a cost-efficient strategy to reduce
      the risk of this disease. To identify dietary components for the prevention of
      human breast cancer associated with long-term exposure to environmental
      carcinogens, we studied the activity of grape seed proanthocyanidin extract
      (GSPE) in suppression of cellular carcinogenesis induced by repeated exposures to
      low doses of environmental carcinogens. We used combined carcinogens 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), at
      picomolar concentrations, to repeatedly treat noncancerous, human breast
      epithelial MCF10A cells to induce cellular acquisition of cancer-related
      properties of reduced dependence on growth factors, anchorage-independent growth,
      and acinar-conformational disruption. Using these properties as biological target
      endpoints, we verified the ability of GSPE to suppress combined NNK- and B[a]P
      induced precancerous cellular carcinogenesis and identified the minimal,
      noncytotoxic concentration of GSPE required for suppressing precancerous cellular
      carcinogenesis. We also identified that hydroxysteroid-11-beta-dehydrogenase 2
      (HSD11B2) may play a role in NNK- and B[a]P-induced precancerous cellular
      carcinogenesis, and its expression may act as a molecular target endpoint in
      GSPE's suppression of precancerous cellular carcinogenesis. And, the ability of
      GSPE to reduce gene expression of cytochrome-P450 enzymes CYP1A1 and CYP1B1,
      which can bioactivate NNK and B[a]P, possibly contributes to the preventive
      mechanism for GSPE in suppression of precancerous cellular carcinogenesis. Our
      model system with biological and molecular target endpoints verified the value of
      GSPE for the prevention of human breast cell carcinogenesis induced by repeated
      exposures to low doses of multiple environmental carcinogens.

PMID- 20146250
TI  - The effect of c-myc on stem cell fate influences skin tumor phenotype.
AB  - Nonmelanoma skin cancers (NMSCs) consist of a variety of tumor types including
      basal cell carcinoma, squamous cell carcinoma, a variety of hair follicle tumors,
      and sebaceous gland tumors. Genetic alterations that alter the fate of
      multipotent stem cells are believed to influence NMSC phenotype. We previously
      generated a transgenic mouse line which constitutively expressed c-myc under the
      control of the K14 promoter (K14.MYC2). These mice exhibited an increase in size
      and number of sebaceous glands, suggesting that c-myc diverted multipotential
      stem cells to a sebaceous lineage. Our goal in the current study was to determine
      if alterations in the commitment of multipotent stem cells to different cell
      fates would influence tumor phenotype. To this end, we exposed K14.MYC2 mice to a
      chemical carcinogenesis protocol and discovered that these mice were predisposed
      to develop sebaceous adenomas. Our data demonstrate that genetic alterations that
      alter the fate of multipotent stem cells during embryonic development can
      markedly influence the phenotype of NMSC that develop following exposure to
      carcinogens.

PMID- 20146252
TI  - Ursolic acid induces PC-3 cell apoptosis via activation of JNK and inhibition of
      Akt pathways in vitro.
AB  - Ursolic acid (UA), a pentacyclic triterpenoid compound, has been demonstrated to
      have an antiproliferative effect in various tumors. We investigated the cell
      killing effects of UA in the human hormone refractory prostate cancer cell line,
      PC-3 cells. Also, the molecular mechanisms underlying its antigrowth effect were
      explored. We found that UA treatment in vitro can effectively inhibit PC-3 cell
      viability in a dose-dependent manner by inducing apoptosis, demonstrated by
      annexin V-FITC/propidium iodide staining. Both extrinsic and intrinsic apoptotic
      pathways appear to be triggered by UA treatment, because inhibiting activation of
      both caspase-8 and -9 could prevent UA-induced apoptosis in PC-3 cells. The c-Jun
      N-terminal kinase (JNK) was found to be activated, followed by Bcl-2
      phosphorylation and activation of caspase-9. On the other hand, UA inhibited the
      Akt pathway, subsequently upregulating the expression of Fas ligand (FasL), which
      initiates death receptor-mediated apoptosis in PC-3 cells. Importantly,
      experimentally lowering FasL expression by siRNA significantly inhibited UA
      induced caspase-8 activation and at least partly attenuated the consequent
      apoptosis, suggesting an involvement of FasL and its regulating pathway in the
      cell killing effect of UA. UA also inhibited cell invasion by downregulating
      matrix metalloproteinase-9 via inhibition of Akt in PC-3 cells. Although further
      evaluation of the UA effects in vivo is needed, the present results suggest the
      potential utility of UA as a novel therapeutic agent in advanced prostate cancer.

PMID- 20146251
TI  - Characterization of harpy/Rca1/emi1 mutants: patterning in the absence of cell
      division.
AB  - We have characterized mutations in the early arrest gene, harpy (hrp), and show
      that they introduce premature stops in the coding region of early mitotic
      inhibitor1 (Rca1/emi1). In harpy mutants, cells stop dividing during early
      gastrulation. Lineage analysis confirms that there is little change in cell
      number after approximately cycle-14. Gross patterning occurs relatively normally,
      and many organ primordia are produced on time but with smaller numbers of cells.
      Despite the lack of cell division, some organ systems continue to increase in
      cell number, suggesting recruitment from surrounding areas. Analysis of
      bromodeoxyuridine incorporation shows that endoreduplication continues in many
      cells well past the first day of development, but cells cease endoreduplication
      once they begin to differentiate and express cell-type markers. Despite
      relatively normal gross patterning, harpy mutants show several defects in
      morphogenesis, cell migration and differentiation resulting directly or
      indirectly from the arrest of cell division.

PMID- 20146253
TI  - AMPK-mediated phosphorylation of murine p27 at T197 promotes binding of 14-3-3
      proteins and increases p27 stability.
AB  - The tuberous sclerosis complex 2 (Tsc2) gene product, tuberin, acts as a negative
      regulator of mTOR signaling, and loss of tuberin function leads to tumors of the
      brain, skin, kidney, heart, and lungs. Previous studies have shown that loss of
      tuberin function affects the stability and subcellular localization of the cyclin
      dependent kinase inhibitor (CKI) p27, although the mechanism(s) by which tuberin
      modulates p27 stability has/have not been elucidated. Previous studies have also
      shown that AMP-activated protein kinase (AMPK), which functions in an energy
      sensing pathway in the cell, becomes activated in the absence of tuberin. Here we
      show that in Tsc2-null tumors and cell lines, AMPK activation correlates with an
      increase in p27 levels, and inhibition of AMPK signaling decreases p27 levels in
      these cells. In addition, activation of AMPK led to phosphorylation of p27 at the
      conserved terminal threonine residue of murine p27 (T197) in both in vitro kinase
      assays and in cells. Phosphorylation of p27 at T197 led to increased interaction
      between p27 and 14-3-3 proteins and increased the protein stability of p27.
      Furthermore, activation of AMPK signaling promoted the interaction between p27
      and 14-3-3 proteins and increased the stability of the p27 protein in a manner
      that was dependent on T197. These data identify a conserved mechanism for the
      regulation of p27 stability via phosphorylation at the terminal threonine
      (mT197/hT198) and binding of 14-3-3 proteins, which when AMPK is activated
      results in stabilization of the p27 protein.

PMID- 20146254
TI  - Sex attractant for the banana moth, Opogona sacchari Bojer (Lepidoptera:
      Tineidae): provisional identification and field evaluation.
AB  - BACKGROUND: The banana moth, Opogona sacchari Bojer, is a polyphagous
      agricultural pest in many tropical areas of the world. The identification of an
      attractant for male O. sacchari could offer new methods for detection, study and
      control. RESULTS: A compound extracted from female O. sacchari elicited responses
      from antennae of male moths. This compound was identified as a 2/3,(Z)13
      octadecadienal by gas chromatography-mass spectrometry. An analog, 2/3,(Z)13
      octadecadienol, was also detected in some extracts at roughly a 1:20 ratio
      (alcohol:aldehyde) but did not elicit responses from antennae of male moths.
      Electroantennograms of synthetic candidate dienals found the strongest responses
      from (Z, Z)-2,13-octadecadienal and (E, Z)-2,13-octadecadienal. In field trials,
      (E, Z)-2,13-octadecadienal attracted more male O. sacchari than (Z, Z)-2,13
      octadecadienal. Attraction was not improved for either of these compounds when
      the corresponding stereoisomeric alcohol was added at ratios of 1:1, 1:10 or
      1:100 (alcohol:aldehyde). Jackson sticky traps containing 250 microg lures of (E,
      Z)-2,13-octadecadienal caught as many males as did traps holding virgin females.
      CONCLUSION: (E, Z)-2,13-octadecadienal has been identified as an attractant for
      O. sacchari males and can be used as a monitoring lure of populations of this
      moth.

PMID- 20146255
TI  - A comparison of OEF and OIF veterans and Vietnam veterans receiving cognitive
      processing therapy.
AB  - The current wars in Iraq and Afghanistan are producing large numbers of veterans
      who have experienced a variety of combat stressors. The potential impact of
      combat exposure has been established, including significant rates of
      posttraumatic stress disorder (PTSD). Limited research has examined potential
      differences between veteran groups and one study to date has examined differences
      between eras in terms of treatment response. The present study seeks to examine
      cohort differences between Operation Enduring Freedom and Operation Iraqi Freedom
      veterans and Vietnam veterans (N = 101) before and after completing treatment for
      PTSD using cognitive processing therapy. Findings suggest that veterans from
      these eras responded differently to treatment and there are multiple variables
      that should be considered in future cohort studies.

PMID- 20146256
TI  - Spinosad resistance development in wild olive fruit fly Bactrocera oleae
      (Diptera: Tephritidae) populations in California.
AB  - BACKGROUND: Among target pests of the insecticide spinosad is the olive fruit
      fly, Bactrocera oleae (Rossi) (Diptera: Tephritidae). In Cyprus, spinosad has
      been sporadically used since its registration in 2002, whereas in Greece its use
      has been very limited since its registration in 2004, particularly in biological
      olive cultivars in Crete. By contrast, in California it has been the only
      insecticide used against the olive fruit fly since its registration in 2004. This
      study aimed at examining the resistance status of the olive fruit fly to
      spinosad. RESULTS: Populations from California, Greece and Cyprus, plus a
      laboratory population, were tested. Bioassays were performed by oral or topical
      application of different concentrations of the insecticide. Cypriot populations
      demonstrated no resistance as compared with that of the laboratory population.
      Among the Greek populations, only one from Crete demonstrated a fourfold increase
      in resistance, whereas five populations from California demonstrated a 9-13-fold
      increase. CONCLUSION: The observed resistance increase was associated with
      spinosad applications in the respective areas. These values are relatively low
      and do not yet pose a serious control problem in the field. However, the observed
      variation documents that spinosad tolerance has increased in areas where the
      insecticide has been more extensively used.

PMID- 20146257
TI  - Social and trauma-related pathways leading to psychological distress and
      functional limitations four years after the humanitarian emergency in Timor
      Leste.
AB  - There is growing acknowledgment that research in the postconflict field needs to
      include a focus on social conditions. The authors applied structural equation
      modeling to epidemiologic data obtained from postconflict Timor-Leste, to examine
      for links involving potentially traumatic events and sociodemographic factors
      (age, gender, educational levels, and unemployment) with psychological symptoms
      and functioning. Exposure to trauma and lack of education emerged as most
      relevant with psychological distress impacting on education in the urban area.
      Age and gender exerted influences at different points in the model consistent
      with the known history of Timor. Although based on cross-sectional data, the
      model supports the relevance of past trauma, posttraumatic distress, and
      postconflict social conditions to functioning in societies such as Timor-Leste.

PMID- 20146258
TI  - Longitudinal mental health screening results among postdeployed U.S. soldiers
      preparing to deploy again.
AB  - Mental health concerns have been documented in soldiers postdeployed from Iraq or
      Afghanistan, but information is limited regarding individuals directed to deploy
      again. Routine screening assessed symptoms of posttraumatic stress disorder,
      depression, anxiety, panic, and hazardous alcohol consumption among 443 soldiers
      after returning from deployment and again before the next deployment. Initial
      rates for meeting screening criteria were under 9% with most around 5%. The
      average number of symptoms reported for depression, anxiety, and alcohol
      consumption decreased from first to second screening, as did the percentage of
      participants who met screening criteria for hazardous alcohol consumption. No
      change was observed on other screening measures. The findings suggest that mental
      health symptoms remain stable or decline for soldiers repeating deployment.

PMID- 20146259
TI  - Molecular analysis of pyrethroid resistance conferred by target insensitivity and
      increased metabolic detoxification in Plutella xylostella.
AB  - BACKGROUND: The pyrethroid resistance of the diamondback moth Plutella xylostella
      (L.) is conferred by increased gene expression of cytochrome P450 to detoxify the
      insecticide and/or through gene mutation of the sodium channel, which makes the
      individual insensitive to pyrethroids. However, no information is available about
      the correlation between the increased metabolic detoxification and the target
      insensitivity in pyrethroid resistance. RESULTS: Frequencies of pyrethroid
      resistant alleles (L1014F, T929I and M918I) and two resistance-related mutations
      (A1101T and P1879S) at the sodium channel and expression levels of the cytochrome
      P450 gene CYP6BG1 were examined individually using laboratory and field strains
      of P. xylostella. Real-time quantitative PCR analysis using the laboratory
      strains revealed that levels of larval expression of the resistant strain,
      homozygous for the pyrethroid-resistant alleles other than the M918I, are
      significantly higher than those of the susceptible strain. In the field strains,
      the expression levels in insects having the same resistant alleles as those of
      the resistant strains varied greatly among individuals. The expression levels
      were not significantly higher than those in the heterozygotes. CONCLUSION:
      Significant correlation between the target insensitivity and the increased
      metabolic detoxification in pyrethroid resistance of P. xylostella was observed
      in the laboratory but not in the field.

PMID- 20146260
TI  - Induction of avian musculoaponeurotic fibrosarcoma proteins by toxic bile acid
      inhibits expression of glutathione synthetic enzymes and contributes to
      cholestatic liver injury in mice.
AB  - We previously showed that hepatic expression of glutathione (GSH) synthetic
      enzymes and GSH levels fell 2 weeks after bile duct ligation (BDL) in mice. This
      correlated with a switch in nuclear anti-oxidant response element (ARE) binding
      activity from nuclear factor erythroid 2-related factor 2 (Nrf2) to c-avian
      musculoaponeurotic fibrosarcoma (c-Maf)/V-maf musculoaponeurotic fibrosarcoma
      oncogene homolog G (MafG). Our current aims were to examine whether the switch in
      ARE binding activity from Nrf2 to Mafs is responsible for decreased expression of
      GSH synthetic enzymes and the outcome of blocking this switch. Huh7 cells treated
      with lithocholic acid (LCA) exhibited a similar pattern of change in GSH
      synthetic enzyme expression as BDL mice. Nuclear protein levels of Nrf2 fell at
      20 hours after LCA treatment, whereas c-Maf and MafG remained persistently
      induced. These changes translated to ARE nuclear binding activity. Knockdown of c
      Maf or MafG individually blunted the LCA-induced decrease in Nrf2 ARE binding and
      increased ARE-dependent promoter activity, whereas combined knockdown was more
      effective. Knockdown of c-Maf or MafG individually increased the expression of
      GSH synthetic enzymes and raised GSH levels, and combined knockdown exerted an
      additive effect. Ursodeoxycholic acid (UDCA) or S-adenosylmethionine (SAMe)
      prevented the LCA-induced decrease in expression of GSH synthetic enzymes and
      promoter activity and prevented the increase in MafG and c-Maf levels. In vivo
      knockdown of the Maf genes protected against the decrease in GSH enzyme
      expression, GSH level, and liver injury after BDL. CONCLUSION: Toxic bile acid
      induces a switch from Nrf2 to c-Maf/MafG ARE nuclear binding, which leads to
      decreased expression of GSH synthetic enzymes and GSH levels and contributes to
      liver injury during BDL. UDCA and SAMe treatment targets this switch.

PMID- 20146262
TI  - On form dictating function: shape and structural effects in silica-based
      functional materials.
AB  - Along with basic physicochemical properties, the morphology of sol-gel materials,
      both on the macro-, meso-, and nanoscale, controls function and utility.
      Referring to recent achievements, we focus on the relation between form and
      activity for functional silica-based materials to elucidate a few general
      concepts of usefulness in guiding research in this burgeoning field.

PMID- 20146261
TI  - Deletion of CD39 on natural killer cells attenuates hepatic ischemia/reperfusion
      injury in mice.
AB  - Natural killer (NK) cells play crucial roles in innate immunity and express CD39
      (Ecto-nucleoside triphosphate diphosphohydrolase 1 [E-NTPD1]), a rate-limiting
      ectonucleotidase in the phosphohydrolysis of extracellular nucleotides to
      adenosine. We have studied the effects of CD39 gene deletion on NK cells in
      dictating outcomes after partial hepatic ischemia/reperfusion injury (IRI). We
      show in mice that gene deletion of CD39 is associated with marked decreases in
      phosphohydrolysis of adenosine triphosphate (ATP) and adenosine diphosphate to
      adenosine monophosphate on NK cells, thereby modulating the type-2 purinergic
      (P2) receptors demonstrated on these cells. We note that CD39-null mice are
      protected from acute vascular injury after single-lobe warm IRI, and, relative to
      control wild-type mice, display significantly less elevation of aminotransferases
      with less pronounced histopathological changes associated with IRI. Selective
      adoptive transfers of immune cells into Rag2/common gamma null mice (deficient in
      T cells, B cells, and NK/NKT cells) suggest that it is CD39 deletion on NK cells
      that provides end-organ protection, which is comparable to that seen in the
      absence of interferon gamma. Indeed, NK effector mechanisms such as interferon
      gamma secretion are inhibited by P2 receptor activation in vitro. Specifically,
      ATPgammaS (a nonhydrolyzable ATP analog) inhibits secretion of interferon gamma
      by NK cells in response to interleukin-12 and interleukin-18, providing a
      mechanistic link between CD39 deletion and altered cytokine secretion.
      CONCLUSION: We propose that CD39 deficiency and changes in P2 receptor activation
      abrogate secretion of interferon gamma by NK cells in response to inflammatory
      mediators, thereby limiting tissue damage mediated by these innate immune cells
      during IRI.

PMID- 20146263
TI  - Caveolin-1 is enriched in the peroxisomal membrane of rat hepatocytes.
AB  - Caveolae are a subtype of cholesterol-enriched lipid microdomains/rafts that are
      routinely detected as vesicles pinching off from the plasma membrane. Caveolin-1
      is an essential component of caveolae. Hepatic caveolin-1 plays an important role
      in liver regeneration and lipid metabolism. Expression of caveolin-1 in
      hepatocytes is relatively low, and it has been suggested to also reside at other
      subcellular locations than the plasma membrane. Recently, we found that the
      peroxisomal membrane contains lipid microdomains. Like caveolin-1, hepatic
      peroxisomes are involved in lipid metabolism. Here, we analyzed the subcellular
      location of caveolin-1 in rat hepatocytes. The subcellular location of rat
      hepatocyte caveolin-1 was analyzed by cell fractionation procedures,
      immunofluorescence, and immuno-electron microscopy. Green fluorescent protein
      (GFP)-tagged caveolin-1 was expressed in rat hepatocytes. Lipid rafts were
      characterized after Triton X-100 or Lubrol WX extraction of purified peroxisomes.
      Fenofibric acid-dependent regulation of caveolin-1 was analyzed. Peroxisome
      biogenesis was studied in rat hepatocytes after RNA interference-mediated
      silencing of caveolin-1 and caveolin-1 knockout mice. Cell fractionation and
      microscopic analyses reveal that caveolin-1 colocalizes with peroxisomal marker
      proteins (catalase, the 70 kDa peroxisomal membrane protein PMP70, the
      adrenoleukodystrophy protein ALDP, Pex14p, and the bile acid-coenzyme A:amino
      acid N-acyltransferase BAAT) in rat hepatocytes. Artificially expressed GFP
      caveolin-1 accumulated in catalase-positive organelles. Peroxisomal caveolin-1 is
      associated with detergent-resistant microdomains. Caveolin-1 expression is
      strongly repressed by the peroxisome proliferator-activated receptor-alpha
      agonist fenofibric acid. Targeting of peroxisomal matrix proteins and peroxisome
      number and shape were not altered in rat hepatocytes with 70%-80% reduced
      caveolin-1 levels and in livers of caveolin-1 knockout mice. CONCLUSION: Caveolin
      1 is enriched in peroxisomes of hepatocytes. Caveolin-1 is not required for
      peroxisome biogenesis, but this unique subcellular location may determine its
      important role in hepatocyte proliferation and lipid metabolism.

PMID- 20146264
TI  - MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor
      gene expression by interleukin-6 in human malignant cholangiocytes.
AB  - Although the inflammation-associated cytokine interleukin-6 (IL-6) has been
      implicated in cholangiocarcinoma growth, the relationship between IL-6 and
      oncogenic changes is unknown. IL-6 can increase expression of DNA
      methyltransferase-1 (DNMT-1) and epigenetically regulate the expression of
      several genes, including microRNAs (miRNAs). DNMT-1 up-regulation occurs in
      hepatobiliary cancers and is associated with a poor prognosis. To understand the
      potential regulation of DNMT-1 by IL-6-dependent miRNAs, we examined the
      expression of a group of miRNAs which have sequence complementarity to the 3'
      untranslated region of DNMT-1, namely miR-148a, miR-152, and miR-301. The
      expression of these miRNAs was decreased in cholangiocarcinoma cells. Moreover,
      the expression of all three miRNAs was decreased in IL-6-overexpressing malignant
      cholangiocytes in vitro and in tumor cell xenografts. There was a concomitant
      decrease in expression of the methylation-sensitive tumor suppressor genes
      Rassf1a and p16INK4a. Using luciferase reporter constructs, DNMT-1 was verified
      as a target for miR-148a and miR-152. Precursors to miR-148a and miR-152
      decreased DNMT-1 protein expression, increased Rassf1a and p16INK4a expression,
      and reduced cell proliferation. CONCLUSION: These data indicate that IL-6 can
      regulate the activity of DNMT-1 and expression of methylation-dependent tumor
      suppressor genes by modulation of miR-148a and miR-152, and provide a link
      between this inflammation-associated cytokine and oncogenesis in
      cholangiocarcinoma.

PMID- 20146265
TI  - Heat-solubilized curry spice curcumin inhibits antibody-antigen interaction in in
      vitro studies: a possible therapy to alleviate autoimmune disorders.
AB  - Chronic and complex autoimmune diseases, currently treated palliatively with
      immunosuppressives, require multi-targeted therapy for greater effectiveness. The
      naturally occurring polyphenol curcumin has emerged as a powerful "nutraceutical"
      that interacts with multiple targets to regress diseases safely and
      inexpensively. Up to 8 g/day of curcumin for 18 months was non-toxic to humans.
      However, curcumin's utility is limited by its aqueous insolubility. We have
      demonstrated a heat-mediated 12-fold increase in curcumin's aqueous solubility.
      Here, we show by SDS-PAGE and surface plasmon resonance that heat-solubilized
      curcumin binds to proteins. Based on this binding we hypothesized that heat
      solubilized curcumin or turmeric would prevent autoantibody targeting of cognate
      autoantigens. Heat-solubilized curcumin/turmeric significantly decreased binding
      of autoantibodies from Sjogren's syndrome (up to 43/70%, respectively) and
      systemic lupus erythematosus (up to 52/70%, respectively) patients as well as an
      animal model of Sjogren's syndrome (up to 50/60%, respectively) to their cognate
      antigens. However, inhibition was not specific to autoimmunity. Heat-solubilized
      curcumin/turmeric also inhibited binding of commercial polyclonal anti-spectrin
      to spectrin (50/56%, respectively). Thus, we suggest that the multifaceted heat
      solubilized curcumin can ameliorate autoimmune disorders. In addition, the non
      toxic curcumin could serve as a new protein stain in SDS-PAGE even though it is
      less sensitive than the Coomassie system which involves toxic chemicals.

PMID- 20146266
TI  - Transforming growth factor-beta and notch signaling mediate stem cell
      differentiation into smooth muscle cells.
AB  - The differentiation of stem cells into smooth muscle cells (SMCs) plays an
      important role in vascular development and remodeling. In addition, stem cells
      represent a potential source of SMCs for regenerative medicine applications such
      as constructing vascular grafts. Previous studies have suggested that various
      biochemical factors, including transforming growth factor-beta (TGF-beta) and the
      Notch pathway, may play important roles in vascular differentiation. However, the
      interactions of these two signaling pathways in the differentiation of bone
      marrow mesenchymal stem cells (MSCs) have not been clearly defined. In this
      study, we profiled the gene expression in MSCs in response to TGF-beta, and
      showed that TGF-beta induced Notch ligand Jagged 1 (JAG1) and SMC markers,
      including smooth muscle alpha-actin (ACTA2), calponin 1 (CNN1), and myocardin
      (MYOCD), which were dependent on the activation of SMAD3 and Rho kinase. In
      addition, knocking down JAG1 expression partially blocked ACTA2 and CNN1
      expression and completely blocked MYOCD expression, suggesting that JAG1 plays an
      important role in TGF-beta-induced expression of SMC markers. On the other hand,
      the activation of Notch signaling induced the expression of SMC markers in MSCs
      and human embryonic stem cells (hESCs). Notch activation in hESCs also resulted
      in an increase of neural markers and a decrease of endothelial markers. These
      results suggest that Notch signaling mediates TGF-beta regulation of MSC
      differentiation and that Notch signaling induces the differentiation of MSCs and
      hESCs into SMCs, which represents a novel mechanism involved in stem cell
      differentiation.

PMID- 20146267
TI  - A novel mechanism underlying phytate-mediated biological action-phytate
      hydrolysates induce intracellular calcium signaling by a Galphaq protein-coupled
      receptor and phospholipase C-dependent mechanism in colorectal cancer cells.
AB  - Phytate (inositol hexa-phosphate, IP6) possesses multiple biological functions
      including anticancer activity. IP6 is converted to inositol di-, tri-, and tetra
      phosphates (IP2, IP3, and IP4) by phytase in large intestinal microbes; however,
      their contribution to the IP6-mediated functions has not been investigated. We
      have developed the preparations of IP2-4 and IP3-rich phytate hydrolysate (IP3
      RPH) by IP6 digestion using microbial phytase, and examined the induction of
      intracellular Ca(2+) signaling in response to the preparations in colorectal
      cancer cells. IP2-4, but not inositol (IP0) and IP6, induced increases in
      intracellular Ca(2+) concentration ([Ca(2+)](i)) in Caco-2 cells with the
      following rank order: IP3>IP2=IP4. Inositol tri-phosphate (IP3)-RPH induced
      increases in [Ca(2+)](i) in both undifferentiated Caco-2 and HT-29 cells, but not
      in differentiated Caco-2. The IP3-RPH-induced [Ca(2+)](i) increase was resistant
      to extracellular Ca(2+) depletion, however, it was impaired by inhibitors of
      phospholipase C, inositol 1, 4, 5 tri-phosphate receptor, ryanodine receptor, and
      Galphaq protein. These results show that the putative G protein-coupled receptor
      on the plasma membrane senses the IP6 hydrolysates and activates phospholipase
      Cbeta, resulting in Ca(2+) mobilization through Ca(2+) channels coupled with the
      inositol 1, 4, 5 tri-phosphate and ryanodine receptors on the sarco-endoplasmic
      reticulum Ca(2+) store in colorectal cancer cells.

PMID- 20146268
TI  - Efficient intramolecular hydroalkoxylation of unactivated alkenols mediated by
      recyclable lanthanide triflate ionic liquids: scope and mechanism.
AB  - Lanthanide triflate complexes of the type [Ln(OTf)(3)] (Ln=La, Sm, Nd, Yb, Lu)
      serve as effective, recyclable catalysts for the rapid intramolecular
      hydroalkoxylation (HO)/cyclization of primary/secondary and aliphatic/aromatic
      hydroxyalkenes in imidazolium-based room-temperature ionic liquids (RTILs) to
      yield the corresponding furan, pyran, spirobicyclic furan, spirobicyclic
      furan/pyran, benzofuran, and isochroman derivatives. Products are
      straightforwardly isolated from the catalytic solution, conversions exhibit
      Markovnikov regioselectivity, and turnover frequencies are as high as 47 h(-1) at
      120 degrees C. The ring-size rate dependence of the primary alkenol cyclizations
      is 5>6, consistent with a sterically controlled transition state. The
      hydroalkoxylation/cyclization rates of terminal alkenols are slightly more rapid
      than those of internal alkenols, which suggests modest steric demands in the
      cyclic transition state. Cyclization rates of aryl-functionalized hydroxyalkenes
      are more rapid than those of the linear alkenols, whereas five- and five/six
      membered spirobicyclic skeletons are also regioselectively closed. In cyclization
      of primary, sterically encumbered alkenols, turnover-frequency dependence on
      metal-ionic radius decreases by approximately 80-fold on going from La(3+) (1.160
      A) to Lu(3+) (0.977 A), presumably reflecting steric impediments along the
      reaction coordinate. The overall rate law for alkenol
      hydroalkoxylation/cyclization is v approximately k[catalyst](1)[alkenol](1). An
      observed ROH/ROD kinetic isotope effect of 2.48 (9) is suggestive of a catalytic
      pathway that involves kinetically significant intramolecular proton transfer. The
      present activation parameters--enthalpy (DeltaH(++))=18.2 (9) kcal mol(-1),
      entropy (DeltaS(++))=-17.0 (1.4) eu, and energy (E(a))=18.2 (8) kcal mol(-1)-
      suggest a highly organized transition state. Proton scavenging and coordinative
      probing results suggest that the lanthanide triflates are not simply precursors
      of free triflic acid. Based on the kinetic and mechanistic evidence, the proposed
      catalytic pathway invokes hydroxyl and olefin activation by the electron
      deficient Ln(3+) center, and intramolecular H(+) transfer, followed by alkoxide
      nucleophilic attack with ring closure.

PMID- 20146269
TI  - Synthesis of monomeric and dimeric repeating units of the zwitterionic type 1
      capsular polysaccharide from Streptococcus pneumoniae.
AB  - Zwitterionic polysaccharides (ZPSs) from Bacteroides fragilis and Streptococcus
      pneumoniae display unique T-cell activities. The first synthesis of a
      hexasaccharide representing two repeating units of the zwitterionic capsular
      polysaccharide from S. pneumoniae type 1 (Sp1) is reported. Key elements of the
      approach are stereoselective construction of 1,4-cis-alpha-galactose linkages
      based on a reactive trichloroacetimidate donor that incorporates a 6-O-acetyl
      group, which may contribute to the high alpha selectivity in glycosylation. After
      assembly of the fully protected hexasaccharide from five monosaccharide synthons
      2-4, 24 and 25, selective deprotection of the primary hydroxyl groups of the four
      galactose residues followed by oxidation to the corresponding uronic acids
      provides hexasaccharide 19. The trisaccharide counterpart 1 was synthesized in
      similar fashion from three synthons, 2-4. This approach employed both
      conventional and dehydrative glycosylation methodologies and avoids the use of
      poorly reactive uronic acid derived glycosyl donors and acceptors.

PMID- 20146270
TI  - Speciation of aluminium in mixtures of the ionic liquids [C3mpip][NTf2] and
      [C4mpyr][NTf2] with AlCl3: an electrochemical and NMR spectroscopy study.
AB  - This paper reports on the electrodeposition of aluminium on several substrates
      from the air- and water-stable ionic liquids 1-propyl-1-methylpiperidinium
      bis(trifluoromethylsulfonyl)amide ([C(3)mpip][NTf(2)]) and 1-butyl-1
      methylpyrrolidinium bis(trifluoromethylsulfonyl)amide ([C(4)mpyr][NTf(2)]), which
      contain anhydrous AlCl(3). At an AlCl(3) concentration of 0.75 molal, no evidence
      for aluminium electrodeposition was observed in either system at room
      temperature. However, aluminium electrodeposition becomes feasible upon heating
      the samples to 80 degrees C. Aluminium electrodeposition from
      bis(trifluoromethylsulfonyl)amide-based ionic liquids that contain AlCl(3) has
      previously been shown to be very dependent upon the AlCl(3) concentration and has
      not been demonstrated at AlCl(3) concentrations below 1.13 molal. The dissolution
      of AlCl(3) in [C(3)mpip][NTf(2)] and [C(4)mpyr][NTf(2)] was studied by variable
      temperature (27)Al NMR spectroscopy to gain insights on the electroactive species
      responsible for aluminium electrodeposition. A similar change in the aluminium
      speciation with temperature was observed in both ionic liquids, thereby
      indicating that the chemistry was similar in both. The electrodeposition of
      aluminium was shown to coincide with the formation of an asymmetric four
      coordinate aluminium-containing species with an (27)Al chemical shift of delta=94
      and 92 ppm in the [C(3)mpip][NTf(2)]-AlCl(3) and [C(4)mpyr][NTf(2)]-AlCl(3)
      systems, respectively. It was concluded that the aluminium-containing species
      that give rise to these resonances corresponds to the electroactive species and
      was assigned to [AlCl(3)(NTf(2))](-).

PMID- 20146271
TI  - Electronic structure and reactivity of a [1],[1]disilamolybdenocenophane.
AB  - The electronic structure of the two-fold bridged [1],[1]disilamolybdenocenophane
      has been analyzed by means of density functional theory. As predicted, the
      relatively high charge at the metal center and, in particular, the highly
      strained geometry determine a noticeable reactivity towards unsaturated organic
      substrates. Thus, treatment with the nonpolar reagents 2-butyne and azobenzene
      leads to side-on coordination of the substrate to the metal center, whereas the
      reaction with polar tert-butylisonitrile gives a highly unusual structural motif
      in the form of an ansa-carbene.

PMID- 20146272
TI  - Trihydroxytrioxatriangulene--an extended fluorescein and a ratiometric pH sensor.

PMID- 20146273
TI  - Metal dependence of network dimensionality in 1,2,4-diazaphospholide coordination
      polymers.

PMID- 20146274
TI  - Elucidation of metal-ion accumulation induced by hydrogen bonds on protein
      surfaces by using porous lysozyme crystals containing Rh(III) ions as the model
      surfaces.
AB  - Metal-ion accumulation on protein surfaces is a crucial step in the initiation of
      small-metal clusters and the formation of inorganic materials in nature. This
      event is expected to control the nucleation, growth, and position of the
      materials. There remain many unknowns, as to how proteins affect the initial
      process at the atomic level, although multistep assembly processes of the
      materials formation by both native and model systems have been clarified at the
      macroscopic level. Herein the cooperative effects of amino acids and hydrogen
      bonds promoting metal accumulation reactions are clarified by using porous hen
      egg white lysozyme (HEWL) crystals containing Rh(III) ions, as model protein
      surfaces for the reactions. The experimental results reveal noteworthy
      implications for initiation of metal accumulation, which involve highly
      cooperative dynamics of amino acids and hydrogen bonds: i) Disruption of hydrogen
      bonds can induce conformational changes of amino-acid residues to capture Rh(III)
      ions. ii) Water molecules pre-organized by hydrogen bonds can stabilize Rh(III)
      coordination as aqua ligands. iii) Water molecules participating in hydrogen
      bonds with amino-acid residues can be replaced by Rh(III) ions to form
      polynuclear structures with the residues. iv) Rh(III) aqua complexes are retained
      on amino-acid residues through stabilizing hydrogen bonds even at low pH
      (approximately 2). These metal-protein interactions including hydrogen bonds may
      promote native metal accumulation reactions and also may be useful in the
      preparation of new inorganic materials that incorporate proteins.

PMID- 20146275
TI  - Rhodium(I)-catalyzed enantioselective activation of cyclobutanols: formation of
      cyclohexane derivatives with quaternary stereogenic centers.
AB  - The activation of carbon-carbon sigma bonds is a complementary method to access
      uncommon and difficult-to-prepare organometallic species. Herein, we describe the
      activation of tert-cyclobutanols through an enantioselective insertion of a
      chiral rhodium(I) complex into the C-C sigma bond of the cyclobutane, forming a
      quaternary stereogenic center and an alkyl-rhodium functionality that initiates
      ring-closure reactions. This technology provides access to a variety of
      substituted cyclohexane derivatives with quaternary stereogenic centers. The
      formation of different product families can be controlled by the employed set of
      reaction conditions and additives. In general, high yields and excellent
      enantioselectivities of up to 99% ee are obtained.

PMID- 20146276
TI  - Biological iron-monosulfide production for efficient electricity harvesting from
      a deep-sea metal-reducing bacterium.

PMID- 20146277
TI  - Classification of a novel surface phase transition: the knight-move phase.
AB  - The knight move or (square root(5) x square root(5)) R27 degree phase occurs on
      some surfaces relevant for growth of high-T(c) superconducting films and other
      technologically significant surfaces. The nature of the disordering transition of
      this phase has not been determined. We demonstrate via simulation that this
      disordering transition is first-order (discontinuous), a result with important
      implications for preparation of the surfaces in question.

PMID- 20146279
TI  - Surface-aligned femtochemistry: real-time dynamics of photoinduced I2 formation
      from CD3I on MgO(100).

PMID- 20146278
TI  - A complex of 2-hydroxyisocaproyl-coenzyme A dehydratase and its activator from
      Clostridium difficile stabilized by aluminium tetrafluoride-adenosine
      diphosphate.
AB  - The dehydration of 2-hydroxyisocaproyl-CoA to isocaprenoyl-CoA is the chemically
      most demanding step in the reduction of leucine to isocaproate by Clostridium
      difficile, because the beta-hydrogen of the substrate is not acidic (pK(a) ca.
      40). A two-component system, composed of a homodimeric activator and an
      heterodimeric dehydratase, catalyses this unusual alpha,beta-elimination of
      water. The reduced activator transfers an electron from its [4Fe-4S](+) cluster
      to that of the dehydratase in an ATP-dependent manner, similar to the iron
      protein of nitrogenase. Here we show that AlF(4)(-) x ADP traps the interaction
      of the activator with the dehydratase by forming a stable complex containing 1.0
      mol homodimeric activator, 1.0 mol heterodimeric dehydratase and 1.2 mol ADP. The
      complex (148 kDa) was isolated by size exclusion chromatography, affinity
      chromatography using the Strep-tag at the activator, or most conveniently by
      ultrafiltration (100 kDa cut off membrane). Kinetic and EPR-spectroscopic
      experiments revealed that the complex formation proceeds much slower than the
      activation but in an almost irreversible manner. The isolated complex is devoid
      of any activity, because the dehydratase is in the oxidized form whereas the
      activator remains in the reduced state due to the presence of dithionite.

PMID- 20146280
TI  - Fluorescence quenching by oxygen: "debunking" a classic rule.

PMID- 20146281
TI  - Generation of highly damaging H2O+ radicals by inner valence shell ionization of
      water.

PMID- 20146282
TI  - The hERG potassium channel and drug trapping: insight from docking studies with
      propafenone derivatives.
AB  - The inner cavity of the hERG potassium ion channel can accommodate large,
      structurally diverse compounds that can be trapped in the channel by closure of
      the activation gate. A small set of propafenone derivatives was synthesized, and
      both use-dependency and recovery from block were tested in order to gain insight
      into the behavior of these compounds with respect to trapping and non-trapping.
      Ligand-protein docking into homology models of the closed and open state of the
      hERG channel provides the first evidence for the molecular basis of drug
      trapping.

PMID- 20146283
TI  - Enantiospecific stereodivergent synthesis of trans- and cis-N(2),3-dimethyl-4
      phenyl-1,2,3,4-tetrahydroisoquinolines.
AB  - The acid-promoted cyclizations of a range of N-benzylethanolamines (derived from
      pseudoephedrine or ephedrine) give the corresponding trans-N(2),3-dimethyl-4
      phenyl-1,2,3,4-tetrahydroisoquinolines with high levels of diastereoselectivity
      and in good yields of isolated product. The cyclizations of the corresponding
      chromium tricarbonyl complexes are rendered completely stereoselective. Acid
      promoted cyclization of N-(3',4'-dimethoxybenzyl)ephedrine and its chromium
      tricarbonyl complex occur with complementary diastereoselectivities to give trans
      and cis-N(2),3-dimethyl-4-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline,
      respectively, in >99:1 d.r. The latter is consistent with a "double inversion"
      mechanism, which involves neighboring group participation by the chromium
      tricarbonyl moiety followed by rearomatization to give the corresponding cis
      tetrahydroisoquinoline with overall retention of configuration.

PMID- 20146284
TI  - Electrografted poly(N-mercaptoethyl acrylamide) and Au nanoparticles-based
      organic/inorganic film: a platform for the high-performance electrochemical
      biosensors.
AB  - In this study, we describe the use of the combination of eletrografting poly(N
      mercaptoethyl acrylamide) and Au nanoparticles in the construction of high
      performance biosensors. The poly(N-mercaptoethyl acrylamide) was electrografted
      onto the glassy carbon electrode surface, which provided a strongly adhering
      primer film for the stable attachment of Au nanoparticles and horseradish
      peroxidase (HRP) enzymes. The performances of the biosensors based on the HRP
      immobilized in the Au/poly(N-mercaptoethyl acrylamide) composite film were
      investigated. A couple of redox peaks were obtained, indicating that the Au
      nanoparticles could facilitate the direct-electron transfer between HRP and the
      underlying electrode. The biosensor showed an excellent electrocatalytic activity
      toward the reduction of hydrogen oxide and long-term stability, owing to the
      stable electrografted film and biocompatible Au nanoparticles. Our results
      demonstrate that the combination of electrografting and Au nanoparticles provides
      a promising platform for the immobilization of biomolecules and analysis of redox
      enzymes for their sensing applications.

PMID- 20146285
TI  - Superior anion-binding properties of a cryptand-like oligopyrrolic macrocycle.

PMID- 20146286
TI  - Methylguanidinium borohydride: an ionic-liquid-based hydrogen-storage material.

PMID- 20146287
TI  - Aqueous CTAB-assisted electrodeposition of gold atomic clusters and their oxygen
      reduction electrocatalytic activity in acid solutions.
AB  - Gradual, yet a great leap: electrosynthesized surfactant-stabilized gold atomic
      clusters (AuACs; Au(n) , 5<=n<=13) electrocatalyze the oxygen reduction reaction
      (ORR) in acid solution at low overpotentials. Depending on the surfactant
      concentration, the ORR mechanism gradually transits from a direct four-electron
      to a two-electron pathway (see picture; SHE=standard hydrogen electrode), which
      suggests the transformation of atomic clusters into nanoparticles.

PMID- 20146288
TI  - Philic and phobic segregation in liquid-crystal ionic dendrimers: an enthalpy
      entropy competition.

PMID- 20146289
TI  - General and chemoselective N-transacylation of secondary amides by means of
      perfluorinated anhydrides.

PMID- 20146290
TI  - Acylated serine derivatives: a unique class of arthropod pheromones of the
      Australian redback spider, Latrodectus hasselti.

PMID- 20146291
TI  - Total synthesis of the antibiotic branimycin.

PMID- 20146294
TI  - Multistep phase-switch synthesis by using liquid-liquid partitioning of boronic
      acids: productive tags with an expanded repertoire of compatible reactions.
AB  - Tagging along: a system for phase-switch synthesis has been developed. The
      boronic acid functionality is used as a phase tag that complexes to sorbitol and
      facilitates compound transfer from an organic solvent to water at high pH. The
      phase tag can then be used in a productive reaction step to generate targeted
      products, thereby eliminating purification by silica gel chromatography.

PMID- 20146293
TI  - Enantioselective biocatalytic oxidative desymmetrization of substituted
      pyrrolidines.

PMID- 20146292
TI  - A simple spectroscopic method for differentiating cellular uptakes of gold
      nanospheres and nanorods from their mixtures.

PMID- 20146295
TI  - ipso-Nitration of arenes.

PMID- 20146296
TI  - Synthesis of nine-membered carbocycles by the [4+3+2] cycloaddition reaction of
      ethyl cyclopropylideneacetate and dienynes.

PMID- 20146297
TI  - "Hot" surface activation of molecular complexes: insight from modeling studies.

PMID- 20146300
TI  - Role of the SNK-SPAR pathway in the development of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by the presence of senile plaques and
      neurofibrillary tangles in the brain. The beta-amyloid peptide (Abeta) is the
      primary constituent of the senile plaques, and has been proposed to be a key
      contributor to the neurodegeneration observed in AD. The molecular mechanisms
      underlying dendritic spine damage that is induced by Abeta toxicity in AD
      patients remain largely unknown. It has been suggested previously that the SNK
      SPAR signaling pathway is involved in activity-dependent remodeling of synapses.
      The relationship between the SNK-SPAR pathway and Abeta-induced excitotoxicity,
      however, is poorly understood. The present study investigated the effects of
      bilateral intrahippocampal injection of Abeta peptide 1-40 (Abeta(1-40)) on
      learning and memory in the rat, and explored the mechanisms underlying the
      effects of this injection. We reported that bilateral injection of Abeta(1-40) in
      rats resulted in impaired performance in the step-down passive avoidance and
      Morris water maze tasks. Then we examined mRNA and protein expression levels in
      the different brain regions one week after injection with Abeta(1-40) and found
      that the SNK-SPAR signaling pathway was possibly involved in dendritic spine
      damage in the different brain regions of Abeta-treated rats. These results
      demonstrate that the SNK-SPAR pathway may possibly play a crucial role in Abeta
      induced excitotoxic damage in the central nervous system by regulating synaptic
      stability.

PMID- 20146301
TI  - Is iPS cell the panacea?
AB  - In 2006, it was reported that transgenic expression of merely four defined
      transcription factors (c-Myc, Klf4, Oct4, and Sox2) is sufficient to reprogram
      somatic cells to a pluripotent state. The resulting induced pluripotent stem
      (iPS) cells ignited intense interest in the field of life science for their
      promising applications in basic biology, drug development, and transplantation.
      However, the underlying problems of iPS cells seem to be ignored. This review
      shed light on the problems pertaining iPS cells, including the elusive origin,
      risk of tumorgenesis, and its relationship with natural selection.

PMID- 20146302
TI  - Podoplanin is a useful marker for identifying mesothelioma in malignant
      effusions.
AB  - The diagnosis of malignant mesothelioma in serosal effusions continues to be a
      major challenge because some of its cytomorphological features closely resemble
      adenocarcinomas. Immunohistochemistry is a valuable tool in the differentiation
      of epithelioid mesothelioma from metastatic adenocarcinomas. However, no single
      antibody has demonstrated absolute sensitivity or specificity. In this study, we
      evaluated the value of immunostaining pattern for podoplanin to differentiate
      mesothelioma from adenocarcinomas of various origins.Cell blocks from previously
      collected paraffin-embedded cell blocks of 86 effusions (18 mesothelioma, 35
      reactive mesothelium, 9 breast adenocarcinoma, 14 ovarian adenocarcinoma, and 10
      lung adenocarcinoma) were retrieved from the file of the Department of Pathology
      at University of Michigan and Lund University in Sweden and were used for the
      study. Slides prepared from the cell blocks were stained for podoplanin. The
      percentage of immunostained cells was recorded as follows: 1+ (5-25%), 2+ (26
      50%), and 3+ (>50%). A stain result involving <5% of cells was considered
      negative. The intensity of positive results was evaluated as strong, moderate, or
      weak.Podoplanin is expressed in 94% of malignant mesothelioma cases (17/18), 97%
      (30/31) of cases of reactive mesothelial, 0% of lung adenocarcinoma cases (0/9),
      0% of breast adenocarcinoma (0/9), and 7% of ovarian adenocarcinoma (1/14). All
      positive cases of malignant mesothelioma and reactive mesothelium showed strong
      membranous reactivity to podoplanin. The one positive case of ovarian
      adenocarcinoma showed a weak membranous podoplanin immunostaining.On the basis of
      our results and published data, we believe that membranous podoplanin
      immunoreactivity, in conjunction with calretinin, would be more specific than
      CK5/6 and WT-1 in differentiating epithelioid malignant mesothelioma from
      adenocarcinoma of the lung, breast, and ovary.

PMID- 20146303
TI  - Morphologic features of prostatic adenocarcinoma on ThinPrep(r) urinary cytology.
AB  - Malignant cells of prostatic adenocarcinoma are rarely identified in urine. In
      most cases, this finding is associated with high stage tumor. Numerous
      descriptions of the morphology of prostatic adenocarcinoma have been reported
      using cytocentrifugated specimens. However, no specific morphologic description
      of prostatic adenocarcinoma in urine using liquid-based cytology has been
      previously described. Four cases of prostatic adenocarcinoma in urine using
      ThinPrep(r) liquid-based preparations were identified between 2002 and 2009 at
      the University of Wisconsin Hospital and Clinics. Three patients had either high
      stage tumor or metastatic disease at the time of diagnosis, while the remaining
      patient had low stage tumor. The morphology of each case was evaluated with
      specific attention to cell size, nuclear characteristics, nuclear to cytoplasmic
      ratio, and cytoplasmic characteristics. The resulting key features for prostatic
      adenocarcinoma in urine are clustering, increased nuclear to cytoplasmic ratio,
      and prominent nucleoli. Though typically the presence of prostatic adenocarcinoma
      in urine implies high stage tumor, cells of lower stage tumors may be seen in
      urine as well.

PMID- 20146304
TI  - Immunohistochemistry on squash smears: A diagnostic aid.

PMID- 20146306
TI  - Arterial access and door-to-balloon times for primary percutaneous coronary
      intervention in patients presenting with acute ST-elevation myocardial
      infarction.
AB  - OBJECTIVES: This study compares the transradial versus the transfemoral approach
      for time to intervention for patients presenting with ST elevation myocardial
      infarction (STEMI). BACKGROUND: Survival following STEMI is associated with
      reperfusion times (door-to-balloon; D2B). For patients undergoing primary PCI for
      acute STEMI, potential effects of transradial approach (r-PCI) as compared with
      the femoral artery approach (f-PCI) on D2B times have not been extensively
      studied. METHODS: Consecutive patients presenting with STEMI at a tertiary care
      medical center were enrolled in a comprehensive-Heart Alert program (HA) and
      included in this analysis. Time parameters measured included: door-to-ECG, ECG-to
      HA activation, HA activation-to-cath lab team arrival, patient arrival in cath
      lab to arterial access, and arterial access-to-balloon inflation. RESULTS: Of 240
      total patients, 205 underwent successful PCI (n = 124 r-PCI; n = 116 f-PCI). No
      significant difference was observed in the pre-cath lab times. Mean case start
      times for r-PCI took significantly longer (12.5 +/- 5.4 min vs. 10.5 +/- 5.7 min,
      P = 0.005) due to patient preparation. Once arterial access was obtained, balloon
      inflation occurred faster in the r-PCI group (18.3 vs. 24.1 min; P < 0.001).
      Total time from patient arrival to the cardiac cath lab to PCI was reduced in the
      r-PCI as compared to the f-PCI group (28.4 vs. 32.7 min, P = 0.01). There was a
      small but statistical difference in D2B time (r-PCI 76.4 min vs. f-PCI 86.5 min P
      = 0.008). CONCLUSIONS: Patients presenting with STEMI can undergo successful PCI
      via radial artery approach without compromise in D2B times as compared to femoral
      artery approach.

PMID- 20146307
TI  - "Buddy in jail" or "buried wire" method: a critical review.

PMID- 20146308
TI  - In reference to Electromyographic facial nerve monitoring during parotidectomy
      for benign lesions does not improve the outcome of postoperative facial nerve
      function: a prospective two-center trial.

PMID- 20146310
TI  - Pulmonary artery stents: long-term follow-up.
AB  - OBJECTIVES: Determine the long-term outcomes of branch pulmonary artery (PA)
      stents. BACKGROUND: PA stents in congenital heart disease effectively relieve
      stenoses in the short-term. Published long-term data are limited. METHODS:
      Patients enrolled in an FDA IDE protocol from 1989-92 were included. Clinical
      follow-up and catheterization data were evaluated. Patients were included if >5
      year follow-up data was available or if mortality occurred following the initial
      procedure. RESULTS: There were five deaths: four due to progression of their
      underlying heart disease, and one from a complication during a follow-up
      catheterization. Clinical data for 43 surviving patients demonstrated 39 patients
      (91%) are in NYHA class I or II. Seven patients underwent surgical intervention
      during the follow-up period (five RV-PA conduit, two Fontan revisions), but none
      addressed PA stenosis. Final repeat catheterizations were performed in 36
      patients (55 stents) 7.2 +/- 4.3 years post stent insertion with 1.2 +/- 0.9
      further procedures with stent dilations. In this subgroup, the minimum vessel
      diameter increased from 4.7 +/- 1.8 to 13.4 +/- 2.4 mm (P < 0.001), and the
      pressure gradient improved from 41 +/- 25 to 9 +/- 11 mm Hg (P < 0.001). Higher
      initial gradient and smaller balloons were associated with a final stent diameter
      of <14 mm (P = 0.030 and 0.046). Jailed vessels occurred in 49% of stents with
      abnormal angiographic flow in 18/55. Six repeat catheterizations resulted in
      complications, including the one procedural death. CONCLUSION: Stents implants
      for PA stenoses provide effective improvement in vessel caliber in the long-term.
      Although repeat interventions are necessary, this procedure reduces RV pressure
      and provides an important alternative to surgery for residual PA obstruction.

PMID- 20146311
TI  - Use of a low-profile, compliant balloon for percutaneous aortic valvuloplasty.
AB  - OBJECTIVES: To determine the safety and immediate efficacy after balloon aortic
      valvuloplasty (BAV) with a new, low-profile balloon. BACKGROUND: BAV has a
      continuing role in the management of high-risk patients with severe aortic
      stenosis (AS). BAV with traditional noncompliant balloons requires a large
      femoral arteriotomy and is associated with high rates of access site
      complications. METHODS: We retrospectively reviewed medical records of 20
      consecutive patients undergoing BAV for severe AS. Retrograde transfemoral BAV
      was performed with a low-profile, compliant valvuloplasty balloon. Before and
      after BAV, transaortic gradients were measured invasively and by
      echocardiography, and aortic valve area (AVA) calculated. Access site
      complications, functional class and survival were recorded. RESULTS: Patients
      were 79 +/- 12 years old and had an estimated mortality from open aortic valve
      replacement of (12.5 +/- 9.6)%. By catheterization, mean aortic gradient fell
      from 44 +/- 15 to 29 +/- 10 mm Hg (P < 0.001) and AVA increased from 0.63 +/-
      0.22 to 0.89 +/- 0.33 cm(2) (P < 0.001). New York Heart Association functional
      class improved from 3.5 +/- 0.7 to 2.7 +/- 0.8. Procedural mortality was 0%.
      There were no vascular complications or significant worsening of aortic
      regurgitation. CONCLUSION: Transfemoral BAV using a low-profile compliant balloon
      is feasible with acceptable immediate results and safety.

PMID- 20146312
TI  - Dissection, occlusion, and spasm; myths involving sheathless guide catheters.

PMID- 20146313
TI  - Long-term complication after LM bifurcation treatment.
AB  - Two months after left anterior descending (LAD) artery and left circumflex (LCx)
      artery bare metal stent implantation, a proliferative subocclusive in-stent
      restenosis in LCx coronary with severe LM coronary (LM) involvement developed.
      The present clinical case describes a simplified strategy for unprotected LM
      percutaneous coronary intervention using two bioabsorbable biolimus-eluting
      stents without involvement of the LAD coronary using an "L" technique.

PMID- 20146314
TI  - Cardiovascular computed tomographic angiography evaluation following unsuccessful
      invasive angiography: the clinical utility of 3D volume rendering.
AB  - In an appropriate clinical setting, cardiac CT angiography (CCT) can be used as a
      safe and effective noninvasive imaging modality for defining coronary arterial
      anatomy by providing detailed three-dimensional anatomic information that may be
      difficult to obtain with invasive coronary angiography (ICA). We present a
      patient where coronary angiography by ICA was unsuccessful and where the
      subsequent CCT proved to be very useful in providing us relevant information.

PMID- 20146316
TI  - Transcatheter aortic valve implantation by left subclavian access in the presence
      of a patent LIMA to LAD graft.
AB  - We present a case of successful implantation of the Corevalve aortic
      bioprosthesis via the left subclavian artery in a patient with a patent internal
      mammary graft to the left anterior descending artery. This unusual choice of
      access, in the presence of adequate caliber femoral arteries, was justified by
      the presence of mobile thrombi in the abdominal aorta. The risk of thrombus
      dislodgement and subsequent major cholesterol embolization was deemed higher than
      the risk of coronary ischemia due to the large caliber sheath required for
      transcatheter aortic valve implantation. This case shows that presence of a LIMA
      to LAD graft is not an absolute contraindication for homolateral subclavian
      access and that the procedure is feasible and relatively safe provided that
      certain rules are followed.

PMID- 20146315
TI  - Bailout stenting for critical coarctation in premature/critical/complex/early
      recoarcted neonates.
AB  - BACKGROUND: Surgical repair of critical coarctation can be problematic in
      premature, critical, complex, or early postoperative neonates. OBJECTIVES: We
      aimed to review our experience with stent implantation to defer urgent surgery to
      an elective time. METHODS: Fifteen neonates with severe aortic coarctation: five
      premature-hypotrophic (1,400-2,000 g), six critical and complex cardiac
      malformation, four early (1 day [0-2 days]; median [range]) after surgical
      coarctectomy or complex arch reconstruction. Bare coronary stents (diameter 4.0
      [3.5-5.0] mm; length 10 [8-16] mm) were used. Stents were removed surgically
      depending on clinical needs. RESULTS: Adequate aortic flow was obtained in 15
      patients. The femoral artery was preserved in 13/15 patients. Two deaths occurred
      before stent removal and were nonprocedure related. In patients with simple
      stented coarctation, the stent was removed after 2.8 [0.2-5.0] months. In complex
      cardiac malformation, stents were finally removed 3.0 [0.2-78] months after
      implantation. SURGICAL TECHNIQUE: simple coarctectomy end-to-end in eight,
      extensive arch patch reconstruction in four. One patient is awaiting stent
      removal. The final maximum systolic velocity (cw-Doppler) across the aortic arch
      was 1.7 [1.2-2.5] m/sec. CONCLUSIONS: In premature/critical/complex neonates with
      severe coarctation, bailout stenting followed by early or late surgical
      coarctectomy appears a promising concept.

PMID- 20146317
TI  - Endovascular treatment of Angio-Seal-related limb ischemia--primary results and
      long-term follow-up.
AB  - OBJECTIVES: To investigate primary success rates and long term follow-up of
      endovascular treatment of AngioSeal-related limb ischemia. BACKGROUND: Current
      knowledge on optimal therapy of ischemic complications following application of
      AngioSeal is limited. METHODS: A single-center prospectively maintained database
      was retrospectively interrogated and AngioSeal-related complications requiring
      endovascular treatment over an 8-year-time period was identified. RESULTS:
      Fifteen patients fulfilling the inclusion criteria were identified, resulting in
      an approximated incidence of 0.26% of all devices implanted at our institution.
      In all cases, the complication was managed successfully in the absence of
      complications. Eleven patients were treated with balloon angioplasty (PTA) and
      four with stent implantation because of suboptimal PTA results. Twelve patients
      were available for noninvasive vascular follow-up examination for a median time
      of 40 months postinterventionally. Only two patients needed a second intervention
      consisting of balloon angioplasty due to symptomatic restenosis. At final follow
      up all patients were asymptomatic with no relevant restenosis. CONCLUSION:
      Endovascular treatment for AngioSeal-related limb ischemia with or without stent
      implantation results in an excellent immediate and long-term clinical and
      hemodynamic outcome.

PMID- 20146318
TI  - Novel application of the "CART" technique for endovascular treatment of external
      iliac artery occlusions.
AB  - We report the novel application of the Controlled Antegrade and Retrograde
      subintimal Tracking technique for the endovascular treatment of occlusions of the
      external iliac artery (EIA). We hypothesized that this technique would limit the
      extent of subintimal dissection to the length of the EIA occlusion, thus
      preserving patency of the internal iliac artery proximally and the circumflex
      iliac artery distally and minimizing the length of stent required to treat the
      occlusion, including the length of stent placed in the common femoral artery. The
      technical execution and clinical experience with this technique is reported.

PMID- 20146319
TI  - Is the left anterior descending artery really absent?--a decisive input from
      coronary CT angiography.
AB  - This case report emphasizes the importance of coronary CT angiography (CTA) as a
      backup imaging modality in patients with suspected coronary anomalies and
      difficult cannulation, during invasive coronary angiography by catheterization
      (Cath). In this patient, the numerous cannulation attempts during Cath failed to
      identify a left anterior descending artery (LAD) leading to the diagnosis of
      absent LAD. CTA was done for further clarification, which easily visualized LAD
      originating from a separate ostium at the left sinus of Valsalva finalizing the
      diagnosis as absent left main artery with dual left coronary ostia.

PMID- 20146320
TI  - Paravalvular regurgitation one year after transcatheter aortic valve
      implantation.
AB  - OBJECTIVES: The aim of this study was to assess the natural history of
      paravalvular regurgitation at 1 year in patients undergoing TAVI. BACKGROUND: The
      immediate incidence of paravalvular regurgitation is estimated to be between 65
      and 85% following transcatheter aortic valve implantation (TAVI). There is
      limited data as to whether this deteriorates during follow-up. METHODS: Forty-six
      patients were recruited from a TAVI programme at our institute. All patients
      underwent an assessment of prosthetic valve function periprocedurally with
      aortography and immediately postprocedurally with transthoracic echocardiography.
      Twenty-one patients with a median age was 83 (66-91) years of whom 14 were male
      reached 1 year follow-up, 13 of whom were available for repeat transthoracic
      echocardiography. RESULTS: The incidence of paravalvular regurgitation
      immediately following TAVI was 86%. Of them 57% had < or = mild regurgitation and
      29% had > mild regurgitation. At 1 year the incidence of paravalvular
      regurgitation was 77%. 54% had < or = mild regurgitation and 34% > mild
      regurgitation. No patient had severe regurgitation. The degree of regurgitation
      reduced in 6 (46%), stayed the same in 3 (23%), and increased in 4 (31%) of
      patients. CONCLUSIONS: Patients undergoing TAVI have an immediate postprocedural
      risk of regurgitation of 86%. In the majority of cases the degree of paravalvular
      CoreValve regurgitation is mild, and remains stable in 70% of patients during
      medium term follow-up.

PMID- 20146321
TI  - The SYNTAX score revisited: a reassessment of the SYNTAX score reproducibility.
AB  - OBJECTIVES: To reassess the reproducibility of the SYNTAX score. BACKGROUND: The
      SYNTAX score appears to have an important role to play in the evaluation of
      patients with complex coronary artery disease undergoing revascularisation.
      However, the calculation of the SYNTAX score relies on the subjective assessment
      of lesions using coronary angiography, and therefore is subject to intra-and
      inter-observer variability. METHODS: The SYNTAX score was calculated in 100
      patients randomly selected from the SYNTAX trial, on two occasions 8 weeks apart,
      by a team made up of three interventional cardiologists. The weighted kappa
      values were compared with values obtained 1 year previously, when core lab
      analysts assessed the intra-observer reproducibility amongst the same patient
      cohort. RESULTS: The mean +/- standard deviation difference in SYNTAX score was
      2.1 +/- 7.6. The respective weighted kappa values for the number of lesions,
      bifurcation lesions, ostial lesions, and total occlusions were 0.62, 0.36, 0.66,
      and 0.91 compared with 0.59, 0.41, 0.63, and 0.82 in the previous core lab
      assessment. The weighted kappa for the intra-observer reproducibility of the
      SYNTAX score grouped into deciles was 0.54, and according to the terciles < or =
      22, >22-< or = 32, >32 was 0.51 both indicating a moderate level of agreement
      beyond the level of chance. In the previous assessment, the comparative kappa
      values were 0.45 and 0.53. CONCLUSIONS: The SYNTAX score has moderate intra
      observer reproducibility when assessed by a team of three interventional
      cardiologists, which is consistent with a prior evaluation performed by core lab
      analysts. The scoring of bifurcation lesions remains the main source of
      inconsistency.

PMID- 20146322
TI  - Stent expansion of stretch Gore-Tex grafts in children with congenital heart
      lesions.
AB  - OBJECTIVE: To evaluate the efficacy and safety of expanding vascular shunt grafts
      beyond original nominal diameter using stents. METHODS: Bench testing confirmed
      the expandability of 3.5 mm and 4.0 mm vascular Gore-Tex stretch grafts. A
      retrospective analysis included eleven systemic to pulmonary artery shunts with
      diminished flow which were stented with the aim of increasing the original
      nominal diameter of the shunts. RESULTS: During bench testing, the grafts could
      be expanded to 4.5 mm and 5.8 mm, respectively. Fourteen stents were implanted in
      11 stretch grafts a median of 18.9 months (3.2; 21.6 months) after shunt surgery.
      There was a median increase in diameter of 1.4 mm (0.9; 1.7 mm) [P = 0.001, 95%
      CI: 0.47; 1.7) from original nominal to final stented diameter of the shunts with
      a median gain of 28%. A simultaneous improvement in saturations from a median of
      73% (66; 77%) to 87% (84; 89%) [P = 0.015; 95% CI: 3; 22] was observed. No
      complications were experienced during the procedures. CONCLUSION: In our limited
      experience, stretch Gore-Tex vascular grafts can be safely expanded beyond
      nominal diameters using high pressure vascular stents. This leads to improvement
      in saturation and pulmonary blood flow. It allows the clinician to tailor
      pulmonary flow in relation to pulmonary artery size and growth, ensuring best
      possible timing for the next surgical procedure.

PMID- 20146323
TI  - "The chimney graft"-a simple technique for endovascular repair of complex
      juxtarenal abdominal aortic aneurysms in no-option patients.
AB  - Endovascular aneurysm repair (EVAR) has developed as a less invasive alternative
      to open surgery for patients with abdominal aortic aneurysms. However, patients
      with very short infrarenal necks require complex surgical open repair, which is
      associated with increased mortality and morbidity. The risk of complex open
      repair may be prohibitive in high-risk patients. Thus, modifying the technique of
      EVAR may be required in such patients to successfully exclude aneurysms. An
      alternative that can be used in these patients is the so-called "chimney graft"
      technique. We report two cases where the chimney graft technique was used with
      good immediate results.

PMID- 20146324
TI  - Coil occlusion of a subclavian mycotic aneurysm.
AB  - We report the first successful application of nonferromagnetic embolization coils
      for endovascular exclusion of a mycotic right subclavian artery aneurysm. A 58
      year-old woman presented with acute cervical pain and a pulsatile mass in the
      right supraclavicular fossa under antibiotic medication for subacute infectious
      endocarditis. Diagnostic work-up including duplex sonography, digital subtraction
      angiography, and magnetic resonance imaging demonstrated a saccular aneurysm of
      the extrathoracic right subclavian artery. As an alternative to open surgery or
      stent-graft repair, this pathology was electively treated by transcatheter coil
      embolization. No neurological deficit or ischemic symptoms were noted during 9
      months clinical follow-up. Multislice computed tomography scan revealed complete
      occlusion of the mycotic aneurysm 6 months after the interventional procedure.
      Transcatheter closure with Inconel embolization coils is a cost-effective and
      safe therapeutic option in patients with mycotic aneurysm originating from the
      subclavian artery.

PMID- 20146325
TI  - Combined mechanical and pharmacological approach to a thrombus-containing lesion.
AB  - Distal embolization during primary percutaneous coronary intervention for acute
      myocardial infarction is associated with impaired myocardial perfusion and poor
      outcome. Numerous pharmacological and mechanical strategies have been proposed to
      prevent and treat distal embolization. A successful combined mechanical and
      pharmacological approach to a large thrombus-containing lesion in patients with
      acute coronary syndrome is described. A review of the current literature
      regarding the drugs and devices available for the prevention and treatment of
      large thrombus burden has also been performed.

PMID- 20146326
TI  - Safety of drug eluting stents in patients on chronic anticoagulation using long
      term single antiplatelet treatment with clopidogrel.
AB  - BACKGROUND: Use of triple therapy with aspirin, clopidogrel, and anticoagulants
      significantly increases bleeding, thus drug eluting stents (DES) are usually
      avoided in patients requiring anticoagulation. We tested use of DES vs. BMS using
      a long-term therapy with clopidogrel only and anticoagulants in this group of
      patients. METHODS: We enrolled 165 consecutive patients, 79 receiving DES (age 67
      +/- 9 years, 84% with atrial fibrillation) and 86 receiving bare metal stents
      (BMS) (age 70 +/- 11 years, 71% with atrial fibrillation). All patients received
      aspirin + clopidogrel + oral anticoagulants for 4 weeks, then aspirin was stopped
      and clopidogrel was continued during the 12-month follow-up. Primary end point
      was the combined incidence of major adverse coronary events and major bleedings.
      RESULTS: Incidence of the primary endpoint was 10.1% in patients with DES and
      26.7% in patients with BMS (P = 0.01). There was a large difference in incidence
      of target vessel revascularization (8.1% for DES, 23.3% for BMS, P = 0.01),
      whereas incidence of myocardial infarction (3.8% in DES vs. 8.1% in BMS) and
      major bleeding (1.3% vs. 2.3%, respectively) were not significantly different.
      There were no cases of stent thrombosis. On multivariate Cox regression analysis,
      the only factor associated with a reduced risk of the primary endpoint was use of
      DES (hazard ratio 0.35 with 95% confidence interval 0.14-0.85, P = 0.02).
      CONCLUSIONS: Results of our cohort study suggest that use of DES associated with
      a treatment with clopidogrel only may be safe and significantly reduce the need
      for new revascularization in patients requiring chronic anticoagulation.

PMID- 20146327
TI  - Percutaneous coronary intervention using a virtual 3-Fr guiding catheter.
AB  - BACKGROUND: We have recently reported a novel percutaneous coronary intervention
      (PCI) system using a hydrophilic-coated sheathless guiding catheter (Virtual 3
      Fr, Medikit, Tokyo, Japan), which provides us with less invasive angioplasty and
      a puncture site injury equivalent to a conventional 3-Fr introducer sheath. Here,
      we report the initial results of PCI using this novel system. METHODS: A total of
      36 coronary artery lesions of 27 patients were treated by using a virtual 3-Fr
      PCI system. Procedural outcomes of virtual 3-Fr PCI were retrospectively
      evaluated. RESULTS: The mean age was 73.0 +/- 8.7 years (range, 46-84 years), and
      15 were men (56%). Access sites included the radial artery in 18 patients (67%),
      the brachial artery in eight patients (30%), and the femoral artery in 1 patients
      (4%). Among 36 lesions, seven were chronic total occlusions, and a virtual 3-Fr
      PCI was successful in 33 lesions (92%). Among the successfully treated 33
      lesions, coronary stents were deployed in 32 (97%), and intravascular ultrasound
      examination was performed in 19 (58%). Hemostasis was achieved immediately after
      PCIs in all cases. No access-site related complications including radial artery
      occlusion were observed. CONCLUSIONS: The performance of a virtual 3-Fr PCI
      system appears to be comparable to one using a regular 5-Fr guiding catheter
      while the puncture-site damage remains equivalent to that of a 3-Fr introducer
      sheath. Virtual 3-Fr PCI may have a potential to serve as a minimally invasive
      strategy for the treatment of coronary artery diseases.

PMID- 20146328
TI  - Transaortic transcatheter aortic valve implantation: a novel approach for the
      truly "no-access option" patients.
AB  - OBJECTIVES: The aim of this study was to test the safety and efficacy of the
      retrograde, minimally invasive, "transaortic" approach of transcatheter aortic
      valve implantation (TAVI) using the Medtronic CoreValve prosthesis (Medtronic,
      Minneapolis) as an alternative minimally invasive surgical access route.
      BACKGROUND: TAVI is today recognized as an established percutaneous technique for
      patients with severe aortic valve stenosis (AS). However, as the number of
      patients screened for TAVI increases, many are found with absolutely no option
      for peripheral artery access. METHODS: A new method of TAVI access, described as
      "transaortic" was performed in two patients A CoreValve prosthesis was implanted
      via the "transaortic" route. The patients were a 93- and a 84-year-old woman,
      both with severe PAOD. After a ministernotomy the ascending aorta was directly
      punctured. At the end, the access site was surgically sutured with the
      prepositioned sutures. The patients were at all times "off-pump" (beating heart
      procedure) and without IABP. RESULTS: TAVI was successful in both cases, leading
      to a fall in the transvalvular gradient and there were no cases of mortality,
      stroke or myocardial infarction. The patients were extubated directly after the
      procedure, mobilized after 4 days, and were discharged home after 7 and 9 days.
      CONCLUSIONS: In the rare occasion, where due to anatomical reasons transfemoral
      TAVI is not feasible, a minimally invasive "transaortic" approach, as described,
      provides an alternative option. This is especially true when the transapical
      route is not suitable (annulus >25 mm or contraindication to lateral
      thoracotomy).

PMID- 20146330
TI  - Pilot study to estimate the accuracy of mouth self-examination in an at-risk
      group.
AB  - BACKGROUND: Mouth self-examination (MSE) is a possible method of detecting oral
      cancer early. This study aimed to determine whether those at risk of developing
      oral cancer are able to correctly detect potentially malignant oral lesions via
      MSE. METHODS: Participants (53 smokers aged over 45 years) received an oral
      mucosal examination by the dentist and then performed MSE after education through
      a self-read leaflet. The dentist and participant both recorded the presence and
      absence of potentially malignant oral lesions. RESULTS: The prevalence of
      potentially malignant oral lesions was 22%. The sensitivity of MSE was 33% and
      the specificity was 54%. MSE had a positive predictive value of 17% and a
      negative predictive value of 73%. CONCLUSION: The at-risk group were poor at
      correctly identifying the presence or absence of potentially malignant oral
      lesions. A leaflet may be an ineffective training tool to aid self-identification
      of potentially malignant oral lesions.

PMID- 20146329
TI  - Single-stage repair of subglottic stenosis using the radial forearm free flap as
      a vascularized carrier.
AB  - BACKGROUND: We present a case report of a patient with history of subglottic
      carcinoma who underwent chemoradiation and subsequently developed subglottic
      stenosis (SGS). METHODS AND RESULTS: She was treated with an anterior cricoid
      split maintained by septal cartilage wrapped in a partially deepithelialized
      radial forearm free flap (RFFF). To date, with a follow-up of 6 months, the
      patient has been fully decannulated and has not experienced airway collapse or
      any other complications. CONCLUSIONS: Upper airway reconstruction using a single
      stage autogenous cartilage graft wrapped in a vascularized carrier is a real
      option for those patients with extensive SGS in the setting of an irradiated and
      devascularized tissue bed.

PMID- 20146332
TI  - Correlation between reduced expression of the spindle checkpoint protein BubR1
      and bad prognosis in tonsillar carcinomas.
AB  - BACKGROUND: Spindle checkpoint proteins such as Mad2 and BubR1 are important for
      chromosome segregation during mitosis. The aim of the present study was to
      examine their possible impact on prognosis in tonsillar carcinomas and their
      relation to clinical variables, the prevalence of human papillomavirus (HPV), p53
      status, and Ki-67 positivity. METHODS: We examined the expression of Mad2 and
      BubR1 by immunohistochemistry on tissue microarrays from 105 patients with
      tonsillar carcinomas. RESULTS: BubR1 and Mad2 were both expressed in tonsillar
      carcinomas. Expression of BubR1 was a significant prognostic factor in univariate
      survival analysis. In multivariate analyses, BubR1 was a significant prognostic
      factor together with stage, age, and HPV status p < .01), whereas Mad2 did not
      show any significant correlations. CONCLUSION: We have shown that BubR1
      expression is a novel and strong prognostic factor in tonsillar carcinomas,
      giving additional information to the TNM stage and other known prognostic
      factors.

PMID- 20146333
TI  - Misses and near-misses after postoperative radiation therapy for head and neck
      cancer: Comparison of IMRT and non-IMRT techniques in the CT-simulation era.
AB  - BACKGROUND: The purpose of this study was to compare the patterns of failure
      focusing on the distribution of local-regional recurrence among patients treated
      postoperatively with conventional radiotherapy (RT) and intensity-modulated
      radiotherapy (IMRT) for head and neck cancer. METHODS: The records of 130
      patients treated by surgery and postoperative radiation therapy for squamous cell
      carcinoma of the head and neck were reviewed. Seventy-eight patients (60%) were
      treated using conventional RT and 52 patients (40%) were treated using IMRT.
      RESULTS: The 3-year estimates of local-regional control were 70% and 73% among
      patients treated by conventional RT and IMRT, respectively (p = .33). Among the
      local-regional recurrences in the IMRT group, 9 were in-field recurrences
      occurring within the physician-designated clinical target volume (CTV), and 4
      were marginal recurrences involving the contralateral neck adjacent to the spared
      parotid gland (3 patients) and the retropharyngeal/retrostyloid lymph node region
      (1 patient). CONCLUSION: Our study showed that conventional RT and IMRT result in
      similar rates of local-regional control. The implications for CTV design are
      discussed herein.

PMID- 20146334
TI  - Incidence and prediction of major cardiovascular complications in head and neck
      surgery.
AB  - BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) usually
      have a history of tobacco and alcohol abuse. These 2 intoxications not only are
      main oncologic risk factors but also show a strong causal relationship with
      certain comorbid conditions. Examples are coronary artery disease, stroke, renal
      dysfunction, and heart failure, which are all proven major risk factors for an
      adverse postoperative outcome after stressful noncardiac surgery. Preoperative
      identification of these conditions could lead to preventive measures in patients
      with HNSCC that undergo extensive surgery. Preventing morbidity and mortality is
      of medical and economical importance. METHODS: All comorbidity of 135 consecutive
      patients with HNSCC that underwent extensive oncologic and reconstructive surgery
      as the first form of treatment between 2001 and 2007 was investigated. Based on
      these data, a Lee Cardiac Risk Index (LCRI) Score and an overall Adult
      Comorbidity Evaluation (ACE-27) severity score were calculated. The predictive
      value of these scores and the American Society of Anesthesiologists' (ASA)
      classification toward major cardiovascular complication development were
      investigated. Major cardiovascular complications were defined as: cardiac death,
      nonfatal myocardial infarction, heart failure, and cardiac arrhythmias. The
      impact of these complications on duration of hospitalization, medical costs, and
      short-term mortality (defined as death within 6 months after primary tumor
      diagnosis) were investigated as well. The cardioprotective effect of
      preoperatively prescribed beta blockers and statins are discussed. RESULTS:
      Twenty-two patients developed 23 major cardiovascular complications (16.3%). In
      univariate and multivariate analyses, a higher LCRI score was associated with an
      increased risk for major cardiovascular complications, as was an age >70 years
      (all values of p < .01). The area under the receiver operating characteristics
      (ROC) curve (AUC) for the multivariate model was 0.84, indicating a good
      prognostic value. In univariate and multivariate analysis, a higher ACE-27 score
      was associated with an increased risk for major cardiovascular complications, as
      was as age >70 years (all values of p < .01). The AUC for this model was 0.84,
      indicating a performance similar to that of the LCRI score model. No
      statistically significant results were found for the ASA scores (p = .38).
      Preoperative beta-blocker use showed a significant cardioprotective function in
      univariate analysis, whereas statins did not. The mean duration of
      hospitalization was prolonged by 7 days in patients with a major cardiovascular
      complication. In economic terms, this means a cost increase of at least 3500
      euros. None of the patients died during admission because of a major
      cardiovascular complication. The short-term mortality rate was 11.1%, but no
      specific cardiovascular cause of death was reported in these patients.
      CONCLUSIONS: Prevention of major complication occurrence after extensive HNSCC
      surgery is of medical and economic importance. Our results show that the ACE-27
      and the LCRI are suitable instruments for preoperative major cardiovascular
      complication risk assessment. Addition of the variable age >70 years shows an
      improvement in predictive value of both instruments. Because of its simplicity we
      advise the implementation of the LCRI into preoperative HNSCC screening
      protocols. We advise the exploration of low-dose long-acting beta blockers as a
      preventive treatment strategy.

PMID- 20146335
TI  - Tumor-induced osteomalacia originating from the temporal bone: a case report.
AB  - BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare clinical entity in which
      secondary osteomalacia is induced by tumor-related products. Fibroblast growth
      factor 23 (FGF-23) mRNA is overexpressed in the tumor tissue, leading to impaired
      reabsorption of phosphorus in the renal tubules and hypophosphatemia. Curative
      treatment is considered to be total resection of the tumor. METHODS AND RESULTS:
      A 53-year-old woman had experienced systemic bone pain and muscle weakness for
      several years. She had refractory hypophosphatemia and marked elevation of serum
      FGF-23 level. Whole body imaging eventually revealed a hypervascular mass in the
      right temporal bone, leading to a diagnosis of TIO. She underwent skull-base
      surgery after embolization of the tumor. After the en bloc resection, FGF-23
      became undetectable, phosphate reabsorption normalized, and all symptoms
      resolved. CONCLUSIONS: We discuss the clinical features and treatment options for
      this rare disease.

PMID- 20146336
TI  - Induction of laryngeal cancer cell death by Ent-11-hydroxy-15-oxo-kaur-16-en-19
      oic acid.
AB  - BACKGROUND: Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F) is known to exhibit
      antitumor activity, but its mechanism is not completely understood. 5F has not
      been tested in laryngeal cancer. METHODS: Two laryngeal cancer cell lines were
      treated with 5F. Cell death was analyzed by MTT [3-(4,5-dimethylthiozol-2-yl)-2,5
      diphenyltetrazolium bromide] and Annexin V assay. Nuclear factor kappa beta (NF
      kappaB)- and apoptosis-related molecules were examined. RESULTS: 5F induced
      laryngeal cancer cell death in a dose-dependent manner. The Annexin V assay and
      the measurement of cleavage of procaspase-3 and poly(ADP-ribose) polymerase
      demonstrated that the 5F-induced cell death was mainly apoptotic. 5F slightly
      reduced the basal level of NF-kappaB, but significantly suppressed the inducible
      NF-kappaB by reducing its transcriptional activity, protecting its inhibitory
      subunit IkappaBalpha from degradation, and suppressing its level in the nucleus.
      5F also inhibited pro-proliferative and anti-apoptotic molecules but promoted pro
      apoptotic Bax. CONCLUSIONS: 5F induces apoptosis of laryngeal cancer cells by
      inhibiting NF-kappaB activation/induction, suppressing pro-proliferative and anti
      apoptotic molecules, and promoting pro-apoptotic Bax.

PMID- 20146337
TI  - Complete stent dislodgement after successful implantation--a rare case.
AB  - A successfully deployed stent is normally stable in position and unlikely to be
      dislodged from the coronary artery. We report a case of complete stent
      dislodgement after successful implantation in a patient with recent anterior
      myocardial infarction (AMI). Coronary angulation, a highly calcified coronary
      artery, an under-deployed stent, and the process of rewiring contributed to this
      unexpected event. Fortunately, no unwanted complication occurred as a consequence
      of this event.

PMID- 20146338
TI  - Mechanical valve dysfunction after percutaneous perimitral leak closure: salvage
      by percutaneous occluder retrieval.
AB  - Percutaneous closure of perivalvular regurgitation may be complicated by
      prosthetic valve impingement and dysfunction. We describe a patient with two
      perimitral defects who developed severe mitral stenosis due to mitral leaflet
      impingement after percutaneous implantation of three amplatzer muscular
      ventricular septal defect occluder devices. The largest amplatzer occluder device
      was successfully snared with restoration of normal prosthetic valve motion.

PMID- 20146339
TI  - Differences in voriconazole trough plasma concentrations per oral dosages between
      children younger and older than 3 years of age.
AB  - The relationship between trough plasma concentrations and daily doses of
      voriconazole was retrospectively analyzed in < or = 18-year-old children because
      optimal oral voriconazole dosages for children, especially <2 years of age, is
      unknown. We demonstrated that the relationship changed around the age of 3 years,
      and that children <3 years of age required higher optimal daily doses with
      greater variations compared with those for older children, resulting in
      complicated optimal dose adjustments. Therefore, plasma concentration monitoring
      and individual dose adjustments are recommended for optimal and less toxic
      voriconazole treatments, especially for <3-year-old children, although additional
      studies are needed to validate this approach.

PMID- 20146340
TI  - Outcome of sinonasal melanoma: clinical experience and review of the literature.
AB  - BACKGROUND: Primary sinonasal malignant melanoma (SNMM) is a rare clinical
      entity. There is neither a classification nor a staging system nor an evidence
      based treatment concept established. Our objective was to find potential risk
      factors predicting the outcome. METHODS: Twenty-five patients with histologically
      confirmed SNMM were consecutively included and retrospectively analyzed. Staging
      methods were nasal endoscopy, CT, MRI, and positron emission tomography (PET)
      scan. Patients were selected for a curative or palliative concept. All patients
      had postoperative follow-up with control-MRI at 3 and 6 months. Restaging was
      performed when local recurrence occurred. RESULTS: Nineteen patients underwent
      primary surgery with curative intention; in 16 cases with tumor free margins.
      Thirteen patients (68%) had transnasal endoscopic surgery, 4 lateral rhinotomy,
      and 2 transfacial approach with orbital exenteration. Six patients (32%) had
      palliative therapy and 7 patients (37%) had adjuvant radiotherapy. Despite
      radical operations, 6 patients (37%) showed local recurrence and 8 patients (50%)
      developed distant metastasis. In 2 patients with incomplete surgery, regional
      metastasis was noted. The median disease-free interval was 18 months, and the
      median overall survival rate was 23 months. CONCLUSION: SNMMs of the ethmoid and
      maxillary sinuses have a worse prognosis than other localizations in the nasal
      cavity; infiltration into the skull base, orbit, or facial soft tissue correlates
      with a very poor outcome corresponding to the palliative situations. Furthermore,
      local recurrence insinuates aggressive disease with short survival rate. A main
      difference from its cutaneous counterpart seems to be a primary tendency to
      hematogenic spread. Further research is needed to confirm these findings.

PMID- 20146341
TI  - Comparison of conventional and cutting balloon angioplasty for congenital and
      postoperative pulmonary vein stenosis in infants and young children.
AB  - BACKGROUND: Pulmonary vein stenosis (PVS) is a rare and often lethal condition in
      children. The optimal treatment for congenital and postoperative PVS is unknown.
      METHODS AND RESULTS: We compared outcomes of conventional balloon angioplasty
      performed for PVS from 1999 to 2003 against cutting balloon angioplasty performed
      from 2004 to 2007. A total of 100 previously undilated pulmonary veins in 54
      patients were studied: 48 veins dilated with conventional balloons and 52 with
      cutting balloons. Acute results included significantly reduced gradients and
      increased lumen diameters with both treatments. Acutely, cutting balloon
      angioplasty and conventional angioplasty yielded similar relative reduction of
      the PVS gradient (median 78% vs. 63%, P = 0.08) and increase in lumen diameter
      (median 77% vs. 59%, P = 0.07). There was one procedural death of a critically
      ill infant, and four cardiac arrests, but no adverse events necessitating
      surgical intervention. Survival free from reintervention was poor in both groups,
      and shorter in the cutting balloon group (73% at 1 month, 11% at 6 months, and 4%
      at 1 year) than in the conventional angioplasty group (77% at 1 month, 35% at 6
      months, and 23% at 1 year; P = 0.01). CONCLUSIONS: Both conventional and cutting
      balloon angioplasty were effective at decreasing gradient and increasing lumen
      size acutely in patients with congenital and postoperative PVS, but
      reintervention was common with both treatments. Both methods of angioplasty
      provided limited benefit, and neither was curative for this complex disease.

PMID- 20146342
TI  - Histology of highly echolucent regions in optical coherence tomography images
      from two patients with sirolimus-eluting stent restenosis.
AB  - We report on two patients with sirolimus-eluting stent (SES) restenosis lesions
      who showed highly echolucent regions by optical coherence tomography (OCT) and
      who could be assessed histologically after removal by directional coronary
      atherectomy (DCA). One restenosis lesion had a bilayer structure of hyperechoic
      outer layers and highly echolucent inner layers on OCT images and histologically
      exhibited myxomatous neointima tissue in the highly echolucent regions; another
      restenosis case showed patchy and highly echolucent regions throughout the layers
      and its histology revealed fibrin thrombosis. We should be aware that patterns of
      echolucent on OCT images may have various histology. OCT allows the visualization
      of fine lesions that conventional intravascular ultrasound (IVUS) cannot provide.
      The OCT images of drug-eluting stent restenosis lesions often show echolucent
      regions [Shuzoh et al., EuroInterv 2006;1:484]. However, no histological study of
      the lesions has been reported to date. Here we report on two patients with SES
      restenosis lesions that showed highly echolucent regions by OCT and that could be
      assessed histologically after removal by DCA.

PMID- 20146343
TI  - Pathologic evaluation of sentinel lymph nodes in oral squamous cell carcinoma.
AB  - BACKGROUND: The objective of this study was to determine the relative efficacy of
      different methods of pathologic evaluation of sentinel lymph nodes. METHODS: In
      this prospective study, sentinel nodes were evaluated for occult metastasis using
      frozen section, imprint-cytology, hematoxylin-eosin staining, serial step
      sectioning (SSS) with hematoxylin-eosin, and immunohistochemistry (IHC).
      Metastases were classified into macrometastasis (>2.0 mm), micrometastasis (0.2
      mm-2.0 mm), isolated tumor cells (<0.2 mm). RESULTS: Occult metastasis was
      detected in 20 of 80 patients. Frozen section and imprint cytology identified
      metastasis in 10 of 20 patients, hematoxylin-eosin stain in 13 patients; SSS
      upstaged the disease in a further 7 patients (9%). Frozen section detected
      macrometastasis in 7 of 8 cases but failed to detect smaller metastases (missed
      micrometastasis in 4 of 7 and isolated tumor cells in 5 of 5). SSS upstaged the
      disease by 10%, and sensitivity and negative predictive value of SSS with
      hematoxylin-eosin stain were 90% and 97%, respectively. CONCLUSION: Frozen
      section and imprint cytology are not effective in identifying occult metastasis.
      IHC and SSS are required to identify micrometastasis and isolated tumor cells.

PMID- 20146344
TI  - Pyostomatitis vegetans as an oral manifestation of Crohn's disease in a pediatric
      patient.

PMID- 20146345
TI  - Proximal protection in recanalization of totally occluded saphenous vein grafts
      in acute coronary syndrome.
AB  - Percutaneous treatment of old, degenerated saphenous vein grafts (SVG) is
      associated with a high likelihood of major adverse cardiac events. When an acute
      coronary syndrome (ACS) develops in a patient with old SVG, fresh thrombus may
      superimpose on an old, degenerative atheroma: a sudden increase in the athero
      thrombotic burden ensues with consequent, frequent total occlusion of the lumen.
      In this scenario, transluminal recanalization of the graft is usually associated
      with the highest chance of distal embolization and no-reflow and positioning of
      an embolic protection device (EPD) is almost mandatory. However, distal EPD are
      difficult to place when the vessel is totally occluded and do not completely
      avoid distal embolization. We report two cases of totally occluded SVG in
      patients admitted for ACS that were recanalized with the aid of a proximal EPD
      system with angiographic and clinical success.

PMID- 20146346
TI  - Leptin-like immunoreactivity in the muscle of juvenile sea bass (Dicentrarchus
      labrax).
AB  - The mammalian hormone, leptin, is mainly synthesized in adipose tissue along with
      other tissues. Leptin plays a role in numerous processes such as in the control
      of food intake, homeostasis, immune function and reproduction. In this study, we
      detected and localized leptin immunoreactivity to the muscle of early juvenile
      sea bass (Dicentrarchus labrax) by Western blot analysis and
      immunohistochemistry. A leptin immunopositive band with a molecular weight of
      approximately 16 kDa, corresponding to mammalian leptin, was identified in trunk
      skeletal muscle homogenate. Furthermore, leptin immunopositive cells were
      detected in the endomysium of skeletal muscular fibers. These cells showed
      immunostained cytoplasmic granules and roundish and oval nuclei. The most intense
      immunostaining was observed in the endomysial space among the superficial red
      muscular fibers of the trunk. These findings suggest that in early juvenile sea
      bass, leptin is mostly produced by skeletal muscles. Therefore, during the
      developmental stage lacking adipose tissue, skeletal muscles can be considered an
      important source of leptin. As already suggested in mammals, we can hypothesize
      the potential roles of leptin not only in energy expenditure for muscle
      contraction but also during muscle differentiation and growth.

PMID- 20146347
TI  - Polylactide nanoparticles containing stably incorporated cyanine dyes for in
      vitro and in vivo imaging applications.
AB  - Stably incorporating fluorescent molecules to polymeric nanoparticles (NPs) or
      micelles can facilitate the prolonged tracking of these drug-delivery vehicles in
      vitro and in vivo. However, incorporation of fluorescent molecules, usually
      charged and thereby water-soluble, through the encapsulation strategy to
      hydrophobic polymer matrices is challenging. The encapsulated fluorescent agents
      are also subject to rapid release when the polymeric NPs are exposed to
      biological media. To address this issue, we developed Cy5-conjugated polylactide
      (Cy5-PLA) NPs through Cy5/(BDI)ZnN(TMS)2 [(BDI) = 2-((2,6
      diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene]-mediated
      ring-opening polymerization of lactide (LA) followed by nanoprecipitation. This
      process allows for covalent conjugation of Cy5 to PLA with quantitative
      incorporation efficiency and formulation of Cy5-PLA NPs with controlled particles
      size (approximately 100 nm). As much as 80% of Cy5 was still present in the Cy5
      PLA NPs after theses NPs were incubated in PBS at 37 degrees C for 12 days. Cy5
      PLA NPs were conjugated to the A10 RNA aptamer that binds to the prostate
      specific membrane antigen (PSMA). The resulting Cy5-PLA/aptamer NPs were found to
      only bind to and get internalized by LNCaP and canine prostate adenocarcinoma
      cells (PSMA-positive), but not to PC3 cells (PSMA-negative). The Cy5-PLA NPs were
      administered to balb/c mice intravenously and found to have excellent signals
      with low-background fluorescence in various organs.

PMID- 20146348
TI  - The administration of nonmetabolizable glucose analogues fails to suppress the
      development of glycogen autophagy in newborn rat hepatocytes.
AB  - The effects of parenteral administration of glucose, 3-methylglucose (3MG), or 2
      deoxyglucose (2DG) on the glycogen autophagy were studied in the newborn rat
      liver using electron microscopy and biochemical methods. The administration of
      glucose resulted in hyperglycemia and prevented the mobilization of hepatocytic
      glycogen. It also prevented the development of autophagic vacuoles in general and
      inhibited the glycogen-degrading activity of acid alpha-1,4-glucosidase. The
      nonphosphorylated and not further metabolized glucose analog 3MG also produced
      hyperglycemia, but increased acid glucosidase. Pretreating the newborns with the
      beta-adrenergic blocker propranolol inhibited the effects of 3MG. The
      phosphorylated but not fully metabolized glucose analog 2DG produced similar
      effects. The administration of xylitol to the newborns already treated with 2DG,
      suppressed acid glucosidase. The results of this and our previous studies suggest
      that glucose must be metabolized beyond its phosphorylation step to inhibit acid
      glucosidase activity.

PMID- 20146349
TI  - Microhardness and SEM after CO(2) laser irradiation or fluoride treatment in
      human and bovine enamel.
AB  - BACKGROUND: It remains uncertain as to whether or not CO(2) laser is able to
      hinder demineralization of enamel. The possibility to use bovine instead of human
      teeth on anticariogenic studies with laser has not yet been determined. PURPOSE:
      To compare the ability of CO(2) laser and fluoride to inhibit caries-like lesions
      in human enamel and to test whether a similar pattern of response would hold for
      bovine enamel. STUDY DESIGN: Ninety-six enamel slabs (2 * 2 * 4 mm) (48 from
      bovine and 48 from human teeth) were randomly distributed according to surface
      treatment (n = 12): CO(2) laser, 5% sodium fluoride varnish (FV), 1.23%
      acidulated phosphate fluoride (APF) gel, or no treatment (control). Specimens
      were subjected to a 14-day in vitro cariogenic challenge. Microhardness (SMH) was
      measured at 30 MUm from the surface. For ultrastructural analysis, additional 20
      slabs of each substrate (n = 5) received the same treatment described earlier and
      were analyzed by SEM. RESULTS: ANOVA and Tukey test ascertained that CO(2) laser
      promoted the least mineral loss (SMH = 252(a)). Treatment with FV resulted in the
      second highest values (207(b)), which was followed by APF (172(c)). Untreated
      specimens performed the worst (154(d)). SEM showed no qualitative difference
      between human and bovine teeth. APF and control groups exhibited surfaces covered
      by the smear layer. A granulate precipitate were verified on FV group and fusion
      of enamel crystals were observed on lased-specimens. CONCLUSIONS: CO(2) laser may
      control caries progression more efficiently than fluoride sources and bovine
      teeth may be a suitable substitute for human teeth in studies of this nature.

PMID- 20146350
TI  - Image processing techniques in a preliminary morphometric characterization of
      corneal epithelium by scanning electron microscopy.
AB  - Several processing techniques of digital images allowed us to quantify the
      percentage of cell surface covered by microprojections (microvilli or
      microplicae) (SCM), the adhesion between epithelial cells by the parameter
      intercellular junctions (IJ), the size (cell area), shape (cell shape) and shade
      (cell shade) of cells on the corneal epithelium of nine rabbits. The data were
      analyzed and the epithelial cells were classified into three groups by cluster
      analysis. Assuming the representativeness of the sample, our findings suggest
      that for a normal corneal epithelium, 80% of the cells could show SCM >41%, and
      IJ >0.98 (being one a cell to cell junction without disruptions). Standard
      deviations of cell shade lower than 21 gray levels could indicate a tendency to
      lose the cell shade mosaic. Normal corneas could show a majority of cells (54
      69%) included in group 2 with smaller mean size (80% of cells with cell area <242
      MUm(2)), higher SCM (80% of cells with SCM >44.83%), polygonal mean shape and
      brighter shade. Group 1 (15-30% of cells) could show a larger mean size (80% of
      cells with cell area >494 MUm(2)), lower SCM (although 80% of cells with SCM
      >32.61%), circular mean shape and darker electron reflex. Group 3 could display a
      medium mean size, higher SCM (similar to group 2), circular mean shape (similar
      to group 1), and brighter shade. These analyses could possibly be used to further
      assess the corneal response to ocular drugs, contact lens, and surgical
      procedures or to discriminate between pathology stages.

PMID- 20146351
TI  - In vivo high-resolution magnetic resonance skin imaging at 1.5 T and 3 T.
AB  - As a noninvasive modality, MR is attractive for in vivo skin imaging. Its unique
      soft tissue contrast makes it an ideal imaging modality to study the skin water
      content and to resolve the different skin layers. In this work, the challenges of
      in vivo high-resolution skin imaging are addressed. Three 3D Cartesian sequences
      are customized to achieve high-resolution imaging and their respective
      performance is evaluated. The balanced steady-state free precession (bSSFP) and
      gradient echo (GRE) sequences are fast but can be sensitive to off-resonance
      artifacts. The fast large-angle spin echo (FLASE) sequence provides a sharp
      depiction of the hypodermis structures but results in more specific absorption
      rate (SAR). The effect of increasing the field strength is assessed. As compared
      to 1.5 T, signal-to-noise ratio at 3 T slightly increases in the hypodermis and
      almost doubles in the dermis. The need for fat/water separation is acknowledged
      and a solution using an interleaved three-point Dixon method and an iterative
      reconstruction is shown to be effective. The effects of motion are analyzed and
      two techniques to prevent motion and correct for it are evaluated. Images with
      117 x 117 x 500 microm(3) resolution are obtained in imaging times under 6 min.

PMID- 20146352
TI  - Multiple-mouse MRI with multiple arrays of receive coils.
AB  - Compared to traditional single-animal imaging methods, multiple-mouse MRI has
      been shown to dramatically improve imaging throughput and reduce the potentially
      prohibitive cost for instrument access. To date, up to a single radiofrequency
      coil has been dedicated to each animal being simultaneously scanned, thus
      limiting the sensitivity, flexibility, and ultimate throughput. The purpose of
      this study was to investigate the feasibility of multiple-mouse MRI with a phased
      array coil dedicated to each animal. A dual-mouse imaging system, consisting of a
      pair of two-element phased-array coils, was developed and used to achieve
      acceleration factors greater than the number of animals scanned at once. By
      simultaneously scanning two mice with a retrospectively gated cardiac cine MRI
      sequence, a 3-fold acceleration was achieved with signal-to-noise ratio in the
      heart that is equivalent to that achieved with an unaccelerated scan using a
      commercial mouse birdcage coil.

PMID- 20146354
TI  - Precise conditional immortalization of mouse cells using tetracycline-regulated
      SV40 large T-antigen.
AB  - Cellular immortalization provides a way for expansion and subsequent molecular
      characterization of rare cell types. Ideally, immortalization can be achieved by
      the reversible expression of immortalizing proteins. Here, we describe the use of
      conditional immortalization based on a modified tetracycline-regulated system for
      the expression of SV40 large T-antigen in embryonic stem (ES) cells and mice. The
      modified system relies on a codon improved reverse tetracycline transactivator
      (irtTA) fused to the ligand-binding domain (LBD) of the androgen receptor (irtTA
      ABD) or of a mutated glucocorticoid receptor (irtTA-GBD*). Induction of T-antigen
      is conferred only after addition of two ligands, one to activate the LBD
      (mibolerone for irtTA-ABD or dexamethasone for irtTA-GBD*) and one to activate
      the tetracycline transactivator (doxycycline). In ES cells, changes in gene
      expression upon large T induction were limited and reversible upon deinduction.
      Similarly, expression of T-antigen was very tightly regulated in mice. We have
      isolated and expanded bone marrow mesenchymal stem cells that could be
      genetically manipulated and maintained their differentiation properties after
      several passages of expansion under conditions that induce the expression of
      large T-antigen.

PMID- 20146355
TI  - Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and
      cardiomegaly.
AB  - Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder presenting with
      an elfin-like face, supravalvular aortic stenosis, a specific cognitive
      behavioral profile, and infantile hypercalcemia. We encountered two WBS patients
      presenting with infantile spasms, which is extremely rare in WBS. Array
      comparative genomic hybridization (aCGH) and fluorescent in situ hybridization
      (FISH) analyses revealed atypical 5.7-Mb and 4.1-Mb deletions at 7q11.23 in the
      two patients, including the WBS critical region and expanding into the proximal
      side and the telomeric side, respectively. On the proximal side, AUTS2 and CALN1
      may contribute to the phenotype. On the telomeric side, there are two candidate
      genes HIP1 and YWHAG. Because detailed information of them was unavailable, we
      investigated their functions using gene knockdowns of zebrafish. When zebrafish
      ywhag1 was knocked down, reduced brain size and increased diameter of the heart
      tube were observed, indicating that the infantile spasms and cardiomegaly seen in
      the patient with the telomeric deletion may be derived from haploinsufficiency of
      YWHAG.

PMID- 20146357
TI  - Studying pressure denaturation of a protein by molecular dynamics simulations.
AB  - Many globular proteins unfold when subjected to several kilobars of hydrostatic
      pressure. This "unfolding-up-on-squeezing" is counter-intuitive in that one
      expects mechanical compression of proteins with increasing pressure. Molecular
      simulations have the potential to provide fundamental understanding of pressure
      effects on proteins. However, the slow kinetics of unfolding, especially at high
      pressures, eliminates the possibility of its direct observation by molecular
      dynamics (MD) simulations. Motivated by experimental results-that pressure
      denatured states are water-swollen, and theoretical results-that water transfer
      into hydrophobic contacts becomes favorable with increasing pressure, we employ a
      water insertion method to generate unfolded states of the protein Staphylococcal
      Nuclease (Snase). Structural characteristics of these unfolded states-their water
      swollen nature, retention of secondary structure, and overall compactness-mimic
      those observed in experiments. Using conformations of folded and unfolded states,
      we calculate their partial molar volumes in MD simulations and estimate the
      pressure-dependent free energy of unfolding. The volume of unfolding of Snase is
      negative (approximately -60 mL/mol at 1 bar) and is relatively insensitive to
      pressure, leading to its unfolding in the pressure range of 1500-2000 bars.
      Interestingly, once the protein is sufficiently water swollen, the partial molar
      volume of the protein appears to be insensitive to further conformational
      expansion or unfolding. Specifically, water-swollen structures with relatively
      low radii of gyration have partial molar volume that are similar to that of
      significantly more unfolded states. We find that the compressibility change on
      unfolding is negligible, consistent with experiments. We also analyze hydration
      shell fluctuations to comment on the hydration contributions to protein
      compressibility. Our study demonstrates the utility of molecular simulations in
      estimating volumetric properties and pressure stability of proteins, and can be
      potentially extended for applications to protein complexes and assemblies.

PMID- 20146356
TI  - Dynamic expression of a LEF-EGFP Wnt reporter in mouse development and cancer.
AB  - We have characterized a transgenic mouse line in which enhanced green fluorescent
      protein (EGFP) is expressed under the control of multimerized LEF-1 responsive
      elements. In embryos, EGFP was detected in known sites of Wnt activation,
      including the primitive streak, mesoderm, neural tube, somites, heart, limb buds,
      mammary placodes, and whisker follicles. In vitro cultured transgenic embryonic
      fibroblasts upregulated EGFP expression in response to activation of Wnt
      signaling by GSK3beta inhibition. Mammary tumor cell lines derived from female
      LEF-EGFP transgenic mice treated with the carcinogen 7, 12
      dimethylbenz[a]anthracene (DMBA) also express EGFP. Thus, this transgenic line is
      useful for ex vivo and in vitro studies of Wnt signaling in development and
      cancer.

PMID- 20146358
TI  - Abstracts of the Seventy-Ninth Annual Meeting of the American Association of
      Physical Anthropologists. April 14-17, 2010. Albuquerque, New Mexico, USA.

PMID- 20146362
TI  - Crystal structure of a triacylglycerol lipase from Penicillium expansum at 1.3 A
      determined by sulfur SAD.

PMID- 20146363
TI  - Structure of human CLIC3 at 2 A resolution.

PMID- 20146365
TI  - Inhaled versus systemic antibiotics and airway inflammation in children with
      cystic fibrosis and Pseudomonas.
AB  - RATIONALE: Inhaled tobramycin has been shown to transiently clear Pseudomonas
      from lower airways in early cystic fibrosis (CF), but does not markedly reduce
      lung inflammation, a key factor in disease progression. OBJECTIVE: Test the
      hypothesis that systemic antibiotics are more effective than inhaled antibiotics
      for reducing lower airways inflammation. METHODS: Clinically stable CF children
      with recent Pseudomonas were randomized to receive 4 weeks of inhaled tobramycin
      or 2 weeks of systemic antibiotics (intravenous ceftazidime and tobramycin).
      Bronchoalveolar lavage fluid was obtained just before and 4-6 weeks after
      treatment. The primary outcome was change in % neutrophils in lavage fluid.
      RESULTS: Fifteen subjects (inhaled = 6, systemic = 9) completed the protocol.
      Three Systemic Group subjects could not have central venous access established
      and were treated with oral ciprofloxacin (plus inhaled tobramycin) for 2 weeks as
      an alternative "systemic" regimen, per protocol. Groups were well matched in age,
      markers of disease severity, and initial % neutrophils. The Systemic Group showed
      a modest median change in percent neutrophils (-7%) which was not statistically
      significant compared to inhaled (+5.4%, P = 0.07). However, the Systemic Group
      had significantly greater reductions in total cells (-50% vs. -3%, P < 0.01) and
      neutrophils (-74% vs. -10%, P = 0.02) per ml lavage fluid. Both groups had
      reduced bacterial quantity after treatment, but there was no significant
      difference between groups. CONCLUSIONS: In clinically stable children with CF,
      systemic antibiotics result in greater short-term reduction in lower airways
      inflammation than inhaled antibiotics.

PMID- 20146366
TI  - Motivational interviewing for adherence problems in cystic fibrosis.
AB  - This review focuses on adherence in cystic fibrosis (CF), and the factors known
      to influence it. In particular, it discusses the importance of effective
      communication in clinical settings and considers the evidence for the
      effectiveness of motivational interviewing (MI), to increase adaptation and
      adherence in physical health and CF. The review also contains an overview of the
      key concepts of MI, its' practice in medical settings and recommendations on how
      to adopt MI techniques in the routine care of people with CF.

PMID- 20146367
TI  - Reversible airway obstruction in children with ataxia telangiectasia.
AB  - INTRODUCTION: Lung disease is a significant cause of the short life span of
      ataxia telangiectasia (A-T) patients. Objective lung function measurements are
      difficult to achieve in A-T. AIM: To assess lung function by spirometry in
      relation to the clinical characteristics of A-T patients followed up at the
      Israeli Ataxia Telangiectasia National Clinic. PATIENTS AND METHODS: Medical and
      spirometry data were collected from 27 A-T patients during 2004-2007. Laboratory,
      nutritional condition, mode of treatment, pulmonary status, and malignancies were
      assessed. The spirometry values FVC, FEV(1), FEV(0.5), FEF(25-75), PEF and time
      rise to peak flow were analyzed individually and values were compared to those of
      healthy age-matched children. RESULTS: Eleven patients (40.7%) were found to
      suffer from asthma according to clinical symptoms and response to
      bronchodilators. We found significant reduction in FEV(1) and FEV(0.5) (z-scores:
      -0.84 + or - 0.7 SD, -0.7 + or - 0.6 SD; P = 0.0014 and P = 0.003, respectively),
      in relation to healthy predicted values. FEF(25-75) was significantly lower than
      that in healthy children in 5 of 11 asthmatic patients. All 27 patients showed
      higher than healthy FEV(1)/FVC and FEV(0.5)/FVC ratios (z-scores 0.68 + or - 0.99
      SD, P < 0.0015, and 2.12 + or - 1.50 SD, P < 0.0015, respectively). The rise time
      to peak flow was three-fold longer than that of healthy children. CONCLUSION:
      Obstructive lung disease is common among A-T patients. Maximal peak flow
      reduction and prolonged rise time to peak flow may be the first signs of
      pulmonary involvement in these patients. Early treatment with anti-asthma
      therapy, bronchodilators, and steroids, may prevent further pulmonary
      deterioration and improve the prognosis of A-T patients.

PMID- 20146368
TI  - Low levels of exhaled nitric oxide are associated with impaired lung function in
      cystic fibrosis.
AB  - Fraction of exhaled nitric oxide (FENO) is often reduced in cystic fibrosis (CF).
      FENO at different expiratory flows can provide an indication of the site of
      nitric oxide production. The aim of this study was to examine whether NO
      parameters are related to overall (FEV(1)) or peripheral (lung clearance index,
      LCI, measured by multiple breath SF(6) washout) airway function and systemic
      inflammation in CF. Secondary aim was to compare alveolar NO and bronchial NO
      flux calculated by two different mathematical models, a linear and a nonlinear
      method. Thirty-five healthy and 45 CF children were recruited. FENO at 50 ml/sec
      (FENO(50)) and bronchial NO flux were lower in CF than controls, 9.5 (2.7-38.8)
      (median (range)) versus 12.4 (5.2-40.1) ppb, P = 0.029, and 391 (97-1772) versus
      578 (123-1993) (pl/sec), P = 0.036, respectively. No difference in alveolar NO
      was shown. The nonlinear method resulted in lower alveolar NO and higher
      bronchial flux, than the linear method, but the result was closely correlated in
      both groups. LCI was higher in CF than controls, 8.4 (6.5-12.9) versus 5.9 (5.1
      7.8), P < 0.001. FENO(50) was negatively correlated with LCI (r = -0.43; P =
      0.003) and positively correlated with FEV(1) (r = 0.42, P = 0.004) in CF.
      Alveolar NO correlated negatively with inflammatory markers: orosomucoid (r = 
      0.42, P = 0.005), platelets (r = -0.50, P < 0.001) and white blood cell count (r
      = -0.48, P = 0.001). In conclusion, FENO(50) and bronchial NO flux are reduced in
      young CF subjects and low FENO(50) is associated with overall and small airway
      obstruction. NO parameters derived from the different models were closely related
      but the values differed slightly.

PMID- 20146369
TI  - Serum myeloperoxidase in wheezing infants: no association with later asthma.

PMID- 20146370
TI  - Acid steatocrit determination is not helpful in cystic fibrosis patients without
      or with mild steatorrhea.
AB  - BACKGROUND: Most methods used for the assessment of severe steatorrhea in cystic
      fibrosis (CF) are sensitive. In fact, the tests show their usefulness in a
      borderline zone of the results. Yet, the existing data related to acid steatocrit
      (AS) are still contradictory. Therefore, in the present study we have aimed to
      assess CF patients without or with mild steatorhea (<10 g/day) and evaluate the
      applicability of AS in such a subset of patients. PATIENTS AND METHODS: In fifty
      five CF patients, AS, fecal fat concentration (FFC) and fecal fat excretion (FFE)
      in 1-day stool collection were assessed from one to three times (149 samples). In
      50 subjects, FFC, FFE, and AS were available for 3 subsequent days. It allowed
      for the calculations based upon 3-day fecal fat balance study. RESULTS: The
      correlations between FFE/FFC and AS based upon 1-day stool collection, although
      statistically significant, were rather weak (r = 0.208, P < 0.011; r = 0.362, P <
      0.000006, respectively). The correlations between FFE/FFC and AS based upon the 3
      day stool collection, although stronger, did not show values a linear
      relationship (r = 0.394, P < 0.005; r = 0.454, P < 0.001, respectively). With no
      regard to the cut-off level for AS (10% and 20%), sensitivity, specificity,
      negative, and positive predictive values in the determination of abnormal FFC and
      FFE were not satisfactory. The flow charts describing the accuracy of AS to
      determine FFE and FC revealed a high level of uncertainty. CONCLUSIONS: AS does
      not reflect in a reliable way FFE in CF patients without or mild steatorrhea. Its
      applicability in the assessment of FFC in such patients has therefore limited
      practical value.

PMID- 20146371
TI  - Effect of face mask dead volume, respiratory rate, and tidal volume on inhaled
      albuterol delivery.
AB  - INTRODUCTION: Pediatric patients often require metered-dose inhaler (MDI) with
      holding chamber (HC) to overcome lack of coordination when receiving inhaled
      therapy. In infants and young children unable to use a mouthpiece, it is
      necessary to use a mask interface. We compared the effect of varying mask static
      dead volume (SDV), respiratory rate (RR), and tidal volume (VT) on albuterol
      captured at the mouth opening (ACMO) in an in vitro model. METHODS: An
      Aerochamber Max(R) without and with three mask sizes (SDV of 10, 36, 85, and 200
      ml, respectively) was connected in series to a filter holder and breathing
      simulator. ACMO was measured at VTs = 36, 72, 145, and 290 ml and RR of 12 and
      24. Each experiment comprised 10 puffs run for six respiratory cycles each.
      Albuterol was quantified via spectrophotometry at 276 nm. A P-value of 0.05 was
      considered significant. RESULTS: Increasing VT increased ACMO (all SDVs and RRs).
      Adding SDV decreased ACMO, except for the small mask at VTs = 145 and 290 ml at
      RR = 12. Increasing SDV decreased ACMO, except at VT = 36 ml (all masks) and VT =
      72 ml (small = medium) at RR = 12 and VT = 36 ml (small = other and medium >
      large) at RR = 24. Increasing RR increased ACMO for all SDVs at VTs = 36 and 72
      ml, but not for VTs = 145 and 290 ml, except for no and large mask at VT = 145
      ml. CONCLUSION: In general, decreasing SDV, increasing VT, and increasing RR
      increase ACMO. Early transition from face mask to mouthpiece should be considered
      in children receiving albuterol via MDI with HC.

PMID- 20146372
TI  - Face masks for aerosols-there is more science...

PMID- 20146373
TI  - Application of variable-rate selective excitation pulses for spin labeling in
      perfusion MRI.
AB  - Arterial spin labeling offers great potential in clinical applications for
      noninvasive measurement of cerebral blood flow. Arterial spin labeling tagging
      methods such as the flow sensitive alternating inversion recovery technique
      require efficient spatial inversion pulses with high inversion accuracy and sharp
      transition zones between inverted and noninverted magnetization, i.e., require a
      high performance inversion pulse. This work presents a comprehensive comparison
      of the advantages offered by a variable-rate selective excitation variant of the
      hyperbolic secant pulse against the widely used conventional hyperbolic secant
      pulse and the frequency offset corrected inversion pulses. Pulses were compared
      using simulation and experimental measurement in phantoms before being used in a
      flow sensitive alternating inversion recovery-arterial spin labeling perfusion
      measurement in normal volunteers. Both the hyperbolic secant and frequency offset
      corrected inversion pulses have small variations in inversion profiles that may
      lead to unwanted subtraction errors in arterial spin labeling at a level where
      the residual signal is comparable to the desired perfusion contrast. The variable
      rate selective excitation pulse is shown to have improved inversion efficiency
      indicating its potential in perfusion MRI. The variable-rate selective excitation
      pulse variant also showed greatest tolerance to radiofrequency variation and off
      resonance conditions, making it a robust choice for in vivo arterial spin
      labeling measurement.

PMID- 20146375
TI  - Ventilation/perfusion imaging in a rat model of airway obstruction.
AB  - The global increase in asthma, chronic obstructive pulmonary disease, and other
      pulmonary diseases has stimulated interest in preclinical rat models of pulmonary
      disease. Imaging methods for study of these models is particularly appealing
      since the results can be readily translated to the clinical setting.
      Comprehensive understanding of lung function can be achieved by performing
      registered pulmonary ventilation and perfusion imaging studies in the same
      animal. While ventilation imaging has been addressed for small animals,
      quantitative pulmonary perfusion imaging has not been feasible until recently,
      with our proposed technique for quantitative perfusion imaging using multiple
      contrast-agent injections and a view-sharing radial imaging technique. Here, we
      combine the method with registered ventilation imaging using hyperpolarized (3)He
      in an airway obstruction rodent model. To our knowledge, this is the first
      comprehensive quantitative assessment of lung function in small animals at high
      spatial resolution. Standard deviation of the log (V/Q) is used as a quantitative
      biomarker to differentiate heterogeneity between the control and treatment group.
      The estimated value of the biomarker lies within the normal range of values
      reported in the literature. The biomarker that was extracted using the imaging
      technique described in this work showed statistically significant differences
      between the control rats and those with airway obstruction.

PMID- 20146376
TI  - Effect of rosuvastatin on cholestasis-induced hepatic injury in rat livers.
AB  - Recent studies reported that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)
      reductase inhibitors have pleotropic effects independent of their lipid-lowering
      properties. The present study was undertaken to determine whether treatment with
      rosuvastatin (RO) would be beneficial in a rat model of bile duct ligation (BDL).
      Animals were divided into three groups: a sham group (group I), a BDL group
      treated with vehicle (group II), and a BDL group treated with RO (10 mg/kg)
      (group III). Serum levels of total bilirubin, gamma-glutamyl transpeptidase,
      alanine aminotransferase, and aspartate aminotransferase decreased significantly
      in group III when compared to group II. Lipid peroxides and NO levels of group
      III were found to be significantly lower than those of group II. Antioxidant
      enzymes (superoxide dismutase, glutathione-S-transferase, and catalase) activity
      in liver tissues markedly decreased in group II, whereas treatment with RO
      preserved antioxidant enzyme activity. DT-diaphorase activity in group II was
      significantly higher than that in group III. The histopathological results showed
      multiple numbers of newly formed bile ductules with inflammatory cells
      infiltration in group II. These pathological changes were improved in group III.
      Our data indicate that RO ameliorates hepatic injury, inflammation, lipid
      peroxidation and increases antioxidant enzymes activity in rats subjected to BDL.
      RO may have a beneficial effect on treatment of cholestatic liver diseases.

PMID- 20146377
TI  - Heterologous expression, purification, and biochemical characterization of a
      greenbug (Schizaphis graminum) acetylcholinesterase encoded by a paralogous gene
      (ace-1).
AB  - Acetylcholinesterase is a critical enzyme in the regulation of cholinergic
      neurotransmission in insects. To produce Schizaphis graminum acetylcholinesterase
      1 for structure-function analysis, we constructed a recombinant baculovirus to
      infect Sf9 cells, which secreted the soluble protein at a final concentration of
      4.0 mg/L. The purified enzyme had an apparent M(r) of 70 and 130 kDa in the
      reducing and nonreducing SDS-polyacrylamide gels, respectively, indicating that
      it formed a dimer via an intermolecular disulfide bond. The fresh enzyme had a
      specific activity of 245 U/mg, which stabilized at a lower level (115 U/mg) in
      storage. The Michaelis constant and maximum velocity were 88.3 +/- 9.6 microM and
      133.2 +/- 1.6 U/mg for acetylthiocholine iodide, 113.9 +/- 12.5 muM and 106.4 +/-
      3.0 U/mg for acetyl(beta-methyl)thiocholine iodide, 68.9 +/- 7.8 microM and 76.7
      +/- 1.0 U/mg for propionylthiocholine iodide, and 201.1 +/- 21.0 microM and 4.4
      +/- 0.1 U/mg for S-butyrylthiocholine iodide, respectively. The IC(50) values (5
      min, room temperature) of ethopropazine, BW284C51, carbaryl, eserine, malaoxon,
      and paraoxon were 102, 1.66, 0.94, 0.20, 0.061, 0.016 microM, respectively. The
      bimolecular reaction constants (k(i)) were (6.50 +/- 0.40) x 10(4) for carbaryl,
      (1.00 +/- 0.16) x 10(5) for eserine, (4.70 +/- 0.13) x 10(5) for malaoxon, and
      (9.06 +/- 0.23) x 10(5) M(-1) min(-1) for paraoxon. The enzyme was also inhibited
      by one of its products, choline, at concentrations higher than 20 mM, suggesting
      that choline bound to an anionic site and regulated the enzymatic activity.

PMID- 20146378
TI  - Oral cleft defects and maternal exposure to ambient air pollutants in New Jersey.
AB  - BACKGROUND: Evidence links exposure to ambient air pollution during pregnancy,
      particularly gaseous pollutants and particulate matter, to an increased risk of
      adverse reproductive outcomes though the results for birth defects have been
      inconsistent. METHODS: We compared estimated exposure to ambient air pollutants
      during early pregnancy among mothers of children with oral cleft defects (cases)
      to that among mothers of controls, adjusting for available risk factors from
      birth certificates. We obtained ambient air pollutant data from air monitoring
      sites in New Jersey for carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3),
      sulfur dioxide (SO(2)), particulate matter <10 microm in aerodynamic diameter
      (PM10) and particulate matter <2.5 microm in aerodynamic diameter (PM2.5). We
      used values from the nearest monitor (within 40 km of the residence at birth) for
      controls, cleft lip with or without cleft palate (CLP) and cleft palate only
      (CPO). RESULTS: Based on logistic regression analyses for each contaminant and
      all contaminants together, there were no consistent elevated associations between
      selected air pollutants and cleft malformations. Quartile of CO concentration
      showed a consistent protective association with CPO (p < 0.01). For other
      contaminants, confidence intervals (95%) of the odds ratios for some quartiles
      excluded one. CLP showed limited evidence of an association with increasing SO(2)
      exposure while CPO showed weak associations with increasing O3 exposure.
      CONCLUSION: There was little consistent evidence associating cleft malformations
      with maternal exposure to ambient air pollutants. Evaluating particular
      pollutants or disease subgroups would require more detailed measurement of
      exposure and classification of cleft defects.

PMID- 20146379
TI  - Proteomics analysis of liver samples from puffer fish Takifugu rubripes exposed
      to excessive fluoride: an insight into molecular response to fluorosis.
AB  - Comparative proteomics was performed to identify proteins in the liver of
      Takifugu rubripes in response to excessive fluoride exposure. Sixteen fish were
      randomly divided into a control group and an experimental group. The control
      group was raised in soft water alone (F(-) = 0.4 mg/L), and the experimental
      group was raised in the same water with sodium fluoride at a high concentration
      of 35 mg/L. After 3 days, proteins were extracted from the fish livers and then
      subjected to two-dimensional polyacrylamide gel electrophoresis analysis. The
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) was applied to identify the proteins that were differentially
      expressed from the two groups of fish. Among an average of 816 and 918 proteins
      detected in the control and treated groups, respectively, 16 proteins were
      upregulated and 35 were downregulated (P < 0.01) in the fluoride-treated group as
      compared with those in the control group. Twenty-four highly differentially
      expressed proteins were further analyzed by MALDI-TOF/TOF-MS, and eight were
      identified by Mascot. These eight proteins include disulfide isomerase ER-60,
      4SNc-Tudor domain protein, SMC3 protein, Cyclin D1, and mitogen-activated protein
      kinase 10, as well as three unknown proteins. Consistent with their previously
      known functions, these identified proteins seem to be involved in apoptosis and
      other functions associated with fluorosis. These results will greatly contribute
      to our understanding of the effects of fluoride exposure on the physiological and
      biochemical functions of Takifugu and the toxicological mechanism of fluoride
      causing fluorosis in both fish and human.

PMID- 20146380
TI  - Upregulation of genes orchestrating keratinocyte differentiation, including the
      novel marker gene ID2, by contact sensitizers in human bulge-derived
      keratinocytes.
AB  - In the epidermis, keratinocytes are involved in physical and first-line immune
      protection of the host. In this study, we analyzed the molecular responses to
      certain contact sensitizers (2,4-dinitrochlorobenzene and NiSO(4)) and irritants
      (sodium dodecyl sulfate and benzalkonium chloride) in cultured human
      keratinocytes from the bulge region of a plucked hair follicle (bulge-derived
      keratinocytes [BDKs]) and compared these molecular responses to those with the
      human monocytic leukemia cell line, THP-1. The BDKs, individually established
      without invasive biopsies, showed high reactivity to these stimulants. As a
      primary response to the contact sensitizers, the NRF2-mediated signaling pathway
      was upregulated in BDKs and THP-1. The expression of IL1B and IL8 genes was not
      induced by the irritants but by the sensitizers in THP-1. However, the expression
      of the IL1B and IL8 genes was induced at higher levels by the irritants in BDKs
      than by the sensitizers. Many genes orchestrating keratinocyte differentiation,
      including ID2, were significantly upregulated in response to the sensitizers in
      BDKs but not those in THP-1. The use of the ID2 gene to discriminate between
      sensitizers and irritants might be effective as a novel marker for application
      during in vitro sensitization with BDKs.

PMID- 20146381
TI  - The involvement of hypophyseal-gonadal and hypophyseal-adrenal axes in arsenic
      mediated ovarian and uterine toxicity: modulation by hCG.
AB  - This study evaluated the involvement of hypophyseal-gonadal and hypophyseal
      adrenal axes as a possible mechanism of sodium arsenite toxicity in ovary and
      uterus by the coadministration of hCG. Subchronic treatment of 0.4 ppm of sodium
      arsenite/(100 g body weight day) via drinking water for seven estrous cycles
      significantly suppressed the plasma levels of leutinizing hormone, follicle
      stimulating hormone, and estradiol along with sluggish ovarian activities of
      Delta(5),3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid
      dehydrogenase followed by a reduction in gonadal tissue peroxidase activities in
      mature female rats at diestrous phase. Noticeable weight loss of the ovary and
      uterus along with prolonged diestrous phase and increased deposition of arsenic
      in the plasma and in these reproductive organs were also demonstrated following
      the ingestion of arsenic. Follicular atresia and thinning of the uterine luminal
      diameter were evident after sodium arsenite treatment. Effective protection of
      gonadal weight loss, suppressed ovarian steroidogenesis, and altered ovarian and
      uterine peroxidase activities were noticed when 1.0 IU hCG/(100 g body weight
      day) is given in arsenic-intoxicated rats. Normal estrous cyclicity was restored
      toward the control level after hCG coadministration, though the elimination of
      elementary arsenic from the plasma and gonadal tissues was impossible. A
      significant recovery in the restoration of ovarian and uterine histoarchitecture
      was prominent after hCG treatment. Adrenal hypertrophy and steroidogenic arrest
      of the adrenal gland along with altered level of brain monoamines in the midbrain
      and diencephalons following arsenic intoxication were also ameliorated after hCG
      coadministration.

PMID- 20146382
TI  - Peroneal artery perforator chimeric flap for reconstruction of composite defects
      in extremities.
AB  - Large bone defects of extremities, especially those associated with soft tissue
      defects, represent difficult reconstructive problems. Chimeric flap is a suitable
      option for reconstruction of complex bone and soft-tissue defects. In this
      report, we present the experience on use of the peroneal artery perforator
      chimeric flap for the reconstruction of complex bone and soft tissue defects in
      the extremities in 16 patients. The bone defects were located in the tibia in 8
      patients, in both tibia and fibula in 1 patient, in the ulna in 2 patients, in
      both ulna and radius in 2 patients, and the metatarsal bone in 3 patients. The
      flap was created with skin paddle and fibula bone segments based on independent
      perforators. The sizes of flap ranged from 8 x 6 to 20 x 11 cm(2), and the length
      of fibular grafts ranged from 6 to 22 cm. All flaps survived completely. Bone
      union was ultimately obtained in all cases at 5 to 11 months, while two cases
      suffered from stress fractures in 12 month and 18 month after operation,
      respectively, which eventually healed with external fixation treatment. The
      follow-up time ranged from 12 to 37 months. The definite bone hypertrophy was
      observed from X-ray at 18 months after operation. In conclusion, our results show
      that the peroneal artery perforator chimeric flap is a good option for
      reconstruction of complex bone and soft-tissue defects of extremities,
      particularly for those with three-dimensional defects and bone defects exceeding
      6 cm in length.

PMID- 20146383
TI  - Cold ischemia in microvascular breast reconstruction.
AB  - INTRODUCTION: A major drawback to microvascular free flap breast reconstruction
      is the length of operation-up to 9 hours or more for bilateral reconstruction.
      This takes a significant mental and physical toll on the surgical team, producing
      fatigue that may compromise surgical outcome. To facilitate the operation we have
      incorporated a period of cold ischemia of the flaps such that members of the
      surgical team can alternate a brief respite during the operation. METHODS: We
      retrospectively reviewed our series of microvascular free flap breast
      reconstructions performed over a four-year period in which cold ischemia of the
      flaps were induced. RESULTS: Seventy patients underwent free flap breast
      reconstruction with 104 flaps. Mean cold ischemia time for all flaps was 2 hours
      36 min. Average rest time per surgeon per case was 35 min. Complications included
      two total flap losses (1.9%), one partial flap loss (1.0%), one anastomotic
      thrombosis (1.0%), two hematomas (1.9%), three fat necrosis (2.9%), and two
      delayed healing (1.9%). Statistical analysis revealed that the probability of
      complications is inversely related to cold ischemia time (P = 0.0163).
      CONCLUSION: Cold ischemia facilitates breast reconstruction by allowing the
      surgical team to alternate breaks during the operation. This helps reduce surgeon
      fatigue and is well tolerated by the flap. Thus, we believe that the use of cold
      ischemia is safe and advantageous in microvascular breast reconstruction.

PMID- 20146384
TI  - Factors influencing survival of free-flap in reconstruction for cancer of the
      head and neck: a literature review.
AB  - Microvascular free tissue transfer is a reliable technique for head and neck
      reconstruction with success rates of 90-99%. Currently, there is no consensus
      concerning antithrombotic agents, antibiotics, or monitoring techniques.
      Therefore, the aim of this study was to review current literature dealing with
      microvascular free-tissue transfer and factors influencing the outcome. In
      addition to excellent microsurgical techniques, coupling devices are a promising
      new technique, but are not useful in all arteries. Antibiotics should be given in
      three doses, as a more lengthy dosage time seems to have no advantage. The risk
      for elderly patients can be best assessed by the American Society of
      Anesthesiologists (ASA) score, but early mobilization, including intense chest
      physiotherapy, is important. Anticoagulation can be considered in cases of small
      vessels, significant size mismatch, vein graft, or vessels of poor quality.
      Monitoring should be done hourly during the first 24 hours and then every 4 hours
      for the next 2 postoperative days.

PMID- 20146385
TI  - Collagen nerve protector in rat sciatic nerve repair: A morphometric and
      histological analysis.
AB  - Peripheral nerve repair is often complicated by fibroblastic scar formation,
      nerve dysfunction, and traumatic neuroma formation. Use of bio-absorbable
      protective wraps may improve outcomes of these repairs. This study histologically
      compared the incidence of neuroma formation, connective tissue proliferation, and
      axonal regrowth in transected rat sciatic nerves repaired with and without
      tubular collagen nerve sleeves. Twenty Sprague-Dawley rats underwent unilateral
      sharp sciatic nerve transection and microscopic nerve repair with four epineural
      sutures and were randomly treated with or without an encircling collagen nerve
      sleeve. Normal nerves from the contralateral sciatic nerve were also examined. At
      sacrifice three months later, the nerves were evaluated for traumatic neuroma
      formation, perineural scar formation, and morphometric analysis. Histological
      examination of normal and repaired nerves by a neuropathologist demonstrated
      healing, minimal Wallerian degeneration and no traumatic neuroma formation.
      Distal section analysis (nine nonwrapped, 10 wrapped), revealed no significant
      differences in total fascicular area, myelinated fibers per nerve, fiber density,
      myelin area per nerve, myelinated fiber diameter, axon diameter, myelin
      thickness, or G-ratio. Significantly greater (P = 0.005) inner epineural
      connective tissue formation was observed in nonwrapped nerves (0.62 mm(2) +/-
      0.2) versus wrapped nerves (0.35 mm(2) +/- 0.16). The ratio of connective tissue
      to fascicular area was larger in nonwrapped (1.08 +/- 0.26) versus wrapped nerves
      (0.63 +/- 0.22) (P < 0.001). This study demonstrated decreased inner epineural
      connective tissue formation with use of a collagen nerve wrap during primary
      repair of peripheral nerve transection in a rat sciatic nerve model.

PMID- 20146386
TI  - A new role for hygienic pad in the laboratory settings.

PMID- 20146388
TI  - Short-term effect of physiotherapy on variability of the lung clearance index in
      children with cystic fibrosis.
AB  - Multiple breath washout (MBW) for measuring the lung clearance index (LCI) has
      been proposed as a non-invasive tool for detecting early cystic fibrosis (CF)
      lung disease. The LCI is highly repeatable and reproducible in healthy subjects.
      In patients with CF, within-test variability is low. However, application of
      physiotherapy (PT) immediately preceding MBW may affect LCI variability in CF
      patients and thus interpretation of repeat measurements and treatment effects.
      Therefore, the aim of the present study was to prospectively assess the short
      term effect of PT on LCI in CF patients in order to address the question whether
      or not standardized timing of PT and MBW has to be considered when introducing
      MBW into clinical CF management. Twenty-seven out of 32 patients (5.7-15.9 years)
      with CF successfully performed two technically acceptable MBW tests with the
      EasyOne Pro, MBW Module (ndd, Switzerland) at intervals of 1(1/2) hr. Sixteen out
      of 27 received 30 min PT in between, whereas 11/27 did not.Repeatability
      expressed as intraindividual coefficient of variation (CV) was 6.1% pre-PT and
      6.5% post-PT. Mean difference (95% CI) of LCI between the two tests was -0.20 (
      0.51; 0.11). Reproducibility (SD) was 4.6% (3.1). Repeatability was 4.2% and 7.1%
      without intervention. Mean difference (95% CI) of LCI between 1st and 2nd test
      was 0.07 (-0.22; 0.35). Reproducibility (SD) was 2.6% (2.1).In conclusion, PT
      does not have a consistent effect on the LCI. Repeatability was slightly poorer
      than published for healthy subjects possibly reflecting variable mucus plugging,
      and, thus, variable trapped air in patients with CF. Reproducibility was good and
      independent on intervention. From our data, we conclude that timing of PT in
      relation to MBW can be ignored when designing study protocols or when
      interpreting longitudinal data and treatment effects.

PMID- 20146389
TI  - The diversity of FtsY-lipid interactions.
AB  - The bacterial signal recognition particle (SRP) receptor FtsY forms a complex
      with the SRP Ffh to target nascent polypeptide chains to the bacterial inner
      membrane. How FtsY interacts with lipids and associates to the membrane is
      unclear. Here, we show that vesicle binding leads to partial protection against
      proteolytic degradation and a change in secondary structure, which differs
      depending on whether the lipids are simple mixtures of zwitterionic and anionic
      lipids, mimics of Escherichia coli lipids, or lysolipids. Lipid binding alters
      the stability of FtsY. Thermal unfolding of FtsY in buffer shows two transitions,
      one occurring at approximately 60 degrees C and the other at approximately 90
      degrees C. The thermal intermediate accumulating between 60 and 90 degrees C has
      structural features in common with the state induced by binding to E. coli
      lipids. E. coli lipid extract induces a single transition around 70 degrees C,
      anionic lipids have no effect while cooperative unfolding is completely removed
      in lysolipids. Thus, the lipid environment profoundly influences the dynamic
      properties of FtsY, leading to three different kinds of FtsY-lipid interactions
      with different effects on structure, proteolytic protection, and stability, and
      is driven both by hydrophobic and electrostatic interactions. Trypsin digestion
      experiments highlight the central role of the N-domain in lipid contacts, whereas
      the A- and G-domains appear to play a more minor part.

PMID- 20146390
TI  - Insight into the stability of cross-beta amyloid fibril from molecular dynamics
      simulation.
AB  - Amyloid fibrils are considered to play causal roles in the pathogenesis of
      amyloid-related degenerative diseases such as Alzheimer's disease, type II
      diabetes mellitus, the transmissible spongiform encephalopathies, and prion
      disease. The mechanism of fibril formation is still hotly debated and remains an
      important open question. In this study, we utilized molecular dynamics (MD)
      simulation to analyze the stability of hexamer for eight class peptides. The MD
      results suggest that VEALYL and MVGGVV-1 are the most stable ones, then SNQNNY,
      followed by LYQLEN, MVGGVV-2, VQIVYK, SSTSAA, and GGVVIA. The statistics result
      indicates that hydrophobic residues play a key role in stabilizing the zipper
      interface. Single point and two linkage mutants of MVGGVV-1 confirmed that both
      Met1 and Val2 are key hydrophobic residues. This is consistent with the
      statistics analysis. The stability results of oligomer for MVGGVV-1 suggest that
      the intermediate state should be trimer (3-0) and tetramer (2-2). These methods
      can be used in stabilization study of other amyloid fibril.

PMID- 20146387
TI  - Lessons learned from a randomized trial of airway secretion clearance techniques
      in cystic fibrosis.
AB  - RATIONALE: Airway secretion clearance therapies are a cornerstone of cystic
      fibrosis care, however longitudinal comparative studies are rare. Our objectives
      were to compare three therapies [postural drainage and percussion: (postural
      drainage), flutter device (FD), and high frequency chest wall oscillation:
      (vest)], by studying (1) change in pulmonary function; (2) time to need for
      intravenous (IV) antibiotics, (3) use of pulmonary therapies, (4) adherence to
      treatment, (5) treatment satisfaction, and (6) quality of life. METHODS:
      Participants were randomly assigned to one of three therapies twice daily.
      Clinical outcomes were assessed quarterly over 3 years. RESULTS: Enrollment goals
      were not met, and withdrawal rates were high, especially in postural drainage
      (51%) and FD (26%), compared to vest (9%), resulting in early termination. FEV(1)
      decline, time to need IV antibiotics, and other pulmonary therapies were not
      different. The annual FEF(25-75%) predicted rate of decline was greater in those
      using vest (P = 0.02). Adherence was not significantly different (P = 0.09).
      Overall treatment satisfaction was higher in vest and FD than in postural
      drainage (P < 0.05). Health-related quality of life was not different. The rate
      of FEV(1) decline was 1.23% predicted/year. CONCLUSIONS: The study was ended
      early due to dropout and smaller than expected decline in FEV(1). Patients were
      more satisfied with vest and FD. The longitudinal decline in FEF(25-75%) was
      faster in vest; we found no other difference in lung function decline, taken
      together this warrants further study. The slow decline in FEV(1) illustrates the
      difficulty with FEV(1) decline as a clinical trial outcome.

PMID- 20146391
TI  - Trauma exposure and hypothalamic-pituitary- adrenal axis functioning in mentally
      healthy Dutch peacekeeping veterans, 10-25 years after deployment.
AB  - Hypothalamic-pituitary-adrenal (HPA) axis alterations have been found in veterans
      with posttraumatic stress disorder (PTSD). It is unclear whether trauma exposure
      during adulthood in the absence of psychopathology is also associated with HPA
      axis dysregulation. Thirty-six trauma-exposed peacekeepers, 23 nonexposed
      peacekeepers, and 25 nonexposed civilians, all without lifetime psychopathology
      were studied. Basal HPA-axis functioning was assessed with salivary cortisol
      samples obtained over 2 days. HPA-axis reactivity was assessed with the
      dexamethasone/corticotropin-releasing hormone test. Lower afternoon salivary
      cortisol levels were found in both veteran groups versus controls after
      adjustment for confounders. The authors concluded that this study does not
      support the idea that HPA-axis functioning is durably altered by trauma exposure
      during adulthood in men.

PMID- 20146392
TI  - VA mental health services utilization in Iraq and Afghanistan veterans in the
      first year of receiving new mental health diagnoses.
AB  - Little is known about mental health services utilization among Iraq and
      Afghanistan veterans receiving care at Department of Veterans Affairs (VA)
      facilities. Of 49,425 veterans with newly diagnosed posttraumatic stress disorder
      (PTSD), only 9.5% attended 9 or more VA mental health sessions in 15 weeks or
      less in the first year of diagnosis. In addition, engagement in 9 or more VA
      treatment sessions for PTSD within 15 weeks varied by predisposing variables (age
      and gender), enabling variables (clinic of first mental health diagnosis and
      distance from VA facility), and need (type and complexity of mental health
      diagnoses). Thus, only a minority of Iraq and Afghanistan veterans with new PTSD
      diagnoses received a recommended number and intensity of VA mental health
      treatment sessions within the first year of diagnosis.

PMID- 20146393
TI  - Combat-injured service members and their families: the relationship of child
      distress and spouse-perceived family distress and disruption.
AB  - Combat injury in military service members affects both child and family
      functioning. This preliminary study examined the relationship of child distress
      postinjury to preinjury deployment-related family distress, injury severity, and
      family disruption postinjury. Child distress postinjury was assessed by reports
      from 41 spouses of combat-injured service members who had been hospitalized at
      two military tertiary care treatment centers. Families with high preinjury
      deployment-related family distress and high family disruption postinjury were
      more likely to report high child distress postinjury. Spouse-reported injury
      severity was unrelated to child distress. Findings suggest that early
      identification and intervention with combat-injured families experiencing
      distress and disruption may be warranted to support family and child health,
      regardless of injury severity.

PMID- 20146394
TI  - Subject-specific water-selective imaging using parallel transmission.
AB  - Spectral-spatial excitation pulses are an efficient means of achieving water- or
      fat-only imaging and can be used in conjunction with a variety of pulse
      sequences. However, the approach lacks reliability since its performance is
      dependent on the homogeneity of the static magnetic field. Sensitivity to static
      magnetic field variation can be reduced by designing pulses with wider frequency
      stop bands, but these require longer pulse durations. In the proposed method,
      spectral-spatial pulses are optimized on a subject-dependent basis to take into
      account measured subject-specific static magnetic field variation. Extra control
      of the radiofrequency (RF) field from multichannel transmission is used to
      achieve this without increasing the length of the pulses. The method
      characterizes RF pulses using relatively few parameters and has been applied to
      abdominal imaging at 3 T with an eight-channel system. In a comparison of
      standard and subject-specific pulses on five healthy volunteers, the latter
      improved fat suppression in all subjects, with a reduction in RF power of 13% +/-
      6%. A forward model suggests that the mean flip angle in fat was reduced from
      0.72 degrees +/- 0.55 degrees to 0.12 degrees +/- 0.04 degrees for a 20 degrees
      excitation; uniformity of water excitation also improved, with the standard
      deviation divided by mean reduced from 0.26 +/- 0.05 to 0.16 +/- 0.05.

PMID- 20146395
TI  - How much do primary care givers know about tracheostomy and home ventilator
      emergency care?
AB  - Children on home mechanical ventilation are a high-risk population. How much do
      primary caregivers (PC) know about handling unexpected situations with
      tracheostomies or malfunction of their ventilators? To answer this, we
      prospectively studied the knowledge of 152 PC (108 parents and 44 nurses), using
      a 25-question survey regarding emergency situations at home. RESULTS: their mean
      score was 20.2 correct answers (81%). However, 96 PC (63%) did not know that the
      low pressure ventilator alarm would not sound if the tracheostomy tube
      decannulated while still connected to the ventilator. Seventy-nine PC (52%)
      failed to understand high pressure alarms sound and mucous plugging. Sixty-six PC
      (43%) did not know how much power a battery stored after the suction machine was
      fully charged. Sixty-one PC (40%) did not know when the low pressure or low
      minute volume alarm sounds. Fifty-six PC (37%) relied on the ventilator alarm to
      determine the presence of mucous plugs. There were no significant differences in
      the scores of PC who used continuous flow ventilators, nor in English-speaking PC
      versus Spanish-speaking PC. The experience of the PC did not make a difference in
      their knowledge of HMV emergency care. Having professional training did not pose
      an advantage in the score for nurses. We conclude that most PC had a good
      understanding of emergency care. We speculate that more in depth education on the
      technical aspects of ventilator alarms and tracheal mucous plugging may help to
      reduce or prevent emergencies of children on HMV.

PMID- 20146396
TI  - Brownian motion of polyphosphate complexes in yeast vacuoles: characterization by
      fluorescence microscopy with image analysis.
AB  - In the vacuoles of Saccharomyces cerevisiae yeast cells, vividly moving insoluble
      polyphosphate complexes (IPCs) <1 microm size, stainable by a fluorescent dye,
      4',6-diamidino-2-phenylindole (DAPI), may appear under some growth conditions.
      The aim of this study was to quantitatively characterize the movement of the IPCs
      and to evaluate the viscosity in the vacuoles using the obtained data. Studies
      were conducted on S. cerevisiae cells stained by DAPI and fluorescein
      isothyocyanate-labelled latex microspheres, using fluorescence microscopy
      combined with computer image analysis (ImageJ software, NIH, USA). IPC movement
      was photorecorded and shown to be Brownian motion. On latex microspheres, a
      methodology was developed for measuring a fluorescing particle's two-dimensional
      (2D) displacements and its size. In four yeast cells, the 2D displacements and
      sizes of the IPCs were evaluated. Apparent viscosity values in the vacuoles of
      the cells, computed by the Einstein-Smoluchowski equation using the obtained
      data, were found to be 2.16 +/- 0.60, 2.52 +/- 0.63, 3.32 +/- 0.9 and 11.3 +/-
      1.7 cP. The first three viscosity values correspond to 30-40% glycerol solutions.
      The viscosity value of 11.3 +/- 1.7 cP was supposed to be an overestimation,
      caused by the peculiarities of the vacuole structure and/or volume in this
      particular cell. This conclusion was supported by the particular quality of the
      Brownian motion trajectories set in this cell as compared to the other three
      cells.

PMID- 20146397
TI  - Lung transplantation in children with idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: Despite improved medical therapy, transplantation (Tx) represents the
      only option for end-stage pulmonary vascular disease. METHODS: Clinical data of
      children with idiopathic pulmonary arterial hypertension (IPAH) referred for Tx
      assessment between January 2002 and June 2007 were related to listing decision
      and outcome. RESULTS: Seven of the 14 children assessed for Tx were listed. Five
      were transplanted (lung Tx, n = 3; heart-lung Tx, n = 2) and two died on the
      waiting list. Mean age at diagnosis was 3.7 (0.4-9.5) years. Time from diagnosis
      to listing was 3.6 years (range 1.4-9.3). Children listed were in a worse
      functional class (WHO 3.5 vs. 2.5; P = 0.0006), had a lower SpO(2) on exercise
      (76.5% vs. 89%; P = 0.0001) and a shorter 6-min walk distance (154 m vs. 330 m; P
      < 0.01) than those not listed. Right ventricular function was worse in those
      listed (P = 0.03), as was pulmonary vascular resistance index (PVRI) on
      vasodilator testing (34 U m(2) vs. 14.6 U m(2); P = 0.03). Age at diagnosis and
      at assessment, weight, height, mean pulmonary artery pressure, baseline PVRI, B
      type natriuretic peptide, spirometry and resting-SO(2) did not differ between the
      two groups. For the five children transplanted, median waiting time was 81 days.
      Age at Tx was 5.4 years. After 2.8 years all transplanted children are alive with
      a good functional outcome. Two patients died on the active waiting list. All
      children considered too well for listing are still alive and stable on treatment.
      CONCLUSIONS: Outcome after transplantation in children with IPAH has been
      encouraging. Defining listing criteria for these patients remains a challenge.

PMID- 20146398
TI  - Respiratory syncytial virus infection outbreak among pediatric patients with
      oncologic diseases and/or BMT.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) has been reported to cause severe
      morbidity and mortality among cancer patients receiving chemotherapy with or
      without autologous/allogeneic hematopoetic stem cell transplantation (HSCT).
      There have been few reports describing the outcome of RSV infection specifically
      among pediatric oncology patients. METHODS: Two RSV infection outbreaks developed
      between February-April 2006 and January-March 2009 in hospitalized pediatric
      patients for various hemato-oncological diseases + or - HSCT. A survey of
      respiratory viruses was done using direct immunofluorescent antibody assay from
      nasopharyngeal washing aspirate. RESULTS: In two RSV infection outbreaks (2006
      and 2009), RSV antigen was detected in 6/30 patients. Five of six patients with
      RSV antigen were all treated with 0.2-0.4 g/kg intravenous immune globulin (IVIG)
      and specific antiviral therapy, oral ribavirin (20-25 mg/kg/day in three doses).
      Five patients recovered fully, although two were retreated due to recurrent (+)
      RSV antigen and respiratory symptoms within 2 weeks. We did not give oral
      ribavirin to one patient with (+) RSV antigen due to mild symptoms. All patients
      are alive and well. CONCLUSIONS: In contrast with the outcome of RSV infection in
      adult oncology patients, the mortality associated with RSV infection in pediatric
      oncology patients even in post bone marrow transplantation (BMT) period, is low
      when diagnosed and treated early enough. Oral ribavirin might be an option
      together with IVIG in the treatment of RSV especially when other forms of
      antivirals could not be obtained. This approach will make it possible to give the
      scheduled anti-neoplastic therapy on time.

PMID- 20146399
TI  - Factors associated with trauma and posttraumatic stress disorder among homeless
      youth in three U.S. cities: the importance of transience.
AB  - Homeless youth experience disproportionately high rates of trauma and
      posttraumatic stress disorder (PTSD). This study examined correlates of trauma
      and PTSD among homeless youth with a focus on the impact of homeless culture,
      substance addiction, and mental health challenges. Homeless youth (N = 146) from
      Los Angeles, California, Denver, Colorado, and St. Louis, Missouri, were
      recruited from organizations providing services to homeless youth using
      comparable methods. Results indicate that 57% of respondents had experienced a
      traumatic event and 24% met criteria for PTSD. A multinomial logistic regression
      model revealed greater transience, alcohol addiction, mania, and lower self
      efficacy predicted PTSD whereas trauma exposure was associated with alcohol
      addiction only. Findings have implications for screening and intervening with
      traumatized homeless youth across service settings.

PMID- 20146400
TI  - Site-directed mutagenesis of Asp853 in Pdr3p transcriptional activator from
      Saccharomyces cerevisiae.
AB  - The PDR3 gene encodes one of the main transcriptional activators involved in the
      control of multidrug resistance in the yeast Saccharomyces cerevisiae. Recently,
      it has been demonstrated that a specific D853Y mutation results in the loss of
      transactivation activity of Pdr3p and its conversion to multicopy suppressor of
      multidrug resistance. In this study, the Asp853 in Pdr3p was replaced by eight
      different amino acids and the function of mutated proteins was analysed.
      Different levels of complementation of cycloheximide hypersensitivity and
      expression of autoregulated PDR3 and its PDR5 target in the pdr1Deltapdr3Delta
      mutant strain, ranging from that of the wild-type to loss-of-function alleles,
      were observed in pdr3 mutants containing Pro, Glu, Arg, Asn, Ser, Leu, Phe, Ile
      or Tyr instead of Asp853 in Pdr3p. The introduction of the D853Y mutation into
      gain-of-function Pdr3p suppressed the transcription of the PDR3 and PDR5 genes
      and reduced both the rhodamine 6G efflux rate and the drug resistance level in
      corresponding double mutants. The results indicate that, while Pdr3p can tolerate
      several substitutions of Asp853, the occurrence of a hydrophobic amino acid at
      this position has an adverse effect on its function.

PMID- 20146401
TI  - Development and validation of a robust LC-MS-MS with atmospheric pressure
      chemical ionization for quantitation of carbazochrome sodium sulfonate in human
      plasma: application to a pharmacokinetic study.
AB  - A highly selective and sensitive liquid chromatography coupled with atmospheric
      pressure chemical ionization tandem mass spectrometry (LC-APCI-MS-MS) was
      developed and validated for the quantitation and pharmacokinetic study of
      carbazochrome sodium sulfonate in human plasma. Protein precipitation with 14%
      perchloric acid solution was selected for sample preparation, and amiloride
      hydrochloride was employed as an internal standard. The analytes were separated
      on a Hypersil ODS-2 column by a multiple-step linear gradient elution with a
      mobile phase consisting of 0.2% formic acid solution and methanol pumped at a
      flow rate of 1.0 mL/min. The determination was optimized and carried out with
      positive atmospheric pressure chemical ionization by selective reaction
      monitoring of the ion of m/z 148, the protonated thermodegraded fragment of the
      free acidic form of carbazochrome sodium sulfonate selected as the parent, and
      the ion of m/z 107 as the optimum collision induced dissociation (CID) product.
      The method was fully validated over a concentration range of 0.5-50 ng/mL, with
      the lower limit of quantitation of 0.5 ng/mL. The application of the LC-MS-MS
      method was demonstrated for the specific and quantitative analysis of
      carbazochrome sodium sulfonate in human plasma from a pharmacokinetic study in 24
      healthy male Chinese volunteers after a single oral administration of 90 mg
      carbazochrome sodium sulfonate capsules.

PMID- 20146402
TI  - The role of PaAAC1 encoding a mitochondrial ADP/ATP carrier in the biosynthesis
      of extracellular glycolipids, mannosylerythritol lipids, in the basidiomycetous
      yeast Pseudozyma antarctica.
AB  - Pseudozyma antarctica produces large amounts of the glycolipid biosurfactants
      known as mannosylerythritol lipids (MEL), which show not only excellent surface
      active properties but also versatile biochemical actions. A gene homologous with
      a mitochondrial ADP/ATP carrier was dominantly expressed in P. antarctica under
      MEL-producing conditions on the basis of previous gene expression analysis. The
      gene encoding the mitochondrial ADP/ATP carrier of P. antarctica (PaAAC1)
      contained a putative open reading frame of 954 bp and encodes a polypeptide of
      317 amino acids. The deduced translation product shared high identity of 66%,
      70%, 69%, 74%, 75% and 52% with the mitochondrial ADP/ATP carrier of
      Saccharomyces cerevisiae (AAC1), S. cerevisiae (AAC2), S. cerevisiae (AAC3),
      Kluyveromyces lactis (KlAAC), Neurospora crassa (NcAAC) and human (ANT1),
      respectively, and conserved the consensus sequences of all ADP/ATP carrier
      proteins. The gene expression by introducing a plasmid pUXV1-PaAAC1 into the
      yeast cells increased the MEL production. In addition, the expression of PaAAC1
      in which the conserved arginine and leucine required for ATP transport activity
      were replaced with isoleucine and serine, respectively, failed to increase MEL
      production. Accordingly, these results suggest that PaAAC1 encoding a
      mitochondrial ADP/ATP carrier should be involved in MEL biosynthesis in the
      yeast.

PMID- 20146403
TI  - From geek to chic.

PMID- 20146404
TI  - [Antistroke activity of Actoinvit (substance S-1) in experimental hemorrhagic
      stroke].
AB  - A model of hemorrhagic stroke (HS) (intracerebral posttraumatic hematoma) has
      been used to show that oral Actoinvit (substance S-1) in a daily dose of 500
      mg/kg for 7 days causes a steady-state antistroke effect. At the same time the
      major neurological parameters became lower and the total indices of orientative
      trying behavior improved 24 hours just after administration of the drug. Muscle
      tone, coordination of movements, and memory impairment recovered on days 7-14
      after the simulation of HS. The course use of the agent prevented death from HS
      in 80% of the animals.

PMID- 20146405
TI  - [Peripheral blood circulation in the skin and the regulatory mechanisms in the
      course of primary transmural myocardial infarction].
AB  - Laser Doppler flowmetry was used to study the indicators characterizing the
      peripheral blood circulation in the skin, regulatory mechanisms, and the
      compensatory capacities of the microcirculatory bed in 32 patients aged 45-60
      years in the course of primary transmural myocardial infarction during exercise
      tests. Significant disturbances of the mechanism responsible for regulating the
      peripheral blood circulation system and chiefly its active components were
      detected in the presence of adequate blood filling of microvessels. There was a
      drastic decrease in the reserves of skin microvascular endothelial activity
      during ionophoresis of sodium nitroprusside and acetylcholine, the maximum degree
      of disturbances being observed on day 10 of myocardial infarction development.

PMID- 20146406
TI  - [Evaluation of the protection efficiency of secretory antibodies in experimental
      Yersinia infection in guinea-pigs immunized with polyvalent vaccine against this
      infection].
AB  - The paper presents the results of experiments to elucidate the protection
      efficiency of secretory antibodies via parenteral and oral inoculation with
      pathogenic Yersinia in guinea pigs immunized with a polyvalent yersiniasis
      vaccine designed on the basis of the pseudotuberculosis microbial strain that
      synthesizes the F1 antigen of a plague microbe. Immunization of guinea pigs with
      the polyvalent yersiniasis vaccine protects experimental animals against
      pseudotuberculosis, intestinal yersiniasis, and plague infections.

PMID- 20146407
TI  - [The therapeutic and preventive effects of pectin in experimental renal failure].
AB  - The efficacy of an enterosorbent based on low-esterified pectin, activated
      charcoal, and polyphepan was evaluated in rats with experimental renal failure.
      Pectin was shown to be most effective. Its use causes increased daily diuresis
      and lower blood urine and creatinine levels in experimental animals. The findings
      have led to the conclusion that low-esterified pectin may be used to design drugs
      for the complex treatment in patients with chronic renal failure.

PMID- 20146408
TI  - [Surgical and interventional treatment of atrial fibrillation].
AB  - Results of surgical and interventional treatment of atrial fibrillation with the
      use of different methods are discussed. Original data are presented. Relative
      efficiency of radiofrequency, microwave, and cryogenic ablation is considered.

PMID- 20146409
TI  - [Histobiological features of posterior cranial fossa meningiomas and their impact
      on follow-up].
AB  - Total removal of posterior cranial fossa meningiomas often leads to complications
      due to localization, direction and nature of tumor growth. Radical excision as
      well as histological grade are the principal factors determining recurrence of
      disease in follow-up period. The paper evaluates the role of ki67 in progression
      of posterior cranial fossa meningiomas. We performed 189 immunohistochemical
      studies and katamnestic analysis of patients operated in Burdenko Neurosurgical
      Institute (Moscow). We showed that level of expression of ki67 correlates with
      histological grade of posterior fossa meningiomas. We established that recurrence
      free survival depends on ki67. This allows prediction of prognosis. Low
      expression of ki67 corresponds longer recurrence-free survival. If ki67
      expression is over 4% recurrence within 2 years after surgery is observed
      significantly more frequently. Multifactor statistical analysis confirmed
      prognostic value of ki67 especially in females and patients below 50 because
      terms of recurrences in these populations are significantly smaller. Obtained
      data prove versatility of ki67 in neurooncology which should enable its wider
      application in neurosurgical clinics.

PMID- 20146410
TI  - [Aneurysms of cerebral arteries in children and adolescents].
AB  - BACKGROUND: Intracranial aneurysms are rare lesions in children and adolescents
      and their epidemiology, clinical and anatomic features are poorly understood. Aim
      of the study was to reveal the specific features of cerebral aneurysms in
      children and adolescents and to develop guidelines for management of these
      patients. MATERIALS AND METHODS: The study was performed on consecutive series of
      125 patients under 18 years of age harboring 145 aneurysms. All of them were
      treated in Burdenko Neurosurgical Institute (Moscow, Russia) from 1987 to 2007.
      RESULTS: Specific features of pediatric aneurysms include: high incidence on a
      background of connective tissue disorder (42%) and abnormalities of circle of
      Willis (20%), frequent localization in bifurcation of internal carotid artery
      (13.8%), its cavernous segment (17.9%), or in posterior part of circle of Willis
      (23.5%). In children giant aneurysms were observed in 31.7% of cases, fusiform in
      19.3% and partially thrombosed in 33.8%. Complications of aneurysms in children
      with hemorrhagic type of course included recurrent hemorrhages (42.9%), hematomas
      (31%), hydrocephalus (16.7%) and seizures (33.3%). Generally, 107 pediatric
      patients (85.6%) with 118 aneurysm (81.4%) were operated. Microsurgical treatment
      was performed in 57% of patients and endovascular procedures in 43% In the series
      of 107 operated patients we observed excellent early postoperative results in 53
      cases (49.5%), good in 45 (42.1%) and poor in 9 (8.4%). Postoperative mortality
      was 0.95% (1 patient). CONCLUSION: Considerable proportion of complex aneurysms
      in children and adolescents produces certain difficulties of treatment; however,
      due to good functional outcomes in this age group the range of causes of denial
      must be minimized.

PMID- 20146411
TI  - [Trans-CSF electrostimulation of the brain in patients with posttraumatic
      vegetative state (theoretical basis and preliminary results)].
AB  - Theoretical basis of trans-CSF electrostimulation of the brainstem in
      posttraumatic vegetative state is described. Clinical and electrophysiological
      effects of the technique are presented.

PMID- 20146412
TI  - [Giant fusiform partially thrombosed aneurysm of fenestrated middle cerebral
      artery].
AB  - The authors describe a rare case of 15-year old patient with ruptured giant
      fusiform partially thrombosed aneurysm of fenestrated middle cerebral artery
      (MCA). The patient underwent surgical treatment: clipping of proximal and distal
      necks of aneurysm and thrombectomy. Intraoperative signs of MCA fenestration are
      described in details. The observation is instructive if a surgeon discovers
      'double-necked' aneurysm for selection of adequate tactics of aneurysm occlusion.

PMID- 20146413
TI  - [Principles of speciation of the plague causative agent Yersinia pestis:
      gradualism or saltation?].
AB  - The saltation origin of the causative agent of the plague Yersinia pestis from
      the pseudotuberculosis microbe Y. pseudotuberculosis O:1b has been proclaimed in
      recent investigations on molecular genetics. The speciation process in this case
      is proposed to be connected with horizontal inclusion of exogenous genetic
      structures (such as specific plasmids pFra and pPst) into the genome of the
      ancestral form. The alternative "Darwinian" model of the gradual origin of the
      plague agent is proposed based on ecological factors. The comparison of two
      evolutionary scenarios, saltation and gradual, is performed; the latter seems
      more likely.

PMID- 20146414
TI  - [How many neuroblasts build mushroom bodies in Lucilia caesar L. and Musca
      domestica L. (Diptera, Brachycera Cyclorrhapha)?].
AB  - The green-bottle fly Lucilia caesar and the housefly Musca domestica differ
      greatly in the number of neuroblasts producing mushroom bodies. Four neuroblasts
      were found in each mushroom body of Lucilia pupae, and its calyx has a quadruple
      structure. In the housefly, the number of mushroom body neuroblasts rises up 20
      in each brain hemisphere. This leads to a more complicated calyx structure. The
      neuroblast number observed in Lucilia and Musca is compared with that found in
      other Diptera.

PMID- 20146415
TI  - [Population genetics of 17 Y chromosome STR loci in a diverse ethnically groups
      of Polish citizens].
AB  - INTRODUCTION: The Y-chromosome has become a powerful tool in identification and
      characterization of male DNA in forensic analysis. If Y-STRs are used in forensic
      analysis it is important to establish a meaning of a match (how frequent a
      particular haplotype has been observed in a population). In literature higher
      haplotype frequency values were observed in samples from small and isolated
      populations such as Gypsies. Till now the lack is given on of the genetic
      differentiation Gypsies resident the territory of Poland and comparative research
      with a Polish population. This data are indispensable for the correct estimation
      of the power of the evidence in judicial expertise. MATERIAL AND METHODS: In this
      study, we reported basic forensic parameters for a 17 Y-STR from the set AmpFISTR
      Yfiler PCR Amplification Kit for the Gypsy population from the area of Poland and
      for the Polish population, and also the data were compared to other population
      samples from India and Europe. RESULTS: A total of 150 unrelated males from Gypsy
      population produced 78 different haplotypes of which 50 were unique. In
      population sample of 210 autochthonous Poles 195 different haplotypes were
      observed of which 185 were found in single individuals. The overall haplotype
      lower in Gypsy population but the haplotype sharing within population was higher.
      Both population groups can be distinguished based on AMOVA estimates. Thus a
      database of multi-locus haplotypes included various ethnic populations from
      Poland territory is required to provide a statistical estimate of the
      significance of a match.

PMID- 20146416
TI  - [Typeability of AmpFlSTR SGM Plus loci in kidney specimens incubated in different
      environments].
AB  - In consecutive stages of postmortem decomposition human hard tissues e.g. bones
      and teeth have been the most suitable material for genetic identification,
      however, its processing and DNA extraction is relatively costly and time
      consuming. The aim of the study was the assessment of the environmental effect on
      typeability of AmpFlSTR SGM Plus loci in the kidney. The specimens were collected
      during autopsies of five persons aged 20-30 years with post mortem interval (PMI)
      limited to 14 hours, and subsequently incubated at 21 degrees C and 4 degrees C
      in different environmental conditions. DNA was extracted by the organic method
      from tissue samples collected in 7-day intervals and subsequently typed using
      AmpFlSTR SGM Plus kit and ABI 310. The fastest decline of SGM Plus profiles was
      noted in specimens incubated at 21 degrees C in closed containers. The specimens
      incubated at 4 degrees C in closed containers were the most stable for SGM Plus
      typing. The differences in typeability rates for specimens incubated at 21degrees
      C in open vs. closed containers can be attributed to desiccation of the outermost
      layers of the former specimens.

PMID- 20146417
TI  - [Comparative analysis of traffic accident fatalities in autopsy material of 1970
      1986 and 1987-2006 collected at the Departament of Forensic Medicine Medical
      University of Bialystok].
AB  - INTRODUCTION, MATERIAL AND METHODS: The objective of the paper was a comparative
      analysis of traffic accident fatalities in autopsy material collected in the
      years 1970-1986 and 1987-2006 at the Department of Forensic Medicine, Medical
      University of Bialystok (624 and 1463 cases, respectively). Based on autopsy
      reports, main criteria included gender, site of death (urban area, rural area,
      non-built-up), mode of movement (driver, passenger, pedestrian, biker and
      cyclist), age, localisation of fatal injuries (head, thorax, abdomen and pelvis,
      upper and lower limbs, multiorgan injuries) and blood alcohol level. The
      collected data were analysed statistically according to the criteria applied and
      presented as text and graphs. RESULTS AND CONCLUSIONS: The number of traffic
      accidents increased by 4% in the years 1987-2006 when compared to period of 1970
      1986. The percentage male mortality increased 72-77%. Pedestrians predominated as
      traffic accident fatalities in Podlasie, with mortality rate slowly decreasing 47
      42%. In the years 1987-2006 mortality rate among drivers and bikers/motorbikes
      increased by 7% and decreased by 3%, respectively. Number of fatalities among
      passengers remained on constant level. Regardless of time period fatal cases were
      predominant in non-built-up area. Localisation of fatal injuries in respective
      groups appears invariable excluding pedestrian cases, where multiorgan rather,
      than head and neck injuries prevail. Mean age of traffic accident fatalities
      decreased by 3 years in the period of 1987-2006, predominantly due to the
      increasing number of fatal cases among young males. Mean blood alcohol level of
      traffic accident victims in the years 1987-2006 increased by 0.5 promille and 0.2
      promille in males and in females, respectively.

PMID- 20146418
TI  - [Types and incidence of intravital reactions in cases of suicidal hanging].
AB  - In the years 1980-2000 a total of 302 cases of suicidal hanging were analysed at
      the Department of Forensic Medicine, Medical University of Bialystok. In 140
      cases (46.36%) the knot was situated on the neck. In 131 corpses 206 intravital
      reactions were revealed. Descending incidence of the reactions was as follows:
      petechial subcutaneous facial and palpebre hemorrhages (33.5%), hemorrhages of
      muscules sternocleidomustoideus (18.4%), hemorrhages within ligature furrow
      (11.6%), vertebral cervical fracture (0.7%). In overall material 71.8% were sober
      persons presenting intravital reactions of the cervical organs to ligature.
      During autopsy examination skin sections were excised from ligature furrow,
      muscules sternocleidomustoideus and the carotid artery and then stained with
      hematoxilin-eosin, orcein, Fuller staining and alcian blue. The carotid artery
      sections were examined in scanning electron microscope. Macroscopically revealed
      intravital reactions were fully confirmable by scanning electron microscopic
      examination. Furthermore, in cases with negative macroscopic image lesions of the
      common carotid arteries were detected.

PMID- 20146419
TI  - Conversion of spent solid phosphoric Acid catalyst to environmentally friendly
      fertilizer.
AB  - Solid phosphoric acid (SPA) catalysts are widely used in the petroleum industry.
      Despite a high phosphorus content the spent catalyst is generally not reused.
      Moreover, due to the limited life spans that are achieved industrially, large
      quantities of spent catalyst requires disposal, often by landfill. SPA can be
      readily converted to fertilizer, but the presence of carbonaceous deposits on the
      catalyst presents a potential environmental hazard. This work demonstrates that
      these deposits are mostly polyaromatic (amorphous carbon) with smaller amounts of
      oxygenates and aliphatics. Neither the chemical makeup nor the physical structure
      of the catalyst or the presence of coke precludes it from use as fertilizer.
      Subsequently, the spent catalyst was milled, neutralized with lime and ammonium
      hydroxide, and then calcined to yield a phosphate-rich fertilizer. Toxicity
      characteristic leaching tests of the spent catalyst fertilizer showed low levels
      of metals and organics, establishing that no harmful compounds are likely to be
      absorbed into plant life or groundwater. A plant growth study of the spent
      catalyst fertilizer indicated that it is approximately as effective as
      superphosphate fertilizer when used in alkaline soil. The spent catalyst
      fertilizer is environmentally benign and economically efficient.

PMID- 20146420
TI  - Single-crystal membrane for anisotropic and efficient gas permeation.
AB  - Development of gas separation materials has been one of the basic requirements of
      industry. Microporous materials have adequate pores for gas separation and have
      contributed to the advancement of gas purification techniques. Because the
      simplest and most economical method would be membrane separation, various
      microporous membranes have been prepared and explored for their separation
      properties. However, a key issue remains as to how to generate defect-free
      membranes with practical gas permeance. Here we report the preparation of a well
      oriented single-crystal membrane with high permeance by using a flexible single
      crystal of [Cu(2)(bza)(4)(pyz)](n) possessing one-dimensional (1D) penetration
      channels; this membrane exhibits anisotropic gas permeation through the 1D
      channels with high permselectivity for H(2) and CO(2). Although the diameter of
      the neck of the narrow channels is smaller than the kinetic diameters of the
      sample gases, various gases pass through the 1D channels. This report provides a
      new way of developing gas permeation membranes as sophisticated crystal devices
      for gas purification techniques.

PMID- 20146421
TI  - Lignin extraction from straw by ionic liquids and enzymatic hydrolysis of the
      cellulosic residues.
AB  - Lignocellulose is a promising starting material for bioproducts, ranging from
      biofuels to specialty chemicals; however, lignocellulose is resistant to
      enzymatic degradation. Overcoming this resistance is therefore an important
      priority for the development of the lignocellulosic biorefinery concept. In this
      work, 1-ethyl-3-methylimidazolium acetate ([emim]Ac) was selected from six ionic
      liquid candidates for the extraction of lignin from triticale and wheat straw and
      flax shives. Lignin extractability, composition, and cellulose enzymatic
      digestibility of the residues after extraction by [emim]Ac were determined at
      various temperatures (70-150 degrees C) and time intervals (0.5-24 h). The
      optimal result (52.7% of acid insoluble lignin in triticale straw) was obtained
      at 150 degrees C after 90 min, yielding >95% cellulose digestibility of the
      residue. Little cellulose was extracted, and the extracted lignin was recovered
      by acid precipitation. Selective extraction of lignin by ionic liquids is a
      potentially efficient technique for the comprehensive utilization of
      lignocellulose.

PMID- 20146422
TI  - Characterization and comparative analysis of wheat high molecular weight glutenin
      subunits by SDS-PAGE, RP-HPLC, HPCE, and MALDI-TOF-MS.
AB  - High molecular weight glutenin subunits (HMW-GS) from 60 germplasms including 30
      common wheat cultivars and 30 related species were separated and characterized by
      a suite of separation methods including sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), reversed-phase high-performance liquid chromatography
      (RP-HPLC), high-performance capillary electrophoresis (HPCE), and matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
      Comparative analysis demonstrated that each methodology has its own advantages
      and disadvantages. The main drawback of SDS-PAGE was its overestimation of
      molecular mass and incorrect identification of HMW-GS due to its low resolution.
      However, it had the advantages of technical simplicity and low requirements of
      equipment; thus, it is suitable for large-scale and high-throughput HMW-GS
      screening for breeding programs, especially when the glutenin composition is
      clear in the breeding material. MALDI-TOF-MS clearly expressed many technical
      advantages among the four methods evaluated, including high throughput, high
      resolution, and accuracy; it was, however, associated with high equipment cost,
      thus preventing many breeding companies from accessing the technology. RP-HPLC
      and HPCE were found to be intermediate between SDS-PAGE and MALDI-TOF-MS. Both RP
      HPLC and HPCE demonstrated higher resolution and reproducibility over SDS-PAGE
      but lower detection power than MALDI-TOF-MS. Results demonstrated that MALDI-TOF
      MS is suitable for analyzing HMW-GS for routine breeding line screening and for
      identifying new genotypes.

PMID- 20146423
TI  - Physicochemical and emulsifying properties of whey protein isolate (WPI)-dextran
      conjugates produced in aqueous solution.
AB  - The physicochemical and emulsifying properties of protein and polysaccharide
      conjugates prepared under mild conditions were investigated. The covalently
      linked conjugates of whey protein isolate (WPI) and dextran (DX, 440 kDa) were
      produced by incubating aqueous solutions containing 10% WPI and 30% DX at pH 6.5
      and 60 degrees C for 48 h. After purification by anion-exchange chromatography
      and affinity chromatography, the conjugate had a weight-average molecular weight
      (M(w)) of 531 kDa and a radius of gyration (R(g)) of 30 nm as determined by size
      exclusion chromatography-multiangle laser light scattering (SEC-MALLS); the molar
      binding ratio of WPI to DX was calculated to be approximately 1:1. The purified
      conjugate had significantly improved heat stability when subjected to 80 degrees
      C for 30 min and remained soluble over a range of pH from 3.2 to 7.5 and ionic
      strengths from 0.05 to 0.2 M in contrast to native WPI. The emulsifying ability
      and emulsion stability made with WPI-DX conjugate were also improved compared to
      WPI and gum arabic (an emulsifier containing naturally derived glycoproteins).

PMID- 20146425
TI  - On the importance of the interplaquette spin exchanges in Na3RuO4: density
      functional theory analysis of the spin exchange and magnetic properties.
AB  - Na(3)RuO(4) contains layers of high-spin Ru(5+) d(3) ions grouped into isolated
      four-membered plaquettes. To determine the spin-lattice appropriate for
      Na(3)RuO(4), we evaluated the intraplaquette exchanges J(1), J(2), and J(3) as
      well as the interplaquette exchanges J(4) and J(5) by performing mapping analysis
      based on first-principles density functional theory calculations. In addition, we
      examined how the trends in the calculated J(1)-J(5) are related to the
      distortions of the RuO(6) octahedra in the four-membered plaquettes. The spin
      lattice of Na(3)RuO(4) is described by the intraplaquette exchanges J(1) and J(2)
      plus the interplaquette exchanges J(4) and J(5), with spin frustration arising
      from the (J(1), J(2), J(1)) and (J(5), J(4), J(5)) triangles. The trends in the
      calculated J(1)-J(5) reflect the distortions of the RuO(6) octahedra in the four
      membered plaquettes.

PMID- 20146426
TI  - Structural, magnetic, EPR, and electrochemical characterizations of a spin
      frustrated trinuclear Cr(III) polyoxometalate and study of its reactivity with
      lanthanum cations.
AB  - The asymmetric Cr(III) polyoxometalate complex Cs(10)[(gamma
      SiW(10)O(36))(2)(Cr(OH)(H(2)O))(3)] x 17 H(2)O (1) has been synthesized in water
      under atmospheric pressure from the trinuclear precursor
      [Cr(3)(CH(3)COO)(7)(OH)(2)] and the divacant ligand [gamma-SiW(10)O(36)](8-).
      Complex 1 is built up of two [gamma-SiW(10)O(36)](8-) Keggin units sandwiching a
      trinuclear {(Cr(III)(OH)(H(2)O))(3)} fragment where the paramagnetic centers are
      bridged by three mu-OH ligands forming a nearly isosceles triangle. The magnetic
      properties of this spin-frustrated system have thus been interpreted considering
      a 2-J Hamiltonian showing that the Cr(III) ions are antiferromagnetically coupled
      and that 1 possesses an S = 3/2 ground state with an S = 1/2 first excited state
      located at 11 cm(-1). These results have been confirmed by EPR spectroscopy
      measurements (Q-band), which have also enabled the quantification of the
      electronic parameters characterizing the quadruplet spin ground state. The
      magnitude of the magnetic exchange interactions and the nature of the ground
      state are discussed in light of previously reported isosceles triangular S = 3/2
      clusters. UV-visible and electrochemical studies have shown that 1 is stable in
      aqueous media in a 1-7 pH range. This stability is chemically confirmed by the
      study of the reactivity of 1 with La(III) cations, which has allowed the
      isolation of the Cs(4)[(gamma
      SiW(10)O(36))(2)(Cr(OH)(H(2)O))(3)(La(H(2)O)(7))(2)] x 20 H(2)O compound (2).
      Indeed, during the synthetic process of this 3d-4f system, the integrity of the
      [(gamma-SiW(10)O(36))(2)(Cr(OH)(H(2)O))(3)](10-) building unit constituting 1 is
      maintained despite the high oxophilic character of the La(III) ions. The single
      crystal X-ray diffraction study of 2 has revealed that in the solid state the
      rare earth cations connect these subunits, affording a 3d-4f double-chain
      monodimensional system.

PMID- 20146427
TI  - Hybrid scorpionate/cyclopentadienyl magnesium and zinc complexes: synthesis,
      coordination chemistry, and ring-opening polymerization studies on cyclic esters.
AB  - The reaction of the hybrid scorpionate/cyclopentadienyl lithium salt
      [Li(bpzcp)(THF)] [bpzcp = 2,2-bis(3,5-dimethylpyrazol-1-yl)-1,1
      diphenylethylcyclopentadienyl] with 1 equiv of RMgCl proceeds cleanly to give
      very high yields of the corresponding monoalkyl kappa(2)-NN-eta(5)-C(5)H(4)
      magnesium complexes [Mg(R)(kappa(2)-eta(5)-bpzcp)] (R = Me 1, Et 2, (n)Bu 3,
      (t)Bu 4, CH(2)SiMe(3) 5, CH(2)Ph 6). Hydrolysis of the hybrid lithium salt
      [Li(bpzcp)(THF)] with NH(4)Cl/H(2)O in ether cleanly affords the two previously
      described regioisomers: (bpzcpH) 1-[2,2-bis(3,5-dimethylpyrazol-1-yl)-1,1
      diphenylethyl]-1,3-cyclopentadiene (a) and 2-[2,2-bis(3,5-dimethylpyrazol-1-yl)
      1,1-diphenylethyl]-1,3-cyclopentadiene (b). Subsequent reaction of the bpzcpH
      hybrid ligand with ZnR(2) quantitatively yields the monoalkyl kappa(2)-NN
      eta(1)(pi)-C(5)H(4) zinc complexes [Zn(R){kappa(2)-eta(1)(pi)-bpzcp}] (R = Me 7,
      Et 8, (t)Bu 9, CH(2)SiMe(3) 10). Additionally, magnesium alkyls 1, 2, 4, and 5
      can act as excellent cyclopentadienyl and alkyl transfers to the zinc metal
      center and yield zinc alkyls 7-10 in good yields. The single-crystal X-ray
      structures of the derivatives 4, 5, 7, and 10 confirm a 4-coordinative structure
      with the metal center in a distorted tetrahedral geometry. Interestingly, whereas
      alkyl magnesium derivatives 4 and 5 present a eta(5) coordination mode for the
      cyclopentadienyl fragment, zinc derivatives 7 and 10 feature a peripheral
      eta(1)(pi) arrangement in the solid state. Furthermore, the reaction of the
      hybrid lithium salt [Li(bpzcp)(THF)] with 1 equiv of ZnCl(2) in tetrahydrofuran
      (THF) affords very high yields of the chloride complex [ZnCl{kappa(2)-eta(1)(pi)
      bpzcp}] (11). Compound 11 was used as a convenient starting material for the
      synthesis of the aromatic amide zinc compound [Zn(NH-4-MeC(6)H(4)){kappa(2)
      eta(1)(pi)-bpzcp}] (12), by reaction with the corresponding aromatic primary
      amide lithium salt. Alternatively, aliphatic amide and alkoxide derivatives were
      only accessible by protonolysis of the bis(amide) complexes [M{N(SiMe(3))(2)}(2)]
      (M = Mg, Zn) and the mixed ligand complex [EtZnOAr)] with the hybrid ligand
      bpzcpH to afford [Zn(R){kappa(2)-eta(1)(pi)-bpzcp}] (R = N(SiMe(3))(2) 13, R =
      2,4,6-Me(3)C(6)H(2)O 14) and [Mg{N(SiMe(3))(2)}(kappa(2)-eta(5)-bpzcp)] (15).
      Finally, alkyl and alkoxide-containing complexes 1-10 and 14 can act as highly
      effective single-component living initiators for the ring-opening polymerization
      of epsilon-caprolactone and lactides over a wide range of temperatures. Epsilon
      caprolactone is polymerized within minutes to give high molecular weight polymers
      with medium-broad polydispersities (M(n) > 10(5), M(w)/M(n) = 1.45). Lactide
      afforded poly(lactide) materials with medium molecular weights and
      polydispersities as narrow as M(w)/M(n) = 1.02. Additionally, polymerization of L
      lactide occurred without racemization in the propagation process and offered
      highly crystalline, isotactic poly(L-lactides) with very high melting
      temperatures (T(m) = 165 degrees C). Microstructural analysis of poly(rac
      lactide) by (1)H NMR spectroscopy revealed that propagations occur without
      appreciable levels of stereoselectivity. Polymer end group analysis showed that
      the polymerization process is initiated by alkyl transfer to the monomer.

PMID- 20146428
TI  - Atmospheric pressure scanning transmission electron microscopy.
AB  - Scanning transmission electron microscope (STEM) images of gold nanoparticles at
      atmospheric pressure have been recorded through a 0.36 mm thick mixture of CO,
      O2, and He. This was accomplished using a reaction cell consisting of two
      electron-transparent silicon nitride membranes. Gold nanoparticles of a full
      width at half-maximum diameter of 1.0 nm were visible above the background noise,
      and the achieved edge resolution was 0.4 nm in accordance with calculations of
      the beam broadening.

PMID- 20146429
TI  - A path to ultranarrow patterns using self-assembled lithography.
AB  - The templated self-assembly of block copolymer (BCP) thin films can generate
      regular arrays of 10-50 nm scale features with good positional and orientational
      accuracy, but the ordering, registration and pattern transfer of sub-10-nm
      feature sizes is not well established. Here, we report solvent-annealing and
      templating methods that enable the formation of highly ordered grating patterns
      with a line width of 8 nm and period 17 nm from a self-assembled poly(styrene-b
      dimethylsiloxane) (PS-PDMS) diblock copolymer. The BCP patterns can be registered
      hierarchically on a larger-period BCP pattern, which can potentially diversify
      the available pattern geometries and enables precise pattern registration at
      small feature sizes. Sub-10-nm-wide tungsten nanowires with excellent order and
      uniformity were fabricated from the self-assembled patterns using a reactive ion
      etching process.

PMID- 20146430
TI  - Mild and general method for the alpha-arylation of heteroaromatic ketones.
AB  - The development of a general and mild method for Pd-catalyzed alpha-arylation of
      a variety of ketones bearing multiple heteroatoms is described. The ligand to
      metal ratio and the position of the heteroatoms with respect to the carbonyl
      moiety significantly impact the efficiency of these transformations. In addition,
      these conditions were successfully applied to the alpha-arylation of cyclic
      imines. A detailed investigation of the scope of this methodology, including the
      effect of the ligand to metal ratio, is discussed.

PMID- 20146431
TI  - Fast separation and determination of sterols in vegetable oils by
      ultraperformance liquid chromatography with atmospheric pressure chemical
      ionization mass spectrometry detection.
AB  - A method for the determination of sterols in vegetable oils by ultraperformance
      liquid chromatography (UPLC) with atmospheric pressure chemical ionization mass
      spectrometry detection has been developed. The separation of sterols was
      optimized in terms of mobile phase composition, column temperature and flow rate.
      The optimal conditions were achieved using an Acquity UPLC BEH C18 column (50 x
      2.1 mm, 1.7 microm) with a mobile phase consistent of acetonitrile/water (0.01%
      acetic acid) using a linear gradient, at a flow rate of 0.8 mL min(-1) and column
      temperature of 10 degrees C, giving a total analysis time below 5 min. The
      determination was performed in selective ion recording mode. The limits of
      detection were in all cases below 0.07 microg mL(-1), with relative standard
      deviation values of retention times and peak areas below 0.4 and 5%,
      respectively. The content of main sterols present in several vegetable oils with
      different botanical origins was also established.

PMID- 20146432
TI  - Stability of aqueous films between bubbles. Part 2. Effects of trace impurities
      and evaporation.
AB  - The stability of water films has been investigated with a Mysels-Scheludko type
      film balance. Minor trace impurities in water do not affect the lifetime of water
      films under vapor saturation, but significantly influence the stability in free
      evaporation. Trace amounts of positively adsorbed contaminants induce Marangoni
      driven flow that destabilizes films under evaporation conditions whereas
      negatively adsorbed electrolytes actually prolong stability by reversing
      interfacial tension gradients and driving a steady circulation within the film.
      At high thinning rates, pure-water films develop exotic-appearing flow patterns
      and break due to a strong coupling between hydrodynamic and interfacial tension
      gradient adsorption stresses. The most dominant factor of transient film
      stabilization in dynamic conditions under evaporation is a surface tension
      gradient created in the film. We discuss surface tension gradients in transient
      films created by temperature differences, impurity concentration, and expansion
      of the films.

PMID- 20146433
TI  - Sesquiterpenes from Maytenus jelskii as potential cancer chemopreventive agents.
AB  - Seven new (1-4 and 7-9) sesquiterpenes with a dihydro-beta-agarofuran skeleton,
      along with four known compounds (5, 6, 10, and 11), have been isolated from the
      leaves of Maytenus jelskii. The structures of the new compounds were elucidated
      by means of spectroscopic data analysis, including 1D and 2D NMR techniques, and
      their absolute configurations were determined by circular dichroism and chemical
      correlations. The compounds have been tested for their inhibitory effects on
      Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O
      tetradecanoylphorbol-13-acetate (TPA). Compound 10 was found to be an effective
      antitumor-promoting agent and also showed a potent chemopreventive effect in an
      in vivo two-stage carcinogenesis model.

PMID- 20146434
TI  - Stability of aqueous films between bubbles. Part 1. The effect of speed on bubble
      coalescence in purified water and simple electrolyte solutions.
AB  - Film thinning experiments have been conducted with aqueous films between two air
      phases in a thin film pressure balance. The films are free of added surfactant
      but simple NaCl electrolyte is added in some experiments. Initially the
      experiments begin with a comparatively large volume of water in a cylindrical
      capillary tube a few millimeters in diameter, and by withdrawing water from the
      center of the tube the two bounding menisci are drawn together at a prescribed
      rate. This models two air bubbles approaching at a controlled speed. In pure
      water, the results show three regimes of behavior depending on the approach
      speed; at slow speed (<1 microm/s) it is possible to form a flat film of pure
      water, approximately 100 nm thick, that is stabilized indefinitely by disjoining
      pressure due to repulsive double-layer interactions between naturally charged
      air/water interfaces. The data are consistent with a surface potential of -57 mV
      on the bubble surfaces. At intermediate approach speed (approximately 1-150
      microm/s), the films are transiently stable due to hydrodynamic drainage effects,
      and bubble coalescence is delayed by approximately 10-100 s. At approach speeds
      greater than approximately 150 microm/s, the hydrodynamic resistance appears to
      become negligible, and the bubbles coalesce without any measurable delay.
      Explanations for these observations are presented that take into account
      Derjaguin-Landau-Verwey-Overbeek and Marangoni effects entering through
      disjoining pressure, surface mobility, and hydrodynamic flow regimes in thin film
      drainage. In particular, it is argued that the dramatic reduction in hydrodynamic
      resistance is a transition from viscosity-controlled drainage to inertia
      controlled drainage associated with a change from immobile to mobile air/water
      interfaces on increasing the speed of approach of two bubbles. A simple model is
      developed that accounts for the boundaries between different film stability or
      coalescence regimes. Predictions of the model are consistent with the data, and
      the effects of adding electrolyte can be explained. In particular, addition of
      electrolyte at high concentration inhibits the near-instantaneous coalescence
      phenomenon, thereby contributing to increased foam film stability at high
      approach speeds, as reported in previous literature. This work highlights the
      significance of bubble approach speed as well as electrolyte concentration in
      affecting bubble coalescence.

PMID- 20146435
TI  - Design, synthesis, and evaluation of 2-methyl- and 2-amino-N-aryl-4,5
      dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4
      (thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors.
AB  - Following the recent discovery and development of 2-anilino-4-(thiazol-5
      yl)pyrimidine cyclin dependent kinase (CDK) inhibitors, a program was initiated
      to evaluate related ring-constrained analogues, specifically, 2-methyl- and 2
      amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines for inhibition of
      CDKs. Here we report the rational design, synthesis, structure-activity
      relationships (SARs), and cellular mode-of-action profile of these second
      generation CDK inhibitors. Many of the analogues from this chemical series
      inhibit CDKs with very low nanomolar K(i) values. The most potent compound
      reported in this study inhibits CDK2 with an IC(50) of 0.7 nM ([ATP] = 100
      microM). Furthermore, an X-ray crystal structure of 2-methyl-N-(3-(nitro)phenyl)
      4,5-dihydrothiazolo[4,5-h]quinazolin-8-amine (11g), a representative from the
      chemical series in complex with cyclin A-CDK2, is reported, confirming the design
      rationale and expected binding mode within the CDK2 ATP binding pocket.

PMID- 20146437
TI  - Fabrication of high-quality In2Se3 nanowire arrays toward high-performance
      visible-light photodetectors.
AB  - The synthesis of high-quality In2Se3 nanowire arrays via thermal evaporation
      method and the photoconductive characteristics of In2Se3 individual nanowires are
      first investigated. The electrical characterization of a single In2Se3 nanowire
      verifies an intrinsic n-type semiconductor behavior. These single-crystalline
      In2Se3 nanowires are then assembled in visible-light sensors which demonstrate a
      fast, reversible, and stable response. The high photosensitivity and quick
      photoresponse are attributed to the superior single-crystal quality and large
      surface-to-volume ratio resulting in fewer recombination barriers in
      nanostructures. These excellent performances clearly demonstrate the possibility
      of using In2Se3 nanowires in next-generation sensors and detectors for
      commercial, military, and space applications.

PMID- 20146438
TI  - Atomic-scale geometry and electronic structure of catalytically important pd/au
      alloys.
AB  - Pd/Au bimetallic alloys catalyze many important reactions ranging from the
      synthesis of vinyl acetate and hydrogen peroxide to the oxidation of carbon
      monoxide and trimerization of acetylene. It is known that the atomic-scale
      geometry of these alloys can dramatically affect both their reactivity and
      selectivity. However, there is a distinct lack of experimental characterization
      and quantification of ligand and ensemble effects in this system. Low
      temperature, ultrahigh vacuum scanning tunneling microscopy is used to
      investigate the atomic-scale geometry of Pd/Au111 near-surface alloys and to
      spectroscopically probe their local electronic structure. The results reveal that
      the herringbone reconstruction of Au111 provides entry sites for the
      incorporation of Pd atoms in the Au surface and that the degree of mixing is
      dictated by the surface temperature. At catalytically relevant temperatures the
      distribution of low coverages of Pd in the alloy is random, except for a lack of
      nearest neighbor pairs in both the surface and subsurface sites. Scanning
      tunneling spectroscopy is used to examine the electronic structure of the
      individual Pd atoms in surface and subsurface sites. This work reveals that in
      both surface and subsurface locations, Pd atoms display a very similar electronic
      structure to the surrounding Au atoms. However, individual surface and subsurface
      Pd atoms are depleted of charge in a very narrow region at the band edge of the
      Au surface state. dI/dV images of the phenomena demonstrate the spatial extent of
      this electronic perturbation.

PMID- 20146436
TI  - CO binding and ligand discrimination in human myeloperoxidase.
AB  - Despite the fact that ferrous myeloperoxidase (MPO) can bind both O(2) and NO,
      its ability to bind CO has been questioned. UV/visible spectroscopy was used to
      confirm that CO induces small spectral shifts in ferrous MPO, and Fourier
      transform infrared difference spectroscopy showed definitively that these arose
      from formation of a heme ferrous-CO compound. Recombination rates after CO
      photolysis were monitored at 618 and 645 nm as a function of CO concentration and
      pH. At pH 6.3, k(on) and k(off) were 0.14 mM(-1) x s(-1) and 0.23 s(-1),
      respectively, yielding an unusually high K(D) of 1.6 mM. This affinity of MPO for
      CO is 10 times weaker than its affinity for O(2). The observed rate constant for
      CO binding increased with increasing pH and was governed by a single protonatable
      group with a pK(a) of 7.8. Fourier transform infrared spectroscopy revealed two
      different conformations of bound CO with frequencies at 1927 and 1942 cm(-1).
      Their recombination rate constants were identical, indicative of two forms of
      bound CO that are in rapid thermal equilibrium rather than two distinct protein
      populations with different binding sites. The ratio of bound states was pH
      dependent (pK(a) approximately 7.4) with the 1927 cm(-1) form favored at high pH.
      Structural factors that account for the ligand-binding properties of MPO are
      identified by comparisons with published data on a range of other ligand-binding
      heme proteins, and support is given to the recent suggestion that the proximal
      His336 in MPO is in a true imidazolate state.

PMID- 20146439
TI  - Electronic anabolic steroid recognition with carbon nanotube field-effect
      transistors.
AB  - A proof of concept of the electronic detection of two anabolic steroids,
      stanozolol (Stz) and methylboldenone (MB), was carried out using two specific
      antibodies and arrays of carbon nanotube field-effect transistors (CNTFETs).
      Antibodies specific for Stz and MB were prepared and immobilized on the carbon
      nanotubes (CNTs) using two different approaches: direct noncovalent bonding of
      antibodies to the devices and bonding the antibodies covalently to a polymer
      previously attached to the CNTFETs. The results indicated that CNTFETs bonded to
      specific antibodies covalently or noncovalently are able to detect the presence
      of steroids. Statistically significant changes in the threshold voltage and drain
      current were registered in the transistors, allowing the steroids to be
      recognized. On the other hand, it was determined that the specific antibodies do
      not detect other steroids other than Stz and MB, such as nandrolone (ND) because,
      in this case, statistically significant changes in the transistors were not
      detected. The polymer prevents the aggregation of antibodies on the electrodes
      and decreases the transistor hysteresis. Nevertheless, it is not able to avoid
      the nonspecific adsorption of streptavidin, meaning that nonspecific adsorption
      on CNTs remains a problem and that this methodology is only useful for purified
      samples. Regarding the detection mechanism, in addition to charge transfer,
      Schottky barrier, SB, modification, and scattering potential reported by other
      authors, an electron/hole trapping mechanism leading to hysteresis modification
      has been determined. The presence of polymer seems to hinder the modulation of
      the electrode-CNT contact.

PMID- 20146440
TI  - N-demethylation of N,N-dimethylanilines by the benzotriazole N-oxyl radical:
      evidence for a two-step electron transfer-proton transfer mechanism.
AB  - The reaction of the benzotriazole N-oxyl radical (BTNO) with a series of 4-X-N,N
      dimethylanilines (X = CN, CF(3), CO(2)CH(2)CH(3), CH(3), OC(6)H(5), OCH(3)) has
      been investigated in CH(3)CN. Product analysis shows that the radical, 4-X
      C(6)H(4)N(CH(3))CH(2)(*), is first formed, which can lead to the N-demethylated
      product or the product of coupling with BTNO. Reaction rates were found to
      increase significantly by increasing the electron-donating power of the aryl
      substituents (rho(+) = -3.8). With electron-donating substituents (X = CH(3),
      OC(6)H(5), OCH(3)), no intermolecular deuterium kinetic isotope effect (DKIE) and
      a substantial intramolecular DKIE are observed. With electron-withdrawing
      substituents (X = CN, CF(3), CO(2)CH(2)CH(3)), substantial values of both
      intermolecular and intramolecular DKIEs are observed. These results can be
      interpreted on the basis of an electron-transfer mechanism from the N,N
      dimethylanilines to the BTNO radical followed by deprotonation of the anilinium
      radical cation (ET-PT mechanism). By applying the Marcus equation to the kinetic
      data for X = CH(3), OC(6)H(5), OCH(3) (rate-determining ET), a reorganization
      energy for the ET reaction was determined (lambda(BTNO/DMA) = 32.1 kcal mol(-1)).
      From the self-exchange reorganization energy for the BTNO/BTNO(-) couple, a self
      exchange reorganization energy value of 31.9 kcal mol(-1) was calculated for the
      DMA(*+)/DMA couple.

PMID- 20146441
TI  - Temperature and pH dependence of enzyme-catalyzed hydrolysis of trans
      methylstyrene oxide. A unifying kinetic model for observed hysteresis,
      cooperativity, and regioselectivity.
AB  - The underlying enzyme kinetics behind the regioselective promiscuity shown by
      epoxide hydrolases toward certain epoxides has been studied. The effects of
      temperature and pH on regioselectivity were investigated by analyzing the
      stereochemistry of hydrolysis products of (1R,2R)-trans-2-methylstyrene oxide
      between 14-46 degrees C and pH 6.0-9.0, either catalyzed by the potato epoxide
      hydrolase StEH1 or in the absence of enzyme. In the enzyme-catalyzed reaction, a
      switch of preferred epoxide carbon that is subjected to nucleophilic attack is
      observed at pH values above 8. The enzyme also displays cooperativity in
      substrate saturation plots when assayed at temperatures < or = 30 degrees C and
      at intermediate pH. The cooperativity is lost at higher assay temperatures.
      Cooperativity can originate from a kinetic mechanism involving hysteresis and
      will be dependent on the relationship between k(cat) and the rate of
      interconversion between two different Michaelis complexes. In the case of the
      studied reactions, the proposed different Michaelis complexes are enzyme
      substrate complexes in which the epoxide substrate is bound in different binding
      modes, allowing for separate pathways toward product formation. The assumption of
      separated, but interacting, reaction pathways is supported by that formation of
      the two product enantiomers also displays distinct pH dependencies of
      k(cat)/K(M). The thermodynamic parameters describing the differences in
      activation enthalpy and entropy suggest that (1) regioselectivity is primarily
      dictated by differences in activation entropy with positive values of both
      DeltaDeltaH(++) and DeltaDeltaS(++) and (2) the hysteretic behavior is linked to
      an interconversion between Michaelis complexes with rates increasing with
      temperature. From the collected data, we propose that hysteresis,
      regioselectivity, and, when applicable, hysteretic cooperativity are closely
      linked properties, explained by the kinetic mechanism earlier introduced by our
      group.

PMID- 20146442
TI  - Structure of nanoscale truncated octahedral DNA cages: variation of single
      stranded linker regions and influence on assembly yields.
AB  - The assembly, structure, and stability of DNA nanocages with the shape of
      truncated octahedra have been studied. The cages are composed of 12 double
      stranded B-DNA helices interrupted by single-stranded linkers of thymidines of
      varying length that constitute the truncated corners of the structure. The
      structures assemble with a high efficiency in a one-step procedure, compared to
      previously published structures of similar complexity. The structures of the
      cages were determined by small-angle X-ray scattering. With increasing linker
      length, there is a systematic increase of the cage size and decrease of the twist
      angle of the double helices with respect to the symmetry planes of the cage
      structure. In the present study, we demonstrate the length of the single-stranded
      linker regions, which impose a certain degree of flexibility to the structure, to
      be the important determinant for efficient assembly. The linker length can be
      decreased to three thymidines without affecting assembly yield or the overall
      structural characteristics of the DNA cages. A linker length of two thymidines
      represents a sharp cutoff abolishing cage assembly. This is supported by energy
      minimization calculations suggesting substantial hydrogen bond deformation in a
      cage with linkers of two thymidines.

PMID- 20146443
TI  - Hydrogen isotope separation in carbon nanotubes: calculation of coupled
      rotational and translational States at high densities.
AB  - The effect of the quantized rotational degrees of freedom of hydrogen on the
      adsorption and sieving properties in carbon nanotubes is studied using computer
      simulations. We have developed a highly efficient multiple timestep algorithm for
      hybrid Monte Carlo sampling of quantized rotor configurations and extended the
      grand canonical Boltzmann bias method to rigid linear molecules. These new
      computational tools allow us to calculate accurately the quantum sieving
      selectivities for cases of extreme two-dimensional confinement as a function of
      pressure. The para-T2/para-H2 selectivity at 20 K is analyzed as a function of
      the tube diameter and the density of adsorbed hydrogen. Extraordinarily high
      selectivities, up to 2.6 x 10(8), are observed in the narrowest nanotube. The
      quantized nature of the rotational degrees of freedom is found to dramatically
      affect adsorption and selectivity for hydrogen isotopes adsorbed in very narrow
      nanotubes. The T2/H2 zero-pressure selectivity increases from 2.4 x 10(4) to 1.7
      x 10(8) in the (3,6) nanotube at 20 K when quantum rotations are accounted for.
      The isotopic selectivity is found to increase with pressure, tending to a
      constant value at saturation. A simplified mean-field model is used to discuss
      the origin of this behavior.

PMID- 20146444
TI  - Thermodynamics of charged nanoparticle adsorption on charge-neutral membranes: a
      simulation study.
AB  - The interactions between charged nanoparticles (NPs) and charge-neutral
      phospholipid membranes are investigated by coarse-grained molecular dynamics
      simulations. Three kinds of nanoparticles are modeled with different surface
      charge densities: the uncharged one, the positively charged one, and the
      negatively charged one. We find that the electrostatic attraction improves the
      adhesion of a charged nanoparticle to the membrane. With the increase of
      electrostatic energy, a charged NP can be almost fully wrapped by the membrane.
      In addition, analyses of structural variations suggest that the adhesion of a
      charged NP induces a local transition in fluid bilayers. Some thermodynamic
      quantities such as free energy, entropy, and enthalpy are also obtained to
      explain the process of NPs binding. Furthermore, the bending energy of wrapping
      of NPs against the electrostatic potential energy is also discussed based on the
      Helfrich theory, indicating that the driving force of the wrap originates from
      the gain in electrostatic energy at the cost of the elastic energy of
      biomembranes. Our observations shed light on the origin of experiments of the
      wrap as well as the mechanism of structural transitions of membranes due to the
      electrostatic binding.

PMID- 20146445
TI  - Transport of semivolatile organic compounds to the Tibetan plateau: spatial and
      temporal variation in air concentrations in mountainous Western Sichuan, China.
AB  - The distribution of organochlorine pesticides and polychlorinated biphenyls in
      air along an altitudinal transect on Balang Mountain in western China was
      measured by deploying XAD-2 resin based passive air samplers in duplicate at
      seven sites with elevations ranging from 1242 to 4485 m above sea level for five
      consecutive six-month periods between 2005 and 2008. Analyzed by gas
      chromatography-high resolution mass spectrometry, concentrations of
      hexachlorobenzene were highest, followed by hexachlorocyclohexanes, DDT-related
      compounds and PCB congeners 28 and 52. Except for hexachlorobenzene, which had
      largely uniform concentrations in space and time, there were clear seasonal
      variations with concentrations in summer being higher than in winter. With a few
      exceptions, concentrations that vary little with altitude suggest that the
      presence of these chemicals in the area is almost entirely due to atmospheric
      transport, most likely from the Chengdu plain. This is supported by similarities
      in the relative abundance of different compounds and in the differences between
      summer and winter concentrations measured in the city of Chengdu and in the
      mountains. Furthermore, air mass trajectories during the sampling period often
      originate to the East, passing over the Western part of the Sichuan basin,
      including the Chengdu plain, prior to arriving at the sampling sites. Higher
      summer time values in the mountains are due to more contaminated air being blown
      into the region, presumably due either to higher pesticide usage in summer or due
      to higher temperatures leading to higher evaporation in source regions. Air and
      soil from the region are in equilibrium with respect to alpha-HCH, gamma-HCH, and
      HCB, whereas a situation of net deposition prevails for p,p'-DDE and p,p'-DDT.

PMID- 20146446
TI  - Stationary-phase optimized selectivity liquid chromatography: development of a
      linear gradient prediction algorithm.
AB  - Stationary-phase optimized selectivity liquid chromatography (SOS-LC) is a tool
      in reversed-phase LC (RP-LC) to optimize the selectivity for a given separation
      by combining stationary phases in a multisegment column. The presently
      (commercially) available SOS-LC optimization procedure and algorithm are only
      applicable to isocratic analyses. Step gradient SOS-LC has been developed, but
      this is still not very elegant for the analysis of complex mixtures composed of
      components covering a broad hydrophobicity range. A linear gradient prediction
      algorithm has been developed allowing one to apply SOS-LC as a generic RP-LC
      optimization method. The algorithm allows operation in isocratic, stepwise, and
      linear gradient run modes. The features of SOS-LC in the linear gradient mode are
      demonstrated by means of a mixture of 13 steroids, whereby baseline separation is
      predicted and experimentally demonstrated.

PMID- 20146447
TI  - Structural characterization of phospholipids and peptides directly from tissue
      sections by MALDI traveling-wave ion mobility-mass spectrometry.
AB  - Ion mobility-mass spectrometry (IM-MS) provides rapid two-dimensional separations
      based on analyte apparent surface area or collision cross section (CCS, A(2)) and
      mass-to-charge, respectively. Recently, traveling-wave (t-wave) IM-MS was
      developed which uses electrodynamic rather than electrostatic fields commonly
      used in drift cell IM-MS instruments. The underlying theory for obtaining CCS
      data is well developed for drift cell IM-MS, while strategies for obtaining CCS
      values from t-wave IM-MS data remains an active area of research. In this report,
      methods were developed and validated to obtain CCS values of phospholipids and
      peptides directly from thin tissue sections by MALDI t-wave IM-MS using CCS
      calibrants measured by MALDI drift cell IM-MS. Importantly, the average percent
      difference between t-wave and drift cell CCS measurements is minimized by
      calibrating with the same biomolecular class. Calibrating t-wave phospholipid CCS
      values with drift cell peptide CCS measurements results in an average percent
      difference of ca. 7% between the same lipids measured using t-wave and drift cell
      IM-MS, while this improves to <0.5% when drift cell phospholipid CCS values are
      used for calibrating t-wave data. A suite of CCS values are reported for lipids
      and peptides that were determined directly from tissue, i.e. without the need for
      tissue extraction and further purification steps.

PMID- 20146448
TI  - Pt-Ag catalysts as cathode material for oxygen-depolarized electrodes in
      hydrochloric acid electrolysis.
AB  - Pt-Ag nanoparticles were prepared on a glassy carbon (GC) surface by pulsed
      electrodeposition and tested using cyclic voltammetry and scanning
      electrochemical microscopy (SECM) with respect to their possible use as catalyst
      material for oxygen reduction in 400 mM HCl solution. For comparison, a Pt
      catalyst was investigated under similar conditions. The redox competition mode of
      scanning electrochemical microscopy (RC-SECM) was adapted to the specific
      conditions caused by the presence of Cl(-) ions and used to visualize the local
      catalytic activity of the Pt-Ag deposits. Similarly prepared Pt deposits were
      shown to dissolve underneath the SECM tip. Pt-Ag composites showed improved long
      term stability toward oxygen reduction as compared with Pt even under multiple
      switching off to open-circuit potential in 400 mM HCl.

PMID- 20146450
TI  - Challenges in environmental analytical chemistry.

PMID- 20146449
TI  - High-resolution desorption electrospray ionization mass spectrometry for chemical
      characterization of organic aerosols.
AB  - Characterization of the chemical composition and chemical transformations of
      secondary organic aerosol (SOA) is both a major challenge and the area of
      greatest uncertainty in current aerosol research. This study presents the first
      application of desorption electrospray ionization combined with high-resolution
      mass spectrometry (DESI-MS) for detailed chemical characterization and studies of
      chemical aging of organic aerosol (OA) samples collected on Teflon substrates.
      DESI-MS offers unique advantages both for detailed characterization of chemically
      labile components in OA that cannot be detected using traditional electrospray
      ionization mass spectrometry (ESI-MS) and for studying chemical aging of OA. DESI
      MS enables rapid characterization of OA samples collected on substrates by
      eliminating the sample preparation stage. In addition, it enables detection and
      structural characterization of chemically labile molecules in OA samples by
      minimizing the residence time of analyte in the solvent. In this study, DESI-MS
      and tandem mass spectrometry experiments (MS/MS) were used to examine chemical
      aging of SOA produced by the ozonolysis of limonene (LSOA) in the presence of
      gaseous ammonia. Exposure of LSOA to ammonia resulted in measurable changes in
      the optical properties of the sample observed using ultraviolet (UV)-visible
      spectroscopy. High-resolution DESI-MS analysis demonstrated that chemical aging
      results in formation of highly conjugated nitrogen-containing species that are
      most likely responsible for light-absorbing properties of the aged LSOA. Detailed
      analysis of the experimental data allowed us to identify several key aging
      reactions, including the transformation of carbonyls to imines, intramolecular
      dimerization of imines with other carbonyl compounds in SOA, and intermolecular
      cyclization of imines. This study presents an important step toward understanding
      the formation of light-absorbing OA (brown carbon) in the atmosphere.

PMID- 20146451
TI  - Preparation of the 2'-deoxynucleosides of 2,6-diaminopurine and isoguanine by
      direct glycosylation.
AB  - The purine nucleoside 2,6-diaminopurine-2'-deoxyriboside is prepared by the
      direct glycosylation of the 2,6-bis(tetramethylsuccinimide) derivative of the
      parent purine heterocycle 4 with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-erythro
      pentofuranosyl chloride 5 using the sodium salt method. 2'-Deoxyisoguanosine is
      prepared from 2,6-diaminopurine by a five-step procedure. The purine heterocycle
      isoguanine is prepared by selective diazotization of 2,6-diaminopurine and then
      converted to the N9-trityl derivative to increase solubility. After silylation of
      the O(2)-carbonyl with TMSCl, the N(6)-amino group is protected as the
      tetramethylsuccinimide (M(4)SI). The O(2)-carbonyl is protected as the DPC
      derivative, and the trityl group is removed. The resulting product is
      glycosylated in good yield to generate fully protected 2'-deoxyisoguanosine.

PMID- 20146452
TI  - Strain-tunable chemiresistor.
AB  - We have developed a resistance-based chemical sensor (chemiresistor) for volatile
      organic compounds whose sensitivity can be reversibly increased over a range of
      nearly 2 decades by the application of tensile strain. This polymer-based sensor
      is comprised of Au-plated magnetic particles structured into conducting chains by
      the application of a magnetic field during the curing of the prepolymer resin.
      The resistance of this field-structured composite increases when an analyte vapor
      swells the polymer and reduces the contact pressure between particles. We have
      found that applying a tensile strain increases both the sensor resistance and
      sensitivity, as defined by its relative resistance change. This increase in
      sensitivity is a smooth, continuous function of the applied strain, and the
      effect is fully reversible. Sensitivity tuning enables the response curve of the
      sensor to be dynamically optimized for sensing analytes over a wide concentration
      range.

PMID- 20146453
TI  - Carbon microelectrodes with a renewable surface.
AB  - Electrode fouling decreases sensitivity and can be a substantial limitation in
      electrochemical experiments. In this work we describe an electrochemical
      procedure that constantly renews the surface of a carbon microelectrode using
      periodic triangle voltage excursions to an extended anodic potential at a scan
      rate of 400 V s(-1). This methodology allows for the regeneration of an
      electrochemically active surface and restores electrode sensitivity degraded by
      irreversible adsorption of chemical species. We show that repeated voltammetric
      sweeps to moderate potentials in aqueous solution causes oxidative etching of
      carbon thereby constantly renewing the electrochemically active surface.
      Oxidative etching was established by tracking surface-localized fluorine atoms
      with XPS, by monitoring changes in carbon surface morphology with AFM on
      pyrolyzed photoresist films, and also by optical and electron microscopy. The use
      of waveforms with extended anodic potentials showed substantial increases in
      sensitivity toward the detection of catechols. This enhancement arose from the
      adsorption of the catechol moiety that could be maintained with a constant
      regeneration of the electrode surface. We also demonstrate that application of
      the extended waveform could restore the sensitivity of carbon microelectrodes
      diminished by irreversible adsorption (electrode fouling) of byproducts resulting
      from the electrooxidation and polymerization of tyramine. Overall, this work
      brings new insight into the factors that affect electrochemical processes at
      carbon electrodes and provides a simple method to remove or reduce fouling
      problems associated with many electrochemical experiments.

PMID- 20146454
TI  - Immobilization of recombinant vault nanoparticles on solid substrates.
AB  - Native vaults are nanoscale particles found abundantly in the cytoplasm of most
      eukaryotic cells. They have a capsule-like structure with a thin shell
      surrounding a "hollow" interior compartment. Recombinant vault particles were
      found to self-assemble following expression of the major vault protein (MVP) in a
      baculovirus expression system, and these particles are virtually identical to
      native vaults. Such particles have been recently studied as potential delivery
      vehicles. In this study, we focus on immobilization of vault particles on a solid
      substrate, such as glass, as a first step to study their interactions with cells.
      To this end, we first engineered the recombinant vaults by fusing two different
      tags to the C-terminus of MVP, a 3 amino acid RGD peptide and a 12 amino acid RGD
      strep-tag peptide. We have demonstrated two strategies for immobilizing vaults on
      solid substrates. The barrel-and-cap structure of vault particles was observed
      for the first time, by atomic force microscopy (AFM), in a dry condition. This
      work proved the feasibility of immobilizing vault nanoparticles on a material
      surface, and the possibility of using vault nanoparticles as localized and
      sustainable drug carriers as well as a biocompatible surface moiety.

PMID- 20146456
TI  - Binding of Europium(III) to a non-nucleosidic phenanthroline linker in DNA.
AB  - Eu(III) complexes of DNA containing a non-nucleosidic linker, a derivative of
      1,10-phenanthroline-2,6-dicarboxamide (Q), are studied with the goal of forming
      novel lanthanide ion binding sites that are incorporated in the backbone of DNA.
      One oligonucleotide is short and unstructured (TTTQTTT (QT6)) and the other (5'
      AGCTCGGTCAQCGAGAGTGCA-3' (SQ)) is studied both in single-stranded form and in the
      presence of a partially complementary DNA strand. Luminescence spectroscopy
      studies show that Eu(III) binds to SQ, QT6, AQB, or QB 1100-, 56-, 23-, or 27
      fold more tightly, respectively, than to a simple 1,10-phenanthroline-2,6
      dicarboxamide ligand (Q1). Direct excitation and phenanthroline sensitized
      luminescence spectroscopy supports binding of Eu(III) to the phenanthroline
      linker in QT6 and in double-stranded DNA formed from SQ and partially
      complementary sequences that place Q in a bulge-like position. Eu(III) hydration
      numbers range from 3 to 5 when bound to the phenanthroline moiety in modified
      DNA, consistent with binding to the tetradentate linker and, in some cases,
      coordination to other groups in the DNA. Thermal melting experiments show that Q
      in a bulge-like structure stabilizes double-stranded DNA and that Eu(III) binding
      does not markedly affect the stability of the duplex. 

PMID- 20146455
TI  - Excellent performance in lithium-ion battery anodes: rational synthesis of
      Co(CO3)0.5(OH)0.11H2O nanobelt array and its conversion into mesoporous and
      single-crystal Co3O4.
AB  - Herein, we report a rational method to synthesize a Co3O4 nanobelt array on a
      conducting substrate and functionalize it in the application of Li-ion battery
      anodes, which is a novel and facile approach to access the nanobelt array of
      transition metal oxides. Compared to the previous reports, the as-prepared
      samples in our experiments exhibited both mesoporosity and single-crystallinity,
      and meanwhile, good contact with the conducting substrate (via a thin layer of
      TiO2) provided an express pathway for charge transfer when they were applied in
      Li-ion batteries without any need to add other ancillary materials (carbon black
      or binder) to enhance the system's conductivity and stability. Under the
      condition of high charge-discharge current density of 177 mA/g in Li-ion
      batteries' testing, the Co3O4 nanobelt array was capable of retaining the
      specific capacity of 770 mAh/g over 25 cycles. Moreover, even though the charge
      discharge rates were increased to 1670 and 3350 mA/g, it still could have reached
      the stable retention of the specific capacity of 510 and 330 mAh/g beyond 30
      cycles, respectively, indicating an obtainable excellent rate capability. More
      importantly, the improved performance in Li-ion battery testing was definitely
      ascribed to the unique structures in our samples after elaborate analysis. So the
      final conclusion would be given that the lab-synthesized Co3O4 nanobelt array
      potentially could be a highly qualified candidate for Li-ion battery anodes in
      some practical fields, where high capacity and good capability are strictly
      required.

PMID- 20146457
TI  - Single crystals of Rb4C60: synthesis and structure determination.
AB  - Single crystals of Rb(4)C(60) were obtained at 973 K in a closed niobium ampule,
      and the structure was determined by X-ray diffraction (I4/mmm, Z = 2, a = b =
      11.9783(17) A, c = 11.035(2) A, and V = 1583.3(4) A(3)). The refinement was
      successful without any bond distance restraint and resulted in average C-C bond
      lengths of d(6:6) = 1.383(5) A and d(5:6) = 1.453(5) A. C(60)(4-) is rotationally
      disordered and has the shape of a distorted truncated icosahedron (D(2h)). Using
      the new structural data, density functional theory calculations obtain a metallic
      ground state.

PMID- 20146458
TI  - Theoretical mechanistic study on the ion-molecule reaction of CHCl- with CS2.
AB  - A detailed theoretical study for the poorly understood ion-molecule reaction of
      CHCl(-) with CS(2) is explored at the B3LYP/6-311++G(d,p) and CCSD(T)/6
      311++G(3df,2p) (single-point) levels. Various possible reaction pathways are
      considered. On the doublet potential energy surface, five dissociation products
      are both thermodynamically and kinetically possible. Among these products, P(7)
      (SCHCl(-) + CS) may be the most favorable product with predominant abundances,
      whereas P(1) (Cl(-) + SCHCS) and P(2) (Cl(-) + HCCSS) may be the second and third
      feasible products followed by the almost negligible P(3) (Cl(-) + HSCCS), P(4)
      (CClS(-) + HCS), and P(6) (S-cCCS(-) + HCl). Because the isomers and transition
      states involved in the most feasible pathways all lie below the reactant, the
      title reaction is expected to be fast, which is consistent with the measured
      large rate constant in recent experiment. The present paper may provide a useful
      guide for understanding other analogous ion-molecule reactions such as CHF(-) and
      CHBr(-) with CS(2), COS, and CO(2).

PMID- 20146459
TI  - Au111-based nanotemplates by gd alloying.
AB  - A new class of nanostructured templates is obtained by submitting Au111 films to
      high-temperature vapor deposition of Gd in ultrahigh vacuum. In a low coverage
      regime, Gd atoms are embedded in the topmost Au layer, inducing a structural
      transformation of the herringbone reconstruction to create a network of trigons.
      At higher dose, the reactive deposition of Gd leads to the formation of an
      atomically perfect GdAu2 surface compound characterized by a long-range periodic
      Moire pattern. Both the trigon and Moire lattices are highly ordered
      nanostructures, which turned out to be robust templates to grow metal nanodots.
      As a test example, Co was deposited at room temperature, forming uniform dots
      that faithfully arrange by following the underlying trigons or Moire periodicity.
      For the latter, one can achieve nanodot arrays that exhibit record areal density.

PMID- 20146460
TI  - Integration of protein processing steps on a droplet microfluidics platform for
      MALDI-MS analysis.
AB  - A droplet-based (digital) microfluidics platform has been developed to prepare
      and purify protein samples for measurement by matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS). Liquid droplets are moved in
      air by sequentially applying an electric potential to an array of electrodes
      patterned beneath a hydrophobic dielectric layer. We show that a complete
      integrated sequence of protein processing steps can be performed on this
      platform, including disulfide reduction, alkylation, and enzymatic digestion,
      followed by cocrystallization with a MALDI matrix and analysis of the sample in
      situ by MALDI-MS. Proteins carbonic anhydrase, cytochrome c, and ubiquitin were
      used to demonstrate the digestion and postdigestion steps; insulin, serum
      albumin, and lysozyme were used to illustrate the complete sequence of protein
      processing steps available with the platform. Several functional improvements in
      the platform are reported, notably, the incorporation of acetonitrile in the
      protein droplets to facilitate movement, and patterning the device surfaces to
      optimize sample crystallization. The method is fast, simple, repeatable, and
      results in lower reagent consumption and sample loss than conventional techniques
      for proteomics sample preparation.

PMID- 20146461
TI  - Application of the stabilization method to temporary anion states of pi-ligand
      transition-metal carbonyls in density functional theory.
AB  - In this paper, density functional theory is used to investigate (benzene)chromium
      tricarbonyl, (cyclopentadienyl)manganese tricarbonyl, (1,3-butadiene)iron
      tricarbonyl, and (cyclopentadienyl)cobalt dicarbonyl. For the energies of low
      lying temporary anion states, the stabilized Koopmans-based (S-KB) and stabilized
      Koopmans theorem (S-KT) methods are adopted. Stabilization is accomplished by
      varying the exponents of appropriate diffuse functions. Results indicate that the
      calculations of S-KB using PBEPBE and S-KT using CAM-B3LYP are able to yield
      energies of temporary anion states in good agreement with the experimental
      values. Furthermore, the ionization potentials can be determined accurately via
      the Koopmans-based (KB) PBEPBE method.

PMID- 20146462
TI  - XAFS investigation of the interactions of U(VI) with secondary mineralization
      products from the bioreduction of Fe(III) oxides.
AB  - Biogenic Fe(II) phases (magnetite, green rust, siderite, vivianite, etc.) provide
      a reservoir of reducing capacity in many subsurface environments that may
      contribute to the reduction of contaminants such as U(VI). We have examined the
      uptake and reduction of U(VI) in the presence of biogenic green rust (BioGR),
      magnetite (BioMAG), and siderite (BioSID) formed during the reduction of Fe(III)
      oxides by Shewanella putrefaciens CN32. Within 48 h, total solution-phase U(VI)
      concentrations decreased from 500 microM to 1.5 microM, 392 microM, and 472
      microM in the U-BioGR, U-BioMAG, and U-BioSID systems, respectively. Analysis of
      the samples by U L(III) extended X-ray absorption fine structure spectroscopy
      (EXAFS) indicated that despite a stoichiometric excess of Fe(II), no more than 6%
      of U(VI) was reduced to U(IV) in the U-BioSID system, and no more than 22% of
      U(VI) was reduced in the U-BioMAG system. For comparison, in the U-BioGR system,
      >99% of U(VI) was reduced to U(IV). Uptake of U(VI) by BioGR and BioMAG was
      accompanied by formation of nanoparticulate uraninite. The U EXAFS data for the U
      BioSID system were consistent with partial U(VI)/U(IV) substitution for Fe(II) in
      the surface layer of siderite particles and adsorption of U(IV).

PMID- 20146463
TI  - Levels and potential sources of decabromodiphenyl ethane (DBDPE) and
      decabromodiphenyl ether (DecaBDE) in lake and marine sediments in Sweden.
AB  - Decabromodiphenyl ethane (DBDPE) is a brominated flame retardant (BFR) used as a
      replacement for the structurally similar decabromodiphenyl ether (decaBDE), which
      is a regulated environmental contaminant of concern. DBDPE has been found in
      indoor dust, sewage sludge, sediment, and biota, but little is known about its
      occurrence and distribution in the environment In this paper, sediment was
      analyzed from 11 isolated Swedish lakes and along a transect running from central
      Stockholm through the Stockholm archipelago to the Baltic Sea. DBDPE was present
      in all samples. In lake sediment, the levels ranged from 0.23 to 11 ng/g d.wt.
      and were very similar to the levels of decaBDE (0.48-11 ng/g d.wt.). Since the
      lakes have no known point sources of BFRs, their presence in the sediments
      provides evidence for long-range atmospheric transport and deposition. In the
      marine sediment, the DBDPE and decaBDE levels decreased by a factor of 20-50 over
      40 km from the inner harbor to the outer archipelago. There the DBDPE and decaBDE
      levels were similar to the levels in nearby isolated lakes. The results indicate
      that contamination of the Swedish environment with DBDPE has already approached
      that of decaBDE, and that this contamination is primarily occurring via the
      atmosphere.

PMID- 20146464
TI  - Phosphorus speciation in agro-industrial byproducts: sequential fractionation,
      solution (31)P NMR, and P K- and L(2,3)-edge XANES spectroscopy.
AB  - Little is known about P species in agro-industrial byproducts from developing
      countries, which may be either pollutants or valuable soil amendments. The
      present study speciated P in dry (COD) and wet (COW) coffee, sisal (SIS), barley
      malt (BEB) and sugar cane processing (FIC) byproducts, and filter cakes of
      linseed (LIC) and niger seed (NIC)with sequential fractionation, solution (31)P
      nuclear magnetic resonance (NMR) spectroscopy, and P K- and L(2,3)-edge X-ray
      absorption near-edge structure (XANES) spectroscopy. The sequential P
      fractionation recovered 59% to almost 100% of total P (P(t)), and more than 50%
      of P(t) was extracted by H(2)O and NaHCO(3) in five out of seven samples.
      Similarly, the NaOH + EDTA extraction for solution (31)P NMR recovered 48-94% of
      P(t). The (31)P NMR spectra revealed orthophosphate (6-81%), pyrophosphate (0
      10%), and orthophosphate monoesters (6-94%). Orthophosphate predominated in COD,
      COW, SIS, and FIC, whereas BEB, UC, and NIC were rich in orthophosphate
      monoesters. The concentrations of P(i), and P(o) determined in the sequential and
      NaOH + EDTA extractions and (31)P NMR spectra were strongly and positively
      correlated (r = 0.88-1.00). Furthermore, the P K- and L(2,3)-edge XANES confirmed
      the H(2)SO(4)--P(i) detected in the sequential fractionation by unequivocal
      identification of Ca--P phases in a few samples. The results indicate that the
      combined use of all four analytical methods is crucial for comprehensive P
      speciation in environmental samples and the application of these byproducts to
      soil.

PMID- 20146466
TI  - Magnetic behavior of odd- and even-electron metal carbonyl clusters: the case
      study of [Co(8)Pt(4)C(2)(CO)(24)](n-) (n = 1, 2) carbide cluster.
AB  - The reaction of [Co(6)C(CO)(15)](2-) with 2 equiv of PtCl(2)(Et(2)S)(2) affords
      the new heterobimetallic [Co(8)Pt(4)C(2)(CO)(24)](2-), [1](2-), carbonyl cluster.
      [1](2-) undergoes reversible chemical and electrochemical oxidation and reduction
      processes disclosing a complete series of [1](n-) (n = 1-4) clusters. The mono-
      and dianion of [1](n-) have been isolated as their tetra-substituted ammonium
      salts and fully characterized by means of IR, (13)C NMR, ESI-MS, and X-ray
      crystallography. Variable-temperature (VT) solid-state EPR studies on pure
      crystalline samples indicate that both [1](2-) and [1](-*) are paramagnetic, due
      to a doublet state of the latter and a triplet state of [1](2-). This conclusion
      is supported by SQUID measurements on the same crystalline sample of [1](2-). The
      present study indisputably demonstrates that even-electron transition metal
      carbonyl clusters (TMCC) can be magnetic.

PMID- 20146467
TI  - Controlled self-assembly of monodisperse niosomes by microfluidic hydrodynamic
      focusing.
AB  - Niosomes are synthetic membrane vesicles formed by self-assembly of nonionic
      surfactant, often in a mixture with cholesterol and dicetyl phosphate. Because of
      their inner aqueous core and bilayer membrane shell, niosomes are commonly used
      as carriers of treatment agents for pharmaceutical and cosmetic applications or
      contrast agents for clinical imaging applications. In those applications,
      niosomes are considered as a more economical and stable alternative to their
      biological counterpart (i.e., liposomes). However, conventional bulk method of
      niosome preparation requires bulk mixing of two liquid phases, which is time
      consuming and not well-controlled. Such mixing conditions often lead to large
      niosomes with high polydispersity in size and thus affect the consistency of
      niosome dosage or imaging quality. In this study, we present a new method of
      niosome self-assembly by microfluidic hydrodynamic focusing to improve on the
      size and size distributions of niosomes. By taking advantage of the rapid and
      controlled mixing of two miscible fluids (i.e., alcohol and water) in
      microchannels, we were able to obtain in seconds nanoscaled niosomes with
      approximately 40% narrower size distributions compared to the bulk method. We
      further investigated different parameters that might affect on-chip assembly of
      niosomes, such as (1) conditions for the microfluidic mixing, (2) chemical
      structures of the surfactant used (i.e., sorbitan esters Span 20, Span 60, and
      Span 80), and (3) device materials for the microchannel fabrication. This work
      suggests that microfluidics may facilitate the development and optimization of
      biomimetic colloidal systems for nanomedicine applications.

PMID- 20146468
TI  - Dependence of catalytic activity on driving force in solution assays and protein
      film voltammetry: insights from the comparison of nitrate reductase mutants.
AB  - Rhodobacter sphaeroides periplasmic nitrate reductase (Rs NapAB) is one of the
      enzymes whose assays give odd results: in spectrophotometric assays with methyl
      viologen as the electron donor, the activity increases as the reaction
      progresses, whereas the driving force provided by the soluble redox partner
      decreases; in protein film voltammetry (PFV), whereby the enzyme directly
      exchanges electrons with an electrode, the activity of NapAB decreases at large
      overpotential, whereas a monotonic increase is expected [Elliott, S. J., et al.
      (2002) Biochim. Biophys. Acta 1555, 54-59]. The relations between these phenomena
      and the catalytic mechanism are still debated. By studying NapAB mutants, we
      found that the peculiar dependences of electrochemical and solution activities on
      driving force are greatly affected by substituting certain amino acids that are
      located in the vicinity of the active site (M153, Q384, R392); this led us to
      establish and discuss the relation between the experimental parameters of the
      electrochemical and spectrophotometric assays: we show that the rate of reduction
      of the enzyme (which depends on the electrode potential or on the concentration
      of reduced MV) modulates the activity of the enzyme, but the "solution potential"
      does not. Our results also support the view that the complex profiles of activity
      versus potential are fingerprints of the active site chemistry, rather than
      direct consequences of changes in the redox states of relays that are remote from
      the active site.

PMID- 20146469
TI  - How solvent modulates hydroxyl radical reactivity in hydrogen atom abstractions.
AB  - The hydroxyl radical (HO*) is a highly reactive oxygen-centered radical whose
      bimolecular rate constants for reaction with organic compounds (hydrogen atom
      abstraction) approach the diffusion-controlled limit in aqueous solution. The
      results reported herein show that hydroxyl radical is considerably less reactive
      in dipolar, aprotic solvents such as acetonitrile. This diminished reactivity is
      explained on the basis of a polarized transition state for hydrogen abstraction,
      in which the oxygen of the hydroxyl radical becomes highly negative and can serve
      as a hydrogen bond acceptor. Because acetonitrile cannot participate as a
      hydrogen bond donor, the transition state cannot be stabilized by hydrogen
      bonding, and the reaction rate is lower; the opposite is true when water is the
      solvent. This hypothesis explains hydroxyl radical reactivity both in solution
      and in the gas phase and may be the basis for a "containment strategy" used by
      Nature when hydroxyl radical is produced endogenously.

PMID- 20146470
TI  - Scanning calorimetric detections of multiple DNA biomarkers contained in complex
      fluids.
AB  - Most of the existing techniques cannot be used to detect molecular biomarkers
      contained in complex fluids due to issues such as enzyme inhibition or signal
      interference. We have developed a nanoparticle-based scanning calorimetric method
      for the highly sensitive detections of multiple DNA biomarkers contained in cell
      lysate and milk by using solid-liquid phase change nanoparticles as thermal
      barcodes. The detection is based on the principle that the temperature of solid
      will not rise above the melting temperature unless all solid is molten, thus
      nanoparticles have sharp melting peaks during the thermal scan process. A one-to
      one correspondence can thus be created between one type of nanoparticles and one
      type of biomarker, i.e., multiple biomarkers can be detected at the same time
      using a combination of nanoparticles. The melting temperature and the heat flow
      reflect the type and the concentration of the biomarker, respectively. The target
      oligonucleotides at low concentration in cell lysate (80 pM) have been detected
      through thermal signal transduction. The melting temperature of nanoparticles can
      be designed to avoid interference from coexisting species contained in the
      fluids, bringing simultaneously high sensitivity and multiplicity, as well as
      sample preparation benefits to biomarker detections.

PMID- 20146471
TI  - Study of ion-paired iridium complexes (soft salts) and their application in
      organic light emitting diodes.
AB  - Three Ir-based materials were synthesized through metathesis reaction between
      halide and alkali metal salts of two cationic and three anionic Ir complexes,
      respectively. The resulting "soft salt" complexes are composed of an
      organometallic cation and an organometallic anion. The electrochemical and
      photophysical characterization of these compounds is reported. The redox
      potentials of the soft salts are shown to be determined by the lowest energy
      potentials of the two ions. Energy transfer between the ions in solution is
      observed, and found to take place at diffusion controlled rates. Organic LEDs
      were prepared with each of the three soft salts, using the simple structure of
      anode/PVK/soft salt/BCP/cathode. The soft salts yielded maximal external quantum
      efficiencies (EQE) ranging from 0.2% to 4.7%. The study suggests that the
      internal energy alignment between two ions in the soft salts is responsible for
      the widely disparate results. To achieve a high EQE, it is critical to have the
      HOMO and LUMO values of one of the ions fall between those of the other ion, that
      is, one ion has both the lowest oxidation potential and the least negative
      reduction potential.

PMID- 20146472
TI  - Introducing capillary electrophoresis with laser-induced fluorescence (CE-LIF) as
      a potential analysis and quantification tool for galactooligosaccharides
      extracted from complex food matrices.
AB  - The analysis and quantification of (galacto)oligosaccharides from food matrices
      demands both a reproducible extraction method as well as a sensitive and accurate
      analytical method. Three typical matrices, namely, infant formula, fruit juice,
      and a maltodextrin-rich preparation, to which a commercial galactooligosaccharide
      mixture was added in a product concentration range from 1.25 to 30%, served as
      model substrates. Solid-phase extraction on graphitized carbon material upon
      enzymatic amyloglucosidase pretreatment enabled a good recovery and a selective
      purification of the different galactooligosaccharide structures from the
      exceeding amounts of particularly lactose and maltodextrins. With the
      implementation of capillary electrophoresis in combination with laser-induced
      fluorescence (CE-LIF) detection, a new possibility facilitating a sensitive
      qualitative and quantitative determination of the galactooligosaccharide contents
      in the different food matrices is outlined. Simultaneous monitoring and
      quantifying prebiotic oligosaccharides embedded in food matrices presents a
      promising and important step toward an efficient monitoring of individual
      oligosaccharides and is of interest for research areas dealing with small
      quantities of oligosaccharides embedded in complex matrices, e.g., body liquids.

PMID- 20146473
TI  - Room-temperature reaction of oxygen with gold: an in situ ambient-pressure X-ray
      photoelectron spectroscopy investigation.
AB  - The interaction of O(2) with gold foil and gold nanoparticles grown by thermal
      deposition on TiO(2)(110) was studied by in situ ambient pressure X-ray
      photoelectron spectroscopy at room temperature. No spontaneous dissociation of
      O(2) was observed either on Au foil or on Au nanoparticles up to 1 Torr of O(2).
      X-ray irradiation, however, is very effective in promoting gold oxidation on both
      surfaces in the presence of O(2). Our results help reconcile recent conflicting
      experimental observations regarding the activation of molecular oxygen, which is
      a crucial issue in Au catalyzed oxidation reactions.

PMID- 20146474
TI  - Using neural networks to estimate the losses of ascorbic acid, total phenols,
      flavonoid, and antioxidant activity in asparagus during thermal treatments.
AB  - Artificial neural networks (ANNs) with back-propagation algorithm were developed
      to predict the percentage loss of ascorbic acid, total phenols, flavonoid, and
      antioxidant activity in different segments of asparagus during water blanching at
      temperatures ranging from 65 to 95 degrees C as a function of blanching time and
      temperature. In this study, the one-hidden-layer ANNs are used, and the number of
      neurons in the hidden layer were chosen by trial and error. Optimized ANN models
      were developed for predicting nutrient losses in bud, upper, middle, and butt
      segments of asparagus. ANN models were then tested against an independent data
      set. Our results showed that the predicted values of the correlation coefficients
      between experimental and ANNs ranged from 0.8166 to 0.9868. Therefore, ANNs could
      be potential tools for the prediction of nutrient losses in vegetables during
      thermal treatments.

PMID- 20146475
TI  - Sorption-desorption behavior of atrazine on soils subjected to different organic
      long-term amendments.
AB  - Sorption of atrazine on soils subjected to three different organic amendments was
      measured using a batch equilibrium technique. A higher K(F) value (2.20 kg(-1)(mg
      L(-1))(-N)) was obtained for soil fertilized with compost, which had a higher
      organic matter (OM) content. A correlation between the K(FOC) values and the
      percentage of aromatic carbon in OM was observed. The highest K(FOC) value was
      obtained for the soil with the highest aromatic content. Higher aromatic content
      results in higher hydrophobicity of OM, and hydrophobic interactions play a key
      role in binding of atrazine. On the other hand, the soil amended with farmyard
      manure had a higher content of carboxylic units, which could be responsible for
      hydrogen bonding between atrazine and OM. Dominance of hydrogen bonds compared to
      hydrophobic interactions can be responsible for the lower desorption capacity
      observed with the farmyard manure soil. The stronger hydrogen bonding can reduce
      the leaching of atrazine into drinking water resources and runoff to rivers and
      other surface waters.

PMID- 20146476
TI  - Isoliquiritigenin entails blockade of TGF-beta1-SMAD signaling for retarding high
      glucose-induced mesangial matrix accumulation.
AB  - Diabetic nephropathy characterized as mesangial fibrosis and glomerulosclerosis
      results in renal failure and end-stage renal diseases. Enhanced expression and
      secretion of connective tissue growth factor (CTGF) play an important role in the
      expansion of glomerular mesangial matrix mostly composed of type IV collagen.
      Isoliquiritigenin can prevent various renal injuries via its anti-inflammatory
      action. However, the effect of isoliquiritigenin on diabetic nephropathy has
      never been explored. The present study was to investigate whether nontoxic
      isoliquiritigenin inhibited high glucose (HG)-induced mesangial fibrosis by
      retarding formation of type IV collagen as well as CTGF in human mesangial cells
      (HRMC). Serum starved cells were cultured in media containing 5.5 mM glucose plus
      27.5 mM mannitol as an osmotic control or 33 mM glucose for 3 days with and
      without 1-20 microM isoliquiritigenin. Exposure of cells to HG caused marked
      increases in collagen secretion and CTGF expression, which was dose-dependently
      reversed by isoliquiritigenin at the transcriptional levels. Additionally,
      isoliquiritigenin boosted HG-plummeted type matrix metalloproteinase-1 (MT-1 MMP)
      expression and dampened HG-elevated tissue inhibitor of MMP-2 (TIMP-2)
      expression, facilitating the degradation of mesangial matrix. Isoliquiritigenin
      inhibited HG-upregulated CTGF and TIMP-2 expression via disturbing TGF-beta1
      signaling in HRMC, as evidenced by TGF-beta receptor I kinase (TGF-beta RI)
      inhibitor. HG-activated SMAD2 through autocrine TGF-beta signaling was repealed
      by > or =10 microM isoliquiritigenin. HG induced SMAD4 expression of HRMC and
      obliterated antagonistic SMAD7, whereas isoliquiritigenin suppressed induction of
      TGF-beta RII and TGF-beta RI with blunting their downstream SMAD signaling. The
      results demonstrate that the bioactive isoliquiritigenin in licorice diminished
      mesangial matrix accumulation in response to ambient HG through retarding TGF
      beta1-SMAD signaling transduction. Therefore, isoliquiritigenin may be a
      potential therapeutic agent for the prevention and treatment of mesangial
      fibrosis and glomerulosclerosis leading to diabetic nephropathy due to
      longstanding diabetes mellitus.

PMID- 20146477
TI  - Electronic communication in dinuclear C(4)-bridged tungsten complexes.
AB  - The dinuclear tungsten carbyne [X(CO)(2)(dppe)WC(4)W(dppe)(CO)(2)X] (dppe = 1,2
      bis(diphenylphosphino)ethane; X = I (3), Cl (7)) complexes were prepared from the
      bisacetylide precursor Li(2)[(CO)(3)(dppe)WC(4)W(CO)(3)(dppe)] (2) via oxidative
      replacement of one CO group at each tungsten center with a halide substituent.
      The iodide ligand in 3 could be substituted with isothiocyanate or triflate
      resulting in [X(CO)(2)(dppe)WC(4)W(dppe)(CO)(2)X] complexes (X = NCS (8), OTf
      (9)). Substitution of two and all four CO ligands in 3 was achieved via
      subsequent photolytic or thermal activation with dppe. The "half-substituted"
      complex [I(CO)(2)(dppe)WC(4)W(dppe)(2)I] (11) allows reversible one-electron
      oxidation which results in the monocationic species
      [I(CO)(2)(dppe)WC(4)W(dppe)(2)I][PF(6)] (11[PF(6)]). The "all-dppe substituted"
      complex [I(dppe)(2)WC(4)W(dppe)(2)I] (10) possesses two reversible redox states
      leading to the stable monocationic [I(dppe)(2)WC(4)W(dppe)(2)I][PF(6)]
      (10[PF(6)]) and the dicationic [I(dppe)(2)WC(4)W(dppe)(2)I][PF(6)](2)
      (10[PF(6)](2)) compounds. The complexes 2, 3, [W(CO)(3)(dppe)(C[triple
      bond]CPh)(I)] (4), [X(CO)(2)(dppe)W[triple bond]C-C(Me)=C(Me)-C[triple
      bond]W(dppe)(CO)(2)X] (X = I (5), Cl (6)), 7, 8, 10, 11 and 11[PF(6)] were
      characterized by single crystal X-ray diffraction. The electronic properties of
      complexes 10, 10[PF(6)], 10[PF(6)](2), as well as of compounds 11 and 11[PF(6)],
      were investigated using cyclic voltammetry (CV), EPR, IR, near-IR spectroscopy,
      and magnetization measurements. These studies showed that the [W][triple bond]C
      C[triple bond]C-C[triple bond][W] canonical form of the bridged system with
      strong tungsten-carbon interaction contributes significantly to the electronic
      coupling in the mixed-valent species 10[PF(6)] (comproportionation constant K(c)
      = 7.5 x 10(4)) and to the strong antiferromagnetic coupling in the dicationic
      complex 10[PF(6)](2) (exchange integral J = -167 cm(-1)). In addition, the rate
      for electron transfer between the tungsten centers in 10[PF(6)] was evaluated by
      near-IR and IR studies.

PMID- 20146478
TI  - Investigation of the aroma-active compounds formed in the maillard reaction
      between glutathione and reducing sugars.
AB  - Aroma-active compounds formed during the thermal reaction between glutathione
      (GSH) and reducing sugars were analyzed by gas chromatography-mass spectrometry
      (GC-MS) and GC-olfactometry (GC-O) with aroma extract dilution analysis (AEDA).
      Application of AEDA to glutathione Maillard reaction products (GSH MRPs) led to
      the identification of 19 aroma-active compounds in the thermal reaction of
      glutathione with glucose or fructose. In addition, the carbohydrate module
      labeling (CAMOLA) approach was also employed to elucidate the formation pathways
      for selected target sulfur aroma compounds, such as 5-methylthiophene-2
      carbaldehyde and 3-methylthiophene-2-carbaldehyde, which have not been reported
      previously. The intact carbon skeleton of glucose via 3-deoxyhexosone is
      incorporated into 5-methylthiophene-2-carbaldehyde with the hydrogen sulfide of
      GSH. On the other hand, the formation of 3-methylthiophene-2-carbaldehyde may
      occur via the recombination of a C-4 sugar fragment and mercaptoacetaldehyde.

PMID- 20146479
TI  - Small molecule JNK (c-Jun N-terminal kinase) inhibitors.

PMID- 20146480
TI  - The amino-terminus of angiotensin II contacts several ectodomains of the
      angiotensin II receptor AT1.
AB  - G protein-coupled receptors (GPCRs) are the largest family of cell surface
      receptors and major targets for drug development. Herein, we sought to identify
      the regions of the human angiotensin II (AngII) type 1 (hAT(1)) receptor binding
      cleft that interact with all positions of the AngII using photoaffinity labeling.
      We conducted a complete iterative walk-through of the AngII sequence with either
      p-benzoyl-L-phenylalanine (Bpa) or p-[3-(trifluoromethyl)-3H-diazirin-3-yl]-L
      phenylalanine (Tdf) to yield two series of eight photoreactive analogues.
      Pharmacological properties assessment of these sixteen analogues showed that the
      CAM receptor has a structure-activity relationship (SAR) more amenable to the
      amino acid substitutions at positions 1, 2, 3, and 5 of AngII than the WT
      receptor. Photoaffinity labeling of the CAM receptor with the selected analogues,
      which exhibit different but complementary photochemical properties, suggested
      that the AngII amino-terminus resides in a hydrophilic environment and interacts
      simultaneously with different regions of the hAT(1) receptor, including several
      ectodomains.

PMID- 20146481
TI  - Toward biophysical probes for the 5-HT3 receptor: structure-activity relationship
      study of granisetron derivatives.
AB  - This report describes the synthesis and biological characterization of novel
      granisetron derivatives that are antagonists of the human serotonin (5-HT(3)A)
      receptor. Some of these substituted granisetron derivatives showed low nanomolar
      binding affinity and allowed the identification of positions on the granisetron
      core that might be used as attachment points for biophysical tags. A BODIPY
      fluorophore was appended to one such position and specifically bound to 5-HT(3)A
      receptors in mammalian cells.

PMID- 20146482
TI  - Discovery of 4-(4-(2-((5-Hydroxy-1,2,3,4-tetrahydronaphthalen-2
      yl)(propyl)amino)ethyl)piperazin-1-yl)quinolin-8-ol and its analogues as highly
      potent dopamine D2/D3 agonists and as iron chelator: in vivo activity indicates
      potential application in symptomatic and neuroprotective therapy for Parkinson's
      disease.
AB  - The role of iron in the pathogenesis of Parkinson's disease (PD) has been
      implicated strongly because of generation of oxidative stress leading to dopamine
      cell death. In our overall goal to develop bifunctional/multifunctional drugs, we
      designed dopamine D2/D3 agonist molecules with a capacity to bind to iron.
      Binding assays were carried out with HEK-293 cells expressing either D2 or D3
      receptor with tritiated spiperone to evaluate inhibition constants (K(i)).
      Functional activity of selected compounds was carried out with GTPgammaS binding
      assay. SAR results identified compounds (+)-19a and (-)-19b as two potent
      agonists for both D2 and D3 receptors (EC(50) (GTPgammaS); D2 = 4.51 and 1.69 nM
      and D3 = 1.58 and 0.74 nM for (-)-19b and (+)-19a, respectively). In vitro
      complexation studies with 19b demonstrated efficient chelation with iron.
      Furthermore, the deoxyribose assay with 19b demonstrated potent antioxidant
      activity. In PD animal model study, (-)-19b exhibited potent in vivo activity in
      reversing locomotor activity in reserpinized rats and also in producing potent
      rotational activity in 6-OHDA lesioned rats. This reports initial development of
      unique lead molecules that might find potential use in symptomatic and
      neuroprotective treatment of PD.

PMID- 20146484
TI  - Morphological variation and Raman spectroscopy of ZnO hollow microspheres
      prepared by a chemical colloidal process.
AB  - The morphological variation of ZnO hollow miscrospheres was achieved via a two
      step chemical colloidal process. The products were investigated by scanning
      electron microscopy, high-resolution transmission electron microscopy, Raman
      scattering spectroscopy, and photoluminescence spectroscopy. A possible evolution
      mechanism of the ZnO hollow microspheres was discussed. The lattice distortion of
      ZnO hollow microspheres was found on the edge of the surface. Raman spectra
      reveal that the E(2)(high) mode of ZnO hollow microspheres is observed at 432 cm(
      1). A Raman shift of 5 cm(-1) had taken place compared with the original form of
      the ZnO microsphere. This study helps us to understand further the structural
      properties of ZnO hollow microspheres synthesized by a chemical colloidal
      process.

PMID- 20146483
TI  - Development of potent and selective inhibitors of ecto-5'-nucleotidase based on
      an anthraquinone scaffold.
AB  - ecto-5'-Nucleotidase (eN, CD73) plays a major role in controlling extracellular
      adenosine levels. eN inhibitors have potential as novel drugs, for example, for
      the treatment of cancer. In the present study, we synthesized and investigated a
      series of 55 anthraquinone derivatives as potential inhibitors of eN, 11 of which
      are novel compounds and another 11 of which had previously been described but
      have now been synthesized by an improved method. We identified several potent
      inhibitors of rat eN. The most potent compounds were 1-amino-4-[4-fluoro-2
      carboxyphenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (45, PSB-0952,
      K(i) = 260 nM) and 1-amino-4-[2-anthracenylamino]-9,10-dioxo-9,10
      dihydroanthracene-2-sulfonate (52, PSB-0963, 150 nM), with 52 being the most
      potent eN inhibitor described to date. Selected compounds were further
      characterized and found to exhibit a competitive mechanism of inhibition.
      Investigations of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) and
      the P2Y receptor subtypes P2Y(2), P2Y(4), P2Y(6), and P2Y(12) showed that
      compound 45 exhibited the highest degree of selectivity (>150-fold).

PMID- 20146486
TI  - Dilational lateral stress in drying latex films.
AB  - Drying latex films usually experience tensile stress due to the reduction in
      volume. While an unconstrained film would shrink affinely in all three
      dimensions, a coating can only shrink along the vertical and therefore exerts
      tensile stress onto the substrate. Using an instrument capable of producing maps
      of the stress distribution, we found that dilational stress sometimes develops as
      well. The in-plane stress was monitored by spreading the latex dispersion on a
      flexible membrane. Usually, the membrane bends upward under the tensile stress
      exerted by the film, but it may also bend downward. Dilational stress was only
      found with samples showing a strong coffee stain effect, that is, samples in
      which there is a significant lateral flow from the center to the edge while the
      film dries. During drying, particles consolidate first at the edge because of the
      lower height in this region. Continued evaporation from the consolidated region
      results in a water flow toward the edge, exerting a force onto the latex
      particles. At the time, when the network is formed, any single sphere must be in
      a force-balance condition: the network must exert an elastic force onto the
      sphere which just compensates the viscous drag. Pictorially speaking, a spring
      (an elastic network) is created while an external force acts onto it. Once the
      flow stops, the drag force vanishes and the internal stress, which previously
      compensated the drag, expands the film laterally. This phenomenon can lead to
      buckling. Given that lateral flow of liquid while films dry is a rather common
      occurrence, this mode of structure formation should be widespread. It requires
      lateral flow in conjunction with elastic recovery of the particle network.

PMID- 20146485
TI  - Minimizing lateral domain collapse in etched poly(3-hexylthiophene)-block
      polylactide thin films for improved optoelectronic performance.
AB  - Thin films of poly(3-hexylthiophene)-block-polylactide block copolymer exhibiting
      ordered lamellar morphology have been selectively etched to produce structured
      films that could be used in fabrication of idealized bulk heterojunctions for
      organic or hybrid solar energy devices. Etched poly(3-hexylthiophene) films,
      after being rinsed in water to remove degraded polylactide fragments, were dried
      using various drying approaches that reduce or alleviate surface tension forces
      generated during liquid evaporation from the film. As emphasized by atomic force
      microscopy, X-ray diffraction, and emission photoluminescence, a reduction in
      domain collapse leads to improved molecular ordering in the plane perpendicular
      to the substrate and enhanced photoluminescence quenching when paired with
      fullerene C(60) hydroxide electron acceptors.

PMID- 20146488
TI  - 1DE proves its worth... again.

PMID- 20146487
TI  - Regulation of actin polymerization and adhesion-dependent cell edge protrusion by
      the Abl-related gene (Arg) tyrosine kinase and N-WASp.
AB  - Extracellular cues stimulate the Abl family nonreceptor tyrosine kinase Arg to
      promote actin-based cell edge protrusions. Several Arg-interacting proteins are
      potential links to the actin cytoskeleton, but exactly how Arg stimulates actin
      polymerization and cellular protrusion has not yet been fully elucidated. We used
      affinity purification to identify N-WASp as a novel binding partner of Arg. N
      WASp activates the Arp2/3 complex and is an effector of Abl. We find that the Arg
      SH3 domain binds directly to N-WASp. Arg phosphorylates N-WASp on Y256, modestly
      increasing the affinity of Arg for N-WASp, an interaction that does not require
      the Arg SH2 domain. The Arg SH3 domain stimulates N-WASp-dependent actin
      polymerization in vitro, and Arg phosphorylation of N-WASp weakly stimulates this
      effect. Arg and N-WASp colocalize to adhesion-dependent cell edge protrusions in
      vivo. The cell edge protrusion defects of arg-/- fibroblasts can be complemented
      by re-expression of an Arg-yellow fluorescent protein (YFP) fusion, but not by an
      N-WASp binding-deficient Arg SH3 domain point mutant. These results suggest that
      Arg promotes actin-based protrusions in response to extracellular stimuli through
      phosphorylation of and physical interactions with N-WASp.

PMID- 20146490
TI  - Controlled release of volatile fragrance molecules from PEO-b-PPO-b-PEO block
      copolymer micelles in ethanol-water mixtures.
AB  - Active materials that can solubilize in different compartments of a sample show
      release properties which might be of interest in some applications where a
      delayed release of solutes for instance is required. We studied perfume solutes
      in compartments of Pluronic block copolymers of different compositions and
      molecular weights over a range of ethanol-water mixtures. Phase diagrams were
      constructed to identify and map micellar phases, then dynamic light scattering
      was used to characterize the solute-swollen micelles; NMR provided with the
      partition of solutes between solvent and micelles, and equilibrium constants K(c)
      were estimated using headspace analysis. Finally solute-evaporation rates were
      measured by thermogravimetry. We focused on two typical behaviors: when
      solubilization in a micellar compartment occurs, delayed release increased with
      K(c). When solubilization was limited or absent, either because no micelles form
      or, in the presence of micelles, because solubilization was minor or absent,
      delayed release was correspondingly absent.

PMID- 20146489
TI  - Hemolytic activity of a bacterial trehalose lipid biosurfactant produced by
      Rhodococcus sp.: evidence for a colloid-osmotic mechanism.
AB  - A succinoyl trehalose lipid produced by Rhodococcus sp. behaves as a biological
      surfactant and also displays various interesting biological activities. Trehalose
      lipid has been shown to have a great tendency to partition into phospholipid
      membranes; therefore, the characterization of its interaction with biological
      membranes is of central importance. In this work, human red blood cells have been
      used as an experimental model. Trehalose lipid causes the swelling of human
      erythrocytes followed by hemolysis at concentrations well below its critical
      micellar concentration. Kinetic measurements show that, upon addition of
      trehalose lipid, K(+) release precedes that of hemoglobin. Osmotic protectants of
      the appropriate size added to the external medium make it possible to avoid
      hemolysis. The results indicate that trehalose lipid causes the hemolysis of
      human erythrocytes by a colloid-osmotic mechanism, most likely by formation of
      enhanced permeability domains, or "pores" enriched in the biosurfactant, within
      the erythrocyte membrane. Scanning electron microscopy shows trehalose lipid
      induced spherocytosis and echinocytosis of red blood cells, which fits well
      within the framework of the bilayer-couple hypothesis. The presented results
      contribute to establishing a molecular basis for the biological properties of
      this trehalose lipid biosurfactant.

PMID- 20146491
TI  - Thermophoresis and thermoelectricity in surfactant solutions.
AB  - In electrolyte solutions, the differential migration of the ionic species induced
      by the presence of a thermal gradient leads to the buildup of a steady-state
      electric field. Similarly to what happens for the Seebeck effect in solids, the
      sample behaves therefore as a thermocell. Here, we provide clear evidence for the
      presence of thermoelectric fields in liquids by detecting and quantifying their
      strong effects on colloid thermophoresis. Specifically, by contrasting the
      effects of the addition of NaCl or NaOH on the Soret effect of micellar solutions
      of sodium dodecyl sulfate, we show that the presence of highly thermally
      responsive ions such as OH(-) may easily lead to the reversal of particle motion.
      Our experimental results can be quantitatively explained by a simple model that
      takes into account interparticle interactions and explicitly includes the
      micellar electrophoretic transport driven by such a thermally generated electric
      field. The chance of carefully controlling colloid thermophoresis by tuning the
      solvent electrolyte composition may prove to be very useful in microfluidic
      applications and field-flow fractionation methods.

PMID- 20146492
TI  - Theoretical study on adsorption and dissociation of NO2 molecule on Fe(111)
      surface.
AB  - We applied periodic density-functional theory (DFT) to investigate the adsorption
      and dissociation of NO(2) on a Fe(111) surface. The most favorable adsorption
      configuration of NO(2)/Fe(111) is the FeNO(2)(S-mu(3)-N,O,O') configuration with
      NO(2) at the 3-fold-shallow site of the surface, which has an adsorption energy 
      64.59 kcal/mol. Of two geometries of NO(2)/Fe(111) for the stepwise NO(2)
      deoxygenation, one is the most stable structure, FeNO(2)(S-mu(3)-N,O,O'), with
      activation barriers 10.38 and 19.36 kcal/mol to break the first (ON-O bond
      activation) and second (N-O bond activation) nitrogen-oxygen bonds, respectively;
      another configuration FeNO(2)(B-mu(2)-N,O) has a smaller energy barrier (3.88
      kcal/mol) to break the first ON-O bond. All these findings show that NO(2) can
      readily decompose on the Fe(111) surface. The rate constants for the two
      aforementioned processes were also predicted by VTST and RRKM theory, and the
      predicted total rate constants, k(total) (in units of cm(3) molecule(-1) s(-1)),
      can be represented by the equations k(total) = 5.61 x 10(-5)T(-2.060) exp(-0.639
      kcal mol(-1)/RT) at T = 100-1000 K. To acquire insight into the great catalytic
      activity of the Fe(111) surface for the decomposition of NO(2), the nature of the
      interaction between the adsorbate and the substrate is subjected to a detailed
      electronic analysis.

PMID- 20146493
TI  - Conformational studies of covalently grafted poly(ethylene glycol) on modified
      solid matrices using X-ray photoelectron spectroscopy.
AB  - Amine functionalized poly(ethylene glycols) (PEGs) with molecular weights 2000
      and 4000 Da were covalently grafted onto carboxy modified hydrophilic Sephadex
      derivatives and hydrophobic polystyrene derivatives using anhydrous amine
      conjugation methods. Varying PEG surface concentration and layer thickness were
      achieved by controlling the reaction parameters and were analyzed by X-ray
      photoelectron spectroscopy (XPS). C-O intensities obtained from high resolution C
      1s scans were correlated using the standard overlay model to study the grafting
      kinetics as well as conformational properties of grafted polymer chains. A
      detailed and systematic comparison of PEG layer thickness and distance between
      grafted chains with the Flory radius of surface grafted PEG resulted in valuable
      information regarding conformational behavior of the polymer. The influence of
      the nature of the solid matrix on grafting kinetics and conformational properties
      of the grafted polymer chain was also established from the XPS results.

PMID- 20146494
TI  - Interaction between DNA and cationic amphiphiles: a multi-technique study.
AB  - The interaction of cationic amphiphiles with calf thymus DNA has been
      investigated by physicochemical techniques (surface tension, conductometry, UV
      spectroscopy, thermal denaturation) and morphological microscopies (AFM and TEM).
      The cationic molecules were the amphiphiles cetyltrimethylammonium and
      cetyltributylammonium bromides (CTAB and CTBAB, respectively), compared to the
      nonamphiphilic tetramethyl- and tetrabutylammonium bromides (TMAB and TBAB,
      respectively) and, as a transfection-efficient comparison, a commercial
      poliethyleneimine (PEI). As a result, well below their critical micelle
      concentrations (cmc), CTAB and CTBAB showed a peculiar, nonlinear adsorption
      profile with the nucleic acid, which showed a correlation with the melting
      temperatures and morphological changes observed with AFM and TEM microscopies. On
      the other hand, TMAB and TBAB interact much less with the DNA duplexes and do not
      induce any modifications of the structures. The same behavior was observed with
      PEI; however, CTAB and CTBAB proved much less effective in condensing the nucleic
      acid.

PMID- 20146495
TI  - Synthesis and characterization of polypyrrole-palladium nanocomposite-coated
      latex particles and their use as a catalyst for Suzuki coupling reaction in
      aqueous media.
AB  - Polypyrrole-palladium (PPy-Pd) nanocomposite was deposited in situ from aqueous
      solution onto micrometer-sized polystyrene (PS) latex particles. The PS seed
      particles and resulting composite particles were extensively characterized with
      respect to particle size and size distribution, morphology, surface/bulk chemical
      compositions, and conductivity. PPy-Pd nanocomposite loading onto the PS seed
      latex particles was systematically controlled over a wide range (10-60 wt %) by
      changing the weight ratio of the PS latex and PPy-Pd nanocomposite. Pd loading
      was also controlled between 6 and 33 wt %. The conductivity of pressed pellets
      increased with the PPy-Pd nanocomposite loading and four-point probe measurements
      indicated conductivities ranging from 3.0 x 10(-1) to 7.9 x 10(-6) S cm(-1).
      Hollow capsule and broken egg-shell morphologies were observed by
      scanning/transmission electron microscopy after extraction of the PS component
      from the composite particles, which confirmed a PS core and PPy-Pd nanocomposite
      shell morphology. X-ray diffraction confirmed that the production of elemental Pd
      and X-ray photoelectron spectroscopy indicated the existence of elemental Pd on
      the surface of the composite particles. Transmission electron microscopy
      confirmed that nanometer-sized Pd particles were distributed in the shell. The
      nanocomposite particles functioned as an efficient catalyst for Suzuki-type
      coupling reactions in aqueous media for the formation of carbon-carbon bonds.

PMID- 20146496
TI  - Insight into cellular response of plant cells confined within silica-based
      matrices.
AB  - The encapsulation of living plant cells into materials could offer the
      possibility to develop new green biochemical technologies. With the view to
      designing new functional materials, the physiological activity and cellular
      response of entrapped cells within different silica-based matrices have been
      assessed. A fine-tuning of the surface chemistry of the matrix has been achieved
      by the in situ copolymerization of an aqueous silica precursor and a
      biocompatible trifunctional silane bearing covalently bound neutral sugars. This
      method allows a facile control of chemical and physical interactions between the
      entrapped plant cells and the scaffold. The results show that the cell-matrix
      interaction has to be carefully controlled in order to avoid the mineralization
      of the cell wall which typically reduces the bioavailability of nutrients. Under
      appropriate conditions, the introduction of a trifunctional silane (ca. 10%)
      during the preparation of hybrid gels has shown to prolong the biological
      activity as well as the cellular viability of plant cells. The relations of cell
      behavior with some other key factors such as the porosity and the contraction of
      the matrix are also discussed.

PMID- 20146497
TI  - Experimental study of thermodynamic surface characteristics and pH sensitivity of
      silicon dioxide and silicon nitride.
AB  - In this report, we have introduced a revision of the chemical treatment influence
      on the surface thermodynamic properties of silicon dioxide (SiO(2)) and silicon
      nitride (Si(3)N(4)) solid thin layers. Some characterization techniques might be
      used to quantify the thermodynamic properties of solid surface and predict its
      ability in the adhesion phenomenon. In this work, we have used static and dynamic
      contact angle (CA) measurements to characterize both dioxide solid surfaces being
      treated by using the two procedures of cleaning and chemical activation.
      Qualitative and quantitative concepts of analysis, using the Van Oss approach,
      are based on the determination of dioxide surface hydrophilic and hydrophobic
      features and the thermodynamic parameters such as free energy, acid, base, and
      Lewis acid-base surface tension components. Electrochemical capacitance-potential
      measurements were carried out to study the reactivity of both silicon dioxide and
      silicon nitride surfaces for pH variation. Furthermore, the surface roughness of
      these insulators was examined by using the contact angle hysteresis (CAH)
      measurements and atomic force microscopy (AFM). It was concluded that CA
      technique can be used as a suitable and base method for the understanding of
      surface wettability and for the control of surface wetting behavior.

PMID- 20146498
TI  - Surface functionalization of zinc oxide by carboxyalkylphosphonic acid self
      assembled monolayers.
AB  - Two carboxyalkylphosphonic acids (HOOC(CH(2))(n)P(O)(OH)(2), n = 2 for 3-PPA and
      n = 9 for 10-PDA) have been deposited onto 1D zinc oxide (ZnO) nanowires and bare
      ZnO wafers to form stable self-assembled monolayers (SAMs). The samples were
      systematically characterized using wettability, atomic force microscopy (AFM),
      Fourier transform infrared spectroscopy (FT-IR), and X-ray photoelectron
      spectroscopy (XPS). 3-PPA was bound to the ZnO surfaces mainly through the CO(2)H
      headgroup, and 10-PDA formed self-assembled monolayers on the nanoscaled ZnO
      surface through the PO(3)H(2) headgroups. To verify the potential utilization of
      the functionalized surfaces in the construction of biosensors or bioelectronics,
      IgG (immunoglobulin G) protein immobilization through SAM bridging was
      demonstrated. This work expands the application of phosphonic acid-based surface
      functionalization on sensing and optoelectronic devices.

PMID- 20146499
TI  - Atomistic simulation of NO dioxygenation in group I truncated hemoglobin.
AB  - NO dioxygenation, i.e., the oxidation of nitric oxide to nitrate by oxygen-bound
      truncated hemoglobin (trHbN) is studied using reactive molecular dynamics
      simulations. This reaction is an important step in a sequence of events in the
      overall NO detoxification reaction involving trHbN. The simulations (
      approximately 160 ns in total) reveal that the reaction favors a pathway
      including (i) NO binding to oxy-trHbN, followed by (ii) rearrangement of
      peroxynitrite-trHbN to nitrato-trHbN, and finally (iii) nitrate dissociation from
      nitrato-trHbN. Overall, the reactions occur within tens of picoseconds and the
      crossing seam of the reactant and product are found to be broad. The more
      conventional pathway, where the peroxynitrite-trHbN complex undergoes peroxide
      cleavage to form free NO(2) and oxo-ferryl trHbN, is found to be too slow due to
      a considerable barrier involved in peroxide bond dissociation. The energetics of
      this step is consistent with earlier electronic structure calculations and make
      this pathway less likely. The role of Tyr33 and Gln58 in the NO dioxygenation has
      been investigated by studying the reaction in mutants of trHbN. The mutation
      study suggests that residues Tyr33 and Gln58 preorient the reactive ligands
      through a highly dynamical H-bonding network which facilitates the reaction. In
      particular, the Y33A mutation leads to a significant retardation in NO
      dioxygenation, in agreement with experiments which reveal a strong influence of
      the protein environment on the reaction rate.

PMID- 20146500
TI  - Use of force spectroscopy to investigate the adhesion of living adherent cells.
AB  - The use of force spectroscopy to study the adhesion of living fibroblasts to
      their culture substrate was investigated. Both primary fibroblasts (PEMF) and a
      continuous cell line (3T3) were studied on quartz surfaces. Using a fibronectin
      coated AFM cantilever, it was possible to detach a large proportion of the 3T3
      cells from the quartz surfaces. Their adhesion to the quartz surface and the
      effects of topography on this adhesion could be quantified. Three parameters
      characteristic of the adhesion were measured: the maximum force of detachment,
      the work of adhesion, and the distance of detachment. Few PEMF cells were
      detached under the same experimental conditions. The potential and limitations of
      this method in measuring cell/surface interactions for adherent cells are
      discussed.

PMID- 20146501
TI  - Poly(ethylene glycol) adlayers immobilized to metal oxide substrates through
      catechol derivatives: influence of assembly conditions on formation and
      stability.
AB  - We have investigated five different poly(ethylene glycol) (PEG, 5 kDa) catechol
      derivatives in terms of their spontaneous surface assembly from aqueous solution,
      adlayer stability, and resistance to nonspecific blood serum adsorption as a
      function of the type of catechol-based anchor, assembly conditions (temperature,
      pH), and type of substrate (SiO(2), TiO(2), Nb(2)O(5)). Variable-angle
      spectroscopic ellipsometry (VASE) was used for layer thickness evaluation, X-ray
      photoelectron spectroscopy (XPS) for layer composition, and ultraviolet-visible
      optical spectroscopy (UV-vis) for cloud point determination. Polymer surface
      coverage was influenced by the type of catechol anchor, type of the substrate, as
      well as pH and temperature (T) of the assembly solution. Furthermore, it was
      found to be highest for T close to the cloud point (T(CP)) and pH of the assembly
      solution close to pK(a1) (dissociation constant of the first catechol hydroxy
      group) of the polymer and to the isoelectric point (IEP) of the substrate. T(CP)
      turned out to depend on not only the ionic strength of the assembly solution, but
      also the type of catechol derivative and pH. PEG-coating dry thickness above 10 A
      correlated with low serum adsorption. We therefore conclude that optimum coating
      protocols for catechol-based polymer assembly at metal oxide interfaces have to
      take into account specific physicochemical properties of the polymer, anchor, and
      substrate.

PMID- 20146502
TI  - Water-soluble triarylphosphines as biomarkers for protein S-nitrosation.
AB  - S-Nitrosothiols (RSNOs) represent an important class of post-translational
      modifications that preserve and amplify the actions of nitric oxide and regulate
      enzyme activity. Several regulatory proteins are now verified targets of cellular
      S-nitrosation, and the direct detection of S-nitrosated residues in proteins has
      become essential to better understand RSNO-mediated signaling. Current RSNO
      detection depends on indirect assays that limit their overall specificity and
      reliability. Herein, we report the reaction of S-nitrosated cysteine,
      glutathione, and a mutated C165S alkyl hydroperoxide reductase with the water
      soluble phosphine tris(4,6-dimethyl-3-sulfonatophenyl)phosphine trisodium salt
      hydrate (TXPTS). A combination of NMR and MS techniques reveals that these
      reactions produce covalent S-alkylphosphonium ion adducts (with S-P(+)
      connectivity), TXPTS oxide, and a TXPTS-derived aza-ylide. Mechanistically, this
      reaction may proceed through an S-substituted aza-ylide or the direct
      displacement of nitroxyl from the RSNO group. This work provides a new means for
      detecting and quantifying S-nitrosated species in solution and suggests that
      phosphines may be useful tools for understanding the complex physiological roles
      of S-nitrosation and its implications in cell signaling and homeostasis.

PMID- 20146503
TI  - Limonoids and tirucallane derivatives from the seeds of a krishna mangrove,
      Xylocarpus moluccensis.
AB  - Six new phragmalins, moluccensins H-M (1-6), two new andirobin-type limonoids,
      moluccensins N and O (7, 8), and two new tirucallane derivatives, moluccensins P
      and Q (9, 10), were isolated from seeds of an Indian mangrove, Xylocarpus
      moluccensis, together with the known compound 3beta,22S-dihydroxytirucalla-7,24
      dien-23-one. The structures of these compounds were established on the basis of
      spectroscopic data. Moluccensins H-L were phragmalins with a C-30 carbonyl group,
      and moluccensin M was a unique ring-D-opened 16-norphragmalin. Moluccensins H-J
      possess conjugated Delta(8,9) and Delta(14,15) double bonds, moluccensins K and L
      contain a Delta(8,14) double bond, and moluccensin M has a characteristic C(15)
      C(30) linked five-membered lactone ring. Moluccensins H and I showed moderate
      insecticidal activity against the fifth instar larvae of Brontispa longissima
      (Gestro) at a concentration of 100 mg/L.

PMID- 20146504
TI  - Tetrapeptides possessing a unique skeleton, JBIR-34 and JBIR-35, isolated from a
      sponge-derived actinomycete, Streptomyces sp. Sp080513GE-23.
AB  - Two new modified indole-containing peptides, JBIR-34 (1) and JBIR-35 (2), were
      isolated from the fermentation broth of a sponge-derived actinomycete identified
      by phylogenetic methods as a Streptomyces sp. (strain Sp080513GE-23). The planar
      structures of 1 and 2 were assigned on the basis of 1D and 2D NMR spectroscopy
      and MS analyses. Further, the absolute configurations of the amino acid residues
      were determined using Marfey's method.

PMID- 20146505
TI  - Ta3N5 nanotube arrays for visible light water photoelectrolysis.
AB  - Tantalum nitride (Ta3N5) has a band gap of approximately 2.07 eV, suitable for
      collecting more than 45% of the incident solar spectrum energy. We describe a
      simple method for scale fabrication of highly oriented Ta3N5 nanotube array
      films, by anodization of tantalum foil to achieve vertically oriented tantalum
      oxide nanotube arrays followed by a 700 degrees C ammonia anneal for sample
      crystallization and nitridation. The thin walled amorphous nanotube array
      structure enables transformation from tantalum oxide to Ta3N5 to occur at
      relatively low temperatures, while high-temperature annealing related structural
      aggregation that commonly occurs in particle films is avoided. In 1 M KOH
      solution, under AM 1.5 illumination with 0.5 V dc bias typical sample (nanotube
      length approximately 240 nm, wall thickness approximately 7 nm) visible light
      incident photon conversion efficiencies (IPCE) as high as 5.3% were obtained. The
      enhanced visible light activity in combination with the ordered one-dimensional
      nanoarchitecture makes Ta3N5 nanotube arrays films a promising candidate for
      visible light water photoelectrolysis.

PMID- 20146507
TI  - Symmetry breaking in gold-silica-gold multilayer nanoshells.
AB  - We present a computational study of the plasmonic properties of gold-silica-gold
      multilayer nanoshells with the core offset from the center. Symmetry breaking,
      due to the core offset, makes plasmon resonances that are dark in concentric
      geometries visible. Applying plasmon hybridization theory, we explain the origin
      of these resonances from the interactions of an admixture of both primitive and
      multipolar modes between the core and the shell. The interactions introduce a
      dipole moment into the higher order modes and significantly enhance their
      coupling efficiency to light. To elucidate the symmetry breaking effect, we link
      the geometrical asymmetry to the asymmetrical distribution of surface charges and
      demonstrate illustratively the diminishing multipolar characteristic and
      increasing dipolar characteristic of the higher order modes. The relative
      amplitudes of the modes are qualitatively related by visual examination of the
      dipolar component in the surface charge distributions. Using polarization
      dependent surface charge plots, we illustrate two distinct mode configurations
      despite their spectral similarities. We further demonstrate a trend of increasing
      absorption relative to scattering as the resonant wavelength red shifts in
      response to a larger core offset.

PMID- 20146506
TI  - Self-assembled gold nanoparticle molecular probes for detecting proteolytic
      activity in vivo.
AB  - Target-activatable fluorogenic probes based on gold nanoparticles (AuNPs)
      functionalized with self-assembled heterogeneous monolayers of dye-labeled
      peptides and poly(ethylene glycol) have been developed to visualize proteolytic
      activity in vivo. A one-step synthesis strategy that allows simple generation of
      surface-defined AuNP probe libraries is presented as a means of tailoring and
      evaluating probe characteristics for maximal fluorescence enhancement after
      protease activation. Optimal AuNP probes targeted to trypsin and urokinase-type
      plasminogen activator required the incorporation of a dark quencher to achieve 5-
      to 8-fold signal amplification. These probes exhibited extended circulation time
      in vivo and high image contrast in a mouse tumor model.

PMID- 20146508
TI  - An enantioselective approach to highly substituted tetrahydrocarbazoles through
      hydrogen bonding-catalyzed cascade reactions.
AB  - A hydrogen bonding-mediated double Michael addition-aromatization cascade of 2
      propenylindoles and nitroolefins has been disclosed. The methodology allows an
      efficient synthesis of diverse and structurally complex tetrahydrocarbazoles in
      good to excellent enantioselectivities and diastereoselectivities.

PMID- 20146509
TI  - Force field optimization using dynamics and ensemble averaged data: vibrational
      spectra and relaxation in bound MbCO.
AB  - Force field parameters are ingredients for realistic atomistic simulations of gas
      and condensed-phase systems. Here we discuss the effect of including averaged
      data from explicit MD simulations in optimizing potential energy functions. It is
      shown that vibrational frequencies (FeC and CO stretch and FeCO bend) and CO
      vibrational relaxation times ((v = 1) --> (v = 0) (T(10)) and (v = 2) --> (v = 1)
      (T(21))) in the active site of CO-bound myoglobin (MbCO) can be well represented
      with a single set of force field parameters. It is further demonstrated that
      parameters fitted in a subsystem of MbCO comprising the CO ligand, heme group and
      proximal histidine, are transferable to investigating the full protein and to
      providing quantitatively correct results. In particular, it is possible to
      calculate the CO and FeC stretch and the FeCO bending frequency to within
      approximately 5%; the relaxation time of the first vibrationally excited state
      including quantum corrections of T(10) approximately 25 ps is calculated close to
      the experimental value (17 ps), and the ratio T(10)/T(21) approximately 2 agrees
      favorably with experimental estimates. In contrast, following the more
      traditional approach of fitting frequencies from analyzing the Hessian matrix
      leads to a force field that captures frequencies correctly but not relaxation of
      vibrations.

PMID- 20146510
TI  - Synthesis and supramolecular organization of regioregular polythiophene block
      oligomers.
AB  - The self-assembly of functional polythiophenes was studied by a bottom-up
      approach "from molecule to polymer". The synthesis and the X-ray structure of 2,5
      dibromo-3-styryl and 3-2',3',4',5',6'-pentafluorostyryl-thiophenes revealed a
      supramolecular arrangement controlled by pi-pi interactions between the aromatic
      rings. A [2 + 2] photocyclization reaction in the solid state of (E)-1-2',5'
      dibromo-3'-thienyl-2-pentafluorophenylethene triggers the formation of a rare
      cycloadduct comprising thiophene rings. The X-ray analysis confirmed its rctt
      stereochemistry. The synthesis of P3HT-b-P3ST and P3HT-b-P3STF block oligomers
      was achieved by a GRIM method in good yields. An indirect proof of well-defined
      nanostructured organization was provided by the partial photocyclization of
      pendant styryl moieties under UV irradiation.

PMID- 20146511
TI  - Micellization activity of the natural lipopeptide [Glu1, Asp5] surfactin-C15 in
      aqueous solution.
AB  - Surface tension, small angle neutron scattering (SANS), freeze-fracture
      transmission electron microscopy (FF-TEM), and circular dichroism (CD) have been
      used to study the self-aggregation properties of the natural lipopeptide [Glu(1),
      Asp(5)] surfactin-C15 in 0.01 M phosphate buffer solution (PBS) at pH 7.4. It has
      been found that the critical micelle concentration (cmc) of surfactin is 1.54 x
      10(-5) M, the surface tension at the cmc (sigma(cmc)) is 27.7 mN/m, and the area
      per molecule at the air-water interface is 107.8 A(2). Surfactin molecules adopt
      a beta-sheet conformation already at low concentrations. This feature probably
      makes it surface-active at such low concentrations. From SANS and FF-TEM results,
      it is seen that surfactin exhibits a strong self-assembly ability to form sphere
      like micelles and some larger aggregates even at the rare low concentration. The
      aggregation number of sphere-like micelles is much smaller than that for
      conventional surfactants of similar alkyl chain length.

PMID- 20146512
TI  - Deuterated water effect in a room temperature ionic liquid: N,N-diethyl-N-methyl
      N-2-methoxyethyl ammonium tetrafluoroborate.
AB  - A deuterated water effect in the room temperature ionic liquid (RTIL) N,N-diethyl
      N-methyl-N-2-methoxyethyl ammonium tetrafluoroborate, [DEME][BF(4)], is observed
      in its crystal domain structures; crystallization temperature, T(c); crystal
      superstructures; and volume contractions. The above effect, seen in [DEME][BF(4)]
      0.9 mol % H(2)O mixtures, is reduced in 1.0 mol % 0.75 H(2)O x 0.25 D(2)O and 0.9
      mol % 0.5 H(2)O x 0.5 D(2)O mixtures and is completely suppressed in 1.3 mol %
      D(2)O mixtures. Interestingly, T(c) decreased systemically with D substitutions
      of water. In contrast to the crystal state, it was found that there is no
      difference between H(2)O and D(2)O mixtures in the liquid state, on the basis of
      X-ray diffraction patterns. At around 80-90 mol % H(2)O, the intermolecular
      correlation of [DEME][BF(4)] as a local structure changes to that of bulk water.

PMID- 20146513
TI  - Probing electron density of H-bonding between cation-anion of imidazolium-based
      ionic liquids with different anions by vibrational spectroscopy.
AB  - Attenuated total reflection infrared spectroscopy and density functional theory
      calculation have been employed to study the spectral properties of imidazolium
      based ionic liquids (ILs) with different anions. ILs based on 1-butyl-3
      methylimidazolium cation with different anions, OH(-), CF(3)CO(2)(-), HSO(4)(-),
      H(2)PO(4)(-), Cl(-), PF(6)(-), and BF(4)(-), are investigated in the present
      work. It has been shown that the C(2)-H stretching vibration of the imidazolium
      ring is closely related to the electron density of H-bonding between the two
      closest cations and anions for pure ILs. The electron density of H-bonding
      between cation and anion with different anions decreases in the order [OH](-) >
      [H(2)PO(4)](-) > [HSO(4)](-) > [CF(3)CO(2)](-) > [Cl](-) > [BF(4)](-) > [PF(6)](
      ). For aqueous ILs, with increasing water content, the aromatic C-H stretching
      vibration of the imidazolium cation showed systematic blue-shifts. Especially for
      BmimOH, the nu(C(2))(-H) undergoes a drastic blue-shift by 58 cm(-1), suggesting
      that the formation of the strong hydrogen bonds O-H...O may greatly weaken the
      electron density of H-bonding between the cation and anion of ILs.

PMID- 20146514
TI  - Simple geometrical interpretation of the linear character for the Zeno-line and
      the rectilinear diameter.
AB  - The unified geometrical interpretation of the linear character of the Zeno-line
      (unit compressibility line Z = 1) and the rectilinear diameter is proposed. We
      show that recent findings about the properties of the Zeno-line and striking
      correlation with the rectilinear diameter line as well as other empirical
      relations can be naturally considered as the consequences of the projective
      isomorphism between the real molecular fluids and the lattice gas (Ising) model.

PMID- 20146515
TI  - Ion selectivity of alpha-hemolysin with beta-cyclodextrin adapter. II. Multi-ion
      effects studied with grand canonical Monte Carlo/Brownian dynamics simulations.
AB  - In a previous study of ion selectivity of alpha-hemolysin (alphaHL) in complex
      with beta-cyclodextrin (betaCD) adapter, we calculated the potential of mean
      force (PMF) and characterized the self-diffusion coefficients of isolated K(+)
      and Cl(-) ions using molecular dynamics simulations (Y. Luo et al., "Ion
      Selectivity of alpha-Hemolysin with beta-Cyclodextrin Adapter: I. Single Ion
      Potential of Mean Force and Diffusion Coefficient"). In the present effort, these
      results pertaining to single isolated ions in the wide aqueous pore are extended
      to take into account multi-ion effects. The grand canonical Monte Carlo/Brownian
      dynamics (GCMC/BD) algorithm is used to simulate ion currents through the wild
      type alphaHL ion channel, as well as two engineered alphaHL mutants, with and
      without the cyclic oligosaccaride betaCD lodged in the lumen of the pore. The
      GCMC/BD current-voltage curves agree well with experimental results and show that
      betaCD increases the anion selectivity of alphaHL. Comparisons between multi-ion
      PMFs from GCMC/BD simulations and single-ion PMFs demonstrate that multi-ion
      effects and pore shape are crucial for explaining this behavior. It is concluded
      that the narrow betaCD adapter increases the anion selectivity of alphaHL because
      it reduces the pore radius locally, which decreases the ionic screening and the
      dielectric shielding of the strong electrostatic field induced by a nearby ring
      of positively charged alphaHL side chains.

PMID- 20146516
TI  - The crystalline nanocluster phase as a medium for structural and spectroscopic
      studies of light absorption of photosensitizer dyes on semiconductor surfaces.
AB  - The crystalline nanocluster phase, in which nanoscale metal oxide clusters are
      self-assembled in three-dimensional periodic arrays, is described. The
      crystalline assembly of nanoparticles functionalized with technologically
      relevant ligands offers the opportunity to obtain unambiguous structural
      information that can be combined with theoretical calculations based on the known
      geometry and used to interpret spectroscopic and other information. A series of
      Ti/O clusters up to approximately 2.0 nm in diameter have been synthesized and
      functionalized with the adsorbents catechol and isonicotinic acid. Whereas the
      isonicotinate is always adsorbed in a bridging monodentate mode, four different
      adsorption modes of catechol have been identified. The particles show a
      significantly larger variation of the Ti-O distances than observed in the known
      TiO(2) phases and exhibit both sevenfold overcoordination and five- and fourfold
      undercoordination of the Ti atoms. Theoretical calculations show only a moderate
      dependence of the catecholate net charge on the geometry of adsorption. All of
      the catechol-functionalized clusters have a deep-red color due to penetration of
      the highest occupied catechol levels into the band gap of the Ti/O particles.
      Spectroscopic measurements of the band gap of the Ti(17) cluster are in good
      agreement with the theoretical values and show a blue shift of approximately 0.22
      eV relative to those reported for anatase nanoparticles.

PMID- 20146517
TI  - Observation of redox-state-dependent reversible local structural change of
      ferrocenyl-terminated molecular island by electrochemical frequency modulation
      AFM.
AB  - Electroactive ferrocenylundecanethiol (FcC(11)H(22)SH) islands embedded in an n
      decanethiol (C(10)H(21)SH) self-assembled monolayer (SAM) matrix on Au(111) were
      studied under potential control in 0.1 M HClO(4) aqueous solution using newly
      developed electrochemical frequency-modulation atomic force microscopy (EC-FM
      AFM). The apparent height of the Fc islands from the surface of the matrix SAM
      increased by about 0.44 nm accompanied by the oxidation of the terminal Fc
      groups. This potential-dependent reversible change can be explained by formation
      of an ionic double layer where ClO(4)(-) ions are strongly bound on the Fc(+)
      groups. Simultaneous measurements of energy dissipation, which corresponds to the
      energy to keep the cantilever's vibrational amplitude constant, revealed distinct
      change in the magnitude by the oxidation state of the Fc groups. These results
      indicate that localized charge at an electrode/electrolyte solution interface can
      be identified, and microscopic information on the electric double layer at the
      interface is available by using EC-FM-AFM.

PMID- 20146519
TI  - Bowman-Birk proteinase inhibitor from Cajanus cajan seeds: purification,
      characterization, and insecticidal properties.
AB  - A red gram proteinase inhibitor (RgPI) was purified from red gram ( Cajanus cajan
      ) seeds by using ammonium sulfate precipitation and ion-exchange, affinity, and
      gel filtration chromatography. SDS-PAGE under nonreducing condition revealed two
      protein bands with molecular masses of approximately 8.5 and approximately 16.5
      kDa corresponding to monomeric and dimeric forms of RgPI, respectively.
      Similarly, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)
      mass spectrometry also confirmed the presence of dimer as well as other
      oligomeric forms: trimer, tetramer, and pentamer. Reduction of RgPI with
      dithiothreitol (DTT) led to the dissociation of the dimeric and oligomeric forms.
      Native-PAGE and two-dimensional gel electrophoresis indicated the existence of
      isoinhibitors with pI values of 5.95, 6.25, 6.50, 6.90, and 7.15, respectively.
      The MALDI-TOF-TOF mass spectrum and N-terminal sequence 'DQHHSSKACC' suggested
      that the isolated RgPI is a member of the Bowman-Birk inhibitor family. RgPI
      exhibited noncompetitive type inhibitory activity against bovine pancreatic
      trypsin and chymotrypsin, with inhibition constants of 292 and 2265 nM,
      respectively. It was stable up to a temperature of 80 degrees C and was active
      over a wide pH range between 2 and 12. However, reduction with DTT or 2
      mercaptoethanol resulted in loss of inhibitory activity against trypsin and
      chymotrypsin. It also decreased the activity of larval midgut trypsin-like
      proteinases in Manduca sexta . Its insecticidal property was further confirmed by
      reduction in the growth and development of these larvae, when supplemented in the
      diet.

PMID- 20146518
TI  - Photo-cross-linked PDMSstar-PEG hydrogels: synthesis, characterization, and
      potential application for tissue engineering scaffolds.
AB  - Inorganic-organic hydrogels with tunable chemical and physical properties were
      prepared from methacrylated star polydimethylsiloxane (PDMS(star)-MA) and
      diacrylated poly(ethylene glycol) (PEG-DA) for use as tissue engineering
      scaffolds. A total of 18 compositionally unique hydrogels were prepared by photo
      cross-linking, varying weight ratios of PEG-DA and PDMS(star)-MA of different
      molecular weights (M(n)): PEG-DA (M(n) = 3.4k and 6k g/mol) and PDMS(star)-MA
      (M(n) = 1.8k, 5k, and 7k g/mol). Introduction of PDMS(star)-MA caused formation
      of discrete PDMS-enriched microparticles dispersed within the PEG matrix. The
      swelling ratio, mechanical properties in tension and compression, nonspecific
      protein adhesion, controlled introduction of bioactivity, and cytotoxicity of
      hydrogels were studied. This library of inorganic-organic hydrogels with tunable
      properties provides a useful platform to study the effect of scaffold properties
      on cell behavior.

PMID- 20146520
TI  - Preparation of curcumin sub-micrometer dispersions by high-pressure
      homogenization.
AB  - High-pressure homogenization (HPH) processing has been used to increase the water
      dispersity of curcumin, a popular spice and coloring and antioxidant agent, which
      shows anti-inflammatory and anti-cancer properties but poor water solubility and
      oral bioavailability. The optimized HPH treatment was achieved at the combined
      conditions of temperature at 2 degrees C, pressure at 150 MPa, and 10 HPH cycles.
      The mechanism behind the improved water dispersity of curcumin by HPH treatment
      was interpreted as a result of the reduced curcumin particle sizes and
      crystallinity caused by mechanical stresses, which were verified by particle size
      measurements, differential scanning calorimetry (DSC) and X-ray diffraction (XRD)
      results. Spray drying of maltodextrin (MD)-entrapped curcumin can also increase
      the water dispersity of curcumin. A combination of HPH treatment and spray drying
      using MD exhibits a faster curcumin dissolution while retaining a higher water
      dispersity of curcumin than curcumin prepared by either spray drying using MD
      alone or the combination of HPH and freeze-drying using MD, suggesting that the
      combination of HPH processing with spray drying would be an excellent processing
      method for curcumin-based functional food products.

PMID- 20146521
TI  - Acetylcholinesterase inhibitory activity of volatile oil from Peltophorum
      dasyrachis Kurz ex Bakar (yellow batai) and Bisabolane-type sesquiterpenoids.
AB  - In this study, the chemical compositions and acetylcholinesterase (AChE)
      inhibitory activitiy of the volatile oil from the bark of Peltophorum dasyrachis
      Kurz ex Bakar (yellow batai) were evaluated. As a result, 68 compounds,
      accounting for 88.0% of the total oil, were identified. The main characteristic
      constituent in P. dasyrachis was isolated by silica gel column chromatography and
      found to be a sesquiterpenoid, (+)-(S)-ar-turmerone (1). In the AChE inhibitory
      assay, the volatile oil showed potent inhibitory activity with the IC(50) value
      of 83.2 +/- 2.8 microg/mL. Among the volatile oil components and characteristic
      sesquiterpenoids, (+)-(S)-ar-turmerone (1) and (+)-(S)-dihydro-ar-turmerone (2)
      were potent compounds, inhibiting AChE in a dose-dependent manner, with IC(50)
      values of 191.1 +/- 0.3 and 81.5 +/- 0.2 microM, respectively. (+)-(S)-Dihydro-ar
      turmerone (2), in particular, was found to be the most potent AChE inhibitor.
      Also, bisabolane-type sesquiterpenoid derivatives, (+)-(7S,9S)-ar-turmerol (3),
      (+)-(7S,9R)-ar-turmerol (4), (+)-(7S,9S)-dihydro-ar-turmerol (5), (+)-(7S,9R)
      dihydro-ar-turmerol (6), (+)-(S)-ar-curcumene (7), and (+)-(S)-dihydro-ar
      curcumene (8), were synthesized and tested for their AChE inhibitory effect, and
      their structure-activity relationships were evaluated. All sesquiterpenoids
      exhibited AChE inhibitory activity. The order of AChE inhibitory potency by
      bisabolane-type sesquiterpenoids was as follows: ketones > alcohols >
      hydrocarbons. Furthermore, the inhibition kinetics analyzed by Dixon plots
      indicated that (+)-(S)-ar-turmerone (1) is a competitive inhibitor, with a K(i)
      value of 882.1 +/- 2.1 microM, whereas (+)-(S)-dihydro-ar-turmerone (2) is a non
      competitive inhibitor.

PMID- 20146522
TI  - Directed formation of an organotin sulfide cavitand and its transformation into a
      rugby-ball-like capsule.
AB  - We report the systematic synthesis and thorough characterization of a discrete
      organotin sulfide cavitand, [R(B)(4)Sn(12)S(20)] {1, R(B) = 1,5-bis[(E)-2-(4
      methylpentan-2-ylidene)hydrazinyl]naphthalene}, which readily undergoes a unique
      transformation into a stable, rugby-ball-like capsule,
      [R(B)(3)Sn(6)S(8)][(SnCl(3))(2)] (2), upon addition of a protic acid. DMF
      molecules are embedded within the cavities of both compounds by hydrogen-bonding
      interactions, spotlighting the title compounds with respect to molecular
      containment.

PMID- 20146523
TI  - Connecting the molecular scale to the continuum scale for diffusion processes in
      smectite-rich porous media.
AB  - In this paper, we address the manner in which the continuum-scale diffusive
      properties of smectite-rich porous media arise from their molecular- and pore
      scale features. Our starting point is a successful model of the continuum-scale
      apparent diffusion coefficient for water tracers and cations, which decomposes it
      as a sum of pore-scale terms describing diffusion in macropore and interlayer
      "compartments." We then apply molecular dynamics (MD) simulations to determine
      molecular-scale diffusion coefficients D(interlayer) of water tracers and
      representative cations (Na(+), Cs(+), Sr(2+)) in Na-smectite interlayers. We find
      that a remarkably simple expression relates D(interlayer) to the pore-scale
      parameter delta(nanopore) <= 1, a constrictivity factor that accounts for the
      lower mobility in interlayers as compared to macropores: delta(nanopore) =
      D(interlayer)/D(0), where D(0) is the diffusion coefficient in bulk liquid water.
      Using this scaling expression, we can accurately predict the apparent diffusion
      coefficients of tracers H(2)0, Na(+), Sr(2+), and Cs(+) in compacted Na-smectite
      rich materials.

PMID- 20146524
TI  - Diameter selectivity of protein encapsulation in carbon nanotubes.
AB  - Biomolecular-carbon nanotube (CNT) complexes are of great importance in
      biological and biomedical devices, and recently spontaneous encapsulation of
      biomolecules into CNTs has attracted great interest. In this work, we explored
      the diameter selectivity of the protein encapsulation in CNTs via molecular
      dynamics simulations, and the free energy changes of the systems were calculated
      for mechanism exploration. It is proved that there is an optimal tube size which
      provides the most effective encapsulation for a given protein molecule, and the
      encapsulations in the overlarge and overcrowded tubes are hindered by different
      factors based on the analysis of system energy contribution. In addition, the
      significance of the solvents for the system is also of concern.

PMID- 20146525
TI  - Brillouin scattering study of polyethylene glycol/water system below
      crystallization temperature.
AB  - We present the results of a Brillouin scattering experiment on aqueous mixtures
      of polyethylene glycol polymer cooled below their crystallization temperature.
      The shape of the registered spectrum changed considerably when the phase
      transition occurs. The Brillouin profile consisted of two peaks which has been
      interpreted as a result of the scattering of light on the local regions
      exhibiting different compressibility. Examination of the temperature dependence
      of the two Brillouin peak positions allows the identification of the specific
      microstructures present in the studied system. The existence of a complexlike
      hydration structure, stable against dilution and temperature agitation, was
      suggested. The nature and the behavior of the hydration complex is discussed in
      view of the earlier investigations in similar systems.

PMID- 20146526
TI  - Photoselective ultrafast investigation of xanthorhodopsin and its carotenoid
      antenna salinixanthin.
AB  - Excited-state dynamics of xanthorhodopsin (XR) and of salinixanthin (SX) in
      ethanol were investigated by ultrafast pump-hyperspectral probe spectroscopy.
      Following excitation to the strongly allowed S(2) state of the SX chromophore,
      transient spectra were recorded photoselectively in the range 430-850 nm. Global
      kinetic analysis of these data shows the following. (1) Efficient energy transfer
      from S(2) of the SX in XR to its retinal moiety is verified here. The lifetime of
      S(2) in SX is, however, determined to be approximately 20 fs, much shorter than
      previously reported. (2) Branching ratios of excitation transfer from S(2) to
      S(1), to S*, and to retinal in XR are measured leading to species associated
      difference spectra (SADS) for all the states involved. Strong protein effects are
      detected on these branching probabilities. (3) S(1) and S* absorption bands in
      both systems exhibit anisotropy well below the expected r = 0.4, indicating an
      angle of approximately 25 degrees between the S(0) --> S(2) and S(1) --> S(n)/S* 
      -> S(n) transition dipoles. The latter allows confident assignment of the debated
      S* absorption band to an excited state of SX, and not to "hot" S(0). In light of
      the extremely fast IC from S(2) to lower excited singlets, possible involvement
      of ballistic IC in SX, and of coherent energy transfer in XR, are discussed.

PMID- 20146527
TI  - Photobiological activity of Ru(II) dyads based on (pyren-1-yl)ethynyl derivatives
      of 1,10-phenanthroline.
AB  - Several mononuclear Ru(II) dyads possessing 1,10-phenanthroline-appended
      pyrenylethynylene ligands were synthesized, characterized, and evaluated for
      their potential in photobiological applications such as photodynamic therapy
      (PDT). These complexes interact with DNA via intercalation and photocleave DNA in
      vitro at submicromolar concentrations when irradiated with visible light
      (lambda(irr) > or = 400 nm). Such properties are remarkably sensitive to the
      position of the ethynylpyrenyl substituent on the 1,10-phenanthroline ring, with
      3-substitution showing the strongest binding under all conditions and causing the
      most deleterious DNA damage. Both dyads photocleave DNA under hypoxic conditions,
      and this photoactivity translates well to cytotoxicity and photocytotoxicity
      models using human leukemia cells, where the 5- and 3-substituted dyads show
      photocytotoxicity at 5-10 microM and 10-20 microM, respectively, with minimal, or
      essentially no, dark toxicity at these concentrations. This lack of dark
      cytotoxicity at concentrations where significant photoactivity is observed
      emphasizes that agents with strong intercalating units, previously thought to be
      too toxic for phototherapeutic applications, should not be excluded from the
      arsenal of potential photochemotherapeutic agents under investigation.

PMID- 20146528
TI  - An acyl group makes a difference in the reactivity patterns of cytochrome P450
      catalyzed N-demethylation of substituted N,N-dimethylbenzamides-high spin
      selective reactions.
AB  - This paper addresses the experimentally observed mechanistic differences between
      the cytochrome P450-catalyzed N-demethylation of substituted N,N-dimethylanilines
      (DMA) and of N,N-dimethylbenzamides (DMBA). The two reactions of these substrates
      are initiated by C-H activation of the methyl groups on the nitrogen. Thus, the
      DMA reactions exhibit small deuterium kinetic isotope effects (KIEs), and these
      KIEs and the corresponding reaction rates exhibit a linear response to the
      electronic nature of the para substituent. By contrast, the DMBA reactions
      exhibit large KIEs; the KIEs and reaction rates do not at all respond to the
      nature of the para substituent. Accordingly, the present paper uses density
      functional theoretical calculations to address these reactivity patterns in para
      substituted DMBA and compare these results to those obtained for the DMA
      reactions previously (Wang, Y.; Kumar, D.; Yang, C. L.; Han, K. L.; Shaik, S. J.
      Phys. Chem. B 2007, 111, 7700). The theoretical calculations reproduce the
      experimental trends of narrow variations in rates and KIEs. It is shown that the
      above mechanistic differences between the two reaction series of DMA and DMBA are
      caused by the ability of the para substituent to maintain a conjugation path
      between the C-H reaction center and the aryl moiety. Furthermore, the
      computational results show a new feature of reactivity, namely, that the N
      demethylation of DMBA proceeds by a spin-selective reaction via the high spin
      state of the active species of the enzyme. This conclusion is reinforced by the
      match of the calculated and experimental KIE values.

PMID- 20146529
TI  - Chemical constituents from the leaves and stems of Schisandra rubriflora.
AB  - Six new nortriterpenoids, schirubridilactones A-F (1-6), as well as 14 known
      compounds, were isolated from the leaves and stems of Schisandra rubriflora. The
      structures of 1-6 were elucidated on the basis of spectroscopic methods including
      HSQC, HMBC, (1)H-(1)H COSY, and ROESY NMR experiments. The relative
      stereochemistry of 1 was confirmed through single-crystal X-ray analysis. In
      addition, compounds 1-6 showed anti-HIV-1 activity with EC(50) values in the
      range 14.3-80.8 microg/mL and selectivity indices in the range 2.2-9.0.

PMID- 20146530
TI  - Tight hydrophobic contacts with the SecB chaperone prevent folding of substrate
      proteins.
AB  - The molecular chaperone SecB binds to hydrophobic sections of unfolded secretory
      proteins and thereby prevents their premature folding prior to secretion by the
      translocase of Escherichia coli. Here, we have investigated the effect of the
      single-residue mutation of leucine 42 to arginine (L42R) centrally positioned in
      the polypeptide binding pocket of SecB on its chaperonin function. The mutant
      retains its tetrameric structure and SecA targeting function but is defective in
      its holdase activity. Isothermal titration calorimetry and single-molecule
      optical tweezer studies suggest that the SecB(L42R) mutant exhibits a reduced
      polypeptide binding affinity allowing for partial folding of the bound
      polypeptide chain rendering it translocation-incompetent.

PMID- 20146531
TI  - Insights into the conformational dynamics of the E3 ubiquitin ligase CHIP in
      complex with chaperones and E2 enzymes.
AB  - The dimeric E3 ubiquitin ligase CHIP binds with its tetratricopeptide repeat
      (TPR) domain the C-terminus of molecular chaperones Hsp70 and Hsp90 and with its
      U-box region E2 ubiquitin-conjugating enzymes. By ubiquitinating chaperone-bound
      polypeptides, CHIP thus links the chaperone machinery to the proteasomal
      degradation pathway. The molecular mechanism of how CHIP discriminates between
      folding and destruction of chaperone substrates is not yet understood. Two
      recently published crystal structures of mouse and zebrafish CHIP truncation
      constructs differ substantially, showing either an asymmetric assembly or a
      symmetric assembly with a highly ordered middle domain. To characterize the
      conformational properties of the intact full-length protein in solution, we
      performed amide hydrogen exchange mass spectrometry (HX-MS) with human CHIP. In
      addition, we monitored conformational changes in CHIP upon binding of Hsp70,
      Hsp90, and their respective C-terminal EEVD peptides, and in complex with the
      different E2 ubiquitin-conjugating enzymes UbcH5a and Ubc13. Solution HX-MS data
      suggest a symmetric dimer assembly with highly flexible parts in the middle
      domain contrasting both the asymmetric and the symmetric crystal structure. CHIP
      exhibited an extraordinary flexibility with a largely unprotected N-terminal TPR
      domain. Formation of a complex with intact Hsp70 and Hsp90 or their respective C
      terminal octapeptides induced folding of the TPR domain to a defined, highly
      stabilized structure with protected amide hydrogens. Interaction of CHIP with two
      different E2 ubiquitin-conjugating enzymes, UbcH5a and Ubc13, had distinct
      effects on the conformational dynamics of CHIP, suggesting different roles of the
      CHIP-E2 interaction in the ubiquitination of substrates and interaction with
      chaperones.

PMID- 20146532
TI  - Analysis of the ontogenetic variation in the venom proteome/peptidome of Bothrops
      jararaca reveals different strategies to deal with prey.
AB  - Previous studies have demonstrated that the pharmacological activities displayed
      by Bothrops jararaca venom undergo a significant ontogenetic shift. Variation in
      the venom proteome is a well-documented phenomenon; however, variation in the
      venom peptidome is poorly understood. We report a comparative proteomic and
      peptidomic analysis of venoms from newborn and adult specimens of B. jararaca and
      correlate it with the evaluation of important venom features. We demonstrate that
      newborn and adult venoms have similar hemorrhagic activities, while the adult
      venom has a slightly higher lethal activity in mice; however, the newborn venom
      is extremely more potent to kill chicks. The coagulant activity of newborn venom
      upon human plasma is 10 times higher than that of adult venom. These differences
      were clearly reflected in their different profiles of SDS-PAGE, gelatin
      zimography, immunostaining using specific antibodies, glycosylation pattern, and
      concanavalin A-binding proteins. Furthermore, we report for the first time the
      analysis of the peptide fraction of newborn and adult venoms by MALDI-TOF mass
      spectrometry and LC-MS/MS, which revealed different contents of peptides, while
      the bradykinin potentiating peptides (BPPs) showed rather similar profiles and
      were detected in the venoms showing their canonical sequences and also novel
      sequences corresponding to BPPs processed from their precursor protein at sites
      so far not described. As a result of these studies, we demonstrated that the
      ontogenetic shift in diet, from ectothermic prey in early life to endothermic
      prey in adulthood, and in animal size are associated with changes in the venom
      proteome in B. jararaca species.

PMID- 20146533
TI  - Photochemistry of far red responsive tetrahydroquinoxaline-based squaraine dyes.
AB  - The photochemical and redox properties of two newly synthesized
      tetrahydroquinoxaline-based squaraine dyes (SQ) are investigated using femto- and
      nanosecond laser flash photolysis, pulse radiolysis, and cyclic voltammetry. In
      acetonitrile and dichloromethane, these squaraines exist as monomers in the
      zwitterionic form (lambda(max) approximately 715 nm, epsilon(max) approximately
      1.66 x 10(5) M(-1) cm(-1) in acetonitrile). Their excited singlet states ((1)SQ*)
      exhibit a broad absorption band at 480 nm, with singlet lifetimes of 44 and 123
      ps for the two dyes. Both squaraines exhibit poor intersystem crossing efficiency
      (Phi(ISC) < 0.001). Their excited triplet states ((3)SQ*), however, are
      efficiently generated by triplet-triplet energy transfer using triplet excited
      9,10-dibromoanthracene. The excited triplet states of the squaraine dyes exhibit
      a broad absorption band at ca. 560 nm (epsilon(triplet) approximately 4.2 x 10(4)
      M(-1) cm(-1)) and undergo deactivation via triplet-triplet annihilation and
      ground-state quenching processes. The oxidized forms of the investigated
      squaraines (SQ(*+)) exhibit absorption maxima at 510 and 610 nm.

PMID- 20146534
TI  - Photochemistry of 1-nitronaphthalene: a potential source of singlet oxygen and
      radical species in atmospheric waters.
AB  - 1-Nitronaphthalene (1NN) was used as a model of nitro-PAHs to investigate
      photosensitized reactions in aqueous solution in the presence of oxygen and
      halides. Laser flash photolysis (LFP) was employed to investigate electron
      transfer between halide anions and the triplet state of 1NN, leading to the
      formation of dihalogen radical anions (X(2)(*-)) in solution. The experiments
      were performed in the absence or presence of oxygen, showing a bimolecular
      quenching rate constant for the triplet state of 1NN ((3)1NN) by oxygen of (1.95
      +/- 0.05) x 10(9) M(-1) s(-1). The decay of (3)1NN was observed to strongly
      depend on the pH of the medium. At pH > 2, (3)1NN decayed with a pseudofirst
      order rate constant close to 6.0 x 10(5) s(-1). The rate constant was markedly
      enhanced at lower pHs, reaching 2.0 x 10(6) s(-1) at pH approximately 0.1, which
      suggests formation of the protonated triplet state ((3)1NNH(+)) at low pHs.
      Furthermore, we showed that the photoreactions of (3)1NN in the presence of
      oxygen are potential sources of HO(2)(*), (1)O(2), and possibly (*)OH in aqueous
      media. In Milli-Q water (pH approximately 6.5) and in the presence of halide
      anions, the quenching rate constant of (3)1NN was evaluated to be (2.9 +/- 0.4) x
      10(4) M(-1) s(-1) for chloride, (7.5 +/- 0.2) x 10(8) M(-1) s(-1) for bromide,
      and (1.1 +/- 0.1) x 10(10) M(-1) s(-1) for iodide. Also in this case a pH
      dependent reactivity was evidenced, and the quenching rate constant was (7.7 +/-
      1.2) x 10(5) M(-1) s(-1) with chloride at pH 1.1.

PMID- 20146536
TI  - Orientational imaging of single molecules by using azimuthal and radial
      polarizations.
AB  - Three-dimensional molecular orientations of single fluorescence molecules in
      polymeric thin films were measured by focused azimuthally and radially polarized
      light, in which we found that the fluorescence intensity was dependent on the
      depth position of the molecule with respect to the film surface. We found that
      the fluorescence intensity for a molecule which is 80 nm deep in the film excited
      by radial polarization is appreciably larger when compared with the fluorescence
      intensity for a molecule which is also excited by radial polarization but which
      is closer to the polymer/air interface, a feature which leads to different
      fluorescence intensities, under excitation by radial polarization, for molecules
      with the same polar orientation but with different depths inside the film. We
      also found that the variation of fluorescence intensity from a molecule inside an
      80 nm film in radial polarization is appreciably larger compared with one in
      azimuthal polarization. These findings were confirmed by comparing experiments
      using different thickness films with theoretically calculated electric field
      distributions.

PMID- 20146535
TI  - Kinetic mechanistic studies of wild-type leucine-rich repeat kinase 2:
      characterization of the kinase and GTPase activities.
AB  - Recent studies have identified mutations in the leucine-rich repeat kinase2 gene
      (LRRK2) in the most common familial forms and some sporadic forms of Parkinson's
      disease (PD). LRRK2 is a large and complex protein that possesses kinase and
      GTPase activities. Some LRRK2 mutants enhance kinase activity and possibly
      contribute to PD through a toxic gain-of-function mechanism. Given the role of
      LRRK2 in the pathogenesis of PD, understanding the kinetic mechanism of its two
      enzymatic properties is critical for the discovery of inhibitors of LRRK2 kinase
      that would be therapeutically useful in treating PD. In this report, by using
      LRRK2 protein purified from murine brain, first we characterize kinetic
      mechanisms for the LRRK2-catalyzed phosphorylation of two peptide substrates: PLK
      derived peptide (PLK-peptide) and LRRKtide. We found that LRRK2 follows a rapid
      equilibrium random mechanism for the phosphorylation of PLK-peptide with either
      ATP or PLK-peptide being the first substrate binding to the enzyme, as evidenced
      by initial velocity and inhibition mechanism studies with nucleotide analogues
      AMP and AMP-PNP, product ADP, and an analogue of the peptide substrate. The
      binding of the first substrate has no effect on the binding affinity of the
      second substrate. Identical mechanistic conclusions were drawn when LRRKtide was
      the phosphoryl acceptor. Next, we characterize the GTPase activity of LRRK2 with
      a k(cat) of 0.2 +/- 0.02 s(-1) and a K(m) of 210 +/- 29 microM. A SKIE of 0.97 +/
      0.04 was measured on k(cat) for the GTPase activity of LRRK2 in a D(2)O molar
      fraction of 0.86 and suggested that the product dissociation step is rate
      limiting, of the steps governed by k(cat) in the LRRK2-catalyzed GTP hydrolysis.
      Surprisingly, binding of GTP, GDP, or GMP has no effect on kinase activity,
      although GMP and GDP inhibit the GTPase activity. Finally, we have identified
      compound LDN-73794 through screen of LRRK2 kinase inhibitors. Our study revealed
      that this compound is a competitive inhibitor of the binding of ATP and inhibits
      the kinase activity without affecting the GTPase activity.

PMID- 20146537
TI  - Glass matrix-facilitated thermal reduction: a tool for probing reactions of met
      hemoglobin with nitrite and nitric oxide.
AB  - Isolating elemental steps that comprise a protein reaction in solution is a
      difficult process. In this study, the use of sugar-derived glass matrices is
      evaluated as a biophysical tool to help dissect out elemental steps and isolate
      intermediates. Two features of the glass are utilized in this endeavor: (i) the
      capacity of trehalose glass matrices to support thermal reduction over
      macroscopic distances; and (ii) the ability of glass matrices to significantly
      damp large amplitude protein dynamics. The focus of the study is on the reaction
      of nitric oxide (NO) with a nitrite ion coordinated to the heme iron of
      hemoglobin (Hb). The thermal reduction property of the glass is used to generate
      NO from nitrite within the glass, and the damping of protein dynamics is used to
      control entry of NO into the distal heme pocket of Hb, where it can either
      interact with bound nitrite or bind to the heme iron. The results not only relate
      to earlier controversial studies addressing the reactions of Hb with NO and
      nitrite but also raise the prospect that these properties of sugar-derived glassy
      matrices can be exploited as a new biophysical tool to modulate and probe
      reactions of NO with hemeproteins as well as a wide range of other
      metalloproteins.

PMID- 20146538
TI  - Series of M(I)[Co(bpy)3][Mo(CN)8] x nH2O (M(I) = Li (1), K (2), Rb (3), Cs (4); n
      = 7-8) exhibiting reversible diamagnetic to paramagnetic transition coupled with
      dehydration-rehydration process.
AB  - In this paper we report the synthesis and the structural and magnetic properties
      of the series of ionic compounds with general formula:
      M(I)[Co(bpy)(3)][Mo(CN)(8)] x nH(2)O (M(I) = Li, n = 8 (1), M(I) = K, n = 8 (2),
      M(I) = Rb, n = 8 (3), M(I) = Cs, n = 7.5 (4)). Solids 1-4 are characterized by
      the optical outer-sphere metal-to-metal charge transfer (MMCT) transition from
      Mo(IV) center to Co(III) center in the visible region and the Co(III)Mo(IV) <==>
      Co(II)Mo(V) spin equilibrium strongly dominated by the Co(III)Mo(IV) form. We
      show a gentle thermal treatment of diamagnetic compounds 1-4 leading to the
      dehydrated forms 1a-4a, which reveal a significant increase of paramagnetic
      contribution (from 0.5 to 2% to 30-40%). The rehydration allows to recover the
      diamagnetic phases 1b-4b of compositions and properties similar to those of 1-4.
      The irradiation of the dehydrated form 2a within the MMCT band in the
      Superconducting Quantum Interference Device (SQUID) cavity at T = 10 K causes
      further increase of the Co(II)Mo(V) contribution giving the metastable phase
      annealed back to the 2a phase after heating above T = 290 K. The IR, electron
      paramagnetic resonance (EPR), and X-ray photoelectron spectroscopy (XPS)
      spectroscopic data along with the magnetic data are interpreted in terms of
      strong modification of the Co(III)Mo(IV) <==> Co(II)Mo(V) equilibrium occurring
      in these systems.

PMID- 20146539
TI  - What determines the miscibility of ionic liquids with water? Identification of
      the underlying factors to enable a straightforward prediction.
AB  - Whether an ionic liquid (IL) is water-miscible or immiscible depends on the
      particular ions that constitute it. We propose an explanation, based on molecular
      simulations, how ions determine the miscibility of ILs and suggest a
      straightforward and computationally inexpensive method to predict the miscibility
      of arbitrary new ILs. The influence of ions on the solvation of water is analyzed
      by comparing molecular dynamics simulations of water in 9 different ILs with
      varying cation and anion constituents. The solvation of water in ILs is found to
      depend primarily on the electrostatic water-ion interaction strength, which, in
      turn, is determined mainly by two factors: primarily, by the size of the ions and
      secondarily by the amount of charge on the ion surface that is coordinated with
      water. It is demonstrated that large ions lead to weaker interactions with water,
      due to the involved delocalization of the ion charge. A large charge on the ion
      surface, which is determined by the chemical structure of the ion, strengthens
      water-ion interactions. We observe that whenever the interaction strength of
      water with ions exceeds a certain threshold, an IL becomes water-miscible. On the
      basis of these findings, a simple equation is derived that estimates the water
      ion interaction strength. With this equation it is possible to predict most of
      the observed water-miscibilities of a sample of 83 ILs correctly. A linear
      increase of the water saturation concentration with the estimated water-ion
      interaction strength is observed in water-immiscible ILs, which can be utilized
      to predict the water concentration in new ILs.

PMID- 20146540
TI  - Ability to adapt: different generations of PAMAM dendrimers show different
      behaviors in binding siRNA.
AB  - This paper reports a molecular dynamic study to explore the diverse behavior of
      different generations of poly(amidoamine) (PAMAM) dendrimers in binding siRNA.
      Our models show good accordance with experimental measurements. Simulations
      demonstrate that the molecular flexibility of PAMAMs plays a crucial role in the
      binding event, which is controlled by the modulation between enthalpy and entropy
      of binding. Importantly, the ability of dendrimers to adapt to siRNA is strongly
      dependent on the generation and on the pH due to backfolding. While G4
      demonstrates good adaptability to siRNA, G6 behaves like a rigid sphere with a
      consistent loss in the binding affinity. G5 shows a hybrid behavior, maintaining
      rigid and flexible aspects, with a strong dependence of its properties on the pH.
      To define the "best binder", the mere energetic definition of binding affinity
      appears to be no longer effective and a novel concept of "efficiency" should be
      considered, being the balance between enthalpy and entropy of binding indivisible
      from the structural flexibility. With this aim, we propose an original criterion
      to define and rank the ability of these molecules to adapt their structure to
      bind a charged target.

PMID- 20146541
TI  - Synthesis, spectral, structural, second-order nonlinear optical properties and
      theoretical studies on new organometallic donor-acceptor substituted nickel(II)
      and copper(II) unsymmetrical Schiff-base complexes.
AB  - The synthesis, spectroscopic and structural characterization, linear and
      nonlinear optical properties, as well as the electrochemical behavior of a series
      of robust neutral binuclear M[Fc-C(O)CH=C(CH(3))N-X-N=CH-(2-O,5-R-C(6)H(3))] (M =
      Ni (4), Cu (5), X = o-C(6)H(4), R = H; M = Ni (9), X = CH(2)CH(2), R = OH), and
      their corresponding ionic trinuclear [M{Fc-C(O)CH=C(CH(3))N-X-N=CH-(eta(6)-2-O,5
      R-C(6)H(3))RuCp*}][PF(6)] (6, 7, 10), M[ONNO]-type unsymmetrical Salophen and
      salen complexes featuring ferrocenyl (Fc) donor and the mixed sandwich acceptor
      [Cp*Ru(eta(6)- salicylidene)](+) as a push-pull moiety are reported in this paper
      (Fc = CpFe(eta(5)-C(5)H(4)); Cp = eta(5)-C(5)H(5); Cp* = eta(5)-C(5)Me(5)). The
      single-crystal X-ray structure of the bimetallic iron-nickel derivative 4
      indicates a bowed structure of the unsymmetrical Schiff base skeleton. The Ni(II)
      ion is tetracoordinated in a square planar environment, with two nitrogen atoms
      and two oxygen atoms as donors. The new metalloligand [Fc
      C(O)CH=C(CH(3))N(H)CH(2)CH(2)N=CH-(2,5-(OH)(2)C(6)H(3))] (8) obtained from the
      Schiff base condensation of 2,5-dihydroxobenzaldehyde with the half-unit
      precursor, Fc-C(O)CH=C(CH(3))N(H)CH(2)CH(2)NH(2) (2), is reported with its
      crystal structure showing partial delocalization of the heteroconjugated [O-C-C-C
      N] frameworks with a dihedral angle between the respective planes of 60.76
      degrees. Second order nonlinear optical (NLO) measurements were achieved using
      the Harmonic Light Scattering technique to probe the role of the M[ONNO]
      chromophores and of the pi-complexation of the salicylidene ring in the
      nonlinearity. All the complexes exhibit a second-order nonlinear response
      increasing with the nuclearity, the hyperpolarizability (beta) value of the
      trinuclear complex 10 being 1.5 time larger than that of the metalloligand 8
      (beta = 155 x 10(-30) esu). A rationalization of the structural, electronic, and
      redox properties of the title compounds is provided, based on a theoretical
      investigation at the density functional theory (DFT) level. Their UV-visible
      spectra has been assigned with the help of time-dependent (TD) DFT calculations.
      They are dominated by LMCT, MLCT, and pi-pi* transitions.

PMID- 20146542
TI  - Classical separation.

PMID- 20146543
TI  - Unfolding of hydrophobic polymers in guanidinium chloride solutions.
AB  - Guanidinium chloride (GdmCl) is a widely used chemical denaturant that unfolds
      proteins. Its effects on hydrophobic interactions are, however, not fully
      understood. We quantify the effects of GdmCl on various manifestations of
      hydrophobicity--from solvation and interactions of small solutes to folding
      unfolding of hydrophobic polymers--in water and in concentrated GdmCl solutions.
      For comparison, we also perform similar calculations in solutions of NaCl and
      CsCl in water. Like NaCl and CsCl, GdmCl increases the surface tension of water,
      decreases the solubility of small hydrophobic solutes, and enhances the strength
      of hydrophobic interactions at the pair level. However, unlike NaCl and CsCl,
      GdmCl destabilizes folded states of hydrophobic polymers. We show that Gdm(+)
      ions preferentially coat the hydrophobic polymer, and it is the direct van der
      Waals interaction between Gdm(+) ions and the polymer that contributes to the
      destabilization of folded states. Interestingly, the temperature dependence of
      the free energy of unfolding of the hydrophobic polymer in water is protein-like,
      with signatures of both heat and cold denaturation. Addition of GdmCl shifts the
      cold denaturation temperature higher, into the experimentally accessible region.
      Finally, translational as well as conformational dynamics of the polymer are
      slower in GdmCl and correlate with dynamics of water molecules in solution.

PMID- 20146544
TI  - Enrichment of O-GlcNAc modified proteins by the periodate oxidation-hydrazide
      resin capture approach.
AB  - A chemical derivatization approach has been developed for the enrichment of O
      GlcNAc modified proteins. The procedure is based on the isolation technique used
      for N-glycoproteins with appropriate modifications because of the differences in
      the two types of glycosylation: a prolonged periodate oxidation is followed by
      hydrazide resin capture, on-resin proteolytic digestion, and release of the
      modified peptides by hydroxylamine. This enrichment strategy offers a fringe
      benefit in mass spectrometry analysis. Upon collisional activation, the presence
      of the open carbohydrate ring leads to characteristic fragmentation facilitating
      both glycopeptide identification and site assignment. The enrichment protocol was
      applied to the Drosophila proteasome complex previously described as O-GlcNAc
      modified. The O-GlcNAc modification was located on proteasome interacting
      proteins, deubiquitinating enzyme Faf (CG1945) and a ubiquitin-like domain
      containing protein (CG7546). Three other proteins were also found GlcNAc
      modified, a HSP70 homologue (CG2918), scribbled (CG5462) and the 205 kDa
      microtubule-associated protein (CG1483). Interestingly, in the HSP70 homologue
      the GlcNAc modification is attached to an asparagine residue of a N-glycosylation
      motif.

PMID- 20146547
TI  - Strategies for improving asthma outcomes: a case-based review of successes and
      pitfalls.
AB  - Several comprehensive community-based asthma management programs have been
      developed in recent years. Their central goal is to provide access to quality
      asthma care to achieve successful long-term disease management. The Kansas City
      Children's Asthma Management Program (KC CAMP) and the Asthma Network of West
      Michigan (ANWM) share many of the same objectives, which include educating
      patients, families, the community, and health care providers about asthma care,
      advocating on behalf of those who need care, and allocating resources to provide
      care. Education to promote behavioral changes in health care providers enrolled
      in KC CAMP was achieved through didactic sessions and was considered successful;
      provider and staff satisfaction increased, as did compliance with treatment
      guidelines. ANWM seeks to promote prevention rather than crisis care by providing
      home visits, physician care conferences to generate asthma management plans, and
      social workers to address psychosocial barriers to care. Funding from multiple
      resources is essential for maintaining the programs. In addition, staff work with
      corporate sponsors, governmental agencies, and individual donors to ensure the
      programs' success. The benefits of KC-CAMP and ANWM are evident with data showing
      dramatic declines in emergency department visits, hospitalizations, and overall
      health care costs for asthma care.

PMID- 20146545
TI  - Antigen identification and characterization of lung cancer specific monoclonal
      antibodies produced by mAb proteomics.
AB  - A mass spectrometric (MS)-based strategy for antigen (Ag) identification and
      characterization of globally produced monoclonal antibodies (mAbs) is described.
      Mice were immunized with a mixture of native glycoproteins, isolated from the
      pooled plasma of patients with nonsmall cell lung cancer (NSCLC), to generate a
      library of IgG-secreting hybridomas. Prior to immunization, the pooled NSCLC
      plasma was subjected to 3-sequential steps of affinity fractionation, including
      high abundant plasma protein depletion, glycoprotein enrichment, and polyclonal
      antibody affinity chromatography normalization. In this paper, to demonstrate the
      high quality of the globally produced mAbs, we selected 3 mAbs of high
      differentiating power against a matched, pooled normal plasma sample. After
      production of large quantities of the mAbs from ascites fluids, Ag identification
      was achieved by immunoaffinity purification, SDS-PAGE, Western blotting, and MS
      analysis of in-gel digest products. One antigen was found to be complement factor
      H, and the other two were mapped to different subunits of haptoglobin (Hpt). The
      2 Hpt mAbs were characterized in detail to assess the quality of the mAbs
      produced by the global strategy. The affinity of one of the mAbs to the Hpt
      native tetramer form was found to have a K(D) of roughly 10(-9) M and to be 2
      orders of magnitude lower than the reduced form, demonstrating the power of the
      mAb proteomics technology in generating mAbs to the natural form of the proteins
      in blood. The binding of this mAb to the beta-chain of haptoglobin was also
      dependent on glycosylation on this chain. The characterization of mAbs in this
      work reveals that the global mAb proteomics process can generate high-quality
      lung cancer specific mAbs capable of recognizing proteins in their native state.

PMID- 20146548
TI  - Introduction: landscape of opioid dependence.
AB  - BACKGROUND: The use of opioids for chronic noncancer pain increased 222% from
      1992 to 2002. Opioid dependence has also increased significantly, leading to a
      burden on patients, employers, insurers, society, and the entire health care
      system. It is imperative that opioid dependence is addressed and treated
      properly, in order to return patients to being productive participants in the
      workplace and society. OBJECTIVE: To provide an overview of addiction, abuse, and
      dependence and identify risk factors for addiction. SUMMARY: Studies have shown
      that intensive use of opioids is associated with increased utilization of costly
      health care services, prolonged disability, and continued use of opioids, leading
      to abuse and dependence in many patients. While identifying patients at risk for
      developing opioid dependence is difficult, there are many risk stratification
      tools now available to practitioners, including the Opioid Risk Tool (ORT) or
      Screener and Opioid Assessment for Patients with Pain (SOAPP). Understanding the
      differences between dependence, addiction, and tolerance is essential to managing
      patients on opioids. CONCLUSION: It is imperative that patients be properly
      managed when being treated for pain. Physicians and employers have to be able to
      identify patients at risk for opioid abuse or exhibiting symptoms of opioid abuse
      and know how to address their needs.

PMID- 20146549
TI  - Empirical view of opioid dependence.
AB  - BACKGROUND: The impact of opioid dependence on employers, managed care, and
      society is significant. Inappropriate use of narcotic analgesics leads to
      uncontrolled pain management, dependence, and may lead to patient deaths,
      creating a tremendous cost burden to the health care system. OBJECTIVE: To
      provide an overview of the clinical and economic impact of treating opioid
      dependence on managed care, employers, and society. SUMMARY: An estimated 6% to
      15% of people in the United States abuse drugs, and approximately 20% of
      Americans report using prescription opioids for nonmedical use. This is
      associated with an annual cost of nearly half a trillion dollars, taking into
      account the medical, economic, social, and criminal impact of this abuse. A
      recent study showed that patients who abuse opioids generate mean annual direct
      health care costs 8.7 times higher than nonabusers. The National Survey on Drug
      Use and Health (NSDUH), conducted by the Substance Abuse and Mental Health
      Services Administration (SAM HSA), found that patients who report opioid abuse
      miss more than 2.2 days of work monthly, compared with the 0.83 days per month
      reported for the average person. Presenteeism and productivity are also affected
      by misuse and dependence on opioids. CONCLUSION: The costs associated with opioid
      dependence are significant. Physicians, employers, and managed care organizations
      must be proactive in appropriately diagnosing and treating patients who suffer
      from substance abuse disorders in order to lessen this economic burden.

PMID- 20146550
TI  - Opioid dependence treatment and guidelines.
AB  - BACKGROUND: In response to the growing incidence of opioid dependence, guidelines
      have been created, and new treatments are being developed to assist physicians in
      treating dependence and withdrawal of opioids. OBJECTIVE: To review treatment
      modalities and guidelines utilized in opioid dependence. SUMMARY: Guidelines for
      the treatment of opioid dependence have been developed by organizations such as
      the American Society of Interventional Pain Physicians (ASIPP) and the American
      Psychiatric Association (APA). Current guidelines recommend comprehensive
      treatment with pharmacological agents such as methadone, buprenorphine, or
      buprenorphine combined with naloxone as well as psychosocial therapy. These
      guidelines stress the need for an integrated approach to treatment. Office-based
      opioid treatment is currently being utilized to treat opioid dependent patients
      in a physician's office setting with buprenorphine/naloxone replacement therapy
      as an alternative to entering patients into a methadone clinic. These office
      based programs offer a breakthrough in access to care for dependent patients.
      CONCLUSION: Physicians need to be aware of and adhere to currently accepted
      guidelines and recommendations for treating opioid dependent patients, including
      integrating psychosocial treatments and behavior modification strategies for
      optimal results. Clinicians must be educated on the new treatment modalities and
      regulations surrounding the use of these therapies.

PMID- 20146551
TI  - Patient perspective, complexities, and challenges in managed care.
AB  - BACKGROUND: Lack of coordination of care is one of the largest obstacles involved
      with treating opioid dependence. Physicians also face the challenges of managing
      comorbidities and dealing with relapse. OBJECTIVE: To examine the clinical,
      economic, and humanistic factors involved in treating opioid dependence. SUMMARY:
      Despite the extensive utilization of narcotic analgesics, pain is often
      uncontrolled. Effective pain management and coordination of care is essential in
      treating pain patients, as patients who abuse pain medications consume more
      health care resources than nonabusers. Patients who abuse are 2.3 times more
      likely to present at the emergency department and 6.7 times more likely to be
      hospitalized than nonabusers. Managed care organizations are now incorporating
      integrated approaches to treating pain and substance abuse disorders, realizing
      that patients must be looked at as a whole, considering alternative and
      behavioral therapies in addition to pharmacological treatments. They are also
      able to assess patterns of abuse using pharmacy claims data and alert physicians
      to potential problems by making use of prescription monitoring programs.
      Physicians who treat chronic pain must utilize strategies to minimize the risk of
      developing dependence on opioids, and practitioners treating opioid dependence
      must employ policies to optimize outcomes. Such strategies include developing
      pain contracts; performing random urine screenings and pill counts; and setting
      goals of therapy and re-evaluating patients throughout treatment. Plans must be
      in place in the event of relapse, as well. CONCLUSION: In order to be successful
      in managing opioid dependence, physicians, employers, and managed care
      organizations must work together to provide an integrated approach to treatment.

PMID- 20146552
TI  - Practice strategies to improve compliance and patient self-management.
AB  - BACKGROUND: Failure in treating opioid dependence is costly to the patient, the
      employer, managed care organizations, and the overall health care system. Opioid
      dependent patients tend to be less productive at work and in society and utilize
      a great many health care resources. Optimizing outcomes is essential. OBJECTIVE:
      To introduce the benefit of integrated strategies and patient support in the
      treatment of opioid dependence. SUMMARY: Health Analytics is currently studying
      the benefit of HereToHelp, a behavioral support program in which registered
      nurses or addiction treatment counselors with specialized training in addiction
      education provide information and encouragement to patients receiving
      pharmacologic treatment for opioid dependence. A total of 470 physicians in 41
      states have been enlisted to participate in this patient support study. The study
      hypothesis is that patients who receive behavioral support and encouragement will
      be more compliant with their opioid replacement therapy, leading to better
      outcomes. Additional treatment strategies are also being developed to minimize
      the risk of abuse and diversion. Prodrugs and vaccines are also being
      investigated. CONCLUSION: A coordinated team approach is essential in treating
      pain patients and opioid-dependent patients. Offering behavior modification in
      addition to pharmacotherapy and utilizing strategies such as prescription
      monitoring programs, pain contracts, and screening are all vital components
      necessary for positive outcomes.

PMID- 20146553
TI  - Investigating effect of microemulsion components: In vitro permeation of
      ketoconazole.
AB  - The purpose of this study was to evaluate the effect of oil, surfactant/co
      surfactant mixing ratios and water on the in vitro permeation of ketoconazole
      (KTZ) applied in O/W microemulsion vehicle through intact rat skin. Lauryl
      Alcohol (LA) was screened as the oil phase of microemulsions, due to a good
      solubilizing capacity of the microemulsion system. The pseudo-ternary phase
      diagrams for microemulsion regions were constructed using LA as the oil, Labrasol
      (Lab) as the surfactant (S) and ethanol (EtOH) as the cosurfactant (CoS). The
      formulation which showed a highest permeation rate of 54.65 +/- 1.72
      ug/cm(2)/h(1) and appropriate physico-chemical properties was optimized as
      containing 2% KTZ, 10% LA, 20% Lab/EtOH (1:1) and 68% double distilled water
      (w/w). The efficiency of microemulsion formulation in the topical delivery of KTZ
      was dependent upon the contents of water and LA as well as Lab/EtOH mixing ratio.
      It was concluded that the percutaneous absorption of KTZ from microemulsions was
      enhanced with increasing the LA and water contents, and with decreasing the
      Lab/EtOH ratio in the formulation. Candida albicans was used as a model fungus to
      evaluate the antifungal activity of the best formula achieved, which showed the
      widest zone of inhibition as compared to KTZ reference. The studied microemulsion
      formulation showed a good stability for a period of three months.
      Histopathological investigation of rat skin revealed the safety of microemulsion
      formulations for topical use. These results indicate that the studied
      microemulsion formulation might be a promising vehicle for topical delivery of
      KTZ.

PMID- 20146554
TI  - Regulation of intracellular pH by Ca2+-activated proton channel.
AB  - BACKGROUND AND AIM: We have characterized a membrane current associated with a
      decrease in pHi, which can be induced by either elevating intracellular calcium
      or extracellular application of methylmercury (a potent agent in elevating
      intracellular Ca(2+) concentration) in the alveolar macrophages bathing in the
      impermeant bilateral cesium aspartate solution. RESULTS: Decreasing pHi and
      elevating [Ca(2+)]i profoundly enhanced, but H-7 (a broad-spectrum kinase
      inhibitor), W-7 (a selective calmodulin antagonist) and KN-93 (a calmodulin
      kinase II inhibitor) inhibited the currents. CONCLUSION: These results indicate
      that rat alveolar macrophages possess a calcium-activated and pHi-sensitive
      proton channel which can be phosphorylated and activated by calmodulin kinase II.

PMID- 20146555
TI  - Methodology of systematic reviews and recommendations.
AB  - Although research in the field of spinal cord injury (SCI) is a relatively new
      endeavor, a remarkable number of papers focused on this subspecialty have been
      published in a broad variety of journals over the last two decades. A
      multidisciplinary group of experts, including clinical epidemiologists,
      neurosurgical and orthopedic spine surgeons, basic scientists, rehabilitation
      specialists, intensivists, and allied health professionals (nursing and physical
      therapy) was assembled through the Spinal Cord Injury Solutions Network to
      summarize the existing literature focusing on 12 key topics related to acute
      traumatic SCI, which have not been recently reviewed. The objective was to
      develop evidence-based recommendations to help translate current science into
      clinical practice and to identify new directions for research. For each topic one
      to three specific questions were formulated by consensus through the expert
      panel. A systematic review of the literature was performed to determine the
      current evidence for the specific questions. A primary literature search was
      performed using MEDLINE, CINAHL, EMBASE, and Cochrane databases. A secondary
      search strategy incorporated additional articles referenced in significant
      publications (i.e., meta-analysis, systematic and nonsystematic review articles).
      Two reviewers independently reviewed the titles and abstracts yielded by this
      comprehensive search and subsequently selected articles based on the
      predetermined inclusion and inclusion criteria. Data were extracted for
      population into evidentiary tables. Selected articles were rated for level of
      evidence and methodological quality, information that was also included in
      evidentiary tables. Disagreements were resolved by a third reviewer or consensus
      based discussion. Based on the evidence compiled, answers to the targeted
      questions were formulated and recommendations generated by consensus-based
      discussion and anonymized voting using Delphi methodology. A level of consensus
      of 80% or higher was considered to represent strong agreement.

PMID- 20146556
TI  - Pharmacokinetics and disposition of CS-8958, a long-acting prodrug of the novel
      neuraminidase inhibitor laninamivir in rats.
AB  - CS-8958, a prodrug of laninamivir (R-125489), is currently under development as
      an inhaled anti-influenza drug. In this study, the pharmacokinetics and
      disposition of CS-8958 were characterized in rats. After intratracheal
      administration of 14C-CS-8958, radioactivity was retained over long periods in
      the target tissues (trachea and lung) as its active metabolite R-125489 - 19.12%
      of the dose was retained in the lung at 24 h. After intratracheal administration
      of CS-8958, plasma R-125489 concentration was slowly eliminated, and its half
      life (14.1 h) was considerably longer than that after intravenous administration
      of R-125489. The radioactivity of intratracheally administered 14C-CS-8958 was
      mainly excreted into the urine (67.5% of dose), and this excretion lasted over
      long periods. R-125489 accounted for most of the urinary radioactivity recovered
      after 24 h. These results demonstrated that CS-8958 administered intratracheally
      to rats was converted/hydrolysed to R-125489 in the target tissues, and that the
      R-125489 was slowly excreted into the urine via an absorption rate-limiting
      process. Such distinctive pharmacokinetics attributed to the slow release of R
      125489 suggests the potential for a long-acting anti-influenza drug.

PMID- 20146557
TI  - A systematic review of cellular transplantation therapies for spinal cord injury.
AB  - Cell transplantation therapies have become a major focus in pre-clinical research
      as a promising strategy for the treatment of spinal cord injury (SCI). In this
      article, we systematically review the available pre-clinical literature on the
      most commonly used cell types in order to assess the body of evidence that may
      support their translation to human SCI patients. These cell types include Schwann
      cells, olfactory ensheathing glial cells, embryonic and adult neural
      stem/progenitor cells, fate-restricted neural/glial precursor cells, and bone
      marrow stromal cells. Studies were included for review only if they described the
      transplantation of the cell substrate into an in-vivo model of traumatic SCI,
      induced either bluntly or sharply. Using these inclusion criteria, 162 studies
      were identified and reviewed in detail, emphasizing their behavioral effects
      (although not limiting the scope of the discussion to behavioral effects alone).
      Significant differences between cells of the same "type" exist based on the
      species and age of donor, as well as culture conditions and mode of delivery.
      Many of these studies used cell transplantations in combination with other
      strategies. The systematic review makes it very apparent that cells derived from
      rodent sources have been the most extensively studied, while only 19 studies
      reported the transplantation of human cells, nine of which utilized bone-marrow
      stromal cells. Similarly, the vast majority of studies have been conducted in
      rodent models of injury, and few studies have investigated cell transplantation
      in larger mammals or primates. With respect to the timing of intervention, nearly
      all of the studies reviewed were conducted with transplantations occurring
      subacutely and acutely, while chronic treatments were rare and often failed to
      yield functional benefits.

PMID- 20146559
TI  - A poly(gamma-glutamic acid)-amphiphile complex as a novel nanovehicle for drug
      delivery system.
AB  - Recently, many studies have focused on biomedical and pharmaceutical applications
      of self-assembled nanoparticles. In addition, several biodegradable nanoparticles
      have been reported to possess poor dispersion stability and poor size
      controllability. However, these nanoparticles require complicated fabrication
      procedures using synthesis techniques. We developed an efficient method for
      producing nanoparticles derived from a biological origin of molecule poly(gamma
      glutamic acid) (gamma-PGA), a cationic lipid, and doxorubicin (Dox). The complex
      had a size of 510 nm and was able to encapsulate over 90% of the added Dox. An in
      vivo assay of antitumor activity demonstrated that the complex had significant
      antitumor activity in sarcoma 180-bearing mice, and was effectively accumulated
      in solid tumors based on the EPR effect. The data suggested that this complex is
      a promising formulation of gamma-PGA for targeted delivery to solid tumors. gamma
      PGA-12GP2 complexes may possess several unique advantages, including simplicity
      of nanoparticle preparation, high drug-carrying capacity, appropriate size to
      allow deeper penetration based on EPR effect into solid tumors, and lack of
      necessity to modify the chemical structure of the drugs. These data indicate that
      the gamma-PGA-12GP2 complexes are potentially useful in cancer chemotherapy.

PMID- 20146558
TI  - A systematic review of non-invasive pharmacologic neuroprotective treatments for
      acute spinal cord injury.
AB  - An increasing number of therapies for spinal cord injury (SCI) are emerging from
      the laboratory and seeking translation into human clinical trials. Many of these
      are administered as soon as possible after injury with the hope of attenuating
      secondary damage and maximizing the extent of spared neurologic tissue. In this
      article, we systematically review the available pre-clinical research on such
      neuroprotective therapies that are administered in a non-invasive manner for
      acute SCI. Specifically, we review treatments that have a relatively high
      potential for translation due to the fact that they are already used in human
      clinical applications, or are available in a form that could be administered to
      humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies,
      minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol,
      atorvastatin, inosine, and pioglitazone. The literature was systematically
      reviewed to examine studies in which an in-vivo animal model was utilized to
      assess the efficacy of the therapy in a traumatic SCI paradigm. Using these
      criteria, 122 studies were identified and reviewed in detail. Wide variations
      exist in the animal species, injury models, and experimental designs reported in
      the pre-clinical literature on the therapies reviewed. The review highlights the
      extent of investigation that has occurred in these specific therapies, and points
      out gaps in our knowledge that would be potentially valuable prior to human
      translation.

PMID- 20146560
TI  - Eczematous dermatitis after vascular laser therapy: a report of two cases.
AB  - Eczematous dermatitis was found in two port wine stain (PWS) lesions in two
      different individuals following variable pulsed 532-nm laser therapy. Both of the
      individuals described in this report had received low-dose superficial X-ray
      several years prior to the development of the eczematous dermatitis. The
      eczematous dermatitis in the PWS lesions was characterized by oozing, crusting,
      and pruritus, which showed a tendency to expand to other sites when exacerbated.
      Treatment with topical corticosteroid ointments produced some temporary
      improvement, but the dermatitis in both cases recurred when the topical
      medications were stopped. The mechanism of action for the development of an
      eczematous dermatitis in a PWS remains unclear, but may be related to multiple
      factors including abnormal hemodynamic forces resulting from the malformed
      vessels, an abnormal production of cytokines, local pathophysiological and
      immunological changes resulting from either the X-ray therapy or the laser
      therapy, and atopic constitution inherent in these individuals. These hypotheses
      and ideas need further study for additional insight into this rare, but reported
      adverse event.

PMID- 20146561
TI  - Generation of induced pluripotent stem cells from human adipose-derived stem
      cells without c-MYC.
AB  - Human adipose-derived stem cells (hASCs) are ubiquitous, plentiful, and
      easily/safely obtainable cells derived from adipose tissue, regardless of the age
      and sex of the donor. However, the hASCs have limited proliferative and
      differentiation capabilities. In this study, we examined whether induced
      pluripotent stem cells (iPSCs) could be generated from hASCs. We transduced hASCs
      with three human transcription factors (OCT3/4, SOX2, and KLF4), and found that
      they formed human embryonic stem cell (ESC)-like colonies. Importantly, we did
      not transduce c-MYC, which is usually utilized to generate iPSCs but is
      considered an oncogene. These colonies expressed human ESC-specific surface
      antigens (stage-specific embryonic antigens SSEA-3 and SSEA-4, and tumor-related
      antigens TRA-1-60 and TRA-1-81), endogenous transcription factors (OCT3/4, NANOG,
      and SOX2), and undifferentiated human ESC marker genes (REX1, UTF1, GDF3, DPPA2,
      DPPA4, and DPPA5). Further, the colonies were able to differentiate into the
      three germ layers both in vitro and in vivo. These results show that human iPSCs
      can be generated by the transduction of three factors (OCT3/4, SOX2, and KLF4)
      into hASCs.

PMID- 20146563
TI  - Changes in hepatic blood flow during whole body hyperthermia.
AB  - PURPOSE: Changes in blood flow distribution are important for heat dispersion and
      for supportive therapeutic strategies such as simultaneous whole body
      hyperthermia (WBH) and administration of chemotherapy. The aim of this clinical
      study was to determine changes in hepatic blood flow during WBH for the treatment
      of metastatic cancer. MATERIALS AND METHODS: This observational clinical study
      was part of a phase I/II feasibility study of WBH. WBH was induced using a
      radiant heat device. Hepatic blood flow was estimated using indocyanine green
      clearance measurements. The plasma disappearance rate of indocyanine green (PDR
      ICG) was recorded in percent/min. We used an invasive thermo-dye-dilution
      technique to estimate hepatic blood flow, cardiac output, and volume status. Mean
      arterial blood pressure was also measured invasively. To determine the effects of
      hyperthermia the measurements were performed at defined temperature points.
      RESULTS: In 10 of 22 treatments the PDR-ICG fell below normal values during
      hyperthermia, which represented a significant fall in hepatic blood flow. Cardiac
      output, volume status, and mean arterial blood pressure did not differ between
      patients whose liver blood flow was reduced and those whose liver blood flow
      remained unchanged. CONCLUSIONS: We observed distinct reductions in hepatic blood
      flow during WBH, which suggested a significant redistribution of blood flow away
      from the core during WBH. This was not mirrored by global circulatory parameters.

PMID- 20146564
TI  - Gene expression profiles of diabetic mice treated with whole body hyperthermia: A
      high-density DNA microarray analysis.
AB  - Previously we have demonstrated that whole body hyperthermia (WBH) improves
      insulin resistance in diabetic mice. The aim of the present study was to perform
      a gene expression analysis of the liver and adipose tissue of obesity-induced
      insulin resistant diabetic mice (db/db mice) after WBH and to define the
      molecules that play the important role in improvement of insulin resistance by
      WBH. Male db/db mice were treated with WBH 3 times per week for 12 weeks. Total
      RNA was extracted from the liver and adipose tissue of db/db mice, and
      differences in the gene expression profiles among db/+ mice, untreated db/db
      mice, and WBH-treated db/db mice were investigated using a high-density DNA
      microarray. WBH directly targets liver and adipose tissue, resulting in
      modifications in NF-kappaB and IL-6 signalling pathways, as well as lipid
      metabolism. Although the mechanisms have not yet been completely investigated, we
      can conclude that WBH may provide a new therapeutic or preventive modality
      against type 2 diabetes mellitus and metabolic or insulin resistance syndrome
      through the modification of several signalling pathways.

PMID- 20146565
TI  - Regional hyperthermia added to intensified preoperative chemo-radiation in
      locally advanced adenocarcinoma of middle and lower rectum.
AB  - PURPOSE: To evaluate the safety of delivering pre-operative regional hyperthermia
      (HT) plus an intensified chemo-radiotherapy (CRT) regimen in patients suffering
      from locally advanced rectal cancer. METHODS: Between June 2000 and April 2006,
      76 patients with locally advanced (cT3-4 N0/+) rectal adenocarcinoma were treated
      with HT plus CRT. HT was given once a week, to a total of five treatments, 1 to 4
      h after radiotherapy (50 Gy with 2-Gy fractions for 5 weeks, plus a 10-Gy boost
      on the tumour bed, with the same fractionation schedule). Chemotherapy consisted
      in 5FU 200 mg/m(2) continuous infusion throughout the 6 weeks of irradiation and
      OXA 45 mg/m(2) in a weekly bolus. Surgery followed 4 to 6 weeks after the
      completion of HT plus CRT. RESULTS: HT plus CRT was generally well tolerated. At
      pathologic examination, there was a pathologic complete response (pCR) (ypT0
      ypN0) in 18 out of 76 patients (23.6%), a partial response (PR) in 34/76 ones
      (44.7%) and a stable disease (SD) in 20/76 (26.3%) ones; 4/76 patients (5.2%) had
      a progression disease (PD) (distant metastases) at the time of surgery. Good
      predictors of a longer disease-free survival (DFS) were in order ypN status (log
      rank test: p = 0.0008), ypT status (p = 0.002) and pCR (p = 0.03). CONCLUSION:
      Preoperative CRT combined with regional HT yielded acceptable toxicity. The rate
      of pCR was encouraging, although further studies are needed to prove the long
      term efficacy of adding HT to CRT.

PMID- 20146566
TI  - Regional abdominal hyperthermia combined with systemic chemotherapy for the
      treatment of patients with ovarian cancer relapse: Results of a pilot study.
AB  - PURPOSE: Due to the poor prognosis of patients with ovarian cancer relapse (OCR),
      newer strategies are warranted to improve the therapeutic index. We performed a
      prospective phase I/II-study of regional abdominal hyperthermia (RHT) combined
      with systemic chemotherapy in OCR patients in order to evaluate outcome, efficacy
      and tolerance. MATERIALS AND METHODS: OCR patients with an Eastern Cooperative
      Oncology Group status <2, without any thromboembolic disease or severe
      cardiovascular co-morbidities, and pre-treated with at least one systemic
      chemotherapy regimen due to epithelial ovarian cancer were enrolled into the
      present study. RHT was applied using a SIGMA 60 applicator and a Hybrid-System
      SIGMA-Eye/MRT composed of a 1.5T-MRT and a Sigma-Eye-applicator. RESULTS:
      Overall, 36 OCR patients were enrolled. The majority of the patients (>80%) were
      classified as platinum resistant. The most common chemotherapeutic agent applied
      was pegylated-liposomal-doxorubicin (47.2%) followed by carboplatin (16.6%) and
      topotecan (13.9%). One patient (2.8%) achieved a complete remission (CR), 12
      patients (33.3%) yielded a partial remission (PR) and 16 patients (44.4%)
      developed a progressive disease (PD). In platinum-sensitive patients we observed
      higher response (57.1% versus 31%) and lower progression rates (28.6% versus
      48.3%) than in platinum-resistant patients. Eleven patients (30.5%) discontinued
      treatment due to toxicity. The main toxicity was a haematological one with grade
      3/4 anaemia, leucopenia and thrombocytopenia occurring in 13.9%, 5.6% and 8.3%,
      respectively. Median overall survival was 12 months (range: 1-48), while median
      progression-free survival was 5 months (range: 0.5-34). CONCLUSIONS: Our results
      demonstrate the feasibility of RHT combined with systemic treatment. Prospective
      phase III trials are warranted to evaluate the benefit and efficacy in heavily
      pre-treated patients with OCR.

PMID- 20146567
TI  - Thermochemotherapy in patients with extremity high-risk soft tissue sarcomas (HR
      STS).
AB  - PURPOSE: We report data from phase II trials examining the efficacy of
      multimodality treatment with neoadjuvant chemotherapy, hyperthermia, surgery,
      radiation and postoperative thermochemotherapy in adult patients with high-risk
      sarcomas of the extremities. PATIENTS AND METHODS: From 1991 to 2001 47 patients
      with high risk soft tissue sarcoma of the extremities were prospectively treated
      in two clinical trials with a treatment plan of four cycles of etoposide,
      ifosfamide and doxorubicin combined with regional hyperthermia followed by
      surgery, radiation and adjuvant chemotherapy. RESULTS: Objective response rate
      assessable in 39 patients was 21% (one complete and seven partial responses). A
      favourable histological response (>75% tumour necrosis) was observed in 34% of
      the 35 evaluable patients who had surgical resection. Median overall survival
      (OS) was 105 months. The five-year probability of local failure-free survival
      (LFFS), distant disease-free survival (DDFS), event-free survival (EFS) and OS
      were 48%, 55%, 35% and 57%, respectively. There were no significant differences
      between responders and non-responders of minimum temperatures (Tmin) and time
      averaged temperatures achieved in 50% (T(50)) and 90% (T(90)) at all measured
      tumour sites. Response to this neoadjuvant regimen predicted for prolonged LFFS
      (p = 0.0123), but not for OS (p = 0.2). Limb preservation was achieved in 37
      patients (79%) and did not result in inferior DDFS (52% versus 50%) or OS (61%
      versus 50%) at five years (p = 0.8) in comparison to patients who underwent
      amputation. CONCLUSION: Response to combined modality treatment with RHT and
      neoadjuvant chemotherapy was predictive for an improved LFFS and led to limb
      preservation in 79% of patients with extremity sarcomas.

PMID- 20146568
TI  - Elective re-irradiation and hyperthermia following resection of persistent
      locoregional recurrent breast cancer: A retrospective study.
AB  - PURPOSE: To analyse the therapeutic effect and toxicity of re-irradiation (re-RT)
      combined with hyperthermia (HT) following resection or clinically complete
      remission (CR) of persistent locoregional recurrent breast cancer in previously
      irradiated area. METHODS AND MATERIALS: Between 1988 and 2001, 78 patients with
      high risk recurrent breast cancer underwent elective re-RT and HT. All patients
      received extensive previous treatments, including surgery and high-dose
      irradiation (> or =50Gy). Most had received one or more lines of systemic
      therapy; 44% had been treated for > or = one previous locoregional recurrences.
      At start of re-RT + HT there was no macroscopically detectable tumour following
      surgery (96%) or chemotherapy (CT). Re-RT typically consisted of eight fractions
      of 4Gy, given twice weekly. Hyperthermia was added once a week. RESULTS: After a
      median follow up of 64.2 months, three-year survival was 66%. Three- and five
      year local control rates were 78% and 65%. Acute grade 3 toxicity occurred in 32%
      of patients. The risk of late > or = grade 3 toxicity was 40% after three years.
      Time interval to the current recurrence was found to be most predictive for local
      control in univariate and multivariate analysis. The extensiveness of current
      surgery was the most relevant treatment related factor associated with toxicity.
      CONCLUSIONS: For patients experiencing local recurrence in a previously radiated
      area, re-irradiation plus hyperthermia following minimisation of tumour burden
      leads to a high rate of local control, albeit with significant toxicity. The
      latter might be reduced by a more fractionated re-RT schedule.

PMID- 20146569
TI  - Clinical implementation of hyperthermia treatment planning guided steering: A
      cross over trial to assess its current contribution to treatment quality.
AB  - PURPOSE: To assess the current feasibility of online hyperthermia treatment
      planning guided steering (HGS) and its current contribution to treatment quality
      in deep hyperthermia for locally advanced cervical cancer. MATERIALS AND METHODS:
      36 patients were randomized to receive either their second and fourth (arm A) or
      their third and fifth (arm B) hyperthermia treatment of the series with the aid
      of HGS. The other treatments were conducted according to the Rotterdam Empirical
      Steering Guidelines (RESG). RESULTS: During period I (second and third treatment
      of the series) similar results were found for HGS and RESG with a slight, non
      significant difference found in favour of HGS. The average temperature T50 was
      40.3 degrees C for both (p = 0.409) and the dose parameter CEM43T90 was 0.64 for
      RESG and 0.63 for HGS (p = 0.154). However, during period II (fourth and fifth
      treatment of the series) HGS performed less well, with significant lower thermal
      dose parameters, minimum, mean and maximum intraluminal temperatures, tolerance
      measures and net integrated power. T50 was 40.4 degrees C after RESG and 40
      degrees C after HGS (p = 0.001) and CEM43T90 0.57 and 0.38 (p = 0.01)
      respectively. CONCLUSION: We found that the procedure of online treatment
      planning guided steering is feasible. For maximal exploitation of its
      possibilities, however, better control and understanding of several patient,
      tumour and technical parameters is required. This study has been very helpful in
      identifying some of the challenges and flaws that warrant further investigation
      in the near future, such as patient positioning and the prevention of hotspot
      related complaints.

PMID- 20146570
TI  - Design and test of a 434 MHz multi-channel amplifier system for targeted
      hyperthermia applicators.
AB  - PURPOSE: For our head-and-neck hyperthermia (HT) applicator, an amplifier system
      with full amplitude and phase-control to deliver the radio-frequency signals, was
      not available. We therefore designed and tested a 433.92 MHz multi-channel
      amplifier system. SYSTEM DESCRIPTION: The design consists of a direct digital
      synthesizer (DDS) system that generates 12 phase-controlled coherent 433.92 MHz
      signals, which are amplified to maximum 200 W output per channel. Directional
      couplers are placed at the amplifiers to couple a small portion of both forward
      and reflected signals to gain-and-phase detectors. The power setting is applied
      with a resolution of 2 W and for the phase it is 0.1 degrees . The channels are
      sequentially sampled at 100 Hz per channel. METHODS: We tested the performance of
      the designed amplifier system by measuring the RF spectrum, power and phase
      accuracy, and by characterising the feedback control by using highly accurate
      power and phase meters. RESULTS: The spurious emission is less than 60 dBc and
      the first two harmonic frequencies are suppressed more than 45 dB. The
      measurement accuracy for the power (+/-5%) is valid for at least 20 days after
      calibration and for the phase (+/-5 degrees ) it is valid for at least 2 months.
      CONCLUSIONS: The amplifier system operates according to our design criteria to
      support targeted HT. It can be used for both our in-house developed superficial
      and head-and-neck HT applicators or any other HT applicator that works on the
      same frequency of 433.92 MHz.

PMID- 20146571
TI  - SAR deposition by curved CFMA-434 applicators for superficial hyperthermia:
      Measurements and simulations.
AB  - INTRODUCTION: Contact flexible microstrip applicators (CFMA) are applied for
      superficial hyperthermia. In the clinic these flexible applicators are mostly
      applied bent along the body curvature. This paper investigates the specific
      absorption rate (SAR) patterns of CFMA applicators, when bent around an
      elliptical tissue-equivalent phantom. METHODS: The 2H (aperture size 14.8 x 14.3
      cm(2)), 3H (28.7 x 20.7 cm(2)), 4H (19.6 x 19.6 cm(2)) and 5H (19.7 x 28.5 cm(2))
      applicators were examined. Measurements were performed for the 5H applicator;
      existing measurement data were analysed for the 3H applicator. Finite difference
      time domain (FDTD) simulations with a resolution of 2 x 2 x 1 mm(3) were
      performed for all applicators. Applicators were bent around the top and the side
      of the elliptical phantom to examine different curvatures. The SAR deposition,
      effective field size (EFS) and effective heating depth (EHD) were evaluated and
      compared to results for straight applicators. RESULTS: Bending the applicators
      generally yielded a focusing effect of the SAR, which was most pronounced with a
      strong curvature, but especially the 5H applicator showed a stronger power
      absorption at the sides of the applicator, compared to the centre region. The EFS
      became smaller when bending the applicators; this effect was also more pronounced
      for a strong curvature. The EHD increased for bent applicators, but the degree
      depended strongly on the location. CONCLUSION: The behaviour of bent CFMA
      applicators is not trivial and the SAR deposition is not similar for all
      applicators. The EFS decreases and the EHD increases, but very locally.
      Therefore, it is generally advisable to analyse the SAR distribution of flexible
      applicators in both straight and bent state.

PMID- 20146572
TI  - Evaluation of a patch antenna applicator for time reversal hyperthemia.
AB  - PURPOSE: To describe the design, analysis and evaluation of a new antenna array
      system for microwave hyperthermia. The proposed antenna array was evaluated by
      the focusing method based on the time-reversal principle. MATERIALS AND METHODS:
      Power absorption distributions in a cylindrical homogeneous and inhomogeneous
      phantom were calculated for the frequency range 500-900 MHz. Two set-ups with 12
      and 16 antennas were analysed by comparing the changes in focusing areas enclosed
      by the 50%, 75% and 90% iso-SAR contours. For a more quantitative evaluation of
      the results the average power absorption ratio and remaining tissue maximum index
      were calculated. RESULTS: The sharpest focusing area in the centre of the
      phantom, 151 mm(2) (9 x 20 mm) (90% iso-SAR), was obtained by using 16 antennas
      at frequency 900 MHz. The largest focusing area of 280 mm(2) (13 x 24 mm) (90%
      iso-SAR) was obtained by using 16 antennas at 500 MHz. The SAR focus was steered
      in the desired radial direction obtaining a 43 mm(2) 90% iso-SAR focus-width in a
      semi-three-dimensional neck phantom. The results showed qualitative agreement
      between three dimensions (3D) and two dimensions (2D) for the performance
      indicators. CONCLUSIONS: The conducted study confirms the feasibility of the time
      reversal-based focusing methods for microwave hyperthermia. The proposed system
      shows promise and is suitable for further development in the treatment of head
      and neck tumours, and extremities application.

PMID- 20146573
TI  - Minimisation of HIFU pulse heating and interpulse cooling times.
AB  - This study presents results from a new optimisation technique that reduces HIFU
      treatment times by minimising individual heating and interpulse cooling times
      while adhering to normal tissue constraint limits at each sonication position.
      The potential clinical usefulness of this technique is demonstrated through its
      implementation in three dimentsional (3D) simulations of HIFU treatments for a
      range of tumour geometries, normal tissue constraint values, tissue perfusion
      levels and focal zone scanning path trajectories, all studied as a function of
      the applied power magnitude. When compared to typical open loop values the
      optimised treatment times were lower for all conditions studied, including when
      treatment-limiting normal tissue thermal build-up was present. While use of this
      technique guarantees minimum pulse heating and interpulse cooling times for each
      pulse, the total treatment time gains realised depend on the individual clinical
      treatment configuration. In combination with a judiciously selected scan path,
      use of the pulse time optimisation procedure reduced treatment times in a small,
      superficial tumour by 85%. In addition, in all cases studied the use of an
      increased applied power always decreased the treatment time, including cases when
      significant normal tissue thermal build-up was present. Importantly, the power
      maximisation and pulse time minimisation procedures can be applied independently
      of the optimisation of the focal zone's scan path, size and shape. Given the
      basic nature, universal applicability and ready clinical adaptability for use in
      real time model predictive control, the pulse time minimisation and power
      maximisation approaches have significant clinical promise for reducing HIFU
      treatment times.

PMID- 20146575
TI  - Increasing incidence of thyroid cancer: is diagnostic scrutiny the sole
      explanation?

PMID- 20146576
TI  - Small soldiers combine arms to go to war on tumor cells.

PMID- 20146574
TI  - Correlates of sexual functioning in Italian menopausal women.
AB  - OBJECTIVES: To analyze the sexuality of Italian menopausal women. DESIGN: Cross
      sectional study. POPULATION: Menopausal women consecutively observed during the
      study period in menopause clinics. METHODS: Women were interviewed about their
      current and premenopausal sexual activity: sexual intercourse frequency and self
      rated sexual desire, capacity for orgasm and sexual satisfaction were recorded.
      Women were defined as having poor sexual functioning if they had one or less
      sexual intercourses per week or answered 'absent/poor' to the questions about the
      sexual domains. RESULTS: Oral hormone therapy (HT) use (odds ratio (OR) 0.43 for
      desire, 0.54 for orgasm and 0.56 for overall sexual satisfaction, all p < 0.001)
      and transdermal HT (OR 0.38, 0.53 and 0.53, respectively, all p < 0.001) were
      significantly associated with lower risk of poor sexual functioning. Higher
      physical and mental component scores (PCS and MCS, range 0-100) of the Short Form
      12 are inversely related to poor sexual functioning (OR by point 0.96, 0.95, 0.95
      for PCS and 0.96, 0.96 and 0.95, for MCS, respectively, all p < 0.001). Pain
      during and symptoms after sexual intercourse were significantly related to desire
      (OR 1.96 and 1.78, respectively), orgasm (OR 2.22 and 2.06, respectively) and
      sexual satisfaction (OR 2.02 and 1.79, respectively). The partner's health
      problems were associated with low sexual intercourse frequency (OR 4.18, p <
      0.001) and absent/poor overall satisfaction (OR 2.61, p < 0.001). CONCLUSIONS:
      This study shows that, in menopausal Italian women attending menopause clinics,
      sexual function is associated with the quality of sexual life in reproductive
      age, partner's health status, current quality of life, HT and occurrence of pain
      during and symptoms after sexual intercourse.

PMID- 20146577
TI  - Targeting chemotherapy to advanced bladder cancer patients most likely to
      benefit.
AB  - Evaluation of: Vickers AJ, Cronin AM, Kattan MW et al.; The International Bladder
      Cancer Nomogram Consortium: Clinical benefits of a multivariate prediction model
      for bladder cancer: a decision analytic approach. Cancer 115(23), 5460-5469
      (2009). The prognosis from muscle-invasive bladder cancer is poor. Improvements
      in survival can be made with the use of chemotherapy. The best results are
      obtained using multiagent regimens, which increase cure rates by approximately
      5%. Thus, few patients benefit when compared with treatment morbidity. This low
      complete response rate makes powering of clinical trials difficult and may
      prevent them determining which patients benefit most from chemotherapy. Here, we
      discuss work by Vickers et al. reporting a decision-based analysis using a
      nomogram to determine the benefit for individual patients from chemotherapy. This
      decision aid can reduce the number of patients treated by 0.006, without
      compromising recurrence. The authors conclude that a nomogram-derived 25% risk
      threshold produced better targeting of chemotherapy than the current standard
      criteria (mostly using pathological stage).

PMID- 20146578
TI  - Aspirin: anticolorectal adenocarcinoma activity in the adjuvant arena?
AB  - Evaluation of: Chan AT, Ogino S, Fuchs CS: Aspirin use and survival after
      diagnosis of colorectal cancer. JAMA 302, 649-659 (2009). Colorectal cancer (CRC)
      is the second most common cause of cancer-related deaths in Americans. In prior
      observational studies, aspirin has been associated with significant reductions in
      colorectal adenoma recurrence, CRC incidence, CRC-associated mortality and
      overall mortality. In this study of data from two large, long-term cohort
      studies, Chan et al. identify significant inverse associations in both CRC
      related mortality and overall mortality among patients with stage I-III CRC using
      aspirin versus nonusers. The absolute risk reductions in both parameters in
      aspirin users are in the order of 4%, but aspirin's potential benefits are
      restricted to patients with COX-2-overexpressing tumors. The feasibility and
      impact of aspirin as an adjuvant therapy for nonmetastatic CRC needs confirmation
      in randomized trials to answer remaining questions regarding the most appropriate
      dose, frequency and duration of administration, as well as to estimate the
      relative benefits versus risks of treatment in this setting.

PMID- 20146579
TI  - Ixabepilone plus capecitabine with capecitabine alone for metastatic breast
      cancer.
AB  - AIM: We conducted a systematic review to estimate efficacy and safety of
      ixabepilone plus capecitabine compared with capecitabine alone for patients of
      anthracycline- and/or taxane-resistant metastatic breast cancer. MATERIALS &
      METHODS: PubMed, Cochrane Library, EMBASE, ClinicalTrials.gov and other databases
      were searched. Randomized controlled trials containing ixabepilone plus
      capecitabine for anthracycline- and/or taxane-resistant metastatic breast cancer
      were eligible. Studies were assessed for eligibility and quality, and data were
      extracted by two independent reviewers. Overall response rates and toxicity were
      analyzed as dichotomous variables. Overall survival and time to progression data
      were analyzed as inverse variables. Meta-analyses were carried out by Review
      Manager 5.0 Software. RESULTS: This report included two large clinical trials
      (1973 patients) for patients with metastatic breast cancer resistant to taxanes
      and resistant to or pretreated with anthracyclines. Ixabepilone plus capecitabine
      has prolonged the median time to progression, increased overall survival and
      significantly increased response rates compared with capecitabine alone. Adverse
      events observed with the combination arm were generally manageable and well
      tolerated with neutropenia and febrile neutropenia, and peripheral neuropathy,
      myalgia, diarrhea, stomatitis and hand-foot syndrome were easily controlled.
      CONCLUSION: Ixabepilone plus capecitabine demonstrated clinical activity with an
      acceptable safety profile, which seems to be a valid option for patients with
      anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer.

PMID- 20146580
TI  - Cytokeratin 19-positive circulating tumor cells in early breast cancer prognosis.
AB  - In spite of the heterogeneity of breast cancer at the molecular level,
      circulating tumor cells (CTCs) may provide a novel prognostic marker.
      Approximately 20-40% of early breast cancer patients have detectable CTCs using
      reverse transcription PCR for CK19. The detection of CTCs before adjuvant
      chemotherapy or during tamoxifen administration has been demonstrated to be an
      independent adverse prognostic factor in women with early-stage breast cancer.
      The prognostic value of CTC detection is of great significance in subgroups of
      patients with estrogen receptor-negative and human EGF receptor 2-positive
      tumors. Prospective clinical trials are warranted in order to validate the use of
      CTCs as predictive and/or prognostic markers and assess their utility in
      individualizing therapy of patients with early breast cancer.

PMID- 20146581
TI  - Neurotransmitter receptors as central regulators of pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has a near 100% mortality because it is
      generally detected at an advanced stage and responds poorly to existing
      therapeutics. This review summarizes current evidence suggesting important roles
      of neurotransmitter receptors in the regulation of this malignancy. Experimental
      evidence indicates that the alpha(7)-nicotinic acetylcholine receptor
      (alpha(7)nAChR) stimulates PDAC via stress neurotransmitter-mediated activation
      of beta-adrenergic signaling while the alpha(4)beta(2)nAChR inhibits PDAC via
      GABA-mediated inhibition of adenylyl cyclase activation. In analogy to molecular
      mechanisms that govern nicotine addiction, chronic exposure to nicotine or its
      nitrosated derivative nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      render the stimulatory alpha(7)nAChR hyperactive while desensitizing the
      inhibitory alpha(4)beta(2)nAChR. Accordingly, PDAC intervention strategies should
      include the diagnosis of unphysiological neurotransmitter levels and aim to
      restore any imbalance in stimulatory and inhibitory neurotransmitters.

PMID- 20146583
TI  - Clinical implications of MET gene copy number in lung cancer.
AB  - MET, the receptor for HGF, has recently been identified as a novel promising
      target in several human malignancies, including non-small-cell lung cancer
      (NSCLC). Deregulation of the HGF/MET signaling pathway can occur via different
      mechanisms, including HGF and/or MET overexpression, MET gene amplification,
      mutations or rearrangements. While the role of MET mutations in NSCLC is not yet
      fully understood, MET amplification emerged as a critical event in driving cell
      survival, with preclinical data suggesting that MET-amplified cell lines are
      exquisitely sensitive to MET inhibition. True MET amplification, which has been
      associated with poor prognosis in different retrospective series, is a relatively
      uncommon event in NSCLC, occurring in 1-7% of unselected cases. Nevertheless, in
      highly selected cohorts of patients, such as those harboring somatic mutations of
      the EGF receptor (EGFR) with acquired resistance to EGFR tyrosine kinase
      inhibitors (TKIs), MET amplification can be observed in up to 20% of cases.
      Preclinical data suggested that a treatment approach including a combination of
      EGFR and MET TKIs could be an effective strategy in this setting and led to the
      clinical investigation of multiple MET TKIs in combination with erlotinib.
      Results from ongoing and future trials will clarify the role of MET TKIs for the
      treatment of NSCLC and will provide insights into the most appropriate timing for
      their use.

PMID- 20146582
TI  - Insulinoma: pathophysiology, localization and management.
AB  - Insulinoma is a rare neuroendocrine tumor that causes oversecretion of insulin
      and, as a result, patients present with symptoms of hypoglycemia. Fortunately,
      insulinomas are usually benign and solitary, and surgical cure rates are highly
      favorable. Most of these tumors occur sporadically, but they can also be
      associated with multiple endocrine neoplasia type-1 syndrome. The diagnosis is
      confirmed by a supervised fast, and early detection is important. Several
      preoperative and intraoperative techniques with various success rates have been
      employed in order to localize the lesion. When technically feasible, tumor
      enucleation is the procedure of choice; however, a more formal resection may be
      necessary for certain tumors. In the age of laparoscopy, the role of laparoscopic
      surgery in the management of insulinomas is continuing to attract attention. This
      review will discuss the historical background, pathogenesis, diagnosis,
      localization and management of insulinomas.

PMID- 20146585
TI  - Is focal therapy the future for prostate cancer?
AB  - Focal therapy aims to find a middle ground between surveillance and radical
      therapies by treating the cancer alone, with a margin, and preserving as much
      tissue as is practical. Early feasibility studies have demonstrated an absence of
      rectal toxicity and preservation of genitourinary function in 80-90% of men. The
      incidence of low- to intermediate-risk prostate cancer is rising owing to
      informal and formal prostate-specific antigen screening practices. The treatment
      burden from radical therapies is high with over 50% of men suffering
      genitourinary or rectal toxicity. Active surveillance, on the other hand, carries
      surveillance and psychological burden with risk of progression. A research
      strategy to evaluate focal therapy should be embedded within pragmatic designs
      using a broad patient group, using the available ablative technologies
      (cryotherapy, high-intensity focused ultrasound, brachytherapy and photodynamic
      therapy) with end points derived from biochemical, biopsy and imaging. Within
      this framework there exists a unique opportunity to undertake landmark diagnostic
      studies incorporating imaging techniques and biomarkers in addition to studies
      directed at the biology of prostate cancer over time.

PMID- 20146586
TI  - Prognostic value and biological role of the kallikrein-related peptidases in
      human malignancies.
AB  - Cancer is a substantial health problem for the populations of the Western world.
      The discovery of new molecular biomarkers for diagnosis, prognosis and monitoring
      patients' response to therapy can aid in combating this complicated disease. The
      human kallikrein-related peptidases (human tissue kallikreins [KLKs]) are encoded
      by a continuous multigene family, located on chromosomal region 19q13.3-4. KLK3
      (prostate-specific antigen) is the most efficient cancer biomarker ever employed.
      KLK genes are expressed abnormally in various malignancies, where they affect
      cancer-cell growth and metastasis. Their deregulated expression pattern, often
      associated with various clinicopathological characteristics of cancer patients,
      can be exploited, solely or within multiparametric panels, as a prognostic
      biomarker. Recent data illustrate that discernible molecular modulations of KLKs,
      occurring as a result of cancer cells' treatment with antitumor agents, may serve
      as new potential biomarkers, possibly predicting patients' treatment response. It
      is believed that KLKs might be employed in future clinical practice as novel and
      effective tumor markers.

PMID- 20146587
TI  - Known and emerging biomarkers of leptomeningeal metastasis and its response to
      treatment.
AB  - Leptomeningeal metastasis (LM) is the metastatic dissemination of malignant cells
      to the leptomeninges and the subarachnoid space of the CNS, affecting
      approximately 8% of all cancer patients. Cerebrospinal fluid cytology is
      currently the gold standard for diagnosis of LM and assessment of treatment
      response, but it has relatively low sensitivity. Thus, specific biomarkers of LM
      may allow for earlier diagnosis and treatment. This article reviews known tumor
      markers for LM and describes recent work to find LM-specific markers, such as
      angiogenesis-related proteins. Novel methods of protein profiling that may aid
      this search are also described; these methods still need to be standardized and
      validated to gain widespread acceptance. Nevertheless, we anticipate that future
      biomarkers will have not only the potential to detect LM, but to predict its
      progression and response to treatment.

PMID- 20146584
TI  - WWOX gene and gene product: tumor suppression through specific protein
      interactions.
AB  - The WWOX gene, an archetypal fragile gene, encompasses a chromosomal fragile site
      at 16q23.2, and encodes the approximately 46-kDa Wwox protein, with WW domains
      that interact with a growing list of interesting proteins. If the function of a
      protein is defined by the company it keeps, then Wwox is involved in numerous
      important signal pathways for bone and germ-cell development, cellular and animal
      growth and death, transcriptional control and suppression of cancer development.
      Because alterations to genes at fragile sites are exquisitely sensitive to
      replication stress-induced DNA damage, there has been an ongoing scientific
      discussion questioning whether such gene expression alterations provide a
      selective advantage for clonal expansion of neoplastic cells, and a parallel
      discussion on why important genes would be present at sites that are susceptible
      to inactivation. We offer some answers through a description of known WWOX
      functions.

PMID- 20146588
TI  - Oral cancer screening: what have we learnt and what is there still to achieve?
AB  - Oral cancer is an important global healthcare problem. In the UK, the incidence
      is increasing and late-stage presentation is common. Determining the feasibility
      of a national screening program for oral cancer is therefore an important step in
      the prevention of the disease. Evidence exists to suggest that an oral
      examination of high-risk individuals may be a cost-effective screening strategy.
      However, questions remain over which primary care environment would be the most
      suitable and the criteria for a positive screen and referral. Further research is
      needed in the form of clinical trials or demonstration studies in primary care.
      The impact on secondary care, the role of auxiliaries and training needs also
      need to be determined. In addition, the assessment of adjunctive aids and
      evaluation of potential biomarkers are considered important.

PMID- 20146589
TI  - Role of PET/CT imaging in stereotactic body radiotherapy.
AB  - Stereotactic body radiotherapy (SBRT) is a relatively new technique that enables
      delivery of high doses of radiation to malignancies throughout the body with a
      higher degree of precision than conventional radiation modalities. PET and
      computed tomography are rapidly being adopted for the evaluation of patients with
      cancer, and its role in conjunction with SBRT is under active investigation. This
      article reviews the literature regarding the utility of PET and computed
      tomography in treatment planning, follow-up imaging, relationship with clinical
      outcomes, and other topics in patients treated with SBRT. These questions are
      investigated for cancers of the lung, head and neck, pancreas and liver. A brief
      overview of various commercially available SBRT treatment systems is also
      included.

PMID- 20146590
TI  - Disparities in uterine cancer survival in a Brooklyn cohort of black women.
AB  - AIM: The present study evaluates uterine cancer survival in a black cohort living
      in Brooklyn and determines whether foreign-born women have a health benefit over
      those born in the USA. MATERIALS & METHODS: De-identified cancer registry data
      were obtained for all black patients (n = 311) diagnosed with primary uterine
      cancer between 1993 and 2007. Survival rates were analyzed according to place of
      birth. RESULTS: The 5-year survival rate was slightly higher for US-born black
      patients; the predictors of overall survival were different for foreign-born
      black women compared with US-born black women. Age was a predictor of death in US
      born women and type of treatment was a predictor in foreign-born women.
      CONCLUSION: This study demonstrates that grouping together US-born and foreign
      born black patients may mask important differences within the black population.
      The observed differences between US-born and foreign-born black patients may be
      associated with variations in environmental and other lifestyle exposures that
      contribute to more aggressive histologic types.

PMID- 20146592
TI  - Activating without inhibiting: left-edge boundary tones and syntactic processing.
AB  - Right-edge boundary tones have earlier been found to restrict syntactic
      processing by closing a clause for further integration of incoming words. The
      role of left-edge intonation, however, has received little attention to date. We
      show that Swedish left-edge boundary tones selectively facilitate the on-line
      processing of main clauses, the syntactic structure they are associated with. In
      spoken Swedish, main clauses are produced with a left-edge boundary tone, which
      is absent in subordinate clauses. Main and subordinate clauses are further
      distinguished syntactically by word order when containing sentence adverbs. The
      effects of tone and word order on the processing of embedded main, subordinate,
      and neutral clauses (lacking sentence adverbs) were measured using ERPs. A
      posterior P600 in embedded main clauses and a smaller P600 in subordinate clauses
      indicated that embedded clauses with sentence adverbs were structurally less
      expected than neutral clauses and thus were reanalyzed. The tone functioned as a
      cue for main clause word order, selectively reducing the P600 in embedded main
      clauses, without affecting the processing of subordinate or neutral clauses. Its
      perception was reflected in a right frontal P200 effect. The left-edge boundary
      tone thus seems to activate a main clause structure, albeit without suppressing
      alternative structures. The P600 was also preceded by a short positive effect in
      cases where a left-edge boundary tone was absent.

PMID- 20146593
TI  - Slow fluctuations in attentional control of sensory cortex.
AB  - Top-down control of visual sensory cortex has long been tied to the orienting of
      visual spatial attention on a rapid, moment-to-moment basis. Here, we examined
      whether sensory responses in visual cortex are also modulated by natural and
      comparatively slower fluctuations in whether or not one is paying attention to
      the task at hand. Participants performed a simple visual discrimination task at
      fixation as the ERPs to task-irrelevant probes in the upper visual periphery were
      recorded. At random intervals, participants were stopped and asked to report on
      their attentional state at the time of stoppage-either "on-task" or "off-task."
      ERPs to the probes immediately preceding these subjective reports were then
      examined as a function of whether attention was in an on-task versus off-task
      state. We found that sensory-evoked responses to the probes were significantly
      attenuated during off-task relative to on-task states, as measured by the visual
      P1 ERP component. In two additional experiments, we replicated this effect while
      (1) finding that off-task sensory attenuation extends to the auditory domain, as
      measured by the auditory N1 ERP component, and (2) eliminating state-dependent
      shifts in general arousal as a possible explanation for the effects.
      Collectively, our findings suggest that sensory gain control in cortex is yoked
      to the natural ebb and flow in how much attention we pay to the current task over
      time.

PMID- 20146594
TI  - From perception to recognition memory: time course and lateralization of neural
      substrates of word and abstract picture processing.
AB  - Through study of clinical cases with brain lesions as well as neuroimaging
      studies of cognitive processing of words and pictures, it has been established
      that material-specific hemispheric specialization exists. It remains however
      unclear whether such specialization holds true for all processes involved in
      complex tasks, such as recognition memory. To investigate neural signatures of
      transition from perception to recognition, according to type of material (words
      or abstract pictures), high-resolution scalp ERPs were recorded in adult humans
      engaged either in categorization or in memory recognition tasks within the same
      experimental setup. Several steps in the process from perception to recognition
      were identified. Source localization showed that the early stage of perception
      processing (N170) takes place in the fusiform gyrus and is lateralized according
      to the nature of stimuli (left side for words and right side for pictures). Late
      stages of processing (N400/P600) corresponding to recognition are material
      independent and involve anterior medial-temporal and ventral prefrontal
      structures bilaterally. A crucial transitional process between perception (N170)
      and recognition (N400/P600) is reflected by the N270, an often overlooked
      component, which occurs in anterior rhinal cortices and shows material-specific
      hemispheric lateralization.

PMID- 20146595
TI  - Material-specific neural correlates of recollection: objects, words, and faces.
AB  - It is unclear how neural correlates of episodic memory retrieval differ depending
      on the type of material that is retrieved. Here, we used a source memory task to
      compare electrical brain activity for the recollection of three types of stimulus
      material. At study, healthy adults judged how well visually presented objects,
      words, and faces fitted with paired auditorily presented names of locations. At
      test, only visual stimuli were presented. The task was to decide whether an item
      had been presented earlier and, if so, what location had been paired with the
      item. Stimulus types were intermixed across trials in Experiment 1 and presented
      in separate study-test lists in Experiment 2. A graded pattern of memory
      performance was observed across objects, words, and faces in both experiments.
      Between 300 and 500 msec, event-related potentials for recollected objects and
      faces showed a more frontal scalp distribution compared to words in both
      experiments. Later in the recording epoch, all three stimulus materials elicited
      recollection effects over left posterior scalp sites. However, these effects
      extended more anteriorly for objects and faces when stimulus categories were
      blocked. These findings demonstrate that the neural correlates of recollection
      are material specific, the crucial difference being between pictorial and verbal
      material. Faces do not appear to have a special status. The sensitivity of
      recollection effects to the kind of experimental design suggests that, in
      addition to type of stimulus material, higher-level control processes affect the
      cognitive and neural mechanisms underlying episodic retrieval.

PMID- 20146596
TI  - Cue competition affects temporal dynamics of edge-assignment in human visual
      cortex.
AB  - Edge-assignment determines the perception of relative depth across an edge and
      the shape of the closer side. Many cues determine edge-assignment, but relatively
      little is known about the neural mechanisms involved in combining these cues.
      Here, we manipulated extremal edge and attention cues to bias edge-assignment
      such that these two cues either cooperated or competed. To index their neural
      representations, we flickered figure and ground regions at different frequencies
      and measured the corresponding steady-state visual-evoked potentials (SSVEPs).
      Figural regions had stronger SSVEP responses than ground regions, independent of
      whether they were attended or unattended. In addition, competition and
      cooperation between the two edge-assignment cues significantly affected the
      temporal dynamics of edge-assignment processes. The figural SSVEP response peaked
      earlier when the cues causing it cooperated than when they competed, but
      sustained edge-assignment effects were equivalent for cooperating and competing
      cues, consistent with a winner-take-all outcome. These results provide
      physiological evidence that figure-ground organization involves competitive
      processes that can affect the latency of figural assignment.

PMID- 20146597
TI  - Accessing semantic person knowledge: temporal dynamics of nonstrategic
      categorical and associative priming.
AB  - Recent theories of semantic memory suggest a subdivision into several separate
      domains of knowledge. The present study examined the structure of semantic person
      knowledge by analyzing both behavioral and ERP correlates of associative priming
      (via co-occurrence and/or shared semantic information) versus purely categorical
      priming (via shared occupational information). Participants performed familiarity
      decisions for target faces, which were preceded by sandwich-masked prime names at
      either short (33 msec) or long (1033 msec) SOAs. Although masking effectively
      prevented explicit prime recognition, faster RTs were generally observed for both
      associative and categorical priming (relative to an unrelated prime-target
      condition). At the short SOA, both associatively and categorically primed targets
      similarly elicited more positive going ERPs compared with unrelated targets in
      the N400 time range (N400 priming effect), suggesting a common initial mechanism
      mediating both forms of priming. By contrast, at the long SOA, a typical N400
      priming effect was observed for associative priming only, whereas the
      corresponding effect for categorical priming was small and restricted to a left
      parietal site. This hitherto unreported interaction of relatedness, and SOA in
      the N400 suggests an initial fast spreading of activation to a wide range of
      related targets, which subsequently focuses to more closely related people at
      longer SOAs. This ability of ERPs to trace the neural dynamics of activation for
      different forms of prime/target relatedness can be exploited for testing
      different models of semantic priming.

PMID- 20146598
TI  - Dynamic coding of events within the inferior frontal gyrus in a probabilistic
      selective attention task.
AB  - Besides the fact that RTs in cognitive tasks are affected by the specific demands
      of a trial, the context in which this trial occurs codetermines the speed of the
      response. For instance, invalid spatial cues generally prolong RTs to targets in
      the location-cueing paradigm, whereas the magnitude of these RT costs
      additionally varies as a function of the preceding trial types so that RTs for
      invalid trials may be increased when preceded by valid rather than invalid
      trials. In the present fMRI study, we investigated trial sequence effects in a
      combined oddball and location-cueing paradigm. In particular, we tested whether
      RTs and neural activity to infrequent invalid or deviant targets varied as a
      function of the number of preceding valid standard trials. As expected, RTs in
      invalid and deviant trials were significantly slower when more valid standard
      trials had been presented beforehand. This behavioral effect was reflected in the
      neural activity of the right inferior/middle frontal gyrus where the amplitude of
      the hemodynamic response in invalid and deviant trials was positively related to
      the number of preceding valid standard trials. In contrast, decreased activity
      (i.e., a negative parametric modulation effect) was observed when more valid
      standard trials were successively presented. Further positive parametric effects
      for the number of preceding valid standard trials were observed in the left
      caudate nucleus and lingual gyrus. The data suggest that inferior frontal cortex
      extracts both event regularities and irregularities in event streams.

PMID- 20146599
TI  - Decreased visual attention further from the perceived direction of gaze for
      equidistant retinal targets.
AB  - The oculomotor and spatial attention systems are interconnected. Whereas a link
      between motor commands and spatial shifts in visual attention is demonstrated, it
      is still unknown whether the recently discovered proprioceptive signal in
      somatosensory cortex impacts on visual attention, too. This study investigated
      whether visual targets near the perceived direction of gaze are detected more
      accurately than targets further away, despite the equal eccentricity of their
      retinal projections. We dissociated real and perceived eye position using left
      somatosensory repetitive transcranial magnetic stimulation (rTMS), which
      decreases cortical processing of eye muscle proprioceptive inflow and produces an
      underestimation of the rotation of the right eye. Participants detected near
      threshold visual targets presented in the left or right visual hemifield at equal
      distance from fixation. We have previously shown that when the right eye is
      rotated to the left of the parasagittal plane, TMS produces an underestimation of
      this rotation, shifting perceived eye position to the right. Here we found that,
      in this condition, TMS also decreased target detection in the left visual
      hemifield and increased it in the right. This effect depended on the direction of
      rotation of the right eye. When the right eye was rotated rightward and TMS, we
      assume, shifted perceived gaze direction in opposite direction, leftward, visual
      accuracy decreased now in the right hemifield. We suggest that the proprioceptive
      eye position signal modulates the spatial distribution of visual processing
      resources, producing "pseudo-neglect" for objects located far relative to near
      the perceived direction of gaze.

PMID- 20146600
TI  - Assembly and use of new task rules in fronto-parietal cortex.
AB  - Severe capacity limits, closely associated with fluid intelligence, arise in
      learning and use of new task rules. We used fMRI to investigate these limits in a
      series of multirule tasks involving different stimuli, rules, and response keys.
      Data were analyzed both during presentation of instructions and during later task
      execution. Between tasks, we manipulated the number of rules specified in task
      instructions, and within tasks, we manipulated the number of rules operative in
      each trial block. Replicating previous results, rule failures were strongly
      predicted by fluid intelligence and increased with the number of operative rules.
      In fMRI data, analyses of the instruction period showed that the bilateral
      inferior frontal sulcus, intraparietal sulcus, and presupplementary motor area
      were phasically active with presentation of each new rule. In a broader range of
      frontal and parietal regions, baseline activity gradually increased as successive
      rules were instructed. During task performance, we observed contrasting fronto
      parietal patterns of sustained (block-related) and transient (trial-related)
      activity. Block, but not trial, activity showed effects of task complexity. We
      suggest that, as a new task is learned, a fronto-parietal representation of
      relevant rules and facts is assembled for future control of behavior. Capacity
      limits in learning and executing new rules, and their association with fluid
      intelligence, may be mediated by this load-sensitive fronto-parietal network.

PMID- 20146601
TI  - Attentional control in anterior cingulate cortex based on probabilistic cueing.
AB  - In Stroop-like tasks, conflict effects in behavioral measures and ACC activity
      are smaller on trials following an incongruent trial than following a congruent
      one. Researchers have found no agreement on whether these sequential effects in
      ACC can be driven by experienced incongruency only or also by expectations about
      target types. In the present fMRI experiment, we specifically manipulated the
      expectancies by using symbolic cues predicting with 75% or 50% certainty the
      incongruent or congruent targets in a Stroop-like task. Both behavioral and
      dorsal ACC data replicated previous sequential effects, with conflict effects
      being smallest for targets following the cues that predicted with 75% certainty
      the incongruent targets. However, these effects were not driven by experienced
      conflict but by symbolic cues. These results demonstrate differential attentional
      control activity in ACC after probabilistic cueing, providing evidence for
      control adjustments driven by changes in expectation.

PMID- 20146602
TI  - Neural correlates of sequence learning with stochastic feedback.
AB  - Although much is known about decision making under uncertainty when only a single
      step is required in the decision process, less is known about sequential decision
      making. We carried out a stochastic sequence learning task in which subjects had
      to use noisy feedback to learn sequences of button presses. We compared flat and
      hierarchical behavioral models and found that although both models predicted the
      choices of the group of subjects equally well, only the hierarchical model
      correlated significantly with learning-related changes in the magneto
      encephalographic response. The significant modulations in the magneto
      encephalographic signal occurred 83 msec before button press and 67 msec after
      button press. We also localized the sources of these effects and found that the
      early effect localized to the insula, whereas the late effect localized to the
      premotor cortex.

PMID- 20146603
TI  - Auditory target detection is affected by implicit temporal and spatial
      expectations.
AB  - Mechanisms of implicit spatial and temporal orienting were investigated by using
      a moving auditory stimulus. Expectations were set up implicitly, using the
      information inherent in the movement of a sound, directing attention to a
      specific moment in time with respect to a specific location. There were four
      conditions of expectation: temporal and spatial expectation; temporal expectation
      only; spatial expectation only; and no expectation. Event-related brain
      potentials were recorded while participants performed a go/no-go task, set up by
      anticipation of the reappearance of a target tone through a white noise band.
      Results showed that (1) temporal expectations alone speeded reaction time and
      increased response accuracy; and (2) implicit temporal expectations alone
      independently enhanced target detection at early processing stages, prior to
      motor response. This was reflected at stages of perceptual analysis, indexed by
      P1 and N1 components, as well as in task-related stages indexed by N2; and (3)
      spatial expectations had an effect at later response-related processing stages
      but only in combination with temporal expectations, indexed by the P3 component.
      Thus, the results, in addition to indicating a primary role for temporal
      orienting in audition, suggest that multiple mechanisms of attention interact in
      different phases of auditory target detection. Our results are consistent with
      the view from vision research that spatial and temporal attentional control is
      based on the activity of partly overlapping, and partly functionally specialized
      neural networks.

PMID- 20146604
TI  - Early stages of figure-ground segregation during perception of the face-vase.
AB  - The temporal sequence of neural processes supporting figure-ground perception was
      investigated by recording ERPs associated with subjects' perceptions of the face
      vase figure. In Experiment 1, subjects continuously reported whether they
      perceived the face or the vase as the foreground figure by pressing one of two
      buttons. Each button press triggered a probe flash to the face region, the vase
      region, or the borders between the two. The N170/vertex positive potential (VPP)
      component of the ERP elicited by probes to the face region was larger when
      subjects perceived the faces as figure. Preceding the N170/VPP, two additional
      components were identified. First, when the borders were probed, ERPs differed in
      amplitude as early as 110 msec after probe onset depending on subjects' figure
      ground perceptions. Second, when the face or vase regions were probed, ERPs were
      more positive (at ~ 150-200 msec) when that region was perceived as figure versus
      background. These components likely reflect an early "border ownership" stage,
      and a subsequent "figure-ground segregation" stage of processing. To explore the
      influence of attention on these stages of processing, two additional experiments
      were conducted. In Experiment 2, subjects selectively attended to the face or
      vase region, and the same early ERP components were again produced. In Experiment
      3, subjects performed an identical selective attention task, but on a display
      lacking distinctive figure-ground borders, and neither of the early components
      were produced. Results from these experiments suggest sequential stages of
      processing underlying figure-ground perception, each which are subject to
      modifications by selective attention.

PMID- 20146605
TI  - Does sleep promote false memories?
AB  - Memory is constructive in nature so that it may sometimes lead to the retrieval
      of distorted or illusory information. Sleep facilitates accurate declarative
      memory consolidation but might also promote such memory distortions. We examined
      the influence of sleep and lack of sleep on the cerebral correlates of accurate
      and false recollections using fMRI. After encoding lists of semantically related
      word associates, half of the participants were allowed to sleep, whereas the
      others were totally sleep deprived on the first postencoding night. During a
      subsequent retest fMRI session taking place 3 days later, participants made
      recognition memory judgments about the previously studied associates, critical
      theme words (which had not been previously presented during encoding), and new
      words unrelated to the studied items. Sleep, relative to sleep deprivation,
      enhanced accurate and false recollections. No significant difference was observed
      in brain responses to false or illusory recollection between sleep and sleep
      deprivation conditions. However, after sleep but not after sleep deprivation
      (exclusive masking), accurate and illusory recollections were both associated
      with responses in the hippocampus and retrosplenial cortex. The data suggest that
      sleep does not selectively enhance illusory memories but rather tends to promote
      systems-level consolidation in hippocampo-neocortical circuits of memories
      subsequently associated with both accurate and illusory recollections. We further
      observed that during encoding, hippocampal responses were selectively larger for
      items subsequently accurately retrieved than for material leading to illusory
      memories. The data indicate that the early organization of memory during encoding
      is a major factor influencing subsequent production of accurate or false
      memories.

PMID- 20146606
TI  - Combining functional neuroimaging with off-line brain stimulation: modulation of
      task-related activity in language areas.
AB  - Repetitive TMS (rTMS) provides a noninvasive tool for modulating neural activity
      in the human brain. In healthy participants, rTMS applied over the language
      related areas in the left hemisphere, including the left posterior temporal area
      of Wernicke (LTMP) and inferior frontal area of Broca, have been shown to affect
      performance on word recognition tasks. To investigate the neural substrate of
      these behavioral effects, off-line rTMS was combined with fMRI acquired during
      the performance of a word recognition task. Twenty right-handed healthy men
      underwent fMRI scans before and after a session of 10-Hz rTMS applied outside the
      magnetic resonance scanner. Functional magnetic resonance images were acquired
      during the performance of a word recognition task that used English or foreign
      language words. rTMS was applied over the LTMP in one group of 10 participants
      (LTMP group), whereas the homologue region in the right hemisphere was stimulated
      in another group of 10 participants (RTMP group). Changes in task-related fMRI
      response (English minus foreign languages) and task performances (response time
      and accuracy) were measured in both groups and compared between pre-rTMS and post
      rTMS. Our results showed that rTMS increased task-related fMRI response in the
      homologue areas contralateral to the stimulated sites. We also found an effect of
      rTMS on response time for the LTMP group only. These findings provide insights
      into changes in neural activity in cortical regions connected to the stimulated
      site and are consistent with a hypothesis raised in a previous review about the
      role of the homologue areas in the contralateral hemisphere for preserving
      behavior after neural interference.

PMID- 20146607
TI  - Identifying the what, why, and how of an observed action: an fMRI study of
      mentalizing and mechanizing during action observation.
AB  - Humans commonly understand the unobservable mental states of others by observing
      their actions. Embodied simulation theories suggest that this ability may be
      based in areas of the fronto-parietal mirror neuron system, yet neuroimaging
      studies that explicitly investigate the human ability to draw mental state
      inferences point to the involvement of a &#x201C;mentalizing" system consisting
      of regions that do not overlap with the mirror neuron system. For the present
      study, we developed a novel action identification paradigm that allowed us to
      explicitly investigate the neural bases of mentalizing observed actions. Across
      repeated viewings of a set of ecologically valid video clips of ordinary human
      actions, we manipulated the extent to which participants identified the
      unobservable mental states of the actor (mentalizing) or the observable mechanics
      of their behavior (mechanizing). Although areas of the mirror neuron system did
      show an enhanced response during action identification, its activity was not
      significantly modulated by the extent to which the observers identified mental
      states. Instead, several regions of the mentalizing system, including dorsal and
      ventral aspects of medial pFC, posterior cingulate cortex, and temporal poles,
      were associated with mentalizing actions, whereas a single region in left lateral
      occipito-temporal cortex was associated with mechanizing actions. These data
      suggest that embodied simulation is insufficient to account for the sophisticated
      mentalizing that human beings are capable of while observing another and that a
      different system along the cortical midline and in anterior temporal cortex is
      involved in mentalizing an observed action.

PMID- 20146608
TI  - Time-dependent neural processing of auditory feedback during voice pitch error
      detection.
AB  - The neural responses to sensory consequences of a self-produced motor act are
      suppressed compared with those in response to a similar but externally generated
      stimulus. Previous studies in the somatosensory and auditory systems have shown
      that the motor-induced suppression of the sensory mechanisms is sensitive to
      delays between the motor act and the onset of the stimulus. The present study
      investigated time-dependent neural processing of auditory feedback in response to
      self-produced vocalizations. ERPs were recorded in response to normal and pitch
      shifted voice auditory feedback during active vocalization and passive listening
      to the playback of the same vocalizations. The pitch-shifted stimulus was
      delivered to the subjects' auditory feedback after a randomly chosen time delay
      between the vocal onset and the stimulus presentation. Results showed that the
      neural responses to delayed feedback perturbations were significantly larger than
      those in response to the pitch-shifted stimulus occurring at vocal onset. Active
      vocalization was shown to enhance neural responsiveness to feedback alterations
      only for nonzero delays compared with passive listening to the playback. These
      findings indicated that the neural mechanisms of auditory feedback processing are
      sensitive to timing between the vocal motor commands and the incoming auditory
      feedback. Time-dependent neural processing of auditory feedback may be an
      important feature of the audio-vocal integration system that helps to improve the
      feedback-based monitoring and control of voice structure through vocal error
      detection and correction.

PMID- 20146609
TI  - Failure to engage spatial working memory contributes to age-related declines in
      visuomotor learning.
AB  - It is well documented that both cognitive and motor learning abilities decline
      with normative aging. Given that cognitive processes such as working memory are
      engaged during the early stages of motor learning [Anguera, J., Reuter-Lorenz,
      P., Willingham, D., & Seidler, R. Contributions of spatial working memory to
      visuomotor learning. Journal of Cognitive Neuroscience, 22(9), 1917-1930, 2010],
      age-related declines in motor learning may be due in part to reductions in
      cognitive ability. The present study examined whether age-related declines in
      spatial working memory (SWM) contribute to deficits in visuomotor adaptation.
      Young and older adult participants performed a visuomotor adaptation task that
      involved adapting manual aiming movements to a 30 degrees  rotation of the visual
      feedback display as well as an SWM task in an fMRI scanner. Young adults showed a
      steeper learning curve than older adults during the early adaptation period. The
      rate of early adaptation was correlated with SWM performance for the young, but
      not older, adults. Both groups showed similar brain activation patterns for the
      SWM task, including engagement of the right dorsolateral prefrontal cortex and
      bilateral inferior parietal lobules. However, when the SWM activation was used as
      a limiting mask, younger adults showed neural activation that overlapped with the
      early adaptation period, whereas older adults did not. A partial correlation
      controlling for age revealed that the rate of early adaptation correlated with
      the amount of activation at the right dorsolateral prefrontal cortex. These
      findings suggest that a failure to effectively engage SWM processes during
      learning contributes to age-related deficits in visuomotor adaptation.

PMID- 20146610
TI  - Feedback-related negativity codes prediction error but not behavioral adjustment
      during probabilistic reversal learning.
AB  - We assessed electrophysiological activity over the medial frontal cortex (MFC)
      during outcome-based behavioral adjustment using a probabilistic reversal
      learning task. During recording, participants were presented two abstract visual
      patterns on each trial and had to select the stimulus rewarded on 80% of trials
      and to avoid the stimulus rewarded on 20% of trials. These contingencies were
      reversed frequently during the experiment. Previous EEG work has revealed
      feedback-locked electrophysiological responses over the MFC (feedback-related
      negativity; FRN), which correlate with the negative prediction error [Holroyd, C.
      B., & Coles, M. G. The neural basis of human error processing: Reinforcement
      learning, dopamine, and the error-related negativity. Psychological Review, 109,
      679-709, 2002] and which predict outcome-based adjustment of decision values
      [Cohen, M. X., & Ranganath, C. Reinforcement learning signals predict future
      decisions. Journal of Neuroscience, 27, 371-378, 2007]. Unlike previous
      paradigms, our paradigm enabled us to disentangle, on the one hand, mechanisms
      related to the reward prediction error, derived from reinforcement learning (RL)
      modeling, and on the other hand, mechanisms related to explicit rule-based
      adjustment of actual behavior. Our results demonstrate greater FRN amplitudes
      with greater RL model-derived prediction errors. Conversely expected negative
      outcomes that preceded rule-based behavioral reversal were not accompanied by an
      FRN. This pattern contrasted remarkably with that of the P3 amplitude, which was
      significantly greater for expected negative outcomes that preceded rule-based
      behavioral reversal than for unexpected negative outcomes that did not precede
      behavioral reversal. These data suggest that the FRN reflects prediction error
      and associated RL-based adjustment of decision values, whereas the P3 reflects
      adjustment of behavior on the basis of explicit rules.

PMID- 20146611
TI  - Two processes for recognition memory in children of early school age: an event
      related potential study.
AB  - We examined the ERP correlates of familiarity and recollection and their
      development in 8- to 10-year-old children and a control group of young adults.
      Capitalizing on the different temporal dynamics of familiarity and recollection,
      we tested recognition memory in both groups with a speeded and nonspeeded
      response condition. Consistent with the view that familiarity is available
      earlier than recollection and by this more relevant for speeded recognition
      judgments, adults and children showed an early frontal old/new effect, the
      putative ERP correlate of familiarity in the speeded response condition. No
      parietal old/new effect, the putative ERP correlate of recollection was obtained
      in the speeded condition in neither group. Conversely, in the nonspeeded
      condition, both groups showed the parietal old/new effect, and a frontal effect
      was additionally observed for adults. In light of the generally lower memory
      accuracy of the children, these data suggested that children use a weaker and
      less matured version of the same explicit memory network used by adults in which
      familiarity and recollection differentially contribute to speeded and nonspeeded
      recognition memory judgments.

PMID- 20146612
TI  - Is neocortical-hippocampal connectivity a better predictor of subsequent
      recollection than local increases in hippocampal activity? New insights on the
      role of priming.
AB  - During memory encoding, increased hippocampal activity-thought to reflect the
      binding of different types of information into unique episodes-has been shown to
      correlate with subsequent recollection of those episodes. Repetition priming
      thought to induce more efficient perceptual processing of stimuli-is normally
      associated with decreased neocortical activity and is often assumed to reduce
      encoding into episodic memory. Here, we used fMRI to compare activity to primed
      and unprimed auditory words in the presence of distracting sounds as a function
      of whether participants subsequently recollected the word-sound associations or
      only had a feeling of familiarity with the word in a subsequent surprise
      recognition task. At the behavioral level, priming increased the incidence of
      subsequent recollection. At the neuronal level, priming reduced activity in the
      superior temporal gyrus (STG) but also reversed the traditional increase in
      encoding-related hippocampal activity associated with subsequent recollection
      relative to subsequent familiarity. To explain this interaction pattern, further
      analyses using dynamic causal modeling showed an increase in connectivity from
      left STG to left hippocampus specific to words that were later recollected. These
      findings show that successful episodic encoding is not determined solely by local
      hippocampal activity and emphasize instead the importance of increased functional
      neocortical-hippocampal coupling. Such coupling might be a better predictor of
      subsequent recollection than the direction of local hippocampal changes per se.
      We propose that one consequence of priming is to "free up" attentional resources
      from processing an item in a noisy context, thereby allowing greater attention to
      encoding of that context.

PMID- 20146614
TI  - Steady-state signatures of visual perceptual load, multimodal distractor
      filtering, and neural competition.
AB  - The perceptual load theory of attention posits that attentional selection occurs
      early in processing when a task is perceptually demanding but occurs late in
      processing otherwise. We used a frequency-tagged steady-state evoked potential
      paradigm to investigate the modality specificity of perceptual load-induced
      distractor filtering and the nature of neural-competitive interactions between
      task and distractor stimuli. EEG data were recorded while participants monitored
      a stream of stimuli occurring in rapid serial visual presentation (RSVP) for the
      appearance of previously assigned targets. Perceptual load was manipulated by
      assigning targets that were identifiable by color alone (low load) or by the
      conjunction of color and orientation (high load). The RSVP task was performed
      alone and in the presence of task-irrelevant visual and auditory distractors. The
      RSVP stimuli, visual distractors, and auditory distractors were "tagged" by
      modulating each at a unique frequency (2.5, 8.5, and 40.0 Hz, respectively),
      which allowed each to be analyzed separately in the frequency domain. We report
      three important findings regarding the neural mechanisms of perceptual load.
      First, we replicated previous findings of within-modality distractor filtering
      and demonstrated a reduction in visual distractor signals with high perceptual
      load. Second, auditory steady-state distractor signals were unaffected by
      manipulations of visual perceptual load, consistent with the idea that perceptual
      load-induced distractor filtering is modality specific. Third, analysis of task
      related signals revealed that visual distractors competed with task stimuli for
      representation and that increased perceptual load appeared to resolve this
      competition in favor of the task stimulus.

PMID- 20146613
TI  - Language-universal sensory deficits in developmental dyslexia: English, Spanish,
      and Chinese.
AB  - Studies in sensory neuroscience reveal the critical importance of accurate
      sensory perception for cognitive development. There is considerable debate
      concerning the possible sensory correlates of phonological processing, the
      primary cognitive risk factor for developmental dyslexia. Across languages,
      children with dyslexia have a specific difficulty with the neural representation
      of the phonological structure of speech. The identification of a robust sensory
      marker of phonological difficulties would enable early identification of risk for
      developmental dyslexia and early targeted intervention. Here, we explore whether
      phonological processing difficulties are associated with difficulties in
      processing acoustic cues to speech rhythm. Speech rhythm is used across languages
      by infants to segment the speech stream into words and syllables. Early
      difficulties in perceiving auditory sensory cues to speech rhythm and prosody
      could lead developmentally to impairments in phonology. We compared matched
      samples of children with and without dyslexia, learning three very different
      spoken and written languages, English, Spanish, and Chinese. The key sensory cue
      measured was rate of onset of the amplitude envelope (rise time), known to be
      critical for the rhythmic timing of speech. Despite phonological and orthographic
      differences, for each language, rise time sensitivity was a significant predictor
      of phonological awareness, and rise time was the only consistent predictor of
      reading acquisition. The data support a language-universal theory of the neural
      basis of developmental dyslexia on the basis of rhythmic perception and syllable
      segmentation. They also suggest that novel remediation strategies on the basis of
      rhythm and music may offer benefits for phonological and linguistic development.

PMID- 20146615
TI  - Parametric manipulation of the conflict signal and control-state adaptation.
AB  - Mechanisms by which the brain monitors and modulates performance are an important
      focus of recent research. The conflict-monitoring hypothesis posits that the ACC
      detects conflict between competing response pathways which, in turn, signals for
      enhanced control. The N2, an ERP component that has been localized to ACC, has
      been observed after high conflict stimuli. As a candidate index of the conflict
      signal, the N2 would be expected to be sensitive to the degree of response
      conflict present, a factor that depends on both the features of external stimuli
      and the internal control state. In the present study, we sought to explore the
      relationship between N2 amplitude and these variables through use of a modified
      Eriksen flankers task in which target-distracter compatibility was parametrically
      varied. We hypothesized that greater target-distracter incompatibility would
      result in higher levels of response conflict, as indexed by both behavior and the
      N2 component. Consistent with this prediction, there were parametric degradations
      in behavioral performance and increases in N2 amplitudes with increasing
      incompatibility. Further, increasingly incompatible stimuli led to the predicted
      parametric increases in control on subsequent incompatible trials as evidenced by
      enhanced performance and reduced N2 amplitudes. These findings suggest that the
      N2 component and associated behavioral performance are finely sensitive to the
      degree of response conflict present and to the control adjustments that result
      from modulations in conflict.

PMID- 20146616
TI  - Putting the pieces together: the role of dorsolateral prefrontal cortex in
      relational memory encoding.
AB  - Results from fMRI have strongly supported the idea that the ventrolateral PFC
      (VLPFC) contributes to successful memory formation, but the role the dorsolateral
      PFC (DLPFC) in memory encoding is more controversial. Some findings suggest that
      the DLPFC is recruited when one is processing relationships between items in
      working memory, and this processing specifically promotes subsequent memory for
      these relationships. However, previous studies could not rule out the possibility
      that DLPFC promotes memory during all elaborative encoding conditions and
      contributes to memory on all subsequent associative memory tests. To address this
      question directly, we used fMRI to examine activity during two encoding tasks
      that prompted participants to encode either relational or item-specific
      information. On relational trials, participants imagined pairs of items
      interacting, whereas on item-specific trials, participants imagined the items
      spatially separated and in different sizes. After scanning, we examined memory
      for relational information and item-specific information. fMRI results showed
      that DLPFC activity specifically promoted memory for relational information
      during relational encoding and not memory for item-specific information during
      item-specific encoding. In contrast, activity in the VLPFC predicted memory for
      both relational and item-specific information. The present results are consistent
      with the idea that the DLPFC specifically contributes to successful memory
      formation through its role in building relationships among items.

PMID- 20146627
TI  - Does choice of combination antiretroviral therapy (cART) alter changes in
      cerebral function testing after 48 weeks in treatment-naive, HIV-1-infected
      individuals commencing cART? A randomized, controlled study.
AB  - BACKGROUND: Neurocognitive impairment remains prevalent, despite combination
      antiretroviral therapy (cART). Differences between changes in cerebral function
      and alternative cARTs have not been prospectively assessed. METHODS: Treatment
      naive, HIV-1-infected individuals randomly allocated to commence cART (tenofovir
      emtricitabine plus either efavirenz [arm 1], atazanavir-ritonavir [arm 2], or
      zidovudine-abacavir [arm 3]) were eligible. Cerebral function tests included
      neurocognitive testing and assessment of cerebral metabolites using proton
      magnetic resonance spectroscopy in several anatomical voxels, including right
      frontal white matter and right basal ganglia, at baseline and after 48 weeks. N
      acetylaspartate-to-creatine (NAA/Cr) ratios were calculated. Both the differences
      between changes in neurocognitive function and NAA/Cr ratios over 48 weeks and
      the study arms (arm 1 vs arm 2; arm 1 vs arm 3) were assessed. RESULTS: Thirty
      subjects completed study procedures (9, 9, and 12 subjects in arms 1, 2, and 3,
      respectively). Mean CD4+ cell counts (+/- standard deviation) were 218 +/- 87
      cells/microL at baseline and 342 +/- 145 cells/microL at week 48. The mean plasma
      HIV-1 RNA level was <50 copies/mL for 28 of the 30 subjects at week 48. Over 48
      weeks, greater improvements in identification reaction time (P = .04) and
      executive function (P = .02) were observed in arm 3, compared with arm 1 (0.03, 
      0.30, -0.50 log10 ms change in identification reaction time, in arms 1, 2, and 3,
      respectively). Increases in the NAA/Cr ratio were observed in all voxels (maximum
      38% in right basal ganglia), with greater increases observed in arm 1 than in arm
      2 (P = .03) in frontal white matter (30%, -7%, and 0% change in the NAA/Cr ratio,
      in arms 1, 2, and 3, respectively). CONCLUSIONS: To our knowledge, this is the
      first study to prospectively describe different changes in cerebral function
      testing parameters between different cARTs. Greater improvements in neuronal
      recovery (NAA/Cr ratio) were observed for recipients of tenofovir-emtricitabine
      plus efavirenz (arm 1), and greater improvements in neurocognitive function
      testing were observed for recipients of tenofovir-emtricitabine plus zidovudine
      abacavir (arm 3).

PMID- 20146628
TI  - Benefit or toxicity from neurologically targeted antiretroviral therapy?

PMID- 20146629
TI  - Outbreak of leptospirosis among Adventure Race participants in Florida, 2005.
AB  - BACKGROUND: On 21 November 2005, a 32-year-old male resident of New York was
      hospitalized with suspected leptospirosis. He had participated in an endurance
      length swamp race on 4-5 November 2005 outside of Tampa, Florida. METHODS: We
      interviewed racers to assess illness, medical care, and race activities. A
      suspected case was defined as fever plus > or = 2 signs or symptoms of
      leptospirosis occurring in a racer after 4 November 2005. Individuals with
      suspected cases were referred for treatment as needed and were asked to submit
      serum samples for microscopic agglutination testing (MAT) and for rapid testing
      by the dot enzyme-linked immunosorbent assay dipstick immunoglobulin M
      immunoassay. RESULTS: The Centers for Disease Control and Prevention and
      participating state health departments interviewed 192 (96%) of 200 racers from
      32 states and Canada. Forty-four (23%) of 192 racers met the definition for a
      suspected case. The median age of the patients was 37 years (range, 19-66 years),
      and 128 (66.7%) were male. Fourteen (45%) of the 31 patients with suspected cases
      who were tested had their cases confirmed by serological testing (a single sample
      with MAT titer > or = 400), including the index case patient. Organisms of a
      potential novel serovar (species Leptospira noguchii) were isolated in culture
      from 1 case patient. Factors associated with increased risk of leptospirosis
      included swallowing river water (odds ratio [OR], 3.4; 95% confidence interval
      [CI], 1.6-7.0), swallowing swamp water (OR, 2.4; 95% CI, 1.1-5.2), and being
      submerged in any water (OR, 2.3; 95% CI, 1.1-4.7). CONCLUSIONS: This report
      describes a leptospirosis outbreak that resulted in a high rate of symptomatic
      infection among adventure racers in Florida. The growing popularity of adventure
      sports may put more people at risk for leptospirosis, even in areas that have not
      previously been considered areas of leptospirosis endemicity.

PMID- 20146630
TI  - Intravenous and inhalational colistin-induced respiratory failure.
AB  - The emergence of highly resistant gram-negative pathogens in hospitals around the
      world has placed emphasis on colistin, a seemingly ancient drug. Respiratory
      failure from colistin was reported in the years following its release; however,
      there are no recent reports of colistin-induced respiratory failure. We report a
      case of intravenous colistin- and, later, inhalational colistin-induced
      respiratory failure.

PMID- 20146632
TI  - Toll-like receptors as therapeutic targets in gastrointestinal diseases.
AB  - IMPORTANCE OF THE FIELD: Toll-like receptors (TLRs) are innate immunity receptors
      that recognize several different antigens, initiating immunological/inflammatory
      responses. Recent evidence associates numerous pathophysiological processes and
      diseases with dysregulated activation of these receptors, conferring a potential
      therapeutic value to their modulation. AREAS COVERED IN THIS REVIEW: The aim of
      this systematic review that covers literature from the past 10 years is to
      address the role of TLRs in the pathophysiology of gastrointestinal (GI) diseases
      as well as the therapeutic potential of modulating TLRs' signaling pathways in GI
      pathology. WHAT THE READER WILL GAIN: This review shows that TLRs play an
      important role in the pathophysiology of several GI diseases and that modulating
      TLRs signaling pathways may have an enormous therapeutic potential. Different
      methods for modulation of TLRs' activity in GI tract, with direct
      agonists/antagonists but also with non-specific substances, like antibiotics or
      probiotics, are presented. TAKE HOME MESSAGE: Even though TLRs modulators have
      been used for therapy in some GI diseases, further research, particularly in
      humans, is needed in order to establish the precise role of the different TLRs in
      the diverse GI diseases and to motivate clinical trials that consider TLRs as
      therapeutic targets in GI pathology.

PMID- 20146633
TI  - PAK as a therapeutic target in gastric cancer.
AB  - IMPORTANCE OF THE FIELD: Gastric cancer is one of the most common causes of
      cancer death worldwide. P21-activated kinases (PAKs), regulators of cancer-cell
      signalling networks, play fundamental roles in a range of cellular processes
      through their binding partners or kinase substrates. AREAS COVERED IN THIS
      REVIEW: The complex regulation of PAKs through their upstream or downstream
      effectors in human cancers, especially in gastric cancer, are described and the
      identified inhibitors of PAKs are summarized. WHAT THE READERS WILL GAIN: The
      structural differences and activation mechanisms between two subgroups of PAK are
      described. Both groups of PAKs play complicated and important roles in human
      gastric cancer, which indicated a possible way for us to identify the specific
      inhibitors targeting PAKs for gastric cancer. TAKE HOME MESSAGE: PAKs play
      important roles in progression of many cancer types, the full mechanisms of PAKs
      in gastric cancer are still unclear. It seems there are different roles for two
      groups of PAKs in cancers. Group I PAKs play their functions mostly through their
      specific substrates, however, many binding partners that are independent of
      phosphorylation by group II PAKs were identified. Finding specific inhibitors of
      PAKs will help us discover the roles of PAKs and target these kinases in human
      gastric cancer.

PMID- 20146631
TI  - Activity of elvitegravir, a once-daily integrase inhibitor, against resistant HIV
      Type 1: results of a phase 2, randomized, controlled, dose-ranging clinical
      trial.
AB  - BACKGROUND: This phase 2, randomized, active-controlled, 48-week study assessed
      the noninferiority of the human immunodeficiency virus (HIV) integrase inhibitor
      elvitegravir to comparator ritonavir-boosted protease inhibitor (CPI/r) in
      treatment-experienced subjects. METHODS: Subjects had HIV RNA levels 1000
      copies/mL and 1 protease resistance mutation. Subjects received nucleoside or
      nucleotide reverse-transcriptase inhibitors (NRTIs) with or without T-20 and
      either CPI/r or once-daily elvitegravir at a dose of 20 mg, 50 mg, or 125 mg
      (blinded to dose) with ritonavir. After week 8, the independent data monitoring
      committee stopped the elvitegravir 20 mg arm and allowed subjects in the
      elvitegravir 50 mg and 125 mg arms to add protease inhibitors. The primary end
      point was the time-weighted average change from baseline in HIV RNA level through
      week 24 (DAVG(24)). RESULTS: A total of 278 subjects with a median of 11 protease
      and 3 thymidine analog mutations were randomized and treated. One-half of
      subjects received NRTIs without expected antiviral activity. Compared with the
      DAVG(24) for the CPI/r arm (-1.19 log(10) copies/mL), the elvitegravir 50 mg arm
      was noninferior (-1.44 log(10) copies/mL), and the elvitegravir 125 mg arm was
      superior (-1.66 log(10) copies/mL; P = .021). Efficacy was impacted by activity
      of background agents. There was no relationship between elvitegravir dosage and
      adverse events. CONCLUSIONS: Elvitegravir was well-tolerated and produced rapid
      virologic suppression that was durable with active background therapy. Trial
      registration. ClinicalTrials.gov identifier number: NCT00298350.

PMID- 20146634
TI  - T cell receptor (TCR) gene therapy to treat melanoma: lessons from clinical and
      preclinical studies.
AB  - IMPORTANCE OF THE FIELD: Adoptive T cell therapy (ACT) with tumour infiltrating
      lymphocytes is currently the best treatment option for metastatic melanoma.
      Despite its clinical successes, ACT has limitations in availability and
      generation of therapeutic T cells for a larger group of patients. Introduction of
      tumour-specific T cell receptors into T cells, termed TCR gene therapy, can
      provide an alternative for ACT that is more widely applicable and might be
      extended to other types of cancer. AREAS COVERED IN THIS REVIEW: The current
      status of TCR gene therapy studies including clinical challenges, such as on
      target toxicity, compromised anti-tumour T cell responses, compromised T cell
      persistence and potential immunogenicity of receptor transgenes. Strategies to
      address these challenges are covered. WHAT THE READER WILL GAIN: A listing and
      discussion of strategies that aim at improving the efficacy and safety of TCR
      gene therapy. Such strategies address antigen choice, TCR mis-pairing, functional
      avidity and persistence of T cells, immune responses towards receptor transgenes,
      and combination of ACT with other therapies. TAKE HOME MESSAGE: To ensure further
      clinical development of TCR gene therapy, it is necessary to choose safe T cell
      target antigens, and implement (combinations of) strategies that enhance the
      correct pairing of TCR transgenes and the functional avidity and persistence of T
      cells.

PMID- 20146635
TI  - Spermatogonial stem cells, in vivo transdifferentiation and human regenerative
      medicine.
AB  - IMPORTANCE OF THE FIELD: Embryonic stem (ES) cells have potential for use in
      regenerative medicine, but use of these cells is hindered by moral, legal and
      ethical issues. Induced pluripotent cells have promise in regenerative medicine.
      However, since generation of these cells involves genetic manipulation, it also
      faces significant hurdles before clinical use. This review discusses
      spermatogonial stem cells (SSCs) as a potential alternative source of pluripotent
      cells for use in human regenerative medicine. AREAS COVERED IN THE REVIEW: The
      potential of SSCs to give rise to a wide range of other cell types either
      directly, when recombined with instructive inducers, or indirectly, after being
      converted to ES-like cells. Current understanding of the differentiation
      potential of murine SSCs and recent progress in isolating and culturing human
      SSCs and demonstrating their properties is also discussed. WHAT THE READER WILL
      GAIN: Insight into the plasticity of SSCs and the unique properties of these
      cells for regenerative applications, the limitations of SSCs for stem-cell-based
      therapy and the potential alternatives available. TAKE HOME MESSAGE: If
      methodologies for isolation and conversion of adult human SSCs directly into
      other cell types can be effectively developed, SSCs could represent an important
      alternate source of pluripotent cells that can be used in human tissue repair
      and/or regeneration.

PMID- 20146636
TI  - Are biosimilars really generics?
AB  - IMPORTANCE OF THE FIELD: Ever since the formation of the first biotechnology
      company almost three decades ago, more than 150 biopharmaceutical products have
      been marketed across the globe. The oldest of these biotechnology-derived
      products are now at the end of their patent lives, as a result of which, the
      development of 'biosimilars' is increasing. AREAS COVERED IN THE REVIEW: The
      review highlights aspects in which biosimilars differ from generic drugs. WHAT
      THE READER WILL GAIN: The active substance of a biosimilar medicine is similar to
      the one of the biological reference medicine; however, biosimilars differ from
      generics of pharmacological drugs in aspects like size and complexity of the
      active substance, and the nature of the manufacturing process. The manufacture of
      a biopharmaceutical product is complex and involves several isolation and
      purification steps. These procedures are proprietary to the manufacturer of the
      originator product and hence even minor changes in production can have serious
      implications in terms of safety and efficacy of the product. TAKE HOME MESSAGE:
      Biosimilars should not be brought to market using the same procedure applied to
      generics, and existing and future regulation should prevent inappropriate and
      automatic substitution of a biosimilar for a reference biopharmaceutical product.

PMID- 20146637
TI  - Vitamin E prevents steroid-induced osteonecrosis in rabbits.
AB  - BACKGROUND AND PURPOSE: Prevention of osteonecrosis after corticosteroid
      administration would be important. We examined the potential of vitamin E (alpha
      tocopherol) to reduce the incidence of corticosteroid-induced osteonecrosis in an
      animal model. METHODS: Japanese white rabbits were divided into 2 groups; the
      control group was fed a normal diet and the experimental group was fed alpha
      tocopherol-supplemented diet in which alpha-tocopherol (600 mg/kg diet) was added
      to the normal diet. To induce osteonecrosis, high-dose methylprednisolone acetate
      (MPSL) (20 mg/kg body weight) was injected once into the right gluteus medius
      muscle of all rabbits. 4 weeks after the injection of MPSL, the presence or
      absence of osteonecrosis of bilateral femurs was examined histopathologically.
      The tocopherol/cholesterol ratios were calculated. The plasma levels of
      thiobarbituric acid-reactive substances (TBARS) were measured. RESULTS: Alpha
      tocopherol-supplemented diet reduced the incidence of osteonecrosis, which
      developed in 14 of 20 rabbits in the control group and 5 of 21 rabbits in the
      experimental group (p = 0.004). The tocopherol/cholesterol ratio was higher in
      the experimental group than in the control group after the alpha-tocopherol
      administration. The plasma TBARS level was lower in the experimental group than
      in the control group at 4 weeks after the MPSL administration. INTERPRETATION:
      Our findings may offer a new approach for the prevention of corticosteroid
      induced osteonecrosis.

PMID- 20146638
TI  - Can orthopedic trials change practice?
AB  - BACKGROUND AND PURPOSE: The impact of large, randomized trials in orthopedic
      surgery on surgeons' preferences for a particular surgical approach remains
      unclear. We surveyed surgeons to assess whether they would change practice based
      upon results of a large, multicenter randomized controlled hip fracture trial.
      METHODS: We conducted a cross-sectional survey among International Hip Fracture
      Research Collaborative (IHFRC) surgeons and surgeons who were members of
      Arbeitsgemeinschaft fuer Osteosynthesefragen - Association for the Study of
      Internal Fixation (AO/ASIF) to determine the likelihood that they would change
      practice based on findings of a proposed large, multicenter randomized controlled
      trial (the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty
      versus Hemi-Arthroplasty (HEALTH) study). We asked surgeons their current
      preferences for the management of displaced femoral neck fractures and whether a
      trial that definitively revealed a substantial improvement in function and
      quality of life with no difference in risk of revision surgery was important and
      would cause them to change practice. RESULTS: Of 883 surgeons surveyed, 210
      responded from IHFRC and 586 from AO/ASIF (a response rate of 90%). Most surgeons
      (61%) preferred hemiarthroplasty (HA) for treating displaced femoral neck
      fractures. 72% of responding surgeons believed that a substantial improvement in
      patient function with total hip arthroplasty (THA) and no adverse effects on
      revision surgery would be an important finding. Moreover, of 483 surgeons who
      preferred hemiarthroplasty, 62% would change their practice based upon the
      findings of the trial. INTERPRETATION: Large clinical trials in orthopedics are
      worthwhile endeavors, as they have the potential to change practice among
      surgeons. Surgeons seem willing to adopt alternative surgical approaches if the
      evidence is compelling and sound.

PMID- 20146639
TI  - A stature-specific concept for uncemented, primary total hip arthroplasty.
AB  - BACKGROUND AND PURPOSE: Variations in hip anatomy limit the femoral canal fit of
      standard uncemented hip stems. In addition, there are still issues with leg
      length discrepancy and offset reconstruction, potentially resulting in
      impingement, dislocation, and wear. Modular stems with different shapes for
      femoral canal fit and multiple neck options may improve the outcome and reduce
      complications. PATIENTS AND METHODS: 173 patients (190 hips) received an
      uncemented THA with 1 of 2 different stem shapes for canal fit and a modular neck
      for stature-specific hip reconstruction. Median follow-up time was 9 (7-13)
      years. During the follow-up period, 20 patients died (22 hips) and 12 patients
      (13 hips) were lost to follow-up. 155 hips were available for evaluation,
      including clinical and radiological outcome. RESULTS: 1 stem was revised for a
      periprosthetic fracture following trauma; 10 cups and 2 modular necks were
      revised (1 for breakage and 1 during cup revision). At 10 years, stem survival
      was 100%, modular neck survival was 99% (CI: 95-100), and cup survival was 94%
      (CI: 87-97). No leg length discrepancies were measured in 96% of cases. Offset
      with anatomic lateralization was achieved in 98%. Median Harris hip score was 94
      (47-100) and median Merle d'Aubigne score was 16 (10-18). Relevant radiolucent
      lines and osteolysis were not found. INTERPRETATION: The uncemented modular neck,
      dual-stem system used in this series allows accurate reconstruction of the joint
      by adapting the implant to the needs of the patient. This may improve the outcome
      of primary THA, which is supported by the results of this medium-term follow-up
      evaluation.

PMID- 20146640
TI  - The impact of premenstrual symptoms on activities of daily life in Korean women.
AB  - OBJECTIVE: To evaluate the impact of premenstrual symptoms on activities of daily
      life (ADL) of Korean women, and their knowledge and treatment seeking regarding
      premenstrual syndromes (PMSs). METHODS: A population-based online survey
      regarding premenstrual symptoms was conducted in 1000 Korean women aged 15-49
      years. Symptoms were classified according to their intensity, persistence each
      cycle, and impairment of ADL. Women's knowledge of PMSs and physician
      consultations were assessed. RESULTS: The approximate prevalence of
      PMS/premenstrual dysphoric disorder (PMDD) by the WHO's International
      Classification of Disease (ICD-10), American College of Obstetrics and Gynecology
      (ACOG), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV[4th
      edition]) criteria was 98.6, 32.1, and 2.8%, respectively. Among 23 documented
      symptoms, the most predominant symptoms were joint-muscle-back pain, abdominal
      pain, and irritability. Physical symptoms were more prevalent than mental
      symptoms. There was a high correlation between the duration and severity of
      symptoms. The impact of PMS on ADL and the proportion of women with impaired ADL
      were significantly associated with the severity of PMS. The proportion of women
      consulting physicians increased with severity of PMS from 2%, 2.3%, for ICD-10,
      ACOG PMS to 10.7% for DSM-IV PMDD, respectively. Most of the women (91.5%) had no
      knowledge regarding terminology pertaining to PMS and PMDD. CONCLUSION: PMSs
      occur frequently and have a significant impact on daily life for a proportion of
      Korean women. However, Korean women have little knowledge about PMSs and only
      infrequently consult their physicians.

PMID- 20146641
TI  - Pre-birth characteristics and 5-year follow-up of women with cryopreserved
      embryos after successful in vitro fertilisation treatment.
AB  - Many patients do not make a decision about the disposition of their surplus
      embryos until they are compelled to do so by statutory limits. In the current
      study, the characteristics of women who had conceived through in vitro
      fertilisation (IVF) and who still had embryos stored (E-S; n = 26) 5 years after
      IVF were compared to a cohort comparison group (C-C; n = 40). At time 1 (T1, 28
      weeks pregnant) women completed questionnaires on personality traits (anxiety,
      locus of control and dependency) and participated in an interview on socio
      demographic characteristics, family composition and stored embryos. At T2 (5
      years later) women were re-interviewed and asked about beliefs about the embryos.
      Women in the E-S group were significantly younger, had been married or living
      with their partner for fewer years and had had more children than the C-C group.
      Further, women in the E-S group were more likely to have an external locus of
      control and a dependent personality than women in the C-C group. Almost all women
      in the E-S group (88.5%) thought of their embryos as siblings to existing
      children, and reported thinking about the embryos occasionally (61.5%) or
      frequently (34.6%). The personality differences identified may suggest that women
      who still have embryos after the end of fertility treatment may be in need of
      decision support.

PMID- 20146642
TI  - Measuring posttraumatic stress following childbirth: a critical evaluation of
      instruments.
AB  - OBJECTIVES: To evaluate instruments used to assess posttraumatic stress disorder
      (PTSD) following childbirth with both quantitative (reliability analysis and
      factor analysis) and qualitative (comparison of operationalization) techniques.
      METHODS: An unselected population of 428 women completed the Traumatic Event
      Scale-B (TES-B) and the PTSD Symptom Scale-Self Report (PSS-SR) 2-6 months after
      delivery. RESULTS: Assessment of internal consistency yielded similar results for
      the TES-B and PSS-SR (Cronbach's alpha = 0.87 and 0.82, respectively). Factor
      analysis revealed two rather than three DSM-IV symptom categories for both
      instruments: childbirth-related factors (re-experiencing/ avoidance) and symptoms
      of depression and anxiety (numbing/hyperarousal). Although the TES-B and the PSS
      SR sum-scores show a strong relationship (Spearmans rho = 0.78), agreement
      between the instruments on the identification of PTSD cases is low (kappa =
      0.24); discrepancy between TES-B and PSS-SR is largely due to differences in
      instruction to respondents, formulation of items, answer categories, and cut-off
      values. CONCLUSIONS: Large operationalization differences between TES-B and PSS
      SR have been identified, i.e., in the formulation of questions, answer
      categories, cut-off values and instructions to respondents. Comparison between
      studies using different instruments for measuring PTSD following childbirth
      should be done with utmost caution.

PMID- 20146643
TI  - How to diagnose cardiac amyloidosis early: impact of ECG, tissue Doppler
      echocardiography, and myocardial biopsy.
AB  - AIMS: To detect cardiac amyloidosis (CA) earlier, it is inevitable to improve
      diagnostic strategies. METHODS AND RESULTS: The impact of ECG, echocardiography
      including tissue Doppler imaging (TDI) and strain, and myocardial biopsies was
      evaluated in 30 patients (63% (n = 19) men, mean age 66 +/- 8 years, NYHA 3.0 +/-
      0.5, 73% with prior myocardial decompensation), in whom we proved CA. Amyloid was
      confirmed by apple-green birefringence under polarised light, and the causing
      protein by immunohistochemical examinations. Genetic analyses excluded familial
      CA. All patients (AL-lambda (n = 22), AL-kappa (n = 3), senile amyloidosis (n =
      5)) had echocardiographic signs of restrictive cardiomyopathy (RCM), typical TDI
      and strain parameters (E'septal; E' lateral < 8 cm/s; E/E' > 8; S' < or =9 cm/s;
      global longitudinal strain (GLS) -7.9 +/- 3.8%). Pericardial effusions were
      present in 63% of patients. ECGs were suspicious in many patients: 19 (63%) had
      low-voltage, 23 (77%) reduced R waves in V(1)-V(4), and 57% both. Abnormalities,
      retrospectively had been present for 0.5-4 years. Twenty (67%) patients died 232
      +/- 268 [2-1020] days after CA was diagnosed, but 502 +/- 333 [30-1440] days
      after the first symptom. CONCLUSION: Accurate ECG evaluations, careful
      echocardiographic search for RCM, reduced strain/strain rates, and general
      indications to myocardial biopsies with correct analyses are needed to diagnose
      CA.

PMID- 20146644
TI  - ALkappa(I) (UNK) - primary structure of an AL-amyloid protein presenting an organ
      limited subcutaneous nodular amyloid syndrome of long duration. Case report and
      review.
AB  - Slowly progressing subcutaneous nodules all over the body were detected in 1994
      in an otherwise healthy, now 66-year-old woman (UNK). A first biopsy was taken 10
      years ago and revealed amyloid. Immunohistochemistry was suggestive for ALkappa.
      From a nodular excisate, performed in the same year for cosmetic reasons, amyloid
      fibrils were extracted. Protein separation according to their size revealed
      multiple protein fragments below the MW of an intact kappa-light chain. They were
      identified as kappa-fragments by Western blotting. The kappa-fragments were
      cleaved into overlapping peptides using tryptic, N-Asp and chymotryptic digests.
      Peptides were sequenced by Edman-degradation and mass spectrometry. The complete
      amino acid sequence of the variable region and most of the constant region of
      ALkappa (UNK) was identified in various fragments comprising positions 1 to 207
      of a monoclonal kappa(I)-light chain. Four novel and several rare amino acid
      exchanges have been identified as compared to 17 amyloidogenic and >100 non
      amyloidogenic kappa(I)-sequences published, leading to increased hydrophobicity
      of ALkappa (UNK). Sequence analysis of C-region peptides allowed one to determine
      the kappa-allotype as being invb(+). A rabbit antibody was produced against
      ALkappa(I) (UNK). It strongly reacted with amyloid on formalin-fixed paraffin
      embedded tissue sections of the same patient and detected ALkappa-amyloid of many
      other patients. In contrast, antibodies produced against kappaBJP of subclasses
      kappa(I)-kappa(IV) failed to label ALkappa (UNK) amyloid deposits. The patient
      continues to be free of systemic disease, already for 14 years until today.

PMID- 20146645
TI  - Exceptional oral manifestations of amyloid light chain protein (AL) systemic
      amyloidosis.
AB  - Oral amyloidosis is usually presented in the tongue and is often associated with
      multiple myeloma. We present three patients with unusual oral manifestations of
      primary amyloidosis, which to the best of our knowledge have not been previously
      published. In two cases the oral manifestation was overt at the time of diagnosis
      and all cases ended in patient mortality. Since these oral manifestations can
      contribute to the diagnosis of systemic amyloidosis, clinicians should be made
      aware of them. Future research should assess the significance of oral
      manifestation as a prognostic indicator.

PMID- 20146646
TI  - Strengthening the positions of Scandinavian science in research on
      neurodegenerative and age-dependent amyloid diseases.

PMID- 20146647
TI  - Depressive disorder.

PMID- 20146648
TI  - WFSBP Guidelines on Brain Stimulation Treatments in Psychiatry.

PMID- 20146649
TI  - Longitudinal analysis of the suicidal behaviour risk in short-term placebo
      controlled studies of mirtazapine in major depressive disorder.
AB  - OBJECTIVE: To examine suicidal behaviour risk in the short-term placebo
      controlled studies of mirtazapine in Major Depressive Disorder (MDD). METHOD:
      Longitudinal Generalized Estimating Equations analyses were performed on pooled
      data from 15 placebo-controlled, randomized, double-blind, short-term trials of
      mirtazapine, using the suicide item scores from the Hamilton Depression Rating
      Scale (HAMD) as a proxy outcome measure for suicidality risk. RESULTS: The
      overall analysis using the convention that a patient is at risk if the HAMD
      suicide item score is > or =3, and excluding patients at risk at baseline,
      demonstrated a statistically significantly lower risk for mirtazapine- compared
      to placebo-treated patients on the HAMD (odds ratio mirtazapine versus placebo
      0.38; 95% confidence interval 0.21-0.66; P= 0.0008). CONCLUSION: Our results
      based on pooled data from 15 placebo-controlled, short-term studies of
      mirtazapine in MDD using the suicide item scores from the HAMD as a proxy outcome
      measure for suicidality risk, demonstrate that mirtazapine was associated with
      statistically significantly lower suicidality risk compared to placebo.

PMID- 20146650
TI  - Association analysis between gene variants of the tyrosine hydroxylase and the
      serotonin transporter in borderline personality disorder.
AB  - OBJECTIVES: For patients with borderline personality disorder (BPD), we
      previously reported an independent effect of the catechol-o-methyl-transferase
      (COMT) low-activity (Met(158)) allele and an interaction with the low-expression
      allele of the deletion/insertion (short/long or S/L, resp.) polymorphism in the
      serotonin transporter-linked promoter region (5-HTTLPR). The purpose of the
      present study was to extend these findings to the tyrosine hydroxylase (TH)
      Val(81)Met single nucleotide polymorphism (SNP), the 5-HTTLPR S/L polymorphism
      incorporating the recently described functional A/G SNP within the long allele of
      the 5-HTTLPR (rs25531) as well as the variable number of tandem repeat (VNTR)
      polymorphism within intron 2 of the serotonin transporter gene (STin2). METHODS:
      In 156 Caucasian BPD patients and 152 healthy controls, we tested for association
      between BPD and the TH Val(81)Met SNP, the 5-HTTLPR/rs25531 polymorphism, the
      STin2, the interaction of the TH Val(81)Met SNP with the tri-allelic 5
      HTTLPR/rs25531, the interaction of the TH Val(81)Met SNP with STin2. RESULTS:
      Between BPD patients and controls, we observed a slight over-representation of
      the TH Met(81)Met genotype in BPD patients compared to controls, but no
      statistically significant differences in genotype distribution of the individual
      markers after adjusting for multiple testing. Logistic regression analysis showed
      a lack of interaction between the TH Val(81)Met and the 5-HTTLPR/rs25531 as well
      as between the TH Val(81)Met and the STin2 polymorphism. CONCLUSIONS: These data
      do not suggest independent or interactive effects of the TH Val(81)Met, the 5
      HTTLPR/rs25531, or the STin2 polymorphisms in BPD.

PMID- 20146651
TI  - Insertion/deletion polymorphism in the gene for angiotensin converting enzyme
      (ACE) in panic disorder: A gender-specific effect?
AB  - Family, twin, and segregation analytic studies indicate a complex genetic
      contribution to panic disorder with an estimated heritability of 48%. Angiotensin
      converting enzyme (ACE) degrades substance P, which has been implicated in
      anxiety-related behaviour. ACE has been suggested as a potential risk factor in
      the pathogenesis of panic attacks. A functional insertion deletion (I/D)
      polymorphism in the ACE gene was suggested to be associated with panic disorder
      in a potentially gender-specific way ( Olsson et al. 2004 ). The present study
      aimed to replicate this finding and thereby to further elucidate the role of ACE
      gene variation in the pathomechanism of panic disorder. The ACE I/D polymorphism
      was genotyped in a sample of 102 German patients with panic disorder with or
      without agoraphobia as well as a healthy German control group matched with regard
      to age and sex (n = 102). In the male subgroup (n = 43) of panic patients a
      significant association of the ACE I allele (P = 0.0474) and genotypes containing
      the I allele (P = 0.0195), respectively, was observed. The present results
      provide further support for a potentially male-specific role of the less active
      ACE I allele in the pathogenesis of panic disorder, possibly by altering
      substance P levels.

PMID- 20146653
TI  - Abnormal body perception and neural activity in the insula in depression: an fMRI
      study of the depressed "material me".
AB  - OBJECTIVES: In addition to affective-cognitive symptoms, patients with major
      depressive disorder (MDD) suffer from somato-vegetative symptoms, suggesting
      abnormal interoceptive awareness of their "material me". While recent imaging
      studies have extensively investigated affective-cognitive symptoms in MDD, the
      neural correlates of somato-vegetative symptoms and abnormal interoception remain
      unclear. Since the "material me" has been especially associated with the anterior
      insula in healthy subjects, we hypothesized abnormalities in this region during
      interoceptive awareness in MDD. METHODS: We therefore investigated behavioural
      and neural correlates of interoception in healthy and depressed subjects using
      the Body Perception Questionnaire (BPQ) and a well established heartbeat
      perception task in fMRI. RESULTS: MDD patients showed significantly higher scores
      in the BPQ and reduced neural activity during rest periods, particularly in the
      bilateral anterior insula. In contrast to healthy subjects, BPQ scores no longer
      correlated with activity during rest periods in the anterior insula. Both BPQ
      scores and left anterior insula signal changes correlated with depression
      severity. CONCLUSIONS: We demonstrate for the first time abnormal body perception
      and altered activity in the insula during rest in MDD. Our results suggest that
      these behavioural and neural abnormalities are closely related to these patients'
      somato-vegetative abnormalities and their abnormal "material me".

PMID- 20146654
TI  - The role of clinical guidelines in patient care: thyroid hormone replacement in
      women of reproductive age.
AB  - BACKGROUND: Clinical guidelines have a role in medical education and in the
      standardization of patient care. However, it is not clear whether guidelines
      created by subspecialists reach relevant practicing physicians or influence
      patient care. In 2007 the Endocrine Society released "Guidelines on the
      Management of Thyroid Dysfunction During Pregnancy and Postpartum." The objective
      of this study was to characterize the role of these guidelines in provider
      education and in subsequent patient care decisions. METHOD: In 2009 three waves
      of mail surveys were distributed to 1601 Wisconsin health care providers with a
      history of providing obstetric care. Survey participants were members of the
      American College of Obstetricians and Gynecologists or the American Academy of
      Family Physicians. There were 881 returned surveys (55%) and 575 were eligible
      for the study (adjusted rate 52.5%). RESULTS: Although only 11.5% of providers
      read the Endocrine Society's guidelines, reading the guidelines was associated
      with increased likelihood of prepregnancy counseling on levothyroxine management
      (p < 0.0001), increased likelihood of screening for thyroid disease risk factors
      (p = 0.0007), and increased likelihood of empiric levothyroxine dose increase in
      pregnant patients (p = 0.0005). After controlling for provider sex, membership
      affiliation, practice setting, and number of years in practice, reading the
      guidelines was still an independent predictor of patient education prepregnancy
      (p < 0.01). CONCLUSION: The Endocrine Society's "Guidelines on the Management of
      Thyroid Dysfunction During Pregnancy and Postpartum" reached a minority of
      providers involved in obstetrics, but exposure to the guidelines did impact
      patient care. A multidisciplinary approach to guideline creation would improve
      the dissemination and practical application of guidelines.

PMID- 20146655
TI  - Thyroid storm with multiorgan failure.
AB  - BACKGROUND: Thyroid storm is a rare and potentially fatal condition. Various
      unusual presentations in patients with thyroid storm have been described but
      multiorgan dysfunction is uncommonly seen. SUMMARY: We describe a 35-year-old
      patient with a history of Graves' disease who was diagnosed with thyroid storm at
      2 weeks postpartum. This was complicated by acute liver failure, acute kidney
      injury, severe lactic acidosis, disseminated intravascular coagulation, and heart
      failure with acute pulmonary edema. The multiorgan dysfunction was reversed by
      prompt institution of antithyroid drugs and supportive management in the
      intensive care unit. CONCLUSION: Thyroid storm is a medical emergency. One of the
      challenges lies in recognizing its varied presentations. Early diagnosis and
      appropriate treatment is important to prevent the catastrophic outcomes
      associated with this condition.

PMID- 20146656
TI  - Hyperthyroidism caused by a germline activating mutation of the thyrotropin
      receptor gene: difficulties in diagnosis and therapy.
AB  - BACKGROUND: Germline activating mutations of the thyrotropin receptor (TSHR) gene
      have been considered as the only known cause of sporadic nonautoimmune
      hyperthyroidism in the pediatric population. Here we describe the long-term
      follow-up and evaluation of a patient with sporadic nonautoimmune primary
      hyperthyroidism who was found to have a de novo germline activating mutation of
      the TSHR gene. SUMMARY: The patient was an infant who presented at the age of 10
      months in an unconscious state with exsiccation, wet skin, fever, and
      tachycardia. Nonautoimmune primary hyperthyroidism was diagnosed, and brain
      magnetic resonance imaging and computed tomography showed also Arnold-Chiari
      malformation type I. Continuous propylthiouracil treatment resulted in a
      prolonged clinical cure lasting for 10 years. At the age of 11 years and 5 months
      the patient underwent subtotal thyroidectomy because of symptoms of trachea
      compression caused by a progressive multinodular goiter. However, 2 months after
      surgery, hormonal evaluation indicated recurrent hyperthyroidism and the patient
      was treated with propylthiouracil during the next 4 years. At the age of 15 years
      the patient again developed symptoms of trachea compression. Radioiodine
      treatment resulted in a regression of the recurrent goiter and a permanent cure
      of hyperthyroidism without relapse during the last 3 years of his follow-up.
      Sequencing of exon 10 of the TSHR gene showed a de novo heterozygous germline
      I630L mutation, which has been previously described as activating mutation at
      somatic level in toxic thyroid nodules. CONCLUSIONS: The I630L mutation of the
      TSHR gene occurs not only at somatic level in toxic thyroid nodules, but also its
      presence in germline is associated with nonautoimmune primary hyperthyroidism.
      Our case report demonstrates that in this disorder a continuous growth of the
      thyroid occurs without any evidence of elevated TSH due to antithyroid drug
      overdosing. This may justify previous recommendations for early treatment of
      affected patients with removal of as much thyroid tissue as possible.

PMID- 20146657
TI  - Eye and eyelid abnormalities are common in patients with Hashimoto's thyroiditis.
AB  - BACKGROUND: Overt ophthalmopathy is presumed to be uncommon in patients with
      Hashimoto's thyroiditis compared to Graves' disease, where significant eye
      changes are found in approximately 40% of patients. On the other hand, when
      observing, more subtle eye changes, particularly upper eyelid retraction (UER)
      and mild inflammatory signs, may be common in patients with Hashimoto's
      thyroiditis. METHODS: We have determined the prevalence and characteristics of
      eye signs in recently diagnosed patients with Hashimoto's thyroiditis studied
      prospectively since 2004 till date in Sydney (Australia). We measured serum
      orbital antibodies in 20 of the patients in enzyme-linked immunosorbent assay.
      RESULTS: The overall prevalence of eye signs in patients with Hashimoto's
      thyroiditis was 34%, of whom about a quarter had chronic UER, determined as a
      margin-reflex distance of >5 mm, as the main sign. There was no correlation
      between eye signs and cigarette smoking. Overall, there was only a modest
      correlation between eye signs and positive antibody tests, and 40% of patients
      with no eye signs at the time of study were antibody positive. CONCLUSION: Eye
      changes, in particular UER, are common in patients with Hashimoto's thyroiditis.
      Since thyroid stimulating hormone-receptor antibodies are not usually associated
      with Hashimoto's thyroiditis, autoimmune mediated damage of the levator palpebrae
      superioris (eyelid) muscle cannot be due to these antibodies. Although eyelid
      abnormalities may be a minor problem for most patients, for some there are major
      cosmetic implications requiring surgical management.

PMID- 20146658
TI  - Metabolic parameters and perinatal outcomes of gestational diabetes mellitus in
      women with polycystic ovary syndrome.
AB  - AIMS: To investigate metabolic characteristics and perinatal outcomes of
      gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome
      (PCOS). METHODS: We evaluated 34 GDM in women with PCOS and 70 GDM in women
      without PCOS in this prospective study. All GDM women were treated with medical
      nutrition therapy (MNT). Pre-pregnancy clinical data, fasting glucose, fasting
      insulin (FINS), blood lipid, homeostasis model assessment index of insulin
      resistance (HOMA-IR) and perinatal outcomes were investigated. RESULTS: GDM in
      women with PCOS had higher pre-pregnancy body mass index (BMI), higher incidence
      of overweight than in the non-PCOS group (each P<0.001). Incidence of history of
      infertility was also significantly higher in the PCOS group than in the non-PCOS
      group (20.6% vs. 2.9%, P<0.01). A higher incidence of early pregnancy loss (EPL)
      was found in the PCOS group than in the non-PCOS group (20.6% vs. 7.1%, P<0.05).
      Significantly higher in vitro fertilization and embryo transfer (IVF-ET) rate and
      insulin administration was also observed in the PCOS group than in the controls.
      No significant difference was found in the prevalence of preeclampsia, premature
      delivery, macrosomia, fetal death and neonatal congenital anomaly between GDM in
      women with and without PCOS (all P>0.05). [corrected] CONCLUSIONS: Compared with
      the controls, no significant increase in the incidence of adverse perinatal
      outcomes was detected in GDM in women with PCOS by appropriate management.

PMID- 20146659
TI  - Retinol-binding protein 4: a novel adipokine implicated in the genesis of LGA in
      the absence of gestational diabetes mellitus.
AB  - OBJECTIVE: Adipokines (cytokines produced by adipose tissue) play a major role in
      the control of body weight and energy distribution. Retinol-binding protein 4
      (RBP4), only recently recognized as an adipokine, has been proposed to modulate
      systemic insulin sensitivity. The goal of this study was to determine whether
      there is an association between maternal plasma RBP4 concentration and the birth
      of a large-for-gestational-age (LGA) newborn in women with and without
      gestational diabetes mellitus (GDM). STUDY DESIGN: This cross-sectional study
      included pregnant women at term in the following groups: 1) normal pregnancy with
      an appropriate-for-gestational-age (AGA) neonate (n=64); 2) normal pregnancy with
      an LGA neonate (n=44); 3) GDM with an AGA neonate (n=55); and 4) GDM with an LGA
      neonate (n=42). Maternal plasma RBP4 concentration was determined by ELISA.
      Parametric and non-parametric statistics were used for analyses. RESULTS: 1)
      Patients with GDM, either with AGA or LGA neonates, had a higher median plasma
      concentration of RBP4 than normal pregnant women who delivered an AGA neonate
      (P=0.01 and P=0.008, respectively); 2) mothers without GDM but with LGA neonates
      had a higher median plasma concentration of RBP4 than those with normal pregnancy
      and AGA newborns (P=0.001); 3) these findings remained significant after
      adjusting for maternal age, body mass index and gestational age at blood
      sampling. CONCLUSION: GDM is characterized by alterations in maternal circulating
      RBP4 concentrations akin to those of Type 2 diabetes mellitus. RBP4
      concentrations in maternal plasma may play a role in accelerated fetal growth in
      the absence of overt carbohydrate intolerance.

PMID- 20146660
TI  - The frequency and clinical significance of intra-amniotic infection and/or
      inflammation in women with placenta previa and vaginal bleeding: an unexpected
      observation.
AB  - OBJECTIVE: Idiopathic vaginal bleeding, a common complication of pregnancy,
      increases the risk of small-for-gestational age (SGA) neonate, preeclampsia and
      preterm delivery and can be the only clinical manifestation of intra-amniotic
      infection and/or inflammation (IAI). Placenta previa is thought to be protective
      against ascending intrauterine infection, yet an excess of histologic
      chorioamnionitis has been reported in this condition. The aim of this study was
      to determine the frequency and clinical significance of IAI in women with
      placenta previa and vaginal bleeding in the absence of preterm labor. STUDY
      DESIGN: A retrospective cohort study including 35 women with placenta previa and
      vaginal bleeding <37 weeks of gestation who underwent amniocentesis was
      undertaken. Patients with multiple gestations were excluded. Intra-amniotic
      infection was defined as a positive culture for microorganisms, and intra
      amniotic inflammation as an elevated amniotic fluid interleukin (IL)-6
      concentration. IL-6 concentrations were determined by ELISA in 28 amniotic fluid
      samples available. Non-parametric statistics were used for analysis. RESULTS: 1)
      The prevalence of intra-amniotic infection was 5.7% (2/35), and that of IAI was
      17.9% (5/28); 2) the gestational age at delivery was lower in patients with IAI
      than in those without IAI [29.4 weeks, interquartile range (IQR): 23.1-34.7 vs.
      35.4 weeks, IQR: 33.9-36.9; P=0.028]; and 3) patients with placenta previa and
      IAI had a higher rate of delivery within 48 h (80% (4/5) vs. 19% (4/21); P=0.008)
      than those without IAI. CONCLUSIONS: Patients with placenta previa presenting
      with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and IAI
      in 17.9%. IAI in patients with placenta previa and vaginal bleeding is a risk
      factor for preterm delivery within 48 h.

PMID- 20146662
TI  - Towards high resolution optical imaging of beta cells in vivo.
AB  - Endocrine beta cells produce and release insulin in order to tightly regulate
      glucose homeostasis and prevent metabolic pathologies such as Diabetes Mellitus.
      Optical imaging has contributed greatly to our current understanding of beta cell
      structure and function. In vitro microscopy of beta cell lines has revealed the
      localization of molecular components in the cell and more recently their dynamic
      behavior. In cultured islets, interactions of beta cells with other islet cells
      and the matrix as well as paracrine and autocrine signaling or reaction to
      nutrients have been studied. Lastly, microscopy has been performed on tissue
      sections, visualizing the islets in an environment closer to their natural
      surroundings. In most efforts to date, the samples have been isolated for
      investigation and hence have by definition been divorced from their natural
      environments and deprived of vascularization and innervations. In such a setting
      the beta cells lack the metabolic information that is primordial to their basic
      function of maintaining glucose homeostasis. We review optical microscopy; its
      general principles, its impact in decoding beta cell function and its recent
      developments towards the more physiologically relevant assessment of beta cell
      function within the environment of the whole organism. This requires both large
      imaging depth and fast acquisition times. Only few methods can achieve an
      adequate compromise. We present extended focus Optical Coherence Microscopy
      (xfOCM) as a valuable alternative to both confocal microscopy and two photon
      microscopy (2PM), and discuss its potential in interpreting the mechanisms
      underlying glucose homeostasis and monitoring impaired islet function.

PMID- 20146663
TI  - MR imaging of pancreatic islets: tracking isolation, transplantation and
      function.
AB  - The increasing global incidence of diabetes and advancements in clinical
      pancreatic islet transplantation for the treatment of Type I diabetes have
      renewed the interest in understanding the variations of beta cell mass and
      function relative not only to transplant outcome but also to the onset and
      progression of diabetes. A deeper comprehension of the molecular and cellular
      processes involved in pancreatic islet inflammation and cytotoxicity is necessary
      to further improve efficacy of islet transplantation and to develop new therapies
      aimed at preserving beta cell function in pathological conditions. Available
      diagnostic methods based on metabolic response are unsuitable as they lack
      correlation to islet mass, viability and function. Great emphasis has been placed
      on developing noninvasive imaging technologies which enable the tracking of both
      endogenous and transplanted islet mass and potentially function overtime, the
      characterization of changes in islet vasculature and the degree of T-cell
      infiltration during insulitis. Among the more relevant modalities are magnetic
      resonance, positron emitted tomography, single photon emission computed
      tomography, bioluminescence and fluorescence optical imaging. This review focuses
      on the most recent advancements in magnetic resonance imaging (MRI) of pancreatic
      islets. In-vitro approaches aimed at characterizing the potency of isolated
      islets as well as in-vivo advancements in the assessment of transplanted beta
      cell mass are presented together with the significant progress made in the in
      vivo imaging of the endocrine pancreas and islet vasculature and inflammation.
      Different experimental approaches are compared via their advantages and
      limitations with respect to their clinical implementation.

PMID- 20146664
TI  - What are the potential benefits of clinical beta-cell imaging in diabetes
      mellitus?
AB  - Previously, studies of the endocrine pancreatic beta-cell were mainly performed
      ex vivo by morphological means. This data supported the analysis of
      pathophysiological changes in the pancreatic islet during insults such as
      diabetes mellitus. Metabolic testing of the pancreatic islet by assaying hormone
      parameters such als plasma insulin or C-peptide combined with more or less
      sophisticated calculations allowed conclusions about states of insulin resistance
      or secretory failure. It also allowed certain correlations of endocrine function
      with beta-cell mass. Today, with firmer pathophysiological concepts about beta
      cell failure, modern protocols of islet transplantation, and drugs on the market
      coming with promises of preservation or even expansion of beta-cell mass in
      diabetes mellitus it has become very attractive to search for tools measuring
      beta-cell mass, if possible even repeatingly in the same organism in vivo. From a
      clinical point of view, the potential of pancreatic beta-cell mass imaging
      technologies is looked upon with high expectations. Methodologically, the
      decisive question is whether it is likely that future beta-cell imaging will
      provide significant advantages over the metabolic methods already in hand. With
      new in vivo tools, studies of beta-cell mass and function may offer even new
      approaches stratifying patients to anti-diabetic therapies.

PMID- 20146661
TI  - Evidence for differential regulation of the adipokine visfatin in the maternal
      and fetal compartments in normal spontaneous labor at term.
AB  - OBJECTIVE: Visfatin, a novel adipokine with metabolic and immunoregulatory
      properties, has been implicated in the regulation of fetal growth, as well as in
      preterm labor. A gap in knowledge is whether spontaneous labor at term is
      associated with changes in the maternal and fetal concentrations of visfatin. The
      aim of this study was to determine if the presence of labor at term is associated
      with alterations in maternal and neonatal plasma visfatin concentrations. STUDY
      DESIGN: This cross-sectional study included 50 normal pregnant women at term and
      their appropriate-for-gestational age (AGA) neonates in the following groups: 1)
      25 mother-neonate pairs delivered by elective cesarean section without
      spontaneous labor, and 2) 25 mother-neonate pairs who delivered vaginally
      following spontaneous labor. Maternal plasma and cord blood visfatin
      concentrations were determined by ELISA. Non-parametric statistics were used for
      analyses. RESULTS: 1) The median visfatin concentration was higher in umbilical
      cord plasma of neonates born following a spontaneous labor at term than that of
      those who were born by an elective cesarean section (P=0.02); 2) in contrast, the
      median maternal plasma visfatin concentration did not differ significantly
      between patients with and without labor (P=0.44); and 3) there was a significant
      correlation between umbilical cord plasma concentration of visfatin and both
      maternal visfatin concentration (r=0.54, P=0.005) and gestational age (GA) at
      delivery (r=0.58; P=0.002) only in the absence of labor. CONCLUSION: Term labor
      is associated with increased fetal, but not maternal, circulating visfatin
      concentrations. Previous reports indicate that preterm labor leading to preterm
      delivery is characterized by an increase in maternal plasma concentrations of
      visfatin. The observations reported herein support the view that there are
      fundamental differences in the endocrine and metabolic adaptations in normal
      labor at term and preterm labor.

PMID- 20146665
TI  - Identification of new pancreatic beta cell targets for in vivo imaging by a
      systems biology approach.
AB  - Systems biology is an emergent field that aims to understand biological systems
      at system-level. The increasing power of genome sequencing techniques and ranges
      of other molecular biology techniques is enabling the accumulation of in-depth
      knowledge of biological systems. This growing information, properly quantified,
      analysed and presented, will eventually allow the establishment of a system-based
      cartography of different cellular populations within the organism, and of their
      interactions at the tissue and organ levels. It will also allow the
      identification of specific markers of individual cell types. Systems biology
      approaches to discover diagnostic markers may have an important role in diabetes.
      There are presently no reliable ways to quantify beta cell mass (BCM) in vivo,
      which hampers the understanding of the pathogenesis and natural history of
      diabetes, and the development of novel therapies to preserve BCM. To solve this
      problem, novel and specific beta cell biomarkers must be identified to enable
      adequate in vivo imaging by methods such as Positron Emission Tomography (PET).
      The ideal biomarker should allow measurements by a minimally invasive technology
      enabling repeated examinations over time, should identify the early stages of
      decreased BCM, and should provide information on progression of beta cell loss
      and eventual responses to agents aiming to arrest or revert beta cell loss in
      diabetes. The present review briefly describes the "state-of-the-art" in the
      field, and then proposes a step-by-step systems biology approach for the
      identification and initial testing of novel candidates for beta cell imaging.

PMID- 20146667
TI  - Development of radiotracers for the determination of the beta-cell mass in vivo.
AB  - The changes in beta-cell mass (BCM) during the course of diabetes are not yet
      well characterized. A non-invasive method to measure the BCM in vivo would allow
      us to study the BCM during the onset and progression of the diseases caused by
      beta-cell dysfunction. PET and SPECT imaging are attractive approaches to
      determine the BCM because of their high sensitivity and the possibility to
      quantitatively analyze the images. Several targets and their corresponding
      radiotracers have been examined for their ability to determine the BCM including
      radiolabeled antibodies, antibody fragments, peptides and small molecules.
      Although some of these tracers show promising results, there is still no reliable
      method to determine the beta-cell mass in vivo. In this review, the targets and
      the corresponding radiotracers evaluated so far for the determination of the BCM
      in vivo in humans will be discussed.

PMID- 20146668
TI  - A novel EP-involved pathway for iron release from soya bean seed ferritin.
AB  - Iron in phytoferritin from legume seeds is required for seedling germination and
      early growth. However, the mechanism by which phytoferritin regulates its iron
      complement to these physiological processes remains unknown. In the present
      study, protein degradation is found to occur in purified SSF (soya bean seed
      ferritin) (consisting of H-1 and H-2 subunits) during storage, consistent with
      previous results that such degradation also occurs during seedling germination.
      In contrast, no degradation is observed with animal ferritin under identical
      conditions, suggesting that SSF autodegradation might be due to the EP (extension
      peptide) on the exterior surface of the protein, a specific domain found only in
      phytoferritin. Indeed, EP-deleted SSF becomes stable, confirming the above
      hypothesis. Further support comes from a protease activity assay showing that EP
      1 (corresponding to the EP of the H-1 subunit) exhibits significant serine
      protease-like activity, whereas the activity of EP-2 (corresponding to the EP of
      the H-2 subunit) is much weaker. Consistent with the observation above, rH-1
      (recombinant H-1 ferritin) is prone to degradation, whereas its analogue, rH-2,
      becomes very stable under identical conditions. This demonstrates that SSF
      degradation mainly originates from the serine protease-like activity of EP-1.
      Associated with EP degradation is a considerable increase in the rate of iron
      release from SSF induced by ascorbate in the amyloplast (pH range, 5.8-6.1). Thus
      phytoferritin may have facilitated the evolution of the specific domain to
      control its iron complement in response to cell iron need in the seedling stage.

PMID- 20146669
TI  - Getting a camel through the eye of a needle: the import of folded proteins by
      peroxisomes.
AB  - Peroxisomes are a family of organelles which have many unusual features. They can
      arise de novo from the endoplasmic reticulum by a still poorly characterized
      process, yet possess a unique machinery for the import of their matrix proteins.
      As peroxisomes lack DNA, their function, which is highly variable and dependent
      on developmental and/or environmental conditions, is determined by the post
      translational import of specific metabolic enzymes in folded or oligomeric
      states. The two classes of matrix targeting signals for peroxisomal proteins
      [PTS1 (peroxisomal targeting signal 1) and PTS2] are recognized by cytosolic
      receptors [PEX5 (peroxin 5) and PEX7 respectively] which escort their cargo
      proteins to, or possibly across, the peroxisome membrane. Although the membrane
      translocation mechanism remains unclear, it appears to be driven by
      thermodynamically favourable binding interactions. Recycling of the receptors
      from the peroxisome membrane requires ATP hydrolysis for two linked processes:
      ubiquitination of PEX5 (and the PEX7 co-receptors in yeast) and the function of
      two peroxisome-associated AAA (ATPase associated with various cellular
      activities) ATPases, which play a role in recycling or turnover of the
      ubiquitinated receptors. This review summarizes and integrates recent findings on
      peroxisome matrix protein import from yeast, plant and mammalian model systems,
      and discusses some of the gaps in our understanding of this remarkable protein
      transport system.

PMID- 20146666
TI  - In vivo beta-cell imaging with VMAT 2 ligands--current state-of-the-art and
      future perspective.
AB  - In diabetic disease, blood glucose, HbA1c and insulin levels qualify as
      biomarkers reflecting endocrine pancreas function, but their shortfall in being
      truly useful predictors or surrogate endpoints of "abnormal processes or disease"
      lies in that alteration in their levels are dependent on a variety comorbidities
      and occur too late in the disease process to be useful sentinels. Non invasive
      imaging of molecular targets within the beta cell carry the promise of revealing
      quantitative information about beta-cell mass that can, at least theoretically,
      be used to monitor, in real-time, the natural history of T1DM progression, assess
      novel therapies designed to drive the proliferation and differentiation of
      endogenous beta cell progenitors, appraise methods of preserving mature beta cell
      mass as well as to track the function and viability of transplanted cells and
      tissues. In this article, we review and deconstruct available information
      regarding the methodology of making non invasive measurements of VMAT2 in the
      pancreas and the validity of these measurements to estimate beta cell mass in
      vivo.

PMID- 20146670
TI  - Adhesamine, a new synthetic molecule, accelerates differentiation and prolongs
      survival of primary cultured mouse hippocampal neurons.
AB  - Attachment to the substrate is essential for both survival and differentiation of
      various kinds of cells, such as neurons and epithelial cells. We recently found a
      small synthetic molecule, adhesamine, which boosts adhesion and growth of
      mammalian cells. In the present study, we applied adhesamine to primary cultured
      hippocampal neuronal cells and compared its effects with those of PLL (poly-L
      lysine), which is widely used as a substrate for cell cultures. Neurons grown on
      adhesamine-coated coverslips survived for up to 1 month without a feeder layer of
      glial cells, and had greater viability than cells grown on PLL-coated coverslips.
      Morphological analysis revealed that neurons cultured with adhesamine exhibited
      earlier differentiation, i.e. earlier axonal outgrowth and dendritic maturation
      with enhanced neurite branching, than neurons cultured with PLL. Synaptic
      formation and postsynaptic responses were evident as early as 4 days in cells
      cultured with adhesamine. Acceleration of differentiation is mediated by earlier
      activation of the signalling pathways from heparan sulfate in the extracellular
      matrix to both FAK (focal adhesion kinase) and MAPK (mitogen-activated protein
      kinase). Improved survival rates and accelerated maturation of neurons exposed to
      adhesamine suggest that this completely synthetic molecule may be a useful
      reagent for culturing neuronal cells.

PMID- 20146671
TI  - [Spousal concordance for factors related to metabolic syndrome in families of
      patients with premature coronary heart disease].
AB  - PURPOSE: To elucidate risk factors concordance between spouses in families of
      patients with "premature" coronary heart disease (CHD). METHODS: We examined 174
      spouse pairs. There were 174 probands with "premature" (onset before 55 years)
      CHD aged 32-63 years and 174 their spouses aged 28-63 years. Among probands 18.4%
      had angina pectoris only and 81.6% had history of myocardial infarction. There
      were 10 patients with CHD among spouses (5.75%). Characteristics studied included
      alcohol consumption, tobacco smoking, education, body mass index (BMI), waist
      circumference (WC), heart rate, systolic and diastolic blood pressure (DBP),
      total, low and high density lipoprotein cholesterol, triglycerides (TG),
      apoproteins -I and B, lipoprotein (a), blood glucose and insulin, homeostasis
      model assessment-insulin resistance (HOMA IR), fibrinogen, activity of
      plasminogen activator inhibitor type 1. Concordance of variables of continuous
      and ordinal type was estimated by Spearmanis rank correlation coefficients
      adjusted for sex and age. Pairs were divided according to proband age (32-47 and
      35-63 years) and spousal concordance for characteristics studied was evaluated
      separately in 2 groups distinguished by age of proband (probands 32-47, spouses
      28-53 years, and probands 48-63, spouses 35-63 years) with presumably different
      duration of marriage/cohabitation. RESULTS: Registered characteristics of spouses
      except apo -I correlated positively. Correlations between 9 characteristics were
      significant: education, insulin, HOMA IR, WC (R=0.608, 0.424, 0.421, 0.294; all
      p=0.0001), glucose (R=0.261; p=0.0007), TG and fibrinogen (both R=0.222; p=0.0036
      and 0.0063, respectively), BMI and DBP (R=0.195 and 0.185, respectively; both
      p<0.016). All correlations were similar in groups of "younger" and "older" pairs
      with exception of PAI 1 activity (R = -0.035 and 0.320, respectively; p=0.042).
      CONCLUSION: In families of patients with premature CHD we found various degree of
      spousal concordance for risk factors mostly those considered to be related to
      metabolic syndrome. Correlations between risk factors levels in groups with
      presumably different duration of marriage were similar suggesting that
      concordance was due to assortative mating.

PMID- 20146673
TI  - [Peculiarities of dynamics and prognostic value of NT-proBNP level in different
      variants of treatment of patients with acute coronary syndrome].
AB  - Aim of the study was to assess dynamics of NT proBNP in ACS as well as to analyze
      effect of different methods of treatment on the level of the parameter and its
      prognostic value. MATERIAL AND METHODS: Patients aged 30-70 years were included
      into the study: 52 patients with ST segment elevation ACS (STEACS), 61 patients
      with non ST-segment elevation ACS (NSTEACS). Control group comprised 20 people of
      the same age without ischemic heart disease. In all patients serum was taken for
      subsequent measurement of NT proBNP at admission, on day 3 of hospitalization,
      and before discharge (days 7-10). RESULTS: In ACS baseline NT proBNP
      concentration was significantly higher than in stable angina and in control
      group. During period of hospitalization NT proBNP level rose in the group of
      patients with STEACS and fell in the group of patients with NSTEACS. After early
      restoration of coronary blood flow (less than 4 hours after onset on the pain
      syndrome) in patients with STEACS dysfunction of the left ventricular myocardium
      was less pronounced (NT proBNP level was lower). High level of NT proBNP was an
      unfavorable prognostic factor in ACS irrespective of the selected tactics of
      treatment.

PMID- 20146672
TI  - [Analysis of polymorphism of three positions of promoter region of TNF- gene in
      patients with ischemic heart disease, unstable angina and myocardial infarction].
AB  - We studied polymorphism of three positions of promoter region of TNF alpha gene
      in patients with ischemic heart disease (IHD), development of unstable angina
      (UA) and acute myocardial infarction (MI). Analysis of frequencies of genotypes
      in position A308 showed that heterozygotness in patients with cardiovascular
      diseases significantly decreased. Lowering of risk of development of MI in
      carriers of heterozygous variant of the gene in position A308 was shown. In the
      group of patients with Q wave MI frequency of A308 AA genotype rose.

PMID- 20146674
TI  - [Non-ST-elevation acute coronary syndrome. Comparison of effects of atorvastatin
      and rosuvastatin on blood levels of lipids and markers of inflammation].
AB  - Data on rapid effects of statins in patients (pts) with acute coronary syndrome
      (ACS) are mostly from trials of atorvastatin (ATO). We hypothesized that due to
      high potency 10 mg of rosuvastatin (ROS) would produce same changes of lipids and
      inflammation markers as 40 mg ATO. METHODS: We openly randomized 53 pts (69.7+/
      10.1 years, 58.5% - man) within 36 h of non ST elevation (NSTE) ACS (56.6% NSTE
      myocardial infarction) to ROS 10 (n=19), ATO 40 (n=19) mg/day or no statin
      (n=15). Pts with low density lipoprotein cholesterol (LDL-C) >6, triglycerides
      (TG) >4.5 mmol/l, C-reactive protein (CRP) >10 mg/l (non-fasting sample) were not
      included. LDL-C, high density lipoprotein (HDL)-C, TG, apolipoproteins A-1
      (apoA), and B (apoB), high sensitivity CRP, tumor necrosis factor-alpha
      (TNFalpha), interleukin-6 (IL-6) were measured in fasting blood sampled at
      randomization and 2 weeks later. RESULTS: Both statins caused similar decreases
      of LDL-C (-44.0% ROS, -50% ATO; both p<0.00001 vs control [-4%]). TG
      significantly rose in ROS (p=0.042) and control (p=0.008) groups but not in ATO
      group (p=0.615). HDL-C decreased similarly in 3 groups. ApoA-1 did not differ
      between 3 groups at all time points. ApoB decreased more in ATO (-32.6%), than in
      ROS (-24%) group (p=0.049). CRP and IL-6 changes from baseline were
      insignificant. In ROS group CRP had tendency to decrease but same tendency took
      place in control. TNFalpha significantly increased in all groups. There were no
      significant differences between 3 groups in inflammation markers. CONCLUSION: In
      pts with NSTEACS effect on lipids of ROS 10 mg was somewhat inferior to ATO 40
      mg/day. Unexpectedly ATO and ROS during first 14 days of NSTEACS produced no
      significant effect on inflammation markers possibly because of insufficient dose
      of both.

PMID- 20146675
TI  - [Prognostic value of cardiovascular autonomic neuropathy in patients with
      combination type 2 diabetes mellitus and chronic heart failure].
AB  - Type 2 diabetes mellitus (DM) is often combined with chronic heart failure (CHF).
      Cardiovascular autonomic neuropathy (CAN) is widely spread complication of DM. In
      this work we studied effect of CAN on the course of CHF in patients with type 2
      DM. We have shown unfavorable effect of CAN on the rate of development of
      myocardial infarction and course of CHF in patients with type 2 DM. We have
      demonstrated participation of CAN in pathogenesis of CHF and necessity of
      diagnostics of CAN in patients with combination of type 2 DM and CHF.

PMID- 20146676
TI  - [Application of methods of renal replacement therapy for abolishment of
      hyperhydration in patients with decompensated chronic heart failure].
AB  - Slow continuous ultrafiltration (SCUF), continuous veno venous haemofiltration
      (CVVHF) are alternative to diuretics methods of treatment of patients with
      chronic heart failure (CHF), edematous syndrome. METHODS: Patients of both sexes
      aged 30-82 years with functional class II-IV CHF were included because of
      decompensation of CHF. Randomization: experiment - 19 patients, 3-4 component
      therapy plus SCUF or CVVHF; control - 3-4 component therapy plus intravenous
      furosemide. EXAMINATION: I n at baseline, II n after compensation of CHF.
      RESULTS: Delta weight (kg) - experiment -10.1+/-1.08, control -1.92+/-0.83,
      p=0.00001; Delta left ventricular ejection fraction - experiment +10.09+/-2.26,
      control +0.52+/-1.14, p=0.0007; pulmonary artery systolic pressure (mm Hg) -
      experiment -12.32+/-3,43, control -4.05 +/-2.07, p=0.029; Delta 6 min walk test:
      experiment +304.22+/-39.4, control +91.91+/-23.4, p=0.00003; Delta glomerular
      filtration rate - experiment -1.16+/-3.23, control +4.44+/-3.68, p=0.85; duration
      of hospitalization (days) - experiment 17.26+/-1.43, control 17.52+/-1.02,
      p=0.59. We did not observe complications related to renal replacement therapy.
      CONCLUSION: SCUF and CVVHF are safe for patients. In decompensated CHF SCUF and
      CVVHF provide greater weight reduction and fluid removal than intravenous
      diuretics, abolish hypervolemia what cause improvement of myocardial
      contractility.

PMID- 20146677
TI  - [Characteristics of central pulse wave in young men with various phenotypes of
      arterial pressure].
AB  - In this work we compared parameters of central arterial pressure (AP) on the
      basis of analysis of pulse wave in young men in dependence of AP phenotype
      determined by repetitive clinical measurements and 24 hour AP monitoring
      (24HAPM). Comparison of characteristics of central pulse wave was carried out in
      12 men with normal AP, 36 men with arterial hypertension (AH) according to
      clinical measurements and 24HAPM, and 17 men with white coat hypertension (WCH).
      Mean age was 21.0+/-2.1 years. Differences in levels of pulse pressure (PP)
      between groups with AH were revealed only at the level of the aorta. Studied
      patients with normal AP and 24HAPM did not differ by such characteristics as
      index of increment and reflected wave appearance time. Studied patients with AH
      confirmed by 24HAPM were characterized by significantly greater augmentation of
      central PP (100.0+/-12.6% vs 96.6+/-11.8% in persons with normal AP and 95.6+/
      15.0% with WCH, p<0.05), earlier appearance of reflected wave (149.2+/-18.9 ms vs
      160.6+/-16.2 and 160.3+/-28.6 ms, respectively, p<0.05), high rate of pulse wave
      propagation (8.6+/-1.2 m/s vs 7.2+/-1.2 and 7.0+/-1.7 m/s). Amplification was
      similar in three groups. The data obtained has shown that in men aged 18-25 years
      presence of AH, confirmed by 24HAPM) is associated with elevation of central
      systolic AP and PP and higher values of markers of both rigidity of the aorta and
      remodeling of peripheral vascular bed.

PMID- 20146678
TI  - [ATR1 gene polymorphism in patients with hypertrophic cardiomyopathy and
      hypertensive heart].
AB  - Aim of the study was analysis of dependence of clinical picture and degree of
      severity of left ventricular hypertrophy (LVH) on polymorphism A/C of ATR1 gene
      in patients with hypertrophic cardiomyopathy (HCMP) and hypertensive disease
      (HD). With the method of polymerase chain reaction genotyping for polymorphic
      markers of A/C of ATR1 gene was carried out in 35 patients with HCMP and 33
      patients with LVH developed at the background of long lasting HB. In the work we
      used clinico-instrumental methods of investigation (electrocardiography - ECG,
      echocardiography). It was revealed as result of the study that in HCMP type AA in
      comparison with type AC of ATR1 gene was associated with addition of arterial
      hypertension, presence of left ventricular outflow tract obstruction, greater
      severity of heart failure. In case of combination of HD with LVH type AA in
      comparison with types AC and CC of ATR1 gene is associated with more pronounced
      LVH.

PMID- 20146679
TI  - [Relationship between activity of fibrinolysis, parameters of lipid spectrum and
      carbohydrate metabolism].
AB  - In this work analysis of results of a prospective populational cohort study
      "Stress and health in Russia" is presented. We included in the study inhabitants
      of Moscow randomly sampled from the population of men and women aged > or =55
      years. Aim of the present work consisted in the study of relationship of activity
      of fibrinolysis and main parameters of the system of lipoproteines providing
      transport of lipids in blood serum and system controlling utilization of glucose
      by tissues. In dependence on fibrinolytic activity all examined persons were
      divided into 3 groups: with hypofibrinolysis (group 1, n=41.5%), with
      normofybrinolysis (group 2, n=41.9%), and hyperfibrinolysis (group 3, n=16.6%).
      In persons of group 1 low fibrinolytic activity and high level of fibrinogen were
      combined with atherogenic spectrum of blood serum lipids and elevated level of
      insulin at normal level of glucose. In patients of group 3 elevated fibrinolytic
      activity was combined with more favorable composition of blood lipids, lower
      levels of insulin and glucose and absence of obesity. At study of relation
      between fibrinoltic activity and a row of clinical states by the method of
      logistic regression a tendency to elevation of prevalence of myocardial
      infarction in persons with hypofibrinolysis was found while in persons with
      hyperfibrinolysis a significant lowering of prevalence of arterial hypertension,
      ischemic heart disease, and angina pectoris was observed.

PMID- 20146680
TI  - [Mechanism of stimulation of angiogenesis in ischemic myocardium with the help of
      adipose tissue stromal cells].
AB  - Stromal cells from subcutaneous adipose tissue (adipose derived stromal cells -
      ASCs) are perspective for cell therapy of ischemic states because of ability to
      stimulate growth of vessels. For the elucidation of mechanisms of angiogenic
      action of ASCs we used the model of co-cultivation of ASCs with cells isolated
      from postnatal hearts (fraction of cardiomyocutes - CMC). CMC fraction contained
      mature cardiomyocytes, endothelial and progenitor cells. On the 2-nd day
      spontaneously beating colonies of CMC with growing from them CD31-positive
      capillary-like structures were formed in CMC culture. Observed structures were
      unstable and came apart after 5 days of cultivation. At co-cultivation of CMC
      with ASCs formation of stable ramified CD31-positive structures was observed.
      Using the method of co-cultivation of CMC with mitomycin C treated ASCs and the
      method of immune magnetic depletion for removal of epithelial cells from the CMC
      fraction we found that ASCs stimulates formation of capillary like structure at
      the account of secretion of angiogenic factors, stabilization of forming CD31
      positive structures at the account of intercellular contacts and stimulation of
      endothelial differentiation of progenitor cells present in CMC fraction.

PMID- 20146681
TI  - [Atrial myocardial deformation in healthy individuals of two-dimensional strain].
AB  - The biggest problem in the evaluation of the function of atria is a lack of
      knowledge about normal values. There are no data on the use of two-dimensional
      strain (2-DS) for the assessment of atrial myocardial deformation. The aim of
      this study was to find out the feasibility of 2-DS in the evaluation of the
      function of atrial myocardium in healthy individuals. We have evaluated 30
      healthy persons with normal values of standard echocardiography. 2-DS data were
      recorded in each patient for the lateral, septal, posterior, inferior and
      anterior walls of the left atrium and also of the lateral wall of the right
      atrium. We have measured peak strain (epsilon), peak strain rate (SR), peak
      displacement of each segment during the contractile, reservoir and conduit atrial
      phases. The timing of mechanical events also were assessed at the left atrium and
      right atrium walls and interatrial septum. Our study has demonstrated the ability
      to use 2-DS Echo in evaluation of epsilon/SR of atrial myocardium in different
      parts of atria in healthy patients. This method is easy to use and it is useful
      in assessment of mechanical function of atria.

PMID- 20146682
TI  - [Changes of interleukin-6 in various forms of ischemic heart disease].

PMID- 20146683
TI  - [European congress of cardiologists 2009. Results of large clinical studies].

PMID- 20146684
TI  - [Sudden death in young athletes].

PMID- 20146685
TI  - [Optimal method of revascularization in patients with multivessel coronary artery
      involvement for application of drug eluting stents: percutaneous coronary
      interventions in comparison with coronary bypassing].
AB  - Drug eluting stents (DES) which appeared in the beginning of 21-st century
      allowed to elevated percutaneous coronary interventions (PCI) to a novel level.
      High efficacy of DES has been proven in a row of conducted clinical studies:
      after their implantation low percentage of in stent restenosis and low rate of
      repetitive target vessel revascularizations have been obtained. At the same time
      there occurred definite improvements in the technique of coronary bypass surgery.
      Therefore a question of choice of optimal method of revascularization in patients
      with multivessel lesions remains open. In this review we present results of a row
      of large studies in which coronary bypassing and PCI with implantation of DES has
      been compared in patients with multivessel lesions.

PMID- 20146686
TI  - [An experience with the use of direct renin inhibitor aliskiren in a patient with
      obesity and arterial hypertension].

PMID- 20146688
TI  - Sleep disorders in children.
AB  - Although sleep disorders such as insomnia and obstructive sleep apnea are common
      in both children and adults, the clinical features and treatments for these
      conditions differ considerably between these two populations. Whereas an adult
      with obstructive sleep apnea typically presents with a history of obesity,
      snoring, and prominent daytime somnolence, a child with the condition is more
      likely to present with normal body weight, tonsillar hypertrophy, and
      inattentiveness during school classes. The adult with suspected sleep apnea
      almost always undergoes a baseline polysomnogram and proceeds to treatment only
      if this test confirms the diagnosis, while many children with suspected sleep
      apnea are treated empirically with adenotonsillectomy without ever receiving a
      sleep study to verify the diagnosis. This article reviews sleep disorders in
      children, with a particular focus on age-related changes in sleep, conditions
      that primarily affect children, and disorders for which clinical manifestations
      and treatment differ substantially from the adult population.

PMID- 20146690
TI  - Lewy body pathology in fetal grafts.
AB  - Although fetal nigral transplants have been shown to survive grafting into the
      striatum, increased [(18)F]6-fluroro-L-3,4-dihydroxyphenylalanine ((18)F-DOPA)
      uptake and improved motor function in open-label assessments have failed to
      establish any clinical benefits in double-blind, sham-controlled studies. To
      understand morphological and neurochemical alterations of grafted neurons, we
      performed postmortem analyses on six Parkinson's disease (PD) patients who had
      received fetal tissue transplantation 18-19 months, 4 years, and 14 years
      previously. These studies revealed robust neuronal survival with normal
      dopaminergic phenotypes in 18-month-old grafts and decreased dopamine transporter
      and increased cytoplasmic alpha-synuclein in 4-year-old grafts. We also found a
      decline of both dopamine transporter and tyrosine hydroxylase and the formation
      of Lewy body-like inclusions in 14-year-old grafts, which stained positive for
      alpha-synuclein and ubiquitin proteins. These pathological changes suggest that
      PD is an ongoing process that affects grafted cells in the striatum in a manner
      similar to how resident dopamine neurons are affected in the substantia nigra.

PMID- 20146689
TI  - REM sleep behavior disorder: Updated review of the core features, the REM sleep
      behavior disorder-neurodegenerative disease association, evolving concepts,
      controversies, and future directions.
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested
      by vivid, often frightening dreams associated with simple or complex motor
      behavior during REM sleep. The polysomnographic features of RBD include increased
      electromyographic tone +/- dream enactment behavior during REM sleep. Management
      with counseling and pharmacologic measures is usually straightforward and
      effective. In this review, the terminology, clinical and polysomnographic
      features, demographic and epidemiologic features, diagnostic criteria,
      differential diagnosis, and management strategies are discussed. Recent data on
      the suspected pathophysiologic mechanisms of RBD are also reviewed. The
      literature and our institutional experience on RBD are next discussed, with an
      emphasis on the RBD-neurodegenerative disease association and particularly the
      RBD-synucleinopathy association. Several issues relating to evolving concepts,
      controversies, and future directions are then reviewed, with an emphasis on
      idiopathic RBD representing an early feature of a neurodegenerative disease and
      particularly an evolving synucleinopathy. Planning for future therapies that
      impact patients with idiopathic RBD is reviewed in detail.

PMID- 20146691
TI  - Congenital heart disease and brain development.
AB  - Brain and heart development occur simultaneously in the human fetus. Given the
      depth and complexity of these shared morphogenetic programs, it is perhaps not
      surprising that disruption of organogenesis in one organ will impact the
      development of the other. Newborns with congenital heart disease show a high
      frequency of acquired focal brain injury on sensitive magnetic resonance imaging
      studies in the perioperative period. The surprisingly high incidence of white
      matter injury in these term newborns suggests a unique vulnerability and may be
      related to a delay in brain development. These abnormalities in brain development
      identified with MRI in newborns with congenital heart disease might reflect
      abnormalities in cerebral blood flow while in utero. A complete understanding of
      the mechanisms of white matter injury in the term newborn with congenital heart
      disease will require further investigation of the timing, extent, and causes of
      delayed fetal brain development in the presence of congenital heart disease.

PMID- 20146693
TI  - Neurological complications of immune reconstitution in HIV-infected populations.
AB  - The introduction of highly active antiretroviral therapy (HAART) for human
      immunodeficiency virus (HIV) infection has transformed this disease from a fatal
      infection to a chronic yet manageable condition by restoring immune function. All
      the same, this restoration of immune response in some may be associated with
      deterioration in clinical status, which has been termed immune reconstitution
      inflammatory syndrome (IRIS). This syndrome often occurs in the context of an
      underlying opportunistic infection and develops after an interval of weeks to
      months after the initiation of HAART. Occasionally, IRIS may occur in the brain
      without any opportunistic infection, which presents as a T cell-mediated
      encephalitis. This paradoxical infiltration of previously immune suppressed
      patients with T cells represents a diagnostic challenge and a treatment dilemma.
      Nonetheless, CNS-IRIS with or without an opportunistic infection can range in
      severity. Severe cases can be fatal and hence require intervention with steroid
      treatment. This review discusses the diagnosis, clinical manifestations, risk
      factors, pathophysiology, and potential treatment strategies of the various forms
      of IRIS that involve the nervous system.

PMID- 20146694
TI  - Vertebrobasilar dilatative arteriopathy (dolichoectasia).
AB  - Dolichoectasia (dilatative arteriopathy) describes marked elongation, widening,
      and tortuosity of arteries. The intracranial vertebral and basilar arteries are
      preferentially involved. Dolichoectatic arteries usually have an abnormally large
      external diameter and a thin arterial wall, with degeneration of the internal
      elastic lamina, multiple gaps in the internal elastica, thinning of the media
      secondary to reticular fiber deficiency, and smooth muscle atrophy. The most
      important clinical presentations of dilatative arteriopathy include acute brain
      ischemia; a progressive course related to compression of cranial nerves, the
      brain stem, or the third ventricle; and catastrophic outcome caused by vascular
      rupture. Flow in dilated arteries can become bidirectional, resulting in reduced
      antegrade flow and thrombus formation. Elongation and angulation of arteries can
      stretch and distort the orifices of arterial branches, leading to decreased blood
      flow, especially in penetrating branches.

PMID- 20146695
TI  - Dermatomyositis and polymyositis: Clinical presentation, autoantibodies, and
      pathogenesis.
AB  - Dermatomyositis (DM) and polymyositis (PM) are autoimmune myopathies
      characterized clinically by proximal muscle weakness, muscle inflammation,
      extramuscular manifestations, and frequently, the presence of autoantibodies.
      Although there is some overlap, DM and PM are separate diseases with different
      pathophysiological mechanisms. Furthermore, unique clinical phenotypes are
      associated with each of the myositis-specific autoantibodies (MSAs) associated
      with these disorders. This review will focus on the clinical features, pathology,
      and immunogenetics of PM and DM with an emphasis on the importance of
      autoantibodies in defining unique phenotypes and, perhaps, as clues to help
      elucidate the mechanisms of disease.

PMID- 20146692
TI  - The tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results
      from mutations in the TSC1 or TSC2 genes and is associated with hamartoma
      formation in multiple organ systems. The neurological manifestations of TSC are
      particularly challenging and include infantile spasms, intractable epilepsy,
      cognitive disabilities, and autism. Progress over the past 15 years has
      demonstrated that the TSC1 or TSC2 encoded proteins modulate cell function via
      the mTOR signaling cascade and serve as keystones in regulating cell growth and
      proliferation. The mTOR pathway provides an intersection for an intricate network
      of protein cascades that respond to cellular nutrition, energy levels, and growth
      factor stimulation. In the brain, TSC1 and TSC2 have been implicated in cell body
      size, dendritic arborization, axonal outgrowth and targeting, neuronal migration,
      cortical lamination, and spine formation. Antagonism of the mTOR pathway with
      rapamycin and related compounds may provide new therapeutic options for TSC
      patients.

PMID- 20146696
TI  - Advances in the treatment of neurodegenerative disorders employing
      nanotechnology.
AB  - Due to limitations posed by the restrictive blood-brain barrier, conventional
      drug delivery systems do not provide adequate cyto-architecture restoration and
      connection patterns that are essential for functional recovery in
      neurodegenerative disorders (NDs). Nanotechnology employs engineered materials or
      devices that interact with biological systems at a molecular level and could
      revolutionize the treatment of NDs by stimulating, responding to, and interacting
      with target sites to induce physiological responses while minimizing side
      effects. This review provides a concise discussion of the current applications of
      nano-enabled drug-delivery systems for the treatment of NDs, in particular
      Alzheimer's and Parkinson's diseases, and explores the future applications of
      nanotechnology in clinical neuroscience to develop innovative therapeutic
      modalities for the treatment of NDs.

PMID- 20146697
TI  - Neurologic Wilson's disease.
AB  - Despite a long history, Wilson's disease, an autosomal recessive disease caused
      by mutations in the ATP7B gene, remains a commonly misdiagnosed import disease.
      Mutations in ATP7B result in abnormal copper metabolism and subsequent toxic
      accumulation of copper. Clinical manifestations of neurologic Wilson's disease
      include variable combinations of dysarthria, dystonia, tremor, and
      choreoathetosis. Among neurodegenerative diseases, it is unusual in that
      misdiagnosis and delay in treatment are clinically relevant because treatments
      can prevent and cure Wilson's disease, if they are given appropriately. If left
      untreated, Wilson's disease progresses to hepatic failure or severe neurologic
      disability and death, while those adequately treated have normal life spans. This
      review focuses on the neurologic features of Wilson's disease, its diagnosis, and
      treatment options.

PMID- 20146698
TI  - The progression of pathology in Parkinson's disease.
AB  - To identify the progression of pathology over the entire course of Parkinson's
      disease, we longitudinally followed a clinical cohort to autopsy and identified
      three clinicopathological phenotypes that progress at different rates. Typical
      Parkinson's disease has an initial rapid loss of midbrain dopamine neurons with a
      slow progression of Lewy body infiltration into the brain (over decades).
      Dementia intervenes late when Lewy bodies invade the neocortex. Older onset
      patients (> 70 years old) dement earlier and have much shorter disease durations.
      Paradoxically, they have far more alpha-synuclein-containing Lewy bodies
      throughout the brain, and many also have additional age-related plaque pathology.
      In contrast, dementia with Lewy bodies has the shortest disease course, with
      substantive amounts of Lewy bodies and Alzheimer-type pathologies infiltrating
      the brain. These data suggest that two age-related factors influence pathological
      progression in Parkinson's disease--the age at symptom onset and the degree and
      type of age-related Alzheimer-type pathology.

PMID- 20146699
TI  - Familial pain syndromes from mutations of the NaV1.7 sodium channel.
AB  - The literature currently suggests that voltage-gated sodium channels play a major
      role in the pathogenesis of neuropathic pain. Alterations in the expression and
      targeting of specific sodium channels within injured dorsal root ganglia neurons
      appear to predispose the neurons to abnormal firing properties, allowing for the
      development of neuropathic pain. Mutations of one particular sodium channel
      (Na(v)1.7) have been shown to cause inherited neuropathic pain in humans,
      specifically in erythromelalgia and paroxysmal extreme pain disorder. Inherited
      erythromelalgia is the first human pain syndrome to be understood at a molecular
      level, having been linked to gain-of-function mutations of Na(v)1.7. Conversely,
      a loss-of-function of the Na(v)1.7 channel can produce channelopathy-associated
      insensitivity to pain. Therefore, the Na(v)1.7 channel may provide a unique
      target for the pharmacotherapy of pain in humans. In this review article we
      summarize current knowledge regarding several different disease manifestations
      arising from changes within the Na(v)1.7 channel.

PMID- 20146701
TI  - Endocannabinoid control of gastric sensorimotor function in man.
AB  - BACKGROUND: Little is known about the physiological role of the endocannabinoid
      system in the regulation of the motility and the sensitivity of the stomach.
      Endocannabinoid system dysfunction has been hypothesized to contribute to the
      control of food intake and the pathogenesis of functional dyspepsia. AIM: To
      study the influence of rimonabant, the endocannabinoid 1 (CB1) receptor
      antagonist, on gastric sensorimotor function in healthy controls. METHODS: After
      4 days of pre-treatment with rimonabant 20 mg/day or placebo, 12 healthy
      volunteers (mean age 34 +/- 12 years, six men) participated in a placebo
      controlled, double-blind, randomized, crossover study with a gastric barostat
      assessment of gastric sensitivity to distension, gastric compliance, gastric
      accommodation and phasic motility on day 3 and a liquid nutrient challenge test
      on day 4. RESULTS: Rimonabant did not influence gastric compliance and
      sensitivity to distension. The meal-induced gastric accommodation reflex was
      significantly inhibited by rimonabant (154.3 +/- 30.9 vs. 64.3 +/- 32.4 mL, P =
      0.02). Rimonabant did not affect maximal nutrient tolerance or meal-related
      symptoms during the satiety drinking test. CONCLUSION: Endocannabinoids acting on
      the CB1 receptor are involved in the control of gastric accommodation in man.

PMID- 20146700
TI  - Epilepsy in the elderly.
AB  - The elderly, often defined as those 65 years or older, are the most rapidly
      growing segment of the population, and onset of epilepsy is higher in this age
      group than in any other. This paper reviews recent developments, including a new
      proposed definition of epilepsy, a transgenic mouse model of Alzheimer's disease
      that exhibits complex partial seizures, evidence that the highest incidence of
      epilepsy may occur after admission to a nursing home, a challenge to the vitamin
      D hypothesis of osteoporosis associated with antiepileptic drugs (AEDs), evidence
      that the genetic complement of hepatic isoenzymes is more predictive of metabolic
      rate than age, and data showing that there is considerable variability in serum
      levels of AEDs in many nursing home residents during constant dosing conditions.

PMID- 20146702
TI  - Omeprazole-Mg 20.6 mg is superior to lansoprazole 15 mg for control of gastric
      acid: a comparison of over-the-counter doses of proton pump inhibitors.
AB  - BACKGROUND: Over-the-counter (OTC) proton pump inhibitors (PPIs) relieve
      heartburn by decreasing the production of gastric acid, but may not do so with
      equal effectiveness. It is important for healthcare professionals to compare the
      ability of OTC PPIs to control gastric acid when recommending them for patients
      with frequent heartburn. AIM: To compare the effects of omeprazole-Mg 20.6 mg and
      lansoprazole 15 mg (OTC doses in the US) on 24-h steady state gastric acid
      suppression. METHODS: This single-centre, randomized, double-blind clinical study
      compared the steady-state gastric acid control of omeprazole-Mg 20.6 mg vs.
      lansoprazole 15 mg, dosed before breakfast. Volunteers were enrolled in a 3
      period, cross-over design (ABB, BAA) with 24-h gastric pH monitoring on dosing
      day 5. The primary efficacy variable was the percentage time intragastric pH was
      >4.0 over 24 h on day 5 of dosing. RESULTS: Forty subjects were enrolled; all
      completed the study. The mean (SE) percentage time pH was >4.0 was 45.7% (3.45%)
      for omeprazole-Mg 20.6 mg and 36.8% (3.45%) for lansoprazole 15 mg, an absolute
      difference of 8.9% (P < 0.0001), and a relative difference of 24.2%. Both drugs
      were well tolerated. CONCLUSION: Omeprazole-Mg 20.6 mg provided a statistically
      significantly (P < 0.0001) greater acid control than lansoprazole 15 mg.

PMID- 20146703
TI  - The year in immunology 2. Preface.

PMID- 20146704
TI  - Development of thymically derived natural regulatory T cells.
AB  - Natural regulatory T cells (nTregs) are defined by their inherent ability to
      establish and maintain peripheral self-tolerance. In recent years, the
      development of nTregs has come under close examination with the advent of
      Forkhead Box P3 protein (FOXP3)-green fluorescent protein reporter mice that
      pinpointed the initiation of FOXP3 expression within the thymus. The mechanism
      and pathway of nTreg development has only recently been studied in detail and to
      a large degree remains unclear. In this review, we will discuss our current
      understanding of nTreg lineage choice and development from a cellular and
      intracellular standpoint.

PMID- 20146705
TI  - Thymic stromal lymphopoietin.
AB  - Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine
      expressed in skin, gut, lungs, and thymus. TSLP signals via a TSLP receptor
      (TSLPR), a heterodimer of the IL-7 receptor alpha chain and the TSLPR chain. The
      TSLPR chain is closely related to the common receptor gamma chain that is
      expressed on a wide range of cell types in the adaptive and innate immune system.
      TSLP exerts a profound influence on the polarization of dendritic cells to drive
      T helper (Th) 2 cytokine production. TSLP also directly promotes T-cell
      proliferation in response to T-cell receptor activation and Th2 cytokine
      production and supports B-cell expansion and differentiation. TSLP further
      amplifies Th2 cytokine production by mast cells and natural killer T cells. These
      properties confer on TSLP a critical role in driving Th2-mediated inflammation.
      This role is supported by the finding that TSLP expression is upregulated in
      keratinocytes of atopic dermatitis skin lesions and in bronchial epithelial cells
      in asthma.

PMID- 20146707
TI  - B10 cells and regulatory B cells balance immune responses during inflammation,
      autoimmunity, and cancer.
AB  - The ability of B cells to negatively regulate cellular immune responses and
      inflammation has only recently been described. Hallmark papers from a number of
      distinguished laboratories have identified phenotypically diverse B-cell subsets
      with regulatory functions during distinct autoimmune diseases, including IL-10
      producing B cells, CD5+ B-1a cells, CD1d+ marginal zone B cells, and transitional
      2-marginal zone precursor B cells. Most recently, a numerically rare and
      phenotypically unique CD1dhiCD5+CD19hi subset of regulatory B cells has been
      identified in the spleens of both normal and autoimmune mice. CD1dhiCD5+ B cells
      with the capacity to produce IL-10 have been named B10 cells as they produce IL
      10 exclusively and are the predominant B-cell source of IL-10. Remarkably, B10
      cells are potent negative regulators of inflammation and autoimmunity in mouse
      models of disease in vivo. Herein, our current understanding of B10-cell
      development and function is reviewed in the context of previous studies that have
      identified and characterized regulatory B cells, emerging evidence for B10-cell
      regulation of tumor immunity, and the likelihood that B10 cells exist in humans.

PMID- 20146706
TI  - Dioxin and immune regulation: emerging role of aryl hydrocarbon receptor in the
      generation of regulatory T cells.
AB  - The immune toxicity of the ubiquitous environmental contaminant 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to as dioxin, has been
      studied for over 35 years but only recently has the profound immune suppression
      induced by TCDD exposure been linked to induction of regulatory T cells (Tregs).
      The effects of TCDD are mediated through its binding to the aryl hydrocarbon
      receptor (AHR), a ligand-activated transcription factor. The subsequent AHR
      dependent effects on immune responses are determined by the cell types involved,
      their activation status, and the type of antigenic stimulus. Collectively,
      studies indicate that TCDD inhibits CD4+ T cell differentiation into T helper
      (Th)1, Th2, and Th17 effector cells, while inducing Foxp3-negative and/or
      preserving Foxp3+ Tregs. Although it is not yet clear how activation of AHR by
      TCDD induces Tregs, there is a potential therapeutic role for alternative AHR
      ligands in the treatment of immune-mediated disorders.

PMID- 20146709
TI  - FcgammaRIIB, FcgammaRIIIB, and systemic lupus erythematosus.
AB  - The autoimmune disease systemic lupus erythematosus (SLE) is characterized by the
      deposition of immune complexes in organs such as the kidney. This occurs as a
      result of multiple immunological abnormalities, including the production of high
      levels of autoantibody and dysregulated handling of immune complexes. Receptors
      for the Fc portion of IgG are critically involved in immune complex handling and
      clearance and in the regulation of B-cell activation. Polymorphisms in the low
      affinity Fcgamma receptors have been associated with susceptibility to a number
      of autoimmune diseases, including SLE. We review the role of two such receptors
      in the pathogenesis of lupus-the inhibitory receptor FcgammaRIIB and the
      glycosylphosphatidylinositol-linked activatory receptor FcgammaRIIIB. Recent work
      has enhanced our understanding of the mechanism of action of the FcgammaRIIB
      I232T polymorphism and the overall role of this receptor in SLE. The human
      neutrophil antigen-1 allotypes of FcgammaRIIIB and the role of the receptor in
      SLE are discussed with regard to the recent determination of copy number
      variation in FCGR3B and the association of low copy number with SLE.

PMID- 20146708
TI  - Innate pathways to B-cell activation and tolerance.
AB  - B cells represent an important link between the adaptive and innate immune
      systems as they express both antigen-specific B-cell receptors (BCRs) as well as
      various Toll-like receptors (TLRs). Several checkpoints in B-cell development
      ensure that self-specific cells are eliminated from the mature B-cell repertoire
      to avoid harmful autoreactive responses. These checkpoints are controlled by BCR
      mediated events but are also influenced by TLR-dependent signals from the innate
      immune system. Additionally, B-cell-intrinsic and extrinsic TLR signaling are
      critical for inflammatory events required for the clearance of microbial
      infections. Factors secreted by TLR-activated macrophages or dendritic cells
      directly influence the fate of protective and autoreactive B cells. Additionally,
      naive and memory B cells respond differentially to TLR ligands, as do different B
      cell subsets. We review here recent literature describing intrinsic and extrinsic
      effects of TLR stimulation on the fate of B cells, with particular attention to
      autoimmune diseases.

PMID- 20146710
TI  - Plasmacytoid dendritic cells: key players in the initiation and regulation of
      immune responses.
AB  - Plasmacytoid dendritic cells (pDCs) are a rare population of circulating cells
      that selectively express Toll-like receptors (TLR)7 and TLR9 and have the
      capacity to produce large amounts of type I interferons (IFNs) in response to
      viruses or host-derived nucleic acid-containing complexes. Through the production
      of type I IFNs, pDCs initiate protective immunity by activating classical DCs, T
      cells, natural killer cells, and B cells. Upon activation, pDCs also
      differentiate into mature DCs and may contribute to the contraction of T-cell
      responses. In this review, we describe how pDCs are key players in the initiation
      and regulation of immune responses and discuss their emerging role in the
      pathogenesis of human diseases.

PMID- 20146711
TI  - Signaling of c-kit in dendritic cells influences adaptive immunity.
AB  - The binding of the receptor tyrosine kinase, c-kit, to its ligand, stem cell
      factor (SCF), mediates numerous biological functions. Important roles for c-kit
      in hematopoiesis, melanogenesis, erythropoiesis, spermatogenesis, and
      carcinogenesis are well documented. Similarly, activation of granulocytes, mast
      cells, and of eosinophils in particular, by c-kit ligation has long been known to
      result in degranulation with concomitant release of pro-inflammatory mediators,
      including cytokines. However, recent work from a number of laboratories,
      including our own, highlights previously unappreciated functions for c-kit in
      immunologic processes. These novel findings strongly suggest that signaling
      through the c-kit-SCF axis could have a significant impact on the pathogenesis of
      diseases associated with an immunologic component. In our own studies, c-kit
      upregulation on dendritic cells via T helper (Th)2- and Th17-inducing stimuli led
      to c-kit activation and immune skewing toward these T helper subsets and away
      from Th1 responses. Others have shown that dendritic cell treatment with
      inhibitors of c-kit activation, such as imatinib mesylate (Gleevec), favored
      breaking of T-cell tolerance, skewing of responses toward production of Th1
      cytokines, and activation of natural killer cells. These data all indicate that
      deeper understanding of, and ability to control, the c-kit-SCF axis could lead to
      improved treatment modalities aimed at redirecting unwanted and/or deleterious
      immune responses in a wide variety of conditions.

PMID- 20146714
TI  - Galectins: regulators of acute and chronic inflammation.
AB  - Galectins, beta-galactoside-binding animal lectins, are differentially expressed
      by various immune cells as well as a wide range of other cell types.
      Extracellularly, galectins are able to exhibit bivalent or multivalent
      interactions with cell-surface glycans on various immune cells and exert various
      effects. These include cytokine and mediator production, cell adhesion,
      apoptosis, and chemoattraction. In addition, they can form lattices with cell
      surface glycoprotein receptors, resulting in modulation of receptor functions,
      including clustering and endocytosis. Intracellularly, galectins can participate
      in signaling pathways and modulate biologic responses. These include apoptosis,
      cell differentiation, and cell migration. Thus, a large body of literature
      indicates that galectins play important roles in the immune and inflammatory
      responses through regulating the homeostasis and functions of immune cells. The
      use of mice deficient in individual galectins has provided additional evidence
      for the contributions of these proteins to these responses. Current research
      indicates that galectins play important roles in the development of acute
      inflammation as well as chronic inflammation associated with allergies,
      autoimmune diseases, atherosclerosis, infectious processes, and cancer. Thus,
      recombinant proteins or specific galectin inhibitors may be used as therapeutic
      agents for inflammatory diseases.

PMID- 20146713
TI  - Phosphoinositide 3-kinase and the mammalian target of rapamycin pathways control
      T cell migration.
AB  - The established role for phosphatidylinositol (3,4,5) triphosphate (PI(3,4,5)P3)
      signaling pathways is to regulate cell metabolism. More recently it has emerged
      that PI(3,4,5)P3 signaling via mammalian target of rapamycin and Foxo
      transcription factors also controls lymphocyte trafficking by determining the
      repertoire of adhesion and chemokine receptors expressed by T lymphocytes. In
      quiescent T cells, nonphosphorylated active Foxos maintain expression of KLF2, a
      transcription factor that regulates expression of the chemokine receptors CCR7
      and sphingosine 1 phosphate receptor, and the adhesion receptor CD62L that
      together control T-cell transmigration into secondary lymphoid tissues.
      PI(3,4,5)P3 mediates activation of protein kinase B, which phosphorylates and
      inactivates Foxos, thereby terminating expression of KLF2 and its target genes.
      The correct localization of lymphocytes is essential for effective immune
      responses, and the ability of phosphoinositide 3-kinase and mammalian target of
      rapamycin to regulate expression of chemokine receptors and adhesion molecules
      puts these signaling molecules at the core of the molecular mechanisms that
      control lymphocyte trafficking.

PMID- 20146712
TI  - New insights into T cell biology and T cell-directed therapy for autoimmunity,
      inflammation, and immunosuppression.
AB  - T cell-directed therapies have become mainstays in the management of various
      autoimmune diseases and organ transplantation. The understanding of T cell
      biology has expanded greatly since the development of most agents currently in
      use. Here we discuss important recent discoveries pertaining to T helper cell
      differentiation, lineage commitment, and function. Within this context, we
      examine existing T cell-directed therapies, including new agents being evaluated
      in clinical and preclinical studies. We also use recent findings to speculate on
      novel targets.

PMID- 20146715
TI  - MicroRNAs of the immune system: roles in inflammation and cancer.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by
      binding to complementary target mRNAs and either promoting their decay or
      inhibiting their translation. Most eukaryotic genomes studied encode miRNAs,
      which are processed from longer noncoding transcripts through pathways conserved
      from fungi to plants to animals. miRNAs are now understood to be key mediators of
      developmental transitions in a number of model organisms. With respect to the
      immune system, miRNAs affect all facets of immune system development, from
      hematopoiesis to activation in response to infection during both the innate and
      the adaptive immune response. At the same time, miRNA dysregulation is a central
      event in the development and pathophysiology of a number of cancers of the immune
      system. Here we will discuss our current understanding of this general regulatory
      mechanism, focusing on its involvement in inflammation and in oncogenesis.

PMID- 20146716
TI  - New immune pathways from chronic post-viral lung disease.
AB  - To better understand the immunopathogenesis of chronic inflammatory lung disease,
      we established a mouse model of disease that develops after respiratory viral
      infection. The disease that develops in this model is similar to chronic
      obstructive lung disease in humans. Using this model we have characterized two
      distinct phases in the chronic disease process. The first phase appears at three
      weeks after viral infection and depends on type I interferon-dependent expression
      and then subsequent activation of the high-affinity IgE receptor (FcepsilonRI) on
      conventional lung dendritic cells, which in turn recruit IL-13-producing CD4+ T
      cells to the lower airways. The second phase becomes maximal at seven weeks after
      infection and depends on invariant natural killer T (iNKT) cells and lung
      macrophages. Cellular cross-talk relies on interactions between the semi
      invariant Valpha14Jalpha18 T-cell receptor on lung iNKT cells and CD1d on
      macrophages as well as iNKT cell-derived IL-13 and IL-13 receptor on macrophages.
      These interactions drive macrophages to a pattern of alternative activation and
      overproduction of IL-13. This innate immune axis is also activated in patients
      with chronic obstructive lung disease, as evidenced by increased numbers of iNKT
      cells and IL-13-producing alternatively activated macrophages marked by chitinase
      1 production. Together the findings identify two new immune pathways responsible
      for early and late phases of chronic inflammatory lung disease in experimental
      and clinical settings. These findings extend our understanding of the complex
      mechanisms that underlie chronic obstructive lung disease and provide useful
      targets for diagnosis and therapy of this common disorder.

PMID- 20146717
TI  - Th1 and Th17 cells: adversaries and collaborators.
AB  - Autoreactive effector CD4+ T cells have been associated with the pathogenesis of
      autoimmune disorders. Early studies implicated the interferon (IFN)-gamma
      producing T helper (Th)1 subset of CD4+ cells as the causal agents in the
      pathogenesis of autoimmunity. However, further studies have suggested a more
      complex story. In models thought to be driven by Th1 cells, mice lacking the
      hallmark Th1 cytokine IFN-gamma were not protected but tended to have enhanced
      susceptibility to disease. Identification of the IL-17-producing CD4+ effector
      cell lineage (Th17) has helped shed light on this issue. Th17 effector cells are
      induced in parallel to Th1, and, like Th1, polarized Th17 cells have the capacity
      to cause inflammation and autoimmune disease. This, together with the finding
      that deficiency of the Th17-related cytokine IL-23 but not the Th1-related
      cytokine IL-12 causes resistance, led to the notion that Th17 cells are the chief
      contributors to autoimmune tissue inflammation. Nevertheless, mice lacking IL-17
      are not protected from disease and display elevated numbers of IFN-gamma
      producing CD4+ T cells, and, in some cases, lack of IFN-gamma does confer
      resistance. Recent studies report overlapping as well as differential roles of
      these cells in tissue inflammation, which suggests the existence of a more
      complex relationship between these two effector T-cell subsets than has hitherto
      been suspected. This review will attempt to bring together current information
      regarding interaction, balance, and collaborative potential between the Th1 and
      Th17 effector lineages.

PMID- 20146719
TI  - Cross-presentation of peptides from intracellular pathogens by MHC class I
      molecules.
AB  - Many prokaryotic and eukaryotic parasites multiply in specialized subcellular
      niches in the host cell. The invading microbes hijack key cellular functions to
      establish the intracellular niches but, unlike viruses, do not need the protein
      synthesis machinery of host cells to replicate. Circulating CD8+ T cells provide
      protective immunity by recognizing pathogen-derived peptide major
      histocompatibility complex class I molecules (pMHC I) expressed by infected
      cells. Here, we review studies on the complex and varied pathways that produce
      the appropriate pMHC I as ligands for the CD8+ T cells. We also discuss possible
      explanations for the curious observations that CD8+ T cells are specific for
      fewer pMHC I ligands in parasite infections compared to the diversity of pMHC I
      ligands in viral infections.

PMID- 20146718
TI  - Opportunistic autoimmune disorders: from immunotherapy to immune dysregulation.
AB  - Rapid advances in our understanding of the immune network have led to treatment
      modalities for malignancies and autoimmune diseases based on modulation of the
      immune response. Yet therapeutic modulation has resulted in immune dysregulation
      and opportunistic autoimmune sequelae, despite prescreening efforts in clinical
      trials. This review focuses on recent clinical data on opportunistic autoimmune
      disorders arising from three immunotherapeutic modalities: (1) systemic
      immunomodulators, including interferon-alpha (also used to treat hepatitis C
      patients) and interferon-beta; (2) monoclonal antibodies to CTLA-4 and CD52, and
      (3) hematopoietic stem cell transplantation. Uncategorized predisposing factors
      in these patients include major histocompatibility complex and gender genetics,
      prevalence of different autoimmune diseases, prior chemotherapy, underlying
      disorder (e.g., hepatitis C), and preconditioning regimens as part of organ and
      stem cell transplants. Not unexpectedly, the prevalent autoimmune thyroid disease
      surfaced frequently. Our combination models to study the balance between thyroid
      autoimmunity and tumor immunity upon regulatory T-cell perturbation are briefly
      described.

PMID- 20146721
TI  - Epitope specificity and significance in systemic autoimmune diseases.
AB  - Autoimmune diseases are characterized by self-reactive immune processes mediated
      by B and T cells. These disorders exhibit a spectrum of clinical features that
      range from local or organ specific to systemic diseases. Although a variety of
      putative mechanisms that trigger the loss of tolerance and thus the genesis of
      autoimmunity have been identified, for the most part the precise mechanisms
      remain elusive. Nevertheless, it is widely appreciated that autoantibodies are
      useful both in the diagnosis of autoimmune disorders and as molecular biological
      tools to study cellular processes in which the target antigens are involved.
      Several methods and technologies, including protein fragments, synthetic
      peptides, phage display, or structural analyses have been developed for the
      characterization of the specificity of the autoimmune reactions. The present
      review provides an overview of the autoantibody epitopes in systemic autoimmune
      diseases as they relate to the clinical relevance and applications of certain
      autoepitopes and the technologies that are used to classify and identify them.

PMID- 20146722
TI  - Localization and functional characterization of the human NKCC2 isoforms.
AB  - AIM: Salt reabsorption across the apical membrane of cells in the thick ascending
      limb (TAL) of Henle is primarily mediated by the bumetanide-sensitive
      Na(+)/K(+)/2Cl(-) cotransporter NKCC2. Three full-length splice variants of NKCC2
      (NKCC2B, NKCC2A and NKCC2F) have been described. The NKCC2 isoforms have specific
      localizations and transport characteristics, as assessed for rabbit, rat and
      mouse. In the present study, we aimed to address the localization and transport
      characteristics of the human NKCC2 isoforms. METHODS: RT-PCR, in situ
      hybridization and uptake studies in Xenopus oocytes were performed to
      characterize human NKCC2 isoforms. RESULTS: All three classical NKCC2 isoforms
      were detected in the human kidney; in addition, we found splice variants with
      tandem duplicates of the variable exon 4. Contrary to rodents, in which NKCC2F is
      the most abundant NKCC2 isoform, NKCC2A was the dominant isoform in humans;
      similarly, isoform-specific in situ hybridization showed high expression levels
      of human NKCC2A along the TAL. Compared to NKCC2B and NKCC2F, human NKCC2A had
      the lowest Cl(-) affinity as determined by (86)Rb(+) uptake studies in oocytes.
      All NKCC2 isoforms were more efficiently inhibited by bumetanide than by
      furosemide. A sequence analysis of the amino acids encoded by exon 4 variants
      revealed high similarities between human and rodent NKCC2 isoforms, suggesting
      that differences in ion transport characteristics between species may be related
      to sequence variations outside the highly conserved sequence encoded by exon 4.
      CONCLUSION: The human NKCC2 is an example of how differential splicing forms the
      basis for a diversification of transporter protein function.

PMID- 20146720
TI  - Memory CD8+ T cell differentiation.
AB  - In response to infection or effective vaccination, naive antigen-specific CD8+ T
      cells undergo a dramatic highly orchestrated activation process. Initial
      encounter with an appropriately activated antigen-presenting cell leads to
      blastogenesis and an exponential increase in antigen-specific CD8+ T cell
      numbers. Simultaneously, a dynamic differentiation process occurs, resulting in
      formation of both primary effector and long-lived memory cells. Current findings
      have emphasized the heterogeneity of effector and memory cell populations with
      the description of multiple cellular subsets based on phenotype, function, and
      anatomic location. Yet, only recently have we begun to dissect the underlying
      factors mediating the temporal control of the development of distinct effector
      and memory CD8+ T cell sublineages. In this review we will focus on the
      requirements for mounting an effective CD8+ T cell response and highlight the
      elements regulating the differentiation of effector and memory subsets.

PMID- 20146723
TI  - Pyridoxal-5-phosphate plasma concentrations in children receiving tuberculosis
      chemotherapy including isoniazid.
AB  - AIM: Little is known about pyridoxine nutriture of children treated with
      isoniazid (INH) regimens. This study documents plasma pyridoxal 5'-phosphate
      (PLP) concentrations in children, HIV-infected and HIV-uninfected, receiving INH
      regimens. METHODS: Children from the Western Cape of South Africa hospitalized
      for tuberculosis (TB) management were studied. Plasma PLP concentrations were
      determined on enrolment, 1-month after commencing TB treatment, and again after 4
      month's treatment. The children received a supplement meeting pyridoxine
      requirements. RESULTS: Nineteen HIV-infected and 33 HIV-uninfected children
      received INH (dosage range 4-20 mg/kg) daily. Mean PLP plasma concentrations on
      enrolment were 8.32 (SD 6.75) ng/mL and 11.28 (SD 3.02) ng/mL in HIV-infected and
      HIV-uninfected children, respectively (p = 0.11) and after 4-month's treatment
      6.75 (SD 2.71) ng/mL and 14.76 (SD 7.96) ng/mL (p < 0.001). On enrolment 9 (50%)
      HIV-infected and 5 (15%) HIV-uninfected children (p = 0.016) had suboptimal PLP
      concentrations (<6 ng/mL); after 4-month's treatment 8 (42%) and 2 (6%) (p =
      0.004). CONCLUSION: Plasma PLP concentrations in children treated for TB were low
      on enrolment in HIV-infected and HIV-uninfected children; after 4-month's
      treatment low values were still common in HIV-infected children. Additional
      pyridoxine supplementation of malnourished children treated for tuberculosis is
      advisable, particularly those HIV-infected.

PMID- 20146724
TI  - Determinants of adherence to a single-dose nevirapine regimen for the prevention
      of mother-to-child HIV transmission in Gert Sibande district in South Africa.
AB  - AIM: To identify factors that influence adherence to antiretroviral (ARV)
      prophylaxis by HIV positive mothers participating in the HIV prevention of mother
      to child (PMTCT) programme. METHODS: Post-delivery 815 HIV-infected mothers aged
      18 years and above with babies aged 3-6 months were interviewed in Gert Sibande
      District, Mpumalanga province, South Africa. RESULTS: Eighty five percent of the
      mothers indicated that they had been provided with nevirapine and 78.4% took it
      before or at the onset of labour and infant nevirapine intake was 76.9%. In
      multivariate analysis it was found that women with better PMTCT knowledge had a
      higher perceived confidentiality about HIV status at the health facility. They
      had a term delivery and those who had told their partner about nevirapine had a
      higher maternal nevirapine adherence. Women who had also told their partner about
      nevirapine, whose partner was asked for an HIV test and those who knew the HIV
      status of their infant had higher infant nevirapine adherence. CONCLUSION:
      Adherence to maternal and infant ARV prophylaxis was found to be sub-optimal.
      Health services delivery factors, male involvement, communication and social
      support contribute to adherence to ARV prophylaxis in this largely rural setting
      in South Africa.

PMID- 20146725
TI  - Influenza A/H1N1 (2009) infection in pregnancy--an Asian perspective.
AB  - OBJECTIVE: To describe the characteristics of an obstetric population with
      influenza A/H1N1 (2009) infection, with a focus on the need for hospitalisation
      and complications. DESIGN: Cohort study. SETTING: Tertiary referral centre.
      POPULATION: Two hundred and eleven pregnant women with influenza A/H1N1 (2009)
      infection diagnosed by nasopharyngeal swab polymerase chain reaction (PCR).
      METHODS: Obstetric patients presenting to our centre were recruited and followed
      up. Data collected included demographic and clinical information. MAIN OUTCOME
      MEASURES: H1N1 and pregnancy complications, and hospitalisation needs. RESULTS:
      The median age of the cohort was 29.0 years (range 16-42 years), the median
      gestation at referral was 23.0 weeks (range 4-38 weeks), the median time interval
      between illness onset and presentation was 2.0 days (range 1-7 days), and the
      median time interval between illness onset and commencement of oseltamivir was
      2.0 days (range 1-11 days). Hospital admission was significantly associated with
      the presence of co-morbidity (OR 4.14, 95% CI 1.82-9.37, P = 0.0001),
      breathlessness (OR 5.2, 95% CI 2.19-12.41, P = 0.0003) and sore throat (OR 0.35,
      95% CI 0.16-0.73, P = 0.005). There were two cases of pneumonia complicating H1N1
      infection, but no mortality. Nine cases developed pregnancy complications. All
      women recovered. CONCLUSIONS: The need for hospitalisation was significantly
      associated with breathlessness and co-morbidity. There was minimal morbidity and
      no mortality observed. We attribute this to early presentation, diagnosis and
      treatment.

PMID- 20146726
TI  - Localization of muscarinic receptors M1R, M2R and M3R in the human colon.
AB  - BACKGROUND: Muscarinic acetylcholine receptors (MR) are involved in multiple
      intestinal reflexes. The cellular localization of subtypes of MRs within enteric
      circuits mediating muscle and mucosal reflexes remains to be demonstrated. This
      study aimed to localize the three functionally significant subtypes of MRs in
      human colon. METHODS: Reverse transcriptase-PCR was used to determine expression
      levels of muscarinic receptor subtype (MRs) M1Rs, M2Rs and M3Rs in human colon.
      Indirect immunofluorescence and confocal microscopy was used to localize MRs in
      cryostat-cut sections of human colon. Sections were double labeled for multiple
      cellular and neurochemical markers. Western blotting was used to confirm
      specificity of the muscarinic antisera used. KEY RESULTS: All three MR subtypes
      were expressed in human colon. Immunoreactivity (IR) for M2Rs and M3Rs was most
      abundant in circular and longitudinal muscle. M1R-IR was most abundant on
      myenteric and submucosal nerve cells, both cholinergic and nitrergic. M3R-IR was
      also present on populations on myenteric nerve cell bodies. Immunoreactivity for
      all three receptors was present on nerve fibers in the circular muscle.
      CONCLUSIONS & INFERENCES: In the human colon, subtypes of MRs were present on
      multiple cell types within the enteric circuits underlying motility, secretory
      and vasoactive reflexes. The cellular distribution for MRs found in this study
      agrees with data from functional studies, providing insight into the role MRs
      have in mediating enteric cholinergic neurotransmission.

PMID- 20146727
TI  - A 5-HT(4)-receptor activation-induced neural plasticity enhances in vivo
      reconstructs of enteric nerve circuit insult.
AB  - BACKGROUND: It was recently reported that some 5-HT(4)-receptor agonists
      increased neuronal numbers and length of neurites in enteric neurons developing
      in vitro from immunoselected neural crest-derived precursors. We aimed to explore
      a novel approach in vivo to reconstruct the enteric neural circuitry that
      mediates a fundamental distal gut reflex. METHODS: The neural circuit insult was
      performed in guinea pigs by rectal transection and subsequent end-to-end one
      layer anastomosis. A 5-HT(4)-receptor agonist, mosapride citrate (10-100 micromol
      L(-1)) (applied for a patent) was applied locally at the anastomotic site. KEY
      RESULTS: Mosapride promoted the regeneration of the neural circuit in the
      impaired myenteric plexus and the recovery of the defecation reflex in the distal
      gut. Furthermore, mosapride generated neurofilament (NF)-, 5-HT(4)-receptor- and
      5-bromo-2'-deoxyuridine (BrdU)-positive cells and surprisingly formed neural
      network in the newly formed granulation tissue at the anastomotic site 2 weeks
      after enteric nerve circuit insult. Possible neural stem cell markers, anti
      distal less homeobox 2 (DLX2)- and p75-positive and NF-positive cells increased
      during the same time period. All actions by mosapride were inhibited by the
      specific 5-HT(4)-receptor antagonist, GR113808 (10 micromol L(-1)). CONCLUSIONS &
      INFERENCES: These results indicate that activation of enteric neural 5-HT(4)
      receptors promotes reconstruction of an enteric neural circuit leading to the
      recovery of the defecation reflex in the distal gut, and that this reconstruction
      involves possibly neural stem cells. These findings indicate that treatment with
      5-HT(4) agonists could be a novel therapy for generating new enteric neurons to
      rescue aganglionic gut disorders.

PMID- 20146728
TI  - Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper.
AB  - BACKGROUND: First-generation H(1)-antihistamines obtained without prescription
      are the most frequent form of self-medication for allergic diseases, coughs and
      colds and insomnia even though they have potentially dangerous unwanted effects
      which are not recognized by the general public. AIMS: To increase consumer
      protection by bringing to the attention of regulatory authorities, physicians and
      the general public the potential dangers of the indiscriminate use first
      generation H(1)-antihistamines purchased over-the counter in the absence of
      appropriate medical supervision. METHODS: A GA(2)LEN (Global Allergy and Asthma
      European Network) task force assessed the unwanted side-effects and potential
      dangers of first-generation H1-antihistamines by reviewing the literature
      (Medline and Embase) and performing a media audit of US coverage from 1996 to
      2008 of accidents and fatal adverse events in which these drugs were implicated.
      RESULTS: First-generation H(1)-antihistamines, all of which are sedating, are
      generally regarded as safe by laypersons and healthcare professionals because of
      their long-standing use. However, they reduce rapid eye movement (REM)-sleep,
      impair learning and reduce work efficiency. They are implicated in civil
      aviation, motor vehicle and boating accidents, deaths as a result of accidental
      or intentional overdosing in infants and young children and suicide in teenagers
      and adults. Some exhibit cardiotoxicity in overdose. CONCLUSIONS: This review
      raises the issue of better consumer protection by recommending that older first
      generation H(1)-antihistamines should no longer be available over-the-counter as
      prescription- free drugs for self-medication of allergic and other diseases now
      that newer second- generation nonsedating H(1)-antihistamines with superior
      risk/benefit ratios are widely available at competitive prices.

PMID- 20146729
TI  - IgE to peanut allergen components: relation to peanut symptoms and pollen
      sensitization in 8-year-olds.
AB  - BACKGROUND: Allergen-specific IgE testing is often performed with crude peanut
      extract, but the results may be difficult to interpret because of cross-reactions
      between peanut and other plant allergens. The aim was to investigate IgE
      reactivity to peanut allergen components in children from a birch-rich region in
      relation to pollen sensitization and peanut symptoms. METHODS: From a birth
      cohort, clinical parameters were obtained through questionnaires and IgE antibody
      levels to peanut and birch pollen were measured. Different peanut/birch
      sensitization phenotypes were defined among 200 selected children. IgE reactivity
      to peanut and pollen allergen components was analysed using microarray technique.
      RESULTS: Peanut symptoms were reported in 87% of the children with IgE reactivity
      to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 (n = 46) vs 17%
      of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 (n = 23), P
      < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3
      reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more
      often reported peanut symptoms than children with IgE only to Ara h 2 (97%vs 70%,
      P = 0.016), particularly respiratory symptoms (50%vs 9%, P = 0.002). CONCLUSIONS:
      IgE analysis to peanut allergen components may be used to distinguish between
      peanut-sensitized individuals at risk of severe symptoms and those likely to have
      milder or no symptoms to peanut if sensitized to pollen allergens and their
      peanut homologue allergens.

PMID- 20146730
TI  - Lifestyle and parental allergen sensitization are reflected in the intrauterine
      environment at gene expression level.
AB  - BACKGROUND: Environmental factors, including the intrauterine environment, can
      influence the risk of allergy development. In the present study, we investigated
      whether lifestyle and parental allergen sensitization status are reflected at
      gene expression level in the intrauterine environment. METHODS:   mRNA expression
      of 17 genes was determined by means of quantitative real-time PCR in term
      placenta of 36 families participating in the ALADDIN study (Assessment of
      Lifestyle and Allergic Disease During Infancy). Data were analysed using a linear
      regression model to estimate the influence of lifestyle and parental allergen
      sensitization on the relative mRNA expression levels. Immunohistochemistry on
      placenta biopsies was used to verify protein expression. RESULTS: Significant
      differences in mRNA expression levels were detected at the foetal side of the
      placenta, where CD14 was expressed at higher levels in placentas from families
      living on a farm compared to not living on a farm, and IL-12(p40) was expressed
      at lower levels when the father was sensitized compared to nonsensitized. At the
      maternal side of the placenta, higher expression of STAT4 and lower expression of
      GATA3 were detected in families with sensitized compared to nonsensitized
      mothers, and IL-12(p40) was lower expressed when the families were living on a
      farm compared to not living on a farm. Immunohistochemistry performed for STAT4
      and GATA3 showed that protein and mRNA levels correlated well. CONCLUSION: Living
      on a farm and parental allergen sensitization are reflected in the intrauterine
      environment at the gene expression level.

PMID- 20146731
TI  - Improving clinician-patient communication in asthma: the HARP project.

PMID- 20146732
TI  - Differences in the soluble HLA-G blood serum concentration levels in patients
      with ovarian cancer and ovarian and deep endometriosis.
AB  - PROBLEM: The relationship between endometriosis and cancer has been widely
      discussed in the literature but is still not well clarified. Perhaps
      significantly, soluble human leukocyte antigen-G (sHLA-G) has been identified in
      the microenvironment of both ovarian cancer and endometrioma. The aim of this
      study has been to evaluate the sHLA-G levels in the blood sera of women with deep
      endometriosis and ovarian endometrioma over the course of the menstrual cycle and
      to compare to the levels of sHLA-G in the blood sera of women with ovarian
      cancer. METHOD OF STUDY: In our study, we examined the blood sera obtained from
      123 patients operated on because of ovarian cancer (65 cases), ovarian
      endometrioma (30 cases), and deep endometriosis (28 cases). We decided to compare
      the levels of sHLA-G in patients with endometriosis to those found in patients
      with ovarian cancer with respect to the menstrual cycle phases. The sHLA-G
      concentration level was measured by enzyme-linked immunosorbent assay kit.
      RESULTS: The level of sHLA-G concentration in the blood serum of patients with
      deep endometriosis fluctuates over the course of the menstrual cycle, and during
      the proliferative and secretory phases, it remains at a high level comparable to
      that found in patients with ovarian cancer. By contrast, the level of sHLA-G
      concentration in the blood serum of patients with ovarian endometrioma fluctuates
      minimally over the course of the different menstrual cycle phases and, as in
      patients with ovarian cancer, it remains at high level during the proliferative
      phase. CONCLUSION: sHLA-G blood serum concentration levels would seem to provide
      important information regarding the degree of immune system regulation
      disturbance in both ectopic endometrial cells and the cancer cell suppressive
      microenvironment.

PMID- 20146734
TI  - High level of primary drug resistance in Mali.
AB  - BACKGROUND: As access to antiretroviral drugs increases in developing countries,
      it will become increasingly important to monitor the emergence of resistance and
      to define the molecular pathways involved to identify optimal therapeutic
      regimens. METHODS: We performed genotypic resistance testing on plasma obtained
      from 101 HIV-infected treatment-naive individuals from Mali. Genotyping was
      carried out using the Virco protocols and HXB2 was used as the reference strain.
      RESULTS: CRF02_AG was the most common subtype, present in 71.3% of our patient
      population. Other subtypes included B, C, G, CRF06_CPX, CRF09_CPX, CRF01_AE,
      A2/CRF16_A2D, A1 and CRF13_CPX. A total of 9.9% [95% confidence interval (CI) 6.9
      12.9%] of patients had at least one resistance mutation. The prevalences of
      mutations conferring resistance to nucleoside reverse transcriptase inhibitors
      (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease
      inhibitors (PIs) were 5% (95% CI 0.7-9.2%), 6% (95% CI 1.3-10.6%) and 0%,
      respectively. The most frequent mutations were T215A/Y for NRTIs and K103N/T for
      NNRTIs. One patient harboured three NRTI resistance mutations and one NNRTI
      mutation. This is the first reported case of multi-drug-resistant viral
      transmission in Mali. Polymorphisms at protease codons 10I/V and 33F potentially
      associated with resistance were observed in 18.8% and 1% of patients,
      respectively. Several polymorphisms in the C-terminal domain of reverse
      transcriptase were observed: A371V (in 63.4% of patients), G335D (76.2%), E399D
      (10.9%) and G333E (1%). CONCLUSION: Primary resistance was seen in 9.9% of
      subjects, which is higher than previously reported in Mali. Taking into
      consideration other polymorphisms in protease such as L10I/V and 33F, primary
      resistance could reach 28.7% (95% CI 19.9-37.5%). Our study reflects the need to
      monitor the evolution of resistance on a regular basis and trends of transmitted
      resistance.

PMID- 20146733
TI  - Upper gastrointestinal endoscopic findings in the era of highly active
      antiretroviral therapy.
AB  - BACKGROUND: The current literature suggests that there has been a decrease in
      opportunistic diseases among HIV-infected patients since the widespread
      introduction of highly active antiretroviral therapy (HAART) in 1995. OBJECTIVES:
      The aim of the study was to investigate the impact of HAART and CD4 lymphocyte
      count on diseases of the upper gastrointestinal (UGI) tract, digestive symptoms,
      and endoscopic and histological observations. METHODS: A review of 706 HIV
      infected patients who underwent GI endoscopy was undertaken. The cohort was
      divided into three groups: group 1 (G1), pre-HAART, consisting of 239 patients
      who underwent endoscopy between January 1991 and December 1994; group 2 (G2),
      early HAART, consisting of 238 patients who underwent endoscopy between January
      1999 and December 2002; and group 3 (G3), recent HAART, consisting of 229
      patients who underwent endoscopy between January 2005 and December 2008.
      Parameters studied included age, gender, opportunistic chemoprophylaxis,
      antiretroviral therapies, CD4 cell counts, symptoms, observations at the first
      UGI endoscopy and histology. RESULTS: When G1, G2 and G3 were compared,
      significant increases were seen over time in the following parameters: the
      percentage of women, the mean CD4 cell count, and the frequencies of reflux
      symptoms, gastroesophageal reflux disease (GERD), inflammatory gastropathy,
      gastric ulcer and Helicobacter pylori (HP) infection. Significant decreases were
      seen in the frequencies of the administration of anti-opportunistic infection
      prophylaxis, odynophagia/dysphagia, acute/chronic diarrhoea, candida
      oesophagitis, nonspecific oesophageal ulcer and Kaposi sarcoma. No significant
      change was observed in the other parameters, i.e. digestive bleeding, duodenal
      ulcer and inflammatory duodenopathy. CONCLUSION: These results suggest a
      correlation between the improvement of immunity as a result of more efficient
      antiviral therapy and the decrease in the frequency of digestive diseases in
      AIDS, mainly opportunistic pathologies. However, HP infection, reflux symptoms
      and GERD have increased in the HAART era.

PMID- 20146735
TI  - Prevention of mother-to-child transmission of HIV in Denmark, 1994-2008.
AB  - OBJECTIVES: The aim of this study was to describe trends in the management of
      pregnancies in HIV-infected women and their outcomes over a 14-year period in
      Denmark on a national basis. METHODS: The study was a retrospective cohort study
      of all HIV-infected women in Denmark giving birth to one or more children between
      1 June 1994 and 30 June 2008. RESULTS: We identified 210 HIV-infected women with
      255 pregnancies, ranging from 7 per year in 1995 to 39 per year in 2006. Thirty
      per cent of the women were Caucasian and 51% were Black African. Knowledge of HIV
      status before pregnancy increased from 8% (four of 49) in 1994-1999 to 80% (164
      of 206) in 2000-2008. Only 29% (53 of 183) of the women chose to consult an
      infectious disease specialist when planning pregnancy, while 14% (27 of 199)
      received assistance with fertility. The proportion of women on antiretroviral
      therapy (ART) increased from 76% (37 of 49) in 1994-1999 to 98% (201 of 206) in
      2000-2008. Vaginal deliveries ranged from 0 in 2003 to 35% of pregnancies in
      2007. Mother-to-child transmission (MTCT) of HIV decreased from 10.4% in 1994
      1999 to 0.5% in 2000-2008. All women giving birth to an HIV-positive child were
      diagnosed with HIV during or after delivery and did not receive prophylactic ART.
      CONCLUSIONS: The annual number of HIV pregnancies increased fivefold during this
      14-year period and substantial changes in pregnancy management were seen. No
      woman treated according to the national guidelines, i.e. ART before week 22,
      intravenous zidovudine (ZDV) during labour, neonatal ZDV for 4 to 6 weeks and no
      breastfeeding, transmitted HIV to her child.

PMID- 20146737
TI  - Epidemiology of invasive Streptococcus pyogenes disease in Germany during 2003
      2007.
AB  - A nationwide laboratory-based surveillance study of invasive Streptococcus
      pyogenes infections was conducted in Germany. Invasive isolates (n=586) were
      obtained between 2003 and 2007. Most isolates were obtained from blood (53.9%) or
      skin lesions (17.6%). The most common emm types were emm 1 (30.5%), emm 28
      (18.3%) and emm 3 (9.6%). Overall, speA was positive in 45.9%, speC in 44.7% and
      ssa in 14.8% of isolates. SpeA was common in emm type 1 (100%) and emm type 3
      (96.4%), whereas speC was often observed in emm type 28 (93.5%). The most
      frequent clinical manifestations included sepsis (40.1%), necrotizing fasciitis
      (20.8%) and streptococcal toxic shock syndrome (16.6%). All isolates were
      susceptible to penicillin G, cefotaxime and levofloxacin. Tetracycline shows the
      highest rate of resistant or intermediate isolates with 11.6%, followed by
      clarithromycin (5.5%) and clindamycin (1.2%). The most prominent trend is the
      reduction of tetracycline-nonsusceptible isolates from 18.6% in 2003 to 8.9% in
      2007.

PMID- 20146736
TI  - Trends over calendar time in antiretroviral treatment success and failure in HIV
      clinic populations.
AB  - OBJECTIVE: Effective antiretroviral therapy (ART) has transformed the care of
      people with HIV, but it is important to monitor time trends in indicators of
      treatment success and antic future changes. METHODS: We assessed time trends from
      2000 to 2007 in several indicators of treatment success in the UK Collaborative
      HIV Cohort (CHIC) Study, and using national HIV data from the Health Protection
      Agency (HPA) we developed a model to project future trends. RESULTS: The
      proportion of patients on ART with a viral load <50 HIV-1 RNA copies/mL increased
      from 62% in 2000 to 84% in 2007, and the proportion of all patients with a CD4
      count <200 cells/microL decreased from 21% to 10%. During this period, the number
      of patients who experienced extensive triple class failure (ETCF) rose from 147
      (0.9%) to 1771 (3.9%). The number who experienced such ETCF and had a current
      viral load >50 copies/mL rose fromz 118 (0.7%) to 857 (1.9%). Projections to 2012
      suggest sustained high levels of success, with a continued increase in the number
      of patients who have failed multiple drugs but a relatively stable number of such
      patients experiencing viral loads >50 copies/mL. Numbers of deaths are projected
      to remain low. CONCLUSIONS: There have been continued improvements in key
      indicators of success in patients with HIV from 2000 to 2007. Although the number
      of patients who have ETCF is projected to rise in the future, the number of such
      patients with viral loads >50 copies/mL is not projected to increase up to 2012.
      New drugs may be needed in future to sustain these positive trends.

PMID- 20146739
TI  - Participation in intellectual disability research: a review of 20 years of
      studies.
AB  - BACKGROUND: Researchers have noted difficulties in attracting adequate numbers of
      participants with intellectual disabilities (ID) to their studies. METHODS: This
      study was a review of participation by adults with ID in research conducted in
      South Eastern Ontario over a 20-year period (1987-2006). Original research
      studies were identified by local investigators and then reviewed for inclusion
      and exclusion criteria. The report of each study was then reviewed by three
      reviewers and key information was extracted. The extent of study participation
      was calculated using three methods and compared along with key design
      characteristics. RESULTS: Nine studies met all inclusion/exclusion criteria and
      provided sufficient data to calculate participation. Among the studies there was
      a variety of purposes, research designs and recruitment strategies. Using the
      participant/approached calculation, participation varied between 41.8% and 100%.
      Higher participation was observed in studies where investigators had direct
      access to participants, the data collection was non-invasive and consent was
      required from substitute decision-makers only. There was no clear trend of
      increasing or decreasing participation over time. CONCLUSIONS: Researchers
      seeking the participation of adults with ID in their studies must incorporate
      factors influencing participation into study designs to ensure robust results and
      effective use of research resources.

PMID- 20146740
TI  - The development of the QUALITRA-ID: a user-orientated interview to assess the
      quality of care and service trajectories for intellectually disabled persons.
AB  - BACKGROUND: Care and service trajectories for people with intellectual
      disabilities (ID) are routes within the healthcare delivery system that consist
      of all the steps that people with ID and their families have to take in order to
      realise the needed care and services. In contrast to the growing system
      orientated knowledge concerning quality of care delivered through collaborative
      relationships between care providers, specific user-orientated knowledge
      regarding the quality of care and service trajectories is largely lacking. AIM:
      This article aims to describe the development of the QUALITRA-ID; a user
      orientated interview concerning the quality of care and service trajectories for
      people with ID. METHODS: First, the phenomenon 'care and service trajectories' is
      conceptualised on the basis of document analysis and semi-structured interviews
      with key informants in the field of health care for people with ID. Second, the
      quality of care and service trajectories is operationalized by means of eight
      focus group discussions with intellectually disabled persons and their
      parents/relatives and a review of the literature. Third, the QUALITRA-ID is
      constructed using the results of the conceptualization and operationalization of
      the phenomenon. Fourth, the QUALITRA-ID is refined in two stages that were
      concerned with examining the feasibility, understandability and completeness of
      the QUALITRA-ID. The second stage was also concerned with the first quality
      assessment among people with ID. RESULTS: The final result is a 24-item QUALITRA
      ID consisting of a personal conversation and a closed-ended part.

PMID- 20146741
TI  - Parenting stress and coping styles in mothers and fathers of pre-school children
      with autism and Down syndrome.
AB  - BACKGROUND: The study examined the profile of stress in mothers and fathers of
      preschool children with autism, Down syndrome and typically developing children.
      A further aim was to assess the association between parenting stress and coping
      style. METHODS: A total of 162 parents were examined using Holroyd's 66-item
      short form of Questionnaire of Resources and Stress for Families with Chronically
      Ill or Handicapped Members and the Coping Inventory for Stressful Situations by
      Endler and Parker. RESULTS AND CONCLUSIONS: The results indicated a higher level
      of stress in parents of children with autism. Additionally, an interaction effect
      was revealed between child diagnostic group and parent's gender for two scales of
      parenting stress: dependency and management and limits of family opportunities.
      Mothers of children with autism scored higher than fathers in parental stress; no
      such differences were found in the group of parents of children with Down
      syndrome and typically developing children. It was also found that parents of
      children with autism differed from parents of typically developing children in
      social diversion coping. Emotion-oriented coping was the predictor for parental
      stress in the samples of parents of children with autism and Down syndrome, and
      task-oriented coping was the predictor of parental stress in the sample of
      parents of typically developing children. The results strongly supported earlier
      findings on parenting stress in parents of children with autism. They also shed
      interesting light on the relationship between coping styles and parental stress.

PMID- 20146742
TI  - Expressive language in male adolescents with fragile X syndrome with and without
      comorbid autism.
AB  - BACKGROUND: Approximately one-quarter of individuals with fragile X syndrome
      (FXS) meet diagnostic criteria for autism; however, it is unclear whether
      individuals with comorbid FXS and autism are simply more severely affected than
      their peers with only FXS or whether they have qualitatively different profiles
      of behavioural impairments. To address this issue, variation in the FXS
      linguistic phenotype was examined in males with FXS with and without autism. The
      syndrome-specificity of the expressive language impairment of both groups of
      those with FXS was assessed in relation to Down syndrome. The extent to which
      different language sampling contexts affected expressive language in each
      diagnostic group was also examined. METHOD: Spontaneous language samples were
      collected from male adolescents with FXS without autism (n = 20), comorbid FXS
      and autism (n = 8), and Down syndrome (n = 16). Syntactic complexity (indexed by
      mean length of utterance), expressive vocabulary (indexed by lexical diversity),
      talkativeness, fluency and intelligibility were assessed in two contexts:
      conversation and narration. Groups were matched on non-verbal IQ, non-verbal
      mental age and chronological age to allow the assessment of relative strengths
      and weaknesses across language variables. RESULTS: Males with comorbid FXS and
      autism were less intelligible than males with only FXS; no other differences
      between these two groups were found. Participants' performance differed across
      contexts for syntactic complexity, lexical diversity, talkativeness and fluency.
      CONCLUSIONS: These findings contribute to existing research on the behavioural
      profiles of individuals with FXS or FXS with autism who have low cognitive
      abilities. Although individuals with comorbid FXS and autism may be, as a group,
      more impaired than those with only FXS, data from this small sample of males with
      comorbid FXS and autism with low IQs suggest that their relative strengths and
      weaknesses in spontaneous expressive language are largely comparable and not
      differentially affected by the context in which their talk occurs.

PMID- 20146743
TI  - Multicopy suppression of oxidant-sensitive eos1 mutation by IZH2 in Saccharomyces
      cerevisiae and the involvement of Eos1 in zinc homeostasis.
AB  - EOS1 is required for tolerance to oxidative stress in Saccharomyces cerevisiae;
      mutants are defective in the gene sensitive to hydrogen peroxide and tolerant to
      tunicamycin. To clarify the function of Eos1, we screened yeast genomic DNA
      libraries for heterologous genes that, when overexpressed from a plasmid, can
      suppress the hydrogen peroxide-sensitive eos1 mutation. We identified one such
      gene, IZH2, which has previously been reported to be a Zap1-regulated gene.
      However, the EOS1 and IZH2 genes do not themselves appear to be functionally
      interchangeable. Double disruption of the EOS1 and IZH2 genes yielded a slow
      growth phenotype, suggesting that the two proteins are involved in related
      cellular processes. DNA microarray analysis revealed decreased expression of Zap1
      regulated genes in the eos1-deletion mutant (Deltaeos1). Thus, it is likely that
      Eos1 is involved in zinc homeostasis.

PMID- 20146744
TI  - Effect of ethanol on fluxes of water and protons across the plasma membrane of
      Saccharomyces cerevisiae.
AB  - Plasma membrane integrity, ability to transport substrates and maintenance of
      homeostasis represent obligatory requirements for efficient ethanol production by
      Saccharomyces cerevisiae. The effect of ethanol on water diffusion through the
      bilayer and on mediated water movements was evaluated by stopped flow
      spectroscopy. Ethanol stimulated water diffusion and inhibited mediated water
      transport. In a strain overexpressing AQY1, the activation energy for water
      transport increased progressively (from 5.9 to 12.7 kcal mol(-1)) for increasing
      ethanol concentrations (up to 12% v/v), indicating that mediated water transport
      lost importance as compared with water diffusion through the bilayer. The effect
      of ethanol on proton movements (inward by passive diffusion and outward through
      the PMA1 H(+)-ATPase) was evaluated by measuring the rate of extracellular
      alcalinization and acidification of unbuffered cell suspensions at different
      temperatures. Above 10% ethanol, H(+) diffusion was strongly increased at 30
      degrees C, but no effect was observed at 20 degrees C up to 12%, indicating the
      existence of a threshold above which ethanol has a marked effect. On H(+)
      extrusion, ethanol had no effect at 20 degrees C, but induced a monotonous
      decrease at higher temperatures. Our results support the view that above a
      threshold of ethanol concentration, the membrane structure is disrupted, becoming
      very leaky to H(+).

PMID- 20146745
TI  - Application of real-time PCR in Ghana, a Buruli ulcer-endemic country, confirms
      the presence of Mycobacterium ulcerans in the environment.
AB  - This study reports the first successful application of real-time PCR for the
      detection of Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), in
      Ghana, a BU-endemic country. Environmental samples and organs of small mammals
      were analyzed. The real-time PCR assays confirmed the presence of M. ulcerans in
      a water sample collected in a BU-endemic village in the Ashanti Region.

PMID- 20146746
TI  - Two mobile Pectobacterium atrosepticum prophages modulate virulence.
AB  - The Pectobacterium atrosepticum strain SCRI1043 genome contains two complete
      prophage sequences. One, ECA41, is Mu-like and is able to integrate into, and
      excise from, various genomic locations. The other, ECA29, is a P2 family
      prophage, and is also able to excise from the genome. Excision of both prophages
      is rare and we were unable to induce lysis of cultures. Deletion of the entire
      prophages, both separately and in combination, did not affect the growth rate or
      the secretion of plant cell wall-degrading enzymes, but swimming motility was
      decreased. The virulence of prophage deletion strains in the potato host was
      decreased.

PMID- 20146747
TI  - Bicyclic compounds repress membrane vesicle production and Pseudomonas quinolone
      signal synthesis in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa secretes membrane vesicles (MVs) that deliver several
      virulence factors as a cargo. We found that indole and its derivative compounds,
      including 4-hydroxyindole, 5-hydroxyindole, 6-hydroxyindole and isatin, repress
      MV production significantly. These compounds also repressed the synthesis of
      Pseudomonas quinolone signal (PQS), which is one of the quorum-sensing signals
      that upregulate virulence gene expression and positively control MV production.
      Moreover, we showed that other bicyclic compounds, including 1-naphthol, 2
      naphthol, 2,3-dihydroxynaphthalene, 1-aminonaphthalene and 8-quinolinol,
      significantly repress MV production and PQS synthesis. In conclusion, we provide
      new information about the chemical structures that inhibit P. aeruginosa
      virulence.

PMID- 20146748
TI  - The complexity of the 'simple' two-component system KdpD/KdpE in Escherichia
      coli.
AB  - The KdpD/KdpE two-component system of Escherichia coli activates the expression
      of the kdpFABC operon encoding the high-affinity K(+) uptake system KdpFABC in
      response to K(+) limitation or salt stress. Earlier, it was proposed that the
      histidine kinase KdpD is a turgor sensor; recent studies suggest that KdpD
      integrates three chemical stimuli from the cytoplasm. The histidine kinase KdpD
      contains several structural features and subdomains that are important for
      stimulus perception, modulation of the kinase to phosphatase ratio, and
      signaling. The response regulator KdpE receives the phosphoryl group from KdpD
      and induces kdpFABC transcription. The three-dimensional structure of the
      receiver domain was resolved, providing insights into the activation mechanism of
      this transcriptional regulator. Two accessory components, the universal stress
      protein UspC and the phosphotransferase system component IIA(Ntr), are known to
      interact with KdpD, allowing the modulation of kdpFABC expression under certain
      physiological conditions. Here, we will discuss the complexity of a 'simple' two
      component system and its interconnectivity with metabolism and the general stress
      response.

PMID- 20146749
TI  - So similar, yet so different: uncovering distinctive features in the genomes of
      Salmonella enterica serovars Typhimurium and Typhi.
AB  - Salmonella enterica represents a major human and animal pathogen. Many S.
      enterica genomes have been completed and many more genome sequencing projects are
      underway, constituting an excellent resource for comparative genome analysis
      studies leading to a better understanding of bacterial evolution and
      pathogenesis. Salmonella enterica serovar Typhimurium and Typhi are the best
      characterized serovars, with the first being involved in localized
      gastroenteritis in many hosts and the latter causing a systemic human-specific
      disease. Here, we summarize the major genetic differences between the two
      different serovars. We detail the divergent repertoires of the virulence factors
      responsible for the pathogenesis of the organisms and that ultimately result in
      the distinct clinical outcomes of infection. This comparative genomic overview
      highlights hypotheses for future investigations on S. enterica pathogenesis and
      the basis of host specificity.

PMID- 20146750
TI  - In vitro evaluation of the prebiotic properties of almond skins (Amygdalus
      communis L.).
AB  - In this study we investigated the potential prebiotic effect of natural (NS) and
      blanched (BS) almond skins, the latter being a byproduct of the almond-processing
      industry. A full model of the gastrointestinal tract, including in vitro gastric
      and duodenal digestion, followed by colonic fermentation using mixed faecal
      bacterial cultures, was used. Both NS and BS significantly increased the
      population of bifidobacteria and Clostridium coccoides/Eubacterium rectale group,
      resulting in a prebiotic index (3.2 for BS and 3.3 for NS) that compared well
      with the commercial prebiotic fructo-oligosaccharides (4.2) at a 24-h incubation.
      No significant differences in the proportion of gut bacteria groups and in short
      chain fatty acid production were detected between NS and BS, showing that
      polyphenols present in almond skins did not affect bacterial fermentation. In
      conclusion, we have shown that dietary fibre from almond skins altered the
      composition of gut bacteria and almond skins resulting from industrial blanching
      could be used as potential prebiotics.

PMID- 20146751
TI  - Developmental origins of disruptive behaviour problems: the 'original sin'
      hypothesis, epigenetics and their consequences for prevention.
AB  - This paper reviews publications on developmental trajectories of disruptive
      behaviour (DB) problems (aggression, opposition-defiance, rule breaking, and
      stealing-vandalism) over the past decade. Prior to these studies two theoretical
      models had strongly influenced research on DB: social learning and disease onset.
      According to these developmental perspectives, children learn DB from their
      environment and onset of the disease is triggered by accumulated exposition to
      disruptive models in the environment, including the media. Most of the evidence
      came from studies of school age children and adolescents. Longitudinal studies
      tracing developmental trajectories of DB from early childhood onwards suggest an
      inversed developmental process. DB are universal during early childhood. With
      age, children learn socially acceptable behaviours from interactions with their
      environment. A 'disease' status is given to children who fail to learn the
      socially acceptable behaviours. The mechanisms that lead to deficits in using
      socially accepted behaviours are strongly intergenerational, based on complex
      genetic and environmental contributions, including epigenetic mechanisms.
      Prevention of these deficits requires early, intensive and long-term support to
      parents and child. Newly discovered epigenetic mechanisms suggest that intensive
      perinatal interventions will have impacts on numerous aspects of physical and
      mental health, including DB. This review also concludes that: a) subtypes of
      disruptive behaviours should not be aggregated because they have different
      developmental trajectories and require specific corrective interventions; b) the
      overt-covert and destructive-nondestructive dimensions appear the most useful to
      create DB subtypes; c) overt DB onset before covert DB because the latter require
      more brain maturation; d) DB subtype taxonomies are more useful for clinicians
      than developmental taxonomies because the latter are post mortem diagnoses and
      clinicians' retrospective information is unreliable; e) we need large-scale
      collaborative preventive experimental interventions starting during early
      pregnancy to advance knowledge on causes and prevention of DB problems.

PMID- 20146752
TI  - Use of SAG-M-suspended red cell concentrate in large volume transfusion
      associated with cardiac surgery in neonates and infants: a retrospective audit.

PMID- 20146753
TI  - The effect of rowing on endothelial function and insulin action in healthy
      controls and in patients with type 2 diabetes.
AB  - Patients with type 2 diabetes (T2DM) have an increased risk for cardiovascular
      disease. We examined the effects of 8 weeks of home-based rowing training (heart
      rate corresponding to 65-70% of VO(2 peak) ) on endothelial function and glucose
      clearance (local and systemic effects) in male subjects with T2DM (n=9) and
      matched controls (n=8). Before and after training (30 min every other day), all
      subjects underwent sequential graded brachial artery infusions of non-insulin
      vasodilators (acetylcholine; sodium nitroprusside; adenosine). Forearm blood flow
      was improved by training in controls (without and with insulin: P=0.003 and 0.05,
      respectively) but not in subjects with T2DM. Likewise, whole body glucose
      clearance increased in response to training in controls (P=0.05) but not in T2DM.
      However, in both groups, the capacity for local forearm glucose extraction
      (controls: P=0.001; T2DM: P=0.002) and clearance (controls: P<0.001; T2DM:
      P=0.01) were positively affected by exercise. While the subjects with T2DM did
      not respond to the same degree as controls to 8 weeks of home-based exercise,
      there are clear benefits as illustrated by improvements in local glucose
      disposal. Training of higher intensity or duration may be required in order to
      elicit a response similar to controls.

PMID- 20146754
TI  - Successful percutaneous mechanical thrombectomy in a haemodynamically unstable
      patient with massive pulmonary embolism.
AB  - Massive pulmonary embolism with haemodynamic instability has a high mortality.
      Traditionally these patients are treated with i.v. thrombolytic therapy. When
      this therapeutic approach is contraindicated, surgical embolectomy and most
      recently, percutaneous mechanical interventions are alternative treatment
      options. This case report presents a 73-year-old female with a residual
      hemiparesis secondary to a meningioma resection 45 days previously, who presented
      with progressive shortness of breath, accompanied by oppressive chest pain,
      hypotension, tachycardia and severe hypoxaemia. CT pulmonary angiogram confirmed
      a massive pulmonary embolism extending into the lobar branches bilaterally. The
      patient was treated with percutaneous mechanical thrombectomy with excellent
      haemodynamic and clinical outcomes.

PMID- 20146755
TI  - Aerobic biodegradation of the chloroethenes: pathways, enzymes, ecology, and
      evolution.
AB  - Extensive use and inadequate disposal of chloroethenes have led to prevalent
      groundwater contamination worldwide. The occurrence of the lesser chlorinated
      ethenes [i.e. vinyl chloride (VC) and cis-1,2-dichloroethene (cDCE)] in
      groundwater is primarily a consequence of incomplete anaerobic reductive
      dechlorination of the more highly chlorinated ethenes (tetrachloroethene and
      trichloroethene). VC and cDCE are toxic and VC is a known human carcinogen.
      Therefore, their presence in groundwater is undesirable. In situ cleanup of VC-
      and cDCE-contaminated groundwater via oxidation by aerobic microorganisms is an
      attractive and potentially cost-effective alternative to physical and chemical
      approaches. Of particular interest are aerobic bacteria that use VC or cDCE as
      growth substrates (known as the VC- and cDCE-assimilating bacteria). Bacteria
      that grow on VC are readily isolated from contaminated and uncontaminated
      environments, suggesting that they are widespread and influential in aerobic
      natural attenuation of VC. In contrast, only one cDCE-assimilating strain has
      been isolated, suggesting that their environmental occurrence is rare. In this
      review, we will summarize the current knowledge of the physiology, biodegradation
      pathways, genetics, ecology, and evolution of VC- and cDCE-assimilating bacteria.
      Techniques (e.g. PCR, proteomics, and compound-specific isotope analysis) that
      aim to determine the presence, numbers, and activity of these bacteria in the
      environment will also be discussed.

PMID- 20146756
TI  - Borderline intellectual functioning in children and adolescents - insufficiently
      recognized difficulties.
AB  - AIM: To draw attention to groups of children and adolescents with borderline
      intellectual functioning, especially with respect to their school-situation.
      METHODS: In one study, population-based, children with borderline intellectual
      functioning at age 10 years were followed until they finished compulsory school
      when their final certificates could be analysed. In a second study parents of 20
      individuals in the upper secondary school for pupils with mild mental retardation
      were interviewed according to the Vineland adaptive scales and school health
      records were reviewed. In a third study pupils attending an individual programme
      in upper secondary school were assessed and we report one representative case.
      RESULTS: (1) Pupils with borderline intellectual functioning, assessed in grade
      4, received significantly lower grades when finishing the compulsory school. (2)
      In the group of pupils in the upper secondary school for the mildly mentally
      retarded, compiled data indicated that a considerable number did not fulfil the
      combined IQ and adaptive criteria for mild mental retardation. (3) The subtle
      nature of borderline intellectual functioning may delay appropriate measures at
      school, which our case illustrates. CONCLUSION: Borderline intellectual
      functioning seldom attracts attention. Our studies indicate that school and also
      society at large must be prepared to adapt educational and working conditions for
      the large minority of individuals with borderline intellectual functioning.

PMID- 20146757
TI  - Ecological Economics reviews: an introduction to the inaugural volume.

PMID- 20146758
TI  - The science of ecological economics: a content analysis of Ecological Economics,
      1989-2004.
AB  - The Ecological Economics journal is a primary source for inquiry on ecological
      economics and sustainability. To explore the scholarly pursuit of ecological
      economics, we conducted a content analysis of 200 randomly sampled research,
      survey, and methodological articles published in Ecological Economics during the
      15-year period of 1989-2004. Results of the analysis were used to investigate
      facets of transdisciplinarity within the journal. A robust qualitative approach
      was used to gather and examine data to identify themes representing substantive
      content found within the span of sampled journal papers. The extent to which each
      theme was represented was counted as well as additional data, such as author
      discipline, year published, etc. Four main categories were revealed: (1)
      foundations (self-reflexive themes stemming from direct discussions about
      ecological economics); (2) human systems, represented by the themes of values,
      social indicators of well-being, intergenerational distribution, and equity; (3)
      biophysical systems, including themes, such as carrying capacity and scarcity,
      energy, and resource use, relating directly to the biophysical aspects of
      systems; and (4) policy and management encompassing themes of development,
      growth, trade, accounting, and valuation, as well as institutional structures and
      management. The results provide empirical evidence for discussing the future
      direction of ecological economic efforts.

PMID- 20146759
TI  - Connecting thermodynamics and economics: well-lit roads and burned bridges.
AB  - Almost 40 years have passed since Georgescu-Roegen's seminal work, The Entropy
      Law and the Economic Process. During this time there has been much debate on the
      relevance of thermodynamics to economics, and many attempts to build bridges
      between the two. There has also been much confusion as to what the laws of
      thermodynamics actually say. This article clearly explains heat, work, and the
      thermodynamic laws, the meaning of entropy, and the importance of kinetics as a
      barrier to thermodynamically favorable processes. The two most important
      misunderstandings in the literature, namely entropy as disorder, and entropy as a
      measure of information, are highlighted. Reviewing the literature shows that
      thermodynamics is most relevant for building a descriptive model, or preanalytic
      vision of economics, because it implies physical constraints on production and
      consumption. Similarly, it suggests that there may be serious flaws with
      neoclassical economic models, and in particular the primacy of sustained growth.
      However, thermodynamics does not seem to aid mathematical modeling in economics,
      nor does it provide normative insights. As an aid to energy policy,
      thermodynamics is useful for assessing the feasibility of technology options-
      those that have the potential to meet our goals, and should be counted as
      options, and those that should not. But it does not provide a prescription
      outside of this technical realm. Factors, such as environmental impact, cost, and
      social acceptability, will ultimately determine which technically feasible
      options are most desirable.

PMID- 20146760
TI  - The role of input-output analysis of energy and ecologic systems. In the early
      development of ecological economics--a personal perspective.
AB  - A summary is provided of the early history of research on the flow of
      nonrenewable energy resources through the economy and of the flow of renewable
      energy resources through a natural ecosystem. The techniques are similar, and
      many specific applications are provided. A combined economic and ecological
      technique is also defined. The early history and people of the International
      Society Ecological Economic are cited.

PMID- 20146761
TI  - Agent-based modeling in ecological economics.
AB  - Interconnected social and environmental systems are the domain of ecological
      economics, and models can be used to explore feedbacks and adaptations inherent
      in these systems. Agent-based modeling (ABM) represents autonomous entities, each
      with dynamic behavior and heterogeneous characteristics. Agents interact with
      each other and their environment, resulting in emergent outcomes at the
      macroscale that can be used to quantitatively analyze complex systems. ABM is
      contributing to research questions in ecological economics in the areas of
      natural resource management and land-use change, urban systems modeling, market
      dynamics, changes in consumer attitudes, innovation, and diffusion of technology
      and management practices, commons dilemmas and self-governance, and psychological
      aspects to human decision making and behavior change. Frontiers for ABM research
      in ecological economics involve advancing the empirical calibration and
      validation of models through mixed methods, including surveys, interviews,
      participatory modeling, and, notably, experimental economics to test specific
      decision-making hypotheses. Linking ABM with other modeling techniques at the
      level of emergent properties will further advance efforts to understand dynamics
      of social-environmental systems.

PMID- 20146762
TI  - Valuing ecosystem services: theory, practice, and the need for a
      transdisciplinary synthesis.
AB  - The concept of ecosystem services has shifted our paradigm of how nature matters
      to human societies. Instead of viewing the preservation of nature as something
      for which we have to sacrifice our well-being, we now perceive the environment as
      natural capital, one of society's important assets. But ecosystem services are
      becoming increasingly scarce. In order to stop this trend, the challenge is to
      provoke society to acknowledge the value of natural capital. Ecosystem services
      valuation (ESV) is the method to tackle such a challenge. ESV is the process of
      assessing the contributions of ecosystem services to sustainable scale, fair
      distribution, and efficient allocation. It is a tool that (1) provides for
      comparisons of natural capital to physical and human capital in regard to their
      contributions to human welfare; (2) monitors the quantity and quality of natural
      capital over time with respect to its contribution to human welfare; and (3)
      provides for evaluation of projects that will affect natural capital stocks. This
      review covers: (1) what has been done in ESV research in the last 50 years; (2)
      how it has been used in ecosystem management; and (3) prospects for the future.
      Our survey of the literature has shown that over time, there has been movement
      toward a more transdisciplinary approach to ESV research which is more consistent
      with the nature of the problems being addressed. On the other hand, the
      contribution of ESV to ecosystem management has not been as significant as hoped
      nor as clearly defined. Conclusions drawn from the review are as follows: first,
      ESV researchers will have to transcend disciplinary boundaries and synthesize
      tools, skills, and methodologies from various disciplines; second, ESV research
      has to become more problem-driven rather than tool-driven because ultimately the
      success of ESV will be judged on how well it facilitates real-world decision
      making and the conservation of natural capital.

PMID- 20146763
TI  - Ecosystem valuation: a sequential decision support system and quality assessment
      issues.
AB  - Understanding the economic value of nature and the services it provides to
      humanity has become increasingly important for local, national, and global policy
      and decision making. It has become obvious that quantifying and integrating these
      services into decision making will be crucial for sustainable development.
      Problems arise in that it is difficult to obtain meaningful values for the goods
      and services that ecosystems provide and for which there is no formal market. A
      wide range of ecosystem services fall into this category. Additional problems
      arise when economic methods are applied inappropriately and when the importance
      of ecosystem maintenance for human welfare is underestimated. In this article we
      identify a place for monetary valuation within the pluralistic approach supported
      by ecological economics and assess progress to date in the application of
      environmental valuation to ecosystem service provision. We first review
      definitions of ecosystem services in order to make an operational link to
      valuation methods. We then discuss the spatially explicit nature of ecosystem
      services provision and benefits capture. We highlight the importance of valuing
      marginal changes and the role for macroscale valuation, nonlinearities in service
      benefits, and the significance of nonconvexities (threshold effects). We also
      review guidance on valuation studies quality assurance, and discuss the problems
      inherent in the methodology as exposed by the findings of behavioral economics,
      as well as with benefits transfer--the most common way valuation studies are
      applied in the policy process. We argue for a sequential decision support system
      that can lead to a more integrated and rigorous approach to environmental
      valuation and biophysical measurement of ecosystem services. This system itself
      then needs to be encompassed within a more comprehensive multicriteria assessment
      dialogue and process.

PMID- 20146764
TI  - Year in review--EROI or energy return on (energy) invested.
AB  - There have been five foremost empirical efforts regarding energy return on
      investment (EROI) analysis over the past few years, including the topics of: (1)
      whether corn ethanol is a net energy yielder; (2) a summary of the state of EROI
      for most major fuel types; (3) alternative applications of EROI, such as energy
      return on water invested (EROWI); (4) the relation between EROI and the economy;
      and (5) an attempt to calculate the minimum EROI for a sustainable society. This
      paper offers a review of these five main areas of interest and provides a history
      of the development of EROI as well as a review of some of the various definitions
      of EROI and how they apply to EROI analyses. The paper concludes by listing
      numerous areas of improvement that are needed within EROI research.

PMID- 20146765
TI  - Biofuels and sustainability.
AB  - Interest in liquid biofuels production and use has increased worldwide as part of
      government policies to address the growing scarcity and riskiness of petroleum
      use, and, at least in theory, to help mitigate adverse global climate change. The
      existing biofuels markets are dominated by U.S. ethanol production based on
      cornstarch, Brazilian ethanol production based on sugarcane, and European
      biodiesel production based on rapeseed oil. Other promising efforts have included
      programs to shift toward the production and use of biofuels based on residues and
      waste materials from the agricultural and forestry sectors, and perennial
      grasses, such as switchgrass and miscanthus--so-called cellulosic ethanol. This
      article reviews these efforts and the recent literature in the context of
      ecological economics and sustainability science. Several common dimensions for
      sustainable biofuels are discussed: scale (resource assessment, land
      availability, and land use practices); efficiency (economic and energy); equity
      (geographic distribution of resources and the "food versus fuel" debate); socio
      economic issues; and environmental effects and emissions. Recent proposals have
      been made for the development of sustainable biofuels criteria, culminating in
      standards released in Sweden in 2008 and a draft report from the international
      Roundtable on Sustainable Biofuels. These criteria hold promise for accelerating
      a shift away from unsustainable biofuels based on grain, such as corn, and toward
      possible sustainable feedstock and production practices that may be able to meet
      a variety of social, economic, and environmental sustainability criteria.

PMID- 20146766
TI  - Reassessing the forest impacts of protection: the challenge of nonrandom location
      and a corrective method.
AB  - Protected areas are leading tools in efforts to slow global species loss and
      appear also to have a role in climate change policy. Understanding their impacts
      on deforestation informs environmental policies. We review several approaches to
      evaluating protection's impact on deforestation, given three hurdles to empirical
      evaluation, and note that "matching" techniques from economic impact evaluation
      address those hurdles. The central hurdle derives from the fact that protected
      areas are distributed nonrandomly across landscapes. Nonrandom location can be
      intentional, and for good reasons, including biological and political ones. Yet
      even so, when protected areas are biased in their locations toward less
      threatened areas, many methods for impact evaluation will overestimate
      protection's effect. The use of matching techniques allows one to control for
      known landscape biases when inferring the impact of protection. Applications of
      matching have revealed considerably lower impact estimates of forest protection
      than produced by other methods. A reduction in the estimated impact from existing
      parks does not suggest, however, that protection is unable to lower clearing.
      Rather, it indicates the importance of variation across locations in how much
      impact protection could possibly have on rates of deforestation. Matching, then,
      bundles improved estimates of the average impact of protection with guidance on
      where new parks' impacts will be highest. While many factors will determine where
      new protected areas will be sited in the future, we claim that the variation
      across space in protection's impact on deforestation rates should inform site
      choice.

PMID- 20146767
TI  - Economic valuation of climate change adaptation in developing countries.
AB  - This paper reviews the literature on the economics of climate change adaptation
      in developing countries, and identifies three key points for consideration in
      future studies. One key point is that all development policy should be formulated
      using forecasts from climate science as a baseline. When this is not done, there
      is risk that a false status quo without climate change is seen as an implicit
      baseline. Another key point is that authors must be clearer about their
      behavioral assumptions: Many studies either (problematically) assume profit
      maximization on the side of farm households, or do not specify behavioral
      assumptions at all. A third important point is that the allocation of rights is
      crucial for the results; if households have a right to maintain their current
      livelihoods, the costs of climate change in developing countries are considerably
      greater than traditional willingness-to-pay studies would indicate. Thus, costs
      and benefits of climate change adaptation cannot be analyzed using economic
      aspects only; climate science, behavioral science, and legal and moral aspects
      have crucial implications for the outcome of the analysis.

PMID- 20146768
TI  - Commoditization and oppression: a systems approach to understanding the economic
      dynamics of modes of oppression.
AB  - Commoditization is a generalized Darwinian selection pressure in economic
      evolution driven by profit- and efficiency-seeking in the investment of key
      resources. By winnowing noncommodity opportunities to satisfy human needs,
      commoditization distorts development in ways that intensify negative social
      outcomes experienced by oppressed groups and undermines the possibility for
      sustainable development. When market logic dominates the investment of financial
      capital, energy, raw materials, human attention, labor, and creativity, market
      goods with traits associated with commodities are fully developed while nonmarket
      goods lacking those traits are systematically underdeveloped. Analysis of the
      traits of commodities explains the unsustainable development or maldevelopment
      that disproportionately affects those who are dependent on or who highly value
      important nonmarket relationships. Oppression theory is addressed with specific
      examples. A generalized form of oppression is theorized that systematically
      stunts the imagination and creativity required to meet contemporary environmental
      crises.

PMID- 20146769
TI  - Democratizing economics: pluralism as a path toward sustainability.
AB  - Climate scientists point to a number of unsustainable trends concerning the
      environment and natural resources. There is also ongoing concern about poverty
      reduction, labor rights, and other social aspects of sustainable development.
      Growing numbers argue that change is required, but still at issue is the extent
      of change and how to facilitate it. In this paper, the focus is on the dominant
      interpretive schema of influential actors with respect to ideas about science in
      society, paradigms in economics, and ideological orientations. The authors argue
      that the monopolistic position of neoclassical economics at university
      departments of economics in different parts of the world, and the spread of its
      associated technocratic logic within broader policy arenas, should be abandoned
      in favor of a more ideologically open attitude that facilitates discussion and
      debate within academia, public policy, and in civil society more generally. In a
      sense, economics requires "democratization" with implications for approaches to
      sustainability monitoring, accounting, and the assessment of projects and
      policies. The paper provides suggestions for developing sustainability assessment
      technologies and practices that take pluralism seriously.

PMID- 20146770
TI  - Public sector administration of ecological economics systems using mediated
      modeling.
AB  - In today's climate of government outsourcing and multiple stakeholder involvement
      in public sector management and service delivery, it is more important than ever
      to rethink and redesign the structure of how policy decisions are made,
      implemented, monitored, and adapted to new realities. The traditional command-and
      control approach is now less effective because an increasing amount of
      responsibility to deliver public goods and services falls on networks of
      nongovernment agencies. Even though public administrators are seeking new
      decision-making models in an increasingly more complex environment, the public
      sector currently only sparsely utilizes Mediated Modeling (MM). There is growing
      evidence, however, that by employing MM and similar tools, public interest
      networks can be better equipped to deal with their long-term viability while
      maintaining the short-term needs of their clients. However, it may require a
      shift in organizational culture within and between organizations to achieve the
      desired results. This paper explores the successes and barriers to implementing
      MM and similar tools in the public sector and offers insights into utilizing them
      through a review of case studies and interdisciplinary literature. We aim to
      raise a broader interest in MM and similar tools among public sector
      administrators at various administrative levels. We focus primarily, but not
      exclusively, on those cases operating at the interface of ecology and socio
      economic systems.

PMID- 20146771
TI  - Pro-environmental behavior: rational choice meets moral motivation.
AB  - The determinants of individual behaviors that provide shared environmental
      benefits are a longstanding theme in social science research. Alternative
      behavioral models yield markedly different predictions and policy
      recommendations. This paper reviews and compares the literatures from two
      disciplines that appear to be moving toward a degree of convergence. In social
      psychology, moral theories of pro-environmental behavior have focused on the
      influence of personal moral norms while recognizing that external factors, such
      as costs and incentives, ultimately limit the strength of the norm-behavior
      relationship. Rational choice models, such as the theory of planned behavior in
      social psychology and the theories of voluntary provision of public goods in
      economics, have sought to incorporate the effects of personal norms and to
      measure their importance in explaining behaviors, such as recycling and the
      demand for green products. This paper explores the relationship between these
      approaches and their implications for the theory and practice of ecological
      economics.

PMID- 20146773
TI  - Ecological economics and economic growth.
AB  - Boulding's 1966 paper on the economics of spaceship Earth established the
      framework for ecological economics and an understanding of economic growth. In
      ecological economics, economies are conceptualized as open subsystems of the
      closed biosphere and are subject to biophysical laws and constraints. Economic
      growth measured as an increase in real gross domestic product (GDP) has generally
      been associated with increases in the use of energy and materials and the
      generation of wastes. Scale, composition, and technology are the proximate
      determinants of environmental impacts. They are often reduced to two: scale (GDP)
      and intensity (impact per unit GDP). New work described in this paper defines
      "green" growth as intensity that declines faster than scale increases. Similarly,
      "brown" growth occurs when intensity declines more slowly than increases in
      scale, and "black" growth happens when both scale and intensity increase. These
      concepts are then related to the environmental Kuznets curve, which can be
      understood as a transition from brown to green growth. Ecological economics
      provides a macroperspective on economic growth. It offers broad policy
      principles, and it challenges the primacy of economic growth as a policy
      objective, but many important questions remain.

PMID- 20146772
TI  - The road to sustainability must bridge three great divides.
AB  - The world's large and rapidly growing human population is exhausting Earth's
      natural capital at ever-faster rates, and yet appears mostly oblivious to the
      fact that these resources are limited. This is dangerous for our well-being and
      perhaps for our survival, as documented by numerous studies over many years. Why
      are we not moving instead toward sustainable levels of use? We argue here that
      this disconnection between our knowledge and our actions is largely caused by
      three "great divides": an ideological divide between economists and ecologists;
      an economic development divide between the rich and the poor; and an information
      divide, which obstructs communications between scientists, public opinion, and
      policy makers. These divides prevent our economies from responding effectively to
      urgent signals of environmental and ecological stress. The restoration of natural
      capital (RNC) can be an important strategy in bridging all of these divides. RNC
      projects and programs make explicit the multiple and mutually reinforcing
      linkages between environmental and economic well-being, while opening up a
      promising policy road in the search for a sustainable and desirable future for
      global society. The bridge-building capacity of RNC derives from its double
      focus: on the ecological restoration of degraded, overexploited natural
      ecosystems, and on the full socio-economic and ecological interface between
      people and their environments.

PMID- 20146774
TI  - The pursuit of optimal distinctiveness and consumer preferences.
AB  - This article investigates the effect of optimal distinctiveness on consumer
      product consumption. The authors argue that consumers acquire and display
      material possessions to restore their optimal levels of distinctiveness. Results
      showed that placing consumers in a state of low distinctiveness increased desire
      to acquire distinctive products, whereas perceptions of high distinctiveness
      reduced desire to acquire such products. Consumers' desire for distinctiveness
      related products held true for various consumer choices, including willingness to
      pay more for limited-edition products and preference for unpopular gifts. This
      finding has implications for understanding consumer choice in expressing
      identity.

PMID- 20146775
TI  - Gender differences in ECG parameters and their clinical implications.

PMID- 20146777
TI  - Behavior of the electrocardiographic T peak to end interval in childhood.
AB  - BACKGROUND: The T-wave peak to T-wave end (TpTe) interval reflects spatial and
      transmural dispersion in repolarization and serves as an arrhythmogenic index.
      Normal TpTe interval data in children are lacking. We evaluated the effects of
      age, gender, heart rate, leads (II and V(5)) on TpTe and T-wave voltage. METHODS:
      Four hundred healthy children (age 4 days to 16.7 years) were enrolled. From a
      resting 12-lead digital ECG, TpTe, RR, QT, JT intervals, and T amplitude were
      measured (leads II and V(5)). Bazett and Fridericia formulas were applied to TpTe
      for heart rate correction and TpTe/QT and TpTe/JT were calculated. Descriptive
      and analytical statistics were applied, significance level set at P < or = 0.05.
      RESULTS: TpTe in leads II and V(5) correlate well. Contrary to adults, no gender
      differences in TpTe were observed in childhood. TpTe lengthens with increasing
      age, and is inversely related to heart rate. TpTe 98th percentile is 85 msec in
      first 5 years, increasing to 92 msec in adolescence. TpTe Fridericia is a good
      correction formula in childhood; TpTe Bazett overcorrects in the younger age.
      TpTe/QT and TpTe/JT are longer in younger subjects due to greater QT shortening
      than the TpTe interval at higher heart rates. CONCLUSIONS: In children, TpTe in
      lead II and V(5) correlate well. The TpTe interval lengthens with advancing age
      as heart rate diminishes. TpTe Fridericia is a good correction formula in
      children. Younger subjects have higher TpTe/QT and TpTe/JT indices compared to
      older children. T-wave voltage increases with age, tallest in the 5-10-year-age
      group particularly in V(5).

PMID- 20146776
TI  - Circadian and gender effects on repolarization in healthy adults: a study using
      harmonic regression analysis.
AB  - BACKGROUND: Sudden cardiac death and myocardial infarction have a circadian
      variation with a peak incidence in the early morning hours. Increased dispersion
      of repolarization facilitates the development of conduction delay necessary to
      induce sustained arrhythmia. Both QT-dispersion and T-wave peak to T-wave end
      (TpTe) have been proposed as markers of dispersion of myocardial repolarization.
      METHODS: Forty healthy adults (20 women), age 35-67 years old, with normal EKGs,
      echocardiograms, stress tests, and tilt-table tests were analyzed during a 27
      hour hospital stay. EKGs were done at eight different time points. QT-intervals,
      QT-dispersion, and TpTe were measured at each time point. Harmonic regression was
      used to model circadian periodicity, P < 0.05 was considered significant.
      RESULTS: The composite QT-interval was longer in women than in men (416 + or - 17
      msec vs 411 + or - 20 msec, respectively, P = 0.006). The QT-dispersion among all
      leads was greater in men than women (37 + or - 13 msec vs 30 + or - 11 msec,
      respectively, P < 0.0001); a similar difference was found in the precordial
      leads. Harmonic regression showed that QT-dispersion had a significant circadian
      variation, primarily in men. In men, the maximum QT-dispersion occurred at 6 AM
      (45 + or - 15 msec). TpTe also had a significant circadian variation that was not
      affected by gender in the majority of leads. CONCLUSIONS: A circadian variation
      exists in the dispersion of myocardial repolarization, as measured by both TpTe
      and QT-dispersion. Men and women have a different circadian variation pattern.
      Further studies regarding the mechanisms and clinical implications are needed.

PMID- 20146778
TI  - Prevalence of interatrial block in healthy school-aged children: definition by P
      wave duration or morphological analysis.
AB  - BACKGROUND: P waves > or = 110 ms in adults and > or = 90 ms in children are
      considered abnormal, signifying interatrial block, particularly in the first
      case. METHODS: To evaluate the prevalence of interatrial block in healthy school
      aged children, we obtained 12-lead digital ECGs (Cardioperfect 1.1, CardioControl
      NV, Delft, The Netherlands) of 664 healthy children (349 males/315 females, age
      range 6-14 years old). P-wave analysis indices [mean, maximum and minimum (in the
      12 leads) P-wave duration, P-wave dispersion, P-wave morphology in the derived
      orthogonal (X, Y, Z) leads, as well the amplitude of the maximum spatial P-wave
      vector] were calculated in all study participants. RESULTS: P-wave descriptor
      values were: mean P-wave duration 84.9 + or - 9.5 ms, maximum P-wave duration
      99.0 + or - 9.8 ms, P dispersion 32.2 + or - 12.5 ms, spatial P amplitude 182.7 +
      or - 69.0 microV. P-wave morphology distribution in the orthogonal leads were:
      Type I 478 (72.0%), Type II 178 (26.8%), Type III 1 (0.2%), indeterminate 7 (1%).
      Maximum P-wave duration was positively correlated to age (P < 0.001) and did not
      differ between sexes (P = 0.339). Using the 90-ms value as cutoff for P-wave
      duration, 502 (75.6%) children would be classified as having maximum P-wave
      duration above reference range. The 95th and the 99th percentiles were in the
      overall population 117 ms and 125 ms, respectively. P-wave morphology type was
      not in any way correlated to P-wave duration (P = 0.715). CONCLUSIONS: Abnormal P
      wave morphology signifying the presence of interatrial block is very rare in a
      healthy pediatric population, while widened P waves are quite common, although
      currently classified as abnormal.

PMID- 20146779
TI  - The time course of new T-wave ECG descriptors following single- and double-dose
      administration of sotalol in healthy subjects.
AB  - INTRODUCTION: The aim of the study was to assess the time course effect of IKr
      blockade on ECG biomarkers of ventricular repolarization and to evaluate the
      accuracy of a fully automatic approach for QT duration evaluation. METHODS:
      Twelve-lead digital ECG Holter was recorded in 38 healthy subjects (27 males,
      mean age = 27.4 + or - 8.0 years) on baseline conditions (day 0) and after
      administration of 160 mg (day 1) and 320 mg (day 2) of d-l sotalol. For each 24
      hour period and each subject, ECGs were extracted every 10 minutes during the 4
      hour period following drug dosage. Ventricular repolarization was characterized
      using three biomarker categories: conventional ECG time intervals, principal
      component analysis (PCA) analysis on the T wave, and fully automatic biomarkers
      computed from a mathematical model of the T wave. RESULTS: QT interval was
      significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg
      and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular
      repolarization parameters sotalol-induced changes were delayed (>3 hours). After
      sotalol dosing, the early phase of the T wave changed earlier than the late phase
      prolongation. Globally, the modeled surrogate QT paralleled manual QT changes.
      The duration of manual QT and automatic surrogate QT were strongly correlated
      (R(2) = 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary
      systematic bias (bias = 26.5 ms + or - 1.96*SD = 16 ms). CONCLUSIONS: Changes in
      different ECG biomarkers of ventricular repolarization display different kinetics
      after administration of a potent potassium channel blocker. These differences
      need to be taken into account when designing ventricular repolarization ECG
      studies.

PMID- 20146780
TI  - Optimization of repolarization during biventricular pacing: a new target in
      patients with biventricular devices?
AB  - BACKGROUND: Evaluation of repolarization during sequentional biventricular
      pacing. METHODS: Patients with biventricular devices, and left ventricular leads
      placed to the basal part of lateral left ventricular wall were enrolled. QRS,
      QTc, JTc, and corrected Tpeak-Tend intervals were compared during sequentional
      biventricular, left ventricular, and right ventricular pacing. RESULTS: Five
      patients with nonischemic and five with ischemic cardiomyopathy due to anterior
      myocardial infarction were enrolled. No correlation was observed between values
      of repolarization among patients. The optimal values of repolarization were
      significantly different from values of echocardiographically guided hemodynamic
      optimization. Two patients with biventricular pacing-induced ventricular
      fibrillation were successfully treated by reprogramming of V-V delay according to
      interventricular delay resulting in shorter Tpeak-Tend interval, although delayed
      effect of amiodarone in one of these patients cannot be ruled out. CONCLUSIONS:
      Patients with biventricular devices may be prone to development of ventricular
      arrhythmias depending on programmed V-V interval. We suggest that optimization of
      repolarization may be performed in patients with biventricular pacemakers in the
      absence of backup ICD and those with frequent episodes of ventricular
      tachyarrhythmias, although this finding deserves further study.

PMID- 20146781
TI  - Influence of the maximum heart rate attained during exercise testing on
      subsequent heart rate recovery.
AB  - BACKGROUND: Abnormal heart rate recovery (HRR) following exercise testing has
      been shown to be a predictor for adverse cardiovascular events. The actual
      maximum heart rate (MHR) attained during the exercise test does not however have
      a distinct significance in traditional HRR assessment. The objective of this
      study was to investigate the role of MHR in HRR. METHODS: This prospective study
      consisted of 164 patients (62% male, mean age 53.7 + or - 11.7 years) who were
      referred for a symptom-limited standard Bruce Protocol treadmill exercise test,
      based on clinical indications. The patients were seated immediately at test
      completion and the heart rate (HR) recorded at one and two minutes postexercise.
      A normal HRR was defined as a HR drop of 18 beats per minute or more at the end
      of the first minute of recovery. The HRR profile of patients who reached > or =
      85% of their maximum predicted heart rate (MPHR) during peak exercise were then
      compared to HRR profile of those who could not. RESULTS: One hundred twelve
      patients (Group A) achieved a MHR > or = 85% of MPHR during peak exercise whereas
      52 patients (Group B) did not. Chi-square analysis showed a higher incidence of
      normal HRR in Group A compared to Group B (p = 0.029). Analysis of variance with
      repeated measures showed that group A had a greater HRR at the first minute
      F(1,162)= 6.98, p = <0.01) but not the second minute (F(1,162)=1.83, p = .18)
      postexercise. CONCLUSION: There is a relation between the peak heart rate
      attained during exercise and the subsequent HRR. A low peak heart rate increases
      the likelihood of a less than normal HRR. Assessment of the entire heart-rate
      response seems warranted for more thorough risk-stratification.

PMID- 20146782
TI  - Autonomic nervous system modulation before the onset of sustained
      atrioventricular nodal reentry tachycardia.
AB  - INTRODUCTION: Our study was designed to analyze dynamic changes in autonomic tone
      before the onset of typical sustained atrioventricular nodal reentry tachycardia
      (AVNRT) in a large group of patients without structural heart disease. MATERIALS
      AND METHODS: Twenty-four-hour Holter tapes from 42 consecutive patients (27 men
      and 15 women; aged 30 + or - 21 years) with several episodes of sustained typical
      AVNRT were analyzed. The diagnosis was validated by transesophageal
      electrophysiological study. The time-domain calculated parameters were SDNN,
      SDANN, rMSSD, pNN50; the frequency-domain parameters were low-frequency power
      (LF, 0.04-0.15 Hz), high-frequency power (HF, 0.15-0.40 Hz), very low-frequency
      power (VLF, 0.008 to 0.04 Hz) and LF/HF. The mean values in the hour before the
      onset of sustained AVNRT were compared with the mean values of 2 hours before and
      1 hour after the onset of sustained AVNRT. RESULTS: The mean SDNN, rMSSD, pNN50,
      HF were significantly decreased during the hour preceding the onset of AVNRT,
      when compared to the mean values observed during the time periods selected.
      Instead, the LF values and LF/HF were increased before the onset of sustained
      AVNRT. No significant change in the VLF and atrial ectopic beats were observed.
      CONCLUSION: This study suggests that sustained typical AVNRT episodes are
      preceded by increase in adrenergic drive.

PMID- 20146783
TI  - Rest premature ventricular contractions on routine ECG and prognosis in heart
      failure patients.
AB  - BACKGROUND: Premature ventricular contractions (PVC) at rest are frequently seen
      in heart failure (HF) patients but conflicting data exist regarding their
      importance for cardiovascular (CV) mortality. This study aims to evaluate the
      prognostic value of rest PVCs on an electrocardiogram (ECG) in patients with a
      history of clinical HF. METHODS AND RESULTS: We considered 352 patients (64 + or 
      11 years; 7 females) with a history of clinical HF undergoing treadmill testing
      for clinical reasons at the Veterans Affairs Palo Alto Health Care System
      (VAPAHCS) (1987-2007). Patients with rest PVCs were defined as having > or = 1
      PVC on the ECG prior to testing (n = 29; 8%). During a median follow-up period of
      6.2 years, there were 178 deaths of which 76 (42.6%) were due to CV causes. At
      baseline, compared to patients without rest PVCs, those with rest PVCs had a
      lower ejection fraction (EF) (30% vs 45%) and the prevalence of EF < or = 35% was
      higher (75% vs 41%). They were more likely to have smoked (76% vs 55%).The all
      cause and CV mortality rates were significantly higher in the rest PVCs group
      (72% vs 49%, P = 0.01 and 45% vs 20%, P = 0.002; respectively). After adjusting
      for age, beta-blocker use, rest ECG findings, resting heart rate (HR), EF,
      maximal systolic blood pressure, peak HR, and exercise capacity, rest PVC was
      associated with a 5.5-fold increased risk of CV mortality (P = 0.004).
      Considering the presence of PVCs during exercise and/or recovery did not affect
      our results. CONCLUSION: The presence of PVC on an ECG is a powerful predictor of
      CV mortality even after adjusting for confounding factors.

PMID- 20146784
TI  - Abnormal P-wave morphology is a predictor of atrial fibrillation development and
      cardiac death in MADIT II patients.
AB  - BACKGROUND: Several ECG-based approaches have been shown to add value when risk
      stratifying patients with congestive heart failure, but little attention has been
      paid to the prognostic value of abnormal atrial depolarization in this context.
      The aim of this study was to noninvasively analyze the atrial depolarization
      phase to identify markers associated with increased risk of mortality,
      deterioration of heart failure, and development of atrial fibrillation (AF) in a
      high-risk population with advanced congestive heart failure and a history of
      acute myocardial infarction. METHODS: Patients included in the Multicenter
      Automatic Defibrillator Implantation Trial II (MADIT II) with sinus rhythm at
      baseline were studied (n = 802). Unfiltered and band-pass filtered signal
      averaged P waves were analyzed to determine orthogonal P-wave morphology
      (prespecified types 1, 2, and 3/atypical), P-wave duration, and RMS20. The
      association between P-wave parameters and data on the clinical course and cardiac
      events during a mean follow-up of 20 months was analyzed. RESULTS: P-wave
      duration was 139 + or - 23 ms and the RMS20 was 1.9 + or - 1.1 microV. None of
      these parameters was significantly associated with poor cardiac outcome or AF
      development. After adjustment for clinical covariates, abnormal P-wave morphology
      was found to be independently predictive of nonsudden cardiac death (HR 2.66; 95%
      CI 1.41-5.04, P = 0.0027) and AF development (HR 1.75; 95% CI 1.10-2.79, P =
      0.019). CONCLUSION: Abnormalities in P-wave morphology recorded from orthogonal
      leads in surface ECG are independently predictive of increased risk of nonsudden
      cardiac death and AF development in MADIT II patients.

PMID- 20146785
TI  - Long QT syndrome in African-Americans.
AB  - BACKGROUND: We evaluated the risk factors and clinical course of Long QT syndrome
      (LQTS) in African-American patients. METHODS: The study involved 41 African
      Americans and 3456 Caucasians with a QTc > or = 450 ms from the U.S. portion of
      the International LQTS Registry. Data included information about the medical
      history and clinical course of the LQTS patients with end points relating to the
      occurrence of syncope, aborted cardiac arrest, or LQTS-related sudden cardiac
      death from birth through age 40 years. The statistical analyses involved Kaplan
      Meier time to event graphs and Cox regression models for multivariable risk
      factor evaluation. RESULTS: The QTc was 29 ms longer in African-Americans than
      Caucasians. Multivarite Cox analyses with adjustment for decade of birth revealed
      that the cardiac event rate was similar in African-Americans and Caucasians with
      LQTS and that beta-blockers were equally effective in reducing cardiac events in
      the two racial groups. CONCLUSIONS: The clinical course of LQTS in African
      Americans is similar to that of Caucasians with comparable risk factors and
      benefit from beta-blocker therapy in the two racial groups.

PMID- 20146787
TI  - The year of 2008 in electrocardiology.

PMID- 20146786
TI  - P-wave indices, distribution and quality control assessment (from the Framingham
      Heart Study).
AB  - BACKGROUND: P-wave indices of maximum P-wave duration and P-wave dispersion have
      been examined in a broad array of cardiovascular and noncardiovascular disease
      states. The P-wave indices literature has been highly heterogeneous in
      measurement methodologies, described quality control metrics, and distribution of
      values. We therefore sought to determine the reproducibility of P-wave indices in
      a community-based cohort. METHODS: P-wave indices were measured in sequential
      subjects enrolled in the Framingham Heart Study. Electrocardiograms were obtained
      at the 11th biennial visit of the Original Cohort (n = 250) and the initial visit
      of the Offspring Cohort (n = 252). We determined the mean P-wave durations,
      interlead correlations, and P-wave indices. We then chose 20 ECGs, 10 from each
      cohort, and assessed intrarater and interrater variability. RESULTS: The maximum
      P-wave duration ranged from 71 to 162 ms with mean of 112 + or - 12 ms. The
      minimum P-wave duration ranged from 35 to 103 ms with mean of 65 + or - 10 ms. P
      wave dispersion ranged from 12 to 82 ms. The mean P-wave dispersion was 48 + or -
      12 ms (40-56). The intrarater intraclass correlation coefficient (ICC) was r =
      0.80 for maximum P-wave duration and r = 0.82 for P-wave dispersion. The
      interrater ICC was 0.56 for maximum P-wave duration and 0.70 for P-wave
      dispersion. CONCLUSIONS: We demonstrated excellent intrarater reproducibility and
      fair interrater reproducibility for calculating P-wave indices. Reproducibility
      is frequently lacking in studies of P-wave indices, but is an essential component
      for the field's growth and epidemiologic contribution.

PMID- 20146788
TI  - Inferolateral ST elevation as a first sign of left anterior descending artery
      occlusion.
AB  - Combined anterior and inferior ST elevation due to occlusion of wrapped left
      anterior descending artery (LAD) is well reported in the literature. However,
      there is rare literature mentioned about inferolateral ST elevation in this
      patient group. Herein, we report a case of acute proximal wrapped LAD occlusion
      with initial electrocardiographic sign of inferolateral ST elevation. The most
      likely mechanism of this electrocardiographic finding might be related to old
      anteroseptal myocardial infarction, combination with other coronary abnormality,
      such as chronic total occlusion of left circumflex artery that caused larger
      injury current in inferolateral than anteroseptal myocardium, and made
      anteroseptal leads reveal isoelectric pattern.

PMID- 20146790
TI  - Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved
      survival with angiogenesis inhibitor or asparaginase treatment in mice with
      subcutaneous tuberous sclerosis related tumors.
AB  - BACKGROUND: Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor
      disorder characterized by the growth of hamartomas in various organs including
      the kidney, brain, skin, lungs, and heart. Rapamycin has been shown to reduce the
      size of kidney angiomyolipomas associated with TSC; however, tumor regression is
      incomplete and kidney angiomyolipomas regrow after cessation of treatment. Mouse
      models of TSC2 related tumors are useful for evaluating new approaches to drug
      therapy for TSC. METHODS: In cohorts of Tsc2+/- mice, we compared kidney
      cystadenoma severity in A/J and C57BL/6 mouse strains at both 9 and 12 months of
      age. We also investigated age related kidney tumor progression and compared three
      different rapamycin treatment schedules in cohorts of A/J Tsc2+/- mice. In
      addition, we used nude mice bearing Tsc2-/- subcutaneous tumors to evaluate the
      therapeutic utility of sunitinib, bevacizumab, vincristine, and asparaginase.
      RESULTS: TSC related kidney disease severity is 5-10 fold higher in A/J Tsc2+/-
      mice compared with C57BL/6 Tsc2+/- mice. Similar to kidney angiomyolipomas
      associated with TSC, the severity of kidney cystadenomas increases with age in
      A/J Tsc2+/- mice. When rapamycin dosing schedules were compared in A/J Tsc2+/-
      cohorts, we observed a 66% reduction in kidney tumor burden in mice treated daily
      for 4 weeks, an 82% reduction in mice treated daily for 4 weeks followed by
      weekly for 8 weeks, and an 81% reduction in mice treated weekly for 12 weeks. In
      the Tsc2-/- subcutaneous tumor mouse model, vincristine is not effective, but
      angiogenesis inhibitors (sunitinib and bevacizumab) and asparaginase are
      effective as single agents. However, these drugs are not as effective as
      rapamycin in that they increased median survival only by 24-27%, while rapamycin
      increased median survival by 173%. CONCLUSIONS: Our results indicate that the A/J
      Tsc2+/- mouse model is an improved, higher through-put mouse model for future TSC
      preclinical studies. The rapamycin dosing comparison study indicates that the
      duration of rapamycin treatment is more important than dose intensity. We also
      found that angiogenesis inhibitors and asparaginase reduce tumor growth in a TSC2
      tumor mouse model and although these drugs are not as effective as rapamycin,
      these drug classes may have some therapeutic potential in the treatment of TSC
      related tumors.

PMID- 20146791
TI  - Distinct, ecotype-specific genome and proteome signatures in the marine
      cyanobacteria Prochlorococcus.
AB  - BACKGROUND: The marine cyanobacterium Prochlorococcus marinus, having multiple
      ecotypes of distinct genotypic/phenotypic traits and being the first documented
      example of genome shrinkage in free-living organisms, offers an ideal system for
      studying niche-driven molecular micro-diversity in closely related microbes. The
      present study, through an extensive comparative analysis of various
      genomic/proteomic features of 6 high light (HL) and 6 low light (LL) adapted
      strains, makes an attempt to identify molecular determinants associated with
      their vertical niche partitioning. RESULTS: Pronounced strand-specific asymmetry
      in synonymous codon usage is observed exclusively in LL strains. Distinct
      dinucleotide abundance profiles are exhibited by 2 LL strains with larger genomes
      and G+C-content approximately 50% (group LLa), 4 LL strains having reduced
      genomes and G+C-content approximately 35-37% (group LLb), and 6 HL strains.
      Taking into account the emergence of LLa, LLb and HL strains (based on 16S rRNA
      phylogeny), a gradual increase in average aromaticity, pI values and beta- & coil
      forming propensities and a decrease in mean hydrophobicity, instability indices
      and helix-forming propensities of core proteins are observed. Greater variations
      in orthologous gene repertoire are found between LLa and LLb strains, while
      higher number of positively selected genes exist between LL and HL strains.
      CONCLUSION: Strains of different Prochlorococcus groups are characterized by
      distinct compositional, physicochemical and structural traits that are not mere
      remnants of a continuous genetic drift, but are potential outcomes of a grand
      scheme of niche-oriented stepwise diversification, that might have driven them
      chronologically towards greater stability/fidelity and invoked upon them a
      special ability to inhabit diverse oceanic environments.

PMID- 20146792
TI  - Bilateral changes of TNF-alpha and IL-10 protein in the lumbar and cervical
      dorsal root ganglia following a unilateral chronic constriction injury of the
      sciatic nerve.
AB  - BACKGROUND: There is a growing body of evidence that unilateral nerve injury
      induces bilateral response, the mechanism of which is not exactly known. Because
      cytokines act as crucial signaling molecules for response of peripheral nerves to
      injury, they may be induced to mediate the reaction in remote structures.
      METHODS: We studied levels of tumor necrosis factor alpha (TNF-alpha) and
      interleukin 10 (IL-10) proteins using ELISA in the ipsilateral and contralateral
      lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) from naive rats,
      rats operated on to create unilateral chronic constriction injury (CCI) of the
      sciatic nerve, and sham-operated rats. Withdrawal thresholds for mechanical
      allodynia and thermal hyperalgesia were measured in the ipsilateral and
      contralateral hind and forepaws. RESULTS: The ipsilateral hind paws of all rats
      operated upon for CCI displayed decreased withdrawal thresholds for mechanical
      allodynia and thermal hyperalgesia, while no significant behavioral changes were
      found in the contralateral hind paws and both forepaws. Significantly lower
      baseline levels of TNF-alpha and IL-10 protein were measured by ELISA in the
      lumbar than cervical DRG of naive rats. Bilateral elevation of TNF-alpha was
      induced in both the lumbar and cervical DRG by unilateral CCI of the sciatic
      nerve for 7 and 14 days, while the level of IL-10 protein was increased
      bilaterally in the lumbar DRG 1 and 3 days after operation. IL-10 levels declined
      bilaterally even below baseline level in both cervical and lumbar DRG 7 days from
      CCI and normalized after 14 days. In contrast to no significant changes in TNF
      alpha, level of IL-10 protein was significantly increased in the ipsilateral
      lumbar DRG after 3 days and bilaterally in the lumbar DRG after 14 days from sham
      operation. CONCLUSIONS: The results of our experiments show a bilateral elevation
      of TNF-alpha and IL-10 not only in the homonymous DRG but also in the
      heteronymous DRG unassociated with the injured nerve. This suggests that
      bilaterally increased levels of TNF-alpha and IL-10 in DRG following unilateral
      CCI are linked with general neuroinflammatory reaction of the nervous system to
      injury rather than only to development and maintenance of neuropathic pain.

PMID- 20146793
TI  - Supervised and non-supervised Nordic walking in the treatment of chronic low back
      pain: a single blind randomized clinical trial.
AB  - BACKGROUND: Active approaches including both specific and unspecific exercise are
      probably the most widely recommended treatment for patients with chronic low back
      pain but it is not known exactly which types of exercise provide the most
      benefit. Nordic Walking - power walking using ski poles - is a popular and fast
      growing type of exercise in Northern Europe that has been shown to improve
      cardiovascular metabolism. Until now, no studies have been performed to
      investigate whether Nordic Walking has beneficial effects in relation to back
      pain. METHODS: A total of 151 patients with low back and/or leg pain of greater
      than eight weeks duration were recruited from a hospital based outpatient back
      pain clinic. Patients continuing to have pain greater than three on the 11-point
      numeric rating scale after a multidisciplinary intervention were included.
      Fifteen patients were unable to complete the baseline evaluation and 136 patients
      were randomized to receive A) Nordic walking supervised by a specially trained
      instructor twice a week for eight weeks B) One-hour instruction in Nordic walking
      by a specially trained instructor followed by advice to perform Nordic walking at
      home as much as they liked for eight weeks or C) Individual oral information
      consisting of advice to remain active and about maintaining the daily function
      level that they had achieved during their stay at the backcenter. Primary outcome
      measures were pain and disability using the Low Back Pain Rating Scale, and
      functional limitation further assessed using the Patient Specific Function Scale.
      Furthermore, information on time off work, use of medication, and concurrent
      treatment for their low back pain was collected. Objective measurements of
      physical activity levels for the supervised and unsupervised Nordic walking
      groups were performed using accelerometers. Data were analyzed on an intention-to
      treat basis. RESULTS: No mean differences were found between the three groups in
      relation to any of the outcomes at baseline. For pain, disability, and patient
      specific function the supervised Nordic walking group generally faired best
      however no statistically significant differences were found. Regarding the
      secondary outcome measures, patients in the supervised group tended to use less
      pain medication, to seek less concurrent care for their back pain, at the eight
      week follow-up. There was no difference between physical activity levels for the
      supervised and unsupervised Nordic walking groups. No negative side effects were
      reported. CONCLUSION: We did not find statistically significant differences
      between eight weeks of supervised or unsupervised Nordic walking and advice to
      remain active in a group of chronic low back pain patients. Nevertheless, the
      greatest average improvement tended to favor the supervised Nordic walking group
      and - taking into account other health related benefits of Nordic walking - this
      form of exercise may potentially be of benefit to selected groups of chronic back
      pain patients. TRIAL REGISTRATION: http://www.ClinicalTrials.gov # NCT00209820.

PMID- 20146794
TI  - Study protocol: cost-effectiveness of transmural nutritional support in
      malnourished elderly patients in comparison with usual care.
AB  - BACKGROUND: Malnutrition is a common consequence of disease in older patients.
      Both in hospital setting and in community setting oral nutritional support has
      proven to be effective. However, cost-effectiveness studies are scarce.
      Therefore, the aim of our study is to investigate the effectiveness and cost
      effectiveness of transmural nutritional support in malnourished elderly patients,
      starting at hospital admission until three months after discharge. METHODS: This
      study is a randomized controlled trial. Patients are included at hospital
      admission and followed until three months after discharge. Patients are eligible
      to be included when they are > or = 60 years old and malnourished according to
      the following objective standards: Body Mass Index (BMI in kg/m2) < 20 and/or >
      or = 5% unintentional weight loss in the previous month and/or > or = 10%
      unintentional weight loss in the previous six months. We will compare usual
      nutritional care with transmural nutritional support (energy and protein enriched
      diet, two additional servings of an oral nutritional supplement, vitamin D and
      calcium supplementation, and consultations by a dietitian). Each study arm will
      consist of 100 patients. The primary outcome parameters will be changes in
      activities of daily living (determined as functional limitations and physical
      activity) between intervention and control group. Secondary outcomes will be
      changes in body weight, body composition, quality of life, and muscle strength.
      An economic evaluation from a societal perspective will be conducted alongside
      the randomised trial to evaluate the cost-effectiveness of the intervention in
      comparison with usual care. CONCLUSION: In this randomized controlled trial we
      will evaluate the effect of transmural nutritional support in malnourished
      elderly patients after hospital discharge, compared to usual care. Primary
      endpoints of the study are changes in activities of daily living, body weight,
      body composition, quality of life, and muscle strength. An economic evaluation
      will be performed to evaluate the cost-effectiveness of the intervention in
      comparison with usual care. TRIAL REGISTRATION: Netherlands Trial Register
      (ISRCTN29617677, registered 14-Sep-2005).

PMID- 20146795
TI  - Effects of worksite health promotion interventions on employee diets: a
      systematic review.
AB  - BACKGROUND: Public health strategies place increasing emphasis on opportunities
      to promote healthy behaviours within the workplace setting. Previous research has
      suggested worksite health promotion programmes have positive effects on physical
      activity and weight loss, yet little is known regarding their effects on dietary
      behaviour. The aim of this review was to assess the effects of worksite
      interventions on employee diets. METHODS: Electronic databases (MEDLINE, The
      Cochrane Library, PsycINFO, EMBASE, LexisNexis) were searched for relevant
      articles published between 1995 and April 2009. Studies were eligible for
      inclusion if they were peer-reviewed English language publications describing a
      worksite-based health promotion intervention with minimum study duration of eight
      weeks. All study designs were eligible. Studies had to report one or more diet
      related outcome (energy, fat, fruit, or vegetable intakes). Methodological
      quality was assessed using a checklist that included randomisation methods, use
      of a control group, and study attrition rates. RESULTS: Sixteen studies were
      included in the review. Eight programmes focussed on employee education, and the
      remainder targeted change to the worksite environment, either alone or in
      combination with education. Study methodological quality was moderate. In
      general, worksite interventions led to positive changes in fruit, vegetable and
      total fat intake. However, reliance on self-reported methods of dietary
      assessment means there is a significant risk of bias. No study measured more
      robust outcomes such as absenteeism, productivity, or healthcare utilisation.
      CONCLUSIONS: The findings of this review suggest that worksite health promotion
      programmes are associated with moderate improvement in dietary intake. The
      quality of studies to date has been frequently sub-optimal and further, well
      designed studies are needed in order to reliably determine effectiveness and cost
      effectiveness. Future programmes to improve employee dietary habits should move
      beyond individual education and aim to intervene at multiple levels of the
      worksite environment.

PMID- 20146796
TI  - Familial relative risks for breast cancer by pathological subtype: a population
      based cohort study.
AB  - INTRODUCTION: The risk of breast cancer to first degree relatives of breast
      cancer patients is approximately twice that of the general population. Breast
      cancer, however, is a heterogeneous disease and it is plausible that the familial
      relative risk (FRR) for breast cancer may differ by the pathological subtype of
      the tumour. The contribution of genetic variants associated with breast cancer
      susceptibility to the subtype-specific FRR is still unclear. METHODS: We computed
      breast cancer FRR for subtypes of breast cancer by comparing breast cancer
      incidence in relatives of breast cancer cases from a population-based series with
      known estrogen receptor (ER), progesterone receptor (PR) or human epidermal
      growth factor receptor 2 (HER2) status with that expected from the general
      population. We estimated the contribution to the FRR of genetic variants
      associated with breast cancer susceptibility using subtype-specific genotypic
      relative risks and allele frequencies for each variant. RESULTS: At least one
      marker was measured for 4,590 breast cancer cases, who reported 9,014 affected
      and unaffected first-degree female relatives. There was no difference between the
      breast cancer FRR for relatives of patients with ER-negative (FRR = 1.78, 95%
      confidence intervals (CI): 1.44 to 2.11) and ER-positive disease (1.82, 95% CI:
      1.67 to 1.98), P = 0.99. There was some suggestion that the breast cancer FRR for
      relatives of patients with ER-negative disease was higher than that for ER
      positive disease for ages of the relative less than 50 years old (FRR = 2.96, 95%
      CI: 2.04 to 3.87; and 2.05, 95% CI: 1.70 to 2.40 respectively; P = 0.07), and
      that the breast cancer FRR for relatives of patients with ER-positive disease was
      higher than for ER-negative disease when the age of the relative was greater than
      50 years (FRR = 1.76, 95% CI: 1.59 to 1.93; and 1.41, 95% CI: 1.08 to 1.74
      respectively, P = 0.06). We estimated that mutations in BRCA1 and BRCA2 explain
      32% of breast cancer FRR for relatives of patients with ER-negative and 9.4% of
      the breast cancer FRR for relatives of patients with ER-positive disease. Twelve
      recently identified common breast cancer susceptibility variants were estimated
      to explain 1.9% and 9.6% of the FRR to relatives of patients with ER-negative and
      ER-positive disease respectively. CONCLUSIONS: FRR for breast cancer was
      significantly increased for both ER-negative and ER-positive disease. Including
      receptor status in conjunction with genetic status may aid risk prediction in
      women with a family history.

PMID- 20146797
TI  - Identification and analysis of in planta expressed genes of Magnaporthe oryzae.
AB  - BACKGROUND: Infection of plants by pathogens and the subsequent disease
      development involves substantial changes in the biochemistry and physiology of
      both partners. Analysis of genes that are expressed during these interactions
      represents a powerful strategy to obtain insights into the molecular events
      underlying these changes. We have employed expressed sequence tag (EST) analysis
      to identify rice genes involved in defense responses against infection by the
      blast fungus Magnaporthe oryzae and fungal genes involved in infectious growth
      within the host during a compatible interaction. RESULTS: A cDNA library was
      constructed with RNA from rice leaves (Oryza sativa cv. Hwacheong) infected with
      M. oryzae strain KJ201. To enrich for fungal genes, subtraction library using PCR
      based suppression subtractive hybridization was constructed with RNA from
      infected rice leaves as a tester and that from uninfected rice leaves as the
      driver. A total of 4,148 clones from two libraries were sequenced to generate
      2,302 non-redundant ESTs. Of these, 712 and 1,562 ESTs could be identified to
      encode fungal and rice genes, respectively. To predict gene function, Gene
      Ontology (GO) analysis was applied, with 31% and 32% of rice and fungal ESTs
      being assigned to GO terms, respectively. One hundred uniESTs were found to be
      specific to fungal infection EST. More than 80 full-length fungal cDNA sequences
      were used to validate ab initio annotated gene model of M. oryzae genome
      sequence. CONCLUSION: This study shows the power of ESTs to refine genome
      annotation and functional characterization. Results of this work have advanced
      our understanding of the molecular mechanisms underpinning fungal-plant
      interactions and formed the basis for new hypothesis.

PMID- 20146798
TI  - Promotion of variant human mammary epithelial cell outgrowth by ionizing
      radiation: an agent-based model supported by in vitro studies.
AB  - INTRODUCTION: Most human mammary epithelial cells (HMEC) cultured from
      histologically normal breast tissues enter a senescent state termed stasis after
      5 to 20 population doublings. These senescent cells display increased size,
      contain senescence associated beta-galactosidase activity, and express cyclin
      dependent kinase inhibitor, p16INK4A (CDKN2A; p16). However, HMEC grown in a
      serum-free medium, spontaneously yield, at low frequency, variant (v) HMEC that
      are capable of long-term growth and are susceptible to genomic instability. We
      investigated whether ionizing radiation, which increases breast cancer risk in
      women, affects the rate of vHMEC outgrowth. METHODS: Pre-stasis HMEC cultures
      were exposed to 5 to 200 cGy of sparsely (X- or gamma-rays) or densely (1 GeV/amu
      56Fe) ionizing radiation. Proliferation (bromodeoxyuridine incorporation),
      senescence (senescence-associated beta-galactosidase activity), and p16
      expression were assayed in subcultured irradiated or unirradiated populations
      four to six weeks following radiation exposure, when patches of vHMEC became
      apparent. Long-term growth potential and p16 promoter methylation in subsequent
      passages were also monitored. Agent-based modeling, incorporating a simple set of
      rules and underlying assumptions, was used to simulate vHMEC outgrowth and
      evaluate mechanistic hypotheses. RESULTS: Cultures derived from irradiated cells
      contained significantly more vHMEC, lacking senescence associated beta
      galactosidase or p16 expression, than cultures derived from unirradiated cells.
      As expected, post-stasis vHMEC cultures derived from both unirradiated and
      irradiated cells exhibited more extensive methylation of the p16 gene than pre
      stasis HMEC cultures. However, the extent of methylation of individual CpG sites
      in vHMEC samples did not correlate with passage number or treatment. Exposure to
      sparsely or densely ionizing radiation elicited similar increases in the numbers
      of vHMEC compared to unirradiated controls. Agent-based modeling indicated that
      radiation-induced premature senescence of normal HMEC most likely accelerated
      vHMEC outgrowth through alleviation of spatial constraints. Subsequent
      experiments using defined co-cultures of vHMEC and senescent cells supported this
      mechanism. CONCLUSIONS: Our studies indicate that ionizing radiation can promote
      the outgrowth of epigenetically altered cells with pre-malignant potential.

PMID- 20146799
TI  - Signaling involved in neurite outgrowth of postnatally born subventricular zone
      neurons in vitro.
AB  - BACKGROUND: Neurite outgrowth is a key process during neuronal migration and
      differentiation. Complex intracellular signaling is involved in the initiation of
      neurite protrusion and subsequent elongation. Although, in general many
      constituents of the machinery involved in this multi-stage process are common for
      neurons in distinct brain areas, there are notable differences between specific
      neuronal subtypes. RESULTS: We analyzed key intracellular components of neurite
      outgrowth signaling in postnatally born subventricular zone (SVZ) neurons in
      vitro. We showed that inhibitors of PI3K, Akt1, PKCzeta and small GTPases
      significantly reduced neurite outgrowth. Transfection of SVZ-derived neurons with
      inactive forms of Rac1 or Cdc42 also decreased neurite length whereas
      transfection with constitutively active forms of Rac1, Cdc42 or Akt1 as well as
      with full-length PI3K or PKCzeta increased neurite length. PI3K, Akt1 and PKCzeta
      acted upstream of the small GTPases Rac1 and Cdc42, which in turn modulate
      lamellipodia formation of SVZ-derived neurons. CONCLUSION: We showed the
      involvement of PI3K/Akt1/PKCzeta/Rac1/Cdc42 pathway in neurite outgrowth of
      postnatally born SVZ neurons.

PMID- 20146800
TI  - Stability of large diffusion/perfusion mismatch in anterior circulation strokes
      for 4 or more hours.
AB  - BACKGROUND: The stability of hypoperfused brain tissue in stroke patients with
      major artery occlusions is unknown. The purpose of this study was to determine
      the persistence of a diffusion/perfusion mismatch in patients with ICA or
      proximal MCA occlusions. METHODS: Fourteen patients with ICA and/or proximal MCA
      occlusion and a diffusion/perfusion mismatch at presentation were studied. All
      were enrolled in a pilot randomized study of normobaric oxygen therapy. None
      received thrombolytic therapy; 8 received normobaric oxygen and 6 room air.
      Diffusion/perfusion MRI was performed at baseline, 4 hours, 24 hours, and 1 week.
      Abnormal DWI, ADC, and MTT volumes were determined using standard image analysis
      methods. RESULTS: The mean time from symptom onset to baseline MRI was 7.5 +/- 1
      hours. Across all 4 time points there was a significant difference in DWI lesion
      (ANOVA, P < 0.0001) and abnormal MTT volumes (ANOVA, P < 0.01) with the 24 hour
      and 1 week abnormal volumes different from the earlier studies. However,
      comparing baseline and 4 hour scans, there was no significant interval change in
      the mean abnormal DWI volume (29.4 +/- 8.2 ml vs. 28.1 +/- 7.4 ml) or abnormal
      MTT volumes (137 +/- 17.7 ml vs. 130.9 +/- 13.8). By 24 hours, only 2 patients
      did not maintain a mismatch of 20% or greater. CONCLUSIONS: Patients who present
      outside the time window for thrombolytic therapy, and who have a large
      diffusion/perfusion mismatch on MRI may have a stable mismatch for 4 or more
      hours.

PMID- 20146802
TI  - The application of item response theory on a teaching strategy profile
      questionnaire.
AB  - BACKGROUND: In medical education research, various questionnaires are often used
      to study possible relationships between strategies and approaches to teaching and
      learning and the outcome of these. However, judging the applicability of such
      questionnaires or the interpretation of the results is not trivial. METHODS: As a
      way to develop teacher thinking, teaching strategy profiles were calculated for
      teachers in a research intensive department at Karolinska Institutet. This study
      compares the sum score, that was inherent in the questionnaire used, with an Item
      Response Theory (IRT) approach. Three teaching dimensions were investigated and
      the intended sum scores were investigated by IRT analysis. RESULTS: Agreements as
      well as important differences were found. The use of the sum score seemed to
      agree reasonably with an IRT approach for two of the dimensions, while the third
      dimension could not be identified neither by a the sum score, nor by an IRT
      approach, as the items included showed conflicting messages. CONCLUSIONS: This
      study emphasizes the possibilities to gain better insight and more relevant
      interpretation of a questionnaire by use of IRT. A sum score approach should not
      be taken for granted. Its use has to be thoroughly evaluated.

PMID- 20146801
TI  - TAp73 is one of the genes responsible for the lack of response to chemotherapy
      depending on B-Raf mutational status.
AB  - BACKGROUND: Although there have been many studies on the p73 gene, some of its
      functions still remain unclear. There is little research on the relationship
      between p73 gene transcription and its protein expression and the response to
      certain drugs such as oxaliplatin and cetuximab, which are drugs currently used
      in colorectal cancer.The purpose of this study was to evaluate the impact of
      TAp73 expression on oxaliplatin and cetuximab-based chemotherapy in colorectal
      cancer cell lines with different K-Ras and B-Raf mutational status. METHODS:
      TAp73 was analyzed in three colorectal tumor cell lines HT-29, SW-480 and Caco-2.
      mRNA TAp73 was determined using Real time PCR; TAp73 protein by immunoblotting
      and cell viability was analyzed by the MTT method. RESULTS: We found that mRNA
      and TAp73 protein were decreased in cells treated with oxaliplatin (in
      monotherapy or combined with cetuximab) when B-Raf is mutated. This was
      statistically significant and was also associated with higher cell viability
      after the treatment. CONCLUSIONS: Here, for the first time we report, that there
      is a signaling loop between B-Raf activation and p73 function.Low expression of
      TAp73 in colorectal cancer cell lines with mutated B-Raf may be involved in the
      lack of response to oxaliplatin in monotherapy or combined with cetuximab.

PMID- 20146803
TI  - Evidence-based interventions in dementia: A pragmatic cluster-randomised trial of
      an educational intervention to promote earlier recognition and response to
      dementia in primary care (EVIDEM-ED).
AB  - BACKGROUND: The National Dementia Strategy seeks to enhance general
      practitioners' diagnostic and management skills in dementia. Early diagnosis in
      dementia within primary care is important as this allows those with dementia and
      their family care networks to engage with support services and plan for the
      future. There is, however, evidence that dementia remains under-detected and sub
      optimally managed in general practice. An earlier unblinded, cluster randomised
      controlled study tested the effectiveness of educational interventions in
      improving detection rates and management of dementia in primary care. In this
      original trial, a computer decision support system and practice-based educational
      workshops were effective in improving rates of detecting dementia although not in
      changing clinical management. The challenge therefore is to find methods of
      changing clinical management. Our aim in this new trial is to test a customised
      educational intervention developed for general practice, promoting both earlier
      diagnosis and concordance with management guidelines. DESIGN/METHOD: The
      customised educational intervention combines practice-based workshops and
      electronic support material. Its effectiveness will be tested in an unblinded
      cluster randomised controlled trial with a pre-post intervention design, with two
      arms; normal care versus the educational intervention. Twenty primary care
      practices have been recruited with the aim of gaining 200 patient participants.
      We will examine whether the intervention is effective, pragmatic and feasible
      within the primary care setting. Our primary outcome measure is an increase in
      the proportion of patients with dementia who receive at least two dementia
      specific management reviews per year. We will also examine important secondary
      outcomes such as practice concordance with management guidelines and benefits to
      patients and carers in terms of quality of life and carer strain. DISCUSSION: The
      EVIDEM-ED trial builds on the earlier study but the intervention is different in
      that it is specifically customised to the educational needs of each practice. If
      this trial is successful it could have implications for the implementation of the
      National Dementia Strategy. TRIAL REGISTRATION: NCT00866099.

PMID- 20146804
TI  - Suppressive and additive effects in protection mediated by combinations of
      monoclonal antibodies specific for merozoite surface protein 1 of Plasmodium
      yoelii.
AB  - BACKGROUND: The merozoite surface protein (MSP)-1 is a target antigen of
      protective immunity and a malaria vaccine candidate. The nature of this
      protective immune response warrants further investigation: although specific
      antibody is thought to play a major role, the mechanisms of protection are still
      unclear. Monoclonal antibodies (mAbs) specific for the C-terminus of MSP-1 from
      Plasmodium yoelii have been shown previously to provide protection against
      challenge infection when administered by passive immunization to mice. Three
      protective mAbs were re-examined and, in particular, the effect of combinations
      of antibodies on the protection provided was studied. It was found that a
      combination of two antibodies can either provide additive protective effects or
      result in a suppression of protection. In this report the importance of antibody
      subclass and epitope specificity in the outcome of these passive immunization
      experiments are discussed. METHODS: The minimum protective dose (MPD) for each
      mAb was determined, and then combinations of antibody at their MPD were
      investigated for their ability to control parasitaemia and promote survival in
      groups of mice. Mice were inoculated over three days with the MPD and challenged
      with a blood stage infection of the virulent P. yoelii 17 XL. The resultant
      parasitaemia was assessed daily on Giemsa-stained blood films. Following the
      infection the presence of MSP-1 specific antibodies in the sera was monitored,
      and the proliferative responses of cells in the spleen of protected mice were
      measured. RESULTS: Combining antibodies resulted in either an additive effect on
      protection, with reduced peak parasitaemia and better survival, or resulted in a
      suppression of protection over that achieved by a single antibody alone. An
      additive effect was observed when B6 and F5 that have the same isotype and
      similar fine specificity, were combined. However, a combination of mAb D3, an
      IgG2a, with either B6 or F5 (both IgG3) suppressed protection, an effect that may
      have been due to the combination of different isotypes or to the different fine
      specificity of the antibodies. CONCLUSIONS: These results suggest that a
      combination of protective antibodies with either the same or different isotypes
      can produce either an additive or a suppressive effect in passive immunization.
      This phenomenon may be important in better understanding immunity in this
      experimental mouse model of malaria.

PMID- 20146805
TI  - Genome-wide analysis of the diatom cell cycle unveils a novel type of cyclins
      involved in environmental signaling.
AB  - BACKGROUND: Despite the enormous importance of diatoms in aquatic ecosystems and
      their broad industrial potential, little is known about their life cycle control.
      Diatoms typically inhabit rapidly changing and unstable environments, suggesting
      that cell cycle regulation in diatoms must have evolved to adequately integrate
      various environmental signals. The recent genome sequencing of Thalassiosira
      pseudonana and Phaeodactylum tricornutum allows us to explore the molecular
      conservation of cell cycle regulation in diatoms. RESULTS: By profile-based
      annotation of cell cycle genes, counterparts of conserved as well as new
      regulators were identified in T. pseudonana and P. tricornutum. In particular,
      the cyclin gene family was found to be expanded extensively compared to that of
      other eukaryotes and a novel type of cyclins was discovered, the diatom-specific
      cyclins. We established a synchronization method for P. tricornutum that enabled
      assignment of the different annotated genes to specific cell cycle phase
      transitions. The diatom-specific cyclins are predominantly expressed at the G1-to
      S transition and some respond to phosphate availability, hinting at a role in
      connecting cell division to environmental stimuli. CONCLUSION: The discovery of
      highly conserved and new cell cycle regulators suggests the evolution of unique
      control mechanisms for diatom cell division, probably contributing to their
      ability to adapt and survive under highly fluctuating environmental conditions.

PMID- 20146806
TI  - A novel DSPP mutation causes dentinogenesis imperfecta type II in a large
      Mongolian family.
AB  - BACKGROUND: Several studies have shown that the clinical phenotypes of
      dentinogenesis imperfecta type II (DGI-II) may be caused by mutations in dentin
      sialophosphoprotein (DSPP). However, no previous studies have documented the
      clinical phenotype and genetic basis of DGI-II in a Mongolian family from China.
      METHODS: We identified a large five-generation Mongolian family from China with
      DGI-II, comprising 64 living family members of whom 22 were affected. Linkage
      analysis of five polymorphic markers flanking DSPP gene was used to genotype the
      families and to construct the haplotypes of these families. All five DSPP exons
      including the intron-exon boundaries were PCR-amplified and sequenced in 48
      members of this large family. RESULTS: All affected individuals showed
      discoloration and severe attrition of their teeth, with obliterated pulp chambers
      and without progressive high frequency hearing loss or skeletal abnormalities. No
      recombination was found at five polymorphic markers flanking DSPP in the family.
      Direct DNA sequencing identified a novel A-->G transition mutation adjacent to
      the donor splicing site within intron 3 in all affected individuals but not in
      the unaffected family members and 50 unrelated Mongolian individuals. CONCLUSION:
      This study identified a novel mutation (IVS3+3A-->G) in DSPP, which caused DGI-II
      in a large Mongolian family. This expands the spectrum of mutations leading to
      DGI-II.

PMID- 20146807
TI  - Ovarian cancer immunotherapy: opportunities, progresses and challenges.
AB  - Due to the low survival rates from invasive ovarian cancer, new effective
      treatment modalities are urgently needed. Compelling evidence indicates that the
      immune response against ovarian cancer may play an important role in controlling
      this disease. We herein summarize multiple immune-based strategies that have been
      proposed and tested for potential therapeutic benefit against advanced stage
      ovarian cancer. We will examine the evidence for the premise that an effective
      therapeutic vaccine against ovarian cancer is useful not only for inducing
      remission of the disease but also for preventing disease relapse. We will also
      highlight the questions and challenges in the development of ovarian cancer
      vaccines, and critically discuss the limitations of some of the existing
      immunotherapeutic strategies. Finally, we will summarize our own experience on
      the use of patient-specific tumor-derived heat shock protein-peptide complex for
      the treatment of advanced ovarian cancer.

PMID- 20146808
TI  - Argonaute proteins: potential biomarkers for human colon cancer.
AB  - BACKGROUND: Although Argonaute proteins are considered to play important roles in
      stem cell self-renewal, RNA interference (RNAi) and translational regulation,
      relatively little is known about their functions in human disease. In this study,
      we investigated the expression of eight members of human Argonaute family in
      colon cancer and identified their potential roles in tumor development and
      progression. METHODS: Antibodies against human Argonaute proteins were prepared
      by immunizing rabbits with synthetic peptides derived from the sequences of
      Argonaute members. Then we constructed a tissue microarray containing 75
      specimens from colon cancer and 75 specimens from adjacent non-cancer tissue, and
      assayed eight different proteins (EIF2C1, EIF2C2, EIF2C3, EIF2C4, PIWIL1, PIWIL2,
      PIWIL3 and PIWIL4) by immunohistochemistry on consecutive formalin-fixed tissue
      microarray sections. RESULTS: The expression of EIF2C1-4 and PIWIL1-4 was
      significantly higher in tumorous tissue than in adjacent tissue. Notably, a
      significant correlation was observed between the positive expression of EIF2C2,
      EIF2C3, EIF2C4, PIWIL4 and the presence of distant metastasis. Logistic
      regression analysis revealed that an increased expression of EIF2C1 and PIWIL2
      was significantly associated with occurrence of colon cancer tissue compared with
      non-cancer tissue. CONCLUSIONS: Argonaute proteins are overexpressed in colon
      cancer relative to adjacent non-cancer tissue. The expression of EIF2C2-4 and
      PIWIL4 appears increased in advanced tumors with distant metastasis, suggesting
      it may promote tumor invasion. Furthermore, EIF2C1 and PIWIL2 might represent
      novel colon cancer markers with early diagnostic significance.

PMID- 20146809
TI  - Probing the link between oestrogen receptors and oesophageal cancer.
AB  - BACKGROUND: Human oesophageal carcinoma is considered to be one of the most
      aggressive malignancies and has a very poor prognosis. The incidence of
      oesophageal cancer shows a gender bias and is higher in males compared with
      females, the ratio between males and females varying from 3:1 to 7:1. This sex
      ratio is not entirely attributable to differences in the prevalence of known risk
      factors between the sexes. The potential role of oestrogen receptors (ER) in
      oesophageal cancer has been debated for several years but the significance of the
      receptors in this cancer remains unknown. Most of the work has been based on
      immunohistochemistry and has not been validated with other available techniques.
      The inconsistencies in the published literature on the link between ER expression
      and oesophageal cancer warrant a thorough evaluation of the potential role of ERs
      in this malignancy. Even the expression of the two ER isoforms, ERalpha and
      ERbeta, and its implications for outcome of treatments in histological subtypes
      of oesophageal tumours is ill defined. The aim of this article is to provide
      updated information from the available literature on the current status of ER
      expression in oesophageal cancer and to discuss its potential therapeutic role.
      METHODS AND RESULTS: We performed a comprehensive literature search and analysed
      the results regarding ER expression in oesophageal tumours with special emphasis
      on expression of different oestrogen receptors and the role of sex hormones in
      oesophageal cancer. This article also focuses on the significance of the two main
      ER subtypes and mechanisms underlying the presumed male predominance of this
      disease. CONCLUSION: We postulate that differential oestrogen receptor status may
      be considered a biomarker of poor clinical outcome based on tissue
      dedifferentiation or advanced stage of the disease. Further, if we can establish
      the importance of oestrogen and its receptors in the context of oesophageal
      cancer, then this may lead to a new future direction in the management of this
      malignancy.

PMID- 20146810
TI  - A metabolic signature of long life in Caenorhabditis elegans.
AB  - BACKGROUND: Many Caenorhabditis elegans mutations increase longevity and much
      evidence suggests that they do so at least partly via changes in metabolism.
      However, up until now there has been no systematic investigation of how the
      metabolic networks of long-lived mutants differ from those of normal worms.
      Metabolomic technologies, that permit the analysis of many untargeted metabolites
      in parallel, now make this possible. Here we use one of these, 1H nuclear
      magnetic resonance spectroscopy, to investigate what makes long-lived worms
      metabolically distinctive. RESULTS: We examined three classes of long-lived
      worms: dauer larvae, adult Insulin/IGF-1 signalling (IIS)-defective mutants, and
      a translation-defective mutant. Surprisingly, these ostensibly different long
      lived worms share a common metabolic signature, dominated by shifts in
      carbohydrate and amino acid metabolism. In addition the dauer larvae, uniquely,
      had elevated levels of modified amino acids (hydroxyproline and phosphoserine).
      We interrogated existing gene expression data in order to integrate functional
      (metabolite-level) changes with transcriptional changes at a pathway level.
      CONCLUSIONS: The observed metabolic responses could be explained to a large
      degree by upregulation of gluconeogenesis and the glyoxylate shunt as well as
      changes in amino acid catabolism. These responses point to new possible
      mechanisms of longevity assurance in worms. The metabolic changes observed in
      dauer larvae can be explained by the existence of high levels of autophagy
      leading to recycling of cellular components.See associated minireview:
      http://jbiol.com/content/9/1/7.

PMID- 20146811
TI  - New method of measuring wrist joint position sense avoiding cutaneous and visual
      inputs.
AB  - BACKGROUND: Aspects of afferent inputs, generally termed proprioception, are
      being increasingly studied. Extraneous factors such as cutaneous inputs can
      dramatically interfere while trying to design studies in order to determine the
      participation of the different structures involved in proprioception in the wrist
      position sense. We tried to determine validity and repeatability of a new wrist
      joint position measurement device using methodology designed to minimize
      extraneous factors and isolate muscle and joint inputs. METHODS: In order to test
      the reliability of the system, eighty young-adult subjects without
      musculoskeletal or neurologic impairments affecting the right upper extremity
      were tested using a custom made motion tracking system. Testing consisted of two
      conditions: active reproduction of active placement and passive reproduction of
      passive placement. Subjects performed two repetitions of each target position
      (10, 20, and 30 degrees of flexion and extension) presented in a random order.
      Test- retest reliability was then tested. RESULTS: The average constant error in
      the passive condition was -0.7 degrees +/- 4.7 degrees as compared to the active
      condition at 3.7 degrees +/- 5.1 degrees. Average absolute error in the passive
      condition was 4.9 degrees +/- 2.9 degrees compared to the active condition in
      which absolute error was 5.9 degrees +/- 3.5 degrees. DISCUSSION: Test-retest
      repeatability in both conditions was less than the 5 degrees magnitude typical of
      clinical goniometry. Errors in the active condition (less than 2 degrees ) were
      slightly smaller than the passive condition, and the passive condition was also
      associated with poorer consistency between apparatus sensors and skin sensors.
      CONCLUSIONS: The current system for measurement of wrist joint proprioception
      allows the researcher to decrease extraneous influences that may affect joint
      position sense awareness, and will help in future study aiming to determine
      precisely the role of the different structure involved in proprioception.

PMID- 20146812
TI  - Identification of lung cancer with high sensitivity and specificity by blood
      testing.
AB  - BACKGROUND: Lung cancer is a very frequent and lethal tumor with an identifiable
      risk population. Cytological analysis and chest X-ray failed to reduce mortality,
      and CT screenings are still controversially discussed. Recent studies provided
      first evidence for the potential usefulness of autoantigens as markers for lung
      cancer. METHODS: We used extended panels of arrayed antigens and determined
      autoantibody signatures of sera from patients with different kinds of lung
      cancer, different common non-tumor lung pathologies, and controls without any
      lung disease by a newly developed computer aided image analysis procedure. The
      resulting signatures were classified using linear kernel Support Vector Machines
      and 10-fold cross-validation. RESULTS: The novel approach allowed for
      discriminating lung cancer patients from controls without any lung disease with a
      specificity of 97.0%, a sensitivity of 97.9%, and an accuracy of 97.6%. The
      classification of stage IA/IB tumors and controls yielded a specificity of 97.6%,
      a sensitivity of 75.9%, and an accuracy of 92.9%. The discrimination of lung
      cancer patients from patients with non-tumor lung pathologies reached an accuracy
      of 88.5%. CONCLUSION: We were able to separate lung cancer patients from subjects
      without any lung disease with high accuracy. Furthermore, lung cancer patients
      could be separated from patients with other non-tumor lung diseases. These
      results provide clear evidence that blood-based tests open new avenues for the
      early diagnosis of lung cancer.

PMID- 20146813
TI  - High-throughput detection of mutations responsible for childhood hearing loss
      using resequencing microarrays.
AB  - BACKGROUND: Despite current knowledge of mutations in 45 genes that can cause
      nonsyndromic sensorineural hearing loss (SNHL), no unified clinical test has been
      developed that can comprehensively detect mutations in multiple genes. We
      therefore designed Affymetrix resequencing microarrays capable of resequencing 13
      genes mutated in SNHL (GJB2, GJB6, CDH23, KCNE1, KCNQ1, MYO7A, OTOF, PDS, MYO6,
      SLC26A5, TMIE, TMPRSS3, USH1C). We present results from hearing loss arrays
      developed in two different research facilities and highlight some of the
      approaches we adopted to enhance the applicability of resequencing arrays in a
      clinical setting. RESULTS: We leveraged sequence and intensity pattern features
      responsible for diminished coverage and accuracy and developed a novel algorithm,
      sPROFILER, which resolved >80% of no-calls from GSEQ and allowed 99.6% (range:
      99.2-99.8%) of sequence to be called, while maintaining overall accuracy at
      >99.8% based upon dideoxy sequencing comparison. CONCLUSIONS: Together, these
      findings provide insight into critical issues for disease-centered resequencing
      protocols suitable for clinical application and support the use of array-based
      resequencing technology as a valuable molecular diagnostic tool for pediatric
      SNHL and other genetic diseases with substantial genetic heterogeneity.

PMID- 20146814
TI  - Development of a toxR-based loop-mediated isothermal amplification assay for
      detecting Vibrio parahaemolyticus.
AB  - BACKGROUND: Vibrio parahaemolyticus is a leading cause of seafood-related
      bacterial gastroenteritis and outbreaks worldwide. Sensitive and specific
      detection methods are needed to better control V. parahaemolyticus infections.
      This study aimed at developing a highly specific and sensitive loop-mediated
      isothermal amplification (LAMP) assay for detecting V. parahaemolyticus in
      oysters. A set of five LAMP primers, two outer, two inner, and one loop were
      designed based on the published V. parahaemolyticus toxR sequence. Specificity of
      the assay was evaluated using a panel of 36 V. parahaemolyticus and 39 other
      strains. The assay sensitivity was determined using serial dilutions of V.
      parahaemolyticus ATCC 27969 culture ranging from 10(8) CFU/ml to extinction. The
      assay was also tested in experimentally inoculated oyster samples. RESULTS: The
      toxR-based LAMP assay was able to specifically detect all of the 36 V.
      parahaemolyticus strains without amplification from 39 other strains. The
      detection limit was 47-470 cells per reaction in pure culture, up to 100-fold
      more sensitive than that of toxR-PCR. When applied in spiked oysters, the assay
      was able to detect 1.1 x 10(5) V. parahaemolyticus cells per gram of oyster
      without enrichment, up to 100-fold more sensitive than that of toxR-PCR. Standard
      curves generated for detecting V. parahaemolyticus in both pure culture and
      spiked oyster samples showed good linear relationship between cell numbers and
      the fluorescence or turbidity signals. CONCLUSIONS: The toxR-based LAMP assay
      developed in this study was sensitive, specific, and quantitative, holding great
      potential for future field detection of V. parahaemolyticus in raw oysters.

PMID- 20146815
TI  - African meningitis belt pneumococcal disease epidemiology indicates a need for an
      effective serotype 1 containing vaccine, including for older children and adults.
AB  - BACKGROUND: Pneumococcal conjugate vaccine strategies in GAVI-eligible countries
      are focusing on infant immunization but this strategy may not be optimal in all
      settings. We aimed to collect all available population based data on pneumococcal
      meningitis throughout life in the African meningitis belt and then to model
      overall meningitis risk to help inform vaccine policy. METHODS: After a
      systematic review of literature published from 1970 through the present, we found
      robust population-based Streptococcus pneumoniae (Sp) meningitis data across age
      strata for four African meningitis belt countries that included 35 surveillance
      years spanning from 1970 to 2005. Using these data we modeled disease risk for a
      hypothetical cohort of 100,000 persons followed throughout life. RESULTS: Similar
      to meningococcal meningitis, laboratory-confirmed pneumococcal meningitis was
      seasonal, occurring primarily in the dry season. The mean annual Sp meningitis
      incidence rates were 98, 7.8 to 14, and 5.8 to 12 per 100,000 among persons <1, 1
      through 19, and 20 to 99 years of age, respectively, which (in the absence of
      major epidemics) were higher than meningococcal meningitis incidences for persons
      less than 1 and over 20 years of age. Mean Sp meningitis case fatality ratios
      (CFR) among hospitalized patients ranged from 36-66% depending on the age group,
      with CFR exceeding 60% for all age groups beyond 40 years; depending on the age
      group, Sp meningitis mortality incidences were 2 to 12-fold greater than those
      for meningococcal meningitis. The lifetime risks of pneumococcal meningitis
      disease and death were 0.6% (1 in 170) and 0.3% (1 in 304), respectively. The
      incidences of these outcomes were highest among children age <1 year. However,
      the cumulative risk was highest among persons age 5 to 59 years who experienced
      59% of pneumococcal meningitis outcomes. After age 5 years and depending on the
      country, 59-79% of meningitis cases were caused by serotype 1. CONCLUSIONS: In
      the African meningitis belt, Sp is as important a cause of meningitis as
      Neisseria meningitidis, particularly among older children and working age adults.
      The meningitis belt population needs an effective serotype 1 containing vaccine
      and policy discussions should consider vaccine use outside of early childhood.

PMID- 20146816
TI  - A versatile polyacrylamide gel electrophoresis based sulfotransferase assay.
AB  - BACKGROUND: Sulfotransferases are a large group of enzymes that regulate the
      biological activity or availability of a wide spectrum of substrates through
      sulfation with the sulfur donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS).
      These enzymes are known to be difficult to assay. A convenient assay is needed in
      order to better understand these enzymes. RESULTS: A universal sulfotransferase
      assay method based on sodium dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE) is described. This assay has been successfully applied to substrates
      as small as alpha-naphthol and as big as proteoglycans. As examples, we present
      the assays for recombinant human CHST4, TPST1, CHST3 and HS6ST1. In order to
      assess whether a small molecule can be applicable to this type of assay, a method
      to estimate the relative mobility of a molecule to PAPS is also presented. The
      estimated relative mobilities of various sulfated small molecules generated by
      SULT1A1, SULT1E1, SULT2A1 and CHST4 are in the range of +/- 0.2 of the actual
      relative mobilities. CONCLUSION: The versatility of the current method comes from
      the ability that SDS-PAGE can separate proteins and small molecules according to
      different parameters. While mobilities of proteins during SDS-PAGE are inversely
      related to their sizes, mobilities of small molecules are positively related to
      their charge/mass ratios. The predicted relative mobility of a product to PAPS is
      a good indicator of whether a sulfotransferase can be assayed with SDS-PAGE.
      Because phosphorylation is most similar to sulfation in chemistry, the method is
      likely to be applicable to kinases as well.

PMID- 20146817
TI  - The cell envelope subtilisin-like proteinase is a virulence determinant for
      Streptococcus suis.
AB  - BACKGROUND: Streptococcus suis is a major swine pathogen and zoonotic agent that
      mainly causes septicemia, meningitis, and endocarditis. It has recently been
      suggested that proteinases produced by S. suis (serotype 2) are potential
      virulence determinants. In the present study, we screened a S. suis mutant
      library created by the insertion of Tn917 transposon in order to isolate a mutant
      deficient in a cell surface proteinase. We characterized the gene and assessed
      the proteinase for its potential as a virulence factor. RESULTS: Two mutants (G6G
      and M3G) possessing a single Tn917 insertion were isolated. The affected gene
      coded for a protein (SSU0757) that shared a high degree of identity with
      Streptococccus thermophilus PrtS (95.9%) and, to a lesser extent, with
      Streptococcus agalactiae CspA (49.5%), which are cell surface serine proteinases.
      The SSU0757 protein had a calculated molecular mass of 169.6 kDa and contained
      the catalytic triad characteristic of subtilisin family proteinases: motif I
      (Asp200), motif II (His239), and motif III (Ser568). SSU0757 also had the Gram
      positive cell wall anchoring motif (Leu-Pro-X-Thr-Gly) at the carboxy-terminus,
      which was followed by a hydrophobic domain. All the S. suis isolates tested,
      which belonged to different serotypes, possessed the gene encoding the SSU0757
      protein. The two mutants devoid of subtilisin-like proteinase activity had longer
      generation times and were more susceptible to killing by whole blood than the
      wild-type parent strain P1/7. The virulence of the G6G and M3G mutants was
      compared to the wild-type strain in the CD1 mouse model. Significant differences
      in mortality rates were noted between the P1/7 group and the M3G and G6G groups
      (p < 0.001). CONCLUSION: In summary, we identified a gene coding for a cell
      surface subtilisin-like serine proteinase that is widely distributed in S. suis.
      Evidences were brought for the involvement of this proteinase in S. suis
      virulence.

PMID- 20146818
TI  - The tuberculosis challenge in a rural South African HIV programme.
AB  - BACKGROUND: South Africa remains the country with the greatest burden of HIV
      infected individuals and the second highest estimated TB incidence per capita
      worldwide. Within South Africa, KwaZulu-Natal has one of the highest rates of TB
      incidence and an emerging epidemic of drug-resistant tuberculosis. METHODS:
      Review of records of consecutive HIV-infected people initiated onto ART between
      1st January 2005 and 31st March 2006. Patients were screened for TB at initiation
      and incident episodes recorded. CD4 counts, viral loads and follow-up status were
      recorded; data was censored on 5th August 2008. Geographic cluster analysis was
      performed using spatial scanning. RESULTS: 801 patients were initiated. TB
      prevalence was 25.3%, associated with lower CD4 (AHR 2.61 p = 0.01 for CD4 <50
      cells/microl) and prior TB (AHR 1.58 p = 0.02). Incidence was 6.89 per 100 person
      years from 81 cases over 1175 person-years analysis time and was highest in the
      first 3 months after ART initiation; associated with male sex and higher log HIV
      RNA. Prevalent and incident TB were significantly associated with mortality (OR
      1.81 p = 0.01 and 2.02 p = 0.01 respectively). Incident TB was associated with a
      non-significant trend towards viral load >25 copies/ml (OR 1.75 p = 0.11). A low
      risk cluster for incident TB was identified for patients living near the local
      hospital in the geospatial analysis. CONCLUSION: There is a large burden of TB in
      this population. Rate of incident TB stabilises at a rate higher than that of the
      overall population. These data highlight the need for greater research on
      strategies for active case finding in rural settings and the need to focus on
      strengthening primary health care.

PMID- 20146819
TI  - International health policy survey in 11 countries: assessment of non-response
      bias in the Norwegian sample.
AB  - BACKGROUND: International health policy surveys are used to compare and evaluate
      health system performance, but little is known about the effects of non-response.
      The objective of this study was to assess the effects of non-response in the
      Norwegian part of the Commonwealth Fund international health policy survey in
      2009. METHODS: As part of an international health policy survey in 2009 a cross
      sectional survey was conducted in Norway among a representative sample of
      Norwegian general practitioners. 1,400 randomly selected GPs were sent a postal
      questionnaire including questions about the Norwegian health care system, the
      quality of the GPs' own practice and the cooperation with specialist health care.
      The survey included three postal reminders and a telephone follow-up of postal
      non-respondents. The main outcome measures were increase in response rate for
      each reminder, the effects of demographic and practice variables on response, the
      effects of non-response on survey estimates, and the cost-effectiveness of each
      reminder. RESULTS: After three postal reminders and one telephone follow-up, the
      response rate was 59.1%. Statistically significant differences between
      respondents and non-respondents were found for three variables; group vs. solo
      practice (p = 0.01), being a specialist or not (p < 0.001) and municipality
      centrality (least central vs. most central, p = 0.03). However, demographic and
      practice variables had little association with five outcome variables and the
      overall survey estimates changed little with additional reminders. In addition,
      the cost-effectiveness of the final reminders was poor. CONCLUSIONS: The response
      rate in the Norwegian survey was satisfactory, and the effect of non-response was
      small indicating adequate representativeness. The cost-effectiveness of the final
      reminders was poor. The Norwegian findings strengthen the international project,
      but restrictions in generalizability warrant further study in other countries.

PMID- 20146820
TI  - Documentation of best interest by intensivists: a retrospective study in an
      Ontario critical care unit.
AB  - BACKGROUND: Intensive care physicians often must rely on substitute decision
      makers to address all dimensions of the construct of "best interest" for
      incapable, critically ill patients. This task involves identifying prior wishes
      and to facilitate the substitute decision maker's understanding of the incapable
      patient's condition and their likely response to treatment. We sought to
      determine how well such discussions are documented in a typical intensive care
      unit. METHODS: Using a quality of communication instrument developed from a
      literature search and expert opinion, 2 investigators transcribed and analyzed
      260 handwritten communications for 105 critically ill patients who died in the
      intensive care unit between January and June 2006. Cohen's kappa was calculated
      before analysis and then disagreements were resolved by consensus. We report
      results on a per-patient basis to represent documented communication as a process
      leading up to the time of death in the ICU. We report frequencies and percentages
      for discrete data, median (m) and interquartile range (IQR) for continuous data.
      RESULTS: Our cohort was elderly (m 72, IQR 58-81 years) and had high APACHE II
      scores predictive of a high probability of death (m 28, IQR 23-36). Length of
      stay in the intensive care unit prior to death was short (m 2, IQR 1-5 days), and
      withdrawal of life support preceded death for more than half (n 57, 54%). Brain
      death criteria were present for 18 patients (17%). Although intensivists'
      communications were timely (median 17 h from admission to critical care), the
      person consenting on behalf of the incapable patient was explicitly documented
      for only 10% of patients. Life support strategies at the time of communication
      were noted in 45% of charts, and options for their future use were presented in
      88%. Considerations relevant to determining the patient's best interest in
      relation to the treatment plan were not well documented. While explicit survival
      estimates were noted in 50% of charts, physicians infrequently documented their
      own predictions of the patient's functional status (20%), anticipated need for
      chronic care (0%), or post ICU quality of life (3%). Similarly, documentation of
      the patient's own perspectives on these ranged from 2-18%. CONCLUSIONS:
      Intensivists' documentation of their communication with substitute decision
      makers frequently outlined the proposed plan of treatment, but often lacked
      evidence of discussion relevant to whether the treatment plan was expected to
      improve the patient's condition. Legislative standards for determination of best
      interest, such as the Health Care Consent Act in Ontario, Canada, may provide
      guidance for intensivists to optimally document the rationales for proposed
      treatment plans.

PMID- 20146821
TI  - Standardized observation of neighbourhood disorder: does it work in Canada?
AB  - BACKGROUND: There is a growing body of evidence that where you live is important
      to your health. Despite numerous previous studies investigating the relationship
      between neighbourhood deprivation (and structure) and residents' health, the
      precise nature of this relationship remains unclear. Relatively few
      investigations have relied on direct observation of neighbourhoods, while those
      that have were developed primarily in US settings. Evaluation of the
      transferability of such tools to other contexts is an important first step before
      applying such instruments to the investigation of health and well-being. This
      study evaluated the performance of a systematic social observational (SSO) tool
      (adapted from previous studies of American and British neighbourhoods) in a
      Canadian urban context. METHODS: This was a mixed-methods study. Quantitative SSO
      ratings and qualitative descriptions of 176 block faces were obtained in six
      Toronto neighbourhoods (4 low-income, and 2 middle/high-income) by trained
      raters. Exploratory factor analysis was conducted with the quantitative SSO
      ratings. Content analysis consisted of independent coding of qualitative data by
      three members of the research team to yield common themes and categories.
      RESULTS: Factor analysis identified three factors (physical decay/disorder,
      social accessibility, recreational opportunities), but only 'physical
      decay/disorder' reflected previous findings in the literature. Qualitative
      results (based on raters' fieldwork experiences) revealed the tool's shortcomings
      in capturing important features of the neighbourhoods under study, and informed
      interpretation of the quantitative findings. CONCLUSIONS: This study tested the
      performance of an SSO tool in a Canadian context, which is an important initial
      step before applying it to the study of health and disease. The tool demonstrated
      important shortcomings when applied to six diverse Toronto neighbourhoods. The
      study's analyses challenge previously held assumptions (e.g. social 'disorder')
      regarding neighbourhood social and built environments. For example, neighbourhood
      'order' has traditionally been assumed to be synonymous with a certain degree of
      homogeneity, however the neighbourhoods under study were characterized by high
      degrees of heterogeneity and low levels of disorder. Heterogeneity was seen as an
      appealing feature of a block face. Employing qualitative techniques with SSO
      represents a unique contribution, enhancing both our understanding of the
      quantitative ratings obtained and of neighbourhood characteristics that are not
      currently captured by such instruments.

PMID- 20146822
TI  - Identification and functional characterisation of Complement Regulator Acquiring
      Surface Protein-1 of serum resistant Borrelia garinii OspA serotype 4.
AB  - BACKGROUND: B. burgdorferi sensu lato (sl) is the etiological agent of Lyme
      borreliosis in humans. Spirochetes have adapted themselves to the human immune
      system in many distinct ways. One important immune escape mechanism for evading
      complement activation is the binding of complement regulators Factor H (CFH) or
      Factor H-like protein1 (FHL-1) to Complement Regulator-Acquiring Surface Proteins
      (CRASPs). RESULTS: We demonstrate that B. garinii OspA serotype 4 (ST4) PBi
      resist complement-mediated killing by binding of FHL-1. To identify the primary
      ligands of FHL-1 four CspA orthologs from B. garinii ST4 PBi were cloned and
      tested for binding to human CFH and FHL-1. Orthologs BGA66 and BGA71 were found
      to be able to bind both complement regulators but with different intensities. In
      addition, all CspA orthologs were tested for binding to mammalian and avian CFH.
      Distinct orthologs were able to bind to CFH of different animal origins.
      CONCLUSIONS: B. garinii ST4 PBi is able to evade complement killing and it can
      bind FHL-1 to membrane expressed proteins. Recombinant proteins BGA66 can bind
      FHL-1 and human CFH, while BGA71 can bind only FHL-1. All recombinant CspA
      orthologs from B. garinii ST4 PBi can bind CFH from different animal origins.
      This partly explains the wide variety of animals that can be infected by B.
      garinii.

PMID- 20146823
TI  - Sequential chemotherapy and intensity-modulated radiation therapy in the
      management of locoregionally advanced nasopharyngeal carcinoma: experience of 370
      consecutive cases.
AB  - INTRODUCTION: To investigate the outcome of locoregionally advanced
      nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy
      (IMRT) after induction chemotherapy, with or without concomitant chemotherapy.
      METHODS: Between August 2003 and March 2007, 370 patients with locoregionally
      advanced NPC were treated with IMRT. Presenting stages were stage IIB in 62,
      stage III in 197, and stage IVA/B in 111 patients. All patients except for 36
      patients with cervical lymphadenopathy of 4 cm or less in diameter received 2
      cycles of cisplatin-based neoadjuvant chemotherapy. Forty-eight patients received
      cisplatin-based concurrent chemotherapy as well. RESULTS: With a median follow-up
      time of 31 months (range 5 to 61 months), the 3-year local control, regional
      control, metastasis-free survival (MFS), disease-free survival (DFS) and overall
      survival (OS) rates were 95%, 97%, 86%, 81% and 89%, respectively. Multivariate
      analyses revealed that both age (< or = 60 vs. >60) and N-classification are
      significant prognosticators for OS (P = 0.001, hazard ratio [HR] 2.395, 95%
      confidence interval [CI] 1.432-4.003; P = 0.012, hazard ratio [HR] 2.614, 95%
      confidence interval [CI] 1.235-5.533); And N-classification is the only
      significant predicative factor for MFS (P = 0.002, [HR] 1.99, 95% CI 1.279
      3.098). T-classification and concurrent chemotherapy were not significant
      prognostic factors for local/regional control, MFS, DFS, or OS. Subgroup analysis
      revealed that concurrent chemotherapy provided no significant benefit to IMRT in
      locoregionally advanced NPC, but was responsible for higher rates of grade 3 or 4
      acute toxicities (50% vs. 29.8%, P < 0.005). No grade 3 or 4 late toxicity
      including xerostomia was observed. However, two patients treated with IMRT and
      neoadjuvant but without concurrent and adjuvant chemotherapy died of treatment
      related complications. CONCLUSION: IMRT following neoadjuvant chemotherapy
      produced a superb outcome in terms of local control, regional control, MFS, DFS,
      and OS rates in patients with stage IIB to IVB NPC. Effective treatment strategy
      is urgently needed for distant control in patients diagnosed with locoregionally
      advanced NPC.

PMID- 20146824
TI  - Fungal secretome database: integrated platform for annotation of fungal
      secretomes.
AB  - BACKGROUND: Fungi secrete various proteins that have diverse functions.
      Prediction of secretory proteins using only one program is unsatisfactory. To
      enhance prediction accuracy, we constructed Fungal Secretome Database (FSD).
      DESCRIPTION: A three-layer hierarchical identification rule based on nine
      prediction programs was used to identify putative secretory proteins in 158
      fungal/oomycete genomes (208,883 proteins, 15.21% of the total proteome). The
      presence of putative effectors containing known host targeting signals such as
      RXLX [EDQ] and RXLR was investigated, presenting the degree of bias along with
      the species. The FSD's user-friendly interface provides summaries of prediction
      results and diverse web-based analysis functions through Favorite, a personalized
      repository. CONCLUSIONS: The FSD can serve as an integrated platform supporting
      researches on secretory proteins in the fungal kingdom. All data and functions
      described in this study can be accessed on the FSD web site at
      http://fsd.snu.ac.kr/.

PMID- 20146825
TI  - Using machine learning to speed up manual image annotation: application to a 3D
      imaging protocol for measuring single cell gene expression in the developing C.
      elegans embryo.
AB  - BACKGROUND: Image analysis is an essential component in many biological
      experiments that study gene expression, cell cycle progression, and protein
      localization. A protocol for tracking the expression of individual C. elegans
      genes was developed that collects image samples of a developing embryo by 3-D
      time lapse microscopy. In this protocol, a program called StarryNite performs the
      automatic recognition of fluorescently labeled cells and traces their lineage.
      However, due to the amount of noise present in the data and due to the challenges
      introduced by increasing number of cells in later stages of development, this
      program is not error free. In the current version, the error correction (i.e.,
      editing) is performed manually using a graphical interface tool named AceTree,
      which is specifically developed for this task. For a single experiment, this
      manual annotation task takes several hours. RESULTS: In this paper, we reduce the
      time required to correct errors made by StarryNite. We target one of the most
      frequent error types (movements annotated as divisions) and train a support
      vector machine (SVM) classifier to decide whether a division call made by
      StarryNite is correct or not. We show, via cross-validation experiments on
      several benchmark data sets, that the SVM successfully identifies this type of
      error significantly. A new version of StarryNite that includes the trained SVM
      classifier is available at http://starrynite.sourceforge.net. CONCLUSIONS: We
      demonstrate the utility of a machine learning approach to error annotation for
      StarryNite. In the process, we also provide some general methodologies for
      developing and validating a classifier with respect to a given pattern
      recognition task.

PMID- 20146826
TI  - Leukotriene B4, administered via intracerebroventricular injection, attenuates
      the antigen-induced asthmatic response in sensitized guinea pigs.
AB  - BACKGROUND: Despite intensive studies focused on the pathophysiology of asthmatic
      inflammation, little is known about how cross-talk between neuroendocrine and
      immune systems regulates the inflammatory response during an asthmatic attack. We
      recently showed corresponding changes of cytokines and leukotriene B4 (LTB4) in
      brain and lung tissues of antigen-challenged asthmatic rats. Here, we
      investigated how LTB4 interacts with the neuroendocrine-immune system in
      regulating antigen-induced asthmatic responses in sensitized guinea pigs.
      METHODS: Ovalbumin-sensitized guinea pigs were challenged by inhalation of
      antigen. Vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor) was
      given via intracerebroventricular injection (i.c.v.) 30 min before challenge.
      Airway contraction response was evaluated using Penh values before and after
      antigen challenge. The inflammatory response in lung tissue was evaluated 24 h
      after challenge. The LTB4 content of lung and brain homogenate preparations was
      detected by reversed phase high-performance liquid chromatography (RP-HPLC).
      Plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT)
      were measured using ELISA kits. RESULTS: Antigen challenge impaired pulmonary
      function and increased inflammatory cell infiltration in lung tissue. These
      responses could be significantly suppressed by LTB4, 30 ng i.c.v., in ovalbumin
      sensitized guinea pigs. LTB4 content of lung and brain homogenates from antigen
      challenged guinea pigs was significantly increased. In addition, administration
      of LTB4 via i.c.v. markedly increased CORT and ACTH level in plasma before
      antigen challenge, and there were further increases in CORT and ACTH levels in
      plasma after antigen challenge. U75302, 100 ng i.c.v., completely blocked the
      effects of LTB4. In addition, U75302, 100 ng via i.c.v. injection, markedly
      decreased LTB4 content in lung homogenates, but not in brain homogenates.
      CONCLUSIONS: Increased LTB4 levels in brain during asthmatic attacks down
      regulates airway contraction response and inflammation through the BLT1 receptor.
      Stimulation of the hypothalamic-pituitary-adrenal axis by LTB4 may result in an
      increase in systemic glucocorticoids which, in turn, would feed back to suppress
      the asthmatic response.

PMID- 20146827
TI  - Role of apoptosis-inducing factor (AIF) in programmed nuclear death during
      conjugation in Tetrahymena thermophila.
AB  - BACKGROUND: Programmed nuclear death (PND), which is also referred to as nuclear
      apoptosis, is a remarkable process that occurs in ciliates during sexual
      reproduction (conjugation). In Tetrahymena thermophila, when the new macronucleus
      differentiates, the parental macronucleus is selectively eliminated from the
      cytoplasm of the progeny, concomitant with apoptotic nuclear events. However, the
      molecular mechanisms underlying these events are not well understood. The
      parental macronucleus is engulfed by a large autophagosome, which contains
      numerous mitochondria that have lost their membrane potential. In animals,
      mitochondrial depolarization precedes apoptotic cell death, which involves DNA
      fragmentation and subsequent nuclear degradation. RESULTS: We focused on the role
      of mitochondrial apoptosis-inducing factor (AIF) during PND in Tetrahymena. The
      disruption of AIF delays the normal progression of PND, specifically, nuclear
      condensation and kilobase-size DNA fragmentation. AIF is localized in Tetrahymena
      mitochondria and is released into the macronucleus prior to nuclear condensation.
      In addition, AIF associates and co-operates with the mitochondrial DNase to
      facilitate the degradation of kilobase-size DNA, which is followed by
      oligonucleosome-size DNA laddering. CONCLUSIONS: Our results suggest that
      Tetrahymena AIF plays an important role in the degradation of DNA at an early
      stage of PND, which supports the notion that the mitochondrion-initiated
      apoptotic DNA degradation pathway is widely conserved among eukaryotes.

PMID- 20146828
TI  - Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in
      Indian males: a preliminary study.
AB  - BACKGROUND: Dopamine is an important neurotransmitter involved in reward
      mechanism in the brain and thereby influences development and relapse of alcohol
      dependence. The dopamine D2 receptor (DRD2) gene on chromosome 11 (q22-q23) has
      been found to be associated with increased alcohol consumption through mechanisms
      involving incentive salience attributions and craving in alcoholic patients.
      Therefore, we investigated the association of three single nucleotide
      polymorphisms (SNP) in DRD2 gene with alcohol dependence in the north Indian
      subjects. METHODS: In a retrospective analysis, genetic association of three
      polymorphisms from DRD2 gene with alcohol dependence was investigated using a
      case-control approach. Alcohol dependence was determined by DSM-IV criteria and a
      total of 90 alcoholics and 60 healthy unrelated age-matched control subjects were
      recruited. Odds ratio and confidence interval was calculated to determine risk
      conferred by a predisposing allele/genotype/haplotype. Logistic regression
      analysis was carried out to correlate various clinical parameters with genotypes,
      and to study pair-wise interactions between SNPs. RESULTS: The study showed a
      significant association of -141C Ins allele and a trend of association of TaqI A1
      allele of DRD2 with alcohol dependence. Haplotype with the predisposing -141C Ins
      and TaqI A1 alleles (-141C Ins-A-A1) seems to confer approximately 2.5 times more
      risk to develop alcohol dependence. CONCLUSIONS: The study provides preliminary
      insight into genetic risk to alcohol dependence in Indian males. Two
      polymorphisms namely, -141C Ins/Del and TaqI A in DRD2 gene may have clinical
      implications among Indian alcoholic subjects.

PMID- 20146829
TI  - Risk scoring systems for adults admitted to the emergency department: a
      systematic review.
AB  - BACKGROUND: Patients referred to a medical admission unit (MAU) represent a broad
      spectrum of disease severity. In the interest of allocating resources to those
      who might potentially benefit most from clinical interventions, several scoring
      systems have been proposed as a triaging tool.Even though most scoring systems
      are not meant to be used on an individual level, they can support the more
      inexperienced doctors and nurses in assessing the risk of deterioration of their
      patients.We therefore performed a systematic review on the level of evidence of
      literature on scoring systems developed or validated in the MAU. We hypothesized
      that existing scoring systems would have a low level of evidence and only few
      systems would have been externally validated. METHODS: We conducted a systematic
      search using Medline, EMBASE and the Cochrane Library, according to the PRISMA
      guidelines, on scoring systems developed to assess medical patients at
      admission.The primary endpoints were in-hospital mortality or transfer to the
      intensive care unit. Studies derived for only a single or few diagnoses were
      excluded.The ability to identify patients at risk (discriminatory power) and
      agreement between observed and predicted outcome (calibration) along with the
      method of derivation and validation (application on a new cohort) were extracted.
      RESULTS: We identified 1,655 articles. Thirty were selected for further review
      and 10 were included in this review.Eight systems used vital signs as variables
      and two relied mostly on blood tests.Nine systems were derived using regression
      analysis and eight included patients admitted to a MAU. Six systems used in
      hospital mortality as their primary endpoint.Discriminatory power was specified
      for eight of the scoring systems and was acceptable or better in five of these.
      The calibration was only specified for four scoring systems. In none of the
      studies impact analysis or inter-observer reliability were analyzed.None of the
      systems reached the highest level of evidence. CONCLUSIONS: None of the 10
      scoring systems presented in this article are perfect and all have their
      weaknesses. More research is needed before the use of scoring systems can be
      fully implemented to the risk assessment of acutely admitted medical patients.

PMID- 20146831
TI  - Motor difficulties in specific language impairment: evidence for the Iverson
      account? - a commentary on Iverson's 'Developing language in a developing body:
      the relationship between motor development and language development'.

PMID- 20146830
TI  - The influence of the Gilgel-Gibe hydroelectric dam in Ethiopia on caregivers'
      knowledge, perceptions and health-seeking behaviour towards childhood malaria.
AB  - BACKGROUND: Malaria remains the most important public health problem in tropical
      and subtropical areas. Mothers' or caregivers' ability to recognize childhood
      malaria-related morbidity is crucial as knowledge, attitudes and health seeking
      behavior of caregivers towards childhood malaria could influence response to
      signs of the disease. METHODS: A total of 1,003 caregivers in 'at-risk' villages
      in close proximity to the Gilgel-Gibe hydroelectric dam in south-western
      Ethiopia, and 953 caregivers in 'control' villages further away from the dam were
      surveyed using structured questionnaires to assess their knowledge, perceptions
      and health seeking behaviour about childhood malaria. RESULTS: Malaria (busa) was
      ranked as the most serious health problem. Caregivers perceived childhood malaria
      as a preventable ('at-risk' 96%, 'control' 86%) and treatable ('at-risk' 98% and
      'control' 96%) disease. Most caregivers correctly associated the typical clinical
      manifestations with malaria attacks. The use of insecticide-treated nets (ITNs)
      was mentioned as a personal protective measure, whereas the role of indoor
      residual spraying (IRS) in malaria prevention and control was under-recognized.
      Most of the caregivers would prefer to seek treatment in health-care services in
      the event of malaria and reported the use of recommended anti-malarials.
      CONCLUSION: Health education to improve knowledge, perceptions and health-seeking
      behaviour related to malaria is equally important for caregivers in 'at risk'
      villages and caregivers in 'control' villages as minimal differences seen between
      both groups. Concluding, there may be a need of more than one generation after
      the introduction of the dam before differences can be noticed. Secondly,
      differences in prevalence between 'control' and 'at-risk' villages may not be
      sufficient to influence knowledge and behaviour.

PMID- 20146832
TI  - A functional MRI study of verbal fluency in adults with bipolar disorder and
      their unaffected relatives.
AB  - BACKGROUND: Individuals with a history of bipolar disorder demonstrate
      abnormalities of executive function, even during euthymia. The neural
      architecture underlying this and its relationship with genetic susceptibility for
      illness remain unclear. METHOD: We assessed 18 remitted individuals with bipolar
      disorder, 19 of their unaffected first degree relatives and 19 healthy controls
      using functional magnetic resonance imaging (fMRI) and a paced verbal fluency
      task with two levels of difficulty. RESULTS: Bipolar patients made significantly
      more errors in the easy level of the verbal fluency task than their relatives or
      controls. Analysis of variance of fMRI data demonstrated a significant main
      effect of group in a large cluster including retrosplenial cortex and adjacent
      precuneate cortex (x=7, y=-56, x=15). All three groups showed deactivation in
      these areas during task performance relative to a neutral or rest condition.
      Group differences comprised a lesser amount of deactivation in unaffected
      relatives compared with controls in the easy condition [F(2, 55)=3.42, p=0.04]
      and in unaffected relatives compared with bipolar patients in the hard condition
      [F(2, 55)=4.34, p=0.018]. Comparison with the control group indicated that both
      bipolar patients and their relatives showed similar deficits of deactivation in
      retrosplenial cortex and reduced activation of left prefrontal cortex.
      CONCLUSIONS: Bipolar disorder may be associated with an inherited abnormality of
      a neural network incorporating left prefrontal cortex and bilateral retrosplenial
      cortex.

PMID- 20146833
TI  - Impact of severity and type of depression on quality of life in cases identified
      in the community.
AB  - BACKGROUND: The impact of different levels of depression severity on quality of
      life (QoL) is not well studied, particularly regarding ICD-10 criteria. The ICD
      classification of depressive episodes in three levels of severity is also
      controversial and the less severe category, mild, has been considered as
      unnecessary and not clearly distinguishable from non-clinical states. The present
      work aimed to test the relationship between depression severity according to ICD
      10 criteria and several dimensions of functioning as assessed by Medical Outcome
      Study (MOS) 36-item Short Form general health survey (SF-36) at the population
      level. METHOD: A sample of 551 participants from the second phase of the Outcome
      of Depression International Network (ODIN) study (228 controls without depression
      and 313 persons fulfilling ICD criteria for depressive episode) was selected for
      a further assessment of several variables, including QoL related to physical and
      mental health as measured with the SF-36. RESULTS: Statistically significant
      differences between controls and the depression group were found in both physical
      and mental markers of health, regardless of the level of depression severity;
      however, there were very few differences in QoL between levels of depression as
      defined by ICD-10. Regardless of the presence of depression, disability, widowed
      status, being a woman and older age were associated with worse QoL in a
      structural equation analysis with covariates. Likewise, there were no differences
      according to the type of depression (single-episode versus recurrent).
      CONCLUSIONS: These results cast doubt on the adequacy of the current ICD
      classification of depression in three levels of severity.

PMID- 20146835
TI  - Spatial and temporal dynamics of potato tuberworm (Lepidoptera: Gelechiidae) in
      the Columbia Basin of the Pacific Northwest.
AB  - A landscape-scale study from 2004 to 2006 investigated the spatial and temporal
      dynamics of a new pest to the Columbia Basin of the Pacific Northwest, the potato
      tuberworm, Phthorimaea operculella (Zeller). Male P. operculella were monitored
      in spring, summer, and fall each year with a pheromone-baited trapping network in
      Oregon and Washington. The objectives of the study were to (1) describe the
      temporal and spatial dynamics of the recent outbreak of P. operculella in the
      region and (2) examine the relationship of the spatial and temporal distribution
      of the outbreak and weather (air temperature, precipitation, and dew point) and
      geographic variables (elevation and latitude). Weather data during the P.
      operculella outbreak were compared with a reference period (1993-1999) that
      occurred before the outbreak. The outbreak in 2004, which caused the first
      widespread tuber damage in the region, was positively associated with warmer
      temperatures in the preceding fall and in the spring, summer, and fall of the
      growing season. October and November 2003 and March 2004 were also drier than the
      reference period. However, the winter of 2003/2004 was colder than the reference
      period and thus mild winter conditions did not explain the outbreak. The
      importance of environmental variables on the seasonal spatial distribution of the
      pest each year was examined using nonparametric multiplicative regression.
      Locations with higher spring, summer, or fall temperatures were associated with
      increased trapping rates in most seasons. Elevation and latitude seemed to play a
      constraining role, because low trapping rates of P. operculella were associated
      with higher elevations and latitudes.

PMID- 20146836
TI  - Temporal patterns in Homalodisca spp. (Hemiptera: Cicadellidae) oviposition on
      southern California citrus and jojoba.
AB  - A detailed study of the distribution of egg masses of Homalodisca vitripennis
      (Germar) and H. liturata Ball was done across a 2-yr period (2001-2003) on six
      host plants in southern California (Marsh grapefruit, Lisbon lemon, Washington
      navel, Dancy tangerine, rough lemon, and jojoba in Riverside; jojoba in Desert
      Center). The majority of egg masses in Riverside belonged to H. vitripennis (84
      100%), whereas in Desert Center, all Homalodisca egg masses were H. liturata.
      Oviposition in Riverside occurred in two discrete periods, a late winter and
      spring period (mid-February to late May), followed by a short interval of very
      low oviposition during most of June, and then a summer period (late June to late
      September) followed by a relatively long period of very low oviposition in fall
      and early winter (October to mid-February). Levels of oviposition during the late
      winter-spring period were similar to those during the summer despite an observed
      larger population of adults during the latter period. Moreover, egg clutch size
      for H. vitripennis was generally greater in spring than during summer and was
      generally higher than that for H. liturata, especially on Riverside jojoba.
      Larger egg clutch size was seen on grapefruit than on lemon, navel, and tangerine
      during summer. There appeared to be temporal host shifts in oviposition; most
      evident was the shift from relatively high rates of oviposition on lemon and
      tangerine in late winter-early spring to relatively higher rates of oviposition
      on grapefruit and navel during summer.

PMID- 20146834
TI  - Functioning and disability levels in primary care out-patients with one or more
      anxiety disorders.
AB  - BACKGROUND: Anxiety disorders are the most prevalent mental health disorders and
      are associated with substantial disability and reduced well-being. It is unknown
      whether the relative impact of different anxiety disorders is due to the anxiety
      disorder itself or to the co-occurrence with other anxiety disorders. This study
      compared the functional impact of combinations of anxiety disorders in primary
      care out-patients. METHOD: A total of 1004 patients with panic disorder (PD),
      generalized anxiety disorder (GAD), social anxiety disorder (SAD) or post
      traumatic stress disorder (PTSD) provided data on their mental and physical
      functioning, and disability. Multivariate regressions compared functional levels
      for patients with different numbers and combinations of disorders. RESULTS: Of
      the patients, 42% had one anxiety disorder only, 38% two, 16% three and 3% all
      four. There were few relative differences in functioning among patients with only
      one anxiety disorder, although those with SAD were most restricted in their work,
      social and home activities and those with GAD were the least impaired.
      Functioning levels tended to deteriorate as co-morbidity increased. CONCLUSIONS:
      Of the four anxiety disorders examined, GAD appears to be the least disabling,
      although they all have more in common than in distinction when it comes to
      functional impairment. A focus on unique effects of specific anxiety disorders is
      inadequate, as it fails to address the more pervasive impairment associated with
      multiple anxiety disorders, which is the modal presentation in primary care.

PMID- 20146837
TI  - Relationship of soybean aphid (Hemiptera: Aphididae) to soybean plant nutrients,
      landscape structure, and natural enemies.
AB  - In the north central United States, populations of the exotic soybean aphid,
      Aphis glycines Matsumura (Hemiptera: Aphididae), are highly variable across
      space, complicating effective aphid management. In this study we examined
      relationships of plant nutrients, landscape structure, and natural enemies with
      soybean aphid abundance across Iowa, Michigan, Minnesota, and Wisconsin,
      representing the range of conditions where soybean aphid outbreaks have occurred
      since its introduction. We sampled soybean aphid and its natural enemies,
      quantified vegetation land cover and measured soybean nutrients (potassium [K]
      and nitrogen [N]) in 26 soybean sites in 2005 and 2006. Multiple regression
      models found that aphid abundance was negatively associated with leaf K content
      in 2005, whereas it was negatively associated with habitat diversity (Simpson's
      index) and positively associated with leaf N content in 2006. These variables
      accounted for 25 and 27% of aphid variability in 2005 and 2006, respectively,
      suggesting that other sources of variability are also important. In addition, K
      content of soybean plants decreased with increasing prevalence of corn-soybean
      cropland in 2005, suggesting that landscapes that have a high intensification of
      agriculture (as indexed by increasing corn and soybean) are more likely to have
      higher aphid numbers. Soybean aphid natural enemies, 26 species of predators and
      parasitoids, was positively related to aphid abundance; however, enemy-to-aphid
      abundance ratios were inversely related to aphid density, suggesting that soybean
      aphids are able to escape control by resident natural enemies. Overall, soybean
      aphid abundance was most associated with soybean leaf chemistry and landscape
      heterogeneity. Agronomic options that can ameliorate K deficiency and maintaining
      heterogeneity in the landscape may reduce aphid risk.

PMID- 20146838
TI  - Deriving the species richness distribution of Geotrupinae (Coleoptera:
      Scarabaeoidea) in Mexico from the overlap of individual model predictions.
AB  - Predictions from individual distribution models for Mexican Geotrupinae species
      were overlaid to obtain a total species richness map for this group. A database
      (GEOMEX) that compiles available information from the literature and from several
      entomological collections was used. A Maximum Entropy method (MaxEnt) was applied
      to estimate the distribution of each species, taking into account 19 climatic
      variables as predictors. For each species, suitability values ranging from 0 to
      100 were calculated for each grid cell on the map, and 21 different thresholds
      were used to convert these continuous suitability values into binary ones
      (presence-absence). By summing all of the individual binary maps, we generated a
      species richness prediction for each of the considered thresholds. The number of
      species and faunal composition thus predicted for each Mexican state were
      subsequently compared with those observed in a preselected set of well-surveyed
      states. Our results indicate that the sum of individual predictions tends to
      overestimate species richness but that the selection of an appropriate threshold
      can reduce this bias. Even under the most optimistic prediction threshold, the
      mean species richness error is 61% of the observed species richness, with
      commission errors being significantly more common than omission errors (71 +/- 29
      versus 18 +/- 10%). The estimated distribution of Geotrupinae species richness in
      Mexico in discussed, although our conclusions are preliminary and contingent on
      the scarce and probably biased available data.

PMID- 20146839
TI  - Modeling distribution and abundance of soybean aphid in soybean fields using
      measurements from the surrounding landscape.
AB  - Soybean aphid (Aphis glycines Matsumura) is a severe pest of soybean in central
      North America. Outbreaks of the aphid in Ontario are often spotty in
      distribution, with some geographical areas affected severely and others with few
      or no aphid populations occurring in soybean for the duration of the season. A.
      glycines spend summers on soybean and overwinter on buckthorn, a shrub that is
      widespread in southern Ontario and is commonly found in agricultural hedgerows
      and at the margins of woodlots. A. glycines likely use both short distance
      migratory flights from buckthorn and longer distance dispersal flights in the
      search for acceptable summer hosts. This study aims to model colonization of
      soybean fields by A. glycines engaged in early-season migration from
      overwintering hosts. Akaike's information criterion (AIC) was used to rank
      numerous competing linear and probit models using field parameters to predict
      aphid presence, colonization, and density. The variable that best modeled aphid
      density in soybean fields in the early season was the ratio of buckthorn density
      to field area, although dramatic differences in relationships between the
      parameters were observed between study years. This study has important
      applications in predicting areas that are at elevated risk of developing
      economically damaging populations of soybean aphid and which may act as sources
      for further infestation.

PMID- 20146840
TI  - Factors affecting stem borer parasitoid species diversity and parasitism in
      cultivated and natural habitats.
AB  - The effects of biotic and abiotic factors on stem borer parasitoid diversity,
      abundance, and parasitism were studied in cultivated and natural habitats in four
      agroecological zones in Kenya. Comparing habitat types, we found partial support
      for the "natural enemy" hypothesis, whereby, across all localities, parasitoid
      diversity was higher in more diverse host plant communities in natural habitats,
      whereas parasitoid abundance was higher in cultivated habitats. For both
      habitats, parasitoid richness was mainly influenced by stem borer density and/or
      its interaction with stem borer richness, whereas parasitoid abundance was mainly
      affected by stem borer abundance. Parasitoid richness was higher in localities
      (with bimodal rainfall distribution) with increased spatial and temporal
      availability of host plants that harbored the borers. Across seasons, parasitoid
      richness was lower in both cultivated and natural habitats in the driest
      locality, Mtito Andei. Overall, parasitoid diversity was low in Suam and Mtito
      Andei, where maize cultivation was practiced on a commercial scale and intense
      grazing activities persist across seasons, respectively. Across localities,
      habitats, and seasons, stem borer parasitism was positively correlated with
      parasitoid richness and abundance. Furthermore, the interaction of rainfall and
      altitude influenced the presence and absence of parasitoids, and consequently,
      stem borer parasitism. Parasitism was positively and negatively correlated with
      temperature in cultivated and natural habitats, respectively. Overall, natural
      habitats seem to serve as important refugia for sustaining parasitoid diversity,
      which in turn can affect stem borer parasitism in the cereal cropping system.

PMID- 20146841
TI  - Phytophagous arthropods of invasive swallow-wort vines (Vincetoxicum spp.) in New
      York.
AB  - Pale swallow-wort (Vincetoxicum rossicum [Kleopow] Barbar.) and black swallow
      wort (V. nigrum [L.] Moench), European species of herbaceous, perennial viny
      milkweeds, have become increasingly invasive in various natural and managed
      habitats in the northeastern United States and southeastern Canada, including low
      and high-light habitats. A classical biological control program is being
      developed, but almost no information was available on the current arthropod fauna
      for either species in the invaded range. I conducted quantitative surveys on pale
      and black swallow-wort at several locations in New York State over 3 yr to
      identify and compare the seasonal assemblage of phytophagous arthropods that are
      feeding and developing on the plants in sunny and shaded habitats. Of the
      approximately 84 nonpredatory species collected, 10 polyphagous, ectophagous
      species of native and exotic arthropods were identified, exclusively from the
      leaves or stems, which could develop to the adult stage and in most cases
      complete at least one generation on one or both species of swallow-wort. However,
      their densities were low throughout the season and generally did not differ
      between the sunny and shaded habitats. Very little to no damage was observed on
      the plants. Exotic swallow-worts seem to have been released from specialized
      natural enemies and have not accrued a damaging suite of generalist herbivores.
      This may be a contributing factor in the increasing invasiveness of these weeds,
      and biological control appears promising for these plants.

PMID- 20146842
TI  - The ladybeetle community (Coleoptera: Coccinellidae) in southern olive
      agroecosystems of Spain.
AB  - The aim of this survey is to faunistically describe ladybeetle assemblages from
      the canopies of olive orchards in southern Spain (Cordoba and Granada) and
      determine the indicator ladybeetle species that are representative of each
      region, taking into account (1) the ecological importance of predatory ladybeetle
      species in olive orchards and (2) the variability of ladybeetle community
      composition in relation to landscape configuration and different farming systems
      (organic, integrated, and conventional), using ordination and classification
      methods. The total number of coccinellids collected was 481; they belonged to 9
      genera and 13 species. Canonical correspondence analysis (CCA) showed a clear
      separation between orchards from Granada and orchards from Cordoba, taking into
      account ladybeetle species, environmental variables, and sampled orchards. The
      land use types and geographical locations showed that Scymnus mediterraneus
      Iablokoff-Khnzorian 1972 and Platynaspis luteorubra (Goeze, 1777) captured at
      higher latitudes benefited more from a larger organic olive area and from the
      presence of holm oak forests in the surrounding area. Coccinella septempunctata
      L., 1758 and Hippodamia variegata (Goeze, 1777) were found at lower latitudes and
      at higher longitudes. Ladybeetle assemblages can vary in response to the type of
      farming system, especially with regard to pesticide use and landscape
      configuration. Nevertheless, evaluation of species composition might help
      identify the state of conservation of these agroecosystems. This knowledge could
      be used to improve the sustainability of agricultural landscapes to increase the
      presence of coccinellids and their ecological function in olive pest control.

PMID- 20146843
TI  - Difference in mosquito species (Diptera: Culicidae) and the transmission of Ross
      River virus between coastline and inland areas in Brisbane, Australia.
AB  - This study examined the distribution of major mosquito species and their roles in
      the transmission of Ross River virus (RRV) infection for coastline and inland
      areas in Brisbane, Australia (27 degrees 28' S, 153 degrees 2' E). We obtained
      data on the monthly counts of RRV cases in Brisbane between November 1998 and
      December 2001 by statistical local areas from the Queensland Department of Health
      and the monthly mosquito abundance from the Brisbane City Council. Correlation
      analysis was used to assess the pairwise relationships between mosquito density
      and the incidence of RRV disease. This study showed that the mosquito abundance
      of Aedes vigilax (Skuse), Culex annulirostris (Skuse), and Aedes vittiger (Skuse)
      were significantly associated with the monthly incidence of RRV in the coastline
      area, whereas Aedes vigilax, Culex annulirostris, and Aedes notoscriptus (Skuse)
      were significantly associated with the monthly incidence of RRV in the inland
      area. The results of the classification and regression tree (CART) analysis show
      that both occurrence and incidence of RRV were influenced by interactions between
      species in both coastal and inland regions. We found that there was an 89% chance
      for an occurrence of RRV if the abundance of Ae. vigilax was between 64 and 90 in
      the coastline region. There was an 80% chance for an occurrence of RRV if the
      density of Cx. annulirostris was between 53 and 74 in the inland area. The
      results of this study may have applications as a decision support tool in
      planning disease control of RRV and other mosquito-borne diseases.

PMID- 20146844
TI  - Impact of five commercial baits containing chitin synthesis inhibitors on the
      protist community in Reticulitermes flavipes (Isoptera: Rhinotermitidae).
AB  - Eastern subterranean termite, Reticulitermes flavipes (Kollar), workers were
      continuously exposed to one of five chitin synthesis inhibiting (CSI) active
      ingredients and the protist community from the hindgut quantified biweekly for 21
      d. The CSIs tested included commercially available formulations of diflubenzuron,
      hexaflumuron, lufenuron, noviflumuron, and novaluron. Results showed termites
      exposed to CSIs had a significant decrease (>or=30%) in the estimated total
      protist population after 3 d, regardless of treatment. Protist species impacted
      were Dinenympha fimbriata, D. gracilis, Microjoenia fallax, Pyrsonympha vertens,
      and Trichonympha agilis and could be indicative of weakened digestive
      homeostasis, but further studies are needed. We also provide evidence that
      lufenuron is highly toxic and discuss some of the implications this might have on
      termite management practices.

PMID- 20146845
TI  - Presence of multiparasite infections within individual colonies of leaf-cutter
      ants.
AB  - Host-parasite dynamics can be altered when a host is infected by multiple
      parasite genotypes. The different strains of parasite are expected to compete for
      the limited host resources, potentially affecting the survival and reproduction
      of the host as well as the infecting parasites. Fungus-growing ants, including
      the well-known leaf-cutters, are an emerging model system for studying the
      evolution and ecology of symbiosis and host-parasite dynamics. We examine whether
      the fungus gardens of leaf-cutter ants can be simultaneously infected by multiple
      strains of the fungal pathogen Escovopsis. Intensive sampling of Escovopsis was
      conducted from individual gardens, as well as between different garden chambers
      within individual colonies of leaf-cutting ants. Isolates obtained were genotyped
      by DNA sequencing. We found that, minimally, 67% of the individual colonies of
      the leaf-cutter ant genera Atta and Acromyrmex and 50% of the At. colombica
      garden chambers studied were simultaneously infected by multiple distinct
      Escovopsis strains. Experimental challenges showed that different Escovopsis
      strains do not exhibit obvious antagonism toward each other, suggesting that
      coinfecting strains of the parasite do not engage in interference competition,
      although interactions were not studied at the cellular level. Further research is
      needed to understand interparasite interactions between coinfecting Escovopsis
      strains and to understand the impact of multiparasite infections on the survival
      of leaf-cutter ant gardens.

PMID- 20146846
TI  - Life history of Parafreutreta regalis (Diptera: Tephritidae): a candidate agent
      for biological control of Delairea odorata.
AB  - Cape-ivy, Delairea odorata Lamaire, is an ornamental vine, native to the eastern
      part of South Africa, which has escaped into natural areas in many countries and
      become a serious pest. Exploratory surveys in South Africa located several
      potential biological control agents. One of these is Parafreutreta regalis Munro,
      a tephritid fly that causes large (14 by 20 mm) galls to form on the stems of
      Cape-ivy. Female P. regalis oviposit 1-20 eggs into stem nodes or growing tips of
      Cape-ivy. During her lifetime, a female may oviposit up to 138 eggs (mean = 61.5
      eggs). After 2 wk, the first swellings, indicating gall formation, become
      visible. There are three larval stages, and, 1 mo after oviposition, the gall is
      fully formed, and the larvae within scrape a small circular hole through the gall
      wall, leaving a "window" covered by intact plant cuticle. After another month,
      adult flies break the window and emerge from the gall. The life cycle from
      oviposition to adult emergence is approximately 2 mo, and we observed up to seven
      generations in a year in our quarantine laboratory. Females begin ovipositing
      within a day or two of emergence, and adults live for approximately 2 wk. We
      compare the life history of P. regalis to the published information about other
      Parafreutreta species.

PMID- 20146847
TI  - Effects of larval host plant species on fecundity of the generalist insect
      herbivore Ennomos subsignarius (Lepidoptera: Geometridae).
AB  - The elm spanworm, Ennomos subsignarius Hubner (Lepidoptera: Geometridae), is an
      eruptive herbivore that feeds on numerous tree species in forests throughout its
      range. An unprecedented outbreak in an urban environment in St. John's,
      Newfoundland, Canada, caused severe levels of defoliation to a number of native
      and exotic hardwood tree species, some of which represent novel hosts for this
      insect. Increased insect performance on these novels hosts was hypothesized as
      having contributed to the outbreak. To assess this, percentage larval survival
      and pupal weight were measured for larvae reared on foliage from six different
      tree species in a no-choice laboratory bioassay. Adult longevity and fecundity
      (no. eggs laid per female) were assessed for laboratory-reared individuals, as
      well as for pupae collected from eight different host tree species from the
      field. A survey to assess feeding occurrence measured defoliation on eight tree
      species. During this urban outbreak, sycamore maple, Acer pseudoplatanus, a tree
      species not native to North America, experienced the highest levels of
      defoliation. Performance of E. subsignarius (pupal weight, female longevity, and
      fecundity) on this host was comparable with the known host of elm (Ulmus spp.).
      Despite the fact that E. subsignaria performed well on several introduced hosts,
      fecundity levels were much lower than previously published reports, suggesting
      that the current outbreak is not caused by increased fecundity on these novel
      hosts in contrast to the hypothesis.

PMID- 20146848
TI  - Spatial patterns of grass seedling recruitment imply predation and facilitation
      by harvester ants.
AB  - Extended drought on the Edwards Plateau, TX, causes high mortality in grass
      species' populations and their replacement by recruitment from the seeds of
      survivors. Harvester ant nests may act as refugia for perennial plants during
      drought, as evidenced by a high survivorship of plants directly adjacent to
      nests. Because grasses tend to disperse seeds short distances and drought
      eliminated seed banks, we hypothesized that the spatial pattern of grass
      seedlings and adults would be clumped at small scales around these refugia. In
      contrast, nests would be regular at small to moderate scales. We studied the
      spatial patterns of seedlings, adults, and ant nest locations using a modified
      Ripley's K-function technique for transect data. Point data were collected along
      a 1-km transect. Spatially regular patterns were found for nests from 1.0- to
      22.0-m scales. We found that two species' seedlings and adults were significantly
      clumped with ant nests, and two species had significantly regular spatial
      patterns with nests. Surprisingly, patterns of clumped seedlings occurred up to
      30-m scales with nests. Nests appear to affect seedling establishment at multiple
      scales. These results suggest that nests may facilitate colonization for some
      grass populations, but regular spatial patterns in other species imply that
      forager seed harvest may inhibit establishment.

PMID- 20146849
TI  - Factors affecting appearance of stink bug (Hemiptera: Pentatomidae) injury on
      apple.
AB  - Three main types of stink bug injury have been reported on the surface of apple
      fruit: (1) discolored dots, (2) discolored dots with depressions, and (3)
      discolored dots with discolored depressions. From 2005 to 2008, studies were
      performed to determine the factors linked to the variations in the appearance of
      adult stink bug injury on apple fruit observed at harvest. The main factors
      tested were type of feeding injury (i.e., mechanical versus breakdown and removal
      of tissues), time between injury and evaluation, cultivar, fruit maturity, and
      relative exposure to sunlight and UV radiation. No differences were observed that
      were caused by type of feeding. Studies of the time between injury and evaluation
      showed that there is a progression in the development of injury appearance. This
      progression of injury is influenced by cultivar and relative maturity of the
      fruit. Concomitantly, sites of injury on fruit exposed to no or limited sunlight
      and UV radiation were less likely to progress to discolored depressions.

PMID- 20146850
TI  - Floral transmission of Erwinia tracheiphila by cucumber beetles in a wild
      Cucurbita pepo.
AB  - Cucumber beetles, Acalymma vittatum (F.) and Diabrotica undecipunctata howardi
      (Barber), are specialist herbivores of cucurbits and the vector of Erwinia
      tracheiphila (E.F. Smith) Holland, the causative agent of wilt disease. Cucumber
      beetles transmit E. tracheiphila when infected frass falls onto leaf wounds at
      the site of beetle feeding. We show that E. tracheiphila also can be transmitted
      via the floral nectaries of Cucurbita pepo ssp. texana L. Andres (Texas gourd).
      Under field conditions, we found that beetles aggregate in flowers in the late
      morning, that these beetles chew the anther filaments that cover the nectaries in
      male flowers thereby exposing the nectary, and that beetle frass accumulates on
      the nectary. We use real-time polymerase chain reaction to show that most of the
      flowers produced during the late summer possess beetle frass containing E.
      tracheiphila. Greenhouse experiments, in which cultures of E. tracheiphila are
      deposited onto floral nectaries, show that Texas gourds can contract wilt disease
      through the floral nectaries. Finally, we use green fluorescent protein
      transformed E. tracheiphila to document the movement of E. tracheiphila through
      the nectary into the xylem of the pedicel before the abscission of the flower.
      Together, these data show that E. tracheiphila can be transmitted through
      infected frass that falls on or near the floral nectaries. We hypothesize that
      the concentration of frass from many beetles in the flowers increases both
      exposure to and the concentration of E. tracheiphila and plays a major role in
      the dynamics of wilt disease in both wild populations and cultivated squash
      fields.

PMID- 20146851
TI  - Nest establishment, pollination efficiency, and reproductive success of Megachile
      rotundata (Hymenoptera: Megachilidae) in relation to resource availability in
      field enclosures.
AB  - The alfalfa leafcutting bee, Megachile rotundata (Fabricius), is used to
      pollinate alfalfa, Medicago sativa L., for seed production in the United States
      and Canada. It is difficult to reliably sustain commercial M. rotundata
      populations in the United States because of problems with disease, parasites,
      predators, and unexplained mortality. One possible explanation for early immature
      mortality is that, relative to floral availability, superfluous numbers of bees
      are released in alfalfa fields where resources quickly become limited. Our
      objective was to determine how M. rotundata density affects bee nesting,
      pollination efficiency, and reproductive success. Various numbers of bees were
      released into enclosures on an alfalfa field, but only 10-90% of released female
      bees established nests. Therefore, a "bee density index" was derived for each
      enclosure from the number of established females and number of open flowers over
      time. As the density index increased, significant reductions occurred in the
      number of pollinated flowers, number of nests, and number of cells produced per
      bee, as well as the percentage of cells that produced viable prepupae by summer's
      end and the percentage that produced adult bees. The percentage of cells
      resulting in early brood mortality (i.e., pollen balls) significantly increased
      as the density index increased. We conclude that bee nest establishment,
      pollination efficiency, and reproductive success are compromised when bee
      densities are high relative to floral resource availability. Open field studies
      are needed to determine commercial bee densities that result in sustainable bee
      populations and adequate pollination for profitable alfalfa seed production.

PMID- 20146852
TI  - Potential host plants of Trirhabda geminata (Coleoptera: Chrysomelidae): impacts
      on survival, development, and feeding.
AB  - Although larvae and adults of the herbivorous beetle Trirhabda geminata Horn
      (Coleoptera: Chrysomelidae) are primarily considered to be specialists on Encelia
      farinosa (Compositae: Asteraceae), some reports exist of these beetles feeding on
      related Encelia species. Within the genus Encelia, many species are thought to
      have evolved relatively recently. In addition, some Encelia species have very
      similar secondary chemistries and overlapping geographic distributions. In the
      laboratory, individual T. geminata were reared on E. farinosa or the
      sympatrically occurring species E. actoni or E. californica. Survival, growth,
      and development were analyzed for larvae feeding on each host plant species.
      Overall, herbivore performance was better on E. farinosa, with significantly
      greater survival, faster development, and greater mass gain. Beetle development
      on E. californica was intermediate, with some measure, indicating better
      performance than on E. actoni and other measure, indicating no difference between
      these potential hosts. Importantly, although performance was decreased on E.
      actoni and E. californica, some individuals were able to develop successfully,
      suggesting that populations of T. geminata may be able to adapt to use these host
      plants.

PMID- 20146853
TI  - Compatibility of seed head biological control agents and mowing for management of
      spotted knapweed.
AB  - Field studies were conducted at two sites in western Montana during 2006 and 2008
      to assess the compatibility of mowing with five seed head insect species
      introduced for biological control of spotted knapweed, Centaurea stoebe Lamarck
      subsp. micranthos. In 2006, mowing of spotted knapweed plants at the bolting and
      flower bud stages resulted in the development of new seed heads that contained
      significantly more seeds and significantly fewer larvae of each insect species
      than in seed heads in unmowed controls. No seed heads were produced in the plots
      mowed at the flowering stage. Seed numbers per seed head in 2008 were also
      significantly higher in plots mowed at the bolting stage than in unmowed
      controls, but between-treatment differences in insect numbers were more variable.
      The seed head insects Larinus spp. and Urophora affinis Frauenfeld were the
      primary cause of the reduced knapweed seed numbers per seed head in 2006. Spotted
      knapweed should not be mowed at the bolting and flower bud stages if large
      populations of seed head insects are present because mowing can result in the
      formation of new seed heads that are free from the insects' attack, thus allowing
      greater seed production. Mowing of spotted knapweed at the flowering stage and
      later can be conducted without a subsequent increase in seed production, but the
      mowing may cause mortality of the insect larvae.

PMID- 20146855
TI  - Preimaginal development response to constant temperatures in Hypera postica
      (Coleoptera: Curculionidae): picking the best model.
AB  - Immature survival and development of alfalfa weevil, Hypera postica (Gyllenhal)
      (Coleoptera: Curculionidae), were examined at 15 constant temperatures ranging
      from 9 to 37 degrees C. At 9 and 37 degrees C, eggs did not develop. Embryos
      developed to adulthood between 11.5 and 36 degrees C, although survival was low
      at both ends of the temperature range. Distribution of development times for all
      stages of alfalfa weevil were skewed toward longer times mainly at moderate
      temperatures. Constant proportion of time spent in egg, larva, and pupa indicated
      rate isomorphy within the range 14-31.5 degrees C. No significant difference was
      shown between development time of males and females at any of the temperatures
      tested. Two linear and 23 nonlinear models were fitted to describe development
      rate of immature stages of H. postica as a function of temperature, as well as
      estimating the thermal constant and critical temperatures (i.e., T(min), T(opt),
      and T(max)). There was no statistical difference between the estimated
      parameters, using Ikemoto and ordinary linear methods. Of the nonlinear models
      fitted, the Logan-6/Lactin-2, Analytis-3/Briere-2, and Analytis-3/Briere-2 models
      were found to be the best for modeling development rate of egg, larva, and entire
      immature stages of H. postica, respectively. Our findings will be incorporated in
      more efficient phenological models of this pest and its population dynamics.

PMID- 20146854
TI  - Evaluating the use of male-produced pheromone components and plant volatiles in
      two trap designs to monitor Anoplophora glabripennis.
AB  - Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae), commonly known
      as the Asian longhorned beetle, is a wood-boring invasive species introduced from
      Asia to North America and Europe in solid wood packing material. Efficient
      monitoring traps are needed to assess population density and dispersal in the
      field and to detect new introductions at ports of entry. For this purpose, we
      conducted field trapping experiments in China in the summers of 2007 and 2008. In
      2007, we tested Intercept panel traps hung on poplar trees. In 2008, we used
      Intercept panel traps hung on poplar trees, screen sleeve traps wrapped around
      poplar trunks, and Intercept panel traps hung on bamboo poles 20 m away from host
      trees. Traps were baited with A. glabripennis male-produced pheromone alone or in
      different combinations with plant volatiles. Traps baited with the male-produced
      pheromone alone caught significantly more females than control traps in both
      years. The addition of a mixture of (-)-linalool, (Z)-3-hexen-1-ol, linalool
      oxide, trans-caryophyllene, and trans-pinocarveol to the pheromone significantly
      increased trap catches of females, 85% of which were virgin. Screen sleeve traps
      baited with a combination of (-)-linalool and the pheromone caught the highest
      number of beetles overall in 2008, whereas traps placed on bamboo polls caught
      the lowest number. Although the logistics for the most effective implementation
      of a trapping program using a mixture of the pheromone and plant volatiles
      require additional studies, these results indicate that this pheromone has
      considerable promise as a monitoring tool for A. glabripennis in the field.

PMID- 20146856
TI  - Effects of forced egg retention on the temporal progression of West Nile virus
      infection in Culex pipiens quinquefasciatus (Diptera: Culicidae).
AB  - Environmental factors that impact the biology of mosquito vectors can have
      epidemiological implications. Lack of oviposition sites facilitated by
      environmental factors such as temperature and drought can often force Culex spp.
      mosquitoes to retain their eggs. Culex pipiens quinquefasciatus Say were fed
      blood meals containing West Nile virus (WNV; family Flaviviridae, genus
      Flavivirus) and either allowed to oviposit or forced to retain their eggs through
      different time points postinfection (9, 13, 20, 27 d) at 28 degrees C.
      Oviposition status did not significantly affect rates of WNV infection (% with
      virus-positive bodies), dissemination (% with virus-positive legs), or
      transmission (% with virus-positive saliva) for any of the tested time points. As
      expected, WNV titers in bodies and legs were significantly (P < 0.05) higher at
      late time points compared with early time points. No significant differences were
      observed in WNV titers in saliva between time points. There were no significant
      effects of oviposition status on virus titers of bodies, legs, or saliva.
      However, we found that egg retention may increase vector competence at early and
      late time points after infection and that a single oviposition event may decrease
      vector competence, possibly by activating an immune response against the virus.
      Environmental changes that influence mosquito biology are important determinants
      of virus transmission, and further studies are needed to assess the effects of
      drought on virus transmission risk and how these interactions affect our
      interpretation of field data.

PMID- 20146857
TI  - Reproductive activity and survivorship of Liriomyza sativae (Diptera:
      Agromyzidae) at different temperatures and relative humidity levels.
AB  - We studied a population of Liriomyza sativae Blanchard (Diptera: Agromyzidae)
      identified by morphological and molecular techniques from the semiarid region of
      the Brazilian northeast. The influence of temperature and relative humidity on
      the survival and reproductive parameters of L. sativae in cowpeas (Vigna
      unguiculata L. Walp.) (Fabales: Fabaceae) was evaluated. We used temperatures of
      18, 20, 22, 25, 28, 30, and 32 +/- 1 degrees C (50 +/- 10% RH) and relative
      humidity values of 30, 50, 70, and 90 +/- 10% (25 +/- 1 degrees C) under a 14
      L:10 D photoperiod. Adult longevity decreased as temperature and relative
      humidity increased and was greater, in general, for females. The preoviposition
      and oviposition periods also decreased as temperature increased, whereas relative
      humidity only caused reductions in the oviposition period at higher levels.
      Fecundity was similar in the range from 18 to 30 degrees C but decreased at 32
      degrees C with respect to relative humidity; the best performances of L. sativae
      occurred at lower levels. The pattern of oviposition rate changed with
      temperature and relative humidity. Regardless of temperature and relative
      humidity, L. sativae laid between 75 and 92% of its eggs on the adaxial surface
      of the cowpea leaves. This information will be highly useful to design a
      leafminer production system aimed at the multiplication of natural enemies, as
      well as for pest management in the field.

PMID- 20146858
TI  - Degree-day requirements for alfalfa weevil (Coleoptera: Curculionidae)
      development in eastern Nebraska.
AB  - The alfalfa weevil, Hypera postica (Gyllenhal), is a serious, yet sporadic
      defoliator of alfalfa, Medicago sativa L., in Nebraska. A 2-yr study was
      conducted in 2005 and 2006 to test for variation in degree-day requirements by
      location in eastern Nebraska. Sampling took place along a latitudinal gradient in
      three regions of eastern Nebraska. Three fields were sampled in each region
      during the 2 yr of the study. Alfalfa weevil larval degree-day requirements were
      found to vary by latitude in eastern Nebraska. Alfalfa weevil larvae were
      discovered in southern regions after fewer developmental degree-days had
      accumulated than in fields in the northern regions. Alfalfa weevils may be more
      damaging to alfalfa in southern regions than in northern regions of eastern
      Nebraska because they emerge earlier relative to alfalfa growth. Management
      implications of this shift in alfalfa weevil phenology are discussed.

PMID- 20146859
TI  - Morphological deformities in Chironomus spp. (Diptera: Chironomidae) larvae as a
      tool for impact assessment of anthropogenic and environmental stresses on three
      rivers in the Juru river system, Penang, Malaysia.
AB  - Morphological deformities in parts of the head capsule of Chironomus spp. larvae
      inhabiting three polluted rivers (Permatang Rawa [PRR], Pasir [PR], and Kilang
      Ubi [KUR]) in the Juru River Basin, northeastern peninsular Malaysia, were
      studied. Samples of the fourth-instar larvae at one location in each river were
      collected monthly from November 2007 to March 2008 and examined for deformities
      of the mentum, antenna, mandible, and epipharyngis. At each sample location, in
      situ measurements of water depth, river width, water pH, dissolved oxygen, and
      water temperature were made. Samples of river water and benthic sediments were
      also collected monthly from each larval sample location in each river and taken
      to the laboratory for appropriate analysis. Total suspended solids (TSSs),
      ammonium-N, nitrate-N, phosphate-P, chloride, sulfate, and aluminum content in
      water were analyzed. Total organic matter and nonresidual metals in the sediment
      samples were also analyzed. Among the three rivers, the highest mean deformity
      (47.17%) was recorded in larvae collected from KUR that received industrial
      discharges from surrounding garment and rubber factories, followed by PRR
      (33.71%) receiving primarily residues of fertilizers and pesticides from adjacent
      rice fields, and PR (30.34%) contaminated primarily by anthropogenic wastes from
      the surrounding residential areas. Among the various head capsule structures,
      deformity of the mentum was strongly reflective of environmental stress and
      amounted to 27.9, 20.87, and 30.19% in the PRR, PR, and KUR, respectively.
      Calculated Lenat's toxic score index satisfactorily explained the influence of
      prevailing environmental variables on the severity of mentum deformities.
      Redundancy analysis and forward selection selected TSSs, sediment Zn, Mn, Cu, and
      Ni, and water pH, dissolved oxygen, water temperature, total organic matter,
      nitrate-N, chloride, phosphate-P, ammonium-N, sulfate, and aluminum as parameters
      that significantly affected some proportion of deformities. The total deformities
      correlated closely with deformities of mentum but only weakly with deformities in
      other parts of head. The total deformity incidence was strongly correlated with
      high contents of sediment Mn and Ni. The mentum and epipharyngis deformities
      incidence was highly correlated with an increase of TSSs, total aluminum, and
      ammonium-N and a decrease in pH and dissolved oxygen.

PMID- 20146860
TI  - Salivary proteins of Russian wheat aphid (Hemiptera: Aphididae).
AB  - Salivary secretions play critical roles in aphid-host plant interactions and are
      responsible for damage associated with aphid feeding. The objectives of this
      study were to evaluate aspects of salivation and the salivary constituents of
      Diuraphis noxia (Hemiptera: Aphididae). Salivary proteins were isolated and
      compared from three aphid probed diets: pure water, 15% sucrose, or amino acids
      (100 mM serine, 100 mM methionine, 100 mM aspartic acid, and 15% sucrose). After
      6 h, more aphids settled on sucrose diet compared with other diets, but there
      were no significant differences in the number of stylet sheaths produced per
      aphid after 24 h. There were differences in the amount of soluble salivary
      protein (watery saliva), with the greatest amount secreted in sucrose diet,
      followed by amino acid diet and pure water, respectively. Protein constituents
      secreted into sucrose and amino acid diets were compared using gel
      electrophoresis using standardized amounts of protein. More protein bands and
      bands of greater intensity were visualized from probed sucrose diet compared with
      probed amino acid diet, indicating qualitative differences. Phosphatase was
      putatively identified from D. noxia saliva from a major protein band using gel
      electrophoresis and mass spectrophotometry. Alkaline phosphatase activity was
      confirmed in sucrose diet using enzymatic assays but was not detected in aphid
      probed water or amino acid diets. Other peptides in sucrose diet weakly but
      significantly showed similarities to putative dehydrogenase and RNA helicase
      expressed sequence tags identified from other aphids. The implications of these
      findings in aphid salivation and plant-insect interactions are discussed.

PMID- 20146861
TI  - Beet webworm (Lepidoptera: Pyralidae) migration in China: evidence from genetic
      markers.
AB  - Genetic diversity within and among 11 geographic populations of the beet webworm
      Loxostege sticticalis across five provinces in the northern part of China were
      evaluated using amplified fragment length polymorphism (AFLP) analysis. Five AFLP
      primer combinations were used on 88 L. sticticalis samples from different
      locations, detecting a total of 384 polymorphic and 27 monomorphic fragments.
      Although extensive genetic diversity occurs among individuals from different
      geographic populations (P = 93.4%, h = 0.398, I = 0.572), the majority of the
      genetic diversity is within populations and not between populations (G(ST) =
      0.196), which agrees well with the results of analysis of molecular variance (84%
      of the total genetic variation is within populations), indicating high gene flow
      (N(M) = 2.046) among natural populations, which are not genetically
      differentiated. L. sticticalis in northeastern China, northern China, and
      northwestern China are part of a single large metapopulation. Cluster analyses
      based on AFLP data were preformed to graphically show groupings between
      individuals and between populations. Individuals from the same region were not
      grouped together very well. Eleven subpopulations were clustered into six broad
      groups, and there was no significant correlation between geographic distance and
      genetic dissimilarity (r = 0.1236, P = 0.8512). Principle component analysis also
      indicated a lack of genetic differentiation between the 11 populations. These
      results indicated that, although high genetic variability existed among
      individuals, there was little genetic differentiation among geographic
      populations, which can be explained by the effects of long distance migration of
      the beet webworm in China and consequent gene flow.

PMID- 20146862
TI  - Effects of transgenic rice expressing Bacillus thuringiensis Cry1Ab protein on
      ground-dwelling collembolan community in postharvest seasons.
AB  - During 2005-2008, field studies were conducted at two locations in Chongqing,
      China, to assess the potential effects of transgenic rice expressing Bacillus
      thuringiensis (Bt) Cry1Ab protein on the nontarget ground-dwelling collembolan
      community in three postharvest seasons. Collembolans in non-Bt and Bt rice fields
      were sampled with pitfall traps during each of two postharvest seasons of
      2005/2006 and 2006/2007 and litterbag traps during each of three postharvest
      seasons of 2005/2006, 2006/2007, and 2007/2008. Ground-dwelling collembolans in
      rice fields during the postharvest seasons were abundant, whereas community
      densities varied considerably between the two locations and among the three
      seasons. A total of 67,310 collembolans, representing three species, Entomobrya
      griseoolivata, Hypogastrura matura, and Bourletiella christianseni, were captured
      during the three postharvest seasons. E. griseoolivata was the predominant
      species, accounting for 87.7% of the total captures, followed by H. matura
      (10.7%) and B. christianseni (1.6%). In general, there were no significant
      differences in species compositions and abundances of each species between Bt and
      non-Bt paddy fields, suggesting no significantly impact of plant residues of
      Cry1Ab rice on collembolan communities during postharvest seasons.

PMID- 20146863
TI  - Visfatin: a potential therapeutic target for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is usually a chronic, systemic inflammatory disorder
      primarily targeting the synovium and articular cartilage. It is incurable, costly
      and responds poorly to treatment. Methotrexate alone or in combination with
      conventional and/or biological disease-modifying antirheumatic drugs (DMARDs) is
      often used to induce remission of active disease. The effectiveness of treatment
      is, however, limited and most patients develop chronic disability and require
      total knee arthroplasty or total hip replacement. Emerging therapies targeting
      specific cytokines and growth factors in the RA inflammatory cascade offer potent
      new means of modifying disease activity. Recently, increased concentrations of
      adipokines, including visfatin, mainly produced by adipocytes in serum and joint
      synovial fluid, were found in RA patients. Visfatin has important pro
      inflammatory and catabolic roles in RA pathogenesis and is now being studied as a
      potential therapeutic target for RA. Here we discuss the relationship between
      visfatin and RA and its potential as a therapeutic target for RA.

PMID- 20146864
TI  - Telmisartan: a different angiotensin II receptor blocker protecting a different
      population?
AB  - The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint
      Trial (ONTARGET()) showed that the angiotensin II receptor blocker (ARB)
      telmisartan was as protective as the reference-standard ramipril in a broad cross
      section of patients at increased cardiovascular risk, but was better tolerated.
      Telmisartan has a unique profile among ARBs, with a high affinity for the
      angiotensin II type 1 receptor, a long duration of receptor binding, a high
      lipophilicity and a long plasma half life. This leads to sustained and powerful
      blood pressure lowering when compared with the first marketed ARBs, such as
      losartan and valsartan. Some pharmacological properties of telmisartan clearly
      distinguish it from other members of the ARB class and may contribute to the
      clinical effects seen with telmisartan. A class effect for ARBs cannot be
      assumed. To date, telmisartan is the only ARB that has been shown to reduce
      cardiovascular risk in at-risk cardiovascular patients.

PMID- 20146865
TI  - Machine learning methods applied to pharmacokinetic modelling of remifentanil in
      healthy volunteers: a multi-method comparison.
AB  - This study compared the blood concentrations of remifentanil obtained in a
      previous clinical investigation with the predicted remifentanil concentrations
      produced by different pharmacokinetic models: a non-linear mixed effects model
      created by the software NONMEM; an artificial neural network (ANN) model; a
      support vector machine (SVM) model; and multi-method ensembles. The ensemble
      created from the mean of the ANN and the non-linear mixed effects model
      predictions achieved the smallest error and the highest correlation coefficient.
      The SVM model produced the highest error and the lowest correlation coefficient.
      Paired t-tests indicated that there was insufficient evidence that the predicted
      values of the ANN, SVM and two multi-method ensembles differed from the actual
      measured values at alpha = 0.05. The ensemble method combining the ANN and non
      linear mixed effects model predictions outperformed either method alone. These
      results indicated a potential advantage of ensembles in improving the accuracy
      and reducing the variance of pharmacokinetic models.

PMID- 20146866
TI  - Accelerometry for evaluation of gait pattern in healthy soccer athletes.
AB  - An accelerometer system was used to measure the characteristics of the motion of
      133 healthy male soccer athletes in a 30-s walking test and the data obtained
      were analysed using the gait evaluation differential entropy method (GEDEM).
      GEDEM processes gait acceleration data and calculates an index that provides a
      quantitative evaluation of a subject's gait, at low cost and with negligible
      effect on the subject. The GEDEM index was not significantly correlated with age,
      body weight, body mass index, or the number of years of active training. The
      GEDEM value for the anterior-posterior axis showed a small negative statistically
      significant correlation with height and the vertical axis was moderately and
      statistically significantly positively correlated with the time spent training
      per week. The triaxial accelerometry system described here is easy for subjects
      and testers to use, and enables measurements to be made on the sports field to
      evaluate an athlete's musculoskeletal condition with respect to gait stability.

PMID- 20146867
TI  - Phenylephrine attenuates intra-operative hypothermia during spinal anaesthesia.
AB  - Inadvertent hypothermia is common during spinal anaesthesia. This study was based
      on the hypothesis that phenylephrine might attenuate core hypothermia by
      inhibiting core-to-peripheral redistribution of body heat during spinal
      anaesthesia. In this prospective randomized study, 20 patients who underwent
      elective orthopaedic surgery under spinal anaesthesia were randomly assigned to
      receive either normal saline (control group) or continuously-infused
      phenylephrine 0.5 microg/kg per min (phenylephrine group). Core temperature,
      heart rate (HR) and mean arterial pressure (MAP) were monitored. Mean +/- SE core
      temperature at the end of surgery was significantly higher in the phenylephrine
      treated group compared with the control group (35.9 +/- 0.1 degrees C versus 35.0
      +/- 0.1 degrees C, respectively), although there was no significant difference in
      baseline core temperature (both groups 36.3 +/- 0.1 degrees C). Mean HR and MAP
      were not significantly different between the two groups. In conclusion,
      continuously-infused phenylephrine attenuated core hypothermia during spinal
      anaesthesia without any haemodynamic complications.

PMID- 20146868
TI  - Procalcitonin levels as an early marker in patients with multiple trauma under
      intensive care.
AB  - This prospective study investigated the levels of procalcitonin (PCT) and C
      reactive protein (CRP) in patients with various types and severity of multiple
      trauma, and their relationship to trauma-related complications. Adult multiple
      trauma patients (n = 113) admitted to the intensive care unit (ICU) in the first
      24 h after trauma were included. The Injury Severity Scores (ISS), and PCT and
      CRP levels were measured in the first 24 h (day 1), on day 7 and on the final day
      of their ICU stay. Survival at 30 days was recorded. Mean PCT and CRP levels were
      both significantly higher on day 7 compared with day 1 and the final assessment
      day in patients with an ISS > 20. Levels of PCT were significantly higher in
      cases with sepsis, severe sepsis or septic shock compared with cases who
      developed systemic inflammatory response syndrome (SIRS), however levels of CRP
      were significantly higher only in cases with severe sepsis or septic shock, but
      not in cases with sepsis alone. These data support the view that PCT levels may
      be a better indicator than CRP levels in the early diagnosis of septic
      complications in patients with multiple trauma.

PMID- 20146869
TI  - Distribution of common methylenetetrahydrofolate reductase gene mutations in
      patients with obstructive sleep apnoea.
AB  - Homocysteine levels have been investigated in patients with obstructive sleep
      apnoea syndrome (OSAS), a syndrome associated with a high level of comorbid
      cardiovascular disease (CVD). While significant increases in homocysteine levels
      have been observed in OSAS patients with CVD, no increases have been noted in
      OSAS patients without CVD. This study was designed to investigate the
      methylenetetrahydrofolate reductase (MTHFR) gene, which is essential for
      homocysteine metabolism and has been shown to have a causal role in the
      development of CVD. Eighty subjects, 30 diagnosed with OSAS by polysomnography
      and 50 controls (healthy volunteers with no symptoms of OSAS) were enrolled. Two
      mutations in the MTHFR gene were investigated using polymerase chain reactions
      and restriction fragment length polymorphisms. No significant differences were
      found in mean age, body mass index, homocysteine levels, or MTHFR allele or
      genotype distributions between patient and control groups.

PMID- 20146870
TI  - Association of collagen type I alpha1 (COLIA1) Sp1 polymorphism with osteoporotic
      fracture in Caucasian post-menopausal women: a meta-analysis.
AB  - This study was designed to summarize quantitatively the evidence for a
      relationship between collagen type I alpha1 (COLIA1) Sp1 polymorphism and
      osteoporotic fracture risk in Caucasian post-menopausal women. This meta-analysis
      included 16 studies, which analysed 2294 patients with fractures and 10 285
      controls. The combined results showed that there was a significant difference in
      genotype distribution (SS odds ratio [OR] 0.72; Ss OR 1.18; ss OR 1.97) between
      patients with fractures and controls. When stratifying by the fracture site, it
      was found that: (i) patients with vertebral fractures had a significantly higher
      frequency of the Ss genotype and a lower frequency of the SS genotype than
      controls; and (ii) patients with non-vertebral fractures had a significantly
      higher frequency of the ss genotype and a lower frequency of the SS genotype than
      controls. This meta-analysis suggests that the COLIA1 Sp1 polymorphism may be
      associated with osteoporotic fracture in Caucasian post-menopausal women.

PMID- 20146871
TI  - Efficacy and safety of an intra-operative intra-articular magnesium/ropivacaine
      injection for pain control following total knee arthroplasty.
AB  - Eighty patients with osteoarthritis who underwent unilateral total knee
      arthroplasty were randomly assigned to two groups: the trial group received an
      intra-operative intra-articular injection of magnesium sulphate and ropivacaine,
      and the control group received an injection of normal saline. All patients
      received patient-controlled analgesia with morphine for 48 h post-operatively. It
      was found that an intra-articular injection of magnesium sulphate and ropivacaine
      significantly reduced morphine consumption during the 0 - 24 h post-operative
      period and total 48-h post-operative morphine consumption. Pain scores at rest
      and during motion in the trial group were significantly lower than in the
      controls during the first 24 h post-operatively. The time to be able to perform a
      straight leg raise and to reach a 90 degrees knee flexion was significantly
      shorter in the trial group compared with the controls. This study demonstrated
      that an intra-operative intra-articular magnesium sulphate and ropivacaine
      injection reduced the use of post-operative morphine.

PMID- 20146872
TI  - Changes in lymphocyte subsets in the peripheral blood of patients with active
      pulmonary tuberculosis.
AB  - The aim of this study was to determine the percentage of lymphocyte subsets in
      peripheral blood in patients with active tuberculosis. A total of 21 patients
      with active tuberculosis and 15 healthy volunteers were included in the study. T
      lymphocyte subsets, B-lymphocytes (CD19(+) cells), natural killer (NK) cells and
      cells positive for costimulatory molecules CD28 and CD152 were evaluated using
      flow cytometry. Patients with tuberculosis had a significantly decreased
      percentage of CD3(+) and CD3(+)CD4(+) cells, and a significantly decreased ratio
      of CD3(+)CD4(+) to CD3(+)CD8(+) cells compared with healthy controls. In
      contrast, the percentage of B-cells (CD19(+) cells), CD3(+)CD8(+) cells, CD28(+)
      cells, CD152(+) cells, and subpopulations of CD4(+)CD152(+), CD8(+)CD152(+) and
      CD8(+)CD28(+) T-cells were all significantly increased compared with healthy
      controls. There were no statistically significant differences in the percentages
      of NK cells or CD4(+)CD28(+) cells between patients and controls. These results
      indicate that patients with active tuberculosis have altered lymphocyte
      homeostasis.

PMID- 20146873
TI  - Immunological study of allogeneic mesenchymal stem cells during bone formation.
AB  - Autologous mesenchymal stem cells (MSCs) are limited in their clinical
      application because tissue-engineered bone cannot be pre-fabricated. Allogeneic
      MSCs are readily available but carry the risk of transplant rejection. It is not
      yet clear whether allogeneic MSCs can induce a rejection response during bone
      formation. In this study, two strains of genetically unmatched mini-pigs were
      used as experimental animals to study the immunological changes in MSCs in vitro
      and in vivo when generating bone. Mini-pig MSCs showed low immunogenicity during
      osteogenesis both in vitro and in vivo, indicating that allogeneic MSCs had
      little or no immunogenicity in osteosis. In conclusion, allogeneic MSCs are an
      important source of seed cells for the tissue engineering of bone. This favours
      the clinical application of pre-constructed tissue-engineered bone.

PMID- 20146874
TI  - Comparison of stress hormone response, interleukin-6 and anaesthetic
      characteristics of two anaesthetic techniques: volatile induction and maintenance
      of anaesthesia using sevoflurane versus total intravenous anaesthesia using
      propofol and remifentanil.
AB  - This prospective randomized study compared the effects of two types of
      anaesthesia on peri-operative anaesthetic profiles from induction to recovery and
      on immunological and neurohormonal responses to anaesthesia and surgical stress.
      Forty patients were assigned to undergo either volatile induction and maintenance
      of anaesthesia (VIMA) with sevoflurane or total intravenous anaesthesia (TIVA)
      with propofol and remifentanil. Plasma adrenaline, noradrenaline, cortisol,
      glucose and interleukin-6 (IL-6) levels were measured at baseline, induction,
      incision and extubation. TIVA produced a significantly lower intubation score,
      shorter time to intubation and faster waking time than VIMA, but recovery
      profiles did not differ. Adrenaline, noradrenaline, cortisol and glucose levels
      were significantly lower with TIVA than VIMA, but there was no difference in IL-6
      levels between the two groups. TIVA with propofol and remifentanil may be
      preferable to VIMA with sevoflurane alone because it leads to smoother, more
      rapid induction, more rapid awakening and lower stress responses to surgical
      stimuli.

PMID- 20146875
TI  - Correlation between pre-operative brain magnetic resonance angiography findings
      and intra-operative cerebral oxygen saturation during coronary artery bypass
      graft surgery.
AB  - Coronary artery bypass graft (CABG) patients often have cerebrovascular disease
      and pre-operative brain magnetic resonance angiography (MRA) frequently reveals
      cerebral vasculature stenosis. This study was designed to investigate whether pre
      operative MRA findings correlated with regional cerebral oxygen saturation
      (ScO(2)) in 120 patients undergoing on-pump or off-pump CABG. Following MRA
      examination, patients were divided into six groups of 20 patients each based on
      MRA findings (no stenosis, mild stenosis or severe stenosis) and procedure (on
      pump or off-pump CABG). Mean ScO(2) values over 3 min were determined at seven
      periods during surgery. Patients with severe cerebrovascular stenosis showed
      significantly lower ScO(2) than other groups during off-pump CABG. During on-pump
      CABG, ScO(2) decreased significantly during cardiopulmonary bypass in all groups
      and was significantly lower in the severe stenosis group. Pre-operative MRA and
      intra-operative ScO(2) monitoring may help to identify patients at increased risk
      of brain damage during or following CABG.

PMID- 20146876
TI  - Effect of maternal stress on fetal heart rate assessed by vibroacoustic
      stimulation.
AB  - This study was designed to determine whether maternal stress levels, state and
      trait anxiety levels, and stress hormones affect fetal heart rate (FHR) patterns
      after vibroacoustic stimulation (VAS) at 30 weeks of gestation. A total of 24
      healthy pregnant women with a single fetus pregnancy were enrolled. Corticotropin
      releasing hormone (CRH) and adrenocorticotropic hormone in maternal plasma and
      cortisol, and chromogranin A in saliva were measured. The FHR patterns after VAS
      were divided into three types: type I, a long period of acceleration or one
      acceleration lasting > 1 min or at least two accelerations lasting > 15 s; type
      II, a biphasic response with acceleration followed by deceleration; and type III,
      no response or prolonged deceleration. In the high trait anxiety group, CRH
      levels were significantly higher than in the low trait anxiety group, and FHR
      patterns after VAS showed mostly a type II response pattern. These findings
      suggest that stress in pregnant women with high trait anxiety may influence FHR
      patterns after VAS.

PMID- 20146877
TI  - The effectiveness of a weak opioid medication versus a cyclo-oxygenase-2 (COX-2)
      selective non-steroidal anti-inflammatory drug in treating flare-up of chronic
      low-back pain: results from two randomized, double-blind, 6-week studies.
AB  - Two 6-week studies compared the analgesic efficacy, tolerability and safety of a
      non-steroidal anti-inflammatory drug (celecoxib 200 mg twice a day [bid]) and an
      opioid (tramadol HCl 50 mg four times a day [qid]) in subjects with chronic low
      back pain (CLBP). Successful responders (primary endpoint) were defined as
      subjects completing 6 weeks of treatment and having > or = 30% improvement on the
      Numerical Rating Scale for pain. A total of 796 and 802 subjects were randomized
      to treatment in study 1 and study 2, respectively. A significantly greater
      percentage of celecoxib-treated subjects were successful responders compared with
      tramadol HCl-treated subjects (study 1: 63.2% versus 49.9%, respectively; study
      2: 64.1% versus 55.1%, respectively). Fewer adverse events (AEs) and serious AEs
      were reported in the celecoxib-treated group. Overall, celecoxib 200 mg bid was
      more effective than tramadol HCl 50 mg qid in the treatment of CLBP, with fewer
      AEs reported.

PMID- 20146879
TI  - Expression of somatostatin receptors in human melanoma cell lines: effect of two
      different somatostatin analogues, octreotide and SOM230, on cell proliferation.
AB  - Somatostatin analogues (SAs) are potential anticancer agents. This study was
      designed to investigate the expression of somatostatin receptors (SSTRs) in
      melanoma cells and the effect of two SAs on cell proliferation and viability.
      Eighteen primary and metastatic human cutaneous melanoma cell lines were treated
      with octreotide and SOM230. Expression of SSTR1, SSTR2, SSTR3 and SSTR5 was
      assessed by real-time polymerase chain reaction. Proliferation, viability and
      cell death were assessed using standard assays. Inhibition was modelled by mixed
      effect regression. Melanoma cells expressed one or more SSTR. Both SAs inhibited
      proliferation of most melanoma cell lines, but inhibition was < 50%. Neither SA
      affected cell viability or induced cell death. The results suggest that melanoma
      cell lines express SSTRs. The SAs investigated, under the conditions used in this
      study, did not, however, significantly inhibit melanoma growth or induce cell
      death. Novel SAs, combination therapy with SAs and their anti-angiogenic
      properties should be further investigated.

PMID- 20146878
TI  - The relationship between adipokines, metabolic parameters and insulin resistance
      in patients with metabolic syndrome and type 2 diabetes.
AB  - This study was designed to investigate the relationship between adipokines in
      metabolic syndrome and insulin resistance. Sixty male and female subjects with or
      without metabolic syndrome and type 2 diabetes were included. The homeostasis
      model assessment of insulin resistance (HOMA-IR) was calculated. Compared with
      lean control subjects, patients with metabolic syndrome and type 2 diabetes had
      lower circulating levels of total adiponectin and high molecular weight (HMW)
      adiponectin, and higher levels of leptin and interleukin-6 (IL-6). Total and HMW
      adiponectin and the adiponectin/leptin (A/L) ratio were negatively correlated
      with HOMA-IR. After adjusting for age and sex, leptin, IL-6 and tumour necrosis
      factor-alpha (TNF-alpha) were positively correlated with HOMA-IR. After also
      adjusting for body mass index, HOMA-IR was found to be independently associated
      with leptin, A/L ratio and TNF-alpha levels. In conclusion, decreased total
      adiponectin and HMW adiponectin and increased leptin and IL-6 levels are
      characteristic of patients with metabolic syndrome and type 2 diabetes.

PMID- 20146880
TI  - The effects of intravesical chemoimmunotherapy with gemcitabine and Bacillus
      Calmette-Guerin in superficial bladder cancer: a preliminary study.
AB  - This prospective study investigated the long-term effects of intravesical
      chemoimmunotherapy with gemcitabine (GEM) and bacillus Calmette-Guerin (BCG; n =
      36) versus BCG alone (n = 51) for the treatment of superficial bladder cancer.
      For the chemoimmunotherapy (GEM + BCG) group, GEM (1000 mg) was instilled
      immediately after transurethral resection of bladder tumour (TURBT) and again
      (2000 mg) 1 week later. From 2 to 7 weeks after TURBT, BCG was instilled into the
      bladder of all patients once weekly. The recurrence-free period of the GEM + BCG
      group (24.13 months) was significantly longer than that of the BCG monotherapy
      group (19.81 months). The overall recurrence rate was similar between the groups,
      although at 6 and 9 months post-TURBT, GEM + BCG produced a significantly lower
      rate of recurrence compared with BCG alone. This study suggests that intravesical
      chemoimmunotherapy with GEM + BCG is effective in reducing early tumour
      recurrence and in prolonging the recurrence-free period of superficial bladder
      cancer.

PMID- 20146881
TI  - Effects of n-3 polyunsaturated fatty acid therapy on plasma inflammatory markers
      and N-terminal pro-brain natriuretic peptide in elderly patients with chronic
      heart failure.
AB  - Several previous studies have suggested that n-3 polyunsaturated fatty acids (n-3
      PUFA) can exert favourable effects in patients with heart failure, but the
      mechanisms involved are not fully understood. This study was designed to
      investigate the effects of n-3 PUFA on circulating inflammatory markers and N
      terminal pro-brain natriuretic peptide (NT-proBNP) in patients with heart
      failure. Seventy-six patients with heart failure were randomly assigned to
      receive 2 g/day of n-3 PUFA or placebo for 3 months. Treatment with n-3 PUFA
      significantly decreased plasma levels of tumour necrosis factor, interleukin-6,
      intercellular adhesion molecule 1 and NT-proBNP. Left ventricular ejection
      fraction showed a small, non-significant improvement. High-sensitivity C-reactive
      protein levels decreased significantly in smokers after n-3 PUFA treatment. Thus,
      n-3 PUFA can reduce levels of plasma inflammatory markers and NT-proBNP as
      biomarkers of risk stratification in patients with heart failure. n-3 PUFA may
      offer a novel therapy for heart failure.

PMID- 20146882
TI  - Down-regulation of SHH/BMP4 signalling in human anorectal malformations.
AB  - The sonic hedgehog homologue (SHH)/bone morphogenetic protein 4 (BMP4) signalling
      pathway is involved in the morphogenesis of many organ systems. This study was
      designed to investigate the expression of SHH/BMP4 pathway components in human
      anorectal malformations (ARMs) and the relationship between expression of their
      genes and the occurrence of ARMs. Expression of SHH, GLI family zinc finger 2
      (GLI2) and BMP4 mRNA in the posterior wall of the terminal rectum in 40 patients
      with ARMs (15 high-type and 25 low-type) and 10 normal controls was assessed by
      reverse transcription-polymerase chain reaction. Levels of SHH, GLI2 and BMP4
      proteins were assessed by immunohistochemistry and Western blotting. The
      expressions of SHH, GLI2 and BMP4 were significantly lower in patients with high
      type compared with those with low-type anomalies and controls. Patients with low
      type ARMs differed from controls only in the expression of GLI2 mRNA. It is
      concluded that down-regulation of the SHH/BMP4 signalling pathway may be related
      to the occurrence of high-type ARMs, but the mechanism responsible for low-type
      ARMs remains unclear.

PMID- 20146883
TI  - Real-time fluorescent quantitative polymerase chain reaction study of polo-like
      kinase-1 in pterygia.
AB  - This study was designed to examine the expression of polo-like kinase 1 (PLK1)
      mRNA in 16 pterygia and 13 normal conjunctival tissue specimens using real-time
      fluorescent quantitative polymerase chain reaction (PCR). Glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) was used as the housekeeping gene. The difference
      in threshold cycle value (DeltaC(t)) was derived for PLK1 and GAPDH for each
      sample assayed, and the difference between the paired samples (DeltaDeltaC(t))
      was calculated. The mean +/- SD DeltaC(t) of PLK1 mRNA was 9.56 +/- 1.30 in
      pterygia compared with 10.71 +/- 1.39 in normal conjunctiva. The expression of
      PLK1 mRNA in pterygium was 2.08 - 2.36 times that in normal conjunctiva; this
      difference was statistically significant. Real-time fluorescent quantitative PCR
      analysis appears to be effective and sensitive when determining the level of PLK1
      mRNA expression. Using this method, it was demonstrated that PLK1 mRNA is over
      expressed in pterygia, indicating a probable role for PLK1 in their development.

PMID- 20146884
TI  - Evaluation of POSSUM in predicting post-operative morbidity in patients
      undergoing pancreaticoduodenectomy.
AB  - The Physiological and Operative Severity Score for the enUmeration of Mortality
      and Morbidity (POSSUM) is a predictive scoring system for post-operative
      morbidity. The present study assessed the value of POSSUM in predicting post
      operative morbidity following pancreaticoduodenectomy (PD). POSSUM scores were
      prospectively calculated for 265 consecutive cases of PD performed between 2005
      and 2007. Expected morbidity was estimated based on POSSUM scores and was
      compared with observed morbidity. Patients were also stratified into one of four
      groups based on their individual POSSUM scores and subsequent risk of morbidity.
      Mean expected morbidity was 43.81% (116 cases) and mean observed morbidity was
      39.62% (105 cases) (no statistically significant difference). It is concluded
      that the POSSUM scoring system has high value for predicting the risk of
      morbidity in PD patients.

PMID- 20146885
TI  - p53, Bcl-2 and AgNOR tissue markers: model approach in predicting prostate cancer
      characteristics.
AB  - The balance between proliferation and apoptosis is represented by changes in the
      expression of the tissue markers, Bcl-2 and p53, and the presence of silver
      stained nucleolar organizing regions (AgNOR) on DNA in prostate adenocarcinomas.
      Identifying a mathematical model that would take into account the opposing nature
      of both processes and relate this to cancer stage and grade would be a useful
      adjunct for studying disease behaviour. This retrospective study investigated
      tissue marker expression in prostate adenocarcinoma biopsy samples from 17
      patients. Staining for p53 was inversely correlated with patient age. Staining
      for Bcl-2 correlated with the presence of advanced metastatic cancer and American
      Joint Committee on Cancer (AJCC) disease stage. A mathematical model was
      developed which combined coded staining intensity data for Bcl-2 and AgNOR, as
      markers of proliferation, and for p53, as a marker of apoptotis. The mathematical
      model significantly correlated with Gleason score, AJCC stage and serum prostate
      specific antigen level, whereas each tissue marker alone did not correlate with
      all these measures.

PMID- 20146886
TI  - Bladder dysfunction in infants with primary vesicoureteric reflux.
AB  - There is growing evidence that bladder dysfunction is a negative prognostic
      factor for spontaneous resolution of vesicoureteric reflux (VUR). This study
      evaluated the prevalence of urodynamic abnormalities in infants with primary VUR
      who were referred over a 4-year period. The urodynamic evaluations and medical
      records of 54 infants with primary VUR (79 ureters with reflux) were reviewed
      prospectively. Urodynamic dysfunction was observed in 46.3% (n = 25) of infants
      with primary VUR; 35.2% (n = 19) had a low bladder capacity and 11.1% (n = 6) had
      a large bladder capacity. All infants with large bladder capacities also had high
      grade (IV - V) VUR. In conclusion, there was a close relationship between bladder
      dysfunction and primary VUR. For that reason, urodynamic testing of infants with
      primary VUR should be performed as part of routine clinical evaluations.

PMID- 20146887
TI  - Genetic polymorphisms of MTHFR and aberrant promoter hypermethylation of the
      RASSF1A gene in bladder cancer risk in a Chinese population.
AB  - Epidemiological studies have shown that folate deficiency increases the risk of
      cancer by affecting DNA repair and methylation. Methylenetetrahydrofolate
      reductase (MTHFR) is a key enzyme in folate metabolism. In this study, it was
      hypothesized that MTHFR (C677T and A1298C) polymorphisms would be associated with
      bladder cancer and also with hypermethylation of the promoter of the Ras
      association domain family 1A (RASSF1A) gene. This hospital-based, case-control
      study of 312 bladder cancer patients and 325 cancer-free controls found that
      individuals carrying the MTHFR 677TT genotype had a 2.00-fold increased risk of
      bladder cancer compared with those carrying the 677CC genotype. None of the MTHFR
      A1298C polymorphisms alone were associated with bladder cancer, but the combined
      haplotype 677TT/1298AA was associated with a 2.27-fold increased risk compared
      with haplotype 677CC/1298AA. There was no association between MTHFR gene variants
      and methylation status of the RASSF1A gene in the 45 bladder cancer patients in
      whom this was studied. It is concluded that the MTHFR 677TT genotype and the TTAA
      haplotype may increase the risk of bladder cancer.

PMID- 20146888
TI  - Comparison of anti-Xa activity after a single intravenous bolus of low-dose
      enoxaparin in patients with and without end-stage renal disease.
AB  - This study was designed to evaluate anti-Xa activity hourly during the first 3 h
      after a single intravenous bolus of 0.5 mg/kg enoxaparin in 30 patients with end
      stage renal disease (ESRD) who underwent haemodialysis, and in 30 patients with
      normal or mildly reduced renal function who underwent coronary angiography for
      chest pain (non-ESRD group). Mean +/- SD haemodialysis time was 3.9 +/- 0.3 h in
      the ESRD group. Of 24 patients diagnosed with coronary artery disease in the non
      ESRD group, 20 underwent percutaneous coronary intervention (PCI). A peak anti-Xa
      activity > 0.5 IU/ml 10 min after enoxaparin injection was obtained in 90% and
      93% of the non-ESRD and ESRD patients, respectively. The percentages of patients
      with peak anti-Xa activity in the target range (0.5 - 1.5 IU/ml) were similar in
      the two groups (non-ESRD 80%, ESRD 93%). Adequate anti-Xa activity (> 0.5 IU/ml)
      lasted about 2 h in both groups. It is concluded that a single intravenous low
      dose enoxaparin (0.5 mg/kg) bolus provides anti-Xa activity adequate for elective
      PCI within 2 h irrespective of whether or not the patient had ESRD.

PMID- 20146889
TI  - Oxidative stress and apoptosis of human brain microvascular endothelial cells
      induced by free fatty acids.
AB  - Damage to endothelial cells is a key event in the pathogenesis of atherosclerosis
      and vascular disease. This study aimed to determine whether free fatty acids
      (FFAs) induced oxidative stress and apoptosis in human brain microvascular
      endothelial cells (HBMVECs) in vitro and, if so, which signalling pathway
      mediated these effects. After culture in different concentrations of FFAs for 24 
      72 h, cell viability/proliferation was determined using a cell counting kit,
      apoptosis was detected by measuring caspase-3 activity and by using annexin V
      conjugated fluorescein isothiocyanate/propidium iodide staining, and oxidative
      stress was evaluated by measuring the levels of reactive oxygen species (ROS) and
      mitochondrial membrane potential (MMP). The HBMVECs exposed to FFAs showed
      significantly decreased cell proliferation, increased apoptosis and ROS levels,
      and decreased MMP. In conclusion, the results showed that high levels of FFAs
      induced oxidative stress, which damaged HBMVECs and resulted in apoptosis.

PMID- 20146890
TI  - Pleiotropic effects of mitiglinide in type 2 diabetes mellitus.
AB  - This study investigated the effects of mitiglinide in 16 patients with type 2
      diabetes mellitus treated with 30 mg/day mitiglinide, divided into three doses
      given just before each meal, for approximately 12 months. A 450 kcal meal
      tolerance test was performed at baseline and after 3, 6 and 12 months, and levels
      of plasma glucose and immunoreactive insulin were measured. Various parameters of
      glucose metabolism and lipid metabolism, urinary albumin and markers of
      atherosclerosis, coagulation and fibrinolysis were also determined. Mitiglinide
      showed a rapid stimulatory effect on insulin secretion and reduced the levels of
      plasma glucose. The free fatty acid level significantly decreased at 60 min after
      the meal tolerance test. Mitiglinide also significantly lowered glycosylated
      haemoglobin and raised 1,5-anhydroglucitol after 6 months, and significantly
      decreased urinary albumin after 12 months. These data indicate that mitiglinide
      may have beneficial effects not only on glycaemic control but also on lipid
      metabolism and urinary albumin excretion, and may have a role in the prevention
      of the vascular complications of diabetes.

PMID- 20146891
TI  - Cerebrospinal fluid cytology and clinical analysis of 34 cases with
      leptomeningeal carcinomatosis.
AB  - The clinical characteristics and cerebrospinal fluid (CSF) cytological features
      of 34 hospitalized patients with leptomeningeal carcinomatosis (LC) were studied.
      Most patients presented with signs of meningeal irritation (19 cases) and intra
      cranial hypertension (23 cases). Computed tomography (CT) and/or magnetic
      resonance imaging (MRI) revealed brain parenchymal lesions, hydrocephalus and
      leptomeningeal enhancement (nine, six and eight cases, respectively). The CSF
      changes included high opening pressure (21 cases), increased white blood cell
      count (23 cases), elevated protein levels (25 cases) and low glucose levels (17
      cases). Malignant cells were found in all CSF specimens and 32 cases had
      malignant cells in their initial CSF examinations. High serum levels of
      carcinoembryonic antigen (CEA) occurred in 11 patients. Signs of meningeal
      irritation and intra-cranial hypertension were common. It is concluded that serum
      CEA measurement along with CT and MRI scanning are helpful in the diagnosis of
      LC. Crucially, however, CSF cytology could be the most important technique for
      the diagnosis of LC.

PMID- 20146892
TI  - Factors affecting prosthetic rehabilitation outcomes in amputees of age 60 years
      and over.
AB  - This retrospective, observational study was designed to investigate factors
      affecting successful prosthetic ambulation in elderly amputees aged > or = 60
      years. The study included 64 unilateral transfemoral or hip disarticulation
      amputees. Patients who were able to walk > or = 100 m with prosthesis were
      classified as successful and those who could walk < 100 m as failures. Age,
      comorbidities, cause of amputation, ability to stand on one leg, patient's
      motivation for walking and maximum oxygen uptake as a proportion of predicted
      maximum oxygen uptake (%VO(2max)) during an exercise load test were examined as
      indicators of physical fitness. Significant differences were noted between the
      two groups in the number of comorbidities, ability to stand on one leg, patient's
      motivation for walking and mean %VO(2max). A low number of comorbidities, the
      ability to stand on one leg, motivation for walking and adequate physical fitness
      allowing an exercise intensity of > or = 50% VO(2max) were considered to be
      predictive factors for successful prosthetic rehabilitation.

PMID- 20146893
TI  - Clinical applications and acute hepatotoxicity of intravenous amiodarone.
AB  - This cross-sectional, retrospective study was designed to evaluate the current
      clinical applications and acute hepatotoxicity of intravenous amiodarone
      administration at a hospital in China. Clinical data were collected from 1214
      patients receiving intravenous amiodarone treatment between October 2003 and
      September 2005. Baseline patient characteristics, drug indications,
      administration records and acute hepatotoxicity associated with the drug were
      examined. Amiodarone was used primarily in arrhythmic patients with obvious
      cardiac dysfunction. Atrial fibrillation and ventricular arrhythmia were the two
      most commonly treated dysfunctions. Incorrect indications and administration
      methods were also noted. Hepatotoxicity occurred in 12.6% of the patients, but
      was mild in most cases. Males showed a higher incidence of hepatotoxicity than
      females. The use of amiodarone was considered to be reasonable and standardized,
      but there was still considerable room for improvement, particularly in the
      standardization of administration guidelines. Intravenous amiodarone can cause
      hepatotoxicity and hepatic function tests should be performed soon after giving
      amiodarone intravenously.

PMID- 20146894
TI  - Efficacy and safety of celecoxib in the treatment of acute pain due to ankle
      sprain in a Latin American and Middle Eastern population.
AB  - Ankle sprains are common acute soft-tissue injuries. This 7-day open-label,
      multicentre, randomized study compared the efficacy and safety of celecoxib with
      non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in treating acute
      ankle sprain with moderate-to-severe ankle pain in 278 patients. Patients
      received either celecoxib (400 mg loading dose followed by 200 mg twice daily) or
      standard doses of non-selective NSAIDs. The primary endpoint was a change in the
      patient's assessment of ankle pain on a 0 mm (no pain) - 100 mm (worst possible
      pain) visual analogue scale (VAS) at day 3 compared with baseline. From a
      baseline of 73 mm, mean VAS pain scores decreased to 29 and 32 mm in the
      celecoxib and non-selective NSAID groups, respectively. The lower limit of the
      95% confidence interval for the treatment difference with regard to change from
      baseline was greater than the pre-established non-inferiority margin of -10 mm.
      Using an initial loading dose, celecoxib was at least as efficacious as non
      selective NSAIDs in treating acute pain due to ankle sprain.

PMID- 20146895
TI  - Identification of acute self-limited hepatitis B among patients presenting with
      hepatitis B virus-related acute hepatitis: a hospital-based epidemiological and
      clinical study.
AB  - This study aimed to identify acute self-limited hepatitis B (ASL-HB) among
      patients presenting with hepatitis B virus (HBV)-related acute hepatitis. Data
      were available for 220 patients diagnosed with HBV-related acute hepatitis, of
      whom 164 had acute hepatitis B (AHB). Of these, 160 were confirmed as ASL-HB:
      three (1.9%) evolved to chronic hepatitis B and one (0.6%) developed fulminant
      hepatitis and died. Comparisons were also made between AHB and acute infections
      with hepatitis A (HA) and hepatitis E (HE) viruses. During the study period, the
      number of patients with AHB exceeded the sum of those with acute HA and acute HE
      infections. There was no distinct seasonal peak for AHB infection, whereas both
      acute HA and acute HE infections occurred more frequently in the spring. Clinical
      symptoms and physical signs were similar for all three types of hepatitis, but
      significant differences were seen in some biochemical parameters. In conclusion,
      this study suggests that symptomatic AHB is not rare in China but it seldom
      evolves to chronic hepatitis B.

PMID- 20146896
TI  - Improved survival in patients with end-stage cancer treated with coenzyme Q(10)
      and other antioxidants: a pilot study.
AB  - This pilot study evaluated the survival of patients with end-stage cancer who
      received supplements of coenzyme Q(10) and a mixture of other antioxidants (e.g.
      vitamin C, selenium, folic acid and beta-carotene). During a period of 9 years,
      41 patients who had end-stage cancer were included. Forty patients were followed
      until death and one patient was lost to follow-up and presumed dead. Primary
      cancers were located in the breast, brain, lungs, kidneys, pancreas, oesophagus,
      stomach, colon, prostate, ovaries and skin. The median predicted survival time
      was calculated from Kaplan-Meier curves for each patient at inclusion. Median
      predicted survival was 12 months (range 3 - 29 months), whereas median actual
      survival was 17 months (1 - 120 months), which is > 40% longer than the median
      predicted survival. Mean actual survival was 28.8 months versus 11.9 months for
      mean predicted survival. Ten patients (24%) survived for less time than
      predicted, whereas 31 (76%) survived for longer. Treatments were very well
      tolerated with few adverse effects.

PMID- 20146897
TI  - Evaluation of the effect of 4 months of risedronate therapy on femoral strength
      using femoral strength analysis tools.
AB  - The effect of risedronate (2.5 mg once daily) on femoral strength was evaluated
      using Advanced Hip Assessment (AHA) for the first time in Japan. In total, 104
      patients with primary osteoporosis and available data on bone mineral density
      (BMD; lumbar spine/proximal femur), urinary NTx (cross-linked N-telopeptides of
      type I collagen) and AHA-based parameters collected before and after 4 months of
      risedronate therapy were included in the analyses. Change and percentage change
      from baseline in these parameters were determined. Percentage change in femur
      strength index was 7.9 +/- 21.1% and 5.5 +/- 18.0% for the right and left femurs,
      respectively; both increases were statistically significant. Cross-sectional
      moment of inertia, cross-sectional area and mean neck width in the femoral neck
      region of interest also increased significantly in both femurs. Percentage change
      in lumbar spine BMD (L2 - L4) was 3.0 +/- 3.7%, and proximal femoral BMD was 1.1
      +/- 3.1% and 0.7 +/- 3.2% in the right and left femurs, respectively, all showing
      a significant increase from baseline. Percentage change in urinary NTx was -41.5
      +/- 30.5%, which was a significant decrease. Using AHA, this study showed that,
      in patients with primary osteoporosis, risedronate improved BMD and bone quality,
      thereby enhancing femoral strength as early as 4 months after treatment
      initiation.

PMID- 20146898
TI  - Effect of 3 months of doxazosin therapy on T-cell subsets in type 2 diabetic
      patients.
AB  - Doxazosin, an alpha(1)-adrenergic receptor inhibitor, is commonly administered to
      patients with type 2 diabetes, hypertension and nephropathy. The impact of 3
      months' doxazosin therapy on the prevalence of activated and regulatory T
      lymphocytes was analysed in this pilot study of men with type 2 diabetes (n = 10)
      who received doxazosin 4 mg/day in addition to their ongoing therapy. The
      prevalence of CD4(+), CD8(+), CD25(+) and CD69(+) cells at baseline and after 3
      months of add-on therapy was determined. The prevalence of regulatory T-cells was
      detected by two different approaches: forkhead box P3 (FoxP3) positivity; and the
      number of CD4(+)CD25(+high) cells. During 3 months of doxazosin therapy,
      patients' blood pressure, blood glucose control and lipid profiles all
      significantly improved. Simultaneously, the prevalence of activated T-cells
      (CD4(+)CD69(+) and CD8(+)CD69(+) cells) decreased, whereas that of regulatory T
      cells increased. These results indicate an immunomodulatory action of doxazosin
      in type 2 diabetic patients.

PMID- 20146899
TI  - Does Ramadan fasting increase acute upper gastrointestinal haemorrhage?
AB  - The epidemiological characteristics and clinical results of patients who
      presented with acute upper gastrointestinal haemorrhage (AUGIH) during the month
      of Ramadan (October 2007) were compared with those who presented with AUGIH
      during another, non-Ramadan, month (December 2007). The following were evaluated:
      age, gender, symptoms, gastrointestinal disease history, risk factors, co
      existing diseases, results of rectal, nasogastric and endoscopic examinations,
      treatment modalities and clinical outcomes. Significantly more patients were
      diagnosed with AUGIH during Ramadan compared with the non-Ramadan month (43
      versus 28, respectively). Significantly more patients diagnosed during Ramadan
      had a history of previous haemorrhage compared with the non-Ramadan month (72.1%
      versus 42.9%, respectively). Peptic ulcer was the most common event in both
      groups and overall endoscopy findings differed between the groups. No other
      significant differences were found. In conclusion, the number of patients
      presenting with AUGIH during Ramadan was significantly higher than that of an
      ordinary month, which suggests that fasting during Ramadan reactivates and
      aggravates pre-existing gastrointestinal diseases.

PMID- 20146900
TI  - Parotid gland metastasis of nasopharyngeal carcinoma: case report and review of
      the literature.
AB  - Parotid metastasis of nasopharyngeal carcinoma (NPC) is extremely rare. The
      current case report presents the history of a 41-year old male with the primary
      symptom of a right parotid gland mass who was diagnosed with NPC by
      histopathology in 2006 and was staged as having cT(3)N(2)M(0) disease (stage III,
      American Joint Committee on Cancer staging system, 2002). Histopathological
      examination of a partial excision of the mass on the right parotid and the
      neoplasm in the pharynx nasalis revealed poorly differentiated squamous cell
      carcinoma. The patient received radiotherapy and concurrent chemotherapy. Grade 2
      skin reaction, grade 2 oropharyngeal mucositis and grade 3 xerostomia were
      detected during treatment. The patient achieved a complete clinical response by 1
      month after treatment. At the last follow-up in August 2009, the patient was in a
      good condition and living a normal life. The primary symptom of parotid gland
      mass in patients with NPC is commonly misdiagnosed and a pathological analysis
      can be considered a reliable method for confirming diagnosis.

PMID- 20146901
TI  - Anaplastic lymphoma kinase expression and prognosis in inflammatory
      myofibroblastic tumours of the maxillary sinus.
AB  - Inflammatory myofibroblastic tumours (IMT) of the nasal cavity and nasal sinus
      are rare and, although over 50 cases have been reported in the English-language
      literature, their precise aetiology and biological behaviour have not been
      elucidated. Recent studies suggest that anaplastic lymphoma kinase (ALK)-positive
      tumours have a very low risk of metastasis, but ALK reactivity does not appear to
      correlate with recurrence. Between March 2002 and December 2008, we encountered
      three cases of maxillary sinus IMT and investigated them to determine the
      clinicopathological course, prognosis and immunohistochemical expression of ALK.
      Two of the patients died < 13 months after the initial diagnosis and the third
      had multiple recurrences. All three cases were immunohisto chemically negative
      for ALK expression. IMT of the sino-nasal tract is rare and may undergo malignant
      transformation in a minority of cases. The three cases manifested progressive
      extension with bone destruction and multiple recurrences, and two cases had a
      fatal outcome and one case had high recurrence.

PMID- 20146902
TI  - A randomised 2 x 2 trial of community versus hospital pulmonary rehabilitation,
      followed by telephone or conventional follow-up.
AB  - OBJECTIVES: To determine whether pulmonary rehabilitation carried out in a
      community setting is more effective than that carried out in a standard hospital
      setting and which is more cost-effective; also whether telephone follow-up is
      both cost-effective and useful in prolonging the beneficial effects of a
      pulmonary rehabilitation programme. DESIGN: A randomised trial. Participants were
      randomised in 2 x 2 factorial fashion to hospital or community rehabilitation and
      telephone or standard follow-up with review. SETTING: Hospitals or community
      sites in Sheffield. The community venues were selected to be close to public
      transport routes and have good parking and level access. The two hospital venues
      were the physiotherapy gym and a staff gym within the grounds of the hospital.
      PARTICIPANTS: Patients with chronic obstructive pulmonary disease diagnosed by
      respiratory physicians according to Global Initiative for Chronic Obstructive
      Lung Disease guidelines. INTERVENTIONS: Participants were randomised to one of
      four groups: hospital rehabilitation with no telephone follow-up; hospital
      rehabilitation with telephone follow-up; community rehabilitation with no
      telephone follow-up; or community rehabilitation with telephone follow-up. All
      were blinded to the telephone intervention arm until 1 month post rehabilitation,
      when only the assessment team and research participants were unblinded. MAIN
      OUTCOME MEASURES: The primary outcome measure was the difference in improvement
      in endurance shuttle walking test (ESWT) between hospital and community pulmonary
      rehabilitation groups post rehabilitation, and the difference in ESWT during 18
      months' follow-up between those receiving telephone encouragement and those
      receiving standard care. A secondary measure was health-related quality of life.
      RESULTS: A total of 240 participants had evaluable data. Of these, 129 were
      randomised to hospital rehabilitation (64 with telephone follow-up and 65 with no
      telephone follow-up) and 111 to community rehabilitation (55 with telephone
      follow-up and 56 with no telephone follow-up). For the primary outcome measure,
      there were 162 patients with data for analysis: hospital rehabilitation with no
      telephone follow-up (n = 38); hospital rehabilitation with telephone follow-up (n
      = 48); community rehabilitation with no telephone follow-up (n = 43); and
      community rehabilitation with telephone follow-up (n = 33). For the acute phase
      post-rehabilitation outcomes, before patients had the opportunity for telephone
      follow-up, we compared outcomes between the 76 patients in the community
      rehabilitation group and the 86 patients in the hospital rehabilitation group.
      Patients in the hospital rehabilitation group increased the distance they could
      walk at the post-rehabilitation follow-up by 283 m (SD 360 m), an increase
      relative to baseline of 109% (SD 137%). Patients in the community rehabilitation
      group increased the distance they could walk at the post-rehabilitation follow-up
      by 216 m (SD 340 m), an increase relative to baseline of 91% (SD 133%). There was
      no statistically significant difference between the groups [17.8% (95% CI -24.3
      to 59.9, p = 0.405)]. For longer term outcomes at 6, 12 and 18 months post
      rehabilitation there was no evidence of a rehabilitation group effect. After
      allowing for the initial post-rehabilitation baseline distance walked, time
      (follow-up visit) and the factorial design (telephone follow-up group), the
      average difference in the post-rehabilitation follow-up distance walked on the
      ESWT between the hospital and community rehabilitation groups was 1.5 m (95% CI 
      82.1 to 97.2, p = 0.971), and between the telephone and no-telephone groups it
      was 56.9 m (95% CI -25.2 to 139, p = 0.174). There was no difference between
      hospital or community groups in terms of acute effect or persistence of effect.
      Health economic analysis favoured neither hospital nor community settings, nor
      did it clearly favour telephone follow-up or routine care. CONCLUSIONS: Pulmonary
      rehabilitation delivered in a community setting has similar efficacy to that
      produced in a more traditional hospital-based setting, both settings producing
      significant improvements in terms of exercise capacity and quality of life
      acutely and after long-term follow-up. Health economic analysis showed that
      neither hospital nor community programmes were greatly favoured. The choice of
      model will depend on local factors of convenience, existing availability of
      resources and incremental costs. Staff characteristics may be important in
      gaining optimal outcome, and care should be taken in staff recruitment and
      training. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86821773.

PMID- 20146903
TI  - [Maybe we change the title of your article].

PMID- 20146904
TI  - [Should all pregnant women be screened for serum ferritin as a part of iron
      deficiency prophylaxis?].

PMID- 20146905
TI  - [Pregnancy and iron prophylaxis--how and how much?].
AB  - Iron is essential for normal foetal development. Iron deficiency anaemia in
      pregnancy is a risk factor for preterm delivery and low birth weight in the
      newborn. Iron supplementation during gestation increases plasma ferritin and
      haemoglobin and reduces the prevalence of iron deficiency anaemia. As from June
      2008, The Danish National Board of Health had been advocating general iron
      prophylaxis in pregnancy with 40 mg ferrous iron from the 10th gestation week to
      delivery. However, the authors suggest that individual prophylaxis according to
      plasma ferritin should be preferred to general prophylaxis.

PMID- 20146906
TI  - [Organisation of basic training in laparoscopic surgery].
AB  - INTRODUCTION: Training, development and implementation of minimally invasive
      surgery is resource-demanding. The new Danish specialist training programme
      combined with shorter employment periods and working hours have increased the
      need for a more efficient education, training and certification of surgery,
      gynaecology and urology trainees. MATERIAL AND METHODS: A total of 106 trainees
      who were non-specialised doctors from a region in Denmark underwent theoretical
      as well as practical specialised training in laparoscopy in the period 2006-2008.
      The training had several modules of which the two first are described. The
      training and evaluation methods used were objective, structured clinical
      examination (OSCE-test) and objective skill assessments tests (OSATS-test).
      RESULTS: Among the 108 trainees, a total of 80 physicians passed. On module 1,
      the distribution of participants with regards to speciality was: surgery 47
      physicians, urology 14 physicians and gynaecology 45 physicians. Six physicians
      were not certified. We have registered OSATS-scores for 64 participants with a
      median score of 3.0 (range 1-4.4). To pass, the multiple choice test participants
      needed to answer 66% of the questions correctly. Below this level were 20
      participants out of 57 (35%) on module 1 and 32 out of 60 (53%) on module 2.
      CONCLUSION: Thanks to political attention and sufficient financing a centre
      without physical premises has been established. It has been possible to offer
      training to young surgeons during their first year with both benchmark training
      and live operations in animal models. The concept may also be used by the trainee
      as guidance when making education and career choices.

PMID- 20146907
TI  - [Necrotizing fasciitis].
AB  - INTRODUCTION: Necrotizing fasciitis (NF) is an acute soft-tissue infection,
      associated with a high mortality and morbidity. To reduce the mortality, an early
      diagnosis and treatment is essential. Our study aims to identify the number of
      patients, the microorganisms involved, and NF treatment outcomes among patients
      admitted to our unit. MATERIAL AND METHODS: This retrospective cohort study
      enrolled 85 patients admitted to the multidisciplinary, tertiary Intensive Care
      Unit, Abdominal Center, Rigshospitalet, Denmark in 2005-2007. All received the
      same protocolled treatment of intensive care, extensive surgical debridements,
      broad-spectrum antibiotics, intravenous immunoglobulin and hyperbaric oxygen.
      RESULTS: The microbiological analyses of specimens demonstrated that 51% were
      positive for polymicrobial infection, 40% for a single pathogen, 74% of these
      caused by beta-hemolytic streptococci, and 9% of the analyses were inconclusive.
      Of the patients, 91% required treatment in a respirator, 67.5% presented with
      septic shock and 25.3% developed acute renal failure needing dialysis. Intensive
      care unit mortality was 6% and 30-day mortality was 9.5%. Expected mortality
      based on SAPS II and APACHE II scoring was 38%. Our patients had a significantly
      higher body mass index than other patients admitted to the unit. CONCLUSION: NF
      is a complex disease, often associated with multi-organ failure. A protocolled
      treatment plan with close cooperation between the intensive care, clinical
      microbiology, medical and surgical specialties seems to reduce mortality
      considerably in this vulnerable group of patients.

PMID- 20146908
TI  - [Support for self-management in chronic disease?].
AB  - Self-management is part of chronic care to ensure an informed and activated
      patient. We scrutinised systematic literature reviews about self-care in general
      practice. There were effects on clinical and patient related measures and health
      services utilisation. Most effect was seen in interventions using health care
      professionals to provide education about action plans and medical treatment.
      Patient led education did not show effect on clinical outcome but on patient
      related measures. We conclude that general practice should implement self
      management as part of chronic care.

PMID- 20146909
TI  - [Detection of postoperative cognitive dysfunction].
AB  - Postoperative cognitive dysfunction (POCD) is a frequent complication to surgery.
      Studies show considerable disagreement concerning the definition of POCD and the
      methods used for its -assessment. Objectivity may be obtained through neuro
      psychological testing, contrary to the use of questionnaires, but several
      methodological issues can potentially affect the results. Aspects like baseline
      performance, practice effects and time interval between test sessions all
      influence the assessment of cognitive function.

PMID- 20146910
TI  - [Lenalidomide in the treatment of transfusion dependent myelodysplastic
      syndromes].
AB  - Lenalidomide is the first drug to induce transfusion independence and cytogenetic
      remission in patients with myelodysplastic syndrome (MDS) with deletion 5q and
      low or intermediate risk score. Transfusion independence can be obtained within
      five weeks. Three out of four patients also obtain a cytogenetic response to
      treatment. However, concern has arisen about the possibility of an increased risk
      of transformation to acute myeloid leukaemia. A multicenter, randomised, placebo
      controlled study with long-term follow-up is needed.

PMID- 20146911
TI  - [Surgical treatment of female urinary incontinence].
AB  - INTRODUCTION: During the last decade, minimal invasive procedures have been
      introduced for treatment of urinary incontinence (UI) in women leading to shorter
      hospitalisation and fewer complications. The aim of this study was to outline
      clinical practice and attitudes among Danish UI surgeons. MATERIAL AND METHODS:
      Surgeons performing UI procedures were identified and mailed a questionnaire in
      2007 concerning 2006. Questions included specialisation, number of procedures,
      type of surgery, complications and attitude towards learning surgery and
      maintaining a sufficient level of routine. RESULTS: In total, 94 operating
      gynaecologists and urologists were identified, 63 responded (71%) of whom 49
      (78%) performed UI surgery. UI surgeons were gynaecologists 43 (88%) of these 24
      (49%) were urogynecologists (working more than 50% with urogynecology) and five
      (10%) urologists. Tension-free Vaginal Tape (TVT) was the preferred sling in
      2006. A total of 20 (47%) UI surgeons used only TVT, seven (17%) only
      transobturator slings (TOS) and 15 (36%) both TVT and TOS. Only 11 (24%)
      performed > 25 TVT per year and 11 (27%) performed > 25 TOS per year. In all, UI
      surgeons had experience with ten different slings. This study did not allow for a
      quantitative assessment of complications. The attitude was that 10-25 operations
      are needed to learn the procedure, and that > 10 operations per year are needed
      to maintain a sufficient level of routine. CONCLUSION: Practice and attitudes
      among urinary incontinence surgeons vary considerably and there is a lack of
      consensus. Many UI surgeons perform few operations with different techniques.

PMID- 20146912
TI  - [Ketamine in melancholic depression].
AB  - A 35-year-old male known with bipolar disorder was admitted after a suicide
      attempt with cuts in both wrists. The patient had a major depression with
      melancholic symptoms and nihilistic delusions. To relieve the patient's agony in
      the days before electroconvulsive therapy and to reduce the risk of suicide, the
      patient was treated with S-ketamine 0,5 mg/kg. The patient's symptoms were
      reduced two hours after treatment and the effect was measurable for five days.

PMID- 20146913
TI  - [Meningioma as the cause of ear problems].
AB  - A 45-year-old woman with long-term unilateral ear problems, hearing loss, vertigo
      and tinnitus was diagnosed with a meningioma in the middle ear. Magnetic
      resonance imagining (MRI) revealed that the meningioma penetrated the petrous
      bone into the middle ear. The meningioma was removed to avoid further hearing
      loss. Patients with long-term unilateral ear problems that are resistant to
      conventional therapy should be referred to computed tomography, MRI and
      explorative tympanotomy. Surgery is indicated if progressions in neurological
      deficits are seen, but surgery may cause serious neurological deficits.

PMID- 20146914
TI  - [Blunt laryngeal trauma].
AB  - This case report highlights laryngeal trauma and stresses the importance of this
      type of trauma in the emergency room setting. This case report describes an 18
      year-old girl who receives a trauma to the larynx and subsequently dies of an
      infarction of the cerebellum.

PMID- 20146915
TI  - [Dementia and pain].
AB  - Dementia has been associated with disturbed pain processing and an impaired
      ability to provide self-reported ratings on pain. Patients with cognitive
      impairment have been shown to receive pain treatment less frequently than
      cognitively unimpaired individuals. Comorbidity is common in patients with
      dementia and a major factor contributing to pain. This demonstrates that a
      structured evaluation and categorisation of pain is mandatory for the treatment
      of older patients and that care should be taken to note indirect signs of pain.
      The appropriate scales are available and we propagate their application.
      Multimodal pain therapy is superior to one-dimensional approaches. A discussion
      of the effects and interactions of the analgesics presently available for
      geriatric care forms an integral part of this review.

PMID- 20146916
TI  - [Is our clinical practice of antipsychotic relapse prevention in schizophrenia
      really evidence-based].
AB  - OBJECTIVE, METHODS: Relapse prevention is one of the central issues in the
      treatment of schizophrenic psychoses. The paper gives an overview of the current
      literature on medication adherence with special regard to 2nd generation
      antipsychotics and long-acting agents and describes the practical consequences
      for clinical routine. Additionally, it examines whether or not everyday practice
      is consistent with our actual scientific knowledge. RESULTS: Even in shortterm
      trials, medication adherence in patients with schizophrenia comes up to merely
      50%. The negative consequences of medication non-adherence are substantial. This
      concerns the rates of relapse and readmission, morbidity and mortality, - in
      particular suicide -, as well as the economic burden of society. Consequent
      antipsychotic treatment is associated with significantly better outcomes in all
      dimensions. In this regard, longacting agents are unequivocally superior to oral
      antipsychotics - even to atypical ones. These facts conflict with clinical
      routine, where long-acting antipsychotic agents are scarcely used. CONCLUSIONS:
      Based on current scientific knowledge, the major objections raised against the
      application of long-acting agents can be refuted: 1) 2nd generation
      antipsychotics do not improve medication adherence. 2) Concerns that long-acting
      agents conflict with the autonomy of a patient neglect the loss of autonomy and
      self-determination in case of a psychotic relapse. 3) The assertion that the
      patients do not accept depot injections is simply untrue. Rather, it is the
      psychiatrists who have their (maybe primarily emotionally-based) reservations. In
      summary, the use of depot antipsychotics has important advantages in facilitating
      relapse prevention and should be considered for every patient for whom long-term
      antipsychotic treatment is indicated.

PMID- 20146917
TI  - [Usage of inpatient treatments after reduction of inpatient capacities: Supply
      influences demand].
AB  - OBJECTIVE: Next to socio-economic factors, subjective need, political and health
      economiaspects play an important role in the planning of psychiatric structures.
      The aim of this study was to assess the consequences of a reduction of inpatient
      capacities fort the usage of psychiatric inpatient care. METHODS: The admissions
      of inpatients from a region in which the inpatient service has been replaced by
      the inpatient service from another region in the canton of Zurich, Switzerland,
      has been analysed. RESULTS: Within the first two years after the omission of the
      service the admissions of patients with social health insurance policies from the
      relative sector decreased significantly as compared to the rest of the canton. In
      contrast to this, admissions of patients with private health insurances from the
      relative region and from the rest of the canton increased in a similar way.
      CONCLUSION: It can be stated that in the first time after a reduction of
      inpatient capacities patients with social health insurance policies do not use
      inpatient alternatives even when these are easily accessible. This finding is
      meaningful for the arrangement of alternative offers for this very large group of
      patients in psychiatric health care planning.

PMID- 20146918
TI  - [Mental health beliefs between culture and subjective illness experience].
AB  - OBJECTIVE: Subjective health beliefs are representations about pathogenesis,
      course and treatment options of psychic as well as somatic illnesses. They are
      important for a psychotherapeutic interaction as well as for a stable drug
      adherence. However, it remains unclear whether these representations are
      primarily affected by the cultural background or by an individual's specific
      illness experiences, a question of increasing importance in our era of globalized
      migration. METHOD: The study sample consisted of 203 Austrians (125 with
      schizophrenia, 78 with obsessivecompulsive disorder) and 190 Pakistanis (120 with
      schizophrenia, 70 with obsessive-compulsive disorder). All patients completed the
      "Causal Explanations of Mental Disorders" (CEMD), a 41-item self-rating
      questionnaire. RESULTS: Pakistani patients reported magic-religious oriented
      mental health beliefs more frequently. In contrast, Austrians' beliefs are more
      often in line with the bio-psychosocial explanations of Western medicine.
      Concerning mental health beliefs the cultural background seems to be more
      important than the subjective experience with a distinctive mental disorder.
      CONCLUSIONS: Although the subjective experience is of importance for the shape of
      illnessspecific cognitions, mental health beliefs are primarily caused by the
      patients' socio-cultural origin. It is a challenge for psychiatry to improve the
      co-operation with culture-anthropology and other social sciences.

PMID- 20146919
TI  - [Direct health-related costs of severely mentally ill patients and their informal
      carers in community care].
AB  - OBJECTIVE: Within the last few years, a small number of German cost analyses of
      patients treated in community mental health care settings was presented. None of
      these studies, however, examined direct health care costs of the patients' close
      reference persons focusing on costs associated with providing informal care.
      Therefore, our study aimed to analyse health-related direct costs of severely ill
      patients suffering from affective or schizophrenic disorders, and of their
      informal carers during community mental health care; further, we examined if
      these costs differed between the diagnostic groups. METHODS: 69 patients
      currently treated by community mental health services of the Dresden region and
      their closest reference person providing informal care were assessed twice within
      an interval of 3 months by use of the CSSRI- D. Thus, direct health care costs of
      patients and their informal carers covering a 6-months-period could be
      calculated. RESULTS: 25.35% and 38.24%, respectively, of the closest reference
      persons' direct health care costs were caused by the situation of acting as
      informal carer. This was 9.12% and 22.74%, respectively, of the patients' direct
      health care costs assessed at the same time-points. Patients' costs did not
      differ between the diagnostic categories, but were influenced by the current
      severity of psychopathological symptoms. Reference persons' costs were influenced
      by the severity of the patient's psychopathological symptoms, but also by the
      social control behaviour of the reference persons themselves as well as by their
      sense of coherence. CONCLUSIONS: While a replication of our findings is urgently
      needed, they point at the economic significance of direct health-related costs
      caused by acting as informal carers. Further, therapeutic approaches adequate for
      minimizing these costs could be suggested, like emphasizing protective factors of
      mental well-being in psycho-educational programmes for relatives.

PMID- 20146920
TI  - [Patients with mood disorders admitted for a suicide attempt to an emergency
      ward].
AB  - AIM: The aim of the study was to assess risk factors associated with suicidal
      behaviour in adult patients suffering from major mood disorders (MD) and admitted
      to a hospital emergency department (ED). METHODS: Participants were 283 adult
      patients with MDs admitted to an ED between 2006-2007. Comparisons were 675 adult
      patients with other DSM-IV-TR Axis I disorders. Patients undertook a complete
      psychiatric assessment including DSM-IV-TR diagnostic interview. RESULTS: MD
      patients were almost 2 times more likely to have been admitted for a suicide
      attempt (odds ratio [OR]=1,97 [95% confidence intervals [CI]: 1,29/3,03]; p<
      0,01), to report suicidal ideation at the psychiatric interview (OR=1,75 [95%CI:
      1,01/3,03]; p< 0,05), than their pairs without MDs. MD patients admitted for a
      suicide attempt were more than 3 times more likely to report suicidal ideation at
      the psychiatric interview (OR=3,26 [95%CI: 1,46/7,30]; p< 0,01), than
      nonattempter MD patients. DISCUSSION: Suicide behavior is one of the major
      reasons of use of EDs in MDs, and suicide risk is still high in the next hours
      after suicide attempt and admission in the ED. Therefore ED's interventions for
      mood disorders and suicidality must be carefully planned.

PMID- 20146921
TI  - [Von Economo neurons and insular cortex - the bridge between soma and psyche].
AB  - New research suggests a pivotal role of the anterior insular cortex for the
      integration of somatic sensation and for intuitive decisions in complex social
      situations. Functional magnetic resonance imaging (fMRI) has demonstrated a close
      coupling between the anterior insular cortex and the anterior cingulate gyrus,
      the only areas with von Economo-neurons. These large spindle cells are
      exclusively found in species with complex social lifes (apes, cetaceans).
      Observations in humans showed decreased numbers of von Economo neurons in
      patients with frontotemporal dementia, or agenesis of the corpus callosum,
      conditions with impaired theory of mind and interpersonal behaviour. It almost
      appears as if spindle cells would reach out from the realm of subconscious gut
      feelings into the premises of conscious prefrontal planning.

PMID- 20146922
TI  - The functional Toll-like receptor 4 Asp299Gly polymorphism is associated with
      lower left ventricular mass in hypertensive women.
AB  - BACKGROUND: This study investigated the impact of a putative functional TLR4
      polymorphism (Asp299Gly) on left ventricular (LV) structure in hypertensive
      subjects. METHODS: A sample of 443 patients (266 women and 177 men) was evaluated
      by clinical history, physical examination, anthropometry, analysis of
      inflammatory and metabolic parameters, echocardiography and TLR4 Asp299Gly
      genotyping. In addition, the relationship between the polymorphism and in vitro
      lipopolysaccharide responsiveness of peripheral blood monocytic cells was also
      assessed. RESULTS: Women carrying the 299Gly allele presented lower posterior
      wall thickness (p=0.01), interventricular septum thickness (p=0.04), LV mass
      (p=0.01) and LV mass index (p=0.03), as well as a reduced prevalence of LV
      hypertrophy (p=0.002), in comparison to women with the wild-type genotype. These
      results were confirmed by stepwise and logistic regression analyses adjusted for
      potential confounders. Conversely, the 299Gly allele did not influence LV
      structure in men. Furthermore, in vitro assays revealed that monocytes of either
      men or women heterozygous for the 299Gly allele presented a lower
      lipopolysaccharide-induced production of interleukin-6, compared to non-carriers.
      CONCLUSIONS: The functional TLR4 Asp299Gly polymorphism is associated with lower
      LV mass in hypertensive women. These findings suggest that interactions among
      gender, LV remodeling and TLR4 gene variants may occur in hypertensive subjects.

PMID- 20146923
TI  - Eimeria acervulina: the influence of inoculation dose on transmission between
      broiler chickens.
AB  - The course and clinical appearance of an Eimeria species infection in chicken
      flocks depend on the response of an individual bird to infection and on
      population-dynamics of the infection in the flock. Differences in ingested
      numbers of oocysts may affect oocyst load in the flock and the subsequent
      infectious dose for not yet infected birds. To study the link between numbers of
      oocysts excreted by infected birds and transmission of Eimeria acervulina,
      experiments were carried out with 42 pairs of broiler chickens using inoculation
      doses with 5, 50, 500 or 50,000 sporulated oocysts. In each pair one bird was
      inoculated and the other bird was contact-exposed. All contact birds became
      infected, which occurred on average within 34h after exposure to an inoculated
      bird. Although a higher inoculation dose resulted in higher oocyst excretion in
      inoculated and contact-infected birds, only small non-significant differences in
      transmission rates between groups were found.

PMID- 20146924
TI  - Acanthamoeba castellanii: morphological analysis of the interaction with human
      cornea.
AB  - The present study demonstrates that when Acanthamoeba castellanii trophozoites
      are co-cultivated with isolated human corneas, the amoeba can be invasive and
      cause damage to the intact corneal epithelium without the requirement of previous
      corneal abrasion. After adhesion, A. castellanii trophozoites migrate between
      cells forming bumps on the corneal cell layers and reaching Bowman s membrane in
      3h, although no evidence of cell damage was observed until the phagocytic process
      was detected. Likewise, conditioned medium produced damage to the corneal cells
      that was proportional to the time of incubation, but this cytophatic effect
      involved only the most superficial layer of the human cornea and was not enough
      to explain amoebic invasion of Bowman s membrane. As a result of our
      observations, we suggest that the mechanical action of the trophozoites and
      phagocytosis of corneal cells during the process of corneal invasion are more
      important than previously suggested.

PMID- 20146925
TI  - The Cvt pathway as a model for selective autophagy.
AB  - Autophagy is a highly conserved, ubiquitous process that is responsible for the
      degradation of cytosolic components in response to starvation. Autophagy is
      generally considered to be non-selective; however, there are selective types of
      autophagy that use receptor and adaptor proteins to specifically isolate a cargo.
      One type of selective autophagy in yeast is the cytoplasm to vacuole targeting
      (Cvt) pathway. The Cvt pathway is responsible for the delivery of the hydrolase
      aminopeptidase I to the vacuole; as such, it is the only known biosynthetic
      pathway that utilizes the core machinery of autophagy. Nonetheless, it serves as
      a model for the study of selective autophagy in other organisms.

PMID- 20146926
TI  - Positive contribution of the IRE1alpha-XBP1 pathway to placental expression of
      CEA family genes.
AB  - Inositol requiring enzyme-1alpha (IRE1alpha) is an ER-located transmembrane RNase
      whose activation leads to the production of the transcription factor X-box
      binding protein 1 (XBP1). Recently, we showed that the IRE1alpha-XBP1 pathway
      plays an essential role in the placenta. However, details of its function remain
      unclear. To address this point, we searched for IRE1alpha- or XBP1-regulated
      genes in the placenta, and identified the CEA family as a novel target of the
      IRE1alpha-XBP1 pathway. Moreover, PSG genes, which also belong to the CEA family,
      were up-regulated by XBP1. We have therefore identified a new aspect of the
      physiological function of the IRE1alpha-XBP1 pathway in the placenta.

PMID- 20146927
TI  - The stem cell journey: from paradise to purgatory.

PMID- 20146929
TI  - Integral biomathics: a post-Newtonian view into the logos of bios.
AB  - This work is an attempt for a state-of-the-art survey of natural and life
      sciences with the goal to define the scope and address the central questions of
      an original research program. It is focused on the phenomena of emergence,
      adaptive dynamics and evolution of self-assembling, self-organizing, self
      maintaining and self-replicating biosynthetic systems viewed from a newly
      arranged perspective and understanding of computation and communication in the
      living nature. The author regards this research as an integral part of the
      emerging discipline of nature-inspired or natural computation, i.e. computation
      inspired by or occurring in nature. Within this context, he is interested in
      studies which represent a significant departure from traditional theories about
      complex systems and self-organization, emergent phenomena and artificial biology.
      In particular, these include non-conventional approaches exploring the
      aggregation, composition, growth and development of physical forms and
      structures, autopoiesis along with the associated abstract information structures
      and processes. This paper provides a critical review of the major assumptions
      which guide the development of modern computer science and engineering towards
      emulating biological systems. For this purpose, the author explores the potential
      and the virtues of biology to reshape contemporary science. The goal of this
      survey is to discuss the present state of natural and engineering sciences in the
      light of a necessary paradigm change in the structure and methodology of research
      and deliver some insights for developing a new kind of integral science based on
      the principles for dynamic interdependence of the constituting disciplines and on
      the evolving relationships among them.

PMID- 20146930
TI  - Determination of biogenic amines in Korean traditional fermented soybean paste
      (Doenjang).
AB  - Biogenic amines, produced by bacterial decarboxylation of amino acids, have been
      associated with toxicological symptoms in food products. Twenty-three samples of
      traditionally available Korean fermented soybean paste samples (Doenjang) were
      analyzed in order to determine the content of biogenic amines. Amines were
      extracted with 0.4M perchloric acid and derivatized with dansyl chloride. Nine
      biogenic amines were separated from Doenjang samples by high performance liquid
      chromatography using gradient elution (acetonitrile and ammonium acetate), and
      detected with spectrophotometric UV-vis detection at 254 nm. The pH value of all
      the samples was ranged from 4.8 to 6.0, and the strong amino acid decarboxylase
      activity was found to be in an acidic environment. The mean values of biogenic
      amines (tryptamine, 2-phenyl-ethylamine, putrescine, cadaverine, agmatine,
      histamine, tyramine, spermidine and spermine) determined in 23 Doenjang samples
      were found to be 18.37, 82.03, 70.84, 34.24, 47.32, 26.79, 126.66, 74.41 and
      244.36 mg%, respectively. The findings of this study enhance the safety of not
      only Doenjang but other salted and/or fermented food products.

PMID- 20146928
TI  - Recent advancements in stem cell and gene therapies for neurological disorders
      and intractable epilepsy.
AB  - The potential applications of stem cell therapies for treating neurological
      disorders are enormous. Many laboratories are focusing on stem cell treatments
      for CNS diseases, including spinal cord injury, Amyotrophic lateral sclerosis,
      Parkinson's disease, Huntington's disease, multiple sclerosis, stroke, traumatic
      brain injury, and epilepsy. Among the many stem cell types under testing for
      neurological treatments, the most common are fetal and adult brain stem cells,
      embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells.
      An expanding toolbox of molecular probes is now available to allow analyses of
      neural stem cell fates prior to and after transplantation. Concomitantly,
      protocols are being developed to direct the fates of stem cell-derived neural
      progenitors, and also to screen stem cells for tumorigenicity and aneuploidy. The
      rapid progress in the field suggests that novel stem cell and gene therapies for
      neurological disorders are in the pipeline.

PMID- 20146931
TI  - Cranberry (Vaccinium macrocarpon) protects against doxorubicin-induced
      cardiotoxicity in rats.
AB  - Doxorubicin (DOX) is a widely used cancer chemotherapeutic agent. However, it
      generates free oxygen radicals that result in serious dose-limiting
      cardiotoxicity. Supplementations with berries were proven effective in reducing
      oxidative stress associated with several ailments. The aim of the current study
      was to investigate the potential protective effect of cranberry extract (CRAN)
      against DOX-induced cardiotoxicity in rats. CRAN was given orally to rats
      (100mg/kg/day for 10 consecutive days) and DOX (15mg/kg; i.p.) was administered
      on the seventh day. CRAN protected against DOX-induced increased mortality and
      ECG changes. It significantly inhibited DOX-provoked glutathione (GSH) depletion
      and accumulation of oxidized glutathione (GSSG), malondialdehyde (MDA), and
      protein carbonyls in cardiac tissues. The reductions of cardiac activities of
      catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and
      glutathione reductase (GR) were significantly mitigated. Elevation of cardiac
      myeloperoxidase (MPO) activity in response to DOX treatment was significantly
      hampered. Pretreatment of CRAN significantly guarded against DOX-induced rise of
      serum lactate dehydrogenase (LDH), creatine phosphokinase (CK), creatine kinase
      MB (CK-MB) as well as troponin I level. CRAN alleviated histopathological changes
      in rats' hearts treated with DOX. In conclusion, CRAN protects against DOX
      induced cardiotoxicity in rats. This can be attributed, at least in part, to
      CRAN's antioxidant activity.

PMID- 20146932
TI  - A 90 days oral toxicity of imidacloprid in female rats: morphological,
      biochemical and histopathological evaluations.
AB  - A 90 days oral toxicity study of imidacloprid was conducted in female rats with
      doses of 0, 5, 10, 20mg/kg/day. Decrease in the body weight gain was observed at
      20mg/kg/day and at necropsy the relative body weights of liver, kidney and
      adrenal was also significantly increased at this dose level. No mortality
      occurred during treatment period while food intake was reduced at high dose
      level. In clinical chemistry parameters high dose of imidacloprid has caused
      significant elevation of serum GOT, GPT, glucose and BUN and decreased the
      activity of AChE in serum and brain. The spontaneous locomotor activity was also
      decreased at highest dose exposure where as there were no significant changes in
      hematological and urine parameters. The brain, liver and kidney of rats exposed
      with high dose of imidacloprid had showed mild pathological changes. Based on the
      morphological, biochemical, hematological and neuropathological studies it is
      evident that imidacloprid has not produced any significant effects at 5 and
      10mg/kg/day doses but induced toxicological effects at 20mg/kg/day to female
      rats. Hence, 10mg/kg/day dose may be considered as no observed effect level
      (NOEL) for female rats.

PMID- 20146933
TI  - Erythrophagocytosis by angiogenic endothelial cells is enhanced by loss of
      erythrocyte deformability.
AB  - OBJECTIVE: Angiogenic endothelial cells can function as phagocytes, and
      phagocytosis is initiated via the opsonin lactadherin. In this study, we examined
      the interaction between lactadherin-opsonized erythrocytes with reduced
      deformability and angiogenic endothelium, as loss of deformability is
      characteristic for suicidal and aged erythrocytes. MATERIALS AND METHODS: We used
      the Arg-Gly-Asp (RGD)-modified erythrocyte model and investigated the
      deformability parameter by cross-linking erythrocyte membranes through treatment
      with glutaraldehyde. Association in vitro with primary endothelial cells was
      detected by flow cytometry and visualized by light, fluorescent, and electron
      microscopy. Involvement of two crucial factors in phagocytosis, alpha(v)
      integrins and Rho guanosine triphosphatase family member Rac1, was studied using
      small interfering RNA technology. Modified erythrocytes were administered in vivo
      into tumor-bearing mice to detect phagocytosis by endothelial cells. RESULTS:
      Glutaraldehyde-treated (rigid) RGD-modified erythrocytes showed a strongly
      enhanced endothelial cell association compared to flexible RGD-modified
      erythrocytes. Knockdown by small interfering RNA lipoplexes of alpha(v)-integrins
      and Rac1 confirmed classical tethering and internalization of rigid RGD
      erythrocytes. Upon in vivo administration, tumor endothelium showed pronounced
      erythrophagocytosis. CONCLUSION: The pronounced phagocytosis of opsonized
      erythrocytes with reduced deformability by angiogenic growth factor-activated
      endothelial cells evokes new insights in endothelial cell function and suggests a
      role for these endothelial cells in (hematological) disorders because of their
      capacity to clear disordered erythrocytes.

PMID- 20146934
TI  - Measuring the quasi-static Young's modulus of the eardrum using an indentation
      technique.
AB  - Accurate estimation of the quasi-static Young's modulus of the eardrum is
      important for finite-element modeling. In this study, we adapted a tissue
      indentation technique and inverse finite-element analysis to estimate the Young's
      modulus of the eardrum. A custom-built indentation apparatus was used to perform
      indentation testing on seven rat eardrums in situ after immobilizing the malleus.
      Testing was done in most cases on the posterior pars tensa. The unloaded shape of
      each eardrum was measured and used to construct finite-element models with
      subject-specific geometries to simulate the indentation experiment. The Young's
      modulus of each specimen was then estimated by numerically optimizing the Young's
      modulus of each model so that simulation results matched corresponding
      experimental data. Using an estimated value of 12 microm for the thickness of
      each model eardrum, the estimated average Young's modulus for the pars tensa was
      found to be 21.7+/-1.2 MPa. The estimated average Young's modulus is within the
      range reported in some of the literature. The estimation technique is sensitive
      to the thickness of the pars tensa used in the model but is not sensitive to
      relatively large variations in the stiffness of the pars flaccida and manubrium
      or to the pars tensa/pars flaccida separation conditions.

PMID- 20146935
TI  - Differences in gene expression between the otic capsule and other bones.
AB  - Our long term goal is to understand the molecular pathology of otosclerosis and
      to develop better forms of therapy. Toward this goal, the current study focused
      on characterizing the molecular factors responsible for the unique biological
      features of the otic capsule: its minimal rate of remodeling, and lack of healing
      capacity when fractured. We compared expression levels of 62 genes involved in
      bone metabolism between the adult murine otic capsule and the tibia and parietal
      bones; the latter exemplify bones formed by endochondral and intramembranous
      ossification, respectively. Gene expression levels were measured using real-time
      quantitative RT-PCR and analyzed using tools of bioinformatics. Expression
      patterns of key genes were verified with in situ hybridization. The molecular
      profile of the otic capsule was distinctly different from that of the tibia and
      parietal bone. Genes found to be most characteristic of the otic capsule were:
      osteoprotegerin (opg), bone morphogenetic protein receptor 1b (bmpr1b) and bone
      morphogenetic protein 3 (bmp3). Expression levels were high for opg and bmpr1b,
      and minimal for bmp3 within the otic capsule. We concluded that opg and bmpr1b
      likely play important roles in inhibition of remodeling within the otic capsule.

PMID- 20146936
TI  - Oxygen tolerance and occurrence of superoxide dismutase as an antioxidant enzyme
      in Metopus es.
AB  - The free-living anaerobic ciliate Metopus es was found to possess moderate
      tolerance to oxygen. Direct oxygen exposure led to the death of >80% of the
      population within 24h, but the remaining cells exhibited some oxygen tolerance
      and survived up to 4 days without any growth. Survival of the ciliate was
      observed only in an oxygen tension up to 7.0microM, and higher O(2)
      concentrations (>7.0microM) were found to be detrimental with a K(m) value of
      3.5microM. The percentage of survival (50%) was higher when the culture was
      exposed to a low oxygen level (1.3microM) and it decreased with increasing oxygen
      tension. No catalase activity was detected in the extract of surviving ciliates.
      Maximum superoxide dismutase (SOD) activity of 1.52+/-0.4U/mg protein was
      observed at 1.3microM oxygen. SOD activity was not affected by cyanide or
      hydrogen peroxide, indicating that it belongs to the Mn type of SOD. Methanogenic
      endosymbionts in M. es lost their autofluorescence on oxygen exposure of
      >5.0microM, but their viability was not permanently affected, as indicated by the
      maintenance of a similar number of methanogens/cell upon restoring the anaerobic
      condition.

PMID- 20146937
TI  - Proteomic study of linuron and 3,4-dichloroaniline degradation by Variovorax sp.
      WDL1: evidence for the involvement of an aniline dioxygenase-related
      multicomponent protein.
AB  - A proteomic approach was used to explore the metabolism of the phenylurea
      herbicide linuron and 3,4-dichloroaniline (3,4-DCA) in Variovorax sp. WDL1. This
      bacterium grows on linuron as sole source of carbon, nitrogen and energy, while
      it transiently accumulates 3,4-DCA as a metabolite. Differential protein
      expression analysis of Variovorax sp. WDL1 grown in a heterotrophic medium in the
      presence and absence of linuron or 3,4-DCA was conducted using 2-D PAGE. Selected
      up- and downregulated proteins were identified with nanoLC-ESI-MS/MS. In the 3,4
      DCA-supplemented culture, upregulation of several proteins showing high amino
      acid sequence similarity to different components of the multicomponent aniline
      dioxygenase in aniline-degrading Proteobacteria was observed. For one of the
      components, multiple variant proteins were detected, suggesting that strain WDL1
      harbors several copies of the aniline dioxygenase (AD) gene cluster which are
      simultaneously expressed in the presence of 3,4-DCA. A number of unidentifiable
      proteins, which were upregulated in the linuron- and/or 3,4-DCA-supplemented
      cultures, might represent up to now uncharacterized proteins with a role in
      linuron and/or 3,4-DCA degradation in strain WDL1. In addition, several stress
      related proteins were differentially expressed.

PMID- 20146938
TI  - ScreenClust: Advanced statistical software for supervised and unsupervised high
      resolution melting (HRM) analysis.
AB  - BACKGROUND: High resolution melting (HRM) is an emerging new method for
      interrogating and characterizing DNA samples. An important aspect of this
      technology is data analysis. Traditional HRM curves can be difficult to interpret
      and the method has been criticized for lack of statistical interrogation and
      arbitrary interpretation of results. METHODS: Here we report the basic principles
      and first applications of a new statistical approach to HRM analysis addressing
      these concerns. Our method allows automated genotyping of unknown samples coupled
      with formal statistical information on the likelihood, if an unknown sample is of
      a known genotype (by discriminant analysis or "supervised learning"). It can also
      determine the assortment of alleles present (by cluster analysis or "unsupervised
      learning") without a priori knowledge of the genotypes present. CONCLUSION: The
      new algorithms provide highly sensitive and specific auto-calling of genotypes
      from HRM data in both supervised an unsupervised analysis mode. The method is
      based on pure statistical interrogation of the data set with a high degree of
      standardization. The hypothesis-free unsupervised mode offers various
      possibilities for de novo HRM applications such as mutation discovery.

PMID- 20146939
TI  - Analysis of circulating microRNA biomarkers in plasma and serum using
      quantitative reverse transcription-PCR (qRT-PCR).
AB  - MicroRNAs (miRNAs) are small (approximately 22 nt) RNAs that play important roles
      in gene regulatory networks by binding to and repressing the activity of specific
      target mRNAs. Recent studies have indicated that miRNAs circulate in a stable,
      cell-free form in the bloodstream and that the abundance of specific miRNAs in
      plasma or serum can serve as biomarkers of cancer and other diseases. Measurement
      of circulating miRNAs as biomarkers is associated with some special challenges,
      including those related to pre-analytic variation and data normalization. We
      describe here our procedure for qRT-PCR analysis of circulating miRNAs as
      biomarkers, and discuss relevant issues of sample preparation, experimental
      design and data analysis.

PMID- 20146940
TI  - Circulating nucleic acids in cancer and pregnancy.
AB  - Circulating nucleic acids are present in the blood of humans and other
      vertebrates. During the last 10 years researchers actively studied cell-free
      nucleic acids present in plasma or serum with great expectations of their use as
      potential biomarkers for cancer and other pathologic conditions. In the present
      manuscript the main findings related to the principal characteristics of
      circulating nucleic acids, the hypothesis on their origin and some methodological
      considerations on sample collection and extraction as well as on some innovative
      assay methods have been summarized. Recent reports on the importance of
      circulating nucleic acids in the intercellular exchange of genetic information
      between eukaryotic cells have been reviewed.

PMID- 20146941
TI  - Autoimmunity, autoinflammation and lymphoma in combined immunodeficiency (CID).
AB  - A number of primary immunodeficiencies are associated with autoimmune phenomena,
      e.g. Wiskott-Aldrich Syndrome, Common Variable Immunodeficiency and Hyper-IgM
      Syndrome. The common denominator is a dysregulation of immune responses affecting
      T and B cells with central and/or peripheral tolerance mechanisms being
      disturbed. Autoimmunity and autoinflammation may also occur in atypical
      phenotypes of combined immunodeficiencies (CID) usually associated with severe
      infectious complications. These unexpected presentations of classical CID are
      very instructive in how low numbers of T and B cells go hand in hand with skewing
      of lymphoid repertoires and function. The resulting immune dysregulation may lead
      to self-reactivity with organ damage and malignancy.

PMID- 20146942
TI  - Vitamin D and autoimmune rheumatologic disorders.
AB  - Vitamin D levels depend on many variables, including sun exposure, age,
      ethnicity, body mass index, use of medications and supplements. A much higher
      oral vitamin D intake than the current guidelines is necessary to maintain
      adequate circulating 25(OH)D levels in the absence of UVB radiation of the skin.
      In addition to the traditional known metabolic activities, vitamin D has been
      shown to modulate the immune system, and its deficiency has been linked to the
      development of several autoimmune disorders including type 1 diabetes and
      multiple sclerosis. Experimental use of vitamin D has revealed a novel role in
      the immunopathogenesis of autoimmune diseases. Disorders such as systemic lupus
      erythematosus, rheumatoid arthritis, Behcet's, polymyositis/dermatomyositis and
      systemic scleroderma have all been associated to some extent to vitamin D
      deficiency. If vitamin D deficiency occurs at a higher rate in patients with
      autoimmune disorders, then appropriate supplementation may be indicated.

PMID- 20146943
TI  - [The new look of Revue des Maladies Respiratoires].

PMID- 20146944
TI  - [2010: world year of the lung].

PMID- 20146945
TI  - [Why is pulmonary rehabilitation so underused? How can this situation be
      improved?].

PMID- 20146946
TI  - [Pulmonary hypertension of the elderly: not so infrequent].

PMID- 20146947
TI  - [COPD routine management in France: are guidelines used in clinical practice?].
AB  - INTRODUCTION: COPD management guidelines have been proposed to improve the major
      outcomes for COPD patients. In clinical practice, COPD treatment is only
      partially consistent with current guidelines and recommendations. OBJECTIVE:
      Global initiative for chronic obstructive lung disease (GOLD) guidelines are
      based on a COPD severity scale and are subject to change as the evidence based
      evolves. The main purpose of our study was to access whether the treatments
      prescribed to patients with COPD were consistent with these guidelines. METHODS:
      Treatments prescribed by French physicians to 542 patients with COPD in stable
      conditions were recorded according to the severity of obstruction, using GOLD
      classification. We compared our prescription data base with the GOLD guidelines.
      RESULTS: Forty percent of the initial physicians were chest specialists.
      PATIENTS: 78.3 % men, (64.8+/-10.8years) and 25 % were still smokers at
      inclusion. We found an important discrepancy between recommended treatment and
      COPD severity. Bronchodilators were commonly prescribed, but 11 % in severe COPD
      (stages III and IV) did not receive them. Inhaled steroids (ICS) were used
      respectively in 55.2 %, 59.4 % of patients in stages I, II (FEV1>50 %) (for whom
      they are not recommended) and 77.4 and 85.3 % in stages III and IV. Only 30 % of
      patients used ICS+beta2 agonists in the same device. Influenza vaccination had
      been performed in only half of patients whatever the severity of COPD. Pulmonary
      rehabilitation had been used by 10 % of patients, (stage II: 6.4 %, stage III:
      9.6 %, stage IV: 20.6 %). CONCLUSIONS: We confirmed that there are discrepancies
      between COPD guidelines and routine treatments. Some treatments such as ICS were
      overused in mild phenotypes, whereas in a high proportion of cases influenza
      immunisation and rehabilitation were omitted.

PMID- 20146948
TI  - [Characteristics and management of acute exacerbations of COPD in hospital.
      EABPCO-CPHG study by the college of general hospital respiratory physicians].
AB  - INTRODUCTION: A cohort was formed to explore the evolution of COPD patients
      treated in general hospitals for acute exacerbations (AE). The present article
      describes and compares patient characteristics according to whether COPD was
      diagnosed before the AE or not. METHODS: Data were analyzed for 1,824 patients
      admitted between October 2006 and June 2007 to 68 departments of respiratory
      medicine. RESULTS: Population characteristics were: male, 77%; mean age, 70.3+/
      11.3 years; current smokers, 33%; baseline grade 3-4 dyspnoea, 47%; FEV1<or=50%
      predicted, 63%. The 290 patients (15.9%) with AE preceding the diagnosis of COPD
      tended to be younger, female, smokers and had less severe baseline dyspnoea and
      airflow obstruction. Even so, 21% had grade 3-4 dyspnoea and 44% had FEV1<or=50%
      predicted. At the onset of the AE, they exhibited as many signs of severity and
      they required intensive care and assisted ventilation as often as the patients in
      whom the AE followed a diagnosis of COPD. CONCLUSION: When an AE precedes the
      diagnosis of COPD, the morbidity of the COPD and the AE is far from negligible,
      justifying efforts to achieve an earlier diagnosis of COPD.

PMID- 20146949
TI  - [Pulmonary arterial hypertension in the elderly subject].
AB  - OBJECTIVE: To describe the features of pulmonary arterial hypertension (PAH) in
      elderly patients. METHODS: A single centre, descriptive study of PAH patients
      consecutively referred to a regional centre, from September 2002 to February,
      1st, 2009. The group of patients aged 65 and above at the time of the diagnosis
      was compared to the younger patients. RESULTS: Sixty-six patients suffering from
      PAH (group 1) have been investigated by means of right heart catheterisation.
      There were 24 patients aged 65 and above. Mean pulmonary arterial pressure was
      lower in the patients aged over 65. The older patient group had more respiratory
      and/or cardiac co-morbidities, a lower median distance in the 6minute walk test
      and a higher median Pro-BNP level. Specific PAH treatments were prescribed in
      both groups. Fifteen patients aged 65 and above were on long-term oxygen therapy
      (vs four younger patients, p<0.0001). The elderly patients had a median survival
      of 32 months. CONCLUSION: The diagnosis of PAH in elderly patients is associated
      with a poor prognosis. The management of these patients needs further studies.

PMID- 20146950
TI  - [Anaesthesia for bronchial echoendoscopy: experience with the laryngeal mask].
AB  - INTRODUCTION: Endobronchial ultrasound guided transbronchial needle aspiration
      (EBUS-TBNA) has recently been shown to be an accurate modality in the diagnosis
      and staging of mediastinal lymph node metastases. This procedure takes
      significantly longer than a conventional bronchoscopy and may therefore cause
      more discomfort. Since its introduction into respiratory practice in France,
      several airway management strategies have been used. PATIENTS AND METHODS: Both
      anaesthesia care and procedural sedation services share the goals of providing
      the patient with comfort during a potentially distressing procedure while also
      ensuring that the operating physician has an acceptable working environment.
      Historically, anaesthesiologists have applied the expertise gained in managing
      anaesthesia for major surgery to sedation care for minor procedures. While the
      supply of anaesthesiologists and anaesthetists has shown only a modest increase,
      the growth in minimally invasive procedures has been exponential in recent years.
      To investigate this further, we performed a retrospective study of the use of
      general anaesthetic with ventilation by a laryngeal mask during EBUS, which we
      have adopted in our unit. RESULTS: Sixty-three patients were included in the
      study. In 41 a laryngeal mask was used and in 22 the examination was performed
      under local anaesthetic alone. Eighty-seven percent of procedures were
      informative with cells from lymph nodes obtained (89% from examinations using
      laryngeal mask with a mean of 3.8 passes and 86% with sedation alone with a mean
      of 2.9 passes). In 45 cases (78%) it was possible to avoid mediastinoscopy.
      CONCLUSION: It was possible to establish a secure airway and maintain oxygenation
      with the laryngeal mask during bronchoscopy without any reduction in the success
      of the procedure.

PMID- 20146951
TI  - [The role of lung volume measurements by plethysmography in the follow-up of
      asthma in children].
AB  - In asthmatic children, control of the disease is perfect when no symptoms occur
      and lung function is normal. The aim of this study is to analyse the role of
      plethysmography in the follow-up of asthmatic children. We present the results of
      a retrospective study of lung function (plethysmography and forced expiratory
      flow) in about 100 asthmatic children aged five to 16years. FEV1/FVC less than
      80% predicted was considered as pathological (airflow obstruction). The ratio
      RV/TLC was considered pathological if greater than 30% and RV was considered
      pathological if greater than 120% (lung hyperinflation). Bronchodilator
      reversibility was performed in all patients. All patients were studied in a
      stable condition. None had developed any asthmatic exacerbations during the past
      month. We found a significant correlation between the residual volume/total lung
      capacity (RV/TLC) ratio and, on one hand: FEV1 (p<0.0001, R=-0.374), and on the
      other hand FEV1/FVC (p=0.07, R=-0.182) or forced expiratory flow 25-75 (p=0.03,
      R=-0.216). When comparing children with (n=40) and without (n=60) lung
      hyperinflation, we noticed more diurnal symptoms (30/40 vs 10/60, p=0.05), lower
      weight (33.9kg vs 41.8kg, p<0.05) and lower body mass index (16.9kg/m(2) vs
      18.4kg/m(2), p<0.01). Among the children with defined airway obstruction, 49%
      also had lung hyperinflation. Twenty-three children had normal forced expiratory
      ratios but an increase of the ratio RV/TLC or of RV. When compared with children
      without lung hyperinflation, the age at diagnosis was significantly lower (3.9+/
      1.9years vs 6.2+/-3.1years, p<0.01) and weight slightly lower (31+/-10kg vs 40+/
      11kg, p=0.04). In conclusion, the use of plethysmography and thus the evaluation
      of pulmonary hyperinflation contributed to a better appreciation of the asthmatic
      phenotype in children.

PMID- 20146952
TI  - [Determinants of geographic variations in asthma medication in Quebec].
AB  - BACKGROUND: The study of geographic variations in the use of medication can
      constitute an interesting and useful option in public health surveillance for the
      identification of population needs and for the fair partition of resources. Many
      studies report variations in the use of medication that are not always
      understood. Considering the importance of medication, particularly for chronic
      diseases like asthma, it is important to identify factors that can explain
      geographic differences in the utilization of medications in order to determine
      optimal prescription practices. METHODS: We used a multilevel analysis to explore
      determinants of variation among welfare recipients and subscribers covered by the
      Quebec public drug plan, aged five to 44, who claimed at least one prescription
      for an asthmatic medication in 2003. The analysis was based on 73 small areas in
      Quebec's 15 health regions. RESULTS: Prevalence of usage and hospitalization
      rates are the main predictors of variation in medication intensity. On the other
      hand, prevalence of usage is related to the area of residence, proportion of
      welfare recipients and prevalence of smokers. The quality of medication is
      related to practitioners' specialty. CONCLUSION: Different factors contribute to
      the understanding of geographic variations in asthma medication but it remains
      important to control for severity. Small area analysis makes it possible to
      identify specific areas facing more important problems in the prevalence and use
      of medication for asthma and thus leads to better understanding of local needs
      for more targeted interventions.

PMID- 20146953
TI  - [Severe haemoptysis revealing a Rasmussen aneurysm].
AB  - INTRODUCTION: The incidence of pulmonary tuberculosis is actually increasing. In
      active tuberculosis, an aneurysm of the pulmonary artery represents a frequent
      cause of haemoptysis. In cases of tuberculosis sequelae, the origin of the
      haemoptysis is often a bronchial artery. CASE REPORT: We describe the case of a
      man from Morocco who presented with severe haemoptysis. He was cachectic, had a
      fever and his chest X-ray showed a cavity in the left lower lobe. CT angiography
      (MDCTA) showed a Rasmussen aneurysm of the pulmonary artery. This was occluded
      with coils, and multi-drug therapy against Mycobacterium tuberculosis was
      initiated as soon as tuberculosis was diagnosed. Two months later, there was no
      recurrence of the haemoptysis and repeat the MDCTA showed no opacification of the
      aneurysm. CONCLUSIONS: In patients with severe haemoptysis and evidence of active
      pulmonary tuberculosis, MDCTA may allow correct identification of the bleeding
      origin. In our case, the management of the pulmonary aneurysm relied upon
      pulmonary artery vasoocclusion. This treatment allowed us to wait for the
      antituberculosis treatment to be effective and reduces the need for a thoracic
      surgery.

PMID- 20146954
TI  - [Exsudative pleurisy revealing an infected aneurysm of the abdominal aorta].
AB  - INTRODUCTION: The development of a sero-sanguinous pleural effusion is a rare,
      often overlooked, manifestation of a ruptured infected aneurysm of the abdominal
      aorta. CASE REPORT: A man of 84years was referred for management of a left-sided
      pleural effusion associated with symptoms of infection. He had presented two
      months previously with methicillin resistant staphylococcal septicaemia, the
      origin of which was a plantar ulcer. The patient was apyrexial and had no
      abdominal pain. A thoraco-abdominal CT scan without contrast showed a peri-aortic
      abdominal mass suggesting a tumour. A contrast enhanced scan and peri-aneurysmal
      aspiration showed that it was an infected aneurysm of the abdominal aorta that
      had ruptured into the left pleural cavity. The progress was unfavourable despite
      double antibiotic therapy. CONCLUSION: In the face of a sero-sanguinous pleurisy,
      particularly if associated with unexplained symptoms of infection, a search
      should be made for an abdominal aortic aneurysm. Surgical treatment of the
      aneurysm should be undertaken if the general condition of the patient and the
      localisation and morphology of the aneurysm permit.

PMID- 20146955
TI  - [Isolated abscess of the thoracic and abdominal wall: an exceptional form of
      tuberculosis].
AB  - Isolated thoracic parietal involvement is a very rare form of tuberculosis and
      multifocal localization is exceptional. It often poses a diagnostic problem with
      parietal tumours requiring recourse to surgical biopsy. We report a case of
      tuberculous abscess localized to the anterior and superior part of the chest wall
      with a second abdominal localization but without any pulmonary involvement. The
      patient was a woman of 56 years presenting with a one-year history of a swelling
      to the right of the sternum accompanied after several months by a second swelling
      to the right side of the abdomen. The radiological and biological investigations
      revealed a parietal tumour in two separate areas. The diagnosis was confirmed by
      histological examination of a surgical biopsy and bacteriological examination of
      a percutaneous aspirate of the collection. Standard anti-tuberculosis treatment
      was given for nine months with good clinical and radiological resolution. In this
      case report, we study the anatomical and clinical features of this condition and
      discuss the diagnostic difficulties.

PMID- 20146956
TI  - [Nocardia farcinica infection in a patient with cystic fibrosis].
AB  - Infections by Nocardia species are uncommon and generally affect
      immunocompromised patients. This bacteria has rarely been isolated from cystic
      fibrosis patients (CF), especially those who are not taking oral corticosteroids.
      We report a case of a patient with CF harbouring Nocardia farcinica. An 18-year
      old male diagnosed with CF at the age of eight (F508 del/G85E) had been treated
      for allergic bronchopulmonary aspergillosis in 1998 with itraconazole, and a
      first colonization with Pseudomonas aeruginosa was eradicated in 2003. From May
      2006, he presented with recurrent left- and right-sided pneumothorax. In June
      2006, he presented with dyspnoea, fever, and nodular eruption on his ankles.
      Chest X-ray and CT scan revealed a right pneumothorax, severe bronchiectasis and
      bilateral alveolar consolidation. N. farcinica was idolated from his sputum
      without any other pathogens. Treatment with intravenous cotrimoxazole associated
      with imipenem and amikacin was initiated for three weeks followed by oral
      cotrimoxazole for a further nine months. The patient's symptoms and alveolar
      consolidation on CT scan improved. During 2007, his respiratory condition
      worsened and his FEV(1) declined from 50 to 26 % predicted. His pneumothorax
      recurred. He had chronic colonization with P. aeruginosa and was on the list for
      lung transplantation. Nocardia, a Gram positive bacillus, causes mainly pulmonary
      infection, usually in the context of immune suppression. The most frequent
      species is N. asteroides. In CF, very few cases have been reported; almost always
      N. asteroides, but exceptionally N. farcinica. In CF patients with worsening
      pulmonary condition, Nocardia should be considered, as well as other unusual
      pathogens.

PMID- 20146957
TI  - [A rare cause of cyanosis: Sulphaemoglobinaemia related to thiocolchicoside
      (Miorel)].
AB  - INTRODUCTION: An acquired abnormality of haemoglobin is among the many causes of
      cyanosis, especially in patients with no identified cardiorespiratory cause. CASE
      REPORT: A 50-year-old woman, suffering from amyotrophic lateral sclerosis, was
      hospitalised for dyspnoea. Physical examination revealed cyanosis that persisted
      despite oxygen therapy. Discordance between the reduced arterial oxygen
      saturation and normal arterial oxygen tension led to a search for a
      dyshaemoglobinaemia as a possible cause. Use of co-oxymetry with
      spectrophotometry revealed sulphaemoglobinaemia. Sulphaemoglobinaemia is due to
      irreversible incorporation of a thiol radical into the porphyrin ring of a haem
      group. This decreases the affinity of haemoglobin for oxygen and thus reduces
      oxygen carrying capacity. A drug-induced cause is often identified. However, no
      previously described cause for sulphaemoglobinaemia was identified in our
      patient. The patient was currently being treated with thiocolchicoside
      (Miorel((R))). Thiocolchicoside was suspected as the cause because its chemical
      structure contains an easily hydrolysable thiol radical. Withdrawal of
      thiocolchicoside led to regression of the sulphaemoglobinaemia. CONCLUSIONS: This
      report underlines the importance of searching for an acquired abnormality of
      haemoglobin (methaemoglobinaemia or sulphaemoglobinaemia) in patients with
      cyanosis resistant to oxygen, in the absence of any cardiorespiratory
      abnormality. This case is the first to suspect thiocolchicoside as a possible
      cause of sulphaemoglobinaemia.

PMID- 20146958
TI  - [Obliterative bronchiolitis with organising pneumonia following FOLFOX 4
      chemotherapy].
AB  - INTRODUCTION: FOLFOX 4 chemotherapy (5-fluorouracil, leucovorin and oxaliplatin)
      is the standard adjuvant treatment for stage III colon cancer. The principal
      secondary effects described are haematological, gastro-intestinal or
      neurological. A single case of obliterative bronchiolitis with organising
      pneumonia has been described recently. CASE REPORT: We report the case of a
      female patient aged 74 years who, after 12 courses of FOLFOX 4 chemotherapy,
      developed acute onset of severe shortness of breath and a dry cough but remained
      afebrile. A thoracic CT-scan showed symmetrical bilateral interstitial
      infiltration that was reticular in appearance, and predominantly basal and
      peripheral in distribution. Broncho-alveolar lavage revealed an alveolitis with
      9% eosinophils and 4% neutrophils. Transbronchial biopsies showed the appearances
      of obliterative bronchiolitis with organising pneumonia. Systemic corticosteroid
      treatment led to a remarkable clinical and functional improvement. CONCLUSION: To
      our knowledge, this is the second case of obliterative bronchiolitis with
      organising pneumonia that has been described following adjuvant treatment based
      on FOLFOX 4.

PMID- 20146959
TI  - [Pulmonary malignant melanoma: primary or metastatic?].
AB  - Primary pulmonary malignant melanoma is rare (0.01% of pulmonary cancers); only
      25 cases are published in the literature. The diagnosis of primary pulmonary
      malignant melanoma is controversial, the pathogenesis is unknown and a pulmonary
      metastasis from a mucocutaneous melanoma is the main differential diagnosis. The
      diagnosis is based on the strict application of the Jensen criteria published in
      1967. We report the case of an asymptomatic 82-year-old man presenting with a
      fortuitously discovered primary pulmonary malignant melanoma according to the
      Jensen criteria and treated by lobectomy (cT1N0M0). Surgery seems to be the gold
      standard treatment on account of the poor sensitivity of melanoma to chemotherapy
      and radiotherapy. Surgical resection and the absence of nodal involvement suggest
      a good prognosis even though the small number of cases does not produce useful
      statistical data. This observation raises the question of (18)FDG CT-PET in this
      situation, particularly of the whole body, by extrapolation from the
      recommendations in mucocutaneous melanoma. The lack of increased uptake on
      (18)FDG CT-PET could be a new paraclinical diagnostic criterion to add to the
      clinical criteria of Jensen. This report is the first, which shows the results of
      (18)FDG CT-PET (standard and whole-body) under this situation.

PMID- 20146960
TI  - [Assessment of prognostic factors of thoracic synovial sarcoma].
AB  - INTRODUCTION: Synovial sarcoma is an uncommon tumour and thoracic involvement is
      rare and of varying location. Clinical characteristics are dominated by pain,
      with a slow progression over years. Pathological and immuno-histochemical
      characteristics are helpful in the diagnosis but a specific translocation between
      chromosomes X and 18 is crucial for confirmation. Extensive surgical resection is
      required for cure, combined with adjuvant radiotherapy in the presence of adverse
      prognostic factors. CASE REPORT: We report a case of synovial sarcoma of the
      chest wall, responsible for chronic local pain for several years, presenting as
      an acute pleuropneumonitis in a 21-year-old patient. In view of the large size of
      the tumour, associated with a high proliferation index (Ki-67), a surgical
      resection was performed, together with local adjuvant radiotherapy. CONCLUSION:
      This case report reviews synovial sarcoma and underlines the difficulties and
      requirements of both diagnostic strategy and therapeutic management. Among them,
      an initial systematic review of prognostic factors (tumour size, mitotic
      activity, proliferation index, SYT-SSX type fusion, histological grade) is
      crucial to determine the therapeutic options.

PMID- 20146962
TI  - [Abstracts of the 14th French-speaking Pneumology Congress, Marseille, France,
      2010].

PMID- 20146961
TI  - [Nail clubbing and lung hydatid cysts].

PMID- 20146963
TI  - Urban area disadvantage and under-5 mortality in Nigeria: the effect of rapid
      urbanization.
AB  - BACKGROUND: Living in socioeconomically disadvantaged areas is associated with
      increased -childhood mortality risks. As city living becomes the predominant
      social context in low- and middle-income countries, the resulting rapid
      urbanization together with the poor economic circumstances of these countries
      greatly increases the risks of mortality for children < 5 years of age (under-5
      mortality). OBJECTIVE: In this study we examined the trends in urban population
      growth and urban under-5 mortality between 1983 and 2003 in Nigeria. We assessed
      whether urban area socioeconomic dis-advantage has an impact on under-5
      mortality. METHODS: Urban under-5 mortality rates were directly estimated from
      the 1990, 1999, and 2003 Nigeria Demographic and Health Surveys. Multilevel
      logistic regression analysis was performed on data for 2,118 children nested
      within data for 1,350 mothers, who were in turn nested within data for 165
      communities. RESULTS: Urban under-5 mortality increased as urban population
      steadily increased between 1983 and 2003. Urban area disadvantage was
      significantly associated with under-5 mortality after adjusting for individual
      child- and mother-level demographic and socioeconomic characteristics.
      CONCLUSIONS: Significant relative risks of under-5 deaths at both individual and
      community levels underscore the need for interventions tailored toward community-
      and individual-level interventions. We stress the need for further studies on
      community-level determinants of under-5 mortality in disadvantaged urban areas.

PMID- 20146964
TI  - Perfluorinated compounds, polychlorinated biphenyls, and organochlorine pesticide
      contamination in composite food samples from Dallas, Texas, USA.
AB  - OBJECTIVES: The objective of this article is to extend our previous studies of
      persistent organic pollutant (POP) contamination of U.S. food by measuring
      perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated
      biphenyls (PCBs) in composite food samples. This study is part of a larger study
      reported in two articles, the other of which reports levels of polybrominated
      diphenyl ethers and hexabromocyclododecane brominated flame retardants in these
      composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and
      hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health
      Perspect 118:357-362]. METHODS: In this study we measured concentrations of 32
      organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31
      different types of food (310 individual food samples) purchased from supermarkets
      in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated
      for an average American. RESULTS: Contamination varied greatly among chemical and
      food types. The highest level of pesticide contamination was from the
      dichlorodiphenyltrichloroethane (DDT) metabolite p,p 
      dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in
      whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28,
      52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon
      (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected
      perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in
      potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT
      metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest
      levels. CONCLUSION: Despite product bans, we found POPs in U.S. food, and
      mixtures of these chemicals are consumed by the American public at varying
      levels. This suggests the need to expand testing of food for chemical
      contaminants.

PMID- 20146965
TI  - Usefulness of an educational leaflet to modify sexual risk behaviour in women
      with external genital warts.
AB  - We aimed to assess the effectiveness of an educational leaflet to modify sexual
      risk behaviour in women with external genital warts. Women with genital warts who
      attended in daily gynecological practice participated in a 12-month prospective
      randomised observational study. Randomisation was carried out by centres. At the
      initial visit, patients underwent complete gynecological examination, including
      an acetic acid test. Those assigned to the intervention group received an
      educational leaflet to improve patient's knowledge about warts (counselled
      group). Only patients with complete clearance after 6 months of initial therapy
      continued the study. The counselled group included 114 women and the non
      counselled group 97. A significant increase in the use of condoms at visit 3 as
      compared with baseline (83.2% vs 66.1%, P < 0.05) was observed in the counselled
      group. The mean number of sexual partners was also significantly lower in the
      counselled group at each follow-up visit. Recurrences were documented in 9 of the
      145 patients who completed the study (recurrence rate 6.2%). Recurrences occurred
      in 7 patients in the counselled group and in 2 in the non-counselled group (8.6%
      vs 3.1%, P = 0.299), and in all cases occurred at 9 months after initiation of
      treatment. In conclusion, the educational leaflet, which is simple and easy to
      implement in routine daily practice, proved to be effective in modifying sexual
      risk behaviour in women with external genital warts. This educational strategy
      did not seem to affect recurrence if an acetic acid test is routinely performed
      during the initial work-up studies.

PMID- 20146966
TI  - Therapeutic drug monitoring of mycophenolic acid in patients with psoriasis.
AB  - Mycophenolate mofetil (MMF) has been shown to be effective in the treatment of
      psoriasis. MMF is the morpholinoethyl ester of mycophenolic acid (MPA), the
      active compound. Our objective was to characterize the pharmacokinetic profile of
      MPA in patients with psoriasis treated with MMF and to examine its correlation
      with effectiveness and toxicity. Eleven patients with moderate-to-severe chronic
      plaque psoriasis were treated with oral MMF 30 mg kg-1 daily over a period of 16
      weeks. Patients were reviewed at 3, 8 and 16 weeks, checking the Psoriasis Area
      and Severity Index (PASI) and possible adverse events, and performing MPA C0
      (trough) and C1 (1-hour post-dose) plasma levels. The reduction in PASI was
      statistically significant in all our patients. The drug was well tolerated. There
      was no significant correlation between C0 and C1 MPA levels and the reduction of
      PASI, improvement rates of PASI from baseline, weight of the patients and total
      dosage of MMF. Nevertheless, the highest detected mean levels of MPA C1 were
      observed in two of the patients with the highest improvement rate of PASI at the
      end of the study. Although C1 levels do not seem to strongly correlate with the
      effectiveness of the drug, the finding that the highest detected mean levels of
      MPA C1 were observed in two of the patients with the highest improvement rate of
      PASI suggests that the monitoring of C1 could be useful in some individual cases.

PMID- 20146967
TI  - Bilateral granuloma annulare of the external ear.

PMID- 20146968
TI  - Cutaneous Abrikossoff's tumour in coexistence with congenital deaf-mutism.

PMID- 20146969
TI  - Successful thalidomide treatment of adult solitary perianal Langerhans cell
      histiocytosis.

PMID- 20146970
TI  - Comments on: Papuloerythroderma of Ofuji associated with chronic lymphatic
      leukaemia (Eur J Dermatol 2009; 19(4): 396-7).

PMID- 20146971
TI  - Nosocomial disseminated Mycobacterium chelonae infection in an immunocompromised
      patient.

PMID- 20146972
TI  - [Editorial of the President of the SFBC].

PMID- 20146973
TI  - [Accreditation of French labs: contribution of the SFBC].

PMID- 20146974
TI  - [Current issues in measurement and reporting of urinary albumin excretion].
AB  - Urinary excretion of albumin indicates kidney damage and is recognized as a risk
      factor for progression of kidney disease and cardiovascular disease. The role of
      urinary albumin measurements has focused attention on the clinical need for
      accurate and clearly reported results. The National Kidney Disease Education
      Program and the IFCC convened a conference to assess the current state of
      preanalytical, analytical, and postanalytical issues affecting urine albumin
      measurements and to identify areas needing improvement. The chemistry of albumin
      in urine is incompletely understood. Current guidelines recommend the use of the
      albumin/creatinine ratio (ACR) as a surrogate for the erro-prone collection of
      timed urine samples. Although ACR results are affected by patient preparation and
      time of day of sample collection, neither is standardized. Considerable
      intermethod differences has been reported for both albumin and creatinine
      measurement, but trueness is unknown because there are no reference measurement
      procedures for albumin and no referance materials for either analyte in urine.
      The recommanded reference intervals for the ACR do not take into account the
      large intergroup differences in creatinine excretion (e.g., related to
      differences in age, sex, and ethicity) nor the continuous increase in risk
      related to albumin excretion. Clinical needs have been identified for
      standardization of (a) urine collection methodes, (b) urine albumin and
      creatinine measurements based on a complete reference system, (c) reporting of
      test results, and (d) reference intervals for the ACR.

PMID- 20146975
TI  - [Dihydropyrimidine dehydrogenase deficiency and toxicity to fluoropyrimidine].
AB  - Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism
      of fluoropyrimidines, such as 5-Fluorouracil and its oral prodrugs derivatives,
      including capecitabine and ftorafur (UFT, S1). Numerous genetic mutations have
      been identified in the DPD gene locus (DPYD), with a few variants having
      functional consequences on enzymatic activity. The allele frequency is 5% for
      heterozygoty and is 0.2% for homozygoty. It is correlated to the frequency of DPD
      activity deficiency that has been frequently reported to cause early severe,
      sometimes lethal fluoropyrimidine-related adverse events, regardless of the drug.
      Taking in account the wide and frequent use of fluoropyrimidines, both in
      advanced and adjuvant settings, it is clearly a problem of public healthcare that
      cannot be underestimated. We review in the present article the performances of
      assays that assess DPD and DPYD status, with an emphasis on their respective
      robustness and suitability for routine clinical applications. We show that DPD
      deficiency can be already detected primarily to treatment in practice and this
      detection could avoid life-threatening fluoropyrimidines toxic-side effects.

PMID- 20146976
TI  - [Prognostic value of S-100B protein plasma measurement after cardiac arrest].
AB  - S-100B protein is selectively synthesized by glial cells, and is released in
      biological fluids after acute brain damage. We analyzed initial levels and
      evolution of plasma S-100B protein concentrations after resuscitated
      cardiopulmonary arrest (CPA). S-100B levels were determined in 27 subjects at the
      time of CPA (H0) then 12, 24 and 48 h after resuscitation. Initial levels of S
      100B and kinetics revealed that: 1) 95% the of subjects with a concentration of
      protein S-100B greater than 0.80 microg/L at H0 did not survive; 2) 62% of
      subjects with a concentration of protein S-100B lower than 0.80 microg/L at H0
      survived; 3) 100% of subjects with a protein S-100B level lower than 0.80
      microg/L at H0 and whose evolution kinetics of S-100B levels showed a decrease
      survived; 4) 100% of the subjects whose S-100B levels increased from H12 died. In
      summary, this study suggests that the threshold of 0.80 microg/L for S-100B
      plasma levels at H0 could be predictive for the outcome of the CPA, when
      associated with the kinetic study of S-100B plasma concentration.

PMID- 20146977
TI  - [Gallstone biochemical characteristics using Fourier transform infrared
      spectroscopy method].
AB  - This study reports biochemical composition and morphological aspect of gallstones
      as investigated by spectroscopy IR method. Participants were 24 patients composed
      of 12 males and 12 females who underwent cholecystectomy with age mean of 44.8
      years. The gallstones were classified either as pigments stones (n = 12),
      cholesterol stones (n = 8) or as mixed stones (n = 4) according to analysis by
      Fourier transform infrared spectroscopy. The infrared spectroscopy quantification
      reported eight stones contained 100% of cholesterol, eight of 100% of calcium
      bilirubinate, four stones were composed of 65% calcium bilirubinate phosphate and
      35% calcium carbonate, and four stones contained 65% cholesterol, 30% neutral
      calcium bilirubinate, 5% protein and traces of calcium bilirubinate acid. Our
      findings showed that most gallstones were composed of pigment stones with
      relative large proportion of cholesterol stones, whereas previous study in
      Caucasian reported predominance of cholesterol stones. These findings indicate
      the influence of diet and chronic haemolysis in the stones formation in regard to
      biochemical composition differences between those found in European area and our
      results. Therefore, Fourier transform infrared spectroscopy method allowed to
      determine quality and quantity of biochemical components of gallstones.
      Therefore, a careful survey must allow knowing the nutritional and environmental
      factors in the occurrence of gallstones to Cote d'Ivoire, in order to prevent
      this disease.

PMID- 20146978
TI  - [Evaluation of an automated assay of thyrotropin receptor antibody (TRAb) on
      Elecsys Analyser 2010].
AB  - 2nd generation assays are currently available to determine the concentration of
      thyrotropin receptor antibody (TRAb) present in Graves' disease. The aim of this
      study was to evaluate the analytical performance of TRAb assay on Elecsys 2010
      and Cobas(R)e of Roche Diagnostics, a new test using electrochemiluminescence
      immunoassay (ECLIA). The analytical performance observed with this assay is
      accurate (repetability and reproductibility, analytical and functional
      sensitivities). Comparing this method with Brahms' assay (TRAK human RIA), the
      correlation observed can be put in the equation: y = 1.013 x + 1.381; r = 0.92.
      With a positive value in ECLIA at 0.9 UI/L and at 1 UI/L in RIA (functional
      sensitivity fixed by manufacturers), concordance study shows a false negative and
      two false positive. With a positive value at 0.8 UI/L with ECLIA (functional
      sensitivity calculated from precision's profile for a CV inferior to 10%), there
      is no false negative and two false-positive results, this value seems to give a
      better sensitivity.

PMID- 20146979
TI  - [Peritonitis due to glycopeptides-resistant Staphylococcus epidermidis].
AB  - A 71 years old male patient with a history of hypertension for more than 20
      years, with chronic kidney failure under intra-peritoneal (IP) dialysis since
      June 2004, presents in March 2008 with glycopeptides-resistant Staphylococcus
      epidermidis peritonitis. Under vancomycin IP (alone or in association), clinical
      symptoms do not entirely subside and bacteria as well as white blood cells do
      persist in the peritoneal dialysis fluid. Under rifampicin IP, all clinical and
      laboratory abnormalities disappear. All 4 isolates of S. epidermidis obtained in
      the laboratory during this infectious episode appear to be susceptible to
      glycopeptides by the disk diffusion method, but MICs measurements confirm
      resistance. The only (blood) concentration of vancomycin measured during this
      episode does neither allow us to affirm, nor to exclude, that sub-inhibitory
      concentrations of vancomycin facilitated resistance to glycopeptides. This case
      report raises the question of the optimal follow-up of those patients with
      residual kidney function: when, how often, and how do we need to measure blood
      vancomycin?

PMID- 20146980
TI  - [Complications of infected aneurysm due to Salmonella enteritidis: a case
      report].
AB  - Salmonelloses are becoming more frequented. To date, very few cases of aneurisms
      or vascular grafts infections have been described. We report the rare case of an
      extradigestive manifestation, due to Salmonella enteritidis affecting a patient
      with Behcet disease. The biological diagnosis is based on microorganism isolation
      from the site of infection but also from blood cultures. The initial treatment
      combined antibiotherapy and surgical procedure and replacement of the
      arteriovenous graft.

PMID- 20146981
TI  - [Contribution of CSF analysis to diagnosis and follow-up of tuberculous
      meningitis].
AB  - We report the case of a patient who was admitted to the hospital because of
      language and mental confusion. His initial lumbar puncture revealed 193
      leukocytes per mm3 mostly lymphocytes (95%), no red blood cells, high protein
      content (1.20 g/L) and normal glucose level. The antibiotic therapy by
      amoxicilline and aciclovir during 6 days led to complete clinical recovery in a
      week. A CT scan of the cerebrum showed no abnormalities, nor did chest
      radiography. Twelve days after discharge, the patient was rehospitalized because
      of a meningitis syndrome. On lumbar puncture, the CSF analysis revealed 280
      leukocytes/mm3, 56% lymphocytes, 10% monocytes and 34% polymorphonuclear cells.
      CSF chemistry showed a protein level of 3.54 g/L, and a glucose level depressed
      at 0.9 mmol/L. Because of the clinical symptoms and CSF abnormalities, the
      patient received aciclovir, amoxicilline vancomycine, isoniazide, rifampicine,
      pyrazinamide and ethambutol. Screening for infections gave negative results until
      the 37th day, when the diagnosis of tuberculous meningitis was confirmed by the
      isolation of Mycobacterium tuberculosis in the repetitive CSF. Antituberculous
      therapy was expanded. According the Reiber diagrams, intrathecal IgG synthesis
      was negative at day 25, day 37, month 4, month 9, month 17. Intrathecal IgM
      synthesis was elevated at day 12 and day 25 and intrathecal IgA synthesis at day
      25. Improvement of the patient's conditions by tuberculosis treatment was
      obtained in 17 months. Cerebrospinal fluid analysis has been the basis for the
      diagnosis and follow-up of tuberculous meningitidis.

PMID- 20146982
TI  - [Screening and diagnosis of gestational diabetes. Evaluation of the
      methodological quality of the guidelines of the Haute Autorite de Sante, of the
      American Diabetes Association, and of the World Health Organisation].
AB  - We critically appraised the methodological quality of the clinical practice
      guideline (CPG) published by the Haute autorite de sante (HAS) about screening
      and diagnosis of gestational diabetes, and we compared its quality with that of
      two other CPGs, i.e. that of the American diabetes association (ADA) and that of
      the World health organisation (WHO). According to the AGREE criteria, HAS and ADA
      have produced CPGs that have approximately got the same levels of quality. Both
      these CPGs obtain AGREE scores that are better than those of WHO. Although the
      CPG of the HAS suffers from a few methodological drawbacks, regarding more
      particularly stakeholder involvement (AGREE domain n degrees 2), applicability
      (AGREE domain n degrees 5) and editorial independence (AGREE domain n degrees 6),
      this CPG summarises, and allows to compare most, if not all, other CPGs available
      with each other, with their possible benefits or harms, which may be useful for
      professionals involved in the care of the patient.

PMID- 20146983
TI  - [The European Register of specialists in clinical chemistry and laboratory
      medicine: code of conduct Version 2-2008].

PMID- 20146984
TI  - Cytokines modulate neutrophil death.
AB  - Polymorphonuclear neutrophils (PMN) are terminally differentiated cells with a
      short life span, in the blood circulation. The prolongation of the life span of
      PMN is critical in their effectiveness against pathogens, in particular in the
      tissues. This review summarizes the effect of cytokines on PMN apoptosis and
      points to some examples of pathological situations characterized by inappropriate
      cytokine production associated with dysregulation of PMN apoptosis.

PMID- 20146985
TI  - Activation of innate host defense mechanisms by Borrelia.
AB  - Borrelia is the causative agent of Lyme disease, a widespread disease with
      important health consequences. Immune-mediated mechanisms are believed to play a
      major role in both host defense and in late complications of Lyme disease.
      Recognition of Borrelia and the initial activation of the innate immune system
      are important for host defense, as well as modulation of adaptive responses.
      Several classes of pattern recognition receptors (PRRs) have been suggested to be
      involved in the recognition of Borrelia: Toll-like receptors (TLRs), NOD-like
      receptors (NLRs) and C-type lectin receptors (CLRs). TLR2 has been found to be
      the most important receptor of the TLRs. The intracellular receptor NOD2, a
      member of the NLRs, might also play an important role in recognition. Mannose
      receptor is also involved in Borrelia recognition, but little is known about
      other CLRs such as dectin-1. After PRRs have recognized Borrelia, a signaling
      cascade is induced that leads to transcription of NF-kappaB, resulting in the
      production of pro-inflammatory cytokines. Understanding these pathways provides
      not only a better insight into the pathogenesis, but also provides potential,
      novel, therapeutic targets during active disease or post-infection complications.

PMID- 20146986
TI  - Prognostic value of inflammatory markers (notably cytokines and procalcitonin),
      nutritional assessment, and organ function in patients with sepsis.
AB  - OBJECTIVE: Procalcitonin is useful for the diagnosis of sepsis, but its
      prognostic value regarding mortality is unclear. Our objective was to determine
      the prognostic value of procalcitonin determined at the onset of sepsis, and to
      compare it with other markers of inflammatory response, malnutrition and organ
      dysfunction data. METHODS: We studied 253 hospitalized patients (146 men, 107
      women) with a median age of 65 years. Sepsis was defined as infection, and at
      least two SIRS criteria. We assessed co-morbidities, nutritional status,
      bacteremia, procalcitonin and other inflammatory markers (PCR, TNF-alpha, IL6,
      TREM-1, IL-10, IL-1ra, CD14 and LBP), and organ function using the SOFA score.
      Mortality was assessed at 28 days after onset of sepsis. RESULTS: At day 28, 49
      (19%) patients had died. Inflammatory markers showed only moderate predictive
      value for mortality, with IL-10 and IL-6 being the best predictors. Mortality was
      mainly related to organ dysfunction indicators (SOFA and Glasgow scores), serum
      lactate, ferritin and LDH levels, and to nutritional data such as subjective
      assessment, handgrip strength and serum transferrin levels. The most frequent
      location of sepsis was the lung, with 140 cases (55%), which showed more
      comorbidity, worse nutritional status, less frequent bacteremia and lower
      inflammatory response. When the analysis was limited to patients with non
      pulmonary sepsis, organ dysfunction, nutritional status and inflammatory markers
      showed the best prognostic value. Of the inflammatory markers, procalcitonin
      showed only moderate predictive value; however it showed the highest correlation
      with bacteremia and the ability to discriminate non-complicated sepsis from
      severe forms. CONCLUSION: Procalcitonin only showed moderate predictive value for
      sepsis-related mortality, being surpassed by organ dysfunction, nutritional
      status, IL-10 and IL-6. However, it proved useful to discriminate between non
      complicated and severe forms of sepsis.

PMID- 20146987
TI  - Human glioma tumors express high levels of the chemokine receptor CX3CR1.
AB  - The chemokine receptor CX3CR1 and its cognate ligand CX3CL1 (also known as
      fractalkine), are involved in central nervous system pathophysiology, in
      particular, in the cross-talk between neurons and microglia. It was therefore
      important to investigate the expression of CX3CR1 in gliomas, the most frequently
      occurring, malignant brain tumors. In a consecutive series of 70 patients with
      primary, central nervous glial tumors, CX3CR1 was highly expressed in tumor cells
      as assessed by RT-PCR mRNA and protein levels, and by immunohistochemistry, while
      the corresponding normal cells were negative. Receptor immuno-positivity did not
      correlate with histology, grade, chromosomal (1p,19q) deletion, or with
      methylation of the DNA repair gene promoter MGMT (O6-methylguanine-DNA
      methyltransferase). Thus, CX3CR1 expression is a frequent event in gliomas,
      irrespective of tumor classification and clinical severity. The molecular basis
      underlying CX3CR1 up-regulation and its functional biological significance remain
      to be determined.

PMID- 20146988
TI  - T cells co-producing Mycobacterium tuberculosis-specific type 1 cytokines for the
      diagnosis of latent tuberculosis.
AB  - Patients treated with tumor necrosis factor (TNF)-alpha-antagonizing medication
      are at increased risk of developing active tuberculosis (TB), brought about
      mainly by reactivation of latent infection. Thus, screening for latent TB
      infection (LTBI) prior to administration of anti-TNF-alpha-therapy is required.
      For a long time, the tuberculin skin test (TST) was the only means of diagnosing
      LTBI, however, interferon-gamma-release assays (IGRAs), are promising new tools.
      Fifty two patients with dermatological disorders were included prior to
      implementation of anti-TNF-alpha therapy. Mycobacterium tuberculosis (MTB)
      specific cytokine production, including interferon (IFN)-gamma, TNF-alpha,
      interleukin (IL)-2 and IL-10, was measured in CD4+ and CD8+ T cells by cytokine
      flow cytometry following stimulation of peripheral blood mononuclear cells (PBMC)
      with purified protein derivative (PPD) and early secretion antigenic target
      (ESAT)-6. Simultaneously, a TST was administered and 11 were TST-positive.
      Generally, MTB-specific IFN-gamma produced by CD4+ T cells correlated well with
      TST results. CD4+ T cells co-producing specific IFN-gamma and TNF-alpha after
      ESAT-6 stimulation showed the highest overall agreement with the TST (Kappa
      [kappa] = 0.87). Each single cytokine displayed individual patterns, the
      expression of IFN-gamma, however, showed the highest concordance with the TST
      (kappa = 0.82). This suggests that the enumeration of MTB-specific CD4+ T cells
      might introduce greater specificity for the diagnosis of latent TB, compared to
      the TST.

PMID- 20146989
TI  - Early pre-engraftment, functional, in vitro responsiveness of T lymphocytes in
      allotransplanted, acute leukemia patients: proliferation and release of a broad
      profile of cytokines, possibly predictive of graft-versus-host disease.
AB  - Previous studies of T cell reconstitution following allogeneic stem cell
      transplantation have described long-lasting T cell defects, including decreased
      levels of autocrine proliferating CD4+ T cells. However, T cell functions during
      the early phase of conditioning-induced, pre-engraftment pancytopenia have not
      been characterized previously. We used a whole blood assay to investigate T cell
      proliferation and cytokine release during the period of pre-engraftment
      cytopenia. The study included 13 acute leukemia patients receiving myeloablative
      conditioning followed by transplantation of G-CSF-mobilised peripheral blood stem
      cells derived from HLA-matched family donors. Maximal proliferation and cytokine
      release could not be reached by anti-CD3 stimulation alone, but was dependent on
      the presence of additional costimulation with anti-CD28. Circulating T cells
      showed a broad cytokine release profile after activation, and the highest levels
      were detected for IFNgamma, GM-CSF and IL-6. Correlation analyses showed that
      TNFalpha/IL-4/IL-5/IL-13 in particular were released as a separate cluster,
      IFNgamma and GM-CSF correlated strongly, whereas IL-17 showed a weak correlation
      to IL-6 only. The capacity of circulating T cells derived during pre-engraftment
      cytopenia to release high levels of IFNgamma, IL-6 and IL-17 in response to in
      vitro activation with anti-CD3+anti-CD28 showed statistically significant
      correlations with later acute GVHD. We conclude that allotransplanted patients
      have a functional T cell system even during the pre-engraftment period of severe
      pancytopenia.

PMID- 20146990
TI  - Inflammatory response in ventilated left and collapsed right lungs, serum and
      pleural fluid, in transthoracic esophagectomy for cancer.
AB  - INTRODUCTION: Open, right-sided, transthoracic esophagectomy with one-lung
      ventilation (OLV) triggers a massive inflammatory reaction. The influence of the
      OLV on the inflammatory cascade is unclear. Data on the inflammatory response in
      the ventilated left and collapsed right lung, respectively, are scarce. The aim
      of this study was to analyze this reaction in bronchoalveolar lavage (BAL) fluid
      from both lungs, the right pleural space and the peripheral blood, and to study
      its time course. METHODS: Concentrations of interleukin (IL)-6, IL-8, IL-10 and
      IL-1RA in the BAL fluids from the right and left lungs, respectively, in the
      peripheral blood and in the right pleural space in patients undergoing
      transthoracic esophagectomy for cancer, were determined using enzyme-linked
      immunosorbent assays in 29 patients. RESULTS: Assay of the pro-inflammatory
      cytokines in the bilateral BAL fluids showed significantly higher concentrations
      in the ventilated left lung at the time of extubation. The anti-inflammatory
      response was only seen with respect to IL-1RA, but not IL-10, and was mostly
      restricted to the ventilated left lung. In the blood, only IL-6, IL-10 and IL-1RA
      increased, whereas IL-8 showed little change. The response was already observed
      at the end of surgery, indicating a rapid reaction to the surgical and anesthetic
      trauma. In the pleural fluid, all cytokine concentrations increased, and the
      highest values were detected on day one post-surgery, and decreased thereafter.
      Pulmonary complications or anastomotic leakage were not related to the cytokine
      concentrations. CONCLUSION: Both the ventilated left and the collapsed right lung
      showed an inflammatory response. The response was more pronounced on the
      ventilated left side and the time courses were significantly different. In the
      blood, the pro-inflammatory IL-6 and both anti-inflammatory cytokines increased
      early on. All cytokines increased in the pleural cavity. The findings underline
      the complexity of the inflammatory reaction associated with OLV in transthoracic
      esophagectomy.

PMID- 20146991
TI  - Possible therapeutic effect of magnesium sulfate in pre-eclampsia by the down
      regulation of placental tumor necrosis factor-alpha secretion.
AB  - OBJECTIVE: To examine the effect of magnesium sulfate (MgSO(4)) on tumor necrosis
      factor-alpha (TNF-alpha) secretion by preeclamptic placentas. STUDY DESIGN:
      Cotyledons of six, term, normotensive and ten, pre-eclamptic placentas were
      dually perfused for six hours (6h), with MgSO(4) (6-7 mg %) in the maternal
      reservoir [normotensive (n = 3); pre-eclamptic (n = 5)], and with control medium
      (without MgSO(4)) [normotensive (n = 3); pre-eclamptic (n = 5)]. Perfusate
      samples from the maternal and the fetal circulations were collected every 30 min
      throughout the 6h of perfusion, and examined for TNF- alpha levels using ELISA.
      Statistical significance was determined using a 2-way analysis of variance.
      RESULTS: Pre-eclamptic placentas perfused with control medium (without MgSO(4))
      secreted higher levels of TNF-alpha into the fetal and the maternal circulations
      (1.60 +/- 0.59 pg/mL/g of cotyledon and 14.28 +/- 2.69 pg/mL/g of cotyledon,
      respectively), as compared to the fetal and maternal circulations of normotensive
      placentas (0.25 +/- 0.09 pg/mL/g of cotyledon and 6.73 +/- 1.11 pg/mL/g of
      cotyledon, respectively) (p < 0.01). Addition of MgSO(4) to normotensive
      placentas did not affect TNF-alpha levels in the fetal or maternal circulations.
      However, exposure of pre-eclamptic placentas to MgSO(4) significantly decreased
      TNF-alpha levels in both the fetal (0.89 +/- 0.09 pg/mL/g of cotyledon versus 1.6
      +/- 0.59 pg/mL/g of cotyledon; p < 0.05) and the maternal circulations (4.74 +/-
      2.78 pg/mL/g of cotyledon versus 14.28 +/- 2.69 pg/mL/g of cotyledon; p < 0.01).
      CONCLUSION: Down-regulation of placental TNF-alpha secretion by MgSO(4) in pre
      eclampsia might indicate a possible therapeutic effect for this agent in reducing
      maternal, endothelial dysfunction and in improving neonatal outcome in pre
      eclampsia, by reducing TNF-alpha levels in maternal and fetal circulations.

PMID- 20146992
TI  - Influence of significant weight loss on serum matrix metalloproteinase (MMP)-7
      levels.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their specific inhibitors
      (tissue inhibitor of metalloproteinases [TIMPs]), are involved in adipogenesis,
      angiogenesis and remodeling of extracellular matrix. MMPs and TIMPs have been
      shown to be associated with various diseases such as neurological disorders,
      malignancies and cardiovascular disease. MMPs and TIMPs are thought to play a
      major role in extensive reorganization of the adipose tissue in obesity. METHODS
      AND MATERIALS: To test whether significant weight loss alters circulating MMPs
      and TIMPs, 18 morbidly obese women, who underwent bariatric surgery for weight
      loss, were investigated before and one year after surgery in a prospective design
      study. Body composition, glucose and lipid metabolism parameters were determined
      in all study subjects before and after weight loss. Circulating MMP-2, -3, -7 and
      TIMP-1, -2 and -4 serum levels were measured using commercially available, enzyme
      linked immunoassays. RESULTS: Pronounced weight loss was accompanied by
      improvements in glucose homeostasis and lipid parameters. In the mean time MMP-2
      and MMP-3, as well as TIMP-1, -2 and TIMP-4 concentrations were not affected by
      significant weight loss, and circulating MMP-7 increased significantly after
      bariatric surgery, although without reaching the standard levels as determined in
      18, lean, healthy women. CONCLUSION: Our data indicate that reduced MMP-7 levels
      in obesity might be restored by significant weight loss, suggesting that the
      reorganization of adipose tissue in obesity might be partially reversible by
      weight reduction. We hypothesize that increased circulating MMP-7 might indicate
      enhanced adipocyte differentiation in subjects who had undergone bariatric
      surgery.

PMID- 20146993
TI  - Prolonged standard treatment for systemic lupus erythematosus fails to normalize
      the secretion of innate immunity-related chemokines.
AB  - The pathogenesis of systemic lupus erythematosus (SLE) is far from having been
      elucidated at the molecular level. Using a multiplex system, we profiled 18
      immune mediators in the plasma from 57 patients with SLE. Thirteen of them showed
      mild to moderate disease activity, and 29 showed severe activity, based upon the
      SLEDAI score. Fifteen patients were in complete clinical remission. Those
      patients with active disease, and those in clinical remission had been undergoing
      immunomodulatory treatment for an average of 10.7 months and 19.2 months
      respectively at the time of the visit. Samples obtained from 10 healthy
      volunteers were used as control. Patients with active disease and those with
      inactive disease showed elevated levels of the chemoattractant proteins MCP
      1/CCL2, MIP1-beta/CCL4 and IL-8/CXCL8 as compared to the control (p < 0.05). This
      pattern of increased mediator levels was observed regardless of the
      immunomodulatory drug regimen received (non-steroidal anti-inflammatory, steroids
      or immunosuppressants), and of the degree of tissue damage. Patients with
      anticardiolipin antibodies (ACAs) showed significantly higher levels of IL-8 and
      MIP-1beta than those with no ACAs. Levels of MCP-1/CCL2, MIP1-beta/CCL4 and IL
      8/CXCL8 correlated significantly, indicating a coordinated regulation of their
      secretion. Conversely, levels of Th1, Th2, Th17 cytokines, IFN-gamma and growth
      factors did not differ from those found in the healthy controls. IFN-alpha, IL
      1beta, IL-6, IL-7 and IL-13 were undetectable. In conclusion, long term treatment
      of SLE with standard immunomodulatory drug regimens fails to normalize levels of
      key chemoattractant proteins linked to innate immunity. This might suggest the
      existence of a basal, pro-inflammatory state in patients with lupus, even in the
      absence of symptoms, which could serve as a "substratum" or initiator of the
      immunological events taking place during a flare-up of the disease.

PMID- 20146994
TI  - Hemoglobin A1c in diabetes diagnosis: time for caution.

PMID- 20146995
TI  - Comments on the AACE/ACE statement on glycemic control for patients with type 2
      diabetes mellitus.

PMID- 20146996
TI  - Risk and health: disparities, gains, and the boot.

PMID- 20146997
TI  - Dampness and 2-ethyl-1-hexanol in floor construction of rehabilitation center:
      Health effects in staff.
AB  - The authors evaluated changes of symptoms and biomarkers in health care staff (N
      = 18) for people with different physical dysfunctions and similarly in an
      external office control group in a nondamp building (N = 15). The first workplace
      had verified dampness in the floor construction, with formation of 2-ethyl-1
      hexanol from water-based glue. Tear film break up time (BUT), nasal patency,
      biomarkers in nasal lavage (NAL), and dynamic spirometry were measured. Both
      buildings had low indoor air levels of CO2 (510 to 630 ppm), low levels of
      respirable particles (6 to 7 microg/m3) and formaldehyde (<5 microg/m3), and no
      indication of microbial growth. Pronounced increase of butanols and 2-ethyl-1
      hexanol levels were found in the damp floor material samples, but very low air
      levels of 2-ethyl-1-hexanol. The staff had been previously exposed to floor
      construction with alkaline degradation of floor glue, as well as formation of 2
      ethyl-1-hexanol. This led to an increase in their ocular, nasal, and respiratory
      symptoms, a decrease in nasal patency, and slight airway obstruction after 2 days
      of reexposure, possibly related to neutrophilic inflammation, after a 4-month
      exposure-free period.

PMID- 20146998
TI  - Respiratory and cardiovascular hospitalizations after the World Trade Center
      disaster.
AB  - The objective of this study was to determine whether there were increases in
      respiratory and cardiovascular hospital admissions among residents of lower
      Manhattan after the destruction of the World Trade Center. The authors used
      hospital admission records from 1991 to 2001 with a diagnosis of respiratory,
      cardiovascular, or cerebrovascular illness and a residential address in lower
      Manhattan or Queens. The authors assessed the change in admissions by comparing
      lower Manhattan to Queens (the control area) and before and after 9/11 admissions
      in lower Manhattan. They found the following significant increases in hospital
      admissions: for respiratory illnesses during the weeks of 9/11/01 and 10/16/01;
      asthma during the week of 9/11/01; cardiovascular during the weeks of 9/18/01 and
      10/9/01; cerebrovascular during the weeks of 9/11/01, 9/18/01, 10/2/01, and
      10/9/01. There was an immediate increase in respiratory admissions after the
      disaster and a delayed increase in cardiovascular and cerebrovascular admissions.

PMID- 20146999
TI  - Analysis of Nsukka metropolitan abattoir solid waste and its bacterial contents
      in south eastern Nigeria: public health implication.
AB  - This study was conducted to determine the quantum of waste generation and
      management and presence of major bacteria genera of public health importance in
      Nsukka municipal abattoir/slaughter house. The environment and public health
      implications of unhygienic sanitary condition at the abattoir and environs as a
      consequence of poor waste disposal and management were studied. A total of 194 kg
      of solid (rumen/stomach) wastes was generated daily without any clearly defined
      system of disposal and management. Forty-five rumen/stomach waste samples were
      examined for bacterial isolates using standard procedures. The isolation
      frequency showed that E. coli, Bacillus sp., and Staphylococcus sp. were more
      frequently isolated, followed by Streptococcus sp., Salmonella sp., and
      Campylobacter sp. Appropriate strategies for efficient solid waste disposal and
      management in our abattoirs were recommended.

PMID- 20147000
TI  - Erythrocyte cholinesterase enzyme activity and hemoglobin values in cacao farmers
      of southwestern Nigeria as related to insecticide exposure.
AB  - The blood of 76 cacao farmers from Southwestern Nigeria was monitored for
      erythrocyte cholinesterase enzyme activity (AChE) and hemoglobin values before
      and after insecticide application. Eight farmers had 30% to 50% baseline AChE
      activity, which suggests chronic organophosphate insecticide poisoning. AChE
      activity inhibition suggestive of occupational exposure (20% to 30%) was
      manifested by 28% of the farmers, whereas 30% to 50% inhibition suggestive of
      hazard was manifested by 11%. Significantly depressed post-insecticide
      application hemoglobin values were similarly recorded among the farmers. AChE
      activity inhibition, depression in hemoglobin values, and the years of
      involvement of the farmers in insecticide application on cacao, were positively
      correlated. Occupational exposure hazard due to organophosphate insecticides is
      therefore real among cacao farmers in Southwestern Nigeria. Regular biomonitoring
      of their blood for AChE activity and hemoglobin level is necessary.

PMID- 20147001
TI  - Environmental asbestos-related pleural plaque in southeast of Turkey.
AB  - It is known that many malignant and benign pleural diseases occur due to
      environmental exposure to mineral fibers. Calcified pleural plaque (CPP) is an
      important sign of asbestos exposure on chest radiographic examination. To study
      the possible change in the prevalence of CPP and diffuse pleural thickening 3
      decades after cessation of asbestos exposure. CPP were detected in 29.9% of the
      villagers; 4.7% had diffuse pleural thickening and 0.7% had asbestosis. The
      significant variable for CPP and diffuse pleural thickening was age. The youngest
      villager with CPP was 33 years of age and the prevalence of CPP increased with an
      increase in age. The reason for our cases with CPP being of advanced age is the
      discontinuation of asbestos exposure. This finding enables us to suggest that
      environmental asbestos-related disease will gradually decrease in future decades.

PMID- 20147002
TI  - Community-based participatory research in Boston's neighborhoods: A review of
      asthma case examples.
AB  - Three case examples of asthma studies that differ in terms of community and
      involvement are considered. The Boston Chinatown studies faced limited funding
      that restricted the level of community involvement, but resulted in some of the
      first published evidence about asthma in Asian American children. These studies
      led to an asthma education program grant to a local Asian clinic and elementary
      school. The public housing study was a well-funded multi-year study of asthma and
      pest management with city, university and community partners. Residents were
      trained to collect data and participated throughout the study. Follow up pest
      management and pesticide buy-back programs headed by the city and community
      partners have been funded. The Dorchester case had more limited funding, but had
      the greatest level of involvement of parents of asthmatic children in all phases
      of the research. This survey led to an interesting novel finding of lower asthma
      prevalence in foreign born black residents.

PMID- 20147003
TI  - The public minimization of the risks associated with environmental lead exposure
      and elevated blood lead levels in children, Mount Isa, Queensland, Australia.
AB  - This brief communication provides a critical evaluation of environmental lead
      problems, human health issues, and the minimisation of risks by industry and
      government authorities in Mount Isa, Queensland. Recent data indicates
      significantly elevated childhood blood lead levels in Mount Isa, and the evidence
      suggests health authorities have downplayed the risks of lead exposure in
      affected children. The minimisation of the risks of environmental lead exposure
      has led to complacency with respect to its harmful effects on human health. Given
      that the effects of lead exposure are largely irreversible, there is a strong
      argument for greater action at a government and industry level around community
      awareness, early intervention and regulatory controls.

PMID- 20147004
TI  - Effects of work place carbon monoxide exposure on blood viscosity.
AB  - Both blood viscosity and carbon monoxide (CO) has been associated with
      cardiovascular diseases (CVDs). In order to investigate the effects of chronic
      low-level CO exposure on the determinants of blood viscosity (hematocrit, plasma
      viscosity, erythrocyte deformability, and erythrocyte aggregation), 10 men
      exposed to CO at work for at least 6 months and 10 healthy controls were included
      in the study. Plasma viscosity was determined by a cone-plate viscometer,
      erythrocyte deformability and erythrocyte aggregation by laser-assisted optical
      rotational cell analyzer. Mean plasma viscosity of the group exposed to CO (1.4
      +/- 0.1 mPa.sn) was significantly higher than that of the controls (1.2 +/- 0.06
      mPa.sn) (p < .05). Plasma fibrinogen level of the CO group (275 +/- 11 mg/dL) was
      slightly higher than that of the controls (263 +/- 14 mg/dL). The rise in plasma
      viscosity by chronic low-level CO exposure may be the mechanism of CO-induced
      increase in the risk for CVDs.

PMID- 20147005
TI  - Health and urban ecosystems.

PMID- 20147006
TI  - Comparison of trial participants and open access users of a web-based physical
      activity intervention regarding adherence, attrition, and repeated participation.
AB  - BACKGROUND: Web-based interventions are popular for promoting healthy lifestyles
      such as physical activity. However, little is known about user characteristics,
      adherence, attrition, and predictors of repeated participation on open access
      physical activity websites. OBJECTIVE: The focus of this study was Active-online,
      a Web-based individually tailored physical activity intervention. The aims were
      (1) to assess and compare user characteristics and adherence to the website (a)
      in the open access context over time from 2003 to 2009, and (b) between trial
      participants and open access users; and (2) to analyze attrition and predictors
      of repeated use among participants in a randomized controlled trial compared with
      registered open access users. METHODS: Data routinely recorded in the Active
      online user database were used. Adherence was defined as: the number of pages
      viewed, the proportion of visits during which a tailored module was begun, the
      proportion of visits during which tailored feedback was received, and the time
      spent in the tailored modules. Adherence was analyzed according to six one-year
      periods (2003-2009) and according to the context (trial or open access) based on
      first visits and longest visits. Attrition and predictors of repeated
      participation were compared between trial participants and open access users.
      RESULTS: The number of recorded visits per year on Active-online decreased from
      42,626 in 2003-2004 to 8343 in 2008-2009 (each of six one-year time periods ran
      from April 23 to April 22 of the following year). The mean age of users was
      between 38.4 and 43.1 years in all time periods and both contexts. The proportion
      of women increased from 49.5% in 2003-2004 to 61.3% in 2008-2009 (P< .001). There
      were differences but no consistent time trends in adherence to Active-online. The
      mean age of trial participants was 43.1 years, and 74.9% were women. Comparing
      contexts, adherence was highest for registered open access users. For open access
      users, adherence was similar during the first and the longest visits; for trial
      participants, adherence was lower during the first visits and higher during the
      longest visits. Of registered open access users and trial participants, 25.8% and
      67.3% respectively visited Active-online repeatedly (P< .001). Predictors of
      repeated use were male sex (odds ratio [OR] = 1.2, 95% confidence interval [CI] =
      1.04-1.38) and increasing age category in registered open access users, and age
      46-60 versus < 30 years (OR = 3.04, 95% CI = 1.25-7.38) and Swiss nationality
      (OR(nonSwiss)= 0.64, 95% CI = 0.41-1.00) in trial participants. Despite reminder
      emails, attrition was much higher in registered open access users compared with
      trial participants, with a median lifetime website usage of 0 days in open access
      users and 290 days in trial participants. CONCLUSIONS: Adherence, patterns of
      use, attrition, and repeated participation differed between trial participants
      and open access users. Reminder emails to encourage repeated participation were
      effective for trial participants but not for registered open access users. These
      issues are important when interpreting results of randomized controlled
      effectiveness trials.

PMID- 20147007
TI  - Japanese quail: an efficient animal model for the production of transgenic
      avians.
AB  - The ability to generate transgenic mice has been a powerful tool in studying
      functional genomics, and much of our knowledge about developmental biology has
      come from the study of chicken embryology. Unfortunately, the availability of
      molecular genetic techniques, such as transgenics and knockouts, has been limited
      for developmental biologists using avian animal models. Efforts to develop a
      system for the rapid production of transgenic chickens have met with many
      obstacles, including high animal husbandry costs and long generational times.
      Recently, the Japanese quail has proven to be an excellent model organism for the
      production of transgenic avians using lentiviral vectors. The relatively small
      size of the adults, short time to sexual maturity, and prodigious egg production
      of the Japanese quail make development of transgenic lines less labor- and space
      intensive compared to chickens. The high degree of homology between chicken and
      quail genomes allows researchers to design highly specific DNA constructs for the
      production of transgenic birds. In addition, transgenic quail offer all of the
      advantages of the classic avian developmental model system, such as the ability
      to readily produce quail:chick transplant chimeras. Finally, Japanese quail are
      ideal for in ovo imaging of embryos expressing fluorescent reporters introduced
      from a transgene and/or electroporation. Here, we provide detailed methods for
      generating transgenic quail using high-titer lentivirus.

PMID- 20147008
TI  - The sea lamprey Petromyzon marinus: a model for evolutionary and developmental
      biology.
AB  - Sea lampreys (Petromyzon marinus) are cyclostomes, the most basal extant group of
      vertebrates, and are thought to have existed largely unchanged for more than 500
      million years. They are aquatic, eel-shaped animals that spend a major part of
      their life as filter-feeding larvae called ammocoetes, inhabiting many freshwater
      bodies in the northern hemisphere. After metamorphosis, sea lampreys migrate to
      the ocean (or to the Great Lakes), where they feed on the blood and bodily fluids
      of salmonid fish and ultimately return to freshwater streams and rivers to spawn
      and die. The unique evolutionary position of lampreys and the relative ease of
      obtaining mature adults and embryos make this animal an ideal model for
      investigations into early vertebrate evolution. Studies of features shared
      between lampreys and jawed vertebrates, but distinct from those in nonvertebrate
      chordates, have provided information on the origin and evolution of hallmark
      vertebrate characteristics such as the neural crest, ectodermal placodes, and
      jaw. In addition, studies of features that are unique to lampreys (e.g., the
      variable lymphocyte receptor-mediated immune system) provide insights into
      mechanisms of parallel evolution (e.g., the adaptive immune system). With the
      establishment of techniques for the extended maintenance and spawning of lampreys
      in the laboratory, the sequencing of the lamprey genome, and the adaptation and
      optimization of many established molecular biology and histochemistry techniques
      for use in this species, P. marinus is poised to become an evolutionary
      developmental model of choice.

PMID- 20147009
TI  - The crustacean Parhyale hawaiensis: a new model for arthropod development.
AB  - The great diversity of arthropod body plans, together with our detailed
      understanding of fruit fly development, makes arthropods a premier taxon for
      examining the evolutionary diversification of developmental patterns and hence
      the diversity of extant life. Crustaceans, in particular, show a remarkable range
      of morphologies and provide a useful outgroup to the insects. The amphipod
      crustacean Parhyale hawaiensis is becoming established as a model organism for
      developmental studies within the arthropods. In addition to its phylogenetically
      strategic position, P. hawaiensis has proven to be highly amenable to
      experimental manipulation, is straightforward to rear in the laboratory, and has
      large numbers of embryos that are available year-round. A detailed staging system
      has been developed to characterize P. hawaiensis embryogenesis. Robust protocols
      exist for the collection and fixation of all embryonic stages, in situ
      hybridization to study mRNA localization, and immunohistochemistry to study
      protein localization. Microinjection of blastomeres enables detailed cell-lineage
      analyses, transient and transgenic introduction of recombinant genetic material,
      and targeted knockdowns of gene function using either RNA interference (RNAi) or
      morpholino methods. Directed genome sequencing will generate important data for
      comparative studies aimed at understanding cis-regulatory evolution. Bacterial
      artificial chromosome (BAC) clones containing genes of interest to the
      developmental and evolutionary biology communities are being targeted for
      sequencing. An expressed sequence tag (EST) database will facilitate discovery of
      additional developmental genes and should broaden our understanding of the
      genetic controls of body patterning. A reference genome from the related amphipod
      crustacean Jassa slatteryi will shortly be available.

PMID- 20147010
TI  - Choosing the sequence of dsRNA for RNAi in mouse.
AB  - RNA interference (RNAi) is a suitable method for sequence-specific post
      transcriptional gene silencing for a number of model systems. Here, we describe
      selection of the target sequence for efficient RNAi knockdown in mouse.

PMID- 20147011
TI  - Cloning and sequencing an inverted repeat.
AB  - RNA interference (RNAi) is a suitable method for sequence-specific post
      transcriptional gene silencing for a number of model systems. The production of a
      transgene for transgenic RNAi in mouse can be accomplished by cloning an inverted
      repeat (IR) into the Zp3 transgenic cassette. Here, we describe three different
      strategies that have been used successfully to clone an IR: cloning by ligating
      polymerase chain reaction (PCR) products, sequential cloning using a short
      spacer, and sequential cloning using a temporary long spacer. Once cloning has
      been completed, sequencing the IR is the best way to assure that both arms are
      sufficiently long and intact; thus, we also describe typical problems one may
      encounter when sequencing IRs. There are two possible strategies for sequencing a
      cloned IR: (1) one internal primer at the end of the IR can be used to sequence
      both arms in a single sequencing run or (2) external primers can be used to
      sequence both arms separately. Although we have successfully sequenced IRs using
      both strategies, we suggest using the latter to sequence transgenic constructs.

PMID- 20147012
TI  - Generation of high-titer lentivirus for the production of transgenic quail.
AB  - This protocol describes how to generate high-titer lentivirus for the production
      of transgenic Japanese quail. The virus is pseudotyped with vesicular stomatitis
      virus with the envelope G glycoprotein (VSV-g), which gives a broad infectious
      range and allows concentration of viral supernatants by ultracentrifugation.
      Using this method, we typically produce titers >1 x 10(8) transforming units
      (TU)/mL and recommend using a virus with a titer at least this high for in vivo
      work.

PMID- 20147013
TI  - Injection of lentivirus into stage-X blastoderm for the production of transgenic
      quail.
AB  - This protocol describes how to generate transgenic quail by injecting a
      lentiviral vector into freshly laid Japanese quail eggs at stage X. The
      lentivirus infects primordial germ cells originating in the area pellucida.

PMID- 20147014
TI  - Screening for transgenic Japanese quail offspring.
AB  - After mosaic founder breeding pairs of Japanese quail start to produce fertile
      eggs, the hatchlings must be screened for germ-line transmission to the
      subsequent G1 generation. This article describes how to isolate hatchling genomic
      DNA from the chorioallantoic membrane (CAM), which remains inside the egg after
      hatching. Collecting genomic DNA from the CAM decreases the hatchling's stress
      during handling and eliminates the need for a blood draw. By following this
      protocol, the CAM of a single egg will provide 50 microg or more of high-quality
      genomic DNA. The article also describes how to screen the genomic DNA samples for
      the transgene by the polymerase chain reaction (PCR). PCR genotyping should be
      used for screening hatchlings with a nonfluorescent transgene or with a
      fluorescently labeled transgene that does not lend itself well to phenotypic
      screening.

PMID- 20147015
TI  - Assay for human Rad51-mediated DNA displacement loop formation.
AB  - Homologous recombination is an important mechanism for the repair of damaged
      chromosomes, for preventing the demise of damaged replication forks, and for
      several other aspects of chromosome metabolism and maintenance. The homologous
      recombination reaction is mediated by the Rad51 recombinase. In the presence of
      ATP, Rad51 polymerizes on single-stranded DNA (ssDNA) to form a nucleoprotein
      filament that is commonly referred to as the "presynaptic filament." The
      presynaptic filament is capable of locating a homologous duplex DNA molecule and
      catalyzing invasion of the duplex to form a DNA displacement loop called the "D
      loop." This protocol describes an in vitro D-loop assay that uses a radiolabeled
      ssDNA oligonucleotide and a nonlabeled homologous supercoiled duplex DNA as
      substrates, and agarose gel electrophoresis together with PhosphorImaging for
      product analysis. To enhance the efficiency of the D-loop reaction, an ancillary
      factor (the Hop2-Mnd1 complex or Rad54) is included in the reaction. This
      reconstituted system provides researchers a biochemical means to dissect the
      mechanisms of the homologous recombination machinery.

PMID- 20147017
TI  - Culturing lamprey embryos.
AB  - Lampreys are one of the most basal animals in which many of the true vertebrate
      characteristics (e.g., neural crest, placodes, segmented brain, skull, paired
      sensory organs, pharyngeal skeleton) are present. Studying the molecular and
      developmental mechanisms responsible for the formation of these structures in
      lamprey and higher vertebrates can provide insight into how these vertebrate
      characteristics evolved. The relative ease of obtaining mature adults and embryos
      makes this animal an ideal model for investigations into early vertebrate
      evolution. In addition, studies of features that are unique to lampreys can
      provide insights into mechanisms of parallel evolution. This protocol describes
      how to produce lamprey embryos by collecting sperm and eggs from mature lampreys,
      performing fertilization, and culturing the embryos through to the desired
      developmental stage.

PMID- 20147016
TI  - In vitro sumoylation of recombinant proteins and subsequent purification for use
      in enzymatic assays.
AB  - The sumoylation reaction is mechanistically similar to ubiquitination. It is ATP
      dependent and in vitro can be completed in two steps using purified E1
      (SAE1/SAE2), E2 (ubc9), and SUMO. Even without the inclusion of an E3 ligase,
      many substrates can be modified at the same lysines in vitro as in vivo. Here we
      describe a simplified in vitro sumoylation protocol using recombinant sumoylation
      substrate, E1, E2, SUMO, and an ATP-regenerating system. The modified substrate
      can then be repurified from the reaction mixture in a single step to be used in
      assays to assess the impact of sumoylation on enzymatic and/or other activities.

PMID- 20147018
TI  - Microinjection of RNA and morpholino oligos into lamprey embryos.
AB  - Lampreys are one of the most basal animals in which many of the true vertebrate
      characteristics (e.g., neural crest, placodes, segmented brain, skull, paired
      sensory organs, pharyngeal skeleton) are present. Studying the molecular and
      developmental mechanisms responsible for the formation of these structures in
      lamprey and higher vertebrates can provide insight into how these vertebrate
      characteristics evolved. The relative ease of obtaining mature adults and embryos
      makes this animal an ideal model for investigations into early vertebrate
      evolution. In addition, studies of features that are unique to lampreys can
      provide insights into mechanisms of parallel evolution. Lamprey embryos are
      particularly amenable to injection techniques. Like zebrafish and Xenopus
      embryos, they have double chorions and are resistant to surface-tension-induced
      rupture when removed from liquid. They can therefore be injected in a dry dish;
      this eliminates the need to support the embryo while performing injections and
      makes the procedure very rapid. Also, a single ovulating female can contain up to
      100,000 eggs, so the number of injectable embryos per fertilization is not a
      limiting factor. Finally, the second division lasts for several hours, providing
      a very large injection window. This protocol describes how to microinject RNA and
      morpholinos into lamprey embryos for genetic modification studies.

PMID- 20147019
TI  - DiI cell labeling in lamprey embryos.
AB  - Lampreys are one of the most basal animals in which many of the true vertebrate
      characteristics (e.g., neural crest, placodes, segmented brain, skull, paired
      sensory organs, pharyngeal skeleton) are present. Studying the molecular and
      developmental mechanisms responsible for the formation of these structures in
      lamprey and higher vertebrates can provide insight into how these vertebrate
      characteristics evolved. The relative ease of obtaining mature adults and embryos
      makes this animal an ideal model for investigations into early vertebrate
      evolution. In addition, studies of features that are unique to lampreys can
      provide insights into mechanisms of parallel evolution. Lamprey embryos are
      particularly amenable to injection techniques. Like zebrafish and Xenopus
      embryos, they have double chorions and are resistant to surface-tension-induced
      rupture when removed from liquid. They can therefore be injected in a dry dish;
      this eliminates the need to support the embryo while performing injections and
      makes the procedure very rapid. Also, a single ovulating female can contain up to
      100,000 eggs, so the number of injectable embryos per fertilization is not a
      limiting factor. This protocol describes how to label lamprey embryo cells by
      microinjecting the fluorescent dye DiI (1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate) to study cell fate during development.

PMID- 20147020
TI  - Whole-mount in situ hybridization on lamprey embryos.
AB  - Lampreys are one of the most basal animals in which many of the true vertebrate
      characteristics (e.g., neural crest, placodes, segmented brain, skull, paired
      sensory organs, pharyngeal skeleton) are present. Studying the molecular and
      developmental mechanisms responsible for the formation of these structures in
      lamprey and higher vertebrates can provide insight into how these vertebrate
      characteristics evolved. The relative ease of obtaining mature adults and embryos
      makes this animal an ideal model for investigations into early vertebrate
      evolution. In addition, studies of features that are unique to lampreys can
      provide insights into mechanisms of parallel evolution. This protocol describes
      an optimized procedure for RNA in situ hybridization in lamprey embryos.

PMID- 20147021
TI  - Immunostaining of whole-mount and sectioned lamprey embryos.
AB  - Lampreys are one of the most basal animals in which many of the true vertebrate
      characteristics (e.g., neural crest, placodes, segmented brain, skull, paired
      sensory organs, pharyngeal skeleton) are present. Studying the molecular and
      developmental mechanisms responsible for the formation of these structures in
      lamprey and higher vertebrates can provide insight into how these vertebrate
      characteristics evolved. The relative ease of obtaining mature adults and embryos
      makes this animal an ideal model for investigations into early vertebrate
      evolution. In addition, studies of features that are unique to lampreys can
      provide insights into mechanisms of parallel evolution. This protocol describes
      how to immunostain whole-mount or sectioned lamprey embryos using an antibody
      raised against the protein of interest and detected with a horseradish peroxidase
      (HRP)-conjugated secondary antibody.

PMID- 20147022
TI  - Fixation and dissection of Parhyale hawaiensis embryos.
AB  - The great diversity of arthropod body plans, together with our detailed
      understanding of fruit fly development, makes arthropods a premier taxon for
      examining the evolutionary diversification of developmental patterns and hence
      the diversity of extant life. Crustaceans, in particular, show a remarkable range
      of morphologies and provide a useful outgroup to the insects. The amphipod
      crustacean Parhyale hawaiensis is becoming established as a model organism for
      developmental studies within the arthropods. This protocol describes the
      dissection and fixation of P. hawaiensis embryos. Embryonic tissue fixed in the
      following manner is suitable for in situ hybridization experiments to study mRNA
      expression or for immunocytochemistry to study protein localization.

PMID- 20147023
TI  - Injection of Parhyale hawaiensis blastomeres with fluorescently labeled tracers.
AB  - The great diversity of arthropod body plans, together with our detailed
      understanding of fruit fly development, makes arthropods a premier taxon for
      examining the evolutionary diversification of developmental patterns and hence
      the diversity of extant life. Crustaceans, in particular, show a remarkable range
      of morphologies and provide a useful outgroup to the insects. The amphipod
      crustacean Parhyale hawaiensis is becoming established as a model organism for
      developmental studies within the arthropods. This protocol describes the
      injection of P. hawaiensis blastomeres with fluorescently labeled tracers for the
      purpose of cell-lineage analysis. The total (holoblastic) cleavages that
      characterize early embryogenesis in P. hawaiensis generate an eight-cell embryo
      with a stereotypical arrangement of blastomeres, each of which already possesses
      an invariant cell fate. Fluorochrome-conjugated dextran solutions, mRNAs encoding
      fluorescent proteins, and biotin-dextran have all proven to be useful lineage
      markers. The relative merits of various tracers are considered.

PMID- 20147024
TI  - Antibody staining of Parhyale hawaiensis embryos.
AB  - The great diversity of arthropod body plans, together with our detailed
      understanding of fruit fly development, makes arthropods a premier taxon for
      examining the evolutionary diversification of developmental patterns and hence
      the diversity of extant life. Crustaceans, in particular, show a remarkable range
      of morphologies and provide a useful outgroup to the insects. The amphipod
      crustacean Parhyale hawaiensis is becoming established as a model organism for
      developmental studies within the arthropods. This protocol provides a simplified
      protocol for antibody staining of P. hawaiensis embryos. The method also works
      well for other arthropods and phyla. Fixed embryos are rehydrated, washed,
      blocked with normal goat serum, and incubated overnight with primary antibody.
      Embryos are then washed and incubated with a peroxidase-conjugated secondary
      antibody that binds to the primary antibody. A subsequent histochemical reaction
      produces a black stain in those cells where antibodies have localized.

PMID- 20147025
TI  - In situ hybridization of labeled RNA probes to fixed Parhyale hawaiensis embryos.
AB  - The great diversity of arthropod body plans, together with our detailed
      understanding of fruit fly development, makes arthropods a premier taxon for
      examining the evolutionary diversification of developmental patterns and hence
      the diversity of extant life. Crustaceans, in particular, show a remarkable range
      of morphologies and provide a useful outgroup to the insects. The amphipod
      crustacean Parhyale hawaiensis is becoming established as a model organism for
      developmental studies within the arthropods. This protocol describes in situ
      hybridization of fluorescein- or digoxigenin (DIG)-labeled RNA probes to fixed P.
      hawaiensis embryos. Standard techniques of molecular biology should be used to
      produce an appropriate template for generation of antisense RNA probes. RNA
      labeling mixes designed to produce fluorescein- or DIG-labeled RNA probes using
      T3, T7, or SP6 RNA polymerases are commercially available. Probes should be
      purified using QIAGEN RNeasy columns or similar means. Considerations for double
      labeling experiments using both fluorescein- and DIG-labeled RNA probes are
      included.

PMID- 20147026
TI  - Preparation of dsRNA for microinjection experiments in mouse.
AB  - RNA interference (RNAi) is a suitable method for sequence-specific post
      transcriptional gene silencing for a number of model systems. The protocol
      presented here is designed for the preparation of microgram amounts of double
      stranded RNA (dsRNA) for microinjection experiments in mouse oocytes and early
      embryos. Briefly, dsRNA is produced after annealing sense and antisense RNA
      strands, or spontaneously during in vitro transcription of an inverted repeat. We
      usually include RNase T1 treatment of the annealed RNA prior to the purification
      step in order to remove unannealed single-stranded RNA (ssRNA), which can
      interfere with the quantification of dsRNA in a nondenaturing agarose gel.

PMID- 20147027
TI  - Microinjection of dsRNA into fully-grown mouse oocytes.
AB  - RNA interference (RNAi) is a suitable method for sequence-specific post
      transcriptional gene silencing in a number of model systems. The following
      protocol describes delivery of a double-stranded RNA (dsRNA) of choice into fully
      grown, germinal vesicle-intact (GV) mouse oocytes by microinjection.
      Microinjected oocytes can be cultured for up to 2 d or they can be matured to
      metaphase II. The metaphase II eggs can be fertilized in vitro and cultured up to
      the blastocyst stage. The efficiency of knockdown by RNAi can be assayed by
      quantitative reverse transcriptase (RT)-PCR (qPCR).

PMID- 20147028
TI  - Microinjection of dsRNA into mouse one-cell embryos.
AB  - RNA interference (RNAi) is a suitable method for sequence-specific post
      transcriptional gene silencing in a number of model systems. The following
      protocol describes delivery of a double-stranded RNA (dsRNA) of choice into mouse
      one-cell embryos by microinjection. Microinjected embryos can be cultured for up
      to 4 d, i.e., to the blastocyst stage. The efficiency of knockdown by RNAi can be
      assayed by quantitative reverse transcriptase (RT)-PCR (qPCR).

PMID- 20147029
TI  - Cloning a transgene for transgenic RNAi in mouse oocytes.
AB  - RNA interference (RNAi) is a suitable method for sequence-specific post
      transcriptional gene silencing for many model systems. The protocol presented
      here describes the cloning of a plasmid construct for use in transgenic RNAi
      experiments in mouse oocytes. The protocol is intended for production of a
      transgene by cloning an inverted repeat (IR) into the Zp3 transgenic cassette.
      The procedure begins with the selection of sequences and formulation of the
      cloning strategy. Subsequently, the IR is cloned, inserted into the transgenic
      cassette, and characterized by sequencing. Finally, the transgene is released
      from the cassette, purified, and provided to the transgenic facility.

PMID- 20147030
TI  - Microinjection of plasmids into meiotically incompetent mouse oocytes.
AB  - RNA interference (RNAi) is a suitable method for sequence-specific post
      transcriptional gene silencing in a number of model systems. The following
      protocol describes delivery of a mammalian double-stranded RNA (dsRNA) expression
      vector into meiotically incompetent mouse oocytes by microinjection. During mouse
      oocyte growth, there is a progressive decline in transcriptional activity, such
      that the fully-grown oocyte is transcriptionally quiescent. For this reason, the
      microinjection of plasmids should be performed in growing oocytes, obtained from
      12- to 13-d-old females. Microinjected oocytes can be cultured for up to 2 d. The
      efficiency of knockdown by RNAi can be assayed by quantitative reverse
      transcriptase (RT)-PCR (qPCR).

PMID- 20147032
TI  - RNAi experiments in mouse oocytes and early embryos.
AB  - The discovery of RNA interference (RNAi) in 1998 ushered in a new era in biology.
      RNAi currently serves as a favorite approach for inhibition of gene function in
      many areas of research. This article provides a brief review of RNAi and
      discussion of the benefits and drawbacks of using long double-stranded RNA
      (dsRNA) in mammalian oocytes and early embryos. We also provide an introduction
      to protocols for RNAi experiments in mouse, including preparation and
      microinjection of dsRNA into mouse oocytes and early embryos, and preparation and
      testing of constructs for transgenic RNAi based on long hairpin RNA expression.

PMID- 20147033
TI  - Maize (Zea mays): a model organism for basic and applied research in plant
      biology.
AB  - Zea mays ssp. mays is one of the world's most important crop plants, boasting a
      multibillion dollar annual revenue. In addition to its agronomic importance,
      maize has been a keystone model organism for basic research for nearly a century.
      Within the cereals, which include other plant model species such as rice (Oryza
      sativa), sorghum (Sorghum bicolor), wheat (Triticum spp.), and barley (Hordeum
      vulgare), maize is the most thoroughly researched genetic system. Several
      attributes of the maize plant, including a vast collection of mutant stocks,
      large heterochromatic chromosomes, extensive nucleotide diversity, and genic
      colinearity within related grasses, have positioned this species as a centerpiece
      for genetic, cytogenetic, and genomic research. As a model organism, maize is the
      subject of such far-ranging biological investigations as plant domestication,
      genome evolution, developmental physiology, epigenetics, pest resistance,
      heterosis, quantitative inheritance, and comparative genomics. These and other
      studies will be advanced by the completed sequencing and annotation of the maize
      gene space, which will be realized during 2009. Here we present an overview of
      the use of maize as a model system and provide links to several protocols that
      enable its genetic and genomic analysis.

PMID- 20147034
TI  - The 'mother of thousands' (Kalanchoe daigremontiana): a plant model for asexual
      reproduction and CAM studies.
AB  - The genus Kalanchoe plays an important role in the investigation of biochemical,
      physiological and phylogenetic aspects of Crassulacean acid metabolism (CAM) in
      plants, which is an important evolutionary adaptation of the photosynthetic
      carbon assimilation pathway to arid environments. In addition, natural compounds
      extracted from tissues of Kalanchoe have potential applicability in treating
      tumors and inflammatory and allergic diseases, and have been shown to have
      insecticidal properties. Kalanchoe daigremontiana (Hamet & Perrier) originated in
      Madagascar and reproduces asexually by spontaneously forming whole plantlets on
      leaves. Plantlets develop symmetrically along the leaf margins on leaf notches,
      closely resembling zygotic embryos in development, and once the root system is
      formed, they detach from the mother-leaf, fall to the ground, and grow into new
      plants. This phenomenon is also found in other species from this same genus;
      however, the formation of leaf-plantlets is variable among species. Nevertheless,
      all species illustrate the remarkable ability of plant somatic cells to
      regenerate an entire organism, which has fascinated the scientific community for
      many years. It was only recently that the morphogenic process involved in the
      origin of K. daigremontiana plantlets was determined using molecular and genetic
      tools: K. daigremontiana forms plantlets by co-opting both organogenesis and
      embryogenesis programs into leaves. The ability of K. daigremontiana species to
      form somatic embryos outside of a seed environment provides an attractive model
      system to study somatic embryogenesis in nature, particularly the molecular
      mechanism involved in the acquisition of competence by vegetative cells to make
      embryos without fertilization.

PMID- 20147036
TI  - Haploview: Visualization and analysis of SNP genotype data.
AB  - Association studies involve accessing, parsing, generating, and analyzing large
      volumes of data, often carried out in many steps over many months. Large-scale
      surveys of genetic variation, such as the International HapMap Project, and
      rapidly increasing volumes of single-nucleotide polymorphism (SNP) genotyping
      data have created exciting opportunities for association studies. However, they
      have further exacerbated the difficulty of curating and analyzing such data.
      Haploview is a program developed in Mark Daly's lab at the Broad Institute of MIT
      and Harvard, which is designed to bundle many everyday analysis tasks into one
      easy-to-use package. Haploview has several features that are useful throughout
      different phases of association studies. Several of these features are
      illustrated in this article by following a hypothetical association study from
      design to execution. Haploview is used to (1) analyze HapMap data and choose tag
      SNPs, (2) evaluate the quality of disease genotype data, (3) test for
      association, and (4) evaluate a region for follow-up of a positive association.

PMID- 20147035
TI  - The parasitoid wasp Nasonia: an emerging model system with haploid male genetics.
AB  - Nasonia is a complex of four closely related species of wasps that is rapidly
      emerging as a model for evolutionary and developmental genetics. It has several
      features that make it an excellent genetic system, including a short generation
      time, ease of rearing, interfertile species, visible and molecular markers, and a
      sequenced genome. The form of sex determination, called "haplodiploidy," makes
      Nasonia particularly suitable as a genetic tool. Females are diploid and develop
      from fertilized eggs, whereas males are haploid and develop from unfertilized
      eggs. This allows geneticists to exploit many of the advantages of haploid
      genetics in an otherwise complex eukaryotic organism. Nasonia readily inbreeds,
      permitting production of isogenic lines, and the four species in the genus are
      interfertile (after removal of the endosymbiont Wolbachia), facilitating movement
      of genes between the species for efficient positional cloning of quantitative
      trait loci (QTL). Genome sequencing of the genetic model Nasonia vitripennis and
      two interfertile species, Nasonia giraulti and Nasonia longicornis, is now
      completed. This genome project provides a wealth of interspecies polymorphisms
      (e.g., single nucleotide polymorphisms [SNPs], insertion-deletions [indels],
      microsatellites) to facilitate positional cloning of genes involved in species
      differences in behavior, morphology, and development. Advances in the genetics of
      this system also open a path for improvement of parasitoid insects as agents of
      pest control.

PMID- 20147037
TI  - High-resolution dual-trap optical tweezers with differential detection: managing
      environmental noise.
AB  - Optical traps or "optical tweezers" have become an indispensable tool in
      understanding fundamental biological processes. The ability to manipulate and
      probe individual molecules or molecular complexes has led to a new, more refined
      understanding of the mechanical properties of the fundamental building blocks of
      the cell, and of the mechanism by which molecular machines function. The
      minimization and management of noise are the keys to building a high-resolution
      optical tweezers. The high degree of stability needed to observe angstrom motions
      of a biological system places rather stringent requirements on the environment in
      which the instrument operates. Specifically, environmental noise is a concern
      when it leads to differential movements of the optical trap relative to the
      second attachment point of the tether. In this article, we discuss what entails a
      quiet environment--what sources of noise are relevant and how they affect the
      instrument--and provide guidelines for choosing an appropriate location for a
      high-resolution instrument.

PMID- 20147038
TI  - High-resolution dual-trap optical tweezers with differential detection:
      instrument design.
AB  - Optical traps or "optical tweezers" have become an indispensable tool in
      understanding fundamental biological processes. In this article, we present the
      design of a high-resolution optical tweezers, which is designed to minimize
      sensitivity to environmental noise. When the tether is attached to a stage,
      resolution is typically limited by drift and fluctuations in the relative
      position of the stage and trap-forming objective, cued by environmental noise. In
      a dual-trap design, however, the biological system is decoupled entirely from the
      stage by utilizing two optical traps to hold both ends of the tether. By holding
      each end of the molecule in an identical fashion, such dual-trap optical tweezers
      are less sensitive to drift and fluctuations of mechanical components. In our
      instrument, we form two traps from two orthogonally polarized beams generated by
      a single laser. As a result, many optical components and much of the optical path
      traveled are common to both trapping beams, thus minimizing differential
      movements of one optical trap relative to the other. Additionally, this
      economical use of optics creates an instrument that is simple and compact,
      reducing the number of elements susceptible to environmental fluctuations.

PMID- 20147039
TI  - High-resolution dual-trap optical tweezers with differential detection: data
      collection and instrument calibration.
AB  - Optical traps or "optical tweezers" have become an indispensable tool in
      understanding fundamental biological processes. Dual-trap optical tweezers with
      differential detection have the advantage that the instrument is decoupled from
      sources of environmental noise, thereby minimizing interference of signal and
      maximizing stability and spatial resolution. In this article, we describe methods
      of data detection and calibration for our dual-trap design.

PMID- 20147040
TI  - High-resolution dual-trap optical tweezers with differential detection:
      minimizing the influence of measurement noise.
AB  - Optical traps or "optical tweezers" have become an indispensable tool in
      understanding fundamental biological processes. The environment, the instrument
      components, and the overall design all have important roles in determining the
      spatial resolution of an optical trap. However, even with careful attention to
      these details, the spatial resolution of the optical tweezers is still
      fundamentally limited by the forces that induce Brownian fluctuations of the
      trapped microspheres. In this article, we focus on the ways in which the design
      and implementation of an experiment--the choice of bead size, tether length, and
      even the method in which the motions of the beads are monitored--can have a large
      impact on the fundamental resolution of the measurement. By investigating how the
      Brownian fluctuations depend on experimental parameters and the detection method,
      we develop a set of guidelines for designing a high-resolution experiment, with a
      prescription for minimizing the effect of Brownian fluctuations, thus maximizing
      the resolution of the experiment.

PMID- 20147041
TI  - High-resolution dual-trap optical tweezers with differential detection: alignment
      of instrument components.
AB  - Optical traps or "optical tweezers" have become an indispensable tool in
      understanding fundamental biological processes. Using our design, a dual-trap
      optical tweezers with differential detection, we can detect length changes to a
      DNA molecule tethering the trapped beads of 1 bp. By forming two traps from the
      same laser and maximizing the common optical paths of the two trapping beams, we
      decouple the instrument from many sources of environmental and instrumental noise
      that typically limit spatial resolution. The performance of a high-resolution
      instrument--the formation of strong traps, the minimization of background signals
      from trap movements, or the mitigation of the axial coupling, for example--can be
      greatly improved through careful alignment. This procedure, which is described in
      this article, starts from the laser and advances through the instrument,
      component by component. Alignment is complicated by the fact that the trapping
      light is in the near infrared (NIR) spectrum. Standard infrared viewing cards are
      commonly used to locate the beam, but unfortunately, bleach quickly. As an
      alternative, we use an IR-viewing charge-coupled device (CCD) camera equipped
      with a C-mount telephoto lens and display its image on a monitor. By visualizing
      the scattered light on a pair of irises of identical height separated by >12 in.,
      the beam direction can be set very accurately along a fixed axis.

PMID- 20147042
TI  - Phenotypic analysis of Arabidopsis mutants: oomycete pathogens.
AB  - Various fungal pathogens are used in Arabidopsis pathogen studies, including
      Fusarium oxysporum, Alternaria brassicicola, Botrytis cinerea, and others. The
      oomycete pathogen Peronospora parasitica has been used by several groups and is
      described in this protocol. Working with Peronospora is complicated by the fact
      that it is an obligate biotroph, and consequently cultures must be maintained on
      living plants. There is no central repository for Peronospora stocks, but most
      investigators who work with them are willing to provide samples of infected
      tissue. These can be used to initiate new stock cultures, or they can be
      maintained as live cultures on seedlings. One of the most important factors in
      maintaining Peronospora is the humidity of the growth chamber, which must be kept
      at a minimum of 80%. Various Peronospora isolates are available. These vary with
      respect to which Arabidopsis ecotypes they can infect, because some combinations
      trigger gene-for-gene resistance. Thus, it is important that the appropriate
      ecotype is inoculated with the appropriate strain of pathogen. The extent of
      infections can be rated or quantitatively measured as the number of spores
      produced per plant, and frozen tissue stocks can be prepared from heavily
      infected tissue.

PMID- 20147043
TI  - Fixation and paraffin-embedding of mouse tissues for GFP visualization.
AB  - Green fluorescent protein (GFP) and its variants are used in many applications,
      including protein localization, high-throughput screening, and gene discovery.
      Transgenes that use GFP-based proteins as a reporter provide a convenient way to
      follow protein expression over the course of development and disease progression
      in the mouse. The basic principle of visualizing fluorescent proteins is the same
      as for the fluorophores used in fluorescent microscopy. This protocol describes a
      method for fixation and paraffin-embedding of fresh mouse embryos or tissue for
      use in GFP microscopy.

PMID- 20147044
TI  - Analysis of in vivo protein complexes by coimmunoprecipitation from
      Caenorhabditis elegans.
AB  - Protein coimmunoprecipitation (co-IP) is a method used to analyze in vivo complex
      formation of various proteins. Although such an analysis supports the coexistence
      of proteins in a complex, a direct protein-protein interaction cannot be
      concluded unless further in vitro data are available. This protocol describes how
      to perform co-IPs from C. elegans whole-worm extracts using protein-specific
      antibodies. First, we describe how to culture a large number of worms while
      maintaining their overall appearance and wild-type fertility rates, which are
      important factors when analyzing the germline tissue. Next, we present a gentle
      and effective method to generate worm extracts with high protein concentrations
      that maintain protein complexes of high quality. Finally, we describe how to
      purify the protein of choice along with its associated complex members. The
      precipitated protein complex can be analyzed by either immunoblot analysis or
      mass spectrometry to identify the copurified protein components. When working
      with RNA-binding proteins, it is of interest to assess whether RNA molecules,
      rather than a direct interaction between the proteins, might mediate complex
      formation. For this purpose, an optional RNase digestion step to degrade the RNA
      in the extract is described.

PMID- 20147045
TI  - Analysis of RNA-protein complexes by RNA coimmunoprecipitation and RT-PCR
      analysis from Caenorhabditis elegans.
AB  - RNA coimmunoprecipitation (co-IP) experiments are an extension of protein co-IP
      experiments in which in vivo RNA-protein complexes are investigated. This
      protocol describes how to perform RNA co-IPs from C. elegans whole-worm extracts.
      In principle, a protein-specific antibody is used to purify the protein of choice
      and its associated complex members from worm extract. This may also include RNA
      molecules associated with other protein components. To identify a specific mRNA
      molecule, all RNA molecules are first separated from the protein components after
      immunopurification. The mRNAs are then converted into cDNA by reverse
      transcription. Candidate mRNAs are detected by sensitive gene-specific
      amplification via polymerase chain reaction (PCR) in a semiquantitative manner.
      Since RNA molecules are very prone to degradation, it is crucial to avoid any
      kind of contamination with RNase activity in this experiment.

PMID- 20147046
TI  - Fixing and sectioning tissue from the plant Kalanchoe daigremontiana.
AB  - Tissue samples from Kalanchoe daigremontiana can be fixed for scanning electron
      microscopy (SEM), histology, and in situ hybridization using several common steps
      described in this protocol. All steps should be performed in the same manner for
      all three methods unless otherwise noted.

PMID- 20147047
TI  - In situ hybridization in the plant Kalanchoe daigremontiana.
AB  - Here we describe in detail the detection of gene expression in plant tissues of
      Kalanchoe daigremontiana by in situ hybridization analyses. Included are methods
      for making RNA transcript probes, probe-tissue hybridization, and detection of
      antisense RNA probes. The in situ hybridization technique is used to determine
      which cells or group of cells in particular tissue(s) express a gene of interest.

PMID- 20147048
TI  - Transformation of the plant Kalanchoe daigremontiana using Agrobacterium
      tumefaciens.
AB  - Kalanchoe daigremontiana can be stably transformed using the Agrobacterium
      tumefaciens-mediated T-DNA transfer method, as described here. Sterilized plant
      tissue is cocultivated with an A. tumefaciens suspension, transformants are
      selected and the shoots are grown in rooting medium and then in soil. Plant
      phenotypes can be examined approximately 3 mo after transfer of plants to soil.

PMID- 20147049
TI  - Extraction of DNA from the plant Kalanchoe daigremontiana.
AB  - This protocol describes how to isolate genomic DNA from leaves and stems of
      Kalanchoe daigremontiana. The procedure can be applied to adult leaves, but it is
      best to use younger leaves because they have fewer secondary metabolites and
      polysaccharides, which can interfere with the DNA extraction. The resulting DNA
      can be used for polymerase chain reactions (PCRs), Southern blots, or other
      applications.

PMID- 20147050
TI  - Extraction of RNA from the plant Kalanchoe daigremontiana.
AB  - This protocol describes how to isolate total RNA from several tissues of
      Kalanchoe daigremontiana. Total RNA can be isolated by using the TRI-reagent
      method, scaled up for processing 2 g of tissue, or by using the protocol
      described here, which gives higher concentrations of high quality RNA. The
      resulting RNA can be used for various applications including generation of cDNA
      for reverse transcriptase-PCR (RT-PCR), Northern blots, or other purposes.

PMID- 20147051
TI  - Formation and use of water-soluble lipopolymer-pDNA and lipopeptide-pDNA
      complexes.
AB  - Water-soluble lipopolymers and lipopeptides are nonviral gene-transfer reagents
      that combine the advantages of lipids, which increase permeability of DNA through
      cell membranes, with the DNA-condensing and enhanced endosomal release properties
      of polycations. This protocol describes the synthesis and characterization of
      water-soluble lipopolymer/lipopeptide-DNA complexes and their use in transfection
      of cultured cells and injection into tumor-bearing mice. Lipopolymers are formed
      by conjugating cholesteryl chloroformate with the primary or secondary amines of
      1800-Da branched polyethylenimine (PEI); the use of the 1800-Da PEI avoids the
      cytotoxicity problems associated with higher molecular-mass PEI. Lipopeptides are
      composed of a human protamine-derived peptide that has been incubated with a
      reaction of O-(N-succinimidyl)-N,N,N',N',-tetramethyluronium tetrafluoroborate
      with lithocholic acid in the presence of excess diisopropylethylamine. The
      therapeutic gene used as an example in this protocol encodes the murine
      interleukin 12 (IL-12) subunits p35 and p40, each under the transcriptional
      control of a separate cytomegalovirus (CMV) promoter; the reporter plasmid
      contains the luciferase gene driven by a CMV promoter. The target cells are C-26
      colon carcinoma cells.

PMID- 20147052
TI  - Strain maintenance of Nasonia vitripennis (parasitoid wasp).
AB  - Nasonia is a complex of four closely related species of wasps with several
      features that make it an excellent system for a variety of genetic studies. These
      include a short generation time, ease of rearing, interfertile species, visible
      and molecular markers, and a sequenced genome. Furthermore, its parasitoid
      lifestyle allows investigations of questions relating to parasitoid/host
      dynamics, host preference, and specialist versus generalist biology. It also can
      serve as a behavior model for studies of courtship, male aggression and
      territoriality, female dispersal, and sex ratio control. This protocol describes
      standard rearing of Nasonia vitripennis strains on Sarcophaga bullata hosts.

PMID- 20147053
TI  - Rearing Sarcophaga bullata fly hosts for Nasonia (parasitoid wasp).
AB  - Nasonia is a complex of four closely related species of wasps with several
      features that make it an excellent system for a variety of genetic studies. These
      include a short generation time, ease of rearing, interfertile species, visible
      and molecular markers, and a sequenced genome. It also can serve as a behavior
      model for studies of courtship, male aggression and territoriality, female
      dispersal, and sex ratio control. Nasonia vitripennis is a parasitoid of a number
      of calliphorid flies, such as Sarcophaga bullata, allowing investigations of
      questions relating to parasitoid/host dynamics, host preference, and specialist
      versus generalist biology. S. bullata are relatively large, increasing the
      offspring yield that a single N. vitripennis female can produce. They are also
      easily reared in the lab if proper ventilation is available. This protocol
      describes the methods to collect and raise S. bullata larvae that will be used as
      hosts for N. vitripennis.

PMID- 20147054
TI  - Egg collection for Nasonia (parasitoid wasp).
AB  - Nasonia is a complex of four closely related species of wasps with several
      features that make it an excellent system for a variety of genetic studies. These
      include a short generation time, ease of rearing, interfertile species, visible
      and molecular markers, and a sequenced genome. Furthermore, its parasitoid
      lifestyle allows investigations of questions relating to parasitoid/host
      dynamics, host preference, and specialist versus generalist biology. It also can
      serve as a behavior model for studies of courtship, male aggression and
      territoriality, female dispersal, and sex ratio control. This protocol describes
      methods to count and/or collect Nasonia eggs. Fly hosts are placed in a foam plug
      such that only one oviposition site is available to the female wasp.

PMID- 20147055
TI  - Virgin collection and haplodiploid crossing methods in Nasonia (parasitoid wasp).
AB  - This protocol covers most procedures used by the Nasonia (wasp) geneticist,
      including virgin collection. Nasonia are easily sexed as pupae, so collecting
      virgins can easily be performed within a window of several days. The female
      specific ovipositor is visible at even the earliest pupal stages as a
      longitudinal ridge on the ventral posterior abdomen. To prolong generations,
      yellow pupae can be stored at 4 degrees C-8 degrees C for up to 2 mo and adults
      for 2-3 wk. In the example presented here, haplodiploid crossing methods are used
      to make a new Nasonia vitripennis mutant homozygous, using an aunt/nephew mating
      approach. The protocol can be extended to inbreeding strains. Inbreeding
      depression generally is not a problem in Nasonia unless the mutation itself is
      female-sterile. Mother/son mating and sib mating are also reasonable approaches
      to inbreeding.

PMID- 20147056
TI  - Larval RNAi in Nasonia (parasitoid wasp).
AB  - Nasonia is a complex of four closely related species of wasps with several
      features that make it an excellent system for a variety of genetic studies. These
      include a short generation time, ease of rearing, interfertile species, visible
      and molecular markers, and a sequenced genome. Furthermore, its parasitoid
      lifestyle allows investigations of questions relating to parasitoid/host
      dynamics, host preference, and specialist versus generalist biology. It also can
      serve as a behavior model for studies of courtship, male aggression and
      territoriality, female dispersal, and sex ratio control. This protocol describes
      a method to use RNA interference (RNAi) to knock down genes in Nasonia larvae.
      Unlike in Drosophila, RNAi in Nasonia is systemic. In the example presented here,
      adult red-eye-color phenotypes are produced by injecting double-stranded RNA
      (dsRNA) against the eye color gene cinnabar into last-instar Nasonia larvae.

PMID- 20147057
TI  - Curing Wolbachia infections in Nasonia (parasitoid wasp).
AB  - Nasonia is a complex of four closely related species of wasps with several
      features that make it an excellent system for a variety of genetic studies. These
      include a short generation time, ease of rearing, interfertile species, visible
      and molecular markers, and a sequenced genome. However, the Nasonia species
      normally are completely or partially reproductively isolated owing to Wolbachia,
      widespread intracellular bacteria found in arthropods and nematodes. Wolbachia
      cause cytoplasmic incompatibility (CI) in Nasonia. Although the current genome
      sequenced strains of Nasonia (AsymCX, IV7[u], RV2X[u]) are all Wolbachia-free,
      crosses between infected and uninfected wasps, or between infected wasps of
      different species, will fail because of Wolbachia. The sperm modification that
      induces CI appears to be established before the adult stage, so it is generally
      not possible to cure an infection and break the CI barrier in the same
      generation. However, a Wolbachia infection can be removed from a strain over a
      number of generations by feeding antibiotics and selecting on females showing
      partial CI. This protocol describes the methods to cure a Nasonia strain of its
      Wolbachia symbionts.

PMID- 20147058
TI  - Field collection of Nasonia (parasitoid wasp) using baits.
AB  - This protocol describes a standard method for collecting Nasonia wasps using
      "flyliver": liver remains fed upon by fly maggots (e.g., Sarcophaga) and
      collected after the mature larvae have dispersed. The flyliver, which contains a
      volatile substance that is very attractive to the wasps, is placed in a large
      (approximately 15-cm(2)) mesh bag hung in appropriate collection spots (e.g.,
      near birds' nests or under culverts). Within the large mesh bag is a smaller mesh
      bag placed abutting the flyliver and containing four to six Sarcophaga pupae.
      These retain the wasps, which will enter the bag and begin stinging the hosts.
      The mesh bags can be made with standard nylon window screening, or any other
      material with mesh width large enough to permit entry of the wasps.

PMID- 20147059
TI  - Quantitative real-time RT-PCR (qRT-PCR) of zebrafish transcripts: optimization of
      RNA extraction, quality control considerations, and data analysis.
AB  - The zebrafish (Danio rerio) has emerged as a popular model species. The rapid
      development of zebrafish embryos provides opportunities for investigation of
      genes essential for developmental processes, the human counterparts of which
      might be implicated in diseases. Understanding when and where genes are expressed
      can facilitate greater understanding of their function, and also allow the genes
      to be manipulated by gene knockdown in temporally and spatially specific manners.
      Quantitative real-time polymerase chain reaction (qRT-PCR) is widely applied in
      gene expression studies. This protocol presents techniques to optimize RNA
      isolation from zebrafish embryos; quality assessment and the use of multiple
      reference genes are also emphasized. The combined use of TRIzol extraction and
      column-based purification is strongly recommended, because the resulting RNA is
      of better quality than RNA isolated using either of those methods alone. The
      procedure can be performed in 2 d, with individual stages taking up to 15 h to
      complete.

PMID- 20147062
TI  - High-resolution dual-trap optical tweezers with differential detection: an
      introduction.
AB  - Optical traps or "optical tweezers" have become an indispensable tool in
      understanding fundamental biological processes. The ability to manipulate and
      probe individual molecules or molecular complexes has led to a new, more refined
      understanding of the mechanical properties of the fundamental building blocks of
      the cell, and of the mechanism by which molecular machines function. The field
      has seen a steady stream of technological advances that have greatly refined the
      technique. One major effort has been in developing methods to resolve motions at
      the angstrom level--the fundamental length scale for many biological processes.
      This drive has only recently come to fruition with the advent of high-resolution
      optical trapping techniques that can now detect movements on the scale of a
      single base pair of DNA, 3.4 A. Here we briefly review the basic concepts and
      components of optical traps and the single-molecule experiments in which they are
      used.

PMID- 20147063
TI  - The moss Physcomitrella patens: a novel model system for plant development and
      genomic studies.

PMID- 20147064
TI  - The choanoflagellates: heterotrophic nanoflagellates and sister group of the
      metazoa.

PMID- 20147065
TI  - In-gel trypsin digest of gel-fractionated proteins.

PMID- 20147066
TI  - Culturing the moss Physcomitrella patens.

PMID- 20147067
TI  - Chromosome conformation capture.

PMID- 20147068
TI  - DNA extraction from formalin-fixed, paraffin-embedded tissue.

PMID- 20147069
TI  - Virus-induced gene silencing as a tool for delivery of dsRNA into plants.

PMID- 20147070
TI  - Isolation and regeneration of protoplasts of the moss Physcomitrella patens.

PMID- 20147071
TI  - Somatic hybridization in the moss Physcomitrella patens using PEG-induced
      protoplast fusion.

PMID- 20147072
TI  - Chemical and UV mutagenesis of spores and protonemal tissue from the moss
      Physcomitrella patens.

PMID- 20147073
TI  - Transformation of the moss Physcomitrella patens using direct DNA uptake by
      protoplasts.

PMID- 20147074
TI  - Transformation of the moss Physcomitrella patens using T-DNA mutagenesis.

PMID- 20147075
TI  - Transformation of moss Physcomitrella patens gametophytes using a biolistic
      projectile delivery system.

PMID- 20147076
TI  - Isolation of DNA, RNA, and protein from the moss Physcomitrella patens
      gametophytes.

PMID- 20147077
TI  - Isolation of single choanoflagellate cells from field samples and establishment
      of clonal cultures.

PMID- 20147078
TI  - Starting and maintaining Monosiga brevicollis cultures.

PMID- 20147079
TI  - Long-term frozen storage of choanoflagellate cultures.

PMID- 20147080
TI  - Visualizing the subcellular localization of actin, beta-tubulin, and DNA in
      Monosiga brevicollis.

PMID- 20147081
TI  - Preparation of total RNA from Monosiga brevicollis and other choanoflagellates.

PMID- 20147082
TI  - Rapid preparation of genomic DNA from Monosiga brevicollis and other
      choanoflagellates.

PMID- 20147083
TI  - Preparation of high-molecular-weight genomic DNA from Monosiga brevicollis and
      other choanoflagellates.

PMID- 20147084
TI  - Separation of choanoflagellate and bacterial genomic DNA.

PMID- 20147085
TI  - A simple free-radical polymerization method for the fabrication of microscale
      acrylonitrile fibers for cellular probing.

PMID- 20147086
TI  - The OP9-DL1 system: generation of T-lymphocytes from embryonic or hematopoietic
      stem cells in vitro.

PMID- 20147090
TI  - Basics of photoactivation.

PMID- 20147091
TI  - The short-tailed fruit bat Carollia perspicillata: a model for studies in
      reproduction and development.

PMID- 20147092
TI  - Darwin's finches: analysis of beak morphological changes during evolution.

PMID- 20147093
TI  - PCR primer design.

PMID- 20147094
TI  - Feeding short-tailed fruit bats (Carollia perspicillata).

PMID- 20147095
TI  - Generating timed pregnancies in fruit bats (Carollia perspicillata).

PMID- 20147096
TI  - Collection of short-tailed fruit bats (Carollia perspicillata) from the wild.

PMID- 20147097
TI  - Collection of embryos from short-tailed fruit bats (Carollia perspicillata).

PMID- 20147098
TI  - Fixation and storage of embryos from short-tailed fruit bat (Carollia
      perspicillata).

PMID- 20147099
TI  - Whole-mount in situ hybridization of short-tailed fruit bat (Carollia
      perspicillata) embryos with RNA probes.

PMID- 20147100
TI  - Alcian blue staining of cartilage of short-tailed fruit bat (Carollia
      perspicillata).

PMID- 20147101
TI  - Alcian blue/alizarin red staining of cartilage and bone of short-tailed fruit bat
      (Carollia perspicillata).

PMID- 20147102
TI  - Whole-mount immunohistochemistry of short-tailed fruit bat (Carollia
      perspicillata).

PMID- 20147103
TI  - Combined 3C-ChIP-cloning (6C) assay: a tool to unravel protein-mediated genome
      architecture.

PMID- 20147104
TI  - Alcian blue staining of the mouse fetal cartilaginous skeleton.

PMID- 20147105
TI  - Alcian blue/alizarin red staining of cartilage and bone in mouse.

PMID- 20147106
TI  - Alizarin red staining of post-natal bone in mouse.

PMID- 20147107
TI  - Regulating protein stability in mammalian cells using small molecules.

PMID- 20147108
TI  - A general method for conditional regulation of protein stability in living
      animals.

PMID- 20147109
TI  - Collection of embryos from Darwin's finches (Thraupidae, Passeriformes).

PMID- 20147110
TI  - In situ hybridization analysis of embryonic beak tissue from Darwin's finches.

PMID- 20147111
TI  - Microarray analysis of embryonic beak mRNA from Darwin's finches.

PMID- 20147112
TI  - Cetyltrimethyl ammonium bromide (CTAB) DNA miniprep for plant DNA isolation.

PMID- 20147113
TI  - Dellaporta miniprep for plant DNA isolation.

PMID- 20147114
TI  - Quick miniprep for plant DNA isolation.

PMID- 20147115
TI  - Mass spectrometry characterization of multiprotein complexes.

PMID- 20147116
TI  - Preparation of recombinant baculoviruses with the BVboost system.

PMID- 20147117
TI  - Transduction of vertebrate cells with recombinant baculovirus.

PMID- 20147120
TI  - The snail Ilyanassa: a reemerging model for studies in development.
AB  - Ilyanassa obsoleta is a marine gastropod that is a long-standing and very useful
      model for studies of embryonic development. It is especially important as a model
      for the spiralian development program, a distinctive mode of early development
      shared by a large group of animal phyla, but poorly understood. Ilyanassa adults
      are readily obtainable and easy to keep in the laboratory, and they produce large
      numbers of embryos throughout most of the year. The embryos are amenable to
      classic embryological manipulation techniques as well as a growing number of
      molecular approaches. In this article, we present an overview of aspects of its
      biology and use as a model organism.

PMID- 20147121
TI  - Helobdella (leech): a model for developmental studies.
AB  - Helobdella is a genus of freshwater leeches, several species of which have been
      used for developmental studies since the 1970s. Helobdella embryos have been used
      for cell-lineage tracing and dye-mediated photoablation, and they have also been
      very useful for studies in cellular neurobiology. In this article, we discuss the
      reasons that Helobdella is used for studying development and some of the
      questions that are addressed through the use of this organism.

PMID- 20147122
TI  - Optimization and troubleshooting in PCR.
AB  - The use of polymerase chain reaction (PCR) to generate large amounts of a desired
      product can be a double-edged sword. Failure to amplify under optimum conditions
      can lead to the generation of multiple undefined and unwanted products, even to
      the exclusion of the desired product. At the other extreme, no product may be
      produced. A typical response at this point is to vary one or more of the many
      parameters that are known to contribute to primer-template fidelity and primer
      extension. High on the list of optimization variables are Mg(++) concentrations,
      buffer pH, and cycling conditions. With regard to the last, the annealing
      temperature is most important. The situation is further complicated by the fact
      that some of the variables are quite interdependent. For example, because dNTPs
      directly chelate a proportional number of Mg(++) ions, an increase in the
      concentration of dNTPs decreases the concentration of free Mg(++) available to
      influence polymerase function. This article discusses various optimization
      strategies, including touchdown PCR and hot-start PCR.

PMID- 20147123
TI  - Reconstitution of nucleosomal arrays using recombinant Drosophila ACF and NAP1.
AB  - The goal of chromatin assembly procedures is to prepare extended nucleosomal
      arrays from cloned DNA templates and purified core and linker histones. The
      assembled chromatin should be highly defined in its protein content and resemble
      bulk chromatin isolated from living cell nuclei in terms of periodicity and
      nucleosome positioning. This protocol describes how to assemble minichromosome
      templates in an ATP-dependent fashion from circular plasmid DNA and purified core
      histones. This system can also be used to assemble minichromosomes from linear
      DNA (plasmid and lambda) and can also incorporate proteins other than core
      histones (linker histone H1, HMG17, and DNA-binding transcription factors). The
      products of the chromatin assembly reaction can be used directly (or after
      purification) in assays to study transcription, DNA replication, recombination,
      and repair. The system uses purified recombinant Drosophila chromatin assembly
      factors ACF (ATP-utilizing chromatin assembly and remodeling factor) and NAP1
      (nucleosome assembly protein 1).

PMID- 20147124
TI  - Purification of recombinant Drosophila ACF.
AB  - The goal of chromatin assembly procedures is to prepare extended nucleosomal
      arrays from cloned DNA templates and purified core and linker histones. The
      assembled chromatin should be highly defined in its protein content and resemble
      bulk chromatin isolated from living cell nuclei in terms of periodicity and
      nucleosome positioning. This protocol describes the preparation of Drosophila ACF
      (ATP-utilizing chromatin assembly and remodeling factor) for use in chromatin
      assembly reactions. In this method, ACF is prepared by the coexpression of the
      carboxyl-terminally FLAG-tagged Acf1 subunit with the untagged ISWI subunit in
      baculovirus. The complex is then purified in one step by FLAG immunoaffinity
      chromatography. This procedure typically results in a stoichiometric complex of
      Acf1 and ISWI.

PMID- 20147125
TI  - Purification of recombinant Drosophila NAP1.
AB  - The goal of chromatin assembly procedures is to prepare extended nucleosomal
      arrays from cloned DNA templates and purified core and linker histones. The
      assembled chromatin should be highly defined in its protein content and resemble
      bulk chromatin isolated from living cell nuclei in terms of periodicity and
      nucleosome positioning. This protocol describes the preparation of the NAP1
      chaperone protein for use in chromatin assembly reactions. In this method, Sf9
      cells are infected with an HIS6-DNA-1-expressing baculovirus. The NAP1 is then
      purified by nickel affinity chromatography, followed by anion-exchange
      chromatography.

PMID- 20147126
TI  - Obtaining Ilyanassa snail embryos.
AB  - The marine gastropod Ilyanassa obsoleta is a long-standing and very useful model
      for studies of embryonic development. It is an especially important model for
      spiralian development, and for studies of asymmetric cell division. The embryos
      are amenable to classic embryological manipulation techniques as well as a
      growing number of molecular approaches. Ilyanassa is also an important model for
      studies of metamorphosis, the ecology of parasitism, the effects of environmental
      contaminants on morphology and sexual function, and comparative neurobiology.
      Ilyanassa adults are readily obtainable and easy to keep in the laboratory.
      Although the normal spawning season for Ilyanassa is during early summer, they
      can produce high-quality embryos nearly year-round in the laboratory. Snails
      collected in the late fall, winter, or spring can be induced to deposit zygotes
      before the natural spawning season by warming them to room temperature, and
      snails collected before the natural spawning season can be made to postpone
      zygote deposition until needed (up to at least 6 mo) by maintaining them in tanks
      in a cold room at 4 degrees C-8 degrees C. This protocol describes how to induce
      embryo production in Ilyanassa snails, collect the embryos, and rear them to the
      stage required for study.

PMID- 20147127
TI  - Induction of larval metamorphosis in the snail Ilyanassa.
AB  - The marine gastropod Ilyanassa obsoleta is a long-standing and very useful model
      for studies of embryonic development. It is an especially important model for
      spiralian development, and for studies of asymmetric cell division. The embryos
      are amenable to classic embryological manipulation techniques as well as a
      growing number of molecular approaches. Ilyanassa is also an important model for
      studies of metamorphosis, the ecology of parasitism, the effects of environmental
      contaminants on morphology and sexual function, and comparative neurobiology.
      Ilyanassa adults are readily obtainable and easy to keep in the laboratory, and
      they can produce high-quality embryos nearly year-round in the laboratory. After
      hatching from capsules, larval Ilyanassa can be maintained in culture, feeding on
      single-celled algae. The larvae will become competent to undergo metamorphosis
      after approximately 3 wk in culture. Metamorphosis can be induced artificially by
      treating with either the neurotransmitter serotonin or the nitric oxide synthase
      inhibitor 7-nitroindazole. Both of these reagents have been shown to induce
      metamorphosis in >75% of larvae within 48 h. This protocol describes the
      induction of metamorphosis in snail larvae.

PMID- 20147128
TI  - Pressure injection of Ilyanassa snail embryos.
AB  - The marine gastropod Ilyanassa obsoleta is a long-standing and very useful model
      for studies of embryonic development. It is an especially important model for
      spiralian development, and for studies of asymmetric cell division. The embryos
      are amenable to classic embryological manipulation techniques, as well as a
      growing number of molecular approaches. Ilyanassa is also an important model for
      studies of metamorphosis, the ecology of parasitism, the effects of environmental
      contaminants on morphology and sexual function, and comparative neurobiology.
      Intracellular microinjection is an important tool, especially for lineage tracing
      and perturbations of specific genes by knockdown approaches and synthetic mRNA
      injections. Two methods for the introduction of lineage tracers into particular
      cells are routine in Ilyanassa. Iontophoresis of charged molecules, such as
      fluorophore-dextran conjugates can be accomplished using a simply built current
      generator. Injection of an oil-based solution containing the fluorescent probe
      1,1-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI) is also
      straightforward. However, injection of oil-based solutions and iontophoresis have
      not been useful for delivering water-soluble reagents to perturb gene function,
      and pressure injection of aqueous solutions has been more challenging. This
      protocol describes a recently optimized procedure for the pressure injection of
      aqueous solutions into Ilyanassa embryos and zygotes with high rates of survival
      and normal development. The key parameters seem to be the injection needles,
      injection media, and the stage of injected embryos.

PMID- 20147129
TI  - Fixation of Ilyanassa snail embryos and larvae.
AB  - The marine gastropod Ilyanassa obsoleta is a long-standing and very useful model
      for studies of embryonic development. It is an especially important model for
      spiralian development, and for studies of asymmetric cell division. The embryos
      are amenable to classic embryological manipulation techniques, as well as a
      growing number of molecular approaches. Ilyanassa is also an important model for
      studies of metamorphosis, the ecology of parasitism, the effects of environmental
      contaminants on morphology and sexual function, and comparative neurobiology.
      Ilyanassa embryos are particularly well suited for RNA and protein localization
      studies because of the relatively large cells and favorable properties for
      imaging. This protocol describes how to fix and store Ilyanassa embryos and
      larvae for use in whole-mount in situ hybridization and immunohistochemical
      studies.

PMID- 20147130
TI  - Isolation of genomic DNA from Ilyanassa snail larvae.
AB  - The marine gastropod Ilyanassa obsoleta is a long-standing and very useful model
      for studies of embryonic development. It is an especially important model for
      spiralian development, and for studies of asymmetric cell division. The embryos
      are amenable to classic embryological manipulation techniques as well as a
      growing number of molecular approaches. Ilyanassa is also an important model for
      studies of metamorphosis, the ecology of parasitism, the effects of environmental
      contaminants on morphology and sexual function, and comparative neurobiology.
      Ilyanassa is host to several species of parasitic trematode worms, so care must
      be taken to avoid contamination of Ilyanassa genomic DNA with that of the
      parasites. The easiest way to avoid this contamination is to isolate DNA from
      veliger larvae, which are not parasitized. This also avoids other problems that
      can be encountered when isolating DNA from adult mollusc tissues, such as the
      presence of large amounts of polysaccharides. This protocol describes the
      isolation of genomic DNA from Ilyanassa larvae.

PMID- 20147132
TI  - Handling of Helobdella (leech) embryos.
AB  - Gravid Helobdella (leech) adults are identified by white egg masses that are
      visible through the ventral body wall. For convenience, gravid animals should be
      moved to smaller bowls so that those animals with newly laid embryos can be more
      readily identified. Zygotes (fertilized internally) turn pink when they are
      deposited into transparent cocoons on the ventral surface of the parent. A
      typical clutch consists of 20-100 embryos. Embryos can be collected after zygote
      deposition and before hatching (stage 10). This article describes how to collect
      and culture Helobdella embryos.

PMID- 20147131
TI  - Isolating protein from Ilyanassa snail embryos.
AB  - The marine gastropod Ilyanassa obsoleta is a long-standing and very useful model
      for studies of embryonic development. It is an especially important model for
      spiralian development, and for studies of asymmetric cell division. The embryos
      are amenable to classic embryological manipulation techniques as well as a
      growing number of molecular approaches. Ilyanassa is also an important model for
      studies of metamorphosis, the ecology of parasitism, the effects of environmental
      contaminants on morphology and sexual function, and comparative neurobiology.
      This protocol describes the procedure for extracting protein from Ilyanassa
      embryos for use in techniques such as Western blotting or two-dimensional (2D)
      gel electrophoresis.

PMID- 20147133
TI  - Microinjection of Helobdella (leech) embryos.
AB  - One advantage of using Helobdella (leech) embryos as an experimental system is
      their amenability for microinjection. Blastomeres ranging in size from the zygote
      (400 microm diameter) down to micromeres and primary blast cells (approximately
      20 microm diameter) can be injected by pressure under a dissecting microscope.
      Smaller cells can be injected by iontophoresis under a compound microscope.
      Microinjection is useful for studying embryonic development. For example,
      developmental fates of a cell can be followed by injecting a lineage tracer. A
      specific cell can be killed by injecting a toxic substance. Furthermore, cells
      can be killed at a given developmental stage by directing intense fluorescence
      illumination or a blue laser beam on fluorescein-labeled cells. Finally, gene
      expression can be manipulated in leech embryos by injecting zygotes or selected
      blastomeres with synthetic mRNA, morpholino antisense oligo, or a plasmid
      construct. Molecules <1500 Da can diffuse freely among early blastomeres via gap
      junctions. When intercellular diffusion of an injected substance is undesirable,
      small molecules should be conjugated to larger molecules such as dextran (10
      kDa). Different commercial microinjection setups can be adopted for Helobdella
      embryos. This article describes how to microinject embryos using a versatile
      homemade pressure injection system. Under a dissecting microscope, embryos are
      immobilized by suction in a custom-fabricated chamber with the target cell facing
      upward. Cells are visualized using transillumination via a long-working-distance,
      dark-field condenser. The tip of a micropipette is brought into the target cell
      with a micromanipulator, and the injectant is delivered into the cell by
      pressure.

PMID- 20147134
TI  - Devitellinization of living Helobdella (leech) embryos.
AB  - Embryos of glossiphoniid leeches are enclosed in a thin vitelline envelope until
      "hatching" (stage 10). This protocol describes the procedure for removing the
      vitelline envelope from Helobdella robusta and H. sp. (Austin) embryos. This
      protocol is applicable to embryos of stages 1-9 but is probably more useful for
      early stages. With careful culturing, the devitellinized embryos can develop
      normally.

PMID- 20147135
TI  - Arnolds' silver staining of Helbodella (leech) embryos.
AB  - Arnolds' silver staining is used to visualize the boundaries of epidermal cells
      at the surface of embryos. As described in this article, silver staining can be
      performed on either living or fixed Helbodella (leech) embryos. To preserve the
      cell junction in fixed embryos, a special fixation procedure is used.

PMID- 20147136
TI  - Immunostaining Helobdella (leech) embryos.
AB  - The purpose of this staining protocol is to detect the localization of specific
      antigens in the Helobdella (leech) embryo. Immunostaining protocols must be
      optimized for each antibody and embryonic stage. Here, as a starting point, we
      present a general-purpose immunostaining protocol. Immunostaining of the leech
      embryo can be performed on the intact embryo or on dissected parts. For post
      gastrulation embryos (stages 9 and 10), if the area of interest is in the
      germinal plate, immunostaining can be performed on the dissected germinal plate.
      It can also be performed on the ventral nerve cords dissected from late-stage
      embryos or juveniles.

PMID- 20147137
TI  - In situ hybridization of Helobdella (leech) embryos.
AB  - The purpose of this protocol is to reveal the localization of transcripts in the
      Helobdella (leech) embryo. In situ hybridization protocols for Helobdella embryos
      are derived from those used for zebrafish and Xenopus. The protocols are
      different for early- and late-stage embryos (stages 1-8 and stages 9-11,
      respectively) due to a difference in tissue permeability.

PMID- 20147138
TI  - Whole-mount preparation of Helobdella (leech) embryos for microscopy.
AB  - Due to the high yolk content and relatively large size of the Helobdella (leech)
      embryo, it is preferable to examine the embryos in a cleared whole-mount
      preparation after they have been stained. Three whole-mount procedures suitable
      for leech embryos are described here. The glycerol whole mount is quick and
      convenient because it does not require dehydration. However, prolonged incubation
      in buffered glycerol could cause the yolk to turn dark purple. Thus, it is not
      suitable for yolk-containing specimens that are intended for light microscopy.
      For fluorescence microscopy, anti-fading reagent can be added to the buffered
      glycerol. This article includes a recipe that works quite well for leech embryos.
      Also included are two alternative methods that require embryo dehydration, but
      have the advantage of clearing yolk-containing tissue. One method relies on the
      use of benzyl benzoate:benzyl alcohol (BBBA), a solution that provides the best
      clearing of yolk-containing tissue in the leech embryo. It is suitable for both
      fluorescence and light microscopy. Another alternative is the Epon whole-mount
      preparation. Epon is not quite as effective in clearing the yolk, but the
      viscosity of Epon facilitates orienting the specimens for imaging. As with BBBA,
      Epon is suitable for both light and fluorescence microscopy.

PMID- 20147139
TI  - tDNA-PCR followed by automated fluorescent capillary electrophoresis for
      identification of bacterial species.
AB  - Transfer RNA intergenic spacer length polymorphism analysis (tDNA-PCR) is a
      simple and reproducible polymerase chain reaction (PCR) technique for
      identification of bacteria at the species or even subspecies level. The primers
      used in the PCR are based on conserved sequences located at the edges of the tRNA
      genes. Because the selected consensus primers are directed outwardly, the
      intergenic spacers are amplified rather than the genes themselves. With each PCR,
      several amplicons of different lengths are obtained, because several intergenic
      spacers are present in each bacterial genome. The patterns thus obtained are
      identical within species, but differ between distinct species, and as a result,
      can be used for identification of bacterial species. The amplicons are separated
      using high-resolution (1 bp) electrophoresis (e.g., fluorescent capillary
      electrophoresis) and immediately digitized as tables composed of numerical
      lengths (expressed in base pairs) and peak intensities. For identification, the
      resulting peak pattern can be compared with a large database of patterns of well
      identified bacterial strains, using an in-house-developed software package that
      is available online. New patterns (linked to the correct species name, which can
      be obtained, e.g., after 16S rRNA gene sequence determination) can be added to
      expand the database further. This protocol describes tDNA-PCR, followed by
      automated fluorescent capillary electrophoresis to identify bacterial species.

PMID- 20147140
TI  - Enzymatic synthesis of multi-milligram quantities of large, linear DNA molecules
      for structural studies.
AB  - Structural analyses of large protein-DNA complexes (such as those associated with
      replication initiation, eukaryotic transcription activation or chromatin
      remodeling, among others) remain a challenge because of difficulties in obtaining
      multi-milligram quantities of high-quality preparations of large, linear DNA
      molecules. This protocol describes a three-stage DNA amplification procedure for
      making such molecules in amounts that are suitable for structural studies. In the
      first step, conventional polymerase chain reaction (PCR) using specialized primer
      sequences is used to prepare a DNA molecule suitable for self-primed DNA
      synthesis. This molecule, which consists of the sequence of interest flanked by
      the cohesive end sequences from bacteriophage lambda as well as endonuclease
      recognition sites, is then submitted to self-primed DNA synthesis in the second
      step. Amplification produces long polymers of DNA, tens of kilobases in length,
      which harbor many copies of the sequence of interest. The yield from the second
      step is increased in the third phase, which consists of another round of
      amplification. Finally, endonuclease digestion of these polymers, followed by
      chromatographic purification, yields high-quality preparations of DNA. The
      molecules produced by this procedure consist of the DNA sequence of interest with
      three base pairs at either end. This procedure typically yields 400-800 microg of
      purified DNA per milliliter of amplification reaction.

PMID- 20147141
TI  - Quick preparation of genomic DNA from Drosophila.
AB  - This protocol describes a standard miniprep for Drosophila melanogaster that
      requires very few flies and produces high-quality DNA. This method can also be
      used to isolate RNA when RNase-free conditions are utilized; an extra step must
      be taken to rid the sample of genomic DNA (e.g., RNase-free DNase digestion).

PMID- 20147142
TI  - Recovery of DNA sequences flanking P-element insertions in Drosophila: inverse
      PCR and plasmid rescue.
AB  - The Drosophila melanogaster P-transposable element is a powerful and widely used
      research tool. Sequences flanking the P-element can be recovered and the site of
      insertion can be mapped to the nucleotide, to connect the genetic and physical
      maps and facilitate molecular analysis of the gene of interest. The Berkeley
      Drosophila Genome Project (BDGP) has assembled a well-characterized collection of
      lethal mutations induced by single P-element insertions generated by a number of
      laboratories. The genomic DNA sequences adjacent to these insertions have been
      recovered by either plasmid rescue or inverse polymerase chain reaction (PCR).
      The combination of a complete genomic DNA sequence and relatively fast and easy
      molecular methods for mapping P-element insertion sites to the nucleotide
      enhances the use of P-elements as tools in Drosophila research. This protocol
      provides detailed procedures for isolating DNA flanking P-element insertions.

PMID- 20147143
TI  - Dye loading with patch pipettes.
AB  - This protocol describes the loading of individual cells with fluorescent probes
      via patch pipettes. The patch-clamp methodology has been successfully used for
      single-cell dye labeling in cultured neurons, brain slices, and in vivo
      preparations. A broad range of dyes can be used with this loading technique.
      Markers for morphological reconstruction (e.g., Lucifer yellow); ion-sensitive
      indicator dyes for monitoring second-messenger cascades (e.g., fura-2); and dye
      labeled proteins for fluorescence resonance energy transfer (FRET), fluorescence
      correlation spectroscopy (FCS), and fluorescence recovery after photobleaching
      (FRAP) studies are all suitable for patch-clamp loading. The most widespread
      application of this technique has been for Ca(2+) imaging. Whole-cell patch-clamp
      recordings represent a versatile loading technique that allows combined
      electrophysiological and optical measurements at a quantitative level.

PMID- 20147144
TI  - Ballistic delivery of dyes for structural and functional studies of the nervous
      system.
AB  - This protocol describes detailed procedures for rapid labeling of cells in a
      variety of preparations by means of particle-mediated ballistic (i.e., Gene Gun)
      delivery of fluorescent dyes. The method has been used for rapid labeling of
      cells with either lipid- or water-soluble dyes, in a variety of preparations at
      different ages. Tissue preparations include fixed mouse brain slices (described
      here), cell cultures, and tissue explants. This ballistic labeling technique is
      useful for studying neuronal connectivity, function, and pathology in the nervous
      system of living as well as fixed specimens.

PMID- 20147149
TI  - The genus Polypterus (bichirs): a fish group diverged at the stem of ray-finned
      fishes (Actinopterygii).

PMID- 20147150
TI  - The African butterfly Bicyclus anynana: a model for evolutionary genetics and
      evolutionary developmental biology.

PMID- 20147151
TI  - Construction and characterization of adenovirus vectors.

PMID- 20147152
TI  - Microinjection of bichir (Polypterus) embryos.

PMID- 20147153
TI  - Whole-mount in situ hybridization of bichir (Polypterus) embryos.

PMID- 20147154
TI  - Computational docking of biomolecular complexes with AutoDock.

PMID- 20147155
TI  - Culture and propagation of laboratory populations of the African butterfly
      Bicyclus anynana.

PMID- 20147156
TI  - Surgical manipulations on pupal wings from the African butterfly Bicyclus
      anynana: damage and cauteries.

PMID- 20147157
TI  - Surgical manipulations on pupal wings from the African butterfly Bicyclus
      anynana: grafts.

PMID- 20147158
TI  - Fixation and dissection of embryos from the African butterfly Bicyclus anynana.

PMID- 20147159
TI  - Dissection of larval and pupal wings from the African butterfly Bicyclus anynana.

PMID- 20147160
TI  - In situ hybridization of embryos and larval and pupal wings from the African
      butterfly Bicyclus anynana.

PMID- 20147161
TI  - Immunohistochemistry staining of embryos from the African butterfly Bicyclus
      anynana.

PMID- 20147162
TI  - Immunohistochemistry staining of wing discs from the African butterfly Bicyclus
      anynana.

PMID- 20147163
TI  - Extraction and gas chromatography analysis of adult pheromones from the African
      butterfly Bicyclus anynana.

PMID- 20147164
TI  - Fresh weight, dry weight, and fat content of adult African butterflies Bicyclus
      anynana.

PMID- 20147165
TI  - Constant volume respirometry in the African butterfly Bicyclus anynana.

PMID- 20147166
TI  - Hemolymph extraction from various developmental stages of the African butterfly
      Bicyclus anynana.

PMID- 20147167
TI  - Injection of chemicals into pupae of the African butterfly Bicyclus anynana.

PMID- 20147169
TI  - Construction of adenovirus vectors with RGD-modified fiber for transductional
      targeting.

PMID- 20147168
TI  - Preparation and immunolabeling of Caenorhabditis elegans.

PMID- 20147170
TI  - Construction of fusion proteins for transductional targeting.

PMID- 20147171
TI  - Construction of adenovirus vectors for transcriptional targeting.

PMID- 20147172
TI  - Comet fluorescence in situ hybridization (Comet-FISH): detection of DNA damage.

PMID- 20147173
TI  - Systematic monitoring of protein complex composition and abundance by blue-native
      PAGE.

PMID- 20147174
TI  - Metabolic footprinting for the study of microbial biodiversity.

PMID- 20147176
TI  - The honeybee Apis mellifera.

PMID- 20147177
TI  - Selection and evaluation of Tag-SNPs using Tagger and HapMap.

PMID- 20147178
TI  - Counting chromosomes in embryonic stem (ES) cells.

PMID- 20147179
TI  - Labeling mitochondria with fluorescent dyes for imaging.

PMID- 20147180
TI  - Phenotypic analysis of Arabidopsis mutants: diaminobenzidine stain for hydrogen
      peroxide.

PMID- 20147181
TI  - Transcription-based reporters of Wnt/beta-catenin signaling.

PMID- 20147182
TI  - Fixation and storage of honeybee (Apis mellifera) tissues.

PMID- 20147183
TI  - Whole-mount in situ hybridization of honeybee (Apis mellifera) tissues.

PMID- 20147184
TI  - In situ hybridization of sectioned honeybee (Apis mellifera) tissues.

PMID- 20147185
TI  - Immunohistochemistry on honeybee (Apis mellifera) embryos.

PMID- 20147186
TI  - RNA interference (RNAi) in honeybee (Apis mellifera) embryos.

PMID- 20147187
TI  - DNA extraction from forensic samples using chelex.

PMID- 20147188
TI  - Magnetofection: the use of magnetic nanoparticles for nucleic acid delivery.

PMID- 20147189
TI  - Two-photon calcium imaging of spines and dendrites.

PMID- 20147190
TI  - Whole-cell recording and voltage-sensitive dye imaging in vivo.

PMID- 20147191
TI  - Volatile sampling from biological sources by the closed-loop-stripping technique.

PMID- 20147192
TI  - RNA immunoprecipitation to determine RNA-protein associations in vivo.

PMID- 20147193
TI  - Culturing and transfecting zebrafish PAC2 fibroblast cells.

PMID- 20147194
TI  - SIRT combines homologous recombination, site-specific integration, and bacterial
      recombineering for targeted mutagenesis in Drosophila.

PMID- 20147199
TI  - The painted turtle, Chrysemys picta: a model system for vertebrate evolution,
      ecology, and human health.
AB  - Painted turtles (Chrysemys picta) are representatives of a vertebrate clade whose
      biology and phylogenetic position hold a key to our understanding of fundamental
      aspects of vertebrate evolution. These features make them an ideal emerging model
      system. Extensive ecological and physiological research provide the context in
      which to place new research advances in evolutionary genetics, genomics,
      evolutionary developmental biology, and ecological developmental biology which
      are enabled by current resources, such as a bacterial artificial chromosome (BAC)
      library of C. picta, and the imminent development of additional ones such as
      genome sequences and cDNA and expressed sequence tag (EST) libraries. This
      integrative approach will allow the research community to continue making
      advances to provide functional and evolutionary explanations for the lability of
      biological traits found not only among reptiles but vertebrates in general.
      Moreover, because humans and reptiles share a common ancestor, and given the ease
      of using nonplacental vertebrates in experimental biology compared with mammalian
      embryos, painted turtles are also an emerging model system for biomedical
      research. For example, painted turtles have been studied to understand many
      biological responses to overwintering and anoxia, as potential sentinels for
      environmental xenobiotics, and as a model to decipher the ecology and evolution
      of sexual development and reproduction. Thus, painted turtles are an excellent
      reptilian model system for studies with human health, environmental, ecological,
      and evolutionary significance.

PMID- 20147195
TI  - Native chromatin preparation and Illumina/Solexa library construction.

PMID- 20147200
TI  - Ants (Formicidae): models for social complexity.
AB  - The family Formicidae (ants) is composed of more than 12,000 described species
      that vary greatly in size, morphology, behavior, life history, ecology, and
      social organization. Ants occur in most terrestrial habitats and are the dominant
      animals in many of them. They have been used as models to address fundamental
      questions in ecology, evolution, behavior, and development. The literature on
      ants is extensive, and the natural history of many species is known in detail.
      Phylogenetic relationships for the family, as well as within many subfamilies,
      are known, enabling comparative studies. Their ease of sampling and ecological
      variation makes them attractive for studying populations and questions relating
      to communities. Their sociality and variation in social organization have
      contributed greatly to an understanding of complex systems, division of labor,
      and chemical communication. Ants occur in colonies composed of tens to millions
      of individuals that vary greatly in morphology, physiology, and behavior; this
      variation has been used to address proximate and ultimate mechanisms generating
      phenotypic plasticity. Relatedness asymmetries within colonies have been
      fundamental to the formulation and empirical testing of kin and group selection
      theories. Genomic resources have been developed for some species, and a whole
      genome sequence for several species is likely to follow in the near future;
      comparative genomics in ants should provide new insights into the evolution of
      complexity and sociogenomics. Future studies using ants should help establish a
      more comprehensive understanding of social life, from molecules to colonies.

PMID- 20147201
TI  - Comparing programs and methods to use for global multiple sequence alignment.
AB  - It is difficult to find a global optimal alignment of more than two sequences
      (and, especially, more than three) that includes matches, mismatches, and gaps
      and that takes into account the degree of variation in all of the sequences at
      the same time. Thus, approximate methods are used, such as progressive global
      alignment, iterative global alignment, alignments based on locally conserved
      patterns found in the same order in the sequences, statistical methods that
      generate probabilistic models of the sequences, and multiple sequence alignments
      produced by graph-based methods. When 10 or more sequences are being compared, it
      is common to begin by determining sequence similarities between all pairs of
      sequences in the set. A variety of methods are then available to cluster the
      sequences into the most related groups or into a phylogenetic tree. This article
      discusses several of these methods and provides data that compare their utility
      under various conditions.

PMID- 20147202
TI  - Phenotypic analysis of Arabidopsis mutants: bacterial pathogens.
AB  - The most commonly used bacterial pathogen of Arabidopsis is Pseudomonas syringae,
      pathovar tomato strain DC3000 or pathovar maculicola strain ES4326. Plants used
      for infection with P. syringae should be grown on a short-day light cycle, so
      that they develop large leaves. For consistent results, it is important that the
      plants are watered well and do not experience any abiotic stresses. The plants
      should be grown and tested in a temperature- and humidity-controlled growth
      chamber, because the extent of bacterial growth is highly dependent on both
      factors. Gene-for-gene resistance to P. syringae is usually accompanied by the
      hypersensitive response (HR), a form of localized cell death that occurs in
      response to pathogen challenge. P. syringae strains carrying one of the
      avirulence genes avrRpt2, avrRpm1, avrB, avrPphB, and avrRps4 trigger the HR in
      wild-type Columbia. Other ecotypes may lack one or more of the R genes needed for
      recognition of these avirulence genes. Bacterial growth can be monitored by
      grinding up infected tissue, plating serial dilutions on King's B medium, and
      counting colonies. This protocol describes methods for preparing bacterial
      cultures, inoculating plants, testing the HR, and assessing bacterial growth.

PMID- 20147203
TI  - Egg incubation and collection of painted turtle embryos.
AB  - This protocol describes how to incubate painted turtle eggs and collect embryos
      for gene expression analysis. The same basic protocol can be used to incubate
      eggs and collect embryos from other turtle species by modifying the incubation
      temperature to suit the particular developmental needs of each species.

PMID- 20147204
TI  - Collecting live ant specimens (colony sampling).
AB  - Because of the great diversity of ants, it is difficult to give a single protocol
      for the collection of live specimens. Ant body size can be very small or
      extremely large; the ants can be hard or soft, sting or spray toxic chemicals,
      live in the open or in hard-to-reach places; and colony size can range from tens
      of individuals to millions. Thus, collection techniques must be tailored to each
      particular species. In particular, caution must always be taken when dealing with
      stinging species, and symptoms and basic first-aid measures, especially for the
      treatment of anaphylactic shock, should be reviewed before beginning fieldwork.
      Nonetheless, many species are collectable as whole colonies. This protocol
      reviews some basic techniques for collecting ground-nesting species and describes
      how to collect whole live colonies (with queens), which are necessary for long
      term laboratory studies and addressing questions of social organization and
      ecology.

PMID- 20147205
TI  - Marking individual ants for behavioral sampling in a laboratory colony.
AB  - Ant societies are tractable and malleable, two features that make them ideal
      models for probing the organization of complex biological systems. The ability to
      identify specific individuals while they function as part of a colony permits an
      integrative analysis of social complexity, including self-organizational
      processes (i.e., how individual-level properties and social interactions give
      rise to emergent, colony-level attributes such as division of labor and
      collective decision making). Effects of genotype, nutrition, and physiology on
      individual behavior and the organization of work also can be investigated in this
      manner, through correlative and manipulative approaches. Moreover, aspects of
      colony demography (e.g., colony size, and age and size distributions of workers)
      can be altered experimentally to examine colony development and regulatory
      mechanisms underlying colony homeostasis and resiliency. This protocol describes
      how to sample the behavior of ants living in a colony under laboratory
      conditions. Specifically, it outlines how to identify and observe individuals
      within a colony, an approach that can be used to quantify individual- and colony
      level patterns of behavior. When a lower-resolution measure of overall group
      behavior is desired, individual identities might not be required. Given the
      diversity of ants and their study, this protocol provides a very general
      methodology; the details can be modified according to the body size, colony size,
      and ecology of the focal species, as well as to specific research aims. These
      basic techniques can also be extended to more advanced experimental designs such
      as manipulation of colony demography and hormone treatment.

PMID- 20147206
TI  - Ecological sampling of ants: competition and biodiversity.
AB  - Ants are among the most dominant taxa in terrestrial ecosystems, despite their
      small individual size. Furthermore, they are a hyperdiverse family with an
      estimated 20,000 species. Together, these two properties make ants a model for
      ecological interactions (specifically competition) and biodiversity estimation.
      Although there are many means of measuring diversity, the two most common among
      myrmecologists are baiting and pitfall trapping. Pitfall traps provide an almost
      unbiased estimate of the ground foraging community, whereas baiting allows the
      estimation of ecological dominance and the competitive outcomes between species.
      This protocol describes an approach to assay both abundance (pitfall traps) and
      ecological interactions (baits) in the same community.

PMID- 20147207
TI  - Stable isotope and elemental analysis in ants.
AB  - Over the past 20 yr, the use of stable isotopes to infer feeding ecology and the
      examination of how energetic and elemental exchanges are affected by and affect
      life (ecological stoichiometry) have gained momentum. The ecological diversity of
      ants makes them interesting models to explore dietary ecology and their role in
      food webs. Moreover, their ecological dominance in most habitats facilitates
      sampling. The protocol described here will produce samples adequate for
      submission to most labs that specialize in high-throughput analysis of stable
      isotopes; one should check with any particular lab for specific submission
      instructions. Note, however, that this protocol is designed specifically for the
      quantification of the natural abundance of stable isotopes; it does not cover the
      preparation of trace samples.

PMID- 20147208
TI  - Ant fat extraction with a Soxhlet extractor.
AB  - Stored fat can be informative about the relative age of an ant, its nutritional
      status, and the nutritional status of the colony. Several methods are available
      for the quantification of stored fat. Before starting a project involving fat
      extraction, investigators should weigh the advantages and disadvantages of
      different methods in order to choose the one that is best suited to the question
      being addressed. This protocol, although not as accurate as some alternatives,
      facilitates the rapid quantification of many individuals.

PMID- 20147209
TI  - General dissection of female ant reproductive system and brain.
AB  - Dissection of the reproductive system of ant workers and queens can be useful for
      answering many questions. Observations of ovarian status in both female castes
      can be used to identify relationships between other factors and the ovaries,
      determine whether an individual has laid eggs, and, with more advanced molecular
      techniques, identify the end product of the oocyte in question (e.g., trophic
      egg, viable egg, nonviable egg). In addition, dissection of queens allows for
      observation of the spermatheca (the sperm storage organ), and thus identification
      of whether an individual has mated. Sperm can also be sampled for genetic
      analyses. In this protocol, we describe the dissection of the female ant
      reproductive system. We also discuss dissection of the corpora allata glands,
      where juvenile hormone is produced.

PMID- 20147210
TI  - DNA isolation from ants.
AB  - Many different DNA isolation methods have been employed successfully in ants.
      Parameters such as the size and developmental stage of the specimen (egg, larvae,
      or adult) and the subsequent use of the DNA will mostly determine which method
      should be used. Ant body sizes range from minute (1-2 mm in length) to large (30
      mm), and the volume of the initial digestion should be adjusted accordingly.
      Whereas workers usually have low concentrations of storage proteins and fat,
      queens and larvae can contain considerable amounts of these substances that can
      interfere with the subsequent use of the isolated DNA. Ants also have many glands
      in the head and abdomen, and the contents of these glands can also interfere with
      the successful application of polymerase chain reaction (PCR) or restriction
      digests of the isolated DNA. This protocol presents two DNA isolation methods
      that have worked reliably for a wide range of ant species: a "quick and dirty"
      technique using Chelex isolation, and a more elaborate, classical
      phenol:chloroform procedure.

PMID- 20147211
TI  - Juvenile hormone extraction, purification, and quantification in ants.
AB  - Juvenile hormone (JH) is an important insect hormone known to have many effects
      on development, reproduction, and behavior in both solitary and social insects. A
      number of questions using ants as a model involve JH. This procedure allows for
      quantification of circulating levels of JH III, which can be an important factor
      in many questions relating to insect research. The JH III is extracted from a
      subject, purified, and converted to a d(3)-methoxyhydrin derivative that can be
      quantified by gas chromatography-mass spectrometry (GC-MS). The major advantages
      of this protocol are its high resolution, and its ability to quantify significant
      differences between relatively small quantities of the hormone. Its major
      limitations are the time necessary to process samples, its relatively high cost,
      and maintaining the sensitivity of the equipment.

PMID- 20147212
TI  - Ant ecdysteroid extraction and radioimmunoassay.
AB  - Ecdysteroids are a group of steroid compounds present in many plant and
      invertebrate species. In arthropods, they function primarily as hormones involved
      in the regulation of molting. This protocol describes how to extract ecdysteroid
      hormones from ant specimens and subsequently quantify circulating levels of the
      hormone. The hormone can be extracted from hemolymph or from whole-body
      homogenates of insects and quantified by radioimmunoassay.

PMID- 20147213
TI  - Radiochemical assay of juvenile hormone biosynthesis rate in ants.
AB  - Juvenile hormone (JH) is an important insect hormone known to have many effects
      on development, reproduction, and behavior in both solitary and social insects.
      This protocol describes how to quantify in vitro biosynthesis rates from excised
      corpora allata (CA), the glands responsible for JH production. Excised glands are
      incubated with radiolabeled methionine, resulting in the production of
      radiolabeled JH III, which can then be quantified. This protocol is most useful
      when quantification of the activity of the glands, rather than circulating JH
      levels, is desired. Its difficulties lie primarily in the ability to remove and
      handle the glands correctly.

PMID- 20147214
TI  - GC-MS for characterization and identification of ant semiochemicals.
AB  - Living in a predominantly dark environment, ants rely mostly on chemical signals
      for communication. Trail and alarm pheromones are the most widely studied and
      best characterized of all ant semiochemicals, but other such compounds can
      influence a variety of other behaviors, including reproductive activities, sexual
      development, nest mate and caste recognition, and defense. A typical worker body
      contains more than 10 different semiochemical-producing glands, and the surface
      of the cuticle is covered with lipids that serve as recognition signals. The
      methods of choice for collection and identification of ant semiochemicals should
      be determined based on results of behavioral analyses. These can indicate the
      source (e.g., glandular, cuticular) and the nature (volatile vs. nonvolatile) of
      the chemical. This protocol presents a number of different methods for collecting
      lipid semiochemicals. These can be followed by gas chromatography (GC) coupled
      with mass spectrometry (MS) to better characterize, and possibly identify, the
      semiochemical in question.

PMID- 20147215
TI  - In situ hybridization on ant ovaries and embryos.
AB  - The detection of transcript distribution throughout a fixed tissue is a major
      step in studying the transcriptional activity of target genes and their function.
      In situ hybridization specifically detects the spatial distribution of RNA
      transcripts using an antisense RNA probe. This protocol describes the preparation
      of digoxigenin-labeled antisense RNA probes and their hybridization to
      complementary mRNA sequences; expression can then be localized using an antibody
      against digoxigenin conjugated to a chromogenic enzyme. In ants, this method can
      be applied to visualize cell populations of interest among other populations in a
      tissue, such as insect ovaries, or in the whole organism, such as insect embryos.
      Specific markers (e.g., genes known to be expressed in particular clusters of
      cells) can be cloned and used as probes to study the distribution and development
      of germline cells (e.g., nanos, vasa), neurons (repo), or limb structures (e.g.,
      distal-less). Various markers might also allow the study of oogenesis (nanos, par
      1, oskar), segmentation in the embryo (e.g., engrailed, wingless), or other
      developmental processes.

PMID- 20147216
TI  - Phase-unknown linkage mapping in ants.
AB  - To create a genetic linkage map of an ant genome, the phase of a marker (i.e.,
      which marker/allele came from the grandmother and which came from the grandfather
      of the individuals used for linkage mapping) must be known. However, field
      colonies contain only two generations: the queen(s) and their offspring.
      Normally, virgin queens disperse from their nest, mate with one or multiple males
      who die after mating, and start a new colony. A new reproductive brood (i.e.,
      virgin queens and males) is usually produced after colony establishment, which
      can take from 6 mo to 3-5 yr. Hence, determining the phase of markers from field
      samples is impossible because the grandparents of a reproductive queen are no
      longer available for genetic analysis. Ants raised in the laboratory are likewise
      unsuitable for such analyses, because most ants cannot be bred regularly in the
      laboratory, and attempts to inseminate ant queens artificially have not been
      successful. However, three features facilitate "phase-unknown" linkage mapping
      for any ant (or other social hymenopteran) species, which is described here: (1)
      Mature colonies usually produce many reproductive offspring during a short period
      of time, which allows for the collection of a good-sized mapping population (>100
      males) from a field colony; (2) Ants have a haplodiploid sex determination system
      (i.e., males are haploid and females diploid); (3) Queens produce males
      parthenogenetically. Thus, because they have no father, only those markers for
      which the queen is heterozygous are expected to segregate 1:1 in her male
      offspring.

PMID- 20147217
TI  - Nested Patch PCR for highly multiplexed amplification of genomic loci.
AB  - Nested Patch polymerase chain reaction (PCR) amplifies a large number (greater
      than 90) of targeted loci from genomic DNA simultaneously in the same reaction.
      These amplified loci can then be sequenced on a second-generation sequencing
      machine to detect single nucleotide polymorphisms (SNPs) and mutations. The
      reaction is highly specific: 90% of sequencing reads match targeted loci. Nested
      Patch PCR can be performed on many samples in parallel, and by using sample
      specific DNA barcodes, these can be pooled and sequenced in a single reaction.
      Thus, the Nested Patch PCR protocol that is described here provides an easy
      workflow to identify SNPs and mutations across many targeted loci for many
      samples in parallel.

PMID- 20147218
TI  - Use of fluorescence in situ hybridization and the daime image analysis program
      for the cultivation-independent quantification of microorganisms in environmental
      and medical samples.
AB  - Conventional cultivation-based methods to measure microbial abundance are
      unsuitable for quantifying uncultured microorganisms that constitute the majority
      of microbial life in most environmental or medical samples. This problem is
      solved by the quantification approach described here, which combines fluorescence
      in situ hybridization (FISH) with rRNA-targeted probes and digital image
      analysis. By measuring the areas of probe-labeled biomass in randomly recorded
      image pairs, an unbiased estimate of the relative biovolume of the population of
      interest can be obtained. This approach expresses abundance as "biovolume
      fraction" (relative to the total biovolume of the whole microbial community).
      This value equals the share of biochemical reaction space occupied by the
      quantified population and thus can be more relevant ecologically than absolute
      cell numbers (e.g., a few large cells can contain the same biovolume as many
      small cells). Another advantage lies in the complete independence of this method
      from the morphology of the quantified organisms. Regardless of whether the target
      microbes occur as single cells in plankton samples, as filaments, or as dense
      aggregates in biofilms, this cultivation-independent method allows the
      composition of complex microbial communities to be determined.

PMID- 20147219
TI  - Preparation of high-molecular-weight DNA from Drosophila embryos.
AB  - Standard methods for extracting DNA from cells or organisms (e.g., phenol
      extraction and ethanol precipitation) produce fragments with an average size of
      50-200 kb under optimal conditions. The shearing forces that are applied to DNA
      in solution during mechanical vortexing or mixing and pipetting produce frequent
      double-stranded breaks. To prepare high-molecular-weight (HMW) DNA, it is
      necessary to guard against such damaging forces by performing all extractions and
      manipulations on DNA that is embedded within a protective matrix. Preparation of
      HMW DNA from Drosophila embryos is described in detail here because, in our
      hands, it is the simplest and most reliable protocol and can be used for large-
      or small-scale preparations. The overall strategy is to purify nuclei, gently
      embed them in molten agarose, and then extract proteins and perform other
      enzymatic reactions by transferring the solidified agarose block into the
      appropriate solutions. Salts, soaps, and enzymes act on the DNA by diffusing
      through the agarose matrix, while the matrix protects the DNA from shearing
      forces.

PMID- 20147220
TI  - Adhesive micropatterns for cells: a microcontact printing protocol.
AB  - This protocol describes a simple, fast, and efficient method for making adhesive
      micropatterns that can be used to control individual cell shape and adhesion
      patterns. It is based on the use of an elastomeric stamp containing microfeatures
      to print proteins on the substrate of choice. The process can be subdivided into
      three parts. First, a silicon master is fabricated, which contains the
      microfeatures of interest. Once fabricated, the master can be used multiple times
      to make stamps. Masters with customized patterns can also be purchased
      commercially. Second, a polydimethylsiloxane (PDMS) stamp is fabricated. Unlike
      fabrication of the master, this step can be performed without specialized
      equipment. The PDMS stamp is inked with extracellular matrix proteins. Proteins
      are printed on a substrate (e.g., a tissue culture polystyrene dish or a glass
      coverslip covered with a thin layer of polystyrene). The nonprinted areas are
      back-filled with poly-L-lysine-polyethylene glycol, which renders them resistant
      to cell adhesion. The production of these micropatterned substrates can be
      completed in <2 h. The third and final portion of the protocol describes the
      deposition of cells onto the micropatterned substrate.

PMID- 20147223
TI  - Using hidden Markov models to align multiple sequences.
AB  - A hidden Markov model (HMM) is a probabilistic model of a multiple sequence
      alignment (msa) of proteins. In the model, each column of symbols in the
      alignment is represented by a frequency distribution of the symbols (called a
      "state"), and insertions and deletions are represented by other states. One moves
      through the model along a particular path from state to state in a Markov chain
      (i.e., random choice of next move), trying to match a given sequence. The next
      matching symbol is chosen from each state, recording its probability (frequency)
      and also the probability of going to that state from a previous one (the
      transition probability). State and transition probabilities are multiplied to
      obtain a probability of the given sequence. The hidden nature of the HMM is due
      to the lack of information about the value of a specific state, which is instead
      represented by a probability distribution over all possible values. This article
      discusses the advantages and disadvantages of HMMs in msa and presents algorithms
      for calculating an HMM and the conditions for producing the best HMM.

PMID- 20147224
TI  - Using progressive methods for global multiple sequence alignment.
AB  - Finding a global optimal alignment of more than two sequences that includes
      matches, mismatches, and gaps and that takes into account the degree of variation
      in all of the sequences at the same time is especially difficult. The dynamic
      programming algorithm used for optimal alignment of pairs of sequences can be
      extended to global alignment of three sequences, but for more than three
      sequences, only a small number of relatively short sequences may be analyzed.
      Thus, approximate methods are used for global sequence alignment. One class of
      these methods is progressive global alignment, which starts with an alignment of
      the most alike sequences and then builds an alignment by adding more sequences.
      This article introduces three programs that use progressive alignment
      methodology.

PMID- 20147225
TI  - Using iterative methods for global multiple sequence alignment.
AB  - Finding a global optimal alignment of more than two sequences that includes
      matches, mismatches, and gaps and that takes into account the degree of variation
      in all of the sequences at the same time is especially difficult. The dynamic
      programming algorithm used for optimal alignment of pairs of sequences can be
      extended to global alignment of three sequences, but for more than three
      sequences, only a small number of relatively short sequences may be analyzed.
      Thus, approximate methods are used for global alignment. One class of these is
      iterative global alignment, which makes an initial global alignment of groups of
      sequences and then revises the alignment to achieve a more reasonable result.
      This article discusses several iterative alignment methods. In particular, steps
      are provided for using the Sequence Alignment by Genetic Algorithm (SAGA).

PMID- 20147226
TI  - Using multiple sequence alignment editors and formatters.
AB  - Sequence alignment editors enable the user to manually edit a multiple sequence
      alignment (msa) in order to obtain a more reasonable or expected alignment.
      Editors allow sequences to be reordered and/or modified using the computer's cut
      and paste commands. They are designed to accept various msa formats and to
      provide the output file in a suitable user-designated format. Sequence formatters
      provide various output formatting options, such as color and shading schemes to
      enhance visualization of residue alignments. The formatters can output files in
      Postscript, EPS, RTF, and other widely recognized formats, while accepting the
      standard input formats, such as MSF, ALN, and FASTA. This article introduces a
      number of sequence alignment editors and formatters, and provides links to sites
      where they can be found.

PMID- 20147227
TI  - Indicators based on fluorescence resonance energy transfer (FRET).
AB  - One of the major new trends in the design of indicators for optically imaging
      biochemical and physiological functions of living cells has been the exploitation
      of fluorescence resonance energy transfer (FRET). FRET is a well-known
      spectroscopic technique for monitoring changes in the proximity and mutual
      orientation of pairs of chromophores. It has long been used in biochemistry and
      cell biology to assess distances and orientations between specific labeling sites
      within a single macromolecule or between two separate molecules. More recently,
      macromolecules or molecular pairs have been engineered to change their FRET in
      response to biochemical and physiological signals such as membrane potential,
      cyclic AMP (cAMP), protease activity, free Ca(2+) and Ca(2+)-calmodulin (CaM)
      concentrations, protein-protein heterodimerization, phosphorylation, and reporter
      gene expression. Because FRET is general, nondestructive, and easily imaged, it
      has proven to be one of the most versatile spectroscopic readouts available to
      the designer of new probes. FRET is particularly amenable to emission ratioing,
      which is more reliably quantifiable than single-wavelength monitoring and better
      suited than excitation ratioing to high-speed and laser-excited imaging. This
      article summarizes the photophysical principles of FRET and the types of
      indicators used.

PMID- 20147228
TI  - The red flour beetle, Tribolium castaneum (Coleoptera): a model for studies of
      development and pest biology.

PMID- 20147229
TI  - Morphology and husbandry of the large milkweed bug, Oncopeltus fasciatus.

PMID- 20147230
TI  - Ambystoma mexicanum, the axolotl: a versatile amphibian model for regeneration,
      development, and evolution studies.

PMID- 20147231
TI  - Strategies for cloning PCR products.

PMID- 20147232
TI  - RNAi in the red flour beetle (Tribolium).

PMID- 20147233
TI  - Concurrent in situ hybridization and antibody staining in red flour beetle
      (Tribolium) embryos.

PMID- 20147234
TI  - Single and double whole-mount in situ hybridization in red flour beetle
      (Tribolium) embryos.

PMID- 20147235
TI  - Red flour beetle (Tribolium) germline transformation and insertional mutagenesis.

PMID- 20147236
TI  - Analyzing microarray data using WebArray.

PMID- 20147237
TI  - Dissection and fixation of large milkweed bug (Oncopeltus) embryos.

PMID- 20147238
TI  - In situ hybridization of large milkweed bug (Oncopeltus) tissues.

PMID- 20147240
TI  - Generation of transgenic axolotls (Ambystoma mexicanum).

PMID- 20147239
TI  - Axolotl (Ambystoma mexicanum) in vitro fertilization.

PMID- 20147241
TI  - Axolotl (Ambystoma mexicanum) embryonic transplantation methods.

PMID- 20147243
TI  - Axolotl (Ambystoma mexicanum) limb and tail amputation.

PMID- 20147242
TI  - Grafting axolotl (Ambystoma mexicanum) limb skin and cartilage from GFP+ donors
      to normal hosts.

PMID- 20147244
TI  - Induction of metamorphosis in axolotls (Ambystoma mexicanum).

PMID- 20147245
TI  - Chromosome orientation fluorescence in situ hybridization (CO-FISH).

PMID- 20147246
TI  - Use of the Sleeping Beauty transposon system for stable gene expression in mouse
      embryonic stem cells.

PMID- 20147248
TI  - Preparation of coverslips for neuronal cultures.

PMID- 20147249
TI  - Dissection, plating, and maintenance of cortical astrocyte cultures.

PMID- 20147247
TI  - Isolation and cloning of high-molecular-weight metagenomic DNA from soil
      microorganisms.

PMID- 20147250
TI  - Dissection, plating, and maintenance of dorsal horn neuron cultures.

PMID- 20147251
TI  - Dissection, plating, and maintenance of dorsal root ganglion neurons for
      monoculture and for coculture with dorsal horn neurons.

PMID- 20147255
TI  - Assessing significance in genetic association studies.

PMID- 20147256
TI  - Engineering the surface glycoproteins of lentiviral vectors for targeted gene
      transfer.

PMID- 20147252
TI  - Hematopoietic stem cell targeting with surface-engineered lentiviral vectors.

PMID- 20147257
TI  - The starlet sea anemone Nematostella vectensis: an anthozoan model organism for
      studies in comparative genomics and functional evolutionary developmental
      biology.

PMID- 20147258
TI  - Cephalochordates (amphioxus or lancelets): a model for understanding the
      evolution of chordate characters.

PMID- 20147259
TI  - The western clawed frog (Xenopus tropicalis): an emerging vertebrate model for
      developmental genetics and environmental toxicology.

PMID- 20147260
TI  - In vivo imaging of mammalian cells: cell engineering and viability.

PMID- 20147261
TI  - In vivo imaging of mammalian cells: image acquisition and analysis.

PMID- 20147262
TI  - In vivo DNase I, MNase, and restriction enzyme footprinting via ligation-mediated
      polymerase chain reaction (LM-PCR).

PMID- 20147263
TI  - In vivo dimethyl sulfate (DMS) footprinting via ligation-mediated polymerase
      chain reaction (LM-PCR).

PMID- 20147264
TI  - Chromatin immunoprecipitation (ChIP).

PMID- 20147265
TI  - Position-based clustering of microarray expression data.

PMID- 20147266
TI  - Induction of spawning in the starlet sea anemone Nematostella vectensis, in vitro
      fertilization of gametes, and dejellying of zygotes.

PMID- 20147267
TI  - In situ hybridization of starlet sea anemone (Nematostella vectensis) embryos,
      larvae, and polyps.

PMID- 20147268
TI  - Anti-acetylated tubulin antibody staining and phalloidin staining in the starlet
      sea anemone Nematostella vectensis.

PMID- 20147269
TI  - Bromodeoxyuridine labeling of S-phase nuclei in the starlet sea anemone
      Nematostella vectensis.

PMID- 20147270
TI  - Amphioxus (Branchiostoma floridae) spawning and embryo collection.

PMID- 20147271
TI  - Amphioxus whole-mount in situ hybridization.

PMID- 20147272
TI  - Extraction of DNA from adult amphioxus tissue.

PMID- 20147273
TI  - Extraction of RNA from amphioxus embryos or adult amphioxus tissue.

PMID- 20147275
TI  - Fluorescent in situ hybridization (FISH) on diploid nuclei and mitotic
      chromosomes from Drosophila melanogaster larval tissues.

PMID- 20147274
TI  - Extraction of RNA from small amounts of amphioxus embryos for cDNA synthesis by
      RT-PCR.

PMID- 20147276
TI  - Construction of gene-targeting vectors by recombineering.

PMID- 20147277
TI  - Natural mating and tadpole husbandry in the western clawed frog Xenopus
      tropicalis.

PMID- 20147278
TI  - Egg collection and in vitro fertilization of the western clawed frog Xenopus
      tropicalis.

PMID- 20147280
TI  - RNA extraction from Arabidopsis for Northern blots and reverse transcriptase-PCR.

PMID- 20147279
TI  - Tissue sampling and genomic DNA purification from the western clawed frog Xenopus
      tropicalis.

PMID- 20147281
TI  - Semiquantitative analysis of Arabidopsis RNA by reverse transcription followed by
      noncompetitive PCR.

PMID- 20147282
TI  - Semiquantitative analysis of Arabidopsis RNA by reverse transcription followed by
      PCR using mimics.

PMID- 20147284
TI  - Comment on 'Membranous glomerulonephritis secondary to Borrelia burgdorferi
      infection presenting as nephrotic syndrome'.

PMID- 20147285
TI  - Studies of the maltose transport system reveal a mechanism for coupling ATP
      hydrolysis to substrate translocation without direct recognition of substrate.
AB  - The ATPase activity of the maltose transporter (MalFGK(2)) is dependent on
      interactions with the maltose-binding protein (MBP). To determine whether direct
      interactions between the translocated sugar and MalFGK(2) are important for the
      regulation of ATP hydrolysis, we used an MBP mutant (sMBP) that is able to bind
      either maltose or sucrose. We observed that maltose- and sucrose-bound sMBP
      stimulate equal levels of MalFGK(2) ATPase activity. Therefore, the ATPase
      activity of MalFGK(2) is coupled to translocation of maltose solely by
      interactions between MalFGK(2) and MBP. For both maltose and sucrose, the ability
      of sMBP to stimulate the MalFGK(2) ATPase was greatly reduced compared with wild
      type MBP, indicating that the mutations in sMBP have interfered with important
      interactions between MBP and MalFGK(2). High resolution crystal structure
      analysis of sMBP shows that in the closed conformation with bound sucrose, three
      of four mutations are buried, and the fourth causes only a minor change in the
      accessible surface. In contrast, in the open form of sMBP, all of the mutations
      are accessible, and the main chain of Tyr(62)-Gly(69) is destabilized and
      occupies an alternative conformation due to the W62Y mutation. On this basis, the
      compromised ability of sMBP to stimulate ATP hydrolysis by MalFGK(2) is most
      likely due to a disruption of interactions between MalFGK(2) and the open, rather
      than the closed, conformation of sMBP. Modeling the open sMBP structure bound to
      MalFGK(2) in the transition state for ATP hydrolysis points to an important site
      of interaction and suggests a mechanism for coupling ATP hydrolysis to substrate
      translocation that is independent of the exact structure of the substrate.

PMID- 20147286
TI  - Transmembrane segment 3 of Drosophila melanogaster odorant receptor subunit 85b
      contributes to ligand-receptor interactions.
AB  - The OR class insect odorant receptors are ligand-gated ion channels comprised of
      at least one common subunit (OR83b in Drosophila) and at least one putative
      odorant-binding subunit. However, little else is known about the molecular
      details of insect OR architecture. For example, nothing is known about how these
      receptors bind odorants, greatly limiting efforts to develop insect OR-targeted
      compounds for the control of insects involved in disease propagation and
      agricultural damage. Here we identify a portion of a Drosophila OR that is
      involved in odorant activation of the receptor. Using the substituted cysteine
      accessibility method, we identified residues 146-150 of OR85b, located at the
      predicted interface between transmembrane segment 3 (TMS3) and extracellular loop
      2 (ECL2), as playing a role in odorant (2-heptanone) activation. We found that
      occupation of the receptor by the competitive antagonist 2-nonanone protected the
      receptor from methanethiosulfonate action at position 148, placing this region
      close to the odorant-binding site. In addition, mutations at positions 142 and
      143 within TMS3 altered odorant sensitivity. Our results identify the involvement
      of the extracellular half of TMS3 in Drosophila OR85b in odorant activation of
      the receptor. This finding can serve as a starting point for future detailed
      analysis of the molecular basis for odorant recognition by insect ORs, a novel
      class of ligand-gated channel.

PMID- 20147288
TI  - Targeting acetylcholinesterase to membrane rafts: a function mediated by the
      proline-rich membrane anchor (PRiMA) in neurons.
AB  - In the mammalian brain, acetylcholinesterase (AChE) is anchored in cell membranes
      by a transmembrane protein PRiMA (proline-rich membrane anchor). We present
      evidence that at least part of the PRiMA-linked AChE is integrated in membrane
      microdomains called rafts. A significant proportion of PRiMA-linked AChE
      tetramers from rat brain was recovered in raft fractions; this proportion was
      markedly higher at low rather than at high concentrations of cold Triton X-100.
      The detergent-resistant fraction increased during brain development. In NG108-15
      neuroblastoma cells transfected with cDNAs encoding AChE(T) and PRiMA, PRiMA
      linked G(4) AChE was found in membrane rafts and showed the same sensitivity to
      cold Triton X-100 extraction as in the brain. The association of PRiMA-linked
      AChE with rafts was weaker than that of glycosylphosphatidylinositol-anchored
      G(2) AChE or G(4) Q(N)-H(C)-linked AChE. It was found to depend on the presence
      of a cholesterol-binding motif, called CRAC (cholesterol recognition/interaction
      amino acid consensus), located at the junction of transmembrane and cytoplasmic
      domains of both PRiMA I and II isoforms. The cytoplasmic domain of PRiMA, which
      differs between PRiMA I and PRiMA II, appeared to play some role in stabilizing
      the raft localization of G(4) AChE, because the Triton X-100-resistant fraction
      was smaller with the shorter PRiMA II isoform than that with the longer PRiMA I
      isoform.

PMID- 20147287
TI  - The Staphylococcus aureus siderophore receptor HtsA undergoes localized
      conformational changes to enclose staphyloferrin A in an arginine-rich binding
      pocket.
AB  - Staphylococcus aureus uses several efficient iron acquisition strategies to
      overcome iron limitation. Recently, the genetic locus encoding biosynthetic
      enzymes for the iron chelating molecule, staphyloferrin A (SA), was determined.
      S. aureus synthesizes and secretes SA into its environment to scavenge iron. The
      membrane-anchored ATP binding cassette-binding protein, HtsA, receives the ferric
      chelate for import into the cell. Recently, we determined the apoHtsA crystal
      structure, the first siderophore receptor from gram-positive bacteria to be
      structurally characterized. Herein we present the x-ray crystal structure of the
      HtsA-ferric-SA complex. HtsA adopts a class III binding protein fold composed of
      separate N- and C-terminal domains bridged by a single alpha-helix. Recombinant
      HtsA can efficiently sequester ferric-SA from S. aureus culture supernatants
      where it is bound within the pocket formed between distinct N- and C-terminal
      domains. A basic patch composed mainly of six Arg residues contact the negatively
      charged siderophore, securing it within the pocket. The x-ray crystal structures
      from two different ligand-bound crystal forms were determined. The structures
      represent the first structural characterization of an endogenous alpha
      hydroxycarboxylate-type siderophore-receptor complex. One structure is in an open
      form similar to apoHtsA, whereas the other is in a more closed conformation. The
      conformational change is highlighted by isolated movement of three loops within
      the C-terminal domain, a domain movement unique to known class III binding
      protein structures.

PMID- 20147289
TI  - Stability and assembly of pilus subunits of Streptococcus pneumoniae.
AB  - Pili are surface-exposed virulence factors involved in bacterial adhesion to host
      cells. The Streptococcus pneumoniae pilus is composed of three structural
      proteins, RrgA, RrgB, and RrgC and three transpeptidase enzymes, sortases SrtC-1,
      SrtC-2, and SrtC-3. To gain insights into the mechanism of pilus formation we
      have exploited biochemical approaches using recombinant proteins expressed in
      Escherichia coli. Using site-directed mutagenesis, mass spectrometry, limited
      proteolysis, and thermal stability measurements, we have identified isopeptide
      bonds in RrgB and RrgC and demonstrate their role in protein stabilization. Co
      expression in E. coli of RrgB together with RrgC and SrtC-1 leads to the
      formation of a covalent RrgB-RrgC complex. Inactivation of SrtC-1 by mutation of
      the active site cysteine impairs RrgB-RrgC complex formation, indicating that the
      association between RrgB and RrgC is specifically catalyzed by SrtC-1. Mass
      spectrometry analyses performed on purified samples of the RrgB-RrgC complex show
      that the complex has 1:1 stoichiometry. The deletion of the IPQTG RrgB sorting
      signal, but not the corresponding sequence in RrgC, abolishes complex formation,
      indicating that SrtC-1 recognizes exclusively the sorting motif of RrgB. Finally,
      we show that the intramolecular bonds that stabilize RrgB may play a role in its
      efficient recognition by SrtC-1. The development of a methodology to generate
      covalent pilin complexes in vitro, facilitating the study of sortase specificity
      and the importance of isopeptide bond formation for pilus biogenesis, provide key
      information toward the understanding of this complex macromolecular process.

PMID- 20147290
TI  - The role and structure of the carboxyl-terminal domain of the human voltage-gated
      proton channel Hv1.
AB  - The voltage-gated proton channel Hv1 has a voltage sensor domain but lacks a pore
      domain. Although the C-terminal domain of Hv1 is known to be responsible for
      dimeric architecture of the channel, its role and structure are not known. We
      report that the full-length Hv1 is mainly localized in intracellular compartment
      membranes rather than the plasma membrane. Truncation of either the N or C
      terminus alone or both together revealed that the N-terminal deletion did not
      alter localization, but deletion of the C terminus either alone or together with
      the N terminus resulted in expression throughout the cell. These results indicate
      that the C terminus is essential for Hv1 localization but not the N terminus. In
      the 2.0 A structure of the C-terminal domain, the two monomers form a dimer via a
      parallel alpha-helical coiled-coil, in which one chloride ion binds with the Neta
      atom of Arg(264). A pH-dependent structural change of the protein has been
      observed, but it remains a dimer irrespective of pH value.

PMID- 20147291
TI  - Anti-HIV activity of defective cyanovirin-N mutants is restored by dimerization.
AB  - Cyanovirin-N (CV-N) is a two-domain, cyanobacterial protein that inhibits human
      immunodeficiency virus (HIV) at nanomolar concentrations by binding to high
      mannose sugars on the HIV envelope glycoprotein gp120. The wild type protein can
      exist as a monomer or a domain-swapped dimer with the monomer and dimer
      containing two or four sugar binding sites, respectively, one on each domain.
      Here we demonstrate that monomeric, single binding site mutants are completely
      inactive and that a single site, whether located on domain A or B, is
      insufficient to impart the antiviral activity. Linking inactive, monomeric
      proteins in a head-to-head fashion by an intermolecular disulfide bond or by
      creating an exclusively domain-swapped dimer via a hinge residue deletion
      restored antiviral activity to levels similar to that of wild type CV-N. These
      findings demonstrate unequivocally that multisite binding by CV-N type lectins is
      necessary for viral inhibition.

PMID- 20147292
TI  - Ligand binding and subtype selectivity of the human A(2A) adenosine receptor:
      identification and characterization of essential amino acid residues.
AB  - The crystal structure of the human A(2A) adenosine receptor bound to the A(2A)
      receptor-specific antagonist, ZM241385, was recently determined at 2.6-A
      resolution. Surprisingly, the antagonist binds in an extended conformation,
      perpendicular to the plane of the membrane, and indicates a number of
      interactions unidentified before in ZM241385 recognition. To further understand
      the selectivity of ZM241385 for the human A(2A) adenosine receptor, we examined
      the effect of mutating amino acid residues within the binding cavity likely to
      have key interactions and that have not been previously examined. Mutation of Phe
      168 to Ala abolishes both agonist and antagonist binding as well as receptor
      activity, whereas mutation of this residue to Trp or Tyr had only moderate
      effects. The Met-177 --> Ala mutation impeded antagonist but not agonist binding.
      Finally, the Leu-249 --> Ala mutant showed neither agonist nor antagonist binding
      affinity. From our results and previously published mutagenesis data, we conclude
      that conserved residues Phe-168(5.29), Glu-169(5.30), Asn-253(6.55), and Leu
      249(6.51) play a central role in coordinating the bicyclic core present in both
      agonists and antagonists. By combining the analysis of the mutagenesis data with
      a comparison of the sequences of different adenosine receptor subtypes from
      different species, we predict that the interactions that determine subtype
      selectivity reside in the more divergent "upper" region of the binding cavity
      while the "lower" part of the binding cavity is conserved across adenosine
      receptor subtypes.

PMID- 20147295
TI  - Chemical biology meets biological chemistry minireview series.

PMID- 20147293
TI  - Human ELG1 regulates the level of ubiquitinated proliferating cell nuclear
      antigen (PCNA) through Its interactions with PCNA and USP1.
AB  - The level of monoubiquitinated proliferating cell nuclear antigen (PCNA) is
      closely linked with DNA damage bypass to protect cells from a high level of
      mutagenesis. However, it remains unclear how the level of monoubiquitinated PCNA
      is regulated. Here, we demonstrate that human ELG1 protein, which comprises an
      alternative replication factor C (RFC) complex and plays an important role in
      preserving genomic stability, as an interacting partner for the USP1 (ubiquitin
      specific protease 1)-UAF1 (USP1-associated factor 1) complex, a deubiquitinating
      enzyme complex for PCNA and FANCD2. ELG1 protein interacts with PCNAs that are
      localized at stalled replication forks. ELG1 knockdown specifically resulted in
      an increase in the level of PCNA monoubiquitination without affecting the level
      of FANCD2 ubiquitination. It is a novel function of ELG1 distinct from its role
      as an alternative RFC complex because knockdowns of any other RFC subunits or
      other alternative RFCs did not affect PCNA monoubiquitination. Lastly, we
      identified a highly conserved N-terminal domain in ELG1 that was responsible for
      the USP1-UAF1 interaction as well as the activity to down-regulate PCNA
      monoubiquitination. Taken together, ELG1 specifically directs USP1-UAF1 complex
      for PCNA deubiquitination.

PMID- 20147294
TI  - Structural basis for the growth factor activity of human adenosine deaminase
      ADA2.
AB  - Two distinct adenosine deaminases, ADA1 and ADA2, are found in humans. ADA1 has
      an important role in lymphocyte function and inherited mutations in ADA1 result
      in severe combined immunodeficiency. The recently isolated ADA2 belongs to the
      novel family of adenosine deaminase growth factors (ADGFs), which play an
      important role in tissue development. The crystal structures of ADA2 and ADA2
      bound to a transition state analogue presented here reveal the structural basis
      of the catalytic/signaling activity of ADGF/ADA2 proteins. In addition to the
      catalytic domain, the structures discovered two ADGF/ADA2-specific domains of
      novel folds that mediate the protein dimerization and binding to the cell surface
      receptors. This complex architecture is in sharp contrast with that of monomeric
      single domain ADA1. An extensive glycosylation and the presence of a conserved
      disulfide bond and a signal peptide in ADA2 strongly suggest that ADA2, in
      contrast to ADA1, is specifically designed to act in the extracellular
      environment. The comparison of catalytic sites of ADA2 and ADA1 demonstrates
      large differences in the arrangement of the substrate-binding pockets. These
      structural differences explain the substrate and inhibitor specificity of
      adenosine deaminases and provide the basis for a rational design of ADA2
      targeting drugs to modulate the immune system responses in pathophysiological
      conditions.

PMID- 20147296
TI  - Identification of Conus peptidylprolyl cis-trans isomerases (PPIases) and
      assessment of their role in the oxidative folding of conotoxins.
AB  - Peptidylprolyl cis-trans isomerases (PPIases) are ubiquitous proteins that
      catalyze the cis-trans isomerization of prolines. A number of proteins, such as
      Drosophila rhodopsin and the human immunodeficiency viral protein HIV-1 Gag, have
      been identified as endogenous substrates for PPIases. However, very little is
      known about the interaction of PPIases with small, disulfide-rich peptides.
      Marine cone snails synthesize a wide array of cysteine-rich peptides, called
      conotoxins, many of which contain one or more prolines or hydroxyprolines. To
      identify whether PPIase-associated cis-trans isomerization of these residues
      affects the oxidative folding of conotoxins, we identified, sequenced, and
      expressed three functionally active isoforms of PPIase from the venom gland of
      Conus novaehollandiae, and we characterized their ability to facilitate oxidative
      folding of conotoxins in vitro. Three conotoxins, namely mu-GIIIA, mu-SIIIA, and
      omega-MVIIC, derived from two distinct toxin gene families were assayed. Conus
      PPIase significantly increased the rate of appearance of the native form of mu
      GIIIA, a peptide containing three hydroxyprolines. In contrast, the presence of
      PPIase had no effect on the folding of mu-SIIIA and omega-MVIIC, peptides
      containing no or one proline residue, respectively. We further showed that an
      endoplasmic reticulum-resident PPIase isoform facilitated folding of mu-GIIIA
      more efficiently than two cytosolic isoforms. This is the first study to
      demonstrate PPIase-assisted folding of conotoxins, small disulfide-rich peptides
      with unique structural properties.

PMID- 20147297
TI  - Ubiquitin C-terminal hydrolase-L1 protects cystic fibrosis transmembrane
      conductance regulator from early stages of proteasomal degradation.
AB  - DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) degradation
      involves ubiquitin modification and efficient proteasomal targeting of the
      nascent misfolded protein. We show that a deubiquitinating enzyme, ubiquitin C
      terminal hydrolase-L1 (UCH-L1), is highly expressed in cystic fibrosis (CF)
      airway epithelial cells in vitro and in vivo. We hypothesized that the elevation
      in UCH-L1 in CF cells represents a cellular adaptation to counterbalance
      excessive proteasomal degradation. The bronchial epithelial cell lines IB3-1 (CF,
      high UCH-L1 expression) and S9 (non-CF, low UCH-L1 expression) were transiently
      transfected with wild type (WT) or DeltaF508 CFTR, WT UCH-L1 or small interfering
      RNA-UCH-L1, and a variety of ubiquitin mutants. We observed a positive
      correlation between UCH-L1 expression and steady state levels of WT- or DeltaF508
      CFTR, and this stabilizing effect was confined to the early stages of CFTR
      synthesis. Immunolocalization of UCH-L1 by confocal microscopy revealed a partial
      co-localization with a ribosomal subunit and the endoplasmic reticulum. The UCH
      L1-associated increase in CFTR levels was correlated with an increase in
      ubiquitinated CFTR (CFTR-Ub). Co-transfection with mutant ubiquitins and
      treatment with proteasome inhibitors suggested that UCH-L1 was reducing the
      proteasomal targeting of CFTR during synthesis by shortening conjugated
      polyubiquitin chains. Although not sufficient by itself to rescue mutant CFTR
      therapeutically, the elevation of UCH-L1 and its effect on CFTR processing
      provides insight into its potential roles in CF and other diseases.

PMID- 20147298
TI  - The deubiquitinating enzyme USP17 blocks N-Ras membrane trafficking and
      activation but leaves K-Ras unaffected.
AB  - The proto-oncogenic Ras isoforms (H, N, and K) have a C-terminal CAAX motif and
      undergo the same post-translational processing steps, although they traffic to
      the plasma membrane through different routes. Previously, we have shown that
      overexpression of the deubiquitinating enzyme USP17 inhibits H-Ras localization
      to the plasma membrane. Now we report that whereas H-Ras and N-Ras were unable to
      localize to the plasma membrane in the presence of USP17, K-Ras4b localization
      was unaffected. EGF stimulation was unable to induce N-Ras membrane localization
      in USP17-expressing cells. In addition, N-Ras activity and downstream signaling
      through the MAPK MEK/ERK and PI3K/JNK pathways were blunted. However, we still
      detected abundant N-Ras localization at the ER and Golgi in USP17-expressing
      cells. Collectively, our data showed that the deubiquitinating enzyme USP17
      blocks EGF-induced N-Ras membrane trafficking and activation, but left K-Ras
      unaffected.

PMID- 20147300
TI  - A randomized clinical trial to evaluate ready-made spectacles in an adult
      population in India.
AB  - BACKGROUND: Ready-made spectacles (RMS) have advantages; however, visual
      performance and satisfaction has not been evaluated. METHODS: A 1-month, double
      masked, randomized clinical trial comparing planned continued use and visual
      performance of RMS to Custom Spectacles (CS) in adults aged 18-45 years with > or
      =1 diopter (D) of uncorrected refractive error (URE). RESULTS: A total of 373 of
      400 participants (93%) completed; mean age was 30 +/- 9 years, and 58% were
      female. Average URE was 2.21 +/- 1.31D and habitual vision was 0.58 +/- 0.21
      logMAR (logarithm of Minimum Angle of Resolution, 20/63(+1) Snellen acuity). Ten
      participants with habitual vision better than 20/40 were excluded (3%). A lower
      proportion in the RMS group intended to continue to wear the study spectacles
      after 1 month (165/183, 90% vs 174/180, 97%, P = 0.02). Spectacle vision in the
      eye with lower URE was 0.08 +/- 0.15 vs 0.02 +/- 0.08, P < 0.0001 and higher URE
      was 0.12 +/- 0.18 vs 0.02 +/- 0.08, P < 0.0001 (logMAR) for RMS and CS. Subgroup
      analyses excluding participants with astigmatism > or =2.00 D and anisometropia >
      or =1.00 D (74/363, 20%) found no difference in planned continued use (139/143,
      97% vs 141/146, 97%, P = 1.0) for RMS vs CS. CONCLUSIONS: While vision is
      slightly better with CS, 90% of an adult population with URE planned to continue
      to use their RMS at 1 month. Furthermore, if those without high astigmatism or
      anisometropia are excluded, virtually all are satisfied with RMS and there is no
      difference when compared with CS. The findings of this study support the use of
      RMS for the delivery of refractive services in settings where there is a high
      level of need, limited resources and low access to refractive services.

PMID- 20147301
TI  - The 26S proteasome function and Hsp90 activity involved in the regulation of
      HsfA2 expression in response to oxidative stress.
AB  - Heat shock transcription factor A2 (HsfA2) is induced under environmental stress
      and regulates transcription of various defense-related genes. Thus HsfA2 plays an
      important role in induction of defenses against different types of environmental
      stress, but its mode of regulation remains unknown. To clarify the signal
      transduction pathway involved in the regulation of HsfA2 expression, we
      investigated the effect of MG132, a 26S proteasome inhibitor, or geldanamycin
      (GDA), a heat shock protein 90 (Hsp90) inhibitor, on the transcription of HsfA2
      and its targets, Hsp18.1-CI and ascorbate peroxidase 2 (Apx2), in Arabidopsis T87
      cells. The levels of transcripts were significantly increased by treatment with
      MG132 or GDA. Overexpression of a dexamethazone-inducible dominant-negative form
      of Hsp90.2 in Arabidopsis plants caused significant expression of HsfA2 and its
      target gene on treatment with the compound. Treatment with MG132 or GDA had no
      effect on intracellular levels of reactive oxygen species (ROS). Interestingly,
      the levels of polyubiquitinated proteins as well as the levels of HsfA2
      transcript were rapidly increased under oxidative stress derived from treatment
      with H2O2 or methylviologen, while they were completely suppressed by pre
      treatment with ascorbate, a scavenger of ROS, under oxidative stress. The present
      findings suggest that the inhibition of 26S proteasome function and/or Hsp90
      activity is involved in the induction of HsfA2 expression in response to
      oxidative stress.

PMID- 20147302
TI  - Fast and SNP-tolerant detection of complex variants and splicing in short reads.
AB  - MOTIVATION: Next-generation sequencing captures sequence differences in reads
      relative to a reference genome or transcriptome, including splicing events and
      complex variants involving multiple mismatches and long indels. We present
      computational methods for fast detection of complex variants and splicing in
      short reads, based on a successively constrained search process of merging and
      filtering position lists from a genomic index. Our methods are implemented in
      GSNAP (Genomic Short-read Nucleotide Alignment Program), which can align both
      single- and paired-end reads as short as 14 nt and of arbitrarily long length. It
      can detect short- and long-distance splicing, including interchromosomal
      splicing, in individual reads, using probabilistic models or a database of known
      splice sites. Our program also permits SNP-tolerant alignment to a reference
      space of all possible combinations of major and minor alleles, and can align
      reads from bisulfite-treated DNA for the study of methylation state. RESULTS: In
      comparison testing, GSNAP has speeds comparable to existing programs, especially
      in reads of > or=70 nt and is fastest in detecting complex variants with four or
      more mismatches or insertions of 1-9 nt and deletions of 1-30 nt. Although SNP
      tolerance does not increase alignment yield substantially, it affects alignment
      results in 7-8% of transcriptional reads, typically by revealing alternate
      genomic mappings for a read. Simulations of bisulfite-converted DNA show a
      decrease in identifying genomic positions uniquely in 6% of 36 nt reads and 3% of
      70 nt reads. AVAILABILITY: Source code in C and utility programs in Perl are
      freely available for download as part of the GMAP package at
      http://share.gene.com/gmap.

PMID- 20147303
TI  - SoDA2: a Hidden Markov Model approach for identification of immunoglobulin
      rearrangements.
AB  - MOTIVATION: The inference of pre-mutation immunoglobulin (Ig) rearrangements is
      essential in the study of the antibody repertoires produced in response to
      infection, in B-cell neoplasms and in autoimmune disease. Often, there are
      several rearrangements that are nearly equivalent as candidates for a given Ig
      gene, but have different consequences in an analysis. Our aim in this article is
      to develop a probabilistic model of the rearrangement process and a Bayesian
      method for estimating posterior probabilities for the comparison of multiple
      plausible rearrangements. RESULTS: We have developed SoDA2, which is based on a
      Hidden Markov Model and used to compute the posterior probabilities of candidate
      rearrangements and to find those with the highest values among them. We validated
      the software on a set of simulated data, a set of clonally related sequences, and
      a group of randomly selected Ig heavy chains from Genbank. In most tests, SoDA2
      performed better than other available software for the task. Furthermore, the
      output format has been redesigned, in part, to facilitate comparison of multiple
      solutions. AVAILABILITY: SoDA2 is available online at
      https://hippocrates.duhs.duke.edu/soda. Simulated sequences are available upon
      request.

PMID- 20147304
TI  - A link between H3K27me3 mark and exon length in the gene promoters of pluripotent
      and differentiated cells.
AB  - We conducted a reanalysis of genome-wide histone H3 tail methylation data in
      mammalian pluripotent and differentiated cells. We show that the promoters marked
      with histone H3 lysine 27 trimethylation (H3K27me3) tend to have more exonic
      positions in the promoter regions. However, this is not due to any preferential
      marking on exons over introns by H3K27me3. The relationship is also independent
      the status of histone H3 lysine 4 trimethylation (H3K4me3) mark, CpG content and
      the platforms used in the high-throughput profiling of histone modifications. It
      provides evidence for the link between histone modifications and transcribed
      exons in promoter regions.

PMID- 20147305
TI  - Estimating replicate time shifts using Gaussian process regression.
AB  - MOTIVATION: Time-course gene expression datasets provide important insights into
      dynamic aspects of biological processes, such as circadian rhythms, cell cycle
      and organ development. In a typical microarray time-course experiment,
      measurements are obtained at each time point from multiple replicate samples.
      Accurately recovering the gene expression patterns from experimental observations
      is made challenging by both measurement noise and variation among replicates'
      rates of development. Prior work on this topic has focused on inference of
      expression patterns assuming that the replicate times are synchronized. We
      develop a statistical approach that simultaneously infers both (i) the underlying
      (hidden) expression profile for each gene, as well as (ii) the biological time
      for each individual replicate. Our approach is based on Gaussian process
      regression (GPR) combined with a probabilistic model that accounts for
      uncertainty about the biological development time of each replicate. RESULTS: We
      apply GPR with uncertain measurement times to a microarray dataset of mRNA
      expression for the hair-growth cycle in mouse back skin, predicting both profile
      shapes and biological times for each replicate. The predicted time shifts show
      high consistency with independently obtained morphological estimates of relative
      development. We also show that the method systematically reduces prediction error
      on out-of-sample data, significantly reducing the mean squared error in a cross
      validation study. AVAILABILITY: Matlab code for GPR with uncertain time shifts is
      available at http://sli.ics.uci.edu/Code/GPRTimeshift/ CONTACT:
      ihler@ics.uci.edu.

PMID- 20147306
TI  - Skyline: an open source document editor for creating and analyzing targeted
      proteomics experiments.
AB  - SUMMARY: Skyline is a Windows client application for targeted proteomics method
      creation and quantitative data analysis. It is open source and freely available
      for academic and commercial use. The Skyline user interface simplifies the
      development of mass spectrometer methods and the analysis of data from targeted
      proteomics experiments performed using selected reaction monitoring (SRM).
      Skyline supports using and creating MS/MS spectral libraries from a wide variety
      of sources to choose SRM filters and verify results based on previously observed
      ion trap data. Skyline exports transition lists to and imports the native output
      files from Agilent, Applied Biosystems, Thermo Fisher Scientific and Waters
      triple quadrupole instruments, seamlessly connecting mass spectrometer output
      back to the experimental design document. The fast and compact Skyline file
      format is easily shared, even for experiments requiring many sample injections. A
      rich array of graphs displays results and provides powerful tools for inspecting
      data integrity as data are acquired, helping instrument operators to identify
      problems early. The Skyline dynamic report designer exports tabular data from the
      Skyline document model for in-depth analysis with common statistical tools.
      AVAILABILITY: Single-click, self-updating web installation is available at
      http://proteome.gs.washington.edu/software/skyline. This web site also provides
      access to instructional videos, a support board, an issues list and a link to the
      source code project.

PMID- 20147307
TI  - Assigning roles to DNA regulatory motifs using comparative genomics.
AB  - MOTIVATION: Transcription factors (TFs) are crucial during the lifetime of the
      cell. Their functional roles are defined by the genes they regulate. Uncovering
      these roles not only sheds light on the TF at hand but puts it into the context
      of the complete regulatory network. RESULTS: Here, we present an alignment- and
      threshold-free comparative genomics approach for assigning functional roles to
      DNA regulatory motifs. We incorporate our approach into the Gomo algorithm, a
      computational tool for detecting associations between a user-specified DNA
      regulatory motif [expressed as a position weight matrix (PWM)] and Gene Ontology
      (GO) terms. Incorporating multiple species into the analysis significantly
      improves Gomo's ability to identify GO terms associated with the regulatory
      targets of TFs. Including three comparative species in the process of predicting
      TF roles in Saccharomyces cerevisiae and Homo sapiens increases the number of
      significant predictions by 75 and 200%, respectively. The predicted GO terms are
      also more specific, yielding deeper biological insight into the role of the TF.
      Adjusting motif (binding) affinity scores for individual sequence composition
      proves to be essential for avoiding false positive associations. We describe a
      novel DNA sequence-scoring algorithm that compensates a thermodynamic measure of
      DNA-binding affinity for individual sequence base composition. GOMO's prediction
      accuracy proves to be relatively insensitive to how promoters are defined.
      Because GOMO uses a threshold-free form of gene set analysis, there are no free
      parameters to tune. Biologists can investigate the potential roles of DNA
      regulatory motifs of interest using GOMO via the web (http://meme.nbcr.net).

PMID- 20147308
TI  - Development of the pseudothumb in frogs.
AB  - Frogs have highly conserved hand and foot morphology, possessing four fingers and
      five toes. As an exception, two Japanese ranid frog species, the Otton frog
      Babina subaspera and the dagger frog Babina holsti, possess a unique thumb-like
      structure (the pseudothumb) in the forelimb, giving an appearance of a total of
      five fingers on the hand. To obtain insights into the developmental mechanisms
      that generate this novel character, we investigated the hand morphogenesis of the
      Otton frog. The unique morphological pattern of the pseudothumb was already
      established in juveniles. Surprisingly, the bud-like structure, which is similar
      to the area of inductive activity (e.g. feather buds in birds and the carapacial
      ridge in turtles), was detected over the site where the future prepollex develops
      in larvae. By contrast, this bud-like structure was not found in larvae of other
      ranid species. We discuss possible scenarios that would favour the evolution of
      this very unusual trait in frogs.

PMID- 20147309
TI  - Evolution of virulence when transmission occurs before disease.
AB  - Most models of virulence evolution assume that transmission and virulence are
      constant during an infection. In many viral (HIV and influenza), bacterial (TB)
      and prion (BSE and CWD) systems, disease-induced mortality occurs long after the
      host becomes infectious. Therefore, we constructed a model with two infected
      classes that differ in transmission rate and virulence in order to understand how
      the evolutionarily stable strategy (ESS) depends on the relative difference in
      transmission and virulence between classes, on the transition rate between
      classes and on the recovery rate from the second class. We find that ESS
      virulence decreases when expressed early in the infection or when transmission
      occurs late in an infection. When virulence occurred relatively equally in each
      class and there was disease recovery, ESS virulence increased with increased
      transition rate. In contrast, ESS virulence first increased and then decreased
      with transition rate when there was little virulence early in the infection and a
      rapid recovery rate. This model predicts that ESS virulence is highly dependent
      on the timing of transmission and pathology after infection; thus, pathogen
      evolution may either increase or decrease virulence after emergence in a new
      host.

PMID- 20147310
TI  - Air-breathing adaptation in a marine Devonian lungfish.
AB  - Recent discoveries of tetrapod trackways in 395 Myr old tidal zone deposits of
      Poland (Niedzwiedzki et al. 2010 Nature 463, 43-48 (doi:10.1038/nature.08623))
      indicate that vertebrates had already ventured out of the water and might already
      have developed some air-breathing capacity by the Middle Devonian. Air-breathing
      in lungfishes is not considered to be a shared specialization with tetrapods, but
      evolved independently. Air-breathing in lungfishes has been postulated as
      starting in Middle Devonian times (ca 385 Ma) in freshwater habitats, based on a
      set of skeletal characters involved in air-breathing in extant lungfishes. New
      discoveries described herein of the lungfish Rhinodipterus from marine limestones
      of Australia identifies the node in dipnoan phylogeny where air-breathing begins,
      and confirms that lungfishes living in marine habitats had also developed
      specializations to breathe air by the start of the Late Devonian (ca 375 Ma).
      While invasion of freshwater habitats from the marine realm was previously
      suggested to be the prime cause of aerial respiration developing in lungfishes,
      we believe that global decline in oxygen levels during the Middle Devonian
      combined with higher metabolic costs is a more likely driver of air-breathing
      ability, which developed in both marine and freshwater lungfishes and
      tetrapodomorph fishes such as Gogonasus.

PMID- 20147312
TI  - Utilization of granular solidification during terrestrial locomotion of hatchling
      sea turtles.
AB  - Biological terrestrial locomotion occurs on substrate materials with a range of
      rheological behaviour, which can affect limb-ground interaction, locomotor mode
      and performance. Surfaces like sand, a granular medium, can display solid or
      fluid-like behaviour in response to stress. Based on our previous experiments and
      models of a robot moving on granular media, we hypothesize that solidification
      properties of granular media allow organisms to achieve performance on sand
      comparable to that on hard ground. We test this hypothesis by performing a field
      study examining locomotor performance (average speed) of an animal that can both
      swim aquatically and move on land, the hatchling Loggerhead sea turtle (Caretta
      caretta). Hatchlings were challenged to traverse a trackway with two surface
      treatments: hard ground (sandpaper) and loosely packed sand. On hard ground, the
      claw use enables no-slip locomotion. Comparable performance on sand was achieved
      by creation of a solid region behind the flipper that prevents slipping. Yielding
      forces measured in laboratory drag experiments were sufficient to support the
      inertial forces at each step, consistent with our solidification hypothesis.

PMID- 20147311
TI  - Sperm midpiece length predicts sperm swimming velocity in house mice.
AB  - Evolutionary biologists have argued that there should be a positive relationship
      between sperm size and sperm velocity, and that these traits influence a male's
      sperm competitiveness. However, comparative analyses investigating the
      evolutionary associations between sperm competition risk and sperm morphology
      have reported inconsistent patterns of association, and in vitro sperm
      competition experiments have further confused the issue; in some species, males
      with longer sperm achieve more competitive fertilization, while in other species
      males with shorter sperm have greater sperm competitiveness. Few investigations
      have attempted to address this problem. Here, we investigated the relationship
      between sperm morphology and sperm velocity in house mice (Mus domesticus). We
      conducted in vitro sperm velocity assays on males from established selection
      lines, and found that sperm midpiece size was the only phenotypic predictor of
      sperm swimming velocity.

PMID- 20147313
TI  - Marine no-take zone rapidly benefits endangered penguin.
AB  - No-take zones may protect populations of targeted marine species and restore the
      integrity of marine ecosystems, but it is unclear whether they benefit top
      predators that rely on mobile pelagic fishes. In South Africa, foraging effort of
      breeding African penguins decreased by 30 per cent within three months of closing
      a 20 km zone to the competing purse-seine fisheries around their largest colony.
      After the fishing ban, most of the penguins from this island had shifted their
      feeding effort inside the closed area. Birds breeding at another colony situated
      50 km away, whose fishing grounds remained open to fishing, increased their
      foraging effort during the same period. This demonstrates the immediate benefit
      of a relatively small no-take zone for a marine top predator relying on pelagic
      prey. Selecting such small protected areas may be an important first conservation
      step, minimizing stakeholder conflicts and easing compliance, while ensuring
      benefit for the ecosystems within these habitats.

PMID- 20147314
TI  - Protocols for sampling viral sequences to study epidemic dynamics.
AB  - With more emphasis being put on global infectious disease monitoring, viral
      genetic data are being collected at an astounding rate, both within and without
      the context of a long-term disease surveillance plan. Concurrent with this
      increase have come improvements to the sophisticated and generalized statistical
      techniques used for extracting population-level information from genetic sequence
      data. However, little research has been done on how the collection of these viral
      sequence data can or does affect the efficacy of the phylogenetic algorithms used
      to analyse and interpret them. In this study, we use epidemic simulations to
      consider how the collection of viral sequence data clarifies or distorts the
      picture, provided by the phylogenetic algorithms, of the underlying population
      dynamics of the simulated viral infection over many epidemic cycles. We find that
      sampling protocols purposefully designed to capture sequences at specific points
      in the epidemic cycle, such as is done for seasonal influenza surveillance, lead
      to a significantly better view of the underlying population dynamics than do less
      focused collection protocols. Our results suggest that the temporal distribution
      of samples can have a significant effect on what can be inferred from genetic
      data, and thus highlight the importance of considering this distribution when
      designing or evaluating protocols and analysing the data collected thereunder.

PMID- 20147316
TI  - Transferring vertically aligned carbon nanotubes onto a polymeric substrate using
      a hot embossing technique for microfluidic applications.
AB  - We explored the hot embossing method for transferring vertically aligned carbon
      nanotubes (CNTs) into microfluidic channels, fabricated on poly-methyl
      methacrylate (PMMA). Patterned and unpatterned CNTs were synthesized by microwave
      plasma-enhanced chemical vapour deposition on silicon to work as a stamp. For hot
      embossing, 115 degrees C and 1 kN force for 2 min were found to be the most
      suitable parameters for the complete transfer of aligned CNTs on the PMMA
      microchannel. Raman and SEM studies were used to analyse the microstructure of
      CNTs before and after hot embossing. The PMMA microparticles with dimensions
      (approx. 10 microm in diameter) similar to red blood cells were successfully
      filtered using laminar flow through these microfluidic channels. Finally, a
      microfluidic-based point-of-care device for blood filtration and detection of bio
      molecules is drawn schematically.

PMID- 20147315
TI  - Systems engineering medicine: engineering the inflammation response to infectious
      and traumatic challenges.
AB  - The complexity of the systemic inflammatory response and the lack of a treatment
      breakthrough in the treatment of pathogenic infection demand that advanced tools
      be brought to bear in the treatment of severe sepsis and trauma. Systems
      medicine, the translational science counterpart to basic science's systems
      biology, is the interface at which these tools may be constructed. Rapid initial
      strides in improving sepsis treatment are possible through the use of
      phenomenological modelling and optimization tools for process understanding and
      device design. Higher impact, and more generalizable, treatment designs are based
      on mechanistic understanding developed through the use of physiologically based
      models, characterization of population variability, and the use of control
      theoretic systems engineering concepts. In this review we introduce acute
      inflammation and sepsis as an example of just one area that is currently
      underserved by the systems medicine community, and, therefore, an area in which
      contributions of all types can be made.

PMID- 20147317
TI  - CalDAG-GEFI down-regulation in the striatum as a neuroprotective change in
      Huntington's disease.
AB  - Huntingtin protein (Htt) is ubiquitously expressed, yet Huntington's disease
      (HD), a fatal neurologic disorder produced by expansion of an Htt polyglutamine
      tract, is characterized by neurodegeneration that occurs primarily in the
      striatum and cerebral cortex. Such discrepancies between sites of expression and
      pathology occur in multiple neurodegenerative disorders associated with expanded
      polyglutamine tracts. One possible reason is that disease-modifying factors are
      tissue-specific. Here, we show that the striatum-enriched protein, CalDAG-GEFI,
      is severely down-regulated in the striatum of mouse HD models and is down
      regulated in HD individuals. In the R6/2 transgenic mouse model of HD, striatal
      neurons with the largest aggregates of mutant Htt have the lowest levels of
      CalDAG-GEFI. In a brain-slice explant model of HD, knock-down of CalDAG-GEFI
      expression rescues striatal neurons from pathology induced by transfection of
      polyglutamine-expanded Htt exon 1. These findings suggest that the striking down
      regulation of CalDAG-GEFI in HD could be a protective mechanism that mitigates
      Htt-induced degeneration.

PMID- 20147318
TI  - Genetic variants in ABO blood group region, plasma soluble E-selectin levels and
      risk of type 2 diabetes.
AB  - Blood soluble E-selectin (sE-selectin) levels have been related to various
      conditions such as type 2 diabetes. We performed a genome-wide association study
      among women of European ancestry from the Nurses' Health Study, and identified
      genome-wide significant associations between a cluster of markers at the ABO
      locus (9q34) and plasma sE-selectin concentration. The strongest association was
      with rs651007, which explained approximately 9.71% of the variation in sE
      selectin concentrations. SNP rs651007 was also nominally associated with soluble
      intracellular cell adhesion molecule-1 (sICAM-1) (P = 0.026) and TNF-R2 levels (P
      = 0.018), independent of sE-selectin. In addition, the genetic-inferred ABO blood
      group genotypes were associated with sE-selectin concentrations (P = 3.55 x 10(
      47)). Moreover, we found that the genetic-inferred blood group B was associated
      with a decreased risk (OR = 0.44, 0.27-0.70) of type 2 diabetes compared with
      blood group O, adjusting for sE-selectin, sICAM-1, TNF-R2 and other covariates.
      Our findings indicate that the genetic variants at ABO locus affect plasma sE
      selectin levels and diabetes risk. The genetic associations with diabetes risk
      were independent of sE-selectin levels.

PMID- 20147319
TI  - Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of
      IBMPFD including degeneration in muscle, brain and bone.
AB  - Inclusion body myopathy associated with Paget's disease of bone and
      frontotemporal dementia (IBMPFD) is a dominantly inherited degenerative disorder
      caused by mutations in the valosin-containing protein (VCP) gene. VCP (p97 in
      mouse, TER94 in Drosophila melanogaster and CDC48 in Saccharomyces cerevisiae) is
      a highly conserved AAA(+)-ATPase that regulates a wide array of cellular
      processes. The mechanism of IBMPFD pathogenesis is unknown. Towards elucidating
      the pathogenic mechanism we have developed and characterized transgenic mice with
      ubiquitous expression of wild-type and disease-causing versions of human VCP/p97.
      Here, we report that mice expressing VCP/p97 harboring the mutations R155H or
      A232E develop pathology that is limited to muscle, brain and bone, recapitulating
      the spectrum of disease in humans with IBMPFD. The mice exhibit progressive
      muscle weakness and pathological examination of muscle shows classic
      characteristics of inclusion body myopathy including rimmed vacuoles and TDP-43
      pathology. The mice exhibit abnormalities in behavioral testing and pathological
      examination of the brain shows widespread TDP-43 pathology. Furthermore,
      radiological examination of the skeleton reveals that mutant mice develop severe
      osteopenia accompanied by focal lytic and sclerotic lesions in vertebrae and
      femur. In vitro studies indicate that mutant VCP causes inappropriate activation
      of the NF-kappaB signaling cascade, which could contribute to the mechanism of
      pathogenesis in multiple tissues including muscle, bone and brain.

PMID- 20147321
TI  - Dok-7 promotes slow muscle integrity as well as neuromuscular junction formation
      in a zebrafish model of congenital myasthenic syndromes.
AB  - The small signalling adaptor protein Dok-7 has recently been reported as an
      essential protein of the neuromuscular junction (NMJ). Mutations resulting in
      partial loss of Dok-7 activity cause a distinct limb-girdle subtype of the
      inherited NMJ disorder congenital myasthenic syndromes (CMSs), whereas complete
      loss of Dok-7 results in a lethal phenotype in both mice and humans. Here we
      describe the zebrafish orthologue of Dok-7 and study its in vivo function. Dok-7
      deficiency leads to motility defects in zebrafish embryos and larvae. The
      relative importance of Dok-7 at different stages of NMJ development varies; it is
      crucial for the earliest step, the formation of acetylcholine receptor (AChR)
      clusters in the middle of the muscle fibre prior to motor neuron contact. At
      later stages, presence of Dok-7 is not absolutely essential, as focal and non
      focal synapses do form when Dok-7 expression is downregulated. These contacts
      however are smaller than in the wild-type zebrafish, reminiscent of the
      neuromuscular endplate pathology seen in patients with DOK7 mutations.
      Intriguingly, we also observed changes in slow muscle fibre arrangement;
      previously, Dok-7 has not been linked to functions other than postsynaptic AChR
      clustering. Our results suggest an additional role of Dok-7 in muscle. This role
      seems to be independent of the muscle-specific tyrosine kinase MuSK, the known
      binding partner of Dok-7 at the NMJ. Our findings in the zebrafish model
      contribute to a better understanding of the signalling pathways at the NMJ and
      the pathomechanisms of DOK7 CMSs.

PMID- 20147320
TI  - Discrete subcellular partitioning of human retrotransposon RNAs despite a common
      mechanism of genome insertion.
AB  - Despite the immense significance retrotransposons have had for genome evolution
      much about their biology is unknown, including the processes of forming their
      ribonucleoprotein (RNP) particles and transporting them about the cell.
      Suppression of retrotransposon expression, together with the presence of
      retrotransposon sequence within numerous mRNAs, makes tracking endogenous L1 RNP
      particles in cells problematic. We overcame these difficulties by assaying in
      living and fixed cells tagged-RNPs generated from constructs expressing
      retrotransposition-competent L1s. In this way, we demonstrate for the first time
      the subcellular colocalization of L1 RNA and proteins ORF1p and ORF2p, and show
      their targeting together to cytoplasmic foci. Foci are often associated with
      markers of cytoplasmic stress granules. Furthermore, mutation analyses reveal
      that ORF1p can direct L1 RNP distribution within the cell. We also assayed RNA
      localization of the non-autonomous retrotransposons Alu and SVA. Despite a
      requirement for the L1 integration machinery, each manifests unique features of
      subcellular RNA distribution. In nuclei Alu RNA forms small round foci partially
      associated with marker proteins for coiled bodies, suborganelles involved in the
      processing of non-coding RNAs. SVA RNA patterning is distinctive, being
      cytoplasmic but without prominent foci and concentrated in large nuclear
      aggregates that often ring nucleoli. Such variability predicts significant
      differences in the life cycles of these elements.

PMID- 20147322
TI  - Squalamine, an original chemosensitizer to combat antibiotic-resistant gram
      negative bacteria.

PMID- 20147323
TI  - Risk factors and prognosis of post-operative pneumonia due to Pseudomonas
      aeruginosa following cardiac surgery.

PMID- 20147324
TI  - Clinical mid-term results after tricuspid valve replacement.
AB  - Tricuspid valve replacement (TVR) is associated with high mortality and
      morbidity. Frequently, TVR is performed in critically ill patients with high
      frequency of re-intervention. We analyzed our experience in TVR focusing on
      predicting risk factors, mid-term survival and quality of life assessed with a
      Short-Form 36 Health Survey (SF-36) questionnaire. Between January 1992 and May
      2007, 81 consecutive patients underwent TVR (54 re-interventions, 66.7%; 46
      procedures, associated with a left-sided operation, 56.8%). There were 59 females
      (73%) with a mean age of 59.3+/-11.6 years. The most prevalent etiology was
      rheumatic fever (61.7%). Pulmonary hypertension was present in 64%. Mean left
      ventricle ejection fraction (LVEF) was 56.6% and mean right ventricle ejection
      fraction (RVEF) was 48.1%. All but four patients (4.9%) received a bio
      prosthesis. Hospital mortality was 9.88%. The mean follow-up was 61+/-42 months.
      Survival was 68% at five years. Univariate predictors of hospital mortality were
      atrial fibrillation (AFib) (P<0.01), associated procedures on the left heart
      (P=0.025) and preoperative chronic right heart failure symptoms (P<0.01). At
      follow-up: 10.8% of patients had a pace-maker (PM) induced rhythm; the mean SF-36
      score was 51.1+/-4.8 (range 59-38). Age (P=0.015), associated procedures
      (P=0.024) and previous cardiovascular surgery (P=0.015) were univariate
      predictors of the SF-36 score. At a multivariate analysis LVEF, venous congestion
      and pulmonary artery pressures (PAPs) were related with a SF-36 score.

PMID- 20147326
TI  - Experimental cooling during incubation leads to reduced innate immunity and body
      condition in nestling tree swallows.
AB  - Nest microclimate can have strong effects that can carry over to later life
      history stages. We experimentally cooled the nests of tree swallows (Tachycineta
      bicolor). Females incubating in cooled nests reduced incubation time and allowed
      egg temperatures to drop, leading to extended incubation periods. We partially
      cross-fostered nestlings to test carry-over effects of cooling during incubation
      on nestling innate constitutive immunity, assessed through bacteria killing
      ability (BKA) of blood. Nestlings that had been cooled as eggs showed a lower
      ability to kill bacteria than control nestlings, regardless of the treatment of
      their foster mother. However, there was no effect of treatment of rearing females
      on nestling BKA in control nestlings, even though cooled females made
      significantly fewer feeding visits than did control females. This suggests that
      the effect of cooling occurred during incubation and was not due to carry-over
      effects on nestling condition. Nestlings that were exposed to experimental
      cooling as embryos had lower residual body mass and absolute body mass at all
      four ages measured. Our results indicate that environmental conditions and trade
      offs experienced during one stage of development can have important carry-over
      effects on later life-history stages.

PMID- 20147325
TI  - Colour appearance and compensation in the near periphery.
AB  - The spectral sensitivity of the visual system varies markedly between the fovea
      and surrounding periphery owing in part to the rapid fall in macular pigment
      density with eccentricity. We examined how colour appearance changes between the
      fovea and near periphery (8 degrees) by measuring achromatic loci and the loci of
      unique and binary hues. Chosen colours remained much more similar at the two
      locations than predicted by the change in spectral sensitivity. Compensation for
      white may reflect long-term gain changes within the cones that equate sensitivity
      for the local average stimulus in the fovea and periphery. However, adjusting
      only to the average stimulus cannot correct for all of the effects of a spectral
      sensitivity change, and predicts differences in colour percepts between the fovea
      and periphery that were not observed. The similarities in hue percepts at 0 and 8
      degrees thus suggest that additional processes help compensate colour appearance
      to maintain constancy in the near periphery. We model the results of previous
      studies to show that similar adjustments are implied by age-related changes in
      lens pigment, and to show that these adjustments are consistent with previous
      measurements of peripheral colour appearance based on hue cancellation.

PMID- 20147327
TI  - Visual pigment in the lens eyes of the box jellyfish Chiropsella bronzie.
AB  - Box jellyfish (Cubomedusae) possess a unique visual system comprising 24 eyes of
      four morphological types. Moreover, box jellyfish display several visually guided
      behaviours, including obstacle avoidance and light-shaft attractance. It is
      largely unknown what kind of visual information box jellyfish use for carrying
      out these behaviours. Brightness contrast is almost certainly involved, but it is
      also possible that box jellyfish extract colour information from their
      surroundings. The possible presence of colour vision in box jellyfish has
      previously been investigated using behavioural, electrophysiological and
      immunohistochemical methods. However, the results from these studies are to some
      degree conflicting and inconclusive. Here, we present results from an
      investigation into the visual system of the box jellyfish Chiropsella bronzie,
      using microspectrophotometry and immunohistochemistry. Our results strongly
      indicate that only one type of visual pigment is present in the upper and lower
      lens eyes with a peak absorbance of approximately 510 nm. Additionally, the
      visual pigment appears to undergo bleaching, similar to that of vertebrate visual
      pigments.

PMID- 20147328
TI  - Heterogeneity in chronic myeloid leukaemia dynamics during imatinib treatment:
      role of immune responses.
AB  - Previous studies have shown that during imatinib therapy, the decline of chronic
      myeloid leukaemia BCR-ABL transcript numbers involves a fast phase followed by a
      slow phase in averaged datasets. Drug resistance leads to regrowth. In this
      paper, variation of treatment responses between patients is examined. A
      significant positive correlation is found between slopes of the fast and the slow
      phase of decline. A significant negative correlation is found between slopes of
      the slow phase of decline and the regrowth phase. No correlation is found between
      slopes of the fast phase of decline and the regrowth phase. A mathematical model
      that is successfully fitted to diverse clinical profiles explains these
      correlations by invoking the immune response as a key determinant of tumour
      decline during treatment. Boosting immunity during drug therapy could enhance the
      response to treatment in patients.

PMID- 20147329
TI  - The fine structure of honeybee head and body yaw movements in a homing task.
AB  - Honeybees turn their thorax and thus their flight motor to change direction or to
      fly sideways. If the bee's head were fixed to its thorax, such movements would
      have great impact on vision. Head movements independent of thorax orientation can
      stabilize gaze and thus play an important and active role in shaping the
      structure of the visual input the animal receives. Here, we investigate how gaze
      and flight control interact in a homing task. We use high-speed video equipment
      to record the head and body movements of honeybees approaching and departing from
      a food source that was located between three landmarks in an indoor flight arena.
      During these flights, the bees' trajectories consist of straight flight segments
      combined with rapid turns. These short and fast yaw turns ('saccades') are in
      most cases accompanied by even faster head yaw turns that start about 8 ms
      earlier than the body saccades. Between saccades, gaze stabilization leads to a
      behavioural elimination of rotational components from the optical flow pattern,
      which facilitates depth perception from motion parallax.

PMID- 20147330
TI  - Species interactions-area relationships: biological invasions and network
      structure in relation to island area.
AB  - The relationship between species number and island area is a fundamental rule in
      ecology. However, the extent to which interactions with exotic species and how
      the structure of species interactions is related to island area remain
      unexplored. Here, I document the relationship between island area and (i)
      interactions with exotic species and (ii) network structure of species
      interactions in the context of mutualistic interactions between ants and
      extrafloral nectary-bearing plants on the oceanic Ogasawara (Bonin) Islands,
      Japan. Pooled data contained 122 interactions among 19 plant (including five
      exotic) and 23 ant (including 20 exotic) species. Of the observed interactions,
      82.8 per cent involved at least one exotic species, ranging from 68.2 to 86.4 per
      cent among islands. The number of links including exotic species increased in
      proportion to island area, although the number of links excluding exotic species
      did not. These results indicate that the number of interactions with exotic
      species increased in proportion to island area. Connectance, or the proportion of
      interactions actually observed among all possible interactions, decreased with
      island area. Nestedness, an asymmetry index in the species interaction network,
      also decreased with island area. Therefore, island area affects both the number
      of interactions with exotic species and the network structure.

PMID- 20147331
TI  - Nectar yeasts warm the flowers of a winter-blooming plant.
AB  - Yeasts are ubiquitous in terrestrial and aquatic microbiota, yet their ecological
      functionality remains relatively unexplored in comparison with other micro
      organisms. This paper formulates and tests the novel hypothesis that heat
      produced by the sugar catabolism of yeast populations inhabiting floral nectar
      can increase the temperature of floral nectar and, more generally, modify the
      within-flower thermal microenvironment. Two field experiments were designed to
      test this hypothesis for the winter-blooming herb Helleborus foetidus
      (Ranunculaceae). In experiment 1, the effect of yeasts on the within-flower
      thermal environment was tested by excluding them from flowers, while in
      experiment 2 the test involved artificial inoculation of virgin flowers with
      yeasts. Nectary temperature (T(nect)), within-flower air temperature (T(flow))
      and external air temperature (T(air)) were measured on experimental and control
      flowers in both experiments. Experimental exclusion of yeasts from the nectaries
      significantly reduced, and experimental addition of yeasts significantly
      increased, the temperature excess of nectaries (DeltaT(nect) = T(nect) - T(air))
      and the air space inside flowers in relation to the air just outside the flowers.
      In non-experimental flowers exposed to natural pollinator visitation,
      DeltaT(nect) was linearly related to log yeast cell density in nectar, and
      reached +6 degrees C in nectaries with the densest yeast populations. The warming
      effect of nectar-dwelling yeasts documented in this study suggests novel
      ecological mechanisms potentially linking nectarivorous microbes with winter
      blooming plants and their insect pollinators.

PMID- 20147332
TI  - Productivity responses of a widespread marine piscivore, Gadus morhua, to oceanic
      thermal extremes and trends.
AB  - Climate change will have major consequences for population dynamics and life
      histories of marine biota as it progresses in the twenty-first century. These
      impacts will differ in magnitude and direction for populations within individual
      marine species whose geographical ranges span large gradients in latitude and
      temperature. Here we use meta-analytical methods to investigate how recruitment
      (i.e. the number of new fish produced by spawners in a given year which
      subsequently grow and survive to become vulnerable to fishing gear) has reacted
      to temperature fluctuations, and in particular to extremes of temperature, in cod
      populations throughout the north Atlantic. Temperature has geographically
      explicit effects on cod recruitment. Impacts differ depending on whether
      populations are located in the upper (negative effects) or in the lower (positive
      effects) thermal range. The probabilities of successful year-classes in
      populations living in warm areas is on average 34 per cent higher in cold
      compared with warm seasons, whereas opposite patterns exist for populations
      living in cold areas. These results have implications for cod dynamics,
      distributions and phenologies under the influence of ocean warming, particularly
      related to not only changes in the mean temperature, but also its variability
      (e.g. frequency of exceptionally cold or warm seasons).

PMID- 20147334
TI  - Gemcitabine-based cytotoxic doublets chemotherapy for advanced pancreatic cancer:
      updated subgroup meta-analyses of overall survival.
AB  - OBJECTIVE: Previous meta-analyses showed a survival advantage with gemcitabine
      (GEM)-based combinations over GEM in advanced pancreatic cancer. Therefore, it
      would be valuable to explore the specific active regimens based on a subgroup
      meta-analysis. METHODS: Updated data by comprehensive search of the literature
      from databases and conference proceedings. Subgroup meta-analysis compared GEM
      with GEM-based doublets chemotherapy in terms of 6-month overall survival (OS)
      and 1-year OS. RESULTS: Eighteen randomized controlled trials with 4237 patients
      were included, which were divided into five subgroups: GEM/capecitabine,
      GEM/cisplatin, GEM/5-fluorouracil, GEM/irinotecan and GEM/oxaliplatin. In each
      subgroup, risk ratios (RRs) for 6-month OS were 0.85 (P = 0.04), 0.99 (P = 0.88),
      0.95 (P = 0.46), 1.03 (P = 0.77) and 0.80 (P = 0.001), respectively, and RRs for
      1-year OS were 0.94 (P = 0.14), 0.99 (P = 0.75), 0.96 (P = 0.19), 1.00 (P = 0.97)
      and 0.93 (P = 0.05), respectively. A meta-analysis of the trials with adequate
      information on performance status (PS) was performed in four trials with 1325
      patients. Patients with a good PS did not show a survival benefit when receiving
      combination chemotherapy. RRs for 6-month and 1-year OS were 0.82 (P = 0.18) and
      0.93 (P = 0.08). In contrast, application of combination chemotherapy to patients
      with a poor PS appeared to be harmful. RRs were 1.17 (P = 0.04) for 6-month OS
      and 1.09 (P = 0.04) for 1-year OS. CONCLUSIONS: The meta-analysis indicated a
      significant survival benefit when GEM was either combined with capcitabine or
      oxaliplatin. On the basis of a preliminary subgroup analysis, pancreatic cancer
      patients with a poor PS appeared to have a worse survival benefit from GEM-based
      cytotoxic doublets.

PMID- 20147333
TI  - Adverse events experienced by homecare patients: a scoping review of the
      literature.
AB  - PURPOSE: The paper summarizes the results of a scoping review that focused on the
      occurrence of adverse events experienced by homecare patients. DATA SOURCES: The
      literature search covered published and grey literature between 1998 and 2007.
      Databases searched included: MEDLINE, EMBASE, CINAHL and EBM REVIEWS including
      the Cochrane Library, AGELINE, the National Patient Safety Foundation
      Bibliography, Agency for Healthcare Research and Quality and the Patient Safety
      Net bibliography. STUDY SELECTION: Papers included research studies, review
      articles, policy papers, opinion articles and legal briefs. Inclusion criteria
      were: (i) homecare directed services provided in the home by healthcare
      professionals or caregivers; (ii) addressed a characteristic relevant to patient
      experienced adverse events (e.g. occurrences, rates, definitions, prevention or
      outcomes); and (iii) were in English. Data extraction A pool of 1007 articles was
      reduced to 168 after analysis. Data were charted according to six categories:
      definitions, rates, causes, consequences, interventions and policy. RESULTS:
      Eight categories emerged: adverse drug events, line-related, technology-related,
      infections and urinary catheters, wounds, falls, studies reporting multiple rates
      and other. Reported overall rates of adverse events ranged from 3.5 to 15.1% with
      higher rates for specific types. Few intervention studies were found. Adverse
      events were commonly associated with communication problems. Policy suggestions
      included the need to improve assessments, monitoring, education, coordination and
      communication. CONCLUSION: A standardized definition of adverse events in the
      homecare setting is needed. Prospective cohort studies are needed to improve
      estimates and intervention studies should be undertaken to reduce the risk that
      homecare patients will experience adverse events.

PMID- 20147335
TI  - Gene expression profiles of single human mature oocytes in relation to age.
AB  - BACKGROUND: The development competence of human oocytes declines with increasing
      age. The objective of this study was to investigate the effect of age on gene
      expression profile in mature human oocytes. METHODS: mRNA was isolated for whole
      genome gene expression microarray analysis from metaphase II (MII) oocytes
      donated by IVF or ICSI patients [10 women aged <36 years (younger) and five women
      aged 37-39 years (both inclusive) (older)] undergoing controlled ovarian
      stimulation. The oocytes were donated and prepared immediately after recovery
      from the follicle. RT-PCR on additional four younger and two older oocytes
      confirmed the array analysis. RESULTS: On the basis of 15 independent replicates
      of single MII oocytes, 7470 genes (10 428 transcripts) were identified as present
      in the MII oocytes. Of these, 342 genes showed a significantly different
      expression level between the two age groups; notably, genes annotated to be
      involved in cell cycle regulation, chromosome alignment (e.g. MAD2L1 binding
      protein), sister chromatid separation (e.g. separase), oxidative stress and
      ubiquitination. The top signaling network affected by age was 'cell cycle and
      organism development' (e.g. SMAD2 and activin B1 receptor). CONCLUSION: There is
      a substantial difference between younger and older oocytes in the transcriptional
      level of genes involved in central biological functions of the oocytes, thus
      providing information on processes that may be associated with the ageing
      phenomenon and possibly contributing to decreased fertility.

PMID- 20147336
TI  - Association between phthalate exposure and glutathione S-transferase M1
      polymorphism in adenomyosis, leiomyoma and endometriosis.
AB  - BACKGROUND: Phthalates are known to have estrogenic effects in cell models and
      experimental animals. However, the evidence regarding the effects of phthalates
      on human reproduction is still limited. We conducted a case-control study to
      determine whether estrogen-dependent diseases are associated with phthalate
      exposure and how the glutathione S-transferase M1 (GSTM1; a major detoxification
      enzyme) genotype modulates the risk. METHODS: We recruited subjects who underwent
      laparotomy and had pathologic confirmation of endometriosis (EN) (n = 28),
      adenomyosis (AD) (n = 16) and leiomyoma (LEI) (n = 36) from the Department of
      Obstetrics and Gynecology at a medical center in Taiwan between 2005 and 2007.
      Controls (n = 29) were patients without any of the three aforementioned
      gynecologic conditions. Urine samples were collected before surgery and analyzed
      for seven phthalate metabolites using liquid chromatography-tandem mass
      spectrometry. Peripheral lymphocytes were used for GSTM1 genotype determination.
      RESULTS: Patients with LEIs had significantly higher levels of total urinary mono
      ethylhexyl phthalate (SigmaMEHP; 52.1 versus 18.9 microg/g creatinine, P < 0.05)
      than the controls, whereas patients with EN had an increased level of urinary
      mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine, P < 0.05). Subjects
      with GSTM1 null genotype had significantly increased odds for AD relative to
      those with GSTM1 wild genotype [odds ratio (OR) = 5.30; 95% CI, 1.22-23.1], even
      after adjustment for age and phthalate exposure. Subjects who carried the GSTM1
      null genotype and had a high urinary level of SigmaMEHP showed a significantly
      increased risk for AD (OR = 10.4; 95% CI, 1.26-85.0) and LEIs (OR = 5.93; 95% CI,
      1.10-31.9) after adjustment for age, compared with those with GSTM1 wild-type and
      low urinary level of SigmaMEHP. CONCLUSIONS: These results suggest that both
      GSTM1 null and phthalate exposure are associated with AD and LEI. Larger studies
      are warranted to investigate potential interaction between GSTM1 null and
      phthalate exposure in the etiology of estrogen-dependent gynecologic conditions.

PMID- 20147337
TI  - Separating the effects of tree size and meristem maturation on shoot development
      of grafted scions of red spruce (Picea rubens Sarg.).
AB  - In order to separate the effects of size and meristem maturation on age-related
      changes in shoot growth behaviour, a reciprocal grafting experiment was conducted
      involving juvenile (J), mid-age (MA) and old-growth (OG) red spruce (Picea rubens
      Sarg.) trees as both scion donors and rootstock. The effects of rootstock and
      scion age on vegetative growth, foliar morphology and reproductive development
      were assessed over 7 years after grafting. Vegetative growth potential declines
      with meristem maturation, but the high growth potential of J meristems on J
      rootstock cannot be expressed when J scions are grafted on MA and OG rootstock.
      Branch density decreases with meristem maturation. The tendency for high J branch
      density is expressed across all rootstock ages, but is minimally expressed on MA
      rootstock where elongation of terminal shoots is significantly greater than on OG
      rootstock. Both needle width and leaf mass area increase with meristem maturation
      and increasing tree size. Reproductive competence is mainly a function of
      meristem maturity, and rootstock had little effect on strobilus development,
      although the more fecund rootstocks did promote some flowering on J scions.
      Developmental decline in height growth does not appear to be a function of
      decreased meristem vigour, but reduced terminal long shoot elongation and
      decreased apical control in OG trees will reduce height growth.

PMID- 20147338
TI  - Metabolic profiling in colorectal cancer reveals signature metabolic shifts
      during tumorigenesis.
AB  - Colorectal cancer (CRC) arises as the consequence of progressive changes from
      normal epithelial cells through polyp to tumor, and thus is an useful model for
      studying metabolic shift. In the present study, we studied the metabolomic
      profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS)
      and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems
      level view of the shift in metabolism in cells progressing along the path to CRC.
      Colonic tissues including tumor, polyps and adjacent matched normal mucosa from
      26 patients with sporadic CRC from freshly isolated resections were used for this
      study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data
      suggest there was a distinct profile change of a wide range of metabolites from
      mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors
      were elevated, suggesting higher energy needs for increased cellular
      proliferation. In contrast, significant depletion of glucose and inositol in
      polyps revealed that glycolysis may be critical in early tumorigenesis. In
      addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric
      acid concentration, suggest that the purine biosynthesis pathway could have been
      substituted by the salvage pathway in CRC. Further, there was a step-wise
      reduction of deoxycholic acid concentration from mucosa to tumors. It appears
      that to gain a growth advantage, cancer cells may adopt alternate metabolic
      pathways in tumorigenesis and this flexibility allows them to adapt and thrive in
      harsh environment.

PMID- 20147339
TI  - The effects of intra-cage aspen tube on cardiac morphology and gene expression.
AB  - According to the European recommendations rodents should be provided with a nest
      box if there is insufficient nesting material to build a complete, covered nest.
      Rats are generally poor nest builders; hence an additional structure is needed.
      Optimally, housing refinement may be combined with better science; at least it
      should not detract from the scientific integrity. In order to evaluate these
      options, there is a need to assess the items used in individual research
      projects. Studies investigating molecular mechanisms of cardiac hypertrophy and
      heart failure are typically long-lasting studies; therefore, refinement of the
      housing of rats in these studies is important. The aim of this study was to
      evaluate in rats whether a wooden tube has any impact on cardiac morphology or on
      basal gene expression of atrial natriuretic peptide (ANP) and brain natriuretic
      peptide (BNP); known markers of cardiac overload, hypertrophy and heart failure.
      The experimental protocol simulated cardiovascular studies, but without any
      surgical operations. A total of 42 male Hsd:SD rats were used in an eight-week
      experiment. After weaning, the experimental group was provided with a rectangular
      aspen tube and nesting material, and the control group with only nesting
      material. ANP and BNP gene expression were measured from the left ventricles with
      Northern blot analysis postmortem along with the absolute weights of the whole
      heart, left and right atria and left and right chambers. The weights of the whole
      heart and left chamber were also analysed in relation to body weight. No
      statistically significant differences were observed in any of these variables.
      The inter-individual variation was also unchanged by the cage item. In
      conclusion, the aspen tube does not disrupt research results or alter the number
      of animals needed and can therefore be recommended for enrichment purposes in
      cardiovascular studies.

PMID- 20147340
TI  - Never wrestle with a pig ...

PMID- 20147343
TI  - Coinheritance of severe von Willebrand disease with Glanzmann thrombasthenia.
AB  - A 35-years old male patient presented severe bleeding was diagnosed to have type
      3 von Willebrand disease (VWD) and carrier for Glanzmann thrombasthenia (GT).
      Propositus and family members were studied through basic coagulation tests and
      genomic DNA analysis. Two offspring of the family were diagnosed to have GT
      through platelet aggregation along with VWD carrier. The patient with VWD was
      found positive for homozygous truncating mutation R1659X in VWF gene, and all
      offspring were heterozygous carriers of null allele. Hence, propositus was a
      carrier of GT with severe type 3 VWD and wife was a carrier of GT. Thus, it is
      concluded that there is importance of careful studies of patients even from
      nonconsanguineous families to exclude unusual coinheritance of congenital
      hemostatic disorders. If single replacement therapy in patient not responding
      well then probably co-expression of coagulopathies required and multiple
      replacement therapy should be given according to clinical and laboratory
      features.

PMID- 20147344
TI  - Evaluation of the siblings of physically abused children: a comparison of child
      protective services caseworkers and child abuse physicians.
AB  - Current theories suggest that all children in a home are at risk for physical
      abuse, when one child is abused. However, little evidence exists to guide
      decisions regarding the medical management of siblings of physically abused
      children (contact children [CC]). This study sought to compare child protective
      services (CPS) caseworkers' and child abuse physicians' (CAP) recommendations
      regarding the need for medical evaluation of CC in case scenarios of unequivocal
      physical abuse. In all cases, caseworkers and physicians disagreed on which CC
      warranted a medical evaluation. In addition, 25% of caseworkers did not think
      that physicians should make recommendations on the need for medical evaluation of
      CC. The findings of the authors suggest that the home visit is a critical part of
      the decision-making process for caseworkers and that it often acts as a
      substitute for a medical evaluation. Caseworkers indicated that visible injury to
      the contact child and severity of injury to the index child were among the most
      important factors in deciding which CC need a medical evaluation. Although
      caseworkers and physicians disagree on certain issues related to the evaluation
      of CC, it is clear that limited resources should be directed at CC at highest
      risk for physical abuse.

PMID- 20147341
TI  - Dietary soy may not confound acute experimental stroke infarct volume outcomes in
      ovariectomized female rats.
AB  - Oestrogen administration can alter experimental stroke outcomes. Soy as a source
      of phytoestrogens may therefore modulate responses in 'oestrogen-sensitive'
      stroke models, thus potentially confounding results. We evaluated the effects of
      dietary soy on acute infarct volumes in a pilot study using a rat focal stroke
      model. We hypothesized that ovariectomized (OVX) rats fed a soy-rich diet would
      have smaller acute infarct volumes than rats fed a soy-free diet. OVX rats were
      randomly assigned to a soy-free (n = 6) or a soy-rich (n = 6) diet for four weeks
      and weighed weekly. Following the dietary trial, rats underwent 2 h of middle
      cerebral artery occlusion (MCAO). Mean arterial blood pressure, rectal and
      temporalis muscle temperatures, arterial blood gases and blood glucose were
      recorded peri-ischaemia. Rats were euthanized 22 h following 2 h of MCAO. Brains
      were stained with 2,3,5-triphenyl tetrazolium chloride for acute infarct volume
      analysis. Uterine weight and histology were also evaluated as additional internal
      oestrogen-sensitive controls. Rats on the soy-free diet had greater gains in body
      weight (259 +/- 6% baseline body weight) than rats on the soy-rich diet (238 +/-
      4% baseline body weight). No differences were seen in uterine weight and
      histology, peri-ischaemic physiological parameters and infarct volumes between
      the treatment groups. The results of this pilot study suggest that the dietary
      soy level tested may not alter acute infarct volumes in ischaemic female rat
      brain. More studies addressing the potential confounding effects of dietary soy
      in 'oestrogen-sensitive' stroke models are needed if investigators are to make
      informed choices regarding diets used in experimental stroke research.

PMID- 20147345
TI  - Epidemiological data and comorbidities of 428 patients hospitalized with
      erysipelas.
AB  - The aim of this study was to evaluate the epidemiological data and the main
      comorbidities of patients with erysipelas admitted to a tertiary hospital. All
      patients admitted due to erysipelas during the period from 1999 to 2008 were
      included in a prospective and cross-sectional study. The Fisher exact test and
      logistic regression were used for statistical analysis. A total of 428
      individuals were hospitalized with 41 rehospitalizations; 51.17% of the patients
      were women, the mean age was 58.6 years. The main comorbidities were hypertension
      (51.6%), diabetes mellitus (41.6%), chronic venous insufficiency (36.2%), other
      cardiovascular diseases (33.2%) including angina, peripheral arterial
      insufficiency, acute myocardial infarction, and strokes, obesity (12.1%), chronic
      renal failure (6.8%), neoplasms (4.9%), cirrhosis (4.9%), chronic lymphedema
      (4.2%), and leg ulcers (2.6%). Erysipelas is a seasonal disease that affects
      adults and the elderly people, has a repetitive nature, and is associated with
      comorbidities.

PMID- 20147346
TI  - The influence of preoperative use of ventricular assist devices on survival after
      heart transplantation: propensity score matched analysis.
AB  - OBJECTIVE: To determine the influence of the preoperative placement of a left
      ventricular assist device on survival after heart transplantation. DESIGN:
      Prospective cohort study. SETTING: Organ sharing database with patient level data
      on heart transplants in the United States. PARTICIPANTS: 2786 adults aged 18 or
      older in status 1A or 1B (highest priority for heart transplantation with either
      some form of ventricular assist device, intravenous inotrope, or life expectancy
      of less than seven days), based on the United Network for Organ Sharing Registry,
      1996-2004. MAIN OUTCOME MEASURE: Survival after heart transplantation in patients
      who did and did not receive a left ventricular assist device. RESULTS: The left
      ventricular assist device was not associated with decreased survival, even after
      the data were stratified by propensity score (the odds of being a treated
      patient). Inspection of the strata showed no difference in survival between
      patients who received the device and those who did not. The hazard ratios in
      strata 1 to 5 were 0.69, 1.37, 1.55, 0.75, and 1.19, respectively, and none was
      statistically significant. CONCLUSION: Overall, survival after heart
      transplantation in patients who received a left ventricular assist device before
      transplantation was comparable to those who did not receive the device.

PMID- 20147358
TI  - Bucking the inequality gradient through early child development.

PMID- 20147357
TI  - Maintaining the male germline: regulation of spermatogonial stem cells.
AB  - Spermatogonial stem cells (SSCs) are a self-renewing population of adult stem
      cells capable of producing progeny cells for sperm production throughout the life
      of the male. Regulation of the SSC population includes establishment and
      maintenance of a niche microenvironment in the seminiferous tubules of the
      testis. Signaling from somatic cells within the niche determines the fate of SSCs
      by either supporting self-renewal or initiating differentiation leading to
      meiotic entry and production of spermatozoa. Despite the importance of these
      processes, little is known about the biochemical and cellular mechanisms that
      govern SSC fate and identity. This review discusses research findings regarding
      systemic, endocrine, and local cues that stimulate somatic niche cells to produce
      factors that contribute to the homeostasis of SSCs in mammals. In addition to
      their importance for male fertility, SSCs represent a model for the investigation
      of adult stem cells because they can be maintained in culture, and the presence,
      proliferation, or loss of SSCs in a cell population can be determined with the
      use of a transplantation assay. Defining the mechanisms that regulate the self
      renewal and differentiation of SSCs will fundamentally improve the understanding
      of male fertility and provide information about the regulation of adult stem
      cells in other tissues.

PMID- 20147359
TI  - Getting to grips with health inequalities at last?

PMID- 20147360
TI  - Painless non-itching yellow-white spots on genital mucosa.

PMID- 20147361
TI  - Refeeding syndrome in a patient with anorexia nervosa.

PMID- 20147364
TI  - Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement
      in Schizophrenia.
AB  - The brain concentration of kynurenic acid (KYNA), a metabolite of the kynurenine
      pathway of tryptophan degradation and antagonist at both the glycine coagonist
      site of the N-methyl-D-aspartic acid receptor (NMDAR) and the alpha7 nicotinic
      acetylcholine receptor (alpha7nAChR), is elevated in the prefrontal cortex (PFC)
      of individuals with schizophrenia. This increase may be clinically relevant
      because hypofunction of both the NMDAR and the alpha7nAChR are implicated in the
      pathophysiology, and especially in the cognitive deficits associated with the
      disease. In rat PFC, fluctuations in endogenous KYNA levels bidirectionally
      modulate extracellular levels of 3 neurotransmitters closely related to cognitive
      function (glutamate, dopamine, and acetylcholine). Moreover, behavioral studies
      in rats have demonstrated a causal link between increased cortical KYNA levels
      and neurocognitive deficits, including impairment in spatial working memory,
      contextual learning, sensory gating, and prepulse inhibition of the startle
      reflex. In recent human postmortem studies, impairments in gene expression and
      activity of kynurenine pathway enzymes were found in cortical areas of
      individuals with schizophrenia. Additional studies have revealed an interesting
      association between a sequence variant in the gene of one of these enzymes,
      kynurenine 3-monooxygenase, and neurocognitive deficits seen in patients. The
      emerging, remarkable confluence of data from humans and animals suggests an
      opportunity for developing a rational pharmacology by targeting cortical
      kynurenine pathway metabolism for cognition enhancement in schizophrenia and
      beyond.

PMID- 20147365
TI  - Role of the hypothalamic PVN in the regulation of renal sympathetic nerve
      activity and blood flow during hyperthermia and in heart failure.
AB  - The hypothalamic paraventricular nucleus is a key integrative area in the brain
      involved in influencing sympathetic nerve activity and in the release of hormones
      or releasing factors that contribute to regulating body fluid homeostasis and
      endocrine function. The endocrine and hormonal regulatory function of the
      paraventricular nucleus is well studied, but the regulation of sympathetic nerve
      activity and blood flow by this region is less clear. Here we review the critical
      role of the paraventricular nucleus in regulating renal blood blow during
      hyperthermia and the evidence pointing to an important pathophysiological role of
      the paraventricular nucleus in the elevated renal sympathetic nerve activity that
      is a characteristic of heart failure.

PMID- 20147366
TI  - Vacuolar H+-ATPase apical accumulation in kidney intercalated cells is regulated
      by PKA and AMP-activated protein kinase.
AB  - The vacuolar H(+)-ATPase (V-ATPase) in type A kidney intercalated cells is a
      major contributor to acid excretion in the collecting duct. The mechanisms of V
      ATPase-trafficking regulation in kidney intercalated cells have not been well
      characterized. In developmentally related epididymal clear cells, we showed
      previously that PKA, acting downstream of soluble adenylyl cyclase (sAC), induces
      V-ATPase apical membrane accumulation. These PKA-mediated effects were inhibited
      by activators of the metabolic sensor AMP-activated kinase (AMPK) in clear cells.
      Here, we examined the regulation of V-ATPase subcellular localization in
      intercalated cells by PKA and AMPK in rat kidney tissue slices ex vivo.
      Immunofluorescence labeling of kidney slices revealed that the PKA activator N(6)
      monobutyryl cAMP (6-MB-cAMP) induced V-ATPase apical membrane accumulation in
      collecting duct intercalated cells, whereas the V-ATPase had a more cytosolic
      distribution when incubated in Ringer buffer alone for 30 min. V-ATPase
      accumulated at the apical membrane in intercalated cells in kidney slices
      incubated in Ringer buffer for 75 min, an effect that was prevented by treatment
      with PKA inhibitor (mPKI). The V-ATPase distribution was cytosolic in
      intercalated cells treated with the carbonic anhydrase inhibitor acetazolamide or
      the sAC inhibitor KH7, effects that were overridden by 6-MB-cAMP. Preincubation
      of kidney slices with an AMPK activator blocked V-ATPase apical membrane
      accumulation induced by 6-MB-cAMP, suggesting that AMPK antagonizes cAMP/PKA
      effects on V-ATPase distribution. Taken together, our results suggest that in
      intercalated cells V-ATPase subcellular localization and therefore its activity
      may be coupled to acid-base status via PKA, and metabolic status via AMPK.

PMID- 20147367
TI  - Activation of a latent nuclear localization signal in the NH2 terminus of gamma
      ENaC initiates feedback regulation of channel activity.
AB  - Proteolytic enzymes cleave the epithelial Na(+) channel (ENaC) at several
      positions releasing, in part, the NH(2) terminus of the gamma-subunit. Cleavage
      increases ENaC activity by increasing open probability; however, the role of
      polypeptides cleaved from the channel core remains unclear. We find that the
      cytosolic NH(2) terminus of gamma-ENaC unexpectedly targets to the nucleus being
      particularly strong in nucleoli. In contrast, the cytosolic COOH terminus targets
      to the cytoplasm and plasma membrane in a manner similar to full-length subunits.
      Targeting of the cytosolic NH(2) terminus of gamma-ENaC to the nucleus has
      functional consequences for coexpression of eGFP-fusion proteins containing this
      segment of the channel, but not the COOH terminus, decrease ENaC activity in a
      dose-dependent manner. The mechanism of this negative regulation is associated
      with a decrease in the functional half-life of ENaC at the plasma membrane.
      Inspection of the primary amino acid sequence of gamma-ENaC reveals possible
      nuclear localization signals (NLS) conserved at the extreme NH(2) terminus and
      just preceding the first transmembrane domain. Disruption of the putative NLS
      preceding the first transmembrane domain in gamma-ENaC but not that at the
      extreme NH(2) terminus abolishes both targeting to the nucleus and negative
      regulation of ENaC activity. These findings are consistent with the release of
      the NH(2) terminus of gamma-ENaC following cleavage being functionally important
      for signaling to the nucleus in a manner similar to Notch signaling and release
      of the cytosolic COOH-terminal tail of polycystin-1.

PMID- 20147368
TI  - Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory
      mechanisms of Ca2+ and Mg2+ wasting.
AB  - Claudin-16 (CLDN16) is critical for renal paracellular epithelial transport of
      Ca(2+) and Mg(2+) in the thick ascending loop of Henle. To gain novel insights
      into the role of CLDN16 in renal Ca(2+) and Mg(2+) homeostasis and the
      pathological mechanisms underlying a human disease associated with CLDN16
      dysfunction [familial hypomagnesemia with hypercalciuria and nephrocalcinosis
      (FHHNC), OMIM 248250], we generated a mouse model of CLDN16 deficiency. Similar
      to patients, CLDN16-deficient mice displayed hypercalciuria and hypomagnesemia.
      Contrary to FHHNC patients, nephrocalcinosis was absent in our model, indicating
      the existence of compensatory pathways in ion handling in this model. In line
      with the renal loss of Ca(2+), compensatory mechanisms like parathyroid hormone
      and 1,25(OH)(2)D(3) were significantly elevated. Also, gene expression profiling
      revealed transcriptional upregulation of several Ca(2+) and Mg(2+) transport
      systems including Trpv5, Trpm6, and calbindin-D9k. Induced gene expression was
      also seen for the transcripts of two putative Mg(2+) transport proteins, Cnnm2
      and Atp13a4. Moreover, urinary pH was significantly lower when compared with wild
      type mice. Taken together, our findings demonstrate that loss of CLDN16 activity
      leads to specific alterations in Ca(2+) and Mg(2+) homeostasis and that CLDN16
      deficient mice represent a useful model to further elucidate pathways involved in
      renal Ca(2+) and Mg(2+) handling.

PMID- 20147369
TI  - Unraveling the complex mechanosensory machine of solitary cilia.

PMID- 20147370
TI  - A contribution to identification of novel regulators of plant response to sulfur
      deficiency: characteristics of a tobacco gene UP9C, its protein product and the
      effects of UP9C silencing.
AB  - Extensive changes in plant transcriptome and metabolome have been observed by
      numerous research groups after transferring plants from optimal conditions to
      sulfur (S) deficiency. Despite intensive studies and recent important
      achievements, like identification of SLIM1/EIL3 as a major transcriptional
      regulator of the response to S-deficiency, many questions concerning other
      elements of the regulatory network remain unanswered. Investigations of genes
      with expression regulated by S-deficiency stress encoding proteins of unknown
      function might help to clarify these problems. This study is focused on the UP9C
      gene and the UP9-like family in tobacco. Homologs of these genes exist in other
      plant species, including a family of four genes of unknown function in
      Arabidopsis thaliana (LSU1-4), of which two were reported as strongly induced by
      S-deficit and to a lesser extent by salt stress and nitrate limitation.
      Conservation of the predicted structural features, such as coiled coil region or
      nuclear localization signal, suggests that these proteins might have important
      functions possibly mediated by interactions with other proteins. Analysis of
      transgenic tobacco plants with silenced expression of UP9-like genes strongly
      argues for their significant role in regulation of plant response to S-deficit.
      Although our study shows that the UP9-like proteins are important components of
      such response and they might be also required during other stresses, their
      molecular functions remain a mystery.

PMID- 20147371
TI  - Systemic signaling and local sensing of phosphate in common bean: cross-talk
      between photosynthate and microRNA399.
AB  - Shoot-to-root communication is crucial for plant acclimation to phosphorus (P)
      deficiency. Both sugars and miRNAs have been implicated as potential signal
      molecules transported through phloem from shoot to root for the regulation of
      gene expression and Pi uptake in the root. By studying the expression patterns of
      both a serine/threonine phosphatase gene (PvHAD1) and microRNA399 (miR399) in
      common bean (Phaseolus vulgaris L.), we provide evidence for the interaction
      between light, phloem transport, and miR399 in the systemic regulation of gene
      expression under P-deficiency. Especially, miR399 expression in both the shoot
      and the root requires photosynthetic carbon assimilation during the onset of P
      deficiency. In contrast to systemic signaling, local sensing was the primary
      causal factor for rapid down-regulation of PvHAD1 by Pi prior to the reduction of
      miR399 level in P-deficient roots. Furthermore, this initial response to Pi in P
      deficient root was also mimicked by the Pi analog, phosphonate (Phi). Our current
      findings suggest that plants have developed a highly coordinated dual regulatory
      pathway, namely long-distance signaling of P-deficiency from shoot to root versus
      local sensing of Pi in the root.

PMID- 20147372
TI  - Asymmetrical conspecific seed-siring advantage between Silene latifolia and S.
      dioica.
AB  - BACKGROUND AND AIMS: Silene dioica and S. latifolia experience only limited
      introgression despite overlapping flowering phenologies, geographical
      distributions, and some pollinator sharing. Conspecific pollen precedence and
      other reproductive barriers operating between pollination and seed germination
      may limit hybridization. This study investigates whether barriers at this stage
      contribute to reproductive isolation between these species and, if so, which
      mechanisms are responsible. METHODS: Pollen-tube lengths for pollen of both
      species in styles of both species were compared. Additionally, both species were
      pollinated with majority S. latifolia and majority S. dioica pollen mixes; then
      seed set, seed germination rates and hybridity of the resulting seedlings were
      determined using species-specific molecular markers. KEY RESULTS: The longest
      pollen tubes were significantly longer for conspecific than heterospecific pollen
      in both species, indicating conspecific pollen precedence. Seed set but not seed
      germination was lower for flowers pollinated with pure heterospecific versus pure
      conspecific pollen. Mixed-species pollinations resulted in disproportionately
      high representation of nonhybrid offspring for pollinations of S. latifolia but
      not S. dioica flowers. CONCLUSIONS: The finding of conspecific pollen precedence
      for pollen-tube growth but not seed siring in S. dioica flowers may be explained
      by variation in pollen-tube growth rates, either at different locations in the
      style or between leading and trailing pollen tubes. Additionally, this study
      finds a barrier to hybridization operating between pollination and seed
      germination against S. dioica but not S. latifolia pollen. The results are
      consistent with the underlying cause of this barrier being attrition of S. dioica
      pollen tubes or reduced success of heterospecifically fertilized ovules, rather
      than time-variant mechanisms. Post-pollination, pre-germination barriers to
      hybridization thus play a partial role in limiting introgression between these
      species.

PMID- 20147373
TI  - Making a difference together: reciprocal interactions in C. elegans and zebrafish
      asymmetric neural development.
AB  - Brain asymmetries are thought to increase neural processing capacity and to
      prevent interhemispheric conflict. In order to develop asymmetrically, neurons
      must be specified along the left-right axis, assigned left-side versus right-side
      identities and differentiate appropriately. In C. elegans and zebrafish, the
      cellular and molecular mechanisms that lead to neural asymmetries have recently
      come to light. Here, we consider recent insights into the mechanisms involved in
      asymmetrical neural development in these two species. Although the molecular
      details are divergent, both organisms use iterative cell-cell communication to
      establish left-right neuronal identity.

PMID- 20147374
TI  - Isolation and propagation of enteric neural crest progenitor cells from mouse
      embryonic stem cells and embryos.
AB  - Neural crest is a source of diverse cell types, including the peripheral nervous
      system. The transcription factor Sox10 is expressed throughout early neural
      crest. We exploited Sox10 reporter and selection markers created by homologous
      recombination to investigate the generation, maintenance and expansion of neural
      crest progenitors. Sox10-GFP-positive cells are produced transiently from mouse
      embryonic stem (ES) cells by treatment with retinoic acid in combination with
      Fgf8b and the cytokine leukaemia inhibitory factor (Lif). We found that
      expression of Sox10 can be maintained using noggin, Wnt3a, Lif and endothelin
      (NWLE). ES cell-derived Sox10-GFP-positive cells cultured in NWLE exhibit
      molecular markers of neural crest progenitors. They differentiate into peripheral
      neurons in vitro and are able to colonise the enteric network in organotypic gut
      cultures. Neural crest cells purified from embryos using the Sox10 reporter also
      survive in NWLE, but progressively succumb to differentiation. We therefore
      applied selection to eliminate differentiating cells. Sox10-selected cells could
      be clonally expanded, cryopreserved, and multiplied for over 50 days in adherent
      culture. They remained neurogenic in vitro and in foetal gut grafts. Generation
      of neural crest from mouse ES cells opens a new route to the identification and
      validation of determination factors. Furthermore, the ability to propagate
      undifferentiated progenitors creates an opportunity for experimental dissection
      of the stimuli and molecular circu that govern neural crest lineage progression.
      Finally, the demonstration of robust enteric neurogenesis provides a system for
      investigating and modelling cell therapeutic approaches to neurocristopathies
      such as Hirschsprung's disease.

PMID- 20147376
TI  - FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse
      blastocyst.
AB  - Primitive endoderm (PE) and epiblast (EPI) are two lineages derived from the
      inner cell mass (ICM) of the E3.5 blastocyst. Recent studies showed that EPI and
      PE progenitors expressing the lineage-specific transcriptional factors Nanog and
      Gata6, respectively, arise progressively as the ICM develops. Subsequent sorting
      of the two progenitors during blastocyst maturation results in the ormation of
      morphologically distinct EPI and PE layers at E4.5. It is, however, unknown how
      the initial differences between the two populations become established in the
      E3.5 blastocyst. Because the ICM cells are derived from two distinct rounds of
      polarized cell divisions during cleavage, a possible role for cell lineage
      history in promoting EPI versus PE fate has been proposed. We followed cell
      lineage from the eight-cell stage by live cell tracing and could find no clear
      linkage between developmental history of individual ICM cells and later cell
      fate. However, modulating FGF signaling levels by inhibition of the receptor/MAP
      kinase pathway or by addition of exogenous FGF shifted the fate of ICM cells to
      become either EPI or PE, respectively. Nanog- or Gata6-expressing progenitors
      could still be shifted towards the alternative fate by modulating FGF signaling
      during blastocyst maturation, suggesting that the ICM progenitors are not fully
      committed to their final fate at the time that initial segregation of gene
      expression occurs. In conclusion, we propose a model in which stochastic and
      progressive specification of EPI and PE lineages occurs during maturation of the
      blastocyst in an FGF/MAP kinase signal-dependent manner.

PMID- 20147375
TI  - Transcriptional control of stem cell maintenance in the Drosophila intestine.
AB  - Adult stem cells maintain tissue homeostasis by controlling the proper balance of
      stem cell self-renewal and differentiation. The adult midgut of Drosophila
      contains multipotent intestinal stem cells (ISCs) that self-renew and produce
      differentiated progeny. Control of ISC identity and maintenance is poorly
      understood. Here we find that transcriptional repression of Notch target genes by
      a Hairless-Suppressor of Hairless complex is required for ISC maintenance, and
      identify genes of the Enhancer of split complex [E(spl)-C] as the major targets
      of this repression. In addition, we find that the bHLH transcription factor
      Daughterless is essential to maintain ISC identity and that bHLH binding sites
      promote ISC-specific enhancer activity. We propose that Daughterless-dependent
      bHLH activity is important for the ISC fate and that E(spl)-C factors inhibit
      this activity to promote differentiation.

PMID- 20147377
TI  - COUP-TFs regulate eye development by controlling factors essential for optic
      vesicle morphogenesis.
AB  - Transcriptional networks, which are initiated by secreted proteins, cooperate
      with each other to orchestrate eye development. The establishment of
      dorsal/ventral polarity, especially dorsal specification in the optic vesicle, is
      poorly understood at a molecular and cellular level. Here, we show that COUP-TFI
      (Nr2f1) and COUP-TFII (Nr2f2) are highly expressed in the progenitor cells in the
      developing murine eye. Phenotype analysis of COUP-TFI and COUP-TFII single-gene
      conditional knockout mouse models suggests that COUP-TFs compensate for each
      other to maintain morphogenesis of the eye. However, in eye-specific COUP
      TFI/TFII double-knockout mice, progenitor cells at the dorso-distal optic vesicle
      fail to differentiate appropriately, causing the retinal pigmented epithelium
      cells to adopt a neural retina fate and abnormal differentiation of the dorsal
      optic stalk; the development of proximo-ventral identities, neural retina and
      ventral optic stalk is also compromised. These cellular defects in turn lead to
      congenital ocular colobomata and microphthalmia. Immunohistochemical and in situ
      hybridization assays reveal that the expression of several regulatory genes
      essential for early optic vesicle development, including Pax6, Otx2, Mitf, Pax2
      and Vax1/2, is altered in the corresponding compartments of the mutant eye. Using
      ChIP assay, siRNA treatment and transient transfection in ARPE-19 cells in vitro,
      we demonstrate that Pax6 and Otx2 are directly regulated by COUP-TFs. Taken
      together, our findings reveal novel and distinct cell-intrinsic mechanisms
      mediated by COUP-TF genes to direct the specification and differentiation of
      progenitor cells, and that COUP-TFs are crucial for dorsalization of the eye.

PMID- 20147378
TI  - The PXY-CLE41 receptor ligand pair defines a multifunctional pathway that
      controls the rate and orientation of vascular cell division.
AB  - Controlling the orientation of cell division is fundamental to the development of
      complex body plans. This is particularly apparent in plants, where development is
      determined by differential growth that results solely from changes in cell
      expansion and orientation of the cell division plane. Despite the fundamental
      importance of cell division orientation to plant development, the mechanisms
      regulating this process remain almost completely unknown. During vascular
      development, the meristematic cambial cells divide down their long axis in a
      highly orientated manner to generate clear files of cells. The receptor kinase
      PXY has previously be shown to be essential for this orientation. Here, we
      demonstrate that the division plane is determined by the interactions of PXY and
      its peptide ligand, CLE41. PXY is expressed within dividing meristematic cells of
      the procambium, whereas CLE41 localises to the adjacent phloem cells. Altering
      the pattern of CLE41 expression leads to a loss of cell division orientation and
      a dramatic loss of ordered vascular tissue development. By contrast, increasing
      phloem-specific expression of CLE41 results in more cell divisions, but the
      orientation of cell division is retained, leading to both increased and well
      ordered vascular development. We demonstrate that PXY signalling is down
      regulated by CLE41. This feedback mechanism is crucial in integrating the
      different roles of PXY signalling in controlling xylem differentiation,
      regulating the rate of vascular cell division and determining the orientation of
      cell division. Parallels with animal systems indicate that localised signalling
      from adjacent cells is a general mechanism for defining the plane of cell
      division.

PMID- 20147379
TI  - Sequential requirement of Sox4 and Sox11 during development of the sympathetic
      nervous system.
AB  - The highly related transcription factors Sox4 and Sox11 are expressed in the
      developing sympathetic nervous system. In the mouse, Sox11 appears first, whereas
      Sox4 is prevalent later. Using mouse mutagenesis and overexpression strategies in
      chicken, we studied the role of both SoxC proteins in this tissue. Neither Sox4
      nor Sox11 predominantly functioned by promoting pan-neuronal or noradrenergic
      differentiation of sympathetic neurons as might have been expected from studies
      in neuronal precursors of the central nervous system. The transcriptional network
      that regulates the differentiation of sympathetic neurons remained intact and
      expression of noradrenergic markers showed only minor alterations. Instead, Sox11
      was required in early sympathetic ganglia for proliferation of tyrosine
      hydroxylase-expressing cells, whereas Sox4 ensured the survival of these cells at
      later stages. In the absence of both Sox4 and Sox11, sympathetic ganglia remained
      hypoplastic throughout embryogenesis because of consecutive proliferation and
      survival defects. As a consequence, sympathetic ganglia were rudimentary in the
      adult and sympathetic innervation of target tissues was impaired leading to
      severe dysautonomia.

PMID- 20147380
TI  - Epithelial relaxation mediated by the myosin phosphatase regulator Mypt1 is
      required for brain ventricle lumen expansion and hindbrain morphogenesis.
AB  - We demonstrate that in the zebrafish hindbrain, cell shape, rhombomere
      morphogenesis and, unexpectedly, brain ventricle lumen expansion depend on the
      contractile state of the neuroepithelium. The hindbrain neural tube opens in a
      specific sequence, with initial separation along the midline at rhombomere
      boundaries, subsequent openings within rhombomeres and eventual coalescence of
      openings into the hindbrain ventricle lumen. A mutation in the myosin phosphatase
      regulator mypt1 results in a small ventricle due to impaired stretching of the
      surrounding neuroepithelium. Although initial hindbrain opening remains normal,
      mypt1 mutant rhombomeres do not undergo normal morphological progression. Three
      dimensional reconstruction demonstrates cell shapes within rhombomeres and at
      rhombomere boundaries are abnormal in mypt1 mutants. Wild-type cell shape
      requires that surrounding cells are also wild type, whereas mutant cell shape is
      autonomously regulated. Supporting the requirement for regulation of myosin
      function during hindbrain morphogenesis, wild-type embryos show dynamic levels of
      phosphorylated myosin regulatory light chain (pMRLC). By contrast, mutants show
      continuously high pMRLC levels, with concentration of pMRLC and myosin II at the
      apical side of the epithelium, and myosin II and actin concentration at
      rhombomere boundaries. Brain ventricle lumen expansion, rhombomere morphology and
      cell shape are rescued by inhibition of myosin II function, indicating that each
      defect is a consequence of overactive myosin. We suggest that the epithelium must
      ;relax', via activity of myosin phosphatase, to allow for normal hindbrain
      morphogenesis and expansion of the brain ventricular lumen. Epithelial relaxation
      might be a widespread strategy to facilitate tube inflation in many organs.

PMID- 20147381
TI  - Cadherin-7 and cadherin-6B differentially regulate the growth, branching and
      guidance of cranial motor axons.
AB  - Cadherin-7 (Cad7) and cadherin-6B (Cad6B) are expressed in early and late phases
      of cranial motoneuron development, respectively. Cad7 is expressed by cranial
      motoneurons soon after they are generated, as well as in the environment through
      which their axons extend. By contrast, Cad6B is expressed by mature cranial
      motoneurons. We demonstrate in chick that these cadherins play distinct roles in
      cranial motor axon morphology, branching and projection. Using in vitro
      approaches, we show that Cad7 enhances motor axon outgrowth, suppresses the
      formation of multiple axons and restricts interstitial branching, thus promoting
      the development of a single unbranched axon characteristic of differentiating
      motoneurons. Conversely, Cad6B in vitro promotes motor axon branching, a
      characteristic of mature motoneurons. In vivo gain- and loss-of-function
      experiments for these cadherins yielded phenotypes consistent with this
      interpretation. In particular, a loss of cadherin-mediated interactions in vivo
      led to dysregulation of the cranial motoneuron normal branching programme and
      caused axon navigation defects. We also demonstrate that Cad6B functions via the
      phosphatidylinositol 3-kinase pathway. Together, these data show that Cad7 and
      Cad6B differentially regulate cranial motoneuron growth, branching and axon
      guidance.

PMID- 20147382
TI  - lethal giant larvae is required with the par genes for the early polarization of
      the Drosophila oocyte.
AB  - Most cell types in an organism show some degree of polarization, which relies on
      a surprisingly limited number of proteins. The underlying molecular mechanisms
      depend, however, on the cellular context. Mutual inhibitions between members of
      the Par genes are proposed to be sufficient to polarize the C. elegans one-cell
      zygote and the Drosophila oocyte during mid-oogenesis. By contrast, the Par genes
      interact with cellular junctions and associated complexes to polarize epithelial
      cells. The Par genes are also required at an early step of Drosophila oogenesis
      for the maintenance of the oocyte fate and its early polarization. Here we show
      that the Par genes are not sufficient to polarize the oocyte early and that the
      activity of the tumor-suppressor gene lethal giant larvae (lgl) is required for
      the posterior translocation of oocyte-specific proteins, including germline
      determinants. We also found that Lgl localizes asymmetrically within the oocyte
      and is excluded from the posterior pole. We further demonstrate that
      phosphorylation of Par-1, Par-3 (Bazooka) and Lgl is crucial to regulate their
      activity and localization in vivo and describe, for the first time, adherens
      junctions located around the ring canals, which link the oocyte to the other
      cells of the germline cyst. However, null mutations in the DE-cadherin gene,
      which encodes the main component of the zonula adherens, do not affect the early
      polarization of the oocyte. We conclude that, despite sharing many similarities
      with other model systems at the genetic and cellular levels, the polarization of
      the early oocyte relies on a specific subset of polarity proteins.

PMID- 20147383
TI  - Signaling via Alk5 controls the ontogeny of lung Clara cells.
AB  - Clara cells, together with ciliated and pulmonary neuroendocrine cells, make up
      the epithelium of the bronchioles along the conducting airways. Clara cells are
      also known as progenitor or stem cells during lung regeneration after injury. The
      mechanisms of Clara cell differentiation are largely unknown. Transforming growth
      factor beta (TGFbeta)is a multifunctional molecule with roles in normal
      development and disease pathogenesis. In this study, we deleted the TGFbeta type
      I receptor Alk5 in the embryonic lung epithelium using Gata5-Cre mice. Absence of
      Alk5 blocked Clara cell differentiation but had no effect on ciliated or
      pulmonary neuroendocrine cells. Hairy/Enhancer of Split-1, which is expressed in
      Clara cell putative ;progenitors' was found to be a downstream target of Alk5 in
      vivo and in vitro. Loss of Alk5-mediated signaling also stimulated Pten gene
      expression and inhibited ERK phosphorylation in vivo. Using lung epithelial
      cells, we show that Alk5-regulated Hes1 expression is stimulated through Pten and
      the MEK/ERK and PI3K/AKT pathways. Thus, the signaling pathway by which
      TGFbeta/ALK5 regulates Clara cell differentiation may entail inhibition of Pten
      expression, which in turn activates ERK and AKT phosphorylation.

PMID- 20147384
TI  - giant is a bona fide gap gene in the intermediate germband insect, Oncopeltus
      fasciatus.
AB  - Drosophila undergoes a form of development termed long germ segmentation, where
      all segments are specified nearly simultaneously so that by the blastoderm stage,
      the entire body plan has been determined. This mode of segmentation is
      evolutionarily derived. Most insects undergo short or intermediate germ
      segmentation, where only anterior segments are specified early, and posterior
      segments are sequentially specified during germband elongation. These
      embryological differences imply that anterior and posterior segments might rely
      upon different molecular mechanisms. In Drosophila, embryos mutant for giant show
      a gap in the anterior as well fusions of several abdominal segments. In
      Tribolium, a short germ beetle, giant is required for segmental identity, but not
      formation, in gnathal segments and also for segmentation of the entire abdomen.
      This raises the possibility that giant might not act as a gap gene in short and
      intermediate germ insects. Oncopeltus fasciatus is an intermediate germ insect
      that is an outgroup to the clade containing Drosophila and Tribolium. We cloned
      the Oncopeltus homolog of giant and determined its expression and function during
      segmentation. We find that Oncopeltus giant is a canonical gap gene in the
      maxillary and labial segments and also plays a gap-like role in the first four
      abdominal segments. Our results suggest that giant was a bona fide gap gene in
      the ancestor of these insects with this role being lost in the lineage leading
      towards Tribolium. This highlights the conservation of anterior patterning and
      evolutionary plasticity of the genetic regulation controlling posterior
      segmentation, even in short and intermediate germ insects.

PMID- 20147385
TI  - Sexual intercourse and high-risk sexual behaviours among a national sample of
      urban adolescents in China.
AB  - BACKGROUND: To describe the characteristics of a population with high-risk sexual
      behaviours and associations between sexual intercourse, high-risk sexual
      behaviours and socio-demographic characteristics among Chinese urban adolescents.
      METHODS: In 2005, 109,754 students in grades 10-12 and 33,653 college students
      were anonymously surveyed using a Chinese Youth Risk Behaviour Survey.
      Demographic variables and indicators of forced sex, condom use and unintended
      pregnancy were analysed with multiple logistic regressions. RESULTS: Of students
      surveyed, median age was 17.6 (range 14-24 years) and 76,233 were female (53.2%);
      4.8% of high school students reported had experienced sexual intercourse; of
      these, 32.8% reported had forced sex; 11.3% of college students reported had
      experienced sexual intercourse and of these, the prevalence of forced sex, condom
      use and unintended pregnancy were 23.5, 49.7 and 24.2%, respectively. School type
      and socioeconomic status were found to be independently associated with sexual
      intercourse and forced sex for high school students. For college students,
      educational level, school type, family structure, maternal education and
      socioeconomic status were independently associated with high-risk sexual
      behaviours. CONCLUSION: This study highlights the association between high-risk
      sexual behaviours and school type and socioeconomic status. These results
      strongly suggest the importance of providing sex education in high schools and
      lower socioeconomic areas.

PMID- 20147386
TI  - Evaluating imaging systems: practical applications.
AB  - There are many ways in which imaging systems can be evaluated. The aim of the
      present paper is to provide an overview of a number of selected approaches to
      evaluating imaging systems, often encountered by the medical physicist, and
      discuss their validity and reliability. Specifically, it will cover (i)
      characterisation of an imaging system in terms of its detective quantum
      efficiency using linear-systems analysis; (ii) attempts to calculate relevant
      measures directly in images using the Rose model and the pixel signal-to-noise
      ratio; (iii) task-based methods incorporating human observers such as receiver
      operating characteristics and (iv) visual grading-based methods using experienced
      radiologists as observers.

PMID- 20147387
TI  - Simian virus 40 T/t antigens and lamin A/C small interfering RNA rescue the
      phenotype of an Epstein-Barr virus protein kinase (BGLF4) mutant.
AB  - The Epstein-Barr virus (EBV)-encoded viral protein kinase, EBV-PK (the BGLF4 gene
      product), is required for efficient nuclear viral egress in 293 cells. However,
      since EBV-PK phosphorylates a number of different viral and cellular proteins
      (including lamin A/C), the relative importance of each target during lytic viral
      replication remains unclear. We show here that an EBV PK mutant (PKmut;
      containing stop codons at residues 1 and 5 in EBV-PK) is highly defective for
      release of infectious virus from 293 cells but not 293T cells. Furthermore, the
      phenotype of the PKmut in 293 cells is substantially reversed by expression of
      the simian virus 40 (SV40) large (T) and small (t) T antigens. Efficient rescue
      requires the presence of both SV40 T/t proteins. We show that 293T cells have a
      much higher level of constitutive lamin A/C phosphorylation than do 293 cells
      over residues (S22 and S392) that promote phosphorylation-dependent nuclear
      disassembly and that both large T and small t contribute to enhanced lamin A/C
      phosphorylation. Finally, we demonstrate that knockdown of lamin A/C expression
      using small interfering RNA also rescues the PKmut phenotype in 293 cells. These
      results suggest that essential roles of EBV-PK during lytic viral replication
      include the phosphorylation and dispersion of lamin A/C.

PMID- 20147388
TI  - Stimulation of HIV-1 replication in immature dendritic cells in contact with
      primary CD4 T or B lymphocytes.
AB  - Sexual transmission is the major route of HIV-1 infection worldwide. Dendritic
      cells (DCs) from the mucosal layers are considered to be the initial targets of
      HIV-1 and probably play a crucial role in HIV-1 transmission. We investigated the
      role of cell-to-cell contact between HIV-1-exposed immature DCs and various
      lymphocyte subsets in the stimulation of HIV-1 replication. We found that HIV-1
      replication and production in DCs were substantially enhanced by the coculture of
      DCs with primary CD4 T or nonpermissive B lymphocytes but not with primary
      activated CD8 T lymphocytes or human transformed CD4 T lymphocytes. Most of the
      new virions released by cocultures of HIV-1-exposed immature DCs and primary B
      lymphocytes expressed the DC-specific marker CD1a and were infectious for both
      immature DCs and peripheral blood mononuclear cells (PBMCs). Cocultured DCs thus
      produced large numbers of infectious viral particles under these experimental
      conditions. The soluble factors present in the supernatants of the cocultures
      were not sufficient to enhance HIV-1 replication in DCs, for which cell-to-cell
      contact was required. The neutralizing monoclonal antibody IgG1b12 and polyclonal
      anti-HIV-1 sera efficiently blocked HIV-1 transfer to CD4 T lymphocytes but did
      not prevent the increase in viral replication in DCs. Neutralizing antibodies
      thus proved to be more efficient at blocking HIV-1 transfer than previously
      thought. Our findings show that HIV-1 exploits DC-lymphocyte cross talk to
      upregulate replication within the DC reservoir. We provide evidence for a novel
      mechanism that may facilitate HIV-1 replication and transmission. This mechanism
      may favor HIV-1 pathogenesis, immune evasion, and persistence.

PMID- 20147389
TI  - CD317/tetherin is enriched in the HIV-1 envelope and downregulated from the
      plasma membrane upon virus infection.
AB  - CD317/Bst-2/tetherin is a host factor that restricts the release of human
      immunodeficiency virus type 1 (HIV-1) by trapping virions at the plasma membrane
      of certain producer cells. It is antagonized by the HIV-1 accessory protein Vpu.
      Previous light microscopy studies localized CD317 to the plasma membrane and the
      endosomal compartment and showed Vpu induced downregulation. In the present
      study, we performed quantitative immunoelectron microscopy of CD317 in cells
      producing wild-type or Vpu-defective HIV-1 and in control cells. Double-labeling
      experiments revealed that CD317 localizes to the plasma membrane, to early and
      recycling endosomes, and to the trans-Golgi network. CD317 largely relocated to
      endosomes upon HIV-1 infection, and this effect was partly counteracted by Vpu.
      Unexpectedly, CD317 was enriched in the membrane of viral buds and cell
      associated and cell-free viruses compared to the respective plasma membrane, and
      this enrichment was independent of Vpu. These results suggest that the tethering
      activity of CD317 critically depends on its density at the cell surface and
      appears to be less affected by its density in the virion membrane.

PMID- 20147390
TI  - Viral dynamics during primary simian immunodeficiency virus infection: effect of
      time-dependent virus infectivity.
AB  - A recent experiment involving simian immunodeficiency virus (SIV) infection of
      macaques revealed that the infectivity of this virus decreased over the first few
      months of infection. Based on this observation, we introduce a viral dynamic
      model in which viral infectivity varies over time. The model is fit to viral load
      data from eight (donor) monkeys infected by intravaginal inoculation of
      SIVmac251, three monkeys infected by intravenous inoculation of virus isolated
      from the donors during the ramp-up phase of acute infection, and three monkeys
      infected by intravenous inoculation of virus isolated at the viral set-point.
      Although we only analyze data from 14 monkeys, the new model with time-dependent
      infectivity seems to fit the data significantly better than a widely used model
      with constant infectivity (P = 2.44 x 10(-11)). Our results indicate that plasma
      virus infectivity on average decays approximately 8-fold (95% confidence interval
      [CI] = 5.1 to 10.3) over the course of acute infection, with the decay occurring
      exponentially with an average rate of 0.28 day(-1) (95% CI = 0.14 to 0.42 day(
      1)). The decay rate in set point plasma virus recipient animals is approximately
      16 times slower than in ramp-up plasma virus recipient animals and approximately
      6 times slower than in donor animals. Throughout acute infection up to the set
      point, the infection rate is higher in ramp-up plasma virus recipient animals
      than in set-point plasma virus recipient animals. These results show that the
      infectivity depends upon the source of viral infection.

PMID- 20147391
TI  - CD147/EMMPRIN acts as a functional entry receptor for measles virus on epithelial
      cells.
AB  - Measles is a highly contagious human disease caused by measles virus (MeV) and
      remains the leading cause of death in children, particularly in developing
      countries. Wild-type MeV preferentially infects lymphocytes by using signaling
      lymphocytic activation molecule (SLAM), whose expression is restricted to
      hematopoietic cells, as a receptor. MeV also infects other epithelial and
      neuronal cells that do not express SLAM and causes pneumonia and diarrhea and,
      sometimes, serious symptoms such as measles encephalitis and subacute sclerosing
      panencephalitis. The discrepancy between the tissue tropism of MeV and the
      distribution of SLAM-positive cells suggests that there are unknown receptors
      other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix
      metalloproteinase inducer), a transmembrane glycoprotein, which acts as a
      receptor for MeV on epithelial cells. Furthermore, we found the incorporation of
      cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed
      that inhibition of CypB incorporation significantly attenuated SLAM-independent
      infection on epithelial cells, while it had no effect on SLAM-dependent
      infection. To date, MeV infection was considered to be triggered by binding of
      its hemagglutinin (H) protein and cellular receptors. Our present study, however,
      indicates that MeV infection also occurs via CD147 and virion-associated CypB,
      independently of MeV H. Since CD147 is expressed in a variety of cells, including
      epithelial and neuronal cells, this molecule possibly functions as an entry
      receptor for MeV in SLAM-negative cells. This is the first report among members
      of the Mononegavirales that CD147 is used as a virus entry receptor via
      incorporated CypB in the virions.

PMID- 20147392
TI  - Polyubiquitination of APOBEC3G is essential for its degradation by HIV-1 Vif.
AB  - Proteasomal degradation of APOBEC3G is a critical step for human immunodeficiency
      virus type 1 (HIV-1) replication. However, the necessity for polyubiquitination
      of APOBEC3G in this process is still controversial. In this study, we showed that
      although macaque simian immunodeficiency virus (SIVmac) Vif is more stable than
      HIV-1 Vif in human cells, SIVmac Vif induces degradation of APBOEC3G as
      efficiently as HIV-1 Vif. Overexpression of APOBEC3G or lysine-free APOBEC3G
      stabilized HIV-1 Vif, indicating that APOBEC3G degradation is independent of the
      degradation of Vif. Furthermore, an in vivo polyubiquitination assay showed that
      lysine-free APOBEC3G was also polyubiquitinated. These data suggest that
      polyubiquitination of APOBEC3G, not that of HIV-1 Vif, is crucial for APOBEC3G
      degradation.

PMID- 20147393
TI  - T cells engineered with a cytomegalovirus-specific chimeric immunoreceptor.
AB  - Cytomegalovirus (CMV) infection in patients receiving hematopoietic stem cell
      transplants (HSCT) is associated with morbidity and mortality. Adoptive T cell
      immunotherapy has been used to treat viral reactivation but is hardly feasible in
      high-risk constellations of CMV-positive HSCT patients and CMV-negative stem cell
      donors. We endowed human effector T cells with a chimeric immunoreceptor (cIR)
      directed against CMV glycoprotein B. These cIR-engineered primary T cells
      mediated antiviral effector functions such as cytokine production and cytolysis.
      This first description of cIR-redirected CMV-specific T cells opens up a new
      perspective for HLA-independent immunotherapy of CMV infection in high-risk
      patients.

PMID- 20147395
TI  - Antagonism of CD317 restriction of human immunodeficiency virus type 1 (HIV-1)
      particle release and depletion of CD317 are separable activities of HIV-1 Vpu.
AB  - Vpu antagonizes human immunodeficiency virus type 1 (HIV-1) particle release
      inhibition by CD317/BST-2/Tetherin. Whether this Vpu activity strictly requires
      cellular depletion of the restriction factor is unclear. Here, we characterized
      CD317 variants with mutations in putative sorting or ubiquitination motifs. All
      mutants still potently impaired release of Vpu-defective HIV-1 and remained
      sensitive to Vpu-mediated release enhancement. Importantly, this virological
      antagonism correlated with surface downregulation of CD317 mutants by Vpu, while
      intracellular pools of these mutants, which were consistently depleted of the
      wild-type protein, were highly variable or even enhanced. Thus, Vpu can
      efficiently antagonize virion tethering in the absence of CD317 degradation.

PMID- 20147394
TI  - Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a
      general strategy to interfere with actin remodeling.
AB  - Nef is an accessory protein and pathogenicity factor of human immunodeficiency
      virus (HIV) and simian immunodeficiency virus (SIV) which elevates virus
      replication in vivo. We recently described for HIV type 1(SF2) (HIV-1(SF2)) the
      potent interference of Nef with T-lymphocyte chemotaxis via its association with
      the cellular kinase PAK2. Mechanistic analysis revealed that this interaction
      results in deregulation of the actin-severing factor cofilin and thus blocks the
      chemokine-mediated actin remodeling required for cell motility. However, the
      efficiency of PAK2 association is highly variable among Nef proteins from
      different lentiviruses, prompting us to evaluate the conservation of this actin
      remodeling/cofilin-deregulating mechanism. Based on the analysis of a total of 17
      HIV-1, HIV-2, and SIV Nef proteins, we report here that inhibition of chemokine
      induced actin remodeling as well as inactivation of cofilin are strongly
      conserved activities of lentiviral Nef proteins. Of note, even for Nef variants
      that display only marginal PAK2 association in vitro, these activities require
      the integrity of a PAK2 recruitment motif and the presence of endogenous PAK2.
      Thus, reduced in vitro affinity to PAK2 does not indicate limited functionality
      of Nef-PAK2 complexes in intact HIV-1 host cells. These results establish
      hijacking of PAK2 for deregulation of cofilin and inhibition of triggered actin
      remodeling as a highly conserved function of lentiviral Nef proteins, supporting
      the notion that PAK2 association may be critical for Nef's activity in vivo.

PMID- 20147396
TI  - Generation of the pathogenic R5-tropic simian/human immunodeficiency virus
      SHIVAD8 by serial passaging in rhesus macaques.
AB  - A new pathogenic R5-tropic simian/human immunodeficiency virus (SHIV) was
      generated following serial passaging in rhesus macaques. All 13 animals
      inoculated with SHIV(AD8) passaged lineages experienced marked depletions of
      CD4(+) T cells. Ten of these infected monkeys became normal progressors (NPs) and
      had gradual losses of both memory and naive CD4(+) T lymphocytes, generated
      antiviral CD4(+) and CD8(+) T cell responses, and sustained chronic immune
      activation while maintaining variable levels of plasma viremia (10(2) to 10(5)
      RNA copies/ml for up to 3 years postinfection [p.i.]). To date, five NPs
      developed AIDS associated with opportunistic infections caused by Pneumocystis
      carinii, Mycobacterium avium, and Campylobacter coli that required euthanasia
      between weeks 100 and 199 p.i. Three other NPs have experienced marked depletions
      of circulating CD4(+) T lymphocytes (92 to 154 cells/microl) following 1 to 2
      years of infection. When tested for coreceptor usage, the viruses isolated from
      four NPs at the time of their euthanasia remained R5 tropic. Three of the 13
      SHIV(AD8)-inoculated macaques experienced a rapid-progressor syndrome
      characterized by sustained plasma viremia of >1 x 10(7) RNA copies/ml and rapid
      irreversible loss of memory CD4(+) T cells that required euthanasia between weeks
      19 and 23 postinfection. The sustained viremia, associated depletion of CD4(+) T
      lymphocytes, and induction of AIDS make the SHIV(AD8) lineage of viruses a
      potentially valuable reagent for vaccine studies.

PMID- 20147397
TI  - Virus-specific CD8+ T-cell responses better define HIV disease progression than
      HLA genotype.
AB  - HLA alleles B57/58, B27, and B35 have the strongest genetic associations with HIV
      1 disease progression. The mechanisms of these relationships may be host control
      of HIV-1 infection via CD8(+) T-cell responses. We examined these immune
      responses in subjects from the Seattle Primary Infection Cohort with these
      alleles. CD8(+) T-cell responses to conserved HIV epitopes within B57/58 alleles
      (TW10 and KF11) and B27 alleles (KK10 and FY10) delayed declines in CD4(+) T-cell
      counts (4 to 8 times longer), while responses to variable epitopes presented by
      B35 alleles (DL9 and IL9) resulted in more rapid progression. The plasma viral
      load was higher in B57/58(+) and B27(+) subjects lacking the conserved B57/58-
      and B27-restricted responses. The presence of certain B57/58-, B27-, and B35
      restricted HIV-specific CD8(+) T-cell responses after primary HIV-1 infection
      better defined disease progression than the HLA genotype alone, suggesting that
      it is the HIV-specific CD8(+) T cells and not the presence of a particular HLA
      allele that determine disease progression. Further, the most effective host
      CD8(+) T-cell responses to HIV-1 were prevalent within an HLA allele, represented
      a high total allele fraction of the host CD8(+) T-cell response, and targeted
      conserved regions of HIV-1. These data suggest that vaccine immunogens should
      contain only conserved regions of HIV-1.

PMID- 20147398
TI  - Donor and recipient envs from heterosexual human immunodeficiency virus subtype C
      transmission pairs require high receptor levels for entry.
AB  - Compact, glycan-restricted envelope (Env) glycoproteins are selected during
      heterosexual transmission of subtype C HIV-1. Donor and recipient glycoproteins
      (Envs) from six transmission pairs were evaluated for entry into HeLa cells
      expressing different levels of CD4 and CCR5. Donor and recipient Envs
      demonstrated efficient entry into cells expressing high levels of CD4 and CCR5,
      and entry declined as CCR5 levels decreased. Infectivity for all Envs was
      severely impaired in cells expressing low levels of CD4, even at the highest CCR5
      levels. In 5/6 pairs, there was no significant difference in efficiency of
      receptor utilization between the donor and recipient Envs in these HeLa-derived
      cell lines. Thus, HIV-1 transmission does not appear to select for viruses that
      can preferentially utilize low levels of entry receptors.

PMID- 20147399
TI  - Regulation of ICP0-null mutant herpes simplex virus type 1 infection by ND10
      components ATRX and hDaxx.
AB  - Herpes simplex virus type 1 (HSV-1) immediate-early gene product ICP0 activates
      lytic infection and relieves cell-mediated repression of viral gene expression.
      This repression is conferred by preexisting cellular proteins and is commonly
      referred to as intrinsic antiviral resistance or intrinsic defense. PML and
      Sp100, two core components of nuclear substructures known as ND10 or PML nuclear
      bodies, contribute to intrinsic resistance, but it is clear that other proteins
      must also be involved. We have tested the hypothesis that additional ND10
      factors, particularly those that are involved in chromatin remodeling, may have
      roles in intrinsic resistance against HSV-1 infection. The two ND10 component
      proteins investigated in this report are ATRX and hDaxx, which are known to
      interact with each other and comprise components of a repressive chromatin
      remodeling complex. We generated stable cell lines in which endogenous ATRX or
      hDaxx expression is severely suppressed by RNA interference. We found increases
      in both gene expression and plaque formation induced by ICP0-null mutant HSV-1 in
      both ATRX- and hDaxx-depleted cells. Reconstitution of wild-type hDaxx expression
      reversed the effects of hDaxx depletion, but reconstitution with a mutant form of
      hDaxx unable to interact with ATRX did not. Our results suggest that ATRX and
      hDaxx act as a complex that contributes to intrinsic antiviral resistance to HSV
      1 infection, which is counteracted by ICP0.

PMID- 20147400
TI  - Herpes simplex virus glycoproteins H/L bind to cells independently of
      {alpha}V{beta}3 integrin and inhibit virus entry, and their constitutive
      expression restricts infection.
AB  - Herpes simplex virus (HSV) fusion with cells requires the gD, gB, and gH/gL
      glycoprotein quartet. gD serves as a receptor binding glycoprotein. gB and gH/gL
      execute fusion in an as-yet-unclear manner. To better understand the role of
      gH/gL in HSV entry, we produced a soluble version of gH/gL carrying a One-STrEP
      tag (gH(t.st)/gL). Previous findings implicated integrins as possible ligands to
      gH/gL (C. Parry et al., J. Gen. Virol. 86:7-10, 2005). We report that (i)
      gH(t.st)/gL bound a number of cells in a dose-dependent manner at concentrations
      similar to those required for the binding of soluble gB or gD. (ii) gH(t.st)/gL
      inhibited HSV entry at the same concentrations required for binding. It also
      inhibited cell-cell fusion in transfected cells. (iii) The absence of beta3
      integrin did not prevent the binding of gH(t.st)/gL to CHO cells and infection
      inhibition. Conversely, integrin-negative K562 cells did not acquire the ability
      to bind gH(t.st)/gL when hyperexpressing alphaVbeta3 integrin. (iv) Constitutive
      expression of wild-type gH/gL (wt-gH/gL) restricted infection in all of the cell
      lines tested, a behavior typical of glycoproteins which bind cellular receptors.
      The extent of restriction broadly paralleled the efficiency of gH/gL
      transfection. RGD motif mutant gH/gL could not be differentiated from wt-gH with
      respect to restriction of infection. Cumulatively, the present results provide
      several lines of evidence that HSV gH/gL interacts with a cell surface cognate
      protein(s), that this protein is not necessarily an alphaVbeta3 integrin, and
      that this interaction is required for the process of virus entry/fusion.

PMID- 20147401
TI  - Venezuelan equine Encephalitis virus capsid protein forms a tetrameric complex
      with CRM1 and importin alpha/beta that obstructs nuclear pore complex function.
AB  - Development of the cellular antiviral response requires nuclear translocation of
      multiple transcription factors and activation of a wide variety of cellular
      genes. To counteract the antiviral response, several viruses have developed an
      efficient means of inhibiting nucleocytoplasmic traffic. In this study, we
      demonstrate that the pathogenic strain of Venezuelan equine encephalitis virus
      (VEEV) has developed a unique mechanism of nuclear import inhibition. Its capsid
      protein forms a tetrameric complex with the nuclear export receptor CRM1 and the
      nuclear import receptor importin alpha/beta. This unusual complex accumulates in
      the center channel of the nuclear pores and blocks nuclear import mediated by
      different karyopherins. The inhibitory function of VEEV capsid protein is
      determined by a short 39-amino-acid-long peptide that contains both nuclear
      import and supraphysiological nuclear export signals. Mutations in these signals
      or in the linker peptide attenuate or completely abolish capsid-specific
      inhibition of nuclear traffic. The less pathogenic VEEV strains contain a wide
      variety of mutations in this peptide that affect its inhibitory function in
      nuclear import. Thus, these mutations appear to be the determinants of this
      attenuated phenotype. This novel mechanism of inhibiting nuclear transport also
      shows that the nuclear pore complex is vulnerable to unusual cargo receptor
      complexes and sheds light on the importance of finely adjusted karyopherin
      nucleoporin interactions for efficient cargo translocation.

PMID- 20147402
TI  - Mechanisms responsible for a PhiX174 mutant's ability to infect Escherichia coli
      by phosphorylation.
AB  - The ability for a virus to expand its host range is dependent upon a successful
      mode of viral entry. As such, the host range of the well-studied PhiX174
      bacteriophage is dictated by the presence of a particular lipopolysaccharide
      (LPS) on the bacterial surface. The mutant PhiX174 strain JACS-K, unlike its
      ancestor, is capable of infecting both its native host Escherichia coli C and E.
      coli K-12, which does not have the necessary LPS. The conversion of an alanine to
      a very reactive threonine on its virion surface was found to be responsible for
      the strain's expanded host range.

PMID- 20147403
TI  - Structure-based mutational analysis of the bovine papillomavirus E1 helicase
      domain identifies residues involved in the nonspecific DNA binding activity
      required for double trimer formation.
AB  - The papillomavirus E1 protein is a multifunctional initiator protein responsible
      for preparing the viral DNA template for initiation of DNA replication. The E1
      protein encodes two DNA binding activities that are required for initiation of
      DNA replication. A well-characterized sequence-specific DNA binding activity
      resides in the E1 DBD and is used to tether E1 to the papillomavirus ori. A non
      sequence-specific DNA binding activity is also required for formation of the E1
      double trimer (DT) complex, which is responsible for the local template melting
      that precedes loading of the E1 helicase. This DNA binding activity is very
      poorly understood. We use a structure-based mutagenesis approach to identify
      residues in the E1 helicase domain that are required for the non-sequence
      specific DNA binding and DT formation. We found that three groups of residues are
      involved in nonspecific DNA binding: the E1 beta-hairpin structure containing
      R505, K506, and H507; a hydrophobic loop containing F464; and a charged loop
      containing K461 together generate the binding surface involved in nonspecific DNA
      binding. These residues are well conserved in the T antigens from the
      polyomaviruses, indicating that the polyomaviruses share this nonspecific DNA
      binding activity.

PMID- 20147404
TI  - Ablation of the complementarity-determining region H3 apex of the anti-HIV-1
      broadly neutralizing antibody 2F5 abrogates neutralizing capacity without
      affecting core epitope binding.
AB  - The identification and characterization of broadly neutralizing antibodies
      (bnAbs) against HIV-1 has formed a major research focus, with the ultimate goal
      to help in the design of an effective AIDS vaccine. One of these bnAbs, 2F5, has
      been extensively characterized, and residues at the apex of its unusually long
      complementarity-determining region (CDR) H3 loop have been shown to be crucial
      for neutralization. Structural studies, however, have revealed that the
      (100)TLFGVPI(100F) apex residues of the CDR H3 loop do not interact directly with
      residues of its core gp41 epitope. In an attempt to gain better insight into the
      functional role of this element, we have recombinantly expressed native 2F5 Fab
      and two mutants in which either the apical Phe100B(H) residue was changed to an
      alanine or the CDR H3 residues (100)TLFGVPI(100F) were replaced by a Ser-Gly
      dipeptide linker. Isothermal titration calorimetry (ITC) and competitive-binding
      enzyme-linked immunosorbent assays (ELISAs) rendered strikingly similar affinity
      constants (K(d) [dissociation constant] of approximately 20 nM) for linear
      peptide epitope binding by 2F5 Fabs, independent of the presence or absence of
      the apex residues. Ablation of the CDR H3 apex residues, however, abolished the
      cell-cell fusion inhibition and pseudovirus neutralization capacities of 2F5 Fab.
      We report competitive ELISA data that suggest a role of 2F5 CDR H3 apex residues
      in mediating weak hydrophobic interactions with residues located at the C
      terminus of the gp41 membrane proximal external region and/or membrane components
      in the context of core epitope binding. The present data therefore imply an
      extended 2F5 paratope that includes weak secondary interactions that are crucial
      for neutralization of Env-mediated fusion.

PMID- 20147405
TI  - Type I interferon-sensitive recombinant newcastle disease virus for oncolytic
      virotherapy.
AB  - Newcastle disease virus (NDV), an avian paramyxovirus, is tumor selective and
      intrinsically oncolytic because of its potent ability to induce apoptosis.
      Several studies have demonstrated that NDV is selectively cytotoxic to tumor
      cells but not normal cells due to defects in the interferon (IFN) antiviral
      responses of tumor cells. Many naturally occurring strains of NDV have an intact
      IFN-antagonistic function and can still replicate in normal human cells. To avoid
      potential toxicity issues with NDV, especially in cancer patients with
      immunosuppression, safe NDV-oncolytic vectors are needed. We compared the cell
      killing abilities of (i) a recombinant NDV (rNDV) strain, Beaudette C, containing
      an IFN-antagonistic, wild-type V protein (rBC), (ii) an isogenic recombinant
      virus with a mutant V protein (rBC-Edit virus) that induces increased IFN in
      infected cells and whose replication is restricted in normal human cells, and
      (iii) a recombinant LaSota virus with a virulent F protein cleavage site that is
      as interferon sensitive as rBC-Edit virus (LaSota V.F. virus). Our results
      indicated that the tumor-selective replication of rNDV is determined by the
      differential regulation of IFN-alpha and downstream antiviral genes induced by
      IFN-alpha, especially through the IRF-7 pathway. In a nude mouse model of human
      fibrosarcoma, we show that the IFN-sensitive NDV variants are as effective as IFN
      resistant rBC virus in clearing the tumor burden. In addition, mice treated with
      rNDV exhibited no signs of toxicity to the viruses. These findings indicate that
      augmentation of innate immune responses by NDV results in selective oncolysis and
      offer a novel and safe virotherapy platform.

PMID- 20147406
TI  - A novel inhibitor of the NF-{kappa}B signaling pathway encoded by the
      parapoxvirus orf virus.
AB  - The parapoxvirus orf virus (ORFV) is a pathogen of sheep and goats that has been
      used as a preventive and therapeutic immunomodulatory agent in several animal
      species. However, the functions (genes, proteins, and mechanisms of action)
      evolved by ORFV to modulate and manipulate immune responses are poorly
      understood. Here, the novel ORFV protein ORFV024 was shown to inhibit activation
      of the NF-kappaB signaling pathway, an important modulator of early immune
      responses against viral infections. Infection of primary ovine cells with an
      ORFV024 deletion mutant virus resulted in a marked increase in expression of NF
      kappaB-regulated chemokines and other proinflammatory host genes. Expression of
      ORFV024 in cell cultures significantly decreased lipopolysaccharide (LPS)- and
      tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB-responsive reporter
      gene expression. Further, ORFV024 expression decreased TNF-alpha-induced
      phosphorylation and nuclear translocation of NF-kappaB-p65, phosphorylation, and
      degradation of IkappaBalpha, and phosphorylation of IkappaB kinase (IKK) subunits
      IKKalpha and IKKbeta, indicating that ORFV024 functions by inhibiting activation
      of IKKs, the bottleneck for most NF-kappaB activating stimuli. Although ORFV024
      interferes with activation of the NF-kappaB signaling pathway, its deletion from
      the OV-IA82 genome had no significant effect on disease severity, progression,
      and time to resolution in sheep, indicating that ORFV024 is not essential for
      virus virulence in the natural host. This represents the first description of a
      NF-kappaB inhibitor encoded by a parapoxvirus.

PMID- 20147407
TI  - Low pH-induced conformational change in herpes simplex virus glycoprotein B.
AB  - Herpesviruses can enter host cells using pH-dependent endocytosis pathways in a
      cell-specific manner. Envelope glycoprotein B (gB) is conserved among all
      herpesviruses and is a critical component of the complex that mediates membrane
      fusion and entry. Here we demonstrate that mildly acidic pH triggers specific
      conformational changes in herpes simplex virus (HSV) gB. The antigenic structure
      of gB was specifically altered by exposure to low pH both in vitro and during
      entry into host cells. The oligomeric conformation of gB was altered at a similar
      pH range. Exposure to acid pH appeared to convert virion gB into a lower-order
      oligomer. The detected conformational changes were reversible, similar to those
      in other class III fusion proteins. Exposure of purified, recombinant gB to
      mildly acidic pH resulted in similar changes in conformation and caused gB to
      become more hydrophobic, suggesting that low pH directly affects gB. We propose
      that intracellular low pH induces alterations in gB conformation that, together
      with additional triggers such as receptor binding, are essential for virion-cell
      fusion during herpesviral entry by endocytosis.

PMID- 20147408
TI  - The Elk-1 and serum response factor binding sites in the major immediate-early
      promoter of human cytomegalovirus are required for efficient viral replication in
      quiescent cells and compensate for inactivation of the NF-kappaB sites in
      proliferating cells.
AB  - The major immediate-early promoter (MIEP) region of human cytomegalovirus (HCMV)
      plays a critical role in the regulation of lytic and latent infections by
      integrating multiple signals supplied by the infecting virus, the type and
      physiological state of the host cell, and its extracellular surroundings. The
      interaction of cellular transcription factors with their cognate binding sites,
      which are present at high densities within the enhancer upstream from the MIEP
      core promoter, regulate the rate of IE gene transcription and thus affect the
      outcome of HCMV infection. We have shown previously that the NF-kappaB binding
      sites within the MIEP enhancer and cellular NF-kappaB activity induced by HCMV
      infection are required for efficient MIEP activity and viral replication in
      quiescent cells (P. Caposio, A. Luganini, G. Hahn, S. Landolfo, and G. Gribaudo,
      Cell. Microbiol. 9:2040-2054, 2007). We now show that the inactivation of either
      the Elk-1 or serum response factor (SRF) binding site within the enhancer also
      reduces MIEP activation and viral replication of recombinant HCMV viruses in
      quiescent fibroblasts. In these cells, we show that the expression of either Elk
      1 or SRF is required for optimal IE gene expression, and that the HCMV-stimulated
      activation of the MEK1/2-ERK1/2 signaling axis leads to Elk-1 transcriptional
      competency. Furthermore, the replication kinetics of recombinant viruses in which
      NF-kappaB, Elk-1, and SRF binding sites all are inactivated demonstrate that the
      higher levels of Elk-1 and SRF binding to MIEP in proliferating cells can
      compensate even for a lack of HCMV-induced NF-kappaB-mediated MIEP
      transactivation. These observations highlight the importance of the combination
      of different MIEP binding sites to optimize IE gene expression in cells in
      different physiological states.

PMID- 20147409
TI  - Relocalization of upstream binding factor to viral replication compartments is
      UL24 independent and follows the onset of herpes simplex virus 1 DNA synthesis.
AB  - Herpes simplex virus 1 (HSV-1) induces relocalization of several nucleolar
      proteins. We have found that, as for fibrillarin, the HSV-1-induced
      redistribution of two RNA polymerase I components, upstream binding factor (UBF)
      and RPA194, was independent of the viral protein UL24, which affects nucleolin
      localization. Nevertheless, the kinetics and sites of redistribution for
      fibrillarin and UBF differed. Interestingly, UBF remained associated with RPA194
      during infection. Although UBF is redistributed to viral replication compartments
      during infection, we did not detect foci of UBF at early sites of viral DNA
      synthesis, suggesting that it may not be directly involved in this process at
      early times.

PMID- 20147410
TI  - NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin
      type 1 of influenza virus.
AB  - Natural killer (NK) cells serve as a crucial first-line defense against tumors
      and virus-infected cells. We previously showed that lysis of influenza virus (IV)
      infected cells is mediated by the interaction between the NK receptor, NKp46, and
      the IV hemagglutinin (HA) type 1 expressed by the infected cells. This
      interaction requires the presence of sialyl groups on the NKp46-T225 O
      glycoforms. In the current study, we analyzed the O-glycan sequences that are
      imperative for the interaction between recombinant NKp46 (rNKp46) and IV H1N1
      strains. We first showed that rNKp46 binding to IV H1N1 is not mediated by a
      glycoform unique to the Thr225 site. We then characterized the O-glycan sequences
      that mediate the interaction of rNKp46 and IV H1N1; we employed rNKp46s with
      dissimilar glycosylation patterns and IV H1N1 strains with different sialic acid
      alpha2,3 and alpha2,6 linkage preferences. The branched alpha2,3-sialylated O
      glycoform Neu5NAcalpha2,3-Galbeta1,4-GlcNAcbeta1,6[Neu5NAcalpha2,3
      Galbeta1,3]GalNAc competently mediated the interaction of rNKp46 with IV H1N1,
      manifesting a preference for alpha2,3 linkage. In contrast, the linear alpha2,3
      sialylated O-glycoform Neu5NAcalpha2,3-Galbeta1,3-GalNAc was not correlated with
      enhanced interaction between rNKp46 and IV H1N1 or a preference for alpha2,3
      linkage. The branched alpha2,3- and alpha2,6-sialylated O-glycoform
      Neu5NAcalpha2,3-Galbeta1,3[Neu5NAcalpha2,6]GalNAc competently mediated the
      interaction of rNKp46 with IV H1N1, manifesting a preference for alpha2,6
      linkage. Previous viral HA-binding-specificity studies were performed with
      glycopolymer conjugates, free synthetic sialyl oligosaccharides, and sialidase
      treated cells. This study shed light on the O-glycan sequences involved in the
      interaction of glycoprotein and viral hemagglutinins and may help in the design
      of agents inhibitory to hemagglutinin for influenza treatment.

PMID- 20147411
TI  - Proviruses selected for high and stable expression of transduced genes accumulate
      in broadly transcribed genome areas.
AB  - Retroviruses and retrovirus-derived vectors integrate nonrandomly into the
      genomes of host cells with specific preferences for transcribed genes, gene-rich
      regions, and CpG islands. However, the genomic features that influence the
      transcriptional activities of integrated retroviruses or retroviral vectors are
      poorly understood. We report here the cloning and characterization of avian
      sarcoma virus integration sites from chicken tumors. Growing progressively,
      dependent on high and stable expression of the transduced v-src oncogene, these
      tumors represent clonal expansions of cells bearing transcriptionally active
      replication-defective proviruses. Therefore, integration sites in our study
      distinguished genomic loci favorable for the expression of integrated
      retroviruses and gene transfer vectors. Analysis of integration sites from avian
      sarcoma virus-induced tumors showed strikingly nonrandom distribution, with
      proviruses found prevalently within or close to transcription units, particularly
      in genes broadly expressed in multiple tissues but not in tissue-specifically
      expressed genes. We infer that proviruses integrated in these genomic areas
      efficiently avoid transcriptional silencing and remain active for a long time
      during the growth of tumors. Defining the differences between unselected
      retroviral integration sites and sites selected for long-terminal-repeat-driven
      gene expression is relevant for retrovirus-mediated gene transfer and has
      ramifications for gene therapy.

PMID- 20147412
TI  - Hepatitis B virus replication induces methylation of both host and viral DNA.
AB  - Control of viral replication is a major therapeutic goal to reduce morbidity and
      mortality from chronic hepatitis B virus (HBV) infection. Recently, methylation
      has been identified as a novel host defense mechanism, and methylation of viral
      DNA leads to downregulation of HBV gene expression. To better understand the
      mechanisms of HBV methylation, cell lines were exposed to HBV using a model
      system that mimics natural infection and the expression of host DNA
      methyltransferase genes (DNMTs) was measured. DNMT1, DNMT2, and DNMT3 were all
      significantly upregulated in response to HBV. DNMT3 was further studied because
      of its known role in the de novo methylation of DNA. Cotransfection experiments
      with full-length HBV and DNMT3 led to the downregulation of viral protein and
      pregenomic RNA production. To investigate whether the upregulation of DNMTs could
      also have an effect on the methylation of host DNA, cell lines were exposed to
      HBV in two independent model systems, one that mimics natural infection and a
      second model with temporary transfection. Host DNA methylation was measured by
      DNA microarray analysis. Increased methylation of host CpG islands was detected
      in both experimental systems. Two CpG islands, corresponding to genes SUFU and
      TIRAP, were selected, and the downregulation of these genes in hepatocellular
      carcinomas was confirmed. In conclusion, hepatocytes respond to HBV infection by
      upregulating DNMTs. The DNMTs methylate viral DNA, leading to decreased viral
      gene expression and decreased viral replication. However, virus-induced
      overexpression of DNMTs also leads to methylation of host CpG islands.

PMID- 20147413
TI  - Influence of bilateral vestibular loss on spinal stabilization in humans.
AB  - The control of upper body (UB) orientation relative to the pelvis in the frontal
      plane was characterized in bilateral vestibular loss subjects (BVLs) and compared
      with healthy control subjects (Cs). UB responses to external perturbations were
      evoked using continuous pelvis tilts (eyes open and eyes closed) at various
      amplitudes. Lateral sway of the lower body was prevented on all tests. UB sway
      was summarized using root-mean-square measures and dynamic behavior was
      characterized using frequency response functions (FRFs) from 0.023 to 10.3 Hz.
      Both subject groups had similar FRF variations as a function of stimulus
      frequency and were relatively unaffected by visual availability, indicating that
      visual orientation cues contributed very little to UB control. BVLs had larger UB
      sway at frequencies below ~1 Hz compared with Cs. A feedback model of UB
      orientation control was used to identify sensory contributions to spinal
      stability and differences between subject groups. The model-based interpretation
      of experimental results indicated that a phasic proprioceptive signal encoding
      the angular velocity of UB relative to lower body motion was a major contributor
      to overall system damping. Parametric system identification showed that BVLs used
      proprioceptive information that oriented the UB toward the pelvis to a greater
      extent compared with Cs. Both subject groups used sensory information that
      oriented the UB vertical in space to a greater extent as pelvis tilt amplitudes
      increased. In BVLs, proprioceptive information signaling the UB orientation
      relative to the fixed lower body provided the vertical reference, whereas in Cs,
      vestibular information also contributed to the vertical reference.

PMID- 20147414
TI  - Effect of salicylate on KCNQ4 of the guinea pig outer hair cell.
AB  - Salicylate causes a moderate hearing loss and tinnitus in humans at high-dose
      levels. Salicylate-induced hearing loss has been attributed to impaired sound
      amplification by outer hair cells (OHCs) through its direct action on the OHC
      motility sensor and/or motor. However, there is a disparity of salicylate
      concentrations between the clinical and animal studies, i.e., extremely high
      extracellular concentrations of salicylate (from 1 to 10 mM) is required to
      produce a significant reduction of electromotility in animal studies. Such
      concentrations are above the clinical/physiological range for humans. Here, we
      showed that clinical/physiological concentration range of salicylate caused
      concentration-dependent and reversible reductions in I(K,n) (KCNQ4) and
      subsequent depolarization of OHCs. Salicylate reduced the maximal tail current of
      the activation curve of I(K,n) without altering the voltage-sensitivity
      (V(half)). The salicylate-induced reduction of I(K,n) was almost completely
      blocked by linopirdine (0.1 mM) and BaCl2 (10 mM). Consistent with the finding in
      OHCs, salicylate significantly reduced KCNQ4-mediated current expressed in
      Chinese hamster ovarian (CHO) cells by comparable amplitude to OHCs without
      significantly shifting V(half). Nonstationary fluctuation analysis shows that
      salicylate significantly reduced the estimated single-channel current amplitude
      and numbers. Intracellular Ca2+ elevation resulting from cytoplasmic acidosis
      also contributes to the current reduction of I(K,n) (KCNQ4) of OHCs. These
      results indicate a different model for the salicylate-induced hearing loss
      through the reduction of KCNQ4 and subsequent depolarization of OHCs, which
      reduces the driving force for transduction current and electromotility. The major
      mechanism underlying the reduction of I(K,n) (KCNQ4) is the direct blocking
      action of salicylate on KCNQ4.

PMID- 20147415
TI  - Contralateral delay activity provides a neural measure of the number of
      representations in visual working memory.
AB  - Visual working memory (VWM) helps to temporarily represent information from the
      visual environment and is severely limited in capacity. Recent work has linked
      various forms of neural activity to the ongoing representations in VWM. One piece
      of evidence comes from human event-related potential studies, which find a
      sustained contralateral negativity during the retention period of VWM tasks. This
      contralateral delay activity (CDA) has previously been shown to increase in
      amplitude as the number of memory items increases, up to the individual's working
      memory capacity limit. However, significant alternative hypotheses remain
      regarding the true nature of this activity. Here we test whether the CDA is
      modulated by the perceptual requirements of the memory items as well as whether
      it is determined by the number of locations that are being attended within the
      display. Our results provide evidence against these two alternative accounts and
      instead strongly support the interpretation that this activity reflects the
      current number of objects that are being represented in VWM.

PMID- 20147416
TI  - Major differences in the proportion of amino acid fiber types transmitting taste
      information from oral and extraoral regions in the channel catfish.
AB  - The present study investigates for the first time in any teleost the amino acid
      specificity and sensitivity of single glossopharyngeal (cranial nerve IX) fibers
      that innervate taste buds within the oropharyngeal cavity. These results are
      contrasted with similar data obtained from facial (cranial nerve VII) fibers that
      innervate extraoral taste buds. The major finding is that functional differences
      are clearly evident between taste fibers of these two cranial nerves. Catfish
      possess the most extensive distribution of taste buds found in vertebrates. Taste
      buds on the external body surface are exclusively innervated by VII, whereas IX,
      along with the vagus (X), innervate the vast majority of taste buds within the
      oropharyngeal cavity. Responses to the l-isomers of alanine (Ala), arginine
      (Arg), and proline (Pro), the three most stimulatory amino acids that bind to
      independent taste receptors, were obtained from 90 single VII and 64 single IX
      taste fibers. This study confirmed a previous investigation that the amino acid
      responsive VII fibers consist of two major groups, the Ala and Arg clusters
      containing taste fibers having thresholds in the etaM range. In contrast, the
      present study indicates the amino acid responsive IX taste system is dominated by
      taste fibers responsive to Pro and to Pro and Arg, respectively, has a reduced
      percentage of Ala fibers, and is less sensitive than VII. The present
      electrophysiological results are consistent with previous experiments, indicating
      that the extraoral taste system is essential for appetitive behavior, whereas
      oropharyngeal taste buds are critical for consummatory behavior.

PMID- 20147417
TI  - Thinking about walking: effects of conscious correction versus distraction on
      locomotor adaptation.
AB  - Control of the human walking pattern normally requires little thought, with
      conscious control used only in the face of a challenging environment or a
      perturbation. We have previously shown that people can adapt spatial and temporal
      aspects of walking to a sustained perturbation generated by a split-belt
      treadmill. Here we tested whether conscious correction of walking, versus
      distraction from it, modifies adaptation. Conscious correction of stepping may
      expedite the adaptive process and help to form a new walking pattern. However,
      because walking is normally an automatic process, it is possible that conscious
      effort could interfere with adaptation, whereas distraction might improve it by
      removing competing voluntary control. Three groups of subjects were studied: a
      control group was given no specific instructions, a conscious correction group
      was instructed how to step and given intermittent visual feedback of stepping
      during adaptation, and a distraction group performed a dual-task during
      adaptation. After adaptation, retention of aftereffects was assessed in all
      groups during normal treadmill walking without conscious effort, feedback, or
      distraction. We found that conscious correction speeds adaptation, whereas
      distraction slows it. Subjects trained with distraction retained aftereffects
      longest, suggesting that the training used during adaptation predicts the time
      course of deadaptation. An unexpected finding was that these manipulations
      affected the adaptation rate of spatial but not temporal elements of walking.
      Thus conscious processes can preferentially access the spatial walking pattern.
      It may be that spatial and temporal controls of locomotion are accessible through
      distinct neural circuits, with the former being most sensitive to conscious
      effort or distraction.

PMID- 20147418
TI  - Responses in the inferior colliculus of the guinea pig to concurrent harmonic
      series and the effect of inactivation of descending controls.
AB  - One of the fundamental questions of auditory research is how sounds are
      segregated because, in natural environments, multiple sounds tend to occur at the
      same time. Concurrent sounds, such as two talkers, physically add together and
      arrive at the ear as a single input sound wave. The auditory system easily
      segregates this input into a coherent perception of each of the multiple sources.
      A common feature of speech and communication calls is their harmonic structure
      and in this report we used two harmonic complexes to study the role of the
      corticofugal pathway in the processing of concurrent sounds. We demonstrate that,
      in the inferior colliculus (IC) of the anesthetized guinea pig, deactivation of
      the auditory cortex altered the temporal and/or the spike response to the
      concurrent, monaural harmonic complexes. More specifically, deactivating the
      auditory cortex altered the representation of the relative level of the
      complexes. This suggests that the auditory cortex modulates the representation of
      the level of two harmonic complexes in the IC. Since sound level is a cue used in
      the segregation of auditory input, the corticofugal pathway may play a role in
      this segregation.

PMID- 20147420
TI  - An investigation into the length of hospital stay for deaf mental health service
      users.
AB  - This study looked at the average length of hospital stay for inpatients in a
      specialist deaf mental health service over a 10-year period, in comparison to
      that of a general psychiatric hearing cohort. In addition, two case studies of
      deaf inpatients were carried out looking specifically at the prerequisite factors
      governing discharge. Finally, a comparison of the types of community-based
      services available to deaf and hearing service users was undertaken in order to
      establish whether there was now a similarity of provision for both groups. The
      conclusion reached was that deaf inpatients are likely to remain in hospital
      twice as long as their hearing peers, but explanations for this difference may
      not necessarily be solely of a clinical nature. There is some evidence to suggest
      that social factors (i.e., a lack of appropriate community support,
      rehabilitation services, and provision) may have a negative impact on length of
      hospital stay. It is suggested that an increase in community-based services and
      provision may well shorten the length of hospital stay for deaf service users in
      the future. It is also recommended that further research into the relative
      effects of clinical versus social factors is considered.

PMID- 20147419
TI  - Neural coding of periodicity in marmoset auditory cortex.
AB  - Pitch, our perception of how high or low a sound is on a musical scale, crucially
      depends on a sound's periodicity. If an acoustic signal is temporally jittered so
      that it becomes aperiodic, the pitch will no longer be perceivable even though
      other acoustical features that normally covary with pitch are unchanged. Previous
      electrophysiological studies investigating pitch have typically used only
      periodic acoustic stimuli, and as such these studies cannot distinguish between a
      neural representation of pitch and an acoustical feature that only correlates
      with pitch. In this report, we examine in the auditory cortex of awake marmoset
      monkeys (Callithrix jacchus) the neural coding of a periodicity's repetition
      rate, an acoustic feature that covaries with pitch. We first examine if
      individual neurons show similar repetition rate tuning for different periodic
      acoustic signals. We next measure how sensitive these neural representations are
      to the temporal regularity of the acoustic signal. We find that neurons
      throughout auditory cortex covary their firing rate with the repetition rate of
      an acoustic signal. However, similar repetition rate tuning across acoustic
      stimuli and sensitivity to temporal regularity were generally only observed in a
      small group of neurons found near the anterolateral border of primary auditory
      cortex, the location of a previously identified putative pitch processing center.
      These results suggest that although the encoding of repetition rate is a general
      component of auditory cortical processing, the neural correlate of periodicity is
      confined to a special class of pitch-selective neurons within the putative pitch
      processing center of auditory cortex.

PMID- 20147421
TI  - Science and evidence of success: two emerging issues in assessment accommodations
      for students who are deaf or hard of hearing.
AB  - In the United States, students who are deaf or hard of hearing (SDHH) are
      required to participate in high-stakes standardized assessments under No Child
      Left Behind reforms. In 2006-2007, states added science to reading and
      mathematics as a tested content area. Many SDHH participate in these assessments
      using testing accommodations, but teachers have few evidence-based resources to
      draw upon when making accommodations decisions. Two research questions guided
      this study: (a) What were patterns of SDHH 2006-2007 test accommodations use in
      state standardized assessments in mathematics, reading, and science? (b) What
      evidence did teachers use to determine the effectiveness of accommodations for
      SDHH? A total of 290 participants described their assessment practices with SDHH
      via an online and paper-and-pencil survey. Extended time, small group, and test
      directions interpreted were the most frequently used accommodations by SDHH, but
      there were some different patterns in science for accommodations that included
      changes to the test items. Teachers reported both student satisfaction and test
      score validity epistemologies of accommodations' effectiveness.

PMID- 20147422
TI  - Local decision-makers views' of national guidance on interventional procedures in
      the UK.
AB  - OBJECTIVES: To identify how decision-makers in the NHS perceive and manage
      interventional procedures guidance and to determine whether additional
      information would be useful. METHODS: Qualitative study using semi-structured
      interviews with seven providers, six commissioners and one policy-maker. The
      framework approach was used to analyse transcribed data, and emergent themes
      coded. Data were analysed separately for providers and commissioner
      organizations. RESULTS: Perceptions about how guidance is managed in provider
      organizations varied. Some decision-makers considered that guidance is handled
      very well whereas others think it is suboptimal and haphazard. It is unclear
      whether clinicians follow procedure for cautionary guidance. In commissioner
      organizations, guidance is not seen as a priority by most and is not considered
      an area that will soon enter routine clinical practice. Moreover, commissioners
      felt that guidance lacked relevance as there is no consideration of whether
      procedures are cost-effective or affordable. Despite this, respondents perceived
      that the content and quality of guidance is satisfactory. Useful additional
      information for inclusion in guidance would be: prevalence, incidence, cost,
      patients' views, consequences of using the new intervention, comparative
      information, effectiveness and cost-effectiveness. CONCLUSIONS: Management of
      interventional procedures guidance in the NHS can be improved. It is important to
      understand the ways in which guidance meets and fails to meet decision-makers'
      needs.

PMID- 20147423
TI  - Patients' and staffs' experiences of an automated telephone weather forecasting
      service.
AB  - OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) have
      recently been offered severe weather warnings and medication reminders using an
      automated telephone service and interactive voice recognition technology. Our aim
      was to explore patients' and health care staffs' perceptions and experiences of
      the technologies, their contribution to the management of COPD and implementation
      issues. METHODS: Qualitative semi-structured telephone interviews were undertaken
      with 18 patients and six staff from five primary care centres in the Bradford
      area, England. Interview transcripts were thematically analysed. RESULTS:
      Patients considered the telephone service was an appropriate way to deliver
      information but there was some variation in perceived usefulness. Many patients
      praised the service, valuing reassurance and medication reminders, but others
      were indifferent and even critical. Criticism tended to reflect scepticism over
      the reliability of weather forecasts information rather than the automated
      telephone service itself. There was limited impact on the management strategies
      of patients apart from some patients ordering medication. Primary care staff
      considered the service a success but some felt that it lacked participation by
      hard-to-reach groups (non-English speaking, mild COPD patients). Our concerns
      about the resource implications of successful implementation were also raised.
      CONCLUSIONS: An automated telephone service was generally acceptable to patients
      but changes in COPD management were limited, possibly because the patients
      already had a good understanding of their condition and self-management
      strategies. Implications for practice include the need for strategies to target
      hard-to-reach groups which may need more resources.

PMID- 20147424
TI  - Impact of clinician judgement on formulary committees' recommendations in Canada.
AB  - OBJECTIVES: In formulary committee deliberations, evidence for the efficacy of
      medications is often based on changes in the scale scores of patient-reported
      outcome measures. Our aim was to examine whether clinician judgement about the
      efficacy of medications for Alzheimer's disease, when added to scale score
      evidence, affects formulary committee members' recommendations about providing
      these medications under public insurance. METHODS: The study was conducted using
      mixed methods. In a survey of formulary committee members in Canada, 32
      participants were presented with scenarios that outlined different levels of
      efficacy for a medication. For each scenario, participants were asked to specify
      their likelihood of recommending that the medication be provided under public
      insurance. Of the 32 participants, 23 agreed to take part in an interview to
      explain the survey results. Content analysis was used to elicit recurrent themes
      across the interviews. RESULTS: When a medication was disease modifying, use of
      clinician judgement increased the mean likelihood of recommending that the
      medication be provided under public insurance. Despite this, some participants
      felt formulary committees should not use clinician judgement because of risks of
      subjectivity and bias. However, other participants believed the addition of
      clinician judgement would enhance the clinical relevance of evidence that might
      otherwise be based entirely on changes in scale score. CONCLUSIONS: Clinician
      judgement about the efficacy of medications can influence formulary committee
      recommendations. This suggests the need for a new approach to govern the
      consideration of expert evidence during formulary committee deliberations.

PMID- 20147425
TI  - Response to 'The appropriation of complexity theory in health care'.

PMID- 20147426
TI  - HIV testing of health care workers in England--a flawed policy.
AB  - A new Department of Health policy in England, published in 2007, recommended
      changes to the pre-employment health checks performed on health care workers
      before taking up their employment. The policy proposed that all new health care
      workers should receive immunization against TB and hepatitis B and should be
      offered testing for hepatitis C and HIV. It also advanced a new requirement that
      staff who perform exposure-prone procedures must be tested for TB, hepatitis B
      and C and HIV and must test negative for these diseases. Essentially mandatory
      HIV testing has been introduced for a large number of health care workers. The
      aim of the recommendations is to protect patients from contracting serious
      communicable diseases from health care professionals. Secondary objectives of the
      directive are to maintain confidence in the workforce and reduce the burden of
      patient notification exercises. This essay explores some of the shortcomings of
      this policy and examines the reasons why this policy will fail to meet its
      objectives. The justification for this new guidance is questioned and some of the
      ethical issues are highlighted.

PMID- 20147427
TI  - Cost and impact of a quality improvement programme in mental health services.
AB  - OBJECTIVE: To estimate the cost and impact of a centrally-driven quality
      improvement initiative in four UK mental health communities. METHODS: Total costs
      in year 1 were identified using documentation, a staff survey, semi-structured
      interviews and discussion groups. Few outcome data were collected within the
      programme so thematic analysis was used to identify the programme's impact within
      its five broad underlying principles. RESULTS: The survey had a 40% response.
      Total costs ranged between pound164,000 and pound458,000 per site, plus staff
      time spent on workstreams. There was a very hazy view of the resources absorbed
      and poor recording of expenditure and activity. The initiative generated little
      demonstrable improvements in service quality but some participants reported
      changes in attitudes. CONCLUSIONS: Given the difficult contexts, short time
      scales and capacity constraints, the programme's lack of impact is not
      surprising. It may, however, represent a worthwhile investment in cultural change
      which might facilitate improvements in how services are delivered.

PMID- 20147428
TI  - Accountability of foundation trusts in the English NHS: views of directors and
      governors.
AB  - OBJECTIVES: To map and describe the formal accountability relationships of
      foundation trusts in England and to explore the interpretations of these
      relationships by the key actors. METHODS: Documentary analysis and interviews
      with chief executives, chairs, directors and governors in six acute trusts and
      two Strategic Health Authorities. RESULTS: Although vertical accountability to
      the Department of Health (via Strategic Health Authorities) has, in formal terms,
      been removed some foundation trusts continue to be held to accountability by
      Strategic Health Authorities, albeit informally. Directors of foundation trusts
      perceive strong accountable to their regulator, Monitor, particularly for
      financial performance, but there is some confusion about where accountability for
      quality of care rests. Horizontal lines of accountability to the local population
      (through Local Involvement Networks and local government Overview and Scrutiny
      Committees) remain weak. CONCLUSIONS: Contrary to the major policy objectives of
      giving greater autonomy to foundation trusts and making them more accountable to
      the local population, they continue to look towards the Department of Health
      rather than to the local population and its representatives. The accountability
      of foundation trusts needs to be simplified, clarified and strengthened.

PMID- 20147430
TI  - Patient safety first?

PMID- 20147429
TI  - Psychosocial mediators of a faith-based physical activity intervention:
      implications and lessons learned from null findings.
AB  - Mediation analyses in faith-based physical activity (PA) interventions targeting
      African-American adults are lacking. The purpose of this study was to examine the
      psychosocial mediators of a faith-based PA intervention with African-American
      adults. Churches were randomly assigned to receive immediate or delayed (1-year
      later) training in PA program implementation. A subsample of participants from
      randomly selected churches took part in telephone surveys at baseline and at 1
      year. The primary outcome was percentage of participants meeting PA
      recommendations. MacKinnon's product of coefficients was used to test for
      mediation. Participants (n = 418) from 20 churches completed the baseline and 1
      year follow-up surveys. There were no statistically significant changes in PA
      behavior at 1 year. The intervention had a marginally significant effect on
      increasing the amount of instrumental church support received by church members.
      However, none of the psychosocial variables tested were found to be significant
      mediators of the intervention. Mediation analyses provided insight into potential
      reasons as to why the Health-e-AME intervention did not change PA. The
      intervention did not successfully change the targeted mediators hypothesized to
      change PA. Potential reasons for these shortcomings as well as issues to address
      in future faith-based studies are discussed.

PMID- 20147431
TI  - Management of community-associated MRSA.
AB  - Around a quarter of healthy people are asymptomatic carriers of Staphylococcus
      aureus, which colonises the skin and nasopharynx. However, this organism is also
      the major bacterial cause of skin, soft tissue and bone infections, and
      healthcare-associated bacteraemia,1 with problems ranging from superficial skin
      conditions to severe, sometimes fatal, systemic disease. Serious S. aureus
      infections can be caused by strains of the organism that are meticillin
      susceptible (MSSA) or meticillin-resistant (MRSA). 'Healthcare-associated' MRSA
      (HA-MRSA) emerged in the 1960s as a cause of infection in hospital or other
      healthcare settings, or in the community after hospital discharge. More recently,
      'community-associated' MRSA (CA-MRSA) has been described; patients infected with
      this type of organism typically have no history of hospitalisation or residence
      in long-term care. CA-MRSA infection is important because it can cause life
      threatening illnesses (e.g. haemorrhagic necrotising pneumonia). Here we discuss
      the management of patients with such infection.

PMID- 20147432
TI  - Pregabalin for generalised anxiety disorder.
AB  - Generalised anxiety disorder (GAD) is common, with a prevalence of around 4%
      among adults in the UK. The condition is characterised by chronic excessive
      anxiety and worry, in combination with a variety of psychological or somatic
      symptoms. It can be very distressing and disabling and, if left untreated, can be
      costly to both the individual and society. Pregabalin (Lyrica - Pfizer) is a
      medicine licensed for GAD in adults. Here we review its role in the management of
      patients with the problem.

PMID- 20147433
TI  - A change of units for HbA(1c).
AB  - Worldwide, measurement of glycated haemoglobin (HbA(1c)) is the mainstay for
      monitoring long-term glycaemic control in people with diabetes mellitus. However,
      until recently there was no internationally agreed standard for measuring and
      reporting HbA(1c) levels. There is now an international standard for HbA(1c),
      agreed by the International Federation of Clinical Chemistry (IFCC), and from 1
      June 2009 all UK laboratories began reporting HbA(1c) in the new units according
      to this standard. Here we explain the rationale behind this change.

PMID- 20147434
TI  - Mortality and cancer incidence in a nickel cohort.
AB  - BACKGROUND: Previous studies of nickel workers have primarily noted significant
      early increases in lung and nasal cancers and for various types of accidents.
      AIMS: To examine cancer incidence and mortality, concurrently, for a cohort of
      male nickel workers at a major nickel and copper producer in Sudbury, Ontario,
      Canada. METHODS: From January 1964 to December 2001, nominal roll and work
      history information were linked to Ontario health data and mortality and cancer
      incidence were compared to the Ontario population. RESULTS: There were 1984 (19%)
      deaths and 1127 (11%) incident cancers (n = 10,253). Significant elevations in
      mortality were observed for accidents, poisoning and violence; for possibly job
      related accidents among those with <15 years since first hire [standardized
      mortality ratio (SMR) = 133, 95% CI: 111-158; SMR = 241, 95% CI: 159-351,
      respectively] and for accidents in those with > or =15 years since first hire
      (SMR = 123, 95% CI: 104-144). Significant elevations were also observed for
      accidents, poisoning and violence for those with 6 months to 14 years work
      experience and for lung cancer incidence and mortality for those with 15-29 years
      work experience (SMR = 128, 95% CI: 107-153). Incident lung cancers were
      significantly elevated for those hired in the 1940s and 1960s. CONCLUSIONS:
      Significant lung cancer mortality and incidence elevations were observed for the
      cohort and underground workers with increased time since first hire, for those
      hired during early periods of operation and for those with longer durations of
      employment. Further aetiological study is required as occupational aetiology
      could not be ascertained.

PMID- 20147435
TI  - Psychometric properties of the FACES-IV in a pediatric oncology population.
AB  - OBJECTIVE: The purpose of this study was to examine the psychometric properties
      of the Family Adaptability and Cohesion Evaluation Scales, version IV (FACES-IV)
      in families of children with cancer. METHODS: As part of a larger program of
      research, 147 mothers and 40 fathers from 162 families of children with cancer
      completed the FACES-IV. Parents and one healthy child from each family (77 girls;
      age M = 12.8, SD = 2.8) completed additional measures of family functioning and
      parenting. RESULTS: Internal consistencies above .70 were found for all subscales
      except one (Enmeshed, alpha = .65). Intercorrelations of the subscales were
      similar to the validation sample but seemed inconsistent with the Circumplex
      Model on which the measure is based. Analyses raised questions regarding
      construct validity for the Enmeshed and Rigid subscales. CONCLUSIONS: These
      preliminary findings suggest that more research is needed prior to widespread use
      of the FACES-IV in pediatric oncology populations.

PMID- 20147436
TI  - Internal and external paralogy in the evolution of tropomyosin genes in
      metazoans.
AB  - Nature contains a tremendous diversity of forms both at the organismal and
      genomic levels. This diversity motivates the twin central questions of molecular
      evolution: what are the molecular mechanisms of adaptation, and what are the
      functional consequences of genomic diversity. We report a 22-species comparative
      analysis of tropomyosin (PPM) genes, which exist in a variety of forms and are
      implicated in the emergence of a wealth of cellular functions, including the
      novel muscle functions integral to the functional diversification of bilateral
      animals. TPM genes encode either or both of long-form [284 amino acid (aa)] and
      short-form (approximately 248 aa) proteins. Consistent with a role of TPM
      diversification in the origins and radiation of bilaterians, we find evidence
      that the muscle-specific long-form protein arose in proximal bilaterian ancestors
      (the bilaterian 'stem'). Duplication of the 5' end of the gene led to alternative
      promoters encoding long- and short-form transcripts with distinct functions. This
      dual-function gene then underwent strikingly parallel evolution in different
      bilaterian lineages. In each case, recurrent tandem exon duplication and mutually
      exclusive alternative splicing of the duplicates, with further association
      between these alternatively spliced exons along the gene, led to long- and short
      form-specific exons, allowing for gradual emergence of alternative "internal
      paralogs" within the same gene. We term these Mutually exclusively Alternatively
      spliced Tandemly duplicated Exon sets "MATEs". This emergence of internal
      paralogs in various bilaterians has employed every single TPM exon in at least
      one lineage and reaches striking levels of divergence with up to 77% of long- and
      short-form transcripts being transcribed from different genomic regions.
      Interestingly, in some lineages, these internal alternatively spliced paralogs
      have subsequently been "externalized" by full gene duplication and reciprocal
      retention/loss of the two transcript isoforms, a particularly clear case of
      evolution by subfunctionalization. This parallel evolution of TPM genes in
      diverse metazoans attests to common selective forces driving divergence of
      different gene transcripts and represents a striking case of emergence of
      evolutionary novelty by alternative splicing.

PMID- 20147437
TI  - Translocation of Y-linked genes to the dot chromosome in Drosophila
      pseudoobscura.
AB  - One of the most striking cases of sex chromosome reorganization in Drosophila
      occurred in the lineage ancestral to Drosophila pseudoobscura, where there was a
      translocation of Y-linked genes to an autosome. These genes went from being
      present only in males, never recombining, and having an effective population size
      of 0.5N to a state of autosomal linkage, where they are passed through both
      sexes, may recombine, and their effective population size has quadrupled. These
      genes appear to be functional, and they underwent a drastic reduction in intron
      size after the translocation. A Y-autosome translocation may pose problems in
      meiosis if the rDNA locus responsible for X-Y pairing had also moved to an
      autosome. In this study, we demonstrate that the Y-autosome translocation moved Y
      linked genes onto the dot chromosome, a small, mainly heterochromatic autosome
      with some sex chromosome-like properties. The rDNA repeats occur exclusively on
      the X chromosome in D. pseudoobscura, but we found that the new Y chromosome of
      this species harbors four clusters bearing only the intergenic spacer region
      (IGS) of the rDNA repeats. This arrangement appears analogous to the situation in
      Drosophila simulans, where X-rDNA to Y-IGS pairing could be responsible for X-Y
      chromosome pairing. We postulate that the nascent D. pseudoobscura Y chromosome
      acquired and amplified copies of the IGS, suggesting a potential mechanism for X
      Y pairing in D. pseudoobscura.

PMID- 20147438
TI  - Interactions among proteins of floral MADS-box genes in basal eudicots:
      implications for evolution of the regulatory network for flower development.
AB  - Floral MADS-box genes encode transcription factors that play critical roles in
      the development and evolution of the flower. Proteins of floral MADS-box genes
      regulate the expression of their downstream genes by forming various
      homodimers/heterodimers and quaternary complexes. Interactions among proteins of
      floral MADS-box genes have been documented in several model species, yet the
      information accumulated so far is still not sufficient to draw a general picture
      of the evolution of the interactions. We have characterized 28 putative floral
      MADS-box genes from three representative basal eudicots (i.e., Euptelea
      pleiospermum, Akebia trifoliata, and Pachysandra terminalis) and investigated the
      protein-protein interactions (PPIs) among the proteins encoded by these genes
      using yeast two-hybrid assays. We found that, although the PPIs in basal eudicots
      are largely consistent with those in core eudicots and monocots, there are
      lineage-specific features that have not been observed elsewhere. We also
      reconstructed the evolutionary histories of the PPIs among members of seven MADS
      box gene lineages (i.e., AP1, AP3, PI, AG, STK, AGL2, and AGL9) in angiosperms.
      We revealed that the PPIs were extremely conserved in nine (or 32.1%) of the 28
      possible combinations, whereas considerable variations existed in seven (25.0%)
      of them; in the remaining 12 (or 42.9%) combinations, however, no interaction was
      observed. Notably, most of the PPIs required for the formation of quaternary
      complexes, as suggested by the "quartet model," were highly conserved. This
      suggested that the evolutionarily conservative PPIs may have played critical
      roles in the establishment of the basic structure (or architecture) of the flower
      and experienced coevolution to maintain their functions. The evolutionarily
      variable PPIs, however, seem to have played subsidiary roles in flower
      development and have contributed to the variation in floral traits.

PMID- 20147439
TI  - Contribution of high basolateral bile salt efflux to the lack of hepatotoxicity
      in rat in response to drugs inducing cholestasis in human.
AB  - Intrahepatic bile acid accumulation due to inhibition of the bile salt export
      pump (BSEP) has been proposed as a mechanism for drug-induced cholestasis. Many
      cholestatic drugs do not initiate hepatotoxicity in rats, although they inhibit
      rat Bsep and cause elevated serum bile acid concentration. In this study, we
      examined changes in the taurocholate (TC) transport in response to cholestatic
      drug treatments in human and rat sandwich-cultured hepatocytes. Our experimental
      setup allows studying the basolateral and canalicular efflux simultaneously, thus
      comparing drug-induced changes in the vectorial efflux of TC. We found that TC
      elimination highly differs in human and rat hepatocytes. In human hepatocytes, an
      equal fraction of TC(uptake) was eliminated by basolateral (34.8%) and
      canalicular (34.4%) transporters and remained in the cells (30.5%), while in the
      case of rats, the basolateral transport was dominant (71.7%) and intracellular TC
      accumulation was negligible (6.9%). The inhibition of BSEP/Bsep resulted in
      significantly higher intracellular TC(conc) in humans than in rats. The 15-fold
      difference in intracellular TC(conc) of control in human versus rat hepatocytes
      was increased 25-fold by troglitazone treatment. MK571 and indomethacin decreased
      the basolateral efflux and significantly increased the intracellular TC(conc) in
      rats. In rat hepatocytes, the highest intracellular TC(conc) was observed with
      cyclosporine A and glibenclamide, which inhibited TC elimination in both
      directions. Nevertheless, the basolateral transport remained dominant. We
      conclude that in rats, the higher rate of basolateral bile salt efflux represents
      an additional protective mechanism in cholestasis, which contributes to species
      differences in response to hepatotoxic drugs.

PMID- 20147444
TI  - Is it time to end concerns over the estrogenic effects of bisphenol A?

PMID- 20147445
TI  - Primary Sjogren's syndrome: too dry and too tired.
AB  - Chronic fatigue is one of the most prevalent and debilitating symptoms in primary
      SS (pSS). Approximately 70% of pSS patients suffer from disabling fatigue, which
      is associated with reduced health-related quality of life. In this article, we
      review the instruments used for evaluating pSS-related fatigue, our current
      understanding of the underlying psychosocial and physiological mechanisms of
      fatigue in pSS and the therapeutic strategies that have been studied in the
      management of fatigue in pSS.

PMID- 20147446
TI  - Apoptosis in the rheumatoid arthritis synovial membrane: modulation by disease
      modifying anti-rheumatic drug treatment.
AB  - OBJECTIVES: RA is characterized at the synovial tissue level by synovial lining
      hyperplasia, angiogenesis and mononuclear cell infiltrates. A failure of
      apoptotic pathways may explain these pathological changes in RA synovial tissue.
      This study aims to demonstrate the presence of initiators and inhibitors of
      apoptosis in RA synovial tissue and the effect of treatment with DMARDs on
      apoptotic pathways in RA. METHODS: Synovial biopsy specimens were obtained at
      arthroscopy from 16 RA patients before and at 3- or 6-month intervals after
      commencing treatment with a DMARD. Apoptosis (by the terminal deoxynucleotidyl
      transferase mediated dUTP nick end labelling method and polyADP-ribose polymerase
      staining), proteins regulating apoptosis [Fas, FADD-like IL1b converting enzyme
      inhibitory protein (FLIP), Bcl-2, Survivin and X-linked inhibitor of apoptosis
      protein (XIAP)] and the presence of activated caspases (caspases 3 and 8) were
      detected by immunohistochemistry and quantified using image analysis and
      semiquantitative techniques. RESULTS: Fifteen patients responded to treatment,
      with an ACR response of > or =20%, 13 achieving an ACR response of > or =50% and
      3 achieving an ACR remission. There was a significant reduction in SM macrophages
      and memory T cells, with an increase in fibroblast-like synovial lining cells
      following DMARD treatment. Apoptosis was not detected in the inflamed synovial
      tissue of RA patients before starting treatment, despite evidence of caspase
      activation, but was detectable after successful treatment with DMARDs. Inhibitors
      of activated caspases (FLIP, Survivin and XIAP) were detected in RA synovial
      tissue and were down-modulated with successful DMARD treatment. CONCLUSIONS:
      Apoptotic pathways are defective in RA synovial tissue from patients with active
      disease, despite the presence of activated caspases, possibly due to the abundant
      expression of inhibitors of the caspase pathway in RA synovial tissue. DMARD
      treatment can modulate apoptosis in the RA SM, which may lead to restoration of
      the SM architecture towards that of normal synovial tissue.

PMID- 20147447
TI  - Growth factor erv1-like modulates Drp1 to preserve mitochondrial dynamics and
      function in mouse embryonic stem cells.
AB  - The relationship of mitochondrial dynamics and function to pluripotency are
      rather poorly understood aspects of stem cell biology. Here we show that growth
      factor erv1-like (Gfer) is involved in preserving mouse embryonic stem cell (ESC)
      mitochondrial morphology and function. Knockdown (KD) of Gfer in ESCs leads to
      decreased pluripotency marker expression, embryoid body (EB) formation, cell
      survival, and loss of mitochondrial function. Mitochondria in Gfer-KD ESCs
      undergo excessive fragmentation and mitophagy, whereas those in ESCs
      overexpressing Gfer appear elongated. Levels of the mitochondrial fission GTPase
      dynamin-related protein 1 (Drp1) are highly elevated in Gfer-KD ESCs and
      decreased in Gfer-overexpressing cells. Treatment with a specific inhibitor of
      Drp1 rescues mitochondrial function and apoptosis, whereas expression of Drp1
      dominant negative resulted in the restoration of pluripotency marker expression
      in Gfer-KD ESCs. Altogether, our data reveal a novel prosurvival role for Gfer in
      maintaining mitochondrial fission-fusion dynamics in pluripotent ESCs.

PMID- 20147448
TI  - The yeast formin Bnr1p has two localization regions that show spatially and
      temporally distinct association with septin structures.
AB  - Formins are conserved eukaryotic proteins that direct the nucleation and
      elongation of unbranched actin filaments. The yeast formins, Bni1p and Bnr1p,
      assemble actin cables from the bud cortex and bud neck, respectively, to guide
      overall cell polarity. Here we examine the regions of Bnr1p responsible for bud
      neck localization. We define two non-overlapping regions, Bnr1p-L1 (1-466) and
      Bnr1p-L2 (466-733), that can each localize to the bud neck independently of
      endogenous Bnr1p. Bnr1p-L1 and Bnr1p-L2 localize with septins at the bud neck,
      but show slightly differently spatial and temporal localization, reflecting the
      localization (Bnr1p-L1) or cell cycle timing (Bnr1p-L2) of full-length Bnr1p.
      Bnr1p is known to be very stably localized at the bud neck, and both Bnr1p-L1 and
      Bnr1p-L2 also show relatively stable localization there. Overexpression of Bnr1p
      L1, but not Bnr1p-L2, disrupts septin organization at the bud neck. Thus Bnr1p
      has two separable regions that each contribute to its bud neck localization.

PMID- 20147450
TI  - Genetic and structural relationships of Salmonella O55 and Escherichia coli O103
      O-antigens and identification of a 3-hydroxybutanoyltransferase gene involved in
      the synthesis of a Fuc3N derivative.
AB  - O-antigen (O-polysaccharide), a part of the outer membrane of Gram-negative
      bacteria, is one of the most variable cell constituents and is related to
      bacterial virulence. O-antigen diversity is almost entirely due to genetic
      variations in O-antigen gene clusters. In this study, the O-polysaccharide
      structures of Salmonella O55 and Escherichia coli O103 were elucidated by
      chemical analysis and nuclear magnetic resonance spectroscopy. It was found that
      the O-polysaccharides have similar pentasaccharide O-units, which differ only in
      one sugar (glucose versus N-acetylglucosamine) and in the N-acyl group (acetyl
      versus 3-hydroxybutanoyl) on 3-amino-3,6-dideoxy-d-galactose (d-Fuc3N). The
      Salmonella O55 antigen gene cluster was sequenced and compared with the E. coli
      O103 antigen gene cluster reported previously. The two gene clusters were found
      to share high-level similarity (DNA identity ranges from 53% to 76%), except for
      two putative acyl transferase genes (fdtC in Salmonella O55 and fdhC in E. coli
      O103) which show no similarity. Replacement of the fdtC gene in Salmonella O55
      with the fdhC gene from E. coli O103 resulted in production of a modified O
      antigen, which contains a 3-hydroxybutanoyl derivative of Fuc3N in place of 3
      acetamido-3,6-dideoxygalactose. This finding strongly suggests that fdhC is a 3
      hydroxybutanoyltransferase gene. The sequence similarity level suggested that the
      O-antigen gene clusters of Salmonella O55 and E. coli O103 originate from a
      common ancestor, and this evolutionary relationship is discussed.

PMID- 20147451
TI  - Sulfated alpha-L-galactans from the sea urchin ovary: selective 6-desulfation as
      eggs are spawned.
AB  - The sea urchin eggs are surrounded by a jelly coat, which contains sulfated
      polysaccharides with unique structures. These molecules are responsible for
      inducing the species-specific acrosome reaction, an obligatory event for the
      binding of sperm and fusion with the egg. The mechanism of biosynthesis of these
      sulfated polysaccharides is virtually unknown. The egg jelly of the sea urchin
      Echinometra lucunter contains a simple 2-sulfated, 3-linked alpha-L-galactan.
      Here, we pulse labeled the sea urchin ovary in vitro with (35)S-sulfate to follow
      the biosynthesis of the sulfated alpha-L-galactan. We found that the ovary
      contains a 2,6-disulfated, 3-linked alpha-L-galactan, which incorporates (35)S
      sulfate more avidly than the 2-sulfated isoform. The 2,6-disulfated alpha-L
      galactan was purified by anion exchange chromatography, analyzed by
      electrophoresis and characterized by 1D and 2D nuclear magnetic resonance
      spectra. We also investigated the location of the sulfated polysaccharides on the
      oocytes using histochemical procedures. The stain revealed high amounts of
      sulfated polysaccharide in mature oocytes and accessory cells. The amount of
      intracellular sulfated polysaccharides decreased as oocytes are spawned. We
      speculate that 2,6-disulfated galactan is initially synthesized in the ovary and
      that 6-sulfate ester is removed when the polysaccharide is secreted into the egg
      jelly. Similar events related to remodeling of sulfated polysaccharides have been
      reported in other biological systems.

PMID- 20147449
TI  - Initial polarized bud growth by endocytic recycling in the absence of actin cable
      dependent vesicle transport in yeast.
AB  - The assembly of filamentous actin is essential for polarized bud growth in
      budding yeast. Actin cables, which are assembled by the formins Bni1p and Bnr1p,
      are thought to be the only actin structures that are essential for budding.
      However, we found that formin or tropomyosin mutants, which lack actin cables,
      are still able to form a small bud. Additional mutations in components for
      cortical actin patches, which are assembled by the Arp2/3 complex to play a
      pivotal role in endocytic vesicle formation, inhibited this budding. Genes
      involved in endocytic recycling were also required for small-bud formation in
      actin cable-less mutants. These results suggest that budding yeast possesses a
      mechanism that promotes polarized growth by local recycling of endocytic
      vesicles. Interestingly, the type V myosin Myo2p, which was thought to use only
      actin cables to track, also contributed to budding in the absence of actin
      cables. These results suggest that some actin network may serve as the track for
      Myo2p-driven vesicle transport in the absence of actin cables or that Myo2p can
      function independent of actin filaments. Our results also show that polarity
      regulators including Cdc42p were still polarized in mutants defective in both
      actin cables and cortical actin patches, suggesting that the actin cytoskeleton
      does not play a major role in cortical assembly of polarity regulators in budding
      yeast.

PMID- 20147452
TI  - Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit
      auto-activation and its implication in sunitinib resistance.
AB  - The activation of receptor tyrosine kinases (RTKs) is tightly regulated through a
      variety of mechanisms. Kinetic studies show that activation of c-Kit RTK occurs
      through an inter-molecular autophosphorylation. Phosphopeptide mapping of c-Kit
      reveals that 14-22 phosphates are added to each mol of wild-type (WT) c-Kit
      during the activation. Phosphorylation sites are found on the JM, kinase insert
      (KID), c-terminal domains and the activation loop (A-loop), but only the sites on
      the JM domain contribute to the kinase activation. The A-loop tyrosine (Y(823))
      is not phosphorylated until very late in the activation (>90% completion),
      indicating that the A-loop phosphorylation is not required for c-Kit activation.
      A sunitinib-resistant mutant D816H that accelerates auto-activation by 184-fold
      shows no phosphorylation on the A-loop tyrosine after full activation. A loss-of
      phosphorylation mutation Y823F remains fully competent in auto-activation.
      Similar to WT and D816H, the unactivated Y823F mutant binds sunitinib and
      imatinib with high affinity (K(D) = 5.9 nM). But unlike the WT and D816H where
      the activated enzymes lose the ability to bind the two drugs, activated Y823F
      binds the two inhibitors effectively. These observations suggest that the A-loop
      of activated Y823F remains flexible and can readily adopt unactivated
      conformations to accommodate DFG-out binders.

PMID- 20147453
TI  - Isolation and characterization of antibodies against three consecutive Tn-antigen
      clusters from a phage library displaying human single-chain variable fragments.
AB  - The Tn-antigen, GalNAcalpha-Ser/Thr, is a tumour-associated carbohydrate antigen
      that may provide a sensitive and specific marker for pre-clinical detection of
      carcinoma and a target for cancer therapies. We recently reported that MLS128
      monoclonal antibody treatment significantly inhibited colon and breast cancer
      cell growth. On the basis of our observations, the present study aimed to produce
      human anti-Tn-antigen antibodies with specificity similar to that of MLS128
      monoclonal antibody, which recognizes a structure of three consecutive Tn
      antigens (Tn3). Six phage clones displaying human single-chain variable fragments
      (scFvs) were isolated from a newly constructed phage library by panning and
      screening with a synthetic Tn3-peptide. Deduced amino-acid sequences of six anti
      Tn3 scFvs exhibited a high degree of homology. Of those, anti-Tn3 4E10 and 4G2
      scFv proteins were successfully purified from phage-infected Escherichia coli to
      near homogeneity. Surface plasmon resonance analyses revealed a K(D) of purified
      scFv proteins for Tn3 on an order of 10(-7) M, which is high for carbohydrate
      specific monovalent antibodies. Further analyses suggested that both scFv
      proteins also bind to Tn2 and cultured colon and breast cancer cells. These
      results demonstrated the potential for use of these scFvs in developing antibody
      therapeutics targeting colon and breast cancer.

PMID- 20147456
TI  - Behind the mask: the influence of mask-type on amygdala response to fearful
      faces.
AB  - In this study, we compared the effects of using neutral face masks vs non-face
      pattern masks on amygdala activity to masked fearful faces. Twenty-seven subjects
      viewed 18 s blocks of either fearful or happy faces masked with either neutral
      faces or patterns, while their brain activity was measured using functional
      magnetic resonance imaging. Results replicated increased amygdala activation to
      face-masked fearful vs happy faces. In the pattern mask condition, the amygdala
      discriminated between masked fearful and happy faces, but this effect manifested
      as a decrease in activation to fearful faces compared to happy faces. This
      interactive effect between facial expression and mask stimulus shows that
      amygdala responses to masked fearful faces are influenced by the fearful stimuli
      per se as well as their interaction with the mask stimulus.

PMID- 20147454
TI  - Assessment and familial aggregation of psychosis in Alzheimer's disease from the
      National Institute on Aging Late Onset Alzheimer's Disease Family Study.
AB  - Determining the genetic architecture of late onset Alzheimer's disease remains an
      important research objective. One approach to the identification of novel genetic
      variants contributing to the disease is the classification of biologically
      meaningful subgroups within the larger late-onset Alzheimer's disease phenotype.
      The occurrence of psychotic symptoms in patients with late-onset Alzheimer's
      disease may identify one such group. We attempted to establish methods for the
      reliable assessment of psychotic symptoms in a large, geographically dispersed
      collection of families, multiply affected with late onset Alzheimer's disease,
      who were participants in the larger National Institute on Aging Late Onset
      Alzheimer's Disease Family Study; and to characterize the correlates and familial
      aggregation of psychosis within this cohort. We found that reliable assessments
      of psychotic symptoms during in-person or phone interviews were readily
      implemented. The presence of psychosis in late onset Alzheimer's disease was
      significantly associated with degree of cognitive impairment, and significantly,
      albeit modestly, correlated with the severity of other behavioural symptoms.
      Psychosis significantly aggregated within late onset Alzheimer's disease families
      suggesting that it may identify a genetically determined subgroup. Future studies
      should examine the linkage and association of psychosis with genetic variation
      within these families.

PMID- 20147455
TI  - Astrocytes within multiple sclerosis lesions upregulate sodium channel Nav1.5.
AB  - Astrocytes are prominent participants in the response of the central nervous
      system to injury, including neuroinflammatory insults. Rodent astrocytes in vitro
      have been shown to express voltage-gated sodium channels in a dynamic manner,
      with a switch in expression of tetrodotoxin-sensitive to tetrodotoxin-resistant
      channels in reactive astrocytes. However, the expression of sodium channels in
      human astrocytes has not been studied, and it is not known whether there are
      changes in the expression of sodium channels in reactive astrocytes of the human
      central nervous system. Here, we demonstrate a focal and robust upregulation of
      sodium channel Nav1.5 in reactive astrocytes at the borders of, and within,
      active and chronic multiple sclerosis lesions. Nav1.5 was only detectable at very
      low levels in astrocytes within multiple sclerosis macroscopically normal
      appearing white matter or in normal control brain. Nav1.1, Nav1.2, Nav1.3 and
      Nav1.6 showed little or no expression in astrocytes within normal control tissue
      and limited upregulation in active multiple sclerosis lesions. Nav1.5 was also
      expressed at high levels in astrocytes in tissue surrounding new and old
      cerebrovascular accidents and brain tumours. These results demonstrate the
      expression of Nav1.5 in human astrocytes and show that Nav1.5 expression is
      dynamic in these cells. Our observations suggest that the upregulated expression
      of Nav1.5 in astrocytes may provide a compensatory mechanism, which supports
      sodium/potassium pump-dependent ionic homoeostasis in areas of central nervous
      system injury.

PMID- 20147457
TI  - Individual differences in dispositional mindfulness and brain activity involved
      in reappraisal of emotion.
AB  - The regulation of negative emotion through reappraisal has been shown to induce
      increased prefrontal activity and decreased amygdala activity. Individual
      differences in dispositional mindfulness reflect differences in typical
      recognition, detachment and regulation of current experience, thought to also
      operate as top-down control mechanism. We sought to investigate whether such
      individual differences would be associated with brain activity elicited during
      reappraisal of negative emotion. Eighteen healthy participants completed a
      functional magnetic resonance imaging task that involved attending to or
      reappraising negative stimuli, and provided emotion experience ratings after each
      trial. Dispositional mindfulness was assessed with a self-report questionnaire.
      Reappraisal induced activity in a brain network involving predominantly dorsal
      portions of the prefrontal cortex, replicating previous studies. A voxelwise
      regression analysis showed that individual differences in the tendency to be
      mindful predicted activity in neural regions underlying reappraisal, with
      dorsomedial prefrontal cortex activation increasing with more mindfulness traits.
      Notably, this prefrontal activation was inversely correlated with the amygdala
      response to negative scenes, further supporting its role in down-regulating
      emotion-generation regions. These findings suggest that individual differences in
      dispositional mindfulness, which reflect the tendency to recognize and regulate
      current states, may modulate activity in neural systems involved in the effective
      cognitive control of negative emotion.

PMID- 20147458
TI  - Behavioral activation system modulation on brain activation during appetitive and
      aversive stimulus processing.
AB  - The reinforcement sensitivity theory (RST) proposed the behavioral activation
      system (BAS) as a neurobehavioral system that is dependent on dopamine-irrigated
      structures and that mediates the individual differences in sensitivity and
      reactivity to appetitive stimuli associated with BAS-related personality traits.
      Theoretical developments propose that high BAS sensitivity is associated with
      both enhanced appetitive stimuli processing and the diminished processing of
      aversive stimuli. The objective of this study was to analyze how individual
      differences in BAS functioning were associated with brain activation during
      erotic and aversive picture processing while subjects were involved in a simple
      goal-directed task. Forty-five male participants took part in this study. The
      task activation results confirm the activation of the reward and punishment brain
      related structures while viewing erotic and aversive pictures, respectively. The
      SR scores show a positive correlation with activation of the left lateral
      prefrontal cortex, the mesial prefrontal cortex and the right occipital cortex
      while viewing erotic pictures, and a negative correlation with the right lateral
      prefrontal cortex and the left occipital cortex while viewing aversive pictures.
      In summary, the SR scores modulate the activity of the cortical areas in the
      prefrontal and the occipital cortices that are proposed to modulate the BAS and
      the BIS-FFFS.

PMID- 20147459
TI  - Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and
      TGF-beta effectors.
AB  - Smad1 is a downstream effector of the BMP signaling pathway that binds regulatory
      DNA to execute gene expression programs leading to, for example, the maintenance
      of pluripotency in mice. On the contrary, the TGF-beta-activated Smad3 triggers
      strikingly different programs such as mesodermal differentiation in early
      development. Because Smad1 and Smad3 contain identical amino acids at the DNA
      contact interface it is unclear how they elicit distinctive bioactivities. Here,
      we report the crystal structure of the MH1 domain of Smad1 bound to a palindromic
      Smad binding element. Surprisingly, the DNA contact interface of Smad1 is
      drastically rearranged when compared to Smad3. The N-terminal helix 1 of Smad1 is
      dislodged from its intramolecular binding site and adopts a domain swapped
      arrangement with a symmetry-related molecule. As a consequence, helix 2 kinks
      away from the double helix disabling several key phosphate backbone interactions.
      Thermal melting analysis corroborates a decompacted conformation of Smad1 and DNA
      binding assays indicate a lower overall affinity of Smad1 to DNA but increased
      cooperativity when binding to palindromic DNA motifs. These findings suggest that
      Smad1 and Smad3 evolved differential qualities to assemble on composite DNA
      elements and to engage in co-factor interactions by remodeling their N-termini.

PMID- 20147460
TI  - Slow non-specific accumulation of 2'-deoxy and 2'-O-methyl oligonucleotide probes
      at mitochondria in live cells.
AB  - Molecular beacons (MBs) have the potential to provide a powerful tool for rapid
      RNA detection in living cells, as well as monitoring the dynamics of RNA
      expression in response to external stimuli. To exploit this potential, it is
      necessary to distinguish true signal from background signal due to non-specific
      interactions. Here, we show that, when cyanine-dye labeled 2'-deoxy and 2'-O
      methyl oligonucleotide probes are inside living cells for >5 h, most of their
      signals co-localize with mitochondrial staining. These probes include random
      sequence MB, dye-labeled single-strand linear oligonucleotide and dye-labeled
      double-stranded oligonucleotide. Using carbonyl cyanide m-chlorophenyl hydrazone
      treatment, we found that the non-specific accumulation of oligonucleotide probes
      at mitochondria was driven by mitochondrial membrane potential. We further
      demonstrated that the dye-labeled oligonucleotide probes were likely on/near the
      surface of mitochondria but not inside mitochondrial inner membrane.
      Interestingly, oligonucleotides probes labeled respectively with Alexa Fluor 488
      and Alexa Fluor 546 did not accumulate at mitochondria, suggesting that the non
      specific interaction between dye-labeled ODN probes and mitochondria is dye
      specific. These results may help design and optimize fluorescence imaging probes
      for long-time RNA detection and monitoring in living cells.

PMID- 20147461
TI  - Leishmania actin binds and nicks kDNA as well as inhibits decatenation activity
      of type II topoisomerase.
AB  - Leishmania actin (LdACT) is an unconventional form of eukaryotic actin in that it
      markedly differs from other actins in terms of its filament forming as well as
      toxin and DNase-1-binding properties. Besides being present in the cytoplasm,
      cortical regions, flagellum and nucleus, it is also present in the kinetoplast
      where it appears to associate with the kinetoplast DNA (kDNA). However, nothing
      is known about its role in this organelle. Here, we show that LdACT is indeed
      associated with the kDNA disc in Leishmania kinetoplast, and under in vitro
      conditions, it specifically binds DNA primarily through electrostatic
      interactions involving its unique DNase-1-binding region and the DNA major
      groove. We further reveal that this protein exhibits DNA-nicking activity which
      requires its polymeric state as well as ATP hydrolysis and through this activity
      it converts catenated kDNA minicircles into open form. In addition, we show that
      LdACT specifically binds bacterial type II topoisomerase and inhibits its
      decatenation activity. Together, these results strongly indicate that LdACT could
      play a critical role in kDNA remodeling.

PMID- 20147462
TI  - ATR contributes to telomere maintenance in human cells.
AB  - Telomere maintenance is essential to preserve genomic stability and involves
      several telomere-specific proteins as well as DNA replication and repair
      proteins. The kinase ATR, which has a crucial function in maintaining genome
      integrity from yeast to human, has been shown to be involved in telomere
      maintenance in several eukaryotic organisms, including yeast, Arabidopsis and
      Drosophila. However, its role in telomere maintenance in mammals remains poorly
      explored. Here, we report by using telomere-fluorescence in situ hybridization
      (Telo-FISH) on metaphase chromosomes that ATR deficiency causes telomere
      instability both in primary human fibroblasts from Seckel syndrome patients and
      in HeLa cells. The telomere aberrations resulting from ATR deficiency (i.e.
      sister telomere fusions and chromatid-type telomere aberrations) are mainly
      generated during and/or after telomere replication, and involve both leading and
      lagging strand telomeres as shown by chromosome orientation-FISH (CO-FISH).
      Moreover, we show that ATR deficiency strongly sensitizes cells to the G
      quadruplex ligand 360A, enhancing sister telomere fusions and chromatid-type
      telomere aberrations involving specifically the lagging strand telomeres.
      Altogether, these data reveal that ATR plays a critical role in telomere
      maintenance during and/or after telomere replication in human cells.

PMID- 20147463
TI  - A psyllium fiber-enriched meal strongly attenuates postprandial gastrointestinal
      peptide release in healthy young adults.
AB  - Dietary fiber (DF) and protein are essential constituents of a healthy diet and
      are well known for their high satiety impact. However, little is known about
      their influence on postprandial gastrointestinal (GI) peptide release. Our aim in
      this single-blind, randomized, cross-over study was to investigate the effects of
      DF and/or protein enrichments on satiety-related metabolic and hormonal
      responses. Sixteen healthy, nonobese volunteers participated in the study and
      ingested 1 of 5 isoenergetic test meals in a randomized order on separate days.
      The test meals were as follows: 1) low in protein (2.8 g) and fiber (7.6 g); 2)
      low in protein (2.6 g) and high in soluble fiber (psyllium, 23.0 g); 3) high in
      protein (soy, 19.7 g) and low in fiber (6.2 g); 4) high in protein (18.4 g) and
      fiber (23.0 g); and 5) white wheat bread. Serum insulin and plasma glucose,
      ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) concentrations
      were determined for 2 h following the meals. In addition, hunger and satiety
      ratings were collected. Postprandial glucose, insulin, ghrelin, GLP-1, and PYY
      responses all differed among the meals (P <or= 0.05). Fiber-enriched meals
      decreased glucose, insulin, ghrelin, and PYY responses; in addition, PYY
      secretion was prolonged compared with the other meals. The postprandial GLP-1
      concentration was significantly suppressed after a fiber- and protein-rich meal,
      in contrast to the initial increases following the other meals. However,
      postprandial ratings of appetite were mostly similar after the test meals. In
      conclusion, solid meals enriched with psyllium fiber strongly modified
      postprandial signals arising from the GI tract.

PMID- 20147464
TI  - Epidermal growth factor-expressing Lactococcus lactis enhances intestinal
      development of early-weaned pigs.
AB  - Stress and incomplete gastrointestinal development in early-weaned piglets
      represent significant challenges in commercial swine farming. Orally ingested
      recombinant epidermal growth factor (EGF) has been shown to remain biologically
      active in the gastrointestinal tract as well as stimulate intestinal development,
      reducing the incidence of pathogen infection and diarrhea. We have previously
      shown that the food-grade bacterium Lactococcus lactis can be genetically altered
      to express biologically active EGF when fed to early-weaned mice. In this study,
      we assigned 8 pigs to each of 4 groups that were given EGF-expressing L. lactis
      (EGF-LL), empty vector-expressing L. lactis (EV-LL), recombinant human EGF, or
      unsupplemented bacterial media, all of which were delivered as 50-mL i.g. doses
      twice per day. All pigs were killed after 14 d to examine intestinal morphology.
      Pigs in the EGF-LL group had greater jejunal and duodenal villus heights (P <
      0.0001) and intestinal length (P = 0.049) than pigs in the control group.
      Immunohistochemistry with antibodies against proliferating cell nuclear antigen
      (PCNA) revealed that the proliferation of intestinal cells was significantly
      greater in the EGF-LL group than in the control group. PCNA expression and
      intestinal length also were greater in the EV-LL group, which received L. lactis
      that did not express EGF, than in the control group (P = 0.049), further
      supporting the use of naturally occurring intestinal microbes as desirable
      vectors for recombinant protein delivery. Our data demonstrates the feasibility
      of delivering a growth factor using common probiotic bacteria to farm animals for
      commercial practice.

PMID- 20147465
TI  - Is it time to change guidelines for iron supplementation in malarial areas?

PMID- 20147466
TI  - DHA deficiency and prefrontal cortex neuropathology in recurrent affective
      disorders.
AB  - Increasing evidence suggests that docosahexaenoic acid [DHA, 22:6(n-3)], the
      principal (n-3) fatty acid in brain gray matter, has neurotrophic and
      neuroprotective properties. Preliminary clinical evidence also suggests that the
      perinatal accrual, and the subsequent dietary maintenance of, cortical DHA is
      positively associated with cortical gray matter volumes. The pathophysiology of
      recurrent affective disorders, including unipolar and bipolar depression, is
      associated with (n-3) fatty acid deficiency, DHA deficits, impaired astrocyte
      mediated vascular coupling, neuronal shrinkage, and reductions in gray matter
      volume in the prefrontal cortex (PFC). Preclinical studies have also observed
      neuronal shrinkage and indices of astrocyte pathology in the DHA-deficient rat
      brain. Together, this body of evidence supports the proposition that DHA
      deficiency increases vulnerability to neuronal atrophy in the PFC of patients
      with affective disorders. Because projections from the PFC modulate multiple
      limbic structures involved in affective regulation, this represents one plausible
      mechanism by which (n-3) fatty acid deficiency may increase vulnerability to
      recurrent affective disorders.

PMID- 20147467
TI  - Portion size can be used strategically to increase vegetable consumption in
      adults.
AB  - BACKGROUND: An increase in the proportion of vegetables at meals could help
      achieve recommended vegetable intakes and facilitate weight management.
      OBJECTIVE: We investigated the effects on food and energy intakes of varying the
      portion size and energy density of a vegetable that was added to a meal or
      substituted for other foods. DESIGN: In 2 experiments with crossover designs, men
      and women were served a meal of a vegetable, grain, and meat. Across the meals,
      the vegetable was served in 3 portion sizes (180, 270, or 360 g) and 2 energy
      densities (0.8 or 0.4 kcal/g) by altering the type and amount of added fat. In
      the addition study (n = 49), as the vegetable portion was increased, amounts of
      the grain and meat were unchanged, whereas in the substitution study (n = 48),
      amounts of the grain and meat decreased equally. RESULTS: An increase in the
      vegetable portion size resulted in greater vegetable consumption in both studies
      (mean +/- SE: 60 +/- 5 g; P < 0.0001). The addition of more of the vegetable did
      not significantly affect meal energy intake, whereas substitution of the
      vegetable for the grain and meat decreased meal energy intake (40 +/- 10 kcal; P
      < 0.0001). A reduction in vegetable energy density decreased meal energy intake
      independent of portion size (55 +/- 9 kcal; P < 0.0001). By combining
      substitution with a reduction in energy density, meal energy intake decreased by
      14 +/- 3%. CONCLUSIONS: Serving more vegetables, either by adding more or
      substituting them for other foods, is an effective strategy to increase vegetable
      intake at a meal. However, to moderate meal energy intake, vegetables should be
      low in energy density; furthermore, the substitution of vegetables for more
      energy-dense foods is more effective than simply adding extra vegetables.

PMID- 20147468
TI  - Guiding stars: the effect of a nutrition navigation program on consumer purchases
      at the supermarket.
AB  - BACKGROUND: To improve diet quality and overall population health, the need to
      develop nutritional rating systems that are comprehensive in scope and easy for
      the consumer to understand and use at the point-of-purchase has emerged.
      OBJECTIVE: Our aim was to examine the effect of a comprehensive storewide
      supermarket point-of-purchase nutrition navigation intervention by using a shelf
      label 3-tiered star icon on consumer food and beverage choices and their
      associated nutritional quality. DESIGN: By using a natural experiment design,
      purchasing data from 2006 to 2008 were obtained from a Northeast supermarket
      chain with 168 stores located in northern New England and New York and examined
      at preimplementation and at 1- and 2-y follow-up periods. RESULTS: The nutrition
      navigation system studied showed significant changes in food purchasing
      immediately after implementation, and these changes continued to be significant 1
      and 2 y later. When the same 8-mo period (January-August) each year was compared,
      in 2006, 24.50% of items purchased earned a star rating; this proportion
      increased to 24.98% (P < 0.001) and 25.89% (P < 0.0001) at the 1- and 2-y follow
      up periods, respectively. For a 4-wk period, 1 y after program implementation,
      consumers purchased significantly more ready-to-eat cereals with stars (eg, less
      added sugars and more dietary fiber) and fewer no-star, high-sugar, low-fiber
      cereals. CONCLUSION: Increasing rates of obesity and declining diet quality for
      Americans strongly support the need for effective supermarket point-of-purchase
      programs, such as the Guiding Stars nutrition navigation program, that provide
      clear, concise, and simplified nutrition information to guide consumer food and
      beverage choices.

PMID- 20147469
TI  - Reduced caloric intake during endotoxemia reduces arginine availability and
      metabolism.
AB  - BACKGROUND: Inadequate caloric intake increases the risk of sepsis-induced
      complications. Metabolic changes during sepsis indicate that the availability of
      the amino acid l-arginine decreases. Availability of arginine may further
      decrease during reduced caloric intake, which thereby limits the adaptive
      response of arginine-nitric oxide metabolism during sepsis. OBJECTIVE: We tested
      the hypothesis that reduced caloric intake during endotoxemia, as an experimental
      model for sepsis, further reduces arginine availability. DESIGN: In a randomized
      trial, a 7-d reduced caloric intake feed regimen (RE; n = 9) was compared with a
      normal control feed regimen (CE; n = 9), before 24 h of endotoxemia, as a model
      for sepsis. Whole-body arginine-nitric oxide metabolism and protein metabolism
      were measured by using a stable-isotope infusion of [(15)N(2)]arginine, [(13)C
      (2)H(2)]citrulline, [(2)H(5)]phenylalanine, and [(2)H(2)]tyrosine. Plasma
      pyruvate and lactate concentrations were determined by fully automated HPLC.
      RESULTS: Pre-endotoxin arginine appearance was significantly lower in the RE
      group than in the CE group (P = 0.002). During endotoxemia, arginine appearance
      increased in the CE animals but not in the RE animals (P = 0.04). In addition,
      nitric oxide production was significantly lower in the RE animals (P < 0.0001).
      Protein synthesis was significantly lower at the start of endotoxin infusion (P <
      0.05) and remained lower during endotoxemia in the RE group than in the CE group
      (P < 0.001). The lactate:pyruvate ratio was not higher in the RE group than in
      the CE group before endotoxemia but increased significantly during endotoxemia in
      the RE group (P = 0.04). CONCLUSION: A well-nourished condition before prolonged
      endotoxemia results in a better ability to adapt to endotoxin-induced metabolic
      deterioration of arginine-nitric oxide metabolism than does reduced caloric
      intake before endotoxemia.

PMID- 20147470
TI  - Nutritional aspects of HIV-associated wasting in sub-Saharan Africa.
AB  - The twin global epidemics of HIV infection and food scarcity disproportionately
      affect sub-Saharan Africa, and a significant proportion of patients who require
      antiretroviral therapy (ART) are malnourished because of a combination of HIV
      associated wasting and inadequate nutrient intake. Protein-calorie malnutrition,
      the most common form of adult malnutrition in the region, is associated with
      significant morbidity and compounds the immunosuppressive effects of HIV. A low
      body mass index (BMI), a sign of advanced malnutrition, is an independent
      predictor of early mortality (<6 mo) after ART initiation in several analyses,
      and recent studies show an association between early weight gain when receiving
      ART and improved treatment outcomes. The cause of the observed increase in
      mortality is uncertain, but it is likely due in part to malnutrition-induced
      immune system dysfunction, a higher burden of opportunistic infections, and
      metabolic derangements. In this article, we describe the epidemiology of HIV
      infection and malnutrition in sub-Saharan Africa, potential causes of increased
      mortality after ART initiation among patients with a low BMI, recent studies on
      post-ART weight gain and treatment outcome, and trials of macronutrient
      supplementation from the region. We close by highlighting priority areas for
      future research.

PMID- 20147471
TI  - Differential effects of coffee on the risk of type 2 diabetes according to meal
      consumption in a French cohort of women: the E3N/EPIC cohort study.
AB  - BACKGROUND: Coffee consumption has been associated with a lower risk of diabetes,
      but little is known about the mechanisms responsible for this association,
      especially related to the time when coffee is consumed. OBJECTIVE: We examined
      the long-term effect of coffee, globally and according to the accompanying meal,
      and of tea, chicory, and caffeine on type 2 diabetes risk. DESIGN: This was a
      prospective cohort study including 69,532 French women, aged 41-72 y from the
      E3N/EPIC (Etude Epidemiologique aupres de Femmes de la Mutuelle Generale de
      l'Education Nationale/European Prospective Investigation into Cancer and
      Nutrition) cohort study, without diabetes at baseline. Food and drink intakes per
      meal were assessed by using a validated diet-history questionnaire in 1993-1995.
      RESULTS: During a mean follow-up of 11 y, 1415 new cases of diabetes were
      identified. In multivariable Cox regression models, the hazard ratio in the
      highest category of coffee consumption [> or =3 cups (375 mL)/d] was 0.73 (95%
      CI: 0.61, 0.87; P for trend < 0.001), in comparison with no coffee consumption.
      This inverse association was restricted to coffee consumed at lunchtime (hazard
      ratio: 0.66; 95% CI: 0.57, 0.76) when comparing >1.1 cup (125 mL)/meal with no
      intake. At lunchtime, this inverse association was observed for both regular and
      decaffeinated coffee and for filtered and black coffee, with no effect of
      sweetening. Total caffeine intake was also associated with a statistically
      significantly lower risk of diabetes. Neither tea nor chicory consumption was
      associated with diabetes risk. CONCLUSIONS: Our data support an inverse
      association between coffee consumption and diabetes and suggest that the time of
      drinking coffee plays a distinct role in glucose metabolism.

PMID- 20147472
TI  - Reducing obesity in early childhood: results from Romp & Chomp, an Australian
      community-wide intervention program.
AB  - BACKGROUND: There is growing evidence that community-based interventions can
      reduce childhood obesity in older children. OBJECTIVE: We aimed to determine the
      effectiveness of the Romp & Chomp intervention in reducing obesity and promoting
      healthy eating and active play in children aged 0-5 y. DESIGN: Romp & Chomp was a
      community-wide, multisetting, multistrategy intervention conducted in Australia
      from 2004 to 2008. The intervention occurred in a large regional city (Geelong)
      with a target group of 12,000 children and focused on community capacity building
      and environmental (political, sociocultural, and physical) changes to increase
      healthy eating and active play in early-childhood care and educational settings.
      The evaluation was repeat cross-sectional with a quasiexperimental design and
      comparison sample. Main outcome measures were body mass index (BMI), standardized
      BMI (zBMI; according to the Centers for Disease Control and Prevention 2000
      reference charts), and prevalence of overweight/obesity and obesity-related
      behaviors in children aged 2 and 3.5 y. RESULTS: After the intervention there was
      a significantly lower mean weight, BMI, and zBMI in the 3.5-y-old subsample and a
      significantly lower prevalence of overweight/obesity in both the 2- and 3.5-y-old
      subsamples (by 2.5 and 3.4 percentage points, respectively) than in the
      comparison sample (a difference of 0.7 percentage points; P < 0.05) compared with
      baseline values. Intervention child-behavioral data showed a significantly lower
      intake of packaged snacks (by 0.23 serving), fruit juice (0.52 serving), and
      cordial (0.43 serving) than that in the comparison sample (all P < 0.05).
      CONCLUSION: A community-wide multisetting, multistrategy intervention in early
      childhood settings can reduce childhood obesity and improve young children's
      diets. This trial was registered with the Australian Clinical Trials Registry at
      anzctr.org.au as ACTRN12607000374460.

PMID- 20147473
TI  - Rapid cellular enrichment of eicosapentaenoate after a single intravenous
      injection of a novel medium-chain triacylglycerol:fish-oil emulsion in humans.
AB  - BACKGROUND: Dietary deficiency in n-3 (omega-3) polyunsaturated fatty acids
      (PUFAs) prevails in Western populations and potentially results in adverse health
      outcomes. To circumvent the slow n-3 PUFA incorporation in phospholipids of key
      cells after oral supplementation, a new preparation for intravenous bolus
      injection was developed with 20 g triacylglycerols/100 mL of a mixture of 80%
      medium-chain triacylglycerols (MCTs) and 20% fish oil (FO) (wt:wt), and 0.4 g
      alpha-tocopherol/100 mL of the same mixture. OBJECTIVE: Our objective was to
      document the enrichment of n-3 PUFAs in leukocyte and platelet phospholipids
      after a bolus intravenous injection of MCT:FO in men. DESIGN: Twelve healthy male
      subjects received injections over a 5-min period of 50 mL of either MCT:FO or a
      control MCT:long-chain triacylglycerol (MCT:LCT) emulsion containing 20 g
      triacylglycerols/100 mL with equal amounts (wt:wt) of MCT and soybean
      triacylglycerols (LCT) and containing 0.02 g alpha-tocopherol/100 mL; after an 8
      wk interval, the subjects received injections of the other preparation. RESULTS:
      Clinical and biological variables that assessed tolerance and safety remained
      unchanged. Plasma elimination was faster for MCT:FO than for MCT:LCT (half-life:
      24.5 +/- 3.5 min compared with 32.9 +/- 3.0 min; P < 0.025). This was associated
      with a greater increase in the plasma nonesterified fatty acid concentration. The
      content of n-3 PUFAs, specifically eicosapentaenoic acid (20:5n-3), increased in
      leukocyte and platelet phospholipids within 60 min and > or =24 h after MCT:FO
      injection. CONCLUSION: Bolus intravenous injection of a novel MCT:FO emulsion
      allows rapid enrichment of cells with n-3 PUFAs.

PMID- 20147475
TI  - Guilt by association: the challenge of teasing apart the effect of various risk
      factors for coronary heart disease in systemic lupus erythematosus.

PMID- 20147474
TI  - Zinc and iron deficiency and their interrelations in low-income African American
      and Hispanic children in Atlanta.
AB  - BACKGROUND: Information about the zinc status of low-income minority children in
      the United States is lacking. OBJECTIVE: The objective was to determine the
      prevalence of zinc deficiency and anemia and their interrelation among low-income
      African American and Hispanic preschool children. DESIGN: This was a cross
      sectional study in which a prospective 3-d food diary was completed, and
      hemoglobin, serum ferritin, zinc, copper, and C-reactive protein concentrations
      were measured. Children with elevated C-reactive protein concentrations were
      excluded from analysis. RESULTS: Of 292 children recruited, 280 (mean +/- SD age:
      2.5 +/- 1.2 y) qualified for analysis. One hundred forty-six (52%) children were
      African American and 134 (48%) were Hispanic; 202 (72%) were enrolled in the
      Women, Infants, and Children nutrition program. A low serum zinc concentration
      (<10.7 mumol/L) was present in 34 (12%) children, and 37 (13%) were anemic
      (hemoglobin < 110 g/L). African American (odds ratio: 3.47; 95% CI: 1.51, 7.96)
      and anemic (odds ratio: 2.92; 95% CI: 1.24, 6.90) children had an increased risk
      of zinc deficiency. Serum zinc correlated with hemoglobin (r = 0.24, P < 0.001).
      Children with a height/length less than the fifth percentile had significantly
      lower mean serum zinc concentrations than those with a height/length greater than
      the fifth percentile (12.4 +/- 1.8 compared with 13.0 +/- 2.2 micromol/L; P <
      0.001). In a multiple logistic regression model, African American race-ethnicity
      was associated with zinc deficiency (odds ratio: 0.26; P = 0.02). The main
      sources of iron and zinc in the diets were meat products and cereals.
      CONCLUSIONS: The prevalence of zinc deficiency and anemia was high in this
      population of low-income minority children, especially among African Americans.
      Further investigation of the incidence of zinc deficiency and the ability of
      anemia to screen for it is warranted.

PMID- 20147476
TI  - Are reporting standards of diagnostic test evaluation unrealistic?

PMID- 20147477
TI  - Using utilities.

PMID- 20147478
TI  - Successful immunosuppressive treatment of dermatomyositis: a nailfold
      capillaroscopy survey.

PMID- 20147479
TI  - Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)
      2008.
AB  - The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
      (GRAPPA) is an international group dedicated to improving the lives of patients
      suffering from psoriasis and psoriatic arthritis (PsA). At the 2008 annual
      meeting of GRAPPA in Leeds, United Kingdom, members reviewed the status of
      imaging, including a new ultrasound measure, ultra-short echo time (UTE), and
      magnetic resonance imaging (MRI) in PsA and the imaging of musculoskeletal
      tissues in psoriasis; discussed the value and current status of composite
      measures for the assessment of PsA, including a breakout session where members
      addressed several issues related to developing PsA-specific composite measures;
      and reviewed biomarker development in psoriatic disease, including an interactive
      section on design considerations for a longitudinal study of biomarkers for joint
      damage. Summaries of those discussions are presented in this supplement.

PMID- 20147480
TI  - Imaging in psoriasis and psoriatic arthritis: GRAPPA 2008.
AB  - At the 2008 meeting of GRAPPA (Group for Research and Assessment of Psoriasis and
      Psoriatic Arthritis), the primary focus of the imaging session was the enthesis.
      Presentations from Dennis McGonagle (Leeds, UK), Richard Hodgson (Leeds, UK), and
      Paolo Gisondi (Verona, Italy) elaborated on this theme and prepared the meeting
      attendees for group discussions of further work in this area. Imaging, notably
      magnetic resonance imaging (MRI) and ultrasonography, provides evidence of
      pathological change at the enthesis in psoriatic arthritis (PsA). Further,
      imaging abnormalities are found at sites that are asymptomatic in both PsA and
      psoriasis. The role of newer imaging modalities, such as ultra-short echo time
      (UTE) MRI, is promising but remains to be fully elucidated. The implication of
      these findings in relation to subclinical and predisease status is intriguing and
      requires further study in longitudinal studies. Further work is also required to
      examine the proposed common biomechanical basis between joint and skin, the
      mechanism of the resulting inflammation, and how these mechanisms differ from
      those seen in rheumatoid arthritis.

PMID- 20147481
TI  - Composite measures in psoriatic arthritis: GRAPPA 2008.
AB  - At the 2008 annual meeting of GRAPPA (Group for Research and Assessment of
      Psoriasis and Psoriatic Arthritis) in Leeds, UK, members discussed the value and
      current status of composite measures for the assessment of psoriatic arthritis
      (PsA). In plenary presentations, examples of composite measures developed for
      rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were reviewed, followed
      by a presentation of the assessment of disease activity in systemic lupus
      erythematosus. Three recently devised composite methods of assessing activity or
      response in PsA also were presented. Considerable discussion followed in breakout
      groups, and members agreed that a new composite measure specifically for PsA is
      necessary. The composite measure should include components that encompass the
      spectrum of psoriatic disease, i.e., in addition to assessment of peripheral
      joints, it should include assessment of sacroiliitis, spondylitis, enthesitis,
      and dactylitis, as well as skin and nail disease.

PMID- 20147482
TI  - Biomarkers in psoriasis and psoriatic arthritis: GRAPPA 2008.
AB  - Biomarkers can provide valuable insights into disease susceptibility and natural
      history and may serve as surrogate endpoints for a variety of different outcomes.
      At the 2008 annual meeting of GRAPPA (Group for Research and Assessment of
      Psoriasis and Psoriatic Arthritis), members were updated on the development of
      biomarkers in psoriatic arthritis (PsA). Plenary presentations included a
      translational approach to biomarker development (Christopher Ritchlin, University
      of Rochester, NY, USA), biomarkers for psoriasis (Abrar Qureshi, Harvard Medical
      School, MA, USA), new data on biomarkers for damage in PsA (Kurt de Vlam,
      University Hospitals Leuven, Belgium), and design considerations for a
      longitudinal study of joint damage being undertaken under the OMERACT umbrella
      with colleagues working on rheumatoid arthritis and ankylosing spondylitis
      (Costantino Pitzalis, Barts and the London School of Medicine, London, UK; Oliver
      FitzGerald, St. Vincent's Hospital, Dublin, Ireland). At the conclusion of this
      session, the meeting attendees discussed specific design issues of the proposed
      longitudinal study, including study duration, disease process core domains, and
      the instruments to be used in recording enthesitis, dactylitis, nail involvement,
      quality of life and structural damage. The appearance of new therapeutic options
      in PsA raises the need for sensitive biomarkers for both disease activity and
      outcome.

PMID- 20147483
TI  - Disease activity composite indices in patients with rheumatoid arthritis and
      concomitant fibromyalgia.

PMID- 20147484
TI  - The story behind the acute-phase reactants.

PMID- 20147485
TI  - Neuromeningeal tuberculosis in a patient with rheumatoid arthritis previously
      exposed to ineffective etanercept therapy and revealed by infliximab.

PMID- 20147486
TI  - Ezetimibe-induced relapsing polymyositis.

PMID- 20147487
TI  - Endogenous retrovirus ERV-3 is not implicated in rheumatoid arthritis but may
      provide a biomarker for osteoarthritis.

PMID- 20147488
TI  - Accuracy of the ICD-9 code for identification of patients with Wegener's
      granulomatosis.

PMID- 20147490
TI  - Mathematical modeling-guided evaluation of biochemical, developmental,
      environmental, and genotypic determinants of essential oil composition and yield
      in peppermint leaves.
AB  - We have previously reported the use of a combination of computational simulations
      and targeted experiments to build a first generation mathematical model of
      peppermint (Menthaxpiperita) essential oil biosynthesis. Here, we report on the
      expansion of this approach to identify the key factors controlling monoterpenoid
      essential oil biosynthesis under adverse environmental conditions. We also
      investigated determinants of essential oil biosynthesis in transgenic peppermint
      lines with modulated essential oil profiles. A computational perturbation
      analysis, which was implemented to identify the variables that exert prominent
      control over the outputs of the model, indicated that the essential oil
      composition should be highly dependent on certain biosynthetic enzyme
      concentrations [(+)-pulegone reductase and (+)-menthofuran synthase], whereas oil
      yield should be particularly sensitive to the density and/or distribution of leaf
      glandular trichomes, the specialized anatomical structures responsible for the
      synthesis and storage of essential oils. A microscopic evaluation of leaf
      surfaces demonstrated that the final mature size of glandular trichomes was the
      same across all experiments. However, as predicted by the perturbation analysis,
      differences in the size distribution and the total number of glandular trichomes
      strongly correlated with differences in monoterpenoid essential oil yield.
      Building on various experimental data sets, appropriate mathematical functions
      were selected to approximate the dynamics of glandular trichome
      distribution/density and enzyme concentrations in our kinetic model. Based on a
      chi2 statistical analysis, simulated and measured essential oil profiles were in
      very good agreement, indicating that modeling is a valuable tool for guiding
      metabolic engineering efforts aimed at improving essential oil quality and
      quantity.

PMID- 20147489
TI  - Twelve-year follow-up of American women's awareness of cardiovascular disease
      risk and barriers to heart health.
AB  - BACKGROUND: Awareness of cardiovascular disease (CVD) risk has been linked to
      taking preventive action in women. The purpose of this study was to assess
      contemporary awareness of CVD risk and barriers to prevention in a nationally
      representative sample of women and to evaluate trends since 1997 from similar
      triennial surveys. METHODS AND RESULTS: A standardized survey about awareness of
      CVD risk was completed in 2009 by 1142 women >or=25 years of age, contacted
      through random digit dialing oversampled for racial/ethnic minorities, and by
      1158 women contacted online. There was a significant increase in the proportion
      of women aware that CVD is the leading cause of death since 1997 (P for
      trend=<0.0001). Awareness among telephone participants was greater in 2009
      compared with 1997 (54% versus 30%, P<0.0001) but not different from 2006 (57%).
      In multivariate analysis, African American and Hispanic women were significantly
      less aware than white women, although the gap has narrowed since 1997. Only 53%
      of women said they would call 9-1-1 if they thought they were having symptoms of
      a heart attack. The majority of women cited therapies to prevent CVD that are not
      evidence-based. Common barriers to prevention were family/caretaking
      responsibilities (51%) and confusion in the media (42%). Community-level changes
      women thought would be helpful were access to healthy foods (91%), public
      recreation facilities (80%), and nutrition information in restaurants (79%).
      CONCLUSIONS: Awareness of CVD as the leading cause of death among women has
      nearly doubled since 1997 but is stabilizing and continues to lag in
      racial/ethnic minorities. Numerous misperceptions and barriers to prevention
      persist and women strongly favored environmental approaches to facilitate
      preventive action.

PMID- 20147491
TI  - Nitric oxide mediates the hormonal control of Crassulacean acid metabolism
      expression in young pineapple plants.
AB  - Genotypic, developmental, and environmental factors converge to determine the
      degree of Crassulacean acid metabolism (CAM) expression. To characterize the
      signaling events controlling CAM expression in young pineapple (Ananas comosus)
      plants, this photosynthetic pathway was modulated through manipulations in water
      availability. Rapid, intense, and completely reversible up-regulation in CAM
      expression was triggered by water deficit, as indicated by the rise in nocturnal
      malate accumulation and in the expression and activity of important CAM enzymes.
      During both up- and down-regulation of CAM, the degree of CAM expression was
      positively and negatively correlated with the endogenous levels of abscisic acid
      (ABA) and cytokinins, respectively. When exogenously applied, ABA stimulated and
      cytokinins repressed the expression of CAM. However, inhibition of water deficit
      induced ABA accumulation did not block the up-regulation of CAM, suggesting that
      a parallel, non-ABA-dependent signaling route was also operating. Moreover,
      strong evidence revealed that nitric oxide (NO) may fulfill an important role
      during CAM signaling. Up-regulation of CAM was clearly observed in NO-treated
      plants, and a conspicuous temporal and spatial correlation was also evident
      between NO production and CAM expression. Removal of NO from the tissues either
      by adding NO scavenger or by inhibiting NO production significantly impaired ABA
      induced up-regulation of CAM, indicating that NO likely acts as a key downstream
      component in the ABA-dependent signaling pathway. Finally, tungstate or glutamine
      inhibition of the NO-generating enzyme nitrate reductase completely blocked NO
      production during ABA-induced up-regulation of CAM, characterizing this enzyme as
      responsible for NO synthesis during CAM signaling in pineapple plants.

PMID- 20147492
TI  - PlantMetabolomics.org: a web portal for plant metabolomics experiments.
AB  - PlantMetabolomics.org (PM) is a web portal and database for exploring,
      visualizing, and downloading plant metabolomics data. Widespread public access to
      well-annotated metabolomics datasets is essential for establishing metabolomics
      as a functional genomics tool. PM integrates metabolomics data generated from
      different analytical platforms from multiple laboratories along with the key
      visualization tools such as ratio and error plots. Visualization tools can
      quickly show how one condition compares to another and which analytical platforms
      show the largest changes. The database tries to capture a complete annotation of
      the experiment metadata along with the metabolite abundance databased on the
      evolving Metabolomics Standards Initiative. PM can be used as a platform for
      deriving hypotheses by enabling metabolomic comparisons between genetically
      unique Arabidopsis (Arabidopsis thaliana) populations subjected to different
      environmental conditions. Each metabolite is linked to relevant experimental data
      and information from various annotation databases. The portal also provides
      detailed protocols and tutorials on conducting plant metabolomics experiments to
      promote metabolomics in the community. PM currently houses Arabidopsis
      metabolomics data generated by a consortium of laboratories utilizing
      metabolomics to help elucidate the functions of uncharacterized genes. PM is
      publicly available at http://www.plantmetabolomics.org.

PMID- 20147493
TI  - Crystal structure and functional insights of hemopexin fold protein from grass
      pea.
AB  - A regulatory protein from grass pea (Lathyrus sativus), LS-24, a close homolog of
      albumin 2 from garden pea (Pisum sativum) that is associated with polyamine
      biosynthesis, was characterized and the structure of a hemopexin-type fold among
      plant proteins illustrated. Crystal structure of LS-24 determined at 2.2 A
      resolution by multiple isomorphous replacement phasing showed four-bladed beta
      propeller structure having a pseudo 4-fold molecular symmetry along a metal ion
      binding central channel. The structure represents typical mammalian hemopexin
      fold with discernible features correlated with the possible functional
      variations. The protein was found to exist in the dimeric state. While LS-24
      dimer binds to spermine in the crystal structure as well as in solution, binding
      of heme in solution resulted in the dissociation of the dimer into monomers with
      concomitant release of bound spermine. Interactions of heme and spermine with LS
      24 bear physiological implications. While binding of spermine to LS-24 can be
      linked with polyamine biosynthesis that of heme correlates with oxidative stress.
      Mutually exclusive binding of heme and spermine in different oligomeric states
      suggest a role for LS-24 in sensing oxidative stress through a ligand-regulated
      monomer-dimer transition switch.

PMID- 20147494
TI  - SUGAR-INSENSITIVE3, a RING E3 ligase, is a new player in plant sugar response.
AB  - Sugars, such as sucrose and glucose, have been implicated in the regulation of
      diverse developmental events in plants and other organisms. We isolated an
      Arabidopsis (Arabidopsis thaliana) mutant, sugar-insensitive3 (sis3), that is
      resistant to the inhibitory effects of high concentrations of exogenous glucose
      and sucrose on early seedling development. In contrast to wild-type plants, sis3
      mutants develop green, expanded cotyledons and true leaves when sown on medium
      containing high concentrations (e.g. 270 mm) of sucrose. Unlike some other sugar
      response mutants, sis3 exhibits wild-type responses to the inhibitory effects of
      abscisic acid and paclobutrazol, a gibberellic acid biosynthesis inhibitor, on
      seed germination. Map-based cloning revealed that SIS3 encodes a RING finger
      protein. Complementation of the sis3-2 mutant with a genomic SIS3 clone restored
      sugar sensitivity of sis3-2, confirming the identity of the SIS3 gene.
      Biochemical analyses demonstrated that SIS3 is functional in an in vitro
      ubiquitination assay and that the RING motif is sufficient for its activity. Our
      results indicate that SIS3 encodes a ubiquitin E3 ligase that is a positive
      regulator of sugar signaling during early seedling development.

PMID- 20147495
TI  - Promising rabies vaccine for postexposure prophylaxis in developing countries, a
      purified vero cell vaccine produced in china.
AB  - We evaluated the immunogenicity, safety, and antibody persistence of a Vero cell
      rabies vaccine manufactured in China, compared with those of Verorab. Adequate
      titers of antibody were observed for the two vaccines. ChengDa rabies vaccine
      could be a promising alternative vaccine for many developing countries which
      cannot afford expensive rabies vaccines.

PMID- 20147496
TI  - Comparison of three automated immunoassay methods for the determination of
      Epstein-Barr virus-specific immunoglobulin M.
AB  - In this study we compared the performances of three commercially available
      Epstein-Barr virus (EBV) immunoglobulin M (IgM) assays on highly automated
      immunoassay platforms: BioPlex 2200 (Bio-Rad Laboratories), Immulite 2000
      (Siemens Healthcare Diagnostics), and Liaison (DiaSorin). As a confirmatory
      method, immunoblotting was performed. The specificity of the three EBV IgM assays
      was evaluated by testing 293 selected sera from patients with various infectious
      and noninfectious diseases. After the exclusion of 30 samples, the specificities
      were 96.2% for Liaison, 98.1% for Immulite, and 97.0% for BioPlex. For evaluation
      of the sensitivity, samples from 70 consecutive patients with a positive
      heterophile antibody test were examined, irrespective of clinical or biological
      findings. After the exclusion of six samples, the sensitivities were 89.1% for
      Liaison, 84.4% for Immulite, and 89.1% for BioPlex. Finally, in a prospective
      study performed with 500 samples obtained from consecutive patients and sent in
      by general practitioners, we also determined Epstein-Barr nuclear antigen IgG and
      viral capsid antigen IgG in a two-phase approach. Concordance of the EBV
      serologic status was 96.2% between Liaison and Immulite, 96.4% between Immulite
      and BioPlex, and 97.8% between BioPlex and Liaison. The three EBV IgM
      immunoassays that we evaluated have acceptable and comparable performances.

PMID- 20147497
TI  - A novel surface antigen of relapsing fever spirochetes can discriminate between
      relapsing fever and Lyme borreliosis.
AB  - In a previous immunoproteome analysis of Borrelia hermsii, candidate antigens
      that bound IgM antibodies from mice and patients infected with relapsing fever
      spirochetes were identified. One candidate that was identified is a hypothetical
      protein with a molecular mass of 57 kDa that we have designated Borrelia
      immunogenic protein A (BipA). This protein was further investigated as a
      potential diagnostic antigen for B. hermsii given that it is absent from the
      Borrelia burgdorferi genome. The bipA locus was amplified and sequenced from 39
      isolates of B. hermsii that had been acquired from western North America. bipA
      was also expressed as a recombinant fusion protein. Serum samples from mice and
      patients infected with B. hermsii or B. burgdorferi were used to confirm the
      immunogenicity of the recombinant protein in patients infected with relapsing
      fever spirochetes. Lastly, in silico and experimental analysis indicated that
      BipA is a surface-exposed lipoprotein in B. hermsii. These findings enhance the
      capabilities of diagnosing infection with relapsing fever spirochetes.

PMID- 20147498
TI  - Evaluation of indirect enzyme-linked immunosorbent assays and IgG avidity assays
      using a protein A-peroxidase conjugate for serological distinction between
      Brucella abortus S19-vaccinated and -infected cows.
AB  - This study aimed to evaluate the use of protein A-peroxidase (horseradish
      peroxidase [HRPO]) in indirect enzyme-linked immunosorbent assays (iELISAs) and
      IgG avidity assays for serological distinction between Brucella abortus S19
      vaccinated and -infected cows. Four groups were analyzed: GI, 41 nonvaccinated
      seropositive cows; GII, 79 S19-vaccinated heifers analyzed at 3 months
      postvaccination; GIII, 105 S19-vaccinated cows analyzed after 24 months of age;
      and GIV, 278 nonvaccinated seronegative cows. IgG levels and avidity to B.
      abortus smooth lipopolysaccharide (S-LPS) were determined using anti-bovine IgG
      HRPO or protein A-HRPO conjugates. Similar levels of IgG anti-S-LPS were found
      with GI using both conjugates. Lower IgG levels were detected with GII, GIII, and
      GIV using protein A-HRPO. Both conjugates showed high performance in
      discriminating GI from GIII, with high sensitivity (Se; 97.6%) and specificity
      (Sp; 97.1%). Protein A-HRPO was better in distinguishing GI from GIV (Se, 97.6%;
      Sp, 94.6%) and GI from GII (Se, 80.5%; Sp, 94.9%). Protein A-HRPO excluded a
      higher number of positive samples with GII and GIV. IgG avidity showed that
      protein A-HRPO, but not anti-IgG-HRPO, was able to distinguish nonvaccinated from
      vaccinated cattle, showing a higher avidity index (AI) with GI than with GII,
      with 78% of serum samples in GII showing an AI of <50%. Therefore, the iELISA
      using B. abortus S-LPS antigen and protein A-HRPO conjugate for preferential
      detection of the IgG2 subclass was shown to be suitable for serological
      distinction between S19-vaccinated and -infected cows. Also, antibodies generated
      after vaccination showed lower avidity, suggesting a role for the IgG2 subclass
      as an antibody of higher-affinity maturation after infection, constituting an
      additional tool for differentiating vaccinated from infected cattle.

PMID- 20147503
TI  - A theoretical understanding of sickness absence among women who have experienced
      workplace bullying.
AB  - Historically, we have assumed that workplaces, where employed individuals spend
      approximately one third of their days, provide safe and supportive environments
      and opportunities to enhance women's capacities. Unfortunately, workplace
      bullying and consequent sickness absence are prevalent and costly realities that
      significantly influence women's health. In this study, sickness absence among 18
      Canadian women who were targets of workplace bullying was explored using a
      grounded theory secondary analysis. Findings show that although sickness absence
      is critical in attenuating the health consequences of being bullied, it is a
      partial solution because rehabilitation and successful return to work is
      challenged when working conditions remain unchanged. This problem is addressed
      using is a three-stage process of discerning a path that involves gaining space,
      making sense, and moving forward. Organizational support is critical to all
      stages of the process; it can reduce the risk of declines in health and sickness
      absence, and is essential for successful return to work.

PMID- 20147499
TI  - Salmonella enterica serovar Typhimurium vaccine strains expressing a nontoxic
      Shiga-like toxin 2 derivative induce partial protective immunity to the toxin
      expressed by enterohemorrhagic Escherichia coli.
AB  - Shiga-like toxin 2 (Stx2)-producing enterohemorrhagic Escherichia coli (referred
      to as EHEC or STEC) strains are the primary etiologic agents of hemolytic-uremic
      syndrome (HUS), which leads to renal failure and high mortality rates. Expression
      of Stx2 is the most relevant virulence-associated factor of EHEC strains, and
      toxin neutralization by antigen-specific serum antibodies represents the main
      target for both preventive and therapeutic anti-HUS approaches. In the present
      report, we describe two Salmonella enterica serovar Typhimurium aroA vaccine
      strains expressing a nontoxic plasmid-encoded derivative of Stx2 (Stx2DeltaAB)
      containing the complete nontoxic A2 subunit and the receptor binding B subunit.
      The two S. Typhimurium strains differ in the expression of flagellin, the
      structural subunit of the flagellar shaft, which exerts strong adjuvant effects.
      The vaccine strains expressed Stx2DeltaAB, either cell bound or secreted into the
      extracellular environment, and showed enhanced mouse gut colonization and high
      plasmid stability under both in vitro and in vivo conditions. Oral immunization
      of mice with three doses of the S. Typhimurium vaccine strains elicited serum
      anti-Stx2B (IgG) antibodies that neutralized the toxic effects of the native
      toxin under in vitro conditions (Vero cells) and conferred partial protection
      under in vivo conditions. No significant differences with respect to gut
      colonization or the induction of antigen-specific antibody responses were
      detected in mice vaccinated with flagellated versus nonflagellated bacterial
      strains. The present results indicate that expression of Stx2DeltaAB by
      attenuated S. Typhimurium strains is an alternative vaccine approach for HUS
      control, but additional improvements in the immunogenicity of Stx2 toxoids are
      still required.

PMID- 20147504
TI  - Identifying cultural representations of families and the health team to improve
      the management of severe malnutrition in childhood.
AB  - Severe childhood malnutrition is no longer a priority in Latin America, but
      mortality of hospitalized malnourished children continues to be high, especially
      in Bolivia. The objective of the present study was to identify cultural
      representations in mothers and in health personnel that might influence the
      relationship between the family and the provider's health care services, thus
      affecting the treatment of malnourished children. We applied a flexible
      qualitative model of cases and controls (mothers or caregivers of both under- and
      well-nourished children), and in addition, health personnel. Results were
      analyzed following semiotics of statements. Mothers and health professionals
      based their cultural representations on different conceptions of health. The
      mothers' mindset indicated that traditional Andean medicine and public health
      systems are complementary and not contradictory. Conversely, health personnel
      expressed a univocal vision, accepting only biomedicine. Furthermore, they also
      expressed a negative attitude toward mothers of severely malnourished children.
      Results should be considered to improve ongoing local health programs.

PMID- 20147505
TI  - How low-income mothers with overweight preschool children make sense of obesity.
AB  - Epidemiologic and qualitative studies have found that most mothers with
      overweight preschool children do not think their children are overweight. This
      might present a challenge for clinicians who wish to address obesity in young
      children. To understand mothers' perceptions of their overweight children's
      weight, we conducted semistructured interviews with 21 mothers of overweight
      preschool children enrolled in Kentucky's Special Supplemental Nutrition Program
      for Women, Infants, and Children. Although these mothers did not label their
      children as overweight, they were worried about children's weight, particularly
      as it related to their emotional well-being. These worries about obesity were
      reflected in three central tensions that shaped the way mothers perceived their
      children's weight and informed maternal feeding strategies: (a) nature vs.
      nurture, (b) medical authority vs. lived experience, and (c) relieving immediate
      stress vs. preventing long-term consequences. Acknowledging mothers' concerns and
      tensions might help clinicians communicate more effectively with them about
      obesity.

PMID- 20147506
TI  - The lived experience of girl-to-girl aggression in marginalized girls.
AB  - Girl-to-girl aggression is increasingly being recognized as a health problem, and
      the number of teenage girls involved in serious fighting is on the rise. Research
      on the experiences of girl-to-girl aggression in marginalized girls who are out
      of the mainstream because of poor relationship skills and physical aggression is
      notably absent, yet this group is at heightened risk for persistent violence. In
      this study I used the interpretive phenomenological approach to study the lived
      experience of girl-to-girl aggression in girls who were marginalized and
      attending an alternative school because of physically aggressive behavior. Data
      were collected over a 4-month period by means of in-depth interviews and field
      notes. For this population, girl-to-girl aggression provided self-protection,
      expressed girls' identity, and was also a means to finding attachment,
      connection, and friendship. These findings have multidisciplinary implications
      for interventions with physically aggressive girls, including mentoring programs,
      in-school support groups, and exploration of a paradigm shift in the use of
      alternative schools.

PMID- 20147507
TI  - Current management of gallbladder carcinoma.
AB  - Gallbladder cancer (GBC) represents the most common and aggressive type among the
      biliary tree cancers (BTCs). Complete surgical resection offers the only chance
      for cure; however, only 10% of patients with GBC present with early-stage disease
      and are considered surgical candidates. Among those patients who do undergo
      "curative" resection, recurrence rates are high. There are no established
      adjuvant treatments in this setting. Patients with unresectable or metastatic GBC
      have a poor prognosis. There has been a paucity of randomized phase III data in
      this field. A recent report demonstrated longer overall survival with gemcitabine
      in combination with cisplatin than with gemcitabine alone in patients with
      advanced or metastatic BTCs. Molecularly targeted agents are under development.
      In this review, we attempt to discuss the current status and key issues involved
      in the management of GBC.

PMID- 20147514
TI  - Perceived social competency in children with brain tumors: comparison between
      children on and off therapy.
AB  - Children with brain tumors are at risk for a number of cognitive, academic, and
      social difficulties as a consequence of their illness and its treatment. Of
      these, the least is known about social functioning, particularly over the course
      of the illness. Thirty children with brain tumors were evaluated using
      neurocognitive and psychological measures, including a measure of perceived
      competency. Results indicated that off-therapy brain tumor patients reported more
      concerns about their social competence than both a normative sample and children
      on treatment. Findings highlight the need for more research aimed at helping
      survivors cope with long-term stressors associated with their illness.

PMID- 20147515
TI  - A novel transmembrane domain mediating retention of a highly motile herpesvirus
      glycoprotein in the endoplasmic reticulum.
AB  - Gene m164 of murine cytomegalovirus belongs to the large group of 'private' genes
      that show no homology to those of other cytomegalovirus species and are thought
      to represent 'host adaptation' genes involved in virus-host interaction. Previous
      interest in the m164 gene product was based on the presence of an immunodominant
      CD8 T-cell epitope presented at the surface of infected cells, despite
      interference by viral immune-evasion proteins. Here, we provide data to reveal
      that the m164 gene product shows unusual features in its cell biology. A novel
      strategy of mass-spectrometric analysis was employed to map the N terminus of the
      mature protein, 107 aa downstream of the start site of the predicted open reading
      frame. The resulting 36.5 kDa m164 gene product is identified here as an integral
      type-I membrane glycoprotein with exceptional intracellular trafficking dynamics,
      moving within the endoplasmic reticulum (ER) and outer nuclear membrane with an
      outstandingly high lateral membrane motility, actually 100 times higher than
      those published for cellular ER-resident proteins. Notably, gp36.5/m164 does not
      contain any typical ER-retention/retrieval signals, such as the C-terminal motifs
      KKXX or KXKXX, and does not pass the Golgi apparatus. Instead, it belongs to the
      rare group of viral glycoproteins in which the transmembrane domain (TMD) itself
      mediates direct ER retention. This is the first report relating TMD usage of an
      ER-resident transmembrane protein to its lateral membrane motility as a paradigm
      in cell biology. We propose that TMD usage for ER retention facilitates free and
      fast floating in ER-related membranes and between ER subdomains.

PMID- 20147516
TI  - Effect of inactivation method on the cross-protective immunity induced by whole
      'killed' influenza A viruses and commercial vaccine preparations.
AB  - We have recently shown that intranasal (i.n.) administration of gamma-irradiated
      A/PR/8 [A/Puerto Rico/8/34 (H1N1)] protects mice against lethal avian influenza
      A/Vietnam/1203/2004 (H5N1) and other heterosubtypic influenza A infections. Here,
      we used gamma-irradiated, formalin- and UV-inactivated A/PC [A/Port Chalmers/1/73
      (H3N2)] virus preparations and compared their ability to induce both homologous
      and heterosubtypic protective immunity. Our data show that, in contrast to i.n.
      vaccination with formalin- or UV-inactivated virus, or the present commercially
      available trivalent influenza vaccine, a single dose of gamma-ray-inactivated
      A/PC (gamma-A/PC) conferred significant protection in mice against both
      homologous and heterosubtypic virus challenges. A multiple immunization regime
      was required for formalin-inactivated virus preparations to induce protective
      immunity against a homotypic virus challenge, but did not induce influenza A
      strain cross-protective immunity. The highly immunogenic gamma-A/PC, but not
      formalin- or UV-inactivated A/PC, nor the currently available subvirion vaccine,
      elicited cytotoxic T-cell responses that are most likely responsible for the
      cross-protective and long-lasting immunity against highly lethal influenza A
      infections in mice. Finally, freeze-drying of gamma-A/PC did not affect the
      ability to induce cross-protective immunity.

PMID- 20147517
TI  - A novel hepatitis B virus (HBV) subgenotype D (D8) strain, resulting from
      recombination between genotypes D and E, is circulating in Niger along with HBV/E
      strains.
AB  - Niger is a west African country that is highly endemic for hepatitis B virus
      (HBV) infection. The seroprevalence for HBV surface antigen (HBsAg) is about 20%;
      however, there are no reports on the molecular epidemiology of HBV strains
      spreading in Niger. In the present study, HBV isolates from the sera of 58
      consecutive, asymptomatic, HBsAg-positive blood donors were characterized.
      Genotype affiliation was determined by amplification, sequencing and phylogenetic
      analysis of the preS1, polymerase/reverse transcriptase (RT/Pol) and precore
      (preC)/C regions. The first series of results revealed that different genomic
      fragments clustered with different genotypes on phylogenetic trees, suggesting
      recombination events. Twenty-four complete genomic sequences were obtained by
      amplification and sequencing of seven overlapping regions covering the whole
      genome, and were studied by extensive phylogenetic analysis. Among them, 20
      (83.3%) were classified unequivocally as genotype E (HBV/E). The remaining four
      (16.7%) clustered on a distinct branch within HBV/D with strong bootstrap and
      posterior probability values. Complete molecular characterization of these four
      strains was achieved by the Simplot program, bootscanning analysis and cloning
      experiments, and enabled us to identify an HBV/D-E recombinant that formed a new
      HBV/D subgenotype spreading in Niger, tentatively named D8. Moreover, 20 new
      complete HBV/E nucleotide sequences were determined that exhibited higher genetic
      variability than is generally described in Africa. One was found to be a
      recombinant containing HBV/D sequences in the preS2 and RT/Pol regions. Taken
      together, these data suggest that, in Niger, genetic variability of HBV strains
      is still evolving, probably reflecting ancient endemic HBV infection.

PMID- 20147518
TI  - Human endogenous retrovirus protein Rec interacts with the testicular zinc-finger
      protein and androgen receptor.
AB  - More than 2000 human endogenous retrovirus (HERV) sequences are present in the
      human genome, yet only a few are intact and able to produce proteins. The normal
      functions of these, if any, are unknown, but some HERV proteins have been
      implicated in cancers, in particular germ-cell cancers. For instance, it has been
      documented that (i) patients with germ-cell tumours frequently produce antibodies
      against HERV proteins; (ii) transgenic mice expressing HERV-K (HML-2) rec are
      prone to testicular carcinoma in situ; and (iii) Rec can bind and suppress a
      guardian of germline stem-cell pluripotency, the promyelocytic leukaemia zinc
      finger protein (PLZF). This study identified the PLZF-related testicular zinc
      finger protein (TZFP) as a binding partner of HERV-K (HML-2) Rec. Interactions
      occurred via the N- and C-terminal domains of Rec and the C-terminal DNA-binding
      zinc-finger domain of TZFP (aa 375-450). Not much is known about the function of
      TZFP. The protein is expressed predominantly in the testis, where it functions as
      a transcriptional repressor that is active during specific stages of
      spermatogenesis. The most intensely studied function of TZFP is that of a co
      repressor of the activated androgen receptor (AR). Here, it was shown that Rec
      can form a trimeric complex with TZFP and AR, and can relieve the TZFP-mediated
      repression of AR-induced transactivation. In addition, Rec was able to overcome
      the direct transcriptional repression by TZFP of the c-myc gene promoter in
      reporter assays. Thus, HERV-K (HML-2) Rec may function as an oncoprotein by de
      repressing oncogenic transcription factors such as AR.

PMID- 20147519
TI  - A novel role for the viral Rev protein in promoting resistance to superinfection
      by human immunodeficiency virus type 1.
AB  - At the cellular level, cells infected with human immunodeficiency virus type 1
      (HIV-1) exhibit immunity to a second infection by the virus that initiated the
      first infection or by related viruses [superinfection resistance (SIR)]. In the
      case of HIV infection, SIR was basically attributed to downregulation of the CD4
      receptors. We have recently reported on an interaction between HIV-1 Rev and
      integrase (IN) proteins, which results in inhibition of IN activity in vitro and
      integration of cDNA in HIV-1-infected cells. A novel function for the viral Rev
      protein in controlling integration of HIV cDNAs was thus proposed. The results of
      the present work suggest involvement of the inhibitory Rev in sustaining SIR. A
      single exposure to wild-type HIV-1 resulted in one to two integrations per cell.
      The number of integrated proviral cDNA copies remained at this low level even
      after double infection or superinfection. SIR was dependent on Rev expression by
      the strain used for the first infection and was eliminated by peptides that
      disrupt intracellular complex formation between IN and Rev. The same lack of
      resistance was observed in the absence of Rev, namely following first infection
      with a DeltaRev HIV strain. The involvement of Rev, expressed from either
      unintegrated or integrated viral cDNA, in promoting SIR was clearly demonstrated.
      We conclude that SIR involves Rev-dependent control of HIV cDNA integration.

PMID- 20147520
TI  - Murine norovirus-1 cell entry is mediated through a non-clathrin-, non-caveolae-,
      dynamin- and cholesterol-dependent pathway.
AB  - For many viruses, endocytosis and exposure to the low pH within acidic endosomes
      is essential for infection. It has previously been reported that feline
      calicivirus uses clathrin-mediated endocytosis for entry into mammalian cells.
      Here, we report that infection of RAW264.7 macrophages by the closely related
      murine norovirus-1 (MNV-1) does not require the clathrin pathway, as infection
      was not inhibited by expression of dominant-negative Eps15 or by knockdown of the
      adaptin-2 complex. Further, infection was not inhibited by reagents that raise
      endosomal pH. RAW264.7 macrophages were shown not to express caveolin, and
      flotillin depletion did not inhibit infection, suggesting that caveolae and the
      flotillin pathway are not required for cell entry. However, MNV-1 infection was
      inhibited by methyl-beta-cyclodextrin and the dynamin inhibitor, dynasore.
      Addition of these drugs to the cells after a period of virus internalization did
      not inhibit infection, suggesting the involvement of cholesterol-sensitive lipid
      rafts and dynamin in the entry mechanism. Macropinocytosis (MPC) was shown to be
      active in RAW264.7 macrophages (as indicated by uptake of dextran) and could be
      blocked by 5-(N-ethyl-N-isopropyl) amiloride (EIPA), which is reported to inhibit
      this pathway. However, infection was enhanced in the presence of EIPA. Similarly,
      actin disruption, which also inhibits MPC, resulted in enhanced infection. These
      results suggest that MPC could contribute to virus degradation or that inhibition
      of MPC could lead to the upregulation of other endocytic pathways of virus
      uptake.

PMID- 20147521
TI  - Colostral transmission of porcine circovirus 2 (PCV-2): reproduction of post
      weaning multisystemic wasting syndrome in pigs fed milk from PCV-2-infected sows
      with post-natal porcine parvovirus infection or immunostimulation.
AB  - Post-weaning multisystemic wasting syndrome (PMWS) was reproduced in pigs fed
      colostrum and milk from porcine circovirus 2 (PCV-2)-infected sows and infected
      post-natally with porcine parvovirus (PPV) or immunostimulated. Pregnant sows
      were inoculated intranasally with either PCV-2 (n=5) or PCV-2-free PK-15 cell
      lysates (control, n=10) 3 weeks before the expected farrowing date. Newborn
      piglets from five of the control sows were introduced to PCV-2-infected sows (n=6
      for each sow) and allowed to feed on the colostrum for 12 h and then given 15 ml
      milk five times a day for 7 days. Newborn piglets from the other five control
      sows were fed colostrum and milk from their own sows. After 7 days, two piglets
      from each group were randomly selected to confirm PCV-2 infection. Twenty-one
      pigs fed by PCV-2-infected sows were randomly divided into three groups and
      subjected to post-natal PPV infection (group 1), immunostimulation (group 2) or
      no post-natal treatment (group 3). Twenty-one pigs fed by uninfected sows were
      also randomly divided and subjected to post-natal PCV-2 and PPV infection (group
      4), post-natal PCV-2 infection (group 5) or no treatment (group 6, negative
      control). Body weight was significantly greater in group 6 than in groups 1, 2
      and 4 at 49, 52, 56, 59 and 63 days of age. The typical granulomatous
      inflammatory reaction and lymphoid depletion of PMWS was observed in the lymph
      nodes of groups 1, 2 and 4 at 63 days of age. Group 3 had significantly fewer PCV
      2-positive cells than groups 1, 2 and 4. In conclusion, PCV-2 shed from colostrum
      and milk is infectious and reproduces PMWS with post-natal PPV infection or
      immune stimulation.

PMID- 20147522
TI  - Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin
      dependent kinase 2 localization and cyclin E in vitamin D-mediated growth
      inhibition.
AB  - 1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), inhibits proliferation of a
      variety of cell types including adenocarcinoma of the prostate. We have
      previously shown that 1,25-(OH)(2)D(3) increases the stability of the cyclin
      dependent kinase inhibitor p27(KIP1), decreases cyclin-dependent kinase 2 (CDK2)
      activity, and promotes G(1) phase accumulation in human prostate cancer cells.
      These effects correlate with cytoplasmic relocalization of CDK2. In this study,
      we investigated the role of CDK2 cytoplasmic relocalization in the
      antiproliferative effects of 1,25-(OH)(2)D(3). CDK2 was found to be necessary for
      prostate cancer cell proliferation. Although induced by 1,25-(OH)(2)D(3), the
      cyclin-dependent kinase inhibitor p27(KIP1) was dispensable for 1,25-(OH)(2)D(3)
      mediated growth inhibition. Reduction in CDK2 activity by 1,25-(OH)(2)D(3) was
      associated with decreased T160 phosphorylation, a residue whose phosphorylation
      in the nucleus is essential for CDK2 activity. Ectopic expression of cyclin E was
      sufficient to overcome 1,25-(OH)(2)D(3)-mediated cytoplasmic mislocalization of
      CDK2 and all antiproliferative effects of 1,25-(OH)(2)D(3), yet endogenous levels
      of cyclin E or binding to CDK2 were not affected by 1,25-(OH)(2)D(3). Similarly,
      knockdown of the CDK2 substrate retinoblastoma, which causes cyclin E up
      regulation, resulted in resistance to 1,25-(OH)(2)D(3)-mediated growth
      inhibition. Human prostate cancer cells resistant to growth inhibition by 1,25
      (OH)(2)D(3) but retaining fully functional vitamin D receptors were developed.
      These cells did not exhibit 1,25-(OH)(2)D(3)-mediated cytoplasmic relocalization
      of CDK2. Targeting CDK2 to the nucleus of 1,25-(OH)(2)D(3)-sensitive cancer cells
      blocked G(1) accumulation and growth inhibition by 1,25-(OH)(2)D(3). These data
      establish central roles for CDK2 nuclear-cytoplasmic trafficking and cyclin E in
      the mechanism of 1,25-(OH)(2)D(3)-mediated growth inhibition in prostate cancer
      cells.

PMID- 20147523
TI  - Vasotocin/V2-type receptor/aquaporin axis exists in African lungfish kidney but
      is functional only in terrestrial condition.
AB  - The vasopressin/vasotocin (VT)-V2-type receptor (V2R)-aquaporin (AQP)-2 axis
      plays a pivotal role in renal water reabsorption in tetrapods. It is widely
      thought that this axis evolved with the emergence of the tetrapods, reflecting a
      requirement of water retention in terrestrial environment. Here we report that
      lungfish, the closest living relatives of tetrapods, already possess a system
      similar to the VT-V2R-AQP2 axis in the kidney, but the system is functional only
      in the terrestrial estivating condition. We cloned a novel AQP paralogous to
      AQP0. The water permeability of Xenopus oocytes was increased by injection with
      the AQP cRNA and was further facilitated by preincubation with cAMP. In the
      kidney of estivating lungfish, the AQP protein was localized on the apical plasma
      membrane of the late distal tubule and was colocalized with basolateral V2R. By
      contrast, we found only little expression of the AQP mRNA and protein in the
      kidney of lungfish in aquatic condition. The expression levels of mRNA and
      protein were dramatically increased during estivation and decreased again by
      reacclimation of estivating lungfish to water. The AQP mRNA levels positively
      correlated with the VT mRNA levels in the hypothalamus, suggesting that the AQP
      exerts tubular antidiuretic action under control of VT. Because the tetrapod
      AQP2/AQP5 lineage is considered to be evolved from duplication of an AQP0 gene,
      the paralogous AQP0 in the lungfish probably represents ancestral molecule for
      tetrapod AQP2.

PMID- 20147524
TI  - Disruption of the dopamine d2 receptor impairs insulin secretion and causes
      glucose intolerance.
AB  - The relationship between antidopaminergic drugs and glucose has not been
      extensively studied, even though chronic neuroleptic treatment causes
      hyperinsulinemia in normal subjects or is associated with diabetes in psychiatric
      patients. We sought to evaluate dopamine D2 receptor (D2R) participation in
      pancreatic function. Glucose homeostasis was studied in D2R knockout mice (Drd2(
      /-)) mice and in isolated islets from wild-type and Drd2(-/-) mice, using
      different pharmacological tools. Pancreas immunohistochemistry was performed.
      Drd2(-/-) male mice exhibited an impairment of insulin response to glucose and
      high fasting glucose levels and were glucose intolerant. Glucose intolerance
      resulted from a blunted insulin secretory response, rather than insulin
      resistance, as shown by glucose-stimulated insulin secretion tests (GSIS) in vivo
      and in vitro and by a conserved insulin tolerance test in vivo. On the other
      hand, short-term treatment with cabergoline, a dopamine agonist, resulted in
      glucose intolerance and decreased insulin response to glucose in wild-type but
      not in Drd2(-/-) mice; this effect was partially prevented by haloperidol, a D2R
      antagonist. In vitro results indicated that GSIS was impaired in islets from
      Drd2(-/-) mice and that only in wild-type islets did dopamine inhibit GSIS, an
      effect that was blocked by a D2R but not a D1R antagonist. Finally,
      immunohistochemistry showed a diminished pancreatic beta-cell mass in Drd2(-/-)
      mice and decreased beta-cell replication in 2-month-old Drd2(-/-) mice.
      Pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic
      inhibition throughout development may exert a gradual deteriorating effect on
      insulin homeostasis, so that eventually glucose intolerance develops.

PMID- 20147525
TI  - 1{alpha},25-Dihydroxyvitamin D3 inhibits growth of VCaP prostate cancer cells
      despite inducing the growth-promoting TMPRSS2:ERG gene fusion.
AB  - Vitamin D receptor (VDR) agonists have been shown to reduce the growth of several
      prostate cancer cell lines. However, the effects of VDR activation have not been
      examined in the presence of the recently identified androgen-regulated
      TMPRSS2:ERG gene fusions, which occur in a high percentage of prostate cancers
      and play a role in growth and invasiveness. In a previous microarray study, we
      found that VDR activation induces TMPRSS2 expression in LNCaP prostate cancer
      cells. Here we show that the natural VDR agonist 1alpha,25-dihydroxyvitamin D(3)
      and its synthetic analog EB1089 increase expression of TMPRSS2:ERG mRNA in VCaP
      prostate cancer cells; this results in increased ETS-related gene (ERG) protein
      expression and ERG activity as demonstrated by an increase in the ERG target gene
      CACNA1D. In VCaP cells, we were not able to prevent EB1089-mediated TMPRSS2:ERG
      induction with an androgen receptor antagonist, Casodex, although in LNCaP cells,
      as reported for some other common androgen receptor and VDR target genes, Casodex
      reduces EB1089-mediated induction of TMPRSS2. However, despite inducing the
      fusion gene, VDR agonists reduce VCaP cell growth and expression of the ERG
      target gene c-Myc, a critical factor in VDR-mediated growth inhibition. Thus, the
      beneficial effects of VDR agonist treatment override some of the negative effects
      of ERG induction, although others remain to be tested.

PMID- 20147526
TI  - The effect of dietary protein on intestinal calcium absorption in rats.
AB  - Increasing dietary protein intake in humans acutely increases urinary calcium.
      Isotopic absorption studies have indicated that, at least in the short term, this
      is primarily due to increased intestinal Ca absorption. To explore the mechanisms
      underlying dietary protein's effect on intestinal Ca absorption, female Sprague
      Dawley rats were fed a control (20%), low (5%), or high (40%) protein diet for 7
      d, and Ca balance was measured during d 4-7. On d 7, duodenal mucosa was
      harvested and brush border membrane vesicles (BBMVs) were prepared to evaluate Ca
      uptake. By d 7, urinary calcium was more than 2-fold higher in the 40% protein
      group compared with control (4.2 mg/d vs. 1.7 mg/d; P < 0.05). Rats consuming the
      40% protein diet both absorbed and retained more Ca compared with the 5% protein
      group (absorption: 48.5% vs. 34.1% and retention: 45.8% vs. 33.7%, respectively;
      P < 0.01). Ca uptake was increased in BBMVs prepared from rats consuming the high
      protein diet. Maximum velocity (V(max)) was higher in the BBMVs prepared from the
      high-protein group compared with those from the low-protein group (90 vs. 36 nmol
      Ca/mg protein x min, P < 0.001; 95% CI: 46-2486 and 14-55, respectively). The
      Michaelis Menten constant (K(m)) was unchanged (2.2 mm vs. 1.8 mm, respectively;
      P = 0.19). We conclude that in rats, as in humans, acute increases in protein
      intake result in hypercalciuria due to augmented intestinal Ca absorption. BBMV
      Ca uptake studies suggest that higher protein intake improves Ca absorption, at
      least in part, by increasing transcellular Ca uptake.

PMID- 20147527
TI  - Subcortical representation of non-Fourier image features.
AB  - A fundamental goal of visual neuroscience is to identify the neural pathways
      representing different image features. It is widely argued that the early stages
      of these pathways represent linear features of the visual scene and that the
      nonlinearities necessary to represent complex visual patterns are introduced
      later in cortex. We tested this by comparing the responses of subcortical and
      cortical neurons to interference patterns constructed by summing sinusoidal
      gratings. Although a linear mechanism can detect the component gratings, a
      nonlinear mechanism is required to detect an interference pattern resulting from
      their sum. Consistent with in vitro retinal ganglion cell recordings, we found
      that interference patterns are represented subcortically by cat LGN Y-cells, but
      not X-cells. Linear and nonlinear tuning properties of LGN Y-cells were then
      characterized and compared quantitatively with those of cortical area 18 neurons
      responsive to interference patterns. This comparison revealed a high degree of
      similarity between the two neural populations, including the following: (1) the
      representation of similar spatial frequencies in both their linear and nonlinear
      responses, (2) comparable orientation selectivity for the high spatial frequency
      carrier of interference patterns, and (3) the same difference in their temporal
      frequency selectivity for drifting gratings versus the envelope of interference
      patterns. The present findings demonstrate that the nonlinear subcortical Y-cell
      pathway represents complex visual patterns and likely underlies cortical
      responses to interference patterns. We suggest that linear and nonlinear
      mechanisms important for encoding visual scenes emerge in parallel through
      distinct pathways originating at the retina.

PMID- 20147528
TI  - Temporally diverse firing patterns in olfactory receptor neurons underlie
      spatiotemporal neural codes for odors.
AB  - Odorants are represented as spatiotemporal patterns of spikes in neurons of the
      antennal lobe (AL; insects) and olfactory bulb (OB; vertebrates). These response
      patterns have been thought to arise primarily from interactions within the AL/OB,
      an idea supported, in part, by the assumption that olfactory receptor neurons
      (ORNs) respond to odorants with simple firing patterns. However, activating the
      AL directly with simple pulses of current evoked responses in AL neurons that
      were much less diverse, complex, and enduring than responses elicited by
      odorants. Similarly, models of the AL driven by simplistic inputs generated
      relatively simple output. How then are dynamic neural codes for odors generated?
      Consistent with recent results from several other species, our recordings from
      locust ORNs showed a great diversity of temporal structure. Furthermore, we found
      that, viewed as a population, many response features of ORNs were remarkably
      similar to those observed within the AL. Using a set of computational models
      constrained by our electrophysiological recordings, we found that the temporal
      heterogeneity of responses of ORNs critically underlies the generation of
      spatiotemporal odor codes in the AL. A test then performed in vivo confirmed
      that, given temporally homogeneous input, the AL cannot create diverse
      spatiotemporal patterns on its own; however, given temporally heterogeneous
      input, the AL generated realistic firing patterns. Finally, given the temporally
      structured input provided by ORNs, we clarified several separate, additional
      contributions of the AL to olfactory information processing. Thus, our results
      demonstrate the origin and subsequent reformatting of spatiotemporal neural codes
      for odors.

PMID- 20147529
TI  - Interaction between facilitation and depression at a large CNS synapse reveals
      mechanisms of short-term plasticity.
AB  - The two fundamental forms of short-term plasticity, short-term depression and
      facilitation, coexist at most synapses, but little is known about their
      interaction. Here, we studied the interplay between short-term depression and
      facilitation at calyx of Held synapses. Stimulation at a "low" frequency of 10 or
      20 Hz, which is in the range of the spontaneous activity of these auditory
      neurons in vivo, induced synaptic depression. Surprisingly, an instantaneous
      increase of the stimulation frequency to 100 or 200 Hz following the low
      frequency train uncovered a robust facilitation of EPSCs relative to the
      predepressed amplitude level. This facilitation decayed rapidly ( approximately
      30 ms) and depended on presynaptic residual Ca(2+), but it was not caused by
      Ca(2+) current facilitation. To probe the release probability of the remaining
      readily releasable vesicles following the low-frequency train we made presynaptic
      Ca(2+) uncaging experiments in the predepressed state of the synapse. We found
      that low-frequency stimulation depletes the fast-releasable vesicle pool (FRP)
      down to approximately 40% of control and that the remaining FRP vesicles are
      released with approximately 2-fold slower release kinetics, indicating a hitherto
      unknown intrinsic heterogeneity among FRP vesicles. Thus, vesicles with an
      intrinsically lower release probability predominate after low frequency
      stimulation and undergo facilitation during the onset of subsequent high
      frequency trains. Facilitation in the predepressed state of the synapse might
      help to stabilize the amount of transmitter release at the onset of high
      frequency firing at these auditory synapses.

PMID- 20147530
TI  - Loss of retrograde endocannabinoid signaling and reduced adult neurogenesis in
      diacylglycerol lipase knock-out mice.
AB  - Endocannabinoids (eCBs) function as retrograde signaling molecules at synapses
      throughout the brain, regulate axonal growth and guidance during development, and
      drive adult neurogenesis. There remains a lack of genetic evidence as to the
      identity of the enzyme(s) responsible for the synthesis of eCBs in the brain.
      Diacylglycerol lipase-alpha (DAGLalpha) and -beta (DAGLbeta) synthesize 2
      arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain. However, their
      respective contribution to this and to eCB signaling has not been tested. In the
      present study, we show approximately 80% reductions in 2-AG levels in the brain
      and spinal cord in DAGLalpha(-/-) mice and a 50% reduction in the brain in
      DAGLbeta(-/-) mice. In contrast, DAGLbeta plays a more important role than
      DAGLalpha in regulating 2-AG levels in the liver, with a 90% reduction seen in
      DAGLbeta(-/-) mice. Levels of arachidonic acid decrease in parallel with 2-AG,
      suggesting that DAGL activity controls the steady-state levels of both lipids. In
      the hippocampus, the postsynaptic release of an eCB results in the transient
      suppression of GABA-mediated transmission at inhibitory synapses; we now show
      that this form of synaptic plasticity is completely lost in DAGLalpha(-/-)
      animals and relatively unaffected in DAGLbeta(-/-) animals. Finally, we show that
      the control of adult neurogenesis in the hippocampus and subventricular zone is
      compromised in the DAGLalpha(-/-) and/or DAGLbeta(-/-) mice. These findings
      provide the first evidence that DAGLalpha is the major biosynthetic enzyme for 2
      AG in the nervous system and reveal an essential role for this enzyme in
      regulating retrograde synaptic plasticity and adult neurogenesis.

PMID- 20147531
TI  - CD200R1 agonist attenuates mechanisms of chronic disease in a murine model of
      multiple sclerosis.
AB  - To assess the effects and mechanisms of a CD200R1 agonist administered during the
      progressive stage of a multiple sclerosis model, we administered CD200R1 agonist
      (CD200Fc) or control IgG2a during the chronic phase of disease (days 10-30) in
      mice with experimental autoimmune encephalomyelitis (EAE), induced using myelin
      oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) peptide. We found that
      administration of CD200Fc during the chronic stages of EAE reduced disease
      severity, demyelination, and axonal damage, through the modulation of several key
      disease mechanisms. CD200Fc treatment suppressed macrophage and microglial
      accumulation within the CNS, in part through downregulation of adhesion molecules
      VLA-4 and LFA-1, which are necessary for macrophage migration. Additionally,
      expression of activation markers MHC-II and CD80 and production of
      proinflammatory cytokines IL-6, tumor necrosis factor-alpha, and nitric oxide by
      CD11b(+) cells were decreased in both the spleen and CNS in CD200Fc-treated
      animals. Antigen-presenting cell function in the spleen and CNS was suppressed in
      CD200Fc-treated mice, but there were no significant alterations on T cell
      activation or phenotype. CD200Fc increased apoptosis of CD11b(+) cells but not
      astrocytes. In contrast, addition of CD200Fc treatment protected oligodendrocytes
      from apoptosis in vitro and in vivo. Our results demonstrate that CD200R1
      agonists modulate both myeloid- and non-myeloid-related mechanisms of chronic
      disease in the EAE model and may be effective in the treatment of progressive
      multiple sclerosis and other neurodegenerative diseases.

PMID- 20147532
TI  - Perisomatic voltage-gated sodium channels actively maintain linear synaptic
      integration in principal neurons of the medial superior olive.
AB  - Principal neurons of the medial superior olive (MSO) compute azimuthal sound
      location by integrating phase-locked inputs from each ear. While previous
      experimental and modeling studies have proposed that voltage-gated sodium
      channels (VGSCs) play an important role in synaptic integration in the MSO, these
      studies appear at odds with the unusually weak active backpropagation of action
      potentials into the soma and dendrites. To understand the spatial localization
      and biophysical properties of VGSCs, we isolated sodium currents in MSO principal
      neurons in gerbil brainstem slices. Nucleated and cell-attached patches revealed
      that VGSC density at the soma is comparable to that of many other neuron types,
      but channel expression is largely absent from the dendrites. Further, while
      somatic VGSCs activated with conventional voltage dependence (V(1/2) = -30 mV),
      they exhibited an unusually negative range of steady-state inactivation (V(1/2) =
      -77 mV), leaving approximately 92% of VGSCs inactivated at the resting potential
      (approximately -58 mV). In current-clamp experiments, non-inactivated VGSCs were
      sufficient to amplify subthreshold EPSPs near action potential threshold,
      counterbalancing the suppression of EPSP peaks by low voltage-activated potassium
      channels. EPSP amplification was restricted to the perisomatic region of the
      neuron, and relatively insensitive to preceding inhibition. Finally,
      computational modeling showed that the exclusion of VGSCs from the dendrites
      equalizes somatic EPSP amplification across synaptic locations and lowered the
      threshold for bilateral versus unilateral excitatory synaptic inputs. Together,
      these findings suggest that the pattern of sodium channel expression in MSO
      neurons contributes to these neurons' selectivity for coincident binaural inputs.

PMID- 20147533
TI  - The developmental stage of dentate granule cells dictates their contribution to
      seizure-induced plasticity.
AB  - Dentate granule cell (DGC) neurogenesis persists throughout life in the
      hippocampal dentate gyrus. In rodent temporal lobe epilepsy models, status
      epilepticus (SE) stimulates neurogenesis, but many newborn DGCs integrate
      aberrantly and are hyperexcitable, whereas others may integrate normally and
      restore inhibition. The overall influence of altered neurogenesis on
      epileptogenesis is therefore unclear. To better understand the role DGC
      neurogenesis plays in seizure-induced plasticity, we injected retroviral (RV)
      reporters to label dividing DGC progenitors at specific times before or after SE,
      or used x-irradiation to suppress neurogenesis. RV injections 7 weeks before SE
      to mark DGCs that had matured by the time of SE labeled cells with normal
      placement and morphology 4 weeks after SE. RV injections 2 or 4 weeks before
      seizure induction to label cells still developing during SE revealed normally
      located DGCs exhibiting hilar basal dendrites and mossy fiber sprouting (MFS)
      when observed 4 weeks after SE. Cells labeled by injecting RV after SE displayed
      hilar basal dendrites and ectopic migration, but not sprouting, at 28 d after SE;
      when examined 10 weeks after SE, however, these cells showed robust MFS.
      Eliminating cohorts of newborn DGCs by focal brain irradiation at specific times
      before or after SE decreased MFS or hilar ectopic DGCs, supporting the RV
      labeling results. These findings indicate that developing DGCs exhibit maturation
      dependent vulnerability to SE, indicating that abnormal DGC plasticity derives
      exclusively from aberrantly developing DGCs. Treatments that restore normal DGC
      development after epileptogenic insults may therefore ameliorate epileptogenic
      network dysfunction and associated morbidities.

PMID- 20147534
TI  - Integration of vibrotactile signals for whisker-related perception in rats is
      governed by short time constants: comparison of neurometric and psychometric
      detection performance.
AB  - Rats explore environments by sweeping their whiskers across objects and surfaces.
      Both sensor movement and repetitive sweeping typical for this behavior require
      that vibrotactile signals are integrated over time. While temporal integration
      properties of neurons along the whisker somatosensory pathway have been studied
      extensively, the consequences for behavior are unknown. Here, we investigate the
      ability of head-fixed rats to integrate information over time for the detection
      of near-threshold pulsatile deflection sequences applied to a single whisker.
      Psychometric detection performance was assessed with whisker stimuli composed of
      different numbers of pulses (1-31) delivered at varying frequencies (10, 20, 100
      Hz). Detection performance indeed improved with increasing number and frequency
      of pulses, albeit this improvement was much lower than predicted by probabilistic
      combination, suggesting highly sublinear integration of pulses. This behavioral
      observation was reflected in the firing properties of concomitantly recorded
      barrel cortex neurons, which showed substantial response adaptation to repetitive
      whisker deflection. To estimate the integration time with which barrel cortex
      neuronal activity must be read out to match behavior, we constructed a model
      monitoring spiking activity of simulated neuronal pools, where spike trains were
      channeled through a leaky integrator with exponential decay. Detection was
      accomplished by simple threshold crossings. This simple model gave an excellent
      match of neurometric and psychometric data at surprisingly small time constants
      tau of 5-8 ms, thus limiting integration largely to <25 ms. This result carries
      important implications regarding sensory processing for whisker-mediated
      perception.

PMID- 20147535
TI  - Cortical mechanisms for the segregation and representation of acoustic textures.
AB  - Auditory object analysis requires two fundamental perceptual processes: the
      definition of the boundaries between objects, and the abstraction and maintenance
      of an object's characteristic features. Although it is intuitive to assume that
      the detection of the discontinuities at an object's boundaries precedes the
      subsequent precise representation of the object, the specific underlying cortical
      mechanisms for segregating and representing auditory objects within the auditory
      scene are unknown. We investigated the cortical bases of these two processes for
      one type of auditory object, an "acoustic texture," composed of multiple
      frequency-modulated ramps. In these stimuli, we independently manipulated the
      statistical rules governing (1) the frequency-time space within individual
      textures (comprising ramps with a given spectrotemporal coherence) and (2) the
      boundaries between textures (adjacent textures with different spectrotemporal
      coherences). Using functional magnetic resonance imaging, we show mechanisms
      defining boundaries between textures with different coherences in primary and
      association auditory cortices, whereas texture coherence is represented only in
      association cortex. Furthermore, participants' superior detection of boundaries
      across which texture coherence increased (as opposed to decreased) was reflected
      in a greater neural response in auditory association cortex at these boundaries.
      The results suggest a hierarchical mechanism for processing acoustic textures
      that is relevant to auditory object analysis: boundaries between objects are
      first detected as a change in statistical rules over frequency-time space, before
      a representation that corresponds to the characteristics of the perceived object
      is formed.

PMID- 20147536
TI  - Complement component c1q mediates mitochondria-driven oxidative stress in
      neonatal hypoxic-ischemic brain injury.
AB  - Hypoxic-ischemic (HI) brain injury in infants is a leading cause of lifelong
      disability. We report a novel pathway mediating oxidative brain injury after
      hypoxia-ischemia in which C1q plays a central role. Neonatal mice incapable of
      classical or terminal complement activation because of C1q or C6 deficiency or
      pharmacologically inhibited assembly of membrane attack complex were subjected to
      hypoxia-ischemia. Only C1q(-/-) mice exhibited neuroprotection coupled with
      attenuated oxidative brain injury. This was associated with reduced production of
      reactive oxygen species (ROS) in C1q(-/-) brain mitochondria and preserved
      activity of the respiratory chain. Compared with C1q(+/+) neurons, cortical C1q(
      /-) neurons exhibited resistance to oxygen-glucose deprivation. However,
      postischemic exposure to exogenous C1q increased both mitochondrial ROS
      production and mortality of C1q(-/-) neurons. This C1q toxicity was abolished by
      coexposure to antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2
      carboxylic acid). Thus, the C1q component of complement, accelerating
      mitochondrial ROS emission, exacerbates oxidative injury in the developing HI
      brain. The terminal complement complex is activated in the HI neonatal brain but
      appeared to be nonpathogenic. These findings have important implications for
      design of the proper therapeutic interventions against HI neonatal brain injury
      by highlighting a pathogenic priority of C1q-mediated mitochondrial oxidative
      stress over the C1q deposition-triggered terminal complement activation.

PMID- 20147537
TI  - CSF biomarkers in prediction of cerebral and clinical change in mild cognitive
      impairment and Alzheimer's disease.
AB  - Brain atrophy and altered CSF levels of amyloid beta (Abeta(42)) and the
      microtubule-associated protein tau are potent biomarkers of Alzheimer's disease
      (AD)-related pathology. However, the relationship between CSF biomarkers and
      brain morphometry is poorly understood. Thus, we addressed the following
      questions. (1) Can CSF biomarker levels explain the morphometric differences
      between normal controls (NC) and patients with mild cognitive impairment (MCI) or
      AD? (2) How are CSF biomarkers related to atrophy across the brain? (3) How
      closely are CSF biomarkers and morphometry related to clinical change [clinical
      dementia rating sum of boxes (CDR-sb)]? Three hundred seventy participants (105
      NC, 175 MCI, 90 AD) from the Alzheimer's Disease Neuroimaging Initiative were
      studied, of whom 309 were followed for 1 year and 176 for 2 years. Analyses were
      performed across the entire cortical surface, as well as for 30 cortical and
      subcortical regions of interest. Results showed that CSF biomarker levels could
      not account for group differences in brain morphometry at baseline but that CSF
      biomarker levels showed moderate relationships to longitudinal atrophy rates in
      numerous brain areas, not restricted to medial temporal structures. Baseline
      morphometry was at least as predictive of atrophy as were CSF biomarkers. Even
      MCI patients with levels of Abeta(42) comparable with controls and of p-tau lower
      than controls showed more atrophy than the controls. Morphometry predicted change
      in CDR-sb better than did CSF biomarkers. These results indicate that
      morphometric changes in MCI and AD are not secondary to CSF biomarker changes and
      that the two types of biomarkers yield complementary information.

PMID- 20147538
TI  - Neural representation of natural images in visual area V2.
AB  - Area V2 is a major visual processing stage in mammalian visual cortex, but little
      is currently known about how V2 encodes information during natural vision. To
      determine how V2 represents natural images, we used a novel nonlinear system
      identification approach to obtain quantitative estimates of spatial tuning across
      a large sample of V2 neurons. We compared these tuning estimates with those
      obtained in area V1, in which the neural code is relatively well understood. We
      find two subpopulations of neurons in V2. Approximately one-half of the V2
      neurons have tuning that is similar to V1. The other half of the V2 neurons are
      selective for complex features such as those that occur in natural scenes. These
      neurons are distinguished from V1 neurons mainly by the presence of stronger
      suppressive tuning. Selectivity in these neurons therefore reflects a balance
      between excitatory and suppressive tuning for specific features. These results
      provide a new perspective on how complex shape selectivity arises, emphasizing
      the role of suppressive tuning in determining stimulus selectivity in higher
      visual cortex.

PMID- 20147539
TI  - Neuroligin-1 deletion results in impaired spatial memory and increased repetitive
      behavior.
AB  - Neuroligins (NLs) are a family of neural cell-adhesion molecules that are
      involved in excitatory/inhibitory synapse specification. Multiple members of the
      NL family (including NL1) and their binding partners have been linked to cases of
      human autism and mental retardation. We have now characterized NL1-deficient mice
      in autism- and mental retardation-relevant behavioral tasks. NL1 knock-out (KO)
      mice display deficits in spatial learning and memory that correlate with impaired
      hippocampal long-term potentiation. In addition, NL1 KO mice exhibit a dramatic
      increase in repetitive, stereotyped grooming behavior, a potential autism
      relevant abnormality. This repetitive grooming abnormality in NL1 KO mice is
      associated with a reduced NMDA/AMPA ratio at corticostriatal synapses.
      Interestingly, we further demonstrate that the increased repetitive grooming
      phenotype can be rescued in adult mice by administration of the NMDA receptor
      partial coagonist d-cycloserine. Broadly, these data are consistent with a role
      of synaptic cell-adhesion molecules in general, and NL1 in particular, in autism
      and implicate reduced excitatory synaptic transmission as a potential mechanism
      and treatment target for repetitive behavioral abnormalities.

PMID- 20147540
TI  - Mental hoop diaries: emotional memories of a college basketball game in rival
      fans.
AB  - The rivalry between the men's basketball teams of Duke University and the
      University of North Carolina-Chapel Hill (UNC) is one of the most storied
      traditions in college sports. A subculture of students at each university form
      social bonds with fellow fans, develop expertise in college basketball rules,
      team statistics, and individual players, and self-identify as a member of a fan
      group. The present study capitalized on the high personal investment of these
      fans and the strong affective tenor of a Duke-UNC basketball game to examine the
      neural correlates of emotional memory retrieval for a complex sporting event.
      Male fans watched a competitive, archived game in a social setting. During a
      subsequent functional magnetic resonance imaging session, participants viewed
      video clips depicting individual plays of the game that ended with the ball being
      released toward the basket. For each play, participants recalled whether or not
      the shot went into the basket. Hemodynamic signal changes time locked to correct
      memory decisions were analyzed as a function of emotional intensity and valence,
      according to the fan's perspective. Results showed intensity-modulated retrieval
      activity in midline cortical structures, sensorimotor cortex, the striatum, and
      the medial temporal lobe, including the amygdala. Positively valent memories
      specifically recruited processing in dorsal frontoparietal regions, and
      additional activity in the insula and medial temporal lobe for positively valent
      shots recalled with high confidence. This novel paradigm reveals how brain
      regions implicated in emotion, memory retrieval, visuomotor imagery, and social
      cognition contribute to the recollection of specific plays in the mind of a
      sports fan.

PMID- 20147541
TI  - GRK2: a novel cell-specific regulator of severity and duration of inflammatory
      pain.
AB  - Chronic pain associated with inflammation is a common clinical problem, and the
      underlying mechanisms have only begun to be unraveled. GRK2 regulates cellular
      signaling by promoting G-protein-coupled receptor (GPCR) desensitization and
      direct interaction with downstream kinases including p38. The aim of this study
      was to determine the contribution of GRK2 to regulation of inflammatory pain and
      to unravel the underlying mechanism. GRK2(+/-) mice with an approximately 50%
      reduction in GRK2 developed increased and markedly prolonged thermal hyperalgesia
      and mechanical allodynia after carrageenan-induced paw inflammation or after
      intraplantar injection of the GPCR-binding chemokine CCL3. The effect of reduced
      GRK2 in specific cells was investigated using Cre-Lox technology. Carrageenan- or
      CCL3-induced hyperalgesia was increased but not prolonged in mice with decreased
      GRK2 only in Na(v)1.8 nociceptors. In vitro, reduced neuronal GRK2 enhanced CCL3
      induced TRPV1 sensitization. In vivo, CCL3-induced acute hyperalgesia in GRK2(+/
      ) mice was mediated via TRPV1. Reduced GRK2 in microglia/monocytes only was
      required and sufficient to transform acute carrageenan- or CCL3-induced
      hyperalgesia into chronic hyperalgesia. Chronic hyperalgesia in GRK2(+/-) mice
      was associated with ongoing microglial activation and increased phospho-p38 and
      tumor necrosis factor alpha (TNF-alpha) in the spinal cord. Inhibition of spinal
      cord microglial, p38, or TNF-alpha activity by intrathecal administration of
      specific inhibitors reversed ongoing hyperalgesia in GRK2(+/-) mice.
      Microglia/macrophage GRK2 expression was reduced in the lumbar ipsilateral spinal
      cord during neuropathic pain, underlining the pathophysiological relevance of
      microglial GRK2. Thus, we identified completely novel cell-specific roles of GRK2
      in regulating acute and chronic inflammatory hyperalgesia.

PMID- 20147542
TI  - Cell type-specific control of neuronal responsiveness by gamma-band oscillatory
      inhibition.
AB  - Neocortical networks are composed of diverse populations of cells that differ in
      their chemical content, electrophysiological characteristics, and connectivity.
      Gamma-frequency oscillatory activity of inhibitory subnetworks has been
      hypothesized to regulate information processing in the cortex as a whole.
      Inhibitory neurons in these subnetworks synchronize their firing and selectively
      innervate the perisomatic compartments of their target neurons, generating both
      tonic and rapidly fluctuating inhibition. How do different types of cortical
      neurons respond to changes in the level and structure of perisomatic inhibition?
      What accounts for response heterogeneity between cell types, and are these
      response properties fixed or flexible? To answer these questions, we use in vitro
      whole-cell recording and dynamic-clamp somatic current injection to study six
      distinct types of cortical neurons. We demonstrate that different types of
      neurons systematically vary in their receptiveness to fast changes in the
      structure of inhibition and the range over which changes in inhibitory tone
      affect their output. Using simple neuron models and model neuron hybrids (dynamic
      clamp), we determine which intrinsic differences between cell types lead to these
      variations in receptiveness. These results suggest important differences in the
      way cell types are affected by gamma-frequency inhibition, which may have
      important circuit level implications. Although intrinsic differences observed in
      vitro are useful for the elucidation of basic cellular properties and differences
      between cell types, we also investigate how the integrative properties of neurons
      are likely to be rapidly modulated in the context of active networks in vivo.

PMID- 20147543
TI  - Endocannabinoid signaling mediates psychomotor activation by adenosine A2A
      antagonists.
AB  - Adenosine A(2A) receptor antagonists are psychomotor stimulants that also hold
      therapeutic promise for movement disorders. However, the molecular mechanisms
      underlying their stimulant properties are not well understood. Here, we show that
      the robust increase in locomotor activity induced by an A(2A) antagonist in vivo
      is greatly attenuated by antagonizing cannabinoid CB(1) receptor signaling or by
      administration to CB(1)(-/-) mice. To determine the locus of increased
      endocannabinoid signaling, we measured the amount of anandamide [AEA (N
      arachidonoylethanolamine)] and 2-arachidonoylglycerol (2-AG) in brain tissue from
      striatum and cortex. We find that 2-AG is selectively increased in striatum after
      acute blockade of A(2A) receptors, which are highly expressed by striatal
      indirect-pathway medium spiny neurons (MSNs). Using targeted whole-cell
      recordings from direct- and indirect-pathway MSNs, we demonstrate that A(2A)
      receptor antagonists potentiate 2-AG release and induction of long-term
      depression at indirect-pathway MSNs, but not direct-pathway MSNs. Together, these
      data outline a molecular mechanism by which A(2A) antagonists reduce excitatory
      synaptic drive on the indirect pathway through CB(1) receptor signaling, thus
      leading to increased psychomotor activation.

PMID- 20147545
TI  - Reevaluation of neurodegeneration in lurcher mice: constitutive ion fluxes cause
      cell death with, not by, autophagy.
AB  - The lurcher (Lc) mice have served as a valuable model for neurodegeneration for
      decades. Although the responsible mutation was identified in genes encoding
      delta2 glutamate receptors (GluD2s), which are predominantly expressed in
      cerebellar Purkinje cells, how the mutant receptor (GluD2(Lc)) triggers cell
      death has remained elusive. Here, taking advantage of recent knowledge about the
      domain structure of GluD2, we reinvestigated Lc-mediated cell death, focusing on
      the "autophagic cell death" hypothesis. Although autophagy and cell death were
      induced by the expression of GluD2(Lc) in heterologous cells and cultured
      neurons, they were blocked by the introduction of mutations in the channel pore
      domain of GluD2(Lc) or by removal of extracellular Na(+). In addition, although
      GluD2(Lc) is reported to directly activate autophagy, mutant channels that are
      not associated with n-PIST (neuronal isoform of protein-interacting specifically
      with TC10)-Beclin1 still caused autophagy and cell death. Furthermore, cells
      expressing GluD2(Lc) showed decreased ATP levels and increased AMP-activated
      protein kinase (AMPK) activities in a manner dependent on extracellular Na(+).
      Thus, constitutive currents were likely necessary and sufficient to induce
      autophagy via AMPK activation, regardless of the n-PIST-Beclin1 pathway in vitro.
      Interestingly, the expression of dominant-negative AMPK suppressed GluD2(Lc)
      induced autophagy but did not prevent cell death in heterologous cells.
      Similarly, the disruption of Atg5, a gene crucial for autophagy, did not prevent
      but rather aggravated Purkinje-cell death in Lc mice. Furthermore, calpains were
      specifically activated in Lc Purkinje cells. Together, these results suggest that
      Lc-mediated cell death was not caused by autophagy but necrosis with autophagic
      features both in vivo and in vitro.

PMID- 20147546
TI  - Attention differentially modulates similar neuronal responses evoked by varying
      contrast and direction stimuli in area MT.
AB  - The effects of attention on the responses of visual neurons have been described
      as a scaling or additive modulation independent of stimulus features and
      contrast, or as a contrast-dependent modulation. We explored these alternatives
      by recording neuronal responses in macaque area MT to moving stimuli that evoked
      similar firing rates but varied in contrast and direction. We presented two
      identical pairs of stimuli, one inside the neurons' receptive field and the other
      outside, in the opposite hemifield. One stimulus of each pair always had high
      contrast and moved in the recorded cell's antipreferred direction (AP pattern),
      while the other (test pattern) could either move in the cell's preferred
      direction and vary in contrast, or have the same contrast as the AP pattern and
      vary in direction. For different stimulus pairs evoking similar responses,
      switching attention between the two AP patterns, or directing attention from a
      fixation spot to the AP pattern inside or outside the receptive field, produced a
      stronger suppression of responses to varying contrast pairs, reaching a maximum (
      approximately 20%) at intermediate contrast. For invariable contrast pairs,
      switching attention from the fixation spot to the AP pattern produced a
      modulation that ranged from 10% suppression when the test pattern moved in the
      cells preferred direction to 14% enhancement when it moved in a direction 90
      degrees away from that direction. Our results are incompatible with a scaling or
      additive modulation of MT neurons' response by attention, but support models
      where spatial and feature-based attention modulate input signals into the area
      normalization circuit.

PMID- 20147544
TI  - Common origins of hippocampal Ivy and nitric oxide synthase expressing
      neurogliaform cells.
AB  - GABAergic interneurons critically regulate cortical computation through exquisite
      spatiotemporal control over excitatory networks. Precision of this inhibitory
      control requires a remarkable diversity within interneuron populations that is
      largely specified during embryogenesis. Although interneurons expressing the
      neuronal isoform of nitric oxide synthase (nNOS) constitute the largest
      hippocampal interneuron cohort their origin and specification remain unknown.
      Thus, as neurogliaform cells (NGC) and Ivy cells (IvC) represent the main nNOS(+)
      interneurons, we investigated their developmental origins. Although considered
      distinct interneuron subtypes, NGCs and IvCs exhibited similar neurochemical and
      electrophysiological signatures, including NPY expression and late spiking.
      Moreover, lineage analyses, including loss-of-function experiments and inducible
      fate-mapping, indicated that nNOS(+) IvCs and NGCs are both derived from medial
      ganglionic eminence (MGE) progenitors under control of the transcription factor
      Nkx2-1. Surprisingly, a subset of NGCs lacking nNOS arises from caudal ganglionic
      eminence (CGE) progenitors. Thus, while nNOS(+) NGCs and IvCs arise from MGE
      progenitors, a CGE origin distinguishes a discrete population of nNOS(-) NGCs.

PMID- 20147547
TI  - VGLUT3 (vesicular glutamate transporter type 3) contribution to the regulation of
      serotonergic transmission and anxiety.
AB  - Three different subtypes of H(+)-dependent carriers (named VGLUT1-3) concentrate
      glutamate into synaptic vesicles before its exocytotic release. Neurons using
      other neurotransmitter than glutamate (such as cholinergic striatal interneurons
      and 5-HT neurons) express VGLUT3. It was recently reported that VGLUT3 increases
      acetylcholine vesicular filling, thereby, stimulating cholinergic transmission.
      This new regulatory mechanism is herein designated as vesicular-filling synergy
      (or vesicular synergy). In the present report, we found that deletion of VGLUT3
      increased several anxiety-related behaviors in adult and in newborn mice as early
      as 8 d after birth. This precocious involvement of a vesicular glutamate
      transporter in anxiety led us to examine the underlying functional implications
      of VGLUT3 in 5-HT neurons. On one hand, VGLUT3 deletion caused a significant
      decrease of 5-HT(1A)-mediated neurotransmission in raphe nuclei. On the other
      hand, VGLUT3 positively modulated 5-HT transmission of a specific subset of 5-HT
      terminals from the hippocampus and the cerebral cortex. VGLUT3- and VMAT2
      positive serotonergic fibers show little or no 5-HT reuptake transporter. These
      results unravel the existence of a novel subset of 5-HT terminals in limbic areas
      that might play a crucial role in anxiety-like behaviors. In summary, VGLUT3
      accelerates 5-HT transmission at the level of specific 5-HT terminals and can
      exert an inhibitory control at the raphe level. Furthermore, our results suggest
      that the loss of VGLUT3 expression leads to anxiety-associated behaviors and
      should be considered as a potential new target for the treatment of this
      disorder.

PMID- 20147548
TI  - Serotonin modulates fast-spiking interneuron and synchronous activity in the rat
      prefrontal cortex through 5-HT1A and 5-HT2A receptors.
AB  - Alterations of the serotonergic system in the prefrontal cortex (PFC) are
      implicated in psychiatric disorders such as schizophrenia and depression.
      Although abnormal synchronous activity is observed in the PFC of these patients,
      little is known about the role of serotonin (5-HT) in cortical synchrony. We
      found that 5-HT, released by electrical stimulation of the dorsal raphe nucleus
      (DRN) in anesthetized rats, regulates the frequency and the amplitude of slow (<2
      Hz) waves in the PFC via 5-HT(2A) receptors (5-HT(2A)Rs). 5-HT also modulates
      prefrontal gamma (30-80 Hz) rhythms through both 5-HT(1A)Rs and 5-HT(2A)Rs, but
      not 5-HT(2C)Rs, inducing an overall decrease in the amplitude of gamma
      oscillations. Because fast-spiking interneurons (FSi) are involved in the
      generation of gamma waves, we examined serotonergic modulation of FSi activity in
      vivo. Most FSi are inhibited by serotonin through 5-HT(1A)Rs, while a minority is
      activated by 5-HT(2A)Rs, and not 5-HT(2C)Rs. In situ hybridization histochemistry
      confirmed that distinct populations of FSi in the PFC express 5-HT(1A)Rs and 5
      HT(2A)Rs, and that the number of FSi expressing 5-HT(2C)Rs is negligible. We
      conclude that 5-HT exerts a potent control on slow and gamma oscillations in the
      PFC. On the one hand, it shapes the frequency and amplitude of slow waves through
      5-HT(2A)Rs. On the other hand, it finely tunes the amplitude of gamma
      oscillations through 5-HT(2A)R- and 5-HT(1A)R-expressing FSi, although it
      primarily downregulates gamma waves via the latter population. These results may
      provide insight into impaired serotonergic control of network activity in
      psychiatric illnesses such as schizophrenia and depression.

PMID- 20147549
TI  - Distinct roles of GABAergic interneurons in the regulation of striatal output
      pathways.
AB  - Striatal GABAergic microcircuits are critical for motor function, yet their
      properties remain enigmatic due to difficulties in targeting striatal
      interneurons for electrophysiological analysis. Here, we use Lhx6-GFP transgenic
      mice to identify GABAergic interneurons and investigate their regulation of
      striatal direct- and indirect-pathway medium spiny neurons (MSNs). We find that
      the two major interneuron populations, persistent low-threshold spiking (PLTS)
      and fast spiking (FS) interneurons, differ substantially in their excitatory
      inputs and inhibitory outputs. Excitatory synaptic currents recorded from PLTS
      interneurons are characterized by a small, nonrectifying AMPA receptor-mediated
      component and a NMDA receptor-mediated component. In contrast, glutamatergic
      synaptic currents in FS interneurons have a large, strongly rectifying AMPA
      receptor-mediated component, but no detectable NMDA receptor-mediated responses.
      Consistent with their axonal morphology, the output of individual PLTS
      interneurons is relatively weak and sparse, whereas FS interneurons are robustly
      connected to MSNs and other FS interneurons and appear to mediate the bulk of
      feedforward inhibition. Synaptic depression of FS outputs is relatively
      insensitive to firing frequency, and dynamic-clamp experiments reveal that these
      short-term dynamics enable feedforward inhibition to remain efficacious across a
      broad frequency range. Surprisingly, we find that FS interneurons preferentially
      target direct-pathway MSNs over indirect-pathway MSNs, suggesting a potential
      mechanism for rapid pathway-specific regulation of striatal output pathways.

PMID- 20147551
TI  - Detection of low salience whisker stimuli requires synergy of tectal and thalamic
      sensory relays.
AB  - Detection of a sensory stimulus depends on its psychophysical saliency; the
      higher the saliency, the easier the detection. But it is not known whether
      sensory relay nuclei differ in their ability to detect low salient whisker
      stimuli. We found that reversible lesions of either the somatosensory thalamus or
      superior colliculus blocked detection of a low salience whisker conditioned
      stimulus (WCS) in an active avoidance task, without affecting detection of a high
      salience WCS. Thus, thalamic and tectal sensory relays work synergistically to
      detect low salient stimuli during avoidance behavior, but are redundant during
      detection of highly salient stimuli. We also recorded electrophysiological
      responses evoked by high and low salience stimuli in the superior colliculus and
      barrel cortex of freely behaving animals during active exploration, awake
      immobility, and sensory detection in the active avoidance task. Field potential
      (FP) responses evoked in barrel cortex and superior colliculus by high intensity
      stimuli are larger and adapt more to frequency than those evoked by low-intensity
      stimuli. FP responses are also more suppressed and adapt less during active
      exploration, and become further suppressed in barrel cortex during successful
      detection of either high or low salient stimuli in the active avoidance task. In
      addition, unit recordings revealed that firing rate increases in superior
      colliculus during active exploration and especially during successful detection
      of either high or low salient stimuli in the active avoidance task. We conclude
      that detection of low salient stimuli is achieved by a sparse neural code
      distributed through multiple sensory relays.

PMID- 20147550
TI  - Ecto-5'-nucleotidase (CD73) inhibits nociception by hydrolyzing AMP to adenosine
      in nociceptive circuits.
AB  - Ecto-5'-nucleotidase (NT5E, CD73) is a membrane-anchored protein that hydrolyzes
      extracellular adenosine 5'-monophosphate (AMP) to adenosine in diverse tissues
      but has not been directly studied in nociceptive neurons. We found that NT5E was
      located on peptidergic and nonpeptidergic nociceptive neurons in dorsal root
      ganglia (DRG) and on axon terminals in lamina II (the substantia gelatinosa) of
      spinal cord. NT5E was also located on epidermal keratinocytes, cells of the
      dermis, and on nociceptive axon terminals in the epidermis. Following nerve
      injury, NT5E protein and AMP histochemical staining were coordinately reduced in
      lamina II. In addition, AMP hydrolytic activity was reduced in DRG neurons and
      spinal cord of Nt5e(-/-) mice. The antinociceptive effects of AMP, when combined
      with the adenosine kinase inhibitor 5-iodotubericidin, were reduced by
      approximately 50% in Nt5e(-/-) mice and were eliminated in Adenosine A(1)
      receptor (A(1)R, Adora1) knock-out mice. Additionally, Nt5e(-/-) mice displayed
      enhanced sensitivity in the tail immersion assay, in the complete Freund's
      adjuvant model of inflammatory pain and in the spared nerve injury model of
      neuropathic pain. Collectively, our data indicate that the ectonucleotidase NT5E
      regulates nociception by hydrolyzing AMP to adenosine in nociceptive circuits and
      represents a new molecular target for the treatment of chronic pain. Moreover,
      our data suggest NT5E is well localized to regulate nucleotide signaling between
      skin cells and sensory axons.

PMID- 20147552
TI  - The guanine exchange factor vav controls axon growth and guidance during
      Drosophila development.
AB  - The Vav proteins are guanine exchange factors (GEFs) that trigger the activation
      of the Rho GTPases in general and the Rac family in particular. While the role of
      the mammalian vav genes has been extensively studied in the hematopoietic system
      and the immune response, there is little information regarding the role of vav
      outside of these systems. Here, we report that the single Drosophila vav homolog
      is ubiquitously expressed during development, although it is enriched along the
      embryonic ventral midline and in the larval eye discs and brain. We have analyzed
      the role that vav plays during development by generating Drosophila null mutant
      alleles. Our results indicate that vav is required during embryogenesis to
      prevent longitudinal axons from crossing the midline. Later on, during larval
      development, vav is required within the axons to regulate photoreceptor axon
      targeting to the optic lobe. Finally, we demonstrate that adult vav mutant
      escapers, which exhibit coordination problems, display axon growth defects in the
      ellipsoid body, a brain area associated with locomotion control. In addition, we
      show that vav interacts with other GEFs known to act downstream of guidance
      receptors. Thus, we propose that vav acts in coordination with other GEFs to
      regulate axon growth and guidance during development by linking guidance signals
      to the cytoskeleton via the modulation of Rac activity.

PMID- 20147554
TI  - Postnatal development of a segmental switch enables corticospinal tract
      transmission to spinal forelimb motor circuits.
AB  - Development of skilled movements and the corticospinal tract (CST) begin
      prenatally and continue postnatally. Because the CST is required for skilled
      movements in maturity, it is accepted that motor skills cannot occur until the
      CST develops a mature organization. We recently showed that the CST plays an
      essential role in postnatal development of interneurons comprising the spinal
      circuits it engages. We proposed that CST signals are more effectively
      transmitted to ventral motor circuits after interneuron maturation, thereby
      enabling expression of CST motor functions, suggesting development of a segmental
      switch promoting transmission. We tested this by recording CST-evoked focal
      synaptic potentials, extracellularly, in the cervical enlargement of cats before
      and after interneuron maturation [postnatal week 5 (PW5) to PW7]. We compared
      monosynaptic CST amplitude input to segmental circuits with oligosynaptic ventral
      horn responses, as a measure of CST-evoked segmental response transmission from
      input to output. The M1 primary motor cortex was unilaterally inactivated between
      PW5 and PW7 to determine activity dependence. CST interneuron contacts were
      identified using confocal microscopy. CST terminals contact diverse interneuron
      classes. CST stimulation strongly activated ventral motor circuits at the ages
      when both interneurons and CST spinal terminations have developed a mature
      phenotype, supporting development of segmental transmission of CST signals. CST
      activity blockade impeded development of effective segmental transmission by the
      inactivated CST and created a novel path for transmission from the ipsilateral,
      unaffected, CST. Our findings show that development of segmental CST signal
      transmission regulates nascent CST motor control functions and provide insight
      into systems-level mechanisms for protracted motor skill development.

PMID- 20147553
TI  - A surface-based analysis of hemispheric asymmetries and folding of cerebral
      cortex in term-born human infants.
AB  - We have established a population average surface-based atlas of human cerebral
      cortex at term gestation and used it to compare infant and adult cortical shape
      characteristics. Accurate cortical surface reconstructions for each hemisphere of
      12 healthy term gestation infants were generated from structural magnetic
      resonance imaging data using a novel segmentation algorithm. Each surface was
      inflated, flattened, mapped to a standard spherical configuration, and registered
      to a target atlas sphere that reflected shape characteristics of all 24
      contributing hemispheres using landmark constrained surface registration.
      Population average maps of sulcal depth, depth variability, three-dimensional
      positional variability, and hemispheric depth asymmetry were generated and
      compared with previously established maps of adult cortex. We found that cortical
      structure in term infants is similar to the adult in many respects, including the
      pattern of individual variability and the presence of statistically significant
      structural asymmetries in lateral temporal cortex, including the planum temporale
      and superior temporal sulcus. These results indicate that several features of
      cortical shape are minimally influenced by the postnatal environment.

PMID- 20147555
TI  - Reduced laterality as a trait marker of schizophrenia--evidence from structural
      and functional neuroimaging.
AB  - Laterality is a characteristic principle of the organization of the brain systems
      for language, and reduced hemispheric asymmetry has been considered a risk factor
      for schizophrenia. Here we sought support for the risk factor hypothesis by
      investigating whether reduced asymmetry of temporal lobe structure and function
      is also present in unaffected relatives. Sixteen schizophrenia patients, 16 age
      matched first-degree relatives, and 15 healthy controls underwent high-resolution
      three-dimensional anatomical imaging and functional magnetic resonance imaging
      during auditory stimulation. Both the overall auditory cortex and planum
      temporale volumes and the lateralization to the left hemisphere were markedly
      reduced in patients. The decrease of lateralization correlated with increased
      severity of symptoms. In addition, both the overall functional activation in
      response to auditory stimulation and its asymmetry were reduced in the patients.
      Relatives had intermediate values between patients and controls on both
      structural and functional measures. This study provides added support for the
      idea that reduced hemispheric asymmetry is a biological risk factor for
      schizophrenia.

PMID- 20147557
TI  - Ca2+/calmodulin disrupts AKAP79/150 interactions with KCNQ (M-Type) K+ channels.
AB  - M-type channels are localized to neuronal, cardiovascular, and epithelial
      tissues, where they play critical roles in control of excitability and K(+)
      transport, and are regulated by numerous receptors via G(q/11)-mediated signals.
      One pathway shown for KCNQ2 and muscarinic receptors uses PKC, recruited to the
      channels by A-kinase anchoring protein (AKAP)79/150. As M-type channels can be
      variously composed of KCNQ1-5 subunits, and M current is known to be regulated by
      Ca(2+)/calmodulin (CaM) and PIP(2), we probed the generality of AKAP79/150
      actions among KCNQ1-5 channels, and the influence of Ca(2+)/CaM and PIP(2) on
      AKAP79/150 actions. We first examined which KCNQ subunits are targeted by AKAP79
      in Chinese hamster ovary (CHO) cells heterologously expressing KCNQ1-5 subunits
      and AKAP79, using fluorescence resonance energy transfer (FRET) under total
      internal reflection fluorescence (TIRF) microscopy, and patch-clamp analysis.
      Donor-dequenching FRET between CFP-tagged KCNQ1-5 and YFP-tagged AKAP79 revealed
      association of KCNQ2-5, but not KCNQ1, with AKAP79. In parallel with these
      results, CHO cells stably expressing M(1) receptors studied under perforated
      patch-clamp showed cotransfection of AKAP79 to "sensitize" KCNQ2/3 heteromers and
      KCNQ2-5, but not KCNQ1, homomers to muscarinic inhibition, manifested by shifts
      in the dose-response relations to lower concentrations. The effect on KCNQ4 was
      abolished by the T553A mutation of the putative PKC phosphorylation site. We then
      probed the role of CaM and PIP(2) in these AKAP79 actions. TIRF/FRET experiments
      revealed cotransfection of wild-type, but not dominant-negative (DN), CaM that
      cannot bind Ca(2+), to disrupt the interaction of YFP-tagged AKAP79(1-153) with
      CFP-tagged KCNQ2-5. Tonic depletion of PIP(2) by cotransfection of a PIP(2)
      phosphatase had no effect, and sudden depletion of PIP(2) did not delocalize GFP
      tagged AKAP79 from the membrane. Finally, patch-clamp experiments showed
      cotransfection of wild-type, but not DN, CaM to prevent the AKAP79-mediated
      sensitization of KCNQ2/3 heteromers to muscarinic inhibition. Thus, AKAP79 acts
      on KCNQ2-5, but not KCNQ1-containing channels, with effects disrupted by
      calcified CaM, but not by PIP(2) depletion.

PMID- 20147556
TI  - Hypocretins regulate the anxiogenic-like effects of nicotine and induce
      reinstatement of nicotine-seeking behavior.
AB  - Emerging evidence suggests that the hypocretinergic system is involved in
      addictive behavior. In this study, we investigated the role of these hypothalamic
      neuropeptides in anxiety-like responses of nicotine and stress-induced
      reinstatement of nicotine-seeking behavior. Acute nicotine (0.8 mg/kg, s.c.)
      induced anxiogenic-like effects in the elevated plus-maze and activated the
      paraventricular nucleus of the hypothalamus (PVN) as revealed by c-Fos
      expression. Pretreatment with the hypocretin receptor 1 (Hcrtr-1) antagonist
      SB334867 or preprohypocretin gene deletion blocked both nicotine effects. In the
      PVN, SB334867 also prevented the activation of corticotrophin releasing factor
      (CRF) and arginine-vasopressin (AVP) neurons, which expressed Hcrtr-1. In
      addition, an increase of the percentage of c-Fos-positive hypocretin cells in the
      perifornical and dorsomedial hypothalamic (PFA/DMH) areas was found after
      nicotine (0.8 mg/kg, s.c.) administration. Intracerebroventricular infusion of
      hypocretin-1 (Hcrt-1) (0.75 nmol/1 mul) or footshock stress reinstated a
      previously extinguished nicotine-seeking behavior. The effects of Hcrt-1 were
      blocked by SB334867, but not by the CRF1 receptor antagonist antalarmin.
      Moreover, SB334867 did not block CRF-dependent footshock-induced reinstatement of
      nicotine-seeking while antalarmin was effective in preventing this nicotine
      motivational response. Therefore, the Hcrt system interacts with CRF and AVP
      neurons in the PVN and modulates the anxiogenic-like effects of nicotine whereas
      Hcrt and CRF play a different role in the reinstatement of nicotine-seeking.
      Indeed, Hcrt-1 reinstates nicotine-seeking through a mechanism independent of CRF
      activation whereas CRF mediates the reinstatement induced by stress.

PMID- 20147558
TI  - A genetic model of chronic rhinosinusitis-associated olfactory inflammation
      reveals reversible functional impairment and dramatic neuroepithelial
      reorganization.
AB  - Inflammatory sinus and nasal disease is a common cause of human olfactory loss.
      To explore the mechanisms underlying rhinosinusitis-associated olfactory loss, we
      have generated a transgenic mouse model of olfactory inflammation, in which tumor
      necrosis factor alpha (TNF-alpha) expression is induced in a temporally
      controlled manner specifically within the olfactory epithelium (OE). Like the
      human disease, TNF-alpha expression leads to a progressive infiltration of
      inflammatory cells into the OE. Using this model, we have defined specific phases
      of the pathologic process. An initial loss of sensation without significant
      disruption is observed, followed by a striking reorganization of the sensory
      neuroepithelium. An inflamed and disrupted state is sustained chronically by
      continued induction of cytokine expression. After prolonged maintenance in a
      deficient state, there is a dramatic recovery of function and a normal histologic
      appearance when TNF-alpha expression is extinguished. Although obstruction of
      airflow is also a contributing factor in human rhinosinusitis, this in vivo model
      demonstrates for the first time that direct effects of inflammation on OE
      structure and function are important mechanisms of olfactory dysfunction. These
      features mimic essential aspects of chronic rhinosinusitis-associated olfactory
      loss, and illuminate underlying cellular and molecular aspects of the disease.
      This manipulable model also serves as a platform for developing novel therapeutic
      interventions.

PMID- 20147559
TI  - Mechanisms underlying lateral GABAergic feedback onto rod bipolar cells in rat
      retina.
AB  - GABAergic feedback inhibition from amacrine cells shapes visual signaling in the
      inner retina. Rod bipolar cells (RBCs), ON-sensitive cells that depolarize in
      response to light increments, receive reciprocal GABAergic feedback from A17
      amacrine cells and additional GABAergic inputs from other amacrine cells located
      laterally in the inner plexiform layer. The circuitry and synaptic mechanisms
      underlying lateral GABAergic inhibition of RBCs are poorly understood. A-type and
      rho-subunit-containing (C-type) GABA receptors (GABA(A)Rs and GABA(C)Rs) mediate
      both forms of inhibition, but their relative activation during synaptic
      transmission is unclear, and potential interactions between adjacent reciprocal
      and lateral synapses have not been explored. Here, we recorded from RBCs in acute
      slices of rat retina and isolated lateral GABAergic inhibition by
      pharmacologically ablating A17 amacrine cells. We found that amacrine cells
      providing lateral GABAergic inhibition to RBCs receive excitatory synaptic input
      mostly from ON bipolar cells via activation of both Ca(2+)-impermeable and Ca(2+)
      permeable AMPA receptors (CP-AMPARs) but not NMDA receptors (NMDARs). Voltage
      gated Ca(2+) (Ca(v)) channels mediate the majority of Ca(2+) influx that triggers
      GABA release, although CP-AMPARs contribute a small component. The intracellular
      Ca(2+) signal contributing to transmitter release is amplified by Ca(2+)-induced
      Ca(2+) release from intracellular stores via activation of ryanodine receptors.
      Furthermore, lateral nonreciprocal feedback is mediated primarily by GABA(C)Rs
      that are activated independently from receptors mediating reciprocal feedback
      inhibition. These results illustrate numerous physiological differences that
      distinguish GABA release at reciprocal and lateral synapses, indicating complex,
      pathway-specific modulation of RBC signaling.

PMID- 20147561
TI  - High-frequency stimulation of the subthalamic nucleus and L-3,4
      dihydroxyphenylalanine inhibit in vivo serotonin release in the prefrontal cortex
      and hippocampus in a rat model of Parkinson's disease.
AB  - High-frequency stimulation of the subthalamic nucleus (STN-HFS) and l-3,4
      dihydroxyphenylalanine (l-DOPA) medication are the most used therapeutic
      approaches in Parkinson's disease (PD), but their beneficial motor effects are
      burdened by the emergence of cognitive and depressive disorders. Although a
      reduced serotonergic function has been linked to the psychiatric effects of
      antiparkinsonian treatments, biochemical evidence supporting this hypothesis is
      still lacking. By using a microdialysis approach in anesthetized rats, we
      investigated the ability of STN-HFS (130 Hz, 30 muA, 20 min) and l-DOPA (6-12
      mg/kg) to change extracellular levels of serotonin (5-HT) monitored
      simultaneously in the prefrontal cortex (PFC) and hippocampus (HIPP), two brain
      regions involved in the regulation of mood and cognition that receive a distinct
      5-HT innervation. The results show that STN-HFS inhibited 5-HT levels in the PFC
      and HIPP of sham-lesioned and 6-hydroxydopamine (6-OHDA)-lesioned rats. The
      effect elicited by STN-HFS was blocked by the administration of the 5-HT(1A)
      agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin. l-DOPA (6 and 12 mg/kg) reduced 5
      HT levels in the PFC and HIPP of 6-OHDA rats. STN-HFS did not further decrease 5
      HT levels induced by l-DOPA, but attenuated l-DOPA-induced dopamine release in
      the PFC and HIPP. These neurochemical data show that STN-HFS inhibits 5-HT
      release by modulating serotonergic neuron activity, while the decrease in 5-HT
      levels induced by l-DOPA may include its direct action inside serotonergic
      neurons. These results support the premise that antiparkinsonian treatments
      reduce central serotonergic transmission, which may favor the development of
      nonmotor side effects in PD.

PMID- 20147560
TI  - A probabilistic strategy for understanding action selection.
AB  - Brain regions involved in transforming sensory signals into movement commands are
      the likely sites where decisions are formed. Once formed, a decision must be read
      out from the activity of populations of neurons to produce a choice of action.
      How this occurs remains unresolved. We recorded from four superior colliculus
      neurons simultaneously while monkeys performed a target selection task. We
      implemented three models to gain insight into the computational principles
      underlying population coding of action selection. We compared the population
      vector average (PVA)/optimal linear estimator (OLE) and winner-takes-all (WTA)
      models and a Bayesian model, maximum a posteriori estimate (MAP), to determine
      which predicted choices most often. The probabilistic model predicted more trials
      correctly than both the WTA and the PVA. The MAP model predicted 81.88%, whereas
      WTA predicted 71.11% and PVA/OLE predicted the least number of trials at 55.71
      and 69.47%. Recovering MAP estimates using simulated, nonuniform priors that
      correlated with monkeys' choice performance, improved the accuracy of the model
      by 2.88%. A dynamic analysis revealed that the MAP estimate evolved over time and
      the posterior probability of the saccade choice reached a maximum at the time of
      the saccade. MAP estimates also scaled with choice performance accuracy. Although
      there was overlap in the prediction abilities of all the models, we conclude that
      movement choice from populations of neurons may be best understood by considering
      frameworks based on probability.

PMID- 20147562
TI  - The P2Y2 receptor sensitizes mouse bladder sensory neurons and facilitates
      purinergic currents.
AB  - Sensitization of bladder afferents is an underlying contributor to the
      development and maintenance of painful bladder syndrome/interstitial cystitis.
      Extracellular purines and pyrimidines (e.g., ATP and UTP), released during
      bladder distension or from damaged cells after tissue insult, are thought to play
      an important role in bladder physiological and pathological states by actions at
      ionotropic P2X and metabotropic P2Y receptors. In the present study, we examined
      the ability of P2Y receptors to sensitize and modulate P2X-mediated responses in
      mouse bladder sensory neurons. UTP (a P2Y(2) and P2Y(4) agonist) increased
      excitability of bladder neurons by depolarizing resting membrane potential,
      increasing action potential firing, and facilitating responses to suprathreshold
      current injection as well as to P2X agonist application. These effects of UTP on
      bladder neuron excitability were blocked by the P2Y(2) receptor antagonist
      suramin. UTP also facilitated bladder neuron homomeric P2X(2) sustained currents
      and homomeric P2X(3) fast currents. The facilitatory effect of UTP on P2X(2)
      sustained currents was mediated by a G-protein-coupled P2Y(2) receptor/PKC
      pathway, whereas the effect of UTP on P2X(3) fast currents was G-protein
      independent. We also examined P2X and P2Y receptor expression in bladder neurons.
      P2Y(2) and P2Y(4) transcripts were detected in approximately 50 and approximately
      20% of bladder neurons, respectively. Approximately 50% of P2X(2)- and P2X(3)
      positive bladder neurons expressed P2Y(2) transcripts, whereas < or =25% of the
      same bladder neurons expressed P2Y(4) transcripts. These results support
      involvement of P2Y(2) receptors in bladder sensation, suggesting an important
      contribution to bladder neuron excitability and hypersensitivity.

PMID- 20147564
TI  - Multisegmental A{delta}- and C-fiber input to neurons in lamina I and the lateral
      spinal nucleus.
AB  - Spinal lamina I and the lateral spinal nucleus (LSN) receive and integrate
      nociceptive primary afferent inputs to project through diverse ascending
      pathways. The pattern of the afferent supply of individual lamina I and LSN
      neurons through different segmental dorsal roots is poorly understood. Therefore,
      we recorded responses of lamina I and LSN neurons in spinal segments L4 and L3 to
      stimulation of six ipsilateral dorsal roots (L1-L6). The neurons were viewed
      through the overlying white matter in the isolated spinal cord preparation using
      the oblique infrared LED illumination technique. Orientation of myelinated fibers
      in the white matter was used as a criterion to distinguish between the LSN and
      lamina I. Both types of neurons received mixed (monosynaptic and polysynaptic)
      excitatory Adelta- and C-fiber input from up to six dorsal roots, with only less
      than one-third of it arising from the corresponding segmental root. The largest
      mixed input arose from the dorsal root of the neighboring caudal segment. Lamina
      I and LSN neurons could fire spikes upon the stimulation of up to six different
      dorsal roots. We also found that individual lamina I neurons can receive
      converging monosynaptic Adelta- and/or C-fiber inputs from up to six segmental
      roots. This study shows that lamina I and LSN neurons function as intersegmental
      integrators of primary afferent inputs. We suggest that broad monosynaptic
      convergence of Adelta- and C-afferents onto a lamina I neuron is important for
      the somatosensory processing.

PMID- 20147563
TI  - Keeping it together: mechanisms of intersegmental coordination for a flexible
      locomotor behavior.
AB  - The coordination of multiple neural oscillators is key for the generation of
      productive locomotor movements. In the medicinal leech, we determined that
      activation and coordination of the segmental crawl oscillators, or unit burst
      generators, are dependent on signals descending from the cephalic ganglion. In
      nearly intact animals, removing descending input (reversibly with a sucrose
      block) prevented overt crawling, but not swimming. Cephalic depolarization was
      sufficient for coordination. To determine whether descending signals were
      necessary for the generation and maintenance of posterior-directed intersegmental
      phase delays, we induced fictive crawling in isolated whole nerve cords using
      dopamine (DA) and blocked descending inputs. After blockade, we observed a
      significant loss of intersegmental coordination. Appropriate phase delays were
      also absent in DA-treated chains of ganglia. In chains, when one ganglion was
      removed from its neighbors, crawling in that ganglion emerged robust and stable,
      underscoring that these oscillators operate best with either all or none of their
      intersegmental inputs. To study local oscillator coupling, we induced fictive
      crawling (with DA) in a single oscillator within a chain. Although appropriate
      intersegmental phase delays were always absent, when one ganglion was treated
      with DA, neighboring ganglia began to show crawl-like bursting, with motoneuron
      spikes/burst greatest in untreated posterior ganglia. We further determined that
      this local excitatory drive excluded the swim-gating cell, 204. In conclusion,
      both long-distance descending and local interoscillator coupling contribute to
      crawling. This dual contribution helps to explain the inherent flexibility of
      crawling, and provides a foundation for understanding other dynamic locomotor
      behaviors across animal groups.

PMID- 20147566
TI  - Students with brain tumors: their post-treatment perceptions of teachers, peers,
      and academics and retrospective views on school during treatment.
AB  - The purpose of this pilot study was: (1) to determine how students surviving
      brain tumors (BTs) perceive their teachers' responses to them, their own academic
      performance, and their interactions with peers at school using a new measure; and
      (2) to describe students' retrospective perceptions of schooling while undergoing
      treatment. Using a sample of 22 students treated for a BT (ages 9-18) and 22
      comparison (ages 8-19), no significant BT-control group differences regarding
      perceptions of teacher response, academic performance, and interactions with
      peers at school were found. Generally, students with BTs reported positive school
      experiences during treatment including favorable perceptions of their teachers'
      effectiveness, enjoyment of schoolwork, and the quality of their schooling.
      Additionally, they felt that completing schoolwork during treatment was
      important. The results of this study may provide insight into the perceived
      psychosocial adjustment and academic performance of students with BTs during and
      after treatment.

PMID- 20147565
TI  - A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a
      critical role in modulating dopamine-dependent behaviors.
AB  - Acetylcholine (ACh) regulates many key functions of the CNS by activating cell
      surface receptors referred to as muscarinic ACh receptors (M(1)-M(5) mAChRs).
      Like other mAChR subtypes, the M(4) mAChR is widely expressed in different
      regions of the forebrain. Interestingly, M(4) mAChRs are coexpressed with D(1)
      dopamine receptors in a specific subset of striatal projection neurons. To
      investigate the physiological relevance of this M(4) mAChR subpopulation in
      modulating dopamine-dependent behaviors, we used Cre/loxP technology to generate
      mutant mice that lack M(4) mAChRs only in D(1) dopamine receptor-expressing
      cells. The newly generated mutant mice displayed several striking behavioral
      phenotypes, including enhanced hyperlocomotor activity and increased behavioral
      sensitization following treatment with psychostimulants. These behavioral changes
      were accompanied by a lack of muscarinic inhibition of D(1) dopamine receptor
      mediated cAMP stimulation in the striatum and an increase in dopamine efflux in
      the nucleus accumbens. These novel findings demonstrate that a distinct
      subpopulation of neuronal M(4) mAChRs plays a critical role in modulating several
      important dopamine-dependent behaviors. Since enhanced central dopaminergic
      neurotransmission is a hallmark of several severe disorders of the CNS, including
      schizophrenia and drug addiction, our findings have substantial clinical
      relevance.

PMID- 20147567
TI  - 'I've just taken you to see the man with the CD on his head': the experience and
      management of recurrent sore throat in children.
AB  - Tonsillectomies for children with recurrent sore throat are common. There is a
      perception amongst medical professionals that parents are eager for surgical
      intervention but the parent/child perspective is overlooked in the literature.
      This study aimed to identify parent/child experience of recurrent sore throat.
      The study was qualitative, using grounded theory approach to data
      collection/analysis. Semi-structured, in-depth, interviews were conducted with 12
      dyads of children (aged 4-16) and their parents, attending two Ear, Nose and
      Throat outpatient clinics held at a hospital in North East England, referred by
      their General Practitioner for recurrent sore throats. Analysis revealed
      recurrent sore throats significantly affected the families' quality of life.
      Families felt the need for antibiotics and tonsillectomies although parent and
      child were not always in agreement over their choice of treatment. Families felt
      empowered when the health care system showed some flexibility, such as allowing
      self re-referral, giving families greater choice in the way they managed the
      condition. Policy makers need to be aware of the consequences of recurrent sore
      throats in children and the needs of families in managing this chronic condition.
      More flexible approaches to health care, such as self re-referral and use of
      waiting list to review symptoms, may be needed if the number of tonsillectomies
      is to be reduced.

PMID- 20147568
TI  - Aqueous extract of Trigonella foenum graecum (fenugreek) prevents cypermethrin
      induced hepatotoxicity and nephrotoxicity.
AB  - Cypermethrin (CM) is an important type II pyrethroid pesticide used extensively
      in pest control and is reported to cause hepatic and renal toxicity. Oxidative
      stress and lipid peroxidation (LPO) has been implicated in the toxicology of
      pyrethroids. Fenugreek is known for its antitoxic and antioxidant potential. We
      have investigated the protective effect of aqueous extract of germinated
      fenugreek seeds in CM-induced hepatic and renal toxicity. Male Wistar rats were
      treated with 1/10 LD(50) (25 mg/kg body weight) of CM and 10% aqueous extract of
      fenugreek (GFaq) for 60 days. CM treatment caused increased thiobarbituric acid
      reactive substances (TBARS), depletion in glutathione (GSH) and reduction in the
      activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
      (GPx) and glutathione-S-transferase (GST) in liver and kidneys. There was a
      significant reduction in total phospholipids and increased activities of
      phospholipases A (PLA) and C (PLC) in liver and kidneys and increased activities
      of serum marker enzymes, aspartate transaminase (AST), alanine tansaminase (ALT),
      alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl
      transferase (GGT). Treatment with 10% GFaq showed replenishment of antioxidant
      status and brought all the values to near normal, indicating the protective
      effect of fenugreek. Phytochemicals present in fenugreek could play an important
      role in ameliorating the pesticide-induced toxicity.

PMID- 20147569
TI  - Reactivity to smoking- and food-related cues in currently dieting and non-dieting
      young women smokers.
AB  - There is some evidence to suggest that young women dieters who smoke experience
      greater cigarette cravings in the presence of food-related related cues. The aim
      of this experiment was to examine reactivity to both smoking-related and water
      cues by dieting and non-dieting women smokers in the presence or absence of food
      cues. Eighteen female undergraduates attended two sessions (food present and food
      absent). At each session, participants were presented with a cigarette and water
      cue in a counterbalanced order. Pre- and post-cue measures included the brief
      version of the Questionnaire for Smoking Urges, heart rate and self-reported
      mood. All smokers showed enhanced reactivity (increased craving and heart rate)
      to smoking versus water cues. For dieters there was a larger increase in
      cigarette craving and heart rate in response to the smoking-related cues in the
      presence of food compared with the absence of food, whereas for non-dieters there
      was a smaller increase in cigarette craving and heart rate in response to the
      smoking-related cues in the presence of food compared with the absence of food.
      Mood and appetite ratings were not significantly affected by either cue type or
      session. The results suggest that cue reactivity to smoking-related cues is
      modulated by the presence of incentive stimuli relevant to the individual.

PMID- 20147570
TI  - A pharmacological tool to assess vasopressinergic co-activation of the
      hypothalamus-pituitary-adrenal axis more integrally in healthy volunteers.
AB  - Pharmacological function tests consisting of 100 ug hCRH (corticorelin) and 10 ug
      dDAVP (desmopressin) mimic endogenous hypothalamus-pituitary-adrenal (HPA) axis
      activation. However, physiological CRH concentrations preclude informative
      vasopressinergic co-activation (using dDAVP) and independent quantification of
      both corticotrophinergic (using hCRH) and vasopressinergic (using dDAVP)
      activation is limited due to administration on separate occasions. This
      randomized, double-blind, placebo-controlled, partial five-way crossover study in
      healthy males and females (six : six) examined whether (1) concomitant
      administration of dDAVP and hCRH provides more informative vasopressinergic co
      activation than dDAVP alone; and (2) whether the administration of dDAVP followed
      two hours later by hCRH can quantify both vasopressinergic and
      corticotrophinergic activation on a single test day. Combining 10 ug dDAVP with
      10 ug and 30 ug hCRH caused dose-related ACTH and cortisol release which was
      larger than with 10 ug dDAVP alone and respectively comparable to and greater
      than that induced by 100 ug hCRH. Using 10 ug dDAVP alone demonstrated limited
      ACTH release while the effects of 100 ug hCRH two hours later were three times as
      large. ACTH and cortisol released by 10 ug dDAVP returned to baseline prior to
      100 ug hCRH administration and dDAVP did not influence the response to subsequent
      hCRH administration. Dose-related vasopressinergic co-activation of the HPA axis
      was induced by combining 10 ug dDAVP with 10 ug and 30 ug hCRH. Combining 10 ug
      dDAVP with 10 ug hCRH induced the potentially most informative vasopressinergic
      co-activation since it is not restricted by ceiling or flooring effects. The hCRH
      response was not affected by prior dDAVP, allowing for a practical function test
      examining both HPA activation routes on the same day.

PMID- 20147571
TI  - MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non
      sedating anxiolytic in preclinical species but causes sedation in humans.
AB  - MRK-409 binds to alpha1-, alpha2-, alpha3- and alpha5-containing human
      recombinant GABA(A) receptors with comparable high affinity (0.21-0.40 nM).
      However, MRK-409 has greater agonist efficacy at the alpha3 compared with alpha1
      subtypes (respective efficacies relative to the full agonist chlordiazepoxide of
      0.45 and 0.18). This compound readily penetrates the brain in rats and occupies
      the benzodiazepine site of GABA(A) receptors, measured using an in vivo
      [(3)H]flumazenil binding assay, with an Occ(50) of 2.2 mg/kg p.o. and a
      corresponding plasma EC(50) of 115 ng/mL. Behaviourally, the alpha3-preferring
      agonist efficacy profile of MRK-409 produced anxiolytic-like activity in rodent
      and primate unconditioned and conditioned models of anxiety with minimum
      effective doses corresponding to occupancies, depending on the particular model,
      ranging from ~35% to 65% yet there were minimal overt signs of sedation at
      occupancies greater than 90%. In humans, however, safety and tolerability studies
      showed that there was pronounced sedation at a dose of 2 mg, resulting in a
      maximal tolerated dose of 1 mg. This 2 mg dose corresponded to a C(max) plasma
      concentration of 28 ng/mL, which, based on the rodent plasma EC(50) for occupancy
      of 115 ng/mL, suggested that sedation in humans occurs at low levels of
      occupancy. This was confirmed in human positron emission tomography studies, in
      which [(11)C]flumazenil uptake following a single dose of 1 mg MRK-409 was
      comparable to that of placebo, indicating that occupancy of GABA(A) receptor
      benzodiazepine binding sites by MRK-409 was below the limits of detection (i.e.
      <10%). Taken together, these data show that MRK-409 causes sedation in humans at
      a dose (2 mg) corresponding to levels of occupancy considerably less than those
      predicted from rodent models to be required for anxiolytic efficacy (~35-65%).
      Thus, the preclinical non-sedating anxiolytic profile of MRK-409 did not
      translate into humans and further development of this compound was halted.

PMID- 20147573
TI  - A naturalistic controlled study of relapsing schizophrenic patients with tardive
      dyskinesia and supersensitivity psychosis.
AB  - Despite advances in treatments, relapses in schizophrenia still occur. The causes
      of relapse are not always apparent, especially for patients that are compliant
      with medication. One possibility is that the brain adapts to long-term
      antipsychotic drug treatment, leading to tolerance and withdrawal symptoms. This
      has been described as supersensitivity psychosis. Tardive dyskinesia is also
      thought to occur as a consequence of dopamine supersensitivity caused by chronic
      treatment with antipsychotics. Another associated feature is sensitivity to life
      stress. This study investigated the relationship between abnormal movements, life
      events and drug treatment in patients relapsing on antipsychotics with high
      potency at the dopamine D2 receptor. Twenty-two patients from a cohort of 128
      patients experiencing a psychotic relapse were assessed; of these, seven (32%)
      met criteria for the presence of abnormal involuntary movements. These subjects
      were found to be clinically distinct from the subjects without abnormal
      movements. They tended to be older with a greater duration of illness and higher
      dosage of antipsychotics but more symptoms of psychosis compared with the other
      subjects. Relapse was also associated with minor life events. The association
      between abnormal involuntary movements and high levels of psychotic symptoms
      suggests that dopamine sensitization/supersensitivity may underlie both
      phenomena. These results suggest that clinicians may have to consider alternative
      dosing strategies, novel agents or switching to one of the antipsychotics that
      have a lower affinity for the D2 receptor.

PMID- 20147572
TI  - Evaluation of the subjective and reinforcing effects of diphenhydramine,
      levetiracetam, and valproic acid.
AB  - Few unscheduled sedating medications have been evaluated for their subjective and
      reinforcing effects in humans. To increase the information available about
      unscheduled sedating medications and to evaluate the ability of human laboratory
      measures to discriminate between scheduled and unscheduled sedating drugs, 24
      subjects with a history of experience with several classes of drugs of abuse,
      including sedatives and/or alcohol, and who reported liking a test dose of
      pentobarbital 300 mg, were randomized to single doses of diphenhydramine 400 mg,
      levetiracetam 4000 mg, valproic acid 1500 mg, diazepam 30 mg or placebo in a
      double-blind, 5-way crossover study. On the Addiction Research Center Inventory
      Morphine-Benzedrine Group and the Next Day Questionnaire measures 'Take Again'
      and 'Willing to Pay', diazepam produced a significantly greater effect than
      placebo; all three other active drugs did not. Levetiracetam significantly
      increased the crossover point on the Multiple Choice Procedure, whereas diazepam
      did not. For the doses studied, the rank order of statistically significant
      findings suggestive of abuse potential was diazepam (9/10 measures significant) >
      levetiracetam (6/10) > diphenhydramine (5/10) > valproic acid (2/10).

PMID- 20147574
TI  - Pattern of acute induction of Homer1a gene is preserved after chronic treatment
      with first- and second-generation antipsychotics: effect of short-term drug
      discontinuation and comparison with Homer1a-interacting genes.
AB  - Homer1a is a glutamate-related gene whose expression is induced by antipsychotics
      acutely (i.e. 90 min after treatment). Acute Homer1a expression is preserved
      after prolonged antipsychotic treatments, while the effects of short-term
      discontinuation after chronic antipsychotic treatment have not yet been assessed.
      Here, we studied early and long-term effects on gene expression by antipsychotics
      for Homer1a and other components of glutamatergic synapses. In the first
      paradigm, we evaluated Homer1a acute expression by single administration of
      antipsychotics (haloperidol 0.8 mg/kg, ziprasidone 10 and 4 mg/kg, clozapine 15
      mg/kg). Haloperidol and ziprasidone induced Homer1a in the striatum. Induction by
      ziprasidone was dose-dependent. These results suggest that acute Homer1a
      expression correlates with dopaminergic affinity and motor side effects of
      antipsychotics. In the second paradigm, we studied antipsychotic-mediated long
      term changes in Homer1a and glutamate-related genes. Rats were treated (21 days)
      with haloperidol 0.8 mg/kg, ziprasidone 4 mg/kg, or vehicle, and then sacrificed
      at 90 min (early time-point) or 24 h (delayed time-point) after last injection.
      Gene expression at these two time-points was compared. Homer1a preserved its
      pattern of expression at the early but not at the delayed time-point. Significant
      changes were also observed for PSD-95. The results suggest that Homer1a preserves
      its expression profile after chronic antipsychotics.

PMID- 20147576
TI  - Incidence and predictors of cetuximab hypersensitivity reactions in a North
      Carolina academic medical center.
AB  - OBJECTIVES: Previous research has indicated a high incidence of cetuximab
      hypersensitivity reactions in the southern US. This study documents the incidence
      of hypersensitivity reactions in North Carolina, and explores whether factors
      such as patient demographics, allergy history, premedications, and cancer type
      are potential predictors for cetuximab reactions. METHODS: This retrospective
      chart review consisted of 72 consecutively treated patients from Duke
      University's Morris Oncology treatment center between September 2005 and August
      2007. Data regarding stage of malignancy, premedications, and hypersensitivity
      reactions were collected from electronic databases. The number and type of
      reactions were characterized. Patients with and without hypersensitivity
      reactions were compared using bivariate statistics and multivariate logistic
      regression. RESULTS: Of the 72 patients, 21 (29%) experienced hypersensitivity
      reactions. The majority of reactions (62%) were grades III or IV. Of the 21
      patients having a reaction, 9 (43%) were sent to the emergency room and 5 (24%)
      had an overnight hospitalization. Three hospitalized patients were admitted to
      the intensive care unit. Both male gender (p = 0.039) and head/neck cancer (p =
      0.014) were related to an increased likelihood of hypersensitivity reaction in
      bivariate analyses. In multivariate analyses, controlling for demographics,
      allergy history, premedications, and cancer type/stage, only type of cancer was
      predictive of hypersensitivity reaction (colon vs head/neck OR = 0.177; 95% CI
      0.036-0.858). CONCLUSION: This study confirms a high rate of cetuximab
      hypersensitivity reactions in a southern region of the US. Patients with
      head/neck cancers were significantly more likely to have hypersensitivity
      reactions than patients with colon cancers.

PMID- 20147575
TI  - Escitalopram--translating molecular properties into clinical benefit: reviewing
      the evidence in major depression.
AB  - The majority of currently marketed drugs contain a mixture of enantiomers;
      however, recent evidence suggests that individual enantiomers can have
      pharmacological properties that differ importantly from enantiomer mixtures.
      Escitalopram, the S-enantiomer of citalopram, displays markedly different
      pharmacological activity to the R-enantiomer. This review aims to evaluate
      whether these differences confer any significant clinical advantage for
      escitalopram over either citalopram or other frequently used antidepressants.
      Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts
      of the retrieved studies were reviewed independently by both authors for
      inclusion. Only those studies relating to depression or major depressive disorder
      were included. The search identified over 250 citations, of which 21 studies and
      18 pooled or meta-analyses studies were deemed suitable for inclusion. These
      studies reveal that escitalopram has some efficacy advantage over citalopram and
      paroxetine, but no consistent advantage over other selective serotonin reuptake
      inhibitors. Escitalopram has at least comparable efficacy to available serotonin
      norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer
      some tolerability advantages over these agents. This review suggests that the
      mechanistic advantages of escitalopram over citalopram translate into clinical
      efficacy advantages. Escitalopram may have a favourable benefit-risk ratio
      compared with citalopram and possibly with several other antidepressant agents.

PMID- 20147577
TI  - The influence of fathers' socioeconomic status and paternity leave on
      breastfeeding duration: a population-based cohort study.
AB  - AIM: The propensity to breastfeed is a matter of public concern because of the
      favourable effects for infants. However, very few studies have described the
      influence of paternal variables upon duration of breastfeeding. The aim of this
      study was to describe the effects of fathers' socioeconomic status and their use
      of paternity leave on breastfeeding duration for infants up to 1 year of age.
      METHODS: A prospective population-based cohort study was undertaken. Data on
      breastfeeding, registered in databases in two Swedish counties for 1993-2001,
      were matched with data on socioeconomic status and paternity leave obtained from
      Statistics Sweden. Fathers of 51,671 infants were identified and included.
      RESULTS: Infants whose fathers had a lower level of education, were receiving
      unemployment benefit and/or had a lower equivalent disposable household income
      were significantly less likely to be breastfed at 2, 4, 6, 9, and 12 months of
      age. Infants whose fathers did not take paternity leave during the infant's first
      year were significantly less likely to be breastfed at 2 (p < 0.001), 4 (p <
      0.001), and 6 months (p < 0.001). CONCLUSIONS: This paper shows that an enabling
      of an increased involvement from fathers during the infants' first year of life,
      such as by paid paternity leave, may have beneficial effects on breastfeeding up
      to 6 months of age. A more systematic approach to supporting fathers' involvement
      may be particularly valuable to those infants whose fathers have a lower
      socioeconomic status.

PMID- 20147578
TI  - Biological pretreatment enhances biogas production in the anaerobic digestion of
      pulp and paper sludge.
AB  - High efficient resource recovery from pulp and paper sludge (PPS) has been the
      focus of attention. The objective of this research was to develop a bio
      pretreatment process prior to anaerobic digestion of PPS to improve the methane
      productivity. Active and inactive mushroom compost extracts (MCE) were used for
      pretreating PPS, followed by anaerobic digestion with monosodium glutamate waste
      liquor (MGWL). Laboratory-scale experiments were carried out in completely mixed
      bioreactors, 1-L capacity with 700 ml useful capacity. Optimal amount of active
      MCE for organics' solubilization in the step of pretreatment was 250 A.U./gVS(
      sludge). Under this condition, the PPS floc structure was well disrupted,
      resulting in void rate and fibre size diminishment after pretreatment. In
      addition, SCOD and VS removal were found to be 56% and 43.6%, respectively, after
      anaerobic digestion, being the peak value of VFA concentration determined as 1198
      mg acetic acid L(-1). The anaerobic digestion efficiency of PPS with and without
      pretreatment was evaluated. The highest methane yield under optimal pretreatment
      conditions was 0.23 m(3) CH4/kgVS(add), being 134.2% of the control. The results
      indicated that MCE bio-pretreatment could be a cost-effective and environmentally
      sound method for producing methane from PPS.

PMID- 20147579
TI  - Ankle--brachial index predicts level of, but not change in, cognitive function:
      the Edinburgh Artery Study at the 15-year follow-up.
AB  - The ankle-brachial index (ABI), a marker of generalized atherosclerosis, is
      related to cognitive impairment in older adults. We investigated whether ABI is
      associated specifically with age-related cognitive decline. We measured ABI at
      recruitment and 5 and 12 years later in a sample of individuals aged 55-74 years.
      Cognition was measured in 717 of these participants 10 years after recruitment
      and 5 years later. It was found that ABI was associated with the level of
      cognitive function, even after adjustment for estimated premorbid function and
      concurrently measured anxiety and depression (standardized coefficient of 0.07),
      but this was attenuated by anxiety and depression. ABI was not associated with
      change in cognitive function. In conclusion, over long time periods, low ABI may
      be associated with reduced cognitive function in older adults, at least partly
      because the associated poor health creates anxiety and depression.

PMID- 20147580
TI  - Sympathetic function in human carriers of melanocortin-4 receptor gene mutations.
AB  - CONTEXT: Melanocortinergic pathways clearly appear to be involved in obesity
      associated sympathetic overactivity and its hemodynamic and thermoregulatory
      consequences. Individuals with dysfunctional mutations in the melanocortin-4
      receptor gene (MC4R) are subject to obesity without developing hypertension.
      OBJECTIVE: This study aimed at characterizing the impact of the MC4R on
      sympathetic nerve traffic relevant to the cardiovascular system in humans.
      PARTICIPANTS: Participants included eight heterozygous carriers of MC4R mutations
      leading to a reduced function and control subjects matched for gender, age, and
      body mass index. MEASUREMENTS: We investigated vasoconstrictive muscle
      sympathetic nerve activity (MSNA), a direct measure of central sympathetic
      nervous outflow. MSNA was recorded microneurographically from the peroneal nerve
      at supine rest and during apnea-induced sympathoexcitation. Sympathetic activity
      was correlated with serum leptin levels and hemodynamic and anthropometric data.
      RESULTS: Individuals with MC4R impairment due to functional MC4R mutations were
      characterized by an inverse correlation between MSNA with body mass index and
      leptin levels, with the most obese subjects having the lowest MSNA. Resting MSNA,
      diastolic blood pressure, and heart rate tended to be lower in MC4R mutation
      carriers, and stimulated MSNA during apnea was significantly lower as compared
      with control subjects. CONCLUSION: The fact that obese subjects with MC4R
      mutations show an inverse relationship between obesity and MSNA suggests that
      central sympathetic outflow to the vasculature might depend on functional
      melanocortinergic pathways. Their dysfunction could explain reduced
      sympathoexcitability, lower sympathetic nerve-induced lipolysis, and the fact
      that blood pressure is rarely elevated in this type of obesity.

PMID- 20147581
TI  - Disparate outcomes from applying U.K. and U.S. osteoporosis treatment guidelines.
AB  - CONTEXT: After the advent of absolute fracture risk calculators, guidelines for
      the management of osteoporosis released by the U.S.-based National Osteoporosis
      Foundation (NOF) and the U.K.-based National Osteoporosis Guidelines Group (NOGG)
      differ markedly in their approaches to treatment recommendations. OBJECTIVE: The
      aim of the study was to apply the NOF and NOGG guidelines to a cohort of older
      women and compare the treatment recommendations with fracture outcomes over 5 yr
      for each algorithm. DESIGN AND SETTING: We conducted a cohort study of women who
      participated in a 5-yr randomized controlled trial of calcium supplementation at
      a clinical research center. PARTICIPANTS: We studied 1471 healthy, community
      dwelling, older women with mean age of 74 yr and mean follow-up of 4.4 yr. MAIN
      OUTCOME MEASURE: A total of 143 subjects (10%) sustained a nontraumatic
      osteoporotic fracture, and 21 sustained a nontraumatic hip fracture (1.4%).
      RESULTS: Applying the NOF guidelines required that 97% of participants undergo
      bone densitometry and 48% receive treatment. Seventy-six percent of hip fracture
      cases and 63% of osteoporotic fracture cases were identified for treatment.
      Applying the NOGG guidelines required that 13% of participants undergo bone
      densitometry and 21% receive treatment. Thirty-eight percent of hip fracture
      cases and 27% of osteoporotic fracture cases were identified for treatment.
      CONCLUSION: Treatment recommendations and fracture outcomes in older,
      predominantly osteopenic women differ substantially according to the management
      guideline applied. The NOGG guidelines identify only a minority of fracture
      cases; the NOF guidelines identify the majority of fracture cases, but at the
      expense of greater resource utilization. Both strategies lead to recommendations
      for reassurance in significant numbers of women who subsequently sustain
      fragility fractures.

PMID- 20147583
TI  - An inflammatory gene-expression fingerprint in monocytes of autoimmune thyroid
      disease patients.
AB  - CONTEXT: In monocytes of patients with autoimmune diabetes, we recently
      identified a gene expression fingerprint of two partly overlapping gene clusters,
      a PDE4B-associated cluster (consisting of 12 core proinflammatory
      cytokine/compound genes), a FABP5-associated cluster (three core genes), and a
      set of nine overlapping chemotaxis, adhesion, and cell assembly genes correlating
      to both PDE4B and FABP5. OBJECTIVE: Our objective was to study whether a similar
      monocyte inflammatory fingerprint as found in autoimmune diabetes is present in
      autoimmune thyroid disease (AITD). DESIGN AND PATIENTS: Quantitative PCR was used
      for analysis of 28 genes in monocytes of 67 AITD patients and 70 healthy
      controls. The tested 28 genes were the 24 genes previously found abnormally
      expressed in monocytes of autoimmune diabetes patients plus four extra genes
      found in whole-genome analysis of monocytes of AITD patients reported here.
      RESULTS: Monocytes of 24% of AITD and 50% of latent autoimmune diabetes of adults
      (LADA) patients shared an inflammatory fingerprint consisting of the set of 24
      genes of the PDE4B, FABP5, and overlapping gene sets. This study in addition
      revealed that FCAR, the gene for the Fcalpha receptor I, and PPBP, the gene for
      CXCL7, were part of this proinflammatory monocyte fingerprint. CONCLUSIONS: Our
      study provides an important tool to determine a shared, specific proinflammatory
      state of monocytes in AITD and LADA patients, enabling further research into the
      role of such proinflammatory cells in the failure to preserve tolerance in these
      conditions and of key fingerprint genes involved.

PMID- 20147582
TI  - Plasma adipokines, bone mass, and hip geometry in rural Chinese adolescents.
AB  - CONTEXT: Adipokines have been linked to bone phenotypes recently, but with
      conflicting results. Few such studies have been conducted in adolescents.
      OBJECTIVE: The aim of the study was to examine the associations of adiponectin
      and leptin with multiple bone phenotypes in Chinese adolescents and estimate the
      genetic contribution to these associations. DESIGN AND SETTING: This was a cross
      sectional study conducted in rural China. PARTICIPANTS: A total of 675 males and
      575 females aged 13-21 yr were included. OUTCOME MEASURES: Fat mass (FM), lean
      mass (LM), bone area (BA), bone mineral content (BMC), cross-sectional area
      (CSA), and section modulus (SM) were measured by dual-energy x-ray
      absorptiometry. Plasma adipokine concentration was determined using sandwich
      immunoassays. RESULTS: Adiponectin was inversely associated with all BMCs in
      males (P < 0.01), but not in females, after adjusting for LM, body weight, or BMI
      singly, or for LM and FM simultaneously. No such relationships were observed for
      CSA or SM in both genders. Leptin was inversely associated with all BAs, total
      hip BMC, CSA, and SM in both genders, when adjusting for body weight or BMI.
      These associations, except for whole-body BA and lumbar spine BA in females,
      disappeared when simultaneously adjusting for LM and FM. By Cholesky
      decomposition models using twin design, significant genetic correlations were
      detected between adiponectin and total-hip BMC in males and between leptin and
      total-hip BMC in both genders. CONCLUSIONS: We demonstrated that adiponectin and
      leptin were inversely associated with adolescent bone phenotypes but showed
      differential associations by gender, type of bone phenotypes, and adjustment of
      FM. This study also suggested that adipokines and bone phenotypes may share a
      common set of genes.

PMID- 20147584
TI  - Spontaneous hepatocellular carcinoma in captive prosimians.
AB  - Spontaneous hepatocellular carcinoma has been reported as a relatively common
      neoplasm in prosimians; however, the cause is unknown. To investigate possible
      pathogenic mechanisms, the authors performed a review of all adult animals from a
      captive prosimian population that had postmortem examinations over the past 10
      years. They performed a detailed histologic evaluation of all suspected
      proliferative liver lesions and diagnosed hepatocellular carcinoma in 14 of 145
      lemurs (9.7%). Affected animals ranged between the ages of 6 and 40 years old.
      The tumors had an unusually aggressive growth pattern for animal species;
      metastasis to the lungs or mediastinum was evident in 7 of 14 animals. Thirty-one
      animals-9 with hepatocellular carcinomas and 22 age-matched controls without
      hepatic neoplasia-were tested to evaluate the relationship between hepatic iron
      stores (as well as other trace metals) and the presence of hepatocellular
      carcinoma. There was no difference between the hepatic iron, copper, or
      molybdenum in lemurs with hepatocellular carcinoma and those without, suggesting
      that iron is not a key element in the pathogenesis of liver tumor formation.
      Analysis of 22 serum samples from animals with and without liver tumors indicated
      no evidence of active infection with a hepadnavirus, the virus family that
      includes hepatitis B virus. Hepatitis C virus and aflatoxin B1 were considered as
      potential causes and ruled out owing to lack of associated histopathologic
      lesions. In conclusion, hepatocellular neoplasia is relatively common in captive
      prosimians, although previously suspected etiologies seem unlikely.

PMID- 20147585
TI  - Eosinophilic airway inflammation in a cynomolgus monkey.
AB  - The present article describes an occurrence of eosinophilic airway inflammation
      of a 4-year-old female cynomolgus monkey in a vehicle control group of a routine
      toxicology study. Histologically, the airway lesion was characterized by
      prominent eosinophilic infiltrates, accompanied by mast cells, lymphocytes, and
      plasmacytes. The eosinophilic infiltrates were distributed throughout the airway:
      from trachea through respiratory bronchioles in the lung. The morphological
      feature of the lesion was indicative of an allergic airway disorder that can
      occur in humans with asthma. The present case is remarkable in that there is a
      paucity of reports on naturally occurring allergic airway disorders in nonhuman
      primates.

PMID- 20147586
TI  - Prospective randomised study to compare empirical treatment versus targeted
      treatment on the basis of the urine antigen results in hospitalised patients with
      community-acquired pneumonia.

PMID- 20147587
TI  - Stable breathing through deeper sleeping.

PMID- 20147588
TI  - Skeletal muscle dysfunction: a ubiquitous outcome in chronic disease?

PMID- 20147589
TI  - Acetaminophen and asthma.

PMID- 20147591
TI  - A 69-year-old smoker with mediastinal and hilar lymphadenopathy.

PMID- 20147592
TI  - Association between leukotriene receptor antagonist therapy and Churg-Strauss
      syndrome: an analysis of the FDA AERS database.
AB  - BACKGROUND: The possible role of leukotriene receptor antagonist (LTRA) therapy
      in the pathogenesis of Churg-Strauss syndrome (CSS) is uncertain. The aim was to
      examine the association between LTRA therapy and CSS in cases registered in the
      FDA Adverse Event Reporting System (AERS) database. METHODS: All cases of
      suspected drug-induced CSS reported to the AERS database between November 1997
      and April 2003 were reviewed. Subjects in whom LTRAs were the suspected
      medication and sufficient documentation existed to confirm the diagnosis of CSS
      were sequentially categorised into one of the following groups: (A) CSS before
      treatment initiation; (B) oral or inhaled corticosteroids reduced or stopped
      within 6 months of CSS onset; (C) possible prodromal phase of CSS at treatment
      initiation; (D) unstable asthma at treatment initiation; (E) stable asthma at
      treatment initiation. RESULTS: There were 181 case reports of suspected drug
      induced CSS with sufficient documentation to confirm a diagnosis of CSS; in 163
      (90%) an LTRA was a suspect medication. In 140 of these 163 cases there was
      sufficient documentation to sequentially categorize the case into groups, with 13
      (9%) in A, 27 (19%) in B, 11 (8%) in C, 28 (20%) in D and 61 (44%) in E.
      CONCLUSION: LTRA therapy was a suspect medication in most confirmed cases of CSS
      reported in the AERS database. In the majority of cases treated with an LTRA, CSS
      could not be explained by either corticosteroid withdrawal or pre-existing CSS.
      These findings are informative in considering the potential associations between
      LTRA therapy and CSS.

PMID- 20147594
TI  - Upper airway. 4: Sarcoidosis of the upper respiratory tract (SURT).
AB  - Sarcoidosis of the upper respiratory tract (SURT) includes nasopharyngeal,
      laryngeal and tracheal disease. Documented SURT occurs in approximately 5% of
      patients, although upper airway symptoms are more common in patients with
      sarcoidosis. Wegener granulomatosis may have a similar appearance to SURT, but
      there are important differences in the manifestations of the disease locally as
      well as systemically. In some cases, topical treatment is adequate to control
      SURT. However, many patients with significant sinus or laryngeal disease require
      long-term systemic treatment. While corticosteroids are often the initial drug of
      choice, there have been several reports of the effectiveness of cytotoxic agents
      and anti-tumour necrosis factor antibodies.

PMID- 20147597
TI  - Acute chest pain caused by pericardial fat necrosis.

PMID- 20147598
TI  - Detection of the ATPase activity of the molecular chaperones Hsp90 and Hsp72
      using the TranscreenerTM ADP assay kit.
AB  - The molecular chaperone heat shock protein 90 (Hsp90) is required for the correct
      folding and stability of a number of client proteins that are important for the
      growth and maintenance of cancer cells. Heat shock protein 72 (Hsp72), a co
      chaperone of Hsp90, is also emerging as an attractive cancer drug target. Both
      proteins bind and hydrolyze adenosine triphosphate (ATP), and ATPase activity is
      essential for their function. Inhibition of Hsp90 ATPase activity leads to the
      degradation of client proteins, resulting in cell growth inhibition and
      apoptosis. Several small-molecule inhibitors of the ATPase activity of Hsp90 have
      been described and are currently being evaluated clinically for the treatment of
      cancer. A number of methods for the measurement of ATPase activity have been
      previously used, but not all of these are ideally suited to screening cascades in
      drug discovery projects. The authors have evaluated the use of commercial
      reagents (Transcreener ADP) for the measurement of ATPase activity of both yeast
      and human Hsp90 (ATP K(m) approximately 500 microM) and human Hsp72 (ATP K(m) ~1
      microM). The low ATPase activity of human Hsp90 and its stimulation by the co
      chaperone Aha1 was measured with ease using reduced incubation times, generating
      robust data (Z' = 0.75). The potency of several small-molecule inhibitors of both
      Hsp90 and Hsp72 was determined using the Transcreener reagents and compared well
      to that determined using other assay formats.

PMID- 20147599
TI  - Contrasting two frameworks for ROC analysis of ordinal ratings.
AB  - BACKGROUND: Statistical evaluation of medical imaging tests used for diagnostic
      and prognostic purposes often employs receiver operating characteristic (ROC)
      curves. Two methods for ROC analysis are popular. The ordinal regression method
      is the standard approach used when evaluating tests with ordinal values. The
      direct ROC modeling method is a more recently developed approach, motivated by
      applications to tests with continuous values. OBJECTIVE: The authors compare the
      methods in terms of model formulations, interpretations of estimated parameters,
      the ranges of scientific questions that can be addressed with them, their
      computational algorithms, and the efficiencies with which they use data. RESULTS:
      The authors show that a strong relationship exists between the methods by
      demonstrating that they fit the same models when only a single test is evaluated.
      The ordinal regression models are typically alternative parameterizations of the
      direct ROC models and vice versa. The direct method has two major advantages over
      the ordinal regression method: 1) estimated parameters relate directly to ROC
      curves, facilitating interpretations of covariate effects on ROC performance, and
      2) comparisons between tests can be done directly in this framework. Comparisons
      can be made while accommodating covariate effects and even between tests that
      have values on different scales, such as between a continuous biomarker test and
      an ordinal valued imaging test. The ordinal regression method provides slightly
      more precise parameter estimates from data in our simulated data models.
      CONCLUSION: Although the ordinal regression method is slightly more efficient,
      the direct ROC modeling method has important advantages in regard to
      interpretation, and it offers a framework to address a broader range of
      scientific questions, including the facility to compare tests.

PMID- 20147600
TI  - Caregiver perspectives on transitions to assisted living and memory care.
AB  - This study describes family caregivers' experiences moving relatives with
      Alzheimer's disease or related disorders (ADRD) from their homes to assisted
      living facilities (ALFs) and subsequently to memory care units (MCUs). We also
      examined how these experiences differed between caregiver dyad types, such as
      adult children caring for parents. In-depth interviews with 15 caregivers were
      transcribed verbatim. Grounded theory identified themes. Constant comparative
      analysis compared experiences of caregiver dyads. Most caregivers recognized the
      likely need for future specialized care at the time of the move to the ALF, but
      did not recall receiving information about transfer policies. The ALF move was
      harder for spouses, the MCU move for adult children. Assisted living facilities
      can improve support for caregivers facing a relative's MCU transition through
      education about advantages of MCU placement and information about transfer
      policies. Support needs during transitions may differ between adult children and
      spouses.

PMID- 20147601
TI  - Discussing dementia-related behaviors during medical visits for people with
      Alzheimer's disease.
AB  - Research suggests that caregivers appreciate support from primary care physicians
      (PCPs) regarding dementia care; however, there remains a need for studies
      examining the role that PCPs play in behavior management. The purpose of this
      study was to quantitatively characterize the discussion on dementia-related
      behaviors (DRBs) during PCP visits and compare findings to an independently
      administered assessment of DRBs exhibited within a period of 4 weeks prior to the
      PCP visit. Twenty-five PCP visits of persons with dementia, in which caregivers
      coattended the visit, were audio-recorded and analyzed for occurrence of DRB
      discussion. Disruptive behaviors were reported by 80% of caregivers via
      independent assessment, yet discussed in 23% of medical visits. Dementia-related
      behavior discussion occurred in visits where caregivers independently reported
      significantly higher behavior frequency and behavior-related burden. Implications
      of findings for ways PCPs can assist the caregiver in behavior management are
      discussed.

PMID- 20147602
TI  - A qualitative assessment of the concept of dependence in Alzheimer's disease.
AB  - BACKGROUND: The Dependence Scale (DS) was designed to assess levels of patient
      need for care due to deficits typical of Alzheimer's disease (AD). This study
      examined content validity of the DS based on input from patients, caregivers, and
      clinicians. METHODS: Qualitative interviews with experts, patients, and
      caregivers were used to collect information on the concept of dependence and to
      assess content validity. RESULTS: Nine clinicians rated item relevance ''high''
      with consensus on the primacy of functional abilities and dependence in the
      measurement of AD progression. Twenty-two US, 11 UK, and 14 informal caregivers
      from Spain participated in focus groups; 18 patients participated in 3 separate
      focus groups. Discussion supported DS hierarchy of dependence, capture of mild-to
      severe dependence, suitability of response options, and short recall time frame.
      CONCLUSIONS: Clinicians, caregivers, and patients support content validity of the
      DS in mild-to-moderate AD. The DS may be valuable to capture dependence within
      future clinical dementia trials.

PMID- 20147603
TI  - Effects of atorvastatin 20 mg, rosuvastatin 10 mg, and atorvastatin/ezetimibe 5
      mg/5 mg on lipoproteins and glucose metabolism.
AB  - The aim of this study was to compare the effects of 3 different statin regimens
      that have equivalent low-density lipoprotein cholesterol (LDL-C) lowering
      efficacy on the apolipoprotein B/A1 ratio and glucose metabolism. After a 4-week
      dietary lead-in, 90 hypercholeserolemic patients were randomly assigned to 1 of 3
      treatment groups for 8 weeks: atorvastatin 20 mg, rosuvastatin 10 mg, or
      atorvastatin/ezetimibe 5 mg/5 mg. At drug treatment week 8, we compared the
      percentage changes in lipid parameters, apolipoprotein B/A1 ratio, hemoglobin
      A1c, and homeostasis model assessment-insulin resistance (HOMA-IR) from baseline.
      Seventy-six patients completed the study and the percentage changes in LDL-C were
      comparable among the groups. However, the percentage reduction in the
      apolipoprotein B/A1 ratio was significantly greater in the rosuvastatin group (
      47% +/- 14%, P = .04) and the combination group (-46% +/- 8%, P = .05) than in
      the atorvastatin group (-39% +/- 11%). The percentage increase in hemoglobin A1c
      was small but significantly greater in the atorvastatin group compared to the
      combination group (3.0% +/- 5.2% and -0.4% +/- 4.0%, P = .03). The effect of
      rosuvastatin on hemoglobin A1c was not different from those of the other 2
      regimens. The effects of 3 statin regimens were similar on HOMA-IR. In
      conclusion, 3 statin regimens have differential effect on apolipoprotein B/A1 and
      glycemic control after comparable LDL-C reduction.

PMID- 20147604
TI  - Response of cardiac sympathetic nerve activity to intravenous irbesartan in heart
      failure.
AB  - To determine the effect of irbesartan treatment on resting levels and arterial
      baroreflex control of cardiac sympathetic nerve activity (CSNA) in heart failure
      (HF), we studied conscious normal sheep and sheep with HF induced by rapid
      ventricular pacing for 8-10 wk (n = 7 per group). In HF, there is a large
      increase in CSNA that is detrimental to outcome. The causes of this increase in
      CSNA and the effect of angiotensin receptor blockers on CSNA in HF are unclear.
      CSNA, arterial blood pressure, heart rate (HR), and arterial baroreflex curves
      were recorded during a resting period and after 90 min of irbesartan infusion (12
      mg.kg(-1).h(-1) iv). This dose of irbesartan abolished the pressor response to
      intravenous ANG II infusion but caused only a slight decrease in the pressor
      response to centrally administered ANG II. In HF, there was a large increase in
      CSNA (from 44 +/- 3 to 87 +/- 3 bursts/100 heartbeats). Irbesartan reduced
      arterial pressure in the normal and HF groups, but the usual baroreflex-mediated
      increases in CSNA and HR were prevented. This resulted from a significant
      leftward shift in the CSNA and HR baroreflex curves in both groups. Irbesartan
      also decreased the sensitivity of the arterial baroreflex control of CSNA. Short
      term treatment with an angiotensin receptor blocker, at a dose that abolished the
      response to circulating, but not central, ANG II, prevented the reflex increase
      in CSNA in response to the drug-induced fall in arterial pressure.

PMID- 20147605
TI  - Effect of catecholamines on rat medullary thick ascending limb chloride
      transport: interaction with angiotensin II.
AB  - Previous studies have shown that in proximal and distal tubule nephron segments,
      peritubular ANG II stimulates sodium chloride transport. However, ANG II inhibits
      chloride transport in the medullary thick ascending limb (mTAL). Because ANG II
      and catecholamines are both stimulated by a decrease in extracellular fluid
      volume, the purpose of this study was to examine whether there was an interaction
      between ANG II and catecholamines to mitigate the inhibition in chloride
      transport by ANG II. In isolated perfused rat mTAL, 10(-8) M bath ANG II
      inhibited transport (from a basal transport rate of 165.6 +/- 58.8 to 58.8 +/-
      29.4 pmol.mm(-1).min(-1); P < 0.01). Bath norepinephrine stimulated chloride
      transport (from a basal transport rate of 298.1 +/- 31.7 to 425.2 +/- 45.8
      pmol.mm(-1).min(-1); P < 0.05) and completely prevented the inhibition in
      chloride transport by ANG II. The stimulation of chloride transport by
      norepinephrine was mediated entirely by its beta-adrenergic effect; however, both
      the beta- and alpha-adrenergic agonists isoproterenol and phenylephrine prevent
      the ANG II-mediated inhibition in chloride transport. In the presence of 10(-5) M
      propranolol, the effect of norepinephrine to prevent the inhibition of chloride
      transport by ANG II was still present. These data are consistent with an
      interaction of both alpha- and beta-catecholamines and ANG II on net chloride
      transport in the mTAL.

PMID- 20147606
TI  - Coupling-induced complexity in nephron models of renal blood flow regulation.
AB  - Tubular pressure and nephron blood flow time series display two interacting
      oscillations in rats with normal blood pressure. Tubuloglomerular feedback (TGF)
      senses NaCl concentration in tubular fluid at the macula densa, adjusts vascular
      resistance of the nephron's afferent arteriole, and generates the slower, larger
      amplitude oscillations (0.02-0.04 Hz). The faster smaller oscillations (0.1-0.2
      Hz) result from spontaneous contractions of vascular smooth muscle triggered by
      cyclic variations in membrane electrical potential. The two mechanisms interact
      in each nephron and combine to act as a high-pass filter, adjusting diameter of
      the afferent arteriole to limit changes of glomerular pressure caused by
      fluctuations of blood pressure. The oscillations become irregular in animals with
      chronic high blood pressure. TGF feedback gain is increased in hypertensive rats,
      leading to a stronger interaction between the two mechanisms. With a mathematical
      model that simulates tubular and arteriolar dynamics, we tested whether an
      increase in the interaction between TGF and the myogenic mechanism can cause the
      transition from periodic to irregular dynamics. A one-dimensional bifurcation
      analysis, using the coefficient that couples TGF and the myogenic mechanism as a
      bifurcation parameter, shows some regions with chaotic dynamics. With two
      nephrons coupled electrotonically, the chaotic regions become larger. The results
      support the hypothesis that increased oscillator interactions contribute to the
      transition to irregular fluctuations, especially when neighboring nephrons are
      coupled, which is the case in vivo.

PMID- 20147607
TI  - Dietary fructose accelerates the development of diabetes in UCD-T2DM rats:
      amelioration by the antioxidant, alpha-lipoic acid.
AB  - Sustained fructose consumption has been shown to induce insulin resistance and
      glucose intolerance, in part, by promoting oxidative stress. Alpha-lipoic acid
      (LA) is an antioxidant with insulin-sensitizing activity. The effect of sustained
      fructose consumption (20% of energy) on the development of T2DM and the effects
      of daily LA supplementation in fructose-fed University of California, Davis-Type
      2 diabetes mellitus (UCD-T2DM) rats, a model of polygenic obese T2DM, was
      investigated. At 2 mo of age, animals were divided into three groups: control,
      fructose, and fructose + LA (80 mg LA.kg body wt(-1).day(-1)). One subset was
      followed until diabetes onset, while another subset was euthanized at 4 mo of age
      for tissue collection. Monthly fasted blood samples were collected, and an
      intravenous glucose tolerance test (IVGTT) was performed. Fructose feeding
      accelerated diabetes onset by 2.6 +/- 0.5 mo compared with control (P < 0.01),
      without affecting body weight. LA supplementation delayed diabetes onset in
      fructose-fed animals by 1.0 +/- 0.7 mo (P < 0.05). Fructose consumption lowered
      the GSH/GSSG ratio, while LA attenuated the fructose-induced decrease of
      oxidative capacity. Insulin sensitivity, as assessed by IVGTT, decreased in both
      fructose-fed and fructose + LA-supplemented rats. However, glucose excursions in
      fructose-fed LA-supplemented animals were normalized to those of control via
      increased glucose-stimulated insulin secretion. Fasting plasma triglycerides were
      twofold higher in fructose-fed compared with control animals at 4 mo, and
      triglyceride exposure during IVGTT was increased in both the fructose and
      fructose + LA groups compared with control. In conclusion, dietary fructose
      accelerates the onset of T2DM in UCD-T2DM rats, and LA ameliorates the effects of
      fructose by improving glucose homeostasis, possibly by preserving beta-cell
      function.

PMID- 20147608
TI  - Effects of glucagon-like peptide 1 and oxyntomodulin on neuronal activity of
      ghrelin-sensitive neurons in the hypothalamic arcuate nucleus.
AB  - Glucagon-like peptide 1 (GLP-1) and oxyntomodulin (OXM) are structurally related
      gastrointestinal hormones that are secreted in response to food intake. They
      reduce food intake and body weight and exert partly overlapping actions on
      glucose homeostasis and gastrointestinal function. The hypothalamic arcuate (ARC)
      nucleus is among the central structures expressing a high density of GLP-1
      receptors (GLP-1R), which are known to be activated by both peptides. It was the
      aim of our electrophysiological studies to characterize the effects of GLP-1 and
      OXM on functionally defined ghrelin-sensitive ARC neurons. GLP-1 and OXM (10(-7)
      M) exerted excitatory effects in about two-thirds of ghrelin-inhibited neurons
      and in approximately one-third of ghrelin-excited cells. In addition, a minor
      fraction of the ghrelin-excited cells was inhibited by both peptides. There was a
      high degree of cosensitivity to GLP-1 and OXM, and the effects of both hormones
      were blocked by the GLP-1R antagonist exendin(9-39). The GLP-1R-mediated
      excitations and inhibitions persisted under synaptic blockade, indicating a
      direct postsynaptic mode of action. Our results demonstrate that GLP-1 and OXM
      directly and similarly alter neuronal activity in the ARC, probably via a common
      GLP-1R-mediated mechanism. Ghrelin-antagonistic effects on neuronal activity,
      which might be implicated in ghrelin-antagonistic in vivo actions, resulting from
      GLP-1R stimulation (e.g., GLP-1R dependent supression of food intake),
      predominated in ghrelin-inhibited ARC neurons. However, a subset of ghrelin
      excited ARC neurons showed responses to OXM or GLP-1, suggesting the existence of
      a common mode of action for these hormones; the functional relevance of this
      effect remains to be elucidated.

PMID- 20147609
TI  - Lymphocyte responses exacerbate angiotensin II-dependent hypertension.
AB  - Activation of the immune system by ANG II contributes to the pathogenesis of
      hypertension, and pharmacological suppression of lymphocyte responses can
      ameliorate hypertensive end-organ damage. Therefore, to examine the mechanisms
      through which lymphocytes mediate blood pressure elevation, we studied ANG II
      dependent hypertension in scid mice lacking lymphocyte responses and wild-type
      controls. Scid mice had a blunted hypertensive response to chronic ANG II
      infusion and accordingly developed less cardiac hypertrophy. Moreover, lymphocyte
      deficiency led to significant reductions in heart and kidney injury following 4
      wk of angiotensin. The muted hypertensive response in the scid mice was
      associated with increased sodium excretion, urine volumes, and weight loss
      beginning on day 5 of angiotensin infusion. To explore the mechanisms underlying
      alterations in blood pressure and renal sodium handling, we measured gene
      expression for vasoactive mediators in the kidney after 4 wk of ANG II
      administration. Scid mice and controls had similar renal expression for
      interferon-gamma, interleukin-1beta, and interleukin-6. By contrast, lymphocyte
      deficiency (i.e., scid mice) during ANG II infusion led to upregulation of tumor
      necrosis factor-alpha, endothelial nitric oxide synthase (eNOS), and
      cyclooxygenase-2 (COX-2) in the kidney. In turn, this enhanced eNOS and COX-2
      expression in the scid kidneys was associated with exaggerated renal generation
      of nitric oxide, prostaglandin E(2), and prostacyclin, all of which promote
      natriuresis. Thus, the absence of lymphocyte activity protects from hypertension
      by allowing blood pressure-induced sodium excretion, possibly via stimulation of
      eNOS- and COX-2-dependent pathways.

PMID- 20147610
TI  - Urinary tract obstruction induces transient accumulation of COX-2-derived
      prostanoids in kidney tissue.
AB  - Inhibitors of cyclooxygenase (COX)-2 prevent suppression of aquaporin-2 and
      reduce polyuria in the acute phase after release of bilateral ureteral
      obstruction (BUO). We hypothesized that BUO leads to COX-2-mediated local
      accumulation of prostanoids in inner medulla (IM) tissue. To test this, rats were
      subjected to BUO and treated with selective COX-1 or COX-2 inhibitors. Tissue was
      examined at 2, 6, 12, and 24 h after BUO. COX-2 protein abundance increased in IM
      12 and 24 h after onset of BUO but did not change in cortex. COX-1 did not change
      at any time points in any region. A full profile of all five primary prostanoids
      was obtained by mass spectrometric determination of PGE(2), PGF(2alpha), 6-keto
      PGF(1alpha), PGD(2), and thromboxane (Tx) B(2) concentrations in kidney
      cortex/outer medulla and IM fractions. IM concentration of PGE(2), 6-keto
      PGF(1alpha), and PGF(2alpha) was increased at 6 h BUO, and PGE(2) and PGF(2alpha)
      increased further at 12 h BUO. TxB(2) increased after 12 h BUO. 6-keto
      PGF(1alpha) remained significantly increased after 24 h BUO. The COX-2 inhibitor
      parecoxib lowered IM PGE(2,) TxB(2), 6-keto-PGF(1alpha), and PGF(2alpha) below
      vehicle-treated BUO and sham rats at 6, 12 and, 24 h BUO. The COX-1 inhibitor SC
      560 lowered PGE(2), PGF(2alpha), and PGD(2) in IM compared with untreated 12 h
      BUO, but levels remained significantly above sham. In cortex tissue, PGE(2) and 6
      keto-PGF(1alpha) concentrations were elevated at 6 h only. In conclusion, COX-2
      activity contributes to the transient increase in prostacyclin metabolite 6-keto
      PGF(1alpha) and TxB(2) concentration in the kidney IM, and COX-2 is the
      predominant isoform that is responsible for accumulation of PGE(2) and
      PGF(2alpha) with minor, but significant, contributions from COX-1. PGD(2)
      synthesis is mediated exclusively by COX-1. In BUO, therapeutic interventions
      aimed at the COX-prostanoid pathway should target primarily COX-2.

PMID- 20147611
TI  - T lymphocytes mediate hypertension and kidney damage in Dahl salt-sensitive rats.
AB  - This study examined mechanisms by which immune cells participate in the
      development of hypertension and renal disease in Dahl salt-sensitive (SS) rats.
      Increasing dietary salt from 0.4% to 4.0% NaCl significantly increased renal
      infiltration of T lymphocytes from 8.8 +/- 1.2 x 10(5) to 14.4 +/- 2.0 x 10(5)
      cells/2 kidneys, increased arterial blood pressure from 131 +/- 2 to 165 +/- 6
      mmHg, increased albumin excretion rate from 17 +/- 3 to 129 +/- 20 mg/day, and
      resulted in renal glomerular and tubular damage. Furthermore, renal tissue ANG II
      was not suppressed in the kidneys of SS rats fed 4.0% NaCl. Administration of the
      immunosuppressive agent mycophenolate mofetil (MMF; 20 mg.kg(-1).day(-1))
      prevented the infiltration of T lymphocytes and attenuated Dahl SS hypertension
      and renal disease. In contrast to vehicle-treated rats, Dahl SS rats administered
      MMF demonstrated a suppression of renal tissue ANG II from 163 +/- 26 to 88 +/- 9
      pg/g of tissue when fed high salt. Finally, it was demonstrated that the T
      lymphocytes isolated from the kidney possess renin and angiotensin-converting
      enzyme activity. These data indicate that infiltrating T cells are capable of
      participating in the production of ANG II and are associated with increased
      intrarenal ANG II, hypertension, and renal disease. The suppression of T-cell
      infiltration decreased intrarenal ANG II and prevented Dahl SS hypertension and
      kidney damage. As such, infiltrating cells are capable of participating in the
      established phase of Dahl SS hypertension.

PMID- 20147612
TI  - Nitric oxide produced by endothelial nitric oxide synthase promotes diuresis.
AB  - Extracellular fluid volume is highly regulated, at least in part, by peripheral
      resistance and renal function. Nitric oxide (NO) produced by NO synthase type 3
      (NOS 3) in the nonrenal vasculature may promote fluid retention by reducing
      systemic vascular resistance and arterial pressure. In contrast, NO produced by
      renal NOS 3 promotes water excretion by reducing renal vascular resistance,
      increasing glomerular filtration, and inhibiting reabsorption along the nephron.
      Thus, the net effect of NO from NOS 3 on urinary volume (UV) is unclear. We
      hypothesized that NO produced by NOS 3 promotes water excretion primarily due to
      renal tubular effects. We gave conscious wild-type and NOS 3 -/- mice an acute
      volume load and measured UV, blood pressure, plasma renin concentration (PRC),
      Na(+), vasopressin, and urinary Na(+) and creatinine concentrations. To give the
      acute volume load, we trained mice to drink a large volume of water while in
      metabolic cages. On the day of the experiment, water was replaced with 1%
      sucrose, and mice had access to it for 1 h. Volume intake was similar in both
      groups. Over 3 h, wild-type mice excreted 62 +/- 10% of the volume load, but NOS
      3 -/- excreted only 42 +/- 5% (P < 0.05). Blood pressure in NOS 3 -/- was 118 +/-
      3 compared with 110 +/- 2 mmHg in wild-type mice (P < 0.05), but it did not
      change following volume load in either strain. PRC, vasopressin, and glomerular
      filtration rate were similar between groups. Urinary Na(+) excretion was 49.3 +/-
      7.0 in wild-type vs. 37.8 +/- 6.4 mumol/3 h in NOS 3 -/- mice (P < 0.05).
      Bumetanide administration eliminated the difference in volume excretion between
      wild-type and NOS 3 -/- mice. We conclude that 1) NO produced by NOS 3 promotes
      water and Na(+) excretion and 2) the renal epithelial actions of NO produced by
      NOS 3 supersede the systemic and renal vascular actions.

PMID- 20147614
TI  - Structure elucidation and biological activity of the oversulfated chondroitin
      sulfate contaminant in Baxter heparin.
AB  - From late December 2007 to February 2008, the number of adverse responses to
      heparin infusions rose noticeably above baseline levels in North America,
      ultimately resulting in a widespread recall of all heparin vial products made by
      Baxter Healthcare. Using various analytical techniques and the de novo synthesis
      of a fully sulfated chondroitin sulfate (FSCS) derivative, the authors have
      confirmed the identity of the contaminant as an oversulfated chondroitin sulfate
      (OSCS) and have also defined the heterogeneity and concentration of this
      contaminant in various lots of heparin. Using both contaminated heparin products
      and the synthetically produced derivative, the authors have shown that the OSCS
      produces a dose-dependent hypotension in both pigs and rats and that the response
      in rats can be abrogated with bradyzide, a rodent-selective B(2) bradykinin
      receptor antagonist. The no observed effect level (NOEL) for this contaminant
      appears to be approximately 1 mg/kg, corresponding to a contamination level in
      finished lots of heparin of approximately 3%. Using human plasma, the OSCS
      derivative was shown to activate kallikrein. These data provide insight into the
      etiology of the adverse events, particularly refractory hypotension, observed in
      patients who were exposed to heparin contaminated with OSCS.

PMID- 20147613
TI  - The effect of acid reduction with a proton pump inhibitor on the pharmacokinetics
      of lopinavir or ritonavir in HIV-infected patients on lopinavir/ritonavir-based
      therapy.

PMID- 20147615
TI  - Population pharmacokinetics and pharmacogenetics of mycophenolic acid following
      administration of mycophenolate mofetil in de novo pediatric renal-transplant
      patients.
AB  - The objective was to develop a population pharmacokinetic-pharmacogenetic model
      of mycophenolic acid following administration of mycophenolate mofetil (MMF) in
      de novo pediatric renal-transplant patients and identify factors that explain
      variability. The pharmacokinetic samples were collected from 89 de novo pediatric
      renal-transplant patients treated with MMF and studied during the first 60
      postoperative days. All patients were genotyped for UGT1A8-A9, UGT2B7, and ABCC2.
      Population pharmacokinetic analysis was performed with the NONMEM and was
      validated using bootstrap visual predictive check. The pharmacokinetic data were
      best described by a 2-compartment model with Erlang distribution to describe the
      absorption phase. The covariate analysis identified body weight as an individual
      factor influencing central volume of distribution and concomitant
      immunosuppressive medication and identified body weight and UGT2B7 802C>T
      genotype as individual factors influencing apparent oral clearance (CL/F) of MMF.
      CL/F in cyclosporine-MMF-treated patients was 33% higher than in tacrolimus-MMF
      treated patients. The CL/F was significantly lower in patients with UGT2B7 802
      C/C genotype compared with patients with UGT2B7 802 C/T and 802T/T genotypes, and
      this effect was independent of concomitant immunosuppressive medication or body
      weight. The population pharmacokinetic-pharmacogenetic model of mycophenolic acid
      was validated. Body weight, concomitant medication, and UGT2B7 genotype
      contribute significantly to the interindividual variability of MMF disposition in
      pediatric renal-transplant patients.

PMID- 20147616
TI  - Pharmacokinetics and antibody responses to the CD3 antibody otelixizumab used in
      the treatment of type 1 diabetes.
AB  - Otelixizumab is a chimeric CD3 antibody that has been genetically engineered to
      remove the glycosylation site in the Fc domain. This limits its ability to bind
      to complement or Fc receptors and reduces the risk of adverse clinical reactions
      due to cytokine release. In a trial for treatment of type 1 diabetes, a short
      treatment with otelixizumab resulted in a reduced requirement for insulin lasting
      at least 18 months. In the course of this trial, the blood concentrations of the
      antibody were measured by flow cytometry to determine its pharmacokinetic
      profile. Dose-dependent accumulation of otelixizumab was demonstrated and
      modeling of the data indicated that the terminal half-life was approximately 1.5
      days. Antibody responses to otelixizumab were measured by 2 methods: a bridging
      enzyme-linked immunosorbent assay and surface plasmon resonance. The surface
      plasmon resonance method had a greater sensitivity and was able to detect
      responses in all patients, starting at 8 days after the commencement of therapy.
      Neutralizing antibodies were detected in a significant proportion of patients by
      days 22 to 29. Although no adverse clinical effects were associated with these
      antibody responses and they did not appear to affect the clearance of the drug,
      they might have important implications for possible retreatment of the patients.

PMID- 20147617
TI  - Correlation of inhibition of platelet aggregation with cardiovascular and
      bleeding outcomes in acute coronary syndromes.
AB  - Inhibition of platelet aggregation (IPA) has been a drug development target in
      acute coronary syndrome (ACS) for almost 2 decades. The relationship between IPA
      and cardiovascular (CV) events has not been quantified. Cardiovascular (non fatal
      myocardial infarction, death) and major bleeding events were extracted from phase
      2 or 3 randomized, double-blind trials that evaluated oral and intravenous
      glycoprotein 2b/3a (GP2b/3a) antagonists and thienopyridines. IPA was extracted
      from different sources that studied a similar regimen in a similar population.
      Events were correlated to IPA using a linear relative-risk mixed-effects model.
      Covariates included type of drug, mean age, gender percentage, and ADP. Clinical
      trial simulations were conducted to evaluate the relationship between IPA and the
      likelihood of observing a CV event in a 6-month end point trial. Data from 81918
      subjects in 20 studies were extracted from the literature. To achieve a 20%
      relative reduction in CV events would require a further 77% (56%-100%) absolute
      increase in IPA for IV GP2b/3a antagonists or a further 27%(20%-41%) absolute
      increase for thienopyridines. CV risk reduction was less in studies with older
      subjects and greater in studies with greater percentages of male subjects.
      Assuming a 3% major bleeding rate in the control group, these drugs had a 1%
      increase in absolute risk as absolute platelet inhibition increases by 60%
      (range, 40%-80%). This relationship in intrinsic bleeding may be different in
      different population subtypes. Assuming a 12% event rate, a 6-month active
      controlled thienopyridine trial with 3000 subjects could detect a relationship
      between CV events and IPA with 80% likelihood. Target IPA increases in ACS are an
      absolute increase of 80% for IV GP2b/3a antagonists and 30% for thienopyridines.
      Quantitative models using literature data on IPA and CV events can be used to
      select dose regimens in early stages of drug development.

PMID- 20147618
TI  - Clinical pharmacokinetics of pregabalin in healthy volunteers.
AB  - Pregabalin has shown clinical efficacy for treatment of neuropathic pain
      syndromes, partial seizures, and anxiety disorders. Five studies in healthy
      volunteers are performed to investigate single- and multiple-dose
      pharmacokinetics of pregabalin. Pregabalin is rapidly absorbed following oral
      administration, with peak plasma concentrations occurring between 0.7 and 1.3
      hours. Pregabalin oral bioavailability is approximately 90% and is independent of
      dose and frequency of administration. Food reduces the rate of pregabalin
      absorption, resulting in lower and delayed maximum plasma concentrations, yet the
      extent of drug absorption is unaffected, suggesting that pregabalin may be
      administered without regard to meals. Pregabalin elimination half-life is
      approximately 6 hours and steady state is achieved within 1 to 2 days of repeated
      administration. Corrected for oral bioavailability, pregabalin plasma clearance
      is essentially equivalent to renal clearance, indicating that pregabalin
      undergoes negligible nonrenal elimination. Pregabalin demonstrates desirable,
      predictable pharmacokinetic properties that suggest ease of use. Because
      pregabalin is eliminated renally, renal function affects its pharmacokinetics.

PMID- 20147619
TI  - Markov random fields reveal an N-terminal double beta-propeller motif as part of
      a bacterial hybrid two-component sensor system.
AB  - The recent explosion in newly sequenced bacterial genomes is outpacing the
      capacity of researchers to try to assign functional annotation to all the new
      proteins. Hence, computational methods that can help predict structural motifs
      provide increasingly important clues in helping to determine how these proteins
      might function. We introduce a Markov Random Field approach tailored for
      recognizing proteins that fold into mainly beta-structural motifs, and apply it
      to build recognizers for the beta-propeller shapes. As an application, we
      identify a potential class of hybrid two-component sensor proteins, that we
      predict contain a double-propeller domain.

PMID- 20147620
TI  - Morphine peripheral analgesia depends on activation of the
      PI3Kgamma/AKT/nNOS/NO/KATP signaling pathway.
AB  - Morphine is one of the most prescribed and effective drugs used for the treatment
      of acute and chronic pain conditions. In addition to its central effects,
      morphine can also produce peripheral analgesia. However, the mechanisms
      underlying this peripheral action of morphine have not yet been fully elucidated.
      Here, we show that the peripheral antinociceptive effect of morphine is lost in
      neuronal nitric-oxide synthase null mice and that morphine induces the production
      of nitric oxide in primary nociceptive neurons. The activation of the nitric
      oxide pathway by morphine was dependent on an initial stimulation of
      PI3Kgamma/AKT protein kinase B (AKT) and culminated in increased activation of
      K(ATP) channels. In the latter, this intracellular signaling pathway might cause
      a hyperpolarization of nociceptive neurons, and it is fundamental for the direct
      blockade of inflammatory pain by morphine. This understanding offers new targets
      for analgesic drug development.

PMID- 20147621
TI  - Communication via gap junctions underlies early functional and beneficial
      interactions between grafted neural stem cells and the host.
AB  - How grafted neural stem cells (NSCs) and their progeny integrate into recipient
      brain tissue and functionally interact with host cells is as yet unanswered. We
      report that, in organotypic slice cultures analyzed by ratiometric time-lapse
      calcium imaging, current-clamp recordings, and dye-coupling methods, an early and
      essential way in which grafted murine or human NSCs integrate functionally into
      host neural circuitry and affect host cells is via gap-junctional coupling, even
      before electrophysiologically mature neuronal differentiation. The gap junctions,
      which are established rapidly, permit exogenous NSCs to influence directly host
      network activity, including synchronized calcium transients with host cells in
      fluctuating networks. The exogenous NSCs also protect host neurons from death and
      reduce such signs of secondary injury as reactive astrogliosis. To determine
      whether gap junctions between NSCs and host cells may also mediate
      neuroprotection in vivo, we examined NSC transplantation in two murine models
      characterized by degeneration of the same cell type (Purkinje neurons) from
      different etiologies, namely, the nervous and SCA1 mutants. In both, gap
      junctions (containing connexin 43) formed between NSCs and host cells at risk,
      and were associated with rescue of neurons and behavior (when implantation was
      performed before overt neuron loss). Both in vitro and in vivo beneficial NSC
      effects were abrogated when gap junction formation or function was suppressed by
      pharmacologic and/or RNA-inhibition strategies, supporting the pivotal mediation
      by gap-junctional coupling of some modulatory, homeostatic, and protective
      actions on host systems as well as establishing a template for the subsequent
      development of electrochemical synaptic intercellular communication.

PMID- 20147622
TI  - A model for the CO-inhibited form of [NiFe] hydrogenase: synthesis of CO3Fe(micro
      StBu)3Ni{SC6H3-2,6-(mesityl)2} and reversible CO addition at the Ni site.
AB  - A [NiFe] hydrogenase model compound having a distorted trigonal-pyramidal nickel
      center, (CO)(3)Fe(micro-S(t)Bu)(3)Ni(SDmp), 1 (Dmp = C(6)H(3)-2,6-(mesityl)(2)),
      was synthesized from the reaction of the tetranuclear Fe-Ni-Ni-Fe complex
      [(CO)(3)Fe(micro-S(t)Bu)(3)Ni](2)(micro-Br)(2), 2 with NaSDmp at -40 degrees C.
      The nickel site of complex 1 was found to add CO or CN(t)Bu at -40 degrees C to
      give (CO)(3)Fe(S(t)Bu)(micro-S(t)Bu)(2)Ni(CO)(SDmp), 3, or
      (CO)(3)Fe(S(t)Bu)(micro-S(t)Bu)(2)Ni(CN(t)Bu)(SDmp), 4, respectively. One of the
      CO bands of 3, appearing at 2055 cm(-1) in the infrared spectrum, was assigned as
      the Ni-CO band, and this frequency is comparable to those observed for the CO
      inhibited forms of [NiFe] hydrogenase. Like the CO-inhibited forms of [NiFe]
      hydrogenase, the coordination of CO at the nickel site of 1 is reversible, while
      the CN(t)Bu adduct 4 is more robust.

PMID- 20147623
TI  - Insight into the mechanism of an iron dioxygenase by resolution of steps
      following the FeIV=HO species.
AB  - Iron oxygenases generate elusive transient oxygen species to catalyze substrate
      oxygenation in a wide range of metabolic processes. Here we resolve the reaction
      sequence and structures of such intermediates for the archetypal non-heme Fe(II)
      and alpha-ketoglutarate-dependent dioxygenase TauD. Time-resolved Raman spectra
      of the initial species with (16)O(18)O oxygen unequivocally establish the Fe(IV)
      horizontal lineO structure. (1)H/(2)H substitution reveals direct interaction
      between the oxo group and the C1 proton of substrate taurine. Two new transient
      species were resolved following Fe(IV) horizontal lineO; one is assigned to the
      nu(FeO) mode of an Fe(III) horizontal line O(H) species, and a second is likely
      to arise from the vibration of a metal-coordinated oxygenated product, such as
      Fe(II) horizontal line O horizontal line C(1) or Fe(II) horizontal line OOCR.
      These results provide direct insight into the mechanism of substrate oxygenation
      and suggest an alternative to the hydroxyl radical rebinding paradigm.

PMID- 20147624
TI  - Electrostatics of aquaporin and aquaglyceroporin channels correlates with their
      transport selectivity.
AB  - Aquaporins are homotetrameric channel proteins, which allow the diffusion of
      water and small solutes across biological membranes. According to their transport
      function, aquaporins can be divided into "orthodox aquaporins", which allow the
      flux of water molecules only, and "aquaglyceroporins", which facilitate the
      diffusion of glycerol and other small solutes in addition to water. The
      contribution of individual residues in the pore to the selectivity of orthodox
      aquaporins and aquaglyceroporins is not yet fully understood. To gain insights
      into aquaporin selectivity, we focused on the sequence variation and
      electrostatics of their channels. The continuum Poisson-Boltzmann electrostatic
      potential along the channel was calculated and compared for ten three-dimensional
      structures which are representatives of different aquaporin subfamilies, and a
      panel of functionally characterized mutants, for which high-accuracy three
      dimensional-models could be derived. Interestingly, specific electrostatic
      profiles associated with the main selectivity to water or glycerol could be
      identified. In particular: (i) orthodox aquaporins showed a distinctive
      electrostatic potential maximum at the periplasmic side of the channel around the
      aromatic/Arg (ar/R) constriction site; (ii) aquaporin-0 (AQP0), a mammalian
      aquaporin with considerably low water permeability, had an additional deep
      minimum at the cytoplasmic side; (iii) aquaglyceroporins showed a rather flat
      potential all along the channel; and (iv) the bifunctional protozoan PfAQP had an
      unusual all negative profile. Evaluation of electrostatics of the mutants, along
      with a thorough sequence analysis of the aquaporin pore-lining residues,
      illuminated the contribution of specific residues to the electrostatics of the
      channels and possibly to their selectivity.

PMID- 20147625
TI  - Quantitative study of synthetic Hox transcription factor-DNA interactions in live
      cells.
AB  - Transcription factor-DNA interactions are life sustaining and therefore the
      subject of intensive research. In spite of vast effort, quantitative in vivo
      studies of the molecular mechanisms underlying these fundamental interactions
      remain challenging. In the preceding paper, we designed synthetic Sex combs
      reduced (Scr) peptides and validated genetically their function as
      transcriptional regulators. Here we present a controllable system for
      quantitative studies of protein-DNA interactions in live cells that enables us to
      "titrate" the concentration of the synthetic Scr peptides in a single cell. Using
      methods with single-molecule sensitivity, advanced fluorescence imaging and
      fluorescence correlation spectroscopy (FCS), we were able to study the kinetics
      of Scr-DNA interactions in live salivary gland cells, where Scr is normally
      expressed during development. We discerned freely moving Scr molecules,
      characterized the specific and nonspecific Scr peptide-DNA interactions, and
      estimated their corresponding dissociation constants (K(d)) in vivo. Our results
      suggest that the synthetic Scr transcription factors find their specific target
      sites primarily by multiple association/dissociation events, the rapidity of
      which is largely owed to electrostatic interactions. Based on these new findings,
      we formulate a model mechanism and emulate the kinetics of Scr homeodomain-DNA
      interactions in live cells using numerical simulations.

PMID- 20147627
TI  - Laboratory study of selected personal inhalable aerosol samplers.
AB  - Assessment of inhalable dust exposure requires reliable sampling methods in order
      to measure airborne inhalable particles' concentrations. Many inhalable aerosol
      samplers can be used but their performances widely vary and remain unknown in
      some cases. The sampling performance of inhalable samplers is strongly dependent
      on particle size and ambient air velocity. Five inhalable aerosol samplers have
      been studied in two laboratory wind tunnels using polydisperse glass-beads' test
      aerosol. Samplers tested were IOM sampler (UK), two versions of CIP 10-I sampler,
      v1 and v2 (F), 37-mm closed face cassette sampler (USA), 37-mm cassette fitted up
      with an ACCU-CAP insert (USA), and Button sampler (USA). Particle size-dependent
      sampling efficiencies were measured in a horizontal wind tunnel under a 1 m s(-1)
      wind velocity and in a vertical tunnel under calm air, using a specific method
      with Coulter(R) counter particle size number distribution determinations.
      Compared with CEN-ISO-ACGIH sampling criteria for inhalable dust, the
      experimental results show fairly high sampling efficiency for the IOM and CIP 10
      I v2 samplers and slightly lower efficiencies for the Button and CIP 10-I v1
      samplers. The closed face cassette (4-mm orifice) produced the poorest
      performances of all the tested samplers. This can be improved by using the ACCU
      CAP internal capsule, which prevents inner wall losses inside the cassette.
      Significant differences between moving air and calm air sampling efficiency were
      observed for all the studied samplers.

PMID- 20147626
TI  - Function and specificity of synthetic Hox transcription factors in vivo.
AB  - Homeotic (Hox) genes encode transcription factors that confer segmental identity
      along the anteroposterior axis of the embryo. However the molecular mechanisms
      underlying Hox-mediated transcription and the differential requirements for
      specificity in the regulation of the vast number of Hox-target genes remain ill
      defined. Here we show that synthetic Sex combs reduced (Scr) genes that encode
      the Scr C terminus containing the homedomain (HD) and YPWM motif (Scr-HD) are
      functional in vivo. Synthetic Scr-HD peptides can induce ectopic salivary glands
      in the embryo and homeotic transformations in the adult fly, act as
      transcriptional activators and repressors during development, and participate in
      protein-protein interactions. Their transformation capacity was found to be
      enhanced over their full-length counterpart and mutations known to transform the
      full-length protein into constitutively active or inactive variants behaved
      accordingly in the synthetic peptides. Our results show that synthetic Scr-HD
      genes are sufficient for homeotic function in Drosophila and suggest that the N
      terminus of Scr has a role in transcriptional potency, rather than specificity.
      We also demonstrate that synthetic peptides behave largely in a predictable way,
      by exhibiting Scr-specific phenotypes throughout development, which makes them an
      important tool for synthetic biology.

PMID- 20147628
TI  - Chemokine scavenger D6 is expressed by trophoblasts and aids the survival of
      mouse embryos transferred into allogeneic recipients.
AB  - Proinflammatory CC chemokines are thought to drive recruitment of maternal
      leukocytes into gestational tissues and regulate extravillous trophoblast
      migration. The atypical chemokine receptor D6 binds many of these chemokines and
      is highly expressed by the human placenta. D6 is thought to act as a chemokine
      scavenger because, when ectopically expressed in cell lines in vitro, it
      efficiently internalizes proinflammatory CC chemokines and targets them for
      destruction in the absence of detectable chemokine-induced signaling. Moreover,
      D6 suppresses inflammation in many mouse tissues, and notably, D6-deficient
      fetuses in D6-deficient female mice show increased susceptibility to inflammation
      driven resorption. In this paper, we report strong anti-D6 immunoreactivity, with
      specific intracellular distribution patterns, in trophoblast-derived cells in
      human placenta, decidua, and gestational membranes throughout pregnancy and in
      trophoblast disease states of hydatidiform mole and choriocarcinoma. We show, for
      the first time, that endogenous D6 in a human choriocarcinoma-derived cell line
      can mediate progressive chemokine scavenging and that the D6 ligand CCL2 can
      specifically associate with human syncytiotrophoblasts in term placenta in situ.
      Moreover, despite strong chemokine production by gestational tissues, levels of
      D6-binding chemokines in maternal plasma decrease during pregnancy, even in women
      with pre-eclampsia, a disease associated with increased maternal inflammation. In
      mice, D6 is not required for syngeneic or semiallogeneic fetal survival in
      unchallenged mice, but interestingly, it does suppress fetal resorption after
      embryo transfer into fully allogeneic recipients. These data support the view
      that trophoblast D6 scavenges maternal chemokines at the fetomaternal interface
      and that, in some circumstances, this can help to ensure fetal survival.

PMID- 20147629
TI  - Dendritic cells derived from hemozoin-loaded monocytes display a partial
      maturation phenotype that promotes HIV-1 trans-infection of CD4+ T cells and
      virus replication.
AB  - Coinfection of HIV-1 patients with Plasmodium falciparum, the etiological agent
      of malaria, results in a raise of viral load and an acceleration of disease
      progression. The primary objective of this study was to investigate whether the
      malarial pigment hemozoin (HZ), a heme by-product of hemoglobin digestion by
      malaria parasites, can affect HIV-1 transmission by monocytes-derived dendritic
      cells (DCs) to CD4(+) T cells when HZ is initially internalized in monocytes
      before their differentiation in DCs. We demonstrate in this study that HZ
      treatment during the differentiation process induces an intermediate maturation
      phenotype when compared with immature and fully mature DCs. Furthermore, the DC
      mediated transfer of HIV-1 is enhanced in presence of HZ, a phenomenon that may
      be linked with the capacity of HZ-loaded cells to interact and activate CD4(+) T
      cells. Altogether our findings suggest a new mechanism that could partially
      explain the increased HIV-1 virus production during a coinfection with P.
      falciparum. Understanding the multifaceted interactions between P. falciparum and
      HIV-1 is an important challenge that could lead to the development of new
      treatment strategies.

PMID- 20147630
TI  - The human IL-3/granulocyte-macrophage colony-stimulating factor locus is
      epigenetically silent in immature thymocytes and is progressively activated
      during T cell development.
AB  - The closely linked IL-3 and GM-CSF genes are located within a cluster of cytokine
      genes co-expressed in activated T cells. Their activation in response to TCR
      signaling pathways is controlled by specific, inducible upstream enhancers. To
      study the developmental regulation of this locus in T lineage cells, we created a
      transgenic mouse model encompassing the human IL-3 and GM-CSF genes plus the
      known enhancers. We demonstrated that the IL-3/GM-CSF locus undergoes progressive
      stages of activation, with stepwise increases in active modifications and the
      proportion of cytokine-expressing cells, throughout the course of T cell
      differentiation. Looking first at immature cells, we found that the IL-3/GM-CSF
      locus was epigenetically silent in CD4/CD8 double positive thymocytes, thereby
      minimizing the potential for inappropriate activation during the course of TCR
      selection. Furthermore, we demonstrated that the locus did not reach its maximal
      transcriptional potential until after T cells had undergone blast cell
      transformation to become fully activated proliferating T cells. Inducible locus
      activation in mature T cells was accompanied by noncoding transcription
      initiating within the enhancer elements. Significantly, we also found that memory
      CD4 positive T cells, but not naive T cells, maintain a remodeled chromatin
      structure resembling that seen in T blast cells.

PMID- 20147631
TI  - Neisseria gonorrhoeae enhances HIV-1 infection of primary resting CD4+ T cells
      through TLR2 activation.
AB  - Sexually transmitted infections increase the likelihood of HIV-1 transmission. We
      investigated the effect of Neisseria gonorrheae (gonococcus [GC]) exposure on HIV
      replication in primary resting CD4(+) T cells, a major HIV target cell during the
      early stage of sexual transmission of HIV. GC and TLR2 agonists, such as
      peptidylglycan (PGN), Pam(3)CSK(4), and Pam(3)C-Lip, a GC-derived synthetic
      lipopeptide, but not TLR4 agonists including LPS or GC lipooligosaccharide
      enhanced HIV-1 infection of primary resting CD4(+) T cells after viral entry.
      Pretreatment of CD4(+) cells with PGN also promoted HIV infection. Anti-TLR2 Abs
      abolished the HIV enhancing effect of GC and Pam(3)C-Lip, indicating that GC
      mediated enhancement of HIV infection of resting CD4(+) T cells was through TLR2.
      IL-2 was required for TLR2-mediated HIV enhancement. PGN and GC induced cell
      surface expression of T cell activation markers and HIV coreceptors, CCR5 and
      CXCR4. The maximal postentry HIV enhancing effect was achieved when PGN was added
      immediately after viral exposure. Kinetic studies and analysis of HIV DNA
      products indicated that GC exposure and TLR2 activation enhanced HIV infection at
      the step of nuclear import. We conclude that GC enhanced HIV infection of primary
      resting CD4(+) T cells through TLR2 activation, which both increased the
      susceptibility of primary CD4(+) T cells to HIV infection as well as enhanced HIV
      infected CD4(+) T cells at the early stage of HIV life cycle after entry. This
      study provides a molecular mechanism by which nonulcerative sexually transmitted
      infections mediate enhancement of HIV infection and has implication for HIV
      prevention and therapeutics.

PMID- 20147632
TI  - Adenosine deaminase modulation of telomerase activity and replicative senescence
      in human CD8 T lymphocytes.
AB  - Increased proportions of CD8 T lymphocytes lacking expression of the CD28
      costimulatory receptor have been documented during both aging and chronic
      infection with HIV-1, and their abundance correlates with numerous deleterious
      clinical outcomes. CD28-negative cells also arise in cell cultures of
      CD8(+)CD28(+) following multiple rounds of Ag-driven proliferation, reaching the
      end stage of replicative senescence. The present study investigates the role of a
      second T cell costimulatory receptor component, adenosine deaminase (ADA), on the
      process of replicative senescence. We had previously reported that CD28 signaling
      is required for optimal telomerase upregulation. In this study, we show that the
      CD8(+)CD28(+) T lymphocytes that are ADA(+) have significantly greater telomerase
      activity than those that do not express ADA and that ADA is progressively lost as
      cultures progress to senescence. Because ADA converts adenosine to inosine, cells
      lacking this enzyme might be subject to prolonged exposure to adenosine, which
      has immunosuppressive effects. Indeed, we show that chronic exposure of CD8 T
      lymphocytes to exogenous adenosine accelerates the process of replicative
      senescence, causing a reduction in overall proliferative potential, reduced
      telomerase activity, and blunted IL-2 gene transcription. The loss of CD28
      expression was accelerated, in part due to adenosine-induced increases in
      constitutive caspase-3, known to act on the CD28 promoter. These findings provide
      the first evidence for a role of ADA in modulating the process of replicative
      senescence and suggest that strategies to enhance this enzyme may lead to novel
      therapeutic approaches for pathologies associated with increases in senescent CD8
      T lymphocytes.

PMID- 20147634
TI  - The endoplasmic reticulum stress-inducible protein, Herp, is a potential
      triggering antigen for anti-DNA response.
AB  - Anti-dsDNA Abs are highly specific indicators of systemic lupus erythematosus
      (SLE) and play a pathogenic role in lupus nephritis. Human anti-dsDNA Abs are
      most likely generated by an Ag-driven mechanism. However, the Ag responsible for
      triggering anti-dsDNA Ab production has not been identified. To search for
      proteins that are cross-reactive with anti-dsDNA Abs, we screened a cDNA library
      from a patient with SLE with single-chain Fv of O-81 human anti-ss/dsDNA mAb by
      using a two-hybrid system. Homocysteine-induced ER protein (Herp), an endoplasmic
      reticulum (ER) stress-inducible ER membrane protein, was identified and shown to
      bind to original O-81 Ab and human lupus anti-dsDNA Abs. Some IgG purified from
      patients with active SLE by Herp-immobilized affinity chromatography bound to
      dsDNA. BALB/c mice immunized with Herp showed IgG anti-dsDNA Abs, IgG anti
      nucleosome Abs, and glomerular IgG deposition. Herp reactivity was strongly
      positive in a proportion of PBLs from patients with active SLE, but undetectable
      in those from healthy controls. Moreover, activation of caspases was observed in
      the Herp-positive cells, implying that ER stress-induced apoptosis likely occurs
      in patients with active SLE. Herp is exposed on blebs of ER stress-induced
      apoptotic cells, suggesting that Herp can be recognized by immune cells. These
      results indicate that Herp mimics structural determinants of DNA immunologically
      and can be immunogenic in vivo. Thus, Herp represents a candidate autoantigen for
      anti-DNA Abs. This study may help explain how common environmental factors induce
      the production of anti-DNA Abs and contribute the development of SLE.

PMID- 20147633
TI  - IL-4 regulates skin homeostasis and the predisposition toward allergic skin
      inflammation.
AB  - IL-4 promotes the development of Th2 cells and allergic inflammation. In atopic
      dermatitis lesions, IL-4 decreases the expression of multiple genes associated
      with innate defense, including genes in the epidermal differentiation complex
      (EDC) that regulate epidermal barrier function. However, it is not clear whether
      IL-4 also contributes to homeostatic control of EDC genes. In this report, we
      demonstrate that expression of EDC genes and barrier function is increased in the
      absence of endogenous IL-4. Mice that express a constitutively active Stat6
      (Stat6VT) are prone to the development of allergic skin inflammation and have
      decreased expression of EDC genes. IL-4 deficiency protects Stat6VT transgenic
      mice from the development of allergic skin inflammation and decreased recovery
      time in barrier function following skin irritation, with a concomitant increase
      in EDC gene expression. These data suggest that IL-4 plays an important role in
      regulating epidermal homeostasis and innate barrier function.

PMID- 20147635
TI  - Nitric oxide is involved in Mycobacterium bovis bacillus Calmette-Guerin
      activated Jagged1 and Notch1 signaling.
AB  - Pathogenic mycobacteria have evolved unique strategies to survive within the
      hostile environment of macrophages. Modulation of key signaling cascades by NO,
      generated by the host during infection, assumes critical importance in overall
      cell-fate decisions. We show that NO is a critical factor in Mycobacterium bovis
      bacillus Calmette-Guerin-mediated Notch1 activation, as the generation of
      activated Notch1 or expression of Notch1 target genes matrix metalloproteinase-9
      (MMP-9) or Hes1 was abrogated in macrophages derived from inducible NO synthase
      (iNOS) knockout (iNOS(-/-)), but not from wild-type, mice. Interestingly,
      expression of the Notch1 ligand Jagged1 was compromised in M. bovis bacillus
      Calmette-Guerin-stimulated iNOS(-/-) macrophages, and loss of Jagged1 expression
      or Notch1 signaling could be rescued by NO donors. Signaling perturbations or
      genetic approaches implicated that robust expression of MMP-9 or Hes1 required
      synergy and cross talk between TLR2 and canonical Notch1-PI3K cascade. Further,
      CSL/RBP-Jk contributed to TLR2-mediated expression of MMP-9 or Hes1. Correlative
      evidence shows that, in a murine model for CNS tuberculosis, this mechanism
      operates in vivo only in brains derived from WT but not from iNOS(-/-) mice.
      Importantly, we demonstrate the activation of Notch1 signaling in vivo in
      granulomatous lesions in the brains of Mycobacterium tuberculosis-infected human
      patients with tuberculous meningitis. Current investigation identifies NO as a
      pathological link that modulates direct cooperation of TLR2 with Notch1-PI3K
      signaling or Jagged1 to regulate specific components of TLR2 responses. These
      findings provide new insights into mechanisms by which Notch1, TLR2, and NO
      signals are integrated in a cross talk that modulates a defined set of effector
      functions in macrophages.

PMID- 20147636
TI  - Genetic variability of respiratory syncytial viruses (RSV) prevalent in
      Southwestern China from 2006 to 2009: emergence of subgroup B and A RSV as
      dominant strains.
AB  - Respiratory syncytial virus (RSV) is the most commonly identified viral agent in
      young children with acute respiratory tract infections (ARIs) and often causes
      repeated infections throughout life. This study investigated the genetic
      variability of the attachment (G) protein gene among RSV strains prevalent in
      southwestern China. Reverse transcription-PCR (RT-PCR) for a fragment of the RSV
      G gene was performed with nasopharyngeal aspirates (NPAs) collected from children
      with ARIs hospitalized in Chongqing Children's Hospital, Chongqing, China. A
      total of 1,387 NPA specimens were collected from April 2006 to March 2009, and
      439 (31.7%) were positive for RSV. During the study period, subgroup A and B
      viruses accounted for 79.5% (349/439) and 19.8% (87/439) of the total positive
      samples, respectively. Both subgroup A and B viruses were identified in three
      samples. Subgroup A viruses were predominant during two epidemic seasons (2006 to
      2008), while subgroup B strains prevailed during the 2008-2009 epidemic season.
      Phylogenetic analyses showed that all 30 group A strains could be clustered into
      one genotype, genotype GA2, and 30 group B strains could be clustered into three
      genotypes, genotypes GB1, GB3, and BA, among which 17 genotype BA strains were
      detected from 23 group B strains selected during the 2008-2009 epidemic season.
      The G gene of genotype BA was predicted to encode proteins of five different
      lengths. These data suggest that group A RSV likely predominated in southwestern
      China and that a new genotype of subgroup B with a 60-nucleotide insertion, named
      BA-like virus, became the dominant genotype in the 2008-2009 epidemic season.

PMID- 20147637
TI  - Aspergillus PCR: one step closer to standardization.
AB  - PCR has been used as an aid in the diagnosis of invasive aspergillosis for almost
      2 decades. A lack of standardization has limited both its acceptance as a
      diagnostic tool and multicenter clinical evaluations, preventing its inclusion in
      disease-defining criteria. In 2006, the European Aspergillus PCR Initiative was
      formed. The aim of the initiative was to provide optimal standardized protocols
      for the widespread clinical evaluation of the Aspergillus PCR to determine its
      diagnostic role and allow inclusion in disease diagnosis criteria. Quality
      control panels were developed and circulated to centers for evaluation of the
      existing methodology before recommendations based on the initial results were
      proposed for further panels. The centers were anonymously classified as
      "compliant" or "noncompliant," according to whether they had followed the
      proposed recommendations before the performance parameters were determined and
      meta-regression analysis was performed. Most PCR amplification systems provided
      similar detection thresholds, although positivity was a function of the fungal
      burden. When PCR amplification was combined with DNA extraction, 50% of the
      centers failed to achieve the same level of detection. Meta-regression analysis
      showed positive correlations between sensitivity and extraction protocols
      incorporating the proposed recommendations and the use of bead beating, white
      cell lysis buffer, and an internal control PCR. The use of elution volumes above
      100 microl showed a negative correlation with sensitivity. The efficiency of the
      Aspergillus PCR is limited by the extraction procedure and not by PCR
      amplification. For PCR testing of whole blood, it is essential that large blood
      volumes (>or=3 ml) be efficiently lysed before bead beating to disrupt the fungal
      cell and performance of an internal control PCR to exclude false negativity. DNA
      should be eluted in volumes of <100 microl.

PMID- 20147638
TI  - Etiological spectrum of clinically diagnosed Japanese encephalitis cases reported
      in Guizhou Province, China, in 2006.
AB  - The proportion of laboratory-confirmed Japanese encephalitis (JE) virus (JEV)
      infections was compared to the number of JE cases reported on the basis of
      seasonality and the clinical symptoms of hospitalized patients in Guizhou
      Province, China, between April and November 2006. Of the 1,837 patients with
      reported JE, 1,382 patients in nine prefectures were investigated. JE was
      confirmed in 1,210 of 1,382 (87.6%) patients by a JEV-specific immunoglobulin M
      (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA), heminested
      reverse transcriptase PCR, and virus isolation. Two strains of JEV belonging to
      genotype 1 were isolated. Other viral pathogens responsible for encephalitis,
      including echovirus, mumps virus, herpes simplex virus, and cytomegalovirus, were
      identified in 67 of 172 (38.9%) JE-negative cases. On the basis of the
      distribution of the laboratory-confirmed JE cases from different hospitals
      according to the Chinese administrative division, which included hospitals at the
      provincial, city, county, and township levels, county hospitals detected the
      highest number of JE cases (81.8%), whereas township hospitals detected the
      smallest number of JE cases (1.4%). Provincial and city hospitals had the highest
      and lowest rates of accuracy of providing a clinical diagnosis of JE, as
      confirmed by laboratory testing (91.8% and 76.7%, respectively). This study
      demonstrates that laboratory confirmation improves the accuracy of diagnosis of
      JE and that an enhanced laboratory capacity is critical for JE surveillance as
      well as the identification of other pathogens that cause encephalitic syndromes
      with clinical symptoms similar to those caused by JEV infection.

PMID- 20147639
TI  - Distribution of melioidosis cases and viable Burkholderia pseudomallei in soil:
      evidence for emerging melioidosis in Taiwan.
AB  - A survey for the prevalence if Burkholderia pseudomallei in soil in Taiwan found
      that its incidence is comparable to that in other regions of the world where
      melioidosis is endemic. The presence of identical genetic patterns among the
      clinical and environmental isolates evaluated suggested a link between the
      pathogens present in contaminated soil and the emergence of indigenous
      melioidosis.

PMID- 20147641
TI  - Globicatella sanguinis meningitis associated with human carriage.
AB  - Globicatella sanguinis is a rare cause of acute meningitis. We demonstrated human
      carriage of Globicatella by identifying cefotaxime-resistant strains in groin and
      rectal specimens 9 months after invasive infection. The pathogenic strain
      isolated from the cerebrospinal fluid and the carriage strains were accurately
      identified by sodA gene sequence analysis.

PMID- 20147640
TI  - Outbreak of acute respiratory infection among infants in Lisbon, Portugal, caused
      by human adenovirus serotype 3 and a new 7/3 recombinant strain.
AB  - Human adenoviruses (AdVs) typically cause mild illnesses in otherwise healthy
      hosts. We investigated a pediatric outbreak of acute respiratory infection with
      fatal outcomes that occurred in Lisbon, Portugal, in 2004. Biological specimens
      were collected from 83 children attending two nurseries, a kinesiotherapy clinic,
      and the household of a nanny. Adenovirus infection was confirmed in 48 children
      by PCR and virus isolation. Most (96%) isolates were classified as being of
      subspecies B1. Phylogenetic analysis of fiber and hexon gene sequences revealed
      that most infants were infected with AdV serotype 3 (AdV3) strains. Infants
      attending one nursery harbored a new recombinant strain containing an AdV
      serotype 7 hexon and serotype 3 fiber (AdV7/3). Both the AdV3 and the AdV7/3
      strains caused fatal infections. Two different serotype 3 strains were
      circulating in Lisbon in 2004, and the new AdV7/3 recombinant type originated
      from only one of those strains. These results demonstrate that recombination
      leads to the emergence of new adenovirus strains with epidemic and lethal
      potential.

PMID- 20147642
TI  - Multicenter external quality assessment of molecular methods for detection of
      human herpesvirus 6.
AB  - The purpose of this study was to evaluate the performance of laboratories for the
      detection and quantification of human herpesvirus 6 (HHV-6) by an external
      quality assessment (EQA) evaluation. The HHV-6 EQA panel consisted of eight
      samples containing various concentrations of HHV-6 type A (strain GS) or type B
      (strain Z29), two samples containing other herpesviruses (i.e., human
      cytomegalovirus [HCMV] and Epstein-Barr virus [EBV]), and two HHV-6-negative
      samples. Panel samples were prepared in human plasma, heat inactivated, and
      lyophilized. Panel distribution, data management, and analysis were coordinated
      by Quality Control for Molecular Diagnostics (QCMD), Glasgow, United Kingdom.
      Fifty-one laboratories participated and submitted 57 data sets. Eleven (19.3%)
      data sets were generated using conventional in-house assays, 11 (19.3%) data sets
      using commercial real-time PCR assays, and 35 (61.4%) data sets using in-house
      real-time PCR assays. The presence of HHV-6 DNA at viral loads exceeding 6,000
      copies/ml was detected by all participants, and over 80% of the participants
      still reported correct qualitative results for the sample containing just over
      200 copies/ml. The false-positivity rate was 1.8% for both the negative samples
      and the samples containing HCMV or EBV DNA. The majority (23/33; 69.7%) of
      quantitative data sets were generated using in-house real-time PCR assays. The
      standard deviations of the geometric means of the samples ranged from 0.5 to 0.7
      log(10). The results of this first international EQA demonstrate encouraging
      analytical sensitivity for the detection of HHV-6-DNA in human plasma, although
      we observed extensive interlaboratory variation of quantitative HHV-6 DNA
      results. Standardization needs to be improved to allow further elucidation of the
      clinical significance of HHV-6 loads.

PMID- 20147643
TI  - Comparison of bacterial antigen test and gram stain for detecting classic
      meningitis bacteria in cerebrospinal fluid.

PMID- 20147644
TI  - Two unusual cases of severe soft tissue infection caused by Streptococcus
      dysgalactiae subsp. equisimilis.
AB  - We present two cases of invasive infection caused by Streptococcus dysgalactiae
      subsp. equisimilis, one that showed rapidly developing necrotizing fasciitis in a
      previously healthy man and one that showed severe cellulitis and septic shock
      even though the bacterium possessed a mutated emm gene, predicted to encode a
      truncated M protein.

PMID- 20147645
TI  - Public hospital-based laboratory experience during an outbreak of pandemic
      influenza A (H1N1) virus infections.
AB  - The experience of a public hospital virology laboratory during a springtime 2009
      outbreak of a novel influenza A (H1N1) virus in New York State is described.
      Influenza virus was isolated from 145 of 613 respiratory swab specimens. Symptoms
      of fever (temperature, 102.7 +/- 0.32 degrees F), cough, upper respiratory
      infection, myalgia, and headache were reported. Atypical symptoms of
      nausea/vomiting and diarrhea were also observed. Illness occurred mainly in
      patients <or=21 years of age (85/145 patients). Only two patients were >or=65
      years old. Compared to the results of traditional culture methods, the
      sensitivities of a rapid chromatographic influenza A and B virus immunoassay and
      rapid shell vial culture were 70.3% and 98.6%, respectively. A sensitivity of 80%
      was obtained by testing 50 specimens by a direct fluorescent-antibody (DFA)
      assay. The observation of adequate numbers of cells on the DFA assay slides
      suggests that the low sensitivity of the chromatographic immunoassay may result
      from its intrinsic nature and not from improper specimen collection. A reverse
      transcription-PCR (RT-PCR) assay of 45 specimens performed off-site yielded 21
      novel (H1N1) viruses and 2 seasonal (H3N2) influenza viruses. The mean time
      interval of 5.69 +/- 0.37 days from specimen collection to the availability of RT
      PCR results limited the value of this assay for patient care. In laboratories
      lacking on-site molecular capabilities, shell vial techniques can rapidly (about
      1 day) confirm negative results and/or identify false-negative chromatographic
      immunoassay results. Laboratories lacking culture capabilities may also use the
      DFA assay to confirm or replace the results obtained by these immunoassays.
      Increasing testing demands caused shortages in commodities and personnel.
      Alternative testing strategies and planning are necessary in order to optimize
      virus detection and ensure appropriate resource allocation.

PMID- 20147646
TI  - Prognostic features of galactomannan antigenemia in galactomannan-positive
      invasive aspergillosis.
AB  - Prognostic features of serum galactomannan (GM) remain poorly defined in patients
      with GM-positive invasive aspergillosis (GPA). We identified 93 patients with
      proven or probable invasive aspergillosis (IA) and GM values of >or=0.50 from
      January 2005 to March 2009. We used Cox modeling of time to 6- and 12-week
      mortality for the GM level at the time of diagnosis (GM(0)), GM decay in the week
      following diagnosis in 72 patients with >or=2 GM values, other predictors of
      mortality, and antifungal use during the week following diagnosis. Six-week
      mortality was 55% in the whole cohort and 43% in patients with >or=2 GM
      determinations. The hazard ratio (HR) of GM(0) per unit increase and 1-week GM
      decay per unit decline per week were 1.25 (95% confidence interval [CI], 1.01 to
      1.54; P = 0.04) and 0.78 (95% CI, 0.63 to 0.96; P = 0.02), respectively,
      adjusting for other predictors of IA mortality; these values remained stable
      after adjusting for antifungal use and were predictive of all-cause mortality at
      12 weeks with similar adjusted HR values. We conclude that the combination of
      GM(0) and 1-week GM decay is predictive of all-cause mortality in patients with
      GPA, independent of other traditional risk factors for mortality and antifungal
      exposure, supporting GM decay as a potential surrogate endpoint for future
      antifungal therapeutic trials.

PMID- 20147647
TI  - Serotype and genotype replacement among macrolide-resistant invasive Pneumococci
      in adults: mechanisms of resistance and association with different transposons.
AB  - The aim of this study was to analyze trends in adult invasive pneumococcal
      disease (IPD) due to macrolide-resistant strains and to study the evolution of
      serotypes, genotypes, and macrolide-resistant determinants of strains collected
      in a prospective study between 1999 and 2007 in Barcelona, Spain. IPD due to
      macrolide-resistant strains of serotypes included in the 7-valent conjugate
      vaccine (PCV7) decreased from 2.16/100,000 (pre-PCV7 period, 1999 to 2001) to
      0.80/100,000 (late-PCV7 period, 2005 to 2007) (P = 0.001), whereas IPD due to
      macrolide-resistant strains of non-PCV7 serotypes increased from 1.08/100,000 to
      2.83/100,000 (P < 0.001). These changes were related to a fall of clones of PCV7
      serotypes (ST81 [P < 0.05], ST90, ST315, and ST17) and an increase in new clones
      of serotypes 19A and 24F (ST230) and 33F (ST717) in the late-PCV7 period. The
      most common phenotype was MLS(B) (90.9%), related to the erm(B) gene. The
      frequent association between MLS(B) phenotype and tetracycline resistance [tet(M)
      gene], was related to transposons of the Tn916-family such as Tn6002 or Tn3872.
      In conclusion, overall adult IPD rates due to macrolide-resistant pneumococci
      stabilized between 1999 and 2007 in Barcelona. The decrease in macrolide
      resistant PCV7 pneumococci was balanced by the increase in macrolide-resistant
      non-PCV7 pneumococci.

PMID- 20147648
TI  - Novel hot spot of IS6110 insertion in Mycobacterium tuberculosis.
AB  - We describe a hot spot for the insertion of IS6110 in Mycobacterium tuberculosis
      located in the area of region of difference 724 (RD724). Because RD724 defines
      sublineage 724 of M. tuberculosis, caution must be exercised when screening for
      RD724, as different polymorphisms can be observed in this region.

PMID- 20147649
TI  - Cost-effective modification of a commercial PCR assay for detection of
      methicillin-resistant or -susceptible Staphylococcus aureus in positive blood
      cultures.
AB  - Real-time detection of methicillin-resistant Staphylococcus aureus (MRSA) and
      methicillin-susceptible S. aureus (MSSA) in cases of clinical bacteremia may
      promote appropriate antimicrobial therapy and infection control. Expense inherent
      to molecular diagnostics may prevent laboratories from utilizing real-time PCR
      for this purpose. BD GeneOhm StaphSR assay master mix was reconstituted and
      aliquoted into SmartCycler tubes in 25-mul volumes (freshly reconstituted master
      mix), with a portion being frozen at -70 degrees C (frozen master mix).
      Incubation of 40 previously analyzed lysates from positive BacT/Alert SA and SN
      blood culture bottles (identified as 10 MRSA strains, 10 MSSA strains, 12
      coagulase-negative Staphylococcus strains, and 8 Micrococcus strains) in freshly
      reconstituted master mix and master mix frozen between 1 week and 6 months
      generated the expected results in all PCRs. Similarly, positive- and negative
      control reagents stored frozen at -70 degrees C for up to 18 weeks yielded the
      expected reactions. Prospective analysis of 244 positive blood culture samples
      utilizing 1-week-frozen master mix and freshly reconstituted master mix yielded a
      1.2% discordant rate upon initial testing due to three unresolved results (two
      unresolved results for freshly reconstituted master mix and one unresolved result
      for frozen master mix). Repeat testing produced a final 100% concordance rate
      between the two master mix preparations. Use of master mix that was frozen up to
      6 months did not compromise performance of the BD GeneOhm StaphSR assay. This
      modification, resulting in less reagent waste, may allow a greater number of
      laboratories to consider real-time PCR methodology for detection of bacteremia
      caused by MRSA and MSSA.

PMID- 20147650
TI  - Care management service and falls prevention: a case-control study in a Chinese
      population.
AB  - OBJECTIVE: This study evaluates the effect of a care management service (CMS) on
      falls in older adults. METHOD: This is a retrospective case-control study with 78
      CMS recipients as the case group who received CMS and another 312 community
      dwelling frail elders as the control group.The groups were matched by age,
      gender, activity of daily living, cognitive impairment, and unsteady gait. Thus
      they were comparable in characteristics and frailty. RESULTS: Among the 390
      participants, 89 older adults (23.0%) had falls in the 90 days prior to the
      survey. After controlling for the identified risk factors for falls, the odds
      ratio of CMS was 0.27 (95% confidence interval = 0.110-0.663, p < .01).
      DISCUSSION: These findings indicate that CMS recipients have a lower chance for
      falls compared to their counterparts. The two features of CMS (comprehensive
      assessment and multidisciplinary actions to reduce fall risks) are discussed.

PMID- 20147651
TI  - Prevalence and correlates of functional status in an older community-
      representative sample in Brazil.
AB  - OBJECTIVE: Information on dependency level of elderly in rapidly aging developing
      countries is limited, but this is needed to ascertain the extent of need for help
      with activities of daily living (ADLs). METHOD: In-person information was
      obtained in 1995 from a statewide survey of representative community residents
      >/=60 years of age in the state of Rio Grande do Sul, Brazil (N = 7,040), on
      demographic characteristics, health conditions, social ties, health behaviors,
      and ADL performance. RESULTS: Nearly 40% needed help with one or more ADLs. In
      controlled analyses, need for help approximately doubled with each succeeding
      decade. Increased education and income and regular physical activity reduced
      risk. Selected health conditions (stroke, depression, poor self-rated health)
      were consistently associated with need for help. DISCUSSION: A large proportion
      of noninstitutionalized elderly have ADL problems. In addition to health care,
      interventions promoting equity of access to education and economic opportunity
      could reduce ADL dependency in coming generations.

PMID- 20147652
TI  - T-type current modulation by the actin-binding protein Kelch-like 1.
AB  - We report a novel form of modulation of T-type calcium currents carried out by
      the neuronal actin-binding protein (ABP) Kelch-like 1 (KLHL1). KLHL1 is a
      constitutive neuronal ABP localized to the soma and dendritic arbors; its genetic
      elimination in Purkinje neurons leads to dendritic atrophy and motor
      insufficiency. KLHL1 participates in neurite outgrowth and upregulates voltage
      gated P/Q-type calcium channel function; here we investigated KLHL1's role as a
      modulator of low-voltage-gated calcium channels and determined the molecular
      mechanism of this modulation with electrophysiology and biochemistry.
      Coexpression of KLHL1 with Ca(V)3.1 or Ca(V)3.2 (alpha(1G) or alpha(1H) subunits)
      caused increases in T-type current density (35%) and calcium influx (75-83%) when
      carried out by alpha(1H) but not by alpha(1G). The association between KLHL1 and
      alpha(1H) was determined by immunoprecipitation and immunolocalization in brain
      membrane fractions and in vitro in HEK-293 cells. Noise analysis showed that
      neither alpha(1H) single-channel conductance nor open probability was altered by
      KLHL1, yet a significant increase in channel number was detected and further
      corroborated by Western blot analysis. KLHL1 also induced an increase in
      alpha(1H) current deactivation time (tau(deactivation)). Interestingly, the
      majority of KLHL1's effects were eliminated when the actin-binding motif (kelch)
      was removed, with the exception of the calcium influx increase during action
      potentials, indicating that KLHL1 interacts with alpha(1H) and actin and
      selectively regulates alpha(1H) function by increasing the number of alpha(1H)
      channels. This constitutes a novel regulatory mechanism of T-type calcium
      currents and supports the role of KLHL1 in the modulation of cellular
      excitability.

PMID- 20147653
TI  - Odors activate dual pathways, a TRPC2 and a AA-dependent pathway, in mouse
      vomeronasal neurons.
AB  - Located at the anterior portion of the nose, the paired vomeronasal organs (VNO)
      detect odors and pheromones. In vomeronasal sensory neurons (VSNs) odor responses
      are mainly mediated by phospholipase C (PLC), stimulation of which elevates
      diacylglycerol (DAG). DAG activates a transient receptor potential channel
      (TRPC2) leading to cell depolarization. In this study, we used a natural
      stimulus, urine, to elicit odor responses in VSNs and found urine responses
      persisted in TRPC2(-/-) mice, suggesting the existence of a TRPC2-independent
      signal transduction pathway. Using perforated patch-clamp recordings on isolated
      VSNs from wild-type (WT) and TRPC2(-/-) mice, we found a PLC inhibitor blocked
      urine responses from all VSNs. Furthermore, urine responses were reduced by
      blocking DAG lipase, an enzyme that produces arachidonic acid (AA), in WT mice
      and abolished in TRPC2(-/-) mice. Consistently, direct stimulation with AA
      activated an inward current that was independent of TRPC2 channels but required
      bath Ca(2+) and was blocked by Cd(2+). With the use of inside-out patches from
      TRPC2(-/-) VSNs, we show that AA activated a channel that also required Ca(2+).
      Together, these data from WT and TRPC2(-/-) mice suggest that both DAG and its
      metabolite, AA, mediate excitatory odor responses in VSNs, by activating two
      types of channels, a TRPC2 and a separate Ca(2+)-permeable channel.

PMID- 20147654
TI  - Neuronal expression of sodium/bicarbonate cotransporter NBCn1 (SLC4A7) and its
      response to chronic metabolic acidosis.
AB  - The sodium-bicarbonate cotransporter NBCn1 (SLC4A7) is an acid-base transporter
      that normally moves Na(+) and HCO(3)(-) into the cell. This membrane protein is
      sensitive to cellular and systemic pH changes. We examined NBCn1 expression and
      localization in the brain and its response to chronic metabolic acidosis. Two new
      NBCn1 antibodies were generated by immunizing a rabbit and a guinea pig. The
      antibodies stained neurons in a variety of rat brain regions, including
      hippocampal pyramidal neurons, dentate gyrus granular neurons, posterior cortical
      neurons, and cerebellar Purkinje neurons. Choroid plexus epithelia were also
      stained. Double immunofluorescence labeling showed that NBCn1 and the
      postsynaptic density protein PSD-95 were found in the same hippocampal CA3
      neurons and partially colocalized in dendrites. PSD-95 was pulled down from rat
      brain lysates with the GST/NBCn1 fusion protein and was also coimmunoprecipitated
      with NBCn1. Chronic metabolic acidosis was induced by feeding rats with normal
      chow or 0.4 M HCl-containing chow for 7 days. Real-time PCR and immunoblot showed
      upregulation of NBCn1 mRNA and protein in the hippocampus of acidotic rats. NBCn1
      immunostaining was enhanced in CA3 neurons, posterior cortical neurons, and
      cerebellar granular cells. Intraperitoneal administration of N-methyl-d-aspartate
      caused neuronal death determined by caspase-3 activity, and this effect was more
      severe in acidotic rats. Administering N-methyl-d-aspartate also inhibited NBCn1
      upregulation in acidotic rats. We conclude that NBCn1 in neurons is upregulated
      by chronic acid loads, and this upregulation is associated with glutamate
      excitotoxicity.

PMID- 20147655
TI  - Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured
      by [11C]PiB.
AB  - OBJECTIVE: To investigate whether longitudinal declines in cognition are
      associated with higher fibrillar amyloid-beta (Abeta) deposition in vivo in
      individuals without dementia. METHOD: [(11)C]PiB images were obtained to measure
      fibrillar Abeta burden in 57 participants without dementia from the Baltimore
      Longitudinal Study of Aging. Participants (33 men, 24 women) had a mean (SD) age
      of 78.7 (6.2) years. Six participants (4 men, 2 women) had mild cognitive
      impairment defined as Clinical Dementia Rating = 0.5. To measure [(11)C]PiB
      retention, distribution volume ratios (DVR) for 15 regions of interest were
      estimated by fitting a simplified reference tissue model to the measured time
      activity curves. Mixed effects regression was used to predict cognitive
      trajectories over time using data before and including time of PiB (mean follow
      up 10.8 years), with mean cortical DVR, age at baseline, sex, and education as
      independent predictors. Voxel-based analysis identified local associations.
      RESULTS: [(11)C]PiB retention was higher in older individuals. Greater declines
      over time in mental status and verbal learning and memory, but not visual memory,
      were associated significantly with higher PiB retention. Voxel-based analysis
      showed significant associations in frontal and lateral temporal regions.
      CONCLUSIONS: Higher Abeta deposition is associated with greater longitudinal
      decline in mental status and verbal memory in the preceding years. The
      differential association for verbal but not visual memory may reflect the greater
      reliance of verbal word list learning on prefrontal regions, which show early
      Abeta deposition. Prospective imaging may help distinguish between individuals
      with evolving neuropathology who develop accelerated cognitive decline vs those
      with normal aging.

PMID- 20147656
TI  - Gray matter perfusion correlates with disease severity in ALS.
AB  - OBJECTIVE: The goal of this study is to determine if regional brain perfusion, as
      measured by arterial spin labeling (ASL) MRI, is correlated with clinical
      measures of amyotrophic lateral sclerosis (ALS) disease severity. The presence of
      such a relationship would indicate a possible role for ASL perfusion as a marker
      of disease severity and upper motor neuron involvement in ALS. METHODS: Disease
      severity was assessed in 16 subjects with ALS (age 54 +/- 11) using the
      Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and the pulmonary
      function measure, forced vital capacity (FVC). Upper motor neuron involvement was
      assessed by testing rapid tapping of the fingers and feet. Magnetic resonance
      perfusion images were coregistered with structural T1-weighted MRI, corrected for
      partial volume effects using the structural images and normalized to a study
      specific atlas. Correlations between perfusion and ALS disease severity were
      analyzed, using statistical parametric mapping, and including age as a factor.
      Analyses were adjusted for multiple clusters. RESULT: ALS severity, as measured
      by the ALSFRS and FVC, was correlated with gray matter perfusion. This
      correlation was predominantly observed in the hemisphere contralateral to the
      more affected limbs. ALSFRS scores correlated with perfusion in the contralateral
      frontal and parietal lobe (p < 0.001) and ipsilateral frontal lobe (p < 0.02).
      FVC scores correlated with gray matter perfusion in contralateral frontal lobe (p
      < 0.001). Upper motor neuron involvement, as measured by rapid finger tapping,
      correlated bilaterally with perfusion in the middle cingulate gyrus (p < 0.001).
      CONCLUSION: Amyotrophic lateral sclerosis (ALS) severity is correlated with brain
      perfusion as measured by arterial spin labeling (ASL) perfusion. This correlation
      appears to be independent of brain atrophy. ASL perfusion may be a useful tool
      for monitoring disease progression and assessing treatment effects in ALS.

PMID- 20147657
TI  - Is migraine a dangerous disease?

PMID- 20147659
TI  - The science of eliminating health disparities: embracing a new paradigm.

PMID- 20147658
TI  - Migraine and cardiovascular disease: a population-based study.
AB  - OBJECTIVES: Although the relationship between migraine and cardiovascular disease
      (CVD) has been studied, several questions remain unanswered. Herein we contrast
      the rate of diagnosed CVD as well as of risk factors for CVD in individuals with
      migraine with and without aura (MA and MO) and in controls. METHODS: In this case
      control study, migraineurs (n = 6,102) and controls (n = 5,243) were
      representative of the adult US population. Headache diagnosis was formally
      assigned using a validated mailed questionnaire which also obtained details on
      treatment, comorbidities, and other variables. CVD events were obtained based on
      self-reported medical diagnosis. Risk factors for CVD and modified Framingham
      scores were computed. RESULTS: In unadjusted analyses, migraine overall and MA
      were associated with myocardial infarction, stroke, and claudication, and MO was
      associated with myocardial infarction and claudication. Migraineurs were more
      likely than controls to have a medical diagnosis of diabetes (12.6% vs 9.4%, odds
      ratio [OR] 1.4, 95% confidence interval [CI] 1.2-1.6), hypertension (33.1% vs
      27.5%, OR 1.4, 95% CI 1.3-1.6), and high cholesterol (32.7% vs 25.6%, OR 1.4, 95%
      CI 1.3-1.5). Risk was highest in MA, but remained elevated in MO. Framingham
      scores were significantly higher in MO and MA than in controls. After adjustments
      (gender, age, disability, treatment, CVD risk factors), migraine remained
      significantly associated with myocardial infarction (OR 2.2, 95% CI 1.7-2.8),
      stroke (OR 1.5, 95% CI 1.2-2.1), and claudication (OR 2.69, 95% CI 1.98-3.23).
      CONCLUSION: Both migraine with and without aura are associated with
      cardiovascular disease (CVD) and with risk factors for CVD. However, since our
      sample size is large, the clinical relevance of the differences is yet to be
      established.

PMID- 20147660
TI  - The science of eliminating health disparities: summary and analysis of the NIH
      summit recommendations.
AB  - In December 2008, the National Institutes of Health (NIH) sponsored the first NIH
      Summit showcasing its investment and contribution to health disparities research
      and unveiling a framework for moving this important field forward. The Summit,
      titled "The Science of Eliminating Health Disparities," drew on extensive
      experience of experts leading health disparities research transformation in
      diverse fields. The Summit also provided a historic educational opportunity to
      contribute to health care reform. The theme, addressing disparities through
      integration of science, practice, and policy, introduced a paradigm for advancing
      research through transformational, translational, and transdisciplinary research.
      Engaging active participation throughout the Summit generated recommendations
      bridging science, practice, and policy, including action on social determinants
      of health, community engagement, broad partnerships, capacity-building, and media
      outreach.

PMID- 20147661
TI  - Health equity and public health leadership.

PMID- 20147662
TI  - Moving toward paradigm-shifting research in health disparities through
      translational, transformational, and transdisciplinary approaches.
AB  - Translational, transdisciplinary, and transformational research stands to become
      a paradigm-shifting mantra for research in health disparities. A windfall of
      research discoveries using these 3 approaches has increased our understanding of
      the health disparities in racial, ethnic, and low socioeconomic status groups.
      These distinct but related research spheres possess unique environments, which,
      when integrated, can lead to innovation in health disparities science. In this
      article, we review these approaches and propose integrating them to advance
      health disparities research through a change in philosophical position and an
      increased emphasis on community engagement. We argue that a balanced combination
      of these research approaches is needed to inform evidence-based practice, social
      action, and effective policy change to improve health in disparity communities.

PMID- 20147663
TI  - Community-based participatory research contributions to intervention research:
      the intersection of science and practice to improve health equity.
AB  - Community-based participatory research (CBPR) has emerged in the last decades as
      a transformative research paradigm that bridges the gap between science and
      practice through community engagement and social action to increase health
      equity. CBPR expands the potential for the translational sciences to develop,
      implement, and disseminate effective interventions across diverse communities
      through strategies to redress power imbalances; facilitate mutual benefit among
      community and academic partners; and promote reciprocal knowledge translation,
      incorporating community theories into the research. We identify the barriers and
      challenges within the intervention and implementation sciences, discuss how CBPR
      can address these challenges, provide an illustrative research example, and
      discuss next steps to advance the translational science of CBPR.

PMID- 20147665
TI  - Overstating social networks' ability to diagnose new cases of HIV.

PMID- 20147666
TI  - Sectoral job training as an intervention to improve health equity.
AB  - A growing literature on the social determinants of health strongly suggests the
      value of examining social policy interventions for their potential links to
      health equity. I investigate how sectoral job training, an intervention favored
      by the Obama administration, might be conceptualized as an intervention to
      improve health equity. Sectoral job training programs ideally train workers, who
      are typically low income, for upwardly mobile job opportunities within specific
      industries. I first explore the relationships between resource redistribution and
      health equity. Next, I discuss how sectoral job training theoretically
      redistributes resources and the ways in which these resources might translate
      into improved health. Finally, I make recommendations for strengthening the link
      between sectoral job training and improved health equity.

PMID- 20147667
TI  - Decline in US breast cancer rates after the Women's Health Initiative:
      socioeconomic and racial/ethnic differentials.
AB  - OBJECTIVES: We investigated whether there were socioeconomic and racial/ethnic
      disparities in recent reported declines in overall US breast cancer incidence
      rates attributed to post-2002 declines in hormone therapy use following
      publication of the Women's Health Initiative study. METHODS: We analyzed 1992
      2005 US breast cancer incidence data from the US Surveillance, Epidemiology and
      End Result (SEER) 13 Registries Database, stratified by race/ethnicity, county
      income level, age, and estrogen receptor (ER) status. RESULTS: As we
      hypothesized, between 1992 and 2005, the temporal pattern of rising and then
      falling US breast cancer incidence rates occurred only among White non-Hispanic
      women who lived in high-income counties, were aged 50 years and older, and had ER
      positive tumors. No such trends were evident--regardless of county income level,
      ER status, or age--among Black non-Hispanic, Asian/Pacific Islander, Hispanic, or
      where numbers were sufficient to conduct meaningful analyses-American
      Indian/Alaska Native women. CONCLUSIONS: The recent decline in US breast cancer
      incidence was not equally beneficial to all women, but instead mirrored the
      social patterning of hormone therapy use. Joint information on socioeconomic
      resources and race/ethnicity is vital for correctly understanding disease
      distribution, including that of breast cancer.

PMID- 20147669
TI  - Disparities in data on Healthy People 2010 physical activity objectives collected
      by accelerometry and self-report.
AB  - OBJECTIVES: We compared findings on physical activity from national accelerometry
      data and Healthy People 2010 self-report data to identify differences in
      disparities by sociodemographic characteristics, gender, age, race/ethnicity,
      education level, and disability status. METHODS: Data were from the 2003 to 2004
      National Health and Nutrition Examination Survey's accelerometry and the Healthy
      People 2010 Midcourse Review. We computed prevalence of inactivity and regular
      moderate- and vigorous-intensity movement according to Healthy People 2010
      operational definitions. RESULTS: Mexican American adults were more active than
      non-Hispanic Blacks and Whites, and groups defined by race/ethnicity and
      educational attainment were more similar in physical activity in accelerometer
      than in self-report data. Disparities by gender and disability status were
      consistent with Healthy People 2010. CONCLUSIONS: Disparities in physical
      activity differ from previous findings. Increased understanding of these
      disparities should be used to design better and more cost-effective physical
      activity interventions. Physical activity surveillance methods should be revised
      to make use of data collection methods that are more valid than self-report.

PMID- 20147668
TI  - The Ohio Cross-Cultural Tobacco Control Alliance: understanding and eliminating
      tobacco-related disparities through the integration of science, practice, and
      policy.
AB  - OBJECTIVES: We examined the development of a process designed to eliminate
      tobacco-related disparities in the state of Ohio and described how a cross
      cultural work group used a multicomponent community planning process to develop
      capacity to address such disparities. METHODS: The community development model
      was used as a guide in the planning process. We employed a case study, focus
      groups, and telephone interviews to assess the process and collect data on
      tobacco use and awareness. We also employed the appreciative inquiry framework to
      create the organizational design for the Ohio Cross-Cultural Tobacco Control
      Alliance (CCTCA), which was formed from the cross-cultural work group and charged
      with addressing tobacco-related disparities in the state. RESULTS: Data on
      tobacco use and awareness were collected from 13 underserved populations. At the
      end of the planning process, the CCTCA was initiated along with structural
      capacity to serve as a new program incubator highlighting tobacco use and
      awareness levels in these populations. CONCLUSIONS: The CCTCA appeared to be an
      effective way to begin mobilizing agencies serving underserved populations by
      providing an operational structure to address tobacco-related disparities. The
      alliance also successfully implemented culturally competent community-based
      programs and policies to help eliminate disparities.

PMID- 20147670
TI  - The Boston Safe Shops model: an integrated approach to community environmental
      and occupational health.
AB  - Small, immigrant-owned businesses, such as auto repair shops and nail salons,
      often face barriers to environmental and occupational health compliance and may
      be a source of neighborhood pollution complaints. The Boston Public Health
      Commission established the Safe Shops Project to improve safety and environmental
      practices in such businesses using a community partnership model that
      incorporates enforcement inspection findings, worker training, technical
      assistance, and referral to health care and business resources. This integrated
      technical assistance approach has led to improved occupational health and
      environmental conditions, adoption of pollution prevention technologies, novel
      problem-solving, and dozens of health screenings and insurance referrals for
      workers and their neighbors.

PMID- 20147672
TI  - Charles V. Roman: physician, writer, educator, historian (1864-1934).

PMID- 20147671
TI  - Racial differences in the association between self-rated health status and
      objective clinical measures among participants in the BARI 2D trial.
AB  - OBJECTIVES: We explored whether and how race shapes perceived health status in
      patients with type 2 diabetes mellitus and coronary artery disease. METHODS: We
      analyzed self-rated health (fair or poor versus good, very good, or excellent)
      and associated clinical risk factors among 866 White and 333 Black participants
      in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.
      RESULTS: Michigan Neuropathy Screening Instrument scores, regular exercise, and
      employment were associated with higher self-rated health (P < .05). Blacks were
      more likely than were Whites to rate their health as fair or poor (adjusted odds
      ratio [OR] = 1.88; 95% confidence interval [CI] = 1.38, 2.57; P < .001). Among
      Whites but not Blacks, a clinical history of myocardial infarction (OR = 1.61;
      95% CI = 1.12, 2.31; P < .001) and insulin use (OR = 1.62; 95% CI = 1.10, 2.38; P
      = .01) was associated with a fair or poor rating. A post-high school education
      was related to poorer self-rated health among Blacks (OR = 1.86; 95% CI = 1.07,
      3.24; P < .001). CONCLUSIONS: Symptomatic clinical factors played a
      proportionally larger role in self-assessment of health among Whites with
      diabetes and coronary artery disease than among Blacks with the same conditions.

PMID- 20147673
TI  - The Journal of the National Medical Association: a voice for civil rights and
      social justice.

PMID- 20147674
TI  - Racial disparities in receipt of influenza and pneumococcus vaccinations among US
      nursing-home residents.
AB  - OBJECTIVES: We examined racial disparities in receipt and documentation of
      influenza and pneumococcus vaccinations among nursing-home residents. METHODS: We
      performed secondary analyses of data from a nationally representative survey of
      White (n = 11 448) and Black (n = 1174) nursing-home residents in 2004. Bivariate
      and multivariate analyses determined racial disparities in receipt of influenza
      vaccination in 2003 and 2004, receipt of pneumococcus vaccination ever, and
      having a documented history for each vaccination. RESULTS: The overall
      vaccination rate was 76.2% for influenza and 48.5% for pneumococcus infection.
      Compared with Whites, Blacks showed a 13% lower vaccination rate and a 5% higher
      undocumentation rate for influenza, and a 15% lower vaccination rate and a 7%
      higher undocumentation rate for pneumococcus. For influenza, the odds ratio (OR)
      for Blacks being unvaccinated was 1.84 (P < or = .001), and the OR for Blacks
      having undocumented vaccination was 1.85 (P = .001). For pneumococcus infection,
      the OR for Blacks being unvaccinated was 1.70 (P < or = .001), and the OR for
      Blacks having undocumented vaccination was 1.95 (P < or = .001). Stratified
      analyses confirmed persistent racial disparities among subpopulations.
      CONCLUSIONS: Racial disparities exist in vaccination coverage among US nursing
      home residents. Targeted interventions to improve vaccination coverage for
      minority nursing-home residents are warranted.

PMID- 20147675
TI  - Prejudice & policy: racial discrimination in the Union Army disability pension
      system, 1865-1906.
AB  - The Union Army disability pension was an early experiment in colorblind social
      policy. However, it shortchanged Blacks in 2 ways. First, the law was unable to
      account for the challenges Blacks faced in proving their eligibility because of
      the legacy of slavery and discrimination against Black troops during the Civil
      War. Second, the increasing leniency accorded White soldiers by the Pension
      Bureau was not extended in the same measure to Blacks. Active discrimination
      against Blacks resulted in part from local discretion, evidenced by the
      significantly lower approval rates for both White and Black veterans in the
      South. Furthermore, when Whites and Blacks claimed disabilities that were easily
      verifiable, outcomes were similar, but when verification required a degree of
      trust, Blacks fared considerably worse than Whites.

PMID- 20147676
TI  - Coverage and framing of racial and ethnic health disparities in US newspapers,
      1996-2005.
AB  - OBJECTIVES: We examined how causes of and solutions to racial/ethnic health
      disparities are covered and framed in newspapers over time. METHODS: We used
      LexisNexis to identify articles on racial/ethnic health disparities published
      from 1996 through 2005 in 40 US newspapers. We coded articles for diseases and
      racial/ethnic groups mentioned; whether causes and solutions were framed as
      genetic, behavioral, health care, or societal responsibility; and whether a
      social-justice rationale for eliminating racial/ethnic health disparities was
      invoked. RESULTS: We identified 3823 racial/ethnic health disparity articles.
      Coverage peaked in 1998 and has declined since. Disparities in HIV/AIDS,
      cardiovascular disease, and cancer generated the most coverage. Articles focused
      primarily on African Americans. Only 30% of articles provided causal or solution
      explanations, with academic researchers providing the most causal explanations
      and advocacy groups providing the most solutions. For both causes and solutions,
      behavioral explanations dominated the discourse, followed by societal, health
      care, and genetic explanations. Only 4% of articles invoked a social-justice
      rationale. CONCLUSIONS: The dominance of behavioral explanations may limit public
      support for policy solutions to eliminate racial/ethnic health disparities.
      Future research should examine the design and dissemination of effective messages
      about the social determinants of health.

PMID- 20147677
TI  - The moral problem of health disparities.
AB  - Health disparities exist along lines of race/ethnicity and socioeconomic class in
      US society. I argue that we should work to eliminate these health disparities
      because their existence is a moral wrong that needs to be addressed. Health
      disparities are morally wrong because they exemplify historical injustices.
      Contractarian ethics, Kantian ethics, and utilitarian ethics all provide
      theoretical justification for viewing health disparities as a moral wrong, as do
      several ethical principles of primary importance in bioethics. The moral
      consequences of health disparities are also troubling and further support the
      claim that these disparities are a moral wrong. The Universal Declaration of
      Human Rights provides additional support that health disparities are a moral
      wrong, as does an analogy with the generally accepted duty to provide equal
      access to education. In this article, I also consider and respond to 3 objections
      to my thesis.

PMID- 20147678
TI  - Under the skin: using theories from biology and the social sciences to explore
      the mechanisms behind the black-white health gap.
AB  - Equity and social well-being considerations make Black-White health disparities
      an area of important concern. Although previous research suggests that
      discrimination- and poverty-related stressors play a role in African American
      health outcomes, the mechanisms are unclear. Allostatic load is a concept that
      can be employed to demonstrate how environmental stressors, including
      psychosocial ones, may lead to a cumulative physiological toll on the body. We
      discuss both the usefulness of this framework for understanding how
      discrimination can lead to worse health among African Americans, and the
      challenges for conceptualizing biological risk with existing data and methods. We
      also contrast allostatic load with theories of historical trauma such as
      posttraumatic slavery syndrome. Finally, we offer our suggestions for future
      interdisciplinary research on health disparities.

PMID- 20147679
TI  - Critical Race Theory, race equity, and public health: toward antiracism praxis.
AB  - Racial scholars argue that racism produces rates of morbidity, mortality, and
      overall well-being that vary depending on socially assigned race. Eliminating
      racism is therefore central to achieving health equity, but this requires new
      paradigms that are responsive to structural racism's contemporary influence on
      health, health inequities, and research. Critical Race Theory is an emerging
      transdisciplinary, race-equity methodology that originated in legal studies and
      is grounded in social justice. Critical Race Theory's tools for conducting
      research and practice are intended to elucidate contemporary racial phenomena,
      expand the vocabulary with which to discuss complex racial concepts, and
      challenge racial hierarchies. We introduce Critical Race Theory to the public
      health community, highlight key Critical Race Theory characteristics (race
      consciousness, emphases on contemporary societal dynamics and socially
      marginalized groups, and praxis between research and practice) and describe
      Critical Race Theory's contribution to a study on racism and HIV testing among
      African Americans.

PMID- 20147680
TI  - Results of a pilot diabetes prevention intervention in East Harlem, New York
      City: Project HEED.
AB  - OBJECTIVES: Our community-academic partnership employed community-based
      participatory research to develop and pilot a simple, peer-led intervention to
      promote weight loss, which can prevent diabetes and eliminate racial/ethnic
      disparities in incident diabetes among overweight adults with prediabetes.
      METHODS: We recruited overweight adults at community sites, performed oral
      glucose tolerance testing to identify persons with blood glucose levels in the
      prediabetes range, and randomized eligible people to a peer-led lifestyle
      intervention group or delayed intervention in 1 year. Outcomes, including weight,
      blood pressure, and health behaviors, were measured at baseline and 3, 6, and 12
      months. RESULTS: More than half of those tested (56%, or 99 of 178) had
      prediabetes and enrolled in the study. Participants were predominantly Spanish
      speaking, low-income, undereducated women. The intervention group lost
      significantly more weight than the control group and maintained weight loss at 12
      months (7.2 versus 2.4 pounds; P < .01). One fourth (24 of 99) of participants
      progressed to diabetes. CONCLUSIONS: In underserved minority communities,
      prediabetes prevalence may be higher than previously reported. Low-cost,
      community-based interventions can succeed in encouraging weight loss to prevent
      diabetes.

PMID- 20147681
TI  - HIV-tuberculosis coinfection in Southern California: evaluating disparities in
      disease burden.
AB  - OBJECTIVES: We sought to understand tuberculosis (TB) and HIV coinfection trends
      in San Diego County, California, and to identify associations between
      sociodemographic risk factors and TB and HIV coinfection. METHODS: We analyzed TB
      surveillance data from 1993 through 2007. TB cases were grouped by HIV status:
      positive, negative, or unknown. We used Poisson regression to estimate trends and
      tested associations between TB and HIV coinfection and sociodemographic risk
      factors with polychotomous logistic regression. RESULTS: Of 5172 TB cases, 8.8%
      were also infected with HIV. Incidence of coinfected cases did not change
      significantly over the period studied, but the proportion of cases among
      Hispanics increased significantly, whereas cases among non-Hispanic Whites and
      Blacks decreased. TB cases with HIV coinfection were significantly more likely to
      be Hispanic, male, injection drugs users, and aged 30 to 49 years, relative to
      cases with TB disease only. CONCLUSIONS: The burden of TB and HIV in San Diego
      has shifted to Hispanics in the last decade. To address this health disparity,
      binational TB and HIV prevention efforts are needed.

PMID- 20147683
TI  - The impact of prenatal WIC participation on infant mortality and racial
      disparities.
AB  - OBJECTIVES: We assessed the value of Special Supplemental Nutrition Program for
      Women, Infants, and Children (WIC) services as a public health intervention
      seeking to improve birth outcomes and reduce racial disparities. METHODS: We
      compared the infant mortality rate (IMR) per 1000 live births and percentage of
      preterm births overall and by race for prenatal WIC versus non-WIC participants
      in Hamilton County, Ohio, from 2005 to 2008. RESULTS: The IMR was lower for WIC
      participants than for non-WIC participants (8.0 vs 10.6; P = .04). For African
      Americans, the IMR of WIC participants was much lower than that of non-WIC
      participants (9.6 vs 21.0; P < .001). For Whites, IMR and preterm birth rates
      were not improved by WIC participation; however, there was a higher rate of
      maternal smoking among Whites. The racial disparity in IMR was dramatically
      reduced in WIC participants (9.6 for African Americans vs 6.7 for Whites; P =
      .14) as compared with non-WIC participants (21.0 for African Americans vs 7.8 for
      Whites; P < .001). CONCLUSIONS: Prenatal WIC participation is associated with
      significant improvements in African American IMR. WIC participation reduces
      racial disparities in IMR between African Americans and Whites.

PMID- 20147682
TI  - Disparate inclusion of older adults in clinical trials: priorities and
      opportunities for policy and practice change.
AB  - Older adults are vastly underrepresented in clinical trials in spite of
      shouldering a disproportionate burden of disease and consumption of prescription
      drugs and therapies, restricting treatments' generalizability, efficacy, and
      safety. Eliminating Disparities in Clinical Trials, a national initiative
      comprising a stakeholder network of researchers, community advocates,
      policymakers, and federal representatives, undertook a critical analysis of older
      adults' structural barriers to clinical trial participation. We present practice
      and policy change recommendations emerging from this process and their rationale,
      which spanned multiple themes: (1) decision making with cognitively impaired
      patients; (2) pharmacokinetic differences and physiological age; (3) health
      literacy, communication, and aging; (4) geriatric training; (5) federal
      monitoring and accountability; (6) clinical trial costs; and (7) cumulative
      effects of aging and ethnicity.

PMID- 20147684
TI  - Generating political priority to tackle health disparities: a case study in the
      Dutch city of The Hague.
AB  - OBJECTIVES: We sought to study the factors that determined the success of a
      recent initiative to generate political priority for the problem of health
      disparities in the city of The Hague, the Netherlands. METHODS: Our study had a
      prospective design. The qualitative data collection included interviews, document
      analyses, and observations. RESULTS: Crucial for the success of this initiative
      was the presence of powerful and credible actors. These actors effectively
      presented scientific evidence on health disparities and framed the issue in the
      light of shared values, priorities, and policy principles. Finally, their actions
      were supported by the national context, including the availability of national
      scientific research on health disparities. CONCLUSIONS: The project in The Hague
      shows that political priority for tackling health disparities can be generated at
      a local level. Key factors included framing the issue in the light of shared
      values and framing the problem and the solution as in line with existing policy
      principles.

PMID- 20147685
TI  - Oral health disparities and psychosocial correlates of self-rated oral health in
      the National Survey of American Life.
AB  - OBJECTIVES: We sought to better understand the determinants of oral health
      disparities by examining individual-level psychosocial stressors and resources
      and self-rated oral health in nationally representative samples of Black
      American, Caribbean Black, and non-Hispanic White adults. METHODS: We conducted
      logistic regression analyses on fair or poor versus better oral health using data
      from the National Survey of American Life (n = 6082). RESULTS: There were no
      significant racial differences. Overall, 28% of adults reported having fair or
      poor oral health. Adults with lower income and less than a high school education
      were each about 1.5 times as likely as other adults to report fair or poor oral
      health. Higher levels of chronic stress, depressive symptoms, and material
      hardship were associated with fair or poor oral health. Adults living near more
      neighborhood resources were less likely to report fair or poor oral health.
      Higher levels of self-esteem and mastery were protective, and more-religious
      adults were also less likely to report fair or poor oral health. CONCLUSIONS:
      Social gradients in self-rated oral health were found, and they have implications
      for developing interventions to address oral health disparities.

PMID- 20147686
TI  - Translating research evidence into practice to reduce health disparities: a
      social determinants approach.
AB  - Translating research evidence to reduce health disparities has emerged as a
      global priority. The 2008 World Health Organization Commission on Social
      Determinants of Health recently urged that gaps in health attributable to
      political, social, and economic factors should be closed in a generation.
      Achieving this goal requires a social determinants approach to create public
      health systems that translate efficacy documented by research into effectiveness
      in the community. We review the scope, definitions, and framing of health
      disparities and explore local, national, and global programs that address
      specific health disparities. Such efforts translate research evidence into real
      world settings and harness collaborative social action for broad-scale,
      sustainable change.

PMID- 20147687
TI  - Customizing survey instruments and data collection to reach Hispanic/Latino
      adults in border communities in Texas.
AB  - OBJECTIVES: We sought to modify an instrument and to use it to collect
      information on smoking knowledge, attitudes, beliefs, and behaviors among
      Hispanics/Latinos, and to adapt survey methods to obtain high participation
      levels. Methods. Promotoras (outreach workers) conducted face-to-face interviews
      with 1485 Hispanic adults (July 2007-April 2008). The project team used GeoFrame
      field enumeration methods to develop a sampling frame from households in randomly
      selected colonias (residential areas along the Texas-Mexico border that may lack
      some basic necessities (e.g. portable water), in El Paso, Texas. RESULTS: The
      revised questionnaire included 36 unchanged items from the State Adult Tobacco
      Survey, 7 modified items, and 17 new items focusing on possible culturally
      specific quitting methods, secondhand smoke issues, and attitudes and knowledge
      about tobacco use that might be unique for Hispanic/Latino groups. The
      eligibility rate was 90.2%, and the conservative combined completed screener and
      interview response rate was 80.0%. CONCLUSIONS: Strategic, targeted, carefully
      designed methods and surveys can achieve high reach and response rates in hard-to
      reach populations. Similar procedures could be used to obtain cooperation of
      groups who may not be accessible with traditional methods.

PMID- 20147688
TI  - Explaining ethnic disparities in patient safety: a qualitative analysis.
AB  - OBJECTIVES: We explored characteristics of in-hospital care and treatment of
      immigrant patients to better understand the processes underlying ethnic
      disparities in patient safety. METHODS: We conducted semistructured interviews
      with care providers regarding patient safety events involving immigrant patients
      in in-hospital medical care and treatment, for a total of 30 cases. Interviews
      were transcribed and qualitatively analyzed with a framework method. RESULTS:
      Three key patterns were identified from the analysis. Patient safety events occur
      because of (1) inappropriate responses by health care providers to objective
      characteristics of immigrant patients, such as low Dutch language proficiency,
      lack of health insurance, or genetic conditions; (2) misunderstandings between
      patients and care providers because of differences in illness perceptions and
      expectations about care and treatment; and (3) inappropriate care because of
      providers' prejudices against or stereotypical ideas regarding immigrant
      patients. CONCLUSIONS: Our findings suggest that organizational and health
      professional practices contribute to the higher risk of patient safety events.
      Descriptive epidemiological research is needed to explore the impact of the 3
      patterns on patient safety.

PMID- 20147689
TI  - Using motivational interviewing in HIV field outreach with young African American
      men who have sex with men: a randomized clinical trial.
AB  - OBJECTIVES: We sought to determine whether field outreach with motivational
      interviewing, as compared with traditional field outreach, leads to increases in
      HIV counseling and testing and rates of return for test results among young
      African American men who have sex with men (MSM). METHODS: In a randomized, 2
      group, repeated-measures design, 96 young African American MSM completed a
      motivational interviewing-based field outreach session and 92 young African
      American MSM completed a traditional field outreach session. The percentages of
      participants agreeing to traditional HIV counseling and testing (an oral swab of
      the cheek) and returning for test results were the primary outcome measures.
      RESULTS: More of the participants in the motivational interviewing condition than
      the control condition received HIV counseling and testing (49% versus 20%;
      chi(2)(1) = 17.94; P = .000) and returned for test results (98% versus 72%;
      chi(2)(1) = 10.22; P = .001). CONCLUSIONS: The addition of motivational
      interviewing to field outreach is effective in encouraging high-risk young
      African American MSM to learn their HIV status. Also, peer outreach workers can
      be effectively trained to reduce health disparities by providing evidence-based
      brief counseling approaches targeting high-risk minority populations.

PMID- 20147690
TI  - Finding synergy: reducing disparities in health by modifying multiple
      determinants.
AB  - Although researchers acknowledge that health disparities have multiple
      determinants, most recommendations for reducing inequities focus on a single
      approach. We suggest integrating 2 approaches for reducing disparities: improving
      access to primary care and updating and more vigorously enforcing consumer and
      environmental protection laws. This strategy could reduce the main causes of
      disparities, such as chronic diseases and injuries; win public and policymaker
      support; and provide a cost-effective start for achieving equity. Most of the
      scientific knowledge needed to implement this strategy exists, thus years of
      additional research would not be needed. Developing targeted regulatory and
      health care policies to reduce deaths from chronic diseases and injuries would be
      a major step forward in eliminating health disparities in the United States.

PMID- 20147691
TI  - HIV counseling and testing among Hispanics at CDC-funded sites in the United
      States, 2007.
AB  - OBJECTIVES: We sought to determine whether Hispanic-White HIV testing disparities
      exist and to identify characteristics associated with newly diagnosed HIV among
      Hispanics. METHODS: We used 2007 HIV Counseling and Testing System data to
      compare test-level records of Hispanics and non-Hispanic Whites, and we conducted
      a multivariate logistic regression analysis to identify characteristics
      associated with newly diagnosed HIV. RESULTS: Relative to Whites, Hispanics were
      more likely to have had a positive HIV test result (1.2% versus 0.8%), to have
      newly diagnosed HIV (0.8% versus 0.6%), and to have test results returned and
      receive posttest counseling more than 2 weeks after testing (24.3% versus 21.5%).
      Newly diagnosed HIV among Hispanics was most strongly associated with being a man
      who has sex with men (MSM; adjusted odds ratio [AOR] = 6.8; 95% confidence
      interval [CI] = 6.1, 7.6), being both an MSM and an injection drug user (AOR =
      3.7; 95% CI = 2.6, 5.3), and being aged 40 to 49 years (AOR = 6.4; 95% CI = 4.9,
      8.2). CONCLUSIONS: Hispanic-White disparities exist with respect to rates of
      positive HIV test results and late return of results. HIV prevention strategies
      such as rapid testing should focus on Hispanic MSM.

PMID- 20147692
TI  - Reaching Spanish-speaking smokers: state-level evidence of untapped potential for
      QuitLine utilization.
AB  - OBJECTIVES: We examined the effects of a Spanish-language media campaign on the
      reach and outcomes of a state-sponsored QuitLine among Latino smokers. METHODS:
      In this quasiexperimental (2-group, pre-post) study, we analyzed data from
      Colorado QuitLine callers before (April-August 2007) and during (September
      November 2007) the media campaign. Call volume, service utilization, and quit
      rates at 7-month follow-up were compared between Latino (n = 243) and non-Latino
      (n = 527) callers. RESULTS: QuitLine calls increased among Latinos during the
      campaign by 57.6% (1169 vs 1842 in 3-month periods). Compared with precampaign
      Latino study respondents, Latino respondents during the campaign were
      significantly younger (younger than 45 years), more often Spanish speaking,
      uninsured, and less educated. Among Latino enrollees, program completion and
      nicotine replacement therapy use were similar before and during the campaign, and
      quit rates during the campaign improved marginally to significantly (7-day
      abstinence: 29.6% vs 41.0%, P = .07; 6-month abstinence: 9.6% vs 18.8%, P = .04).
      CONCLUSIONS: A well-designed, statewide Spanish-language media campaign increased
      QuitLine reach and improved cessation outcomes among a young Latino population of
      low socioeconomic status. QuitLine-supported cessation can be increased among
      these smokers.

PMID- 20147694
TI  - Linking science and policy through community-based participatory research to
      study and address health disparities.
AB  - With its commitment to balancing research and action, community-based
      participatory research (CBPR) is well suited to efforts at the intersections of
      science, practice, and policy to eliminate health disparities. Drawing on a
      larger study, we use 2 case studies to highlight the role of CBPR in helping
      achieve policy changes promoting, respectively, access to healthy foods (Bayview,
      San Francisco, CA) and higher air quality standards (Harlem, New York, NY). We
      then present facilitating factors and challenges faced across all 10 case studies
      from the larger study. Although we underscore the importance of analyzing
      contribution rather than claiming attribution in policy-focused work, CBPR's
      attention to both the distributive and the procedural justice necessary for
      eliminating health disparities may make it a particularly relevant approach in
      such work.

PMID- 20147693
TI  - Socioeconomic disparities in health in the United States: what the patterns tell
      us.
AB  - OBJECTIVES: We aimed to describe socioeconomic disparities in the United States
      across multiple health indicators and socioeconomic groups. METHODS: Using recent
      national data on 5 child (infant mortality, health status, activity limitation,
      healthy eating, sedentary adolescents) and 6 adult (life expectancy, health
      status, activity limitation, heart disease, diabetes, obesity) health indicators,
      we examined indicator rates across multiple income or education categories,
      overall and within racial/ethnic groups. RESULTS: Those with the lowest income
      and who were least educated were consistently least healthy, but for most
      indicators, even groups with intermediate income and education levels were less
      healthy than the wealthiest and most educated. Gradient patterns were seen often
      among non-Hispanic Blacks and Whites but less consistently among Hispanics.
      CONCLUSIONS: Health in the United States is often, though not invariably,
      patterned strongly along both socioeconomic and racial/ethnic lines, suggesting
      links between hierarchies of social advantage and health. Worse health among the
      most socially disadvantaged argues for policies prioritizing those groups, but
      pervasive gradient patterns also indicate a need to address a wider socioeconomic
      spectrum-which may help garner political support. Routine health reporting should
      examine socioeconomic and racial/ethnic disparity patterns, jointly and
      separately.

PMID- 20147695
TI  - Triangulating on success: innovation, public health, medical care, and cause
      specific US mortality rates over a half century (1950-2000).
AB  - To identify successes in improving America's health, we identified disease
      categories that appeared on vital statistics lists of leading causes of death in
      the US adult population in either 1950 or 2000, and that experienced at least a
      50% reduction in age-adjusted death rates from their peak level to their lowest
      point between 1950 and 2000. Of the 9 cause-of-death categories that achieved
      this 50% reduction, literature review suggests that 7 clearly required diffusion
      of new innovations through both public health and medical care channels. Our
      nation's health success stories are consistent with a triangulation model of
      innovation plus public health plus medical care, even when the 3 sectors have
      worked more in parallel than in partnership.

PMID- 20147696
TI  - Hidden breast cancer disparities in Asian women: disaggregating incidence rates
      by ethnicity and migrant status.
AB  - OBJECTIVES: We estimated trends in breast cancer incidence rates for specific
      Asian populations in California to determine if disparities exist by immigrant
      status and age. METHODS: To calculate rates by ethnicity and immigrant status, we
      obtained data for 1998 through 2004 cancer diagnoses from the California Cancer
      Registry and imputed immigrant status from Social Security Numbers for the 26% of
      cases with missing birthplace information. Population estimates were obtained
      from the 1990 and 2000 US Censuses. RESULTS: Breast cancer rates were higher
      among US- than among foreign-born Chinese (incidence rate ratio [IRR] = 1.84; 95%
      confidence interval [CI] = 1.72, 1.96) and Filipina women (IRR = 1.32; 95% CI =
      1.20, 1.44), but similar between US- and foreign-born Japanese women. US-born
      Chinese and Filipina women who were younger than 55 years had higher rates than
      did White women of the same age. Rates increased over time in most groups, as
      high as 4% per year among foreign-born Korean and US-born Filipina women. From
      2000-2004, the rate among US-born Filipina women exceeded that of White women.
      CONCLUSIONS: These findings challenge the notion that breast cancer rates are
      uniformly low across Asians and therefore suggest a need for increased awareness,
      targeted cancer control, and research to better understand underlying factors.

PMID- 20147697
TI  - Hepatitis B and hepatitis C prevalence and treatment referral among Asian
      Americans undergoing community-based hepatitis screening.
AB  - OBJECTIVES: We sought to identify cross-sectional hepatitis B virus (HBV) and HCV
      prevalence among Asian Americans at a community health fair and to assess
      referral rates. METHODS: We determined HBV prevalence with hepatitis B surface
      antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and
      antibodies to hepatitis B surface antigen (anti-HBs). We determined HCV
      prevalence with hepatitis C antibodies. Successful referral occurred when
      participants with HBV or HCV were contacted, medically evaluated, and given
      contact information of liver specialists for care. RESULTS: Of 202 people
      screened, 118 were Asian Americans (65 Chinese and 39 Vietnamese). Twelve had
      chronic HBV with positive HBsAg. However, chronic HBV prevalence increased from
      10.2% to 13.6% by concomitant HBsAg, anti-HBc, and anti-HBs testing. Prevalence
      of HCV was 6% overall but 15.4% among Vietnamese. Overall, 83% of patients with
      chronic HBV and 100% of patients with occult HBV or HCV were successfully
      referred. CONCLUSIONS: Concomitant HBsAg, anti-HBc, and anti-HBs testing permits
      diagnosis of chronic, occult HBV infections missed by testing with HBsAg alone.
      Persons identified with HBV or HCV at community health fairs can be successfully
      referred.

PMID- 20147698
TI  - Correlates of picuriste use in a sample of health-seeking Haitian immigrants and
      adult children of immigrants in Miami-Dade County, Florida.
AB  - OBJECTIVES: We explored covariates of the use of picuristes (traditional health
      workers with no formal medical training who provide intramuscular, subcutaneous,
      and intravenous injections, typically with nonsterile needles) in the Haitian
      community of Miami-Dade County, Florida. METHODS: We surveyed a community-based
      sample of 205 Haitian immigrants and adult children of Haitian immigrants.
      Through logistic regression analysis, we sought to corroborate the correlates of
      picuriste use identified in previous qualitative interviews of picuristes and
      their clients. RESULTS: Picuriste injections had been obtained by 17.6% of our
      respondents. After control for demographic characteristics, we found that
      participants who reported that a trusted person recommended a picuriste were 3.9
      times as likely as participants without a recommendation to have used a
      picuriste. Similarly, participants who believed that the benefits associated with
      picuriste use were worth any resulting problems were 4.5 times as likely as those
      without this belief to have patronized a picuriste. CONCLUSIONS: A significant
      minority of our sample patronized picuristes. Our data identified factors
      associated with picuriste use and shed light on a frequently hidden cultural
      health behavior.

PMID- 20147700
TI  - A novel KIR-associated function: evidence that CpG DNA uptake and shuttling to
      early endosomes is mediated by KIR3DL2.
AB  - Human natural killer (NK) cells express Toll-like receptor 9 (TLR9) transcript
      and, upon exposure to microbial CpG oligodeoxynucleotide (ODN), release cytokines
      and kill target cells. Here we show that NK cell treatment with CpG ODN results
      in down-modulation of KIR3DL2 inhibitory receptor from the cell surface and in
      its cointernalization with CpG ODN. CpG ODN-induced interferon-gamma (IFN-gamma)
      release is mostly confined to KIR3DL2(+) NK cells, thus suggesting a crucial role
      of KIR3DL2 in CpG ODN-mediated NK responses. Using soluble receptor molecules, we
      demonstrate the direct binding of KIR3DL2 to ODNs and we show that the D0 domain
      is involved primarily in this interaction. KIR3DL2 modulation is also induced in
      malignant cells of Sezary cutaneous T-cell lymphoma, a disease in which KIR3DL2
      represents a typical marker of malignant T cells. Confocal microscopy analysis
      suggests that, in human NK cells, CpG ODN can encounter TLR9 in early endosomes
      after being shuttled to these sites by KIR3DL2, which functions as a CpG ODN
      receptor at the cell surface. This novel KIR-associated function emphasizes the
      antimicrobial role of NK cells in the course of infection.

PMID- 20147699
TI  - Suppression of adaptive immune responses during primary SIV infection of sabaeus
      African green monkeys delays partial containment of viremia but does not induce
      disease.
AB  - One of the most puzzling observations in HIV research is the lack of
      pathogenicity in most nonhuman primate species that are natural hosts of simian
      immunodeficiency virus (SIV) infection. Despite this, natural hosts experience a
      level of viremia similar to humans infected with HIV or macaques infected with
      SIV. To determine the role of adaptive immune responses in viral containment and
      lack of disease, we delayed the generation of cellular and humoral immune
      responses by administering anti-CD8- and anti-CD20 lymphocyte-depleting
      antibodies to sabaeus African green monkeys (Chlorocebus sabaeus) before
      challenge with SIV(sab9315BR). In vivo lymphocyte depletion during primary
      infection resulted in a brief elevation of viremia but not in disease. Based on
      the magnitude and timing of SIV-specific CD8(+) T-cell responses in the
      lymphocyte-depleted animals, CD8(+) T-cell responses appear to contribute to
      viral containment in natural hosts. We found no evidence for a contribution of
      humoral immune responses in viral containment. These studies indicate that
      natural hosts have developed mechanisms in addition to classic adaptive immune
      responses to cope with this lentiviral infection. Thus, adaptive immune responses
      in natural hosts appear to be less critical for viral containment than in HIV
      infection.

PMID- 20147701
TI  - "City life in relation to tuberculosis: a plea for better surroundings for
      factories and better homes for the working classes." American Journal of Public
      Health 3, no. 9 (1913): 903-914.

PMID- 20147702
TI  - Comparison of the liquid-ordered bilayer phases containing cholesterol or 7
      dehydrocholesterol in modeling Smith-Lemli-Opitz syndrome.
AB  - The phase behavior of egg sphingomyelin (ESM) mixtures with cholesterol or 7
      dehydrocholesterol (7-DHC) has been investigated by independent methods:
      fluorescence microscopy, X-ray diffraction, and electron spin resonance
      spectroscopy. In giant vesicles, cholesterol-enriched domains appeared as large
      and clearly delineated domains assigned to a liquid-ordered (Lo) phase. The
      domains containing 7-DHC were smaller and had more diffuse boundaries. Separation
      of a gel phase assigned by X-ray examination to pure sphingomyelin domains
      coexisting with sterol-enriched domains was observed at temperatures less than 38
      degrees C in binary mixtures containing 10-mol% sterol. At higher sterol
      concentrations, the coexistence of liquid-ordered and liquid-disordered phases
      was evidenced in the temperature range 20 degrees -50 degrees C. Calculated
      electron density profiles indicated the location of 7-DHC was more loosely
      defined than cholesterol, which is localized precisely at a particular depth
      along the bilayer normal. ESR spectra of spin-labeled fatty acid partitioned in
      the liquid-ordered component showed a similar, high degree of order for both
      sterols in the center of the bilayer, but it was higher in the coexisting
      disordered phase for 7-DHC. The differences detected in the models of the lipid
      membrane matrix are said to initiate the deleterious consequences of the Smith
      Lemli-Opitz syndrome.

PMID- 20147704
TI  - Forging ahead--embracing the "reconciliation" option for reform.

PMID- 20147703
TI  - Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a
      retinoic acid-metabolizing enzyme in rat liver.
AB  - Several cytochrome P450 (CYP) enzymes catalyze the C4-hydroxylation of retinoic
      acid (RA), a potent inducer of cell differentiation and an agent in the treatment
      of several diseases. Here, we have characterized CYP2C22, a member of the rat
      CYP2C family with homology to human CYP2C8 and CYP2C9. CYP2C22 was expressed
      nearly exclusively in hepatocytes, where it was one of the more abundant mRNAs
      transcripts. In H-4-II-E rat hepatoma cells, CYP2C22 mRNA was upregulated by all
      trans (at)-RA, and Am580, a nonmetabolizable analog of at-RA. In comparison, in
      primary human hepatocytes, at-RA increased CYP2C9 but not CYP2C8 mRNA. Analysis
      of the CYP2C22 promoter region revealed a RA response element (5'-GGTTCA-(n)5
      AGGTCA-3') in the distal flanking region, which bound the nuclear hormone
      receptors RAR and RXR and which was required for transcriptional activation
      response of this promoter to RA in CYP2C22-luciferase-transfected RA-treated
      HepG2 cells. The cDNA-expressed CYP2C22 protein metabolized [3H]at-RA to more
      polar metabolites. While long-chain polyunsaturated fatty acids competed, 9-cis
      RA was a stronger competitor. Our studies demonstrate that CYP2C22 is a high
      abundance, retinoid-inducible, hepatic P450 with the potential to metabolize at
      RA, providing additional insight into the role of the CYP2C gene family in
      retinoid homeostasis.

PMID- 20147705
TI  - Can the states nullify health care reform?

PMID- 20147706
TI  - Throwing down the gauntlet--televised, bipartisan health care discussions.

PMID- 20147707
TI  - AIDS in America--forgotten but not gone.

PMID- 20147708
TI  - Genetic susceptibility to stuttering.

PMID- 20147710
TI  - Images in clinical medicine. Cutaneous leishmaniasis.

PMID- 20147709
TI  - Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering.
AB  - BACKGROUND: Stuttering is a disorder of unknown cause characterized by
      repetitions, prolongations, and interruptions in the flow of speech. Genetic
      factors have been implicated in this disorder, and previous studies of stuttering
      have identified linkage to markers on chromosome 12. METHODS: We analyzed the
      chromosome 12q23.3 genomic region in consanguineous Pakistani families, some
      members of which had nonsyndromic stuttering and in unrelated case and control
      subjects from Pakistan and North America. RESULTS: We identified a missense
      mutation in the N-acetylglucosamine-1-phosphate transferase gene (GNPTAB), which
      encodes the alpha and beta catalytic subunits of GlcNAc-phosphotransferase (GNPT
      [EC 2.7.8.15]), that was associated with stuttering in a large, consanguineous
      Pakistani family. This mutation occurred in the affected members of approximately
      10% of Pakistani families studied, but it occurred only once in 192 chromosomes
      from unaffected, unrelated Pakistani control subjects and was not observed in 552
      chromosomes from unaffected, unrelated North American control subjects. This and
      three other mutations in GNPTAB occurred in unrelated subjects with stuttering
      but not in control subjects. We also identified three mutations in the GNPTG
      gene, which encodes the gamma subunit of GNPT, in affected subjects of Asian and
      European descent but not in control subjects. Furthermore, we identified three
      mutations in the NAGPA gene, which encodes the so-called uncovering enzyme, in
      other affected subjects but not in control subjects. These genes encode enzymes
      that generate the mannose-6-phosphate signal, which directs a diverse group of
      hydrolases to the lysosome. Deficits in this system are associated with the
      mucolipidoses, rare lysosomal storage disorders that are most commonly associated
      with bone, connective tissue, and neurologic symptoms. CONCLUSIONS:
      Susceptibility to nonsyndromic stuttering is associated with variations in genes
      governing lysosomal metabolism.

PMID- 20147711
TI  - Israeli views of health care reform.

PMID- 20147712
TI  - Is it always wrong to perform futile CPR?

PMID- 20147713
TI  - Failing to thrive.

PMID- 20147714
TI  - Childhood obesity, other cardiovascular risk factors, and premature death.
AB  - BACKGROUND: The effect of childhood risk factors for cardiovascular disease on
      adult mortality is poorly understood. METHODS: In a cohort of 4857 American
      Indian children without diabetes (mean age, 11.3 years; 12,659 examinations) who
      were born between 1945 and 1984, we assessed whether body-mass index (BMI),
      glucose tolerance, and blood pressure and cholesterol levels predicted premature
      death. Risk factors were standardized according to sex and age. Proportional
      hazards models were used to assess whether each risk factor was associated with
      time to death occurring before 55 years of age. Models were adjusted for baseline
      age, sex, birth cohort, and Pima or Tohono O'odham Indian heritage. RESULTS:
      There were 166 deaths from endogenous causes (3.4% of the cohort) during a median
      follow-up period of 23.9 years. Rates of death from endogenous causes among
      children in the highest quartile of BMI were more than double those among
      children in the lowest BMI quartile (incidence-rate ratio, 2.30; 95% confidence
      interval [CI], 1.46 to 3.62). Rates of death from endogenous causes among
      children in the highest quartile of glucose intolerance were 73% higher than
      those among children in the lowest quartile (incidence-rate ratio, 1.73; 95% CI,
      1.09 to 2.74). No significant associations were seen between rates of death from
      endogenous or external causes and childhood cholesterol levels or systolic or
      diastolic blood-pressure levels on a continuous scale, although childhood
      hypertension was significantly associated with premature death from endogenous
      causes (incidence-rate ratio, 1.57; 95% CI, 1.10 to 2.24). CONCLUSIONS: Obesity,
      glucose intolerance, and hypertension in childhood were strongly associated with
      increased rates of premature death from endogenous causes in this population. In
      contrast, childhood hypercholesterolemia was not a major predictor of premature
      death from endogenous causes.

PMID- 20147715
TI  - Stent graft versus balloon angioplasty for failing dialysis-access grafts.
AB  - BACKGROUND: The leading cause of failure of a prosthetic arteriovenous
      hemodialysis-access graft is venous anastomotic stenosis. Balloon angioplasty,
      the first-line therapy, has a tendency to lead to subsequent recoil and
      restenosis; however, no other therapies have yet proved to be more effective.
      This study was designed to compare conventional balloon angioplasty with an
      expanded polytetrafluoroethylene endovascular stent graft for revision of venous
      anastomotic stenosis in failing hemodialysis grafts. METHODS: We conducted a
      prospective, multicenter trial, randomly assigning 190 patients who were
      undergoing hemodialysis and who had a venous anastomotic stenosis to undergo
      either balloon angioplasty alone or balloon angioplasty plus placement of the
      stent graft. Primary end points included patency of the treatment area and
      patency of the entire vascular access circuit. RESULTS: At 6 months, the
      incidence of patency of the treatment area was significantly greater in the stent
      graft group than in the balloon-angioplasty group (51% vs. 23%, P<0.001), as was
      the incidence of patency of the access circuit (38% vs. 20%, P=0.008). In
      addition, the incidence of freedom from subsequent interventions at 6 months was
      significantly greater in the stent-graft group than in the balloon-angioplasty
      group (32% vs. 16%, P=0.03 by the log-rank test and P=0.04 by the Wilcoxon rank
      sum test). The incidence of binary restenosis at 6 months was greater in the
      balloon-angioplasty group than in the stent-graft group (78% vs. 28%, P<0.001).
      The incidences of adverse events at 6 months were equivalent in the two treatment
      groups, with the exception of restenosis, which occurred more frequently in the
      balloon-angioplasty group (P<0.001). CONCLUSIONS: In this study, percutaneous
      revision of venous anastomotic stenosis in patients with a prosthetic
      hemodialysis graft was improved with the use of a stent graft, which appears to
      provide longer-term and superior patency and freedom from repeat interventions
      than standard balloon angioplasty. (ClinicalTrials.gov number, NCT00678249.)

PMID- 20147716
TI  - Single-dose liposomal amphotericin B for visceral leishmaniasis in India.
AB  - BACKGROUND: Some 50% of patients with visceral leishmaniasis (kala-azar)
      worldwide live in the Indian state of Bihar. Liposomal amphotericin B is an
      effective treatment when administered in short courses. We wanted to determine
      whether the efficacy of a single infusion of liposomal amphotericin B was
      inferior to conventional parenteral therapy, consisting of 15 alternate-day
      infusions of amphotericin B deoxycholate. METHODS: In this open-label study, we
      randomly assigned 412 patients in a 3:1 ratio to receive either liposomal
      amphotericin B (liposomal-therapy group) or amphotericin B deoxycholate
      (conventional-therapy group). Liposomal amphotericin B (at a dose of 10 mg per
      kilogram of body weight) was given once, and patients were discharged home 24
      hours later. Amphotericin B deoxycholate, which was administered in 15 infusions
      of 1 mg per kilogram, was given every other day during a 29-day hospitalization.
      We determined the cure rate 6 months after treatment. RESULTS: A total of 410
      patients--304 of 304 patients (100%) in the liposomal-therapy group and 106 of
      108 patients (98%) in the conventional-therapy group--had apparent cure responses
      at day 30. Cure rates at 6 months were similar in the two groups: 95.7% (95%
      confidence interval [CI], 93.4 to 97.9) in the liposomal-therapy group and 96.3%
      (95% CI, 92.6 to 99.9) in the conventional-therapy group. Adverse events in the
      liposomal-therapy group were infusion-related fever or rigors (in 40%) and
      increased anemia or thrombocytopenia (in 2%); such events in the conventional
      therapy group were fever or rigors (in 64%), increased anemia (in 19%), and
      hypokalemia (in 2%). Nephrotoxicity or hepatotoxicity developed in no more than
      1% of patients in each group. CONCLUSIONS: A single infusion of liposomal
      amphotericin B was not inferior to and was less expensive than conventional
      therapy with amphotericin B deoxycholate. (ClinicalTrials.gov number,
      NCT00628719.)

PMID- 20147717
TI  - Long-term results of hypofractionated radiation therapy for breast cancer.
AB  - BACKGROUND: The optimal fractionation schedule for whole-breast irradiation after
      breast-conserving surgery is unknown. METHODS: We conducted a study to determine
      whether a hypofractionated 3-week schedule of whole-breast irradiation is as
      effective as a 5-week schedule. Women with invasive breast cancer who had
      undergone breast-conserving surgery and in whom resection margins were clear and
      axillary lymph nodes were negative were randomly assigned to receive whole-breast
      irradiation either at a standard dose of 50.0 Gy in 25 fractions over a period of
      35 days (the control group) or at a dose of 42.5 Gy in 16 fractions over a period
      of 22 days (the hypofractionated-radiation group). RESULTS: The risk of local
      recurrence at 10 years was 6.7% among the 612 women assigned to standard
      irradiation as compared with 6.2% among the 622 women assigned to the
      hypofractionated regimen (absolute difference, 0.5 percentage points; 95%
      confidence interval [CI], -2.5 to 3.5). At 10 years, 71.3% of women in the
      control group as compared with 69.8% of the women in the hypofractionated
      radiation group had a good or excellent cosmetic outcome (absolute difference,
      1.5 percentage points; 95% CI, -6.9 to 9.8). CONCLUSIONS: Ten years after
      treatment, accelerated, hypofractionated whole-breast irradiation was not
      inferior to standard radiation treatment in women who had undergone breast
      conserving surgery for invasive breast cancer with clear surgical margins and
      negative axillary nodes. (ClinicalTrials.gov number, NCT00156052.)

PMID- 20147718
TI  - The enigma of spontaneous preterm birth.

PMID- 20147719
TI  - Images in clinical medicine. Retinal arteriolar occlusions during a sickle cell
      crisis.

PMID- 20147720
TI  - Case records of the Massachusetts General Hospital. Case 4-2010. A 53-year-old
      man with arthralgias, oral ulcers, vision loss, and vocal-cord paralysis.

PMID- 20147721
TI  - Are children the future of type 2 diabetes prevention?

PMID- 20147722
TI  - Fistula first, stent graft second.

PMID- 20147723
TI  - How innate immunity can inhibit the release of HIV-1 from infected cells.

PMID- 20147724
TI  - Antibiotic prophylaxis and recurrent urinary tract infection in children.

PMID- 20147725
TI  - Norovirus gastroenteritis.

PMID- 20147726
TI  - Bacterial diarrhea.

PMID- 20147727
TI  - Phosphodiesterase inhibitors for pulmonary hypertension.

PMID- 20147728
TI  - FDA drug information that never reaches clinicians.

PMID- 20147729
TI  - Neuromuscular symptoms and elevated creatine kinase after statin withdrawal.

PMID- 20147730
TI  - Developmental programming: effect of prenatal steroid excess on intraovarian
      components of insulin signaling pathway and related proteins in sheep.
AB  - Prenatal testosterone (T) excess increases ovarian follicular recruitment,
      follicular persistence, insulin resistance, and compensatory hyperinsulinemia.
      Considering the importance of insulin in ovarian physiology, in this study, using
      prenatal T- and dihydrotestosterone (DHT, a nonaromatizable androgen)-treated
      female sheep, we tested the hypothesis that prenatal androgen excess alters the
      intraovarian insulin signaling cascade and metabolic mediators that have an
      impact on insulin signaling. Changes in ovarian insulin receptor (INSRB), insulin
      receptor substrate 1 (IRS1), mammalian target of rapamycin (MTOR),
      phosphatidylinositol 3-kinase (PIK3), peroxisome proliferator-activated receptor
      gamma (PPARG), and adiponectin proteins were determined at fetal (Days 90 and
      140), postpubertal (10 mo), and adult (21 mo) ages by immunohistochemistry.
      Results indicated that these proteins were expressed in granulosa, theca, and
      stromal compartments, with INSRB, IRS1, PPARG, and adiponectin increasing in
      parallel with advanced follicular differentiation. Importantly, prenatal T excess
      induced age-specific changes in PPARG and adiponectin expression, with increased
      PPARG expression evident during fetal life and decreased antral follicular
      adiponectin expression during adult life. Comparison of developmental changes in
      prenatal T and DHT-treated females found that the effects on PPARG were
      programmed by androgenic actions of T, whereas the effects on adiponectin were
      likely by its estrogenic action. These results suggest a role for PPARG in the
      programming of ovarian disruptions by prenatal T excess, including a decrease in
      antral follicular adiponectin expression and a contributory role for adiponectin
      in follicular persistence and ovulatory failure.

PMID- 20147731
TI  - Hepatocyte growth factor system in the mouse uterus: variation across the estrous
      cycle and regulation by 17-beta-estradiol and progesterone.
AB  - Hepatocyte growth factor (HGF) and its receptor MET have been implicated in
      uterine development, pregnancy, and endometrial disorders, such as endometriosis
      and carcinoma. In vitro studies have shown that HGF acts as a mitogen, motogen,
      and morphogen on endometrial epithelial cells. However, the expression and
      regulation of HGF and MET in the uteri of different species remain obscure. The
      present study aimed to investigate the changes of HGF, MET, and HGF activator
      (HGFA) expression in the uterine endometrium during the estrous cycle in mice and
      to explore estrogen and progesterone regulation of their expression. MKI67
      immunostaining was conducted to examine the association between HGF/MET
      expression and endometrial cell proliferation. Endometrial epithelial and stromal
      cells both expressed HGF, HGFA, and MET, but the cell type-specific patterns
      changed during the cycle. Estrogen and progesterone differentially regulated HGF,
      MET, and HGFA expression. Progesterone up-regulated their expression in the
      stroma and down-regulated their expression in the luminal epithelium, whereas 17
      beta-estradiol down-regulated their expression in the glandular epithelium. The
      pattern of HGF/MET overall correlated with that of MKI67. In conclusion, HGF,
      HGFA, and MET expression in mouse uterus changes during the estrous cycle in a
      stage-, cell type-, and compartment-specific manner under the influence of
      estrogen and progesterone. HGF likely plays a role in cyclic endometrial
      remodeling, such as cell proliferation via autocrine/paracrine mechanisms in
      mouse uterus.

PMID- 20147732
TI  - Characteristics of pulses of 13,14-dihydro-15-keto-prostaglandin f2alpha before,
      during, and after spontaneous luteolysis and temporal intrapulse relationships
      with progesterone concentrations in cattle.
AB  - Pulses of the prostaglandin F2alpha (PGF) metabolite 13,14-dihydro-15-keto-PGF
      (PGFM) were compared among heifers that were in the preluteolytic, luteolytic,
      and postluteolytic periods (n = 7 or 8 heifers/period). Hourly blood sampling was
      done in 18-h sessions 15, 16, or 17 days after ovulation. Hourly sampling and
      statistical identification of a PGFM pulse allowed novel comparisons of PGFM
      pulses among the three periods. Each period had a similar number of PGFM pulses
      (2.3 +/- 0.2). The pulses were more prominent during the luteolytic period than
      during the other periods, as indicated by significantly greater concentration for
      the peak and amplitude between nadir and peak. Significantly more fluctuations
      that did not meet the definition of a pulse occurred at the beginning of the
      preluteolytic period and end of the postluteolytic period than during the
      luteolytic period. The same nadir ended a pulse and began the next pulse in 85%
      of adjacent pulses. Seven heifers were selected objectively, based on a
      progesterone concentration >5 ng/ml at Hour -3 (Hour 0 = peak of PGFM pulse) and
      a progressive decrease in progesterone from Hours -3 to 0. Progesterone increased
      (P < 0.03) between Hours 0 and 1, remained at a mean plateau at Hours 1 and 2,
      and then decreased. Results support the hypothesis of a transient intrapulse
      rebound in progesterone during an individual PGFM pulse, but only during the
      first portion of luteolysis. These findings should be considered in future
      proposals on the mechanisms involved in the effects of PGF on progesterone
      concentrations.

PMID- 20147734
TI  - Enrichment of testicular gonocytes and genetic modification using lentiviral
      transduction in pigs.
AB  - Gonocytes are long-lived primary germ cells that reside in the center of
      seminiferous cords until differentiation into spermatogonia that drive
      spermatogenesis. In pigs, gonocytes have research value in the production of
      transgenic offspring through germline modification and transplantation. However,
      the rarity of pig gonocytes has raised the need for an efficient isolation
      method. Therefore, in this study we use components of extracellular matrix,
      laminin, fibronectin, and collagen type IV and their derivative, gelatin, to
      establish a negative selection system for functionally viable gonocytes in
      neonatal pig. We then demonstrate functional analysis with genetic modification
      using lentiviral transduction and successfully transplant the donor gonocytes,
      which colonized the seminiferous tubules of the recipient mouse. The most
      effective selection method was established by sequential use of laminin and
      gelatin, in which the purity of gonocytes was 80% and the recovery rate of
      gonocytes was 78%. The selected gonocytes were labeled with fluorescent dye PKH26
      and transplanted into busulfan-treated immunodeficient mouse testes. The
      fluorescent gonocytes colonized the recipient testes, and the resultant germ cell
      colonies were visible up to 4 mo after transplantation. When gonocytes were
      transplanted after transduction with an enhanced green fluorescent protein marker
      gene using lentiviral vectors, the transduced germ cell colonies were visible up
      to 6 mo and displayed an estimated transduction efficiency of 11.1%. These
      results can be applied and extended to isolate and enrich gonocytes of other
      species for in vitro and in vivo studies and to assist in genetic modification of
      male germline stem cells of livestock species.

PMID- 20147733
TI  - The bone marrow-derived human mesenchymal stem cell: potential progenitor of the
      endometrial stromal fibroblast.
AB  - The cellular sources that contribute to the renewal of human endometrium are
      largely unknown. It has been suggested that endometrial stem cells originate from
      bone marrow-derived mesenchymal stem cells (MSC), with subsequent development
      into endometrial stromal fibroblasts (hESF). We hypothesized that if bone marrow
      derived MSC contribute to endometrial regeneration and are progenitors of hESF,
      their treatment with agents known to regulate hESF differentiation could promote
      their differentiation down the stromal fibroblast lineage. To this end, we
      treated bone marrow-derived MSC with estradiol and progesterone, bone
      morphogenetic protein 2 (BMP2), and activators of the protein kinase A (PKA)
      pathway and investigated specific markers of hESF differentiation
      (decidualization). Furthermore, we investigated the transcriptome of these cells
      in response to cAMP and compared this to the transcriptome of hESF decidualized
      in response to activation of the PKA pathway. The data support the idea that MSC
      can be differentiated down the hESF pathway, as evidenced by changes in cell
      shape and common expression of decidual markers and other genes important in hESF
      differentiation and function, and that bone marrow-derived MSC may be a source of
      endometrial stem/progenitor cells. In addition, we identified MSC-specific
      markers that distinguish them from other fibroblasts and, in particular, from
      hESF, which is of biologic relevance and practical value to the field of
      endometrial stem cell research.

PMID- 20147735
TI  - Sexually dimorphic expression of gonadotropin subunits in the pituitary of
      protogynous honeycomb grouper (Epinephelus merra): evidence that follicle
      stimulating hormone (FSH) induces gonadal sex change.
AB  - Recent studies have suggested that the hypothalamic-pituitary-gonadal axis is
      involved in gonadal sex change in sex-changing teleosts. However, its underlying
      mechanism remains largely unknown. In this study, we focused on the distinct
      roles of two gonadotropins (GTHs), follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH), in the protogynous hermaphrodite teleost, honeycomb
      grouper (Epinephelus merra). First, we investigated the expression pattern of
      mRNAs for GTH subunits (cga, fshb, and lhb) in the pituitaries from fish at the
      different sexual phases. Real-time RT-PCR analyses showed that fhsb mRNA levels
      in the female pituitary were low. However, fshb transcripts increased
      dramatically in association with testis development. In contrast, levels of cga
      and lhb mRNAs did not significantly vary during sex change. In addition,
      immunohistochemical observations of Fshb- and Lhb-producing cells in the
      pituitary, through the use of specific antibodies for detections of teleost GTH
      subunits, were consistent with sexually dimorphic expression of Fshb. In order to
      identify the role of GTH in gonad of honeycomb grouper, we treated females with
      bovine FSH (50 or 500 ng/fish) or LH (500 ng/fish) in vivo. After 3 wk, FSH
      treatments induced female-to-male sex change and up-regulated endogenous androgen
      levels and fshb transcripts, whereas LH treatment had no effect on sex change.
      These results suggest that FSH may trigger the female-to-male sex change in
      honeycomb grouper.

PMID- 20147736
TI  - Production of biofunctional recombinant human interleukin 1 receptor antagonist
      (rhIL1RN) from transgenic quail egg white.
AB  - Oviduct-specific expression of heterologous recombinant proteins in transgenic
      birds is a promising technology for the large-scale production of therapeutic
      proteins in eggs. We describe the production of recombinant human interleukin 1
      receptor antagonist (rhIL1RN) in the eggs of transgenic quails. To drive tissue
      specific expression of rhIL1RN, a 1.35-kb fragment of the chicken ovalbumin
      promoter, which contains both the steroid-dependent regulatory element and the
      negative regulatory element, was used. A transgenic quail was generated by
      microinjection of a concentrated stock of lentivirus into stage X blastodermal
      cells. A single copy of the transgene was integrated into the seventh intron of
      the gene for conserved oligomeric golgi complex protein 5 (COG5) on chromosome 1.
      As expected, rhIL1RN expression was restricted to oviductal tissue, and the
      amount of protein deposited in the eggs of homozygous transgenic quails ranged
      from 88.7 to 233.8 ng/ml. Transgene expression was conserved from the G(1)
      generation to the G(4) generation, and there was no evidence of transgene
      silencing. In a bioassay using the EL4.NOB-1/CTLL-2 coculture system, no
      significant difference was observed between the egg-produced rhIL1RN and a
      commercially available rhIL1RN (anakinra).

PMID- 20147737
TI  - WDR20 regulates activity of the USP12 x UAF1 deubiquitinating enzyme complex.
AB  - The UAF1 (Usp1-associated factor 1) protein binds and stimulates three
      deubiquitinating enzymes: USP1, USP12, and USP46. Although the USP1 x UAF1
      complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway,
      less is known about the USP12 x UAF1 and the USP46 x UAF1 complexes. To
      understand further the nature of the USP12 and USP46 complexes, we attempted to
      identify proteins that interact with the USP12 and USP46 deubiquitinating enzyme
      complexes. We identified WDR20, a WD40-repeat containing protein, as a common
      binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20
      associates exclusively with USP12 and USP46, not with USP1. Furthermore, we
      demonstrate the purification of a ternary USP12 x UAF1 x WDR20 complex.
      Interestingly, and consistent with the binding assays, WDR20 stimulated the
      enzymatic activity of USP12 x UAF1, but not of USP1 x UAF1. Consistent with our
      previous report that USP12 and USP46 do not regulate the FA pathway, small
      interference RNA-mediated depletion of WDR20 protein did not affect the FA
      pathway or DNA damage responses. We provide a model in which WDR20 serves as a
      stimulatory subunit for preserving and regulating the activity of the subset of
      the UAF1 x USP complexes.

PMID- 20147738
TI  - Intestine-specific expression of acyl CoA:diacylglycerol acyltransferase 1
      reverses resistance to diet-induced hepatic steatosis and obesity in Dgat1-/-
      mice.
AB  - Mice deficient in acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme
      in triacylglycerol (TG) biosynthesis, are resistant to high-fat (HF) diet-induced
      hepatic steatosis and obesity. DGAT1-deficient (Dgat1-/-) mice have no defect in
      quantitative absorption of dietary fat; however, they have abnormally high levels
      of TG stored in the cytoplasm of enterocytes, and they have a reduced
      postprandial triglyceridemic response. We generated mice expressing DGAT1 only in
      the intestine (Dgat1IntONLY) to determine whether this phenotype contributes to
      resistance to HF diet-induced hepatic steatosis and obesity in Dgat1-/- mice.
      Despite lacking DGAT1 in liver and adipose tissue, we found that Dgat1IntONLY
      mice are not resistant to HF diet-induced hepatic steatosis or obesity. The
      results presented demonstrate that intestinal DGAT1 stimulates dietary fat
      secretion out of enterocytes and that altering this cellular function alters the
      fate of dietary fat in specific tissues.

PMID- 20147739
TI  - Changes in mobility among older adults with psychometrically defined mild
      cognitive impairment.
AB  - Studies have found that adults with possible mild cognitive impairment (MCI)
      exhibit decrements in everyday functioning (e.g., Wadley, V. G., Crowe, M.,
      Marsiske, M., Cook, S. E., Unverzagt, F. W., Rosenberg, A. L., et al. (2007).
      Changes in everyday function among individuals with psychometrically defined mild
      cognitive impairment. Journal of the American Geriatrics Society, 55, 1192-1198).
      However, it is not known whether driving mobility and life space mobility are
      reduced in such individuals. The current study examined 5-year trajectories of
      mobility change in older adults (N = 2,355) with psychometrically defined MCI
      from the Advanced Cognitive Training for Independent and Vital Elderly trial.
      Mixed effect models evaluated group differences for the following mobility
      outcomes: driving space, life space, driving frequency, and driving difficulty.
      Relative to cognitively normal participants, participants with possible MCI
      showed reduced baseline mobility for all outcomes as well as faster rates of
      decline for driving frequency and difficulty. These results suggest that mobility
      declines could be features of MCI, and changes in mobility may be particularly
      important for researchers and clinicians to monitor in this population.

PMID- 20147740
TI  - Management of neuropathic cancer pain.

PMID- 20147741
TI  - Efficacy and safety of ipilimumab monotherapy in patients with pretreated
      advanced melanoma: a multicenter single-arm phase II study.
AB  - BACKGROUND: This phase II study evaluated the safety and activity of ipilimumab,
      a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with
      advanced melanoma. PATIENTS AND METHODS: Patients with previously treated,
      unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3
      weeks for four cycles (induction) followed by maintenance therapy every 3 months.
      The primary end point was best overall response rate (BORR) using modified World
      Health Organization (WHO) criteria. We also carried out an exploratory analysis
      of proposed immune-related response criteria (irRC). RESULTS: BORR was 5.8% with
      a disease control rate (DCR) of 27% (N = 155). One- and 2-year survival rates
      (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%),
      respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43
      patients with disease progression by modified WHO criteria, 12 had disease
      control by irRC (8% of all treated patients), resulting in a total DCR of 35%.
      Adverse events (AEs) were largely immune related, occurring mainly in the skin
      and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs
      were manageable and generally reversible with corticosteroids. CONCLUSION:
      Ipilimumab demonstrated clinical activity with encouraging long-term survival in
      a previously treated advanced melanoma population.

PMID- 20147743
TI  - FGFR4 Arg388 genotype is associated with pathological complete response to
      neoadjuvant chemotherapy for primary breast cancer.
AB  - BACKGROUND: A single-nucleotide polymorphism (SNP) in the FGFR4 gene is
      associated with poor prognosis in solid tumors. A recent study presented the
      first evidence that FGFR4 Arg388 could predict resistance to adjuvant
      chemotherapy in breast cancer. The present study evaluates the potential of this
      SNP to predict response to neoadjuvant chemotherapy (NCT) for primary breast
      cancer (PBC). METHODS: As part of a randomized phase II trial, 257 patients
      received either doxorubicin-cyclophosphamide (AC) or doxorubicin-pemetrexed (AP)
      followed by docetaxel (Doc; Taxotere) as NCT for T2-4/N0-2/M0 PBC. FGFR4 genotype
      analyzed on germline DNA was correlated with clinicopathologic variables,
      clinical response, and pathological complete response (pCR) using univariate and
      multivariate analyses. RESULTS: Only axillary lymph node status was associated
      with FGFR4 Arg388 [odds ratio (OR) 1.82, P = 0.03]. Joint analysis of both
      treatment arms revealed a correlation of FGFR4 Arg388 with clinical response (OR
      2.14, P = 0.03) but not with pCR. In the AC-Doc arm, however, FGFR4 Arg388 was a
      strong predictor of pCR in the multivariate analysis (OR 3.79, P = 0.03). A
      significant interaction between FGFR4 genotype and treatment (P = 0.01) was
      found, indicating a therapy-specific effect. CONCLUSION: We provide the evidence
      that FGFR4 388Arg is an independent predictor of pCR following AC-Doc as NCT in
      PBC.

PMID- 20147742
TI  - All circulating EpCAM+CK+CD45- objects predict overall survival in castration
      resistant prostate cancer.
AB  - BACKGROUND: Presence of five or more circulating tumor cells (CTC) in patients
      with metastatic carcinomas is associated with poor survival. Although many
      objects positive for epithelial cell adhesion molecules and cytokeratin
      (EpCAM+CK+) are not counted as CTC, they may be an important predictor for
      survival. We evaluated the association between these objects and survival in
      patients with prostate cancer. PATIENTS AND METHODS: Included in this follow-up
      study were 179 patients with castration-resistant prostate cancer. CellSearch was
      used to isolate EpCAM+ objects and to stain DNA, cytokeratin and CD45. All
      EpCAM+CK+ objects were subdivided into seven classes on the basis of predefined
      morphological appearance in 63 independent samples. Association of each class
      with survival was studied using Kaplan-Meier and Cox regression analyses.
      RESULTS: Each EpCAM+CK+CD45- class showed a strong association with overall
      survival (P < 0.001). This included small tumor microparticles (S-TMP), which did
      not require a nucleus and thus are unable to metastasize. A higher number of
      objects in any class was associated with decreased survival. A good prediction
      model included large tumor cell fragments (L-TCF), age, hemoglobin and lactate
      dehydrogenase. Models with S-TMP or CTC instead of L-TCF performed similarly.
      CONCLUSION: EpCAM+CK+CD45- that do not meet strict definitions for CTC are strong
      prognostic markers for survival.

PMID- 20147744
TI  - FDG-PET in the assessment of patients with follicular lymphoma treated by
      ibritumomab tiuxetan Y 90: multicentric study.
AB  - BACKGROUND: The aim of this study is the 2-[fluorine-18]fluoro-2-deoxy-D-glucose
      (FDG)-positron emission tomography (PET) evaluation following radioimmunotherapy
      (RIT) with ibritumomab tiuxetan Y 90 in patients with non-Hodgkin's follicular
      lymphoma (FL). MATERIALS AND METHODS: We retrospectively analyzed data from 59
      relapsed or refractory FL patients treated with ibritumomab tiuxetan Y 90 in four
      different PET centers who had a PET scan carried out before and after RIT.
      Possible predictive factors of progression-free survival (PFS) were studied
      through univariate and multivariate analysis. RESULTS: The post-RIT PET
      documented 45.8% complete responders (CR), 25.4% partial responders (PR) and
      28.8% nonresponders [stable disease + progressive disease], with an overall
      survival of 71.2% (range 59.5%-90.9%). With a median follow-up period of 23
      months, the univariate analysis documented a statistically significant relation
      between disease extent before RIT and response to treatment with respect to PFS
      (P = 0.015), while all the other prognostic factors showed no significant
      correlation. When carrying out the multivariate analysis, post-RIT PET resulted
      as the lonely independent predictor of PFS (P < 0.00001). CONCLUSIONS: RIT is an
      effective therapy in FL patients, as confirmed in our study too. Disease
      extension before treatment and response to RIT, as assessed by FDG-PET, result as
      main predictors of PFS, with the post-RIT PET result being the only independent
      predictive factor.

PMID- 20147746
TI  - Chemical inducers of autophagy that enhance the clearance of mutant proteins in
      neurodegenerative diseases.
AB  - Many of the neurodegenerative diseases that afflict people are caused by
      intracytoplasmic aggregate-prone proteins. These include Parkinson disease,
      tauopathies, and polyglutamine expansion diseases such as Huntington disease. In
      Mendelian forms of these diseases, the mutations generally confer toxic novel
      functions on the relevant proteins. Thus, one potential strategy for dealing with
      these mutant proteins is to enhance their degradation. This can be achieved by up
      regulating macroautophagy, which we will henceforth call autophagy. In this
      minireview, we will consider the reasons why autophagy up-regulation may be a
      powerful strategy for these diseases. In addition, we will consider some of the
      drugs and associated signaling pathways that can be used to induce autophagy with
      these therapeutic aims in mind.

PMID- 20147747
TI  - Beyond the canonical 20 amino acids: expanding the genetic lexicon.
AB  - The ability to genetically encode unnatural amino acids beyond the common 20 has
      allowed unprecedented control over the chemical structures of recombinantly
      expressed proteins. Orthogonal aminoacyl-tRNA synthetase/tRNA pairs have been
      used together with nonsense, rare, or 4-bp codons to incorporate >50 unnatural
      amino acids into proteins in Escherichia coli, Saccharomyces cerevisiae, Pichia
      pastoris, and mammalian cell lines. This has allowed the expression of proteins
      containing amino acids with novel side chains, including fluorophores, post
      translational modifications, metal ion chelators, photocaged and photocross
      linking moieties, uniquely reactive functional groups, and NMR, IR, and x-ray
      crystallographic probes.

PMID- 20147748
TI  - Transcriptional switches: chemical approaches to gene regulation.
AB  - Given the role of transcriptional misregulation in the pathogenesis of human
      disease, there is enormous interest in the development of molecules that
      exogenously control transcription in a defined manner. The past decade has seen
      many exciting advancements in the identification of molecules that mimic or
      inhibit the interactions between natural transcriptional activators and their
      binding partners. In this minireview, we focus on four activator.target protein
      complexes, highlighting recent advances as well as challenges in the field.

PMID- 20147749
TI  - Chemical approaches for studying histone modifications.
AB  - Histones form the protein core around which genomic DNA is wrapped in eukaryotic
      chromatin. Numerous genetic studies have established that the structure and
      transcriptional state of chromatin are closely related to histone post
      translational modifications. Further elucidation of the precise mechanistic roles
      for individual histone modifications requires the ability to isolate and study
      homogeneously modified histones. However, the highly heterogeneous nature of
      histone modifications in vivo poses a significant challenge for such studies.
      Chemical tools that have enabled biochemical and biophysical studies of site
      specifically modified histones are the focus of this minireview.

PMID- 20147751
TI  - Chemical inducers of targeted protein degradation.
AB  - The functions of many cellular proteins have been elucidated by selective gene
      inactivation and subsequent phenotypic analysis. For example, genetic mutations,
      gene knock-out generation, and the use of RNA interference to target mRNA for
      degradation can all result in decreased production of a specific protein,
      yielding informative cellular phenotypes. However, these techniques each have
      certain inherent limitations. This minireview focuses on the recent development
      of new approaches to study protein function at the post-translational level,
      namely chemical induction of targeted protein degradation.

PMID- 20147750
TI  - Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case
      study.
AB  - Genome sequencing projects have uncovered thousands of uncharacterized enzymes in
      eukaryotic and prokaryotic organisms. Deciphering the physiological functions of
      enzymes requires tools to profile and perturb their activities in native
      biological systems. Activity-based protein profiling has emerged as a powerful
      chemoproteomic strategy to achieve these objectives through the use of chemical
      probes that target large swaths of enzymes that share active-site features. Here,
      we review activity-based protein profiling and its implementation to annotate the
      enzymatic proteome, with particular attention given to probes that target serine
      hydrolases, a diverse superfamily of enzymes replete with many uncharacterized
      members.

PMID- 20147752
TI  - The influences of impact interface, muscle activity, and knee angle on impact
      forces and tibial and femoral accelerations occurring after external impacts.
AB  - The purpose of this study was to quantify relative contributions of impact
      interface, muscle activity, and knee angle to the magnitudes of tibial and
      femoral accelerations occurring after external impacts. Impacts were initiated
      with a pneumatically driven impacter under the heels of four volunteers. Impact
      forces were quantified with a force sensor. Segmental accelerations were measured
      with bone mounted accelerometers. Experimental interventions were hard and soft
      shock interfaces, different knee angles (0 degrees, 20 degrees, 40 degrees knee
      flexion), and muscular preactivation (0%, 30%, 60% of maximal voluntary
      contraction) of gastrocnemii, hamstrings, and quadriceps. Greater knee flexion
      led to lower impact forces and higher tibial accelerations. Increased muscular
      activation led to higher forces and lower tibial accelerations. The softer of the
      two shock interfaces under study reduced both parameters. The effects on
      accelerations and forces through the activation and knee angle changes were
      greater than the effect of interface variations. The hardness of the two shock
      interfaces explained less than 10% of the variance of accelerations and impact
      forces, whereas knee angle changes explained 25-29%, and preactivation changes
      explained 35-48% of the variances. It can be concluded that muscle force and knee
      joint angle have greater effects in comparison with interface hardness on the
      severity of shocks on the lower leg.

PMID- 20147753
TI  - Stiffness and endurance of a locking compression plate fixed on fractured femur.
AB  - The effects of locking screw position (long column fixation--long distance
      between the nearest screws to the fracture--and short column fixation--short
      distance between the nearest screws to the fracture) and fracture gap size (1-mm
      and 8-mm transverse fracture gap) on stiffness and fatigue of fractured femur
      fixed with a locking compression plate (LCP) were biomechanically evaluated. The
      stiffness of 1-mm fracture gap models and that of intact femoral model were in
      the range of 270-284 N/mm, while those of 8-mm fracture gap models were
      significantly lower (155-170 N/mm). After 1,000,000 cycles of loading, no
      fracture of LCP of 1-mm fracture gap models fixed in either long column or short
      column fashions occurred. On the other hand, the complete fractures of LCPs of 8
      mm fracture gap models fixed in long column and short column fashions occurred
      after 51,500 and 42,000 cycles of loading, respectively. These results suggest
      that the full weight loading may be allowed for the patient with 1-mm transverse
      femoral fracture fixed with an LCP. On the other hand, the full load of walking
      should be avoided for the patient with 8-mm transverse femoral fracture fixed
      with an LCP before adequate healing.

PMID- 20147754
TI  - Gait dynamics on a cross-slope walking surface.
AB  - The purpose of this study was to determine the effect of cross-slope on gait
      dynamics. Ten young adult males walked barefoot along an inclinable walkway.
      Ground reaction forces (GRFs), lower-limb joint kinematics, global pelvis
      orientation, functional leg-length, and joint reaction moments (JRMs) were
      measured. Statistical analyses revealed differences across limbs (up-slope [US]
      and down-slope [DS]) and inclinations (level; 0 degrees; and cross-sloped, 6
      degrees). Adaptations included increases of nearly 300% in mediolateral GRFs (p <
      .001), functional shortening the US-limb and elongation of the DS-limb (p <
      .001), reduced step width (p = .024), asymmetrical changes in sagittal kinematics
      and JRM, and numerous pronounced coronal plane differences including increased US
      hip adduction (and adductor moment) and decreased DS-hip adduction (and adductor
      moment). Data suggests that modest cross-slopes can induce substantial
      asymmetrical changes in gait dynamics and may represent a physical obstacle to
      populations with restricted mobility.

PMID- 20147755
TI  - Influence of the volume and density functions within geometric models for
      estimating trunk inertial parameters.
AB  - The geometric method combines a volume and a density function to estimate body
      segment parameters and has the best opportunity for developing the most accurate
      models. In the trunk, there are many different tissues that greatly differ in
      density (e.g., bone versus lung). Thus, the density function for the trunk must
      be particularly sensitive to capture this diversity, such that accurate inertial
      estimates are possible. Three different models were used to test this hypothesis
      by estimating trunk inertial parameters of 25 female and 24 male college-aged
      participants. The outcome of this study indicates that the inertial estimates for
      the upper and lower trunk are most sensitive to the volume function and not very
      sensitive to the density function. Although it appears that the uniform density
      function has a greater influence on inertial estimates in the lower trunk region
      than in the upper trunk region, this is likely due to the (overestimated) density
      value used. When geometric models are used to estimate body segment parameters,
      care must be taken in choosing a model that can accurately estimate segment
      volumes. Researchers wanting to develop accurate geometric models should focus on
      the volume function, especially in unique populations (e.g., pregnant or obese
      individuals).

PMID- 20147756
TI  - Mechanical energy expenditures and movement efficiency in full body reaching
      movements.
AB  - The effect of target location, speed, and handedness on the average total
      mechanical energy and movement efficiency is studied in 15 healthy subjects (7
      males and 8 females with age 22.9 +/- 1.79 years old) performing full body
      reaching movements. The average total mechanical energy is measured as the time
      average of integration of joint power, potential energy, and kinetic energy
      respectively. Movement efficiency is calculated as the ratio of total kinetic
      energy to the total joint power and potential energy. Results show that speed and
      target location have significant effects on total mechanical energy and movement
      efficiency, but reaching hand only effects kinetic energy. From our findings we
      conclude that (1) efficiency in whole body reaching is dependent on whether the
      height of the body center of mass is raised or lowered during the task; (2)
      efficiency is increased as movement speed is increased, in part because of
      greater changes in potential energy; and (3) the CNS does not appear to use
      movement efficiency as a primary planning variable in full body reaching. It may
      be dependent on a combination of other factors or constraints.

PMID- 20147757
TI  - The force-length curves of the human rectus femoris and gastrocnemius muscles in
      vivo.
AB  - For a physiologically realistic joint range of motion and therefore range of
      muscle fiber lengths, only part of the whole muscle force-length curve can be
      used in vivo; that is, only a section of the force-length curve is expressed.
      Previous work has determined that the expressed section of the force-length curve
      for individual muscles can vary between subjects; however, the degree of
      intersubject variability is different for different muscles. This study
      determined the expressed section of both the rectus femoris and gastrocnemius-
      muscles with very different ratios of tendon slack length to muscle fiber optimum
      length--for 28 nonspecifically trained subjects to test the hypothesis that the
      value of this ratio affects the amount of variability in the expressed section.
      The force-length curves of the two muscles were reconstructed from moment-angle
      data using the method of Herzog & ter Keurs (1988). There was no relationship
      between the expressed sections of the force-length curve for the two muscles.
      Less variability was found in the expressed section of the gastrocnemius compared
      with the rectus femoris, supporting the hypothesis. The lack of relationship
      between the expressed sections of the two muscles has implications for motor
      control and for training muscle for rehabilitation.

PMID- 20147758
TI  - Three-dimensional trunk kinematics and low back pain in elite female fast
      bowlers.
AB  - This study aimed to investigate the bowling techniques of female fast bowlers and
      identify any association between a history of low back pain (LBP) and the
      movement patterns of the thorax relative to the pelvis during the delivery stride
      of the bowling action. Three-dimensional kinematic data were collected from 26
      elite Australian female fast bowlers using an eight-camera Vicon motion analysis
      system. Nineteen bowlers used a mixed action, 6 bowlers used a semiopen action,
      and 1 bowler used a side-on action. Fourteen bowlers had a history of LBP. Eight
      of these 14 bowlers used a mixed action, and bowlers with more shoulder
      counterrotation were no more likely to have a history of LBP. Bowlers with a
      history of LBP positioned the thorax in more left lateral flexion relative to the
      pelvis between 73-79% of the delivery stride, and moved the thorax through a
      significantly greater range of lateral flexion relative to the pelvis during the
      delivery stride compared with bowlers with no history of LBP. This information
      will give coaches and support staff a better understanding of female bowling
      technique and may facilitate better screening practices for elite female
      cricketers.

PMID- 20147759
TI  - A combined muscle model and wavelet approach to interpreting the surface EMG
      signals from maximal dynamic knee extensions.
AB  - This study aimed to identify areas of reduced surface EMG amplitude and changed
      frequency across the phase space of a maximal dynamic knee extension task. The
      hypotheses were that (1) amplitude would be lower for eccentric contractions
      compared with concentric contractions and unaffected by fiber length and (2) mean
      frequency would also be lower for eccentric contractions and unaffected by fiber
      length. Joint torque and EMG signals from the vasti and rectus femoris were
      recorded for eight athletic subjects performing maximum knee extensions at 13
      preset crank velocities spanning +/-300 degrees x s(-1). The instantaneous
      amplitude and mean frequency were calculated using the continuous wavelet
      transform time-frequency method, and the fiber dynamics were determined using a
      muscle model of the knee extensions. The results indicated that (1) only for the
      rectus femoris were amplitudes significantly lower for eccentric contractions (p=
      .019) and, for the vasti, amplitudes during eccentric contractions were less than
      maximal but this was also the case for concentric contractions due to a
      significant reduction in amplitude toward knee extension (p= .023), and (2) mean
      frequency increased significantly with decreasing fiber length for all knee
      extensors and contraction velocities (p= .029). Using time-frequency processing
      of the EMG signals and a muscle model allowed the simultaneous assessment of
      fiber length, velocity, and EMG.

PMID- 20147760
TI  - Biomechanics of off-center monoarticular exercises with lever selectorized
      equipment.
AB  - We have developed a 2-D analytical biomechanical model for monoarticular open
      kinetic-chain exercises with lever selectorized equipment, and different relative
      placement between the joint center of rotation (J) and the center of rotation (C)
      of the resistance input lever ("off-center" exercises). All the relevant
      geometrical aspects of such exercises have been characterized: the change with
      the joint angle of the distance between the resistance pad (P) and J, and of the
      angle between CP and JP (i.e., the angle between the resistance input lever and
      the exercising limb). These changes may strongly affect the joint load and the
      muscle torque in inverse dynamic problems, given the joint kinematics and the
      mass of the selected weight stack. Therefore, the muscle torque, the shear and
      axial components of the joint load have been calculated analytically as a
      function of the relative positioning of C and J, and the length CP, in addition
      to the parameters that define the joint kinematics, the equipment mechanics, and
      the external load. From these results we have derived the optimal cam profiles
      for "off-center" exercises, as well as the geometrical "off-center" setting that
      minimizes the shear component of the tibiofemoral joint load in leg extension
      equipment.

PMID- 20147761
TI  - Swimming propulsion forces are enhanced by a small finger spread.
AB  - The main aim of this study was to investigate the effect of finger spread on the
      propulsive force production in swimming using computational fluid dynamics.
      Computer tomography scans of an Olympic swimmer hand were conducted. This
      procedure involved three models of the hand with differing finger spreads:
      fingers closed together (no spread), fingers with a small (0.32 cm) spread, and
      fingers with large (0.64 cm) spread. Steady-state computational fluid dynamics
      analyses were performed using the Fluent code. The measured forces on the hand
      models were decomposed into drag and lift coefficients. For hand models, angles
      of attack of 0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75
      degrees, and 90 degrees, with a sweep back angle of 0 degrees, were used for the
      calculations. The results showed that the model with a small spread between
      fingers presented higher values of drag coefficient than did the models with
      fingers closed and fingers with a large spread. One can note that the drag
      coefficient presented the highest values for an attack angle of 90 degrees in the
      three hand models. The lift coefficient resembled a sinusoidal curve across the
      attack angle. The values for the lift coefficient presented few differences among
      the three models, for a given attack angle. These results suggested that fingers
      slightly spread could allow the hand to create more propulsive force during
      swimming.

PMID- 20147762
TI  - Mathematical functions and their properties as relevant to the biomechanical
      modeling of cell and tissue damage.
AB  - The extrapolation of biological damage from a biomechanical model requires that a
      closed-form mathematical damage threshold function (DTF) be included in the
      model. A DTF typically includes a generic load variable, being the critical load
      (e.g., pressure, strain, temperature) causing irreversible tissue or cell damage,
      and a generic time variable, which represents the exposure to the load (e.g.,
      duration, strain rate). Despite the central role that DTFs play in biomechanical
      studies, there is no coherent literature on how to formulate a DTF, excluding the
      field of heat-induced damage studies. This technical note describes six
      mathematical function types (Richards, Boltzmann, Morgan-Mercer-Flodin, Gompertz,
      Weibull, Bertalanffy) that are suitable for formulating a wide range of DTFs.
      These functions were adapted from the theory of restricted growth, and were
      fitted herein to describe biomechanical damage phenomena. Relevant properties of
      each adapted function type were extracted to allow efficient fitting of its
      parameters to empirical biomechanical data, and some practical examples are
      provided.

PMID- 20147763
TI  - Accuracy of 3-D reconstruction with occlusions.
AB  - A marker has to be seen by at least two cameras for its three-dimensional (3-D)
      reconstruction, and the accuracy can be improved with more cameras. However, a
      change in the set of cameras used in the reconstruction can alter the kinematics.
      The purpose of this study was to quantify the harmful effect of occlusions on two
      dimensional (2-D) images and to make recommendations about the signal processing.
      A reference kinematics data set was collected for a three degree-of-freedom
      linkage with three cameras of a commercial motion analysis system without any
      occlusion on the 2-D images. In the 2-D images, some occlusions were artificially
      created based on trials of real cyclic motions. An interpolation of 2-D
      trajectories before the 3-D reconstruction and two filters (Savitsky-Golay and
      Butterworth filters) after reconstruction were successively applied to minimize
      the effect of the 2-D occlusions. The filter parameters were optimized by
      minimizing the root mean square error between the reference and the filtered
      data. The optimal parameters of the filters were marker dependent, whereas no
      filter was necessary after a 2-D interpolation. As the occlusions cause
      systematic error in the 3-D reconstruction, the interpolation of the 2-D
      trajectories is more appropriate than filtering the 3-D trajectories.

PMID- 20147764
TI  - Relative phase coordination analysis in the assessment of dynamic gait symmetry.
AB  - A variety of kinematic and kinetic measures are typically used to examine gait
      symmetry. Here we make the argument that gait asymmetries may be most clearly
      revealed through higher-order coordinative measures such as continuous relative
      phase (CRP). Participants walked on a treadmill with a load attached to their
      nondominant limb. Gait symmetry was then assessed using spatial (angular),
      temporal (velocity), and higher-order (CRP) symmetry measures. It was found that
      higher-order measures were most sensitive at assessing asymmetries due to load
      manipulation at both the distal and proximal segments. Symmetry measures derived
      from velocity variables were more sensitive than angular measures at detecting
      asymmetries, but were less sensitive compared with CRP. Asymmetries were also
      more readily detected using segmental angles compared with joint angles. These
      results suggest that gait asymmetries that emerge from changing constraints
      manifest along both spatial and temporal dimensions.

PMID- 20147765
TI  - A novel dynamic ankle-supinating device.
AB  - Lateral ankle sprains (LAS) are among the most common joint injuries, and
      although most are resolved with conservative treatment, others develop chronic
      ankle instability (AI). Considerable attention has been directed toward
      understanding the underlying causes of this pathology; however, little is known
      concerning the neuromuscular mechanisms behind AI. A biomechanical analysis of
      the landing phase of a drop jump onto a device that simulates the mechanism of a
      LAS may give insight into the dynamic restraint mechanisms of the ankle by
      individuals with AI. Furthermore, work evaluating subjects who have a history of
      at least one lateral ankle sprain, yet did not develop AI, may help elucidate
      compensatory mechanisms following a LAS event. Identifying proper neuromuscular
      control strategies is crucial in reducing the incidence of AI.

PMID- 20147766
TI  - Physical activity and walking onset in infants with Down syndrome.
AB  - Infants with Down syndrome (DS) are described as being less active and they also
      experience significant delays in motor development. It is hypothesized that early
      infant physical activity may be influential for the acquisition of independent
      walking. Physical activity was monitored longitudinally in 30 infants with DS
      starting at an average age of 10 months participating in a treadmill training
      intervention. Actiwatches were placed on infants' trunk and right ankle for a 24
      hr period, every other month until walking onset. Data were analyzed to separate
      sedentary-to-light activity (low-act) and moderate-to-vigorous activity (high
      act). Results showed that more leg high-act at an average age of 12 and 14 months
      is related to earlier onset of walking. It is recommended that early leg activity
      should be promoted in infants with DS.

PMID- 20147767
TI  - The Emotional Reactions to Challenging Behavior Scale-Korean (ERCBS-K):
      modification and validation.
AB  - The purpose of this study was to explore the original version of Mitchell and
      Hastings's (1998) Emotional Reaction to Challenging Behavior Scale (ERCBS) and
      estimate validity and reliability of a revised version containing 29 items. The
      Emotional Reaction to Challenging Behavior Scale-Korean (ERCBS-K) was studied
      using 445 in-service physical educators (228 females; 217 males). Data were
      collected using onsite administration as well as mail survey administration
      procedures. Confirmatory and exploratory factor analyses results supported a five
      factor, 28-item scale ERCBS-K. Acceptable internal consistency coefficients were
      found for each of the subscales of the ERCBS-K (Cronbach's alpha ranged from 0.71
      to 0.87).

PMID- 20147768
TI  - Short term auditory pacing changes dual motor task coordination in children with
      and without dyslexia.
AB  - This study examined the effect of short-term auditory pacing practice on dual
      motor task performance in children with and without dyslexia. Groups included
      dyslexic with Movement Assessment Battery for Children (MABC) scores > 15th
      percentile (D_HIGH, n = 18; mean age 9.89 +/- 2.0 years), dyslexic with MABC < or
      = 15th percentile (D_LOW, n = 15; mean age 10.43 +/- 1.8 years), and typically
      developing (TD, n = 18; mean age 10.64 +/- 1.8 years). Participants clapped and
      walked simultaneously for 3 pretest trials, completed 16 trials with auditory
      pacing, and 3 posttest trials without pacing. D_LOW differed significantly from
      D_HIGH and TD in mean relative phase (MRP) of the clap relative to the step, and
      variability (VRP) of the MRP. Significant differences also existed between
      pretest blocks and all other blocks in MRP. The results suggest that a short-term
      auditory pacing may be effective in improving MRP in all children. Further, there
      may be subtypes of dyslexia wherein children have more profound coordination
      difficulties and may preferentially change dual motor task performance with
      auditory pacing.

PMID- 20147769
TI  - Nutritional practices of competitive British wheelchair games players.
AB  - This study described the dietary intake profiles of 14 female (F) and 9 male (M)
      trained British wheelchair games players. The M group showed significantly higher
      daily energy (2060 +/- 904 vs. 1520 +/- 342 kcal x day(-1)), carbohydrate and
      protein intakes than the F group (p < .05). The energy derived from carbohydrate,
      protein, and fat for both F and M groups were similar (53.6%, 16.9% and 29.3% and
      53.3%, 19.0% and 26.8%, respectively), yet the carbohydrate intakes were slightly
      lower than those recommended for athletes. Only two participants from the F group
      showed adequate intakes of iron, and 19 participants from both F and M groups did
      not meet the dietary fiber recommendation but this may be related to
      individualized bowel management strategies. Overall, the dietary practices
      encompassed aspects of the dietary guidelines recommended for sport, but
      balancing the energy needs of wheelchair games play with the promotion of long
      term health still needs careful consideration.

PMID- 20147770
TI  - The effects of whole body vibration on bone mineral density for a person with a
      spinal cord injury: a case study.
AB  - Bone mineral density (BMD) loss is a medical concern for individuals with spinal
      cord injury (SCI). Concerns related to osteoporosis have lead researchers to use
      various interventions to address BMD loss within this population. Whole body
      vibration (WBV) has been reported to improve BMD for postmenopausal women and
      suggested for SCI. The purpose of this case study was to identify the effects of
      WBV on BMD for an individual with SCI. There were three progressive phases
      (standing only, partial standing, and combined stand with vibration), each
      lasting 10 weeks. Using the least significant change calculation, significant
      positive changes in BMD were reported at the trunk (0.46 g/cm(2)) and spine (.093
      g/cm(2)) for phase 3 only. Increases in leg lean tissue mass and reduction in
      total body fat were noted in all three phases.

PMID- 20147771
TI  - Normal distribution of palpebral fissure lengths in Canadian school age children.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS) includes the facial dysmorphic feature
      of short palpebral fissures (PFs) and short PFs are a key physical marker for
      identifying children with FAS and some other rarer conditions. There is concern
      that normative data on PFs now available may not reflect all racial/ethnic groups
      and might be inaccurate in general. OBJECTIVES: To accomplish a large population
      based study that would accurately determine normative PF values across the full
      diversity of the Canadian school age population. METHODS: A normative sample of
      school age children was identified in Vancouver, British Columbia and Winnipeg,
      Manitoba to reflect the diversity of racial and national groups in Canada. The
      sample included students in grades 2, 4, 6, 8, and 10 from 17 schools in
      Vancouver and 31 schools in Winnipeg. Schools were selected based on racial
      diversity obtained from data from the 2001 Statistics Canada census. 1064
      students in Vancouver and 1033 students in Winnipeg were photographed in a
      standardized way. Photographs were analyzed using a computerized method. RESULTS:
      Analysis demonstrated that PFs do grow with age and there is a slight but
      meaningful difference between boys and girls in each age group. It is possible to
      define Canadian standards without reference to racial or ethnic origin.
      CONCLUSION: Mean results with norms and standard deviations are presented in
      figures for clinical use and are clinically smaller than those found in the most
      commonly used reference book.

PMID- 20147772
TI  - An evaluation of pharmacist and health food store retailer's knowledge regarding
      potential drug interactions associated with St. John's wort.
AB  - BACKGROUND: Natural health products (NHP) are increasingly being used by patients
      concomitantly receiving prescription drugs, which can result in potentially
      serious drug-herb interactions. This is particularly true for St. John's wort.
      OBJECTIVE: This study was conducted to evaluate pharmacists and natural health
      product retailers' knowledge on this topic. METHODS: An interviewer approached 24
      pharmacists and 6 natural health product retailers to obtain information
      regarding St. John's wort. If asked, the interviewer indicated that they were
      currently using cyclosporine to treat a problem of proteinuria. The response of
      the pharmacist or NHP retailer to a series of questions was recorded after the
      encounter. RESULTS: 90% of respondents indicated that St. John's wort was useful
      for treating depression. Two-thirds of the respondents required prompting by the
      interviewer before providing any comments pertaining to safety. 60% of the
      respondents inquired about concurrent medications and 40% made statements
      regarding potential drug-herb interactions. CONCLUSION: Despite the potential for
      a serious drug-herb interaction involving St. John's wort and cyclosporine, less
      than half of the pharmacists and natural health product retailers that were
      encountered in the study addressed this topic with the prospective
      patient/client. Individuals selling natural health products need to communicate
      more information to their patients/clients regarding potential drug-herb
      interactions.

PMID- 20147773
TI  - Acute intravascular haemolysis associated with intravenous administration of
      meropenem in a sixty four year old man.
AB  - We present the first reported case of severe intravascular haemolysis associated
      with the use of meropenem in a 64 year old man. The report highlights a further
      possible drug related cause of intravascular haemolysis. The patient, who had a
      background of dialysis dependent renal failure, epilepsy and learning
      difficulties, was admitted to the intensive care unit following laparotomy and
      large bowel resection. His background also included a reported childhood allergy
      to penicillin. Along with initial haemodynamic and ventilatory support he was
      treated with cefuroxime, metronidazole and gentamicin without incident. He went
      on to develop an abdominal collection, for which treatment included meropenem.
      Associated with the administration of meropenem was the development of severe
      intravascular haemolysis confirmed by laboratory analysis and microscopy, which
      resolved on cessation of meropenem therapy. We discuss the possible mechanisms
      involved in the development of drug induced haemolysis and suggest the most
      likely cause in this case.

PMID- 20147774
TI  - Automatic quantification of the Poincare plot asymmetry of NN-interval
      recordings.
AB  - We investigated the electrocardiographic substrate underlying the asymmetry of
      Poincare plots of NN intervals (NNI) on different time scales and conceived a
      method for automatic asymmetry quantification (AQUA), which is based on the
      observation that left-sided comet asymmetry (A(L)) is due to sudden increases
      (SIC), and right-sided comet asymmetry (A(R)) to sudden decreases (SDC) of cycle
      lengths, and that both the SIC and SDC episodes were consistently associated with
      significant changes in P-wave magnitude and/or polarity indicating a shift in
      dominant pacemaker activity. The performance of AQUA was validated in 15
      endurance trained athletes (age: 29 +/- 6 years) exhibiting marked comet
      asymmetry, and 11 untrained controls (age: 40 +/- 15 years) with symmetrical
      comet patterns. SICs were reliably identified by AQUA with a sensitivity of 0.950
      and a specificity of 0.985, and SDCs with a sensitivity of 0.952 and a
      specificity of 0.965. In the athletes, the magnitude of SICs exceeded that of
      SDCs significantly, and the occurrence of SICs and SDCs was closely correlated
      with periods of increased efferent vagal activity. It is concluded that AQUA is a
      useful tool for the identification and quantification of specific aspects of
      nonlinear heart rate dynamics manifesting as Poincare plot asymmetries.

PMID- 20147775
TI  - Comparison of respiratory-induced variations in photoplethysmographic signals.
AB  - Photoplethysmography (PPG) is an optical method for detecting blood volume
      changes in tissue. Respiratory-induced intensity, frequency and amplitude
      variations are contained in the PPG signal; thus, an understanding of the
      relationships between all of these variations and respiration is essential to
      advancing respiration monitoring based on PPG. This study investigated
      correlations between respiratory-induced variations extracted from PPG and
      simultaneous respiratory signals. PPG signals were recorded from 28 healthy
      subjects under eight different conditions. Six respiratory-induced variations,
      i.e. the period of the systole, diastole and pulse, the amplitude of the systole
      and diastole, and the intensity variation, were determined from the PPG signal.
      The results indicate that, compared with the period of the pulse, the period of
      the systole and diastole correlates weakly with respiration; the amplitude of the
      diastole has a stronger correlation with respiration than the amplitude of the
      systole. For men, when the respiratory rate is less than 10 breaths min(-1), the
      period of the pulse has the strongest correlation with respiration, whereas up to
      or above 15 breaths min(-1), the intensity variation becomes strongest in the
      sitting posture, while the amplitude of the diastole is strongest in the supine
      posture. For women, compared with the other variations, the period of the pulse
      has nearly the strongest correlation with respiration, independent of respiratory
      rate or posture.

PMID- 20147776
TI  - Resonant activation: a strategy against bacterial persistence.
AB  - A bacterial colony may develop a small number of cells genetically identical to,
      but phenotypically different from, other normally growing bacteria. These so
      called persister cells keep themselves in a dormant state and thus are
      insensitive to antibiotic treatment, resulting in serious problems of drug
      resistance. In this paper, we proposed a novel strategy to 'kill' persister cells
      by triggering them to switch, in a fast and synchronized way, into normally
      growing cells that are susceptible to antibiotics. The strategy is based on
      resonant activation (RA), a well-studied phenomenon in physics where the internal
      noise of a system can constructively facilitate fast and synchronized barrier
      crossings. Through stochastic Gilliespie simulation with a generic toggle switch
      model, we demonstrated that RA exists in the phenotypic switching of a single
      bacterium. Further, by coupling single cell level and population level
      simulations, we showed that with RA, one can greatly reduce the time and total
      amount of antibiotics needed to sterilize a bacterial population. We suggest that
      resonant activation is a general phenomenon in phenotypic transition, and can
      find other applications such as cancer therapy.

PMID- 20147777
TI  - On the electrical intestine turbulence induced by temperature changes.
AB  - Paralytic ileus is a temporary syndrome with impairment of peristalsis and no
      passage of food through the intestine. Although improvements in supportive
      measures have been achieved, no therapy useful to specifically reduce or
      eliminate the motility disorder underlying postoperative ileus has been developed
      yet. In this paper, we draw a plausible, physiologically fine-tuned scenario,
      which explains a possible cause of paralytic ileus. To this aim we extend the
      existing 1D intestinal electrophysiological Aliev-Richards-Wikswo ionic model
      based on a double-layered structure in two and three dimensions. Thermal coupling
      is introduced here to study the influence of temperature gradients on intestine
      tissue which is an important external factor during surgery. Numerical
      simulations present electrical spiral waves similar to those experimentally
      observed already in the heart, brain and many other excitable tissues. This fact
      seems to suggest that such peculiar patterns, here electrically and thermally
      induced, may play an important role in clinically experienced disorders of the
      intestine, then requiring future experimental analyses in the search for possible
      implications for medical and physiological practice and bioengineering.

PMID- 20147778
TI  - Robust transport by multiple motors with nonlinear force-velocity relations and
      stochastic load sharing.
AB  - Transport by processive molecular motors plays an important role in many cell
      biological phenomena. In many cases, motors work together to transport cargos in
      the cell, so it is important to understand the mechanics of the multiple motors.
      Based on earlier modeling efforts, here we study effects of nonlinear force
      velocity relations and stochastic load sharing on multiple motor transport. We
      find that when two or three motors transport the cargo, then the nonlinear and
      stochastic effects compensate so that the mechanical properties of the transport
      are robust. Similarly, the transport is insensitive to compliance of the cargo
      motor links. Furthermore, the rate of movement against moderate loads is not
      improved by increasing the small number of motors. When the motor number is
      greater than 4, correlations between the motors become negligible, and the
      earlier analytical mean-field theory of the multiple motor transport holds. We
      predict that the effective diffusion of the cargo driven by the multiple motors
      under load increases by an order of magnitude compared to that for the single
      motor. Finally, our simulations predict that the stochastic effects are
      responsible for a significant dispersion of velocities generated by the 'tug-of
      war' of the multiple opposing motors.

PMID- 20147779
TI  - The role of chemokine receptor CXCR4 in lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung
      cancer (SCLC), which comprises 15% of all lung cancers, is almost exclusively due
      to smoking and is highly aggressive due to early widespread metastasis. While
      combination chemotherapy has lead to modest improvements in outcome, the five
      year overall survival for SCLC remains at 5%. Identifying distinct biochemical
      pathways of metastasis and chemotherapy resistance in SCLC may lead to novel
      therapeutic approaches and improve survival in SCLC patients. The chemokine
      receptor CXCR4 is emerging as an important target in cancer growth, metastasis,
      relapse and resistance to therapy. In this article, we review the structure and
      function of CXCR4 and its ligand, CXCL12, as well as mechanisms of CXCR4/CXCL12
      signal transduction in lung cancer. We review the current preclinical and
      translational research involving this pathway in lung cancer and the clinical
      development of several novel agents targeting the CXCR4/CXCL12 pathway. Further
      understanding of the CXCR4/CXCL12 pathway in SCLC and NSCLC may provide a
      rationale for innovative research on the CXCR4 receptor as a potential novel
      therapeutic target in lung cancer.

PMID- 20147782
TI  - Current world literature.

PMID- 20147780
TI  - Identification of miRNAs that are associated with tumor metastasis in
      neuroblastoma.
AB  - The discovery of microRNAs (miRNAs) has opened a new avenue for both diagnosis
      and treatment of cancers. Accumulating experimental evidences indicate that
      miRNAs are aberrantly expressed in different tumor types and have a critical role
      in tumorigenesis. However, the miRNA expression profile in neuroblastoma (NB),
      one of the most common cancer forms in children, has not been well characterized.
      In the present study, we established a heterotopic transplant mice model of NB
      and employed miRNA microarray analysis to identify miRNAs that are differentially
      expressed in metastatic NB compared to primary NB. A list of 54 miRNAs was found
      to be significantly altered in metastatic tumors compared to primary tumors.
      These differentially-expressed miRNAs were selectively validated by a stem-loop
      qRT-PCR assay. Furthermore, we predicted a list of potential miRNA-target pairs
      that may be involved in the metastasis of neuroblastoma by three different
      computer-aided algorithms. Taken together, our results indicate that a unique
      panel of miRNAs are associated with metastatic NB and these differentially
      expressed miRNAs may play an important role in the NB metastatic process. This
      finding may also shed light in our understanding of the nature of metastatic NB
      and provide a potential novel target for therapeutic treatment of this tumor.

PMID- 20147784
TI  - Can a decisional algorithm be used in first-line treatment of advanced nonsmall
      cell lung cancer?

PMID- 20147785
TI  - Editorial overview: transplantation.

PMID- 20147786
TI  - Current world literature.

PMID- 20147787
TI  - The Livermore phantom history and supplementation.
AB  - In vivo monitoring facilities determine the absence or presence of internally
      entrained radionuclides. To be of greatest utility, the detection systems must
      detect and quantify the nuclides of interest at levels of interest. Phantoms have
      been developed to improve measurements at in vivo monitoring facilities. Since
      the 1970's, the torso phantom originally developed at Lawrence Livermore National
      Laboratory (LLNL, or simply "Livermore") continues to be a well-used tool at lung
      monitoring facilities, especially for the detection of low-energy photons from
      transuranics. The history of its development from need through design development
      and current availability is summarized. The authors have taken the LLNL phantom
      one step further by scanning the phantom surface and announce the availability of
      the scan files on the Internet.

PMID- 20147788
TI  - Employee exposure to (222)Rn and (220)Rn in three fish culture stations in
      Pennsylvania.
AB  - Employee exposures to Rn and Rn were measured in three Commonwealth fish
      hatcheries using specially designed personal dosimeters to determine whether
      remediation might be necessary. Employees utilizing the hatch house would wear
      the dosimeter and keep track of their time in the hatch house. Area detectors
      were also deployed full time in each hatch house. Exposure measurements were
      compared to U.S. Nuclear Regulatory Commission, U.S. Environmental Protection
      Agency, and Occupational Safety and Health Administration exposure limits. All
      measured employee exposures to Rn and Rn were very low and well below currently
      established regulatory limits. However, hatch house radon concentrations are
      significantly elevated above the U.S. Environmental Protection Agency residential
      guideline of 148 Bq m.

PMID- 20147789
TI  - Evaluation of Cuprimine and Syprine for decorporation of (60)Co and (210)Po.
AB  - The acknowledged risk of deliberate release of radionuclides into local
      environments by terrorist activities has prompted a drive to improve novel
      materials and methods for removing internally deposited radionuclides. These
      decorporation treatments will also benefit workers in the nuclear industry,
      should an exposure occur. Cuprimine and Syprine are oral therapeutics based on
      the active ingredients D-penicillamine and N,N'-bis-(2-aminoethyl)-1,2
      ethanediamine dihydrochloride, respectively. These therapeutic drugs have been
      used for several decades to treat Wilson's disease, a genetic defect leading to
      copper overload, by chelation and accelerated excretion of internally deposited
      copper. Studies were undertaken to evaluate these FDA-approved drugs for the in
      vivo decorporation of radioactive cobalt (Co) and polonium (Po) using male Wistar
      Han rats. In these studies, Co or Po was administered to animals by IV injection,
      followed by oral gavage doses of either Cuprimine or Syprine. Control animals
      received the radionuclide alone. For Co studies, animals received a single dose
      of Cuprimine or Syprine, while for Po studies animals were repeatedly dosed at 24
      h intervals for a total of 5 doses. Results show that Syprine significantly
      increased urinary elimination and skeletal concentrations of Co compared to
      controls. While Cuprimine had little effect on total excretion of Co, the
      skeletal, kidney, liver, muscle, and stomach tissues had significantly lower
      radioactivity compared to control animals. The low overall excretion of Po made
      it difficult to reliably measure urinary or fecal radioactivity and draw a
      definitive conclusion on the effect of Cuprimine or Syprine treatment on
      excretion. However, Cuprimine treatment was effective at reducing spleen levels
      of Po compared to controls. Similarly, Syprine treatment produced statistically
      significant reductions of Po in the spleen and skeletal tissues compared to
      control animals. Based on these promising findings, further studies to evaluate
      the dose-response pharmacokinetic profiles for decorporation are warranted.

PMID- 20147790
TI  - Characterization of the world's first nuclear explosion, the Trinity test, as a
      source of public radiation exposure.
AB  - The world's first atomic bomb was tested in New Mexico on 16 July 1945. From 1999
      through 2008, scientists working for the Centers for Disease Control and
      Prevention gathered information relevant to past releases from Los Alamos
      activities, including the Trinity test. Detonation on a 30.5 m tower enhanced
      radioactive fallout, and terrain and wind patterns caused "hot spots" of
      deposition. Several ranchers reported that fallout resembling flour was visible
      for 4 to 5 d after the blast, and residents living as close as 19 km from ground
      zero collected rain water from metal roofs for drinking. Pressures to maintain
      secrecy and avoid legal claims led to decisions that would not likely have been
      made in later tests. Residents were not warned before the test or informed
      afterward about potential protective actions, and no evacuations were conducted.
      Occupied homes were overlooked on the day of the blast. Exposure rates in
      residential areas were recorded as high as 1.4 microC kg s (20 R h) using
      instruments that were crude, ill suited to field use, and incapable of
      effectively measuring alpha contamination from about 4.8 kg of unfissioned
      plutonium that was dispersed. Vehicle shielding and contamination were recognized
      but not corrected for. To date, the post-shot field team measurements have not
      been rigorously evaluated, cross-checked, adjusted, or subjected to uncertainty
      analysis. Evaluations of Trinity fallout published to date have not addressed
      internal doses to members of the public following intakes of contaminated air,
      water, or foods. The closing of these data gaps appears feasible with the
      information that has been assembled and would support placement of the Trinity
      event in perspective as a source of public radiation exposure and more defensible
      evaluation of the potential for human health effects.

PMID- 20147791
TI  - Nationwide surveys of chest, abdomen, lumbosacral spine radiography, and upper
      gastrointestinal fluoroscopy: a summary of findings.
AB  - This paper reports findings from Nationwide Evaluation of X-ray Trends surveys
      conducted in 2001, 2002, and 2003 of clinical facilities that perform routine
      radiographic examinations of the adult chest, abdomen, lumbosacral spine, and
      upper gastrointestinal fluoroscopic examinations. Randomly identified clinical
      facilities were surveyed in approximately 40 participating states. For the
      surveyed radiographic exams, additional facilities that use computed radiography
      or digital radiography were surveyed to ensure adequate sample sizes for
      determining comparative statistics. State radiation control personnel performed
      site visits and collected data on patient exposure, radiographic/fluoroscopic
      technique factors, image quality, and quality-control and quality-assurance
      practices. Results of the NEXT surveys are compared with those of previous
      surveys conducted in 1964 and 1970 by the U.S. Public Health Service and the Food
      and Drug Administration. An estimated 155 million routine adult chest exams were
      performed in 2001. Average patient entrance skin air kerma from chest radiography
      at facilities using digital-based imaging modalities was found to be
      significantly higher (p < 0.001), but not so for routine abdomen or lumbosacral
      spine radiography. Digital-based imaging showed a substantial reduction in
      patient exposure for the radiographic portion of the routine upper
      gastrointestinal fluoroscopy exam. Long-term trends in surveyed diagnostic
      examinations show that average patient exposures are at their lowest levels. Of
      concern is the observation that a substantial fraction of surveyed non-hospital
      sites indicated they do not regularly have a medical physics survey conducted on
      their radiographic equipment. These facilities are likely unaware of the
      radiation doses they administer to their patients.

PMID- 20147792
TI  - Concerning the health effects of internally deposited radionuclides.
AB  - The ionizing radiation dose-response relationships for internally deposited
      radionuclides are examined using data from humans involving Ra and laboratory
      animal studies involving alpha-emitters Ra, Ra, Ra, Th, Pu, Pu, and Am and beta
      emitters Y, Sr, Y, and Ce. Intake routes included ingestion, inhalation, and
      injection. The lifetime effects are best described by three-dimensional average
      dose-rate/time/response surfaces that compete with other causes of death during
      an individual's lifetime. Using maximum likelihood survival regression methods,
      the characteristic logarithmic slope for cancer induction was found to be about
      negative one-third for alpha-emitters or about negative two-thirds for beta
      emitters. At the higher average dose-rates the principal deleterious effects were
      those associated with radiation-induced injury while at intermediate average dose
      rates radiation-induced cancer predominates. The relative biological
      effectiveness for cancer induction of high linear energy transfer alpha radiation
      with respect to low linear energy transfer beta radiation is a strong function of
      dose-rate. As average dose-rate decreases, the effectiveness of the beta
      irradiation drops off more rapidly than that of the alpha irradiation. The
      cumulative dose yielding a specific level of induced cancer risk is less at lower
      dose-rates than at higher dose-rates showing an apparent inverse dose-rate effect
      (up to a factor of about 10 for high linear energy transfer alpha radiation and a
      factor of about 2 for low linear energy transfer beta radiation). The cumulative
      radiation dose is neither an accurate nor an appropriate measure of cancer risk
      associated with protracted ionizing radiation exposure. Cancer risk associated
      with protracted ionizing radiation exposure is a non-linear function of lifetime
      average dose-rate to the affected tissues. At low average dose-rates the long
      latency time required for radiation-induced cancer may exceed the natural
      lifespan. This long latency results in a lifespan virtual threshold (cancer risk
      p < 0.001) for each internally deposited radionuclide. For young adult beagles,
      bone sarcoma induction from alpha-emitting radionuclides was unlikely for
      cumulative doses below about 1 Gy (20 Sv) delivered specifically to the sensitive
      tissues at bone surfaces in a manner associated with radionuclide relative
      potency from highest for Th, Pu, and Pu to lowest for Ra. Bone sarcoma induction
      from ingested Sr was unlikely for cumulative beta radiation doses below about 20
      Gy (20 Sv), but beta irradiation of tissues adjacent to bone also induced
      leukemia and soft tissue carcinomas above 10 Gy (10 Sv). Inhaled radionuclides
      tended to be most potent in producing lung carcinoma when the radiation dose was
      most uniformly distributed in the lung. In young adult beagles lung carcinoma
      from inhaled alpha-emitting Pu in the dispersible nitrate form was unlikely for
      cumulative doses below about 0.5 Gy (10 Sv) and below higher cumulative doses for
      other forms of Pu and Pu depending on relative potency. Lung carcinoma from
      inhaled beta-emitting Y in relatively insoluble fused aluminosilicate particles
      was unlikely for cumulative doses below about 5 Gy (5 Sv) and below higher doses
      for inhaled particles with Y, Ce, or Sr in order of decreasing potency.

PMID- 20147793
TI  - Detection of (154)Eu in patients post (153)Sm-EDTMP therapy using a clinical
      gamma camera.
AB  - Enhancements in radiation detection equipment at border crossings and airports
      resulted in a report to our institution from a Sm-EDTMP therapy patient who was
      questioned after triggering radiation alarms. Using a clinical SPECT camera in
      its service mode, gamma-ray spectroscopy was performed on three patients whose Sm
      EDTMP injections were given between 4 mo and 2 y prior to this study. The spectra
      revealed the presence of high-energy photon peaks characteristic of those from
      Eu. While the presence of Eu in Sm injections is documented in the literature,
      the implications of its presence are not widely known. The results of this study
      show that Eu (t1/2 = 8.5 y) remains in the bones in detectable amounts for
      several years and may create concerning situations for post therapy patients at
      some security checkpoints. Institutions performing Sm-EDTMP therapy may want to
      inform their patients of this situation and provide a wallet card.

PMID- 20147794
TI  - Tools for creating and manipulating voxel phantoms.
AB  - The National Internal Radiation Assessment Section's Human Monitoring Laboratory
      (HML) has purchased and developed a number of in-house tools to create and edit
      voxel phantoms. This paper describes the methodology developed in the HML using
      those tools to prepare input files for Monte Carlo simulations using voxel
      phantoms. Three examples are given. The in-house tools described in this paper,
      and the phantoms that have been created using them, are all publically available
      upon request from the corresponding author.

PMID- 20147798
TI  - Transitions of care: what is the role that home care plays?

PMID- 20147799
TI  - Keeping safety a priority in home care and hospice: one agency's journey.
AB  - Implementing senior leadership Safety Rounds at one home care and hospice
      organization has strengthened the safety culture and improved communication at
      all levels. Safety Rounds have led to identification of safety and quality
      priorities and enabled leaders to act proactively rather than reactively, by
      identifying safety risks and concerns before an error occurs or a patient is
      harmed.

PMID- 20147800
TI  - Causes of unplanned hospital admissions: implications for practice and policy.
AB  - Unplanned hospitalizations among home health patients were reviewed to identify
      preventable hospital admissions and their causes. Study methods included
      treatment record review; interviews with home health visit staff, supervisors,
      and managers; and review of orientation materials and policies. Findings from
      this study suggest focus areas for home health agencies and other stakeholders to
      reduce acute care hospitalization rates and in other quality improvement
      initiatives.

PMID- 20147801
TI  - Intimate partner violence in older women: what home healthcare clinicians should
      know.
AB  - Older women can be victims of intimate partner violence (IPV), and home
      healthcare clinicians should know what they can do. Although there is no
      instrument specific to screening for IPV in older women within the home
      environment, home healthcare clinicians can use currently available resources and
      lobby for better resources to screen for and serve older women who may be victims
      of IPV. Forensic nursing education can provide additional skills to identify
      possible victims of violence, gather evidence, document findings, and provide
      treatment and referrals.

PMID- 20147803
TI  - The PHQ-2 on OASIS-C: a new resource for identifying geriatric depression among
      home health patients.
AB  - Since Medicare first implemented the home care Outcome and Assessment Information
      Set (OASIS) in 1999, we have learned a great deal about depression among the
      homebound elderly. First, we know that major depression is a highly prevalent
      illness in home care. With depression rates at almost 15%, home care-along with
      nursing homes-has among the highest rates of any healthcare setting.

PMID- 20147805
TI  - Performance improvement in managed long-term care: physician communication in
      managing community-dwelling older adults.
AB  - This performance improvement initiative focused on the nurse consultant's
      communication with the physician about care management of community-dwelling
      older adults. Three defined areas were measured: (1) changes in clinical setting,
      (2) reporting adverse effects from medications that can contribute to falls, and
      (3) HbA1c results >9. Physicians were informed of our quality initiative; nurse
      practitioners led workshops addressing barriers to effective communication; and
      portable reference cards were created to assist staff in organizing information
      prior to contacting a physician. The Project Goal of 10% improvement for all
      three indicators was achieved. Staff identified best practices for communicating
      with physicians.

PMID- 20147806
TI  - Factors influencing the health-related lifestyle of community-dwelling older
      adults.

PMID- 20147807
TI  - Rekindle your passion for the nursing profession and home healthcare and hospice
      specialty.

PMID- 20147809
TI  - Sipping through a straw.

PMID- 20147810
TI  - Guided bone regeneration using nonexpanded polytetrafluoroethylene membranes in
      preparation for dental implant placements--a report of 420 cases.
AB  - The biologic principle of guided bone regeneration has been successfully used to
      prevent bone loss in extraction sites. This study comprises 420 cases of alveolar
      ridge maintenance in preparation for dental implant placements. Nonexpanded
      polytetrafluoroethylene membranes were positioned over all extraction sites and
      left intentionally exposed. Lyophilized mineralized bone allografts were used to
      prevent membrane collapse when buccal bone walls were lost. Membranes were
      removed at week 4. At the time of implant placements, all sites presented soft
      tissue compatibility with keratinized gingiva. The mucogingival junction position
      seemed to be preserved. Exposed nonexpanded polytetrafluoroethylene membranes
      associated, or not, with bone graft provide tissue formation suitable for implant
      placement.

PMID- 20147811
TI  - Screw- versus cement-retained implant restorations: current concepts.
AB  - The debate between screw- versus cement-retained implant prostheses has long been
      discussed but the best type of implant prosthesis remains controversial among
      practitioners. An understanding of their properties will help the clinician in
      selecting the ideal prosthesis for each clinical case while promoting final
      esthetic outcomes. With the evolving technology and knowledge, an update of the
      current trends is necessary. This article provides an overview of the different
      characteristics of screw- and cement-retained implant restorations, and how they
      may influence the esthetics, retrievability, retention, passivity, occlusion,
      accessibility, cost, and provisional restorations. Problems and complications
      frequently encountered are discussed and treatment solutions are proposed.

PMID- 20147812
TI  - Migrated maxillary implant removed via semilunar hiatus by transnasal endoscope.
AB  - Endoscopic surgery via nasal approach to remove the implant body from the
      semilunar hiatus is presented with the images of the computed tomography and the
      intraoperative endoscopic findings.

PMID- 20147813
TI  - Placement of implant after bone graft using J block allograft.
AB  - Securing sufficient alveolar bone is important for a successful implant. Alveolar
      bone should be augmented to adequate height and width for an implant to satisfy
      the functional, biological, and aesthetic properties. The subjects of this study
      were 3 patients with severe bone defects caused by either a periodontal disease
      or a failure of implants on mandibular posterior tooth, mandibular anterior
      tooth, and maxillary posterior tooth. The shape of the commercial block allograft
      (Puros J-Block, Zimmer Dental Inc., Carlsbad, CA) was modified to match the shape
      of the defect, and resorbable membrane (Puros Pericardium Allograft Membrane,
      Tutogen Medical GmbH, Germany) was used before suturing the soft tissue. The
      transplant sites were exposed 4 months later to install the implant. The grafted
      bone was united with the bone tissue to obtain enough alveolar ridge and to
      install the implants. Bone allograft used in these cases reduced the need to
      collect autogenous bone in patients with severe alveolar ridge loss.

PMID- 20147815
TI  - Finite element analysis of 2 immediate loading systems in edentulous mandible:
      rigid and semirigid splinting of implants.
AB  - PURPOSE: The objective of this study was to evaluate the stress on the cortical
      bone around single body dental implants supporting mandibular complete fixed
      denture with rigid (Neopronto System-Neodent) or semirigid splinting system
      (Barra Distal System-Neodent). METHODS AND MATERIALS: Stress levels on several
      system components were analyzed through finite element analysis. Focusing on
      stress concentration at cortical bone around single body dental implants
      supporting mandibular complete fixed dentures with rigid (Neopronto System
      Neodent) or semirigid splinting system (Barra Distal System-Neodent), after axial
      and oblique occlusal loading simulation, applied in the last cantilever element.
      RESULTS: The results showed that semirigid implant splinting generated lower von
      Mises stress in the cortical bone under axial loading. Rigid implant splinting
      generated higher von Mises stress in the cortical bone under oblique loading.
      CONCLUSION: It was concluded that the use of a semirigid system for
      rehabilitation of edentulous mandibles by means of immediate implant-supported
      fixed complete denture is recommended, because it reduces stress concentration in
      the cortical bone. As a consequence, bone level is better preserved, and implant
      survival is improved. Nevertheless, for both situations the cortical bone
      integrity was protected, because the maximum stress level findings were lower
      than those pointed in the literature as being harmful. The maximum stress limit
      for cortical bone (167 MPa) represents the threshold between plastic and elastic
      state for a given material. Because any force is applied to an object, and there
      is no deformation, we can conclude that the elastic threshold was not surpassed,
      keeping its structural integrity. If the force is higher than the plastic
      threshold, the object will suffer permanent deformation. In cortical bone, this
      represents the beginning of bone resorption and/or remodeling processes, which,
      according to our simulated loading, would not occur.

PMID- 20147814
TI  - CTX biochemical marker of bone metabolism. Is it a reliable predictor of
      bisphosphonate-associated osteonecrosis of the jaws after surgery? Part II: a
      prospective clinical study.
AB  - Biochemical markers of bone metabolism have been used in medicine to evaluate and
      provide treatment to patients with metabolic bone diseases, such as osteoporosis.
      Serum cross-linked C-telopeptide of type I collagen (CTX) is a marker of
      osteoclast activity and is used to assess the level of bone resorption. Recently,
      in oral and maxillofacial surgery, it was proposed that the levels of serum CTX
      may predict the subsequent risk of developing osteonecrosis of the jaws (ONJ)
      after oral surgery procedures for patients taking oral bisphosphonates (BPs). The
      goal of this study was to determine whether this specific serum marker of bone
      resorption could preoperatively predict the risk of developing ONJ from oral
      BPs.We hypothesized that there is no clinical correlation between the observed
      preoperative serum CTX values and the risk of developing ONJ. The authors examine
      the scientific basis (validity) of the morning fasting serum CTX test in 163
      consecutive patients who underwent various oral surgery procedures in the office.
      The authors also review the laboratory test results and the recommended protocol
      based on the test values. One hundred sixty-three patients (mean age, 75.9 years)
      were divided into 2 groups. Group I was the control group that consisted of 109
      patients taking oral BPs who did not take the CTX test preoperatively. Group 2
      consisted of 54 patients taking BPs and who elected to have the CTX test
      performed to assess their level of risk of developing ONJ, preoperatively. Both
      groups of patients were observed for a period of 8 weeks for signs and symptoms
      of BP-associated ONJ after surgery. The clinical data at 8 weeks and beyond
      revealed that there was no evidence of BP-associated ONJ in all participants. We
      conclude that the serum CTX is not a valid preoperative test to accurately assess
      the level of risk of developing ONJ and is not indicated in the oral surgery
      patient.

PMID- 20147816
TI  - Evaluation of rotational freedom of In-Ceram ceramic blank abutments before and
      after infiltration.
AB  - PURPOSE: Laboratory processing of implant-supported prostheses may alter the
      surface of the abutment in contact with the corresponding surface and thus the
      interface fit. This study assessed changes in the rotational freedom (R) at the
      interface of 1 implant ceramic abutments before and after preparation and glass
      infiltration processes. MATERIALS AND METHODS: The abutment R was assessed for 20
      as-received In-Ceram Ceramic Blanks over synOcta abutments and after both
      preparation and infiltration procedures. RESULTS: Compared with the as-received
      blanks, there was a statistically significant (P < 0.009) increase of 0.8 minutes
      in the R after preparation and glass infiltration processes. CONCLUSION: The
      results of this investigation suggest that, if all laboratory steps are observed
      carefully, changes at the abutment interface of Ceramic Blanks do not occur.

PMID- 20147817
TI  - Smoking, diabetes mellitus, periodontitis, and supportive periodontal treatment
      as factors associated with dental implant survival: a long-term retrospective
      evaluation of patients followed for up to 10 years.
AB  - OBJECTIVES: To evaluate the factors associated with long-term implant survival in
      a large cohort of patients in regular follow-up until data collection. METHODS:
      The study population consisted of 475 patients who were referred to a private
      clinic limited to Periodontics and Implantology between November 1995 and July
      2006. Data were collected from patient files with regards to smoking habits,
      periodontal condition, diabetes mellitus, implant survival, and time when implant
      failure occurred. Patients were divided into those who participated in a
      supportive periodontal program in the clinic and those who only attended the
      annual free-of-charge implant examination. RESULTS: A total of 1626 implants were
      placed with a follow-up ranging from 1 to 114 months (average 30.82 +/- 28.26
      months). Overall, 77 (4.7%) implants were lost in 58 (12.2%) patients after a
      mean period of 24.71 +/- 25.84 months. More than one-half of the patients (246;
      51.7%) participated in a structured supportive periodontal program in the clinic,
      and 229 (48.3%) only attended to the annual free-of-charge implant examination.
      Smoking and attendance in a regular supportive periodontal program were
      statistically associated with implant survival. Patients with (treated) moderate
      to-advanced chronic periodontal disease demonstrated higher implant failure rates
      but, this difference did not reach statistical significance. Diabetes mellitus
      was not related to implant survival in this patient cohort. CONCLUSIONS: Smoking
      and attendance in a regular supportive periodontal program were found to be
      strongly related to implant survival. Special attention should be given to
      continuous periodontal supportive programs to implant patients.

PMID- 20147818
TI  - Implant restoration of partially edentulous ridges: a review of 121 Nigerian
      patients.
AB  - OBJECTIVE: Because of increasing health awareness, many Nigerian patients are
      demanding that their lost tooth/teeth be replaced with dental implants. This
      study reports the pattern and distribution of implant replacement of lost
      tooth/teeth in a private dental practice in Lagos, Nigeria. METHODS: A
      retrospective review of implant replacement of lost tooth/teeth over a period of
      6 years at Schubbs Private Dental Clinic, Lagos, was carried out. Data analysis
      included age, sex, occupation, habits and medical condition of patients,
      augmentation procedure, technique of implant placement (immediate vs conventional
      loading) tooth/teeth replaced, and follow-up period. RESULTS: A total of 227
      implants (Bicon, Boston, MA) with complete superstructure were placed in 121
      patients(males = 68, females = 53; age range: 15-74 years). Majority of the
      patients were of high socioeconomic class. Ten (8.3%) patients had immediate
      implants and 111 (91.7%) undergone 2-stage implant procedures. The highest number
      (39.2%) of implants was placed in the molar region, and the replacement of the
      canines was the lowest (3.1%). Success rate over a period of 6 years was 96%. Of
      the 9 (4%) implants that failed, 2 were repeated and remained functional till
      date. CONCLUSIONS: Dental implant therapy as a means of tooth replacement is
      gaining popularity among Nigerian social upper class. Success rate in this series
      is comparable with previous reports from Europe and America.

PMID- 20147819
TI  - Implant survival rates in a condensed surgical and prosthetic training program
      for general practitioners in dental implants.
AB  - PURPOSE: The aim of this study was to evaluate the survival rates for surgical
      placement of dental implants in the Implant Dentistry Study Consortium (IDSC), a
      training program for general dentists in the UAE. MATERIALS: The records of the
      program were reviewed, and all implants placed were evaluated, and the survival
      and failures were identified. These records were compared with those from an
      experienced prosthodontist who has been trained in both the surgical and
      restorative phases of implant dentistry. Descriptive statistics and Kaplan-Meier
      survival curves were calculated. The Kaplan-Meier statistics were compared using
      the log-rank test. RESULTS: The characteristics of the population of the IDSC and
      the prosthodontist were similar. During the study interval, the prosthodontist
      had 299 implants in 145 subjects and IDSC with 217 implants in 104 subjects
      placed. The survival rates were 96% for the experienced prosthodontist and 93.5%
      for IDSC dentists. The Kaplan-Meier curves were not statistically different from
      each other, P > 0.05. CONCLUSION: A closely supervised training program in dental
      implantology of 4 sessions, 3 day each, can provide successful surgical
      experiences for the program participants.

PMID- 20147820
TI  - Success rate of immediate implants placed and restored by novice operators.
AB  - AIMS: The primary aim of this study was to evaluate the 1-year crestal bone loss
      and success rate of an immediately placed single-stage implant placed and
      restored by novice operators. A secondary aim was to determine the patient's
      assessment of the appearance of the final restoration. METHODS: Fifty-one
      patients received a tooth extraction and placement of at least 1 immediate
      implant by a Graduate Periodontics resident. Clinical and radiographic
      measurements were taken at the surgical, 4-month, and 1-year follow-up visits.
      After at least 3 months healing, dental students restored the implants with
      either a crown or an overdenture. Patient satisfaction was assessed using 5
      categories: excellent, very good, good, fair, or poor. RESULTS: Sixty-two
      immediate implants were placed. The success rate was 100% at the 12-month visit
      and was subclassified as grade 3 because of the mean first year bone loss of 1.3
      +/- 1.0 mm. Using the 2008 classification of Misch et al, 42 implants were
      classified as success optimum health, 19 as survival satisfactory health, and 1
      as survival compromised health. Radiographic bone loss was stratified by implant
      platform position relative to the alveolar crest and changed from time 0 to time
      12 by -1.0 +/- 1.2 mm for the supracrestal group (n = 25, P < 0.05), -1.5 +/- 0.9
      mm for the crestal group (n = 31, P < 0.05), and -1.3 +/- 1.2 mm for the
      subcrestal group (n = 6, P < 0.05). The supracrestal group had significantly less
      bone loss than either the crestal or the subcrestal group (P < 0.05). The
      appearance of the final restoration at 1 year was rated excellent by 82% of
      patients, very good by 16%, and good by 2%. CONCLUSIONS: Immediate implant
      placement by novice operators using routine dental school procedures was a highly
      predictable procedure as indicated by the 100% success rate at 12 months. Most
      patients rated the restoration appearance as excellent.

PMID- 20147821
TI  - The safest care possible for childbearing women and their infants.

PMID- 20147822
TI  - Nurses and bias: providing better care with respect and understanding.

PMID- 20147823
TI  - People factors that contribute to patient safety.

PMID- 20147824
TI  - Risk management in intrapartum fetal monitoring: accidental recording of the
      maternal heart rate.

PMID- 20147825
TI  - The hypothalamic-pituitary-adrenal axis during pregnancy.

PMID- 20147826
TI  - Human factors and error in perinatal care: the interplay between nurses,
      machines, and the work environment.
AB  - Perinatal nurses work with intricate systems requiring frequent interface with
      complex technology. This interplay is strongly influenced by the work environment
      and systems operations. The interplay among worker, technology, and the
      environment increases the risk of medical error, adverse patient outcomes, and in
      some instances, healthcare team member injury. Human factors engineering is an
      applied science that provides the study of the interface between people and
      machines. Human factors engineers design operations and systems that recognize
      the capacities and limitations of human beings and make it difficult for errors
      to occur. This article discusses the role of human factors research in healthcare
      design and the application of human factors engineering to perinatal settings.
      Recommendations are offered for the development of ultrasafe, high-reliability
      operations based on knowledge accrued through human factors research.

PMID- 20147827
TI  - Perinatal safety: from concept to nursing practice.
AB  - Communication and teamwork problems are leading causes of documented preventable
      adverse outcomes in perinatal care. An essential component of perinatal safety is
      the organizational culture in which clinicians work. Clinicians' individual and
      collective authority to question the plan of care and take action to change the
      direction of a clinical situation in the patient's best interest can be viewed as
      their "agency for safety." However, collective agency for safety and commitment
      to support nurses in their role of advocacy is missing in many perinatal care
      settings. This article draws from Organizational Accident Theory, High
      Reliability Theory, and Symbolic Interactionism to describe the nurse's role in
      maintaining safety during labor and birth in acute care settings and suggests
      actions for supporting the perinatal nurse at individual, group, and systems
      levels to achieve maximum safety in perinatal care.

PMID- 20147828
TI  - Effective implementation strategies and tactics for leading change on maternity
      units.
AB  - Change implementation within organizations is a complex and dynamic process that
      is not always successful. Tailoring the implementation strategies and tactics to
      address the identified barriers to change is one method that has been shown to be
      effective. Examples of 3 broad types of interrelated strategies used by frontline
      leaders when implementing quality improvement (QI) projects are (1) discourse
      (communication), (2) education (formal and informal), and (3) data (audit).
      Examples of common barriers to implementation are leaders' and clinicians'
      knowledge, attitudes, and practices, the QI topic characteristics, and the
      implementation climate. External pressures from national organizations such as
      the National Quality Forum, the Leapfrog Group, and The Joint Commission likely
      facilitate change. Knowledgeable, tenacious, and creative frontline physician and
      nurse leaders may have the greatest impact on QI implementation effectiveness
      because they are the individuals who decide how the strategies and tactics will
      be tailored.

PMID- 20147829
TI  - Reconsideration of the costs of convenience: quality, operational, and fiscal
      strategies to minimize elective labor induction.
AB  - Elective induction of labor is at an all-time high in the United States despite
      known associated risks. It can lead to birth of an infant too early, a long
      labor, exposure to a high-alert medication with its potential side effects,
      unnecessary cesarean birth, and maternal and neonatal morbidity. There is a
      cascade of interventions related to elective induction such as an intravenous
      line, continuous electronic fetal monitoring, confinement to bed, amniotomy,
      pharmacologic labor stimulating agents, parental pain medications, and regional
      anesthesia, each with their own set of potential complications and risk of
      iatrogenic harm. These risks apply to all women having the procedure, however for
      nulliparous women before 41 weeks of gestation with an unfavorable cervix, the
      main risk is cesarean birth after unsuccessful labor induction with the potential
      for maternal and neonatal morbidity and increased healthcare costs. When cesarean
      occurs, subsequent births are likely to be via cesarean as well. Elective labor
      induction before 41 weeks is inconsistent with quality perinatal care, and
      performance of this unnecessary procedure should be minimized. Convenience as the
      reason for labor induction is contrary to a culture focused on patient safety. A
      review of current evidence, followed by changes in practice, is warranted to
      support the safest care possible during labor and birth. Various strategies to
      reduce the rate of elective induction in the United States are presented.

PMID- 20147831
TI  - Implementing the evidence-based change in perinatal and neonatal nursing.
AB  - Perinatal nursing and neonatal nursing both have a scientific base upon which to
      base care, and great strides have been made in translating research into practice
      in both of these specialties. However, barriers still exist for nurses in
      implementing evidence-based perinatal and neonatal care. Patient, provider, and
      systems factors that influence how evidence is translated into practice are
      discussed. Suggestions for how to implement practice change when evidence is
      inadequate are also discussed. Finally, examples of how the scientific base for
      both perinatal nursing and neonatal nursing can be more efficiently implemented
      are outlined on the basis of the state of implementation science in the United
      States today.

PMID- 20147832
TI  - Assessing environmental readiness: first steps in developing an evidence-based
      practice implementation culture.
AB  - Significant emphasis has been placed on evidence-based practice (EBP) in today's
      healthcare systems. Nurses are expected to practice within an EBP framework by
      using current, reliable, and valid research. However, implementing EBP is not
      always easy and can be challenging. In order for nurses to provide evidence-based
      care, they need to be cognizant of organizational factors that can potentially
      hinder or support an EBP culture. This article provides practitioners with an
      understanding of how to evaluate environmental readiness for implementation of
      EBP within their organization. Barriers and facilitators for implementing EBP at
      the organizational level, at the interdisciplinary team level, and within nursing
      are also described. To successfully implement EBP, it is important to recognize
      the interaction between these 3 levels and to highlight the important role nurses
      play as interdisciplinary team members in supporting an EBP environment.

PMID- 20147834
TI  - Translating the evidence-based NICU COPE program for parents of premature infants
      into clinical practice: impact on nurses' evidence-based practice and lessons
      learned.
AB  - BACKGROUND AND PURPOSE: Many interventions that have been supported as
      efficacious through research never make it to clinical practice to improve care
      and patient outcomes. Therefore, the purposes of this dissemination
      implementation study were to determine (a) the impact of translating the evidence
      based Creating Opportunities for Personal Empowerment (COPE) program for parents
      of premature infants into clinical practice on nurses' EBP (evidence-based
      practice) beliefs and implementation; (b) the best strategy for disseminating
      COPE into the neonatal intensive care unit (NICU), including evaluating the use
      of a COPE EBP mentor; and (c) barriers and facilitators to successful
      implementation of the COPE program. SUBJECTS AND METHODS: The subjects for this
      study were 81 (45%) out of 180 nurses from a 55-bed NICU of a large children's
      hospital located in the Southwest region of the United States. The nurses
      completed the EBP beliefs and EBP implementation scales at baseline and 6 months
      after a full-day workshop on COPE and EBP and introduction of the COPE program
      into the unit. Evaluations from the nurses assisted in the identification of
      barriers and facilitators that fostered implementation of COPE in the NICU.
      FINDINGS AND CONCLUSIONS: Nurses in the 2 pods in which COPE was being
      implemented reported higher EBP beliefs and greater EBP implementation than did
      nurses in the non-COPE pods. The EBP mentor was instrumental in routine delivery
      of COPE to the parents. Strategies to accelerate the translation of efficacious
      interventions into clinical practice and to create cultures to support evidence
      based care in healthcare systems are urgently needed.

PMID- 20147835
TI  - Improving the safety of neonatal care through the development and implementation
      of a staff-focused delta team.
AB  - Patient safety is one of the greatest imperatives in healthcare today, yet there
      are many obstacles that must be overcome to make healthcare delivery truly safe.
      Critically ill newborns are among the most medically fragile patients in
      hospitals today. Given their size and gestational age, the tolerance for error
      within this population is extremely small. Medical errors that may be less
      consequential in adults can be disastrous for infants. Developing a culture of
      safety demands a mind-set that continuously seeks out vulnerabilities and
      prospectively addresses them through systems-based rather than individual-based
      solutions. The complexities of clinical care and intricacies of human behavior
      may prevent total elimination of risk, but caregivers are in a position to
      develop a culture of safety that can minimize risks for adverse events in the
      neonatal intensive care unit. Specific strategies used to successfully implement
      a staff-focused patient safety program are described in this article. These
      strategies include the development of systemwide and unit-based interdisciplinary
      safety teams to proactively identify and address safety concerns, development of
      specific tools and techniques used for analysis and prioritization of risk,
      resources that teams used to support an environment of safety; and implementation
      of staff-driven solutions to address safety concerns.

PMID- 20147836
TI  - In praise of the 3 ps.

PMID- 20147837
TI  - The unique complexity of the CYP3A4 upstream region suggests a nongenetic
      explanation of its expression variability.
AB  - OBJECTIVE: The individually variable and unpredictable expression of CYP3A4
      compromises therapies with 50% of contemporary drugs. Gene variants explain only
      a fraction of this variability. METHODS: We investigated the evolution of CYP3A4
      transcriptional regulation by nuclear receptors such as the xenobiotics sensors
      PXR and CAR. RESULTS: The combination of a proximal ER6 element with XREM and
      CLEM represents the original scheme of CYP3A regulation by nuclear receptors in
      placental mammals. Among human CYP3A genes, this scheme is retained only in
      CYP3A4, whereas non-CYP3A4 genes lost these elements to a variable extent during
      primate evolution. In parallel, the number of elements outside XREM and CLEM
      potentially responsive to PXR and CAR increased in primate CYP3A4 orthologs,
      which led to enhanced CYP3A4 inducibility. Additions to the other primate CYP3A
      genes were more restricted and specific, as exemplified by a CYP3A5 DR4 site
      responsive to CAR, but not to PXR. All these changes resulted in human CYP3A4
      having a much more complex upstream regulatory region in comparison to its
      paralogs. CONCLUSION: Instead of gene variants, the intraindividual CYP3A4
      expression variability in humans may be primarily caused by particular
      sensitivity of this gene to endogenous and exogenous PXR and CAR ligands
      conferred by the unique complexity of its upstream regulatory region.

PMID- 20147838
TI  - Systematic analysis of the antiproliferative effects of novel and standard
      anticancer agents in rhabdoid tumor cell lines.
AB  - Rhabdoid tumors are highly aggressive pediatric malignancies. Although the
      prognosis of children with rhabdoid tumors has improved, it still remains dismal
      and long-term survivors suffer from severe side effects of current therapeutic
      approaches. The objective of our study was to explore the toxicity of standard
      and novel anticancer drugs against rhabdoid tumors in vitro and to prioritize
      them for future preclinical and clinical studies. Antitumor activity of 10
      standard anticancer drugs (doxorubicin, idarubicin, mitoxantrone, actinomycin D,
      temozolomide, carmustine, oxaliplatin, vinorelbine, methotrexate, thiotepa), five
      target-specific drugs (sorafenib, imatinib, roscovitine, rapamycin, ciglitazone)
      and two herbal compounds (curcumin and apigenin) was assessed by a modified 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell
      proliferation assay on three rhabdoid tumor cell lines, A204, G401, and BT16,
      derived from different anatomical sites. Comparable with their high clinical
      activity, anthracyclines inhibited tumor cell proliferation by 50% (GI50) in the
      nanomolar range. Actinomycin D exhibited the lowest GI50 values overall ranging
      from 2.8x10(-6) nmol/l for G401 to 3.8 nmol/l for A204 cells while thiotepa was
      the only alkylating drug that inhibited tumor cell growth in clinically relevant
      concentrations. Target-specific drugs, such as sorafenib, roscovitine, and
      rapamycin, showed promising results as well. In this report, we show for the
      first time that apigenin and curcumin effectively inhibit rhabdoid tumor cell
      growth. Supporting earlier reports we conclude that cyclin D1 seems to be an
      excellent target in the treatment of rhabdoid tumors. Idarubicin or mitoxantrone
      represent potent alternatives to doxorubicin, and vinorelbine may substitute
      vincristine in future clinical trials.

PMID- 20147839
TI  - Nonprogressive congenital cerebellar ataxia, iris heterochromia, mental
      retardation and language impairment in two brothers.

PMID- 20147840
TI  - The risks and benefits of snow sports for people with disabilities: a review of
      the literature.
AB  - Snow sports are popular pastimes with therapeutic potential. The aim of this
      review is to evaluate the risk of injury and evidence of benefits of alpine
      skiing (including sit-skiing), Nordic skiing, and snowboarding for people with
      disabilities. Ten studies met the inclusion criteria from 357 citations. Research
      in this area is still in its infancy, but the risks of engaging in snow sports
      appear no greater than those of the general population, and there is some
      evidence that skiing can positively influence self-esteem, physical self-worth,
      standing balance, and gross motor function among individuals with a disability.

PMID- 20147841
TI  - Specific phenotypic and functional features of natural killer cells from HIV
      infected long-term nonprogressors and HIV controllers.
AB  - BACKGROUND: Recent evidence suggests that natural killer (NK) cells play a
      crucial role in the HIV pathogenesis. Long-term nonprogressor (LTNP) and HIV
      controllers are rare HIV-infected patients who control viral replication and show
      delayed disease progression. They represent fascinating models of natural
      protection against disease progression and for studying the immunological
      response to the virus. METHODS: We have conducted an extensive analysis of the
      phenotypic and functional properties of CD56, CD56 and CD56/CD16 NK cell subsets
      from LTNP and HIV-controllers, and compared them with HIV progressors and healthy
      donors. RESULTS: Hierarchical clustering analysis of NK phenotypic markers
      revealed that LTNP and HIV controllers, exhibit peculiar phenotypic features,
      associated with high levels of interferon-g, activation markers, and cytolytic
      activity in CD3CD56 NK cells against K562 target cells. More importantly,
      cytolytic activity against autologous CD4 T cells is abrogated after treatment
      with anti-NKp44L mAb, in LTNP and HIV progressors, suggesting a key role of
      NKp44L. In contrast, in HIV controllers and healthy donors, NKp44L expression on
      CD4 T cells and autologous NK lysis were both poorly detected. CONCLUSIONS: These
      results show that NK cells from LTNP and HIV controllers display phenotypic and
      functional features and suggest a consistent continuous involvement of the innate
      immune response in the failure to control viral replication. Collectively, these
      data may have important implication in the design of new anti-HIV therapeutical
      strategies based on the particular functional activity of NK cells.

PMID- 20147842
TI  - Thiazolidinediones prevent PDGF-BB-induced CREB depletion in pulmonary artery
      smooth muscle cells by preventing upregulation of casein kinase 2 alpha'
      catalytic subunit.
AB  - BACKGROUND: The transcription factor CREB is diminished in smooth muscle cells
      (SMCs) in remodeled, hypertensive pulmonary arteries (PAs) in animals exposed to
      chronic hypoxia. Forced depletion of cyclic adenosine monophosphate response
      element binding protein (CREB) in PA SMCs stimulates their proliferation and
      migration in vitro. Platelet-derived growth factor (PDGF) produced in the hypoxic
      PA wall promotes CREB proteasomal degradation in SMCs via phosphatidylinositol-3
      kinase/Akt signaling, which promotes phosphorylation of CREB at 2 casein kinase 2
      (CK2) sites. Here we tested whether thiazolidinediones, agents that inhibit
      hypoxia-induced PA remodeling, attenuate SMC CREB loss. METHODS: Depletion of
      CREB and changes in casein kinase 2 catalytic subunit expression and activity
      were measured in PA SMC treated with PDGF. PA remodeling and changes in medial PA
      CREB and casein kinase 2 levels were evaluated in lung sections from rats exposed
      to hypoxia for 21 days. RESULTS: We found that the thiazolidinedione
      rosiglitazone prevented PA remodeling and SMC CREB loss in rats exposed to
      chronic hypoxia. Likewise, the thiazolidinedione troglitazone blocked PA SMC
      proliferation and CREB depletion induced by PDGF in vitro. Thiazolidinediones did
      not repress Akt activation by hypoxia in vivo or by PDGF in vitro. However, PDGF
      induced CK2 alpha' catalytic subunit expression and activity in PA SMCs, and
      depletion of CK2 alpha' subunit prevented PDGF-stimulated CREB loss. Troglitazone
      inhibited PDGF-induced CK2 alpha' subunit expression in vitro and rosiglitazone
      blocked induction of CK2 catalytic subunit expression by hypoxia in PA SMCs in
      vivo. CONCLUSION: We conclude that thiazolidinediones prevent PA remodeling in
      part by suppressing upregulation of CK2 and loss of CREB in PA SMCs.

PMID- 20147843
TI  - Diethylstilbestrol and other nonsteroidal estrogens: novel class of store
      operated calcium channel modulators.
AB  - BACKGROUND: Compounds with the stilbene pharmacophore and other nonsteroidal
      estrogens have previously been shown to inhibit thrombin-induced elevation of
      intracellular free calcium ([Ca]i) in human platelets. Thrombin elevates [Ca]i in
      platelets predominantly by activating a store-operated Ca entry (SOCE) mechanism,
      probably involving STIM1 and Orai1 although other components may be involved.
      METHODS: Human platelets were loaded with the Ca sensitive indicator fura-2,
      various concentrations of stilbene compounds and other nonsteroidal estrogens
      were added to the platelets, and thrombin was added to elevate [Ca]i. The degree
      of inhibition by each compound was determined at the peak increase in [Ca]i
      induced by thrombin. RESULTS: The additional compounds that were examined in the
      present study were analogs of diethylstilbestrol (DES), namely trans-resveratrol,
      hexestrol, tetrahydrochrysene (THC), indenestrol, isoflavones, flavones, and
      flavanones. DES, indenestrols, and substituted THC diols had the highest
      inhibitory activity. Dietary polyphenols were less active, and isoflavones were
      more active than flavones. Glycosides of flavones, flavanones, and isoflavones
      were inactive. Equol (a product of isoflavone metabolism) had low activity. Among
      the compounds with a stilbene moiety the presence of unsubstituted phenyl
      hydroxyls in the para- position were required for activity. Esterification of
      hydroxyls and bulky substituents at a hydroxyl group diminished or abolished
      activity. Presence of the ethyl side chains enhanced activity, and shortening or
      removal of these side chains was detrimental to activity. Presence of the
      conjugated double bound was necessary for activity. Reduction of the double bond
      (in fused rings such as equol, dihydrogenistein, indanestrol, or in open chain
      stilbene derivatives) or repositioning of this double bond outside the stilbene
      moiety was detrimental to activity, because phenyl rings are not co-planar and
      have to be at a certain angle to each other. CONCLUSION: DES likely represents
      the pharmacophore of this group of nonsteroidal estrogens as an inhibitor of SOCE
      in platelets.

PMID- 20147845
TI  - The effects of vinblastine on smooth muscle cells in vitro: evaluation of a
      therapeutic window for the treatment of restenosis.
AB  - The development of drug-eluting stents (DES) to combat the problem of in-stent
      restenosis has revolutionized interventional cardiology. However, concerns have
      emerged about the risk of late angiographic stent thromboses associated with DES.
      The evaluation and width of the therapeutic window of a particular DES system is
      of huge importance to its safety and efficacy. In this study, the effects of
      vinblastine, an antimitotic drug, on smooth muscle cells in vitro is analyzed.
      The change in levels of proliferation, activity, migration, and viability in
      human coronary artery smooth muscle cells was measured at a range of
      concentrations and over a number of time points. These findings were then
      compared with those of a previous study on the effects of vinblastine on
      endothelial cells, and an optimum working concentration range was evaluated. This
      study suggests that the concentration of vinblastine most appropriate in
      restenosis treatment would be between 0.1 and 1 nM. At this concentration,
      vinblastine exerts a distinct effect on smooth muscle cell proliferation without
      detrimental effects on endothelial cell viability. It was also found that
      vinblastine affects certain cellular activities such as migration in a threshold
      independent manner, suggesting that very low doses could be active against the
      processes of restenosis.

PMID- 20147844
TI  - Caspase inhibition modulates left ventricular remodeling following myocardial
      infarction through cellular and extracellular mechanisms.
AB  - BACKGROUND: Myocyte death occurs by necrosis and caspase-mediated apoptosis in
      myocardial infarction (MI). In vitro studies suggest caspase activation causes
      myocardial contractile protein degradation without inducing apoptosis. Thus,
      caspase activation may evoke left ventricular (LV) remodeling through independent
      processes post-MI. The effects of caspase activation on LV geometry post-MI
      remain unclear. This project applied pharmacologic caspase inhibition (CASPI) to
      a porcine model of MI. METHODS AND RESULTS: Pigs (34 kg) were instrumented to
      induce 60 minutes of coronary artery occlusion followed by reperfusion and a 7
      day follow-up period. Upon reperfusion, the pigs were randomized to saline (n =
      12) or CASPI (n = 10, IDN6734, 6 mg/kg i.v., then 6 mg/kg/h for 24 hours). Plasma
      troponin-I values were reduced with CASPI compared with saline at 24 hours post
      MI (133 +/- 15 vs. 189 +/- 20 ng/mL, respectively, P < 0.05). LV end-diastolic
      area (echocardiography) and interregional length (sonomicrometry) increased from
      baseline in both groups but were attenuated with CASPI by 40% and 90%,
      respectively (P < 0.05). Myocyte length was reduced with CASPI compared with
      saline (128 +/- 3 vs. 141 +/- 4 microm, respectively, P < 0.05). Plasma-free pro
      matrix metalloproteinase-2 values increased from baseline with CASPI (27% +/- 6%,
      P < 0.05) indicative of reduced conversion to active MMP-2. Separate in vitro
      studies demonstrated that activated caspase species cleaved pro-MMP-2 yielding
      active MMP-2 forms and that MMP activity was increased in the presence of
      activated caspase-3. CONCLUSIONS: CASPI attenuated regional and global LV
      remodeling post-MI and altered viable myocyte geometry. Caspases increased MMP
      activity in vitro, whereas CASPI modified conversion of MMP-2 to the active form
      in vivo. Taken together, the results of the present study suggest that the
      elaboration of caspases post-MI likely contribute to LV remodeling through both
      cellular and extracellular mechanisms.

PMID- 20147846
TI  - Comparative study of nifekalant versus amiodarone for shock-resistant ventricular
      fibrillation in out-of-hospital cardiopulmonary arrest patients.
AB  - BACKGROUND: In Japan, intravenous nifekalant (NIF) was often used for direct
      current cardioversion-resistant ventricular fibrillation (VF), until the use of
      intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of
      NIF and AMD has thus far not been compared for resuscitation. METHODS AND
      RESULTS: Between August 2007 and April 2009, 403 consecutive out-of-hospital
      patients with cardiopulmonary arrest were transferred to the Emergency Medical
      Service of Tokai University. Of these, 30 patients with first defibrillation
      failure or VF recurrence were enrolled for this NIF/AMD study. The final
      defibrillation success (and hospital survival rate) was 67% (10/15) in the AMD
      and 47% (7/15) in the NIF group. The discharge survival rate was 53% (8/15) in
      the AMD and 21% (4/15) in the NIF group (P = 0.06). Notably, all 4 survivors in
      the NIF group could take up normal daily life again, whereas this was restricted
      to only 2 patients from the 11 survivors in the AMD group. The difference is
      probably partly attributable to longer time from AMD administration to
      defibrillation success compared with NIF. In the cases of defibrillation failure,
      VF continued in 4/8 by NIF, however, asystole or pulseless electrical activity
      occurred in 4/5 patients by AMD. CONCLUSIONS: AMD may be borderline superior over
      NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary
      arrest. However, from the view point of preservation of brain function, NIF is
      not inferior to AMD for CPR.

PMID- 20147847
TI  - Inadvertent intrathecal administration of intravenous vincristine.

PMID- 20147848
TI  - Giant, dopamine secreting thoracoabdominal neuroblastoma in a 2-year-old: rapid
      preoperative blockade with labetalol.
AB  - Neuroblastomas secreting large amounts of catecholamines may require preoperative
      antihypertensive treatment to avoid intraoperative hypertensive crises as do
      pheochromocytomas. This is typically achieved with alpha-adrenergic followed if
      necessary by beta-adrenergic receptor blockade. Because of its predominant beta
      blockade, labetalol as a combined alpha-adrenergic and beta-adrenergic receptor
      antagonist is relatively contraindicated as sole and first agent in
      pheochromocytomas releasing epinephrine and norepinephrine. We report successful
      monotherapy with labetalol over 24 hours in a 2-year-old child with a giant
      thoracoabdominal neuroblastoma and predominant dopamine secretion.

PMID- 20147849
TI  - Free air intraperitoneally during chemotherapy for acute lymphoblastic leukemia:
      consider pneumatosis cystoides intestinalis.
AB  - Intraperitoneal free air in a child with acute lymphoblastic leukemia (ALL)
      treated with induction chemotherapy is an ominous sign suspective of
      gastrointestinal perforation. We report a case of pneumatosis cystoides
      intestinalis (PCI) with free intraperitoneal air without bowel perforation in a
      child with Down syndrome during ALL induction treatment. PCI is a physical sign
      characterized by gas-filled cysts of the submucosa or subserosa of the bowel that
      can lead to pneumoperitoneum. Clinical management of this case in respect to
      reported literature on PCI and specific characteristics of patients treated with
      ALL induction chemotherapy are discussed.

PMID- 20147850
TI  - Hematologic manifestations of brucellosis in children: 5 years experience of an
      anatolian center.
AB  - BACKGROUND: Brucellosis continues to be an important cause of fever in
      underdeveloped countries and in the rural areas of developed world. It is a
      multisystemic disease, associated with a wide variety of symptoms. A wide variety
      of symptoms, including hematologic abnormalities, such as anemia,
      thrombocytopenia, pancytopenia, dissemine intravascular coagulation, and
      leucopenia could be seen. The aim of the study is to review the hematologic
      findings of brucellosis in childhood. PROCEDURE: In this short study, the records
      of 146 children with brucellosis were evaluated for hematologic manifestation
      retrospectively. Among them, 9 patients had pancytopenia and 5 had brucella
      induced immune thrombocytopenia and were identified in a 5-year period between
      June 2004 and July 2009. RESULTS: Eight of the 9 patients with pancytopenia had
      Brucella melitensis isolated from blood cultures and/or bone marrow cultures, and
      all 9 patients had Brucella agglutination titers of at least 1:320. All patients
      with immune thrombocytopenia blood cultures were positive for Brucella. Except 1
      patient the pancytopenia in these patients regressed completely and their
      peripheral blood counts returned to normal after treatment of Brucella infection.
      One patient was not responding to the brucella treatment and underwent allogeneic
      hematopoietic stem cell transplantation. All patients with brucella-induced
      immune thrombocytic purpura were symptomatic and had severe thrombocytopenia,
      they were placed on intravenous gamma globulin for 2 days. Between day 3 and day
      5 platelet counts increased in these patients. CONCLUSION: Brucellosis should be
      considered as a possible diagnosis among patients with pancytopenia and immune
      thrombocytopenic purpura in endemic regions.

PMID- 20147851
TI  - Abdominal tuberculosis mimicking childhood lymphoma: a case report.

PMID- 20147852
TI  - Medulloblastoma harbor somatic mitochondrial DNA mutations in the D-loop region.
AB  - Despite the growing knowledge on molecular risk factors of the most common
      malignant brain tumor in childhood, medulloblastoma, its biology remains only
      partially understood. A previous study investigating the entire mitochondrial
      genome of medulloblastoma revealed a number of somatic mutations in tumor and
      corresponding cerebrospinal fluid samples. In our present study we sought to
      corroborate these results on somatic and germ line mutations by comparing the
      complete mitochondrial genome sequences of medulloblastoma tissue in a further
      cohort of patients. Analysis of the entire mitochondrial genome by temporal
      temperature gel electrophoresis and direct sequencing revealed 6 somatic
      mutations in 6 of 15 medulloblastoma. All changes were insertions, deletions, or
      substitutions restricted to the np 303 to 315 poly-C tract of the D-loop region.
      Three were changes from heteroplasmy to homoplasmy. Two were changes from
      heteroplasmy to heteroplasmy and one mutation represented a change from
      homoplasmy to heteroplasmy. In addition, 25 distinct germ line variations were
      identified. These results are in support of our previous findings on frequency of
      somatic mitochondrial mutations in medulloblastoma. Somatic alterations were
      found only in the hypervariable D-loop region, supporting the idea that these
      control regions contain hot spots for both, germ line variations and somatic
      alterations of the mitochondrial genome.

PMID- 20147853
TI  - A case of mild thalassemic syndrome caused by interaction of Hb Adana with an
      alpha+-thalassemia deletion.

PMID- 20147854
TI  - Salivary flow rate, calcium, urea, total protein, and amylase levels in fanconi
      anemia.
AB  - OBJECTIVES: Fanconi anemia (FA) is a genetic disease characterized by a
      chromosomal instability that develops a progressive pancitopenia, leukemia,
      and/or solid tumors. Nevertheless, it is unknown if this illness induces changes
      on the salivary gland parenchyma and function. The aim of this study was to
      assess the stimulated salivary flow rate (SSFR) and calcium, urea, total protein,
      and amylase levels in saliva of FA patients. METHODS: Stimulated whole saliva was
      collected from 34 randomly selected FA patients and 34 age-matched and sex
      matched controls. Both samples were analyzed for salivary flow rate, calcium,
      urea, total proteins, and amylase. The SSFR was analyzed by gravimetric method
      and calcium, urea, total protein, and amylase concentrations were realized by
      chemistry tests. RESULTS: Mean values of SSFR for experimental and control groups
      were, respectively, 0.5 mL/min and 0.8 mL/min (P<0.05). Calcium concentration was
      36% (P<0.05) and urea concentration was 21% (P<0.01) lower in the FA group saliva
      compared with saliva from the controls. The saliva concentration of amylase was
      almost equal in both groups. CONCLUSIONS: FA patients may exhibit significant
      changes in SSFR, calcium, and urea concentration of saliva.

PMID- 20147855
TI  - Primary Ewing's sarcoma of the cervical vertebra: one case report and literature
      review.
AB  - Primary Ewing's sarcoma of the cervical vertebra is extremely rare. However, it
      is very important for radiologists to be aware of it to be able to provide timely
      diagnosis and therefore orient the treatment planning of the disease. The purpose
      of this study is to describe the imaging features of this tumor.

PMID- 20147856
TI  - Randomized phase II study of two different schedules of gemcitabine and oral S-1
      in chemo-naive patients with advanced non-small cell lung cancer.
AB  - INTRODUCTION: This study was conducted to evaluate the efficacy and safety and to
      compare dosing schedules of gemcitabine combined with S-1 in chemo-naive non
      small cell lung cancer patients. METHODS: Patients with chemo-naive stage IIIB/IV
      non-small cell lung cancer were randomized into two treatment arms. Patients were
      given oral S-1 (60 mg/m/d, twice a day) from days 1 to 14 with gemcitabine (1000
      mg/m/d) on days 1 and 8 (arm A) or on days 8 and 15 (arm B). This cycle was
      repeated every 21 days. RESULTS: A total of 80 patients were entered in this
      trial. The primary end point of this study was response rate. The response rates
      of arm A and arm B were 22.0 and 28.9%, respectively (p = 0.606). Median time to
      treatment failure in arm A was 3.6 months and 4.8 months in arm B. Median time to
      progression in arm A was 4.1 months and 5.5 months in arm B. Median survival time
      in arm A and arm B was 15.5 months and 18.8 months, respectively. The toxicity
      profile was relatively mild and did not differ very much between two arms.
      CONCLUSION: The combination of gemcitabine and S-1 was determined to be feasible
      and effective for advanced non-small cell lung cancer. We selected arm B for
      further studies because of its higher response rate and survival data.

PMID- 20147857
TI  - Population-based incidence of vulvar and vaginal melanoma in various races and
      ethnic groups with comparisons to other site-specific melanomas.
AB  - Little is known on the difference in the incidence of vulvar and vaginal
      melanomas in various racial/ethnic groups. Population-based incidence of these
      melanomas in Asian and Hispanic individuals is almost unknown. Using 1992-2005
      data provided by the National Cancer Institute's Surveillance, Epidemiology, and
      End Results Program, we calculated age-adjusted incidence rates of vulvar and
      vaginal melanomas in various racial/ethnic groups. From 1992 to 2005, there were
      324 vulvar melanomas and 125 vaginal melanomas diagnosed in this group. The
      annual age-adjusted incidence rates (per million female population) of vulvar and
      vaginal melanomas in the different racial/ethnic groups was 0.87 (Blacks), 0.75
      (American-Indian), 1.03 (Asians and Pacific Islanders), 1.22 (Hispanics), and
      1.90 (non-Hispanic Whites). The overall white/black incidence ratio in vulvar and
      vaginal melanomas was 3.14 : 1 and 1.02 : 1, respectively; which is much less
      than that of cutaneous melanoma (13 : 1-17 : 1) and uveal melanoma (18 : 1) and
      is similar to that of conjunctival melanoma (2.6 : 1) and other mucosal melanomas
      (2.1 : 1-2.3 : 1). The low racial difference in vulvar and vaginal melanomas (as
      well as conjunctival and other mucosal melanomas) may be determined by their
      microenvironment factors (all originate from mucosa or semi-mucosa tissues). The
      incidence of vulvar and vaginal melanomas has does not increased in recent
      decades or toward the south (more sun exposure), indicating that ultraviolet
      radiation is not a causative factor in these melanomas. The slight decrease of
      incidence of vulvar melanoma in dark pigmented individuals may be related to the
      biochemical protective effects of melanin (as an antioxidant) rather than their
      photo-screen effects.

PMID- 20147858
TI  - Testosterone recruits new aromatase-imunoreactive cells in neonatal quail brain.
AB  - It was shown earlier that, in Japanese quail the mechanism controlling the
      induction by testosterone of aromatase activity develops between embryonic days
      10 and 14. The cellular processes underlying this activation have, however, not
      been investigated in detail. Here, we demonstrate that the increase in aromatase
      activity observed in neonates treated with testosterone propionate between
      postnatal days 1 and 3 results from the recruitment of additional populations of
      aromatase-immunoreactive cells that were not expressing the enzyme at detectable
      levels before. This recruitment concerns all brain nuclei normally expressing the
      enzyme even if it is more prominent in the ventromedial hypothalamus than in
      other nuclei.

PMID- 20147859
TI  - ERP effects of change localization, change identification, and change blindness.
AB  - Change blindness is the failure to detect changes in visual scenes. Changes can
      elicit phenomenologically different perceptual experiences, possibly relating to
      different mechanisms: changes may be entirely missed, merely detected, located,
      or identified. We presented sequences of meaningful objects, one of which could
      change between the presentations. Changes had to be located and identified.
      Observers sometimes located the change without knowing which object had changed.
      However, effects of localization with and without identification were remarkably
      similar on a sequence of event-related potential components (including change
      related positivity and N2pc). Only a late contralateral positivity was found
      exclusively for identified changes, indicating that change localization and
      change identification initially rely on a common processing sequence and differ
      only at later stages.

PMID- 20147860
TI  - Reward acts as a signal to control delay-period activity in delayed-response
      tasks.
AB  - Prefrontal delay-period activity represents a neural mechanism for the active
      maintenance of information and needs to be controlled by some signal to
      appropriately operate working memory. To examine whether reward-delivery acts as
      this signal, the effects of delay-period activity in response to unexpected
      reward-delivery were examined by analyzing single-neuron activity recorded in the
      primate dorsolateral prefrontal cortex. Among neurons that showed delay-period
      activity, 34% showed inhibition of this activity in response to unexpected reward
      delivery. The delay-period activity of these neurons was affected by the
      expectation of reward-delivery. The strength of the reward signal in controlling
      the delay-period activity is related to the strength of the effect of reward
      information on the delay-period activity. These results indicate that reward
      delivery acts as a signal to control delay-period activity.

PMID- 20147861
TI  - Adult neurogenesis is unaffected by a functional knock-out of MHC class I in
      mice.
AB  - The major histocompatibility complex (MHC) class I has a role in the regulation
      of immune responses and has been implicated recently in neural plasticity and
      neurogenesis. We therefore sought to investigate in functional MHC class I
      knockout mice, transporter associated with antigen processing 1 (TAP1) KO,
      whether there are alterations in adult neurogenesis. We found no significant
      differences in cell proliferation or neurogenesis in either the dentate gyrus or
      subventricular zone, in TAP1 KO versus wild-type mice at several different time
      points. Our results do not support a role for MHC class I in adult neurogenesis,
      although it may still have a role in the maturation and integration of newborn
      neurons.

PMID- 20147862
TI  - Imaging of radioiodine-labeled KH901, a tumor-specific oncolytic recombinant
      adenovirus, in nude mice with human hepatocellular carcinoma.
AB  - OBJECTIVE: To study the biodistribution and imaging of I/I-labeled KH901, a tumor
      specific oncolytic recombinant adenovirus, in nude mice bearing human
      hepatocarcinoma. METHODS: KH901 was labeled with I/I according to the N
      bromosuccinimide labeling method. The activity of granulocyte-macrophage colony
      stimulating factor was determined by enzyme-linked immunosorbent assay. After I
      KH901 was injected into the tumor, the label was followed in different organs and
      tumor tissues in nude mice with hepatocellular carcinoma. I-KH901 was injected
      directly into the tumor of nude mice bearing hepatocellular carcinoma, and their
      concentrations were detected at different times on radionuclide images. RESULTS:
      The radiochemical purity of I/I-KH901 was over 95%. I-KH901 stimulated massive
      expression of granulocyte-macrophage colony-stimulating factor in tumor cells.
      Twenty-four hours after the addition of I-KH901, the concentrations of
      granulocyte-macrophage colony-stimulating factor were 183.27+/-6.90 and 20.44+/
      0.77 pg/ml in tumor and normal cells, respectively. I-KH901 was mainly
      distributed in the tumor and had a longer retention time, which was 14.93%ID/g at
      24 h. Radionuclide imaging showed that the radioactive retention of I-KH901 in
      the tumor was significant. The tumor was shown clearly in the whole-body scan at
      2 h after injection. CONCLUSION: I or I-KH901 concentrates specifically at the
      tumor site, which makes it a novel drug (combination of oncolytic adenovirus and
      radionuclide therapies) for the treatment of cancer.

PMID- 20147863
TI  - Extended application of 99mTc-mebrofenin cholescintigraphy with cholecystokinin
      in the evaluation of abdominal pain of hepatobiliary and gastrointestinal origin.
AB  - OBJECTIVE: To explore the extension of cholecystokinin-cholescintigraphy in the
      evaluation of abdominal pain. METHODS: A total of 1554 patients with abdominal
      pain underwent Tc-mebrofinin cholescintigraphy. Gallbladder ejection fraction was
      obtained with cholecystokinin (sincalide) and abdominal pain was graded. RESULTS:
      Fourteen different types of hepatobiliary and gastrointestinal motility disorders
      were identified. Biliary dyskinesia was found in 453 patients, septate
      gallbladder in 33, and duodeno-gastric bile reflux in 46 patients. Sincalide
      induced intestinal hyperperistalsis alone was found in 65 and in combination with
      other diseases in 64 patients. Abdominal pain was mild to moderate in intensity,
      and occurred in 50-60% of patients with abnormal gallbladder function. Severe
      abdominal pain was usually associated with intestinal hyperperistalsis.
      CONCLUSION: Tc-mebrofinin cholescintigraphy enables the identification of
      motility disorders of the gastrointestinal and hepatobiliary tract, and post
      sincalide abdominal pain in most cases can be assigned to functional abnormality
      of the gallbladder or/and intestine.

PMID- 20147864
TI  - Remote programming of cochlear implants: a telecommunications model.
AB  - OBJECTIVE: Evaluate the effectiveness of remote programming for cochlear
      implants. STUDY DESIGN: Retrospective review of the cochlear implant performance
      for patients who had undergone mapping and programming of their cochlear implant
      via remote connection through the Internet. METHODS: Postoperative Hearing in
      Noise Test and Consonant/Nucleus/Consonant word scores for 7 patients who had
      undergone remote mapping and programming of their cochlear implant were compared
      with the mean scores of 7 patients who had been programmed by the same
      audiologist over a 12-month period. Times required for remote and direct
      programming were also compared. The quality of the Internet connection was
      assessed using standardized measures. Remote programming was performed via a
      virtual private network with a separate software program used for video and audio
      linkage. RESULTS: All 7 patients were programmed successfully via remote
      connectivity. No untoward patient experiences were encountered. No statistically
      significant differences could be found in comparing postoperative Hearing in
      Noise Test and Consonant/Nucleus/Consonant word scores for patients who had
      undergone remote programming versus a similar group of patients who had their
      cochlear implant programmed directly. Remote programming did not require a
      significantly longer programming time for the audiologist with these 7 patients.
      CONCLUSION: Remote programming of a cochlear implant can be performed safely
      without any deterioration in the quality of the programming. This ability to
      remotely program cochlear implant patients gives the potential to extend cochlear
      implantation to underserved areas in the United States and elsewhere.

PMID- 20147865
TI  - Long-term reliability of pediatric cochlear implants.
AB  - OBJECTIVE: This study defines a method of interpreting cumulative survival rate
      for pediatric cochlear implants (CIs) that is applicable to the time span when
      hearing is most critical for speech and language development. In addition, it
      applies this method to published data reporting pediatric device failures.
      PATIENTS: Pediatric CI recipients for whom cumulative survival rates have been
      published were the patient population, consisting of 2009 recipients.
      INTERVENTION: Pediatric cochlear implantation. MAIN OUTCOME MEASURE: The main
      outcome measure was cumulative survival rate (CSR), defined as the percentage of
      CIs that are functional, calculated as a function of time after implantation.
      This measure was reported for time periods from 4 to 19 years for devices made by
      3 CI manufacturers. RESULTS: Cumulative survival rates at 18 years were predicted
      by extrapolating regression functions to published data. Predicted 18-year CSRs
      express the likelihood that the device will function throughout child development
      after early implantation. Devices with titanium casing exhibited 18-year CSRs
      from 0.900 to 0.988 for a monolateral implants and from 0.810 to 0.976 for both
      bilateral implants. Devices with ceramic casings had 18-year CSRs of 0.740 to
      0.944 for monolateral implants and 0.548 to 0.871 for bilateral implants.
      CONCLUSION: Use of 18-year CSRs allows comparison of survival rates obtained from
      data over different time intervals and is based on the time course of normal
      development. These values provide a conservative and meaningful estimate of
      device reliability for pediatric recipients. The higher failure rates of ceramic
      devices for children are likely due to the greater incidence of head trauma from
      impact and/or leakage from cracked casings seen in this population.

PMID- 20147867
TI  - Acoustic neuroma growth: a systematic review of the evidence.
AB  - AIM: To undertake a systematic review of the literature on acoustic neuroma
      growth. Predictors of growth were also explored. MATERIALS AND METHODS: A
      comprehensive search was conducted to identify the relevant literature. The
      search yielded 2,455 papers. All titles were reviewed by 2 of the authors, and
      finally, 41 papers were found reporting data pertinent to growth. RESULTS: The
      percentage of acoustic neuromas exhibiting growth ranges widely from 18 to 73%.
      The percentage of tumors reported not to grow for some years after diagnosis
      ranges from 9 to 75%. Some (usually less than 10%, but up to 22%) may get
      smaller. No reliable predictors of growth have been identified. The mean growth
      rate for all tumors varies between 1 and 2 mm/yr, and for only those that grow,
      between 2 and 4 mm/yr. However, there are cases with significant regression or
      exceptional growth (exceeding 18 mm/yr). There are various patterns of growth,
      and a tumor that shows growth may stop doing so and vice versa. Finally, some
      tumors that have been stable for many years can exhibit tumor growth. CONCLUSION:
      The growth pattern of acoustic neuromas is variable and incompletely understood.
      As much as 75% of tumors have been reported to show no growth, supporting a "wait
      and rescan" policy in many patients, although there are no reliable predictors of
      tumor behavior, and some tumors may grow rapidly. Primary longitudinal studies
      are needed to better define the natural history and limit unnecessary
      interventions.

PMID- 20147866
TI  - Consensus panel on a cochlear coordinate system applicable in histologic,
      physiologic, and radiologic studies of the human cochlea.
AB  - HYPOTHESIS: An objective cochlear framework, for evaluation of the cochlear
      anatomy and description of the position of an implanted cochlear implant
      electrode, would allow the direct comparison of measures performed within the
      various subdisciplines involved in cochlear implant research. BACKGROUND:
      Research on the human cochlear anatomy in relation to tonotopy and cochlear
      implantation is conducted by specialists from numerous disciplines such as
      histologists, surgeons, physicists, engineers, audiologists, and radiologists. To
      allow accurate comparisons between and combinations of previous and forthcoming
      scientific and clinical studies, cochlear structures and electrode positions must
      be specified in a consistent manner. METHODS: Researchers with backgrounds in the
      various fields of inner ear research as well as representatives of the different
      manufacturers of cochlear implants (Advanced Bionics Corp., Med-El, Cochlear
      Corp.) were involved in consensus meetings held in Dallas, March 2005, and
      Asilomar, August 2005. Existing coordinate systems were evaluated, and requisites
      for an objective cochlear framework were discussed. RESULTS: The consensus panel
      agreed upon a 3-dimensional, cylindrical coordinate system of the cochlea using
      the "Cochlear View" as a basis and choosing a z axis through the modiolus. The
      zero reference angle was chosen at the center of the round window, which has a
      close relationship to the basal end of the Organ of Corti. CONCLUSION: Consensus
      was reached on an objective cochlear framework, allowing the outcomes of studies
      from different fields of research to be compared directly.

PMID- 20147869
TI  - The association between lumbar disc degeneration and low back pain: the influence
      of age, gender, and individual radiographic features.
AB  - STUDY DESIGN: Cross-sectional open population based study (nested in a
      prospective cohort study). OBJECTIVE: To explore the association of the different
      individual radiographic features, including osteophytes and disc space narrowing,
      with self-reported low back pain (LBP). Different definitions of lumbar disc
      degeneration with self-reported LBP and disability were considered in a large
      open population sample. Furthermore, in order to disentangle the discrepancies in
      reported strength of the associations, we characterized the frequency of the
      different individual radiographic features of lumbar disc degeneration and
      definitions of lumbar disc degeneration, as well as their association with LBP
      status, by age, gender, and vertebral level. SUMMARY OF BACKGROUND DATA:
      Currently within the literature, there have been no studies that have explored
      different definitions of lumbar disc degeneration and their association with LBP
      within one study sample. METHODS: The intervertebral disc spaces (L1/2 to L5-S1)
      were evaluated for the presence and severity of anterior osteophytes and disc
      space narrowing using a semiquantitative score (grade 0-3). Logistic regression
      was used to determine the association between these individual radiographic
      features of lumbar disc degeneration and different definitions of lumbar disc
      degeneration for LBP. RESULTS: Lumbar radiographs were scored for 1204 men, and
      1615 women. Osteophytes were the most frequent radiographic feature observed,
      with men having the greatest frequency. Disc space narrowing was more frequent in
      women than men. Both radiographic features increased in frequency with age.Disc
      space narrowing appeared more strongly associated with LBP than osteophytes,
      especially in men (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.4-2.8).
      Disc space narrowing at 2 or more levels appeared more strongly associated with
      LBP than disc space narrowing at only 1 level (OR = 2.4; 95% CI: 1.6-3.4). After
      excluding level L5-S1, the strength of almost all associations increased.
      CONCLUSION: We are the first to report different possible lumbar disc
      degeneration definitions and their associations with LBP. Disc space narrowing at
      2 or more levels appeared more strongly associated with LBP than other
      radiographic features, especially after excluding level L5-S1.

PMID- 20147870
TI  - Posterior spinal artery infarct due to patent foramen ovale: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report the first case of posterior
      spinal artery (PSA) infarct due to patent foramen ovale (PFO). SUMMARY OF
      BACKGROUND DATA: Infarct in the territories of PSA are very rare: till now 38
      cases are reported in the literature. Moreover only 1 case of spinal cord
      infarction was attributed to paradoxical embolism through PFO, but in the
      anterior spinal artery territory. METHODS: A 60-year-old woman was hospitalized
      for sudden numbness of the right leg. Neurologic examination revealed right leg
      mild paresis and loss of proprioception and dysesthesia at T11. Spine-MRI showed
      T5-T7 posterolateral cord ischemia. Transesophageal echocardiography disclosed a
      PFO with severe right-left shunt confirmed by transcranial Doppler. RESULTS:
      During the hospitalization she was treated with oral-500 mg ticlopidine, because
      of a mild allergic reaction to acetylsalicylic acid. No steroids were
      administrated. Physiotherapy was performed daily. Motor and urinary symptoms
      disappeared in 20 days. At 1-month clinical follow-up only suspended dysesthesia
      on the right side was present. At 3 months follow-up spine-MRI showed no signal
      abnormalities within the spinal cord but the patient still complained of
      dysesthesia. The therapy was changed to oral 75 mg clopidogrel, cause of
      leucopoenia. At 1-year follow-up dysesthesia was still present, but less
      complaining and no recurrence and adverse effect due to clopidogrel therapy were
      reported. CONCLUSION: This report describe a case of acute nontraumatic
      myelopathy. At 4 days after onset, PSA infarct was diagnosed on the basis of
      neurologic findings and MR images. After extensive diagnostic work-up, we were
      able to identify only PFO, so it was the first case of PSA due to probable
      paradoxical embolism. The patient was treated with antiplatelet therapy with good
      recovery and no recurrence at 1-year follow-up.

PMID- 20147868
TI  - Intratympanic steroid prevents long-term spiral ganglion neuron loss in
      experimental meningitis.
AB  - HYPOTHESIS: Intratympanic steroid treatment prevents hearing loss and cochlear
      damage in a rat model of pneumococcal meningitis. BACKGROUND: Sensorineural
      hearing loss is a long-term complication of meningitis affecting up to a third of
      survivors. Streptococcus pneumoniae is the bacterial species most often
      associated with a hearing loss. METHODS: Rats were randomly assigned to 3
      treatment groups: a group treated with intratympanic betamethasone and 2 control
      groups treated with either intratympanic or systemic saline. Treatment was
      initiated 21 hours after infection and repeated once a day for 3 days. Hearing
      loss and cochlear damage were assessed by distortion product otoacoustic
      emissions, auditory brainstem response at 16 kHz, and spiral ganglion neuron
      density. RESULTS: Fifty-six days after infection, auditory brainstem response
      showed no significant differences between groups, and distortion product
      otoacoustic emissions showed significant hearing loss at the low frequencies in
      animals treated with intratympanic steroid compared with animals treated with
      systemic saline (p < 0.05; Mann-Whitney test). However, intratympanic steroid
      significantly increased the number of viable neurons in the spiral ganglion
      compared with both intratympanic and systemic saline (p = 0.0082 and p = 0.0089;
      Mann-Whitney test). Histology revealed fibrosis of the tympanic membrane and
      cavity in steroid-treated animals, which plausibly caused the low-frequency
      hearing loss. CONCLUSION: Intratympanic betamethasone treatment prevents long
      term spiral ganglion neuron loss in experimental pneumococcal meningitis. This
      finding is clinically relevant in relation to post-meningitic hearing
      rehabilitation by cochlear implantation. However, the drug instillation in the
      middle ear induced local fibrosis and a concurrent low-frequency hearing loss.

PMID- 20147871
TI  - Chronic myelopathy associated to intramedullary cysticercosis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: Discuss an isolated intramedullary
      neurocysticercosis (NCC) case in an adult patient with chronic progressive onset
      myelopathic symptomatology with clinical, radiologic, and pathologic correlation.
      SUMMARY OF BACKGROUND DATA: NCC is the most common parasitic infection in the
      central nervous system. Spinal NCC belongs to the group of extraparenchymal forms
      of NCC and it is considered an extremely rare form characterized by a distinct
      clinical entity due to mass effect on the spinal cord. METHODS: Description of a
      62-year-old male patient case who presented with chronic but progressive low cord
      myelopathy who underwent radiologic investigation through magnetic resonance
      imaging depicting a thoracic intramedullary cystic lesion at level T11. RESULTS:
      Surgical excision of the intramedullary lesion was preformed and pathologic study
      confirmed a cysticercus. There was complete resolution of the neurologic symptoms
      and follow-up monitoring was unremarkable. CONCLUSION: Although intramedullary is
      a rare NCC location, it should be considered in the differential diagnosis in
      high-risk populations especially when cord compression and myelopathy symptoms
      are present. Magnetic resonance imaging remains the investigative and follow-up
      modality of choice, and promptly lesion recognition is fundamental for surgical
      planning and to improve the patient outcome.

PMID- 20147872
TI  - Coil embolization of a lumbar artery to control vascular injury during
      intradiscal surgery.
AB  - STUDY DESIGN: Case study. OBJECTIVE: To emphasize the role that interventional
      radiology can perform in stemming bleeding to vascular structures injured during
      spine surgery without altering patient position. SUMMARY AND BACKGROUND DATA:
      Injury to the lumbar artery or aorta may occur during lumbar disc surgery.
      Occasionally the site of bleeding may not be readily identifiable or accessible
      through the surgical incision. Interventional radiology techniques may be
      employed to help locate and stop these difficult to locate vascular structures
      without changing a patient position. METHODS: A 48-year-old woman undergoing L4
      L5 lumbar hemilaminectomy and discectomy secondary to a herniated disc sustained
      an injury to a right L3 lumbar artery. Several liters of blood were lost in an
      attempt to surgically locate and repair the injury to the lumbar artery. A
      literature search identified the potential severity and treatment options.
      RESULTS: An interventional radiologist was called for and he was able to
      angiographically locate the source of bleeding and stem its source using coil
      embolization of the lumbar artery. CONCLUSION: Whenever there is bleeding from an
      inaccessible site, consultation with an interventional radiologist to perform an
      intraoperative coil embolization of the injured vessel should be done especially
      if a resort to an anterior abdominal approach would permit uncontrolled bleeding.

PMID- 20147873
TI  - Distractive force relative to initial graft compression in an in vivo anterior
      cervical discectomy and fusion model.
AB  - STUDY DESIGN: An in vivo biomechanical anterior cervical discectomy and
      instrumented fusion (ACDFI) model employing a calibrated distractor and a
      subminiature load cell used to intraoperatively measure distractive force across
      the discectomy site and subsequent compressive force across the interbody load
      cell following distractor removal. OBJECTIVE: To determine the relationship
      between the distractive force and resultant initial graft compression in an in
      vivo ACDFI model. SUMMARY OF BACKGROUND DATA: The relationship between the
      distractive force and subsequent graft compression following distractor removal
      has not been studied in an in vivo ACDFI model. The consequences of over or under
      distraction and its subsequent effect on graft compression with regards to axial
      neck pain, endplate failure with graft subsidence, and fusion rates is an area of
      clinical significance for ACDFI. METHODS: Intraoperative measurements were
      obtained from 17 discectomy sites in 12 patients undergoing one and two level
      ACDFI. Informed consent was obtained from all subjects before surgery. A
      calibrated Caspar distractor was used to measure the distraction across the
      discectomy site and a subminiature interbody load cell was placed into the
      discectomy site and used to measure the resultant initial compressive force
      following distractor removal. The statistical significance and correlation
      between the distractive force across the discectomy site and the subsequent
      compressive force across the load cell were investigated with the Pearson
      correlation coefficient. RESULTS: The average distractive force across the
      discectomy site was 33.5 +/- 11.6 lbs and the subsequent compressive force across
      the interbody load cell was 16.9 +/- 5.9 lbs following distractor removal. The
      Pearson correlation coefficient was r = 0.912 (P < 0.0005). The data showed a
      statistically significant linear correlation between the distractive force and
      the subsequent compressive force across the range of distraction investigated.
      CONCLUSION: This study demonstrated a statistically significant linear
      correlation between the distractive force applied across the discectomy site and
      the subsequent compressive force across a load cell placed in the interbody space
      following distractor removal in an in vivo ACDFI model.

PMID- 20147874
TI  - Score distribution of the scoliosis research society-22 questionnaire in
      subgroups of patients of all ages with idiopathic scoliosis.
AB  - STUDY DESIGN: Cross-sectional measurement study. OBJECTIVE: To analyze the score
      distribution of the Scoliosis Research Society (SRS)-22 questionnaire domains and
      items for patients with idiopathic scoliosis (IS) of all ages. SUMMARY OF
      BACKGROUND DATA: Scoliosis-related quality-of-life questionnaires have
      demonstrated high ceiling effects in younger patients. However, the score
      distribution has not been examined thoroughly in other clinically relevant IS
      subgroups. METHODS: The SRS-22 was completed by 173 females with IS. The
      proportions of ceiling effects, floor effects, of patients scoring greater than
      or equal to 4 out of 5 and the box plots of the score distribution for each
      domain and item were compared between subgroups. Subgroups were formed based on
      age (k = 4), management (k = 6), curve severity (k = 3), and curve type (k = 4).
      RESULTS: Domain ceiling effects varied between 0% and 23.1%. Domain floor effects
      were observed only for Self-image (<7%) and Satisfaction (<12%). Only Pain and
      Satisfaction showed moderate (>20%) ceiling effects. Ceiling effects for Pain and
      Mental Health decreased with increasing age (P < 0.05). Pain ceiling effects
      decreased and Satisfaction ceiling effects increased from least to most invasive
      management (P < 0.05), but no differences were found among Cobb severity or curve
      types subgroups. Of the 22 items, 9 had major (>or=50%) ceiling effects and 11
      had moderate ceiling effects. Most subgroups (14/16) had 4 to 6 items with major
      ceiling effects. The following items had major ceiling effects in the majority of
      subgroups: Function, 9 and 15; Pain, 11 and 17; and Self-image, 14. CONCLUSION:
      Most SRS-22 domains had acceptable levels of ceiling effects (<20%) in the
      majority of the subgroups examined. However, more sensitive measurements may be
      needed to supplement the SRS-22 in assessing Pain in patients below 18 years or
      Satisfaction after surgery.

PMID- 20147875
TI  - The efficacy of a short education program and a short physiotherapy program for
      treating low back pain in primary care: a cluster randomized trial.
AB  - STUDY DESIGN: Cluster randomized clinical trial. OBJECTIVE: To assess the
      efficacy of a short education program and short physiotherapy program for
      treating low back pain (LBP) in primary care. SUMMARY OF BACKGROUND DATA: There
      is sparse evidence on the effectiveness of education and physiotherapy programs
      that are short enough to be feasible in primary care. METHODS: Sixty-nine primary
      care physicians were randomly assigned to 3 groups and recruited 348 patients
      consulting for LBP; 265 (79.8%) were chronic. All patients received usual care,
      were given a booklet and received a consistent 15 minutes group talk on health
      education, which focused on healthy nutrition habits in the control group, and on
      active management for LBP in the "education" and "education + physiotherapy"
      groups. Additionally, in the "education + physiotherapy" group, patients were
      given a second booklet and a 15-minute group talk on postural hygiene, and 4 one
      hour physiotherapy sessions of exercise and stretching which they were encouraged
      to keep practicing at home. The main outcome measure was improvement of LBP
      related disability at 6 months. Patients' assessment and data analyses were
      blinded. RESULTS: During the 6-month follow-up period, improvement in the
      "control" group was negligible. Additional improvement in the "education" and
      "education + physiotherapy" groups was found for disability (2.0 and 2.2 Roland
      Morris Questionnaire points, respectively), LBP (1.8 and 2.10 Visual Analogue
      Scale points), referred pain (1.3 and 1.6 Visual Analogue Scale points),
      catastrophizing (1.6 and 1.8 Coping Strategies Questionnaire points), physical
      quality of life (2.9 and 2.9 SF-12 points), and mental quality of life (3.7 and
      5.1 SF-12 points). CONCLUSION: The addition of a short education program on
      active management to usual care in primary care leads to small but consistent
      improvements in disability, pain, and quality of life. The addition of a short
      physiotherapy program composed of education on postural hygiene and exercise
      intended to be continued at home, increases those improvements, although the
      magnitude of that increase is clinically irrelevant.

PMID- 20147876
TI  - Unknown case: part 1.

PMID- 20147877
TI  - Is activation of the back muscles impaired by creep or muscle fatigue?
AB  - STUDY DESIGN: Intervention study on healthy human subjects. OBJECTIVE: To
      determine whether reflex activation of the back muscles is influenced by muscle
      fatigue or soft tissue creep in the spine. SUMMARY OF BACKGROUND DATA: Reflex
      contraction of the back muscles normally acts to limit spinal flexion, and hence
      protect the underlying spine from injury. However, repeated flexion allows
      bending moments on the spine to increase. Impaired reflexes as a result of
      fatigue or soft tissue creep may be contributing factors. METHODS: A total of 15
      healthy volunteers (8 females/7 males aged 23-55 years) underwent 2
      interventions, on separate days: (a) sitting flexed for 1 hour to induce creep
      and (b) performing the Biering-Sorensen test to induce back muscle fatigue.
      Before and after each intervention, reflex activation of the erector spinae in
      response to sudden trunk flexion (initiated by a Kin-Com dynamometer) was
      monitored bilaterally at T10 and L3 using surface electromyography (EMG)
      electrodes. These recordings indicated the onset latency of reflex activation,
      the peak EMG, and time to peak, at each site. Measurements before and after each
      intervention and between muscle sites were compared using a 2-way repeated
      measures Analysis of Variance. RESULTS: Spinal creep was confirmed by an increase
      in maximum flexion of 2.3 degrees +/- 2.5 degrees (P = 0.003), and fatigue by a
      significant fall in median frequency at one or more sites. Following creep, onset
      latency increased from 60 +/- 12 milliseconds to 96 +/- 26 milliseconds (P <
      0.001) but there was no change in peak EMG or time to peak EMG. Differences
      between sites (P = 0.004) indicated greater latencies in lumbar compared to
      thoracic regions, especially after creep. Muscle fatigue had no significant
      effects on any of the measured parameters. CONCLUSION: Prolonged spinal flexion
      can impair sensorimotor control mechanisms and reduce back muscle protection of
      the underlying spine. The effect is due to time-dependent "creep" in soft tissues
      rather than muscle fatigue.

PMID- 20147878
TI  - Treatment of chronic low back pain: a randomized, clinical trial comparing group
      based multidisciplinary biopsychosocial rehabilitation and intensive individual
      therapist-assisted back muscle strengthening exercises.
AB  - STUDY DESIGN: A stratified randomized single-blinded clinical trial. OBJECTIVE:
      To compare the efficacies of 2 active therapies for chronic low back pain (CLBP).
      SUMMARY OF BACKGROUND DATA: Both a multidisciplinary biopsychosocial
      rehabilitation program and an intensive individual therapist-assisted back muscle
      strengthening exercise program used in Denmark have been reported to be effective
      for the treatment of CLBP. METHODS: A total of 286 patients with CLBP were
      randomized to either a group-based 12-week program comprising 73 hours of
      therapist exposure (approximately 12 h/patient): 35 hours of hard physical
      exercise, 22 hours of light exercise/occupational therapy, and 16 hours of
      education (group A) or a 12-week program comprising 1 hour of personal training
      twice a week, i.e., therapist exposure 24 h/patient (group B). At baseline and at
      3, 6, 12, and 24 months, patients filled out questionnaires on pain (visual
      analogue scale [VAS]-pain average, which was the primary outcome measure), Roland
      Morris disability questionnaire, global perceived outcome, and 36-Item Short-Form
      General Health Survey. Data were analyzed using the intention-to-treat principle.
      RESULTS: Of the 286 patients, 14 patients did not start treatment. Of the
      remaining patients, 25 (9%) dropped out of therapy. The 2 groups were comparable
      regarding baseline characteristic. After treatment, significant improvements were
      observed with regard to pain, disability, and most of the quality of life
      dimensions. These effects were sustained over the 24-month follow-up period.
      There were some statistically significant differences between the 2 groups
      relating to secondary end points, Roland-Morris disability questionnaire, and in
      the MOS 36-Item Short-Form Health Survey the "physical functioning" dimension and
      the "physical component summary." CONCLUSION: Both groups showed long-term
      improvements in pain and disability scores, with only minor statistically
      significant differences between the 2 groups. The minor outcome difference in
      favor of the group-based multidisciplinary rehabilitation program is hardly of
      clinical interest for individual patients.

PMID- 20147879
TI  - Disproportionate body lengths correlate with idiopathic-type curvature in the
      curveback guppy.
AB  - STUDY DESIGN: A comparative allometric study of body lengths in an animal model
      for human idiopathic-type scoliosis. OBJECTIVE: To compare body length variation
      among adult curved and noncurved curveback female guppies. SUMMARY OF BACKGROUND
      DATA: Tallness and/or abnormal anthropometric parameters have been correlated to
      idiopathic-type scoliosis (IS) in numerous studies. Heritable curvature in
      curveback has demonstrated morphologic and developmental similarities to human
      IS. Because control of body length in the guppy is heritable and variable, we
      investigated whether length might also be correlated to curvature in the
      curveback population. METHODS: Component body lengths were measured from digital
      photographs for 321 (246 curved and 75 noncurved) females. Sources of
      experimental variation were omitted by only measuring 2-dimensional curves in
      mature females all from the same pedigree, and raised under controlled conditions
      of diet and environment. Body length was divided into 2 component parts
      (precaudal and caudal). Body lengths were tested statistically for correlation to
      curvature and curve magnitude. RESULTS: Although absolute length does not
      correlate to curvature, this survey of length in the curveback model reveals 2
      important similarities to anthropometric studies of IS: that there are
      disproportionate body lengths among females with curvature, and the suggestion of
      an underlying growth abnormality among curved individuals. CONCLUSION: In order
      to better characterize the relationship between growth, length disproportion, and
      curvature in the guppy, further studies are warranted. However, this inquiry
      further supports the usefulness of curveback as a model for understanding the
      basic biology of idiopathic-type scoliosis and encourages study of growth-related
      factors.

PMID- 20147880
TI  - Decrease in postural sway and trunk stiffness during cognitive dual-task in
      nonspecific chronic low back pain patients, performance compared to healthy
      control subjects.
AB  - STUDY DESIGN: A 2-group experimental design. OBJECTIVE: To investigate the effect
      of a cognitive dual-task on postural sway of pelvis and trunk during unstable
      sitting in nonspecific chronic patients with low back pain (CLBP) compared to
      healthy control subjects. SUMMARY OF BACKGROUND DATA: Higher cognitive systems as
      well as sensory processes contribute to postural control. An increase in postural
      sway due to a cognitive dual task could mean more need of cognitive systems to
      control balance. METHODS: A total of 21 CLBP patients and 21 control subjects
      were included based on detailed clinical criteria. Every subject was submitted to
      2 postural control tests in an unstable sitting position (easy test position: 2
      feet on the ground and difficult test position: 1 foot lifted). Both tests were
      performed with and without cognitive dual-task. A 3-dimensional motion analysis
      system was used measure angular displacement of trunk and pelvis in the 3
      cardinal planes. RESULTS: In the most difficult balance position, postural sway
      increases in the control group when the cognitive dual-task is added, for 50% of
      the variables the increase is significant (P between 0.02 and 0.05). On the
      contrary, postural sway decreases, not significantly, in the CLBP group when the
      dual-task is added. These findings are the same for trunk as for pelvis
      deviations. The Pearson correlation coefficient between trunk and pelvis movement
      from the CLBP group are lower for all 3 movement directions in the dual-task
      condition (r between 0.441 and 0.988) compared to the single task condition (r
      between 0.982 and 0.995). CONCLUSION: In nonspecific CLBP patients, a cognitive
      dual-task reduces both postural sway and trunk stiffness due to the distracting
      effect of the dual-task. This effect is only visible when the balance task is
      difficult.

PMID- 20147881
TI  - Validation of sodium magnetic resonance imaging of intervertebral disc.
AB  - STUDY DESIGN: This study demonstrated the diagnostic potential of sodium (Na)
      magnetic resonance imaging (MRI) for noninvasive quantification of proteoglycan
      (PG) in the intervertebral discs. OBJECTIVE: To determine the existence of a
      linear correlation between intervertebral disc [Na] measured from sodium MRI and
      [PG] measurement from DMMB assay. SUMMARY OF BACKGROUND DATA: Previous studies
      have shown the possibility of quantifying Na in vivo using sodium MRI, however,
      none has shown a direct linear correlation between Na measured from sodium MRI
      and in the invertebral discs. METHODS: Three-dimensional sodium MRI images of
      bovine discs were acquired and converted into [Na] maps. Samples were
      systematically removed from the discs for DMMB assay. The removal locations were
      photographically recorded and applied to the [Na] maps to extract the [Na]
      measurements for comparison. In vivo sodium MRI scans were also carried out on a
      pair of symptomatic and asymptomatic subjects. RESULTS: The linear regression fit
      of [Na] versus [PG] data yielded a significant linear correlation coefficient of
      0.71. The in vivo sodium MRI image of the symptomatic subject showed significant
      [Na] decrease when compared to that of the asymptomatic subject. CONCLUSION:
      Specificity of sodium MRI for PG in the intervertebral discs makes it a promising
      diagnostic tool for the earlier phase of disc degeneration.

PMID- 20147882
TI  - Reliability and validity of the finnish version of the neck disability index and
      the modified neck pain and disability scale.
AB  - STUDY DESIGN: Translation and psychometric testing. OBJECTIVE: To cross
      culturally adapt the Neck Disability Index (NDI) to the Finnish language and to
      assess the reliability and validity of the Finnish version of the Neck Disability
      Index (NDI-FI) and the modified Neck Pain and Disability Scale (mNPDS-FI) in
      Finnish patients with neck pain. SUMMARY OF BACKGROUND DATA: Although largely
      used, no previous reports exist on the translation process or the testing of the
      psychometric properties of the Finnish version of the NDI or the mNPDS used in
      Finland. METHODS: The translation of the questionnaire from English into Finnish
      was done in accordance with the published guidelines. A total of 101 patients
      with neck pain participated in the study. The reliability of the questionnaires
      was tested using a test-retest procedure at 2-week intervals. Further
      psychometric testing was done by assessing the construct validity and internal
      consistency of the questionnaires. RESULTS: Test-retest reliability (intraclass
      correlation coefficients) was excellent for the NDI-FI (0.94) and mNPDS-FI
      (0.91). Factor analysis identified 1 factor for the NDI-FI and 3 factors for the
      mNPDS-FI; pain intensity, work ability, and activities of daily living. The
      internal consistency value (Cronbach alpha) for the NDI-FI was 0.85, and 0.84,
      0.83, and 0.82, respectively, for the 3 factors of the mNPDS-FI. The correlation
      between neck pain and the NDI-FI was 0.58 (P < 0.001) and 0.72 for the mNPDS-FI
      (P < 0.001). A statistically significant linear relationship was observed between
      self-estimated coping and the outcomes of the NDI-FI and the mNPDS-FI.
      CONCLUSION: The NDI-FI and the mNPDS-FI are reliable, valid instruments for
      assessing disability among Finnish patients with neck pain.

PMID- 20147883
TI  - Return to work and social participation: does type of organ transplantation
      matter?
AB  - BACKGROUND: Return to work and social participation are objective parameters to
      evaluate the success of transplantation. Existing reports never compared return
      to work rates between different organ transplant groups, few European studies
      were published, and information on patients having a volunteer job or being an
      active club member is scarce. These outcomes have never been compared with the
      general population. METHODS: In a cross-sectional sample of 281 kidney, heart,
      liver, and lung transplant patients, we assessed self-reported return to work
      (i.e., having a paid job) and social participation (i.e., having a volunteer job
      or being an active member of a club). These data were compared with the general
      population. We also explored possible correlates of return to work (multivariable
      regression analysis). RESULTS: Kidney transplant patients had the highest
      employment rate (58.6%), followed by heart (43.6%), liver (37.5%), and lung
      transplant patients (28.1%). Except for kidney patients, these numbers are lower
      than the 62% population's employment rate. Return to work was more likely if the
      transplanted organ was other than lung, with younger age at time of
      transplantation, being male, being married, having a positive perception of one's
      capability to work, and having worked until at least 1 year before transplant.
      Volunteer work was similar to the general population (17.4% vs. 21.5%), although
      less patients were an active club member (28.5% vs. 61%). CONCLUSION: Obtaining a
      paid or voluntary job posttransplantation is possible and should be strongly
      recommended by transplant professionals as a meaningful way to contribute to the
      society.

PMID- 20147884
TI  - Transcriptome changes of chronic tubulointerstitial damage in early kidney
      transplantation.
AB  - BACKGROUND: Tubulointerstitial damage (TID) is a key feature of chronic kidney
      transplant failure; however, the associated gene expression changes are poorly
      defined. METHODS: This pilot study used RNA from 59 protocol kidney transplant
      biopsies at implantation, 1, 3, and 12 months (n=18 patients), processed into
      cDNA and hybridized to 8K human cDNA microarrays. Gene expression was correlated
      with graft histology categorized by the Banff schema. RESULTS: Gene and pathway
      expression were differentially activated according to the time after
      transplantation. Immune pathway activity peaked at 1 month, fibrotic expression
      at 3 months, wound healing-remodelling and cell proliferation-repair processes
      were activated between 3 and 12 months, whereas macrophage-related gene
      expression occurred late by 12 months. Forty percent of genes and 50% pathways
      initially activated persisted to 3 months. Biopsies with TID displayed 262
      differentially expressed genes (P<0.001, B>2 compared with implantation),
      dominated by upregulated fibrogenic and immune-related genes reflecting unique
      immune (10% to 15% of genes) and fibrotic (15% vs. 4% in normal) pathway
      activation. Profibrotic genes were expressed before interstitial fibrosis was
      observed by sequential microscopic analysis. Kidneys progressing to TID by 3
      months demonstrated 30 unique genes (B>1, P<0.05) versus nonprogressors with 95
      genes (B>1, P<0.009). Fourteen of these progressor genes also occurred in the top
      decile from an independent validation set. CONCLUSIONS: Allografts display
      predictable immune and fibrotic gene expression profiles, with patterns of
      expression gradually varying by time after transplantation. The pathology
      reflects differential activation of intrinsic pathways. Gene expression predated
      histologic damage, suggesting its possible use in early diagnostic testing.

PMID- 20147885
TI  - The 2009 Lindau Nobel Laureate meeting: Martin Chalfie, Chemistry 2008.
AB  - American Biologist Martin Chalfie shared the 2008 Nobel Prize in Chemistry with
      Roger Tsien and Osamu Shimomura for their discovery and development of the Green
      Fluorescent Protein (GFP). Martin Chalfie was born in Chicago in 1947 and grew up
      in Skokie Illinois. Although he had an interest in science from a young age-
      learning the names of the planets and reading books about dinosaurs--his journey
      to a career in biological science was circuitous. In high school, Chalfie enjoyed
      his AP Chemistry course, but his other science courses did not make much of an
      impression on him, and he began his undergraduate studies at Harvard uncertain of
      what he wanted to study. Eventually he did choose to major in Biochemistry, and
      during the summer between his sophomore and junior years, he joined Klaus Weber's
      lab and began his first real research project, studying the active site of the
      enzyme aspartate transcarbamylase. Unfortunately, none of the experiments he
      performed in Weber's lab worked, and Chalfie came to the conclusion that research
      was not for him. Following graduation in 1969, he was hired as a teacher Hamden
      Hall Country Day School in Connecticut where he taught high school chemistry,
      algebra, and social sciences for 2 years. After his first year of teaching, he
      decided to give research another try. He took a summer job in Jose Zadunaisky's
      lab at Yale, studying chloride transport in the frog retina. Chalfie enjoyed this
      experience a great deal, and having gained confidence in his own scientific
      abilities, he applied to graduate school at Harvard, where he joined the
      Physiology department in 1972 and studied norepinephrine synthesis and secretion
      under Bob Pearlman. His interest in working on C. elegans led him to post doc
      with Sydney Brenner, at the Medical Research Council Laboratory of Molecular
      Biology in Cambridge, England. In 1982 he was offered position at Columbia
      University. When Chalfie first heard about GFP at a research seminar given by
      Paul Brehm in 1989, his lab was studying genes involved in the development and
      function of touch-sensitive cells in C. elegans. He immediately became very
      excited about the idea of expressing the fluorescent protein in the nematode,
      hoping to figure out where the genes were expressed in the live organism. At the
      time, all methods of examining localization, such as antibody staining or in situ
      hybridization, required fixation of the tissue or cells, revealing the location
      of proteins only at fixed points in time. In September 1992, after obtaining GFP
      DNA from Douglas Prasher, Chalfie asked his rotation student, Ghia Euskirchen to
      express GFP in E. coli, unaware that several other labs were also trying to
      express the protein, without success. Chalfie and Euskirchen used PCR to amplify
      only the coding sequence of GFP, which they placed in an expression vector and
      expressed in E.coli. Because of her engineering background, Euskirchen knew that
      the microscope in the Chalfie lab was not good enough to use for this type of
      experiment, so she captured images of green bacteria using the microscope from
      her former engineering lab. This work demonstrated that GFP fluorescence requires
      no component other than GFP itself. In fact, the difficulty that other labs had
      encountered stemmed from their use of restriction enzyme digestions for
      subcloning, which brought along an extra sequence that prevented GFP's
      fluorescent expression. Following Euskirchen's successful expression in E. coli,
      Chalfie's technician Yuan Tu went on to express GFP in C. elegans, and Chalfie
      published the findings in Science in 1994. Through the study of C. elegans and
      GFP, Chalfie feels there is an important lesson to be learned about the
      importance basic research. Though there has been a recent push for clinically
      relevant or patent-producing (translational) research, Chalfie warns that taking
      this approach alone is a mistake, given how "woefully little" we know about
      biology. He points out the vast expanse of the unknowns in biology, noting that
      important discoveries such as GFP are very frequently made through basic research
      using a diverse set of model organisms. Indeed, the study of GFP bioluminescence
      did not originally have a direct application to human health. Our understanding
      of it, however, has led to a wide array of clinically-relevant discoveries and
      developments. Chalfie believes we should not limit ourselves: "We should be a
      little freer and investigate things in different directions, and be a little bit
      awed by what we're going to find."

PMID- 20147886
TI  - Age and comorbidity may explain the paradoxical association of an early dialysis
      start with poor survival.
AB  - Starting patients on dialysis early has been increasing in incidence in several
      countries. However, some studies have questioned its utility, finding a counter
      intuitive effect of increased mortality when dialysis was started at a higher
      estimated glomerular filtration rate (eGFR). To examine this issue in more detail
      we measured mortality hazard ratios associated with Modification of Diet in Renal
      Disease eGFR at dialysis initiation for 11,685 patients from the French REIN
      Registry, with sequential adjustment for a number of covariates. The eGFR was
      analyzed both quantitatively by 5-ml/min per 1.73 m(2) increments and by demi
      decile (i.e., 5 percentiles of the distribution); the 15th demi-decile, including
      values around 10 ml/min per 1.73 m(2), was our reference point. The patients more
      likely to begin dialysis at a higher eGFR were older male patients; had diabetes,
      cardiovascular diseases, or low body mass index and level of albuminemia; or were
      started with peritoneal dialysis. During a median follow-up of 21.9 months, 3945
      patients died. The 2-year crude survival decreased from 79 to 46%, with
      increasing eGFR from less than 5 to over 20 ml/min per 1.73 m(2). Each 5
      ml/min/1.73 m(2) increase in eGFR was associated with a 40% increase in crude
      mortality risk, which weakened to 9%, but remained statistically significant
      after adjusting for the above covariates. Analysis by demi-decile showed only the
      highest to be at significantly higher risk. Hence we found that age and patient
      condition strongly determine the decision to start dialysis and may explain most
      of the inverse association between eGFR and survival.

PMID- 20147887
TI  - Predictive value of baseline serum vascular endothelial growth factor and
      neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients
      receiving sunitinib.
AB  - To identify factors that might predict response to sunitinib in patients with
      renal cell carcinoma, we measured serum vascular endothelial growth factor (VEGF)
      and neutrophil gelatinase-associated lipocalin (NGAL) levels. A total of 85
      patients were selected and, using the Motzer classification, 46 were assigned to
      the good- and 38 to the intermediate-risk groups. With univariate Cox analysis,
      both baseline serum VEGF and NGAL titers, determined by enzyme-linked
      immunosorbent assay, significantly predicted progression-free survival. For each
      biomarker, a threshold value was identified, which proved useful to classify
      patients into groups having titers above or below the thresholds. We then
      stratified patients according to the two dichotomous variables into good-,
      intermediate-, and poor-risk groups, and found significantly different
      progression-free survival rates ranging from 3.5 to 11.6 months. Both VEGF and
      NGAL maintained their predictive significance at bivariate analysis. Our study
      shows that serum levels of VEGF and NGAL are significant predictors of
      progression-free survival in patients with renal cell carcinoma treated with
      sunitinib.

PMID- 20147888
TI  - Afferent mechanisms of sodium retention in cirrhosis and hepatorenal syndrome.
AB  - Cirrhosis induces extra-cellular fluid volume expansion, which when the disease
      is advanced can be severe and poorly responsive to therapy. Prevention and/or
      effective therapy for cirrhotic edema requires understanding the stimulus that
      initiates and maintains sodium retention. Despite much study, this stimulus
      remains unknown. Work over the last several years has shown that signals
      originating in the liver can influence a variety of systemic functions, including
      extra-cellular fluid volume control. We review work on the afferent mechanisms
      triggering sodium retention in cirrhosis and suggest that the data are most
      consistent with the existence of a sensor in the hepatic circulation that
      contributes to normal extra-cellular fluid volume control (that is, a 'volume'
      sensor) and that in cirrhosis, the sensor is pathologically activated by the
      hepatic circulatory abnormalities caused by the disease. Detailed analysis of the
      hepatic circulation in normal conditions and cirrhosis is needed.

PMID- 20147889
TI  - Amygdala transcriptome and cellular mechanisms underlying stress-enhanced fear
      learning in a rat model of posttraumatic stress disorder.
AB  - Severe stress or trauma can cause permanent changes in brain circuitry, leading
      to dysregulation of fear responses and the development of posttraumatic stress
      disorder (PTSD). To date, little is known about the molecular mechanisms
      underlying stress-induced long-term plasticity in fear circuits. We addressed
      this question by using global gene expression profiling in an animal model of
      PTSD, stress-enhanced fear learning (SEFL). A total of 15 footshocks were used to
      induce SEFL and the volatile anesthetic isoflurane was used to suppress the
      behavioral effects of stress. Gene expression in lateral/basolateral amygdala was
      measured using microarrays at 3 weeks after the exposure to different
      combinations of shock and isoflurane. Shock produced robust effects on amygdalar
      transcriptome and isoflurane blocked or reversed many of the stress-induced
      changes. We used a modular approach to molecular profiles of shock and isoflurane
      and built a network of regulated genes, functional categories, and cell types
      that represent a mechanistic foundation of perturbation-induced plasticity in the
      amygdala. This analysis partitioned perturbation-induced changes in gene
      expression into neuron- and astrocyte-specific changes, highlighting a previously
      underappreciated role of astroglia in amygdalar plasticity. Many neuron-enriched
      genes were highly correlated with astrocyte-enriched genes, suggesting
      coordinated transcriptional responses to environmental challenges in these cell
      types. Several individual genes were validated using RT-PCR and behavioral
      pharmacology. This study is the first to propose specific cellular and molecular
      mechanisms underlying SEFL, an animal model of PTSD, and to nominate novel
      molecular and cellular targets with potential for therapeutic intervention in
      PTSD, including glycine and neuropeptide systems, chromatin remodeling, and
      gliotransmission.

PMID- 20147890
TI  - Confirmation and generalization of an alcohol-dependence locus on chromosome 10q.
AB  - Several genome scans on alcohol dependence (AD) and AD-related traits have been
      published. In this article, we present the results of a genome-wide linkage scan
      on AD and several related traits in 322 European-American (EA) families, and
      results of additional analysis in 335 African-American (AA) families that were
      the subject of a previous report. All families were initially ascertained for
      cocaine and/or opioid dependence. Non-parametric linkage analysis in the EA
      sample revealed suggestive linkages on chromosomes 7 (LOD=2.1 at 82.8 cM,
      p=0.0009) and 10 (LOD=3.0 at 137.7 cM, p=0.0001). The chromosome 10 linkage peak
      is 20 cM distal from a genome-wide significant linkage peak we observed
      previously in the AA sample. Parametric linkage analysis on chromosome 10
      (assuming a recessive model, 80% penetrance, disease allele frequency=0.3)
      resulted in LOD scores of 2.7 at 136.7 cM and 1.9 at 121.7 cM in the EA and AA
      samples, respectively, with a combined sample genome-wide significant LOD score
      of 4.1 at 131.7 cM. To reduce heterogeneity of the AD phenotype, we also assessed
      linkage of chromosome 10 markers with the presence of alcohol withdrawal
      symptoms, one of the seven components of the DSM-IV diagnosis of AD. Suggestive
      evidence for linkage was observed in both populations with only 5 cM separating
      the location of the peak LOD scores despite a loss of power due to a smaller
      number of families informative for this trait. Results of our study confirm a
      chromosome 10 risk locus for AD in two genetically distinct populations and
      suggest that this locus may correspond more precisely to a specific component of
      the disorder.

PMID- 20147891
TI  - Childhood stress, serotonin transporter gene and brain structures in major
      depression.
AB  - The underlying neurobiology of major depression (MD) is likely to represent an
      interaction between genetic susceptibility and environmental factors such as
      stress. We investigated, in a multimodal high-resolution magnetic resonance
      imaging (MRI) genetic study, whether reduced hippocampal volumes and other brain
      alterations are associated with the tri-allelic polymorphism of the serotonin
      transporter and childhood stress in patients with MD and healthy subjects.
      Patients with MD and healthy participants were investigated using high-resolution
      MRI and genotyping for serotonin transporter polymorphism in the promoter region
      of the serotonin transporter gene (SLC6A4, 5-HTTLPR). Region of interest analysis
      of the hippocampus, whole-brain voxel-based morphometry (VBM), and assessment of
      childhood stress were carried out. Patients carrying the risk S-allele developed
      smaller hippocampal volumes when they had a history of emotional neglect compared
      with patients who only had one risk factor (environmental or genetic). In
      patients, childhood stress also predicted further hippocampal white matter
      alterations independently from the genotype. Moreover, the left prefrontal cortex
      was smaller in patients, whereby childhood stress resulted in larger prefrontal
      volumes in those subjects carrying the non-risk L-allele, suggesting preventive
      effects. The findings indicate that subjects with both environmental and genetic
      risk factors are susceptible to stress-related hippocampal changes. Structural
      brain changes due to stress represent part of the mechanism by which the illness
      risk and outcome might be genetically mediated.

PMID- 20147892
TI  - Convergent evidence that choline acetyltransferase gene variation is associated
      with prospective smoking cessation and nicotine dependence.
AB  - The ability to quit smoking is heritable, yet few genetic studies have
      investigated prospective smoking cessation. We conducted a systems-based genetic
      association analysis in a sample of 472 treatment-seeking smokers of European
      ancestry after 8 weeks of transdermal nicotine therapy for smoking cessation. The
      genotyping panel included 169 single-nucleotide polymorphisms (SNPs) in 7
      nicotinic acetylcholine receptor subunit genes and 4 genes in the endogenous
      cholinergic system. The primary outcome was smoking cessation (biochemically
      confirmed) at the end of treatment. SNPs clustered in the choline
      acetyltransferase (ChAT) gene were individually identified as nominally
      significant, and a 5-SNP haplotype (block 6) in ChAT was found to be
      significantly associated with quitting success. Single SNPs in ChAT haplotype
      block 2 were also associated with pretreatment levels of nicotine dependence in
      this cohort. To replicate associations of SNPs in haplotype blocks 2 and 6 of
      ChAT with nicotine dependence in a non-treatment-seeking cohort, we used data
      from an independent community-based sample of 629 smokers representing 200
      families of European ancestry. Significant SNP and haplotype associations were
      identified for multiple measures of nicotine dependence. Although the effect
      sizes in both cohorts are modest, converging data across cohorts and phenotypes
      suggest that ChAT may be involved in nicotine dependence and ability to quit
      smoking. Additional sequencing and characterization of ChAT may reveal functional
      variants that contribute to nicotine dependence and smoking cessation.

PMID- 20147893
TI  - Enhancement of attentional performance by selective stimulation of alpha4beta2(*)
      nAChRs: underlying cholinergic mechanisms.
AB  - Impairments in attention are a major component of the cognitive symptoms of
      neuropsychiatric and neurodegenerative disorders. Using an operant sustained
      attention task (SAT), including a distractor condition (dSAT), we assessed the
      putative pro-attentional effects of the selective alpha4beta2(*) nicotinic
      acetylcholine receptor (nAChR) agonist S 38232 in comparison with the non
      selective agonist nicotine. Neither drug benefited SAT performance. However, in
      interaction with the increased task demands implemented by distractor
      presentation, the selective agonist, but not nicotine, enhanced the detection of
      signals during the post-distractor recovery period. This effect is consistent
      with the hypothesis that second-long increases in cholinergic activity
      ('transients') mediate the detection of cues and that nAChR agonists augment such
      transients. Electrochemical recordings of prefrontal cholinergic transients
      evoked by S 38232 and nicotine indicated that the alpha4beta2(*) nAChR agonist
      evoked cholinergic transients that were characterized by a faster rise time and
      more rapid decay than those evoked by nicotine. Blockade of the alpha7 nAChR
      'sharpens' nicotine-evoked transients; therefore, we determined the effects of co
      administration of nicotine and the alpha7 nAChR antagonist methyllycaconitine on
      dSAT performance. Compared with vehicle and nicotine alone, this combined
      treatment significantly enhanced the detection of signals. These results indicate
      that compared with nicotine, alpha4beta2(*) nAChR agonists significantly enhance
      attentional performance and that the dSAT represents a useful behavioral
      screening tool. The combined behavioral and electrochemical evidence supports the
      hypothesis that nAChR agonist-evoked cholinergic transients, which are
      characterized by rapid rise time and fast decay, predict robust drug-induced
      enhancement of attentional performance.

PMID- 20147894
TI  - Segmented filamentous bacteria take the stage.
AB  - Commensal bacteria are crucial for maturation and function of the mucosal immune
      system. However, the mechanisms of these interactions are poorly understood. In
      addition, the role of the composition of the microbiota and the importance of
      individual species in this community in stimulating different types of immunity
      are major unanswered questions. We recently showed that the balance between two
      major effector T cell populations in the intestine, IL-17(+) Th17 cells and
      Foxp3(+) Tregs, requires signals from commensal bacteria and is dependent on the
      composition of the intestinal microbiota. Comparison of microbiota from Th17 cell
      deficient and Th17 cell-sufficient mice identified segmented filamentous bacteria
      (SFB) as capable of specifically inducing Th17 cells in the gut. SFB represent
      the first example of a commensal species that can skew the mucosal effector T
      cell balance and thus affect the immune fitness of the individual.

PMID- 20147895
TI  - HIV-1 sexual transmission: early events of HIV-1 infection of human cervico
      vaginal tissue in an optimized ex vivo model.
AB  - Infection and dissemination of human immunodeficiency virus (HIV)-1 through the
      female body after vaginal intercourse depends on the activation/differentiation
      status of mucosal CD4 T cells. In this study, we investigated this status and the
      susceptibility to HIV-1 infection of human cervico-vaginal tissue ex vivo. We
      found that virtually all T cells are of the effector memory phenotype with broad
      CC chemokine receptor 5 (CCR5) expression. As it does in vivo, human cervico
      vaginal tissue ex vivo preferentially supports the productive infection of R5 HIV
      1 rather than that of X4 HIV-1 in spite of the broad expression of CXC chemokine
      receptor 4 (CXCR4). X4 HIV-1 replicated only in the few tissues that were
      enriched in CD27(+)CD28(+) effector memory CD4 T cells. Productive infection of
      R5 HIV-1 occurred preferentially in activated CD38(+)CD4 T cells and was followed
      by a similar activation of HIV-1-uninfected (bystander) CD4 T cells that may
      amplify viral infection. These results provide new insights into the dependence
      of HIV-1 infection and dissemination on the activation/differentiation of cervico
      vaginal lymphocytes.

PMID- 20147897
TI  - Applying physiological and biochemical concepts to optimize biological drug
      development.
AB  - Posology--the science of dose and regimen--is a critical part of drug
      development. It is concerned with ensuring that patients experience significant
      clinical benefit without intolerable adverse effects. It has become apparent, in
      the case of certain biologics, that one can directly quantitate occupancy or
      target capture and relate these to clinical responses. With mathematical models
      that integrate binding concepts with clinical effects, potential posologies can
      be quickly explored through simulation, thereby liberating research teams from
      the traditional constraints and simultaneously stimulating innovation.

PMID- 20147896
TI  - A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug
      interactions with the mixed inhibitor/inducer tipranavir/ritonavir.
AB  - The effects of tipranavir/ritonavir (TPV/r) on hepatic and intestinal P
      glycoprotein (P-gp) and cytochrome P450 (CYP) enzyme activity were evaluated in
      23 volunteers. The subjects received oral (p.o.) caffeine, warfarin + vitamin K,
      omeprazole, dextromethorphan, and midazolam and digoxin (p.o. and intravenous
      (i.v.)) at baseline, during the first three doses of TPV/r (500 mg/200 mg
      b.i.d.), and at steady state. Plasma area under the curve (AUC)(0-infinity) and
      urinary metabolite ratios were used for quantification of protein activities. A
      single dose of TPV/r had no effect on the activity of CYP1A2 and CYP2C9; it
      weakly inhibited CYP2C19 and P-gp; and it potently inhibited CYP2D6 and CYP3A.
      Multiple dosing produced weak induction of CYP1A2, moderate induction of CYP2C19,
      potent induction of intestinal P-gp, and potent inhibition of CYP2D6 and CYP3A,
      with no significant effects on CYP2C9 and hepatic P-gp. Several P450/transporter
      single-nucleotide polymorphisms correlated with the baseline phenotype but not
      with the extent of inhibition or induction. Although mixed induction and
      inhibition are present, this approach offers an understanding of drug interaction
      mechanisms and ultimately assists in optimizing the clinical use of TPV/r.

PMID- 20147898
TI  - Inflammation: planning for a source of pharmacokinetic/pharmacodynamic
      variability in translational studies.
AB  - The impact of inflammation on variability in the pharmacokinetics (PK) and
      pharmacodynamics (PD) of drugs should be considered in the design, analysis, and
      interpretation of clinical pharmacology studies. Data suggest that the metabolism
      and transport of drugs, as well as the expression of receptors, may change in the
      presence of inflammation. The clinical implications of these changes are not
      straightforward; they may vary depending on whether the inflammation is active or
      controlled and may change with time and successful treatment of the inflammation.

PMID- 20147899
TI  - Inflammation and cancer: causes and consequences.
AB  - The link between chronic inflammation and increased risk of developing some
      cancers is well established. The molecular mechanisms that underlie this process
      (cause) as well as the chronic inflammation that accompanies cancer (consequence)
      continue to be elucidated. Cancer-associated inflammation has effects on the
      ability of cancers to metastasize, on the clinical manifestations of cancer, and
      on the ability of the patient to tolerate anticancer therapy. The identification
      of biomarkers of cancer-associated inflammation will assist in identifying
      patients at risk of its consequences.

PMID- 20147900
TI  - Arthropod relationships revealed by phylogenomic analysis of nuclear protein
      coding sequences.
AB  - The remarkable antiquity, diversity and ecological significance of arthropods
      have inspired numerous attempts to resolve their deep phylogenetic history, but
      the results of two decades of intensive molecular phylogenetics have been mixed.
      The discovery that terrestrial insects (Hexapoda) are more closely related to
      aquatic Crustacea than to the terrestrial centipedes and millipedes (Myriapoda)
      was an early, if exceptional, success. More typically, analyses based on limited
      samples of taxa and genes have generated results that are inconsistent, weakly
      supported and highly sensitive to analytical conditions. Here we present strongly
      supported results from likelihood, Bayesian and parsimony analyses of over 41
      kilobases of aligned DNA sequence from 62 single-copy nuclear protein-coding
      genes from 75 arthropod species. These species represent every major arthropod
      lineage, plus five species of tardigrades and onychophorans as outgroups. Our
      results strongly support Pancrustacea (Hexapoda plus Crustacea) but also strongly
      favour the traditional morphology-based Mandibulata (Myriapoda plus Pancrustacea)
      over the molecule-based Paradoxopoda (Myriapoda plus Chelicerata). In addition to
      Hexapoda, Pancrustacea includes three major extant lineages of 'crustaceans',
      each spanning a significant range of morphological disparity. These are
      Oligostraca (ostracods, mystacocarids, branchiurans and pentastomids),
      Vericrustacea (malacostracans, thecostracans, copepods and branchiopods) and
      Xenocarida (cephalocarids and remipedes). Finally, within Pancrustacea we
      identify Xenocarida as the long-sought sister group to the Hexapoda, a result
      confirming that 'crustaceans' are not monophyletic. These results provide a
      statistically well-supported phylogenetic framework for the largest animal phylum
      and represent a step towards ending the often-heated, century-long debate on
      arthropod relationships.

PMID- 20147904
TI  - Just a minute.

PMID- 20147905
TI  - Mouthwash controversies.

PMID- 20147901
TI  - Microtubules and resistance to tubulin-binding agents.
AB  - Microtubules are dynamic structures composed of alpha-beta-tubulin heterodimers
      that are essential in cell division and are important targets for cancer drugs.
      Mutations in beta-tubulin that affect microtubule polymer mass and/or drug
      binding are associated with resistance to tubulin-binding agents such as
      paclitaxel. The aberrant expression of specific beta-tubulin isotypes, in
      particular betaIII-tubulin, or of microtubule-regulating proteins is important
      clinically in tumour aggressiveness and resistance to chemotherapy. In addition,
      changes in actin regulation can also mediate resistance to tubulin-binding
      agents. Understanding the molecular mechanisms that mediate resistance to tubulin
      binding agents will be vital to improve the efficacy of these agents.

PMID- 20147902
TI  - Breast and prostate cancer: more similar than different.
AB  - Breast cancer and prostate cancer are the two most common invasive cancers in
      women and men, respectively. Although these cancers arise in organs that are
      different in terms of anatomy and physiological function both organs require
      gonadal steroids for their development, and tumours that arise from them are
      typically hormone-dependent and have remarkable underlying biological
      similarities. Many of the recent advances in understanding the pathophysiology of
      breast and prostate cancers have paved the way for new treatment strategies. In
      this Opinion article we discuss some key issues common to breast and prostate
      cancer and how new insights into these cancers could improve patient outcomes.

PMID- 20147906
TI  - Hypertension screening.

PMID- 20147907
TI  - Cavalier attitude.

PMID- 20147908
TI  - Spiralling costs.

PMID- 20147909
TI  - Familiar forceps.

PMID- 20147910
TI  - An unviable approach.

PMID- 20147911
TI  - The NHS reality.

PMID- 20147912
TI  - Internet caution.

PMID- 20147921
TI  - Study highlights fluoridated toothpaste use in children.

PMID- 20147923
TI  - Evaluation of dental practitioners with special interest in minor oral surgery.
AB  - This paper reports an evaluation of dental practitioners with special interest
      (DPwSI) in minor oral surgery (MOS). OBJECTIVES: To: i) audit the appropriateness
      of referrals to a DPwSI-MOS service, ii) determine its cost-effectiveness, iii)
      gather the views of patients who had been treated, and iv) assess the referring
      dentists' views. METHODS: Analysis of management information, telephone
      interviews with patients, postal questionnaire survey of referring dentist.
      RESULTS: Of 83 referrals received, 51 (five for consultation and 46 for
      extractions) were seen by a DPwSI. The average waiting time between the referral
      and the treatment dates was 36 days. The cost of treating 51 cases was pound
      8,020, compared to pound 43,608 under secondary care, a difference of pound
      35,588 and a projected annual difference of pound 142,352. Eighteen patients were
      interviewed after attending for treatment. Most reported that they were seen
      within two weeks (ten, 57%) and four weeks (five, 28%) from the time they were
      referred. The majority (15, 83%) rated the service as good to excellent. Of the
      questionnaires mailed to 90 referring dentists, 45 (50%) were returned. Of the 40
      (90%) dentists who reported being aware of the DPwSI-MOS, 24 (60%) reported
      having used the service. CONCLUSIONS: This pilot has demonstrated that the
      provision of MOS in the primary care setting by DPwSIs can provide a good service
      for patients, potentially improve access for patients, support patient management
      for referring dentists and reduce costs for the PCT.

PMID- 20147924
TI  - Autotransplantation of premolars.
AB  - Autotransplantation is a reliable treatment option for the replacement of missing
      teeth; however, there is a wide variation in reported survival rates. The purpose
      of this study was to evaluate the success and survival rate of premolar
      autotransplantation and to underline the importance of autotransplantation in the
      treatment of missing teeth. We present the treatment and follow-up of 63 premolar
      autotransplants in 44 patients. After transplantation under local anaesthesia,
      radiological and clinical follow-up showed a survival rate of 100%, ie all
      premolars were still functional. We conclude that autotransplantation of
      premolars is a reliable treatment method especially for agenesis. It is not
      difficult to perform and is aesthetically superior and more cost-effective than
      other treatments, especially when orthodontic alignment is necessary.

PMID- 20147929
TI  - Summary of: Antibiotic prophylaxis in oral healthcare - the agreement between
      Swedish recommendations and evidence.
AB  - Background Almost all (17/20) Swedish counties have pharmaceutical committees
      that establish recommendations for the use of antibiotic prophylaxis in oral
      healthcare.Objective To evaluate the evidence for the use of antibiotic
      prophylaxis in oral healthcare and the agreement between Swedish recommendations
      and evidence.Material and methods We conducted a systematic literature search in
      PubMed and the Cochrane Controlled Trials Register. The MeSH terms 'antibiotic
      prophylaxis' and 'dentistry' were used in the database search. Abstracts were
      reviewed according to specific inclusion and exclusion criteria. A total of 186
      articles were read in full text by the four authors independently. Data
      extraction and interpretation of data was carried out using a pre-defined
      protocol. In the end, one case-control study was included for evaluation of
      evidence.Results The case-control study included patients with specific cardiac
      conditions. The study reported a 49% protective efficacy (odds ratio: 0.51) of
      antibiotic prophylaxis for first-time episodes of endocarditis within 30 days of
      procedure. This result was not statistically significant. The quality of the
      evidence was low. No studies were evaluated on patients with other medical
      conditions. The recommendations included several cardiac and other medical
      conditions for which there is a lack of evidence or no evidence to support the
      use of antibiotic prophylaxis.Conclusions There is a lack of evidence to support
      the use of antibiotic prophylaxis. To avoid the risk of adverse events from
      antibiotics and the risk of developing resistant bacterial strains, the use of
      antibiotic prophylaxis should be minimised and recommendations in Sweden should
      be revised to be more evidence-based.

PMID- 20147930
TI  - Summary of: Modelling workforce skill-mix: how can dental professionals meet the
      needs and demands of older people in England?
AB  - Background There is an urgent need to consider the skill-mix of the dental team
      to meet the oral health needs and demands of the population in general, and older
      people in particular. As people live longer and retain their teeth there will be
      a progressive change in both the volume and type of dental care required, and the
      demand for care. Operational research modelling provides the opportunity to
      examine and test future scenarios for National Health Service (NHS) care.Aim The
      aim of this research was to explore the required skill-mix of the dental team to
      meet future need and demand of older people in England to 2028 utilising
      operational research methods and to examine a range of future scenarios.Method A
      three-stage computer model was developed to consider demand for dental care,
      workforce supply and skill-mix. First, the demand model combined population
      demography and a marker of oral health with attendance and treatment rates based
      on NHS activity data. Monte Carlo simulation was used to give an indication of
      the uncertainty surrounding this projected demand. Second, projections on
      workforce supply and other assumptions relating to clinical hours, NHS commitment
      and workforce whole time equivalents (WTEs) were analysed to produce a range of
      estimates for the current and future workforce. Third, staff skill-mix
      competencies were examined and the data fed into an optimisation model. Linear
      programming was used to give the optimal workforce makeup and predictions for
      workforce requirements. Five future scenarios were run from 'no skill-mix'
      through to 'maximum skill-mix' in the dental team, and the outputs
      compared.Results The results indicate that by 2028 there will be an increase in
      demand for care among older people of over 80% to almost 8.8 million hours;
      however, Monte Carlo simulation suggests considerable uncertainty surrounding the
      demand model outputs with demand deviating from the average in terms of treatment
      hours by as much as 22%. Modelling a healthcare system with 'no skill-mix'
      resulted in the lowest volume of clinical staff equivalents (dentists: 8,668)
      providing care for older people, whereas maximum skill-mix involved more staff
      (clinical staff = 10,337, of whom 2,623 were dentists, 4,180 hygienist/therapists
      and 3,534 clinical dental technicians) if all care is provided at the relevant
      level of competence.Conclusion The model suggests that with widening skill-mix,
      dental care professionals can play a major role in building dental care capacity
      for older people in future. The implications for health policy, professional
      bodies and dental teamworking are discussed.

PMID- 20147931
TI  - Evidence summary: why is access to dental care for frail elderly people worse
      than for other groups?
AB  - In August 2009, members of the newly redeveloped Primary Care Dentistry Research
      Forum (http://www.dentistryresearch.org) took part in an online vote to identify
      questions in day-to-day practice that they felt most needed to be answered with
      conclusive research. The question which received the most votes formed the
      subject of a critical appraisal of the relevant literature. Each month a new
      round of voting will take place to decide which further questions will be
      reviewed. Dental practitioners and dental care professionals are encouraged to
      take part in the voting and submit their own questions to be included in the vote
      by joining the website.This paper details a summary of the findings of the first
      critical appraisal. In conclusion, the critical appraisal has identified that
      primary research is needed to look at the subject of access to dental care for
      frail elderly people. Similar barriers to accessing care for this group of people
      are still being reported today as they were 20 years ago.

PMID- 20147932
TI  - Getting into medical school - a guide for dental graduates.
AB  - Dentists may apply to medical school with a view to ultimately specialising in
      oral and maxillofacial surgery or oral medicine. While there is much information
      on applying to medical school, very little is specific to the dental graduate.
      This paper discusses the contemporary admissions process including the
      application form, admissions tests, and interview.

PMID- 20147933
TI  - Evidence-informed dental student recruitment techniques.
AB  - The aim of the study described was to measure the performance of potential dental
      students in an evidence-based, objective, structured admission interview, and to
      compare that performance to student achievement in aptitude tests, tests of
      scientific knowledge, and tests of ability to apply knowledge to dentistry. A
      list of desirable attributes of dental professionals was drawn from the
      literature, omitting those which were considered to be learnt within the dental
      school curriculum. Possession of these attributes were then measured by
      objectively scoring responses to questions framed around a challenging clinical
      scenario. The interview scores were then correlated against student performance
      in an MCQ science for dentistry examination, an applied dental knowledge test,
      and the Graduate Australian Medical student aptitude test. The literature review
      revealed that sensitivity to others, professionalism, and ethical behaviour were
      deemed almost as important as academic and technical competency. Correlations of
      scores from an interview which sought to measure the attributes described in the
      literature with scores in scientific knowledge tests, aptitude tests and applied
      dental knowledge tests were low, and did not reach statistical significance. The
      results suggest that an interview process has been devised which measures the
      importance of characteristics not readily captured in more traditional selection
      strategies. Because the literature demonstrates that these characteristics are
      important to the public and the profession, this objective interview is a useful
      selection tool.

PMID- 20147958
TI  - Determinants of erectile dysfunction in type 2 diabetes.
AB  - This study was designed to evaluate the prevalence and correlates of ED in a
      population of diabetic men. Consecutive patients with type 2 diabetes were
      recruited among outpatients regularly attending Diabetes Clinics. Inclusion
      criteria for the initial selection of patients were a diagnosis of type 2
      diabetes for at least 6 months but less than 10 years, age 35-70 years, body mass
      index (BMI) of 24 or higher, HbA1c of 6.5% or higher: a total of 555 (90.8%) of
      the 611 men were analyzed in this study. ED was assessed by the IIEF-5
      instrument. Approximately, 6 in 10 men in our sample of diabetic men had varying
      degrees of erectile dysfunction: mild 9%, mild to moderate 11.2%, moderate 16.9%
      and severe 22.9%. The prevalence of severe ED increased with age. Higher
      hemoglobin A1c (HbA1c) levels were associated with ED; similarly, the presence of
      metabolic syndrome, hypertension, atherogenic dyslipidemia (low levels of HDL
      cholesterol and high levels of triglycerides) and depression was associated with
      ED. Physical activity was protective of ED; men with higher levels of physical
      activity were 10% less likely to have ED as compared with those with the lowest
      level. In conclusion, among subjects with type 2 diabetes glycemic control and
      other metabolic covariates were associated with ED risk, whereas higher level of
      physical activity was protective. These results encourage the implementation of
      current medical guidelines that place intensive lifestyle changes as the first
      step of the management of type 2 diabetes.

PMID- 20147959
TI  - Mortality in infants with congenital diaphragmatic hernia: a study of the United
      States National Database.
AB  - OBJECTIVE: To examine the effect of regionalization of care on outcomes of
      neonates with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We analyzed
      the National Inpatient Sample and the 'Kids' database for the years 1997 to 2004.
      Infants with CDH were grouped based on whether they underwent surgical repair at
      the hospital of birth, or at another facility. Groups were compared using chi
      square, t-test and logistic regression. RESULT: A total of 2140 infants were
      included: 41% were females, 42% were Caucasians, 48% were transported, 20%
      reported the use of extracorporeal membrane oxygenation (ECMO)and 33% died. Only
      79% underwent operative repair, in which 85% survived after surgery. Survival
      among operated patients who used ECMO was 40%. Transported infants used more ECMO
      than non-transported ones (25 vs 15%; adjusted odds ratio (OR) 1.46; confidence
      interval 1.1 to 1.9, P=0.007), and had higher mortality after surgery (16 vs 13%;
      adjusted OR 1.46; confidence interval 1.1 to 2, P=0.02). CONCLUSION: The
      utilization of neonatal transport of CDH patients is associated with increased
      mortality and increased need for ECMO. This study supports the need for
      regionalization of care, and favors maternal transport before delivery of CDH
      newborns.

PMID- 20147960
TI  - Predictors of survival in congenital diaphragmatic hernia patients requiring
      extracorporeal membrane oxygenation: CNMC 15-year experience.
AB  - OBJECTIVE: To review outcomes of patients with congenital diaphragmatic hernia
      (CDH) requiring extracorporeal membrane oxygenation (ECMO) at a level IIIC
      neonatal intensive care unit and to determine if pre-ECMO respiratory status can
      help predict mortality. STUDY DESIGN: A single-center retrospective chart review
      was conducted on all infants with CDH treated with ECMO in the past 15 years.
      Demographic and clinical information, including pre-ECMO ventilatory and blood
      gas data, was collected. Differences between survivors and non-survivors were
      evaluated using independent samples t-/Mann-Whitney U-and Fisher's exact/chi (2)
      tests for continuous and categorical data, respectively. Cox regression analysis
      was performed to evaluate predictors of survival while controlling for
      covariates. Significant predictors were further explored with receiver operating
      characteristic (ROC) curve and Kaplan-Meier survival analysis. RESULT: Overall
      survival of the population of 62 patients treated with ECMO was 50%. Survivor and
      non-survivors were similar in birth weight, gestational age, gender, race and
      Apgar scores. Approximately 80% of patients in both groups had a left-sided
      defect. Less than half of patients were prenatally diagnosed in either group.
      Patients in the non-survivor group had associated anomalies (42 vs 23% for
      survivors) but this was not statistically significant (P=0.303). Non-survivors
      were more likely to be put on ECMO earlier, stay on ECMO longer and be operated
      upon later. On pre-ECMO blood gas analyses, survivors had higher pH and PaO(2),
      and lower oxygenation index and PaCO(2) compared with non-survivors. After
      controlling for covariates, a lower minimum PaCO(2) and side of defect were the
      only independent predictors of survival. ROC curve for minimum pre-ECMO PaCO(2)
      had a significant area under the curve (0.72, P=0.003). Survival was 27% in
      babies unable to achieve a pre-ECMO PaCO(2) <60 mm Hg whereas no patients
      survived if their lowest pre-ECMO PaCO(2) was >70 mm Hg. CONCLUSION: Minimum
      achievable pre-ECMO PaCO(2) is an independent predictor of survival in patients
      with CDH requiring ECMO life support. These data provide useful prognostic
      information for counseling families and may facilitate direction of care in
      extreme cases where the degree of pulmonary hypoplasia may be incompatible with
      life.

PMID- 20147961
TI  - Antigen-specific CD4 cells assist CD8 T-effector cells in eliminating
      keratinocytes.
AB  - Keratinocytes expressing tumor or viral antigens can be eliminated by antigen
      primed CD8 cytotoxic T cells. CD4 T-helper cells help induction of CD8 cytotoxic
      T cells from naive precursors and generation of CD8 T-cell memory. In this study,
      we show, unexpectedly, that CD4 cells are also required to assist primed CD8
      effector T cells in rejection of skin expressing human growth hormone, a neo-self
      antigen, in keratinocytes. The requirement for CD4 cells can be substituted by
      CD40 costimulation. Rejection of skin expressing ovalbumin (OVA), a non-self
      antigen, by primed CD8 cytotoxic T cells can in contrast occur without help from
      antigen-specific CD4 T cells. However, rejection of OVA expressing keratinocytes
      is helped by antigen-specific CD4 T cells if only low numbers of primed or naive
      OVA-specific CD8 T cells are available. Effective immunotherapy directed at
      antigens expressed in squamous cancer may therefore be facilitated by induction
      of tumor antigen-specific CD4 helper T cells, as well as cytotoxic CD8 T cells.

PMID- 20147962
TI  - Enhanced global genome nucleotide excision repair reduces UV carcinogenesis and
      nullifies strand bias in p53 mutations in Csb-/- mice.

PMID- 20147963
TI  - Autoantibodies in scurfy mice and IPEX patients recognize keratin 14.
AB  - Scurfy mice have a deletion in the Foxp3 gene, resulting in a failure to generate
      Foxp3(+) regulatory T cells, and they subsequently develop severe CD4(+) T-cell
      mediated autoimmune inflammation. Multiple organs are involved, but the skin is
      one of the main organs affected. During the course of disease, Scurfy mice
      develop autoantibodies; however, the targeted antigens are unknown. In this
      study, we show that Scurfy mice develop autoantibodies directed against skin
      antigens. Using western blot analysis, we found that Scurfy serum reacted with
      proteins in total skin lysate, as well as in a keratinocyte lysate. Most of the
      Scurfy sera tested identified a major band at 50 kDa. Transfer of Scurfy CD4(+) T
      cells into nu/nu mice yielded autoantibodies with similar reactivity. Further
      analysis using 2D western blots, followed by peptide mass fingerprinting,
      identified several keratins as targets. To confirm this observation, we chose one
      of the identified targets, keratin 14, and prepared recombinant proteins
      encompassing the N-terminal, middle, and C-terminal portions of the keratin 14
      protein. Scurfy serum predominantly recognized the C-terminal fragment. Sera from
      patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked
      (IPEX) syndrome, the human disease resulting from FOXP3 mutations, also
      recognized skin antigens, including keratin 14. Thus, the results of our study
      indicate that autoantibodies in Scurfy mice and patients with IPEX target
      keratins.

PMID- 20147964
TI  - Intravital imaging of IL-1beta production in skin.
AB  - IL-1 is a prototypic inflammatory cytokine that has pathogenic roles in various
      skin disorders. Although Langerhans cells (LCs) have been reported to express IL
      1beta mRNA upon application of contact sensitizers, it remains unclear whether
      other cell types produce IL-1beta in skin. Thus, we sought to directly identify
      IL-1beta-producing cells in living animals by construction of transgenic mice
      expressing DsRed fluorescence protein gene under the control of IL-1beta
      promoter. Little DsRed fluorescence signal was detected in skin under steady
      state conditions. Striking increases in DsRed signal were observed after topical
      application of a contact sensitizer, oxazolone, which also induced markedly
      elevated IL-1beta mRNA and protein expression. DsRed signal was expressed
      primarily by CD45(+)/CD11b(+) myeloid leukocytes in both epidermal and dermal
      compartments and was detected only in small fractions of epidermal LCs.
      Interestingly, DsRed(+) cells emerged preferentially as clusters around hair
      follicles. Intravital confocal imaging experiments revealed highly motile
      potentials of DsRed(+) cells-they constantly crawled around hair follicles via
      amoeba-like movements with a mean velocity of 1.0+/-0.4 microm min(-1)
      (epidermis) or 2.7+/-1.4 microm min(-1) (dermis). The newly developed in vivo
      imaging system represents a useful tool for studying spatial regulation of IL
      1beta production in skin.

PMID- 20147965
TI  - Slug (Snai2) expression during skin and hair follicle development.

PMID- 20147966
TI  - Regulation of human skin pigmentation in situ by repetitive UV exposure:
      molecular characterization of responses to UVA and/or UVB.
AB  - UV radiation is a major environmental factor that affects pigmentation in human
      skin and can eventually result in various types of UV-induced skin cancers. The
      effects of various wavelengths of UV on melanocytes and other types of skin cells
      in culture have been studied, but little is known about gene expression patterns
      in situ following in situ exposure of human skin to different types of UV (UVA
      and/or UVB). Paracrine factors expressed by keratinocytes and/or fibroblasts that
      affect skin pigmentation might be regulated differently by UV, as might their
      corresponding receptors expressed on melanocytes. To test the hypothesis that
      different mechanisms are involved in the pigmentary responses of the skin to
      different types of UV, we used immunohistochemical and whole human genome
      microarray analyses to characterize human skin in situ to examine how melanocyte
      specific proteins and paracrine melanogenic factors are regulated by repetitive
      exposure to different types of UV compared with unexposed skin as a control. The
      results show that gene expression patterns induced by UVA or UVB are distinct-UVB
      eliciting dramatic increases in a large number of genes involved in pigmentation
      as well as in other cellular functions, whereas UVA had little or no effect on
      these. The expression patterns characterize the distinct responses of the skin to
      UVA or UVB, and identify several potential previously unidentified factors
      involved in UV-induced responses of human skin.

PMID- 20147968
TI  - The antihypertensive effect of fermented milk in individuals with prehypertension
      or borderline hypertension.
AB  - Fermented milk (FM) with putative antihypertensive effect in humans could be an
      easy applicable lifestyle intervention against hypertension. The mode of action
      is supposed to be through active milk peptides, shown to possess in vitro ACE
      inhibitory effect. Blood pressure (BP) reductions upto 23 mm Hg have been
      reported in spontaneously hypertensive rats fed FM. Results from human studies of
      the antihypertensive effect are inconsistent. However, many studies suffer from
      methodological weaknesses, as insufficient blinding and the use of office BP
      measurements. We conducted a randomised, double-blind placebo-controlled study of
      the antihypertensive effect of Lactobacillus helveticus FM in 94 prehypertensive
      and borderline hypertensive subjects. The participants were randomised into three
      treatment groups with a daily intake of 150 ml of FM, 300 ml of FM or placebo
      (chemically acidified milk). The primary outcome was repeated 24-h ambulatory BP
      measurements. There were no statistically significant differences in the outcome
      between the groups (systolic BP (SBP), P=0.9; diastolic BP (DBP), P=0.2).
      However, the group receiving 300 ml FM had reduced BP across the 8-week period in
      several readings, which could be compatible with a minor antihypertensive effect.
      Heart rate and lipids remained unchanged between groups. Hence, our study does
      not support earlier studies measuring office BP-measurements, reporting
      antihypertensive effect of FM. Based on straight performed 24-h ambulatory BP
      measurements, milk fermented with Lactobacillus helveticus does not posses
      significant antihypertensive effect.

PMID- 20147967
TI  - Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal
      tumours - implications for personalised cancer medicine.
AB  - BACKGROUND: Response to EGFR-targeted therapies in colorectal cancer patients has
      been convincingly associated with Kirsten-Ras (K-Ras) mutation status. Current
      mandatory mutation testing for patient selection is limited to the K-Ras
      'hotspot' codons 12 and 13. METHODS: Colorectal tumours (n=106) were screened for
      additional K-Ras mutations, phenotypes compared in transformation and Ras GTPase
      activating assays and gene and pathway changes induced by individual K-Ras
      mutants identified by microarray analysis. Taqman-based gene copy number and FISH
      analyses were used to investigate K-Ras gene amplification. RESULTS: Four
      additional K-Ras mutations (Leu(19)Phe (1 out of 106 tumours), Lys(117)Asn (1 out
      of 106), Ala(146)Thr (7 out of 106) and Arg(164)Gln (1 out of 106)) were
      identified. Lys(117)Asn and Ala(146)Thr had phenotypes similar to the hotspot
      mutations, whereas Leu(19)Phe had an attenuated phenotype and the Arg(164)Gln
      mutation was phenotypically equivalent to wt K-Ras. We additionally identified a
      new K-Ras gene amplification event, present in approximately 2% of tumours.
      CONCLUSIONS: The identification of mutations outwith previously described hotspot
      codons increases the K-Ras mutation burden in colorectal tumours by one-third.
      Future mutation screening to facilitate optimal patient selection for treatment
      with EGFR-targeted therapies should therefore be extended to codon 146, and in
      addition should consider the unique molecular signatures associated with
      individual K-Ras mutations.

PMID- 20147969
TI  - Non-synonymous single-nucleotide polymorphisms associated with blood pressure and
      hypertension.
AB  - In this study, we determined the association of 1180 non-synonymous single
      nucleotide polymorphisms (SNPs) with systolic blood pressure (SBP) and
      hypertensive status. A total of 8842 subjects were taken from two community-based
      cohorts--Ansung (n=4183) and Ansan (n=4659), South Korea--which had been
      established for genome-wide association studies (GWAS). Five SNPs (rs16835244,
      rs2286672, rs6265, rs17237198 and rs7312017) were significantly associated (P
      values: 0.003-0.0001, not corrected for genome-wide significance) with SBP in
      both cohorts. Of these SNPs, rs16835244 and rs2286672 correlated with risk for
      hypertension. The rs16835244 SNP replaces Ala288 in arginine decarboxylase (ADC)
      with serine, and rs2286672 replaces Arg172 in phospholipase D2 (PLD2) with
      cysteine. A comparison of peptide sequences between vertebrate homologues
      revealed that the SNPs identified occur at conserved amino-acid residues. In
      silico analysis of the protein structure showed that the substitution of a polar
      residue, serine, for a non-polar alanine at amino-acid residue 288 affects a
      conformational change in ADC, and that Arg172 in PLD2 resides in the PX domain,
      which is important for membrane trafficking. These results provide insights into
      the function of these non-synonymous SNPs in the development of hypertension. The
      study investigating non-synonymous SNPs from GWAS not only by statistical
      association analysis but also by biological relevance through the protein
      structure might be a good approach for identifying genetic risk factors for
      hypertension, in addition to discovering causative variations.

PMID- 20147970
TI  - Uric acid and the cardiovascular profile of African and Caucasian men.
AB  - The African population is considered a high-risk group for the development of
      hypertension, and identifying risk factors are therefore essential in preventive
      actions against cardiovascular disease (CVD). Elevated levels of uric acid (UA)
      are often associated with CVD. Our first aim was to establish possible ethnic
      differences in UA levels between African and Caucasian men. Our second aim was to
      determine any associations between UA levels and cardio-metabolic variables, and
      also how these correlates differ between the two groups. African (N=87) and
      Caucasian (N=121) men participated in this cross-sectional study. Our results
      have shown that African men had significantly lower (353+/-87.7 vs 401+/-98.2;
      P<0.01) UA levels compared with Caucasian men. Waist circumference and
      triglycerides correlated strongly with UA in both ethnic groups. This was
      confirmed with a forward stepwise multiple regression analysis. After adjustment
      for confounders, the correlation between UA and triglycerides remained
      significant only in the Caucasians (r=0.29; P=0.02), whereas only the African men
      showed an independent correlation between UA and total peripheral resistance
      (TPR) (r=0.23; P=0.04). TPR increased significantly across UA tertiles only in
      the African men (P=0.01 vs P=0.96). In conclusion, despite their lower UA levels,
      Africans showed an independent relationship between UA and vascular resistance,
      indicating a possible explanation for their high prevalence of hypertension.

PMID- 20147971
TI  - A 52-week prospective, cohort study of the effects of losartan with or without
      hydrochlorothiazide (HCTZ) in hypertensive patients with metabolic syndrome.
AB  - The impact of an ARB, with or without hydrochlorothiazide (HCTZ), on glycaemic
      factors and the risk for developing diabetes in hypertensive patients with the
      metabolic syndrome have not been fully assessed. This was a 52-week multicentre,
      prospective, phase-IV, open-label, cohort study of losartan or losartan/HCTZ in
      hypertensive patients with metabolic syndrome. All subjects were treated
      initially with losartan 50 mg day(-1). Those not achieving target blood pressure
      (BP <140/90 mm Hg) were titrated sequentially to losartan 100 mg, losartan 100
      mg/HCTZ 12.5 mg, losartan 100 mg/HCTZ 25 mg and finally to losartan 100 mg/HCTZ
      25 mg and calcium-channel blocker (CCB), as required. The primary glycaemic
      outcome measure was change in fasting blood glucose (FBG) and glycosylated
      haemoglobin A1c (HbA1c) at 52 weeks of treatment. Among the 1897 potentially
      eligible patients enrolled in the study, 1714 fulfilled the screening criteria.
      During the 52-week treatment period of the study, FBG and HbA1c did not change
      significantly. Clinically important and statistically significant changes were
      observed for both the systolic (SBP) and diastolic BP (DBP) during the study
      treatment period, with an overall mean decrease of 16.95 mm Hg in SBP (P=0.001)
      and 9.84 mm Hg in DBP (P=0.001). The majority of the patients (77.3%) achieved a
      target BP of <140/90 mm Hg. In conclusion, losartan, either alone or in
      combination with HCTZ, is effective in managing hypertension without inducing any
      change in glycaemic parameters or increasing the risk for developing diabetes in
      hypertensive patients with the metabolic syndrome.

PMID- 20147972
TI  - Body mass index trend and its association with blood pressure distribution in
      children.
AB  - The aim of the study was to examine the association of a trend in body mass index
      (BMI) status with current blood pressure in a cohort of school children from
      South India. A population of 25,228 children was selected using stratified random
      sampling method. Height and weight were measured in 2003-2004. Height, weight and
      blood pressure were measured in 2005-2006. A total of 12,129 children aged 5-16
      years having paired data were analysed. Blood pressure and BMI values were
      converted to Z scores using International paediatric reference values. An
      increase in Z BMI meant that the child is moving to a higher BMI level with
      respect to his or her age and sex. In the cohort, 62.4% children had a higher Z
      BMI at follow-up than at baseline. Children with higher Z BMI at follow-up were
      labelled as positive BMI status group (PBSG) and the remaining as negative BMI
      status group (NBSG). The positive trend in BMI was more in rural areas,
      government schools and girls. In all subgroups, PBSG showed significantly higher
      systolic blood pressures (SBPs) than NBSG. PBSG showed significantly higher
      diastolic blood pressures (DBPs) in urban area, government schools and girls when
      compared with NBSG. Prevalence of first instance systolic hypertension was more
      in PBSG in all the subgroups except in rural children. Prevalence of diastolic
      hypertension was significantly higher in PBSG in urban subgroup only. BMI status
      trends are associated with blood pressure distribution in children.

PMID- 20147973
TI  - Lck is a key target of imatinib and dasatinib in T-cell activation.

PMID- 20147974
TI  - Chronic myeloid leukemia CD34+ cells have reduced uptake of imatinib due to low
      OCT-1 activity.
AB  - Active influx of imatinib in chronic myeloid leukemia (CML) cells is mediated by
      the organic cation transporter 1 (OCT-1). Functional activity of OCT-1 (OCT-1
      Activity) in mononuclear cells is an excellent predictor of molecular response
      over the first 24 months of imatinib therapy for chronic phase patients. CML
      progenitor cells are less sensitive to imatinib-induced apoptosis and are likely
      contributors to disease persistence. We investigated whether alterations in the
      expression and function of OCT-1 have a role in imatinib resistance in
      progenitors. We found the intracellular uptake and retention (IUR) of imatinib,
      OCT-1 Activity and OCT-1 mRNA expression are all significantly lower in CML CD34+
      cells compared with mature CD34- cells (P<0.001). However, no differences in IUR
      or OCT-1 Activity were observed between these subsets in healthy donors. In
      contrast to OCT-1, ABCB1 and ABCG2 seemed to have no functional role in the
      transport of imatinib in CML CD34+ cells. Consistent with the observation that
      nilotinib uptake is not OCT-1 dependent, the IUR of nilotinib did not differ
      between CML CD34+ and CD34- cells. These results indicate that low imatinib
      accumulation in primitive CML cells, mediated through reduced OCT-1 Activity may
      be a critical determinant of long-term disease persistence.

PMID- 20147975
TI  - Specific induction of CD33 expression by E2A-HLF: the first evidence for aberrant
      myeloid antigen expression in ALL by a fusion transcription factor.

PMID- 20147976
TI  - Aurora kinase inhibitors: novel small molecules with promising activity in acute
      myeloid and Philadelphia-positive leukemias.
AB  - Aurora kinases are a family of protein kinases that have a key role in multiple
      stages of mitosis. Over-expression of Aurora kinases, particularly Aurora A, has
      been demonstrated in a number of solid tumors and hematological malignancies. Not
      surprisingly, these serine/threonine kinases have become attractive small
      molecule targets for cancer therapeutics, with several inhibitors currently in
      early-phase clinical trials. A small number of compounds developed to date are
      highly selective for either Aurora A or Aurora B, while the majority inhibit both
      Aurora A and Aurora B; many of these compounds exhibit 'off-target' inhibition of
      kinases such as ABL, JAK2 and FLT3. It is currently unclear whether the
      therapeutic activity of these compounds in leukemia is primarily due to selective
      Aurora or multi-kinase inhibition. The most promising application for Aurora
      kinase inhibitors to date appears to be in FLT3-mutated acute myeloid leukemia
      (AML) and imatinib-resistant chronic myeloid leukemia/Philadelphia chromosome
      positive (Ph+) acute lymphoblastic leukemia, particularly when caused by the
      T315I mutation. Here we review the growing body of evidence supporting the use of
      Aurora kinase inhibitors as effective agents for AML and Ph+ leukemias.

PMID- 20147977
TI  - SHIP-1 inhibits CD95/APO-1/Fas-induced apoptosis in primary T lymphocytes and T
      leukemic cells by promoting CD95 glycosylation independently of its phosphatase
      activity.
AB  - SHIP-1 (SH2 (Src homology 2)-containing inositol 5'-phosphatase-1) functions as a
      negative regulator of immune responses by hydrolyzing phosphatidylinositol-3,4,5
      triphosphate generated by phosphoinositide-3 (PI 3)-kinase activity. As a result,
      SHIP-1 deficiency in mice results in myeloproliferation and B-cell lymphoma. On
      the other hand, SHIP-1-deficient mice have a reduced T-cell population, but the
      underlying mechanisms are unknown. In this work, we hypothesized that SHIP-1
      plays anti-apoptotic functions in T cells upon stimulation of the death receptor
      CD95/APO-1/Fas. Using primary T cells from SHIP-1(-/-) mice and T leukemic cell
      lines, we report that SHIP-1 is a potent inhibitor of CD95-induced death. We
      observed that a small fraction of the SHIP-1 pool is localized to the endoplasmic
      reticulum (ER), in which it promotes CD95 glycosylation. This post-translational
      modification requires an intact SH2 domain of SHIP-1, but is independent of its
      phosphatase activity. The glycosylated CD95 fails to oligomerize upon
      stimulation, resulting in impaired death-inducing signaling complex (DISC)
      formation and downstream apoptotic cascade. These results uncover an
      unanticipated inhibitory function for SHIP-1 and emphasize the role of
      glycosylation in the regulation of CD95 signaling in T cells. This work may also
      provide a new basis for therapeutic strategies using compounds inducing apoptosis
      through the CD95 pathway on SHIP-1-negative leukemic T cells.

PMID- 20147978
TI  - Allogeneic hematopoietic stem-cell transplantation in AML and MDS using
      myeloablative versus reduced-intensity conditioning: long-term follow-up.

PMID- 20147980
TI  - Nilotinib does not significantly reduce imatinib OCT-1 activity in either cell
      lines or primary CML cells.

PMID- 20147979
TI  - Monitoring of adenovirus load in stool by real-time PCR permits early detection
      of impending invasive infection in patients after allogeneic stem cell
      transplantation.
AB  - Invasive adenovirus (AdV) infections are associated with high morbidity and
      mortality in allogeneic stem cell transplant recipients. We observed that
      molecular detection of the virus in stool specimens commonly precedes AdV
      viremia, suggesting that intestinal infections may represent a common source of
      virus dissemination. To address this notion, we have investigated 153 consecutive
      allogeneic transplantations in 138 pediatric patients by quantitative monitoring
      of AdV in stool specimens and peripheral blood by a pan-adenovirus real-time (RQ)
      PCR approach. AdV was detectable in serial stool specimens in all cases of AdV
      viremia during the post-transplant course (P<0.0001). The incidence of AdV
      viremia in individuals with peak virus levels in stool specimens above 1 x 10E6
      copies per gram (n=22) was 73% vs 0% in patients with AdV levels in stool
      specimens below this threshold (n=29; P<0.0001). Serial measurement of AdV levels
      in stool specimens by RQ-PCR permitted early diagnosis of impending invasive
      infection with a sensitivity and specificity of 100% (95% confidence interval
      (CI) 96-100%) and 83% (95% CI 67-92%), respectively. The median time span between
      detection of AdV loads in stool specimens above 1 x 10E6 copies per gram and
      first observation of viremia was 11 days (range 0-192). Quantitative monitoring
      of the AdV load in stool specimens therefore provides a rationale for early
      initiation of antiviral treatment with the aim of preventing progression to life
      threatening invasive infection.

PMID- 20147981
TI  - Human leukocyte antigen (HLA) A1-B8-DR3 (8.1) haplotype, tumor necrosis factor
      (TNF) G-308A, and risk of non-Hodgkin lymphoma.

PMID- 20147982
TI  - Progress and prospects: Immunobiology of gene therapy for neurodegenerative
      disease: prospects and risks.
AB  - Gene therapy for neurological, and in particular neurodegenerative, disease is
      now a reality. A number of early phase clinical trials have been completed and
      several are currently in progress. In view of this, it is critically important to
      evaluate the immunological risk associated with neurological gene therapy, which
      has clear implications for trial safety and efficacy. Moreover, it is imperative
      in particular to identify factors indicating potential high risk. In the light of
      recent advances in understanding immune regulation in the central nervous system
      (CNS) and with the continued development of new gene delivery vectors, this
      review critically assesses the current knowledge of immunobiology within the CNS
      in terms of likely immunological risk pertaining to viral vectors and gene
      therapy applications for neurodegenerative disease.

PMID- 20147983
TI  - Characterisation of microbial communities colonising the hyphal surfaces of
      arbuscular mycorrhizal fungi.
AB  - Arbuscular mycorrhizal fungi (AMF) are symbiotic soil fungi that are intimately
      associated with the roots of the majority of land plants. They colonise the
      interior of the roots and the hyphae extend into the soil. It is well known that
      bacterial colonisation of the rhizosphere can be crucial for many pathogenic as
      well as symbiotic plant-microbe interactions. However, although bacteria
      colonising the extraradical AMF hyphae (the hyphosphere) might be equally
      important for AMF symbiosis, little is known regarding which bacterial species
      would colonise AMF hyphae. In this study, we investigated which bacterial
      communities might be associated with AMF hyphae. As bacterial-hyphal attachment
      is extremely difficult to study in situ, we designed a system to grow AMF hyphae
      of Glomus intraradices and Glomus proliferum and studied which bacteria separated
      from an agricultural soil specifically attach to the hyphae. Characterisation of
      attached and non-attached bacterial communities was performed using terminal
      restriction fragment length polymorphism and clone library sequencing of 16S
      ribosomal RNA (rRNA) gene fragments. For all experiments, the composition of
      hyphal attached bacterial communities was different from the non-attached
      communities, and was also different from bacterial communities that had attached
      to glass wool (a non-living substratum). Analysis of amplified 16S rRNA genes
      indicated that in particular bacteria from the family of Oxalobacteraceae were
      highly abundant on AMF hyphae, suggesting that they may have developed specific
      interactions with the fungi.

PMID- 20147984
TI  - Distributions of putative aerobic methanotrophs in diverse pelagic marine
      environments.
AB  - Aerobic methane oxidization in the pelagic ocean serves an important role in
      limiting methane release to the atmosphere, yet little is known about the
      identity and distribution of bacteria that mediate this process. The distribution
      of putative methane-oxidizing marine groups, OPU1, OPU3 and Group X, was assessed
      in different ocean provinces using a newly developed fingerprinting method
      (monooxygenase intergenic spacer analysis (MISA)) in combination with pmoA clone
      library analysis and quantitative PCR (qPCR). The distribution of these three
      distinct monooxygenase groups, previously reported from pelagic marine
      environments, was examined in 39 samples including active methane seeps in the
      Gulf of Mexico and Santa Monica Bay, submarine canyon heads along the California
      continental margin, an oligotrophic subtropical gyre and areas proximal to a
      hydrothermal vent in the North Fiji back-arc basin. OPU1 and OPU3 were widely and
      similarly distributed within the meso- and bathypelagic zone (110 to
      approximately 2000 m water depth) and showed a >50-fold greater abundance near
      methane seeps relative to non-seep sites. In contrast, Group X was predominantly
      recovered from samples along the California margin, at both seep and non-seep
      sites. All three phylotypes were below detection in the epipelagic zone to depths
      of 100 m. Several additional deeply branching monooxygenase sequences were also
      identified in this study, indicating the presence of uncharacterized groups of
      microorganisms potentially involved in the cycling of methane or ammonium.

PMID- 20147985
TI  - Viral and microbial community dynamics in four aquatic environments.
AB  - The species composition and metabolic potential of microbial and viral
      communities are predictable and stable for most ecosystems. This apparent
      stability contradicts theoretical models as well as the viral-microbial dynamics
      observed in simple ecosystems, both of which show Kill-the-Winner behavior
      causing cycling of the dominant taxa. Microbial and viral metagenomes were
      obtained from four human-controlled aquatic environments at various time points
      separated by one day to >1 year. These environments were maintained within narrow
      geochemical bounds and had characteristic species composition and metabolic
      potentials at all time points. However, underlying this stability were rapid
      changes at the fine-grained level of viral genotypes and microbial strains. These
      results suggest a model wherein functionally redundant microbial and viral taxa
      are cycling at the level of viral genotypes and virus-sensitive microbial
      strains. Microbial taxa, viral taxa, and metabolic function persist over time in
      stable ecosystems and both communities fluctuate in a Kill-the-Winner manner at
      the level of viral genotypes and microbial strains.

PMID- 20147989
TI  - South Africa's opportunity.

PMID- 20147990
TI  - Divide and conquer.

PMID- 20147986
TI  - Chronic DLL4 blockade induces vascular neoplasms.
AB  - Delta-like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target
      for cancer therapy. However, the potential side effects of blocking this pathway
      remain uncertain. Here we show that chronic DLL4 blockade causes pathological
      activation of endothelial cells, disrupts normal organ homeostasis and induces
      vascular tumours, raising important safety concerns.

PMID- 20147991
TI  - A framework for success.

PMID- 20147997
TI  - Journal club. A computational geneticist looks at mechanisms of chromosomal
      evolution.

PMID- 20148003
TI  - Science lines up for seat to space.

PMID- 20148004
TI  - Still looking for that woodpecker.

PMID- 20148005
TI  - Testing time for stem cells.

PMID- 20148006
TI  - Delays prompt reshuffle at ITER fusion project.

PMID- 20148007
TI  - The future of European research.

PMID- 20148009
TI  - South African science: black, white and grey.

PMID- 20148008
TI  - Palaeogenetics: Icy resolve.

PMID- 20148010
TI  - Did the bunny sell or sully the story on toxicity testing?

PMID- 20148011
TI  - Iranian physics society striving to prevent misconduct.

PMID- 20148012
TI  - Italy's stem-cell challenge gaining momentum.

PMID- 20148013
TI  - Still a way to go for South Africa's science revolution.

PMID- 20148014
TI  - IPCC: cherish it, tweak it or scrap it?

PMID- 20148015
TI  - AIDS research must link to local policy.

PMID- 20148019
TI  - Q&A: Carl Zimmer on writing popular-science books. Interview by Nicola Jones.

PMID- 20148020
TI  - Evolutionary biology: Face of the past reconstructed.

PMID- 20148021
TI  - Nuclear physics: Weighing up the superheavies.

PMID- 20148024
TI  - Cosmology: Census at a distance.

PMID- 20148023
TI  - Palaeontology: Decay distorts ancestry.

PMID- 20148025
TI  - Neuroscience: Lack of inhibition leads to abuse.

PMID- 20148026
TI  - Parkinson's disease: Mitochondrial damage control.

PMID- 20148027
TI  - Astrophysics: Less greedy galaxies gulp gas.

PMID- 20148028
TI  - The next generation of scenarios for climate change research and assessment.
AB  - Advances in the science and observation of climate change are providing a clearer
      understanding of the inherent variability of Earth's climate system and its
      likely response to human and natural influences. The implications of climate
      change for the environment and society will depend not only on the response of
      the Earth system to changes in radiative forcings, but also on how humankind
      responds through changes in technology, economies, lifestyle and policy.
      Extensive uncertainties exist in future forcings of and responses to climate
      change, necessitating the use of scenarios of the future to explore the potential
      consequences of different response options. To date, such scenarios have not
      adequately examined crucial possibilities, such as climate change mitigation and
      adaptation, and have relied on research processes that slowed the exchange of
      information among physical, biological and social scientists. Here we describe a
      new process for creating plausible scenarios to investigate some of the most
      challenging and important questions about climate change confronting the global
      community.

PMID- 20148029
TI  - Ancient human genome sequence of an extinct Palaeo-Eskimo.
AB  - We report here the genome sequence of an ancient human. Obtained from
      approximately 4,000-year-old permafrost-preserved hair, the genome represents a
      male individual from the first known culture to settle in Greenland. Sequenced to
      an average depth of 20x, we recover 79% of the diploid genome, an amount close to
      the practical limit of current sequencing technologies. We identify 353,151 high
      confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been
      reported previously. We estimate raw read contamination to be no higher than
      0.8%. We use functional SNP assessment to assign possible phenotypic
      characteristics of the individual that belonged to a culture whose location has
      yielded only trace human remains. We compare the high-confidence SNPs to those of
      contemporary populations to find the populations most closely related to the
      individual. This provides evidence for a migration from Siberia into the New
      World some 5,500 years ago, independent of that giving rise to the modern Native
      Americans and Inuit.

PMID- 20148031
TI  - Neural bases for addictive properties of benzodiazepines.
AB  - Benzodiazepines are widely used in clinics and for recreational purposes, but
      will lead to addiction in vulnerable individuals. Addictive drugs increase the
      levels of dopamine and also trigger long-lasting synaptic adaptations in the
      mesolimbic reward system that ultimately may induce the pathological behaviour.
      The neural basis for the addictive nature of benzodiazepines, however, remains
      elusive. Here we show that benzodiazepines increase firing of dopamine neurons of
      the ventral tegmental area through the positive modulation of GABA(A) (gamma
      aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition,
      which relies on alpha1-containing GABA(A) receptors expressed in these cells,
      triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine
      neurons and underlies drug reinforcement. Taken together, our data provide
      evidence that benzodiazepines share defining pharmacological features of
      addictive drugs through cell-type-specific expression of alpha1-containing
      GABA(A) receptors in the ventral tegmental area. The data also indicate that
      subunit-selective benzodiazepines sparing alpha1 may be devoid of addiction
      liability.

PMID- 20148033
TI  - High molecular gas fractions in normal massive star-forming galaxies in the young
      Universe.
AB  - Stars form from cold molecular interstellar gas. As this is relatively rare in
      the local Universe, galaxies like the Milky Way form only a few new stars per
      year. Typical massive galaxies in the distant Universe formed stars an order of
      magnitude more rapidly. Unless star formation was significantly more efficient,
      this difference suggests that young galaxies were much more molecular-gas rich.
      Molecular gas observations in the distant Universe have so far largely been
      restricted to very luminous, rare objects, including mergers and quasars, and
      accordingly we do not yet have a clear idea about the gas content of more normal
      (albeit massive) galaxies. Here we report the results of a survey of molecular
      gas in samples of typical massive-star-forming galaxies at mean redshifts <z> of
      about 1.2 and 2.3, when the Universe was respectively 40% and 24% of its current
      age. Our measurements reveal that distant star forming galaxies were indeed gas
      rich, and that the star formation efficiency is not strongly dependent on cosmic
      epoch. The average fraction of cold gas relative to total galaxy baryonic mass at
      z = 2.3 and z = 1.2 is respectively about 44% and 34%, three to ten times higher
      than in today's massive spiral galaxies. The slow decrease between z
      approximately 2 and z approximately 1 probably requires a mechanism of semi
      continuous replenishment of fresh gas to the young galaxies.

PMID- 20148032
TI  - Rfx6 directs islet formation and insulin production in mice and humans.
AB  - Insulin from the beta-cells of the pancreatic islets of Langerhans controls
      energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus.
      During embryonic development, the transcription factor neurogenin 3 (Neurog3)
      initiates the differentiation of the beta-cells and other islet cell types from
      pancreatic endoderm, but the genetic program that subsequently completes this
      differentiation remains incompletely understood. Here we show that the
      transcription factor Rfx6 directs islet cell differentiation downstream of
      Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types
      except for pancreatic-polypeptide-producing cells. In human infants with a
      similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and
      subsequent sequencing identified mutations in the human RFX6 gene. These studies
      demonstrate a unique position for Rfx6 in the hierarchy of factors that
      coordinate pancreatic islet development in both mice and humans. Rfx6 could prove
      useful in efforts to generate beta-cells for patients with diabetes.

PMID- 20148034
TI  - Direct mass measurements above uranium bridge the gap to the island of stability.
AB  - The mass of an atom incorporates all its constituents and their interactions. The
      difference between the mass of an atom and the sum of its building blocks (the
      binding energy) is a manifestation of Einstein's famous relation E = mc(2). The
      binding energy determines the energy available for nuclear reactions and decays
      (and thus the creation of elements by stellar nucleosynthesis), and holds the key
      to the fundamental question of how heavy the elements can be. Superheavy elements
      have been observed in challenging production experiments, but our present
      knowledge of the binding energy of these nuclides is based only on the detection
      of their decay products. The reconstruction from extended decay chains introduces
      uncertainties that render the interpretation difficult. Here we report direct
      mass measurements of trans-uranium nuclides. Located at the farthest tip of the
      actinide species on the proton number-neutron number diagram, these nuclides
      represent the gateway to the predicted island of stability. In particular, we
      have determined the mass values of (252-254)No (atomic number 102) with the
      Penning trap mass spectrometer SHIPTRAP. The uncertainties are of the order of 10
      keV/c(2) (representing a relative precision of 0.05 p.p.m.), despite minute
      production rates of less than one atom per second. Our experiments advance direct
      mass measurements by ten atomic numbers with no loss in accuracy, and provide
      reliable anchor points en route to the island of stability.

PMID- 20148035
TI  - Above-room-temperature ferroelectricity in a single-component molecular crystal.
AB  - Ferroelectrics are electro-active materials that can store and switch their
      polarity (ferroelectricity), sense temperature changes (pyroelectricity),
      interchange electric and mechanical functions (piezoelectricity), and manipulate
      light (through optical nonlinearities and the electro-optic effect): all of these
      functions have practical applications. Topological switching of pi-conjugation in
      organic molecules, such as the keto-enol transformation, has long been
      anticipated as a means of realizing these phenomena in molecular assemblies and
      crystals. Croconic acid, an ingredient of black dyes, was recently found to have
      a hydrogen-bonded polar structure in a crystalline state. Here we demonstrate
      that application of an electric field can coherently align the molecular
      polarities in crystalline croconic acid, as indicated by an increase of optical
      second harmonic generation, and produce a well-defined polarization hysteresis at
      room temperature. To make this simple pentagonal molecule ferroelectric, we
      switched the pi-bond topology using synchronized proton transfer instead of rigid
      body rotation. Of the organic ferroelectrics, this molecular crystal exhibits the
      highest spontaneous polarization ( approximately 20 muC cm(-2)) in spite of its
      small molecular size, which is in accord with first-principles electronic
      structure calculations. Such high polarization, which persists up to 400 K, may
      find application in active capacitor and nonlinear optics elements in future
      organic electronics.

PMID- 20148036
TI  - Zonal flow formation in the Earth's core.
AB  - Zonal jets are very common in nature. Well-known examples are those in the
      atmospheres of giant planets and the alternating jet streams found in the Earth's
      world ocean. Zonal flow formation in nuclear fusion devices is also well studied.
      A common feature of these zonal flows is that they are spontaneously generated in
      turbulent systems. Because the Earth's outer core is believed to be in a
      turbulent state, it is possible that there is zonal flow in the liquid iron of
      the outer core. Here we report an investigation at the current low-viscosity
      limit of numerical simulations of the geodynamo. We find a previously unknown
      convection regime of the outer core that has a dual structure comprising inner,
      sheet-like radial plumes and an outer, westward cylindrical zonal flow. We
      numerically confirm that the dual-convection structure with such a zonal flow is
      stable under a strong, self-generated dipole magnetic field.

PMID- 20148037
TI  - Mical links semaphorins to F-actin disassembly.
AB  - How instructive cues present on the cell surface have their precise effects on
      the actin cytoskeleton is poorly understood. Semaphorins are one of the largest
      families of these instructive cues and are widely studied for their effects on
      cell movement, navigation, angiogenesis, immunology and cancer.
      Semaphorins/collapsins were characterized in part on the basis of their ability
      to drastically alter actin cytoskeletal dynamics in neuronal processes, but
      despite considerable progress in the identification of semaphorin receptors and
      their signalling pathways, the molecules linking them to the precise control of
      cytoskeletal elements remain unknown. Recently, highly unusual proteins of the
      Mical family of enzymes have been found to associate with the cytoplasmic portion
      of plexins, which are large cell-surface semaphorin receptors, and to mediate
      axon guidance, synaptogenesis, dendritic pruning and other cell morphological
      changes. Mical enzymes perform reduction-oxidation (redox) enzymatic reactions
      and also contain domains found in proteins that regulate cell morphology.
      However, nothing is known of the role of Mical or its redox activity in mediating
      morphological changes. Here we report that Mical directly links semaphorins and
      their plexin receptors to the precise control of actin filament (F-actin)
      dynamics. We found that Mical is both necessary and sufficient for semaphorin
      plexin-mediated F-actin reorganization in vivo. Likewise, we purified Mical
      protein and found that it directly binds F-actin and disassembles both individual
      and bundled actin filaments. We also found that Mical utilizes its redox activity
      to alter F-actin dynamics in vivo and in vitro, indicating a previously unknown
      role for specific redox signalling events in actin cytoskeletal regulation. Mical
      therefore is a novel F-actin-disassembly factor that provides a molecular conduit
      through which actin reorganization-a hallmark of cell morphological changes
      including axon navigation-can be precisely achieved spatiotemporally in response
      to semaphorins.

PMID- 20148039
TI  - Sudden infant death and co-sleeping: stronger warning needed.

PMID- 20148030
TI  - Genome sequencing and analysis of the model grass Brachypodium distachyon.
AB  - Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae,
      provide the bulk of human nutrition and are poised to become major sources of
      renewable energy. Here we describe the genome sequence of the wild grass
      Brachypodium distachyon (Brachypodium), which is, to our knowledge, the first
      member of the Pooideae subfamily to be sequenced. Comparison of the Brachypodium,
      rice and sorghum genomes shows a precise history of genome evolution across a
      broad diversity of the grasses, and establishes a template for analysis of the
      large genomes of economically important pooid grasses such as wheat. The high
      quality genome sequence, coupled with ease of cultivation and transformation,
      small size and rapid life cycle, will help Brachypodium reach its potential as an
      important model system for developing new energy and food crops.

PMID- 20148040
TI  - Gender inequality in New Zealand life expectancy: decomposition by age and cause.
AB  - AIM To quantify gender inequality in life expectancy at birth (LEB) in New
      Zealand and the contribution to it made by different age groups and causes of
      death. To examine the response of the health sector.METHOD Determination of the
      trend in sex differences in LEB. Multiple decrement decomposition of LEB
      differences into components ages and causes. Review of the gender equity policies
      and priorities of New Zealand's main health sector stakeholders.RESULTS A
      difference between the sexes in LEB of 4.7 years for Maori and 4.0 years for non
      Maori, reverses the historically lower gender disparity among the Maori. Over
      half of the sex difference in LEB is accounted for by heart disease and all types
      of cancer and almost a quarter by accidents and suicide but male survival
      disadvantage is evident in many other causes of death. The health sector is
      beginning to acknowledge the survival disadvantage of men as inequitable, and
      reducing disparity as a legitimate goal for health policy.CONCLUSION Although
      gender inequality in LEB is declining among the non-Maori it remains high among
      the Maori. Smoking habits may explain some of the difference in LEB but policies
      must also address the causes of sex differences in accidental death and suicide.

PMID- 20148041
TI  - Does mortality vary between pacific groups in New Zealand? Estimating Samoan,
      Cook Island Maori, Tongan, and Niuean mortality rates using hierarchical Bayesian
      modelling.
AB  - BACKGROUND Pacific mortality rates are traditionally presented for all Pacific
      people combined, yet there is likely heterogeneity between separate Pacific
      ethnic groups. We aimed to determine mortality rates for Samoan, Cook Island
      Maori, Tongan, and Niuean ethnic groups (living in New Zealand). METHODS We used
      New Zealand Census-Mortality Study (NZCMS) data for 2001-04, for 380,000 person
      years of follow-up of 0-74 year olds in the 2001-04 cohort for which there was
      complete data on sex, age, ethnicity (total counts), natality, and household
      income. Given sparse data, we used hierarchical Bayesian (HB) regression
      modelling, with: a prior covariate structure specified for sex, age, natality
      (New Zealand/Overseas born), and household income; and smoothing of rates using
      shrinkage. The posterior mortality rate estimates were then directly
      standardised.RESULTS Standardising for sex, age, income, and natality, all-cause
      mortality rate ratios compared to Samoan were: 1.21 (95% credibility interval
      1.05 to 1.42) for Cook Island Maori; 0.93 (0.77 to 1.10) for Tongan; and 1.07
      (0.88 to 1.29) for Niuean. Cardiovascular disease (CVD) mortality rate ratios
      showed greater heterogeneity: 1.66 (1.26 to 2.13) for Cook Island Maori; 1.11
      (0.72 to 1.58) for Niuean; and 0.86 (0.58 to 1.20) for Tongan. Results were
      little different standardising for just sex and age. We conducted a range of
      sensitivity analyses about a plausible range of (differential) return migration
      by Pacific people when terminally ill, and a plausible range of census
      undercounting of Pacific people. Our findings, in particular the elevated CVD
      mortality among Cook Island Maori, appeared robust. CONCLUSIONS To our knowledge,
      this project is the first time in New Zealand that clear (and marked in the case
      of CVD) differences in mortality have been demonstrated between different Pacific
      ethnic groups. Future health research and policy should, wherever possible and
      practicable, evaluate and incorporate heterogeneity of health status among
      Pacific people.

PMID- 20148042
TI  - Mum's the word: factors that influenced young adults' participation in the New
      Zealand Meningococcal B immunisation programme.
AB  - AIMS: To identify the factors that influenced young adults (aged 16-19 years)
      when deciding whether or not to be immunised during the MeNZB campaign. METHOD:
      Semi-structured interviews were held with 11 young adults (7 who consented to the
      Meningococcal B immunisation and 4 who did not) to explore their immunisation
      decision. A qualitative descriptive data analysis was then undertaken to reveal
      the latent and manifest themes arising from the interviews. RESULTS: Similar
      influences on the decision-making process were described by all the young adults,
      regardless of the outcome. These included weighing up the risks involved, and
      making collaborative decisions with their families, especially their mothers.
      Situating the decision in a personal context required the young adults to
      consider factors such as needle-phobia, herd immunity, and the accessibility of
      the immunisation. CONCLUSION: The information used in immunisation campaigns
      involving young adults must be carefully balanced so that the situation becomes
      real to the target group, while also helping inform others, especially parents,
      who will be involved in the decision-making process.

PMID- 20148043
TI  - Sero-prevalence of leptospirosis in workers at a New Zealand slaughterhouse.
AB  - AIMS: To undertake a pilot study to measure the sero-prevalence to Leptospira
      serovars Hardjo and Pomona in an occupationally exposed group. To evaluate worker
      age, sex and previous clinical episodes of leptospirosis as risk factors for sero
      positivity. METHODS: A cross-sectional sero-prevalence study was conducted in
      February and March 2008 at a predominantly sheep slaughterhouse in Hawke's Bay,
      New Zealand. A single blood sample was collected from 242 meatworkers, comprising
      145 men and 97 women. Sera were tested by the Microscopic Agglutination Test
      (MAT) with a titre cut point of 1:24, using serovars Pomona and Hardjo as
      antigens. Age, sex, and details of previous clinical episodes of leptospirosis
      were recorded. RESULTS: Overall sero-prevalence was 9.5%. Ten (4.1%) workers were
      positive to serovar Hardjo (titres 1:24-1:192), 13 (5.4%) were positive to
      serovar Pomona (titres 1:24-1:768), and one worker was positive for both
      serovars. Sero-prevalence was 13.1% and 4.1% in men and women, respectively. The
      median age for sero-positive workers was 54 years while that for sero-negative
      workers was 48 years. Twenty-three workers (9.5%) reported a leptospirosis
      disease episode 1-35 years previously, and 14 of those were sero-positive in the
      current study. CONCLUSION: The sero-prevalence observed suggests significant
      exposure to leptospirosis from sheep in meatworkers in the slaughterhouse
      studied. This sero-prevalence was similar to that reported in a survey in 1982.
      Further study is needed to determine the link between sero-prevalence and
      incidence, whether the prevalence of leptospirosis is similar in other
      slaughterhouses, and to develop a better understanding of risk factors important
      for the reduction of exposure of this occupationally acquired disease.

PMID- 20148044
TI  - Acute gastrointestinal illness in New Zealand: information from a survey of
      community and hospital laboratories.
AB  - AIM: To describe and quantify laboratory testing of faecal samples for enteric
      pathogens as a component of the reporting pyramid of acute gastrointestinal
      illness (AGI) in New Zealand. METHOD: Postal survey of community and hospital
      laboratories throughout New Zealand conducted in mid-2006, requesting data from
      the 2005 calendar year. RESULTS: Of the 47 laboratories eligible for the survey,
      responses were received from 35 (74%, 16 hospital laboratories, 12 community
      laboratories, five hospital and community laboratories, and two Public Health
      Laboratories). Based on survey data and extrapolation it was estimated that
      approximately 250,000 faecal samples were received by New Zealand laboratories in
      2005. The majority of these (77%) were requested by primary healthcare providers
      on people in the community. Routine testing of these samples would include
      bacteria (Salmonella, Shigella, Campylobacter, Yersinia) and parasites
      (Cryptosporidium, Giardia) and (depending principally on the age of the patient)
      rotavirus. Testing for other pathogens was comparatively infrequent. The
      frequency of detection of a pathogen in community samples was estimated as
      approximately 20%. CONCLUSION: The positivity rate of 20% for faecal samples from
      people in the community is consistent with overseas results. Although there was
      considerable variation in the testing methods employed by the laboratories the
      methods were considered appropriate based on consultation with ESR Public Health
      and Reference Laboratory staff. These data on the number and type of samples, and
      positivity rate , will assist in the determination of a reporting pyramid for AGI
      in New Zealand.

PMID- 20148045
TI  - 'Party pill' drugs--BZP and TFMPP.
AB  - BZP and TFMPP are amphetamine-like recreational drugs and the major active
      components of 'party pills'. The pharmacodynamic effects of these neurally active
      drugs are thought to be dependent on their activity at DA and 5-HT receptors and
      several studies report drug-drug interactions at a pharmacodynamic level. Their
      metabolism involves the hepatic P450 enzymes CYP2D6, CYP1A2 and CYP3A4 resulting
      in inhibited metabolism of other drugs and medicines, as well as compromised
      metabolism in poor metabolisers for CYP2D6. Basic pharmacokinetic properties are
      described for both BZP and TFMPP when taken alone and in combination. Several
      studies have shown that these drugs cause several drug-drug interactions.

PMID- 20148046
TI  - What is the mechanism of sudden infant deaths associated with co-sleeping?
AB  - The risk of Sudden Infant Death Syndrome (SIDS) has fallen dramatically in the
      "Back to Sleep" era; however, half the cases now occur when the infant has been
      sleeping in bed with another person. Despite the association of SIDS with co
      sleeping, parents are receiving mixed messages. It is often presumed that co
      sleeping deaths are due to 'overlaying', when the adult rolls on top of the baby,
      stopping baby from breathing. We examine research that shows that it is not
      necessary to cover the face, or squash the body of a baby to restrict or prevent
      breathing and cause oxygen deprivation. At birth, the temporo-mandibular joint is
      not yet fully formed, and thus the jaw can be easily displaced upwards and
      backwards pushing the tongue into the upper airway to form a partial or complete
      block of the airway. Indeed, this can happen with firm flexion of the infant's
      head so that the chin pushes against its own chest. Further research is needed,
      but on present evidence, all parents should be advised to sleep their baby in a
      cot or similar next to their parent's bed, until baby is at least 6 months of
      age.

PMID- 20148047
TI  - Will the financial crisis get under the skin and affect our health? Learning from
      the past to predict the future.

PMID- 20148048
TI  - Climate science, denial and the Declaration of Delhi.
AB  - Human-induced climate change is now the central health issue facing humanity. The
      World Medical Association recently adopted the Declaration of Delhi, committing
      the medical profession to mitigate and adapt to the effects of climate change.
      This is new professional territory for many doctors. Even so, the profession has
      often engaged with issues outside 'the health sector' when the stakes are high,
      for example leaded petrol, road safety, tobacco, and nuclear weapons. The
      scientific basis to the declaration merits scrutiny in light of commonly used
      contrary arguments. Decisions in medicine, as elsewhere, must be taken on the
      evidence to hand, weighing up the risks, given that complete knowledge is seldom
      available and time is precious. There are strong analogies between clinical
      experience and our approach to planetary climate. The relevant context for
      scientific observations on climate is the world's multi-gigatonne annual CO2
      equivalent greenhouse gas emissions. Emissions drive changes in concentrations of
      greenhouse gases, which matters when they are rapid or prolonged. The current
      variation in global temperature is alarming, even when within 'normal range'.
      Climate models inform and guide present-day decision-making, and perform well in
      explaining observed warming. They corroborate other evidence that tells us that
      CO2 and other greenhouse gases are harmful at current atmospheric concentrations.
      As a profession and as global citizens, we need to move beyond dissent and denial
      about anthropogenic climate change. The WMA correctly says that circumstances now
      require us all to take action.

PMID- 20148049
TI  - Rectus sheath haematoma: an anticoagulation dilemma.
AB  - Rectus sheath haematoma (RSH) is an uncommon condition with a propensity for
      difficult and mistaken diagnosis. We describe a case where management was
      complicated by the patient's requirement for anticoagulation.

PMID- 20148050
TI  - Incarceration of an umbilical hernia following colonoscopy.
AB  - We describe the unique case of a patient who developed incarceration of a loop of
      small bowel in an umbilical hernia following an uneventful diagnostic
      colonoscopy. It was treated with laparotomy, with release of the incarcerated
      bowel and closure of the defect with nylon sutures.

PMID- 20148051
TI  - Medical image. Hypereosinophilic syndrome with lung involvement.

PMID- 20148052
TI  - The quality of life of New Zealand doctors and medical students: what can be done
      to avoid burnout?
AB  - Life as a doctor or medical student poses particular challenges and stressors
      which can impact on quality of life. This paper sets out to review what is known
      about the quality of life of doctors and medical students and the ramifications
      of a poor quality of life. This paper summarises the national and international
      literature on what is known about quality of life and burnout with regards to
      both medical students and doctors in terms of the origin of these issues and
      various risk factors. This paper further recommends ways of addressing these
      issues from an undergraduate level, for doctors in practice, and then in the
      workplace. It is critical that the New Zealand medical workforce addresses these
      issues in a timely manner. In addition, the paper proposes that if doctors,
      particularly those involved as clinical teachers, have a poor quality of life,
      the learning environment for medical students may be adversely affected.
      Exploration of the evidence around these important issues and their relevance to
      the New Zealand context are considered with suggested solutions.

PMID- 20148053
TI  - Diabetes and tobacco.

PMID- 20148054
TI  - Majority support by Maori and non-Maori smokers for many aspects of increased
      tobacco control regulation: national survey data.

PMID- 20148055
TI  - Protecting victims of domestic violence.

PMID- 20148057
TI  - Rewriting the inverse care law.

PMID- 20148056
TI  - Response to Narasimhan and Clausen's letter on heterophile antibodies and
      troponin results.

PMID- 20148058
TI  - Resource constraint is all the more reason to not let up on inequalities.

PMID- 20148059
TI  - A survey of New Zealand patients' preferred characteristics of their general
      practitioners.

PMID- 20148060
TI  - Intrinsic competition and its effects on the survival and development of three
      species of endoparasitoid wasps.
AB  - In natural systems, pre-adult stages of some insect herbivores are known to be
      attacked by several species of parasitoids. Under certain conditions, hosts may
      be simultaneously parasitised by more than one parasitoid species (=
      multiparasitism), even though only one parasitoid species can successfully
      develop in an individual host. Here, we compared development, survival, and
      intrinsic competitive interactions amongst three species of solitary larval
      endoparasitoids, Campoletis sonorensis (Cameron) (Hymenoptera: Ichneumonidae),
      Microplitis demolitor Wilkinson, and Microplitis croceipes (Cresson)
      (Hymenoptera: Braconidae), in singly parasitised and multiparasitised hosts. The
      three species differed in certain traits, such as in host usage strategies and
      adult body size. Campoletis sonorensis and M. demolitor survived equally well to
      eclosion in two host species that differed profoundly in size, Pseudoplusia
      includens (Walker) and the larger Heliothis virescens (Fabricius) (both
      Lepidoptera: Noctuidae). Egg-to-adult development time in C. sonorensis and M.
      demolitor also differed in the two hosts. Moreover, adult body mass in C.
      sonorensis (and not M. demolitor) was greater when developing in H. virescens
      larvae. We then monitored the outcome of competitive interactions in host larvae
      that were parasitised by one parasitoid species and subsequently multiparasitised
      by another species at various time intervals (0, 6, 24, and 48 h) after the
      initial parasitism. These experiments revealed that M. croceipes was generally a
      superior competitor to the other two species, whereas M. demolitor was the
      poorest competitor, with C. sonorensis being intermediate in this capacity.
      However, competition sometimes incurred fitness costs in M. croceipes and C.
      sonorensis, with longer development time and/or smaller adult mass observed in
      surviving wasps emerging from multiparasitised hosts. Our results suggest that
      rapid growth and large size relative to competitors of a similar age may be
      beneficial in aggressive intrinsic competition.

PMID- 20148061
TI  - Short and Long-Term Incidence of Tuberculosis and CD4-Cell Count Dynamic on HAART
      in Senegal.
AB  - OBJECTIVES: Estimate tuberculosis (TB) incidence among patients receiving HAART.
      Compare the dynamic of the CD4-cell count and viral load before notification of
      the TB with the dynamic among patients remaining free of TB. DESIGN: Prospective
      cohort with ascertainment of TB cases from medical records. METHODS: The first
      404 adults HIV-1 infected patients enrolled in the Senegalese antiretroviral drug
      access initiative were eligible. CD4-cell and viral load were assessed at
      baseline and every 6 months. Patients receiving an antituberculosis treatment at
      HAART initiation were excluded from analysis. Any TB case notified after the
      first month of HAART was considered as an incident case. Follow-up was censored
      at death or at the last visit before March 31, 2008. CD4-cell trajectories until
      TB notification were compared to non-TB developers within two distinct periods:
      from HAART initiation to 24 months and after. RESULTS: Over 404 eligible
      patients, 352 were included in this analysis. Median follow-up reached 73 months
      and 1821 person-years were accrued. Half of the 42 incident cases were notified
      before month 19 of HAART yielding to an overall incident rate of 2.3/100 PY [1.7
      3.1]. Annual incidence decreased with duration of HAART (trend in incidence:
      RR=0.26, p<10(-4)). During the first period, CD4-cell count dynamic of most TB
      patients was identical to the dynamic among patients remaining free of TB. Most
      cases of the second period occurred in a context of an immunological failure.
      CONCLUSIONS: This study provides an estimate of TB incidence among patients on
      HAART in Senegal and supports two underlying mechanisms.

PMID- 20148062
TI  - DISTq: An Iterative Analysis of Glucose Data for Low-Cost, Real-Time and Accurate
      Estimation of Insulin Sensitivity.
AB  - Insulin sensitivity (SI) estimation has numerous uses in medical and clinical
      situations. However, highresolution tests that are useful for clinical diagnosis
      and monitoring are often too intensive, long and costly for regular use. Simpler
      tests that mitigate these issues are not accurate enough for many clinical
      diagnostic or monitoring scenarios. The gap between these tests presents an
      opportunity for new approaches. The quick dynamic insulin sensitivity test
      (DISTq) utilises the model-based DIST test protocol and a series of population
      estimates to eliminate the need for insulin or C-peptide assays to enable a high
      resolution, low-intensity, real-time evaluation of SI. The method predicts
      patient specific insulin responses to the DIST test protocol with enough accuracy
      to yield a useful clinical insulin sensitivity metric for monitoring of diabetes
      therapy. The DISTq method replicated the findings of the fully sampled DIST test
      without the use of insulin or C-peptide assays. Correlations of the resulting SI
      values was R=0.91. The method was also compared to the euglycaemic
      hyperinsulinaemic clamp (EIC) in an in-silico Monte-Carlo analysis and showed a
      good ability to re-evaluate SI(EIC) (R=0.89), compared to the fully sampled DIST
      (R=0.98) Population-derived parameter estimates using a-posteriori population
      based functions derived from DIST test data enables the simulation of insulin
      profiles that are sufficiently accurate to estimate SI to a relatively high
      precision. Thus, costly insulin and C-peptide assays are not necessary to obtain
      an accurate, but inexpensive, real-time estimate of insulin sensitivity. This
      estimate has enough resolution for SI prediction and monitoring of response to
      therapy. In borderline cases, re-evaluation of stored (frozen) blood samples for
      insulin and C-peptide would enable greater accuracy where necessary, enabling a
      hierarchy of tests in an economical fashion.

PMID- 20148063
TI  - Nocardiosis in a kidney-pancreas transplant.
AB  - 34-year-old man with chronic renal and pancreas failure in complicated diabetic
      disease received a kidney-pancreas transplantation. On the 32nd postoperative
      day, an acute kidney rejection occurred and resolved with OKT3 therapy. The
      patient also presented refractory urinary infection by E. Fecalis and M.
      Morganii, and a focal bronchopneumonia in the right-basal lobe resolved with
      elective chemotherapy. During the 50th post-operative day, an intense soft tissue
      inflammation localized in the first left metatarsal-phalangeal articulation
      occurred (Figure 1) followed by an abscess with a cutaneous fistula and extension
      to the almost totality of foot area. The radiological exam revealed a small osteo
      lacunar image localized in the proximal phalanx head of the first finger foot.
      From the cultural examination of the purulent material, N. Asteroides was
      identified. An amoxicillin-based treatment was started and continued for three
      months, with the complete resolution of infection This case is reported for its
      rarity in our casuistry, and for its difficult differential diagnosis with other
      potentially serious infections.

PMID- 20148064
TI  - Long-Term Alendronate Use Not without Consequences?
AB  - A previously unknown side effect of biphosphonate use is emerging. In a specific
      patient group on long term biphosphonate therapy stress femur fractures seem to
      occur. The typical presentation consists of prodromal pain in the affected leg
      and/or a discrete cortical thickening on the lateral side of the femur in
      conventional radiological examination or the presentation with a spontaneous
      transverse subtrochanteric femur with typical features. We present three cases of
      this stress fracture in patients on bisphosphonate therapy. One of these patients
      suffered a bilateral femur fracture of the same type. In our opinion, in patients
      on bisphosphonate therapy who present with a spontaneous femur fracture, seizing
      therapy is advisable. In bilateral cases preventive nailing should be considered.

PMID- 20148065
TI  - The Impact of Intervention on Sexual Practices of HIV Positive Individuals in
      Southeast Nigeria.
AB  - Objective. To describe the impact of repeating behavioral educational
      intervention on sexual practices of HIV positive individuals. Method. A
      prospective cohort study of HIV positive individual was conducted in southeast
      Nigeria from June 2007 to May 2008. Information on sexual practices was collected
      at initial visit; education was given and its impact was evaluated afterwards.
      Results. Knowledge about risk of unprotected intercourse increased by 41%, condom
      use by 27% (P < .001) and consistent condom use by 55% (P < .001). The
      significant predictors of consistent condom use include male gender, multiple
      sexual partner, as well as good knowledge of HIV transmission, higher educational
      status and being married. Non use of condom at postintervention survey were
      characterized by female gender (n = 4), monogamous relationship (n = 10), little
      or no education (n = 10), and unmarried (n = 7) respondents. Conclusion. Repeated
      behavioral education intervention improves consistent condom use among HIV
      positive individuals and will help curb the spread of HIV/AIDS.

PMID- 20148066
TI  - The application of restriction landmark genome scanning method for surveillance
      of non-mendelian inheritance in f(1) hybrids.
AB  - We analyzed inheritance of DNA methylation in reciprocal F(1) hybrids (subsp.
      japonica cv. Nipponbare x subsp. indica cv. Kasalath) of rice (Oryza sativa L.)
      using restriction landmark genome scanning (RLGS), and detected differing RLGS
      spots between the parents and reciprocal F(1) hybrids. MspI/HpaII restriction
      sites in the DNA from these different spots were suspected to be heterozygously
      methylated in the Nipponbare parent. These spots segregated in F(1) plants, but
      did not segregate in selfed progeny of Nipponbare, showing non-Mendelian
      inheritance of the methylation status. As a result of RT-PCR and sequencing, a
      specific allele of the gene nearest to the methylated sites was expressed in
      reciprocal F(1) plants, showing evidence of biased allelic expression. These
      results show the applicability of RLGS for scanning of non-Mendelian inheritance
      of DNA methylation and biased allelic expression.

PMID- 20148067
TI  - Extended durability of a cloth-covered star-edwards caged ball prosthesis in
      aortic position.
AB  - The Starr-Edwards caged ball valve is one of the oldest cardiac valve prosthesis
      and was widely used all around the world in the past decades. Despite the long
      term results that have been reported there are only a few cases reported that
      exceed 30 years of durability. Here in, we report a 53-year-old patient with a
      well-functioning 35-year-old aortic Starr-Edwards caged ball prosthesis.

PMID- 20148068
TI  - Controversies on rituximab therapy in sjogren syndrome-associated
      lymphoproliferation.
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disease characterized by chronic
      inflammation of salivary and lachrymal glands, and frequently accompanied by
      systemic symptoms. A subgroup of SS patients develops malignant B cell non
      Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT)
      type and very often located in the major salivary glands. Currently, there is a
      lack of evidence-based intervention therapy which may influence SS-related
      chronic inflammation and lymphoproliferation. B cells are involved in the
      pathogenesis of SS, and B cell downregulation may lead to a decrease of disease
      activity. Rituximab (RTX), a chimeric monoclonal antibody targeting the CD20
      antigen on the B cell surface, has been successfully investigated in other
      autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus,
      ANCA-associated vasculitis, and mixed cryoglobulinemic syndrome. Preliminary
      experiences of RTX therapy in SS patients with or without a lymphoproliferative
      disorder suggest that SS patients with more residual exocrine gland function
      might better benefit from RTX. Efficacy of RTX in SS-associated B-cell lymphoma,
      mainly in low-grade salivary gland lymphomas, remains an open issue.

PMID- 20148069
TI  - Recombinant Activated Factor VII (rFVIIa) in the Management of Major Obstetric
      Haemorrhage: A Case Series and a Proposed Guideline for Use.
AB  - Major obstetric haemorrhage remains a significant cause of maternal morbidity and
      mortality. Previous case reports suggest the potential benefit of recombinant
      activated factor VII (rFVIIa: NovoSeven(R)) as a haemostatic agent. We performed
      a retrospective review of the use of rVIIa in major obstetric haemorrhage in the
      Northern Region between July 2004 and February 2007. Fifteen women received
      rFVIIa. The median patient age was 34 years. Major haemorrhage occurred
      antepartum (5 patients), intrapartum (1), and postpartum (9). All women received
      an initial dose of 90 mcg/kg rFVIIa and one received 2 further doses. Bleeding
      stopped or decreased in 12 patients (80%). Additional measures included
      antifibrinolytic and uterotonic agents, Rusch balloon insertion, uterine
      curettage/packing, and vessel embolisation. Eight patients required hysterectomy.
      All women survived to discharge from hospital. No adverse events, including
      thrombosis, were recorded. This study provides further support for the safety and
      efficacy of rFVIIa as adjunct therapy in major obstetric haemorrhage.

PMID- 20148070
TI  - Land-Jump Performance in Patients with Juvenile Idiopathic Arthritis (JIA): A
      Comparison to Matched Controls.
AB  - Objective. The purpose of this study was to determine if high functioning
      children with Juvenile Idiopathic Arthritis (JIA) with minimal disease activity
      have different biomechanics during high loading tasks compared to controls.
      Patients were included if they had minimal inflammation documented in one or both
      knees. Methods. The subject groups consisted of eleven patients with JIA and
      eleven sex, age, height, and weight matched controls. Sagittal plane kinematic
      and kinetics were calculated during a drop vertical jump maneuver. The Child
      Health Assessment Questionnaire (CHAQ) was collected on each patient with JIA.
      Results. The subjects with JIA had increased knee (P = .011) and hip flexion (P <
      .001) compared to control subjects. Subjects with JIA also demonstrated decreased
      knee extensor moments during take-off (P = .028) and ankle plantar flexor moments
      during landing (P = .024) and take-off (P = .004). In the JIA group, increased
      hip extensor moments were predictive of increased disability (R(2) = .477, SEE =
      .131). Conclusions. Patients with JIA may demonstrate underlying biomechanical
      deviations compared to controls. In addition, biomechanical assessment of hip
      extensor mechanics during dynamic tasks may provide an objective assessment tool
      to determine overall function in patients with JIA.

PMID- 20148072
TI  - Adult Living Donor Liver Transplantation with ABO-Incompatible Grafts: A German
      Single Center Experience.
AB  - Adult living donor liver transplantations (ALDLTs) across the ABO blood group
      barrier have been reported in Asia, North Americas, and Europe, but not yet in
      Germany. Several strategies have been established to overcome the detrimental
      effects that are attached with such a disparity between donor and host, but no
      gold standard has yet emerged. Here, we present the first experiences with three
      ABO-incompatible adult living donor liver transplantations in Germany applying
      different immunosuppressive strategies. Four patient-donor couples were
      considered for ABO-incompatible ALDLT. In these patients, resident ABO blood
      group antibodies (isoagglutinins) were depleted by plasmapheresis or
      immunoadsorption and replenishment was inhibited by splenectomy and/or B-cell
      targeted immunosuppression. Despite different treatments ALDLT could safely be
      performed in three patients and all patients had good initial graft function
      without signs for antibody-mediated rejection (AMR). Two patients had long-term
      graft survival with stable graft function. We thus propose the feasibility of ABO
      incompatible ALDLT with these protocols and advocate further expansion of ABO
      incompatible ALDLT in multicenter trials to improve efficacy and safety.

PMID- 20148071
TI  - Endometrial cancer: what is new in adjuvant and molecularly targeted therapy?
AB  - Endometrial cancer is the most common gynaecological cancer in western countries.
      Radiotherapy remains the mainstay of postoperative management, but accumulating
      data show that adjuvant chemotherapy may display promising results after staging
      surgery. The prognosis of patients with metastatic disease remains disappointing
      with only one-year survival. Progestins represent an effective option, especially
      for those patients with low-grade estrogen and/or progesterone receptor positive
      disease. Chemotherapy using the combination of paclitaxel, doxorubicin, and
      cisplatin is beneficial for patients with advanced or metastatic disease after
      staging surgery and potentially for patients with early-stage disease and high
      risk factors. Toxicity is a point in question; however, the combination of
      paclitaxel with carboplatin may diminish these concerns. In women with multiple
      medical comorbidities, single-agent chemotherapy may be better tolerated with
      acceptable results. Our increased knowledge of the molecular aspects of
      endometrial cancer biology has paved the way for clinical research to develop
      novel targeted antineoplastic agents (everolimus, temsirolimus, gefitinib,
      erlotinib, cetuximab, trastuzumab, bevacizumab, sorafenib) as more effective and
      less toxic options. Continued investigation into the molecular pathways of
      endometrial cancer development and progression will increase our knowledge of
      this disease leading to the discovery of novel, superior agents.

PMID- 20148073
TI  - Aberrant Expression of Critical Genes during Secondary Cell Wall Biogenesis in a
      Cotton Mutant, Ligon Lintless-1 (Li-1).
AB  - Over ninety percent of the value of cotton comes from its fiber; however, the
      genetic mechanisms governing fiber development are poorly understood. Due to
      their biochemical and morphological diversity in fiber cells cotton fiber mutants
      have been useful in examining fiber development; therefore, using the Ligon
      Lintless (Li-1) mutant, a monogenic dominant cotton mutant with very short
      fibers, we employed the high throughput approaches of microarray technology and
      real time PCR to gain insights into what genes were critical during the secondary
      cell wall synthesis stage. Comparative transcriptome analysis of the normal TM-1
      genotype and the near isogenic Li-1 revealed that over 100 transcripts were
      differentially expressed at least 2-fold during secondary wall biogenesis,
      although the genetic profile of the expansion phase showed no significant
      differences in the isolines. Of particular note, we identified three candidate
      gene families-expansin, sucrose synthase, and tubulin-whose expression in Li-1
      deviates from normal expression patterns of its parent, TM-1. These genes may
      contribute to retarded growth of fibers in Li-1 since they are fiber-expressed
      structural and metabolic genes. This work provides more details into the
      mechanisms of fiber development, and suggests the Li gene is active during the
      later stages of fiber development.

PMID- 20148074
TI  - Improvement of EEG signal acquisition: an electrical aspect for state of the art
      of front end.
AB  - The aim of this study is to present some practical state-of-the-art
      considerations in acquiring satisfactory signals for electroencephalographic
      signal acquisition. These considerations are important for users and system
      designers. Especially choosing correct electrode and design strategy of the
      initial electronic circuitry front end plays an important role in improving the
      system's measurement performance. Considering the pitfalls in the design of
      biopotential measurement system and recording session conditions creates better
      accuracy. In electroencephalogram (EEG) recording electrodes, system electronics
      including filtering, amplifying, signal conversion, data storing, and
      environmental conditions affect the recording performance. In this paper, EEG
      electrode principles and main points of electronic noise reduction methods in EEG
      signal acquisition front end are discussed, and some suggestions for improving
      signal acquisition are presented.

PMID- 20148075
TI  - Gallbladder agenesis and cystic duct absence in an adult patient diagnosed by
      magnetic resonance cholangiography: report of a case and review of the
      literature.
AB  - Gallbladder agenesis (GA) is a rare congenital anomaly of the biliary system
      often associated with other congenital abnormalities. Patients become symptomatic
      in 23% of cases. GA is often misinterpreted as other diseases, therefore, leading
      to unnecessary surgery. We report a case of congenital GA associated to cystic
      duct absence and a biliary tract abnormality diagnosed by Magnetic Resonance with
      Cholangiopancreatography.

PMID- 20148076
TI  - A pattern analysis of gene conversion literature.
AB  - Gene conversion is an important biological process that involves the transfer of
      genetic (sequence) information from one gene to another. This can have a variety
      of effects on an organism, both short-term and long-term and both positive and
      detrimental. In an effort to better understand this process, we searched through
      over 3,000 abstracts that contain research on gene conversions, tagging the
      important data and performing an analysis on what we extract. Through this we
      established trends that give a better insight into gene conversion research and
      genetic research in general. Our results show the importance of the process and
      the importance of continuing gene conversion research.

PMID- 20148077
TI  - Long-term outcomes in a family with nephrogenic syndrome of inappropriate
      antidiuresis.
AB  - We report a familial case of the nephrogenic syndrome of inappropriate
      antidiuresis (NSIAD), including 30-year followup data on two patients. The
      proband and one maternal uncle presented in their infancy with severe recurrent
      hyponatremia, and clinical pictures consistent with the syndrome of inappropriate
      antidiuretic hormone (SIADH) in the absence of an elevated ADH level. They were
      both confirmed to be hemizygous for the R137C mutation on the V2R gene (AVPR2),
      the same locus of the gain of function mutation demonstrated in the original
      reports of this condition. The proband's mother was identified as an asymptomatic
      carrier of this X-linked condition. Our case describes a favourable long-term
      outcome for NSIAD, in particular, successful treatment with oral urea during the
      infancy period, and with self-regulated precautions on fluid intake into adult
      life.

PMID- 20148078
TI  - Studies of the suitability of fowlpox as a decontamination and thermal stability
      simulant for variola major.
AB  - Variola major, the causative agent of smallpox, has been eradicated from nature.
      However, stocks still exist; thus, there is a need for relevant decontamination
      studies, preferably with nonpathogenic simulants. Previous studies have shown a
      similarity in response of vaccinia virus and variola major to various
      decontaminants and thermal inactivation. This study compared vaccinia and fowlpox
      viruses under similar conditions, using disinfectants and temperatures for which
      variola major data already existed. Most disinfectants showed similar efficacy
      against vaccinia and fowlpox, suggesting the utility of fowlpox as a
      decontamination simulant. Inactivation kinetics studies showed that fowlpox
      behaved similarly to variola major when treated with 0.1% iodine and 5.7%
      polyethyleneglycol nonylphenyl ether, 0.025% sodium hypochlorite, 0.05% sodium
      hypochlorite, and 0.1% cetyltrimethylammonium chloride and 0.05% benzalkonium
      chloride, but differed in its response to 0.05% iodine and 0.3%
      polyethyleneglycol nonylphenyl ether and 40% ethanol. Thermal inactivation
      studies demonstrated that fowlpox is a suitable thermal simulant for variola
      major between 40 degrees C and 55 degrees C.

PMID- 20148080
TI  - The importance of saccular function to motor development in children with hearing
      impairments.
AB  - Children with hearing deficits frequently have delayed motor development. The
      purpose of this study was to evaluate saccular function in children with hearing
      impairments using the Vestibular Evoked Myogenic Potential (VEMP). The impact of
      the saccular hypofunction on the timely maturation of normal balance strategies
      was examined using the Movement Assessment Battery for Children (Movement ABC).
      Thirty-three children with bilateral severe/profound hearing impairment between 4
      and 7 years of age were recruited from a three-state area. Approximately half of
      the sample had one or bilateral cochlear implants, one used bilateral hearing
      aids, and the rest used no amplification. Parents reported whether the hearing
      impairment was diagnosed within the first year or after 2 years of age. No VEMP
      was evoked in two thirds of the hearing impaired (HI) children in response to the
      bone-conducted stimulus. Children who were reportedly hearing impaired since
      birth had significantly poorer scores when tested with the Movement ABC.

PMID- 20148079
TI  - Vitamin d deficiency in cystic fibrosis.
AB  - Cystic Fibrosis is the most common inherited genetic respiratory disorder in the
      Western World. Hypovitaminosis D is almost universal in CF patients, likely due
      to a combination of inadequate absorption, impaired metabolism, and lack of sun
      exposure. Inadequate levels are associated with the high prevalence of bone
      disease or osteoporosis in CF patients, which is associated with increased
      morbidity including fractures, kyphosis, and worsening pulmonary status.
      Treatment goals include regular monitoring 25 hydroxyvitamin D (25OHD) levels
      with aggressive treatment for those with levels <75 nmol/L (<30 ng/mL). More
      research is needed to determine optimal supplementation goals and strategies.

PMID- 20148081
TI  - Novel influenza H1N1 in pregnancy: a report of two cases.
AB  - BACKGROUND: Pregnant women are a high-risk group for morbidity and mortality from
      influenza. During the current pandemic of H1N1 influenza, few cases of H1N1 have
      been reported in pregnancy. CASES: We report two cases of H1N1 influenza which
      occurred in single institution in the course of one month. The first patient
      developed acute respiratory distress syndrome, required intubation, and
      eventually died. The second patient had influenza H1N1 that did not have any
      major sequela. CONCLUSION: H1N1 influenza in pregnancy can be associated with
      severe complications. Widespread vaccination, when available, prompt diagnosis,
      and adequate treatment with antiviral medications when infection occurs are
      required.

PMID- 20148082
TI  - Adsorption of Pb(II) and Cd(II) by Squid Ommastrephes bartrami Melanin.
AB  - The adsorption of Cd(II) and Pb(II) by squid melanin was investigated. At a metal
      ion concentration of 2 mM/L, the biosorption efficiency of melanin reached 95%
      for Cd(II) and Pb(II). The maximum content of bound Cd(II) and Pb(II) was 0.93
      mM/g and 0.65 mM/g, respectively. Temperature had no obvious effect on the
      adsorption of the metals, and in a pH range of 4.0-7.0, the adsorption yield was
      high and stable. Macrosalts such as NaCl, MgCl(2), and CaCl(2) had no obvious
      effect on the binding of Pb(II) but greatly diminished the adsorption of Cd(II),
      which indicated that different functional groups in squid melanin are responsible
      for their adsorption. IR analysis of metal ion-enriched squid melanin
      demonstrated that the possible functional groups responsible for metal binding
      were phenolic hydroxyl (OH), carboxyl (COOH), and amine groups (NH). This study
      reports a new material for the removal of heavy metals from low-strength
      wastewater.

PMID- 20148084
TI  - Long-term outcomes following hepatic resection and radiofrequency ablation of
      colorectal liver metastases.
AB  - Recently some have called for randomized controlled trials comparing RFA to
      hepatic resection, particularly for patients with only a few small metastases.
      The objectives were to compare local recurrence and survival following RFA and
      hepatic resection for colorectal liver metastases. This was a retrospective
      review of open RFA and hepatic resection for colorectal liver metastases between
      January 1998 and May 2007. All patients who had RFA were considered to have
      unresectable disease. 58 patients had hepatic resection and 43 had RFA. A 5-year
      survival after resection was 43% compared to 23% after RFA. For patients with
      solitary lesions, a 5-year survival was 48% after resection and 15% after RFA.
      Sixty percent of patients suffered local recurrences after RFA compared to 7%
      after hepatic resection. RFA is inferior to resection. The results observed in
      this study support the consensus that RFA cannot be considered an equivalent
      procedure to hepatic resection.

PMID- 20148085
TI  - Reproducible RNA preparation from sugarcane and citrus for functional genomic
      applications.
AB  - High-throughput functional genomic procedures depend on the quality of the RNA
      used. Copurifying molecules can negatively impact the functionality of some plant
      RNA preparations employed in these procedures. We present a simplified, rapid,
      and scalable SDS/phenol-based method that provides the high-quantity and -quality
      RNA required by the newly emerging biotechnology applications. The method is
      applied to isolating RNA from tissues of two biotechnologically important crop
      plants, sugarcane and citrus, which provide a challenge due to the presence of
      fiber, polysaccharides, or secondary metabolites. The RNA isolated by this method
      is suitable for several downstream applications including northern blot
      hybridization, microarray analysis, and quantitative RT-PCR. This method has been
      used in a diverse range of projects ranging from screening plant lines
      overexpressing mammalian genes to analyzing plant responses to viral infection
      and defense signaling molecules.

PMID- 20148083
TI  - The roles of streptozotocin neurotoxicity and neutral endopeptidase in murine
      experimental diabetic neuropathy.
AB  - We demonstrated that inhibition of neutral endopeptidase (NEP), a protease that
      degrades vaso- and neuroactive peptides, improves vascular and neural function in
      diabetic animal models. In this study we explored the role of NEP in neuropathy
      related to either insulin-deficient diabetes or diet-induced obesity using NEP
      deficient (-/-) mice. Initial studies showed that streptozotocin, in the absence
      of subsequent hyperglycemia, did not induce nerve conduction slowing or paw
      thermal hypoalgesia. Glucose disposal was impaired in both C57Bl/6 and NEP -/-
      mice fed a high fat diet. Thermal hypoalgesia and nerve conduction slowing were
      present in both streptozotocin-diabetic and high fat fed C57Bl/6 mice but not in
      NEP -/- mice exposed to either streptozotocin-induced diabetes or a high fat
      diet. These studies suggest that streptozotocin does not induce neurotoxicity in
      mice and that NEP plays a role in regulating nerve function in insulin-deficient
      diabetes and diet-induced obesity.

PMID- 20148086
TI  - Phenotypic and Genotypic Characterization of Staphylococcus aureus Strains from
      Italian Dairy Products.
AB  - Staphylococcus aureus is a known major cause of foodborne illnesses, and milk and
      dairy products are often contaminated by enterotoxigenic strains of this
      bacterium. In the present study, 122 S. aureus isolates collected from different
      dairy products were characterised by phenotypic properties, by the distribution
      of genes encoding staphylococcal enterotoxins (sea, sec, sed, seg, seh, sei, sej,
      and sel) and by randomly amplified polymorphic DNA PCR (RAPD-PCR). Moreover,
      strain resistance to vancomycin and methicillin (oxacillin) was studied. The
      differences in the RAPD-PCR profiles obtained with the primers M13 and AP4
      revealed the presence of a great genetic heterogeneity among the different S.
      aureus strains. Using the primer AP4 and M13, eight groups were distinguished by
      RAPD-PCR cluster analysis, although, except in few cases, it was not possible to
      correlate the isolates of different animal species (cow or ovine) with the
      presence of se genes. None of the isolates showed resistance to vancomycin or
      methicillin.

PMID- 20148088
TI  - Achieving a dream: meeting policy goals related to improving drug access.
AB  - International experts recognize that significant inequities exist in the
      accessibility of life-saving medicines among poor and vulnerable populations,
      especially in developing countries. This article highlights that drug access even
      for relatively cheap medicines is out of reach for the vast numbers of global
      poor. This badly affects people living with HIV/AIDS who face serious obstacles
      in accessing ARVs. The same concerns are attributed to neglected diseases.
      Despite international meetings, promises from the pharmaceutical industry and a
      lot of media attention little has changed in the past 20 years. The accessibility
      gap to life-saving drugs could be reduced by the UNITAID initiative to pool
      patents for the many different ARVs, but the reality is that UNITAID is still a
      promise. To surmount this global problem of inequity requires a rethinking of
      traditional models of drug access and health objectives that should not be
      compromised by commercial interests.

PMID- 20148089
TI  - Antiretroviral (ARV) Therapy in Resource Poor Countries: What do we Need in Real
      Life?
AB  - Significant progresses have been made in the last 5 years towards the ultimate
      goal to provide universal access to care for all HIV/AIDS patients needing
      antiretroviral treatment in resource-poor countries. However, many barriers are
      still to be overcome, including () cost of care for the individual, () stigma, ()
      lack of qualified human resources and infrastructure, especially in the rural
      setting, () rescue drugs for failing patients and () pediatric formulations.
      Priority actions to be promoted if the fight against HIV/AIDS is to be successful
      include: (i) promoting access to care in the rural areas, (ii) strengthening of
      basic health infrastructures, (iii) waiving of users' fee to get ARV, (iv) a
      larger variety of drugs, with particular regard to fixed dose combination third
      line drugs and pediatric formulations, (v) local quality training and (vi) high
      quality basic and translational research. While the universal access to HIV care
      is crucial in developing countries, a strong emphasis on prevention should be
      maintained along.

PMID- 20148087
TI  - Growth and reproductive outcomes in congenital adrenal hyperplasia.
AB  - The treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency is complex. In addition to disease control, important therapeutic
      goals are the maintenance of normal growth and the acquisition of normal
      reproductive function. Here, data regarding final adult height (FH) in patients
      with CAH will be reviewed. Additional difficulties associated with CAH, including
      risks of obesity and hypertension, will be discussed. Information about fertility
      and reproductive outcomes in men and women with CAH will also be summarized.
      Although the treatment of each child with CAH needs to be individualized, close
      medical followup and laboratory monitoring along with good compliance can often
      result in positive clinical outcomes.

PMID- 20148090
TI  - Towards a Patent Pool for HIV Medicines: The Background.
AB  - Recent WHO guidelines for antiretroviral therapy recommend switching to less
      toxic, but more expensive medicines for first-line and second-line ART, raising
      questions about the financial sustainability of many AIDS treatment programmes.
      At the same time, many key generic producing countries such as India now grant
      pharmaceutical product patents so competition between multiple manufacturers will
      not be able to play the role it has in bringing down the price of newer
      drugs.Overcoming these patent barriers will require a range of solutions, such as
      restricting patentability criteria, or compulsory licensing. One additional
      systematic solution is provided by the patent pool, a collective solution to the
      management of patent rights, initially presented by Medecins Sans Frontieres to
      the French Foreign Ministry and subsequently the UNITAID Executive Board in
      2006.A patent pool must not be implemented at any costs, but answer medical
      needs, be based on economic realities and meet the access needs of the developing
      world, including middle-income countries.

PMID- 20148091
TI  - Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) - A Strategic
      Option for India.
AB  - The current HIV/AIDS scenario in India is quite grim with an estimated 2.4
      million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and
      Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS
      treatment. Over 30 ARVs (single and FDCs) available under six categories viz.,
      NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside
      reverse transcriptase inhibitors), Protease inhibitors, the new Fusion
      inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase
      strand transfer inhibitors. The major originator companies for these ARVs are:
      Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead,
      GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with
      zidovidine in 1987, all the drugs are available in the developed countries. In
      India, about 30 ARVs are available as generics manufactured by Aurobindo,
      Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune,
      Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals,
      Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal
      Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control
      Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to
      HIV positive patients in India since 2004. The drugs available in India include
      both single drugs and FDCs covering both first line and second line ARVs. Even
      while there are claims of stabilization of the disease load, there is still huge
      gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from
      the Govt. and other sources. Access to ARVs therefore is still a cause of serious
      concern ever since India became fully Trade Related Aspects of Intellectual
      Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical
      companies cannot make generics for those for drugs introduced post-2005 due to
      product patent regime. Other concerns include heat stable, other better
      formulations and second line ARVs for adults and more drugs and formulations for
      paediatric groups, that are still to be widely available in India and other
      developing countries. To examine whether strong intellectual property (IP)
      protection systems are to be considered important barriers for the limited or
      lack of access to ARVs, we studied the patent profile of the ARVs of the
      originator companies within and outside India. We could record 93 patents in the
      United States Patent & Trademark Office (USPTO). The originator companies have
      been also aggressively filing and enforcing patents in India. There have been a
      few efforts by companies like Gilead and GSK to grant licenses to generic
      manufacturers in developing countries, ostensibly to promote access to ARVs
      through lower (two-tier) pricing. These steps are considered as too little and
      too late. There is an urgent need to look for alternative strategies to promote
      access to ARVs both linked to and independent of IPRs. Patent pooling as a viable
      strategy mooted by the UNITAID should be seriously explored to promote access to
      ARVs. India is ideally suited for trying out the patent pool strategy as most of
      the global requirement of affordable ARV drugs for HIV/AIDS treatment is sourced
      from Indian generic companies.

PMID- 20148092
TI  - Patent Pools for ARVs: Industry Perspectives from ASPEN.
AB  - AFFORDABILITY THROUGH REDUCED PRICING IS ONLY ONE PART OF ENHANCING ACCESS TO
      TREATMENT IN PUBLIC HEALTH EMERGENCIES: Supply Security and the guarantee of
      supply consistency is the other. To the extent that Patent Pooling is able to
      create Regional African Manufacturing capability, Africans will support the
      concept. However, to the extent that if further decentralises manufacture away
      from the continent and increases Africa's dependence on imports, Patent Pooling
      can potentially weaken supply security and will continue to relegate Africa a
      Continent of dependency, rather than one that invests in its own capability.
      Patent Pooling, should be viewed guardedly on the African Continent and will only
      be embraced, provided it is consistent with the AU Heads of State call for an
      African Manufacturing Plan and Africa's aspiration to more from "converting
      charity dollars into sustainable, long term investment dollars".

PMID- 20148093
TI  - The dose-response effect of medical exercise therapy on impairment in patients
      with unilateral longstanding subacromial pain.
AB  - OBJECTIVES: The primary aim of this study was to investigate the effect of
      medical exercise therapy in shoulder impingement patients, along with possible
      correlations between impairment variables. STUDY DESIGN: A prospective unblended
      randomized clinical trial. METHODS: Over four months, 61 participants were
      randomly assigned into a high-graded exercise therapy group (HD) (n=31) and into
      a low-graded exercise therapy group (LD) (n=30). Prognostic variables were
      similar between the groups at baseline. Five (8%) patients dropped out during the
      treatment period, and another four (6%) dropped out before followup. Pain was a
      composite score of a visual analogue scale (VAS). Isometric strength was measured
      during four resisted break tests on the shoulder. Function was measured by means
      of a functional assessment questionnaire (Shoulder Rating Questionnaire, SRQ).
      Both groups trained three times per week for twelve weeks, with tests pre- and
      posttraining and six months follow-up. RESULTS: The HD group achieved
      significantly (p < 0.05) better outcome effects than the LD group for pain, range
      of motion, isometric functional strength and function, but both groups increased
      function from pretest to posttest. CONCLUSIONS: In patients with uncomplicated
      subacromial pain syndrome, medical exercise therapy is an efficient treatment
      alternative, where high-grade doses should be emphasized. A major limitation is
      that the measurements were not undertaken by another person than the treating
      physiotherapists.

PMID- 20148094
TI  - Spanish experience in autologous chondrocyte implantation.
AB  - INTRODUCTION: The Spanish Ministry of Health commissioned the Galician Agency for
      Health Technology Assessment to monitor and follow-up Autologous Chondrocyte
      Implantation (ACI) used to treat chondral lesions of the knee in Spain. The
      objective of this monitoring was to assess efficacy and safety of the technique.
      DESIGN: One-hundred and eleven consecutive patients with knee chondral lesions
      were included in a multi-center study between January 2001 and January 2005. ACI
      was used in these patients as a second-line treatment option (or a first-line
      treatment option if the cause was Osteocondritis dissecans). The Cincinnati score
      and the Short Form 36 (SF-36) questionnaire were used to assess the patients'
      self-reported satisfaction with the outcomes of ACI. A descriptive analysis was
      performed and non-parametric tests were used to establish correlations and
      compare results among subgroups. A multivariate analysis was also performed to
      measure the effect of different variables on changes in the condition of the
      knee. RESULTS: Eighty men (72%) and 31 women (21%) with an age range from 16 to
      49 years, underwent ACI surgery. Among these subjects, the most common previous
      first-line treatment was debridement (64 individuals, 74.4%). The mean size of
      the lesion treated with ACI was 3.82 cm(2), and the most frequent location of the
      lesion was the inner femoral condyle (53.6%). The patient satisfaction was high
      or very high in 36 subjects (66.7%). Overall knee joint assessment improved from
      4.32 points to 6.78. All SF-36 questionnaire categories improved, notably those
      related to physical condition. CONCLUSIONS: The results of this study indicate
      that ACI is safe; however, further studies are mandated to assess the efficacy of
      ACI compared to alternative treatment options.

PMID- 20148095
TI  - Surgical management of cervical spondyloarthropathy in hemodialysis patients.
AB  - Dialysis-related spondyloarthropathy is a rare cause of spinal deformity and
      cervical myelopathy. Optimal management of cervical spine spondyloarthropathy
      often requires circumferential reconstructive surgery, because affected patients
      typically have both the anterior column and the facet joints compromised. The
      occasional presence of noncontiguous or "skip lesions" adds an additional level
      of complexity to surgical management, because decompression and fusion in an
      isolated segment of neural compression can worsen spine deformity by applying
      increased stress to adjacent cervical spine segments. We report two cases of
      hemodialysis patients who presented with cervical myelopathy and initially had
      anterior cervical discectomy or corpectomy. Because symptoms recurred due to
      hardware failure, both patients required posterior spine fusion as well. In
      retrospect, because of the hardware failure, both of these patients might have
      benefited from a circumferential (combined anterior and posterior) cervical spine
      reconstruction as their initial treatment.

PMID- 20148096
TI  - The role of different hyaluronic acids in the articular cartilage of rabbit.
AB  - PURPOSE: To elucidate if the differences found in the physico-chemical and
      rheological behaviour of Hyaluronic Acids result in different in vivo activity.
      For this purpose two Hyaluronic Acids (HA), HA-1 and HA-2, with similar molecular
      weight but different percentage of concentration variation, were compared through
      an osteoarthritis model. METHODS AND MATERIALS: Osteoarthritis was induced in
      white New Zealand rabbits by anterior cruciate ligament section. After the
      induction period, the animals were allocated to receive HA-1 or HA-2 intra
      articularly in one knee whereas the contralateral knee was used as Operated
      Control. An additional group of non-operated animals was used as Healthy
      Controls. Samples of cartilage were taken for different measures: apoptosis,
      nitric oxide (nitrites) and hyaluronic acid in synovial fluid. RESULTS: The
      administration of HA-1 had a significant inhibitor effect on apoptosis of the
      chondrocytes compared to operated untreated animals (p = 0.0089), whereas this
      difference was not observed in the HA-2 knees. Levels of nitrites determined by
      HPLC in the HA-1 knees were similar to those in the Healthy group (p = 0.6551)
      whereas they were significantly higher in Operated Control and HA-2 groups (p =
      0.0001). The comparison between HA-1 and HA-2 also revealed significantly lower
      levels of nitrites in the HA-1 knees (p = 0.0001). Values of hyaluronic acid in
      synovial fluid did not show statistical differences between the different study
      groups. CONCLUSIONS: HA-1 and HA-2 showed different physico-chemical
      characteristics and these differences have resulted in different in vivo
      behaviour. As a consequence, not all the HA with similar molecular weight can be
      considered as equivalent.

PMID- 20148097
TI  - The effect of bangerter occlusion foils on blepharospasm and hemifacial spasm in
      occlusion-positive and occlusion-negative patients.
AB  - OBJECTIVE: To test the hypothesis that occlusion-positive (OP) patients with
      blepharospasm (BEB) or hemifacial spasm (HFS) will benefit from a Bangerter
      occlusion foil (BOF), compared to occlusion-negative (ON) patients. OP/ON was
      based on immediate improvement in spasm with placement of a hand in front of
      either eye. DESIGN: Prospective non-randomised single-centre pilot study.
      PARTICIPANTS: Fifteen-patients (6 BEB, 9 HFS). METHODS: Patients were identified
      as OP or ON and wore highest-density BOF tolerable over one spectacle lens for 1
      month. Outcomes were assessed at 1 month. MAIN OUTCOME MEASURES: Validated
      quality-of-life questionnaire (CDQ-24), scores of blink-rate and spasm severity
      assessed by two observers from video-recordings. RESULTS: OP group had mean
      improvement in all scores. There was no change or worsening of scores in the ON
      group. In both BEB and HFS, more OP patients reported subjective benefit from
      wearing a foil (2 of 4 BEB, and 2 of 2 HFS) compared to the ON group (0 of 2 BEB,
      and 1 of 7 HFS). CONCLUSION: OP patients with BEB and HFS are more likely to
      experience improvement in spasms from wearing a BOF compared to ON patients. The
      occlusion test should be considered on all patients with BEB or HFS.

PMID- 20148098
TI  - The effect of passive opium smoking on cardiovascular indices of rabbits with
      normal and ischemic hearts.
AB  - Some Asian people believe that opium can protect the cardiovascular system. To
      assess this belief, we investigated the effect of passive opium smoking (POS) on
      cardiovascular indices in rabbits with ischemic and non-ischemic hearts.Rabbits
      (n = 43) were divided into control (CTL), short term opium (SO) and long term
      opium (LO) groups. SO and LO groups were exposed to opium smoking for 3 days and
      4 weeks, respectively. ECG, blood pressure (BP), left ventricular pressure and
      cardiac troponin I levels were recorded. Isoproterenol (ISO) was injected to
      induce cardiac ischemia and after 4 h the above variables were measured along
      with cardiac histopathology assessment.All groups showed significant increments
      in troponin I level (P < 0.05) except the CTL group. This trend was more obvious
      in ISO-treated groups. Mean arterial pressure (MAP) significantly decreased in
      all groups (p< 0.05) except the LO group. Opium exposure attenuated ISO-induced
      myodegeneration but augmented tissue congestion and hemorrhage.In conclusion,
      higher troponin I serum level and ECG changes were found in passive opium smoking
      groups. This evidence is against the belief that opium can protect the
      cardiovascular system.

PMID- 20148099
TI  - Increased sinusoidal flow is not the primary stimulus to liver regeneration.
AB  - BACKGROUND: Hemodynamic changes in the liver remnant following partial
      hepatectomy (PHx) have been suggested to be a primary stimulus in triggering
      liver regeneration. We hypothesized that it is the increased sinusoidal flow per
      se and hence the shear-stress stimulus on the endothelial surface within the
      liver remnant which is the main stimulus to regeneration. In order to test this
      hypothesis we wanted to increase the sinusoidal flow without performing a
      concomitant liver resection. Accordingly, we constructed an aorto-portal shunt to
      the left portal vein branch creating a standardized four-fold increase in flow to
      segments II, III and IV. The impact of this manipulation was studied in both an
      acute model (6 animals, 9 hours) using a global porcine cDNA microarray chip and
      in a chronic model observing weight and histological changes (7 animals, 3
      weeks). RESULTS: Gene expression profiling from the shunted segments does not
      suggest that increased sinusoidal flow per se results in activation of genes
      promoting mitosis. Hyperperfusion over three weeks results in the whole liver
      gaining a supranormal weight of 3.9% of the total body weight (versus the normal
      2.5%). Contrary to our hypothesis, the weight gain was observed on the non
      shunted side without an increase in sinusoidal flow. CONCLUSIONS: An isolated
      increase in sinusoidal flow does not have the same genetic, microscopic or
      macroscopic impact on the liver as that seen in the liver remnant after partial
      hepatectomy, indicating that increased sinusoidal flow may not be a sufficient
      stimulus in itself for the initiation of liver regeneration.

PMID- 20148101
TI  - The influence of a hot environment on parental cooperation of a ground-nesting
      shorebird, the Kentish plover Charadrius alexandrinus.
AB  - BACKGROUND: Parental care often increases offspring survival, but is costly to
      the parents. A trade-off between the cost and benefit of care is expected, so
      that when care provisioning by both parents is essential for the success of
      young, for instance in extremely cold or hot environments, the parents should
      rear their young together. We investigated the latter hypothesis in a ground
      nesting shorebird, the Kentish plover Charadrius alexandrinus in an extremely hot
      environment, the Arabian Desert. Midday ground temperature was often above 50
      degrees C in our study site in Abu Dhabi (United Arab Emirates), thus leaving the
      eggs unattended even for a few minute risks overheating and death of embryos.
      RESULTS: Through the use of video surveillance systems we recorded incubation
      routines of male and female Kentish plovers at 28 nests over a full day (24 h).
      We show that ambient temperature had a significant influence on incubation
      behaviour of both sexes, and the relationships are often non-linear. Coordinated
      incubation between parents was particularly strong in midday with incubation
      shared approximately equally between the male and the female. The enhanced
      biparental incubation was due to males increasing their nest attendance with
      ambient temperature. CONCLUSIONS: Our results suggest biparental care is
      essential during incubation in the Kentish plover in extremely hot environments.
      Shared incubation may also help the parents to cope with heat stress themselves:
      they can relieve each other frequently from incubation duties. We suggest that
      once the eggs have hatched the risks associated with hot temperature are reduced:
      the chicks become mobile, and they gradually develop thermoregulation. When
      biparental care of young is no longer essential one parent may desert the family.
      The relaxed demand of the offspring may contribute to the diverse breeding
      systems exhibited by many shorebirds.

PMID- 20148100
TI  - Automatic measurement of epithelium differentiation and classification of
      cervical intraneoplasia by computerized image analysis.
AB  - BACKGROUND: The feasibility of evaluating an objective grading of cervical
      intraneoplasia lesions (CIN) is attempted using an automatic computerized system
      able to measure several valuable parameters with special reference to epithelium
      differentiation. METHODS: 4 groups of 10 images each were selected at random from
      68 consensus images coming from 80 archival cervical biopsies, normal (n = 10),
      CIN 1 (n = 10), CIN 2 (n = 10), CIN 3 (n = 10). Representative images of lesions
      were captured from the microscopic slides and were analyzed using mathematical
      morphology, with special reference toVoronoi tessellation and Delaunay
      triangulation. Epithelium surface, nuclear and cytoplasm area, triangle edge and
      area, total and upper nuclear index were precisely measured in each lesion, and
      discriminant coefficients were calculated therewith. A dilation/erosion
      coefficient was automatically defined using triangle edge length and nuclear
      radius in order to measure the epithelium ratio of differentiation. A histogram
      ratio was also automatically established between total nuclei and upper nuclei on
      top of differentiated epithelium. With the latter two ratios added to the nucleo
      cytoplasmic ratio, a cervical score able to classify CIN is proposed. RESULTS:
      There is a quasi-linear increase of mean cervical score values between normal
      epithelium and CIN 3: (27) for normal epithelium, (51) for CIN 1, (78) for CIN 2
      and (100) for CIN 3, with significant differences (P < 0.05). CONCLUSION: Our
      results highlight the possibility of applying a cervical score for the automatic
      grading of CIN lesions and thereby assisting the pathologist for improvement of
      grading. The automatic measure of epithelium differentiation ratio appears to be
      a new interesting parameter in computerized image analysis of cervical lesions.

PMID- 20148102
TI  - Dichlorvos exposure impedes extraction and amplification of DNA from insects in
      museum collections.
AB  - BACKGROUND: The insecticides dichlorvos, paradichlorobenzene and naphthalene have
      been commonly used to eradicate pest insects from natural history collections.
      However, it is not known how these chemicals affect the DNA of the specimens in
      the collections. We thus tested the effect of dichlorvos, paradichlorobenzene and
      naphthalene on DNA of insects (Musca domestica) by extracting and amplifying DNA
      from specimens exposed to insecticides in two different concentrations over
      increasing time intervals. RESULTS: The results clearly show that dichlorvos
      impedes both extraction and amplification of mitochondrial and nuclear DNA after
      relatively short time, whereas paradichlorobenzene and naphthalene do not.
      CONCLUSION: Collections treated with paradichlorobenzene and naphthalene, are
      better preserved concerning DNA, than those treated with dichlorvos. Non toxic
      pest control methods should, however, be preferred due to physical damage of
      specimens and putative health risks by chemicals.

PMID- 20148103
TI  - Key points in preventing tobacco use among adolescents.

PMID- 20148104
TI  - Acute effect of smoking on plasma Obestatin levels.
AB  - BACKGROUND: Smoking and smoking cessation are considered to be associated with
      weight changes. We have recently shown that smoking acutely increases plasma
      levels of ghrelin, a known orexigenic hormone. Obestatin is a peptide encoded by
      the ghrelin gene, which opposes ghrelin effects on food intake. We conducted a
      study in adult volunteers measuring plasma levels of obestatin immediately after
      initiation of smoking. METHODS: 31 volunteers (mean age 32.2 +/- 9.2 years and
      mean BMI 25.7 +/- 4.1), 17 smokers and 14 non-smokers, were enrolled in our
      study. The 2 groups were matched in age and BMI. Plasma obestatin concentrations
      were determined at baseline (T0), 2 (T2), 5 (T5), 15 (T15), and 60 (T60) minutes
      after the initiation of smoking. RESULTS: In all 31 subjects, no significant
      difference in the mean values of plasma obestatin levels was observed from
      baseline at T2, T5, T15 and T60 after initiation of smoking (overall p = 0.15).
      However, a trend for higher obestatin levels was noted in smokers vs non-smokers
      (overall p = 0.069), which was not related to the pack-years. CONCLUSION: On the
      contrary with ghrelin's response after smoking initiation, there is no such an
      acute response of plasma obestatin levels.

PMID- 20148105
TI  - Tobacco use prevalence, knowledge, and attitudes among newly diagnosed
      tuberculosis patients in Penang State and Wilayah Persekutuan Kuala Lumpur,
      Malaysia.
AB  - BACKGROUND: There is sufficient evidence to conclude that tobacco smoking is
      strongly linked to tuberculosis (TB) and a large proportion of TB patients may be
      active smokers. In addition, a previous analysis has suggested that a
      considerable proportion of the global burden of TB may be attributable to
      smoking. However, there is paucity of information on the prevalence of tobacco
      smoking among TB patients in Malaysia. Moreover, the tobacco-related knowledge,
      attitudes, and behaviors of TB patients who are smokers have not been previously
      explored. This study aimed to document the prevalence of smoking among newly
      diagnosed TB patients and to learn about the tobacco use knowledge and attitudes
      of those who are smokers among this population. METHODS: Data were generated on
      prevalence rates of smoking among newly diagnosed TB patients in the State of
      Penang from January 2008 to December 2008. The data were obtained based on a
      review of routinely collated data from the quarterly report on TB case
      registration. The study setting comprised of five healthcare facilities (TB
      clinics) located within Penang and Wilayah Persekutuan, Kuala Lumpur health
      districts in Malaysia, which were involved in a larger project, known as SCIDOTS
      Project. A 58-item questionnaire was used to assess the tobacco use knowledge,
      attitudes and behaviors of those TB patients who were smokers. RESULTS: Smoking
      status was determinant in 817 of 943 new cases of TB from January to December
      2008. Of this, it was estimated that the prevalence rates of current- and ex
      smoking among the TB patients were 40.27% (329/817) and 13.95% (114/817),
      respectively. The prevalence of ever-smoking among patients with TB was estimated
      to be 54,220 per 100,000 population. Of 120 eligible participants for the SCIDOTS
      Project, 88 responded to the survey (73.3% response rate) and 80 surveys were
      analyzed (66.7% usable rate). The mean (+/- SD) total score of tobacco use
      knowledge items was 4.23 +/- 2.66 (maximum possible score=11). More than half of
      the participants (51.3%) were moderately dependent to nicotine. A moderately
      large proportion of the respondents (41.2%) reported that they have ever
      attempted to quit smoking, while more than half (56.3%) have not. Less than half
      (47.5%) of the study participants had knowledge about the body system on which
      cigarette smoking has the greatest negative effect. The majority wrongly believed
      that smokeless tobacco can increase athletic performance (60%) and that it is a
      safe and harmless product (46.2%). An overwhelming proportion (>80%) of the
      patients believed that: smoking is a waste of money, tobacco use is very
      dangerous to health, and that smokers are more likely to die from heart disease
      when compared with non-smokers. The use of smokeless tobacco was moderately
      prevalent among the participants with 28.8% reporting ever snuffed, but the use
      of cigar and pipe was uncommon. CONCLUSION: Smoking prevalence rate is high among
      patients with TB in Malaysia. These patients generally had deficiencies in
      knowledge of tobacco use and its health dangers, but had positive attitudes
      against tobacco use. Efforts should be geared towards reducing tobacco use among
      this population due to its negative impact on TB treatment outcomes.

PMID- 20148106
TI  - Diachronic trends of employment outcome of prevocational training in psychiatric
      rehabilitation.
AB  - BACKGROUND: Although many rehabilitation programmes of prevocational training for
      chronic mentally ill persons living in the community have been funded, there is
      scarce literature about the diachronic trends of their long-term employment
      outcome. Thus the aim of the present study was to compare the 2-year employment
      outcome of three groups of chronic psychiatric outpatients, having attended
      similar prevocational rehabilitation programmes in different periods of time.
      METHODS: The first group (1984 to 1986) comprised 67 rehabilitees, the second
      (1988 to 1989) 53 rehabilitees and the third (2000 to 2001) 56 rehabilitees. The
      three groups were compared with regard to employment follow-up achievements and
      hospitalisation rates assessed at the end of the 2-year follow-up period by a
      constructed overall index, encompassing employment qualitative and quantitative
      characteristics. RESULTS: The third group compared to the first and second ones
      presented a worse employment outcome. No differences were found among the three
      groups with regard to hospitalisation rates. CONCLUSIONS: There has been a
      decline in the employment outcome of prevocational training during the current
      decade. This decline can be attributed to contextual adverse factors such as
      unemployment, a more demanding labour market and disability allowances offered by
      the state (the 'benefit trap'). Moreover, the training itself may be 'old
      fashioned' enough, thus providing the trainees with inadequate skills to obtain
      and maintain a competitive job.

PMID- 20148107
TI  - Characteristics of mentally ill offenders from 100 psychiatric court reports.
AB  - BACKGROUND: There is an increasing probability that the psychiatrist will,
      willingly or not, come into contact with mentally ill offenders in the course of
      their practice. There are increasing rates of violence, substance abuse and other
      psychiatric disorders that are of legal importance. Therefore, the aim of this
      work was to investigate the rates of different mental disorders in 100 court
      reports and to investigate the characteristics of mentally ill offenders.
      METHODS: All cases referred from different departments of the legal system to the
      forensic committee for assessment of legal accountability over 13-months duration
      were included. A specially designed form was prepared for data collection. Cases
      were classified into five groups: murder, robbery, financial offences, violent
      and simple offences and a group for other offences. Data were subjected to
      statistical analysis and comparisons between different groups of subjects were
      performed by analysis of variance (ANOVA). RESULTS: Men constituted 93% of cases.
      In all, 73% of offenders were younger than 40 years old. Schizophrenia cases made
      up 13% of the total, substance related cases constituted 56% and amphetamine
      cases alone made up 21%; 10% of cases were antisocial personality disorders, and
      51% of cases were classified as having a low education level. Unemployment was
      found in 34% of cases. The final decision of the forensic committee was full
      responsibility in 46% of cases and partial responsibility in 11% of cases, with
      33% considered non-responsible. A total of 58% of cases had had contact with
      psychiatric healthcare prior to the offence and in 9% of cases contact had been
      in the previous 12 weeks. A history of similar offences was found in 32% of
      cases. In all, 14% of the offences were murders, 8% were sexual crimes, and 31%
      were violent/simple crimes. CONCLUSIONS: The ability of the legal system to
      detect cases was good, while the ability of the healthcare system to predict
      crimes and offences was weak, as 58% of cases had had previous contact with the
      healthcare system previously. Substance abuse, especially amphetamine abuse,
      played an important role.

PMID- 20148108
TI  - Extrapyramidal side effects and suicidal ideation under fluoxetine treatment: a
      case report.
AB  - BACKGROUND: We present the case of a 52-year-old woman with depression who
      developed extrapyramidal symptoms (mainly parkinsonism) and suicidal ideation
      while on fluoxetine. METHODS: The patient underwent neurological and neuroimaging
      examination. RESULTS: The patient's neurological and neuroimaging examinations
      were normal and there was no other cause of extrapyramidal symptoms. The patient
      showed remission of the aforementioned symptomatology when fluoxetine was
      discontinued. CONCLUSIONS: This case shows that fluoxetine can be associated with
      extrapyramidal symptoms, and this may have an aggravating affect on clinical
      depression progress and the emergence of suicidal ideation.

PMID- 20148109
TI  - Sigma-1 receptor agonist fluvoxamine for delirium in patients with Alzheimer's
      disease.
AB  - BACKGROUND: Delirium in older adults is a common and serious acute
      neuropsychiatric syndrome, with core features of inattention and global cognitive
      impairment. Although antipsychotic drugs are the medications most frequently used
      to treat this syndrome, these drugs are associated with a variety of adverse
      events, including sedation, extrapyramidal side effects, and cardiac arrhythmias.
      METHODS: We report on two cases in which monotherapy of the selective serotonin
      reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in
      ameliorating the delirium of patients with Alzheimer's disease. RESULTS: Delirium
      Rating Scale (DRS) scores in the two patients with Alzheimer's disease decreased
      after fluvoxamine monotherapy. CONCLUSION: Doctors should consider that
      fluvoxamine could be an alternative approach in treating delirium in patients
      with Alzheimer's disease because of the risk of extrapyramidal side effects by
      antipsychotic drugs.

PMID- 20148110
TI  - A high protein moderate carbohydrate diet fed at discrete meals reduces early
      progression of N-methyl-N-nitrosourea-induced breast tumorigenesis in rats.
AB  - Breast cancer is the most prevalent cancer in American women. Dietary factors are
      thought to have a strong influence on breast cancer incidence. This study
      utilized a meal-feeding protocol with female Sprague-Dawley rats to evaluate
      effects of two ratios of carbohydrate:protein on promotion and early progression
      of breast tissue carcinomas. Mammary tumors were induced by N-methyl-N
      nitrosourea (MNU) at 52 d of age. Post-induction, animals were assigned to
      consume either a low protein high carbohydrate diet (LPHC; 15% and 60% of energy,
      respectively) or a high protein moderate carbohydrate diet (HPMC; 35% and 40% of
      energy, respectively) for 10 wk. Animals were fed 3 meals/day to mimic human
      absorption and metabolism patterns. The rate of palpable tumor incidence was
      reduced in HPMC relative to LPHC (12.9 +/- 1.4%/wk vs. 18.2 +/- 1.3%/wk). At 3
      wk, post-prandial serum insulin was larger in the LPHC relative to HPMC (+136.4
      +/- 33.1 pmol/L vs. +38.1 +/- 23.4 pmol/L), while at 10 wk there was a trend for
      post-prandial IGF-I to be increased in HPMC (P = 0.055). There were no
      differences in tumor latency, tumor surface area, or cumulative tumor mass
      between diet groups. The present study provides evidence that reducing the
      dietary carbohydrate:protein ratio attenuates the development of mammary tumors.
      These findings are consistent with reduced post-prandial insulin release
      potentially diminishing the proliferative environment required for breast cancer
      tumors to progress.

PMID- 20148111
TI  - Differential effect of maternal diet supplementation with alpha-Linolenic adcid
      or n-3 long-chain polyunsaturated fatty acids on glial cell
      phosphatidylethanolamine and phosphatidylserine fatty acid profile in neonate rat
      brains.
AB  - BACKGROUND: Dietary long-chain polyunsaturated fatty acids (LC-PUFA) are of
      crucial importance for the development of neural tissues. The aim of this study
      was to evaluate the impact of a dietary supplementation in n-3 fatty acids in
      female rats during gestation and lactation on fatty acid pattern in brain glial
      cells phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the neonates.
      METHODS: Sprague-Dawley rats were fed during the whole gestation and lactation
      period with a diet containing either docosahexaenoic acid (DHA, 0.55%) and
      eicosapentaenoic acid (EPA, 0.75% of total fatty acids) or alpha-linolenic acid
      (ALA, 2.90%). At two weeks of age, gastric content and brain glial cell PE and PS
      of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA)
      profile. Data were analyzed by bivariate and multivariate statistics. RESULTS: In
      the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric
      content (+65%, P < 0.0001) and brain glial cell PE (+18%, P = 0.0001) and PS
      (+15%, P = 0.0009) were significantly increased compared to the ALA group. The
      filtered correlation analysis (P < 0.05) underlined that levels of dihomo-gamma
      linolenic acid (DGLA), DHA and n-3 docosapentaenoic acid (DPA) were negatively
      correlated with arachidonic acid (ARA) and n-6 DPA in PE of brain glial cells. No
      significant correlation between n-3 and n-6 LC-PUFA were found in the PS dataset.
      DMA level in PE was negatively correlated with n-6 DPA. DMA were found to occur
      in brain glial cell PS fraction; in this class DMA level was correlated
      negatively with DHA and positively with ARA. CONCLUSION: The present study
      confirms that early supplementation of maternal diet with n-3 fatty acids
      supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE
      and PS in the neonate than ALA. Negative correlation between n-6 DPA, a
      conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that
      potentially be considered as a marker of tissue ethanolamine plasmalogen status.
      The combination of multivariate and bivariate statistics allowed to underline
      that the accretion pattern of n-3 LC-PUFA in PE and PS differ.

PMID- 20148112
TI  - Inverse relation between FASN expression in human adipose tissue and the insulin
      resistance level.
AB  - BACKGROUND: Adipose tissue is a key regulator of energy balance playing an active
      role in lipid storage and may be a dynamic buffer to control fatty acid flux.
      Just like PPARgamma, fatty acid synthesis enzymes such as FASN have been
      implicated in almost all aspects of human metabolic alterations such as obesity,
      insulin resistance or dyslipemia. The aim of this work is to investigate how FASN
      and PPARgamma expression in human adipose tissue is related to carbohydrate
      metabolism dysfunction and obesity. METHODS: The study included eighty-seven
      patients which were classified according to their BMI and to their glycaemia
      levels in order to study FASN and PPARgamma gene expression levels,
      anthropometric and biochemical variables. RESULTS: The main result of this work
      is the close relation between FASN expression level and the factors that lead to
      hyperglycemic state (increased values of glucose levels, HOMA-IR, HbA1c, BMI and
      triglycerides). The correlation of the enzyme with these parameters is inversely
      proportional. On the other hand, PPARgamma is not related to carbohydrate
      metabolism. CONCLUSIONS: We can demonstrate that FASN expression is a good
      candidate to study the pathophysiology of type II diabetes and obesity in humans.

PMID- 20148113
TI  - Sustained self-regulation of energy intake. Loss of weight in overweight
      subjects. Maintenance of weight in normal-weight subjects.
AB  - BACKGROUND: Dietary restraint is largely unsuccessful for controlling obesity. As
      an alternative, subjects can easily be trained to reliably recognize sensations
      of initial hunger (IH) a set of physiological sensations which emerge
      spontaneously, not necessarily at planned mealtimes, and may be the afferent arm
      of a homeostatic system of food intake regulation. Previously we have reported
      that IH is associated with blood glucose concentration (BG) below 81.8 mg/dL
      (4.55 mmol/l), (low blood glucose, LBG), and that a pattern of meals in which IH
      is present pre-meal (IHMP) improved insulin sensitivity, HbA1c and other
      cardiovascular risk factors. Here we report the effect upon weight in overweight
      and normal weight subjects. OBJECTIVE: To investigate whether the IHMP is
      associated with sustained loss of weight in overweight subjects over a 5 month
      period. METHODS: SEVENTY FOUR OVERWEIGHT SUBJECTS (OW: BMI > 25) and 107 normal
      weight (NW) subjects were randomly allocated to either trained (OW: N = 51; NW N
      = 79) or control (OW: N = 23; NW: N = 28) groups. All subjects were allocated
      post-randomization into either low or high mean pre-meal BG groups (LBG and HBG
      groups) using a demarcation point of 81.8 mg/dL. RESULTS: A SIGNIFICANT
      LONGITUDINAL DECREASE WAS FOUND IN BODY WEIGHT (TRAINED NW: -2.5 +/- 4.6 kg; OW 
      6.7 +/- 4.5 kg; controls: NW +3.5 +/- 4.0 kg and OW -3.4 +/- 4.0 kg; P = 0.006
      and 0.029) and in energy intake, mean BG, standard deviation of diary BG (BG as
      recorded by subjects' 7-day diary), BMI, and arm and leg skin-fold thickness in
      (OW and NW) HBG subjects. OW LBG subjects significantly decreased body weight
      (trained: -4.0 +/- 2.4 kg; controls: -0.4 +/- 3.7 kg; P = 0.037). 26 NW LBG
      subjects showed no longitudinal difference after training as did 9 control
      subjects. CONCLUSION: Over a 5 month period the IHMP resulted in significant loss
      of weight in OW subjects compared to controls practicing dietary restraint. NW
      subjects maintained weight overall, however NW HBG subjects also lost weight
      compared to controls.

PMID- 20148116
TI  - Torsion of a giant pedunculated liver hemangioma mimicking acute appendicitis: a
      case report.
AB  - Hemangiomas are the most common benign neoplasms affecting the liver. They occur
      at all ages. Most cases are asymptomatic and do not require any treatment.
      Rarely, hemangiomas can be pedunculated. If they undergo torsion and infarction,
      they become symptomatic. Herein; we report the case of a 31 year old male
      presenting with features of acute appendicitis: continuous right iliac fossa
      pain, rebound, guarding tenderness at McBurney' s point, nausea, anorexia,
      shifted white blood cell count and a Mantrels score of 6. At laparotomy a normal
      appendix was observed and a torsioned pedinculated liver hemangioma turned out to
      be the cause.

PMID- 20148114
TI  - Mutations in the nuclear localization sequence of the Aristaless related
      homeobox; sequestration of mutant ARX with IPO13 disrupts normal subcellular
      distribution of the transcription factor and retards cell division.
AB  - BACKGROUND: Aristaless related homeobox (ARX) is a paired-type homeobox gene. ARX
      function is frequently affected by naturally occurring mutations. Nonsense
      mutations, polyalanine tract expansions and missense mutations in ARX cause a
      range of intellectual disability and epilepsy phenotypes with or without
      additional features including hand dystonia, lissencephaly, autism or dysarthria.
      Severe malformation phenotypes, such as X-linked lissencephaly with ambiguous
      genitalia (XLAG), are frequently observed in individuals with protein truncating
      or missense mutations clustered in the highly conserved paired-type homeodomain.
      RESULTS: We have identified two novel point mutations in the R379 residue of the
      ARX homeodomain; c.1135C>A, p.R379S in a patient with infantile spasms and
      intellectual disability and c.1136G>T, p.R379L in a patient with XLAG. We
      investigated these and other missense mutations (R332P, R332H, R332C, T333N:
      associated with XLAG and Proud syndrome) predicted to affect the nuclear
      localisation sequences (NLS) flanking either end of the ARX homeodomain. The NLS
      regions are required for correct nuclear import facilitated by Importin 13
      (IPO13). We demonstrate that missense mutations in either the N- or C-terminal
      NLS regions of the homeodomain cause significant disruption to nuclear
      localisation of the ARX protein in vitro. Surprisingly, none of these mutations
      abolished the binding of ARX to IPO13. This was confirmed by co
      immunoprecipitation and immmuno fluorescence studies. Instead, tagged and
      endogenous IPO13 remained bound to the mutant ARX proteins, even in the RanGTP
      rich nuclear environment. We also identify the microtubule protein TUBA1A as a
      novel interacting protein for ARX and show cells expressing mutant ARX protein
      accumulate in mitosis, indicating normal cell division may be disrupted.
      CONCLUSIONS: We show that the most likely, common pathogenic mechanism of the
      missense mutations in NLS regions of the ARX homeodomain is inadequate
      accumulation and distribution of the ARX transcription factor within the nucleus
      due to sequestration of ARX with IPO13.

PMID- 20148115
TI  - The sigmoid volvulus: surgical timing and mortality for different clinical types.
AB  - BACKGROUND: In western countries intestinal obstruction caused by sigmoid
      volvulus is rare and its mortality remains significant in patients with late
      diagnosis. The aim of this work is to assess what is the correct surgical timing
      and how the prognosis changes for the different clinical types. METHODS: We
      realized a retrospective clinical study including all the patients treated for
      sigmoid volvulus in the Department of General Surgery, St Maria Hospital, Terni,
      from January 1996 till January 2009. We selected 23 patients and divided them in
      2 groups on the basis of the clinical onset: patients with clear clinical signs
      of obstruction and patients with subocclusive symptoms. We focused on 30-day
      postoperative mortality in relation to the surgical timing and procedure
      performed for each group. RESULTS: In the obstruction group mortality rate was
      44% and it concerned only the patients who had clinical signs and symptoms of
      peritonitis and that were treated with a sigmoid resection (57%). Conversely none
      of the patients treated with intestinal derotation and colopexy died. In the
      subocclusive group mortality was 35% and it increased up to 50% in those patients
      with a late diagnosis who underwent a sigmoid resection. CONCLUSIONS: The
      mortality of patients affected by sigmoid volvulus is related to the disease
      stage, prompt surgical timing, functional status of the patient and his
      collaboration with the clinicians in the pre-operative decision making process.
      Mortality is higher in both obstructed patients with generalized peritonitis and
      patients affected by subocclusion with late diagnosis and surgical treatment; in
      both scenarios a Hartmann's procedure is the proper operation to be considered.

PMID- 20148117
TI  - High frequency, cell type-specific visualization of fluorescent-tagged genomic
      sites in interphase and mitotic cells of living Arabidopsis plants.
AB  - BACKGROUND: Interphase chromosome organization and dynamics can be studied in
      living cells using fluorescent tagging techniques that exploit bacterial
      operator/repressor systems and auto-fluorescent proteins. A nuclear-localized
      Repressor Protein-Fluorescent Protein (RP-FP) fusion protein binds to operator
      repeats integrated as transgene arrays at defined locations in the genome. Under
      a fluorescence microscope, the tagged sites appear as bright fluorescent dots in
      living cells. This technique has been used successfully in plants, but is often
      hampered by low expression of genes encoding RP-FP fusion proteins, perhaps owing
      to one or more gene silencing mechanisms that are prevalent in plant cells.
      RESULTS: We used two approaches to overcome this problem. First, we tested
      mutations in four factors involved in different types of gene silencing and/or
      epigenetic modifications for their effects on nuclear fluorescence. Only
      mutations in DDM1, a chromatin remodelling ATPase involved in repeat-induced
      heterochromatin formation and DNA methylation, released silencing of the RP-FP
      fusion protein. This result suggested that the operator repeats can trigger
      silencing of the adjacent gene encoding the RP-FP fusion protein. In the second
      approach, we transformed the tagged lines with a second T-DNA encoding the RP-FP
      fusion protein but lacking operator repeats. This strategy avoided operator
      repeat-induced gene silencing and increased the number of interphase nuclei
      displaying fluorescent dots. In a further extension of the technique, we show
      that green fluorescent-tagged sites can be visualized on moving mitotic
      chromosomes stained with red fluorescent-labelled histone H2B. CONCLUSIONS: The
      results illustrate the propensity of operator repeat arrays to form
      heterochromatin that can silence the neighbouring gene encoding the RP-FP fusion
      protein. Supplying the RP-FP fusion protein in trans from a second T-DNA largely
      alleviates this problem. Depending on the promoter used to drive expression of
      the RP-FP fusion protein gene, the fluorescent tagged sites can be visualized at
      high frequency in different cell types. The ability to observe fluorescent dots
      on both interphase and mitotic chromosomes allows tagged sites to be tracked
      throughout the cell cycle. These improvements enhance the versatility of the
      fluorescent tagging technique for future studies of chromosome arrangement and
      dynamics in living plants.

PMID- 20148119
TI  - Go Sun Smart.
AB  - This is the story of Go Sun Smart, a worksite wellness program endorsed by the
      North American Ski Area Association and funded by the National Cancer Institute.
      Between 2000 and 2002 we designed and implemented a large-scale worksite
      intervention at over 300 ski resorts in North America with the objective of
      reducing ski area employees and guests risk for skin cancer by adopting sun safe
      practices. The following narrative describes the intervention in toto from its
      design and implementation through assessment. Our theory driven, experimentally
      tested intervention was successful in reducing employees' risks for skin cancer
      during and after the ski season. We also succeeded in making ski area guests more
      aware of the need to take sun safe precautions with both themselves and their
      children.

PMID- 20148118
TI  - Willingness to pay for rapid diagnostic tests for the diagnosis and treatment of
      malaria in southeast Nigeria: ex post and ex ante.
AB  - BACKGROUND: The introduction of rapid diagnostic tests (RDTs) has improved the
      diagnosis and treatment of malaria. However, any successful control of malaria
      will depend on socio-economic factors that influence its management in the
      community. Willingness to pay (WTP) is important because consumer responses to
      prices will influence utilization of services and revenues collected. Also the
      consumer's attitude can influence monetary valuation with respect to different
      conditions ex post and ex ante. METHODS: WTP for RDT for Malaria was assessed by
      the contingent valuation method using a bidding game approach in rural and urban
      communities in southeast Nigeria. The ex post WTP was assessed at the health
      centers on 618 patients immediately following diagnosis of malaria with RDT and
      the ex ante WTP was assessed by household interviews on 1020 householders with a
      prior history of malaria. RESULTS: For the ex ante WTP, 51% of the respondents in
      urban and 24.7% in rural areas were willing to pay for RDT. The mean WTP (235.49
      naira) in urban is higher than WTP (182.05 Naira) in rural areas. For the ex post
      WTP, 89 and 90.7% of the respondents in urban and rural areas respectively were
      WTP. The mean WTP (372.30 naira) in urban is also higher than (296.28 naira) in
      rural areas. For the ex post scenario, the lower two Social Economic Status (SES)
      quartiles were more willing to pay and the mean WTP is higher than the higher two
      SES while in the ex ante scenario, the higher two SES quartiles were more WTP and
      with a higher WTP than the lower two SES quartile. Ex ante and ex post WTP were
      directly dependent on costs. CONCLUSION: The ex post WTP is higher than the ex
      ante WTP and both are greater than the current cost of RDTs. Urban dwellers were
      more willing to pay than the rural dwellers. The mean WTP should be considered
      when designing suitable financial strategies for making RDTs available to
      communities.

PMID- 20148120
TI  - Sibling Contagion for Drinking in Adolescence: A Micro Process Framework.
AB  - Siblings represent an important social influence on alcohol use in adolescence.
      That said, there is a need for studies that examine potential mechanisms by which
      siblings exert an influence on the likelihood of drinking in adolescence. This
      paper illustrates a method that utilizes videotaped interaction between sibling
      dyads along with a micro social coding system that captures rule break behavior
      between siblings. Sibling interaction was observed in sibling pairs participating
      in the Iowa Youth and Families Project (IYFP) at baseline; younger sibling use of
      alcohol was tracked for 3 additional annual assessments. Exposure to older
      sibling rule break at baseline was associated with later use of alcohol by
      younger siblings across the 3 annual assessments. Micro social methods hold
      promise for uncovering processes that underlie sibling contagion for alcohol use
      in adolescence.

PMID- 20148121
TI  - Is work-family balance more than conflict and enrichment?
AB  - This study deepens our theoretical and practical understanding of work-family
      balance, defined as the 'accomplishment of role-related expectations that are
      negotiated and shared between an individual and his/her role-related partners in
      the work and family domains' (Grzywacz & Carlson, 2007: 458). We develop a new
      measure of work-family balance and establish discriminant validity between it,
      work-family conflict, and work-family enrichment. Further, we examine the
      relationship of work-family balance with six key work and family outcomes.
      Results suggest that balance explains variance beyond that explained by
      traditional measures of conflict and enrichment for five of six outcomes tested:
      job satisfaction, organizational commitment, family satisfaction, family
      performance, and family functioning. We conclude with a discussion of the
      applications of our work.

PMID- 20148122
TI  - Cognitive Imitation in Autism.

PMID- 20148123
TI  - Rational Choice and Developmental Influences on Recidivism Among Adolescent
      Felony Offenders.
AB  - Recent case law and social science both have claimed that the developmental
      limitations of adolescents affect their capacity for control and decision making
      with respect to crime, diminishing their culpability and reducing their exposure
      to punishment. Social science has focused on two concurrent adolescent
      developmental influences: the internalization of legal rules and norms that
      regulate social and antisocial behaviors, and the development of rationality to
      frame behavioral choices and decisions. The interaction of these two
      developmental processes, and the identification of one domain of socialization
      and development as the primary source of motivation or restraint in adolescence,
      is the focus of this article. Accordingly, we combine rational choice and legal
      socialization frameworks into an integrated, developmental model of criminality.
      We test this framework in a large sample of adolescent felony offenders who have
      been interviewed at six-month intervals for two years. Using hierarchical and
      growth curve models, we show that both legal socialization and rational choice
      factors influence patterns of criminal offending over time. When punishment risks
      and costs are salient, crime rates are lower over time. We show that procedural
      justice is a significant antecedent of legal socialization, but not of rational
      choice. We also show that both mental health and developmental maturity moderate
      the effects of perceived crime risks and costs on criminal offending.

PMID- 20148124
TI  - Proteomic Analysis of Vascular Endothelial Cells-Effects of Laminar Shear Stress
      and High Glucose.
AB  - This study directly measured the relative protein levels in bovine aortic
      endothelial cells (BAEC) that were cultured for two weeks in normal (5 mM, NG) or
      high (22 mM, HG) glucose and then were subjected to laminar shear stress at 0 or
      15 dynes/cm(2). Membrane preparations were labeled with one of the four isobaric
      tagging reagents (iTRAQ), followed by LC-MS/MS analysis. The results showed that
      HG and/or shear stress induced alterations in various membrane associated
      proteins involving many signaling pathways. While shear stress induced an
      increase in heat shock proteins and protein ubiquitination, which remained
      enhanced in HG, the effects of shear stress on the mechanosensing and protein
      phosphorylation pathways were altered by HG. These results were validated by
      Western blot analysis, suggesting that HG importantly modulates shear stress
      mediated endothelial function.

PMID- 20148125
TI  - Cognitive Testing and the Validity of Child-Report Data from the Elementary
      School Success Profile.
AB  - The Elementary School Success Profile (ESSP) is a social environmental assessment
      tool that collects data from 3(rd), 4(th), and 5(th) graders, their
      parents/guardians, and their teachers. Ensuring the validity of the data
      collected with the child report component was a primary concern during the
      development of the ESSP. This article describes how cognitive testing was used to
      promote the validity of ESSP child report data. Four types of response problems
      were identified in data collected from 58 children. Strategies to address
      problems are described, and evidence of the association between item
      modifications and improved performance is presented. Cognitive testing is
      recommended as a standard procedure in the development of child report
      instruments.

PMID- 20148126
TI  - The effect of statistical noise on IMRT plan quality and convergence for MC-based
      and MC-correction-based optimized treatment plans.
AB  - Monte Carlo (MC) is rarely used for IMRT plan optimization outside of research
      centres due to the extensive computational resources or long computation times
      required to complete the process. Time can be reduced by degrading the
      statistical precision of the MC dose calculation used within the optimization
      loop. However, this eventually introduces optimization convergence errors (OCEs).
      This study determines the statistical noise levels tolerated during MC-IMRT
      optimization under the condition that the optimized plan has OCEs <100 cGy (1.5%
      of the prescription dose) for MC-optimized IMRT treatment plans.Seven-field
      prostate IMRT treatment plans for 10 prostate patients are used in this study.
      Pre-optimization is performed for deliverable beams with a pencil-beam (PB) dose
      algorithm. Further deliverable-based optimization proceeds using: (1) MC-based
      optimization, where dose is recomputed with MC after each intensity update or (2)
      a once-corrected (OC) MC-hybrid optimization, where a MC dose computation defines
      beam-by-beam dose correction matrices that are used during a PB-based
      optimization. Optimizations are performed with nominal per beam MC statistical
      precisions of 2, 5, 8, 10, 15, and 20%. Following optimizer convergence, beams
      are re-computed with MC using 2% per beam nominal statistical precision and the 2
      PTV and 10 OAR dose indices used in the optimization objective function are
      tallied. For both the MC-optimization and OC-optimization methods, statistical
      equivalence tests found that OCEs are less than 1.5% of the prescription dose for
      plans optimized with nominal statistical uncertainties of up to 10% per beam. The
      achieved statistical uncertainty in the patient for the 10% per beam simulations
      from the combination of the 7 beams is ~3% with respect to maximum dose for
      voxels with D>0.5D(max). The MC dose computation time for the OC-optimization is
      only 6.2 minutes on a single 3 Ghz processor with results clinically equivalent
      to high precision MC computations.

PMID- 20148127
TI  - Frequency Dependence of Pulsed EPR Experiments.
AB  - The frequency dependence of the signal-to-noise ratio (S/N) that is theoretically
      possible for pulsed EPR experiments is the same as for continuous wave
      experiments. To select the optimum resonance frequency or frequencies for pulsed
      EPR experiments it is important to consider not only S/N, but also orientation
      selection, depth of spin echo modulation, and intensities of forbidden
      transitions. Evaluation of factors involved in selecting the optimum frequency
      for pulsed EPR measurements of distances between spins is discussed.

PMID- 20148128
TI  - The Malawi Diffusion and Ideational Change Project 2004-06: Data collection, data
      quality, and analysis of attrition.
AB  - In this paper we evaluate the quality of survey data collected by the Malawi
      Diffusion and Ideational Change Project by investigating four potential sources
      of bias: sample representativeness, interviewer effects, response unreliability,
      and sample attrition. We discuss the results of our analysis and implications of
      our findings for the collection of data in similar contexts.

PMID- 20148129
TI  - Hotspots and Coldspots: Household and village-level variation in orphanhood
      prevalence in rural Malawi.
AB  - We explore the characteristics of households and villages in which orphans are
      resident in two areas of Malawi. We first review pertinent themes in qualitative
      data collected in our research sites. Then, using spatial analysis, we show how
      positive and negative clusters of orphans - which we term orphanhood "hotspots"
      and "coldspots" - can be found at the village and sub-village levels. In the
      third and longest section of the paper, and using multilevel analyses with both
      simple and complex variance structures, we evaluate the relationship between the
      presence of orphans and a range of individual, household and village-level
      characteristics, including households' spatial relationship to each other and to
      other local sites of significance. This series of analyses shows that the most
      important covariates of orphan presence are household size, wealth, and religious
      characteristics, with all measured simultaneously at both household and village
      level. In addition, most of these have heterogenous effects across villages. We
      conclude by reviewing some difficulties in explaining causal mechanisms
      underlying these observed relationships, and discuss conceptual, theoretical and
      programmatic implications.

PMID- 20148130
TI  - Semiparametric latent covariate mixed-effects models with application to a colon
      carcinogenesis study.
AB  - We study a mixed-effects model in which the response and the main covariate are
      linked by position. While the covariate corresponding to the observed response is
      not directly observable, there exists a latent covariate process that represents
      the underlying positional features of the covariate. When the positional features
      and the underlying distributions are parametric, the expectation-maximization
      (EM) is the most commonly used procedure. Though without the parametric
      assumptions, the practical feasibility of a semi-parametric EM algorithm and the
      corresponding inference procedures remain to be investigated. In this paper, we
      propose a semiparametric approach, and identify the conditions under which the
      semiparametric estimators share the same asymptotic properties as the
      unachievable estimators using the true values of the latent covariate; that is,
      the oracle property is achieved. We propose a Monte Carlo graphical evaluation
      tool to assess the adequacy of the sample size for achieving the oracle property.
      The semiparametric approach is later applied to data from a colon carcinogenesis
      study on the effects of cell DNA damage on the expression level of oncogene bcl
      2. The graphical evaluation shows that, with moderate size of subunits, the
      numerical performance of the semiparametric estimator is very close to the
      asymptotic limit. It indicates that a complex EM-based implementation may at most
      achieve minimal improvement and is thus unnecessary.

PMID- 20148131
TI  - New Therapeutics Targeting Colon Cancer Stem Cells.
AB  - The recent identification of tumor-initiating colorectal cancer (CRC) stem cells
      in the pathogenesis of CRC has provided a potential target for novel
      therapeutics. Many details about CRC stem cells, however, remain poorly
      understood. Several potential markers of CRC stem cells have been proposed,
      including CD133, CD44, and, recently, Lgr5. Attention also has been drawn to
      control of stem cell self-renewal, proliferation, and differentiation by the Wnt
      and transforming growth factor (TGF)-beta pathways. Disruption of Wnt signaling,
      via loss of APC (adenomatous polyposis coli), is among the earliest events in the
      multistage progression of CRC and likely occurs in basal crypt stem cells,
      generating a neoplastic cell population that then expands upward to occupy the
      rest of the crypt. TGF-beta signaling is a key tumor suppressor pathway, and
      mutations in the type II receptor and Smad4 are observed in CRC specimens and are
      associated with more aggressive disease in tumors with disrupted Wnt signaling.
      Loss of the TGF-beta adaptor protein beta(2)-spectrin is associated with loss of
      colonic cell polarity and architecture, and its expression parallels that of
      Smad4. This review suggests rational approaches to target CRC stem cells as a
      novel and effective way to treat advanced and difficult-to-treat CRC.

PMID- 20148132
TI  - A nearly exhaustive search for CpG islands on whole chromosomes.
AB  - CpG islands are genome subsequences with an unexpectedly high number of CG di
      nucleotides. They are typically identified using filtering criteria (e.g., G+C%
      expected vs. observed CpG ratio and length) and are computed using sliding window
      methods. Most such studies illusively assume an exhaustive search of CpG islands
      are achieved on the genome sequence of interest. We devise a Lexis diagram and
      explicitly show that filtering criteria-based definitions of CpG islands are
      mathematically incomplete and non-operational. These facts imply that the sliding
      window methods frequently fail to identify a large percentage of subsequences
      that meet the filtering criteria. We also demonstrate that an exhaustive search
      is computationally expensive. We develop the Hierarchical Factor Segmentation
      (HFS) algorithm, a pattern recognition technique with an adaptive model selection
      device to overcome the incompleteness and non-operational drawbacks, and to
      achieve effective computations for identifying CpG-islands. The concept of a CpG
      island "core" is introduced and computed using the HFS algorithm, which is
      independent from any specific filtering criteria. Upon such a CpG island "core,"
      a CpG-island is constructed using a Lexis diagram. This two-step computational
      approach provides a nearly exhaustive search for CpG islands that can be
      practically implemented on whole chromosomes. In a simulation study realistically
      mimicking CpG-island dynamics through a Hidden Markov Model we demonstrate that
      this approach retains very high sensitivity and specificity, that is, very low
      rates of false positives and false negatives. Finally, we apply the HFS algorithm
      to identify CpG island cores on human chromosome 21.

PMID- 20148133
TI  - SIMULATION FROM ENDPOINT-CONDITIONED, CONTINUOUS-TIME MARKOV CHAINS ON A FINITE
      STATE SPACE, WITH APPLICATIONS TO MOLECULAR EVOLUTION.
AB  - Analyses of serially-sampled data often begin with the assumption that the
      observations represent discrete samples from a latent continuous-time stochastic
      process. The continuous-time Markov chain (CTMC) is one such generative model
      whose popularity extends to a variety of disciplines ranging from computational
      finance to human genetics and genomics. A common theme among these diverse
      applications is the need to simulate sample paths of a CTMC conditional on
      realized data that is discretely observed. Here we present a general solution to
      this sampling problem when the CTMC is defined on a discrete and finite state
      space. Specifically, we consider the generation of sample paths, including
      intermediate states and times of transition, from a CTMC whose beginning and
      ending states are known across a time interval of length T. We first unify the
      literature through a discussion of the three predominant approaches: (1) modified
      rejection sampling, (2) direct sampling, and (3) uniformization. We then give
      analytical results for the complexity and efficiency of each method in terms of
      the instantaneous transition rate matrix Q of the CTMC, its beginning and ending
      states, and the length of sampling time T. In doing so, we show that no method
      dominates the others across all model specifications, and we give explicit proof
      of which method prevails for any given Q, T, and endpoints. Finally, we introduce
      and compare three applications of CTMCs to demonstrate the pitfalls of choosing
      an inefficient sampler.

PMID- 20148134
TI  - Need of assistance with daily oral hygiene measures among nursing home resident
      elderly versus the actual assistance received from the staff.
AB  - The aim was to evaluate the need of assistance with daily oral hygiene measures
      among nursing home resident elderly versus the actual assistance received from
      the staff. The need of daily oral hygiene assistance was assessed descriptively
      for nursing home resident elderly who participated in an annual oral health
      screening in three geographical regions in Sweden, in the year 2008. All
      individuals of age >/= 65 years were included (n = 22,453; 6,327 men; 16,126
      women). The proportion of individuals in need of assistance with daily oral
      hygiene measures was 77.5 % (n=22,453), whereas the proportion of individuals
      receiving assistance with daily oral hygiene measures was 6.9 % in total
      (n=22,453). The proportions were largely similar in all geographical regions.
      There seems to be a large discrepancy between the need of assistance with daily
      oral hygiene measures, and the oral hygiene assistance received, among nursing
      home resident elderly.

PMID- 20148135
TI  - Influence of prosthetic screw material on joint stability in passive and non
      passive implant-supported dentures.
AB  - OBJECTIVES: This study evaluated the influence of prosthetic screw material on
      joint stability in implantsupported dentures at two levels of fit. METHODS: Ten
      mandibular implant-supported dentures were fabricated. Twenty cast models were
      fabricated using these dentures. Four groups (n=10) were tested, according to the
      vertical fit of the dentures [passive and non-passive] and prosthetic screw
      materials [titanium (Ti) or gold (Au) alloy]. The one-screw test was performed to
      quantify the vertical misfits using an optic microscope. The loosening torque for
      the prosthetic screws was measured 24 hours after the tightening torque (10 Ncm)
      using a digital torque meter. Data were analyzed by two-way ANOVA and Tukey's
      test (alpha=0.05). RESULTS: Overall, dentures with passive fit and Ti screws
      resulted in significantly higher loosening torque of the prosthetic screws
      (p<0.05). No significant interaction was found between fit level and screw
      material (p=0.199). The prosthetic screw material and fit of implant-supported
      dentures have an influence on screw joint stability. Ti screws presented higher
      joint stability than Au screws and minimum of misfit should be found clinically
      to improve the mechanical behavior of the screw joint.

PMID- 20148137
TI  - Total hip and knee replacement surgery results in changes in leukocyte and
      endothelial markers.
AB  - BACKGROUND: It is estimated that over 8 million people in the United Kingdom
      suffer from osteoarthritis. These patients may require orthopaedic surgical
      intervention to help alleviate their clinical condition. Investigations presented
      here was to test the hypothesis that total hip replacement (THR) and total knee
      replacement (TKR) orthopaedic surgery result in changes to leukocyte and
      endothelial markers thus increasing inflammatory reactions postoperatively.
      METHODS: During this 'pilot study', ten test subjects were all scheduled for THR
      or TKR elective surgery due to osteoarthritis. Leukocyte concentrations were
      measured using an automated full blood count analyser. Leukocyte CD11b (Mac-1)
      and CD62L cell surface expression, intracellular production of H(2)O(2 )and
      elastase were measured as markers of leukocyte function. Von Willebrand factor
      (vWF) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured as
      markers of endothelial activation. RESULTS: The results obtained during this
      study demonstrate that THR and TKR orthopaedic surgery result in similar changes
      of leukocyte and endothelial markers, suggestive of increased inflammatory
      reactions postoperatively. Specifically, THR and TKR surgery resulted in a
      leukocytosis, this being demonstrated by an increase in the total leukocyte
      concentration following surgery. Evidence of leukocyte activation was
      demonstrated by a decrease in CD62L expression and an increase in CD11b
      expression by neutrophils and monocytes respectively. An increase in the
      intracellular H(2)O(2 )production by neutrophils and monocytes and in the
      leukocyte elastase concentrations was also evident of leukocyte activation
      following orthopaedic surgery. With respect to endothelial activation, increases
      in vWF and sICAM-1 concentrations were demonstrated following surgery.
      CONCLUSION: In general it appeared that most of the leukocyte and endothelial
      markers measured during these studies peaked between days 1-3 postoperatively. It
      is proposed that by allowing orthopaedic surgeons access to alternative
      laboratory markers such as CD11b, H(2)O(2 )and elastase, CD62L, vWF and sICAM-1,
      an accurate assessment of the extent of inflammation due to surgery per se could
      be made. Ultimately, the leukocyte and endothelial markers assessed during this
      investigation may have a role in monitoring potential infectious complications
      that can occur during the postoperative period.

PMID- 20148136
TI  - Signaling pathways involved in LPS induced TNFalpha production in human
      adipocytes.
AB  - BACKGROUND: The development of obesity has been linked to an inflammatory
      process, and the role of adipose tissue in the secretion of pro-inflammatory
      molecules such as IL-6 or TNFalpha has now been largely confirmed. Although
      TNFalpha secretion by adipose cells is probably induced, most notably by TLR
      ligands, the activation and secretion pathways of this cytokine are not yet
      entirely understood. Moreover, given that macrophagic infiltration is a
      characteristic of obesity, it is difficult to clearly establish the level of
      involvement of the different cellular types present within the adipose tissue
      during inflammation. METHODS: Primary cultures of human adipocytes and human
      peripheral blood mononuclear cells were used. Cells were treated with a pathogen
      associated molecular pattern: LPS, with and without several kinase inhibitors.
      Western blot for p38 MAP Kinase was performed on cell lysates. TNFalpha mRNA was
      detected in cells by RT-PCR and TNFalpha protein was detected in supernatants by
      ELISA assays. RESULTS: WE SHOW FOR THE FIRST TIME THAT THE PRODUCTION OF TNFALPHA
      IN MATURE HUMAN ADIPOCYTES IS MAINLY DEPENDENT UPON TWO PATHWAYS: NFkappaB and
      p38 MAP Kinase. Moreover, we demonstrate that the PI3Kinase pathway is clearly
      involved in the first step of the LPS-pathway. Lastly, we show that adipocytes
      are able to secrete a large amount of TNFalpha compared to macrophages.
      CONCLUSION: This study clearly demonstrates that the LPS induced activation
      pathway is an integral part of the inflammatory process linked to obesity, and
      that adipocytes are responsible for most of the secreted TNFalpha in inflamed
      adipose tissue, through TLR4 activation.

PMID- 20148138
TI  - Gangrenous meckel's diverticulum in a strangulated umbilical hernia in a 42 year
      old woman: a case report.
AB  - INTRODUCTION: Meckel's diverticulum affects 1 - 3% of general population and is
      known as the most common anomaly of gastrointestinal tract. However, its
      estimated lifetime complication rate is approximately 4%. Intestinal obstruction
      is most common complication of Meckel's diverticulum in adult population. CASE
      PRESENTATION: In the present study, we reported a 42-year-old female patient with
      a gangrenous Meckel's diverticulum in a strangulated umbilical hernia sac treated
      by dissection of diverticulomesenteric bands and diverticulectomy. In 36 months
      follow-up, there was neither any complication nor recurrence of hernia.
      CONCLUSION: This case represents a gangrenous Meckel's diverticulum in a
      strangulated umbilical hernia sac diagnosed in case of emergency. Although it is
      a very rare phenomenon, we should be vigilant for this entity especially in case
      of emergency.

PMID- 20148139
TI  - A case of primary biliary cirrhosis associated with pernicious anemia: a case
      report.
AB  - Primary biliary cirrhosis is often associated with autoimmune diseases. However,
      its association with pernicious anemia has rarely been reported.We report a case
      of a 68-year-old woman who presented jaundice and pruritus. Mildly elevated serum
      levels of alkaline phosphatase and gamma-glutamyl transpeptidase were detected.
      The titer of anti-mitochondrial M(2 )anti-body was elevated. Histology of liver
      biopsy showed features of primary biliary cirrhosis. In addition, aregenerative
      macrocytic anemia was found in the full blood count. The diagnosis of pernicious
      anemia was established by megaloblastosis in bone marrow, atrophic gastritis
      without Helicobacter pylori, low level of vitamin B(12 )and good response to
      treatment regimen of vitamin B(12). The association of primary biliary cirrhosis
      and pernicious anemia is unlikely to be casual and may be explained by autoimmune
      mechanism commonly shared by the diseases.

PMID- 20148140
TI  - Giant splenic pseudocyst, a rare aetiology of abdominal tumor: a case report.
AB  - INTRODUCTION: Splenic pseudocysts are nonparasitic cyst without epithelial
      lining. We report this case especially by its way of revelation, its large size
      and its per operative presentation which needed total splenectomy. To this
      opportunity, we discuss the diagnostic procedure and therapeutic indications.
      CASE PRESENTATION: A twenty-year old Senegalese woman, was admitted with a three
      month history of spontaneous abdominal mass associated with a pain.
      Ultrasonography and CT scan found the giant splenic pseudocyst with a diameter of
      20 cm which needed a total splenectomy by median laparotomy. CONCLUSION: Usually,
      symptomless splenic cysts are untreated. When surgical treatment is indicated,
      recommendations are to preserve splenic parenchyma by partial splenectomy or
      fenestration especially by laparoscopy. Total splenectomy retains some guidance.

PMID- 20148141
TI  - An unusual Spigelian hernia involving the appendix: a case report.
AB  - INTRODUCTION: Spigelian herniae are uncommon and frequently pose a diagnostic
      challenge. CASE PRESENTATION: We report the case of a 71-year-old man in whom an
      ischaemic appendix was found within the sac of a Spigelian hernia during
      emergency repair. CONCLUSIONS: There are very few reported cases in which an
      appendix has been found within a Spigelian hernia, in the absence of inflammatory
      bowel disease. An awareness of the range of viscera which may be encountered in
      Spigelian herniae is important for safe repair.

PMID- 20148142
TI  - Submandibular displacement of a mandibular third molar root during extraction: a
      case report.
AB  - A 46-year-old female patient with complaints of pain and swelling on right
      submandibular region and limitation on mouth opening was reported. She had
      undergone an unsuccessful surgical procedure under local anesthesia performed by
      a general practitioner for removal of impacted mandibuler right third molar 1
      week earlier. On clinical examination floor of the mouth was tender to palpation.
      Panoramic and the periapical radiographs showed presence of a radiopaque mass
      similar to that of a tooth root. Computed tomography scans were obtained for
      detailed radiographic examination, thereby the presence of a high density area in
      the submandibular region was detected. Under general anesthesia the displaced
      root was removed and the postoperative course was uneventful.

PMID- 20148143
TI  - High rates of unsuccessful transfer to adult care among young adults with
      juvenile idiopathic arthritis.
AB  - BACKGROUND: This study aimed to describe the proportion of patients with juvenile
      idiopathic arthritis (JIA) who had experienced an unsuccessful transfer from a
      pediatric rheumatology team to an adult rheumatologist and to compare the
      characteristics of those who achieved successful transfer to those who did not.
      METHODS: We conducted a systematic chart review of all patients with JIA who
      attended their final Montreal Children's Hospital JIA clinic appointment between
      1992 and 2005. We tracked these patients for the two years after transfer to an
      adult rheumatologist. We then compared characteristics of patients with
      successful and unsuccessful transfers of care. Variables pertaining to disease
      characteristics, disease severity and psychosocial factors were examined.
      Univariate analyses were performed to determine if any single factor was
      associated with the outcome of unsuccessful transfer of care. RESULTS: 52% of
      patients fulfilled our criteria for unsuccessful transfer. Of the variables
      tested, an active joint count (AJC) of zero at last visit was associated with the
      outcome of unsuccessful transfer (OR = 2.67 (CI 1.16-6.16; p = 0.0199)).
      CONCLUSIONS: Despite the presence of a coordinated process of transfer from
      pediatric to adult health care for the majority of the patients in this study,
      there was a high rate of unsuccessful transfer and/or sustained follow up which
      is disheartening. We found that patients with less active disease at the time of
      transfer, as indicated by a lower AJC, were more likely to be lost to follow up.
      Recent literature suggests that even in the least severe categories of JIA, 50%
      of patients persist with active disease into adulthood. Thus educating all JIA
      patients about the possibility of disease flare in adulthood may improve their
      adherence to recommendations for sustained follow-up in the adult milieu. This
      may lead to improvement of longitudinal outcomes for all JIA patients.

PMID- 20148144
TI  - Transient oligoarthritis of the lower extremity following influenza B virus
      infection: Case report.
AB  - A 12-year-old girl developed influenza B virus infection proven by typical
      symptoms and detection of the virus in a nasopharyngeal swab by culture and PCR.
      Two weeks later she developed an otherwise unexplained transient oligoarthritis
      of small joints of the left foot. Influenza viruses may be a hitherto
      underappreciated cause of a post-infectious arthritis.

PMID- 20148145
TI  - Are psychiatrists an endangered species?

PMID- 20148146
TI  - The long-term costs of traumatic stress: intertwined physical and psychological
      consequences.
AB  - The gradual emergence of symptoms following exposure to traumatic events has
      presented a major conceptual challenge to psychiatry. The mechanism that causes
      the progressive escalation of symptoms with the passage of time leading to
      delayed onset post-traumatic stress disorder (PTSD) involves the process of
      sensitization and kindling. The development of traumatic memories at the time of
      stress exposure represents a major vulnerability through repeated environmental
      triggering of the increasing dysregulation of an individual's neurobiology. An
      increasing body of evidence demonstrates how the increased allostatic load
      associated with PTSD is associated with a significant body of physical morbidity
      in the form of chronic musculoskeletal pain, hypertension, hyperlipidaemia,
      obesity and cardiovascular disease. This increasing body of literature suggests
      that the effects of traumatic stress need to be considered as a major
      environmental challenge that places individual's physical and psychological
      health equally at risk. This broader perspective has important implications for
      developing treatments that address the underlying dysregulation of cortical
      arousal and neurohormonal abnormalities following exposure to traumatic stress.

PMID- 20148147
TI  - Mentalization based treatment for borderline personality disorder.
AB  - Mentalizing is the process by which we make sense of each other and ourselves,
      implicitly and explicitly, in terms of subjective states and mental processes. It
      is a profoundly social construct in the sense that we are attentive to the mental
      states of those we are with, physically or psychologically. Given the generality
      of this definition, most mental disorders will inevitably involve some
      difficulties with mentalization, but it is the application of the concept to the
      treatment of borderline personality disorder (BPD), a common psychiatric
      condition with important implications for public health, that has received the
      most attention. Patients with BPD show reduced capacities to mentalize, which
      leads to problems with emotional regulation and difficulties in managing
      impulsivity, especially in the context of interpersonal interactions.
      Mentalization based treatment (MBT) is a time-limited treatment which structures
      interventions that promote the further development of mentalizing. It has been
      tested in research trials and found to be an effective treatment for BPD when
      delivered by mental health professionals given limited additional training and
      with moderate levels of supervision. This supports the general utility of MBT in
      the treatment of BPD within generic mental health services.

PMID- 20148148
TI  - The detection and treatment of depression in the physically ill.
AB  - DEPRESSION AND CHRONIC PHYSICAL ILLNESS ARE IN RECIPROCAL RELATIONSHIP WITH ONE
      ANOTHER: not only do many chronic illnesses cause higher rates of depression, but
      depression has been shown to antedate some chronic physical illnesses. Depression
      associated with physical illness is less well detected than depression occurring
      on its own, and various ways of improving both the detection and treatment of
      depression accompanying physical illness are described. This paper is in four
      parts, the first dealing with the evidence for depression having a special
      relationship with physical disorders, the second dealing with detection of
      depression in physically ill patients, the third with the treatment of
      depression, and the fourth describing the advantages of treating depression among
      physically ill patients.

PMID- 20148150
TI  - Psychiatry in crisis? Back to fundamentals.

PMID- 20148149
TI  - Are psychiatrists an endangered species? Observations on internal and external
      challenges to the profession.
AB  - Based on recently voiced concerns about a crisis in psychiatry, six challenges to
      our profession are identified and discussed. As we approach the revisions of ICD
      10 and DSM-IV, the validity of psychiatry's diagnostic definitions and
      classification systems is increasingly questioned also from inside psychiatry. In
      addition, confidence in the results of therapeutic intervention studies is
      waning. A further challenge is the existence of de facto subgroups with opposing
      ideologies, a situation which is responsible for an unclear role profile of the
      psychiatrist. Challenges from outside include mounting patient and carer
      criticism, intrusion of other professions into psychiatry's traditional field of
      competence, and psychiatry's low status within medicine and in society in
      general. Studies suggest that the decline of the recruitment into psychiatry, as
      it is observed in many countries, might be related to problems arising from these
      challenges. It is unclear whether psychiatry will survive as a unitary medical
      discipline or whether those segments which are more rewarding, both financially
      and in status, will break away, leaving the unattractive tasks to carry out by
      what remains of psychiatry. The demise of the generalist and the rise of the
      specialist in modern society may contribute to this development. Attempts are
      underway by professional bodies to define the profile of a "general
      psychiatrist". Such discussions should be complemented by an analysis of the
      incentives which contribute to the centrifugal tendencies in psychiatry.

PMID- 20148151
TI  - Patients must be able to derive maximum benefit from a psychiatrist's medical
      skills and broad training.

PMID- 20148152
TI  - The golden years of psychiatry are in the future.

PMID- 20148153
TI  - Bridging a cultural divide within medicine: a role for psychiatrists?

PMID- 20148154
TI  - Psychiatry is alive and well.

PMID- 20148155
TI  - Psychiatry: a specialized profession or a medical specialty?

PMID- 20148156
TI  - Medicine, affect and mental health services.

PMID- 20148157
TI  - Psychiatry as a medical specialty: challenges and opportunities.

PMID- 20148158
TI  - Psychiatrists shall prevail.

PMID- 20148159
TI  - Psychiatry and the psychiatrist have a great future.

PMID- 20148160
TI  - Hypomania: a transcultural perspective.
AB  - This study examined the transcultural robustness of a screening instrument for
      hypomania, the Hypomania Checklist-32, first revised version (HCL-32 R1). It was
      carried out in 2606 patients from twelve countries in five geographic regions
      (Northern, Southern and Eastern Europe, South America and East Asia). In
      addition, GAMIAN Europe contributed data from its members. Exploratory and
      confirmatory factor analyses were used to examine the transregional stability of
      the measurement properties of the HCL-32 R1, including the influence of sex and
      age as covariates. Across cultures, a two-factor structure was confirmed: the
      first factor (F1) reflected the more positive aspects of hypomania (being more
      active, elated, self-confident, and cogni-tively enhanced); the second factor
      (F2) reflected the more negative aspects (being irritable, impulsive, careless,
      more substance use). The measurement properties of the HCL-32 R1 were largely
      invariant across cultures. Only few items showed transcultural differences in
      their relation to hypomania as measured by the test. F2 was higher among men and
      in more severe manic syndromes; F1 was highest in North and East Europe and
      lowest in South America. The scores decreased slightly with age. The frequency of
      the 32 items showed remarkable similarities across geographic areas, with two
      excep-tions: South Europeans had lower symptom frequencies in general and East
      Europeans higher rates of substance use. These findings support the interna
      tional applicability of the HCL-32 R1 as a screening instrument for hypomania.

PMID- 20148161
TI  - The prevalence and profile of non-affective psychosis in the Nigerian Survey of
      Mental Health and Wellbeing.
AB  - This study aimed to estimate the prevalence and correlates of non-affective
      psychosis among adult Nigerians. It was part of the Nigerian Survey of Mental
      Health and Wellbeing and was conducted in 8 out of the 22 states in Nigeria,
      representing about 22% of the national population. Face-to-face interviews with
      adults aged 18 years and over were administered using the WHO Composite
      International Diagnostic Interview, version 3 (CIDI.3). Clinical reappraisal was
      conducted by clinicians on a subsample of respondents. The CIDI.3 was found to
      have acceptable agreement with clinician-administered assessments, with kappa
      values ranging between 0.52 to 0.72, respectively, for narrowly-defined and broad
      categories of non-affective psychosis. The lifetime prevalence of non-affective
      psychosis was 2.1%, with visual hallucinations being the most commonly reported
      symptom and delusions of reference the least. Non-affective psy-chosis was
      significantly more common among urban dwellers. Persons with non-affective
      psychosis were at elevated risk to report both lifetime and 12-month comorbid DSM
      IV disorders as well as to experience impairment in basic and instrumental role
      functioning. Only a minority had received any treatment.

PMID- 20148162
TI  - Personality disorder: a new global perspective.
AB  - Personality disorder is now being accepted as an important condition in
      mainstream psychiatry across the world. Although it often remains unrecognized in
      ordinary practice, research studies have shown it is common, creates considerable
      morbidity, is associated with high costs to services and to society, and
      interferes, usually negatively, with progress in the treatment of other mental
      disorders. We now have evidence that personality disorder, as currently
      classified, affects around 6% of the world population, and the differences
      between countries show no consistent variation. We are also getting increasing
      evidence that some treatments, mainly psychological, are of value in this group
      of disorders. What is now needed is a new classification that is of greater value
      to clinicians, and the WPA Section on Personality Disorders is currently
      undertaking this task.

PMID- 20148163
TI  - Reports of my death from a brain cancer have not been evidence-based (at least so
      far).

PMID- 20148164
TI  - The Action Plan 2010 of the WPA Early Career Psychiatrists Council.

PMID- 20148166
TI  - WPA research fellowships.

PMID- 20148165
TI  - The WPA Regional Meeting in Abuja, Nigeria, 22-24 October 2009.

PMID- 20148167
TI  - Dual KS: Defining Gene Sets with Tissue Set Enrichment Analysis.
AB  - BACKGROUND: Gene set enrichment analysis (GSEA) is an analytic approach which
      simultaneously reduces the dimensionality of microarray data and enables ready
      inference of the biological meaning of observed gene expression patterns. Here we
      invert the GSEA process to identify class-specific gene signatures. Because our
      approach uses the Kolmogorov-Smirnov approach both to define class specific
      signatures and to classify samples using those signatures, we have termed this
      methodology "Dual-KS" (DKS). RESULTS: The optimum gene signature identified by
      the DKS algorithm was smaller than other methods to which it was compared in 5
      out of 10 datasets. The estimated error rate of DKS using the optimum gene
      signature was smaller than the estimated error rate of the random forest method
      in 4 out of the 10 datasets, and was equivalent in two additional datasets. DKS
      performance relative to other benchmarked algorithms was similar to its
      performance relative to random forests. CONCLUSIONS: DKS is an efficient analytic
      methodology that can identify highly parsimonious gene signatures useful for
      classification in the context of microarray studies. The algorithm is available
      as the dualKS package for R as part of the bioconductor project.

PMID- 20148168
TI  - Cardiovascular-CNS Comorbidity as a Means to Rationalize Serendipity in Drug
      Discovery and Advance Translational Research.

PMID- 20148169
TI  - A patient with unilateral tibial aplasia and accessory scrotum: a pure
      coincidence or nonfortuitous association?
AB  - Tibial aplasia is an uncommon lower limb malformation that can occur isolated or
      be part of a more complex malformation pattern. We describe a 9-year-old boy born
      after uneventful pregnancy and delivery. Family history was negative for maternal
      diabetes and other malformations. The patient presented with left tibial aplasia
      and homolateral prexial foot polydactyly. He also displayed enamel dysplasia and
      bifid scotum with cryptorchidism. Literature review failed to identify a
      significant syndromic association between lower limb defects of the tibial type
      and the genital anomalies reported here. The combination of tibial aplasia with
      midline genital malformations further supports the hypothesis that the tibial ray
      development mirrors the morphogenetic process of the radial structures.
      Accordingly, the malformation pattern observed in the present patient may be
      pathogenetically explained by an insult occurring during late blastogenesis.

PMID- 20148170
TI  - Adherence of Streptococcus mutans to Fiber-Reinforced Filling Composite and
      Conventional Restorative Materials.
AB  - OBJECTIVES.: The aim was to investigate the adhesion of Streptococcus mutans (S.
      mutans) to a short glass fibers reinforced semi-IPN polymer matrix composite
      resin. The effect of surface roughness on adhesion was also studied. For
      comparison, different commercial restorative materials were also evaluated.
      MATERIALS AND METHODS.: Experimental composite FC resin was prepared by mixing
      22.5 wt% of short E-glass fibers, 22.5 wt% of IPN-resin and 55 wt% of silane
      treated silica fillers using high speed mixing machine. Three direct composite
      resins (Z250, Grandio and Nulite), resin-modified glass ionomers (Fuji II LC),
      amalgam (ANA 2000), fiber-reinforced composite (FRC) (everStick and Ribbond), and
      pre-fabricated ceramic filling insert (Cerana class 1) were tested in this study.
      Enamel and dentin were used as controls. The specimens (n=3/group) with or
      without saliva were incubated in a suspension of S. mutans allowing initial
      adhesion to occur. For the enumeration of cells on the disc surfaces as colony
      forming units (CFU) the vials with the microbe samples were thoroughly Vortex
      treated and after serial dilutions grown anaerobically for 2 days at +37 degrees
      C on Mitis salivarius agars (Difco) containing bacitracin. Bacterial adhesion was
      also evaluated by using scanning electron microscopy. Surface roughness (Ra) of
      the materials was also determined using a surface profilometer. All results were
      statistically analyzed with one-way analysis of variance (ANOVA). RESULTS.:
      Composite FC resin and other commercial restorative materials showed similar
      adhesion of S. mutans, while adhesion to dentin and enamel was significantly
      higher (p<0.05). Surface roughness had no effect on bacterial adhesion. Saliva
      coating significantly decreased the adhesion for all materials (p<0.05).
      Composite FC resin had a significantly higher Ra value than control groups
      (p<0.05). CONCLUSIONS.: Short fiber-reinforced composite with semi-IPN polymer
      matrix revealed similar S. mutans adhesion than commercial restorative materials.

PMID- 20148171
TI  - Isolation and characterization of a novel facultative anaerobic filamentous
      fungus from Japanese rice field soil.
AB  - A novel filamentous fungus strain designated RB-1 was isolated into pure culture
      from Japanese rice field soil through an anaerobic role tube technique. The
      strain is a mitosporic fungus that grows in both aerobic and strict anaerobic
      conditions using various mono-, di-, tri-, and polysaccharides with acetate and
      ethanol productions. The amount of acetate produced was higher than that of
      ethanol in both aerobic and anaerobic cultures. The characteristic verrucose or
      punctuate conidia of RB-1 closely resembled those of some strains of the genus
      Thermomyces, a thermophilic or mesophilic anamorphic ascomycete. However, based
      on phylogenetic analysis with the small subunit (SSU) and large subunit (LSU)
      rDNA sequences, RB-1 was characterized as a member of the class Lecanoromycetes
      of the phylum Ascomycota. Currently, RB-1 is designated as an anamorphic
      ascomycete and is phylogenetically considered an incertae sedis within the class
      Lecanoromycetes.

PMID- 20148172
TI  - Neurological examination of the upper limb: a study of construct validity.
AB  - OBJECTIVE: We have previously demonstrated that neurological individual findings
      and patterns can be reliably assessed in the examination of the upper limb and
      also that they are related to pain, weakness, and/or numbness/tingling. This
      study aimed to study further aspects of the construct validity of the
      neurological examination. METHODS: Blinded to patient-characteristics, two
      examiners assessed the function of 16 muscles, the sensibility in 7 territories,
      and the nerve-mechanosensitivity at 20 locations in 82 upper limbs. Based on
      anatomical patterns and pre-designed algorithms, one or both examiners rated
      neuropathy as "possible" or "definite" in 40 limbs and also determined the
      location( s). We developed and tested hypotheses on anatomically and regionally
      related locations of nerve afflictions (a selective vulnerability of neurons,
      double and multiple crush, and a tendency to regional spread) and examined the
      stability of the internal structure of the constructs in different situations.
      The interrelations of findings were analyzed by hypothesis testing and factor
      analyses, and the homogeneity of location profiles was analyzed by a conditional
      likelihood test. RESULTS: Out of 30 limbs with related locations of neuropathy,
      the findings of each examiner correlated positively (gamma > 0.35) in 22/25,
      respectively. The patterns of the interrelations identified by the two examiners
      were similar, with no evidence of any heterogeneity of location profiles for
      either examiner. CONCLUSIONS: This study supports the validity of the physical
      examination. However, feasibility of its application requires the demonstration
      of further aspects of construct validity and a favorable influence on patient
      management and/or prevention.

PMID- 20148173
TI  - Effects of aging and cyclosporin a on collagen turnover in human gingiva.
AB  - BACKGROUND: WE AIMED AT CHARACTERIZING THE AGING GINGIVA ANALYZING: i) collagen
      content and turnover in human gingival tissues and fibroblasts obtained from
      healthy young and aging subjects. ii) the effect of cyclosporin A administration
      in human cultured gingival fibroblasts obtained from aging compared to young
      subjects. METHODS: Morphological analysis was performed on haematoxylin-eosin and
      Sirius red stained paraffin-embedded gingival biopsies from young and aging
      healthy subjects. The expression of the main genes and proteins involved in
      collagen turnover were determined by real time PCR, dot blot and SDS-zymography
      on cultured young and aging gingival fibroblasts, and after cyclosporin A
      administration. RESULTS: Our results suggest that in healthy aged people,
      gingival connective tissue is characterized by a similar collagen content and
      turnover. Collagen turnover pathways are similarly affected by cyclosporin A
      treatment in young and aging gingival fibroblasts. CONCLUSIONS: Cyclosporin A
      administration affects gingival collagen turnover pathways in young and aging
      fibroblasts at the same extent, suggesting that during aging cyclosporin A
      administration is not related to relevant collagen turnover modifications.

PMID- 20148174
TI  - Purification of an Exopolygalacturonase from Penicillium viridicatum RFC3
      Produced in Submerged Fermentation.
AB  - An exo-PG obtained from Penicillium viridicatum in submerged fermentation was
      purified to homogeneity. The apparent molecular weight of the enzyme was 92 kDa,
      optimum pH and temperature for activity were pH 5 and 50-55 degrees C. The exo-PG
      showed a profile of an exo-polygalacturonase, releasing galacturonic acid by
      hydrolysis of pectin with a high degree of esterification (D.E.). Ions Ca(2+)
      enhanced the stability of enzyme and its activity by 30%. The K(m) was 1.30 in
      absence of Ca(2+) and 1.16 mg mL(-1) in presence of this ion. In relation to the
      V(max) the presence of this ion increased from 1.76 to 2.07 mumol min(-1)mg(-1).

PMID- 20148175
TI  - Correlation between Group B Streptococcal Genotypes, Their Antimicrobial
      Resistance Profiles, and Virulence Genes among Pregnant Women in Lebanon.
AB  - The antimicrobial susceptibility profiles of 76 Streptococcus agalactiae (Group B
      Streptococci [GBS]) isolates from vaginal specimens of pregnant women near term
      were correlated to their genotypes generated by Random Amplified Polymorphic DNA
      analysis and their virulence factors encoding genes cylE, lmb, scpB, rib, and bca
      by PCR. Based on the distribution of the susceptibility patterns, six profiles
      were generated. RAPD analysis detected 7 clusters of genotypes. The cylE gene was
      present in 99% of the isolates, the lmb in 96%, scpB in 94.7%, rib in 33%, and
      bca in 56.5% of isolates. The isolates demonstrated a significant correlation
      between antimicrobial resistance and genotype clusters denoting the distribution
      of particular clones with different antimicrobial resistance profiles, entailing
      the practice of caution in therapeutic options. All virulence factors encoding
      genes were detected in all seven genotypic clusters with rib and bca not
      coexisting in the same genome.

PMID- 20148176
TI  - Coupling Constant pH Molecular Dynamics with Accelerated Molecular Dynamics.
AB  - An extension of the constant pH method originally implemented by Mongan et al.
      (J. Comput. Chem.2004, 25, 2038-2048) is proposed in this study. This adapted
      version of the method couples the constant pH methodology with the enhanced
      sampling technique of accelerated molecular dynamics, in an attempt to overcome
      the sampling issues encountered with current standard constant pH molecular
      dynamics methods. Although good results were reported by Mongan et al. on
      application of the standard method to the hen egg-white lysozyme (HEWL) system,
      residues which possess strong interactions with neighboring groups tend to
      converge slowly, resulting in the reported inconsistencies for predicted pK(a)
      values, as highlighted by the authors. The application of the coupled method
      described in this study to the HEWL system displays improvements over the
      standard version of the method, with the improved sampling leading to faster
      convergence and producing pK(a) values in closer agreement to those obtained
      experimentally for the more slowly converging residues.

PMID- 20148177
TI  - Regulation of hormonal therapy resistance by cell cycle machinery.
AB  - Estrogen Receptor (ER) plays a central role in the development and progression of
      breast cancer. Hormonal therapy substantially improves disease-free survival of
      ER+ve breast tumors, however acquired resistance to endocrine therapies
      frequently occur. Emerging data implicate growth factor signaling pathways and
      their cross talk with ER as major cause of resistance. Both these pathways have
      been recently shown to use cell cycle machinery as downstream effectors in
      mediating therapy resistance. Several studies have demonstrated deregulation of
      cell cycle regulators and their cross talk with ER in therapy resistant tumors.
      The objective of this article is to review the underlying mechanisms by which
      tumor cells use cell cycle machinery to override hormonal therapy and to explore
      cell cycle machinery components as novel therapy targets for overcoming hormonal
      therapy resistance.

PMID- 20148178
TI  - Isolation of highly pathogenic avian influenza H5N1 virus from Saker falcons
      (Falco cherrug) in the Middle East.
AB  - There is accumulating evidence that birds of prey are susceptible to fatal
      infection with highly pathogenic avian influenza (HPAI) virus. We studied the
      antigenic, molecular, phylogenetic, and pathogenic properties of 2 HPAI H5N1
      viruses isolated from dead falcons in Saudi Arabia and Kuwait in 2005 and 2007,
      respectively. Phylogenetic and antigenic analyses grouped both isolates in clade
      2.2 (Qinghai-like viruses). However, the viruses appeared to have spread westward
      via different flyways. It remains unknown how these viruses spread so rapidly
      from Qinghai after the 2005 outbreak and how they were introduced into falcons in
      these two countries. The H5N1 outbreaks in the Middle East are believed by some
      to be mediated by wild migratory birds. However, sporting falcons may be at
      additional risk from the illegal import of live quail to feed them.

PMID- 20148180
TI  - HEREDITARY MYELOPATHIES.
AB  - Hereditary myelopathies are a diverse group of disorders in which major aspects
      of the clinical syndrome involve spinal cord structures. Hereditary myelopathic
      syndromes can be recognized as four clinical paradigms: (1) spinocerebellar
      ataxia, (2) motor neuron disorder, (3) leukodystrophy, and (4) distal motor
      sensory axonopathy. This review illustrates these hereditary myelopathy paradigms
      with clinical examples with an emphasis on clinical recognition and differential
      diagnosis.

PMID- 20148181
TI  - Identifying Conserved and Divergent Transcriptional Modules by Cross-species
      Matrix Decomposition on Microarray Data.
AB  - Cross-species comparison of gene expression profiles allows deciphering
      fundamental and species-specific transcriptional programs of cells and offers
      insight into organization and evolution of the genome and genetic network. Here,
      we propose an algorithm for comparing microarray data from different species to
      unravel transcriptional modules that are conserved or divergent through
      evolution. The proposed algorithm is based on cross-species matrix decomposition
      that includes a nonlinear independent component analysis followed a generalized
      probabilistic sparse matrix factorization on microarray data from different
      species. The proposed algorithm captures transcriptional modularity that might
      result from highly nonlinear interactions among genes, and partitions genes into
      mutually non-exclusive transcriptional modules. The conserved transcriptional
      modules are identified by the latent variables that are associated with
      predominant biological prototypes shared across species. We illustrated the
      application of the proposed algorithm by an analysis of human and mouse embryonic
      stem cell (ESC) data. The analysis uncovered conserved and divergent
      transcriptional modules in the ESC transcriptomes, shedding light on the
      understanding of fundamental and species-specific regulatory mechanisms
      controlling ESC development.

PMID- 20148179
TI  - Nicotinic Receptors: Role in Addiction and Other Disorders of the Brain.
AB  - Nicotine, the addictive component of cigarette smoke has profound effects on the
      brain. Activation of its receptors by nicotine has complex consequences for
      network activity throughout the brain, potentially contributing to the addictive
      property of the drug. Nicotinic receptors have been implicated in psychiatric
      illnesses like schizophrenia and are also neuroprotective, potentially beneficial
      for neurodegenerative diseases. These effects of nicotine serve to emphasize the
      multifarious roles the drug, acting through multiple nicotinic acetylcholine
      receptor subtypes. The findings also remind us of the complexity of signaling
      mechanisms and stress the risks of unintended consequences of drugs designed to
      combat nicotine addiction.

PMID- 20148182
TI  - Sensitive electrochemical detection of horseradish peroxidase at disposable
      screen-printed carbon electrode.
AB  - A rapid, simple and sensitive electrochemical assay of horseradish peroxidase
      (HRP) performed on disposable screen-printed carbon electrode was developed. HRP
      activities were monitored by square-wave voltammetric (SWV) measuring the
      electroactive enzymatic product in the presence of o-aminophenol and hydrogen
      peroxide substrate solution. SWV analysis demonstrated a greater sensitivity and
      shorter analysis time than the widely used amperometric and differential-pulsed
      voltammetric methods. The voltammetric characteristics of substrate and enzymatic
      product as well as the parameters of SWV analysis were optimized. Under optimized
      conditions, a linear response for HRP from 0.003 - 0.1 U/mL and a detection limit
      of 0.002 U/mL (1.25*10(-15) mol in 25 MUL) were obtained with a good precision
      (RSD = 8%; n = 6). This rapid and sensitive HRP assay with microliters-assay
      volume could be readily integrated to portable devices and point-of-care (POC)
      diagnosis applications.

PMID- 20148183
TI  - Psychopathy and violence: increasing specificity.
AB  - A large body of literature has established that the construct of psychopathy is
      broadly related to violence, and the clinical application of the psychopathy
      construct as a predictor of violence appears to be increasing. This increased
      application warrants further specification of this relationship. That is, it may
      be important to identify factors that moderate relationships between psychopathy
      and violence, and to determine the extent to which subcomponents of the syndrome
      account for the relationships between psychopathy and specific types of violence.
      The present review summarises initial attempts to address these goals. We begin
      by summarising recent trends in the forensic application of the psychopathy
      construct. We then examine evidence bearing on the extent to which the predictive
      power of psychopathy for violence is moderated by other factors. Finally, we
      examine relationships between subcomponents of the psychopathy construct and
      specific types of violent and aggressive behaviour to examine whether
      relationships between psychopathy and violence are accounted for by specific
      components of psychopathy.

PMID- 20148184
TI  - Surgeon Perceptions of Minimally Invasive Spine Surgery.
AB  - BACKGROUND: Interest in minimally invasive surgery (MIS) of the spine has driven
      the development of new and innovative techniques to treat an ever wider range of
      spinal disorders. Despite these new advances, spine surgeons have been slow in
      adopting MIS into their clinical practice. This study aims to provide a better
      understanding of the factors that have led to limited incorporation of these
      procedures into their practices. METHODS: Eighty-seven spine surgeons completed a
      questionnaire related to their perceptions of MIS. Respondents were asked to
      comment on their perceptions regarding the limitations and advantages of
      minimally invasive spine surgery. Survey results were then analyzed for both
      overall opinions and opinions based on the amount of MIS utilization in the
      respondents' current practices. RESULTS: The top 3 identified limitations of MIS
      of the spine were technical difficulty, lack of convenient training
      opportunities, and radiation exposure. Of these respondents, spine surgeons
      experienced in MIS were concerned more with radiation exposure than the lack of
      training opportunities. In contrast, spine surgeons with little MIS experience
      cited the lack of training opportunities as the most significant limitation.
      There was little concern related to the limited proven clinical efficacy of MIS
      of the spine. DISCUSSION: Technical factors, training opportunities, and
      radiation exposure appear to be the major obstacles to MIS of the spine. Most
      spine surgeons believe that MIS leads to faster return to daily activities,
      better long-term function, and decreased hospitalization. This may explain why
      most surgeons did not cite a lack of proven efficacy as a major limitation to
      MIS. These findings indicate that the widespread adoption of MIS of the spine
      will likely be driven through relatively simple means, such as improved training
      programs that strive to decrease the technical difficulty and limit radiation
      exposure of these procedures. It is unlikely that extensive clinical data alone,
      without such improved training programs, will be sufficient to drive widespread
      use of minimally invasive spine surgery.

PMID- 20148185
TI  - Enhancing the Attitudes and Self-Efficacy of Older Adults Toward Computers and
      the Internet: Results of a Pilot Study.
AB  - This pilot study explored whether a manualized computer and Internet training
      program could enhance older adults' computer self-efficacy and attitudes toward
      computers and the Internet. A total of 32 community-dwelling adults 65 years of
      age or older were randomly assigned to either an experimental or control group,
      with each group consisting of 8 women and 8 men. The experimental group received
      6 weeks of training with 2-hour one-on-one sessions once per week. The same
      training was administered to the control group upon completion of the post-test,
      6 weeks after the baseline assessment, to match the procedures on all counts with
      the exception of training administration. The results of two ANCOVAs indicated
      that participants within the experimental group improved significantly on both
      their computer self-efficacy (p < .001) and attitudinal scores (p < .001) at the
      post-training assessment. No improvements were found in the control group.

PMID- 20148186
TI  - Effect of Saline Water Irrigation on Growth and Physiological Responses of Three
      Rose Rootstocks.
AB  - Salt-tolerant landscape plants are needed for arid and semiarid regions where the
      supply of quality water is limited and soil salinization often occurs. This study
      evaluated growth, chloride (Cl) and sodium (Na) uptake, relative chlorophyll
      content, and chlorophyll fluorescence of three rose rootstocks [Rosa *fortuniana
      Lindl., R. multiflora Thunb., and R. odorata (Andr.) Sweet] irrigated with saline
      solutions at 1.6 (control), 3.0, 6.0, or 9.0 dS.m (-1) electrical conductivity in
      a greenhouse. After 15 weeks, most plants in 9.0 dS.m (-1) treatment died
      regardless of rootstock. Significant growth reduction was observed in all
      rootstocks at 6.0 dS.m (-1) compared with the control and 3.0 dS.m (-1), but the
      reduction in R. *fortuniana was smaller than in the other two rootstocks. The
      visual scores of R. multiflora at 3.0 and 6.0 dS.m(-1) were slightly lower than
      those of the other rootstocks. Rosa odorata had the highest shoot Na
      concentration followed by R. multiflora; however, R. multiflora had the highest
      root Na concentration followed by R. odorata. All rootstocks had higher Cl
      accumulation in all plant parts at elevated salinities, and no substantial
      differences in Cl concentrations in all plant parts existed among the rootstocks,
      except for leaf Cl concentration in R. multiflora, which was higher than those in
      the other two rootstocks. The elevated salinities of irrigation water reduced the
      relative chlorophyll concentration, measured as leaf SPAD readings, and maximal
      photochemical efficiency of photosystem II (PSII) and minimal fluorescence
      (F(0))/maximum fluorescence (F(v)/F(m)), but the largest reduction in F(v)/F(m)
      was only 2.4%. Based on growth and visual quality, R. *fortuniana was relatively
      more salt-tolerant than the other two rootstocks and R. odorata was slightly more
      salt-tolerant than R. multiflora.

PMID- 20148187
TI  - Human and animal sentinels for shared health risks.
AB  - The tracking of sentinel health events in humans in order to detect and manage
      disease risks facing a larger population is a well accepted technique applied to
      influenza, occupational conditions, and emerging infectious diseases. Similarly,
      animal health professionals routinely track disease events in sentinel animal
      colonies and sentinel herds. The use of animals as sentinels for human health
      threats, or of humans as sentinels for animal disease risk, dates back at least
      to the era when coal miners brought caged canaries into mines to provide early
      warning of toxic gases. Yet the full potential of linking animal and human health
      information to provide warning of such "shared risks" from environmental hazards
      has not been realized. Reasons appear to include the professional segregation of
      human and animal health communities, the separation of human and animal
      surveillance data, and evidence gaps in the linkages between human and animal
      responses to environmental health hazards. The One Health initiative and growing
      international collaboration in response to pandemic threats, coupled with
      development the fields of informatics and genomics, hold promise for improved
      sharing of knowledge about sentinel events in order to detect and reduce
      environmental health threats shared between species.

PMID- 20148188
TI  - Role and development of GLP-1 receptor agonists in the management of diabetes.
AB  - Glucagon-like peptide-1 (GLP-1) is a hormone secreted from enteroendocrine L
      cells of the intestine in response to food. Exogenous GLP-1 administration at
      pharmacological doses results in many effects that are beneficial for treating
      type 2 diabetes, these include: (1) an increase in insulin secretion from beta
      cells; (2) a suppression of glucagon secretion from alpha cells in the presence
      of hyperglycemia but not hypoglycemia; (3) a delay in gastric emptying and gut
      motility which in turns delays absorption of ingested nutrients and dampens post
      prandial glucose excursion; and (4) an increase in the duration of postprandial
      satiety therefore suppressing appetite and decreasing food intake which
      eventually leads to weight loss. However, GLP-1 is subject to rapid enzymatic
      degradation, and therefore, not suitable for long-term treatment. A synthetic
      enzyme-resistant GLP-1 receptor agonist that reproduces the biological effects of
      GLP-1 is in use and more are under development. This review aims at providing a
      summary of the properties of GLP-1 and the development of GLP-1-based therapies
      for treatment of diabetes.

PMID- 20148190
TI  - On large margin hierarchical classification with multiple paths.
AB  - Hierarchical classification is critical to knowledge management and exploration,
      as in gene function prediction and document categorization. In hierarchical
      classification, an input is classified according to a structured hierarchy. In a
      situation as such, the central issue is how to effectively utilize the inter
      class relationship to improve the generalization performance of flat
      classification ignoring such dependency. In this article, we propose a novel
      large margin method through constraints characterizing a multi-path hierarchy,
      where class membership can be non-exclusive. The proposed method permits a
      treatment of various losses for hierarchical classification. For implementation,
      we focus on the symmetric difference loss and two large margin classifiers:
      support vector machines and psi-learning. Finally, theoretical and numerical
      analyses are conducted, in addition to an application to gene function
      prediction. They suggest that the proposed method achieves the desired objective
      and outperforms strong competitors in the literature.

PMID- 20148191
TI  - A Partial Nudged Elastic Band Implementation for Use with Large or Explicitly
      Solvated Systems.
AB  - The nudged elastic band method (NEB) can be used to find a minimum energy path
      between two given starting structures. This method has been available in the
      standard release of the Amber9 and Amber10 suite of programs. In this paper a
      novel implementation of this method will be discussed, in which the nudged
      elastic band method is applied to only a specific, user-defined subset of atoms
      in a particular system, returning comparable results and minimum energy pathways
      as the standard implementation for an alanine dipeptide test system. This allows
      incorporation of explicit solvent with simulated systems, which may be preferred
      in many cases to an implicit solvent model. From a computational standpoint, this
      implementation of NEB also reduces the communication overhead inside the code,
      resulting in better performance for larger systems.

PMID- 20148189
TI  - MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory
      mediators IL-6 and IL-8.
AB  - Senescence is a cellular program that irreversibly arrests the proliferation of
      damaged cells and induces the secretion of the inflammatory mediators IL- 6 and
      IL-8 which are part of a larger senescence associated secretory phenotype (SASP).
      We screened quiescent and senescent human fibroblasts for differentially
      expressed microRNAS (miRNAs) and found that miRNAs 146a and 146b (miR-146a/b)
      were significantly elevated during senescence. We suggest that delayed miR-146a/b
      induction might be a compensatory response to restrain inflammation. Indeed,
      ectopic expression of miR-146a/b in primary human fibroblasts suppressed IL-6 and
      IL-8 secretion and downregulated IRAK1, a crucial component of the IL-1 receptor
      signal transduction pathway. Cells undergoing senescence without induction of a
      robust SASP did not express miR-146a/b. Further, IL-1alpha neutralizing
      antibodies abolished both miR-146a/b expression and IL-6 secretion. Our findings
      expand the biological contexts in which miRNA-146a/b modulates inflammatory
      responses. They suggest that IL-1 receptor signaling initiates both miR-146a/b
      upregulation and cytokine secretion, and that miR-146a/b is expressed in response
      to rising inflammatory cytokine levels as part of a negative feedback loop that
      restrains excessive SASP activity.

PMID- 20148192
TI  - A Test of Problem Behavior and Self-Medication Theories in Incarcerated
      Adolescent Males.
AB  - The purpose of this study is to examine the problem behavior and self-medication
      models of alcohol abuse in incarcerated male adolescents. Male adolescents (N =
      56) incarcerated in a juvenile correction facility were administered a battery of
      psychological measures. Approximately 84% of adolescents with clinically
      significant alcohol-related problems prior to incarceration indicated use of
      alcohol for purposes of self-medication and 73% indicated that their alcohol use
      was associated with aggressive and rebellious behavior. Further, adolescents with
      clinically significant alcohol-related problems prior to incarceration reported
      higher levels of affective symptoms, mood-related cognitive distortion, and less
      use of social support during incarceration than adolescents without clinically
      significant alcohol-related problems. They also reported more symptoms associated
      with oppositional defiant but not conduct disorder. For the majority of
      incarcerated male adolescents in this sample, alcohol-related problems appeared
      to be associated with both self-medication and problem behavior. Incarcerated
      adolescents with a history of alcohol-related problems may require skills
      training in addition to substance abuse services to address affective symptoms
      and coping skill deficits.

PMID- 20148193
TI  - Predicting Type 1 Diabetes Candidate Genes using Human Protein-Protein
      Interaction Networks.
AB  - BACKGROUND: Proteins directly interacting with each other tend to have similar
      functions and be involved in the same cellular processes. Mutations in genes that
      code for them often lead to the same family of disease phenotypes. Efforts have
      been made to prioritize positional candidate genes for complex diseases utilize
      the protein-protein interaction (PPI) information. But such an approach is often
      considered too general to be practically useful for specific diseases. RESULTS:
      In this study we investigate the efficacy of this approach in type 1 diabetes
      (T1D). 266 known disease genes, and 983 positional candidate genes from the 18
      established linkage loci of T1D, are compiled from the T1Dbase
      (http://t1dbase.org). We found that the PPI network of known T1D genes has
      distinct topological features from others, with significantly higher number of
      interactions among themselves even after adjusting for their high network degrees
      (p<1e-5). We then define those positional candidates that are first degree PPI
      neighbours of the 266 known disease genes to be new candidate disease genes. This
      leads to a list of 68 genes for further study. Cross validation using the known
      disease genes as benchmark reveals that the enrichment is ~17.1 fold over random
      selection, and ~4 fold better than using the linkage information alone. We find
      that the citations of the new candidates in T1D-related publications are
      significantly (p<1e-7) more than random, even after excluding the co-citation
      with the known disease genes; they are significantly over-represented (p<1e-10)
      in the top 30 GO terms shared by known disease genes. Furthermore, sequence
      analysis reveals that they contain significantly (p<0.0004) more protein domains
      that are known to be relevant to T1D. These findings provide indirect validation
      of the newly predicted candidates. CONCLUSION: Our study demonstrates the
      potential of the PPI information in prioritizing positional candidate genes for
      T1D.

PMID- 20148195
TI  - EXCLUSION LEARNING AND EMERGENT SYMBOLIC CATEGORY FORMATION IN INDIVIDUALS WITH
      SEVERE LANGUAGE IMPAIRMENTS AND INTELLECTUAL DISABILITIES.
AB  - We evaluated formation of simple symbolic categories from initial learning of
      specific dictated word-picture relations through emergence of untaught or derived
      relations. Participants were 10 individuals with severe intellectual and language
      limitations. Three experimental categories were constructed, each containing 1
      spoken word (Set A), 1 photograph (Set B), and 1 visual-graphic "lexigram" (Set
      C). Exclusion-based learning procedures were used to teach first the 3 auditory
      visual relations (A-B relations) and then the 3 visual-visual relations (B-C
      relations) for each category. Seven participants acquired these initial
      relations. The untaught relations C-B and A-C were then assessed to evaluate the
      emergence of symbolic categories. Participants demonstrated virtually error-free
      performances on C-B and A-C derived relations. The study helps to define
      operationally a highly useful procedural path for systematic instruction in
      symbolic functioning for persons with intellectual and language disabilities
      associated with autism and other neurodevelopmental disorders.

PMID- 20148196
TI  - Attenuation map estimation with SPECT emission data only.
AB  - Quantitative SPECT can be well achieved if photon attenuation is taken into
      account in the reconstruction process. Using a transmission scan is a common
      approach. A dramatic simplification could be made if the attenuation map could be
      obtained from the emission data. In this paper, we propose a new method to
      estimate the attenuation map using the data consistency conditions of the
      attenuated Radon transform. It is based on deriving boundaries of the constant
      regions of the true attenuation map using an iterative algorithm. This new method
      is tested by Monte Carlo simulations with the attenuation and scattering effects.

PMID- 20148194
TI  - Defining an Embedded Code for Protein Ubiquitination.
AB  - It has been more than 30 years since the initial report of the discovery of
      ubiquitin as an 8.5 kDa protein of unknown function expressed universally in
      living cells. And still, protein modification by covalent conjugation of the
      ubiquitin molecule is one of the most dynamic posttranslational modifications
      studied in terms of biochemistry and cell physiology. Ubiquitination plays a
      central regulatory role in number of eukaryotic cellular processes such as
      receptor endocytosis, growth-factor signaling, cell-cycle control, transcription,
      DNA repair, gene silencing, and stress response. Ubiquitin conjugation is a three
      step concerted action of the E1-E2-E3 enzymes that produces a modified protein.
      In this review we investigate studies undertaken to identify both ubiquitin and
      SUMO (small ubiquitin-related modifier) substrates with the goal of understanding
      how lysine selectivity is achieved. The SUMOylation pathway though distinct from
      that of ubiquitination, draws many parallels. Based upon the recent findings, we
      present a model to explain how an individual ubiquitin ligase may target specific
      lysine residue(s) with the co-operation from a scaffold protein.

PMID- 20148197
TI  - ESTIMATING THE GUMBEL SCALE PARAMETER FOR LOCAL ALIGNMENT OF RANDOM SEQUENCES BY
      IMPORTANCE SAMPLING WITH STOPPING TIMES.
AB  - The gapped local alignment score of two random sequences follows a Gumbel
      distribution. If computers could estimate the parameters of the Gumbel
      distribution within one second, the use of arbitrary alignment scoring schemes
      could increase the sensitivity of searching biological sequence databases over
      the web. Accordingly, this article gives a novel equation for the scale parameter
      of the relevant Gumbel distribution. We speculate that the equation is exact,
      although present numerical evidence is limited. The equation involves ascending
      ladder variates in the global alignment of random sequences. In global alignment
      simulations, the ladder variates yield stopping times specifying random sequence
      lengths. Because of the random lengths, and because our trial distribution for
      importance sampling occurs on a different sample space from our target
      distribution, our study led to a mapping theorem, which led naturally in turn to
      an efficient dynamic programming algorithm for the importance sampling weights.
      Numerical studies using several popular alignment scoring schemes then examined
      the efficiency and accuracy of the resulting simulations.

PMID- 20148198
TI  - Controlling Affinity Binding with Peptide-Functionalized Poly(ethylene glycol)
      Hydrogels.
AB  - Poly(ethylene glycol) (PEG) hydrogels functionalized with peptide moieties have
      been widely used in regenerative medicine applications. While many studies have
      suggested the importance of affinity binding within PEG hydrogels, the
      relationships between the structures of the peptide motifs and their binding to
      protein therapeutics remain largely unexplored, especially in the recently
      developed thiol-acrylate photopolymerization systems. Herein, we employ Forster
      resonance energy transfer (FRET) and thiol-acrylate photopolymerizations to
      investigate how the architectures of affinity peptides in crosslinked hydrogels
      affect their binding to diffusible proteins. The binding between diffusible
      streptavidin and biotinylated peptide immobilized to PEG hydrogel network was
      used as a model system to reveal the interplay between affinity binding and
      peptide sequences/architectures. In addition, we design peptides with different
      structures to enhance affinity binding within PEG hydrogels and to provide
      tunable affinity-based controlled delivery of basic fibroblast growth factor
      (bFGF). This study demonstrates the importance of affinity binding in controlling
      the availability of hydrogel-encapsulated proteins and provides strategies for
      enhancing affinity binding of protein therapeutics to bound peptide moieties in
      thiol-acrylate photopolymerized PEG hydrogels. The results presented herein
      should find useful on the design and fabrication of hydrogels to retain and
      sustained release of growth factors for promoting tissue regeneration.

PMID- 20148201
TI  - Silicon clathrates and carbon analogs: high pressure synthesis, structure, and
      superconductivity.
AB  - Compounds with cage-like structures of elemental silicon and carbon are
      comparatively reviewed. Barium containing silicon clathrate compounds isomorphous
      with type I gas hydrates were prepared using high pressure and high temperature
      (HPHT) conditions, and found to become superconductors. The application of HPHT
      conditions to Zintl binary silicides have produced a number of silicon-rich cage
      like structures including new clathrate structures; most of them are
      superconductors. Carbon analogs of silicon clathrates can be prepared by 3D
      polymerization of C(60) under HPHT conditions, which are new allotropes of carbon
      with expanded framework structures. The crystal chemistry and characteristic
      properties of some related compounds are also reviewed.

PMID- 20148202
TI  - Hydrothermal syntheses and characterizations of two novel frameworks constructed
      from polyoxometalates, metals and organic units.
AB  - Two novel compounds have been hydrothermally synthesized and characterized by IR
      spectra and single crystal X-ray diffraction analyses. Crystal structure analyses
      reveal that and exhibit novel 2-D framework structures constructed from tungsten
      polyoxoanions, metal ions and 4,4-byp units, respectively.

PMID- 20148203
TI  - Frustrated Lewis pairs: reactivities of TMS protected amines and phosphines in
      the presence of B(C(6)F(5))(3).
AB  - TMS protected amines in combination with B(C(6)F(5))(3) were found to activate
      H(2) and this is followed by a cleavage of the N-Si bond and the generation of
      TMSH. A TMS protected phosphine on the other hand reacts rapidly with
      B(C(6)F(5))(3) to give the known compound tBu(2)P(C(6)F(4))B(C(6)F(5))(2) by a
      facile and efficient route.

PMID- 20148204
TI  - Si-C bond activation in the reaction of first generation Grubbs' catalyst with
      alkynylsilanes - formation of [Cl(2){P(C(6)H(11))(3)}(2)Ru(=CHCH=CHPh)]
      anddisiloxanes.
AB  - The first generation Grubbs catalyst [Cl(2){P(C(6)H(11))(3)}(2)Ru=C(H)Ph] reacts
      efficiently with alkynylsilanes in the presence of water to give the styryl
      carbene complex [Cl(2){P(C(6)H(11))}(2) Ru=C(CH=CHPh)H] and disiloxane.

PMID- 20148205
TI  - "Click" labeling strategy for M(CO)(3) (M = Re, (99m)Tc) prostate cancer targeted
      flutamide agents.
AB  - Two distinct "click" chemistry labeling approaches were investigated with
      dipyridylamine alkyne derivatives and M(CO)(3)(+) (M = Re, (99m)Tc). The triazole
      ring was found uncoordinated and was incorporated into the preparation of a
      crossover androgen receptor targeting inhibitor for prostate cancer.

PMID- 20148206
TI  - Rhodium-P,O-bidentate coordinated ureaphosphine ligands for asymmetric
      hydrogenation reactions.
AB  - We present new ureaphosphine ligands that coordinate in a P,O-bidentate fashion
      to rhodium(i). The ureaphosphine-Rh(i)-complexes were effectively used in the
      asymmetric hydrogenation of cyclic enamides giving high conversions and
      enantioselectivity.

PMID- 20148207
TI  - Zinc complexes of the carbahemiporphyrazines.
AB  - Zinc can be inserted into the carbahemiporphyrazines by use of the organometallic
      reagent diethylzinc; in the case of benziphthalocyanine, concomitant alkylation
      of an alpha-carbon position and metalation occurs.

PMID- 20148209
TI  - Amalgamating metalloligands with coordination networks.
AB  - The O(4)-cavity in [Cu{(R,R)-}] ((R,R)-H(2) = 1,6-bis(3-ethoxy-2-hydroxyphenyl)
      (3R,4R)-(-)-cyclohexane-1,2-diyl-2,5-diazahexa-1,5-diene) binds HgBr(2) to give P
      and M-[Cu{(R,R)-}HgBr(2)]. In the solid state, there is no diastereoselectivity
      with respect to the handedness of the helical twist adopted by the coordinated
      Schiff base ligand and [Cu{(R,R)-}HgBr(2)] crystallizes with two independent
      molecules possessing M- and P-chirality, respectively, in the asymmetric unit.
      Single crystal structural data confirm that the same phenomenon is observed when
      [Ni{(R,R)-}] is treated with HgBr(2)or Hg(CN)(2). However, when an excess of
      Hg(NO(3))(2).H(2)O reacts with [Cu{(R,R)-}], C-mercuration occurs in both 3
      ethoxy-2-hydroxyphenyl rings in addition to the coordination of a Hg(NO(3))(2)
      unit within the O(4)-cavity of [Cu{(R,R)-}]. This results in the formation of a
      two-dimensional coordination polymer network. The direct C-mercuration of a
      coordinated Schiff base ligand is not unique to the ligand in [Cu{(R,R)-}], but
      also occurs during the reaction of [Cu(3)] (H(2) = 1,7-bis(3-ethoxy-2
      hydroxyphenyl)- 2,6-diazahepta-1,6-diene) with Hg(NO(3))(2).H(2)O proceeds in an
      analogous manner with C-mercuration occurs para to the phenolic oxygen atom.

PMID- 20148208
TI  - Coordinatively polymeric and monomeric bismuth(III) complexes with pyridine
      carboxylic acids.
AB  - Three crystalline compounds, [Bi(2-O(2)C-C(5)H(4)N)(3)](n) (), {Bi[(2,6
      O(2)C)(2)C(5)H(3)N)][(2-HO(2)C-6-O(2)C)C(5)H(3)N].H(2)O}(n) (3) and
      Bi(O(2)CC(9)H(6)N)(2)(O(3)N)(O(2)CC(9)H(6)NH).2H(2)O () have been prepared by
      simple reactions in aqueous medium using the readily available bismuth nitrate
      and the corresponding acids, picolinic acid, dipicolinic acid and quinaldic acid.
      While and are coordination polymers with bismuth in tricapped trigonal prismatic
      and dodecahedral environments, compound is a monomeric species with dodecahedral
      geometry at bismuth. Compound represents a second crystalline form of a recently
      reported structure with subtle differences in bond parameters, and highlights the
      flexibility in structural motifs during crystallization. Compound involves
      skeletons with dimeric [Bi(2)O(2)] and trimeric [BiOCOBiOBiOCO] moieties. In ,
      while the N-protonated carboxylate forms a four-membered chelate ring with
      bismuth, the other two carboxylates form five-membered ring chelates with the
      nitrate accounting for the remaining two sites again as a chelate. TGA studies
      are consistent with the presence of non-coordinated water in and . Compounds and
      , although insoluble in most of the organic solvents and water, are readily
      soluble in dilute hydrochloric acid.

PMID- 20148210
TI  - Square structures and photophysical properties of Zn(2)Ln(2) complexes (Ln = Nd,
      Eu, Sm, Er, Yb).
AB  - Heterotetranuclear Zn(2)Ln(2) (Ln = Nd , Eu , Sm , Er , Yb ) complexes
      {Zn(2)(Mq)(2)(tpyO)(2)}{(Ln(hfac)(3))(2)} (HMq = 2-methyl-8-hydroxylquinoline,
      tpyOH = [2,2':6'2'']terpyridin-4'-ol, hfac = hexafluoroacetylacetonate) display
      novel square structures ligated by bifunctional ligands tpyO (mono- and
      tridentate) and Mq (chelating and bridging mu-phenoxo). These compounds exhibit
      sensitized lanthanide emission upon photo-excitation of ZnMq/tpy antenna
      chromophores. By virtue of the dual luminescence with complementary colors, the
      ZnMq/tpyO-based cyan emission and Sm(III)-centered orange luminescence are
      combined to generate a white-light emission in Zn(2)Sm(2) (4) complex.

PMID- 20148211
TI  - Neutral and zwitterionic half-sandwich Ir, Rh complexes supported by P,S
      substituted o-carboranyl ligands: Synthesis, characterization and reactivity.
AB  - The neutral Cp*M(Cl)(1-PPh(2)-2-S-1,2-C(2)B(10)H(10)) and zwitterionic Cp*M(3
      OCH(3)-7-PPh(2)-8-S-7,8-C(2)B(9)H(9)) (Cp* = eta(5)-C(5)Me(5), M = Ir, Rh, 1
      PPh(2)-2-S-1,2-C(2)B(10)H(10) = [1-(diphenylphosphino)-2-thiolato)-1,2-dicarba
      closo-carborane], 3-OCH(3)-7-PPh(2)-8-S-7,8-C(2)B(9)H(9) = [3-(methoxyl)-7
      (diphenylphosphino)-8-(thiolato)-7,8-dicarba-nido-carborane](-)) were synthesized
      and fully characterized. The 18-electron neutral closo-carborane complexes
      Cp*M(Cl)(1-PPh(2)-2-S-1,2-C(2)B(10)H(10)) (M = Ir (), Rh ()) can be easily
      deboronated to result in the formation of reactive 16-electron zwitterionic nido
      carborane complexes [Cp*M(3-OCH(3)-7-PPh(2)-8-S-7,8-C(2)B(9)H(9))] (M = Ir (),
      Rh()). The oxidation of with O(2) gas afforded the corresponding sulfone complex
      in high yields. Utilization of its unsaturated feature in 16-electron
      zwitterionic nido-carborane complexes offers a potential strategy to synthesize
      new types of organometallic complexes.

PMID- 20148212
TI  - Reactions of alkynes with phosphido niobocenes: a combined experimental and
      theoretical study.
AB  - The reactions of phosphido complexes [Nb(eta(5)-C(5)H(4)SiMe(3))(2)(L)(PPh(2))]
      [L = CO (1), CNxylyl (2), CNCy (3)] with alkynes have been carried out. The new
      diphenylphosphinoalkenyl niobocene complexes [Nb(eta(5)
      C(5)H(4)SiMe(3))(2)(eta(1)-C-C(CO(2)CH(3))=C(R)PPh(2))(CO)] [R = H (4), CH(3)
      (5)] and [Nb(eta(5)-C(5)H(4)SiMe(3))(2)(eta(1)-C-C(CO(2)R)=C(CO(2)R)PPh(2))(CO)]
      [R = CH(3), (6), R = (t)Bu, (7)] were successfully synthesized by the reaction of
      with methyl propiolate (HC[triple bond]CCO(2)CH(3)) or methyl 2-butynoate
      (CH(3)C[triple bond]CCO(2)CH(3)) and dimethyl 2-butynedioate [(CH(3)
      O(2)C)C[triple bond]C(CO(2)CH(3))] or di(tert-butyl) 2-butynedioate
      [((t)BuO(2)C)C[triple bond]C(CO(2)(t)Bu)], respectively. However, reaction was
      not observed with more electron-rich alkynes. Complex reacted with methyl
      propiolate, methyl 2-butynoate (MeC[triple bond]CCO(2)Me) or di(tert-butyl) 2
      butynedioate to give surprising new heteroniobacycle complexes [Nb(eta(5)
      C(5)H(4)SiMe(3))(2)(eta(1)-C-C(=NXylyl)C(R(1))=C(R(2))PPh(2)-kappa(1)-P)] [R(1) =
      H, R(2) = CO(2)Me (8); R(1) = Me, R(2) = CO(2)Me (9); R(1) = CO(2)(t)Bu, R(2) =
      CO(2)(t)Bu (10)]. Finally, the phosphido complexes and reacted with
      phenylacetylene (PhC[triple bond]CH) to give new diphenylphosphinoalkenyl
      niobocene derivatives [Nb(eta(5)-C(5)H(4)SiMe(3))(2)(eta(1)-C
      C(C(6)H(5))=C(H)PPh(2))(CNR)] [R = xylyl (11), Cy (12)]. All of these compounds
      were characterized by NMR spectroscopy and the molecular structure of was
      determined by single-crystal X-ray diffraction studies. Theoretical studies were
      also carried out by means of density functional theory (DFT) calculations on the
      insertions of alkynes into the Nb-P bond in the phosphido niobocenes.

PMID- 20148213
TI  - On the mechanism of carbonyl hydrogenation catalyzed by iron catalyst.
AB  - Density functional theory calculations have been performed to investigate the
      detailed mechanism of the carbonyl hydrogenation catalyzed by the first well
      defined bifunctional iron catalyst. The catalytic reaction proceeds by hydrogen
      transfer and dihydrogen activation. The hydrogen transfer reaction occurs via the
      bifunctional mechanism in which the two hydrogen atoms attached on the Fe and O
      of the catalyst are transferred to the oxygen and carbon atom of the carbonyl
      compound concertedly. Both the alcohol-mediated and nonalcohol-mediated
      dihydrogen activation processes are explored.

PMID- 20148214
TI  - Molecular, electronic structure and spectroscopic properties of MM quadruply
      bonded units supported by trans-6-carboethoxy-2-carboxylatoazulene ligands.
AB  - The reaction between M(2)(TiPB)(4) (M = Mo, W) where TiPB = 2,4,6
      triisopropylbenzoate and 6-carboethoxy-2-azulenecarboxylic acid (2 equiv.) in
      toluene leads to the formation of complexes M(2)(TiPB)(2)(6-carboethoxy-2
      azulenecarboxylate)(2). Compound (M = Mo) is blue and compound (M = W) is green.
      Both are air sensitive, hydrocarbon soluble species that gave the corresponding
      molecular ions in their mass spectra (MALDI-TOF). They show metal based
      oxidations and ligand based reductions. Electronic structure calculations (DFT
      and time dependent DFT) indicate that the two azulene carboxylate pi systems are
      coupled by their interactions with the M(2)delta orbitals. Their intense colors
      arise from M(2)delta to azulene pi* electronic transitions. While compound
      exhibits weak emission at approximately 900 nm, no emission has been detected for
      . Both and have been studied by fs and ns transient absorption spectroscopy. The
      X-ray analysis of the molecular structure of in the solid state confirmed the
      paddlewheel nature of its W(2)(O(2)C)(4) core and the trans orientation of the
      ligands.

PMID- 20148215
TI  - Solvothermal synthesis and magnetic properties of 3D flower-like NiHPO(3).H(2)O
      superstructures.
AB  - A self-assembled three-dimensional (3D) flower-like NiHPO(3).H(2)O
      micro/nanocomposite structure has been successfully synthesized for the first
      time by a simple solvothermal method, employing Na(6)P(6)O(18) as the phosphor
      source without the assistance of any template or surfactant. The as-obtained
      product was characterized by X-ray powder diffraction, scanning electron
      microscopy and transmission electron microscopy. The formation mechanism was
      proposed based on the evolution of this morphology as a function of solvothermal
      time. Some factors influencing the morphology of the NiHPO(3).H(2)O flower-like
      micro/nanocomposite structures were systematically investigated. The magnetic
      measurements demonstrated that the flower-like 3D superstructures exhibit
      ferromagnetic property.

PMID- 20148216
TI  - Excited state intramolecular proton transfer (ESIPT) in six-coordinated zinc(ii)
      quinoxaline complexes with ligand hydrogen bonds: their fluorescent properties
      sensitive to axial positions.
AB  - Zinc(ii)-quinoxaline complexes, [Zn(hqxc)(2)(py)(2)] and [Zn(hqxc)(2)(DMSO)(2)]
      (hqxc = 3-hydroxy-2-quinoxalinecarboxylate, py = pyridine, DMSO = dimethyl
      sulfoxide), were prepared and characterized by X-ray crystallography and
      fluorescence spectroscopy. In both complexes, the zinc ion is six-coordinated by
      two equatorial bidentate hqxc ligands with an intramolecular hydrogen bond and
      two axial monodentate ligands such as pyridine or DMSO. In spite of similar
      coordination geometries, there is a remarkable difference between their solid
      state fluorescent properties. The pyridine complex is strongly fluorescent
      (fluorescence quantum yield Phi = 0.22), giving rise to a significantly Stokes
      shifted spectrum. From its thin film photopumped by a nitrogen gas laser,
      amplified spontaneous emission was observed. These results suggest that the
      fluorescence occurs by way of excited-state intramolecular proton-transfer
      (ESIPT) in the hydrogen bond of hqxc. On the other hand, the DMSO complex shows
      fluorescent intensity (Phi = 0.08) lower than that of the pyridine complex, and
      shows normal emission in addition to ESIPT emission. From IR measurements for
      these complexes, it is concluded that axial ligands influence the hydrogen bond
      strength of the equatorial hqxc ligand via zinc and thus the ESIPT efficiency.

PMID- 20148217
TI  - Electronic structure of the members of the electron transfer series [NiL](z) (z =
      3+, 2+, 1+, 0) and [NiL(X)](n) (X = Cl, CO, P(OCH(3))(3)) species containing a
      tetradentate, redox-noninnocent, Schiff base macrocyclic ligand L: an
      experimental and density functional theoretical study.
AB  - The electronic structure of the four members of the electron transfer series
      [NiL](z) (z = 3+, 2+, 1+, 0) have been established experimentally (EPR
      spectroscopy and X-ray crystallography) and by density functional theoretical
      (DFT) calculations using the B3LYP functional in conjunction with a conductor
      like screening model (COSMO) for acetonitrile solvent effects. L represents a
      generic designation of the tetradentate macrocycle 2,12-dimethyl-3,7,11,17
      tetraazabicyclo[11.3.1]-heptadeca-1(17),2,11,13,15-pentane where the true
      oxidation level is not specified; (L(Ox))(0) represents its neutral form, (L )(1
      ) is the one-electron reduced pi radical anion, and (L(Red))(2-) is the singlet
      (or triplet) diradical dianion of this ligand. It is shown that the above series
      consists of square planar [Ni(III)(L(Ox))](3+) (S = 1/2), [Ni(II)(L(Ox))](2+) (S
      = 0), [Ni(II)(L )](1+) (S = 1/2), [Ni(II)(L(Red))](0) (S = 0). The structure of
      [Ni(II)(L(Red))](0) has been determined by X-ray crystallography. The
      electrochemistry of [Ni(II)(L(Ox))](PF(6))(2) in the presence of hard chloride
      anions shows the presence of trans-[Ni(III)(L(Ox))Cl(2)](+), the EPR spectrum of
      which has been recorded and calculated, and of trans-[Ni(II)(L(Ox))Cl(2)](0) (S =
      1). Upon further reduction the coordinated Cl(-) ligands dissociate and [Ni(II)(L
      )](1+) and [Ni(II)(L(Red))](0) are successively generated. Similarly, in the
      presence of good pi-acceptor ligands such as CO or P(OCH(3))(3) the following
      five-coordinate, square base pyramidal species are found to be stable:
      [Ni(I)(L(Ox))(X)](1+) (S = 1/2), [Ni(I)(L )(X)](0) (S = 0, 1) (X = CO,
      P(OCH(3))(3)). As shown by EPR spectroscopy in the work of J. Lewis and M.
      Schroder, J. Chem. Soc., Dalton Trans., 1982, 1085, the monocations consist of a
      central nickel(i) ion (d(9), S(Ni) = 1/2). These spectra have been faithfully
      reproduced by the calculations. The neutral complexes [Ni(I)(L )(X)](0) are
      singlet or triplet diradicals comprising a central nickel(i) ion and a pi radical
      anion (L )(1-). Interestingly, six-coordinate species trans-[Ni(L)(X)(2)](n) (n =
      2+, 1+, 0) are computationally not stable in the gas phase or in solution. No
      experimental evidence has been found for their existence.

PMID- 20148218
TI  - Hydrogen bonding to carbonyl hydride complex Cp*Mo(PMe(3))(2)(CO)H and its role
      in proton transfer.
AB  - The interaction of the carbonyl hydride complex Cp*Mo(PMe(3))(2)(CO)H with
      Bronsted (fluorinated alcohols, (CF(3))(n)CH(3-n)OH (n = 1-3), and CF(3)COOH) and
      Lewis (Hg(C(6)F(5))(2), BF(3).OEt(2)) acids was studied by variable temperature
      IR and NMR ((1)H, (31)P, (13)C) spectroscopies in combination with DFT/B3LYP
      calculations. Among the two functionalities potentially capable of the
      interaction - carbonyl and hydride ligands - the first was found to be the
      preferential binding site for weak acids, yielding CO...HOR or CO...Hg complexes
      as well as CO...(HOR)(2) adducts. For stronger proton donors ((CF(3))(3)COH,
      CF(3)COOH) hydrogen-bonding to the hydride ligand can be revealed as an
      intermediate of the proton transfer reaction. Whereas proton transfer to the CO
      ligand is not feasible, protonation of the hydride ligand yields an (eta(2)-H(2))
      complex. Above 230 K dihydrogen evolution is observed leading to decomposition.
      Among the decomposition products compound
      [Cp*Mo(PMe(3))(3)(CO)](+)[(CF(3))(3)CO.2HOC(CF(3))(3)](-) resulting from a
      phosphine transfer reaction was characterized by X-ray diffraction. Reaction with
      BF(3).OEt(2) was found to produce [Cp*Mo(PMe(3))(2)(CO)BF(4)] via initial attack
      of the hydride ligand.

PMID- 20148219
TI  - Reactions of germenes with various naphthoquinones controlled by substituent
      effects.
AB  - The germene Mes(2)Ge=CR(2) (Mes = 2,4,6-trimethylphenyl, CR(2) = fluorenylidene)
      reacts with 5-methoxy-1,4-naphthoquinone to yield, via the o-quinodimethane , the
      endoperoxyde by simple reaction with molecular oxygen. By contrast, with 2,3
      dichloro-1,4-naphthoquinone gives the tetracyclic compound by a double [2 + 4]
      cycloaddition between the Ge=C double bond and the conjugated system O=C-CH=CH.
      The new steric demanding germene Mes(2)Ge=CR'(2) (CR'(2) = 2,7-di-tert
      butylfluorenylidene) undergoes similar [2 + 4] cycloadditions with various
      substituted or unsubstituted naphthoquinones, leading to tetracyclic adducts .
      The germene , the endoperoxide and the cycloadducts and have been structurally
      characterized.

PMID- 20148220
TI  - Relativistic ab initio study on PtF and HePtF.
AB  - The electronic structures and spectroscopic constants of the first three low
      lying electronic states (Omega = 1/2, 3/2, and 5/2) of the linear HePtF complex
      were investigated by highly accurate relativistic ab initio methods, in which the
      spin-orbit coupling was taken into account, and compared with the results of PtF.
      It shows that the complex is significantly different from the typical van der
      Waals systems because of short He-Pt bond distances (1.80 approximately 1.87 A),
      large He-Pt stretching frequencies (500 approximately 600 cm(-1)), considerable
      binding energies (1400 approximately 2500 cm(-1) with corrections), and a small
      electron transfer from helium (about 0.06). However, the topological analysis of
      the electron density distribution indicates that there is strong van der Waals
      interaction in the He-Pt bond instead of weak covalent one.

PMID- 20148221
TI  - DNA photonuclease activity of four new copper(II) complexes under UV and red
      light: theoretical/experimental correlations with active species generation.
AB  - In this study, four new mononuclear copper(ii) complexes, [Cu(L(1))(dpq)]ClO(4)
      (), [Cu(L(1))(phen)]ClO(4) (), [Cu(L(2))(dpq)]ClO(4) (), [Cu(L(1))(OAc)] (), and
      the known complex [Cu(dpq)(2)(H(2)O)]ClO(4) (), were synthesized and
      characterized by various methods (dpq = dipyrido[3,2-d:2',3'-h]quinoxaline, L(1)
      = (3,5-di-tert-butyl-2-hydroxybenzyl)(2-pyridylmethyl)imine, L(2) = (2
      hydroxybenzyl)(2-pyridylmethyl)imine). The structure of [Cu(L(1))(dpq)]ClO(4) ()
      was determined by X-ray crystallography and reveals that the Cu(II) center is
      coordinated by dpq and by the N(2)O donor ligand L(1) in a distorted square
      pyramidal arrangement. The interaction of with calf thymus DNA was measured and
      the binding constant K(b) was obtained for the complexes, with values strongly
      dependent on the intercalating and/or binding properties of the ligands present
      in the structure of each complex. Also, the nuclease and photonuclease activity
      in terms of plasmid DNA cleavage with addition of reactants was monitored, in
      order to verify the mechanism through which the complexes cleave DNA. The
      complexes displayed good activity under both UV (365 nm) and red light (635 nm)
      irradiation, with the Type II mechanism prevailing in the case of the former and
      Type I mechanism for the latter. Finally, two new correlations between the
      experimental and theoretical parameters are discussed and some hypotheses
      regarding the active species generation are proposed.

PMID- 20148222
TI  - A theoretical study of X ligand effect on catalytic activity of complexes
      RuHX(diamine)(PPh(3))(2) (X = NCMe, CO, Cl, OMe, OPh, CCMe and H) in H(2)
      hydrogenation of ketones.
AB  - In this paper, the catalytic activities of RuHX(diamine)(PPh(3))(2) complexes
      with different X ligands (X = NCMe, CO, Cl, OMe, OPh, CCMe and H, corresponding
      catalytic processes are abbreviated in A, B, C, D, E, F and G systems,
      respectively) in the H(2)-hydrogenation of ketones were investigated using
      density functional theory (DFT) method. Calculated results indicate that the rate
      determining step in the whole catalytic cycle is hydrogen transfer (HT) for A-E
      but dihydrogen activation (DA) for F and G. The free energy barriers of the HT
      step for A-G are 36.1, 32.3, 21.2, 14.9, 21.9, 9.4 and 6.9 kcal mol(-1),
      respectively. The DA step consists of hydrogen coordination (HC) and hydrogen
      splitting (HS) steps if dihydrogen coordinates with the Ru center. The transition
      states (TSs) of H(2) coordinating with the Ru atom for A-G except B are located.
      The free energy barriers of DA for A-G are 17.8 (17.8, 2.6), 21.5, 12.8 (12.8,
      3.8), 12.2 (11.2, 6.2), 13.6 (13.6, 4.1), 17.1 (9.7, 7.5) and 22.0 (10.4, 11.0)
      kcal mol(-1), respectively (the data in parentheses correspond to the barriers of
      HC and HS). HT barriers correlate well with the charges of hydride (H) in complex
      . HC barriers are closely related to the Ru[double bond, length as m-dash]N(1)
      double bond in , and HS are in line with the proton-moved-distances (PMDs) from
      to . This study demonstrates that catalysts D, F and G show better catalytic
      activities than the others, which is in good agreement with experimental results.

PMID- 20148223
TI  - A new calcium sulfate hemi-hydrate.
AB  - Calcium sulfate hydrates receive significant attention due to numerous large
      scale industrial applications. There has been a long debate on the possible
      existence of two gypsum hemi-hydrate polymorphs, denoted alpha- and beta
      CaSO(4).0.5H(2)O. In this work, a new crystal structure of calcium sulfate hemi
      hydrates is presented, denoted beta-CaSO(4).0.5H(2)O. The structure was solved
      using powder neutron diffraction data, the space group is P3(1) and the unit cell
      in a hexagonal setting a = 6.9268(1), c = 12.7565(3) A. The structure has two
      calcium-oxygen coordination polyhedra: Ca1 is eight coordinated and has Ca-O bond
      lengths in the range 2.31(3) to 2.89(2) A and Ca2 is nine coordinated and has one
      Ca-O(water) bond length of 2.43(3) A, and eight Ca-O bonds in the range 2.30(4)
      to 2.86(4) A. Two sulfate ions have S-O bonds in the range 1.47(3) to 1.49(4) A,
      and 1.47(3) to 1.50(3) A, respectively. The water molecule forms a hydrogen bond
      of 2.55(4) A to an oxygen atom in one of the sulfate ions. The structure of the
      hemi-hydrate beta-CaSO(4).0.5H(2)O has one-dimensional channels running parallel
      to the c-axis where the water molecules are located. This relates the structures
      of alpha- and beta-CaSO(4).0.5H(2)O and soluble anhydrite AIII-CaSO(4), which all
      have similar channel structures. The water molecules in the structure of beta
      CaSO(4).0.5H(2)O are packed in the channels with a three fold (3(1)) symmetry in
      a different way as compared to the pseudo hexagonal found in the structure of
      alpha-CaSO(4).0.5H(2)O.

PMID- 20148224
TI  - Studies on an iron(iii)-peroxo porphyrin. Iron(III)-peroxo or iron(II)-superoxo?
AB  - We demonstrate that a one electron reduced product of the heme iron dioxygen
      adduct exists in solution not only as the commonly accepted iron(iii)-peroxo
      species, but coexists with its isomeric iron(ii)-superoxo form. This unusual
      reduced metal-superoxide adduct [M(ii)-O(2)(-)] is recently reported as a
      reactive intermediate in the case of non-heme extradiol dioxygenases and could
      also be generated by cryoreduction of a heme Fe(II)-O(2) adduct. The existence of
      iron(ii)-superoxo species in solution is consistent with IR, EPR, mass and
      Mossbauer spectra. The equilibrium between heme iron(iii)-peroxo and iron(ii)
      superoxo forms is supported by density functional theory and explains our
      previous finding that upon release of coordinated (su)peroxide a corresponding
      iron(ii) complex remains. These results shed new light on the nature of heme
      iron(iii)-peroxo species that are key intermediates in the metalloenzyme
      catalyzed dioxygen and hydrogen peroxide activation.

PMID- 20148225
TI  - Synthesis and electrochemistry of some ferrocenyl substituted dicarba- and
      tricarbaborane compounds.
AB  - Treatment of arachno-4-Me(2)S-B(9)H(13) (1) with ethynylferrocene, FcC[triple
      bond]CH (Fc = ferrocenyl), in boiling benzene afforded an inseparable 2 : 1
      mixture of 6-Fc-nido-5,6-C(2)B(8)H(11) (2a) and 5-Fc-nido-5,6-C(2)B(8)H(11) (2b)
      in a 10% yield. However, compound 2b was converted quantitatively to the pure,
      violet 2a by the action of proton sponge (PS), followed by acidification. The
      structure of 2a was determined by X-ray diffraction analysis. Heating of 2a at
      400 degrees C led to the dehydrogenation and isolation of the orange 1-Fc-closo
      1,10-C(2)B(8)H(9) (3) in almost quantitative yield, while treatment of 2a with t
      BuNC and PS (proton sponge = 1,8-bis(dimethylamino)naphthalene) in CH(2)Cl(2)
      generated the neutral absolute tautomer 7-t-BuNH-8-Fc-7,8,9-C(3)B(8)H(10) (N4)
      (yield 50%), which could be converted quantitatively into the zwitterionic
      tautomer 7-t-BuNH(2)-8-Fc-7,8,9-C(3)B(8)H(9) (Z4) via dissolution in MeCN.
      Tautomers N4 and Z4 sharply differ in NMR properties and both gave rise to a pair
      of cage-isomeric closo ferratricarbollides, [1-Cp-2-Fc-12-t-BuNH-1,2,4,12
      FeC(3)B(8)H(9)] (5a) (Cp = eta(5)-C(5)H(5)) (yield 48%) and [1-Cp-2-Fc-10-t-BuNH
      1,2,4,10-FeC(3)B(8)H(9)] (5b) (yield 32%), upon heating with [CpFe(CO)(2)](2) in
      mesitylene at reflux. Electrochemical studies revealed that the compounds display
      one (compounds 2a and 3) or two (compounds 5a and 5b) well-defined, reversible
      one-electron Fe(II)/Fe(III) redox changes.

PMID- 20148226
TI  - The competition between Si-Si and Si-C cleavage in functionalised oligosilanes:
      their reactivity with elemental lithium.
AB  - The reaction of aryl-substituted disilanes with elemental lithium is a common
      method for the preparation of lithiosilanes and the subsequent synthesis of
      functionalised oligosilanes, especially of enantiomerically pure compounds. A
      series of alkyl- and arylsubstituted di- and trisilanes has been investigated
      with respect to their reactivity against elemental lithium. Thereby, depending on
      the substituents, silicon-silicon bond cleavage of the central Si-Si unit and/or
      silicon-carbon bond cleavage to arenes are observed. Quantum chemical studies
      provide a deeper insight into the ongoing processes. The reactive centre can be
      estimated by both, bond elongation after electron transfer and frontier orbital
      interactions (pi-bonding and sigma-antibonding part). Aromatic substituents at
      the silicon atoms proved to be necessary for the processing of any cleavage
      reaction in the studied systems by stabilising the radical anion after electron
      transfer at the corresponding di- or trisilane. Yet, selective cleavage reactions
      do not depend on the number of arenes.

PMID- 20148227
TI  - Modulation of the luminescence quantum efficiency for blue luminophor
      {Al(salophen)}(+) by ester-substituents.
AB  - A series of Al(III) complexes of a salophen (N,N'-bis(salicylidene)-o
      phenylenediamine) derivative with an ester substituent at the C5 position of the
      salicylidene rings have been prepared and their luminescence properties
      investigated. All exhibit a bright blue emission (lambda(em) = 478 nm) that is
      observed neither for other metal ions nor with the non-functionalized ligand.
      Moreover, the ester-R group (Me, (t)Bu, Ph) was found to significantly affect the
      quantum yields (varphi = 12 to 20%) of the luminophor. DFT calculations have been
      undertaken to reveal the influence of the ester and its R-group on the frontier
      molecular orbitals. Preparation and photoluminescence properties in solution and
      solid state are reported. The crystal structure of a pyridine oxide adduct
      [L(tBu)Al(PyO)(2)].NO(3), where L(tBu) stands for the tButyl-ester functionalized
      Schiff base, has been solved.

PMID- 20148228
TI  - Cucurbit[10]uril binding of dinuclear platinum(II) and ruthenium(II) complexes:
      association/dissociation rates from seconds to hours.
AB  - A simpler method for the purification of cucurbit[10]uril (Q[10]) from the
      Q[10].Q[5] inclusion complex is reported. 1,12-Diaminododecane was used to
      displace Q[5], as opposed to the synthetic melamine derivative currently used.
      The binding of trans-[{PtCl(NH(3))(2)}(2)(micro-NH(2)(CH(2))(8)NH(2))](2+)
      (CT008) and [{Ru(phen)(2)}(2)(micro-bb(5))](4+) {phen = 1,10-phenanthroline;
      bb(5) = 1,5-bis[4(4'-methyl-2,2'-bipyridyl)]pentane} (Rubb(5)) to Q[10] was
      studied by (1)H NMR and luminescence spectroscopy, cyclic voltammetry and
      molecular modelling. The (1)H NMR resonances of the methylene protons in the
      bridging ligands of CT008 and Rubb(5) exhibited large upfield chemical shift
      changes upon addition of Q[10]. These shifts are indicative of encapsulation of
      the bridging ligand within the Q[10] cavity, with the metal centres positioned
      outside the portals. (1)H NMR-based kinetics experiments with Rubb(5) show the
      presence of a portal-bound intermediate which progresses to a completely
      encapsulated inclusion complex only after many hours. The large metal centres of
      Rubb(5) provide a restriction to the movement of the complex in and out of the
      cavity and result in binding kinetics that are slow on both the (1)H NMR and
      biological timescales. This result was consistent with molecular modelling
      simulations. Cyclic voltammetry showed that the Ru(III/II) couple of free Rubb(5)
      appeared at +1.058 V (vs Ag/AgCl), with the first ligand reduction observed as a
      shoulder ( approximately -1.38 V) on the edge of the solvent (water) front. The
      Q[10]-bound complex exhibited an anodic shift of 48 mV compared to the free metal
      complex. Luminescence spectroscopy of the binding of Rubb(5) to Q[10] yielded an
      approximate binding constant of 1.9 x 10(9) M(-1). Although CT008 was
      encapsulated within Q[10], the inclusion complex was not soluble in several
      buffers at pH 7.0. These results indicate that Q[10] is not an effective delivery
      vehicle for dinuclear platinum(II) anti-cancer drugs; however, due to the strong
      binding affinity and slow exchange rates, Q[10] does show considerable promise as
      a delivery mechanism for controlled slow release of large dinuclear ruthenium(II)
      complexes.

PMID- 20148230
TI  - Stereoselectivity induced by support confinement effects. Aza-pyridinoxazolines:
      A new family of C(1)-symmetric ligands for copper-catalyzed enantioselective
      cyclopropanation reactions.
AB  - Aza-pyridinoxazoline ligands, a new class of C(1)-symmetric ligands, are
      described and tested in the heterogeneous enantioselective catalysis of a
      cyclopropanation reaction, with the aim of improving surface confinement effects
      by the clay support on the reaction stereoselectivity. In the case of trans/cis
      diastereoselectivity, these surface effects lead to a systematic reversal of
      selectivity, cis-cyclopropanes being favored. Regarding the enantioselectivities,
      support confinement has a positive effect in the case of major cis-cyclopropane
      products, leading to moderate enantioselectivity values (60% ee). A theoretical
      (DFT) mechanistic study is carried out to explain the origin of the
      enantioselectivity in the homogeneous phase at a molecular level, and to get
      insights on the geometries of the key intermediates and transition structures.

PMID- 20148229
TI  - Biimidazole containing cobalt(III) mixed ligand complexes: Crystal structure and
      photonuclease activity.
AB  - Two new mixed ligand complexes of cobalt(iii) containing ancillary biimidazole
      ligands, [Co(phen)(2)H(2)biim](ClO(4))(3).0.5(H(7)O(3))(ClO(4)) (1) and
      [Co(bpy)(2)H(2)biim](ClO(4))(3).3H(2)O (2) have been synthesized and
      characterized by various spectroscopic and electrochemical techniques. Both
      complexes and , have been characterized by the single crystal X-ray diffraction
      method. While cobalt complex was found to crystallize in the triclinic system
      with the P1[combining macron] space group, complex was found to crystallize in
      the orthorhombic system with the Pbca space group. The unit cell packing of
      complex shows the presence of a water cluster, which is buttressed by oxygen
      atoms present in the perchlorate anions and water with an average OO bond
      distance of 2.41-2.86 A. Interaction of these complexes with calf thymus DNA (CT
      DNA) was investigated by electronic spectral titrations. The results suggest that
      complexes and bind to DNA through the groove via hydrogen bonding. This is due to
      the presence of -NH in the ancillary ligand biimidazole, which favors hydrogen
      bonding with DNA base pairs. The intrinsic DNA binding constant values for
      complexes and were found to be (5.18 +/-0.23) x 10(4) M(-1) and (1.26 +/- 0.13) x
      10(4) M(-1) respectively. Groove binding of these complexes with DNA is further
      supported by viscosity measurements, thermal denaturation and circular dichroism
      studies. Among the two cobalt complexes, complex possesses greater DNA binding
      strength due to the presence of the conjugated aromatic structure of the phen
      ligand which increases the hydrophobic interactions with DNA. DNA cleavage
      experiments using plasmid DNA pUC 18 show that these complexes exhibit efficient
      photonuclease activity in the presence of molecular oxygen.

PMID- 20148231
TI  - Coordination networks constructed with the multinuclear silver-ethynide
      supramolecular synthon 4-nitrophenyl-C[triple bond]C subset Ag(n) (n = 3, 4, 5).
AB  - A series of thirteen new silver(I) double and multiple salts containing 4
      nitrophenylethynide (L), namely AgL.4AgCF3COO.CH3CN (1), AgL.5AgCF3COO.3CH3CN
      (2), 3AgL.4AgCF3COO.2CH3CN (3),3AgL.7AgCF3COO.6CH3CN (4), AgL.3AgC2F5COO.CH3CN
      (5), 4AgL.4AgC3F7COO.3CH3CN (6),2AgL.4AgCF3COO.NC(CH2)2CN (7),
      AgL.3AgCF3COO.CH3CN.0.5NC(CH2)4CN (8),AgL.3AgC2F5COO.CH3CN.NC(CH2)4CN (9),
      4AgL.12AgCF3COO.4(m-NCC6H4CN).H2O (10), AgL.2[CF2(CF2COOAg)2].4.5H2O (11),
      AgL.CF2(CF2COOAg)2.AgCF3COO.H2O (12) and AgL.CF2(CF2COOAg)2.AgC2F5COO.H2O (13),
      have been synthesized and characterized by X-raycrystallography. All these
      compounds contain the multinuclear silver-ethynide supramolecular synthonR
      C[triple bond]C subset Agn (R = 4-nitrophenyl; n = 3, 4, 5). High-dimensional
      metal-organic frameworks areachieved in these complexes via the linkage of
      characteristic carboxylate-bridged infinite silver chainsby nitro-silver
      coordination or weak interactions. In addition, the nitrophenyl group exhibits
      itsversatile ability to form other intermolecular interactions such as
      nitro...nitro, pi...pi, and C-H...O hydrogen bonding to stabilize the network
      structure. Furthermore, several factors affecting thesupramolecular
      architectures, including the incorporation of nitriles and/or
      bidentateperfluorocarboxylates as co-existing ligands are also discussed.

PMID- 20148232
TI  - Novel embedded Pd@CeO(2) catalysts: a way to active and stable catalysts.
AB  - 1-wt% Pd-CeO(2) catalysts were prepared by co-precipitation of Pd nanoparticles
      with ceria (Pd@CeO(2)-CP), by a microemulsion procedure (Pd@CeO(2)-ME), and by
      normal impregnation of Pd salts (Pd/CeO(2)-IMP) in order to test the concept that
      Pd-CeO(2) catalysts could be more stable for the water-gas-shift (WGS) reaction
      when the Pd is embedded in CeO(2). Initial WGS rates measured at 250 degrees C
      were similar for the Pd@CeO(2)-CP and Pd/CeO(2)-IMP, indicating that Pd was
      accessible for gas-phase reactions on both catalysts. Pd@CeO(2)-CP exhibited
      better stability for WGS than did Pd/CeO(2)-IMP but exposure to the WGS
      environment at 400 degrees C still caused a decrease in activity. Physical
      characterization of the Pd@CeO(2)-ME implied that the core-shell nanoparticles
      underwent condensation that resulted in a low surface area and poor Pd
      accessibility. However, the Pd@CeO(2)-ME sample exhibited good stability for WGS,
      suggesting that more effective encapsulation of Pd can limit the sintering of the
      metal phase, thus resulting in stable catalysts under high temperature reaction
      conditions.

PMID- 20148233
TI  - An effective approach to artificial nucleases using copper(II) complexes bearing
      nucleobases.
AB  - Novel copper(ii) complexes bearing 2,2'-bipyridine (bpy) derivatives with
      adenine, thymine and uracil nucleobases [Cu(L(1))Cl(2)].2H(2)O (1),
      [Cu(L(2))Cl(2)] (2) and [Cu(L(3))Cl(2)].H(2)O (3) (L(1) = 5,5'-Di[N9
      adenylmethyl]-2,2'-bipyridine, L(2) = 5,5'-Di[N1-thyminylmethyl]-2,2'-bipyridine
      and L(3) = 5,5'-Di[N1-uracilmethyl]-2,2'-bipyridine) were synthesized and
      characterized. Structure simulation was performed for these complexes. Circular
      dichroism (CD) spectra revealed the interactions between these ligands and pBR322
      DNA and showed that the local DNA structure was perturbed by these ligands.
      Cleavage of pBR322 DNA by these complexes was carried out in 20 mM HEPES (pH 7.5)
      at 37 degrees C. The calculated pseudo-Michaelis-Menten kinetic parameters
      (k(cat)) were 14.7 +/- 0.6 and 40.4 +/- 1.3 h(-1) for and . The cleavage
      efficiency of was 80-fold higher than that of its simple analogue [Cu(bpy)Cl(2)]
      (k(cat) = 0.50 h(-1)) and very close to the catalytic rate constant of natural
      EcoRI endonuclease (k(cat) = 43.2 h(-1)) at similar conditions. Thus, complex
      might be one of the most effective artificial nucleases that could catalyze
      double-stranded DNA hydrolytic cleavage so far. Hydrolytic mechanisms involved in
      DNA cleavage were explored using radical scavengers and T4 ligase. Competitive
      experiments with special binding agents showed that complexes could
      preferentially bind to the minor groove of double-stranded DNA, suggesting
      specific DNA binding characteristics. Molecular docking calculations also
      indicated that complexes could bind to the minor groove of targeted DNA much more
      strongly than their simple analogues and preferentially bind at the AT region of
      the dodecamer. Such high DNA cleavage ability and selectivity of these copper(ii)
      complexes could be attributed to the synergic effects of the metal center and the
      pendant nucleobases.

PMID- 20148234
TI  - Molecular tectonics: formation and structural studies on a 2-D directional
      coordination network based on a non-centric metacyclophane based tecton and zinc
      cation.
AB  - The combination of tectons based on the [1111]metacyclophane backbone blocked the
      1,3-alternate conformation bearing two imidazoly or pyrazolyl groups located on
      the same side with metal halide complexes leads to the formation of either
      discrete metallmacrobicycles or infinite 1-D coordination networks. The same
      backbone bearing two sets of two different coordinating poles composed of two
      pyridyl and two pyrazolyl units, owing to its non-centrosymmetric nature, forms a
      directional 2-D network packed in an anti-parallel fashion.

PMID- 20148235
TI  - Oxovanadium(IV) complexes of phenanthroline bases: the dipyridophenazine complex
      as a near-IR photocytotoxic agent.
AB  - Oxovanadium(iv) complexes [VOCl(B)(2)]Cl (1-3) of phenanthroline bases (B), viz.
      1,10-phenanthroline (phen in ), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in ) and
      dipyrido[3,2-a:2',3'-c]phenazine (dppz in ), have been prepared, characterized
      and their DNA and protein binding, photo-induced DNA and protein cleavage
      activity and photocytotoxicity have been studied. Complex , structurally
      characterized by X-ray crystallography, shows the presence of a vanadyl group in
      VOClN(4) coordination geometry. The dpq ligand displays a chelating mode of
      binding with a N-donor site trans to the oxo-group. The chloride ligand is cis to
      the oxo-group. The one-electron paramagnetic complexes show a d-d band near 715
      nm in 15% DMF-Tris-HCl buffer. The complexes are redox active exhibiting a
      V(iv)/V(iii) redox couple within -0.5 to -0.7 V vs. SCE in 20% DMF-Tris-HCl/0.1 M
      KCl. The complexes bind to calf thymus (CT) DNA in the order: (dppz) > (dpq) >
      (phen). The binding data reveal the groove and/or partial intercalative DNA
      binding nature of the complexes. The complexes show "chemical nuclease" activity
      in the dark in the presence of 3-mercaptopropionic acid or hydrogen peroxide via
      a hydroxyl radical pathway. The dpq and dppz complexes are efficient
      photocleavers of DNA in UV-A light of 365 nm forming reactive singlet oxygen
      ((1)O(2)) and hydroxyl radical ( OH) species. Complexes and also show DNA
      cleavage activity in red light (>750 nm) by an exclusive OH pathway. The
      complexes display a binding propensity to bovine serum albumin (BSA) protein
      giving K(BSA) values in the range of 7.1 x 10(4)-1.8 x 10(5) M(-1). The dppz
      complex shows BSA and lysozyme protein cleavage activity in UV-A light of 365 nm
      via OH pathway. The dppz complex exhibits significant PDT effect in human
      cervical cancer HeLa cells giving IC(50) values of 1.0 microM and 12.0 microM in
      UV-A and visible light, respectively (IC(50) = >100 microM in the dark).

PMID- 20148237
TI  - Comparison between classic Gibson and Cooke technique and sweat conductivity test
      in patients with and without cystic fibrosis.
AB  - OBJECTIVE: To compare sweat chloride values obtained by quantitative pilocarpine
      iontophoresis (classic test) with the sweat conductivity values obtained using
      Macroduct collection system in patients with and without cystic fibrosis (CF).
      The cost and time spent to carry out each test were also analyzed. METHODS: The
      sweat test using both techniques was performed at the same time in patients with
      and without CF. Conductivity cutoff values to rule out or diagnose CF were < 75
      and > or = 90 mmol/L, respectively, and for the classic test the chloride values
      were < 60 and > or = 60 mmol/L. RESULTS: Fifty-two patients with CF (29 males and
      23 females; aged from 1.5 to 18.2 years) underwent the sweat test using both
      techniques, showing median sweat chloride and conductivity values of 114 and 122
      mmol/L, respectively. In all of them, conductivity was > or = 95 mmol/L, which
      provided the test with 100% sensitivity (95%CI 93.1-100). Fifty patients without
      CF (24 males and 26 females; aged from 0.5 to 12.5 years) had median sweat
      chloride and conductivity values of 15.5 and 30 mmol/L, respectively. In all
      cases, conductivity was < 70 mmol/L, which provided the test with 100%
      specificity (95%CI 92.9-100). Time spent to perform the tests was significantly
      shorter for the conductivity test, and its cost was also lower. CONCLUSIONS: The
      conductivity test showed high sensitivity and specificity, and there was good
      correspondence between the tests. The time spent to carry out the conductivity
      test was shorter and the cost was lower in comparison with the classic test.

PMID- 20148238
TI  - [Therapy management of chylothorax].
AB  - The diagnosis and treatment of chylothorax poses a challenge to the surgeons'
      daily practice. The leakage of chyle into the thoracic cavity leads to
      hypovolemia and also to dysfunction of lipid metabolism, electrolyte imbalance,
      avitaminosis and immunosuppression. If untreated, the disease will have fatal
      consequences. This article gives a detailed review of the anatomy, physiology,
      pathophysiology, diagnostics and treatment options in the management of
      chylothorax.

PMID- 20148239
TI  - Modifier genes in pseudoxanthoma elasticum: novel insights from the Ggcx mouse
      model.

PMID- 20148240
TI  - [Post-traumatic torticollis in a schoolchild: fracture, congenital anomaly or age
      appropriate radiological findings of the atlas?].
AB  - We describe the case of a 6-year-old girl with post-traumatic torticollis after
      falling on her head. The suspected fractures of the dens axis and/or atlas were
      ruled out after performing CT and MRI examinations as well as dynamic
      fluoroscopy. Radiological findings showed no further instability but there was a
      congenital non-fusion of the posterior arch and an age-appropriate non-fused
      anterior arch of the atlas. In addition to discoligamental injuries and
      fractures, congenital anomalies and normal variants of the immature anatomy of
      the cervical spine should also be considered in the diagnosis of the pediatric
      cervical spine after trauma.

PMID- 20148241
TI  - Validation of the Prolapse Quality of Life (P-QOL) questionnaire in Thai version.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to validate the Thai
      version of the Prolapse Quality of Life (P-QOL) questionnaire. METHODS: The P-QOL
      questionnaire was translated into Thai. Test-retest reliability and internal
      consistency were tested. All patients who visit the gynecologic outpatient clinic
      of King Chulalongkorn Memorial Hospital between March 2008 and September 2009
      completed the P-QOL questionnaires. RESULTS: One hundred fifteen patients with
      symptomatic pelvic organ prolapse and 60 asymptomatic patients were included.
      There was a significant correlation between P-QOL domain scores and vaginal
      examination findings (POP-Q stage). A higher POP-Q stage and a higher impact on
      quality of life were detected in symptomatic patients. The total scores from all
      domains were significantly higher in symptomatic patients. CONCLUSION: The Thai
      version of the P-QOL questionnaire is a valid, reliable, and simple instrument to
      assess the symptoms' severity and the quality of life in Thai-speaking patients
      with pelvic organ prolapse.

PMID- 20148242
TI  - Quantification of chlorpheniramine maleate enantiomers by ultraviolet
      spectroscopy and chemometric methods.
AB  - Chlorpheniramine maleate (CLOR) enantiomers were quantified by ultraviolet
      spectroscopy and partial least squares regression. The CLOR enantiomers were
      prepared as inclusion complexes with beta-cyclodextrin and 1-butanol with mole
      fractions in the range from 50 to 100%. For the multivariate calibration the
      outliers were detected and excluded and variable selection was performed by
      interval partial least squares and a genetic algorithm. Figures of merit showed
      results for accuracy of 3.63 and 2.83% (S)-CLOR for root mean square errors of
      calibration and prediction, respectively. The ellipse confidence region included
      the point for the intercept and the slope of 1 and 0, respectively. Precision and
      analytical sensitivity were 0.57 and 0.50% (S)-CLOR, respectively. The
      sensitivity, selectivity, adjustment, and signal-to-noise ratio were also
      determined. The model was validated by a paired t test with the results obtained
      by high-performance liquid chromatography proposed by the European pharmacopoeia
      and circular dichroism spectroscopy. The results showed there was no significant
      difference between the methods at the 95% confidence level, indicating that the
      proposed method can be used as an alternative to standard procedures for chiral
      analysis.

PMID- 20148243
TI  - Doping control analysis of recombinant human erythropoietin, darbepoetin alfa and
      methoxy polyethylene glycol-epoetin beta in equine plasma by nano-liquid
      chromatography-tandem mass spectrometry.
AB  - Recombinant human erythropoietin (rhEPO), darbepoetin alfa (DPO) and methoxy
      polyethylene glycol-epoetin beta (PEG-EPO) are synthetic analogues of the
      endogenous hormone erythropoietin (EPO). These erythropoiesis-stimulating agents
      have the ability to stimulate the production of red blood cells and are
      commercially available for the treatment of anaemia in humans. These drugs are
      understood to have performance-enhancing effects on human athletes due to their
      stimulation of red blood cell production, thereby improving delivery of oxygen to
      the muscle tissues. Although their effect on horses has not been proven, these
      substances were thought to be similarly performance enhancing and have indeed
      been applied covertly to horses. As such, these protein-based drugs are
      prohibited by authorities in both human and equine sports. The method officially
      adopted by the International Olympic Committee (IOC) and World Anti Doping Agency
      (WADA) for the confirmation of rhEPO and/or DPO (rhEPO/DPO) in human urine is
      based on electrophoresis in combination with Western blotting. A shortcoming of
      the WADA method is the lack of definitive mass spectral data for the confirmation
      of a positive finding. Recently, a liquid chromatography-tandem mass spectrometry
      (LC/MS/MS) method for the detection and confirmation of rhEPO/DPO in equine
      plasma was reported. However, we have not been successful in achieving the
      reported sensitivity. This paper presents a method for the detection and
      confirmation of rhEPO/DPO, as well as the newly released PEG-EPO, in equine
      plasma. The procedures involve immunoaffinity extraction using anti-rhEPO
      antibody-coated Dynabeads followed by trypsin digestion. The injected extract was
      further purified and concentrated using an on-line trap column in the nano-LC
      system. Detection and confirmation were achieved by monitoring a unique peptide
      segment of rhEPO/DPO/PEG-EPO using nano-liquid chromatography-tandem mass
      spectrometry equipped with a nanospray ionisation source operated in the selected
      reaction monitoring mode. rhEPO, DPO and PEG-EPO can be confirmed at 0.1, 0.2 and
      1.0 ng/mL, respectively, in equine plasma.

PMID- 20148244
TI  - Combined exposure of peripubertal male rats to the endocrine-disrupting compound
      atrazine and power-frequency electromagnetic fields causes degranulation of
      cutaneous mast cells: a new toxic environmental hazard?
AB  - The effects of single and combined treatments of the endocrine-disrupting
      compound atrazine and the power-frequency electromagnetic fields (EMFs) were
      investigated on cutaneous mast cells in juvenile/peripubertal male Wistar rats.
      Animals were divided into six groups: (1) 4 h/day exposure to EMFs (50 Hz), (2)
      20 mg/kg of body weight (bw) of atrazine, (3) 200 mg/kg bw of atrazine, (4) EMFs
      with 20 mg/kg bw of atrazine, (5) EMFs with 200 mg/kg bw of atrazine, and (6)
      control. Both the atrazine and the combined treatments, but not the single EMF
      exposure, increased the number of degranulated mast cells. Statistically
      significant differences were demonstrated between the control and both of the
      combined treatments (p<0.01 and p<0.001, respectively). Additionally, low and
      high doses of atrazine combined with the EMFs were found significantly different
      when compared to the EMF group alone (both at p<0.001). Considering the
      biological importance of mast cells in cutaneous immune reactions, future studies
      should reveal whether combined exposures to chemical and physical environmental
      agents pose a serious health risk.

PMID- 20148245
TI  - Developmental toxicity of endocrine disrupters bisphenol A and vinclozolin in a
      terrestrial isopod.
AB  - Studies of the effects of endocrine-disrupting compounds (EDCs) on invertebrates
      are still largely underrepresented. This work aims to fill this gap by assessing
      the effects of bisphenol A (BPA) and vinclozolin (Vz) on the terrestrial isopod
      Porcellio scaber (common rough woodlouse). Male adult and sexually
      undifferentiated juvenile woodlice were exposed to the toxicants. Effects on
      molting regime and growth were investigated independently for males and female
      woodlice after sexual differentiation. Both chemicals elicited developmental
      toxicity to P. scaber by causing overall decreased growth. Nevertheless, BPA
      induced molting, whereas Vz delayed it. Although the LC50 values for juvenile and
      adult survival were fairly similar, juvenile woodlice showed an increased chronic
      sensitivity to both chemicals, and female woodlice were most the sensitive to
      BPA. We recommend the use of adults, juveniles, female, and male woodlice, as
      well as a large range of toxicant concentrations, to provide valuable information
      regarding differential dose responses, effects, and threshold values for EDCs.

PMID- 20148246
TI  - Massive intra-atrial thrombosis in an 11-year-old child with restrictive
      cardiomyopathy.

PMID- 20148247
TI  - Re: Xu et al.: "Renal cell carcinoma: real-time contrast-enhanced ultrasound
      findings".

PMID- 20148248
TI  - Natural resource management at four social scales: psychological type matters.
AB  - Understanding organisation at different social scales is crucial to learning how
      social processes play a role in sustainable natural resource management. Research
      has neglected the potential role that individual personality plays in decision
      making in natural resource management. In the past two decades natural resource
      management across rural Australia has increasingly come under the direct
      influence of voluntary participatory groups, such as Catchment Management
      Authorities. The greater complexity of relationships among all stakeholders is a
      serious management challenge when attempting to align their differing aspirations
      and values at four social institutional scales-local, regional, state and
      national. This is an exploratory study on the psychological composition of groups
      of stakeholders at the four social scales in natural resource management in
      Australia. This article uses the theory of temperaments and the Myers-Briggs Type
      Indicator (MBTI) to investigate the distribution of personality types. The
      distribution of personality types in decision-making roles in natural resource
      management was markedly different from the Australian Archive sample. Trends in
      personality were found across social scales with Stabilizer temperament more
      common at the local scale and Theorist temperament more common at the national
      scale. Greater similarity was found at the state and national scales. Two
      temperaments comprised between 76 and 90% of participants at the local and
      regional scales, the common temperament type was Stabilizer. The dissimilarity
      was Improviser (40%) at the local scale and Theorist (29%) at the regional scale.
      Implications for increasing participation and bridging the gap between community
      and government are discussed.

PMID- 20148249
TI  - Hydrolytic dechlorination of chlorothalonil by Ochrobactrum sp. CTN-11 isolated
      from a chlorothalonil-contaminated soil.
AB  - A bacterial strain, designated as CTN-11, capable of degrading chlorothalonil
      (CTN), was isolated from a chlorothalonil-contaminated soil in China. Based on
      the morphological, biochemical characteristics and comparative analysis of the
      16S rRNA genes, strain CTN-11 was identified as Ochrobactrum sp. Strain CTN-11
      could degrade 50 mg l(-1) CTN to a non-detectable level within 48 h, and
      efficiently degrade CTN in a relatively broad range of temperatures from 20 to 40
      degrees C and initial pH values from 6.0 to 9.0. The new isolate differed from
      those previously reported CTN co-metabolic degraders by transforming CTN in the
      absence of other carbon sources. A glutathione S-transferase (GST) coding gene,
      which showed 88% sequence similarity with that from Ochrobactrum anthropi SH35B,
      was cloned from strain CTN-11. However, the gene was not functionally expressed
      in the presence of glutathione, indicating that CTN was not reductively
      dechlorinated by thiolytic substitution catalyzed by GST in strain CTN-11. The
      metabolite hydroxyl-trichloroisophthalonitrile (CTN-OH) produced during CTN
      anaerobic degradation was identified based on tandem MS/MS, confirming that
      hydrolytic dechlorination was involved in the CTN degradation. The removal of CTN
      by strain CTN-11 in sterile and non-sterile soils was also studied. In both soil
      samples, 50 mg kg(-1) CTN could be degraded to an undetectable level within 3
      days. This study highlights an important potential use of strain CTN-11 for the
      cleanup of CTN-contaminated sites and presents a hydrolytic dechlorination
      reaction of CTN by a pure culture.

PMID- 20148250
TI  - Characterization of Comamonas thiooxidans sp. nov., and comparison of thiosulfate
      oxidation with Comamonas testosteroni and Comamonas composti.
AB  - Comamonas thiooxidans (strain S23(T)) capable of oxidizing thiosulfate under a
      mixotrophic growth condition was isolated from a sulfur spring. DNA-DNA homology
      study showed 55% similarity with Comamonas testosteroni KCTC2990(T) and 52% with
      Comamonas composti LMG24008(T), the nearest phylogenetic relative (16S rRNA
      sequence similarity <97%). Comparative genomic fingerprinting by using ERIC and
      Rep-PCR further delineated species identity of the strain S23(T) for which
      Comamonas thiooxidans sp. nov. is proposed. In addition, thiosulfate oxidation
      potential of the strain S23(T) was compared with Comamonas testosteroni and
      Comamonas composti.

PMID- 20148251
TI  - Diagnosis of liver metastases: value of diffusion-weighted MRI compared with
      gadolinium-enhanced MRI.
AB  - OBJECTIVE: The full diagnostic value of diffusion-weighted (DW) MRI in the
      evaluation of liver metastases remains uncertain. The aim of the present study
      was to assess the diagnostic accuracy of DW-MRI and contrast-enhanced MRI (CE
      MRI) using extracellular gadolinium chelates, with the reference standard
      established by consensus interpretation of confirmatory imaging and
      histopathologic data. METHODS: MR examinations of 51 patients with extrahepatic
      malignancies were retrospectively reviewed by two independent observers who
      assessed DW-MRI and CE-MRI for detection of liver metastases. RESULTS: By
      reference standard, 93 liver lesions (49 metastases and 44 benign lesions) were
      identified in 27 patients, 11 patients had no liver lesions, and 13 patients had
      innumerable metastatic and/or benign lesions. There was no difference in
      diagnostic performance between the two methods for either observer for the
      diagnosis of metastatic lesions per patient. For per-lesion analysis, sensitivity
      of DW-MRI was equivalent to CE-MRI for observer 1 (67.3% vs. 63.3%, p = 0.67),
      but lower for observer 2 (65.3% vs. 83.7%, p = 0.007). By pooling data from both
      observers, the sensitivity of DW-MRI was 66.3% (65/98) and 73.5% (72/98) for CE
      MRI, with no significant difference (p = 0.171). CONCLUSION: DW-MRI is a
      reasonable alternative to CE-MRI for the detection of liver metastases.

PMID- 20148252
TI  - Spinal cord compression in children with Wilms' tumour.
AB  - PURPOSE: To document the clinical, imaging and histopathological features of five
      children with paraplegia due to Wilms' tumour (WT), highlighting therapeutic
      options and patient outcome in a developing country. METHODS: Patients with WT
      and paraplegia seen at the Department of Paediatric Surgery since 1984 form the
      study cohort. Patient demographics, duration of neurological symptoms, stage of
      primary tumour, therapeutic intervention and outcome were recorded. Histology of
      the primary tumours and paraspinal or epidural biopsies were reviewed. RESULTS:
      Five patients with WT and paraplegia were identified. Imaging showed epidural
      masses with paraspinal disease, cord displacement and compression. Four patients
      have died. Of the two patients with neurological recovery, one relapsed 4 months
      later. Histology revealed triphasic WT with one case showing anaplasia.
      Paraspinal or epidural biopsies confirmed WT with post-treatment changes. Three
      biopsies showed lymphovascular, perineurial and intraneural tumour invasion and
      one showed epidural venous invasion. CONCLUSION: Although rare, WT-associated
      spinal disease may cause permanent neurological deficit, adding considerably to
      the burden of disease. In developing countries where patients present late, the
      prognosis is poor, however surgery may provide immediate relief of compression
      symptoms and biopsy material. The treatment of choice will depend on the
      facilities available and the clinical circumstances.

PMID- 20148253
TI  - Complications and treatment failures of video-assisted thoracoscopic debridement
      for pediatric empyema.
AB  - PURPOSE: Video-assisted thoracoscopic debridement (VATD) is a well-established
      intervention to treat pediatric empyema. There is ongoing controversy at what
      stage in the treatment algorithm it should be utilized. To shed further light
      onto this debate, we reviewed our institutional experience looking for factors
      predicting treatment failure or complications of VATD. METHODS: We
      retrospectively analyzed data on patients that had undergone VATD for empyema
      from 1995 to 2008. We used independent sample t tests and Chi-square tests (SPSS)
      for statistical analysis. RESULTS: One hundred and fifty-two procedures in 151
      patients [81 male (53.6%)] were identified. In 146 (96.7%) the etiology of the
      empyema was pulmonary, in 3 (1.98%) due to an infectious abdominal process and in
      2 (1.3%) due to abdominal trauma. 118 patients (78.1%) were transferred from
      outside hospitals. 107 (70.1%) underwent VATD primarily, 44 (29.1%) following
      another procedure. The overall complication rate was 13.8%, most of which were
      minor. Treatment failures occurred in seven patients, resulting in three
      reoperations; two patients died. The average length of stay was 10.1 days, but
      was significantly longer if VATD followed another procedure or if a complication
      occurred. The risk for complications correlated with older age (6.2 vs. 8.8
      years, p = 0.023) and lower hematocrit on admission (31.1 vs. 27.9%, p = 0.006).
      CONCLUSIONS: VATD provided effective treatment for pediatric empyema.
      Complications were mostly minor, occurring more frequently in older patients and
      those with a lower admission hematocrit. Early VATD decreased the length of
      hospitalization.

PMID- 20148254
TI  - High incidence of post-dural puncture headache in patients with spinal saddle
      block induced with Quincke needles for anorectal surgery: a randomised clinical
      trial.
AB  - PURPOSE: Spinal saddle block represents nearly the ideal anaesthesia technique
      for anorectal surgery. Post-dural puncture headache (PDPH) is a dreaded
      complication but can be decreased by the use of non-cutting spinal needles to
      rates less than 1%. Though, cutting Quincke type needles are still widely used
      for economic reasons, leading to a higher rate of PDPH. We performed this study
      to demonstrate a reduction of PDPH by the use of very small 29-G compared with
      commonly used 25-G Quincke type spinal needles. METHODS: Two hundred sixteen
      adult patients (male/female, 19-83 years, ASA status I-III) were randomised 1:1
      to groups, in which either a 25-G or a 29-G Quincke type spinal needle was used
      for a spinal saddle block. The incidence of PDPH was assessed during 1 week after
      surgery. RESULTS: Thirty-nine of 216 patients developed PDPH but there was no
      difference between the two needle sizes (25-G, n = 18/106 vs. 29-G, n = 21/110, p
      = 0.6870). Women suffered significantly more from PDPH than men (23/86 vs.
      16/130, p = 0.0069). Ambulatory patients had a later onset of PDPH than in
      patients (24 h [0.5-72] vs. 2 h [0.2-96], p = 0.0002) and the headache was more
      severe in these patients (NRS 7 [2-10] vs. NRS 3 [1-8], p = 0.0009). CONCLUSIONS:
      The use of 29-G compared with 25-G Quincke needles led to no reduction of PDPH
      and is considerably higher compared with data from pencil-point needles. The use
      of non-cutting or pencil-point spinal needles should become the standard for
      performing spinal saddle block.

PMID- 20148255
TI  - Damage control with abdominal vacuum therapy (VAC) to manage perforated
      diverticulitis with advanced generalized peritonitis--a proof of concept.
AB  - PURPOSE: Perforated diverticulitis with advanced generalized peritonitis is a
      life-threatening condition requiring emergency operation. To reduce the rate of
      colostomy formation, a new treatment algorithm with damage control operation,
      lavage, limited closure of perforation, abdominal vacuum-assisted closure (VAC;
      V.A.C.), and second look to restore intestinal continuity was developed. METHODS:
      This algorithm allowed for three surgical procedures: primary anastomosis +/- VAC
      in stable patients (group I), but damage control with lavage, limited resection
      of the diseased colonic segment, VAC and second-look operation with delayed
      anastomosis in patients with advanced peritonitis or septic shock (group II), and
      Hartmann procedure was done for social reasons in stable patients (group III)
      RESULTS: All 27 consecutive patients (16 women; median age 68 years) requiring
      emergency laparotomy for perforated diverticulitis (Hinchey III/IV) between
      October 2006 and September 2008 were prospectively enrolled in the study. No
      major complications were observed in group I (n = 6). Nine patients in group II
      (n = 15) had intestinal continuity restored during a second-look operation, of
      whom one patient developed anastomotic leakage. The median length of stay at
      intensive care unit was 5 days. Considering an overall mortality rate of 26% (n =
      7), the rate of anastomosis in surviving patients was 70%. CONCLUSIONS: Damage
      control with lavage, limited bowel resection, VAC, and scheduled second-look
      operation represents a feasible strategy in patients with perforated
      diverticulitis (Hinchey III and IV) to enhance sepsis control and improve rate of
      anastomosis.

PMID- 20148256
TI  - Involvement of IL-17F via the induction of IL-6 in psoriasis.
AB  - Recently, the important role of T helper 17 (Th17) cells in psoriasis has been
      clarified; however, the role of IL-17F produced by Th17 cells is still not fully
      understood. IL-6 exhibits multiple biologic functions, such as regulation of
      immunological responses including those in psoriatic reactions. Therefore, we
      examined the production of IL-6 protein in normal human epidermal keratinocytes
      (NHEKs) stimulated by IL-17F, TNF-alpha, IL-17A, and IL-17A in combination with
      TNF-alpha, and PBS control. We then examined the expression of IL-6 mRNA in mouse
      skin after intradermal injection of IL-17F. Finally, IL-17F expression in skin
      biopsy specimens from psoriasis patients was examined by immunohistochemistry.
      The results showed that IL-17F induced production of IL-6 in NHEKs in a time
      dependent manner. This could be attenuated by chimeric inhibitor blocking the IL
      17 receptor. The amounts of IL-6 stimulated by IL-17F were much higher than those
      stimulated by TNF-alpha or IL-17A. IL-6 was also significantly upregulated via
      synergistic stimulation with IL-17A plus TNF-alpha. The expression of IL-6 mRNA
      24 h after IL-17F injection in the mouse skin was 3.2-fold higher than that in
      the control group. Immunohistochemistry of inflammatory cells in the dermis
      demonstrated a large number of CD4(+) T cells showing IL-17F positivity in
      psoriatic skin lesions, but few or none in non-lesional psoriatic skin. Our
      results indicate that IL-17F produced by CD4(+) T cells causes the inflammation
      in psoriasis partly through induction of IL-6 in keratinocytes.

PMID- 20148257
TI  - Evaluation of an automated auditory brainstem response in a multi-stage infant
      hearing screening.
AB  - An automated auditory brainstem response (AABR) method, the Maico MB-11 with
      BERAphone, has been developed for hearing screening in newborns. The aim of this
      study was to test the validity of this automated ABR screening method in a
      multistage newborn hearing screening (NHS). We applied a "five level" protocol
      using transient evoked otoacoustic emission (TEOAE), AABR-MB-11 with BERAphone
      and conventional auditory brainstem response (ABR). TEOAE, AABR, and conventional
      ABR testing were performed by ENT specialists experienced in neonatal screening
      techniques. Among the 8,671 newborns tested (males 3,889; females 4,782), only 42
      newborns were lost to follow-up and the final false-positive rate was of 0.03%.
      Our experience highlights that for the neonatal period, conventional auditory
      brainstem response is the most reliable method for assessing the hearing level
      and minimizing the false-positive rate. Although AABR (performed by ENT
      specialists experienced in neonatal screening techniques) is easy to use, fast
      and with a good compliance, the device is unable to provide accurate and certain
      diagnosis on the degree of hearing loss to allow a proper treatment.

PMID- 20148258
TI  - Reproducibility and validity of the stair-climb test for fire fighters.
AB  - PURPOSE: A new job-specific test for fire fighters, the stair-climb test (FFstair
      climb) was evaluated for reproducibility and validity for use in future workers'
      health surveillance. METHODS: The FFstair-climb was performed at three times by
      20 male fire fighters (one and three weeks in between test and retest) to examine
      the reliability and agreement. An intraclass correlation coefficient (ICC) and
      standard error of measurement (SEM) were calculated. In addition, 45 fire
      fighters (2 women, 43 men) performed the test once, while heart rate and testing
      time were monitored, to study the content validity. Construct validity was tested
      by correlating both self-rated and supervisor-rated work ability scores with
      testing time. RESULTS: The reliability, reflected by the ICC, was high for the
      one-week and the three-week test-retest period, 0.82 and 0.91, respectively. The
      mean testing time for the FFstair-climb was about 65 s; the agreement showed SEMs
      of 5.4 s at the one-week test-retest period and 3.8 s at the three-week test
      retest period. Content validity was good in 78% of the fire fighters, while the
      construct validity between testing times and work ability ratings was not
      sufficient (r < 0.30). CONCLUSIONS: The FFstair-climb can be used in the Workers'
      Health Surveillance of fire fighters as a reproducible instrument, with good
      content validity. Testing criterion validity in future research would be an
      appropriate next step.

PMID- 20148259
TI  - Relationship between occupational exposure to ionizing radiation and mortality at
      the French electricity company, period 1961-2003.
AB  - PURPOSE: Epidemiological studies in nuclear industry workers can produce relevant
      information to better appreciate the health risks related to chronic external
      exposure to low doses of ionizing radiation (IR). This work examined the
      relations between exposure to IR and mortality in workers at the French
      Electricity Company (EDF), followed up to year 2003. METHODS: Permanent staff who
      had worked for at least 1 year at EDF during period 1961-1994 and who had been
      monitored for exposure to IR were included (n = 22,393). One-sided trend tests
      for mortality according to cumulative dose and relative risks at 100 mSv were
      estimated using Poisson regression. Main analyses were stratified on age, sex,
      calendar time and education. RESULTS: A total of 874 deaths occurred, and 66
      workers were lost to follow-up. Median age at end of follow-up was 48. None of
      the causes of death investigated increased significantly according to dose,
      except cerebrovascular diseases (p = 0.01), but this last observation was based
      on only 22 cases. CONCLUSIONS: These results do not allow dismissing a possible
      influence of IR on cancer risk in this population. The cohort is still relatively
      young and therefore confidence intervals for estimated relative risks remain
      wide, although they have considerably narrowed since a previous analysis. Chance
      is a possible explanation for the association between IR and cerebrovascular
      mortality, due to the low number of cases on which it is based. These results
      thus need to be stabilized by conducting joint analyses with similar cohorts.

PMID- 20148260
TI  - Action and behavior: a free-energy formulation.
AB  - We have previously tried to explain perceptual inference and learning under a
      free-energy principle that pursues Helmholtz's agenda to understand the brain in
      terms of energy minimization. It is fairly easy to show that making inferences
      about the causes of sensory data can be cast as the minimization of a free-energy
      bound on the likelihood of sensory inputs, given an internal model of how they
      were caused. In this article, we consider what would happen if the data
      themselves were sampled to minimize this bound. It transpires that the ensuing
      active sampling or inference is mandated by ergodic arguments based on the very
      existence of adaptive agents. Furthermore, it accounts for many aspects of motor
      behavior; from retinal stabilization to goal-seeking. In particular, it suggests
      that motor control can be understood as fulfilling prior expectations about
      proprioceptive sensations. This formulation can explain why adaptive behavior
      emerges in biological agents and suggests a simple alternative to optimal control
      theory. We illustrate these points using simulations of oculomotor control and
      then apply to same principles to cued and goal-directed movements. In short, the
      free-energy formulation may provide an alternative perspective on the motor
      control that places it in an intimate relationship with perception.

PMID- 20148261
TI  - Revisiting Christfried Jakob's concept of the dual onto-phylogenetic origin and
      ubiquitous function of the cerebral cortex: a century of progress.
AB  - This paper revisits a concept combining the evolution, ontogeny and
      histophysiology of the cerebral cortex, presented, in a quest to explain
      cognition and behavior, by the neurobiologist Christfried Jakob (1866-1956) at
      the Second Annual Meeting of the International Society for Medical Psychology and
      Psychotherapy, organized by Oskar Vogt (1870-1959) in Munich in 1911. Jakob
      suggested a dual onto-phylogenetic origin and a ubiquitous cortical function,
      claiming that most receptive pathways end up in an 'outer fundamental layer',
      which derives from the rhinencephalic apparatus, whereas the 'inner fundamental
      layer' contains effector elements and derives from the striatum. With advancing
      evolution, the two fundamental layers become intermingled. By attributing a
      functional homogeneity to the cortex, Jakob contradicted the theories of Flechsig
      and Cajal on 'association' and 'mnemonic' areas. The merit of Jakob's concept
      rests, a century later, with the current resurgence of biological research at the
      evolutionary-developmental interface and the broadening anticipated from the re
      integration of these two fields, especially by adding a functional dimension to
      the morphological traits.

PMID- 20148262
TI  - Transient hepatitis B surface antigen circulation after Infanrix-Hexa: a case
      report and review of the literature.
AB  - The authors describe the case of a 70-day-old boy who was mistakenly diagnosed as
      suffering from acute hepatitis B, when he presented with persistent unconjugated
      hyperbilirubinemia and transaminasemia and was found to be seropositive for the
      hepatitis B surface antigen. The antigenemia was transient and related to his
      recent immunization with Infanrix-Hexa. Caution is required during interpretation
      of a positive HBsAg test that is obtained within 28 days after vaccination
      against hepatitis B.

PMID- 20148263
TI  - Safety, immunogenicity and immediate pain of intramuscular versus subcutaneous
      administration of a measles-mumps-rubella-varicella vaccine to children aged 11
      21 months.
AB  - This study compared intramuscular and subcutaneous administration of two doses of
      measles-mumps-rubella-varicella (MMRV) combination vaccine (Priorix-Tetra,
      GlaxoSmithKline Biologicals) in children. Healthy children (N = 328) were
      randomised to receive MMRV either intramuscularly or subcutaneously.
      Reactogenicity was similar between treatment groups for immediate vaccination
      pain, vaccination site pain, redness and incidence of fever and rashes. Slightly
      less vaccination site swelling occurred during days 0-3 of the post-vaccination
      period after intramuscular administration. Seroconversion rates for all
      components, 42-56 days post-dose 2, ranged from 99.3% to 100% in the
      intramuscular group and from 98.6% to 100% in the subcutaneous. Cell-mediated
      immunity data supported the humoral immunogenicity findings. In summary, the MMRV
      vaccine is well tolerated and highly immunogenic when administered either
      subcutaneously or intramuscularly to children in the second year of life.

PMID- 20148264
TI  - Surgical treatment for early hepatocellular carcinoma: comparison of resection
      and liver transplantation.
AB  - PURPOSE: The optimum strategy, hepatic resection (HR) or liver transplantation
      (LT), for treatment of early hepatocellular carcinoma (HCC) associated with liver
      diseases of Child-Pugh A is far from established. The aim of this study was to
      compare and determine which strategy is optimal for HCC fulfilling the Milan
      criteria. METHODS: Consecutive data were collected in 1,018 HCC patients treated
      with HR and 89 HCC patients listed for LT (1 drop out for HCC progression)
      between January of 2003 and December of 2007. RESULTS: The independent prognostic
      factors identified by multivariate analysis were tumor size-plus-number,
      microscopic venous invasion, and operation type (LT or HR). When tumor size-plus
      number was < or =4 or microscopic venous invasion was absent, there was no
      significant difference in overall survival (OS) between the LT and HR group. When
      tumor size-plus-number was >4 or microscopic venous invasion was present, OS was
      higher in the LT group. CONCLUSIONS: Since the pathological microscopic venous
      invasion was not easily available before operation which is limitation for
      widespread clinical use, thus in practice, we concluded that, for early HCC
      associated with Child-Pugh A cirrhosis, when tumor size-plus-number is >4, LT
      provides the best cure; when it is < or =4, HR remains the initial treatment of
      choice.

PMID- 20148265
TI  - Gene expression profiling during the byssogenesis of zebra mussel (Dreissena
      polymorpha).
AB  - Since its invasion to the North American waters 20 years ago, the zebra mussel
      (Dreissena polymorpha) has negatively impacted the ecosystems through its firm
      underwater adhesion. The molecular mechanisms governing the functions of the
      zebra mussel byssus, the main structure responsible for maintaining the
      underwater adhesion, have received little attention. Our previously developed
      zebra mussel foot byssus cDNA microarray was applied in this study to identify
      the genes involved in different stages of the byssal threads generation. Byssal
      threads of zebra mussels were manually severed under laboratory conditions and
      the formation of new byssal threads was followed over a 3 week course. By
      comparing the gene expression profiles in different stages of byssal threads
      generation (byssogenesis) to their baseline values, we found that the number of
      unique byssus genes differentially expressed at 12-h, 1, 2, 3, 4, 7, and 21 days
      post-treatment was 13, 13, 20, 17, 16, 20, and 29, respectively. Comparisons were
      also made between two subsequent samples (e.g., 12 h vs. 1, 1 vs. 2 days, 2 vs. 3
      days, and so on). Seven differentially expressed genes were selected for
      validation by using quantitative reverse transcription PCR (qRT-PCR) and the
      results were consistent with those from the microarray analysis. By using
      fluorescent in situ hybridization, we found that two microarray identified genes,
      BG15_F03-DPFP and BG16_H05-EGP, were expressed in two major byssus glands located
      in the zebra mussel foot: the stem-forming gland and plaque-forming gland,
      respectively. Moreover, the qRT-PCR of seven microarray identified genes with
      different zebra mussel samples suggested that they were also expressed in other
      mussel tissues beside the foot, albeit at much lower levels. This suggested that
      the microarray identified genes were produced primarily by the foot, and were
      likely associated with byssogenesis. The differentially expressed genes
      identified in this study indicated that multiple molecules are involved in
      byssogenesis, most likely performing multiple functions during the generation of
      byssal threads. These results obtained herein represent the first logical step
      toward understanding underwater attachment mechanisms employed by this invasive
      species.

PMID- 20148266
TI  - Performance of bench-scale membrane bioreactor under real work conditions using
      pure oxygen: viscosity and oxygen transfer analysis.
AB  - Pure oxygen to supply the aerobic condition was used in the performance of a
      bench-scale submerged membrane bioreactor (MBR). The pilot plant was located in
      the wastewater treatment plant of the city of Granada (Spain) and the
      experimental work was divided into two stages (Unsteady state and steady state
      conditions). Operation parameters (MLSS, MLVSS and dissolved oxygen
      concentration) and physical characteristics (temperature, conductivity, pH, COD
      and BOD(5)) were daily monitored. The results showed the capacity of the MBR
      systems to remove organic material under a hydraulic retention time of 18.46 h
      and sludge retention time of 18.6 days. Therefore, Viscosity of the sludge and
      alphakLa-factor of the aeration, were determinate in the steady stage condition
      to understand the behavior of the system when pure oxygen has been used to supply
      the aerobic conditions of the MBR system showed an alpha-factor of 0.238 when the
      viscosity of the system was 4.04 Cp.

PMID- 20148267
TI  - Controlling selectivity and enhancing yield of flavonoid glycosides in
      recombinant yeast.
AB  - Flavonoid glycosides are known for their medicinal properties and potential use
      as natural sweeteners. In this study, Saccharomyces cerevisiae expressing a
      flavonoid glucosyltransferase from Dianthus caryophyllus was used as a whole-cell
      biocatalyst. The yeast system's performance was characterized using the flavanone
      naringenin as a model substrate for the production of naringenin glycosides. It
      was found that final naringenin glycoside yields increased in a dose-dependent
      manner with increasing initial naringenin substrate concentrations. However,
      naringenin concentrations >0.5 mM did not give further enhancements in glycoside
      yield. In addition, a method for controlling overall selectivity was discovered
      where the glucose content in the culture medium could be altered to control the
      selectivity, making either naringenin-7-O-glucoside (N7O) or naringenin-4'-O
      glucoside (N4O) the major products. The highest yields achieved were 87 mg/L of
      N7O and 82 mg/L of N4O using 40MSGI and 2xMSGI media, respectively. The effects
      of two intermediates involved in UDP-glucose biosynthesis, uridine 5'
      monophosphate (UMP) and orotic acid, on glycoside yields were also determined.
      Addition of UMP to the culture medium significantly decreased glycoside yield. In
      contrast, addition of orotic acid to the culture medium significantly enhanced
      the glycoside yield and shifted the selectivity toward N7O. The highest
      naringenin glycoside yield achieved using 10 mM orotic acid in the 40MSGI media
      was 155 mg/L, a 71% conversion of substrate to product.

PMID- 20148268
TI  - Modeling effects of granules on the start-up of anaerobic digestion of dairy
      wastewater with Langmuir and extended Freundlich equations.
AB  - The effects of granules-inocula on the start-up of anaerobic reactors treating
      dairy manure were studied in a batch-fed reactor. The effects of start-up period
      and ratio of granules to feed were analyzed. Results indicated that the effects
      of start-up period could be described by Langmuir model, while the Extended
      Freundlich model could be used to model the effects of ratio of granules to feed
      on cumulative biogas production. In addition, transmission electron microscopes
      (TEM) and scanning electron microscope analysis were conducted to elucidate the
      distribution of microbial population and micro-colonies in granules and manure.
      From the TEM micrographs analyses, the ratios the Syntrophobacter and methanogens
      in granule and manure were shown to be 1.57 +/- 0.42 and 0.22 +/- 0.20,
      respectively. These results demonstrated that granules-inocula could reduce the
      period required for onset of biogas by 25%.

PMID- 20148269
TI  - Breeding behaviour of Kunzea pomifera (Myrtaceae): self-incompatibility,
      intraspecific and interspecific cross-compatibility.
AB  - To examine breeding system characteristics of the endemic Australian prostrate
      shrub Kunzea pomifera, artificial hybridisations were undertaken using thirteen
      different genotypes of K. pomifera, to elucidate: (1) self-incompatibility, (2)
      intraspecific cross-compatibility in the species and (3) interspecific cross
      compatibility with each of K. ambigua and K. ericoides. K. pomifera exhibited
      very low self-compatibility, with the barrier to self-fertilisation being
      prevention of pollen-tube growth in the style or ovary. Following intraspecific
      pollination amongst a number of different genotypes of K. pomifera, 38.4% of
      pollinated flowers developed fruit; arrest of compatible pollen-tubes in the
      style, preventing fertilisation, contributes to the low fruit set in this
      species. Interspecific compatibility was examined between K. pomifera (pistillate
      parent) and K. ambigua (staminate parent) where seed set per pollinated flower
      (4.47) was not significantly different from intraspecific crosses (4.66). In
      crosses between K. pomifera (pistillate parent) and K. ericoides as staminate
      plant, 0.037% of pollinated flowers produced fruit, with 0.0075 seeds per
      pollinated flower. Reproductive barriers between these two species were evident
      in the style of K. pomifera, where the growing tips of the K. ericoides pollen
      tubes swelled and ceased to grow.

PMID- 20148271
TI  - Tentorial meningiomas with special aspect to the tentorial fold: management,
      surgical technique, and outcome.
AB  - BACKGROUND: From a surgical perspective, tentorial fold (TF) meningiomas (TFM)
      are a unique entity of tumors. They involve the supra- and infratentorial space
      and often are in close contact to the cavernous sinus, cranial nerves, and the
      mesencephalon. Complete resection is challenging and can be hazardous. We present
      our experience with this rare tumor entity and demonstrate the surgical outcome
      related to a topographical classification. METHODS: A retrospective analysis on
      21 consecutive patients (female/male ratio 17/4) with meningiomas originating
      from the TF, who underwent surgery between 1992 and 2005 in our clinic, was
      performed. The follow-up period ranged from 6 to 93 months. The cases were
      classified according to tumor extension in three different types: type I, TF
      meningiomas with compression of the brain stem; type II, with extension into the
      anterior portion of middle fossa; and type III, a combination of type I and II.
      Depending on tumor location, surgical approaches consisted of pterional (nine
      cases), subtemporal (nine cases), or combined subtemporal-pterional craniotomies
      (three cases). We defined transient and persistent operative complications in
      relation to Simpson grade and TF classification. RESULTS: Tumor size ranged from
      1 to 6 cm in diameter, with a median at 2.5 cm. The presenting symptoms of the
      patients were anisocoria (six cases), diplopia (six cases), ptosis (five cases),
      hemianopia (four cases), and ataxia (two cases). Extent of tumor resection was
      Simpson grade II in 19 patients, grade III in one patient, and grade IV in one
      patient. There was no operative mortality (first 30 days after surgery). The rate
      of postoperative transient new neurological deficits was found at 9.5%, the rate
      of permanent at 33%. The neurological deficits at admission recovered in two
      patients. CONCLUSION: In the majority of patients with TF meningiomas, total
      resection can be achieved through a pterional, subtemporal, or combined
      approaches but at a substantial toll in terms of permanent morbidity.
      Radiotherapy after volume reductive surgery in TFM type II and III and
      decompression of eloquent anatomical structures with low tolerance of radiation
      should be considered.

PMID- 20148272
TI  - Fulminant fatal meningitis following partial resection of an endodermal cyst.

PMID- 20148270
TI  - A new concept for the differential diagnosis and therapy of anaemia in cancer
      patients.
AB  - PURPOSE: This study aimed to prove the usefulness of the diagnostic plot, using
      the haemoglobin content of reticulocytes as a measure of functional iron
      deficiency (FID) and the ferritin index as a measure of iron availability, to
      customise anaemia treatment in cancer patients. METHODS: Based on results of this
      plot, cancer patients fulfilling practice guideline criteria to receive
      erythropoiesis-stimulating agents (ESAs) were allocated to treatment with ESAs
      alone, iron alone or the combination of both. Primary endpoint was the percentage
      of patients identified to require iron in addition or as an alternative to ESA
      therapy. RESULTS: Out of 303 patients screened, 286 were allocated to treatment:
      204 patients were normochromic and iron replete and treated with ESAs alone, 22
      had both FID and anaemia of chronic disease and were treated with ESAs and
      parenteral iron, and 60 were iron-depleted and treated with iron only. After 8
      weeks, a haemoglobin increase >1 g/dL from baseline was shown by 56% of patients
      treated with ESAs alone, by 100% of patients receiving the combination, by 50% of
      normochromic and by 73% of hypochromic iron-depleted patients receiving iron
      only. Acute phase reaction did not diminish the response rate to ESAs.
      CONCLUSIONS: The diagnostic plot was superior to transferrin saturation and
      ferritin in predicting iron availability in hypochromic patients treated with
      ESAs and proved useful to select treatment for anaemia in cancer patients.

PMID- 20148273
TI  - Division of cell nuclei, mitochondria, plastids, and microbodies mediated by
      mitotic spindle poles in the primitive red alga Cyanidioschyzon merolae.
AB  - To understand the cell cycle, we must understand not only mitotic division but
      also organelle division cycles. Plant and animal cells contain many organelles
      which divide randomly; therefore, it has been difficult to elucidate these
      organelle division cycles. We used the primitive red alga Cyanidioschyzon
      merolae, as it contains a single mitochondrion and plastid per cell, and
      organelle division can be highly synchronized by a light/dark cycle. We
      demonstrated that mitochondria and plastids multiplied by independent division
      cycles (organelle G1, S, G2 and M phases) and organelle division occurred before
      cell-nuclear division. Additionally, organelle division was found to be dependent
      on microtubules as well as cell-nuclear division. We have observed five stages of
      microtubule dynamics: (1) the microtubule disappears during the G1 phase; (2)
      alpha-tubulin is dispersed within the cytoplasm without forming microtubules
      during the S phase; (3) alpha-tubulin is assembled into spindle poles during the
      G2 phase; (4) polar microtubules are organized along the mitochondrion during
      prophase; and (5) mitotic spindles in cell nuclei are organized during the M
      phase. Microfluorometry demonstrated that the intensity peak of localization of
      alpha-tubulin changed in the order to spindle poles, mitochondria, spindle poles,
      and central spindle area, but total fluorescent intensity did not change
      remarkably throughout mitotic phases suggesting that division and separation of
      the cell nucleus and mitochondrion is mediated by spindle pole bodies. Inhibition
      of microtubule organization induced cell-nuclear division, mitochondria
      separation, and division of a single membrane-bound microbody, suggesting that
      similar to cell-nuclear division, mitochondrion separation and microbody division
      are dependent on microtubules.

PMID- 20148274
TI  - Between life and death: exploring the sociocultural context of antenatal mental
      distress in rural Ethiopia.
AB  - The high prevalence of antenatal common mental disorders in sub-Saharan Africa
      compared to high-income countries is poorly understood. This qualitative study
      explored the sociocultural context of antenatal mental distress in a rural
      Ethiopian community. Five focus group discussions and 25 in-depth interviews were
      conducted with purposively sampled community stakeholders. Inductive analysis was
      used to develop final themes. Worry about forthcoming delivery and fears for the
      woman's survival were prominent concerns of all participants, but only rarely
      perceived to be pathological in intensity. Sociocultural practices such as
      continuing physical labour, dietary restriction, prayer and rituals to protect
      against supernatural attack were geared towards safe delivery and managing
      vulnerability. Despite strong cultural norms to celebrate pregnancy, participants
      emphasised that many pregnancies were unwanted and an additional burden on top of
      pre-existing economic and marital difficulties. Short birth interval and
      pregnancy out of wedlock were both seen as shameful and potent sources of mental
      distress. The notion that pregnancy in traditional societies is uniformly a time
      of joy and happiness is misplaced. Although antenatal mental distress may be self
      limiting for many women, in those with enduring life difficulties, including
      poverty and abusive relationships, poor maternal mental health may persist.

PMID- 20148276
TI  - Exertional paraspinal muscle rhabdomyolysis and compartment syndrome: a cause of
      back pain not to be missed.
AB  - Exertional compartment syndrome has been described and implicated in pain
      syndromes involving several fascial compartments. This entity is classically
      characterized in the legs, feet and forearms of athletes. We describe a case of
      acute, severe exertional compartment syndrome of the paraspinal muscles in a
      young and healthy male ultimately resulting in significant rhabdomyolysis and
      acute kidney injury. The rarity of the syndrome has prevented the establishment
      of specific guidelines for management; therefore, we will discuss this case in
      the context of similar previously reported cases, contrasting the various
      treatment approaches and outcomes described in previous reports. This discussion
      outlines a syndrome not commonly considered in the differential diagnosis of back
      pain.

PMID- 20148275
TI  - Shared heritability of attention-deficit/hyperactivity disorder and autism
      spectrum disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder
      (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates
      both disorders co-occur with a high frequency, in 20-50% of children with ADHD
      meeting criteria for ASD and in 30-80% of ASD children meeting criteria for ADHD.
      This review will provide an overview on all available studies [family based,
      twin, candidate gene, linkage, and genome wide association (GWA) studies]
      shedding light on the role of shared genetic underpinnings of ADHD and ASD. It is
      concluded that family and twin studies do provide support for the hypothesis that
      ADHD and ASD originate from partly similar familial/genetic factors. Only a few
      candidate gene studies, linkage studies and GWA studies have specifically
      addressed this co-occurrence, pinpointing to some promising pleiotropic genes,
      loci and single nucleotide polymorphisms (SNPs), but the research field is in
      urgent need for better designed and powered studies to tackle this complex issue.
      We propose that future studies examining shared familial etiological factors for
      ADHD and ASD use a family-based design in which the same phenotypic (ADHD and
      ASD), candidate endophenotypic, and environmental measurements are obtained from
      all family members. Multivariate multi-level models are probably best suited for
      the statistical analysis.

PMID- 20148277
TI  - A case of asymptomatic pontine myelinolysis.
AB  - Central pontine myelinolysis is an acquired, non-inflammatory demyelinating
      lesion usually localized in the brainstem pons basis; it usually affects patients
      with a history of chronic alcoholism, malnutrition or dysionemia. The exact
      pathogenesis of myelinolysis is still unclear. A 69-year-old Caucasian male
      presented intensive headache and underwent cranial MRI that showed the typical
      feature of central pontine myelinolysis. Neurological valuation was negative.
      Other examinations included extensive blood tests, electroencephalogram and
      multimodal evoked potentials which all gave normal results. Alcohol abuse and
      malabsorption syndrome were excluded. The medical history revealed a continuative
      use of anti-depressive drugs and exposure to glue for years. Our patient may
      represent one of the rare cases of asymptomatic CPM. The actual reason why he
      presented this lesion is not clear, but we discuss the possible role in the
      etiopathogenesis of his chronic use of anti-depressive drugs and the exposure to
      glue and chemical agents.

PMID- 20148278
TI  - In vitro analysis of human tooth pulp chamber temperature after low-intensity
      laser therapy at different power outputs.
AB  - In vitro studies have provided conflicting evidence of temperature changes in the
      tooth pulp chamber after low-level laser irradiation of the tooth surface. The
      present study was an in vitro evaluation of temperature increases in the human
      tooth pulp chamber after diode laser irradiation (GaAlAs, lambda = 808 nm) using
      different power densities. Twelve human teeth (three incisors, three canines,
      three premolars and three molars) were sectioned in the cervical third of the
      root and enlarged for the introduction of a thermocouple into the pulp chamber.
      The teeth were irradiated with 417 mW, 207 mW and 78 mW power outputs for 30 s on
      the vestibular surface approximately 2 mm from the cervical line of the crown.
      The highest average increase in temperature (5.6 degrees C) was observed in
      incisors irradiated with 417 mW. None of the teeth (incisors, canines, premolars
      or molars) irradiated with 207 mW showed temperature increases higher than 5.5
      degrees C that could potentially be harmful to pulp tissue. Teeth irradiated with
      78 mW showed lower temperature increases. The study showed that diode laser
      irradiation with a wavelength of 808 nm at 417 mW power output increased the pulp
      chamber temperature of certain groups of teeth, especially incisors and
      premolars, to critical threshold values for the dental pulp (5.5 degrees C).
      Thus, this study serves as a warning to clinicians that "more" is not necessarily
      "better".

PMID- 20148279
TI  - Pneumoperitoneum resulting from pneumatosis cystoides intestinalis: a rare
      complication of massive colonic dilatation.

PMID- 20148281
TI  - Oxidative damage to RNA: mechanisms, consequences, and diseases.
AB  - Overproduction of free radicals can damage cellular components resulting in
      progressive physiological dysfunction, which has been implicated in many human
      diseases. Oxidative damage to RNA received little attention until the past
      decade. Recent studies indicate that RNA, such as messenger RNA and ribosomal
      RNA, is very vulnerable to oxidative damage. RNA oxidation is not a consequence
      of dying cells but an early event involved in pathogenesis. Oxidative
      modification to RNA results in disturbance of the translational process and
      impairment of protein synthesis, which can cause cell deterioration or even cell
      death. In this review, we discuss the mechanisms of oxidative damage to RNA and
      the possible biological consequences of damaged RNA. Furthermore, we review
      recent evidence suggesting that oxidative damage to RNA may contribute to
      progression of many human diseases.

PMID- 20148280
TI  - Polo-box domain: a versatile mediator of polo-like kinase function.
AB  - Members of the polo subfamily of protein kinases have emerged as important
      regulators in diverse aspects of the cell cycle and cell proliferation. A large
      body of evidence suggests that a highly conserved polo-box domain (PBD) present
      in the C-terminal non-catalytic region of polo kinases plays a pivotal role in
      the function of these enzymes. Recent advances in our comprehension of the
      mechanisms underlying mammalian polo-like kinase 1 (Plk1)-dependent protein
      protein interactions revealed that the PBD serves as an essential molecular
      mediator that brings the kinase domain of Plk1 into proximity with its
      substrates, mainly through phospho-dependent interactions with its target
      proteins. In this review, current understanding of the structure and functions of
      PBD, mode of PBD-dependent interactions and substrate phosphorylation, and other
      phospho-independent functions of PBD are discussed.

PMID- 20148282
TI  - Immune depression in musculoskeletal trauma.
AB  - The immune responses after musculoskeletal trauma are physiological reactions of
      the organism to restore homeostasis. An imbalance between the early systemic
      inflammatory response syndrome and the later compensatory anti-inflammatory
      response syndrome may be responsible for organ dysfunction and increased
      susceptibility to infections. Cytokines are known to be integral components of
      the immune response, and the balance or imbalance of the different cytokines
      partly controls the clinical course in the patients. The major pro-inflammatory
      cytokines include tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL
      1beta), IL-6, and IL-8. These cytokines are predominantly produced by monocytes
      and macrophages, they mediate overlapping effects, and their actions can be
      additive. TNF-alpha and IL-1beta are early regulators of the immune response, and
      both induce the release of secondary pro-inflammatory cytokines. IL-10 is an anti
      inflammatory cytokine which reduces the synthesis of pro-inflammatory mediators.
      The extent of traumatic damage correlates with the immunological changes and
      determines a graded depression of leucocytes to express cytokines on edotoxin
      exposure. Correspondingly, it has become clinically evident that in unstable
      traumatised patients, the recommendation today is damage control orthopaedics,
      i.e. initial stabilisation of long bone fractures by external fixation followed
      by definitive stabilisation at about 1 week.

PMID- 20148283
TI  - Urinary trypsin inhibitor suppresses excessive generation of superoxide anion
      radical, systemic inflammation, oxidative stress, and endothelial injury in
      endotoxemic rats.
AB  - OBJECTIVE AND DESIGN: The protective effects of ulinastatin, a human urinary
      trypsin inhibitor (UTI), against superoxide radical (O(2)(-*)) generation,
      systemic inflammation, lipid peroxidation, and endothelial injury were
      investigated in endotoxemic rats. MATERIALS AND TREATMENT: Twenty-one Wistar rats
      were allocated to a control group, a UTI group, and a sham group. A bolus of
      lipopolysaccharide (LPS; 3 microg/g) was administered intravenously to the
      control group, a bolus of LPS and UTI (5 U/g) to the UTI group, and a bolus of
      saline to the sham group. METHODS: The O(2)(-*) generated was measured as the
      current in the right atrium using an electrochemical O(2)(-*) sensor. Plasma
      nitrite, high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6, malondialdehyde, and soluble intercellular adhesion molecule
      1 (sICAM-1) were measured 360 min after LPS administration. RESULTS: The O(2)(-*)
      current increased in the control group and was significantly attenuated in the
      UTI group after 55 min (P < 0.05 at 55-60 min, P < 0.01 at 65-360 min). Plasma
      nitrite, HMGB1, TNF-alpha, IL-6, malondialdehyde, and sICAM-1 were attenuated in
      the UTI group. CONCLUSIONS: UTI suppressed excessive O(2)(-*) generation,
      systemic inflammation, lipid peroxidation, and endothelial injury in endotoxemic
      rats.

PMID- 20148284
TI  - Circadian variation in the electroretinogram and the presence of central
      melatonin.
AB  - The light/dark cycle is the most important circadian clock synchronizer for
      mammals and humans. Circadian rhythms of dopamine and melatonin production in the
      retina have been reported to follow the light and dark cycle, but their impact on
      rod and cone functioning is not clear. The purpose of this study was to assess
      diurnal variations (morning vs. evening) in retinal function as measured with the
      photopic and scotopic electroretinogram (ERG). We also tried to correlate our
      results with the presence or absence of melatonin secretion in the saliva.
      Photopic and scotopic luminance-response functions were obtained in 29
      participants at 11:00 (when melatonin should not be present) and 23:00 (when
      melatonin should be present). From the luminance-response function, Vmax, log K
      and slope parameters were derived. In scotopic condition, a significant increase
      of 6% in Vmax amplitude was observed in evening compared to morning (P = 0.03)
      along with a prolonged b-wave implicit time of 8% (P = 0.01) and an increase in
      rod sensitivity in evening compared to morning (P = 0.02). As expected, these
      changes in rod function were accompanied by a higher concentration of melatonin
      in saliva samples in the evening (P = 0.01). In photopic condition, only a
      prolonged a-wave implicit time of 5% was observed in evening when compared to
      morning (P = 0.02). Our findings suggest that the rod system is favored during
      night time, when circulating melatonin is present. Although statistically
      significant changes were observed, the day vs. night difference observed in the
      present study appears to be too small to impact significantly upon clinical
      assessment of retinal function.

PMID- 20148285
TI  - Fatal herpetic encephalitis during brain radiotherapy in a cerebral metastasized
      breast cancer patient.
AB  - Herpes simplex encephalitis (HSE) is a life-threatening condition with high
      mortality. The pathogenesis underlying the reactivation of latent herpes simplex
      virus (HSV) remains undefined. We present the case of a 55-year-old female who
      developed HSE type 1 during brain irradiation and antioedematous dexamethasone
      treatment for leptomeningeal metastasized breast tumor with epileptic seizures.
      During the radiotherapy (RT), after a total of 32 Gray administrated in 16
      fractions, our patient developed cognitive impairment and partial epileptic
      status without fever. Two days later the patient's clinical conditions had
      deteriorated and high fever manifested. A diagnosis of HSE type 1 was made by a
      positive cerebrospinal fluid polymerase chain reaction. Antiviral therapy with
      high doses of acyclovir was practiced for four weeks but the comatose state
      persisted. The patient died 59 days after the last RT fraction. The temporal
      relationship of RT to the occurrence of HSE suggests that cranial irradiation may
      play a role in the reactivation of latent HSV. Although antiviral therapy
      resistance is infrequent in immunocompetent patients, it is one of the main
      problems in immunocompromized patients.

PMID- 20148286
TI  - Consensus model for identification of novel PI3K inhibitors in large chemical
      library.
AB  - Phosphoinositide 3-kinases (PI3Ks) inhibitors have treatment potential for
      cancer, diabetes, cardiovascular disease, chronic inflammation and asthma. A
      consensus model consisting of three base classifiers (AODE, kNN, and SVM) trained
      with 1,283 positive compounds (PI3K inhibitors), 16 negative compounds (PI3K non
      inhibitors) and 64,078 generated putative negatives was developed for predicting
      compounds with PI3K inhibitory activity of IC(50) < or = 10 microM. The consensus
      model has an estimated false positive rate of 0.75%. Nine novel potential
      inhibitors were identified using the consensus model and several of these contain
      structural features that are consistent with those found to be important for PI3K
      inhibitory activities. An advantage of the current model is that it does not
      require knowledge of 3D structural information of the various PI3K isoforms,
      which is not readily available for all isoforms.

PMID- 20148287
TI  - Screening of benzamidine-based thrombin inhibitors via a linear interaction
      energy in continuum electrostatics model.
AB  - A series of 27 benzamidine inhibitors covering a wide range of biological
      activity and chemical diversity was analysed to derive a Linear Interaction
      Energy in Continuum Electrostatics (LIECE) model for analysing the thrombin
      inhibitory activity. The main interactions occurring at the thrombin binding site
      and the preferred binding conformations of inhibitors were explicitly biased by
      including into the LIECE model 10 compounds extracted from X-ray solved thrombin
      inhibitor complexes available from the Protein Data Bank (PDB). Supported by a
      robust statistics (r(2) = 0.698; q(2) = 0.662), the LIECE model was successful in
      predicting the inhibitory activity for about 76% of compounds (r (ext) (2) > or =
      0.600) from a larger external test set encompassing 88 known thrombin inhibitors
      and, more importantly, in retrieving, at high sensitivity and with better
      performance than docking and shape-based methods, active compounds from a
      thrombin combinatorial library of 10240 mimetic chemical products. The herein
      proposed LIECE model has the potential for successfully driving the design of
      novel thrombin inhibitors with benzamidine and/or benzamidine-like chemical
      structure.

PMID- 20148288
TI  - Optimization, equilibrium and kinetics studies on sorption of Acid Blue 9 using
      brown marine algae Turbinaria conoides.
AB  - In the present study, the parameters, temperature, adsorbent dose, contact time,
      adsorbent size and agitation speed were optimized for Acid Blue 9 removal from
      aqueous medium by using response surface methodology (RSM). The optimum
      conditions for maximum removal of Acid Blue 9 from an aqueous solution of 100
      mg/l were found as follows: temperature (33 degrees C), adsorbent dose (3 g/l),
      contact time (225 min), adsorbent size (85 mesh (0.177 mm)) and agitation speed
      (226 rpm). At these optimized conditions, batch adsorption experiments were
      conducted to study the effect of pH and initial dye concentration for the removal
      Acid Blue 9 dye. Kinetic and equilibrium studies were carried out for the
      experimental results. From the kinetic studies it was found that pseudo second
      order model suits the system well. From the equilibrium studies, the Freundlich
      and Redlich-Peterson isotherm fit the data well.

PMID- 20148289
TI  - A successful implementation of e-epidemiology: the Danish pregnancy planning
      study 'Snart-Gravid'.
AB  - The attraction of being able to use the internet for the recruitment of an
      epidemiologic cohort stems mainly from cost efficiency and convenience. The
      pregnancy planning study ('Snart-Gravid')-a prospective cohort study of Danish
      women planning a pregnancy-was conducted to evaluate the feasibility and cost
      efficiency of using internet-based recruitment and follow-up. Feasibility was
      assessed by examining patient accrual data over time, questionnaire-specific
      response rates and losses to follow-up. The relative cost efficiency was examined
      by comparing the study costs with those of an alternative non internet-based
      study approach. The target recruitment of 2,500 participants over 6 months was
      achieved using advertisements on a health-related website, supported by a
      coordinated media strategy at study initiation. Questionnaire cycle-specific
      response rates ranged from 87 to 90% over the 12-month follow-up. At 6 months,
      87% of women had a known outcome or were still under follow-up; at 12 months the
      figure was 82%. The study cost of $400,000 ($160 per enrolled subject) compared
      favorably with the estimated cost to conduct the same study using a conventional
      non-internet based approach ($322 per subject). The gain in efficiency with the
      internet-based approach appeared to be even more substantial with longer follow
      up and larger study sizes. The successful conduct of this pilot study suggests
      that the internet may be a useful tool to recruit and follow subjects in
      prospective cohort studies.

PMID- 20148290
TI  - Wear testing of a DJOA finger prosthesis in vitro.
AB  - Although the market for replacement of diseased metacarpophalangeal (MCP) joints
      is dominated by single-piece silicone prostheses, several two-piece designs have
      been implanted. One such is the Digital Joint Operative Arthroplasty (DJOA) which
      consists of a part-spherical stainless steel metacarpal component which
      articulates within a matching concave phalangeal component made of ultra high
      molecular weight polyethylene (UHMWPE). A DJOA MCP prosthesis was tested using a
      clinically-validated finger simulator while a second DJOA prosthesis acted as a
      statically-loaded soak-control. Testing ran to 7.1 million cycles of flexion
      extension. It was found that the UHMWPE components, both test and control, gained
      in weight by a similar amount. Therefore apparently there was no wear of the test
      components. However, the initial and final surface finish values of the test
      stainless steel metacarpal head were relatively high. Calculations based on this
      roughness data, plus recent dynamically-loaded soak data, may explain the
      apparent lack of wear.

PMID- 20148291
TI  - Basolateral efflux mediated by multidrug resistance-associated protein 3
      (Mrp3/Abcc3) facilitates intestinal absorption of folates in mouse.
AB  - PURPOSE: This study investigated the role of an ABC transporter, Mrp3/Abcc3 in
      intestinal folate absorption. METHODS: Plasma concentrations of folic acid and
      leucovorin, given orally, were determined in wild-type and Mrp3 ( -/- ) mice.
      Mucosal-to-serosal transport was determined in the everted intestinal sacs. The
      plasma concentrations of endogenous 5-methyltetrahydrofolic acid, homocysteine
      and vitamin B(12), and mRNA levels of hepatic and intestinal folate metabolizing
      enzymes were compared between wild-type and Mrp3 ( -/- ) mice. RESULTS: C ( max )
      and area-under plasma concentration-time curve of folic acid were 3.0- and 2.3
      fold lower in Mrp3 ( -/- ) mice compared with wild-type mice, whereas the total
      body clearance was unchanged. Absorption of leucovorin was significantly delayed
      in Mrp3 ( -/- ) mice. Mucosal-to-serosal transport of folic acid and leucovorin
      was significantly decreased in the duodenum of Mrp3 ( -/- ) mice, where their PS
      ( serosal ) was decreased to 6.3 and 22% of that in wild-type mice, respectively.
      PS ( serosal ) of 5-methyltetrahydrofolic acid was moderately decreased in Mrp3 (
      -/- ) mice. There was no obvious abnormality in folate homeostasis in Mrp3 ( -/-
      ) mice. CONCLUSIONS: Mrp3 accounts for the serosal efflux of folic acid and
      leucovorin, while it makes a moderate contribution to the serosal efflux of 5
      methyltetrahydrofolic acid in mice. Mrp3 dysfunction does not disrupt folate
      homeostasis in mouse.

PMID- 20148293
TI  - Effect of short-term gravitational unloading on rat and mongolian gerbil muscles.
AB  - Gravitational unloading leads to destructive changes in the structure and
      function of muscle fibers. However, the role of the EMG activity level is still
      unclear. We measured changes caused by one- and three-day hypogravity in the
      following muscles: Soleus (Sol), Tibialis anterior (TA) and Gastrocnemius c.m.
      (MG). We used Wistar rats and Mongolian gerbils. The following parameters were
      assessed: the specific force of contraction of isolated fibers by tensometry, the
      transverse stiffness of the contractile apparatus by atomic force microscopy, and
      the calcium content by Fluo-4. We detected the accumulation of calcium ions in
      all muscles even after one-day unloading. In Sol this effect was more significant
      than in other muscles. After one-day of hypogravity we detected an increase in
      the specific force in all muscle types and species. Meanwhile, the transverse
      stiffness of the contractile apparatus, M-band and Z-disc increased only in fast
      muscles but not in Sol. After three-days of unloading, the specific force in Sol
      decreased, and the transverse stiffness of the contractile apparatus behaved in
      the same way as the force. The specific tension of fast muscle fibers decreased
      significantly in comparison with one-day unloading. In addition, the transverse
      stiffness of some areas of MG had a tendency to decrease in comparison to "one
      day" unloading, although there was no such a tendency in the fibers of TA. In
      Mongolian gerbils the tendencies were the same as in the rats, but showed less
      dramatic changes. The reduction in the magnitude of changes in the Sol-MG-TA
      series correlates with EMG activity.

PMID- 20148292
TI  - Formulation and in vitro-in vivo evaluation of black raspberry extract-loaded
      PLGA/PLA injectable millicylindrical implants for sustained delivery of
      chemopreventive anthocyanins.
AB  - PURPOSE: The objective of this study was to formulate and evaluate freeze-dried
      black raspberry (FBR) ethanol extract (RE) loaded poly(DL-lactic-co-glycolic
      acid) (PLGA) and poly(DL-lactic acid) (PLA) injectable millicylindrical implants
      for sustained delivery of chemopreventive FBR anthocyanins (cyanidin-3
      sambubioside (CS), cyanidin-3-glucoside (CG) and cyanidin-3-rutinoside (CR)).
      METHODS: Identification and quantitation of CS, CG, and CR in RE was performed by
      mass spectroscopy and HPLC. RE:triacetyl-beta-cyclodextrin (TA-beta-CD) inclusion
      complex (IC) was prepared by a kneading method and characterized by X-ray
      diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR) and UV-visible
      spectroscopy. RE or RE:TA-beta-CD IC-loaded PLGA or PLA implants were prepared by
      a solvent extrusion method. In vitro and in vivo controlled release studies were
      conducted in phosphate-buffered saline Tween-80 (pH 7.4, 37 degrees C) and after
      subcutaneous administration in male Sprague-Dawley rats, respectively.
      Anthocyanins were quantified by HPLC at 520 nm. RESULTS: The content of CS, CG,
      and CR in RE was 0.2, 1.5, and 3.5 wt%, respectively. The chemical stability of
      anthocyanins in solution was determined to be pH-dependent, and their degradation
      rate increased with an increase in pH from 2.4 to 7.4. PLGA/PLA millicylindrical
      implants loaded with 5 or 10 wt% RE exhibited a high initial burst and short
      release duration of anthocyanins (35-52 and 80-100% CG + CR release after 1 and
      14 days, respectively). The cause for rapid anthocyanins release was linked to
      higher polymer water uptake and porosity associated with the high osmolytic
      components of large non-anthocyanin fraction of RE. XRD, (1)H NMR and UV-visible
      spectroscopy indicated that the non-anthocyanin fraction molecules of RE formed
      an IC with TA-beta-CD, decreasing the hydrophilicity of RE. Formation of an IC
      with hydrophobic carrier, TA-beta-CD, provided better in vitro/in vivo sustained
      release of FBR anthocyanins (16-24 and 97-99% CG + CR release, respectively,
      after 1 and 28 days from 20 wt% RE:TA-beta-CD IC/PLA implants) over 1 month,
      owing to reduced polymer water uptake and porosity. CONCLUSION: PLA injectable
      millicylindrical implants loaded with RE:TA-beta-CD IC are optimal dosage forms
      for 1-month slow and continuous delivery of chemopreventive FBR anthocyanins.

PMID- 20148294
TI  - Epigenetics in mammary gland biology and cancer.

PMID- 20148296
TI  - Multi-informant predictors of social inclusion for students with autism spectrum
      disorders attending mainstream school.
AB  - This study examined differential profiles of behavioural characteristics
      predictive of successful inclusion in mainstream education for children with
      autism spectrum disorders (ASD) and comparison students. Multiple regression
      analyses using behavioural ratings from parents, teachers and peers found some
      evidence for differential profiles predicting peer acceptance and rejection. High
      levels of peer-rated shyness significantly predicted social rejection in
      comparison students only. Parent-rated prosocial behaviour also differentially
      predicted social acceptance; high-levels of prosocial behaviour predicted
      acceptance in comparison students, but low-levels were predictive for students
      with ASD. These findings suggest that schools may seek to augment traditional
      social skills programmes with awareness raising about ASD among mainstream pupils
      to utilise peers' apparent willingness to discount characteristics such as
      'shyness'.

PMID- 20148295
TI  - Accelerated formation of alpha-synuclein oligomers by concerted action of the 20S
      proteasome and familial Parkinson mutations.
AB  - A hallmark of Parkinson disease (PD) is the formation of intracellular protein
      inclusions called Lewy bodies that also contain mitochondria. alpha-Synuclein
      (alpha Syn) is a major protein component of Lewy bodies, where it is in an
      amyloid conformation and a significant fraction is truncated by poorly understood
      proteolytic events. Previously, we demonstrated that the 20S proteasome cleaves
      alpha Syn in vitro to produce fragments like those observed in Lewy bodies and
      that the fragments accelerate the formation of amyloid fibrils from full-length
      alpha Syn. Three point mutations in alpha Syn are associated with early-onset
      familial PD: A30P, E46K, and A53T. However, these mutations have very different
      effects on the amyloidogenicity and vesicle-binding activity of alpha Syn,
      suggesting neither of these processes directly correlate with neurodegeneration.
      Here, we evaluate the effect of the disease-associated mutations on the
      fragmentation, conformation, and association reactions of alpha Syn in the
      presence of the 20S proteasome and liposomes. The 20S proteasome produced the C
      terminal fragments from both the mutant and wildtype alpha Syn. These truncations
      accelerated fibrillization of all alpha-synucleins, but again there was no clear
      correlation between the PD-associated mutations and amyloid formation in the
      presence of liposomes. Recent data suggests that cellular toxicity is caused by a
      soluble oligomeric species, which is a precursor to the amyloid form and is
      immunologically distinguishable from both soluble monomeric and amyloid forms of
      alpha Syn. Notably, the rate of formation of the soluble, presumptively cytotoxic
      oligomers correlated with the disease-associated mutations when both 20S
      proteasome and liposomes were present. Under these conditions, the wildtype
      protein was also cleaved and formed the oligomeric structures, albeit at a slower
      rate, suggesting that 20S-mediated truncation of alpha Syn may play a role in
      sporadic PD as well. Evaluation of the biochemical reactions of the PD-associated
      alpha-synuclein mutants in our in vitro system provides insight into the possible
      pathogenetic mechanism of both familial and sporadic PD.

PMID- 20148297
TI  - A report on the journal.

PMID- 20148298
TI  - Definitions of empirically supported treatment.

PMID- 20148299
TI  - Improved diagnostic validity of the ADOS revised algorithms: a replication study
      in an independent sample.
AB  - Recently, Gotham et al. (2007) proposed revised algorithms for the Autism
      Diagnostic Observation Schedule (ADOS) with improved diagnostic validity. The aim
      of the current study was to replicate predictive validity, factor structure, and
      correlations with age and verbal and nonverbal IQ of the ADOS revised algorithms
      for Modules 1 and 2 in a large independent Dutch sample (N = 532). Results showed
      that the improvement of diagnostic validity was most apparent for autism, except
      in very young or low functioning children. Results for other autism spectrum
      disorders were less consistent. Overall, these findings support the use of the
      more homogeneous revised algorithms, with the use of similar items across
      developmental cells making it easier to compare ADOS scores within and between
      individuals.

PMID- 20148300
TI  - Novel recombinant norovirus in Japan.
AB  - Based on the genetic analysis, novel, naturally occurring recombinant norovirus
      strains were identified in Japan. Breakpoint analysis of recombinant norovirus
      showed that the recombination site was at the open reading frame ORF1/ORF2
      overlap.

PMID- 20148301
TI  - Molecular analysis of the virulence attenuation process in Junin virus vaccine
      genealogy.
AB  - The Junin virus strain Candid#1 was developed as a live attenuated vaccine for
      Argentine hemorrhagic fever. In this article, we report sequence information of
      the L and S RNAs of Junin virus Candid#1 and XJ#44 strains, and show the
      comparisons with the XJ13 wild-type strain and with other Junin virus strains,
      like Romero, IV4454 and MC2 strains, and other closely and distantly related
      arenaviruses. Comparisons of the nucleotide and amino acid sequences of all genes
      of three strains from the same vaccine genealogy, revealed different point
      mutations that could be associated with the attenuated phenotype. A 91% of the
      mutations found are consistent with a hypothesis of progressive attenuation of
      virulence from XJ13 to XJ#44 and to Candid#1; 39% of mutations were observed in
      XJ#44 and conserved in Candid#1, while another 52% of the mutations appeared only
      in Candid#1 strain. The remaining 9% corresponded to reverse mutations in the L
      gene. In summary, the present work shows a set of mutations that could be related
      to the virulence attenuation phenomenon. This information will serve as a
      starting point to study this biological phenomenon, provided that a reverse
      genetics system for Junin virus is developed to allow the generation of
      infectious virions with specific mutations.

PMID- 20148302
TI  - Samples and systems: finding the fit to improve care for adolescent depression.

PMID- 20148303
TI  - Relational aggression and hostile attribution biases: testing multiple
      statistical methods and models.
AB  - The present study used both categorical and dimensional approaches to test the
      association between relational and physical aggression and hostile intent
      attributions for both relational and instrumental provocation situations using
      the National Institute of Child Health and Human Development longitudinal Study
      of Early Child Care and Youth Development (M = 8.3 years-old, SD = 0.19, N =
      840). A one standard deviation threshold was used to create categorical
      aggression status groups. In categorical analyses, children who were both
      relationally and physically aggressive were found to attribute more hostile
      intent attributions in relationally provocative situations. Results from the
      dimensional analyses indicated that female gender, physical aggression, and
      hostile attribution biases for instrumental provocations each predicted increases
      in relational aggression over time. Further, relational aggression was not
      predictive of hostile attribution biases for relational provocations, and instead
      physical aggression was predictive. Implications for the fields of developmental
      psychology and psychopathology are discussed.

PMID- 20148304
TI  - Effect of chronic lead exposure on pro-apoptotic Bax and anti-apoptotic Bcl-2
      protein expression in rat hippocampus in vivo.
AB  - Despite reduction in environmental lead, chronic lead exposure still possess a
      public health hazard, particularly in children, with devastating effects on
      developing CNS. To investigate the mechanism of this neurotoxicity, young and
      adult rats were used to study whether exposure to 500 ppm concentrations of lead
      could induce apoptosis in hippocampus. 2-4 and 12-14-week-old rats received lead
      acetate in concentration of 500 ppm for 40 days. Control animals received
      deionized distilled water. In lead-treated groups, the blood lead levels were
      increased by 3-4 folds. Light and electron microscopical study of hippocampus
      revealed increased apoptotic cells. Western blot analysis of Bax and Bcl-2 (pro-
      and anti-apoptotic gene products, respectively) indicated higher expression of
      Bax protein and no significant change in bcl-2 expression and accordingly
      increased the Bax/Bcl-2 ratio compared to control group, confirming the
      histological study. In conclusion, these data suggest that neurotoxicity of
      chronic lead exposure in hippocampus in vivo may partly be due to facilitation of
      apoptosis.

PMID- 20148305
TI  - Probiotic Lactobacillus casei expressing human lactoferrin elevates antibacterial
      activity in the gastrointestinal tract.
AB  - In this study, Lactobacillus casei was used to deliver and express human
      lactoferrin (hLF) to protect the host against bacterial infection. Full-length
      hLF cDNA was cloned into a Lactobacillus-specific plasmid to produce the L. casei
      transformants (rhLF/L. casei). Antimicrobial activity of recombinant hLF was
      examined in inhibition of bacteria growth in vitro. A mouse model was established
      to test in vivo antibacterial activity and protective effect of orally
      administered probiotic L. casei transformant in the gastrointestinal tract.
      Trials were conducted in which animals were challenged with E. coli ATCC25922. E.
      coli colony numbers in duodenal fluid from the group fed with rhLF/L. casei were
      significantly lower than those of the group fed with wild-type L. casei or
      placebo (P < 0.01). Histopathological analyses of the small intestine, showed
      both decreased intestinal injury and increased villi length were observed in the
      mice fed with rhLF/L. casei as compared with the control groups (P < 0.01). Our
      results demonstrate that L. casei expressing hLF exhibited antibacterial activity
      both in in vitro and in vivo. It also provides a potentially large-scale
      production of hLF as applications for treatment of infections caused by
      clinically relevant pathogens.

PMID- 20148306
TI  - Effect of dietary L-tryptophan on osmotic stress tolerance in common carp,
      Cyprinus carpio, juveniles.
AB  - Common carp juveniles were fed two types of diet (control: 0.1% tryptophan and
      TRP: 0.6% tryptophan) over 15 days. Thereafter, both groups were directly
      subjected to osmotic challenge (from 0 to 10 ppt) for 168 h. Blood samples were
      collected at -240, 0, 6, 24, 72 and 168 h after challenge. Survival and serum
      cortisol, glucose, sodium and chloride levels were measured to determine stress
      response and osmoregulation condition. While TRP group showed no mortality until
      168 h, cumulative mortality was near 100% at 72 h after challenge in control
      group. Feeding tryptophan-supplemented diet led to increase in prechallenge
      cortisol, but not glucose, sodium and chloride values at -240 h that stayed
      elevated until 0 h after challenge. After challenge, cortisol and glucose values
      did not significantly affected by time of sampling but type of diet and diet*time
      interaction. Sodium values significantly affected by diet type and time of
      sampling but not their interaction. Chloride values significantly affected by
      time of sampling but not diet type and their interaction. Control group had
      higher cortisol, glucose and sodium than TRP at each time of sampling. Control
      and TRP group showed increasing and decreasing pattern in cortisol and glucose
      values when experiment progressed after osmotic challenge. Both group showed
      increasing pattern in sodium and chloride values when experiment progressed after
      osmotic challenge. Results indicated that tryptophan supplementation enhanced
      salt water tolerance of carp that is due to increase in basal cortisol and anti
      stress effect of tryptophan and possibly increase in serotonergic activity.

PMID- 20148307
TI  - Withdrawal from fixed-dose injection of methamphetamine decreases cerebral levels
      of 3-methoxy-4-hydroxyphenylglycol and induces the expression of anxiety-related
      behavior in mice.
AB  - A variety of drug treatment regimens have been proposed to model the dysphoric
      state observed during methamphetamine (METH) withdrawal in rats, but little has
      been established in experiments using mice. In male ICR mice, a fixed-dose
      injection regimen of METH (1.0 or 2.5 mg/kg, i.p., twice daily for 10 consecutive
      days) induced a significant decrease in the time spent in open arms in an
      elevated plus maze after 5 days of drug abstinence. Under an escalating-dose
      injection regimen (0.2-2.0 mg/kg, i.p., 3 times daily for 4 days, total: 15
      mg/kg/animal) or continuous subcutaneous administration with osmotic mini-pumps
      (15 or 76 mg/kg of METH for 2 weeks), no significant behavioral change was
      observed after 5 days of drug abstinence, compared with control animals. Reduced
      gains in body weight were observed during repeated treatment with METH in the
      fixed-dose injection and mini-pump treatment regimens, but not the escalating
      dose injection regimen. HPLC analysis revealed significant decreases in the level
      of cerebral 3-methoxy-4-hydroxyphenylglycol, a norepinephrine metabolite, and
      norepinephrine turnover, which may be attributed to the expression of anxiety
      related behavior in the elevated plus maze. These observations suggest that the
      mice treated with a fixed-dose of METH may model the anxiety-related behavior
      observed in the dysphoric state induced by METH withdrawal in humans.

PMID- 20148308
TI  - In vitro angioplasty of atherosclerotic human femoral arteries: analysis of the
      geometrical changes in the individual tissues using MRI and image processing.
AB  - Existing atherosclerotic plaque imaging techniques such as intravascular
      ultrasound, multidetector computed tomography, optical coherence tomography, and
      high-resolution magnetic resonance imaging (hrMRI) require computerized methods
      to separate and analyze the plaque morphology. In this work, we perform in vitro
      balloon angioplasty experiments with 10 human femoral arteries using hrMRI and
      image processing. The vessel segments contain low-grade to high-grade lesions
      with very different plaque compositions. The experiments are designed to mimic
      the in vivo situation. We use a semi-automatic image processing tool to extract
      the three-dimensional (3D) geometries of the tissue components at four
      characteristic stages of the angioplasty procedure. The obtained geometries are
      then used to determine geometrical and mechanical indices in order to
      characterize, classify, and analyze the atherosclerotic plaques by their specific
      geometrical changes. During inflation, three vessels ruptured via helical crack
      propagation. The adventitia, media, and intima did not preserve their area/volume
      during inflation; the area changes of the lipid pool during inflation were
      significant. The characterization of changes in individual 3D tissue geometries,
      together with tissue-specific mechanical properties, may serve as a basis for
      refined finite element (FE) modeling, which is key to better understand stress
      evolution in various atherosclerotic plaque configurations.

PMID- 20148310
TI  - The lemniscal and paralemniscal pathways of the trigeminal system in rodents are
      integrated at the level of the somatosensory cortex.
AB  - The studies reported here demonstrate that the projection representation of the
      whiskers in the somatosensory cortex in rats is the area at which afferent
      streams arriving via the lemniscal and paralemniscal projections interact. The
      responses of neurons in layers IV, Va, and Vb to mechanical stimulation of single
      whiskers were studied. Neurons in layers IV and Vb were found to show more
      frequent phasic responses (typical of the lemniscal system), while those in layer
      Va produced predominantly tonic responses (typical of the paralemniscal system).
      These characteristics of adaptive-plastic rearrangements of cortical neuron
      activity in response to constant stimuli may result from intracortical
      cooperative interactions between the lemniscal and paralemniscal projection
      systems, which, overall, produces a precise qualitative assessment of the
      perceived stimulus in its specific context.

PMID- 20148311
TI  - Women's reproductive health in slum populations in India: evidence from NFHS-3.
AB  - The urban population in India is one of the largest in the world. Its
      unprecedented growth has resulted in a large section of the population living in
      abject poverty in overcrowded slums. There have been limited efforts to capture
      the health of people in urban slums. In the present study, we have used data
      collected during the National Family Health Survey-3 to provide a national
      representation of women's reproductive health in the slum population in India. We
      examined a sample of 4,827 women in the age group of 15-49 years to assess the
      association of the variable slum with selected reproductive health services. We
      have also tried to identify the sociodemographic factors that influence the
      utilization of these services among women in the slum communities. All analyses
      were stratified by slum/non-slum residence, and multivariate logistic regression
      was used to analyze the strength of association between key reproductive health
      services and relevant sociodemographic factors. We found that less than half of
      the women from the slum areas were currently using any contraceptive methods, and
      discontinuation rate was higher among these women. Sterilization was the most
      common method of contraception (25%). Use of contraceptives depended on the age,
      level of education, parity, and the knowledge of contraceptive methods (p <
      0.05). There were significant differences in the two populations based on the
      timing and frequency of antenatal visits. The probability of ANC visits depended
      significantly on the level of education and economic status (p < 0.05). We found
      that among slum women, the proportion of deliveries conducted by skilled
      attendants was low, and the percentage of home deliveries was high. The use of
      skilled delivery care was found to be significantly associated with age, level of
      education, economic status, parity, and prior antenatal visits (p < 0.05). We
      found that women from slum areas depended on the government facilities for
      reproductive health services. Our findings suggest that significant differences
      in reproductive health outcomes exist among women from slum and non-slum
      communities in India. Efforts to progress towards the health MDGs and other
      national or international health targets may not be achieved without a focus on
      the urban slum population.

PMID- 20148312
TI  - Ataxin active site determination using spectral distribution of electron ion
      interaction potentials of amino acids.
AB  - Ataxia is a genetic neurological disorder characterised by a neurodegenerative
      process affecting a motor cortex responsible for balance and coordination.
      Recently several genes that cause autosomal dominant ataxia development were
      identified. These abnormal genes share a common ability to produce abnormal
      ataxin proteins that can affect nerve cells in the cerebellum and spinal cord.
      Here, using the Resonant Recognition Model (RRM) based on signal processing, we
      analysed ataxin proteins and identified the characteristic features corresponding
      to their biological activities. The RRM is a physico-mathematical model developed
      for analysis of protein interactions. By incorporating Smoothed Pseudo Wigner
      Ville distribution (SPWV) in the RRM, we can define the active regions along the
      protein molecule. The results showed that our computational predictions
      correspond closely with the experimentally identified locations of the
      active/binding sites for ataxin-1 and ataxin-3 protein groups. The results
      obtained provide a valuable insight into the functional performance of ataxin
      proteins.

PMID- 20148313
TI  - Model predictive control of relative blood volume and heart rate during
      hemodialysis.
AB  - To maintain the hemodynamic stability of patient undergoing hemodialysis, this
      article proposes a novel model-based control methodology to regulate the changes
      in relative blood volume (RBV) and percentage change in heart rate (DeltaHR(%))
      during hemodialysis by adjusting the ultrafiltration rate (UFR). The control
      algorithm uses model predictive control (MPC) to account for system variability
      and to explicitly handle the constraints on UFR. Linear state-space system with
      time-varying parameters is introduced to model the RBV and DeltaHR. MPC was used
      to track the change in RBV and DeltaHR to pre-defined reference trajectories. At
      each sampling instant, the system parameters are updated to get the best fitting
      into the parameterized model. Simulation results demonstrate that the system is
      able to regulate RBV and DeltaHR to the reference by adjusting UFR while keeping
      it within practically realizable bounds. The results show that adjusting UFR may
      improve the stability of patient during dialysis when compared to conventional
      hemodialysis with constant UFR.

PMID- 20148314
TI  - Comparison of pre-treatment clinical prognostic factors in patients with gastro
      oesophageal cancer and proposal of a new staging system.
AB  - BACKGROUND: Clinical staging in patients with gastro-oesophageal cancer, is of
      crucial importance in determining the likely benefit of treatment. Despite recent
      advances in clinical staging, overall survival remains poor. The aim of the
      present study was to examine the relationship between pre-treatment clinical
      prognostic factors and cancer-specific survival. METHODS: Two hundred and
      seventeen patients, undergoing staging investigations including host factors
      (Edinburgh Clinical Risk Score (ECRS)) and the systemic inflammatory response
      (Glasgow Prognostic score (mGPS)), in the upper GI surgical unit at Glasgow Royal
      Infirmary, were studied. RESULTS: During the follow-up period, 188 (87%) patients
      died; 178 of these patients died from the disease. The minimum follow-up was 46
      months, and the median follow-up of the survivors was 65 months. On multivariate
      survival analysis of the significant factors, only cTNM stage (HR 1.84, 95% CI
      1.56-2.17, p < 0.001), mGPS (HR 1.67, 95% CI 1.35-2.07, p < 0.001) and treatment
      (HR 2.12, 95% CI 1.73-2.60, p < 0.001) were independently associated with
      survival. An elevated mGPS was associated with advanced cTNM stage, poor
      performance status, an elevated ECRS and more conservative treatment.
      CONCLUSIONS: Pre-treatment mGPS improves clinical staging in patients with gastro
      oesophageal cancer. Therefore, it is likely to aid clinical decision making for
      these difficult to treat patients.

PMID- 20148315
TI  - Protection by D609 through cell-cycle regulation after stroke.
AB  - Expressions of cell-cycle regulating proteins are altered after stroke. Cell
      cycle inhibition has shown dramatic reduction in infarction after stroke.
      Ceramide can induce cell-cycle arrest by up-regulation of cyclin-dependent kinase
      (Cdk) inhibitors p21 and p27 through activation of protein phosphatase 2A (PP2A).
      Tricyclodecan-9-yl-xanthogenate (D609)-increased ceramide levels after transient
      middle cerebral artery occlusion (tMCAO) in spontaneously hypertensive rat (SHR)
      probably by inhibiting sphingomyelin synthase (SMS). D609 significantly reduced
      cerebral infarction and up-regulated Cdk inhibitor p21 and down-regulated phospho
      retinoblastoma (pRb) expression after tMCAO in rat. Others have suggested bFGF
      induced astrocyte proliferation is attenuated by D609 due to an increase in
      ceramide by SMS inhibition. D609 also reduced the formation of oxidized
      phosphatidylcholine (OxPC) protein adducts. D609 may attenuate generation of
      reactive oxygen species and formation of OxPC by inhibiting microglia/macrophage
      proliferation after tMCAO (please also see note added in proof: D609 may prevent
      mature neurons from entering the cell cycle at the early reperfusion, however may
      not interfere with later proliferation of microglia/ macrophages that are the
      source of brain derived neurotrophic factor (BDNF) and insulin-like growth factor
      (IGF-1) in offering protection). It has been proposed that D609 provides benefit
      after tMCAO by attenuating hypoxia-inducible factor-1alpha and Bcl2/adenovirus
      E1B 19 kDa interacting protein 3 expressions. Our data suggest that D609 provides
      benefit after stoke through inhibition of SMS, increased ceramide levels, and
      induction of cell-cycle arrest by up-regulating p21 and causing
      hypophosphorylation of Rb (through increased protein phosphatase activity and/or
      Cdk inhibition).

PMID- 20148316
TI  - Astrogliosis in CNS pathologies: is there a role for microglia?
AB  - Astrogliosis, a cellular reaction with specific structural and functional
      characteristics, represents a remarkably homotypic response of astrocytes to all
      kinds of central nervous system (CNS) pathologies. Astrocytes play diverse
      functions in the brain, both harmful and beneficial. Mounting evidence indicates
      that astrogliosis is an underlying component of a diverse range of diseases and
      associated neuropathologies. The mechanisms that lead to astrogliosis are not
      fully understood, nevertheless, damaged neurons have long been reported to induce
      astrogliosis and astrogliosis has been used as an index for underlying neuronal
      damage. As the predominant source of proinflammatory factors in the CNS,
      microglia are readily activated under certain pathological conditions. An
      increasing body of evidence suggests that release of cytokines and other soluble
      products by activated microglia can significantly influence the subsequent
      development of astrogliosis and scar formation in CNS. It is well known that
      damaged neurons activate microglia very quickly, therefore, it is possible that
      activated microglia contribute factors/mediators through which damaged neuron
      induce astrogliosis. The hypothesis that activated microglia initiate and
      maintain astrogliosis suggests that suppression of microglial overactivation
      might effectively attenuate reactive astrogliosis. Development of targeted anti
      microglial activation therapies might slow or halt the progression of
      astrogliosis and, therefore, help achieve a more beneficial environment in
      various CNS pathologies.

PMID- 20148317
TI  - ATP dependent chromatin remodeling enzymes in embryonic stem cells.
AB  - Embryonic stem (ES) cells are pluripotent cells that can self renew or be induced
      to differentiate into multiple cell lineages, and thus have the potential to be
      utilized in regenerative medicine. Key pluripotency specific factors (Oct
      4/Sox2/Nanog/Klf4) maintain the pluripotent state by activating expression of
      pluripotency specific genes and by inhibiting the expression of developmental
      regulators. Pluripotent ES cells are distinguished from differentiated cells by a
      specialized chromatin state that is required to epigenetically regulate the ES
      cell phenotype. Recent studies show that in addition to pluripotency specific
      factors, chromatin remodeling enzymes play an important role in regulating ES
      cell chromatin and the capacity to self-renew and to differentiate. Here we
      review recent studies that delineate the role of ATP dependent chromatin
      remodeling enzymes in regulating ES cell chromatin structure.

PMID- 20148319
TI  - Mechanisms supporting transfer of inhibitory signals into the spike output of
      spontaneously firing cerebellar nuclear neurons in vitro.
AB  - Cerebellar cortical signals are carried to their principal target, the deep
      cerebellar nuclear neurons (DCNs), via the inhibitory pathway formed by Purkinje
      cell (PC) axons. Two different intrinsic properties of DCNs, rebound excitation
      and automatic firing, have been proposed to support ensuing mechanisms for
      information transfer via inhibitory synapses. The efficacy of these mechanisms
      was investigated using whole-cell recordings of spontaneously firing DCNs in
      cerebellar slices. Results using current injection revealed that both mechanisms
      are effective in spontaneously firing DCNs but operate at different ranges of
      membrane potential. Rebound frequency was well correlated to the duration and
      amplitude of the preceding hyperpolarization. Activation of PC synapses with
      trains of stimuli few seconds long elicited rebound firing in all tested neurons,
      demonstrating that inhibition can elicit rebounds in DCNs held at their
      spontaneous membrane potential. Rebounds could be also elicited by single
      stimulus in a subset of neurons. The rebound frequency was significantly
      correlated to the synaptic stimulus strength, supporting the idea that rebound
      frequency may encode the amplitude of inhibition and thus serve to transfer
      inhibitory signals in the cerebellar circuit.

PMID- 20148318
TI  - Cytoskeletal disassembly and cell rounding promotes adipogenesis from ES cells.
AB  - Biomechanical signals such as cell shape and spreading play an important role in
      controlling stem cell commitment. Cell shape, adhesion and spreading are also
      affected by calreticulin, a multifunctional calcium-binding protein, which
      influences several cellular processes, including adipogenesis. Here we show that
      cytoskeletal disruption in mouse embryonic stem cells using cytochalasin D or
      nocodazole promotes adipogenesis. While cytochalasin D disrupts stress fibres and
      inhibits focal adhesion formation, nocodazole depolymerises microtubules and
      promotes focal adhesion formation. Furthermore, cytochalasin D increases the
      levels of both total and activated calcium/calmodulin-dependent protein kinase
      II, whereas nocodazole decreases it. Nevertheless, both treatments significantly
      increase the adipogenic potential of embryonic stem cells in vitro. Both
      cytochalasin D and nocodazole exposure caused cell rounding suggesting that it is
      cell shape that causes the switch towards the adipogenic programme. Calreticulin
      containing embryonic stem cells, under baseline conditions, show low adipogenic
      potential, have low activity of signalling via calcium/calmodulin-dependent
      protein kinase II and display normal adhesive properties and cellular spreading
      in comparison to the highly adipogenic but poorly spread calreticulin-deficient
      ES cells. We conclude that forced cell rounding via cytoskeletal disruption
      overrides the effects of calreticulin, an ER chaperone, thus negatively
      regulating adipogenesis via focal adhesion-mediated cell spreading.

PMID- 20148320
TI  - Chest compressions versus ventilation plus chest compressions in a pediatric
      asphyxial cardiac arrest animal model.
AB  - OBJECTIVE: To compare the ventilation achieved with chest compressions (CC) or
      ventilation plus compressions (VC) in a pediatric animal model of cardiac arrest.
      DESIGN: Randomized experimental study. SETTING: Experimental department of a
      University Hospital. METHODS: Twelve infant pigs with asphyxial cardiac arrest.
      Sequential 3-min periods of VC and CC were performed for a total duration of 9
      min. Tidal volume (TV), end-tidal CO(2) (EtCO(2)), mean arterial pressure (MAP),
      central venous pressure (CVP), mean pulmonary arterial pressure (mPAP), and
      peripheral, cerebral, and renal saturations were recorded and arterial and venous
      blood gases were analyzed. RESULTS: VC achieved a TV similar to the preset
      parameters on the ventilator, whilst the TV in CC was very low (P < 0.001).
      EtCO(2) with VC was significantly higher than with CC (14.0 vs. 3.9 mmHg, P <
      0.05). Arterial pH was higher with VC than with CC (6.99 vs. 6.90 mmHg, P <
      0.05). Arterial PCO(2) was lower with VC than with CC (62.1 vs. 97.0 mmHg, P <
      0.05). There were no significant differences in the MAP; CVP; mPAP; peripheral,
      renal, and cerebral saturations; or lactate concentrations between the two
      techniques. CONCLUSIONS: VC achieves better ventilation than CC during
      cardiopulmonary resuscitation and has no negative effect on the hemodynamic
      situation.

PMID- 20148321
TI  - Bilevel positive airway pressure ventilation: factors influencing carbon dioxide
      rebreathing.
AB  - PURPOSE: Use of bilevel positive airway pressure (BLPAP) ventilators for
      noninvasive ventilation (NIV) is an established treatment for both acute and
      chronic ventilatory failure. Although BLPAP ventilator circuits are simpler than
      those of conventional ventilators, one drawback to their use is that they allow
      variable amounts of rebreathing to occur. The aim of this work is to measure the
      amount of CO(2) reinsufflated in relation to the BLPAP ventilator circuit in
      patients, and to determine predictive factors for rebreathing. METHODS: Eighteen
      adult patients were ventilated on pressure support, either by intubation or with
      mask ventilation, during a weaning period. The mean inspiratory fraction of CO(2)
      (tidal FiCO(2)) reinsufflated from the circuit between the intentional leak and
      the ventilator was measured for each breath. The influence of end-tidal CO(2)
      concentration (ETCO(2)), respiratory rate (RR), percentage of inspiratory time (T
      (i)/T (TOT)), application of expiratory positive airway pressure (EPAP), and
      inspiratory tidal volume on magnitude of tidal FiCO(2), as well as the influence
      of intubation versus NIV, were studied by univariate comparisons and logistic
      regression analysis. RESULTS: In a total of 11,107 cycles, tidal FiCO(2) was
      0.072 +/- 0.173%. Of fractions measured, 8,976 (81%) were under 0.10% and 2,131
      (19%) were over 0.10%, with mean values of 0.026 +/- 0.027% and 0.239 +/- 0.326%,
      respectively. ETCO(2), EPAP, NIV versus intubation, and RR had significant
      predictive value for tidal FiCO(2) >0.10%. CONCLUSIONS: BLPAP ventilators present
      a specific rebreathing risk to patients. However, that risk remains modest, even
      in intubated patients, provided that EPAP is applied.

PMID- 20148322
TI  - Increasing financial burden of revision total knee arthroplasty.
AB  - We reviewed the peri-operative and financial data of patients who underwent
      revision total knee arthroplasty in our institution between 1997 and 2006. The
      aims were to compare difference in cost between aseptic and septic cases and to
      identify the sources of preventable cost increase in revision knee procedure. The
      study group comprised 117 women (65%) and 62 men (35%). The median age of
      patients decreased from 73 years (37-83 years) in 1997-2001 to 70 years (15-91
      years) in 2002-2006, a decline of 4% (P < 0.05). The mean ASA scores also dropped
      from 3 to 2 between the two periods. Despite this, the mean total cost of
      revision knee procedure continued to increase. Patients undergoing revision
      arthroplasty because of infection had much higher (P = 0.0001) cost compared to
      their aseptic counterpart. Increase in the costs of investigations (P < 0.05) and
      implant (P < 0.05) was the major contributing factors. The cost of implants
      increased by 32-35% (P < 0.05) depending on implant selection. Changing
      demographics will increase the requirement for this surgery and thus increase its
      overall cost to society. Cost increases associated with unnecessary
      investigations, prolonged hospital stay and use of expensive implants should be
      avoided.

PMID- 20148323
TI  - Open wedge valgus tibial osteotomies: affecting the distinct ACL bundles.
AB  - Valgus alignment affects the biomechanical behavior of the ACL, resulting in an
      increase of the in situ forces in the posterolateral (PL) bundle of the graft.
      The amount of valgus alignment creating such effects on the force remains
      unclear. Furthermore, the mechanistic rational for the increase in situ forces on
      the PL bundle when compared with the AM during the valgus osteotomy remained
      unclear. We hypothesized that increasing valgisation of the knee results in
      significantly increased obliquity and a resulting increasing elongation pattern
      and apparent strain of the PL bundle compared to the AM bundle. Six cadaver legs
      were used utilizing two commercial navigation systems including navigated high
      tibial osteotomy (HTO) and ACL measurements simultaneously. ACL footprints were
      registered for the central and identified AM and PL bundle. A stepwise oblique
      open wedge osteotomy was performed for 7.5 degrees  and 15 degrees  valgisation.
      Length changes and coronal plane obliquity were determined at 0 degrees  and 30
      degrees  flexion. The apparent strain for each fiber was calculated. Valgisation
      significantly affects the length and obliquity of the PL portion of ACL.
      Valgisation of 7.5 degrees  appears to be a threshold for affecting PL length and
      obliquity without significant changes compared to 15 degrees . The mean apparent
      strain for the PL bundle increases up to 14% with a 15 degrees  osteotomy in full
      extension, compared to 4% for the central and 2% for the AM bundle. HTO should be
      done prior to fixation the ACL graft in combined procedures as valgisation does
      affect graft length. Relative alignment influence on obliquity and length of the
      PL bundle should be considered in valgus knees.

PMID- 20148324
TI  - A novel standardized algorithm for evaluating patients with painful total knee
      arthroplasty using combined single photon emission tomography and conventional
      computerized tomography.
AB  - SPECT/CT is a promising diagnostic modality in patients with painful total knee
      arthroplasty (TKA). The purpose of this study is to introduce a novel
      standardized SPECT/CT algorithm and evaluate its clinical application and
      reliability. A novel SPECT/CT localization scheme consisting of 9 tibial, 9
      femoral and 4 patellar regions on standardized axial, coronal and sagittal slices
      is proposed. It was piloted in 18 consecutive patients with post TKA pain. The
      tracer activity on SPECT/CT was recorded using a color-coded scale (0-10). The
      inter- and intra-observer reliability was assessed for localization and tracer
      activity. The prosthetic component position was assessed in the CT images after
      3D reconstruction using standardized frames of reference. The median inter- and
      intra-observer differences and ranges of the measured angles were calculated
      along with the ICC values for inter- and intra-observer reliability. The
      localization scheme showed very high inter- and intra-observer reliabilities for
      all regions. The measurement of component position was highly reliable in all
      cases with sufficient visibility of anatomical landmarks. The median inter
      observer difference between alignment measurements for tibial and femoral
      components was less than 3 degrees (range 0 degrees -6 degrees ). The median
      intra-observer variability for these was less than 2 degrees (range 0 degrees -5
      degrees ). The SPECT/CT algorithm presented is both reliable and useful in the
      management of patients with painful TKA. It combines biomechanical and metabolic
      data (tracer localization) providing an extra dimension to the understanding of
      this difficult condition. The clinical value of SPECT/CT in patients with
      unexplained pain following TKA should be further investigated.

PMID- 20148325
TI  - Augmentation technique for partial ACL ruptures using semitendinosus tendon in
      the over-the-top position.
AB  - The aim of this study is to present a surgical augmentation technique for partial
      ACL ruptures in which an isolated, autologous, double-bundle semitendinosus
      tendon graft is passed over the top of the femur, thus fully preserving the still
      intact fibers of the ligament remnant. Between 1992 and 2006, 24 patients
      underwent ACL semitendinosus autograft reconstruction and were followed up for at
      least 2 years. The median follow-up was 6.2 years (2-15.6). At the last follow-up
      examination, the patients were evaluated using the International Knee
      Documentation Committee scale. Subjective and functional parameters were assessed
      using the Tegner activity scale and the Lysholm scale. Instrumental evaluation
      was carried out using the KT-1000 instrument. Sixteen of the 24 patients achieved
      an IKDC score of A. Of the remaining eight patients, six achieved an IKDC score
      of B, one an IKDC score of C, and one an IKDC score of D. According to the Tegner
      activity scale, the median pre-injury sports activity level was seven (5-9) and
      the median post-injury level was six (4-9), while the mean Lysholm scale score
      was 95 (90-100). Clinical and biomechanical studies have shown that
      reconstruction techniques that address both bundles of the ACL provide better
      rotational stability than techniques that address only a single bundle.
      Therefore, it seems logical than in patients with a partial rupture of the ACL,
      the intact bundle could be preserved and only the torn bundle would need to be
      reconstructed.

PMID- 20148326
TI  - Muscle torque in total knee arthroplasty: comparison of subvastus and midvastus
      approaches.
AB  - The subvastus and midvastus approaches are two of the most commonly performed
      quadriceps preserving approaches for total knee arthroplasty (TKA), which can
      hasten functional recovery and rehabilitation. However, there has not been
      sufficient investigation with respect to a quantitative comparison between the
      two approaches in terms of muscle strength. To compare outcomes with respect to
      muscle strength between these two approaches, quadriceps and hamstring muscle
      torques of 20 patients who underwent primary TKA with the subvastus (SV) approach
      and 10 patients who received the midvastus (MV) approach were measured after
      surgery. The median age of patients in the SV group (68 years, range 53-77 years)
      was significantly different that the median age of patients in the MV group (61
      years, range 50-73 years) (P = 0.0141). There was no significant difference in
      patient weight, height, or postoperative duration before muscle testing between
      the SV and MV groups. There were no significant differences in peak muscle torque
      or hamstring/quadriceps (H/Q) ratio between the groups. We thus conclude peak
      muscle torque and H/Q ratios were not statistically different with the SV or MV
      approach, therefore functional outcome is comparable.

PMID- 20148327
TI  - Epidemiology and imaging of the subchondral bone in articular cartilage repair.
AB  - Articular cartilage and the subchondral bone act as a functional unit. Following
      trauma, osteochondritis dissecans, osteonecrosis or osteoarthritis, this intimate
      connection may become disrupted. Osteochondral defects-the type of defects that
      extend into the subchondral bone-account for about 5% of all articular cartilage
      lesions. They are very often caused by trauma, in about one-third of the cases by
      osteoarthritis and rarely by osteochondritis dissecans. Osteochondral defects are
      predominantly located on the medial femoral condyle and also on the patella.
      Frequently, they are associated with lesions of the menisci or the anterior
      cruciate ligament. Because of the close relationship between the articular
      cartilage and the subchondral bone, imaging of cartilage defects or cartilage
      repair should also focus on the subchondral bone. Magnetic resonance imaging is
      currently considered to be the key modality for the evaluation of cartilage and
      underlying subchondral bone. However, the choice of imaging technique also
      depends on the nature of the disease that caused the subchondral bone lesion. For
      example, radiography is still the golden standard for imaging features of
      osteoarthritis. Bone scintigraphy is one of the most valuable techniques for
      early diagnosis of spontaneous osteonecrosis about the knee. A CT scan is a
      useful technique to rule out a possible depression of the subchondral bone plate,
      whereas a CT arthrography is highly accurate to evaluate the stability of the
      osteochondral fragment in osteochondritis dissecans. Particularly for the problem
      of subchondral bone lesions, image evaluation methods need to be refined for
      adequate and reproducible analysis. This article highlights recent studies on the
      epidemiology and imaging of the subchondral bone, with an emphasis on magnetic
      resonance imaging.

PMID- 20148328
TI  - Long-term outcome of symptomatic severe ostial vertebral artery stenosis (OVAS).
AB  - INTRODUCTION: The optimal management of patients with symptomatic severe ostial
      vertebral artery stenosis (OVAS) is currently unclear. We analyzed the long-term
      outcome of consecutive patients with OVAS who received either medical treatment
      (MT) or vertebral artery stenting (VAS). METHODS: Thirty-nine (>70%) patients
      with severe OVAS were followed for a mean period of 2.8 years. The decision for
      VAS (n = 10) or MT (n = 29) was left to the clinician. The Kaplan-Meier method
      was used to assess the risk of recurrent stroke, transient ischemic attack (TIA),
      or death over the study period. RESULTS: Patients in the VAS group were
      significantly younger and more likely to have bilateral VA disease (P = 0.04 and
      P = 0.02). VAS was successfully performed in all ten patients. The periprocedural
      risk within 30 days was 10% (one TIA). The overall restenosis rate was 10%. One
      restenosis occurred after 9 months in a patient treated with bare-metal stent. At
      4 years of follow-up, VAS showed a nonsignificant trend toward a lower risk for
      the combined endpoint of TIA and stroke in posterior circulation compared to
      medical treatment (10% vs. 45%, P = 0.095; relative risk (RR) = 0.24, 95%
      confidence interval (CI) 0.031-1.85). Patients with bilateral VA disease had a
      significantly lower recurrence risk after VAS compared with medical treatment (0%
      vs. 91% at 4 years, P = 0.004; RR 0.10, 95% CI 0.022-0.49) CONCLUSION: VAS was
      performed without permanent complications in this small series of patients with
      symptomatic severe OVAS. The long-term benefit seems to be confined to patients
      with bilateral but not to those with unilateral VA disease.

PMID- 20148329
TI  - External jig-aided intramedullary interlocking nailing of diaphyseal fractures:
      experience from a tropical developing centre.
AB  - Intramedullary interlocking nailing for diaphyseal fractures is a standard
      treatment option in affluent societies. These procedures are often performed
      under image intensifier guidance. The cost of these gadgets precludes their
      common use in resource poor regions. External jig-aided intramedullary
      interlocking nailing is relatively cheap and offers the chance for performing
      these procedures in resource poor regions. The aim of this study was to document
      the advantages, challenges and outcome of this form of treatment in a resource
      poor setting. The Surgical Implant Generation Network (SIGN) implants and
      instrumentation were used for this study. Thirty-seven limbs in 35 patients were
      included. There were 30 males and five females giving a ratio of 6:1. The mean
      age was 35 +/- 11.9 years with a range of 15-61 years. The femur and tibia were
      the bones studied with a total of 23 and 14 fractures, respectively (ratio
      1.6:1). There were 14 comminuted fractures, two segmented fractures, six mal
      unions, eight non-unions and seven simple fractures. Road traffic accidents were
      the most common cause of injuries with motorcycle accidents accounting for 19
      (57.4%) cases. The mean follow-up period was 22 +/- 5.32 months, mean time to
      union was 16.9 +/- 5.4 weeks and the major complication was osteomyelitis
      (10.8%). We conclude that this is a viable treatment option for musculoskeletal
      injuries in resource poor regions. Education to encourage early acceptance of
      surgical intervention and reduced patronage of traditional bone setting for
      injudicious interventions can reduce the infective complication rates.

PMID- 20148330
TI  - Stability of differential susceptibility and infectivity epidemic models.
AB  - We introduce classes of differential susceptibility and infectivity epidemic
      models. These models address the problem of flows between the different
      susceptible, infectious and infected compartments and differential death rates as
      well. We prove the global stability of the disease free equilibrium when the
      basic reproduction ratio R0<=1 and the existence and uniqueness of an endemic
      equilibrium when R0>1. We also prove the global asymptotic stability of the
      endemic equilibrium for a differential susceptibility and staged progression
      infectivity model, when R0>1. Our results encompass and generalize those of Hyman
      and Li (J Math Biol 50:626-644, 2005; Math Biosci Eng 3:89-100, 2006).

PMID- 20148331
TI  - The risk of non-sustained ventricular tachycardia after percutaneous alcohol
      septal ablation in patients with hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Percutaneous alcohol septal ablation (ASA) becomes an alternative
      option of treatment for symptomatic patients with hypertrophic obstructive
      cardiomyopathy (HOCM). The procedure relieves left ventricular outflow tract
      obstruction, but produces a myocardial scar in patients who already have a
      substrate for life-threatening ventricular arrhythmia. OBJECTIVES: To examine the
      effect of ASA on the occurrence of non-sustained ventricular tachycardia (nsVT)
      on 24 h ambulatory Holter monitoring in HOCM patients. METHODS: Sixty-one
      consecutive patients (34 males, mean age 48 years), who underwent ASA between
      1997 and 2003 were analyzed. Holter recordings were performed in each patient
      before and after ablation. RESULTS: Follow-up ranged from 60 to 125 months
      (median 116 months). The mean number of Holter recordings per patient was 2.7
      (range 1-11) before and 8.3 (range 2-23) after ASA (p < 0.001). Non-sustained
      ventricular tachycardia occurred in 14 patients before and 27 patients after ASA
      (23 vs. 44%, p = 0.01). The percentage of Holter recordings with nsVT before and
      after ablation was similar (14.5 vs. 15.7%, p = 0.56, respectively). No
      difference was observed between the number of nsVT per Holter recording before
      and after ablation (0.21 vs. 0.24%, p = 0.65, respectively). The percentage of
      patients with nsVT after ASA was comparable to the proportion of patients with
      nsVT in a control group consisting of 705 patients with hypertrophic
      cardiomyopathy under follow-up at our institution (44.3 vs. 43.2%, p = 0.91).
      There was no significant difference in percentage of Holter recordings with nsVT
      with respect to sex, amount of alcohol used during ASA, peak creatine
      phosphokinase level, and gradient reduction at rest. CONCLUSION: Alcohol septal
      ablation affected neither the percentage of Holter recordings with nsVT nor the
      number of nsVT episodes per Holter recording among HOCM patients.

PMID- 20148334
TI  - Central pontine and extrapontine myelinolysis: from epileptic and other
      manifestations to cognitive prognosis.
AB  - The objective of this study is to review the presentation, outcome and aetiology
      of central pontine and extrapontine myelinolysis (CPEPM) in a tertiary hospital
      center. The study method is a case series and included identification of patients
      from University of Montreal Health Centre archives database (1995-2007). All
      diagnoses were confirmed by neuroimaging or brain autopsy. Twelve individuals (25
      66 years old) presented heterogeneous manifestations. Co-morbidities included
      diabetes insipidus (n = 2), haemodialysis (n = 1), cirrhosis (n = 3),
      gastroenteritis (n = 2) and potomania (n = 1). Aetiologies included rapid
      correction of severe hyponatremia (n = 6)/acute hypernatremia (n = 1); immediate
      (n = 2) or remote (n = 1 with recurrent cirrhosis) orthotopic liver
      transplantation (OLT) with tacrolimus-induced immunosuppression (n = 3); and
      chronic alcoholism (n = 4, two with hyponatremia). Four individuals died acutely.
      Two were lost to follow-up. Six had good motor or cerebellar recovery.
      Neuropsychological evaluations (n = 5/6) revealed a subcortical/frontal
      dysfunction. Cognitive impairment represented the major remaining lasting sequel
      (n = 4). Three salient clinical syndromes were observed: (1) predominant
      cerebellar presentation in individuals with alcoholism (n = 4); (2) significant
      alteration of consciousness at presentation (n = 4), all resulting in death (OLT,
      n = 3); (3) seizures persisting after natremia correction (n = 2). Clinical
      presentation of CPEPM is heterogeneous and can even include seizures. Cognitive
      impairment should be screened as it is a significant factor limiting return to
      normal life.

PMID- 20148332
TI  - Neural correlates of aversive conditioning: development of a functional imaging
      paradigm for the investigation of anxiety disorders.
AB  - The purpose of the present study was to establish a short paradigm for the
      examination of classical aversive conditioning processes for application in
      patients with anxiety disorders. We measured behavioral, autonomic and neural
      correlates of the paradigm in healthy subjects, applying functional magnetic
      resonance imaging (fMRI) and measurement of skin conductance. Therefore, neutral
      visual stimuli were paired with an unpleasant white noise as unconditioned
      stimulus. Twenty healthy subjects performed three experimental phases of
      learning: familiarization, acquisition and extinction. Subjective ratings of
      valence and arousal after each phase of conditioning as well as skin conductance
      measurement indicated successful conditioning. During acquisition, fMRI results
      showed increased activation for the conditioned stimulus (CS+(unpaired)) when
      compared with the non-conditioned stimulus (CS-) in the right amygdala, the
      insulae, the anterior cingulate cortex and the parahippocampal gyrus, all regions
      known to be involved in emotional processing. In addition, a linearly decreasing
      activation in the right amygdala/hippocampus for the CS- across the acquisition
      phase was found. There were no significant differences between CS+ and CS- during
      extinction. In conclusion, the applicability of this paradigm for the evaluation
      of neural correlates in conditioning and extinction processes has been proven.
      Thus, we present a promising paradigm for the examination of the fear-circuit in
      patients with anxiety disorders and additionally effects of cognitive-behavioral
      interventions.

PMID- 20148335
TI  - Does clinical rapid eye movement behavior disorder predict worse outcomes in
      Parkinson's disease?
AB  - Our purpose of this study was to investigate whether clinical rapid eye movement
      sleep behavior disorder (RBD) is indicative of more widespread degenerative
      changes in Parkinson's disease (PD), using a longitudinal cohort. In 2005 and
      2007, we prospectively collected clinical and treatment characteristics of 61
      consecutive patients with PD. The presence of RBD was assessed by spouse
      interview. Sixty-four percent of patients had clinical RBD in 2005, versus 52% of
      patients in 2007. The yearly incidence rate of clinical RBD onset was 9%, while
      clinical RBD disappeared in 14% of patients per year. The motor disability scores
      (when treated) were worse in patients with than without clinical RBD in 2005, but
      not in 2007. There was no difference between groups for frequency of freezing,
      falls, and hallucinations, or for scores on the depression scale, sleepiness
      scale, mini-mental state examination and frontal assessment battery at the
      beginning versus the end of the study. Patients with clinical RBD were disabled
      earlier than patients without RBD, but there was no specific worsening in the RBD
      group with time, either for motor or non-motor symptoms. The fluctuation and
      disappearance of clinical RBD in some patients may be due to functional
      abnormalities rather than lesions.

PMID- 20148336
TI  - Requests for euthanasia: origin of suffering in ALS, heart failure, and cancer
      patients.
AB  - In The Netherlands, relatively more patients (20%) with amyotrophic lateral
      sclerosis (ALS) die due to euthanasia or physician-assisted suicide (EAS)
      compared with patients with cancer (5%) or heart failure (0.5%). We wanted to
      gain insight into the reasons for ALS patients requesting EAS and compare these
      with the reasons of cancer and heart failure patients. Knowing disease-specific
      reasons for requesting EAS may improve palliative care in these vulnerable
      patients. The data used in the present study were derived from the Support and
      Consultation in Euthanasia in The Netherlands (SCEN) evaluation study. This study
      provided consultation reports and questionnaires filled out by the attending
      physicians from 3,337 consultations conducted by SCEN physicians in situations
      where a patient requested EAS. For this study we selected data on all ALS
      patients (n = 51), all heart failure patients (n = 61), and a random sample of 73
      cancer patients. The most frequently reported reasons for unbearable suffering
      were: fear of suffocation (45%) and dependency (29%) in ALS patients, pain (46%)
      and fatigue (28%) in cancer patients, and dyspnea (52%) and dependency (37%) in
      heart failure patients. Somatic complaints were reported more frequently as a
      reason for EAS by cancer patients [odds ratio (OR) 0.20, 95% confidence interval
      (CI) 0.09-0.46] and heart failure patients [OR 0.16, 95% CI 0.05-0.46] than by
      ALS patients. ALS patients should be helped in a timely fashion to cope with
      psychosocial symptoms, e.g., by informing them about the low risk of suffocation
      in the terminal phase and the possible means of preventing this.

PMID- 20148337
TI  - Localized intrapancreatic malignant mesothelioma: a rare entity that may be
      confused with other pancreatic neoplasms.
AB  - Malignant mesothelioma usually presents with diffuse involvement of the pleura or
      peritoneum. Circumscribed or localized malignant mesothelioma has been described
      in these locations, as well as the viscera, in which case it may cause diagnostic
      confusion with other, more common entities. Herein, we describe the first well
      documented case of primary intrapancreatic malignant mesothelioma in the English
      literature. The patient was an otherwise healthy 39-year-old woman who presented
      with a symptomatic mass in the head of the pancreas that was completely resected
      via pancreaticoduodenectomy. The tumor was composed of cysts, papillae, and
      tubules lined by cells with abundant eosinophilic cytoplasm and
      immunohistochemically expressed CA-125, calretinin, and D2-40. Follow-up revealed
      no evidence of residual or recurrent disease 32 months after surgery. This report
      also describes the clinical and pathologic characteristics of an intrapancreatic
      mesothelioma and provides a review of the literature regarding entities that may
      be considered in the differential diagnosis of this tumor.

PMID- 20148338
TI  - Apparent bias for P. falciparum parasites carrying the wild-type pfcrt allele in
      the placenta.
AB  - Resistance to chloroquine has been linked to polymorphisms within the pfcrt gene
      of the human malarial parasite Plasmodium falciparum. Here, we have investigated
      the prevalence of the pfcrt allele associated with chloroquine resistance in the
      peripheral blood and the placenta of pregnant women diagnosed with a P.
      falciparum infection. Our molecular epidemiological data show an unequal
      distribution with a significant under-representation of parasites carrying the
      mutated pfcrt allele in the placenta, as compared to the peripheral blood. In
      comparison, no differences were seen with regard to pfmdr1 polymorphisms of these
      parasites. Our data suggest a selective disadvantage of the polymorphic and a
      selective advantage of the wild-type pfcrt haplotype in the placenta, supporting
      the model that the human host provides various microenvironments that favor
      genetically distinct P. falciparum populations.

PMID- 20148339
TI  - Extraintestinal helminths of the common vole (Microtus arvalis) and the water
      vole (Arvicola terrestris) in Western Austria (Vorarlberg).
AB  - Between September and December 2004, a total of 411 voles (318 common voles and
      93 water voles) were caught in the Austrian province of Vorarlberg (Lustenau,
      Hohenems, and Dornbirn) and were examined by macroscopy, microscopy, and
      molecular biological analysis to determine the presence and extent of medically
      important extraintestinal helminths. The following extraintestinal helminth
      species were detected: Taenia taeniaeformis (liver), Calodium hepaticum (liver),
      and Echinococcus multilocularis DNA (liver) in the common vole; and Taenia
      taeniaeformis (liver), Calodium hepaticum (liver), and Taenia crassiceps
      (musculature) in the water vole. Infestations with Toxocara canis and Trichinella
      sp. were not found. Our study documents the first description of E.
      multilocularis DNA in the intermediate host (Microtus arvalis) and of other
      medically relevant extraintestinal helminths in common and water voles in
      Austria.

PMID- 20148340
TI  - Clinical characteristics and outcomes of children with stage 3-5 chronic kidney
      disease.
AB  - The aim of this study was to report on the clinical characteristics and outcomes
      of Belgian children with chronic kidney disease (CKD). Between 2001 and 2005, we
      followed 143 new successive patients younger than 20 years of age with a
      glomerular filtration rate of <60 ml/min/1.73 m(2) prospectively in a Belgian
      department of pediatric nephrology. The incidence of diagnosed CKD was 11.9 per
      million child population (pmcp), and the incidence of renal replacement therapy
      was 6.2 pmcp. There were 67% patients in CKD stage 3, 19% in CKD stage 4 and 14%
      in CKD stage 5. Patients with congenital anomalies of the kidney and urinary
      tract (CAKUTs), hereditary diseases and glomerular diseases were diagnosed at a
      median age of 1, 2 and 10 years, respectively. CAKUTs were the main causes of
      CKD, accounting for 59% of all cases. After 3, 4 and 5 years of follow-up, 27, 31
      and 38% of patients treated conservatively, respectively, reached end-stage renal
      failure (ESRF). The progression rate to ESRF was eightfold higher in patients
      with CKD stage 4 than in those with CKD stage 3. Among our patient group,
      hereditary diseases progressed more rapidly to ESRF than CAKUTs. Transplantation
      was performed preemptively in 22% of these children. Infections and
      cardiovascular diseases were the main causes of death.

PMID- 20148341
TI  - Gait in thoracolumbar/lumbar adolescent idiopathic scoliosis: effect of surgery
      on gait mechanisms.
AB  - For patients whose scoliosis progresses, surgery remains the ultimate way to
      correct and stabilise the deformity while maintaining as many mobile spinal
      segments as possible. In thoracolumbar/lumbar adolescent idiopathic scoliosis
      (AIS), the spinal fusion has to be extended to the lumbar spine. The use of
      anterior spinal fusion (ASF) instead of the classic posterior fusion (PSF) may
      preserve more distal spinal levels in attempt to limit the consequences of
      surgery on trunk mobility. The effects of surgery on body shape, pain and the
      decompensation phenomenon have all been well evaluated. Very few studies have
      addressed the effect of ASF or PSF on basic activities, such as walking. Before
      any treatment, AIS patients already have reduced pelvis, hip and shoulder motion
      when walking at a normal speed compared with adolescents without scoliosis
      (control group). Additionally, they have longer contraction time of the lumbar
      and pelvic muscles leading to an excessive energy cost and reduced muscle
      efficiency. In addition, if these changes are associated with spinal stiffness,
      spinal fusion could further negatively affect this pre-surgical inefficient walk.
      The goals of this study were (a) to compare pre- and 1-year post-surgery
      conditions in order to assess the effects of spinal arthrodesis on gait
      parameters and (b) to compare the anterior versus the posterior surgical
      approaches. Nineteen young females with thoracolumbar/lumbar AIS were assessed by
      radiological and clinical examination and by conventional gait analysis before
      surgery and at almost 12 months after surgery. Seven subjects underwent surgery
      using ASF and 12 using PSF. Three-dimensional gait analysis was performed on a
      motor-driven treadmill at spontaneous self-selected speed to record kinematic,
      electromyographic (EMG), mechanical and energetic measurements synchronously.
      Although it was expected that the instrumentation would modify the
      characteristics of normal walking, this study showed that surgery does not induce
      asymmetric gait or any significant differences between the ASP and the PSF
      surgery groups. One year after surgery, the changes observed consisted of
      improvements in the gait and mechanical parameters. In the PSF group, 11-14
      vertebrae were fused while only 3-4 were fused in the ASF group. In both AIS
      groups, step length was increased by 4% and cadence reduced by 2%. There was a
      slight increase in pelvis and hip frontal motion. Only the transverse shoulder
      motion was mildly decreased by 1.5 degrees . All the other gait parameters were
      left unchanged or were improved by surgery. Notably, the EMG timing activity did
      not change. The total muscular mechanical work (W (tot)) increased by 6% mainly
      due to the external work (W (ext)), i.e. the work performed by the body muscles
      to move the body in its surroundings. The energy cost, although showing a
      tendency towards a reduction, remained globally excessive, probably due to the
      excessive co-contraction of the lumbo-pelvic muscles.

PMID- 20148342
TI  - Transglutaminase 2: a multi-functional protein in multiple subcellular
      compartments.
AB  - Transglutaminase 2 (TG2) is a multifunctional protein that can function as a
      transglutaminase, G protein, kinase, protein disulfide isomerase, and as an
      adaptor protein. These multiple biochemical activities of TG2 account for, at
      least in part, its involvement in a wide variety of cellular processes
      encompassing differentiation, cell death, inflammation, cell migration, and wound
      healing. The individual biochemical activities of TG2 are regulated by several
      cellular factors, including calcium, nucleotides, and redox potential, which vary
      depending on its subcellular location. Thus, the microenvironments of the
      subcellular compartments to which TG2 localizes, such as the cytosol, plasma
      membrane, nucleus, mitochondria, or extracellular space, are important
      determinants to switch on or off various TG2 biochemical activities. Furthermore,
      TG2 interacts with a distinct subset of proteins and/or substrates depending on
      its subcellular location. In this review, the biological functions and molecular
      interactions of TG2 will be discussed in the context of the unique environments
      of the subcellular compartments to which TG2 localizes.

PMID- 20148343
TI  - A positional coding mechanism in pigeons after learning multiple three-item
      lists.
AB  - Pigeons were trained on three three-item lists (List 1: A(1) --> B(1) --> C(1;)
      List 2: A(2) --> B(2) --> C(2;) List 3: A(3) --> B(3) --> C(3)). After sessions
      in which any one of the three lists could be presented on a trial, derived
      maintained list and derived-changed list probe trials were introduced. The
      derived list probe trials were composed of three items, one drawn from each of
      the training lists. On derived-maintained probe trials, each item was in the same
      ordinal position it occupied during training (e.g., A(3) --> B(1) --> C(2)). On
      derived-changed probe trials, items that occupied the second and third position
      during training were exchanged (e.g., A(2) --> C(3) --> B(1)). The performance of
      subjects on derived-maintained probe trials was significantly above chance and no
      different to that observed on the training lists. In contrast, subjects'
      performance on derived-changed probe trials was significantly below chance. To
      our knowledge, this is the first study that has demonstrated pigeons are able to
      learn and retain multiple three-item lists. In addition, subjects' performance on
      the derived-maintained probe trials suggests that they acquire knowledge of each
      list item's ordinal position when learning multiple lists.

PMID- 20148344
TI  - A modified mark test for own-body recognition in pig-tailed macaques (Macaca
      nemestrina).
AB  - Classic mirror self-recognition mark tests involve familiarizing the subject with
      its mirror image, surreptitiously applying a mark on the subject's eyebrow, nose,
      or ear, and measuring self-directed behaviors toward the mark. For many non-human
      primate species, however, direct gaze at the face constitutes an aggressive and
      threatening signal. It is therefore possible that monkeys fail the mark test
      because they do not closely inspect their faces in a mirror and hence they have
      no expectations about their physical appearance. In the current study, we
      prevented two pig-tailed macaques (Macaca nemestrina) from seeing their own faces
      in a mirror, and we adopted a modified version of the classic mark test in which
      monkeys were marked on the chest, a body region to which they normally have
      direct visual access but that in the current study was visible only via a mirror.
      Neither monkey tried to touch the mark on its chest, possibly due to a failure to
      understand the mirror as a reflective surface. To further the monkeys'
      understanding of the mirror image, we trained them to reach for food using the
      mirror as the only source of information. After both monkeys had learned mirror
      mediated reaching, we replicated the mark test. In this latter phase of the
      study, only one monkey scratched the red dye on the chest once. The results are
      consistent with other findings suggesting that monkeys are not capable of passing
      a mark test and imply that face and body recognition rely on the same cognitive
      abilities.

PMID- 20148345
TI  - Characterizing the mechanical contribution of fiber angular distribution in
      connective tissue: comparison of two modeling approaches.
AB  - Modeling of connective tissues often includes collagen fibers explicitly as one
      of the components. These fibers can be oriented in many directions; therefore,
      several studies have considered statistical distributions to describe the fiber
      arrangement. One approach to formulate a constitutive framework for distributed
      fibers is to express the mechanical parameters, such as strain energy and
      stresses, in terms of angular integrals. These integrals represent the addition
      of the contribution of infinitesimal fractions of fibers oriented in a given
      direction. This approach leads to accurate results; however, it requires lengthy
      calculations. Recently, the use of generalized structure tensors has been
      proposed to represent the angular distribution in the constitutive equations of
      the fibers. Although this formulation is much simpler and fewer calculations are
      required, such structure tensors can only be used when all the fibers are in
      tension and the angular distribution is small. However, the amount of error
      introduced in these cases of non-tensile fiber loading and large angular
      distributions have not been quantified. Therefore, the objective of this study is
      to determine the range of values of angular distribution for which acceptable
      differences (less than 10%) between these two formulations are obtained. It was
      found, analytically and numerically, that both formulations are equivalent for
      planar distributions under equal-biaxial stretch. The comparison also showed, for
      other loading conditions, that the differences decrease when the fiber
      distribution is very small. Differences of less than 10% were usually obtained
      when the fiber distribution was very low (kappa ~ 0.03; kappa ranges between 0
      and 1/3, for aligned and isotropic distributed fibers, respectively). This range
      of angular distribution greatly limits the types of tissue that can be accurately
      analyzed using generalized structure tensors. It is expected that the results
      from this study guide the selection of a proper approach to analyze a particular
      tissue under a particular loading condition.

PMID- 20148346
TI  - The influence of exogenous cross-linking and compressive creep loading on
      intradiscal pressure.
AB  - This study involves a biomechanical evaluation of a prospective injectable
      treatment for degenerative discs. The high osmolarity of the non-degenerated
      nucleus pulposus attracts water contributing to the hydrostatic behavior of the
      tissue. This intradiscal pressure is known to drop as fluid is exuded from the
      matrix due to compressive loading. The objective of this study was to compare the
      changes in intradiscal pressure in control and genipin cross-linked
      intervertebral discs. Thirty bovine lumbar motion segments were randomly divided
      into a phosphate-buffered saline control group and a 0.33% genipin group and
      soaked at room temperature for 2 days. A needle pressure sensor was held in the
      center of the disc while short-term and static creep compressive loads were
      applied. The control group demonstrated a 25% higher average intradiscal pressure
      compared to genipin-treated discs under 750 N compressive load (p=0.029).
      Depressurization during static compressive creep was 56% higher in the control
      than in the genipin group (p=0.014). These results suggest cross-linking induced
      changes in the poroelastic properties of the involved tissues affected the
      mechanics of compressive load support in the disc with lower levels of nucleus
      pressure, a corresponding decrease in the elastic expansion of the annulus, and
      an increased axial compressive loading of the inner and outer annulus tissues. It
      is possible that concurrent changes in hydraulic permeability and proteoglycan
      retention known to be associated with genipin cross-linking were also
      contributors to poroelastic changes. Reduction of peak pressures and moderation
      of pressure fluctuations could be beneficial relative to discogenic pain.

PMID- 20148347
TI  - Design optimization of a helical endothelial cell culture device.
AB  - The specific roles of mass transfer and fluid dynamic stresses on endothelial
      function, important in atherogenesis, are not known. Further, the effects of mass
      transfer and fluid dynamic stresses are difficult to separate because areas of
      "abnormal" mass transfer and "abnormal" wall shear stress tend to co-localize
      (where abnormal is defined as any deviation from the mass transfer rate or wall
      shear stress present in a long straight artery with the same flow rate and
      diameter). Our goal was to design a cell culture device which gives maximum
      separation between areas of abnormal shear stress and areas of abnormal mass
      transfer. We used design optimization principles to design a helical cell culture
      device. Using shear stress and mass transfer fields predicted by solving the
      governing equations, the area of the device which was exposed to low rates of
      mass transfer and normal levels of wall shear stress was determined. The design
      optimization method then maximized this area by varying the design variables,
      resulting in the optimum design. The optimum design had Reynolds number = 50,
      helical radius = 3.23 and helical pitch = 3.82. The area of the device which was
      exposed to low rates of mass transfer and regular levels of wall shear stress was
      about 4.5 times the inlet cross-sectional area of the device or about 5% of the
      device total internal surface area. An optimum design was successfully determined
      and the methodology used was shown to be robust. The area of the device which was
      exposed to low rates of mass transfer and regular levels of wall shear stress
      occurred in a defined region which should aid further experimental work.

PMID- 20148348
TI  - Escalating weekly doses of cetuximab and correlation with skin toxicity: a phase
      I study.
AB  - BACKGROUND: Cetuximab is a chimeric monoclonal antibody targeting the epidermal
      growth factor receptor (EGFR). The recommended dosage is an initial load of 400
      mg/m2 intravenously (IV) followed by a weekly maintenance dose of 250 mg/m2. It
      has been reported retrospectively that cetuximab efficacy was correlated with
      dose-related severity of skin rash. This study was prospectively designed to
      examine the safety and feasibility of escalating weekly doses of cetuximab,
      testing the hypothesis of the relationship of dose-dependent skin toxicity and
      efficacy. Methods Four dose levels were tested: Cetuximab 400 mg/m2 IV loading
      dose and 250, 300, 350, 400 mg/m2 weekly IV maintenance. There was no intra
      patient dose escalation. Standard dose limiting toxicity criteria were used. Rash
      was evaluated using two additional validated dermatology methods: global acne
      grading scale (GAGS) and acne lesion counting (ALC). Tumor specimens and blood
      samples were obtained for correlative analyses. RESULTS: Twenty seven patients
      with solid tumors were enrolled: five head and neck, three pancreas, four gall
      bladder, two each of prostate, breast, colorectal, lung, and esophagus, and five
      others. Planned dose escalation was completed without reaching dose-limiting
      toxicity (DLT) or the maximum tolerated dose (MTD). The highest dose level was
      expanded to a total of 17 patients. Gr 3/4 toxicities included: lymphopenia (2),
      fatigue (2), and hypomagnesemia (2). One patient experienced a grade 3 rash (350
      mg/m2). Sixty five percent of pts had a >= Gr 2 rash that was not dose dependent.
      In 22 evaluable patients, there was one partial response (PR) in a patient with
      cholangiocarcinoma (400 mg/m2) and seven patients had stable disease (SD). ALC
      and GAGS demonstrated no correlation with dose or response. Correlative studies
      evaluating k-ras, EGFR FISH status and immunologic correlatives were conducted on
      available tumor samples. CONCLUSIONS: Cetuximab administered at 400 mg/m2 IV as a
      loading dose with weekly maintenance dose of 400 mg/m2 is feasible and well
      tolerated. There was no direct correlation of the grade of rash with dose in this
      group of patients with heterogenous solid tumors.

PMID- 20148349
TI  - The anti-proliferative side effects of AEE788, a tyrosine kinase inhibitor
      blocking both EGF- and VEGF-receptor, are liver-size-dependent after partial
      hepatectomy in rats.
AB  - BACKGROUND: Blocking of EGFR signaling by the tyrosine kinase inhibitor AEE788
      was well tolerated and did not inhibit liver regeneration after standard 70%
      partial hepatectomy (PH) in a rat model, as demonstrated previously. However,
      serum levels of AEE788 at POW1 were 3-fold higher than in the non-resected
      control group. Therefore, we expanded theses studies to a model of extended 90%PH
      to investigate the role of liver size for the metabolism of AEE788 and its
      potential influence on side effects, liver regeneration and liver remodeling.
      METHOD: Rats treated with 50 mg/kg AEE788 or solvent every other day orally were
      subjected to 90%PH. Animals were sacrificed at 1, 2, 7 and 28 days after PH. We
      measured plasma and liver levels of AEE788 and assessed anti-proliferative side
      effects, liver regeneration, and liver architecture. RESULT: Liver regeneration
      and liver architecture were not impaired by AEE788 treatment after 90%PH. 90%PH
      caused a clinically relevant drug accumulation within 1 week of treatment (AEE788
      serum and tissue levels: 90%PH*>70%PH*>normal control, *p < 0.05), suggesting a
      liver-size-dependent metabolism of the drug. Drug accumulation after 90%PH was
      associated with severe side effects (delayed body weight recovery, diarrhea,
      impaired hair growth) within 1 week of treatment. CONCLUSION: Treatment with
      AEE788 could be a potential strategy for adjuvant treatment after oncological
      liver resection, as liver regeneration was not impaired. Our results suggest a
      liver-size-dependent metabolism of AEE788 leading to drug accumulation and
      subsequently to severe side effects. It calls for therapeutic drug monitoring in
      the early postoperative phase after extended resection.

PMID- 20148351
TI  - SacRALF1, a peptide signal from the grass sugarcane (Saccharum spp.), is
      potentially involved in the regulation of tissue expansion.
AB  - Rapid alkalinization factor (RALF) is part of a growing family of small peptides
      with hormone characteristics in plants. Initially isolated from leaves of tobacco
      plants, RALF peptides can be found throughout the plant kingdom and they are
      expressed ubiquitously in plants. We took advantage of the small gene family size
      of RALF genes in sugarcane and the ordered cellular growth of the grass sugarcane
      leaves to gain information about the function of RALF peptides in plants. Here we
      report the isolation of two RALF peptides from leaves of sugarcane plants using
      the alkalinization assay. SacRALF1 was the most abundant and, when added to
      culture media, inhibited growth of microcalli derived from cell suspension
      cultures at concentrations as low as 0.1 microM. Microcalli exposed to exogenous
      SacRALF1 for 5 days showed a reduced number of elongated cells. Only four copies
      of SacRALF genes were found in sugarcane plants. All four SacRALF genes are
      highly expressed in young and expanding leaves and show a low or undetectable
      level of expression in expanded leaves. In half-emerged leaf blades, SacRALF
      transcripts were found at high levels at the basal portion of the leaf and at low
      levels at the apical portion. Gene expression analyzes localize SacRALF genes in
      elongation zones of roots and leaves. Mature leaves, which are devoid of
      expanding cells, do not show considerable expression of SacRALF genes. Our
      findings are consistent with SacRALF genes playing a role in plant development
      potentially regulating tissue expansion.

PMID- 20148350
TI  - Constitutive expression of mustard annexin, AnnBj1 enhances abiotic stress
      tolerance and fiber quality in cotton under stress.
AB  - Annexins belong to a multigene family of Ca(2+) dependent, phospholipid and
      cytoskeleton binding proteins. They have been shown to be upregulated under
      various stress conditions. We generated transgenic cotton plants expressing
      mustard annexin (AnnBj1), which showed enhanced tolerance towards different
      abiotic stress treatments like sodium chloride, mannitol, polyethylene glycol and
      hydrogen peroxide. The tolerance to these treatments was associated with
      decreased hydrogen peroxide levels and enhanced total peroxidase activity,
      enhanced content of osmoprotectants- proline and sucrose in transgenic plants.
      They showed higher retention of total chlorophyll and reduced TBARS in leaf disc
      assays with stress treatments, and decreased hydrogen peroxide accumulation in
      the stomatal guard cells when compared to their wild type counterparts. They also
      showed significantly enhanced fresh weight, relative water content, dry weight
      under stress. Treatment with sodium chloride resulted in enhanced expression of
      genes for Delta-pyrroline-5-carboxylase synthetase in leaves, and sucrose
      phosphate synthase, sucrose synthase and cellulose synthase A in the leaves and
      fibers of transgenic plants. The transgenic plants maintained normal seed
      development, fiber quality and cellulose content under stress.

PMID- 20148352
TI  - Fasting promotes the expression of SIRT1, an NAD+ -dependent protein deacetylase,
      via activation of PPARalpha in mice.
AB  - Calorie restriction (CR) extends lifespans in a wide variety of species. CR
      induces an increase in the NAD(+)/NADH ratio in cells and results in activation
      of SIRT1, an NAD(+)-dependent protein deacetylase that is thought to be a
      metabolic master switch linked to the modulation of lifespans. CR also affects
      the expression of peroxisome proliferator-activated receptors (PPARs). The three
      subtypes, PPARalpha, PPARgamma, and PPARbeta/delta, are expressed in multiple
      organs. They regulate different physiological functions such as energy
      metabolism, insulin action and inflammation, and apparently act as important
      regulators of longevity and aging. SIRT1 has been reported to repress the
      PPARgamma by docking with its co-factors and to promote fat mobilization.
      However, the correlation between SIRT1 and other PPARs is not fully understood.
      CR initially induces a fasting-like response. In this study, we investigated how
      SIRT1 and PPARalpha correlate in the fasting-induced anti-aging pathways. A 24-h
      fasting in mice increased mRNA and protein expression of both SIRT1 and PPARalpha
      in the livers, where the NAD(+) levels increased with increasing nicotinamide
      phosphoribosyltransferase (NAMPT) activity in the NAD(+) salvage pathway.
      Treatment of Hepa1-6 cells in a low glucose medium conditions with NAD(+) or NADH
      showed that the mRNA expression of both SIRT1 and PPARalpha can be enhanced by
      addition of NAD(+), and decreased by increasing NADH levels. The cell experiments
      using SIRT1 antagonists and a PPARalpha agonist suggested that PPARalpha is a key
      molecule located upstream from SIRT1, and has a role in regulating SIRT1 gene
      expression in fasting-induced anti-aging pathways.

PMID- 20148353
TI  - Irradiation with heavy-ion particles changes the cellular distribution of human
      histone acetyltransferase HAT1.
AB  - Hat1 was the first histone acetyltransferase identified; however, its biological
      function is still unclear. In this report, it is shown for the first time that
      human Hat1 has two isoforms. Isoform a has 418 amino acids (aa) and is localized
      exclusively in the nuclear matrix of normal human keratinocytes (NHKs). Isoform b
      has 334 aa and is located in the cytoplasm, the nucleoplasm, attached to the
      chromatin and to the nuclear matrix. Immunohistochemical analyses revealed that
      the bulk of Hat1 is confined to the nucleus, with much lesser amounts in the
      cytoplasm. Cells undergoing mitotic division have an elevated amount of Hat1
      compared to those that are non-mitotic. Senescent cells, however, exhibit a
      higher concentration of Hat1 in the cytoplasm compare to proliferating cells and
      the amount of Hat1 in the nucleus decreases with the progression of senescence.
      NHKs exposed to hydrogen peroxide (H(2)O(2)) or to a beam of high mass and energy
      ion particles displayed bright nuclear staining for Hat1, a phenotype that was
      not observed in NHKs exposed to gamma-rays. We established that the enhanced
      nuclear staining for Hat1 in response to these treatments is regulated by the
      PI3K and the mitogen-activated protein kinase signaling pathways. Our
      observations clearly implicate Hat1 in the cellular response assuring the
      survival of the treated cells.

PMID- 20148354
TI  - Suppression of the androgen receptor function by quercetin through protein
      protein interactions of Sp1, c-Jun, and the androgen receptor in human prostate
      cancer cells.
AB  - We have previously reported that the increase in c-Jun expression induced by
      quercetin inhibited androgen receptor (AR) transactivation, and Sp1 was involved
      in quercetin-mediated downregulation of AR activity. Transient transfection
      assays in this work revealed that co-expression of c-Jun quenched Sp1-induced
      production of luciferase activity driven by AR promoter or three copies of Sp1
      binding elements in the AR promoter. Moreover, c-Jun repressed AR-mediated
      luciferase activity via androgen-response elements (AREs) of the hK2 gene, while
      this suppression could be restored partially by cotransfection of Sp1 expression
      plasmid. The physical associations of c-Jun, Sp1, and AR induced by quercetin
      were further demonstrated by co-immunoprecipitation experiments. In addition,
      quercetin-mediated repression of AR expression and activity was partially
      reversed by blocking of JNK signaling pathway. These results suggested that c-Jun
      might play an important role in the suppression of AR expression and activity in
      the presence of quercetin, and association of a c-Jun/Sp1/AR protein complex
      induced by quercetin represented a novel mechanism that was involved in down
      regulation of the AR function in prostate cancer cells.

PMID- 20148355
TI  - Angiostatic effects of K252a, a Trk inhibitor, in murine brain capillary
      endothelial cells.
AB  - Nerve growth factor (NGF) supports the survival and differentiation of
      sympathetic and sensory neurons and is also mitogenic for a variety of tumors.
      K252a, an antagonist of NGF receptor TrkA, was previously used as a
      pharmacological tool to study NGF actions and as a lead compound for developing
      anti-tumor drugs. Since recently, NGF was characterized as an angiogenic factor,
      we sought to investigate the angiostatic properties of K252a on endothelial cells
      (ECs). For this purpose, we used a murine brain microcapillary ECs model in which
      we found autocrine release of NGF in the culture medium and activation of TrkA
      receptor-induced downstream signaling molecules Erk1/2, Akt, and PLCgamma. In
      this model, we demonstrated the angiostatic property of K252a based on its
      ability to affect several important angiogenic steps. K252a, but not its cell
      membrane impermeable analogue K252b at 100 nM: (i) inhibited the proliferation of
      the ECs by 45 +/- 9%; (ii) reduced by 70 +/- 4% the migration of the ECs measured
      in a wound-closure model; (iii) reduced by 29 +/- 9% the formation of tube-like
      structures of the ECs cultured on Matrigel; (iv) stimulated by 100 +/- 25% the
      collagen deposition by the ECs, a process responsible for the increased
      endothelial barrier functions expressed by 22 +/- 5% reduction of paracellular
      permeability and by 17 +/- 3% elevation of transendothelial electrical
      resistance. These data suggest that NGF/TrkA may represent a target for the
      development of novel, K252a-derived multikinase inhibitors drugs with anti-tumor
      and angiostatic dual activities.

PMID- 20148357
TI  - Foliar mono- and sesquiterpene contents in relation to leaf economic spectrum in
      native and alien species in Oahu (Hawai'i).
AB  - Capacity for terpene production may confer advantage in protection against
      abiotic stresses such as heat and drought, and also against herbivore and
      pathogen attack. Plant invasive success has been intense in the Hawaiian islands,
      but little is known about terpene content in native and alien plant species on
      these islands. We conducted a screening of leaf terpene concentrations in 35
      native and 38 alien dominant plant species on Oahu island. Ten (29%) of the 35
      native species and 15 (39%) of the 38 alien species contained terpenes in the
      leaves. This is the first report of terpene content for the ten native species,
      and for 10 of the 15 alien species. A total of 156 different terpenes (54
      monoterpenes and 102 sesquiterpenes) were detected. Terpene content had no
      phylogenetic significance among the studied species. Alien species contained
      significantly more terpenes in leaves (average+/-SE=1965+/-367 microg g(-1)) than
      native species (830+/-227 microg g(-1)). Alien species showed significantly
      higher photosynthetic capacity, N content, and lower Leaf Mass Area (LMA) than
      native species, and showed higher total terpene leaf content per N and P leaf
      content. Alien species, thus, did not follow the expected pattern of "excess
      carbon" in comparison with native species. Instead, patterns were consistent with
      the "nutrient driven synthesis" hypothesis. Comparing alien and native species,
      the results also support the modified Evolution of Increased Competitive Ability
      (EICA) hypothesis that suggests that alien success may be favored by a defense
      system based on an increase in concentrations of less costly defenses (terpenes)
      against generalist herbivores.

PMID- 20148356
TI  - Plants on constant alert: elevated levels of jasmonic acid and jasmonate-induced
      transcripts in caterpillar-resistant maize.
AB  - This study was conducted to determine if constitutive levels of jasmonic acid
      (JA) and other octadecanoid compounds were elevated prior to herbivory in a maize
      genotype with documented resistance to fall armyworm (Spodoptera frugiperda) and
      other lepidopteran pests. The resistant inbred Mp708 had approximately 3-fold
      higher levels of jasmonic acid (JA) prior to herbivore feeding than the
      susceptible inbred Tx601. Constitutive levels of cis-12-oxo-phytodienoic acid
      (OPDA) also were higher in Mp708 than Tx601. In addition, the constitutive
      expression of JA-inducible genes, including those in the JA biosynthetic pathway,
      was higher in Mp708 than Tx601. In response to herbivory, Mp708 generated
      comparatively higher levels of hydrogen peroxide, and had a greater abundance of
      NADPH oxidase transcripts before and after caterpillar feeding. Before herbivore
      feeding, low levels of transcripts encoding the maize insect resistance cysteine
      protease (Mir1-CP) and the Mir1-CP protein were detected consistently. Thus,
      Mp708 appears to have a portion of its defense pathway primed, which results in
      constitutive defenses and the ability to mount a stronger defense when
      caterpillars attack. Although the molecular mechanisms that regulate the
      constitutive accumulation of JA in Mp708 are unknown, it might account for its
      enhanced resistance to lepidopteran pests. This genotype could be valuable in
      studying the signaling pathways that maize uses to response to insect herbivores.

PMID- 20148358
TI  - Semiochemical-mediated oviposition avoidance by female house flies, Musca
      domestica, on animal feces colonized with harmful fungi.
AB  - House flies, Musca domestica, utilize ephemeral resources such as animal feces
      for oviposition and development of larval offspring, but they face competition
      with fungi that colonize the same resource. We predicted that house flies avoid
      oviposition on feces well-colonized with fungi, thereby reducing fungal
      competition for larval offspring. Working with fungal isolates from chicken
      feces, we have previously shown that prior establishment of Phoma spp., Fusarium
      spp., or Rhizopus spp. on feces significantly reduced oviposition by house flies.
      Here, we report that, in the headspace volatiles of these three fungal genera,
      five compounds (dimethyl trisulfide, an unknown, 2-phenylethanol, citronellal,
      norphytone) elicit responses from house fly antennae. In behavioral bioassays,
      dimethyl trisulfide and 2-phenylethanol significantly reduced oviposition by
      house flies. We conclude that fungus-derived volatiles serve as semiochemical
      cues that help house flies avoid resources colonized with fungal competitors for
      the development of larval offspring.

PMID- 20148359
TI  - Mexican-origin adolescent mothers' stressors and psychosocial functioning:
      examining ethnic identity affirmation and familism as moderators.
AB  - Mexican-origin adolescent mothers are at increased risk for poor psychosocial
      functioning as a result of various stressors with which they must contend;
      however, existing theory suggests that cultural strengths may help mitigate the
      negative effects of stress. As such, the current study examined the associations
      between cultural and economic stressors and Mexican-origin adolescent mothers' (N
      = 207; M age = 16.23 years, SD = 1.0) internalizing and externalizing behaviors,
      as well as the degree to which ethnic identity affirmation and familism values
      moderated these links. Adolescent mothers who reported higher levels of
      discrimination, acculturative stress, and economic stress also reported higher
      depressive symptoms and greater involvement in risky behaviors. Importantly,
      ethnic identity affirmation minimized the negative associations between cultural
      stressors and adolescents' involvement in risky behaviors, with the associations
      being weakest among adolescents with high levels of ethnic identity. Familism
      appeared to serve a protective function under conditions of low levels of
      discrimination, but not under conditions of high levels of discrimination.
      Findings are discussed with special attention to the developmental and cultural
      contexts in which these adolescent mothers' lives are embedded, and implications
      for future research and practice are presented.

PMID- 20148361
TI  - Diabetes and risk of incident cancer: a large population-based cohort study in
      Israel.
AB  - Type 2 diabetes mellitus has been associated with an increased risk of a variety
      of cancers in observational studies, but few have reported the relationship
      between diabetes and cancer risk in men and women separately. The main goal of
      this retrospective cohort study was to evaluate the sex-specific risk of incident
      overall and site-specific cancer among people with DM compared with those
      without, who had no reported history of cancer at the start of the follow-up in
      January 2000. During an average of 8 years of follow-up (SD = 2.5), we documented
      1,639 and 7,945 incident cases of cancer among 16,721 people with DM and 83,874
      free of DM, respectively. In women, DM was associated with an adjusted hazard
      ratio of 1.96 (95% CI: 1.53-2.50) and 1.41 (95% CI: 1.20-1.66) for cancers of
      genital organs and digestive organs, respectively. A significantly reduced HR was
      observed for skin cancer (0.38; 95% CI: 0.22-0.66). In men with DM, there was no
      significant increase in overall risk of cancer. DM was related with a 47%
      reduction in the risk of prostate cancer. These findings suggest that the nature
      of the association between DM and cancer depends on sex and specific cancer site.

PMID- 20148360
TI  - Genetic variation in sex-steroid receptors and synthesizing enzymes and
      colorectal cancer risk in women.
AB  - OBJECTIVES: Several lines of evidence have suggested that female hormones may
      lower the risk for developing colorectal cancer. However, the mechanisms by which
      sex hormones affect colorectal cancer development remain unknown. We sought to
      determine whether the association may be under genetic control by evaluating
      genetic variation in estrogen receptors (ESR1 and ESR2), progesterone receptor
      (PGR), aromatase cytochrome 450 enzyme (CYP19A1), and 17 beta-hydroxysteroid
      dehydrogenase type 2 gene (HSD17B2). METHODS: We included 158 incident cases of
      colorectal cancer and 563 randomly chosen control subjects from 28,345 women in
      the Women's Health Study aged 45 or older who provided blood samples and had no
      history of cancer or cardiovascular disease at baseline in 1993. All cases and
      controls were Caucasians of European descent. A total of 63 tagging and putative
      functional SNPs in the 5 genes were included for analysis. Unconditional logistic
      regression was used to estimate odds ratio (ORs) and 95% confidence intervals
      (CIs). RESULTS: There was no association between variation in ESR1, ESR2, PGR,
      CYP19A1 and HSD17B2 and colorectal cancer risk after correction for multiple
      comparisons (p values after correction > or =0.25). There was also no association
      with any of the haplotypes examined (p > or = 0.15) and no evidence of joint
      effects of variants in the 5 genes (p > or = 0.51). CONCLUSION: Our data offer
      insufficient support for an association between variation in ESR1, ESR2, PGR,
      CYP19A1, and HSD17B2 and risk for developing colorectal cancer.

PMID- 20148362
TI  - Heavy metals in soils from Tirana (Albania).
AB  - This study was aimed to establish background and reference values of total heavy
      metals in soils from a representative area of Albania (Tirana). Thirty-eight soil
      samples collected from genetic horizons of major soil types of Tirana were
      analyzed for important physicochemical properties by standard methods and for
      total contents of Cd, Cr, Ni, Pb, Zn, and Cu by atomic absorption spectrometer,
      after extraction with aqua regia. The results showed that the total contents of
      Cd, Cr, Ni, Pb, Zn, and Cu in surface horizons varied widely with respective mean
      values of 0.3 (+/- 0.6), 174.2 (+/- 63.7), 305.9 (+/- 133.0), 19.7 (+/- 12.4),
      95.5 (+/- 26.3), and 42.7 (+/- 6.8) mg/kg. The highest metal contents were found
      in two soils developed in limestone. The depth distribution of metals showed a
      tendency for accumulation of Cd and Pb in the surface horizons of three soils,
      suggesting that these metals partially come from anthropogenic inputs.
      Correlation analysis indicated that the metal contents of soils were controlled
      by soil properties, including pH, CaCO3, clay, organic matter, cation exchange
      capacity, and Fe oxides. The background values (given as the 90th percentile)
      were much higher than those reported in the literature, showing that the levels
      of respective metals were naturally higher. The total metal contents of some
      soils were above background levels, suggesting metal pollution. The reference
      values for all the analyzed metals were quite consistent with those of the Dutch
      system. The proposed background and reference values can be used to evaluate the
      soil pollution with these elements.

PMID- 20148363
TI  - Quality assessment of various bottled waters marketed in Lebanon.
AB  - Thirty-two domestic bottled water brands were analyzed for various physico
      chemical as well as bacterial water quality parameters. Recorded results were
      compared with the Lebanese Standards Institution standards of quality and
      standards of identity as well as various international water standards for
      bottled waters. Results showed a widespread in the characteristics of
      investigated bottled waters, yet the majority met the different bottled water
      standards for physico-chemical parameters except for pH (4 brands), hardness (2
      brands), and calcium (2 brands). All samples showed negative growth for fecal
      coliforms, yet 18.8% (N = 6) and 59.4% (N = 19) of the samples revealed positive
      results for total coliforms and heterotrophic plate count at 37 degrees C,
      respectively. Generated Piper diagrams revealed that the majority of investigated
      waters are of calcium-magnesium bicarbonate type; some brands were rich in sodium
      potassium chloride, and few were of the mixed type. Comparison of the study
      results with reported label values indicated good agreement with stated pH values
      but considerable variation for dry residue, Mg, Na, K, Ca, Mg, HCO3, Cl, and SO4.
      Identification labels showed varying compliance with the Lebanese Standards
      Institution standards of identity.

PMID- 20148364
TI  - Quat-2L: a web-server for predicting protein quaternary structural attributes.
AB  - By hybridizing the functional-domain and sequence-correlated pseudo amino acid
      composition approaches, a 2-layer predictor called "Quat-2L" was developed for
      predicting the quaternary structural attribute of a protein according to its
      sequence information alone. The 1st layer is to identify the query protein as
      monomer, homo-oligomer, or hetero-oligomer. If the result thus obtained turns out
      to be homo-oligomer or hetero-oligomer, then the prediction will be automatically
      continued to further identify it belonging to one of the following six subtypes:
      (1) dimer, (2) trimer, (3) tetramer, (4) pentamer, (5) hexamer, and (6) octamer.
      The overall success rate of Quat-2L for the 1st layer identification was 71.14%;
      while the overall success rates of the 2nd layer for homo-oligomers and hetero
      oligomers were 76.91 and 82.52%, respectively. These rates were derived by the
      jackknife cross-validation tests on the stringent benchmark data set in which
      none of proteins has >= 60% pairwise sequence identity to any other in the same
      subset. As a web-server, Quat-2L is freely accessible to the public via
      http://icpr.jci.jx.cn/bioinfo/Quat-2L, where one can get 2-level results in about
      15 s.

PMID- 20148365
TI  - Preoperative imaging in renal masses: does size on computed tomography correlate
      with actual tumor size?
AB  - OBJECTIVE: To evaluate the discrepancy between tumor sizes determined from
      preoperative computed tomography (CT) and surgical specimens and its clinical
      implications. MATERIAL AND METHOD: The charts of 86 patients who underwent
      surgical resection of a renal mass between 1995 and 2007 were reviewed
      retrospectively. Tumor size was determined both from preoperative CT and
      pathologic specimen. Histopathologic evaluation was done. Wilcoxon test was used
      to compare the mean radiographic tumor size on CT with the mean pathologic size.
      P < 0.05 was considered as the threshold for statistical significance. RESULTS:
      The median age was 59 (21-84). Clinical stage was T1a in 13, T1b in 47, and >= T2
      in 26; pathologic stage was T1a in 12, T1b in 45, and >= T2 in 29 patients.
      Histological subtype was clear cell, papillary, chromophobe, sarcomatoid, and
      oncocytic in 72, 7, 5, 1, and 1 patients, respectively. Mean radiographic and
      pathologic size was 6.33 and 6.43 cm, respectively (p = 0.342). On the average,
      radiographic measurement underestimated pathologic size by 1 mm. When subgroups
      of patients according to tumor size were formed as < 4, 4-7, and > 7 cm, mean
      radiographic size was 2.79, 5.44, and 9.57 cm, mean pathologic size was 3.47,
      5.62, and 9.26 cm, respectively. In subgroups of < 4, 4-7, and > 7 cm;
      radiographic measurement underestimated pathologic size by 0.68 (p = 0.018) and
      0.18 cm (p = 0.470) and overestimated by 0.31 cm (p = 0.454), respectively.
      CONCLUSION: Overall discrepancy between radiographic and pathologic tumor sizes
      was 1 mm. No significant stage shift due to measurement error was detected. Our
      findings suggest that CT is an accurate method with which to estimate renal tumor
      size preoperatively.

PMID- 20148366
TI  - Cardiac resynchronization therapy; the importance of evaluating cardiac
      metabolism.

PMID- 20148367
TI  - Trans fatty acids in human milk are an indicator of different maternal dietary
      sources containing trans fatty acids.
AB  - The trans fatty acid (TFA) patterns in the fats of ruminant meat and dairy
      products differ from those found in other (processed) fats. We have evaluated
      different TFA isomers in human breast milk as an indicator of dietary intake of
      ruminant and dairy fats of different origins. Breast milk samples were collected
      1 month postpartum from 310 mothers participating in the KOALA Birth Cohort Study
      (The Netherlands). The study participants had different lifestyles and consumed
      different amounts of dairy products. Fatty acid methyl esters were determined by
      GC-FID and the data were evaluated by principal component analysis (PCA),
      ANOVA/Post Hoc test and linear regression analysis. The two major principal
      components were (1) 18:1 trans-isomers and (2) markers of dairy fat including
      15:0, 17:0, 11(trans)18:1 and 9(cis),11(trans)18:2 (CLA). Despite similar total
      TFA values, the 9(trans)18:1/11(trans)18:1-ratio and the
      10(trans)18:1/11(trans)18:1-ratio were significantly lower in milk from mothers
      with high dairy fat intake (40-76 g/day: 0.91 +/- 0.48, P < 0.05) compared to low
      dairy fat intake (0-10 g/day: 1.59 +/- 0.48), and lower with strict organic meat
      and dairy use (>90% organic: 0.92 +/- 0.46, P < 0.05) compared to conventional
      origin of meat and dairy (1.40 +/- 0.61). Similar results were obtained for the
      10(trans)18:1/11(trans)18:1-ratio. We conclude that both ratios are indicators of
      different intake of TFA from ruminant and dairy origin relative to other
      (including industrial) sources.

PMID- 20148369
TI  - RPE angle effects in young and middle-aged adults.
AB  - The purpose of this study was to examine contraction intensity and arm abduction
      angle effects on perceived exertion between healthy young (n=14) and middle-aged
      (n=13) adults. Subjects participated in three separate experimental sessions
      during which, maximal (MVC) and sub-maximal (10-90% MVC, 10% increments, random
      order) arm abduction contractions were performed at one of the following randomly
      assigned angles: 30, 60 and 90 degrees Perceived exertion was sampled with a
      modified Borg category-ratio scale following each sub-maximal contraction.
      Voluntary arm abduction torque was significantly (p<0.05) greatest at 30 degrees
      , as compared to 60 degrees and 90 degrees , while no significant differences
      were observed between the young and middle-aged adults. Perceived exertion was
      significantly (p<0.05) greatest at 90 degrees abduction, as compared to 30
      degrees and 60 degrees , and was not different between the two age groups. Power
      function modeling revealed that perceived exertion was significantly (p<0.05) fit
      to negatively accelerating non-linear trends for the middle-aged adults at all
      arm angles and at 90 degrees for the young adults. The findings demonstrated
      greater ratings of perceived exertion at elevated arm positions, while middle
      aged adults displayed a non-linear contraction intensity dependency at the lower
      arm elevation angles.

PMID- 20148368
TI  - Combined oral anticoagulants and antiplatelets: benefits and risks.
AB  - Combined antiplatelet and anticoagulant therapy has been suggested for those
      clinical conditions in which conventional antithrombotic regimens have shown
      suboptimal efficacy, and in patients with indication for both: antiplatelet and
      anticoagulant therapy. Clinical trials aimed at assessing the clinical benefit of
      the association with respect to mono-therapy have been conducted in patients with
      atrial fibrillation, in patients with recent myocardial infarction, and in
      patients with prosthetic heart valves. Overall, a favorable benefit-risk profile
      of combined therapy in comparison to anticoagulant alone has been observed in
      patients with mechanical prosthetic heart valves and in those with coronary
      artery disease while no clear advantage has been shown in patients with atrial
      fibrillation. In almost all these studies, however, a higher risk of major
      bleeding has been observed in patients receiving combined therapy in comparison
      to patients receiving warfarin alone. Thus, a combined regimen of anticoagulant
      and antiplatelet therapy should be reserved for selected patients at high risk of
      thromboembolic events who have a low risk of bleeding.

PMID- 20148370
TI  - Speed trends of major cycling races: does slower mean cleaner?
AB  - Since doping improves athletic performance, anti-doping policies should have the
      opposite effect. This analysis examined whether changes in the speed of major
      cycling races reflect recent anti-doping efforts. Average speeds of 5 (th) place
      finishers of the Tour de France, Giro d'Italia, and Vuelta a Espana cycling races
      were obtained for the period 1990-2009. Between 1990 and 2004, the average speed
      had been increasing by 0.16 km/h per year (p<0.001). In a downturn, since 2004,
      the average speed has decreased by 0.22 km/h per year (p=0.031). The slowing down
      of professional cycling races is compatible with the hypothesis that recent anti
      doping efforts in professional cycling have curbed the use of performance
      enhancing substances.

PMID- 20148371
TI  - ACE and ACTN3 genes and muscle phenotypes in nonagenarians.
AB  - We studied the association of ACE and ACTN3 polymorphisms with skeletal muscle
      phenotypes (i. e. upper and lower body muscular strength and functional tests) in
      Spanish nonagenarian subjects [n=41, 33 women, 8 men, age: 90-97 years]. Mean
      values of the study phenotypes were not significantly different (all P>0.05)
      between ACE and ACTN3 genotypes. The analyses of the combined effects between
      genotypes ( ACE DD & ACTN3 RR/RX vs. ACE II/ID & ACTN3 XX) did not yield any
      significant difference. Our data suggest that, in the elderly, the influence of
      genetic factors on muscle phenotype traits is not reducible to a few single
      polymorphisms, including ACE and ACTN3 variants.

PMID- 20148372
TI  - Comparative effects of caffeine and albuterol on the bronchoconstrictor response
      to exercise in asthmatic athletes.
AB  - The main aim of this study was to evaluate the comparative and additive effects
      of caffeine and albuterol (short-acting beta (2)-agonist) on the severity of EIB.
      Ten asthmatic subjects with EIB (exercise-induced bronchoconstriction)
      participated in a randomized, double-blind, double-dummy crossover study. One
      hour before an exercise challenge, each subject was given 0, 3, 6, or 9 mg/kg of
      caffeine or placebo mixed in a flavored sugar drink. Fifteen minutes before the
      exercise bout, an inhaler containing either albuterol (180 microg) or placebo was
      administered to each subject. Pulmonary function tests were conducted pre- and
      post-exercise. Caffeine at a dose of 6 and 9 mg/kg significantly reduced (p<0.05)
      the mean maximum % fall in post-exercise FEV (1) to -9.0+/-9.2% and -6.8+/-6.5%
      respectively compared to the double-placebo (-14.3+/-11.1%) and baseline (-18.4+/
      7.2%). There was no significant difference (p>0.05) in the post-exercise % fall
      in FEV (1) between albuterol ( PLUS CAFFEINE PLACEBO) (-4.0+/-5.2%) and the 9
      mg/kg dose of caffeine (-6.8+/-6.5%). Interestingly, there was no significant
      difference (p>0.05) in the post-exercise % fall in FEV (1) between albuterol (
      PLUS CAFFEINE PLACEBO) (-4.0+/-5.2%) and albuterol with 3, 6 or 9 mg/kg of
      caffeine (-4.4+/-3.8, -6.8+/-5.6, -4.4+/-6.0% respectively). Similar changes were
      observed for the post-exercise % fall in FVC, FEF (25-75%) and PEF. These data
      indicate that moderate (6 mg/kg) to high doses (9 mg/kg) of caffeine provide a
      significant protective effect against EIB. It is feasible that the negative
      effects of daily use of short-acting beta (2)-agonists by asthmatic athletes
      could be reduced simply by increasing caffeine consumption prior to exercise.

PMID- 20148373
TI  - Diurnal and exercise-related variability of haemoglobin and reticulocytes in
      athletes.
AB  - Haemoglobin (Hb) and Reticulocytes (Ret) are measured as indirect markers of
      doping in athletes. We studied the diurnal variation, the impact of exercise,
      fluid intake and ambient temperature in athletes on these parameters. Hourly
      venous blood samples were obtained from 36 male athletes of different disciplines
      (endurance (END) and non-endurance (NON-END)) over 12 h during a typical training
      day. Seven inactive subjects served as controls (CON). Hb and Ret were
      determined. A mixed model procedure was used to analyse the data. At baseline, Hb
      was similar for all groups, END showed lower Ret than NON-END and CON. Exercise
      showed a significant impact on Hb (+0.46 g/dl, p<0.001), the effect disappeared
      approximately 2 h after exercise. Hb decreased over the day by approximately 0.55
      g/dl (p<0.01). There was no relevant effect on Ret. Fluid intake and ambient
      temperature had no significant effect. Hb shows significant diurnal- and exercise
      related variations. In an anti-doping context, most of these variations are in
      favour of the athlete. Blood samples taken after exercise might therefore provide
      reliable results and thus be used for the longitudinal monitoring of athletes if
      a timeframe for the re-equilibration of vascular volumes is respected.

PMID- 20148374
TI  - Glenoid labral repair in Major League Baseball pitchers.
AB  - Little is known about outcomes of glenoid labral repair in Major League Baseball
      (MLB) pitchers. We hypothesized that following repair, pitching performance would
      not be significantly different from an uninjured cohort. Fifty-one pitchers were
      identified who pitched in at least one MLB game prior to undergoing isolated
      glenoid labral repair. For the three years prior to and following surgery,
      demographic and performance variables were analyzed for an association with
      labral injury and repair, and compared to a control cohort of MLB pitchers
      without history of repair. Following surgery, 72.5% of pitchers returned to MLB
      at a mean of 13.1 months with no significant change in performance. Starting
      pitchers had a higher risk of labral injury requiring repair (p< or =0.05).
      Pitchers that returned to play averaged more innings pitched in the seasons prior
      to surgery and had a higher body mass index than those that did not return to
      play (p< or =0.05). Approximately 70% of MLB pitchers undergoing labral repair
      can be expected to return to competition postoperatively with no significant
      change in performance. Starting pitchers are more likely to undergo repair, but
      pitchers with greater preoperative innings pitched per season have a greater
      likelihood of returning to play.

PMID- 20148375
TI  - Risk behaviors for eating disorders in Brazilian dancers.
AB  - This study investigated the frequency of risk behaviors for eating disorders and
      their association with anthropometric, demographic, and socioeconomic variables
      in Brazilian professional dancers. Portuguese-language versions of the Eating
      Attitudes Test and of the Bulimic Investigatory Test, Edinburgh (BITE) were
      applied to 39 female and 22 male dancers considered to be some of the best
      classical ballet performers in Brazil. Prevalence ratios (PR) and 95% confidence
      intervals (CI) were estimated. Risk behaviors for eating disorders were observed
      in 31% of the dancers. Those who had a percentage of body fat above (PR=4.04; 95%
      CI=1.42-11.47) or below (PR=3.57; 95% CI=1.04-12.24) what is considered normal
      for the profession, and those who lived alone (PR=3.13; 95% CI=1.16-8.48)
      presented higher risk for eating disorders. In conclusion, the frequency of risk
      behaviors for eating disorders among the Brazilian dancers was high, which seems
      to be associated with the physical requirements of the profession. Those who are
      outside the BF% expected for dancers and those who live alone are the groups most
      vulnerable to developing eating disorders, and thus are the ones which are most
      in need of receiving special attention in regard to the intervention measures.

PMID- 20148376
TI  - Gender and contraction mode on perceived exertion.
AB  - The purpose of this study was to examine perceived exertion responses during
      concentric and eccentric elbow flexor contractions between young adult men and
      women. Thirty healthy young adults participated in two experimental sessions.
      During the first session, subjects performed five concentric isokinetic maximal
      voluntary contractions (MVC) of elbow flexion, followed by nine, randomly-ordered
      sub-maximal contractions (10-90% MVC). The same procedures were repeated during
      the second session, with the exception that eccentric contractions were
      performed. Subjects rated their perceived exertion following the sub-maximal
      contractions with the Borg category-ratio scale. Perceived exertion was
      significantly (p<0.05) less than equivalent values on the CR-10 scale at
      intensities greater than, and equal to, 30% MVC. A three-factor interaction
      between 30-40% MVC indicated that perceived exertion increased more during the
      eccentric, than concentric, contractions in women, while the opposite pattern was
      evident for the men. There were no significant contraction mode or gender
      differences. Power function modeling revealed that perceived exertion increased
      in a negatively accelerating manner, except for the men performing eccentric
      exercise. Perceived exertion increases in a similar non-linear manner between men
      and women during concentric contractions, while men exhibited a statistically
      linear pattern during eccentric contractions.

PMID- 20148377
TI  - Prevalence and incidence of endocrine disorders in children: results of a survey
      in Baden-Wuerttemberg and Bavaria (EndoPrIn BB) 2000-2001.
AB  - BACKGROUND: Sparse data is available on the incidence of endocrine disorders
      among children in Germany. AIM: A pioneer study was established to analyse, in
      the German states of Baden-Wuerttemberg (BW) and Bavaria (BY), the incidence and
      prevalence of congenital adrenal hyperplasia (AGS; CAH), precocious puberty (PP),
      primary congenital hypothyreosis (PCH), Graves disease (MB), and growth disorders
      related to the Ullrich-Turner syndrome (UTS) and growth hormone deficiency (GHD).
      METHODS: Participation in the study involved each paediatric hospital in BW and
      BY (n = 63),and all regional paediatricians belonging to the Association of
      Statutory Health Insurance Physicians (SHI) practising in these states (n = 1
      443). Data collection was done from January 1, 2000, to December 31, 2001, and
      included all patients in the 0- < 18 age range. RESULTS: Completeness of data was
      81 % for CAH and 55 % for UTS (capture-mark-recapture method).The incidence rate
      (IR, per 100 000 / year)versus prevalence rate (per 100 000 at the time point
      December 31, 2001) was: CAH 0.64 vs.9.60; PP 2.42 vs. 10,85; PCH 1.88 vs. 14.97;
      MB 0.89 vs. 3.25; UTS 2.15 vs. 29.07; and GHD 3.47(IR). Among neonates, the
      incidence of CAH was 1 / 7 794; PCH 1 / 2 629 and UTS 1 / 2 300. CONCLUSIONS: A
      pioneer study has been established in Germany for investigating the frequency of
      AGS (CAH), PP, PCH, MB, UTS, and GHD among children and adolescents. Our data
      shows that these disorders occur in approx. 2,700 children per year in total
      Germany, and about 12 000 of these children need to be treated in specialized
      paediatric endocrinological centres.

PMID- 20148378
TI  - [Public attitudes towards alcohol dependence].
AB  - OBJECTIVE: Although among the most prevalent psychiatric conditions, alcoholism
      seems to be neglected within the current debate on mental illness stigma. We
      establish the state of current research on public attitudes towards alcohol
      dependent people. METHODS: In an extensive search of the literature, we
      identified 49 population studies on this topic between 1948 and 2008. 27 studies
      contained relevant information from Western countries and were included in this
      review. RESULTS: Although most people regard alcoholism as an illness, there is a
      strong tendency to blame those affected for their condition. Psycho-social causal
      attributions prevail over biologic explanations. Most people regard alcohol
      dependent persons as unpredictable and dangerous. The desire for social distance
      is stronger towards alcohol dependent persons than towards those with other
      psychiatric diagnoses such as depression or schizophrenia; only those addicted to
      illegal drugs suffer stronger rejection. Preferences of the public for resource
      allocation within the health care system put alcohol dependent patients at a
      potential disadvantage. CONCLUSIONS: Alcoholism is a severely stigmatized
      condition. In order to change the stigma of alcoholism, studies exploring
      theoretical models and mechanisms of stigmatization seem necessary.

PMID- 20148379
TI  - [Trauma and psychosis in german psychiatry - a historical analysis].
AB  - OBJECTIVE: The paper reports an historical analysis of the debate on trauma and
      psychosis in German psychiatry. METHODS: Content analysis of five leading German
      psychiatric journals between 1889 and 2005. RESULTS: A substantial number of
      publications until the late 1960s addressed different aspects of potential links
      between trauma and subsequent psychosis. Papers exclusively focused on traumatic
      experience in adulthood. Most papers showed a negative attitude towards the idea
      of traumatic experiences causing psychosis. CONCLUSIONS: The debate on
      psychological trauma and psychosis refers to a long tradition in German
      psychiatry. Whilst the discussion contributed significantly to concepts and
      classifications of psychotic illnesses, it did not generate a coherent model for
      the potential association of trauma and subsequent psychotic disorder.

PMID- 20148380
TI  - [Evaluation of a residential care and supported housing program in the regional
      association of Westphalia-Lippe].
AB  - OBJECTIVE: During the deinstitutionalisation of psychiatric care in Germany, new
      psychiatric care approaches have been developed, which have been rarely
      scientifically evaluated. This study aims at evaluating the residential care and
      supported housing program of a public service in Westphalia, Northwestern
      Germany. METHODS: Data on 1486 clients about sociodemographics, individual
      biographies, housing, social integration and perspective of care were collected
      by staff. Individual interviews on the clients' quality of life were conducted
      with 941 subjects. RESULTS: The residential care and supported housing program
      clients are chronically mentally ill and disabled. Clients from the supported
      housing sector have a much more favorable biographical and social background
      compared to those from residential care. Integration into the regular workforce
      does usually not happen. Clients from the residential care sector have only few
      social contacts outside their institution. The quality of life assessment
      revealed no differences between the settings. CONCLUSIONS: More external social
      contacts should be provided especially for the residential care clients.
      Motivational interventions might enhance the clients' social inclusion further.

PMID- 20148381
TI  - [Prognostic factors from a long-term follow-up of heroin-assisted treatment in
      Switzerland 1994-2007].
AB  - OBJECTIVE: To identify prognostic factors for a positive or negative termination
      of heroin-assisted treatment (HAT) in Switzerland. METHOD: A complete census of
      all 3155 patients ever admitted was analysed using the proportional hazard model
      (including time dependent covariates). RESULTS: Median length of stay was 11.4
      years; the maximal length of stay was 13.9 years. 299 positive and 463 negative
      terminations were registered. Terminations clustered in the first year. Both time
      to positive and negative termination was significantly dependent on historical
      treatment cohorts since 1994. Positive termination was negatively associated with
      treatment in larger treatment centres (OR: 0.77, CI: 0.61-0.97) and positively
      with income from the social system (OR: 1.33; CI: 1.03-1.72). Negative
      terminations were positively associated with HIV infection before treatment (OR:
      1.74; CI: 1.40-2.16), delinquence (OR 1.36; CI: 1.09-1.69), and higher levels of
      distrust (OR: 1.18 per scoring point; CI = 1.05-1.31). CONCLUSIONS: Length of
      stay in Swiss HAT is considerable. The proportion of positive terminations did
      not increase with longer stays, indicating that the majority of patients are in
      chronic palliative care. Negative terminations outweighed positive terminations,
      with a low predictive power from co-variates. The routine assessment and analysis
      of different covariates, such as indicators of treatment process, has the
      potential to improve the therapeutic outcomes of HAT.

PMID- 20148382
TI  - [Off-label use of acetazolamide in a patient with familial hemiplegic migraine
      and concomitant psychotic episodes].
AB  - A 42-year-old patient with cognitive deficits due to childhood meningitis
      suffered from recurrent episodes of familial hemiplegic migraine. Additionally,
      he developed concomitant psychotic episodes requiring subsequent in-patient
      psychiatric treatment. Following combined neurological and psychiatric treatment
      he always recovered from the episodes within a few weeks time. Prophylactic
      treatment of migraine using topiramate and acetazolamide (off-label) prevented
      attacks for several months. When off-label compensation was refused and, as a
      consequence, the drug discontinued, hemiplegia relapsed within a few days. Hence,
      acetazolamide was prescribed again and the family paid for the medication. Since
      that time, the patient did not show severe attacks for at least 8 months apart
      from a transient attack induced by acute flu-like illness.

PMID- 20148384
TI  - [Maturation of the autonomic nervous system: differences in heart rate
      variability at different gestational weeks].
AB  - AIMS: Heart rate variability (HRV) reveals information on the functional state of
      the autonomic nervous system (ANS). This study was initiated to assess the
      physiological and maturational development of the ANS by comparing HRV data of a
      large number healthy foetus of different gestational ages from the 24(th) to the
      42(nd) week. METHODS: Cardiotocogram (CTG) recordings of HRV of 172 healthy
      foetus (24-42 weeks' gestation) were performed to establish normative data.
      Frequency domain HRV parameters were computed in three frequency bands. RESULTS:
      The gestational ages of the foetuses correlate with HRV. Lower gestational age in
      weeks showed lower frequency domain parameters than higher gestational age in
      weeks. The most significant differences were discerned for HRV parameters
      reflecting sympathetic activity in LF (low frequency) and VLF (very low
      frequency), due to the adrenergic system. CONCLUSIONS: Maturation of the ANS is
      accompanied by increasing HRV with a pronounced increase of sympathetic activity.
      These changes are measurable by CTG recordings with a computer algorithm which
      can calculate short-term variability on the basis of CTG data. Problems of the
      CTG signal, as shown before, were the parameters of the time domain, which could
      only be well detected by ECG or foetal magnetocardiography (FMCG).

PMID- 20148385
TI  - [Sociodemography of primiparae and multiparae in a population-based survey--the
      Survey of Neonates in Pomerania (SNiP)].
AB  - BACKGROUND: The official birth statistics are regarded as a reliable data source
      on births and birth rate in the German population. However, they show
      methodological limitations with respect to the identification of first-time
      mothers and the number of children per mother. The mothers' social and economical
      background is not assessed. The goal of the present analysis was (a) to describe
      demographic and socio-economic variables of all births in a defined region over a
      fixed time-frame and (b) to make a comparison on the basis of parity and
      gravidity. METHOD: From 2004-2007 4,982 children were born in the region and data
      from n=4,788 children were assessed (96%); n=3,505 (73%) of these mothers
      consented to a more detailed assessment. RESULTS: The fertility rate in the SniP
      region is low. There are fewer children per 1,000 women and born per women in
      general. The average age of primiparae was 25 and 26 years. As can be expected
      there is a significant difference between primiparae and multiparae with respect
      to age. There is also a difference in occupational status. 17% of the primiparae
      have been multigravidae. CONCLUSIONS AND DISCUSSION: For the first time in
      Germany, the SNiP collected comprehensive population-based data on the age and
      socio-demographic variables of children and their mothers in a defined
      geographical region. A significant discrepancy for average age of primiparae
      between the study results and the official statistics is discussed in the light
      of methodological and regional issues. Our results require the continuation of
      comprehensive population-based data assessment. Furthermore, the SniP region
      could serve as a model region for future research. In international comparisons
      Germany's reproductive behaviour has proved to be unfavourable, which is
      accentuated in the region under examination.

PMID- 20148386
TI  - [Short communication about percentile values of body measures of newborn babies].

PMID- 20148388
TI  - Target validation and ligand development for a pathogenic fungal profilin, using
      a knock-down strain of pathogenic yeast Candida glabrata and structure-based
      ligand design.
AB  - The emergence of antifungal drug resistance is triggering vigorous searches for
      novel antifungal targets and lead compounds. In this study, we focused on fungal
      profilin, which is a small actin control protein sharing limited homology to
      human profilin. To validate its potentiality as a target, a profilin-conditional
      mutant of the pathogenic yeast Candida glabrata was constructed, using a
      regulatable Tet promoter, and its growth was monitored in vitro. Repression of
      profilin expression led to severe growth defect, demonstrating the potential of
      this protein as a novel antifungal target. Next, novel peptides binding to the
      active interface of profilin were designed by computer simulation. ELISA analysis
      showed that these peptides did bind to the wild-type profilin but bound less
      strongly to a profilin with amino acid substitutions at the active interface.
      Hence, we show here that profilin is a potential antifungal target and offer
      novel peptide ligands.

PMID- 20148387
TI  - A functional analysis of Kluyveromyces lactis glutathione reductase.
AB  - Glutathione reductase (GLR) null mutants of the yeast Kluyveromyces lactis, a
      model eukaryotic respiratory cell, were created and phenotypically analysed. We
      found that cells lacking GLR show decreased resistance to oxidative stress and
      higher levels of reactive oxygen species and catalase activity than the wild-type
      strain. However, glutathione redox levels (GSH : GSSG ratio) were similar in the
      DeltaKlglr1 mutant and wild-type strains. The thioredoxin-thioredoxin reductase
      system is proposed as an alternative system for maintaining the GSH : GSSG ratio
      in the DeltaKlglr1 mutant. The involvement of GLR in glucose metabolism in K.
      lactis is suggested by the improved growth on glucose caused by the DeltaKlglr1
      mutation and by the increased GLR activity in the DeltaKlgcr1 strain, KlGcr1
      being a transcriptional activator of glycolytic genes. We also studied the
      subcellular location of GLR in K. lactis, showing that it is present in
      mitochondria; however, the DeltaKlglr1 mutation does not affect mitochondrial
      morphology. Genomic DNA integrity and life span are also unaffected by the
      DeltaKlglr1 mutation, at least under the conditions tested in this study.

PMID- 20148389
TI  - Efficient vectors for expression cloning of large numbers of PCR fragments in P.
      pastoris.
AB  - The yeast vectors described, pYEV and pYEVB, were designed for parallel
      polymerase chain reaction (PCR) cloning of open reading frames (ORFs) and
      immediate protein expression in Pichia pastoris. The pYEV vector was used to
      clone PCR fragments obtained by using Taq or similar polymerase mixes, which
      leave an A-base overhang. The other vector pYEVB, with the same features for
      blunt-end ligation of PCR products, was developed to be complementary to pYEV.
      These two plasmids were linearized using the restriction enzymes BfuI and SchI,
      respectively. The purified PCR products, without any other treatments, were
      cloned into the linearized vectors, followed by selection on plates supplemented
      with X-gal. Only desired recombinants carrying the target gene in the correct
      orientation can give typical blue colonies. This screening technique is based on
      a lacO reconstruction strategy that can produce a full-length lacO to exhaust
      endogenous LacI and switch on the transcription of lacZ in the host. The
      recombinant plasmids extracted from the blue colonies can be linearized by SalI
      and transformed into P. pastoris for immediate expression. By using these two
      vectors, researchers could be saved from the tedious and time-consuming
      conventional cloning procedures.

PMID- 20148390
TI  - New applications of pHluorin--measuring intracellular pH of prototrophic yeasts
      and determining changes in the buffering capacity of strains with affected
      potassium homeostasis.
AB  - pHluorin is a pH-sensitive variant of green fluorescent protein for measuring
      intracellular pH (pH(in)) in living cells. We constructed a new pHluorin plasmid
      with the dominant selection marker KanMX. This plasmid allows pH measurements in
      cells without auxotrophic mutations and/or grown in chemically indefinite media.
      We observed differing values of pH(in) for three prototrophic wild-types. The new
      construct was also used to determine the pH(in) in strains differing in the
      activity of the plasma membrane Pma1 H(+)-ATPase and the influence of glucose on
      pH(in). We describe in detail pHluorin measurements performed in a microplate
      reader, which require much less hands-on time and much lower cell culture volumes
      compared to standard cuvettes measurements. We also utilized pHluorin in a new
      method of measuring the buffering capacity of yeast cell cytosol in vivo, shown
      to be ca. 52 mM/pH for wild-type yeast and moderately decreased in mutants with
      affected potassium transport.

PMID- 20148391
TI  - The Yap family and its role in stress response.
AB  - The budding yeast Saccharomyces cerevisiae possesses a very flexible and complex
      programme of gene expression when exposed to several environmental challenges.
      Homeostasis is achieved through a highly coordinated mechanism of transcription
      regulation involving several transcription factors, each one acting singly or in
      combination to perform specific functions. Here, we review our current knowledge
      of the function of the Yap transcription factors in stress response. They belong
      to b-ZIP proteins comprising eight members with specificity at the DNA-binding
      domain distinct from that of the conventional yeast AP-1 factor, Gcn4. We finish
      with new insights into the links of transcriptional networks controlling several
      cellular processes. The data reviewed in this article illustrate how much our
      comprehension of the biology of Yap family involved in stress response has
      advanced, and how much research is still needed to unravel the complexity of the
      role of these transcriptional factors. The complexities of these regulatory
      interactions, as well as the dynamics of these processes, are important to
      understand in order to elucidate the control of stress response, a highly
      conserved process in eukaryotes.

PMID- 20148392
TI  - Feelings of insecurity: review of attachment and eating disorders.
AB  - OBJECTIVE: Attachment theory has received increasing attention from clinicians
      and researchers in the field of eating disorders. This paper is an updated review
      on theoretical approaches in the field, and of studies employing the Adult
      Attachment Interview. METHOD: We searched the major databases such as PsycInfo
      and Science Direct for empirical and theoretical studies on attachment and eating
      disorders, and these are reviewed. RESULTS: Theoretical approaches on attachment
      and eating disorders highlight either retrospective, general risk or attachment
      theoretical statements. There is greater prevalence of insecure attachment in the
      eating disordered population than in non-clinical samples. However, there is no
      sufficient evidence to conclude about specific mechanisms for this connection.
      DISCUSSION: The theoretical approaches vary in their theoretical grounding,
      specificity and empirical support. AAI-based research on attachment and eating
      disorders is still at an early stage. More advanced studies are required for the
      field to move forward.

PMID- 20148393
TI  - Editorial note.

PMID- 20148394
TI  - Commentary. From shock therapy to psychotherapy: the role of Peter Dally in the
      revolutions of anorexia nervosa treatment.

PMID- 20148395
TI  - Binge eating disorder in a Chinese male--a case report.
AB  - OBJECTIVE: There are reports in China about males suffering from anorexia nervosa
      and bulimia nervosa, but hitherto no report of binge eating disorder (BED).
      METHOD: This case report describes the history, symptom progression and treatment
      of a male suffering from BED. RESULTS: Many Chinese people who come from rural
      areas try to integrate in the urban life. Regardless of their level of education
      many suffer various difficulties, which can trigger psychological disorders.

PMID- 20148396
TI  - PANDAS and anorexia nervosa--a spotters' guide: suggestions for medical
      assessment.
AB  - OBJECTIVE: Pediatric Autoimmune Neuropsychiatric Disorders Associated with
      Streptococcal infection (PANDAS) should be considered in sudden onset,
      prepubertal Anorexia Nervosa (AN), arising shortly after an apparent
      streptococcal infection. However, the absence of a specific biological marker of
      PANDAS renders the diagnosis difficult. This paper critically reviews available
      tests for PANDAS and recommends a standardized approach to its investigation.
      METHOD: Medline database review between 1990 and 2008. RESULTS: Existing tests
      may be categorized as: (i) Non-specific markers of inflammation or immune
      response (Erythrocyte sedimentation rate, ESR; C-reactive protein, CRP;
      Neopterin), (ii) specific markers of streptococcal infection (throat swab and
      anti-streptococcal antibodies, Anti-streptolysin, ASO; Antideoxyribonuclease B,
      antiDNaseB), (iii) non-specific markers of auto-immune reaction (Antineuronal
      antibodies, AnAb; D8/17). No one test reliably identifies PANDAS. The lack of
      specificity and methodological problems may lead to errors of diagnosis.
      DISCUSSION: When PANDAS-Anorexia Nervosa (PANDAS-AN) is suspected clinically we
      recommend conducting all the above investigations. The more positive results
      there are the more likely is the diagnosis, but particular weighting should be
      given to AnAb and D8/17.

PMID- 20148397
TI  - Spontaneous pneumomediastinum in anorexia nervosa: a case report and review of
      the literature on pneumomediastinum and pneumothorax.
AB  - We report a case of a 20-year-old white woman with the history of anorexia
      nervosa presenting with spontaneous pneumomediastinum (SPM). On admission, her
      body mass index (BMI) was 9.9 kg/m(2). Physical examination revealed subcutaneous
      crepitation especially in the axillae, the intercostal spaces, between the
      scapulae and along the spine. A chest X-ray showed extensive tissue emphysema,
      especially in the upper mediastinum. In a computed tomography (CT) scan,
      additional air was found in the upper retroperitoneal space adjacent to the
      stomach and to the left of the aorta. The patient recovered clinically within
      three weeks, and a CT scan showed a complete remission of the pneumomediastinum
      and subcutaneous emphysema. Based on this, case review of the literature about
      the frequency of pneumomediastinum in young patients with low weight is presented
      concerning epidemiology, etiology, symptoms, diagnosis, treatment, time to
      recovery and prognosis.

PMID- 20148398
TI  - Lighting up lumps.

PMID- 20148399
TI  - Inhibitory effects of curcumenol on human liver cytochrome P450 enzymes.
AB  - Curcumenol, one of the major components of Zedoary turmeric oil, has been widely
      used to treat cancer and inflammation. As an antibiotic or anticancer drug,
      curcumenol is highly likely to be used in combination with various synthetic
      drugs in most cases, thus it is necessary to evaluate potential pharmacokinetic
      drug-drug interactions induced by curcumenol. In this study, the inhibitory
      effects of curcumenol on seven CYP isoforms were investigated, and the results
      demonstrated that only CYP3A4 was strongly inhibited (IC(50) = 12.6 +/- 1.3
      microM). Kinetic analysis showed the inhibition type was competitive with K(i)
      value of 10.8 microM. Time- and NADPH-dependent inhibitions were also
      investigated to show curcumenol is not a mechanism-based inhibitor. Employing
      these in vitro data and maximum plasma concentration of curcumenol in human
      predicted from beagle dog's in vivo pharmacokinetic data, the change in AUC of
      victim drugs was predicted to be 0.4%, which suggested that curcumenol may be
      safely used without inducing metabolic drug-drug interaction through P450
      inhibition. Nevertheless, due to the limited pharmacokinetic data available for
      curcumenol in humans, it is still not possible to evaluate its potential clinical
      effects on human patients from in vitro data. Thus, the magnitude of drug-drug
      interaction (DDI) induced by curcumenol warrants further investigation.

PMID- 20148400
TI  - Integrated single-cell analysis shows Pichia pastoris secretes protein
      stochastically.
AB  - The production of heterologous proteins by secretion from cellular hosts is an
      important determinant for the cost of biotherapeutics. A single-cell analytical
      method called microengraving was used to examine the heterogeneity in secretion
      by the methylotrophic yeast Pichia pastoris. We show that constitutive secretion
      of a human Fc fragment by P. pastoris is not cell-cycle dependent, but rather
      fluctuates between states of high and low productivity in a stochastic manner.

PMID- 20148401
TI  - Dynamic gene expression regulation model for growth and penicillin production in
      Penicillium chrysogenum.
AB  - As is often the case for microbial product formation, the penicillin production
      rate of Penicillium chrysogenum has been observed to be a function of the growth
      rate of the organism. The relation between the biomass specific rate of
      penicillin formation (q(p)) and growth rate (mu) has been measured under steady
      state conditions in carbon limited chemostats resulting in a steady state
      q(p)(mu) relation. Direct application of such a relation to predict the rate of
      product formation during dynamic conditions, as they occur, for example, in fed
      batch experiments, leads to errors in the prediction, because q(p) is not an
      instantaneous function of the growth rate but rather lags behind because of
      adaptational and regulatory processes. In this paper a dynamic gene regulation
      model is presented, in which the specific rate of penicillin production is
      assumed to be a linear function of the amount of a rate-limiting enzyme in the
      penicillin production pathway. Enzyme activity assays were performed and strongly
      indicated that isopenicillin-N synthase (IPNS) was the main rate-limiting enzyme
      for penicillin-G biosynthesis in our strain. The developed gene regulation model
      predicts the expression of this rate limiting enzyme based on glucose repression,
      fast decay of the mRNA encoding for the enzyme as well as the decay of the enzyme
      itself. The gene regulation model was combined with a stoichiometric model and
      appeared to accurately describe the biomass and penicillin concentrations for
      both chemostat steady-state as well as the dynamics during chemostat start-up and
      fed-batch cultivation.

PMID- 20148402
TI  - Collapse temperature of solutions important for lyopreservation of living cells
      at ambient temperature.
AB  - In this study, the collapse temperature was determined using the freeze-drying
      microscopy (FDM) method for a variety of cell culture medium-based solutions
      (with 0.05-0.8 M trehalose) that are important for long-term stabilization of
      living cells in the dry state at ambient temperature (lyopreservation) by freeze
      drying. Being consistent with what has been reported in the literature, the
      collapse temperature of binary water-trehalose solutions was found to be similar
      to the glass transition temperature (T'(g) approximately -30 degrees C) of the
      maximally freeze-concentrated trehalose solution (approximately 80 wt% trehalose)
      during the freezing step of freeze-drying, regardless of the initial
      concentration of trehalose. However, the effect of the initial trehalose
      concentration on the collapse temperature of the cell culture medium-based
      trehalose solutions was identified to be much more significant, particularly when
      the trehalose concentration is less than 0.2 M (the collapse temperature can be
      as low as -65 degrees C). We also determined that cell density from 1 to 10
      million cells/mL and ice seeding at high subzero temperatures (-4 and -7 degrees
      C) have negligible impact on the solution collapse temperature. However, ice
      seeding does significantly affect the ice crystal morphology formed during the
      freezing step and therefore the drying rate. Finally, bulking agents (mannitol)
      could significantly affect the collapse temperature only when trehalose
      concentration is low (<0.2 M). However, improving the collapse temperature by
      using a high concentration of trehalose might be preferred to the addition of
      bulking agents in the solutions for freeze-drying of living cells. We further
      confirmed the applicability of the collapse temperature measured with small-scale
      (2 microL) samples using the FDM system to freeze-drying of large-scale (1 mL)
      samples using scanning electron microscopy (SEM) data. Taken together, the
      results reported in this study should provide useful guidance to the development
      of optimal freeze-drying protocols for lyopreservation of living cells at ambient
      temperature for easy maintenance and convenient wide distribution to end users,
      which is important to the eventual success of modern cell-based medicine.

PMID- 20148403
TI  - Can size alone explain some of the differences in toxicity between beta-amyloid
      oligomers and fibrils?
AB  - beta-Amyloid (Abeta) peptide is believed to play a key role in the mechanism of
      Alzheimer's disease (AD). Abeta tends to aggregate to form amyloid fibrils. A
      variety of evidence indicates that Abeta aggregates are toxic in vitro and in
      vivo. An early "Abeta hypothesis" postulated that AD was the consequence of
      neuron death induced by insoluble deposits of large Abeta fibrils. Newer findings
      indicate that small soluble Abeta oligomers are the neurotoxic species, yet their
      structure is still unknown. Many researchers have tried to probe the differences
      in molecular structure between Abeta oligomers, protofibrils, and fibrils that
      give rise to their unique toxicities, but with limited success. In this report,
      we examine the hypothesis that differences in the toxicity of different
      aggregated Abeta species are the result of differences in species concentration
      and diffusivity. Using a simple mathematical analysis based on the assumption of
      a diffusion-limited reaction, we demonstrate that near 10-fold differences in
      toxicity between spherical oligomers and fibrils can be explained from size and
      concentration arguments. While this work does not suggest that Abeta oligomers
      and fibrils have identical molecular structures, it highlights the possibility
      that simple physical phenomena may contribute to the biological processes induced
      by Abeta.

PMID- 20148404
TI  - Naphthyl methacrylate-based monolithic column for RP-CEC via hydrophobic and pi
      interactions.
AB  - A neutral naphthyl methacrylate-based monolith (NMM) was introduced for RP-CEC of
      various aromatic compounds via hydrophobic and pi interactions. It was
      characterized over a wide range of elution conditions to gain insight into its RP
      retention mechanism toward the various solute probes under investigation. First,
      the NMM column exhibited cathodal EOF at various mobile phase compositions and pH
      suggesting that although the NMM column is void of fixed charges, it acquires a
      negative zeta potential. It is believed that the negative zeta potential is
      imparted by the adsorption of mobile phase ions to the NMM surface. The NMM
      column exhibited pi-pi interactions in addition to hydrophobic interactions due
      to the aromatic and nonpolar nature of its naphthyl ligands. In all cases, the
      retention of the various aromatic test solutes including PAHs, benzene
      derivatives, toluene derivatives, anilines and toluidine, tolunitrile and
      nitrotoluene positional isomers on the NMM column were compared to their
      retention on an octadecyl acrylate-based monolithic column. Not only were the
      values of the retention factors of the various solutes on the NMM column higher
      than those obtained on the octadecyl acrylate-based monolithic column under
      otherwise the same CEC conditions, but the elution orders were also different on
      both columns with a superior and unique selectivity exhibited by the NMM column.

PMID- 20148406
TI  - Acute metal stress in Populus tremula x P. alba (717-1B4 genotype): leaf and
      cambial proteome changes induced by cadmium 2+.
AB  - The comprehension of metal homeostasis in plants requires the identification of
      molecular markers linked to stress tolerance. Proteomic changes in leaves and
      cambial zone of Populus tremula x P. alba (717-1B4 genotype) were analyzed after
      61 days of exposure to cadmium (Cd) 360 mg/kg soil dry weight in pot-soil
      cultures. The treatment led to an acute Cd stress with a reduction of growth and
      photosynthesis. Cd stress induced changes in the display of 120 spots for leaf
      tissue and 153 spots for the cambial zone. It involved a reduced photosynthesis,
      resulting in a profound reorganisation of carbon and carbohydrate metabolisms in
      both tissues. Cambial cells underwent stress from the Cd actually present inside
      the tissue but also a deprivation of photosynthates caused by leaf stress. An
      important tissue specificity of the response was observed, according to the
      differences in cell structures and functions.

PMID- 20148407
TI  - Neuroprotective effect of HT008-1, a prescription of traditional Korean medicine,
      on transient focal cerebral ischemia model in rats.
AB  - HT008-1 is one of the prescriptions used in Traditional Korean Medicine for the
      treatment of mental and physical weakness. It is composed of Panax ginseng,
      Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis, which
      have been reported to have various pharmacological effects on the central nervous
      system. The study investigated whether HT008-1 has neuroprotective effects in a
      focal cerebral ischemia rat model. Stroke was induced in rats by 2 h of middle
      cerebral artery occlusion (MCAo) followed by 22 h of reperfusion. HT008-1 (30,
      100 and 300 mg/kg) and the component herbs (300 mg/kg) were administered orally
      twice at 0 and 2 h after ischemia. Oral administration of 300 mg/kg HT008-1
      reduced brain infarction by 45.7%, prolonged the latency time by 24.8% in the
      rotarod test, and enhanced the score by 17.0% in the balance beam test. Only P.
      ginseng and S. baicalensis showed protective effects, and HT008-1 showed a
      greater effect than its component herbs. HT008-1 down-regulated the COX-2 and OX
      42 expression in the penumbra region. In conclusion, the results show that HT008
      1 may be effective in a rat stroke model by an antiinflammatory mechanism and may
      improve sensory-motor function by reducing damage in the cortex and caudoputamen.

PMID- 20148408
TI  - Horse chestnut extract contracts bovine vessels and affects human platelet
      aggregation through 5-HT(2A) receptors: an in vitro study.
AB  - Extract from seeds and bark of horse chestnut (Aesculus hippocastanum L) is used
      as an herbal medicine against chronic venous insufficiency. The effect and
      mechanism of action on veins, arteries, and platelets are not fully understood.
      The aim of this study was to investigate the effects and mechanisms of action of
      horse chestnut on the contraction of bovine mesenteric veins and arteries, and
      human platelet aggregation. Contraction studies showed that horse chestnut
      extract dose-dependently contracted both veins and arteries, with the veins being
      the most sensitive. Contraction of both veins and arteries were significantly
      inhibited by the 5-HT(2A) receptor antagonist ketanserin. No effect on
      contraction was seen with the cyclooxygenase inhibitor indomethacin, the alpha(1)
      receptor antagonist prazosin or the angiotensin AT(1) receptor antagonist
      saralasin neither in veins nor arteries. ADP-induced human platelet aggregation
      was significantly reduced by horse chestnut. A further reduction was seen with
      the extract in the presence of ketanserin. In conclusion, horse chestnut
      contraction of both veins and arteries is, at least partly, mediated through 5
      HT(2A) receptors. Human platelet aggregation is reduced by horse chestnut. The
      clinical importance of these findings concerning clinical use, possible adverse
      effects, and drug interactions remains to be investigated.

PMID- 20148409
TI  - Decision making in elderly patients with severe dementia and pneumonia.

PMID- 20148410
TI  - Increased erythrocyte catechol-O-methyltransferase activity in elderly:
      relationship to clinical peculiarities in Parkinson's disease?

PMID- 20148411
TI  - Prediction of metabolic function from limited data: Lumped hybrid cybernetic
      modeling (L-HCM).
AB  - Motivated by the need for a quick quantitative assessment of metabolic function
      without extensive data, we present an adaptation of the cybernetic framework,
      denoted as the lumped hybrid cybernetic model (L-HCM), which combines the
      attributes of the classical lumped cybernetic model (LCM) and the recently
      developed HCM. The basic tenet of L-HCM and HCM is the same, that is, they both
      view the uptake flux as being split among diverse pathways in an optimal way as a
      result of cellular regulation such that some chosen metabolic objective is
      realized. The L-HCM, however, portrays this flux distribution to occur in a
      hierarchical way, that is, first among lumped pathways, and next among individual
      elementary modes (EM) in each lumped pathway. Both splits are described by the
      cybernetic control laws using operational and structural return-on-investments,
      respectively. That is, the distribution of uptake flux at the first split is
      dynamically regulated according to environmental conditions, while the subsequent
      split is based purely on the stoichiometry of EMs. The resulting model is
      conveniently represented in terms of lumped pathways which are fully identified
      with respect to yield coefficients of all products unlike classical LCMs based on
      instinctive lumping. These characteristics enable the model to account for the
      complete set of EMs for arbitrarily large metabolic networks despite containing
      only a small number of parameters which can be identified using minimal data.
      However, the inherent conflict of questing for quantification of larger networks
      with smaller number of parameters cannot be resolved without a mechanism for
      parameter tuning of an empirical nature. In this work, this is accomplished by
      manipulating the relative importance of EMs by tuning the cybernetic control of
      mode-averaged enzyme activity with an empirical parameter. In a case study
      involving aerobic batch growth of Saccharomyces cerevisiae, L-HCM is compared
      with LCM. The former provides a much more satisfactory prediction than the latter
      when parameters are identified from a few primary metabolites. On the other hand,
      the classical model is more accurate than L-HCM when sufficient datasets are
      involved in parameter identification. In applying the two models to a chemostat
      scenario, L-HCM shows a reasonable prediction on metabolic shift from respiration
      to fermentation due to the Crabtree effect, which LCM predicts unsatisfactorily.
      While L-HCM appears amenable to expeditious estimates of metabolic function with
      minimal data, the more detailed dynamic models [such as HCM or those of Young et
      al. (Young et al., Biotechnol Bioeng, 2008; 100: 542-559)] are best suited for
      accurate treatment of metabolism when the potential of modern omic technology is
      fully realized. However, in view of the monumental effort surrounding the
      development of detailed models from extensive omic measurements, the preliminary
      insight into the behavior of a genotype and metabolic engineering directives that
      can come from L-HCM is indeed valuable.

PMID- 20148412
TI  - Evolutionary optimization of peptide substrates for proteases that exhibit rapid
      hydrolysis kinetics.
AB  - Protease cleavage site recognition motifs can be identified using protease
      substrate discovery methodologies, but typically exhibit non-optimal specificity
      and activity. To enable evolutionary optimization of substrate cleavage kinetics,
      a two-color cellular library of peptide substrates (CLiPS) methodology was
      developed. Two-color CLiPS was applied to identify peptide substrates for the
      tobacco etch virus (TEV) protease from a random pentapeptide library, which were
      then optimized by screening of a focused, extended substrate library.
      Quantitative library screening yielded seven amino acid substrates exhibiting
      rapid hydrolysis by TEV protease and high sequence similarity to the native seven
      amino-acid substrate, with a strong consensus of EXLYPhiQG. Comparison of
      hydrolysis rates for a family of closely related substrates indicates that the
      native seven-residue TEV substrate co-evolved with TEV protease to facilitate
      highly efficient hydrolysis. Consensus motifs revealed by screening enabled
      database identification of a family of related, putative viral protease
      substrates. More generally, our results suggest that substrate evolution using
      CLiPS may be useful for optimizing substrate selectivity and activity to enable
      the design of more effective protease activity probes, molecular imaging agents,
      and prodrugs.

PMID- 20148413
TI  - Intraparticle concentration gradients for substrate and acidic product in
      immobilized cephalosporin C amidase and their dependencies on carrier
      characteristics and reaction parameters.
AB  - Cephalosporin C amidase was covalently attached using a protein loading of 7.0
      200 mg protein/g dry carrier on four epoxy-activated Sepabeads differing in
      particle size and pore diameter. Initial-rate kinetic analysis showed that for
      Sepabeads with small pore diameters (30-40 nm), the apparent K(M) of the amidase
      for hydrolysis of cephalosporin C at 37 degrees C and pH 8.0 increased
      approximately 3-fold in response to increased particle size (approximately 120
      400 microm) and increased amount of immobilized enzyme (7.0-70 mg protein/g dry
      carrier) while maximum specific activity (3.2 U/mg protein; 25% of free amidase)
      was affected only by particle size. In contrast, for Sepabeads with wide pores
      (150-250 nm), the K(M) was independent of the enzyme loading. Internal
      effectiveness factors calculated from observable Thiele modulus reflected the
      dependence of K(M) on geometrical parameters of the particles. A new method for
      determination of the overall intraparticle pH was developed based on luminescence
      lifetime measurements in the frequency domain. Sepabeads were doubly labeled
      using a lipophilic variant of the pH-sensitive dye fluorescein, and Ru(II)
      tris(4,7-diphenyl-1,10-phenantroline) whose phosphorescence properties are
      independent of pH. Luminescent lifetime measurements of doubly labeled particle
      suspensions showed superior signal-to-noise ratio compared to fluorescence
      intensity-based measurements using singly labeled particles. The difference at
      apparent steady state (DeltapH) between bulk (external pH) and intraparticle pH
      (internal pH) was as large as approximately 0.6 units. The DeltapH was dependent
      on substrate concentration, particle size, and pore diameter. Therefore, these
      results characterize the role of carrier characteristics and reaction parameters
      in the formation of concentration gradients for substrate and acidic product
      during hydrolysis of cephalosporin C by immobilized amidase. The strong pH
      dependence of the immobilized amidase underscores the importance of considering
      intraparticle pH gradients in the design of an efficient carrier-bound
      biocatalyst.

PMID- 20148414
TI  - Broad-host-range vectors for protein expression across gram negative hosts.
AB  - Expression of recombinant proteins across a range of different host organisms is
      often necessary in metabolic engineering applications. Doing so can be
      facilitated by the use of vectors having origins of replication with a broad-host
      range, the option for antibiotic resistance cassettes that are compatible with a
      particular host, in addition to sequences allowing for the effective
      transcription and translation of target proteins. We have created a modular set
      of broad-host-range expression vectors for protein expression in Gram negative
      bacteria. These vectors use the broad-host-range pBBR1 replicon as well as the
      arabinose-inducible P(BAD) promoter and are available with six different
      antibiotic resistance cassettes. We have demonstrated the use of these vectors in
      Escherichia coli, Pseudomonas putida, and Burkholderia cepacia.

PMID- 20148415
TI  - beta-Cyclodextrin hydrogels containing naphthaleneacetic acid for pH-sensitive
      release.
AB  - beta-Cyclodextrin (beta-CD) hydrogel was prepared in a strong alkali condition
      using epichlorohydrin (EPI) as a cross-linker, where the molar ratios of EPI to
      beta-CD were 8:1, 10:1, and 15:1. In order to endow a pH sensitivity to the
      hydrogel, naphthaleneacetic acid (NAA) was loaded in the hydrogel by taking
      advantage of its hydrophobic interaction with the cavities of beta-CD. The
      releases of blue dextran (a water-soluble dye) from the hydrogels were promoted,
      as the pHs of the media increased. When the molar ratio of EPI to beta-CD was
      lower, the degrees of release were higher, and the pH dependency of the release
      became more prominent. In fact, the swelling ratio of the hydrogels having a
      lower molar ratio of EPI to beta-CD was higher. The higher swelling ratio would
      account for the higher degree of release and the marked pH sensitivity.

PMID- 20148416
TI  - Modulation of alignment and differentiation of skeletal myoblasts by submicron
      ridges/grooves surface structure.
AB  - Alignment and fusion of myoblasts into parallel arrays of multinucleated myotubes
      are critical in skeletal muscle tissue engineering. It is well known that contact
      guidance by grooves/ridges structures induces myoblasts to align and to migrate
      along the anisotropic direction. In this study, two series of grooved substrata
      with different widths (450 and 900 nm) and different depths (100, 350, and 550
      nm) were studied on their effects on myoblast adhesion, proliferation, and
      differentiation into myotubes. We found that C2C12 cells were aligned and
      elongated along the direction of grooves. Groove depth was more influential on
      cellular morphology, proliferation, and differentiation than groove width. While
      cell proliferation was retarded on the grooved surfaces especially on the
      substrate with 900/550 nm (width/depth), differentiation was also enhanced on the
      patterned surfaces compared to the flat control. Our results demonstrated the
      potential of grooved substrata with submicron scale in skeletal muscle tissue
      engineering.

PMID- 20148417
TI  - Development of capillary array DNA sequencers for genome analysis.
AB  - Massive analysis of biological molecules is being successfully applied to
      elucidate various biological phenomena using techniques of molecular science.
      This new era was initiated by the Human Genome Project, which was supported by
      the development of various automated tools including DNA sequencers and DNA
      chips. A small project led by Akiyoshi Wada in Japan triggered the development of
      automated DNA analysis instruments. As one of the members of the project, the
      author has been engaged in developing DNA analyzers including capillary array DNA
      sequencers. Here, the principles and development of the main technologies related
      to capillary array DNA sequencers, which contributed to the completion of the
      Human Genome Project, are reviewed.

PMID- 20148419
TI  - PALM imaging and cluster analysis of protein heterogeneity at the cell surface.
AB  - The authors employed photoactivatable localization microscopy (PALM) and direct
      stochastic optical reconstruction microscopy (dSTORM) imaging and image analysis
      based on Ripley's K-function to quantify the distribution and heterogeneity of
      proteins at the cell plasma membrane. The membrane targeting sequence of the N
      terminal region of the T cell receptor-pathway kinase Lck fused to the photo
      convertible fluorescent protein tdEos (Lck(N10)-tdEos), clusters into sub-100 nm
      regions which cover approximately 7% of the cell surface. 2-channel PALM imaging
      of Lck(N10)-tdEos and the N-terminus of the kinase Src (Src(N15)-PS-CFP2) are
      demonstrated. Finally, T cell microclusters at the immune synapse are imaged at
      super-resolution using dSTORM, showing that conventional TIRF images contain
      unresolved, small clusters. These methods are generally applicable to other cell
      and fluorophore systems to quantify 2-D molecular clustering at nanometer scales.

PMID- 20148420
TI  - Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting
      multiple sclerosis patients.
AB  - MicroRNA (miRNA) are a class of post-transcriptional regulators of gene
      expression targeting mRNA for translational repression and/or degradation. We
      analyzed the expression of 365 miRNA in lymphocytes in relapsing-remitting MS
      patients, and show the first evidence for distinct miRNA expression profiles in
      CD4(+), CD8(+) and B cells in MS when compared with those in healthy volunteers.
      MiR-17-5p, which is involved in autoimmunity, was up-regulated in CD4(+) cells
      from MS patients. This was correlated with alterations in the expression of
      potential target genes of miR-17-5p, i.e. phosphatase and tensin homology and
      phosphatidyl-inositol-3-kinase regulatory subunit 1, which were down-regulated
      upon stimulation of CD4(+) cells with anti-CD3/CD28 in vitro. Functional
      experiments with a synthetic inhibitor of miR-17 supported the link between miRNA
      expression and the altered target gene expression. Moreover, we found distinct
      responses of deregulated miRNA to stimulation, i.e. miR-17-5p and miR-193a were
      strongly up-regulated, in contrast to the down-regulation of miR-497, miR-1 and
      miR-126. Other deregulated miRNA did not respond to the stimulation probably due
      to other, non-T-cell activation related, mechanisms in their mode of action. Our
      findings support the role of miRNA-dependent regulatory mechanisms in the
      immunopathogenesis of MS.

PMID- 20148421
TI  - Fcgamma receptor-mediated antigen uptake by lung DC contributes to allergic
      airway hyper-responsiveness and inflammation.
AB  - During asthma, lung DC capture and process antigens to initiate and maintain
      allergic Th2 cell responses to inhaled allergens. The aim of the study was to
      investigate whether allergen-specific IgG, generated during sensitization, can
      potentiate the acute airway inflammation through Fcgamma receptor (FcgammaR)
      mediated antigen uptake and enhance antigen presentation resulting in augmented T
      cell proliferation. We examined the impact of antigen presentation and T-cell
      stimulation on allergic airway hyperresponsiveness and inflammation using
      transgenic and gene-deficient mice. Both airway inflammation and eosinophilia in
      bronchoalveolar lavage fluid were markedly reduced in sensitized and challenged
      FcgammaR-deficient mice. Lung DC of WT, but not FcgammaR-deficient mice, induced
      increased antigen-specific CD4+ T-cell proliferation when pulsed with anti-OVA
      IgG immune complexes. Intranasal application of anti-OVA IgG immune complexes
      resulted in enhanced airway inflammation, eosinophilia and Th2 cytokine release,
      mediated through enhanced antigen-specific T-cell proliferation in vivo. Finally,
      antigen-specific IgG in the serum of sensitized mice led to a significant
      increase of antigen-specific CD4+ T-cell proliferation induced by WT, but not
      FcgammaR-deficient, lung DC. We conclude that FcgammaR-mediated enhanced antigen
      presentation and T-cell stimulation by lung DC has a significant impact on
      inflammatory responses following allergen challenge in asthma.

PMID- 20148422
TI  - Role of Treg in immune regulation of allergic diseases.
AB  - Allergy is a Th2-mediated disease that involves the formation of specific IgE
      antibodies against innocuous environmental substances. The prevalence of allergic
      diseases has dramatically increased over the past decades, affecting up to 30% of
      the population in industrialized countries. The understanding of mechanisms
      underlying allergic diseases as well as those operating in non-allergic healthy
      responses and allergen-specific immunotherapy has experienced exciting advances
      over the past 15 years. Studies in healthy non-atopic individuals and several
      clinical trials of allergen-specific immunotherapy have demonstrated that the
      induction of a tolerant state in peripheral T cells represent a key step in
      healthy immune responses to allergens. Both naturally occurring thymus-derived
      CD4+CD25+FOXP3+ Treg and inducible type 1 Treg inhibit the development of allergy
      via several mechanisms, including suppression of other effector Th1, Th2, Th17
      cells; suppression of eosinophils, mast cells and basophils; Ab isotype change
      from IgE to IgG4; suppression of inflammatory DC; and suppression of inflammatory
      cell migration to tissues. The identification of the molecules involved in these
      processes will contribute to the development of more efficient and safer
      treatment modalities.

PMID- 20148423
TI  - Blockade of GITR-GITRL interaction maintains Treg function to prolong allograft
      survival.
AB  - Involvement of Treg in transplant tolerance has been demonstrated in multiple
      models. During the active process of graft rejection, these regulatory cells are
      themselves regulated and inactivated, a process termed counter-regulation. We
      hypothesize that ligation of the costimulatory molecule glucocorticoid-induced
      TNF receptor-related protein (GITR) on Treg inhibits their ability to promote
      graft survival, and by blocking GITR ligation graft survival can be prolonged. To
      this aim, we have designed a soluble GITR fusion protein (GITR-Fc), which binds
      GITR ligand and inhibits activation of GITR. Here, we show that GITR-Fc prolonged
      mouse skin graft survival, and this prolongation is dependent on Treg. In a full
      MHC-mismatched skin graft setting, GITR-Fc significantly improved graft survival
      when used in combination with MR1, anti-CD40L, while GITR-Fc alone did not
      demonstrate graft prolongation. These results demonstrate that disruption of
      binding of GITR with GITR ligand may be an important strategy in prolonging
      allograft survival.

PMID- 20148424
TI  - An efficient protocol for NMR-spectroscopy-based structure determination of
      protein complexes in solution.

PMID- 20148425
TI  - Strongly binding cell-adhesive polypeptides of programmable valencies.

PMID- 20148426
TI  - Total synthesis of complestatin (chloropeptin II).

PMID- 20148427
TI  - Click-chemistry-derived tetracycline-amino acid conjugates exhibiting exceptional
      potency and exclusive recognition of the reverse tet repressor.
AB  - A click-chemistry-based synthesis of biologically active doxycycline-amino acid
      conjugates is described. Starting from 9-aminodoxycycline derivatives and
      complementary functionalized amino acids, ligation was accomplished by copper(I)
      catalyzed azide-alkyne [3+2] cycloaddition (CuAAC). The final products were
      tested in a variety of TetR and revTetR systems, and the C-terminally linked
      phenylalanine conjugate 12 c exhibited high selectivity for revTetR over TetR.
      Besides the unique property of the specific effector 12 c to effectively
      differentiate TetR and its reverse phenotype, the test compound proved to be
      almost devoid of any antibacterial activity; this will be highly beneficial for
      future applications to control gene expression in bacterial systems.

PMID- 20148429
TI  - Size-tunable highly luminescent SiO2 particles impregnated with number-adjusted
      CdTe nanocrystals.
AB  - Highly luminescent SiO(2) particles impregnated with CdTe nanocrystals (NCs) are
      prepared by a sol-gel procedure. Partial ligand exchange from thioglycolic acid
      to 3-mercaptopropyltrimethoxysilane (MPS) on the NCs enables retention of the
      initial photoluminescence (PL) efficiency of the NCs in water, while the
      simultaneous addition of a poor solvent (ethanol) results in regulated assembly
      of the NCs through condensation of hydrolyzed MPS. The SiO(2) particles thus
      prepared have, for example, a diameter of 16 nm and contain three NCs each. The
      PL efficiency of these particles is 40 %, while the initial efficiency is 46 % in
      a colloidal solution. The redshift and narrowed spectral width in PL observed
      after impregnation indicate that the concentration of NCs in these nearly reaches
      the ultimate value (on the order of 10(21) particles per liter). The porosity of
      these particles is investigated by means of N(2) adsorption-desorption isotherms.
      Due to the SiO(2) shell, these particles have higher stability in phosphate
      buffered saline buffer solution than the initial NCs. Their potential use for
      labeling in bio-applications is investigated by conjugating biotinylated
      immunoglobulin G to them by using streptavidin maleimide as linker. Successful
      conjugation is confirmed by electrophoresis in agarose gel. This preparation
      method is an important step towards fabricating intensely emitting biocompatible
      SiO(2) particles impregnated with semiconductor NCs.

PMID- 20148428
TI  - Redesigning the active site of transaldolase TalB from Escherichia coli: new
      variants with improved affinity towards nonphosphorylated substrates.
AB  - Recently, we reported on a transaldolase B variant (TalB F178Y) that is able to
      use dihydroxyacetone (DHA) as donor in aldol reactions. In a second round of
      protein engineering, we aimed at improving the affinity of this variant towards
      nonphosphorylated acceptor aldehydes, that is, glyceraldehyde (GA). The anion
      binding site was identified in the X-ray structure of TalB F178Y where a sulfate
      ion from the buffer was bound in the active site. Therefore, we performed site
      directed saturation mutagenesis at three residues forming the putative phosphate
      binding site, Arg181, Ser226 and Arg228. The focused libraries were screened for
      the formation of D-fructose from DHA and d,l-GA by using an adjusted colour
      assay. The best results with respect to the synthesis of D-fructose were achieved
      with the TalB F178Y/R181E variant, which exhibited an at least fivefold increase
      in affinity towards d,l-GA (K(M)=24 mM). We demonstrated that this double mutant
      can use D-GA, glycolaldehyde and the L-isomer, L-GA, as acceptor substrates. This
      resulted in preparative synthesis of D-fructose, D-xylulose and L-sorbose when
      DHA was used as donor. Hence, we engineered a DHA-dependent aldolase that can
      synthesise the formation of polyhydroxylated compounds from simple and cheap
      substrates at preparative scale.

PMID- 20148430
TI  - Electron microscopy and spectroscopy on the ultrafast timescale.

PMID- 20148431
TI  - Rare-earth oxide nanostructures: rules of rare-earth nitrate thermolysis in
      octadecylamine.
AB  - The decomposed regularity of rare-earth nitrates in octadecylamine (ODA) is
      discussed. The experimental results show that these nitrates can be divided into
      four types. For rare-earth nitrates with larger RE(3+) ions (RE=rare earth, La,
      Pr, Nd, Sm, Eu, Gd), the decomposed products exhibited platelike nanostructures.
      For those with smaller RE(3+) ions (RE=Y, Dy, Ho, Er, Tm, Yb), the decomposed
      products exhibited beltlike nanostructures. For terbium nitrate with a middle
      RE(3+) ion, the decomposed product exhibited a rodlike nanostructure. The
      corresponding rare-earth oxides, with the same morphologies as their precursors,
      could be obtained when these decomposed products were calcined. For cerium
      nitrate, which showed the greatest differences, flowerlike cerium oxide could be
      obtained directly from decomposition of the nitrate without further calcination.
      This regularity is explained on the basis of the lanthanide contraction. Owing to
      their differences in electron configuration, ionic radius, and crystal structure,
      such a nitrate family therefore shows different thermolysis properties. In
      addition, the potential application of these as-obtained rare-earth oxides as
      catalysts and luminescent materials was investigated. The advantages of this
      method for rare-earth oxides includes simplicity, high yield, low cost, and ease
      of scale-up, which are of great importance for their industrial applications.

PMID- 20148434
TI  - Development of nitrergic neurons in the nervous system of the locust embryo.
AB  - We followed the development of the nitric oxide-cyclic guanosine monophosphate
      (NO-cGMP) system during locust embryogenesis in whole mount nervous systems and
      brain sections by using various cytochemical techniques. We visualized NO
      sensitive neurons by cGMP immunofluorescence after incubation with an NO donor in
      the presence of the soluble guanylyl cyclase (sGC) activator YC-1 and the
      phosphodiesterase-inhibitor isobutyl-methyl-xanthine (IBMX). Central nervous
      system (CNS) cells respond to NO as early as 38% embryogenesis. By using the
      NADPH-diaphorase technique, we identified somata and neurites of possible NO
      synthesizing cells in the CNS. The first NADPH-diaphorase-positive cell bodies
      appear around 40% embryogenesis in the brain and at 47% in the ventral nerve
      cord. The number of positive cells reaches the full complement of adult cells at
      80%. In the brain, some structures, e.g., the mushroom bodies acquire NADPH
      diaphorase staining only postembryonically. Immunolocalization of L-citrulline
      confirmed the presence of NOS in NADPH-diaphorase-stained neurons and, in
      addition, indicated enzymatic activity in vivo. In whole mount ventral nerve
      cords, citrulline immunolabeling was present in varying subsets of NADPH
      diaphorase-positive cells, but staining was very variable and often weak.
      However, in a regeneration paradigm in which one of the two connectives between
      ganglia had been crushed, strong, reliable staining was observed as early as 60%
      embryogenesis. Thus, citrulline immunolabeling appears to reflect specific
      activity of NOS. However, in younger embryos, NOS may not always be
      constitutively active or may be so at a very low level, below the citrulline
      antibody detection threshold. For the CNS, histochemical markers for NOS do not
      provide conclusive evidence for a developmental role of this enzyme.

PMID- 20148438
TI  - Comparative analyses of the neuron numbers and volumes of the amygdaloid complex
      in old and new world primates.
AB  - The amygdaloid complex (AC), a key component of the limbic system, is a brain
      region critical for the detection and interpretation of emotionally salient
      information. Therefore, changes in its structure and function are likely to
      provide correlates of mood and emotion disorders, diseases that afflict a large
      portion of the human population. Previous gross comparisons of the AC in control
      and diseased individuals have, however, mainly failed to discover these expected
      correlations with diseases. We have characterized AC nuclei in different nonhuman
      primate species to establish a baseline for more refined comparisons between the
      normal and the diseased amygdala. AC nuclei volume and neuron number in 19
      subdivisions are reported from 13 Old and New World primate brains, spanning five
      primate species, and compared with corresponding data from humans. Analysis of
      the four largest AC nuclei revealed that volume and neuron number of one
      component, the central nucleus, has a negative allometric relationship with total
      amygdala volume and neuron number, which is in contrast with the isometric
      relationship found in the other AC nuclei (for both neuron number and volume).
      Neuron density decreases across all four nuclei according to a single power law
      with an exponent of about minus one-half. Because we have included quantitative
      comparisons with great apes and humans, our conclusions apply to human brains,
      and our scaling laws can potentially be used to study the anatomical correlates
      of the amygdala in disorders involving pathological emotion processing.

PMID- 20148439
TI  - Three subdivisions of the auditory midbrain in chicks (Gallus gallus) identified
      by their afferent and commissural projections.
AB  - The auditory midbrain is a site of convergence of multiple auditory channels from
      the brainstem. In birds, two separate ascending channels have been identified,
      through which time and intensity information is sent to the nucleus
      mesencephalicus lateralis, pars dorsalis (MLd), the homologue of the central
      nucleus of the mammalian inferior colliculus. Using in vivo anterograde and
      retrograde tracing techniques, the current study provides two lines of anatomical
      evidence supporting the presence of a third ascending channel to the chick MLd.
      First, three non-overlapping zones of the MLd receive inputs from three distinct
      cell groups in the caudodorsal brainstem. The projections from the nucleus
      angularis (NA) and nucleus laminaris (NL) are predominantly contralateral and may
      correspond to the time and intensity channels. A rostromedial portion of the MLd
      receives bilateral projections mainly from the regio intermedius, an interposed
      region of cells lying at a caudal level between the NL and NA, as well as
      scattered neurons embedded in the 8th nerve tract, and probably a very ventral
      region of the NA. Second, the bilateral zones of the MLd on two sides of the
      brain are reciprocally connected and do not interact with other zones of the MLd
      via commissural connections. In contrast, the NL-recipient zone projects
      contralaterally upon the NA-recipient zone. The structural separation of the
      third pathway from the NA and NL projections suggests a third information
      processing channel, in parallel with the time and intensity channels. Neurons in
      the third channel appear to process very low frequency information including
      infrasound, probably utilizing different mechanisms than that underlying higher
      frequency processing.

PMID- 20148441
TI  - Common-sense beliefs about cancer and health practices among women completing
      treatment for breast cancer.
AB  - OBJECTIVE: Following the end of adjuvant treatment, breast cancer survivors must
      cope with uncertainty related to the possibility of recurrence and the loss of
      the 'safety net' treatment provides. This study examined breast cancer survivors'
      efforts to manage uncertainty by making lifestyle changes, such as improvement in
      diet and exercise. We further investigated the role of women's common-sense
      beliefs about their cancer, as described by Leventhal's self-regulation theory,
      in explaining post-treatment changes. METHOD: At 3 weeks and 3 months post
      treatment, 79 women who received adjuvant chemotherapy and/or radiation therapy
      for stages 0-III breast cancer (mean age=55 years) completed assessments of
      changes in health practices and other behaviors. Participants also completed
      measures of beliefs about the causes, course, personal control, and consequences
      of their cancer. RESULTS: Survivors reported behavior changes directed toward
      improving physical, emotional, and spiritual well-being. Results further
      indicated that women who believed their cancer had more severe consequences and
      those who attributed the development of cancer or the prevention of recurrence to
      health behaviors or stress were most likely to report improvement in diet or
      physical activity and reduction in alcohol use or stress. CONCLUSIONS: Findings
      suggest that breast cancer survivors are poised to make lifestyle changes after
      treatment ends, creating an opportune time for health promotion interventions.
      Understanding women's cancer beliefs could help guide the development of
      tailored, proactive interventions to improve the health and well-being of breast
      cancer survivors.

PMID- 20148442
TI  - Assessment of psychological distress in cancer patients: a pivotal role for
      clinical interview.
AB  - OBJECTIVE: The evaluation of psychological distress in cancer patients recently
      entered oncologic clinical practice. The objective of this study was to evaluate
      the role of clinical interview within psycho-oncologic assessment. METHODS:
      Questionnaires assessing distress (PDI), psychopathology (MHQ, HADS) and needs
      (NEQ) and a subsequent clinical interview were proposed to 320 consecutive
      inpatients from the Oncology Department of Careggi Hospital in Florence. RESULTS:
      The clinical interview made it possible to evaluate a significant percentage of
      patients (30%) who did not fill in questionnaires and to detect the presence of
      distress in 39 (13.7%) patients who would not have received a diagnosis in a
      protocol for the assessment of distress based only on questionnaires. It also
      provided the possibility to ask for help or to receive clinical support to a high
      percentage of patients (44.1%) who had not requested to speak to a psychologist
      through the questionnaires (NEQ). Moreover, 25% of patients who received
      prolonged clinical support had a low score in tests detecting distress,
      indicating that the opportunity for therapeutic support can emerge during a
      clinical interview, also in the absence of relevant symptoms detected by
      questionnaires. CONCLUSIONS: The use of more than one questionnaire in the
      assessment of distress and psychopathology is associated with reduced compliance
      and redundant information. On the other hand, clinical interview has a pivotal
      role in clinical evaluation and access to psychological support. We conclude that
      optimal efficacy of programs assessing distress in cancer patients is reached
      when a single questionnaire evaluating distress is associated with a clinical
      interview.

PMID- 20148440
TI  - Morphology of dopaminergic amacrine cells in the mouse retina: independence from
      homotypic interactions.
AB  - To determine the role of homotypic interactions between neighboring dopaminergic
      amacrine (DA) cells upon dendritic morphogenesis, the morphology of single cells
      was examined relative to the positioning of all neighboring homotypic cells. For
      each labeled cell, the dendritic field was reconstructed, its Voronoi domain was
      calculated, and the two were related. The dendritic fields of DA cells were
      observed to be large, sparse, and highly irregular. Dendrites readily overlapped
      those of neighboring cells, showing no evidence for dendritic tiling or inter
      digitation consistent with homotypic repulsion or avoidance. Furthermore, a
      direct comparison of dendritic field area with the Voronoi domain area of the
      same cell showed no evidence for dendritic growth being constrained or biased by
      the local distribution of homotypic neighbors in wild-type retinas. A comparison
      of the processes of adjacent filled cells confirmed their immediate proximity to
      one another within the inner plexiform layer, indicating that they do not engage
      in mutual avoidance by coursing at different depths. Together, these results
      suggest that the morphogenesis of DA cells is independent of homotypic
      interactions. However, in the absence of the pro-apoptotic Bax gene, which yields
      a fourfold increase in DA cell number, a small but significant reduction in
      dendritic field size was obtained, although not so great as would be predicted by
      the increase in density. The present results are considered in light of recent
      studies on the role of cell adhesion molecules expressed by developing DA cells.

PMID- 20148443
TI  - Transplantation strategies for the management of patients with myelodysplastic
      syndromes.
AB  - Allogeneic stem cell transplantation (SCT) is the only therapeutic modality at
      present that may be delivered with curative intent in patients with
      myelodysplastic syndromes (MDS). Allogeneic CST replaces recipient dysplastic
      hemopoiesis with healthy donor haemopoiesis and immune system with an attendant
      graft-versus-leukemia (GvL) effect. Its applicability, however, is limited by the
      age of MDS patients, high rates of transplant-related mortality (TRM) and
      availability of a suitable HLA-matched donor. Results from several large centres
      indicated 3-year overall survival (OS) rates of 20-45%, which are almost equal
      with the results obtained by intensive chemotherapy alone. Failure was due
      primarily to TRM in patients with low-risk MDS and to disease recurrence in
      patients with high-risk MDS. Allogeneic SCT from matched unrelated donors produce
      poorer results than matched related siblings' transplantations. In an attempt to
      reduce TRM and deliver allogeneic SCT in a greater subgroup of MDS patients, many
      researchers used reduced-intensity allografts (RIC or "mini"-allograft) for MDS.
      Although differences in patient populations, preparative regimens, and graft
      versus-host disease (GvHD) prophylaxis, as well as donor source (related vs.
      unrelated) have to be considered, OS of up to 40% at 3 years and disease-free
      survival (DFS) rates of almost 35% at 3 years have been reported in selected
      centres. However, randomized prospective studies are needed to further address
      the optimal choice of transplant conditioning intensity in MDS. Autologous SCT
      has been extremely investigated in MDS. It is limited to patients who have
      achieved a complete remission (CR), can be harvested, and are candidates for the
      procedure. Autologous SCT after successful induction chemotherapy may increase
      the proportion of long-term survivors, thus improving CR duration in some
      patients with MDS, particularly in younger patients in remission. Results for
      older patients are unsatisfactory. The relapse rate is up to 75%, with a 2-year
      probability of DFS of only 25% for patients 40-60 years of age. Therefore, there
      is very limited enthusiasm for the future of autologous SCT in the management of
      MDS patients.

PMID- 20148444
TI  - Molecular diagnosis and monitoring of chronic myelogenous leukemia: BCR-Abl and
      more.
AB  - The current treatment of chronic myelogenous leukemia (CML) is one of the most
      successful examples of molecularly targeted therapy in cancer. The identification
      of the fusion oncogene BCR-ABL allowed the discovery of small molecule inhibitors
      of its tyrosine kinase activity which, in turn, have literally revolutionized the
      treatment of this disease. However, large part of a successful clinical
      management of CML relies on appropriate diagnosis, molecular monitoring and
      identification of mutations potentially leading to drug resistance. These issues
      are discussed here together with an overview on how patients treated with
      tyrosine kinase inhibitors should be monitored.

PMID- 20148445
TI  - Overview of positron emission tomography chemistry: clinical and technical
      considerations and combination with computed tomography.
AB  - The concept of emission and transmission tomography was introduced by David Kuhl
      and Roy Edwards in the late 1950s. Their work later led to the design and
      construction of several tomographic instruments at the University of
      Pennsylvania. Tomographic imaging techniques were further developed by Michel Ter
      Pogossian, Michael E. Phelps and others at the Washington University School of
      Medicine. Positron emission tomography (PET) is a nuclear medicine imaging
      technique which produces a 3-dimensional image or map of functional processes in
      the body. The system detects pairs of gamma rays emitted indirectly by a positron
      emitting radionuclide (tracer), which is introduced into the body on a
      biologically active molecule. Images of tracer concentration in 3-dimensional
      space within the body are then reconstructed by computer analysis. In modern
      scanners, this reconstruction is often accomplished with the aid of a CT X-ray
      scan performed on the patient during the same session, in the same machine. If
      the biologically active molecule chosen for PET is 18F-fluorodeoxyglucose (FDG),
      an analogue of glucose, the concentrations of tracer imaged give tissue metabolic
      activity in terms of regional glucose uptake. Although use of this tracer results
      in the most common type of PET scan, other tracer molecules are used in PET to
      image the tissue concentration of many other types of molecules of interest. The
      main role of this article was to analyse the available types of
      radiopharmaceuticals used in PET-CT along with the principles of its clinical and
      technical considerations.

PMID- 20148446
TI  - Surgical approaches towards fertility preservation in young patients with early
      invasive cervical carcinoma.
AB  - Cervical cancer still remains one of the major problems in developing countries.
      The last decade of 20th century has seen a trend towards more conservative
      surgical approaches in the treatment of early-stage disease in young patients.
      The trend of delaying childbearing, nowadays, increases preservation of
      fertility, and reproductive function is a major concern when counseling these
      young women with regard to the effects of treatment for cervical cancer. Radical
      trachelectomy, either with abdominal or vaginal surgical approach, showed promise
      as treatment option in young patients with early cervical cancer. The basic
      principle of such a surgical approach is an operation aiming at preserving the
      uterine body and removing the cervix, parametrium, with bilateral pelvic
      lymphadenectomy, and creating a utero-vaginal anastomosis, either
      laparoscopically or by laparotomy. Both surgical approaches are evaluated after a
      search of the relevant literature in Pub Med or Medline.

PMID- 20148447
TI  - Modern treatment of invasive carcinoma of the uterine cervix.
AB  - Treatment of invasive cervical carcinoma is determined by the clinical disease
      stage. Microinvasive carcinoma of the uterine cervix, due to its limited
      metastatic potential, is usually curable with non-radical treatment. There are no
      standard approaches to the treatment of stage Ib-IIa carcinoma of the uterine
      cervix. Both radical surgery and radical radiotherapy are utilized with similar
      efficacy but with different associated morbidity and complications. Stage Ib1 was
      commonly treated with radical hysterectomy plus pelvic lymphadenectomy.
      Laparoscopically-assisted radical vaginal hysterectomy demonstrated similar
      efficacy and recurrence rates for this disease stage. In cases where fertility is
      to be preserved, radical vaginal trachelectomy is a valid option for small
      cervical cancers. Among the papers dealing with bulky cervical disease (stages Ib
      IIa) a great deal of disagreement is evident. Some oncologic centres prefer
      primary surgery with postoperative radiotherapy, with or without chemotherapy,
      while others prefer primary chemoradiotherapy. Moreover, as a possible
      alternative, neoadjuvant chemotherapy followed by radical surgery is recommended
      for stage Ib2 disease. Simultaneous chemoradiation is being introduced as a new
      standard for advanced cancer, since it has been clearly demonstrated that it can
      prolong disease-free and overall survival. The treatment of recurrent carcinoma
      depends on the type of previous treatment, site and extent of recurrent disease,
      and on the disease-free period and general health of the patient. In conclusion,
      the decision on the treatment approach for invasive carcinoma of the uterine
      cervix should be individualized, based on numerous factors, such as disease
      stage, general health of the patient, cancer-related factors, in order to choose
      the best approach with minimal complications.

PMID- 20148448
TI  - Surgery for patients with gastric cancer in the terminal stage of the illness -
      TNM stage IV.
AB  - PURPOSE: To assess any survival advantage in patients with incurable gastric
      cancer who had undergone resection, bypass or exploratory surgery. In
      nonresectable patients with pain, the effect of celiac plexus neurolysis was
      assessed. METHODS: We retrospectively analysed data of 330 patients, operated
      between 1992 and 2006. The patients were followed until death or last
      examination. Incurable gastric cancer was defined as TNM stage IV disease:
      locally advanced (LA), with solitary distant metastasis (SM) or with multiple
      metastases and/or peritoneal carcinomatosis (MMC). The patients were divided into
      these 3 groups. Their postoperative survival was calculated and compared in
      relation to the surgical technique used. Factors which influenced mortality and
      survival were identified. RESULTS: 131 patients (39.7%) had locally LA cancer, 98
      (29.7%) SM, and 101 (30.6%) belonged to the MMC group. The surgical procedures
      included 138 (41.8%) exploratory laparotomies, 84 (25.5%) bypass procedures and
      108 (32.7%) resections. Thirty-three (10%) unresectable patients with pain
      underwent celiac plexus neurolysis. The mean survival was 21.8 months after
      resections, 7 months after by-passes and 4.8 after exploratory laparotomies (p =
      0.0001). It was 14.57 months (p=0.001) in the LA group, 12.53 (p = 0.005) in the
      SM group, and 5.2 in the MMC group. Survival was shorter in patients with
      preoperative weight loss of more than 20 kg (3.2 months, p <0.0001).
      Postoperative 30-day mortality was 23.2% after exploratory laparotomies, 23.8%
      after bypasses and 20.4% after resections. Increased mortality was observed in
      the MMC group (27.7%) and in multivisceral resections (41%, p > 0.05), while
      significantly increased mortality occurred in patients with weight loss of over
      20 kg (32%, p=0.03). Celiac plexus neurolysis was immediately effective in 30 out
      of 33 (91%) patients (p=0.0001), while 3 months later it was still effective in
      15 (45.5%) patients (p=0.08). CONCLUSION: Resections are suggested in the LA and
      SM groups, and neurolysis in all nonresected patients with pain.

PMID- 20148450
TI  - Long-term survival of patients with carcinoid tumor and liver metastases.
AB  - PURPOSE: To determine long-term survival and long-term stable disease in patients
      with atypical carcinoid tumor with liver metastases. METHODS: From 1993 till
      2008, the records of 56 patients with atypical carcinoid were reviewed. Nine of
      them who had liver metastases were analysed. All patients had carcinoid tumors
      confirmed histologically. Treatment, including chemotherapy and somatostatin, was
      given as palliative therapy of short duration. RESULTS: The median survival of 9
      patients was 50 months (range 12-156). Three of 9 (33.33%) patients died of
      disease, at 12, 48 and 50 months. The remaining 6 patients are alive after 36,
      40, 108, 120, 156 and 156 months, practically without treatment and experiencing
      a high quality of life. CONCLUSION: Six of 9 (66.66%) patients are alive having
      received almost no treatment for many years.

PMID- 20148449
TI  - Capecitabine and oxaliplatin (XELOX) as first-line treatment for patients with
      metastatic colorectal cancer.
AB  - PURPOSE: For almost 40 years, 5-fluorouracil (5-FU) had been the only drug with
      demonstrated activity against (CRC), commonly used in combination with leucovorin
      (LV). Oxaliplatin and capecitabine are two relatively novel drugs used in the
      treatment of CRC. These drugs have been found to act synergistically, both in
      vivo and in vitro and their combination (XELOX) is highly active in metastatic
      colorectal cancer (mCRC). The aim of this study was to determine the safety and
      efficacy of XELOX in patients with mCRC. METHODS: The study endpoints were
      response rates, toxicity, progression free (PFS) and overall survival (OS). XELOX
      was administered as first line treatment to patients with mCRC. Patient selection
      criteria included histological confirmation of mCRC, ECOG performance status (PS)
      <or=2, and adequate bone marrow, renal and hepatic function. Patients received
      oxaliplatin 130 mg/m(2) i.v., day 1, and oral capecitabine 1000 mg/m(2) twice
      daily, days 1-14, every 3 weeks. RESULTS: 34 patients were treated with XELOX;
      males/ females 23/11, median age 53.5 years (range 42-65), ECOG PS 0/1 52%/48%.
      Metastatic sites were the liver (23/34; 67%), lung (7/34; 20%), and bone (4/34;
      11%). No patient achieved complete response (CR), 14 patients showed partial
      response (PR), 8 stable disease (SD) and 11 progressed (PD). Median PFS was 5.5
      months, median OS 12.9 months and 1-year survival 52%. CONCLUSION: The
      combination of oral capecitabine with i.v. oxaliplatin appears to be effective
      and well tolerated in patients with mCRC.

PMID- 20148451
TI  - Whole abdominal irradiation in endometrial cancer - a single institution study.
AB  - PURPOSE: To examine the use of whole abdominal irradiation (WAI) open field
      technique in patients with stage III endometrial cancer (EC). METHODS: Between
      1993 and 2007, 26 patients (age 39-70 years, median 58) with stage III EC (IIIA
      15, IIIB 2, IIIC 8) were treated with WAI after primary surgery. Five (21))
      patients had grade 1 disease, 18 (67%) grade 2 and 3 (12%) grade 3. In 2 (8%)
      patients a second laparotomy was carried out before the radiotherapy (RT)
      referral. Ascites and positive peritoneal cytology was present in 3 (15%) and 4
      (20%) patients, respectively. After surgery, residua < 2 cm in the upper abdomen
      were left in 2 patients. WAI was delivered using Co 60 anterior-posterior photon
      fields to encompass the peritoneal cavity. In 84% of the patients WAI consisted
      of 30 Gy, delivered mainly in daily fractions of 1.5 Gy (81%), 5 fractions per
      week. For the remaining patients the dose was 25 Gy (8%) and 20 Gy (8%),
      respectively. After abdominal RT, 85% of the patients were given a pelvic boost
      to reach 45 - 50 Gy with 1.8 Gy/fraction/day, using a Co 60 unit. In 5 (19%)
      patients boost to 45-50 Gy with 1.8 Gy/fraction/day to other risk sites was also
      given. Two (8%) of 26 patients received 2 cycles of platinum-based chemotherapy.
      The mean follow-up time was 13.41 years. RESULTS: The treatment time ranged from
      14-74 days, median 48. The overall survival (OS) rate was 93% at 5, 10 and 14
      years. Ten (38.5%) patients received their treatment with no interruption, and in
      16 (61.5%) patients RT was transiently interrupted because of acute
      gastrointestinal and hematological toxicity. Neither grade 4 acute complications
      nor mortality while receiving treatment were observed. Late side effects (grade 2
      gastrointestinal complications) developed in 1 (5%) patient. During the
      observation period a second primary malignancy was recorded in 1 patient.
      CONCLUSION: WAI achieves a quite favorable 5- and 14-year survival rate with an
      acceptable risk of acute and late side effects in properly selected patients with
      stage III EC. WAI as a sole or a part of combined treatment warrants further
      investigation in patients with high-risk EC.

PMID- 20148452
TI  - Characteristics and prognosis of breast cancer in younger women.
AB  - PURPOSE: Women under 40 years of age comprise a small proportion of patients with
      breast cancer. Clinical and pathological features of the disease in these
      patients are different from those in older patients with this type of cancer. In
      the present study we investigated the clinicopathological characteristics and
      prognostic factors in young patients with breast cancer. METHODS: We
      retrospectively reviewed the medical records of 249 consecutive breast cancer
      patients who were admitted to our department between August 2001 and December
      2005. Clinicopathological features were determined both in patients under and
      over 40 years of age. RESULTS: 106 (42.5%) patients were under and 143 (57.5%)
      were over 40 years. The mean age was 35.2 years for those under 40 years and 54
      for those older than 40 years. At diagnosis, 10.4% of the patients in the younger
      age group and 7.0% in the older age group had metastasis (p=0.500). Patients in
      the younger age group exhibited higher estrogen receptor (ER) negativity (48.1
      vs. 37.1%) (p=0.425) and a higher percentage of family history of breast cancer
      (4.7 vs. 2.8%) (p=0.651). Breast cancer in younger women was more frequently
      associated with other poor prognostic factors such as perineural and/or
      lymphovascular invasion. The 5-year overall survival was 6.3% for the younger
      patients and 22.2% for the older ones (p=0.004). CONCLUSION: This study
      demonstrates that breast cancer in younger patients has significantly more poor
      prognostic features compared to older ones.

PMID- 20148453
TI  - The basic morphological characteristics of astrocytomas in Vojvodina in the
      period 2001-2006.
AB  - PURPOSE: Astrocytomas are the most common primary intracranial neoplasms. The aim
      of this investigation was to register the age, sex, tumor localization, frequency
      and histological types of patients with astrocytomas. METHODS: The investigation
      was carried out from January 2001 to June 2006 and included 490 consecutive
      patients of both sexes with diagnosed intracranial tumors, who had undergone
      surgical treatment at the Neurosurgery Clinic of the Clinical Centre of
      Vojvodina. Tumor histological studies were carried out in the Laboratory of the
      Centre for Pathology and Histology of the Clinical Centre of Vojvodina. Out of
      490 patients with diagnosed intracranial tumors, 139 (28.4%) had astrocytomas.
      RESULTS: Astrocytomas were more frequent in males (63.3%) and were most common in
      the 50-59-year age group (39.5%). The most common localization was the frontal
      region (30.2%), more commonly on the right side (51.8%). In regard to other
      histological types of intracranial tumors, astrocytomas were more frequent in
      males (34.8%). Grade III astrocytomas were most common (55.4%). The frequency of
      hemorrhage and thrombosis showed a positive correlation with the histological
      grade of astrocytomas. CONCLUSION: The typical patient with astrocytoma is a male
      of 50-59 years. The tumor is grade III located in the right frontal region.

PMID- 20148454
TI  - Impact of percent positive random biopsies on biochemical outcome in prostate
      cancer patients treated with external beam radiotherapy with or without androgen
      deprivation.
AB  - PURPOSE: To identify the prognostic factors for biochemical outcome in patients
      with localized prostatic adenocarcinoma treated with external beam radiotherapy
      (EBRT) with or without androgen deprivation (AD) and to investigate the impact of
      percent positive prostate core biopsies (PCB%). METHODS: From 1998 through 2003,
      333 patients with newly diagnosed localized prostate cancer were retrospectively
      analyzed. The patients were treated in two institutions with definitive EBRT to a
      median dose of 72 Gy and 80% of them received short- or long-term AD. Biochemical
      failure was defined using ASTRO criteria with 3 consecutive rises in prostate
      specific antigen (PSA). RESULTS: Median follow up was 36 months. Gleason score,
      initial PSA, risk grouping, PCB%, AD and total duration of AD were found to be
      significant predictors for biochemical outcome in univariate analysis.
      Independent predictors for PSA failure on multivariate analysis were PCB% and
      duration of AD. Among 3 risk groups, in the intermediate risk group the
      biochemical control was significantly better in patients with < 67% positive core
      biopsies. In the subgroup analysis of patients who received a prostatic dose <or=
      70.2 Gy, and patients with no hormonal or short-term hormonal manipulation the 5
      year biochemical outcome was significantly reduced in patients with >or= 67%
      positive core biopsies. These significant differences did not exist in patients
      receiving > 70.2 Gy and long-term hormonal therapy. CONCLUSION: Our results
      suggest that high PCB% could be a predictor of biochemical relapse, especially in
      the intermediate risk group. The role of PCB% in prostate cancer should be
      investigated in further trials.

PMID- 20148455
TI  - Expression of HER2/neu, estrogen and progesterone receptors, CA 125 and CA19-9 on
      cancer cell membrane in patients with serous and mucinous carcinoma of the ovary.
AB  - PURPOSE: To examine the expression of the membrane markers of estrogen (ER) and
      progesterone receptors (PR), CA-125, CA 19-9 and HER2/neu in ovarian cancer
      tissues. METHODS: Fifty-four samples of ovarian cancer tissues originating from
      55 patients were examined by immunohistochemistry. Forty-three had serous
      papillary ovarian cancer, 9 of which were grade I, 12 grade II and 2 grade III.
      Twelve patients had a classic mucinous ovarian cancer, 5 of which were grade I, 4
      grade II and 0 grade III. RESULTS: Out of 43 patients with serous ovarian cancer,
      7 expressed both steroid receptors, 22 had only one (10 ER and 12 PR), while 14
      were negative. Only 2/12 patients with classic mucinous ovarian cancer expressed
      of both receptors. CA-125 was expressed in 37/43 patients with serous ovarian
      cancer and in 4/12 patients with classic mucinous ovarian cancer. CA 19-9 was
      expressed in 3/43 patients with serous ovarian cancer, and coexpressed with CA
      125 in 2/3 patients. In patients with classic mucinous ovarian cancer, 4/12 had
      expression of CA 19-9 without coexpression with CA-125. HER2/neu positivity (3+)
      was proven in only one case with classic mucinous ovarian cancer, and any other
      expression (1+) in 7 additional patients (1 mucinous and 6 serous ovarian
      cancers). CONCLUSION: Positive HER2/neu expression in the cells of ovarian cancer
      is very rare and HER2/neu overexpression is even rarer. Expression of ER and PR
      does not depend on tumor grade and/or at least not in grade I and II. Positive CA
      19-9 expression may be present not only in cases of classic mucinous ovarian
      cancer but also in typical serous ovarian cancer. However, in the classic
      mucinous ovarian cancer, CA-125 may be expressed, though in relatively low
      percentage.

PMID- 20148456
TI  - Chromosomal aberrations after exposure to low doses of ionizing radiation.
AB  - PURPOSE: To compare the incidence of chromosomal aberrations (CA) in healthy
      medical workers occupationally exposed to ionizing radiation (IR) and in non
      exposed healthy population. METHODS: This was a 4-year study with 462 subjects,
      mean age 42.3 years, occupationally exposed to IR (exposed group - E), and 95
      subjects, mean age 35.2 years, not exposed to IR (control group - C), during the
      same time period and from the same territory. Thermoluminescence dosimeters (TLD)
      were used for assessment of IR exposure. Modified Moorhead's micro method for
      peripheral blood lymphocytes and conventional cytogenetic technique of CA was
      used for analysis of CA. The karyotype of 200 lymphocytes in metaphase was
      analysed by immersion light microscope. RESULTS: The average annual absorbed dose
      measured by TLD was 14.5 mSv in group E and 2.8 mSv in group C exposed to natural
      level of radioactivity. The incidence of CA was 21.6% in group E and 2.1% in
      group C (p <0.05), while non-specific chromosomal lesions (gaps, breaks,
      elongations) were equal in both groups (22%). In group E, the highest incidence
      was found in nuclear medicine workers (42.6%), then in orthopedic surgeons
      (27.08%). Highly significant difference (p <0.001) was found in the number of
      aberrant cells and the sum of CA between group E and C. The sum of CA and the
      number of aberrant cells were positively correlated with the duration of exposure
      (p < 0.001), and to a lesser degree with age (p < 0.05) in group E. In group C,
      this correlation was negative and insignificant. In group E, subjects with
      duration of occupational exposure (DOE) up to 15 years (subgroup E I=327) had
      significantly less number of aberrant cells and CA in comparison with the
      subjects with DOE over 15 years (subgroup E II=135) (p < 0.01). CONCLUSION: Long
      term occupational exposure to low doses IR contributes to the development and
      increased frequency of specific CA (like dicentrics), but varies in relation to
      different working places. The majority of subjects had no other genetic
      modifications (non-specific chromosomal lesions) affected by low doses of IR.

PMID- 20148457
TI  - Effects of vitamin C and N-acetylcysteine against cyclophosphamide-induced
      genotoxicity in exfoliated bladder cells of mice in vivo.
AB  - PURPOSE: To investigate the effects of vitamin C and N-acetylcysteine (NAC)
      against cyclophosphamide (CP) -induced genotoxic damage in exfoliated bladder
      cells of mice by micronucleus (MN) assay. METHODS: For each experimental step, 6
      8 Swiss albino balb/c male mice were used. CP was used as positive control.
      Vitamin C (10, 30 and 60 mg/kg) and CP (51.6 mg/kg) were administered
      intraperitoneally to the experimental animals. Vitamin C was administered twice,
      one dose 24 h prior to the CP administration and the second dose simultaneously
      with the CP. NAC (200, 400 and 800 mg/kg) was administered by gavage for 7
      consecutive days before the injection of CP. Distilled water and normal saline as
      negative controls I and II were used, respectively. Ten days after CP treatment,
      the mice were sacrificed and bladders were isolated and cut, and exfoliated cells
      were scraped from the bladder walls. Air-dried smears were stained by Feulgen
      reaction. MN frequencies were scored in 1000 epithelial cells per animal and
      defined as MN per thousand (per thousand). RESULTS: Three doses of vitamin C (10,
      30 and 60 mg/ kg) showed a significant inhibitory effect on MN frequencies in
      mouse bladder cells when compared with those of positive control group (p <0.05).
      Dose-dependent inhibitory effect of vitamin C was observed only between the doses
      of 10 and 60 mg/kg (p <0.05). Histopathological changes that depended on CP-
      induced inflammatory infiltration and haemorrhage in mucosa propria were not
      observed in all 3 vitamin C doses. Three doses of NAC (200, 400 and 800 mg/kg)
      inhibited the CP-induced genotoxicity (p <0.05), however, the antigenotoxic
      effect of NAC was not dose-dependent. Histopathological changes that depended on
      CP-induced inflammatory infiltration and haemorrhage in mucosa propria were not
      observed in 200 and 400 mg/kg NAC dosage. The extent of desquamation in bladder
      was similar in all 3 doses of NAC when compared with the positive control group.
      CONCLUSION: Our study indicated that vitamin C and NAC reduced the CP-induced MN
      frequencies in target (bladder) cells of mice by 41-71% in all cases. The
      modifying effects of vitamin C and NAC against CP-induced genotoxic damage may be
      due to their antioxidant, nucleophilic properties and to the ability to act as
      precursors of glutathione.

PMID- 20148458
TI  - Fine needle aspiration cytology in the diagnosis of head and neck masses:
      accuracy and diagnostic problems.
AB  - PURPOSE: Fine needle aspiration (FNA) cytology is an established technique
      associated with minimal complications compared with more invasive techniques such
      as wide core needle biopsy or open biopsy, and as such, very suitable for
      obtaining material in the delicate region of head and neck (H&N). The aim of this
      study was to assess the diagnostic accuracy of FNA cytology H&N masses. METHODS:
      Aspirations were performed by cytologists using 25 or 27G needles with 20 ml
      syringes attached, and smears were stained with May-Grunwald-Giemsa. Four hundred
      and ninety-four patients with palpable H&N masses underwent FNA during the study
      period of 2 years. RESULTS: Based on cytology alone, the most common findings
      were reactive lymphoid hyperplasia (28.5%), metastatic carcinoma (22.7%) and
      lymphoma (13.4%). Sixty-four (12.6%) FNA specimens were inadequate for diagnosis.
      Histological correlation was available in 164 (33.2%) patients who went on to
      have surgical excision of the mass. Nondiagnostic aspirate was in 16 (9.75%)
      patients, so the final group for cyto- histological correlation included 148
      patients. The overall accuracy rate of FNA cytology, whether malignant or benign,
      was 91.89%, while the diagnostic accuracy for the exact type of tumor was 87.16%.
      There were 3 (2%) false-positive (FP) and 9 (6.1%) false-negative (FN)
      cytological diagnoses. The sensitivity and specificity of FNA cytology in
      determining a malignant diagnosis were 91.5% and 92.85%, respectively. Positive
      (PPV) and negative predictive value (NPV) were 97 and 81.25%, respectively.
      CONCLUSION: Our results showed that FNA cytology is a simple, safe, and cost
      effective diagnostic method, suitable as a first-line investigation in palpable
      H&N masses. The main causes of the wrong diagnoses were sampling errors,
      inexperience and misinterpretation.

PMID- 20148459
TI  - Radioisotopic detection of sentinel lymph nodes in clinically localized high-risk
      prostate cancer.
AB  - PURPOSE: To explore the efficacy of a radioisotopic (RI) method in detecting
      sentinel lymph nodes (SLNs), known as sites of harboring metastases, in localized
      high-risk prostate cancer (HRPC). METHODS: The RI method was applied to 26 males
      with clinically localized HRPC, subjected to radical prostatectomy in 2006-2008.
      All had poor pathological characteristics: initial PSA > 15 ng/ml, Gleason score
      > 7, clinically suspected extracapsular extension, seminal vesicle invasion,
      and/or positive pelvic lymph nodes (LNs). The radiopharmaceutical (Tc-99m) was
      injected preoperatively at 4 zones of the periphery of the prostate. Tc-99m
      nanocolloid particles were <or= 80 nm in size, with total activity of 3 mCi (111
      MBq), diluted in 2 mL. One hour after Tc-99m administration, a planar
      scintigraphy was performed on a gamma camera in anterior, posterior and lateral
      projections. A high resolution collimator was used, gathering impulses up to
      300,000 per frame. The precise location of the SLNs was determined
      intraoperatively by a gamma probe. The LNs removed by extended pelvic
      lymphadenectomy were arranged on an anatomical template, examined ex vivo by the
      gamma probe and scanned again. The LNs were cleaned from the adjacent fatty
      tissue, fixed in neutral formalin, and then processed separately for histological
      and immunohistochemical examination. RESULTS: The number of surgically removed
      LNs ranged from 9 to 38 (mean 13), and the SLNs from 1 to 7 (mean 3). The SLNs
      were visualized on lymphoscintigraphy as strictly defined, round zones of high
      activity and were easily recognized intraoperatively by the gamma probe. The
      scintigraphic images of the scanned anatomical templates correlated well with
      those prior to surgery. Histology confirmed LN metastases in 11 cases. 94% of the
      metastatic LNs were SLNs, accurately detected by the RI method. Only 2 metastatic
      LNs showed no activity prior to, and during the operation. Most of the metastatic
      LNs (62%) were SLNs, located out of the obturator fossa. CONCLUSION: The
      radioisotopic detection of the SLNs in HRPC is an objective and sensitive method
      that aids the surgeon to take a proper decision regarding the scope of the pelvic
      LN dissection in each particular case.

PMID- 20148460
TI  - Linear trend analysis of patients with cervical cancer treated at the Institute
      of Oncology Vojvodina in 2001-2007.
AB  - PURPOSE: Cervical cancer is the leading cause of death in women with
      gynecological cancers in Vojvodina. Serbia currently holds the leading place in
      Europe regarding the incidence of cervical carcinoma and comes second in terms of
      mortality. METHODS: Data were retrieved from the Register for malignant neoplasms
      of the Institute of Oncology Vojvodina for the period 2001-2007. The patients
      were divided in 3 groups according to the stage of disease based on the FIGO
      classification for cervical cancer. Data were analysed using linear trend and t
      test. RESULTS: The linear trend of the number of registered cases in the group of
      stage I-IIA patients during 7 years showed no significant change in the
      prevalence of the disease. In the group of women diagnosed with stage IIB no
      statistical difference regarding either a rising or a decreasing trend was
      observed. The observed trend in an advanced disease stage (III and IV) showed a
      slight decrease in the number of patients, but without statistical significance.
      CONCLUSION: The linear trend of the number of patients with cervical carcinoma
      during a 7-year period points to the fact that the number of newly detected cases
      of advanced disease stages did not decrease significantly despite the affordable
      and simple methods of early detection. This result underlines the importance of
      implementation of a National screening programme in the general population for
      early detection of cervical neoplasms. The excellent results of National
      screening programmes in other European countries lend support to this approach.

PMID- 20148461
TI  - Quality of life and difficulties of patients encountered after autologous stem
      cell transplantation.
AB  - PURPOSE: To assess the quality of life (QoL) and difficulties of patients
      encountered after (at least day 100+) autologous stem cell transplantation
      (ASCT). METHODS: Patients from 4 bone marrow transplantation (BMT) centers in
      Ankara formed the study group. Data were collected via a socio-demographic form,
      the European Organization for Research and Treatment of Cancer (EORTC) Quality of
      Life Questionnaire-Core 30 (QLQ-C30), the Long-term BMT recovery questionnaire
      and a specific questionnaire adapted from Bush BMT Symptom Inventory for
      measuring symptom severity and symptom distress related to ASCT. Out of 114
      eligible patients 67 (58.8%) responded the questionnaires and were included in
      the study. RESULTS: The mean time elapsed since transplantation was 16.1 months
      (range 4-43). Sixteen (23.9%) patients returned to work after transplantation;
      the mean time from transplantation to active work was 8 months. The symptoms
      experienced most, interfering with the patients' daily activities related to ASCT
      were fatigue, dental problems, hair loss, tingling sensation /numbness in hands
      and feet, mouth/throat problems, taste alterations, cough and skin problems. The
      majority of them reported fear of infection and disease relapse. Sexual
      dysfunctions, difficulty of concentration and difficulties of maintaining
      religious activities were also reported. 76% of patients reported their current
      QoL was the same or better than before transplantation and rated their current
      health-related QoL as good to excellent (mean 64.5). Financial difficulties,
      fatigue, sleeping problems, and pain were the factors most rated affecting QoL.
      CONCLUSION: Fear of disease relapse, economical problems and difficulties with
      physical activities were reported as the most difficult factors to deal with
      after transplantation, showing the importance of creating multidisciplinary
      teamwork for these groups of patients.

PMID- 20148462
TI  - The level of satisfaction in cancer patients with completed treatments: a 7-year
      screening.
AB  - PURPOSE: Cancer patients encounter many problems in the post-diagnosis period and
      they want to establish a good contact with the treatment team in order to get
      better information about their condition. This study attempted to investigate in
      patients with completed treatment the level of satisfaction they derived from the
      treatment and the treatment team. METHODS: The archive of medical records of the
      Medical Oncology Department comprising 4622 patients was randomly screened
      between the years 2000 and 2006. Charts of 528 patients were reached via phone
      and analysed for clinical data. RESULTS: Approximately 78.8% of the patients had
      been informed about their malignant diseases. The rates of satisfaction from the
      treatment team, the treatment itself, and communication with the physician was
      higher among informed patients compared to uninformed ones (p<0.05). Of all the
      evaluated patients, 38.5% had been recommended to practise general exercises.
      CONCLUSION: The great majority of our patients were informed about their diseases
      and treatments, although without being given adequate importance, and the
      satisfaction rates were higher among informed patients. We believe that our study
      will provide new approaches in relation to the importance and methods of
      communicating with and informing patients.

PMID- 20148463
TI  - Undergraduate nursing students' views on Oncology. A case study in Greece.
AB  - PURPOSE: To investigate the views of undergraduate nursing students at the Patras
      Higher Technological Education Institution (HTEI), Greece, on the subject of
      Nursing Oncology, as well as their attitudes towards cancer. METHODS: In total,
      105 students of the last year participated in the study. All participants were
      anonymously administered a specifically designed questionnaire including various
      educational and practical training aspects. RESULTS: Data analysis revealed
      inadequacies in Oncology education and highlighted the need for improving
      preclinical training and developing students' skills with regard to patients'
      care and the management of various psychological and ethical issues. Furthermore,
      suggestions were made for increasing Oncology teaching staff, cooperation among
      subject specialists, increasing the hours devoted to Nursing Oncology, enhancing
      the basic and clinical courses, and introducing new subjects in the undergraduate
      curriculum. CONCLUSION: In conclusion, a well-organized Nursing Oncology
      education at the Nursing School of Patras HTEl should combine the theoretical
      background with practical training so as to prevent fragmentation of Oncology as
      an independent subject and its incorporation into other disciplines.

PMID- 20148464
TI  - IgG-lambda secreting B-lymphoplasmacytic lymphoma with disseminated cutaneous
      infiltration: report of a rare case.
AB  - We present an 85-year-old female with IgG-lambda lymphoplasmacytic lymphoma (LPL)
      with disseminated cutaneous infiltration during disease progression, 9 months
      after initial diagnosis. The patient was voluntarily undertreated, therefore the
      disease progressed with vast cutaneous involvement. The patient died from severe
      sepsis and disseminated intravascular coagulation due to acute respiratory
      bacterial infection, before receiving any kind of treatment.

PMID- 20148465
TI  - Association of endometriosis with family history of non-Hodgkin's lymphoma:
      presentation of 10 cases.
AB  - PURPOSE: Women with endometriosis have been reported to be at increased risk of
      developing non-Hodgkin's lymphoma (NHL). The purpose of this article was to
      investigate the familial risk of NHL in women with endometriosis. We report on 10
      cases with endometriosis and positive family history of NHL. METHODS: The medical
      records of 405 women with endometriosis and 200 without endometriosis were
      retrospectively analysed. All of the cases were diagnosed by laparoscopy. Ten
      cases of endometriosis having first-degree relatives with NHL are reported.
      RESULTS: We found no case with endometriosis and NHL. In contrast, we found
      10/405 (2.5%) women with endometriosis and first-degree relatives with NHL. Their
      mean age was 38.3 years (range 29-46). The main complaint was infertility. The
      mean age at onset of endometriosis was 32 years (range 22-43). The stages of
      endometriosis were: stage II (n=4), stage III (n=2) and stage IV (n=4). All of
      these patients had first-degree relatives with a history of NHL. Five had mothers
      with NHL, 5 had fathers and one had a sister. CONCLUSION: These cases could
      suggest a link between a family history of NHL and subsequent development of
      endometriosis in the first-generation women. Moreover, there was no evidence of
      association between endometriosis and NHL.

PMID- 20148466
TI  - Primary pure small cell carcinoma of the urinary bladder that responded to
      carboplatin plus etoposide: a case report and review of the literature.
AB  - Primary pure small cell carcinoma of the urinary bladder (SCCB) is an extremely
      rare tumor and accounts for less than 1% of all malignant tumors of the urinary
      bladder. This tumor exhibits more aggressive behavior than bladder transitional
      cell carcinoma. Unfortunately, optimal treatment strategy for this malignancy is
      still unknown. We present a patient with metastatic primary pure SCCB (stage IV)
      who responded to carboplatin plus etoposide combination chemotherapy and discuss
      the relevant current literature.

PMID- 20148467
TI  - Diagnostic value of serum tumor markers in asymptomatic individuals.
AB  - PURPOSE: Tumor markers, particularly carcinoembryonic antigen (CEA) and alpha
      fetoprotein (AFP), are widely used in oncology, either in monitoring patients
      with metastatic colorectal cancer (CEA) or surveillance of hepatocellular
      carcinoma (HCC/AFP). The objective of this study was to determine the diagnostic
      value of CEA, CA19-9 or AFP in asymptomatic individuals. METHODS: 12 asymptomatic
      individuals (6 males), with age range 55-82 years, referred to outpatient
      Gastroenterology- Oncology department for second opinion, with slightly elevated
      serum CEA (8 persons), CA19-9 (2 persons), and AFP (2 persons). The tumor markers
      were ordered from the primary practitioner or internist in order to avoid further
      specific examinations, such as colonoscopy. All individuals were totally
      asymptomatic. One of them had a known-history of 5-year surgically removed
      malignant pediculated sigmoid polyp and remained asymptomatic since then.
      RESULTS: After continuous and repeated meticulous examinations in all
      individuals, no specific pathology was found to explain the slightly elevated
      tumor markers. In one male (59 years) and one female (75 years) with slightly
      elevated CEA levels, 2 small colonic polyps were found, which were endoscopically
      removed. Repeated CEA levels 3 months later remained borderline high. During
      follow-up, 3 years after the discovery of slightly elevated tumor markers all
      individuals remained asymptomatic (positive predictive value / PPV 0%).
      CONCLUSION: Although further prospective studies are necessary, the preliminary
      results of this study showed that tumor markers are not useful for primary
      prevention of gastrointestinal malignancy. Moreover, slightly elevated tumor
      markers are confusing, leading to unnecessary examinations and stress from the
      individual's point of view.

PMID- 20148468
TI  - Low dose chemotherapy in combination with insulin for the treatment of advanced
      metastatic tumors. Preliminary experience.
AB  - Toxic effects and chemoresistance are serious problems concerning chemotherapy
      administration. Until now adequate solutions have not been found. In the past few
      years, while searching for possibilities to decrease toxicity, chemotherapy given
      in low, frequent doses - a novel strategy called "metronomic" administration -
      showed promising results. There is also another method for applying low doses of
      chemotherapeutics at short intervals, called Insulin Potential Therapy (IPT). It
      combines standard chemotherapy schemes, using lower doses of anticancer drugs and
      the hormone insulin which is administered intravenously (i.v.). We present hereby
      3 cases of our original practice, which demonstrate the efficiency of IPT in the
      treatment of metastatic tumors, following failure of standard chemotherapy.

PMID- 20148469
TI  - Metastatic melanoma: case report of a patient with seventeen months of complete
      remission, five years survival and review of the literature.
AB  - Melanoma, an aggressive, therapy-resistant malignancy of melanocytes, is the most
      serious type of skin cancer affecting young and middle-aged people. Therapy for
      early disease is predominantly surgical, with a minor benefit noted with the use
      of adjuvant therapy. Management of systemic melanoma is a challenge because of a
      paucity of active treatment modalities. The authors present the case of a patient
      with advanced-stage melanoma who underwent surgery for metastatic disease. He
      then received cisplatin-based combination chemotherapy, with disease
      stabilization. However, after different regimen modifications complete remission
      (CR) was finally achieved, until the disease progressed once more. Five years
      after surgery, the patient is still alive and continuing chemotherapy.

PMID- 20148470
TI  - Primary peritoneal spindle cell sarcoma presented with massive ascites: a case
      report.
AB  - Soft tissue sarcomas (STSs) are a heterogeneous group of rare neoplasms
      originating from the embryonic mesoderm and mesenchymal cells. Primary peritoneal
      sarcomas have been reported as leiomyosarcoma, liposarcoma and carcinosarcoma.
      However, primary peritoneal spindle cell sarcoma has never been reported in the
      literature. Herein, we report on a 38-year-old woman with massive ascites
      diagnosed as primary peritoneal spindle cell sarcoma. Following doxorubicin and
      ifosfamide chemotherapy, her symptoms improved and ascites regressed. Other
      primary peritoneal sarcomas rarely cause massive ascites. We suggest that in
      patients presenting with massive exudative ascites associated with malignancy,
      primary peritoneal sarcomas should be also considered in the differential
      diagnosis.

PMID- 20148472
TI  - Acute renal failure and multiple extranodal involvement in a patient with diffuse
      large B cell lymphoma.

PMID- 20148471
TI  - Emphysematous pyelonephritis in a female with diabetes mellitus, renal calculi,
      breast cancer and chemotherapy-induced lymphopenia, successfully managed without
      nephrectomy.

PMID- 20148473
TI  - Renal cell carcinoma with pulmonary metastasis misdiagnosed as other primary
      malignant tumor.

PMID- 20148474
TI  - Cure of gemcitabine-induced systemic capillary leak syndrome without
      corticosteroids.

PMID- 20148475
TI  - Delayed reaction after adjuvant whole breast radiotherapy at the dose of 42.9 Gy
      in 13 fractions over 5 weeks: the need for rapid post irradiation clinical
      assessment and who are the patients at risk?

PMID- 20148476
TI  - Bernard Peyrilhe (1737-1804) and the first experimental transmission of cancer.
AB  - Professor Bernard Peyrilhe occupied the chairs of surgical chemistry and medica
      materia at the Faculty of Medicine of Paris. He was a great surgeon, cancer
      specialist and historian of medicine. He led in depth studies on cancer and
      realized the first experimental transmission of cancer by injecting extracts of
      breast cancer into an animal.

PMID- 20148477
TI  - Vegetarian diets may prevent & treat some chronic diseases.  Plant-based diets
      can meet all current nutrient needs and may lessen disease risk.

PMID- 20148478
TI  - Brief stroke symptoms precede sever strokes only 1 in 8 times.  Transient
      ischemic attacks--TIAs--are a warning for the real thing, but seven of eight
      strokes occur without warning symptoms.

PMID- 20148479
TI  - Bone formation, bone loss prevention.  Recent research may have found new
      pathways for targeted therapies to fight osteoporosis.

PMID- 20148480
TI  - Anxiety, depression and other mental disorders are fairly common.  At some point
      a majority of us will experience some form of mental illness, if only for a short
      time.

PMID- 20148481
TI  - New weapons against kidney cancer. Two recent drug options appear to extend
      survival for kidney cancer patients who can't tolerate existing medications.

PMID- 20148483
TI  - Health tips.  Outsmart your supermarket.

PMID- 20148482
TI  - My wife suffers terribly from SAD (seasonal affective disorder). Other than light
      therapy, are there any other treatments that could help get her through the
      dreary winter months?

PMID- 20148484
TI  - Stopping proton pump inhibitor use may cause heartburn.

PMID- 20148485
TI  - What's in your medicine cabinet?  It could save you a trip to the doctor.

PMID- 20148486
TI  - Spice up your rice.  New look at an old grain.

PMID- 20148487
TI  - My husband uses a rub-on prescription testosterone gel for low testosterone.  I
      always remind him to wash his hands after he uses it.  He says I'm overreacting. 
      Am I?

PMID- 20148490
TI  - Physicians should conduct pretravel consultations.

PMID- 20148491
TI  - Recognizing patients' transitions toward the end of their life.

PMID- 20148492
TI  - Physicians should use resources to find clinical answers.

PMID- 20148493
TI  - Chagas disease as secondary cause of cardiomyopathy.

PMID- 20148494
TI  - Uncharted territory.

PMID- 20148495
TI  - Adolescent dating violence.

PMID- 20148496
TI  - FPIN's clinical inquiries. Combination therapy for postmenopausal osteoporosis.

PMID- 20148497
TI  - Osteoarthritis of the hip.

PMID- 20148499
TI  - Primary care for children with autism.
AB  - The earliest sign of autism in children is the delayed attainment of social skill
      milestones, including joint attention, social orienting, and pretend play.
      Language impairment is a common, but less specific, sign of autism. Repetitive
      behaviors and restricted interests may not be noted until after social skill and
      communication impairments are exhibited. Physicians should perform developmental
      surveillance at all well-child visits, and the American Academy of Pediatrics
      recommends administering an autism-specific screening tool at the 18- and 24
      month visits. A referral for comprehensive diagnostic evaluation is appropriate
      if concerns arise from surveillance, screening, or parental observations. The
      goals of long-term management are to maximize functional independence and
      community engagement, minimize maladaptive behaviors, and provide family and
      caregiver support. Physicians play an important role in coordinating care through
      an interdisciplinary team; referring families for specialized services; and
      treating children's associated conditions, including sleep disturbances,
      gastrointestinal problems, anxiety, and hyperactivity. Autism is a lifelong
      condition, but early recognition, diagnosis, and treatment can improve the
      prognosis, whereas associated medical conditions, psychiatric conditions, and
      intellectual disability can worsen the prognosis.

PMID- 20148500
TI  - Health effects of hawthorn.
AB  - Hawthorn medicinal extract has long been a favored herbal remedy in Europe. The
      active components of this slow-acting cardiotonic agent are thought to be
      flavonoids and oligomeric procyanidins. The most studied hawthorn extracts are WS
      1442 and LI 132. Reviews of placebo- controlled trials have reported both
      subjective and objective improvement in patients with mild forms of heart failure
      (New York Heart Association classes I through III). Other studies of hawthorn in
      patients with heart failure have revealed improvement in clinical symptoms,
      pressure-heart rate product, left ventricular ejection fraction, and patients'
      subjective sense of well-being. However, there is no evidence of a notable
      reduction in mortality or sudden death. Hawthorn is well tolerated; the most
      common adverse effects are vertigo and dizziness. Theoretic interactions exist
      with antiarrhythmics, antihypertensives, digoxin, and antihyperlipidemic agents.
      Proven conventional therapies for heart failure are still recommended until the
      safety and effectiveness of hawthorn has been proven in long-term studies.

PMID- 20148501
TI  - Evaluation and treatment of severe asymptomatic hypertension.
AB  - Poorly controlled hypertension is a common finding in the outpatient setting.
      When patients present with severely elevated blood pressure (i.e., systolic blood
      pressure of 180 mm Hg or greater, or diastolic blood pressure of 110 mm Hg or
      greater), physicians need to differentiate hypertensive emergency from severely
      elevated blood pressure without signs or symptoms of end-organ damage (severe
      asymptomatic hypertension). Most patients who are asymptomatic but have poorly
      controlled hypertension do not have acute end-organ damage and, therefore, do not
      require immediate workup or treatment (within 24 hours). However, physicians
      should confirm blood pressure readings and appropriately classify the
      hypertensive state. A cardiovascular risk profile is important in guiding the
      treatment of severe asymptomatic hypertension; higher risk patients may benefit
      from more urgent and aggressive evaluation and treatment. Oral agents may be
      initiated before discharge, but intravenous medications and fast-acting oral
      agents should be reserved for true hypertensive emergencies. High blood pressure
      should be treated gradually. Appropriate, repeated follow-up over weeks to months
      is needed to reach desired blood pressure goals.

PMID- 20148502
TI  - Preterm labor.
AB  - Preventing preterm delivery remains one of the great challenges in modern
      medicine. Preterm birth rates continue to increase and accounted for 12.7 percent
      of all U.S. births in 2005. The etiology of preterm delivery is unclear, but is
      likely to be complex and influenced by genetics and environmental factors. Women
      with previous preterm birth are at increased risk of subsequent preterm delivery
      and may be candidates for treatment with antenatal progesterone. Fetal
      fibronectin testing and endovaginal ultrasonography for cervical length are
      useful for triage. For the patient in preterm labor, only antenatal
      corticosteroids and delivery in a facility with a level III neonatal intensive
      care unit have been shown to improve outcomes consistently. Tocolytic agents may
      delay delivery for up to 48 hours, enabling the administration of antenatal
      corticosteroids or maternal transfer. Routine use of antibiotics in preterm labor
      is not indicated except for group B streptococcus prophylaxis or treatment of
      chorioamnionitis.

PMID- 20148503
TI  - Sexual assault of women.
AB  - Sexual violence affects up to one third of women during their lifetime. Sexual
      assault is underreported, and more than one half of assaults are committed by
      someone known to the survivor. Although both men and women can be sexually
      assaulted, women are at greatest risk. Some groups are more vulnerable, including
      adolescents; survivors of childhood sexual or physical abuse; persons who are
      disabled; persons with substance abuse problems; sex workers; persons who are
      poor or homeless; and persons living in prisons, institutions, or areas of
      military conflict. Family physicians care for sexual assault survivors
      immediately and years after the assault. Immediate care includes the treatment of
      injuries, prophylaxis for sexually transmitted infections, administration of
      emergency contraception to prevent pregnancy, and the sensitive management of
      psychological issues. Family physicians should collect evidence for a "rape kit"
      only if they are experienced in treating persons who have been sexually assaulted
      because of the legal ramifications of improper collection and storage of
      evidence. Sexual assault may result in long-term mental and physical health
      problems. Presentations to the family physician may include self-destructive
      behaviors, chronic pelvic pain, and difficulty with pelvic examinations.
      Prevention of sexual assault is societal and should focus on public health
      education. Safety and support programs have been shown to reduce sexual assaults.

PMID- 20148504
TI  - Screening for hepatitis B virus infection in pregnancy: reaffirmation
      recommendation statement.

PMID- 20148505
TI  - Screening for asymptomatic bacteriuria in adults: reaffirmation recommendation
      statement.

PMID- 20148506
TI  - Screening for asymptomatic bacteriuria in adults.

PMID- 20148507
TI  - Discrete papules on the thigh of a child. Molluscum contagiosum.

PMID- 20148508
TI  - Chronic rash associated with numbness. Hansen disease (leprosy).

PMID- 20148510
TI  - Molecular dynamics analysis of the conformations of a beta-hairpin miniprotein.
AB  - Molecular dynamics simulations of a beta-hairpin miniprotein, CLN025, were
      performed to examine the conformational stability of the peptide in H(2)O at 278,
      300, 333, and 363 K, as well as in TFE, MeOH, and DMSO at 300 K. CLN025 is a
      variant of the Chignolin miniprotein, in which the terminal Gly residues of
      Chignolin are replaced with Tyr residues, which leads to a 29.7 K increase in
      melting temperature. The energy of the intramolecular interactions was calculated
      using DFT quantum chemical calculations at the BHandHLYP/cc-pVTZ level of theory.
      CLN025 maintained a beta-hairpin conformation in all environments. The beta
      hairpin is stabilized by hydrogen bonds, an electrostatic interaction between the
      charged termini of the peptide, and weakly polar interactions. The interaction
      between the backbones of the N and C-terminal strands accounts for -97.32 to 
      120.87 kcal mol(-1) of the stabilization energy. The energies of the CH-pi
      interactions between Tyr2 and Pro4 were between -1.80 and -8.9 kcal mol(-1), and
      the energy of the Tyr2-Trp9 Ar-Ar interaction was between -0.43 and -8.11 kcal
      mol(-1). Increasing temperature caused the Tyr2-Pro4 CH-pi and the Tyr2-Trp9 and
      Tyr2-Tyr10 Ar-Ar interactions to become less favorable, but the Tyr1-Trp9
      interaction became more favorable and played an important role in stabilizing the
      beta-hairpin of CLN025 that resulted in the increased melting temperature. Weakly
      polar interactions play an important role in the structure and stability of
      CLN025 and other proteins.

PMID- 20148511
TI  - Isomer-dependent adsorption and release of cis- and trans-platin anticancer drugs
      by mesoporous silica nanoparticles.
AB  - We report on adsorption and release of the anticancer drugs cisplatin and
      transplatin from mesoporous silica nanomaterials, emphasizing the differences
      between cisplatin and its much less toxic isomer. Two types of particles, MCM-41
      and SBA-15, were used, either as just synthesized or after calcination to remove
      the templates. The particles were characterized by TEM, nitrogen physisorption,
      and elemental analysis. The UV-vis spectra of cisplatin and transplatin were
      obtained and the intensities of several bands (205-210 nm, 210-220 nm, 220-235
      nm, and 300-330 nm) were found proportional to drug concentrations, allowing
      their use for measuring drug concentration. To evaluate drug adsorption by
      nanoparticles, nanoparticles were incubated in drug solutions and removed by
      centrifugation, after which the supernatants were scanned by spectrometer to
      determine drug remaining. It was found that calcined MCM adsorbed less cisplatin
      or transplatin per particle than as-synthesized MCM. SBA nanoparticles adsorbed
      slightly more cisplatin than MCM, and slightly less transplatin. Measurements of
      drug adsorption as a function of time show that drug is rapidly adsorbed by all
      particles studied. This rapid adsorption is probably associated with adsorption
      of drug on the external surfaces of the particles as well as the possible
      physisorption within the surfactant assemblies or by replacing the surfactant
      molecules or ions in the case of the as-synthesized materials. For calcined SBA
      particles, it is followed by a slow take-up of drug, perhaps due to the internal
      pores. There is no slow take-up by as-synthesized SBA particles or by either as
      synthesized or calcined MCM particles. Measurement of the release of platinum
      drugs from nanoparticles previously soaked in drug solutions showed a substantial
      quick release for all particles and both drugs. This was followed by a slow
      release of Pt species in the case of transplatin in calcined SBA.

PMID- 20148512
TI  - Dye-sensitized solar cells: driving-force effects on electron recombination
      dynamics with cobalt-based shuttles.
AB  - A series of cobalt-containing redox couples, based on [Co(1,10
      phenanthroline)(3)](ClO(4))(2) and its derivatives, were prepared for use as
      regenerators/shuttles in dye-sensitized solar cells featuring modified TiO(2)
      photoelectrodes. Surface modification and trap-state passivation of the TiO(2)
      nanoparticle film electrodes were accomplished via atomic layer deposition of an
      ultrathin alumina coating. Electron lifetimes were then extracted from open
      circuit voltage decay measurements. Cells employing alumina barrier/passivation
      layers exhibited higher open-circuit voltages as shuttles with more positive
      redox potentials were used, with the Co(5-nitro-phen)(3)(3+/2+) couple exhibiting
      the highest V(oc) (0.844 V). Analysis of the open-circuit voltages and electron
      lifetimes indicate Marcus normal-region behavior for back electron transfer from
      the TiO(2) photoanode to these compounds.

PMID- 20148513
TI  - Influence of soil factors on the dissipation of a new pyrimidynyloxybenzoic
      herbicide ZJ0273.
AB  - A novel pyrimidynyloxybenzoic herbicide (ZJ0273) uniformly labeled with (14)C on
      the benzoate ring was applied to soils under sterile and nonsterile conditions to
      understand the effect of soil microorganisms and selected properties on its
      dissipation and transformations to bound resides and (14)CO(2). A significant
      effect of soil microorganisms was found in an acidic soil, where sterilization
      significantly prolonged the half-dissipation time (DT(50)) of ZJ0273 from 15.57
      to 34.31 days and decreased the total amount of mineralized (14)CO(2) from 19.91
      to 0.43%. However, sterilization showed limited effect on the patterns of bound
      residue or extractable residue levels in soils having pH > or = 6.1. In addition,
      a significant suppression of high pH was found on the dissipation of extractable
      residues and formation of bound residues. The enhancement of bound residue
      formation by low soil pH was attributed to increased conversion of ZJ0273 to its
      intermediates, which were rapidly bound to soil organic matter.

PMID- 20148514
TI  - Purified blueberry anthocyanins and blueberry juice alter development of obesity
      in mice fed an obesogenic high-fat diet.
AB  - Male C57BL/6J mice (25 days of age) were fed either a low-fat diet (10% kcal from
      fat) (LF) or a high-fat diet (45% kcal from fat) (HF45) for a period of 72 days.
      Blueberry juice or purified blueberry anthocyanins (0.2 or 1.0 mg/mL) in the
      drinking water were included in LF or HF45 treatments. Sucrose was added to the
      drinking water of one treatment to test if the sugars in blueberry juice would
      affect development of obesity. Total body weights (g) and body fat (%) were
      higher and body lean tissue (%) was lower in the HF45 fed mice compared to the LF
      fed mice after 72 days, but in mice fed HF45 diet plus blueberry juice or
      blueberry anthocyanins (0.2 mg/mL), body fat (%) was not different from those
      mice fed the LF diet. Anthocyanins (ACNs) decreased retroperitoneal and
      epididymal adipose tissue weights. Fasting serum glucose concentrations were
      higher in mice fed the HF45 diet. However, it was reduced to LF levels in mice
      fed the HF45 diet plus 0.2 mg of ACNs/mL in the drinking water, but not with
      blueberry juice. beta cell function (HOMA-BCF) score was lowered with HF45
      feeding but returned to normal levels in mice fed the HF45 diet plus purified
      ACNs (0.2 mg/mL). Serum leptin was elevated in mice fed HF45 diet, and feeding
      either blueberry juice or purified ACNs (0.2 mg/mL) decreased serum leptin levels
      relative to HF45 control. Sucrose in drinking water, when consumption was
      restricted to the volume of juice consumed, produced lower serum leptin and
      insulin levels, leptin/fat, and retroperitoneal and total fat (% BW). Blueberry
      juice was not as effective as the low dose of anthocyanins in the drinking water
      in preventing obesity. Additional studies are needed to determine factors
      responsible for the differing responses of blueberry juice and whole blueberry in
      preventing the development of obesity.

PMID- 20148515
TI  - Subcritical solvent extraction of anthocyanins from dried red grape pomace.
AB  - Accelerated solvent extraction (ASE) was used to optimize and determine the
      effectiveness of an alternative, environmentally friendly extraction procedure
      using subcritical solvents to recover anthocyanins from freeze-dried, ground
      Sunbelt red grape pomace. Anthocyanins were extracted from pomace using the
      following ASE variables: pressure (6.8 MPa), one extraction cycle, and
      temperature (40, 60, 80, 100, 120, and 140 degrees C). Conventional solvent
      extraction with methanol/water/formic acid (60:37:3 v/v/v) was compared to four
      hydroethanolic solvents (10, 30, 50, and 70% ethanol in water, v/v). Anthocyanins
      in the extracts were identified and quantified by HPLC-MS and HPLC. There was an
      insignificant interaction between solvent and temperature (p = 0.0663). Solvents
      containing 70 and 50% ethanol in water extracted more total anthocyanins (463 and
      455 mg/100 g of DW, respectively) than other solvents. The total amounts of
      anthocyanins extracted at 100 degrees C (450 mg/100 g of DW), 80 degrees C (436
      mg/100 g of DW), and 120 degrees C (411 mg/100 g of DW) were higher than at the
      other temperatures. Solvents containing 70 and 50% ethanol in water extracted
      similar amounts of anthocyanins as conventional extraction solvent.

PMID- 20148516
TI  - Introduction of 4-chloro-alpha-cyanocinnamic acid liquid matrices for high
      sensitivity UV-MALDI MS.
AB  - Matrix-assisted laser desorption/ionization (MALDI) is a key ionization technique
      in mass spectrometry (MS) for the analysis of labile macromolecules. An important
      area of study and improvements in relation to MALDI and its application in high
      sensitivity MS is that of matrix design and sample preparation. Recently, 4
      chloro-alpha-cyanocinnamic acid (ClCCA) has been introduced as a new rationally
      designed matrix and reported to provide an improved analytical performance as
      demonstrated by an increase in sequence coverage of protein digests obtained by
      peptide mass mapping (PMM) (Jaskolla, T. W.; et al. Proc. Natl. Acad. Sci. U.S.A.
      2008, 105, 12200-12205). This new matrix shows the potential to be a superior
      alternative to the commonly used and highly successful alpha-cyano-4
      hydroxycinnamic acid (CHCA). We have taken this design one step further by
      developing and optimizing an ionic liquid matrix (ILM) and liquid support matrix
      (LSM) using ClCCA as the principle chromophore and MALDI matrix compound. These
      new liquid matrices possess greater sample homogeneity and a simpler morphology.
      The data obtained from our studies show improved sequence coverage for BSA
      digests compared to the traditional CHCA crystalline matrix and for the ClCCA
      containing ILM a similar performance to the ClCCA crystalline matrix down to 1
      fmol of BSA digest prepared in a single MALDI sample droplet with current
      sensitivity levels in the attomole range. The LSMs show a high tolerance to
      contamination such as ammonium bicarbonate, a commonly used buffering agent.

PMID- 20148517
TI  - Strategy for studying the liver secretome on the organ level.
AB  - Secretome study presents new possibilities for understanding liver secretory
      function in a comprehensive and exploratory way. Perfusates from isolated
      perfused rat liver are good targets for liver secretome study on the organ level.
      There are two major concerns in this type of study, cytosolic and blood
      contaminations in the perfusates. Therefore, the perfusion conditions were
      carefully controlled and alanine aminotransferase levels in the perfusates were
      monitored as indicators of liver integrity and cytosolic contamination. The
      protein pattern of perfusate was significantly different from cell lysate, which
      showed low cytosolic contamination. The amount of immunoglobulins in the
      perfusates identified by both Western blot and MS/MS indicated low serum
      contamination. In total, 357 secretory protein candidates were identified by the
      Enrichment Index method or N-terminal signal peptide prediction. Secretory
      proteins annotated by Swiss-Prot were 5-fold enriched in the perfusates and
      around 10-fold enriched in the portion identified by the Enrichment Index method.
      Some cytokines, secretory proteins from liver interstitial cells, and components
      of the liver microenvironment were found in the perfusates, highlighting the
      advantages of studying the liver secretome on the organ level. The strategy can
      be used in physiology research and biomarker discovery for diseases in the liver
      as well as other organs.

PMID- 20148519
TI  - Lone pairs as chemical scissors in new antimony oxychlorides, Sb2ZnO3Cl2 and
      Sb16Cd8O25Cl14.
AB  - Two new metal antimony oxychlorides, Sb(2)ZnO(3)Cl(2) and Sb(16)Cd(8)O(25)Cl(14),
      have been synthesized by solid-state reactions using Sb(2)O(3) and ZnCl(2) (or
      CdCl(2)) as reagents. The structures of Sb(2)ZnO(3)Cl(2) and
      Sb(16)Cd(8)O(25)Cl(14) have been determined by single-crystal X-ray diffraction.
      Both of the reported materials contain Sb(3+) cations that are in an asymmetric
      coordination environment attributable to their stereoactive lone pair.
      Sb(2)ZnO(3)Cl(2) has a novel two-dimensional layered structure consisting of
      distorted ZnO(2)Cl(2) tetrahedra and SbO(3) polyhedra. Sb(16)Cd(8)O(25)Cl(14)
      exhibits a one-dimensional structure consisting of Sb(3+)-Cd(2+)-oxide rods,
      Cd(2+)-chloride double chains, and isolated Cl(-) ions. Complete separation of
      the halophile and chalcophile moieties is observed from the reported materials.
      Detailed structural analysis, IR spectra, thermogravimetric analysis, ion
      exchange reactions, and dipole moment calculations are presented. Crystal data:
      Sb(2)ZnO(3)Cl(2), orthorhombic, space group Pnma (No. 62), a = 17.124(4) A, b =
      5.5598(12) A, c = 6.4823(14) A, V = 617.2(2) A(3), and Z = 4;
      Sb(16)Cd(8)O(25)Cl(14), monoclinic, space group I2/m (No. 12), a = 14.251(3) A, b
      = 3.9895(8) A, c = 21.145(4) A, beta = 97.35(3) degrees, V = 1192.3(4) A(3), and
      Z = 8.

PMID- 20148520
TI  - The membrane-bound quinohemoprotein alcohol dehydrogenase from Gluconacetobacter
      diazotrophicus PAL5 carries a [2Fe-2S] cluster.
AB  - Gluconacetobacter diazotrophicus stands out among the acetic acid bacteria as it
      fixes dinitrogen and is a true endophyte. It has a set of constitutive enzymes to
      oxidize ethanol and acetaldehyde which is upregulated during N(2)-dependent
      growth. The membrane-bound alcohol dehydrogenase (ADH) is a heterodimer (subunit
      I approximately 72 kDa, subunit II approximately 44 kDa) and constitutes an
      important component of this organism. ADH of Ga. diazotrophicus is a typical
      quinohemoprotein with one pyrroloquinoline quinone (PQQ) and four c-type
      cytochromes. For the first time, a [2Fe-2S] cluster has been identified by EPR
      spectroscopy in this type of enzyme. This finding is supported by quantitative
      chemical analysis, revealing 5.90 +/- 0.15 Fe and 2.06 +/- 0.10 acid-labile
      sulfurs per ADH heterodimer. The X-band EPR spectrum of ADH (as isolated in the
      presence of dioxygen, 20 K) showed three broad resonances at g 2.007, 1.941, and
      1.920 (g(av) 1.956), as well as an intense narrow line centered at g = 2.0034.
      The latter signal, which was still detected at 100 K, was attributed to the PQQ
      semiquinone radical (PQQ(sq)). The broad resonances observed at lower temperature
      were assigned to the [2Fe-2S] cluster in the one-electron reduced state. The
      oxidation-reduction potentials E(m) (pH 6.0 vs SHE) of the four c-type
      cytochromes were estimated to E(m1) = -64 (+/-2) mV, E(m2) = -8 (+/-2) mV, E(m3)
      = +185 (+/-15) mV, and E(m4) = +210 (+/-10) mV (spectroelectrochemistry), E(mFeS)
      = -250 (+/-5) mV for the [2Fe-2S] cluster, and E(mPQQ) = -210 (+/-5) mV for the
      PQQ/PQQH(2) couple (EPR spectroscopy). We propose a model for the membrane-bound
      ADH of Ga. diazotrophicus showing hypothetical intra- and intermolecular electron
      pathways. Subunit I binds the PQQ cofactor, the [2Fe-2S] cluster, and one c-type
      cytochrome. Subunit II harbors three c-type cytochromes, thus providing an
      efficient electron transfer route to quinones located in the cytoplasmic
      membrane.

PMID- 20148521
TI  - Preparation of potassium alkynylaryltrifluoroborates from
      haloaryltrifluoroborates via Sonogashira coupling reaction.
AB  - A novel series of alkyne-containing potassium organotrifluoroborates were
      prepared in good yields from the corresponding haloaryltrifluoroborates and
      various alkynes via Sonogashira coupling reaction. Also, the Suzuki-Miyaura cross
      coupling reaction of alkynylaryltrifluoroborates with aryl and alkenyl bromides
      was achieved in the presence of 5 mol % of Pd(TPP)(4) and 3.0 equiv of Cs(2)CO(3)
      in aqueous 1,4-dioxane at 150 degrees C by microwave irradiation.

PMID- 20148518
TI  - Electrochemical quantification of serotonin in the live embryonic zebrafish
      intestine.
AB  - We monitored real-time in vivo levels of serotonin release in the digestive
      system of intact zebrafish embryos during early development (5 days
      postfertilization, dpf) using differential pulse voltammetry with implanted
      carbon fiber microelectrodes modified with carbon nanotubes dispersed in nafion.
      A detection limit of 1 nM, a linear range between 5 and 200 nM, and a sensitivity
      of 83.65 nA x microM(-1) were recorded. The microelectrodes were implanted at
      various locations in the intestine of zebrafish embryos. Serotonin levels of up
      to 29.9 (+/-1.13) nM were measured in vivo in normal physiological conditions.
      Measurements were performed in intact live embryos without additional
      perturbation beyond electrode insertion. The sensor was able to quantify
      pharmacological alterations in serotonin release and provide the longitudinal
      distribution of this neurotransmitter along the intestine with high spatial
      resolution. In the presence of fluvoxamine, a selective serotonin reuptake
      inhibitor (SSRI), concentrations of 54.1 (+/-1.05) nM were recorded while in the
      presence of p-chloro-phenylalanine (PCPA), a tryptophan hydroxylase inhibitor,
      the serotonin levels decreased to 7.2 (+/-0.45) nM. The variation of serotonin
      levels was correlated with immunohistochemical analysis. We have demonstrated the
      first use of electrochemical microsensors for in vivo monitoring of intestinal
      serotonin levels in intact zebrafish embryos.

PMID- 20148522
TI  - Novel and efficient chiral bisphosphorus ligands for rhodium-catalyzed asymmetric
      hydrogenation.
AB  - A series of structurally novel, operationally convenient, and efficient chiral 2
      phosphino-2,3-dihydrobenzo[d][1,3]oxaphosphole ligands was developed.
      Applications of ligands 3a and 3b in rhodium-catalyzed asymmetric hydrogenation
      of alpha-(acylamino)acrylates and beta-(acylamino)acrylates provided excellent
      enantioselectivities (up to >99% ee) and reactivities (up to 10,000 TON).

PMID- 20148523
TI  - Enantioselective total synthesis of (-)-alpha-kainic acid.
AB  - An enantioselective total synthesis of (-)-alpha-kainic acid is described. Key
      steps are an Ir-catalyzed allylic amination with a propargylic amine to provide
      an enyne and a diastereoselective intramolecular Pauson-Khand reaction.
      Subsequent steps involve a Baeyer-Villiger reaction, reduction of the resulting
      lactone, and direct Jones oxidation of a silyl ether.

PMID- 20148524
TI  - On-chip functionalization of carbon nanotubes with photosystem I.
AB  - We optoelectronically functionalize carbon nanotubes (CNTs) with the
      photosynthetic reaction center photosystem I (PSI) according to three different
      on-chip chemical routes. The PSI is bound to the CNTs via covalent, hydrogen, or
      electrostatic bonds. Our approach allows the electrical contact of single PSI-CNT
      hybrid systems where the orientation of the PSI with respect to the CNTs depends
      on the binding mechanism. Our data are consistent with the interpretation that if
      the PSI is anchored with its internal electron transport path perpendicular to
      CNTs, the optical excitation of the PSI leads to an enhanced photoconductance of
      the hybrid system.

PMID- 20148525
TI  - Total synthesis of lycogarubin C and lycogalic acid.
AB  - Two complementary concise total syntheses of lycogarubin C (1) and lycogalic acid
      (2, aka chromopyrrolic acid) are detailed utilizing a 1,2,4,5-tetrazine --> 1,2
      diazine --> pyrrole Diels-Alder strategy and enlisting acetylenic dienophiles.

PMID- 20148526
TI  - Sesquiterpene lactones from Scorzonera austriaca.
AB  - Six new sesquiterpene lactones, scorzoaustriacoside (1), scorzoaustriacin (2),
      scorzoaustriacin 3-O-beta-d-glucoside (3), 4-epi-dihydroestafiatol (4), 14
      isovaleroxyscorzoaustricin (5), and 14-isovaleroxyscorzoaustricin sulfate (6),
      along with five known guaianolides, were isolated from an acetone extract of the
      roots of Scorzonera austriaca. The structures of the new compounds were
      elucidated mainly by interpretation of their 1D and 2D NMR and HRMS data. Several
      isolates obtained in this investigation were evaluated against a small panel of
      cancer cell lines.

PMID- 20148527
TI  - Electrostatic persistence length.
AB  - The persistence length is calculated for polyelectrolyte chains with fixed bond
      lengths and bond angles (pi-theta), and a potential energy consisting of the
      screened Coulomb interaction between beads, potential wells alpha phi(i)2 for the
      dihedral angles phi(i), and coupling terms beta phi(i) phi(i+/-1). This model
      defines a librating chain that reduces in appropriate limits to the freely
      rotating or wormlike chains, it can accommodate local crumpling or extreme
      stiffness, and it is easy to simulate. A planar-quadratic (pq), analytic
      approximation is based on an expansion of the electrostatic energy in
      eigenfunctions of the quadratic form that describes the backbone energy, and on
      the assumption that the quadratic form not only is positive but also adequately
      confines the chain in an infinite phase space of dihedral angles to the
      physically unique part with all |phi(i)| < pi. The pq approximation is available
      under these weak constraints, but the simulations confirm its quantitative
      accuracy only under the expected condition that alpha is large, that is, for very
      stiff chains. Stiff chains can also be simulated with small alpha and small theta
      and compared to an OSF approximation suitably generalized to chains with finite
      rather than vanishing theta, and increasing agreement with OSF is found the
      smaller is theta. The two approximations, one becoming exact as alpha -->
      infinity with fixed theta, the other as theta --> 0 with fixed alpha, are
      quantitatively similar in behavior, both giving a persistence length P = P0 + aD2
      for stiff chains, where D is the Debye length. However, the coefficient apq is
      about twice the value of aOSF. Under other conditions the simulations show that P
      may or not be linear in D2 at small or moderate D, depending on the magnitudes of
      alpha, beta, theta, and the charge density but always becomes linear at large D.
      Even at a moderately low charge density, corresponding to fewer than 20% of the
      beads being charged, and with strong crumpling induced by large beta, increasing
      D dissolves blobs and recovers a linear dependence of P on D2, although a lower
      power of D gives an adequate fit at moderate D. For the class of models
      considered, it is concluded that the only universal feature is the asymptotic
      linearity of P in D2, regardless of flexibility or stiffness.

PMID- 20148528
TI  - Attractive and repulsive electrostatic forces between positively charged latex
      particles in the presence of anionic linear polyelectrolytes.
AB  - The interaction forces between individual positively charged amidine
      functionalized latex particles with adsorbed negatively charged sodium
      poly(styrene sulfonate) were studied with the colloidal probe technique based on
      atomic force microscopy (AFM). When the polymer dose is progressively increased,
      the strength of the repulsive force between the particles decreases as the charge
      neutralization point is approached, then increases again due to overcharging, and
      finally reaches a plateau. Surface potentials obtained from fits of the force
      profiles to Poisson-Boltzmann theory agree well with potentials measured with
      electrophoresis. Close to the charge neutralization point, attractive forces
      exceeding van der Waals interactions are found. These attractive forces increase
      in strength with increasing molecular mass of the polymer and decreasing ionic
      strength. These attractive interactions are of electrostatic origin and result
      from lateral patch-charge heterogeneities within the adsorbed polyelectrolyte
      layer. The measured forces are shown to be in semiquantitative agreement with
      model calculations based on charge distributions with square lattice symmetry.

PMID- 20148529
TI  - Role of solvent protic character on the aggregation behavior of polybenzimidazole
      in solution.
AB  - The aggregation behavior of poly(4,4'-diphenylether-5,5'-bibenzimidazole) (OPBI)
      in polar aprotic (dimethyl acetamide, DMAc) and protic (formic acid, FA) solvents
      is studied as a function of the polymer concentration and solution temperature.
      The effects of solvent protic character on the aggregation behavior of OPBI are
      elucidated. The photophysical studies suggest that the OPBI chains form
      aggregated structures in both DMAc and FA solutions when the OPBI concentration
      is increased. The dependences of the emission spectra on the polymer
      concentrations in two solvents are not similar in nature, indicating that in both
      of the solvents the aggregations are intermolecular processes, though their
      mechanisms are different owing to the polyelectrolytic nature of OPBI in FA
      medium. The triexponential decay profiles obtained from the time-resolved
      fluorescence study for the concentrated solutions (both in DMAc and FA) display a
      negative fractional coefficient and longer excited state lifetime, providing
      support for the aggregations at higher concentration. The temperature dependence
      emission spectra suggest that the aggregations in both of the solvents
      destabilize with increasing temperature. The higher activation energy of
      aggregation (E(A)) in DMAc (5.62 KJ/mol) compared with that in FA (3.07 kJ/mol)
      reveals that the aggregation formation pathways are different in two solvents and
      stronger aggregates are formed in the former solvent. The dilute solution
      viscometry (DSV) studies demonstrate that the OPBI chains adapt a bigger extended
      conformation in FA compared with DMAc owing to the stronger intramolecular chain
      repulsion in FA arising due to the polyelectrolyte nature of OPBI in this
      solvent. A conformation transition of OPBI chains from compact collapsed to
      extended conformer is observed in DMAc solvent with increasing concentration,
      whereas any such transition is absent in FA medium. Transmission electron
      microscope (TEM) images and circular dichroism (CD) spectra are also in agreement
      with the presence of a conformational transition in DMAc and the absence of it in
      FA. The temperature dependent DSV studies further support the disruption of
      aggregated structure with increasing temperature in both of the solvents. DSV
      studies exhibit that the deaggregation is driven by a conformation transition
      (extended to compact collapsed) in DMAc, whereas in FA the disruption happens
      without conformational transition.

PMID- 20148530
TI  - Interaction of bovine serum albumin with cationic single chain+nonionic and
      cationic gemini+nonionic binary surfactant mixtures.
AB  - The interaction of bovine serum albumin (BSA) with cetyltrimethylammonium bromide
      (CTAB), C(16)C(4)C(16)Br(2), Brij58, and their binary mixtures has been studied
      using tensiometry, spectrofluorometry, and circular dichroism at physiological pH
      and 25 degrees C. The tensiometric profiles of CTAB and C(16)C(4)C(16)Br(2) in
      the presence of BSA exhibit a single break at a lower surfactant concentration
      termed as C(1) (concentration corresponding to saturation of the interface)
      compared to their critical micelle concentration (CMC) in the buffered solution.
      However, for Brij58, CTAB+Brij58, and C(16)C(4)C(16)Br(2)+Brij58, two breaks were
      observed, first at the critical aggregation concentration (CAC), corresponding to
      onset of interaction with BSA and the second at C(1) corresponding to saturation
      of the interface. The interaction of CTAB+Brij58 and C(16)C(4)C(16)Br(2)+Brij58
      mixtures with the BSA solution is discussed in terms of competition between
      surfactant-surfactant and surfactant-BSA interactions. CTAB+Brij58 and
      C(16)C(4)C(16)Br(2)+Brij58 mixtures show nonideality with respect to mixed
      micelle formation, which is reflected in their interaction with the BSA. The
      interaction of CTAB+Brij58 with BSA decreases with increase in the mole fraction
      of CTAB in the mixture, whereas in C(16)C(4)C(16)Br(2)+Brij58 the reverse is the
      case. The results of the present study may prove fruitful in optimizing the
      properties of surfactant-protein mixtures relevant for many formulations.

PMID- 20148531
TI  - A concise enantioselective synthesis of (-)-ranirestat.
AB  - A concise, enantioselective synthesis of the potent aldose reductase inhibitor
      ranirestat (1) is reported. The synthesis was accomplished employing inexpensive,
      commercially available starting materials. A palladium-catalyzed asymmetric
      allylic alkylation (Pd-AAA) of malonate 4 was utilized as a key transformation to
      construct the tetrasubstituted chiral center in the target.

PMID- 20148533
TI  - Enhancement of hydrophobic interactions and hydrogen bond strength by
      cooperativity: synthesis, modeling, and molecular dynamics simulations of a
      congeneric series of thrombin inhibitors.
AB  - Accurately predicting the binding affinity of ligands to their receptors by
      computational methods is one of the major challenges in structure-based drug
      design. One of the potentially significant errors in these predictions is the
      common assumption that the ligand binding affinity contributions of noncovalent
      interactions are additive. Herein we present data obtained from two separate
      series of thrombin inhibitors containing hydrophobic side chains of increasing
      size that bind in the S3 pocket and with, or without, an adjacent amine that
      engages in a hydrogen bond with Gly 216. The first series of inhibitors has a m
      chlorobenzyl moiety binding in the S1 pocket, and the second has a benzamidine
      moiety. When the adjacent hydrogen bond is present, the enhanced binding affinity
      per A(2) of hydrophobic contact surface in the S3 pocket improves by 75% and 59%,
      respectively, over the inhibitors lacking this hydrogen bond. This improvement of
      the binding affinity per A(2) demonstrates cooperativity between the hydrophobic
      interaction and the hydrogen bond.

PMID- 20148532
TI  - Immunosuppressant neurotoxicity in rat brain models: oxidative stress and
      cellular metabolism.
AB  - Coadministration of the calcineurin inhibitor cyclosporine (CsA) and the mTOR
      inhibitors sirolimus (SRL) or everolimus (RAD) increases the efficacy of
      immunosuppression after organ transplantation. Neurotoxicity of CsA is a major
      clinical problem. Our goal was to assess the effects of CsA, SRL, and RAD on
      brain cell metabolism. The studies included the comparison of immunosuppressant
      mediated effects on glucose metabolism, energy production, and reactive oxygen
      species (ROS) formation in perfused rat brain slices, primary rat astrocytes, and
      C6 glioma cells. In brain slices and astrocytes, CsA inhibited Krebs cycle
      metabolism, while activating anaerobic glycolysis, most likely to compensate for
      the inhibition of mitochondrial energy production. SRL and RAD inhibited
      cytosolic glycolysis but did not cause changes in mitochondrial energy
      production. CsA + SRL inhibited Krebs cycle and glycolysis, thus reducing the
      ability of the cell to compensate for the negative effects of CsA on
      mitochondrial nucleoside triphosphate synthesis. In contrast to SRL at the
      concentrations tested, RAD reduced the CsA-induced ROS formation and antagonized
      CsA-induced effects on glucose and energy metabolism. Surprisingly, in C6 cells,
      SRL and RAD exposure resulted in high ROS concentrations without significant
      impairment of cell metabolism. Our results suggested that SRL enhances CsA
      induced ROS formation and negative metabolic effects in brain cells, while RAD
      seems to antagonize the CsA effects. However, the three models showed different
      metabolic responses when challenged with the study drugs. In contrast to SRL, RAD
      enhances ROS formation in C6 glioma cells but has only minor effects on normal
      rat brain tissue.

PMID- 20148534
TI  - Study of 2-H-heptafluoropropane and its thermal decomposition using UV
      photoelectron spectroscopy and ab initio molecular orbital calculations.
AB  - The thermal decomposition of 2-H-heptafluoropropane, CF(3)CHFCF(3), at low
      pressure, heavily diluted in argon, has been studied over the temperature range
      600-2000 degrees C using photoelectron spectroscopy. Comparison of the results
      obtained has been made with results of recent electronic structure calculations
      of possible decomposition pathways and results of a shock tube study. The most
      favored reaction thermodynamically, to produce CF(3)CF=CF(2) + HF, is found to be
      the main decomposition reaction at lower temperatures, 600-900 degrees C. At
      higher temperatures, 900-1200 degrees C, the decomposition reaction to give
      C(2)F(4) + CF(3)H was found to become important. No evidence for CF(3)CHFCF(3) -
      > CF(3)CHF + CF(3), a reaction expected to be important from a shock tube study,
      performed at much higher pressures, or for CF(3)CHFCF(3) --> CF(3)CF + CF(3)H was
      obtained, although for the latter reaction it is likely that CF(3)CF converts
      into C(2)F(4) under the conditions used before photoionization, in the ionization
      region of the photoelectron spectrometer. At higher temperatures C(3)F(6)
      decomposes to C(2)F(4) + CF(2), and C(2)F(4) decomposes to CF(2). Ab initio
      calculations have been performed of the adiabatic and vertical ionization
      energies of possible primary pyrolysis products to assist assignment of the
      photoelectron spectra recorded for heated flowing gas samples. A comparison is
      made between the threshold photoelectron spectrum and the photoelectron spectrum
      of CF(3)CF=CF(2).

PMID- 20148535
TI  - Helmholtz free energy of a phase containing a sparse ensemble of heterophase
      clusters with application to nucleation theory.
AB  - A decomposition of the Helmholtz free energy of a phase containing a sparse
      ensemble of heterophase clusters is derived based on classical statistical
      mechanics and on the general physical characteristics of such systems. It is not
      assumed that the phase is an ideal gas. The building blocks of this decomposition
      are the Helmholtz free energies of the constituents (phase and stationary
      heterophase clusters) and, for every cluster species, a volume V(k)(cm), which is
      of the magnitude of the thermal fluctuation volume of the center of mass of the
      stationary cluster containing k monomers. A definition of V(k)(cm) is given in
      terms of the configuration integrals of the clusters. V(k)(cm) is evaluated for k
      >> 1, with the result that V(k)(cm) is proportional to k(-1/2) and is a function
      of temperature, the specific volume, and the isothermal compressibility of the
      phase in the cluster. A thermodynamically consistent expression for the work to
      form a stationary cluster, which reads as Delta g(k)/(k(B)T) = -ak + (3/2)bk(2/3)
      + 3ck(1/3) + d, is derived. The coefficients a, b, c, and d depend on the
      thermodynamic properties of the homogeneous phases, on the surface tension, and
      on one additional phenomenological material function of temperature and pressure.
      The description is general and covers a wide class of materials. It is shown that
      the heterogeneous system represents the thermodynamic equilibrium and not the
      pure phase without clusters. The resulting expression for the equilibrium
      particle number, which is different from the one used in classical nucleation
      theory, is by a standard procedure input for the calculation of the stationary
      Becker-Doring nucleation rate and entails a correction factor for the classical
      nucleation rate. Comparison with experiments is provided for nucleation onset
      measurements of argon and for measurements of the homogeneous nucleation rate of
      water. Measurements and theory can be brought to match within the limits of
      experimental precision in both cases.

PMID- 20148536
TI  - Detection of subtle dynamical changes induced by unresolved "conformational
      coordinates" in single-molecule trajectories via goodness-of-fit tests.
AB  - Single-molecule experiments are allowing researchers to track the evolution of a
      few order parameters characterizing complex biomolecules. At fine temporal
      resolution, artifacts of unresolved degrees of freedom, for example, those
      induced by collective molecular motion, often influence the dynamics. Reliably
      detecting subtle changes in dynamics at the nanoscale can be difficult due to the
      inherent stochasticity, but such changes can have relevance to understanding
      complex enzyme kinetics. Surrogate models can be used to summarize the
      information content in single-molecule time series (containing fluctuations
      occurring over multiple time scales). The focus in this article is on detecting
      slow time scale changes through the use of the surrogates. The conditional
      density, associated with the surrogates, allows one to formulate quantitative
      hypothesis tests which can detect the influence of unresolved coordinates in
      cases where the dynamics are modulated subtly. The relevance of quantitative (and
      appropriate) testing methods to analyze single-molecule time series is discussed
      and demonstrated. A brief discussion on some merits of using frequentist (versus
      Bayesian) time series methods to analyze single-molecule data is also presented.
      Idealized simulations mimicking features relevant to some enzyme systems where an
      "unresolved conformational coordinate" slowly evolves (1) with inertia and (2)
      diffusively are studied in the nonstationary (nonergodic) setting; however, the
      findings are also relevant to experimentally measured time series and stationary
      signals.

PMID- 20148537
TI  - Resveratrol, genistein, and curcumin bind bovine serum albumin.
AB  - We report the complexation of bovine serum albumin (BSA) with resveratrol,
      genistein, and curcumin, at physiological conditions, using constant protein
      concentration and various polyphenol contents. FTIR, CD, and fluorescence
      spectroscopic methods were used to analyze the ligand binding mode, the binding
      constant, and the effects of complexation on BSA stability and conformation.
      Structural analysis showed that polyphenols bind BSA via hydrophilic and
      hydrophobic interactions with the number of bound polyphenol (n) being 1.30 for
      resveratrol-BSA, 1.30 for genistein-BSA, and 1.0 for curcumin-BSA. The polyphenol
      BSA binding constants were K(Res-BSA) = 2.52(+/-0.5) x 10(4) M(-1), K(Gen-BSA) =
      1.26(+/-0.3) x 10(4) M(-1), and K(Cur-BSA) = 3.33(+/-0.8) x 10(4) M(-1).
      Polyphenol binding altered BSA conformation with a major reduction of alpha-helix
      and an increase in beta-sheet and turn structures, indicating a partial protein
      unfolding.

PMID- 20148539
TI  - Cobalt-catalyzed cross-coupling reactions.

PMID- 20148538
TI  - Layer-by-layer assembled polyampholyte microgel films for simultaneous release of
      anionic and cationic molecules.
AB  - A facile layer-by-layer (LbL) assembly method for the fabrication of matrix films
      capable of coloading and simultaneous release of oppositely charged molecules has
      been established by using polyampholyte microgels as building blocks.
      Polyampholyte microgels (named PAH-D-CO(2)) containing amine and carbamate groups
      were LbL assembled with polyanion poly(sodium 4-styrenesulfonate) (PSS) to
      produce PAH-D-CO(2)/PSS multilayer films. The successful fabrication of PAH-D
      CO(2)/PSS multilayer films was verified by quartz crystal microbalance
      measurements and cross-sectional scanning electron microscopy. Anionic methyl
      orange and cationic rhodamine 6G were coloaded into PAH-D-CO(2)/PSS multilayer
      films because of the electrostatic interaction of these dyes with amine and
      carbamate groups in the PAH-D-CO(2)/PSS microgel films. The abundance of amine
      and carbamate groups as well as the swelling capacity of PAH-D-CO(2) microgels
      guarantees the high loading capacity of the PAH-D-CO(2)/PSS multilayer films
      toward the anionic and cationic dyes. Methyl orange and rhodamine 6G were
      simultaneously released from PAH-D-CO(2)/PSS multilayer films when immersing the
      dye-loaded films into 0.9% normal saline. The releasing behaviors of the
      polyampholyte microgel films can be tailored by capping the PAH-D-CO(2)/PSS films
      with barrier layers. The polyampholyte microgel films of PAH-D-CO(2)/PSS are
      expected to be widely useful as matrixes for coloading oppositely charged
      functional guest materials such as drugs and even for their controlled release.

PMID- 20148540
TI  - Hot water from cold. The dissociative recombination of water cluster ions.
AB  - Dissociative recombination of the Zundel cation D(5)O(2)(+) almost exclusively
      produces D + 2 D(2)O with a maximum kinetic energy release of 5.1 eV. An imaging
      technique is used to investigate the distribution of the available reaction
      energy among these products. Analysis shows that as much as 4 eV can be stored
      internally by the molecular fragments, with a preference for producing highly
      excited molecular fragments, and that the deuteron shows a nonrandom distribution
      of kinetic energies. A possible mechanism and the implications for these
      observations are addressed.

PMID- 20148541
TI  - Catechol-grafted poly(ethylene glycol) for PEGylation on versatile substrates.
AB  - We report on catechol-grafted poly(ethylene) glycol (PEG-g-catechol) for the
      preparation of nonfouling surfaces on versatile substrates including adhesion
      resistant PTFE. PEG-g-catechol was prepared by the step-growth polymerization of
      PEO to which dopamine, a mussel-derived adhesive molecule, was conjugated. The
      immersion of substrates into an aqueous solution of PEG-g-catechol resulted in
      robust PEGylation on versatile surfaces of noble metals, oxides, and synthetic
      polymers. Surface PEGylation was unambiguously confirmed by various surface
      analytical tools such as ellipsometry, goniometry, infrared spectroscopy, and X
      ray photoelectron spectroscopy. Contrary to existing PEG derivatives that are
      difficult-to-modify synthetic polymer surfaces, PEG-g-catechol can be considered
      to be a new class of PEGs for the facile surface PEGylation of various types of
      surfaces.

PMID- 20148542
TI  - Luminescence, singlet oxygen production, and optical power limiting of some
      diacetylide platinum(II) diphosphine complexes.
AB  - A series of four new trans-diphosphine Pt(II) diacetylide complexes, with a
      thiophene and two benzenoid rings in each acetylide ligand, have been synthesized
      and characterized with respect to optical absorption, spectrally and time
      resolved luminescence, and optically nonlinear properties such as two-photon
      absorption cross section and optical power limiting. Density functional theory
      (DFT) calculations of a few ground state conformations of three Pt(II)
      diacetylide structures showed similar total energy for each geometry-optimized
      rotamer but some differences in the vertical excitation energies and in the
      ligand-to-metal charge-transfer character. The wavelengths of the calculated
      excitations were found to be red-shifted compared with peaks in the optical
      absorption spectra, but the general trends and shifts of wavelengths between the
      different structures are well reproduced. Static emission spectra for degassed
      samples in THF solution of the larger compounds showed small Stokes shifts and
      low fluorescence quantum yields, indicating fast intersystem crossing to the
      triplet manifold. More pronounced differences between the compounds were
      displayed in the phosphorescence data, in terms of spectral emission wavelengths
      and decay times. For instance, the phosphorescence decay of the compound with the
      thiophene ring close to the Pt center was found to be significantly faster than
      for the other compounds. A possible relationship between triplet lifetime and
      conformation of the compounds is discussed. It was also demonstrated that the
      quenching of the excited triplet states in air-saturated samples involves energy
      transfer to the oxygen triplet state, and subsequent generation of singlet oxygen
      showing the typical emission at approximately 1275 nm. The amount of produced
      singlet oxygen followed the phosphorescence yields of the solute molecules. Two
      photon absorption cross sections (sigma(2)) were measured and showed values on
      the order of 10 GM at 780 nm for all compounds. Optical power limiting
      measurements of the new complexes in THF using 5 ns pulses, showed only slightly
      better performance at the wavelength of 532 nm compared to that of similar
      platinum compounds with only two aryl rings in each ligand. At 600 nm the
      complexes with three aryl rings were significantly better optical limiters than
      the smaller compounds with two aryl rings in the ligands.

PMID- 20148543
TI  - Confocal laser imaging and annealing of quantum-dot-coated silica colloidal
      crystals.
AB  - We demonstrate the ability to image, melt, and anneal repulsive electrostatic and
      attractive depletion colloidal crystals of quantum-dot-decorated SiO(2)
      microparticles (QDSs). QDS colloidal crystals showed increased thermal motion,
      melting, and convection only in the presence of CSLM imaging, which we attribute
      to quantum dot (QD) heating. We exploit this local heating effect to anneal a
      single defect-rich, polycrystalline domain. Our results demonstrate a method to
      anneal colloidal crystals locally with focused lasers and the role of heating
      when using many QD tags per particle in CSLM imaging.

PMID- 20148544
TI  - Properties of Ca-rich and Mg-rich carbonate films on dolomite: implications for
      compositional surface mapping with scanning force microscopy.
AB  - A self-limited monolayer grown on dolomite (CaMg(CO(3))(2)), showing distinct
      friction contrast with the substrate as reported earlier using lateral force
      microscopy, was investigated with in situ atomic force microscopy (AFM) adhesion
      mapping and force-modulation techniques. Force-modulation microscopy revealed
      lower stiffness on a Ca-rich film in comparison to that on the dolomite surface.
      The friction contrast therefore results from a larger tip-surface contact area
      when the AFM probe is in contact with the Ca-rich film as opposed to the contact
      area with dolomite. The Ca-rich film also exhibited a slightly higher adhesion
      than did the dolomite substrate; however, the critical shear stresses for the two
      tip-surface contacts were indistinguishable. A comparative study with a Mg-rich
      film did not yield noticeable force modulation contrast, indicating similar
      surface stiffness of the film and the dolomite surface. The similarity in these
      stiffness quantities was further corroborated by friction-load data that
      demonstrated similar friction forces on the two surfaces. The previously reported
      film strain in the Ca-rich system is likely linked to the lower stiffness
      observed, with both of these properties related to the Ca/Mg composition of the
      film.

PMID- 20148545
TI  - Theoretical studies of the structural, electronic, and optical properties of
      phosphafluorenes.
AB  - Phosphafluorenes have drawn increasing attention recently in the applications of
      organic electronic devices due to their particular optoelectronic properties. To
      reveal their molecular structures, optoelectronic properties, and structure
      property relationships of the newly emerged functional materials, an in-depth
      theoretical investigation was elaborated via quantum chemical calculations. The
      optimized geometric and electronic structures in both ground and exited states,
      the mobility of the hole and electron, the absorption and emission spectra, and
      the singlet exciton generation fraction of these novel phosphors-containing
      materials have been studied by density functional theory (DFT), single excitation
      configuration interaction (CIS), time-dependent density functional theory (TDDFT)
      methods, and the polarizable continuum model (PCM). The results show that the
      highest occupied molecular orbitals (HOMOs), the lowest unoccupied molecular
      orbitals (LUMOs), triplet energies ((3)E(g)), energy gaps (E(g)), as well as some
      other electronic properties including ionization potentials (IPs), electron
      affinities (EAs), reorganization energies (lambda), the singlet exciton
      generation fraction, radiative lifetime, and absorption and emission spectra can
      be easily tuned by chemical modifications of the phosphorus atom via methyl,
      phenyl, oxygen, sulfur, or selenium substitution, indicating that the
      phosphafluorenes are interesting optoelectronic functional materials, which have
      great potential in the applications of OLEDs, organic solar cells, organic
      storage, and sensors.

PMID- 20148546
TI  - Pluronic micelle shuttle between water and an ionic liquid.
AB  - We demonstrate an effective micelle shuttle between water and a hydrophobic ionic
      liquid and its application in transportation in the biphasic system, using a
      commercially available and inexpensive Pluronic block copolymer. The
      poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (P123) block copolymer
      self-assembles into micelles in both water and the ionic liquid, 1-butyl-3
      methylimidazolium hexafluorophosphate, as characterized by dynamic light
      scattering. The poly(ethylene oxide) blocks provide the well-solvated corona,
      whereas the poly(propylene oxide) blocks form the solvophobic core. The micelles
      can spontaneously transfer between the two phases upon a simple temperature
      stimulus; the transfer is reversible and repeatable, and (1)H NMR analysis
      indicates quantitative transfer. The micelle nanocarriers are used to transport
      various cargoes in the biphasic system: fully reversible transport of hydrophobic
      small organic dyes into and out of water and facile extraction of an ionic liquid
      phobic polymer from the ionic liquid. This simple round-trip delivery system may
      be used in delivery, separations, and extraction in synthesis and biphasic
      catalysis involving ionic liquids.

PMID- 20148547
TI  - Accelerated formation of THF-H2 clathrate hydrate in porous media.
AB  - Porous media were used to control the hydrogen clathrate particle size in order
      to accelerate its formation kinetics. Stoichiometric tetrahydrofuran-hydrogen
      binary clathrate hydrates with approximately 1 wt % hydrogen loading formed in
      the mesopores of four porous media with median pore diameters of 49, 65, 100, and
      226 A at 270 K and hydrogen pressure of 65 bar. The minimum formation time for
      the tetrahydrofuran-hydrogen binary clathrate hydrates was 27 min in a porous
      medium with a median pore diameter of 49 A, which is 6-22 times faster than the
      tetrahydrofuran-hydrogen binary clathrate hydrates formed in the bulk ice. The
      clathrate formation time was found to increase with pore size of the porous
      media. A modified shrinking core kinetic model was used to calculate the
      diffusivity of hydrogen in the tetrahydrofuran-hydrogen binary clathrate
      hydrates. Hydrogen diffusivities in the tetrahydrofuran-hydrogen binary clathrate
      hydrates were found to be on the order of 10(-18)-10(-19) m(2)/s and decrease
      with increasing pore size or clathrate particle size.

PMID- 20148549
TI  - A bright future for the Montreal Protocol.
AB  - Environmental policy of the 1980s could provide direction and solutions for 21st
      century debates.

PMID- 20148548
TI  - Gadolinium oxide ultranarrow nanorods as multimodal contrast agents for optical
      and magnetic resonance imaging.
AB  - We demonstrate a simple synthetic strategy for the fabrication of single-phase
      rare earth (RE) doped gadolinium oxide (Gd(2)O(3):RE where RE = terbium (Tb),
      ytterbium (Yb), and erbium (Er)) nanorods (NRs) as multimodal imaging probes. The
      NRs are ultranarrow and exhibit both emission and magnetic characteristics. The
      Tb-doped and Yb/Er-codoped Gd(2)O(3) NRs exhibit down- and up-conversion
      fluorescence respectively, and also exhibit paramagnetism. Importantly, these
      codoped NRs possess excellent magnetic characteristics, as shown in their
      longitudinal relaxation time (T1) -weighted image contrast, which is closer to
      that of commercial Gadovist for magnetic resonance imaging (MRI) applications.
      This property opens up new avenues in the development of contrast agents.

PMID- 20148550
TI  - Performance of a high flow rate, thermally extractable multicapillary denuder for
      atmospheric semivolatile organic compound concentration measurement.
AB  - A high flow rate (300 L min(-1)) multicapillary denuder was designed to collect
      trace atmospheric semivolatile organic compounds (SOCs). The denuder is coated
      with a reusable, polydimethylsiloxane stationary phase as a nonselective
      absorbent for SOCs. A solvent-free thermal desorption method was developed,
      including sample cleanup, that is selective for nonpolar SOCs, and has low
      consumables cost per sample. The entire sample is transferred into the gas
      chromatograph to minimize the sampling time required to collect detectable
      analyte mass. Trace concentrations (0.1-100 pg m(-3)) of polychlorinated
      biphenyls and hexachlorobenzene were measured in the atmosphere near Lake
      Superior in sample times of 3.2-6.2 h. Overall method precision was determined
      using field duplicates and compared to the conventional high-volume sampler
      method. Method precision (coefficient of variation) of 16% was found for the high
      flow denuder compared to 21% for the high-volume method. The relative difference
      between the two methods was 25%, with the high-flow denuder method giving
      generally lower concentrations. The high-flow denuder is an alternative to high
      volume or passive samplers when it is desirable to separate gaseous from particle
      associated SOCs upstream of a filter. The method is advantageous for studies that
      require high temporal resolution.

PMID- 20148551
TI  - Arsenic effects and behavior in association with the Fe(II)-catalyzed
      transformation of schwertmannite.
AB  - In acid-mine drainage and acid-sulfate soil environments, the cycling of Fe and
      As are often linked to the formation and fate of schwertmannite (Fe(8)O(8)(OH)(8
      2x)(SO(4))(x)). When schwertmannite-rich material is subjected to near-neutral
      Fe(III)-reducing conditions (e.g., in reflooded acid-sulfate soils or mining-lake
      sediments), the resulting Fe(II) can catalyze transformation of schwertmannite to
      goethite. This work examines the effects of arsenic(V) and arsenic(III) on the
      Fe(II)-catalyzed transformation of schwertmannite and investigates the associated
      consequences of this mineral transformation for arsenic mobilization. A series of
      9-day anoxic transformation experiments were conducted with synthetic
      schwertmannite and various additions of Fe(II), As(III), and As(V). X-ray
      diffraction (XRD) and Fe K-edge extended X-ray absorption fine structure (EXAFS)
      spectroscopy demonstrated that, in the absence of Fe(II), schwertmannite
      persisted as the dominant mineral phase. Under arsenic-free conditions, 10 mM
      Fe(II) catalyzed rapid and complete transformation of schwertmannite to goethite.
      However, the magnitude of Fe(II)-catalyzed transformation decreased to 72% in the
      presence of 1 mM As(III) and to only 6% in the presence of 1 mM As(V). This
      partial Fe(II)-catalyzed transformation of As(III)-sorbed schwertmannite did not
      cause considerable As(III) desorption. In contrast, the formation of goethite via
      partial transformation of As(III)- and As(V)-sorbed schwertmannite significantly
      decreased arsenic mobilization under Fe(III)-reducing conditions. This implies
      that the Fe(II)-catalyzed transformation of schwertmannite to goethite may help
      to stabilize solid-phase arsenic and retard its subsequent release to
      groundwater.

PMID- 20148552
TI  - Contact geometry symmetry dependence of field effect gating in single-molecule
      transistors.
AB  - The geometric aspects for the functionality of a molecule-based field effect
      transistor (FET) are analyzed. A computational study is performed on molecular
      models involving a well-defined conjugation plane coupled to gold-based
      electrodes through thiol bonding. Transport gating of the FET is shown to depend
      on a symmetry-breaking effect induced by the gating field. This effect is also
      related to the orientation of the field relative to the gold-thiol bonds, the
      molecular conjugation plane, and the overall symmetry of the device. First, it is
      found that the presence of a center of inversion in the bulk-coupled molecular
      system results in the cancellation of the transisting response. Second, a mirror
      plane of the molecule-bulk system, which includes the transport vector, will
      cancel the gating response to fields oriented perpendicular to that mirror plane.
      The symmetry properties are determined for the bulk contacted molecular junction.

PMID- 20148553
TI  - Comprehensive and cost-effective NMR spectroscopy of methyl groups in large
      proteins.
AB  - An NMR approach is described which yields the methyl resonance assignments of
      alanine, threonine, valine, leucine, and isoleucine residues in proteins with
      high sensitivity and excellent resolution. The method relies on protein samples
      produced by bacterial expression using [(1)H,(13)C]-D-glucose and approximately
      100% D(2)O, which is cost-effective and ensures the isotopic enrichment of all
      possible methyl groups. Magnetization transfer throughout the methyl-containing
      side chains is possible with this labeling scheme due to the high level of
      deuteration along the amino acid side chain, coupled with the selection of the
      favorable CHD(2) methyl isotopomer for detection. In an application to the 34 kDa
      periplasmic binding protein FepB 164 out of 195 methyl groups (85%) were assigned
      sequence-specifically and stereospecifically. This percentage increases to 91%
      when taking into account that not all backbone assignments are available for this
      system. The remaining unassigned methyl groups belong to six leucine residues,
      caused by low cross-peak intensities, and four alanine residues due to degeneracy
      of the (13)C(alpha)/(13)C(beta) frequencies. Our results demonstrate that NMR
      spectroscopic investigations of protein structure, dynamics, and interactions can
      be extended to include all methyl-containing amino acids also for larger
      proteins.

PMID- 20148554
TI  - Doubly deuterium-labeled patchouli alcohol from cyclization of singly labeled [2
      (2)H(1)]farnesyl diphosphate catalyzed by recombinant patchoulol synthase.
AB  - Incubations of isotopically pure [2-(2)H(1)](E,E)-farnesyl diphosphate with
      recombinant patchoulol synthase (PTS) from Pogostemon cablin afforded a 65:35
      mixture of monodeuterated and dideuterated patchoulols as well as numerous
      sesquiterpene hydrocarbons. Extensive NMR analyses ((1)H and (13)C NMR, (1)H
      homodecoupling NMR, HMQC, and (2)H NMR) of the labeled patchoulol mixture and
      comparisons of the spectra with those of unlabeled alcohol led to the conclusion
      that the deuterium label was located at positions (patchoulol numbering system)
      C5 (both isotopomers, ca. 100%) and C12 (minor isotopomer, 30-35%), that is, an
      approximately 2:1 mixture of [5-(2)H(1)]- and [5,12-(2)H(2)]-patchoulols. Low
      resolution FIMS analyses and isotope ratio calculations further corroborated the
      composition of the mixture as mainly one singly deuterated and one doubly
      deuterated patchoulol. From a mechanistic point of view, the formation of [5,12
      (2)H(2)]patchoulol is rationalized through the intermediacy of an unknown
      exocyclic [7,10:1,5]patchoul-4(12)-ene (15-d(1)), which could incorporate a
      deuteron at the C-12 position on the pathway to doubly labeled patchoulol. The
      corresponding depletion of deuterium content observed in the hydrocarbon
      coproducts, beta-patchoulene and alpha-guaiene (55% d(0)), identified the source
      of the excess label found in patchoulol-d(2). Comparison of the PTS amino acid
      sequence with those of other sesquiterpene synthases, and examination of an
      active site model, suggested that re-orientation of leucine 410 side chain in PTS
      might facilitate the creation of a 2-pocket active site where the observed
      deuteron transfers could occur. The retention of deuterium at C5 in the labeled
      patchoulol and its absence at C4 rule out an alternative mechanism involving two
      consecutive 1,2-hydride shifts and appears to confirm the previously proposed
      occurrence of a 1,3-hydride shift across the 5-membered ring. A new,
      semisystematic nomenclature is presented for the purpose of distinguishing the
      three different skeletal structures of the patchoulane sesquiterpenes.

PMID- 20148555
TI  - RNA conformation in catalytically active human telomerase.
AB  - We have used single-molecule fluorescence microscopy to study the folded state of
      human telomerase RNA (hTR). Here we show that hTR adopts a new conformation on
      binding to human telomerase reverse transcriptase (hTERT) and reconstitution of
      an active ribonucleoprotein complex. Our data are consistent with the formation
      of an RNA pseudoknot in active human telomerase.

PMID- 20148556
TI  - Synthesis and structure-activity correlation of natural-product inspired
      cyclodepsipeptides stabilizing F-actin.
AB  - The fundamental role played by actin in the regulation of eukaryotic cell
      maintenance and motility renders it a primary target for small-molecule
      intervention. In this arena, a class of potent cytotoxic cyclodepsipeptide
      natural products has emerged over the last quarter-century to stimulate the
      fields of biology and chemistry with their unique actin-stabilizing properties
      and complex peptide-polyketide hybrid structures. Despite considerable research
      effort, a structural basis for the activity of these secondary metabolites
      remains elusive, not least for the lack of high-resolution structural data and a
      reliable synthetic route to diverse compound libraries. In response to this, an
      efficient solid-phase approach has been developed and successfully applied to the
      total synthesis of jasplakinolide and chondramide C and diverse analogues. The
      key macrocylization step was realized using ruthenium-catalyzed ring-closing
      metathesis (RCM) that in the course of a library synthesis produced discernible
      trends in metathesis reactivity and E/Z-selectivity. After optimization, the RCM
      step could be operated under mild conditions, a result that promises to
      facilitate the synthesis of more extensive analogue libraries for structure
      function studies. The growth inhibitory effects of the synthesized compounds were
      quantified and structure-activity correlations established which appear to be in
      good alignment with relevant biological data from natural products. In this way a
      number of potent unnatural and simplified analogues have been found. Furthermore,
      potentially important stereochemical and structural components of a common
      pharmacophore have been identified and rationalized using molecular modeling.
      These data will guide in-depth mode-of-action studies, especially into the
      relationship between the cytotoxicity of these compounds and their actin
      perturbing properties, and should inform the future design of simplified and
      functionalized actin stabilizers as well.

PMID- 20148557
TI  - Palladium-catalyzed intermolecular aminofluorination of styrenes.
AB  - A novel palladium-catalyzed intermolecular aminofluorination of styrenes, with N
      fluorobenzenesulfonimide (NFSI) functioning not only as a fluorinating reagent
      but also as an aminating reagent, has been developed. The reaction afforded
      vicinal fluoroamine products with very high regioselectivity. This transformation
      may involve fluoropalladation of styrene as a key step for C-F bond formation.
      The bidental nitrogen ligand is crucial to achieving the transformation
      successfully.

PMID- 20148558
TI  - Evolution of catalysts directed by genetic algorithms in a plug-based
      microfluidic device tested with oxidation of methane by oxygen.
AB  - This paper uses microfluidics to implement genetic algorithms (GA) to discover
      new homogeneous catalysts using the oxidation of methane by molecular oxygen as a
      model system. The parameters of the GA were the catalyst, a cocatalyst capable of
      using molecular oxygen as the terminal oxidant, and ligands that could tune the
      catalytic system. The GA required running hundreds of reactions to discover and
      optimize catalyst systems of high fitness, and microfluidics enabled these
      numerous reactions to be run in parallel. The small scale and volumes of
      microfluidics offer significant safety benefits. The microfluidic system included
      methods to form diverse arrays of plugs containing catalysts, introduce gaseous
      reagents at high pressure, run reactions in parallel, and detect catalyst
      activity using an in situ indicator system. Platinum(II) was identified as an
      active catalyst, and iron(II) and the polyoxometalate H(5)PMo(10)V(2)O(40) (POM
      V2) were identified as active cocatalysts. The Pt/Fe system was further optimized
      and characterized using NMR experiments. After optimization, turnover numbers of
      approximately 50 were achieved with approximately equal production of methanol
      and formic acid. The Pt/Fe system demonstrated the compatibility of iron with the
      entire catalytic cycle. This approach of GA-guided evolution has the potential to
      accelerate discovery in catalysis and other areas where exploration of chemical
      space is essential, including optimization of materials for hydrogen storage and
      CO(2) capture and modifications.

PMID- 20148559
TI  - Quantum mechanical/molecular mechanical modeling finds Diels-Alder reactions are
      accelerated less on the surface of water than in water.
AB  - Quantum and molecular mechanics calculations for the Diels-Alder reactions of
      cyclopentadiene with 1,4-naphthoquinone, methyl vinyl ketone, and acrylonitrile
      have been carried out at the vacuum-water interface and in the gas phase. In
      conjunction with previous studies of these cycloadditions in dilute solution, a
      more complete picture of aqueous environmental effects emerges with implications
      for the origin of observed rate accelerations using heterogeneous aqueous
      suspensions, "on water" conditions. The pure TIP4P water slab maintains the bulk
      density and hydrogen-bonding properties in central water layers. The bulk region
      merges to vacuum over a ca. 5 A band with progressive diminution of the density
      and hydrogen bonding. The relative free energies of activation and transition
      structures for the reactions at the interface are found to be intermediate
      between those calculated in the gas phase and in bulk water; i.e., for the
      reaction with 1,4-naphthoquinone, the DeltaDeltaG(++) values relative to the gas
      phase are -3.6 and -7.3 kcal/mol at the interface and in bulk water,
      respectively. Thus, the results do not support the notion that a water surface is
      more effective than bulk water for catalysis of such pericyclic reactions. The
      trend is in qualitative agreement with expectations based on density
      considerations and estimates of experimental rate constants for the gas phase, a
      heterogeneous aqueous suspension, and a dilute aqueous solution for the reaction
      of cyclopentadiene with methyl vinyl ketone. Computed energy pair distributions
      reveal a uniform loss of 0.5-1.0 hydrogen bond for the reactants and transition
      states in progressing from bulk water to the vacuum-water interface.
      Orientational effects are apparent at the surface; e.g., the carbonyl group in
      the methyl vinyl ketone transition structure is preferentially oriented into the
      surface. Also, the transition structure for the 1,4-naphthoquinone case is buried
      more in the surface, and the free energy of activation for this reaction is most
      similar to the result in bulk water.

PMID- 20148560
TI  - Comparative analysis of small molecules and histone substrate analogues as LSD1
      lysine demethylase inhibitors.
AB  - LSD1 is a flavin-dependent histone demethylase that oxidatively removes methyl
      groups from Lys-4 of histone H3. LSD1 belongs to the amine oxidase enzyme
      superfamily which utilize molecular oxygen to transform amines to imines that are
      hydrolytically cleaved to formaldehyde. In prior studies, it has been shown that
      monoamine oxidase inhibitory scaffolds such as propargylamines and
      cyclopropylamines can serve as mechanism-based inactivators of LSD1.
      Propargylamine-histone H3 peptide analogues are potent LSD1 inhibitors, whereas
      small molecule antidepressant MAO acetylenic inhibitors like pargyline do not
      inhibit LSD1. In contrast, the small molecule MAO cyclopropylamine inhibitor
      tranylcypromine is a time-dependent LSD1 inhibitor but exo-cyclopropylamine
      peptide substrate analogue is not. To provide further insight into small molecule
      versus peptide relationships in LSD1 inhibition, herein we further our analysis
      of warheads in peptide scaffolds to include the chlorovinyl, endo
      cyclopropylamine, and hydrazine-functionalities as LSD1 inactivators. We find
      that chlorovinyl-H3 is a mechanism-based LSD1 inactivator whereas endo
      cyclopropylamine-H3 does not show time-dependent inactivation. The hydrazine-H3
      was shown to be the most potent LSD1 suicide inhibitor yet reported, more than 20
      fold more efficient in inhibiting demethylation than propargylamine-H3
      derivatives. We re-explored MAO antidepressant agent phenelzine
      (phenethylhydrazine), previously reported to be a weak LSD1 inhibitor, and found
      that it is far more potent than previously appreciated. We show that phenelzine
      can block histone H3K4Me demethylation in cells, validating it as a pharmacologic
      tool and potential lead structure for anticancer therapy.

PMID- 20148561
TI  - Enantioselective conjugate silyl additions to cyclic and acyclic unsaturated
      carbonyls catalyzed by Cu complexes of chiral N-heterocyclic carbenes.
AB  - An efficient Cu-catalyzed protocol for enantioselective addition of a
      dimethylphenylsilanyl group to a wide range of cyclic and acyclic unsaturated
      ketones, esters, acrylonitriles, and alpha,beta,gamma,delta-dienones is
      disclosed. Reactions are performed in the presence of 1-2 mol % of commercially
      available and inexpensive CuCl, a readily accessible monodentate imidazolinium
      salt, and commercially available (dimethylphenylsilyl)pinacolatoboron. Cu
      catalyzed enantioselective conjugate additions proceed to completion within only
      2 h to afford the desired silanes in 87-97% yield and 90:10-99:1 enantiomeric
      ratio (er). Use of a proton source (e.g., MeOH) is not required; accordingly,
      synthetically versatile alpha-silyl boron enolates can be obtained. The special
      utility of the present protocol, in comparison with the related catalytic
      enantioselective aldol and boronate conjugate additions, is discussed and
      illustrated through various functionalizations of the enantiomerically enriched
      beta-silylcarbonyls.

PMID- 20148562
TI  - 5-Amino-2-aroylquinolines as highly potent tubulin polymerization inhibitors.
AB  - A series of aroylquinoline derivatives were synthesized and evaluated for
      anticancer activity. 5-Amino-6-methoxy-2-aroylquinoline 15 showed more potent
      antiproliferative activity (IC(50) values ranging from 0.2 to 0.4 nM) as compared
      to 1a (combretastatin A-4) (IC(50) = 1.9-835 nM) against various human cancer
      cell lines and a MDR-resistant cancer cell line. Compound 15 (IC(50) = 1.6
      microM) exhibited more potent inhibition of tubulin polymerization than 1a
      (IC(50) = 2.1 microM) and showed strong binding property to the colchicine
      binding site of microtubules.

PMID- 20148563
TI  - BRAF inhibitors based on an imidazo[4,5]pyridin-2-one scaffold and a meta
      substituted middle ring.
AB  - We recently reported on the development of a novel series of BRAF inhibitors
      based on a tripartite A-B-C system characterized by a para-substituted central
      aromatic core connected to an imidazo[4,5]pyridin-2-one scaffold and a
      substituted urea linker. Here, we present a new series of BRAF inhibitors in
      which the central phenyl ring connects to the hinge binder and substrate pocket
      of BRAF with a meta-substitution pattern. The optimization of this new scaffold
      led to the development of low-nanomolar inhibitors that permits the use of a
      wider range of linkers and terminal C rings while enhancing the selectivity for
      the BRAF enzyme in comparison to the para series.

PMID- 20148564
TI  - Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based
      on a biphenyl template.
AB  - Single agents against multiple drug targets are of increasing interest. Hormone
      dependent breast cancer (HDBC) may be more effectively treated by dual inhibition
      of aromatase and steroid sulfatase (STS). The aromatase inhibitory pharmacophore
      was thus introduced into a known biphenyl STS inhibitor to give a series of novel
      dual aromatase-sulfatase inhibitors (DASIs). Several compounds are good aromatase
      or STS inhibitors and DASI 20 (IC(50): aromatase, 2.0 nM; STS, 35 nM) and its
      chlorinated congener 23 (IC(50): aromatase, 0.5 nM; STS, 5.5 nM) are examples
      that show exceptional dual potency in JEG-3 cells. Both biphenyls share a para
      sulfamate-containing ring B and a ring A, which contains a triazol-1-ylmethyl
      meta to the biphenyl bridge and para to a nitrile. At 1 mg/kg po, 20 and 23
      reduced plasma estradiol levels strongly and inhibited liver STS activity
      potently in vivo. 23 is nonestrogenic and potently inhibits carbonic anhydrase II
      (IC(50) 86 nM). A complex was crystallized and its structure was solved by X-ray
      crystallography. This class of DASI should encourage further development toward
      multitargeted therapeutic intervention in HDBC.

PMID- 20148566
TI  - Rhodium-germanium carbonyl complexes.
AB  - The compound Rh(CO)(4)GePh(3), 3, was obtained in a high yield (95%) from the
      reaction of [Rh(CO)(2)Cl](2) with LiGePh(3) under a CO atmosphere. Reaction of 3
      with HGePh(3) yielded the new dirhodium compound Rh(2)(CO)(6)(GePh(3))(2)(mu
      GePh(2)), 4 (55% yield), by a loss of CO and the combination of one equivalent of
      HGePh(3) with two equivalents of 3. Compound 4 contains contains a Rh-Rh bond and
      a bridging GePh(2) ligand formed by cleavage of a phenyl group from a GePh(3)
      ligand. Compound 4 reacts with Pt(PBu(t)(3))(2) to add a Pt(PBu(t)(3)) to the Rh
      Rh bond to form the compound PtRh(2)(CO)(6)(GePh(3))(2)(PBu(t)(3))(mu-GePh(2)), 5
      (42% yield). Fenske-Hall molecular orbitals were calculated for compounds 4 and 5
      to explain the nature of the metal-metal bonding in these compounds. Compounds 3
      5 were fully characterized by IR, NMR, and single-crystal X-ray diffraction
      analyses.

PMID- 20148565
TI  - Antitumor agents. 272. Structure-activity relationships and in vivo selective
      anti-breast cancer activity of novel neo-tanshinlactone analogues.
AB  - Neo-tanshinlactone (1) and its previously reported analogues, such as 2, are
      potent and selective in vitro antibreast cancer agents. The synthetic pathway to
      2 was optimized from seven to five steps, with a better overall yield. Structure
      activity relationships studies on these compounds revealed some key molecular
      determinants for this family of antibreast agents. Several derivatives (19-21 and
      24) exerted potent and selective antibreast cancer activity with IC(50) values of
      0.3, 0.2, 0.1, and 0.1 microg/mL, respectively, against the ZR-75-1 cell lines.
      Compound 24 was 2- to 3-fold more potent than 1 against SK-BR-3 and ZR-75-1.
      Importantly, 21 exhibited high selectivity; it was 23 times more active against
      ZR-75-1 than MCF-7. Compound 20 had an approximately 12-fold ratio of SK-BR-3/MCF
      7 selectivity. In addition, analogue 2 showed potent activity against a ZR-75-1
      xenograft model, but not PC-3 and MDA-MB-231 xenografts, as well as high
      selectivity against breast cancer cell line compared with normal breast tissue
      derived cell lines. Further development of lead compounds 19-21 and 24 as
      clinical trial candidates is warranted.

PMID- 20148567
TI  - Double-sided CdS and CdSe quantum dot co-sensitized ZnO nanowire arrays for
      photoelectrochemical hydrogen generation.
AB  - We report the design and characterization of a novel double-sided CdS and CdSe
      quantum dot cosensitized ZnO nanowire arrayed photoanode for photoelectrochemical
      (PEC) hydrogen generation. The double-sided design represents a simple analogue
      of tandem cell structure, in which the dense ZnO nanowire arrays were grown on an
      indium-tin oxide substrate followed by respective sensitization of CdS and CdSe
      quantum dots on each side. As-fabricated photoanode exhibited strong absorption
      in nearly the entire visible spectrum up to 650 nm, with a high incident-photon
      to-current-conversion efficiency (IPCE) of approximately 45% at 0 V vs Ag/AgCl.
      On the basis on a single white light illumination of 100 mW/cm(2), the photoanode
      yielded a significant photocurrent density of approximately 12 mA/cm(2) at 0.4 V
      vs Ag/AgCl. The photocurrent and IPCE were enhanced compared to single quantum
      dot sensitized structures as a result of the band alignment of CdS and CdSe in
      electrolyte. Moreover, in comparison to single-sided cosensitized layered
      structures, this double-sided architecture that enables direct interaction
      between quantum dot and nanowire showed improved charge collection efficiency.
      Our result represents the first double-sided nanowire photoanode that integrates
      uniquely two semiconductor quantum dots of distinct band gaps for PEC hydrogen
      generation and can be possibly applied to other applications such as
      nanostructured tandem photovoltaic cells.

PMID- 20148568
TI  - Si/TiSi2 Heteronanostructures as high-capacity anode material for li ion
      batteries.
AB  - We synthesized a unique heteronanostructure consisting of two-dimensional TiSi(2)
      nanonets and particulate Si coating. The high conductivity and the structural
      integrity of the TiSi(2) nanonet core were proven as great merits to permit
      reproducible Li(+) insertion and extraction into and from the Si coating. This
      heteronanostructure was tested as the anode material for Li(+) storage. At a
      charge/discharge rate of 8400 mA/g, we measured specific capacities >1000 mAh/g.
      Only an average of 0.1% capacity fade per cycle was observed between the 20th and
      the 100th cycles. The combined high capacity, long capacity life, and fast
      charge/discharge rate represent one of the best anode materials that have been
      reported. The remarkable performance was enabled by the capability to preserve
      the crystalline TiSi2 core during the charge/discharge process. This achievement
      demonstrates the potency of this novel heteronanostructure design as an electrode
      material for energy storage.

PMID- 20148569
TI  - Novel aryl and heteroaryl acyl sulfamide synthesis via microwave-assisted
      palladium-catalyzed carbonylation.
AB  - A novel, simple synthesis of aryl and heteroaryl acyl sulfamides has been
      developed via palladium-catalyzed carbonylation of aryl or heteroaryl halides in
      the presence of sulfamide nucleophiles. A range of reactions illustrating the
      wide scope of this reaction was carried out under microwave irradiation in a
      vessel equipped with a gas inlet adapter and proceeded in good to excellent
      yields.

PMID- 20148570
TI  - Trigochinins A-C: three new daphnane-type diterpenes from Trigonostemon
      chinensis.
AB  - Three highly oxygenated new diterpenes, trigochinins A-C (1-3) were isolated from
      Trigonostemon chinensis. Their structures with the absolute configuration were
      determined by a spectroscopic method, X-ray crystallography, and CD analysis.
      This study suggested the revision of the C-6 stereochemistry of trigonothyrins A
      C reported quite recently. Compound 3 showed significant inhibition against MET
      tyrosine kinase activity with a IC(50) value of 1.95 microM.

PMID- 20148571
TI  - Synthesis of a sensitive and selective potassium-sensing fluoroionophore.
AB  - An efficient synthesis is reported that delivers in 5 steps and 52% overall yield
      a new structurally simplified fluorescent K(+) sensor with improved K(+)
      sensitivity and selectivity over existing K(+) sensors. The synthesis procedure
      utilizes a new template-directed oxidative C-N bond-forming macrocyclization
      reaction and reports new approaches to Pd(0), Sandmeyer-like and metal-free
      aminoarylations, as well as organotitanium additions to vinylogous sulfonates.

PMID- 20148572
TI  - Surface sampling by spray-desorption followed by collection for chemical
      analysis.
AB  - Desorption electrospray ionization (DESI) directly analyzes soluble chemical
      components present on surfaces when a pneumatically assisted electrospray is
      directed at the sample. Here we demonstrate that the same spray desorption
      mechanism that operates in DESI can be used as a general technique to collect
      soluble materials present on surfaces. After desorption analytes are collected on
      a suitable collection surface, large areas can be scanned and collected onto a
      small collected area, which allows for preconcentration of low abundance material
      before analysis. This collection surface can then subsequently be analyzed by
      DESI but also by many other techniques such as gas chromatography-mass
      spectrometry or UV-vis spectroscopy. In addition this technique can be used to
      study desorption mechanisms in DESI independently from ionization mechanisms.
      Preliminary results indicate that the optimized conditions in DESI are a
      compromise between those conditions that are optimum for desorption and
      conditions that lead to efficient ionization.

PMID- 20148573
TI  - Total synthesis of sintokamide C.
AB  - A convergent stereoselective synthesis of sintokamide C was accomplished in 14
      steps with an overall yield of 3.8% starting from Garner's aldehyde,
      unambiguously confirming its structure.

PMID- 20148574
TI  - Atomic resolution imaging and topography of boron nitride sheets produced by
      chemical exfoliation.
AB  - Here, we present a simple method for preparing thin few-layer sheets of hexagonal
      BN with micrometer-sized dimensions using chemical exfoliation in the solvent 1,2
      dichloroethane. The atomic structure of both few-layer and monolayer BN sheets is
      directly imaged using aberration-corrected high-resolution transmission electron
      microscopy. Electron beam induced sputtering effects are examined in real time.
      The removal of layers of BN by electron beam irradiation leads to the exposure of
      a step edge between a monolayer and bilayer region. We use HRTEM imaging combined
      with image simulations to show that BN bilayers can have AB stacking and are not
      limited to just AA stacking.

PMID- 20148575
TI  - Nano-optofluidic detection of single viruses and nanoparticles.
AB  - The reliable detection, sizing, and sorting of viruses and nanoparticles is
      important for biosensing, environmental monitoring, and quality control. Here we
      introduce an optical detection scheme for the real-time and label-free detection
      and recognition of single viruses and larger proteins. The method makes use of
      nanofluidic channels in combination with optical interferometry. Elastically
      scattered light from single viruses traversing a stationary laser focus is
      detected with a differential heterodyne interferometer and the resulting signal
      allows single viruses to be characterized individually. Heterodyne detection
      eliminates phase variations due to different particle trajectories, thus
      improving the recognition accuracy as compared to standard optical
      interferometry. We demonstrate the practicality of our approach by resolving
      nanoparticles of various sizes, and detecting and recognizing different species
      of human viruses from a mixture. The detection system can be readily integrated
      into larger nanofluidic architectures for practical applications.

PMID- 20148576
TI  - Complex fluids based on methacrylated hyaluronic acid.
AB  - We present the preparation and characterization of viscoelastic formulations of
      hyaluronic acid functionalized with polymerizable methacrylate groups. We
      explored three different processing strategies for controlling microstructure and
      interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked
      microspheres, and an elastic microgel formed through centrifuging the
      microspheres. The component structure and rheological properties of these
      formulations were compared to those of high molecular weight hyaluronic acid
      solutions, which displayed classical behavior of high molecular weight polymer
      solutions reported by other investigators. We demonstrate that these processing
      strategies allow the tuning of solution properties from strongly viscoelastic
      behavior, observed in lightly cross-linked near-gels and concentrated microsphere
      solutions to elastic behavior in elastic microgels, behaving like pseudoplastic
      liquids having a well-defined yield stress above which viscous behavior was
      observed. In the centrifuged microspheres, the hyaluronic acid degree of
      methacrylation was inversely proportional to the gel elasticity, and a mechanism
      based on failure due to microsphere brittleness is proposed to explain this
      behavior. These results suggest that processing methacrylated hyaluronic acid can
      lead to a diversity of solution properties, providing methods for delivering this
      biologically active polymer in a broad range of applications.

PMID- 20148578
TI  - Miniaturized system for rapid field inversion gel electrophoresis of DNA with
      real-time whole-gel detection.
AB  - Pulsed field gel electrophoresis (PFGE) methods have become standard tools in a
      wide range of DNA analysis applications. But many aspects of DNA migration
      phenomena under pulsed field conditions are not well understood as compared with
      the more conventional situation where the electric field is held constant. A key
      reason for this deficiency is that PFGE experiments are cumbersome to perform due
      to extremely long separation times (approximately 10-15 h) and the need to
      perform gel analysis by poststaining after completion of the run. Here we
      introduce an easy to build miniaturized slab gel apparatus that addresses these
      issues by enabling large DNA fragments up to 35 kb in length to be separated
      using field inversion gel electrophoresis (FIGE) in 60-90 min. The compact size
      of the device also allows the entire gel to be continuously monitored so that the
      separation processes can be imaged in real time using a high-resolution CCD
      camera. Arbitrary control over the applied voltage waveforms is achieved using a
      function generator interfaced with a high voltage amplifier. These capabilities
      allow us to probe the size dependence of fundamental physical parameters
      associated with DNA migration (mobility, diffusion, and separation resolution).
      These data reveal a surprising regime where separation resolution increases with
      DNA fragment size owing to a favorable interplay between mobility and diffusion
      scalings and highlight the important role of diffusion (a seldom quantified
      parameter). In addition to the practical benefit of separation times that are an
      order of magnitude faster than conventional instruments, the results of these
      studies provide a previously unavailable rational basis to identify optimal
      separation conditions and contribute new insights toward understanding the
      underlying physical processes that govern DNA electrophoresis in pulsed fields.

PMID- 20148579
TI  - Label-free colorimetric assay for methyltransferase activity based on a novel
      methylation-responsive DNAzyme strategy.
AB  - DNA methylation catalyzed by methyltransferase (MTase) is a significant
      epigenetic process for modulating gene expression. Traditional methods to study
      MTase activity require a laborious and costly DNA labeling process. In this
      article, we report a simple, colorimetric, and label-free methylation-responsive
      DNAzyme (MR-DNAzyme) strategy for MTase activity analysis. This new strategy
      relies on horseradish peroxidase (HRP) mimicking DNAzyme and the methylation
      responsive sequence (MRS) of DNA which can be methylated and cleaved by the
      MTase/endonuclease coupling reaction. Methylation-induced scission of MRS would
      activate the DNAzyme that can catalyze the generation of a color signal for the
      amplified detection of methylation events. Taking Dam MTase and DpnI endonuclease
      as examples, we have developed two colorimetric methods based on the MR-DNAzyme
      strategy. The first method is to utilize an engineered hairpin-DNAzyme hybrid
      probe for facile turn-on detection of Dam MTase activity, with a wide linear
      range (6-100 U/mL) and a low detection limit (6 U/mL). Furthermore, this method
      could be easily expanded to profile the activity and inhibition of restriction
      endonuclease. The second method involves a methylation-triggered DNAzyme-based
      DNA machine, which achieves the ultrahigh sensitive detection of Dam MTase
      activity (detection limit = 0.25 U/mL) by a two-step signal amplification
      cascade.

PMID- 20148580
TI  - Prediction of electron-transfer/capture dissociation spectra of peptides.
AB  - An empirical model, based on classic kinetics, was developed for quantitative
      prediction of electron-transfer dissociation (ETD) and electron-capture
      dissociation (ECD) spectra of peptides. The model includes most fragmentation
      pathways described in the literature plus some additional pathways based on the
      author's assumptions and observations. The ETD model was trained with more than
      7000 ETD spectra, with and without supplemental activation. The ECD model was
      trained with more than 6000 ECD spectra. The trained ETD and ECD models are able
      to predict ETD and ECD spectra with reasonable accuracy in ion intensities for
      peptide precursors up to 4000 u in mass.

PMID- 20148581
TI  - Prescribed fire as a means of reducing forest carbon emissions in the western
      United States.
AB  - Carbon sequestration by forested ecosystems offers a potential climate change
      mitigation benefit. However, wildfire has the potential to reverse this benefit
      In the western United States, climate change and land management practices have
      led to increases in wildfire intensity and size. One potential means of reducing
      carbon emissions from wildfire is the use of prescribed burning,which consumes
      less biomass and therefore releases less carbon to the atmosphere. This study
      uses a regional fire emissions model to estimate the potential reduction in fire
      emissions when prescribed burning is applied in dry, temperate forested systems
      of the western U.S. Daily carbon dioxide (CO(2)) fire emissions for 2001-2008
      were calculated for the western U.S. for two cases: a default wildfire case and
      one in which prescribed burning was applied. Wide-scale prescribed fire
      application can reduce CO(2) fire emissions for the western U.S. by 18-25%1 in
      the western U.S., and by as much as 60% in specific forest systems. Although this
      work does not address important considerations such as the feasibility of
      implementing wide-scale prescribed fire management or the cumulative emissions
      from repeated prescribed burning, it does provide constraints on potential carbon
      emission reductions when prescribed burning is used.

PMID- 20148582
TI  - Characterization of the single particle mixing state of individual ship plume
      events measured at the Port of Los Angeles.
AB  - Ship emissions contribute significantly to gaseous and particulate pollution
      worldwide. To better understand the impact of ship emissions on air quality,
      measurements of the size-resolved chemistry of individual particles in ship
      emissions were made at the Port of Los Angeles using real-time, single-particle
      mass spectrometry. Ship plumes were identified through a combination of ship
      position information and measurements of gases and aerosol particles at a site
      500 m from the center of the main shipping channel at the Port of Los Angeles.
      Single particles containing mixtures of organic carbon, vanadium, and sulfate (OC
      V-sulfate) resulted from residual fuel combustion (i.e., bunker fuel), whereas
      high quantities of fresh soot particles (when OC-V-sulfate particles were not
      present) represented distinct markers for plumes from distillate fuel combustion
      (i.e., diesel fuel) from ships as well as trucks in the port area. DC-V-sulfate
      particles from residual fuel combustion contained significantly higher levels of
      sulfate and sulfuric acid than plume particles containing no vanadium. These
      associations may be due to vanadium (or other metals such as iron) in the fuel
      catalyzing the oxidation of S0(2) to produce sulfate and sulfuric acid on these
      particles. Enhanced sulfate production on OC-V-sulfate ship emission particles
      would help explain some of the higher than expected sulfate levels measured in
      California compared to models based on emissions inventories and typical sulfate
      production pathways. Understanding the overall impact of ships emissions is
      critical for controlling regional air quality in the many populated coastal
      regions of the world.

PMID- 20148583
TI  - Label-free biomarker sensing in undiluted serum with suspended microchannel
      resonators.
AB  - Improved methods are needed for routine, inexpensive monitoring of biomarkers
      that could facilitate earlier detection and characterization of cancer. Suspended
      microchannel resonators (SMRs) are highly sensitive, batch-fabricated
      microcantilevers with embedded microchannels that can directly quantify adsorbed
      mass via changes in resonant frequency. As in other label-free detection methods,
      biomolecular measurements in complex media such as serum are challenging due to
      high background signals from nonspecific binding. In this report, we demonstrate
      that carboxybetaine-derived polymers developed to adsorb directly onto SMR SiO(2)
      surfaces act as ultralow fouling and functionalizable surface coatings. Coupled
      with a reference microcantilever, this approach enables detection of activated
      leukocyte cell adhesion molecule (ALCAM), a model cancer biomarker, in undiluted
      serum with a limit of detection of 10 ng/mL.

PMID- 20148584
TI  - Optical monitoring of gases with cholesteric liquid crystals.
AB  - A new approach to optical monitors for gases is introduced using cholesteric
      liquid crystals doped with reactive chiral compounds. The approach is based on
      cholesteric pitch length changes caused by a change in helical twisting power
      (HTP) of the chiral dopants upon reaction with the analyte. The concept is
      demonstrated for monitoring carbon dioxide via reversible carbamate formation and
      for oxygen using the irreversible oxidation of a chiral dithiol to a disulfide.
      Monitoring of CO(2) was achieved by doping a commercial cholesteric liquid
      crystalline mixture (E7) with 1.6% mol of the 1:1 complex of an optically pure
      diamine with a TADDOL derivative. Upon exposure to carbon dioxide, the reflection
      band of a thin film of the mixture shifted from 637 to 495 nm as a consequence of
      dissociation of the complex after carbamate formation of the diamine. An O(2)
      monitor was obtained by doping E7 with a chiral binaphthyl dithiol derivative and
      a nonresponsive codopant. The reflection band of the oxygen monitor film changed
      from 542 to 600 nm, due to the conformational change accompanying oxidation of
      the dithiol to disulfide. These monitoring mechanisms hold promise for
      application in smart packaging, where carbon dioxide and oxygen are of special
      interest because of their roles in food preservation.

PMID- 20148585
TI  - Total synthesis of (+)-fendleridine (aspidoalbidine) and (+)-1
      acetylaspidoalbidine.
AB  - A total synthesis of the Aspidosperma alkaloids (+)-fendleridine and (+)-1
      acetylaspidoalbidine is detailed, providing access to both enantiomers of the
      natural products and establishing their absolute configuration. Central to the
      synthetic approach is a powerful intramolecular [4+2]/[3+2] cycloaddition cascade
      of a 1,3,4-oxadiazole in which the pentacyclic skeleton and all the
      stereochemistry of the natural products are assembled in a reaction that forms
      three rings, four C-C bonds, and five stereogenic centers including three
      contiguous quaternary centers, and introduces the correct oxidation state at C19
      in a single synthetic operation. The final tetrahydrofuran bridge is subsequently
      installed in one step, enlisting an intramolecular alcohol addition to an iminium
      ion generated by nitrogen-assisted opening of the cycloadduct oxido bridge, with
      a modification that permits release of useful functionality (a ketone) at the
      cleavage termini.

PMID- 20148587
TI  - Dynamics of 1,3-dipolar cycloadditions: energy partitioning of reactants and
      quantitation of synchronicity.
AB  - The dynamics of 1,3-dipolar cycloadditions of nine 1,3-dipoles with ethylene and
      acetylene have been explored by quasiclassical trajectory and single trajectory
      calculations in the retro-cycloaddition direction to compute energy partitioning
      of reactants among relative translation, vibration, and rotation. The results are
      interpreted with an expanded version of Polanyi's Rules for bimolecular
      reactions, and three trends are evident. (1) Relative translation of reactants is
      the main contributor to surmounting the barrier, since all transition states
      (TSs) are early with respect to sigma bond formation. (2) Vibrational excitation
      in the 1,3-dipole bending modes required for reaction is related to the lateness
      of the TS with respect to dipole bending: diazonium betaines (late TS, dipole
      bending required) > nitrilium betaines > azomethine betaines (early TS, dipole
      bending least important). This is also the order of the activation barriers (high
      --> low). (3) The previously reported linear correlation between activation
      barriers and the energy required to distort reactants to their TS geometries are
      understandable in terms of the requirements for vibrational excitation computed
      here. For the 1,3-dipolar cycloadditions, single trajectory calculations, which
      contain no zero point vibrational energy, give reasonable estimates of the mean
      energy partitioning of reactants derived from potential energy barrier release.
      The timing of bond formation and relative reactivities of different 1,3-dipoles
      are discussed.

PMID- 20148586
TI  - Steering S-H and N-H bond activation by a stable n-heterocyclic silylene:
      different addition of H(2)S, NH(3), and organoamines on a silicon(II) ligand
      versus its Si(II)-->Ni(CO)(3) complex.
AB  - The strikingly different behavior of the ylide-like, N-heterocyclic silylene LSi:
      (5: L = CH[(C horizontal lineCH(2))CMe(NAr)(2)]; Ar = 2,6-(i)PrC(6)H(3)) versus
      its LSi-->Ni(CO)(3) complex 13 to activate E-H bonds (E = S, N) of small
      molecules is reported. Remarkably, conversion of 5 with hydrogen sulfide leads
      exclusively to the first isolable silathioformamide, L'Si( horizontal lineS)H
      (16: L' = CH[C(Me)NAr](2); Ar = 2,6-(i)PrC(6)H(3)) with a donor-supported Si
      horizontal lineS double bond and four-coordinate silicon. The latter result
      demonstrates the unusual ambivalent reactivity of 5 by combining two modes of
      reactivity involving S-H bond activation and subsequent 1,4- and 1,1-addition,
      respectively. In addition, 5 can serve as a ligand with well-balanced sigma-donor
      and pi-acceptor capabilities toward transition metals. This has been demonstrated
      by the isolable [Ni(0)(arene)] complexes 12a-e (arene = Me(n)C(6)H(6-n), n = 0
      3), which are ideal precursors for the formation of the corresponding Ni(CO)(3)
      complex 13. The latter activates a S-H bond in hydrogen sulfide, too, but the
      presence of the Ni(CO)(3) moiety governs the formation of the complex 17, bearing
      an unprecedented beta-diketiminate silicon(II) thiol ligand: L'Si(SH): (L' =
      CH[C(Me)NAr](2); Ar = 2,6-(i)PrC(6)H(3)). Likewise, the Si(II)-->Ni(CO)(3)
      coordination in 13 steers exclusively 1,4-addition of ammonia, isopropylamine,
      and phenylhydrazine onto the silylene ligand 5, leading to the corresponding beta
      diketiminate silicon(II) amide or hydrazide complexes L'Si(NHR)-->Ni(CO)(3) (23a
      c: R = H, (i)Pr, N(H)Ph). IR measurements reveal that the carbonyl stretching
      frequencies of the Ni(CO)(3) moiety in 23a-c are shifted to even lower
      wavenumbers in comparison to those of NHCs or phosphines. In other words, the
      beta-diketiminate silicon(II) amide ligands in 23a-c represent the strongest
      donors in the series of N-heterocyclic silylenes reported as yet.

PMID- 20148588
TI  - Electrochemical responses and electrocatalysis at single au nanoparticles.
AB  - Steady-state electrochemical responses have been obtained at single Au
      nanoparticles using Pt nanoelectrodes. A Au single-nanoparticle electrode (SNPE)
      is constructed by chemically immobilizing a single Au nanoparticle at a SiO(2)
      encapsulated Pt disk nanoelectrode, which was previously modified by an amine
      terminated silane. The Au SNPE has been characterized by transmission electron
      microscopy, underpotential deposition of Cu, and steady-state cyclic voltammetry.
      It has been found that the presence of a single Au nanoparticle enhances the
      electron transfer from the Pt nanoelectrode to the redox molecules, and the
      voltammetric response at the Au SNPE depends on the size of the Au nanoparticle.
      The Au SNPE has been utilized to examine the oxygen-reduction reaction in a KOH
      solution to explore the feasibility of measuring the electrocatalytic activity at
      a single-nanoparticle level. It has been shown that the electrocatalytic activity
      of single Au nanoparticles can be directly measured using SNPEs, and the
      electrocatalytic activity is dependent on the size of the Au nanoparticles. This
      study can help to understand the structure-function relationship in nanoparticle
      based electrocatalysis.

PMID- 20148589
TI  - Protonated [4n]pi and [4n+2]pi octaphyrins choose their Mobius/Huckel aromatic
      topology.
AB  - Protonation-triggered conformational changes of meso-octakis(pentafluorophenyl)
      [36]octaphyrin and [38]octaphyrin have been investigated. The X-ray crystal
      structures and (1)H NMR analyses revealed that the protonation process cuts off
      intramolecular hydrogen bonds between aminic and iminic pyrrole units and, at the
      same time, produces intermolecular hydrogen-bond network between aminic pyrrole
      unit and counter-anions. Such a replacement induces some pyrrole inversion,
      leading to Mobius aromatic conformation for [36]octaphyrin and to Huckel aromatic
      conformation for [38]octaphyrin. These protonated octaphyrins show similar
      structures only with a subtle difference in tilted pyrrole angles, which results
      in their different topologies. This feature strongly suggests that the
      macrocycles control their topologies by pyrrole rotation to gain [4n]pi Mobius or
      [4n+2]pi Huckel aromatic stabilization, depending on the number of pi-electrons.
      Detailed photophysical properties such as absorption/fluorescence, excited
      singlet/triplet state lifetimes, and two-photon absorption cross-section values
      have been presented for both protonated [36] and [38]octaphyrins in conjunction
      with their Mobius or Huckel aromaticity.

PMID- 20148590
TI  - Conductometric method for the rapid characterization of the substrate specificity
      of amine-transaminases.
AB  - Amine-transaminases (ATAs, omega-transaminases, omega-TA) are PLP-dependent
      enzymes that catalyze amino group transfer reactions. In contrast to the
      widespread and well-known amino acid-transaminases, ATAs are able to convert
      substrates lacking an alpha-carboxylic functional group. They have gained
      increased attention because of their potential for the asymmetric synthesis of
      optically active amines, which are frequently used as building blocks for the
      preparation of numerous pharmaceuticals. Having already introduced a fast kinetic
      assay based on the conversion of the model substrate alpha-methylbenzylamine for
      the characterization of the amino acceptor specificity, we now report on a
      kinetic conductivity assay for investigating the amino donor specificity of a
      given ATA. The course of an ATA-catalyzed reaction can be followed
      conductometrically since the conducting substrates, a positively charged amine
      and a negatively charged keto acid, are converted to nonconducting products, a
      noncharged ketone and a zwitterionic amino acid. The decrease of conductivity for
      the investigated reaction systems were determined to be 33-52 microS mM(-1). In
      contrast to other ATA-assays previously described, with this approach all
      transamination reactions between any amine and any keto acid can be monitored
      without the need for an additional enzyme or staining solutions. The assay was
      used for the characterization of a ATA from Rhodobacter sphaeroides, and the data
      obtained were in excellent agreement with gas chromatography analysis.

PMID- 20148591
TI  - A class-specific enzyme-linked immunosorbent assay based on magnetic particles
      for multiresidue organophosphorus pesticides.
AB  - A magnetic particle-based enzyme-linked immunosorbent assay (mp-ELISA) to detect
      multiresidue organophosphorus pesticides (OPs) was developed and evaluated in
      parallel with a conventional competitive indirect ELISA utilizing the same pair
      of antibodies. The antibody was immobilized by chemical coupling on the
      ferroferric oxide nanoparticles coated with 3-aminopropyl triethoxysilane
      (APTES). Comparative studies demonstrated that mp-ELISA exhibited both
      significantly improved sensitivity and better class specificity than conventional
      ELISA, although the reproducibility and repeatability of the two assays were
      equivalent. As compared with data from the conventional ELISA, the averages of
      the midpoint inhibition (IC(50)) decreasing rate of mp-ELISA were 81.1 and 62.1%
      for the magnetic first antibody (MFA) and magnetic second antibody (MSA),
      respectively. The class specificity of MFA was broader than that of MSA. The
      results demonstrated the high potential of mp-ELISA based on the MFA as a tool to
      improve sensitivity and broad specificity in multiresidue immunoassay.

PMID- 20148592
TI  - N-heterocyclic carbene-amine Pt(II) complexes, a new chemical space for the
      development of platinum-based anticancer drugs.
AB  - N-Heterocyclic carbene (NHC) platinum complexes have been highlighted as a
      promising and original platform for building new cytotoxic drugs of the cisplatin
      series. Mixed NHC-amine Pt(II) complexes have been prepared via a facile and
      modular two step sequence leading to trans-configured square planar species. They
      have been characterized by spectroscopic methods and X-ray diffraction studies.
      Their efficiency against both cisplatin sensitive (CEM and H460) and resistant
      (A2780/DDP, CH1/DDP, and SK-OV-3) cell lines has been demonstrated by in vitro
      experiments.

PMID- 20148593
TI  - P-glycoprotein antibody functionalized carbon nanotube overcomes the multidrug
      resistance of human leukemia cells.
AB  - Multidrug resistance (MDR), which is related to cancer chemotherapy, tumor stem
      cells, and tumor metastasis, is a huge obstacle for the effective cancer therapy.
      One of the underlying mechanisms of MDR is the increased efflux of anticancer
      drugs by overexpressed P-glycoprotein (P-gp) of multidrug resistant cells. In
      this work, the antibody of P-gp (anti-P-gp) functionalized water-soluble single
      walled carbon nanotubes (Ap-SWNTs) loaded with doxorubicin (Dox), Dox/Ap-SWNTs,
      were synthesized for challenging the MDR of K562 human leukemia cells. The
      resulting Ap-SWNTs could not only specifically recognize the multidrug resistant
      human leukemia cells (K562R), but also demonstrate the effective loading and
      controllable release performance for Dox toward the target K562R cells by
      exposing to near-infrared radiation (NIR). The recognition capability of Ap-SWNTs
      toward the K562R cells was confirmed by flow cytometry (FCM) and confocal laser
      scanning microscopy (CLSM). The binding affinity of Ap-SWNTs toward drug
      resistant K562R cells was ca. 23-fold higher than that toward drug-sensitive
      K562S cells. Additionally, CLSM indicated that Ap-SWNTs could specifically
      localize on the cell membrane of K562R cells and the fluorescence of Dox in K562R
      cells could be significantly enhanced after the employment of Ap-SWNTs as
      carrier. Moreover, the composite of Dox and Ap-SWNTs (Dox/Ap-SWNTs) expressed 2.4
      fold higher cytotoxicity and showed the significant cell proliferation
      suppression toward K562R leukemia cells (p < 0.05) as compared with free Dox
      which is popularly employed in clinic trials. These results suggest that the Ap
      SWNTs are the promising drug delivery vehicle for overcoming the MDR induced by
      the overexpression of P-gp on cell membrane. Ap-SWNTs loaded with drug molecules
      could be used to suppress the proliferation of multidrug resistant cells, destroy
      the tumor stem cells, and inhibit the metastasis of tumor.

PMID- 20148594
TI  - Capillary isoelectric focusing with an open tubular immobilized pH gradient.
AB  - Capillary isoelectric focusing (CIEF) was first performed in an open tubular
      mode. It depended on an immobilized pH gradients from the polymerization of
      several solutions, which contained acrylamide, N,N'-methylenebisacrylamide,
      allylamine, and acrylic acid. Different ratios of the basic and acidic monomers
      lead to solutions of various pHs. When injected into a capillary in the sequence
      of their pHs, the solutions polymerized and resulted into polymers with a series
      of isoelectric points (pIs). These polymers formed a covalently attached
      hydrophilic layer in the capillary, acting as both column bonding and carrier
      ampholytes. When five polymers were orderly lined up in a capillary, an
      immobilized pH gradient was established. This open tubular column was subjected
      to CIEF, showing excellent performance properties for protein focusing.

PMID- 20148595
TI  - Plasmon resonance spectroscopy of gold-in-gallium oxide peapod and core/shell
      nanowires.
AB  - Light-scattering properties of individual gold-in-Ga(2)O(3) peapod nanowires and
      gold-in-Ga(2)O(3) core/shell nanowires were investigated by optical dark-field
      microscopy. The observed scattering peaks are suggested to result from plasmonic
      resonance of the gold nanopeas and nanorods in the Ga(2)O(3) nanowires. As the
      diameter of gold peapod increases, the resonance peak of the optical scattering
      spectra showed a red-shift. In addition, as the gold peas are elongated along one
      axis, the corresponding plasmon resonance peak splits into two peaks at shorter
      and longer wavelengths. The cladding Ga(2)O(3) dielectric layer also plays a key
      role in light-scattering behavior. The observed modulation in the p-polarized
      spectrum revealed that future vertical nanoplasmonic devices made by plasmonic
      nanocavity due to the short propagation length of surface plasmons can be
      realized and optimized.

PMID- 20148596
TI  - Swelling of ionic and nonionic surfactant micelles by high pressure gases.
AB  - The influence of different solvent environments on the size, shape, and
      characteristics of surfactant micelles of Pluronic F127 and CTAB was investigated
      by small-angle neutron scattering (SANS). SANS experiments were undertaken on
      dilute micellar surfactant solutions of F127 and CTAB that between them were
      exposed to liquid and supercritical carbon dioxide, liquid propane, ethane, and
      heptane under various pressures and temperatures. Swelling of the surfactant
      micelles could be directly related to the solubility of the solvents within the
      micelles, especially within their cores. Carbon dioxide produced the largest
      swelling of the Pluronic F127 micelles, compared to propane and ethane, which
      mirrors the solubility of the gases in the PPO core of the micelles. Conversely,
      the extent of swelling of the cores of CTAB micelles was greater with propane
      compared to carbon dioxide, which again relates to the solubility of the solvents
      in the alkane core of the CTAB micelles.

PMID- 20148597
TI  - Poly(allylamine)-stabilized colloidal copper nanoparticles: synthesis,
      morphology, and their surface-enhanced Raman scattering properties.
AB  - Poly(allylamine)-stabilized spherical- and rod-shaped copper nanoparticles are
      synthesized by a simple chemical reaction. The synthesis is performed by the
      reduction of copper(II) salt with hydrazine in aqueous solution under atmospheric
      air in the presence of poly(allylamine) (PAAm) capping agent. Noteworthy of the
      advantages of the synthetic method includes its production of water dispersible
      copper nanoparticles at room temperature under no inert atmosphere, making the
      synthesis more environmentally friendly. The resulting copper nanoparticles are
      investigated by UV-vis spectroscopy and transmission electron microscopy (TEM).
      The results demonstrate that the amount of NaOH used is important for the
      formation of the copper nanoparticles while the reaction time and concentration
      of PAAm play key roles in controlling the size and shape of the nanoparticles,
      respectively. The resulting colloidal copper nanoparticles exhibit large surface
      enhanced Raman scattering (SERS) signals.

PMID- 20148598
TI  - Immunoproteomic identification of polyvalent vaccine candidates from Vibrio
      parahaemolyticus outer membrane proteins.
AB  - Bacterium is still a major cause of many infectious diseases and a global threat
      to human health, aquaculture, and animal feeding. Prevention by vaccination is
      the most efficient and economical way of fighting bacterial diseases, but one of
      the persistent challenges to prevent bacterial infections and disease
      transmissions is the existence of multiple bacterial species, families, and
      genera and the lack of efficient polyvalent vaccines against them. The
      information on candidate immunogens for polyvalent vaccine development is
      elusive, as well. For the development of broad cross-protective vaccines, we have
      employed heterogeneous antiserum-based immunoproteomics approaches to identify
      antigenically similar outer membrane (OM) proteins that could be used as
      potential polyvalent vaccine candidates against Vibrio parahaemolyticus , V.
      alginolyticus , V. fluvialis , Aeromonas hydrophila , and A. sobria infections.
      VPA1435, VP0764, VPA1186, VP1061, and VP2850 could be recognized by at least
      three antisera and demonstrated significantly passive and active immune
      protection against V. parahaemolyticus infection in a crucian carp model. VP1061
      and VP2850 induced higher immune and protective abilities than the other three OM
      proteins. Furthermore, the abilities of VP1061 and VP2850 in the generation of
      broad cross-protective immune reaction against the infections of V. alginolyticus
      , A. hydrophila , and Pseudomonas fluorescens were also investigated in fish and
      mouse models. Our results suggested that VP1061 and VP2850 could potentially be
      used as polyvalent vaccine candidates for the development of novel polyvalent
      vaccines against V. parahaemolyticus and other Gram-negative pathogens. On the
      basis of these results, characteristics of OM proteins as polyvalent vaccine
      candidates have been addressed.

PMID- 20148599
TI  - Comparison of HTN management in patients with diabetes between rural and urban
      primary care clinics in Northeastern Colorado - a report from SNOCAP.
AB  - INTRODUCTION: In the USA, rural residents have a higher burden of disease and
      more limited access to care than urban residents. There are conflicting data on
      quality of care in rural settings. To evaluate this relationship, blood pressure
      (BP) control and decision-making at the point of care in patients with diabetes
      were examined for rural and urban medical providers in Northeastern Colorado.
      METHODS: Twenty-six primary care practices in two practice-based research
      networks in Colorado participated: 13 in rural settings and 13 urban.
      Questionnaires were completed after each encounter with an adult with type 2
      diabetes. The survey obtained: (1) demographic information; (2) BP result; (3)
      whether action was taken; (4) if action was taken, type of action; and (5) if no
      action, what reasons were given for this inaction. Bivariate and multivariate
      analyses were performed to identify predictors of action. RESULTS: In total, 778
      surveys were completed. Mean BP was 130/74 (+/-18.8/12.0) with BP in rural
      residents being slightly lower than for urban residents. Rural residents were
      more likely to be non-Hispanic white, on Medicare, on multiple medications, and
      less likely to be on Medicaid. Sixty-five percent of urban patients exceeded BP
      goals, as did 58% of rural patients. Action rates for those with elevated BP in
      rural areas were not significantly different than those in urban areas (OR 0.75
      [0.45-1.25] p = 0.27). The reasons for inaction were similar. CONCLUSION: In this
      study of patients with diabetes, quality of care for elevated BP was similar in
      rural and urban areas.

PMID- 20148600
TI  - Clinical guidelines and performance measures.

PMID- 20148601
TI  - New diabetes HEDIS blood pressure quality measure: potential for overtreatment.
AB  - OBJECTIVE: To examine reasons for failing to meet the new Healthcare
      Effectiveness Data and Information Set (HEDIS) blood pressure (BP) measure for
      diabetes patients (BP <130/80 mm Hg), which may not accurately identify poor
      quality care and could promote overtreatment through its performance incentives.
      STUDY DESIGN: Retrospective chart review. METHODS: We formed 2 cohorts of
      diabetes patients in 9 general medicine clinics in an academic healthcare system.
      Cohort A (n = 124) failed the new HEDIS measure but passed the old measure
      (systolic blood pressure [SBP] 130-139 and diastolic blood pressure [DBP] <90 mm
      Hg; or SBP <140 and DBP 80-89 mm Hg). Cohort B (n = 125) failed the old measure
      (SBP > or = 140 and/ or DBP > or = 90). We reviewed medical records to ascertain
      clinician response to elevated BP. RESULTS: Physicians documented treatment
      changes in only 4% and 28% of cohort A and B patients, respectively. Refractory
      systolic hypertension was common in those aged > or = 65 years; 60% of those in
      cohort B and 58% in cohort A took 3 or more antihypertensive medications and/or
      had a diastolic BP below 70 mm Hg. CONCLUSIONS: We identified a substantial
      cohort of elderly diabetes patients with DBP <70 mm Hg who were on 3 medications
      at adequate doses, but who did not meet the current performance measurement
      criteria (140/90 or 130/80 mm Hg). We suggest that such patients be excluded from
      performance measures, or if included, be noted for special attention by
      clinicians to balance intensification with risk.

PMID- 20148602
TI  - "All-or-none" (bundled) process and outcome indicators of diabetes care.
AB  - OBJECTIVES: To evaluate processes and outcomes of diabetes care using bundled
      indicators from a primary care registry of osteopathic training programs. STUDY
      DESIGN: Retrospective cohort analysis. METHODS: This study examined care
      delivered to 7333 patients across 95 family practice and internal medicine
      residency programs (July 1, 2005, through September 15, 2008) to determine
      diabetes care performance using measures of processes of care and outcomes. Two
      summary (bundled) reports of care for each measure were constructed. The first
      used the frequency of indicated care delivered (indicator-level bundle), and the
      second used the frequency of patients' receiving all indicated care (patient
      level bundle). RESULTS: Use of the indicator-level bundle demonstrated that
      outcomes goals were achieved at a rate of 44.5%. Use of the patient-level bundle
      demonstrated that outcomes goals were achieved at a rate of only 16.2%, a
      significant difference (P <.001). Eight evidence-based processes of diabetes care
      were then examined using the 2 bundling methods. The indicator-level analysis
      mean rate for the bundled processes of care was 77.3%, whereas the patient-level
      analysis mean rate was only 33.5%. This was also significantly different (P
      <.001). CONCLUSIONS: The method of bundling care measures can have a profound
      effect on the reporting of goals achieved. This can in turn influence the
      assessment of provider performance and opportunity gaps in diabetes care
      delivery. In this study, providers were more likely to achieve processes-of-care
      goals when diabetes care was bundled at the indicator level than at the patient
      level. Standardization of summary reporting of diabetes care should be developed
      to enhance consistent interpretation of performance.

PMID- 20148603
TI  - Mail-order pharmacy use and adherence to diabetes-related medications.
AB  - OBJECTIVE: To investigate whether patients who use mail-order pharmacies were
      more likely to have good medication adherence than patients who use local
      pharmacies. STUDY DESIGN: Cross-sectional investigation. METHODS: We conducted
      cross-sectional analyses of patients from the Kaiser Permanente Northern
      California (KPNC) diabetes registry who received a new antiglycemic,
      antihypertensive, or lipid-lowering index medication between January 1, 2006, and
      May 31, 2006. We defined good adherence as medication availability at least 80%
      of the time (ie, a continuous measure of medication gaps value of < or = 20%) and
      compared adherence between mail-order users (> or = 66% of refills by mail) and
      KPNC local pharmacy users (all refills in person). Adherence was calculated from
      the initial dispensing through 15 months of follow-up, medication
      discontinuation, or May 31, 2007, whichever came first. We analyzed the data
      using multivariate logistic regression models, after determining that unmeasured
      patient-level factors and self-selection did not significantly bias our analyses.
      RESULTS: A total of 13,922 eligible patients refilled an index medication.
      Compared with those who used only local KPNC pharmacies, patients who received
      medications by mail were more likely to have good adherence (84.7% vs 76.9%, P
      <.001). After adjusting for potential confounders, including days' supply and out
      of-pocket costs, mailorder users had better adherence to antiglycemic,
      antihypertensive, and lipid-lowering medications (P <.001 for all). CONCLUSIONS:
      Compared with patients who obtained medication refills at local pharmacies,
      patients who received them by mail were more likely to have good adherence. The
      association between mail-order use and medication adherence should be evaluated
      in a randomized clinical trial.

PMID- 20148604
TI  - Leveling the field: addressing health disparities through diabetes disease
      management.
AB  - OBJECTIVES: To examine the relationships among patient characteristics, labor
      inputs, and improvement in glycosylated hemoglobin (A1C) level in a successful
      primary care-based diabetes disease management program (DDMP). STUDY DESIGN: We
      performed subanalyses to examine the relationships among patient characteristics,
      labor inputs, and improvement in A1C level within a randomized controlled trial.
      Control patients received usual care, while intervention patients received usual
      care plus a comprehensive DDMP. METHODS: The primary outcome was improvement in
      A1C level over 12 months stratified by intervention status and patient
      characteristics. Process outcomes included the number of actions or contacts with
      patients, time spent with patients, and number of glucose medication titrations
      or additions. RESULTS: One hundred ninety-three of 217 enrolled patients (88.9%)
      had complete 12-month followup data. Patients in the intervention group had
      significantly greater improvement in A1C level than the control group (-2.1% vs 
      1.2%, P = .007). In multivariate analysis, no significant differences were
      observed in improvement in A1C level when stratified by age, race/ethnicity,
      income, or insurance status, and no interaction effect was observed between any
      covariate and intervention status. Among intervention patients, we observed
      similar labor inputs regardless of age, race/ethnicity, sex, education, or
      whether goal A1C level was achieved. CONCLUSIONS: Among intervention patients in
      a successful DDMP, improvement in A1C level was achieved regardless of age,
      race/ethnicity, sex, income, education, or insurance status. Labor inputs were
      similar regardless of age, race/ethnicity, sex, or education and may reflect the
      nondiscriminatory nature of providing algorithm-based disease management care.

PMID- 20148605
TI  - Is there a survival benefit within a German primary care-based disease management
      program?
AB  - OBJECTIVE: To compare the mortality rate of patients with type 2 diabetes who
      were enrolled in the German diabetes disease management program (DMP) with the
      mortality rate of those who were not enrolled. STUDY DESIGN: This observational
      study was part of the ELSID study (Evaluation of a Large Scale Implementation of
      disease management programs) in Germany. METHODS: Participants had type 2
      diabetes and were either enrolled or not enrolled in the DMP. The DMP provides
      systems-based, multifaceted, and patient-centered interventions. To reduce
      imbalances between the groups, a matched sample was created using sex, age,
      retirement status, federal state, pharmacy-based cost groups, and diagnostic-cost
      groups as matching criteria. Cox proportional hazards regression model and the
      Kaplan-Meier method were used to assess overall mortality. The observation period
      was 3 years beginning on January 1, 2006. RESULTS: A total of 11,079 patients
      were included in the analysis. As of January 1, 2006, 2300 patients were enrolled
      in the DMP and 8779 were receiving routine care. There were 1927 matched pairs of
      patients in the DMP group and the non-DMP group. The overall mortality rate was
      11.3% in the DMP and 14.4% in the non-DMP group (log-rank test P <.01).
      CONCLUSIONS: We found an association between participation in the German diabetes
      DMP and reduced mortality. This reduced mortality cannot be attributed directly
      to the DMP. However, further research should evaluate whether a primary care
      based DMP contributes to increased life expectancy in patients with diabetes.

PMID- 20148606
TI  - Physician utilization by insurance type among youth with type 2 diabetes.
AB  - OBJECTIVE: To evaluate the relationship between insurance type (Medicaid vs
      private insurance) and access to physician care for youth with type 2 diabetes
      mellitus by quantifying whether these youth saw a physician during the year
      before their first diabetes documentation. STUDY DESIGN: Retrospective cohort
      study. METHODS: Youth with Medicaid or private insurance aged 5 to 19 years with
      type 2 diabetes were identified by an electronic medical record review. The first
      indication of type 2 diabetes defined the index date. Youth with type 1 diabetes
      and female patients with polycystic ovaries were excluded. Descriptive statistics
      evaluated differences in office visits before the index date between patients
      with the 2 insurance types. Multivariate logistic regression analysis evaluated
      the likelihood of having an office visit during the year before the index date
      among youth with Medicaid versus private insurance, controlling for youth
      characteristics. RESULTS: Of 2496 included youth, 400 (16.0%) had Medicaid
      coverage. More than 60% were female, the mean age was 14.5 years, and 68.8% were
      obese. On average, youth had 1.9 office visits during the year before the index
      date. Medicaid-covered youth were not significantly less likely to have had an
      office visit (odds ratio, 0.77; P = .09) or fewer total office visits (incident
      rate ratio, 1.13; P = .16) during the year before the index date. CONCLUSIONS:
      The likelihood of youth with type 2 diabetes and a source of physician care
      having a physician office visit during the year before the index date did not
      differ between patients with Medicaid versus private insurance. This suggests
      that the amount of physician care before diagnosis of type 2 diabetes does not
      differ for Medicaid-covered youth if they can establish a source of care.
      Additional research is investigating whether physician access before diagnosis is
      associated with access to diabetes-related care after diagnosis.

PMID- 20148607
TI  - A pay-for-performance program for diabetes care in Taiwan: a preliminary
      assessment.
AB  - OBJECTIVE: To examine the effects of a pay-for-performance (P4P) program for
      diabetes care in Taiwan. STUDY DESIGN: A population-based natural experimental
      design with intervention and comparison groups. METHODS: Healthcare service and
      expense data were extracted from the Taiwanese Bureau of National Health
      Insurance claim files for 2005 and 2006. The number of essential diabetes
      specific exams/tests, healthcare utilization, and pre- and post-intervention
      expenses were calculated for patients grouped according to P4P status. However,
      no clinical information was available for analysis. Difference-in-difference
      analysis was used in statistical regression models with proper distributions for
      these measures. RESULTS: Patients in the P4P program (n = 12,499) received
      significantly more diabetes-specific exams and tests after enrollment (3.8 vs
      6.4, P <.001) than patients not enrolled in the program (3.5 vs 3.6, P <.001).
      Patients in the intervention group had an average of 2 more physician visits for
      diabetes than those in the comparison group (P <.001). Conversely, the
      intervention group had fewer diabetes-related hospitalizations (-0.027, P =
      .003). Patients in the intervention group incurred higher expenses due to
      physician visits but lower expenses due to inpatient services, with a net
      increase of $104 per person per year (P <.001). CONCLUSIONS: This P4P program for
      diabetes was associated with a significant increase in regular follow-up visits
      and evidence-based services, and significantly lower hospitalization costs. The
      overall cost of care for those in the P4P program was significantly higher,
      although the total incremental expense was quite small.

PMID- 20148608
TI  - Effect of physician-specific pay-for-performance incentives in a large group
      practice.
AB  - OBJECTIVE: To assess the effect of a physician-specific pay-for-performance
      program on quality-of-care measures in a large group practice. STUDY DESIGN: In
      2007, Palo Alto Medical Clinic, a multispecialty physician group practice,
      changed from group-focused to physician-specific pay-for-performance incentives.
      Primary care physicians received incentive payments based on their quarterly
      assessed performance. METHODS: We examined 9 reported and incentivized clinical
      outcome and process measures. Five reported and nonincentivized measures were
      used for comparison purposes. The quality score of each physician for each
      measure was the main dependent variable and was calculated as follows: Quality
      Score = (Patients Meeting Target / Eligible Patients) x 100. Differences in
      scores between 2006 and 2007 were compared with differences in scores between
      2005 and 2006. We also compared the performance of Palo Alto Medical Clinic with
      that of 2 other affiliated physician groups implementing group-level incentives.
      RESULTS: Eight of 9 reported and incentivized measures showed significant
      improvement in 2007 compared with 2006. Three measures showed an improvement
      trend significantly better than the previous year's trend. A similar improvement
      trend was observed in 1 related measure that was reported but was
      nonincentivized. However, the improvement trend of Palo Alto Medical Clinic was
      not consistently different from that of the other 2 physician groups.
      CONCLUSIONS: Small financial incentives (maximum, $5000/year) based on individual
      physicians' performance may have led to continued or enhanced improvement in well
      established ambulatory care measures. Compared with other quality improvement
      programs having alternative foci for incentives (eg, increasing support for staff
      hours), the effect of physician-specific incentives was not evident.

PMID- 20148609
TI  - Medication adherence and enrollment in a consumer-driven health plan.
AB  - OBJECTIVE: To evaluate the impact of enrolling in a consumer-driven health plan
      (CDHP) on adherence to maintenance drugs. STUDY DESIGN: Two-year retrospective
      cohort study. METHODS: Consumer-driven health plan patients were enrolled in a
      traditional managed care plan in 2005 (pre-year) and a full-replacement CDHP in
      2006 (post-year). Traditional-plan patients voluntarily enrolled in a traditional
      plan in both years. Adherence measures included (1) post-year continuation rate
      among continuous users, (2) time to refill the first prescription in the post
      year, (3) change in the compliance rate from the pre- to the post-year, and (4)
      total days with continuous drug supply in the post-year. Analysis was conducted
      on 8 drug classes. RESULTS: The CDHP patients had a slightly higher illness
      burden and used more medication in the pre-year. The continuation rate was
      relatively high for all drug classes, although the CDHP cohort had a lower
      probability of continuing cardiac and cholesterol drugs. Consumer-driven health
      plan patients took slightly longer on average to refill their first prescription
      in the post-year for cardiac, hypertension, cholesterol, and thyroid drugs. The
      compliance rate dropped over time in both cohorts, but the reduction was bigger
      among CDHP patients for 3 drug classes (adjusted ratio of the odds ratios was
      0.77, 0.78, and 0.69 for asthma, cardiac, and cholesterol drugs, respectively).
      The CDHP patients also terminated their continuous drug supply 21 days earlier
      for epilepsy drugs and 27 days earlier for cholesterol drugs. CONCLUSIONS:
      Adherence was lower for a few drug classes among CDHP patients.

PMID- 20148610
TI  - Case study of linking dental and medical healthcare records.
AB  - OBJECTIVE: To link the administrative data of a large dental carrier and an
      integrated health plan in Washington State to conduct an observational study of
      diabetes and periodontal disease. STUDY DESIGN: Evaluation of variable
      suitability, testing of linkage variables, and performing an n - 1 deterministic
      linkage strategy. METHODS: We examined a variety of administrative data variables
      for their consistency over time and their information richness to use as matching
      variables. After choosing social security number, date of birth, first name, and
      last name, we tested their reliability as linking variables among a population
      with dual dental and medical insurance. Lastly, we performed four n - 1
      deterministic linkage steps to obtain our study population. RESULTS: With a
      success match rate of more than 96% with the 4 test variables, we extracted the
      entire population who met the study criteria with the understanding that only a
      subset would successfully link. We linked 78,230 individuals (55.2% of the Group
      Health Cooperative population). Of these matches more than 50% occurred within a
      last name-first name-birth date deterministic match. CONCLUSIONS: Employer groups
      who provide dental-medical benefits for their employees send identical
      administrative data to dental and healthcare plans. The n - 1 deterministic
      linkage was accomplished by using a relatively straightforward approach because
      these data were fairly homogeneous and of high quality. Until medical care and
      dental care are integrated, it is possible to link these data to assess the
      impact of oral disease on overall health.

PMID- 20148611
TI  - Predialysis nephrology care among older veterans using Department of Veterans
      Affairs or Medicare-covered services.
AB  - OBJECTIVE: To examine the effect of exclusive and dual use of Department of
      Veterans Affairs (VA) and Medicare healthcare systems on outpatient predialysis
      nephrology care. STUDY DESIGN: Retrospective cohort study. METHODS: Receipt,
      timeliness, and intensity of predialysis nephrology care were evaluated among
      8033 veterans who initiated dialysis in 2000 and 2001 and were eligible for both
      VA and Medicare coverage in the 12 months preceding dialysis initiation.
      Propensity scores were incorporated into analyses to minimize potential selection
      bias from nonrandom veteran allocation to healthcare systems. RESULTS: Among the
      cohort, 17.4% were users of VA services only (VA-only users), 38.5% were users of
      Medicare-covered services only (Medicare-only users), and 44.1% were users of
      both VA and Medicare-covered services (dual users). Sixty-six percent of VA-only
      and dual users and 58.1% of Medicare-only users received predialysis nephrology
      care. Compared with Medicare-only users, dual users were more likely (risk ratio
      [RR], 1.12; 95% confidence interval [CI], 1.07-1.17) and VA-only users were as
      likely (RR, 0.98; 95% CI, 0.88-1.08) to have received predialysis nephrology
      care. Compared with Medicare-only use, VA-only use (RR, 0.63; 95% CI, 0.50-0.81)
      and dual use (RR, 0.78; 95% CI, 0.70-0.88) were associated with a lower
      likelihood of late nephrology care (<3 months before dialysis initiation).
      CONCLUSIONS: More than one-third of older veterans initiating dialysis do not
      receive nephrology care beforehand. Dual use of VA and Medicare-covered services
      was associated with greater receipt and favorable timeliness of predialysis
      nephrology care, while use of only Medicare-covered services was associated with
      late predialysis nephrology care. Further studies to identify reasons for system
      level variations in access to predialysis nephrology care may assist in
      identifying opportunities for improvement.

PMID- 20148612
TI  - Thinking clearly about payment reform.

PMID- 20148613
TI  - Tiered networks: strategies of engagement for patients and physicians.

PMID- 20148614
TI  - Effects of electronic decision support on high-tech diagnostic imaging orders and
      patients.
AB  - OBJECTIVE: To evaluate the effects of providing appropriateness criteria through
      guideline-based electronic health record (EHR) decision support for high-tech
      diagnostic imaging (HTDI) procedures. STUDY DESIGN: Chart audits were performed
      on a random sample of adult primary care orders for 3 HTDI procedures (computed
      tomography [CT] and magnetic resonance imaging [MRI] of the head, and MRI of the
      lumbar spine) before and after implementation of an EHR decision support system.
      OUTCOME MEASURES: Level of appropriateness, abnormal findings, and apparent
      effects on patient care. RESULTS: A total of 299 eligible audits were performed.
      Decision support was associated with a 20% to 36% drop in spine MRI and head CT
      orders, but head MRI order volume was unaffected. Combined results for the 3
      procedures showed that a larger proportion of studies ordered after implementing
      decision support (89.2% vs 79.5%, P = .02) fit appropriateness criteria, and more
      postimplementation studies had A ratings (highest utility rating) (81.8% vs 70%,
      P = .04). However, there were no differences in the proportion of tests with
      positive findings (42/132 vs 28/120, P = .16 among procedures that met definite
      criteria) or the proportion with a likely impact on patients (6.6% vs 10.8%, P =
      .07). CONCLUSIONS: These data support the feasibility of using chart audits to
      assess the relationship between appropriateness criteria and HTDI orders.
      Although introduction of EHR clinical decision support for diagnostic imaging
      orders was associated with reduced volume and increased appropriateness of
      orders, there was little apparent impact on either findings or patients.

PMID- 20148615
TI  - Subacute lack of asthma control as a predictor of subsequent acute asthma
      exacerbation in a managed care population.
AB  - OBJECTIVE: To evaluate whether an assessment of subacute lack of asthma control
      (SALAC) predicts subsequent acute asthma exacerbation (AAE). STUDY DESIGN: This
      retrospective administrative claims study used medical and pharmacy claims from
      the HealthCore Integrated Research Database to identify patients aged 6 to 64
      years with asthma and having 3 years' continuous enrollment from January 1, 2003,
      through December 31, 2005. METHODS: Study inclusion criteria were at least 2
      outpatient visits or at least 1 hospitalization or emergency department (ED)
      visit with an asthma diagnosis (International Classification of Diseases, Ninth
      Revision, Clinical Modification code 493.xx) in at least 1 of 3 years (2003
      2005). SALAC was defined as more than 4 asthma outpatient visits or more than 5
      short-acting beta2-agonist (SABA) prescriptions per year, and AAE was defined as
      at least 1 hospitalization or ED visit with a primary asthma diagnosis or an oral
      corticosteroid burst prescription. Generalized estimating equations modeled the
      risk of subsequent-year AAE as a function of 2 sets of variables to determine the
      independent effect of prior-year SALAC and its components on subsequent-year AAE.
      The first set included age, sex, geographic region, prior year AAE, and prior
      year SALAC. The second set included age, sex, geographic region, prior-year AAE,
      high prior-year SABA use, and frequent prior-year asthma outpatient visits.
      RESULTS: Of 35,806 patients with asthma, 46.6% were male, and 35.8% were younger
      than 18 years. The mean annual prevalence of SALAC was 12.1%. Controlling for all
      other variables, the generalized estimating equation results indicate that prior
      year SALAC is associated with a 60% increased risk of subsequent-year AAE (P
      <.001). Increased prior-year asthma outpatient visits and SABA use are associated
      with 34% and 85%, respectively, greater risks of subsequent-year AAE (P <.001 for
      both). CONCLUSION: SALAC and its components can aid in predicting patients at
      risk for AAE.

PMID- 20148616
TI  - Pattern of statin use among 10 cohorts of new users from 1995 to 2004: a register
      based nationwide study.
AB  - OBJECTIVE: To analyze differences in the pattern of statin use among 10
      consecutive yearly cohorts of new users in Finland. STUDY DESIGN: Retrospective
      cohort study based on administrative claims data. METHODS: New users of statins
      from January 1, 1995, to December 31, 2004, were captured from a nationwide
      prescription register, and the pattern of statin use was observed until December
      31, 2005. The association between year of statin initiation and persistence with
      statin therapy during the first year of statin use was modeled using Cox
      proportional hazards regression analysis with multivariable adjustment. The
      median adherence (proportion of days covered) was computed among patients who
      discontinued therapy during each 365-day interval since statin initiation.
      RESULTS: In total, 490,024 new users of statins were identified. In the
      multivariable-adjusted model, discontinuation during the first year among
      initiators of statin use in 1996 and 1997 was similar to that in 1995 (hazard
      ratio [HR], 0.99; 95% confidence interval [CI], 0.95-1.03 in 1996; and HR, 1.01;
      95% CI, 0.98-1.05 in 1997). Compared with the 1995 cohort, the 1998, 1999, 2000,
      2001, 2002, 2003, and 2004 cohorts were less likely to discontinue statin use.
      Hazard ratios of discontinuation for the cohorts ranged from 0.91 (95% CI, 0.88
      0.94) in 1998 to 0.80 (95% CI, 0.78-0.83) in 2004. There were no differences in
      adherence with respect to the duration of therapy among the yearly cohorts.
      CONCLUSIONS: Compared with the 1995 cohort, 1-year persistence with statin
      therapy in Finland improved among new users of statins in 1998, and the
      improvement persisted up to 2004. Adherence to statin therapy remained stable
      among initiators from 1995 to 2004.

PMID- 20148617
TI  - Consumer experience with a tiered physician network: early evidence.
AB  - OBJECTIVE: To analyze consumer awareness, use, and trust of a tiered provider
      network, which differentiates copayments by provider cost-efficiency and quality.
      STUDY DESIGN: Mail survey of a plan-stratified random sample of individuals in
      health plans offered by the Massachusetts Group Insurance Commission. METHODS:
      Pearson's chi2 tests and multinomial logistic regression were used to analyze the
      effect of demographics and other characteristics on consumer awareness,
      understanding, trust, and use of a tiered provider network. RESULTS: Half (49.5%)
      of respondents reported prior knowledge of the tiered networks in their health
      plan. Whites, respondents who saw a specialist in the last year, and respondents
      who used the Internet for health information were more likely to be aware of the
      tiers. A majority of respondents either did not trust (35.5%) or did not know
      whether they trusted (22.5%) the tiers to tell them which physicians were better
      than others. Nineteen percent of respondents reported knowing which tier one of
      their physicians was in; of this group, 50.1% learned this information at or
      after their first visit. Respondents who learned their physician's tier before
      the first visit were more likely to find this information important to their
      decision to see that physician (60.5% vs 39.5%; P <.01). CONCLUSIONS: These
      findings suggest use of tiered networks to direct consumers to preferred
      providers requires increased consumer awareness and trust in the health plan as a
      source for provider rankings. Efforts targeting consumers before they decide to
      see a physician may be more successful.

PMID- 20148619
TI  - Improving patient self-management of multiple sclerosis through a disease therapy
      management program.
AB  - OBJECTIVE: To examine the effect of a multiple sclerosis (MS) disease therapy
      management (DTM) program that incorporates a disease self-management component
      and a medication therapy management component within a structured 7-month
      program. STUDY DESIGN: Observational cohort study. METHODS: Pharmacy claims were
      evaluated over an 8-month follow-up period to calculate injectable MS medication
      adherence and persistence among 156 continuously eligible patients who completed
      the DTM program compared with 156 patients in each of 2 propensity score-matched
      control groups (retail pharmacy patients and specialty pharmacy patients). For
      283 patients completing the DTM program, the Short Form 12, Work Productivity
      Activity Impairment questionnaire, and MS relapses were assessed at month 0 and
      at month 6. RESULTS: Injectable MS medication adherence was significantly higher
      for DTM patients compared with retail pharmacy patients (0.92 vs 0.86, P <.001)
      and was similar for DTM patients and specialty pharmacy patients (0.92 vs 0.90, P
      = .23). The DTM patients demonstrated significantly greater persistence on
      therapy (220 days) compared with the specialty pharmacy patients (188 days) (P =
      .002) and the retail pharmacy patients (177 days) (P <.01). The Short Form 12 and
      Work Productivity Activity Impairment results did not significantly change from
      month 0 to month 6. Multiple sclerosis relapses were reported by 14.0% of
      patients at month 0 and by 9.3% of patients at month 6 (P = .03). Ninety-seven
      percent of patients at month 6 reported that the DTM program was very helpful or
      somewhat helpful in enabling them to better manage their health. CONCLUSIONS: An
      MS DTM program incorporating medication management resulted in increased
      adherence and persistence to injectable MS medications and decreased MS relapses.
      Quality of life and work productivity were not significantly changed. Patients
      reported improved ability to manage their health.

PMID- 20148618
TI  - Geographic correlation between large-firm commercial spending and Medicare
      spending.
AB  - OBJECTIVE: To investigate the correlation between geographic variation in
      inpatient days, total spending, and spending growth in traditional Medicare
      versus the large-firm commercial sector. STUDY DESIGN: Retrospective descriptive
      analysis. METHODS: Medicare spending data at the hospital referral region (HRR)
      level were obtained from the Dartmouth Atlas. Commercial claims data from large
      employers were obtained from Thomson Reuters MarketScan Database for 1996-2006
      and aggregated to the HRR level. County-level data on inpatient days per capita
      and market characteristics were obtained from the Area Resource File. We computed
      correlations between Medicare and commercial spending and spending growth, as
      well as Medicare and non-Medicare inpatient days, and examined traits of high-
      and low-spending HRRs in both sectors. RESULTS: We found a positive correlation
      between inpatient days per capita across counties, but a small inverse
      correlation between measures of commercial and Medicare spending across HRRs.
      Spending growth was weakly positively correlated across HRRs. Markets in the
      upper third of commercial spending had more concentrated hospital markets than
      markets in the lower third of commercial spending. The reverse was true for
      Medicare spending. CONCLUSIONS: The positive correlation in utilization and lack
      of correlation in spending implies an inverse correlation in prices. This is
      consistent with evidence that the differences appear to be, at least partially,
      related to aspects of the market structure. If private markets are to work better
      to reduce cost, stronger efforts are needed to reduce provider market
      concentration and promote competitive pricing for healthcare services.

PMID- 20148620
TI  - Interprofessional education and collaborative practice.

PMID- 20148621
TI  - Determinants of the need for homophily in referral criteria: the case of clergy
      referrals to mental health professionals in Singapore.
AB  - Homophily, the tendency to seek out those who are similar, is a powerful force in
      structuring the relations that people have in a variety of social settings
      including the selection of partnerships. Despite this, attitudinal homophily has
      seldom been discussed in relation to referral practices, an important
      consideration in health care delivery. In this paper Christian clergy in
      Singapore are examined as to the extent they impose homophily as a selection
      criteria for referrals to mental health professionals. This is an important
      consideration as clergy are popular sources of help though they seldom refer
      their clients to mental health professionals due to the competition between
      health sectors. This study based on survey data collected from a representative
      sample of Singaporean clergymen predicts that those who expect referral partners
      to be homophilous include those with greater Christian conservatism, professional
      ideology and beliefs in clergy competence in handling emotional and mental
      problems. These ministers tended to come from smaller congregations and had more
      psychological education. In essence clergy who value homophily in referral
      partners are concerned about the relational risk involved in the referral process
      and use homophily in the hope that they can find referral partners who do not
      undermine their authority or jeopardize laymen's faith.

PMID- 20148622
TI  - Interprofessional education in US medical schools.

PMID- 20148627
TI  - Nanogels in the race for drug delivery.

PMID- 20148626
TI  - Microscale oral delivery devices incorporating nanoparticles.

PMID- 20148628
TI  - Multifunctional radionanomedicine: a novel nanoplatform for cancer imaging and
      therapy.

PMID- 20148630
TI  - Conference Scene: NanoBiotech Montreux 2009.

PMID- 20148632
TI  - Beta-cyclodextrin-centered star-shaped amphiphilic polymers for doxorubicin
      delivery.
AB  - AIM: Delivery of doxorubicin could be achieved by a novel micellar system based
      on beta-cyclodextrin-centered star-shaped amphiphilic polymers (sPEL/CD). This
      study specifically explored the effect of polylactide segments in sPEL/CD on
      various micelle properties, such as the critical micelle concentration, size,
      drug loading, cytotoxicity and drug resistance reversing effect. METHOD: The
      sPEL/CD was synthesized by the arm-first method. The critical micelle
      concentrations of polymeric micelles were determined by fluorescence
      spectrophotometry using pyrene as a probe. The oil/water method was applied to
      prepare doxorubicin-loaded micelles. 3-(4,5-dimethylthi-azol-2-yl)-2,5
      diphenyltetrazolium bromide, confocal laser-scanning microscopy and flow
      cytometry were used to examine cell cytotoxicity and cellular uptake of the
      doxorubicin-loaded micelles. Finally, rhodamine-123 cellular uptake was
      determined to evaluate the polymer action on MCF-7 and MCF-7/ADR cells. RESULTS:
      All polymers exhibited low cytotoxicity and their micelles had a desirable
      release-acceleration pH (pH 5.0) for cytoplasmic drug delivery. With the
      introduction of polylactide into the polymer, the micelle critical micelle
      concentration can be effectively decreased and the drug-loading content was
      enhanced. Most importantly, the drug resistance of MCF-7/ADR cells was
      significantly reversed via the interaction between polymer and Pgp. Therefore,
      this type of polymer has potential superiority for cancer therapy.

PMID- 20148631
TI  - Conjugation of bevacizumab to cationic liposomes enhances their tumor-targeting
      potential.
AB  - AIMS: Cationic liposomes have been shown to preferentially target the tumor
      vasculature, but not uniformly. Bevacizumab antibody selectively accumulates in
      tumors expressing VEGF. We thus developed bevacizumab-modified, pegylated
      cationic liposomes (PCLs) to improve the distribution of liposomes along tumor
      vessels, and to enhance tumor targeting. MATERIALS & METHODS: We evaluated the
      delivery vehicle both in the absence and presence of VEGF, using human pancreatic
      cancer (Capan-1, HPAF-II and PANC-1) and endothelial (MS1-VEGF and HMEC-1) cell
      lines. RESULTS: All cell lines except for HMEC-1 secreted VEGF. Modification of
      PCLs with bevacizumab did not alter zeta-potential, but increased overall
      liposome size. The toxicity profile for bevacizumab-modified PCLs was cell line
      dependent and, in general, bevacizumab improved cellular uptake and tumor
      targeting of PCLs. CONCLUSION: Bevacizumab-modified PCLs represent a potential
      improvement over the unmodified variety, supporting their future development for
      the treatment of cancer.

PMID- 20148633
TI  - Micro-Raman study of the role of sterilization on carbon nanotubes for biomedical
      applications.
AB  - AIM: We investigate the effect of four different types of sterilization
      procedures on the structural properties and morphological features of single-wall
      carbon nanotube samples approachable by micro-Raman spectroscopy. Sterilization
      procedures (treatment in humid heat autoclave or ethylene oxide and irradiation
      with gamma-rays or UV light) are necessary in view of the use of carbon nanotube
      sterile samples in in vivo toxicity tests on laboratory rats. Micro-Raman
      spectroscopy allows us to estimate several details about the morphology of the
      single-wall carbon nanotube mixture (mainly the presence of disorder and diameter
      distribution) before and after the sterilization treatment. RESULTS: The best of
      these treatments, in other words, the one that least affected the morphology and
      structural properties of carbon nanotubes, was found to be UV irradiation and has
      thus been selected for future in vivo tests on rats.

PMID- 20148634
TI  - Enhancement of magnetic nanoparticle-mediated gene transfer to astrocytes by
      'magnetofection': effects of static and oscillating fields.
AB  - AIMS: To assess the feasibility of using magnetic nanoparticles (MNPs) to
      transfect astrocytes derived for transplantation and determine if transfection
      efficacy can be enhanced by static and oscillating magnetic fields. METHODS:
      Astrocytes were transfected using MNPs functionalized with a plasmid encoding a
      reporter protein. Transfection efficacies were compared following application of
      static fields and a novel, oscillating array system at a range of frequencies.
      The transplantation potential of transfected cells was tested in organotypic
      cerebellar slice cultures. RESULTS: Rat astrocytes can be efficiently transfected
      using MNPs with applied static/oscillating fields; the latter effect is frequency
      dependent. Transfected astrocytes could survive and differentiate following
      introduction into 3D neural tissue arrays. CONCLUSION: MNP vectors can safely and
      effectively transfect rodent astrocytes and could form the basis of a
      'multifunctional nanoplatform' for neural cell transplantation.

PMID- 20148635
TI  - Synthesis and characterization of luminescent cerium oxide nanoparticles.
AB  - AIMS: Fluorescent cerium oxide (ceria) nanoparticles were developed through
      incorporation of erbium into the lattice. Catalytic properties and luminescent
      behavior are examined. MATERIALS & METHODS: Cerium-erbium mixed oxide
      nanoparticles were synthesized by the reverse micelles route. Purity, size, and
      composition were characterized. Catalytic properties were measured using a
      hydrogen peroxide assay, and the luminescence properties were determined by
      confocal microscopy. RESULTS: The nanoparticles exhibited enhancement of the
      catalytic properties with increasing erbium content to 10 mole% in the cerium
      oxide lattice; and they demonstrated emission at 515 nm and 572.5 nm under 405 nm
      UV excitation in aqueous conditions. CONCLUSION: Erbium incorporation into ceria
      based nanoparticles were developed, having catalytic properties similar to and
      better than purely synthesized ceria and luminescent properties under UV
      irradiation by confocal microscopy.

PMID- 20148636
TI  - New pegylated polyaspartamide-based polyplexes as gene delivery vectors.
AB  - AIMS: To synthesize novel polyhydroxyethylaspartamide (PHEA) copolymers
      containing spermine (Spm) and polyethylene glycol (PEG) moieties in high yields,
      with the expectation that this material would show stealth properties and the
      ability to complex DNA by electrostatic interactions. MATERIALS & METHODS: PHEA
      PEG-Spm copolymer was prepared with a two-step reaction. Chemical,
      physicochemical and biological characterizations of PHEA-PEG-Spm copolymers and
      their obtained polyplexes with pDNA were performed. RESULTS: The introduction of
      spermine in PHEA structure allows to obtain a copolymer bearing in the side
      chains polyamine moieties capable to interact with DNA. On the other hand, the
      introduction of PEG in polymeric structure increased the DNA condensing ability
      of PHEA-PEG-Spm copolymer in comparison with the derivatives without PEG (PHEA
      Spm), and improved its characteristics of biocompatibility. CONCLUSIONS: PHEA-PEG
      Spm copolymer shows excellent ability to complex and condense plasmidic DNA
      giving interpolyelectrolyte complexes to act as gene delivery systems. Moreover,
      PEGylation confers to the obtained interpolyelectrolyte complexes stealth
      properties.

PMID- 20148637
TI  - Protein nanodisk assembling and intracellular trafficking powered by an arginine
      rich (R9) peptide.
AB  - AIMS: Arginine(R)-rich cationic peptides are powerful tools in drug delivery
      since, alone or when associated with polyplexes, proteins or chemicals, they
      confer DNA condensation, membrane translocation and blood-brain barrier crossing
      abilities. The unusual stability and high in vivo performance of their associated
      drugs suggest a particulate organization or R(n) complexes, which this study
      aimed to explore. MATERIALS & METHODS: We have analyzed the particulate
      organization and biological performance in DNA delivery of a model, R9-containing
      green fluorescent protein by dynamic light scattering, transmission electron
      microscopy, atomic force microscopy, single cell confocal microscopy and flow
      cytometry. RESULTS: A deep nanoscale examination of R9-powered constructs reveals
      a novel and promising feature of R9, that when fused to a scaffold green
      fluorescent protein, promote its efficient self-assembling as highly stable,
      regular disk-shaped nanoparticles of 20 x 3 nm. These constructs are efficiently
      internalized in mammalian cells and rapidly migrate through the cytoplasm towards
      the nucleus in a fully bioactive form. Besides, such particulate platforms
      accommodate, condense and deliver plasmid DNA to the nucleus and promote plasmid
      driven transgene expression. CONCLUSION: The architectonic properties of arginine
      rich peptides at the nanoscale reveal a new category of protein nanoparticles,
      namely nanodisks, and provide novel strategic concepts and architectonic tools
      for the tailored construction of new-generation artificial viruses for gene
      therapy and drug delivery.

PMID- 20148639
TI  - Biopharmaceutical parameters to consider in order to alter the fate of
      nanocarriers after oral delivery.
AB  - Oral route is the most common route for the delivery of drugs because it is
      simple to implement and improves patient compliance and quality of life. However,
      oral absorption is limited by various physiological barriers and remains a
      scientific challenge. Nanometric-sized drug delivery systems are being
      extensively studied and provide promising potential for oral drug delivery. Many
      different technological solutions have been proposed to enhance the
      bioavailability or the targeting of drug after oral administration. To reach
      these goals, it is important to analyze the biopharmaceutical parameters to
      consider in order to alter the fate of nanocarriers after oral delivery. In the
      present review, the gastrointestinal barrier and physiological stress factors
      with regard to nanocarriers' performance or integrity issues are first described.
      Second, the different characteristics offered by the nanocarriers (size, surface
      composition and properties mediated by external factors such as ligands) and
      their effect on the optimal transport of drug into the bloodstream are discussed.
      Finally, the integrity issue is discussed in function of the expected role of the
      nanocarriers: bioavailability enhancement or pharmacological targeting.

PMID- 20148640
TI  - Fullerene-porphyrin nanostructures in photodynamic therapy.
AB  - Photodynamic therapy represents an alternative treatment with great potential in
      some types of cancer and premalignant conditions. In the quest to improve this
      therapy, potential new nontetrapyrrole photosensitizers are currently under
      research. Hence, in the last few years fullerenes attracted an increased interest
      because they prove characteristics for nanotechnology's biomedical applications.
      Fullerenes derivatization for biology application in general and in particular
      for photodynamic therapy, led to the idea of their association with porphyrins.
      Porphyrins, well-known players in this domain, could form in association with
      fullerenes, new compounds with unique properties, namely new photosensitizers
      with enhanced efficiency in terms of singlet oxygen generation and tumor cell
      penetration. This article is an attempt to underscore the enormous effort
      currently dedicated to an emerging field represented by these new nanostructures
      for biomedicine and in particular for photodynamic therapy.

PMID- 20148638
TI  - Emerging nanotechnology approaches for HIV/AIDS treatment and prevention.
AB  - Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination
      antiretroviral therapy has dramatically improved treatment, but it has to be
      taken for a lifetime, has major side effects and is ineffective in patients in
      whom the virus develops resistance. Nanotechnology is an emerging
      multidisciplinary field that is revolutionizing medicine in the 21st century. It
      has a vast potential to radically advance the treatment and prevention of
      HIV/AIDS. In this review, we discuss the challenges with the current treatment of
      the disease and shed light on the remarkable potential of nanotechnology to
      provide more effective treatment and prevention for HIV/AIDS by advancing
      antiretroviral therapy, gene therapy, immunotherapy, vaccinology and
      microbicides.

PMID- 20148641
TI  - DNA-incorporating nanomaterials in biotechnological applications.
AB  - The recently developed ability to controllably connect biological and inorganic
      objects on a molecular scale opens a new page in biomimetic methods with
      potential applications in biodetection, tissue engineering, targeted therapeutics
      and drug/gene delivery. Particularly in the biodetection arena, a rapid
      development of new platforms has largely been stimulated by a spectrum of novel
      nanomaterials with physical properties that offer efficient, sensitive and
      inexpensive molecular sensing. Recently, DNA-functionalized nano-objects have
      emerged as a new class of nanomaterials that can be controllably assembled in
      predesigned structures. Such DNA-based nanoscale structures might provide a new
      detection paradigm due to their regulated optical, electrical and magnetic
      responses, chemical heterogeneity and high local biomolecular concentration. The
      specific biorecognition DNA and its physical-chemical characteristics allows for
      an exploitation of DNA-functionalized nanomaterials for sensing of nucleic acids,
      while a broad tunability of DNA interactions permits extending their use for
      detection of proteins, small molecules and ions. We discuss the progress that was
      achieved in the last decade in the exploration of new detection methods based on
      DNA-incorporating nanomaterials as well as their applications to gene delivery.
      The comparison between various detection platforms, their sensitivity and
      selectivity, and specific applications are reviewed.

PMID- 20148644
TI  - Fiber intake and endometrial cancer risk.
AB  - BACKGROUND: The epidemiological evidence on the relation between dietary fiber
      intake and endometrial cancer is contradictory. Consequently, a case-control
      study was carried out to further investigate the role of dietary fiber intake in
      the etiology of endometrial cancer. MATERIAL AND METHODS: Cases were 454 women
      with incident, histologically confirmed, endometrial cancer admitted to major
      teaching and general hospitals. Controls were 908 women admitted for acute, non
      neoplastic conditions to the same hospital network. Information on diet was
      elicited using a validated food frequency questionnaire. RESULTS: Odds ratios
      (OR) and 95% confidence intervals (CI) for quintiles of various types of fiber
      were estimated after allowance for total energy intake and other potential
      confounding factors. Lignin intake was significantly inversely related to
      endometrial cancer (OR=0.6 for the highest versus the lowest quintile of intake;
      95%CI: 0.4-0.9) with a slightly significant linear trend in risk (p-value=0.04).
      DISCUSSION: Data suggest the potential importance of lignin in the prevention of
      endometrial cancer at Italian consumption levels.

PMID- 20148645
TI  - Follow-up after treatment for breast cancer: one strategy fits all? An
      investigation of patient preferences using a discrete choice experiment.
AB  - Clinical guidelines for the follow-up after breast cancer recommend frequent
      outpatient clinic visits to be examined for a possible recurrence or a second
      primary breast tumour, and to receive information and psychosocial support.
      However, needs and preferences for follow-up may differ between patients, raising
      the question whether the current 'one size fits all' approach is appropriate.
      This study explored patients' preferences for follow-up. Patients and methods. A
      discrete choice experiment survey with 16 choice tasks was filled out by 331
      breast cancer patients. Each choice task consisted of two hypothetical follow-up
      scenarios for the first year after treatment, described by levels of the
      following characteristics; attendance at an educational group programme,
      frequency of visits, waiting time, contact mode, and type of healthcare provider.
      Results. The healthcare provider and contact mode were the most important
      characteristics of follow-up to patients. The medical specialist was the most
      preferred to perform the follow-up, but a combination of the medical specialist
      and breast care nurse alternating was also acceptable to patients. Face-to-face
      contact was strongly preferred to telephone contact. Follow-up visits every three
      months were preferred over visits every four, six, or 12 months. Heterogeneity in
      preference between patients was strong, especially for the healthcare provider
      and attendance at an educational group programme. Age, education, and previous
      experience with follow-up characteristics influenced preferences, but treatment
      modality did not. Conclusion. The results of this study show that overall patient
      satisfaction would not differ significantly if patients have follow-up by medical
      specialist and breast care nurse alternating compared to follow-up by a medical
      specialist only. Furthermore, we found heterogeneity in preferences for most
      attributes, indicating that one strategy does not fit all. Individualised follow
      up seems to offer the potential for significant increases in patient
      satisfaction.

PMID- 20148646
TI  - Taurine protects against lung damage following limb ischemia reperfusion in the
      rat by attenuating endoplasmic reticulum stress-induced apoptosis.
AB  - BACKGROUND AND PURPOSE: CHOP is a C/EBP family transcription factor involved in
      endoplasmic reticulum (ER) stress-mediated apoptosis. Several studies have
      demonstrated that ischemia reperfusion results in apoptosis. Oxidative stress is
      central to ischemia reperfusion-induced apoptosis. Taurine protects against lung
      injury after limb ischemia reperfusion (LIR) through antioxidation. The effects
      of taurine on ER stress-induced apoptosis have not been well explored, however.
      We studied the effects of taurine in ER stress-induced apoptosis following LIR.
      METHODS: Adult male Sprague-Dawley rats (n = 40) were randomized into 4 groups:
      (1) a control group, (2) an LIR group, (3) an LIR group treated with taurine, and
      (4) an LIR group treated with saline. Bilateral hindlimb ischemia was induced by
      application of a rubber band proximal to the level of the greater trochanters for
      4 h. The treatment groups received either taurine (200 mg/kg as a 4% solution in
      0.9% saline) or saline alone prior to reperfusion. Following 4h of reperfusion,
      blood oxygen was analyzed. The animals were killed and plasma and lung tissue
      were harvested for evaluation. RESULTS: Taurine statistically significantly
      attenuated lung injury following LIR, as shown by reduced malondialdehyde
      content, reduced cell apoptosis, and expression of activating transcription
      factor 4 (ATF4), X-box binding protein 1 (XBP1), and transcriptional activators
      of the CHOP gene. Furthermore, partial pressure values of oxygen in arterial
      blood and the activities of superoxide dismutase and catalase were higher in the
      taurine pretreatment group than in the group of rats that underwent LIR alone.
      INTERPRETATION: Our results suggest that taurine attenuates endoplasmic reticulum
      stress-induced apoptosis in the lungs of rats after limb ischemia reperfusion.

PMID- 20148647
TI  - Single-dose versus multiple-dose antibiotic prophylaxis for the surgical
      treatment of closed fractures.
AB  - BACKGROUND AND PURPOSE: Recent meta-analyses have suggested similar wound
      infection rates when using single- or multiple-dose antibiotic prophylaxis in the
      operative management of closed long bone fractures. In order to assist clinicians
      in choosing the optimal prophylaxis strategy, we performed a cost-effectiveness
      analysis comparing single- and multiple-dose prophylaxis. METHODS: A cost
      effectiveness analysis comparing the two prophylactic strategies was performed
      using time horizons of 60 days and 1 year. Infection probabilities, costs, and
      quality-adjusted life days (QALD) for each strategy were estimated from the
      literature. All costs were reported in 2007 US dollars. A base case analysis was
      performed for the surgical treatment of a closed ankle fracture. Sensitivity
      analysis was performed for all variables, including probabilistic sensitivity
      analysis using Monte Carlo simulation. RESULTS: Single-dose prophylaxis results
      in lower cost and a similar amount of quality-adjusted life days gained. The
      single-dose strategy had an average cost of $2,576 for an average gain of 272
      QALD. Multiple doses had an average cost of $2,596 for 272 QALD gained. These
      results are sensitive to the incidence of surgical site infection and deep wound
      infection for the single-dose treatment arm. Probabilistic sensitivity analysis
      using all model variables also demonstrated preference for the single-dose
      strategy. INTERPRETATION: Assuming similar infection rates between the
      prophylactic groups, our results suggest that single-dose prophylaxis is slightly
      more cost-effective than multiple-dose regimens for the treatment of closed
      fractures. Extensive sensitivity analysis demonstrates these results to be stable
      using published meta-analysis infection rates.

PMID- 20148648
TI  - Hematopoietic stem cells are coordinated by the molecular cues of the endosteal
      niche.
AB  - Hematopoietic stem cells (HSCs) accomplish a complex task. On a daily base
      billions of the 8 different mature cells are delivered in the right proportions.
      HSCs are located in niches located at several locations in the body.
      Communication between these spatially separated niches is accomplished by stem
      cells that leave their niche and migrate to other niches guided by soluble
      factors. The niche itself comprises all major signaling pathways (Hedgehog,
      Notch, Wnt, and BMP) and an array of adhesion molecules. The interplay between
      these components keep HSC in a quiescent state but also speed up production in
      case of urgent need during infection or excessive blood loss. In this review, we
      focus on the molecular cues of the niche, functional adhesion molecules and
      describe recent data obtained with multiphoton microscopy. A vast array of
      molecules is described that display similar functions as HSC controllers. This
      points to redundancy in the system that enables HSC to respond to different cues
      essentially with the same functional response. Apparently, the hematopoietic
      system is so crucial that it is not dependent on a single cue. When one cue fails
      to initiate a response, another cue will take over leading to an almost similar
      response. Another explanation is that every cue adds to an integrated signal that
      results in reaching the threshold. This integrated signal might be reached from
      huge signaling by a single cue or the low but additive signals by several cues.

PMID- 20148649
TI  - Characterization of mesenchymal stem cells isolated from the rabbit fetal liver.
AB  - Physiological attributes of mesenchymal stem cells (MSCs) including
      straightforward manipulation, multilineage differentiation, immunoregulation, and
      tropism for injury settings render them ideal therapeutic agents for tissue
      repair/regeneration. Nevertheless, further studies in suitable animal models of
      disease are needed to translate the potential of MSCs into clinical applications.
      We report here the isolation and preliminary characterization of MSCs from fetal
      rabbit liver (fl-MSCs). Compared with MSCs isolated from adult rabbit bone
      marrow, fl-MSCs had superior growth rate, clonogenic capability, and plastic
      adherence owing to their developmental immaturity. Both cytochemical staining and
      mRNA expression analysis of fl-MSCs confirmed mesodermal lineage differentiation
      into adipocytes, osteocytes, and chondrocytes. Moreover, fl-MSCs were capable to
      prevent lymphocyte proliferation both in a 2-way MLC and upon phytohemagglutinin
      (PHA) stimulation. In contrast, fl-MSCs co-cultured with allogeneic lymphocytes
      induced proliferation of the latter. Relatedly, although freshly isolated fl-MSCs
      did express neither major histocompatibility complex (MHC) class I/II nor
      CD80/CD86, all these immune synapse components were induced upon in vitro
      culture. Furthermore, fl-MSCs became efficiently transduced for long-term
      transgene expression with a retroviral vector. Thus, the special biological
      qualities of fl-MSCs endow them as model candidate vehicles/agents for gene/cell
      therapy strategies applied to a variety of rabbit models of injury, such as
      osteochondral lesions.

PMID- 20148650
TI  - Aqueous humor concentration of bevacizumab after subconjunctival injection in
      rabbit.
AB  - PURPOSE: To investigate whether bevacizumab may be delivered into the anterior
      chamber after subconjunctival administration and its pharmacokinetics in aqueous
      humor. METHODS: The right eye of 33 rabbits received subconjunctival injection of
      2.5 mg of subconjunctival bevacizumab. Three rabbits were sacrificed at each of
      the following time points: 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 h after the
      injection. Bevacizumab concentrations were measured in aqueous fluid of injected
      and uninjected eyes and serum using enzyme-linked immunosorbent assay. RESULTS:
      Bevacizumab was first detected in the aqueous humor of the injected eye at 12 h
      after the subconjunctival injection. A peak concentration of 70.59 +/- 26.01
      ng/mL was achieved at 36 h. Bevacizumab was also detected in the serum and
      aqueous humor of the uninjected contralateral eye. The concentration in the
      aqueous humor of the injected eye was lower than in the serum and higher than in
      the aqueous humor of the uninjected contralateral eye at all time points.
      Elimination of bevacizumab from the serum and aqueous humor of injected and
      uninjected eye paralleled with half-life of 57.78 +/- 13.75 h, 27.64 +/- 1.95 h
      and 28.05 +/- 2.55 h, respectively. CONCLUSIONS: We demonstrated that bevacizumab
      can be delivered into anterior chamber by single subconjunctival injection.
      Further study is needed to assess whether subconjunctival bevacizumab is
      clinically useful in patients with neovascular glaucoma.

PMID- 20148651
TI  - Lovastatin inhibits the thrombin-induced loss of barrier integrity in bovine
      corneal endothelium.
AB  - PURPOSE: Increased actomyosin contraction of the dense band of actin cytoskeleton
      at the apical junctional complex (perijunctional actomyosin ring, PAMR) breaks
      down the barrier integrity of corneal endothelium. This study has investigated
      the efficacy of statins, which inhibit activation of RhoA, in opposing the
      thrombin-induced loss of barrier integrity of monolayers of cultured bovine
      corneal endothelium. METHODS: Myosin light chain (MLC) phosphorylation, a
      biochemical measure of actomyosin contraction, was assayed by urea-glycerol gel
      electrophoresis, followed by western blot analysis. The locus of MLC
      phosphorylation and changes in the organization of the PAMR were visualized by
      immunostaining. Phosphorylation of MYPT1, a regulatory subunit of myosin light
      chain phosphatase (MLCP), was assessed by Western blot analysis to determine down
      regulation of RhoA. The barrier integrity was assessed in terms of trans
      endothelial electrical resistance (TER), and further confirmed by determining
      permeability to FITC dextran (10 kDa) and distribution of ZO-1, a marker of tight
      junctional assembly. RESULTS: Lovastatin, a prototype of lipophilic statins,
      induced MLC dephosphorylation under basal conditions. It opposed increase in
      phosphorylation of MLC and MYPT1 in response to thrombin and nocodazole, agents
      known to activate RhoA in the endothelium. Pretreatment with the statin opposed
      the thrombin- and nocodazole-induced disruption of the PAMR and the thrombin
      induced decline in TER. Lovastatin also opposed the thrombin- and nocodazole
      induced increase in permeability to FITC dextran and redistribution of ZO-1.
      However, upon supplementation with GGPP (geranylgeranyl pyrophosphate),
      lovastatin failed to oppose the effects of thrombin and nocodazole on the PAMR,
      ppMLC, and ZO-1 distribution. CONCLUSIONS: Lovastatin attenuates RhoA activation
      in the corneal endothelium presumably by reducing its isoprenylation. This
      underlies the suppression of the thrombin-induced loss in barrier integrity of
      the corneal endothelium.

PMID- 20148652
TI  - Ocular safety of infliximab in rabbit and cell culture models.
AB  - PURPOSE: To undertake the safety testing of infliximab in animal and cell culture
      models. METHODS: Sixteen New Zealand albino rabbits were divided into 4 groups of
      4 animals. Each group received 2 mg of infliximab in the right eye and saline
      solution in the left eye. Clinical examination and retinal histology were
      performed at months 1, 2, and 3 for groups A, B, and C, respectively.
      Electroretinography (ERG) recordings were made before the injection, and at
      months 1 and 2 for group D. The assessment of the safety of infliximab in retinal
      pigment epithelial (RPE) and retinal ganglion (RGC-5) cells was performed by
      Western blot analysis of caspase-3 involved in apoptosis pathway, the analysis of
      cytotoxicity of infliximab by WST-1 proliferation assay, and time-lapse video
      microscopy to register the morphology of treated cells in time-lapse. RESULTS:
      Clinical examination of the eyes, histological study of the retina, and ERG
      recordings showed no sign of ocular toxicity after a single intravitreal
      injection of 2 mg of infliximab in the rabbit model. RPE and RGC viability was
      not reduced either in the range of concentration (up to 3 mg) or during the
      follow-up interval. CONCLUSION: This study suggests that infliximab has no direct
      retinal toxicity using rabbit (2 mg) and cell culture (2 and 3 mg) models.

PMID- 20148653
TI  - Copolymer-1 immunization reduces damage in retinal ganglion cells under high
      intraocular pressure through altering the expression of retinal neurotrophins.
AB  - PURPOSE: To evaluate expression changes in retina neurotrophic factors (NTs) in
      glaucomatous rats with copolymer-1 (COP-1) immunization. METHODS: Three
      episcleral veins in rat eyes were cauterized to produce chronic high intraocular
      pressure (IOP). Qualified rats were divided into 3 groups: glaucoma group, COP-1
      immunization group, and PBS control group. Using immunohistochemistry and RT-PCR,
      we compared the expression of retinal NTs in these 3 groups. RESULTS: NGF, BDNF,
      and NT-4 expression increased to different degrees and the levels of their RNAs
      had transient increases under elevated IOP, but there were no statistical
      differences with respect to the RNAs of interest in the COP-1 immunization group
      compared with the 2 control groups. Expression of NT-3 appeared earlier and
      stronger in the rats immunized with COP-1 than in rats with glaucoma. Moreover,
      the expression of the COP-1 receptor, TrkC, increased accordingly. CONCLUSIONS:
      COP-1 immunization might increase NT-3 expression by some unknown mechanism in
      high IOP rats and the change may be related to COP-1 therapeutic intervention.

PMID- 20148654
TI  - Adjunctive intravitreal bevacizumab-combined trabeculectomy versus trabeculectomy
      alone in the treatment of neovascular glaucoma.
AB  - PURPOSE: To evaluate the effect of adjunctive intravitreal bevacizumab (ivBe)
      with trabeculectomy versus trabeculectomy alone in the management of patients
      with neovascular glaucoma (NVG). METHODS: Retrospective, consecutive,
      interventional case series. NVG patients were divided into groups by treatment:
      with adjunctive ivBe and trabeculectomy (ivBe group, n = 14 eyes) and with
      trabeculectomy only (control group, n = 28 eyes). The main outcome measure was
      visual acuity. Regression of iris neovascularization (NVI), change(s) in
      intraocular pressure (IOP), NVI recurrence, additional glaucoma surgeries
      required, eyes of leading to total blindness, intraoperative and postoperative
      complications, and number of topical medications required after trabeculectomy
      were regarded as second outcome measures. In the ivBe group, intravitreal
      injections of 2.5 mg bevacizumab were delivered using a sharp 27-gauge needle
      through the inferotemporal quadrant. RESULTS: Of 42 eyes of 42 patients
      identified, change in IOP, additional glaucoma surgeries required, and number of
      IOP-lowering topical medications required after trabeculectomy did not differ
      significantly between groups (P > 0.05 for all). However, the ivBe group had
      significantly higher frequency and rapidity of iris neovascular regression,
      improved visual acuity in the logarithm of minimum angle of resolution (logMAR),
      leading to total blindness in fewer eyes and intraoperative and postoperative
      complications in others than in the control group (P = 0.015, 0.002, 0.007,
      0.023, and 0.008, respectively). The follow-up duration (mean +/- SD) from
      trabeculectomy surgery was 179 +/- 97 days (range, 93-315 days) and 196 +/- 108
      days (range, 92-370 days) in the ivBe and control group (P = 0.324). CONCLUSIONS:
      Intravitreal bevacizumab might be a useful adjunctive therapy in addition to
      trabeculectomy in the management of NVG. Large controlled randomized studies for
      treatment of bevacizumab on NVG are warranted.

PMID- 20148656
TI  - A phase II study on the duration and stability of the intraocular pressure
      lowering effect and tolerability of Tafluprost compared with latanoprost.
AB  - PURPOSE: Tafluprost is a novel prostaglandin F(2alpha)-receptor agonist shown to
      lower intraocular pressure (IOP) in healthy humans and patients with elevated
      IOP. We investigated the efficacy, safety, and tolerability of tafluprost 0.0015%
      compared with latanoprost 0.005% in patients with primary open-angle glaucoma,
      exfoliation glaucoma, or ocular hypertension. METHODS: This was a randomized,
      double-masked, active-controlled, parallel-group, multinational, and multicenter
      phase II study. Patients received either tafluprost 0.0015% (n = 19) or
      latanoprost 0.005% (n = 19), both once daily. The extent and duration of action
      of the IOP-lowering effects at Day 42 and Day 43 were the primary efficacy
      endpoints. Efficacy and safety parameters were analyzed throughout. RESULTS:
      Maximum IOP reduction was achieved by Day 7 and was sustained until Day 42 in
      both groups (mean [standard deviation] change from baseline -9.7 [3.3] mm Hg for
      tafluprost and -8.8 [4.3] mm Hg for latanoprost). The overall treatment group
      difference was 0.17 mm Hg (95% confidence interval -1.27 to 1.61; P = 0.811). The
      IOP-lowering effect was maintained for >or=24 h after the last dose in both
      groups. Most adverse events were ocular and were similar in frequency and
      severity between groups. There were 3 severe adverse events, all ocular, and all
      in the tafluprost group (3/19 = 16%). CONCLUSIONS: Tafluprost and latanoprost
      have comparable effects on the extent, duration, and stability of IOP reduction,
      and are well tolerated in patients.

PMID- 20148655
TI  - Sustained subconjunctival protein delivery using a thermosetting gel delivery
      system.
AB  - PURPOSE: An effective treatment modality for posterior eye diseases would provide
      prolonged delivery of therapeutic agents, including macromolecules, to eye
      tissues using a safe and minimally invasive method. The goal of this study was to
      assess the ability of a thermosetting gel to deliver a fluorescently labeled
      protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a
      single subconjunctival injection of the gel. Additional experiments were
      performed to compare in vitro to in vivo ovalbumin release rates from the gel.
      METHODS: The ovalbumin content of the eye tissues was monitored by
      spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from
      dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days.
      At the same time points, fluorescence microscopy images of tissue samples were
      also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis
      of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37
      degrees C PBS solutions from ovalbumin-loaded gel pellets was also monitored over
      time by spectrophotometric assay. In vivo ovalbumin release rates were determined
      by measurement of residual ovalbumin extracted from gel pellets removed from rat
      eyes at various time intervals. RESULTS: Our results indicate that ovalbumin
      concentrations can be maintained at measurable levels in the sclera, choroid, and
      retina of rats for up to 14 days using the thermosetting gel delivery system. The
      concentration of ovalbumin exhibited a gradient that decreased from sclera to
      choroid and to retina. The in vitro release rate profiles were similar to the in
      vivo release profiles. CONCLUSIONS: Our findings suggest that the thermosetting
      gel system may be a feasible method for safe and convenient sustained delivery of
      proteins to choroidal and retinal tissue in the posterior segments of the eye.

PMID- 20148658
TI  - Photodynamic therapy with or without intravitreal triamcinolone acetonide for
      symptomatic polypoidal choroidal vasculopathy.
AB  - PURPOSE: To evaluate the outcome of verteporfin photodynamic therapy (PDT) with
      or without intravitreal triamcinolone acetonide (IVTA) for the treatment of
      symptomatic polypoidal choroidal vasculopathy (PCV). METHODS: Retrospective
      analysis of PCV patients who underwent PDT with or without IVTA with follow-up of
      2 or more years. Changes in best-corrected visual acuity (BCVA), proportion of
      eyes with moderate visual loss (3 or more lines), and complications were compared
      between patients with or without IVTA. RESULTS: Twenty-seven eyes of 27 patients
      were analyzed, with 12 eyes treated by PDT monotherapy and 15 eyes treated by
      combined PDT with IVTA. The baseline characteristics of both groups were similar.
      At 1 year, the mean logMAR BCVA for the PDT monotherapy group improved from 0.74
      to 0.58 (P = 0.011), whereas the combined PDT and IVTA group improved from 0.84
      to 0.74 (P = 0.17). At 2 years, the mean logMAR BCVA for the monotherapy and
      combined treatment groups were 0.62 and 0.84, respectively, and the changes
      compared with baseline were not statistically significant. No significant
      difference was found in the mean logMAR BCVA, the mean line of visual changes,
      and the mean number of PDT treatments between the 2 groups at 1 and 2 years. One
      (8.3%) and 4 (26.7%) eyes in the monotherapy and the combined groups lost 3 or
      more lines at 2 years, respectively. Patients who had combined PDT with IVTA were
      more likely to develop cataract requiring surgery and ocular hypertension (P =
      0.043 and 0.046, respectively). CONCLUSIONS: PDT reduced the risks of visual loss
      in patients with symptomatic PCV in the short term but the effect might not be
      sustained after 1 year. The adjunctive use of IVTA during PDT did not appear to
      result in additional benefit for treating PCV.

PMID- 20148657
TI  - Use of 5-Fluorouracil injections to reduce the risk of trabeculectomy bleb
      failure after cataract surgery.
AB  - PURPOSE: To determine whether the use of postoperative subconjunctival 5
      fluorouracil (5-FU) reduces the risk of trabeculectomy bleb failure after
      uncomplicated small incisional cataract surgery. METHODS: Twenty-five consecutive
      patients with primary open-angle glaucoma and a functioning trabeculectomy bleb
      and who underwent uncomplicated phacoemulsification surgery were given
      subconjunctival injections of 5 mg 5-FU at 2, 4, and 12 weeks after cataract
      surgery (5-FU group). The mean postoperative intraocular pressure (IOP) over a 2
      year period and the trabeculectomy survival rate, as determined by Kaplan-Meier
      survival analysis, was compared with a historical series of patients who had
      undergone cataract surgery in the presence of a filtering trabeculectomy bleb,
      but who had not received 5-FU (control group). RESULTS: After a 2-year follow-up
      period, there was no significant difference in the mean IOP between the 5-FU
      (15.1 mm Hg SD 3.1) and control (15.3 mm Hg SD 3.3) groups (P = 0.67). An IOP >
      21 mm Hg at any time point after the first postoperative month after cataract
      surgery was found in 4.0% cases in the 5-FU group and 16.7% cases in the control
      group (P = 0.78). Using Kaplan-Meier survival analysis, the difference in the
      cumulative probability of survival between the 5-FU and control groups was not
      significant (P = 0.30). CONCLUSION: Cataract surgery is a significant risk factor
      for trabeculectomy bleb failure. The use of subconjunctival 5-FU injections at 2,
      4, and 12 weeks after cataract surgery in elderly white patients with primary
      open-angle glaucoma does not reduce the risk of trabeculectomy failure.

PMID- 20148659
TI  - Novel nanoparticulate gel formulations of steroids for the treatment of macular
      edema.
AB  - PURPOSE: This article describes the development and characterization of PLGA
      nanoparticles of dexamethasone (DEX), hydrocortisone acetate (HA), and
      prednisolone acetate (PA) suspended in thermosensitive gels indicated for the
      treatment of macular edema (ME). METHODS: Nanoparticles were prepared by oil-in
      water (O/W) emulsion and dialysis methods using PLGA 50:50 and PLGA 65:35. These
      particles were characterized for entrapment efficiency, size distribution,
      surface morphology, crystallinity, and in vitro release. Further, ex vivo
      permeation studies of DEX in suspension and nanoparticulate formulations were
      carried out across the rabbit sclera. RESULTS: Entrapment efficiencies of DEX,
      HA, and PA were found to be lower with the dialysis method. O/W emulsion/solvent
      evaporation technique resulted in higher entrapment efficiencies, that is, 77.3%,
      91.3%, 92.3% for DEX, HA, and PA, respectively. Release from nanoparticles
      suspended in thermosensitive gels followed zero-order kinetics with no apparent
      burst effect. Ex vivo permeability studies further confirmed sustained release of
      DEX from nanoparticles suspended in thermosensitive gels. CONCLUSIONS: These
      novel nanoparticulate systems containing particles suspended in thermosensitive
      gels may provide sustained retina/choroid delivery of steroids following
      episcleral administration.

PMID- 20148660
TI  - Morphine-induced ocular hypotension is modulated by nitric oxide and carbon
      monoxide: role of mu3 receptors.
AB  - PURPOSE: Recent findings generated from our laboratory have demonstrated the
      involvement of nitric oxide (NO) in morphine-induced reduction of intraocular
      pressure (IOP). The present study was designed to investigate the possible
      involvement of carbon monoxide (CO) in morphine-induced reduction of IOP and the
      role of mu(3) opioid receptors. METHODS: New Zealand rabbits were used in this
      study. They were pretreated with the nitric oxide synthase inhibitor Nomega-nitro
      L-arginine methyl ester (L-NAME, 1%, 30 microL), or an inhibitor of heme
      oxygenase (HO), zinc protoporphyrin-IX (ZnPP-IX; 0.1 mg/kg; i.v.). The same
      animals were then treated with morphine (100 microg/30 microL) with or without NO
      or CO donors administration, sodium nitroprusside (SNP) and
      tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), respectively. A separate set
      of animals were pretreated with the nonselective opioid receptor antagonist,
      naloxone (100 microg/30 microL), or the micro(3) opioid receptor inhibitor, L
      glutathione (GSH, 1%, 30 microL), in the presence of SNP or CORM-3 followed by
      morphine administration. IOP measurements were taken at different times after
      monolateral instillation of morphine. RESULTS: Morphine induced a significant
      decrease in IOP and pretreatment with ZnPP-IX or L-NAME significantly prevented
      this effect whereas administration of NO or CO donors amplified morphine-induced
      decrease in IOP. This effect was partially abrogated both by pretreatment with
      ZnPP-IX or L-NAME, and by pretreatment with naloxone and GSH suggesting that the
      decrease in IOP relies on exogenous NO and CO liberated from SNP and CORM-3,
      respectively. CONCLUSIONS: We conclude that the endogenous NO/CO system and
      micro(3) receptors contribute to morphine-induced ocular hypotension and that the
      reduction of IOP elicited by morphine can be augmented by exogenous NO and CO.

PMID- 20148661
TI  - Intravitreal bevacizumab (avastin) in the treatment of macular edema associated
      with perfused retinal vein occlusion.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab
      (Avastin) injection in patients with macular edema (ME) secondary to retinal vein
      occlusive diseases. METHODS: A prospective, interventional cases series study was
      conducted in patients with ME secondary to perfused retinal vein occlusions
      (RVOs), who were treated with intravitreal bevacizumab (2.5 mg per injection in a
      volume of 0.1 mL). Patients underwent complete ophthalmic evaluation, including
      Snellen visual acuity, optical coherence tomography (OCT), and fluorescein
      angiography (FA) at baseline, 1 month, and 3 months after the first injection and
      at the final visit. RESULTS: Twenty-five patients (25 eyes) received intravitreal
      bevacizumab injections. The mean follow-up time was 6.5 months. Mean Snellen
      visual acuity improved from 20/125 at baseline to 20/74 at 1 month, 20/69 at 3
      months, and 20/57 at the last follow-up (P < 0.01). Five of the 25 eyes (20%) had
      vision gain of >3 lines. The mean central 1 mm macular thickness was 422 microm
      at baseline and decreased to 263, 333, and 239 microm at 1 month, 3 months, and
      the last follow-up, respectively. Recurrent macular edema with a rebound increase
      of central retinal thickness was observed 3 months after the first injection, and
      improved after repeated bevacizumab injections. Patients received an average of 2
      injections (range 1-3). FA showed no evidence of increased nonperfusion avascular
      area. No adverse ocular or systemic events were observed following injections.
      CONCLUSIONS: The observed anatomic and visual acuity improvements after
      intravitreal bevacizumab injection demonstrate that bevacizumab is a useful
      adjunctive treatment for ME secondary to RVO without safety concerns in a short
      term. However, repeated injections are needed to maintain visual improvement.
      Long-term study is warranted to assess the long-term efficacy and safety.

PMID- 20148662
TI  - Long-term follow-up after multiple intravitreal bevacizumab injections for
      exudative age-related macular degeneration.
AB  - PURPOSE: To analyze the long-term effect of multiple intravitreal injections of
      bevacizumab as therapy of exudative age-related macular degeneration (AMD).
      METHODS: The retrospective clinical interventional case series study included 45
      patients (48 eyes) who received intravitreal injections of bevacizumab (1.5 mg)
      for treatment of exudative AMD and for whom the follow-up was >2 years. All
      patients received an initial series of 3 injections applied in intervals of 6-8
      weeks. Subsequent injections were given in intervals ranging between 2 and 6
      months. The mean number of all injections performed per eye was 8.6 +/- 2.5. The
      mean follow-up was 27.8 +/- 3.6 months. The main outcome parameters were best
      corrected visual acuity (BCVA) and foveal thickness measurements by optical
      coherence tomography (OCT). RESULTS: Mean BCVA improved from 0.62 +/- 0.30 LogMAR
      at baseline to 0.55 +/- 0.28 LogMAR (P = 0.03) at 1 month after the 3 initial
      injections. At the end of follow-up, BCVA decreased significantly (P = 0.02) to
      0.76 +/- 0.41 LogMAR. Bivariate correlation tests showed that the change in BCVA
      from baseline to the final examination at the end of follow-up was significantly
      associated only with the baseline BCVA (correlation coefficient r = 0.39, P =
      0.006). The height of the subretinal fluid reduced significantly (P = 0.004) at 1
      month after the 3 initial injections and remained so till the final follow-up (P
      = 0.01). CONCLUSIONS: Multiple intravitreal bevacizumab injections initially led
      to an improvement in visual acuity, finally, however, failed to stabilize visual
      acuity after a follow-up of >2 years.

PMID- 20148663
TI  - Prevention of oxidative damage to lens by caffeine.
AB  - PURPOSE: The primary objective of this study was to examine the possibility of
      inhibiting oxidative damage to the lens in vitro by caffeine. METHODS: Oxidative
      damage was inflicted by incubating mouse lenses in Tyrode medium containing 0.1
      mM Fe(8)Br(8), an iron complex soluble in aqueous medium. Parallel incubations
      were conducted in the presence of caffeine (5 mM). RESULTS: Lenses incubated in
      the medium containing Fe(8)Br(8) undergo oxidative stress, as evidenced by the
      inhibition of Na(+)-K(+) ATPase-driven rubidium transport and the loss of tissue
      glutathione and ATP. These effects were prevented in presence of caffeine. That
      the effects are due to the oxyradicals produced was ascertained further by
      parallel studies with Tempol (5 mM), a well-known scavenger of reactive oxygen
      species (ROS) with its activity being more pronounced with hydroxyl radicals as
      compared to other ROS. CONCLUSIONS: Caffeine was found to be effective in
      preventing oxidative stress to the lens induced by iron under ambient conditions.
      The protective effect is attributable to its ability to scavenge ROS,
      particularly the hydroxyl radical.

PMID- 20148664
TI  - Protein conformation-based disease: getting to the heart of the matter.

PMID- 20148665
TI  - Cell death in the pathogenesis of heart disease: mechanisms and significance.
AB  - Cell death was once viewed as unregulated. It is now clear that at least a
      portion of cell death is a regulated cell suicide process. This type of death can
      exhibit multiple morphologies. One of these, apoptosis, has long been recognized
      to be actively mediated, and many of its underlying mechanisms have been
      elucidated. Moreover, necrosis, the traditional example of unregulated cell
      death, is also regulated in some instances. Autophagy is usually a survival
      mechanism but can occur in association with cell death. Little is known, however,
      about how autophagic cells die. Apoptosis, necrosis, and autophagy occur in
      cardiac myocytes during myocardial infarction, ischemia/reperfusion, and heart
      failure. Pharmacological and genetic inhibition of apoptosis and necrosis lessens
      infarct size and improves cardiac function in these disorders. The roles of
      autophagy in ischemia/reperfusion and heart failure are unresolved. A better
      understanding of these processes and their interrelationships may allow for the
      development of novel therapies for the major heart syndromes.

PMID- 20148667
TI  - The cardiac mitochondrion: nexus of stress.
AB  - The emergence of mitochondria as critical regulators of cardiac myocyte survival
      and death has revolutionized the field of cardiac biology. Indeed, it is now well
      recognized that mitochondrial dysfunction plays a crucial role in the
      pathogenesis of multiple cardiac diseases. A panoply of mitochondrial
      proteins/complexes ranging from canonical apoptosis proteins such as Bcl2 and
      Bax, through the mitochondrial permeability transition pore, to ion channels such
      as mitochondrial K(ATP) channels and connexin-43 have now been implicated as
      critical regulators of cardiac cell death. The purpose of this review, therefore,
      is to focus on these mitochondrial mediators/inhibitors of cell death and to
      address the specific mechanisms that underlie their ability to influence cardiac
      pathology.

PMID- 20148666
TI  - Autophagy during cardiac stress: joys and frustrations of autophagy.
AB  - The study of autophagy has been transformed by the cloning of most genes in the
      pathway and the introduction of GFP-LC3 as a reporter to allow visual assessment
      of autophagy. The field of cardiac biology is not alone in attempting to
      understand the implications of autophagy. The purpose of this review is to
      address some of the controversies and conundrums associated with the evolving
      studies of autophagy in the heart. Autophagy is a cellular process involving a
      complex orchestration of regulatory gene products as well as machinery for
      assembly, selective targeting, and degradation of autophagosomes and their
      contents. Our understanding of the role of autophagy in human disease is rapidly
      evolving as investigators examine the process in different tissues and different
      pathophysiological contexts. In the field of heart disease, autophagy has been
      examined in the settings of ischemia and reperfusion, preconditioning, cardiac
      hypertrophy, and heart failure. This review addresses the role of autophagy in
      cardioprotection, the balance of catabolism and anabolism, the concept of
      mitochondrial quality control, and the implications of impaired autophagic flux
      or frustrated autophagy.

PMID- 20148669
TI  - Physiology and global climate change.

PMID- 20148670
TI  - Living in the now: physiological mechanisms to tolerate a rapidly changing
      environment.
AB  - Rising atmospheric carbon dioxide has resulted in scientific projections of
      changes in global temperatures, climate in general, and surface seawater
      chemistry. Although the consequences to ecosystems and communities of metazoans
      are only beginning to be revealed, a key to forecasting expected changes in
      animal communities is an understanding of species' vulnerability to a changing
      environment. For example, environmental stressors may affect a particular species
      by driving that organism outside a tolerance window, by altering the costs of
      metabolic processes under the new conditions, or by changing patterns of
      development and reproduction. Implicit in all these examples is the foundational
      understanding of physiological mechanisms and how a particular environmental
      driver (e.g., temperature and ocean acidification) will be transduced through the
      animal to alter tolerances and performance. In this review, we highlight examples
      of mechanisms, focusing on those underlying physiological plasticity, that
      operate in contemporary organisms as a means to consider physiological responses
      that are available to organisms in the future.

PMID- 20148671
TI  - Light, time, and the physiology of biotic response to rapid climate change in
      animals.
AB  - Examination of temperate and polar regions of Earth shows that the nonbiological
      world is exquisitely sensitive to the direct effects of temperature, whereas the
      biological world is largely organized by light. Herein, we discuss the use of day
      length by animals at physiological and genetic levels, beginning with a
      comparative experimental study that shows the preeminent role of light in
      determining fitness in seasonal environments. Typically, at seasonally
      appropriate times, light initiates a cascade of physiological events mediating
      the input and interpretation of day length to the output of specific hormones
      that ultimately determine whether animals prepare to develop, reproduce,
      hibernate, enter dormancy, or migrate. The mechanisms that form the basis of
      seasonal time keeping and their adjustment during climate change are reviewed at
      the physiological and genetic levels. Future avenues for research are proposed
      that span basic questions from how animals transition from dependency on tropical
      cues to temperate cues during range expansions, to more applied questions of
      species survival and conservation biology during periods of climatic stress.

PMID- 20148668
TI  - The FoxO family in cardiac function and dysfunction.
AB  - The Forkhead family of transcription factors mediates many aspects of physiology,
      including stress response, metabolism, commitment to apoptosis, and development.
      The Forkhead box subfamily O (FoxO) proteins have garnered particular interest
      due to their involvement in the modulation of cardiovascular biology. In this
      review, we discuss the mechanisms of FoxO regulation and outcomes of FoxO
      signaling under normal and pathological cardiovascular contexts.

PMID- 20148672
TI  - Locomotion in response to shifting climate zones: not so fast.
AB  - Although a species' locomotor capacity is suggestive of its ability to escape
      global climate change, such a suggestion is not necessarily straightforward.
      Species vary substantially in locomotor capacity, both ontogenetically and
      within/among populations, and much of this variation has a genetic basis.
      Accordingly, locomotor capacity can and does evolve rapidly, as selection
      experiments demonstrate. Importantly, even though this evolution of locomotor
      capacity may be rapid enough to escape changing climate, genetic correlations
      among traits (often due to pleiotropy) are such that successful or rapid
      dispersers are often limited in colonization or reproductive ability, which may
      be viewed as a trade-off. The nuanced assessment of this variation and evolution
      is reviewed for well-studied models: salmon, flying versus flightless insects,
      rodents undergoing experimental evolution, and metapopulations of butterflies.
      This work reveals how integration of physiology with population biology and
      functional genomics can be especially informative.

PMID- 20148673
TI  - Genomic analyses of hormone signaling and gene regulation.
AB  - Many cellular signaling pathways ultimately control specific patterns of gene
      expression in the nucleus through a variety of signal-regulated transcription
      factors (TFs), including nuclear hormone receptors (NRs). The advent of genomic
      technologies for examining signal-regulated transcriptional responses and TF
      binding on a genomic scale has dramatically increased our understanding of the
      cellular programs that control hormonal signaling and gene regulation. Studies of
      TFs, especially NRs, using genomic approaches have revealed novel and unexpected
      features of hormone-regulated transcription, and a global view is beginning to
      emerge. In this review, we discuss the genomic methodologies that have been
      applied to the study of hormone-regulated gene expression, the results that have
      been obtained from using them, and the future prospects for these approaches.
      Given the wealth of information about hormone-dependent gene regulation by NRs,
      we have focused this review on the knowledge gained from genomic studies of their
      function.

PMID- 20148674
TI  - Macrophages, inflammation, and insulin resistance.
AB  - Obesity induces an insulin-resistant state in adipose tissue, liver, and muscle
      and is a strong risk factor for the development of type 2 diabetes mellitus.
      Insulin resistance in the setting of obesity results from a combination of
      altered functions of insulin target cells and the accumulation of macrophages
      that secrete proinflammatory mediators. At the molecular level, insulin
      resistance is promoted by a transition in macrophage polarization from an
      alternative M2 activation state maintained by STAT6 and PPARs to a classical M1
      activation state driven by NF-kappaB, AP1, and other signal-dependent
      transcription factors that play crucial roles in innate immunity. Strategies
      focused on inhibiting the inflammation/insulin resistance axis that otherwise
      preserve essential innate immune functions may hold promise for therapeutic
      intervention.

PMID- 20148676
TI  - Apical recycling of the gastric parietal cell H,K-ATPase.
AB  - The gastric parietal cell was the first system where a regulated membrane
      recycling hypothesis was proposed as the principal means for moving molecular
      transporters between cellular compartments. Upon stimulation, massive membrane
      flow from an endosomal compartment of tubulovesicle membranes to the apical
      secretory surface places the ATP-driven pumps in position to secrete a solution
      of strong acid in collaboration with several other membrane transporters. This
      review focuses on the membrane recycling pathway and proteins that support the
      recruitment and redistribution of H,K-ATPase-rich membranes, including those
      involved in signal transduction, membrane targeting, docking, and fusing, in
      addition to the integral role of the actin cytoskeleton and its associated
      proteins in the process of membrane recycling. Although much of the evidence
      discussed here comes from parietal cell studies, other physiological transport
      systems, as well as less complex cellular and in vitro models, are examined and
      cited for generality of principle.

PMID- 20148677
TI  - Role of colonic short-chain fatty acid transport in diarrhea.
AB  - Short-chain fatty acids (SCFA) are the major anion in stool and are synthesized
      from nonabsorbed carbohydrate by the colonic microbiota. Nonabsorbed carbohydrate
      are not absorbed in the colon and induce an osmotically mediated diarrhea; in
      contrast, SCFA are absorbed by colonic epithelial cells and stimulate Na
      dependent fluid absorption via a cyclic AMP-independent process involving apical
      membrane Na-H, SCFA-HCO(3), and Cl-SCFA exchanges. SCFA production represents an
      adaptive process to conserve calories, fluid, and electrolytes. Inhibition of
      SCFA synthesis by antibiotics and administration of PEG, a substance that is not
      metabolized by colonic microbiota, both result in diarrhea. In contrast,
      increased production of SCFA as a result of providing starch that is relatively
      resistant to amylase digestion [so-called resistant starch (RS)] to oral
      rehydration solution (RS-ORS) improves the efficacy of ORS and represents an
      important approach to improve the effectiveness of ORS in the treatment of acute
      diarrhea in children under five years of age.

PMID- 20148675
TI  - Structural overview of the nuclear receptor superfamily: insights into physiology
      and therapeutics.
AB  - As ligand-regulated transcription factors, the nuclear hormone receptors are
      nearly ideal drug targets, with internal pockets that bind to hydrophobic, drug
      like molecules and well-characterized ligand-induced conformational changes that
      recruit transcriptional coregulators to promoter elements. Yet, due to the
      multitude of genes under the control of a single receptor, the major challenge
      has been the identification of ligands with gene-selective actions, impacting
      disease outcomes through a narrow subset of target genes and not across their
      entire gene-regulatory repertoire. Here, we summarize the concepts and work to
      date underlying the development of steroidal and nonsteroidal receptor ligands,
      including the use of crystal structures, high-throughput screens, and rational
      design approaches for finding useful therapeutic molecules. Difficulties in
      finding selective receptor modulators require a more complete understanding of
      receptor interdomain communications, posttranslational modifications, and
      receptor-protein interactions that could be exploited for target gene
      selectivity.

PMID- 20148678
TI  - The biogenesis of chylomicrons.
AB  - The absorption of dietary fat is of increasing concern given the rise of obesity
      not only in the United States but throughout the developed world. This review
      explores what happens to dietary fat within the enterocyte. Absorbed fatty acids
      and monoacylglycerols are required to be bound to intracellular proteins and/or
      to be rapidly converted to triacylglycerols to prevent cellular membrane
      disruption. The triacylglycerol produced at the level of the endoplasmic
      reticulum (ER) is either incorporated into prechylomicrons within the ER lumen or
      shunted to triacylglycerol storage pools. The prechylomicrons exit the ER in a
      specialized transport vesicle in the rate-limiting step in the intracellular
      transit of triacylglycerol across the enterocyte. The prechylomicrons are further
      processed in the Golgi and are transported to the basolateral membrane via a
      separate vesicular system for exocytosis into the intestinal lamina propria.
      Fatty acids and monoacylglycerols entering the enterocyte via the basolateral
      membrane are also incorporated into triacylglycerol, but the basolaterally
      entering lipid is much more likely to enter the triacylglycerol storage pool than
      the lipid entering via the apical membrane.

PMID- 20148680
TI  - Cellular maintenance and repair of the kidney.
AB  - The mammalian kidney is a highly complex organ that requires the precise
      structural arrangement of multiple cell types for effective function. The need to
      filter large volumes of plasma at the glomerulus followed by active reabsorption
      of nearly 99% of that filtrate by the tubules creates vulnerability in both
      compartments for cell injury. Thus maintenance of cell viability and replacement
      of those cells that are lost are essential for functional stability of the
      kidney. This review addresses our current understanding of how cells from the
      glomerular, tubular, and interstitial compartments arise during development and
      the manner in which they may be regenerated in the adult organ. In addition, we
      discuss the data regarding the role of organ-specific and bone marrow-derived
      stem and progenitor cells in the replacement/repair process, as well as the
      potential for ex vivo programming of stem cells toward a renal lineage.

PMID- 20148679
TI  - Integrated brain circuits: astrocytic networks modulate neuronal activity and
      behavior.
AB  - The past decade has seen an explosion of research on roles of neuron-astrocyte
      interactions in the control of brain function. We highlight recent studies
      performed on the tripartite synapse, the structure consisting of pre- and
      postsynaptic elements of the synapse and an associated astrocytic process.
      Astrocytes respond to neuronal activity and neurotransmitters, through the
      activation of metabotropic receptors, and can release the gliotransmitters ATP, d
      serine, and glutamate, which act on neurons. Astrocyte-derived ATP modulates
      synaptic transmission, either directly or through its metabolic product
      adenosine. d-serine modulates NMDA receptor function, whereas glia-derived
      glutamate can play important roles in relapse following withdrawal from drugs of
      abuse. Cell type-specific molecular genetics has allowed a new level of
      examination of the function of astrocytes in brain function and has revealed an
      important role of these glial cells that is mediated by adenosine accumulation in
      the control of sleep and in cognitive impairments that follow sleep deprivation.

PMID- 20148681
TI  - Intrarenal purinergic signaling in the control of renal tubular transport.
AB  - Renal tubular epithelial cells receive hormonal input that regulates volume and
      electrolyte homeostasis. In addition, numerous intrarenal, local signaling
      agonists have appeared on the stage of renal physiology. One such system is that
      of intrarenal purinergic signaling. This system involves all the elements
      necessary for agonist-mediated intercellular communication. ATP is released from
      epithelial cells, which activates P2 receptors in the apical and basolateral
      membrane and thereby modulates tubular transport. Termination of the signal is
      conducted via the breakdown of ATP to adenosine. Recent far-reaching advances
      indicate that ATP is often used as a local transmitter for classical sensory
      transduction. This transmission apparently also applies to sensory functions in
      the kidney. Locally released ATP is involved in sensing of renal tubular flow or
      in detecting the distal tubular load of NaCl at the macula densa. This review
      describes the relevant aspects of local, intrarenal purinergic signaling and
      outlines its integrative concepts.

PMID- 20148682
TI  - The physiological significance of the cardiotonic steroid/ouabain-binding site of
      the Na,K-ATPase.
AB  - The Na,K-ATPase is the membrane "pump" that generates the Na(+) and K(+)
      gradients across the plasma membrane that drives many physiological processes.
      This enzyme is highly sensitive to inhibition by cardiotonic steroids, most
      notably the digitalis/ouabain class of compounds, which have been used for
      centuries to treat congestive heart failure and arrhythmias. The amino acids that
      constitute the ouabain-binding site are highly conserved across the evolutionary
      spectrum. This could be fortuitous or could result from this site being conserved
      because it has an important biological function. New physiological approaches
      using genetically engineered mice are being used to define the biological
      significance of the "receptor function" of the Na,K-ATPase and its regulation by
      potential endogenous cardiotonic steroid-like compounds. These studies extend the
      reach of earlier studies involving the biochemical purification of endogenous
      regulatory ligands.

PMID- 20148684
TI  - It's not all smooth muscle: non-smooth-muscle elements in control of resistance
      to airflow.
AB  - To achieve gas exchange, inspired air must pass through an intricate and dynamic
      tracheobronchial tree. The tree offers resistance to airflow, and increased
      resistance is the most important functional change in lung disease. Numerous
      mechanisms contribute to increased resistance by causing airway narrowing,
      closure, occlusion, and/or obliteration. Although airway smooth muscle (ASM)
      contraction and shortening are an important cause of increased resistance, non
      ASM elements can also contribute. Nonmuscle elements can modify the amount of
      airway narrowing for any given level of ASM shortening and the amount of
      shortening for a given level of ASM activation. In this review, we outline the
      physiological basis for airflow resistance and describe how changes in the lung
      parenchyma, the airways, and their luminal contents can contribute to increased
      airflow resistance. A detailed understanding of the mechanisms and consequences
      of increased airway resistance is vital to our attempts to alleviate the enormous
      burden of suffering caused by obstructive lung diseases.

PMID- 20148683
TI  - Inducible innate resistance of lung epithelium to infection.
AB  - Most studies of innate immunity have focused on leukocytes such as neutrophils,
      macrophages, and natural killer cells. However, epithelial cells play key roles
      in innate defenses that include providing a mechanical barrier to microbial
      entry, signaling to leukocytes, and directly killing pathogens. Importantly, all
      these defenses are highly inducible in response to the sensing of microbial and
      host products. In healthy lungs, the level of innate immune epithelial function
      is low at baseline. This is indicated by low levels of spontaneous microbial
      killing and cytokine release, reflecting low constitutive stimulation in the
      nearly sterile lower respiratory tract when mucociliary clearance mechanisms are
      functioning effectively. This contrasts with the colon, where bacteria are
      continuously present and epithelial cells are constitutively activated. Although
      the surface area of the lungs presents a large target for microbial invasion,
      activated lung epithelial cells that are closely apposed to deposited pathogens
      are ideally positioned for microbial killing.

PMID- 20148685
TI  - Regulation of endothelial permeability via paracellular and transcellular
      transport pathways.
AB  - The endothelium functions as a semipermeable barrier regulating tissue fluid
      homeostasis and transmigration of leukocytes and providing essential nutrients
      across the vessel wall. Transport of plasma proteins and solutes across the
      endothelium involves two different routes: one transcellular, via caveolae
      mediated vesicular transport, and the other paracellular, through
      interendothelial junctions. The permeability of the endothelial barrier is an
      exquisitely regulated process in the resting state and in response to
      extracellular stimuli and mediators. The focus of this review is to provide a
      comprehensive overview of molecular and signaling mechanisms regulating
      endothelial barrier permeability with emphasis on the cross-talk between
      paracellular and transcellular transport pathways.

PMID- 20148686
TI  - TH17 cells in asthma and COPD.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) represent two classes of
      chronic obstructive lung disorders that may share some similar immunologic
      mechanisms of disease. Asthma is a complex human disease characterized by airway
      hyperresponsiveness (AHR) and inflammation, whereas COPD is marked by progressive
      emphysematic changes in the lung. Recently it has been shown that advanced COPD
      is characterized by lymphoid follicles, drawing attention to immunological
      mechanisms in COPD. Despite numerous studies in mice to elucidate the immunologic
      mechanisms of asthma, sufficient current treatment options are limited.
      Clinically, many asthma patients fail to satisfactorily respond to standard
      steroid therapy, and this type of steroid-resistant, severe asthma has been
      linked to the presence of neutrophilic inflammation in the lung. The role of
      neutrophils, macrophages, and their secreted proteases in COPD needs to be better
      defined. Recently, the T lymphocyte subset T(H)17 was shown to play a role in
      regulating neutrophilic and macrophage inflammation in the lung, suggesting a
      potential role for T(H)17 cells in severe, steroid-insensitive asthma and COPD.

PMID- 20148687
TI  - The mammalian circadian timing system: organization and coordination of central
      and peripheral clocks.
AB  - Most physiology and behavior of mammalian organisms follow daily oscillations.
      These rhythmic processes are governed by environmental cues (e.g., fluctuations
      in light intensity and temperature), an internal circadian timing system, and the
      interaction between this timekeeping system and environmental signals. In
      mammals, the circadian timekeeping system has a complex architecture, composed of
      a central pacemaker in the brain's suprachiasmatic nuclei (SCN) and subsidiary
      clocks in nearly every body cell. The central clock is synchronized to
      geophysical time mainly via photic cues perceived by the retina and transmitted
      by electrical signals to SCN neurons. In turn, the SCN influences circadian
      physiology and behavior via neuronal and humoral cues and via the synchronization
      of local oscillators that are operative in the cells of most organs and tissues.
      Thus, some of the SCN output pathways serve as input pathways for peripheral
      tissues. Here we discuss knowledge acquired during the past few years on the
      complex structure and function of the mammalian circadian timing system.

PMID- 20148689
TI  - Systems biology of mammalian circadian clocks.
AB  - Systems biology is a natural extension of molecular biology; it can be defined as
      biology after identification of key gene(s). Systems-biological research is a
      multistage process beginning with (a) the comprehensive identification and (b)
      quantitative analysis of individual system components and their networked
      interactions, which lead to the ability to (c) control existing systems toward
      the desired state and (d) design new ones based on an understanding of the
      underlying structure and dynamical principles. In this review, we use the
      mammalian circadian clock as a model system and describe the application of
      systems-biological approaches to fundamental problems in this model. This
      application has allowed the identification of transcriptional/posttranscriptional
      circuits, the discovery of a temperature-insensitive period-determining process,
      and the discovery of desynchronization of individual clock cells underlying the
      singularity behavior of mammalian clocks.

PMID- 20148688
TI  - Suprachiasmatic nucleus: cell autonomy and network properties.
AB  - The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals.
      Individual SCN neurons in dispersed culture can generate independent circadian
      oscillations of clock gene expression and neuronal firing. However, SCN
      rhythmicity depends on sufficient membrane depolarization and levels of
      intracellular calcium and cAMP. In the intact SCN, cellular oscillations are
      synchronized and reinforced by rhythmic synaptic input from other cells,
      resulting in a reproducible topographic pattern of distinct phases and amplitudes
      specified by SCN circuit organization. The SCN network synchronizes its component
      cellular oscillators, reinforces their oscillations, responds to light input by
      altering their phase distribution, increases their robustness to genetic
      perturbations, and enhances their precision. Thus, even though individual SCN
      neurons can be cell-autonomous circadian oscillators, neuronal network properties
      are integral to normal function of the SCN.

PMID- 20148691
TI  - Mammalian Per-Arnt-Sim proteins in environmental adaptation.
AB  - The Per-Arnt-Sim (PAS) domain is conserved across the kingdoms of life and found
      in an ever-growing list of proteins. This domain can bind to and sense endogenous
      or xenobiotic small molecules such as molecular oxygen, cellular metabolites, or
      polyaromatic hydrocarbons. Members of this family are often found in pathways
      that regulate responses to environmental change; in mammals these include the
      hypoxia, circadian, and dioxin response pathways. These pathways function in
      development and throughout life to regulate cellular, organ, and whole-organism
      adaptive responses. Remarkably, in the case of the clock, this adaptation
      includes anticipation of environmental change. In this review, we summarize the
      roles of PAS domain-containing proteins in mammals. We provide structural
      evidence that functionally classifies both known and unknown biological roles.
      Finally, we discuss the role of PAS proteins in anticipation of and adaptation to
      environmental change.

PMID- 20148692
TI  - Sequence-related off-target effect of Dz13 against human tumor cells and safety
      in adult and fetal mice following systemic administration.
AB  - The oligonucleotide Dz13, a DNA enzyme that cleaves c-Jun mRNA, is capable of
      inhibiting various model tumors in mice. However, to date, a thorough examination
      of its target specificity in tumor cells has not been performed. In addition, an
      evaluation of its safety in a mammalian whole organism system has not been
      carried out. Dz13 mutated oligonucleotides were designed and tested in a
      proliferation assay. Dz13 was also tested for its safety in vivo when
      administered intravenously in a bolus dose, or systemically in an in utero assay.
      While Dz13 down-regulated target gene (c-Jun) expression in human tumor cells, c
      Jun siRNA failed to cause cell growth inhibition. Furthermore, alteration of
      contiguous G motifs in Dz13 flanking arms inhibits cell death activity, but
      removal of the same from the catalytic core can increase cell death activity. A
      20mer (truncated) derivative Dz13 exhibited similar activity. Dz13 was not toxic
      to blood and solid tissues in adult or fetal mice, though slight hepatotoxicity
      was noted with histology. It was also void of adverse effects to the
      physiological processes of angiogenesis and apoptosis. Collectively, the data
      support the safety of Dz13 and its activity attributed to off-target effects.

PMID- 20148694
TI  - Growth of injected melanoma cells is suppressed by whole body exposure to
      specific spatial-temporal configurations of weak intensity magnetic fields.
AB  - PURPOSE: To measure the effect of exposure to a specific spatial-temporal,
      hysiologically-patterned electromagnetic field presented using different
      geometric configurations on the growth of experimental tumours in mice. METHODS:
      C57b male mice were inoculated subcutaneously with B16-BL6 melanoma cells in two
      blocks of experiments separated by six months (to control for the effects of
      geomagnetic field). The mice were exposed to the same time-varying
      electromagnetic field nightly for 3 h in one of six spatial configurations or two
      control conditions and tumour growth assessed. RESULTS: Mice exposed to the field
      that was rotated through the three spatial dimensions and through all three
      planes every 2 sec did not grow tumours after 38 days. However, the mice in the
      sham-field and reference controls showed massive tumours after 38 days. Tumour
      growth was also affected by the intensity of the field, with mice exposed to a
      weak intensity field (1-5 nT) forming smaller tumours than mice exposed to sham
      or stronger, high intensity (2-5 microT) fields. Immunochemistry of tumours from
      those mice exposed to the different intensity fields suggested that alterations
      in leukocyte infiltration or vascularisation could contribute to the differences
      in tumour growth. CONCLUSIONS: Exposure to specific spatial-temporal regulated
      electromagnetic field configurations had potent effects on the growth of
      experimental tumours in mice.

PMID- 20148693
TI  - Methicillin-resistant Staphylococcus aureus colonization or infection in Canada:
      National Surveillance and Changing Epidemiology, 1995-2007.
AB  - OBJECTIVE: To determine the incidence and describe the changing epidemiology of
      methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in
      Canadian hospitals from 1995-2007. SETTING: Forty-eight hospitals participating
      in the Canadian Nosocomial Infection Surveillance Program. DESIGN: Prospective,
      laboratory-based surveillance for incident cases of MRSA colonization or
      infection among hospitalized patients. METHODS: Clinical and epidemiologic data
      were obtained by review of hospital records. Standard criteria were used to
      determine whether MRSA colonization or infection was present and whether the MRSA
      strain was healthcare associated or community associated. A representative subset
      of isolates was characterized by use of pulsed-field gel electrophoresis and
      staphylococcal cassette chromosome (SCC) mec typing. RESULTS: From 1995 to 2007,
      a total of 37,169 hospitalized patients were newly identified as either infected
      or colonized with MRSA, and the overall incidence of both MRSA colonization and
      MRSA infection increased from 0.65 to 11.04 cases per 10,000 patient-days (P <
      .001). Of these 37,169 patients, 11,828 (32%) had an MRSA infection, and
      infection rate increased from 0.36 to 3.43 cases per 10,000 patient-days. The
      proportion of community-associated MRSA strains increased from 6% to 23% (P <
      .001). The most common genotype (47% of isolates) was CMRSA-2 (USA100/800); in
      2007, CMRSA-10 (USA300) was the second most common strain (27% of isolates),
      associated with SCCmec type IV. Patients with CMRSA-10 were predominantly from
      western Canada and were more likely to be children (odds ratio [OR], 10.0 [95%
      confidence interval {CI}, 7.4-13.4]) and to have infection (OR, 2.3 [95% CI, 1.9
      2.7]), especially skin and/or soft tissue infection (OR, 5.9 [95% CI, 5.0-6.9]).
      CONCLUSIONS: The overall incidence of both MRSA colonization and MRSA infection
      increased 17-fold in Canadian hospitals from 1995 to 2007. There has also been a
      dramatic increase in cases of community-associated MRSA infection due to the
      CMRSA-10 (USA300) clone. Continued surveillance is needed to monitor the ongoing
      evolution of MRSA colonization or infection in Canada and globally.

PMID- 20148695
TI  - Static magnetic field blood pressure buffering, baroreflex vs. vascular blood
      pressure control mechanism.
AB  - PURPOSE: We compared the effect of static magnetic field (SMF) and verapamil, a
      potent vascular calcium channel blocking agent, on sudden elevation in blood
      pressure in conjunction with arterial baroreflex sensitivity (BRS) and
      microcirculation. MATERIALS AND METHODS: Forty-four experiments were performed on
      conscious rabbits sedated using pentobarbital intravenous (i.v.) infusion (5 mg
      kg(-1) h(-1)). Mean femoral artery blood pressure (MAP), heart rate, BRS and ear
      lobe skin microcirculatory blood flow, estimated using microphotoelectric
      plethysmography (MPPG), were simultaneously measured after a 40 min exposure of
      the sinocarotid baroreceptors to 350 mT SMF, generated by Nd(2)-Fe(14)-B magnets,
      or 30 min of verapamil i.v. administration (20 microg kg(-1) min(-1)). BRS was
      assessed from heart rate and MAP responses to i.v. bolus of nitroprusside and
      phenylephrine. RESULTS: The decrease in phenylephrine-induced abrupt elevation in
      MAP (DeltaMAP(AE)) was significantly larger after verapamil than after SMF
      exposure. DeltaMAP(AE) inversely correlated with verapamil-induced significant
      increase in DeltaMPPG (r = 0.53, p < 0.000) and with SMF-induced significant
      increase in DeltaBRS (r = 0.47, p < 0.016). CONCLUSIONS: Our results suggest that
      verapamil-potentiated vascular blood pressure buffering mechanism was more
      effective than SMF-potentiated baroreflex-mediated blood pressure buffering
      mechanism, and a potential benefit of both approaches in cardiovascular
      conditions with abrupt high elevation in blood pressure.

PMID- 20148696
TI  - Lack of evidence for low-LET radiation induced bystander response in normal human
      fibroblasts and colon carcinoma cells.
AB  - PURPOSE: To investigate radiation-induced bystander responses and to determine
      the role of gap junction intercellular communication and the radiation
      environment in propagating this response. MATERIALS AND METHODS: We used medium
      transfer and targeted irradiation to examine radiation-induced bystander effects
      in primary human fibroblast (AG01522) and human colon carcinoma (RKO36) cells. We
      examined the effect of variables such as gap junction intercellular
      communication, linear energy transfer (LET), and the role of the radiation
      environment in non-targeted responses. Endpoints included clonogenic survival,
      micronucleus formation and foci formation at histone 2AX over doses ranging from
      10-100 cGy. RESULTS: The results showed no evidence of a low-LET radiation
      induced bystander response for the endpoints of clonogenic survival and induction
      of DNA damage. Nor did we see evidence of a high-LET, Fe ion radiation (1 GeV/n)
      induced bystander effect. However, direct comparison for 3.2 MeV alpha-particle
      exposures showed a statistically significant medium transfer bystander effect for
      this high-LET radiation. CONCLUSIONS: From our results, it is evident that there
      are many confounding factors influencing bystander responses as reported in the
      literature. Our observations reflect the inherent variability in biological
      systems and the difficulties in extrapolating from in vitro models to radiation
      risks in humans.

PMID- 20148690
TI  - Circadian organization of behavior and physiology in Drosophila.
AB  - Circadian clocks organize behavior and physiology to adapt to daily environmental
      cycles. Genetic approaches in the fruit fly, Drosophila melanogaster, have
      revealed widely conserved molecular gears of these 24-h timers. Yet much less is
      known about how these cell-autonomous clocks confer temporal information to
      modulate cellular functions. Here we discuss our current knowledge of circadian
      clock function in Drosophila, providing an overview of the molecular
      underpinnings of circadian clocks. We then describe the neural network important
      for circadian rhythms of locomotor activity, including how these molecular clocks
      might influence neuronal function. Finally, we address a range of behaviors and
      physiological systems regulated by circadian clocks, including discussion of
      specific peripheral oscillators and key molecular effectors where they have been
      described. These studies reveal a remarkable complexity to circadian pathways in
      this "simple" model organism.

PMID- 20148697
TI  - Lentivirus-mediated RNA interference of Ku70 to enhance radiosensitivity of human
      mammary epithelial cells.
AB  - PURPOSE: To investigate the radiosensitising effect of Ku autoantigen 70 (Ku70)
      and Ku autoantigen 80 (Ku80) knockdown by lentivirus-mediated RNA interference
      (RNAi) in the MCF10A immortalised human mammary epithelial cell line. MATERIALS
      AND METHODS: MCF10A cells were infected with lentiviral vectors for RNAi of Ku70.
      The Ku70-knockdown cell line (Ku70i) and a mock-infected control cell line
      (LVTHM) were used to perform radiation experiments. For the in vitro Micronucleus
      (MN) assay, both cell lines were irradiated with doses of 2 and 4 Gy (60)Co gamma
      rays. For cell survival experiments, doses ranging between 0 and 8 Gy were used.
      RESULTS: Western blot analysis showed that the Ku70 lentiviral vector was
      effective in silencing the expression of both Ku70 and Ku80. A significantly
      higher radiation-induced MN yield was obtained in the Ku70i cell line compared to
      the control LVTHM cell line. RNAi of Ku70 also resulted in a lower survival yield
      after irradiation compared to the control cell line. Analysis of cell death
      mechanisms showed that MCF10A cells (Ku70i and LVTHM) do not undergo apoptosis,
      but undergo post-irradiation cellular senescence. CONCLUSION: RNAi of Ku70
      resulted in increased chromosomal and cellular radiosensitivity in the MCF10A
      human mammary cell line after irradiation with (60)Co gamma-rays. These results
      further strengthen the role of the Ku protein in correct DNA double strand break
      (DSB) repair.

PMID- 20148698
TI  - Mutational effects of different LET radiations in rpsL transgenic Arabidopsis.
AB  - PURPOSE: In an effort to assess the characteristics of mutation induced by
      different linear energy transfer (LET) radiation in higher plants, the mutational
      effects of carbon-ion beams and gamma-rays were investigated in Arabidopsis.
      MATERIALS AND METHODS: The rpsL (Escherichia coli ribosomal protein small subunit
      S12) transgenic Arabidopsis (Arabidopsis/rpsL) mutation detection system was
      adopted. Dry seeds of Arabidopsis/rpsL were irradiated with gamma-rays and 208
      MeV carbon ions (208-MeV (12)C(5+)), and the mutation frequency and mutation
      spectrum were examined. RESULTS: The frequency of mutant clones increased
      following irradiation with 208-MeV (12)C(5+) and gamma-rays. Mutation spectrum
      analysis showed that G:C to A:T transitions and >2 bp deletions/insertions were
      significantly induced by both 208-MeV (12)C(5+) and gamma-rays. -1 and -2
      frameshift mutations were characteristic in the gamma-ray irradiated group.
      CONCLUSIONS: 208-MeV (12)C(5+) and gamma-rays induced different intragenic
      mutations in respect to the size of deletions, reflecting differences in the
      nature of the DNA damage induced. Our results also suggested that base
      substitutions derived from the generation of 8-oxoguanine were low in dry seeds.
      The mutation spectrum obtained in this study might have reflected the
      characteristic conditions of plant dry seeds such as low water content and cell
      proliferation activity.

PMID- 20148699
TI  - Irradiation induces regionally specific alterations in pro-inflammatory
      environments in rat brain.
AB  - PURPOSE: Pro-inflammatory environments in the brain have been implicated in the
      onset and progression of neurological disorders. In the present study, we
      investigate the hypothesis that brain irradiation induces regionally specific
      alterations in cytokine gene and protein expression. MATERIALS AND METHODS: Four
      month old F344 x BN rats received either whole brain irradiation with a single
      dose of 10 Gy gamma-rays or sham-irradiation, and were maintained for 4, 8, and
      24 h following irradiation. The mRNA and protein expression levels of pro
      inflammatory mediators were analysed by real-time reverse transcriptase
      polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA),
      and immunofluorescence staining. To elucidate the molecular mechanisms of
      irradiation-induced brain inflammation, effects of irradiation on the DNA-binding
      activity of pro-inflammatory transcription factors were also examined. RESULTS: A
      significant and marked up-regulation of mRNA and protein expression of pro
      inflammatory mediators, including tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), and monocyte chemoattractant protein-1 (MCP-1), was
      observed in hippocampal and cortical regions isolated from irradiated brain.
      Cytokine expression was regionally specific since TNF-alpha levels were
      significantly elevated in cortex compared to hippocampus (57% greater) and IL
      1beta levels were elevated in hippocampus compared to cortical samples (126%
      greater). Increases in cytokine levels also were observed after irradiation of
      mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays
      (EMSA) demonstrated that irradiation significantly increased activation of
      activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and cAMP response
      element-binding protein (CREB). CONCLUSION: The present study demonstrated that
      whole brain irradiation induces regionally specific pro-inflammatory environments
      through activation of AP-1, NF-kappaB, and CREB and overexpression of TNF-alpha,
      IL-1beta, and MCP-1 in rat brain and may contribute to unique pathways for the
      radiation-induced impairments in tissue function.

PMID- 20148700
TI  - Metalloporphyrin antioxidants ameliorate normal tissue radiation damage in rat
      brain.
AB  - PURPOSE: We examined the effects of manganese (III) meso-tetrakis (diethyl-2-5
      imidazole) porphyrin, a metalloporphyrin antioxidant (MPA), on neural tissue
      radiation toxicity in vivo and on tumour cell radiosensitivity in vitro.
      MATERIALS AND METHODS: MPA was administered directly into the right lateral
      ventricle of young adult, male Sprague-Dawley rats (0 or 3.4 microg) 3 h before
      treatment with a single fraction, 100 Gy radiation dose delivered to the left
      brain hemisphere. The effects of treatment on radiation responses were assessed
      at different time points following irradiation. RESULTS: MPA treatment prior to
      brain irradiation protected against acute radiation-induced apoptosis and
      ameliorated delayed damage to the blood-brain barrier and radiation necrosis, but
      without producing a discernible increase in tissue superoxide disumtase (SOD)
      activity. In vitro, MPA pretreatment protected against radiation-induced
      apoptosis in primary neuronal cultures and increased clonogenic survival of
      irradiated rat glioma C6 cells, but had no discernible effect on radiation
      induced DNA double-strand breaks. MPA, a low molecular weight SOD mimic,
      significantly increased mitochondrial SOD activity in C6 cells, but not total
      cellular SOD activity. MPA up-regulated C6 expression of heme-oxygenase 1 (HO-1),
      an endogenous radioprotectant, but had no effect on HO-1 levels in human
      astrocytoma U-251 cells, human prostatic carcinoma LNCaP cells, or primary rat
      brain microvascular endothelial cells in vitro, nor on brain tissue HO-1
      expression levels in vivo. CONCLUSIONS: Metalloporphyrin antioxidants merit
      further exploration as adjunctive radioprotectants for cranial
      radiotherapy/radiosurgery applications, although the potential for tumour
      protection must be carefully considered.

PMID- 20148701
TI  - Three endpoints of in vivo tumour radiobiology and their statistical estimation.
AB  - PURPOSE: To review the existing endpoints of tumour growth delay assays in
      experimental radiobiology with an emphasis on their efficient estimation for
      statistically significant identification of the treatment effect. To
      mathematically define doubling time (DT), tumour-growth delay (TGD) and cancer
      cell surviving fraction (SF) in vivo using exponential growth and regrowth models
      with tumour volume measurements obtained from animal experiments. MATERIALS AND
      METHODS: A statistical model-based approach is used to define and efficiently
      estimate the three endpoints of tumour therapy in experimental cancer research.
      RESULTS: The log scale is advocated for plotting the tumour volume data and the
      respective analysis. Therefore, the geometric mean should be used to display the
      mean tumour volume data, and the group comparison should be a t-test for the log
      volume to comply with the Gaussian-distribution assumption. The relationship
      between cancer-cell SF, TGD and rate of growth is rigorously established. The
      widespread formula for cell kill is corrected; it has been rigorously shown that
      TGD is the difference between DTs. The software for the tumour growth delay
      analysis based on the mixed modeling approach with a complete set of instructions
      and example can be found on the author's webpage. CONCLUSIONS: The existing
      practice for TGD data analysis from animal experiments suffers from imprecision
      and large standard errors that yield low power and statistically insignificant
      treatment effect. This practice should be replaced with a model-based statistical
      analysis on the log scale.

PMID- 20148704
TI  - Contribution of Chinese Pekin duck complement component C3d-P29 repeats to
      enhancement of Th2-biased immune responses against NDV F gene induced by DNA
      immunization.
AB  - BACKGROUND AND AIM: C3d, a split product of C3, interacts with its receptor (CR2
      or CD21) on B cells and follicular dendritic cells (FDCs) and is crucial for
      induction and maintenance of a normal humoral immune response. This fragment of
      complement protein C3 (C3d) has also been shown to enhance B cell responses when
      complexed with antigen and C3d fusion increased Th2-biased immune response by
      inducing IL-4 production. MATERIALS AND METHODS: The gene fragment coding for
      Chinese Pekin duck (Anas platyrhynchos) C3d gene (duC3d) was cloned and expressed
      as a component of fusion proteins destined for use in in vitro experiments. Two,
      four and six copies of CR2-binding domain duC3d-P29 were fused, respectively, to
      truncated Newcastle disease virus (NDV) F gene encoding soluble glycoprotein F in
      pcDNA3.1.All recombinant proteins were analyzed by SDS-PAGE and Western
      immunoblot. BALB/c mice were, respectively, immunized with recombinant plasmids,
      blank vector, and inactivated vaccine. RESULTS: The result of immunogenicity
      detections of The IL-4 level for F-C3d-P29.6 DNA immunization approached that for
      the inactivated vaccine. Compared to C3d-P29.6, C3d-P29.4 enhanced F DNA
      immunogenicity to a lesser extent. Furthermore, C3d-P29.n fusion increased Th2
      biased immune response by inducing IL-4 production. CONCLUSION: We demonstrated
      that C3d-P29 could enhance immunogenicity by directing Th1-biased to a balanced
      and more effective Th1/Th2 response. The expression of the duck C3d fusion
      proteins in this study which was the first reported, and the detections of the
      cytokine level for F-C3d-P29.n in DNA immunization using the BALB/c mice as the
      model animal, will provide the basis for immunization trials in chicken or other
      poultry, studies of receptor binding and cell activation of animal lymphocytes,
      and investigations of new types of vaccine, including genetic recombinant and DNA
      vaccines for the future against relevant pathogens.

PMID- 20148706
TI  - Cytotoxic effect of garlic extract and its fractions on Sk-mel3 melanoma cell
      line.
AB  - Cutaneous cancers are among the most common forms of cancer. Melanoma is an
      aggressive malignancy which is poor in prognosis. Despite of many years of
      researches, the treatment of melanoma is still a problem. Historically, plants
      have been main resources in traditional medicine and natural products are
      considered as important sources of antitumor drugs. Meanwhile, garlic for a long
      time has been used in man's food as a medicinal plant. In this study, the garlic
      extract was prepared and fractionated by ultra-filtration method with Amicon
      system. Garlic extract and its fractions including residue (R) 100, R50, R30,
      R10, R5, and filtrate (F) 5 were investigated for their cytotoxic activities on
      Sk-mel3 cell line of melanoma. The results show that garlic extract induced a
      significant cytotoxic activity on Sk-mel3 cell line. Among fractions R100 and R10
      have more potential in cytotoxic activities against Sk-mel3 melanoma cells. In
      conclusion, garlic appears to be a good candidate as an antitumor agent against
      melanoma. To clarify the effective molecules and their mechanisms more studies
      should be applied on animal models and humans.

PMID- 20148705
TI  - The effect of IL-28A on human cord blood CD4+ T cells.
AB  - BACKGROUND AND AIM: The utilization of umbilical cord blood transplantation
      (UCBT) has been increasing because of the potential advantage of rapid
      accessibility and the lesser risk of graft-versus-host disease (GVHD), thus
      allowing less strict HLA matching. IL-28A, also known as IFN-lambda2, has been
      regarded as a member of a new cytokine family that shares some features with type
      I interferon (IFN) and was shown to have antiviral activity. The aim of this
      study was to identify biological activity of IL-28 on cord blood CD4(+) T cells.
      MATERIALS AND METHODS: In this study, we cultured CD4(+) T cells with IL-28A (20
      ng/ml), IL-2 (20 ng/ml) and 5microg/ml MACS Anti-Biotin MACSiBead Particles (bead
      to-cell ratio 1:2) for 2 weeks. RESULTS: Flow cytometry analyses showed that IL
      28A cannot be effective on CD25 and Foxp3 expression on cord blood CD4(+) T
      cells, and it is not involved in proliferation of these cells. Treg suppression
      assay also showed that this cytokine cannot induce production of regulatory T
      cells. CONCLUSION: We showed that IL-28A is not involved in expression of CD25
      and Foxp3 markers and proliferation of CD4(+)CD25(-) T cells, and that our
      findings also suggest that induction of Foxp3 in T cells activated by anti
      CD3/anti-CD28 does not result in the regulatory activity in these cells.

PMID- 20148707
TI  - Isopranoid- and dipalmitoyl-aminophospholipid adjuvants impact differently on
      longevity of CTL immune responses.
AB  - The success of lipid membranes as cytotoxic T-cell (CTL) adjuvants requires
      targeted uptake by antigen-presenting cells (APCs) and delivery of the antigen
      cargo to the cytosol for processing. To target the phosphatidylserine (PS)
      receptor of APCs, we prepared antigen-loaded liposomes containing
      dipalmitoylphosphatidylserine and archaeal lipid liposomes (archaeosomes),
      containing an equivalent amount of archaetidylserine, and compared their ability
      to promote short and long-term CTL activity in animals. CTL responses were
      enhanced by the incorporation of PS into phosphatidylcholine/cholesterol
      liposomes and, to a lesser extent, into phosphatidylglycerol/cholesterol
      liposomes, that correlated to the amount of surface amino groups reactive with
      trinitrobenzoyl sulfonate. Archaeosomes contrasted to the liposome adjuvants by
      exhibiting higher amounts of surface amino groups and inducing superior shorter
      and, especially, longer-term CTL responses. The incorporation of dipalmitoyl
      lipids into archaeosomes induced instability and prevented long-term, but not
      short-term, CTL responses in mice. The importance of glycero-lipid cores
      (isopranoid versus dipalmitoyl) to the longevity of the CTL response achieved was
      shown further by incorporating dipalmitoyl phosphatidylethanolamine (DPPE) or
      equivalent amounts of synthetic archaetidylethanolamine (AE) into archaeosome
      adjuvants. Both DPPE and AE at equivalent (5 mol%) concentrations enhanced the
      rapidity of CTL responses in mice, indicating the importance of the head group in
      the short term. In the longer term, 5% of DPPE (but not 5% of AE) was
      detrimental. In addition to head-group effects critical to the potency of short
      term CTL responses, the longer term CTL adjuvant properties of archaeosomes may
      be ascribed to stability imparted by the archaeal isopranoid core lipids.

PMID- 20148708
TI  - Control of drug release by incorporation of sorbitol or mannitol in
      microcrystalline-cellulose-based pellets prepared by extrusion-spheronization.
AB  - Mixtures of microcrystalline cellulose (MCC) with sorbitol (up to 50%) or
      mannitol (up to 80%) were investigated as major excipients for controlled
      accelerated release of the model poorly water-soluble drug hydrochlorothiazide
      from pellets prepared by extrusion/spheronization. Optimal wetting volume
      decreased with increasing polyol content and was always less than the volume
      required for maximum wet mass consistency. All pellet formulations had
      satisfactory morphological, mechanical and flow properties, although sorbitol/MCC
      pellets were rougher than mannitol/MCC pellets. Together they presented a wide
      range of drug release profiles in 0.1 M HCl, allowing the rate of drug release
      into aqueous media to be controlled by manipulation of sorbitol or mannitol
      content. Pellets with a 50% sorbitol content released hydrochlorothiazide faster
      than pellets with a 50% mannitol content because of their greater porosity and
      the greater solubility of sorbitol in water. Fastest release was from pellets
      with an 80% mannitol content, which rapidly underwent complete disintegration.

PMID- 20148709
TI  - Galactosylated solid lipid nanoparticles with cucurbitacin B improves the liver
      targetability.
AB  - This study intended to prepare liver-targeting solid lipid nanoparticles (SLNs)
      with a hepatoprotective drug, cucurbitacin B (Cuc B), using a galactosylated
      lipid, N-hexadecyl lactobionamide (N-HLBA). The galactosyl-lipid N-HLBA was
      prepared via the lactone form intermediates of lactobionic acid and synthesized
      by anchoring galactose to hexadecylamine lipid. The Cuc B-loaded galactosylated
      and conventional SLNs were successfully prepared by a high-pressure
      homogenization method. The two SLNs showed similar physical and pharmaceutical
      properties, including: the particle size measured by laser diffraction was 135 nm
      for galactosylated SLN (GalSLN) and 123 nm for conventional SLNs (CSLN); zeta
      potentials were -31.6 mV (GalSLN) and -34.3 mV(CSLN); in vitro release behavior
      of the two SLNs was similar, and both showed the biphasic drug release pattern
      with burst release at the initial stage and prolonged release afterwards. In
      contrast, the two SLNs demonstrated a marked difference in in vitro cellular
      cytotoxicity and in vivo tissue distribution performances. The IC(50) values of
      Cuc B in the two SLNs were by far lower than those of Cuc B solution and further
      Cuc B-GalSLN had about half the IC(50) value of Cuc B-CSLN. These results
      indicated that the encapsulation of Cuc B in SLNs resulted in the enhancement of
      cytotoxic activity, and galactosyl ligand could further enhance the cellular
      accumulation and cytotoxicity of Cuc B. The weighted-average overall drug
      targeting efficiency (Te) was used to evaluate the liver targetability. Cuc B
      GalSLN gave a relatively high (Te)(liver) value of 63.6%, approximately 2.5-times
      greater than that of Cuc B-CSLN (25.3%) and Cuc B solution (23.8%). In summary,
      the incorporation of N-HLBA into SLNs significantly enhanced the liver
      targetability of Cuc B-loaded SLNs and GalSLN had a great potential as a drug
      delivery carrier for improved liver targetability.

PMID- 20148710
TI  - Resolution of paroxysmal hemicrania after resection of intracranial meningioma.
AB  - Paroxysmal hemicrania is a trigeminal autonomic cephalalgia first described in
      1976, characterized by episodic attacks of excruciating unilateral periorbital
      and temporal stabbing, pulsatile, craw-like, or boring headaches lasting 2 - 30
      minutes, accompanied by autonomic features, and alleviated by indomethacin.
      Paroxysmal hemicrania is divided into an episodic or chronic form, depending on
      the duration and frequency of the attacks. We describe a case of paroxysmal
      hemicrania in a patient with a contralateral anterior clinoid meningioma, which
      resolved after tumor resection. Most cases of autonomic cephalgias are primary
      headaches and not caused by underlying intracranial structural lesions. Based on
      our patient and a literature review of secondary causes of trigeminal autonomic
      cephalalgias, we recommend that all patients with trigeminal autonomic
      cephalalgias including paroxysmal hemicrania undergo neuroimaging studies. The
      preferred neuro-radiologic procedure should be a cranial MRI to exclude
      underlying structural intracranial lesions, particularly in the sellar and
      parasellar regions.

PMID- 20148711
TI  - Investigation of self-microemulsifying and microemulsion systems for protection
      of prednisolone from gamma radiation.
AB  - Radiation is efficient for terminal sterilization. Unfortunately, its use for
      liquid pharmaceuticals is difficult. This work investigated the potential
      radioprotective effect of self-microemulsifying (SMEDDS), microemulsions and
      their phase transition systems which were reported to enhance ocular drug
      delivery. Prednisolone solutions were prepared in SMEDDS, W/O microemulsions
      containing, 5% w/w (ME 5%) or 10% w/w (ME 10%) water, liquid crystalline system
      with 25% water (LC) and coarse emulsion containing 80% water (EM). These were
      subjected to gamma irradiation with aqueous solution and suspension being used as
      control. The physical properties of the formulations were monitored and the
      chemical potency of the drug was determined using a stability indicating HPLC
      method. The phase behavior of the formulations was not affected by irradiation
      but the viscosity of LC was significantly reduced. The SMEDDS, ME 5% and ME 10%
      showed excellent radiation protection as indicated by no change in the chemical
      potency. The LC retained 84% and the EM retained 39.8% of the chemical potency
      after exposure to 20 KGy. The aqueous solution was extensively degraded with the
      suspension retaining only 73.5% of the potency at 20 KGy. SMEDDS and W/O
      microemulsion can thus protect prednisolone from degradation by ionizing
      radiation.

PMID- 20148712
TI  - Update on emerging drug therapies for systemic lupus erythematosus.
AB  - IMPORTANCE OF THE FIELD: Despite the improvement in survival of systemic lupus
      erythematosus (SLE), a cure for this chronic and disabling disease is still a
      myth. Refractory manifestations and treatment-related complications are still
      major causes for mortality and morbidity. More effective but less toxic therapies
      through modification of existing regimens, combination strategies or more
      specific targeting at the immunopathogenetic pathways are necessary. AREAS
      COVERED IN THIS REVIEW: The availability of biotechnology has led to the
      emergence of targeted therapies for SLE. In the past 5 years, there have been a
      number of clinical trials in the pipeline that involve existing drugs or novel
      biological agents. This article updates different novel therapeutic approaches in
      SLE that have emerged since 2006. WHAT THE READERS WILL GAIN: Readers will read
      the latest information and critical appraisals regarding recent clinical trials
      in lupus. Expert opinions on future directions of SLE treatment trials are also
      provided. TAKE HOME MESSAGE: SLE is a clinically and immunologically
      heterogeneous disease. Targeted therapies are currently available but to the
      disappointment of the lupus community, data from many recent clinical trials are
      unfavorable. While flaws and limitations in the study design and outcome measures
      may contribute to the futility of these trials, selection of SLE subsets by serum
      and cellular biomarkers may identify those who will benefit from these targeted
      therapies.

PMID- 20148713
TI  - In vitro and in vivo evaluation of oral tablet formulations prepared with
      ketoconazole and hydroxypropyl-beta-cyclodextrin.
AB  - The objective of this study was to enhance the solubility, dissolution rate, and
      oral bioavailability of a very poorly water-soluble anti-fungal agent,
      ketoconazole (KET), by inclusion complexation with a highly-soluble cyclodextrin
      derivative, hydroxypropyl-beta cyclodextrin (HP-beta-CD). Two groups of tablets
      containing KET alone and KET:HP-beta-CD (1:2) kneaded product (KP) including
      magnesium stearate and lactopress (anhydrous and spray-dried) as excipients were
      prepared by direct compression method. After the characterization studies, the in
      vitro dissolution studies of these tablets in simulated gastric fluid (SGF) and
      simulated intestinal fluid (SIF) were carried out. To evaluate the in vivo
      bioavailability, the tablets were administered orally to rabbits and drug levels
      in serum were determined by HPLC. Tablets containing the cyclodextrin complex
      showed a higher in vitro dissolution rate and bioavailability compared to the
      tablets containing KET alone.

PMID- 20148714
TI  - Autoimmune diseases: MIF as a therapeutic target.
AB  - IMPORTANCE OF THE FIELD: Autoimmune inflammatory diseases occur commonly in
      developed countries. The treatment of these diseases is usually non-curative and
      is aimed at suppressing inflammatory end-organ damage. Macrophage migration
      inhibitory factor (MIF) is a multipotent cytokine that has been implicated in the
      pathogenesis of numerous autoimmune inflammatory disorders. The selective
      targeting of MIF with either anti-MIF antibody or specific MIF antagonists may
      offer new therapeutic avenues for these diseases. AREAS COVERED IN THIS REVIEW:
      Our aim is to discuss MIF-directed therapies as a novel therapeutic approach. The
      review covers literature from the past 10 years. WHAT THE READER WILL GAIN: MIF
      inhibition has been shown to be efficacious in many experimental and pre-clinical
      studies of autoimmune inflammatory diseases. The close regulatory relationship
      between MIF and glucocorticoids makes therapeutic antagonism of MIF a potential
      steroid-sparing therapy in patients with refractory autoimmune diseases. TAKE
      HOME MESSAGE: We expect that MIF antagonism by either small-molecule- or antibody
      based approaches will find wide application in the treatment of autoimmune
      inflammatory diseases. Such therapy also may be informed by the MIF genotype of
      affected patients.

PMID- 20148715
TI  - NF-kappaB as a therapeutic target in chronic lymphocytic leukemia.
AB  - IMPORTANCE OF THE FIELD: NF-kappaB includes a family of transcription factors
      that play a critical role in the biology of normal lymphocytes and it is
      aberrantly activated in chronic lymphocytic leukemia (CLL) cells. Here, we review
      the role of constitutive NF-kappaB activation in CLL pathogenesis and its
      potential as a therapeutic target for CLL treatment. AREAS COVERED IN THIS
      REVIEW: This review highlights the different strategies reported to inhibit NF
      kappaB signaling in CLL cells. They include both IkappaB kinase inhibitors and
      several natural compounds that act at different steps of the pathway. WHAT THE
      READER WILL GAIN: Targeting NF-kappaB leads to apoptosis of CLL cells,
      corroborating the role of NF-kappaB in the survival and clonal expansion of these
      tumoral cells. Moreover, several studies confirmed a synergistic effect between
      NF-kappaB inhibitors and other antitumoral agents and that inhibition of NF
      kappaB could overcome the microenvironmental protection of CLL cells. TAKE HOME
      MESSAGE: NF-kappaB is a relevant target in CLL and inhibitors of this prosurvival
      pathway, alone or in combination, represent a novel therapeutic strategy for the
      treatment of CLL patients.

PMID- 20148716
TI  - Galanin receptor subtypes 1 and 2 as therapeutic targets in head and neck
      squamous cell carcinoma.
AB  - IMPORTANCE OF THE FIELD: Despite advances in the therapeutic approaches for head
      and neck squamous cell carcinoma (HNSCC) at some sites, no substantial
      improvement in treatment efficacy and survival has occurred over the past several
      decades. Recent application of molecular biology has focused on the importance of
      galanin and its receptors as potential therapeutic targets for HNSCC. AREAS
      COVERED IN THIS REVIEW: Our aim is to examine galanin receptor 1 (GALR1) and
      galanin receptor 2 (GALR2) as HNSCC therapeutic targets and explore opportunities
      and strategies for making use of GALR1 and GALR2 signaling. WHAT THE READER WILL
      GAIN: This review provides recent data about galanin receptor signaling and
      function in various cell types, especially HNSCC. Signaling through GALR1 induces
      cell cycle arrest and suppresses proliferation in HNSCC. Similar to GALR1, GALR2
      not only induces cell cycle arrest but also apoptosis, which was not observed
      with GALR1. TAKE HOME MESSAGES: GALR1 and GALR2 act as tumor suppressors in
      HNSCC, in a p53-independent manner. The current data suggest that GALR1 and GALR2
      are potentially significant therapeutic targets and prognostic factors in HNSCC.

PMID- 20148717
TI  - Therapeutic targeting of EGFR in malignant gliomas.
AB  - IMPORTANCE OF THE FIELD: Despite the improved prognosis for many cancer patients,
      the survival of those with malignant gliomas (MGs) remains dismal. Even with
      aggressive intervention, including surgery, chemotherapy and radiotherapy, the
      overall 2-year survival rate is only 25% in the most optimistic series, and 5
      year survival rates are consistently in the low single digits. Therefore, it is
      evident that novel therapeutic paradigms are necessary to overcome the inherent
      limitations of conventional treatments. EGFR gene overexpression can be found in
      40 - 50% of patients with MGs, whereas its expression is very low in normal
      brain. Therapeutic targeting of EGFR has indicated clinical success in the
      treatment of MGs. AREAS COVERED IN THIS REVIEW: The purpose of this review is to
      discuss the current status of several EGFR-targeted therapies in MGs patients and
      address the efficacy of these drugs as monotherapy or in combination with other
      drugs and/or treatments. We also emphasize the lessons learned and the future
      perspectives in the development of EGFR-targeted therapies for MGs. WHAT THE
      READER WILL GAIN: A more comprehensive understanding of the molecular, structural
      and biological characteristics of EGFR and the mechanisms of action of EGFR
      targeted antagonists will most likely contribute to the successful use of
      strategies of EGFR-targeted therapy in the clinic. TAKE HOME MESSAGE: Therapeutic
      targeting of EGFR include anti-EGFR mAbs, small-molecule EGFR tyrosine kinase
      inhibitors, peptide vaccination therapy and other therapeutic strategies. Each
      EGFR antagonist has its own advantages and limitations in terms of BBB crossing,
      ease of delivery, combination therapies and potential toxicity. Therefore, a
      multiple approach combining different agents that target EGFR signaling at
      multiple levels seems to have potential as future therapeutics for MGs, once the
      technical and safety issues unique to each of the approaches are overcome.

PMID- 20148718
TI  - Hsp90 as a therapeutic target in patients with oesophageal carcinoma.
AB  - IMPORTANCE OF THE FIELD: Oesophageal carcinoma has a poor prognosis with a 5-year
      overall survival rate of only 10 - 20%. The disease is often diagnosed at a late
      stage, when dissemination may already have occurred, contributing to the poor
      prognosis. However, recent developments in targeted therapy now offer new
      possibilities in the treatment arsenal. Heat shock protein 90 (Hsp90) has been
      demonstrated to protect oncogenic variants of signalling molecules from
      degradation, thus promoting cell growth and survival. Hsp90 has been found to be
      abundantly expressed in oesophageal cancer and may serve as a therapeutic target
      in the treatment of this disease. AREAS COVERED IN THIS REVIEW: We have
      summarised available data concerning the role of Hsp90 in oesophageal carcinoma
      as well as available information on other tumour types. WHAT THE READER WILL
      GAIN: To be able to elaborate on the molecular mechanisms of action of Hsp90 and
      discuss state-of-the-art of clinical trials involving Hsp90 inhibitors in
      malignancies, with a special emphasis on oesophageal cancer. TAKE HOME MESSAGE:
      Preclinical studies on Hsp90 inhibition in oesophageal cancer are promising and
      it is anticipated that in the near future clinical trials with Hsp90 inhibitors
      will be initiated also for oesophageal cancer, using the experience from other
      trials.

PMID- 20148719
TI  - Oxidative stress targets in pulmonary emphysema: focus on the Nrf2 pathway.
AB  - IMPORTANCE OF THE FIELD: Oxidative stress has been implicated in the pathogenesis
      of pulmonary emphysema. Nuclear factor erythroid-2-related factor 2 (Nrf2) a
      major antioxidant transcription factor could play a protective role in pulmonary
      emphysema. AREAS COVERED IN THIS REVIEW: Nrf2 is ubiquitously expressed
      throughout the lung, but is predominantly found in epithelium and alveolar
      macrophages. Evidence suggests that Nrf2 and several Nrf2 downstream genes have
      an essential protective role in the lung against oxidative stress from
      environmental pollutants and toxicants such as cigarette smoke, a major causative
      factor for the development and progression of pulmonary emphysema. Application of
      Nrf2-deficient mice identified an extensive range of protective roles for Nrf2
      against the pathogenesis of pulmonary emphysema. Therefore, Nrf2 promises to be
      an attractive therapeutic target for intervention and prevention strategies. WHAT
      THE READER WILL GAIN: In this review, we discuss recent findings on the
      association of oxidative stress with pulmonary emphysema. We also address the
      mechanisms of Nrf2 lung protection against oxidative stress based on emerging
      evidence from experimental oxidative disease models and human studie. TAKE HOME
      MESSAGE: The current literature suggests that among oxidative stress targets,
      Nrf2 is a valuable therapeutic target in pulmonary emphysema.

PMID- 20148720
TI  - Association of hyperhomocysteinemia with left ventricular dilatation and mass in
      human heart.
AB  - BACKGROUND: Hyperhomocysteinemia is a risk factor for ischemic heart disease.
      Several other mechanisms apply also to dilative types of heart failure of
      various, non-ischemic etiologies. We hypothesized that hyperhomocysteinemia is
      associated with left ventricular (LV) dilatation and hypertrophy in dilative
      cardiomyopathy. METHODS: Homocysteine was measured in 66 individuals with
      suspected cardiomyopathy. Cardiac magnetic resonance imaging was used to assess
      LV volume, mass, and wall stress. RESULTS: Hyperhomocysteinemia (> 12 micromol/L)
      was found in 45 patients (68%). LV mass was greater in these patients compared
      with individuals with normal homocysteine (83+/-27 vs. 67+/-19 g/m(2); p<0.02).
      Homocysteine was increased in patients with increased brain natriuretic peptide >
      or = 100 pg/mL (18.3+/-5.9 vs. 14.9+/-5.1 micromol/L; p=0.018). LV mass, LV end
      diastolic and end-systolic volume (LVEDV, LVESV) were significantly increased in
      individuals in the upper quartile compared with the lower quartile (90+/-25 vs.
      65+/-18 g/m(2), p=0.021; 114+/-50 vs. 71+/-23 mL/m(2), p=0.042; 76+/-51 vs. 36+/
      22 mL/m(2), p=0.045). LV dilatation (LVEDV > or = 90 mL/m(2)) was more common in
      hyperhomocysteinemia (> 12 micromol/L, p=0.0166). Normalized LV mass was
      correlated with homocysteine (r=0.346, p=0.065). Homocysteine was not
      significantly correlated with LVEDV (r=0.229, p=0.065), LV end-diastolic wall
      stress (r=0.226, p=0.069) and LV ejection fraction. CONCLUSIONS:
      Hyperhomocysteinemia appears to be, at least in part, involved in a
      disproportional LV dilatation, where the ensuing hypertrophy is not sufficient to
      compensate for the increased wall stress. A potential mechanism is the
      hyperhomocysteinemia associated increase in oxidative stress that favors muscle
      fiber slippage.

PMID- 20148721
TI  - High specificity but low sensitivity of the cartilage oligomeric matrix protein
      (COMP) test in rheumatoid arthritis and osteoarthritis.

PMID- 20148722
TI  - Contemporary platelet function testing.
AB  - Defects in primary hemostasis typically lead to a bleeding diathesis and include
      several disorders, such as von Willebrand disease and various platelet function
      defects that may arise because of failure of membrane receptors, deficiencies in
      internal storage organelles, and/or signal transduction problems. The laboratory
      identification of a primary hemostasis defect including platelet function defects
      now involves a multi-step process. These processes begin with a full blood count
      to assess platelet count and size, progressing, if necessary, to platelet
      aggregation studies, and leading to further specific testing including flow
      cytometry, electron micro-scopy and/or genetic testing. This review outlines the
      sequential process of platelet function investigations, and discusses each of the
      essential components in some detail.

PMID- 20148723
TI  - Disparity in estimated average glucose due to different hemoglobin A1c methods
      and hemoglobin S trait.

PMID- 20148724
TI  - Pregnancy-associated plasma protein-A as a marker for long-term mortality in
      patients with peripheral atherosclerosis: inconclusive findings from the Linz
      Peripheral Arterial Disease (LIPAD) study.
AB  - BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) has been associated
      with peripheral artery disease (PAD). The aim of this study was to evaluate the
      utility of PAPP-A as a marker for long-term mortality in patients with
      atherosclerotic PAD. METHODS: PAPP-A serum concentrations were measured using an
      enzymatically amplified two-step sandwich-type immunoassay in 487 consecutive
      patients admitted to a tertiary care hospital with symptomatic PAD. The main
      outcome measure was all-cause mortality at 5 years. RESULTS: During follow-up,
      114 patients died and 373 survived. The median PAPP-A concentration was higher
      among decedents compared with survivors (0.96 vs. 0.78 mU/L, p=0.024). The area
      under the receiver operating characteristic curve for the prediction of 5-year
      mortality by PAPP-A was 0.57 [95% confidence interval (CI), 0.53-0.61; p=0.026].
      Survival probability was not significantly associated with PAPP-A concentrations
      using Kaplan-Meier curve analysis. However, univariate Cox proportional-hazards
      regression analysis revealed that PAPP-A was associated with 5-year mortality
      [risk ratio 1.25; 95% CI, 1.05-1.50; p=0.013 per one standard deviation (SD)
      increase in log transformed values]. In the multivariate model using a
      bootstrapping method, the predictive value of PAPP-A remained significant (risk
      ratio 1.31; 95% CI, 1.01-1.73; p=0.024 per 1 SD increase in log transformed
      values), even after adjustment for clinical confounders and other biomarkers,
      such as high-sensitivity C-reactive protein and amino terminal pro-B-type
      natriuretic peptide. CONCLUSIONS: In this study, PAPP-A was an independent
      predictor of 5-year all-cause mortality in patients with symptomatic PAD.
      However, based on the weak association between PAPP-A and outcome in our cohort,
      we consider PAPP-A measurements to not be useful in clinical practice for
      prognostic purposes in patients with PAD.

PMID- 20148725
TI  - Correlation between glucose and bupivacaine levels in cerebrospinal fluid after
      spinal anesthesia: glycorrhachia as predictor for duration of sensory block.
AB  - BACKGROUND: Prediction of the duration of motor block after injection of a local
      anesthetic into cerebrospinal fluid (CSF) would be a very useful tool in clinical
      practice. However, previous attempts have not shown conclusive results. In this
      work, glycorrhachia is demonstrated to be an adequate predictive parameter after
      spinal anesthesia using 0.5% hyperbaric bupivacaine. METHODS: Two mL of local
      anesthetic through a continuous spinal catheter was administered to 40 patients.
      CSF was sampled at different time intervals from the onset of infusion to motor
      recovery. CSF bupivacaine concentrations were measured using chromatography. An
      automated analyzer was used for determining glycorrhachia in the same samples.
      RESULTS: For all patients, good correlation (r(2)>0.95, p<0.05) was obtained.
      From these results, it was possible to develop a general model which establishes
      the relationship between CSF glucose and bupivacaine concentrations (R(2)=0.987,
      p<0.05). Motor block is reached when CSF glucose concentration is about 245 mg/dL
      (13.5 mmol/L), which corresponds to 35 microg/mL of bupivacaine. CONCLUSIONS:
      Glycorrhachia measured during surgical intervention in patients undergoing spinal
      anesthesia with hyperbaric bupivacaine provides a mechanism for predicting the
      duration of motor block in a rapid and simple manner.

PMID- 20148726
TI  - Comparison of different depletion strategies for improving resolution of the
      human urine proteome.
AB  - BACKGROUND: Urine, being an ultrafiltrate of plasma, is a rich source for
      biomarker discovery. Since potential new disease markers are often present in low
      concentrations, a prefractionation/enrichment step could be useful in the
      discovery process. To enhance the detection of low-abundance proteins, three
      immuno-affinity depletion approaches were evaluated. METHODS: To remove the most
      abundant proteins from a human urine sample, GenWay Spin IgY-12 kit, HPLC Agilent
      Hu-PL7 and a home-made column vs. human serum albumin [immuno-affinity column
      (IAC)] were compared. Quantification of total proteins, 2-D gel electrophoresis
      (2-DE), Progenesis gel images analysis and mass spectrometric proteins
      identification were applied to evaluate these strategies. RESULTS:
      Reproducibility of depletion columns, by estimating protein content of unbound
      fractions, were: 343+/-20.0 microg, 5.8%; 186.3+/-13.3 microg, 7.2%; 292+/-20.6
      microg, 8.8% [mean+/- standard deviation (SD), CV%], for GenWay, Agilent and IAC
      methods, respectively. To isolate urinary protein after depletion, ethanol
      precipitation provided the highest recovery (80%). Applying 2-DE and Progenesis
      analysis, the number of spots visualized on the gels was 468+/-21, 331+/-7, 368+/
      22 and 304+/-7 (mean+/-SD) for GenWay, Agilent, IAC, and the undepleted urine
      pool sample, respectively, with a significant difference p<0.001 compared to the
      GenWay procedure. CONCLUSIONS: The sequential procedure of urine samples using
      multi-protein immuno-affinity depletion represents a valid tool for simplifying 2
      DE analysis of the urine proteome. Particularly, the GenWay kit followed by
      ethanol precipitation was found to be the most efficient method for exploring the
      urine proteome.

PMID- 20148727
TI  - Beware of carryover in modern chemistry analyzers.
AB  - BACKGROUND: Random-access analyzers that employ dedicated probes may be affected
      by carryover. Sample carryover, involving analyte from one sample that is
      measured in a subsequent sample, is most often detected in measurement procedures
      that have wide reportable ranges. However, reagent carryover can be more
      difficult to detect as it may involve only one pair of measurement procedures.
      METHODS: Our laboratory noted several patient samples with total cholesterol
      <2.58 mmol/L (100 mg/dL) during the initial months after a new chemistry analyzer
      was installed. The problem seemed to occur intermittently, approximately once per
      week. RESULTS: Immediate reanalysis of affected samples resulted in measured
      values that were 1.03-2.58 mmol/L (40-100 mg/dL) higher. Evaluation of reagent
      carryover revealed a significant decrease in total cholesterol after analysis of
      creatine kinase (EC 2.7.3.2). Carryover disappeared when an additional reagent
      probe wash was applied, whereas the root of the problem was eliminated with
      replacement of the reagent probes. The insidious nature of reagent carryover made
      it difficult to initially detect the problem, which affected two of the three
      instruments in our laboratory. CONCLUSIONS: Laboratorians should be aware of the
      potential for carryover in random access analyzers, and should be mindful of
      appropriate troubleshooting techniques.

PMID- 20148729
TI  - Menopausal symptoms and the metabolic syndrome in Nigerian women with type 2
      diabetes mellitus.
AB  - OBJECTIVE: To determine the frequency of occurrence of the metabolic syndrome and
      the age of onset and pattern of menopausal symptomatology in Nigerian women with
      type 2 diabetes mellitus. METHODS: This was a cross-sectional study in which 201
      menopausal women with type 2 diabetes mellitus aged between 40 and 85 years were
      studied. Their anthropometric indices, fasting lipid values, glucose parameters,
      uric acid and HbA(1c) were documented. The presence of the metabolic syndrome and
      menopausal symptoms were determined using the National Cholesterol Panel-ATP
      definition and MENQOL questionnaire, respectively. The test statistics used
      included the t test, chi(2) and correlation coefficient. RESULTS: The mean age
      (standard deviation) of the onset, median age and age range of menopause were
      50.3 (4.8) years, 50 years and 40-57 years, respectively. The frequency of
      occurrence of menopausal symptoms ranged from 14% to 76%. Hot flushes, night
      sweats and dry skin are some of the vasomotor symptoms which occurred in 38%, 31%
      and 30%, respectively, of the subjects. The prevalence of the metabolic syndrome
      was 69%, with the pattern of occurrence of the menopausal symptoms being
      comparable in subjects with and without the metabolic syndrome. The frequency of
      occurrence of hyperuricemia in the study population was 42%. In the partial
      correlation analysis, serum uric acid concentration was significantly positively
      correlated with body mass index (r = 0.15, p = 0.02) and significantly negatively
      correlated with high density lipoprotein cholesterol (r = -0.1, p = 0.03).
      CONCLUSION: The age of onset of menopause in Nigerian women with type 2 diabetes
      mellitus is comparable to the age that is commonly reported and the metabolic
      syndrome is highly prevalent in this group of women.

PMID- 20148728
TI  - Procalcitonin measurement in routine emergency medicine practice: comparison
      between two immunoassays.
AB  - BACKGROUND: Accurate identification of bacterial infections in patients
      presenting at the emergency department is crucial for early and rational
      antibiotic treatment. In this situation, using a cut-off of 0.25 microg/L for
      procalcitonin allows for carefully monitoring of febrile patients. Most previous
      studies have been performed with the reference B.R.A.H.M.S PCT KRYPTOR assay. The
      goal of this study was to compare this test with the VIDAS B.R.A.H.M.S PCT((R))
      assay and to validate clinically relevant cut-off thresholds. METHODS: This
      prospective study was conducted in adults presenting to the emergency departments
      of a tertiary hospital. We included 305 consecutive patients that had
      procalcitonin requested. Procalcitonin was measured first with the KRYPTOR, then
      with the VIDAS systems. Statistical analysis consisted in Passing and Bablok and
      Bland-Altman plots. RESULTS: In the overall cohort, 176 patients had
      procalcitonin concentrations measured using both methods and were well
      correlated. The Bland-Altman plot exhibited a bias of 0.108 [95% confidence
      interval: -0.044 to 0.260]. The concordance at different procalcitonin cut-off
      thresholds, respectively of 0.1, 0.25, 0.5 and 2 microg/L, indicated that above
      0.25 microg/L, the kappa coefficient was >0.80. CONCLUSIONS: A highly significant
      correlation was observed between the two automated assays. Procalcitonin
      concentrations obtained from both methods led to the same clinical
      interpretation.

PMID- 20148730
TI  - Indications and limitations of perineal ultrasound examination.

PMID- 20148732
TI  - Use of Gascon and Pronase either as a pre-endoscopic drink or as targeted
      endoscopic flushes to improve visibility during gastroscopy: a prospective,
      randomized, controlled, blinded trial.
AB  - OBJECTIVE: To assess whether endoscopic flushes of the bubble-bursting agent
      Gascon and the mucolytic agent Pronase are as effective in terms of improving
      endoscopic mucosal visibility as a pre-endoscopic drink of the same agents.
      MATERIAL AND METHODS: A total of 112 patients attending a Japanese tertiary
      referral centre for upper gastrointestinal endoscopy were randomized to receive
      either the standard Japanese procedure of a pre-endoscopic drink of water
      containing Gascon and Pronase with endoscopic flushes of 20-ml aliquots of water,
      or no pre-endoscopic therapy but endoscopic flushes of 20-ml aliquots of water
      containing Gascon, with or without Pronase as necessary. RESULTS: Visibility
      scores were significantly better in the pre-endoscopic drink group than in either
      of the endoscopic flush groups. The group receiving a pre-endoscopic drink
      required fewer flushes during the procedure and there was no difference in the
      endoscopic time between the three groups. CONCLUSIONS: Our results suggest that
      endoscopic spraying of these bubble-bursting and mucolytic agents is not able to
      offer equivalent improvements in endoscopic mucosal visibility when compared with
      the standard Japanese therapy of a pre-endoscopic drink of these agents. The
      addition of Pronase to the spray solution had no measurable benefit over Gascon
      alone. We therefore cannot recommend endoscopic spraying of mucous clearing
      agents over their use as a pre-endoscopic drink.

PMID- 20148733
TI  - Inter-observer agreement on the interpretation of capsule endoscopy findings
      based on capsule endoscopy structured terminology: a multicenter study by the
      Korean Gut Image Study Group.
AB  - OBJECTIVE: Capsule endoscopy (CE) is a novel investigation for the diagnosis of
      small-bowel disease but its interpretation is highly subjective. We studied the
      inter-observer agreement and accuracy of the interpretation of CE findings based
      on capsule endoscopy structured terminology (CEST). MATERIAL AND METHODS: Fifty
      six CE video clips were collected from eight university hospitals in South Korea
      and were independently reviewed by 13 gastroenterology experts and 10 trainees.
      All investigators recorded their findings based on CEST. To determine the
      accuracy of individual viewers, we defined the 'gold standard' as a joint review
      by four experts. RESULTS: The 56 CE video clips included five normal cases, 19
      cases of protruding lesions, 21 cases of depressed lesions, three cases of flat
      lesions, one case of abnormal mucosa, six cases with blood in the lumen, and one
      case of stenotic lumen. The overall mean accuracies for the experts and trainees
      were 74.3% +/- 22.6% and 61.7% +/- 25.4%, respectively. The overall accuracy for
      the trainee group was significantly lower than that for the expert group (P <
      0.001), especially in normal, tumor, venous structure, and ulcer cases. The
      accuracies of the two groups varied with the CE findings. The accuracies were
      higher in cases with more prominent intraluminal changes (e.g. active small-bowel
      bleeding, ulcer, tumor, stenotic lumen). In contrast, subtle mucosal lesions,
      such as erosion, angioectasia, and diverticulum, had lower accuracies. The mean
      kappa values for the experts and trainees were 0.61 (range 0.39-0.97) and 0.46
      (range 0.17-0.66), respectively. CONCLUSIONS: Our results showed that there was
      substantial agreement between experts and moderate agreement between trainees. In
      order to achieve higher accuracies and better inter-observer agreement, we need
      not only more experience with CE but also consensus regarding CEST terminology.

PMID- 20148735
TI  - VerifyNow and VASP phosphorylation assays give similar results for patients
      receiving clopidogrel, but they do not always correlate with platelet
      aggregation.
AB  - Point-of-care testing permits an evaluation of the efficacy of drugs used in the
      treatment of acute coronary syndromes (ACS). An increased risk of thrombosis
      after coronary stenting for ACS patients treated with aspirin and clopidogrel has
      been linked to high platelet reactivity and, for certain patients, poor drug
      response. The objective of our study was to compare the VerifyNow-P2Y12 device
      with the VASP (vasodilator-stimulated phosphoprotein) phosphorylation assay and
      ADP-induced platelet aggregation as assessed by light transmission aggregometry
      in a group of 81 ACS patients (100 tests) treated in our hospital. There was a
      good correlation between VerifyNow-P2Y12 and VASP especially during the chronic
      phase of one month or more after the ischemic event, whereas discordance was
      sometimes seen with platelet aggregometry. The rapidity and ease of use of the
      VerifyNow device suggests that it has a valuable place in point-of-care testing
      of ACS patients.

PMID- 20148736
TI  - Effects of intracameral use of adrenalin solution with preservative on corneal
      endothelium.
AB  - OBJECTIVE: To evaluate the effects of injection of 1:100,000 dilution adrenalin
      with sodium bisulfite preservative on the corneal endothelium in
      phacoemulsification cataract surgery. METHODS: This retrospective study comprised
      70 patients with age-related cataracts who had undergone phacoemulsification
      cataract surgery with intraocular lens (IOL) implantation without any surgical
      complications. In the adrenalin group, patients with intraoperative intracameral
      adrenalin use were included. The intracameral adrenalin was composed of 1 mL of
      1:100,000 dilution adrenalin with sodium bisulfite preservative. The control
      group included patients who underwent surgery without any intracameral adrenaline
      use. There were 36 patients in the adrenalin group and 34 patients in the control
      group. Corneal endothelial density, endothelial cell morphology, and endothelial
      cell area were measured via specular microscopy both preoperatively and 3 months
      after surgery. The 2 groups were compared with regard to changes in specular
      microscopy measurements. RESULTS: The mean (+/- standard deviation) age was 66.51
      +/- 8.32 years in the adrenalin group and 67.58 +/- 7.83 years in the control
      group. The difference in age between the 2 groups was not significant (p = .611).
      The preoperative mean corneal endothelial cell density was 2,270 +/- 286
      cells/mm(2) in the adrenalin group and 2,226 +/- 260 cells/mm(2) in the control
      group, and the difference between the 2 groups was not statistically significant
      (p = .550). In the adrenalin group, the postoperative mean corneal endothelial
      cell density was 2,191 +/- 268 cells/mm(2). Although the postoperative mean cell
      density was lower than the preoperative mean cell density, the difference between
      the 2 measurements was not statistically significant (p = .117). In the control
      group, the postoperative mean corneal endothelial cell density was 2,169 +/- 272
      cells/mm(2), and the difference between the preoperative and postoperative
      measurements was not statistically significant (p = .161). Comparisons of
      postoperative specular microscopy measurements between the adrenalin and control
      groups with regard to cell density, cell sizes, and cell shapes showed that there
      were no statistically significant differences in comparison of all parameters
      between the 2 groups. CONCLUSIONS: Intracameral injection of 1:100,000 dilution
      adrenalin with sodium bisulfite preservative is not toxic to corneal endothelium.

PMID- 20148737
TI  - An unusual case of "jaundice".

PMID- 20148738
TI  - Serum resistin and adiponectin levels in young non-obese women with polycystic
      ovary syndrome.
AB  - INTRODUCTION: Although polycystic ovary syndrome (PCOS) was described more than
      half a century ago, the underlying cause of PCOS is still unknown. The aim of our
      study was to evaluate whether serum resistin and adipocytokine levels alter and
      its changes relate with low grade inflammation in non-obese young women with
      PCOS. SUBJECTS AND METHODS: Newly diagnosed 31 young non-obese women with PCOS
      (mean age 21.8 +/- 5.4 years; body mass index (BMI): 23.8 +/- 6.6 kg/m(2)) and 25
      BMI- and age-matched, regular-cycling, healthy women (mean age 24.9 +/- 5.7
      years; BMI: 23.1 +/- 5.8 kg/m(2)) were included the study Anthropometric
      measurements were evaluated. Resistin, adiponectin, glucose, insulin, hormone
      profiles, Lipoprotein (Lp)(a), high sensitive C reactive protein (hs-CRP), and
      homocysteine levels were measured in the beginning of oral glucose tolerance
      test. Homeostasis model assessment of insulin resistance (HOMA-IR) was
      calculated. RESULTS: Non-obese young women with PCOS had high adiponectin levels
      (28.01 +/- 6.47 ng/ml in PCOS vs. 23.89 +/- 7.70 ng/ml in control subjects, p =
      0.034), whereas serum resistin levels were not significantly different compared
      with healthy controls (14.14 +/- 6.6 ng/ml in PCOS vs. 13.78 +/- 4.26 ng/ml in
      control subjects). There were no significant differences between two groups in
      terms of fasting insulin, Lp(a), homocysteine, and hs-CRP levels. Mean HOMA-IR
      value of patients with PCOS was similar with control subjects (1.93 +/- 0.73 in
      PCOS; 1.15 +/- 0.54 in control group). CONCLUSIONS: Resistin levels did not
      change in non-obese young women with PCOS whereas adiponectin level in non-obese
      young women with PCOS was significantly higher than control subjects, perhaps,
      because of no insulin resistance. Circulating resistin levels may not be
      candidate to play a role in pathogenesis of PCOS without insulin resistance or
      obesity.

PMID- 20148739
TI  - Clinical, metabolic, and endocrine parameters in response to metformin and
      lifestyle intervention in women with polycystic ovary syndrome: a randomized,
      double-blind, and placebo control trial.
AB  - The aim of this study was to evaluate the effects of metformin in addition to
      diet and exercise on endocrine and metabolic disturbances in women with
      polycystic ovary syndrome (PCOS) in a prospective, double-blind, randomized,
      placebo (PBO) control trial. Thirty women with insulin resistance and PCOS
      received lifestyle modification and 1500 mg of metformin or placebo for 4 months.
      Before and after treatment, body mass index, waist/hip ratio, blood pressure,
      hirsutism, and menstrual patterns were evaluated. Serum concentrations of
      gonadotropins, androgens, progesterone, glucose, insulin, and lipids were
      measured. Lifestyle interventions resulted in similar weight and menstrual
      cycle's improvements in both groups. A significant reduction in serum fasting
      insulin, HOMA index, waist and testosterone levels was only observed with
      metformin. There were no significant changes in androstenedione,
      dehydroepiandrosterone sulfate, gonadotropins, and lipids levels. No other
      changes were observed in hirsutism or blood pressure. These findings suggest that
      metformin has an additive effect to diet and exercise to improve parameters of
      hyperandrogenism and insulin resistance. Although, a small decrease in body
      weight trough lifestyle changes could be enough to improve menstrual cycles in
      insulin-resistant women with PCOS.

PMID- 20148741
TI  - Update on gestational diabetes.

PMID- 20148740
TI  - Effect of coasting on IVF cycle characteristics and outcome in short vs. long
      GnRH agonist protocols.
AB  - AIMS: To compare the results of IVF cycles following coasting in patients treated
      with long versus short GnRH agonist protocols. METHODS: A retrospective
      comparative study in which all women aged 35 years or less attending the IVF unit
      from 2000 to 2006 in whom coasting was used in GnRH agonist protocols were
      included. Data on coasting-related variables and outcome were collected from the
      files and compared between the short GnRH agonist (n = 78) and long GnRH agonist
      (n = 181) cycles. RESULTS: The short GnRH agonist cycles were characterized by
      higher E2 levels during coasting and longer duration of coasting than the long
      GnRH agonist cycles. Although the number of retrieved oocytes was lower following
      coasting in the short protocol, there was no difference between the groups in
      fertilization rate, number of high-quality embryos available for transfer, and
      pregnancy rate. Pregnancy rate in both protocols was negatively correlated to E2
      level at initiation of coasting. The overall moderate and severe OHSS rate after
      coasting was 5.1% in the short-protocol group and 6.0% in the long-protocol group
      (p = 0.76). CONCLUSIONS: The ovarian response curve to coasting is longer in the
      short than in the long GnRH-agonist protocol, but there is no significant
      difference in pregnancy or OHSS rates.

PMID- 20148742
TI  - The glyburide report card.
AB  - Over the past decade, several studies have been published describing the use of
      glyburide for the treatment of women with gestational diabetes (GDM). These
      studies include randomized prospective trials, prospective studies, and cohort
      studies. With a total of more than 1000 patients, they encompass a wide range of
      patient populations and treatment centers and demonstrate the effectiveness of
      oral treatment in achieving good glycemic control in women with GDM. Taken
      together, these studies have demonstrated that glyburide is as safe and as useful
      as insulin for the treament of women with GDM and will likely become universally
      accepted as the first line drug of choice for treatment of this condition.

PMID- 20148743
TI  - Changing the diagnosis criteria of type 2 diabetes in pregnancy: do the ends
      justify the means?
AB  - Diabetes in pregnancy is a chronic disease that demands pharmacological therapy,
      time consuming, with frequent fetal testing and adherence to diet protocol. Given
      the consensus that glucose control is the key to maximizing outcome, how can the
      complication rate in the GDM and type 2 diabetes reveal a 3-5 fold rate of
      perinatal complication compared to the normal population? This review will
      address the scope of the problem reinforcing the need to address several issues.
      Should the diagnostic criteria for type 2 diabetes be altered or redefined, at
      least in pregnancy due to similarities that exist between GDM impaired glucose
      tolerance and type 2 diabetes.

PMID- 20148744
TI  - Emerging cardiometabolic complications of androgen deprivation therapy.
AB  - Prostate cancer (PCa) is the most common malignancy in men. Androgen deprivation
      therapy (ADT) is used in the treatment of locally advanced and metastatic PCa.
      Although its use has improved survival in a subset of patients, it also has
      negative consequences. Osteoporosis, sexual dysfunction, hot flashes and adverse
      changes in body composition are well-known and well-studied complications of ADT.
      Recent studies have also found metabolic complications in these men such as
      insulin resistance, diabetes and metabolic syndrome. In addition, these men might
      also experience higher cardiovascular mortality. Studies are needed to determine
      the mechanism behind these complications and to employ strategies to prevent
      them.

PMID- 20148745
TI  - Diversity of bone cell activity as a histomorphometric feature of idiopathic
      osteoporosis in men.
AB  - Although osteoporosis in men is an increasing health problem, studies on
      osteoporosis in males are still scarce. The aim of our study was to determine the
      characteristics of bone tissue and bone turnover in men with idiopathic
      osteoporosis. Transiliac crest bone samples were histomorphometrically analyzed
      after double tetracycline labeling in 32 men aged 37-65 years who were diagnosed
      with idiopathic osteoporosis by densitometry of the lumbar spine and hip. Bone
      volume, osteoid surface, osteoblast surface, eroded surface, osteoid thickness,
      trabecular thickness, trabecular number, trabecular separation, and mineral
      apposition rate (MAR) were determined in all trabecular bone specimens. Bone
      volume and structural parameters indicated trabecular bone loss in most patients.
      Cellular parameters and MAR indicated variations in bone cell actions. No age
      related decrease in histomorphometric parameters was found. After the patients
      were grouped according to MAR values, osteoblast and eroded surfaces were found
      to be lower in the group with decreased MAR values and elevated in the group of
      patients with increased MAR parameter. Trabecular thickness was greater in
      patients with lower than normal MAR, due to reduced resorption and probably loss
      of very thin trabeculae. Our results suggest that idiopathic osteoporosis in man
      resembles many characteristics of postmenopausal osteoporosis in women resulting
      in impaired trabecular structure due to unbalanced cellular activity and bone
      turnover rate.

PMID- 20148746
TI  - The effectiveness of intermittent rat parathyroid hormone (1-34) treatment on low
      bone mass due to oestrogen or androgen depletion in skeletally mature rats.
AB  - Rat parathyroid hormone (PTH) 1-34 (4 microg/kg/day) was applied for 2.5 months
      to 9 month-old rats immediately after ovariectomy or orchidectomy or to 15 month
      old rats with low bone mass which had been castrated 6 months before in order to
      know the effects on serum biochemistry parameters, lumbar and femoral bone
      mineral density, histology, cancellous and cortical bone histomorphometry,
      mineralisation content profile in cortical bone by backscattered-electron
      microscopy, and femoral torsion biomechanical testing. In ovariectomised rats,
      preventive PTH treatment avoided cancellous bone loss in tibial metaphysis and
      partially in lumbar vertebra, while in cortical bone, PTH increased endosteal
      resorption and periosteal formation. In intervention study, PTH did not restore
      cancellous bone but a strong endosteal and periosteal new bone formation was
      detected. In orchidectomised rats, PTH, in preventive study, avoided cancellous
      bone loss in metaphysis and lumbar vertebra, and a mild new bone formation in
      cortical bone was found. In intervention study, PTH maintained baseline
      cancellous bone mass, but in cortical bone a strong endosteal and periosteal new
      bone formation was detected. The PTH-induced new bone formation was confirmed by
      histology and by mineral content profiles. After castration, biomechanical
      properties were affected in females but not in male rats and PTH reverted this
      effect.

PMID- 20148747
TI  - Effect of smoking parameters on the particle size distribution and predicted
      airway deposition of mainstream cigarette smoke.
AB  - It is known that puffing conditions such as puff volume, duration, and frequency
      vary substantially among individual smokers. This study investigates how these
      parameters affect the particle size distribution and concentration of fresh
      mainstream cigarette smoke (MCS) and how these changes affect the predicted
      deposition of MCS particles in a model human respiratory tract. Measurements of
      the particle size distribution made with an electrical low pressure impactor for
      a variety of puffing conditions are presented. The average flow rate of the puff
      is found to be the major factor effecting the measured particle size distribution
      of the MCS. The results of these measurements were then used as input to a
      deterministic dosimetry model (MPPD) to estimate the changes in the respiratory
      tract deposition fraction of smoke particles. The MPPD dosimetry model was
      modified by incorporating mechanisms involved in respiratory tract deposition of
      MCS: hygroscopic growth, coagulation, evaporation of semivolatiles, and mixing of
      the smoke with inhaled dilution air. The addition of these mechanisms to MPPD
      resulted in reasonable agreement between predicted airway deposition and human
      smoke retention measurements. The modified MPPD model predicts a modest 10% drop
      in the total deposition efficiency in a model human respiratory tract as the puff
      flow rate is increased from 1050 to 3100 ml/min, for a 2-s puff.

PMID- 20148748
TI  - Cardiopulmonary response to inhalation of biogenic secondary organic aerosol.
AB  - An irradiation chamber designed for reproducible generation of inhalation test
      atmospheres of secondary organic aerosol (SOA) was used to evaluate
      cardiopulmonary responses in rodents exposed to SOA derived from the oxidation of
      alpha-pinene. SOA atmospheres were produced with 10:1 ratios of alpha
      pinene:nitrogen oxides (NO(x)) and 10:1:1 ratios of alpha-pinene:nitrogen
      oxides:sulfur dioxide (SO(2)). SOA atmospheres were produced to yield 200 microg
      m(-3) of particulate matter (PM). Exposures were conducted downstream of
      honeycomb denuders employed to remove the gas-phase precursors and reaction
      products. Nose-only exposures were conducted with both rats (pulmonary effects)
      and mice (pulmonary and cardiovascular effects). Composition of the atmospheres
      was optimized to ensure that the SOA generated resembled SOA observed in previous
      irradiation studies, and contained specific SOA compounds of interest (e.g.,
      organosulfates) identified in ambient air. Pulmonary and cardiovascular toxicity
      were measured in two different rodent species. In situ chemiluminescence and
      thiobarbituric acid- reactive substances (TBARS) were used to evaluate oxidative
      reactions in the F344 rats. ApoE(-/-) mice were exposed for 7 days and
      measurements of TBARS and gene expression of heme oxygenase-1 (HO-1), endothelin
      1 (ET-1), matrix metalloproteinase-9 (MMP-9) were made in aorta. Pulmonary
      inflammatory responses in both species were measured by bronchoalveolar lavage
      fluid (BALF) cell counts. No pulmonary inflammation was observed in either
      species. A mild response was observed in mouse aorta for the upregulation of HO-1
      and MMP-9, but was not seen for ET-1. Overall, alpha-pinene-derived SOA,
      including SOA that included organosulfate compounds, revealed limited biological
      response after short-term inhalation exposures.

PMID- 20148749
TI  - Quantitative evaluation of infection control models in the prevention of
      nosocomial transmission of SARS virus to healthcare workers: implication to
      nosocomial viral infection control for healthcare workers.
AB  - Healthcare workers (HCWs) are at high risk of acquiring emerging infections while
      caring for patients, as has been shown in the recent SARS and swine flu
      epidemics. Using SARS as an example, we determined the effectiveness of infection
      control measures (ICMs) by logistic regression and structural equation modelling
      (SEM), a quantitative methodology that can test a hypothetical model and
      validates causal relationships among ICMs. Logistic regression showed that
      installing hand wash stations in the emergency room (p = 0.012, odds ratio =
      1.07) was the only ICM significantly associated with the protection of HCWs from
      acquiring the SARS virus. The structural equation modelling results showed that
      the most important contributing factor (highest proportion of effectiveness) was
      installation of a fever screening station outside the emergency department (51%).
      Other measures included traffic control in the emergency department (19%),
      availability of an outbreak standard operation protocol (12%), mandatory
      temperature screening (9%), establishing a hand washing setup at each hospital
      checkpoint (3%), adding simplified isolation rooms (3%), and a standardized
      patient transfer protocol (3%). Installation of fever screening stations outside
      of the hospital and implementing traffic control in the emergency department
      contributed to 70% of the effectiveness in the prevention of SARS transmission.
      Our approach can be applied to the evaluation of control measures for other
      epidemic infectious diseases, including swine flu and avian flu.

PMID- 20148750
TI  - (Post-traumatic) embitterment disorder: critical evaluation of its stressor
      criterion and a proposed revised classification.
AB  - BACKGROUND: In 2003, the German psychiatrist Michael Linden proposed the new
      mental disorder concept of "post-traumatic embitterment disorder (PTED)". PTED is
      defined as the mental reaction to a critical event that is normal, but not
      everyday, such as conflict at work. The patient sees this event as unjust and as
      a violation of basic beliefs. The principal aspect of the reaction pattern is a
      prolonged feeling of embitterment. AIM: In the present paper, the concept of PTED
      is systematically evaluated. Moreover, future developments in terms of diagnostic
      systems of mental disorders (ICD-11, DSM-V) are addressed. RESULTS: The
      evaluation of critical points concerning PTED revealed that the question of
      whether PTED is a mental disorder of the post-traumatic type cannot be finally
      answered. It is not possible to specify an empirical criterion by means of which
      traumatic and non-traumatic life events can be differentiated. An empirical
      criterion for determining the traumatic nature of a given event depends on
      whether this event has already been classified as traumatic (i.e. circular
      argument). CONCLUSIONS: For the purpose of a clear classification of embitterment
      disorders, the new concept of adjustment disorders of Andreas Maercker and co
      workers is introduced. Based on the criteria and their findings, the best and
      most viable possibility to classify embitterment disorders in accordance with the
      current adjustment disorder and post-traumatic stress disorder definitions of ICD
      and DSM is by regarding embitterment disorders as a subtype of adjustment
      disorders.

PMID- 20148752
TI  - A case of Meniere's disease in the left ear and Lermoyez syndrome in the right
      ear--a 32-month longitudinal observation and literature review.
AB  - We here present a 32-month follow-up of a case of Lermoyez syndrome combined with
      Meniere's disease. The patient was a 49-year-old male, with a stabilized severe
      hearing loss in the left ear for about 15 years after Meniere's disease. He
      started to show typical symptoms of Lermoyez syndrome in the right ear about 32
      months ago. Audiologic data were obtained and imaging examinations were performed
      0, 9, 15, 28, and 32 months after the onset of the Lermoyez syndrome. Pure tone
      threshold data obtained 5 months before the onset are also reported. The results
      show that the hearing thresholds, mainly at low frequencies, elevated rapidly
      during the first months shortly after the onset of the disease and slowly in
      later months. The glycerol test resulted in a remarkable hearing improvement at
      the beginning of the disease, but showed no detectable improvements as the
      disease advanced. Electrocochleogram revealed a -SP/AP value with click stimulus
      0.65 at the 9th month and > 1.0 at the 28th month after the onset. Clinical
      manifestations of this patient fit well with a pathological endolymphatic
      hydrops.

PMID- 20148751
TI  - The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for
      the Biological Treatment of Bipolar Disorders: Update 2010 on the treatment of
      acute bipolar depression.
AB  - OBJECTIVES: These guidelines are based on a first edition that was published in
      2002, and have been edited and updated with the available scientific evidence
      until September 2009. Their purpose is to supply a systematic overview of all
      scientific evidence pertaining to the treatment of acute bipolar depression in
      adults. METHODS: The data used for these guidelines have been extracted from a
      MEDLINE and EMBASE search, from the clinical trial database clinicaltrials.gov,
      from recent proceedings of key conferences, and from various national and
      international treatment guidelines. Their scientific rigor was categorised into
      six levels of evidence (A-F). As these guidelines are intended for clinical use,
      the scientific evidence was finally assigned different grades of recommendation
      to ensure practicability. RESULTS: We identified 10 pharmacological monotherapies
      or combination treatments with at least limited positive evidence for efficacy in
      bipolar depression, several of them still experimental and backed up only by a
      single study. Only one medication was considered to be sufficiently studied to
      merit full positive evidence. CONCLUSIONS: Although major advances have been made
      since the first edition of this guideline in 2002, there are many areas which
      still need more intense research to optimize treatment. The majority of treatment
      recommendations is still based on limited data and leaves considerable areas of
      uncertainty.

PMID- 20148753
TI  - Proteomic analysis of formalin-fixed celloidin-embedded whole cochlear and laser
      microdissected spiral ganglion tissues.
AB  - CONCLUSION: The results of this study demonstrate that proteomic analysis can be
      successfully performed on formalin-fixed celloidin-embedded (FFCE) archival human
      cochlear tissues. OBJECTIVE: To investigate the feasibility of analyzing protein
      expression in archival cochlear tissues. MATERIAL AND METHODS: A new methodology,
      referred to as Liquid Tissue(TM), was used to extract proteins from human
      cochlear tissue sections and spiral ganglion tissue isolated by laser
      microdissection (LMD). Protein identification was performed by bioinformatic
      analysis of high resolution tandem mass spectrometric data from fractionated
      tryptic peptide samples. RESULTS: Twenty-six proteins were identified with a
      minimum of 2 unique peptides and 450 proteins were identified with 1 unique
      peptide at a confidence level of 95% in cochlear tissue. Ten proteins were
      identified with a minimum of 2 unique peptides and 485 proteins were identified
      with 1 unique peptide at a confidence level of 95% in spiral ganglion tissue.

PMID- 20148754
TI  - Thermophilic anaerobic digestion: the best option for waste treatment.
AB  - After introducing thermophilic anaerobic digestion (AD), characteristics of
      thermophilic methanogens are provided. Accordingly, (a) site of occurrence, (b)
      morphological characteristics (shape and motility), (c) biochemical
      characteristics (Gram character and % G+C profile), (d) nutritional
      characteristics (NaCl requirement and substrate specificity), and (e) growth
      characteristics (pH and temperature) of thermophilic methanogens are described.
      Some studies of the thermophilic AD are cited with their operational management
      problems. Subsequently, strategies to maximize net energy production are given,
      including mode of heating the bioreactors, role of agitation to promote AD
      performance and mode/intensity of mixing. Finally, advantages as well as
      drawbacks of AD under thermophilic conditions are given, concluding with its
      applications.

PMID- 20148755
TI  - Biorefinery of waste orange peel.
AB  - Up to comparatively recently orange peel and the associated residual remnants of
      membranes resulting from juice extraction represented a significant disposal
      problem, especially in those regions where orange cultivation is a major
      industry. However, recent research has demonstrated that orange peel waste
      represents a potentially valuable resource that can be developed into high value
      products. These developments are critically reviewed in this article. This
      includes a summary of the chemical composition of the substrate and an assessment
      of the range of applications in which the peel is deployed. Utilization as a
      substrate to produce animal feed, fertilizer, essential oils, pectin, ethanol,
      methane, industrial enzymes, and single cell protein is discussed. The
      applications described together with those that will no doubt be developed in the
      future, represent great opportunities to harness the economical benefit of this
      agro-industrial waste and to develop even more efficient and sustainable systems.
      A scheme of integrated utilization of orange peel in a biorefinery approach is
      discussed together with some prediction of further necessary research.

PMID- 20148756
TI  - Rituximab in relapsed aggressive lymphoma: play it again, Sam?

PMID- 20148757
TI  - Intensive therapies for mantle cell lymphoma: time for a disease-specific
      approach?

PMID- 20148758
TI  - Failure of molecular diagnostics in chronic myeloid leukemia: an aberrant form of
      e13a2 BCR-ABL transcript causing false-negative results by standard polymerase
      chain reaction.

PMID- 20148759
TI  - Notch regulates the generation of diverse cell types from the lateral lineage of
      Drosophila antennal lobe.
AB  - Diverse neuronal cell types arise from the lateral neuroblast in the antennal
      lobe of Drosophila. The authors show that loss of Notch function from the entire
      lineage during development leads to an absence of local interneurons (LNs) with a
      concomitant increase in the number of projection neurons (PNs). The presence of
      the intracellular domain of Notch was observed within the nucleus of newly born
      neurons within the neuroblast lineage. This leads to the suggestion that Notch
      acts in a binary fate decision to determine formation of LNs and PNs, resulting
      in two distinct hemilineages from the single neuroblast. The observation of
      nuclear Notch in several neuroblast lineages leads us to speculate that this
      mechanism is widespread during the developing Drosophila brain.

PMID- 20148760
TI  - Clinical PET imaging of insulinoma and beta-cell hyperplasia.
AB  - Persistent hyperinsulinemic hypoglycemia (PHH) is caused by solitary benign
      insulinoma or hyperplasia of pancreatic beta cells. In infants, PHH is caused by
      functionally defective hyperplastic beta cells, which are either diffusely or
      focally distributed in the pancreas. In adults, insulinoma is the most common
      cause of PHH, but recently, an increasing number of beta-cell hyperplasias has
      been reported among adults. The cause of adult beta-cell hyperplasia is not
      known. Whether the increased use of bariatric surgery in the treatment of severe
      obesity plays a role here is under investigation. Accurate localization of
      disease focus in both insulinoma and focal beta-cell hyperplasia provides an
      important support for surgery, especially as the use of laparoscopic surgery has
      increased. Conventional imaging of these challenging pancreatic lesions has
      evolved during recent years, but current imaging methods still lack sufficient
      sensitivity or are invasive. In most pancreatic NETs, the usefulness of positron
      emission tomography (PET) with fluorine-labeled fluorodeoxyglucose ([(18)F]FDG)
      for lesion detection is limited because of the low glucose turnover of these
      tumors. Based on the capacity of pancreatic beta cells to take up and
      decarboxylate amine precursors, several investigators have studied patients with
      pancreatic NETs using aminoacid precursors, such as [(18)F]dihydroxyphenylalanine
      (DOPA) and [(11)C]hydroxytryptophan (5-HTP), in an attempt to increase the
      sensitivity of PET scanning. Another characteristic of NETs is the expression of
      somatostatin receptors, and thus encouraging studies with somatostatin receptor
      imaging with [(18)Ga]-labeled somatostatin analogs have emerged as a new
      interesting imaging tool for the diagnosis of pancreatic NETs. This article
      provides an overview of our experiences and the current literature on PET imaging
      in patients with PHH caused by insulinoma or beta-cell hyperplasia.

PMID- 20148763
TI  - Trends in midlevel provider utilization.

PMID- 20148761
TI  - Co-segregation of AMPA receptors with G(M1) ganglioside in synaptosomal membrane
      subfractions.
AB  - Biochemical studies have suggested that certain synaptic proteins associate with
      lipid rafts to perform key functions within the synapse. However, variability in
      biochemical preparations raises questions as to which synaptic proteins actually
      associate with lipid rafts. In the present study, we use both electron microscopy
      and biochemistry to investigate AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid) receptor localization in synaptic membrane subfractions prepared
      in two different ways, by Triton X-100 detergent treatment or without detergent
      by sonication at high pH. Immunogold electron microscopy shows that a detergent
      resistant synaptosomal membrane subfraction consists of empty vesicles 0.1-1.0
      microm in diameter. A subpopulation of these vesicles labelled for
      glycosphingolipid GM1 ganglioside, a marker of lipid rafts, and 46% of the
      labelled vesicles also labelled for the AMPA receptor subunit GluR2. This co
      segregation into specific vesicles does not depend on effects of detergent
      because a similar distribution of label was found in vesicles isolated without
      the use of detergent. Our results suggest that AMPA receptors localize within
      specific regions of synaptic membranes rich in GM1 ganglioside.

PMID- 20148764
TI  - Regarding "can unannounced standardized patients assess...".

PMID- 20148767
TI  - Emergency ultrasound identification of loculated pericardial effusion: the
      importance of multiple cardiac views.

PMID- 20148768
TI  - Superior labial artery aneurysm after mouth laceration.

PMID- 20148769
TI  - The Robert Wood Johnson Foundation Clinical Scholars Program and emergency
      medicine.
AB  - Specialized research training for emergency physicians (EPs) may strengthen
      overall patient care through the development and improvement of clinical evidence
      in emergency care. One way an increasing number of emergency physicians have
      acquired these skills is through the Robert Wood Johnson Foundation Clinical
      Scholars Program (CSP), a 2-year fellowship that trains physicians to be leaders
      in improving health care. In addition to providing training in health policy and
      health services research, the CSP emphasizes the translation of research into
      action through leadership training, program development, and community-based
      participatory research. This article provides an in-depth look at the CSP and its
      impact on emergency medicine (EM). To date, 41 EPs have trained through the
      program, with increasing numbers in recent years. Graduates have gone on to
      become leaders in academia, public health, private industry, and foundations.
      Past and present EM-trained Clinical Scholars are working to find creative
      solutions for the challenges posed by the U.S. health care system and improve the
      delivery of emergency care. Emergency physicians who wish to conduct research or
      work with communities, organizations, practitioners, and policy-makers to address
      issues essential to the health and well-being of all Americans should consider
      the Robert Wood Johnson Foundation CSP.

PMID- 20148770
TI  - A case report of systemic capillary leak syndrome (Clarkson's disease).
AB  - Systemic capillary leak syndrome (SCLS) is a very rare disorder also known as
      Clarkson's disease. The condition is characterized by recurrent episodes of
      severe capillary hyperpermeability resulting in severe hemoconcentration,
      hypoalbuminemia, hypovolemia and shock. We describe a 41-year-old previously
      healthy man who was admitted to hospital on several occasions with rapidly
      developing hypovolemic shock accompanied by extreme hemoconcentration and
      hypoalbuminemia. Our case is similar to other reports describing patients with
      SCLS where the initial suspicions have been pointing towards septic shock. He
      received a combination of prophylactic treatment with theophylline, beta
      agonists, immunoglobulins and statins but eventually died after a severe episode
      of SCLS that ended with recurrent cardiac arrest. Clinical autopsy revealed
      pulmonary edema and acute and chronical organic fluid overload. SCLS should be
      kept in mind when treating patients suffering from attacks of severe idiopathic
      edema and mimics recurrent septic shock where no pathogen is found. The
      pathogenesis is unknown and the attacks may be lethal.

PMID- 20148771
TI  - Reduced interleukin-12 release from stimulated monocytes in patients with sepsis
      after major cancer surgery.
AB  - BACKGROUND: Major cancer surgery is a high-risk situation for sepsis in the post
      operative period. The aim of this study was to assess the relation between the
      monocyte production of IL-12 and the development of post-operative sepsis in
      patients undergoing major cancer surgery. METHODS: In 19 patients undergoing
      major cancer surgery, the production of cytokines by basal and lipolysaccharide
      (LPS)-stimulated monocytes was measured before and after (from day 1 to day 3 and
      day 7) surgery. Seven of them developed a post-operative sepsis. Ten healthy
      volunteers were used as controls for the assessment of pre-operative values.
      RESULTS: Before surgery, the production of interleukin (IL)-12 p40 by LPS
      stimulated monocytes was similar in the patients and the healthy volunteers. The
      production of IL-12 p40 by unstimulated monocytes was higher in the patients than
      in the healthy volunteers. IL-12 production did not differ between the septic and
      the non-septic patients. After surgery, the production of IL-12 p40 was
      dramatically reduced in the LPS-stimulated monocytes of the septic patients from
      day 1 to day 3, as compared with that of the non-septic patients. Before surgery,
      the production of IL-6, IL-10, and IL-1 receptor antagonist (IL-1ra) in the
      patients was significantly higher than that of the healthy volunteers for both
      stimulated and unstimulated monocytes. After surgery, the production of these
      cytokines by both stimulated and unstimulated monocytes of the septic patients
      was similar to that of the non-septic patients. Intragroup analysis showed
      significant changes for IL-6, IL-10, and IL-1ra under all conditions, with the
      exception of changes in unstimulated monocytes of septic patients that were not
      significant for IL-10 release. CONCLUSION: After surgery, the septic patients
      showed drastic failure to up-regulate monocyte LPS-stimulated production of IL-12
      p40.

PMID- 20148772
TI  - Spectral entropy monitoring allowed lower sevoflurane concentration and faster
      recovery in children.
AB  - BACKGROUND: Anesthetic titration using spectral entropy monitoring reduces
      anesthetic requirements and shortens recovery in adult surgical patients. This
      study was performed to evaluate the effect of entropy monitoring on end-tidal
      sevoflurane concentration and recovery characteristics in pediatric patients
      undergoing sevoflurane anesthesia. METHODS: Seventy-eight children (aged 3-12
      years) scheduled for a tonsillectomy and/or an adenoidectomy were randomly
      divided into one of two groups: standard practice (Standard) or entropy-guided
      (Entropy). In the Standard group, sevoflurane was adjusted to maintain the heart
      rate and systolic blood pressure (BP) within 20% of the baseline values. In the
      Entropy group, sevoflurane was adjusted to achieve a state entropy of 40-50. We
      compared the entropy values, end-tidal sevoflurane concentration and recovery
      times between groups. RESULTS: During maintenance of anesthesia, the entropy and
      BP values were higher in the Entropy group (P<0.05). The end-tidal sevoflurane
      concentration during maintenance was lower in the Entropy group (2.2 (0.3) vol%)
      compared with the Standard group (2.6 (0.4) vol%) (P<0.05). Recovery times were
      faster in the Entropy group (P<0.05). CONCLUSIONS: Compared with standard
      practice, we found that entropy-guided anesthetic administration was associated
      with a reduced sevoflurane concentration and a slightly faster emergence and
      recovery in 3-12-year-old children.

PMID- 20148773
TI  - Remembering the lost neuroscience of pharmaco-EEG.

PMID- 20148774
TI  - Consilience of rodent and human phenotypes relevant for alcohol dependence.

PMID- 20148775
TI  - Ethanol consumption: how should we measure it? Achieving consilience between
      human and animal phenotypes.
AB  - There is only modest overlap in the most common alcohol consumption phenotypes
      measured in animal studies and those typically studied in humans. To address this
      issue, we identified a number of alcohol consumption phenotypes of importance to
      the field that have potential for consilience between human and animal models.
      These phenotypes can be broken down into three categories: (1) abstinence/the
      decision to drink or abstain; (2) the actual amount of alcohol consumed; and (3)
      heavy drinking. A number of suggestions for human and animal researchers are made
      in order to address these phenotypes and enhance consilience. Laboratory studies
      of the decision to drink or to abstain are needed in both human and animal
      research. In human laboratory studies, heavy or binge drinking that meets cut
      offs used in epidemiological and clinical studies should be reported. Greater
      attention to patterns of drinking over time is needed in both animal and human
      studies. Individual differences pertaining to all consumption phenotypes should
      be addressed in animal research. Lastly, improved biomarkers need to be developed
      in future research for use with both humans and animals. Greater precision in
      estimating blood alcohol levels in the field, together with consistent
      measurement of breath/blood alcohol levels in human laboratory and animal
      studies, provides one means of achieving greater consilience of alcohol
      consumption phenotypes.

PMID- 20148777
TI  - Reward sensitivity: issues of measurement, and achieving consilience between
      human and animal phenotypes.
AB  - Reward is a concept fundamental to discussions of drug abuse and addiction. The
      idea that altered sensitivity to either drug-reward, or to rewards in general,
      contributes to, or results from, drug-taking is a common theme in several
      theories of addiction. However, the concept of reward is problematic in that it
      is used to refer to apparently different behavioural phenomena, and even to
      diverse neurobiological processes (reward pathways). Whether these different
      phenomena are different behavioural expressions of a common underlying process is
      not established, and much research suggests that there may be only loose
      relationships among different aspects of reward. Measures of rewarding effects of
      drugs in humans often depend upon subjective reports. In animal studies, such
      insights are not available, and behavioural measures must be relied upon to infer
      rewarding effects of drugs or other events. In such animal studies, but also in
      many human methods established to objectify measures of reward, many other
      factors contribute to the behaviour being studied. For that reason, studying the
      biological (including genetic) bases of performance of tasks that ostensibly
      measure reward cannot provide unequivocal answers. The current overview outlines
      the strengths and weaknesses of current approaches that hinder the conciliation
      of cross-species studies of the genetics of reward sensitivity and the
      dysregulation of reward processes by drugs of abuse. Some suggestions are made as
      to how human and animal studies may be made to address more closely homologous
      behaviours, even if those processes are only partly able to isolate 'reward' from
      other factors contributing to behavioural output.

PMID- 20148776
TI  - Human and laboratory rodent low response to alcohol: is better consilience
      possible?
AB  - If people are brought into the laboratory and given alcohol, there are pronounced
      differences among individuals in many responses to the drug. Some participants in
      alcohol challenge protocols show a cluster of 'low level of responses to alcohol'
      determined by observing post-drinking-related changes in subjective, motor and
      physiological effects at a given dose level. Those individuals characterized as
      having low level of response (LR) to alcohol have been shown to be at increased
      risk for a lifetime diagnosis of alcohol dependence (AD), and this relationship
      between low LR and AD appears to be in part genetic. LR to alcohol is an area
      where achieving greater consilience between the human and the rodent phenotypes
      would seem to be highly likely. However, despite extensive data from both human
      and rodent studies, few attempts have been made to evaluate the human and animal
      data systematically in order to understand which aspects of LR appear to be most
      directly comparable across species and thus the most promising for further study.
      We review four general aspects of LR that could be compared between humans and
      laboratory animals: (1) behavioral measures of subjective intoxication; (2) body
      sway; (3) endocrine responses; and (4) stimulant, autonomic and
      electrophysiological responses. None of these aspects of LR provide completely
      face-valid direct comparisons across species. Nevertheless, one of the most
      replicated findings in humans is the low subjective response, but, as it may
      reflect either aversively valenced and/or positively valenced responses to
      alcohol as usually assessed, it is unclear which rodent responses are analogous.
      Stimulated heart rate appears to be consistent in animal and human studies,
      although at-risk subjects appear to be more rather than less sensitive to alcohol
      using this measure. The hormone and electrophysiological data offer strong
      possibilities of understanding the neurobiological mechanisms, but the rodent
      data in particular are rather sparse and unsystematic. Therefore, we suggest that
      more effort is still needed to collect data using refined measures designed to be
      more directly comparable in humans and animals. Additionally, the genetically
      mediated mechanisms underlying this endophenotype need to be characterized
      further across species.

PMID- 20148778
TI  - Acute withdrawal, protracted abstinence and negative affect in alcoholism: are
      they linked?
AB  - The role of withdrawal-related phenomena in the development and maintenance of
      alcohol addiction remains under debate. A 'self-medication' framework postulates
      that emotional changes are induced by a history of alcohol use, persist into
      abstinence, and are a major factor in maintaining alcoholism. This view initially
      focused on negative emotional states during early withdrawal: these are
      pronounced, occur in the vast majority of alcohol-dependent patients, and are
      characterized by depressed mood and elevated anxiety. This concept lost
      popularity with the realization that in most patients, these symptoms abate over
      3-6 weeks of abstinence, while relapse risk persists long beyond this period.
      More recently, animal data have established that a prolonged history of alcohol
      dependence induces more subtle neuroadaptations. These confer altered emotional
      processing that persists long into protracted abstinence. The resulting
      behavioral phenotype is characterized by excessive voluntary alcohol intake and
      increased behavioral sensitivity to stress. Emerging human data support the
      clinical relevance of negative emotionality for protracted abstinence and
      relapse. These developments prompt a series of research questions: (1) are
      processes observed during acute withdrawal, while transient in nature,
      mechanistically related to those that remain during protracted abstinence?; (2)
      is susceptibility to negative emotionality in acute withdrawal in part due to
      heritable factors, similar to what animal models have indicated for
      susceptibility to physical aspects of withdrawal?; and (3) to what extent is
      susceptibility to negative affect that persists into protracted abstinence
      heritable?

PMID- 20148779
TI  - A comparison of selected quantitative trait loci associated with alcohol use
      phenotypes in humans and mouse models.
AB  - Evidence for genetic linkage to alcohol and other substance dependence phenotypes
      in areas of the human and mouse genome have now been reported with some
      consistency across studies. However, the question remains as to whether the genes
      that underlie the alcohol-related behaviors seen in mice are the same as those
      that underlie the behaviors observed in human alcoholics. The aims of the current
      set of analyses were to identify a small set of alcohol-related phenotypes in
      human and in mouse by which to compare quantitative trait locus (QTL) data
      between the species using syntenic mapping. These analyses identified that QTLs
      for alcohol consumption and acute and chronic alcohol withdrawal on distal mouse
      chromosome 1 are syntenic to a region on human chromosome 1q where a number of
      studies have identified QTLs for alcohol-related phenotypes. Additionally, a QTL
      on human chromosome 15 for alcohol dependence severity/withdrawal identified in
      two human studies was found to be largely syntenic with a region on mouse
      chromosome 9, where two groups have found QTLs for alcohol preference. In both of
      these cases, while the QTLs were found to be syntenic, the exact phenotypes
      between humans and mice did not necessarily overlap. These studies demonstrate
      how this technique might be useful in the search for genes underlying alcohol
      related phenotypes in multiple species. However, these findings also suggest that
      trying to match exact phenotypes in humans and mice may not be necessary or even
      optimal for determining whether similar genes influence a range of alcohol
      related behaviors between the two species.

PMID- 20148781
TI  - Understanding the construct of impulsivity and its relationship to alcohol use
      disorders.
AB  - There are well-established links between impulsivity and alcohol use in humans
      and other model organisms; however, the etiological nature of these associations
      remains unclear. This is likely due, in part, to the heterogeneous nature of the
      construct of impulsivity. Many different measures of impulsivity have been
      employed in human studies, using both questionnaire and laboratory-based tasks.
      Animal studies also use multiple tasks to assess the construct of impulsivity. In
      both human and animal studies, different measures of impulsivity often show
      little correlation and are differentially related to outcome, suggesting that the
      impulsivity construct may actually consist of a number of more homogeneous (and
      potentially more meaningful) subfacets. Here, we provide an overview of the
      different measures of impulsivity used across human and animal studies, evidence
      that the construct of impulsivity may be better studied in the context of more
      meaningful subfacets, and recommendations for how research in this direction may
      provide for better consilience between human and animal studies of the connection
      between impulsivity and alcohol use.

PMID- 20148780
TI  - Consilient research approaches in studying gene x environment interactions in
      alcohol research.
AB  - This review article discusses the importance of identifying gene-environment
      interactions for understanding the etiology and course of alcohol use disorders
      and related conditions. A number of critical challenges are discussed, including
      the fact that there is no organizing typology for classifying different types of
      environmental exposures, many key human environmental risk factors for alcohol
      dependence have no clear equivalents in other species, much of the genetic
      variance of alcohol dependence in human is not 'alcohol specific', and the
      potential range of gene-environment interactions that could be considered is so
      vast that maintaining statistical control of Type 1 errors is a daunting task.
      Despite these and other challenges, there appears to be a number of promising
      approaches that could be taken in order to achieve consilience and ecologically
      valid translation between human alcohol dependence and animal models. Foremost
      among these is to distinguish environmental exposures that are thought to have
      enduring effects on alcohol use motivation (and self-regulation) from situational
      environmental exposures that facilitate the expression of such motivations but do
      not, by themselves, have enduring effects. In order to enhance consilience,
      various domains of human approach motivation should be considered so that
      relevant environmental exposures can be sampled, as well as the appropriate
      species to study them in (i.e. where such motivations are ecologically relevant).
      Foremost among these are social environments, which are central to the initiation
      and escalation of human alcohol consumption. The value of twin studies, human
      laboratory studies and pharmacogenetic studies is also highlighted.

PMID- 20148782
TI  - Modeling missing binary outcome data in a successful web-based smokeless tobacco
      cessation program.
AB  - AIM: To examine various methods to impute missing binary outcome from a web-based
      tobacco cessation intervention. DESIGN: The ChewFree randomized controlled trial
      used a two-arm design to compare tobacco abstinence at both the 3- and 6-month
      follow-up for participants randomized to either an enhanced web-based
      intervention condition or a basic information-only control condition. SETTING:
      Internet in the United States and Canada. PARTICIPANTS: Secondary analyses
      focused upon 2523 participants in the ChewFree trial. MEASUREMENTS: Point
      prevalence tobacco abstinence measured at 3- and 6-month follow-up. FINDINGS: The
      results of this study confirmed the findings for the original ChewFree trial and
      highlighted the use of different missing-data approaches to achieve intent-to
      treat analyses when confronted with substantial attrition. The use of different
      imputation methods yielded results that differed in both the size of the
      estimated treatment effect and the standard errors. CONCLUSIONS: The choice of
      imputation model used to analyze missing binary outcome data can affect
      substantially the size and statistical significance of the treatment effect.
      Without additional information about the missing cases, they can overestimate the
      effect of treatment. Multiple imputation methods are recommended, especially
      those that permit a sensitivity analysis of their impact.

PMID- 20148783
TI  - Human sex differences in d-amphetamine self-administration.
AB  - Women and men may respond differently to the effects of stimulants such as
      amphetamine and cocaine. AIM: In order to assess potential sex differences in the
      reinforcing effects of d-amphetamine, a retrospective-analysis was conducted on
      data collected from three studies that employed similar d-amphetamine self
      administration procedures and used identical subject-rated drug-effect measures.
      METHODS: Data from 10 women and 15 men were included in the analysis. In all
      studies, participants sampled placebo, low (8-10 mg) or high (16-20 mg) dose oral
      d-amphetamine. Following sampling sessions, participants worked for capsules
      containing one eighth of the previously sampled dose on a modified progressive
      ratio schedule of reinforcement. We hypothesized that women and men would be
      differentially sensitive to the reinforcing effects of d-amphetamine. A two-way
      mixed-model analysis of variance (sex and dose) and planned comparisons were used
      in the statistical analyses. RESULTS: The low dose of d-amphetamine functioned as
      a reinforcer in women, but not men, whereas the high dose of d-amphetamine
      functioned as a reinforcer in men, but not women. Men self-administered
      significantly more capsules under the high dose condition than women. CONCLUSION:
      The results of this study suggest that men are more sensitive to the reinforcing
      effects of a high dose of d-amphetamine than women. Future research is needed
      that determines prospectively the reinforcing effects of weight-adjusted doses of
      d-amphetamine in women and men while controlling for menstrual cycle phase.

PMID- 20148784
TI  - Characteristics and comorbidity of drug and alcohol-related emergency department
      presentations detected by nursing triage text.
AB  - INTRODUCTION: This study used nursing triage text to detect drug- and alcohol
      related emergency department (ED) presentations and describe their patient and
      service delivery characteristics. METHODS: Data were reviewed for all ED
      presentations from 2004 to 2006 (n = 263 937) from two hospitals in Sydney,
      Australia. Each record included two nursing triage free-text fields, which were
      searched for more than 100 drug-related and more than 60 alcohol-related terms.
      Adjusted odds ratios were used to compare the characteristics of drug and alcohol
      related ED presentations with all other ED presentation types. RESULTS: Just over
      5% of ED presentations were identified as alcohol-related and 2% as drug-related.
      The most prevalent drug-related ED presentations specified were related to
      amphetamines (18%), heroin (14%), cannabis (14%) and ecstasy (12%), while nearly
      half (43%) were drug unspecified. Polydrug use was mentioned in 25% of drug
      related and 9% of alcohol-related ED presentations, with the highest rate of
      polydrug use among ecstasy-related (68%) presentations. Drug- and alcohol-related
      ED presentations were significantly more likely than other ED presentations to
      have a mental health diagnosis, with the highest rates found among cannabis
      related (OR = 7.6) or amphetamine-related (OR = 7.5) presentations. CONCLUSION:
      The ED provides an opportunity for early intervention for patients presenting
      with comorbid drug and alcohol and mental health problems. Further research is
      needed to assess the prevalence of drug and alcohol problems in ED patients with
      mental health problems and to develop effective interventions in that setting.

PMID- 20148785
TI  - Symptoms of nicotine dependence in a cohort of Swedish youths: a comparison
      between smokers, smokeless tobacco users and dual tobacco users.
AB  - AIMS: To determine whether symptoms of nicotine dependence, addiction and
      withdrawal symptoms differ between exclusive smokers, exclusive snus (moist
      snuff) users and dual users. DESIGN: A cross-sectional survey of a cohort
      subsample. Setting County of Stockholm, Sweden. PARTICIPANTS: Current exclusive
      smokers (n = 466), exclusive snus users (n = 209) and dual users (n = 144), mean
      age 17.6 years. MEASUREMENTS: Self-reported life-time experience of nicotine
      dependence and withdrawal symptoms in periods of discontinued tobacco use.
      Selected items from the modified Fagerstom Tolerance Questionnaire (mFTQ), the
      Hooked on Nicotine Checklist (HONC) and the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV). FINDINGS: The odds ratio of endorsing each of four
      mFTQ items as well as the HONC item investigating the risk of feeling addicted to
      tobacco was two to five-fold higher for exclusive snus users and for dual users
      compared to exclusive smokers. One DSM-IV item (difficult to refrain from use)
      was elevated among dual users compared to smokers. Dual users reported the
      highest prevalence of any withdrawal symptom in contrast to exclusive snus users,
      who reported a lower risk of withdrawal symptoms compared to exclusive smokers.
      CONCLUSIONS: Smokeless tobacco users show symptoms of nicotine dependence at
      least as frequently as cigarette smokers. Symptoms of nicotine dependence and of
      withdrawal during quit attempts are particularly frequent in the subgroup of
      users who combine smokeless tobacco with smoking.

PMID- 20148786
TI  - Substance use and periodontal disease among Australian Aboriginal young adults.
AB  - AIM: To investigate the effects of tobacco, marijuana, alcohol and petrol
      sniffing on periodontal disease among Australian Aboriginal young adults. DESIGN:
      Cross-sectional nested within a long-standing prospective longitudinal study.
      Setting Aboriginal communities in Australia's Northern Territory. PARTICIPANTS:
      Members of the Aboriginal Birth Cohort study who were recruited from birth
      between January 1987 and March 1990 at the Royal Darwin Hospital, Northern
      Territory, Australia. Data were from wave III, when the mean age of participants
      was 18 years. MEASUREMENTS: Clinical dental examination and self-report
      questionnaire. FINDINGS: Of 425 participants with complete data, 26.6% had
      moderate/severe periodontal disease. There was elevated risk of periodontal
      disease associated with tobacco [prevalence ratio (PR) = 1.59, 95% CI = 1.06
      2.40], marijuana (PR = 1.44, 95% CI = 1.05-1.97) and petrol sniffing (PR = 1.83,
      95% CI = 1.08-3.11), but not alcohol (PR = 0.92, 95% CI = 0.67-1.27). Stratified
      analysis showed that the effect of marijuana persisted among tobacco users (PR =
      1.47, 95% CI 1.03-2.11). It was not possible to isolate an independent effect of
      petrol sniffing because all petrol sniffers used both marijuana and tobacco,
      although among smokers of both substances, petrol sniffing was associated with an
      11.8% increased prevalence of periodontal disease. CONCLUSIONS: This is the first
      time that substance use has been linked with periodontal disease in a young
      Australian Aboriginal adult population, and the first time that petrol sniffing
      has been linked with periodontal disease in any population. The role of substance
      use in periodontal disease among this, and other, marginalized groups warrants
      further investigation.

PMID- 20148787
TI  - Three-year mortality and predictors after release: a longitudinal study of the
      first-time drug offenders in Taiwan.
AB  - AIMS: To assess the possible increase in mortality rate and associated socio
      demographic and judiciary determinants among first-time drug offenders during the
      first 3 years after release from correctional facilities. SETTING AND
      PARTICIPANTS: A total of 22 224 male and 4444 female adults who had served a
      sentence of at least 1 day in correctional facilities for illegal drug-related
      offences were identified from the judiciary records of the Ministry of Justice,
      Taiwan. DESIGN AND MEASUREMENTS: The underlying causes of death were defined by
      the International Classification of Diseases, ninth revision. Findings All-cause
      standardized mortality ratios (SMR) were 7 for schedule I (e.g. heroin) and 3 for
      schedule II (e.g. methamphetamine) drug offenders, respectively; accidents,
      suicide and circulatory diseases were three leading causes of death. After
      release, the risk of death among those drug offenders without subsequent
      incarceration increased gradually until the 9th month. Those who were aged 30
      years or older, had an engagement with a higher-ranked schedule substance or who
      received severe sentences were two to three times more likely to die. Substantial
      reduction in the risk of death was linked with re-imprisonment. CONCLUSIONS: The
      SMR estimates for external causes were greater than those for disease-related
      causes in drug offenders, and schedule I drugs-related mortality rate was twice
      as high as that with schedule II drugs. In transitioning from the correctional
      setting to the community, the health needs of drug offenders should be addressed
      by the provision of continuous, adequate medical care tailored to individual
      background, medical history and drug experience.

PMID- 20148788
TI  - Comparative rates of violent crime among regular methamphetamine and opioid
      users: offending and victimization.
AB  - AIMS: To determine the comparative levels of violent offending and victimization
      among regular methamphetamine and heroin users. DESIGN: Cross-sectional Setting
      Sydney, Australia. PARTICIPANTS: A total of 400 regular methamphetamine (METH)
      and heroin (HER) users (118 methamphetamine users: METH; 161 regular heroin
      users: HER; 121 regular users of both: BOTH). FINDINGS: Eighty-two per cent
      reported a life-time history of committing violent crime, 41% in the past 12
      months. There were no group differences in life-time violence, but the METH group
      were significantly more likely than the HER group to have committed violence in
      the past 12 months (odds ratio 1.94). Nearly all (95%) reported that they had
      been a victim of violent crime, 46% in the preceding 12 months, with no group
      differences. Those who had committed a violent crime in the past 12 months were
      13.23 times more likely to have been a victim in that period. The majority
      believed it unlikely that they would be a victim of (78%), or commit (87%), a
      violent crime in the next 12 months. CONCLUSIONS: Regular methamphetamine use
      appears to be associated with an increased risk of violent offending, but not
      victimization, compared with heroin use.

PMID- 20148789
TI  - Sweet preferences and analgesia during childhood: effects of family history of
      alcoholism and depression.
AB  - AIM: To determine whether depression and family history of alcoholism are
      associated with heightened sweet preferences in children, before they have
      experienced alcohol or tobacco and at a time during the life-span when sweets are
      particularly salient. Design Between- and within-subject experimental study.
      PARTICIPANTS: Children, 5-12 years old (n = 300), formed four groups based on
      family history of alcohol dependence up to second-degree relatives [positive
      (FHP) versus negative (FHN)] and depressive symptoms as determined by the
      Pictorial Depression Scale [depressed (PDEP) versus non-depressed (NDEP)].
      MEASUREMENTS: Children were tested individually to measure sucrose preferences,
      sweet food liking and, for a subset of the children, the analgesic properties of
      sucrose versus water during the cold pressor test. FINDINGS: The co-occurrence of
      having a family history of alcoholism and self-reports of depressive
      symptomatology was associated significantly with a preference for a more
      concentrated sucrose solution, while depressive symptomatology alone was
      associated with greater liking for sweet-tasting foods and candies and increased
      pain sensitivity. Depression antagonized the analgesic properties of sucrose.
      CONCLUSIONS: While children as a group innately like sweets and feel better after
      eating them, the present study reveals significant contributions of family
      history of alcoholism and depression to this effect. Whether the heightened sweet
      preference and the use of sweets to alleviate depression are markers for
      developing alcohol-related problems or responses that are protective are
      important areas for future research.

PMID- 20148790
TI  - The effect of image complexity on attentional bias towards alcohol-related images
      in adult drinkers.
AB  - AIM: Visual probe tasks are often used to measure attentional bias (AB) towards
      alcohol-related images in drinkers, but little is known about the effect of the
      properties of the images used in this task: specifically, image complexity.
      METHODS: AB was examined in a group of adult drinkers (n = 25). Two measures of
      attentional bias were obtained from a modified visual probe task. First, a
      traditional dot probe detection task measured attentional bias in drinkers based
      on their reaction times to probes replacing neutral and alcohol-related images.
      Secondly, an eye-tracking measure was applied to this task to directly assess the
      drinkers' eye gazes to the alcohol-related and neutral images. The effect of
      image complexity was examined by comparing AB towards images classified as simple
      and complex. FINDINGS: Results showed that drinkers displayed AB only towards
      simple alcohol-related images as measured by both probe RT and fixation times.
      CONCLUSION: These findings suggest that complex alcohol-related images might be
      less effective at capturing drinkers' attention and could result in less
      attentional bias when used in visual probe tasks.

PMID- 20148791
TI  - Internet-based prevention for alcohol and cannabis use: final results of the
      Climate Schools course.
AB  - AIMS: To establish the long-term efficacy of a universal internet-based alcohol
      and cannabis prevention programme in schools. METHODS: A cluster-randomized
      controlled trial was conducted to assess the effectiveness of the Climate
      Schools: Alcohol and Cannabis Course. The evidence-based course, aimed at
      reducing alcohol and cannabis use, is facilitated by the internet and consists of
      12 novel and curriculum consistent lessons delivered over 6 months. PARTICIPANTS:
      A total of 764 year 8 students (13 years) from 10 Australian secondary schools
      were allocated randomly to the internet-based prevention programme (n = 397, five
      schools), or to their usual health classes (n = 367, five schools). MEASURES:
      Participants were assessed at baseline, immediately post, and 6 and 12 months
      following completion of the intervention, on measures of alcohol and cannabis
      knowledge, attitudes, use and related harms. RESULTS: This paper reports the
      final results of the intervention trial, 12 months following the completion of
      the Climate Schools: Alcohol and Cannabis Course. The effectiveness of the course
      6 months following the intervention has been reported previously. At the 12-month
      follow-up, compared to the control group, students in the intervention group
      showed significant improvements in alcohol and cannabis knowledge, a reduction in
      average weekly alcohol consumption and a reduction in frequency of drinking to
      excess. No differences between groups were found on alcohol expectancies,
      cannabis attitudes or alcohol- and cannabis-related harms. The course was found
      to be acceptable by teachers and students as a means of delivering drug education
      in schools. CONCLUSIONS: Internet-based prevention programs for school-age
      children can improve student's knowledge about alcohol and cannabis, and may also
      reduce alcohol use twelve months after completion.

PMID- 20148792
TI  - How ideology shapes the evidence and the policy: what do we know about cannabis
      use and what should we do?
AB  - In the United Kingdom, as in many places, cannabis use is considered
      substantially within a criminal justice rather than a public health paradigm with
      prevention policy embodied in the Misuse of Drugs Act. In 2002 the maximum
      custodial sentence tariff for cannabis possession under the Act was reduced from
      5 to 2 years. Vigorous and vociferous public debate followed this decision,
      centred principally on the question of whether cannabis use caused schizophrenia.
      It was suggested that new and compelling evidence supporting this hypothesis had
      emerged since the re-classification decision was made, meaning that the decision
      should be reconsidered. The re-classification decision was reversed in 2008. We
      consider whether the strength of evidence on the psychological harms of cannabis
      has changed substantially and discuss the factors that may have influenced recent
      public discourse and policy decisions. We also consider evidence for other harms
      of cannabis use and public health implications of preventing cannabis use. We
      conclude that the strongest evidence of a possible causal relation between
      cannabis use and schizophrenia emerged more than 20 years ago and that the
      strength of more recent evidence may have been overstated--for a number of
      possible reasons. We also conclude that cannabis use is almost certainly harmful,
      mainly because of its intimate relation to tobacco use. The most rational policy
      on cannabis from a public health perspective would seem to be one able to achieve
      the benefit of reduced use in the population while minimizing social and other
      costs of the policy itself. Prohibition, whatever the sentence tariff associated
      with it, seems unlikely to fulfil these criteria.

PMID- 20148793
TI  - How much alcohol do you buy? A comparison of self-reported alcohol purchases with
      actual sales.
AB  - BACKGROUND: Unrecorded alcohol has increased in the Nordic countries during
      recent years, above all in terms of cross-border trade. This implies that trends
      and levels of per capita consumption would look different without estimates of
      this source of alcohol, estimates that in Sweden and other countries are made
      through surveys. AIM: The overall aim is to analyse the validity of Swedish
      survey estimates of alcohol bought in the cross-border trade and possibly to
      develop weights that can be applied to such estimates. DATA AND METHOD: The
      analysis consists of comparing self-reported purchases of spirits, wine,
      cider/alcopops and beer at retail monopoly (Systembolaget) during 2008 (n =
      18,000) with actual sales during the same period overall and monthly. FINDINGS:
      Of the recorded amount of purchases at Systembolaget, 87% was reported in the
      survey, compared with the 40-60% usually found for self-reported consumption.
      Significant differences across beverages were revealed, showing a lower coverage
      rate for beer and spirits and a higher coverage rate for wine and cider. Changes
      in purchases of all beverages were captured fairly well, at least changes taking
      place from one month to another. CONCLUSIONS: Self-reported alcohol purchases
      achieve a higher coverage rate than found typically in studies based on self
      reported use of alcohol. If adjustments are to be made to correct for
      underreporting in self-reported data on alcohol purchases, different weights
      should be applied to different beverages. Furthermore, at least major changes in
      how much alcohol is purchased in the population can be monitored using well
      designed population surveys.

PMID- 20148794
TI  - The impact of a supervised injecting facility on ambulance call-outs in Sydney,
      Australia.
AB  - AIMS: Supervised injecting facilities (SIFs) are effective in reducing the harms
      associated with injecting drug use among their clientele, but do SIFs ease the
      burden on ambulance services of attending to overdoses in the community? This
      study addresses this question, which is yet to be answered, in the growing body
      of international evidence supporting SIFs efficacy. DESIGN: Ecological study of
      patterns in ambulance attendances at opioid-related overdoses, before and after
      the opening of a SIF in Sydney, Australia. SETTING: A SIF opened as a pilot in
      Sydney's 'red light' district with the aim of accommodating a high throughput of
      injecting drug users (IDUs) for supervised injecting episodes, recovery and the
      management of overdoses. MEASUREMENTS: A total of 20,409 ambulance attendances at
      opioid-related overdoses before and after the opening of the Sydney SIF. Average
      monthly ambulance attendances at suspected opioid-related overdoses, before (36
      months) and after (60 months) the opening of the Sydney Medically Supervised
      Injecting Centre (MSIC), in the vicinity of the centre and in the rest of New
      South Wales (NSW). RESULTS: The burden on ambulance services of attending to
      opioid-related overdoses declined significantly in the vicinity of the Sydney SIF
      after it opened, compared to the rest of NSW. This effect was greatest during
      operating hours and in the immediate MSIC area, suggesting that SIFs may be most
      effective in reducing the impact of opioid-related overdose in their immediate
      vicinity. CONCLUSIONS: By providing environments in which IDUs receive supervised
      injection and overdose management and education SIF can reduce the demand for
      ambulance services, thereby freeing them to attend other medical emergencies
      within the community.

PMID- 20148795
TI  - How does variability in alcohol consumption over time affect the relationship
      with mortality and coronary heart disease?
AB  - OBJECTIVE: To examine the relationship between alcohol consumption and risk of
      mortality and incident coronary heart disease (CHD), taking account of variation
      in intake during follow-up. METHOD: Prospective cohort study of 5411 male civil
      servants aged 35-55 years at entry to the Whitehall II study in 1985-88. Alcohol
      consumption was reported five times over a 15-year period. Mortality, fatal CHD,
      clinically verified incident non-fatal myocardial infarction and definite angina
      were ascertained during follow-up. RESULTS: We found evidence that drinkers who
      vary their intake during follow-up, regardless of average level, have increased
      risk of total mortality (hazard ratio of high versus low variability 1.52: 95%
      CI: 1.07-2.17), but not of incident CHD. Using average consumption level, as
      opposed to only a baseline measure, gave slightly higher risk estimates for CHD
      compared to moderate drinkers at the extremes of the drinking range. CONCLUSIONS:
      Multiple repeated measures are required to explore the effects of variation in
      exposure over time. Caution is needed when interpreting risks of exposures
      measured only once at baseline, without consideration of changes over time.

PMID- 20148796
TI  - Drug classification: science, politics, both or neither?
AB  - Governments currently classify illicit drugs for various purposes: to guide
      courts in the sentencing of convicted violators of drug control laws, to
      prioritize targets of prevention measures and to educate the public about
      relative risks of the various drugs. It has been proposed that classification
      should be conducted by scientists and drug experts rather than by politicians, so
      that it will reflect only accurate factual knowledge of drug effects and risks
      rather than political biases. Although this is an appealing goal, it is
      inherently impossible because rank-ordering of the drugs inevitably requires
      value judgements concerning the different types of harm. Such judgements, even by
      scientists, depend upon subjective personal criteria and not only upon scientific
      facts. Moreover, classification that is meant to guide the legal system in
      controlling dangerous drug use can function only if it is in harmony with the
      values and sentiments of the public. In some respects, politicians may be better
      attuned to public attitudes and wishes, and to what policies the public will
      support, than are scientific experts. The problems inherent in such drug
      classification are illustrated by the examples of cannabis and of salvinorin A.
      They raise the question as to whether the classification process really serves
      any socially beneficial purpose.

PMID- 20148797
TI  - Predicting life-time and regular cannabis use during adolescence; the roles of
      temperament and peer substance use: the TRAILS study.
AB  - AIMS: The aim of the present study was to determine the mediating role of
      affiliation with cannabis-using peers in the pathways from various dimensions of
      temperament to life-time cannabis use, and to determine if these associations
      also contributed to the development of regular cannabis use. METHODS: Objectives
      were studied using data from 1300 participants of the Tracking Adolescents'
      Individual Lives Survey (TRAILS), a large, general population study of Dutch
      adolescents. We used parent-reports on the Early Adolescent Temperament
      Questionnaire to assess the dimensions of high-intensity pleasure, shyness,
      fearfulness, frustration and effortful control at age 10-12 years. By means of
      self-reports, life-time and regular cannabis use were determined at age 15-18
      years, and proportion of substance-using peers was determined at ages 12-15 and
      15-18 years. Models were adjusted for age, sex, intelligence and parental
      cannabis use. RESULTS: High-intensity pleasure [odds ratio (OR) = 1.09, 95%
      confidence interval (CI) = 1.05-1.13] and effortful control (OR = 0.92, 95% CI =
      0.89-0.96) affected the risk for life-time cannabis use through their influence
      on affiliation with cannabis-using peers. Shyness affected this risk
      independently from peer cannabis use. Only the pathway from effortful control was
      associated additionally with the development of regular cannabis use (OR = 0.93,
      95% CI = 0.89-0.98). CONCLUSIONS: Peer cannabis use and, to a lesser extent,
      certain temperamental characteristics affect an adolescent's risk of cannabis
      use, and should be considered in prevention programmes. We recommend future
      research to focus upon factors that potentially modify the association between
      temperament, affiliation with cannabis-using peers and cannabis use.

PMID- 20148800
TI  - Of cats and mites: withdrawal of Xolair after prolonged use.

PMID- 20148798
TI  - Oral tacrolimus (FK 506) in refractory paediatric ulcerative colitis.

PMID- 20148801
TI  - Usefulness of the basophil activation test (BAT) in the diagnosis of life
      threatening drug anaphylaxis.

PMID- 20148802
TI  - Anaphylaxis to Raphanus niger.

PMID- 20148803
TI  - Toothpaste-induced anaphylaxis caused by mint (Mentha) allergy.

PMID- 20148804
TI  - The costs and consequences of omalizumab in uncontrolled asthma from a USA payer
      perspective.
AB  - BACKGROUND: Omalizumab, an anti-immunoglobulin E antibody, reduces exacerbations
      and symptoms in uncontrolled allergic asthma. The study objective was to estimate
      the costs and consequences of omalizumab compared to usual care from a US payer
      perspective. METHODS: We estimated payer costs, quality-adjusted survival
      (QALYs), and the incremental cost-effectiveness ratio (ICER) of omalizumab
      compared to usual care using a state-transition simulation model that included
      sensitivity analyses. Every 2 weeks, patients could transition between chronic
      asthma and exacerbation health states. The best available evidence informed the
      clinical and cost input estimates. Five years of omalizumab treatment followed by
      usual care was assumed to estimate a lifetime horizon. Omalizumab responders
      (60.5% of treated) were modeled as a separate scenario where nonresponders
      reverted back to usual care after 16 weeks of active treatment. RESULTS: The mean
      lifetime discounted costs and QALYs were $83,400 and 13.87 for usual care and
      $174,500 and 14.19 for omalizumab plus usual care resulting in $287 200/QALY (95%
      interval: $219,300, $557, 900). The ICER was $172 300/QALY when comparing
      omalizumab to usual care in the responder scenario. One-way sensitivity analyses
      indicated that the results were sensitive to the difference in treatment-specific
      utilities for the chronic state, exacerbation-associated mortality, omalizumab
      price, exacerbation rates, and response definition. CONCLUSIONS: The results
      suggest that adding omalizumab to usual care improves QALYs at an increase in
      direct medical costs. The cost-effectiveness of omalizumab is similar to other
      chronic disease biologics. The value increases when omalizumab response is used
      to guide long-term treatment.

PMID- 20148805
TI  - Towards a European registry of severe allergic reactions: current status of
      national registries and future needs.
AB  - The incidence of severe allergic reactions is largely unknown and information
      about triggering allergens, aggravating factors, demography of patients and
      medical care is lacking. A European wide registry could provide a powerful tool
      to improve the management of severe allergic reactions from both a medical and a
      public health perspective. Analysis of existing registries regarding the type and
      quality of data being collected was used to develop a plan for a pan-European
      registry, including the type of system to be used and the range of data to be
      entered. Surveillance will provide evidence for the efficacy of risk management
      measures and may identify the emergence of new allergenic foods, and aid
      monitoring of novel foods, ingredients and technologies. Patients need a clear
      indication of factors that may increase their risk of having an adverse reaction,
      which such a registry can help compile. Based on the collected data, food
      businesses will be able to develop educational programmes for allergen risk
      assessment and allergen risk communication. Finally, and most importantly
      preventive measures can be developed and government agencies receive population
      based data which may be relevant for legislative purposes.

PMID- 20148806
TI  - CC chemokine receptor 4 (CCR4) in human allergen-induced late nasal responses.
AB  - BACKGROUND: CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2
      lymphocytes. CCR4-mediated inflammation may be important in the pathology of
      allergic rhinitis. Disruption of CCR4 - ligand interaction may abrogate allergen
      induced inflammation. METHODS: Sixteen allergic rhinitics and six nonatopic
      individuals underwent both allergen and control (diluent) nasal challenges.
      Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were
      taken at 8 h post challenge. Sections were immunostained and examined by light or
      dual immunofluorescence microscopy for eosinophils, T-lymphocytes, CCR4(+)CD3(+)
      and CXCR3(+)CD3(+) cells and examined by in situ hybridization for CCR4, IL-4 and
      IFN-gamma mRNA(+) cells. Peripheral blood mononuclear cells were obtained from
      peripheral blood of nine normal donors and the CCR4(+)CD4(+) cells assessed for
      actin polymerization in response to the CCR4 ligand macrophage-derived chemokine
      (MDC/CCL22) and the influence of a CCR4 antagonist tested. RESULTS: Allergic
      rhinitics had increased early and late phase symptoms after allergen challenge
      compared to diluent; nonatopics did not respond to either challenge. Eosinophils,
      but not total numbers of CD3(+) T cells, were increased in rhinitics following
      allergen challenge. In rhinitics, there was an increase in CCR4(+)CD3(+) protein
      positive cells relative to CXCR3(+)CD3(+) cells; CCR4 mRNA+ cells were increased
      and IL-4 increased to a greater extent than IFN-gamma. CCR4(+)CD4(+) T cells
      responded to MDC in vitro, and this response was inhibited by the selective CCR4
      antagonist. CONCLUSION: Lymphocyte CCR4 expression is closely associated with
      induction of human allergen-induced late nasal responses. Blocking CCR4-ligand
      interaction may provide a novel therapeutic approach in allergic disease.

PMID- 20148807
TI  - The effect of high gravidity on the carcinogenesis of mammary gland in TA2 mice.
AB  - PROBLEM: Spontaneous breast cancer in Tientsin Albinao 2 (TA2) mice, like human
      pregnancy-associated breast cancer (PABC), often occurs in pregnancy and
      puerperium, especially in mice with high gravidity. We hypothesized that the
      dysfunction of cellular immunity caused by the increase of 17beta-estradiol (E2)
      and progesterone (P) might be one of the reasons for carcinogenesis of mammary
      gland. METHOD OF STUDY: We investigated the T lymphocyte subsets and the
      concentration of serum hormone and cytokines in cancer-bearing, pregnant or
      postpartum TA2 mice using flow cytometry, chemiluminescent immunoassay, and
      enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: The number of T
      lymphocytes and the concentration of E2, P, interleukin-2 (IL-2), IL-4, and
      interferon-gamma (IFN-gamma) changed with the increase of pregnancy and
      puerperium. During four pregnancies, elevated E2 and P resulted in a decrease in
      the number of CD3(+), CD4(+) T lymphocytes, CD4(+)/CD8(+) ratio, and the
      concentration of IL-2, IL-4, and IFN-gamma. Data in the fourth pregnancy were the
      closest to those of cancer-bearing mice. CONCLUSION: T lymphocyte subsets and
      concentration of IL-2, IL-4, and IFN-gamma are affected by E2 and P during
      multiple pregnancy and delivery to some degree, which may contribute to the
      genesis of spontaneous breast cancer in TA2 mice.

PMID- 20148808
TI  - Listing for expanded criteria donor kidneys in older adults and those with
      predicted benefit.
AB  - Certain patient groups are predicted to derive significant survival benefit from
      transplantation with expanded criteria donor (ECD) kidneys. An algorithm
      published in 2005 by Merion and colleagues characterizes this group: older
      adults, diabetics and registrants at centers with long waiting times. Our goal
      was to evaluate ECD listing practice patterns in the United States in terms of
      these characteristics. We reviewed 142 907 first-time deceased donor kidney
      registrants reported to United Network for Organ Sharing (UNOS) between 2003 and
      2008. Of registrants predicted to benefit from ECD transplantation according to
      the Merion algorithm ('ECD-benefit'), 49.8% were listed for ECD offers ('ECD
      willing'), with proportions ranging from 0% to 100% by transplant center. In
      contrast, 67.6% of adults over the age of 65 years were ECD-willing, also ranging
      from 0% to 100% by center. In multivariate models, neither diabetes nor center
      waiting time was significantly associated with ECD-willingness in any subgroup.
      From the time of initial registration, irrespective of eventual transplantation,
      ECD-willingness was associated with a significant adjusted survival advantage in
      the ECD-benefit group (HR for death 0.88, p < 0.001) and in older adults (HR
      0.89, p < 0.001), but an increased mortality in non-ECD-benefit registrants (HR
      1.11, p < 0.001). In conclusion, ECD listing practices are widely varied and not
      consistent with published recommendations, a pattern that may disenfranchise
      certain transplant registrants.

PMID- 20148809
TI  - Kidneys for sale: who disapproves, and why?
AB  - The shortage of transplant kidneys has spurred debate about legalizing monetary
      payments to donors to increase the number of available kidneys. However, buying
      and selling organs faces widespread disapproval. We survey a representative
      sample of Americans to assess disapproval for several forms of kidney market, and
      to understand why individuals disapprove by identifying factors that predict
      disapproval, including disapproval of markets for other body parts, dislike of
      increased scope for markets and distrust of markets generally. Our results
      suggest that while the public is potentially receptive to compensating kidney
      donors, among those who oppose it, general disapproval toward certain kinds of
      transactions is at least as important as concern about specific policy details.
      Between 51% and 63% of respondents approve of the various potential kidney
      markets we investigate, and between 42% and 58% want such markets to be legal. A
      total of 38% of respondents disapprove of at least one market. Respondents who
      distrust markets generally are not more disapproving of kidney markets; however
      we find significant correlations between kidney market disapproval and attitudes
      reflecting disapproval toward certain transactions-including both other body
      markets and market encroachment into traditionally nonmarket exchanges, such as
      food preparation.

PMID- 20148811
TI  - Alleviating the burden of small-for-size graft in right liver living donor liver
      transplantation through accumulation of experience.
AB  - The issue of small-for-size graft (SFSG) containing the middle hepatic vein in
      right liver living donor liver transplantation from 1996 to 2008 (n = 320) was
      studied. Characteristics of donors, grafts and recipients were comparable between
      Era I (first 50 cases) and Era II (next 270 cases) except that the median model
      for end-stage liver disease (MELD) score was higher in Era I (29 vs. 24; p =
      0.024). The median graft to standard liver volume ratio (G/SLV) in Era I was
      49.0% (range, 32.8-86.2%), versus 49.3% (range, 28.4-89.4%) in Era II (p =
      0.498). Hospital mortality rate, the study endpoint, dropped from 16.0% (8/50) in
      Era I to 2.2% (6/270) in Era II (p = 0.000). Univariate analysis showed that MELD
      score (p = 0.002), pretransplant hepatorenal syndrome (p = 0.000) and Era I (p =
      0.000) were significant in hospital mortality. Logistic regression analysis
      showed that only Era I (relative risk 9.758; 95% confidence interval, 2.885
      33.002; p = 0.000) was significant. In Era I, G/SLV<40% had a relative risk of
      7.8 (95% confidence interval, 1.225-49.677; p = 0.030). The hospital mortality
      rates for G/SLV<40% were 50% (3/6) and 1.9% (1/52) in Era I and II respectively.
      In conclusion, through accumulation of experience, SFSG became less important as
      a factor in hospital mortality.

PMID- 20148814
TI  - Proinflammatory events and HLA antibodies.

PMID- 20148815
TI  - Elevated incidence of posttransplant erythrocytosis after simultaneous pancreas
      kidney transplantation.
AB  - Posttransplant erythrocytosis (PTE) poses a potential risk of thrombosis in
      kidney transplantation. Clinical observation of our systemically drained
      simultaneous kidney pancreas transplant (S-SPK) patients showed a higher
      incidence of PTE and need for phlebotomies. To evaluate the incidence of PTE we
      analyzed hematocrit (Hct) levels and frequency of phlebotomies in 94 SPK as
      compared to 174 living donor (LD) recipients and 53 type-I diabetic with kidney
      transplant only. For study purposes we defined PTE as Hct >50% or the necessity
      for phlebotomies. Kaplan-Meier plots and Cox proportional hazard models were used
      to examine the association between the transplant type and PTE. We found an
      increased incidence of PTE in SPK compared to LD (p < 0.001). In the multivariate
      model, SPK had a 5-fold risk for the development of PTE (AHR 5.3, 95% CI 1.8,
      15.9). The incidence of therapeutic phlebotomy was 13% among SPK patients and 4%
      in LD kidney recipients; 19 patients altogether. A total of 64 units were
      phlebotomized (48-SPK and 16-LD). Type I diabetic patients with a kidney
      transplant showed a 0% incidence of PTE. We observed a greater incidence of PTE
      and phlebotomies in S-SPK compared to LD with kidney only transplant recipients.

PMID- 20148810
TI  - Treg-therapy allows mixed chimerism and transplantation tolerance without
      cytoreductive conditioning.
AB  - Establishment of mixed chimerism through transplantation of allogeneic donor bone
      marrow (BM) into sufficiently conditioned recipients is an effective experimental
      approach for the induction of transplantation tolerance. Clinical translation,
      however, is impeded by the lack of feasible protocols devoid of cytoreductive
      conditioning (i.e. irradiation and cytotoxic drugs/mAbs). The therapeutic
      application of regulatory T cells (Tregs) prolongs allograft survival in
      experimental models, but appears insufficient to induce robust tolerance on its
      own. We thus investigated whether mixed chimerism and tolerance could be realized
      without the need for cytoreductive treatment by combining Treg therapy with BM
      transplantation (BMT). Polyclonal recipient Tregs were cotransplanted with a
      moderate dose of fully mismatched allogeneic donor BM into recipients conditioned
      solely with short-course costimulation blockade and rapamycin. This combination
      treatment led to long-term multilineage chimerism and donor-specific skin graft
      tolerance. Chimeras also developed humoral and in vitro tolerance. Both
      deletional and nondeletional mechanisms contributed to maintenance of tolerance.
      All tested populations of polyclonal Tregs (FoxP3-transduced Tregs, natural Tregs
      and TGF-beta induced Tregs) were effective in this setting. Thus, Treg therapy
      achieves mixed chimerism and tolerance without cytoreductive recipient treatment,
      thereby eliminating a major toxic element impeding clinical translation of this
      approach.

PMID- 20148816
TI  - Survival and length of stay following blood transfusion in octogenarians
      following cardiac surgery.
AB  - Our aim was to assess if peri-operative blood transfusion is an independent risk
      factor for mortality and morbidity in the elderly. We report the results of a
      cohort study of all patients aged 80 or more on the day of their emergency or
      elective cardiac surgery (n = 874), using routinely collected data from January
      2003 to November 2007. The primary outcome was all-cause mortality in hospital.
      The secondary outcomes were duration of stay in the intensive care unit (ICU) and
      overall hospital stay. Confounding variables were used to build up a risk model
      using a multivariable logistic regression analysis, and blood transfusion was
      added to assess whether it had additional predictive value for hospital
      mortality. Patients were divided into three groups: (i) transfusion of 0-2 units
      of red blood cells; (ii) transfusion of > 2 units of red blood cells and (iii)
      transfusion of red blood cells plus other clotting products. The strongest
      independent predictors of hospital death were logistic EuroSCORE and body mass
      index. After inclusion of these two variables, the odds ratio for transfusion
      remained significant. Relative to 0-2 units, the odds ratio for > 2 units was
      6.80 (95% CI 2.46-18.8), and for other additional blood products was 14.4 (95% CI
      5.34-37.3), with a p value of < 0.001. Duration of stay in the ICU was
      significantly associated with the amount of blood products administered (median
      (IQR [range]) ICU stay 1 (1-2 [0-15]) day if transfused 0-2 units of red blood
      cells, 2 (1-6 [0-128]) days if transfused > 2 units of red blood cells and 3 (1
      76 [0-114]) days if other clotting products were used; p value < 0.001). Hospital
      stay was also associated with the amount of red cells used (p < 0.001).

PMID- 20148820
TI  - Factors affecting the relationship between arterial and end-tidal carbon dioxide
      pressures in the anaesthetised horse.
AB  - OBJECTIVE: To assess the effects of the duration of anaesthesia, position of
      recumbency, mode of ventilation, anaesthetic drug protocol, patient age and type
      of surgical procedure on the usefulness of capnometry as a measure of the partial
      pressure of arterial carbon dioxide (P(a)co(2)) during general anaesthesia in
      horses. DESIGN: A prospective study compared the P(a)co(2) values with those of
      partial pressure of end-tidal carbon dioxide (ETco(2)) in horses anaesthetised
      for elective or emergency surgical procedures. The difference between P(a)co(2)
      and ETco(2) (P(a)co(2)- ETco(2)) and the physiological dead space to tidal volume
      ratio (V(D)/V(T)) were calculated. The effects of the study parameters on these
      variables was determined. RESULTS: The agreement between P(a)co(2) and ETco(2)
      was poor. P(a)co(2)- ETco(2) and V(D)/V(T) during the first 60 min of anaesthesia
      was significantly less than after 60 min of anaesthesia. Mode of ventilation,
      position of recumbency, anaesthetic drug protocol, patient age and type of
      procedure did not have a significant affect on either value. CONCLUSIONS:
      P(a)co(2)- ETco(2) in anaesthetised horses can be large, making ETco(2)
      unreliable as a predictor of P(a)co(2) and for assessment of pulmonary
      ventilation. For anaesthesia lasting less than 60 min at least one blood gas
      analysis of an arterial blood sample is required to assess P(a)co(2)- ETco(2).
      Arterial blood gas analysis should be repeated after 60 min of general
      anaesthesia.

PMID- 20148819
TI  - Retrospective study of 108 foals with septic osteomyelitis.
AB  - OBJECTIVE: To determine the clinical characteristics, short-term outcome and
      future athletic performance of foals with septic osteomyelitis. DESIGN:
      Retrospective clinical study of 108 Thoroughbred foals with radiographic evidence
      of bone infection that were presented at the Scone Veterinary Hospital between
      August 1995 and December 2001. Medical records were reviewed and information
      concerning signalment, the clinical, laboratory and radiographic findings,
      treatment and outcome was obtained. Racing records were obtained and evaluated
      for surviving foals that had reached racing age. RESULTS: Mean age of foals at
      initial evaluation was 39 days (range 1-180 days); 21 foals had multiple
      radiographic bone lesions (19.4%), and 76 had concurrent septic arthritis
      (70.4%). The most frequently affected bones were the femur, tibia and distal
      phalanx. In total, 87 foals were discharged from the hospital (80.6%), 79
      survived long-term to reach racing age and 52 raced (65.8%). Overall, 48%
      (52/108) of the foals treated for osteomyelitis raced. Foals less than 30 days of
      age at the time of diagnosis, critically ill foals and those with multiple bones
      or joints affected were significantly less likely to be discharged from hospital.
      Multiple septic joints, but not multiple bone involvement, had an unfavourable
      prognosis for racing. CONCLUSIONS: The prognosis for survival of foals with
      septic osteomyelitis or osteitis is favourable. Multiple bone or joint
      involvement is an important short-term prognostic indicator; however, the
      involvement of multiple joints, but not multiple infected bones, is associated
      with an unfavourable prognosis for racing.

PMID- 20148821
TI  - Mastocytoma in the common carpal sheath of the digital flexor tendons of a horse.
AB  - A 13-year-old Morgan gelding was examined for right forelimb lameness and
      tenosynovitis of the right common carpal sheath of the digital flexor tendons.
      The horse had moderate right forelimb lameness at the trot and marked effusion of
      the right common carpal sheath of the digital flexor tendons. Ultrasonographic
      examination revealed a soft tissue mass within the proximal pouch of the affected
      tendon sheath, located adjacent to the distal physis of the radius. Cytology and
      culture of the fluid revealed a sterile, eosinophilic tenosynovitis. Tenoscopic
      exploration confirmed the presence of a capsulated soft tissue mass. Thecotomy
      was required to fully debride the mass, which histology revealed to be a mast
      cell tumour. At 22 months postoperatively, the horse developed mild right
      forelimb lameness and eosinophilic tenosynovitis because of recurrence of the
      mastocytoma. Mastocytosis is a possible differential diagnosis in any horse
      exhibiting lameness associated with tenosynovitis. Surgical excision combined
      with rest and postoperative intrasynovial and systemic corticosteroids may be
      palliative.

PMID- 20148823
TI  - Immune-mediated haemolytic anaemia in 110 dogs in Victoria, Australia.
AB  - OBJECTIVE: Evaluate the survival and prognostic indicators (i.e. breed
      predilection, season, blood transfusion, and the prevalence of autoagglutination)
      of dogs with immune-mediated haemolytic anaemia (IMHA) in Victoria, Australia.
      DESIGN: Retrospective study of 110 diagnosed with primary IMHA at the University
      of Melbourne Veterinary Clinic and Hospital. RESULTS: In total, 80 of the dogs
      (72.7%) were discharged from hospital and 48 of 65 (73.8%) dogs available for
      follow-up were known to be alive at 1 year, giving an overall 1-year survival of
      48 (50.5%) of 95 dogs for which survival data were available. Regarding breed, 80
      (18.2%) of the 110 dogs were Maltese-breed dogs compared with 81 (7.4%) of 1100
      control dogs (P < 0.001). Springer Spaniels (P = 0.02), Hungarian Vizslas (P =
      0.02) and Airedale Terriers (P < 0.001) were also over-represented compared with
      the control sample. There was no evidence of an association between the
      occurrence of IMHA in dogs and season in this study. Receiving one or more blood
      transfusions did not affect survival to the time of discharge from hospital. On
      initial blood smear examination, 57 (51.8%) of the 110 dogs had spontaneous
      autoagglutination and its presence was associated with decreased survival to
      discharge from hospital (P = 0.03). Packed cell volume, white cell count,
      platelet count and serum total bilirubin on admission had no effect on survival
      to the time of discharge from hospital or 1 year later. CONCLUSION: Dogs with
      IMHA have a guarded prognosis as only half are still alive 1 year after the acute
      event.

PMID- 20148824
TI  - Serological prevalence study of exposure of cats and dogs in Launceston,
      Tasmania, Australia to spotted fever group rickettsiae.
AB  - A sero-epidemiological study of cats and dogs in the Launceston area of Tasmania,
      Australia was undertaken to determine the prevalence of antibodies to spotted
      fever group (SFG) rickettsiae. Results showed that 59% of cats and 57% of dogs
      were positive for antibodies, but there was no correlation between the animal's
      health and seropositivity at the time of testing, suggesting that rickettsial
      exposure is unrelated to ill-health in these two species of domestic animals.

PMID- 20148825
TI  - Serological analysis of Chlamydophila abortus in Australian sheep and
      implications for the rejection of breeder sheep for export.
AB  - OBJECTIVE: To examine the incidence of positive results in a complement fixation
      test (CFT) and enzyme-linked immunosorbent assay (ELISA) for Chlamydophila
      abortus in Australian sheep and how this incidence differs with state of origin,
      age, sex, breed and property. To examine the consequences in relation to
      rejection of breeder sheep for export. DESIGN: Collection of blood samples from
      891 sheep on 109 properties in southern Australia. All samples had a unique,
      coded property identification. PROCEDURE: The samples were tested using the
      Institut Pourquier Chlamydophila abortus antibody ELISA (rELISA) and a CFT.
      Residual maximum likelihood analyses of the sample to positive ratio of the
      corrected optical density for the rELISA and generalised linear mixed model
      analyses of the CFT outcomes were carried out. RESULTS: The sample to positive
      ratio of the corrected optical density values of the rELISA did not differ
      between sex, age, breed or state of origin, but differed greatly between
      properties. The CFT outcome did not differ between age, breed or state of origin,
      but differed greatly between properties and was more often positive with rams
      than with ewes. CONCLUSION: Positive outcomes to C. abortus antibody tests are
      very common in Australia. Rams have a particularly high incidence of positive
      results with the CFT. Rejection of sheep and property consignments is likely to
      be very common with all tests and situations examined except for the CFT (at 1:32
      dilution) in ewes.

PMID- 20148826
TI  - Femoral diaphysis fractures in cattle: 26 cases (1994-2005).
AB  - OBJECTIVE: This retrospective study was conducted to evaluate the outcome for
      cattle with diaphyseal fractures of the femur, but not including capital physeal
      injuries. METHODS: Sources of information were medical records of cattle having a
      definitive diagnosis of diaphyseal femoral fractures and telephone survey of
      owners. RESULTS: Medical records for 26 cattle with femoral fracture were found;
      of the 20 aged less than 2 months, 15 were treated surgically, 4 conservatively
      (stall rest) and 1 was euthanased without treatment. The surgical treatment
      varied according to the configuration of the fracture and the surgeon's
      experience. Surgery for mid-diaphyseal fractures had a significantly better
      surgical outcome then distal diaphyseal fractures (P < 0.05), as there were
      significantly fewer postoperative complications. Of the 15 calves treated
      surgically, 10 were discharged from hospital and 5 were retained in the herd
      without noticeable lameness. Of the 4 calves treated conservatively, 3 were alive
      at follow-up, but 2 were still lame. Of the 6 older cattle, 3 were euthanased
      without treatment and 3 were treated conservatively, 2 of which were alive at
      follow-up but 1 was still lame. CONCLUSION: Conservative treatment of femur
      fracture in cattle is possible but associated with complications during the
      convalescence. Continued research is needed to optimise distal diaphyseal
      fracture stabilisation in young cattle.

PMID- 20148827
TI  - Haemolytic anaemia in cattle in NSW associated with Theileria infections.
AB  - Several outbreaks of anaemia, jaundice, abortion and mortality in cattle in New
      South Wales were attributed to the intracellular parasite, Theileria buffeli.
      Disease occurred predominantly in periparturient animals that had been moved from
      inland to coastal areas. Diagnosis was made via exclusion of other causes of
      haemolytic anaemia and observation of the parasite in blood smears. Treatments
      included both registered and non-registered products. There is a possibility of a
      new strain of Theileria sp. in Australia and the possible vectors encountered in
      NSW are discussed.

PMID- 20148828
TI  - Using a GnRH agonist to obtain an index of testosterone secretory capacity in the
      cockatiel (Nymphicus hollandicus) and sulphur-crested cockatoo (Cacatua
      galerita).
AB  - OBJECTIVE: Validation of a stimulation test for determining the steroidogenic
      capacity of the parrot testis. The major aim was to characterise testosterone
      secretion after injection of a gonadotropin-releasing hormone agonist (GnRHa),
      then use the test to investigate seasonal reproduction in the male cockatiel.
      PROCEDURE: A synthetic GnRHa (buserelin; 8.0 microg of peptide/kg bodyweight) was
      injected IM into male cockatiels (n = 7) and sulphur-crested cockatoos (n = 3)
      and serial blood samples collected at 0, 30, 60, 90 and 120 min after
      administration. Once validated, the technique was subsequently used to examine
      seasonal changes (23 months) in the testosterone profile of a captive cockatiel
      population. RESULTS: Injection of buserelin resulted in a significant increase in
      the testosterone concentration of cockatiel plasma, with maximal concentrations
      occurring at approximately 60 (1.33 +/- 0.08 ng/mL) to 90 min (1.22 +/- 0.08
      ng/mL) after injection. Although no clear pattern of seasonal variation in
      testosterone secretion was detected in cockatiel plasma, samples taken 60 and 90
      min after administration showed a significant increase in all seasons. Injection
      of buserelin in the sulphur-crested cockatoo also resulted in increased
      testosterone secretion, with maximal concentrations obtained after 90 min.
      CONCLUSION: Buserelin can be used to obtain a reliable index of the prevailing
      testosterone capacity of the cockatiel and cockatoo testis. With further studies,
      this test may be incorporated into clinical assessment of reproductive status.

PMID- 20148829
TI  - Seminoma in a southern black rhinoceros (Diceros bicornis minor): diagnosis,
      surgical management and effect on fertility.
AB  - A testicular mass was identified by ultrasonography performed during a routine
      reproductive evaluation of an adult male southern black rhinoceros (Diceros
      bicornis minor). Histological examination of a testicular biopsy supported a
      presumptive diagnosis of testicular neoplasia. Hemi-castration was performed to
      excise the affected testis and a pathological diagnosis of a seminoma was made.
      Assessment of semen suggested reduced fertility as a consequence of the
      neoplastic process, but hemi-castration prevented further growth and metastasis
      of the tumour and ensured the animal's breeding potential. This is the second
      documented case of a seminoma in a rhinoceros species and the first case in a
      black rhinoceros.

PMID- 20148830
TI  - Many faces of graft-versus-host disease.
AB  - Allogeneic haematopoietic stem cell transplantation is increasingly used in the
      treatment of malignant and non-malignant disorders. Despite ongoing advances in
      the field, morbidity and mortality related to graft-versus-host disease remains a
      major barrier to its application. Graft-versus-host disease is a difficult-to
      diagnose disease. Dermatologists are involved due to its diverse cutaneous
      expression. In order to appropriately diagnose, classify and treat this complex
      disease, knowledge of its expanding cutaneous expression is required. This review
      provides a synopsis of the clinical manifestations of acute, lichenoid and
      sclerodermatous phases of graft-versus-host disease with a look at the current
      evidence surrounding its differential diagnosis.

PMID- 20148833
TI  - Short-term morbidity associated with sentinel lymph node biopsy in cutaneous
      malignant melanoma.
AB  - Guidelines for the surgical treatment of cutaneous primary malignant melanoma are
      well established; however, the approach to the treatment of the regional lymph
      nodes remains more controversial. In many centres, sentinel lymph node biopsy has
      been adopted as routine in the treatment of malignant melanoma for prognostic
      purposes, as it is not of proven therapeutic benefit. The Multicentre Selective
      Lymphadenectomy Trial II aims to determine the comparative benefits of subsequent
      completion lymphadenectomy versus observation in those found to have a positive
      sentinel node biopsy. Until results are available, the risks of the procedure
      must be weighed against the value of prognostic information gained from
      performing a sentinel node biopsy. In this retrospective analysis of sentinel
      lymph node biopsies at our institution, we show that in general, short-term
      morbidity associated with this procedure is low, but that morbidity is higher in
      a subgroup of people with higher weight or body mass index, and in those whose
      biopsy is located in the groin.

PMID- 20148834
TI  - Editorial: sentinel lymph node biopsy.

PMID- 20148835
TI  - True blue football fan: tattoo reaction confined to blue pigment.
AB  - A tattoo reaction which appeared solely on the blue pigment of a 6-month old red
      and blue football club tattoo of an ardent fan was investigated. The patient was
      otherwise asymptomatic and no other abnormality was detected on full physical
      examination. Histology revealed a florid sarcoidal granuloma reaction to blue
      pigment. Preliminary investigations for systemic sarcoidosis did not reveal any
      abnormality. The tattoo reaction flattened clinically with the institution of a
      short course of topical mometasone furoate 0.1% ointment and as the subject
      remained asymptomatic, close surveillance for the development of systemic
      sarcoidosis is to continue. The possibility of delayed type hypersensitivity is
      discussed.

PMID- 20148836
TI  - Nickel allergy presenting as mobile phone contact dermatitis.
AB  - A 39-year-old man presented with a 6-month history of a treatment-resistant
      facial dermatitis. The patient regularly used his mobile phone, predominantly on
      the left cheek. Patch testing confirmed the clinical suspicion of mobile phone
      contact dermatitis from nickel contained in the phone casing. Although
      infrequently reported, with the trend towards metallic mobile phone casings and
      the high incidence of nickel sensitization in the community, the incidence of
      mobile phone contact dermatitis is likely to increase.

PMID- 20148837
TI  - Primary cutaneous carcinosarcoma: dermoscopic and immunohistochemical features.
AB  - A 73-year-old man presented a 9-month history of an enlarging nodule on his right
      temple. Dermoscopy revealed a non-pigmented lesion with ulceration, fibrosis and
      pale globules. An excisional biopsy was carried out and histology showed a
      biphasic tumour with a basal cell carcinoma like epithelial component and a
      dermal undifferentiated sarcoma, with pleomorphic spindle cells and numerous
      osteoclast-like giant cells. Based on immunohistochemistry findings, a diagnosis
      of primary cutaneous carcinosarcoma was made and the patient underwent wide local
      excision.

PMID- 20148838
TI  - A dramatic response to a single dose of infliximab as rescue therapy in acute
      generalized pustular psoriasis of von Zumbusch associated with a neutrophilic
      cholangitis.
AB  - Generalized pustular psoriasis of von Zumbusch is an unstable, inflammatory form
      of psoriasis, with the hallmark of neutrophil infiltration in cutaneous as well
      as extracutaneous lesions. It is often recalcitrant, making treatment difficult.
      Tumour necrosis factor-alpha antagonists including infliximab have been used with
      success in treating recalcitrant cases. We report a case of a 48-year-old Chinese
      female patient with a long-standing history of poorly controlled generalized
      pustular psoriasis which was resistant to multiple therapies. During a severe
      flare, a single dose of infliximab resulted in rapid clearing of cutaneous
      lesions, together with resolution of liver function abnormalities that are likely
      secondary to neutrophilic cholangitis. Subsequent maintenance therapy with
      acitretin allowed remission of pustular disease for 7 months. This demonstrates
      the efficacy of single-dose infliximab for both cutaneous lesions and systemic
      hepatic involvement in generalized pustular psoriasis.

PMID- 20148839
TI  - Clinical improvement in Darier's disease with photodynamic therapy.
AB  - We report a patient with Darier's disease successfully treated with photodynamic
      therapy. She had previously been recalcitrant to treatment with emollients,
      topical corticosteroids and retinoids. Photodynamic therapy was trialled with
      significant clinical improvement in her cutaneous symptoms and signs that was
      maintained for over 27 months.

PMID- 20148840
TI  - A case of multiple angiomas without any angiokeratomas in a female heterozygote
      with Fabry disease.
AB  - Fabry disease is a rare, X-chromosome-linked lysosomal storage disease caused by
      a deficient alpha-galactosidase A enzyme. The disease manifests primarily in
      affected hemizygous males and to some extent in heterozygous females ('carrier').
      A 45-year-old female Fabry disease patient without angiokeratomas but with
      numerous angiomas is presented. Her leukocyte alpha-galactosidase A activity was
      reduced (0.35 nmol/min/mg protein; normal range: 0.4-1). The analysis of her
      alpha-galactosidase A gene (exon 1-7) showed the transition c.427 G>A. An
      intrafamilial follow-up search detected a reduced leukocyte alpha-galactosidase A
      activity in her father, who suffered exclusively from coronary heart disease. Our
      case report underlines the possible wide range of clinical signs in Fabry disease
      patients, sometimes complicated by missing typical lesions (e.g. angiokeratomas).
      In oligosymptomatic Fabry disease cases, genetic analysis is recommended.

PMID- 20148841
TI  - Simultaneous scrofuloderma and intracranial tuberculomas: a rare presentation of
      systemic tuberculosis.
AB  - Tuberculosis can involve multiple organ systems concurrently. We report a case of
      simultaneous brain tuberculomas and scrofuloderma occurring in the same patient.
      Skin biopsies confirmed scrofuloderma and the patient was successfully treated
      for tuberculosis with resolution of the brain masses. This case illustrates the
      importance of dermatological manifestations of systemic disease as an accessible
      source for diagnosis and guidance in appropriate therapy.

PMID- 20148842
TI  - Cutaneous heterotopic bronchogenic tissue in the scapular area.
AB  - Cutaneous bronchogenic anomalies are very rare lesions, and most of them present
      as cysts and/or sinus tracts in the subcutaneous layer. We report a 15-year-old
      boy who presented with a crusted and papillomatous plaque over the right scapular
      region. Histopathological examination of this plaque revealed pseudostratified
      ciliated columnar epithelium with papillary invaginations that included mucinous
      material. The lesion had no cyst or sinus formation and was bordered with smooth
      muscle bundles in stroma.

PMID- 20148843
TI  - Sporotrichoid Mycobacterium marinum infection of the face following a cat
      scratch.
AB  - Mycobacterium marinum infections in humans uncommonly affect the face and are not
      known to be associated with cat scratches. We describe a 24-year-old woman who
      presented with a 3-month history of multiple tender, occasionally discharging
      cystic nodules involving the left side of her face in a sporotrichoid
      distribution. She had suffered a cat scratch to her left lower eyelid 3 weeks
      before the onset of the eruption and owned multiple tropical fish tanks. She was
      systemically well and had no lymphadenopathy. She had a background history of a
      4.5-mm-thick nodular melanoma of her temple treated by wide local excision and
      negative sentinel lymph node biopsy 4 years prior. Skin biopsies showed multiple
      variably sized granulomas surrounded by thick cuffs of lymphocytes involving the
      superficial and deep dermis with no organisms seen on Ziehl-Neelsen, peroidic
      acid-Schiff and methenamine silver stains. Laboratory investigations showed a
      mildly raised erythrocyte sedimentation rate but normal full blood count and C
      reactive protein. Fluid from the left cheek grew an acid-fast bacillus identified
      as Mycobacterium marinum. The skin eruption cleared after 5-month treatment with
      oral clarithromycin 500 mg twice daily and rifampicin 600 mg daily.

PMID- 20148844
TI  - Hyaluronidase allergy: a rare cause of periorbital inflammation.
AB  - Hyaluronidase is a bovine or ovine testicular protein that is used as an adjunct
      to co-administered medicaments and fluids to enhance their dispersion and
      absorption through the degradation of hyaluronan. While it is a known potential
      allergen, there are few reports of hyaluronidase hypersensitivity. A 56-year-old
      lady presented 8 hours post glaucoma surgery with ipsilateral lacriminorrhoea,
      periorbital erythema, oedema, proptosis, pruritus and conjunctival chemosis.
      Right ocular motility was restricted and visual acuity was reduced. The reaction
      settled with oral corticosteroids and antihistamines. Hyaluronidase allergy was
      confirmed on skin prick testing. Hyaluronidase allergy is rare. In the few cases
      reported, reactions occurred at various doses and were acute (intraoperative),
      early (within hours), intermediate (within days) or delayed (within weeks).
      Anaphylaxis has also been described. Primary sensitization appears to be a
      prerequisite for most reactions. The variability in onset of symptoms and the
      response to skin testing would suggest that type I and type IV hypersensitivity
      may both contribute to this response. In this case, the timing fitted with a late
      phase type 1 reaction. This case shows that despite being less common than
      haemorrhage for acute reactions and infection for delayed reactions, allergy can
      account for orbital inflammation following ophthalmic surgery.

PMID- 20148845
TI  - Amoebiasis cutis: clinical suspicion is the key to early diagnosis.
AB  - Amoebiasis cutis is a rare manifestation of Entamoeba histolytica, primarily an
      intestinal pathogen, which occurs as a complication of amoebic dysentery. Primary
      cutaneous amoebiasis occurs from contamination of pre-existing wounds. A high
      degree of clinical suspicion and demonstration of trophozoites from lesions are
      important for making an early diagnosis lest these patients should suffer
      significant morbidity. A HIV-negative and otherwise healthy 40-year-old man
      presented with a well-defined, indurated, painful, progressively enlarging plaque
      with overlying ulcers and pus discharging sinuses involving buttocks,
      perianal/perineal area and part of the left thigh of 3 years' duration. A wide
      array of investigations was unhelpful but demonstration of Entamoeba histolytica
      trophozoites in wet-drop preparation from the ulcer margin was diagnostic. The
      trophozoites were also visualized both in H&E and periodic acid Schiff-stained
      histological sections. Resolution of lesion was observed 2 weeks after treatment
      with oral metronidazole 800 mg three times a day and wound care.

PMID- 20148846
TI  - Peripheral nerve field stimulation for pruritus relief in a patient with notalgia
      paraesthetica.
AB  - This case study is presented to exemplify the application of peripheral nerve
      field stimulation in the treatment of recalcitrant notalgia paraesthetica. The
      patient was a 60-year-old woman with severe and disabling notalgia paraesthetica.
      The itch persisted despite the use of several medications - topical and oral.
      Following a successful trial of peripheral nerve field stimulation with a
      temporary electrode, two subcutaneous electrodes were inserted into the affected
      area with a battery implanted subcutaneously in her right buttock. The patient
      was reviewed at 5 months post implantation. She reported a greater than 85%
      improvement in her itch. She also reported a major improvement in her quality of
      life, with particular improvement in her ability to sleep through the night. This
      case illustrates the possible utilization of peripheral nerve field stimulation
      in the treatment of notalgia paraesthetica, which is a common yet poorly
      understood and treated condition. Replication and controlled studies are required
      to determine the general applicability of this approach.

PMID- 20148847
TI  - Isolated symptomatic cutaneous disease in hypereosinophilic syndrome.
AB  - A 41-year-old Phillipino man presented with a 3-year history of a relapsing and
      remitting generalized chronic pruritic erythematous papular and plaque-like
      eruption. Investigations showed a persistently elevated eosinophil count. His
      disease was limited to cutaneous involvement with an absence of demonstrable
      internal organ involvement, despite extensive investigations and
      multidisciplinary review. Other causes of eosinophilia were excluded. A diagnosis
      of idiopathic hypereosinophilic syndrome was made. Our patient's presentation
      raises a number of issues related to hypereosinophilic syndrome. In particular,
      relating to managing hypereosinophilic syndrome and the challenge of minimizing
      therapy side-effects. Our case highlights the considerable morbidity of untreated
      isolated cutaneous disease, for which he was hospitalized with suicidal
      ideations. In a minority of reports, skin involvement is the only manifestation
      of hypereosinophilic syndrome.

PMID- 20148848
TI  - Acute unilateral poliosis concurrent with trigeminal autonomic cephalalgia: a
      possible aetiological association.
AB  - We report a 24-year-old man who presented with the sudden onset of unilateral
      poliosis associated with acute trigeminal autonomic cephalalgia, suggesting a
      pathophysiology in common and a possible neural hypothesis in the development of
      segmental vitiligo. Although rare, associations with neurological abnormalities
      should be considered in cases of focal depigmentation disorders.

PMID- 20148850
TI  - A dermoscopic case of 'naevus of special sites'.

PMID- 20148851
TI  - Hyaluronic acid filler injections with a 31-gauge insulin syringe.
AB  - Hyaluronic acid gel is a commonly used skin/soft tissue filler in cosmetic
      dermatology. Hyaluronic acid fillers are packaged in proprietary luer-lock
      syringes that can be injected via a 30-gauge, 27-gauge or larger diameter needle
      depending on the consistency of the gel. A method of decanting proprietary
      hyaluronic acid fillers into multiple 31-gauge insulin syringes for injection is
      described. The use of a 31-gauge insulin syringe for filler injections can
      potentially enhance the injection process through more accurate product delivery
      and placement. This has the potential to produce a more balanced and symmetrical
      outcome for patients. Additional benefits include less injection pain, less
      bleeding/bruising and higher levels of patient satisfaction.

PMID- 20148852
TI  - The potpourri approach to hyaluronic acid filler injections.
AB  - There is an ever-expanding range of hyaluronic acid fillers with varying physical
      characteristics available to cosmetic dermatologists. These fillers are
      commercially packaged in syringes of approximately 1 mL (range 0.5-2 mL) volume.
      Filler injectors are currently qualitatively and quantitatively restricted to
      fillers packaged in ready-to-go syringes. Patients often present for pan-facial
      rejuvenation requiring varying amounts of fillers as well as more than one
      type/subtype of filler for optimum correction. The potpourri approach allows
      access to a range of prepared hyaluronic acid filler subtypes that can be used on
      the same patient in the one session. The potpourri method centres on the use of
      multiple 31-gauge insulin syringes prepared with a range of different hyaluronic
      acid filler products that are ready for use. This increases flexibility with
      filler selection and has the potential to provide better filler-to-tissue match
      for patients.

PMID- 20148857
TI  - Asperfuranone from Aspergillus nidulans inhibits proliferation of human non-small
      cell lung cancer A549 cells via blocking cell cycle progression and inducing
      apoptosis.
AB  - Asperfuranone, a novel compound of genomic mining in Aspergillus nidulans, was
      investigated for its anti-proliferative activity in human non-small cell lung
      cancer A549 cells. To identity the anti-cancer mechanism of asperfuranone, we
      assayed its effect on apoptosis, cell cycle distribution, and levels of p53, p21
      Waf1/Cip1, Fas/APO-1 receptor and Fas ligand. Enzyme-linked immunosorbent assay
      showed that the G0/G1 phase arrest might be due to p53-dependent induction of p21
      Waf1/Cip1. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound
      Fas ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the
      apoptotic effect induced by asperfuranone. Our study reports here for the first
      time that the induction of p53 and the activity of Fas/Fas ligand apoptotic
      system may participate in the anti-proliferative activity of asperfuranone in
      A549 cells.

PMID- 20148858
TI  - Duplexed on-microbead binding assay for competitive inhibitor of epidermal growth
      factor receptor by quantitative flow cytometry.
AB  - Upon binding agonist, the epidermal growth factor receptor (EGFR) is dimerized
      and auto-phosphorylated to activate downstream pathway that induces diverse
      physiology and pathology processes. Conventional methods for evaluation of EGFR
      inhibitors are limited. This study describes a duplexed on-microbead binding
      assay allowing competitive EGFR inhibitors to be quantificationally evaluated in
      vitro. Polystyrene microbeads barcoded by fluoresceine isothiocyanate
      fluorescence as high brightness and low brightness microspheres were coated with
      receptor tyrosine kinase (RTK) ligand-epidermal growth factor (EGF)/stem cell
      factor (SCF) and ATP/GTP, respectively. High and low brightness microbeads were
      mixed and incubated with EGFR and its competitive inhibitor in binding assay
      buffer. Phycoerythrin (PE) fluorescence-labelled antibody was employed to report
      the level of EGFR binding to EGF/SCF and ATP/GTP. Values were numbered via PE
      molecules assessed by quantitative flow cytometry. Results from this study
      demonstrated that incubation with EGFR identified by PE-labelled antibody can
      make EGF- and ATP-coated microbeads luminous. And EGF or ATP-competitive EGFR
      inhibitors, respectively, alleviated this in a concentration-dependent manner.
      Coating microbeads with SCF or GTP as a negative control cannot capture EGFR. The
      duplexed on-microbead binding assay in this study might be useful for discovering
      ligand- and ATP-competitive EGFR inhibitors in a rapid and quantificational
      approach.

PMID- 20148859
TI  - Sleep loss induces differential response related to genotoxicity in multiple
      organs of three different mice strains.
AB  - The purpose of the present study was to determine the genetic damage induced by
      paradoxical sleep deprivation (PSD) in three different male mice strains in
      peripheral blood, heart, kidney and liver tissues by the single cell gel (comet)
      assay. Swiss, C57BL/6j and hairless (HRS/j) mice were submitted to PSD by the
      multiple platform technique for 72 hr, and DNA damage was evaluated.
      Statistically significant differences in DNA damage were found in blood cells of
      the Swiss mice strain when compared to negative controls. By contrast, no
      statistically significant differences were found in the C57BL/6j or hairless mice
      strains. With regard to the liver, extensive genotoxic effects were found in the
      Swiss strain. The hairless and C57BL/6j mice strains did not show any signs of
      genotoxocity in this organ. The same lack of effect was noted in kidney and heart
      cells of all strains evaluated. In conclusion, our results reveal that sleep
      deprivation exerted genetic damage in the form of DNA breakage in blood and liver
      cells of the Swiss mice strain only. This type of approach should be considered
      when studying noxious activities on genetic apparatus induced by sleep
      deprivation in mice since the Swiss strain is more suitable for this purpose.

PMID- 20148860
TI  - Functional characterization of CYP2C8.13 and CYP2C8.14: catalytic activities
      toward paclitaxel.
AB  - Cytochrome P450 2C8 (CYP2C8) plays important roles in the metabolism of various
      drugs, including the anti-cancer drug, paclitaxel. We recently identified two
      novel CYP2C8 alleles (CYP2C8*13 and CYP2C8*14; wild-type, CYP2C8*1A) with non
      synonymous single nucleotide polymorphisms in a Japanese population. To precisely
      investigate the effect of amino acid substitutions (CYP2C8*13, Ile223Met;
      CYP2C8*14, Ala238Pro) on CYP2C8 function, CYP2C8 proteins of the wild-type
      (CYP2C8.1) and variants (CYP2C8.13 and CYP2C8.14) were heterologously expressed
      in yeast cells, and their paclitaxel 6alpha-hydroxylation activities were
      determined. The K(m), V(max) and CL(int) values for paclitaxel 6alpha
      hydroxylation of CYP2C8.1 were 2.3 microM, 4.1 pmol/min./pmol CYP and 1.7
      microl/min./pmol CYP, respectively. The K(m) value of CYP2C8.14 was significantly
      higher (2.9-fold) than that of CYP2C8.1. The V(max) value of CYP2C8.14 was
      comparable to that of CYP2C8.1 and the CL(int) value was reduced to 46% of
      CYP2C8.1. In contrast, the K(m), V(max) and CL(int) values of CYP2C8.13 were
      similar to those of CYP2C8.1. These results suggest that Ala238Pro substitution
      in CYP2C8.14 decreases the affinity toward paclitaxel of the CYP2C8 enzyme, and
      that the genetic polymorphism of the CYP2C8*14 allele may influence the clinical
      response to drugs metabolized mainly by CYP2C8.

PMID- 20148861
TI  - Effects of sample size and intraspecific variation in phylogenetic comparative
      studies: a meta-analytic review.
AB  - Comparative analyses aim to explain interspecific variation in phenotype among
      taxa. In this context, phylogenetic approaches are generally applied to control
      for similarity due to common descent, because such phylogenetic relationships can
      produce spurious similarity in phenotypes (known as phylogenetic inertia or
      bias). On the other hand, these analyses largely ignore potential biases due to
      within-species variation. Phylogenetic comparative studies inherently assume that
      species-specific means from intraspecific samples of modest sample size are
      biologically meaningful. However, within-species variation is often significant,
      because measurement errors, within- and between-individual variation, seasonal
      fluctuations, and differences among populations can all reduce the repeatability
      of a trait. Although simulations revealed that low repeatability can increase the
      type I error in a phylogenetic study, researchers only exercise great care in
      accounting for similarity in phenotype due to common phylogenetic descent, while
      problems posed by intraspecific variation are usually neglected. A meta-analysis
      of 194 comparative analyses all adjusting for similarity due to common
      phylogenetic descent revealed that only a few studies reported intraspecific
      repeatabilities, and hardly any considered or partially dealt with errors arising
      from intraspecific variation. This is intriguing, because the meta-analytic data
      suggest that the effect of heterogeneous sampling can be as important as
      phylogenetic bias, and thus they should be equally controlled in comparative
      studies. We provide recommendations about how to handle such effects of
      heterogeneous sampling.

PMID- 20148862
TI  - Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis
      of the evidence.
AB  - OBJECTIVE: The prevalence of suicide attempts (SA) in bipolar II disorder (BPII),
      particularly in comparison to the prevalence in bipolar I disorder (BPI), is an
      understudied and controversial issue with mixed results. To date, there has been
      no comprehensive review of the published prevalence data for attempted suicide in
      BPII. METHODS: We conducted a literature review and meta-analysis of published
      reports that specified the proportion of individuals with BPII in their
      presentation of SA data. Systematic searching yielded 24 reports providing rates
      of SA in BPII and 21 reports including rates of SA in both BPI and BPII. We
      estimated the prevalence of SA in BPII by combining data across reports of
      similar designs. To compare rates of SA in BPII and BPI, we calculated a pooled
      odds ratio (OR) and 95% confidence interval (CI) with random-effect meta-analytic
      techniques with retrospective data from 15 reports that detailed rates of SA in
      both BPI and BPII. RESULTS: Among the 24 reports with any BPII data, 32.4%
      (356/1099) of individuals retrospectively reported a lifetime history of SA,
      19.8% (93/469) prospectively reported attempted suicide, and 20.5% (55/268) of
      index attempters were diagnosed with BPII. In 15 retrospective studies suitable
      for meta-analysis, the prevalence of attempted suicide in BPII and BPI was not
      significantly different: 32.4% and 36.3%, respectively (OR = 1.21, 95% CI: 0.98
      1.48, p = 0.07). CONCLUSION: The contribution of BPII to suicidal behavior is
      considerable. Our findings suggest that there is no significant effect of bipolar
      subtype on rate of SA. Our findings are particularly alarming in concert with
      other evidence, including (i) the well-documented predictive role of SA for
      completed suicide and (ii) the evidence suggesting that individuals with BPII use
      significantly more violent and lethal methods than do individuals with BPI. To
      reduce suicide-related morbidity and mortality, routine clinical care for BPII
      must include ongoing risk assessment and interventions targeted at risk factors.

PMID- 20148863
TI  - Occupational status and social adjustment six months after hospitalization early
      in the course of bipolar disorder: a prospective study.
AB  - OBJECTIVES: Bipolar disorder is often accompanied by poor functional outcomes,
      the determinants of which are not fully understood. We assessed patients with
      bipolar disorder undergoing a hospital admission early in the illness course and
      identified predictors of occupational status, overall social adjustment, and work
      adjustment six months later. METHODS: This was a prospective longitudinal cohort
      study. During hospitalization patients were evaluated with a cognitive battery;
      symptoms, occupational history, and other clinical factors were also assessed. At
      six-month follow-up, patients' symptom remission status was assessed; they were
      also evaluated as to their occupational status, overall social adjustment, and
      work adjustment. Multivariate analyses were used to identify predictors of these
      outcomes. RESULTS: Among the 52 participants, the average rating of overall
      social adjustment at follow-up was between mild and moderate maladjustment. While
      51 had a history of working full time, only 28 (54%) worked full time at follow
      up. A total of 24 (46%) had symptoms that met criteria for a full depression or
      mania syndrome. In multivariate analyses, full-time occupational status at follow
      up was predicted by the absence of baseline substance abuse. Better overall
      social adjustment was predicted by better performance on cognitive tasks of
      processing speed and by symptom remission; the latter variable also predicted
      work adjustment. CONCLUSIONS: Persons with bipolar disorder have limited
      occupational recovery and overall social adjustment six months after a hospital
      admission early in the illness course. Predictors vary among outcomes;
      performance on tasks of processing speed and the extent of symptom remission are
      independently associated with functional outcomes.

PMID- 20148865
TI  - Development and psychometric evaluation of the Bipolar Functional Status
      Questionnaire (BFSQ).
AB  - OBJECTIVES: Persistently impaired psychosocial functioning has been recognized in
      many individuals with bipolar disorder. However, existing measures of functional
      disability have been adapted for use in bipolar disorder based mainly on those
      developed for use in other conditions. The present study involved the development
      and validation of a new patient self-report measure specific to bipolar disorder,
      the Bipolar Functional Status Questionnaire (BFSQ). METHODS: Relevant constructs
      were identified, evaluated, and refined through an expert advisory panel in
      conjunction with patient interviews. Questionnaire items were vetted through
      iterative patient interviews. Psychometric properties were determined based on
      patient responses from implementation of the proposed 33-item questionnaire in an
      11-site study of 596 patients with bipolar disorder across varied phases of
      illness. RESULTS: Eight constructs were identified as fundamental to functional
      status in bipolar disorder: cognitive function, sleep, role functioning,
      emotional functioning, energy/vitality, social functioning, personal management,
      and sexual functioning. Psychometric validation supported item reduction to a 24
      item unidimensional scale, with high internal consistency (coefficient alpha's =
      0.93-0.95), high test-retest reliability (intraclass correlation coefficient =
      0.86, 95% confidence interval = 0.82-0.89), strong convergent validity with other
      functional disability measures (r's > 0.70), and highly significant discriminant
      validity across illness phases, with large effect sizes (Cohen's d > 0.70).
      CONCLUSIONS: The BFSQ is a psychometrically sound self-report measure that can be
      used to effectively quantify functional status across different clinical states
      in patients with bipolar disorder.

PMID- 20148864
TI  - Ten-year diagnostic consistency of bipolar disorder in a first-admission sample.
AB  - OBJECTIVES: A number of reports have examined the stability of the diagnosis of
      schizophrenia, but fewer studies have considered the long-term consistency of a
      bipolar diagnosis or factors that influence the likelihood of a diagnostic
      change. The present study sought to estimate how consistently a bipolar diagnosis
      was made across a 10-year period and factors associated with consistency,
      particularly demographic and clinical characteristics, childhood-related factors,
      and illness course. METHODS: The sample included 195 first-admission patients
      presenting with psychosis who were assessed soon after hospitalization and at 6
      month, 2-year, and 10-year follow-up and diagnosed with bipolar disorder on at
      least one of these assessments. Diagnoses were made using best-estimate
      procedures and were blind to all previous consensus diagnoses. Respondents who
      were consistently diagnosed with bipolar disorder were compared to those whose
      diagnosis shifted across assessments. RESULTS: Overall, 50.3% (n = 98) of the 195
      respondents were diagnosed with bipolar disorder at every available assessment,
      but 49.7% (n = 97) had a diagnostic shift to a non-bipolar disorder at least once
      over the course of the 10-year study. Childhood psychopathology and poorer
      illness course were among the few variables associated with increased odds of a
      change in diagnosis. CONCLUSIONS: Even with optimal assessment practices,
      misdiagnosis of bipolar disorder is common, with complex clinical presentations
      often making it difficult to consistently diagnose the disorder over the long
      term.

PMID- 20148866
TI  - Relationship of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to
      multiple indicators of functioning in people with schizophrenia and bipolar
      disorder.
AB  - OBJECTIVE: This study assessed the relationship between multiple indicators of
      'real-world' functioning and scores on a brief performance-based measure of
      functional capacity known as the Brief University of California San Diego (UCSD)
      Performance-based Skills Assessment (UPSA-B) in a sample of 205 patients with
      either serious bipolar disorder (n = 89) or schizophrenia (n = 116). METHODS:
      Participants were administered the UPSA-B and assessed on the following
      functional domains: (i) independent living status (e.g., residing independently
      as head of household, living in residential care facility); (ii) informant
      reports of functioning (e.g., work skills, daily living skills); (iii)
      educational attainment and estimated premorbid IQ as measured by years of
      education and Wide Range Achievement Test reading scores, respectively; and (iv)
      employment. RESULTS: Better scores on the UPSA-B were associated with greater
      residential independence after controlling for age, diagnosis, and symptoms of
      psychopathology. Among both bipolar disorder and schizophrenia patients, higher
      UPSA-B scores were significantly related to better informant reports of
      functioning in daily living skills and work skills domains. Greater estimated
      premorbid IQ was associated with higher scores on the UPSA-B for both
      schizophrenia and bipolar disorder participants. Participants who were employed
      scored higher on the UPSA-B when controlling for age and diagnosis, but not when
      controlling for symptoms of psychopathology. CONCLUSIONS: These data suggest the
      UPSA-B may be useful for assessing capacity for functioning in a number of
      domains in both people diagnosed with schizophrenia and bipolar disorder.

PMID- 20148868
TI  - The relationship between religious involvement and clinical status of patients
      with bipolar disorder.
AB  - OBJECTIVE: Religion and spirituality are important coping strategies in
      depression but have been rarely studied within the context of bipolar disorder.
      The present study assessed the association between different forms of religious
      involvement and the clinical status of individuals treated for bipolar disorder.
      METHODS: A cross-sectional observation study of follow-up data from a large
      cohort study of patients receiving care for bipolar disorder (n = 334) at an
      urban Veterans Affairs mental health clinic was conducted. Bivariate and
      multivariate analyses were performed to assess the association between public
      (frequency of church attendance), private (frequency of prayer/meditation), as
      well as subjective forms (influence of beliefs on life) of religious involvement
      and mixed, manic, depressed, and euthymic states when demographic, anxiety,
      alcohol abuse, and health indicators were controlled. RESULTS: Multivariate
      analyses found significant associations between higher rates of prayer/meditation
      and participants in a mixed state [odds ratio (OR) = 1.29; 95% confidence
      interval (CI) = 1.10-1.52, chi square = 9.42, df = 14, p < 0.05], as well as
      lower rates of prayer/meditation and participants who were euthymic (OR = 0.84;
      95% CI = 0.72-0.99, chi square = 4.60, df = 14, p < 0.05). Depression and mania
      were not associated with religious involvement. CONCLUSIONS: Compared to patients
      with bipolar disorder in depressed, manic, or euthymic states, patients in mixed
      states have more active private religious lives. Providers should assess the
      religious activities of individuals with bipolar disorder in mixed states and how
      they may complement/deter ongoing treatment. Future longitudinal studies linking
      bipolar states, religious activities, and treatment-seeking behaviors are needed.

PMID- 20148869
TI  - High cortisol levels in the offspring of parents with bipolar disorder during two
      weeks of daily sampling.
AB  - OBJECTIVES: The hypothalamic-pituitary-adrenal (HPA) axis is compromised in major
      depression, bipolar disorder (BD), and in the offspring of parents with major
      depression. Less is known about the offspring of parents with BD (FH+). The
      present project provides follow-up to a previous study showing that the
      adolescent (mean age 16.7 years) FH+ offspring had higher salivary cortisol
      levels than the offspring of parents with no mental disorder (FH-) throughout the
      day in their natural environment, and that girls had higher cortisol levels than
      boys (Ellenbogen MA, Hodgins S, Walker C-D, Adam S, Couture S. Daytime cortisol
      and stress reactivity in the offspring of parents with bipolar disorder.
      Psychoneuroendocrinology 2006; 31: 1164-1180). The goal of the present study was
      to determine whether FH+ offspring, approximately two years later, continued to
      exhibit elevated cortisol levels relative to FH- offspring during two weeks of
      daily sampling. METHODS: The present study examined salivary cortisol levels in
      24 (18.3 +/- 2.6 years) FH+ and 22 (18.0 +/- 2.3 years) FH- offspring who are
      part of the same longitudinal cohort as the previous study. Saliva was collected
      at 1300 h and 1500 h in the natural environment of the offspring during 14
      consecutive days. RESULTS: Multilevel modelling analyses indicated that FH+
      offspring had higher afternoon levels of cortisol in their natural environment
      than FH- offspring, but group differences in slope and gender differences were
      not found. CONCLUSIONS: The FH+ offspring exhibited increased daytime secretion
      of cortisol that, at the level of the group, persisted into late adolescence and
      young adulthood. Perhaps this change in HPA functioning is associated with an
      increased vulnerability for the development of an affective disorder.

PMID- 20148870
TI  - Does lithium protect against dementia?
AB  - OBJECTIVE: To investigate whether treatment with lithium in patients with mania
      or bipolar disorder is associated with a decreased rate of subsequent dementia.
      METHODS: Linkage of register data on prescribed lithium in all patients
      discharged from psychiatric health care service with a diagnosis of mania or
      bipolar disorder and subsequent diagnoses of dementia in Denmark during a period
      from 1995 to 2005. RESULTS: A total of 4,856 patients with a diagnosis of a manic
      or mixed episode or bipolar disorder at their first psychiatric contact were
      included in the study. Among these patients, 2,449 were exposed to lithium
      (50.4%), 1,781 to anticonvulsants (36.7%), 4,280 to antidepressants (88.1%), and
      3,901 to antipsychotics (80.3%) during the study period. A total of 216 patients
      received a diagnosis of dementia during follow-up (103.6/10,000 person-years).
      During the period following the second prescription of lithium, the rate of
      dementia was decreased compared to the period following the first prescription.
      In contrast, the rates of dementia during multiple prescription periods with
      anticonvulsants, antidepressants, or antipsychotics, respectively, were not
      significantly decreased compared to the rate of dementia during the period with
      one prescription of these drugs. CONCLUSIONS: Continued treatment with lithium
      was associated with a reduced rate of dementia in patients with bipolar disorder
      in contrast to continued treatment with anticonvulsants, antidepressants, or
      antipsychotics. Methodological reasons for these findings cannot be excluded due
      to the nonrandomized nature of the data.

PMID- 20148867
TI  - Conceptual and methodological issues in designing a randomized, controlled
      treatment trial for geriatric bipolar disorder: GERI-BD.
AB  - AIM: This report considers the conceptual and methodological concerns confronting
      clinical investigators seeking to generate knowledge regarding the tolerability
      and benefits of pharmacotherapy in geriatric bipolar disorder (BD) patients.
      METHOD: There is continuing need for evidence-based guidelines derived from
      randomized controlled trials that will enhance drug treatment of geriatric BD
      patients. Therefore, we present the complex conceptual and methodological choices
      encountered in designing a multisite clinical trial and the decisions reached by
      the investigators with the intention that study findings be pertinent to, and can
      facilitate, routine treatment decisions. RESULTS: Guided by a literature review
      and input from peers, the tolerability and antimanic effects of lithium and
      valproate were judged to be the key mood stabilizers to investigate with regard
      to treating bipolar I disorder manic, mixed, and hypomanic states. The patient
      selection criteria are intended to generate a sample that not only experiences
      common treatment needs but also represents the variety of older patients seen in
      university-based clinical settings. The clinical protocol guides titration of
      lithium and valproate to target serum concentrations, with lower levels allowed
      when necessitated by limited tolerability. The protocol emphasizes initial
      monotherapy. However, augmentation with risperidone is permitted after three
      weeks when indicated by operational criteria. CONCLUSIONS: A randomized,
      controlled trial that both investigates commonly prescribed mood stabilizers and
      maximizes patient participation can meaningfully address high-priority clinical
      concerns directly relevant to the routine pharmacologic treatment of geriatric BD
      patients.

PMID- 20148871
TI  - N-methyl-D-aspartate receptor expression in parvalbumin-containing inhibitory
      neurons in the prefrontal cortex in bipolar disorder.
AB  - OBJECTIVES: Inhibitory neural circuits and the glutamatergic regulation of these
      circuits in the cerebral cortex appear to be disturbed in bipolar disorder. In
      this study, we addressed the hypothesis that, in the prefrontal cortex (PFC),
      disturbances of glutamatergic regulation of the class of inhibitory neurons that
      contain the calcium buffer parvalbumin (PV) via N-methyl-D-aspartate (NMDA)
      receptor may contribute to the pathophysiology of bipolar disorder. METHODS: We
      used double in situ hybridization with a sulfur-35-labeled riboprobe for the NR2A
      subunit of the NMDA receptor and a digoxigenin-labeled riboprobe for PV in a
      cohort of 18 subjects with bipolar disorder and 18 demographically matched normal
      control subjects. RESULTS: We observed no differences in the relative density and
      laminar distribution of the PV-expressing neurons between subjects with bipolar
      disorder and matched normal control subjects. Furthermore, the density of the PV
      neurons that co-expressed NR2A messenger RNA (mRNA) or the cellular expression of
      NR2A mRNA in the PV neurons that exhibited a detectable level of this transcript
      was unaltered in subjects with bipolar disorder. CONCLUSIONS: These findings
      suggest that, in the PFC, glutamatergic regulation of PV-containing inhibitory
      neurons via NR2A-containing NMDA receptors does not appear to be altered in
      bipolar disorder. However, the possibility that other subsets of gamma
      aminobutyric acid (GABA) neurons or other glutamate receptor subtypes are
      affected cannot be excluded.

PMID- 20148872
TI  - Higher striatal dopamine transporters in euthymic patients with bipolar disorder:
      a SPECT study with [Tc] TRODAT-1.
AB  - OBJECTIVES: Dopamine has been implicated in the etiology of bipolar disorder. The
      aim of this study was to explore striatal dopamine transporter (DAT) availability
      in euthymic bipolar patients. METHODS: Seventeen drug-free euthymic bipolar
      patients were recruited. The availability of DAT was approximated using single
      photon emission computed tomography (SPECT) with [99mTc] TRODAT-1. RESULTS:
      Compared to the controls, the euthymic bipolar patients had significantly higher
      availability of striatal DAT. CONCLUSIONS: Even for patients in the euthymic
      state, the DAT availability is still higher than that of the controls.

PMID- 20148873
TI  - Expression of oligodendrocyte and myelin genes is not altered in peripheral blood
      cells of patients with first-episode schizophrenia and bipolar disorder.

PMID- 20148874
TI  - The future of anticonvulsants in bipolar disorder.

PMID- 20148877
TI  - The t(14;20)(q32;q12): a rare cytogenetic change in multiple myeloma associated
      with poor outcome.

PMID- 20148878
TI  - Long-term, sub-clinical cardiac and renal complications in patients with multiple
      relapses of thrombotic thrombocytopenic purpura.

PMID- 20148879
TI  - Non-homologous end-joining gene profiling reveals distinct expression patterns
      associated with lymphoma and multiple myeloma.
AB  - Repair of DNA strand breaks induced during lymphoid antigen receptor
      rearrangement involves non-homologous end-joining (NHEJ). We investigated NHEJ in
      the aetiology of lymphoproliferative disorders (LPDs) and the disease subtypes
      therein through real-time quantitative RT-PCR gene expression analysis. Lower
      expression of XRCC6 and MRE11A was observed in all tumours, with higher
      expression of both XRCC4 and RAD50 observed only in multiple myeloma (MM).
      Hierarchical clustering enabled tumours to be clearly distinguished from
      controls, and by morphological sub-type. We postulate this identifies targets
      worthy of investigation in the genetic predisposition, pathogenesis and prognosis
      of lymphoid malignancies.

PMID- 20148880
TI  - Genetic susceptibility, smoking, obesity and risk of venous thromboembolism.
AB  - The F5 G1691A (Factor V Leiden) and F2 G20210A (prothrombin) mutations are linked
      to an increase in the incidence rate of venous thromboembolism (VTE), but their
      effects are highly variable. We investigated whether the effects of smoking and
      obesity might explain this variability. In a case-cohort study including the
      participants of the Danish Diet, Cancer and Health study, we computed incidence
      rates and Cox proportional hazard ratios for VTE in individuals with and without
      the mutations, categorized by weight and tobacco consumption. The sole effect of
      heavy smoking was 128 extra VTE events per 100,000 person years in individuals
      with the F5 G1691A mutation versus 59 in individuals without. The sole effect of
      obesity was 222 extra VTE events per 100,000 person years in individuals with the
      F5 G1691A mutation, versus 103 in individuals without this mutation; and 705
      extra VTE events per 100,000 person years in individuals with the F2 G20210A
      mutation versus 107 in individuals without this mutation. The F5 G1691A and F2
      G20210A mutations conferred increased susceptibility to the unfavourable effects
      of smoking and obesity on the risk for VTE. Thus, individuals with genetic risk
      factors for VTE might benefit from maintaining a healthy lifestyle.

PMID- 20148881
TI  - Actin filaments and microtubule dual-granule transport in human adhered
      platelets: the role of alpha-dystrobrevins.
AB  - Upon activation with physiological stimuli, human platelets undergo morphological
      changes, centralizing their organelles and secreting effector molecules at the
      site of vascular injury. Previous studies have indicated that the actin filaments
      and microtubules of suspension-activated platelets play a critical role in
      granule movement and exocytosis; however, the participation of these cytoskeleton
      elements in adhered platelets remains unexplored. alpha- and beta-dystrobrevin
      members of the dystrophin-associated protein complex in muscle and non-muscle
      cells have been described as motor protein receptors that might participate in
      the transport of cellular components in neurons. Recently, we characterized the
      expression of dystrobrevins in platelets; however, their functional diversity
      within this cellular model had not been elucidated. The present study examined
      the contribution of actin filaments and microtubules in granule trafficking
      during the platelet adhesion process using cytoskeleton-disrupting drugs,
      quantification of soluble P-selectin, fluorescence resonance transfer energy
      analysis and immunoprecipitation assays. Likewise, we assessed the interaction of
      alpha-dystrobrevins with the ubiquitous kinesin heavy chain. Our results strongly
      suggest that microtubules and actin filaments participate in the transport of
      alpha and dense granules in the platelet adhesion process, during which alpha
      dystrobrevins play the role of regulatory and adaptor proteins that govern
      trafficking events.

PMID- 20148882
TI  - Venous thrombosis prevention - more than just guidelines.
AB  - Hospital-associated venous thromboembolism remains a major international cause of
      avoidable mortality and morbidity. Although the publication of national
      guidelines does increase the use of thromboprophylaxis, we present the results of
      a recent audit of thrombosis prevention in UK hospitals which, despite published
      guidelines, shows continuing significant variations in guideline implementation
      and practice. The results of this audit are paralleled with UK and international
      data on hospital-acquired thrombosis prevention and the potential solutions to
      these problems, particularly the lessons which can be learned from other areas of
      clinical practice, are discussed.

PMID- 20148884
TI  - Acute lymphoblastic leukaemia in children - is there a role for MTHFR?

PMID- 20148885
TI  - The genotype nucleophosmin mutated and FLT3-ITD negative is characterized by high
      bax/bcl-2 ratio and favourable outcome in acute myeloid leukaemia.
AB  - Nucleophosmin gene (NPM1) mutations characterize acute myeloid leukaemia (AML)
      with normal karyotype and frequently co-exist with FLT3 internal tandem
      duplications (ITD). We evaluated bcl-2, bax, NPM1 and FLT3-ITD in 222 AML
      patients. Bax/bcl-2 ratio >0.35 and NPM1 without FLT3-ITD were significantly
      associated (P = 0.0001). NPM1-mutated (mt)/FLT3-ITD negative patients showed a
      higher complete remission (CR) rate (90%, P = 0.0002) and a longer overall
      survival (OS, P = 0.00007). NPM1-mt/FLT3-ITD negative plus bax/bcl-2 > 0.35
      subset showed a very high CR rate (96%), very long OS (P = 0.00005) and disease
      free survival (P = 0.004). The favourable prognosis of NPM1-mt/FLT3-ITD negative
      patients might be explained by a higher bax/bcl-2 ratio.

PMID- 20148886
TI  - Managing anticoagulated patients during neuraxial anaesthesia.
AB  - The widespread use of central neuraxial block (CNB) and the prevalence of
      anticoagulation for different indications have led to an inevitable overlap
      between the two. The most serious complication of CNB in anticoagulated patients
      is the risk of spinal/epidural haematoma. Performing CNB in these patients is a
      complex decision that should take into account the twin risks of bleeding and
      venous/arterial thrombosis if anticoagulation therapies were to be stopped.
      Various guidelines have been issued to achieve normal haemostasis and thus allow
      safe administration of CNB. However, the evidence base for many such
      recommendations is weak, relying mainly on case reports, small studies and
      pharmacokinetics of the drugs. Given these limitations it is crucial to fully
      assess individual risk factors and understand anticoagulant pharmacokinetics in
      order to appropriately set time intervals for catheter insertion/removal. This
      paper will review traditional and newer anticoagulation/antiplatelet therapies
      with a view to improving the management of anticoagulated patients undergoing
      CNB.

PMID- 20148888
TI  - Monoclonal gammopathy of undetermined significance: to screen or not to screen
      for multiple myeloma?

PMID- 20148887
TI  - Restored platelet function after romiplostim treatment in a patient with immune
      thrombocytopenic purpura.

PMID- 20148889
TI  - Congestive heart failure as presentation of acute lymphoblastic leukaemia with
      eosinophilia.

PMID- 20148890
TI  - Distinct expression and ligand-binding profiles of two constitutively active
      GPR17 splice variants.
AB  - BACKGROUND AND PURPOSE: In humans and non-human primates, the 7TM receptor GPR17
      exists in two isoforms differing only by the length of the N-terminus. Of these,
      only the short isoform has previously been characterized. Hence, we investigated
      gene expression and ligand-binding profiles of both splice variants and
      furthermore uncovered and characterized constitutive activity of both isoforms.
      EXPERIMENTAL APPROACH: Expression levels of the hGPR17 isoforms were determined
      in several brain regions as well as heart and kidney using quantitative RT-PCR. A
      CREB reporter assay and [(35)S]-GTPgammaS binding were employed to assess the
      constitutive activity and the activation by UDP, UDP-glucose and -galactose and
      the cysteinyl leukotrienes LTC(4) and LTD(4). Leukotriene binding and induction
      of internalization were furthermore tested using homologous competition binding
      and antibody-feeding experiments respectively. KEY RESULTS: The short isoform
      (hGPR17-S) was expressed more abundantly (eight- to 23-fold) in the brain than
      the long isoform (hGPR17-L), whereas the opposite was observed in heart and
      kidney. As previously reported, the uracil nucleotides activated hGPR17-S with
      micromolar potencies. However, much lower potencies were observed for hGPR17-L
      with a 50- to 170-fold increase in EC(50). Furthermore, contrary to previous
      reports, neither of the isoforms was activated or bound by the cysteinyl
      leukotrienes. Finally, both receptors were demonstrated to be constitutively
      active through Galpha(i). CONCLUSIONS AND IMPLICATIONS: We present the first
      isoform-specific characterization of GPR17 and show that differences exist
      between the isoforms, in both expression pattern and pharmacological profile. In
      turn, our results indicate that the two human isoforms might serve tissue
      specific functions.

PMID- 20148891
TI  - A structural basis for the inhibition of collagen-stimulated platelet function by
      quercetin and structurally related flavonoids.
AB  - BACKGROUND AND PURPOSE: Molecular mechanisms underlying the links between dietary
      intake of flavonoids and reduced cardiovascular disease risk are only partially
      understood. Key events in the pathogenesis of cardiovascular disease,
      particularly thrombosis, are inhibited by these polyphenolic compounds via
      mechanisms such as inhibition of platelet activation and associated signal
      transduction, attenuation of generation of reactive oxygen species, enhancement
      of nitric oxide production and binding to thromboxane A(2) receptors. In vivo,
      effects of flavonoids are mediated by their metabolites, but the effects and
      modes of action of these compounds are not well-characterized. A good
      understanding of flavonoid structure-activity relationships with regard to
      platelet function is also lacking. EXPERIMENTAL APPROACH: Inhibitory potencies of
      structurally distinct flavonoids (quercetin, apigenin and catechin) and plasma
      metabolites (tamarixetin, quercetin-3'-sulphate and quercetin-3-glucuronide) for
      collagen-stimulated platelet aggregation and 5-hydroxytryptamine secretion were
      measured in human platelets. Tyrosine phosphorylation of total protein, Syk and
      PLCgamma2 (immunoprecipitation and Western blot analyses), and Fyn kinase
      activity were also measured in platelets. Internalization of flavonoids and
      metabolites in a megakaryocytic cell line (MEG-01 cells) was studied by
      fluorescence confocal microscopy. KEY RESULTS: The inhibitory mechanisms of these
      compounds included blocking Fyn kinase activity and the tyrosine phosphorylation
      of Syk and PLCgamma2 following internalization. Principal functional groups
      attributed to potent inhibition were a planar, C-4 carbonyl substituted and C-3
      hydroxylated C ring in addition to a B ring catechol moiety. CONCLUSIONS AND
      IMPLICATIONS: The structure-activity relationship for flavonoids on platelet
      function presented here may be exploited to design selective inhibitors of cell
      signalling.

PMID- 20148892
TI  - Binding of GTPgamma[35S] is regulated by GDP and receptor activation. Studies
      with the nociceptin/orphanin FQ receptor.
AB  - BACKGROUND AND PURPOSE: We have examined the effects of ligand efficacy and
      receptor density on the binding of guanosine 5'-[gamma-thio]triphosphate
      (GTPgammaS) and GDP to the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP)
      coupled G-proteins. EXPERIMENTAL APPROACH: In GTPgamma[(35)S] binding
      experiments, using stable (CHO(hNOP)) and inducible (CHO(INDhNOP)) recombinant
      human and rat NOP we have measured: (i) ligand-specific GDP requirements; (ii)
      the effects of receptor density on guanine nucleotide affinity/capacity; and
      (iii) the effect of ligand efficacy on GTPgammaS association kinetics. KEY
      RESULTS: GTPgammaS competition curves were shallow and modelled by high- and low
      affinity components that were relatively consistent between cell types and tissue
      preparations. In the presence of 1 microM N/OFQ a high-affinity GDP binding site
      was also present, but the fraction of total binding was reduced. In an efficacy
      dependent manner, the partial agonists [F/G]N/OFQ(1-13)NH(2) ([Phe(1)psi(CH(2)
      NH)Gly(2)]-nociceptin(1-13)NH(2)) and naloxone benzoylhydrazone both reduced the
      fraction of high-affinity sites for GDP (relative to basal). While the pIC(50)
      for high-affinity GDP binding site did not decrease in the presence of 1 microM
      N/OFQ, N/OFQ produced a significant reduction in pIC(50) for the low-affinity
      site. Agonist-mediated decrease in affinity for GDP binding was efficacy
      dependent. GDP displayed three affinities: high, conserved in the presence and
      absence of ligand; intermediate, present as a low fraction under basal
      conditions; low (efficacy-dependent), present during receptor activation
      representing the majority of binding. CONCLUSIONS AND IMPLICATIONS: The affinity
      of GTPgamma[(35)S] was regulated by GDP and receptor activation caused increased
      binding of GTPgamma[(35)S] through a reduction in GDP affinity.

PMID- 20148893
TI  - Pigpen, a nuclear coiled body component protein, is involved in angiogenesis.
AB  - We previously reported that puromycin-insensitive leucyl-specific aminopeptidase
      (PILSAP) is required for vascular endothelial growth factor (VEGF)- and basic
      fibroblast growth factor (bFGF)-induced angiogenesis and for endothelial
      differentiation from embryonic stem (ES) cells via the aminopeptidase activity of
      PILSAP. In this study, we searched for molecules that function during
      angiogenesis with PILSAP. We performed proteome analysis of nuclear extracts from
      embryoid bodies (EBs) made from ES cells transfected with mutant PILSAP lacking
      aminopeptidase activity and mock EBs. We identified pigpen, a 67-kDa nuclear
      coiled body component protein. Immunoprecipitation and western blotting
      demonstrated the binding of PILSAP and pigpen in endothelial cells (ECs), and
      this interaction was enhanced by VEGF and bFGF. Pigpen was reported to be
      expressed in actively growing ECs such as those in embryos and tumors. However,
      whether Pigpen is involved in angiogenesis is not known. Therefore, we examined
      the effect of pigpen on angiogenesis by silencing pigpen with siRNA (siPigpen).
      Compared with scrambled RNA (scrPigpen), transfection of siPigpen into mouse ECs
      inhibited proliferation, migration, and network formation. These results were
      confirmed with other two siRNAs. Moreover, siPigpen suppressed bFGF-induced
      angiogenesis in a Matrigel plug assay, and injection of siPigpen into Lewis lung
      carcinoma cell tumors implanted subcutaneously into 5-week-old C57/BL male mice
      prevented tumor growth and tumor angiogenesis. These data indicate that Pigpen is
      involved in angiogenesis and that pigpen may be a target for blocking tumor
      angiogenesis.

PMID- 20148894
TI  - Coordinate action of membrane-type matrix metalloproteinase-1 (MT1-MMP) and MMP-2
      enhances pericellular proteolysis and invasion.
AB  - Membrane-type matrix metalloproteinase-1 (MT1-MMP) mediates cleavage of not only
      MMP-2/gelatinase A for activation, but also a variety of substrates including
      type I collagen (reviewed in Cancer Sci 2005; 96: 212-7). MMP-2 activation
      involves tissue inhibitor of MMP (TIMP)-2 as a bridging molecule between MT1-MMP
      and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex
      manner depending on TIMP-2 concentration. During invasive growth of tumor cells
      in type I collagen matrix, MT1-MMP initiates denaturation of collagen into
      gelatin, which is subsequently digested further by MMP-2 adjacent to MT1-MMP.
      Coordinate action of MT1-MMP and MMP-2 may facilitate pericellular proteolysis,
      and enhance not only tumor invasion/migration but also cell growth. Tetraspanins
      as binding proteins of MT1-MMP regulate MT1-MMP subcellular localization and
      compartmentalization, leading to efficient MMP-2 activation and proteolysis
      coupled with cellular function.

PMID- 20148895
TI  - Anti-miR-21 oligonucleotide sensitizes leukemic K562 cells to arsenic trioxide by
      inducing apoptosis.
AB  - Arsenic trioxide (ATO), an ancient traditional Chinese medicine, has been
      successfully used as a therapeutic agent for leukemia. Drug resistance and
      toxicity are major concerns with the treatment. MicroRNAs (miRNAs) are endogenous
      small non-coding RNA molecules that might modulate cellular sensitivity to
      anticancer drugs. miRNA-21 (miR-21) is one of the most prominent miRNAs involved
      in various aspects of human cancers. However, miR-21 has been rarely
      characterized in chronic myelogenous leukemia (CML). Here, we used a specific
      anti-miR-21 oligonucleotide (AMO-miR-21) to sensitize K562 cells to ATO by
      degradation of miR-21. The results showed that both AMO-miR-21 and ATO caused
      growth inhibition, apoptosis, and G1-phase arrest in K562 cells. Meanwhile, AMO
      miR-21 significantly promoted ATO-mediated growth inhibition and apotosis without
      affecting the G1 phase. Apoptotic cells were confirmed morphologically with
      Giemsa's staining. Furthermore, dual-luciferase reporter vector, containing two
      tandem miR-21 binding sites from PDCD4 3'UTR, validated that PDCD4 was directly
      regulated by miR-21. Therefore, AMO-miR-21 sensitized leukemic K562 cells to ATO
      by inducing apoptosis partially due to its up-regulation of PDCD4 protein level.
      The combination of ATO and AMO-miR-21 present therapeutic potential for CML.

PMID- 20148896
TI  - Microtubule-dependent retrograde transport of bovine immunodeficiency virus.
AB  - Microtubules are essential components of the cytoskeleton that participate in a
      variety of cellular processes such as cell division and migration. In addition,
      there is a growing body of evidence implicating a role for microtubules in
      intracellular viral transport. In this study, we found that pharmacological
      disruption of microtubules remarkably blocked bovine immunodeficiency virus (BIV)
      movement from the cell periphery to the perinuclear region, a process known as
      retrograde transport. A similar effect was observed by inhibiting function of the
      microtubule-associated motor protein dynein. By yeast two-hybrid assay, we found
      that the capsid protein (CA) of BIV interacted with the dynein light-chain
      component LC8. Immunoprecipitation and GST-pulldown assays further demonstrated
      an interaction between CA and LC8 in mammalian cells. In addition, our data
      revealed LC8 as a linker between BIV particles and microtubules. Retrograde
      transport of BIV was significantly inhibited by knockdown of LC8 expression. Our
      findings present the first evidence that incoming BIV particles employ host
      microtubule/dynein machinery for transport towards the perinuclear region. In
      addition, our data indicate that the LC8-CA interaction is a potential target for
      the design of antiviral strategies.

PMID- 20148897
TI  - LnaB: a Legionella pneumophila activator of NF-kappaB.
AB  - Legionella pneumophila possesses a large arsenal of type IV translocated
      substrates. Over 100 such proteins have been identified, but the functions of
      most are unknown. Previous studies have demonstrated that L. pneumophila
      activates NF-kappaB, a master transcriptional regulator of the mammalian innate
      immune response. Activation of NF-kappaB is dependent on the Legionella Icm/Dot
      type IV protein translocation system, consistent with the possibility that
      translocated bacterial proteins contribute to this response. To test this
      hypothesis, an expression library of 159 known and putative translocated
      substrates was created to evaluate whether ectopic production of a single L.
      pneumophila protein could activate NF-kappaB in mammalian cells. Expression of
      two of these proteins, LnaB (Legionella NF-kappaB activator B) and LegK1,
      resulted in approximately 150-fold induction of NF-kappaB activity in HEK293T
      cells, levels similar to the strong induction that occurs with ectopic expression
      of the known activator Nod1. LnaB is a substrate of the Icm/Dot system, and in
      the absence of this protein, a partial reduction of NF-kappaB activation in host
      cells occurs after challenge by post-exponential phase bacteria. These data
      indicate that LnaB is an Icm/Dot substrate that contributes to NF-kappaB
      activation during L. pneumophila infection in host cells.

PMID- 20148898
TI  - The presence of professional phagocytes dictates the number of host cells
      targeted for Yop translocation during infection.
AB  - Type III secretion systems deliver effector proteins from Gram-negative bacterial
      pathogens into host cells, where they disarm host defences, allowing the
      pathogens to establish infection. Although Yersinia pseudotuberculosis delivers
      its effector proteins, called Yops, into numerous cell types grown in culture, we
      show that during infection Y. pseudotuberculosis selectively targets Yops to
      professional phagocytes in Peyer's patches, mesenteric lymph nodes and spleen,
      although it colocalizes with B and T cells as well as professional phagocytes.
      Strikingly, in the absence of neutrophils, the number of cells with translocated
      Yops was significantly reduced although the bacterial loads were similar,
      indicating that Y. pseudotuberculosis did not arbitrarily deliver Yops to the
      available cells. Using isolated splenocytes, selective binding and selective
      targeting to professional phagocytes when bacteria were limiting was also
      observed, indicating that tissue architecture was not required for the tropism
      for professional phagocytes. In isolated splenocytes, YadA and Invasin increased
      the number of all cells types with translocated Yops, but professional phagocytes
      were still preferentially translocated with Yops in the absence of these
      adhesins. Together these results indicate that Y. pseudotuberculosis
      discriminates among cells it encounters during infection and selectively delivers
      Yops to phagocytes while refraining from translocation to other cell types.

PMID- 20148899
TI  - Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC
      inflammasome.
AB  - Interleukin-1beta (IL-1beta) represents one of the most important mediators of
      inflammation and host responses to infection. Mycobacterium tuberculosis (Mtb),
      the causative agent of human tuberculosis, induces IL-1beta secretion at the site
      of infection, but the underlying mechanism(s) are poorly understood. In this work
      we show that Mtb infection of macrophages stimulates caspase-1 activity and
      promotes the secretion of IL-1beta. This stimulation requires live intracellular
      bacteria expressing a functional ESX-1 secretion system. ESAT-6, an ESX-1
      substrate implicated in membrane damage, is both necessary and sufficient for
      caspase-1 activation and IL-1beta secretion. ESAT-6 promotes the access of other
      immunostimulatory agents such as AG85 into the macrophage cytosol, indicating
      that this protein may contribute to caspase-1 activation largely by perturbing
      host cell membranes. Using a high-throughput shRNA-based screen we found that
      numerous NOD-like receptors (NLRs) and CARD domain-containing proteins (CARDs)
      were important for IL-1beta secretion upon Mtb infection. Most importantly,
      NLRP3, ASC and caspase-1 form an infection-inducible inflammasome complex that is
      essential for IL-1beta secretion. In summary, we show that recognition of Mtb
      infection by the NLRP3 inflammasome requires the activity of the bacterial
      virulence factor ESAT-6, and the subsequent IL-1beta response is regulated by a
      number of NLR/CARD proteins.

PMID- 20148900
TI  - Entamoeba histolytica sirtuin EhSir2a deacetylates tubulin and regulates the
      number of microtubular assemblies during the cell cycle.
AB  - We have discovered four sirtuin genes in Entamoeba histolytica, two of which are
      similar to eukaryotic sirtuins and two to bacterial and archaeal sirtuins. The
      eukaryotic sirtuin homologue, EhSir2a, showed NAD(+)-dependent deacetylase
      activity and was sensitive to class III HDAC inhibitors. Localization of EhSir2a
      at different cellular sites suggested that this deacetylase could have multiple
      targets. Using an E. histolytica cDNA library in the yeast two-hybrid genetic
      screen, we identified several proteins that bound to EhSir2a. These proteins
      included Eh alpha-tubulin, whose interaction with EhSir2a was validated in E.
      histolytica. We have shown that EhSir2a deacetylated tubulin and localized with
      microtubules in E. histolytica. Increased expression levels of EhSir2a in stable
      transformants led to reduced number of microtubular assemblies in serum
      synchronized cells. This effect was abrogated by mutations in the deacetylase
      domain of EhSir2a, showing that EhSir2a deacetylase activity affected the
      stability and number of microtubular assemblies during the cell cycle of E.
      histolytica. Our results suggest that epigenetic modification of tubulin by
      EhSir2a is one of the mechanisms that regulates microtubular assembly in E.
      histolytica.

PMID- 20148903
TI  - Synthesis and antimycobacterial evaluation of novel Phthalazin-4-ylacetamides
      against log- and starved phase cultures.
AB  - Twenty four novel 2-[3-(4-bromo-2-fluorobenzyl)-4-oxo-3,4-dihydro-1
      phthalazinyl]acetic acid amides were synthesized from phthalic anhydride and were
      subjected to in vitro and in vivo evaluation against log- and starved phase of
      mycobacterial species and Mycobacterium tuberculosis isocitrate lyase enzyme
      inhibition studies. Among the compounds screened, 2-(2-(4-bromo-2-fluorobenzyl)
      1,2-dihydro-1-oxophthalazin-4-yl)-N-(2,6-dimethylphenyl)acetamide (5j) inhibited
      all eight mycobacterial species with MIC's ranging from 0.08 to 5.05 microm and
      was non-toxic to Vero cells till 126.43 microm. Four compounds were tested
      against starved culture of Mycobacterium tuberculosis and they inhibited with
      MIC's ranging from 3.78 to 23.2 microm. Some compounds showed 40-66% inhibition
      against Mycobacterium tuberculosis isocitrate lyase enzyme at 10 microm. The
      docking studies also confirmed the binding potential of the compounds at the
      isocitrate lyase active site. In the in vivo animal model, 5j reduced the
      mycobacterial load in lung and spleen tissues with 1.38 and 2.9-log10
      protections, respectively, at 25 mg/kg body weight dose.

PMID- 20148901
TI  - ROS-inhibitory activity of YopE is required for full virulence of Yersinia in
      mice.
AB  - YopE, a type III secreted effector of Yersinia, is a GTPase Activating Protein
      for Rac1 and RhoA whose catalytic activity is critical for virulence. We found
      that YopE also inhibited reactive oxygen species (ROS) production and inactivated
      Rac2. How YopE distinguishes among its targets and which specific targets are
      critical for Yersinia survival in different tissues are unknown. A screen
      identifying YopE mutants in Yersinia pseudotuberculosis that interact with
      different Rho GTPases showed that YopE residues at positions 102, 106, 109 and
      156 discern among switch I and II regions of Rac1, Rac2 and RhoA. Two mutants,
      which expressed YopE alleles with different antiphagocytic, ROS-inhibitory and
      cell-rounding activities, YptbL109A and YptbESptP, were studied in animal
      infections. Inhibition of both phagocytosis and ROS production were required for
      splenic colonization, whereas fewer YopE activities were required for Peyer's
      patch colonization. This study shows that Y. pseudotuberculosis encounters
      multiple host defences in different tissues and uses distinct YopE activities to
      disable them.

PMID- 20148904
TI  - Riboflavin biosynthetic and regulatory factors as potential novel anti-infective
      drug targets.
AB  - Riboflavin (vitamin B2) is the direct precursor of redox enzyme cofactors flavin
      mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential
      for multiple cell physiology. The riboflavin biosynthetic pathway is regarded as
      a rich resource for therapeutic targets for broad spectrum antibiotics. Enzymatic
      pathways, regulatory factors of the riboflavin biosynthesis, and relevant drug
      discovery are summarized in this review. The novel riboswitch regulatory
      mechanism of riboflavin metabolism is also described. A compendium of chemical
      modulators of riboflavin biosynthesis and regulatory networks is listed and such
      demonstrates the promise of riboflavin biosynthesis and regulatory mechanisms as
      potential therapeutic targets for novel antibiotic drug discovery.

PMID- 20148905
TI  - Thyroid dysfunction in a UK hepatitis C population treated with interferon-alpha
      and ribavirin combination therapy.
AB  - OBJECTIVE: To assess the incidence of thyroid dysfunction (TD) in a UK cohort of
      patients with hepatitis C virus (HCV) infection treated with interferon-alpha
      (IFNalpha) and ribavirin combination therapy (IFN/RBV). DESIGN, PATIENTS AND
      MEASUREMENTS: A retrospective study of 288 patients who received IFN/RBV for HCV
      during a 2-year period from January 2006 was performed. Thyroid function was
      assessed during a 24-week or 48-week course of IFN/RBV. If serum thyrotrophin
      (TSH) became undetectable (<0.01 mU/l) and serum free thyroxine (T4) was raised,
      a diagnostic thyroid isotope scan was performed. RESULTS: Full medical records
      were examined for 260 patients (172 men, 88 women) included in the study, of whom
      22.3% (16.9% of men, 33.0% of women) developed TD during IFN/RBV. In total, 10.4%
      developed a suppressed serum TSH (0.8% Graves' disease, 9.6% transient
      thyroiditis) while 11.9% developed an elevated serum TSH with 1.5% becoming
      permanently hypothyroid and requiring levothyroxine therapy. Women had a relative
      risk (RR) for developing TD of 1.96 (CI: 1.75-3.03, P = 0.004). A serum TSH > or
      =1.75 mU/l and a positive thyroid peroxidase (TPO) antibody titre pretherapy were
      associated with RRs for progression to TD of 6.02 (CI: 2.95-12.78, P < 0.0001)
      and 4.35 (CI: 2.58-6.52; P < 0.0001), respectively, while combination of baseline
      TSH and TPO antibody data predicted progression to TD with a sensitivity of
      94.7%. CONCLUSIONS: Although TD was common in this cohort, just 2.3% developed TD
      that required ongoing therapy. Pre-IFN/RBV serum TSH and TPO antibody titre were
      found to predict progression to TD in this group of patients.

PMID- 20148907
TI  - What to do for moderate-to-severe and active Graves' orbitopathy if
      glucocorticoids fail?
AB  - Treatment of Graves' orbitopathy (GO) is a major challenge, and the outcome of
      medical therapy is unsatisfactory in about one-third of cases. Glucocorticoids
      are the first-line therapy for moderate-to-severe and active GO, more commonly
      given through the intravenous route. Uncertainty remains as to the best
      therapeutic approach when the initial glucocorticoid treatment provides an
      incomplete response or no response. The choice largely depends on personal
      experience because of the limited evidence in this field. In the author's view,
      if a first course of glucocorticoids provides a suboptimal response, a second
      course of intravenous (or oral) glucocorticoids associated with orbital
      radiotherapy should be given. An alternative might be represented by oral
      glucocorticoids associated with cyclosporine. The use of biological agents, the
      most promising being rituximab, is for the time being experimental and warrants
      support from randomized clinical trials.

PMID- 20148906
TI  - Effects of rosiglitazone on bone mineral density and remodelling parameters in
      Postmenopausal diabetic women: a 2-year follow-up study.
AB  - OBJECTIVE: To evaluate the effect of rosiglitazone on bone metabolism and bone
      density. DESIGN: An open-label, randomized, controlled trial of 24-month
      duration. Patients and measurements Obese, postmenopausal women with newly
      diagnosed diabetes were studied. Before and after the intervention, metabolic
      bone markers and bone density were assessed. RESULTS: Twenty-six patients
      received rosiglitazone (4 mg/day), and 23 remained on diet alone. Serum bone
      specific alkaline phosphatase and osteocalcin levels decreased by 17% (P < 0.001
      vs control group) and 26% (P < 0.01 vs control group), respectively, in the
      rosiglitazone group. There were no significant changes in the deoxypyridinoline
      levels between the two groups. Annual bone loss at the trochanter and at the
      lumbar spine associated with each year of rosiglitazone use was 2.56% (P = 0.01
      vs control group) and 2.18% (P < 0.01 vs control group), respectively. Femoral
      neck and total hip bone density declined significantly in both groups (P < 0.01,
      and P = 0.01, respectively) but was not significantly different between the two
      groups. CONCLUSIONS: Rosiglitazone treatment adversely affects bone formation
      over a 2-year period. It increases bone loss at the lumbar spine and trochanter
      in postmenopausal, type 2 diabetic women. However, bone loss at the total hip did
      not differ with use of this agent.

PMID- 20148908
TI  - Influence of parental origin of the X chromosome on physical phenotypes and GH
      responsiveness of patients with Turner syndrome.
AB  - OBJECTIVE: Previous studies have reported the effects of parental origin of the X
      chromosome on specific phenotypic and cognitive profiles in Turner syndrome (TS).
      Here, we investigate the possible parent-of-origin effects on physical phenotypes
      and responsiveness to GH in Korean patients with TS. DESIGN AND PATIENTS: Thirty
      three patients with TS with nonmosaic karyotype and their parents participated in
      this study. The parental origin of the normal X chromosome was determined by
      comparing parental DNA polymorphisms using nine highly polymorphic microsatellite
      markers on the X chromosome. For the evaluation of parent-of-origin effects,
      typical phenotypic traits, including congenital malformations, auxological and
      endocrinological profiles, were compared. RESULTS: The retained X chromosome was
      of maternal (X(m)) origin in 60.6% patients and paternal (X(p)) origin in 39.4%
      patients. No significant parent-of-origin effects on stature, body mass index,
      cardiac, renal, skeletal, lymphatic, hearing or ocular systems were evident. We
      observed no differences in height gain after GH treatment. In patients with the
      45,X karyotype, patient height was positively correlated with maternal height in
      the X(m) group (r = 0.60, P = 0.04). Moreover, patient height was more
      significantly correlated with maternal than paternal height, irrespective of the
      parental origin of the retained X chromosome. CONCLUSION: While we observed no
      significant impact of parental origin of the X chromosome on several phenotypic
      traits in patients with TS, a maternal imprinting effect on stature was suggested
      at least in patients with 45,X. Further studies on a larger number of patients
      with TS are essential to define the potential imprinting effects of undetermined
      genes on the X chromosome.

PMID- 20148909
TI  - Does leptin predict incident hypertension in older adults?
AB  - OBJECTIVE: Leptin is associated with blood pressure (BP) in experimental and
      cross-sectional studies, but only one previous prospective study of middle-aged
      men has reported the association between leptin and incident hypertension. We
      examined the association of leptin levels with incident hypertension in a
      population-based study of older men and women. DESIGN: Longitudinal cohort study.
      POPULATION: Participants were 602 community-dwelling older adults with normal
      baseline BP levels who attended a research clinic visit between 1984 and 1987 and
      again 4.4 years later (mean age was 66.2 +/- 11.4; 60.6% were men; mean body mass
      index (BMI) 24.9 +/- 3.4 kg/m(2)). MEASUREMENTS: Hypertension was defined as
      systolic BP > or =140 mmHg and/or diastolic BP > or =90 mmHg and/or
      antihypertensive drug treatment. Leptin was measured by radioimmunoassay.
      RESULTS: After an average 4.4-year follow-up (minimum 2-maximum 7 years), 106
      (17.6%) new cases of hypertension were identified. At baseline, participants who
      developed hypertension were older and had higher systolic BP and higher total
      cholesterol compared to participants who remained normotensive. Baseline serum
      leptin levels were higher in participants who developed hypertension compared to
      persistent normotensives [median (25th-75th range)] [8.8(5-16) vs 7(4-11) ng/ml,
      P = 0.002]. In logistic regression models, leptin (log-transformed) predicted
      incident hypertension before and after adjustments for baseline age, BMI,
      systolic BP, total cholesterol, medications, and previous cardiovascular disease
      (OR 1.75 95% CI 1.17-2.61, P = 0.006). This association persisted after exclusion
      of 45 obese participants. CONCLUSION: Higher leptin levels were independently
      associated with increased odds of incident hypertension in older adults.

PMID- 20148910
TI  - Association of FcGRIIa with Graves' disease: a potential role for dysregulated
      autoantibody clearance in disease onset/progression.
AB  - OBJECTIVE: Although autoantibody production is a key feature of autoimmunity, it
      is not known whether variation in autoantibody production and clearance pathways
      is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa)
      molecule is involved in the clearance of autoantibodies and a functional single
      nucleotide polymorphism (SNP), rs1801274, which has been shown to alter
      autoantibody clearance, has been associated with a number of autoimmune diseases
      (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study
      aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the
      UK Caucasian population by Tag SNP screening common polymorphisms within the
      FcGRIIa region. DESIGN: A case control association study investigating nine Tag
      SNPs within FcGRIIa, which captured the majority of known common variation within
      this gene region. PATIENTS: A dataset comprising 2504 UK Caucasian GD patients
      and 2784 geographically matched controls taken from the 1958 British Birth
      cohort. MEASUREMENTS: We used the chi(2)-test to investigate association between
      the Tag SNPs and GD. RESULTS: Association between the rs1801274 (P = 0.003, OR =
      1.12 [95% CI = 1.03-1.22] and rs6427598 (P = 0.012, OR = 0.90 [95% CI = 0.83
      0.98]) SNPs and GD was observed. No other SNPs showed association with GD. No
      associations were seen between any of the SNPs investigated and specific GD
      clinical phenotypes. CONCLUSIONS: This study suggests that variation in FcGRIIa
      predisposes to GD and further supports the role of FcGRIIa as a susceptibility
      locus for AIDs in general.

PMID- 20148911
TI  - Discrepant influence of vitamin D status on parathyroid hormone and bone mass
      after two years of calcium supplementation.
AB  - OBJECTIVE: To investigate the influence of vitamin D status on parathyroid
      hormone and bone mass after a 2-year supplementation of calcium alone. PATIENTS
      AND METHODS: Randomized, double-blind, placebo-controlled clinical trial, in
      healthy postmenopausal women without osteoporosis: three hundred and thirty-six
      subjects aged 60-97 years were studied and randomized to receive elemental
      calcium 500 mg/day (n = 175) or placebo (n = 161) for 2 years. MEASUREMENTS:
      Changes in parathyroid hormone (PTH) and bone mineral density (BMD) from baseline
      and vitamin D status. Values are presented as means +/- SD. RESULTS: After 2
      years, subjects with calcium supplementation had significant decrease in plasma
      PTH level (4.4 +/- 1.7 vs 4.7 +/- 1.9 pmol/l, P < 0.01), improved lumbar BMD
      (1.031 +/- 0.12 vs 1.004 +/- 0.12 g/cm(2), P < 0.001) and total hip BMD (0.890 +/
      0.10 vs 0.883 +/- 0.10 g/cm(2), P < 0.001) without change in femoral neck BMD.
      In the placebo group, PTH level significantly increased (4.8 +/- 1.6 vs 4.5 +/-
      1.5 pmol/l, P < 0.001), lumbar BMD slightly increased (1.027 +/- 0.14 vs 1.018 +/
      0.14 g/cm(2), P < 0.001), total hip and femoral neck BMD decreased (0.876 +/-
      0.11 vs 0.887 +/- 0.11 g/cm(2), P < 0.001 and 0.783 +/- 0.10 vs 0.798 +/- 0.10
      g/cm(2), P < 0.001, respectively). When subjects were classified according to
      baseline 25-hydroxyvitamin D [25(OH)D] levels into those with 25(OH)D in the
      lower tertile (lowVitD) and those in the middle and upper tertiles combined
      (normVitD). The degree of PTH suppression after calcium supplementation was
      significantly higher in the normVitD compared to the lowVitD groups (-5.6 +/-
      26.7%vs 1.3 +/- 27.2%, P < 0.05). No effect of vitamin D status on the change in
      lumbar BMD after calcium supplementation was demonstrated. Despite the higher
      suppression of PTH, there was a slight decrease in femoral neck BMD after calcium
      supplementation in the normVitD group while femoral neck BMD was more or less
      maintained in the lowVitD group (-0.6 +/- 3.2%vs 0.5 +/- 2.9%, P < 0.05).
      CONCLUSION: Calcium supplementation appears to affect femoral bone mass less in
      Thai postmenopausal women with adequate vitamin D status, despite higher
      suppression of PTH.

PMID- 20148912
TI  - Long-chain polyunsaturated fatty acids are consumed during allergic inflammation
      and affect T helper type 1 (Th1)- and Th2-mediated hypersensitivity differently.
AB  - Studies have shown that atopic individuals have decreased serum levels of n-3
      fatty acids. Indicating these compounds may have a protective effect against
      allergic reaction and/or are consumed during inflammation. This study
      investigated whether fish (n-3) or sunflower (n-6) oil supplementation affected T
      helper type 1 (Th1)- and Th2-mediated hypersensitivity in the skin and airways,
      respectively, and whether the fatty acid serum profile changed during the
      inflammatory response. Mice were fed regular chow, chow + 10% fish oil or chow +
      10% sunflower oil. Mice were immunized with ovalbumin (OVA) resolved in Th1 or
      Th2 adjuvant. For Th1 hypersensitivity, mice were challenged with OVA in the
      footpad. Footpad swelling, OVA-induced lymphocyte proliferation and cytokine
      production in the draining lymph node were evaluated. In the airway
      hypersensitivity model (Th2), mice were challenged intranasally with OVA and the
      resulting serum immunoglobulin (Ig)E and eosinophilic lung infiltration were
      measured. In the Th1 model, OVA-specific T cells proliferated less and produced
      less interferon (IFN)-gamma, tumour necrosis factor (TNF) and interleukin (IL)-6
      in fish oil-fed mice versus controls. Footpad swelling was reduced marginally. In
      contrast, mice fed fish oil in the Th2 model produced more OVA-specific IgE and
      had slightly higher proportions of eosinophils in lung infiltrate. A significant
      fall in serum levels of long-chain n-3 fatty acids accompanied challenge and Th2
      mediated inflammation in Th2 model. Fish oil supplementation affects Th1 and Th2
      immune responses conversely; significant consumption of n-3 fatty acids occurs
      during Th2-driven inflammation. The latter observation may explain the
      association between Th2-mediated inflammation and low serum levels of n-3 fatty
      acids.

PMID- 20148913
TI  - Interleukin-10 inhibits Mycobacterium bovis bacillus Calmette-Guerin (BCG)
      induced macrophage cytotoxicity against bladder cancer cells.
AB  - The mechanisms underlying bacillus Calmette-Guerin (BCG) immunotherapy of bladder
      cancer currently remain elusive. Previously, we demonstrated that macrophages
      were cytotoxic to bladder cancer cells upon BCG stimulation in vitro. However,
      macrophages from C57BL/6 mice were less potent than those from C3H/HeN mice for
      the killing of bladder cancer cells. This study was to determine whether
      interleukin (IL)-10 produced by macrophages in response to BCG is a causative
      factor for the reduced cytotoxicity in BCG-stimulated C57BL/6 macrophages.
      Thioglycollate-elicited peritoneal macrophages were prepared and analysed for the
      BCG induction of cytotoxicity, cytokines and nitric oxide (NO) in vitro. Compared
      to BCG-stimulated C3H/HeN macrophages, BCG-stimulated C57BL/6 macrophages
      exhibited reduced killing of bladder cancer MBT-2 cells and MB49 cells. Studies
      demonstrated further that BCG-stimulated C57BL/6 macrophages produced a high
      level of IL-10, which correlated with reduced production of tumour necrosis
      factor (TNF)-alpha, IL-6 and NO. Neutralizing endogenous IL-10 during BCG
      stimulation increased C57BL/6 macrophage cytotoxicity against MB49 cells by 3.2
      fold, along with increased production of TNF-alpha by 6.4-fold and NO by 3.6
      fold, respectively. Macrophages from C57BL/6 IL-10(-/-) mice also exhibited
      increased killing of MB49 cells and production of TNF-alpha and NO upon BCG
      stimulation. In addition, supplementation of exogenous recombinant IL-10 reduced
      BCG-induced C3H/HeN macrophage cytotoxicity against both MBT-2 cells and MB49
      cells in a dose-dependent manner. These results reveal the inhibitory role of IL
      10 in BCG-induced macrophage cytotoxicity, suggesting that blockage of IL-10 may
      potentially enhance the effect of BCG in the treatment of bladder cancer
      patients.

PMID- 20148915
TI  - Scanning electron microscopy observations of failures of implant overdenture
      bars: a case series report.
AB  - BACKGROUND: Soldered or cast bars are used as a standard of care in attachment
      systems supporting maxillary and mandibular implant overdentures. When failures
      of these bars occur, currently there is a lack of evidence in relation to their
      specific etiology, location, or nature. PURPOSE: To investigate the failure
      process of a case series of six failed soldered bars, four intact soldered bars,
      and one intact cast milled bar, which had been supporting implant overdentures.
      MATERIALS AND METHODS: A total of 11 different overdenture bars were removed from
      patients with different configuration of opposing arches. A failed bar (FB) group
      (n = 6) had failed soldered overdenture bars, which were recovered from patients
      following up to 2 years of wear before requiring prosthodontic maintenance and
      repair. An intact bar (IB) group (n = 5) had both soldered bars and a single cast
      milled bar, which had been worn by patients for 2 to 5 years prior to receiving
      other aspects of prosthodontic maintenance. All bars were examined using scanning
      electron microscopy to establish the possible mode of failure (FB) or to identify
      evidence of potential failure in the future (IB). RESULTS: Evidence of a
      progressive failure mode of corrosion fatigue and creep were observed on all the
      FB and IB usually around the solder areas and nonoxidizing gold cylinder. Fatigue
      and creep were also observed in all the IB. Where the level of corrosion was
      substantial, there was no evidence of wear from the matrices of the attachment
      system. Evidence of an instantaneous failure mode, ductile and brittle overload,
      was observed on the fracture surfaces of all the FB, within the solder and the
      nonoxidizing gold cylinders, at the solder/cylinder interface. CONCLUSION:
      Corrosion, followed by corrosion fatigue, appears to be a key factor in the onset
      of the failure process for overdenture bars in this case series of both maxillary
      and mandibular overdentures. Limited sample size and lack of standardization
      identify trends only but prevent broad interpretation of the findings.

PMID- 20148914
TI  - CCR6 identifies lymphoid tissue inducer cells within cryptopatches.
AB  - The chemokine receptor CCR6 is expressed by dendritic cells, B and T cells
      predominantly within the organized structures of the gut-associated lymphatic
      tissue. Its ligand CCL20 is synthesized by the follicle-associated epithelium and
      is crucial for the development of M cells within Peyer's patches. In addition,
      lineage-negative c-kit positive lymphocytes within cryptopatches (CP) express
      CCR6. CCR6-deficient mice exhibit an altered intestinal immune system containing
      increased amounts of intraepithelial lymphocytes and show smaller Peyer's
      patches, while progression of cryptopatches to mature isolated lymphoid follicles
      (ILF) is inhibited. In this report, we show that lin(-) c-kit(+) lymphocytes
      express a variety of different chemokine receptors and that CCR6 identifies those
      cells located within CP. In contrast, cells found outside CP are positive for
      CXCR3 and exhibit a different surface marker profile, suggesting that at least
      two different populations of lin(-) c-kit(+) cells are present. The presence of
      CCR6 does not influence the expression of Notch molecules on lin(-) c-kit(+)
      cells, nor does it influence Notch ligand expression on bone marrow-derived
      dendritic cells. In the human gut, CCR6 identifies clusters of lymphocytes
      resembling murine CP. CCR6 seems to have an important role for lin(-) c-kit(+)
      cells inside CP, is expressed in a regulated manner and identifies potential
      human CP.

PMID- 20148916
TI  - Immediate occlusal loading of NanoTite PREVAIL implants: a prospective 1-year
      clinical and radiographic study.
AB  - BACKGROUND: Recently, a new implant surface texture, featuring application of
      nanometer-scale calcium phosphate has been shown to enhance early bone fixation
      and formation in preclinical studies and in human histomorphometric studies,
      which may be beneficial in immediate loading situations. AIM: The purpose of the
      present prospective clinical study was to, during 1 year, clinically and
      radiographically evaluate a nanometer scale surface modified implant placed for
      immediate loading of fixed prostheses in both maxillary and mandibular regions.
      MATERIALS AND METHODS: Thirty-five out of 38 patients who needed implant
      treatment and met inclusion criteria agreed to participate in the study and were
      consecutively enrolled. Surgical implant placement requirements consisted of a
      final torque of a least 25 Ncm prior to final seating and an implant stability
      quotient above 55. A total of 102 NanoTite PREVAIL (NTP) implants (BIOMET 3i,
      Palm Beach Gardens, FL, USA) (66 maxillary and 36 mandibular) were placed by one
      investigator, and the majority of these were placed in posterior regions (65%)
      and in soft bone (69%). A total of 44 prosthetic constructions were evaluated
      consisting of 14 single-tooth restorations, 26 fixed partial dentures, and four
      complete fixed restorations. All provisional constructions were delivered within
      1 hour, and the final constructions placed after 4 months. Implants were
      monitored for clinical and radiographic outcomes at follow-up examinations
      scheduled for 3, 6, and 12 months. RESULTS: Of the 102 study implants, one
      implant failed. The simple cumulative survival rate value at 1 year was 99.2%.
      The average marginal bone resorption was 0.37 mm (SD 0.39) during the first year
      in function. According to the success criteria of Albrektsson and Zarb, success
      grade 1 was found with 93% of the implants. CONCLUSION: Although limited to the
      short follow-up, immediate loading of NanoTite Prevail implants seems to be a
      viable option in implant rehabilitation, at least when a good initial fixation is
      achieved.

PMID- 20148917
TI  - Mechanisms of angiogenesis: role of hydrogen sulphide.
AB  - 1. Hydrogen sulphide (H(2)S) has recently been recognized as a gasotransmitter
      that regulates angiogenesis in vitro and in vivo under physiological and
      ischaemic conditions. 2. In the present review, the mechanisms underlying
      angiogenesis are summarized briefly and the most recent progress in H(2)S-induced
      angiogenesis in vivo and in vitro is described. The anti-angiogenic effects of
      garlic extracts, which may serve as substrates for H(2)S-generating enzymes in
      vivo, are also discussed. 3. Hydrogen sulphide increases cell growth, migration
      and the formation of tube-like structures in cultured endothelial cells. These
      effects are dependent on activation of the phosphatidylinositol 3-kinase-Akt
      survivin signalling pathway. Neovascularization in vivo has also been
      demonstrated to be promoted in the mouse Matrigel plug assay, as well as in
      chicken chorioallantoic membranes. In a rat unilateral hindlimb ischaemic model,
      treatment with sodium hydrosulphide (NaHS), an H(2)S donor, promotes significant
      angiogenesis and improves regional blood flow. These effects may be mediated by
      interactions between upregulated vascular endothelial growth factor (VEGF) in
      skeletal muscle cells and VEGF receptor 2 and the downstream signalling element
      Akt in vascular endothelial cells. However, H(2)S does not exhibit a pro
      angiogenic effect at a high concentrations/doses. 4. Based on the studies
      reviewed in the present article, we assume that, at physiologically relevant
      doses/concentrations, H(2)S/HS(-) promote angiogenesis at least partly via the
      VEGF signalling pathway. At high doses, H(2)S/HS(-) may act on additional
      cellular targets to evoke mechanisms that counteract the pro-angiogenic pathways.
      More studies need to be performed analysing the general interactions between
      H(2)S/HS(-) and other molecules, including other gasotransmitters, such as nitric
      oxide and carbon monoxide (CO).

PMID- 20148918
TI  - The exclusion of dead bacterial cells is essential for accurate molecular
      analysis of clinical samples.
AB  - The DNA-based techniques used to detect bacteria in clinical samples are unable
      to discriminate between live bacteria, dead bacteria, and extracellular DNA. This
      failure to limit analysis to viable bacterial cells represents a significant
      problem, leading to false-positive results, as well as a failure to resolve the
      impact of antimicrobial therapy. The use of propidium monoazide treatment
      significantly reduces the contribution of dead cells and extracellular DNA to
      such culture-independent analyses. Here, the increased ability to resolve the
      impact of antibiotic therapy on Pseudomonas aeruginosa load in cystic fibrosis
      respiratory samples reveals statistically significant changes that would
      otherwise go undetected.

PMID- 20148919
TI  - A seroprevalence study of poliovirus antibody against a collection of recombinant
      and non-recombinant poliovirus vaccine strains in the population of southern
      Greece.
AB  - In this study, the serological status of the southern Greek population in the 1
      10-year, 11-20-year, 21-30-year and 31-40-year age groups with regard to Sabin
      vaccine strains and a collection of 15 recombinant and four non-recombinant
      poliovirus vaccine strains was determined. For all three poliovirus types, the
      highest neutralization test (NT) titres were observed in the 1-10- year age
      group, indicating a good response to vaccination. In general, the serological
      status of the population of southern Greece with regard to poliovirus is better
      for types 1 and 2 than for type 3. The presence of the lowest NT titre in the 21-
      30-year age group against poliovirus type 3 suggests the need for a booster dose
      of monovalent Sabin3 vaccine to ensure personal and herd immunity.

PMID- 20148920
TI  - Two cases of disseminated Mycobacterium avium infection associated with a new
      immunodeficiency syndrome related to CXCR4 dysfunctions.
AB  - Disseminated Mycobacterium avium complex (MAC) infection is a rare but severe
      disease mostly seen in patients with AIDS. It has been previously described in
      patients suffering from other kinds of immunodeficiency (e.g. primary
      immunodeficiency diseases in children or hairy cell leukaemia). We report two
      cases of disseminated MAC disease in young women with extended granulomatosis
      that revealed a new form of severe immunodeficiency syndrome. Both clinical
      observations initially appeared to be very similar to WHIM syndrome (Warts,
      Hypogammaglobulinemia, Infection, Myelokathexis), a rare immunodeficiency disease
      correlated with CXC chemokine receptor 4 (CXCR4) mutation leading to an impaired
      internalization of the receptor upon its ligand CXCL12. We investigated the CXCR4
      status of the lymphocytes in both patients and found a severe defect in CXCL12
      promoted internalization but no mutation of its gene. Moreover, myelokathexis was
      not noted in bone marrow biopsies and therefore a diagnosis of WHIM syndrome
      could not be assessed. This immunodeficiency syndrome associated with CXCR4
      dysfunction was responsible for severe MAC infection in our patients, with a
      fatal outcome in one case. It may be possible that these patients would have
      benefited from early antimycobacterial infection or azythromycin prophylaxis.

PMID- 20148921
TI  - Clinical significance of signal pattern of high-risk human papillomavirus using a
      novel fluorescence in situ hybridization assay in cervical cytology.
AB  - The present study aimed to evaluate a novel fluorescence in situ hybridization
      (FISH) assay for detecting the high-risk human papillomavirus (HR-HPV) DNA and
      signal pattern in cervical cytology specimens and for identifying cervical
      intraepithelial neoplasia (CIN) lesions. One hundred and ninety-six liquid-based
      cytology specimens with CIN were recruited. The signal pattern (punctate, mixed
      punctate and diffuse, and diffuse) detected by FISH was compared with E6 mRNA and
      correlated with histological classification. FISH and E6-type specific polymerase
      chain reaction (PCR) had fair to good agreement for detecting HPV DNA across all
      grades of CIN (kappa coefficient, 0.37-0.73). Among 44 samples of negative FISH
      and positive E6 type-specific PCR in HPV 16, 18, 31, 33, 52 and 58, 82% (36/44)
      of E6 mRNA were not detected, in contrast to 41% (48/118) of positive FISH and
      positive E6 type-specific PCR (p <0.0001). Among HR-HPV DNA positive cases tested
      by the FISH assay, the specificity of predicting CIN3 using the punctuate pattern
      is higher than that using E6 mRNA (96.3% vs. 44.8%). The punctate pattern was 0%
      in patients with <CIN1 lesions, 8.7% for CIN1 lesions, 6.1% for CIN2 lesions, and
      34.0% for CIN3 lesions (p 0.001). The odds ratios were 8.7-fold higher (2.7-27.8,
      p <0.0001) for the punctate pattern versus the mixed punctate and diffuse
      pattern, and the diffuse pattern, for predicting CIN3 lesions. The novel FISH
      assay is comparable to PCR for detecting HPV DNA in cervical cytology with CIN
      lesions. The punctate signal pattern detected by the FISH assay can be more
      biologically and clinically relevant for clinically detecting CIN3 lesions.

PMID- 20148922
TI  - Postoperative changes in fatigue, physical function and body composition: an
      analysis of the amalgamated data from five randomized trials on patients
      undergoing colorectal surgery.
AB  - AIM: Changes in postoperative fatigue, physical function and body composition
      were described in patients after open colorectal surgery, and factors that
      predicted postoperative fatigue 1 month after surgery were identified. METHOD:
      Data from five clinical intervention studies from 1991 to 2005 were amalgamated.
      Patients (n = 385) were examined preoperatively, at discharge and 1 month
      postoperatively. The level of fatigue was scored subjectively from 1 'fit' to 10
      'fatigued' on a modified visual analogue scale and by objective measurements of
      hand grip and knee extension strength, work capacity, weight, lean body mass and
      fat mass. A logistic regression analysis was used to identify the predictors of a
      high fatigue score 1 month postoperatively. RESULTS: Preoperatively, only 17% had
      a high fatigue score (>= 5.5), whereas 65 and 30% had a high fatigue score at
      discharge and 1 month postoperatively, respectively. Postoperatively, there was a
      significant fall in physical performance, weight, lean body mass and fat mass
      that did not normalize by 1 month. High preoperative and discharge fatigue
      scores, major complications and the loss of lean body mass significantly
      increased the risk of fatigue 1 month postoperatively. CONCLUSION: Open
      colorectal surgery was associated with a significant increase in postoperative
      fatigue and a decline in physical performance, weight and lean body mass. Major
      complications, a high perioperative fatigue score and the loss of lean body mass
      increased the risk of long-term fatigue.

PMID- 20148923
TI  - Generation of genetically modified animals using spermatogonial stem cells.
AB  - Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis, and
      are unique tissue-specific stem cells because of their ability to transmit
      genetic information to offspring. Generation of knockout mice using mouse SSCs
      became feasible after the successful establishment of protocols for the
      transplantation and long-term culture of these cells, called germline stem (GS)
      cells. Furthermore, SSCs can acquire pluripotentiality similar to that of
      embryonic stem (ES) cells, in addition to their highly differentiated
      spermatogenic potential. These ES-like cells, called multipotent GS (mGS) cells,
      are capable of generating knockout mice in a manner similar to that of ES cells.
      The use of GS and mGS cells for animal transgenesis has added a new dimension to
      gene-targeting technology using ES cells and somatic cell nuclear transfer, which
      has limited application. Furthermore, for regenerative medicine purposes, the use
      of mGS will settle problems such as ethics issues and immunological rejection
      associated with ES cells, as well as risks of insertional mutagenesis associated
      with integrated genes into induced pluripotent stem cells.

PMID- 20148924
TI  - Mouse ES cell culture system as a model of development.
AB  - Mouse embryonic stem (mES) cells are pluripotent stem cells derived from pre
      implantation embryos. They are regarded as an essential tool for studying mouse
      development, as they provide a means for generating knock-out mouse lines. This,
      however, is not the sole utility of the mES cell system. They undergo
      differentiation in culture, mimicking the morphological differentiation of peri
      implantation embryos from epiblast to egg-cylinder stage. Moreover, they retain
      the capacity to respond to triggers of differentiation toward trophectoderm and
      primitive endoderm by forced activation. For these reasons, mES cells can be
      regarded as a useful tool for analyzing molecular mechanisms underlying early
      mouse development.

PMID- 20148925
TI  - Dermal fibroblasts contribute to multiple tissues in the accessory limb model.
AB  - The accessory limb model has become an alternative model for performing
      investigations of limb regeneration in an amputated limb. In the accessory limb
      model, a complete patterned limb can be induced as a result of an interaction
      between the wound epithelium, a nerve and dermal fibroblasts in the skin. Studies
      should therefore focus on examining these tissues. To date, however, a study of
      cellular contributions in the accessory limb model has not been reported. By
      using green fluorescent protein (GFP) transgenic axolotl tissues, we can trace
      cell fate at the tissue level. Therefore, in the present study, we transgrafted
      GFP skin onto the limb of a non-GFP host and induced an accessory limb to
      investigate cellular contributions. Previous studies of cell contribution to
      amputation-induced blastemas have demonstrated that dermal cells are the
      progenitors of many of the early blastema cells, and that these cells contribute
      to regeneration of the connective tissues, including cartilage. In the present
      study, we have determined that this same population of progenitor cells responds
      to signaling from the nerve and wound epithelium in the absence of limb
      amputation to form an ectopic blastema and regenerate the connective tissues of
      an ectopic limb. Blastema cells from dermal fibroblasts, however, did not
      differentiate into either muscle or neural cells, and we conclude that dermal
      fibroblasts are dedifferentiated along its developmental lineage.

PMID- 20148926
TI  - Alternative splicing of SMADs in differentiation and tissue homeostasis.
AB  - Tissue-specific alternate splicing is an important means of regulating gene
      expression during development. The effector proteins for the transforming growth
      factor-beta signaling pathway, the SMADs, encode distinct isoforms generated via
      alternate splicing, which appear to have distinct tissue-specific expression
      profiles and functions. Here, we discuss the roles of various SMAD isoforms, and
      the consequences of mis-regulation of SMAD splicing in development and tissue
      homeostasis.

PMID- 20148927
TI  - Heterogeneous landscapes promote population stability.
AB  - Habitat heterogeneity is often suggested as being important for the stability of
      populations, and promoted as a means to aid the conservation of species, but the
      evidence for such an assumption is poor. Here we show that heterogeneous
      landscapes that contain a variety of suitable habitat types are associated with
      more stable population dynamics for 35 British butterfly species from 166 sites.
      In addition, topographic heterogeneity may also promote stability. Our results
      were robust to different measures of population variability, differences in mean
      abundance among sites, and to the spatial scale (radius 1-5 km around the centres
      of sites) at which landscapes were analysed. Responses to landscape heterogeneity
      differed among species; for more mobile 'wider-countryside' species, habitat
      heterogeneity at larger landscape scales had the strongest effect on population
      dynamics. We suggest that heterogeneous landscapes offer a greater range of
      resources and microclimates, which can buffer populations against climatic
      variation and generate more stable population dynamics.

PMID- 20148928
TI  - Regime shifts in ecological systems can occur with no warning.
AB  - Predicting regime shifts - drastic changes in dynamic behaviour - is a key
      challenge in ecology and other fields. Here we show that the class of ecological
      systems that will exhibit leading indicators of regime shifts is limited, and
      that there is a set of ecological models and, therefore, also likely to be a
      class of natural systems for which there will be no forewarning of a regime
      change. We first describe how nonlinearities in combination with environmental
      variability lead to model descriptions that will not have smooth potentials,
      concluding that many ecological systems are described by systems without smooth
      potentials and thus will not show typical leading indicators of regime shifts. We
      then illustrate the impact of these general arguments by numerically examining
      the dynamics of several model ecological systems under slowly changing
      conditions. Our results offer a cautionary note about the generality of
      forecasting sudden changes in ecosystems.

PMID- 20148929
TI  - The autoinducer synthase LqsA and putative sensor kinase LqsS regulate phagocyte
      interactions, extracellular filaments and a genomic island of Legionella
      pneumophila.
AB  - The amoebae-resistant opportunistic pathogen Legionella pneumophila employs a
      biphasic life cycle to replicate in host cells and spread to new niches. Upon
      entering the stationary growth phase, the bacteria switch to a transmissive
      (virulent) state, which involves a complex regulatory network including the lqs
      gene cluster (lqsA-lqsR-hdeD-lqsS). LqsR is a putative response regulator that
      promotes host-pathogen interactions and represses replication. The autoinducer
      synthase LqsA catalyses the production of the diffusible signalling molecule 3
      hydroxypentadecan-4-one (LAI-1) that is presumably recognized by the sensor
      kinase LqsS. Here, we analysed L. pneumophila strains lacking lqsA or lqsS.
      Compared with wild-type L. pneumophila, the DeltalqsS strain was more salt
      resistant and impaired for the Icm/Dot type IV secretion system-dependent uptake
      by phagocytes. Legionella pneumophila strains lacking lqsS, lqsR or the
      alternative sigma factor rpoS sedimented more slowly and produced extracellular
      filaments. Deletion of lqsA moderately reduced the uptake of L. pneumophila by
      phagocytes, and the defect was complemented by expressing lqsA in trans.
      Unexpectedly, the overexpression of lqsA also restored the virulence defect and
      reduced filament production of L. pneumophila mutant strains lacking lqsS or
      lqsR, but not the phenotypes of strains lacking rpoS or icmT. These results
      suggest that LqsA products also signal through sensors not encoded by the lqs
      gene cluster. A transcriptome analysis of the DeltalqsA and DeltalqsS mutant
      strains revealed that under the conditions tested, lqsA regulated only few genes,
      whereas lqsS upregulated the expression of 93 genes at least twofold. These
      include 52 genes clustered in a 133 kb high plasticity genomic island, which is
      flanked by putative DNA-mobilizing genes and encodes multiple metal ion efflux
      pumps. Upon overexpression of lqsA, a cluster of 19 genes in the genomic island
      was also upregulated, suggesting that LqsA and LqsS participate in the same
      regulatory circuit.

PMID- 20148930
TI  - Metatranscriptomic array analysis of 'Candidatus Accumulibacter phosphatis'
      enriched enhanced biological phosphorus removal sludge.
AB  - Here we report the first metatranscriptomic analysis of gene expression and
      regulation of 'Candidatus Accumulibacter'-enriched lab-scale sludge during
      enhanced biological phosphorus removal (EBPR). Medium density oligonucleotide
      microarrays were generated with probes targeting most predicted genes
      hypothesized to be important for the EBPR phenotype. RNA samples were collected
      at the early stage of anaerobic and aerobic phases (15 min after acetate addition
      and switching to aeration respectively). We detected the expression of a number
      of genes involved in the carbon and phosphate metabolisms, as proposed by EBPR
      models (e.g. polyhydroxyalkanoate synthesis, a split TCA cycle through
      methylmalonyl-CoA pathway, and polyphosphate formation), as well as novel genes
      discovered through metagenomic analysis. The comparison between the early stage
      anaerobic and aerobic gene expression profiles showed that expression levels of
      most genes were not significantly different between the two stages. The majority
      of upregulated genes in the aerobic sample are predicted to encode functions such
      as transcription, translation and protein translocation, reflecting the rapid
      growth phase of Accumulibacter shortly after being switched to aerobic
      conditions. Components of the TCA cycle and machinery involved in ATP synthesis
      were also upregulated during the early aerobic phase. These findings support the
      predictions of EBPR metabolic models that the oxidation of intracellularly stored
      carbon polymers through the TCA cycle provides ATP for cell growth when oxygen
      becomes available. Nitrous oxide reductase was among the very few Accumulibacter
      genes upregulated in the anaerobic sample, suggesting that its expression is
      likely induced by the deprivation of oxygen.

PMID- 20148931
TI  - Development and validation of a qPCR-based method for quantifying Shiga toxin
      encoding and other lambdoid bacteriophages.
AB  - To address whether seasonal variability exists among Shiga toxin-encoding
      bacteriophage (Stx phage) numbers on a cattle farm, conventional plaque assay was
      performed on water samples collected over a 17 month period. Distinct seasonal
      variation in bacteriophage numbers was evident, peaking between June and August.
      Removal of cattle from the pasture precipitated a reduction in bacteriophage
      numbers, and during the winter months, no bacteriophage infecting Escherichia
      coli were detected, a surprising occurrence considering that 10(31) tailed
      bacteriophages are estimated to populate the globe. To address this discrepancy a
      culture-independent method based on quantitative PCR was developed. Primers
      targeting the Q gene and stx genes were designed that accurately and
      discriminately quantified artificial mixed lambdoid bacteriophage populations.
      Application of these primer sets to water samples possessing no detectable phages
      by plaque assay, demonstrated that the number of lambdoid bacteriophage ranged
      from 4.7 x 10(4) to 6.5 x 10(6) ml(-1), with one in 10(3) free lambdoid
      bacteriophages carrying a Shiga toxin operon (stx). Specific molecular biological
      tools and discriminatory gene targets have enabled virus populations in the
      natural environment to be enumerated and similar strategies could replace
      existing propagation-dependent techniques, which grossly underestimate the
      abundance of viral entities.

PMID- 20148932
TI  - Gene diversity of CYP153A and AlkB alkane hydroxylases in oil-degrading bacteria
      isolated from the Atlantic Ocean.
AB  - Alkane hydroxylases, including the integral-membrane non-haem iron monooxygenase
      (AlkB) and cytochrome P450 CYP153 family, are key enzymes in bacterial alkane
      oxidation. Although both genes have been detected in a number of bacteria and
      environments, knowledge about the diversity of these genes in marine alkane
      degrading bacteria is still limited, especially in pelagic areas. In this report,
      177 bacterial isolates, comprising 43 genera, were obtained from 18 oil-degrading
      consortia enriched from surface seawater samples collected from the Atlantic
      Ocean. Many isolates were confirmed to be the first oil-degraders in their
      affiliated genera including Brachybacterium, Idiomarina, Leifsonia, Martelella,
      Kordiimonas, Parvibaculum and Tistrella. Using degenerate PCR primers, alkB and
      CYP153A P450 genes were surveyed in these bacteria. In total, 82 P450 and 52 alkB
      gene fragments were obtained from 80 of the isolates. These isolates mainly
      belonged to Alcanivorax, Bacillus, Erythrobacter, Martelella, Parvibaculum and
      Salinisphaera, some of which were reported, for the first time, to encode alkane
      hydroxylases. Phylogenetic analysis showed that both genes were quite diverse and
      formed several clusters, most of which were generated from various Alcanivorax
      bacteria. Noticeably, some sequences, such as those from the Salinisphaera genus,
      were grouped into a distantly related novel cluster. Inspection of the linkage
      between gene and host revealed that alkB and P450 tend to coexist in Alcanivorax
      and Salinisphaera, while in all isolates of Parvibaculum, only P450 genes were
      found, but of multiple homologues. Multiple homologues of alkB mostly cooccurred
      in Alcanivorax isolates. Conversely, distantly related isolates contained similar
      or even identical sequences. In summary, various oil-degrading bacteria, which
      harboured diverse P450 and alkB genes, were found in the surface water of
      Atlantic Ocean. Our results help to show the diversity of P450 and alkB genes in
      prokaryotes, and to portray the geographic distribution of oil-degrading bacteria
      in marine environments.

PMID- 20148933
TI  - Healthcare costs of multiple myeloma: an Italian study.
AB  - Few economic evaluations are currently available on multiple myeloma (MM) and
      they address treatment-related rather than disease-related costs. We estimated
      resource utilisation and costs associated with MM in an Italian haematology
      department. This was a single-centre observational study which followed
      retrospectively for 2 years 90 patients with MM stages II-III. To investigate the
      association between costs and age as a prognostic factor for treatment
      eligibility, patients were classified in two age groups (under 65 or >65). The
      annual average cost per patient was very similar in the two subgroups. Drugs and
      hospitalisations were the largest cost components. Differences between the two
      age groups were significant only for drugs, hospital admissions and day hospital
      (DH) days. Autologous stem-cell transplantation (ASCT) accounted for more than
      80% of the non-pharmacological therapy costs, being nearly double in the younger
      patients. Cost of elderly patients is comparable with that of younger ones who
      generally receive expensive procedures such as ASCT. The higher hospital costs of
      younger patients were counterbalanced by supportive pharmaceutical care and DH
      days for older patients, mainly in the group treated with new immunomodulatory
      agents. Further multi-centre studies on larger samples of patients are needed.

PMID- 20148934
TI  - A study of 28 flat bone osteosarcomas: prognostic factors and early and long-term
      outcome.
AB  - Limited information is available on clinical management of Flat Bone
      Osteosarcomas (FBOS). We retrospectively analysed prognostic factors and outcome.
      Twenty-eight patients were treated in our institution. Survival curves were
      obtained by the Kaplan-Meier method and compared with the log-rank test. The
      overall survival (OS) rates at 5 and 10 years were 52.4% and 45.8% respectively.
      The event-free survival (EFS) rates at 5 and 10 years were 41.5%. The factors
      influencing EFS in univariate analysis were location, metastatic disease at
      diagnosis, effect of neoadjuvant chemotherapy, histological response and adequate
      local tumour control. Location, metastatic disease at diagnosis, effect of
      neoadjuvant chemotherapy, histological response and local recurrence were
      statistically correlated with OS. Multivariate analysis retained metastatic
      disease at diagnosis as prognostic factors of EFS and OS. Our results suggest a
      more favourable outcome of FBOS as the use of a treatment scheme based on the
      protocols for long bone osteosarcomas. However, an adequate local treatment is
      essential to ensure a better outcome.

PMID- 20148935
TI  - Comparing the needs of health professional and peer cancer support group
      facilitators in an Australian context.
AB  - This study explored the perceived needs of health professional and peer
      facilitators of cancer support groups. Participants were facilitators of support
      groups affiliated with The Cancer Council Victoria (Australia). Facilitators
      completed questionnaires assessing their experience of support group
      facilitation, including training and support needs. Data from health professional
      and peer facilitators (n= 74) were analysed in this paper. The majority of
      facilitators (88%) were female; 57% had run their group for more than 3 years,
      and 47% reported between 11 and 20 people attended each group. Although results
      showed the characteristics of support groups are broadly similar for peers and
      professionals, there were some distinct differences in perceived needs. Health
      professional facilitators were more likely than peers to regard training as
      valuable and beneficial to their role. In addition, health professionals more
      frequently reported needing debriefing as well as more difficulty accessing
      debriefing than cancer peers. This study builds on the small body of literature
      exploring the experiences of cancer support group facilitators. Given the
      experiences and needs of health professional and peer facilitators may differ, it
      may be relevant to tailor training and support so that it meets the needs of both
      health professionals and cancer peers.

PMID- 20148937
TI  - 'It don't make sense to worry too much': the experience of prostate cancer in
      African-Caribbean men in the UK.
AB  - The incidence of prostate cancer among African-Caribbean men in the UK is three
      times that among men from the majority population. Little attention, however, has
      been given to the perceptions and experiences of treatment and care of men from
      these communities with prostate cancer. This qualitative study is the first such
      investigation, situating men's accounts within the context of their personal
      history and social environment. Using a community-based, snowball sampling
      method, 16 first generation African-Caribbean men living in Central England were
      recruited. Similarities and divergence in men's experience were identified
      through thematic analysis of interview transcripts. Men's responses to their
      situation were influenced by aspects of migration and historical context as well
      as culture. While medical treatment was highly valued, common difficulties were
      compounded by problems of health professional-patient communication, stereotyping
      and insensitivity of some staff. Lack of coordination between services and
      agencies adversely affected the well-being of frail men and widowers. Findings
      suggest the need for a more proactive approach to giving and eliciting
      information combined with cultural diversity training. More systematic referral
      procedures and information exchange between African-Caribbean men with prostate
      cancer and their general practitioner, hospital, social care and voluntary
      agencies, churches and community organisations are indicated.

PMID- 20148936
TI  - Patient preferences for the delivery of bad news - the experience of a UK Cancer
      Centre.
AB  - The primary aim of this study was to assess how patients would prefer to be given
      their cancer diagnosis in a typical UK cancer centre. Two hundred and forty-four
      patients attending the oncology outpatient department at the Leicester Royal
      Infirmary, UK, were recruited. Patients were invited to complete the Measure of
      Patients' Preferences questionnaire, write comments on their own experience of
      the breaking bad news consultation and choose their preferred role in decision
      making. Over 90% of questionnaires were completed. Patients rated the items
      addressing the message content of the consultation as more important than the
      facilitative or the supportive aspects. Over 80% of patients wrote a detailed
      account of their experiences, of which 60% were satisfied with the consultation.
      Most of the patients who were dissatisfied commented on the unsympathetic or
      pessimistic manner of the doctor. The majority of patients wanted a collaborative
      role in decision making. Regarding the cancer diagnosis, the majority of patients
      have information needs, want to be involved in treatment decisions and know their
      prognosis. The difficulty for physicians is how to meet individual information
      needs, give hope, but not deliver unrealistic expectations.

PMID- 20148938
TI  - proFamilies: a psycho-educational multi-family group intervention for cancer
      patients and their families.
AB  - This paper describes a psycho-educational multi-family discussion group
      intervention for cancer patients and their families (proFamilies) which was
      implemented and evaluated at the IPOFG - CROC (Portuguese Cancer Institute,
      Regional Centre of Coimbra). It is a brief and highly structured programme which
      involves educational and support components and is based on multi-family
      discussion groups, including patients and non-patient family members. Five groups
      were established, involving 19 families, and a total of 57 people. The paper
      focuses on the practical aspects of the intervention, its development and its
      evaluation. Our results suggest that the programme responds to the patients' and
      their families' needs and that participation in proFamilies prevents an increase
      in the patient's level of psycho-social maladjustment, promotes an adequate level
      of family cohesion and diminishes the perceived stress of patients and family
      members.

PMID- 20148939
TI  - Occupational health and safety of personnel handling chemotherapeutic agents in
      Greek hospitals.
AB  - The expansion of chemotherapy raised concerns about the health and safety of
      hospital personnel. Very little is known about the conditions of handling of
      chemotherapeutic agents by healthcare workers in Greece and possible adverse
      effects related to their safety practices, as well as the safety policies adopted
      by the Greek hospitals. A self-evaluation questionnaire was completed by 353
      healthcare workers involved with the use of chemotherapeutic drugs in 24 Greek
      hospitals and the answers were statistically analysed. The majority of the
      healthcare workers are aware of the dangers of their work, although they had
      received limited training and medical surveillance. A significant percentage of
      them does not use personal protective equipment or use it inadequately. The
      safety design of their workplace is rather poor. Different health problems have
      been experienced, deriving from the respiratory, central nervous system,
      reproductive, gastrointestinal and musculoskeletal system. The improvement of
      safety training and procedures as well as medical surveillance seems to be a
      vital priority of hospital administration in Greece, in order to comply with the
      European guidelines and for the prevention of occupational diseases and
      environmental pollution.

PMID- 20148940
TI  - An exploratory trial of preventative rehabilitation on shoulder disability and
      quality of life in patients following neck dissection surgery.
AB  - Patients commonly develop shoulder disability and reduction in quality of life
      (QOL) following neck dissection surgery. There is a lack of studies investigating
      the impact of preventative rehabilitation to prevent shoulder disability in this
      population. An exploratory trial was undertaken to investigate this gap in the
      head and neck cancer literature. Thirty-two subjects were randomly assigned to
      either one of two groups: early physiotherapy for a period of 3 months following
      surgery and current routine inpatient care and advice. Blinded measurement of
      shoulder function and QOL were recorded pre-operatively and at 1 year following
      surgery. No difference was found using between-group analysis (Mann-Whitney U
      Test) for any outcome measures observed. Descriptive data analysis suggests that
      subjects receiving early physiotherapy had a perception of increased physical
      well-being when compared with subjects receiving routine care. There may be some
      clinical significance that subjects receiving a course of physiotherapy did
      appear to rate their physical well-being higher than those subjects not
      undergoing rehabilitation. Further research to investigate the preventative
      effects of physiotherapy on this population should consider the use of head and
      neck cancer-specific outcome measurement of both shoulder disability and QOL.

PMID- 20148941
TI  - EZH2 silencing by RNA interference inhibits proliferation in bladder cancer cell
      lines.
AB  - The Enhancer of Zeste homologue2 gene (EZH2) is frequently expressed at high
      levels in malignant tumours, including bladder cancer. It functions as a
      transcriptional regulator to the maintenance of cell identity, cell cycle
      regulation and oncogenesis. In the study, we detected EZH2 expression in bladder
      cancer tissues. These results showed EZH2 high expression in bladder cancer
      tissue at level of transcript and protein compared with normal bladder tissue and
      EZH2 expression correlated positively with tumour stage and grade. Then, we used
      RNA interference to inhibit EZH2 expression in bladder cancer EJ cell line.
      Efficient downregulation of EZH2 resulted in significantly decreased cell
      proliferation in EJ cells and retarded transition of G(1) phase to S phase. Our
      data suggest that EZH2 is involved in the tumourigenesis of bladder cancer and
      EZH2 downregulation contributes to inhibiting malignant growth by retarding cell
      entrance to S phase.

PMID- 20148942
TI  - Organising pneumonia mimicking invasive fungal disease in patients with
      leukaemia.
AB  - Clinical charts from 63 consecutive highly immunocompromised haematologic
      patients presenting with pulmonary nodular lesions on CT scan, classified as
      either probable or possible invasive fungal disease (IFD) according to the
      revised EORTC/MSG classification, were retrospectively studied. Histopathological
      analysis of lung tissues, available for 23 patients, demonstrated proven IFD in
      17 cases (14 invasive aspergillosis and 3 invasive zygomycosis), diffuse alveolar
      damage in one and organising pneumonia (OP) in five cases. In the OP cases, three
      of which have been defined as probable IFD according to EORTC/MSG classification,
      extensive immunohistochemical, molecular and immunological analyses for fungi
      were negative. Our case descriptions extend the notion that OP may be encountered
      as a distinct histopathological entity in pulmonary nodular lesions in patients
      with leukaemia with probable/possible IFD.

PMID- 20148943
TI  - Primary gastric diffuse large B-cell Lymphoma (DLBCL): analyses of prognostic
      factors and value of pretreatment FDG-PET scan.
AB  - OBJECTIVES: We report a single institution experience with gastric diffuse large
      B-cell lymphoma (DLBCL) in an attempt to evaluate the roles of different
      treatment modalities, to assess the value of pretreatment positron emission
      tomography (PET) scan, and to identify potential prognostic factors. METHODS:
      Among 384 patients diagnosed with DLBCL between 1995 and 2008, 75 patients had
      primary gastric DLBCL and were reviewed and analyzed. RESULTS: The median age was
      66. International prognostic index (IPI) risk was low in 52%, low-intermediate in
      23%, high-intermediate in 9%, and high in 16%. Pretreatment PET scan was highly
      sensitive in detecting gastric lesions except stage I gastric DLBCL without
      detectable mass by CT or gastroscopy. As a general rule, patients with limited
      stage disease were treated with three times of CHOP (with or without rituximab)
      and radiotherapy, and those with advanced-stage disease were treated with eight
      cycles of CHOP (with or without rituximab), and radiotherapy was given to
      residual diseases after chemotherapy. Three-year overall survival (OS) rate was
      78%. Multivariate analysis revealed that low albumin, hemoglobin <12.0 g/dL, and
      treatment without rituximab were independently associated with shorter OS. Low
      albumin, hemoglobin <12.0 g/dL,and advanced stage were independently associated
      with shorter progression-free survival. CONCLUSION: We showed the survival
      benefit of rituximab and potential prognostic value of pretreatment hemoglobin
      and serum albumin levels in gastric DLBCL.

PMID- 20148944
TI  - Differential muscle-driven synaptic remodeling in the neuromuscular junction
      after denervation.
AB  - We used knock-in mice that express green fluorescent protein (GFP)-labeled
      embryonic-type acetylcholine receptors to investigate postsynaptic responses to
      denervation of fast-twitch and slow-twitch muscle fibers, and to visualize the
      integration of newly synthesized GFP-labeled embryonic-type receptors into adult
      synapses. The embryonic-type receptors are transiently expressed and incorporated
      into the denervated endplates. They replaced synaptic adult-type receptors in a
      directed fashion, starting from the endplate's periphery and proceeding to its
      central regions. The progress of embryonic-type receptor expression with respect
      to transcriptional control is a transient, short-term activation mechanism. The
      less pronounced increase in the expression levels of the GFP-labeled receptors
      revealed a differential shift in the integration and degradation processes that
      constitute the dynamic equilibrium of the synaptic receptor pool. Therefore, we
      were able to model the changes in the total receptor load of the neuromuscular
      endplate following denervation as a function of the abundance of available
      receptors and the initial receptor load of the endplate.

PMID- 20148945
TI  - Peptides from purified soybean beta-conglycinin inhibit fatty acid synthase by
      interaction with the thioesterase catalytic domain.
AB  - Fatty acid synthase (FAS) is uniquely expressed at high levels in cancer cells
      and adipose tissue. The objectives of this study were to identify, purify and
      validate soy FAS inhibitory peptides and to predict their binding modes. Soy
      peptides were isolated from hydrolysates of purified beta-conglycinin by co
      immunoprecipitation and identified using LC-MS/MS. Three peptides, KNPQLR,
      EITPEKNPQLR and RKQEEDEDEEQQRE, inhibited FAS. The biological activity of these
      peptides was confirmed by their inhibitory activity against purified chicken FAS
      (IC(50) = 79, 27 and 16 mum, respectively) and a high correlation (r = -0.7) with
      lipid accumulation in 3T3-L1 adipocytes. The FAS inhibitory potency of soy
      peptides also correlated with their molecular mass, pI value and the number of
      negatively charged and hydrophilic residues. Molecular modeling predicted that
      the large FAS inhibitory peptides (EITPEKNPQLR and RKQEEDEDEEQQRE) bond to the
      thioesterase domain of human FAS with lower interaction energies (-442 and -353
      kcal.mol(-1), respectively) than classical thioesterase inhibitors (Orlistat, -91
      kcal.mol(-1) and C75, -51 kcal.mol(-1)). Docking studies suggested that soy
      peptides blocked the active site through interactions within the catalytic triad,
      the interface cavity and the hydrophobic groove in the human FAS thioesterase
      domain. FAS thioesterase inhibitory activities displayed by the synthetic soy
      peptides EITPEKNPQLR and RKQEEDEDEEQQRE (IC(50) = 10.1 +/- 1.6 and 10.7 +/- 4.4
      mum, respectively) were higher than C75 (58.7 mum) but lower than Orlistat (0.9
      mum). This is the first study to identify FAS inhibitory peptides from purified
      beta-conglycinin hydrolysates and predict their binding modes at the molecular
      level, leading to their possible use as nutraceuticals.

PMID- 20148946
TI  - The SWI/SNF protein BAF60b is ubiquitinated through a signalling process
      involving Rac GTPase and the RING finger protein Unkempt.
AB  - The SWI/SNF chromatin remodelling complexes are important regulators of
      transcription; they consist of large multisubunit assemblies containing either
      Brm or Brg1 as the catalytic ATPase subunit and a variable subset of
      approximately 10 Brg/Brm-associated factors (BAF). Among these factors, BAF60
      proteins (BAF60a, BAF60b or BAF60c), which are found in most complexes, are
      thought to bridge interactions between transcription factors and SWI/SNF
      complexes. We report here on a Rac-dependent process leading to BAF60b
      ubiquitination. Using two-hybrid cloning procedures, we identified a mammalian
      RING finger protein homologous to drosophila Unkempt as a new partner of the
      activated form of RacGTPases and demonstrated that mammalian Unkempt specifically
      binds to BAF60b and promotes its ubiquitination in a Rac1-dependent manner.
      Immunofluorescence studies demonstrated that Unkempt is primarily localized in
      the cytoplasmic compartment, but has the ability to shuttle between the nucleus
      and the cytoplasm, suggesting that the Rac- and Unkempt-dependent process leading
      to BAF60b ubiquitination takes place in the nuclear compartment. Ubiquitinated
      forms of BAF60b were found to accumulate upon treatment with the proteasome
      inhibitor MG132, indicating that BAF60b ubiquitination is of the degradative type
      and could regulate the level of BAF60b in SWI/SNF complexes. Our observations
      support the new idea of a direct connection between Rac signalling and chromatin
      remodelling.

PMID- 20148947
TI  - Analysis of DNA-binding sites on Mhr1, a yeast mitochondrial ATP-independent
      homologous pairing protein.
AB  - The Mhr1 protein is necessary for mtDNA homologous recombination in Saccharomyces
      cerevisiae. Homologous pairing (HP) is an essential reaction during homologous
      recombination, and is generally catalyzed by the RecA/Rad51 family of proteins in
      an ATP-dependent manner. Mhr1 catalyzes HP through a mechanism similar, at the
      DNA level, to that of the RecA/Rad51 proteins, but without utilizing ATP.
      However, it has no sequence homology with the RecA/Rad51 family proteins or with
      other ATP-independent HP proteins, and exhibits different requirements for DNA
      topology. We are interested in the structural features of the functional domains
      of Mhr1. In this study, we employed the native fluorescence of Mhr1's Trp
      residues to examine the energy transfer from the Trp residues to etheno-modified
      ssDNA bound to Mhr1. Our results showed that two of the seven Trp residues (Trp71
      and Trp165) are spatially close to the bound DNA. A systematic analysis of mutant
      Mhr1 proteins revealed that Asp69 is involved in Mg(2+)-dependent DNA binding,
      and that multiple Lys and Arg residues located around Trp71 and Trp165 are
      involved in the DNA-binding activity of Mhr1. In addition, in vivo
      complementation analyses showed that a region around Trp165 is important for the
      maintenance of mtDNA. On the basis of these results, we discuss the function of
      the region surrounding Trp165.

PMID- 20148948
TI  - Parallel evolution at multiple levels in the origin of hummingbird pollinated
      flowers in Ipomoea.
AB  - A transition in flower color accompanying a shift in pollinator guilds is a
      prominent and repeated adaptation in angiosperms. In many cases, shifts to
      similar pollinators are associated with similar flower-color transitions. The
      extent to which this parallelism at the phenotypic level results from parallel
      changes at the biochemical, developmental, and genetic levels, however, remains
      an open question. There have been few attempts to determine whether parallelism
      at these lower levels results from mutation bias or fixation bias of different
      classes of mutation. We address these issues by examining the biochemical,
      developmental, and genetic changes that have occurred in red-flowering species of
      the Mina lineage of morning glories (Ipomoea) and compare these to the changes
      reported for I. horsfalliae, which has independently evolved red flowers. Using
      transgenic techniques, we demonstrate that the transition from blue to red
      flowers in Mina species is due primarily to down-regulation of the enzyme
      flavonol-3'-hydroxylase (F3'H) in flowers but not in vegetative tissues, and that
      this down-regulation is at least partly due to cis-regulatory change in the gene
      for F3'H. These changes are similar to those exhibited by I. horsfalliae,
      indicating parallelism at the biochemical and developmental levels, and possibly
      at the genetic level.

PMID- 20148949
TI  - Discovering exceptional diversifications at continental scales: the case of the
      endemic families of neotropical suboscine passerines.
AB  - The study of continental adaptive radiations has lagged behind research on their
      island counterparts in part because the mere identification of adaptive
      radiations is more challenging at continental scales. Here, I demonstrate a new
      method based on simulations for discovering clades that show exceptionally high
      phenotypic diversity. The method does not require a phylogeny but accounts for
      differences in age and species richness among clades and incorporates effects of
      the phylogenetic structure of data. In addition, I developed a new multivariate
      measure of phenotypic diversity, which has the advantage over other measures of
      disparity in that it takes covariation into account. I applied these methods to a
      clade of endemic Neotropical suboscine passerines, within which the family
      Furnariidae has been considered an adaptive radiation. I found that the families
      Thamnophilidae, Furnariidae, and Dendrocolaptidae have experienced a higher rate
      of cladogenesis than have other clades. Although Thamnophilidae is exceptionally
      diverse in body size, only Furnariidae and Dendrocolaptidae are exceptionally
      diverse in shape. The combination of high rates of cladogenesis and high
      morphometric diversity in traits related to feeding and locomotion suggest that
      the clade Furnariidae-Dendrocolaptidae represent an authentic continental
      adaptive radiation.

PMID- 20148950
TI  - Evolution of flowering time in experimental wheat populations: a comprehensive
      approach to detect genetic signatures of natural selection.
AB  - In annual plant species, flowering time is a major adaptive trait that
      synchronizes the initiation of reproduction with favorable environmental
      conditions. Here, we aimed at studying the evolution of flowering time in three
      experimental populations of bread wheat, grown in contrasting environments
      (Northern to Southern France) for 12 generations. By comparing the distribution
      of phenotypic and presumably neutral variation, we first showed that flowering
      time responded to selection during the 12 generations of the experiment. To get
      insight into the genetic architecture of that trait, we then tested whether the
      distribution of genetic polymorphisms at six candidate genes, presumably involved
      in the trait expression, departed from neutral expectation. To that end, we
      focused on the temporal variation during the course of the experiment, and on the
      spatial differentiation at the end of the experiment, using previously published
      methods adapted to our experimental design. Only those genes that were strongly
      associated with flowering time variation were detected as responding to
      selection. For genes that had low-to-moderate phenotypic effects, or when there
      was interaction across different genes, we did not find evidence of selection
      using methods based on the distribution of temporal or spatial variation. In such
      cases, it might be more informative to consider multilocus and multiallelic
      combinations across genes, which could be the targets of selection.

PMID- 20148951
TI  - Local adaptation maintains clinal variation in melanin-based coloration of
      European barn owls (Tyto alba).
AB  - Ecological parameters vary in space, and the resulting heterogeneity of selective
      forces can drive adaptive population divergence. Clinal variation represents a
      classical model to study the interplay of gene flow and selection in the dynamics
      of this local adaptation process. Although geographic variation in phenotypic
      traits in discrete populations could be remainders of past adaptation,
      maintenance of adaptive clinal variation requires recurrent selection. Clinal
      variation in genetically determined traits is generally attributed to adaptation
      of different genotypes to local conditions along an environmental gradient,
      although it can as well arise from neutral processes. Here, we investigated
      whether selection accounts for the strong clinal variation observed in a highly
      heritable pheomelanin-based color trait in the European barn owl by comparing
      spatial differentiation of color and of neutral genes among populations. Barn
      owl's coloration varies continuously from white in southwestern Europe to reddish
      brown in northeastern Europe. A very low differentiation at neutral genetic
      markers suggests that substantial gene flow occurs among populations. The
      persistence of pronounced color differentiation despite this strong gene flow is
      consistent with the hypothesis that selection is the primary force maintaining
      color variation among European populations. Therefore, the color cline is most
      likely the result of local adaptation.

PMID- 20148952
TI  - Evolvability of individual traits in a multivariate context: partitioning the
      additive genetic variance into common and specific components.
AB  - Genetic covariation among multiple traits will bias the direction of evolution.
      Although a trait's phenotypic context is crucial for understanding evolutionary
      constraints, the evolutionary potential of one (focal) trait, rather than the
      whole phenotype, is often of interest. The extent to which a focal trait can
      evolve independently depends on how much of the genetic variance in that trait is
      unique. Here, we present a hypothesis-testing framework for estimating the
      genetic variance in a focal trait that is independent of variance in other
      traits. We illustrate our analytical approach using two Drosophila bunnanda trait
      sets: a contact pheromone system comprised of cuticular hydrocarbons (CHCs), and
      wing shape, characterized by relative warps of vein position coordinates. Only 9%
      of the additive genetic variation in CHCs was trait specific, suggesting
      individual traits are unlikely to evolve independently. In contrast, most (72%)
      of the additive genetic variance in wing shape was trait specific, suggesting
      relative warp representations of wing shape could evolve independently. The
      identification of genetic variance in focal traits that is independent of other
      traits provides a way of studying the evolvability of individual traits within
      the broader context of the multivariate phenotype.

PMID- 20148953
TI  - A role for nonadaptive processes in plant genome size evolution?
AB  - Genome sizes vary widely among species, but comprehensive explanations for the
      emergence of this variation have not been validated. Lynch and Conery (2003)
      hypothesized that genome expansion is maladaptive, and that lineages with small
      effective population size (N(e)) evolve larger genomes than those with large N(e)
      as a consequence of the lowered efficacy of natural selection in small
      populations. In addition, mating systems likely affect genome size evolution via
      effects on both N(e) and the spread of transposable elements (TEs). We present a
      comparative analysis of the effects of N(e) and mating system on genome size
      evolution in seed plants. The dataset includes 205 species with monoploid genome
      size estimates (corrected for recent polyploidy) ranging from 2Cx = 0.3 to 65.9
      pg. The raw data exhibited a strong positive relationship between outcrossing and
      genome size, a negative relationship between N(e) and genome size, but no
      detectable N(e)x outcrossing interaction. In contrast, phylogenetically
      independent contrast analyses found only a weak relationship between outcrossing
      and genome size and no relationship between N(e) and genome size. Thus, seed
      plants do not support the Lynch and Conery mechanism of genome size evolution.
      Further work is needed to disentangle contrasting effects of mating systems on
      the efficacy of selection and TE transmission.

PMID- 20148954
TI  - Heterozygosity-fitness correlations: a time for reappraisal.
AB  - Owing to the remarkable progress of molecular techniques, heterozygosity-fitness
      correlations (HFCs) have become a popular tool to study the impact of inbreeding
      in natural populations. However, their underlying mechanisms are often hotly
      debated. Here we argue that these "debates" rely on verbal arguments with no
      basis in existing theory and inappropriate statistical testing, and that it is
      time to reconcile HFC with its historical and theoretical fundaments. We show
      that available data are quantitatively and qualitatively consistent with
      inbreeding-based theory. HFC can be used to estimate the impact of inbreeding in
      populations, although such estimates are bound to be imprecise, especially when
      inbreeding is weak. Contrary to common belief, linkage disequilibrium is not an
      alternative to inbreeding, but rather comes with some forms of inbreeding, and is
      not restricted to closely linked loci. Finally, the contribution of local
      chromosomal effects to HFC, while predicted by inbreeding theory, is expected to
      be small, and has rarely if ever proven statistically significant using adequate
      tests. We provide guidelines to safely interpret and quantify HFCs, and present
      how HFCs can be used to quantify inbreeding load and unravel the structure of
      natural populations.

PMID- 20148955
TI  - Temporal variation at the MHC class IIb in wild populations of the guppy
      (Poecilia reticulata).
AB  - Understanding genetic diversity in natural populations is a fundamental objective
      of evolutionary biology. The immune genes of the major histocompatibility complex
      (MHC) are excellent candidates to study such diversity because they are highly
      polymorphic in populations. Although balancing selection may be responsible for
      maintaining diversity at these functionally important loci, temporal variation in
      selection pressure has rarely been examined. We examine temporal variation in MHC
      class IIB diversity in nine guppy (Poecilia reticulata) populations over two
      years. We found that five of the populations changed significantly more at the
      MHC than at neutral (microsatellite) loci as measured by F(ST), which suggests
      that the change at the MHC was due to selection and not neutral processes.
      Additionally, pairwise population differentiation measures at the MHC were higher
      in 2007 than in 2006, with the signature of selection changing from homogenizing
      to diversifying selection or neutral evolution. Interestingly, within the
      populations the magnitude of the change at the MHC between years was related to
      the change in the proportion of individuals infected by a common parasite,
      indicating a link between genetic structure and the parasite. Our data thereby
      implicate temporal variation in selective pressure as an important mechanism
      maintaining diversity at the MHC in wild populations.

PMID- 20148956
TI  - Reduced gene flow at pericentromeric loci in a hybrid zone involving chromosomal
      races of the house mouse Mus musculus domesticus.
AB  - The West European house mouse, Mus musculus domesticus, is a particularly
      suitable model to investigate the role of chromosomal rearrangements in
      reproductive isolation. In fact, it exhibits a broad range of chromosomal
      polymorphism due to Robertsonian (Rb) fusions leading to various types of contact
      zones between different chromosomal races. In the present study, we analyzed a
      parapatric contact in central Italy between the Cittaducale chromosomal race (CD:
      2n= 22) and the surrounding populations with standard karyotype (2n= 40) to
      understand if Rb fusions play a causative role in speciation. One hundred forty
      seven mice from 17 localities were genotyped by means of 12 microsatellite loci.
      A telomeric and a pericentromeric locus situated on six chromosome arms (four Rbs
      and one telocentric) were selected to detect differences in the amount of gene
      flow for each locus in different chromosomal positions. The analyses performed on
      the two subsets of loci show differences in the level of gene flow, which is more
      restricted near the centromeres of Rb chromosomes. This effect is less pronounced
      in the homozygotes populations settled at the border of the hybrid zone. We
      discuss the possible cause of the differential porosity of gene flow in Rbs
      considering "hybrid dysfunctions" and "suppressed recombination" models.

PMID- 20148957
TI  - The enforcement of cooperation by policing.
AB  - Policing is regarded as an important mechanism for maintaining cooperation in
      human and animal social groups. A simple model providing a theoretical overview
      of the coevolution of policing and cooperation has been analyzed by Frank (1995,
      1996b, 2003, 2009), and this suggests that policing will evolve to fully suppress
      cheating within social groups when relatedness is low. Here, we relax some of the
      assumptions made by Frank, and investigate the consequences for policing and
      cooperation. First, we address the implicit assumption that the individual cost
      of investment into policing is reduced when selfishness dominates. We find that
      relaxing this assumption leads to policing being favored only at intermediate
      relatedness. Second, we address the assumption that policing fully recovers the
      loss of fitness incurred by the group owing to selfishness. We find that relaxing
      this assumption prohibits the evolution of full policing. Finally, we consider
      the impact of demography on the coevolution of policing and cooperation, in
      particular the role for kin competition to disfavor the evolution of policing,
      using both a heuristic "open" model and a "closed" island model. We find that
      large groups and increased kin competition disfavor policing, and that policing
      is maintained more readily than it invades. Policing may be harder to evolve than
      previously thought.

PMID- 20148958
TI  - Geographic variation in the songs of neotropical singing mice: testing the
      relative importance of drift and local adaptation.
AB  - Patterns of geographic variation in communication systems can provide insight
      into the processes that drive phenotypic evolution. Although work in birds,
      anurans, and insects demonstrates that acoustic signals are sensitive to diverse
      selective and stochastic forces, processes that shape variation in mammalian
      vocalizations are poorly understood. We quantified geographic variation in the
      advertisement songs of sister species of singing mice, montane rodents with a
      unique mode of vocal communication. We tested three hypotheses to explain spatial
      variation in the song of the lower altitude species, Scotinomys teguina:
      selection for species recognition in sympatry with congener, S. xerampelinus,
      acoustic adaptation to different environments, and stochastic divergence. Mice
      were sampled at seven sites in Costa Rica and Panama; genetic distances were
      estimated from mitochondrial control region sequences, between-site differences
      in acoustic environment were estimated from climatic data. Acoustic, genetic and
      geographic distances were all highly correlated in S. teguina, suggesting that
      population differentiation in song is largely shaped by genetic drift. Contrasts
      between interspecific genetic-acoustic distances were significantly greater than
      expectations derived from intraspecific contrasts, indicating accelerated
      evolution of species-specific song. We propose that, although much intraspecific
      acoustic variation is effectively neutral, selection has been important in
      shaping species differences in song.

PMID- 20148959
TI  - Mate choice for nonadditive genetic benefits correlate with MHC dissimilarity in
      the rose bitterling (Rhodeus ocellatus).
AB  - Good genes models of mate choice predict additive genetic benefits of choice
      whereas the compatibility hypothesis predicts nonadditive fitness benefits. Here
      the Chinese rose bitterling, Rhodeus ocellatus, a freshwater fish with a resource
      based mating system, was used to separate additive and nonadditive genetic
      benefits of female mate choice. A sequential blocked mating design was used to
      test female mate preferences, and a cross-classified breeding design coupled with
      in vitro fertilizations for fitness benefits of mate choice. In addition, the
      offspring produced by the pairing of preferred and nonpreferred males were reared
      to maturity and their fitness traits were compared. Finally, the MHC DAB1 gene
      was typed and male MHC genotypes were correlated with female mate choice. Females
      showed significant mate preferences but preferences were not congruent among
      females. There was a significant interaction of male and female genotype on
      offspring survival, rate of development, growth rate, and body size. No
      significant male additive effects on offspring fitness were observed. Female mate
      preferences corresponded with male genetic compatibility, which correlated with
      MHC dissimilarity. It is proposed that in the rose bitterling genetic
      compatibility is the mechanism by which females obtain a fitness benefit through
      mate choice and that male MHC dissimilarity, likely mediated by odor cues,
      indicates genetic compatibility.

PMID- 20148960
TI  - Cysteine residues exposed on protein surfaces are the dominant intramitochondrial
      thiol and may protect against oxidative damage.
AB  - Cysteine plays a number of important roles in protecting the cell from oxidative
      damage through its thiol functional group. These defensive functions are
      generally considered to be carried out by the low molecular weight thiol
      glutathione and by cysteine residues in the active sites of proteins such as
      thioredoxin and peroxiredoxin. In addition, there are thiols exposed on protein
      surfaces that are not directly involved with protein function, although they can
      interact with the intracellular environment. In the present study, in subcellular
      fractions prepared from rat liver or heart, we show that the quantitatively
      dominant free thiols are those of cysteine residues exposed on protein surfaces
      and not those carried by glutathione. Within the mitochondrial matrix, the
      concentration of exposed protein thiols is 60-90 mm, which is approximately 26
      fold higher than the glutathione concentration in that compartment. This suggests
      that exposed protein thiols are of greater importance than glutathione for
      nonenzyme catalysed reactions of thiols with reactive oxygen and nitrogen species
      and with electrophiles within the cell. One such antioxidant role for exposed
      protein thiols may be to prevent protein oxidative damage. In the present study,
      in mitochondrial membranes and in complex I, we show that exposed protein thiols
      protect against tyrosine nitration and protein dysfunction caused by
      peroxynitrite. Therefore, exposed protein thiols are the dominant free thiol
      within the cell and may play a critical role in intracellular antioxidant
      defences against oxidative damage.

PMID- 20148961
TI  - Amyloid oligomers: spectroscopic characterization of amyloidogenic protein
      states.
AB  - It is assumed that protein fibrils manifested in amyloidosis result from an
      aggregation reaction involving small misfolded protein sequences being in an
      'oligomeric' or 'prefibrillar' state. This review covers recent optical
      spectroscopic studies of amyloid protein misfolding, oligomerization and amyloid
      fibril growth. Although amyloid fibrils have been studied using established
      protein-characterization techniques throughout the years, their oligomeric
      precursor states require sensitive detection in real-time. Here, fluorescent
      staining is commonly performed using thioflavin T and other small fluorescent
      molecules such as 4-(dicyanovinyl)- julolidine and 1-amino-8-naphtalene
      sulphonate that have high affinity to hydrophobic patches. Thus, populated
      oligomeric intermediates and related 'prefibrillar structures' have been reported
      for several human amyloidogenic systems, including amyloid-beta protein, prion
      protein, transthyretin, alpha-synuclein, apolipoprotein C-II and insulin. To
      obtain information on the progression of the intermediate states, these were
      monitored in terms of fluorescence parameters, such as anisotropy, and quantum
      efficiency changes upon protein binding. Recently, new antibody stains have
      allowed precise monitoring of the oligomer size and distributions using
      multicolor labelling and single molecule detection. Moreover, a pentameric
      thiophene derivative (p-FTAA) was reported to indicate early precursors during A
      beta(1-40) fibrillation, and was also demonstrated in real-time visualization of
      cerebral protein aggregates in transgenic AD mouse models by multiphoton
      microscopy. Conclusively, molecular probes and optical spectroscopy are now
      entering a phase enabling the in vivo interrogation of the role of oligomers in
      amyloidosis. Such techniques used in parallel with in vitro experiments, of
      increasing detail, will probably couple structure to pathogenesis in the near
      future.

PMID- 20148962
TI  - Amyloid oligomers: dynamics and toxicity in the cytosol and nucleus.
AB  - The accumulation of misfolded proteins in the cytosol and nucleus of neuronal
      cells leads to neurodegenerative disorders. Polyglutamine diseases are caused by
      polyglutamine-expanded proteins, whereas mutations in superoxide dismutase 1 lead
      to amyotrophic lateral sclerosis. These structurally unstable mutant species
      perturb essential interactions between normal proteins and tend to aggregate
      because of the presence of exposed hydrophobic surfaces. Accumulating evidence
      suggests that soluble species, including misfolded monomers and oligomers, are
      more toxic than large insoluble aggregates or inclusions. Spectroscopic analysis,
      including fluorescence recovery after photobleaching and fluorescence loss in
      photobleaching, in living cells revealed that protein aggregates of misfolded
      proteins are dynamic structures that interact with other proteins, such as
      molecular chaperones. Fluorescence correlation spectroscopy analysis detected
      soluble oligomers/aggregates of misfolded proteins in cell extracts. Fluorescence
      resonance energy transfer analysis supported the notion that soluble
      oligomers/aggregates are formed before the formation of inclusions in vivo. Here,
      we reviewed the characteristics of oligomers and aggregates of misfolded
      proteins, with a particular focus on those revealed by spectroscopic analysis,
      and discussed how these oligomers may be toxic to cells.

PMID- 20148963
TI  - Amyloid oligomers: diffuse oligomer-based transmission of yeast prions.
AB  - Prions are infectious proteins, in which self-propagating amyloid conformations
      of proteins are transmitted. The budding yeast Saccharomyces cerevisiae, one of
      the best-studied model eukaryotes, also has prions, and thus provides a tractable
      model system with which to understand the mechanisms of prion phenomena. The
      yeast prions are protein-based heritable elements, such as [PSI(+)], in which
      aggregates of prion proteins are transmitted to daughter cells in a non-Mendelian
      manner. Although the genetic approaches preceded the yeast prion studies, recent
      investigations of the dynamic aspects of the prion proteins have unraveled the
      molecular mechanisms by which prions are propagated and transmitted. In
      particular, several lines of evidence have revealed that the oligomeric species
      of prion proteins dispersed in the cytoplasm are critical for the transmission.
      This review summarizes the topics on the transmissible entities of yeast prions,
      focusing mainly on the Sup35 protein in [PSI(+)].

PMID- 20148964
TI  - Amyloid oligomers: formation and toxicity of Abeta oligomers.
AB  - Alzheimer's disease (AD) is an age-related, progressive degenerative disorder
      that is characterized by synapse and neuron loss in the brain and the
      accumulation of protein-containing deposits (referred to as 'senile plaques') and
      neurofibrillary tangles. Insoluble amyloid beta-peptide (Abeta) fibrillar
      aggregates found in extracellular plaques have long been thought to cause the
      neurodegenerative cascades of AD. However, accumulating evidence suggests that
      prefibrillar soluble Abeta oligomers induce AD-related synaptic dysfunction. The
      size of Abeta oligomers is distributed over a wide molecular weight range (from <
      10 kDa to > 100 kDa), with structural polymorphism in Abeta oligomers of similar
      sizes. Recent studies have demonstrated that Abeta can accumulate in living
      cells, as well as in extracellular spaces. This review summarizes current
      research on Abeta oligomers, focusing on their structures and toxicity mechanism.
      We also discuss possible formation mechanisms of intracellular and extracellular
      Abeta oligomers.

PMID- 20148965
TI  - Amyloid oligomers.

PMID- 20148966
TI  - The pharmacological chaperone isofagomine increases the activity of the Gaucher
      disease L444P mutant form of beta-glucosidase.
AB  - Gaucher disease is caused by mutations in the gene that encodes the lysosomal
      enzyme acid beta-glucosidase (GCase). We have shown previously that the small
      molecule pharmacological chaperone isofagomine (IFG) binds and stabilizes N370S
      GCase, resulting in increased lysosomal trafficking and cellular activity. In
      this study, we investigated the effect of IFG on L444P GCase. Incubation of
      Gaucher patient-derived lymphoblastoid cell lines (LCLs) or fibroblasts with IFG
      led to approximately 3.5- and 1.3-fold increases in L444P GCase activity,
      respectively, as measured in cell lysates. The effect in fibroblasts was
      increased approximately 2-fold using glycoprotein-enrichment, GCase
      immunocapture, or by incubating cells overnight in IFG-free media prior to assay,
      methods designed to maximize GCase activity by reducing IFG carryover and
      inhibition in the enzymatic assay. IFG incubation also increased the lysosomal
      trafficking and in situ activity of L444P GCase in intact cells, as measured by
      reduction in endogenous glucosylceramide levels. Importantly, this reduction was
      seen only following three-day incubation in IFG-free media, underscoring the
      importance of IFG removal to restore lysosomal GCase activity. In mice expressing
      murine L444P GCase, oral administration of IFG resulted in significant increases
      (2- to 5-fold) in GCase activity in disease-relevant tissues, including brain.
      Additionally, eight-week IFG administration significantly lowered plasma chitin
      III and IgG levels, and 24-week administration significantly reduced spleen and
      liver weights. Taken together, these data suggest that IFG can increase the
      lysosomal activity of L444P GCase in cells and tissues. Moreover, IFG is orally
      available and distributes into multiple tissues, including brain, and may thus
      merit therapeutic evaluation for patients with neuronopathic and non
      neuronopathic Gaucher disease.

PMID- 20148967
TI  - The secretome of Campylobacter concisus.
AB  - A higher prevalence of Campylobacter concisus and higher levels of IgG antibodies
      specific to C. concisus in Crohn's disease patients than in controls were
      recently detected. In this study, 1D and 2D gel electrophoresis coupled with LTQ
      FT-MS and QStar tandem MS, respectively, were performed to characterize the
      secretome of a C. concisus strain isolated from a Crohn's disease patient. Two
      hundred and one secreted proteins were identified, of which 86 were
      bioinformatically predicted to be secreted. Searches were performed on the genome
      of C. concisus strain 13826, and 25 genes that have been associated with
      virulence or colonization in other organisms were identified. The zonula
      occludens toxin was found only in C. concisus among the Campylobacterales,
      although expanded searches revealed that this protein was present in two epsilon
      proteobacterial species from extreme marine environments. Alignments and
      structural threading indicated that this toxin shared features with that of other
      virulent pathogens, including Neisseria meningitidis and Vibrio cholerae. Further
      comparative analyses identified several associations between the secretome of C.
      consisus and putative virulence factors of this bacterium. This study has
      identified several factors putatively associated with disease outcome, suggesting
      that C. concisus is a pathogen of the gastrointestinal tract.

PMID- 20148968
TI  - Cellulose crystallinity--a key predictor of the enzymatic hydrolysis rate.
AB  - The enzymatic hydrolysis of cellulose encounters various limitations that are
      both substrate- and enzyme-related. Although the crystallinity of pure cellulosic
      Avicel plays a major role in determining the rate of hydrolysis by cellulases
      from Trichoderma reesei, we show that it stays constant during enzymatic
      conversion. The mode of action of cellulases was investigated by studying their
      kinetics on cellulose samples. A convenient method for reaching intermediate
      degrees of crystallinity with Avicel was therefore developed and the initial rate
      of the cellulase-catalyzed hydrolysis of cellulose was demonstrated to be
      linearly proportional to the crystallinity index of Avicel. Despite correlation
      with the adsorption capacity of cellulases onto cellulose, at a given enzyme
      loading, the initial enzymatic rate continued to increase with a decreasing
      crystallinity index, even though the bound enzyme concentration stayed constant.
      This finding supports the determinant role of crystallinity rather than
      adsorption on the enzymatic rate. Thus, the cellulase activity and initial rate
      data obtained from various samples may provide valuable information about the
      details of the mechanistic action of cellulase and the hydrolysable/reactive
      fractions of cellulose chains. X-ray diffraction provides insight into the mode
      of action of Cel7A from T. reesei. In the conversion of cellulose, the (021) face
      of the cellulose crystal was shown to be preferentially attacked by Cel7A from T.
      reesei.

PMID- 20148969
TI  - Photoregulation of DNA transcription by using photoresponsive T7 promoters and
      clarification of its mechanism.
AB  - With the use of photoresponsive T7 promoters tethering two 2'-methylazobenzenes
      or 2',6'-dimethylazobenzenes, highly efficient photoregulation of DNA
      transcription was obtained. After UV-A light irradiation (320-400 nm), the rate
      of transcription with T7 RNA polymerase and a photoresponsive promoter involving
      two 2',6'-dimethylazobenzenes was 10-fold faster than that after visible light
      irradiation (400-600 nm). By attaching a nonmodified azobenzene and 2',6'
      dimethylazobenzene at the two positions, respectively, and by utilizing the
      different cis-->trans thermal stability between cis-nonmodified azobenzene and
      cis-2',6'-dimethylazobenzene, four species of T7 promoter (cis-cis, trans-cis,
      cis-trans, and trans-trans) were obtained. The four species showed
      transcriptional activity in the order of cis-cis > cis-trans > trans-cis > trans
      trans. Kinetic analysis revealed that the K(m) for the cis-cis promoter (both of
      the introduced azobenzene derivatives were in the cis form) and T7 RNA polymerase
      was 68 times lower than that for the trans-trans form, indicating that high
      photoregulatory efficiency was mainly due to a remarkable difference in affinity
      for RNA polymerase. The present approach is promising for the creation of
      biological tools for artificially controlling gene expression, and as a
      photocontrolled system for supplying RNA fuel for RNA-powered molecular
      nanomachines.

PMID- 20148970
TI  - Crystal structure of a glycoside hydrolase family 6 enzyme, CcCel6C, a cellulase
      constitutively produced by Coprinopsis cinerea.
AB  - The basidiomycete Coprinopsis cinerea produces the glycoside hydrolase family 6
      enzyme CcCel6C at low and constitutive levels. CcCel6C exhibits unusual
      cellobiohydrolase activity; it hydrolyses carboxymethyl cellulose, which is a
      poor substrate for typical cellobiohydrolases. Here, we determined the crystal
      structures of CcCel6C unbound and in complex with p-nitrophenyl beta-D
      cellotrioside and cellobiose. CcCel6C consists of a distorted seven-stranded
      beta/alpha barrel and has an enclosed tunnel, which is observed in other
      cellobiohydrolases from ascomecetes Hypocrea jecorina (HjeCel6A) and Humicola
      insolens (HinCel6A). In HjeCel6A and HinCel6A, ligand binding produces a
      conformational change that narrows this tunnel. In contrast, the tunnel remains
      wide in CcCel6C and the conformational change appears to be less favourable than
      in HjeCel6A and HinCel6A. The ligand binding cleft for subsite -3 of CcCel6C is
      also wide and is rather similar to that of endoglucanase. These results suggest
      that the open tunnel and the wide cleft are suitable for the hydrolysis of
      carboxymethyl cellulose.

PMID- 20148971
TI  - A hybrid clustering of protein binding sites.
AB  - The Protein Data Bank contains the description of approximately 27 000 protein
      ligand binding sites. Most of the ligands at these sites are biologically active
      small molecules, affecting the biological function of the protein. The
      classification of their binding sites may lead to relevant results in drug
      discovery and design. Clusters of similar binding sites were created here by a
      hybrid, sequence and spatial structure-based approach, using the OPTICS
      clustering algorithm. A dissimilarity measure was defined: a distance function on
      the amino acid sequences of the binding sites. All the binding sites were
      clustered in the Protein Data Bank according to this distance function, and it
      was found that the clusters characterized well the Enzyme Commission numbers of
      the entries. The results, carefully color coded by the Enzyme Commission numbers
      of the proteins, containing the 20 967 binding sites clustered, are available as
      html files in three parts at http://pitgroup.org/seqclust/.

PMID- 20148972
TI  - A Caenorhabditis elegans model of orotic aciduria reveals enlarged lysosome
      related organelles in embryos lacking umps-1 function.
AB  - Gut granules are cell type-specific lysosome-related organelles found within the
      intestinal cells of Caenorhabditis elegans. To investigate the regulation of
      lysosome-related organelle size, we screened for C. elegans mutants with
      substantially enlarged gut granules, identifying alleles of the vacuolar-type
      H(+)-ATPase and uridine-5'-monophosphate synthase (UMPS)-1. UMPS-1 catalyzes the
      conversion of orotic acid to UMP; this comprises the two terminal steps in de
      novo pyrimidine biosynthesis. Mutations in the orthologous human gene UMPS result
      in the rare genetic disease orotic aciduria. The umps-1(-) mutation promoted the
      enlargement of gut granules to 250 times their normal size, whereas other
      endolysosomal organelles were not similarly affected. UMPS-1::green fluorescent
      protein was expressed in embryonic and adult intestinal cells, where it was
      cytoplasmically localized and not obviously associated with gut granules. Whereas
      the umps-1(-) mutant is viable, combination of umps-1(-) with mutations
      disrupting gut granule biogenesis resulted in synthetic lethality. The effects of
      mutations in pyr-1, which encodes the enzyme catalyzing the first three steps of
      de novo pyrimidine biosynthesis, did not phenotypically resemble those of umps-1(
      ); instead, the synthetic lethality and enlargement of gut granules exhibited by
      the umps-1(-) mutant was suppressed by pyr-1(-). In a search for factors that
      mediate the enlargement of gut granules in the umps-1(-) mutant, we identified
      WHT-2, an ABCG transporter previously implicated in gut granule function. Our
      data suggest that umps-1(-) leads to enlargement of gut granules through a build
      up of orotic acid. WHT-2 possibly facilitates the increase in gut granule size of
      the umps-1(-) mutant by transporting orotic acid into the gut granule and
      promoting osmotically induced swelling of the compartment.

PMID- 20148973
TI  - Characterization of ACC deaminase from the biocontrol and plant growth-promoting
      agent Trichoderma asperellum T203.
AB  - 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity was evaluated in the
      biocontrol and plant growth-promoting fungus Trichoderma asperellum T203. Fungal
      cultures grown with ACC as the sole nitrogen source showed high enzymatic
      activity. The enzyme encoding gene (Tas-acdS) was isolated, and an average 3.5
      fold induction of the gene by 3 mM ACC was detected by real-time PCR. Escherichia
      coli bacteria carrying the intron-free cDNA of Tas-acdS cloned into the vector
      pAlter-EX1 under the control of the tac promoter revealed specific ACC deaminase
      (ACCD) activity and the ability to promote canola (Brassica napus) root
      elongation in pouch assays. RNAi silencing of the ACCD gene in T. asperellum
      showed decreased ability of the mutants to promote root elongation of canola
      seedlings. These data suggest a role for ACCD in the plant root growth-promotion
      effect by T. asperellum.

PMID- 20148974
TI  - A reason for overlap peaks in direct sequencing of rRNA gene ITS in Pleurotus
      nebrodensis.
AB  - To examine why we failed in direct sequencing of rRNA gene internal transcribed
      spacer (ITS) in Pleurotus nebrodensis, we obtained monokaryons of P. nebrodensis
      (00489 and 00491) using a protoplast monokaryonization technique. PCR products of
      ITS amplifications were sequenced. There was a base pair insertion/deletion
      difference between the two nuclei of P. nebrodensis that led to failure in direct
      sequencing.

PMID- 20148975
TI  - The association of glycolytic enzymes from yeast confers resistance against
      inhibition by trehalose.
AB  - During stress, many organisms accumulate compatible solutes. These solutes must
      be eliminated upon return to optimal conditions as they inhibit cell metabolism
      and growth. In contrast, enzyme interactions optimize metabolism through
      mechanisms such as channeling of substrates. It was decided to test the
      (compatible solute) trehalose-mediated inhibition of some yeast glycolytic
      pathway enzymes known to associate and whether inhibition is prevented when
      enzymes are allowed to associate. Trehalose inhibited the isolated glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) and hexokinase (HXK), but not aldolase (ALD)
      nor phosphoglycerate kinase (PGK). When these enzymes were mixed in pairs, both
      GAPDH and HXK were protected by either ALD or PGK acquiring the inhibition
      behavior of the resistant enzyme. GAPDH was not protected by HXK, albumin or
      lactate dehydrogenase (LDH). Also, ALD did not protect glucose 6-phosphate
      dehydrogenase (G6PDH), suggesting that protection is specific. In yeast cell
      extracts, fermentation was resistant to trehalose inhibition, suggesting all
      enzymes involved in the glucose-dependent production of ethanol were stabilized.
      It is suggested that during the yeast stress response, enzyme association
      protects some metabolic pathways against trehalose-mediated inhibition.

PMID- 20148976
TI  - How many carriers are there?

PMID- 20148977
TI  - Limited blood sampling for pharmacokinetic dose tailoring of FVIII in the
      prophylactic treatment of haemophilia A.
AB  - The aim of this study was to evaluate the use of limited blood sampling and
      Bayesian analysis to estimate the pharmacokinetics (PK) and tailor the dose of
      factor VIII (FVIII) in an individual patient. In a Bayesian analysis, PK
      parameters are estimated from only a few plasma concentration measurements, using
      a previously established PK model. First the necessary model was created using
      intense blood sampling FVIII data from 10 patients. Then FVIII data from another
      21 patients were used for 'clinical' evaluation. Three scenarios were created
      retrospectively by reduction of the original 7-sample data set; blood sampling at
      4, 24 and 48 h, at 8 and 30 h and at 24 h after the infusion. PK parameters were
      estimated for each individual using Bayesian analysis and compared with those
      obtained using conventional methods from the full data. The accuracy of
      predictions of FVIII levels during prophylactic treatment 5-17 months later and
      implications for dose tailoring were also investigated. Blood sampling at 4, 24
      and 48 h was found to give practically the same PK information as a full,
      conventional (7-10-sample) study. Even a single 24-h FVIII level provided
      adequate data for initial dose tailoring and gave predictions of FVIII levels 5
      17 months later that were not appreciably worse than predictions based on the
      full PK analysis. By contrast, dose tailoring based on body weight failed
      completely. In conclusion, PK-based dose tailoring of FVIII can be performed
      using limited blood sampling during prophylactic treatment.

PMID- 20148978
TI  - Mortality and causes of death in Italian persons with haemophilia, 1990-2007.
AB  - Although a number of studies have analysed so far the causes of death and the
      life expectancy in haemophilic populations, no investigations have been conducted
      among Italian haemophilia centres. Thus, the aim of this study was to investigate
      mortality, causes of deaths, life expectancy and co-morbidities in Italian
      persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died
      between 1980 and 2007 were retrospectively collected in the 30 centres who are
      members of the Italian Association of Haemophilia Centres that chose to
      participate. The mortality rate ratio standardized to the male Italian population
      (SMR) was reduced during the periods 1990-1999 and 2000-2007 such that during the
      latter, death rate overlapped that of the general population (SMR 1990-1999: 1.98
      95% CI 1.54-2.51; SMR 2000-2007: 1.08 95% CI 0.83-1.40). Similarly, life
      expectancy in the whole haemophilic population increased in the same period (71.2
      years in 2000-2007 vs. 64.0 in 1990-1999), approaching that of the general male
      population. While human immunodeficiency virus infection was the main cause of
      death (45%), 13% of deaths were caused by hepatitis C-associated complications.
      The results of this retrospective study show that in Italian PWH improvements in
      the quality of treatment and global medical care provided by specialized
      haemophilia centres resulted in a significantly increased life expectancy.

PMID- 20148980
TI  - Thrombin generation in haemophilia A patients with mutations causing factor VIII
      assay discrepancy.
AB  - Up to 40% of patients with mild haemophilia A have a discrepancy whereby factor
      VIII (FVIII) measurements by a two-stage chromogenic assay (FVIII:C(CH)) are
      disproportionately reduced compared with the FVIII one-stage clotting value
      (FVIII:C). Which assay best reflects the coagulation potential and clinical
      phenotype in this patient group is of clinical significance, yet remains unclear.
      We have assessed the global coagulant ability of haemophilia patients with FVIII
      assay discrepancy using calibrated automated thrombography (CAT). A total of 18
      patients with mutations Arg531His/Cys or Arg698Trp causing FVIII discrepancy were
      investigated, together with 12 haemophilia patients with concordant FVIII values
      and 15 normal controls. Factor VIII levels in all patients and controls were
      measured using both one-stage clotting assay and two-stage chromogenic assay.
      Thrombin generation was assessed in platelet-poor plasma by CAT using a low
      tissue factor concentration (1 pm). FVIII:C(CH) values were below normal in all
      patients, and in the discrepant group were between 1.5- and 8-fold lower than
      FVIII:C values. CAT parameters were affected in all haemophilia patients. The
      endogenous thrombin potential (ETP) was reduced to 58-67% of the mean normal
      value (1301 nm min(-1)), whereas peak thrombin was further reduced to 27-30% of
      the mean normal value (178 nm) in both discrepant and concordant patient groups.
      Analysis of the discrepant patient group showed the most significant correlation
      between the one-stage FVIII:C assay and ETP (r(2) = 0.44) and peak thrombin
      parameters (r(2) = 0.27).

PMID- 20148979
TI  - Radioisotope synoviorthesis with Holmium-166-chitosan complex in haemophilic
      arthropathy.
AB  - Radiosynoviorthesis is a safe and easy method for synovectomy in haemophilic
      arthropathy. Various agents have been used in radiosynoviorthesis, especially
      newly developed agent Holmium-166-chitosan complex has good clinical outcome.
      This study analysed clinical results and radiologic evaluation of radioisotope
      synoviorthesis using Holmium-166-chitosan complex in haemophilic arthropathy.
      From March 2001 to December 2003, 58 radiosynoviorthesis were performed in 53
      haemophiliacs. The average age at procedure was 13.8 years. The Arnold and
      Hilgartner stage of the patients was from I to IV. Holmium-166-chitosan complex
      was injected in 31 ankle joints, 19 elbow joints and 8 knee joints. Average
      follow-up was 33 months since primary procedure. The range of motion of each
      joint, frequency of intra-articular bleeding and factor dose used were analysed
      for clinical assessment. There was no significant improvement of range of motion
      in affected joints. After procedure, the average frequency of bleeding of the
      elbow joint has decreased from 3.76 to 0.47 times per month, the knee joint from
      5.87 to 1.12 times per month, and the ankle joint from 3.62 to 0.73 times per
      month respectively (P < 0.05). After treatment, the average coagulation factor
      dose injected was significantly decreased to 779.3 units per month from 2814.8
      units per month before treatment (P < 0.001). Radioisotope synoviorthesis with
      Holmium-166-chitosan complex in haemophilic arthropathy is a very safe and simple
      procedure with the expectation of a satisfactory outcome without serious
      complication. It has excellent bleeding control effect on target joint and the
      need for substitution of coagulation factor concentrate can be reduced.

PMID- 20148981
TI  - Alarmingly high prevalence of obesity in haemophilia in the state of Mississippi.
AB  - The state of Mississippi has consistently been ranked as the state with most
      number of obese people in the United States with prevalence rates of >30%. Our
      aims in this study were to estimate the prevalence of overweight and obesity in
      children and adults diagnosed with haemophilia in Mississippi, and to assess
      whether race/ethnicity and the severity of haemophilia are important risk
      factors. A retrospective chart review was performed for all haemophilic patients
      seen at the Mississippi Hemophilia Treatment Center. Patients were classified
      into two major age groups: age 2-19.9 years and > or =20 years. Body mass index
      (BMI) was calculated from the height and weight in kg m(-2) from the last clinic
      visit. Out of a total of 132 haemophilic patients, 61% were white and 37% were
      African American. Overall, 51% of the haemophilic patients were either obese or
      overweight. The prevalence of obesity in the adult (> or =20 years old)
      haemophilic patients was 36% and an additional 32% were overweight. A
      significantly greater proportion of patients >20 years old were overweight or
      obese as compared with the patients in the 2-19.9 year age range (P < 0.002).
      However, race/ethnicity and severity of haemophilia were not significant risk
      factors for overweight and obesity. There is a very high prevalence of obesity in
      the Mississippi haemophilic population, especially in adults. Particular
      attention at clinic visits should be paid to the BMI in order to identify
      patients that are overweight or obese to allow for early and appropriate
      intervention.

PMID- 20148982
TI  - Migraine education improves quality of life in a primary care setting.
AB  - OBJECTIVE: The objective of this study was to evaluate the effectiveness of the
      Mercy Migraine Management Program (MMMP), an educational program for physicians
      and patients. The primary outcome was change in headache days from baseline at 3,
      6, and 12 months. Secondary outcomes were changes in migraine-related disability
      and quality of life, worry about headaches, self-efficacy for managing migraines,
      emergency room (ER) visits for headache, and satisfaction with headache care.
      BACKGROUND: Despite progress in the understanding of the pathophysiology of
      migraine and development of effective therapeutic agents, many practitioners and
      patients continue to lack the knowledge and skills to effectively manage
      migraine. Educational efforts have been helpful in improving the quality of care
      and quality of life for migraine sufferers. However, little work has been
      performed to evaluate these changes over a longer period of time. Also, there is
      a paucity of published research evaluating the influence of education about
      migraine management on cognitive and emotional factors (for example, self
      efficacy for managing headaches, worry about headaches). METHODS: In this open
      label, prospective study, 284 individuals with migraine (92% female, mean age =
      41.6) participated in the MMMP, an educational and skills-based program. Of the
      284 who participated in the program, 228 (80%) provided data about their headache
      frequency, headache-related disability (as measured by the Headache Impact Test-6
      (HIT-6), migraine-specific quality of life (MSQ), worry about headaches, self
      efficacy for managing headaches, ER visits for headaches, and satisfaction with
      care at 4 time points over 12 months (baseline, 3 months, 6 months, 12 months).
      RESULTS: Overall, 46% (106) of subjects reported a 50% or greater reduction in
      headache frequency. Over 12 months, patients reported fewer headaches and
      improvement on the HIT-6 and MSQ (all P < .001). The improvement in headache
      impact and quality of life was greater among those who had more worry about their
      headaches at baseline. There were also significant improvements in "worry about
      headaches,""self-efficacy for managing headaches," and "satisfaction with
      headache care." CONCLUSION: The findings demonstrate that patients participating
      in the MMMP reported improvements in their headache frequency as well as the
      cognitive and emotional aspects of headache management. This program was
      especially helpful among those with high amounts of worry about their headaches
      at the beginning of the program. The findings from this study are impetus for
      further research that will more clearly evaluate the effects of education and
      skill development on headache characteristics and the emotional and cognitive
      factors that influence headache.

PMID- 20148983
TI  - Commentary: what conclusions can we draw from recent analyses of anesthesia
      provider model and patient outcomes?

PMID- 20148984
TI  - Long-term trends in Medicare payments in the last year of life.
AB  - OBJECTIVE: To update research on Medicare payments in the last year of life. DATA
      SOURCES: Continuous Medicare History Sample, containing annual summaries of
      claims data on a 5 percent sample from 1978 to 2006. STUDY DESIGN: Analyses were
      based on elderly beneficiaries in fee for service. For each year, Medicare
      payments were assigned either to decedents (persons in their last year) or to
      survivors (all others). RESULTS: The share of Medicare payments going to persons
      in their last year of life declined slightly from 28.3 percent in 1978 to 25.1
      percent in 2006. After adjustment for age, sex, and death rates, there was no
      significant trend. CONCLUSIONS: Despite changes in the delivery of medical care
      over the last generation, the share of Medicare expenditures going to
      beneficiaries in their last year has not changed substantially.

PMID- 20148986
TI  - Production of interleukin-10 in serum and erythropoietin sensitivity in ESRD
      patients on hemodialysis.
AB  - One of the clinical consequences of aberrant cytokines production in patients
      with end stage renal disease (ESRD) may be impaired erythropoiesis. To determine
      the interleukin (IL)-10 levels in ESRD patients on regular hemodialysis (HD) with
      good and poor response to recombinant human erythropoietin (Epo). Two groups of
      ESRD-HD patients were evaluated; 48 high epo HD patients and 32 low epo HD
      patients were evaluated for some laboratory tests and Interleukin-10 by ELISA.
      The production of IL-10 is decreased in HD with low epo group than high epo group
      32.4 +/- 7.9 vs. 45 +/- 6.9 pg/ml (P < 0.001). IL-10 level is well correlated
      with CRP, ESR, Ferritin, Epo dose, and EPO/Hb ratio in ESRD-HD patients. These
      findings suggest that IL-10 is playing a part in affecting the response to EPO,
      even in the absence of any obvious infection or inflammatory condition.

PMID- 20148985
TI  - Predictors of chain acquisition among independent dialysis facilities.
AB  - OBJECTIVE: To determine the predictors of chain acquisition among independent
      dialysis providers. DATA SOURCES: Retrospective facility-level data combined from
      CMS Cost Reports, Medical Evidence Forms, Annual Facility Surveys, and claims for
      1996-2003. STUDY DESIGN: Independent dialysis facilities' probability of
      acquisition by a dialysis chain (overall and by chain size) was estimated using a
      discrete time hazard rate model, controlling for financial and clinical
      performance, practice patterns, market factors, and other facility
      characteristics. DATA COLLECTION: The sample includes all U.S. freestanding
      dialysis facilities that report not being chain affiliated for at least 1 year
      between 1997 and 2003. PRINCIPAL FINDINGS: Above-average costs and better quality
      outcomes are significant determinants of dialysis chain acquisition. Facilities
      in larger markets were more likely to be acquired by a chain. Furthermore, small
      dialysis chains have different acquisition strategies than large chains.
      CONCLUSIONS: Dialysis chains appear to employ a mix of turn-around and cream
      skimming strategies. Poor financial health is a predictor of chain acquisition as
      in other health care sectors, but the increased likelihood of chain acquisition
      among higher quality facilities is unique to the dialysis industry. Significant
      differences among predictors of acquisition by small and large chains reinforce
      the importance of using a richer classification for chain status.

PMID- 20148987
TI  - Comparison of a point of care device against current laboratory methodology using
      citrated and EDTA samples for the determination of D-dimers in the exclusion of
      proximal deep vein thrombosis.
AB  - D-dimer estimation is a routine part of diagnostic algorithms for the exclusion
      of venous thromboembolism (VTE). We evaluated a point of care device, Biosite
      Triage (Inverness Medical UK, Cheshire, UK) for the estimation of D-dimers in
      both samples taken into citrate and EDTA against our routine laboratory D-dimer
      (Liatest D-dimer, Diagnostica Stago, Reading, UK) performed on the STA-R
      Evolution. With informed consent, 102 consecutive patients presenting with
      possible deep vein thrombosis (DVT) were enrolled and D-dimers along with Wells
      scores and compression ultrasonography (CUS) were recorded. Using the
      manufacturers' recommended cut offs of 500 microg/l fibrinogen equivalent units
      and 400 microg/l for the Stago and Triage, respectively, sensitivity,
      specificity, positive and negative predictive values were calculated. These were
      1.00, 0.42, 0.17, and 1.00 for the Triage machine using citrate samples, 1.00,
      0.32, 0.14, and 1.00 using EDTA samples and 1.00, 0.29, 0.16, and 1.00 for the
      Stago Liatest assay, respectively. Three patients had significantly higher
      results for the Stago Liatest D-dimer assay compared with the Biosite Triage
      device although ultrasound scans were negative. CONCLUSION: The Biosite Triage D
      dimer assay performed on either citrate or EDTA samples is comparable with the
      Stago Liatest laboratory D-dimer assay when used in conjunction with clinical
      pretest probability scoring and CUS for the exclusion of DVT.

PMID- 20148988
TI  - Are 10 min of seating enough to guarantee stable haemoglobin and haematocrit
      readings for the athlete's biological passport?
AB  - Haemoglobin (Hb) and haematocrit (Hct) are measured as indirect markers of doping
      in athletes. We studied the effect of posture on these parameters in a typical
      antidoping setting. Venous blood samples were obtained from nine endurance
      athletes (six males, three females) and nine control subjects (six males, three
      females) immediately and after 5, 10, 15, 20 and 30 min after having adopted a
      seated position from normal daily activity. Hb (CV 0.72%) and Hct (CV 0.87%) were
      determined using an automated cell counter, plasma volume changes were
      calculated. Differences between the time points, gender and groups were
      calculated using a mixed-model procedure. Significant changes were observed in
      the first 10 min after sitting down but no further changes were noted between 10
      and 30 min. Mean directional change for Hb and Hct between 0 min and the average
      of the period from 10 to 30 min was -2.4% (-0.35 g/dl) for Hb and -2.7% (-1.2%)
      for Hct. Plasma volume increased accordingly. Neither group nor gender had
      significant effects. Under typical conditions encountered during blood testing in
      doping control, a period of 10 min in a seated position is sufficient for the
      vascular volumes to re-equilibrate and to adapt to the new posture.

PMID- 20148989
TI  - Immunomagnetic quantification of circulating tumor cells in patients with
      urothelial cancer.
AB  - OBJECTIVES: To evaluate the relationship between circulating tumor cells (CTC)
      and clinical parameters in metastatic urothelial cancer (UC). METHODS: CTC were
      enumerated with the CellSearch System, which was developed using an EpCAM
      antibody-based immunomagnetic capture and automated staining methodology. UC cell
      lines (RT4, T24, TCC, UMUC3 and 253J) and mixed blood from healthy males were
      analyzed. Blood samples from 16 patients without metastatic UC and 20 patients
      with metastatic UC were also analyzed. RESULTS: The accuracy and reliability of
      the assay were determined using spiked UC cells (RT4 and T24), which showed a
      strong linear correlation (r = 0.99) and recovery rate of 94% +/- 5% and 84% +/-
      6%, respectively. Three UC cell lines (TCC, UMUC3 and 253J) tested negative. The
      16 patients without metastatic UC tested negative as well. Eleven (55%) patients
      with metastatic UC tested positive for at least one CTC. Seven (35%) had two or
      more CTC. Significantly more CTC were seen in patients with two or more sites of
      metastasis than those with one site of metastasis (P = 0.004). CONCLUSIONS: Based
      on these findings, CTC could represent a potential marker to monitor the response
      to chemotherapy in patients with metastatic UC.

PMID- 20148990
TI  - Predicting the probability of significant prostate cancer in Japanese men with
      serum prostate-specific antigen less than 10 ng/mL: development of a novel pre
      biopsy nomogram.
AB  - OBJECTIVES: To develop and assess a new nomogram incorporating pre-biopsy
      clinical data to predict significant prostate cancer in Japanese men with a serum
      prostate-specific antigen (PSA) level of less than 10 ng/mL. METHODS: We
      collected pre-biopsy data from 620 men with a serum total PSA of less than 10
      ng/mL. They included 491 men with a negative biopsy and 129 men who were
      confirmed to have histological prostate cancer and subsequently underwent radical
      prostatectomy. Clinically significant tumors were defined as those with a tumor
      volume larger than 0.5 mL and/or a Gleason score of 7 or more. RESULTS: One
      hundred and seven prostatectomy patients had clinically significant cancers.
      Stepwise multivariate logistic regression analysis showed that digital rectal
      examination findings, PSA adjusted for transition zone volume and free-to-total
      PSA ratio were the significant independent predictors of significant cancers (P <
      0.0001). Using these pre-biopsy independent factors, a nomogram was developed to
      predict significant cancers. According to a receiver operating characteristics
      analysis, the nomogram showed an area under the curve of 0.831. CONCLUSION: This
      represents the first nomogram to predict the probability of clinically
      significant cancers before biopsy. This tool is most likely to be useful in the
      management of patients with moderate to elevated PSA.

PMID- 20148991
TI  - Functional specialization and ontogenetic scaling of limb anatomy in Alligator
      mississippiensis.
AB  - Crocodylians exhibit a fascinating diversity of terrestrial gaits and limb
      motions that remain poorly described and are of great importance to understanding
      their natural history and evolution. Their musculoskeletal anatomy is pivotal to
      this diversity and yet only qualitative studies of muscle-tendon unit anatomy
      exist. The relative masses and internal architecture (fascicle lengths and
      physiological cross-sectional areas) of muscles of the pectoral and pelvic limbs
      of American alligators (Alligator mississippiensis Daudin 1801) were recorded for
      an ontogenetic series of wild specimens (n = 15, body masses from 0.5 to 60 kg).
      The data were analysed by reduced major axis regression to determine scaling
      relationships with body mass. Physiological cross-sectional areas and therefore
      muscle force-generating capacity were found to be greater in the extensor (anti
      gravity) muscles of the pelvic limb than in the pectoral limb, reflecting how
      crocodylians differ from mammals in having greater loading of the hindlimbs than
      the forelimbs. Muscle masses and architecture were generally found to scale
      isometrically with body mass, suggesting an ontogenetic decrease in terrestrial
      athleticism. This concurs with the findings of previous studies showing
      ontogenetic decreases in limb bone length and the general scaling principle of a
      decline of strength : weight ratios with increasing size in animals. Exceptions
      to isometric scaling found included positive allometry in fascicle length for
      extensor musculature of both limbs, suggesting an ontogenetic increase in working
      range interpreted as increasing postural variability - in particular the major
      hip extensors - the interpretation of which is complicated by previous described
      ontogenetic increase of moment arms for these muscles.

PMID- 20148992
TI  - The elastic network of articular cartilage: an immunohistochemical study of
      elastin fibres and microfibrils.
AB  - The elastic network of articular cartilage was investigated by
      immunohistochemistry using specific antibodies to elastin and fibrillin-1.
      Articular cartilage was dissected from defined regions of bovine
      metacarpophalangeal joints. Elastin fibres and microfibrils were dual
      immunostained by labelling with distinct fluorescent dyes. A conventional
      fluorescence microscope combined with a polarized light filter was used to study
      the organization and degree of colocalization of elastin fibres, microfibrils and
      of the collagen network. We observed an elaborately organized elastic network. In
      the uppermost superficial zone, where few cells were present, elastin fibres and
      microfibrils formed a dense three dimensional network showing some degree of
      colocalization. The thickness and organization of this elastic network varied
      dramatically from region to region and was most extensive in the metacarpal
      palmar region. In the middle and deep zones, very few elastin fibres were
      observed but microfibrils formed a network in the inter-territorial matrix and
      dense network around the cells. Our finding of a three dimensional network of
      dense, well organized elastin fibres and microfibrils in the surface zone of the
      articular cartilage matrix, and a dense network of microfibrils around the cells
      deeper into the tissue suggests the elastic network could play both a mechanical
      and a biological role in articular cartilage.

PMID- 20148993
TI  - Population dynamics of an Arctiid caterpillar-tachinid parasitoid system using
      state-space models.
AB  - 1. Population dynamics of insect host-parasitoid systems are important in many
      natural and managed ecosystems and have inspired much ecological theory. However,
      ecologists have a limited knowledge about the relative strengths of species
      interactions, abiotic effects and density dependence in natural host-parasitoid
      dynamics. Statistical time-series analyses would be more informative by
      incorporating multiple factors, measurement error and noisy dynamics. 2. We use a
      novel maximum likelihood and model-selection analysis of a state-space model for
      host-parasitoid dynamics to examine 21 years of annual census data for woolly
      bear caterpillars (Platyprepia virginalis) and their locally host-specific
      tachinid parasitoids (Thelaira americana). 3. Caterpillar densities varied by
      three orders of magnitude and were driven by density dependence and precipitation
      from the previous March but not detectably by parasitoids, despite variable and
      sometimes high (>50%) parasitism. 4. Fly fluctuations, as estimated from per cent
      parasitism, were affected by density dependence and precipitation from the
      previous July. There was marginal evidence that host abundance drives fly
      fluctuations as a generic linear effect but no evidence for classical Nicholson
      Bailey coupling. 5. The state-space model analysis includes new methods for
      likelihood calculation and allows a balanced consideration of effect magnitude
      and statistical significance in a nonlinear model with multiple alternative
      explanatory variables.

PMID- 20148994
TI  - Differential effects of experimental increases in sociality on ectoparasites of
      free-ranging raccoons.
AB  - 1. Parasite transmission depends on the rate at which hosts come into contact
      with one another or the infectious stages of parasites. However, host contact
      rates and their influence on parasite transmission are difficult to quantify in
      natural settings and can fluctuate with host behaviour and the ecological
      constraints of parasites. 2. We investigated how experimental increases in rates
      of contact and social aggregation affected ectoparasite prevalence and intensity
      of free-ranging raccoons (Procyon lotor). Twelve independent raccoon populations
      were subjected to differential resource provisions for 2 years: a clumped food
      distribution to aggregate hosts (n = 5 aggregated populations), a dispersed food
      distribution to control for the effects of food without aggregating hosts (n = 3)
      and a no food treatment (n = 4). 3. Remote cameras indicated that aggregation
      sizes and rates of contact were three to four times greater in aggregated
      compared with that in non-aggregated populations. The number of ticks (adult
      Dermacentor variabilis) on raccoons in aggregated populations was 1.5-2.5 times
      greater from May to July, the primary time of tick seasonal occurrence.
      Conversely, louse (Trichodectes octomaculatus) populations were c. 40% sparser on
      male raccoons in aggregated (compared with that in non-aggregated) populations
      because of greater overdispersion of lice and a larger number of male hosts
      harbouring fewer parasites. No treatment-related differences were found among
      fleas (Orchopeas howardi). 4. These results were not consistent with our current
      understanding of parasite transmission; greater rates of host sociality led to
      increases in a parasite that does not rely on host contact for transmission
      (ticks) and declines in a parasite that depends on host contact for transmission
      (lice). We concluded that D. variabilis increased in aggregated sites because
      they can detect and seek out hosts and were more likely to drop off after
      obtaining a blood meal and re-attach to raccoons in these locations. Several
      factors may have contributed to sparser louse populations on male hosts,
      including a dilution effect that lowered per capita infestation levels. 5. These
      results indicate that ectoparasites can interact in unique ways with their hosts
      that are not consistent with other types of parasite species or models of their
      transmission.

PMID- 20148995
TI  - Inactivation of wine spoilage yeasts Dekkera bruxellensis using low electric
      current treatment (LEC).
AB  - AIMS: The objective of this study was to investigate the inactivation of a
      selected yeast Dekkera bruxellensis strain 4481 in red wine by application of low
      electric current treatment (LEC). METHODS AND RESULTS: LEC (200 mA) was applied
      for 60 days to a red wine, Montepulciano d'Abruzzo, in an alternative strategy to
      the SO(2) addition during wine storage. The LEC effect on both cell activity and
      microflora viability was assessed. LEC decreased significantly the survival
      viable cells and increased the death rate of D. bruxellensis strain 4481 yeast. A
      final comparison was made of the main physico-chemical parameters of the wine
      after the different treatments. The study suggests the importance of an
      appropriate LEC treatment which limits wine deterioration in terms of off
      flavours synthesis. CONCLUSIONS: The results demonstrate that the growth of
      undesirable Dekkera can be inhibited by low voltage treatment; LEC was shown to
      be useful to prevent wine spoilage and has the potential of being a concrete
      alternative method for controlling wine spoilage. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Wine spoilage can be avoided by preventing the growth of undesirable
      Dekkera yeasts, through the effective use of LEC in the winemaking process.

PMID- 20148996
TI  - Effect of pps disruption and constitutive expression of srfA on surfactin
      productivity, spreading and antagonistic properties of Bacillus subtilis 168
      derivatives.
AB  - AIMS: To analyse the effects of plipastatin operon disruption and constitutive
      expression of surfactin operon in Bacillus subtilis 168 on surfactin
      productivity, in vitro invasive growth and antagonism against fungi. METHODS AND
      RESULTS: The srfA native promoter was replaced by the constitutive promoter
      P(repU) in B. subtilis 168 after integration of a functional sfp gene. Moreover,
      the plipastatin synthesis was further disrupted in the B. subtilis 168
      derivatives. In liquid media, an earlier and higher expression of P(repU), than
      that found with P(srfA), led to a specific surfactin production fivefold higher
      after 6 h of culture. On solid media, not only the invasive growth and the
      haemolytic activity but also the antifungal activity of the constitutive strains
      were improved when compared to the parental strain BBG111. As expected, the
      disruption of the plipastatin operon strongly reduced in vitro antifungal
      properties but, interestingly, enhanced specific surfactin production (1.47 g g(
      1) of biomass), spreading behaviour and haemolytic activity of the strains.
      CONCLUSIONS: This work demonstrates for the first time the interdependency of
      surfactin and plipastatin regarding their biosynthesis as well as their influence
      on the biological activities of the producing strain. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The constitutive overproduction of surfactin enhances the invasive
      growth and the in vitro antagonistic activity of the mutant strain. Both
      properties are known to play an important role in the biocontrol of plant
      diseases. Plipastatin operon disruption increases the surfactin productivity of
      mutant strains. These mutants are interesting for use in continuous bioprocesses
      for surfactin production or in bioremediation.

PMID- 20148997
TI  - Methanogenic population dynamics during semi-continuous biogas fermentation and
      acidification by overloading.
AB  - AIMS: This study was to investigate the methanogenic community in a biogas
      reactor from start-up to acidification conditions. Furthermore, reliability and
      accuracy of the applied quantitative real-time PCR method (Q-PCR) was briefly
      evaluated. METHODS AND RESULTS: A mesophilic (37 degrees C), maize silage fed,
      continuously stirred tank reactor was surveyed. It was operated semi-continuously
      with increasing daily organic loading rates (OLRs) to reach acidification. Gas
      production and organic acid composition were measured. Methanogenic community
      structure was determined by 16S rDNA-based Q-PCR to estimate the abundance of key
      methanogenic micro-organisms. 16S rDNA of hydrogenotrophic Methanobacteriales was
      most abundant at OLRs of >or=3.7 g dry organic matter (DOM) l(-1) day(-1). By
      contrast, that of aceticlastic Methanosaetaceae predominated at lower OLRs but
      disappeared at OLRs of >or=4.1 g DOM l(-1) day(-1). At the same OLR, the
      propionate concentration increased dramatically indicating the acidification of
      the digester. Application of internal standards to examine Q-PCR's accuracy
      revealed that the detected amount of 16S rDNA may vary within one log cycle.
      CONCLUSIONS: These results suggest that the absence of Methanosaetaceae might be
      taken as biological indicator for process' instability. Inhibitory effects on Q
      PCR analyses could not be determined based on the spiking experiments.
      SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, reactors' microbiology was
      observed over time using Q-PCR. Insights into the abundance of different
      methanogens might be used to improve the performance of biogas reactors.

PMID- 20148998
TI  - Isolation of novel mycobacteria contaminating an aquarium fish tank in a Japanese
      university hospital.
AB  - AIMS: To better understand nontuberculous mycobacteria (NTM) contamination in a
      hospital setting, six freshwater fish gut homogenates and water in an aquarium
      fish tank placed on the reception counter of a nursing station were cultured for
      mycobacteria. METHODS AND RESULTS: By direct sequencing of 16s rRNA, rpoB and
      hsp65, scotochromogenic and nonchromogenic Mycobacterium szulgai isolates
      containing hsp65 type II (GenBank accession nos. FJ384762 and FJ384764,
      respectively), Mycobacterium gordonae isolates containing rpoB clusters B and E
      (GenBank accession no. FJ384766), and Mycobacterium kansasii isolates containing
      hsp65 type VI were collected from the gut homogenates and water from the fish
      tank. However, no isolates were obtained from the tap water used to refill the
      fish tank. A randomly amplified polymorphic DNA (RAPD) analysis using a 10-mer
      primer (5'-TGGTCGCGGC) showed that some NTM from the fish tank water were
      identical to those obtained from the gut homogenates. CONCLUSIONS: Fish and water
      in the tank were contaminated by the novel NTM. SIGNIFICANCE AND IMPACT OF THE
      STUDY: These findings could help to elucidate infection routes and contamination
      sources of novel NTM from water sources.

PMID- 20148999
TI  - Bartonellosis, an increasingly recognized zoonosis.
AB  - Cat scratch disease is the most common zoonotic infection caused by Bartonella
      bacteria. Among the many mammals infected with Bartonella spp., cats represent a
      large reservoir for human infection, as they are the main reservoir for
      Bartonella henselae, Bartonella clarridgeiae and Bartonella koehlerae. Bartonella
      spp. are vector-borne bacteria, and transmission of B. henselae by cat fleas
      occurs mainly through infected flea faeces, although new potential vectors (ticks
      and biting flies) have been identified. Dogs are also infected with various
      Bartonella species and share with humans many of the clinical signs induced by
      these infections. Although the role of dogs as source of human infection is not
      yet clearly established, they represent epidemiological sentinels for human
      exposure. Present knowledge on the aetiology, clinical features and
      epidemiological characteristics of bartonellosis is presented.

PMID- 20149000
TI  - Ethanol synthesis from glycerol by Escherichia coli redox mutants expressing adhE
      from Leuconostoc mesenteroides.
AB  - AIMS: Analysis of the physiology and metabolism of Escherichia coli arcA and creC
      mutants expressing a bifunctional alcohol-acetaldehyde dehydrogenase from
      Leuconostoc mesenteroides growing on glycerol under oxygen-restricted conditions.
      The effect of an ldhA mutation and different growth medium modifications was also
      assessed. METHODS AND RESULTS: Expression of adhE in E. coli CT1061 [arcA
      creC(Con)] resulted in a 1.4-fold enhancement in ethanol synthesis. Significant
      amounts of lactate were produced during micro-oxic cultures and strain CT1061LE,
      in which fermentative lactate dehydrogenase was deleted, produced up to 6.5 +/-
      0.3 g l(-1) ethanol in 48 h. Escherichia coli CT1061LE derivatives resistant to
      >25 g l(-1) ethanol were obtained by metabolic evolution. Pyruvate and
      acetaldehyde addition significantly increased both biomass and ethanol
      concentrations, probably by overcoming acetyl-coenzyme A (CoA) shortage. Yeast
      extract also promoted growth and ethanol synthesis, and this positive effect was
      mainly attributable to its vitamin content. Two-stage bioreactor cultures were
      conducted in a minimal medium containing 100 microg l(-1) calcium d-pantothenate
      to evaluate oxic acetyl-CoA synthesis followed by a switch into fermentative
      conditions. Ethanol reached 15.4 +/- 0.9 g l(-1) with a volumetric productivity
      of 0.34 +/- 0.02 g l(-1) h(-1). CONCLUSIONS: Escherichia coli responded to adhE
      over-expression by funnelling carbon and reducing equivalents into a highly
      reduced metabolite, ethanol. Acetyl-CoA played a key role in micro-oxic ethanol
      synthesis and growth. SIGNIFICANCE AND IMPACT OF THE STUDY: Insight into the
      micro-oxic metabolism of E. coli growing on glycerol is essential for the
      development of efficient industrial processes for reduced biochemicals production
      from this substrate, with special relevance to biofuels synthesis.

PMID- 20149001
TI  - How to do it: repair of anomalous left coronary artery from pulmonary artery
      (ALCAPA) with coronary button transfer and Lecompte maneuver.
AB  - An alternative technique of coronary button transfer and Lecompte maneuver for
      anomalous left coronary artery (ALCAPA) arising from left lateral pulmonary sinus
      is described. This technique was used by us successfully in four patients aged 6
      months to 3.5 years, weighing from 4.7 to 16 kg. The importance of trapdoor
      technique and Lecompte maneuver is discussed.

PMID- 20149002
TI  - Papillary fibroelastoma: insight to a primary cardiac valve tumor.
AB  - Papillary fibroelastomas are rare benign cardiac tumors. Although they have
      minimal hemodynamic effects, their propensity for embolization can result in
      serious morbidity. The pathophysiology and management of these tumors is the
      subject of this review.

PMID- 20149003
TI  - Late reoperations after repair of acute type A aortic dissection.
AB  - BACKGROUND: Regarding surgical interventions for type A acute aortic dissection
      (AAD), it is currently unclear if an initial, less invasive approach followed by
      later reoperations is safer than an extended approach aimed at preventing future
      reinterventions. We retrospectively reviewed our surgical cases to clarify the
      safety of late reoperation after repair of acute AAD. METHODS: Since 2004, 17
      patients (eight female; mean age: 64.1 +/- 9.3 years) of all 115 AAD cases in our
      institute underwent reoperations after initial repair of acute AAD, and operative
      factors were evaluated. RESULTS: Anastomotic pseudoaneurysms were the main reason
      for reoperation; one distal, seven proximal, and two both. Seven patients
      required surgical reintervention because of aneurysmal dilatation of the
      remaining aorta. The duration between the initial and late operations was 6.4 +/-
      5.1 years in the anastomotic pseudoaneurysm group and 4.6 +/- 4.5 years in the
      recurrence group. In the anastomotic pseudoaneurysm group, there were three root
      replacements, four resuspensions of the aortic valve, and two aortic valve
      replacements. Six patients required replacement of the aortic arch. Total arch
      replacement was the most frequent operation in the recurrence group. Three
      patients who required sternum reentries underwent concomitant right thoracotomies
      to dissect adhesions between the sternum and the aneurysm. There were no
      mortalities. CONCLUSIONS: Although most cases required extended procedures for
      late reoperation after repair of acute AAD, reoperations can be performed safely
      by careful choice of appropriate operative methods and strategies. Our data
      suggest that ascending aortic replacement is an effective initial procedure for
      patients with acute AAD.

PMID- 20149004
TI  - Novel approach to the treatment of distal malperfusion secondary to ascending
      aortic dissection.
AB  - Acute Type A dissection is a surgical emergency. The presence of visceral and
      extremity malperfusion syndromes increases perioperative mortality twofold. On
      occasion, significant malperfusion may best be addressed in a staged fashion with
      preliminary attention to specific vascular beds with delayed repair of the
      dissection itself. We present a subacute Type A dissection associated with
      malperfusion of multiple vascular beds (mesenteric, renal, and iliofemoral)
      managed with a complication-specific approach utilizing endovascular
      thoracoabdominal aortic repair prior to ascending repair.

PMID- 20149005
TI  - Mycotic aneurysm of the descending thoracic aorta caused by Haemophilus
      influenzae.
AB  - A 59-year-old man presented with a three-month history of back pain, and enhanced
      computed tomography demonstrated an acutely expanding aneurysm of the descending
      thoracic aorta with slight erosion of the corresponding vertebrae. Because of
      suspected infectious or inflammatory etiology, he was managed with a combination
      of emergency aortic repair using prosthetic graft with omental flap and
      antibiotic chemotherapy. Haemophilus influenzae was identified from perioperative
      specimens and the postoperative course was uneventful.

PMID- 20149006
TI  - Band occlusion of the atrial appendage.
AB  - OBJECTIVES: A new device has been developed for occlusion of the left atrial
      appendage (LAA). Previous investigations have been in the canine model. The
      canine atrial appendage does not vary in size and shape as much as the human. The
      goal of this study was to investigate band occlusion of right atrial appendages
      in the pig model, which are more broad based. METHODS: The right atrial
      appendages of six pigs were approached through a right thoracotomy. An expandable
      polyester fabric-covered silicone band was placed on the appendage. The animals
      were evaluated at the time of band placement with fluoroscopy, contrast
      injection, and in three animals, echocardiography. After one week, the animals
      were again evaluated with fluoroscopy. The animals were sacrificed at 12 weeks.
      RESULTS: Bands were placed without complication at the base of all six
      appendages. All appendages were effectively occluded and all bands remained at
      the appendage base. The healed atrial surface was consistently smooth and devoid
      of thrombus. CONCLUSIONS: Occlusion of a broad-based appendage as seen with human
      LAA is feasible with this novel band technique.

PMID- 20149007
TI  - Right ventricular thromboembolism associated with severe aortic stenosis.

PMID- 20149008
TI  - Poststernotomy pseudoaneurysm of the internal mammary artery: endovascular
      treatment.

PMID- 20149009
TI  - Pulmonary embolectomy: recommendation for early surgical intervention.
AB  - BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening disease which
      often results in death if not diagnosed early and treated aggressively. Despite
      all efforts at improving outcomes, there is no consensus on the management of
      acute severe PE. METHODS: From May 2000 to June 2009, 16 consecutive patients
      underwent surgical pulmonary embolectomy at our institution. Mean age was 45 +/-
      17 years (range, 14 to 76) with nine (56%) males and seven (43%) females.
      Preoperatively, all cases were classified as massive PE; seven (43%) patients
      were in hemodynamic collapse and emergently underwent operation while receiving
      cardiopulmonary resuscitation. RESULTS: There were nine (56%) urgent/emergent and
      seven (44%) salvage patients undergoing surgical pulmonary embolectomy. Of nine
      nonsalvage patients, seven (77%) patients presented with moderate to severe right
      ventricular (RV) dilation/dysfunction. Mean cardiopulmonary bypass time was 43 +/
      41 minutes (range, 9 to 161). Mean follow-up duration was 48 +/- 38 months
      (range: 0.3 to 109), with seven in-hospital deaths (43%): mortality was 11% (1/9)
      in emergent operations and 85% (6/7) in salvage operations. CONCLUSIONS: Surgical
      pulmonary embolectomy should be considered early in the management of
      hemodynamically stable patients with PE who show evidence of RV dilation and/or
      failure, as it is associated with satisfactory outcomes. Conversely, pulmonary
      embolectomy has dismal results under salvage conditions. Revision of current
      guidelines for the surgical management of this condition may be warranted.

PMID- 20149010
TI  - Gastrointestinal complications following cardiac surgery: a comprehensive review.
AB  - INTRODUCTION: Gastrointestinal (GI) complications following cardiac surgery are
      associated with a high morbidity and mortality, prolonged hospital stay and
      increased cost of hospitalization. METHODS: A literature search was carried out
      using Medline for articles published in the past 30 years. Prospective and
      retrospective papers that dealt with coronary artery bypass grafting (CABG),
      CABG/valve operations were selected and those that dealt with thoracic and
      transplant complications were excluded. RESULTS: We reviewed 151,652 patients
      reported over the past 30 years; GI complications occurred on average after 1.21%
      of cardiac operations and had an associated mortality of 34.1%. The most common
      risk factors identified include age greater than 70 years, low cardiac output,
      peripheral vascular disease, reoperative surgery, chronic renal insufficiency,
      increased number of blood transfusions, prolonged cardiopulmonary bypass time,
      arrhythmias, and use of an intraaortic balloon pump. A critical examination of
      the available literature revealed multifactorial etiologies (often related to
      hypoperfusion) leading to GI complications. Delayed diagnosis was associated with
      poor outcomes. CONCLUSION: GI complications are rare events, but early diagnosis
      is essential. Unfortunately few of the risk factors we have defined are specific
      and are often indicators of ill patients. A low threshold to initiate laboratory
      evaluation and/or imaging studies should be employed if a patient shows signs of
      deviating from the normal course following cardiac surgery.

PMID- 20149011
TI  - What's new in cardiac cell therapy? Allogeneic bone marrow stromal cells as
      "universal donor cells".
AB  - Cardiac cell therapies offer distinct and exciting advantages over current
      treatments to prevent postinfarction heart failure because they can reverse
      ventricular remodeling and improve function, but only if the implanted stem cells
      contribute biological functions and achieve prolonged engraftment within the
      hostile environment of the damaged heart. Unfortunately, function is diminished
      in autologous stem cells isolated from older patients and those with
      comorbidities, and so clinical trials testing the implantation of healthy,
      allogeneic bone marrow-derived stromal cells (MSCs) isolated from young donors
      are currently underway. MSCs are unique because, in addition to exerting
      paracrine effects that restore blood flow and recruit endogenous stem cells to
      the infarct, they exhibit immune-modulating properties in culture that-if
      retained after allogeneic implantation-imply the cells may escape immune
      recognition within the heart. At present, the scope of MSC immune modulation
      after implantation is unclear.

PMID- 20149012
TI  - Right ventricular perforation due to migration of a ventricular lead.

PMID- 20149013
TI  - Resection of a mobile cardiac metastatic melanoma.

PMID- 20149014
TI  - Surgical technique of removal of inferior vena cava leiomyosarcoma extending into
      the right atrium without deep hypothermic circulatory arrest.
AB  - BACKGROUND: Leiomyosarcoma of the inferior vena cava is a rare tumor with
      potential for significant morbidity and mortality. Surgical extirpiration remains
      the optimal treatment choice. A case of caval leiomyosarcoma with right atrial
      extension is presented with management techniques and literature review. METHODS:
      A 54 year old woman with constitutional symptoms was found to have advanced caval
      leiomyosarcoma with atrial extension. Surgical excision was performed without
      deep hypothermic circulatory arrest (DHCA), including right nephrectomy,
      adrenalectomy, and en-bloc resection of the vena cava along with Gore-Tex
      interposition graft. RESULTS: There were no operative complications. The patient
      was extubated on postoperative day one. Renal function remained normal. Final
      pathology was high grade leiomyosarcoma. Margins were negative. The patient is
      well at latest follow up. CONCLUSION: Resection of extensive caval leiomyosarcoma
      allows the best chance of cure and is possible without DHCA. Perioperative
      planning and coordination and adherence to oncologic techniques is critical.

PMID- 20149015
TI  - Incomplete isolation of the left innominate artery in a patient with right aortic
      arch and double outlet right ventricle.
AB  - Isolation of the left innominate artery (IA) with right aortic arch is a rare
      congenital anomaly in which the IA loses its connection to the aorta and is
      connected to the pulmonary artery via a left ductus arteriosus. Here, we report a
      case of a 9-month-old girl with incomplete isolation of the IA and double outlet
      right ventricle. Along with repair of the intracardiac anomaly, the IA was
      reimplanted to aortic arch to ensure adequate blood flow from the aorta.

PMID- 20149016
TI  - Medial necrosis in aortic root aneurysm after repair of tetralogy of Fallot.
AB  - Aneurysmal dilatation of the aortic root occurs in some patients with tetralogy
      of Fallot (TOF) late after repair. It can lead to aortic valve insufficiency and
      rarely to aortic rupture or dissection. Aortic valve or aortic surgery is rarely
      performed in this group of patients. We present a case of aneurysmal dilatation
      of the ascending aorta treated with aortic valve sparing root replacement 43
      years after the TOF repair. Histological examination of the aortic wall revealed
      medial necrosis. The implications of those finding and the timing of surgery are
      discussed.

PMID- 20149017
TI  - Penetrating nail injury to the right ventricle associated with thrombus
      formation.

PMID- 20149018
TI  - Putting information back into biological communication.
AB  - At the heart of many debates on communication is the concept of information.
      There is an intuitive sense in which communication implies the transfer of some
      kind of information, probably the reason why information is an essential
      ingredient in most definitions of communication. However, information has also
      been an endless source of misunderstandings, and recent accounts have proposed
      that information should be dropped from a formal definition of communication. In
      this article, we re-evaluate the merits and the internal logic of information
      based vs. information-free approaches and conclude that information-free
      approaches are conceptually incomplete and operationally hindered. Instead, we
      propose a functional notion of information that follows logically from previous
      adaptationist accounts. The ensuing definition of communication provides a wider,
      more inclusive theoretical scope that reflects more accurately the evolutionary
      scenario shaping animal signals. Additionally, it is a definition better equipped
      to deal with the extraordinary diversity of animal signals, facilitates the
      distinction of honest and deceptive signals at a proximate level and accommodates
      a number of conceptual and practical issues (e.g. redundancy, alerting
      components) that are lost when we fail to acknowledge the informative content of
      animal signals.

PMID- 20149019
TI  - Heritability of resistance to oxidative stress in early life.
AB  - Oxidative stress has recently been suggested to play an important role in life
      history evolution, but little is known about natural variation and heritability
      of this physiological trait. Here, we explore phenotypic variation in resistance
      to oxidative stress of cross-fostered yellow-legged gull (Larus cachinnans)
      chicks. Resistance to oxidative stress was not related to plasma antioxidants at
      hatching, which are mostly derived from maternal investment into eggs. Common
      environmental effects on phenotypic variation in resistance to oxidative stress
      were not significant. Heritability was relatively low and nonsignificant in
      hatchlings, but interestingly, the chicks of age 8 days showed high and
      significant heritability (h(2) = 0.59). Our results suggest that resistance to
      oxidative stress is determined mainly by the genotype as chicks grow. Further
      work is required to explore the genetic role of oxidative stress in life-history
      evolution.

PMID- 20149020
TI  - The genetic basis of early-life morphological traits and their relation to
      alternative male reproductive tactics in Atlantic salmon.
AB  - Although heritability estimates for traits potentially under natural selection
      are increasingly being reported, their estimation remains a challenge if we are
      to understand the patterns of adaptive phenotypic change in nature. Given the
      potentially important role of selection on the early life phenotype, and thereby
      on future life history events in many fish species, we conducted a common garden
      experiment, using the Atlantic salmon (Salmo salar L.), with two major aims. The
      first objective is to determine how the site of origin, the paternal sexual
      tactic and additive genetic effects influence phenotypic variation of several
      morphological traits at hatching and emergence. The second aim is to test whether
      a link exists between phenotypic characteristics early in life and the incidence
      of male alternative tactics later in life. We found no evidence of a site or
      paternal effect on any morphological trait at hatching or emergence, suggesting
      that the spatial phenotypic differences observed in the natural river system from
      which these fish originated are mainly environmentally driven. However, we do
      find significant heritabilities and maternal effects for several traits,
      including body size. No direct evidence was found correlating the incidence of
      precocious maturation with early life characteristics. We suggest that under good
      growing conditions, body size and other traits at early developmental stages are
      not reliable cues for the surpassing of the threshold values associated with male
      sexual development.

PMID- 20149021
TI  - Population differences in behaviour are explained by shared within-population
      trait correlations.
AB  - Correlations in behavioural traits across time, situation and ecological context
      (i.e. 'behavioural syndromes' or 'personality') have been documented for a
      variety of behaviours, and in diverse taxa. Perhaps the most controversial
      inference from the behavioural syndromes literature is that correlated behaviour
      may act as an evolutionary constraint and evolutionary change in one's behaviour
      may necessarily involve shifts in others. We test the two predictions of this
      hypothesis using comparative data from eighteen populations of the socially
      polymorphic spider, Anelosimus studiosus (Araneae, Theriidae). First, we ask
      whether geographically distant populations share a common syndrome. Second, we
      test whether population differences in behaviour are correlated similarly to
      within-population trait correlations. Our results reveal that populations
      separated by as much as 36 degrees latitude shared similar syndromes.
      Furthermore, population differences in behaviour were correlated in the same
      manner as within-population trait correlations. That is, population divergence
      tended to be along the same axes as within-population covariance. Together, these
      results suggest a lack of evolutionary independence in the syndrome's constituent
      traits.

PMID- 20149022
TI  - The need for archiving data in evolutionary biology.

PMID- 20149023
TI  - Transgenerational memory effect of ageing in Drosophila.
AB  - Children born to older parents tend to have lower intelligence and are at higher
      risk for disorders such as schizophrenia and autism. Such observations of ageing
      damage being passed on from parents to offspring are not often considered within
      the evolutionary theory of ageing. Here, we show the 25% memory impairment in
      Drosophila melanogaster offspring solely dependent on the age of the parents and
      also passed on to the F2 generation. Furthermore, this parental age effect was
      not attributed to a generalized reduction in condition of the offspring but was
      specific to short-term memory. We also provide evidence implicating oxidative
      stress as a causal factor by showing that lines selected for resistance to
      oxidative stress did not display a memory impairment in offspring of old parents.
      The identification of the parental age-related memory impairment in a model
      system should stimulate integration between mechanistic studies of age-related
      mortality risk and functional studies of parental age effects on the fitness of
      future generations.

PMID- 20149024
TI  - Habitat-specific population structure in native western flower thrips
      Frankliniella occidentalis (Insecta, Thysanoptera).
AB  - Invasions by pest organisms are among the main challenges for sustainable crop
      protection. They pose a serious threat to crop production by introducing a highly
      unpredictable element to existing crop protection strategies. The western flower
      thrips Frankliniella occidentalis (Insecta, Thysanoptera) managed to invade
      ornamental greenhouses worldwide within < 25 years. To shed light on possible
      genetic and/or ecological factors that may have been responsible for this
      invasion success, we studied the population genetic structure of western flower
      thrips in its native range in western North America. Analysis of nucleotide
      sequence variation and variation at microsatellite loci revealed the existence of
      two habitat-specific phylogenetic lineages (ecotypes) with allopatric
      distribution. One lineage is associated with hot/dry climates, the second lineage
      is restricted to cool/moist climates. We speculate that the ecological niche
      segregation found in this study may be among the key factors determining the
      invasion potential of western flower thrips.

PMID- 20149025
TI  - Adaptation of experimental yeast populations to stressful conditions in relation
      to population size.
AB  - The purpose of this experiment was to find out how a population becomes adapted
      to extremely stressful conditions as its environment deteriorates. We created a
      deteriorating environment for experimental selection lines of yeast by a stepwise
      increase in the concentration of salt in the growth medium. After each step, we
      tested the ability of the lines to grow at a high concentration of salt near the
      lethal limit for the ancestral strain. We found that mutations enhancing growth
      in this highly stressful environment began to spread at intermediate salt
      concentrations. The degree of enhancement was related to effective population
      size by a power law with a small exponent. The effect size of these mutations
      also increased with the population size in a similar fashion. From these results,
      we interpret adaptation to lethal stress as an indirect response to selection for
      resistance to previous lower levels of stress in a deteriorating environment.
      This suggests that the pattern of genetic correlation between successively higher
      levels of stress is an important factor in facilitating evolutionary rescue.

PMID- 20149026
TI  - Ontogenetic and spatial variation in size-selective mortality of a marine fish.
AB  - Although body size can affect individual fitness, ontogenetic and spatial
      variation in the ecology of an organism may determine the relative advantages of
      size and growth. During an 8-year field study in the Bahamas, we examined
      selective mortality on size and growth throughout the entire reef-associated life
      phase of a common coral-reef fish, Stegastes partitus (the bicolour damselfish).
      On average, faster-growing juveniles experienced greater mortality, though as
      adults, larger individuals had higher survival. Comparing patterns of selection
      observed at four separate populations revealed that greater population density
      was associated with stronger selection for larger adult size. Large adults may be
      favoured because they are superior competitors and less susceptible to gape
      limited predators. Laboratory experiments suggested that selective mortality of
      fast-growing juveniles was likely because of risk-prone foraging behaviour. These
      patterns suggest that variation in ecological interactions may lead to complex
      patterns of lifetime selection on body size.

PMID- 20149027
TI  - The normal and abnormal owl monkey (Aotus sp.) heart: looking at cardiomyopathy
      changes with echocardiography and electrocardiography.
AB  - BACKGROUND: Cardiovascular disease, especially cardiomyopathy, was the major
      cause of death among owl monkeys (Aotus sp.) at a major colony and threatened
      colony sustainability. For this study, echocardiography (echo) and
      electrocardiography (ECG) normal values were established, and cardiomyopathy
      animals identified. METHODS: Forty-eight owl monkeys were studied, 30 older than
      10 years of age ('aged') and 8 of age 5 years ('young'). Eight aged owl monkeys
      had cardiomyopathy. RESULTS AND CONCLUSIONS: Aged Aotus had increased left
      ventricular posterior wall thickness over young animals. Left ventricular
      diameter and ejection fraction appeared to be the best identifying measurements
      for cardiomyopathy. There were no differences in the ECG.

PMID- 20149028
TI  - Modulation of endothelial and neuronal nitric oxide synthases during learning of
      an operant conditioning task.
AB  - Nitric oxide (NO) promotes plasticity and it is essential for learning, the NO
      synthases involved in these events are the endothelial NO synthase (eNOS) and
      neuronal NO synthase (nNOS) isoforms. The aim of this study was to study
      transcription, protein expression and enzymatic activity of eNOS and nNOS in the
      prefrontal cortex and the hippocampus during learning an operant conditioning
      task. Animals were considered incompletely trained (IT) when performed between
      50% and 65% of responses, whereas animals were considered trained when reached
      100% of responses with a latency time lower than 5 s. Following training session
      animals were killed and we quantified mRNA levels by Real Time RT-PCR, protein
      expression by western blot and enzymatic activity. eNOS and nNOS mRNA levels were
      only incremented in IT group. On the contrary, protein expression of both
      isoforms were augmented during all learning process. Moreover, we also found that
      eNOS and nNOS synthase activity were incremented in IT group and in trained
      group. Here, we showed that during learning there is a differential regulation of
      eNOS and nNOS in the prefrontal cortex and hippocampus and that NO could be
      acting as a promoter of plasticity.

PMID- 20149029
TI  - Effect of human chorionic gonadotrophin on in vitro contractions of stimulated
      detrusor muscle strips of female rats.
AB  - AIMS: We studied the effect of human chorionic gonadotrophin (hCG) on the in
      vitro detrusor muscle contractions in female rats. METHODS: Two adjacent detrusor
      muscle strips from the bladder dome of 18 female Wistar rats (230-250 gm) were
      mounted in an organ bath for the recording of isometric tension. Carbachol (10(
      9)-10(-3) M), alpha,beta methylene adenosine 5'-triphosphate (ATP) (10(-9)-10(-3)
      M) and potassium chloride (KCl) (10(-4)-10(-3) M) were applied (n = 6 x 3
      groups). Concentration-response curves, before and after the addition of hCG (100
      iu/mL) or oxybutynin (10(-5) M) to either muscle strip, were compared. RESULTS:
      All curves were displaced to the right by hCG in a concentration-dependent manner
      with significant inhibition of contractions induced by carbachol (P < 0.001) and
      KCl (P = 0.016) but not those induced by alpha,beta-methylene ATP (P = 0.4).
      Estimated order of potency of inhibition was carbachol>KCl>alpha,beta-methylene
      ATP. The overall inhibitory effect of hCG was significantly less than oxybutynin
      (P < 0.001). CONCLUSIONS: hCG significantly inhibited in vitro detrusor
      contractions induced by depolarization (KCl) and cholinergic (carbachol) but not
      purinergic (alpha,beta-methylene ATP) stimulation in a dose-dependent manner in
      female rats.

PMID- 20149030
TI  - Microarray profile of micro-ribonucleic acid in tumor tissue from cervical
      squamous cell carcinoma without human papillomavirus.
AB  - AIMS: Micro-ribonucleic acid (miRNA) are noncoding RNA molecules of 21 to 24 nt
      that regulate the expression of target genes in a post-transcriptional manner.
      Evidence indicates that miRNA play essential roles in embryogenesis, cell
      differentiation and pathogenesis of human diseases. This study describes a
      comparison between the microRNA profile of human-papillomavirus-negative cervical
      squamous cell carcinoma patients and controls, in order to develop further
      understanding of the pathogenesis of cervical squamous cell carcinomas. METHODS:
      MiRNA were isolated from tumor tissues of five human-papillomavirus-negative
      cervical squamous cell carcinoma patients and five healthy controls in order to
      perform miRNA microarray chip analysis. The chip results were then confirmed by
      northern blot analysis. RESULTS: A total of 27 miRNA differentially expressed
      between the squamous cell carcinoma patients and the healthy controls were
      identified. CONCLUSION: This work indicates that these miRNA may be potential
      diagnosis biomarkers and probable factors involved in the pathogenesis of
      cervical squamous cell carcinomas.

PMID- 20149031
TI  - Uterine artery flow velocity waveforms during uterine contractions: differences
      between oxytocin-induced contractions and spontaneous labor contractions.
AB  - AIM: To clarify the effects on uterine arterial flow velocity waveforms of
      uterine contractions following oxytocin infusion and during spontaneous labor.
      METHODS: Uterine arterial flow velocity waveforms were obtained by pulsed Doppler
      methods from 22 women during an oxytocin challenge test (OCT), 26 women during
      oxytocin-induced labor, and 40 women during spontaneous labor. Mean resistance
      index (RI) for bilateral arteries was used for analyses. After the onset of
      labor, flow velocity waveforms were assessed according to cervical dilatation.
      During OCT, Doppler flow velocimetry was performed when three uterine
      contractions occurred per 10-min period. RESULTS: RI values did not differ
      significantly between induced and spontaneous labor during relaxations at any
      level of cervical dilatation. However, during contractions, RI was significantly
      higher for induced labor than for spontaneous labor. Absence or reversal of flow
      was more frequent in the OCT group than in the induced labor group (P < 0.0001).
      However, no significant differences were found between spontaneous and induced
      labor groups. CONCLUSION: Interactions between the contracting uterine body and
      the relaxing lower segment in oxytocin-induced labor might be associated with
      differences in uterine arterial flow during contraction between oxytocin-induced
      and spontaneous labor. However, changes in the intensity of uterine contractions
      during labor progression might differ between oxytocin-induced and spontaneous
      labor.

PMID- 20149032
TI  - Maternal plasma soluble fms-like tyrosine kinase-1 and placental growth factor
      levels as biochemical markers of gestational hypertension for Malaysian mothers.
AB  - AIMS: To establish baseline levels of maternal plasma soluble fms-like tyrosine
      kinase-1 (sFlt-1) and placental growth factor (PlGF) among normotensive Malaysian
      mothers and to compare the marker levels between normotensives and mothers with
      gestational hypertension (GH). METHODS: Plasma sFlt-1 and PlGF were measured by
      enzyme-linked immunosorbent assay in an unmatched, case-control study. The
      results were subjected to normality testing and analyzed by Mann-Whitney U-tests.
      RESULTS: Among normotensive mothers, both sFlt-1and PlGF showed a general
      increase in levels from the 24th to 32nd weeks of pregnancy. PlGF levels in
      normotensive mothers with gestational diabetes mellitus were reduced compared to
      those without the disease, while levels of sFlt-1 were elevated. Mothers with GH
      had reduced levels of PlGF with increased levels of sFlt-1 when compared to
      normotensive mothers. Among the normotensive mothers followed up until delivery,
      the inversed pattern of reduced PlGF and increased sFlt-1 marker levels was found
      in 40% of those who developed GH later in pregnancy. CONCLUSIONS: Plasma levels
      of sFlt-1and PlGF in normotensive mothers may be influenced by gestational
      diabetes mellitus and GH. GH mothers show an inversed pattern of marker levels
      compared to normotensive mothers.

PMID- 20149033
TI  - Does breastfeeding induce spontaneous abortion?
AB  - AIM: To verify the hypothesis that even if breastfeeding is continued during
      pregnancy, there are no harmful effects on pregnancy. METHODS: The outcomes of
      pregnancies in mothers who continued breastfeeding during pregnancy were studied.
      One hundred and ten pregnant women were recruited who had one full-term baby, no
      experience of premature birth or abortion, and who continued to breastfeed at
      diagnosis of pregnancy. Age and pregnancy history matched 774 pregnant women were
      selected as a control group. All of the control women stopped breastfeeding at
      least 3 months before becoming pregnant. We reviewed the outcome of each
      pregnancy retrospectively from patient records. Statistical analysis was
      conducted using the chi(2) test. RESULTS: Eight of 110 pregnancies (7.3%)
      resulted in spontaneous abortion in the breastfeeding group, and 65 of 774
      pregnancies (8.4%) in the control group. There were no statistically significant
      differences between the two groups (P > 0.05). CONCLUSION: Even if the mother is
      pregnant, breastfeeding should be continued until natural weaning occurs. Further
      study is required to conclude safety of breastfeeding and premature birth.

PMID- 20149034
TI  - Oncostatin M as a target biological molecule of preeclampsia.
AB  - AIM: Given the presence of the cytokinetic effects of Oncostatin M (OSM), we
      hypothesized that placental expression of OSM and serum OSM levels are elevated
      in preeclampsia. To verify this hypothesis, we determined the expression of OSM
      in placenta and levels of OSM in plasma form women with preeclampsia and normal
      pregnant women. METHODS: Sixteen women with severe preeclampsia and 16 normal
      pregnancy women were studied. Placental tissues were immediately frozen and
      stored at -80 degrees C until extraction of total RNA. Total RNA was extracted
      and real-time quantitative PCR was carried out. Placental tissues fixed in 4%
      paraformaldehyde were reacted with antibodies against OSM. An independent
      pathologist who was blind to the origins of the samples reviewed these stained
      slides. The maternal serum and umbilical venous concentration of OSM were
      determined by commercially available ELISA analysis. RESULTS: The mRNA expression
      level of OSM in preeclamptic placenta was increased by 3.91 times which was
      significantly higher than those of the normal group (P = 0.028). OSM
      immunoreactivity was significantly higher in placentas of patients with
      preeclampsia than placentas from the normal group. The significantly greater OSM
      expressions were noted in cytotrophoblasts, syncytotrophoblasts and endothelium
      of preeclamptic placentas as compared to normal placentas (respectively, P =
      0.004, 0.001 and 0.04). OSM concentration of preeclamptic women's serum was
      significantly higher than that of normal women's plasma (P = 0.016). However, OSM
      level of umbilical venous serum was not significantly different between two
      groups (P = 0.243) CONCLUSION: OSM may play a biological marker for severe
      preeclampsia, and its action may be predominantly on the trophoblasts and
      endothelium of placenta villi in preeclampsia.

PMID- 20149035
TI  - A survey of the knowledge and attitudes of pregnant Thai women towards Down
      syndrome screening.
AB  - AIM: To determine the knowledge and attitudes of pregnant Thai women towards Down
      syndrome screening. METHODS: A total of 714 pregnant women were recruited
      attending antenatal clinics in Songklanagarind Hospital from February through
      June 2007. Their knowledge and attitudes concerning Down syndrome screening were
      evaluated through self-administered questionnaires. The data were analyzed using
      SPSS version 12.0. RESULTS: The mean age of the respondents was 29.9 +/- 6.4
      years. Regarding their knowledge of Down syndrome and its screening test, the
      mean scores were 43.6% and 20.6%, respectively. Most pregnant women (77.6%) had a
      positive attitude to Down syndrome screening. In addition, 92.2% of cases would
      accept a Down syndrome screening test. Multivariate logistic regression analysis
      showed that levels of education and types of health insurance were factors
      associated with knowledge of Down syndrome screening. Maternal age was the only
      factor affecting attitudes. CONCLUSION: Most pregnant women had inadequate
      knowledge of Down syndrome and the screening test. However, they did have a
      positive attitude and were willing to accept the test. Providing knowledge on
      Down syndrome and the screening test for pregnant women should be implemented in
      our antenatal care services and community.

PMID- 20149036
TI  - Clinical features of fetal growth restriction complicated later by preeclampsia.
AB  - OBJECTIVE: To assess the maternal and perinatal outcome of preeclampsia with
      fetal growth restriction (FGR) and to assess the risk factors of FGR complicated
      later by preeclampsia. SUBJECTS AND METHODS: A cohort of women with preeclampsia
      and/or FGR (n = 306) were retrospectively reviewed. First, the maternal and
      perinatal outcome were compared between preeclampsia with FGR (n = 37) and
      preeclampsia without FGR (n = 96). Second, the clinical findings of FGR followed
      later by preeclampsia (n = 24) were compared to FGR without preeclampsia (n =
      149). RESULTS: The incidence of severe hypertension and critical maternal
      complications in women with preeclampsia with FGR was significantly higher than
      in those with preeclampsia without FGR. In women diagnosed with FGR, 13.8%
      (24/173) developed preeclampsia later. In this group, FGR was diagnosed at 28.8
      gestational weeks, which was then complicated by preeclampsia at a mean of 32.6
      gestational weeks, and delivered at 33.3 gestational weeks. The diagnosis of FGR
      was earlier and the incidence of proteinuria at entry was more common in women
      with FGR complicated later by preeclampsia than in those with FGR without
      preeclampsia (45.8% vs 4.7%; P < 0.001). CONCLUSIONS: Preeclampsia with FGR is
      severe condition which can possibly adversely affect the maternal condition.
      About 15% of all mothers diagnosed with FGR developed preeclampsia afterwards;
      therefore, those with FGR are considered to be candidates for close monitoring
      for the clinical manifestation of preeclampsia, and those with early-onset FGR
      with proteinuria may represent a high-risk group for preeclampsia.

PMID- 20149037
TI  - Increased interaction between heat shock protein 27 and mitogen-activated protein
      kinase (p38 and extracellular signal-regulated kinase) in pre-eclamptic
      placentas.
AB  - AIMS: Heat shock protein 27 (Hsp27) is a well-known stress response protein that
      is characterized by its phosphorylative capacity. Hsp27 becomes phosphorylated in
      response to various stimuli through interaction with several different kinases.
      The purpose of this study was to evaluate the interaction between Hsp27 and
      mitogen-activated protein kinase (MAPK) (p38, extracellular signal-regulated
      kinase [ERK], and c-Jun N-terminal kinase) in the human placenta derived from
      patients with pre-eclampsia. METHODS: Western blot analysis was used to examine
      the levels of expression of Hsp27 and MAPK (p38, ERK, and c-Jun N-terminal
      kinase). Immunoprecipitation analysis was used to determine the interaction
      between Hsp27 and MAPK (p38 and ERK). RESULTS: Western blotting analysis and
      immunohistochemistry showed that the expression of Hsp27 and p-Hsp27 in the
      placental tissues of the pre-eclampsia group were significantly higher than that
      in the normal pregnancy group. Immunoprecipitation analysis showed that the
      interaction between Hsp27 and MAPK (p38 and ERK) was significantly increased in
      the pre-eclamptic placenta tissues. CONCLUSION: The interaction between Hsp27 and
      MAPK was increased, suggesting that phosphorylation of Hsp27 might be induced by
      p38 and ERK in placentas from patients with pre-eclampsia.

PMID- 20149038
TI  - Oral hydration therapy in oligohydramnios.
AB  - AIM: Oligohydramnios is a threatening condition to fetal health, for which some
      treatments are available, or are under evaluation. We aimed to assess the effect
      of acute oral hydration on maternal amniotic fluid index (AFI). METHODS: An
      randomized controlled trial was conducted on 44 pregnant women diagnosed by
      sonography to have oligohydramnios (2.1 < AFI < 6 cm). RESULTS: The mean AFI
      before intervention was 50.8 in the intervention group and 52.1 in the control
      group. After intervention, the mean AFI was 67.2 and 52.5 in the intervention and
      control groups, respectively, (P < 0.001, t-test = 3.827). The mean urinary
      specific gravity (USG) change was 13.4 after oral hydration in the intervention
      group and 1.68 in the control group (P < 0.001, t-test = 3.954). CONCLUSION:
      Acute oral hydration is a noninvasive, easily accessible and cheap intervention,
      and an effective way of increasing AFI.

PMID- 20149039
TI  - Midtrimester termination of pregnancy using gemeprost in combination with
      laminaria in women who have previously undergone cesarean section.
AB  - AIM: We aimed to assess the efficacy and safety of midtrimester termination of
      pregnancy using gemeprost in combination with laminaria in women who had
      previously undergone cesarean section and in women who had not. METHODS: Between
      January 1999 and December 2006, we carried out a retrospective study of
      termination of pregnancy at 12-21 weeks of gestation at the University of Tsukuba
      Hospital. Termination of pregnancy was carried out by three-step uterine cervical
      dilation using laminaria followed by vaginal administration of 1 mg gemeprost
      every 3 h for up to four doses over 24 h. RESULTS: A total of 173 women underwent
      midtrimester termination of pregnancy. The women were categorized into two
      groups: those who had previously undergone cesarean section (n = 26) (previous
      cesarean section group) and those who had not (n = 147) (control group). Seven
      women had undergone cesarean section at least twice. The gemeprost dose
      administered was 2.8 +/- 1.4 mg for the previous cesarean section group and 2.4
      +/- 1.6 mg for the control group (difference in doses not significant). Although
      abnormal vaginal bleeding (>500 mL) was more likely to occur in the previous
      cesarean section group than in the control group (odds ratio, 2.61; 95%
      confidence interval, 0.63-10.82), none of the woman required blood transfusion.
      Uterine rupture and failed abortion were not observed. CONCLUSION: The efficacy
      and safety of our laminaria-gemeprost protocol for termination of pregnancy
      during the midtrimester are similar for women who have previously undergone
      cesarean section and those who have not.

PMID- 20149040
TI  - Safety of cesarean myomectomy.
AB  - AIM: To examine the safety and appropriateness of uterine myomectomy during
      cesarean section. METHODS: We conducted a retrospective analysis of 97 patients
      who underwent myomectomy during cesarean section and 60 patients who had uterine
      myomas, but underwent cesarean section only, between January 2000 and December
      2007. Based on the patients' medical records, we conducted an analysis of the
      characteristics of the uterine myomas, hematologic changes that occurred between
      the preoperative and postoperative phases, complications, and length of hospital
      stay. RESULTS: Changes in hemoglobin values between the preoperative and
      postoperative phases, indicating the degree of intraoperative bleeding, were
      evaluated. There were no significant differences between the two groups (cesarean
      myomectomy group [1.2 +/- 1.2 g/dL] versus control group [1.1 +/- 1.3 g/dL]).
      There were no significant differences in the frequency of blood transfusion,
      incidence of postoperative fever, duration of surgery, and length of hospital
      stay between the two groups. In patients who received a blood transfusion
      intraoperatively, the increased amount was added to the hemoglobin changes
      between the preoperative and postoperative phases (adjusted value). The
      difference in the adjusted value of hemoglobin change did not reach statistical
      significance (cesarean myomectomy group [1.3 +/- 1.2 g/dL] versus control group
      [1.2 +/- 1.1 g/dL]). When the size of the uterine myoma exceeded 6 cm, the
      operative time was longer in the cesarean myomectomy group. CONCLUSION: Cesarean
      myomectomy is a safe surgical option with no significant complications if
      performed by an experienced practitioner.

PMID- 20149041
TI  - The prevalence of hereditary breast/ovarian cancer risk in patients with a
      history of breast or ovarian cancer in Japanese subjects.
AB  - AIM: Women at high risk for hereditary breast/ovarian cancer require specific
      management strategies for cancer prevention and early detection. The authors
      sought to determine the prevalence of family histories suggestive of a hereditary
      breast/ovarian cancer syndrome in patients with a personal history of breast or
      ovarian cancer in Japanese women. METHODS: Family history (first- and second
      degree relatives) data were collected by a self-administered questionnaire for
      women with a history of breast or ovarian cancer in six major cancer treating
      hospitals in Niigata prefecture, Japan. RESULTS: Data were obtained from 1463
      women: 626 women with a history of breast cancer, 289 women with a history of
      ovarian cancer and 548 women without a history of any cancer as controls. Women
      with a family history of breast and/or ovarian cancer had OR of breast cancer of
      2.3 (95% confidential interval [CI] 1.5-3.7) and ovarian cancer of 2.2 (95% CI
      1.3-3.8). The risk was higher when the proband was younger or when two or more
      relatives were affected. Among women with a history of breast or ovarian cancer,
      7.5% met the criteria for a 10% risk of a BRCA1 or BRCA2 mutation according to
      the Myriad model. CONCLUSION: Obtaining a detailed breast and ovarian cancer
      family history and the application of the Myriad model is useful for identifying
      women at an elevated genetic risk of breast and ovarian cancer. The estimation
      for the prevalence of hereditary breast/ovarian cancer syndrome has significant
      implications for a patient's management, as well as for the capacity for risk
      assessment and testing.

PMID- 20149042
TI  - Constitutive activation of signal transducer and activator of transcription 3 in
      epithelial ovarian carcinoma.
AB  - AIM: To investigate the expressions of signal transducer and activator of
      transcription 3 (Stat3) and tyrosine-activated Stat3 (p-Stat3) in epithelial
      ovarian carcinoma (EOC) and their relationships with clinical pathological
      parameters or prognosis. METHODS: Immunohistochemical methods were used to detect
      the expressions of Stat3 and p-Stat3 in EOC, benign ovarian tumors and normal
      ovarian tissues, after which an analysis of results with clinical pathological or
      prognosis was given. RESULTS: The expressions of Stat3 and p-Stat3 in EOC were
      significantly higher than in normal ovarian epithelial tissues or benign ovarian
      tumor tissues (P < 0.0125) and the expression of Stat3 protein was highly
      correlated with the expression of p-Stat3 protein (P < 0.01). The positive rate
      of Stat3 in stages of III and IV (96.9%) was significantly higher than in stages
      of I and II (72.2%) (P < 0.05). Meanwhile, p-Stat3 expression was significantly
      correlated with disease stage, degree of differentiation and lymph node
      metastasis. Along with higher clinical stage (P < 0.05), p-Stat3 expression was
      gradually increased. The p-Stat3 expression was negatively correlated with the
      prognosis of EOC patients (P < 0.01). CONCLUSION: Overexpression and
      overactivation of Stat3 was found in EOC tissues, and the constitutive activation
      of Stat3 signaling pathway may play an important role in the invasion and
      prognosis of EOC.

PMID- 20149043
TI  - Primary chemotherapy patterns for ovarian cancer treatment in Japan.
AB  - AIMS: Evidence-based clinical practices can improve patient outcomes, especially
      in the area of chemotherapy. In Japan, it is not known how well physicians adhere
      to evidence-based chemotherapy guidelines. This study aimed to assess physician
      compliance with national guidelines for ovarian cancer primary chemotherapy in
      Japan. METHODS: Using an administrative database, we analyzed 209 cases of
      surgical laparotomy without neoadjuvant chemotherapy as the primary intervention
      for adnexal cancer. Cases were identified across seven teaching hospitals between
      2003 and 2006. RESULTS: Of the 136 patients receiving inpatient chemotherapy, 101
      cases (74%) were treated with platinum-taxane therapy. In five hospitals,
      platinum-taxane therapy was used in more than 75% of patients, compared to 56%
      and 32% in the other two hospitals, respectively. The proportion of patients
      receiving paclitaxel and carboplatin concomitant therapy (TC therapy) was 67%,
      although significant variation was noted between hospitals (range 32% to 94%, P <
      0.001). Of the 91 patients receiving TC therapy, 59 (65%) were given full-dose
      monthly regimens, while 32 cases (35%) were treated with divided doses weekly.
      Weekly TC therapy was more frequently provided in hospitals with a low volume of
      patients receiving TC therapy. Patients under the age of 65 receiving inpatient
      chemotherapy were more likely to receive full-dose regimens than patients 65 or
      older (68% vs 43%, P = 0.005). Publication of national treatment guidelines did
      not appear to substantially impact chemotherapy practice patterns. CONCLUSIONS:
      Adherence to standardized chemotherapy was comparable to rates in European
      countries, although rates among hospitals differed significantly. Elderly
      patients were more likely to receive divided-dose regimens.

PMID- 20149044
TI  - Massive peritoneal fluid and markedly elevated serum CA125 and CA19-9 levels
      associated with an ovarian endometrioma.
AB  - Endometriosis associated with ascites is an uncommon condition, but nevertheless
      important because it mimics the presentation of ovarian malignancy. We present
      the case of a 34-year-old woman who was admitted with the acute onset of
      abdominal pain and distension. A pelvic sonogram showed a large amount of
      peritoneal fluid with echogenic material and a 10-cm complex cystic structure,
      which appeared to be an enlarged left ovary. The concentrations of CA125 and CA19
      9 were 548.1 and 7604 IU/mL, respectively. On the second day of admission, an
      exploratory laparoscopy was performed, which revealed a ruptured left ovarian
      cyst consistent with an endometrioma. A laparoscopic left adnexectomy was
      therefore performed. The histological examination of the specimen confirmed the
      diagnosis of an endometrioma. After a 12-month follow-up period, the patient
      showed no recurrence of the endometrioma or peritoneal fluid accumulation. In
      most instances, the presence of massive ascites is associated with malignancies,
      tuberculosis, or a perforated viscus. The information provided in the present
      report is important to both gynecologists and oncologists because it shows that
      an ovarian cyst with ascites and highly elevated CA125 and CA19-9 levels might be
      benign.

PMID- 20149045
TI  - Treatment of clomiphene citrate-related ovarian cysts in a prospective randomized
      study. A single center experience.
AB  - AIM: The present study aims to compare the effectiveness of placebo, low dose and
      very low dose oral contraceptives (OC) in the treatment of clomiphene citrate
      (CC)-related ovarian cysts. METHODS: A prospective randomized placebo controlled
      study was undertaken at the Infertility Department of Dr. Zekai Tahir Burak
      Women's Health Education and Research Hospital. A total of 3250 primary infertile
      patients were administered CC for ovulation induction because of ovulatory
      dysfunction and/or unexplained infertility. One hundred and eighty-six women who
      were diagnosed with CC-related ovarian cysts greater than 20 mm on the third day
      of the following menstrual cycle, were eligible for the study. Group 1 (n = 62)
      was treated with very low dose OC (100 microg levonorgestrel + 20 microg ethinyl
      estradiol [EE]), group 2 (n = 62) with low dose OC (150 microg desogestrel + 30
      microg EE) and group 3 (n = 62) with a placebo. The first control was 4 weeks
      later. Women with persistent cysts (n = 57) were called in 4 weeks later to
      continue the same treatment. RESULTS: Demographic data were similar among the
      groups. At the first month, the regression rates of ovarian cysts were 64.5, 61.3
      and 66.1% in groups 1, 2 and 3, respectively (P = 0.849). Among the 57 women (20,
      19 and 18 from groups 1, 2 and 3, respectively) with persistent cysts, the
      regression rates were 65.0, 63.2 and 55.6%, respectively at the second month (P =
      0.821). Persistence of ovarian cysts was significantly higher in women with a
      longer duration of CC treatment than in women with a shorter duration (P <
      0.001). CONCLUSION: Any treatment might be appropriate for patients with a CC
      related ovarian cyst. However, there is no evidence to administer OC for treating
      CC-related ovarian cysts. Expectant management may also achieve similar success
      rates.

PMID- 20149046
TI  - Functional and anatomic assessments for transobturator vaginal tape inside-out
      operation for urodynamic stress incontinence.
AB  - AIM: The aim of the present study was to assess by urodynamic study and chain
      urethrocystography the functional and anatomic changes before and after
      transobturator vaginal tape inside-out (TVT-O) operation. METHODS: From January
      2005 to February 2006, 35 women were enrolled who had urodynamic stress
      incontinence, with or without intrinsic sphincter deficiency, and had undergone
      TVT-O with regular follow-up. Investigations, including pelvic examination, pad
      test, urodynamic study, chain urethrocystography and questionnaire with short
      forms of Urogenital Distress Inventory and Incontinence Impact Questionnaire,
      were performed pre- and postoperatively. RESULTS: The mean follow-up period was
      12.8 months. The subjective and objective cure rates were 80 and 71.4%,
      respectively. The maximal urethral pressure was significantly decreased (from
      67.0 to 58.9 cmH(2)O) after surgery and bladder neck mobility was reduced.
      Quality of life assessment revealed significant improvement after TVT-O.
      CONCLUSION: TVT-O is an effective operation for female urodynamic stress
      incontinence. Improved postoperative bladder neck mobility showed anatomic
      correction, indicating a hammock effect. The decreased maximal urethral pressure
      may reflect neurogenic damage during surgery; thus, minimal dissection and
      avoidance of unnecessary dissection to prevent periurethral damage are advised.

PMID- 20149047
TI  - Transvaginal cystocele correction: Midterm results with a transobturator tension
      free technique using a combined bovine pericardium/polypropylene mesh.
AB  - AIMS: To describe the benefits and complications of a combined bovine/pericardium
      polypropylene mesh for severe vaginal wall prolapse at midterm follow up.
      METHODS: Retrospective analysis of patients with stages 3 and 4 pelvic prolapse
      undergoing cystocele repair using the combined mesh. RESULTS: Between June 2004
      and April 2006 36 patients were treated. The median follow up was 35 months. Two
      patients experienced de novo urgency (5.6%). Resolution of prolapse was achieved
      in 91.7% of patients. Ten percent of those with urinary incontinence continued to
      suffer from incontinence after surgery. There was a significant improvement in
      the quality of life in cases with associated urinary incontinence, and in the
      sexual lives and constipation of all patients. Two cases of vaginal perforation
      (5.6%) and three cases of vaginal erosion (8.3%) were described. CONCLUSIONS: The
      use of a composite bovine pericardium/polypropylene mesh for cystocele correction
      is feasible and safe, yielding good results at midterm follow up.

PMID- 20149048
TI  - Relevance of declines in serum human chorionic gonadotropin levels to the
      management of persistent ectopic pregnancy.
AB  - AIM: To evaluate postoperative declines in serum human chorionic gonadotropin
      (hCG) levels (percentages of preoperative hCG levels) to rule out persistent
      ectopic pregnancy (PEP). METHODS: A retrospective study was conducted on 50
      patients who underwent laparoscopic salpingotomy between April 1995 and March
      2008. The postoperative course was divided into four periods: (period A: days 1
      2; period B: days 3-4; period C: days 5-6; and period D: days 7-8), and the
      postoperative serum hCG declines in the PEP and control groups (successfully
      treated patients) were compared. A cutoff value of serum hCG decline to rule out
      PEP was established by receiver operating characteristic (ROC) analysis. RESULTS:
      Ten of the 50 patients (20%) were diagnosed with PEP. There were no differences
      in clinical findings or preoperative serum hCG levels between the two groups.
      From period C, the serum hCG decline in the control group was significantly
      greater than in the PEP group, and all individual serum hCG declines in the PEP
      group were outside the 95% confidence interval of the control group. Furthermore,
      analysis by ROC using a 14% decline in postoperative serum hCG as a cutoff
      revealed that the specificity and sensitivity of the test were equal to 100% from
      period C. CONCLUSION: Declines in serum hCG during period C (days 5-6) constitute
      an important marker of the presence or absence of PEP. Decisions regarding a
      second intervention for PEP should be made by this time postoperatively.

PMID- 20149049
TI  - Reality of the G-spot and its relation to female circumcision and vaginal
      surgery.
AB  - AIM: To clarify the reality of the G-spot anatomically, functionally and
      histologically, and to determine the possible effect of female circumcision and
      anterior vaginal wall surgery on the integrity and function of the G-spot.
      METHODS: A controlled descriptive and comparative cohort prospective study was
      conducted at Kasr El Aini School of Medicine, Cairo University, Cairo, Egypt, of
      50 uncircumcised and 125 circumcised women with small to moderate anterior
      vaginal wall descent. Preoperative sexual examination was performed to map the
      site of the G-spot and other anatomical landmarks on the anterior vaginal wall
      and to verify the associated circumcision state. Pre- and postoperative sexual
      assessment and histological examination of different mapped sites in the anterior
      vagina were also conducted. RESULTS: Histological findings, results of the
      anatomical and sexual mapping of the anterior vaginal wall and sexual scores were
      recorded. The G-spot was proved functionally in 144 (82.3%) of women and
      anatomically in 95 (65.9%). The latter appeared as two small flaccid balloon-like
      masses on either side of the lower third of the urethra and were named 'the
      sexual bodies of the G-spot'. These bodies were significantly detected in all
      histo-positive cases in the circumcised women and in the uncircumcised women who
      had small or average clitorises. The G-spot was also proved histologically in
      47.4% of all cases and was formed of epithelial, glandular and erectile tissue.
      Sex scores were significantly higher in the histo-positive cases with sexual
      bodies but significantly dropped after anterior vaginal wall surgery. In
      contrast, female circumcision rarely alters the scores. CONCLUSION: The G-spot is
      functional reality in 82.3% of women, an anatomical reality in 54.3% and a
      histological reality in 47.4%. Anterior vaginal wall surgery usually affects the
      G-spot and female sexuality, but female circumcision rarely affects them.

PMID- 20149050
TI  - Moyamoya-disease-related ischemic stroke in the postpartum period.
AB  - Stroke during pregnancy or the puerperium is an extremely rare yet serious cause
      of perinatal morbidity and mortality. Moyamoya disease, a cerebrovascular
      occlusive pathology with a female predominance, may become symptomatic for the
      first time in association with pregnancy. A 36-year-old woman with postpartum pre
      eclampsia suddenly developed hemiparesis in the left arm with dysarthria after
      the initiation of antihypertensive measures. Cranial magnetic resonance imaging
      and angiography revealed acute ischemic lesions in the right hemisphere along
      with the steno-occlusive lesions of bilateral terminal portions of the internal
      carotid artery, indicating Moyamoya disease. With anti-platelet medication, the
      patient recovered gradually and was diagnosed as having Moyamoya disease using
      conventional angiography 3 months postpartum. In this case, the fluctuations in
      blood pressure in association with pre-eclampsia appear to have exacerbated the
      clinical symptoms of Moyamoya disease. As such, Moyamoya disease should be
      considered as an underlying disease of ischemic stroke associated with pregnancy.

PMID- 20149051
TI  - Prenatal diagnosis of mosaic ring 22 duplication/deletion with terminal 22q13
      deletion due to abnormal first trimester screening and choroid plexus cyst
      detected on ultrasound.
AB  - We report a rare case of mosaic ring chromosome 22 duplication/deletion in a
      fetus for whom karyotype analysis was required because of an abnormal finding in
      the maternal serum screening test and a choroid plexus cyst detected on prenatal
      ultrasound. Additional prenatal study of the amniotic fluid by fluorescence in
      situ hybridization was performed and the terminal 22q13.3 deletion was detected
      on ring chromosome. The final karyotype was 45,XX,
      22[3]/46,XX,r(22)(p11q13.2)[63]/46,XX,idicr(22)(p11q13.2;p11q13.2)[2]dn.ishder(22
      (N25+, ARSA-, ter-). The pegnancy was terminated. Cytogenetic analysis of the
      intracardiac blood also revealed ring 22 mosaicism with only one metaphase spread
      with idicr(22) as the unstable isodicentric rings are subsequently lost from most
      cells. We discuss the prenatal diagnosis of this rare condition.

PMID- 20149052
TI  - Two cases of reversal of twin-twin transfusion syndrome diagnosed by measuring
      hourly fetal urine production.
AB  - Reversal of twin-twin transfusion syndrome (TTTS) is a rare complication of
      monochorionic pregnancy. Diagnostic criteria and satisfactory therapeutic options
      have not been reported. We make a suggestion of diagnosis and therapy for
      reversal of TTTS. We report two cases of reversal of TTTS. Measurement of the
      fetal urine production rate was useful for management and better comprehension of
      the cases. In case 1, double intrauterine fetal demise occurred before the
      criteria for TTTS were fulfilled, in which each fetal urine production rate
      reversed prior to the change of amniotic fluid volume. In case 2, elevated urine
      production was noted prior to progressive polyhydroamnios and congestive heart
      failure in the new recipient and the fetoscopic laser photocoagulation of the
      placental communicating vessels was performed successfully before the criteria
      for TTTS were fulfilled. Both infants required intensive care, but developed
      normally and showed no neurologic complications at 2 years after birth. Hourly
      fetal urine production rate was useful for immediate diagnosis of reversal of
      TTTS, and laser photocoagulation of the placental communicating vessels is thus a
      method for the correction of the fetal blood flow imbalance in cases of reversal
      of the donor-recipient phenotype in TTTS.

PMID- 20149053
TI  - Free peritoneal cyst with histologic properties of amniotic epithelium observed
      in a woman pregnant with twins.
AB  - We report an interesting case of a free peritoneal cyst in a woman pregnant with
      twins. As far as we know, a cyst with histologic properties similar to the
      metaplastic stratified squamous epithelium of the amnion has not been reported. A
      20-year-old Japanese woman pregnant with twins underwent cesarean section at 29
      weeks of gestation. A simple serous cyst 5 cm in diameter was found at excavatio
      vesicouterina. The cyst was not attached to the surrounding organs, and was
      located independent of any other tissues in the patient's abdominal cavity.
      Histologic examination revealed that the cyst wall was composed of three major
      layers (epithelium, mesenchyme and mesothelium) with no vessels.
      Immunohistochemical staining with human chorionic gonadotropin (HCG),
      cytokeratins, vimentin, placental alkaline phosphatase (PAP) and cluster of
      differentiation (CD) 31, showed that the cyst wall had characteristic features of
      the amniotic membrane. Alleles of the patient's husband were not identified when
      the cyst was genotyped. Some of the patient's loci were deleted and others showed
      a structurally heterogeneous pattern. These findings suggest that the cyst was
      derived not from the ovum parthenogenesis, but from the patient's somatic cells
      and could have been incubated by ascites.

PMID- 20149054
TI  - Luteoma-induced fetal virilization.
AB  - A pregnancy luteoma represents an unusual response of ovarian stromal cells to
      the altered hormonal levels of pregnancy. It is a distinctive non-neoplastic
      lesion characterized by solid proliferations of luteinized cells resulting in a
      tumor-like ovarian enlargement. Most patients are asymptomatic; the ovarian
      enlargement is usually discovered incidentally at cesarean section or during
      postpartum tubal ligation. We report a typical case that we found at cesarean
      section to be associated with a virilized infant who manifested clitoromegaly and
      labial fusion. We detected an increased level of testosterone in the maternal
      patient. We concluded that the ovarian luteoma induced the fetal virilization.

PMID- 20149055
TI  - Endometriosis in a patient with Rokitansky-Kuster-Hauser syndrome.
AB  - Endometriosis in Rokitansky-Kuster-Hauser syndrome has been reported only once
      previously. We present here a case of endometrioma in a patient with Rokitansky
      Kuster-Hauser syndrome. A 26-year-old patient with Rokitansky-Kuster-Hauser
      syndrome presented with abrupt pain in the left iliac quadrant. A mass was
      confirmed by sonography. Laparoscopic inspection revealed no uterus. The mass was
      removed laparoscopically. Endometriosis was confirmed histologically. If
      endometrioma in a patient with Rokitansky-Kuster-Hauser syndrome is associated
      with a small rudimentary unicornis uterus with a small endometrial cavity,
      endometriosis can be assumed to have developed by retrograde menstruation theory.
      Because the patient did not have a functioning endometrium, her endometrioma is
      assumed to have arisen from coelomic metaplasia.

PMID- 20149056
TI  - Herniation of fallopian tube through perforated uterine wall during previous
      first trimester surgical abortion in an infertile patient.
AB  - A unique case of fallopian tube herniation into the endometrial cavity after
      dilatation and curettage is presented. A 28-year-old patient who had secondary
      infertility for 2 years following dilatation and curettage without any other
      specific complaint was evaluated by laparoscopy and hysteroscopy. During these
      procedures, herniation of the right tube and infundibulopelvic ligament into the
      uterine cavity were observed. The herniation was repaired through a
      minilaparotomy incision.

PMID- 20149057
TI  - Extranodal Rosai-Dorfman disease involving bilateral ovaries in a patient with a
      ventriculoperitoneal shunt.
AB  - Rosai-Dorfman disease (RDD) is a rare condition of unknown etiology, and female
      genital tract involvement in RDD is uncommon. We describe the first case of RDD
      with bilateral ovarian involvement in a patient implanted with a
      ventriculoperitoneal (VP) shunt. The patient was a 17-year-old Japanese woman who
      had undergone radiotherapy, surgery for extranodal RDD involving the brain, and
      VP shunt insertion at age 12. Bilateral pelvic masses were incidentally detected
      on a computed tomography scan. She underwent laparotomy for lesion extirpation.
      On abdominal washing cytology, histiocytes showing emperipolesis were identified.
      Bilateral salpingo-oophorectomy was performed instead of extirpation, as it was
      difficult to identify the lesion margins. At 24 months after surgery, the patient
      is well and has not developed local recurrence. Thus, RDD can recur because of
      implantation of lesion cells into the abdominal cavity through a VP shunt, as is
      observed in the case of cerebral neoplasms.

PMID- 20149058
TI  - Fos-related activator-1 is overexpressed in oral squamous cell carcinoma and
      associated with tumor lymph node metastasis.
AB  - BACKGROUND: Previously, we established an in vitro cellular carcinogenesis model
      of oral squamous cell carcinoma (OSCC), including the human immortalized oral
      epithelia cells (HIOECs) and its derived cancerous HB cells. Then, expression
      microarray analysis showed that the gene encoding fos-related activator-1 (Fra-1)
      was significantly upregulated in the cancerous HB cells compared with HIOECs.
      METHODS: To confirm the expression of Fra-1 at mRNA and protein levels by real
      time PCR and western blotting analysis in the carcinogenesis model of OSCC and
      CAL27 cells. To investigate Fra-1 expression in clinical samples from 30 primary
      OSCC patients by immunohistochemistry. RESULTS: Fra-1 expression was increased
      both at mRNA and protein levels in this carcinogenesis model of OSCC and CAL27
      cells. Nuclear and cytoplasmic Fra-1 protein expressions both increased in the
      cancerous tissues compared with those in the paired adjacent non-malignant
      epithelia (nuclear: P < 0.001, cytoplasmic: P = 0.003). A higher level of nuclear
      Fra-1 expression was seen in the tumor samples of patients with lymph node
      metastasis than those without lymph node metastasis (5.07 +/- 1.33 vs 3.81 +/-
      1.33, P = 0.023). Higher level of Fra-1 expression was also found in the tumor
      invasive margin than tumor center. CONCLUSIONS: Fra-1 is a positive gene of OSCC
      development and progression, Fra-1 can be used as a potential therapeutic target
      gene and an additional marker for evaluation of lymph node metastasis.

PMID- 20149059
TI  - Cytogenetic characterization of head and neck squamous cell carcinoma cell lines
      as model systems for the functional analyses of tumor-associated genes.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a solid malignant neoplasm
      exhibiting aggressive phenotypes and high recurrence rates. To improve its
      clinical management, understanding the molecular basis of HNSCC development is of
      critical importance. For the investigation of tumor-associated genes, functional
      analyses in well-characterized tumor cell systems are required. To establish an
      experimental platform, a set of 20 HNSCC cell lines was screened for genetic
      imbalances by chromosomal comparative genomic hybridization (cCGH). Frequent DNA
      copy number gains were detected on 3q26.3-qter, 5p, 7p11-p13, 8q23-qter, 9p11
      p13, 9q31-qter, 11q13 and 20q13.1, whereas copy number losses were found on 3p,
      4p, 4q32.1-qter, 8p11-p12 and 18q22 in agreement with previous observations on
      genetic aberrations detected in primary HNSCC specimens. Subsequent mRNA
      expression analysis of 11q13 candidate genes CCND1 and CTTN revealed that HNSCC
      cell lines exhibiting a DNA copy number gain on 11q13 had a higher transcript
      level of CCND1 and CTTN compared with HNSCC cell lines without 11q13 copy number
      gain (P = 0.014 and P = 0.009, respectively). Furthermore, CCND1 and CTTN
      amplification as detected by fluorescence in situ hybridization correlated with
      protein expression as assessed by immunocytochemistry. In summary, the
      cytogenetic characterization illustrates that this set of HNSCC cell lines is
      representative for the HNSCC genome and provides tumor model systems for detailed
      analysis of genes with a possible role in the pathomechanism of head and neck
      tumors.

PMID- 20149060
TI  - Study of growth factors and receptors in carcinoma ex pleomorphic adenoma.
AB  - Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor
      derived from a pre-existing pleomorphic adenoma. It is a good model to study the
      evolution of carcinogenesis, starting with in situ areas to frankly invasive
      carcinoma. Growth factors are associated with several biological and neoplastic
      processes by transmembrane receptors. In order to investigate, by
      immunohistochemistry, the expression of some growth factors and its receptors
      [EGF receptor, fibroblast growth factor, fibroblast growth factor receptor 1,
      fibroblast growth factor receptor 2, hepatocyte growth factor, c-Met,
      transforming growth factor (TGF) beta1, TGFbetaR-II and insulin-like growth
      factor receptor 1] in the progression of CXPA, we have used ten cases of CXPA in
      several degrees of invasion- intracapsular, minimally and frankly invasive
      carcinoma- with only epithelial component. Slides were qualitatively and semi
      quantitatively evaluated according to the percentage of stained tumor cells from
      0 to 3 (0 = less than 10%; 1 = 10-25%; 2 = 25-50%; 3 = more than 50% of cells).
      Malignant epithelial cells starting with in situ areas showed stronger expression
      than luminal cells of pleomorphic adenoma for all antibodies. Most of the
      intracapsular, minimally and frankly invasive CXPA presented score 3. However,
      score 2 was more evident in the frankly invasive one. In small nests of invasive
      carcinoma, negative cells were observed probably indicating that the
      proliferative process is replaced by the invasive mechanism. Altogether this data
      infers that these factors may contribute to cell proliferation during initial
      phases of the tumor.

PMID- 20149061
TI  - Comparing dose-response measurements of oral habits on oral leukoplakia and oral
      submucous fibrosis from a community screening program.
AB  - BACKGROUND: Many studies have reported that the interaction and dose-response
      effects of betel quid chewing, tobacco smoking and alcohol drinking habits are
      important risk factors for oral cancer and precancerous lesions or conditions.
      These results are useful for comparing statistics, but may not be informative for
      personal disease-related information. METHODS: This study used data from a
      community screening program to evaluate the dose-response effects of daily
      frequency and duration from oral habits in Taiwan. The receiver operating
      characteristic (ROC) curves were further used to compare exposure measurements on
      indicating the occurrence of lesions/conditions. RESULTS: Our results showed that
      the highest prevalence was found in leukoplakia (11.1%) and followed by oral
      submucous fibrosis (OSF, 4.4%). Betel quid chewing habit was found to have dose
      response effects on leukoplakia and OSF, cigarette smoking habit only has the
      dose-response effect on leukoplakia, and alcohol drinking was not associated with
      both oral precancers. The daily frequency of chewing habit is a better indicator
      than other dose-response measurements for the occurrence of precancers. In
      addition, the cut-off points of two to five counts per day have about 60-82% of
      sensitivities and 79-88% of specificities. CONCLUSIONS: The cut-off points from
      ROC curves can provide an informative message to people with oral habits and
      their chances of developing diseases. High daily frequency of chewing can lead to
      excessive irritation to oral mucosa. Although the tobacco is never added to
      chewing quid in Taiwan, intensive irritation may play an important role in
      developing oral precancers in Taiwan.

PMID- 20149062
TI  - Modified section method for laser-welding of ill-fitting cp Ti and Ni-Cr alloy
      one-piece cast implant-supported frameworks.
AB  - This study aimed to verify the effect of modified section method and laser
      welding on the accuracy of fit of ill-fitting commercially pure titanium (cp Ti)
      and Ni-Cr alloy one-piece cast frameworks. Two sets of similar implant-supported
      frameworks were constructed. Both groups of six 3-unit implant-supported fixed
      partial dentures were cast as one-piece [I: Ni-Cr (control) and II: cp Ti] and
      evaluated for passive fitting in an optical microscope with both screws tightened
      and with only one screw tightened. All frameworks were then sectioned in the
      diagonal axis at the pontic region (III: Ni-Cr and IV: cp Ti). Sectioned
      frameworks were positioned in the matrix (10-Ncm torque) and laser-welded.
      Passive fitting was evaluated for the second time. Data were submitted to anova
      and Tukey-Kramer honestly significant difference tests (P < 0.05). With both
      screws tightened, one-piece cp Ti group II showed significantly higher misfit
      values (27.57 +/- 5.06 microm) than other groups (I: 11.19 +/- 2.54 microm, III:
      12.88 +/- 2.93 microm, IV: 13.77 +/- 1.51 microm) (P < 0.05). In the single-screw
      tightened test, with readings on the opposite side to the tightened side, Ni-Cr
      cast as one-piece (I: 58.66 +/- 14.30 microm) was significantly different from cp
      Ti group after diagonal section (IV: 27.51 +/- 8.28 microm) (P < 0.05). On the
      tightened side, no significant differences were found between groups (P > 0.05).
      Results showed that diagonally sectioning ill-fitting cp Ti frameworks lowers
      misfit levels of prosthetic implant-supported frameworks and also improves
      passivity levels of the same frameworks when compared to one-piece cast
      structures.

PMID- 20149063
TI  - Do school-based dental sealant programs reach higher risk children?
AB  - OBJECTIVES: This report compares sealant prevalence by caries risk status among
      third graders at Ohio schools with and without school-based dental sealant
      programs (S-BSPs), and estimates the percent of children receiving sealants in S
      BSPs who are higher risk for dental caries. METHODS: We analyzed data from a
      statewide open-mouth oral health survey of Ohio third grade schoolchildren for
      sealant prevalence by S-BSP availability and caries risk classification. Children
      were classified as higher or lower risk for dental caries based on school lunch
      program enrollment and other non-clinical access-related indicators. Differences
      between groups were evaluated by the chi-square test (P < 0.05). RESULTS: At
      schools with no S-BSPs, higher risk children were less likely to have dental
      sealants than lower risk children (28.7 percent versus 42.7 percent, P < 0.001).
      At schools with S-BSPs, sealant prevalence for both risk categories was
      equivalent for higher and lower risk children (59.4 percent, 63.4 percent, P =
      0.428). Higher risk children at schools with S-BSPs were more than twice as
      likely to have a sealant as higher risk children at non-S-BSP schools (59.4
      percent versus 28.7 percent, P < 0.001). Of higher risk children with at least
      one sealant, 61 percent attended a school with an S-BSP compared with 12.3
      percent of lower risk children with at least one sealant. Higher risk children
      accounted for at least 75 percent of children receiving sealants through S-BSPs.
      CONCLUSIONS: In Ohio, targeting S-BSPs by family income-based school-level
      criteria was effective in reaching higher risk children.

PMID- 20149064
TI  - Oral health status of New Hampshire Head Start children, 2007-2008.
AB  - OBJECTIVES: We report on the baseline prevalence and severity of dental caries of
      children enrolled in the New Hampshire Head Start program during the 2007-2008
      school year. METHODS: We selected a random cluster sample of 607 children aged 3
      5 years attending 27 Head Start centers across the state. Four volunteer dentists
      provided oral examinations and determined the presence of untreated dental
      caries, caries experience, and treatment urgency. RESULTS: Overall, 40 percent of
      the participating children had experienced dental caries, and 31 percent had at
      least one untreated decayed tooth. Approximately 22 percent of the children had
      evidence of maxillary anterior caries, 23 percent were in need of dental care,
      and < 1 percent needed urgent care. CONCLUSIONS: The prevalence of dental caries
      is comparable with that reported by Head Start programs elsewhere. The prevalence
      of caries affecting maxillary anterior teeth is higher. Further studies should
      examine state-specific barriers to dental care among this population.

PMID- 20149065
TI  - Assessment of predictors of global self-ratings of oral health among Korean
      adults aged 18-95 years.
AB  - OBJECTIVES: The aims of this study were to assess predictors of global self
      ratings of oral health (GSROH) and to examine whether they varied by age among
      Korean adults aged 18-95 years. METHODS: Data from 4,546 adults aged 18-95 years
      completing the Korean National Oral Health Survey 2006 were included in the
      analysis. RESULTS: Subjects' mean age was 43.5 years, with 12.1 percent aged > or
      = 65 years; 47.8 percent were men; and 2.5 percent were edentulous. The
      predictors of GSROH in adults were number of missing teeth, concern about oral
      health, and difficulty in chewing. While wearing removable dentures was
      associated only in elders, perceived treatment need was associated in younger age
      groups. The number of decayed and filled teeth was significant only in the 18-44
      age group. CONCLUSIONS: GSROH status was associated with measures of oral
      disease, oral functional problems, oral health behaviors, concerns, and perceived
      treatment needs, and it varied by age.

PMID- 20149066
TI  - Performance of atraumatic restorative treatment (ART) depending on operator
      experience.
AB  - OBJECTIVES: Oral health care is not of major interest in developing countries
      because of lack of infrastructure and professional manpower. Therefore,
      atraumatic restorative treatment (ART) was introduced by the World Health
      Organization to be performed by dental auxiliary personnel. The aim of this study
      was to evaluate the performance of ART depending on operator-experience in The
      Republic of The Gambia. METHODS: One hundred twenty-eight newly inserted
      restorations were followed up for 12 months using the clinical ART index in a
      prospective and blinded study design. The patients were randomly assigned to
      operators. The clinical performance was compared among three groups: trainees,
      experienced Community Oral Health Workers (COHW), and professional dentists. The
      difference in success rates was calculated at a 95 percent confidence interval.
      RESULTS: There was a statistically significant difference between trainees and
      dentists in performing leakage/gap-free one-surface restorations (P < 0.05). No
      significant differences were found between the two groups of auxiliaries
      (trainees versus experienced COHWs, P > 0.05). Finally, both groups--experienced
      COHWs and dentists--performed restorations not showing statistically significant
      differences (P > 0.05). CONCLUSIONS: For The Republic of The Gambia--especially
      for areas with underdeveloped medical infrastructure--training and assignment to
      perform ART can be recommended for auxiliary dental staff of Community Oral
      Health Workers.

PMID- 20149067
TI  - Validating an automated sleep spindle detection algorithm using an individualized
      approach.
AB  - The goal of the current investigation was to develop a systematic method to
      validate the accuracy of an automated method of sleep spindle detection that
      takes into consideration individual differences in spindle amplitude. The
      benchmarking approach used here could be employed more generally to validate
      automated spindle scoring from other detection algorithms. In a sample of Stage 2
      sleep from 10 healthy young subjects, spindles were identified both manually and
      automatically. The minimum amplitude threshold used by the Prana (PhiTools,
      Strasbourg, France) software spindle detection algorithm to identify a spindle
      was subject-specific and determined based upon each subject's mean peak spindle
      amplitude. Overall sensitivity and specificity values were 98.96 and 88.49%,
      respectively, when compared to manual scoring. Selecting individual amplitude
      thresholds for spindle detection based on systematic benchmarking data may
      validate automated spindle detection methods and improve reproducibility of
      experimental results. Given that interindividual differences are accounted for,
      we feel that automatic spindle detection provides an accurate and efficient
      alternative approach for detecting sleep spindles.

PMID- 20149068
TI  - Measuring the error in sleep estimation in normal subjects and in patients with
      insomnia.
AB  - The aims of this study were to measure the error in sleep estimation in normal
      controls and subjects with primary insomnia to establish the minimum amount of
      sleep needed for reliable subjective estimation and to depict the distribution of
      the error in sleep estimation in both groups. A two-step retrospective (study 1)
      and prospective (study 2) validation study was carried out. Study 1 included 288
      normal subjects [176 females and 112 males, mean age 58.5 years, standard
      deviation (SD) 7.23]. Study 2 included 159 patients (98 females and 61 males;
      mean age 49.1 years, SD 12.71) with primary insomnia. Participants underwent a
      full-night polysomnographic study, followed by a morning assessment of subjective
      sleep parameters. A misperception index (MI) was computed using the following
      formula: MI = [objective total sleep time (oTST)-subjective total sleep time
      (sTST)]/oTST. The statistical properties of this index were analysed in detail in
      both groups. In controls, the Bland-Altman test demonstrated the reliability of
      this index for values of oTST >120 min. Healthy subjects estimated their sleep
      time correctly, while insomniacs largely underestimated their sleep time.
      Statistical analysis of the distribution of MI in insomnia patients disclosed the
      presence of two subgroups, one with moderate sleep misperception (132 patients)
      and the other with high sleep misperception (27 patients). The latter presented
      MI values >or=0.9, exhibiting statistical properties different from those with MI
      <0.9 and from normal subjects. The MI gives a reliable and immediate description
      of sleep misperception in healthy and insomnia subjects. Its application supports
      the existence of the high misperception of insomnia as a separate pathological
      entity.

PMID- 20149069
TI  - Genome-wide linkage of obstructive sleep apnoea and high-density lipoprotein
      cholesterol in a Filipino family: bivariate linkage analysis of obstructive sleep
      apnoea.
AB  - Increasing evidence supports an association between obstructive sleep apnoea
      (OSA) and metabolic syndrome (MeS) in both children and adults, suggesting a
      genetic component. However, the genetic relationship between the diseases remains
      unclear. We performed a bivariate linkage scan on a single Filipino family with a
      high prevalence of OSA and MeS to explore the genetic pathways underlying these
      diseases. A large rural family (n = 50, 50% adults) underwent a 10-cM genome-wide
      scan. Fasting blood was used to measure insulin, triglycerides, total cholesterol
      and high density lipoprotein (HDL) cholesterol. Attended overnight
      polysomnography was used to quantify the respiratory disturbance index (RDI), a
      measure of sleep apnoea. Body mass index z-scores and insulin resistance scores
      were calculated. Bivariate multipoint linkage analyses were performed on RDI and
      MeS components. OSA prevalence was 46% (n = 23; nine adults, 14 children) in our
      participants. MeS phenotype was present in 40% of adults (n = 10) and 48% of
      children (n = 12). Linkage peaks with a logarithm of odds (LOD) score >3 were
      demonstrated on chromosome 19q13.4 (LOD = 3.04) for the trait pair RDI and HDL
      cholesterol. Candidate genes identified in this region include the killer cell
      immunoglobulin-like receptor genes. These genes are associated with modulating
      inflammatory responses in reaction to cellular stress and initiation of
      atherosclerotic plaque formation. We have identified a novel locus for genetic
      links between RDI and lipid factors associated with MeS in a chromosomal region
      containing genes associated with inflammatory responses.

PMID- 20149072
TI  - Clinical prediction rules for pulmonary embolism: a systematic review and meta
      analysis.
AB  - SUMMARY BACKGROUND: Pretest probability assessment is necessary to identify
      patients in whom pulmonary embolism (PE) can be safely ruled out by a negative D
      dimer without further investigations. OBJECTIVE: Review and compare the
      performance of available clinical prediction rules (CPRs) for PE probability
      assessment. PATIENTS/METHODS: We identified studies that evaluated a CPR in
      patients with suspected PE from Embase, Medline and the Cochrane database. We
      determined the 95% confidence intervals (CIs) of prevalence of PE in the various
      clinical probability categories of each CPR. Statistical heterogeneity was
      tested. RESULTS: We identified 9 CPR and included 29 studies representing 31215
      patients. Pooled prevalence of PE for three-level scores (low, intermediate or
      high clinical probability) was: low, 6% (95% CI, 4-8), intermediate, 23% (95% CI,
      18-28) and high, 49% (95% CI, 43-56) for the Wells score; low, 13% (95% CI, 8
      19), intermediate, 35% (95% CI, 31-38) and high, 71% (95% CI, 50-89) for the
      Geneva score; low, 9% (95% CI, 8-11), intermediate, 26% (95% CI, 24-28) and high,
      76% (95% CI, 69-82) for the revised Geneva score. Pooled prevalence for two-level
      scores (PE likely or PE unlikely) was 8% (95% CI,6-11) and 34% (95% CI,29-40) for
      the Wells score, and 6% (95% CI, 3-9) and 23% (95% CI, 11-36) for the Charlotte
      rule. CONCLUSION: Available CPR for assessing clinical probability of PE show
      similar accuracy. Existing scores are, however, not equivalent and the choice
      among various prediction rules and classification schemes (three- versus two
      level) must be guided by local prevalence of PE, type of patients considered
      (outpatients or inpatients) and type of D-dimer assay applied.

PMID- 20149071
TI  - The spatial dynamics of fibrin clot dissolution catalyzed by erythrocyte-bound
      vs. free fibrinolytics.
AB  - SUMMARY BACKGROUND: Coupling fibrinolytic plasminogen activators to red blood
      cells (RBCs) has been proposed as an effective, yet safe method of
      thromboprophylaxis, because of increased circulation lifetime and reduced
      propensity to induce hemorrhage by selectivity for nascent thrombi rather than
      pre-formed hemostatic clots. OBJECTIVES AND METHODS: We used confocal microscopy
      of fluorescently labeled fibrin and erythrocytes in plasma-derived clots to study
      the spatial dynamics of lysis catalyzed by RBC-coupled vs. free plasminogen
      activators (RBC-PA vs. PA). RESULTS: Clot lysis catalyzed by free PA progressed
      gradually and uniformly. In contrast, distinct holes formed surrounding RBC-PA
      while the rest of the clot remained intact until these holes enlarged
      sufficiently to merge, causing sudden clot dissolution. Compared with naive RBCs
      within clots lysed by free PA, RBC-PA moved faster inside the fibrin network
      prior to clot dissolution, providing a potential mechanism for spatial
      propagation of RBC-PA induced lysis. We also showed the focal nature of
      fibrinolysis by RBC-PA as dense loading of PA onto RBCs initiates more efficient
      lysis than equal amounts of PA spread sparsely over more RBCs. In an in vitro
      model of clots exposed to buffer flow, incorporated RBC-PA increased permeability
      and formed channels eventually triggering clot dissolution, whereas clots
      containing free PA remained intact. CONCLUSIONS: Clot lysis by RBC-PA begins
      focally, has a longer lag phase when measured by residual mass than homogeneous
      lysis by PA, is propagated by RBC-PA motility and provides more effective clot
      reperfusion than free PA, making RBC-PA attractive for short-term
      thromboprophylaxis.

PMID- 20149073
TI  - Pharmacogenetics of acenocoumarol in patients with extreme dose requirements.
AB  - SUMMARY BACKGROUND: There is currently intense debate as to whether
      pharmacogenetic algorithms for estimating the initial dose of coumarins provide a
      more accurate dose than the fixed-dose approach. Recently, it has been suggested
      that the greatest benefit of pharmacogenetic algorithms is observed in patients
      with extreme dose requirements. OBJECTIVES: To identify clinical and genetic
      factors that better characterize patients who need extreme acenocoumarol doses
      for steady anticoagulation state. PATIENTS/METHODS: We reviewed 9538 patients
      with a steady acenocoumarol dose from three Spanish hospitals, selecting 83 who
      took <or= 5.00 mg week(-1) (percentile 5, p5) and 203 taking >or= 30.00 mg week(
      1) (p95). We also selected patients matched by gender and age taking 13.50-14.00
      mg week(-1) (p50). We genotyped VKORC1 (rs9923231), CALU (rs1043550), GGCX
      (rs699664), CYP2C9 (rs1799853; rs1057910), CYP4F2 (rs2108622) and F7 (rs5742910)
      single-nucleotide polymorphisms (SNPs). RESULTS: Comparison between p5 and p95
      revealed five parameters with significant differences: body surface area (BSA) (P
      = 0.006), age, VKORC1, CYP2C9 and CYP4F2 genotypes (all P < 0.001). First VKORC1,
      and second, CYP2C9 SNPs played a strong effect by determining extreme doses,
      particularly in p95. Only one out of 203 p95 had the VKORC1 A-1639A genotype, but
      this subject was CYP2C9*1/*1. In contrast, nine out of 83 p5 carried the VKORC1 G
      1639G genotype, although six of them were CYP2C9*3 homozygotes and another two
      were heterozygotes. Surprisingly, CYP4F2 V433M SNP displayed prevalences that
      suggest that its influence might only be evident when patients are treated with
      high doses. CONCLUSION: Two clinical data, age and BSA, and three SNPs in the
      VKORC1, CYP2C9 and CYP4F2 genes strongly predict outlier patients treated with
      acenocoumarol.

PMID- 20149074
TI  - How to treat cerebral venous and sinus thrombosis.
AB  - SUMMARY: Cerebral venous and sinus thrombosis (CVT) is a rare form of thrombosis,
      with many different clinical manifestations. Better imaging techniques have
      greatly improved the diagnosis, but as a result of the paucity of controlled
      trials, choosing the optimal treatment for each patient often remains a
      challenge. Heparin is generally considered the mainstay of treatment, supported
      by data from a few small trials. More invasive treatment options are available,
      such as endovascular thrombolysis and--in more severe cases--decompressive
      hemicraniectomy. Furthermore, CVT is often accompanied by various neurological
      complications, such as seizures and intracranial hypertension, which require
      specific treatment. In this review we summarize the available treatment options
      for CVT and suggest which therapy should be reserved for which patients.

PMID- 20149075
TI  - Recurrent venous thromboembolism after surgery-provoked versus unprovoked
      thromboembolism.
AB  - SUMMARY BACKGROUND: The incidence of recurrent venous thromboembolism (VTE)
      varies depending on the nature of the initial provoking risk factor(s).
      OBJECTIVES: To compare the incidence and time course of recurrent VTE after
      unprovoked VTE vs. VTE provoked by nine different types of surgery. METHODS:
      Retrospective analysis of linked California hospital and emergency department
      discharge records. Between 1997 and 2007, all surgery-provoked VTE cases had a
      first-time VTE event diagnosed within 60 days after undergoing a major operation.
      The incidence of recurrent VTE was compared during specified follow-up periods by
      matching each surgery-provoked case with three unprovoked cases based on age,
      race, gender, VTE event, calendar year and co-morbidity. RESULTS: The 4-year
      Kaplan-Meier cumulative incidence of recurrent VTE was 14.7% (95%CI: 14.2-15.1)
      in the matched unprovoked VTE group vs. 7.6% (CI: 7.0-8.2) in 11 797 patients
      with surgery-provoked VTE (P < 0.001). The overall risk reduction was 48%, which
      ranged from 64% lower risk (P < 0.001) after coronary bypass surgery to 25% lower
      risk (P = 0.06) after disc surgery. The risk of recurrent VTE 1-5 years after the
      index event was significantly lower in the surgery group (HR = 0.47, CI: 0.41
      0.53). Within the surgery-provoked group, the risk of recurrent VTE was similar
      in men and women (HR = 1.0, CI: 0.8-1.3). CONCLUSIONS: The risk of recurrent VTE
      after surgery-provoked VTE was approximately 50% lower than after unprovoked VTE,
      confirming the view that provoked VTE is associated with a lower risk of
      recurrent VTE. However, there was appreciable heterogeneity in the relative risk
      of recurrent VTE associated with different operations.

PMID- 20149076
TI  - The risk of cancer in patients with venous thromboembolism does not exceed that
      expected in the general population after the first 6 months.

PMID- 20149077
TI  - Interaction between tissue factor pathway inhibitor and factor V levels on the
      risk of venous thrombosis.

PMID- 20149078
TI  - Fine particulate: it matters.

PMID- 20149079
TI  - Biomechanics in hemostasis and thrombosis.
AB  - See also Liu W, Carlisle CR, Sparks EA, Guthold M. The mechanical properties of
      single fibrin fibers. This issue, pp 1030-6; Carlisle CR, Sparks EA, Der Loughian
      C, Guthold M. Strength and failure of fibrin fiber branchpoints. This issue, pp
      1135-8.

PMID- 20149080
TI  - No more mixing tests required for integrated assay systems in the laboratory
      diagnosis of lupus anticoagulants?

PMID- 20149081
TI  - Nitric oxide-sensitive guanylyl cyclase is the only nitric oxide receptor
      mediating platelet inhibition.
AB  - BACKGROUND: The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling
      cascade is involved in the precise regulation of platelet responses. NO released
      from the endothelium is known to activate NO-sensitive guanylyl cyclase (NO-GC)
      in platelets. By the generation of cGMP and subsequent activation of cGMP
      dependent protein kinase (PKG), NO-GC mediates the reduction of the intracellular
      calcium and inhibits platelet adhesion and aggregation. However, NO has been
      postulated to influence these platelet functions also via cGMP-independent
      mechanisms. OBJECTIVE: We studied the effect of NO on platelets lacking NO
      sensitive guanylyl cyclase with regards to aggregation, adhesion, calcium
      mobilization and bleeding time. METHODS AND RESULTS: Here, we show that NO
      signaling leading to inhibition of agonist-induced platelet aggregation is
      totally abrogated in platelets from mice deficient in NO-GC (GCKO). Even at
      millimolar concentrations none of the several different NO donors inhibited
      collagen-induced aggregation of GCKO platelets. In addition, NO neither affected
      adenosine 5'-diphosphate (ADP)-induced adhesion nor thrombin-induced calcium
      release in GCKO platelets. Although the NO-induced cGMP signal transduction was
      totally abrogated cyclic adenosine monophosphate (cAMP) signaling was still
      functional; however, cGMP/cAMP crosstalk was disturbed on the level of
      phosphodiesterase type 3 (PDE3). These in vitro data are completed by a reduced
      bleeding time indicating the lack of NO effect in vivo. CONCLUSIONS: We conclude
      that NO-GC is the only NO receptor in murine platelets mediating the inhibition
      of calcium release, adhesion and aggregation: lack of the enzyme leads to
      disturbance of primary hemostasis.

PMID- 20149082
TI  - Rapid detection of mecA and spa by the loop-mediated isothermal amplification
      (LAMP) method.
AB  - AIM: To develop a detection assay for staphylococcal mecA and spa by using loop
      mediated isothermal amplification (LAMP) method. METHODS AND RESULTS:
      Staphylococcus aureus and other related species were subjected to the detection
      of mecA and spa by both PCR and LAMP methods. The LAMP successfully amplified the
      genes under isothermal conditions at 64 degrees C within 60 min, and demonstrated
      identical results with the conventional PCR methods. The detection limits of the
      LAMP for mecA and spa, by gel electrophoresis, were 10(2) and 10 cells per tube,
      respectively. The naked-eye inspections were possible with 10(3) and 10 cells for
      detection of mecA and spa, respectively. The LAMP method was then applied to
      sputum and dental plaque samples. The LAMP and PCR demonstrated identical results
      for the plaque samples, although frequency in detection of mecA and spa by the
      LAMP was relatively lower for the sputum samples when compared to the PCR
      methods. CONCLUSION: Application of the LAMP enabled a rapid detection assay for
      mecA and spa. The assay may be applicable to clinical plaque samples.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The LAMP offers an alternative detection
      assay for mecA and spa with a great advantage of the rapidity.

PMID- 20149083
TI  - In vitro anti-enterovirus 71 activity of gallic acid from Woodfordia fruticosa
      flowers.
AB  - AIMS: The anti-enterovirus 71 (EV71) activity of six Nepalese plants' extracts
      and gallic acid (GA) isolated from Woodfordia fruticosa Kurz (family; Lythaceae)
      flowers were evaluated in Vero cells. METHODS AND RESULTS: The anti-EV71 activity
      of tested compounds was evaluated by a cytopathic effect reduction method. Our
      results demonstrated that flowers' extracts of W. fruticosa exerted strong anti
      EV71 activity, with a 50% inhibitory concentration (IC(50)) of 1.2 microg ml(-1)
      and no cytotoxicity at a concentration of 100 microg ml(-1), and the derived
      therapeutic index (TI) was more than 83.33. Rivabirin showed no antiviral
      activity against EV71. Furthermore, GA isolated from W. fruticosa flowers
      exhibited a higher anti-EV71 activity than the extract of W. fruticosa flowers,
      with an IC(50) of 0.76 microg ml(-1) and no cytotoxicity at a concentration of
      100 microg ml(-1), and the derived TI was 99.57. CONCLUSIONS: This study
      demonstrated that flower extracts of W. fruticosa possessed anti-EV71 activity
      and GA isolated from these flowers showed stronger anti-EV71 activity than that
      the extracts. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest that the
      GA from W. fruticosa flowers may be used as a potential antiviral agent.

PMID- 20149084
TI  - A versatile internal control for use as DNA in real-time PCR and as RNA in real
      time reverse transcription PCR assays.
AB  - AIMS: To develop and evaluate a TaqMan-based internal amplification control (IAC)
      that can be used as DNA in real-time PCR (qPCR) or as RNA in reverse
      transcription real-time PCR (qRT-PCR) to identify the presence of assay
      inhibition and to evaluate its incorporation into existing qPCR and qRT-PCR
      methods for bacterial detection. METHODS AND RESULTS: A DNA IAC was constructed
      by generating a 198-bp random sequence that was synthesized and inserted into a
      pZErO-2 vector and transformed into Escherichia coli. The RNA IAC was generated
      through in vitro transcription of the DNA IAC. Both IAC formats were tested
      individually in singleplex TaqMan reactions and also included in existing
      multiplex assays. The DNA IAC was incorporated in a Shigella spp. detection qPCR
      assay (targeting ipaH). The RNA IAC was successfully evaluated in a Salmonella
      spp. detection qRT-PCR (using invA mRNA as target). CONCLUSIONS: A highly
      versatile IAC that can be supplemented to qPCR and qRT-PCR pathogen detection
      methods was developed, greatly reducing the confounding effects of false
      negatives because of PCR inhibitors without affecting pathogen detection.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The frequency of false negatives associated
      with qPCR analyses is prevalent in certain matrices, particularly those involving
      complex foods. Hence, the IAC presented here provides a solution to unforeseen
      false-negative reactions in PCR.

PMID- 20149085
TI  - Scale-dependent genetic structure of the Idaho giant salamander (Dicamptodon
      aterrimus) in stream networks.
AB  - The network architecture of streams and rivers constrains evolutionary,
      demographic and ecological processes of freshwater organisms. This consistent
      architecture also makes stream networks useful for testing general models of
      population genetic structure and the scaling of gene flow. We examined genetic
      structure and gene flow in the facultatively paedomorphic Idaho giant salamander,
      Dicamptodon aterrimus, in stream networks of Idaho and Montana, USA. We used
      microsatellite data to test population structure models by (i) examining
      hierarchical partitioning of genetic variation in stream networks; and (ii)
      testing for genetic isolation by distance along stream corridors vs. overland
      pathways. Replicated sampling of streams within catchments within three river
      basins revealed that hierarchical scale had strong effects on genetic structure
      and gene flow. amova identified significant structure at all hierarchical scales
      (among streams, among catchments, among basins), but divergence among catchments
      had the greatest structural influence. Isolation by distance was detected within
      catchments, and in-stream distance was a strong predictor of genetic divergence.
      Patterns of genetic divergence suggest that differentiation among streams within
      catchments was driven by limited migration, consistent with a stream hierarchy
      model of population structure. However, there was no evidence of migration among
      catchments within basins, or among basins, indicating that gene flow only
      counters the effects of genetic drift at smaller scales (within rather than among
      catchments). These results show the strong influence of stream networks on
      population structure and genetic divergence of a salamander, with contrasting
      effects at different hierarchical scales.

PMID- 20149086
TI  - The Casiquiare river acts as a corridor between the Amazonas and Orinoco river
      basins: biogeographic analysis of the genus Cichla.
AB  - The Casiquiare River is a unique biogeographic corridor between the Orinoco and
      Amazonas basins. We investigated the importance of this connection for
      Neotropical fishes using peacock cichlids (Cichla spp.) as a model system. We
      tested whether the Casiquiare provides a conduit for gene flow between
      contemporary populations, and investigated the origin of biogeographic
      distributions that span the Casiquiare. Using sequences from the mitochondrial
      control region of three focal species (C. temensis, C. monoculus, and C.
      orinocensis) whose distributions include the Amazonas, Orinoco, and Casiquiare,
      we constructed maximum likelihood phylograms of haplotypes and analyzed the
      populations under an isolation-with-migration coalescent model. Our analyses
      suggest that populations of all three species have experienced some degree of
      gene flow via the Casiquiare. We also generated a mitochondrial genealogy of all
      Cichla species using >2000 bp and performed a dispersal-vicariance analysis
      (DIVA) to reconstruct the historical biogeography of the genus. This analysis,
      when combined with the intraspecific results, supports two instances of dispersal
      from the Amazonas to the Orinoco. Thus, our results support the idea that the
      Casiquiare connection is important across temporal scales, facilitating both gene
      flow and the dispersal and range expansion of species.

PMID- 20149087
TI  - Restricted dispersal and genetic diversity in populations of an endangered
      montane lizard (Eulamprus leuraensis, Scincidae).
AB  - Many alpine species are under threat from global climate change, as their
      geographic ranges become increasingly fragmented and unsuitable. Understanding
      rates and determinants of gene flow among such fragmented populations, over
      historical as well as recent timescales, can help to identify populations under
      threat. It is also important to clarify the degree to which loss of local
      populations reduces overall genetic diversity within the taxon. The endangered
      Blue Mountains Water Skink (Eulamprus leuraensis) is restricted to <40 small
      swamps in montane south-eastern Australia. Our analyses of seven microsatellite
      loci of 241 animals from 13 populations show strong geographic structure, with
      major genetic divergence even between populations separated by <0.5 km. Dispersal
      between populations is scarce, and appears to involve mostly males. Our analyses
      suggest potential recent bottleneck events in all the identified populations, and
      lower genetic diversity and population size parameter at lower-elevation sites
      than at higher-elevation sites. Management of this endangered taxon thus needs to
      treat most populations separately, because of their genetic distinctiveness and
      low rates of genetic exchange.

PMID- 20149088
TI  - Population structure of wild wheat D-genome progenitor Aegilops tauschii Coss.:
      implications for intraspecific lineage diversification and evolution of common
      wheat.
AB  - Aegilops tauschii Coss. is the D-genome progenitor of hexaploid wheat. Aegilops
      tauschii, a wild diploid species, has a wide natural species range in central
      Eurasia, spreading from Turkey to western China. Amplified fragment length
      polymorphism (AFLP) analysis using a total of 122 accessions of Ae. tauschii was
      conducted to clarify the population structure of this widespread wild wheat
      species. Phylogenetic and principal component analyses revealed two major
      lineages in Ae. tauschii. Bayesian population structure analyses based on the
      AFLP data showed that lineages one (L1) and two (L2) were respectively
      significantly divided into six and three sublineages. Only four out of the six L1
      sublineages were diverged from those of western habitats in the Transcaucasia and
      northern Iran region to eastern habitats such as Pakistan and Afghanistan. Other
      sublineages including L2 were distributed to a limited extent in the western
      region. Subspecies strangulata seemed to be differentiated in one sublineage of
      L2. Among three major haplogroups (HG7, HG9 and HG16) previously identified in
      the Ae. tauschii population based on chloroplast variation, HG7 accessions were
      widely distributed to both L1 and L2, HG9 accessions were restricted to L2, and
      HG16 accessions belonged to L1, suggesting that HG9 and HG16 were formed from HG7
      after divergence of the first two lineages of the nuclear genome. These results
      on the population structure of Ae. tauschii and the genealogical relationship
      among Ae. tauschii accessions should provide important agricultural and
      evolutionary knowledge on genetic resources and conservation of natural genetic
      diversity.

PMID- 20149089
TI  - Coral host transcriptomic states are correlated with Symbiodinium genotypes.
AB  - A mutualistic relationship between reef-building corals and endosymbiotic
      dinoflagellates (Symbiodinium spp.) forms the basis for the existence of coral
      reefs. Genotyping tools for Symbiodinium spp. have added a new level of
      complexity to studies concerning cnidarian growth, nutrient acquisition, and
      stress. For example, the response of the coral holobiont to thermal stress is
      connected to the host-Symbiodinium genotypic combination, as different
      partnerships can have different bleaching susceptibilities. In this study, we
      monitored Symbiodinium physiological parameters and profiled the coral host
      transcriptional responses in acclimated, thermally stressed, and recovered
      fragments of the coral Montastraea faveolata using a custom cDNA gene expression
      microarray. Interestingly, gene expression was more similar among samples with
      the same Symbiodinium content rather than the same experimental condition. In
      order to discount for host-genotypic effects, we sampled fragments from a single
      colony of M. faveolata containing different symbiont types, and found that the
      host transcriptomic states grouped according to Symbiodinium genotype rather than
      thermal stress. As the first study that links coral host transcriptomic patterns
      to the clade content of their Symbiodinium community, our results provide a
      critical step to elucidating the molecular basis of the apparent variability seen
      among different coral-Symbiodinium partnerships.

PMID- 20149090
TI  - Indirect genetic estimates of breeding population size in the polyploid green
      sturgeon (Acipenser medirostris).
AB  - The utility of genetic measures for kinship reconstruction in polysomic species
      is not well evaluated. We developed a framework to test hypotheses about
      estimating breeding population size indirectly from collections of outmigrating
      green sturgeon juveniles. We evaluated a polysomic dataset, in allelic frequency
      and phenotypic formats, from green sturgeon to describe the relationship among
      known progeny from experimental families. The distributions of relatedness values
      for kin classes were used for reconstructing green sturgeon pedigrees from
      juveniles of unknown relationship. We compared three rarefaction functions that
      described the relationship between the number of kin groups and number of samples
      in a pedigree to estimate the annual abundance of spawners contributing to the
      threatened green sturgeon Southern Distinct Population Segment in the upper
      Sacramento River. Results suggested the estimated abundance of breeding green
      sturgeon remained roughly constant in the upper Sacramento River over a 5-year
      period, ranging from 10 to 28 individuals depending on the year and rarefaction
      method. These results demonstrate an empirical understanding for the distribution
      of relatedness values among individuals is a benefit for assessing pedigree
      reconstruction methods and identifying misclassification rates. Monitoring of
      rare species using these indirect methods is feasible and can provide insight
      into breeding and ontogenetic behaviour. While this framework was developed for
      specific application to studying fish populations in a riverscape, the framework
      could be advanced to improve genetic estimation of breeding population size and
      to identify important breeding habitats of rare species when combined with finer
      scaled sampling of offspring.

PMID- 20149092
TI  - Phylogeography of Plathymenia reticulata (Leguminosae) reveals patterns of recent
      range expansion towards northeastern Brazil and southern Cerrados in Eastern
      Tropical South America.
AB  - Little is known about past vegetation dynamics in Eastern Tropical South America
      (ETSA). Here we describe patterns of chloroplast (cp) DNA variation in
      Plathymenia reticulata, a widespread tree in the ETSA Atlantic Forest and Cerrado
      biomes, but not found in the xeromorphic Caatinga. Forty one populations,
      comprising 220 individuals, were analysed by sequencing the trnS-trnG and trnL
      trnL-trnF cpDNA regions. Combined, they resulted in 18 geographically structured
      haplotypes. The central region of the sampling area, comprising Minas Gerais and
      Goias Brazilian states, is a centre of genetic diversity and probably the most
      longstanding area of the distribution range of the species. In contrast,
      populations from northeastern Brazil and the southern Cerrados showed very low
      diversity levels, almost exclusively with common haplotypes which are also found
      in the central region. Coupled with a long-branched star-like network, these
      patterns suggest a recent range expansion of P. reticulata to those regions from
      central region sources. The recent origin of the species (in the early
      Pleistocene) or the extinction of some populations due to drier and cooler
      climate during the last glacial maximum could have been responsible for that
      phylogeographic pattern. The populations from northeastern Brazil originated from
      two colonization routes, one eastern (Atlantic) and one western (inland). Due to
      its high diversity and complex landscape, the central region, especially central
      north Minas Gerais (between 15 degrees -18 degrees S and 42 degrees -46 degrees
      W), should be given the highest priority for conservation.

PMID- 20149091
TI  - Genetic association of physically unlinked islands of genomic divergence in
      incipient species of Anopheles gambiae.
AB  - Previous efforts to uncover the genetic underpinnings of ongoing ecological
      speciation of the M and S forms of the African malaria vector Anopheles gambiae
      revealed two centromere-proximal islands of genetic divergence on X and
      chromosome 2. Under the assumption of considerable ongoing gene flow between M
      and S, these persistently divergent genomic islands were widely considered to be
      'speciation islands'. In the course of microarray-based divergence mapping, we
      discovered a third centromere-associated island of divergence on chromosome 3,
      which was validated by targeted re-sequencing. To test for genetic association
      between the divergence islands on all three chromosomes, SNP-based assays were
      applied in four natural populations of M and S spanning West, Central and East
      Africa. Genotyping of 517 female M and S mosquitoes revealed nearly complete
      linkage disequilibrium between the centromeres of the three independently
      assorting chromosomes. These results suggest that despite the potential for inter
      form gene flow through hybridization, actual (realized) gene flow between M and S
      may be substantially less than commonly assumed and may not explain most shared
      variation. Moreover, the possibility of very low gene flow calls into question
      whether diverged pericentromeric regions-characterized by reduced levels of
      variation and recombination-are in fact instrumental rather than merely
      incidental to the speciation process.

PMID- 20149093
TI  - Geography disentangles introgression from ancestral polymorphism in Lake Malawi
      cichlids.
AB  - Phenotypically diverse Lake Malawi cichlids exhibit similar genomes. The
      extensive sharing of genetic polymorphism among forms has both intrigued and
      frustrated biologists trying to understand the nature of diversity in this and
      other rapidly evolving systems. Shared polymorphism might result from
      hybridization and/or the retention of ancestrally polymorphic alleles. To examine
      these alternatives, we used new genomic tools to characterize genetic
      differentiation in widespread, geographically structured populations of
      Labeotropheus fuelleborni and Metriaclima zebra. These phenotypically distinct
      species share mitochondrial DNA (mtDNA) haplotypes and show greater mtDNA
      differentiation among localities than between species. However, Bayesian analysis
      of nuclear single nucleotide polymorphism (SNP) data revealed two distinct
      genetic clusters corresponding perfectly to morphologically diagnosed L.
      fuelleborni and M. zebra. This result is a function of the resolving power of the
      multi-locus dataset, not a conflict between nuclear and mitochondrial partitions.
      Locus-by-locus analysis showed that mtDNA differentiation between species (F(CT))
      was nearly identical to the median single-locus SNP F(CT). Finally, we asked
      whether there is evidence for gene flow at sites of co-occurrence. We used
      simulations to generate a null distribution for the level of differentiation
      between co-occurring populations of L. fuelleborni and M. zebra expected if there
      was no hybridization. The null hypothesis was rejected for the SNP data;
      populations that co-occur at rock reef sites were slightly more similar than
      expected by chance, suggesting recent gene flow. The coupling of numerous
      independent markers with extensive geographic sampling and simulations utilized
      here provides a framework for assessing the prevalence of gene flow in recently
      diverged species.

PMID- 20149094
TI  - Genome-wide single nucleotide polymorphisms reveal population history and
      adaptive divergence in wild guppies.
AB  - Adaptation of guppies (Poecilia reticulata) to contrasting upland and lowland
      habitats has been extensively studied with respect to behaviour, morphology and
      life history traits. Yet population history has not been studied at the whole
      genome level. Although single nucleotide polymorphisms (SNPs) are the most
      abundant form of variation in many genomes and consequently very informative for
      a genome-wide picture of standing natural variation in populations, genome-wide
      SNP data are rarely available for wild vertebrates. Here we use genetically
      mapped SNP markers to comprehensively survey genetic variation within and among
      naturally occurring guppy populations from a wide geographic range in Trinidad
      and Venezuela. Results from three different clustering methods, Neighbor-net,
      principal component analysis (PCA) and Bayesian analysis show that the population
      substructure agrees with geographic separation and largely with previously
      hypothesized patterns of historical colonization. Within major drainages (Caroni,
      Oropouche and Northern), populations are genetically similar, but those in
      different geographic regions are highly divergent from one another, with some
      indications of ancient shared polymorphisms. Clear genomic signatures of a
      previous introduction experiment were seen, and we detected additional potential
      admixture events. Headwater populations were significantly less heterozygous than
      downstream populations. Pairwise F(ST) values revealed marked differences in
      allele frequencies among populations from different regions, and also among
      populations within the same region. F(ST) outlier methods indicated some regions
      of the genome as being under directional selection. Overall, this study
      demonstrates the power of a genome-wide SNP data set to inform for studies on
      natural variation, adaptation and evolution of wild populations.

PMID- 20149095
TI  - Regional connectivity and coastal expansion: differentiating pre-border and post
      border vectors for the invasive tunicate Styela clava.
AB  - The dramatic increase in marine bio-invasions, particularly of non-indigenous
      ascidians, has highlighted the vulnerability of marine ecosystems and the
      productive sectors that rely on them. A critical issue in managing invasive
      species is determining the relative roles of ongoing introductions, versus the
      local movement of propagules from established source populations. Styela clava
      (Herdman, 1882), the Asian clubbed tunicate, once restricted to the Pacific
      shores of Asia and Russia, is now abundant throughout the northern and southern
      hemispheres and has had significant economic impact in at least one site of
      incursion. In 2005 S. clava was identified in New Zealand. The recent
      introduction of this species, coupled with its restricted distribution, provided
      an ideal model to compare and contrast the introduction and expansion process. In
      this study, the mitochondrial DNA cytochrome oxidase subunit I gene (COI) gene
      and 11 microsatellite markers were used to test the regional genetic structure
      and diversity of 318 S. clava individuals from 10 populations within New Zealand.
      Both markers showed significant differentiation between the northern and southern
      populations, indicative of minimal pre- or post-border connectivity. Additional
      statistics further support pre- and post-border differentiation among Port and
      Harbour populations (i.e. marinas and aquaculture farms). We conclude that New
      Zealand receives multiple introductions, and that the primary vector for pre
      border incursions and post-border spread is most likely the extensive influx of
      recreational vessels that enter northern marinas independent of the Port. This is
      a timely reminder of the potential for hull-fouling organisms to expand their
      range as climates change and open new pathways.

PMID- 20149097
TI  - The earliest stages of adaptation in an experimental plant population: strong
      selection on QTLS for seed dormancy.
AB  - Colonizing species may often encounter strong selection during the initial stages
      of adaptation to novel environments. Such selection is particularly likely to act
      on traits expressed early in development since early survival is necessary for
      the expression of adaptive phenotypes later in life. Genetic studies of fitness
      under field conditions, however, seldom include the earliest developmental
      stages. Using a new set of recombinant inbred lines, we present a study of the
      genetic basis of fitness variation in Arabidopsis thaliana in which genotypes,
      environments, and geographic location were manipulated to study total lifetime
      fitness, beginning with the seed stage. Large-effect quantitative trait loci
      (QTLs) for fitness changed allele frequency and closely approached 90% in some
      treatments within a single generation. These QTLs colocated with QTLs for
      germination phenology when seeds were dispersed following a schedule of a typical
      winter annual, and they were detected in two geographic locations at different
      latitudes. Epistatically interacting loci affected both fitness and germination
      in many cases. QTLs for field germination phenology colocated with known QTLs for
      primary dormancy induction as assessed in laboratory tests, including the
      candidate genes DOG1 and DOG6. Therefore fitness, germination phenology, and
      primary dormancy are genetically associated at the level of specific chromosomal
      regions and candidate loci. Genes associated with the ability to arrest
      development at early life stages and assess environmental conditions are thereby
      likely targets of intense natural selection early in the colonization process.

PMID- 20149098
TI  - On the use of large marker panels to estimate inbreeding and relatedness:
      empirical and simulation studies of a pedigreed zebra finch population typed at
      771 SNPs.
AB  - In recent years there has been a dramatic increase in the availability of high
      density genetic marker data for both model and non-model organisms. A potential
      application of these data is to infer relatedness in the absence of a complete
      pedigree. Using a marker panel of 771 SNPs genotyped in three generations of an
      extensive zebra finch pedigree, correlations between pedigree relatedness and
      seven marker-based estimates of relatedness were examined, as was the
      relationship between heterozygosity and inbreeding. Although marker-based and
      pedigree relatedness were highly correlated, the variance in estimated
      relatedness was high. Further, the correlation between heterozygosity and
      inbreeding was weak, even though mean inbreeding coefficient is typical of that
      seen in wild vertebrate pedigrees; the weak relationship was in part due to the
      small variance in inbreeding in the pedigree. Our data suggest that using marker
      information to reconstruct the pedigree, and then calculating relatedness from
      the pedigree, is likely to give more accurate relatedness estimates than using
      marker-based estimators directly.

PMID- 20149099
TI  - Adjusting to alien genes.
AB  - From the perspective of a bacterium, higher eukaryotes are oversexed,
      unadventurous and reproduce in an inconvenient way. Sex, or recombination
      following horizontal gene transfer (HGT) events, to be less provocative, is a
      rare event for a bacterium, but a potentially profound one. Through HGT a
      bacterium can acquire DNA from distant as well as closely related species and,
      thereby, instantly obtain genes that encode novel functions or replace its
      existing genes with better ones. While there is an abundance of retrospective
      evidence for HGT in bacteria, there has been little consideration of the dynamics
      of the process. In this issue of Molecular Microbiology Lind et al. explore these
      dynamics theoretically, and then experimentally by substituting Salmonella
      Typhimurium ribosomal genes with orthologues from various microbial origins. The
      authors show that the majority of these newly acquired ribosomal proteins reduce
      fitness in S. Typhimurium, but within short order (40-250 generations) subsequent
      evolution will mitigate the fitness costs of the alien alleles. The presented
      results suggest that that at least the initial phase of adapting to alien genes
      of this informational core ilk is not by changing them but rather by increasing
      their level of expression by gene amplification. Lind et al. argue that their
      results provide an explanation as to why duplicated genes are overrepresented
      among horizontally transferred genes.

PMID- 20149100
TI  - Two sources of endogenous hydrogen peroxide in Escherichia coli.
AB  - Mechanisms of hydrogen peroxide generation in Escherichia coli were investigated
      using a strain lacking scavenging enzymes. Surprisingly, the deletion of many
      abundant flavoenzymes that are known to autoxidize in vitro did not substantially
      lessen overall H(2)O(2) formation. However, H(2)O(2) production diminished by 25
      30% when NadB turnover was eliminated. The flavin-dependent desaturating
      dehydrogenase, NadB uses fumarate as an electron acceptor in anaerobic cells.
      Experiments showed that aerobic NadB turnover depends upon its oxidation by
      molecular oxygen, with H(2)O(2) as a product. This reaction appears to be
      mechanistically adventitious. In contrast, most desaturating dehydrogenases are
      associated with the respiratory chain and deliver electrons to fumarate
      anaerobically or oxygen aerobically without the formation of toxic by-products.
      Presumably, NadB can persist as an H(2)O(2)-generating enzyme because its flux is
      limited. The anaerobic respiratory enzyme fumarate reductase uses a flavoprotein
      subunit that is homologous to NadB and accordingly forms substantial H(2)O(2)
      upon aeration. This tendency is substantially suppressed by cytochrome oxidase.
      Thus cytochrome d oxidase, which is prevalent among anaerobes, may diminish
      intracellular H(2)O(2) formation by the anaerobic respiratory chain, whenever
      these organisms encounter oxygen. These two examples reveal biochemical and
      physiological arrangements through which evolution has minimized the rate of
      intracellular oxidant formation.

PMID- 20149101
TI  - The conserved and divergent roles of carbonic anhydrases in the filamentous fungi
      Aspergillus fumigatus and Aspergillus nidulans.
AB  - Carbon dioxide (CO(2)) and its hydration product bicarbonate (HCO(3)(-)) are
      essential molecules in various physiological processes of all living organisms.
      The reversible interconversion between CO(2) and HCO(3)(-) is in equilibrium.
      This reaction is slow without catalyst, but can be rapidly facilitated by Zn(2+)
      metalloenzymes named carbonic anhydrases (CAs). To gain an insight into the
      function of multiple clades of fungal CA, we chose to investigate the filamentous
      fungi Aspergillus fumigatus and A. nidulans. We identified four and two CAs in A.
      fumigatus and A. nidulans, respectively, named cafA-D and canA-B. The cafA and
      cafB genes are constitutively, strongly expressed whereas cafC and cafD genes are
      weakly expressed but CO(2)-inducible. Heterologous expression of the A. fumigatus
      cafB, and A. nidulans canA and canB genes completely rescued the high CO(2)
      requiring phenotype of a Saccharomyces cerevisiae Deltance103 mutant. Only the
      DeltacafA DeltacafB and DeltacanB deletion mutants were unable to grow at 0.033%
      CO(2), of which growth defects can be restored by high CO(2). Defects in the CAs
      can affect Aspergilli conidiation. Furthermore, A. fumigatus DeltacafA,
      DeltacafB, DeltacafC, DeltacafD and DeltacafA DeltacafB mutant strains are fully
      virulent in a low-dose murine infection.

PMID- 20149102
TI  - AglP is a S-adenosyl-L-methionine-dependent methyltransferase that participates
      in the N-glycosylation pathway of Haloferax volcanii.
AB  - While pathways for N-glycosylation in Eukarya and Bacteria have been solved,
      considerably less is known of this post-translational modification in Archaea. In
      the halophilic archaeon Haloferax volcanii, proteins encoded by the agl genes are
      involved in the assembly and attachment of a pentasaccharide to select asparagine
      residues of the S-layer glycoprotein. AglP, originally identified based on the
      proximity of its encoding gene to other agl genes whose products were shown to
      participate in N-glycosylation, was proposed, based on sequence homology, to
      serve as a methyltransferase. In the present report, gene deletion and mass
      spectrometry were employed to reveal that AglP is responsible for adding a 14 Da
      moiety to a hexuronic acid found at position four of the pentasaccharide
      decorating the Hfx. volcanii S-layer glycoprotein. Subsequent purification of a
      tagged version of AglP and development of an in vitro assay to test the function
      of the protein confirmed that AglP is a S-adenosyl-L-methionine-dependent
      methyltransferase.

PMID- 20149103
TI  - Caulobacter PopZ forms a polar subdomain dictating sequential changes in pole
      composition and function.
AB  - The bacterium Caulobacter crescentus has morphologically and functionally
      distinct cell poles that undergo sequential changes during the cell cycle. We
      show that the PopZ oligomeric network forms polar ribosome exclusion zones that
      change function during cell cycle progression. The parS/ParB chromosomal
      centromere is tethered to PopZ at one pole prior to the initiation of DNA
      replication. During polar maturation, the PopZ-centromere tether is broken, and
      the PopZ zone at that pole then switches function to act as a recruitment factor
      for the ordered addition of multiple proteins that promote the transformation of
      the flagellated pole into a stalked pole. Stalked pole assembly, in turn,
      triggers the initiation of chromosome replication, which signals the formation of
      a new PopZ zone at the opposite cell pole, where it functions to anchor the newly
      duplicated centromere that has traversed the long axis of the cell. We propose
      that pole-specific control of PopZ function co-ordinates polar development and
      cell cycle progression by enabling independent assembly and tethering activities
      at the two cell poles.

PMID- 20149104
TI  - Estimating Z-ring radius and contraction in dividing Escherichia coli.
AB  - We present a fluorescence recovery after photobleaching-based method for
      monitoring the progression of septal Z-ring contraction in dividing Escherichia
      coli cells. In a large number of cells undergoing division, we irreversibly
      bleached cytosolically expressed Enhanced Green Fluorescent Protein on one side
      of the septal invagination and followed the fluorescence relaxation on both sides
      of the septum. Since the relaxation time depends on the cross-sectional area of
      the septum, it can be used to determine the septal radius r. Assuming that the
      fraction of the observed cells with r-values in a given interval reflects the
      duration of that interval in the division process we could derive an approximate
      time-course for the contraction event, as a population average. By applying the
      method repeatedly on individual cells, the contraction process was also followed
      in real time. On a population average level, our data are best described by a
      linear contraction process in time. However, on the single cell level the
      contraction processes display a complex behaviour, with varying levels of
      activity. The proposed approach provides a simple yet versatile method for
      studying Z-ring contraction in vivo, and will help to elucidate its underlying
      mechanisms.

PMID- 20149106
TI  - Identification of the gate regions in the primary structure of the secretin pIV.
AB  - Secretins are a family of large bacterial outer membrane channels that serve as
      exit ports for folded proteins, filamentous phage and surface structures. Despite
      the large size of their substrates, secretins do not compromise the barrier
      function of the outer membrane, implying a gating mechanism. The region in the
      primary structure that forms the putative gate has not previously been determined
      for any secretin. To identify residues involved in gating the pIV secretin of
      filamentous bacteriophage f1, we used random mutagenesis of the gene followed by
      positive selection for mutants with compromised barrier function ('leaky'
      mutants). We identified mutations in 34 residues, 30 of which were clustered into
      two regions located in the centre of the conserved C-terminal secretin family
      domain: GATE1 (that spanned 39 residues) and GATE2 (that spanned 14 residues). An
      internal deletion constructed in the GATE2 region resulted in a severely leaky
      phenotype. Three of the four remaining mutations are located in the region that
      encodes the N-terminal, periplasmic portion of pIV and could be involved in
      triggering gate opening. Two missense mutations in the 24-residue region that
      separates GATE1 and GATE2 were also constructed. These mutant proteins were
      unstable, defective in multimerization and non-functional.

PMID- 20149105
TI  - Update on Legionnaires' disease: pathogenesis, epidemiology, detection and
      control.
AB  - Legionellosis or Legionnaires' disease is an emerging and often-fatal form of
      pneumonia that is most severe in elderly and immunocompromised people, an ever
      increasing risk group for infection. In recent years, the genomics of Legionella
      spp. has significantly increased our knowledge of the pathogenesis of this
      disease by providing new insights into the evolution and genetic and
      physiological basis of Legionella-host interactions. The seventh international
      conference on Legionella, Legionella 2009, illustrated many recent conceptual
      advances in epidemiology, pathogenesis and ecology. Experts in different fields
      presented new findings on basic mechanisms of pathogen-host interactions and
      bacterial evolution, as well as the clinical management and environmental
      prevalence and persistence of Legionella. The presentations revealed remarkable
      facts about the genetic and metabolic basis of the intracellular lifestyle of
      Legionella and reported on its striking ability to manipulate host cell processes
      by molecular mimicry. Together, these investigations will lead to new approaches
      for the treatment and prevention of Legionnaires' disease.

PMID- 20149107
TI  - Discovery of an operon that participates in agmatine metabolism and regulates
      biofilm formation in Pseudomonas aeruginosa.
AB  - Agmatine is the decarboxylation product of arginine and a number of bacteria have
      devoted enzymatic pathways for its metabolism. Pseudomonas aeruginosa harbours
      the aguBA operon that metabolizes agmatine to putrescine, which can be
      subsequently converted into other polyamines or shunted into the TCA cycle for
      energy production. We discovered an alternate agmatine operon in the P.
      aeruginosa strain PA14 named agu2ABCA' that contains two genes for agmatine
      deiminases (agu2A and agu2A'). This operon was found to be present in 25% of
      clinical P. aeruginosa isolates. Agu2A' contains a twin-arginine translocation
      signal at its N-terminus and site-directed mutagenesis and cell fractionation
      experiments confirmed this protein is secreted to the periplasm. Analysis of the
      agu2ABCA' promoter demonstrates that agmatine induces expression of the operon
      during the stationary phase of growth and during biofilm growth and agu2ABCA'
      provides only weak complementation of aguBA, which is induced during log phase.
      Biofilm assays of mutants of all three agmatine deiminase genes in PA14 revealed
      that deletion of agu2ABCA', specifically its secreted product Agu2A', reduces
      biofilm production of PA14 following addition of exogenous agmatine. Together,
      these findings reveal a novel role for the agu2ABCA' operon in the biofilm
      development of P. aeruginosa.

PMID- 20149108
TI  - Distinct subcellular localization in the cytosol and apicoplast, unexpected
      dimerization and inhibition of Plasmodium falciparum glyoxalases.
AB  - The ubiquitous glyoxalase system removes methylglyoxal as a harmful by-product of
      glycolysis. Because malaria parasites have drastically increased glycolytic
      fluxes, they could be highly susceptible to the inhibition of this detoxification
      pathway. Here we analysed the intracellular localization, oligomerization and
      inhibition of the glyoxalases from Plasmodium falciparum. Glyoxalase I (GloI) and
      one of the two glyoxalases II (cGloII) were located in the cytosol of the blood
      stages. The second glyoxalase II (tGloII) was detected in the apicoplast pointing
      to alternative metabolic pathways. Using a variety of methods, cGloII was found
      to exist in a monomer-dimer equilibrium that might have been overlooked for
      homologues from other organisms and that could be of physiological importance.
      The compounds methyl-gerfelin and curcumin, which were previously shown to
      inhibit mammalian GloI, also inhibited P. falciparum GloI. Inhibition patterns
      were predominantly competitive but were complicated because of the two different
      active sites of the enzyme. This effect was neglected in previous inhibition
      studies of monomeric glyoxalases I, with consequences for the interpretation of
      inhibition constants. In summary, the present work reveals novel general
      glyoxalase properties that future research can build on and provides a
      significant advance in characterizing the glyoxalase system from P. falciparum.

PMID- 20149110
TI  - From signal perception to signal transduction: ligand-induced dimeric switch of
      DctB sensory domain in solution.
AB  - Sinorhizobium meliloti DctB is a typical transmembrane sensory histidine kinase,
      which senses C(4)-dicarboxylic acids (DCA) and regulates the expression of DctA,
      the DCA transporter. We previously reported the crystal structures of its
      periplasmic sensory domain (DctBp) in apo and succinate-bound states, and these
      structures showed dramatic conformational changes at dimeric level. Here we show
      a ligand-induced dimeric switch in solution and a strong correlation between
      DctBp's dimerization states and the in vivo activities of DctB. Using site
      directed mutagenesis, we identify important determinants for signal perception
      and transduction. Specifically, we show that the ligand-binding pocket is
      essential for DCA-induced 'on' activity of DctB. Mutations at different sections
      of DctBp's dimerization interface can lock full-length DctB at either 'on' or
      'off' state, independent of ligand binding. Taken together, these results suggest
      that DctBp's signal perception and transduction occur through a 'ligand-induced
      dimeric switch', in which the changes in the dimeric conformations upon ligand
      binding are responsible for the signal transduction in DctB.

PMID- 20149111
TI  - Stress-induced barrier disruption of rat follicle-associated epithelium involves
      corticotropin-releasing hormone, acetylcholine, substance P, and mast cells.
AB  - BACKGROUND: The follicle-associated epithelium (FAE) is specialized in uptake and
      sampling of luminal antigens and bacteria. We previously showed that stress
      increased FAE permeability in rats. An increased uptake may alter antigen
      exposure in Peyer's patches leading to intestinal disease. The aim of this study
      was to elucidate mechanisms involved in the acute stress-induced increase in FAE
      permeability. METHODS: Rats were pretreated i.p. with corticotropin-releasing
      hormone receptor (CRH-R) antagonist, neurokinin receptor 1 (NK-1R) antagonist,
      atropine, the mast cell stabilizer doxantrazole (DOX), or NaCl, and submitted to
      1-h acute water avoidance stress. FAE tissues were mounted in Ussing chambers for
      measurements of permeability to (51)Cr-EDTA, horseradish peroxidase (HRP) and
      chemically killed Escherichia coli K-12. Further, FAE segments were exposed in
      vitro in chambers to CRH, substance P (SP), carbachol, and DOX. Neurotransmitter-
      and receptor distribution was studied by immunohistochemistry. KEY RESULTS:
      Stress-induced increases in uptake across FAE of HRP and E. coli were reduced by
      DOX, CRH-R antagonist and atropine, whereas the NK-1R antagonist decreased (51)Cr
      EDTA permeability. Exposure to CRH and carbachol increased HRP and E. coli
      passage, whereas SP increased bacterial and (51)Cr-EDTA permeability. DOX
      counteracted all of these effects. Immunohistochemistry revealed CRH,
      acetylcholine, SP, and their receptors on mast cells within the Peyer's patches,
      subepithelial dome, and adjacent villi. CONCLUSIONS & INFERENCES: Corticotropin
      releasing hormone and acetylcholine signaling affect mainly transcellular
      permeability while SP seems more selective toward the paracellular pathways. Our
      findings may be of importance for the understanding of the pathogenesis of stress
      related intestinal disorders.

PMID- 20149109
TI  - A high-affinity putrescine-cadaverine transporter from Trypanosoma cruzi.
AB  - Whereas mammalian cells and most other organisms can synthesize polyamines from
      basic amino acids, the protozoan parasite Trypanosoma cruzi is incapable of
      polyamine biosynthesis de novo and therefore obligatorily relies upon putrescine
      acquisition from the host to meet its nutritional requirements. The cell surface
      proteins that mediate polyamine transport into T. cruzi, as well as most
      eukaryotes, however, have by-in-large eluded discovery at the molecular level.
      Here we report the identification and functional characterization of two
      polyamine transporters, TcPOT1.1 and TcPOT1.2, encoded by alleles from two T.
      cruzi haplotypes. Overexpression of the TcPOT1.1 and TcPOT1.2 genes in T. cruzi
      epimastigotes revealed that TcPOT1.1 and TcPOT1.2 were high-affinity transporters
      that recognized both putrescine and cadaverine but not spermidine or spermine.
      Furthermore, the activities and subcellular locations of both TcPOT1.1 and
      TcPOT1.2 in intact parasites were profoundly influenced by extracellular
      putrescine availability. These results establish TcPOT1.1 and TcPOT1.2 as key
      components of the T. cruzi polyamine transport pathway, an indispensable
      nutritional function for the parasite that may be amenable to therapeutic
      manipulation.

PMID- 20149112
TI  - MYB96-mediated abscisic acid signals induce pathogen resistance response by
      promoting salicylic acid biosynthesis in Arabidopsis.
AB  - *The Arabidopsis MYB96 transcription factor plays a role in abscisic acid (ABA)
      mediated drought response. Notably, anthocyanins accumulate in the activation
      tagging myb96-1d line, suggesting a role of MYB96 in biotic and abiotic stress
      responses in plants. Here, we investigate the role of MYB96 in salicylic acid
      (SA) biosynthesis and plant defense and explore the mechanisms underlying the ABA
      SA interaction. *myb96-1d and myb96-1 were subject to pathogen infection assays,
      and expression of SA biosynthetic and defense genes was examined. myb96-1d was
      crossed with the NahG transgenic plants to investigate the role of MYB96 in ABA
      regulation of SA biosynthesis. *Whereas myb96-1d exhibited an enhanced disease
      resistance, myb96-1 was susceptible to pathogen infection. A subset of
      pathogenesis-related (PR) genes was up-regulated in myb96-1d. However, PR
      transcript abundances were reduced in myb96-1d X NahG. Interestingly, a SA
      biosynthetic gene SALICYLIC ACID INDUCTION DEFICIENT2 (SID2) was up-regulated,
      and concentrations of SA and SA-beta-glucoside (SAG) were elevated in myb96-1d.
      In addition, the inductive effects of abiotic stresses on SID2 were reduced in
      aba3-1. *Our observations indicate that MYB96-mediated ABA signals enhance plant
      disease resistance by inducing SA biosynthesis. It is envisioned that MYB96 is a
      molecular link that mediates ABA-SA crosstalks.

PMID- 20149113
TI  - The first meiosis of resynthesized Brassica napus, a genome blender.
AB  - Polyploidy promotes the restructuring of merged genomes within initial
      generations of resynthesized Brassica napus, possibly caused by homoeologous
      recombination at meiosis. However, little is known about the impact of the first
      confrontation of two genomes at the first meiosis which could lead to genome
      exchanges in progeny. Here, we assessed the role of the first meiosis in the
      genome instability of synthetic B. napus. We used three different newly
      resynthesized B. napus plants and established meiotic pairing frequencies for the
      A and C genomes. We genotyped the three corresponding progenies in a cross to a
      natural B. napus on the two homoeologous A1 and C1 chromosomes. Pairing at
      meiosis in a set of progenies with various rearrangements was scored. Here, we
      confirmed that the very first meiosis of resynthesized plants of B. napus acts as
      a genome blender, with many of the meiotic-driven genetic changes transmitted to
      the progenies, in proportions that depend significantly on the cytoplasm
      background inherited from the progenitors. We conclude that the first meiosis
      generates rearrangements on both genomes and promotes subsequent restructuring in
      further generations. Our study advances the knowledge on the timing of genetic
      changes and the mechanisms that may bias their transmission.

PMID- 20149114
TI  - Transcriptomic changes following recent natural hybridization and allopolyploidy
      in the salt marsh species Spartina x townsendii and Spartina anglica (Poaceae).
AB  - Allopolyploidy results from two events: the merger of divergent genomes and
      genome duplication. Both events have important functional consequences for the
      evolution and adaptation of newly formed allopolyploid species. In spite of the
      significant progress made in recent years, few studies have decoupled the effects
      of hybridization from genome duplication in the observed patterns of expression
      changes accompanying allopolyploidy in natural conditions. We used Agilent rice
      oligomicroarrays to explore gene expression changes following allopolyploidy in
      Spartina that includes a classic example of recent allopolyploid speciation: S.
      anglica formed during the 19th century following genome duplication of the hybrid
      S. x townsendii. Our data indicate important, but different, effects of
      hybridization and genome duplication in the expression patterns of the hybrid and
      allopolyploid. Deviation from parental additivity was most important following
      hybridization and was accompanied by maternal expression dominance, although
      transgressively expressed genes were also encountered. Maternal dominance was
      attenuated following genome duplication in S. anglica, but this species exhibits
      an increased number of transgressively overexpressed genes. These results reflect
      the decoupled effects of the 'genomic shock' following hybridization and genome
      redundancy on the genetic, epigenetic and regulatory mechanisms characterizing
      transcriptomic evolution in allopolyploids.

PMID- 20149115
TI  - The signalling peptide EPFL9 is a positive regulator of stomatal development.
AB  - The putative secretory peptides epidermal patterning factor 1 (EPF1) and EPF2 act
      as negative regulators of stomatal clustering and density early in Arabidopsis
      leaf development. Here, we investigated whether the related peptide gene
      epidermal patterning factor-like 9 (EPFL9), which is coexpressed with EPF1 and
      stomatal density and distribution 1 (SDD1), also plays a role in controlling
      stomatal development. Plants manipulated to constitutively overexpress EPFL9
      showed increased stomatal density and clustering, and those manipulated to have
      reduced EPFL9 expression showed reduced stomatal density with no clustering,
      confirming that EPFL9 is a regulator of stomatal development. Genetic analysis
      was consistent with EPFL9 acting independently of EPF1 to control stomatal
      clustering, independently of EPF2 to regulate stomatal density, and independently
      of SDD1 to control both stomatal clustering and density. These findings
      demonstrate that at least three secretory peptides independently regulate
      stomatal development. Surprisingly, EPFL9 acts to increase, rather than decrease,
      stomatal density and clustering. However, in common with EPF1 and EPF2, EPFL9 is
      unlikely to be a substrate for proteolysis by SDD1.

PMID- 20149116
TI  - Newly synthesized wheat allohexaploids display progenitor-dependent meiotic
      stability and aneuploidy but structural genomic additivity.
AB  - To understand key mechanisms leading to stabilized allopolyploid species, we
      characterized the meiotic behaviour of wheat allohexaploids in relation to
      structural and genetic changes. For that purpose, we analysed first generations
      of synthetic allohexaploids obtained through interspecific hybridization,
      followed by spontaneous chromosome doubling, between several genotypes of
      Triticum turgidum and Aegilops tauschii wheat species, donors of AB and D
      genomes, respectively. As expected for these Ph1 (Pairing homoeologous 1) gene
      carrying allopolyploids, chromosome pairing at metaphase I of meiosis essentially
      occurs between homologous chromosomes. However, the different synthetic
      allohexaploids exhibited progenitor-dependent meiotic irregularities, such as
      incomplete homologous pairing, resulting in univalent formation and leading to
      aneuploidy in the subsequent generation. Stability of the synthetic
      allohexaploids was shown to depend on the considered genotypes of both AB and D
      genome progenitors, where few combinations compare to the natural wheat
      allohexaploid in terms of regularity of meiosis and euploidy. Aneuploidy
      represents the only structural change observed in these synthetic allohexaploids,
      as no apparent DNA sequence elimination or rearrangement was observed when
      analysing euploid plants with molecular markers, developed from expressed
      sequence tags (ESTs) as well as simple sequence repeat (SSR) and transposable
      element sequences.

PMID- 20149117
TI  - Intelligence and obesity: does the intensity of mental workload matter?

PMID- 20149118
TI  - A systematic review of fast food access studies.
AB  - The frequent consumption of energy-dense fast food is associated with increased
      body mass index. This systematic review aims to examine the methodology and
      current evidence on fast food access and its associations with outcomes. Six
      databases were searched using terms relating to fast food. Only peer-reviewed
      studies published in English during a 10-year period, with data collection and
      analysis regarding fast food access were included. Forty articles met the
      aforementioned criteria. Nearly half of the studies (n = 16) used their own set
      of features to define fast food. Studies predominantly examined the relationship
      between fast food access and socioeconomic factors (n = 21) and 76% indicated
      fast food restaurants were more prevalent in low-income areas compared with
      middle- to higher-income areas. Ten of 12 studies found fast food restaurants
      were more prevalent in areas with higher concentrations of ethnic minority groups
      in comparison with Caucasians. Six adult studies found higher body mass index was
      associated with living in areas with increased exposure to fast food; four
      studies, however, did not find associations. Further work is needed to understand
      if and how fast food access impacts dietary intake and health outcomes; and if
      fast food access has disparate socioeconomic, race/ethnicity and age
      associations.

PMID- 20149119
TI  - Leptin and gastro-intestinal malignancies.
AB  - Obesity is a well-established risk factor for the development and mortality from
      several cancers, including adenocarcinoma of the oesophagus, oesophago-gastric
      junction and colorectum. Despite a large body of epidemiological evidence
      describing this relationship, the mechanisms relating obesity and cancer are only
      starting to be uncovered. The altered secretion of metabolically active, pro
      inflammatory adipocytokines from adipose tissue is believed to play a key role,
      and leptin is believed to be a key player in obesity-related carcinogenesis, as
      well as being the most extensively studied of the adipokines. In this literature
      review, we aim to examine the association between leptin and cancers of the
      gastro-intestinal tract. For each individual cancer, we examine and present the
      published data examining the role of leptin in both cell and animal models, the
      association between circulating leptin levels and cancer risk, and finally the
      expression of the leptin system in human gastro-intestinal tract tumours, in
      relation to tumour biology, stage and patient outcome.

PMID- 20149120
TI  - Systematic review of the effectiveness of weight management schemes for the under
      fives.
AB  - Overweight and obesity in pre-school children are an increasing problem, with
      poor diet and exercise habits laying the foundation for serious health risks in
      later life. Yet most research into childhood obesity has focused on school-age
      children. Two previous systematic reviews of pre-school children have included
      uncontrolled designs and self-report outcomes potentially biasing the results in
      favour of the interventions. We have conducted a systematic review of the
      effectiveness and cost-effectiveness of weight management schemes for the under
      fives restricting the inclusion criteria to controlled trials with objective
      measures. We found four effectiveness randomized controlled trials of prevention.
      No treatment or cost-effectiveness studies were found. Only one study in a Latino
      community showed a statistically significant advantage from the intervention in a
      slower rate of increase in body mass index. However, trends in decrease in body
      mass index and weight loss favoured the intervention groups in other studies.
      From the studies characteristics we hypothesize that important features to
      include in future interventions may be; cultural sensitivity, sustained moderate
      to vigorous exercise, active engagement of the parents in the programme and as
      role models of healthy living and active engagement of the children in nutrition
      education. Further randomized controlled trials are needed in this population.

PMID- 20149121
TI  - ICD therapy in children and young adults: low incidence of inappropriate shock
      delivery.
AB  - INTRODUCTION: Implantable cardioverter defibrillator (ICD) therapy of life
      threatening arrhythmias in pediatric patients is feasible; however, recent
      studies report a high incidence of inappropriate shock deliveries. METHODS: The
      data of all recipients of an ICD at the Charite, Department of Pediatric
      Cardiology, between January 2001 and November 2007 were retrospectively analyzed
      regarding underlying cardiac disorders, arrhythmias, medication, ablation
      procedures, leads and devices, programming, and ICD therapies. RESULTS: A total
      of 33 patients underwent ICD implantation, with a median age of 16.5 years (range
      8-36 years) and a mean weight of 61 +/- 20.9 kg. Underlying cardiac disorders
      were electrical heart disease (27%), cardiomyopathy (30%), congenital heart
      disease (33%), and others (9%). Eighty-five percent received antiarrhythmic
      drugs, and 12 ablation procedures were performed in nine patients (27%). The
      devices were programmed individually according to the underlying diseases and
      arrhythmias. During follow-up, a total of 63 shock therapies were delivered in 11
      patients, while a majority of 34 shocks occurred in one patient (no therapies in
      22 of 33 patients). Only two such therapies were inappropriate, both delivered
      for atrial flutter. CONCLUSIONS: In children and young adults receiving ICD
      therapy, the combination of strategies to prevent ventricular arrhythmias using
      specific drug therapy, ablation procedures, and individual programming with
      improved devices and leads causes a low incidence of inappropriate shock
      delivery.

PMID- 20149122
TI  - Correlates of glycemic control and quality of life outcomes in adolescents with
      type 1 diabetes.
AB  - BACKGROUND: A major focus of pediatric multidisciplinary diabetes care is
      promoting glycemic control (A1c) while ensuring high quality of life (QOL). The
      current study investigated factors associated with A1c and QOL using a
      methodology that considered these variables as simultaneous outcomes. METHOD: A
      total of 261 adolescents (aged 13-18) with type 1 diabetes completed measures of
      blood glucose monitoring (BGM) frequency, diabetes-specific QOL, negative affect,
      and depression. Caregivers completed measures of demographic and disease
      characteristics, depression, and family conflict. RESULTS: A1c was negatively
      correlated with QOL (r = -0.18 to -0.29, p < 0.01) across all subscales. Based on
      clinical A1c goals and median QOL scores, adolescents fell into four glycemic
      control-QOL groups. Multinomial logistic regression determined correlates of
      group membership utilizing adolescents with suboptimal glycemic control-low QOL
      as the referent group. Adolescents with optimal glycemic control-high QOL
      reported increased BGM frequency (OR = 1.87), less negative affect (OR = 1.32),
      and were more likely to use CSII (OR = 5.41). Adolescents with optimal A1c-low
      QOL reported greater BGM frequency (OR = 1.91) and shorter disease duration (OR =
      1.09). Adolescents with suboptimal glycemic control-high QOL reported greater BGM
      frequency (OR = 1.41), fewer depressive symptoms (OR = 1.13), and less negative
      affect (OR = 1.31). CONCLUSIONS: Results reveal disease, management, and
      psychosocial characteristics that differentiate glycemic control-QOL outcome
      groups and identify risk factors related to this relationship. Further
      appreciation of these characteristics may increase clinicians' understanding and
      attention to these important clinical outcomes and help tailor the most
      appropriate interventions (e.g., individual psychotherapy vs. family problem
      solving interventions) to help adolescents achieve glycemic control without
      sacrificing QOL.

PMID- 20149123
TI  - Low prevalence of glucose intolerance in racially mixed children with cystic
      fibrosis.
AB  - OBJECTIVE: To evaluate glucose tolerance in racially mixed Brazilian youth with
      cystic fibrosis (CF). METHODS: Cross-sectional study conducted between August and
      September 2007, at a reference service for CF, evaluating: glycated hemoglobin
      (HbA1c), blood glucose, and insulin levels, before and 2 h after a glucose
      overload. RESULTS: There were 46 patients aged between 6 yr and 16 yr and 2
      months (median: 9 yr and 10 months) of whom 64% were boys. Of these, 26% were
      Whites; 54.4% Mulattoes; and 19.6% Blacks. HbA1c was normal in all patients. Only
      one participant (12-yr old) had glucose intolerance. Insulin levels ranged from 1
      to 23 uIU/mL (median: 4.5 uIU/mL) at baseline and from 3.2 to 192.1 uIU/mL
      (median: 11 uIU/mL) after a glucose overload. Insulin resistance evaluated by the
      HOMA index, stratified by sex and age, was present in three patients. The
      DeltaF508 mutation was present in only 4.3% of the sample, all of them being
      heterozygous. CONCLUSIONS: The low prevalence of carbohydrate intolerance in this
      population is probably a result of their young age. Another possibility is the
      low frequency of the DeltaF508 mutation. Although not conclusive, these data
      suggest that in addition to age, the genotype:phenotype ratio may influence the
      development of glucose intolerance in patients with CF.

PMID- 20149124
TI  - Hemoglobin A1c is a reliable criterion for diagnosing type 1 diabetes in
      childhood and adolescence.
AB  - BACKGROUND: Little is known about the use of the hemoglobin A1C (HbA1c) test for
      the diagnosis of diabetes in childhood and adolescence. The aim is to investigate
      sensitivity and specificity of HbA1c at onset of childhood type 1 diabetes.
      METHODS: A total of 184 children and adolescents with blood glucose levels above
      200 mg/dL (11.1 mmol/L) were included: 84.8% (n = 156, mean age 9.0 yr) with new
      onset of type 1 diabetes, 15.2% (n = 28, mean age 6.1 yr) with transient
      hyperglycemia. HbA1c was measured using the Bayer((r)) DCA2000 analyzer. RESULTS:
      Patients with new onset of type 1 diabetes (n = 156) had HbA1c values between
      6.6% and > 14% (mean (SD) 11.4 (2.0)%; IQR, interquartile range 9.8-13.3%). All
      patients suffered from typical symptoms of hyperglycemia, i.e., polyuria and
      polydipsia. In the patient group with transient hyperglycemia (n = 28), HbA1c
      values were between 4.5 and 6.1% (mean (SD) 5.3 (0.4)%; IQR 5.0-5.6%). None of
      these patients reported typical symptoms of diabetes. All patients with HbA1c
      values greater than 6.35% had new onset of type 1 diabetes. Sensitivity of HbA1c
      at the onset of childhood type 1 diabetes was calculated to be 100%. In patients
      with HbA1c values less than 6.35%, the diagnosis of type 1 diabetes could be
      excluded. Thus, specificity of HbA1c as diagnostic criterion was 100%.
      CONCLUSIONS: Childhood type 1 diabetes can be diagnosed and excluded with high
      reliability by means of HbA1c testing.

PMID- 20149125
TI  - Pediatric condition falsification (Munchausen syndrome by Proxy) as a continuum
      of maternal factitious disorder (Munchausen syndrome).
AB  - Pediatric condition falsification (PCF), also known as Munchausen syndrome by
      Proxy or Medical Child Abuse, is a somewhat rare form of child abuse and neglect.
      Its association with a history of adult factitious disorder (AFD) or Munchausen
      syndrome in the perpetrator is also well known. Exogenous insulin injection to
      cause hypoglycemia both in the context of PCF and AFD has been reported in the
      literature. However, the coexistence of both conditions via insulin injection in
      the same family has not been reported in the literature. This paper presents a
      family, in which the mother was diagnosed with AFD and her three children with
      PCF perpetrated by their mother via exogenous insulin injection.

PMID- 20149126
TI  - Efficacy and safety of linezolid in immunocompromised children with cancer.
AB  - BACKGROUND: The aim of this study was to determine the safety, tolerance and
      efficacy of linezolid for the treatment of infections from Gram-positive bacteria
      in immunocompromised children with cancer. METHODS: This was a prospective non
      comparative unblinded study in the Hematology/Oncology Unit over a two-year
      period, administering linezolid as monotherapy in children with cancer. RESULTS:
      Seventeen children received linezolid (30 mg/kgr: 3 i.v. per day). Mean duration
      of linezolid administration was 12.2 days (range, 6-38 days), while the median
      age of the evaluable patients was 2.2 years (range, 6 months-11.2 years). Primary
      diagnosis was acute lymphoblastic leukemia (nine patients), brain tumor (three
      patients), multi-organ Langerhans cell histiocytosis (two patients),
      rhabdomyosarcoma, Burkitt's lymphoma and ovarian tumor (one patient each). All
      patients were in the midst of chemotherapy cycles. Ten out of 17 children had
      positive blood cultures (methicillin-resistant Staphylococcus aureus, four
      patients; vancomycin-resistant Enterococcus, three patients; penicillin-resistant
      Streptococcus pneumoniae, three patients), while seven of the 17 had fever and
      vancomycin-resistant Enterococcus in stool cultures. All patients were considered
      clinically cured after the end of the linezolid regimen (100% efficacy). The main
      adverse events were thrombocytopenia grade 1-3 and anemia grade 2-3 (four and two
      patients, respectively). Chemotherapy-induced myelotoxicity (six patients) was
      not worsened during linezolid therapy. No bleeding episodes were presented. Self
      limited diarrhea grade 1-2 was presented in four patients (mean duration 2 days).
      The total adverse event rate was 23.5%; however, there was no premature cessation
      of linezolid in any patient. CONCLUSIONS: Linezolid may be another effective and
      safe therapy to treat infections from resistant Gram-positive bacteria in
      immunocompromised children, even in young ages.

PMID- 20149127
TI  - Bifid epiglottis: syndromic constituent rather than isolated anomaly.
AB  - BACKGROUND: Bifid epiglottis is a congenital malformation defined as a midline
      cleft of the epiglottis, which can be presented as an isolated anomaly as well as
      a part of malformation complexes. Its common occurrence in Pallister-Hall
      syndrome (PHS) has recently been attracting special attention. In the embryo,
      epiglottis, hypothalamus, and digital buds develop synchronously. Some
      disturbances during this stage may account for the concurrence of bifid
      epiglottis, hypothalamic hamartoma, and polysyndactyly in PHS. The incidence of
      bifid epiglottis remains unknown. METHODS: We report here four children with
      bifid epiglottis out of 472 children who underwent laryngoscopy during the period
      from January 1995 to December 2004 in our hospital. RESULTS: All four children
      presented stridor of variable degrees. One had a partial cleft of the epiglottis
      associated with only tracheomalacia. The other three had a complete cleft of the
      epiglottis associated with complex malformations: one had accessory auricles with
      preauricular sinus, polycystic kidney disease with intrahepatic biliary
      dilatation, endocardial cushion defect, and postaxial polydactyly; another had
      hypothalamic hamartoma, Hirschsprung disease, and polydactyly, which warranted a
      diagnosis of PHS; the other had no other dysmorphic features. CONCLUSION: Bifid
      epiglottis can be presented as a syndromic constituent of congenital malformation
      syndromes rather than as an isolated anomaly. A high index of suspicion of bifid
      epiglottis should be raised in children with brachy-poly-syndactyly and clinical
      symptoms of upper airway obstruction.

PMID- 20149128
TI  - JcDof1, a Dof transcription factor gene, is associated with the light-mediated
      circadian clock in Jatropha curcas.
AB  - Jatropha curcas is an economically important plant in terms of its seed oil.
      However, the molecular mechanisms underlying this plant response to light signals
      are unknown. One group of DNA-binding with one finger (Dof) transcription factor
      genes exhibits circadian rhythms and plays a crucial role in the control of
      flowering time by photoperiod perception in plants. In the present study, a full
      length cDNA designated JcDof1, containing a conserved Dof-DNA-binding domain, was
      isolated from J. curcas seedlings by yeast one hybrid library. Subcellular
      localization assays and yeast one hybrid systems confirmed that JcDof1 was
      localized to the onion epidermal cell nucleus, and exhibited DNA-binding and
      transcriptional activation activities in yeast. The JcDof1 expression was
      characterized by a circadian-clock oscillation under long day, short day and
      continuous light conditions, whereas in the etiolated cotyledons under continuous
      dark conditions, JcDof1 expression remained at relatively basal levels. Red and
      blue light downregulated the JcDof1 expression, but this effect was not observed
      under far-red light. Taken together, these results suggested that JcDof1 was a
      circadian clock-Dof transcription factor gene responding to light signals.

PMID- 20149129
TI  - Analysis of fast chlorophyll fluorescence rise (O-K-J-I-P) curves in green fruits
      indicates electron flow limitations at the donor side of PSII and the acceptor
      sides of both photosystems.
AB  - Limited evidence up to now indicates low linear photosynthetic electron flow and
      CO(2) assimilation rates in non-foliar chloroplasts. In this investigation, we
      used chlorophyll fluorescence techniques to locate possible limiting steps in
      photosystem function in exposed, non-stressed green fruits (both pericarps and
      seeds) of three species, while corresponding leaves served as controls. Compared
      with leaves, fruit photosynthesis was characterized by less photon trapping and
      less quantum yields of electron flow, while the non-photochemical quenching was
      higher and potentially linked to enhanced carotenoid/chlorophyll ratios. Analysis
      of fast chlorophyll fluorescence rise curves revealed possible limitations both
      in the donor (oxygen evolving complex) and the acceptor (Q(A)(-)--> intermediate
      carriers) sides of photosystem II (PSII) indicating innately low PSII
      photochemical activity. On the other hand, PSI was characterized by faster
      reduction of its final electron acceptors and their small pool sizes. We argue
      that the fast reductive saturation of final PSI electron acceptors may divert
      electrons back to intermediate carriers facilitating a cyclic flow around PSI,
      while the partial inactivation of linear flow precludes strong reduction of
      plastoquinone. As such, the photosynthetic attributes of fruit chloroplasts may
      act to replenish the ATP lost because of hypoxia usually encountered in sink
      organs with high diffusive resistance to gas exchange.

PMID- 20149130
TI  - Lipoic acid and redox status in barley plants subjected to salinity and elevated
      CO2.
AB  - Future environmental conditions will include elevated concentrations of salt in
      the soil and an elevated concentration of CO(2) in the atmosphere. Because these
      environmental changes will likely affect reactive oxygen species (ROS) formation
      and cellular antioxidant metabolism in opposite ways, we analyzed changes in
      cellular H(2)O(2) and non-enzymatic antioxidant metabolite [lipoic acid (LA),
      ascorbate (ASA), glutathione (GSH)] content induced by salt stress (0, 80, 160 or
      240 mM NaCl) under ambient (350 micromol mol(-1)) or elevated (700 micromol mol(
      1)) CO(2) concentrations in two barley cultivars (Hordeum vulgare L.) that differ
      in sensitivity to salinity (cv. Alpha is more sensitive than cv. Iranis). Under
      non-salinized conditions, elevated CO(2) increased LA content, while ASA and GSH
      content decreased. Under salinized conditions and ambient CO(2), ASA increased,
      while GSH and LA decreased. At 240 mM NaCl, H(2)O(2) increased in Alpha and
      decreased in Iranis. When salt stress was imposed at elevated CO(2), less
      oxidative stress and lower increases in ASA were detected, while LA was
      constitutively higher. The decrease in oxidative stress could have been because
      of less ROS formation or to a higher constitutive LA level, which might have
      improved regulation of ASA and GSH reductions. Iranis had a greater capacity to
      synthesize ASA de novo and had higher constitutive LA content than did Alpha.
      Therefore, we conclude that elevated CO(2) protects barley cultivars against
      oxidative damage. However, the magnitude of the positive effect is cultivar
      specific.

PMID- 20149131
TI  - OsSPX1 suppresses the function of OsPHR2 in the regulation of expression of OsPT2
      and phosphate homeostasis in shoots of rice.
AB  - Phosphate (Pi) homeostasis in plants is required for plant growth and
      development, and is achieved by the coordination of Pi acquisition, translocation
      from roots to shoots, and remobilization within plants. Previous reports have
      demonstrated that over-expression of OsPHR2 (the homolog of AtPHR1) and knockdown
      of OsSPX1 result in accumulation of excessive shoot Pi in rice. Here we report
      that OsPHR2 positively regulates the low-affinity Pi transporter gene OsPT2 by
      physical interaction and upstream regulation of OsPHO2 in roots. OsPT2 is
      responsible for most of the OsPHR2-mediated accumulation of excess shoot Pi.
      OsSPX1 suppresses the regulation on expression of OsPT2 by OsPHR2 and the
      accumulation of excess shoot Pi, but it does not suppress induction of OsPT2 or
      the accumulation of excessive shoot Pi in the Ospho2 mutant. Our data also show
      that OsSPX1 is a negative regulator of OsPHR2 and is involved in the feedback of
      Pi-signaling network in roots that is defined by OsPHR2 and OsPHO2. This finding
      provides new insight into the regulatory mechanism of Pi uptake, translocation,
      allocation and homeostasis in plants.

PMID- 20149132
TI  - The Arabidopsis defense component EDM2 affects the floral transition in an FLC
      dependent manner.
AB  - Arabidopsis thaliana EDM2 was previously shown to be specifically required for
      disease resistance mediated by the R protein RPP7. Here we provide additional
      data showing that the role of EDM2 in plant immunity is limited and does not
      include a function in basal defense. In addition, we found that EDM2 has a
      promoting effect on the floral transition. We further found that the protein
      kinase WNK8 physically interacts with EDM2 in the nucleus. Unlike EDM2, which
      serves as a substrate of this kinase, WNK8 appears not to be required for RPP7
      mediated defense. As reported previously, however, WNK8 does affect flowering
      time. Epistasis analyses suggested that EDM2 acts upstream of the floral
      repressor FLC (AT5G10140) and downstream of WNK8 (AT5G41990) in a regulatory
      module that resembles the autonomous floral promotion pathway, comprising a set
      of mechanisms that are known to affect the floral transition by regulating FLC
      transcript levels.

PMID- 20149133
TI  - Mutual regulation of plant phospholipase D and the actin cytoskeleton.
AB  - Membrane lipids and cytoskeleton dynamics are intimately inter-connected in the
      eukaryotic cell; however, only recently have the molecular mechanisms operating
      at this interface in plant cells been addressed experimentally. Phospholipase D
      (PLD) and its product phosphatidic acid (PA) were discovered to be important
      regulators in the membrane-cytoskeleton interface in eukaryotes. Here we report
      the mechanistic details of plant PLD-actin interactions. Inhibition of PLD by n
      butanol compromises pollen tube actin, and PA rescues the detrimental effect of n
      butanol on F-actin, showing clearly the importance of the PLD-PA interaction for
      pollen tube F-actin dynamics. From various candidate tobacco PLDs isoforms, we
      identified NtPLDbeta1 as a regulatory partner of actin, by both activity and in
      vitro interaction assays. Similarly to published data, the activity of tobacco
      PIP(2)-dependent PLD (PLDbeta) is specifically enhanced by F-actin and inhibited
      by G-actin. We then identified the NtPLDbeta1 domain responsible for actin
      interactions. Using sequence- and structure-based analysis, together with site
      directed mutagenesis, we identified Asn323 and Thr382 of NtPLDbeta1 as the
      crucial amino acids in the actin-interacting fold. The effect of antisense
      mediated suppression of NtPLDbeta1 or NtPLDdelta on pollen tube F-actin dynamics
      shows that NtPLDbeta1 is the active partner in PLD-actin interplay. The positive
      feedback loop created by activation of PLDbeta by F-actin and of F-actin by PA
      provides an important mechanism to locally increase membrane-F-actin dynamics in
      the cortex of plant cells.

PMID- 20149135
TI  - Mutation spectrum of the first melanoma genome points finger firmly at
      ultraviolet light as the primary carcinogen.

PMID- 20149136
TI  - PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and
      enhances cell migration and proliferation of BRAF melanoma cells.
AB  - BRAF(V600E/K) is a frequent mutationally active tumor-specific kinase in
      melanomas that is currently targeted for therapy by the specific inhibitor
      PLX4032. Our studies with melanoma tumor cells that are BRAF(V600E/K) and
      BRAF(WT) showed that, paradoxically, while PLX4032 inhibited ERK1/2 in the highly
      sensitive BRAF(V600E/K), it activated the pathway in the resistant BRAF(WT)
      cells, via RAF1 activation, regardless of the status of mutations in NRAS or
      PTEN. The persistently active ERK1/2 triggered downstream effectors in BRAF(WT)
      melanoma cells and induced changes in the expression of a wide-spectrum of genes
      associated with cell cycle control. Furthermore, PLX4032 increased the rate of
      proliferation of growth factor-dependent NRAS Q61L mutant primary melanoma cells,
      reduced cell adherence and increased mobility of cells from advanced lesions. The
      results suggest that the drug can confer an advantage to BRAF(WT) primary and
      metastatic tumor cells in vivo and provide markers for monitoring clinical
      responses.

PMID- 20149137
TI  - Isolating the internal in endogenous attention.
AB  - Neuroimaging studies have provided evidence that a bilateral frontal-parietal
      network is involved in voluntary attentional control. However, because those
      studies used instructive cue stimuli, some of the activity may have been due to
      interactions between cue processing and voluntary orienting. Here, we show that
      self-initiated voluntary orienting, in the absence of any cue stimulus, evokes
      activity in this frontal-parietal network. In contrast to the typical symmetric
      activity observed with cued attentional shifts, self-initiated shifts showed a
      hemispheric asymmetry consistent with studies of unilateral neglect patients.
      Specifically, the right hemisphere was equally involved in orienting to either
      visual field, whereas the left hemisphere was biased toward the contralateral
      field. Our data show that the asymmetry of attentional control can be revealed in
      neuroimaging of healthy subjects, when voluntary orienting is effectively
      isolated.

PMID- 20149138
TI  - Nitric oxide and superoxide anion production during heparin-induced capacitation
      in cryopreserved bovine spermatozoa.
AB  - The aim of this work was to quantify NO,O(2)(-) and ONOO(-) production during
      heparin-induced capacitation of cryopreserved bovine spermatozoa. A time
      dependent hyperbolic increase was observed for heparin-dependent capacitation,
      O(2) uptake, and NO production. Conversely, O(2)(-) production was increased
      during the first 15 min of incubation, showing a decrease from this time until 45
      min. At 15 min of heparin incubation, a threefold increase in O(2) consumption
      (5.9 +/- 0.6 nmol/min * 10(7) cells), an enhancement in NO release (1.1 +/- 0.2
      nmol/min * 10(7) cells), and a five-fold increase in O(2)(-) production (1.3 +/-
      0.07 nmol/min * 10(7) cells), were observed. Peroxynitrite production rate was
      estimated taking into account NO and O(2)(-) generation and the second-order rate
      constant of the reaction between these species. To conclude, heparin-induced
      capacitation of cryopreserved bovine spermatozoa activates (i) mitochondrial O(2)
      uptake by high ADP levels due to increased energy requirements, (ii) NO
      production by a constitutive NOS and (iii) O(2)(-) production by a membrane-bound
      NAD(P)H oxidase. The products of both enzymes are released to the extracellular
      space and could be involved in the process of sperm capacitation.

PMID- 20149139
TI  - Proliferation and apoptosis in aged and photoregressed mammalian seminiferous
      epithelium, with particular attention to rodents and humans.
AB  - Imbalances in the proliferation and apoptosis processes are involved in numerous
      epithelial alterations. In the seminiferous epithelium, normal spermatogenesis is
      regulated by spermatogonia proliferation and germ cell apoptosis, and both
      processes are involved in diverse pathological alterations of the seminiferous
      epithelium. Other physiological phenomena including aging and short photoperiod,
      in which apoptosis and proliferation seem to play important roles, cause
      testicular changes. Aging is accompanied by diminished proliferation and
      increased apoptosis, the latter occurring in specific states of the seminiferous
      cycle and considered the cause of epithelium involution. However, there is no
      clear evidence concerning whether proliferation decreases in the spermatogonia
      themselves or is due to an alteration in the cell microenvironment that surrounds
      them. As regards the factors that regulate the process, the data are scant, but
      it is considered that the diminution of c-kit expression in the spermatagonia,
      together with the diminution in antiapoptotic factors (Bcl-x(L))) of the
      intrinsic molecular pathway of apoptosis play a part in epithelial regression. A
      short photoperiod, especially in rodents, produces a gradual involution of the
      seminiferous epithelium, which is related with increased apoptosis during the
      regression phase and a diminution of apoptosis during recrudescence.
      Proliferative activity varies, especially during the total regression phase, when
      it usually increases in the undifferentiated spermatogonia. In other species
      showing seasonal reproduction, however, decreased proliferation is considered the
      main factor in the regression of the seminiferous epithelium. Little is known
      about how both phenomena are regulated, although data in rodents suggest that
      both the intrinsic and extrinsic pathways of apoptosis contribute to the increase
      in this process. In conclusion, regression of the seminiferous epithelium in
      physiological situations, as in many pathological situations, is a result of
      alterations in equilibrium between the proliferation and apoptosis of germinal
      cell types. However, both physiological phenomena showed important differences as
      regard proliferation/apoptosis and their regulation pathways, probably as a
      result of their irreversible or reversible character.

PMID- 20149140
TI  - Evidence that refractoriness to long and short daylengths regulates seasonal
      reproductive transitions in Mediterranean goats.
AB  - Two experiments were performed to assess the role of refractoriness to long and
      short daylengths in the timing of seasonal reproductive transitions in
      Mediterranean Malaguena goats. In the first experiment, intact adult does were
      either maintained under natural photoperiod conditions (NP; n = 5) or exposed to
      a constant long day photoperiod (LD - 16 h light/day; n = 5) from June to
      December 2005. In the second experiment, does were maintained either under NP
      conditions (n = 5) or received a series of subcutaneous melatonin implants (MI)
      from December 2005 to June 2006 to mimic a short day signal (n = 5). In both
      experiments, ovulatory activity was assayed by determining progesterone
      concentrations in blood samples collected twice per week. The onset of seasonal
      ovulatory activity did not differ (p > 0.05) between the LD and NP does (3
      October +/-5 days and 23 September +/-3 days respectively). The simulated short
      days did not modify (p > 0.05) the timing of the end of ovulatory activity. The
      MI does become anoestrus at the same time (1 March +/-9 days) as their NP
      counterparts (23 February +/-8 days). These results indicate that, in Malaguena
      does, the onset and offset of anoestrus are not driven by photoperiod changes but
      appear to be the result of long and short day refractoriness respectively. An
      endogenous circannual rhythm may therefore be involved in regulating seasonal
      reproductive changes in these animals.

PMID- 20149141
TI  - Sorting of plant vacuolar proteins is initiated in the ER.
AB  - Transport of soluble cargo molecules to the lytic vacuole of plants requires
      vacuolar sorting receptors (VSRs) to divert transport of vacuolar cargo from the
      default secretory route to the cell surface. Just as important is the trafficking
      of the VSRs themselves, a process that encompasses anterograde transport of
      receptor-ligand complexes from a donor compartment, dissociation of these
      complexes upon arrival at the target compartment, and recycling of the receptor
      back to the donor compartment for a further round of ligand transport. We have
      previously shown that retromer-mediated recycling of the plant VSR BP80 starts at
      the trans-Golgi network (TGN). Here we demonstrate that inhibition of retromer
      function by either RNAi knockdown of sorting nexins (SNXs) or co-expression of
      mutants of SNX1/2a specifically inhibits the ER export of VSRs as well as soluble
      vacuolar cargo molecules, but does not influence cargo molecules destined for the
      COPII-mediated transport route. Retention of soluble cargo despite ongoing COPII
      mediated bulk flow can only be explained by an interaction with membrane-bound
      proteins. Therefore, we examined whether VSRs are capable of binding their
      ligands in the lumen of the ER by expressing ER-anchored VSR derivatives. These
      experiments resulted in drastic accumulation of soluble vacuolar cargo molecules
      in the ER. This demonstrates that the ER, rather than the TGN, is the location of
      the initial VSR-ligand interaction. It also implies that the retromer-mediated
      recycling route for the VSRs leads from the TGN back to the ER.

PMID- 20149142
TI  - Changes of connexin43 expression in non-pregnant porcine myometrium correlate
      with progesterone concentration during oestrous cycle.
AB  - Connexin43 (Cx43) is a major protein of myometrial gap junctions. The number of
      Cx43 gap junctions increase dramatically with the onset of labour in association
      with development of synchronized uterine contractions. The formation of
      myometrial gap junctions follows an increase in the oestrogen to progesterone
      ratio indicating an important role of steroid hormones in regulating Cx43
      expression at term. However, no relationship has been established between the
      expression of Cx43 in the non-pregnant myometrium and concentration of steroid
      hormones during the oestrous cycle. Here, we used immunofluorescence and Western
      blotting to analyse the expression of Cx43 gap junctions in the myometrium of pre
      pubertal pigs (n = 7) and mature pigs at pre-ovulatory (n = 7), luteal (n = 5)
      and late luteal (n = 3) stages of the oestrous cycle. The number of Cx43 gap
      junctions calculated per 1 mm(2) of the myometrial section was low in pre
      pubertal pigs and significantly higher (p < 0.022) in pre-ovulatory animals. In
      relation to pre-ovulatory animals the number of myometrial gap junctions was
      significantly lower (p < 0.019) at the luteal phase and correlated with
      significantly higher (p < 0.005) concentration of endogenous progesterone.
      Phosphorylated isoforms of Cx43 protein were expressed in the myometrium of pre
      pubertal pigs and mature animals at pre-ovulatory and late luteal phases, while
      they were down regulated at the luteal stage. These results indicate that changes
      of Cx43 expression in the porcine myometrium during the oestrous cycle may be
      regulated by progesterone concentration and may contribute to the modulation of
      uterine motility.

PMID- 20149143
TI  - Activity profile and physiological response to football training for untrained
      males and females, elderly and youngsters: influence of the number of players.
AB  - The present study examined the activity profile, heart rate and metabolic
      response of small-sided football games for untrained males (UM, n=26) and females
      (UF, n=21) and investigated the influence of the number of players (UM: 1v1, 3v3,
      7v7; UF: 2v2, 4v4 and 7v7). Moreover, heart rate response to small-sided games
      was studied for children aged 9 and 12 years (C9+C12, n=75), as well as homeless
      (HM, n=15), middle-aged (MM, n=9) and elderly (EM, n=11) men. During 7v7, muscle
      glycogen decreased more for UM than UF (28 +/- 6 vs 11 +/- 5%; P<0.05) and
      lactate increased more (18.4 +/- 3.6 vs 10.8 +/- 2.1 mmol kg(-1) d.w.; P<0.05).
      For UM, glycogen decreased in all fiber types and blood lactate, glucose and
      plasma FFA was elevated (P<0.05). The mean heart rate (HR(mean)) and time >90% of
      HR(max) ranged from 147 +/- 4 (EM) to 162 +/- 2 (UM) b.p.m. and 10.8 +/- 1.5 (UF)
      to 47.8 +/- 5.8% (EM). Time >90% of HR(max) (UM: 16-17%; UF: 8-13%) and time
      spent with high speed running (4.1-5.1%) was similar for training with 2-14
      players, but more high-intensity runs were performed with few players (UM 1v1:
      140 +/- 17; UM 7v7: 97 +/- 5; P<0.05): Small-sided games were shown to elucidate
      high heart rates for all player groups, independently of age, sex, social
      background and number of players, and a high number of intense actions both for
      men and women. Thus, small-sided football games appear to have the potential to
      create physiological adaptations and improve performance with regular training
      for a variety of study groups.

PMID- 20149144
TI  - Adolescent stress: evaluation of the factor structure of the Adolescent Stress
      Questionnaire (ASQ-N).
AB  - The present study reports an evaluation of the factor structure of the Norwegian
      version of the Adolescent Stress Questionnaire (ASQ-N) among 723 students.
      Principal components analysis (PCA) revealed nine internally consistent
      dimensions of adolescent stress. Scales constructed from this PCA correlated
      positively with measures of depression and anxiety and negatively with self
      esteem. Girls reported higher stress levels than boys in seven of the nine scales
      and age was also positively correlated with the scale scores of adolescent
      stress. The results revealed that the instrument has potential for measuring
      adolescent stress. The stability of the ASQ-N needs to be tested repeatedly,
      across cohorts and over time, to establish the adequacy for use in Norwegian
      adolescent studies.

PMID- 20149145
TI  - A randomized study of the impact of a sensitizing intervention on the child
      rearing attitudes of parents of low birth weight preterm infants.
AB  - The background for this study was that nurturant child-rearing attitudes are
      associated with positive development in low birth weight (LBW) infants. The
      objective was to study child-rearing attitudes and early intervention (EI) in
      parents of LBW infants from 12-36 months corrected age. LBW infants (BW< 2000 g)
      were randomized to an intervention (IG) or a control group (CG). The EI consisted
      of seven in-hospital sessions prior to discharge, then four home visits. A Child
      Rearing Practices Report was administered at 12 (mothers only), 24 and 36 months.
      A total of 146 infants were randomized. The mean BW in IG was 1396 (SD 429) g and
      1381 (436) g in CG. The mean GA was 30.2 (3.1) weeks in IG and 29.9 (3.5) weeks
      in CG. Mothers in IG reported significantly more nurturant child-rearing
      attitudes at 12 and 24 months. There was a significant change in restrictive and
      nurturant attitudes over time. It was concluded that EI may lead to more
      nurturant child-rearing attitudes in mothers of preterms.

PMID- 20149146
TI  - Cross-cultural validation of the Resilience Scale for Adults (RSA) in Iran.
AB  - Resilience, as an ability to withstand and rebound from crisis and adversity, is
      becoming an increasingly popular concept in research on intervention and
      prevention of mental health. The present study examined psychometric properties
      of a Persian version of the Resilience Scale for Adults (RSA), a scale intended
      to measure protective factors presumed to enhance resilience. The participants
      were 373 university undergraduate students, as well as 30 pairs of run-away girls
      and a matched control group. A confirmatory factor analysis verified the
      Norwegian five-factor structure. All subscale scores, personal competence, social
      competence, family cohesion, social resources and structured style, had good
      reliability. The convergent validity of the RSA was supported by showing positive
      associations with another resilience scale, i.e., a Persian version of the Connor
      Davidson Resilience Scale (CD-RISC). Predictive validity of the RSA was
      supported, as well, by significantly differentiating between girls who had run
      away from home and a matched control group. The results indicate that the RSA may
      be a valid and reliable scale for the assessment of resilience protective
      resources in an Iranian population.

PMID- 20149147
TI  - Aesthetic anti-ageing surgery and technology: women's friend or foe?
AB  - This study investigates women's attitudes about, and experiences of, aesthetic
      anti-ageing surgeries and technologies against the contextual backdrop of the
      growing commercialisation of medicine in the United States. Drawing from 44
      intensive interviews with a spectrum of women between the ages of 47 and 76 who
      use, refuse, and are currently undecided about whether or not they will have or
      use aesthetic anti-ageing surgeries and technologies in the future, this study
      asks the following question: in what ways does the increasing availability,
      accessibility, advertising, and use of aesthetic anti-ageing surgeries and
      technologies interact with and inform women's perceptions and attitudes about
      growing older? Data analysis occurs in dialogue with the paradigms of successful
      ageing and agelessness and draws from, and contributes new readings of,
      contemporary cultural constructions of femininity.

PMID- 20149148
TI  - Observing the work of an urban safety-net psychiatric emergency room: managing
      the unmanageable.
AB  - Staff in the psychiatric emergency room (PER) have demanding jobs requiring a
      complex balance between the needs and safety of the individual and the community,
      systemic resources, and job responsibilities while providing timely, effective
      care. Little research exists concerning day-to-day work activities of PER staff,
      their interaction, and their perceptions of their work. This study explored the
      work of PER staff and the organisational context of the PER work setting.
      Observations of staff were conducted in the public spaces of a public urban PER
      using two observational techniques. The first was designed to measure the types
      of work activities staff engaged in and the time spent in these work activities
      (work task data). The second technique was the gathering of observational data by
      a peripheral-member-researcher (participant observation data). Analyses were
      conducted of both the work task and participant observation data. Results
      indicate that most PER staff time is spent in administrative and phone tasks,
      while less than a third is spent on direct clinical work. Four important issues
      for PER work were identified: a workload that is unmanageable, managing the
      unmanageable, bogus referrals and dumping and insurance problems. The PER remains
      the front-line of the medical and social service systems. Work done in these
      settings is of critical importance; however little attention is paid to the
      content and nature of the work. Our study demonstrates that staff of the PER face
      challenges on many levels as they struggle with the task of working with people
      presenting in psychiatric and social crisis.

PMID- 20149149
TI  - Morgellons: contested illness, diagnostic compromise and medicalisation.
AB  - The case of Morgellons illustrates how the emergence of a new medically contested
      illness intersected with and impacted on the diagnostic processes of an existing
      uncontested psychiatric condition, Delusional Parasitosis (DP). More
      specifically, the sociopolitical processes at play in the contested illness,
      Morgellons, dubiously reflect patient empowerment, as well the resilience and
      power of medical jurisdiction. This research offers insights into the contested
      illness and medicalisation literatures, and aims to bridge these two approaches
      towards the relationship between patient empowerment and medical authority, which
      I do through the notion of doctor-patient compromise. The data for this research
      come from a comprehensive qualitative analysis of Morgellons discourse through
      four key sources: the pro-Morgellons website Morgellons.org; the anti-Morgellons
      website Morgellonswatch.com; the popular media's portrayal of Morgellons; and the
      DP and Morgellons articles published in peer-reviewed medical journals, as made
      available on PubMed.

PMID- 20149150
TI  - Doing it my way: old women, technology and wellbeing.
AB  - This article focuses on women in their nineties (nonagenarians) who are ageing in
      place - or ageing at home - in upstate New York. I analyse these old women's use
      of everyday technological tools to care for themselves and construct meaning. I
      argue that despite what we may expect, nonagenarian women can be and are
      technogenarians in their active and creative uses of everyday technologies. Old
      women utilise lifelong care work repertoires to identify, adjust, use and reject
      old and new technologies for their own everyday mobility, communication,
      nourishment, and physiological health. Perhaps most importantly techno-savvy
      elders can maintain and achieve health and wellbeing, associated here with bodily
      comfort, social networks, self-efficacy and intellectual life, in and beyond
      their homes. In these ways, nonagenarians can teach us how household technologies
      can be health and ageing technologies; instruments of continuity and control; or
      just the opposite.

PMID- 20149151
TI  - 'But obviously not for me': robots, laboratories and the defiant identity of
      elder test users.
AB  - This article focuses on participants and researchers who actively tested a
      prototype - a robot intended to enhance the health of elders. Specifically, this
      article analyses interactions between robots, elder test users, and robot
      designers to examine how images of elder users, definitions of health, and ideas
      about ageing shape the development of technology. The designers imagined the
      prospective user as a person who would both need and want a health robot. In
      contrast, test users drew upon stereotypes of old people and imagined the
      prospective user as a lonely person in need of care and company. To resist this
      stereotype, they presented themselves as cognitively and physically healthy,
      independent, and helpful. This image of the helpful test user allowed
      participants to simultaneously enjoy the robot and position themselves as not old
      or in need of care. The participants' views, however, did not influence the
      designers' overall view of elder users, and were not incorporated into their
      design practices. Recognising and taking into account test users' views on elder
      technology users - specifically their understanding and rejection of negative
      stereotypes of old people - could help prevent resistance to (and thus the non
      use of) health technologies by elders.

PMID- 20149152
TI  - A history of the future: the emergence of contemporary anti-ageing medicine.
AB  - The emergence of anti-ageing medicine over the past 20 years has posed tremendous
      challenges for the understanding of ageing and the concomitant responsibilities
      of biomedicine. Though highly contentious and loosely organised at best, anti
      ageing targets ageing for biomedical intervention. This article examines a
      history of anti-ageing in the United States from 1993 to 2008, outlining its
      evolution from a scientific 'backwater' to a field with such promise that many
      within and outside the field believe efficacious therapies are an inevitability.
      In large part, the language of anti-ageing has shifted from predictions to
      expectations; it has become less a question of 'if' and more a question of 'when'
      and 'how' this rhetorical shift is directly linked with increasing legitimacy
      constructed upon a complex web of factors including mounting practitioner
      involvement, research interest, media attention, and popular desire. In this
      article I briefly review this history alongside the strategic histories
      marshalled by the various proponents and opponents to support their claims of
      legitimacy. The history of anti-ageing medicine is one of an emerging scientific
      and clinical practice as well as a history of an idea that has very recently made
      its way out of science fiction and into science future.

PMID- 20149153
TI  - 'A second youth': pursuing happiness and respectability through cosmetic surgery
      in Finland.
AB  - The paper discusses cosmetic surgery in the Finnish cultural context. It is based
      on interviews with 22 women and men who underwent surgical procedures, 12 plastic
      surgeons, and two plastic surgery consultants. The article shows that surgery
      consumers over 55 years old discuss cosmetic surgery as an investment in a better
      quality of life. Consumers use cosmetic surgery to resist ageist stereotypes of
      old people and as compensation for tough life experiences which are believed to
      cause premature ageing. Although aimed at combatting negative attitudes towards
      old people, such efforts reproduce an ageist ideology by concealing the very
      qualities (e.g. wrinkles) associated with ageing. Finally, consumers use cosmetic
      surgery to correct perceived Finnish physical pathologies, such as heavy
      foreheads, sagging eyelids, and 'potato' noses, which make them seem less white,
      sadder, and older than they are. The traditional melancholic Finnish body is thus
      transformed via surgery to represent openness and positiveness - two qualities
      strongly associated with both youth and the Americanised ideal as it is touted in
      Finland. The article demonstrates that consumers use cosmetic surgery to
      transform both physical and emotional states and that cosmetic surgery must be
      understood as part of national and global cultural processes.

PMID- 20149154
TI  - Science, medicine and virility surveillance: 'sexy seniors' in the pharmaceutical
      imagination.
AB  - Abstract While historically sex has been seen primarily as the prerogative of the
      young, more recently, the emphasis has been on the maintenance of active
      sexuality as a marker of successful ageing. A new cultural consensus appears to
      have emerged which not only emphasises the importance of continued sexual
      activity across the lifespan, but links sexual function with overall health and
      encourages increased self-surveillance of, and medical attention to, late-life
      sexuality. Drawing on historical accounts, clinical research, popular science
      reporting and health promotion literatures, I explore several key shifts in
      models of sexual ageing, culminating in the contemporary model of gender,
      sexuality and ageing that has made ageing populations a key market for
      biotechnologies aimed at enhancing sexual function. Two central concepts frame my
      analysis: 'virility surveillance', where age-related changes in sexual function
      are taken as indicative of decline, and the 'pharmaceutical imagination', where
      sexual lifecourses are reconstructed as drug effects revise standards of sexual
      function. After consideration of how narratives emerging from qualitative
      research with older adults challenge the narrow depiction of sexual functionality
      promoted by pharmaculture, conclusions call for continued critical inquiry into
      the biomedical construction of sex and age.

PMID- 20149155
TI  - Distinct roles of myosin Va in membrane remodeling and exocytosis of secretory
      granules.
AB  - Hormone- and neuropeptide-containing secretory granules (SGs) of neuroendocrine
      PC12 cells are formed at the trans- Golgi network as immature SGs. These
      intermediates are converted to mature SGs in a complex maturation process,
      including matrix condensation, processing of cargo proteins and removal of
      proteins and membrane in clathrin-coated vesicles. The resulting mature SGs
      undergo Ca2+-dependent exocytosis upon an appropriate stimulus. We here show that
      the motor protein myosin Va is implicated in a maturation step of SGs, their
      binding to F-actin and their stimulated exocytosis. Interference with myosin Va
      function blocked the removal of the transmembrane protein furin from maturing SGs
      without affecting condensation and processing of proteins of the SG lumen.
      Furthermore, the ATP-inhibited binding of SGs to F-actin decreased with
      progressive maturation and upon interference with myosin Va function. Moreover,
      the expression of a dominant-negative myosin Va-tail or shRNA-based
      downregulation of myosin Va interfered with stimulated exocytosis of SGs. In
      summary,our data suggest an essential function of myosin Va in the membrane
      remodeling of SGs during maturation and a role in their exocytosis.

PMID- 20149157
TI  - Arboviruses in blood donors: a study in the Amazon region and in a small city
      with a dengue outbreak.

PMID- 20149156
TI  - A probable case of transfusion-transmitted hepatitis B virus infection in an
      immunosuppressed recipient caused by an occult HBV-infected donor with negative
      ID-NAT.

PMID- 20149158
TI  - Impaired metabolism in donor kidney grafts after steroid pretreatment.
AB  - Summary We recently showed in a randomized control trial that steroid
      pretreatment of the deceased organ donor suppressed inflammation in the
      transplant organ but did not reduce the rate or duration of delayed graft
      function (DGF). This study sought to elucidate such of those factors that caused
      DGF in the steroid-treated subjects. Genome-wide gene expression profiles were
      used from 20 steroid-pretreated donor-organs and were analyzed on the level of
      regulatory protein-protein interaction networks. Significance analysis of
      microarrays (SAM) yielded 63 significantly down-regulated sequences associated
      with DGF that could be functionally categorized according to Protein ANalysis
      THrough Evolutionary Relationships ontologies into two main biologic processes:
      transport (P < 0.001) and metabolism (P < 0.001). The identified genes suggest
      hypoxia as the cause of DGF, which cannot be counterbalanced by steroid
      treatment. Our data showed that molecular pathways affected by ischemia such as
      transport and metabolism are associated with DGF. Potential interventional
      targeted therapy based on these findings includes peroxisome proliferator
      activated receptor agonists or caspase inhibitors.

PMID- 20149159
TI  - High plasma hemopexin activity is an independent risk factor for late graft
      failure in renal transplant recipients.
AB  - Chronic low-grade inflammation is involved in late renal transplant dysfunction.
      Recent studies suggest a role for hemopexin, an acute phase protein, in kidney
      damage. We investigated whether hemopexin activity (Hx) predicts graft failure in
      renal transplant recipients (RTRs). In 557 RTRs with functioning grafts for >or=1
      year, Hx was measured in citrate-plasma. RTRs were divided according to Hx into
      two groups; A: sextile 1-5 (464 RTRs, 83%) and B: sextile 6 (92 RTRs, 17%). Hx
      [median (IQR) 11.1 (3.3-19.1) arbitrary units] was measured at 6.0 (2.6-11.5)
      years post-transplant. RTRs with high Hx (group B) had significantly higher
      urinary protein excretion (UP) and diastolic blood pressure than group A, despite
      significantly more prevalent use of renin-angiotensin-aldosterone system
      inhibitors. After follow-up [4.6 (3.8-5.2) years], incidence of graft failure in
      group A was 25 (5%) and in group B 14 (15%,P = 0.0009) After adjustment for high
      sensitivity C-reactive protein (hsCRP), UP and other potential confounders, Hx
      remained an independent predictor of graft failure [HR = 2.5 (95% CI 1.2-5.3), P
      = 0.01]. In conclusion, elevated Hx predicts late graft failure in RTRs,
      independent of hsCRP and UP. This suggests that Hx measurement, next to
      measurement of creatinine clearance and UP, could be of value for the
      identification of RTRs at risk for graft failure.

PMID- 20149160
TI  - Human platelet antigen allele frequencies in different Algerian populations.
AB  - The frequencies of human platelet antigens (HPAs) vary between different
      populations and are a major determinant for the prevalence of HPA
      alloimmunization and its clinically associated entities. No report on HPA
      prevalence has previously been published for the Algerian populations which are
      ethnically diverse. The aim of this study was to determine the HPA allele
      frequencies in Algerian populations and to identify situations of incompatibility
      possibly leading to alloimmunization. A total of 485 healthy volunteer Algerian
      blood donors from different regions and representing different ethnic groups were
      included. HPA genotyping was determined by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) and/or polymerase chain reaction-sequence
      specific primer (PCR-SSP). The HPA-1 allele frequencies were close to the
      frequencies found in Caucasian populations. The presence of the molecule human
      leukocyte antigen (HLA)-DRB3*0101 (17.9%) increases the risk of alloimmunization.
      We observed an increase in the frequency of homozygous HPA-5b, particularly in
      the population of Annaba (7.61%) and the Mzab population (5.13%). The allele
      frequency HPA-2b (0.193-0.147) was similar to that seen in Sub-Saharan African
      populations. The high frequency of homozygotic HPA-2b (Kabyle 5%; Mzab 2.44% and
      Annaba 2.19%) could increase the risk of alloimmunization. GPIIb A(k) mutation
      (2614C>A) was found in these populations. This study is the first to report on
      HPA allele frequencies in Algerian populations. High allele frequencies were
      observed for HPA-1b (0.209-0.112), HPA-3b (0.411-0.312) and HPA-5b (0.217-0.087),
      leading to a high risk of alloimmunization in this population, especially the
      Mzab and the population of Annaba. Our results could have some impact in the
      diagnosis, prevention and treatment of alloimmune thrombocytopenia.

PMID- 20149161
TI  - Identification of a novel HLA class I allele, HLA-Cw*0134 in a Chinese
      individual.
AB  - The new human leukocyte antigen (HLA) class I allele, HLA-Cw*0134, was identified
      in a Chinese individual. HLA-Cw*0134 differs from HLA-Cw*0124 by one
      nonsynonymous nucleotide change at the codon 99 (TGT to TAT) and one synonymous
      nucleotide change at the codon 127 (AAC to AAT).

PMID- 20149163
TI  - Long-lasting insecticide-treated net usage in eastern Sierra Leone - the success
      of free distribution.
AB  - OBJECTIVE: Medecins Sans Frontieres (MSF) runs a malaria control project in Bo
      and Pujehun districts (population 158 000) that includes the mass distribution,
      routine delivery and demonstration of correct use of free, long-lasting
      insecticide-treated nets (LLINs). In 2006/2007, around 65 000 LLINs were
      distributed. The aim of this follow-up study was to measure LLIN usage and
      ownership in the project area. METHODS: Heads of 900 randomly selected households
      in 30 clusters were interviewed, using a standardized questionnaire, about
      household use of LLINs. The condition of any LLIN was physically assessed.
      RESULTS: Of the 900 households reported, 83.4% owning at least one LLIN. Of the
      16.6% without an LLIN, 91.9% had not participated in the MSF mass distribution.
      In 94.1% of the households reporting LLINs, the nets were observed hanging
      correctly over the beds. Of the 1135 hanging LLINs, 75.2% had no holes or 10 or
      fewer finger-size holes. The most common source of LLINs was MSF (75.2%). Of the
      4997 household members, 67.2% reported sleeping under an LLIN the night before
      the study, including 76.8% of children under 5 years and 73.0% of pregnant women.
      CONCLUSION: Our results show that MSF achieved good usage with freely distributed
      LLINs. It is one of the few areas where results almost achieve the new targets
      set in 2005 by Roll Back Malaria to have at least 80% of pregnant women and
      children under 5 years using LLINs by 2010.

PMID- 20149162
TI  - A new allele, HLA-G*010120, is generated by a recombination event between HLA
      G*01010101/02 and HLA-G*01010201.
AB  - Recombination between HLA-G*01010101/02 and HLA-G*01010201 generates HLA
      G*010120.

PMID- 20149164
TI  - Primary Health Care in the 21st century: primary care providers and people's
      empowerment.

PMID- 20149165
TI  - A population-based study of how children are exposed to saliva in KwaZulu-Natal
      Province, South Africa: implications for the spread of saliva-borne pathogens to
      children.
AB  - OBJECTIVES: In sub-Saharan Africa, many viral infections, including Epstein-Barr
      virus, cytomegalovirus, Kaposi's sarcoma-associated herpesvirus and hepatitis B
      are acquired in childhood. While saliva is an important transmission conduit for
      these viruses, little is known about how saliva is passed to African children. We
      endeavoured to identify the range and determinants of acts by which African
      children are exposed to saliva. METHODS: To identify the range of acts by which
      African children are exposed to saliva, we conducted focus groups, semi
      structured interviews and participant observations in an urban and a rural
      community in South Africa. To measure the prevalence and determinants of the
      identified acts, we administered a questionnaire to a population-based sample of
      caregivers. RESULTS: We identified 12 caregiving practices that expose a child's
      oral-respiratory mucosa, cutaneous surfaces or anal-rectal mucosa to saliva.
      Several acts were heretofore not described in the contemporary literature (e.g.,
      caregiver inserting finger lubricated with saliva into child's rectum to relieve
      constipation). Among 896 participants in the population-based survey, many of the
      acts were commonly practised by all respondent types (mothers, fathers,
      grandmothers and siblings). The most common were premastication of food, sharing
      sweets and premastication of medicinal plants that are spit onto a child's body.
      CONCLUSIONS: African children are exposed to saliva through a variety of acts,
      practised by a variety of caregivers, with no single predominant practice. This
      diversity poses challenges for epidemiologic work seeking to identify specific
      saliva-passing practices that transmit viruses. Most acts could be replaced by
      other actions and are theoretically preventable.

PMID- 20149168
TI  - Effect of acepromazine or xylazine on tear production as measured by Schirmer
      tear test in normal cats.
AB  - OBJECTIVE: To evaluate the effect of acepromazine or xylazine on Schirmer tear
      test 1 results in clinically normal cats. ANIMALS: Sixteen healthy cross-breed
      cats. PROCEDURE: The animals were randomly divided into two groups of eight cats
      each. The first group was sedated with acepromazine alone (0.2 mg/kg) and the
      second group received only xylazine (2 mg/kg). All cats had Schirmer tear test
      (STT) readings taken prior to sedation and at 15 and 25 min postsedation.
      RESULTS: Sedation with acepromazine or xylazine in cats with normal pre-sedation
      STT 1 values caused a statistically significant decrease in mean values of tear
      production in both groups. In acepromazine group the mean +/- SEM STT at T(15)
      and T(25) were 4.31 +/- 0.98 (P < 0.001) and 5.18 +/- 1.07 (P = 0.002). The post
      treatment mean +/- SEM values in xylazine group were 2.18 +/- 0.97 (P < 0.001)
      and 2.62 +/- 1.17 (P = 0.001) at 15 and 25 min respectively. Comparison between
      T(15) and T(25) in acepromazine group (P = 0.49) and xylazine group (P = 0.56)
      revealed no significant differences. CONCLUSION: These observations indicate that
      both acepromazine or xylazine significantly reduced tear production in clinically
      normal cats. In cats, clinicians should measure STT values prior to utilizing
      acepromazine or xylazine as sedatives in order to accurately assess the results.
      Moreover, sterile ocular lubricant or tear replacement should be used as a
      corneal protectant during sedation with these drugs.

PMID- 20149166
TI  - Assessment of a 27-kDa antigen in enzyme-linked immunosorbent assay for the
      diagnosis of fasciolosis in Vietnamese patients.
AB  - Fasciolosis has emerged as an important zoonotic disease in many parts of the
      world. In recent years, an increasing number of human cases were reported in
      Vietnam. In this study, the 27-kDa component protein from the excretory/secretory
      production of adult Fasciola gigantica, purified by high performance liquid
      chromatography, was assessed in an enzyme-linked immunosorbent assay (ELISA) to
      detect antibodies against Fasciola spp. for diagnosis of human fasciolosis. The
      ELISA showed a high sensitivity (100%) and specificity (97.67%) when tested on
      patients with fasciolosis, other parasitic infections, cholangiocarcinoma and on
      healthy controls. The assay was applied for diagnosis on 143 patients in the Viet
      Duc-Hanoi hospital who presented with clinical signs of liver disease and lesions
      in their livers as shown by imaging techniques. Antibodies were found in 37
      (25.9%) of these patients, of whom only 3 shed Fasciola eggs in their stools
      (2.1%). The excellent response to triclabendazole treatment of 37 sero-positive
      patients confirmed the diagnosis of fasciolosis. This study demonstrated the
      diagnostic potential for human fasciolosis of the 27-kDa antigen ELISA.
      Fasciolosis should be considered in the differential diagnosis of hepatic disease
      in Vietnam.

PMID- 20149169
TI  - Canine pre-iridal fibrovascular membranes: morphologic and immunohistochemical
      investigations.
AB  - OBJECTIVE: Pathologic intraocular neovascularization is a key component of many
      canine ophthalmic diseases such as uveitis, retinal detachment, intraocular
      neoplasms, and corneal perforation. The purpose of this study was to evaluate the
      structure of pre-iridal fibrovascular membranes (PIFMs) associated with several
      different disease processes and to identify specific factors associated with
      their development in the canine eye. PROCEDURE: This study examined 36 enucleated
      canine eyes with the diagnosis of PIFM and one of the following: lens-induced
      uveitis, retinal detachment, iridociliary adenoma, corneal perforation, severe
      hyphema, or vitreal gliovascular membranes (canine ocular gliovascular syndrome,
      COGS). Three histologic stains and six immunohistochemical stains were performed
      in all 36 PIFM eyes and four histologically normal eyes, including: hematoxylin
      and eosin, alcian blue periodic acid schiff (PAS), Masson's trichrome, platelet
      endothelial cell adhesion molecule-1 (CD31), smooth muscle actin, vimentin,
      laminin, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2).
      RESULTS: Pre-iridal fibrovascular membrane extracellular matrix staining was
      consistent with collagen and mucins in all cases and positive for laminin in most
      cases. All PIFMs contained CD31-positive vessels and predominantly
      lymphoplasmacytic inflammation. Both PIFM vessels and spindle cells were positive
      for laminin, vimentin, smooth muscle actin, VEGF, and COX-2. Secondary
      intraocular pathology and immunohistochemical staining of other intraocular
      structures are also reported. CONCLUSIONS: Pre-iridal fibrovascular membrane
      morphology and immunohistochemical characteristics were similar across six canine
      disease processes, suggesting analogous pathophysiologic mechanisms. COX-2 and
      VEGF were identified using immunohistochemistry and may play a role in PIFM
      development.

PMID- 20149170
TI  - Effect of three treatment protocols on acute ocular hypertension after
      phacoemulsification and aspiration of cataracts in dogs.
AB  - OBJECTIVE: To compare the effect of topical latanoprost, intracameral carbachol,
      or no adjunctive medical therapy on the development of acute postoperative
      hypertension (POH) and inflammation after routine phacoemulsification and
      aspiration (PA) of cataracts in dogs. DESIGN: Retrospective study. PROCEDURES:
      Dogs received either one drop of topical 0.005% latanoprost (21 dogs, 39 eyes),
      an intracameral injection of 0.3 mL of 0.01% carbachol (15 dogs, 30 eyes), or no
      adjunctive therapy (46 dogs, 90 eyes) immediately following PA of cataract(s).
      Intraocular pressure (IOP) was measured in all dogs 2 and 4 h after surgery. IOP
      was measured and aqueous flare assessed at 8 am the day after surgery. RESULTS:
      Carbachol-treated dogs had significantly higher mean IOP (33.2 +/- SD 20.8 mmHg)
      2 h after surgery than dogs receiving no adjunctive therapy (22.0 +/- SD 14.1
      mmHg) (P = 0.049). There were no significant differences in IOP among groups at
      any other time point. There were no significant differences in number of POH
      episodes between dogs treated with carbachol (47%), latanoprost (29%), or dogs
      that received no adjunctive therapy (33%). There were no significant differences
      in mean aqueous flare grade between eyes treated with latanoprost (1.7 +/- SD
      0.4) or carbachol (1.4 +/- SD 0.6), and eyes that received no adjunctive therapy
      (1.7 +/- SD 0.4). CONCLUSIONS: Topical 0.005% latanoprost or intracameral
      injection of 0.3 mL of 0.01% carbachol after PA in dogs did not reduce POH or
      increase intraocular inflammation compared to dogs not receiving adjunctive
      therapy after PA of cataracts.

PMID- 20149171
TI  - Radiotherapy for canine chronic superficial keratitis using soft X-rays (15 kV).
AB  - OBJECTIVE: To evaluate the effect of soft X-ray therapy in the treatment of
      refractory chronic superficial keratitis (CSK). ANIMALS STUDIED: Thirteen dogs
      with severe CSK, that had been refractory to prior medical and/or surgical
      therapy were treated with soft X-ray therapy. PROCEDURES: Both corneas of each
      dog were irradiated with soft X-rays (15 kV), to a total dose of 30 Gy,
      administered as two fractions over 48-96 h. Treatment was carried out under deep
      sedation in all dogs. Three dogs were treated by superficial lamellar keratectomy
      48 h prior to radiotherapy. Changes in the extent of corneal pigmentation,
      pigment density and corneal vascularization were documented using a semi
      quantitative grading scheme, schematic drawings and clinical photographs.
      RESULTS: Only minor, transient adverse effects of treatment, such as photophobia,
      epiphora and blepharitis were noted. Overall the effect of soft X-rays on the
      course of the keratitis was superior when compared to the effect of Sr-90
      irradiation that had been determined in a previous study. CONCLUSION: Soft X-ray
      irradiation combined with keratectomy is a safe and effective new treatment
      option for severe and advanced CSK with significant visual impairment due to
      corneal pathology.

PMID- 20149172
TI  - Periocular cutaneous mast cell tumors in cats: evaluation of surgical excision
      (33 cases).
AB  - OBJECTIVE: To describe feline periocular cutaneous mast cell tumor (CMCT)
      clinical features, rates of local tumor recurrence and metastases, and cat
      survival time following surgical excision. ANIMALS STUDIED: Thirty-three cats
      with periocular CMCTs. PROCEDURES: Medical records of cats diagnosed with
      periocular CMCTs were reviewed; cats were included if CMCTs were surgically
      excised and the diagnosis confirmed by histopathology. The appearance, size,
      location and histopathology findings of CMCTs were recorded. Rates of local
      recurrence, metastasis, and survival time following surgical excision were
      collected when available. RESULTS: All periocular CMCTs were restricted to the
      eyelids. In addition to surgical excision, three cats were treated with
      adjunctive therapy (strontium-90 irradiation or cryotherapy) intraoperatively.
      Local tumor control was achieved in 22/23 cats with a minimum follow-up of 30
      days (median follow-up time of 711 days); one cat developed disseminated CMCTs
      but no local recurrence. Cats with periocular CMCTs had a median survival time of
      945 days. Metastatic disease involving peripheral lymph nodes or abdominal
      viscera was not detected in any cat at any time during the study. All periocular
      CMCTs were classified as low-grade based on histopathology, and complete excision
      was achieved in approximately 50% of cases. CONCLUSIONS: Surgical excision of
      periocular CMCTs in cats is an effective treatment option with rare local
      recurrence and metastases, even following incomplete surgical excision.

PMID- 20149173
TI  - Evaluation of a rebound tonometer (Tonovet) in clinically normal cat eyes.
AB  - OBJECTIVE: To determine the accuracy of and to establish reference values for a
      rebound tonometer (Tonovet) in normal feline eyes, to compare it with an
      applanation tonometer (Tonopen Vet) and to evaluate the effect of topical
      anesthesia on rebound tonometry. PROCEDURES: Six enucleated eyes were used to
      compare both tonometers with direct manometry. Intraocular pressure (IOP) was
      measured in 100 cats to establish reference values for rebound tonometry. Of
      these, 22 cats were used to compare rebound tonometry with and without topical
      anesthesia and 33 cats to compare the rebound and applanation tonometers. All
      evaluated eyes were free of ocular disease. RESULTS: Both tonometers correlated
      well with direct manometry. The best agreement with the rebound tonometer was
      achieved between 25-50 mmHg. The applanation tonometer was accurate at pressures
      between 0 and 30 mmHg. The mean IOP in clinically normal cats was 20.74 mmHg with
      the rebound tonometer and 18.4 mmHg with the applanation tonometer. Topical
      anesthesia did not significantly affect rebound tonometry. CONCLUSIONS: As the
      rebound tonometer correlated well with direct manometry in the clinically
      important pressure range and was well tolerated by cats, it appears suitable for
      glaucoma diagnosis. The mean IOP obtained with the rebound tonometer was 2-3 mmHg
      higher than that measured with the applanation tonometer. This difference is
      within clinically acceptable limits, but indicates that the same type of
      tonometer should be used in follow-up examinations in a given cat.

PMID- 20149174
TI  - Isolation and cultivation of equine corneal keratocytes, fibroblasts and
      myofibroblasts.
AB  - OBJECTIVE: To establish an in vitro model for the investigation of equine corneal
      wound healing. To accomplish this goal, a protocol to isolate and culture equine
      corneal keratocytes, fibroblasts and myofibroblasts was developed. ANIMAL
      MATERIAL: Equine corneal buttons were aseptically harvested from healthy research
      horses undergoing humane euthanasia for reasons unrelated to this study. Slit
      lamp biomicroscopy was performed prior to euthanasia by a board-certified
      veterinary ophthalmologist to ensure that all samples were harvested from horses
      free of anterior segment disease. PROCEDURE: Equine corneal stroma was isolated
      using mechanical techniques and stromal sub-sections were then cultured.
      Customized media at different culture conditions was used to promote growth and
      differentiation of corneal stromal cells into keratocytes, fibroblasts and
      myofibroblasts. RESULTS: Cell culture techniques were successfully used to
      establish a method for the isolation and culture of equine corneal keratocytes,
      fibroblasts and myofibroblasts. Immunohistochemical staining for alpha-smooth
      muscle and F-actin was used to definitively differentiate the three cell types.
      CONCLUSION: Equine corneal stromal keratocytes, fibroblasts and myofibroblasts
      can be predictably isolated and cultured in vitro using this protocol.

PMID- 20149175
TI  - Feline conjunctival melanoma: histopathological characteristics and clinical
      outcomes.
AB  - PURPOSE: We report on the histopathology and clinical features of 21 cases of
      feline conjunctival melanoma. METHODS: A total of 18 cases are from the COPLOW
      collection and three cases from Antech Diagnostics. We tabulated the location of
      the tumor, pigmentation, cell shape, mitotic index and presence of multinucleated
      tumor cells. Surveys were sent to referring ophthalmologists to obtain further
      information about each case. RESULTS: The mean age of the cats was 12.4 years. A
      total of 11 cases were neutered males, six spayed females, and one each of intact
      female and male. Thirteen of the 21 cases were located on the bulbar conjunctiva,
      three on third eyelid only, three on palpebral conjunctiva. Sixteen tumors were
      pigmented while five were amelanotic. Seventeen of the cases consisted of round
      cell only while four cases were mixed populations of round and spindle cell.
      Fourteen of the cases contained multinucleated cells. The mitotic index ranged
      from 0 to 45 mitotic figures/10 HPF. Of the 13 cases with adequate follow-up
      information, four showed local recurrence while three reported metastasis. Eight
      cats had died at the time of the survey. Survival time post-diagnosis ranged from
      0.5 to 36 months. Two cases had metastasized to the submandibular lymph nodes and
      in a third case, an abdominal mass was detected. CONCLUSIONS: Feline conjunctival
      melanoma is most frequently found on the bulbar conjunctiva, are mostly round
      cells and suggest that conjunctival melanoma in cats has a poorer long term
      prognosis than the same neoplasm in dogs.

PMID- 20149176
TI  - A keratoprosthesis prototype for the dog.
AB  - OBJECTIVE: To describe the technique for implantation of a novel keratoprosthesis
      (KP) prototype and evaluate its application for the treatment of corneal
      blindness in dogs. ANIMALS STUDIED: Seven dogs, all of them being clinically
      blind before surgery as a result of severe corneal endothelial disease (5/7) or
      chronic superficial keratitis (2/7) that were unresponsive to prior therapy.
      PROCEDURES: A silicone KP was implanted unilaterally, just anterior to Descemet's
      membrane, after creating a stromal pocket by deep stromal lamellar dissection.
      RESULTS: Implantation of the KP was accomplished without complication in six of
      seven operated dogs. In the remaining case, an intra-operative complication
      (perforation of Descemet's membrane) was associated with extrusion of the KP 8
      weeks postoperatively. All operated eyes regained limited vision after surgery.
      Three to six months after implantation purulent keratitis occurred in all five
      eyes with endothelial disease, necessitating surgical removal of the KP 6 months
      postoperatively in 5/7 eyes. CONCLUSIONS: This KP prototype shows promise as a
      treatment for certain blinding corneal diseases. However, changes in the design
      of this KP, allowing improved stromal integration, will be necessary before its
      clinical application can be approved.

PMID- 20149177
TI  - Coccidioides posadasii keratouveitis in a llama (Lama glama).
AB  - A 7-year-old male llama was examined for a 3-month history of weight loss, and
      unilateral keratouveitis. Clinical examination revealed nonulcerative corneal
      stromal abscessation, corneal vascularization, corneal edema, miosis, posterior
      synechia, cataract, and fibrin in the anterior chamber of the right eye. The left
      eye was normal. Histopathology of the right eye following enucleation revealed
      pyogranulomatous keratouveitis with intralesional fungal spherules consistent
      with Coccidioides spp. PCR amplification with DNA sequencing confirmed
      Coccidioides posadasii infection. To the authors' knowledge, this is the first
      reported case of ocular coccidioidomycosis in a llama.

PMID- 20149178
TI  - Ocular myxoid leiomyosarcoma in a cat.
AB  - A case of myxoid leiomyosarcoma likely of iris dilator muscle origin in the
      enucleated eye of a 6-year-old domestic short haired cat is reported. The poorly
      demarcated mass expanded the iris, partially filled the globe and extended into
      the optic nerve. The mass was composed of spindle cells separated by abundant
      matrix positive for mucopolysaccharides with alcian blue. The neoplastic cells
      were immunoreactive for smooth muscle actin (SMA), S100 and vimentin, and
      negative for cytokeratin, Melan-A, glial fibrillary protein (GFAP) and desmin.
      There was no evidence of recurrence or metastasis 6 months after enucleation.

PMID- 20149179
TI  - Co-existing squamous cell carcinoma and hemangioma on the ocular surface of a
      cat.
AB  - A 14-year-old spayed female domestic short-haired cat was presented for
      evaluation of a mass in the right eye. Ophthalmic examination revealed a blind
      right eye and presence of two distinct masses: a pink and a red-to-brown mass,
      the latter occupying most of the cornea and part of the conjunctiva. Exenteration
      was performed under general anesthesia, and the ocular tissues were processed
      routinely for histopathology. Upon microscopic examination, a malignant
      epithelial neoplasm and a benign vascular neoplasm were present in the cornea.
      The conjunctiva and the third eyelid were also affected. Upon
      immunohistochemistry, the epithelial tumor was positive for cytokeratin and
      negative for vimentin and the endothelial tumor was negative for cytokeratin and
      positive for vimentin. A diagnosis of squamous cell carcinoma (SCC) and
      hemangioma was made. The SCC was affecting the cornea, bulbar conjunctiva
      (lateral and inferior) and the base of the third eyelid, whereas the hemangioma
      was affecting the cornea and medial limbus. To the authors' knowledge, this is
      the first report of concomitant SCC and hemangioma affecting the ocular surface
      in a cat.

PMID- 20149181
TI  - Concerning a cat with a mycobacterial granuloma situated on the cornea.

PMID- 20149183
TI  - The potential of genetically-modified pig mesenchymal stromal cells in
      xenotransplantation.

PMID- 20149184
TI  - Can human viruses infect porcine xenografts?
AB  - Xenotransplantation exposes the recipient to known and unknown pathogens of the
      donor pig (donor-derived xenosis). A major effort has been undertaken to minimize
      the risk of transmission from the donor using specialized breeding techniques.
      With the exception of endogenous retroviruses and porcine lymphotropic
      herpesvirus, exclusion of known pathogens was successful and has eliminated a
      majority of donor pathogens. In the recipient, enhanced replication of many
      pathogens will be stimulated by the immune responses induced by transplantation
      and by the immune suppression used to prevent graft rejection. Infection of the
      graft may occur with unpredictable consequences due to the cross-species
      situation. Infectivity may be decreased as entry or replication is altered by
      missing receptors or inability to use the cellular machinery. Replication of
      organisms in the xenograft and the inability of the human host to respond to
      human pathogens in the context of a xenograft infection due to immune
      suppression, or the presentation of such pathogens in the context of pig instead
      of human major histocompatibility complex (MHC) could impair control of such
      infections. Recent data suggest that some human herpesviruses infections, such as
      human cytomegalovirus, may infect porcine tissue and are associated with a pro
      inflammatory phenotype. This review focuses on human or recipient-derived
      pathogens and their potential harmful role in xenograft infection.

PMID- 20149185
TI  - Complement regulation in the GalT KO era.
AB  - A number of institutes have reported on the successful production of alpha
      galactosyltransferase knockout (GalT-KO) pigs. After producing such pigs,
      hyperacute rejection appeared to no longer be a problem. However, acute vascular
      rejection (AVR)/acute humoral xenograft rejection (AHXR) is defined as a
      rejection that begins within 24 h after transplantation and gradually destroys
      the graft. The origin of AVR/AHXR continues to be a controversial topic, but is
      generally thought to be initiated by xeno-reactive antibodies, including non-Gal
      antibodies and subsequent activation of the graft endothelium, the complement and
      the coagulation systems. The complement is activated via the classical pathway by
      non-Gal antigens and ischemia-reperfusion injury, via the alternative pathway,
      especially on islets, and via the lectin pathway. Therefore the complement system
      is still an important recognition and effector mechanism of AVR/AHXR. In
      addition, quite recently, based on the relationship between complement and
      coagulation systems, a new pathway has been proposed. All complement regulatory
      proteins (CRPs) have the ability to regulate complement activation in different
      ways. Therefore, to effectively protect xenografts against AVR/AHXR, it appears
      reasonable to employ not only one but several CRPs including anti-complement
      drugs. Non-Gal antigens, such as the Hanganutziu-Deicher antigen, is still
      present on GalT-KO grafts. The further assessment of antigens continues to be an
      important issue in the area of clinical xenotransplantation. The above
      conclusions suggest that the expression of human CRPs on GalT-KO grafts is
      necessary. Moreover, multilateral inhibition of complement activation is required
      in conjunction with the regulation of the coagulation system.

PMID- 20149186
TI  - Potential value of human thrombomodulin and DAF expression for coagulation
      control in pig-to-human xenotransplantation.
AB  - BACKGROUND: Problems of coagulation disorder remain to be resolved in pig-to
      primate xenotransplantation. Molecular incompatibilities in the coagulation
      systems between pigs and humans, such as the thrombomodulin (TM)-protein C system
      or direct prothrombinase activity, have been suggested as possible causes.
      Coagulation and complement activation are closely related to each other. The
      purpose of this study was to elucidate the protective effects on the coagulation
      system of the expression of human TM and decay accelerating factor (hDAF) (for
      inhibition of complement activation) in pig endothelial cells. METHODS: Human
      aortic endothelial cells (HAEC), porcine aortic endothelial cells (PAEC), hDAF
      expressing PAEC (hDAF-PAEC), hDAF/Endo-beta-galactosidase C-expressing PAEC
      (hDAF/EndoGalC-PAEC), hTM-expressing PAEC (hTM-PAEC), hDAF/hTM expressing-PAEC
      (hDAF/hTM-PAEC), and hDAF/EndoGalC/hTM-expressing PAEC (hDAF/EndoGalC/hTM-PAEC)
      were used in this study. Coagulation activity was examined by clotting, activated
      protein C (APC), and thrombin generation assay. RESULTS: A large difference was
      observed in clotting time of human plasma when exposed to PAEC (170 s) and HAEC
      (1020 s). hTM expression on PAEC was proven to produce a comparable level of APC
      to that produced by HAEC, which prolonged the clotting time, though not to the
      level of HAEC. Pretreatment with human sera considerably shortened the clotting
      time in PAEC (80 s). hDAF-PAEC significantly inhibited such a shortening of
      clotting time by reductions in tissue factor expression and thrombin generation.
      Thrombin generation through direct prothrombinase activity, which was detected
      only in PAEC, could be suppressed by hTM expression. Suppression of antibody
      binding and complement activation improved clotting time not in PAEC, but in PAEC
      expressing hTM. CONCLUSIONS: In addition to effective suppression of antibody
      induced complement activation, hTM expression in PAEC may be essential for
      regulating procoagulant activity in xenotransplantation.

PMID- 20149187
TI  - Surgical angiogenesis: a new approach to maintain osseous viability in
      xenotransplantation.
AB  - BACKGROUND: Large segmental osseous defects are challenging clinical problems.
      Current reconstructive methods, using non-viable allografts, vascularized
      autografts or prostheses have significant rates of serious complications and
      failure. These include infection, stress fracture and non-union (frozen
      structural allogenic bone); loosening and implant failure (prosthetic
      replacement); limited availability, poor match of size and shape and donor site
      morbidity (vascularized autograft bone). In the future, microvascular
      transplantation of living allogenic or xenogenic bone could solve some of these
      issues, combining the advantages of living bone autografts (capability of primary
      osseous healing, remodeling, and fracture resistance) with the ability to match
      size and shape, provide immediate stability and avoid donor site morbidity.
      Xenotransplants would be particularly attractive, as they could be readily
      available, if long-term bone survival could be achieved without unacceptable
      morbidity. Here, we present a preliminary study to evaluate a new and unique
      method to maintain xenogenic bone circulation without need for long-term immune
      modulation that depends upon generation of a neo-angiogenic circulation within
      the transplanted bone from recipient-derived vessels. Thus, only short-term
      immunosuppression would be required to achieve bone survival. METHODS: One
      hundred and forty-one hamster femora were microsurgically transplanted to rats,
      restoring nutrient vessel circulation with standard microvascular anastomoses. At
      the same time, a host-derived arteriovenous bundle (AVB) was placed within the
      medullary canal. Two independent variables were evaluated: use of
      tacrolimus/cyclophosmamid immunosuppression (IS) and patency of the implanted
      AVB. Rats were therefore randomized to four groups; group 1-no IS + patent AVB;
      group 2-no IS + ligated AVB; group 3-IS + patent AVB; group 4-IS + ligated AVB.
      Rats were sacrificed after 1 or 2 weeks. We evaluated bone blood flow
      (microsphere entrapment), neoangiogenesis (microangiography and quantification of
      capillary density), bone necrosis rate (osteocyte counts) and nutrient pedicle
      rejection (microsurgical anastomotic patency). Statistical Analysis was performed
      with two-way ANOVA with Bonferroni adjustment. Differences were considered
      significant when P < 0.05. RESULTS: Capillary density was significantly increased
      with a patent intramedullary AVB (groups 1/3) compared to groups with ligated
      AVBs (groups 3/4). Capillary sprouting was predominantly restricted to the
      endosteal layer. Most nutrient pedicles (78.7%) stayed patent in groups with IS
      (groups 3 and 4). Consequently, bone blood flow was significantly higher in
      groups 3 and 4 compared to groups 1 and 2. Similarly, a patent AV bundle improved
      flow in group 1 when compared to group 2. The bone necrosis rate was not
      influenced by the presence of patent AVBs but was significantly reduced in groups
      3 and 4. CONCLUSIONS: Surgical angiogenesis occurs when patent arteriovenous
      bundles are placed in the medullary canal of xenogenic bone and leads to
      increased bone blood flow. Bone viability was not significantly influenced by
      neoangiogenesis. Although capillary sprouting was restricted to the endosteal
      layer in this short term study, more complete cortical revascularization might be
      observed in a long-term study. Such a study should further evaluate whether these
      new vessels supply sufficient blood flow to maintain long-term bone viability and
      allow remodeling.

PMID- 20149188
TI  - Structural characterization of alpha1,3-galactosyltransferase knockout pig heart
      and kidney glycolipids and their reactivity with human and baboon antibodies.
AB  - BACKGROUND: alpha1,3-galactosyltranferase knockout (GalT-KO) pigs have been
      established to avoid hyperacute rejection in GalT-KO pig-to-human
      xenotransplantation. GalT-KO pig heart and kidney glycolipids were studied
      focusing on elimination of Gal-antigens and whether novel antigens would appear.
      Non-human primates are used as pre-clinical transplantation experimental models.
      Therefore, sera from baboons transplanted with GalT-KO hearts were compared with
      human serum regarding reactivity with pig glycolipids. METHODS: Neutral and
      acidic glycolipids were isolated from GalT-KO and WT pig hearts and kidneys.
      Glycolipid immune reactivity was tested on TLC plates using human affinity
      purified anti-Gal Ig, anti-blood group monoclonal antibodies, lectins, and human
      serum as well as baboon serum collected before and after GalT-KO pig heart
      transplantations. Selected glycolipid fractions, isolated by HPLC, were
      structurally characterized by mass spectrometry and proton NMR spectroscopy.
      RESULTS: GalT-KO heart and kidney lacked alpha3Gal-terminated glycolipids
      completely. Levels of uncapped N-acetyllactosamine precursor compounds, blood
      group H type 2 core chain compounds, the P1 antigen and the x(2) antigen were
      increased. Human serum antibodies reacted with Gal-antigens and N
      glycolylneuraminic acid (NeuGc) in WT organs of which only the NeuGc reactivity
      remained in the GalT-KO tissues. A clear difference in reactivity between baboon
      and human antibodies with pig glycolipids was found. This was most pronounced for
      acidic, not yet identified, compounds in GalT-KO organs which were less abundant
      or lacking in the corresponding WT tissues. CONCLUSIONS: GalT-KO pig heart and
      kidney completely lacked Gal glycolipid antigens whilst glycolipids synthesized
      by competing pathways were increased. Baboon and human serum antibodies showed a
      different reactivity pattern to pig glycolipid antigens indicating that non-human
      primates have limitations as a human pre-clinical model for immune rejection
      studies.

PMID- 20149189
TI  - Survey of glycoantigens in cells from alpha1-3galactosyltransferase knockout pig
      using a lectin microarray.
AB  - BACKGROUND: Glycoantigens represent major obstacles to successful
      xenotransplantation. Even after the alpha1-3galactosyltransferase (GalT) gene
      knockout (GalT-KO) pigs were produced, non-Gal antigens continue to be present.
      This study reports on lectin blot analyses for endothelial cells (EC) and
      fibroblasts from GalT-KO pigs. METHODS: Differences in glycoantigens that are
      produced on cell surfaces in humans and pigs were surveyed. Differences between
      ECs and fibroblasts from wild-type and GalT-KO pigs were also examined. EC and
      fibroblasts from GalT-KO pigs (heterozygous and homozygous) with N
      acetylglucosaminyltransferase-III (GnT-III), a wild-type EC from the sibling,
      human EC lines, HUVEC (human EC from umbilical veins), & HAOEC (human EC from
      aortas), and human fibroblast line were used. EC and fibroblasts were cultured in
      gelatin-coated dishes for several days. After sonication and centrifugation, the
      supernatant protein from each cell was labeled with Cy3, applied to a lectin
      array and scanned with an SC Profiler, and analyzed using an Array Pro Analyzer.
      RESULTS: The pig EC showed higher signals in Euonymus Europaeus (EEL) & Griffonia
      simplicifolia I-B(4) (GSI-B4), binds alpha-Gal, and in Wisteria Floribunda (WFA),
      Helix pomatia (HPA), Glycine max (SBA), & Griffonia simplicifolia I-A(4) (GSI
      A4), binds GalNAc including the Thomsen-Friedenreich precursor (Tn)-antigen,
      while the human EC showed strong signals in Ulex europaeus I (UEA-I), Maackia
      amurensis (MAL), Erythrina cristagalli (ECA), & Trichosanthes japonica I (TJA-I)
      instead. The EC from the GalT-KO pig signals for EEL & GSI-B4 disappeared and
      those for Bauhinia purpurea alba (BPL), HPA, SBA, & GSI-A4 were greatly
      diminished as well, while it up-regulated signals for Sambucus Nigra (SNA),
      Sambucus sieboldiana (SSA), & TJA-I, bind alpha2-6 sialic acid, compared to the
      wild-type pig EC. Concerning fibroblasts, the signals for HPA, SBA, & GSI-A4 were
      the most intense in the wild-type, and the intensities for homozygous-KO were
      less, approaching those of humans. In addition, the order of the intensities, as
      detected by Arachis hypogaea (PNA) & Maclura pomifera (MPA), binding Galbeta1
      2GalNAc, indicates that the Thomsen-Friedenreich (T)-antigen is likely present on
      pig fibroblasts. CONCLUSION: It is possible that the T-antigen and Tn-antigen
      related to GalNAc are non-Gal antigens, but, fortunately, not only alpha-Gal but
      also GalNAc were found to be decreased in the KO-pig.

PMID- 20149190
TI  - Impaired spinal cord remyelination by long-term cultured adult porcine olfactory
      ensheathing cells correlates with altered in vitro phenotypic properties.
AB  - BACKGROUND: Extensive studies in rodents have identified olfactory ensheathing
      cells (OECs) as promising candidates for cell-based therapies of spinal cord and
      peripheral nerve injury. Previously, we demonstrated that short-term cultured
      adult porcine OECs can remyelinate the rodent and non-human primate spinal cord.
      Here, we studied the impact of the culturing interval on the remyelinating
      capacity of adult porcine OECs. METHODS: Cells were maintained for 1, 2, and 4 to
      6 weeks in vitro prior to transplantation into the demyelinated rat spinal cord.
      Parallel to this, the in vitro phenotypic properties of the OEC preparations used
      for transplantation were analyzed with regard to morphology, low affinity nerve
      growth factor receptor (p75(NTR)) expression and proliferation. RESULTS: We
      report that prolonged culturing of adult porcine OECs resulted in impaired
      remyelination of the adult rat spinal cord. Animals receiving transplants of OECs
      maintained in vitro for 2 weeks displayed significantly less remyelinated axons
      than those animals that received OEC transplants cultured for 1 week. There was
      virtually no remyelination after transplantation of OECs cultured for 4 to 6
      weeks. The adult porcine OECs displayed a progressive lost of p75(NTR)-expression
      as determined by immunostaining and flow cytometry with time in culture.
      CONCLUSIONS: Taken together, the results indicate that porcine OECs undergo
      systematic changes with time in culture that result in reduced p75(NTR)
      expression, decreased proliferation, and reduced remyelinating capability with
      time in vitro indicating that relatively short term cultures with limited
      expansion would be required for transplantation studies.

PMID- 20149191
TI  - Enrichment of xenograft-competent genetically modified pig cells using a targeted
      toxin, isolectin BS-I-B4 conjugate.
AB  - BACKGROUND: The recent availability of alpha-1,3-galatosyltransferase knockout
      pigs has eliminated anti-Gal antibodies to the galalpha1-3gal (alphagal epitope)
      as the major barrier to xenotransplantation. These alphagal epitope-negative
      animals can also be produced by somatic cell nuclear transfer of cells
      overexpressing endo-beta-galactosidase (EndoGalC), an enzyme capable of digesting
      the alphagal epitope. For this, selection of cells with highly reduced synthesis
      of alphagal epitope is a prerequisite. In this study, we developed a novel method
      of selection using isolectin BS-I-B(4)-conjugated saporin (IB4-SAP), a targeted
      cytotoxin, that is specific for the terminal alphagal epitope. METHODS: A mixture
      of alphagal epitope-expressing and non-expressing pig cells was obtained by
      transfection with an EndoGalC expression vector. These cells were incubated with
      a solution containing IB4-SAP for 2 h at 37 degrees C, and subsequently
      cultivated for over 2 months under general conditions. RESULTS: Almost all (98%)
      of surviving cells were completely negative for expression of alphagal epitope,
      as confirmed by cytochemical staining using fluorescence-labeled IB4. FACS
      analysis also confirmed that the IB4-SAP-treated cells exhibited a staining
      pattern similar to that of the IB4-negative human cells. Extended cultivation
      (more than 6 months) of these IB4-SAP-treated cells did not alter the above
      staining pattern. RT-PCR analysis revealed the presence of EndoGalC mRNA in these
      cells. CONCLUSIONS: This IB4-SAP-mediated method of selection of alphagal epitope
      negative cells will provide an alternative to the present method of cytotoxicity
      based selection using specific antibody and complement.

PMID- 20149194
TI  - Selenium and prostate cancer.

PMID- 20149195
TI  - Plastic meatotomy for pure meatal stenosis in patients with lichen sclerosus.

PMID- 20149200
TI  - Seduced by a robot.

PMID- 20149201
TI  - You can't resist the charms of the robot!

PMID- 20149202
TI  - The robotic revolution: the seduction continues.

PMID- 20149203
TI  - Current state of urological cryosurgery: prostate and kidney.

PMID- 20149205
TI  - We need to learn to love the pharmaceutical industry.

PMID- 20149204
TI  - The presence of prostate cancer on saturation biopsy can be accurately predicted.
AB  - OBJECTIVE: To improve the ability of our previously reported saturation biopsy
      nomogram quantifying the risk of prostate cancer, as the use of office-based
      saturation biopsy has increased. PATIENTS AND METHODS: Saturation biopsies of 540
      men with one or more previously negative 6-12 core biopsies were used to develop
      a multivariable logistic regression model-based nomogram, predicting the
      probability of prostate cancer. Candidate predictors were used in their original
      or stratified format, and consisted of age, total prostate-specific antigen (PSA)
      level, percentage free PSA (%fPSA), gland volume, findings on a digital rectal
      examination, cumulative number of previous biopsy sessions, presence of high
      grade prostatic intraepithelial neoplasia on any previous biopsy, and presence of
      atypical small acinar proliferation (ASAP) on any previous biopsy. Two hundred
      bootstraps re-samples were used to adjust for overfit bias. RESULTS: Prostate
      cancer was diagnosed in 39.4% of saturation biopsies. Age, total PSA, %fPSA,
      gland volume, number of previous biopsies, and presence of ASAP at any previous
      biopsy were independent predictors for prostate cancer (all P < 0.05). The
      nomogram was 77.2% accurate and had a virtually perfect correlation between
      predicted and observed rates of prostate cancer. CONCLUSIONS: We improved the
      accuracy of the saturation biopsy nomogram from 72% to 77%; it relies on three
      previously included variables, i.e. age, %fPSA and prostate volume, and on three
      previously excluded variables, i.e. PSA, the number of previous biopsy sessions,
      and evidence of ASAP on previous biopsy. Our study represents the largest series
      of saturation biopsies to date.

PMID- 20149209
TI  - Impact of ethnicity on surgical margins at radical prostatectomy.

PMID- 20149207
TI  - High-intensity focused ultrasound for localized prostate cancer: initial
      experience with a 2-year follow-up.

PMID- 20149210
TI  - Repair of giant vesico-vaginal fistulae using a rotational bladder flap with or
      without a gracilis flap.

PMID- 20149214
TI  - Alterations in the salivary proteome associated with periodontitis.
AB  - AIM: To identify changes in the salivary proteome associated with active
      periodontitis. MATERIALS AND METHODS: Quantitative proteomics (two-dimensional
      sodium dodecyl sulphate polyacrylamide gel electrophoresis) was used to
      investigate whole saliva from individuals with severe periodontitis and their
      proteomic profiles before and after periodontal treatment were compared. RESULTS:
      A comparison of 128 proteins across all saliva samples identified 15 protein
      spots with altered abundance. The predominant alteration observed was an increase
      in the abundance of the S100 proteins S100A8/A9/A6. Of the remaining proteins
      with altered abundance, haptoglobin, prolactin inducible protein and parotid
      secretory protein have previously been associated with host defence. CONCLUSION:
      These results highlight the predominant involvement of S100 proteins in the host
      response during periodontitis, identify host defence components that have not
      been linked previously to this disease and suggest new potential biomarkers for
      monitoring disease activity in periodontitis.

PMID- 20149215
TI  - The essential role of toll like receptor-4 in the control of Aggregatibacter
      actinomycetemcomitans infection in mice.
AB  - OBJECTIVE: Aggregatibacter actinomycetemcomitans is an oral Gram-negative
      bacterium that contributes to periodontitis progression. Isolated antigens from
      A. actinomycetemcomitans could be activating innate immune cells through Toll
      like receptors (TLRs). In this study, we evaluated the role of TLR4 in the
      control of A. actinomycetemcomitans infection. MATERIAL AND METHODS: We examined
      the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced
      periodontal disease in TLR4(-/-) mice. The production of cytokines was evaluated
      by ELISA. The bacterial load was determined by counting the number of colony
      forming units per gram of tissue. RESULTS: The results showed that TLR4-deficient
      mice developed less severe periodontitis after A. actinomycetemcomitans
      infection, characterized by significantly lower bone loss and inflammatory cell
      migration to periodontal tissues. However, the absence of TLR4 facilitated the A.
      actinomycetemcomitans dissemination. Myeloperoxidase activity was diminished in
      the periodontal tissue of TLR4(-/-) mice. We observed a significant reduction in
      the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)
      1beta in the periodontal tissue of TLR4(-/-) mice. CONCLUSION: The results of
      this study highlighted the role of TLR4 in controlling A. actinomycetemcomitans
      infection.

PMID- 20149216
TI  - Fcgamma receptor polymorphisms and their association with periodontal disease: a
      meta-analysis.
AB  - AIM: A systematic review and a meta-analysis were conducted in order to
      investigate the potential association of Fcgamma receptor (FcgammaR)
      polymorphisms with susceptibility to aggressive and chronic periodontal disease.
      MATERIALS AND METHODS: A database search yielded a total of 17 studies involving
      1685 cases and 1570 controls. Three polymorphisms were included in the meta
      analysis: FcgammaRIIA H131R (rs1801274), FcgammaRIIIA F158V (rs396991) and
      FcgammaRIIIB NA1/NA2. Random-effect models were used in the analysis. Odds ratios
      (ORs) along with their 95% confidence intervals (CIs) were computed to compare
      the distribution of alleles and genotypes between cases and controls. RESULTS AND
      CONCLUSIONS: The FcgammaRIIIB NA1/NA2 polymorphism was associated with both
      aggressive (per-allele OR 2.005, 95% CI: 1.044, 3.851) and chronic periodontitis
      (recessive contrast NA2NA2 versus NA1NA1+NA1NA2 OR 1.397, 95% CI: 1.039, 1.878).
      The analysis showed weak evidence for association between the FcgammaRIIA H131R
      polymorphism and aggressive periodontitis in Asians (R versus H allele OR 1.579,
      95% CI: 1.025, 2.432). On the contrary, no relationship was identified between
      FcgammaRIIIA F158V and periodontal disease. Accumulating evidence from basic
      research makes the suggested association between FcgammaRIIIB NA1/NA2
      polymorphism and periodontitis biologically plausible. Further research, however,
      is needed in order to assess possible gene-gene or gene-environment interactions
      (i.e. with smoking).

PMID- 20149217
TI  - Mechanics of sucking: comparison between bottle feeding and breastfeeding.
AB  - BACKGROUND: There is very little evidence of the similarity of the mechanics of
      maternal and bottle feeding. We assessed the mechanics of sucking in exclusive
      breastfeeding, exclusive bottle feeding, and mixed feeding. The hypothesis
      established was that physiological pattern for suckling movements differ
      depending on the type of feeding. According to this hypothesis, babies with
      breastfeeding have suckling movements at the breast that are different from the
      movements of suckling a teat of babies fed with bottle. Children with mixed
      feeding mix both types of suckling movements. METHODS: Cross-sectional study of
      infants aged 21-28 days with only maternal feeding or bottle feeding (234 mother
      infant pairs), and a randomized open cross-over field trial in newborns aged 21
      28 days and babies aged 3-5 months with mixed feeding (125 mother-infant pairs).
      Primary outcome measures were sucks and pauses. RESULTS: Infants aged 21-28 days
      exclusively bottle-fed showed fewer sucks and the same number of pauses but of
      longer duration compared to breastfeeding. In mixed feeding, bottle feeding
      compared to breastfeeding showed the same number of sucks but fewer and shorter
      pauses, both at 21-28 days and at 3-5 months. The mean number of breastfeedings
      in a day (in the mixed feed group) was 5.83 +/- 1.93 at 21-28 days and 4.42 +/-
      1.67 at 3-5 months. In the equivalence analysis of the mixed feed group, the 95%
      confidence interval for bottle feeding/breastfeeding ratio laid outside the range
      of equivalence, indicating 5.9-8.7% fewer suction movements, and fewer pauses,
      and shorter duration of them in bottle feeding compared with breastfeeding.
      CONCLUSIONS: The mechanics of sucking in mixed feeding lay outside the range of
      equivalence comparing bottle feeding with breastfeeding, although differences
      were small. Children with mixed feeding would mix both types of sucking movements
      (breastfeeding and bottle feeding) during the learning stage and adopt their own
      pattern.

PMID- 20149218
TI  - Estrogen receptor positive breast cancers in BRCA1 mutation carriers: clinical
      risk factors and pathologic features.
AB  - INTRODUCTION: Most breast cancers that occur in women with germline BRCA1
      mutations are estrogen receptor-negative (ER-) and also typically lack expression
      of progesterone receptor (PR) and HER2 overexpression. We undertook a study to
      assess the clinical factors that predict for an estrogen receptor positive (ER+)
      breast cancer in BRCA1 mutation carriers and to characterize the pathologic
      features of these tumors. METHODS: Clinical characteristics of BRCA1 carriers
      with 58 ER+ and 114 ER- first invasive breast cancers were compared. Pathologic
      features of BRCA1 ER+ cancers were compared to those of BRCA1 ER- cancers and to
      age-matched ER+ sporadic cancers. RESULTS: BRCA1 carriers aged > or = 50 at
      diagnosis of first invasive breast cancer were more likely to have an ER+ cancer
      compared to those aged < 50 (57% vs 29%, P = 0.005). ER+ BRCA1 cancers were less
      likely than ER- BRCA1 cancers to have "BRCA-associated" features such as high
      mitotic activity, geographic necrosis/fibrotic focus, and pushing margins (RR
      0.06, 0.22, 0.24; P < 0.001, 0.02, 0.03 respectively). When compared to sporadic
      ER+ cancers, ER+ BRCA1 cancers were more often of invasive ductal type (RR 2.4, P
      = 0.03), with a high mitotic rate (RR 5.0, P = 0.006) and absent or mild
      lymphocytic infiltrate (RR 10.2, P = 0.04). CONCLUSIONS: BRCA1 carriers who are
      older at first breast cancer diagnosis are more likely to have ER+ tumors than
      younger BRCA1 carriers. These ER+ cancers appear pathologically "intermediate"
      between ER- BRCA1 cancers and ER+ sporadic breast cancers raising the possibility
      that either some ER+ BRCA1 cancers are incidental or that there is a unique
      mechanism by which these cancers develop.

PMID- 20149219
TI  - Gender differences in specialty preference and mismatch with real needs in
      Japanese medical students.
AB  - BACKGROUND: The shortage of doctors and maldistribution among specialties are of
      great concern in the Japanese health care system. This study investigated
      specialty preference in medical students of one university, and examined gender
      differences and compared their preference with real needs. METHODS: We conducted
      a self-administered questionnaire including specialty preference in all students
      of one medical university. Preference was assessed by the five-level probability
      of their future choice: 1 = very low, 2 = low, 3 = moderate, 4 = high, and 5 =
      very high. The proportion of 4 or 5 was calculated as the preference rate. The
      real needs (magnitude of doctor shortage) in the prefecture were drawn from two
      different surveys. The relationship between the sex-specific preference rate by
      specialty and real needs was assessed by Spearman's correlation coefficient.
      RESULTS: Internal medicine showed the highest preference rate, followed by
      general surgery, pediatrics, and emergency medicine. There was no significant
      correlation between the preference rates of men and women (r = 0.27, p = 0.34).
      The preference rates for general surgery, orthopedics, neurosurgery, and
      emergency medicine were significantly higher in men than in women, while those of
      obstetrics & gynecology, pediatrics, and dermatology were significantly higher in
      women. The magnitude of doctor shortage by specialty from two surveys were
      significantly correlated with the total preference rate and men's preference rate
      (r = 0.54 to 0.74), but not with women's preference rate (r = 0.06 and 0.32).
      CONCLUSIONS: This study elucidated not only gender differences in specialty
      preference but also the relationship to real needs. Critical gender differences
      and mismatch with real needs were found in women. In addition to traditional
      gender roles and insufficient support for women's participation in Japan, gender
      differences and mismatch influence the current and future maldistribution of
      specialties. Systematic changes in the working environment in medical society are
      required to solve these problems.

PMID- 20149221
TI  - Antecedents of teenage pregnancy from a 14-year follow-up study using data
      linkage.
AB  - BACKGROUND: Many western nations continue to have high rates of teenage
      pregnancies and births, which can result in adverse outcomes for both mother and
      child. This study identified possible antecedents of teenage pregnancy using
      linked data from administrative sources to create a 14-year follow-up from a
      cross-sectional survey. METHODS: Data were drawn from two sources - the 1993
      Western Australian Child Health Survey (WACHS), a population-based representative
      sample of 2,736 children aged 4 to 16 years (1,374 girls); and administrative
      data relating to all their subsequent births and hospital admissions. We used
      weighted population estimates to examine differences between rates for teenage
      pregnancy, motherhood and abortion. We used Cox proportional hazards regression
      to model risk for teenage pregnancy. RESULTS: There were 155 girls aged less than
      20 years at the time of their first recorded pregnancy. Teenage pregnancy was
      significantly associated with: family type; highest school year completed by
      primary carer; combined carer income; whether the primary carer was a smoker; and
      whether the girl herself displayed aggressive and delinquent behaviours. An age
      interaction analysis on the association with aggressive and delinquent behaviours
      found that while girls with aggressive and delinquent behaviours who were older
      at the time of the survey were at highest risk of teenage pregnancy, there was
      elevated risk for future teenage pregnancy across all ages. CONCLUSIONS: Our
      findings suggest that interventions to reduce teenage pregnancy rates could be
      introduced during primary school years, including those that are focused on the
      prevention and management of aggressive and delinquent behaviour.

PMID- 20149220
TI  - Transcriptional profiling of bovine intervertebral disc cells: implications for
      identification of normal and degenerate human intervertebral disc cell
      phenotypes.
AB  - INTRODUCTION: Nucleus pulposus (NP) cells have a phenotype similar to articular
      cartilage (AC) cells. However, the matrix of the NP is clearly different to that
      of AC suggesting that specific cell phenotypes exist. The aim of this study was
      to identify novel genes that could be used to distinguish bovine NP cells from AC
      and annulus fibrosus (AF) cells, and to further determine their expression in
      normal and degenerate human intervertebral disc (IVD) cells. METHODS: Microarrays
      were conducted on bovine AC, AF and NP cells, using Affymetrix Genechip(R) Bovine
      Genome Arrays. Differential expression levels for a number of genes were
      confirmed by quantitative real time polymerase chain reaction (qRT-PCR) on
      bovine, AC, AF and NP cells, as well as separated bovine NP and notochordal (NC)
      cells. Expression of these novel markers were further tested on normal human AC,
      AF and NP cells, and degenerate AF and NP cells. RESULTS: Microarray comparisons
      between NP/AC&AF and NP/AC identified 34 NP-specific and 49 IVD-specific genes
      respectively that were differentially expressed > or =100 fold. A subset of these
      were verified by qRT-PCR and shown to be expressed in bovine NC cells. Eleven
      genes (SNAP25, KRT8, KRT18, KRT19, CDH2, IBSP, VCAN, TNMD, BASP1, FOXF1 & FBLN1)
      were also differentially expressed in normal human NP cells, although to a lesser
      degree. Four genes (SNAP25, KRT8, KRT18 and CDH2) were significantly decreased in
      degenerate human NP cells, while three genes (VCAN, TNMD and BASP1) were
      significantly increased in degenerate human AF cells. The IVD negative marker
      FBLN1 was significantly increased in both degenerate human NP and AF cells.
      CONCLUSIONS: This study has identified a number of novel genes that characterise
      the bovine and human NP and IVD transcriptional profiles, and allows for
      discrimination between AC, AF and NP cells. Furthermore, the similarity in
      expression profiles of the separated NP and NC cell populations suggests that
      these two cell types may be derived from a common lineage. Although interspecies
      variation, together with changes with IVD degeneration were noted, use of this
      gene expression signature will benefit tissue engineering studies where defining
      the NP phenotype is paramount.

PMID- 20149222
TI  - Clinical validity of a population database definition of remission in patients
      with major depression.
AB  - BACKGROUND: Major depression (MD) is one of the most frequent diagnoses in
      Primary Care. It is a disabling illness that increases the use of health
      resources. AIM: To describe the concordance between remission according to
      clinical assessment and remission obtained from the computerized prescription
      databases of patients with MD in a Spanish population. METHODS:  DESIGN:
      multicenter cross-sectional. The population under study was comprised of people
      from six primary care facilities, who had a MD episode between January 2003 and
      March 2007. A specialist in psychiatry assessed a random sample of patient
      histories and determined whether a certain patient was in remission according to
      clinical criteria (ICPC-2). Regarding the databases, patients were considered in
      remission when they did not need further prescriptions of AD for at least 6
      months after completing treatment for a new episode. Validity indicators
      (sensitivity [S], specificity [Sp]) and clinical utility (positive and negative
      probability ratio [PPR] and [NPR]) were calculated. The concordance index was
      established using Cohen's kappa coefficient. Significance level was p < 0.05.
      RESULTS: 133 patient histories were reviewed. The kappa coefficient was 82.8%
      (confidence intervals [CI] were 95%: 73.1 - 92.6), PPR 9.8% and NPR 0.1%.
      Allocation discrepancies between both criteria were found in 11 patients. S was
      92.5% (CI was 95%: 88.0 - 96.9%) and Sp was 90.6% (CI was 95%: 85.6 - 95.6%), p <
      0.001. Reliability analysis: Cronbach's alpha: 90.6% (CI was 95%: 85.6 - 95.6%).
      CONCLUSIONS: Results show an acceptable level of concordance between remission
      obtained from the computerized databases and clinical criteria. The major
      discrepancies were found in diagnostic accuracy.

PMID- 20149223
TI  - Discovery and identification of a male-killing agent in the Japanese ladybird
      Propylea japonica (Coleoptera: Coccinellidae).
AB  - BACKGROUND: Endosymbionts that manipulate the reproduction of their hosts have
      been reported widely in invertebrates. One such group of endosymbionts is the
      male-killers. To date all male-killers reported are bacterial in nature, but
      comprise a diverse group. Ladybirds have been described as a model system for the
      study of male-killing, which has been reported in multiple species from
      widespread geographic locations. Whilst criteria of low egg hatch-rate and female
      biased progenic sex ratio have been used to identify female hosts of male
      killers, variation in vertical transmission efficiency and host genetic factors
      may result in variation in these phenotypic indicators of male-killer presence.
      Molecular identification of bacteria and screening for bacterial presence provide
      us with a more accurate method than breeding data alone to link the presence of
      the bacteria to the male-killing phenotype. In addition, by identifying the
      bacteria responsible we may find evidence for horizontal transfer between
      endosymbiont hosts and can gain insight into the evolutionary origins of male
      killing. Phylogenetic placement of male-killing bacteria will allow us to address
      the question of whether male-killing is a potential strategy for only some, or
      all, maternally inherited bacteria. Together, phenotypic and molecular
      characterisation of male-killers will allow a deeper insight into the
      interactions between host and endosymbiont, which ultimately may lead to an
      understanding of how male-killers identify and kill male-hosts. RESULTS: A male
      killer was detected in the Japanese coccinellid, Propylea japonica (Thunberg) a
      species not previously known to harbour male-killers. Families produced by female
      P. japonica showed significantly female-biased sex ratios. One female produced
      only daughters. This male-killer trait was maternally inherited and antibiotic
      treatment produced a full, heritable cure. Molecular analysis identified
      Rickettsia to be associated with the trait in this species of ladybird.
      CONCLUSION: We conclude that P. japonica is host to a bacterial male-killer that
      is vertically inherited with variable transmission efficiency. Rickettsia
      presence correlates with the male-killing trait, but there is some variation in
      the phenotypic expression of the trait due to interaction with host factors.
      Phylogenetic analysis using the 16S rRNA and 17 kDa antigen genes suggests there
      may have been horizontal transfer of Rickettsial male-killers between different
      ladybird hosts.

PMID- 20149224
TI  - High-density lipoproteins downregulate CCL2 production in human fibroblast-like
      synoviocytes stimulated by urate crystals.
AB  - INTRODUCTION: To investigate whether monosodium urate (MSU) crystals induce the
      production of CCL2 (monocyte chemoattractant protein-1; MCP-1) in human
      fibroblast-like synoviocytes (FLS) and whether this mechanism would be affected
      by high-density lipoproteins (HDL). METHODS: Human FLS isolated from synovial
      tissue explants were stimulated with MSU crystals (0.01 to 0.5 mg/ml) or
      interleukin (IL)-1beta (10 pg/ml) in the presence or absence of HDL (50 and 100
      microg/ml). The production and expression of CCL2 was evaluated with ELISA,
      confocal microscopy, immunofluorescence microscopy, chemotaxis assay, and real
      time quantitative PCR. RESULTS: Exposure of FLS to MSU crystals induced CCL2
      accumulation in culture medium in a dose- and time-dependent manner, reaching a
      plateau at 50 to 75 microg/ml MSU crystals and 20 to 24 hours. Although low, the
      induced CCL2 levels were sufficient to trigger mononuclear cell migration. In
      resting FLS, CCL2 was localized in small cytoplasmic vesicles whose number
      diminished with MSU crystal stimulation. Concomitantly, MSU crystals triggered
      the induction of CCL2 mRNA expression. All these processes were inhibited by HDL,
      which cause a 50% decrease in CCL2 mRNA levels and a dose-dependent inhibition of
      the release of CCL2. Similar results were obtained when FLS were pretreated with
      HDL and washed before activation by MSU crystals or IL-1beta, suggesting a direct
      effect of HDL on the FLS activation state. CONCLUSIONS: The present results
      demonstrate that MSU crystals induce FLS to release CCL2 that is stored in
      vesicles in resting conditions. This mechanism is inhibited by HDL, which may
      limit the inflammatory process by diminishing CCL2 production and, in turn,
      monocytes/macrophages recruitment in joints. This study confirms the
      antiinflammatory functions of HDL, which might play a part in the limitation of
      acute gout attack.

PMID- 20149225
TI  - Leptin receptor (LEPR) SNP polymorphisms in HELLP syndrome patients determined by
      quantitative real-time PCR and melting curve analysis.
AB  - BACKGROUND: Several studies have shown overexpression of leptin in microarray
      experiments in pre-eclampsia (PE) and in hemolysis, elevated liver enzymes, low
      platelets (HELLP) syndrome. We decided to study four leptin receptor (LEPR) SNP
      polymorphisms in HELLP syndrome patients by using quantitative real-time PCR and
      melting curve analysis. METHODS: DNA was isolated from blood samples from 83
      normotensive pregnant women and 75 HELLP syndrome patients. Four SNPs, LEPR
      c.326A>G (K109), LEPR c.668A>G (Q223R), LEPR c.1968G>C (K656N) and LEPR c.3024A>G
      (S1008) were determined by quantitative real-time PCR and melting curve analysis.
      Investigators were blinded to clinical outcomes. RESULTS: LEPR c.326A>G, LEPR
      c.668A>G, LEPR c.1968G>C and LEPR c.3024A>G allele, genotype and haplotype
      polymorphisms were not different in HELLP syndrome patients and normotensive
      healthy pregnants. There were strong linkage disequilibrium (LD) between loci
      c.326A>G and c.6687A>G (D' = 0.974), and c.668A>G and c.1968G>C (D' = 0.934), and
      c.326A>G and c.1968G>C (D' = 0.885), and c.1968G>C and c.3024A>G (D' = 1.0).
      However, linkages of c.3024A>G with c.668A>G (D' = 0.111) and c.326A>G (D' =
      0.398) were weak. The Hardy-Weinberg equilibrium was observed for all
      polymorphisms. However the LEPR c.326A>G AG genotype was twice more frequent and
      the (AG AG GG AG) haplotype was three times more frequent in HELLP syndrome
      patients. The introduced quantitative real-time PCR combined with melting curve
      analysis is a fast and reliable method for the determination of LEPR SNPs.
      CONCLUSION: Although certain LEPR haplotypes are more frequent in HELLP syndrome,
      we conclude that there is no compelling evidence that the four studied LEPR SNP
      polymorphisms associated with the development of HELLP syndrome.

PMID- 20149226
TI  - U12 type introns were lost at multiple occasions during evolution.
AB  - BACKGROUND: Two categories of introns are known, a common U2 type and a rare U12
      type. These two types of introns are removed by distinct spliceosomes. The
      phylogenetic distribution of spliceosomal RNAs that are characteristic of the U12
      spliceosome, i.e. the U11, U12, U4atac and U6atac RNAs, suggest that U12
      spliceosomes were lost in many phylogenetic groups. We have now examined the
      distribution of U2 and U12 introns in many of these groups. RESULTS: U2 and U12
      introns were predicted by making use of available EST and genomic sequences. The
      results show that in species or branches where U12 spliceosomal components are
      missing, also U12 type of introns are lacking. Examples are the choanoflagellate
      Monosiga brevicollis, Entamoeba histolytica, green algae, diatoms, and the fungal
      lineage Basidiomycota. Furthermore, whereas U12 splicing does not occur in
      Caenorhabditis elegans, U12 introns as well as U12 snRNAs are present in
      Trichinella spiralis, which is deeply branching in the nematode tree. A
      comparison of homologous genes in T. spiralis and C. elegans revealed different
      mechanisms whereby U12 introns were lost. CONCLUSIONS: The phylogenetic
      distribution of U12 introns and spliceosomal RNAs give further support to an
      early origin of U12 dependent splicing. In addition, this distribution identifies
      a large number of instances during eukaryotic evolution where such splicing was
      lost.

PMID- 20149228
TI  - Iron and ferritin accumulate in separate cellular locations in Phaseolus seeds.
AB  - BACKGROUND: Iron is an important micronutrient for all living organisms. Almost
      25% of the world population is affected by iron deficiency, a leading cause of
      anemia. In plants, iron deficiency leads to chlorosis and reduced yield. Both
      animals and plants may suffer from iron deficiency when their diet or environment
      lacks bioavailable iron. A sustainable way to reduce iron malnutrition in humans
      is to develop staple crops with increased content of bioavailable iron. Knowledge
      of where and how iron accumulates in seeds of crop plants will increase the
      understanding of plant iron metabolism and will assist in the production of
      staples with increased bioavailable iron. RESULTS: Here we reveal the
      distribution of iron in seeds of three Phaseolus species including thirteen
      genotypes of P. vulgaris, P. coccineus, and P. lunatus. We showed that high
      concentrations of iron accumulate in cells surrounding the provascular tissue of
      P. vulgaris and P. coccineus seeds. Using the Perls' Prussian blue method, we
      were able to detect iron in the cytoplasm of epidermal cells, cells near the
      epidermis, and cells surrounding the provascular tissue. In contrast, the protein
      ferritin that has been suggested as the major iron storage protein in legumes was
      only detected in the amyloplasts of the seed embryo. Using the non-destructive
      micro-PIXE (Particle Induced X-ray Emission) technique we show that the tissue in
      the proximity of the provascular bundles holds up to 500 microg g(-1) of iron,
      depending on the genotype. In contrast to P. vulgaris and P. coccineus, we did
      not observe iron accumulation in the cells surrounding the provascular tissues of
      P. lunatus cotyledons. A novel iron-rich genotype, NUA35, with a high
      concentration of iron both in the seed coat and cotyledons was bred from a cross
      between an Andean and a Mesoamerican genotype. CONCLUSIONS: The presented results
      emphasize the importance of complementing research in model organisms with
      analysis in crop plants and they suggest that iron distribution criteria should
      be integrated into selection strategies for bean biofortification.

PMID- 20149227
TI  - The zebrafish genome encodes the largest vertebrate repertoire of functional
      aquaporins with dual paralogy and substrate specificities similar to mammals.
AB  - BACKGROUND: Aquaporins are integral membrane proteins that facilitate the
      transport of water and small solutes across cell membranes. These proteins are
      vital for maintaining water homeostasis in living organisms. In mammals, thirteen
      aquaporins (AQP0-12) have been characterized, but in lower vertebrates, such as
      fish, the diversity, structure and substrate specificity of these membrane
      channel proteins are largely unknown. RESULTS: The screening and isolation of
      transcripts from the zebrafish (Danio rerio) genome revealed eighteen sequences
      structurally related to the four subfamilies of tetrapod aquaporins, i.e.,
      aquaporins (AQP0, -1 and -4), water and glycerol transporters or
      aquaglyceroporins (Glps; AQP3 and AQP7-10), a water and urea transporter (AQP8),
      and two unorthodox aquaporins (AQP11 and -12). Phylogenetic analyses of
      nucleotide and deduced amino acid sequences demonstrated dual paralogy between
      teleost and human aquaporins. Three of the duplicated zebrafish isoforms have
      unlinked loci, two have linked loci, while DrAqp8 was found in triplicate across
      two chromosomes. Genomic sequencing, structural analysis, and maximum likelihood
      reconstruction, further revealed the presence of a putative pseudogene that
      displays hybrid exons similar to tetrapod AQP5 and -1. Ectopic expression of the
      cloned transcripts in Xenopus laevis oocytes demonstrated that zebrafish
      aquaporins and Glps transport water or water, glycerol and urea, respectively,
      whereas DrAqp11b and -12 were not functional in oocytes. Contrary to humans and
      some rodents, intrachromosomal duplicates of zebrafish AQP8 were water and urea
      permeable, while the genomic duplicate only transported water. All aquaporin
      transcripts were expressed in adult tissues and found to have divergent
      expression patterns. In some tissues, however, redundant expression of
      transcripts encoding two duplicated paralogs seems to occur. CONCLUSION: The
      zebrafish genome encodes the largest repertoire of functional vertebrate
      aquaporins with dual paralogy to human isoforms. Our data reveal an early and
      specific diversification of these integral membrane proteins at the root of the
      crown-clade of Teleostei. Despite the increase in gene copy number, zebrafish
      aquaporins mostly retain the substrate specificity characteristic of the tetrapod
      counterparts. Based upon the integration of phylogenetic, genomic and functional
      data we propose a new classification for the piscine aquaporin superfamily.

PMID- 20149229
TI  - A mouse model for the Sezary syndrome.
AB  - BACKGROUND: The Sezary syndrome is an aggressive leukemic form of cutaneous T
      cell lymphoma and there is no cure of this disease. Until now there is no true
      animal model for Sezary syndrome, by which new drugs against the disease could be
      tested. METHODS: Immune deficient CB-17 SCID beige mice were injected
      subcutaneously with HUT78 cells, a cell line, derived from a Sezary syndrome
      patient. Developing tumors were analyzed by immunohistochemistry. RESULTS:
      Injected HUT78 cells formed tumors at the site of injection. In contrast to the
      Sezary syndrome in man, no malignant cells were observed in the blood of tumor
      bearing CB-17 SCID beige mice. The tumors appeared 44-62 days after injection and
      tumor bearing mice survived further 25 - 62 days until they had to be euthanized
      according to the guidelines of the Swiss animal protection law, since the tumors
      had reached the maximal allowed size. CONCLUSION: Although the mouse model does
      not exactly match the human disease, it will be suited for tests of new
      substances for the treatment of the Sezary syndrome. The formation of an isolated
      tumor on the skin has the advantage that the effect of a potential drug can be
      directly monitored without the use of invasive methods.

PMID- 20149230
TI  - Understanding human functioning using graphical models.
AB  - BACKGROUND: Functioning and disability are universal human experiences. However,
      our current understanding of functioning from a comprehensive perspective is
      limited. The development of the International Classification of Functioning,
      Disability and Health (ICF) on the one hand and recent developments in graphical
      modeling on the other hand might be combined and open the door to a more
      comprehensive understanding of human functioning. The objective of our paper
      therefore is to explore how graphical models can be used in the study of ICF data
      for a range of applications. METHODS: We show the applicability of graphical
      models on ICF data for different tasks: Visualization of the dependence structure
      of the data set, dimension reduction and comparison of subpopulations. Moreover,
      we further developed and applied recent findings in causal inference using
      graphical models to estimate bounds on intervention effects in an observational
      study with many variables and without knowing the underlying causal structure.
      RESULTS: In each field, graphical models could be applied giving results of high
      face-validity. In particular, graphical models could be used for visualization of
      functioning in patients with spinal cord injury. The resulting graph consisted of
      several connected components which can be used for dimension reduction. Moreover,
      we found that the differences in the dependence structures between subpopulations
      were relevant and could be systematically analyzed using graphical models.
      Finally, when estimating bounds on causal effects of ICF categories on general
      health perceptions among patients with chronic health conditions, we found that
      the five ICF categories that showed the strongest effect were plausible.
      CONCLUSIONS: Graphical Models are a flexible tool and lend themselves for a wide
      range of applications. In particular, studies involving ICF data seem to be
      suited for analysis using graphical models.

PMID- 20149231
TI  - Cerebral net exchange of large neutral amino acids after lipopolysaccharide
      infusion in healthy humans.
AB  - INTRODUCTION: Alterations in circulating large neutral amino acids (LNAAs),
      leading to a decrease in the plasma ratio between branched-chain and aromatic
      amino acids (BCAA/AAA ratio), may be involved in sepsis-associated
      encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs
      along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human
      experimental model of systemic inflammation. METHODS: The BCAA/AAA ratio, the
      cerebral delivery, and net exchange of LNAAs and ammonia were measured before and
      1 hour after a 4-hour intravenous infusion of Escherichia coli lipopolysaccharide
      (LPS) in 12 healthy young men. RESULTS: LPS induced systemic inflammation,
      reduced the BCAA/AAA ratio, increased the cerebral delivery and unidirectional
      influx of phenylalanine, and abolished the net cerebral influx of the BCAAs
      leucine and isoleucine. Furthermore, a net cerebral efflux of glutamine, which
      was independent of the cerebral net exchange of ammonia, was present after LPS
      infusion. CONCLUSIONS: Systemic inflammation may affect brain function by
      reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

PMID- 20149232
TI  - Pp65 antigenemia, plasma real-time PCR and DBS test in symptomatic and
      asymptomatic cytomegalovirus congenitally infected newborns.
AB  - BACKGROUND: Many congenitally cytomegalovirus-infected (cCMV) neonates are at
      risk for severe consequences, even if they are asymptomatic at birth. The
      assessment of the viral load in neonatal blood could help in identifying the
      babies at risk of sequelae. METHODS: In the present study, we elaborated the
      results obtained on blood samples collected in the first two weeks of life from
      22 symptomatic and 48 asymptomatic newborns with cCMV diagnosed through urine
      testing. We evaluated the performances of two quantitative methods (pp65
      antigenemia test and plasma Real-time PCR) and the semi-quantitative results of
      dried blood sample (DBS) test in the aim of identifying a valid method for
      measuring viral load. RESULTS: Plasma qPCR and DBS tests were positive in 100% of
      cases, antigenemia in 81%. Only the latter test gave quantitatively different
      results in symptomatic versus asymptomatic children. qPCR values of 103 copies/ml
      were found in 52% of newborn. "Strong" DBS test positivity cases had higher
      median values of both pp65 positive PBL and DNA copies/ml than cases with a
      "weak" positivity. CONCLUSIONS: As expected antigenemia test was less sensitive
      than molecular tests and DBS test performed better on samples with higher rates
      of pp65 positive PBL and higher numbers of DNA copies/ml. The prognostic
      significance of the results of these tests will be evaluated on completion of the
      ongoing collection of follow-up data of these children.

PMID- 20149233
TI  - LINNAEUS: a species name identification system for biomedical literature.
AB  - BACKGROUND: The task of recognizing and identifying species names in biomedical
      literature has recently been regarded as critical for a number of applications in
      text and data mining, including gene name recognition, species-specific document
      retrieval, and semantic enrichment of biomedical articles. RESULTS: In this paper
      we describe an open-source species name recognition and normalization software
      system, LINNAEUS, and evaluate its performance relative to several automatically
      generated biomedical corpora, as well as a novel corpus of full-text documents
      manually annotated for species mentions. LINNAEUS uses a dictionary-based
      approach (implemented as an efficient deterministic finite-state automaton) to
      identify species names and a set of heuristics to resolve ambiguous mentions.
      When compared against our manually annotated corpus, LINNAEUS performs with 94%
      recall and 97% precision at the mention level, and 98% recall and 90% precision
      at the document level. Our system successfully solves the problem of
      disambiguating uncertain species mentions, with 97% of all mentions in PubMed
      Central full-text documents resolved to unambiguous NCBI taxonomy identifiers.
      CONCLUSIONS: LINNAEUS is an open source, stand-alone software system capable of
      recognizing and normalizing species name mentions with speed and accuracy, and
      can therefore be integrated into a range of bioinformatics and text-mining
      applications. The software and manually annotated corpus can be downloaded freely
      at http://linnaeus.sourceforge.net/.

PMID- 20149234
TI  - Elucidation of the outer membrane proteome of Salmonella enterica serovar
      Typhimurium utilising a lipid-based protein immobilization technique.
AB  - BACKGROUND: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major
      cause of human gastroenteritis worldwide. The outer membrane proteins expressed
      by S. Typhimurium mediate the process of adhesion and internalisation within the
      intestinal epithelium of the host thus influencing the progression of disease.
      Since the outer membrane proteins are surface-exposed, they provide attractive
      targets for the development of improved antimicrobial agents and vaccines.
      Various techniques have been developed for their characterisation, but issues
      such as carryover of cytosolic proteins still remain a problem. In this study we
      attempted to characterise the surface proteome of S. Typhimurium using Lipid
      based Protein Immobilisation technology in the form of LPI FlowCells. No
      detergents are required and no sample clean up is needed prior to downstream
      analysis. The immobilised proteins can be digested with proteases in multiple
      steps to increase sequence coverage, and the peptides eluted can be characterised
      directly by liquid chromatography - tandem mass spectrometry (LC-MS/MS) and
      identified from mass spectral database searches. RESULTS: In this study, 54 outer
      membrane proteins, were identified with two or more peptide hits using a multi
      step digest approach. Out of these 28 were lipoproteins, nine were involved in
      transport and three with enzyme activity These included the transporters BtuB
      which is responsible for the uptake of vitamin B12, LamB which is involved in the
      uptake of maltose and maltodextrins and LolB which is involved in the
      incorporation of lipoproteins in the outer membrane. Other proteins identified
      included the enzymes MltC which may play a role in cell elongation and division
      and NlpD which is involved in catabolic processes in cell wall formation as well
      as proteins involved in virulence such as Lpp1, Lpp2 and OmpX. CONCLUSION: Using
      a multi-step digest approach the LPI technique enables the incorporation of a
      multi-step protease work flow ensuring enough sequence coverage of membrane
      proteins subsequently leading to the identification of more membrane proteins
      with higher confidence. Compared to current sub-cellular fractionation procedures
      and previous published work, the LPI technique currently provides the widest
      coverage of outer membrane proteins identified as demonstrated here for
      Salmonella Typhimurium.

PMID- 20149235
TI  - Adherence to and acceptability of artemether-lumefantrine as first-line anti
      malarial treatment: evidence from a rural community in Tanzania.
AB  - BACKGROUND: Controlled clinical trials have shown that a six-dose regimen of
      artemether-lumefantrine (AL) therapy for uncomplicated Plasmodium falciparum
      malaria results in cure rates >95% with good tolerability. MATERIALS AND METHODS:
      A prospective study was carried out to document the adherence to and
      acceptability of AL administration. This was undertaken in the context of the
      ALIVE study, a prospective, community-based, observational study in a rural,
      malaria-endemic area of Tanzania. Following microscopic confirmation of P.
      falciparum infection, the first AL dose was taken under supervision, with the
      subsequent five doses taken unsupervised at home. Patients were randomized to
      receive a home-based assessment close to the scheduled time for one of the
      unsupervised doses, but were blinded to which follow-up visit they had been
      allocated. A structured questionnaire was administered by trained staff and AL
      consumption was confirmed by inspection of blister packs. RESULTS: A total of 552
      patients were recruited of whom 352 (63.8%) were <13 years old. The randomization
      process allocated 112, 109, 110, 100 and 111 patients to a follow-up visit after
      doses 2, 3, 4, 5 and 6, respectively. For dose 2, 92.0% of patients (103/112)
      correctly took AL at 8 +/- 1 hours after dose 1. The remaining doses were taken
      within four hours of the correct time in 87-95% of cases. Nine patients (1.7%)
      missed one dose. Blister packs were available for inspection in 548 of cases
      (99.3%) and confirmed patient-reported data that the previous dose had been
      administered. Nearly all patients took AL with water (549/552 [99.5%]). Two
      patients (0.4%) took the drug with food. The dosing pictogram and clustering of
      tablets within the blister packs was considered helpful by 91.8% and 100.0% of
      patients, respectively. Overall, 87.1% of patients (481/552) found AL easier to
      take/administer than sulphadoxine-pyrimethamine (SP) and 87.7% (484/552) believed
      that AL was more effective than SP. DISCUSSION: Factors contributing to adherence
      were likely to be helpful packaging, pictorial dosing instructions and patients'
      conviction that AL is effective. CONCLUSION: Adherence to the dosing regimen and
      timing of AL administration was very good.

PMID- 20149236
TI  - Health beliefs before and after participation on an exercised-based
      rehabilitation programme for chronic knee pain: doing is believing.
AB  - BACKGROUND: To explore the health beliefs, experiences, treatment and
      expectations of people with chronic knee pain, and investigate if, how and why
      these change after taking part on an integrated exercise-based rehabilitation
      programme--Enabling Self-management and Coping with Arthritis knee Pain through
      Exercise, ESCAPE-knee pain. METHODS: Semi-structured interviews were conducted
      with people with chronic knee pain, before (n=29) and after (n=23) participation
      on the programme. Thematic analysis was used to document people's baseline health
      beliefs, attitudes and cognitions, and to see if how and why these changed after
      completing the programme. RESULTS: Initially people had poor understanding and
      negative, fatalistic beliefs about the management or prognosis for knee pain.
      Following the programme the majority of participants had positive experiences
      describing improvement in pain, physical and psychosocial functioning, greater
      knowledge and understanding of their condition and treatment options, and in
      their ability to use exercise to control symptoms. Beliefs about the causation
      and prognosis of knee pain were unchanged, but their concerns about possible
      dangers of exercise had decreased, they appreciated how exercise could reduce
      symptoms (treatment beliefs) and their confidence in their ability to use
      exercise to effect improvements (exercise self-efficacy) increased. These
      improvements were attributed to the content and structure of the programme, and
      the care and guidance of the physiotherapist. Several expressed a need for on
      going support. CONCLUSIONS: ESCAPE-knee pain appears to achieve improvements by
      increasing people's treatment belief in safety and the utility of exercise to
      control symptoms, rather than alteration in their beliefs about causation or
      prognosis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN94658828.

PMID- 20149237
TI  - Kypho-IORT--a novel approach of intraoperative radiotherapy during kyphoplasty
      for vertebral metastases.
AB  - BACKGROUND: Instable and painful vertebral metastases in patients with
      progressive visceral metastases present a common therapeutic dilemma. We
      developed a novel approach to deliver intraoperative radiotherapy (IORT) during
      kyphoplasty and report the first treated case. METHODS/RESULTS: 60 year old
      patient with metastasizing breast cancer under chemotherapy presented with a
      newly diagnosed painful metastasis in the 12th thoracic vertebra. Under general
      anaesthesia, a bipedicular approach into the vertebra was chosen with insertion
      of specially designed metallic sleeves to guide the electron drift tube of the
      miniature X-ray generator (INTRABEAM, Carl Zeiss Surgical, Oberkochen, Germany).
      This was inserted with a novel sheet designed for this approach protecting the
      drift tube. A radiation dose of 8 Gy in 5 mm distance (50 kV X-rays) was
      delivered. The kyphoplasty balloons (KyphX, Kyphon Inc, Sunnyvale) were inflated
      after IORT and polymethylmethacrylate cement was injected. The whole procedure
      lasted less than 90 minutes. CONCLUSION: In conclusion, this novel, minimally
      invasive procedure can be performed in standard operating rooms and may become a
      valuable option for patients with vertebral metastases providing immediate
      stability and local control. A phase I/II study is under way to establish the
      optimal dose prescription.

PMID- 20149238
TI  - Multilevel analysis of covariation in socioeconomic predictors of physical
      functioning and psychological well-being among older people in rural Vietnam.
AB  - BACKGROUND: There remains a lack of research on co-variation of multiple health
      outcomes and their socio-economic co-patterning, especially among the elderly.
      This papers aims to 1) examine the effects of different socio-economic factors on
      physical functioning and psychological well-being among older adults in a rural
      community in northern Vietnam; and 2) investigate the extent to which the two
      outcomes variables co-vary within individuals. METHODS: We analyzed the data from
      the WHO/INDEPTH study on global ageing and adult health conducted on 8535 people
      aged 50 years old and over in Bavi district of Vietnam in 2006. A multivariate
      response model was constructed to answer our research questions. The model treats
      the individual as a level two unit and the multiple measurements observed within
      an individual as a level one unit. RESULTS: Lower physical functioning and
      psychological well-being were found in 1) women; 2) older people; 3) people with
      lower education level; 4) people who were currently single; 5) respondents from
      poorer household; and 6) mountainous dwellers compared to that in those of other
      category(ies) of the same variable. Socioeconomic factors accounted for about 24%
      and 7% of variation in physical functioning and psychological well-being scores,
      respectively. The adjusted correlation coefficient (0.35) indicates that physical
      functioning and psychological well-being did not strongly co-vary. CONCLUSIONS:
      The present study shows that there exist problems of inequality in health among
      older adults in the study setting. This finding highlights the importance of
      analyzing multiple dimensions of health status simultaneously in inequality
      investigations.

PMID- 20149239
TI  - Flow cytometry for the evaluation of anti-plasmodial activity of drugs on
      Plasmodium falciparum gametocytes.
AB  - BACKGROUND: The activity of promising anti-malarial drugs against Plasmodium
      gametocytes is hard to evaluate even in vitro. This is because visual examination
      of stained smears, which is commonly used, is not totally convenient. In the
      current study, flow cytometry has been used to study the effect of established
      anti-malarial drugs against sexual stages obtained from W2 strain of Plasmodium
      falciparum. Gametocytes were treated for 48 h with different drug concentrations
      and the gametocytaemia was then determined by flow cytometry and compared with
      visual estimation by microscopy. RESULTS AND CONCLUSIONS: Initially
      gametocytaemia was evaluated either using light microscopy or flow cytometry. A
      direct correlation (r2 = 0.9986) was obtained. Two distinct peaks were observed
      on cytometry histograms and were attributed to gametocyte populations. The
      activities of established anti-malarial compounds were then measured by flow
      cytometry and the results were equivalent to those obtained using light
      microscopy. Primaquine and artemisinin had IC50 of 17.6 microM and 1.0 microM,
      respectively. Gametocyte sex was apparently distinguishable by flow cytometry as
      evaluated after induction of exflagellation by xanthurenic acid. These data form
      the basis of further studies for developing new methods in drug discovery to
      decrease malaria transmission.

PMID- 20149240
TI  - NSC114792, a novel small molecule identified through structure-based
      computational database screening, selectively inhibits JAK3.
AB  - BACKGROUND: Human or animals lacking either JAK3 or the common gamma chain
      (gammac) expression display severe combined immunodeficiency disease, indicating
      the crucial role of JAK3 in T-cell development and the homeostasis of the immune
      system. JAK3 has also been suggested to contribute to the pathogenesis of
      tumorigenesis. Recent studies identified activating JAK3 mutations in patients
      with various hematopoietic malignancies, including acute megakaryoblastic
      leukemia. Importantly, functional analyses of some of those JAK3 mutations have
      been shown to cause lethal hematopoietic malignancies in animal models. These
      observations make JAK3 an ideal therapeutic target for the treatment of various
      human diseases. To identify novel small molecule inhibitors of JAK3, we performed
      structure-based virtual screen using the 3D structure of JAK3 kinase domain and
      the NCI diversity set of compounds. RESULTS: We identified NSC114792 as a lead
      compound. This compound directly blocked the catalytic activity of JAK3 but not
      that of other JAK family members in vitro. In addition, treatment of 32D/IL
      2Rbeta cells with the compound led to a block in IL-2-dependent activation of
      JAK3/STAT5 but not IL-3-dependent activation of JAK2/STAT5. Consistent with the
      specificity of NSC114792 for JAK3, it selectively inhibited persistently
      activated JAK3, but failed to affect the activity of other JAK family members and
      other oncogenic kinases in various cancer cell lines. Finally, we showed that
      NSC114792 decreases cell viability by inducing apoptosis through down-regulating
      anti-apoptotic gene expression only in cancer cells harboring persistently-active
      JAK3. CONCLUSIONS: NSC114792 is a lead compound that selectively inhibits JAK3
      activity. Therefore, our study suggests that this small molecule inhibitor of
      JAK3 can be used as a starting point to develop a new class of drugs targeting
      JAK3 activity, and may have therapeutic potential in various diseases that are
      caused by aberrant JAK3 activity.

PMID- 20149241
TI  - Mapping main, epistatic and sex-specific QTL for body composition in a chicken
      population divergently selected for low or high growth rate.
AB  - BACKGROUND: Delineating the genetic basis of body composition is important to
      agriculture and medicine. In addition, the incorporation of gene-gene
      interactions in the statistical model provides further insight into the genetic
      factors that underlie body composition traits. We used Bayesian model selection
      to comprehensively map main, epistatic and sex-specific QTL in an F2 reciprocal
      intercross between two chicken lines divergently selected for high or low growth
      rate. RESULTS: We identified 17 QTL with main effects across 13 chromosomes and
      several sex-specific and sex-antagonistic QTL for breast meat yield, thigh +
      drumstick yield and abdominal fatness. Different sets of QTL were found for both
      breast muscles [Pectoralis (P) major and P. minor], which suggests that they
      could be controlled by different regulatory mechanisms. Significant interactions
      of QTL by sex allowed detection of sex-specific and sex-antagonistic QTL for body
      composition and abdominal fat. We found several female-specific P. major QTL and
      sex-antagonistic P. minor and abdominal fatness QTL. Also, several QTL on
      different chromosomes interact with each other to affect body composition and
      abdominal fatness. CONCLUSIONS: The detection of main effects, epistasis and sex
      dimorphic QTL suggest complex genetic regulation of somatic growth. An
      understanding of such regulatory mechanisms is key to mapping specific genes that
      underlie QTL controlling somatic growth in an avian model.

PMID- 20149242
TI  - Oestradiol-17beta plasma concentrations after intramuscular injection of
      oestradiol benzoate or oestradiol cypionate in llamas (Lama glama).
AB  - BACKGROUND: Llamas (Lama glama) are induced ovulators and the process of
      ovulation depends on dominant follicular size. In addition, a close relationship
      between behavioural estrus and ovulation is not registered in llamas. Therefore,
      the exogenous control of follicular development with hormones aims to predict the
      optimal time to mate. Oestradiol-17beta (E2) and its esters are currently used in
      domestic species, including camelids, in synchronization treatments. But, in
      llamas, there is no reports regarding the appropriate dosages to be used and most
      protocols have been designed by extrapolation from those recommended for other
      ruminants. The aim of the present study was to characterize plasma E2
      concentrations in intact female llamas following a single intramuscular (i.m.)
      injection of two oestradiol esters: oestradiol benzoate (EB) and oestradiol
      cypionate (ECP). METHODS: Twelve non pregnant and non lactating sexually mature
      llamas were i.m. injected on day 0 with 2.5 mg of EB (EB group, n = 6) or ECP
      (ECP group, n = 6). Blood samples were collected immediately before injection, at
      1, 6, 12, 24 h after treatment and then daily until day 14 post injection.
      Changes in hormone concentrations with time were analyzed in each group by
      analysis of variance (ANOVA) using a repeated measures (within-SS) design. Plasma
      E2 concentrations and area under the concentration-time curve (AUC) values were
      compared between groups by ANOVA. In all cases a Least-Significant Difference
      test (LSD) was used to determine differences between means. Hormonal and AUC data
      are expressed as mean +/- S.E.M. RESULTS: Peak plasma E2 concentrations were
      achieved earlier and were higher in EB group than in ECP group. Thereafter, E2
      returned to physiological concentrations earlier in EB group (day 5) than in ECP
      group (day 9). Although plasma E2 profiles differed over time among groups there
      were no differences between them on AUC values. CONCLUSIONS: The i.m. injection
      of a single dose of both oestradiol esters resulted in plasma E2 concentrations
      exceeding physiological values for a variable period. Moreover, the plasma E2
      profiles observed depended on the derivative of oestradiol administered. This
      basic information becomes relevant at defining treatment protocols including
      oestrogens in llamas.

PMID- 20149243
TI  - Identification of genes involved in the mutualistic colonization of the nematode
      Heterorhabditis bacteriophora by the bacterium Photorhabdus luminescens.
AB  - BACKGROUND: Photorhabdus are Gram negative entomopathogenic bacteria that also
      have a mutualistic association with nematodes from the family Heterorhabditis. An
      essential part of this symbiosis is the ability of the bacterium to colonize the
      gut of the freeliving form of the nematode called the infective juvenile (IJ).
      Although the colonization process (also called transmission) has been described
      phenomonologically very little is known about the underlying molecular
      mechanisms. Therefore, in this study, we were interested in identifying genes in
      Photorhabdus that are important for IJ colonization. RESULTS: In this work we
      genetically tagged P. luminescens TT01 with gfp and constructed a library
      containing over 3200 mutants using the suicide vector, pUT-Km2. Using a
      combination of in vitro symbiosis assays and fluorescent microscopy we screened
      this library for mutants that were affected in their ability to colonize the IJ
      i.e. with decreased transmission frequencies. In total 8 mutants were identified
      with transmission frequencies of <o= 30% compared to wild-type. These mutants
      were mapped to 6 different genetic loci; the pbgPE operon, galE, galU, proQ, asmA
      and hdfR. The pbgPE, galE and galU mutants were all predicted to be involved in
      LPS biosynthesis and, in support of this, we have shown that these mutants are
      avirulent and sensitive to the cationic antimicriobial peptide, polymyxin B. On
      the other hand the proQ, asmA and hdfR mutants were not affected in virulence and
      were either as resistant (proQ) or slightly more sensitive (asmA, hdfR) to
      polymyxin B than the wild-type (WT). CONCLUSIONS: This is the first report
      describing the outcome of a comprehensive screen looking for transmission mutants
      in Photorhabdus. In total 6 genetic loci were identified and we present evidence
      that all of these loci are involved in the assembly and/or maintenance of LPS and
      other factors associated with the cell surface. Interestingly several, but not
      all, of the transmission mutants identified were also avirulent suggesting that
      there is a significant, but not complete, genetic overlap between pathogenicity
      and mutualism. Therefore, this study highlights the importance of the cell
      surface in mediating the symbiotic and pathogenic interactions of Photorhabdus.

PMID- 20149244
TI  - Overground walking speed changes when subjected to body weight support conditions
      for nonimpaired and post stroke individuals.
AB  - BACKGROUND: Previous research has shown that body weight support (BWS) has the
      potential to improve gait speed for individuals post-stroke. However, body weight
      support also reduces the optimal walking speed at which energy use is minimized
      over the gait cycle indicating that BWS should reduce walking speed capability.
      METHODS: Nonimpaired subjects and subjects post-stroke walked at a self-selected
      speed over a 15 m walkway. Body weight support (BWS) was provided to subjects at
      0%, 10%, 20%, 30%, and 40% of the subject's weight while they walked overground
      using a robotic body weight support system. Gait speed, cadence, and average step
      length were calculated for each subject using recorded data on their time to walk
      10 m and the number of steps taken. RESULTS: When subjected to greater levels of
      BWS, self-selected walking speed decreased for the nonimpaired subjects. However,
      subjects post-stroke showed an average increase of 17% in self-selected walking
      speed when subjected to some level of BWS compared to the 0% BWS condition. Most
      subjects showed this increase at the 10% BWS level. Gait speed increases
      corresponded to an increase in step length, but not cadence. CONCLUSIONS: The BWS
      training environment results in decreased self-selected walking speed in
      nonimpaired individuals, however self-selected overground walking speed is
      facilitated when provided with a small percentage of body weight support for
      people post-stroke.

PMID- 20149245
TI  - Positive selection neighboring functionally essential sites and disease
      implicated regions of mammalian reproductive proteins.
AB  - BACKGROUND: Reproductive proteins are central to the continuation of all
      mammalian species. The evolution of these proteins has been greatly influenced by
      environmental pressures induced by pathogens, rival sperm, sexual selection and
      sexual conflict. Positive selection has been demonstrated in many of these
      proteins with particular focus on primate lineages. However, the mammalia are a
      diverse group in terms of mating habits, population sizes and germ line
      generation times. We have examined the selective pressures at work on a number of
      novel reproductive proteins across a wide variety of mammalia. RESULTS: We show
      that selective pressures on reproductive proteins are highly varied. Of the 10
      genes analyzed in detail, all contain signatures of positive selection either
      across specific sites or in specific lineages or a combination of both. Our
      analysis of SP56 and Col1a1 are entirely novel and the results show positively
      selected sites present in each gene. Our findings for the Col1a1 gene are
      suggestive of a link between positive selection and severe disease type. We find
      evidence in our dataset to suggest that interacting proteins are evolving in
      symphony: most likely to maintain interacting functionality. CONCLUSION: Our in
      silico analyses show positively selected sites are occurring near catalytically
      important regions suggesting selective pressure to maximize efficient
      fertilization. In those cases where a mechanism of protein function is not fully
      understood, the sites presented here represent ideal candidates for mutational
      study. This work has highlighted the widespread rate heterogeneity in mutational
      rates across the mammalia and specifically has shown that the evolution of
      reproductive proteins is highly varied depending on the species and interacting
      partners. We have shown that positive selection and disease are closely linked in
      the Col1a1 gene.

PMID- 20149246
TI  - Retail sector distribution chains for malaria treatment in the developing world:
      a review of the literature.
AB  - BACKGROUND: In many low-income countries, the retail sector plays an important
      role in the treatment of malaria and is increasingly being considered as a
      channel for improving medicine availability. Retailers are the last link in a
      distribution chain and their supply sources are likely to have an important
      influence on the availability, quality and price of malaria treatment. This
      article presents the findings of a systematic literature review on the retail
      sector distribution chain for malaria treatment in low and middle-income
      countries. METHODS: Publication databases were searched using key terms relevant
      to the distribution chain serving all types of anti-malarial retailers.
      Organizations involved in malaria treatment and distribution chain related
      activities were contacted to identify unpublished studies. RESULTS: A total of 32
      references distributed across 12 developing countries were identified. The
      distribution chain had a pyramid shape with numerous suppliers at the bottom and
      fewer at the top. The chain supplying rural and less-formal outlets was made of
      more levels than that serving urban and more formal outlets. Wholesale markets
      tended to be relatively concentrated, especially at the top of the chain where
      few importers accounted for most of the anti-malarial volumes sold. Wholesale
      price mark-ups varied across chain levels, ranging from 27% to 99% at the top of
      the chain, 8% at intermediate level (one study only) and 2% to 67% at the level
      supplying retailers directly. Retail mark-ups tended to be higher, and varied
      across outlet types, ranging from 3% to 566% in pharmacies, 29% to 669% in drug
      shops and 100% to 233% in general shops. Information on pricing determinants was
      very limited. CONCLUSIONS: Evidence on the distribution chain for retail sector
      malaria treatment was mainly descriptive and lacked representative data on a
      national scale. These are important limitations in the advent of the Affordable
      Medicine Facility for Malaria, which aims to increase consumer access to
      artemisinin-based combination therapy (ACT), through a subsidy introduced at the
      top of the distribution chain. This review calls for rigorous distribution chain
      analysis, notably on the factors that influence ACT availability and prices in
      order to contribute to efforts towards improved access to effective malaria
      treatment.

PMID- 20149247
TI  - Training of patient and consumer representatives in the basic competencies of
      evidence-based medicine: a feasibility study.
AB  - BACKGROUND: Evidence-based medicine (EBM) has become standard approach in
      medicine. Patients and health authorities increasingly claim active patient roles
      in decision making. Education to cope with these roles might be useful. We
      investigated the feasibility, acceptability and possible impact of EBM training
      courses for patient and consumer representatives. METHODS: We designed a generic
      one-week EBM course based on previous experience with EBM courses for non-medical
      health professionals. A course specific competence test has been developed and
      validated to measure EBM skills. Formative and summative evaluation of the course
      comprised: 1) EBM skills; 2) individual learning goals; 3) self-reported
      implementation after six months using semi-structured interviews; 4) group-based
      feedback by content analysis. EBM skills' achievement was compared to results
      gathered by a group of undergraduate University students of Health Sciences and
      Education who had attended a comparable EBM seminar. RESULTS: Fourteen EBM
      courses were conducted including 161 participants without previous EBM training
      (n = 54 self-help group representatives, n = 64 professional counsellors, n = 36
      patient advocates, n = 7 others); 71% had a higher education degree; all but five
      finished the course. Most participants stated personal learning goals explicitly
      related to practicing EBM such as acquisition of critical appraisal skills (n =
      130) or research competencies (n = 67). They rated the respective relevance of
      the course on average with 80% (SD 4) on a visual analogue scale ranging from 0
      to 100%.Participants passed the competence test with a mean score of 14.7 (SD
      3.0, n = 123) out of 19.5 points. The comparison group of students achieved a
      mean score of 14.4 (SD 3.3, n = 43). Group-based feedback revealed increases of
      self confidence, empowerment through EBM methodology and statistical literacy,
      and acquisition of new concepts of patient information and counselling.
      Implementation of EBM skills was reported by 84 of the 129 (65%) participants
      available for follow-up interviews. Barriers included lack of further support,
      limited possibilities to exchange experiences, and feeling discouraged by
      negative reactions of health professionals. CONCLUSIONS: Training in basic EBM
      competencies for selected patient and consumer representatives is feasible and
      accepted and may affect counselling and advocacy activities. Implementation of
      EBM skills needs support beyond the training course.

PMID- 20149248
TI  - Discrepancy between prevalence and perceived effectiveness of treatment methods
      in myofascial pain syndrome: results of a cross-sectional, nationwide survey.
AB  - BACKGROUND: Myofascial pain is a common dysfunction with a lifetime prevalence
      affecting up to 85% of the general population. Current guidelines for the
      management of myofascial pain are not available. In this study we investigated
      how physicians on the basis of prescription behaviour evaluate the effectiveness
      of treatment options in their management of myofascial pain. METHODS: We
      conducted a cross-sectional, nationwide survey with a standardized questionnaire
      among 332 physicians (79.8% male, 25.6% female, 47.5 +/- 9.6 years) experienced
      in treating patients with myofascial pain. Recruitment of physicians took place
      at three German meetings of pain therapists, rheumatologists and orthopaedists,
      respectively. Physicians estimated the prevalence of myofascial pain amongst
      patients in their practices, stated what treatments they used routinely and then
      rated the perceived treatment effectiveness on a six-point scale (with 1 being
      excellent). Data are expressed as mean +/- standard deviation. RESULTS: The
      estimated overall prevalence of active myofascial trigger points is 46.1 +/-
      27.4%. Frequently prescribed treatments are analgesics, mainly
      metamizol/paracetamol (91.6%), non-steroidal anti-inflammatory drugs/coxibs
      (87.0%) or weak opioids (81.8%), and physical therapies, mainly manual therapy
      (81.1%), TENS (72.9%) or acupuncture (60.2%). Overall effectiveness ratings for
      analgesics (2.9 +/- 0.7) and physical therapies were moderate (2.5 +/- 0.8).
      Effectiveness ratings of the various treatment options between specialities were
      widely variant. 54.3% of all physicians characterized the available treatment
      options as insufficient. CONCLUSIONS: Myofascial pain was estimated a prevalent
      condition. Despite a variety of commonly prescribed treatments, the moderate
      effectiveness ratings and the frequent characterizations of the available
      treatments as insufficient suggest an urgent need for clinical research to
      establish evidence-based guidelines for the treatment of myofascial pain
      syndrome.

PMID- 20149249
TI  - Anti-malarial activity of a non-piperidine library of next-generation quinoline
      methanols.
AB  - BACKGROUND: The clinical utility for mefloquine has been eroded due to its
      association with adverse neurological effects. Better-tolerated alternatives are
      required. The objective of the present study was the identification of lead
      compounds that are as effective as mefloquine, but exhibit physiochemical
      properties likely to render them less susceptible to passage across the blood
      brain barrier. METHODS: A library of drug-like non-piperidine analogs of
      mefloquine was synthesized. These compounds are diverse in structure and
      physiochemical properties. They were screened in appropriate in vitro assays and
      evaluated in terms of their potential as lead compounds. The correlation of
      specific structural attributes and physiochemical properties with activity was
      assessed. RESULTS: The most potent analogs were low molecular weight unconjugated
      secondary amines with no heteroatoms in their side-chains. However, these
      compounds were more metabolically labile and permeable than mefloquine. In terms
      of physiochemical properties, lower polar surface area, lower molecular weight,
      more freely rotatable bonds and fewer H-bond acceptors were associated with
      greater potency. There was no such relationship between activity and LogP, LogD
      or the number of hydrogen bond donors (HBDs). The addition of an H-bond donor to
      the side-chain yielded a series of active diamines, which were as metabolically
      stable as mefloquine but showed reduced permeability. CONCLUSIONS: A drug-like
      library of non-piperidine analogs of mefloquine was synthesized. From amongst
      this library an active lead series of less permeable, but metabolically stable,
      diamines was identified.

PMID- 20149250
TI  - Targeting lentiviral vector to specific cell types through surface displayed
      single chain antibody and fusogenic molecule.
AB  - BACKGROUND: Viral delivery remains one of the most commonly used techniques today
      in the field of gene therapy. However, one of the remaining hurdles is the off
      targeting effect of viral delivery. To overcome this obstacle, we recently
      developed a method to incorporate an antibody and a fusogenic molecule (FM) as
      two distinct molecules into the lentiviral surface. In this report, we expand
      this strategy to utilize a single chain antibody (SCAb) for targeted
      transduction. RESULTS: Two versions of the SCAb were generated to pair with our
      various engineered FMs by linking the heavy chain and the light chain variable
      domains of the anti-CD20 antibody (alphaCD20) via a GS linker and fusing them to
      the hinge-CH2-CH3 region of human IgG. The resulting protein was fused to either
      a HLA-A2 transmembrane domain or a VSVG transmembrane domain for anchoring
      purpose. Lentiviral vectors generated with either version of the SCAb and a
      selected FM were then characterized for binding and fusion activities in CD20
      expressing cells. CONCLUSION: Certain combinations of the SCAb with various FMs
      could result in an increase in viral transduction. This two-molecule lentiviral
      vector system design allows for parallel optimization of the SCAb and FMs to
      improve targeted gene delivery.

PMID- 20149251
TI  - Impaired antiviral activity of interferon alpha against hepatitis C virus 2a in
      Huh-7 cells with a defective Jak-Stat pathway.
AB  - BACKGROUND: The sustained virological response to interferon-alpha (IFN-alpha) in
      individuals infected with hepatitis C virus (HCV) genotype 1 is only 50%, but is
      about 80% in patients infected with genotype 2-6 viruses. The molecular
      mechanisms explaining the differences in IFN-alpha responsiveness between HCV 1
      and other genotypes have not been elucidated. RESULTS: Virus and host cellular
      factors contributing to IFN responsiveness were analyzed using a green
      fluorescence protein (GFP) based replication system of HCV 2a and Huh-7 cell
      clones that either possesses or lack a functional Jak-Stat pathway. The GFP gene
      was inserted into the C-terminal non-structural protein 5A of HCV 2a full-length
      and sub-genomic clones. Both HCV clones replicated to a high level in Huh-7 cells
      and could be visualized by either fluorescence microscopy or flow cytometric
      analysis. Huh-7 cells transfected with the GFP tagged HCV 2a genome produced
      infectious virus particles and the replication of fluorescence virus particles
      was demonstrated in naive Huh-7.5 cells after infection. IFN-alpha effectively
      inhibited the replication of full-length as well as sub-genomic HCV 2a clones in
      Huh-7 cells with a functional Jak-Stat pathway. However, the antiviral effect of
      IFN-alpha against HCV 2a virus was not observed in Huh-7 cell clones with a
      defect in Jak-Stat signaling. HCV infection or replication did not alter IFN
      alpha induced Stat phosphorylation or ISRE promoter-luciferase activity in both
      the sensitive and resistant Huh-7 cell clones. CONCLUSIONS: The cellular Jak-Stat
      pathway is critical for a successful IFN-alpha antiviral response against HCV 2a.
      HCV infection or replication did not alter signaling by the Jak-Stat pathway. GFP
      labeled JFH1 2a replicon based stable cell lines with IFN sensitive and IFN
      resistant phenotypes can be used to develop new strategies to overcome IFN
      resistance against hepatitis C.

PMID- 20149252
TI  - Modeling of loops in proteins: a multi-method approach.
AB  - BACKGROUND: Template-target sequence alignment and loop modeling are key
      components of protein comparative modeling. Short loops can be predicted with
      high accuracy using structural fragments from other, not necessairly homologous
      proteins, or by various minimization methods. For longer loops multiscale
      approaches employing coarse-grained de novo modeling techniques should be more
      effective. RESULTS: For a representative set of protein structures of various
      structural classes test predictions of loop regions have been performed using
      MODELLER, ROSETTA, and a CABS coarse-grained de novo modeling tool. Loops of
      various length, from 4 to 25 residues, were modeled assuming an ideal target
      template alignment of the remaining portions of the protein. It has been shown
      that classical modeling with MODELLER is usually better for short loops, while
      coarse-grained de novo modeling is more effective for longer loops. Even very
      long missing fragments in protein structures could be effectively modeled.
      Resolution of such models is usually on the level 2-6 A, which could be
      sufficient for guiding protein engineering. Further improvement of modeling
      accuracy could be achieved by the combination of different methods. In
      particular, we used 10 top ranked models from sets of 500 models generated by
      MODELLER as multiple templates for CABS modeling. On average, the resulting
      molecular models were better than the models from individual methods.
      CONCLUSIONS: Accuracy of protein modeling, as demonstrated for the problem of
      loop modeling, could be improved by the combinations of different modeling
      techniques.

PMID- 20149253
TI  - Exploring the validity of estimating EQ-5D and SF-6D utility values from the
      health assessment questionnaire in patients with inflammatory arthritis.
AB  - BACKGROUND: Utility scores are used to estimate Quality Adjusted Life Years
      (QALYs), applied in determining the cost-effectiveness of health care
      interventions. In studies where no preference based measures are collected,
      indirect methods have been developed to estimate utilities from clinical
      instruments. The aim of this study was to evaluate a published method of
      estimating the EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D) (preference based)
      utility scores from the Health Assessment Questionnaire (HAQ) in patients with
      inflammatory arthritis. METHODS: Data were used from 3 cohorts of patients with:
      early inflammatory arthritis (<10 weeks duration); established (>5 years
      duration) stable rheumatoid arthritis (RA); and RA being treated with anti-TNF
      therapy. Patients completed the EQ-5D, SF-6D and HAQ at baseline and a follow-up
      assessment. EQ-5D and SF-6D scores were predicted from the HAQ using a published
      method. Differences between predicted and observed EQ-5D and SF-6D scores were
      assessed using the paired t-test and linear regression. RESULTS: Predicted
      utility scores were generally higher than observed scores (range of differences:
      EQ-5D 0.01 - 0.06; SF-6D 0.05 - 0.10). Change between predicted values of the EQ
      5D and SF-6D corresponded well with observed change in patients with established
      RA. Change in predicted SF-6D scores was, however, less than half of that in
      observed values (p < 0.001) in patients with more active disease. Predicted EQ-5D
      scores underestimated change in cohorts of patients with more active disease.
      CONCLUSION: Predicted utility scores overestimated baseline values but
      underestimated change. Predicting utility values from the HAQ will therefore
      likely underestimate the QALYs of interventions, particularly for patients with
      active disease. We recommend the inclusion of at least one preference based
      measure in future clinical studies.

PMID- 20149254
TI  - From basic research to clinical development of MEK1/2 inhibitors for cancer
      therapy.
AB  - The Ras-dependent Raf/MEK/ERK1/2 mitogen-activated protein (MAP) kinase signaling
      pathway is a major regulator of cell proliferation and survival. Not
      surprisingly, hyperactivation of this pathway is frequently observed in human
      malignancies as a result of aberrant activation of receptor tyrosine kinases or
      gain-of-function mutations in RAS or RAF genes. Components of the ERK1/2 pathway
      are therefore viewed as attractive candidates for the development of targeted
      therapies of cancer. In this article, we briefly review the basic research that
      has laid the groundwork for the clinical development of small molecules
      inhibitors of the ERK1/2 pathway. We then present the current state of clinical
      evaluation of MEK1/2 inhibitors in cancer and discuss challenges ahead.

PMID- 20149255
TI  - Gastroesophageal reflux symptoms in infants in a rural population: longitudinal
      data over the first six months.
AB  - BACKGROUND: Increasing numbers of infants are receiving prescription medications
      for symptoms associated with gastroesophageal reflux. Our aim was to
      prospectively measure reported gastroesophageal reflux symptoms in healthy term
      infants for the first six months of life. METHODS: In a prospective cohort study
      in the rural Upper Peninsula of Michigan, 128 consecutive maternal-infant pairs
      were followed for six months and administered the Infant Gastroesophageal Reflux
      Questionnaire Revised (I-GERQ-R) at the one-month, two-month, four-month, and six
      month well-child visits. RESULTS: The I-GERQ-R scores decreased with age. Average
      scores were 11.74 (SE = 5.97) at one-month, 9.97(4.92) at two-months, 8.44(4.39)
      at four-months, and 6.97(4.05) at six months. Symptoms associated with colic were
      greatest at one month of age. CONCLUSION: Symptoms of gastroesophageal reflux as
      measured by the I-GERQ-R decrease with age in the first six months of life in
      otherwise healthy infants; however the I-GERQ-R may have difficulty
      differentiating gastroesophageal reflux disease from colic in those under 3
      months of age.

PMID- 20149256
TI  - Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer.
AB  - BACKGROUND: GPR110 is an orphan G protein-coupled receptor--a receptor without a
      known ligand, a known signaling pathway, or a known function. Despite the lack of
      information, one can assume that orphan receptors have important biological
      roles. In a retroviral insertion mutagenesis screen in the mouse, we identified
      GPR110 as an oncogene. This prompted us to study the potential isoforms that can
      be gleaned from known GPR110 transcripts, and the expression of these isoforms in
      normal and transformed human tissues. METHODS: Various epitope-tagged isoforms of
      GPR110 were expressed in cell lines and assayed by western blotting to determine
      cleavage, surface localization, and secretion patterns. GPR110 transcript and
      protein levels were measured in lung and prostate cancer cell lines and clinical
      samples, respectively, by quantitative PCR and immunohistochemistry. RESULTS: We
      found four potential splice variants of GPR110. Of these variants, we confirmed
      three as being expressed as proteins on the cell surface. Isoform 1 is the
      canonical form, with a molecular mass of about 100 kD. Isoforms 2 and 3 are
      truncated products of isoform 1, and are 25 and 23 kD, respectively. These
      truncated isoforms lack the seven-span transmembrane domain characteristic of GPR
      proteins and thus are not likely to be membrane anchored; indeed, isoform 2 can
      be secreted. Compared with the median gene expression of approximately 200
      selected genes, GPR110 expression was low in most tissues. However, it had higher
      than average gene expression in normal kidney tissue and in prostate tissues
      originating from older donors. Although identified as an oncogene in murine T
      lymphomas, GPR110 is greatly overexpressed in human lung and prostate cancers. As
      detected by immunohistochemistry, GPR110 was overexpressed in 20 of 27 (74%) lung
      adenocarcinoma tissue cores and in 17 of 29 (59%) prostate adenocarcinoma tissue
      cores. Additionally, staining with a GPR110 antibody enabled us to differentiate
      between benign prostate hyperplasia and potential incipient malignancy.
      CONCLUSION: Our work suggests a role for GPR110 in tumor physiology and supports
      it as a potential therapeutic candidate and disease marker for both lung and
      prostate cancer.

PMID- 20149257
TI  - Expression genetics identifies spinal mechanisms supporting formalin late phase
      behaviors.
AB  - BACKGROUND: Formalin injection into rodent hind paws is one of the most commonly
      employed pain assays. The resulting nocifensive behaviors can be divided into two
      phases differing in timing, duration and underlying mechanisms. Spinal
      sensitization has long been felt to participate in the second phase of this
      response, although this sensitization is incompletely understood. By using
      correlative analysis between spinal gene expression and mouse strain-dependent
      intensity of late phase behavior, we hypothesized genes participating in
      variability of the response could be identified. RESULTS: Late phase formalin
      behavior scores among 10 inbred mouse strains were correlated with a spinal cord
      gene expression database constructed using expression arrays. Messenger RNA
      levels for several genes were highly correlated with the late phase behavioral
      responses. Most of these genes had already been implicated in mechanisms
      regulating pain and analgesia. One of the most strongly correlated genes, Mapk8
      coding for c-Jun N-terminal kinase 1 (JNK1), was chosen for further analysis.
      Studies using additional strains of mice confirmed that spinal cord mRNA
      expression levels of Mapk8 followed the pattern predicted by strain-specific
      levels of formalin behavior. Interestingly, spinal cord JNK1 protein levels
      displayed an inverse relationship with mRNA measurements. Finally, intrathecal
      injections of the selective JNK inhibitor, SP600125, selectively reduced late
      phase licking behavior. CONCLUSIONS: Wide differences in pain behaviors,
      including those resulting from the injection of formalin, can be observed in
      inbred strains of mice suggesting strong genetic influences. Correlating levels
      of gene expression in tissues established to be mechanistically implicated in the
      expression of specific behaviors can identify genes involved in the behaviors of
      interest. Comparing formalin late phase behavior levels with spinal cord gene
      expression yielded several plausible gene candidates, including the Mapk8 gene.
      Additional molecular and pharmacologic evidence confirmed a functional role for
      this gene in supporting formalin late phase responses.

PMID- 20149258
TI  - Short term hypothyroidism affects ovarian function in the cycling rat.
AB  - BACKGROUND: Rats made hypothyroid with propilthyouracil start showing abnormal
      cycling on the second cycle after the start of the treatment, with a high
      proportion of spontaneous pseudopregnancies and reduced fertility. METHODS: To
      investigate some of the mechanisms involved in these reproductive abnormalities,
      hypothyroidism was induced in virgin rats by propilthyouracil (0.1 g/L in the
      drinking water) and we determined circulating hormones by radioimmunoassay and
      whole ovary expression of ovarian hormone receptors, growth factors and
      steroidogenic enzymes using semi-quantitative RT-PCR.The study was performed on
      days 6 to 9 of treatment, corresponding to diestrus I (at 20.00-22.00 h),
      diestrus II (at 20.00-22.00 h), proestrus and estrus (both at 8.00-10.00 h and
      20.00-22.00 h) of the second estrous cycle after beginning propilthyouracil
      treatment. Another group of rats was mated on day 8 and the treatment continued
      through the entire pregnancy to evaluate reproductive performance. RESULTS:
      Hypothyroidism increased circulating prolactin and estradiol on estrus 5 to 7
      fold and 1.2 to 1.4-fold respectively. Growth hormone and insulin-like growth
      factor 1 diminished 60 and 20% respectively on proestrus morning. Hypothyroidism
      doubled the ovarian mRNA contents of estrogen receptor-beta on proestrus and
      estrus evenings, cyp19A1 aromatase mRNA on estrus evening and of growth hormone
      receptor on proestrus evening. Hypothyroidism did not influence ovulation rate or
      the number of corpora lutea at term, but a diminished number of implantation
      sites and pups per litter were observed (Hypothyroid: 11.7 +/- 0.8 vs. CONTROL:
      13.9 +/- 0.7). CONCLUSIONS: Short term hypothyroidism alters normal hormone
      profile in the cycling rat increasing the expression of estrogen receptor-beta
      and cyp19A1 aromatase on estrus, which in turn may stimulate estradiol and
      prolactin secretion, favouring corpus luteum survival and the subsequent
      instauration of pseudopregnancy.

PMID- 20149259
TI  - Hypofractionated radiotherapy has the potential for second cancer reduction.
AB  - BACKGROUND AND PURPOSE: A model for carcinoma and sarcoma induction was used to
      study the dependence of carcinogenesis after radiotherapy on fractionation.
      MATERIALS AND METHODS: A cancer induction model for radiotherapy doses including
      fractionation was used to model carcinoma and sarcoma induction after a radiation
      treatment. For different fractionation schemes the dose response relationships
      were obtained. Tumor induction was studied as a function of dose per fraction.
      RESULTS: If it is assumed that the tumor is treated up to the same biologically
      equivalent dose it was found that large dose fractions could decrease second
      cancer induction. The risk decreases approximately linear with increasing
      fraction size and is more pronounced for sarcoma induction. Carcinoma induction
      decreases by around 10% per 1 Gy increase in fraction dose. Sarcoma risk is
      decreased by about 15% per 1 Gy increase in fractionation. It is also found that
      tissue which is irradiated using large dose fractions to dose levels lower than
      10% of the target dose potentially develop less sarcomas when compared to tissues
      irradiated to all dose levels. This is not observed for carcinoma induction.
      CONCLUSIONS: It was found that carcinoma as well as sarcoma risk decreases with
      increasing fractionation dose. The reduction of sarcoma risk is even more
      pronounced than carcinoma risk. Hypofractionation is potentially beneficial with
      regard to second cancer induction.

PMID- 20149261
TI  - Non-rigid registration of breast surfaces using the laplace and diffusion
      equations.
AB  - A semi-automated, non-rigid breast surface registration method is presented that
      involves solving the Laplace or diffusion equations over undeformed and deformed
      breast surfaces. The resulting potential energy fields and isocontours are used
      to establish surface correspondence. This novel surface-based method, which does
      not require intensity images, anatomical landmarks, or fiducials, is compared to
      a gold standard of thin-plate spline (TPS) interpolation. Realistic finite
      element simulations of breast compression and further testing against a tissue
      mimicking phantom demonstrate that this method is capable of registering surfaces
      experiencing 6 - 36 mm compression to within a mean error of 0.5 - 5.7 mm.

PMID- 20149260
TI  - Effects of collagen membranes enriched with in vitro-differentiated N1E-115 cells
      on rat sciatic nerve regeneration after end-to-end repair.
AB  - Peripheral nerves possess the capacity of self-regeneration after traumatic
      injury but the extent of regeneration is often poor and may benefit from
      exogenous factors that enhance growth. The use of cellular systems is a rational
      approach for delivering neurotrophic factors at the nerve lesion site, and in the
      present study we investigated the effects of enwrapping the site of end-to-end
      rat sciatic nerve repair with an equine type III collagen membrane enriched or
      not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic
      nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture
      enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and
      end-to-end suture enwrapped with an equine collagen type III membrane previously
      covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to
      EndMembCell group). Along the postoperative, motor and sensory functional
      recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex
      latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and
      the repaired sciatic nerves were processed for histological and stereological
      analysis. Results showed that enwrapment of the rapair site with a collagen
      membrane, with or without neural cell enrichment, did not lead to any significant
      improvement in most of functional and stereological predictors of nerve
      regeneration that we have assessed, with the exception of EPT which recovered
      significantly better after neural cell enriched membrane employment. It can thus
      be concluded that this particular type of nerve tissue engineering approach has
      very limited effects on nerve regeneration after sciatic end-to-end nerve
      reconstruction in the rat.

PMID- 20149262
TI  - Maintenance of Sorafenib following combined therapy of three-dimensional
      conformal radiation therapy/intensity-modulated radiation therapy and
      transcatheter arterial chemoembolization in patients with locally advanced
      hepatocellular carcinoma: a phase I/II study.
AB  - BACKGROUND: Three-dimensional conformal radiation therapy (3DCRT)/intensity
      modulated radiation therapy (IMRT) combined with or without transcatheter
      arterial chemoembolization (TACE) for locally advanced hepatocellular carcinoma
      (HCC) has shown favorable outcomes in local control and survival of locally
      advanced HCC. However, intra-hepatic spreading and metastasis are still the
      predominant treatment failure patterns. Sorafenib is a multikinase inhibitor with
      effects against tumor proliferation and angiogenesis. Maintenance Sorafenib would
      probably prevent or delay the intrahepatic and extrahepatic spread of HCC after
      radiotherapy, which provides the rationale for the combination of these treatment
      modalities. METHODS AND DESIGN: Patients with solitary lesion (bigger than 5 cm
      in diameter) histologically or cytologically confirmed HCC receive TACE (1-3
      cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be
      administered only for the patients with non-progression disease 4 to 6 weeks
      after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day.
      Sorafenib will be continuously given for 12 months unless intolerable toxicities
      and/or tumor progression. If no more than 3 patients discontinue Sorafenib
      treatment who experience dose-limiting toxicity after necessary dose modification
      and delay and/or radiation-induced liver disease in the first 15 enrolled
      patients, the study will recruit second fifteen patients for further evaluating
      safety and efficacy of treatment. Hypothesis of the current study is that
      Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE
      is safe and superior to radiotherapy combined with TACE alone in terms of time to
      progression (TTP), progression-free survival (PFS) and overall survival (OS) in
      comparison to historical data. DISCUSSION: A recent meta-analysis showed TACE in
      combination with radiotherapy, improved the survival and the tumor response of
      patients, and was thus more therapeutically beneficial. In this study, local
      therapy for HCC is the combination of TACE and radiotherapy. Radiation exposure
      as a kind of stress might induce the compensatory activations of multiple
      intracellular signaling pathway mediators, such as PI3K, MAPK, JNK and NF-kB.
      Vascular endothelial growth factor (VEGF) was identified as one factor that was
      increased in a time- and dose-dependent manner after sublethal irradiation of HCC
      cells in vitro, translating to enhanced intratumor angiogenesis in vivo.
      Therefore, Sorafenib-mediated blockade of the Raf/MAPK and VEGFR pathways might
      enhance the efficacy of radiation, when Sorafenib is followed sequentially as a
      maintenance modality. (ClinicalTrials.gov number, NCT00999843.).

PMID- 20149263
TI  - Carcinoid tumor of the minor papilla in complete pancreas divisum presenting as
      recurrent abdominal pain.
AB  - BACKGROUND: Tumors of the minor papilla of the duodenum are extremely rare, and
      they are mostly neuroendocrine tumors, such as somatostatinomas and carcinoid
      tumors. However, true incidence of carcinoid tumors in minor papilla might be
      much higher, because patients with minor papillary tumors usually remain
      asymptomatic. We report a very unusual case of carcinoid tumor in a patient with
      complete pancreas divisum with a review of the literature. CASE PRESENTATION: A
      56-year-old female patient was referred for evaluation of pancreatic duct
      dilatation noted on abdominal ultrasonography and computerized tomography. She
      complained of intermittent epigastric pain for 6 months. A MRCP and ERCP revealed
      complete pancreas divisum with dilatation of the main pancreatic duct. On
      duodenoscopy, a small, yellows, subepithelial nodule was visualized at the minor
      papilla; biopsy of this lesion revealed a carcinoid tumor. She underwent a
      pylorus-preserving pancreaticoduodenectomy. The histologic evaluation showed a
      single nodule, 1 cm in diameter, in the submucosa with duodenal and vascular
      invasion and metastasis to the regional lymph nodes. CONCLUSION: Although the
      size of the carcinoid tumor was small and the tumor was hormonally inactive, the
      concomitant pancreas divisum led to an early diagnosis, the tumor had aggressive
      behavior. Carcinoid tumors of the minor papilla should be included in the
      differential diagnosis of recurrent abdominal pain or pancreatitis of unknown
      cause.

PMID- 20149265
TI  - Characterization of antimicrobial resistance, molecular and phage types of
      Salmonella enterica serovar Typhi isolations.
AB  - Isolation rates in Canada of Salmonella enterica serovar Typhi increased from
      0.29 to 0.55 isolations/100,000 population during 2000-2006. Although no
      ciprofloxacin resistance was detected, nalidixic acid resistance increased from
      41% to 80%. Multidrug-resistant S. Typhi represented 18% of the strains tested.
      Pulsed-field gel electrophoresis (PFGE) analysis of 222 isolates resulted in 91
      distinct patterns clustering into four major genetic similarity groups. The five
      most frequently occurring PFGE patterns accounted for 46% of the isolates. Drug
      resistant isolates predominantly occurred in one PFGE similarity group. There
      were 39 phage types identified in 826 isolates analysed with 60% described by
      five phage types; 134 were untypable. The phage types associated with multidrug
      resistance were phage types 53, B1, D1, E1, E9, G3 and M1. Improved integration
      of epidemiological and laboratory case data will facilitate the protection of
      public health in Canada during an era of increasing travel and globalization.

PMID- 20149264
TI  - Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in
      Drosophila.
AB  - BACKGROUND: The TSC-22 domain family (TSC22DF) consists of putative transcription
      factors harboring a DNA-binding TSC-box and an adjacent leucine zipper at their
      carboxyl termini. Both short and long TSC22DF isoforms are conserved from flies
      to humans. Whereas the short isoforms include the tumor suppressor TSC-22
      (Transforming growth factor-beta1 stimulated clone-22), the long isoforms are
      largely uncharacterized. In Drosophila, the long isoform Bunched A (BunA) acts as
      a growth promoter, but how BunA controls growth has remained obscure. RESULTS: In
      order to test for functional conservation among TSC22DF members, we expressed the
      human TSC22DF proteins in the fly and found that all long isoforms can replace
      BunA function. Furthermore, we combined a proteomics-based approach with a
      genetic screen to identify proteins that interact with BunA. Madm (Mlf1 adapter
      molecule) physically associates with BunA via a conserved motif that is only
      contained in long TSC22DF proteins. Moreover, Drosophila Madm acts as a growth
      promoting gene that displays growth phenotypes strikingly similar to bunA
      phenotypes. When overexpressed, Madm and BunA synergize to increase organ growth.
      CONCLUSIONS: The growth-promoting potential of long TSC22DF proteins is
      evolutionarily conserved. Furthermore, we provide biochemical and genetic
      evidence for a growth-regulating complex involving the long TSC22DF protein BunA
      and the adapter molecule Madm.

PMID- 20149266
TI  - Staphylococcus aureus carriage in care homes: identification of risk factors,
      including the role of dementia.
AB  - The aim of this study was to investigate the prevalence and associated risk
      factors of methicillin-susceptible and methicillin-resistant Staphylocccus aureus
      (MSSA and MRSA) carriage in care homes, with particular focus on dementia. A
      point-prevalence survey of 748 residents in 51 care homes in Gloucestershire and
      Greater Bristol was undertaken. Dementia was assessed by the clock test or
      abbreviated mini-mental test. Nasal swabs were cultured for S. aureus on
      selective agar media. Multivariable analysis indicated that dementia was not a
      significant risk factor for MSSA (16.2%) or MRSA (7.8%); and that residents able
      to move around the home unassisted were at a lower risk of MRSA (P=0.04). MSSA
      carriage increased with increasing age (P=0.03) but MRSA carriage decreased with
      increasing age (P=0.05). Hospitalization in the last 6 months increased the risk
      of MSSA (P=0.04) and MRSA (P=0.10). We concluded that cross-infection through
      staff caring for more dependent residents may spread MRSA within care homes and
      from the recently hospitalized. Control of MSSA and MRSA in care homes requires
      focused infection control interventions.

PMID- 20149267
TI  - A cognitive deficit induced in rats by chronic intermittent cold stress is
      reversed by chronic antidepressant treatment.
AB  - We have previously reported that 14-d chronic intermittent cold (CIC) stress
      induced a cognitive deficit in reversal learning on the rat attentional set
      shifting test. This effect may be related to dysregulation of 5-HT function in
      orbitofrontal cortex, as a model of cognitive dysfunction in depression. To test
      the ability of chronic antidepressant drug treatment to reverse the cognitive
      deficit induced by CIC, it was first necessary to assess the temporal
      characteristics of the CIC-induced cognitive deficit. Thus, in the first
      experiment, we assessed the duration of the cognitive deficit following 2-wk CIC
      stress. Replicating previous experiments, CIC induced a reversal learning deficit
      tested 3 d after the last cold exposure. However, cognitive performance of CIC
      stressed rats was no different from unstressed controls when tested 7, 14 or 21 d
      after termination of the stress treatment. We next compared behaviour 3 d after 2
      wk CIC to that seen 3 d after 5-wk CIC, and found similar deficits in reversal
      learning. Thus, in the final experiment, antidepressant drug treatment was
      initiated after 2-wk CIC stress, and was maintained for 3 wk, concurrent with the
      continuation of CIC stress. Both chronic and acute treatment with the selective
      serotonin reuptake inhibitor, citalopram, but not the norepinephrine reuptake
      blocker, desipramine, reversed the cognitive deficit induced by CIC stress. Thus,
      this stress-induced cognitive deficit may be a useful model for cognitive
      deficits related to prefrontal cortical hypoactivity in depression, and for
      investigating neurobiological mechanisms underlying the beneficial effects of
      chronic antidepressant drug treatment.

PMID- 20149269
TI  - Imaging the D3 receptor in humans in vivo using [11C](+)-PHNO positron emission
      tomography (PET).

PMID- 20149268
TI  - Characterization of the electrophysiological properties of triple reuptake
      inhibitors on monoaminergic neurons.
AB  - Triple reuptake inhibitors represent a potential new class of antidepressant
      drugs that block norepinephrine (NE), dopamine (DA) and serotonin [5
      hydroxytryptamine (5-HT)] transporters. The present in-vivo electrophysiological
      study was undertaken to determine the effects of the triple reuptake inhibitors
      SEP-225289 and DOV216303 on the neuronal activities of locus coeruleus (LC) NE,
      ventral tegmental area (VTA) DA and dorsal raphe (DR) 5-HT neurons. Administered
      acutely, SEP-225289 and DOV216303 dose-dependently decreased the spontaneous
      firing rate of LC NE, VTA DA and DR 5-HT neurons through the activation of
      alpha2, D2 and 5-HT(1A) autoreceptors, respectively. Both compounds predominantly
      inhibited the firing rate of LC NE neurons while producing only a partial
      decrease in VTA DA and DR 5-HT neuronal discharge. SEP-225289 was equipotent at
      inhibiting 5-HT and NE transporters since it prolonged to the same extent the
      time required for a 50% recovery (RT50) of the firing activity of dorsal
      hippocampus CA3 pyramidal neurons from the inhibition induced by
      microiontophoretic application of 5-HT and NE. Finally, in the presence of
      WAY100635, a 5-HT(1A) receptor antagonist, SEP-225289 activated 5-HT neurons at
      doses that normally did not inhibit them. Taken together, the present results
      indicate that reciprocal interactions among NE, DA and 5-HT inputs need to be
      considered to anticipate the net effect of triple reuptake inhibitors on the
      enhancement of brain monoamine transmission. The results also suggest that the
      therapeutic action of triple reuptake inhibitors may be potentiated by
      antagonizing the cell body 5-HT(1A) autoreceptors.

PMID- 20149270
TI  - Development of a tool to evaluate geropsychology knowledge and skill
      competencies.
AB  - BACKGROUND: Workforce shortages to meet the mental health needs of the world's
      aging population are well documented. Within the field of professional
      geropsychology in the U.S.A., a national conference was convened in 2006 to
      delineate competencies for psychological practice with older adults and a
      training model for the field. The conference produced the Pikes Peak Model of
      Geropsychology Training. The Council of Professional Geropsychology Training
      Programs (CoPGTP) aimed to produce a competency evaluation tool to help
      individuals define training needs for and evaluate progress in development of the
      Pikes Peak professional geropsychology competencies. METHODS: A CoPGTP task force
      worked for one year to adapt the Pikes Peak Model geropsychology attitude,
      knowledge, and skill competencies into an evaluation tool for use by supervisors,
      students and professional psychologists at all levels of geropsychology training.
      The task force developed a competency rating tool, which included delineation of
      behavioral anchors for each of the Pikes Peak geropsychology knowledge and skill
      competencies and use of a developmental rating scale. Pilot testing was
      conducted, with 13 individuals providing feedback on the clarity and feasibility
      of the tool for evaluation of oneself or students. RESULTS: The Geropsychology
      Knowledge and Skills Assessment Tool, Version 1.1, is now posted on the CoPGTP
      website and is being used by geropsychology training programs in the U.S.A.
      CONCLUSIONS: The evaluation tool has both strengths and limitations. We discuss
      future directions for its ongoing validation and professional use.

PMID- 20149273
TI  - FTIR vs. FT-IR vs. mid-IR.

PMID- 20149271
TI  - Challenges associated with the recognition and treatment of depression in older
      recipients of home care services.
AB  - BACKGROUND: Home care for older adults is a common phenomenon worldwide because
      it allows older adults to remain in their home environment. Research has shown
      that depression is frequently found in older recipients of home care services.
      Nonetheless, it is often poorly recognized and treated. Untreated or poorly
      treated depression in older home care recipients has been associated with a
      variety of negative outcomes, including increased morbidity and mortality,
      greater likelihood of nursing home institutionalization and higher caregiver
      distress. METHODS: The present review outlines some of the challenges associated
      with appropriate recognition and treatment of depression in older home care
      recipients. RESULTS: Our review demonstrates that more aggressive management of
      depressive symptoms and the employment of an interdiciplinary team can result in
      beneficial outcomes. CONCLUSIONS: Further research is needed, especially in the
      area of psychotherapeutic interventions as these should be flexible enough to
      meet the unique and evolving needs of this frail population of older adults.

PMID- 20149274
TI  - In situ infrared emission spectroscopy for quantitative gas-phase measurement
      under high temperature reaction conditions: an analytical method for methane by
      means of an innovative small-volume flowing cell.
AB  - We have used infrared emission spectroscopy (IRES) in order to perform in situ
      studies under flowing gas-phase conditions. When the small-volume cell developed
      herein is used, we can (1) observe emission spectra from a hot gas-phase sample
      having an effective volume much less than one milliliter, (2) observe spectra of
      typical molecular species present, and (3) observe spectra of the more important
      molecular species down to below 10% and in some cases even as low as 1%. In
      addition, an analytical method has been derived in order to conduct quantitative
      studies under typical reaction conditions. We show that simplifications can be
      made in the data acquisition and handling for a direct linear correlation between
      band intensity and concentration with only simple background correction. The
      practical lower limit for methane in the present setup is approximately 0.5-1%
      v/v depending on the selected temperature. Our data were collected at 500, 600,
      and 700 degrees C, respectively. The major features of the present cell design
      are fairly simple and basically formed by a quartz tube (outer diameter=6 mm,
      inner diameter=4 mm) inside a metal pipe and two tubular ceramic heaters. This
      simple setup has advantages and attractive features that have extended the
      application of IRES to new fields and, in particular, for in situ studies of
      hydrocarbon reactions at different residence times at high temperature.

PMID- 20149275
TI  - Study of air-induced paper discolorations by infrared spectroscopy, X-ray
      fluorescence, and scanning electron microscopy.
AB  - Air-induced paper discoloration is described as being different from other
      discoloration morphologies. It seems to be the result of prolonged exposure to
      air in a humid and polluted environment without appropriate protecting coverage.
      In this work, three folios from the same eighteenth century book, presenting
      three degrees of discoloration and opacity and subjected to different
      environmental conditions, were examined and compared. Samples were analyzed and
      compared by three different instrumental techniques, mid-infrared spectroscopy, X
      ray fluorescence (XRF), and scanning electron microscopy (SEM). Chemical and
      physical changes were confirmed from the data collected by these techniques. The
      absence of the secondary amide band characteristic of proteins in the infrared
      spectra of the two discolored folios, accompanied by the appearance and increase
      of white mineral-like deposits visible in the SEM micrographs, support the idea
      that oxidation reactions occurred and that these two folios were subjected to
      more severe degradation hazard.

PMID- 20149276
TI  - Laser-induced breakdown spectroscopy of steel: a comparison of univariate and
      multivariate calibration methods.
AB  - Laser-induced breakdown spectroscopy (LIBS) was carried out on twenty-three low
      to high alloy steel samples to quantify their concentrations of chromium, nickel,
      and manganese. LIBS spectral data were correlated to known concentrations of the
      samples and three calibration methods were compared. A standard LIBS calibration
      technique using peak area integration normalized by an internal standard was
      compared to peak area integration normalized by total light and the multivariate
      statistical technique of partial least squares. For the partial least squares
      analysis, the PLS-1 algorithm was used, where a predictive model is generated for
      each element separately. Partial least squares regression coefficients show that
      the algorithm correctly identifies the atomic emission peaks of interest for each
      of the elements. Predictive capabilities of each calibration approach were
      quantified by calculating the standard and relative errors of prediction. The
      performance of partial least squares is on par with using iron as an internal
      standard but has the key advantage that it can be applied to samples where the
      concentrations of all elements are unknown.

PMID- 20149277
TI  - A study of ablation, spatial, and temporal characteristics of laser-induced
      plasmas generated by multiple collinear pulses.
AB  - Multi-pulse laser-induced breakdown spectroscopy (LIBS) in the collinear pulse
      configuration with time-integrating detection was performed on metallic samples
      in ambient air in an effort to clarify the contributing processes responsible for
      the signal enhancement observed in comparison with single-pulse excitation.
      Complementary experiments were also carried out on another LIBS setup using
      detection by an imaging spectrograph with high time resolution. The effects of
      laser bursts consisting of up to seven ns-range pulses from Nd-doped solid-state
      lasers operating at their fundamental wavelength and separated by 8.5-50 micros
      time gaps was studied. The ablation and emission characteristics of the generated
      plasmas were investigated using light profilometry, microscopy, plasma imaging,
      emission distribution mapping, time-resolved line emission monitoring, and plasma
      temperature calculations. The experimental data suggest that the two contributing
      processes mainly responsible for the signal enhancement effect are the plume
      reheating caused by the sequential laser pulses and, more dominantly, the
      increased material ablation attributed to the lower breakdown threshold for the
      preheated (molten) sample surface and/or the reduced background gas pressure
      behind the shockwave of preceding pulses.

PMID- 20149278
TI  - Instantaneous temperature imaging of diffusion flames using two-line atomic
      fluorescence.
AB  - This work investigates the first demonstration of nonlinear regime two-line
      atomic fluorescence (NTLAF) thermometry in laminar non-premixed flames. The
      results show the expediency of the technique in the study of the reaction zone
      and reveals interesting findings about the indium atomization process. Indium
      fluorescence is observed to be strongest at the flame-front, where the
      temperature exceeds 1000 K. The uncertainty in the deduced temperature
      measurement is approximately 6%. The temperature profile across the reaction zone
      shows good agreement with laminar flame calculations. The advantages and inherent
      limitations of the technique are discussed.

PMID- 20149279
TI  - A methodology to estimate concentration profiles from two-dimensional covariance
      spectroscopy applied to kinetic data.
AB  - Two-dimensional (2D) covariance analyses applied to spectroscopy data obtained
      while monitoring chemical processes allow exploring the chemical reactions
      involved. Some slices of the sample-sample covariance map are an approach to the
      concentration profiles of the reactive species and we present a novel methodology
      to identify them. The method overcomes problems habitually referenced in the
      application of this technique and it is based on the selection of spectral zones
      with similar standard deviation of the variables and row centering the spectra
      data in each zone. The slices are identified according to the correlation
      coefficient value. The method is illustrated using simulated spectra data set
      representatives of two model reactions A --> B and A --> I --> B. It has been
      applied to analyze the effect of rare earth metal triflate initiators in the
      cationic curing process of diglycidyl ether of bisphenol A with gamma
      valerolactone. The number of significant slices found is equal to the number of
      reactive species. This is interesting information that can be used as an initial
      estimation to find profile concentrations using other methods such as
      multivariate curve resolution-alternating least squares (MCR-ALS).

PMID- 20149280
TI  - Temperature-dependent Raman study of the smectic to nematic phase transition and
      vibrational analysis using density functional theory of the liquid crystalline
      system 4-decyloxy benzoic acid.
AB  - Room-temperature Raman spectra of the thermotropic liquid crystalline system, 4
      decyloxy benzoic acid (4DBA) have been recorded and the experimentally observed
      bands are assigned by density functional theory (DFT) for the first time. The C-O
      and C-C stretching and C-H in-plane bending modes of the phenyl ring and C=O
      stretching modes of the -COOH group are the marker bands for the smectic (S) -->
      nematic (N) and nematic (N) --> isotropic (I) transitions for this system. The
      temperature-dependent Raman spectra for these bands in the heating cycle clearly
      characterize the S-->N and the N-->I transition over a range <1 degree C, which
      is much better than the earlier range of 23 degrees C for S-->N and 26 degrees C
      for the N-->I transition. The approximately 773, approximately 807, approximately
      881, and approximately 1146 cm(-1) bands disappear, whereas a band at
      approximately 830 cm(-1) appears at the S-->N transition. The relative intensity
      of the approximately 1257 and approximately 1280 cm(-1) bands distinguishes the
      three phases, namely smectic, nematic, and isotropic, in 4DBA. The variation of
      line width and peak wavenumber of the approximately 1128 and approximately 1168
      cm(-1) bands also clearly shows the two transitions. The molecular reorientation
      at the transition and the effect of local fields present in the liquid
      crystalline mesophases are also briefly discussed on the basis of changes in
      intensity, linewidth and peak wavenumber with temperature.

PMID- 20149281
TI  - Removing cosmic ray features from Raman map data by a refined nearest neighbor
      comparison method as a precursor for chemometric analysis.
AB  - An algorithm to remove cosmic ray (CR) features from Raman spectra collected in
      mapping experiments using a charge-coupled device (CCD) is presented. Each
      spectrum is compared to spectra collected from adjacent points in space using
      correlation values. The most similar neighbor (MSN) spectrum is selected, offset,
      and used for identification of CRs. The offset values are defined in terms of the
      noise level for data with a low signal-to-noise ratio and in terms of the peak
      height for data with a high signal-to-noise ratio. Scaled intensity values of the
      MSN spectra are used for replacement of contaminated pixels, allowing for full
      recovery of underlying spectral features. The algorithm is applicable for any
      Raman map where the particle sizes within the analyzed mixture are larger than
      the sampling size or to any other data where the sampling is more frequent than
      the variation, e.g., time series or temperature profiles. Its application to
      several maps of pharmaceutical samples is discussed here. With an appropriate
      offset value for the MSN spectra, no misdetections occur, and all CRs more
      intense than the offset are removed, which includes the CRs that would have
      hampered subsequent chemometric analysis by methods such as principal component
      analysis (PCA).

PMID- 20149282
TI  - A low cost time-resolved Raman spectroscopic sensing system enabling fluorescence
      rejection.
AB  - This paper describes a novel, compact, fiber-coupled, time-resolved Raman
      spectroscopy system that takes advantage of recent developments in diode laser
      and data acquisition technology to exploit the natural temporal separation
      between Raman and fluorescence phenomena and thereby limits the influence of
      fluorescence on Raman observations. The unit has been designed to be particularly
      low cost and is intended to provide the foundation for a wide range of in-line or
      fieldable sensing devices that can enhance the potential and affordability of in
      situ chemical analyses. The system operating principles, design, and performance
      are discussed along with its advantages and tradeoffs relative to traditional
      continuous wave (CW) Raman techniques. The system relies on a 6.4 kHz repetition
      rate 900 ps pulsed diode laser operating in the visible wavelength range (532 nm)
      to enhance the quality of Raman observations relative to CW and infrared systems,
      particularly for analytes examined in the presence of fluorophores. Time-resolved
      photon counting, achieved through a combination of off-the-shelf and custom
      hardware and software, limits the influence of fluorescence on Raman observations
      under pulsed excitation. The paper presents examples of the quality of Raman
      signatures that can be obtained with the system for a variety of compounds such
      as trichloroethylene, benzene, an aqueous nitrate solution, and olive oil.
      Further, the paper demonstrates an approximately 15-fold improvement in signal-to
      noise ratio when comparing long- and short-gated time-resolved photon counting
      acquisition scenarios for a neat benzene sample doped with rhodamine 6G at a
      concentration of 1 x 10(-4) M. The system's versatility and effectiveness in the
      assessment of complex mixtures representative of industrial or field settings is
      demonstrated through analysis of a gasoline sample. Additional discussion
      outlines how efficient signal averaging over extended observation periods can
      enable low concentration chemical analyses, particularly relevant in field
      settings.

PMID- 20149283
TI  - Surface-controlled electroless deposition method in the preparation of stacked
      silver nanoparticles on germanium for surface-enhanced infrared absorption
      measurements.
AB  - A new method to prepare highly sensitive sensing elements for surface-enhanced
      infrared absorption (SEIRA) measurements was investigated. A surface-controlled
      procedure was employed to grow round and stacked silver nanoparticles (Ag-NPs) on
      germanium substrates. In this method, an initial layer of Ag-NPs was prepared
      using a common method of electroless deposition. After subsequently placing a
      controlled layer of p-aminothiophenol (pATP) on the surface of the initial layer
      of Ag-NPs, the substrates were placed in a silver nitrate solution to grow a
      second layer of Ag-NPs. By repeating these growing procedures, multi-layers of
      stacked Ag-NPs can be obtained. To examine the influence of morphology of the
      formed Ag-NPs on the resulting SEIRA signals, the factors affecting the reactions
      were systematically examined. These factors included the concentrations of silver
      nitrates, the reaction times to prepare both the initial layer and the second
      layer of Ag-NPs, and the coverage of pATP. Results indicate that the Ag-NPs
      making up the second layer were round in shape and much more densely distributed
      than those in the initial layer. The observed SEIRA spectra did not show
      derivative-shaped absorption bands for pATP on the Ag-NPs after re-growth,
      indicating that pATP was sandwiched between the two layers of Ag-NPs, preventing
      the nanoparticles from coming into direct contact with one another. Also, the
      SEIRA signals of the controlled molecules between the particles were found to be
      two to five times more intense than the signals before growing another layer of
      Ag-NPs. The reaction conditions can be adjusted to vary the morphology and
      thickness of the Ag-NP layers, and, by repeating the growing procedures, a thick
      layer of stacked Ag-NPs with suitable size for SEIRA measurements can be obtained
      that is highly suited to chemical sensing applications.

PMID- 20149284
TI  - Characterization of thio compounds for a surface-controlled electroless
      deposition method in the preparation of silver nanoparticles on germanium for
      surface-enhanced infrared absorption measurements.
AB  - An electroless re-growing method has been developed to prepare silver
      nanoparticles (Ag-NPs) on substrates for surface-enhanced infrared absorption
      (SEIRA) measurements. To understand the roles of specific molecules in
      controlling the properties of Ag-NPs on germanium substrates, thio compounds
      bearing different functional groups were examined systematically. Four classes of
      thio compounds were examined in this work, including aromatic thio compounds with
      second functional group, alkyl thio compounds with second functional group,
      structural isomers of aromatic thio compounds, and alkyl thio compounds with
      different alkyl chain lengths. By correlating SEIRA signals with the observed
      morphologies of the Ag-NPs, it was found that thio compounds bearing amine polar
      functional groups produced Ag-NPs that were the most regular in shape and size.
      Also, aromatic thio compounds provided better performance than did alkyl thio
      compounds in terms of producing suitable shapes and sizes for SEIRA. The Ag-NPs
      prepared in this work were generally around 50 nm in diameter and round in shape.
      To examine the prepared substrates for chemical sensing purposes, the enhancement
      factors were determined by deposition of para-nitrothiophenol (pNTP) on the Ag-NP
      substrates produced by this surface-controlled electroless deposition method.
      Results indicated that the surface of the newly formed Ag-NPs actively interacted
      with pNTP, and the enhancement factors obtained ranged from 50 to 150.

PMID- 20149285
TI  - Optical parameters of vegetable oil studied by terahertz time-domain
      spectroscopy.
AB  - The terahertz time-domain spectra (THz-TDS) of four kinds of vegetable oils were
      measured in the frequency range extending from 0.2 to 1.5 THz. An iterative
      algorithm is employed to determine the parameter extraction for terahertz time
      domain spectroscopy. The terahertz absorption spectra and refractive indices of
      four kinds of vegetable oils were analyzed. Compared with the existing data
      extraction algorithms, the novel iterative algorithm further enhances the
      accuracy of the parameter extraction for terahertz time-domain spectroscopy.

PMID- 20149286
TI  - An intermolecular single-quantum coherence detection scheme for high-resolution
      two-dimensional J-resolved spectroscopy in inhomogeneous fields.
AB  - A new pulse sequence based on intermolecular single-quantum coherences (iSQCs) is
      proposed to achieve high-resolution two-dimensional (2D) J-resolved spectra in
      inhomogeneous fields via three-dimensional (3D) acquisition. Since the iSQC
      evolution period and spin echo evolution period in this sequence are
      intrinsically insensitive to magnetic field inhomogeneities, high-resolution 2D J
      resolved spectra can be recovered from nuclei in inhomogeneous fields by
      projecting the 3D data onto the 2D plane. Analytical expressions of the resulting
      signals were derived assuming the secular dipole-dipole interaction. Analyses of
      a solution sample placed in a deliberately unshimmed magnetic field and of a
      biological sample with intrinsic field inhomogeneities were performed. The
      results show that this sequence provides an attractive and efficient way to
      eliminate the influence of field inhomogeneities on 2D J-resolved spectra, which
      is potentially useful for characterizing complex chemical materials and studying
      biological metabolites in inhomogeneous fields.

PMID- 20149287
TI  - A red-emitting phosphor and its luminescent properties.
AB  - Under 616 nm monitoring, excitation peaks at 395, 465, and 535 nm were observed
      for the red-emitting phosphor Li(0.3)Y(0.82)Mo(0.1)W(0.9)O(4+delta): 0.08Eu(3+)
      (LYMW), which was synthesized using the solid-state method. Particularly in the
      range of 250 to 420 nm, excited peaks can be assigned to the transitions of O(2-)
      ->Mo(6+)/W(6+)/Eu(3+) and four sharp peaks can be assigned to the 4f-4f
      transition of Eu(3+) (approximately 360 nm from the (7)F(0)-->(5)D(4) transition,
      approximately 380 nm from the (7)F(0)-->(5)L(7) transition, approximately 395 nm
      from the (7)F(0)-->(5)(L6) transition, and approximately 415 nm from the (7)F(0)-
      >(5)D(3) transition).

PMID- 20149289
TI  - Human toxocariasis: diagnosis, worldwide seroprevalences and clinical expression
      of the systemic and ocular forms.
AB  - Although human toxocariasis ranks among the most common zoonotic infections
      worldwide, it remains relatively unknown to the public. The causal agents are the
      nematode parasites Toxocara canis and T. cati, whose definitive hosts are dogs
      and cats, respectively. When embryonated eggs are accidentally ingested by
      humans, larvae hatch in the small intestine, penetrate the intestinal wall and
      migrate, via the bloodstream, to the liver, lungs, muscles, eye and central
      nervous system. Although most human infections are asymptomatic, two well-defined
      clinical syndromes are classically recognised: visceral larva migrans (a systemic
      disease caused by larval migration through major organs) and ocular larva migrans
      (a disease limited to the eyes and optic nerves). Two less-severe syndromes have
      recently been described, one mainly in children (covert toxocariasis) and the
      other mainly in adults (common toxocariasis). Here, the current laboratory
      diagnosis, epidemiology and main clinical features of both the systemic and
      ocular forms of human toxocariasis are reviewed. New developments in serological
      diagnosis are described, the available seroprevalence data are analysed, and the
      results of relevant clinical studies that have been published over the last
      decade are explored, to provide an updated overview of this neglected but highly
      prevalent human infection.

PMID- 20149290
TI  - Genetic diversity of Plasmodium falciparum in Bolifamba, on the slopes of Mount
      Cameroon: influence of MSP1 allelic variants on symptomatic malaria and anaemia.
AB  - The influence of the genetic diversity of Plasmodium falciparum infection on the
      clinical presentation of human malaria was investigated in rural Bolifamba,
      Cameroon. Parasite DNA was obtained from the blood of 208 children (aged 1-15
      years) with malarial infection. The prevalences of anaemia and symptomatic and
      asymptomatic malaria among these children were 57.7%, 51.4% and 48.6%,
      respectively. The frequencies of parasites carrying each of the block-2 allelic
      variants (MAD20, K1 and RO33) of merozoite surface protein 1 (MSP1) were compared
      among the symptomatic and asymptomatic cases of malaria, the anaemic and non
      anaemic subjects, and in various age groupings. Although all three allelic
      variants were found in Bolifamba, 32.7% of the children investigated were co
      infected with parasites carrying the RO33 and K1 variants. There was a
      significant difference in the prevalence of each MSP1 allelic variant both
      between age-groups and between the various categories of anaemia considered
      (P<0.0001 for each), with the highest number of alleles occurring in the children
      with severe anaemia. The combination of RO33/K1 co-infection and anaemia was
      detected in most (57.7%) of the children aged 3-<6 years. The RO33/K1 co
      infection was also strongly associated with both fever and high levels of
      parasitaemia (P<0.0001 for each). Although the children of Bolifamba are exposed
      to all three allelic variants of MSP1, which occur either singly or in varying
      combinations in the infected children, RO33/K1 co-infections are particularly
      associated with fever and this association appears independent of age and
      parasite density. The preliminary data presented here should facilitate the
      design of future research towards the development and testing of malaria
      candidate vaccines in the study area.

PMID- 20149291
TI  - The use of remote sensing in the identification of the eco-environmental factors
      associated with the risk of human visceral leishmaniasis (kala-azar) on the
      Gangetic plain, in north-eastern India.
AB  - Human visceral leishmaniasis (VL) or kala-azar remains a major cause of
      mortality, particularly in the developing world. The disease is common in the
      internal regions of north-eastern India, which have a tropical or sub-tropical
      climate. In a recent study on VL in this region, the relationship between the
      incidence of VL and certain physio-environmental factors was explored, using a
      combination of a geographical information system (GIS), satellite imagery and
      data collected 'on the ground'. Some eco-environmental parameters were then used
      to map and describe the spatial heterogeneity seen in the transmission of the
      parasite (Leishmania donovani) that causes VL in India, and to identify those
      habitats, on the Gangetic plain, where the sandfly vectors might thrive. It was
      found that the presence of waterbodies, woodland and urban, built-up areas, soil
      of the fluvisol type, air temperatures of 25.0-27.5 degrees C, relative
      humidities of 66%-75%, and an annual rainfall of 100-<160 cm were all positively
      associated with the incidence of VL. A VL map was created and stratified into
      areas of 'risk' and 'non-risk' for the disease, based on calculations of risk
      indices.

PMID- 20149292
TI  - Seroprevalence of Entamoeba histolytica in the context of HIV and AIDS: the case
      of Vhembe district, in South Africa's Limpopo province.
AB  - In a recent study in northern South Africa, the seroprevalence of Entamoeba
      histolytica infection among 257 HIV-positive and 117 HIV-negative individuals was
      determined, using an ELISA for the detection of antibodies reacting with the
      parasite's galactose/-acetyl-D-galactosamine(Gal/GalNAc)-inhibitable adherence
      lectin. Overall, 34.0% of the 374 participants (36.1% of the females and 28.1% of
      the males) were found seropositive for E. histolytica. Although all age-groups
      were affected by the amoebic pathogen, the subjects aged 50-59 years had the
      highest seroprevalence (69.2%). The seroprevalence of E. histolytica was also
      significantly higher among the HIV-positive subjects than among the HIV-negative
      (42.8% v. 14.5%; chi(2)=28.65; P<0.0001). Among the HIV-positive subjects, those
      with fewer than 200 CD4+ cells/microl were relatively more likely to be
      seropositive for E. histolytica (60.3% v. 43.8%; chi(2)=4.016; P=0.045). This is
      the first report indicating a positive association between E. histolytica
      infection and HIV in South Africa. Further studies, for example to determine the
      occurrence of diarrhoea or liver abscess in the study area, in relation to
      seropositivity for E. histolytica and/or HIV, are now needed.

PMID- 20149293
TI  - Specific PCR-based assays for the identification of Fasciola species: their
      development, evaluation and potential usefulness in prevalence surveys.
AB  - Among the helminths infecting ruminants in China are three taxa belonging to the
      genus Fasciola: F. hepatica, F. gigantica and the so-called 'intermediate form'
      that appears to lie between these two species. Based on the sequences of the
      second internal-transcribed spacers (ITS-2) within the parasites' nuclear
      ribosomal DNA (rDNA), a pair of primers (DSJf/DSJ3) specific for F. hepatica and
      a pair (DSJf/DSJ4) specific for F. gigantica were designed and used to develop
      PCR-based assays. These assays allowed the identification and differentiation of
      F. hepatica, F. gigantica and the 'intermediate' Fasciola, with no amplicons
      produced from heterologous DNA samples. The results of sequencing confirmed the
      species-specific identity of the amplified products. The assays showed good
      sensitivity, giving positive results with as little as 0.11 ng of F. hepatica DNA
      and 0.35 ng of F. gigantica DNA. This meant that the DNA from a single Fasciola
      egg or a single infected snail was sufficient for identification of the Fasciola
      taxon. The developed PCR assays could provide useful tools for the detection,
      identification and epidemiological investigation of Fasciola infection in humans,
      other mammals and snails.

PMID- 20149294
TI  - Seroprevalence of Toxocara canis infection among children in Swaziland, southern
      Africa.
AB  - As there appeared to be no data available on Toxocara canis infection in the
      children of Swaziland, a serological survey of T. canis infection was recently
      conducted among 92 children aged 3-12 years from rural slums in the low- and
      middle-veld. A child was considered seropositive if, in western blots based on
      the excretory-secretory antigens of larval T. canis, his or her serum gave a
      positive result when diluted 1 : 64. Forty-one (44.6%) of the children were found
      seropositive. There were no statistically significant differences in
      seroprevalence between the 49 boys and 43 girls investigated (46.9% v. 41.8%) or
      between the eight subjects aged 12 years and the 47 aged < or = 5 years (62.5% v.
      38.3%); the corresponding odds ratios were 0.81 (95% confidence interval=0.36
      1.86; P=0.62) and 2.69 (95% confidence interval=0.57-12.62; P=0.20),
      respectively. The 66 subjects from the middleveld were, however, significantly
      more likely to be seropositive than the 26 subjects from the lowveld (54.5% v.
      19.2%; odds ratio=5.04, with a 95% confidence interval of 1.70-14.98; P<0.01). It
      seems likely that T. canis infection is common among the children who live in
      slums in Swaziland, particularly in the country's middleveld, probably as the
      result of poor hygiene and poor sanitation.

PMID- 20149295
TI  - Body composition of HIV-positive patients with pulmonary tuberculosis: a cross
      sectional study in Mwanza, Tanzania.
AB  - To estimate the weight deficit and body composition of cases of pulmonary TB
      (PTB), and assess the roles of HIV and the acute-phase response, a cross
      sectional study was carried out in Tanzania. Weight, body mass index (BMI), arm
      muscle area (AMA), arm fat area (AFA) and the serum concentration of the acute
      phase protein alpha(1)-antichymotrypsin (serum ACT) were evaluated for each of
      532 cases of PTB and 150 'non-TB' controls. On average, the female cases of PTB
      not only weighed 7.8 kg less but also had BMI that were 3.1-kg/m(2) lower, AMA
      that were 14.8-cm(2) lower, and AFA that were 7.6-cm(2) lower than those seen in
      the female subjects without TB. Similarly, on average, the male cases of PTB
      weighed 7.1 kg less and had BMI that were 2.5-kg/m(2) lower, AMA that were 18.8
      cm(2) lower and AFA that were 1.6-cm(2) lower than those seen in the male
      subjects without TB. Although HIV infection was associated with a 1.7-kg lower
      weight and a 0.6-kg/m(2) lower BMI (with deficits in both AMA and AFA) among
      males, it was not associated with any such deficits among the female subjects.
      Elevated serum ACT was found to be a negative predictor of BMI, AMA and AFA,
      partially explaining the effects of the PTB but not those of the HIV. There is
      need for a better understanding of the determinants and effects of loss of fat
      and lean body mass in HIV-positive tuberculosis.

PMID- 20149296
TI  - Further evidence of plasmid-encoded bla-(CTX-M-15) and bla-(TEM-1) genes in
      Lebanese isolates of Salmonella enterica serovar Typhimurium that produce
      extended-spectrum beta-lactamase.

PMID- 20149297
TI  - In vivo MRI stem cell tracking requires balancing of detection limit and cell
      viability.
AB  - Cell-based therapy using adult mesenchymal stem cells (MSCs) has already been the
      subject of clinical trials, but for further development and optimization the
      distribution and integration of the engrafted cells into host tissues have to be
      monitored. Today, for this purpose magnetic resonance imaging (MRI) is the most
      suitable technique, and micron-sized iron oxide particles (MPIOs) used for
      labeling are favorable due to their low detection limit. However, constitutional
      data concerning labeling efficiency, cell viability, and function are lacking. We
      demonstrate that cell viability and migratory potential of bone marrow
      mesenchymal stromal cells (BMSCs) are negatively correlated with incorporated
      MPIOs, presumably due to interference with the actin cytoskeleton. Nevertheless,
      labeling of BMSCs with low amounts of MPIOs results in maintained cellular
      function and sufficient contrast for in vivo observation of single cells by MRI
      in a rat glioma model. Conclusively, though careful titration is indicated, MPIOs
      are a promising tool for in vivo cell tracking and evaluation of cell-based
      therapies.

PMID- 20149298
TI  - Refractory angina cell therapy (ReACT) involving autologous bone marrow cells in
      patients without left ventricular dysfunction: a possible role for monocytes.
AB  - Autologous bone marrow mononuclear cell (BMMC) transplantation has emerged as a
      potential therapeutic option for refractory angina patients. Previous studies
      have shown conflicting myocardium reperfusion results. The present study
      evaluated safety and efficacy of CellPraxis Refractory Angina Cell Therapy
      Protocol (ReACT), in which a specific BMMC formulation was administered as the
      sole therapy for these patients. The phase I/IIa noncontrolled, open label,
      clinical trial, involved eight patients with refractory angina and viable
      ischemic myocardium, without left ventricular dysfunction and who were not
      suitable for conventional myocardial revascularization. ReACT is a surgical
      procedure involving a single series of multiple injections (40-90 injections, 0.2
      ml each) into ischemic areas of the left ventricle. Primary endpoints were
      Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at 18
      months follow-up and myocardium ischemic area reduction (assessed by
      scintigraphic analysis) at 12 months follow-up, in correlation with a specific
      BMMC formulation. Almost all patients presented progressive improvement in angina
      classification beginning 3 months (p = 0.008) postprocedure, which was sustained
      at 18 months follow-up (p = 0.004), as well as objective myocardium ischemic area
      reduction at 12 months (decrease of 84.4%, p < 0.004). A positive correlation was
      found between monocyte concentration and CCSAC improvement (r = -0.759, p <
      0.05). Improvement in CCSAC, followed by correlated reduction in scintigraphic
      myocardium ischemic area, strongly suggests neoangiogenesis as the main stem cell
      action mechanism. The significant correlation between number of monocytes and
      improvement strongly supports a cell-related effect of ReACT. ReACT appeared safe
      and effective.

PMID- 20149300
TI  - Islet isolation from juvenile porcine pancreas after 24-h hypothermic machine
      perfusion preservation.
AB  - Pancreas procurement for islet isolation and transplantation is limited by
      concerns for the detrimental effects of postmortem ischemia. Hypothermic machine
      perfusion (HMP) preservation technology has had a major impact in circumventing
      ischemic injury in clinical kidney transplantation and is applied here to the
      preservation and procurement of viable islets after hypothermic perfusion
      preservation of porcine pancreata because pigs are now considered the donor
      species of choice for xenogeneic islet transplantation. Pancreases were
      surgically removed from young (<6 months) domestic Yorkshire pigs (25-32 kg),
      either before or after 30 min of warm ischemia time (WIT), and cannulated for
      perfusion. Each pancreas was assigned to one of six preservation treatment
      groups: fresh controls-processed immediately (cold ischemia <1 h) (G1, n = 7);
      static cold storage-flushed with cold UW-Viaspan and stored in UW-Viaspan at 2-4
      degrees C for 24 h with no prior WIT (G2, n = 9); HMP perfused on a LifePort(R)
      machine at 4-6 degrees C and low pressure (10 mmHg) for 24 h with either KPS1
      solution (G3, n = 7) or Unisol-UHK (G4, n = 7). Additional treatment groups to
      evaluate the effects of prior warm ischemia examined islet isolation after 30 min
      WIT in situ without (G5, n = 6) or with subsequent 24-h HMP with KPS1 (G6, n =
      7). The pancreas was intraductally distended with Liberase PI enzyme and
      normothermically digested. The isolated islets were purified by a continuous
      density-gradient centrifugation. Perfusion-induced glandular edema was G3 = 138
      +/- 19%, G4 = 160 +/- 16%, and G6 = 127 +/- 22%. Islet yield (IEQ/g of pancreas)
      varied between the groups: G1 = 1,425 +/- 610, G2 = 1,002 +/- 262, G3 = 2,242 +/-
      449 (p < 0.05 vs. G2), G4 = 1,901 +/- 420 (p < 0.05 vs. G2), G5 = 1,756 +/- 329,
      and G6 = 1,396 +/- 243. Islet stimulation indices were equivalent between the
      groups and similar to controls (G1). Insulin content (ng/IE) was different
      between the treatment groups with the highest insulin content in islets harvested
      from HMP pancreata. Dithizone staining for islets consistently showed more
      uniform digestion of the perfused organs, with greater separation of the tissue,
      less entrapped islets, and higher islet yield and purity. The salutary effects of
      HMP for 24 h were also manifest after 30-min prior warm ischemia. We conclude
      that 24 h of HMP is well tolerated, leading to moderate edema but no loss of
      function of the harvested islets. The edema appears to aid in enzymatic
      digestion, producing a greater yield and purity of islets compared with pancreas
      subjected to 24 h of static cold storage.

PMID- 20149301
TI  - Humanized culture medium for clinical expansion of human erythroblasts.
AB  - Ex vivo-generated erythroblasts represent alternative transfusion products.
      However, inclusion of bovine components in media used for their growth precludes
      clinical use, highlighting the importance of developing culture media based on
      pharmaceutical grade reagents. In addition, because adult blood generates ex vivo
      lower numbers of erythroblasts than cord blood, cord blood has been proposed as
      the source of choice for ex vivo erythroblast production. To clarify the
      potential of adult blood to generate erythroblasts ex vivo, experiments were
      designed to identify growth factors [stem cell factor (SCF), interleukin-3 (IL
      3), erythropoietin (EPO), and/or thrombopoietin (TPO)] and the optimal
      concentration and addition schedule of hormones (dexamethasone and estradiol)
      sustaining maximal erythroid amplification from adult blood mononuclear cells
      (MNC) using media with serum previously defined as human erythroid massive
      amplification culture (HEMA(ser)). Adult MNC stimulated with SCF and IL-3 in
      combination with EPO generated a 6-12-fold increase in erythroid cells while TPO
      was ineffective. Dexamethasone and estradiol (both at 10(-6) M) exerted partially
      overlapping but nonredundant functions. Dexamethasone was indispensable in the
      first 10 days of culture while estradiol was required from day 10 on. The growth
      factor and hormone combinations identified in HEMA(ser) were then used to
      formulate a media composed of dialyzed pharmaceutical grade human albumin, human
      albumin-lipid liposomes, and iron-saturated recombinant human tranferrin
      (HEMA(def)). HEMA(def) sustained erythroid amplification as efficiently as
      HEMA(ser) for cord blood MNC and 10-fold higher than HEMA(ser) for adult blood
      MNC. In fact, the numbers of erythroblasts generated in HEMA(def) by adult MNC
      were similar to those generated by cord blood MNC. In conclusion, this study
      identifies growth factors, hormone combinations, and human protein-based media
      that allow similar levels of ex vivo erythroid expansion from adult and cord
      blood MNC, paving the way to evaluate adult blood as a source of ex vivo-expanded
      erythroblasts for transfusion.

PMID- 20149302
TI  - Ultrasound imaging for the rheumatologist. XXIV. Sonographic evaluation of wrist
      and hand joint and tendon involvement in systemic lupus erythematosus.
AB  - Systemic lupus erhthematosus (SLE) is an autoimmune multisystem disorder
      characterised by frequent musculoskeletal manifestations. Joint involvement in
      SLE is usually not erosive or destructive but some patients develop hand erosive
      arthritis or deforming arthropathy of the hand (respectively "rhupus" hand and
      Jaccoud arthritis). To date, few studies, evaluated joint and tendon involvement
      in SLE patients by US. We studied wrist and hand structure, using ultrasound, in
      50 patients affected by SLE, detecting inflammatory joint involvement in 80% of
      them at the wrist and in 50% at the hand. Tenosynovitis was visualised in 14
      patients, while structural damage was present in 12% of the SLE group. Those
      results reinforce the importance of including musculoskeletal ultrasound in the
      patient assessment, especially in those cases in which physical examination is
      not conclusive.

PMID- 20149303
TI  - Rare coexistence of gouty and septic arthritis: a report of 14 cases.
AB  - OBJECTIVES: To analyse the characteristic features of patients with coexistence
      of gouty arthritis and pyarthrosis at our university hospital in southern Taiwan,
      an area with high prevalence of hyperuricemia and gout. METHODS: A retrospective
      chart review was performed for patients who had concomitant gouty and septic
      arthritis from July 1998 to June 2008. Clinical and laboratory data of these
      patients were analysed. Furthermore, a comparison was made with published cases
      in English literature. RESULTS: Fourteen cases with coexistence of gouty
      arthritis and pyarthrosis have been identified during the past 10 years. There
      were 13 male and 1 female, all of Han Chinese in ethnicity, with ages ranging
      from 45 to 85 and an average of 63.7 years. At disease presentation, there were
      11 oligoarticular cases (78.6%), 2 monoarticular cases (14.3%) and 1
      polyarticular case (7.1%). Ankle and knee joints were most commonly involved.
      Bacteriological analyses demonstrated gram-positive cocci in 12 cases, of these
      10 were oxacillin-sensitive Staphylococcus aureus (71.4%). Multiple tophi
      deposition was noted in 13 patients (92.9%) and among them 11 patients (84.6%)
      had associated chronic kidney disease. CONCLUSION: Different clinical
      presentations and bacteriological characteristics have been identified in the
      present series. While the mechanisms responsible for such a coexistence remain to
      be elucidated, these cases underline the importance of thorough evaluation of the
      aspirated synovial fluid. Our report adds a novel insight into the understanding
      of the clinical and microbiological manifestations of such a rare concurrence of
      gouty and septic arthritis.

PMID- 20149304
TI  - Patient and physician perception of the infusion process of the biologic agents
      abatacept, infliximab, and rituximab for the treatment of rheumatoid arthritis.
AB  - OBJECTIVES: To assess the process related to each infusible biologic used in
      rheumatoid arthritis (RA) with regard to patient and physician engagement in the
      infusion process, ancillary services required, and participant preferences.
      METHODS: This was a cross-sectional survey of patients with RA and their
      physicians. Biologic-naive patients with RA starting abatacept, infliximab, or
      rituximab were included. Both patients and physicians completed detailed
      questionnaires related to the infusion and satisfaction with the process.
      RESULTS: A total of 205 patients were enrolled: abatacept (n=102), infliximab
      (n=74), rituximab (n=29). Patients were primarily female (75%), Caucasian (85%),
      with a mean age of 58 years. Patients had a mean disease duration of
      approximately 8 years and had typically failed multiple DMARDs. Rituximab
      required the most pre-infusion preparation and the longest infusion time.
      Abatacept was associated with a shorter mean infusion time (42 minutes) than
      infliximab (131 minutes; p<0.0001) or rituximab (274 minutes; p<0.0001) and
      required less time away from work/home (p=0.01 and p<0.0001, respectively).
      Abatacept patients reported significantly less discomfort than rituximab patients
      (p=0.03), while discomfort was similar between abatacept and infliximab. From the
      physicians' perspective, compared to infliximab and rituximab abatacept was very
      easy to administer (57% vs. 27% and 5%, respectively), caused no pain/discomfort
      (52% vs. 42% and 31%), and had very infrequent infusion reactions (75% vs. 30%
      and 44%). CONCLUSION: The process involved in infusion administration, as
      perceived by both the patient and physician, seems to differ across the three
      infusible biologic agents and may have an impact on the decision-making process
      regarding which infusible biologic to use.

PMID- 20149305
TI  - Comparison of the 1999 Sapporo and 2006 revised criteria for the classification
      of the antiphospholipid syndrome.
AB  - OBJECTIVES: The 2006 revised criteria for antiphospholipid syndrome (APS) provide
      a new classification challenge, and studies validating the updated criteria
      against the older ones are still scanty. We compared the 1999 preliminary with
      the 2006 revised classification criteria for APS, and evaluated if the revised
      criteria provide an added value over the original ones. METHODS: A laboratory
      based registry population was obtained on the basis of the positivity of
      antiphospholipid (aPL) antibodies. Patients were analysed for fulfillment of the
      1999 and 2006 classification criteria for APS, non-criteria features of APS, and
      autoantibody profile. RESULTS: Of 144 aPL-positive identified patients, 119 had
      at least 2 aPL tests on separated occasions, and were included in this study.
      According to the 1999 criteria, 23 patients had APS (15 had thrombosis alone, 4
      pregnancy morbidity, and 4 both); while 26 fulfilled the 2006 revised criteria
      (15 had thrombosis alone, 5 pregnancy morbidity, and 6 both). One patient with
      isolated thrombosis who met 1999 criteria did not meet those of 2006 (aCL
      positivity but not >12 weeks apart). One patient with thrombosis, other with
      pregnancy morbidity, and 2 with both only fulfilled the 2006 criteria because
      they had isolated anti-Beta(2)GPI antibody-positivity. High concordance between
      criteria was found, with kappa index of 0.87 (95%; CI, 0.76-0.98). CONCLUSIONS:
      The 2006 revised criteria represent a step-forward since it allows the inclusion
      of patients with anti-Beta(2)GPI antibodies as an isolated serological feature.
      However, a wider time interval between serologic tests seems unlikely to make
      differences.

PMID- 20149307
TI  - High rates of stopping or switching biological medications in veterans with
      rheumatoid arthritis.
AB  - OBJECTIVES: To define the characteristics of a population of veterans with
      rheumatoid arthritis (RA) who have stopped or switched their first biologic
      agent, and to assess if measures of disease activity are predictors in the
      decision to alter the regimen. METHODS: A retrospective analysis of the VA
      electronic medical record system identified RA patient demographic and disease
      activity parameters from 1999 to 2007. Demographic data included age,
      race/ethnicity, sex, and tobacco use. Disease-specific data included date of RA
      onset, past DMARD therapies, prednisone use, as well as the disease activity
      score (DAS-28) and the health assessment questionnaire (HAQ) at each clinic
      visit. The use of six biologicals (infliximab, etanercept, adalimumab, abatacept,
      rituximab, anakinra) was identified in order to compare those who continued with
      the medication to those discontinuing or switching to another biological.
      Descriptive and parametric statistics were applied to define differences between
      the two groups. RESULTS: Of 454 RA patients identified, 212 have been on a
      biologic agent at one point in time, and 100 patients (47%) had either stopped or
      switched their first biologic agent. Among these 100 patients, the most common
      reasons for stopping or switching a biologic agent were adverse events (in 48%)
      and inefficacy (43%) Adverse events included malignancies (23% of 48 patients),
      rash (23%), infections (18.8%), and cardiac complications (18.8%). When comparing
      the 100 patients versus the 112 that did not stop or switch their first agent,
      the DAS-28 correlated significantly with a change of regimen with an OR 2.1
      (p<0.001). The HAQ score had an OR of 2.0 (p<0.04). CONCLUSION: RA patients who
      continue taking their initial biologic medication have similar age, RA disease
      duration, ethnicity, and smoking status to those requiring switching or
      discontinuation. The DAS28 and HAQ scores significantly correlated with stopping
      or switching of a first biologic agent. Adverse event rates were high and their
      distributions differed in this population compared to previous studies of younger
      Caucasian females.

PMID- 20149308
TI  - Regional review of patients with psoriatic arthritis in secondary care in the
      West Midlands: prevalence, disease activity and eligibility for anti-tumour
      necrosis factor therapy.
AB  - OBJECTIVES: Tumour necrosis factor alpha-blockers (TNF-alpha) are licensed for
      the treatment of psoriatic arthritis (PsA) and their use has been approved by the
      National Institute for Health and Clinical Excellence (NICE) for use in the
      United Kingdom under a set of defined clinical criteria. METHODS: In this out
      patient study we evaluated PsA in rheumatology secondary care clinics in units
      across the West Midlands over a 2-week period, assessing prevalence, disease
      activity and eligibility for anti TNF-alpha treatment as defined by the NICE
      criteria. RESULTS: Of the 1718 forms returned from the 2000 sent (86% response
      rate), 175 patients had PsA (10.2%). Of those, 22 (12.6%) were already on anti
      TNF-alpha treatment. 12 patients were noted to have purely axial disease and as
      per the NICE guidelines should not be assessed under the PsA criteria. A further
      5 patients fulfilled the criteria for treatment with anti TNF-alpha with no
      contraindications. In the region 22 out of 27 patients (81%) with active disease
      were correctly on Anti TNF therapy. In total 27 (15.4%) patients with PsA met the
      NICE criteria for treatment of PsA with anti TNF-alpha therapy. 3 patients had
      previously failed anti TNF-alpha treatment. No patient fulfilling criteria for
      treatment were found to have any contraindications to treatment. CONCLUSION: We
      note the relatively high proportion of PsA patients eligible for treatment with
      anti TNF-alpha blockers in the region (15.4%) compared to the NICE estimate
      (2.4%). This may be in part explained by a selection bias. However, the results
      may have significant implications for healthcare provision given the relatively
      high cost of anti-TNF-alpha agents. We comment on the limitations of such
      criteria and the effective use of regional collaboration for both training and
      audit purposes.

PMID- 20149306
TI  - Non-typhi Salmonella infection in patients with rheumatic diseases on TNF-alpha
      antagonist therapy.
AB  - OBJECTIVES: The morbidity and mortality of patients with rheumatic diseases has
      improved considerably following the use of biologic therapies. However, an
      increase in the frequency of bacterial infections has been observed in patients
      receiving these drugs. In the present study we aimed to establish the incidence
      and clinical manifestations of non-typhi Salmonella infection in a large cohort
      of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due
      to severe rheumatic diseases refractory to conventional therapies. METHODS: The
      rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse
      Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared
      with that observed in a cohort of rheumatoid arthritis (RA) patients from the
      EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who
      were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER
      registry was also compared with that available in a non-RA historic control
      cohort reported in a population from Huesca (Northern Spain). RESULTS: Seventeen
      cases of non-typhi Salmonella infection were observed in the series of patients
      exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella
      in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45
      1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years.
      The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha
      inhibitors compared to those not treated with biological therapies was 2.07 (95%
      CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella
      infections in patients with rheumatic diseases undergoing TNF-alpha antagonist
      therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38
      1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a
      severe systemic infection. CONCLUSION: Incidence of non-typhi Salmonella
      infection is not increased significantly in rheumatic patients undergoing anti
      TNF-alpha therapy when compared with RA patients undergoing conventional DMARD
      therapy or with the general population. Nevertheless, at least 50% of patients on
      TNF-alpha have severe complications once they develop non-typhi Salmonella
      infection. This fact suggests that anti-TNF-alpha therapies may predispose to
      salmonella dissemination rather than to infection.

PMID- 20149309
TI  - Does acute synovitis (pseudogout) occur in patients with chronic pyrophosphate
      arthropathy (pseudo-osteoarthritis)?
AB  - OBJECTIVES: Pyrophosphate arthropathy has been linked to diverse clinical
      subtypes. The two most common are: acute synovitis (pseudogout) and chronic
      pyrophosphate arthropathy ("pseudo-osteoarthritis"). We have conducted a study to
      examine whether these are overlapping syndromes. METHODS: We reviewed all
      synovial fluid (SF) analyses performed in our laboratory from January 1988 to May
      1997 to determine if patterns of SF leukocyte counts and Alizarin red stains in
      patients with repeated samples suggest that some patients were prone to acute
      attacks and some to chronic pyrophosphate arthropathy and whether acute attacks
      superimposed on chronic symptoms were common. Joint x-rays were screened for
      osteoarthritis (OA) and chondrocalcinosis. RESULTS: We identified 67 patients who
      had Calcium pyrophosphate dehydrate (CPPD) in their SF and had more than one SF
      examined (185 SF). We divided the patients into 2 groups. Group A (n=25) had at
      least one SF leukocyte count > than 2000 per mm(3) and group B (n=42) had SF
      leukocyte counts always < than 2000 per mm(3). Chondrocalcinosis detected on x
      ray was more common in group A versus group B, 48% versus 19% (p<0.05, Fisher's
      exact test). OA was mild (grades 0-1) in 39% of group A versus 12.5% of group B
      patients, but the difference between groups was not significant. CPPD crystals
      were not detected in 13.5% SFs previously having CPPD crystals. Alizarin red
      staining for suspected hydroxyapatite was more often 2+ to 3+ in group B (31.6%)
      compared to group A (15.5%; p<0.05, Fisher's exact test). CONCLUSION: Acute
      synovitis and chronic pyrophosphate arthropathy are often two distinctive
      syndromes with some patients never having inflammatory attacks. Acute synovitis
      is more common in patients with chondrocalcinosis while chronic pyrophosphate
      arthropathy is associated with increased alizarin red staining and a trend
      suggestive of increased severity of OA.

PMID- 20149310
TI  - Hypoxia inducible factor-1-alpha (HIF-1alpha) is related to both angiogenesis and
      inflammation in rheumatoid arthritis.
AB  - OBJECTIVES: Despite the important role of the transcription factor HIF-1alpha in
      angiogenesis and inflammation, only a few studies on HIF-1alpha expression have
      been performed in RA patients. The aim of the present study was to identify the
      layer in synovial tissue of RA patients where HIF1a is expressed and to find out
      whether HIF-1alpha expression is related to both angiogenesis and inflammation in
      synovium from RA patients. METHODS: A reproducible staining method for HIF-1alpha
      was developed. HIF-1alpha -positive cells were quantified in synovial tissue from
      patients with RA. As control we used synovial tissue from patients with
      osteoarthritis (OA). The number of HIF-1alpha-positive cells was compared with
      the number of blood vessels present and was correlated with the amount of
      inflammation. The amount of inflammation was determined by counting inflammatory
      cells, by estimating the proliferation marker Ki67 in inflamed tissue, and by
      using a recently published synovitis score which gives an accurate estimate of
      the amount of inflammation present. RESULTS: HIF-1alpha was expressed weakly in
      the lining layer and strongly in the sublining layer in RA synovial tissue. In
      contrast, HIF-1alpha was only weakly expressed in OA synovial tissue. The number
      of HIF-1alpha -positive cells correlated strongly with the number of blood
      vessels in RA synovial tissue and with inflammatory endothelial cell infiltration
      (blood vessels), cell proliferation (Ki67) and the synovitis score. CONCLUSIONS:
      HIF-1alpha expression is strongest in the sub-lining layer of RA synovium and is
      related to both angiogenesis and inflammation in synovium from RA patients. These
      results thus suggest that HIF-1alpha could serve as an important new therapeutic
      target in RA, targeting both angiogenesis and inflammation.

PMID- 20149311
TI  - Calcium/calmodulin-dependent protein kinase II (CaMKII) regulates tumour necrosis
      factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis of fibroblast
      like synovial cells (FLS) by phosphorylation of Akt.
AB  - OBJECTIVE: We tried to determine whether calcium/calmodulin-dependent protein
      kinase II (CaMKII) regulates tumour necrosis factor-related apoptosis inducing
      ligand (TRAIL)-mediated apoptosis of fibroblast-like synovial cells (FLS).
      METHODS: CaMKII expression in FLS was studied by both western blotting and real
      time reverse transcription polymerase chain reaction (RT-PCR). TRAIL-mediated
      apoptosis of FLS was quantified by disruption of mitochondrial transmembrane
      potential (DeltaPsim), Leu-Glu-His-Asp (IETD) ase activity and DNA degradation.
      Involvement of CaMKII and other kinases, including extracellular signal-regulated
      kinase (ERK), p38, c-Jun N-terminal kinase (JNK) and Akt during TRAIL-mediated
      apoptosis of FLS was estimated by the use of specific each kinase chemical
      inhibitor. RESULTS: Predominant expression of delta and gamma isoform of CaMKII,
      especially delta isoform, was determined in cultured FLS. TRAIL rapidly induced
      apoptosis of FLS as well as the phosphorylation of extracellular signal-regulated
      kinase (ERK), p38, c-Jun N-terminal kinase (JNK) and Akt. Chemical kinase
      inhibitor toward CaMKII and Akt significantly augmented TRAIL-mediated apoptosis
      of FLS whereas those toward ERK, p38 and JNK did not. Notably, CaMKII chemical
      inhibitor abrogated TRAIL-induced phosphorylation of Akt. Elevation of Leu-Glu
      His-Asp (IETD) ase activity was associated with the apoptotic phenomena, which
      was almost suppressed by IETD competitive peptides. CONCLUSION: Our results
      suggest a first observation that CaMKII regulates TRAIL-mediated apoptosis of FLS
      through Akt, standing an upstream of caspase-8-dependent cascades. Furthermore,
      CaMKII is suggested to be a new therapeutic target molecule of rheumatoid
      arthritis (RA).

PMID- 20149312
TI  - Anti-TNF therapy of ankylosing spondylitis in clinical practice. Results from the
      Czech national registry ATTRA.
AB  - OBJECTIVES: To estimate efficacy, safety and adherence to therapy of ankylosing
      spondlitis (AS) patients included in the Czech National Registry ATTRA, and to
      look for predictive factors for therapy discontinuation. METHODS: Patients were
      included according to the guidelines of the Czech Society for Rheumatology, which
      involve failure of previous therapy, BASDAI >4, and CRP >10 mg/l. Only patients
      with anti-TNF administered for the first time were analysed. Adherence to therapy
      was evaluated using Kaplan-Meier analysis and results were presented as
      cumulative survival. Comparison with data on patients with rheumatoid arthritis
      (RA) followed in the same registry was made. RESULTS: 310 of AS patients who had
      reached at least 1 year as well as those who discontinued the treatment before
      this time point were analysed. Drug survival was longer in patients with AS than
      in those with RA: 84% vs. 78% and 72% vs. 49% after 1 and 3 years of treatment.
      Significant risk factors for treatment discontinuation were female gender (RR
      2.22, p=0.001) and CRP (RR 1.33, p=0.025). The proportion of patients with BASDAI
      <4 during the treatment period was higher in the etanercept group than in the
      infliximab group (p<0.001). The number of patients fully employed increased in
      the whole group from 48% to 63% after 1 year of treatment. CONCLUSION: Follow-up
      of patients with AS in the national registry shows that it is an effective and
      safe way of treatment with longer adherence to anti-TNF therapy in comparison
      with RA patients.

PMID- 20149313
TI  - Interleukin-6 gene -174 promoter polymorphism is associated with endothelial
      dysfunction but not with disease susceptibility in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine whether the interleukin (IL)6 -174 gene polymorphism may
      influence the development of subclinical atherosclerosis manifested by the
      presence of endothelial dysfunction in RA patients. PATIENTS AND METHODS: 311
      patients (228 [73.3%] women; 243 [78.1%] rheumatoid factor positive) who
      fulfilled the 1987 ACR classification criteria for RA seen at the Rheumatology
      outpatient clinic of Hospital Xeral-Calde, Lugo between March 1996 and December
      2006 and 226 matched controls were included in this study. Between March and
      December 2007, a subgroup of 98 patients randomly selected was assessed for the
      presence of endothelial dysfunction. Patients and controls were genotyped for a
      single biallelic (G/C) nucleotide polymorphism (rs1800795) in the promoter region
      at the position -174 of the IL6 gene using a TaqMan 5' allele discrimination
      assay. RESULTS: No significant differences in the IL6 -174 allele or genotype
      frequency between RA patients and controls were found. However, RA patients
      homozygous for the IL6 -174 GG genotype had more severe endothelial dysfunction
      (flow-mediated endothelium-dependent vasodilatation-FMD%: 4.2 + or - 6.6) than
      those carrying the IL6 -174 GC (FMD%: 6.3 + or - 8.1) or IL6 -174 CC (FMD%: 6.0 +
      or - 3.3) genotypes. In this regard, significant differences were observed when
      FMD% values in RA patients carrying the IL6 -174 GG genotype were compared with
      that observed in those carrying the IL6 -174 GC and the IL6 -174 CC genotypes
      (FMD%: 6.3 + or - 4.6) (p=0.02). CONCLUSIONS: Our results support a role of IL6 
      174 gene polymorphism in the development of subclinical atherosclerosis in
      patients with RA.

PMID- 20149314
TI  - Validation of a new screening strategy for anti-extractable nuclear antigen
      antibodies.
AB  - OBJECTIVE: Although indirect immunofluorescence (IIF) is the most widely applied
      screening test for antinuclear antibodies (ANA), it lacks specificity for the
      identification of specific diseases or antigen reactivities. The aim of the
      present study was to validate an anti-extractable nuclear antigen (ENA) screening
      strategy encompassing a three-step cascade whereby an ELISA with pooled specific
      ENA is positioned between the IIF and the final anti-ENA identification. METHODS:
      Sera from 4 populations were tested for anti-ENA using an automated ELISA (EliA
      Symphony) and a line immunoassay (INNO-LIA ANA update). RESULTS: At the
      manufacturer's cut-off, a 96% sensitivity (95% CI 94%-98%) and 96% specificity
      (95% CI 94%-98%) of EliA Symphony for anti-ENA was obtained in a consecutive
      selection of 328 IIF positive serum samples referred for ANA testing. In
      addition, a high sensitivity was demonstrated for anti-ENA reactivities in
      patients with SLE (99%, 95% CI 97%-101%) and SSc (100%), and for anti-ENA
      monoreactivities. CONCLUSION: The EliA Symphony test was shown to be a sensitive
      second-line screening test for anti-ENA antibodies. In the context of a high
      clinical suspicion of connective tissue disease or autoreactivities not included
      in the EliA Symphony assay, third-line testing may be useful, even if the anti
      ENA screening is negative.

PMID- 20149315
TI  - The radiological assessment of axial involvement in psoriatic arthritis: a
      validation study of the BASRI total and the modified SASSS scoring methods.
AB  - OBJECTIVES: To assess the validity of the BASRI and m-SASSS scores for the
      radiological axial involvement in psoriatic arthritis (PsA). Secondary end-points
      were to report on clinical, functional and radiographic characteristics of axial
      involvement. METHODS: Inclusion criteria were satisfaction of the CASPAR criteria
      and the presence of clinical, functional and/or radiological axial involvement.
      Three observers scored the radiographs by BASRI and m-SASSS. The construct
      validity was assessed by examining the correlation of instruments with patient
      reported outcomes and anthropometric measures. The reliability and the
      feasibility of the scores were also considered. RESULTS: Seventy-seven patients
      were enrolled (58 M, 19 F, mean age 49.4 + or - 10.8 yrs, disease duration 13.9 +
      or - 7.9 yrs). Both instruments showed some modest but significant correlation
      with clinical measures. When compared, the BASRI showed a correlation with BASMI
      (rho=0.47, p<0.001), cervical rotation (rho=-0.49, p<0.001), tragus to wall
      (rho=0.34, p<0.01) and occiput to wall (rho=0.49, p<0.001), modified Schober test
      (rho=-0.24, p<0.05) and RLDQ (rho=-0.24, p<0.05). When compared, m-SASSS showed a
      correlation with BASMI (rho=0.39, p<0.001), cervical rotation (rho=-0.41,
      p<0.001), tragus to wall (rho=0.31, p<0.01) and occiput to wall (rho=0.42,
      p<0.001), modified Schober and Schober test (rho=-0.34, p<0.001; rho= -0.32,
      p<0.01), finger to floor (rho=0.37, p<0.01). No correlation was found with BASFI,
      BASDAI and HAQ. Test-retest showed a good reliability of the scores. Both were
      feasible but BASRI was the quickest. CONCLUSION: Our results showed that BASRI
      and m-SASSS were valid instruments for use in spondylitis associated with
      psoriatic arthritis. Longitudinal data is required to provide sensitivity to
      change of the two scores.

PMID- 20149317
TI  - Rheumatoid cachexia and cardiovascular disease.
AB  - OBJECTIVE: It has been frequently stated that rheumatoid cachexia (RC) associates
      with increased cardiovascular risk; however, no studies to date have investigated
      this. The aim of this study was to investigate the association of RC with
      multiple novel and classical cardiovascular disease (CVD) risk factors and the
      presence of established CVD in rheumatoid arthritis (RA). METHODS: A total of 34
      RA patients with RC (RA+RC) were identified from a database of 400 RA patients
      using published RC criteria and compared to the remaining patients (RA-RC) who
      did not fulfil RC criteria. All patients were assessed for fat and fat-free mass,
      albumin (indicator of catabolism), disease activity/severity, novel and classical
      risk CVD factors and established CVD. RESULTS: Fat-free mass (kg) and albumin
      (g/L) were significantly decreased in RA+RC vs. RA-RC patients: 37.3(33.9-41.6)
      vs. 45.9(41.2-55.5), p<0.001 and 39.6 + or - 6.7 vs. 42.4 + or - 4.9, p=0.001).
      Percent body fat was not significantly different. No significant differences were
      detected in either the classical or novel CVD risk factors, 10-year CVD risk or
      the prevalence of established CVD. CONCLUSIONS: RC does not appear to be
      associated with worse CVD profile in RA patients, but this needs to be confirmed
      in prospective studies.

PMID- 20149316
TI  - Prevalence of chondrocalcinosis in Italian subjects from northeastern Italy. The
      Pro.V.A. (PROgetto Veneto Anziani) study.
AB  - OBJECTIVES: To undertake an epidemiological survey of the prevalence of
      radiological chondrocalcinosis (CC) of the lower limbs in the elderly Italian
      population of the Pro.V.A. study. METHODS: Knee and pelvic basin radiographs were
      performed on 3099 subjects aged 65 and older, residing in the Veneto Region of
      Italy (Rovigo and Camposampiero areas). Two readers independently analysed the
      knee, coxofemoral and pubic symphysis x-rays of a consecutive sample of 1629
      subjects according to Altman. Some laboratory indexes, such as serum parathyroid
      hormone (PTH), vitamin D (vit D), bone alkaline phosphatase (bALP),
      deyidroepiandrosterone (DHEA), urinary CrossLaps (XL), and inflammatory
      biomarkers were evaluated. Quantitative variables were summarised as mean + or -
      standard deviation and qualitative ones as distributions. Unpaired t-test was
      used to compare mean values among groups for normally distributed variables, and
      non-parametric Mann-Whitney test for non normal variables. RESULTS: CC was found
      in 169 (mean age 78.2 + or - 8.0 yrs) out of the 1629 subjects studied (10.4%).
      After adjusting for the sex and age structure of the target population, the
      prevalence was 10.0%. CC was more often observed in women than in men (M: 7.0%;
      F: 12.8%, p=0.0002), and increased in occurrence with age, rising from 7.8% in
      subjects aged 65-74 yrs, to 9.4% in those aged 75-84 yrs, and to 21.1% in
      subjects older than 85 yrs. The knee was the most prevalent location since it was
      affected in 94.1% of all the subjects with CC, in particular the right limb. Knee
      CC was bilateral in 71.7% of the affected patients. The occurrence of rheumatic
      disorders did not differ significantly between the subjects with CC and those
      without (rheumatoid arthritis 0.59% vs. 0.48%, p=ns). CONCLUSIONS: Although the
      detection of CC was limited to few joints with the knee being the most affected
      location, our study confirms the frequent presence of CC at different sites, in
      keeping with the possible role of systemic factors. Articular CC is an age
      related disorder, which could partly explain the prevalence discrepancies
      reported by various studies. The prevalence of CC found in our survey based on
      standardised x-ray reading was high, suggesting that CC could be an
      underdiagnosed disease in the absence of radiographic investigation.

PMID- 20149318
TI  - Citrullinated antigens as C1q-binding and monoclonal rheumatoid factor (mRF)
      binding peptides in synovial fluids from rheumatoid arthritis patients.
AB  - OBJECTIVE: Previous studies have demonstrated that immune complexes (ICs) may be
      involved in the pathogenesis of rheumatoid arthritis (RA). However, autoantigens
      contained in rheumatoid ICs remain to be elucidated. In the present study, we
      investigated whether the peptides captured by C1q and monoclonal rheumatoid
      factor (mRF), presumably associated with ICs, were citrullinated in synovial
      fluids from patients with RA. METHODS: Sixteen rheumatoid arthritis synovial
      fluids (RASFs), 7 osteoarthritis synovial fluids (OASFs), and 20 sera from RA
      patients were used for experiments. ICs were measured using commercially
      available kits based on the C1q-binding (C1q-IC) and mRF-binding (mRF-IC) assays.
      Citrullination of the peptides captured by C1q and mRF was detected by anti
      modified citrulline antibody (Senshu Ab) after chemical modification. RESULTS:
      There was a significant correlation between levels of citrullination of C1q
      binding peptides and those of mRF-binding peptides in RASFs (r=0.77), both of
      which were significantly higher than those in OASFs. No citrullinated Ags
      captured by C1q and mRF were detected in sera from patients with RA. CONCLUSIONS:
      We have demonstrated the presence of citrullinated Ags as C1q- and mRF-binding
      peptides in RASF. We suggest that citrullinated Ags may contribute to the
      pathogenesis of RA through IC formation in the joint.

PMID- 20149319
TI  - Risk factors for gouty dactylitis.
AB  - OBJECTIVE: To investigate the risk factors associated with dactylitis in gout.
      METHODS: The questionnaires of 73 consecutive gouty patients, diagnosed according
      to the ACR criteria, were reviewed. They were consecutively screened for the
      presence of dactylitis. RESULTS: Seven out of 73 (9.6%) patients showed
      dactylitis. They had (1) longer disease duration, (2) a higher number of involved
      joints, (3) higher serum uric acid concentration, (4) more tophi, (5) higher ESR,
      and (6) a higher number of ACR criteria besides crystal identification, than the
      others. By logistic regression, renal stones (OR 13.3, 95% CI 1.1-158.3), upper
      extremity involvement (OR 4.9, 95% CI 1.4-16.6), number of ACR criteria (OR 1.9,
      95% CI 1.1-3.3), and ESR (OR 1.02, 95% CI 1-1.04), significantly predicted
      dactylitis. CONCLUSIONS: Dactylitis is a feature of gout representing an
      indicator of disease severity.

PMID- 20149320
TI  - Induction of psoriatic skin lesions in a patient with rheumatoid arthritis
      treated with rituximab.
AB  - Rituximab is a chimeric monoclonal therapeutic antibody which causes depletion of
      CD20-positive B cells. Apart from its apparent efficacy in the treatment of non
      Hodgkin lymphoma and of several rheumatic diseases, it is associated with adverse
      events including the induction of autoimmune phenomena. We describe here the
      development of psoriatic skin lesions in a patient with rheumatoid arthritis
      after the second course of treatment with rituximab. This report supports the
      hypothesis that autoimmune phenomena may occur by biologic agents and there is a
      link between B-cell depletion and the induction of psoriatic skin lesions, which
      were confirmed histologically. However, further studies are needed in order to
      identify the underlying mechanism, as well as the risk factors associated with
      rituximab-induced psoriatic skin lesions.

PMID- 20149321
TI  - Acute myeloid leukemia after infliximab: a case report.
AB  - Concern has arisen regarding a possible increase in the risk of malignant
      diseases such as lymphoproliferative disorders in a patient taking TNF-alpha
      antagonists for the treatment of chronic inflammatory diseases. The evidence of a
      causal link remains unclear. We report a case of 60-year-old male patient who
      developed acute myeloid leukemia during infliximab therapy for ankylo-sing
      spondylitis.

PMID- 20149322
TI  - Tenofovir-induced osteomalacia.
AB  - We present an HIV-infected woman in whom antiretroviral treatment with tenofovir
      disoproxil fumarate (TDF) induced severe skeletal pain, synovial effusions and
      multiple fractures secondary to a Fanconi syndrome with hypophosphatemia and
      osteomalacia. TDF interferes with the replication of mitochondrial DNA in the
      proximal tubules of the kidney, which can explain the delayed onset of this form
      of renal phosphate loss. Nephrotoxicity had been precipitated by cotreatment with
      lopinavir/r, an HIV protease inhibitor which increases tenofovir serum levels and
      inhibits the tubular multidrug resistance protein 4, which is responsible for the
      efflux of tenofovir from tubular cells.Awareness is needed to link the typically
      prolonged onset of clinical symptoms with TDF exposure and then establish the
      correct diagnosis.

PMID- 20149323
TI  - Septic sacroiliitis: an uncommon septic arthritis.
AB  - Septic sacroiliitis is an uncommon joint infection and the diagnosis is often
      delayed. We present the first case of a septic arthritis of the shoulder and of
      the sacroiliac joint in a woman affected by systemic sclerosis, and we reviewed
      the medical literature since 1997 to 2008 on septic sacroiliitis with a specific
      microbiological diagnosis other than Mycobacteria and Brucella species.Evidence
      shows that antibiotic therapy should be continued until full clinical and
      radiological resolution is achieved.

PMID- 20149325
TI  - Risk and management of liver toxicity during methotrexate treatment in rheumatoid
      and psoriatic arthritis: a systematic review of the literature.
AB  - OBJECTIVES: To systematically review the literature on liver toxicity in
      rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients treated with
      methotrexate (MTX), as an evidence base for generating clinical practice
      recommendations for the management of MTX and the indication for a liver biopsy
      (LB) in case of elevated liver enzymes (LE). METHODS: A systematic literature
      search was carried out in MEDLINE, EMBASE, Cochrane Library and ACR/EULAR meeting
      abstracts. Data on the incidence of elevated LE, subsequent adjustments in MTX
      therapy and the prevalence of fibrosis/cirrhosis in pre-MTX and post-MTX LB were
      pooled. RESULTS: Forty-seven out of 426 identified references were included in
      the systematic review. For RA, the incidence rate of elevated LE in the first
      three years of MTX use was 13/100 patient-years with a cumulative incidence of
      31%. MTX was permanently discontinued in 7%, paused or reduced in 26% and
      continued without any adjustment in 67% of patients with an abnormal test. After
      4 years of MTX use, LB showed in 15.3% of the (unrelated) cases mild fibrosis, in
      1.3% severe fibrosis and in 0.5% cirrhosis, while pre-MTX biopsies showed 9%,
      0.3% and 0.3% abnormalities, respectively. For PsA, evidence is limited.
      Additional studies suggest that cumulative MTX dose and serial LE elevations
      among other risk factors are related to liver pathology. CONCLUSIONS: This review
      suggests that LE elevations during MTX therapy are a frequent but transient
      problem, that serial abnormal LE tests might be associated with liver pathology,
      but that cirrhosis is relatively rare. It is, however, not clear from the
      literature how therapy should be adjusted in case of elevated LE and to what
      extent MTX independently attributes to liver toxicity.

PMID- 20149324
TI  - Rituximab in the treatment of dermatomyositis and other inflammatory myopathies.
      A report of 4 cases and review of the literature.
AB  - OBJECTIVE: Rituximab is an anti-CD20 monoclonal antibody targeting B cells, which
      has been used with success in a wide variety of autoimmune diseases. The
      experience with this drug in patients with inflammatory myopathies (IM),
      nonetheless, is still limited. We review the literature and highlight several
      aspects in relation to therapy with rituximab in IM. METHODS: We performed a
      research in the MEDLINE DATABASE. All cases identified from the literature
      research and cases diagnosed in our Unit were included in the analysis. RESULTS:
      We identified 49 patients with IM treated with rituximab in the review of the
      literature carried out (31 female; 18 male), including our patients.
      Dermatomyositis (DM) was the most common disorder for which rituximab treatment
      was administered (69.4%). The other diseases treated included polymyositis (PM)
      16.3%, antisynthetase syndrome (AS) 8.2%, one case with anti-SRP-syndrome and
      other with juvenile dermatomyositis. The median time to diagnosis was 48 (0.75
      480) months. Sixty-five per cent (65.3%) of patients presented with skin
      manifestations, 89.8% with muscle weakness, 7.3% with arthritis, 16.3% with
      interstitial lung disease, and 7.3% with cardiomyopathy. Seventy-one (71.4%) of
      the patients received only one course of rituximab, 18.4% two courses, 4.1%
      three, 2% four and only 4.1% five. We have observed both among our patients and
      those reported in the literature a high rate of response to rituximab, 75% of our
      patients and 72.5% of those described in the literature showed a good response.
      The median time free of symptoms between two courses was 12 (6-19) months.
      Rituximab was generally well tolerated by all patients, with no serious adverse
      events. Most of the adverse events reported were mainly infections, particularly
      respiratory tract infections. CONCLUSIONS: It is our belief that rituximab may be
      an optimal therapeutic choice for inflammatory myopathies. Nevertheless, there is
      a need for additional studies in order to assess the optimal regimen of treatment
      in the different subsets, as well as the initial dose, combination of treatments
      and re-treatment schedule.

PMID- 20149326
TI  - Macrophage migration inhibitory factor -173 polymorphism and risk of coronary
      alterations in children with Kawasaki disease.
AB  - OBJECTIVE: To investigate the possible relationship between MIF -173 polymorphism
      and susceptibility to, and severity of, Kawasaki disease (KD) in a cohort of
      Italian patients. METHODS: Sixty-nine patients (43 F, 26 M, median age 29 months,
      range 3-135 months) with KD and 60 sex-matched healthy caucasian children were
      genotyped for MIF-173. Typing of the MIF gene -173 G/C was performed by PCR and
      restriction fragment length polymorphism. RESULTS: Eight out of 69 (12%) KD
      children were non-responders: 7 required an additional IVIG infusion, while 1
      received 2 IVIG infusions and then steroid administration. 9/69 (13%) KD children
      developed coronary artery abnormalities (CAA) during the second to fourth week of
      disease, and 4 of them required an additional IVIG infusion. MIF genotyping did
      not show significant differences between patients and controls. KD patients
      carrying a MIF -173*C allele developed CAA more frequently than those without MIF
      (7/9 77.8% vs. 16/60 26.7%, OR 9.6, 95% CI 1.80-21.2, p<0.005). Non-responders
      to a single IVIG infusion carried the MIF -173*C allele more frequently than
      responders (6/8 = 75% vs. 17/61 = 28%, OR 5.1, 95% CI 1.42-22.31 p<0.014). In
      multiple regression analysis, KD patients carrying a MIF -173*C allele were found
      to have an increased risk of coronary involvement (OR 7.7, 95% CI 1.36-16.1,
      p=0.021). CONCLUSIONS: We showed that children carrying the MIF polymorphism 
      173*C had a higher percentage of CAA. A potential relationship between a MIF
      polymorphism and risk of CAA in KD might be considered.

PMID- 20149327
TI  - A Brazilian registry of juvenile dermatomyositis: onset features and
      classification of 189 cases.
AB  - OBJECTIVE: To describe onset features, classification and treatment of juvenile
      dermatomyositis (JDM) and juvenile polymyositis (JPM) from a multicentre
      registry. METHODS: Inclusion criteria were onset age lower than 18 years and a
      diagnosis of any idiopathic inflammatory myopathy (IIM) by attending physician.
      Bohan & Peter (1975) criteria categorisation was established by a scoring
      algorithm to define JDM and JPM based on clinical protocol data. RESULTS: Of the
      189 cases included, 178 were classified as JDM, 9 as JPM (19.8: 1) and 2 did not
      fit the criteria; 6.9% had features of chronic arthritis and connective tissue
      disease overlap. Diagnosis classification agreement occurred in 66.1%. Median
      onset age was 7 years, median follow-up duration was 3.6 years. Malignancy was
      described in 2 (1.1%) cases. Muscle weakness occurred in 95.8%; heliotrope rash
      83.5%; Gottron plaques 83.1%; 92% had at least one abnormal muscle enzyme result.
      Muscle biopsy performed in 74.6% was abnormal in 91.5% and electromyogram
      performed in 39.2% resulted abnormal in 93.2%. Logistic regression analysis was
      done in 66 cases with all parameters assessed and only aldolase resulted
      significant, as independent variable for definite JDM (OR=5.4, 95%CI 1.2-24.4,
      p=0.03). Regarding treatment, 97.9% received steroids; 72% had in addition at
      least one: methotrexate (75.7%), hydroxychloroquine (64.7%), cyclosporine A
      (20.6%), IV immunoglobulin (20.6%), azathioprine (10.3%) or cyclophosphamide
      (9.6%). In this series 24.3% developed calcinosis and mortality rate was 4.2%.
      CONCLUSION: Evaluation of predefined criteria set for a valid diagnosis indicated
      aldolase as the most important parameter associated with definite JDM category.
      In practice, prednisone-methotrexate combination was the most indicated
      treatment.

PMID- 20149328
TI  - A longitudinal follow-up study of physical and psychosocial health in young
      adults with chronic childhood arthritis.
AB  - OBJECTIVE: The aim was to describe physical and psychosocial health status in a
      second follow-up of a cohort of patients with chronic childhood arthritis, to
      compare results from the present study with the first follow-up, and to explore
      the course of physical and psychosocial functioning from baseline. METHODS: At a
      median of 18.3 years after symptom onset 55 patients answered the self
      administered questionnaires Health Assessment Questionnaire Disability Index (HAQ
      DI), Visual Analogue Scales (VAS) of pain, fatigue and illness, and General
      Health Questionnaire (GHQ) 30-item version. Results from the current study were
      compared to first follow-up median 8.7 years after symptom onset, and the course
      of physical and psychosocial function from baseline was discussed. RESULTS: At
      second follow-up, 38% reported HAQ-DI above 0 indicating physical disability, 22%
      had a GHQ-30 score in the clinical range indicating psychiatric distress, and
      fatigue seemed to be an overarching aspect of the health status. Pain was an
      important correlate of physical disability at first and second follow-up. At
      second follow-up psychiatric distress was a significant correlate of pain and
      fatigue, indicating a relation to disease severity. The association between
      psychosocial functioning and chronic family difficulties observed at first follow
      up is not evident at second follow-up. CONCLUSIONS: The favourable physical and
      psychosocial outcome reported at first follow-up seems to persist. However,
      arthritis-related ill-health is still evident in a considerable proportion of the
      patients, indicating a constant impact of the disease on every-day life of the
      individual.

PMID- 20149329
TI  - Methotrexate bioavailability after oral and subcutaneous dministration in
      children with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To compare the bioavailability of oral and subcutaneous methotrexate
      (MTX) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventeen
      JIA patients were administered oral (6.1-22.5 mg/m(2)) or subcutaneous (8.8-28.6
      mg/m(2)) MTX. Blood samples were drawn pre-dose, and at 1, 2, and 4 hours after
      administration. Plasma MTX was determined by high-performance liquid
      chromatography. Non-compartmental pharmacokinetic analysis included the maximum
      concentration of plasma MTX (C(max)) and the area under the plasma concentration
      time curve in the interval of 0-4h (AUC(0-4h)). RESULTS: The slopes of the
      regression lines of the dose-corrected parameters Cmax and AUC(0-4h) plotted
      against the dose were negative for oral administration indicating non-linearity
      in pharmacokinetics, while they did not differ from zero for subcutaneous MTX. In
      two groups dosed orally with < or = 10 or >10 mg/m(2) (the average doses: 7.8 vs.
      13.8 mg/m(2), p<0.002), the C(max) and AUC(0-4h) were comparable (p > or = 0.32).
      In four patients switched from oral to subcutaneous administration of the same
      dose, the bioavailability of oral MTX tended to be 11-15% lower when compared to
      subcutaneous route. CONCLUSION: The differences in the pharmacokinetic measures
      of early systemic exposure between oral and subcutaneous routes support the view
      that lower and saturable intestinal absorption of oral MTX limits its
      bioavailability and efficacy within the range of standard doses used to treat
      children with JIA. In light of this evidence it can be recommended to use
      parenteral route of administration when MTX dose around and above 10-15 mg/m(2)
      is needed to achieve sufficient response.

PMID- 20149330
TI  - Development of sarcoidosis during anti-TNF-alpha treatment: what is the
      mechanism?

PMID- 20149332
TI  - Radiologically significant joint improvement in a patient affected by psoriatic
      arthritis treated with adalimumab.

PMID- 20149333
TI  - A brief course of anti-TNF-alpha therapy can cure recurrent episodes of HLA-B27
      associated severe and refractory heel enthesitis.

PMID- 20149335
TI  - Pregnancy appears difficult to obtain and TNF-alpha blockers cannot always be
      discontinued in women with rheumatic diseases.

PMID- 20149336
TI  - Up-regulated expression of suppressor of cytokine signalling (SOCS) proteins
      mRNAs in peripheral blood mononuclear cells from patients with systemic lupus
      erythematosus.

PMID- 20149337
TI  - [Correlation between active anterior rhinomanometry and nasal endoscopy].
AB  - OBJECTIVE: Nasal permeability is related to functional and anatomical parameters,
      which are objectified by active anterior rhinomanometry (AARNM). The study aims
      to compare alterations visualized through Nasal Endoscopy (NE) with nasal flow
      parameters in AARNM. MATERIAL AND METHODS: We carried out a prospective
      observational study of 45 patients suffering from nasal obstruction and septal
      deviation. They were explored through AARNM and NE, and the deviations were
      classified into anterosuperior and anteroinferior quadrants. The degree of
      agreement between observers and the validity of the diagnostic test was then
      analyzed. RESULTS: A sensitivity of 74.6% and a specificity of 60.5% were
      obtained comparing AARNM and EN globally. CONCLUSION: A reduced flow of the
      expiratory phase is correlated to inferior obstructions observed through NE. In
      the narrow nasal vestibule this correlation is not predictive.

PMID- 20149338
TI  - Comparison of persistent submacular fluid in vitrectomy and scleral buckle
      surgery for macula-involving retinal detachment.
AB  - PURPOSE: To compare the frequency of persistent submacular fluid (SMF) and
      sequential visual outcomes after pars plana vitrectomy (PPV) and scleral buckling
      (SB) in recent-onset macula-involving rhegmatogenous retinal detachment (RD), and
      thus to determine the role of persistent SMF on visual outcome with different
      surgical methods. DESIGN: Observational case series. METHODS: Sixty-one patients
      (61 eyes) who underwent successful PPV (16 patients) or SB (45 patients)
      underwent thorough ophthalmologic examinations including optical coherence
      tomography at 1 month after surgery, as well as every 3 months until SMF
      disappeared. The SB group was divided into 2 groups according to the presence (SB
      SMF+) or absence (SB-SMF-) of persistent SMF at 1 month after surgery.
      Preoperative and postoperative best-corrected visual acuities were compared among
      the different surgical groups and also were analyzed depending on the RD duration
      (acute, symptom duration < or = 7 days; subacute, symptom duration > 7 and < or =
      30 days). RESULTS: Persistent SMF at 1 month after surgery was more frequent in
      the SB group (55.6%) than it was in the PPV group (6.25%; P = .006). The SB-SMF+
      group showed worse postoperative best-corrected visual acuity than the PPV or SB
      SMF- groups at 6 to 12 months after surgery, whereas there were no significant
      differences in the final visual acuity among the groups. This difference in
      visual recovery was not observed in patients with subacute RD. CONCLUSIONS: The
      similar visual recovery patterns seen in the PPV and SB-SMF- groups suggest that
      persistent SMF is a more important prognostic factor than surgical method is in
      the setting of acute onset and successful RD surgery.

PMID- 20149339
TI  - Incidence, ocular manifestations, and survival in children with neuroblastoma: a
      population-based study.
AB  - PURPOSE: To determine the incidence, ophthalmic manifestations, and survival
      among children with neuroblastoma in a defined population. DESIGN: Population
      based retrospective cohort. METHODS: The medical records of all pediatric (<19
      years) residents of Olmsted County, Minnesota, diagnosed with neuroblastoma from
      January 1, 1969, through December 31, 2008, were retrospectively reviewed.
      RESULTS: Fourteen children were diagnosed with neuroblastoma as residents of
      Olmstead County, Minnesota, during the 40-year period, yielding an age- and
      gender-adjusted incidence of 11.8 (95% confidence interval [CI]: 5.6-18.0) per
      million patients <15 years of age. The calculated incidence for patients
      presenting before the age of 5 in this cohort was 1 in 5970 children (95% CI:
      3920-12 580 children). The mean age at diagnosis for the 14 study patients was
      22.5 months (range, 10.4-42.6 months). Six of the 14 (43%; 95% CI: 18%-71%) had
      ocular manifestations, including orbital metastasis in 6 (100%), proptosis and
      ecchymosis in 4 (67%), ptosis in 2 (33%), and strabismus in 1 (17%). The Kaplan
      Meier rate of survival for all 14 children was 57% at 1 year (95% CI: 36%-90%)
      and 50% at 5 years (95% CI: 30%-84%), while the 6 with eye findings had a
      survival rate of 17% at 9 months (95% CI: 3%-100%). CONCLUSIONS: The incidence of
      neuroblastoma in this population was 11.8 per million patients <15 years, with
      ophthalmic involvement observed in 6 of the 14 study patients (43%). Orbital
      metastasis in the 6 children in this cohort was associated with poor prognosis.

PMID- 20149340
TI  - Structural and functional assessment in HIV-infected patients using optical
      coherence tomography and frequency-doubling technology perimetry.
AB  - PURPOSE: To assess retinal nerve fiber layer (RNFL) and macular thickness using
      optical coherence tomography (OCT) on HIV-infected patients without ocular
      manifestations and to correlate these findings with frequency-doubling technology
      perimetry (FDT). DESIGN: Cross-sectional study. METHODS: setting: Single center.
      study population: Seventy-three patients (146 eyes) with clinically normal
      examination classified in 3 groups: group A, HIV-infected patients with CD4 count
      <100 cells/mm(3) for at least 6 months; group B, HIV-infected patients with CD4
      count >100 cells/mm(3) since diagnosis; and group C, HIV-negative control
      subjects. observation procedures: Fast RNFL and fast macula scan strategies on
      Stratus OCT and Humphrey Matrix 24-2 full-threshold program. main outcome
      measures: OCT RNFL and macular thicknesses and FDT indices (mean deviation [MD],
      pattern standard deviation [PSD], and glaucoma hemifield test [GHT]). RESULTS:
      Group A had a significantly thinner average RNFL, temporal outer macula, and
      inferior outer macula thicknesses when compared to groups B and C (P < .05).
      Statistically significant differences were observed in the FDT MD between groups
      A and C (P = .034) and in PSD in group A compared to groups B and C (P = .011).
      Eyes of HIV patients with GHT and PSD results outside normal confidence limits
      had thinner average RNFL thickness measures than eyes with results within normal
      limits in the same group of patients (P < .05). CONCLUSIONS: HIV-infected
      patients with low CD4 count have a significant RNFL and macular thinning.
      Functional loss detected by FDT is related to RNFL thinning in HIV-infected
      patients.

PMID- 20149341
TI  - Ocular signs predictive of tubercular uveitis.
AB  - PURPOSE: To determine ocular signs predictive of tubercular uveitis. DESIGN:
      Retrospective, nonrandomized, comparative interventional case study. METHODS:
      Three hundred eighty-six patients with active uveitis were treated at a tertiary
      care single-center uveitis practice. Uveitis was presumed to be tubercular in
      patients who showed evidence of latent or manifest tuberculosis without any other
      known cause and who did not show recurrence of uveitis after 12 months of
      antitubercular therapy. One hundred eighty-two patients who thus obtained
      clinical diagnoses of presumed tubercular uveitis were enrolled in group A. Two
      hundred four patients with uveitis resulting from a nontubercular cause were
      enrolled in group B. Patients were monitored for the presence of types of keratic
      precipitates (mutton fat or fine), posterior synechiae (broad based or filiform),
      iris nodules, snowballs, snow banking, vasculitis (with or without choroiditis),
      serpiginous-like choroiditis, and other types of posterior uveitis (choroidal
      abscess, retinochoroiditis, or exudative retinal detachment) which were compared
      between the 2 groups. Statistical analysis was carried out at a 5% level of
      significance. The main outcome measures were clinical signs significantly
      associated with tubercular uveitis. RESULTS: Broad-based posterior synechiae,
      retinal vasculitis with or without choroiditis, and serpiginous-like choroiditis
      were seen significantly more commonly in patients with tubercular uveitis.
      Filiform posterior synechiae were more frequent in eyes with nontubercular
      uveitis. CONCLUSIONS: Broad-based posterior synechiae, retinal vasculitis with or
      without choroiditis, and serpiginous-like choroiditis in patients with latent or
      manifest tuberculosis in tuberculosis-endemic areas are suggestive of a
      tubercular cause of uveitis and merit specific treatment.

PMID- 20149342
TI  - Four-year incidence and progression of diabetic retinopathy and macular edema:
      the Los Angeles Latino Eye Study.
AB  - PURPOSE: To estimate the 4-year incidence and progression of diabetic
      retinopathy, macular edema (ME) and clinically significant macular edema (CSME)
      among adult Latinos with diabetes mellitus. DESIGN: A population-based,
      longitudinal study of 4658 self-identified Latinos (primarily Mexican Americans),
      residing in Los Angeles, examined at baseline (2000-2003) and at 4 years (2004
      2008). METHODS: Participants underwent a standardized ophthalmic examination.
      Diabetic retinopathy (DR) and CSME were detected by grading of stereoscopic
      fundus photographs using the modified Airlie House classification scheme. chi(2)
      and trend tests were used to assess differences in incidence when stratifying by
      age and duration of diabetes. RESULTS: The 4-year incidence of DR, ME, and CSME
      was 34.0% (182/535), 5.4% (38/699), and 7.2% (50/699) respectively. Younger
      persons and those with longer duration of diabetes mellitus had a higher
      incidence of DR compared to those who were older and had shorter duration of
      diabetes mellitus. A higher incidence of ME was associated with longer duration
      of diabetes mellitus (P = .004). Worsening/progression of any DR was found in
      38.9% (126/324) and improvement occurred in 14.0% (37/265) of participants.
      Progression from nonproliferative DR (NPDR) to proliferative DR (PDR) and from
      NPDR to PDR with high-risk characteristics occurred in 5.3% and 1.9% of
      participants. CONCLUSIONS: The 4-year incidence and progression of DR and the
      incidence of ME and CSME among Latinos are high compared to non-Hispanic whites.
      These findings support the need to identify and modify risk factors associated
      with these long-term complications.

PMID- 20149344
TI  - Lactobacillus species in supragingival plaque in subjects with hyposalivation.
AB  - The aim of the study was to analyse the frequency of different Lactobacillus
      species in relation to the pH-lowering potential of the plaque. METHODS: Ten
      subjects with radiation-induced hyposalivation (RT group) and 10 subjects with
      primary Sjogren's syndrome (pSS group) and matched controls with normal salivary
      secretion were included. Lactobacillus species were selected from their growth on
      Rogosa agar and identified by PCR and restriction fragment length polymorphism
      using HaeIII and HpaII restriction enzymes. RESULTS: Lactobacilli were isolated
      from 14 subjects (6 RT, 3 pSS, 5 controls). The most prevalent species were
      Lactobacillus fermentum (7 subjects), Lactobacillus casei (7 subjects) and
      Lactobacillus rhamnosus (6 subjects). L. fermentum and L. casei were the most
      prevalent species in anterior sites and L. rhamnosus and L. fermentum in
      posterior sites. In anterior sites, hyposalivated subjects with high
      Lactobacillus counts had an increased plaque acidogenicity compared to those with
      low counts. In posterior sites, subjects with high Lactobacillus counts had a
      lower final pH compared with those with low counts. CONCLUSION: There were large
      intra- and inter-individual variations in frequencies of Lactobacillus species
      and Lactobacillus counts, but no specific species could be related to plaque
      acidogenicity.

PMID- 20149343
TI  - Preimplantation genetic diagnosis for stargardt disease.
AB  - PURPOSE: To report the first use of in vitro fertilization (IVF) and
      preimplantation genetic diagnosis to achieve an unaffected pregnancy in an
      autosomal-recessive retinal dystrophy. DESIGN: Case report. METHODS: An affected
      male with Stargardt disease and his carrier wife underwent IVF. Embryos obtained
      by intracytoplasmic sperm injection underwent single-cell DNA testing via
      polymerase chain reaction and restriction enzyme analysis to detect the presence
      of ABCA4 mutant alleles. Embryos were diagnosed as being either affected by or
      carriers for Stargardt disease. A single carrier embryo was implanted. RESULTS:
      Chorionic villus sampling performed during the first trimester verified that the
      fetus possessed only 1 mutant paternal allele and 1 normal maternal allele, thus
      making her an unaffected carrier of the disease. A healthy, live-born female was
      delivered. CONCLUSION: IVF and preimplantation genetic diagnosis can assist
      couples with an affected spouse and a carrier spouse with recessive retinal
      dystrophies to have an unaffected child.

PMID- 20149345
TI  - CLOCK gene variants associate with sleep duration in two independent populations.
AB  - BACKGROUND: Sleep is an active and complex behavior, yet it has two
      straightforward properties-timing and duration. Clock genes are associated with
      dysfunctional timing of sleep, mood, and obesity disorders, which are commonly
      associated with sleep duration. METHODS: Sleep duration was assessed in Central
      Europe, Estonia, and South Tyrol (n approximately 77,000) with the Munich
      ChronoType Questionnaire. It showed a Gaussian distribution in all investigated
      populations after averaging over a standard workweek and normalization according
      to age and gender. A follow-up, two-stage design, linkage disequilibrium-based
      association study was conducted with subjects from South Tyrol (discovery sample;
      n = 283) and with short (< 7 hours) and long (> 8.5 hours) sleepers from Estonia
      (confirmation sample; n = 1011). One hundred ninety-four single nucleotide
      polymorphism markers covering 19 candidate clock genes were genotyped in the
      discovery sample, and two of the best association signals (analyzed by a linear
      regression model) were investigated in the confirmation sample. RESULTS: Single
      and multi-marker associations were found within a CLOCK gene intronic region
      (rs12649507 and rs11932595). In a meta-analysis between South Tyrol and Estonia
      association signals, rs12649507 (p = .0087) remained significant. Significance
      persisted only for the multiple-marker association signal of the
      rs12649507/rs11932595 haplotype GGAA with long sleep (p = .0015). CONCLUSIONS: We
      report an association between variants of the human CLOCK gene and sleep duration
      in two independent populations. This adds another putative function for CLOCK
      besides its possible involvement in circadian timing, depression, obesity, and
      personality.

PMID- 20149346
TI  - N-methyl-D-aspartic acid receptors on striatal neurons are essential for cocaine
      cue reactivity in mice.
AB  - BACKGROUND: Environmental cues associated with cocaine evoke craving and seeking.
      This process, termed cue reactivity, is a critical element of cocaine addiction.
      Although glutamatergic neurotransmission has been implicated in this effect of
      cocaine, the precise subtype and localization in the brain of the glutamatergic
      receptor critical for cocaine cue reactivity is not well-understood. METHODS: We
      used a conditional N-methyl-D-aspartic acid receptor (NMDAR) knockout mouse whose
      NMDAR gene was deleted by Cre expression restricted to striatal neurons. To
      evaluate the role of NMDAR in cocaine cue reactivity, conditional knockout mice
      and control mice (n = 5-8/group) were conditioned for place preference with
      cocaine (5 and 10 mg/kg SC) for 3 days. Their subsequent place preference was
      examined in a drug-free state. RESULTS: Although control mice developed cocaine
      conditioned place preference, mice deficient for NMDAR on striatal neurons failed
      to develop conditioned place preference. CONCLUSIONS: The NMDAR on striatal
      neurons is essential for the development of cocaine cue reactivity in the place
      conditioning paradigm. Our finding identifies a brain region whose constitutive
      NMDAR level serves as a determinant for susceptibility to this aspect of cocaine
      addiction.

PMID- 20149347
TI  - An arginyl residue in rice UDP-arabinopyranose mutase is required for catalytic
      activity and autoglycosylation.
AB  - Plants use UDP-arabinofuranose (UDP-Araf) to donate Araf residues in the
      biosynthesis of Araf-containing complex carbohydrates. UDP-Araf itself is formed
      from UDP-arabinopyranose (UDP-Arap) by UDP-arabinopyranose mutase (UAM). However,
      the mechanism by which this enzyme catalyzes the interconversion of UDP-Arap and
      UDP-Araf has not been determined. To gain insight into this reaction,
      functionally recombinant rUAMs were reacted with UDP-Glc or UDP-Araf. The
      glycosylated recombinant UAMs were fragmented with trypsin, and the glycopeptides
      formed were then identified and sequenced by LC-MS/MS. The results of these
      experiments, together with site-directed mutagenesis studies, suggest that in
      functional UAMs an arginyl residue is reversibly glycosylated with a single
      glycosyl residue, and that this residue is required for mutase activity. We also
      provide evidence that a DXD motif is required for catalytic activity.

PMID- 20149348
TI  - N,N-Diacetylsialyl chloride--a novel readily accessible sialyl donor in reactions
      with neutral and charged nucleophiles in the absence of a promoter.
AB  - N,N-Diacetylneuraminic acid glycosyl chloride was prepared for the first time and
      made to react with various nucleophiles to give the corresponding alpha-glycosyl
      phosphate, beta-glycosyl dibenzyl phosphate, alpha-glycosyl azide, alpha-phenyl
      thioglycoside and alpha-glycosyl xanthate in 65-82% yields and high
      stereoselectivity while its reactions with simple alcohols were not
      stereoselective. The new sialyl donor made possible the first stereoselective
      synthesis of sialic acid glycosyl phosphate with alpha-configuration and highly
      efficient synthesis of beta-configured sialic acid glycosyl dibenzyl phosphate.

PMID- 20149349
TI  - The structure of the carbohydrate backbone of the lipooligosaccharide from the
      halophilic bacterium Arcobacter halophilus.
AB  - A novel oligosaccharide was isolated and identified from the lipooligosaccharide
      fraction of the halophilic marine bacterium Arcobacter halophilus. The complete
      structure was achieved by chemical analysis, 2D NMR spectroscopy, and MALDI mass
      spectrometry as the following: alpha-Glc-(1-->7)-alpha-Hep-(1-->5)-alpha-Kdo4P-(2
      ->6)-beta-GlcN4P-(1-->6)-alpha-GlcN1P.

PMID- 20149350
TI  - [Chronic pain after inguinal hernia surgery].

PMID- 20149351
TI  - [Delayed anastomotic dehiscence in advanced colorectal cancer treated with
      BevacizumabTM].

PMID- 20149352
TI  - [Outpatient treatment for haemorrhoids with hemorpex. An innovative method?].

PMID- 20149354
TI  - Proximate units in word production: phonological encoding begins with syllables
      in Mandarin Chinese but with segments in English.
AB  - In Mandarin Chinese, speakers benefit from fore-knowledge of what the first
      syllable but not of what the first phonemic segment of a disyllabic word will be
      (Chen, Chen, & Dell, 2002), contrasting with findings in English, Dutch, and
      other Indo-European languages, and challenging the generality of current theories
      of word production. In this article, we extend the evidence for the language
      difference by showing that failure to prepare onsets in Mandarin (Experiment 1)
      applies even to simple monosyllables (Experiments 2-4), and confirm the contrast
      with English for comparable materials (Experiments 5 and 6). We also provide new
      evidence that Mandarin speakers do reliably prepare tonally unspecified
      phonological syllables (Experiment 7). To account for these patterns, we propose
      a language general proximate units principle whereby intentional preparation for
      speech as well as phonological-lexical coordination are grounded at the first
      phonological level below the word at which explicit unit selection occurs. The
      language difference arises because syllables are proximate units in Mandarin
      Chinese, whereas segments are proximate in English and other Indo-European
      languages. The proximate units perspective reconciles the aspiration toward a
      language general account of word production with the reality of substantial cross
      linguistic differences.

PMID- 20149355
TI  - Symbolic and nonsymbolic number comparison in children with and without
      dyscalculia.
AB  - Developmental dyscalculia (DD) is a pervasive difficulty affecting number
      processing and arithmetic. It is encountered in around 6% of school-aged
      children. While previous studies have mainly focused on general cognitive
      functions, the present paper aims to further investigate the hypothesis of a
      specific numerical deficit in dyscalculia. The performance of 10- and 11-year-old
      children with DD characterised by a weakness in arithmetic facts retrieval and
      age-matched control children was compared on various number comparison tasks.
      Participants were asked to compare a quantity presented in either a symbolic
      (Arabic numerals, number words, canonical dots patterns) or a nonsymbolic format
      (noncanonical dots patterns, and random sticks patterns) to the reference
      quantity 5. DD children showed a greater numerical distance effect than control
      children, irrespective of the number format. This favours a deficit in the
      specialised cognitive system underlying the processing of number magnitude in
      children with DD. Results are discussed in terms of access and representation
      deficit hypotheses.

PMID- 20149356
TI  - The simulation of virus life cycle with quantum gates.
AB  - Quantum physics and molecular biology are two disciplines that have evolved
      relatively independently. However, recently a wealth of evidence has demonstrated
      the importance of quantum mechanics for biological systems and thus a new field
      of quantum biology is emerging. There are many claims that quantum mechanics
      plays a key role in the origin and/or operation of biological organisms. We
      consider the nucleonic acid of virus as a quantum system in this paper and
      discuss virus life cycle from the view-point of quantum and simulate it using
      quantum gates for the first time. The maximally entangled states show infected
      cell can change to entire cell, the virus can switch from the lysogenic to the
      lytic and the prophages can remain latent in the bacterial chromosome for many
      generations.

PMID- 20149357
TI  - Magnetic resonance neurography for the diagnosis of extrapelvic sciatic
      endometriosis.
AB  - OBJECTIVE: To illustrate magnetic resonance neurography findings of severe
      sciatic injury and muscle denervation related to deep gluteal endometriosis at
      the sciatic notch. DESIGN: Case report. SETTING: Academic teaching hospital.
      PATIENT(S): A 39-year-old woman with a 4-year history of sciatica related to the
      menstrual cycle. INTERVENTION(S): Surgical exploration of the sciatic notch for
      diagnostic confirmation, external neurolysis of the sciatic nerve, and eventual
      pharmacologic treatment. MAIN OUTCOME MEASURE(S): Magnetic resonance neurography
      imaging revealed severe neuropathic injury and muscle denervation related to a
      deep infiltrative endometriotic focus at the sciatic notch, which was confirmed
      histologically on surgical exploration. Detailed electrodiagnostic and clinical
      neurologic examinations at initial presentation and during follow-up were
      obtained for further assessment of nerve degeneration, muscle denervation, and
      clinical recovery. RESULT(S): Initial gynecologic and eventual laparoscopic
      evaluation on persisting complaints were without pathological findings. When a
      progressive weakness of the leg was noted, magnetic resonance neurography
      revealed a severe axonal damage to the sciatic nerve and denervation of distal
      target muscles related to a diffuse infiltrative lesion at the sciatic notch. On
      surgical exploration, extragenital endometriosis was confirmed histologically.
      Considerable improvement in pain and strength occurred after pharmacologic
      therapy with a GnRH analogue. CONCLUSION(S): This is the first report to describe
      imaging findings of magnetic resonance neurography in severe neuropathic injury
      of the sciatic nerve and subsequent muscle denervation related to a deep
      infiltrative gluteal endometriotic focus.

PMID- 20149359
TI  - The role of autophagy in follicular development and atresia in rat granulosa
      cells.
AB  - OBJECTIVE: To investigate the involvement of autophagy in folliculogenesis and
      its correlation with apoptosis. DESIGN: Animal model-based study. SETTING:
      University medical center. ANIMAL(S): Twenty-one day-old female Sprague-Dawley
      rats. INTERVENTION(S): Ovaries obtained from established immature rat models
      primed with pregnant mare serum gonadotropin (PMSG) were used for the induction
      of follicular development and atresia. Granulosa cells isolated from developing
      follicles were cultured in serum-free condition with or without follicle
      stimulating hormone. MAIN OUTCOME MEASURE(S): Microtubule-associated light-chain
      protein 3 (LC3) and autophagic vacuoles were used as autophagic markers, and
      cleaved caspase-3 was used as an apoptotic marker in ovaries and/or granulosa
      cells. RESULT(S): The LC3 protein was expressed mainly in granulosa cells during
      all developmental stages. In granulosa cells isolated from PMSG-primed immature
      rat ovaries, LC3-II expression showed a similar expression pattern to cleaved
      caspase-3. In addition, granulosa cells of atretic follicles that showed intense
      cleaved caspase-3 staining also showed intense LC3 immunoreactivity. An in vitro
      culture experiment revealed that the levels of LC3-II and cleaved caspase-3
      proteins were gonadotropin-dependent. The induction and the gonadotropin
      dependency of granulosa cell autophagy were confirmed by the observation of
      autophagic vacuoles under transmission electron microscopy. CONCLUSION(S): These
      preliminary results suggest that autophagy is induced mainly in granulosa cells
      during folliculogenesis and shows good correlation with apoptosis.

PMID- 20149358
TI  - Serum inhibin-b in fertile men is strongly correlated with low but not high sperm
      counts: a coordinated study of 1,797 European and US men.
AB  - OBJECTIVE: To describe associations between serum inhibin-b and sperm counts,
      adjusted for effect of time of blood sampling, in larger cohorts than have been
      previously reported. DESIGN: Cross-sectional studies of spermatogenesis markers.
      SETTING: Four European and four US centers. PATIENT(S): Fertile men (1,797) were
      included and examined from October 1996-February 2005. INTERVENTION(S): The study
      was observational and therefore without any intervention. MAIN OUTCOME
      MEASURE(S): Associations between inhibin-b and semen variables controlled for
      time of blood sampling and other covariates. RESULT(S): Inhibin-b decreased about
      2.00% per hour from 8 am-12 pm and then about 3.25% per hour from 12 pm-4 pm.
      There was a strong positive association between inhibin-b levels less than 150
      pg/mL and both sperm concentration and total sperm count (slopes of the
      regression lines were beta=0.011 and beta=0.013 for natural logarithm-transformed
      sperm concentration and total sperm count, respectively). For inhibin-b levels of
      150-300 pg/mL the associations were not as steep (beta=0.002), but still
      significant. For inhibin-b levels more than 300 pg/mL there was little
      association to the sperm counts. Neither sperm motility nor morphology was
      significantly related to inhibin-b level in any group. CONCLUSION(S): Serum
      inhibin-b levels decrease nonlinearly during the daytime, and are positively
      correlated with sperm counts, but the predictive power is best when inhibin-b is
      low.

PMID- 20149360
TI  - Corifollitropin alfa in a long GnRH agonist protocol: proof of concept trial.
AB  - Fifty healthy women, aged 18-39 years with no known risk of ovarian
      hyperstimulation were treated with 100 or 150 MUg corifollitropin alfa (dependent
      on body weight) in a long GnRH agonist protocol. At these doses, corifollitropin
      alfa initiated and supported growth of a large cohort of follicles during the
      first week of ovarian stimulation.

PMID- 20149361
TI  - Failure of the GnRH antagonist ganirelix to block the positive feedback effect of
      exogenous estrogen in normal women.
AB  - This study investigated whether the GnRH antagonist ganirelix is able to block
      the positive-feedback effect of E2 in normal women. Ganirelix was unable to block
      the positive-feedback effect, suggesting that the clinical efficacy of GnRH
      antagonists in IVF cycles is determined by the hyperstimulation process.

PMID- 20149362
TI  - Effect of childhood kidney transplantation on puberty.
AB  - OBJECTIVE: To evaluate sexual and linear growth in kidney transplant (KTX)
      children receiving cyclosporine A, low-dose prednisolone and azathioprine. STUDY
      DESIGN: Prospective case-control study. SETTING: University-affiliated urology
      and nephrology center, obstetric and gynecology departments. PATIENT(S): Eighteen
      girls and 21 boys with successful KTX before the age of 16 years. Controls were
      healthy and age matched (200 girls and 171 boys). INTERVENTION(S): Assessment of
      sexual maturation by Tanner staging and linear growth by height standard
      deviation score (HSDS) and height increment (HI). MAIN OUTCOME MEASURE(S):
      Pubertal age in KTX vs. control, ratios of KTX with normal and retarded sexual
      maturation and linear growth. RESULT(S): Puberty in KTX children was
      significantly delayed compared with controls. Delayed sexual maturation was found
      in 22.2% of girls and 19.1% of boys, and poor HSDS was found in 38.9% of girls
      and 33.3% of boys. Improvement in HSDS was significantly lower in girls compared
      with boys. Improvement in HSDS did not significantly differ in prepubertal vs.
      pubertal children. Prepubertal HI was significantly higher than pubertal HI in
      boys, but not in girls. Significant negative correlation was found between HI,
      duration of immunosuppression, and serum creatinine level. CONCLUSION(S): KTX
      children receiving cyclosporine A, low-dose prednisolone, and azathioprine showed
      acceptable sexual and physical maturation in a majority of cases. Impaired sexual
      and linear growth after receiving KTX is related to poor graft function, post-KTX
      interval, and gender.

PMID- 20149363
TI  - Single and twin ongoing pregnancies in two cases of previous ART failure after
      ICSI performed with sperm sorted using annexin V microbeads.
AB  - OBJECTIVE: To treat couples with intracytoplasmic sperm injection (ICSI) after
      annexin V sperm sorting. DESIGN: Two case reports. SETTING: Department of
      Reproductive Medicine at a private medical institute. PATIENT(S): Couples on
      infertility treatment, donor oocytes. INTERVENTION(S): Sperm sorted with annexin
      V magnetic microbeads before ICSI, day 3 embryo transfer; case 1: ovum donation;
      case 2: patient oocytes. MAIN OUTCOME MEASURE(S): 1) Sperm DNA fragmentation
      (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling [TUNEL])
      and active caspase-3 (immunocytochemistry); 2) fertilization rate, embryonic
      quality, blastocyst development of nontransferred embryos, and pregnancy outcome
      after ICSI of sorted sperm. RESULT(S): Case 1: Premature ovarian failure patient
      with previous fertilization failures: asthenoteratozoospermia, abnormal DNA
      fragmentation (TUNEL 30%; normal <20%). ICSI with annexin V-treated sperm done on
      six donated metaphase II (MII) oocytes; four fertilized, and a 5-cell/grade-2 and
      a 6-cell/grade-2-3 embryo were transfered. A day 5 blastocyst was cryopreserved.
      The patient was in the last trimester of gestation. Case 2: Couple with >4 years
      of primary infertility and recent ICSI failure. Semen with teratozoospermia (5%
      normal forms [Kruger]) and abnormal active caspase-3 (16%; normal <11%). ICSI
      with annexin V-treated sperm done on 9 MII oocytes. All fertilized; a 7
      cell/grade-1 and an 8-cell/grade-1-2 embryo were transferred. A day 5 expanded
      blastocyst was cryopreserved. The patient was in the second trimester of a twin
      normal pregnancy. CONCLUSION(S): Sperm sorting with annexin V columns was
      effective in the treatment of two cases of ICSI failure, resulting in a single
      and a twin pregnancy after transfer of two embryos in each case.

PMID- 20149364
TI  - CD56brightCD16- natural killer cells accumulate in the ovarian follicular fluid
      of patients undergoing in vitro fertilization.
AB  - CD56(bright)CD16(-) natural killer (NK) cells that express CXCR3 accumulate in
      the follicular fluid of patients with a good response to ovarian stimulation. It
      is conceivable that granulosa cells of good responders that express the chemokine
      CXCL10 recruit these NK cells to support follicular angiogenesis.

PMID- 20149365
TI  - The first community-based report on the effect of genital Schistosoma haematobium
      infection on female fertility.
AB  - A cross-sectional study in an Schistosoma haematobium endemic area of rural
      Zimbabwe examined 483 resident women between the ages of 20 and 49 years who were
      interviewed about fertility. S. haematobium ova in genital tissue was found to be
      significantly associated with infertility.

PMID- 20149366
TI  - Antral follicle count: absence of significant midlife decline.
AB  - OBJECTIVE: To examine the conventional wisdom that declines in antral follicle
      count accelerate after approximately 37 years of age, which has influenced
      clinical decision making. We critically examine evidence for this sudden
      acceleration. DESIGN: Cross-sectional study. SETTING: Academic setting.
      PATIENT(S): Two hundred fifty-two white women aged 25 to 45 years with regular
      cycles, a community-based study. INTERVENTION(S): Antral follicle counts were
      measured by transvaginal ultrasound in early follicular phase. MAIN OUTCOME
      MEASURE(S): Determination of the rate of antral follicle count decline with age.
      RESULT(S): The relationship of antral follicle count with age was determined by
      comparing a linear model with four nonlinear models (biphasic, quadratic, spline,
      and power). The linear model estimates the follicle decline as 0.97 follicles per
      year. The biphasic model had estimates of 0.76 follicles per year before 39.6
      years of age and 1.92 follicles per year thereafter. At age 35 years the linear,
      quadratic, broken line, spline, and power models gave estimated declines
      (respectively) of 0.97, 0.94, 0.76, 0.17, and 0.90 follicles per year. At age 43
      years the values were 0.97, 1.51, 1.92, 1.78, and 1.64 follicles per year. The
      quality of model fit was comparable for all models. CONCLUSION(S): Antral
      follicle count decline with age in a white population is best described as a
      gradual acceleration in decline with age. Therefore antral follicle count alone
      should not be used to determine aggressive treatment because of fear of rapid
      loss of follicles.

PMID- 20149367
TI  - Common genetic and environmental factors among craniofacial traits in Belgian
      nuclear families: comparing skeletal and soft-tissue related phenotypes.
AB  - The major objective of this study was to determine the possible effects of common
      genetic and environmental factors among 18 craniofacial anthropometric traits,
      with special attention to the differences between skeletal and soft-tissue
      related phenotypes. The studied sample consisted of 122 nuclear families living
      in Brussels and included 251 males and 258 females aged from 13 to 72 years.
      Univariate and bivariate quantitative genetic analyses were performed using a
      variance components procedure implemented in SOLAR software. All phenotypes were
      significantly influenced by additive genetic factors with heritability estimates
      ranging from 0.46 (nose height) to 0.72 (external biocular breadth). Sex, age and
      their interactions explained 7-46% of the total phenotypic variance of the
      traits. Bivariate analysis revealed that several traits share a common genetic
      and/or environmental basis while other traits show genetic and environmental
      independence from one another. More and greater genetic and environmental
      correlations were observed among skeletal phenotypes, than among soft-tissue
      traits and between both categories. Apart from the tissue composition, other
      characteristics of the craniofacial morphology such as the orientation (e.g.
      heights, breadths) have shown to be important factors in determining pleiotropy
      and common environmental effects between some pairs of traits. In conclusion, the
      results confirm that overall head configuration is largely determined by additive
      genetic effects, and that common genetic and environmental factors affecting
      craniofacial size and shape are stronger for the skeletal traits than for the
      soft-tissue traits.

PMID- 20149368
TI  - Climatic factors in the development of radiographic hand osteoarthritis.
AB  - A study was undertaken to evaluate whether various ethno-territorial samples have
      different characteristics of radiographic hand osteoarthritis (OA) and to
      evaluate whether climate is associated with differences in hand OA
      characteristics. The total sample included 4775 individuals (2220 males and 2555
      females), belonging to 12 sub-samples, including 9 ethnic groups, from 10
      geographic locations in the former USSR. Ethnicity, latitude, longitude, and
      climatic parameters (mean temperatures, humidity, and day length of January and
      July) were collected for each sample. X-rays of the left hand were obtained from
      each individual. Prevalence of hand OA was evaluated in four age groups (36-40,
      41-45, 46-50, and 51-55 years). Using maximum likelihood estimation, the
      following characters were determined: the mean age of persons having 1 and 5
      affected joints--A(m1) and A(m5), and the mean time in which one additional joint
      was affected--T(m). The difference between samples was evaluated using the chi(2)
      test. The associations between hand OA, and climate were evaluated using
      Pearson's correlations. Significant differences in OA characteristics among
      samples were found. Prevalence of hand OA in the age-group 46-50 showed
      significant association with longitude (r=0.57, p=0.05) and inter-seasonal
      temperature amplitude (r=0.77, p=0.0035) and significant negative association
      with mean temperature of January (r=-0.72, p=0.0089). Significant associations
      were found between longitude, the mean temperature of January, and inter-seasonal
      temperature amplitude and age-related hand OA parameters (A(m1) and A(m5)). The
      present study indicates that the differences in characteristics of radiographic
      hand OA among samples are most likely associated with climatic variation.

PMID- 20149369
TI  - High-dose antioxidant administration is associated with a reduction in post
      injury complications in critically ill trauma patients.
AB  - BACKGROUND: We recently demonstrated a high-dose antioxidant (AO) protocol was
      associated with reduction in mortality. The purpose of this study was to evaluate
      the impact of AO on organ dysfunction and infectious complications following
      injury. PATIENTS AND METHODS: High-dose AO protocol: ascorbic acid 1000 mg q 8 h,
      alpha-tocopherol 1000 IU q 8 h, and selenium 200 mcg qd for 7-day course.
      Retrospective cohort study evaluating all patients admitted after protocol
      implementation (AO+), October 1, 2005 to September 30, 2006. Comparison cohort
      (AO-): all patients admitted in the year prior to implementation, October 1, 2004
      to September 30, 2005. RESULTS: 2272 patients included in the AO+ group, 2022
      patients in the AO- group. Demographics and injury severity were similar.
      Abdominal compartment syndrome (ACS) (2.9% vs. 0.7%, <0.001), surgical site
      infections (2.7% vs. 1.3%, p=0.002), pulmonary failure (27.6% vs. 17.4%,
      p<0.001), and ventilator-dependent respiratory failure (10.8% vs. 7.1%, p<0.001)
      were significantly less in the AO+ group. Multivariate regression showed 53% odds
      reduction in abdominal wall complications and 38% odds reduction in respiratory
      failure in the AO+ group. CONCLUSIONS: Implementation of a high-dose AO protocol
      was associated with a reduction in respiratory failure and ventilator-dependence.
      In addition, AO were associated with a marked decrease in abdominal wall
      complications, including ACS and surgical site infections.

PMID- 20149371
TI  - Extended focused assessment with sonography for trauma (EFAST) in the diagnosis
      of pneumothorax: experience at a community based level I trauma center.
AB  - INTRODUCTION: Early identification of pneumothorax is crucial to reduce the
      mortality in critically injured patients. The objective of our study is to
      investigate the utility of surgeon performed extended focused assessment with
      sonography for trauma (EFAST) in the diagnosis of pneumothorax. METHODS: We
      prospectively analysed 204 trauma patients in our level I trauma center over a
      period of 12 (06/2007-05/2008) months in whom EFAST was performed. The patients'
      demographics, type of injury, clinical examination findings (decreased air
      entry), CXR, EFAST and CT scan findings were entered into the data base.
      Sensitivity, specificity, positive (PPV) and negative predictive values (NPV)
      were calculated. RESULTS: Of 204 patients (mean age--43.01+/-19.5 years, sex-
      male 152, female 52) 21 (10.3%) patients had pneumothorax. Of 21 patients who had
      pneumothorax 12 were due to blunt trauma and 9 were due to penetrating trauma.
      The diagnosis of pneumothorax in 204 patients demonstrated the following:
      clinical examination was positive in 17 patients (true positive in 13/21, 62%; 4
      were false positive and 8 were false negative), CXR was positive in 16 (true
      positive in 15/19, 79%; 1 false positive, 4 missed and 2 CXR not performed before
      chest tube) patients and EFAST was positive in 21 patients (20 were true positive
      [95.2%], 1 false positive and 1 false negative). In diagnosing pneumothorax EFAST
      has significantly higher sensitivity compared to the CXR (P=0.02). CONCLUSIONS:
      Surgeon performed trauma room extended FAST is simple and has higher sensitivity
      compared to the chest X-ray and clinical examination in detecting pneumothorax.

PMID- 20149372
TI  - Surgical considerations in the management of combined radiation blast injury
      casualties caused by a radiological dirty bomb.
AB  - The capacity for surgical teams to respond appropriately to the consequences
      caused by the detonation of a radiological dirty bomb will be determined by prior
      knowledge, familiarity and training for this type unique terrorist event. This
      paper will focus on the surgical aspects of this scenario with particular
      emphasis on the management of combined trauma-radiological injury. The paper also
      describes some of the more serious explosion-contamination incidents from nuclear
      industrial sources, summarises learning points and parallels taken from these
      scenarios in relation to subject of a radiological dirty bomb and describes the
      likely radioactive substances involved.

PMID- 20149373
TI  - Peak radial and circumferential strain measured by velocity vector imaging is a
      novel index for detecting vulnerable plaques in a rabbit model of
      atherosclerosis.
AB  - AIMS: To evaluate the reliability of velocity vector imaging (VVI) for detecting
      vulnerable plaques. METHODS AND RESULTS: After aortic balloon injury, 60 rabbits
      were fed a 1% cholesterol diet for 10 weeks and normal chow for another 6 weeks.
      Adenovirus containing p53 or lac Z was then injected into the aortic plaques and
      rabbits were divided into p53-treated group (n=20), lac Z-treated group (n=20)
      and blank control group (n=20). Peak longitudinal (LSp), radial (RSp) and
      circumferential (CSp) strain of plaques was measured using VVI at the end of week
      18 before pharmacological triggering. Higher RSp and CSp and lower LSp were found
      in ruptured than those in non-ruptured plaques, and RSp, CSp and LSp correlated
      well with the fibrous cap thickness and plaque content of macrophages, smooth
      muscle cells and collagen (all p<0.01). A logistic regression model showed that
      both RSp (RR: 8.96, 95% CI: 5.3575-10.4857, p<0.001) and CSp (RR: 8.45, 95% CI:
      5.9043-9.1043, p<0.001) were significant predictors of plaque rupture. RSp and
      CSp had a sensitivity of 88.0% and 88.6% and a specificity of 88.6% and 92.0% to
      predict plaque disruption, respectively. CONCLUSION: VVI offers a new and
      noninvasive technique for measuring the peak strain of atherosclerotic plaques
      and RSp and CSp are a novel index with a high sensitivity and specificity for
      detecting plaques vulnerable to rupture.

PMID- 20149374
TI  - Paraoxonase 1 (PON1) deficiency in mice is associated with reduced expression of
      macrophage SR-BI and consequently the loss of HDL cytoprotection against
      apoptosis.
AB  - BACKGROUND: Paraoxonase 1 (PON1) was shown to stimulate HDL binding and HDL
      mediated cholesterol efflux from macrophages. This study examined the role of
      PON1 in the expression of proteins that enhance macrophage HDL binding, i.e.
      ABCA1 and SR-BI. METHODS AND RESULTS: ABCA1 expression was similar, whereas SR-BI
      expression (mRNA and protein determined by FACS, Western blot, or
      immunocytochemistry) was significantly decreased in peritoneal macrophages from
      PON1 deficient (MPM-PON1(0)) in comparison to C57Bl/6 (MPM-Control) mice. PON1
      deficiency correction with HDL-control, recombinant PON1 (rePON1), or by
      transfection with a plasmid containing the rePON1 gene, increased SR-BI
      expression in MPM-PON1(0), whereas rePON1/H115Gln mutant, or the H115Q/H134Q
      double mutant, which lack catalytic activity, did not stimulate SR-BI expression.
      Lysophosphatidyl choline (LPC) resulting from PON1 action on macrophage PC,
      upregulated SR-BI expression in MPM-PON1(0) via activation of ERK1/2 and PI3K.
      Functionally, HDL bound to MPM-PON1(0) significantly less than to MPM-Control,
      and failed to inhibit tunicamycin-induced apoptosis, but had no significant
      effect on HDL-mediated cholesterol efflux from macrophages. CONCLUSIONS: PON1
      deficiency in mice is associated with decreased macrophage SR-BI expression,
      decreased cellular HDL binding, and consequently the loss of HDL-mediated
      cytoprotection against apoptosis, which may contribute to the accelerated
      atherosclerosis observed in PON1(0) mice. These findings add new insights into
      the function of SR-BI in macrophages, and define the potential role of PON1 in
      regulating SR-BI-mediated HDL protection against macrophages apoptosis.

PMID- 20149375
TI  - The renal artery ostium flow diverter: structure and potential role in
      atherosclerosis.
AB  - Initiation of renal atherosclerosis occurs primarily at the caudal region of the
      renal artery ostium. To date, no mechanism for initiation of atherosclerosis at
      this site has been substantiated. Herein, we identify a renal artery flow
      diverter on the caudal wall of the renal artery ostium that directs flow into the
      renal artery and selectively retains LDL, an initial step in atherosclerosis.
      High-resolution ultrasound revealed the generation of flow eddies by the caudal
      diverter in vivo, consistent with a role in directing aortic flow to the renal
      artery. Two-photon excitation en face microscopy of the diverter revealed a
      substantial reduction in the elastic lamina exposing potential retention sites
      for LDL. Fluorescent LDL was selectively retained by the renal artery diverter,
      consistent with its molecular structure. We propose that the rigid macromolecular
      structure of the renal artery ostium diverter is required for its vascular
      function and contributes to the initiation of renal atherosclerosis by the
      retention of LDL.

PMID- 20149376
TI  - The direct inverse method: a novel approach to estimate adsorption isotherm
      parameters.
AB  - A novel method to estimate adsorption isotherm parameters is presented and its
      applicability is studied through synthetic as well as experimental data. This
      approach assumes a linear dependency of the UV absorption intensity on the solute
      concentration in the fluid phase, at least in certain ranges of the UV spectra.
      It was demonstrated that by fitting the absorption profiles, i.e. the new direct
      inverse method, and by fitting the concentration profiles, i.e. the classical
      inverse method, very similar adsorption isotherm parameters can be obtained. The
      findings presented in this work have as important implication the elimination of
      the requirement of converting a measured absorption intensity into a
      concentration value, i.e. the elimination of the calibration of the UV signal.

PMID- 20149377
TI  - Validation and uncertainty analysis of a multiresidue method for 42 pesticides in
      made tea, tea infusion and spent leaves using ethyl acetate extraction and liquid
      chromatography-tandem mass spectrometry.
AB  - A rapid, specific and sensitive multiresidue method to determine 42 pesticides in
      made tea, tea infusion and spent leaves has been developed and validated for the
      routine analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      The method was reproducible (Horwitz ratio (HorRat) <0.5 at 50 ng/g) and
      validated by the analysis of sample spiked at 50 and 100 ng/g in made tea, tea
      infusion and spent leaves. The samples were extracted with ethyl
      acetate+cyclohexane (9:1; v/v), and the extracts were cleaned up by dispersive
      solid phase extraction with primary secondary amine sorbent+graphitized carbon
      black+Florisil. The recoveries of all the pesticides were between 70% and 120%
      with a relative standard deviation of less than 15% and correlation coefficient
      for each pesticide was R(2) > or =0.99. The matrix effect on signal of respective
      compounds was measured by comparing matrix-matched calibration standards with
      those in solvent-only. The limits of quantitation (LOQ) met the requirements of
      the maximum residue limits (MRLs) for pesticides in tea as recommended by the
      European Union.

PMID- 20149378
TI  - Analysis of hexachlorocyclohexanes in aquatic samples by one-step microwave
      assisted headspace controlled-temperature liquid-phase microextraction and gas
      chromatography with electron capture detection.
AB  - A microwave-assisted headspace controlled-temperature liquid-phase
      microextraction (HS-CT-LPME) technique was applied for the one-step sample
      extraction of hexachlorocyclohexanes (HCHs) from aqueous samples with complicate
      matrices, followed by gas chromatographic (GC) analysis with electron capture
      detector (ECD). Microwave heating was applied to accelerate the evaporation of
      HCHs into the headspace and an external-cooling system was used to control the
      temperature in the sampling zone for HS-LPME. Parameters affecting extraction
      efficiency, such as LPME solvent, sampling position and temperature, microwave
      power and irradiation time (the same as sampling time), sample pH, and salt
      addition were thoroughly investigated. From experimental results, the following
      conditions were selected for the extraction of HCHs from 10-mL water sample (pH
      2.0) by using 1-octanol as the LPME solvent, with sampling done at 38 degrees C
      for 6 min under 167 W of microwave irradiation. The detections were linear in the
      concentration of 0.1-10 microg/L for alpha-HCH and gamma-HCH, and 1-100 microg/L
      for beta-HCH and delta-HCH. Detection limits were 0.05, 0.4, 0.03 and 0.1
      microg/L for alpha-, beta-, gamma- and delta-HCH, respectively. Environmental
      water samples were analyzed with recovery between 86.4% and 102.4% for farm-field
      water, and between 92.2% and 98.6% for river water. The proposed method proved to
      serve as a simple, rapid, sensitive, inexpensive, and eco-friendly procedure for
      the determination of HCHs in aqueous samples.

PMID- 20149379
TI  - Development and validation of a hydrophilic interaction liquid chromatographic
      method for determination of aromatic amines in environmental water.
AB  - A simple, precise, and accurate hydrophilic interaction liquid chromatographic
      (HILIC) method has been developed for the determination of five aromatic amines
      in environmental water samples. Chromatography was carried out on a bare silica
      column, using a mixture of acetonitrile and a buffer of NaH(2)PO(4)-H(3)PO(4) (pH
      1.5, containing 10mM NaH(2)PO(4)) (85:15, v/v) as a mobile phase at a flow rate
      of 1 mL min(-1). Aromatic amines were detected by UV absorbance at 254 nm. The
      linear range of amines was good (r(2)>0.998) and limit of detection (LOD) within
      0.02-0.2 mg L(-1) (S/N=3). The retention mechanism for the analytes under the
      optimum conditions was determined to be a combination of adsorption, partition
      and ionic interactions. The proposed method was applied to the environmental
      water samples. Aromatic amines were isolated from aqueous samples using solid
      phase extraction (SPE) with Oasis HLB cartridges. Recoveries of greater than 75%
      with precision (RSD) less than 12% were obtained at amine concentrations of 5-50
      microg L(-1) from 100mL river water and influents from a wastewater treatment
      plant (WWTP). The present HILIC technique proved to be a viable method for the
      analysis of aromatic amines in the environmental water samples.

PMID- 20149380
TI  - Determination of drugs of abuse in water by solid-phase extraction,
      derivatisation and gas chromatography-ion trap-tandem mass spectrometry.
AB  - An alternative method for the sensitive determination of several drugs of abuse
      and some of their metabolites in surface and sewage water samples is proposed.
      Analytes are concentrated using a solid-phase extraction (SPE) sorbent, converted
      into the corresponding trimethylsilyl derivatives and selectively determined by
      gas chromatography (GC) with tandem mass spectrometry (MS/MS) detection.
      Parameters affecting the performance of extraction, derivatisation and
      determination steps are systematically investigated. Moreover, the stability of
      target analytes in sewage water samples is discussed. Under final working
      conditions, water samples were adjusted at pH 8.5 and concentrated using a 200mg
      OASIS HLB SPE cartridge. Analytes were sequentially eluted with ethyl acetate
      followed by acetone and silylated using N-methyl-N
      (trimethylsilyl)trifluoroacetamide (MSTFA). The reaction was completed in 60 min
      at 80 degrees C and the mixture injected directly in the GC-MS/MS system without
      further purification. In most cases, analytes presented a poor stability in
      sewage water samples; however, once they are submitted to the SPE process,
      cartridges can be stored at -20 degrees C for at least 3 months without
      significant degradation and/or inter-conversion reactions of illicit drugs. The
      proposed method provided recoveries over 74% and LODs between 0.8 and 15 ng/L for
      river and treated wastewater samples. In the case of raw wastewater slightly
      worse recoveries, between 63 and 137%, and similar LODs were attained. Analysis
      of a limited number of waste and surface water samples confirmed the presence of
      several illicit drugs in the aquatic environment, with the highest levels and
      frequency corresponding to benzoylecgonine, the main metabolite of cocaine.

PMID- 20149381
TI  - Thermal desorption/gas chromatography/mass spectrometry approach for
      characterization of the volatile fraction from amber specimens: a possibility of
      tracking geological origins.
AB  - Research on the chemical composition of fossil resins has evolved during the last
      decades as a multidisciplinary field and is strongly oriented toward the
      correlation with their geological and botanical origin. Various extraction
      procedures and chromatographic techniques have been used together for identifying
      the volatile compounds contained in the fossil resin matrix. Hyphenation between
      thermal desorption (TD), gas chromatography (GC) and mass spectrometry detection
      (MS) has been chosen to investigate the volatile compounds fraction from ambers
      with a focus on Romanite (Romanian amber) and Baltic amber species. A data
      analysis procedure was developed for the main purpose of fingerprinting ambers
      based on the MS identity of the peaks generated by the volatile fraction,
      together with their relative percentual area within the chromatogram.
      Chromatographic data analysis was based entirely on Automated Mass Spectral
      Deconvolution &Identification System (AMDIS) software to produce deconvoluted
      mass spectra which were used to build-up a mixed mass spectra and relative
      retention scale library. Multivariate data analysis was further applied on AMDIS
      results with successful discrimination between Romanite and Baltic ambers. A
      special trial was conducted to generate pyrolysis "like" macromolecular structure
      breakdown to volatile compounds by gamma irradiation with a high absorbed dose of
      500 kGy. Contrary to our expectations the volatile fraction fingerprints were not
      modified after irradiation experiments. A complementary non-destructive new
      approach by ESR spectroscopy was also proposed for discriminating between
      Romanite and Baltic ambers.

PMID- 20149382
TI  - Beta-diketones: peak shape challenges and the use of mixed-mode high-performance
      liquid chromatography methodology to obtain fast, high resolution chromatography.
AB  - Historically, indirect methods have been used for the HPLC analysis of beta
      diketone compounds because of the very poor peak shapes and resolution obtained
      on conventional HPLC stationary phases. In this paper we demonstrate that it is
      possible to obtain good peak shapes for underivatised beta-diketone compounds, in
      a simulated reaction mixture, using only conventional mobile phases with mixed
      mode stationary phase HPLC columns. Optimum conditions were obtained using the
      mixed-mode reversed-phase strong anion exchange column Primesep B, supplied by
      SIELC Technologies, with a 0.1% aq. TFA/MeOH gradient method and a column
      temperature of 55 degrees C.

PMID- 20149383
TI  - X-ray absorption spectroscopy study of Cu2+ geochemical partitioning in a
      vineyard soil.
AB  - Associations with soil components are of great importance for bioavailability,
      toxicity, and mobility of trace metals in soils and waters. The copper(II)
      geochemical partitioning during the aging process within a soil sample was
      studied through column experiments combined with extended X-ray absorption fine
      structure (EXAFS) spectroscopy to characterize the copper(II) molecular
      environment.

PMID- 20149384
TI  - A novel multinozzle electrospinning process for preparing superhydrophobic PS
      films with controllable bead-on-string/microfiber morphology.
AB  - Superhydrophobic polystyrene (PS) surfaces with mechanical integrity were
      manufactured by electrospinning in this work. We first report a novel strategy
      here to combine bead-on-string fibers from 4% PS solution and micro-sized fibers
      from 20% PS solution homogeneously in one electrospinning step by multinozzle
      electrospinning. The superhydrophobicity of electrospun sheet can be achieved by
      the presence of bead-on-string fibers, while micro-sized PS fibers are
      responsible for the improvement of mechanical property of electrospun mat due to
      their elastic and flexible behavior. The distinctive design of our multinozzle
      electrospinning setup places two nozzles in separate electrical fields which
      guarantee that fibers with different structures are mixed homogeneously. We
      investigate the relationship between the mass ratio of fibers from two types of
      solutions and the CA of electrospun mat, the effect of mass ratio to the
      mechanical property of electrospun mat can also be observed. The result shows
      that CA value of PS surface merely comprised of bead-on-string fibers could reach
      up to 154.65 degrees . As the content of microfibers increased, the value of CA
      decreased, ranging from 153.66 degrees  to 145.94 degrees , but the tensile
      strength of composite mat was enhanced from 0.50 MPa to 1.22 MPa correspondingly
      which is beneficial to put the mats into practice.

PMID- 20149385
TI  - Alteration of magnetic and optical properties of ultrafine dilute magnetic
      semiconductor ZnO:Co2+ nanoparticles.
AB  - Single-phase ZnO:Co(2+) nanoparticles of mean size 2-8 nm were synthesized by a
      simple co-precipitation technique. X-ray diffraction analysis reveals that the Co
      doped ZnO nanoparticles crystallize in wurtzite structure without any impurity
      phase. The wurtzite structure (lattice constants) of ZnO nanoparticles decrease
      slightly with increasing Co doping concentration. Optical absorption spectra show
      an increase in the band gap with increasing Co content and also give an evidence
      of the presence of Co(2+) ions at tetrahedral sites of ZnO and substituted for
      the Zn site with no evidence of metallic Co. Initially these nanoparticles showed
      strong ferromagnetic behavior at room temperature, however at higher doping
      percentage of Co(2+), the ferromagnetic behavior was suppressed, and
      antiferromagnetic nature was enhanced. The enhanced antiferromagnetic interaction
      between neighboring Co-Co ions suppressed the ferromagnetism at higher doping
      concentrations of Co(2+). Photoluminescence intensity owing to the vacancies
      varies with the Co concentration because of the increment of oxygen vacancies.

PMID- 20149386
TI  - Smectite flocculation structure modified by Al13 macro-molecules--as revealed by
      the transmission X-ray microscopy (TXM).
AB  - The aggregate structure which occurs in aqueous smectitic suspensions is
      responsible for poor water clarification, difficulties in sludge dewatering and
      the unusual rheological behaviour of smectite rich soils. These macroscopic
      properties are dictated by the 3D structural arrangement of smectite finest
      fraction within flocculated aggregates. Here, we report results from a relatively
      new technique, transmission X-ray microscopy (TXM), which makes it possible to
      investigate the internal structure and 3D tomographic reconstruction of the
      smectite clay aggregates modified by Al(13) Keggin macro-molecule
      [Al(13)(O)(4)(OH)(24)(H(2)O)(12)](7+). Three different treatment methods were
      shown resulted in three different micro-structural environments of the resulting
      flocculation. In case of smectite sample prepared in Methods 1 and 3 particles
      fall into the primary minimum where Van der Waals forces act between FF oriented
      smectite flakes and aggregates become approach irreversible flocculation. In case
      of sample prepared using Method 2, particles contacting by edges (EE) and edge to
      face (EF) orientation fell into secondary minimum and weak flocculation resulted
      in severe gelation and formation of the micelle-like texture in fringe
      superstructure, which was first time observed in smectite based gel.

PMID- 20149387
TI  - Interlayer structure of iodide intercalated layered double hydroxides (LDHs).
AB  - The iodide-containing layered double hydroxides (LDHs) of Mg and Zn with Al
      crystallize by the inclusion of extensive positional disorder of I(-) ions in the
      interlayer region. I(-) ion given its poor charge to size ratio can neither
      screen effectively the positive charge nor participate in H-bonding with the
      metal hydroxide layers. Thereby the I(-) ions are not stabilized in sites close
      to the seat of positive charge of the metal hydroxide layers (6c), nor in sites
      that facilitate H-bonding (3b or 18h). On the other hand, OH(-) from water can do
      both and effectively displaces I(-) from the interlayer.

PMID- 20149388
TI  - Long-term behavioral consequences of infant feeding: the limits of observational
      studies.

PMID- 20149390
TI  - Herpes simplex virus testing and hospital length of stay in neonates and young
      infants.
AB  - OBJECTIVE: To examine whether ordering testing of cerebrospinal fluid (CSF) for
      herpes simplex virus (HSV) by polymerase chain reaction (PCR) in neonates and
      young infants is associated with increased hospital length of stay (LOS) or
      increased hospital charges. STUDY DESIGN: This retrospective cohort study
      enrolled infants age <or=56 days who underwent lumbar puncture in the emergency
      department in 2005-2006. The primary "exposure" was CSF HSV PCR, and the primary
      outcomes were LOS and hospital charges. RESULTS: CSF HSV PCR was performed in 282
      of 889 eligible infants (31.7%). The median test turnaround time was 22 hours.
      The median LOS was 2 days, and median hospital charge was $10 166. In
      multivariate analysis, CSF HSV PCR testing was associated with a LOS increase of
      28% for infants age <or=28 days and 39% for infants age 29-56 days. LOS increased
      by 22% for every 12-hour increase in test turnaround time. CSF HSV PCR testing
      was associated with a 41% increase in hospital charges. CONCLUSIONS: In infants
      evaluated by lumbar puncture in the emergency department, CSF HSV PCR testing was
      associated with a significantly longer LOS and higher hospital charges.

PMID- 20149391
TI  - Chronic pain and major depressive disorder in the general population.
AB  - This study aims (1) to assess the prevalence of Chronic Painful Physical
      Condition (CPPC) and major depressive disorder (MDD) in the general population;
      (2) to evaluate their interaction and co-morbidity with sleep and organic
      disorders; and (3) to investigate their daily functioning and socio-professional
      consequences. A random sample of 3243 subjects (18years), representative of
      California inhabitants, was interviewed by telephone. CPPC duration was at least
      6months. Frequency, severity, duration and consequences on daily functioning,
      consultations, sick leave and treatment were investigated. MDD were assessed
      using DSM-IV criteria. The point prevalence of CPPC was 49% (95% confidence
      interval: 47.0-51.0%). Back area pain was the most frequent; 1-month prevalence
      of MDD was at 6.3% (95% CI: 5.5-7.2%); 66.3% of MDD subjects reported at least
      one CPPC. In 57.1% of cases, pain appeared before MDD. Pain severity was
      increased by poor sleep, stress and tiredness in MDD subjects. Being confined to
      bed, taking sick leave and interference of pain with daily functioning were twice
      as frequent among MDD subjects with CPPC than in non-MDD subjects with CPPC;
      obese individuals with CP were 2.6 times as likely to have MDD. Pain is highly
      linked with depressive disorder. It deteriorates physical, occupational and socio
      professional activities. Pain and sleep disturbances are a prime motive of
      consultation rather than depressed mood, underlining the risk of missing a
      depression diagnosis.

PMID- 20149389
TI  - Antithrombotic treatment in neonatal cerebral sinovenous thrombosis: results of
      the International Pediatric Stroke Study.
AB  - OBJECTIVE: To identify predictors of antithrombotic treatment in neonates with
      cerebral sinovenous thrombosis (CSVT) in a large multinational study. STUDY
      DESIGN: Neonates with CSVT from 10 countries were enrolled in the International
      Pediatric Stroke Study from 2003 through 2007. Term neonates with CSVT who
      presented with neurologic symptoms or signs of systemic illness and neuroimaging
      evidence of thrombus or flow interruption within cerebral venous system were
      included. RESULTS: Of 341 neonates enrolled, 84 had isolated CSVT. Neuroimaging
      findings, available in 67/84 neonates, included venous ischemic infarction in 5,
      hemorrhagic infarction or other intracranial hemorrhage in 13, both infarction
      and hemorrhage in 26, and no parenchymal lesions in 23. Treatment data, available
      in 81/84 neonates, included antithrombotic medications in 52% (n = 43),
      comprising heparin (n = 14), low molecular weight heparin (n = 34), warfarin (n =
      1), and aspirin (n = 2). By univariate logistic regression analysis, deep venous
      system thrombosis (P = .05) and location in the United States (P = .001)
      predicted nontreatment. Presence of infarction, hemorrhage, dehydration, systemic
      illness, and age did not predict treatment or nontreatment. In multivariate
      analysis only geographic location remained significant. CONCLUSIONS: In neonatal
      CSVT, regional antithrombotic treatment practices demonstrate considerable
      variability and uncertainty about indications for antithrombotic therapy.
      Additional studies are warranted.

PMID- 20149392
TI  - No association between the FXYD6 gene and schizophrenia in the Chinese Han
      population.
AB  - Choudhury et al. identified FXYD6 as a susceptible gene for schizophrenia in the
      London and Aberdeen populations. We genotyped D11S1998 and 8 SNPs (rs869789,
      rs11216567, rs10790212, rs876797, rs4938445, rs497768, rs11216598, rs11605223) in
      a Chinese sample consisting of 1514 schizophrenia patients and 1514 healthy
      controls. We also compared the expression levels of FXYD6 in lymphocytes in 86
      schizophrenia patients and 94 controls. No association was detected either in
      D11S1998 or the 8 SNPs. No difference was found in expression level between
      patients and controls. Our study suggests that FXYD6 does not play a role in
      schizophrenia in the Chinese Han population.

PMID- 20149393
TI  - Incidence of polycystic ovaries and androgen serum levels in women with
      borderline personality disorder.
AB  - Obesity, increased visceral fat and disturbed glucose metabolism have been found
      in borderline personality disorder (BPD) patients. These conditions are often
      associated with disturbed androgen metabolism. Elevated androgens in women are
      related to polycystic ovaries (PCO) and might have an impact on psychopathology.
      Thus, higher prevalence of PCO and elevated androgen levels are suspected in BPD.
      In the study, we examined 31 BPD patients and 30 healthy controls
      ultrasonographically for PCO and measured their serum levels of androgens and
      interacting hormones. Furthermore, influence on psychopathology of free
      testosterone (FT) serum level was assessed. PCO was significantly more prevalent
      in BPD patients (30.4%) compared to healthy controls (6.9%). Testosterone, FT,
      androstenedione (A), and 17alpha-hydroxyprogesterone (17-OHP) were significantly
      elevated in the BPD group independently of BMI. FT serum level significantly
      correlated with depressive symptoms. In summary, our data suggest a disturbed
      androgen metabolism in BPD patients.

PMID- 20149395
TI  - Light chain deposition in peripheral nerve as a cause of mononeuritis multiplex
      in Waldenstrom's macroglobulinaemia.
AB  - Waldenstrom's macroglobulinaemia is a form of monoclonal IgM gammopathy
      associated with a rare B-cell lympho-plasmacytic lymphoma, characterized by the
      involvement of bone marrow, lymph nodes and spleen. Neurological complications
      involving peripheral nerves are common and different pathogenic mechanisms have
      been reported. We describe a patient with severe multineuropathy associated with
      Waldenstrom's macroglobulinaemia. Nerve biopsy revealed copious light chain
      deposition which subverted the normal architecture of the endoneurium and
      epineurium resulting in massive fascicular hyalinosis and epineural arteries
      disruption, respectively. This report confirms that massive immunoglobulin
      deposition is one of the several mechanisms of nerve damage in IgM-related
      neuropathy. Since their recognition has important therapeutical consequences,
      nerve biopsy is an essential diagnostic tool in patients with an unusual clinical
      presentation of IgM-related neuropathies.

PMID- 20149394
TI  - Clinical features of mitochondrial DNA m.3243A>G mutation in 47 Chinese families.
AB  - m.3243A>G mutation in mitochondrial DNA is the most common pathogenic point
      mutation, causing a variety of phenotypes. To further elucidate its clinical
      characteristics, we recruited 47 Chinese families carrying m.3243A>G mutation and
      analyzed their symptoms, disease history, inheritance, and mitochondria-related
      complications. In the probands, lactic acidosis, myopathy, seizures, short
      stature, weight loss and hirsutism were the most common clinical features. In
      their mothers, lactic acidosis, exercise intolerance, short stature and weight
      loss were the frequent manifestations, and normal phenotype was found in 59.6%
      mothers. m.3243A>G mutation was detected in 47 probands and 42 mothers. In the
      probands, the mutation ratio in blood was threefold higher and the ratio in urine
      was twofold higher than those of their mothers. m.3243A>G mutation ratio in
      mothers' urine and in their probands' blood were weakly correlated. In
      conclusion, (a) stroke-like episode induced by m.3243A>G mutation may be the
      symptom predominantly found in older patients; (b) m.3243A>G mutation ratio
      correlates with the severity of the disease; (c) m.3243A>G mutation ratio in
      mothers' urine may correlate to the ratio in blood in their offspring.

PMID- 20149396
TI  - A zone-specific fish-based biotic index as a management tool for the Zeeschelde
      estuary (Belgium).
AB  - Fish-based indices monitor changes in surface waters and are a valuable aid in
      communication by summarising complex information about the environment (Harrison
      and Whitfield, 2004). A zone-specific fish-based multimetric estuarine index of
      biotic integrity (Z-EBI) was developed based on a 13 year time series of fish
      surveys from the Zeeschelde estuary (Belgium). Sites were pre-classified using
      indicators of anthropogenic impact. Metrics showing a monotone response with
      pressure classes were selected for further analysis. Thresholds for the good
      ecological potential (GEP) were defined from references. A modified trisection
      was applied for the other thresholds. The Z-EBI is defined by the average of the
      metric scores calculated over a one year period and translated into an ecological
      quality ratio (EQR). The indices integrate structural and functional qualities of
      the estuarine fish communities. The Z-EBI performances were successfully
      validated for habitat degradation in the various habitat zones.

PMID- 20149397
TI  - [Myocardial abscess].

PMID- 20149398
TI  - [Urticaria pigmentosa/systemic mastocytosis].

PMID- 20149399
TI  - [Chronic obstructive pulmonary disease on inpatients with heart failure. GESAIC
      study results].
AB  - BACKGROUND AND OBJECTIVE: The clinical relevance of Heart failure (HF) and
      chronic obstructive pulmonary disease (COPD) in the same patient is not well
      established. We decided to study the prevalence of COPD in patients admitted due
      to HF, to define their clinical profile and the relationship with adrenergic beta
      blockers (BB) treatment. PATIENTS AND METHOD: Prospective cohort of inpatients
      with HF admitted in 15 Internal Medicine Services from October 2005 to March
      2006. Diagnosis of COPD was established according to clinical criteria or
      spirometry. Data about neurohormonal treatment (before, during the admission, and
      at discharge) were collected. Statistical analyses were performed using Ji square
      test and T Student test. A logistic regression model was designed with data.
      P<0.05 being considered statistically significant. RESULTS: About 391 patients
      were included . CPOD was present in 25.1% of patients. In two thirds of patients,
      the COPD diagnosis was established by clinical criteria. Regarding GOLD, 23.5% of
      patients had moderate or severe COPD severity. Bivariate analysis showed that
      male (<0.05), poor Charlson's Index and overweight (p=0.04 both) had all
      relationship with COPD. The regression model indicated that only left ventricular
      ejection fraction (LVEF) and BB treatment before admission had statistical
      significance (p=0.03 and p<0.001 respectively). At discharge, 27,6% of patients
      received BB. CONCLUSIONS: COPD in HF patients is common and most frequent
      patients are aged men high comorbidity and overweight. BB treatment is
      conditioned by LVEF, without relationship with COPD severity.

PMID- 20149400
TI  - Prison outbreak: pandemic (H1N1) 2009 in an Australian prison.

PMID- 20149401
TI  - The effects of intravenous nitroglycerine and norepinephrine on gastric
      microvascular perfusion in an experimental model of gastric tube reconstruction.
AB  - BACKGROUND: Esophagectomy with gastric tube reconstruction is the surgical
      treatment for cancer of the esophagus. Perfusion of the anastomotic site of the
      tube depends exclusively on microcirculation, making it susceptible to
      hypoperfusion. It is unknown whether vasodilatation is superior to increased
      perfusion pressure to improve gastric tissue perfusion of the anastomosis.
      METHODS: We performed a gastric tube reconstruction in 12 pigs, mean body weight
      32 +/- 2 kg. Besides systemic hemodynamic parameters, gastric microvascular blood
      flow (MBF) was assessed with laser Doppler flowmetry and gastric microvascular
      HbO(2) saturation (microHbSO(2)) and Hb concentration (microHbcon) with
      spectrophotometry. Animals were randomized over 2 groups: with and without
      intravenous nitroglycerin (NTG). In both groups, mean arterial pressure (MAP) was
      increased from 50 to 110 mmHg with infusion of norepinephrine; in the NTG group,
      central venous pressure was maintained below 10 mmHg throughout the experiment
      with NTG. RESULTS: Except for central venous and pulmonary capillary wedge
      pressures, all hemodynamic parameters were similar in both groups. Especially in
      corpus and fundus, MBF decreased following surgery. However, overall MBF was
      significantly higher in the NTG group. Increasing MAP had no effect on fundus
      MBF. Gastric microHbSO(2) and microHbcon were not different between groups and
      did not change at higher MAP levels. CONCLUSION: In our experimental model of
      gastric tube reconstruction, tissue perfusion is severely compromised; this
      effect is aggravated by systemic hypotension independent from cardiac output.
      Impaired venous outflow might contribute to this effect and can be counteracted
      with infusion of nitroglycerine.

PMID- 20149402
TI  - A meta-analysis comparing conservative treatment versus acute appendectomy for
      complicated appendicitis (abscess or phlegmon).
AB  - BACKGROUND: No standardized approach is available for the management of
      complicated appendicitis defined as appendiceal abscess and phlegmon. This study
      used meta-analytic techniques to compare conservative treatment versus acute
      appendectomy. METHODS: Comparative studies were identified by a literature
      search. The end points evaluated were overall complications, need for
      reoperation, duration of hospital stay, and duration of intravenous antibiotics.
      Heterogeneity was assessed and a sensitivity analysis was performed to account
      for bias in patient selection. RESULTS: Seventeen studies (16 nonrandomized
      retrospective and 1 nonrandomized prospective) reported on 1,572 patients: 847
      patients received conservative treatment and 725 had acute appendectomy.
      Conservative treatment was associated with significantly less overall
      complications, wound infections, abdominal/pelvic abscesses, ileus/bowel
      obstructions, and reoperations. No significant difference was found in the
      duration of first hospitalization, the overall duration of hospital stay, and the
      duration of intravenous antibiotics. Overall complications remained significantly
      less in the conservative treatment group during sensitivity analysis of studies
      including only pediatric patients, high-quality studies, more recent studies, and
      studies with a larger group of patients. CONCLUSION: The conservative management
      of complicated appendicitis is associated with a decrease in complication and
      reoperation rate compared with acute appendectomy, and it has a similar duration
      of hospital stay. Because of significant heterogeneity between studies,
      additional studies should be undertaken to confirm these findings.

PMID- 20149403
TI  - Infrapopliteal arterial reconstructions for limb salvage in patients aged > or
      =80 years according to preoperative ambulatory function and residential status.
AB  - BACKGROUND: Although numerous studies have addressed peripheral
      revascularizations for critical limb ischemia (CLI) in patients aged > or =80
      years, few have focused exclusively on infrapopliteal arterial reconstructions.
      This study aimed to analyze early and long-term outcomes in very elderly patients
      who underwent surgical infrapopliteal revascularization for CLI according to
      their pre-operative ambulatory function and residential status. METHODS: Over an
      18-year period, all consecutive patients aged > or =80 years referred to our
      institution for CLI requiring primary infrapopliteal or inframalleolar arterial
      reconstruction were enrolled in the study. All procedures were completed by the
      same surgeon with patients under regional anesthesia. Patency, limb salvage,
      amputation-free survival, and cumulative survival rates were assessed by Kaplan
      Meier analysis. The patient's pre- and postoperative ambulatory function and
      residential status (at home vs in a nursing home) were also analyzed. The mean
      follow-up was 6.2 years (range, 0.1-11.5) and was obtained for 98% of patients.
      RESULTS: In all, 197 patients (134 men; mean +/- SD age, 82.8 +/- 1.7 years) with
      201 critically ischemic limbs were enrolled in the study. No deaths or fatal
      major complications occurred in the peri-operative period (first 30 days); the
      local complication rate was 6%. After 1 and 7 years, the primary patency rates
      were 88% and 68%, the limb salvage rates were 96% and 87%, the amputation-free
      survival rates were 88% and 39%, and the survival rates were 91% and 44%,
      respectively. At last follow-up or death, 80% of the patients were ambulatory and
      20% were not; 80% lived at home and were independent, another 9% lived at home
      with assistance, and 76% of the sample lived at home and were ambulatory.
      CONCLUSION: Infrapopliteal arterial revascularization in the very elderly with
      CLI proved safe, effective, and durable, confirming that age per se and
      concomitant comorbidities do not necessarily affect technical and clinical
      outcomes. Ambulatory function and independent living status are well preserved
      because, despite a relatively short life expectancy, the majority of very elderly
      revascularized CLI patients can be expected to spend their remaining years
      ambulatory and at home. In contrast, patients with poor ambulatory function or
      who required assistance pre-operatively were less likely to improve their status
      after limb revascularization despite a successful technical result.

PMID- 20149404
TI  - Assessment of the removal and inactivation of influenza viruses H5N1 and H1N1 by
      drinking water treatment.
AB  - Since 2003, there has been significant concern about the possibility of an
      outbreak of avian influenza virus subtype H5N1. Moreover, in the last few months,
      a pandemic of a novel swine-origin influenza A virus, namely A(H1N1), has already
      caused hundreds of thousands of human cases of illness and thousands of deaths.
      As those viruses could possibly contaminate water resources through wild birds
      excreta or through sewage, the aim of our work was to find out whether the
      treatment processes in use in the drinking water industry are suitable for
      eradicating them. The effectiveness of physical treatments (coagulation
      flocculation-settling, membrane ultrafiltration and ultraviolet) was assessed on
      H5N1, and that of disinfectants (monochloramine, chlorine dioxide, chlorine, and
      ozone) was established for both the H5N1 and H1N1 viruses. Natural water samples
      were spiked with human H5N1/H1N1 viruses. For the coagulation-settling
      experiments, raw surface water was treated in jar-test pilots with 3 different
      coagulating agents (aluminum sulfate, ferric chloride, aluminum
      polychorosulfate). Membrane performance was quantified using a hollow-fiber
      ultrafiltration system. Ultraviolet irradiation experiments were conducted with a
      collimated beam that made it possible to assess the effectiveness of various UV
      doses (25-60 mJ/cm2). In the case of ozone, 0.5 mg/L and 1 mg/L residual
      concentrations were tested with a contact time of 10 min. Finally, for chlorine,
      chlorine dioxide and monochloramine treatments, several residual oxidant target
      levels were tested (from 0.3 to 3 mg/L) with contact times of 5-120 min. The
      infectivity of the H5N1 and H1N1 viruses in water samples was quantified in cell
      culture using a microtiter endpoint titration. The impact of coagulation-settling
      on the H5N1 subtype was quite low and variable. In contrast, ultrafiltration
      achieved more than a 3-log reduction (and more than a 4-log removal in most
      cases), and UV treatment was readily effective on its inactivation (more than a 5
      log inactivation with a UV dose of 25 mJ/cm2). Of the chemical disinfection
      treatments, ozone, chlorine and chlorine dioxide were all very effective in
      inactivating H5N1 and H1N1, whereas monochloramine treatment required higher
      doses and longer contact times to achieve significant reductions. Our findings
      suggest that the water treatment strategies that are currently used for surface
      water treatment are entirely suitable for removing and/or inactivating influenza
      A viruses. Appropriate preventive actions can be defined for single disinfection
      treatment plants.

PMID- 20149405
TI  - Metabolic turnover and catalase activity of biofilms of Pseudomonas fluorescens
      (ATCC 17552) as related to copper corrosion.
AB  - In this work we report the results of a combined biochemical and electrochemical
      study aimed to analyze both the growth of biofilms of Pseudomonas fluorescens on
      copper samples and its possible role in the instability of the metal/electrolyte
      interface. DNA and RNA were quantified along the time for biofilms grown on
      copper and glass to estimate both the growth of the bacterial population and its
      metabolic state (through the RNA/DNA ratio). The expression and specific activity
      of catalase were also determined to gain insight into their possible role in
      corrosion acceleration. The electrochemical behavior of the biofilm/copper
      interface was monitored by Linear Polarization Resistance (Rp) and
      electrochemical impedance spectroscopy (EIS) along the experiments. Results
      showed a longer lag phase for biofilms developing on copper that included a
      period of high metabolic activity (as measured by the RNA/DNA ratio) without
      biomass growth. Biological activity introduced a new time constant at
      intermediate frequencies in EIS spectra whose capacitive behavior increased with
      the biofilm development. The increment in this biofilm-related signal was
      accompanied by a strong limitation to charge transfer through a diffusion
      controlled process probably due to oxygen exhaustion by cells respiration, while
      the resistance of the interface decreased presumably due to oxide dissolution by
      local acidification under the colonies. In addition, catalase activity was found
      to be high in mature copper-tolerant biofilms, which differentially express a
      catalase isoform not present in biofilms growing on glass.

PMID- 20149406
TI  - Optimized enzymatic preparation of 1-deoxy-d-xylulose 5-phosphate.
AB  - The preparation of 1-deoxy-d-xylulose 5-phosphate, the key intermediate of MEP
      biosynthetic pathway for terpenoids by using recombinant 1-deoxy-d-xylulose 5
      phosphate synthase of Rhodobacter capsulatus was optimized. The simple one-pot
      synthesis coupling with a newly established ion-exchange purification process
      affords the target compound with more than 80% yield and high purity (>95%). The
      procedure can also be employed to synthesize isotope labeled 1-deoxy-d-xylulose 5
      phosphate by using isotope labeled starting materials.

PMID- 20149407
TI  - Solarization and biosolarization enhance fungicide dissipation in the soil.
AB  - Although there is some evidence regarding the effect of solarization and
      biosolarization on pesticide degradation, information is still scarce. The aim of
      this study was to determine the effect of these disinfection techniques on the
      degradation of eight fungicides (azoxystrobin, kresoxin methyl, tebuconazole,
      hexaconazole, triadimenol, cyprodinil, pyrimethanil and fludioxonil) commonly
      used in pepper crops under greenhouse cultivation. Seventy-five 17-L pots filled
      with clay-loam soil were placed in a greenhouse during the summer season and then
      contaminated with the studied fungicides. Treatments consisted of different
      disinfection treatments, including a control without disinfection, solarization
      and biosolarization. For the solarization and biosolarization treatments, low
      density polyethylene film was used as cover. Five pots per treatment were sampled
      periodically up to 90d after the beginning of each treatment and fungicide
      residues were analyzed by GC/MS. The results showed that both solarization and
      biosolarization enhanced fungicide dissipation rates with regard to the control
      treatment, an effect which was attributed to the increased soil temperature. Most
      of the fungicides studied showed similar behavior under solarization and
      biosolarization conditions. However, triadimenol was degraded to a greater extent
      in the biosolarization than in the solarization treatment, while fludioxonil
      behaved in the opposite way. The results confirm that both solarization and
      biosolarization contribute to pesticide dissipation and can therefore be
      considered alongside other soil disinfection techniques, as a bioremediation tool
      for pesticide-polluted soils.

PMID- 20149408
TI  - Levels of perfluorooctane sulfonate and perfluorooctanoic acid in female serum
      samples from Japan in 2008, Korea in 1994-2008 and Vietnam in 2007-2008.
AB  - Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have recently
      received attention owing to their widespread contamination in the environment.
      One of major manufacturers, 3M Company voluntarily phased out PFOS production in
      2002. We measured the PFOS and PFOA concentrations in serum samples from Japan
      (Sendai, Takayama and Osaka), Korea (Busan and Seoul) and Vietnam (Hanoi) to
      evaluate the possible effects of the phase-out on the serum levels. There were
      spatial differences in both the serum PFOS and PFOA concentrations. The serum
      PFOS concentrations (ngmL(-1)) evaluated as the geometric mean (geometric
      standard deviation) in 2007-2008 ranged from 4.86 (1.45) in Sendai, Japan, to
      9.36 (1.42) in Busan, Korea. The serum PFOA concentrations ranged from 0.575
      (2.32) in Hanoi, Vietnam, to 14.2 (1.73) in Osaka, Japan. Historically archived
      samples collected from Korea in 1994-2008 revealed that the serum PFOA
      concentrations increased by 1.24-fold in Busan from 2000 to 2008 and 1.41-fold in
      Seoul from 1994 to 2007. On the other hand, the serum PFOS concentrations did not
      change from 1994 to 2007/2008. The serum PFOS levels in Japan in 2008 were
      significantly decreased compared with previously reported values (22.3-66.7% of
      the values in 2003/2004). However, the serum PFOA levels showed a clear decline
      from 2003 to 2008 in a high-exposed area, Osaka, but not in low-exposed areas in
      Japan. The trends toward decreases were not uniformly observed in Asian
      countries, unlike the case for the United States, suggesting that local factors
      associated with the production and introduction histories in each country
      overwhelm the effects of the phase-out.

PMID- 20149409
TI  - Impact of ultrasonic power density on hot water elution of severely biodegraded
      heavy oil from weathered soils.
AB  - An ultrasound-enhanced elution system using water at a temperature of 70 degrees
      C was employed to remove severely biodegraded heavy oil (SBHO) from weathered
      soil. The effect of varying the ultrasonic power density from 0 to 100 W L(-1) on
      the elution of SBHO and three characteristic biomarkers (C(26-34) 17alpha 25
      norhopanes, C(26-28) triaromatic steroids (TAS), and C(27-29) methyl triaromatic
      steroids (MTAS) was analyzed using GC/MS, scanning electron microscopy (SEM), and
      X-ray diffraction (XRD). The amount of SBHO and biomarkers present in the treated
      soils and eluent had significant negative correlation with increasing ultrasonic
      power density. Elution of the three biomarkers was closely related to the number
      of C atoms in the marker: C(26-34) 17alpha 25-norhopanes with more carbon numbers
      and MTAS homologs with less carbon numbers were more readily eluted at higher
      power densities. The smaller TAS species were more readily eluted at a power
      density of less than 60 W L(-1), while larger TAS species displayed improved
      elution at power densities greater than 60 W L(-1). SEM images of samples treated
      at higher power densities revealed a more compact SBHO accumulation layer at the
      water-soil interface. The results of XRD and energy spectroscopy experiments
      indicated that ultrasound at a power density of 20 W L(-1) was helpful for the
      formation and sedimentation of calcite, although this effect disappeared at
      higher power of greater than 60 W L(-1).

PMID- 20149410
TI  - Polycyclic aromatic hydrocarbon removal from contaminated soils using fatty acid
      methyl esters.
AB  - In this study, solubilization of PAHs from a manufactured gas plant (MGP) soil
      and two artificially spiked soils using fatty acid methyl esters (FAME) was
      investigated. PAH removals from both the MGP and the spiked soils by FAME,
      methanol, soybean oil, hydroxypropyl-beta-cyclodextrin, Triton X-100, and Tween
      80 were compared. The effect of FAME:MGP soil ratios on PAH removals was also
      investigated. Results showed that the FAME mixture synthesized by our lab was
      more efficient than the cyclodextrin and the two surfactants used for PAH removal
      from the spiked soils with individual PAH concentrations of 200 and 400 mg kg(
      1). However, the difference among three PAH removals by the FAME, soybean oil and
      methanol was not quite pronounced. The FAME synthesized and market biodiesel
      exhibited better performance for PAH removals (46% and 35% of total PAH) from the
      weathered contaminated MGP soil when compared with the other agents (0-31%).
      Individual PAH removals from the weathered MGP soil were much lower than those
      from the spiked soils. The percentages of total PAH removals from the MGP soil
      were 59%, 46%, and 51% for the FAME:MGP soil ratios of 1:2, 1:1, and 2:1,
      respectively. These results showed that the FAME could be a more attractive
      alternative to conventional surfactants in ex situ washing of PAH-contaminated
      soils.

PMID- 20149411
TI  - Biodegradation of gas-phase styrene using the fungus Sporothrix variecibatus:
      impact of pollutant load and transient operation.
AB  - Biofiltration of gas-phase styrene was studied using a newly isolated fungus
      Sporothrix variecibatus, in a perlite biofilter, at inlet concentrations and gas
      flow rates ranging from 0.13 to 14 g m(-3) and 0.075 to 0.34 m(3) h(-1),
      respectively, corresponding to empty bed residence times (EBRT) ranging between
      91 and 20s. Styrene loading rates were varied between 50 and 845 g m(-3) h(-1)and
      a maximum elimination capacity of 336 g m(-3) h(-1) was attained with nearly 65%
      styrene removal. On the other hand, the critical inlet loads to achieve more than
      90% removal were 301, 240 and 92 g m(-3) h(-1) for EBRT of 91, 40, and 20s,
      respectively. In order to test the stability and shock bearing capacity of the
      fungal biofilter, short-term tests were conducted by suddenly increasing the gas
      phase styrene concentration, while maintaining the gas-flow rate constant. The
      response, a restoration in the removal performance to previous high values, after
      subjecting the biofilter to shock loads proves the resilient nature of the
      attached Sporothrix sp. and its suitability for biofiltration under non-steady
      state conditions.

PMID- 20149412
TI  - Lithological influences on occurrence of high-fluoride groundwater in Nagar
      Parkar area, Thar Desert, Pakistan.
AB  - Factors regulating the occurrence of high fluoride (F(-)) concentrations in
      groundwater near Nagar Parkar Town, SE corner of Pakistan have been investigated
      considering lithological influences. F(-) ion concentrations in groundwater range
      up to 7.85 with mean value of 3.33 mg L(-1). Plots of major elements and their
      normative mineral composition reflect granitic composition of the rocks in the
      study area. Modal mineralogical analysis show high perthite, plagioclase
      feldspars and quartz, while micas, amphiboles and pyroxenes occur in minor
      quantities. Water-rock interactions, based on dissolved ions of F(-), SiO(2),
      Na(+), K(+), Mg(2+), Li(+) and Sr(2+) suggest that fluoriferous groundwater
      originates from granitic rocks, typically from albite, biotite, hornblende and
      pyroxene and its alteration products such as kaolin and soil. The Log TDS,
      Na/Na+Ca ratio, Mg/Ca+Mg and Cl/Sigma anions are significant to review the impact
      of weathering processes which promote the availability of F(-) ions in the
      groundwater of study area. Principal component analysis (PCA) also renders close
      association among F(-) ions and other elements in the rocks and groundwater.
      Studies on F(-) estimation in the granite rock, china clay, soil and sand samples
      also indicate the presence of high F(-) concentration in these materials and
      average values have been found to be 1939, 710, 254 and 16 mg kg(-1),
      respectively.

PMID- 20149413
TI  - Use of immunohistochemistry for IgG4 in the distinction of autoimmune
      pancreatitis from peritumoral pancreatitis.
AB  - The patients with autoimmune pancreatitis usually present with jaundice and a
      pancreatic head mass, presumed to have pancreatic cancer, and they often undergo
      pancreatic resection. Elevated serum IgG4 levels (>135 mg/dL) help to distinguish
      autoimmune pancreatitis from pancreatic cancer. However, when the biopsy from a
      pancreatic mass shows dense chronic inflammation and fibrosis and the serum IgG4
      level is not available, it presents a diagnostic dilemma whether it represents
      autoimmune pancreatitis or peritumoral pancreatitis. We performed IgG4
      immunohistochemistry on 25 cases of autoimmune pancreatitis-lymphoplasmacytic
      sclerosing pancreatitis, 7 cases of autoimmune pancreatitis with granulocytic
      epithelial lesions, 8 cases of nonspecific pancreatitis, 15 cases of pancreatitis
      associated with pancreatic ductal adenocarcinoma, and 5 biopsies of pancreatic
      adenocarcinoma with variable inflammation. The distribution of IgG4-positive
      cells was noted in each case. Eighty-four percent (21/25) of autoimmune
      pancreatitis-LPSP cases showed diffuse and dense staining for IgG4, with more
      than 50 positive plasma cells per high-power field (range, 50-150 cells/hpf) in
      the highest density area. Most (5/7) cases of autoimmune pancreatitis
      granulocytic epithelial lesions were negative for IgG4. Thirty-nine percent of
      nonspecific pancreatitis and peritumoral pancreatitis cases stained positive for
      IgG4, but the distribution was focal and none of the cases showed more than 50
      IgG4-positive cells/hpf in the highest density area of IgG4 staining. IgG4
      positive cells in peritumoral pancreatitis and nonspecific pancreatitis cases
      were closely associated with malignant glands and areas of acute inflammation in
      some cases. Using a cutoff of 50 IgG4-positive cells/hpf, the sensitivity of IgG4
      staining for classical autoimmune pancreatitis-LPSP versus other types of
      pancreatitis was 84%, the specificity was 100%, and the P value was significant
      (<.0001). Hence, we conclude that diffuse and dense staining (>50 positive
      cells/hpf) for IgG4 is specifically seen in autoimmune pancreatitis-LPSP, and
      IgG4 staining along with the histologic features and serum IgG4 levels may be
      very helpful in diagnosing autoimmune pancreatitis.

PMID- 20149414
TI  - Comment on Urban et al. "Assessment of human health risks posed by consumption of
      fish from the Lower Passaic River (LPR), New Jersey" (2009,
      doi:10.1016/j.scitotenv.2009.03.004).
AB  - Urban et al. (2009) presented a human health risk assessment for the Lower
      Passaic River that very narrowly defines fish consumption, ignores crab
      consumption, and is not consistent with current NJ or EPA risk assessment
      procedures and guidance. The restrictively defined consumption then leads to
      inappropriate conclusions on the risk of eating fish from this highly
      contaminated estuarine river. The paper underestimates angler exposure to
      contaminated fish, does not evaluate exposure to contaminated crab, and
      underestimates the cancer risks and non-cancer health hazards associated with
      these exposure pathways. The New Jersey Department of Environmental Protection
      along with the NJ Department of Health and Senior Services issues fish and crab
      consumption advisories for all state waters; these advisories should be followed
      for the Passaic River and surrounding waters:
      http://www.state.nj.us/dep/dsr/FishSmartEatSmartNJ.org.

PMID- 20149415
TI  - Tissue factor expression in blood cells.
AB  - The popular concept of TF serving predominantly as a hemostatic envelope
      encapsulating the vascular bed, has recently been challenged by the observation
      that blood of healthy individuals may form TF-induced thrombus under conditions
      entailing shear stress and activated platelets, corroborating the notion of blood
      borne TF. Accordingly, small amounts of TF activity is detected in calcium
      ionophore-stimulated monocytes, whereas it is questionable whether neutrophils
      and eosinophils express TF. Still there are contradicting reports on TF synthesis
      and expression in activated platelets, but when using a very sensitive and
      specific assay for TF activity measurements, we fail to detect TF activity
      associated with platelets activated with various agonists. However, activated
      platelets may play a role in decrypting monocyte TF activity in a process
      entailing transfer of TF to activated platelets in a P-selectin-PSGL-1 reaction
      whereby inactive TF (encrypted) becomes active through the availability of
      clusters of phosphatidylserine. Microparticles from plasma of healthy subjects
      possess weak TF-like activity which is not inactivated by anti-TF antibody.
      Endothelial cells are well documented to synthesize TF by several agonists in
      vitro. In contrast, there is little evidence that these cells are capable of
      synthesizing TF in vivo, and a recent report fails to show that TF on the
      endothelium may play any role in thrombin generation in a murine endotoxemia
      model. It may be concluded that monocytes are the only blood cells that
      synthesize and express TF and which may be the only source for TF-induced
      thrombosis when the endothelium is intact.

PMID- 20149416
TI  - Long-term expression of canine FVIIa in hemophilic dogs.
AB  - The traditional treatment for hemophilia has been by protein replacement. This is
      complicated by the development of inhibitory antibodies to the infused factor
      (Factor VIII [FVIII] or Factor IX [FIX]). High-dose infusion of recombinant
      activated Factor VII (rFVIIa) has a long track record of success in such patients
      but its short-half life limits its use in prophylaxis. We have developed an
      alternative strategy by continuous expression of activated FVII from a transgene
      that is introduced into the host by means of gene transfer. For this, we modified
      the FVII cDNA to introduce a cleavage site between the light and heavy chain that
      would generate a FVII molecule secreted in the two-chain, activated form. Using
      viral-mediated delivery and expression from a liver-specific promoter (or as a
      transgenic approach) we demonstrated the long-term hemostatic efficacy of this
      approach in hemophilic mice. Subsequently, we used the canine version of our
      modified FVII and via gene transfer, showed multi-year phenotypic correction in
      hemophilic dogs, clearly evident by the absence of spontaneous bleeds that are
      characteristic in this animal model. No adverse events were observed throughout
      the study. Remarkably, clinical benefit was also observed in one treated dog
      despite the lack of hemostatic effect by in vitro assays. Overall, the results in
      this large animal model of hemophilia indicate the potential of gene-based
      continuous expression of activated FVII as a therapeutic strategy for hemophilia
      or other coagulation defects currently treated by rFVIIa.

PMID- 20149417
TI  - Flow cytometric analysis using SYBR Green I for genome size estimation in coffee.
AB  - Plant genome size has been measured by flow cytometry using propidium iodide as a
      dye for nuclear DNA staining. However, some authors have reported the occurrence
      of genome size estimation errors, especially in plants rich in secondary
      metabolites, such as the coffee tree. In this context, we tested an alternative
      cytometric protocol using the SYBR Green I as a fluorochrome for
      stoichiometrically staining nuclear double-stranded DNA in Coffea canephora (2x)
      and Coffea arabica (4x). The results showed that the respective mean genome size
      measured from nuclei stained with SYBR Green I and propidium iodide was
      statistically identical. However, the G(0)/G(1) peaks of nuclei stained with SYBR
      Green I exhibited lower coefficient variations (1.57-2.85%) compared to those
      stained with propidium iodide (2.75-4.80%). Coefficient variation statistical
      data suggest that SYBR Green I is adequate for stoichiometric nuclei staining
      using this methodology. Our results provide evidence that SYBR Green I can be
      used in flow cytometry measurements of plants, with the advantages of minimizing
      errors in nuclear DNA content quantification, staining relatively quicker, with
      high affinity, and being less mutagenic than propidium iodide.

PMID- 20149418
TI  - Alterations in the spermatic function generated by obesity in rats.
AB  - In order to assess the effect of obesity on epididymal and germinal epithelia in
      control rats and obese rats induced by a high fat diet, we evaluated the
      epididymal and testicular morphologies, lipid peroxidation in the epididymis,
      leptin serum levels, steroid hormones, insulin, cholesterol, triglycerides,
      glycemia and some spermatobioscopic parameters. No significant difference was
      observed in the levels of insulin, glucose, cholesterol and triglycerides between
      the two groups. Nonetheless, in the obese rats, circulating leptin and estradiol
      levels showed a significant increase and there was a decline in the testosterone
      levels. The same group showed an increase in the lipid peroxidation of the
      epididymis and reduced spermatobioscopic parameters. The heads of the epididymis
      showed morphological differences in obese rats. No significant difference was
      observed between the testes of both groups. There is a clear evidence of an
      effect on sperm in obese rats and this seems to occur in the epididymis.

PMID- 20149419
TI  - Signals from pancreatic mesoderm influence the expression of a pancreatic
      phenotype in hepatic stem-like cell line PHeSC-A2 in vitro: a preliminary study.
AB  - The ex vivo generation of pancreatic cells from adult hepatic stem cells for
      subsequent transplantation has been proposed as a novel treatment for Diabetes
      mellitus. The pancreas and liver, closely related developmentally, may retain a
      shared (hepatopancreatic) stem cell whose plasticity could be exploited to
      differentiate into either lineage, dependent on environmental signals. This novel
      study investigated whether signals from pancreatic mesoderm could induce the
      differentiation of adult hepatic stem cell-like cells into pancreatic endocrine
      cells in vitro. A porcine hepatic stem-like cell line, designated PHeSC-A2, was
      co-cultured with quail pancreatic mesoderm in a Growth Factor Reduced Matrigel
      Ham's F12.ITS culture system. Immunocytochemical studies revealed insulin- and
      glucagon-producing cells. Assessment of nuclear morphology indicated that these
      endocrine cells were PHeSC-A2-derived. It is thus proposed that the PHeSC-A2 cell
      line has a higher level of plasticity than previously indicated. These
      preliminary results and assessment of published data have led to the following
      postulations: (a) permissive signaling from pancreatic mesoderm suffices to
      induce hepatic stem cells to assume a pancreatic lineage, (b) the pancreatic
      phenotype assumed by hepatic stem cells is a default state, (c) the
      differentiation capacity embodied by these cells indicates the existence of a
      hepatopancreatic stem cell lineage.

PMID- 20149420
TI  - Anatomical and histological profile of bronchus-associated lymphoid tissue and
      localization of melatonin receptor types (Mel 1a and Mel 1b) in the lung
      associated immune system of a tropical bird, Perdicula asiatica.
AB  - The histological distribution of the lung-associated immune system (LAIS) and the
      expressional pattern of melatonin receptors are still unknown in birds. The aim
      of the present study was to determine the localization of the bronchus-associated
      lymphoid tissue (BALT nodule) in a tropical bird, the Indian jungle bush quail,
      Perdicula asiatica. We also demonstrate the expression of melatonin receptor
      types (Mel(1a) and Mel(1b)) in order to propose an immunomodulatory role of
      melatonin in LAIS. Localization of melatonin receptors in the lung of the Indian
      jungle bush quail, P. asiatica was supported immunohistochemically and by Western
      blot analysis using specific antibodies for those receptors. Immunolocalization
      for Mel(1b) receptor was noted in the bronchial region of the lungs, in finger
      like projections of mucosal foldings, in lymphocytes in the BALT nodule as well
      as in free form. In contrast, immunolocalization for Mel(1a) receptor was noted
      in various areas of the lung instead of in the bronchial region. Western blot
      analysis showed a single band at 37 and 39kDa for Mel(1a) and Mel(1b) receptors,
      respectively, with the latter showing higher expression. The results demonstrate
      a well-developed LAIS and region-specific distribution of melatonin receptors in
      the lung and provide evidence for a possible functional role for melatonin in the
      LAIS of birds.

PMID- 20149421
TI  - Immunohistochemical study of the principal pancreatic islet of the toadfish,
      Halobatrachus didactylus (Pisces: Batrachoididae).
AB  - The endocrine pancreas of the toadfish, Halobatrachus didactylus, consists of one
      large circular principal islet (Brockman body) located in the dorsal side or neck
      region of the gallbladder, along with various accessory islets of variable sizes
      and shapes, embedded in the exocrine tissue located within the digestive organs
      connecting mesenteries. Islet cells showed variable shapes, angular or fusiform,
      with long cytoplasmic processes, granular cytoplasm, and a large eccentric
      nucleus. Cells were found scattered or as aggregates or cords. Four primary
      endocrine cell types immunoreactive for glucagon (alpha cells), insulin (beta
      cells), somatostatin (delta cells), and pancreatic polypeptide (F cells) were
      identified within the toadfish principal islet. The alpha, delta, and F cells
      were located both at the periphery and in the central regions, while beta cells,
      which were the predominant type, were present only in the central core. alpha and
      delta cells were found in moderate frequencies, while F cells were the least
      abundant. Macroscopically, the Brockman body of H. didactylus is visible as a
      milky white nodule separated from the exocrine tissue. Its size, location, and
      ease of extraction suggest that H. didactylus is suitable as experimental subject
      for biochemical, immunological, and physiological studies of the endocrine
      pancreas including in vitro investigations of hormone production, storage, and
      release.

PMID- 20149422
TI  - Role of renospermatic basal reflow and age on semen quality improvement after
      sclerotization of varicocele.
AB  - OBJECTIVES: To determine the relationship between renospermatic basal reflow at
      color Doppler ultrasound (CDU) evaluation and the improvement in seminal quality
      after sclerotization of varicocele, and the role of patients' age. No clear
      predictive factors are available for selecting patients who will show a better
      seminal improvement after varicocele correction. METHODS: Between 2002 and 2008
      we selected 113 patients with left unilateral varicocele, meeting the criteria of
      low sperm density, no endocrinological failures and no varicocele recidivating.
      Varicocele correction was performed using the retrograde sclerotization technique
      or, if not possible, the anterograde one. Patients underwent a physical
      examination, follicle-stimulating hormone assessment, sperm analysis (density,
      motility, and morphologic analysis), scrotal ultrasound, and CDU evaluation.
      Patients were divided into 5 groups using the CDU classification (Sarteschi).
      Three months postoperatively, they were assessed with the same protocol. Mean age
      was 32.2 years. RESULTS: We found improvement in seminal quality among the entire
      population. We found no significance in differences among semen quality
      improvement in patients of different ages. Patients with basal renospermatic
      reflow at preoperative CDU evaluation (groups 3, 4, and 5) showed a better
      improvement in sperm density (+139%) than patients with no basal reflow (groups 1
      and 2; +61%). CONCLUSIONS: The presence of a basal reflow at preoperative CDU is
      a strong predictive factor of a better seminal quality improvement after
      varicocele correction. On the contrary, patient's age showed no significant
      relationship.

PMID- 20149423
TI  - "Importance of delivered cycles and nomogram for intraperitoneal chemotherapy in
      ovarian cancer".

PMID- 20149424
TI  - Selection for position: the role of left ventrolateral prefrontal cortex in
      sequencing language.
AB  - Patients with damage involving left ventrolateral prefrontal cortex (left VLPFC)
      often show syntactic deficits. They also show exaggerated interference effects
      during a variety of non-syntactic tasks, including picture naming and working
      memory. Conceivably, both deficits could arise from inadequate biasing of
      competitive interactions during language production. To test this hypothesis, we
      manipulated "positional" interference during multi-word naming by priming one of
      the nouns in the same or different position. Experimental case studies of four
      left VLPFC patients revealed that two of the patients showed exaggerated
      positional interference, greater number of errors, including omissions during
      multi-word production, increased production difficulty when the order of nouns
      did not match the predominant English pattern, as well as impaired comprehension
      of non-canonical reversible sentences. These results suggest that these two
      patients had an impairment in "selection for position". Different from the other
      two, their lesions included a subregion of frontal cortex (BA 44/6) that has been
      shown in neuroimaging studies to play a role in sequencing.

PMID- 20149425
TI  - Venous thromboembolism during active disease and remission in inflammatory bowel
      disease: a cohort study.
AB  - BACKGROUND: Patients with inflammatory bowel disease who develop deep vein
      thrombosis or pulmonary embolism often have active disease at the time of
      thromboembolism. We therefore aimed to quantify the risk of venous
      thromboembolism prospectively during different activity phases of inflammatory
      bowel disease. METHODS: From the General Practice Research Database, we matched
      patients with prospectively recorded inflammatory bowel disease from November,
      1987, until July, 2001 with up to five controls by age, sex, and general
      practice. A flare was defined as the period 120 days after a new corticosteroid
      prescription. We used Cox regression analysis with time-varying covariates to
      accommodate changes in the state of inflammatory bowel disease, and whether
      patients were at high risk of venous thromboembolism after hospitalisation.
      FINDINGS: 13 756 patients with inflammatory bowel disease and 71 672 matched
      controls were included in the analysis, and of these 139 patients and 165
      controls developed venous thromboembolism. Overall, patients with inflammatory
      bowel disease had a higher risk of venous thromboembolism than did controls
      (hazard ratio 3.4, 95% CI 2.7-4.3; p<0.0001; absolute risk 2.6 per 1000 per
      person-years). At the time of a flare, however, this increase in risk was much
      more prominent (8.4, 5.5-12.8; p<0.0001; 9.0 per 1000 person-years). This
      relative risk at the time of a flare was higher during non-hospitalised periods
      (15.8, 9.8-25.5; p<0.0001; 6.4 per 1000 person-years) than during hospitalised
      periods (3.2, 1.7-6.3; p=0.0006; 37.5 per 1000 person-years). INTERPRETATION:
      Trials of primary prophylaxis of venous thromboembolism are warranted to find out
      whether this important complication can be prevented. FUNDING: National
      Association for Colitis and Crohn's Disease.

PMID- 20149426
TI  - Prophylaxis of venous thromboembolism in IBD.

PMID- 20149427
TI  - Mediating high levels of gene transfer without cytotoxicity via hydrolytic
      cationic ester polymers.
AB  - Cationic polymers are widely studied as gene-delivery vehicles, but are limited
      by low transfection due to inhibited release of DNA, and high cytotoxicity from
      the requisite positive charges. Here, we introduce a hydrolytic cationic ester
      polymer containing both tertiary and quaternary amines, which packages DNA into
      nanoparticles and then releases DNA upon hydrolysis. Cells were transfected with
      these nanoparticles. Luciferase expression from a polymer with the
      tertiary/quaternary ratio of 1:1 was equal to that obtained using branched
      polyethylenimine (PEI), and expression from an acidified polymer with the ratio
      of 3:1 was 20 times higher than branched PEI. These ratios best balance proton
      sponging from tertiary amines and packaging ability from cations. Importantly, no
      hydrolysed polymer exhibited cytotoxicity; the zwitterionic nature of the
      hydrolysed polymer ensured that the quaternary amines in this work do not cause
      cell death. Hydrolysis is critical for effective and safe gene therapy.

PMID- 20149429
TI  - The application of 3D micropatterning of agarose substrate for cell culture and
      in situ comet assays.
AB  - We report the fabrication of a 3D micropatterned agarose substrate that enables
      the culture of single or multiple cells. Patterning was performed on dried
      agarose using deep UV irradiation leading to 6-microm-deep micropatterns of 25-70
      microm in diameter. Cell adhesion was facilitated by the specific grafting of ECM
      (extra cellular matrix) proteins such as fibronectin into the micropatterns. We
      show that the pattern size induced the adhesion of one or more cells, thus
      allowing precise control of the cell number used in the assay, and that cells
      proliferated similarly as in standard culture conditions. Moreover, cell polarity
      appeared well preserved on this substrate, so polarized cells like hepatoma
      HepaRG cells might maintain their differentiation status and act as primary human
      hepatocytes for hepatotoxicity testing. These 3D patterned culture slides have
      been successfully used for in situ comet assays and there is evidence that the
      genotoxic effects of sub-cytotoxic concentrations of drugs could be analyzed in a
      large number of single HeLa cells. Coupled with the parallel-based design of the
      3D micropatterning, which allows automated image analysis, these results strongly
      indicate that this new cell array system is suitable for high-throughput
      cytotoxicity and genotoxicity screening applications.

PMID- 20149428
TI  - Poly(lactide-co-glycolide) nanoparticle assembly for highly efficient delivery of
      potent therapeutic agents from medical devices.
AB  - Controlled delivery of therapeutic agents from medical devices can improve their
      safety and effectiveness in vivo, by ameliorating the surrounding tissue
      responses and thus maintaining the functional integrity of the devices.
      Previously, we presented a new method for providing simultaneous controlled
      delivery from medical devices, by surface assembly of biodegradable polymer
      nanoparticles (NPs) encapsulating fluorescent dyes. Here, we continue our
      investigation with NPs loaded with therapeutic agents, dexamethasone (DEX) or
      plasmid DNA, and evaluated the bioactivity of the released molecules with
      macrophage cells associated with inflammation. Over a period of one week, NPs
      encapsulating DEX released 24.9+/-0.8ng from the probe surface and was successful
      at suppressing macrophage cell growth by 40+/-10%. This percentage of suppression
      corresponded to approximately 100% drug delivery efficiency, in comparison with
      the unencapsulated drug. DNA NP coatings, in contrast, released approximately 1ng
      of plasmid DNA and were effective at transfecting macrophage cells to express the
      luciferase gene at 300+/-200 relative luminescence/mg total protein. This amount
      of luciferase activity corresponded to 100% gene delivery efficiency. Thus, NP
      coatings were capable of providing continuous release of bioactive agents in
      sufficient quantities to induce relevant biological effects in cell culture
      studies. These coatings also remained intact, even after 14 days of incubation
      with phosphate buffered saline. Although the maximum loading for NP coatings is
      inherently lower than the more established matrix coating, our study suggests
      that the NP coatings are a more versatile and efficient approach toward drug
      delivery or gene delivery from a medical device surface and are perhaps best
      suited for continuous release of highly potent therapeutic agents.

PMID- 20149430
TI  - The in vivo performance of polyvinyl alcohol macro-encapsulated islets.
AB  - Islet transplantation is a method for the treatment of type 1 diabetes mellitus
      (DM) and has been widely performed around the world. The long-term
      cryopreservation of islets shows many advantages in the field of islet
      transplantation. Previous studies have described the development of sheet-type
      polyvinyl alcohol (PVA) macro-encapsulated islets (MEI) to treat type 1 DM
      without any immunotherapy. The present study examined their beneficial effects on
      islet cryopreservation. PVA MEI of Wistar rats were divided into three groups of
      1-day, 7-day and 30-day cryopreservation at -80 degrees C. The 30-day group
      showed a lower recovery rate of the islet number and impaired insulin release in
      comparison to the 1-day group, whereas no significant differences of the in vitro
      results were observed between the 1-day and 7-day groups. The MEI transplantation
      recipient mice in the 1-day and 7-day groups reached normoglycemia for a 4-week
      observation period, and the recipients in 30-day group also showed a significant
      decrease followed by a slightly higher non-fasting blood glucose level. These
      results suggest that the PVA MEI are useful for islet long-term cryopreservation,
      and that the use of cryopreserved PVA MEI may, therefore, be a promising modality
      for performing DM therapy.

PMID- 20149431
TI  - Development of a bifunctional immunoliposome system for combined drug delivery
      and imaging in vivo.
AB  - The diverse characteristics of immunoliposomes provide advantages for utilization
      in drug delivery systems. In this study, we fused the antibody affinity motif of
      protein A (ZZ) with Gaussia luciferase (GLase). The fused protein conjugated with
      an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (GLase-ZZ-His
      mAb) was effectively delivered into glioma cells expressing an activated EGFR
      mutant (EGFRvIII) and the bioluminescence was visualized in the cells.
      Immunoliposomes were further constructed with DSPE-PEG-MAL for covalent GLase-ZZ
      His-mAb conjugation. A fluorescence dye (HPTS) encapsulated in immunoliposomes
      conjugated with GLase-ZZ-His-mAb was effectively delivered into EGFRvIII
      expressing glioma cells. In a murine xenograft model of glioma, moreover,
      specific targeting of the immunoliposomes was visualized in the tumor. This new
      bifunctional immunoliposome system has the potential for drug delivery and
      imaging in vivo.

PMID- 20149432
TI  - An anisotropic nanofiber/microsphere composite with controlled release of
      biomolecules for fibrous tissue engineering.
AB  - Aligned nanofibrous scaffolds can recapitulate the structural hierarchy of fiber
      reinforced tissues of the musculoskeletal system. While these electrospun fibrous
      scaffolds provide physical cues that can direct tissue formation when seeded with
      cells, the ability to chemically guide a population of cells, without disrupting
      scaffold mechanical properties, would improve the maturation of such constructs
      and add additional functionality to the system both in vitro and in vivo. In this
      study, we developed a fabrication technique to entrap drug-delivering
      microspheres within nanofibrous scaffolds. We hypothesized that entrapping
      microspheres between fibers would have a less adverse impact on mechanical
      properties than placing microspheres within the fibers themselves, and that the
      composite would exhibit sustained release of multiple model compounds. Our
      results show that microspheres ranging from 10 - 20 microns in diameter could be
      electrospun in a dose-dependent manner to form nanofibrous composites. When
      delivered in a sacrificial PEO fiber population, microspheres remained securely
      entrapped between slow-degrading PCL fibers after removal of the sacrificial
      delivery component. Stiffness and modulus of the composite decreased with
      increasing microsphere density for composites in which microspheres were
      entrapped within each fiber, while stiffness did not change when microspheres
      were entrapped between fibers. The release profiles of the composite structures
      were similar to free microspheres, with an initial burst release followed by a
      sustained release of the model molecules over 4 weeks. Further, multiple model
      molecules were released from a single scaffold composite, demonstrating the
      capacity for multi-factor controlled release ideal for complex growth factor
      delivery from these structures.

PMID- 20149433
TI  - Synthesis, biophysical properties and pharmacokinetics of ultrahigh molecular
      weight tense and relaxed state polymerized bovine hemoglobins.
AB  - Hemoglobin-based oxygen carriers (HBOC) are currently being developed as red
      blood cell (RBC) substitutes for use in transfusion medicine. Despite significant
      commercial development, late stage clinical results of polymerized hemoglobin
      (PolyHb) solutions hamper development. We synthesized two types of PolyHbs with
      ultrahigh molecular weights: tense (T) state PolyHb (M(W)=16.59 MDa and P(50)=41
      mmHg) and relaxed (R) state PolyHb (M(W)=26.33 MDa and P(50)=0.66 mmHg). By
      maintaining Hb in either the T- or R-state during the polymerization reaction, we
      were able to synthesize ultrahigh molecular weight PolyHbs in distinct quaternary
      states with no tetrameric Hb, high viscosity, low colloid osmotic pressure and
      the ability to maintain O(2) dissociation, CO association and NO dioxygenation
      reactions. The PolyHbs elicited some in vitro RBC aggregation that was less than
      6% dextran (500 kDa) but more than 5% human serum albumin. In vitro, T-state
      PolybHb autoxidized faster than R-state PolybHb as expected from previously
      reported studies, conversely, when administered to guinea pigs as a 20% exchange
      transfusion, R-state PolybHb oxidized faster and to a greater extent than T-state
      PolybHb, suggesting a more complex oxidative processes in vivo. Our findings also
      demonstrate that T-state PolybHb exhibited a longer circulating half-life, slower
      clearance and longer systemic exposure time compared to R-state PolybHb.

PMID- 20149434
TI  - The prevention of peritendinous adhesions by a phospholipid polymer hydrogel
      formed in situ by spontaneous intermolecular interactions.
AB  - Preventing peritendinous adhesions after surgical repair of tendon is difficult.
      In order to establish an ideal anti-adhesion material, we prepared a
      spontaneously forming hydrogel by mixing the aqueous solutions of two polymers,
      poly(MPC-co-methacrylic acid) (PMA) and amphiphilic poly(MPC-co-n-butyl
      methacrylate) (PMB), in the presence of Fe(3+). This PMA/PMB/Fe(3+) hydrogel (MPC
      polymer hydrogel) had a honeycomb microstructure with nanometer-scale pores,
      which resist cell invasion but allow the passage of cytokines and growth factors
      for tendon healing. The dissociation rate of the hydrogel could be controlled by
      changing Fe(3+) concentration, and by examining the viscoelasticity of the
      hydrogel, we determined the optimal Fe(3+) concentration to be 0.05 M. We then
      examined the effects of the in situ application of this MPC polymer hydrogel
      containing 0.05 M Fe(3+) by using two animal models: the rat Achilles tendon
      model and the chicken flexor digitorum profundus tendon model. In both models,
      macroscopic and histological observation revealed that peritendinous adhesions
      were significantly decreased by the hydrogel application. Mechanical analyses
      revealed that the hydrogel prevented peritendinous adhesions but did not affect
      the tendon healing. Because of its characteristic microstructure and excellent
      biocompatibility, we believe that the MPC polymer hydrogel will be ideal for
      preventing peritendinous adhesions.

PMID- 20149435
TI  - Enteric-coated capsules filled with freeze-dried chitosan/poly(gamma-glutamic
      acid) nanoparticles for oral insulin delivery.
AB  - A pH-sensitive nanoparticle (NP) system composed of chitosan and poly(gamma
      glutamic acid) was prepared for the oral delivery of insulin. The biodistribution
      study in a rat model showed that some of the orally administered NPs were
      retained in the stomach for a long duration, which might lead to the
      disintegration of NPs and degradation of insulin. To overcome these problems, we
      freeze-dried NPs and filled them in an enteric-coated capsule. The small angle X
      ray scattering (SAXS) profiles indicated that the freeze-drying process did not
      significantly disrupt the internal structure of NPs; additionally, their pH
      sensitivity was preserved and the insulin release was pH-dependent. The results
      obtained in the native PAGE analysis indicated that the released insulin
      molecules were neither fragmented nor aggregated. Upon oral administration, the
      enteric-coated capsule remained intact in the acidic environment of the stomach,
      but dissolved rapidly in the proximal segment of the small intestine.
      Consequently, all the NPs loaded in the capsule were brought into the small
      intestine, thus enhancing the intestinal absorption of insulin and providing a
      prolonged reduction in blood glucose levels. The relative bioavailability of
      insulin was found to be approximately 20%. These results suggest that the
      formulation developed in the study might be employed as a potential approach for
      the oral delivery of insulin.

PMID- 20149436
TI  - Screening platelet-surface interactions using negative surface charge gradients.
AB  - Negative surface charge density gradients were prepared on fused silica slides
      using selective oxidation of a 3-mercaptopropyltrimethoxysilane (MTS) monolayer
      converting surface thiol groups (-SH) into negatively charged sulfonate (-SO(3)(
      )) groups. The sulfonate-to-thiol gradient samples were characterized by water
      contact angle and electron spectroscopy for chemical analysis (ESCA). Gradients
      were pre-adsorbed with proteins from three different solutions: platelet free
      plasma (PFP), fibrinogen, or albumin in phosphate buffered saline (PBS). Washed
      platelets were perfused over gradient samples in a parallel plate flow chamber
      and platelet adhesion was measured across the gradients using differential
      interference contrast (DIC) microscopy. Gradients pre-adsorbed with PFP showed
      adhesion contrast inversely related to the negative surface charge density. The
      magnitude of the adhesion contrast along the gradient was also dependent on PFP
      concentration. Gradients pre-adsorbed with fibrinogen showed an adhesion maximum
      in the center of the gradient region. Albumin coating of the gradients resulted
      in low overall platelet adhesion with increased adhesion in regions of high
      negative charge density. The effect of gradient orientation with respect to the
      flow was also investigated. Gradients pre-adsorbed with 10% PFP showed different
      adhesion contrast when the platelets were perfused in opposite directions. This
      suggests that platelet adhesion is, in addition to responding to the local
      surface properties, also dependent on the upstream conditions.

PMID- 20149438
TI  - In situ endothelialization of intravascular stents coated with an anti-CD34
      antibody functionalized heparin-collagen multilayer.
AB  - The in-stent restenosis (ISR) and the late stent thrombosis (LAST) represent the
      most common failures of stent implantation and are both mediated at the injured
      endothelium. The natural endothelium healing mechanism provides an approach to
      achieve in situ endothelialization of the implant by stimulating the neighboring
      endothelial cells (ECs) migration or capturing the circulating endothelial cells
      (CEC) directly from the blood circulation. An anti-CD34 antibody functionalized
      multilayer of heparin/collagen is developed here via layer-by-layer assemble. The
      ellipsometry and QCM-D results demonstrate that the multilayer coatings with
      slight glutaraldehyde cross-linking are stable in static incubation and flushing
      conditions, respectively. The in vitro hemocompatibility tests and cell culture
      results indicate that both heparin/collagen multilayers with or without the anti
      CD34 antibody functionalization not only preserve good hemocompatibility, but
      also promote cell attachment and growth notably. While the heparin/collagen
      multilayer coatings show no selectivity in promotion of ECs and smooth muscle
      cells (SMCs), the anti-CD34 antibody functionalized heparin/collagen multilayers
      can specifically promote the attachment and growth of the vascular ECs. The
      metabolic activity assessment and the NO secretion measurements further indicate
      that the adherent ECs on the anti-CD34 antibody functionalized heparin/collagen
      multilayer surface have better viability and possess the specific function of the
      natural vascular ECs. In vivo experiments indicate that the anti-CD34 antibody
      can enrich and accelerate the attachment of the vascular cells onto the stent and
      rapid endothelialization is realized. While no significant difference of
      neointimal hyperplasia is observed between the bare metal stents and
      heparin/collagen multilayer modified stents, the neointimal hyperplasia on the
      anti-CD34 antibody functionalized multilayer modified stents is significantly
      inhibited. The success of the anti-CD34 antibody functionalized heparin/collagen
      multilayer coating in rapid endothelialization and anti-restenosis might indicate
      that the immobilization of ECs specific ligand onto a cytocompatible matrix can
      be a good approach for in situ endothelialization and a possible solution to ISR.

PMID- 20149437
TI  - Human umbilical cord stem cell encapsulation in calcium phosphate scaffolds for
      bone engineering.
AB  - Human bone marrow mesenchymal stem cells (hBMSCs) require an invasive procedure
      to harvest, and have lower self-renewal potential with aging. Umbilical cord
      mesenchymal stem cells (hUCMSCs) are a relatively new stem cell source; this
      study reveals a self-setting and load-bearing calcium phosphate construct that
      encapsulates these stem cells. The flexural strength (mean+/-sd; n=5) of the
      hUCMSC-encapsulating calcium phosphate cement (CPC) increased from (3.5+/-1.1)
      MPa without polyglactin fibers, to (11.7+/-2.1) MPa with 20% of polyglactin
      fibers (p<0.05). hUCMSCs attached to the bone mineral-mimicking scaffold in the
      osteogenic media and differentiated down the osteogenic lineage, yielding
      elevated alkaline phosphatase (ALP) and osteocalcin (OC) gene expressions. ALP
      and OC on the CPC-fiber scaffold was 2-fold those on CPC control without fibers.
      hUCMSCs encapsulated inside the scaffolds retained excellent viability and cell
      density. The encapsulated hUCMSCs inside four different constructs successfully
      differentiated down the osteogenic lineage and synthesized bone minerals, as
      confirmed by mineral staining, SEM, and XRD. The percentage of mineral area
      synthesized by the encapsulated hUCMSCs increased from about 3% at day-7, to 12%
      at day-21 (p<0.05). In conclusion, this study demonstrated that hUCMSCs
      encapsulated in the bioengineered scaffolds osteo-differentiated and synthesized
      bone minerals. The self-setting CPC-chitosan-fiber scaffold supported the
      viability and osteogenic differentiation of the encapsulated hUCMSCs, and had
      mechanical strength matching that of cancellous bone.

PMID- 20149439
TI  - Neuronal adhesion and differentiation driven by nanoscale surface free-energy
      gradients.
AB  - Recent results indicate that, in addition to chemical, spatial and mechanical
      cues, substrate physical cues such as gradients in surface energy may also impact
      cell functions, such as neuronal differentiation of PC12 cells. However, it
      remains to be determined what surface effect is the most critical in triggering
      PC12 cell differentiation. Here we show that, beyond continuously probing the
      surface energy landscape of their environment, PC12 cells are highly sensitive to
      nanoscale chemical heterogeneities. Self-assembled monolayers of alkylsiloxanes
      on glass were used as a culture substrate. By changing the structure, ordering
      and chemical nature of the monolayer, the surface energy distribution is altered.
      While both well-ordered CH(3) terminated substrates and bare glass (OH
      terminated) substrates did not favor PC12 cell adhesion, PC12 cells seeded on
      highly disordered CH(3)/OH substrates underwent enhanced adhesion and prompt
      neuritogenesis by 48 h of culture, without nerve growth factor treatment. These
      data illustrate that surface free-energy gradients, generated by nanoscale
      chemical heterogeneities, are critical to biological processes such as nerve
      regeneration on biomaterials.

PMID- 20149440
TI  - Template synthesized poly(epsilon-caprolactone) nanowire surfaces for neural
      tissue engineering.
AB  - Tissue engineering therapies targeted at nerve regeneration in spinal cord
      injuries (SCI) have broad social and economic benefits to the American
      population. Due to the complicated pathophysiology of SCI, there are very few
      options available for functional regeneration of the spinal column.
      Nanotechnology offers interesting avenues to explore tissue engineering in SCI.
      In this study, we have developed a novel solvent free nanotemplating technique
      for fabricating poly(epsilon-caprolactone) (PCL) surfaces with controlled arrays
      of high aspect ratio substrate-bound nanowires for the growth and maintenance of
      differentiated states of neuronal cells. PC12 cells were used to evaluate the
      ability of nanowire surfaces to promote neuronal phenotypic behavior. Cell
      adhesion, proliferation and viability were investigated for up to 4 days of
      culture using fluorescence microscopy, scanning electron microscopy (SEM) and MTT
      activity. Our results indicate significantly higher cell adhesion and subsequent
      proliferation and viability of PC12 cells cultured on nanowire surfaces as
      compared to control surfaces without any nanoarchitecture. Further, the adhered
      cells were maintained in a differentiated state for 7 days and neuronal network
      formation and expression of neuronal markers were investigated using fluorescence
      microscopy, SEM and immunofluorescence. Cells on nanowire surfaces expressed key
      neuronal markers and demonstrated neuronal phenotypic behavior as compared to the
      cells on control surfaces.

PMID- 20149441
TI  - A functionalizable polyester with free hydroxyl groups and tunable physiochemical
      and biological properties.
AB  - Polyesters with free functional groups allow facile modifications with
      biomolecules, which can lead to versatile biomaterials that afford controlled
      interactions with cells and tissues. Efficient synthesis of functionalizable
      polyesters (Functionalizable polymer is defined as a polymer with functional
      groups that readily react with biomolecules and functionalized biomaterial as one
      already modified with biomolecules.) is still a challenge that greatly limits the
      availability and widespread applications of biofunctionalized synthetic polymers.
      Here we report a simple route to prepare a functionalizable polyester,
      poly(sebacoyl diglyceride) (PSeD) bearing free hydroxyl groups. The key synthetic
      step is an epoxide ring-opening polymerization, instead of the traditional
      polycondensation that produces poly(glycerol sebacate) (PGS) (Wang YD, Ameer GA,
      Sheppard BJ, Langer R. A tough biodegradable elastomer. Nat Biotechnol
      2002;20(6):602-6). PSeD has a more defined structure with mostly linear backbone,
      more free hydroxyl groups, higher molecular weight, and lower polydispersity than
      PGS. Crosslinking PSeD with sebacic acid yields a polymer five times tougher and
      more elastic than cured PGS. PSeD exhibits good cytocompatibility in vitro.
      Furthermore, functionalization by glycine proceeds with high efficiency. This
      versatile synthetic platform can offer a large family of biodegradable,
      functionalized polymers with tunable physiochemical and biological properties
      useful for a wide range of biomedical applications.

PMID- 20149442
TI  - Rat hepatocyte aggregate formation on discrete aligned nanofibers of type-I
      collagen-coated poly(L-lactic acid).
AB  - Primary hepatocytes cultured in three dimensional tissue constructs composed of
      multicellular aggregates maintain normal differentiated cellular function in
      vitro while cultured monolayers do not. Here, we report a technique to induce
      hepatocyte aggregate formation using type-I collagen-coated poly(L-lactic acid)
      (PLLA) discrete aligned nanofibers (disAFs) by providing limited cell-substrate
      adhesion strength and restricting cell migration to uniaxial movement. Kinetics
      of aggregate formation, morphology and biochemical activities of rat hepatocyte
      aggregates were tested over a 15 day culture period. Evidence was provided that
      physical cues from disAFs quickly induced the formation of aggregates. After 3
      days in culture, 88.3% of free hepatocytes on disAFs were incorporated into
      aggregates with an average diameter of 61 +/- 18 microm. Hepatocyte aggregates
      formed on disAFs displayed excellent cell retention, cell activity and stable
      functional expression in terms of albumin secretion, urea synthesis and phase I
      and II (CYP1A and UGT) metabolic enzyme activity compared to monolayer culture of
      hepatocytes on tissue culture plastic (TCP) with type-I collagen as well as on
      meshes of type-I collagen-coated PLLA random nanofibers (meshRFs). These results
      suggest that disAFs may be a suitable method to maintain large-scale hepatic
      cultures with high activity for tissue engineering research and potential
      therapeutic applications, such as bioartificial liver devices.

PMID- 20149443
TI  - PEG-PLA microparticles for encapsulation and delivery of Tat-EGFP to retinal
      cells.
AB  - The efficient and controlled delivery of genes and proteins to retinal cells
      remains a challenge. In this study, we evaluated polyethylene glycol-polylactic
      acid (PEG-PLA) microparticles for encapsulation and delivery of a Transactivator
      of transcription-enhanced green fluorescent protein fusion (Tat-EGFP) to retinal
      cells. Our main objective was to develop a microparticle system that delivers Tat
      EGFP with an initial rapid release (within 24 h) followed by a sustained release.
      We prepared four different formulations of Tat-EGFP encapsulated PEG-PLA
      particles to investigate the effects of protein and polymer concentrations on
      particle morphology and protein release, using scanning electron microscopy (SEM)
      and fluorometry techniques. The optimum formulation was selected based on higher
      protein release, and smaller particle size. The optimum formulation was then
      tested in vitro for cell biocompatibility and protein internalization, and in
      vivo for cellular toxicity following sub-retinal injections into rat eyes. The
      results suggest that PEG-PLA microparticles can deliver proteins in cell culture
      allowing protein internalization in as little as 1 h. In vivo, protein was shown
      to localize within the photoreceptor layer of the retina, and persist for at
      least 9 weeks with no observed toxicity.

PMID- 20149444
TI  - The role of collagen reorganization on mammary epithelial morphogenesis in a 3D
      culture model.
AB  - Collagen-based three-dimensional (3D) in vitro models that recapitulate the
      structural and functional context of normal and malignant tissues provide a
      relevant surrogate to animal models in the study of developmental and
      carcinogenic processes. Human breast epithelial MCF10A cells embedded in a
      collagen gel formed both acinar and tubular structures only when the gel was
      detached (floating) from the cell culture plate's well, and allowed to be
      contracted by the cells. Epithelial phenotype depended upon the time and the
      location within the gel, as ducts formed exclusively on the upper layer of the
      gel while ductal branching occurred earlier in the central area of the gel, and
      gradually progressed toward the periphery. The addition of fibroblasts
      accelerated tubulogenesis. MCF10A cells facilitated the organization of thick
      collagen fibers packed into large bundles at the tip of the ducts and parallel to
      the direction of ductal elongation. In gels that were not detached from the
      well's wall, MCF10A cells organized in monolayer and collagen fibers were aligned
      along the axis of outstretched sprouts stemming from those cellular aggregates.
      Partial gel release induced uniaxial tubulogenesis associated with orderly
      aligned collagen fibers. These results suggest that proper collagen organization
      is necessary for epithelial morphogenesis to occur, and that biomechanical
      interactions between fibers and cells mediated duct formation, elongation and
      branching.

PMID- 20149445
TI  - The use of high-hydrostatic pressure treatment to decellularize blood vessels.
AB  - A decellularization method using high-hydrostatic pressure (HHP) technology
      (>600MPa) is described. The HHP disrupts the cells inside the tissue. The cell
      debris can be eliminated with a simple washing process, producing clean,
      decellularized tissue. In this study, porcine aortic blood vessel was
      decellularized by HHP. The mechanical properties and in vivo performance of the
      decellularized tissue were evaluated. Mechanical properties of the decellularized
      tissue were not altered by the HHP treatment. Reduced inflammation of the
      decellularized tissue was confirmed by xenogenic transplant experimentation. An
      allogenic transplantation study showed that decellularized blood vessel endured
      the arterial blood pressure, and there was no clot formation on the luminal
      surface. In addition, cellular infiltration into the vessel wall was observed 4
      weeks after implantation, suggesting that HHP treatments could be applied widely
      as a high-quality decellularization method.

PMID- 20149446
TI  - A ternary hybrid CdS/Pt-TiO2 nanotube structure for photoelectrocatalytic
      bactericidal effects on Escherichia coli.
AB  - A ternary hybrid CdS/Pt-TiO(2) nanotube (NT) photoelectrode was developed by
      dipping and deposition technique as well as successive ionic layer adsorption and
      reaction (SILAR). Small Pt nanoparticles (NPs) and CdS NPs were effectively
      deposited on both the inside and outside of the TiO(2) NTs. The as-prepared
      hybrid shows enhanced photon absorption and photocurrent generation efficiency.
      Higher bactericidal effect to Escherichia coli was observed on the ternary hybrid
      CdS/Pt-TiO(2) NTs as compared with Pt-TiO(2) NTs or pure TiO(2) NTs.

PMID- 20149447
TI  - The induction of bone formation in rat calvarial defects and subcutaneous tissues
      by recombinant human BMP-2, produced in Escherichia coli.
AB  - We investigated the ability of recombinant human bone morphogenetic protein-2,
      produced from Escherichia coli (ErhBMP-2), to form orthotopic and ectopic bone in
      rat models. BMP-2 was expressed in E. coli and extracted from the inclusion
      bodies. Critical-sized calvarial defects and subcutaneous pouches were created in
      rats, and an absorbable collagen sponge (ACS) was loaded with different doses of
      ErhBMP-2 for implantation. ACS alone and sham surgery controls were also
      included. Implant sites were evaluated by histological and/or histometric
      analyses following a 2- or 8-week healing interval. In the calvarial defect
      model, enhanced bone formation was observed with all doses of ErhBMP-2, while
      only limited amounts of new bone were found in controls. In the ectopic
      subcutaneous implant model, bone formation was clearly observed in all animals
      treated with ErhBMP-2 at 2 weeks. However, at 8 weeks, less new bone formation
      was detected than at 2 weeks. Nevertheless, the remaining new bone showed an
      advanced degree of bone remodeling and more maturity than that observed at 2
      weeks. These results showed that ErhBMP-2 was osteoinductive under controlled in
      vivo conditions. Thus, ErhBMP-2 has definite potential as an alternative to rhBMP
      2 produced in a eukaryotic system for clinical use.

PMID- 20149448
TI  - Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem
      cells.
AB  - Embryonic stem cells (ESCs) are pluripotent and have the ability to differentiate
      into mineralising cells in vitro. The use of pluripotent cells in engineered bone
      substitutes will benefit from the development of bioactive scaffolds which
      encourage cell differentiation and tissue development. Extracellular matrix (ECM)
      may be a suitable candidate for use in such scaffolds since it plays an active
      role in cellular differentiation. Here, we test the hypothesis that tissue
      specific ECM influences the differentiation of murine ESCs. We induced murine
      ESCs to differentiate by embryoid body formation, followed by dissociation and
      culture on ECM prepared by decellularisation of either osteogenic cell (MC3T3-E1)
      or non-osteogenic cell (A549) cultures, or on defined collagen type I matrix. We
      assessed osteogenic differentiation by formation of mineralised tissue and
      osteogenic gene expression, and found it to be significantly greater on MC3T3-E1
      matrices than on any other matrix. The osteogenic effect of MC3T3-E1 matrix was
      reduced by heat treatment and abolished by trypsin, suggesting a bioactive
      proteinaceous component. These results demonstrate that decellularised bone
      specific ECM promotes the osteogenic differentiation of ESCs. Our results are of
      fundamental interest and may help in tailoring scaffolds for tissue engineering
      applications which both incorporate tissue-specific ECM signals and stimulate
      stem-cell differentiation.

PMID- 20149449
TI  - Biohybrid thin films for measuring contractility in engineered cardiovascular
      muscle.
AB  - In vitro cardiovascular disease models need to recapitulate tissue-scale function
      in order to provide in vivo relevance. We have developed a new method for
      measuring the contractility of engineered cardiovascular smooth and striated
      muscle in vitro during electrical and pharmacological stimulation. We present a
      growth theory-based finite elasticity analysis for calculating the contractile
      stresses of a 2D anisotropic muscle tissue cultured on a flexible synthetic
      polymer thin film. Cardiac muscle engineered with neonatal rat ventricular
      myocytes and paced at 0.5 Hz generated stresses of 9.2 +/- 3.5 kPa at peak
      systole, similar to measurements of the contractility of papillary muscle from
      adult rats. Vascular tissue engineered with human umbilical arterial smooth
      muscle cells maintained a basal contractile tone of 13.1 +/- 2.1 kPa and
      generated another 5.1 +/- 0.8 kPa when stimulated with endothelin-1. These data
      suggest that this method may be useful in assessing the efficacy and safety of
      pharmacological agents on cardiovascular tissue.

PMID- 20149450
TI  - Long acting hyaluronate--exendin 4 conjugate for the treatment of type 2
      diabetes.
AB  - Despite clinical exploitation of exendin 4 for the treatment of type 2 diabetes,
      the significantly short half-life requiring twice a day injection has limited the
      wide applications. In this work, a protocol for the synthesis of long acting
      hyaluronate (HA) - exendin 4 conjugate was successfully developed using Michael
      addition chemistry between vinyl sulfone modified HA (HA-VS) and thiolated
      exendin 4. The exendin 4 content could be controlled in the range of 5-30
      molecules per single HA chain with a bioconjugation efficiency higher than 90%.
      The conjugation of exendin 4 with HA resulted in about 20 times improved in vitro
      serum stability maintaining the hypoglycemic and gluco-regulatory bioactivities
      of exendin 4. HA - exendin 4 conjugates showed excellent glucose-lowering
      capabilities in type 2 db/db mice demonstrating protracted hypoglycemic effect up
      to 3 days after a single subcutaneous injection. Furthermore, insulin
      immunohistochemical analysis of islets in db/db mice confirmed the improved
      insulinotropic activity of HA - exendin 4 conjugates. The HA - exendin 4
      conjugates will be investigated further as a twice a week injection dosage form
      for clinical applications.

PMID- 20149451
TI  - The characteristics of sub 10 nm manganese oxide T1 contrast agents of different
      nanostructured morphologies.
AB  - There is continuous interest in developing manganese-based T(1) contrast agents.
      While much effort has been made to synthesize manganese chelates, the development
      of manganese-based nanoparticle, particularly manganese oxides, as MRI contrast
      agents is burgeoning. In this report, sub-10-nm nanospheres, nanoplates, and
      nanocubes of Mn(3)O(4) were synthesized and exhibited paramagnetic behavior at
      room temperature on the basis of superconducting quantum interference devices
      (SQUID) measurements. The surface Mn(3+) passivated nanoplates examined by x-ray
      photoelectron spectroscopy (XPS) had the largest r(1) relaxivity of the reported
      manganese oxide nanoparticles. The MR labeling assays of Mn(3)O(4) nanoplate
      treated A549 lung cancer cells showed that MR signals increased to 139% in T(1)
      weighted images compared with untreated cells when the Mn ion concentration went
      down to 1.3 x 10(-2) mM. A dark field illumination microscope was employed to
      monitor Mn(3)O(4) nanoplates internalized into cells as a function of time.

PMID- 20149452
TI  - Orphan receptor kinase ROR2 is expressed in the mouse uterus.
AB  - OBJECTIVE: Wingless-type mouse mammary tumor virus integration site family,
      member 5A (WNT5A), is expressed in mouse decidua and is thought to play an
      important role in decidualization. We examined expression of the receptor for
      WNT5A, receptor tyrosine kinase-like orphan receptor 2 (ROR2), in the uteri of
      cycling and pregnant mice. STUDY DESIGN: Reverse transcription (RT)-PCR and
      immunohistochemistry were performed. RESULTS: RT-PCR revealed that transcripts
      for Ror2, Wnt3a, Wnt5a and inhibitor of WNT signaling, Dickkopf homolog 1 (Dkk1),
      were present in the pregnant uterus. Immunohistochemistry revealed that in the
      virgin uterus, ROR2 is expressed in stromal cells and on the basal side of
      uterine gland and endometrial epithelial cells. During pregnancy, both the
      luminal and basal side of uterine gland epithelial cells expressed ROR2, stromal
      cell expression of ROR2 became more frequent and ROR2 expressing uterine Natural
      Killer (NK) cells and cells lining the maternal vascular space emerged.
      Immunofluorescence imaging and flow cytometry revealed that although uterine NK
      cells expressed ROR2, NK cells of the spleen were ROR2 negative. CONCLUSION: The
      expression of ROR2 by endometrial epithelial cells may suggest WNT signaling has
      roles in uterine epithelial cell polarity or implantation. Expression of ROR2 by
      uterine NK cells may suggest WNT signaling regulates uterine NK cell functions
      such angiogenesis and regulation of trophoblast migration. In summary, our
      results show that ROR2 expression by maternal uterine cells is influenced by
      pregnancy.

PMID- 20149453
TI  - Review: The placenta is a programming agent for cardiovascular disease.
AB  - Cardiovascular disease remains the number one killer in western nations in spite
      of declines in death rates following improvements in clinical care. It has been
      20 years since David Barker and colleagues showed that slow rates of prenatal
      growth predict mortality from ischemic heart disease. Thus, fetal undergrowth and
      its associated cardiovascular diseases must be due, in part, to placental
      inadequacies. This conclusion is supported by a number of studies linking
      placental characteristics with various adult diseases. A "U" shaped relationship
      between placental-to-fetal weight ratio and heart disease provides powerful
      evidence that placental growth-regulating processes initiate vulnerabilities for
      later heart disease in offspring. Recent evidence from Finland indicates that
      placental morphological characteristics predict risks for coronary artery
      disease, heart failure, hypertension and several cancers. The level of risk
      imparted by placental shape is sex dependent. Further, maternal diet and body
      composition strongly influence placental growth, levels of inflammation, nutrient
      transport capacity and oxidative stress, with subsequent effects on offspring
      health. Several animal models have demonstrated the placental roots of
      vulnerability for heart disease. These include findings that abnormal endothelial
      development in the placenta is associated with undergrown myocardial walls in the
      embryo, and that placental insufficiency leads to depressed maturation and
      proliferation of working cardiomyocytes in the fetal heart. Together these models
      suggest that the ultimate fitness of the heart is determined by hemodynamic,
      growth factor, and oxygen/nutrient cues before birth, all of which are
      influenced, if not regulated by the placenta.

PMID- 20149454
TI  - SOCIC: the store-operated calcium influx complex.
AB  - Depletion of intracellular calcium stores via activation of G-protein-coupled
      receptors associated to the inositol trisphosphate cascade, or by the blockade of
      the endoplasmic reticulum calcium APTase (SERCA) results in the activation of
      calcium influx via the so-called store-operated channels (SOCs). The recent
      identification of STIM1 as the putative sensing molecule responsible for
      communicating the depleted state of intracellular calcium stores to the plasma
      membrane channel highlights the relevance of protein complexes in calcium
      signaling. Further developments in this area identify Orai as part of the store
      operated channel complex. Upon depletion of intracellular calcium stores, STIM1
      (at the ER) and Orai (at the plasma membrane) aggregate into macromolecular
      complexes. This molecular aggregation appears to be necessary to induce
      activation of calcium influx. Several studies have identified novel members from
      what I would like to define here as the store-operated calcium influx complex
      (SOCIC), such as the TRPC1 channel, SERCA and the microtubule end tracking
      protein, EB1. An orchestrated series of events involving the association and
      dissociation of several protein complexes culminate with the activation of
      calcium influx upon depletion of the ER. There are other likely players in this
      sophisticated signaling mechanism, waiting to be uncovered. The SOCIC assembly
      does not appear to occur in random areas of the plasma membrane, but rather in
      highly specialized areas known as lipid raft domains. These results strongly
      suggest that not only proteins but lipids also may be part or active players in
      the modulation of the store-operated calcium entry (SOCE). In this review we will
      analyze the evidence supporting macromolecular complex assembly as a prerequisite
      for SOC activation. We will highlight the evidence showing novel members from
      SOCIC and speculate about possible yet undiscovered members and players in this
      highly regulated calcium signaling mechanism. Finally we will discuss about the
      role of lipid raft domains in controlling store- and agonist-activated calcium
      influx.

PMID- 20149455
TI  - Abnormal phenotype of bone marrow plasma cells in patients with chronic myeloid
      leukemia undergoing therapy with Imatinib.
AB  - Imatinib induces several effects on the immune system, including
      hypogammaglobulinemia and has been associated with multiple myeloma in some
      patients. We studied the phenotype of plasma cells from patients with chronic
      myeloid leukemia (CML) undergoing therapy with Imatinib mesylate (Glivec). Bone
      marrow samples from 30 CML patients were evaluated and plasma cells were
      identified by multiparametric flow cytometry. In 21 patients an abnormal plasma
      cell phenotype, characterized by the absence of CD19, was registered, with 12
      patients expressing also the CD56 molecule. A significant correlation between
      abnormal plasma cell phenotype and reduced gamma-globulin levels was found.
      Immunofixation was always negative. Therapy with Imatinib for CML seems to induce
      a plasma cell phenotype with the same characteristics as monoclonal gammapathies.
      These findings deserve further studies and suggest to monitor plasma protein
      electrophoresis and gamma-globulin levels in all patients treated with Imatinib.

PMID- 20149456
TI  - Toxicity of ionic liquids on the growth, reproductive ability, and ATPase
      activity of earthworm.
AB  - To evaluate the toxicity of the ionic liquid 1-methyl-3-octylimidazolium bromide
      ([C(8)mim]Br) to Eisenia foetida, effects of [C(8)mim]Br on the growth,
      reproductive ability, and adenosine triphosphatase (ATPase) activity of
      earthworms were determined under laboratory conditions using artificial soil as
      substrate. The results showed that [C(8)mim]Br in high concentrations
      significantly inhibited the growth of the earthworms. These effects were enhanced
      with prolonged exposure to and increasing concentration of [C(8)mim]Br. E.
      foetida's reproductive ability was significantly inhibited after 42d of
      subchronic exposure to [C(8)mim]Br at a concentration >or=5 mg kg(-1) artificial
      soil (dry weight). During acute exposure, a high concentration of [C(8)mim]Br
      >or=40 mg kg(-1) artificial soil (dry weight) inhibited the activities of Na(+)
      K(+)-ATPase and Mg(++)-ATPase after 3 and 7d of exposure. After 42d of subchronic
      exposure, the activity of both ATPases was inhibited in groups exposed to
      >or=5mg[C(8)mim]Brkg(-1) artificial soil (dry weight). These results indicate
      that treatment with the ionic liquid [C(8)mim]Br affects the growth, reproductive
      ability, and ATPase activity of earthworms E. foetida.

PMID- 20149457
TI  - Metallic trace element body burdens and gene expression analysis of biomarker
      candidates in Eisenia fetida, using an "exposure/depuration" experimental scheme
      with field soils.
AB  - Smelting plant activities lead to the accumulation of Metal Trace Elements (MTEs)
      in soils. The presence of high concentrations of MTEs can generate an
      environmental stress likely to affect macroinvertebrates living in close soil
      contact such as the Annelida Oligochaeta. Eisenia fetida, an ecotoxicologically
      important test species, was successively exposed to two field soils: (1) a highly
      contaminated agricultural topsoil collected near the former smelter Metaleurop
      Nord (Noyelles-Godault, France) which contaminated surrounding soils by its
      atmospheric emissions [exposure phase], and then (2) a slightly contaminated
      topsoil from an urban garden located in the conurbation of Lille (Wambrechies)
      [depuration phase]. Two analyses were performed during each phase. Firstly, the
      gene expression levels of four biomarker candidates identified in previous
      studies were analyzed in E. fetida coelomocytes. These candidates are Cd
      metallothionein, phytochelatin synthase, coactosin-like protein and lysenin.
      Secondly, the body burdens of the following elements Cd, Pb, Zn, Cu, Fe, Ca, and
      P were measured. Moreover, both analyses were also performed in Lumbricus
      rubellus, an Annelid species collected from the two tested soil-originating
      sites. Analysis of gene expression and MTE body burdens in both species are
      discussed to: (1) evaluate expression biomarkers; (2) gain insight the
      detoxification processes and the long-term response to a metallic stress and (3)
      compare the responses observed in a test species (E. fetida) with the responses
      of a field species (L. rubellus).

PMID- 20149458
TI  - Biochemical biomarkers in Oreochromis niloticus exposed to mixtures of
      benzo[a]pyrene and diazinon.
AB  - Biochemical biomarkers (the activities of acetylcholinesterase, 7-ethoxyresorufin
      O-deetilase, carboxylesterase, catalase, glutathione peroxidase and glutathione S
      transferase) were evaluated in Nile tilapia (Oreochromis niloticus) that had been
      exposed to benzo[a]pyrene (BaP) and the organophosphate pesticide diazinon (DZ),
      at 0.5mg/L. The animals were pre-exposed to BaP for three days, and DZ was then
      added to both non-exposed and pre-exposed groups, being exposed for 2 and 7
      additional days. The level of BaP was also measured in the bile. BaP caused the
      induction of phase I and II enzymes, and DZ caused carboxylesterase inhibition in
      gills but not in liver. AChE activity was unchanged. No significant modulation
      was observed in antioxidant enzymes. When in combination with BaP, DZ caused a
      significant decrease of EROD and GST induction. Levels of BaP in the bile were
      also increased in fish exposed to BaP combined with DZ, indicating an
      interference of DZ in responses activated by BaP.

PMID- 20149459
TI  - Prolonged effect of BAFF on chicken B cell development revealed by RCAS
      retroviral gene transfer in vivo.
AB  - Chickens provide an important model for developmental biology as well as
      phylogenetic studies of the immune system. In many species cytokines are
      important regulators of immune functions and recently we identified the chicken
      homologue of BAFF (B cell activating factor of the TNF family), shown to be an
      essential survival factor for B cells in mammals. Characterisation of BAFF
      function in the phylogenetically distant chicken requires in vivo studies, but
      despite considerable progress to date no efficient transgene or knockout
      technology for chickens is available. Thus the retroviral vector system RCAS
      (replication-competent ASLV long terminal repeat (LTR) with a Splice acceptor)
      was used to generate chickens stably expressing chBAFF or a soluble chBAFF
      neutralizing decoy receptor. Expression of RCAS based proteins was demonstrated
      in ovo and for the complete observation period of 2 month after hatch. In
      contrast to injections with recombinant proteins the prolonged RCAS based
      cytokine expression allowed assessment of BAFF function not only in newly hatched
      chicks but also in more mature birds. We demonstrate that RCAS based secreted
      products were biologically active, with chBAFF overexpression leading to a
      drastic and continuous increase in B cell numbers and neutralisation of chBAFF by
      expression of a soluble decoy receptor leading to severely reduced B cell numbers
      in transduced birds. This increase in B cell numbers was matched by increased
      immunoglobulin levels. Using RCASBP transduced birds we provide evidence that the
      RCAS system provides a fast and highly efficient gene transfer system for
      analysis of secreted protein function in the chicken and we show that in the
      chicken BAFF is necessary for B cell survival but in contrast to mammals, not
      only mature B cells but also immature B cells in the bursa of Fabricius are
      maintained by BAFF.

PMID- 20149460
TI  - A novel mutation in the signal transducer and activator of transcription 3
      (STAT3) gene, in hyper-IgE syndrome.
AB  - The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by
      a highly elevated serum IgE, recurrent staphylococcal skin abscesses and cyst
      forming pneumonia. Non-immunological abnormalities, including a distinctive
      facial appearance, hyperextensive joints, scoliosis, fracture following minor
      trauma, and the retention of primary teeth are also observed in many patients.
      Recently, it was shown that heterozygous mutations in signal transducer and
      activator of transcription 3 (STAT3), can cause autosomal-dominant HIES. Here we
      identify and characterize a novel mutation in the DNA-binding domain of STAT3 in
      a patient with hyper-IgE syndrome. Sequence analysis revealed a de novo
      heterozygous transition of a G-to-A, causing a substitution of a glycine residue
      for an aspartic acid in the translated sequence (G342D). The patient has normal
      levels of STAT3, which is able to translocate to the nucleus upon IL-6
      stimulation. However, enzyme-linked DNA-protein interaction analysis showed that
      the G342D mutation affects the binding ability of STAT3 to target DNA sequences.
      In addition, as shown by qRT-PCR, the mutation abrogates the STAT3-dependent
      transcription of the retinoid-related orphan receptor gammat (ROR gammat) gene,
      an indispensable transcription factor for the commitment of naive CD4+ T cells to
      the Th17 lineage. These data suggest that the novel G342D mutation affects the
      binding of STAT3 on DNA and the STAT3-dependent expression of ROR gammat mRNA,
      leading to the HIES phenotype.

PMID- 20149461
TI  - Pt(II) and Ag(I) complexes with acesulfame: crystal structure and a study of
      their antitumoral, antimicrobial and antiviral activities.
AB  - Two new complexes of platinum(II) and silver(I) with acesulfame were synthesized.
      Acesulfame is in the anionic form acesulfamate (ace). The structures of both
      complexes were determined by X-ray crystallography. For K(2)[PtCl(2)(ace)(2)] the
      platinum atom is coordinated to two Cl(-) and two N-acesulfamate atoms forming a
      trans-square planar geometry. Each K(+) ion interacts with two oxygen atoms of
      the S(O)(2) group of each acesulfamate. For the polymeric complex [Ag(ace)](n)
      the water molecule bridges between two crystallographic equivalent Ag1 atoms
      which are related each other by a twofold symmetry axis. Two Ag1 atoms, related
      to each other by a symmetry centre, make bond contact with two equivalent oxygen
      atoms. These bonds give rise to infinite chains along the unit cell diagonal in
      the ac plane. The in vitro cytotoxic analyses for the platinum complex using HeLa
      (human cervix cancer) cells show its low activity when compared to the vehicle
      treated cells. The Ag(I) complex submitted to in vitro antimycobacterial tests,
      using the Microplate Alamar Blue (MABA) method, showed a good activity against
      Mycobacterium tuberculosis, responsible for tuberculosis, with a minimal
      inhibitory concentration (MIC) value of 11.6microM. The Ag(I) complex also
      presented a promising activity against Gram negative (Escherichia coli and
      Pseudomonas aeruginosa) and Gram positive (Enterococcus faecalis) microorganisms.
      The complex K(2)[PtCl(2)(ace)(2)] was also evaluated for antiviral properties
      against dengue virus type 2 (New Guinea C strain) in Vero cells and showed a good
      inhibition of dengue virus type 2 (New Guinea C strain) replication at 200microM,
      when compared to vehicle-treated cells.

PMID- 20149462
TI  - Synthesis, characterization and cytotoxic activity of gallium(III) complexes
      anchored by tridentate pyrazole-based ligands.
AB  - Reactions of GaCl(3) with pyrazole-containing ligands of the pyrazole-imine
      phenol (HL(1)-HL(3)) or pyrazole-amine-phenol (HL(4)-HL(6)) types led to the
      synthesis of well-defined [GaL(2)](+) homoleptic complexes (1-6). Complexes 1-6
      were characterized by elemental analysis, ESI-MS (electrospray ionization-mass
      spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X
      ray diffraction analysis. In complexes 1-3, the pyrazole-imine-phenolate ligands
      act as monoanionic chelators that coordinate to the metal in a meridional
      fashion, while 4-6 contain monoanionic and facially coordinated pyrazole-amine
      phenolate ligands. Complexes 1-3 have a greater stability in solution compared to
      4-6, which have shown a more pronounced tendency to release the respective
      ancillary ligands. The cytotoxicity of 1-6 and of the respective ligands (HL(1)
      HL(6)) was evaluated against human prostate cancer cells PC-3 and human breast
      cancer cells MCF-7. The substituents of the phenolate rings strongly influenced
      the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride
      substituents at the phenolate rings have shown the highest cytotoxicity,
      including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3
      and 6 is very similar to the one displayed by the respective anchor ligands,
      respectively HL(1) and HL(6). The cytotoxic activity of 3 and 6 is slightly
      increased by the presence of transferrin, and both complexes provoke cell death
      mainly by induction of apoptotic pathways.

PMID- 20149463
TI  - Effects of environmental and artificial UV-B radiation on freshwater prawn
      Macrobrachium olfersi embryos.
AB  - The recent decrease of the stratospheric ozone has resulted in an increase of
      ultraviolet-B (UV-B) radiation reaching the Earth's surface. In freshwater
      ecosystems with transparent water, UV-B rays easily penetrate and potentially
      cause harmful effects to organisms. In this study, embryos of the prawn
      Macrobrachium olfersi were used to evaluate the impact of UV-B rays in freshwater
      environments. We observed three groups of embryos: the first was to assess
      whether UV-B radiation produced morphological defects and/or biochemical
      impairments in the laboratory. The second was to check whether embryos with the
      same impairments as those observed in the laboratory were found in their
      environment, under natural solar radiation. The third group was the non
      irradiated control. The embryos irradiated with 310 mW cm(-2) UV-B for 30 min
      showed morphological alterations similar to those observed in embryos from the
      environmental control group. The most important effects of the UV-B radiation
      observed in M. olfersi embryos were morphological (1.2% of the total number of
      embryos from the environment and 2.8% of the total number of irradiated embryos),
      pigmentation changes in the eyes (78.0% of the total number of embryos from the
      environment and 98.9% of the total number of irradiated embryos), and disruption
      of the chromatophores (46.9% of the total number of embryos from the environment
      and 95.5% of the total number of irradiated embryos). We also observed an
      increase in egg volume, which was accompanied by a significant increase in water
      content in UV-B irradiated groups when compared with aquaria control embryos. In
      addition, a significant decrease in the mitotic index in eggs exposed to UV-B
      radiation was detected (0.17 for the embryos from the aquaria control, 0.10 for
      the embryos of the environmental control, and 0.04 for the irradiated groups).
      The low levels of NPSH and high levels of TBARS indicated that UV-B rays directly
      compromised the antioxidant function of the embryonic cells, leading to oxidative
      stress. Our combined morphological and biochemical analyses revealed important
      effects induced by UV-B on M. olfersi embryos, and the results suggest that the
      recent changes in global conditions may have injurious effects, at least on the
      embryos of freshwater prawns.

PMID- 20149464
TI  - Effects of monocrotophos on the reproductive axis in the male goldfish (Carassius
      auratus): potential mechanisms underlying vitellogenin induction.
AB  - Monocrotophos (MCP) is a highly toxic organophosphorus pesticide that has been
      banned in many countries. Both vitellogenin mRNA expression and secretion were
      significantly induced in male goldfish by exposure to an MCP-based pesticide,
      suggesting that MCP has significant estrogenic properties. To elucidate the
      mechanisms of action of MCP on vitellogenin induction, we used radioimmunoassay
      to examine the effect of MCP treatment on plasma 17beta-estradiol and
      testosterone levels in male goldfish (Carassius auratus). We also investigated
      the potential impacts of MCP treatment on aromatase expression, on the synthesis
      and secretion of pituitary gonadotropins and on the regulation of hypothalamic
      gonadotropin-releasing hormones by real-time PCR and radioimmunoassay.
      Experiments were carried out during the period of gonadal late recrudescence
      following a 21-day exposure to 0.01, 0.10 and 1.00 mg L(-1) of a pesticide
      containing 40% MCP in a semi-static exposure system. The results indicated that
      males in each MCP treatment group had much higher plasma levels of 17beta
      estradiol, suggesting that the induction of VTG production by MCP was indirectly
      caused by elevated levels of endogenous 17beta-estradiol. MCP-induced plasma
      17beta-estradiol levels via interference with the reproductive axis at multiple
      potential sites in male goldfish: (a) MCP exposure enhanced the mRNA expression
      of gonadal aromatase, the enzyme that converts androgens into estrogens,
      consequently reducing plasma levels of testosterone and increasing plasma
      concentrations of 17beta-estradiol; (b) MCP treatment increased follicle
      stimulating hormone beta subunit mRNA expression and protein secretion and
      decreased luteinizing hormone beta subunit mRNA expression and protein secretion,
      thus interfering with gonadotropin synthesis and secretion at the pituitary level
      and leading to the disruption of reproductive endocrine control and androgen and
      estrogen balance.

PMID- 20149465
TI  - Toxic effects and bioaccumulation of the herbicide isoproturon in Tubifex tubifex
      (Oligocheate, Tubificidae): a study of significance of autotomy and its utility
      as a biomarker.
AB  - Tubifex is the only animal reported to respond with autotomy to contamination.
      This response of contaminated worm is understood as a mode of metal excretion.
      Few data concern the potential of organic compounds to induce tubifex autotomy.
      The objective of this study was to investigate if autotomy can be induced by a
      herbicide isoproturon (IP) and be related to the way of excretion. Isoproturon
      accumulation in worm tissues and its effect on tubifex mortality, autotomy and
      regeneration rates were analysed after 4 and 7 days of exposure to the herbicide
      and also when worms were replaced for 10 days in clean water. IP accumulated in
      the same way in all parts of the worm body but IP metabolite rates were
      significantly higher in the posterior part of the worm. Thus the loss of the
      posterior part allows the worm to eliminate an important amount of pesticide.
      Autotomy has a population importance and is related to the degree of worm
      contamination so it may become an interesting biomarker.

PMID- 20149466
TI  - Bioaccumulation of arsenic from water and sediment by a deposit-feeding
      polychaete (Arenicola marina): a biodynamic modelling approach.
AB  - Arsenic bioaccumulation in the deposit-feeding polychaete Arenicola marina has
      been investigated using biodynamic modelling. Radiotracer techniques were used to
      determine the rates of uptake of As as arsenate from water and sediment and its
      subsequent efflux in the laboratory. Lugworms accumulated As from solution
      linearly at concentrations of 2-20 microg l(-1), with a corresponding uptake rate
      constant of 0.1648+/-0.0135 l g(-1)d(-1). 7.8+/-0.8% (assimilation efficiency) of
      the As ingested bound to sediments was retained after egestion of unassimilated
      metal. Elimination of As followed a two-compartment model, with mean efflux rate
      constants (from the slow pool) very similar for As accumulated from solution and
      ingested sediments (0.0449+/-0.0034 and 0.0478+/-0.0225 d(-1), respectively) and
      a corresponding biological half-time of roughly 15 d. A biodynamic model was
      constructed and validated through the comparison of biodynamic model predictions
      against measured bioaccumulated concentrations in lugworms from five UK
      estuaries. The model accurately predicted bioaccumulated As concentrations in
      lugworms using mean values of relevant physiological parameters (uptake rate,
      efflux rate and growth rate constants), a site-specific ingestion rate
      (calculated according to mean worm size and sediment organic matter content and
      expressed as the rate of ingestion of the mass of fine sediment), a site-specific
      sediment concentration measured after HCl extraction, and a standard dissolved As
      concentration. This combination of parameters showed that sediment ingestion
      contributed 30-60% of the total As accumulated by lugworms at the studied sites,
      depending on the different geochemistry at each site. This study showed that it
      is difficult to predict accurately As bioaccumulation at sites with different
      chemistries, unless that chemistry is taken into account.

PMID- 20149467
TI  - Guidelines for reporting of biocatalytic reactions.
AB  - Enzymes and whole cells are being increasingly applied in research and industry,
      but the adoption of biocatalysis relies strongly on useful scientific literature.
      Unfortunately, too many published papers lack essential information needed to
      reproduce and understand the results. Here, members of the scientific committee
      of the European Federation of Biotechnology Section on Applied Biocatalysis
      (ESAB) provide practical guidelines for reporting experiments. The document
      embraces the recommendations of the STRENDA initiative (Standards for Reporting
      Enzymology Data) in the context of pure enzymology and provides further
      guidelines and explanations on topics of crucial relevance for biocatalysis. In
      particular, guidelines are given on issues such as the selectivity, specificity,
      productivity and stability of biocatalysts, as well as on methodological problems
      related to reactions in multiphase systems. We believe that adoption and use of
      these guidelines could greatly increase the value and impact of published work in
      biocatalysis, and hence promote the further growth of applications.

PMID- 20149469
TI  - Multijoint kinetic chain analysis of knee extension during the soccer instep
      kick.
AB  - Although previous studies have shown that motion-dependent interactions between
      adjacent segments play an important role in producing knee extension during the
      soccer instep kick, detailed knowledge about the mechanisms underlying those
      interactions is lacking. The present study aimed to develop a 3-D dynamical model
      for the multijoint kinetic chain of the instep kick in order to quantify the
      contributions of the causal dynamical factors to the production of maximum
      angular velocity during knee extension. Nine collegiate soccer players
      volunteered to participate in the experiment and performed instep kicking
      movements while 3-D positional data and the ground reaction force were measured.
      A dynamical model was developed in the form of a linked system containing 8
      segments and 18 joint rotations, and the knee extension/flexion motion was
      decomposed into causal factors related to muscular moment, gyroscopic moment,
      centrifugal force, Coriolis force, gravity, proximal endpoint linear
      acceleration, and external force-dependent terms. The rapid knee extension during
      instep kicking was found to result almost entirely from kicking leg centrifugal
      force, trunk rotation muscular moment, kicking leg Coriolis force, and trunk
      rotation gyroscopic-dependent components. Based on the finding that rapid knee
      extension during instep kicking stems from multiple dynamical factors, it is
      suggested that the multijoint kinetic chain analysis used in the present study is
      more useful for achieving a detailed understanding of the cause of rapid kicking
      leg movement than the previously used 2-D, two-segment kinetic chain model. The
      present results also indicated that the centrifugal effect due to the kicking hip
      flexion angular velocity contributed substantially to the generation of a rapid
      knee extension, suggesting that the adjustment between the kicking hip flexion
      angular velocity and the leg configuration (knee flexion angle) is more important
      for effective instep kicking than other joint kinematics.

PMID- 20149470
TI  - New diagnosis criteria for diabetes with hemoglobin A1c and risks of macro
      vascular complications in an urban Japanese cohort: the Suita study.
AB  - The association of the new diagnosis criteria for diabetes adopting hemoglobin
      A1c, recently proposed by the international expert committee, with macro-vascular
      complications was tested in a 12-year population-based cohort. The present
      analysis suggested that this new criteria were applicable to macro-vascular
      complications in the Japanese.

PMID- 20149468
TI  - Switching cell fate: the remarkable rise of induced pluripotent stem cells and
      lineage reprogramming technologies.
AB  - Cell reprogramming, in which a differentiated cell is made to switch its fate, is
      an emerging field with revolutionary prospects in biotechnology and medicine. The
      recent discovery of induced pluripotency by means of in vitro reprogramming has
      made way for unprecedented approaches for regenerative medicine, understanding
      human disease and drug discovery. Moreover, recent studies on regeneration and
      repair by direct lineage reprogramming in vivo offer an attractive novel
      alternative to cell therapy. Although we continue to push the limits of current
      knowledge in the field of cell reprogramming, the mechanistic elements that
      underlie these processes remain largely elusive. This article reviews landmark
      developments in cell reprogramming, current knowledge, and technological
      developments now on the horizon with significant promise for biomedical
      applications.

PMID- 20149471
TI  - Six year weight change and type 2 diabetes among Australian Indigenous adults.
AB  - AIMS: To estimate weight change over 6 years among Indigenous Australian adults
      and the association with incident diabetes in north Queensland. METHODS: Baseline
      anthropometric measurements, behavioural factors, and blood samples were
      collected from 1674 Indigenous adults during 1999-2000 in 19 rural communities in
      north Queensland. Follow-up of 487 participants occurred during 2004-2007. Weight
      change was compared by age, sex, socioeconomic status, ethnicity, and behavioural
      factors. The association between weight change and diabetes incidence stratified
      by baseline BMI was studied using Cox's Proportional Hazard Model. RESULTS:
      Significantly more weight was gained among younger participants (absolute
      interval weight gain: 12.5 kg among 15-24 year olds, 5.1 kg in 25-34 year olds,
      3.4 kg in 35-44 year olds, and 1.0 kg in those over 45 years), and by those whose
      BMI was normal at baseline. Women were more likely than men to have substantial
      weight gain (43.3 vs 25.1%). Weight change was not associated with diabetes
      incidence but baseline obesity tripled the risk of developing diabetes (HR: 3.1,
      95% CI: 1.6-6.1). CONCLUSIONS: Indigenous Australian adults studied here showed
      very high levels of weight gain over a short period. Interventions aimed at
      maintaining healthy weight, particularly among young Indigenous people are
      needed.

PMID- 20149472
TI  - Fibrillar collagen scoring by second harmonic microscopy: a new tool in the
      assessment of liver fibrosis.
AB  - BACKGROUND & AIMS: Imaging of supramolecular structures by multiphoton microscopy
      offers significant advantages for studying specific fibrillar compounds in
      biological tissues. In this study, we aimed to demonstrate the relevance of
      Second Harmonic Generation (SHG) for assessing and quantifying, without staining,
      fibrillar collagen in liver fibrosis. METHODS: We first showed the relationship
      between SHG signal and collagen forms over-produced and accumulated during
      fibrosis progression. Taking this property into consideration, we developed an
      innovative method to precisely quantify the fibrosis area in histological slices
      by scoring of fibrillar collagen deposits (Fibrosis-SHG index). RESULTS: The
      scoring method was routinely applied to 119 biopsies from patients with chronic
      liver disease allowing a fast and accurate measurement of fibrosis correlated
      with the Fibrosis-Metavir score (rho=0.75, p<0.0001). The technique allowed
      discriminating patients with advanced (moderate to severe) fibrosis (AUROC=0.88,
      p<0.0001) and cirrhosis (AUROC=0.89, p<0.0001). Taking advantage of its
      continuous gradation, the Fibrosis-SHG index also allowed the discrimination of
      several levels of fibrosis within the same F-Metavir stage. The SHG process
      presented several advantages such as a high reliability and sensitivity that lead
      to a standardized evaluation of hepatic fibrosis in liver biopsies without
      staining and pathological examination. CONCLUSIONS: Second harmonic microscopy
      emerges as an original and powerful tool in the assessment of liver fibrosis and
      offers new possibilities for the evaluation of experimental protocols. We expect
      that this technology could easily be applicable in the study of other fibro
      proliferative pathologies.

PMID- 20149473
TI  - Clinical outcomes of radiofrequency ablation, percutaneous alcohol and acetic
      acid injection for hepatocelullar carcinoma: a meta-analysis.
AB  - BACKGROUND & AIMS: Radiofrequency ablation (RFA) is often the preferred local
      ablation therapy for hepatocellular carcinoma (HCC). Percutaneous ethanol
      injection (PEI) is less frequently used, and percutaneous acetic acid injection
      (PAI) has been mostly abandoned. Robust evidence showing benefit of one therapy
      versus another is lacking. Our aim was to evaluate the evidence comparing RFA,
      PEI and PAI using meta-analytical techniques. METHODS: Literature search was
      undertaken until December 2008 to identify comparative studies evaluating
      survival, recurrence, complete necrosis of tumour and complications. Only
      randomized clinical trials and quasi-randomized studies were included. Adjusted
      indirect comparisons were made when direct comparative studies were insufficient.
      RESULTS: Eight studies were identified: RFA vs. PEI (n=5), PAI vs. PEI (n=2) and
      RFA vs. PAI vs. PEI (n=1) including 1035 patients with nine comparisons. RFA was
      superior to PEI for survival (OR 0.52; 95% CI 0.35-0.78; p=0.001), complete
      necrosis of tumour and local recurrence. For tumours 2 cm RFA was not
      significantly better than PEI. PAI did not differ significantly from PEI for
      survival (OR 0.55; 95% CI 0.23-1.33; p=0.18), and local recurrence but required
      less sessions. PAI had similar outcomes, except local recurrence, to RFA in the
      direct and indirect comparison. CONCLUSIONS: RFA seems to be a superior ablative
      therapy than PEI for HCC, particularly for tumours >2 cm. PAI did not differ
      significantly from PEI for all the outcomes evaluated. RFA and PAI have similar
      survival rates. For tumours 2 cm outcome benefits comparing RFA and PEI are
      similar. PAI needs re-evaluation versus both PEI and RFA for tumours 2 cm.

PMID- 20149474
TI  - Chemotherapy with cetuximab or chemotherapy alone for untreated advanced non
      small-cell lung cancer: a systematic review and meta-analysis.
AB  - PURPOSE: To compare the efficacy and toxicities of chemotherapy plus cetuximab
      (Erbitux, E; E-chemo) with chemotherapy alone (chemo alone) in patients with
      previously untreated advanced non-small-cell lung cancer (NSCLC). The primary
      endpoint was overall survival; the secondary endpoints were progression-free
      survival, overall response rate, one-year survival and safety. METHODS: The
      PubMed database, the Cochrane Library, conference proceedings, database of
      ongoing trials and references of published trials and reviews were screened. Two
      reviewers independently assessed the quality of the trials and extracted data.
      The hazard ratios (HRs) for overall survival and progression-free survival,
      relative risks (RRs) for overall response rate and one-year survival, and odds
      ratios (ORs) for the different types of toxicity were pooled using STATA SE10.1
      package. RESULTS: Four trials involving 2018 patients with previously untreated
      NSCLC were ultimately analyzed. The pooled HR for overall survival (HR, 0.87;
      95%CI, 0.79-0.96; p=0.004) was in favor of E-chemo, which also gave rise to a
      higher overall response rate (RR, 1.19; 95%CI, 1.04-1.37; p=0.013). The analysis
      failed to show benefit of E-chemo in progression-free survival (HR, 0.91; 95%CI,
      0.83-1.00; p=0.06) and one-year survival (RR, 1.10; 95%CI, 0.98-1.26; p=0.172). E
      chemo indeed caused more grade 3/4 rash and infusion reaction (OR, 43.86; 95%CI,
      12.46-154.44; p=0.000; OR, 3.69; 95%CI, 1.89-7.25; p=0.000; respectively).
      CONCLUSION: Our data showed that the addition of cetuximab to chemotherapy would
      improve overall survival and overall response rate. It may provide new option for
      clinical treatment for untreated advanced non-small-cell lung cancer. The side
      effects of E-chemo are predictable and manageable.

PMID- 20149476
TI  - Gibberellin 20-oxidase promotes initiation and elongation of cotton fibers by
      regulating gibberellin synthesis.
AB  - Cotton is the leading natural fiber, and gibberellin (GA) is a phytohormone
      involved in the development of cotton fibers. However, it is largely unknown how
      the GA content in ovules and fibers is regulated and how the endogenous GA
      concentration affects fiber development. To address these questions, three GA 20
      oxidase homologous genes (GhGA20ox1-3) were cloned and the endogenous bioactive
      GA content in developing ovules and fibers determined by liquid chromatography
      electrospray ionization-mass spectrometry. Real-time reverse transcription PCR
      (RT-PCR) revealed that GhGA20ox1 expressed preferentially in elongating fibers
      and that the expression level varied with the endogenous GA content consistently,
      while GhGA20ox2 and GhGA20ox3 transcripts accumulated mainly in ovules. The GA
      accumulation kinetics as well as the GhGA20ox expression differed in ovules and
      the attached fibers, suggesting relatively independent GA regulation system in
      these two sites. Transgenic cotton, over-expressing GhGA20ox1, showed GA over
      production phenotypes with increased endogenous GA levels (especially GA(4)) in
      fibers and ovules. It also produced significantly more fiber initials per ovule,
      and fiber lengths was increased compared with the control, which demonstrates
      that up-regulation of the GhGA20ox1 gene promoted fiber initiation and
      elongation. Our results suggest that GA 20-oxidase is involved in fiber
      development by regulating GA levels, and corresponding genes might be employed as
      target genes for the manipulation of fiber initiation and elongation in cotton.

PMID- 20149477
TI  - Differential in vitro responses of rice cultivars to Italian lineages of the
      blast pathogen Pyricularia grisea. 2. Aromatic biosynthesis.
AB  - Phenylalanine ammonia lyase (PAL)-specific activity levels were measured in
      suspension-cultured cells of six rice cultivars following treatment with cell
      wall hydrolysates prepared from seven Pyricularia grisea strains. Early after
      elicitation, even low hydrolysate concentrations were able to induce a
      significant increase in enzyme levels. However, neither rice genotypes showing
      differential sensitivity to blast reacted differently, nor did elicitors obtained
      from various pathotypes induce different reactions. At a later stage, higher
      hydrolysate concentrations were required to trigger maximal enzyme induction.
      Also in this case, only slight variations were detected in suspension cultures of
      a given cultivar treated with different elicitors. On the contrary, highly
      significant differences were observed among plant genotypes. A clear relationship
      was evident between the mean increase in PAL activity and the overall resistance
      to blast at the plant level. This trait could therefore represent a useful tool
      in selection for increased blast tolerance.

PMID- 20149475
TI  - Butyrate in vitro immune-modulatory effects might be mediated through a
      proliferation-related induction of apoptosis.
AB  - Survival and proliferation signals are two processes closely interrelated and
      finely controlled in most cell types, whose deregulation may lead to
      carcinogenesis. In the last decade, different studies have suggested that both
      cellular functions are also intimately associated with other cellular activities
      such as differentiation and cellular activation, especially in immune cells. The
      aim of this study was to evaluate the effects of the short-chain fatty acid
      (SCFA) butyrate on the proliferation and activation state of different cell types
      involved in inflammatory bowel disease. We focused on intestinal epithelial
      cells, macrophages and T-lymphocytes, using both primary non-transformed cultures
      and established cell lines. The results showed that low concentrations of
      butyrate inhibited the proliferation of all the immune cell types tested in this
      work, whereas it only induced apoptosis in activated T-lymphocytes, non
      differentiated epithelial cells and macrophage cell lines, but not in
      differentiated epithelial cells or primary macrophages. Butyrate apoptosis
      induction was mediated by caspase-3/7 activation. This SCFA was only able to
      modify cell activation, measured as expression of inflammatory cytokines, in
      those cell types in which apoptosis was induced. In conclusion, our results
      suggest a cell type-specificity of the immune-modulatory effects of butyrate
      based on the proliferation/activation characteristic physiology of these
      processes in different cells types.

PMID- 20149478
TI  - Physiological interactions of antiauxins with auxin in roots.
AB  - The compound 4,4,4-trifluoro-3-(indole-3-)butyric acid (TFIBA) typically promotes
      root elongation but inhibits hypocotyl elongation and therefore can be described
      as antiauxin. We compared the mode of action of TFIBA with the classical
      antiauxin p-chlorophenoxyisobutyric acid (PCIB). TFIBA, more than PCIB, promoted
      primary root elongation in young flax (Linum usitatissimum) roots on plain agar,
      but inhibited root growth in older seedlings in the presence of nutrients. The
      root content of indole-3-acetic acid (IAA) after TFIBA and PCIB treatment
      increased almost two-fold. Abscisic acid was affected only by supraoptimal TFIBA,
      but increased after PCIB application. TFIBA inhibited acropetal auxin transport
      at concentrations higher than optimal for root elongation while PCIB had no
      effect. Basipetal auxin transport was promoted at less than 0.1mM but inhibited
      at 1mM TFIBA. In contrast, PCIB promoted basipetal auxin transport between 0.1
      and 0.5mM; higher concentrations had no effect. Gravitropism was promoted by
      TFIBA at concentrations optimal for growth, but inhibited by higher
      concentrations. PCIB inhibited root gravitropism in a concentration dependent
      manner. The selective effect of TFIBA on IAA but not ABA and the interference
      with auxin transport and gravicurvature indicate that the mode of action of TFIBA
      is different from that of PCIB despite similar functions.

PMID- 20149479
TI  - A novel Ca2+-activated protease from germinating Vigna radiata seeds and its role
      in storage protein mobilization.
AB  - Calcium (Ca(2+))-dependent/activated proteases make decisive cleavages in
      proteins, affecting their further degradation/activation. Few such Ca(2+)
      dependent proteases have been reported from plants, and none during germination
      related events. Seeds are woken up from their quiescent state upon imbibition of
      water. The subsequent process of germination is strongly influenced by hormones
      (mainly gibberellins) and light, with both resulting in change in intracellular
      Ca(2+). We have investigated the effect of Ca(2+) on protease activity in
      extracts prepared from dry Vigna radiata (L.) Wilczec seeds and cotyledons 4, 24,
      48 and 72h post-imbibition. Ca(2+)-activated protease activity is present at a
      very low level in dry seeds, rises with imbibition and peaks 24h post-imbibition.
      Subsequently, the activity rapidly declines, even as total protease activity
      continues to rise. Calcium activation of proteolysis was reversed by ethylene
      diamine tetraacetic acid (EDTA), ethylene glycol-bis (2-aminoethylether)
      N,N,N',N'-tetraacetic acid (EGTA), 1,10, phenanthroline, chlorpromazine and by
      beta-mercaptoethanol in a concentration-dependent manner. Protease activity was
      also inhibited by para chloro mercuribenzoate (pCMB) and l-trans-epoxysuccinyl
      leucylamido(4-guanidino) butane (E 64), while phenyl methyl sulfonyl fluoride
      (PMSF) and pepstatin did not effect Ca(2+) activation. The protease could be
      separated from the calmodulin fraction by size-exclusion chromatography, while
      retaining its ability for Ca(2+) activation, excluding the possibility of
      activation through calmodulin-based pathways. The presence of a Ca(2+)-activated
      protease in the cotyledons suggests its role in a predetermined program of
      germination involving elevation of cytosolic Ca(2+) levels during germination.
      This protease could be an important enzyme interfacing cytoplasmic signaling
      events and initiation of storage protein mobilization during seed germination.

PMID- 20149480
TI  - Gene expression analysis of volatile-rich male flowers of dioecious Pandanus
      fascicularis using expressed sequence tags.
AB  - Pandanus fascicularis is dioecious with the female plant producing a non-scented
      fruit while the male produces a flower rich in volatiles. The essential oil
      extracted from the flowers is economically exploited as a natural flavouring
      agent as well as for its therapeutic properties. Molecular dissection of this
      distinct flower for identifying the genes responsible for its aroma by way of
      expressed sequence tags (ESTs) has not been initiated in spite of its economic
      viability. A male flower-specific cDNA library was constructed and 977 ESTs were
      generated. CAP3 analysis performed on the dataset revealed 83 contigs (549 ESTs)
      and 428 singlets, thereby yielding a total of 511 unigenes. Functional annotation
      using the BLAST2GO software resulted in 1952 Gene ontology (GO) functional
      classification terms for 621 sequences. Unknown proteins were further analysed
      with InterProScan to determine their functional motifs. RNA gel blot analysis of
      26 functionally distinct transcripts potentially involved in flowering and
      volatile generation, using vegetative and reproductive tissues of both the sexes,
      revealed differential expression profiles. In addition to an overview of genes
      expressed, candidate genes with expression that are modulated predominantly in
      the male inflorescence were also identified. This is the first report on
      generation of ESTs to determine the subset of genes that can be used as potential
      candidates for future attempts aimed towards its genetic and genome analysis
      including metabolic engineering of floral volatiles in this economically
      important plant.

PMID- 20149481
TI  - H1N1 2009 influenza among healthcare workers in a tertiary care hospital in
      Thailand.

PMID- 20149482
TI  - Prevalence of carriage of meticillin-susceptible and meticillin-resistant
      Staphylococcus aureus in employees of five microbiology laboratories in The
      Netherlands.

PMID- 20149483
TI  - MRSA screening of elective surgery day-case patients.

PMID- 20149484
TI  - Blood-brain barrier impairment is functionally correlated with clinical severity
      in patients of multiple system atrophy.
AB  - Multiple system atrophy (MSA) has been regarded as a unique entity within the
      spectrum of oligodendrogliopathy. However, the pathomechanisms underlying the
      initial trigger and aggravating factors responsible for disease progression
      remain unknown. Even though the implication of blood-brain barrier (BBB)
      dysfunction has not been fully elucidated, this dysfunction may act as a modifier
      of disease progression in neurodegenerative disease. We evaluated the integrity
      of the BBB and its functional significance in patients with MSA using the
      CSF/serum albumin index (CSF-AI) and the volume transfer coefficient (K(trans))
      in dynamic contrast-enhanced MRI (DCE-MRI). CSF-AI and K(trans) values increased
      significantly in patients with MSA compared to the control (5.1 MUg vs 3.6 MUg,
      p=0.02; 0.16/mim(-1) vs 0.05/mim(-1), p=0.001, respectively). There were positive
      relationships between both CSF-AI and K(trans) and unified MSA rating scale
      (UMSARS). K(trans) in the periventricular white matter was significantly
      correlated with the volume of white matter hyperintensities among all subjects
      (r=0.58, p=0.001) and within patients with MSA (r=0.58, p=0.019), but not within
      controls (r=0.42, p>0.05). In addition, a significant positive correlation was
      detected between CSF-AI and K(trans) (r=0.81, p=0.002). Multiple linear
      regression analysis showed that only UMSARS score was a significantly independent
      predisposing factor for CSF-AI (beta=0.193, p=0.04). Our data suggest that BBB
      dysfunction is related to the underlying nature of MSA and its dysfunction is
      closely coupled to disease severity.

PMID- 20149485
TI  - Verbal memory impairment in subcortical ischemic vascular disease: a descriptive
      analysis in CADASIL.
AB  - In the elderly, the high prevalence of Alzheimer's disease neuropathology
      presents a major challenge to the investigation of memory decline in common
      diseases such as small vessel disease. CADASIL represents a unique clinical model
      to determine the spectrum of memory impairment in subcortical ischemic vascular
      dementia (SIVD). One hundred and forty CADASIL patients underwent detailed
      clinical, neuropsychological and imaging analyses. The Free and Cued Selective
      Reminding Test was used as a measure of verbal memory. Forty-four out of 140
      CADASIL patients (31.4%) presented with memory impairment according to this test.
      Eight out of 44 (18.2%) subjects with memory impairment matched the definition of
      the amnestic syndrome of hippocampal type. While alterations in spontaneous
      recall were related to the severity of subcortical ischemic lesions, the profile
      of memory impairment, particularly the sensitivity to cueing was found related to
      other factors such as hippocampal atrophy.

PMID- 20149486
TI  - Ring sign over left kidney in 99mTc DTPA renal scintigraphy.

PMID- 20149487
TI  - [Can we improve tuberculosis prevention?].

PMID- 20149488
TI  - Synthesis and anti-inflammatory evaluation of some condensed [4-(3,4
      dimethylphenyl)-1(2H)-oxo-phthalazin-2-yl]acetic acid hydrazide.
AB  - Some new 1,3,4-triazolo-, 1,3,4-oxadiazolo-, 1,3,4-thiadiazol-, and pyrazolo-3,4
      dimethylphenyl-1(2H)-oxo-phthalazine derivatives were synthesized and identified
      by IR, (1)H NMR, MS and elemental analysis. Most of the newly synthesized
      products were tested for their anti-inflammatory activities. Among them,
      compounds 11, 17b, 20, 21 and 22 are active compare to the activity of
      indomethacin.

PMID- 20149489
TI  - Synthesis and antituberculosis activity of some N-pyridyl-N'-thiazolylhydrazine
      derivatives.
AB  - In this study, new N-(1-arylethylidene)-N'-(4-arylthiazol-2-yl)hydrazine
      derivatives were synthesized and evaluated for their antituberculosis activity.
      The chemical structures of the compounds were elucidated by IR, NMR and FAB+-MS
      spectral data and Elemental Analyses. The initial screen was conducted against
      Mycobacterium tuberculosis H37Rv (ATCC 27294) in BACTEC 12B medium using the
      Microplate Alamar Blue Assay (MABA). The VERO cell cytotoxicity assay was done in
      parallel with the TB Dose Response assay. Viability was assessed using Promega's
      Cell Titer-Glo Luminescent Cell Viability Assay. Cytotoxicity was determined from
      the dose-response curve as the CC50 using a curve-fitting program. One of the
      compounds showed high activity with low toxicity.

PMID- 20149490
TI  - Synthesis of some new pyrimido[2',1':2,3]thiazolo[4,5-b]quinoxaline derivatives
      as anti-inflammatory and analgesic agents.
AB  - Treatment of 6-aminothiouracil (1) with 2,3-dichloroquinoxaline (2) in
      ethanol/TEA afforded 6-amino-2-(3-chloroquinoxalin-2-ylthio)pyrimidin-4(3H)-one
      (3), which was refluxed in DMF to give 2-aminopyrimido[2',1':2,3]thiazolo[4,5
      b]quinoxaline-4-one (4). Compound 4 was utilized as a key intermediate for the
      synthesis of a new pyrimido[2',1':2,3]thiazolo[4,5-b]quinoxaline derivatives 5
      14via the reaction with 2-chlorobenzaldehyde, 2-chlorocyclohex-1-enecarbaldehyde,
      2-chlorobenzoic acid, 2,4-dichlorobenzoic acid, 5-chloro-3-methyl-1-phenyl-1H
      pyrazole-4-carbaldehyde, 2-chloro-4,6-dimethylnicotinonitrile, alpha,beta
      unsaturated ketones and isonicotinaldehyde, respectively. The chemical structures
      of the newly synthesized compounds were characterized by IR, NMR and mass
      spectral analysis. These compounds were also screened for their analgesic and
      anti-inflammatory activities. Some of these compounds (3, 4, 9, 10 and 12-14)
      exhibited promising activities.

PMID- 20149491
TI  - CoMFA and CoMSIA studies on HIV-1 attachment inhibitors.
AB  - A series of human immunodeficiency virus type 1 (HIV-1) attachment inhibitors
      were subjected to ligand-based three-dimensional quantitative structure-activity
      relationship (3D-QSAR) studies using the comparative molecular field analysis
      (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)
      approaches. The CoMFA model yielded satisfactory statistical data with the cross
      validated q2 value of 0.589 and the non-cross-validated r2 value of 0.963. The
      cross-validated q2 value of CoMSIA Model was 0.621 and the non-cross-validated r2
      value was 0.972. From the cross-validated results, it can be seen that the CoMSIA
      model has a better predictive ability than CoMFA model. Based on the above
      results, the CoMFA and CoMSIA analyses can be used in the design of more potent
      HIV-1 attachment inhibitors.

PMID- 20149492
TI  - Phosphaisocoumarins as a new class of potent inhibitors for pancreatic
      cholesterol esterase.
AB  - Due to the importance of pancreatic cholesterol esterase (CEase) as a potential
      target in atherosclerosis and for the development of hypocholesterolemic agents,
      there are increasing interests in designing and synthesizing CEase inhibitors. In
      the present study, we prepared forty-five isocoumarin phosphorus analogues (i.e.,
      phosphaisocoumarins) and investigated the inhibition of these compounds on the
      CEase. The results showed that some phosphaisocoumarins could act as potent
      inhibitors of CEase. The most potent inhibitors, compounds 9d, 10a and 12e give
      IC50 values of 4.8 microM, 2.3 microM and 1.9 microM, respectively. The
      inhibition mechanism and kinetic characterization studies indicate that they are
      reversible competitive inhibitors.

PMID- 20149493
TI  - Synthesis and pharmacological evaluation of novel fused thiophene derivatives as
      5-HT2A receptor antagonists: molecular modeling study.
AB  - Novel derivatives of cyclopentathienopyrimidinediones 6,
      pyridothienopyrimidinediones 7, ethyl cycloheptathiophene-3-carboxylates 10,
      ethyl tetrahydrothienopyridine-3-carboxylates 11,
      tetrahydrocycloheptathienopyrimidin-4(3H)-ones 12,
      tetrahydrotriazolobenzothienopyrimidin-5(4H)-ones 17 and tetrahydro-5H
      cycloheptathienopyrimidin-4(3H)-ones 21 have been synthesized and tested for
      their 5-HT2A antagonist activity. Preliminary pharmacological studies showed that
      compounds 3-[2-[4-phenylpiperazin-1-yl]ethyl]-6,7-dihydro-5H
      cyclopenta[b]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione 6a and ethyl 2-[[4-(2
      methoxyphenyl)piperazin-1-yl]acetylamino]-4,5,6,7-tetrahydro-6-methylthieno[2,3
      c]pyridine-3-carboxylate 11d were found to be the most active molecules as 5-HT2A
      antagonists. Molecular modeling and pharmacophore prediction methodology are used
      to study the structural features required for 5-HT2A antagonist properties of the
      active compounds compared with nonactive species by means of the molecular
      mechanic method. The 2-methoxy substituent in the structure of 11d seems to be
      necessary for its full antagonistic properties. Optimal placement of basic
      nitrogen relative to the plane of thiophene core was found to have a profound
      effect on affinity and biological activity.

PMID- 20149494
TI  - Synthesis and inhibitory evaluation of cyclohexen-2-yl- and cyclohexyl
      substituted phenols and quinones to endothelial cell and cancer cells.
AB  - Alkylation of phenols with 1,3-cyclohexadiene (1) has been conducted and a series
      of cyclohexen-2-yl- and cyclohexyl-substituted phenols and quinones were screened
      against the proliferation of HUVEC and cancer cells. Phenol type as well as the
      size and occupied position of the substitute are important for the alkylating
      reaction and the inhibitory activity and selectivity of a compound. 2,5
      di(cyclohexen-2-yl)benzene-1,4-diol (25) bearing two cyclohexen-2-yl groups and 2
      tert-butyl-5-(cyclohexen-2-yl)benzene-1,4-diol (30) bearing cyclohexen-2-yl and
      tert-butyl groups exhibited good selectivity against HUVEC proliferation (IC50s
      of 2.0 and 1.4 microM, respectively) with relatively low toxicity to ccc-HPF-1.

PMID- 20149495
TI  - Synthesis and antiviral activity of new acrylamide derivatives containing 1,2,3
      thiadiazole as inhibitors of hepatitis B virus replication.
AB  - A series of new acrylamide derivatives containing 1,2,3-thiadiazole were
      synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV)
      activities in vitro. The IC50 of compounds 9b (10.4 microg/mL), 9c (3.59
      microg/mL) and 17a (9.00 microg/mL) of the inhibition on the replication of HBV
      DNA were higher than that of the positive control lamivudine (14.8 microg/mL).
      Compound 9d exhibited significant activity against secretion of HBeAg (IC50=12.26
      microg/mL).

PMID- 20149496
TI  - Synthesis of some novel 2-substituted-5-[isopropylthiazole] clubbed 1,2,4
      triazole and 1,3,4-oxadiazoles as potential antimicrobial and antitubercular
      agents.
AB  - In the present study a series of 2-substituted-5-[isopropylthiazole] clubbed
      1,2,4-triazole and 1,3,4-oxadiazole derivatives have been synthesized and
      characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. Synthesized
      compounds were evaluated for their preliminary cytotoxicity, antimicrobial and
      antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth
      dilution assay method. Antimycobacterial activity tested against M. tuberculosis
      indicated that compounds 4b and 6g exhibited twofold enhanced potency than parent
      compound 1 and the results indicate that some of them exhibited promising
      activities and they deserve more consideration as potential antitubercular
      agents. Compound 3c, 4b and 6c exhibited good or moderate antibacterial
      inhibition and compounds 3h and 7c showed excellent antifungal activity.

PMID- 20149497
TI  - Synthesis and evaluation of SQ109 analogues as potential anti-tuberculosis
      candidates.
AB  - As part of an ongoing project to develop highly potent anti-tuberculosis
      therapeutics, six SQ109 derivatives were synthesized and screened in vitro for
      their anti-tuberculosis activity against the ATCC strain H37Rv and the
      extensively drug-resistant clinical strain XDR 173. Compound 16 with an extended
      alkene chain was the most active against both strains of Mycobacterium
      tuberculosis within a MIC range of 0.5-0.25 microM. Compound 12 and SQ109 were
      potent within a MIC range of 1-0.5 microM, whilst compound 18 displayed an
      activity within the MIC range of 0.5-2 microM against both Mycobacterium
      tuberculosis strains.

PMID- 20149498
TI  - Evaluation of anti-pigmentary effect of synthetic sulfonylamino chalcone.
AB  - The 4'-(p-toluenesulfonylamino)-4-hydroxychalcone (TSAHC), which bears inhibitory
      chemotypes for both alpha-glucosidase and tyrosinase, was evaluated for
      tyrosinase activity and depigmenting ability relative to compounds designed to
      only target tyrosianse activity. TSAHC emerged to be a competitive reversible
      inhibitor of mushroom tyrosinase. More importantly, it was also able to return
      the melanin content of alpha-melanocyte stimulated by alpha-MSH to base levels
      unlike other inhibitors that only targeted tyrosinase. The Western blot for
      expression levels of proteins involved in melanogenesis showed that TSAHC
      significantly decreased three main tyrosinase related protein in melanin
      biosynthesis, tyrosinase, TRP-1 and TRP-2.

PMID- 20149499
TI  - Synthesis of substituted acridinyl pyrazoline derivatives and their evaluation
      for anti-inflammatory activity.
AB  - A rapid preparation of compounds (1-24), with the objective of discovering novel
      and potent anti-inflammatory agent. All the compounds exhibited anti-inflammatory
      and analgesic activities at the dose 50 mg/kg p.o. The compound 1-(2',4'
      Chloroacridine-9'-yl)-3-(5'-pyridine-4-yl)-(1,3,4-oxadiazol-2-yl-thiomethyl)
      pyrazole-5-one 24 showed better anti-inflammatory and analgesic activities at the
      three graded dose of 25, 50 and 100 mg/kg p.o.

PMID- 20149500
TI  - Synthesis and anti-tuberculosis activity of new hetero(Mn, Co, Ni)trinuclear
      iron(III) furoates.
AB  - New hetero(micro(3)-oxo)trinuclear iron(III) furoates with the general formulas
      [Fe(2)MO(alpha-Fur)(6)(L)(H(2)O)(2)], where L = THF (1-3), DMF (4-5), M = Mn(2+)
      (1, 4), Co(2+) (2, 5), Ni(2+) (3, 6) and [Fe(2)MO(alpha-Fur)(6)(3Cl-Py)(3)],
      where M = Mn(2+) (7), Co(2+) (8), Ni(2+) (9); have been synthesised and
      investigated by Mossbauer and IR spectroscopies. The X-ray crystal structure has
      been determined for the 4 and 8 complexes, indicating that they are related to
      the monoclinic crystal system (P2(1)/n) and have a structure typical of mu(3)-O
      bridged trinuclear iron (III) compounds. The (57)Fe Mossbauer spectra of
      microcrystalline samples of the compounds indicate the presence of high-spin iron
      (III) (S = 5/2) with a near symmetrical environments. The iron(III)-cobalt(II)
      containing compounds 2, 5 and 8 displayed MIC values between 0.83 / 4.00
      microg/mL.

PMID- 20149501
TI  - Synthesis and antiviral activity of an imidazo[1,2-a]pyrrolo[2,3-c]pyridine
      series against the bovine viral diarrhea virus.
AB  - A series of imidazo[1,2-a]pyrrolo[2,3-c]pyridines has been prepared and evaluated
      for their anti-BVDV activities in MDBK cells. From the synthesized analogues
      bearing modifications of the substituents at positions 2, 3, 7 and 8, compounds
      10a, b, 16, 24, 25 and 26 exhibited significant anti-BVDV activities.

PMID- 20149502
TI  - Can we predict successful completion of the common foundation programme at
      interview?
AB  - AIM: To gain an understanding of patterns of retention and attrition for student
      nurses on the diploma of higher education (DipHE)/bachelor of science (B.Sc.)
      (adult) on completion of the common foundation programme (CFP=year 1 of the
      programme). METHOD: A questionnaire called the "interview score sheet" (ISS)
      collected data on six cohorts from a Higher Education Institution in Scotland. At
      the initial recruitment interview each candidate was scored independently by two
      interviewers on the ISS. Successful/unsuccessful attempts of theory-based and
      practice-based modules, and any reasons for attrition were recorded throughout
      the CFP. For the purposes of this study success was defined as achieving a pass
      grade in all modules associated with year 1 of the programme. MAIN OUTCOME
      MEASURES: The study investigated the potential of the ISS in providing a reliable
      guide for student selection onto the DipHE/B.Sc. in nursing (adult) and providing
      information about the characteristics of a typical successful/unsuccessful
      student from the CFP. ANALYSIS: Statistical analysis was conducted to examine the
      correlation between the total score on the ISS, any characteristics on the ISS
      and the students' successful completion of the CFP. RESULTS: Six-hundred and
      thirty-eight students entered the CFP: 118 (18%) were unsuccessful and 520 (82%)
      were successful completers of the CFP. From the characteristics noted at
      interview on the ISS, the most reliable predictor of success was age. The total
      score achieved on the ISS was shown not to be a reliable predictor of success.
      Although not statistically significant, testing of numeracy and standard and
      content of written work may be of some value in predicting success and may
      warrant further study.

PMID- 20149503
TI  - My face, a window to communication: using creative design in learning.
AB  - Creative art as part of assessment in nursing is a powerful alternative to
      traditional methods of promoting engagement for students who have different
      learning styles, and who value engagement in creative activities. This paper
      describes an innovative assessment approach for first year nursing students which
      addressed the development of a beginning knowledge base in therapeutic
      communication as well as critical thinking and writing skills. Each student was
      asked to design a wearable mask to display an abstract interpretation of the
      therapeutic communication skills required as a nursing student, followed by a
      discussion about therapeutic nursing communication. Results from an evaluation of
      the assessment are described using Bigg's (1995) structure of observed learning
      outcome (SOLO) taxonomy. Seventy percent of students (n=35) found the new
      assessment to be an effective learning strategy. As a creative exercise, 82%
      (n=41) found the assessment to have engaged them at a personal level. More effort
      is needed for innovative assessment strategies to promote student engagement. Use
      of a creative assessment approach that incorporates art creation shows much
      promise in bridging the gap from a superficial understanding of concepts to an
      understanding characterised by deeper learning.

PMID- 20149504
TI  - Relationship between nursing students' epistemological beliefs and locus of
      control.
AB  - INTRODUCTION: The aim of this study was to determine the relationship between
      nursing students' epistemologic beliefs and locus of control, and the research
      was conducted at Istanbul University Florence Nightingale School of Nursing with
      350 nursing students. METHODS: Data were collected using the Turkish version of
      the Epistemological beliefs questionnaire and Rotter's Internal-External Locus of
      Control Scale. In the data analysis number, percentage, mean, correlation
      analysis, one-way analysis of variance and Tukey HSD test were used. RESULTS: The
      findings as whole indicated that nursing students' epistemological beliefs that
      "The Belief of Learning Depends on Effort (Effort)" showed a greater degree of
      development than their beliefs about the two other dimensions as named "The
      Belief of Learning Depends on Ability (Ability)" and "The Belief That There is
      Only One Unchanging Truth (Unchanging Truth)" in this study, while their belief
      that there is Unchanging Truth was not developed when compared to the other two.
      There was a positive correlation between nursing students locus of control and
      Effort and Ability dimensions, but a significant correlation was not found with
      Unchanging Truth dimension. CONCLUSION: This researcher suggests that research
      should be carried out to determine nursing students' epistemological beliefs and
      the factors influencing them in an environment to promote the development of
      these beliefs, and thus the research can be used to learn about the development
      of the epistemological beliefs.

PMID- 20149505
TI  - The influence of the axial, antero-posterior and lateral positions of the center
      of rotation of a ball-and-socket disc prosthesis on the cervical spine
      biomechanics.
AB  - BACKGROUND: Previous studies documented the importance of the positioning and the
      design parameters of the prosthesis in determining the biomechanics of the
      implanted spine. However, a comprehensive biomechanical evaluation of the
      significance of these parameters is still lacking. Therefore, the paper is aimed
      to the quantification of their influence on the flexibility of the implanted
      spine and the force transmitted through the facet joints. METHODS: A finite
      element model of the C5-C6 spine unit including a ball-and-socket disc prosthesis
      was built. Three probabilistic variables were considered: the axial, antero
      posterior and lateral positions of the center of rotation. Randomized input
      parameters were generated with the Monte Carlo method. Pure moments of 1.6 Nm in
      flexion, extension, lateral bending and axial rotation were imposed to the upper
      endplate of C5; 100 simulations were conducted for the each of the considered
      loading conditions. FINDINGS: Axial position of the center of rotation influenced
      the spine flexibility in all loading conditions and the facet force in extension,
      lateral bending and axial rotation. The antero-posterior position was found to
      influence the spine flexibility in flexion and extension, and the facet force in
      lateral bending and axial rotation. The lateral position was not significant.
      INTERPRETATION: The effects of the positioning of a cervical disc prosthesis were
      estimated. A wide range of mechanical behaviors can be obtained by the
      manufacturers by appropriately manipulating the position of the center of
      rotation. A proper positioning of the artificial disc during the surgery, in
      particular in the antero-posterior direction, was found to be of critical
      importance.

PMID- 20149506
TI  - Terricolous alpine lichens are sensitive to both load and concentration of
      applied nitrogen and have potential as bioindicators of nitrogen deposition.
AB  - The influence of applied nitrogen (N) concentration and load on thallus chemistry
      and growth of five terricolous alpine lichen species was investigated in a three
      month N addition study. Thallus N content was influenced by both concentration
      and load; but the relative importance of these parameters varied between species.
      Growth was most affected by concentration. Thresholds for effects observed in
      this study support a low critical load for terricolous lichen communities (<7.5
      kg N ha(-1) y(-1)) and suggest that concentrations of N currently encountered in
      UK cloudwater may have detrimental effects on the growth of sensitive species.
      The significance of N concentration effects on sensitive species also highlights
      the need to avoid artificially high concentrations when designing N addition
      experiments. Given the sensitivity of some species to extremely low loads and
      concentrations of N we suggest that terricolous lichens have potential as
      indicators of deposition and impact in northern and alpine ecosystems.

PMID- 20149507
TI  - Decomposing cross-country differences in levels of obesity and overweight: does
      the social environment matter?
AB  - This paper examines the influence of environmental factors on weight gain and
      obesity. We take advantage of a markedly different pattern of obesity between
      Italy in Spain to undertake a non-linear decomposition analysis of differences in
      the prevalence of overweight and obesity between the two countries. The analysis
      is based on cross-sectional national surveys for 2003. We have attempted to
      isolate the influence of lifestyle factors, socio-economic and socio
      environmental effects in explaining cross-country differences in BMI status. Our
      findings suggest that when the social environment (proxied by different measures
      of peer effects and regional BMI) is not controlled for, we explain about 27-42%
      of the overall Spain-to-Italy overweight and obesity gap. Differences in eating
      habits and education between the two countries are the main predictors of the
      gaps in obesity and overweight. However, when social environment is controlled
      for, our estimates explain between 76 and 92% of the obesity and overweight gap
      and the effect of eating habits are wiped out. These results suggest healthy body
      weight depends on cultural or environmental triggers that operate through
      individual level health production determinants.

PMID- 20149508
TI  - Endoscopic observation and strategic management of obstructive submandibular
      sialadenitis.
AB  - PURPOSE: Obstructive submandibular sialadenitis is a relatively common disease in
      the clinic. The present study explored the cause and strategic management of
      chronic obstructive sialadenitis using sialoendoscopy and surgery. PATIENTS AND
      METHODS: From January 2005 to October 2007, 128 patients with obstructive
      symptoms in the submandibular gland were diagnosed using sialoendoscopy and
      occlusal films, and the obstructions were removed using interventional
      sialoendoscopy, surgery only, or combined techniques, depending on the size,
      shape, site, and quality of the sialolith in the duct. The shape and structure of
      the hilus of the submandibular gland was observed using sialoendoscopy. RESULTS:
      In the submandibular gland, the histologic features of 128 cases were identified
      endoscopically and radiographically. The endoscopic findings were of 3 types:
      sialolith in 114 (89%), mucus plug in 8 (6%), and stenosis in 6 (5%). Of 51
      obstructions treated surgically, 47 were removed successfully, for a success rate
      of 92%. Of 63 obstructions treated using interventional sialoendoscopy, 52 were
      removed directly by sialoendoscopy, for a success rate of 83%. The unsuccessful
      cases were treated using sialoendoscopy or surgery. The obstructive symptoms were
      relieved in 12 of 14 patients without stones using dilation and irrigation under
      sialoendoscopy. Of the 114 patients with a stone, the sialoliths of 67 (59%) were
      located in the distal region (behind the first molar). The results showed that
      the more posterior the stone, the more difficult it was to remove. Three patients
      with treatment failure ultimately underwent resection of the gland. A basin-like
      structure in the hilus region was found in 86 (67%) of the 128 patients by
      sialoendoscopy. Finally, 5 patients were found to have a foreign body (fish bone)
      surrounded by a sialolith. CONCLUSIONS: Sialoendoscopy is a useful new technique,
      not to only detect the cause of obstruction in a submandibular gland, but also to
      treat the obstructive submandibular sialadenitis more effectively if incorporated
      with conventional surgical approaches.

PMID- 20149509
TI  - Evaluation of temporomandibular function after high partial condylectomy because
      of unilateral condylar hyperactivity.
AB  - PURPOSE: The purpose of this study was to assess temporomandibular function after
      condylectomy because of unilateral condylar hyperactivity (UCH) by means of
      standardized diagnostic criteria. The results were compared with those obtained
      in a control group. PATIENTS AND METHODS: In this study, 33 patients with UCH who
      underwent condylectomy and 31 controls matched for age and gender filled out a
      history questionnaire and underwent a clinical examination as part of the
      research diagnostic criteria for temporomandibular disorders. Data analysis was
      performed by use of the Fisher exact test for 2-by-2 tables. RESULTS: Patients
      and controls did not differ significantly regarding myofacial pain (P = .131),
      disc displacement (P = .516), and depression (P = .34). The groups differed
      significantly concerning arthralgia, osteoarthritis, and osteoarthrosis (P =
      .003), as well as pain with low disability (P = .022). CONCLUSIONS: In patients
      with UCH who underwent condylectomy because of progressive mandibular asymmetry,
      more joint-related temporomandibular problems as well as more postoperative pain
      developed when compared with age- and gender-matched controls. However, these
      problems did not lead to more severe disabilities in daily life.

PMID- 20149510
TI  - Osteonecrosis of the jaw in a patient on Denosumab.

PMID- 20149511
TI  - Increased levels of soluble cytokine receptors in the synovial fluid of
      temporomandibular joint disorders in relation to joint effusion on magnetic
      resonance images.
AB  - PURPOSE: The purpose of this study is to clarify the significance of joint
      effusion (JE) on T2-weighted magnetic resonance images of the temporomandibular
      joint (TMJ) in comparison to various soluble cytokine receptors in the synovial
      fluid of patients with temporomandibular disorders (TMDs). PATIENTS AND METHODS:
      Magnetic resonance imaging of 55 TMJs of 55 patients with TMD was performed, and
      synovial fluid samples were obtained on the same day. The grade of JE was
      evaluated on a scale from 0 to 3, with grade 0 indicating the absence of JE and
      grades 1 to 3 indicating the presence of JE. Correlations were measured between
      JE and the concentrations of soluble tumor necrosis factor receptors I and II,
      interleukin (IL) 6 soluble receptor, IL-1 soluble receptor type II, and IL-1
      receptor antagonist and protein in the synovial fluid samples. RESULTS: The mean
      concentrations of cytokine receptors in the synovial fluid were significantly
      higher in the 30 joints with JE than in the 25 joints without JE. There were no
      correlations between the JE grade and the level of any mediators. CONCLUSION:
      Increased levels of cytokine receptors are likely to influence the expression of
      JE and may play important roles in the pathogenesis of TMD. These results also
      suggest that JE may reflect synovial inflammation of the TMJ.

PMID- 20149512
TI  - Representational momentum in children born preterm and at term.
AB  - The term representational momentum (RM) refers to the idea that our memory
      representations for moving objects incorporate information about movement - a
      fact that can lead us to make errors when judging an object's location (the RM
      effect). In this study, we explored the RM effect in a sample of children born
      very prematurely and a sample born at term. Because preterm children are known to
      be at risk for problems with motion perception, we anticipated that they would
      show a weaker or absent RM effect. This prediction was confirmed. In addition, we
      found that, in both samples of children, 5-6year olds showed a reduced RM effect
      compared to 7-9year olds. These results demonstrate that the ability to represent
      motion information in memory shows continued development over this age range, and
      may help to elucidate factors contributing to problems with fine and gross motor
      planning and execution that have been observed in the preterm population. We
      propose that problems affecting the formation, maintenance, or use of predictive
      models, or motion extrapolation skills, may have cascading effects on the
      development of other abilities.

PMID- 20149513
TI  - [Old methods, new applications].

PMID- 20149514
TI  - Post-resuscitative clinical features in the first hour after achieving sustained
      ROSC predict the duration of survival in children with non-traumatic out-of
      hospital cardiac arrest.
AB  - AIM OF THE STUDY: Although sustained return of spontaneous circulation (ROSC) can
      be initially established after resuscitation from non-traumatic out-of-hospital
      cardiac arrest (OHCA) in some children, many of the children lose spontaneous
      circulation during hospital stay and do not survive to discharge. The aim of this
      study was to determine the clinical features during the first hour after ROSC
      that may predict survival to hospital discharge. METHODS: We retrospectively
      evaluated the medical records of 228 children who presented to the emergency
      department without spontaneous circulation following non-traumatic OHCA during
      the period January 1996 to December 2008. Among these children, 80 achieved
      sustained ROSC for at least 20 min. The post-resuscitative clinical features
      during the first hour after achieving sustained ROSC that correlated with
      survival, median duration of survival, and death were analyzed. RESULTS: Among
      the 80 children who achieved sustained ROSC for at least 20 min, 28 survived to
      hospital discharge and 6 had good neurologic outcomes (PCPC scale=1 or 2). Post
      resuscitative clinical features associated with survival included sinus cardiac
      rhythm (p=0.012), normal heart rate (p=0.008), normal blood pressure (p<0.001),
      urine output>1 ml/kg/h (p=0.002), normal skin color (p=0.016), lack of
      cardiopulmonary resuscitation (CPR)-induced rib fracture (p=0.044), initial
      Glasgow Coma Scale score>7 (p<0.001), and duration of in-hospital CPR<or=10 min
      (p<0.001). Furthermore, these variables were also significantly associated with
      the duration of survival (all p<0.05). CONCLUSIONS: The most important predictors
      of survival to hospital discharge in children with OHCA who achieve sustained
      ROSC are a normal heart rate, normal blood pressure, and an initial urine
      output>1 ml/kg/h.

PMID- 20149515
TI  - The role of bystanders during rescue and resuscitation of drowning victims.
AB  - BACKGROUND: Bystanders make a critical difference in the survival of drowning
      victims. Little information on their role before arrival of the Emergency Medical
      Services (EMS) is available in the scientific literature. In a descriptive study,
      this role is investigated. METHODS AND RESULTS: We studied 289 rescue reports
      (1999-2004) available from the Dutch Maatschappij tot Redding van Drenkelingen
      (Society to Rescue People from Drowning), an organisation that, since 1767,
      acknowledges awards to bystanders who have contributed to the survival of a
      drowning victim. There were 138 variables retrieved from these reports. The
      Utstein Style for Drowning (USFD) was used as a guideline. Of the 26 USFD
      parameters on victim and scene information, 21 were available for analysis. Eight
      non-USFD parameters, defined by the authors of this research, were available in
      >60% of the cases. There were 343 victims, rescued by 503 rescuers. 109 victims
      were resuscitated by bystanders. Of the 18 victims who first received
      resuscitation from bystanders and then consequently from pre-hospital
      professionals, 14 survived. Rescues often occurred in dangerous circumstances:
      multiple victims (n=90/343), cold or ice-cold water (n=295/341), deep water
      (n=316/334), swimming to the victims (n=262/376), young age of rescuers (the
      youngest rescuer was 5 years of age). CONCLUSIONS: Bystander rescue and
      resuscitation of drowning victims seems to contribute to a positive outcome.
      Bystanders are prepared to take responsibility to rescue a drowning victim in
      spite of significant dangers. The USFD is helpful in understanding the role of
      bystanders in drowning situations, but may need modification to become more
      instrumental.

PMID- 20149517
TI  - A paediatric cardiopulmonary resuscitation training project in Honduras.
AB  - OBJECTIVES: It is possible that the exportation of North American and European
      models has hindered the creation of a structured cardiopulmonary resuscitation
      (CPR) training programme in developing countries. The objective of this paper is
      to describe the design and present the results of a European paediatric and
      neonatal CPR training programme adapted to Honduras. MATERIALS AND METHODS: A
      paediatric CPR training project was set up in Honduras with the instructional and
      scientific support of the Spanish Group for Paediatric and Neonatal CPR. The
      programme was divided into four phases: CPR training and preparation of
      instructors; training for instructors; supervised teaching; and independent
      teaching. RESULTS: During the first phase, 24 Honduran doctors from paediatric
      intensive care, paediatric emergency and anaesthesiology departments attended the
      paediatric CPR course and 16 of them the course for preparation as instructors.
      The Honduran Paediatric and Neonatal CPR Group was formed. In the second phase,
      workshops were given by Honduran instructors and four of them attended a CPR
      course in Spain as trainee instructors. In the third phase, a CPR course was
      given in Honduras by the Honduran instructors, supervised by the Spanish team. In
      the final phase of independent teaching, eight courses were given, providing 177
      students with training in CPR. CONCLUSIONS: The training of independent
      paediatric CPR groups with the collaboration and scientific assessment of an
      expert group could be a suitable model on which to base paediatric CPR training
      in Latin American developing countries.

PMID- 20149516
TI  - "Identifying the hospitalised patient in crisis"--a consensus conference on the
      afferent limb of rapid response systems.
AB  - BACKGROUND: Most reports of Rapid Response Systems (RRS) focus on the efferent,
      response component of the system, although evidence suggests that improved vital
      sign monitoring and recognition of a clinical crisis may have outcome benefits.
      There is no consensus regarding how best to detect patient deterioration or a
      clear description of what constitutes patient monitoring. METHODS: A consensus
      conference of international experts in safety, RRS, healthcare technology,
      education, and risk prediction was convened to review current knowledge and
      opinion on clinical monitoring. Using established consensus procedures, four
      topic areas were addressed: (1) To what extent do physiologic abnormalities
      predict risk for patient deterioration? (2) Do workload changes and their
      potential stresses on the healthcare environment increase patient risk in a
      predictable manner? (3) What are the characteristics of an "ideal" monitoring
      system, and to what extent does currently available technology meet this need?
      and (4) How can monitoring be categorized to facilitate comparing systems?
      RESULTS AND CONCLUSIONS: The major findings include: (1) vital sign aberrations
      predict risk, (2) monitoring patients more effectively may improve outcome,
      although some risk is random, (3) the workload implications of monitoring on the
      clinical workforce have not been explored, but are amenable to study and should
      be investigated, (4) the characteristics of an ideal monitoring system are
      identifiable, and it is possible to categorize monitoring modalities. It may also
      be possible to describe monitoring levels, and a system is proposed.

PMID- 20149518
TI  - Treatment of landfill leachates by nanofiltration.
AB  - Landfill leachate contains high concentrations of organic matter, color, heavy
      metals and toxic substances. This study presents the feasibility of a commercial
      nanofiltration membrane (NF-300) in the removal of pollutants from a landfill
      leachate generated from the Treatment Stabilization and Disposal Facility in
      Gujarat state of India. Two different leachate samples (Leachates A and B) were
      collected from the downstream side of closed landfill cells A and B. The average
      quality of the leachate was 67 719 mg/L COD, 217 mg/L ammonical nitrogen, 22 418
      mg/L BOD, 3847 mg/L chlorides and 909 mg/L sulphate. The operating variables
      studied were applied pressure (4-20 atm), feed flowrate (5-15L/min) and pH (2, 4,
      5.5 and 6.7). It was observed that the solute rejection (R(O)) increased with
      increase in feed pressure and decreased with increase in feed concentration at
      constant feed flowrate. In the present study, the rejection of cations followed
      the sequence: R(O) (Cr(3+))>R(O) (Ni(2+))>R(O) (Zn(2+))>R(O) (Cu(2+))>R(O)
      (Cd(2+)) for leachates A and B. The order of solute rejection sequence is
      inversely proportional to the diffusion coefficients. The rejection of sulphate
      ions by the NF-300 membrane was 83 and 85%, while the rejection of chlorides was
      62 and 65% for leachates A and B, respectively. The NF-300 membrane was
      characterized by using the combined-film theory-Spiegler-Kedem (CFSK) model based
      on irreversible thermodynamics and the ion transport model based on the extended
      Nernst-Planck equation. The membrane transport parameters were estimated using
      the Levenberg-Marquadt method. The estimated parameters were used to predict the
      membrane performance and the predicted values are in good agreement with the
      experimental results.

PMID- 20149519
TI  - A multi-period optimization model for energy planning with CO(2) emission
      consideration.
AB  - A novel deterministic multi-period mixed-integer linear programming (MILP) model
      for the power generation planning of electric systems is described and evaluated
      in this paper. The model is developed with the objective of determining the
      optimal mix of energy supply sources and pollutant mitigation options that meet a
      specified electricity demand and CO(2) emission targets at minimum cost. Several
      time-dependent parameters are included in the model formulation; they include
      forecasted energy demand, fuel price variability, construction lead time,
      conservation initiatives, and increase in fixed operational and maintenance costs
      over time. The developed model is applied to two case studies. The objective of
      the case studies is to examine the economical, structural, and environmental
      effects that would result if the electricity sector was required to reduce its
      CO(2) emissions to a specified limit.

PMID- 20149520
TI  - Kinetic development and evaluation of membrane sequencing batch reactor (MSBR)
      with mixed cultures photosynthetic bacteria for dairy wastewater treatment.
AB  - This experimental study was conducted to evaluate a membrane sequencing batch
      reactor (MSBR) with mixed culture photosynthetic bacteria for dairy wastewater
      treatment. The study was undertaken in two steps: laboratory and pilot scale
      experiments. In the first step, kinetics analysis of the MSBR was carried out in
      a laboratory scale experiment with influent COD concentration of 2500 mg/L. The
      pilot scale experiment was conducted to investigate the performance of the MSBR
      and checked the suitability of the kinetics for an engineering design. The
      kinetic coefficients K(s), k, k(d), Y and mu(m) were found to be 174-mg-COD/L,
      7.42/d, 0.1383/d, 0.2281/d and 1.69/d, respectively. There were some deviations
      of COD removal efficiency between the design value and the actual value. From the
      kinetics estimation, COD effluent from the design was 27 mg/L while the average
      actual COD effluent from the experiment was 149 mg/L. Due to the different light
      source condition, the factors relating to light energy (i.e. L(f) and IR(%)) must
      be incorporated into engineering design and performance prediction with these
      kinetic coefficients of the photosynthetic MSBR.

PMID- 20149521
TI  - Should urologists always perform a bladder cuff resection during
      nephroureterectomy, and which method should they use?

PMID- 20149523
TI  - Alpha-fetoprotein producing cells act as cancer progenitor cells in human
      cholangiocarcinoma.
AB  - We aimed to demonstrate that alpha-fetoprotein (AFP)-producing cells in
      cholangiocarcinomas possessed cancer stem cell (CSC)-like properties. AFP
      enhancer/promoter-driven EGFP gene was transfected into human cholangiocarcinoma
      cell lines. One cell line, RBE, expressed both AFP and EGFP. Clonal analyses
      revealed that one EGFP-positive cell generated both EGFP-positive and EGFP
      negative cell fractions. However, one EGFP-negative cell never produced EGFP
      positive cells. The EGFP-positive cells had a greater tumorigenic potential. Only
      the EGFP-positive cells expressed Notch1. AFP and Notch1 expression was observed
      in clinical intrahepatic cholangiocarcinomas. The AFP-producing cells were
      suggested to be CSCs. The Notch pathway might play an important role in
      maintaining the CSC characteristics.

PMID- 20149524
TI  - Anti-tumor immune response induced by dendritic cells transduced with truncated
      PSMA IRES 4-1BBL recombinant adenoviruses.
AB  - Up-regulation of receptor-ligand pairs during interaction of a peptide-bound MHC
      complex on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive
      diversity in the ensuing T cell immune response. Members of the TNF ligand
      superfamily and the TNFR superfamily contribute to this costimulatory molecule
      signaling. In the present study, we used replication deficient adenoviruses to
      introduce a tumor-associated Ag (a truncated human prostate-specific membrane
      antigen (tPSMA)) and the T cell costimulatory molecule 4-1BBL into murine DCs,
      and observed the ability of these recombinant DCs to elicit tPSMA-directed T-cell
      responses in vitro and anti-tumor immunity to RM-1-tPSMA in a murine tumor model.
      Infection of DCs with Ad-tPSMA-IRES-m4-1BBL induced tPSMA-specific proliferative
      responses and up-regulated CD80 and CD86 s signaling molecules. The cytotoxic T
      lymphocytes activated by the Ad-tPSMA-IRES-m4-1BBL-transfected DCs showed
      significantly higher IFN-gamma production and cytotoxicity against the RM-1 cells
      transfected with tPSMA. Moreover, vaccination of mice with Ad-tPSMA-IRES-m4-1BBL
      transfected DCs induced a potent protective and therapeutic anti-tumor immunity
      to RM-1-tPSMA in a tumor model. These results demonstrated that development of
      DCs engineered to express tPSMA and 4-1BBL by recombinant adenovirus-mediated
      gene transfer may offer a new strategy for prostate cancer immunotherapy.

PMID- 20149525
TI  - Part 1. Spectrophotometric determination of trace mercury (II) in dental-unit
      wastewater and fertilizer samples using the novel reagent 6-hydroxy-3-(2
      oxoindolin-3-ylideneamino)-2-thioxo-2H-1,3-thiazin-4(3H)-one and the dual
      wavelength beta-correction spectrophotometry.
AB  - A simple and low cost method was developed and validated for the determination of
      trace mercury (II) ions in dental-unit wastewater and fertilizer samples. The
      method was based upon the reaction of mercury (II) ions with the novel reagent 6
      hydroxy-3-(2-oxoindolin-3-ylideneamino)-2-thioxo-2H-1,3-thiazin-4(3H)-one, the
      formed complex shows an absorption maximum at 505 nm (lambda(max)) in Britton
      Robinson (B-R) buffer (pH 4-6).The corrected absorbance of the formed complex at
      lambda(max) was obtained employing beta-correction spectrophotometric method.
      Beer's-Lambert law and Ringbom's plots of the colored Hg-reagent complex were
      obeyed in the concentration range of 0.2-2.0 and 0.32-0.96 microg mL(-1) mercury
      (II) ions, respectively with a relative standard deviation in the range of 2.1+/
      1.3%. The limits of detection (LOD) and quantification (LOQ) of the procedure
      were 0.026 and 0.086 microg mL(-1) Hg(2+), respectively. The proposed method was
      applied for the analysis of mercury (II) in dental-unit wastewater and fertilizer
      samples. The validation of the method was tested by comparison with the data
      obtained by the inductively coupled plasma-mass spectrometry (ICP-MS). The
      statistical treatment of data in terms of Student's t-tests and variance ratio f
      tests has revealed no significance differences.

PMID- 20149526
TI  - Catalytic oxidation and spectroscopic analysis of simulated wastewater containing
      o-chlorophenol by using chlorine dioxide as oxidant.
AB  - The activated carbon-MnO(2) catalyst has been prepared by the dipping-calcination
      method with activated carbon used as a carrier. The catalyst is used for
      catalyzing/degrading simulated o-chlorophenol wastewater with chlorine dioxide as
      oxidant. The COD removal efficiency by catalytic oxidation is 93.5% at the
      condition of wastewater's COD is 2085 mg/l, the pH value is 1.2, the dosage of
      chlorine dioxide is 1000 mg/l, the dosage of activated carbon-MnO(2) catalyst is
      6g by reacting 60 min. The COD removal efficiency by catalytic oxidation is great
      than that of chemical oxidation. The catalytic activity of the catalyst only
      decreased a small amount in terms of COD removal efficiency after using 11 times.
      The COD removal efficiency is 80-90% during the continuity wastewater treatment
      experiment, which indicates that the wastewater treatment process is practical.
      The FTIR spectra indicate that the active ingredient of manganese dioxide is
      linked with activated carbon by chemical bond, not merely mechanical blending.

PMID- 20149527
TI  - Study of the behaviour of different NF membranes for the reclamation of a
      secondary textile effluent in rinsing processes.
AB  - More demanding legal regulations for the wastewater disposal and water scarcity
      make necessary wastewater reuse in the industry. In particular, textile industry
      generates large amounts of wastewater with a high concentration of pollutants.
      Even though present biological or physical-chemical treatments are broadly in
      place, the quality of the final effluent is not good enough to allow its direct
      reuse. Consequently, a complementary membrane process is required in order to
      improve wastewater characteristics. In this work, six NF membranes were tested at
      different volume concentration factors in order to select the most appropriate
      one. The main studied criteria were the permeate quality for its reuse in the
      textile processes and the minimum membrane fouling effect. The different results
      obtained for the tested membranes were explained by membrane characterization
      parameters as contact angle, roughness and size exclusion. Taking these factors
      into consideration, TFC-SR2 has shown the overall best results because of the
      high permeate flux and the minimum fouling (in terms of the normalised flux
      reduction).

PMID- 20149528
TI  - Adsorption kinetics and desorption of Cu(II) and Zn(II) from aqueous solution
      onto humic acid.
AB  - The adsorption kinetics of Cu(II) and Zn(II) from aqueous solution onto humic
      acid (HA) were investigated under different conditions. The results showed that
      HA was particularly effective for adsorbing heavy metals and that the effective
      pH range was above 6. The adsorption force was not single and dependent on
      solution pH. The experimental data were found to comply with the pseudo-second
      order kinetic model with adsorption capacity, q(e cal) more close to the measured
      results. Increment of initial adsorbate concentration (1-4 mg/L) and temperature
      (283-303 K) are both favorable to adsorption process. Based on the desorption
      experiments, it is further indicated that the main adsorption force was
      complexation effect between organic ligands of HA surface and metal ions and the
      percentage of desorption is 50% for Cu and 30% for Zn, respectively.

PMID- 20149529
TI  - Synthesis and the effect of calcination temperature on the physical-chemical
      properties and photocatalytic activities of Ni,La codoped SrTiO3.
AB  - A series of highly vis-light active Ni,La-codoped SrTiO(3) photocatalysts were
      successfully synthesized with sol-gel process. The characterization results show
      that the calcination temperature has a strong influence on the physical-chemical
      properties of as-synthesized photocatalysts. The surface area and porosity, even
      the initial adsorption rate for malachite green (MG), decreased with increasing
      calcination temperature. To evaluate the photocatalytic activities, the
      photodegradation of a water contaminant (MG) was carried out under visible light
      irradiation. The as-synthesized photocatalysts exhibited a high vis-light
      activity, and a 100% degradation of MG was observed for the Ni,La-SrTiO(3)-x
      catalysts calcined at low temperature under visible light irradiation for 1h,
      during which only 7% and 15% of MG was degraded for self-degrade and commercially
      available photocatalyst Degussa P25, respectively. The high vis-light activity is
      a result of the best combination of many properties, such as the intensive
      visible light response, the large surface area and pore volume and the high
      initial adsorption rate for substrate.

PMID- 20149530
TI  - A simple method for screening emission sources of carbonyl compounds in indoor
      air.
AB  - Volatile organic compounds (VOCs) emitted from building and furnishing materials
      are frequently observed in high concentrations in indoor air. Nondestructive
      analytical methods that determine the main parameters influencing concentration
      of the chemical substances are necessary to screen for sources of VOC emissions.
      Toward this goal, we have developed a new flux sampler, referred to herein as an
      emission cell for simultaneous multi-sampling (ECSMS), that is used for screening
      indoor emission sources of VOCs and for determining the emission rates of these
      sources. Because the ECSMS is based on passive sampling, it can be easily used on
      site at a low cost. Among VOCs, low-molecular-weight carbonyl compounds including
      formaldehyde are frequently detected at high concentrations in indoor
      environments. In this study, we determined the reliability of the ECSMS for the
      collection of formaldehyde and other carbonyl compounds emitted from wood-based
      composites of medium density fiberboards and particleboards. We then used
      emission rates determined by the ECSMS to predict airborne concentrations of
      formaldehyde emitted from a bookshelf in a large chamber, and these data were
      compared to formaldehyde concentrations that were acquired simultaneously by
      means of an active sampling method. The values obtained from the two methods were
      quite similar, suggesting that ECSMS measurement is an effective method for
      screening primary sources influencing indoor concentrations of formaldehyde.

PMID- 20149531
TI  - Synthesis and characterization of La2O3/TiO2-xFx and the visible light
      photocatalytic oxidation of 4-chlorophenol.
AB  - In this work, we investigated the synergetic effect of La and F on the visible
      light photocatalytic activity of TiO(2) catalysts. La(2)O(3)/TiO(2-x)F(x)
      photocatalysts were prepared by a simple sol-gel process using tetrabutyl
      titanate (TBT), La(NO(3))(3) and NH(4)F as precursors. XPS results revealed that
      La(2)O(3) accumulated on the surface of TiO(2), which enhanced the surface area
      of TiO(2) and inhibited the recombination of electron-hole pairs. It also showed
      that two kinds of fluorine species were formed and these increased the acid
      active sites and enhanced the oxidation potential of the photogenerated holes in
      the valance band. UV-vis diffuse reflection spectra of La(2)O(3)/TiO(2-x)F(x)
      showed that intraband gap states were present and these are probably responsible
      for its absorption of visible light while the intrinsic absorption band was
      shifted slightly to a longer wavelength. At molar ratios of La and F to Ti of
      1.5:100 and 5:100 and after calcination at 500 degrees C, the degradation rate of
      4-chlorophenol (4-CP) over the sample was about 1.2-3.0 times higher than that of
      the other doped samples and undoped TiO(2). The total organic carbon (TOC)
      removal rates of 4-CP showed that 4-CP was mineralized efficiently in the
      presence of the sample under visible light illumination.

PMID- 20149532
TI  - Toxicity of carbon nanotubes to the activated sludge process.
AB  - The discharge of carbon nanotubes (CNTs) from industrial waste or disposal of
      such materials from commercial and/or domestic use will inevitably occur with
      increasing production and enter into wastewater treatment facilities with unknown
      consequences. Therefore, a better knowledge of the toxicity of CNTs to biological
      processes in wastewater treatment will be critical. This study examined the
      toxicity of multi-walled carbon nanotubes (MWCNTs) on the microbial communities
      in activated sludge. A comparative study using the activated sludge respiration
      inhibition test was performed on both unsheared mixed liquor and sheared mixed
      liquor to demonstrate the potential toxicity posed by MWCNTs and to illustrate
      the extent of extracellular polymeric substances (EPS) in protecting the
      microorganisms from the toxicity of CNTs. Respiration inhibition was observed for
      both unsheared and sheared mixed liquor when MWCNTs were present, however,
      greater respiration inhibition was observed for the sheared mixed liquor. The
      toxicity observed by the respiration inhibition test was determined to be dose
      dependent; the highest concentration of MWCNTs exhibited the highest respiration
      inhibition. Scanning Electron Microscopy (SEM) images demonstrated direct
      physical contact between MWCNTs and activated sludge flocs.

PMID- 20149533
TI  - Thiosulfate leaching of gold from waste mobile phones.
AB  - The present communication deals with the leaching of gold from the printed
      circuit boards (PCBs) of waste mobile phones using an effective and less
      hazardous system, i.e., a copper-ammonia-thiosulfate solution, as an alternative
      to the conventional and toxic cyanide leaching of gold. The influence of
      thiosulfate, ammonia and copper sulfate concentrations on the leaching of gold
      from PCBs of waste mobile phones was investigated. Gold extraction was found to
      be enhanced with solutions containing 15-20 mM cupric, 0.1-0.14 M thiosulfate,
      and 0.2-0.3 M ammonia. Similar trends were obtained for the leaching of gold from
      two different types of scraps and PCBs of waste mobile phones. From the scrap
      samples, 98% of the gold was leached out using a solution containing 20 mM
      copper, 0.12 M thiosulfate and 0.2 M ammonia. Similarly, the leaching of gold
      from the PCBs samples was also found to be good, but it was lower than that of
      scrap samples in similar experimental conditions. In this case, only 90% of the
      gold was leached, even with a contact time of 10h. The obtained data will be
      useful for the development of processes for the recycling of gold from waste
      mobile phones.

PMID- 20149534
TI  - Combined advanced oxidation processes for the synergistic degradation of
      ibuprofen in aqueous environments.
AB  - Ibuprofen (IBP) is a widely used analgesic and anti-inflammatory drug and has
      been found as a pollutant in aqueous environments. The sonolytic, photocatalytic
      and sonophotocatalytic degradations of IBP in the presence of homogeneous
      (Fe(3+)) and heterogeneous photocatalysts (TiO(2)) were studied. When compared
      with sonolysis and photocatalysis, a higher degradation rate was observed for
      sonophotocatalysis in the presence of TiO(2) or Fe(3+) and also a slight
      synergistic enhancement was found with a synergy index of 1.3 and 1.6,
      respectively. Even though TiO(2) sonophotocatalysis showed an additive process
      effect in the mineralization, a significant synergy effect was observed for the
      sonophotocatalysis in the presence of Fe(3+). This might be due to the formation
      of photoactive complexes between Fe(3+) and IBP degradation products, such as
      carboxylic acids. High performance liquid chromatography (HPLC) and electrospray
      ionisation mass spectrometry (ESMS) techniques were employed for the
      identification of the degradation intermediates. The sonication of IBP led to the
      formation of its mono- and di-hydroxylated intermediates. Apart from the
      hydroxylated intermediates, products formed due to the oxidation of propanoic
      acid and isobutyl substituents of IBP were also observed.

PMID- 20149535
TI  - Preparation, characterization, photocatalytic properties of titania hollow sphere
      doped with cerium.
AB  - Ce-doped titania hollow spheres were prepared using carbon spheres as template
      and Ce-doped titania nanoparticles as building blocks. The Ce-doped titania
      nanoparticles were synthesized at low temperature. The prepared hollow spheres
      were characterized by X-ray diffraction (XRD), transmission electron microscope
      (TEM), X-ray photoelectron spectroscopy (XPS) and UV-vis diffuse reflectance
      spectrum (DRS). The effect of Ce content on the physical structure and
      photocatalytic properties of doped titania hollow sphere samples was
      investigated. Results showed that there was an optimal Ce-doped content (4%) for
      the photocatalytic activity of X-3B degradation. The apparent rate constant of
      the best one was almost 31 times as that of P25 titania. The mechanism of
      photocatalytic degradation of dyes under visible light irradiation was also
      discussed.

PMID- 20149536
TI  - Commentary: a burning question of subgroup analysis in pain trials.

PMID- 20149537
TI  - A method for correcting the effect of specimen drift on coherent diffractive
      imaging.
AB  - Coherent diffractive imaging involves the inversion of a diffraction pattern to
      find the wave function at the exit-surface plane of the specimen. It is a
      promising technique for imaging, for example, nanoparticles with electrons and
      biological molecules with X-rays. If the illumination is not a plane wave of
      infinite extent, then a relative drift between the illumination and the object
      introduces errors into the diffraction pattern; an issue which is often
      overlooked. This may be of particular importance for applications with electron
      microscopes which use nanoscale probes. Here we show that beams which are uniform
      over a sufficiently large region can be used to pose a phase retrieval problem
      that is immune from specimen drift, provided suitable analysis of the diffraction
      data is undertaken. The method only applies to objects contained within a support
      that is smaller than a uniform region of the beam.

PMID- 20149538
TI  - Investigation of integrin expression on the surface of osteoblast-like cells by
      atomic force microscopy.
AB  - The transforming growth factor beta1 (TGF-beta1) is a human cytokine which has
      been demonstrated to modulate cell surface integrin repertoire. In this work
      integrin expression in response to TGF-beta1 stimulation has been investigated on
      the surface of human osteoblast-like cells. We used atomic force microscopy (AFM)
      and confocal laser scanning microscopy to assess integrin expression and to
      evaluate their distribution over the dorsal side of the plasma membrane. AFM
      probes have been covalently functionalized with monoclonal antibodies specific to
      the beta1 integrin subunit. Force curves have been collected in order to obtain
      maps of the interaction between the immobilized antibody and the respective cell
      membrane receptors. Adhesion peaks have been automatically detected by means of
      an ad hoc developed data analysis software. The specificity of the detected
      interactions has been assessed by adding free antibody in the solution and
      monitoring the dramatic decrease in the recorded interactions. In addition, the
      effect of TGF-beta1 treatment on both the fluorescence signal and the adhesion
      events has been tested. The level of expression of the beta1 integrin subunit was
      enhanced by TGF-beta1. As a further analysis, the adhesion force of the single
      living cells to the substrate was measured by laterally pushing the cell with the
      AFM tip and measuring the force necessary to displace it. The treatment with TGF
      beta1 resulted in a decrease of the cell/substrate adhesion force. Results
      obtained by AFM have been validated by confocal laser scanning microscopy thus
      demonstrating the high potential of the AFM technique for the investigation of
      cell surface receptors distribution and trafficking at the nanoscale.

PMID- 20149540
TI  - Correction of distortion due to thermal drift in scanning probe microscopy.
AB  - A common source of distortion in scanning probe microscope (SPM) images is
      "thermal drift," the slow thermal expansion of different materials in the sample
      and microscope due to small changes in temperature over the course of a scan. We
      describe here a method for correcting this distortion by immediately following
      each image scan with a rescan of a small, narrow portion of the same area with
      the slow and fast scan axes reversed. The original, full image is corrected using
      a low-order polynomial mapping function, with coefficients determined by a pixel
      wise comparison between the original full and rescanned partial images. We
      demonstrate here that this method can correctly remove distortion from a wide
      range of images with a precision of better than one pixel, and is also robust to
      common imaging artifacts. We also address some of the programming considerations
      that have gone into implementing this computationally intensive technique, which
      can now be performed using standard desktop hardware in times that range between
      a few seconds and a few minutes.

PMID- 20149539
TI  - A novel AFM based method for force measurements between individual hair strands.
AB  - Interactions between hairs and other natural fibers are of broad interest for
      both applications and fundamental understanding of biological interfaces. We
      present a novel method, that allows force measurements between individual hair
      strands. Hair fragments can be laser-cut without altering their surface
      chemistry. Subsequently, they are glued onto Atomic force microscopy (AFM)
      cantilevers. This allows carrying out measurements between the hair fragment and
      surface immobilized hair in a well-defined crossed-cylinder geometry. Both force
      distance and friction measurements are feasible. Measurements in air with
      controlled humidity and in aqueous environment show clear differences which can
      be explained by the dominating role of capillary interactions in air. Friction is
      found to be anisotropic, reflecting the fine structure of hair cuticula. While
      the investigations are focused on the particular example of human hair, we expect
      that the approach can be extended to other animal/plant fibers and thus offers
      perspectives for broad spectrum systems.

PMID- 20149541
TI  - Vertical migration of Haemonchus contortus infective larvae on Cynodon dactylon
      and Paspalum notatum pastures in response to climatic conditions.
AB  - Observations were made on vertical migration patterns of Haemonchus contortus
      infective larvae on Cynodon dactylon (bermudagrass) and Paspalum notatum
      (bahiagrass) pastures under summer climatic conditions typical of East Texas. Ten
      thousand H. contortus infective larvae (L3) were introduced to 100 cm(2) subplots
      of each pasture species within a plot area of 1m(2). Subplots were inoculated
      with larvae by applying them in an aqueous medium to the soil or mat beneath the
      vegetation. Herbage from the inoculated areas was harvested on 5 sampling days
      over a span of 21 days. L3 recoveries were observed and recorded each day on four
      herbage strata viz. 0-5, 5-10, 10-20 and >20 cm from ground level. The log
      transformed larval recovery data were analyzed for effect of day, stratum, and
      day x stratum interaction for each grass species during two separate experimental
      periods. Precipitation, relative humidity and temperature during the study were
      subjected to correlation and multiple regression analyses with the larval counts.
      Significant (P</=0.0017) differences were found for the effect of day on larval
      recoveries. No significant differences were detected for stratum or day x stratum
      interaction effects, though stratum provided a strong indication of influencing
      larval recovery. A high positive correlation (>or=0.93) between rainfall and
      total average daily larval counts was apparent. The multiple regression analysis
      did not show significant results for any of the climatic factors tested. This
      study showed that the H. contortus infective larvae can survive beyond 21 days in
      the soil and infest pasture grasses when the climatic conditions are favorable.
      Avoiding use of H. contortus contaminated pasturelands in summer at the onset of
      rainfall following a dry spell may effectively reduce nematode loads in
      susceptible farm animals. Additional studies should focus on factors affecting
      long term L3 survivability, migrational pattern on these and other plant species
      and the relationship between climatic factors and larval migration patterns
      throughout the year. Total larval recovery of H. contortus in this study was
      greater in bahiagrass than bermudagrass. While the design of this study did not
      allow for testing one pasture species against another, studies with potted plants
      would allow for some valid comparisons. Soil characteristics may also play a role
      in L3 survival and subsequent migration.

PMID- 20149542
TI  - Evaluation of oral tilmicosin efficacy against severe cryptosporidiosis in
      neonatal kids under field conditions.
AB  - Many compounds have been screened for their potential anti-cryptosporidial
      activity in ruminants but none of them has been totally efficient in controlling
      the disease. Macrolide antibiotics have demonstrated some activity against
      Cryptosporidium spp. in humans. Tilmicosin is a macrolide antibiotic, available
      in France in an oral form (Pulmotil AC, Lilly France). The preventive efficacy of
      tilmicosin was evaluated in a goat farm experiencing severe clinical
      cryptosporidiosis in kids. Twenty-two kids were separated from their dams just
      after birth and placed in a separated pen. They were divided into 3 groups: an
      untreated group (10 kids), group 1 (6 kids) receiving tilmicosin at 25mg/kg
      BW/day and group 2 (6 kids) receiving tilmicosin at 50mg/kg BW/day. Tilmicosin
      was individually given by oral route from day 2 of age for 10 days. Three times a
      week, individual faecal samples were performed to assess the oocyst output.
      Clinical data, i.e. diarrhea and mortality, were recorded. In control kids, the
      highest prevalence and intensity of excretion were observed between day 6 and day
      16 of age and mortality reached 90%. Excretion dynamic and clinical consequences
      were similar in both treated kid groups. Finally, tilmicosin did not demonstrate
      any activity against severe kid cryptosporidiosis in field conditions.

PMID- 20149543
TI  - FLOTAC: an improved method for diagnosis of lungworm infections in sheep.
AB  - The FLOTAC techniques involve the spinning of faecal samples onto the surface of
      counting chambers to permit enumeration of parasitic elements (eggs, larvae,
      oocysts and cysts) to an accuracy of one parasitic element per gram of faeces. In
      the present study it is demonstrated that FLOTAC provides a rapid and very
      sensitive method for counting of lungworm larvae of sheep. The optimum flotation
      solution for lungworm larvae is zinc sulphate and mercury II iodide (s.g. 1.45)
      although zinc sulphate (s.g. 1.20 or 1.35) on its own also gave good results.
      Samples preserved in 5% formalin gave the highest counts but fresh, frozen and
      samples in 10% formalin also gave higher counts than McMaster and simple
      flotation. Larval counts of 307 field samples gave up to 1.27x more positives
      samples than use of Baermann funnels and up to 4.18x more larvae per sample. As
      FLOTAC is faster than Baermannisation of samples it offers a better method of
      counting larvae in ruminant faecal samples.

PMID- 20149544
TI  - In vitro activity and preliminary toxicity of various diamidine compounds against
      Trypanosoma evansi.
AB  - Trypanosoma evansi is an animal pathogenic protozoan, causing a wasting disease
      called Surra, which is broadly distributed in a wide range of mammalian hosts.
      Chemotherapy is the most efficient control method, which depends on four drugs.
      Unfortunately, with the appearance of resistance to these drugs, their effective
      use is threatened, emphasising a need to find new drugs. Diamidines bind to the
      minor groove of DNA at AT-rich sites and exert their anti-trypanosomal activity
      by inhibiting one or more DNA dependent enzymes or by directly impeding the
      transcription process. In total, 67 novel diamidine compounds were tested in
      vitro to determine activity against an animal pathogenic Chinese kinetoplastic T.
      evansi strain. In comparison, a human pathogenic Trypanosoma brucei rhodesiense
      strain and a P2 transporter knock out of a Trypanosoma brucei brucei strain were
      also tested. All diamidine compounds tested in this study against T. evansi
      produced inhibitory concentration (IC(50)) values below 50 nM. The results
      demonstrate that these compounds are highly active against T. evansi in vitro. In
      addition, preliminary in vivo toxicity tests were performed on all 67 diamidines
      with 69% of the compounds showing no acute toxicity at an intra-peritoneal dose
      of 100mg/kg.

PMID- 20149545
TI  - Seroprevalence of canine leishmaniasis and environmental change.

PMID- 20149546
TI  - First description of Cryptosporidium bovis in Japan and diagnosis and genotyping
      of Cryptosporidium spp. in diarrheic pre-weaned calves in Hokkaido.
AB  - Eighty fecal samples from pre-weaned calves with diarrhea were collected in the
      Tokachi area in Northern Japan to investigate the prevalence of Cryptosporidium
      species in such animals. Oocysts from fecal samples collected from each animal
      were concentrated using sucrose gradient centrifugation. Genomic DNA was
      extracted from each sample and processed by nested PCR to amplify the partial SSU
      rRNA gene of Cryptosporidium. Cryptosporidium infections were detected in 75% of
      the samples. Sequence analysis was performed on all positive samples.
      Phylogenetic analysis of 33 successfully sequenced isolates of the SSUrRNA PCR
      products revealed all but one were Cryptosporidium parvum infections. The
      remaining single case was Cryptosporidium bovis. These findings suggest that C.
      parvum is prevalent in diarrheic pre-weaned calves and can be a source of
      cryptosporidial infections for humans and animals in Hokkaido.

PMID- 20149547
TI  - The use of a simplified faecal egg count reduction test for assessing
      anthelmintic efficacy on Belgian and German cattle farms.
AB  - Anthelmintic resistant cattle nematodes have been reported in different regions
      around the world. However, in Western Europe the assessment of the problem relies
      largely on case reports and no prevalence data based on wide-scale surveys are
      available. Therefore, we performed a survey to (1) screen for reduced
      anthelmintic efficacy in Belgian and German cattle farms; (2) evaluate the
      usefulness of a simplified faecal egg count reduction test (FECRT), where
      efficacies are based on the mean FECs of 10 at random collected faecal samples
      pre- and post-treatment per farm and (3) identify possible risk factors for
      reduced anthelmintic efficacy. Of 88 farms included in this study, 84 farms used
      macrocyclic lactones (MLs). A FECR <95% was observed on 39% of these 84 farms.
      However, using a Markov chain Monte Carlo simulation analysis, to correct for the
      used McMaster FEC technique with a detection limit of 50 epg, reduced efficacy
      could only be confirmed in 25% of the farms (21/84). Only Cooperia spp. were
      found in significant numbers in the coprocultures post-treatment. Reduced
      efficacy was significantly associated with farm type and with a lower efficacy in
      beef herds compared to dairy herds. Four farms were revisited and a standardized
      FECRT was performed to confirm anthelmintic resistance (AR). Surprisingly,
      macrocyclic lactone resistance against Cooperia oncophora was only confirmed in
      one of four farms. In conclusion, our results show that a reduced efficacy
      observed in a FECRT are not only caused by AR but that the detection limit of the
      FEC technique used and the (in)correct administration of the anthelmintic drugs
      are confounding factors of major importance.

PMID- 20149548
TI  - Poultry as reservoir hosts for fishborne zoonotic trematodes in Vietnamese fish
      farms.
AB  - Fishborne zoonotic trematodes (FZT) are widespread in Vietnam and Southeast Asia.
      It is now recognized that the risk of being infected from eating raw fish dishes
      applies not only to humans, but also to domestic animals (e.g., cats, dogs, and
      pigs) and fish-eating birds. The role of ducks and chicken, commonly raised on
      fish farms, as reservoir hosts, however, has not been adequately investigated. To
      study this question, chickens and ducks from integrated poultry-fish farms in
      Nghia Lac and Nghia Phu communes, Nam Dinh province, Vietnam were surveyed for
      FZT infections. A total of 50 ducks and 50 chickens from each commune were
      examined. Results revealed that 12% of chickens and 30% of ducks were infected
      with various species of trematodes, including two zoonotic species, Centrocestus
      formosanus and Echinostoma cinetorchis. Both occurred in chickens whereas only E.
      cinetorchis was found in ducks. Prevalence of these zoonotic species was 12% and
      7% in ducks and chickens, respectively. Among other trematodes, Hypoderaeum
      conoideum, also a zoonotic fluke, was the most prevalent (20-30%). The feeding of
      snails and fish remains to poultry, either intentionally or by discharge of waste
      from the slaughter of ducks and chickens into the ponds, was identified as risk
      factors for trematode infection. The FZT species and low prevalence found in
      poultry in these communes indicate their role as reservoir hosts is minor.

PMID- 20149549
TI  - Mifepristone decreases depression-like behavior and modulates neuroendocrine and
      central hypothalamic-pituitary-adrenocortical axis responsiveness to stress.
AB  - Glucocorticoid dyshomeostasis is observed in a proportion of depressed
      individuals. As a result, glucocorticoid receptor (GR) antagonists are currently
      being tested as potential anti-depressants. The current study was designed to
      test the efficacy of mifepristone, a GR antagonist, in mitigating behavioral,
      neuroendocrine and central nervous system (CNS) responses to an acute stressor.
      Adult male rats were treated for 5 days with mifepristone (10 mg/kg) and then
      exposed to the forced swim test (FST). Treatment with mifepristone decreased
      immobility and increased swimming (but not climbing) behavior in the FST,
      consistent with anti-depressant action. In addition, mifepristone dampened the
      ACTH response to FST exposure. In the CNS, mifepristone increased c-Fos
      expression in all subdivisions of the medial prefrontal cortex (mPFC) and
      decreased neuronal activity in some subdivisions of the hippocampus including the
      CA2, CA3, and hilus region of the dentate gyrus in animals exposed to FST. In
      contrast, mifepristone increased neuronal activity in the ventral subiculum
      (output region of the hippocampus) and decreased c-Fos expression in the central
      amygdala (CeA) in animals exposed to FST. These data suggest that anti-depressant
      efficacy and perhaps HPA dampening properties of RU486 are related to alterations
      in key limbic circuits mediating CNS stress responses, resulting in enhanced
      stress inhibition (via the mPFC and ventral subiculum) as well as decreased
      stress excitation (central amygdala). Overall the data suggest that drugs
      targeting the glucocorticoid receptor may ameliorate stress dysfunction
      associated with depressive illness.

PMID- 20149550
TI  - Diabetes mellitus: hypoxia of the islets of Langerhans resulting from the
      systematic rest prone on the back after a meal?
AB  - This article presents a novel view on the diabetes aetiology from the standpoint
      of a single epidemiological factor. It has been observed that, irrespective of
      the type of diabetes, sufferers have a stable, persistent behavioural habit: to
      take a rest or to have a nap within two hours of a meal. Such habitual behaviour
      is termed as postprandial hypokinesia (PPH). The working hypothesis is that,
      after food intake and with the body in a recumbent/semirecumbent position on the
      back, the stomach replete with food places mechanical pressure against the
      pancreas. As a consequence, systematic disturbances in the microcirculatory flow
      of the islets of Langerhans (ischemia) cause hypoxia to develop which,
      ultimately, sets in train a pathological process (and later, an autoimmune
      reaction). The intensity and effect of structurally-functional disturbances are
      determined by the degree of hypoxia. Literature sources support the islets of
      Langerhans being physiologically susceptible to hypoxia. Moreover, the same
      effects of experimental hypoxia on the islets of Langerhans are also observed in
      the pathogenesis of diabetes. Accumulated scientific research makes possible to
      construct an ischemic/hypoxic model of diabetes development. The core
      pathological process then should involve all the following pathologies:
      inflammation of the islets of Langerhans, dysfunction of an insulin islet
      apparatus, apoptosis/necrosis of the cells in the insulin islets. All three are
      also observed in diabetes. From this perspective, conventional types of diabetes
      can be regarded as different states, apparently progressing, of a single
      pathological process attributed to the level reached in the compensatory capacity
      exhaustion. It follows that, with the elimination of PPH, conditions for the
      pathological process to be reversed are created: the reparation of injured
      tissues and the recovery of function to synthesise and secrete insulin are
      likely. Those patients under observation, who eliminated the PPH behaviour from
      their lifestyle, encountered a positive dynamic in terms of an increased capacity
      for work, improvement in general condition, normalization of glycemia level, a
      decrease in medication as well as remission. The major implication of the
      hypothesis, if correct and accepted, is that the use of medication on a stand
      alone basis without alterations to a lifestyle would not be sufficient to produce
      successful treatment and cure of diabetes. Behavioural therapy should be used as
      a primary causal therapeutic action. Education on the consequences of the PPH
      factor should be used as a primary preventive measure.

PMID- 20149551
TI  - Olfactory bulb dysgenesis, mirror neuron system dysfunction, and autonomic
      dysregulation as the neural basis for autism.
AB  - Autism is a disorder characterized by social withdrawal, impoverished language
      and empathy, and a profound inability to adopt another's viewpoint - a failure to
      construct a "theory of mind" for interpreting another person's thoughts and
      intentions. We previously showed that these symptoms might be explained, in part,
      by a paucity of mirror neurons. Prompted by an MRI report of an individual with
      autism, we now suggest that there may be, in addition, a congenital
      aplasia/dysplasia of the olfactory bulbs with consequent reduction of vasopressin
      and oxytocin receptor binding. There may also be sub-clinical temporal lobe
      epilepsy affecting the recently discovered third visual system that is rich in
      "empathy" related mirror neurons (MNS) and projects (via the TOP junction - just
      below the inferior parietal lobule) to limbic structures that regulate autonomic
      outflow. This causes deranged autonomic feedback, resulting in additional
      deficiencies in MNS with loss of emotional empathy and introspection.

PMID- 20149552
TI  - Potential teratogenic effects of ultrasound on corticogenesis: implications for
      autism.
AB  - The phenotypic expression of autism, according to the Triple Hit Hypothesis, is
      determined by three factors: a developmental time window of vulnerability,
      genetic susceptibility, and environmental stressors. In utero exposure to
      thalidomide, valproic acid, and maternal infections are examples of some of the
      teratogenic agents which increase the risk of developing autism and define a time
      window of vulnerability. An additional stressor to genetically susceptible
      individuals during this time window of vulnerability may be prenatal ultrasound.
      Ultrasound enhances the genesis and differentiation of progenitor cells by
      activating the nitric oxide (NO) pathway and related neurotrophins. The effects
      of this pathway activation, however, are determined by the stage of development
      of the target cells, local concentrations of NO, and the position of nuclei
      (basal versus apical), causing consequent proliferation at some stages while
      driving differentiation and migration at others. Ill-timed activation or
      overactivation of this pathway by ultrasound may extend proliferation, increasing
      total cell number, and/or may trigger precipitous migration, causing
      maldistribution of neurons amongst cortical lamina, ganglia, white matter, and
      germinal zones. The rising rates of autism coincident with the increased use of
      ultrasound in obstetrics and its teratogenic/toxic effects on the CNS demand
      further research regarding a putative correlation.

PMID- 20149553
TI  - Can the existence of highly accessible concrete representations explain savant
      skills? Some insights from synaesthesia.
AB  - The present review argues that the reification of abstract concepts provides a
      psychological mediating mechanism for calendar and lightning calculation and
      possibly even all savant skills. The argument, which draws heavily on the
      synaesthesia literature has two main strands. First, there is anecdotal evidence
      for the presence and utilisation of highly accessible concrete representations of
      abstract concepts in savants. Second, synaesthetes who possess these structures
      experience cognitive benefits in the same domain. The present review concludes
      that the putative mechanism discussed here is plausible and has some empirical
      support, however, is in need of further testing. A number of ways in which to
      proceed in this task are suggested.

PMID- 20149554
TI  - Potential atrial arrhythmogenicity of adipocytes: implications for the genesis of
      atrial fibrillation.
AB  - Atrial fibrillation is the most common sustained cardiac arrhythmia. Obesity and
      metabolic syndrome are independent risk factors for atrial fibrillation, and
      epicardial adipose tissues are highly associated with the genesis of atrial
      fibrillation, compared to visceral fat. Adipocytes can produce inflammatory
      cytokines and adipocytokines, which may enhance inflammation and oxidative stress
      in patients with obesity or metabolic syndrome. Moreover, it is possible that
      local interactions between epicardial adipose tissue and the adjacent myocardium
      can directly produce electrical or structural remodelings in the atrium. Taken
      together, we hypothesized that epicardial adipocytes contain distinctive
      arrhythmogenicity through increases in inflammatory cytokines, adipocytokines,
      and adipocyte-cardiomyocyte interactions to induce atrial fibrillation.

PMID- 20149555
TI  - Could stroma contribute to field cancerization?
AB  - The common oral diseases as well as oral cancer have the characteristic of field
      cancerization or field effect. Field cancerization, characterized by phenotypic
      and genetic changes in the neighboring cells of the frank cancer cells, is a
      clinical phenomenon first found in head and neck cancers. Field cancerization of
      the epithelia is currently a widely-accepted model in cancer biology as a
      manifestation of cancer progression. The concomitant changes in the tumor
      microenvironment have drawn more attention recently. Could the changes in the
      tumor microenvironment and the epithelial field cancerization concepts be linked?
      In view of the importance of stroma in the development of epithelium and evidence
      in carcinoma-associated stroma, we propose the question if stroma not only
      reciprocates the neoplastic changes of the epithelia, but also contributes to
      field cancerization. Actually one perspective paper pointed out that healing
      wound can influence the recurrence of field cancerization. In another words, the
      microenvironment of healing wound determines the prognosis of field
      cancerization. Based on the literatures published and our own work, we
      hypothesize a new model of field cancerization focusing on the co-evolution of
      the tumor microenvironment. We suggest that the microenvironment cannot be
      neglected when treating diseases with characteristics of field cancerization.

PMID- 20149556
TI  - Comment on "calcium channel as a potential anticancer agent".

PMID- 20149557
TI  - Molecular characterization of methicillin-resistant Staphylococcus aureus
      isolates in Algeria.
AB  - INTRODUCTION: The epidemiology of Staphylococcus aureus has changed radically
      since 1999, in particular, methicillin-resistant S. aureus (MRSA), originally
      restricted to hospital, has emerged as a significant pathogen in the community,
      and true community-acquired MRSA (CA-MRSA) infections have been reported in
      patients with no clear risk factors. CA-MRSA strains frequently produce Panton
      Valentine leukocidin (PVL). OBJECTIVES: The objectives of this study were: (i) to
      monitor the prevalence of PVL and toxic shock syndrome toxin-1 (TSST-1) isolates
      MRSA; (ii) to identify the staphylococcal cassette chromosome (SCCmec) types of
      MRSA isolates. MATERIAL AND METHODS: Sixty-four isolates, collected between 2005
      and 2007 in Didouche Mourad hospital of Algeria. The isolates were identified by
      conventional methods. The antibiotic susceptibility of the isolates was performed
      using the disk diffusion method and automat Vitek2. The presence of gene mecA,
      the genes encoding SCCmec type, PVL and TSST-1 toxins were investigated by real
      time PCR. RESULTS: All strains were gene mecA positives, 32 (50%) harboured
      SCCmec IV type, 28 (43.75%) harboured SCCmec V type. 19 (29.68%) have been
      identified positive for the leukocidin toxin (PVL), they harboured SCCmec type
      IV. The virulence factor TSST-1 was not present among these isolates. CONCLUSION:
      These results show a high prevalence of PVL-positive H-MRSA in our wards.

PMID- 20149558
TI  - Validation of a measure to assess alcohol- and marijuana-related risks and
      consequences among incarcerated adolescents.
AB  - Few measures exist to assess risky behaviors and consequences as they relate to
      substance use in juvenile delinquents. This study sought to validate such a
      measure on a racially and ethnically diverse sample (N=175). Results indicate
      that alcohol-related risky behaviors and consequences comprise a single scale as
      do marijuana-related risky behaviors and consequences. Furthermore, results
      suggest that the retention of common items for both scales produces reliable and
      valid scales and maintains parsimony. Internal consistencies were more than
      adequate (0.72-0.83) and test-retest stabilities, even across several months were
      acceptable (0.52-0.50). The scales evidenced a high degree of concurrent and
      predictive incremental validity in predicting conduct disorder, dependence
      symptoms, and consumption patterns. Researchers can use these scales to measure a
      generalized construct tapping risks and consequences as related to alcohol and
      marijuana use. Ease of use may make these scales appealing to clinicians who can
      provide feedback to clients regarding risky behaviors involving alcohol and
      marijuana.

PMID- 20149559
TI  - Subjective effects to marijuana associated with marijuana use in community and
      clinical subjects.
AB  - INTRODUCTION: Marijuana is the most commonly used illicit drug among adolescents.
      Marijuana use induces both psychological and physiological responses, which can
      be interpreted by an individual in a variety of ways (i.e. subjective effects).
      We have examined subjective effects in adolescent, young adult community, and
      clinical populations to determine how patterns of use may be predicted by an
      individual's subjective experiences with the drug. METHOD: Participants were
      community and clinical sample subjects drawn from the Colorado Center of
      Antisocial Drug Dependence (CADD) and a sample of adjudicated youth from the
      Denver metropolitan area (aged 11-30). They were evaluated with the Composite
      International Diagnostic Interview-Substance Abuse Module (CIDI-SAM) and the
      Lyons battery for subjective effects. Scales for subjective effects were created
      using Mokken scale analysis. Multivariate linear and logistic regression was used
      to examine associations between the subjective scales and marijuana outcomes.
      RESULTS: Mokken scaling revealed two subjective effects scales, positive and
      negative. Both scales were significantly positively associated with marijuana
      abuse or dependence in both the community and clinical sample and regular use in
      the community sample. The negative scale was negatively associated with past six
      month use in the community sample (p<0.05) and clinical sample, after controlling
      for age and gender effects. CONCLUSIONS: These findings suggest that diverse
      subjective experiences with marijuana can be ordered hierarchically and that the
      resulting short scales can be used in either clinical or community settings.
      Further, they suggest that the potential for marijuana use problems is related to
      the type of subjective experience from marijuana exposure.

PMID- 20149561
TI  - Real-time PCR culture and serology for the diagnosis of Mycoplasma gallisepticum
      in chicken breeder flocks.
AB  - This study aimed to compare a real-time PCR (rPCR) test with improved detection
      limit to serology and culture for the detection of Mycoplasma gallisepticum (MG)
      infection in chicken breeder flocks. Six hundred and forty-six blood and tracheal
      swab samples belonging to 31 grandparent chicken breeder flocks were tested by
      rPCR. The detection limit of rPCR was 0.9 pg microl(-1), with pure MG S6 strain
      DNA and 100 colony forming units (CFUs) ml(-1), where both pure culture and
      tracheal swabs were artificially spiked with the same strain. The seropositive
      flock rate based on both MG RPA and HI were calculated as 48.4% (15/31) and 32.3%
      (10/31), respectively, while culture- and rPCR-positive flock rates were 16.1%
      (5/31) and 29.0% (9/31), respectively. On flock-based analysis, culture method
      detected 5 out of 10 MG seropositive flocks (sensitivity 50%, specificity 100%),
      whereas rPCR detected 8 out of 10 flocks (sensitivity 80%, specificity 95%).
      Agreements between serology and culture, and serology and rPCR were 83.9% and
      90.3%, respectively. On individual sample-based analysis, culture method detected
      26 out of 78 MG seropositive chicken (sensitivity 33%, specificity 100%), whereas
      rPCR detected 51 out of 78 MG seropositive chickens (sensitivity 65%, specificity
      96%). There was 91.9% and 91.4% agreement between serology and culture, and
      serology and rPCR, respectively. Results of this study indicate that the rPCR
      with improved in vitro detection limit could detect MG in seropositive chicken
      flocks. Therefore, we advise the use of rPCR and/or culture for confirmation of
      serology results obtained from screening MG infection in chicken flocks.

PMID- 20149562
TI  - Heart rate variability in infants with central coordination disturbance.
AB  - Despite a remarkable medical progress in the field of Developmental Medicine and
      Child Neurology, early identification of infants at risk for permanent motor
      disabilities still presents challenge for both clinicians and researchers. As an
      indicator of cardiac autonomic control, it was shown that heart rate variability
      (HRV) might reflect not only sympathetic or parasympathetic activity but also
      functional integrity of the central nervous system (CNS). Furthermore a pattern
      of HRV was demonstrated to correlate with motor developmental outcome in high
      risk infants. The purpose of this study was to analyze the clinical usefulness as
      well as predictive value of time-domain HRV parameters in infants with central
      coordination disturbance. The study included 35 infants with central coordination
      disturbance and 37 healthy age and sex-matched controls. Time-domain HRV indices
      were analyzed from 24-h electrocardiography recordings. We found significantly
      lower values of SDNN, SDANN and RMSSD parameters in infants with central
      coordination disturbance compared to controls. Additionally, logistic regression
      analyses demonstrated independent predictive value of parameters SDNN and SDANN
      in infants who subsequently developed cerebral palsy (CP). By performing receiver
      operating characteristic (ROC) analyses, the optimal cut-off value of SDNN<=48ms
      predicted CP with a sensitivity of 68.7% (95% CI 41.4-88.9) and specificity of
      84.2% (95 CI 60.4-96.4) while the optimal cut-off value of SDANN<=41ms predicted
      CP with a sensitivity of 87.5% (95% CI 61.6-98.1) and specificity of 57.9% (95 CI
      33.5-79.7). We are in opinion that time domain HRV analysis could be helpful
      clinically as well as a prognostic tool in infants with central coordination
      disturbance.

PMID- 20149563
TI  - Dynamics of sperm DNA fragmentation in the swine: ejaculate and temperature
      effects.
AB  - The dynamics of sperm DNA fragmentation was examined in 16 boar ejaculates using
      the sperm chromatin dispersion (SCD) test and a two-tail comet assay. The net
      sperm rich fraction was preserved at two different temperatures (Trial 1: 15
      degrees C, n=10; Trial 2: 37 degrees C, n=6) and sub-samples were taken every day
      until a sperm motility of zero. Significant differences in the dynamics of DNA
      fragmentation were observed among the different ejaculates and also according to
      the storage temperature. After analyzing the dynamic response of the sperm DNA
      damage, when the sperm samples are incubated at 15 or 37 degrees C, each
      ejaculate could be classified and a considerable variation among individuals for
      an increase in DNA damage was observed. Thus, while in some ejaculates no rise in
      DNA fragmentation was observed, in others, the sperm DNA fragmentation process
      was triggered during the initial days of the experiment. In general, sperm
      incubation at 37 degrees C diminished sperm DNA quality. The two-tail comet assay
      indicated that at time zero existing DNA damage mainly consisted of double
      stranded DNA breakage. During storage, DNA damage affected one of the DNA strands
      until a second wave of DNA damage, in which there was both single and double
      stranded DNA damage.

PMID- 20149564
TI  - The management of gastric perforation in a girl with Rett syndrome: report of a
      case.
AB  - INTRODUCTION: Rett syndrome is a neurologically disorder that affects
      approximately one in 10,000 females. CASE REPORT: A 21-year-old girl with Rett
      syndrome was hospitalized for abdominal distention and pain. Physical examination
      revealed abdominal tenderness. Radiology investigation revealed bilateral free
      air in subdiaphragmatic area. Gastric perforation observed at laparotomy. Primary
      suturing and omentoplasty were performed. In the follow-up, the symptoms of
      intestinal obstruction occurred. Conservative treatment failed and second
      intervention was performed. At laparotomy severe gastric and intestinal
      dilatation and bowel adhesions were detected. Adhesiolysis, tube gastrostomy, and
      feeding jejunostomy performed. DISCUSSION: Rett syndrome and associated gastric
      complications are uncommon. These pathologic disorders may cause gastric,
      intestinal necrosis, intestinal obstructions. Because of the late occurring of
      physical findings and insidious presentation of the gastrointestinal perforations
      in Rett syndrome, physicians should keep in mind this rare entity to reduce
      morbidity and mortality.

PMID- 20149565
TI  - Image quality of T2w-TSE of the abdomen and pelvis with Cartesian or BLADE-type k
      space sampling: a retrospective interindividual comparison study.
AB  - PURPOSE: The purpose of this study was to evaluate the image quality of T2
      weighted (T2w) imaging of the abdomen and pelvis based on the acquisition of
      rotating rectangular stripes of k-space data after successive radiofrequency
      excitation (BLADE technique) in comparison to T2w turbo-spin-echo (TSE) sequences
      with Cartesian k-space sampling. MATERIALS AND METHODS: A total number of 107
      patients with MR imaging of the abdomen or the pelvis were included in this
      retrospective interindividual study. All exams were performed in the clinical
      routine at 1.5T. The T2w images were randomly performed in BLADE technique or as
      TSE sequences. Two blinded radiologists assessed the images, presented in a
      random order, concerning the delineation of the abdominal and the musculoskeletal
      structures, the artifacts of these structures, and the overall image qualities.
      RESULTS: For the abdomen the mean overall image quality of the T2w-BLADE was
      rated 3.2 vs. 3.1 for T2w-TSE (p=0.871). The mean musculoskeletal/visceral
      artifacts of the T2w-BLADE were scored as 2.9/3.0 vs. 3.2/2.6 for the T2w-TSE
      (p=0.101/p=0.051). The delineation of the musculoskeletal, respectively of the
      visceral structures was assessed for the T2w-BLADE as 3.0/3.4 vs. 3.2/3.1 for the
      T2w-TSE (p=0.263; p=0.185). For the pelvis the mean overall image quality of the
      T2w-BLADE was 3.4 vs. 2.9 for the T2w-TSE (p=0.005). Furthermore the
      musculoskeletal/visceral artifacts were assessed with a mean of 3.6/3.3 for the
      T2w-BLADE vs. 3.0/2.8 for the T2w-TSE (p=0.005; p=0.011). The
      musculoskeletal/visceral delineation of the T2w-BLADE was rated 3.6/3.4 vs.
      3.0/2.8 for the T2w-TSE sequence (p<0.001; p=0.008). CONCLUSION: In imaging of
      the pelvis the overall quality of T2w sequences with k-space sampling in BLADE
      technique was rated significantly superior compared with the standard Cartesian
      sampling. Similar results were assessed for the reduction of the amount of
      artifacts and blurring. By contrast, no significant benefit could be demonstrated
      for the T2w-BLADE in the abdomen.

PMID- 20149566
TI  - Quantitative determination of hippuric and benzoic acids in urine by LC-MS/MS
      using surrogate standards.
AB  - An LC-MS/MS method for simultaneous determination of hippuric acid (HA) and
      benzoic acid (BA) in monkey urine after direct injection was developed. Since HA
      and BA are endogenous compounds in urine, surrogate standards ((13)C(6)-hippuric
      and (13)C(6)-benzoic acid) were employed to generate calibration curves. l
      Phenylalanine-ring-D5 served as an internal standard. Multiple reaction
      monitoring in the negative ionization mode with an APCI source was used for
      detection of all components in the assay. The developed method is intended for
      determination of HA and BA in the range of 0.25-250 and 0.1-100microg/ml,
      respectively. Weighted (1/x) quadratic regression (r(2)>0.99) was used to
      generate calibration curves. Precision and accuracy of the method were assessed
      by analyzing 3 quality control samples (concentrations at low, medium, and high
      range of calibration curve) prepared in monkey urine. Stability for 48h at room
      temperature and after 3 freeze-thaw cycles was also evaluated. The proposed
      method was successfully utilized for analysis of urine samples from female
      monkeys following the administration of everninomicin alone and in combination
      with gentamicin. The concentrations of endogenous HA and BA were calculated based
      on the peak area ratio of the analyte to the internal standard using a regression
      equation for corresponding surrogate standard.

PMID- 20149567
TI  - A novel method for quantitative measurement of a therapeutic monoclonal antibody
      in the presence of its target protein using enzymatic digestion.
AB  - Over the past decades, the use of therapeutic monoclonal antibodies (mAbs) has
      become an important strategy in the treatment of various diseases. To enable
      pharmacokinetic (PK) assessment, specific immunoassays need to be developed to
      quantify mAbs in blood. In these assays, the presence of bound target protein can
      lead to severe underestimation of mAb concentration. Here we describe a novel
      approach for the quantification of total (free plus bound) human mAb
      concentration, in human and non-human primate serum, in the presence of a high
      level of target protein. The method is based on sample digestion with pepsin
      under optimized conditions to fully digest the target while keeping the mAb in
      the form of immunoreactive fragments. The quantification of mAb is then performed
      by ELISA without interference from the target. This method allows accurate
      quantification of as low as 50ng/ml mAb in the presence of up to 100-fold target
      molar excess. Intra- and inter-run precision is better than 10%, and intra- and
      inter-run accuracy in the range of 89.3-106.7%. In conclusion, this general and
      simple approach allows the accurate and sensitive measurement of preclinical and
      clinical samples avoiding target interference.

PMID- 20149568
TI  - Simultaneous HPLC determination of tolbutamide, phenacetin and their metabolites
      as markers of cytochromes 1A2 and 2C6/11 in rat liver perfusate.
AB  - A new, simple, rapid, sensitive, and repeatable reversed-phase HPLC method was
      developed and validated for the simultaneous determination of tolbutamide,
      phenacetin and their metabolites in rat liver perfusate. Chlorpropamide was used
      as an internal standard to ensure the precision and accuracy of this method.
      Analytes were extracted into diethyl ether using a two-step liquid-liquid
      extraction. A C18 analytical column and a mobile phase composed of acetonitrile
      and potassium phosphate buffer were used for the chromatographic separation with
      UV detection. Limits of detection varied between 20 and 46ng/mL for phenacetin,
      tolbutamide and their metabolites. The overall extraction recovery for the
      analytes varied from 65.4% in paracetamol to 88.0% in tolbutamide for
      concentrations within the expected range of concentrations from previous
      experimental samples. In terms of precision, the intra- and inter-day variation
      at three different concentrations in all analytes never exceeded 7.6 and 11.4%,
      respectively. This method is applicable for the modeling and description of
      possible pharmacological interactions on rat cytochromes P450 1A2 and 2C6/11 or
      can be used for in vitro evaluation of both cytochromes 1A2 and 2C.

PMID- 20149569
TI  - Rapid quantification of phenolic acids in radix Salvia miltiorrhiza extract
      solutions by FT-NIR spectroscopy in transflective mode.
AB  - A rapid method for simultaneous determination of main phenolic acids in Radix
      Salvia Miltrorrhiza extract solutions was developed using Fourier transform near
      infrared spectroscopy in transflective mode and multivariate calibration and HPLC
      UV as the reference method. Partial least squares (PLS) algorithm was conducted
      on the calibration of regression models. The multiplicative scatter correction,
      Norris derivative and second derivative were adopted for the spectral pre
      processing, and the number of PLS factors were optimized by leave-one-out cross
      validation. The performance of the final model was evaluated according to root
      mean square error of prediction (RMSEP) and correlation coefficient (R). The R
      values achieved in the prediction set were above 0.93. The developed models were
      used for analysis of unknown samples and routine monitoring with satisfactory
      results. This work demonstrated that NIR spectroscopy combined with PLS algorithm
      could be used for the rapid determination of the main phenolic acids of Salvia
      Miltrorrhiza extract solutions.

PMID- 20149570
TI  - Past-year intentional and unintentional injury among teens treated in an inner
      city emergency department.
AB  - An inner-city emergency department (ED) visit provides an opportunity for contact
      with high-risk adolescents to promote injury prevention. OBJECTIVES: To identify
      the prevalence of injuries sustained over the past year by teens presenting to an
      inner-city ED, and to identify factors associated with recent injury to inform
      future ED-based injury prevention initiatives. METHODS: Over 1 year, 7 days a
      week, from 1:00-11:00 p.m., patients aged 14-18 years presenting to the ED
      participated in a survey regarding past-year risk behaviors and injuries.
      RESULTS: Of the entire group of teens presenting to the ED (n = 1128) who
      completed the survey (83.8% response rate), 46% were male, and 58% were African
      American. Past-year injuries were reported by 768 (68.1%) of the teens; 475
      (61.8%) of those reported an unintentional injury and 293 (38.1%) reported an
      intentional injury. One-third of all youth seeking care reported a past-year
      sports-related injury (34.5%) or an injury related to driving or riding in a car
      (12.3%), and 8.2% reported a gun-related injury. Logistic regression found that
      binge drinking (adjusted odds ratio [AOR] 1.95) and illicit weapon carrying (AOR
      2.31) predicted a past-year intentional injury. African-American youth (AOR 0.56)
      and those receiving public assistance (AOR 0.73) were less likely to report past
      year unintentional injuries. CONCLUSIONS: Adolescents seeking care in an inner
      city ED, regardless of the reason for seeking care, report an elevated prevalence
      of recent injury, including violence. Future injury screening and prevention
      efforts should consider universal screening of all youth seeking ED care.

PMID- 20149571
TI  - The route to change: within-session predictors of change plan completion in a
      motivational interview.
AB  - This study is the first to examine within-session therapist and client
      language/process predictors of a client's decision to complete a written Change
      Plan in an alcohol-focused motivational interview (MI). Data were from an ongoing
      hospital-based clinical trial (N = 291). Trained raters coded audiorecorded MI
      sessions using the Motivational Interviewing Skill Code. Logistic regression
      analyses found that therapist MI-consistent behaviors (b = .023, p < .001) and
      client change talk (b = .063, p < .001) were positive predictors, and client
      counter change talk (b = -.093, p < .001) was a negative predictor of the
      decision to complete a Change Plan regarding alcohol use. Mean comparisons showed
      that compared to noncompletion, Change Plan completion did not result in
      significantly greater changes in client motivational readiness. Completion of a
      Change Plan is a proximal outcome in MI that is associated with client intention
      to change (change talk) and may predict follow-up alcohol outcomes. Analyses of
      such theory-driven proximal client mechanisms provide a more complete model of MI
      process and may inform MI providers of necessary treatment ingredients.

PMID- 20149572
TI  - B-type natriuretic peptide protects cardiomyocytes at reperfusion via
      mitochondrial calcium uniporter.
AB  - B-type natriuretic peptide (BNP) is a regulatory autacoid in the mammalian
      myocardium, whose functions play significant roles in health and disease.
      Previous work has identified that BNP protect myocardium through mitochondrial
      pathway-dependent mechanism against ischemia-reperfusion (I/R) injury.
      Mitochondria are both essential effectors of cardioprotection and primary targets
      of cardioprotective signaling. In particular, mitochondrial channel are activated
      to act as the major determinants of cell life and death. Since the discovery of
      mitochondrial calcium uniporter (MCU), MCU has been its contribution to
      cardiomyocytes under specific physiological or pathological conditions. The role
      of mitochondria and MCU, in mediating reperfusion-induced heart injury is a novel
      investigative area. In addition, the relationship of BNP with MCU in
      cardiomyocytes undergoing reperfuison is unclear. In this study, we used cultured
      neonatal rat cardiomyocytes to investigate the effect of BNP on MCU during
      reperfusion, the well-characterized pathological process of heart diseases. Our
      results demonstrated that treatment with BNP protected cardiomyocytes from
      apoptosis against I/R injury. Further investigation of underlying mechanisms
      revealed that BNP could partly prevent opening of mitochondrial calcium uniporter
      during I/R. And these mechanisms were associated with BNP-attenuated dissipation
      of mitochondrial membrane potential (Deltapsi(m)), generation of reactive oxygen
      species (ROS). BNP also increased the level of anti-apoptotic Bcl-2 protein,
      decreased the expressions of pro-apoptotic Bax and Smac/DIABLO. In summary, we
      demonstrated that BNP exerts protective functions within reperfusion by blocking
      mitochondrial calcium uniporter. Our findings also suggested that
      phosphatidylinositol 3-kinase (PI3K) dependent pathway may be involved in the
      actions of BNP.

PMID- 20149573
TI  - [Telemedicine: an unfruitful experience of tele-expertise in nephrology].
AB  - INTRODUCTION: We developed a new system of medical tele-expertise to improve
      detection and care of chronic renal failure by way of a better communication
      between general practitioners and specialists. It has been known for long that
      the incidence of chronic renal failure is increasing while cost of its treatment
      is very high. Unfortunately, late referral of patients with kidney diseases
      remains around 30%. Our goal was to help physicians to get access to
      nephrologists, hence to improve the cure of renal diseases. An early treatment of
      nephropathies may avoid the evolution to the stage of dialysis. METHODS: We
      created a website with the technical support of the firm Unimedecine. It allowed
      a secure and fast exchange of medical data, all about the case of a one patient.
      RESULTS: General practitioners seemed enthusiastic, but at the end, only a few of
      them did use the website. The number of connexion remained low throughout a 3
      year experience. Questions were about advices but no progressive nephropathy was
      discovered. The cost of the website was a prohibitive 75 000 euros for 3 years.
      Therefore, we had no choice that to close the experience. DISCUSSION:
      Telemedicine needs juridical rules and specific finances to work on a long run.

PMID- 20149574
TI  - Differences of knee anthropometry between Chinese and white men and women.
AB  - Whether there are differences in knee anthropometry between Asian and white knees
      remains unclear. Three-dimensional knee models were constructed using computed
      tomography or magnetic resonance imaging of healthy Chinese and white subjects.
      The morphologic measurements of the femur included mediolateral, anteroposterior
      dimensions, and aspect ratio. The tibial measurements included mediolateral,
      medial/lateral anteroposterior dimension, aspect ratio, and posterior slope of
      medial/lateral plateau. The results showed that Chinese knees were generally
      smaller than white knees. In addition, the femoral aspect ratio of Chinese
      females was significantly smaller than that of white females (1.24 +/- 0.04 vs
      1.28 +/- 0.06). Tibial aspect ratio differences between Chinese and white males
      (1.82 +/- 0.07 vs 1.75 +/- 0.11), though significant, were likely a reflection of
      differences in knee size between races. These racial differences should be
      considered in the design of total knee arthroplasty prosthesis for Asian
      population.

PMID- 20149575
TI  - Magnetic resonance imaging findings in painful metal-on-metal hips: a prospective
      study.
AB  - Metal artifact reduction sequence magnetic resonance imaging findings are
      reported in a prospective series of 31 patients with unexplained painful metal-on
      metal (MOM) hips. The abnormalities identified were fluid collection (20
      patients), solid mass (2 patients), moderate to severe muscle atrophy (23
      patients), and muscle edema (8 patients). In conclusion, soft tissue lesions and
      muscle atrophy appear to be prevalent in unexplained painful MOM hips. Metal
      artifact reduction sequence magnetic resonance imaging may be useful to diagnose
      and monitor at-risk hips but requires validation in well-functioning MOM hips
      before it can guide clinical decision making.

PMID- 20149576
TI  - Wound drainage after metal-on-metal hip arthroplasty secondary to presumed
      delayed hypersensitivity reaction.
AB  - An emerging concern with metal-on-metal total hip arthroplasty is metal-induced
      hypersensitivity. Currently, this is a diagnosis of exclusion in patients with
      groin pain after metal-on-metal total hip arthroplasty. We describe a patient
      presenting nearly a year after arthroplasty with incisional drainage. Infection
      was presumed; but preoperative studies were nondefinitive, and the wound was
      explored. The operative cultures were negative; the histology revealed
      lymphocytic vasculitis. The patient recovered uneventfully after exchange to a
      metal polyethylene bearing couple. We believe that metal-induced hypersensitivity
      should be considered with draining wounds with this bearing couple if infection
      cannot be proven.

PMID- 20149577
TI  - Complications after minimally invasive total knee arthroplasty as compared with
      traditional incision techniques: a meta-analysis.
AB  - The primary objective of our meta-analysis was to compare the incidence of
      complications between minimally invasive surgery and standard total knee
      arthroplasty (TKA) approaches. We reviewed randomized controlled trials comparing
      minimally invasive TKA to standard TKA. After testing for publication bias and
      heterogeneity, the data were aggregated by random effects modeling. Our primary
      outcome was the number of complications. Our secondary outcomes were alignment
      outliers, Knee Society Function scores, and Knee Society Knee scores. The
      combined odds ratios for complications for the minimally invasive surgery group
      and alignment outliers were 1.58 (95% confidence interval, 1.01-2.47; P < .05)
      and 0.79 (95% confidence interval, 0.34-1.82; P = .58), respectively. The
      standard difference in means for Knee Society scores was no different between
      groups. Minimally invasive knee surgery should be approached with caution.

PMID- 20149578
TI  - Visual loss after orthopedic procedures.
AB  - Perioperative visual loss (PVL) is a very rare and unpredictable complication of
      surgery performed at distance from the visual pathways, mostly after spine or
      cardiac procedures. We report 6 consecutive patients with PVL after routine
      orthopedic procedures (osteosynthesis for complex fracture of the femur [2],
      total hip arthroplasty [2], hip prosthesis arthroplasty [1], bilateral
      simultaneous total knee arthroplasty [1]) and reviewed the literature on the
      subject. An ischemic optic neuropathy was diagnosed in all cases, and visual loss
      was bilateral in 5 of 6 patients. Partial visual improvement occurred in only 3
      of 11 eyes. No specific therapy is available for PVL. Postoperative visual
      disturbances should prompt without delay an ophthalmic evaluation because
      emergent correction of anemia, systemic hypotension, or hypovolemia might improve
      visual prognosis of PVL.

PMID- 20149579
TI  - Minimum 5-year follow-up of a cementless, modular, tapered stem in hip revision
      arthroplasty.
AB  - Hip revision surgery with a cementless tapered femoral component can provide
      axial and rotational stability in patients with compromised proximal bone stock.
      This study includes 90 cases revised with the Link MP (Waldemar Link, Hamburg,
      Germany) prosthesis. The median age at surgery was 72 (38-89) years. Aseptic
      loosening (70%) and periprosthetic fracture (22%) were common indications for
      surgery. Sixty-three patients (70%) were followed clinically with a median of 6
      (5-11) years of follow-up. All other patients were followed through the Swedish
      Hip Register. The 5-year survival rate was 98% with stem removal and 90% with any
      reoperation as the end point. Complications included hip dislocation in 17 (19%)
      patients. The median Harris hip score was 78 (16-100) points, and the median
      radiographic stem migration was 2.7 mm at follow-up.

PMID- 20149580
TI  - Uncemented total knee arthroplasty: 2-year follow-up of 100 knees with a rotating
      platform, cruciate-retaining design.
AB  - Review of the literature shows mixed results regarding uncemented total knee
      arthroplasty (TKA). To our knowledge, there are no reports of results for
      uncemented TKA that incorporates a cruciate-retaining and rotating platform
      design. It is theorized that these design features could decrease the stress at
      the bone-implant interface. This study reports results on 100 uncemented TKAs at
      a minimum of 2-year follow-up. Average Knee Society clinical score improved from
      52.9 to 95.1; average Knee Society functional score improved from 60.5 to 82.0.
      Ninety-eight percent of patients had excellent and 2% had good results based on
      Knee Society scores. There was 99% implant survival; 1 patient required revision
      of a loose tibial component after a motor vehicle accident. The promising short
      term results support the continued use of this implant and suggest a prospective
      randomized study comparing cemented vs uncemented TKA of this design is
      warranted.

PMID- 20149581
TI  - Influence of acetabular cup rim design on the contact stress during edge loading
      in ceramic-on-ceramic hip prostheses.
AB  - The purpose of the study was to investigate the contact stresses in 3 different
      acetabular cup rim designs (new, worn, chamfer) during edge loading, after
      microseparation of ceramic on ceramic hip prostheses. A 3-dimensional finite
      element analysis was conducted for a 28-mm diameter alumina ceramic bearing with
      a radial clearance of 40 MUm using a normal load of 2500 N under edge loading. At
      a separation distance of 250 MUm, the maximum tensile stress in the "new" design
      was of similar magnitude to the flexural strength of the alumina material that
      supports the localized breakdown (stripe wear) of the acetabular cup surface
      observed clinically. Introducing a 2.5-mm radius chamfer should reduce the
      maximum tensile stress in the region of 60%.

PMID- 20149583
TI  - Retrieval analysis of femoral zirconium components in total knee arthroplasty:
      preliminary results.
AB  - Safety of oxidized zirconium (OxZr) in total knee arthroplasty (TKA) has been
      supported by biomechanical, clinical, and radiologic data. Retrieved OxZr femoral
      components and corresponding polyethylene (PE) inserts were examined to rule out
      patterns leading to early failure. Sixteen retrieved TKA with an OxZr femoral
      component were included. The PE inlays were analyzed applying an established
      scoring system for wear and surface damage. Femoral components were screened for
      scratching, pitting, delamination, and striations. The prostheses were in situ
      for 16.4 +/- 11.9 months. The average wear and damage score for the tibial PE
      inserts was 36.0 +/- 12.7. The average score in the visual analysis of the OxZr
      femoral components was 1.3 +/- 1.3. The data presented in this study did not show
      major wear of the PE in TKA using OxZr components. In this cohort, there were no
      failures directly related to this implant.

PMID- 20149582
TI  - A prospective evaluation of 2 different pain management protocols for total hip
      arthroplasty.
AB  - Pain management after total hip arthroplasty has improved dramatically in the
      past decade. However, most protocols use opioid medications for pain control. In
      the current study, 100 patients were prospectively selected to receive a
      traditional narcotic-based patient-controlled analgesia protocol or a nonnarcotic
      oral protocol for pain management after primary total hip arthroplasty. Therapy
      programs were similar for both groups. Postoperatively, patients were followed
      daily for opioid use, medication adverse effects, pain control, and overall
      satisfaction. The nonnarcotic oral group showed lower mean pain scores during the
      first 24 hours after surgery. The satisfaction rate was high in both groups. Both
      protocols provided adequate pain control after total hip arthroplasty; the
      nonnarcotic pain management protocol resulted in significantly decreased opioid
      consumption and fewer adverse effects.

PMID- 20149584
TI  - Ginger extract reduces delayed gastric emptying and nosocomial pneumonia in adult
      respiratory distress syndrome patients hospitalized in an intensive care unit.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of ginger extract
      on delayed gastric emptying, developing ventilator-associated pneumonia, and
      clinical outcomes in adult respiratory distress syndrome (ARDS). MATERIALS AND
      METHODS: Thirty-two ARDS patients who were dependent on mechanical ventilation
      and fed via nasogastric tube were studied. After enrollment, patients were
      randomized to 2 groups. The control group received 1 g of coconut oil as placebo,
      and the study group received 120 mg of ginger extract. The amount of feeding
      tolerated at the first 48 hours of feeding, amount of feeding tolerated during
      the entire study period, nosocomial pneumonia, number of intensive care unit
      (ICU)-free days, number of ventilator-free days, and mortality were evaluated
      during 21 days of intervention. RESULTS: There was a significant difference
      between the ginger group and the control group in the amount of feeding tolerated
      at the first 48 hours of enteral feeding (51% vs 57%, P < .005). There was a
      trend toward a decrease in pneumonia in the ginger group (P = .07). The overall
      in-ICU mortality was 15.6%, with no significant difference in the 2 groups. The
      number of ventilator-free days and that of ICU-free days were lower in the
      control group compared with the ginger group (P = .04 and P = .02). CONCLUSION:
      This study showed that gastric feed supplementation with ginger extract might
      reduce delayed gastric emptying and help reduce the incidence of ventilator
      associated pneumonia in ARDS.

PMID- 20149585
TI  - Effect of head rotation on overlap and relative position of internal jugular vein
      to carotid artery in infants and children: a study of the anatomy using
      ultrasonography.
AB  - PURPOSE: The aim of this study was to evaluate the influence of head rotation on
      the relative anatomy of internal jugular vein (IJV) and carotid artery (CA) in
      infants and children. MATERIALS AND METHODS: Two hundred pediatric patients (26.5
      +/- 23.3 months old) who were undergoing elective surgery were eligible for this
      consecutive and prospective study. Using 2-dimensional ultrasound, the amount of
      overlap and the relative position of the 2 vessels were compared between heads in
      the neutral position and in 90 degrees of rotation. RESULTS: The mean percentage
      overlap of CA by IJV in the neutral position increased significantly as the head
      was rotated to the right (23.3% vs 39.2%) and left (35.3% vs 52.8%). The
      incidence of lateral positioning of IJV to CA decreased significantly when the
      head was rotated (40% vs 21% in right, 26.5% vs 10.5% in left). The right IJV is
      associated with less overlap of the CA than the left, regardless of head
      position. CONCLUSIONS: The head should be kept in as near a neutral position as
      possible because the overlap increased by head rotation in both sides. In
      addition, the right IJV should be preferred because of less CA overlap and more
      lateral positioning than the left.

PMID- 20149586
TI  - Prospective evaluation of a decision support system for setting inspired oxygen
      in intensive care patients.
AB  - PURPOSE: The aim of the study was to prospectively evaluate a decision support
      system for its ability to provide appropriate suggestions of inspired oxygen
      fraction in intensive care patients comparing with levels used by clinicians in
      attendance. MATERIALS AND METHODS: Thirteen mechanically ventilated patients were
      studied in an intensive care unit where up to 4 experiments were performed during
      2 consecutive days. Inspired oxygen fraction was selected in each experiment by
      both the decision support system and attending clinicians, and each selection was
      evaluated by measuring arterial oxygen saturation. RESULTS: Median (interquartile
      range [range]) changes in inspired oxygen fraction from baseline level by
      attending clinicians and the decision support system were 0.00 (-0.05 to 0.00 [
      0.10 to 0.05]) and -0.03 (-0.07 to 0.01 [-0.16 to 0.12]), respectively. Clinician
      ranges of inspired oxygen fraction and arterial oxygen saturation were 0.25 to
      0.70 and 0.92 to 0.99, respectively. Decision support system ranges of inspired
      oxygen fraction and arterial oxygen saturation were 0.26 to 0.54 and 0.94 to
      0.99, respectively. CONCLUSIONS: The decision support system selects appropriate
      levels of inspired oxygen fraction in intensive care patients and could be used
      for automatic frequent assessment of patients, freeing the focus of clinicians to
      concentrate on more challenging therapy.

PMID- 20149587
TI  - Prognostic factors of mortality in patients with community-acquired bloodstream
      infection with severe sepsis and septic shock.
AB  - PURPOSE: The purpose of the study was to determine the independent risk factors
      on mortality in patients with community-acquired severe sepsis and septic shock.
      METHODS: A single-site prospective cohort study was carried out in a medical
      surgical intensive care unit in an academic tertiary care center. One hundred
      twelve patients with community-acquired bloodstream infection with severe sepsis
      and septic shock were identified. Clinical, microbiologic, and laboratory
      parameters were compared between hospital survivors and hospital deaths. RESULTS:
      One-hundred twelve patients were included. The global mortality rate was 41.9%,
      44.5% in septic shock and 34.4% in severe sepsis. One or more comorbidities were
      present in 66% of patients. The most commonly identified bloodstream pathogens
      were Escherichia coli (25%) and Staphylococcus aureus (21.4%). The proportion of
      patients receiving inadequate antimicrobial treatment was 8.9%. By univariate
      analysis, age, Acute Physiology and Chronic Health Evaluation II score, at least
      3 organ dysfunctions, and albumin, but neither microbiologic characteristics nor
      site of infection, differed significantly between survivors and nonsurvivors.
      Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.13; 95%
      confidence interval, 1.06-1.21) and albumin (odds ratio, 0.34; 95% confidence
      interval, 0.15-0.76) were independent risk factors associated with global
      mortality in logistic regression analysis. CONCLUSION: In addition to the
      severity of illness, hypoalbuminemia was identified as the most important
      prognostic factor in community-acquired bloodstream infection with severe sepsis
      and septic shock.

PMID- 20149588
TI  - Practical experiences and in vitro and in vivo validation studies with a new
      gastric tonometric probe in human adult patients.
AB  - PURPOSE: This study provides practical experiences with a new, simple, balloon
      free gastric tonometric probe (probe) and reports the results of simultaneous in
      vitro and in vivo measurements with a conventional, ballooned gastric air
      tonometer (catheter) and the new device. MATERIALS AND METHODS: Ten healthy
      volunteers and 50 anesthetized surgical patients with different American Society
      of Anesthesiologists (ASA) scores, scheduled for neurologic, orthopedic, trauma,
      and cardiac operations, were enrolled in the study. The values of 60 in vitro
      and, in 12 surgical patients, 101 in vivo paired Pco(2) measurements--performed
      simultaneously with the new tonometric probe and the catheter that was connected
      to a Tonocap monitor--were compared. The tolerability of the measurement with the
      new probe was examined, and the results of gastric tonometry and, in surgical
      cases, the gastric tonometric, end-expiratory, and arterial Pco(2) values were
      registered. The results were evaluated by analysis of variance test. The data of
      the in vivo paired measurements were evaluated by Bland-Altman analysis. RESULTS:
      The use of the probe proved to be well tolerated and easily applicable in the
      studied cases. The results of 20 measurements obtained in healthy volunteers and
      those of 520 measurements in the surgical cases correspond to the data obtained
      with the classical methods published in the medical literature. During in vitro
      paired measurements, there was a good agreement between the data obtained with
      the 2 methods; however, in the in vivo studies, the results of measurements
      performed with the probe were mostly higher. CONCLUSIONS: The differences between
      the results obtained with the 2 methods might have been caused by the quicker
      equilibration property of the probe and by the fundamental differences between
      the 2 methods. The new probe seems to be applicable for routine human
      measurements.

PMID- 20149589
TI  - The 4Ts scoring system for heparin-induced thrombocytopenia in medical-surgical
      intensive care unit patients.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is commonly considered but
      rarely confirmed in critically ill patients. The 4Ts score (Thrombocytopenia,
      Timing of thrombocytopenia, Thrombosis, and oTher reason) might identify
      individual patients at risk of having this disorder. OBJECTIVE: The aim of the
      study was to evaluate the value of the 4Ts HIT score in comparison with the
      serotonin-release assay (SRA) in critically ill patients. METHODS: This study
      describes the combined results of 3 prospective studies enrolling critically ill
      patients who were investigated for HIT if platelets fell to less than 50 x
      10(9)/L or if platelet counts decreased to less than 50% of the value upon
      intensive care unit admission. We confirmed HIT by a positive platelet SRA. We
      assigned a 4Ts score blinded to SRA results to all 50 patients investigated for
      HIT; those with positive SRA results were scored in duplicate. RESULTS: Of 528
      patients, 50 (9.5%) were investigated for HIT; 39 (78%) of 50 (64%-88%) of these
      patients were scored as "low probability" by 4Ts score and none had a positive
      SRA. Of 49 patients who underwent SRA testing because of thrombocytopenia, only 2
      (4.1%; 0.5-14.0) had a positive SRA (1 with a moderate 4Ts score and 1 with a
      high 4Ts score). Therefore, the overall incidence of HIT confirmed by SRA was 2
      (0.4%) of 528 (0.04%-1.4%). CONCLUSIONS: Significant thrombocytopenia during
      heparin administration occurred in 9.5% of critically ill patients, but HIT was
      confirmed in only 4.1% of those undergoing testing, for an overall incidence of
      0.4%. A low 4Ts score occurred in 78% of patients investigated for HIT; none of
      these patients had a positive SRA. We conclude that HIT is uncommon in critically
      ill patients and that the 4Ts score is worthy of further evaluation in this
      patient population.

PMID- 20149590
TI  - Troponin-I as a prognosticator of mortality in severe sepsis patients.
AB  - PURPOSE: The purpose of this retrospective study was to evaluate cardiac troponin
      I (cTnI) as a 28-day mortality prognosticator and predictor for a drotrecogin
      alfa (activated) (DrotAA) survival benefit in recombinant human activated Protein
      C Worldwide Evaluation in Severe Sepsis patients. METHODS: Cardiac troponin-I was
      measured using the Access AccuTnI Troponin I assay (Beckman Coulter, Fullerton,
      CA). There were 598 patients (305 DrotAA, 293 placebo) with baseline cTnI data
      (cTnI negative [<0.06 ng/mL], n = 147; cTnI positive [>or=0.06 ng/mL], n = 451).
      RESULTS: Cardiac troponin-I-positive patients were older (mean age, 61 vs 56
      years; P = .002), were sicker (mean Acute Physiology and Chronic Health
      Evaluation II, 26.1 vs 22.3; P < .001), had lower baseline protein C levels (mean
      level, 49% vs 56%; P = .017), and had higher 28-day mortality (32% vs 14%, P <
      .0001) than cTnI-negative patients. Elevated cTnI was an independent
      prognosticator of mortality (odds ratio, 2.020; 95% confidence interval, 1.153
      3.541) after adjusting for other significant variables. Breslow-Day interaction
      test between cTnI levels and treatment was not significant (P = .65). CONCLUSION:
      This is the largest severe sepsis study reporting an association between elevated
      cTnI and higher mortality. Cardiac troponin-I elevation was not predictive of a
      survival benefit with DrotAA treatment.

PMID- 20149591
TI  - Scoring systems in acute pancreatitis: which one to use in intensive care units?
AB  - PURPOSE: The aim of the study was to assess and compare the efficacy of various
      scoring systems in predicting the severity and outcome of patients with acute
      pancreatitis (AP) admitted in intensive care unit (ICU). METHODS: Prospective,
      single institution review of 55 consecutive AP patients admitted in ICU during a
      2-year period. Disease severity scores and mortality predictions were calculated
      using the collected data in the first 48 hours of ICU admission for Ranson and
      Glasgow scores and in the first 24 hours for other scores. RESULTS: Forty-two
      patients (76.4%) developed severe pancreatitis. Intensive care unit and 30-day
      mortality was 18.2% and 27.3%, respectively. Use of mechanical ventilation (MV)
      was an independent predictor of outcome on multivariate analysis with lack of MV
      being protective (adjusted odds ratio, 0.003; 95% confidence interval [CI],
      0.00001-0.67; P = .04). All scoring systems had comparable accuracy in predicting
      severity and 30-day mortality, but sequential organ failure assessment (SOFA)
      score had greater efficacy with its area under curve for predicting severity and
      30-day mortality being 0.81 (95% CI, 0.69-0.92) and 0.93 (95% CI, 0.85-0.99),
      respectively. Sensitivity and specificity (SOFA score, >4) was 76.2% and 69.2%,
      respectively, for predicting severity, and sensitivity and specificity (SOFA
      score, >8) was 86.7% and 90%, respectively, for predicting 30-day mortality.
      CONCLUSIONS: Use of MV is an independent predictor of outcome in AP patients
      admitted to ICU. Although all scoring systems had reliable accuracy in predicting
      severity and outcome, SOFA score performed better with additional advantages of
      easy applicability and timely assessment.

PMID- 20149592
TI  - The S/Z ratio: a simple and reliable clinical method of evaluating laryngeal
      function in patients after intubation.
AB  - OBJECTIVES: 1. To determine the consequences of prolonged intubation on laryngeal
      function. 2. To evaluate simple clinical criteria or tests that could alert the
      clinician to potential laryngeal pathology requiring ear, nose, and
      throat/otolaryngology (ENT) referral. DESIGN: A prospective case series. SETTING:
      A surgical intensive care unit in a tertiary academic hospital in Cape Town,
      South Africa. PARTICIPANTS: Thirty-two patients who had undergone a period of
      translaryngeal intubation for a period greater than 12 hours. MAIN OUTCOME
      MEASURES: 1. Patient subjective voice change rating. 2. Clinician assessment of
      laryngeal function. 3. S/Z ratio. 4. Presence of laryngeal pathology on
      endoscopic assessment of the larynx. RESULTS: Upon initial evaluation within 6
      hours of extubation, 26 (81%) of patients exhibited symptomatic laryngeal
      dysfunction. At this stage, 13 (40%) had S/Z ratios greater than 1.4. The degree
      of dysfunction as described by subjective scoring and the S/Z ratio was
      proportional to the duration of intubation. After 24 hours, 23 (72%) patients'
      voices had improved subjectively; and the S/Z ratio exceeded 1.4 in just 6
      patients (19%). Of these 6 patients, 4 exhibited laryngeal pathology on flexible
      nasoendoscopy. These 4 patients were followed up over 1 year, and 1 patient was
      ultimately offered a vocal cord medialization procedure. The S/Z ratio is 100%
      sensitive and 93% specific, with an accuracy of 93.75%, in diagnosing laryngeal
      pathology requiring ENT referral. CONCLUSIONS: 1. A period of laryngeal
      intubation carries signification risk of laryngeal dysfunction. Most, but not
      all, dysfunction resolves within 24 hours. 2. Residual laryngeal pathology can be
      reliably and simply screened for by the use of the S/Z ratio. We recommend that
      patients with an S/Z ratio greater than 1.4 more than 24 hours after extubation
      require ENT referral for laryngoscopy.

PMID- 20149593
TI  - Autism spectrum disorder diagnoses in Stockholm preschoolers.
AB  - The aims of this study were to estimate prevalence rates of children with autism
      spectrum disorder (ASD) diagnoses in a cohort of 6-year-old children with birth
      year 2002, referred to the Autism Centre for Young Children, serving the whole of
      Stockholm county and on the basis of the available data discuss clinical aspects
      of assessment, habilitation and follow-up. Records of 142 of a total of 147 (123
      boys and 24 girls) identified children with ASD diagnoses were scrutinised with
      respect to type of diagnosis, cognitive level, other developmental disorders and
      medical/neurological disorders. The overall prevalence of such disorders was
      6.2/1000 (95% confidence interval 5.2-7.2/1000). The rates of learning
      disability/mental retardation, developmental delay without a specified cognitive
      level and normal intelligence constituted about one third, respectively. AS and
      atypical autism tended to be diagnosed more often at age 5-6 years while AD with
      learning disability/mental retardation was more often diagnosed at age 3-4 years.
      The awareness of ASDs has resulted in increasing numbers of children being
      diagnosed at young ages. We conclude that it is important to take into account
      these children's broader developmental profiles, need for repeated assessment of
      cognitive functions and follow-up over time and also the requirement for
      medical/neurological consideration and work-up.

PMID- 20149594
TI  - Diffuse late gadolinium enhancement by cardiovascular magnetic resonance predicts
      significant intraventricular systolic dyssynchrony in patients with non-ischemic
      dilated cardiomyopathy.
AB  - BACKGROUND: Left ventricular dyssynchrony and myocardial fibrosis are common
      findings in patients with nonischemic dilated cardiomyopathy (NDCM). The aim of
      this study was to investigate the association between myocardial fibrosis and
      intraventricular systolic dyssynchrony (DYS-sys) in patients with NDCM. METHODS:
      Thirty-nine patients with NDCM and sinus rhythm were enrolled. Intraventricular
      DYS-sys was evaluated using Doppler tissue imaging, and cardiac fibrosis was
      assessed with cardiovascular magnetic resonance imaging with a 17-segment cardiac
      model. Each segment was graded on a 2-point scale (segmental fibrosis score): 0 =
      absence of late gadolinium enhancement, and 1 = presence of late gadolinium
      enhancement. A cardiac fibrosis index was calculated as 17/(17 - sum of fibrotic
      segments). Receiver operating characteristic analysis was performed to determine
      the utility of the cardiac fibrosis index to predict intraventricular systolic
      dyssynchrony. RESULTS: Patients with DYS-sys had larger left atrial size (P =
      .004) and left ventricular end-systolic (P = .028) and end-diastolic (P = .034)
      volumes and lower tricuspid annular Doppler tissue imaging peak systolic
      velocities (P = .037) compared with patients without DYS-sys. A cardiac fibrosis
      index > or = 1.4 predicted significant DYS-sys with 92% sensitivity and 60%
      specificity (area under the receiver operating characteristic curve, 0.703; 95%
      confidence interval, 0.512-0.893; P = .035). Patients with cardiac fibrosis
      indexes > or = 1.4 (group 1) had larger left ventricular end-systolic (P = .044)
      and end-diastolic (P = .034) volumes than those with cardiac fibrosis indexes <
      1.4 (group 2). Nine of 11 patients (82%) in group 1 and 6 of 28 patients (21%) in
      group 2 had significant DYS-sys (Pearson's chi(2) = 12.169, P < .0001). Logistic
      regression analysis revealed that cardiac fibrosis index > or = 1.4 (odds ratio,
      11.2; 95% confidence interval, 1.72-71.4; P = .012) was an independent predictor
      of DYS-sys. CONCLUSION: Patients with NDCM and prominent cardiac fibrosis have
      significant DYS-sys. The cardiac fibrosis index is a useful tool to predict DYS
      sys.

PMID- 20149595
TI  - Traumatic tricuspid regurgitation caused by myocardial laceration: a three
      dimensional echocardiographic study.
AB  - A 19-year-old man was admitted for severe traumatic tricuspid regurgitation (TR)
      4 months after a traffic accident. Transthoracic echocardiography revealed severe
      TR, with an abnormal chordal structure. Three-dimensional echocardiography showed
      widely lacerated right ventricular endocardium involving many subvalvular
      components. In this case of traumatic TR, three-dimensional echocardiography was
      useful not only for its diagnosis but also in providing important information for
      surgical decision making.

PMID- 20149596
TI  - Evidence that Yaa-induced loss of marginal zone B cells is a result of dendritic
      cell-mediated enhanced activation.
AB  - The development of systemic lupus is accelerated by the Yaa (Y-linked autoimmune
      acceleration) mutation, which is the consequence of a translocation of the
      telomeric end containing the Tlr7 gene from the X chromosome onto the Y
      chromosome. However, the loss of marginal zone (MZ) B cells, one of the Yaa
      linked cellular abnormalities, has previously been shown to be unrelated to the
      Tlr7 gene duplication, and the present study therefore aimed to investigate the
      mechanism responsible for MZ B-cell loss. Analyses of Yaa and non-Yaa C57BL/6
      male mice expressing an MD4 anti-HEL IgM transgene or those deficient in fms-like
      tyrosine kinase 3 ligand (FL) revealed that the proportion of MZ B cells in these
      Yaa mice was comparable to that of the respective non-Yaa control mice. Notably,
      the activation of MZ B cells was compromised in both of these transgenic model
      systems, due to the absence of cognate antigens or the impaired development of
      dendritic cells, respectively. These results contrasted with the loss of MZ B
      cells in non-Yaa mice treated with FL and the lack of accumulation of MZ B cells
      in Yaa mice treated with a B-cell survival factor, BAFF. Taken together, our
      results suggest that the persistent and enhanced activation of Yaa-bearing
      hyperactive MZ B cells by dendritic cells is responsible for the loss of this B
      cell subset in Yaa mice.

PMID- 20149597
TI  - Treatment modalities of TMJ ankylosis: experience in Delta Nile, Egypt.
AB  - The study reports the authors' experience in managing TMJ ankylosis in Delta
      Nile, Egypt (1995-2006) and compares the surgical modalities used. 101 patients
      (109 joints) were reviewed in this retrospective study. Pre- and postoperative
      assessment included history, radiological and physical examination, and mouth
      opening. Age, sex, aetiology, joint(s) affected, surgical modality, complications
      and follow up periods were evaluated. Various types (fibrous, fibro-osseous and
      bony) of TMJ ankylosis were diagnosed; trauma was the commonest aetiology. The
      patients' age range was 2-41 years, 62% were female, and the follow up period
      ranged from 14 to 96 months. Average mouth opening was significantly increased
      from 5.3mm pre-operatively to 32.9 mm 12 months postoperatively (P=0.0001).
      Marked improvement in mouth opening was documented when the ramus-joint complex
      was reconstructed using distraction osteogenesis (34.7 mm), costochondral graft
      (34.4mm) and Surgibone (34.6mm). Gap arthroplasty showed least satisfactory mouth
      opening compared with other techniques (P=0.001). Minor and major complications
      were encountered in 33% of cases, including 5% recurrence rate. Early release of
      TMJ ankylosis; reconstruction of the ramus height with distraction osteogenesis
      or bone grafting combined with interpositional arthroplasty, followed by vigorous
      physiotherapy is successful for managing TMJ ankylosis.

PMID- 20149598
TI  - Implant-retained nasal prosthesis for reconstruction of large rhinectomy defects:
      the Salisbury experience.
AB  - The authors report their experience with 34 patients who had large full thickness
      nasal defects reconstructed with an implant-retained prosthesis. Their technique
      of modifying post-rhinectomy defects is described and factors influencing implant
      success are evaluated. 111 implants were placed to retain a nasal prosthesis.
      Age, sex and tumour histology did not affect the outcome. Smoking, extent of
      rhinectomy, use of radiotherapy (pre- and post-implant), hyperbaric oxygen,
      length and location of the implant and type of retention (bar/magnets) influenced
      implant success. The overall success rate was 89% (99/111); 94% in patients who
      did not receive radiotherapy and 86% in those who did. The prosthesis was in
      place in all patients (100%) at the time of last follow up. Post-rhinectomy
      defect modification enables adequate access for safe placement of long implants
      with good primary stability and helps the maintenance of good hygiene (further
      enhanced by the use of skin grafts). The authors think implant-retained
      prosthesis is a reliable option for reconstructing large full thickness
      rhinectomy defects. They suggest their technique of modifying the defect, use of
      long implants and magnets for retention is responsible for the high success rate
      of implants used to retain a nasal prosthesis.

PMID- 20149599
TI  - The role of the disc in the healing of displaced subcondylar fracture in the
      growing period: an experimental study in rats.
AB  - The purpose of this study was to evaluate the role of the disc in the healing of
      condylar fractures in the growing period. 40 growing and adult male Wistar rats
      were randomized into 4 equal groups: growing rats suffering condylar fracture
      with disc damage; growing rats suffering condylar fracture without disc damage;
      adult rats suffering condylar fracture with disc damage; adult rats suffering
      condylar fracture without disc damage. 3 months after the operation all animals
      were killed and the outcomes were compared using mandible deviation measure, body
      weight evaluation and histological observation. In growing rats, when the disc
      was undamaged maintaining its relation to the condyle head, even though the
      condylar fractured fragment was displaced, the condyle healed and recovered
      almost to normality in 3 months. In the same condyle fracture form, once the disc
      was damaged and lost the normal relation with the condyle head, the outcome was
      unfavourable. The occurrence of damage to the disc and its attachment to the
      condyle head are important factors in the healing of condyle fractures in the
      growing period.

PMID- 20149600
TI  - Lennox-Gastaut syndrome in adulthood: clinical and EEG features.
AB  - PURPOSE: We performed a retrospective study to investigate seizure, EEG, social
      and cognitive outcome in adult LGS subjects. METHODS: We retrospectively
      evaluated 27 LGS patients aged 40-59 years. We assessed in particular the
      evolution of different seizure types and EEG findings, as well as cognitive and
      social outcome. RESULTS: During the early stages of the disease, all patients
      presented tonic seizures (TS) during wakefulness and sleep, 20/27 had atypical
      absences (AA), more rarely other seizure types. EEG showed slow background
      activity in 21/27 patients, diffuse slow spike-wave discharges (DSSW) during
      wakefulness in 22/27, and bursts of diffuse fast rhythms (DFR) in sleep in all
      patients. At last observation, 11 patients only had TS during wakefulness, but
      all still presented TS during sleep; AA persisted in 6 patients. EEG showed
      normal BA in 12/27 patients; only 7/27 still presented DSSW. On the contrary,
      sleep EEG showed the persistence of DFR in all. A moderate to severe cognitive
      impairment was observed in 26/27 patients. CONCLUSIONS: In adult LGS patients TS
      during sleep remain the major seizure type; moreover, a standard waking EEG may
      be normal. Thus, polysomnography represents the most important mean of
      investigation also in adult LGS patients.

PMID- 20149602
TI  - Antibiotic resistance of bacterial biofilms.
AB  - A biofilm is a structured consortium of bacteria embedded in a self-produced
      polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms
      cause chronic infections because they show increased tolerance to antibiotics and
      disinfectant chemicals as well as resisting phagocytosis and other components of
      the body's defence system. The persistence of, for example, staphylococcal
      infections related to foreign bodies is due to biofilm formation. Likewise,
      chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is
      caused by biofilm-growing mucoid strains. Characteristically, gradients of
      nutrients and oxygen exist from the top to the bottom of biofilms and these
      gradients are associated with decreased bacterial metabolic activity and
      increased doubling times of the bacterial cells; it is these more or less dormant
      cells that are responsible for some of the tolerance to antibiotics. Biofilm
      growth is associated with an increased level of mutations as well as with quorum
      sensing-regulated mechanisms. Conventional resistance mechanisms such as
      chromosomal beta-lactamase, upregulated efflux pumps and mutations in antibiotic
      target molecules in bacteria also contribute to the survival of biofilms.
      Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy
      and they can be treated by chronic suppressive therapy. A promising strategy may
      be the use of enzymes that can dissolve the biofilm matrix (e.g. DNase and
      alginate lyase) as well as quorum-sensing inhibitors that increase biofilm
      susceptibility to antibiotics.

PMID- 20149601
TI  - Evidence for genetic modifiers other than filaggrin mutations in X-linked
      ichthyosis.

PMID- 20149603
TI  - Mutation frequency in antibiotic-resistant and -susceptible isolates of
      Streptococcus pneumoniae.
AB  - Development of multiple antibiotic resistance in Streptococcus pneumoniae
      typically involves either mutation or transformation at several well-separated
      chromosomal loci. We postulated that this series of genetic events would be more
      likely to occur in organisms with deficient DNA repair mechanisms. Investigation
      of 27 antibiotic-resistant or -susceptible clinical isolates of S. pneumoniae
      revealed a broad range of mutation frequencies, but no isolate was as mutable as
      a mismatch repair (MMR)-deficient laboratory isolate. No correlation was observed
      between antibiotic resistance and higher mutation frequency. Examination of a
      further 180 clinical isolates using a newly developed rapid screen method also
      failed to identify any isolates with a mutation frequency as high as the MMR
      deficient control strain. We argue that there is currently no clear evidence of a
      distinct population of mutators among clinical pneumococci.

PMID- 20149604
TI  - Enhanced stabilization of cloudy emulsions with gum Arabic and whey protein
      isolate.
AB  - Cloudy emulsions are oil-in-water (O/W) emulsions normally prepared as
      concentrates, further diluted, per request, into the final beverage. The cloudy
      emulsion provides flavor, color, and cloud (turbidity) to the soft drink. These
      systems are stabilized by emulsifiers and/or amphiphilic polysaccharides. Cloudy
      emulsions based on naturally occurring food grade emulsifiers were studied in the
      present work. Two charged natural biopolymers, whey protein isolate (WPI) and gum
      Arabic (GA), are interacted in aqueous solution to form charge-charge
      interactions improving the emulsion stability. The emulsions were high sheared
      (Microfluidizer) and characterized by particle size distribution analysis (DLS),
      optical centrifugation (LUMiFuge), optical microscopy observations, and turbidity
      measurements. Emulsions obtained from 10wt% of 3:1wt. ratio WPI:GA, at pH 7
      (10wt% canola oil) show better stability than emulsions stabilized by GA or WPI
      alone. The droplet sizes were smaller than 1microm and did not grow significantly
      during 1 month of incubation at 25 degrees C. The D-limonene-based emulsion
      droplets were larger (> 2microm) than those made with vegetable oils immediately
      after preparation and underwent significant droplet size increase (coalescence)
      within 1 month (>8 microm). The emulsion with turbidity suitable as a cloudy
      emulsion was composed of 3wt% WPI:GA (3:1) and 20wt% canola oil.

PMID- 20149605
TI  - Biliary intervention aggravates cholestatic liver injury, and induces hepatic
      inflammation, proliferation and fibrogenesis in BDL mice.
AB  - Obstructive cholestasis occurs in various clinical situations, whose pathological
      process is complex and not well known. The present study was initiated to display
      the complex and multifaceted pathological process caused by obstructive
      cholestasis in bile duct-ligated mice. Adult mice were bile-duct-ligated or sham
      operated, and serum and liver tissues were collected at the indicated time
      points. Automatic biochemical analyzer was used to monitor serum biochemical
      index; TUNEL, HE staining, immunohistochemistry and Real-time PCR were employed
      to evaluate liver apoptosis, necrosis, inflammation, as well as proliferation and
      fibrosis. Our results demonstrated that obstructive cholestasis led to elevated
      serum biochemical indicators, with ALT peaking at day 3, indicative of acute
      hepatic dysfunction. Meanwhile, the number of TUNEL-positive cells increased
      significantly, and by 2 weeks, mild to moderate necrosis became apparent in BDL
      mouse livers, which consequently aggravated hepatic inflammatory responses as was
      demonstrated by increased expression of KC-1, MIP-2, ICAM-1 and MPO in BDL mouse
      livers. Moreover, proliferative hepatocytes around periportal areas, manifested
      by enhanced cell mitosis and elevated expression of proliferative markers such as
      PCNA and Ki67, increased significantly after BDL, while increased CK-19-positive
      cells in bile ducts indicated bile duct hyperplasia. By 2 weeks, numerous alpha
      SMA-positive cells and Sirius-stained collagen were observed, indicative of
      hepatic stellate cells (HSC) activation and fibrogenesis. In conclusion, biliary
      intervention led to a multifaceted hepatic pathological process characterized by
      aggravated liver injury and inflammatory reaction with enhanced cellular
      proliferation and fibrogenesis.

PMID- 20149606
TI  - Expression of aquaporin 1 (AQP1) in human synovitis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disorder characterized by synovial
      proliferation (synovitis), articular cartilage and subchondral bone degradation
      as well as joint swelling. Joint swelling and edema often accompany pannus
      formation and chronic joint inflammation in RA. We have recently shown that human
      chondrocytes and synoviocytes express aquaporin 1 (AQP1) water channels and that
      AQP1 is upregulated in RA cartilage. Clinical evidence suggests that joint
      swelling and edema accompany the chronic inflammation observed in synovial joints
      of RA patients. Therefore we hypothesized that AQP1 water channels may be
      involved in joint swelling and synovial edema formation. To test this hypothesis,
      we performed immunostaining of normal and human synovitis tissue microarrays
      (TMAs) to investigate whether the expression of AQP1 water channels is altered in
      the synovium in synovitis. Immunohistochemistry revealed that AQP1 is expressed
      in synovial micro-vessels and synoviocytes from normal joints (n=20 normal
      subjects). Semi-quantitative histomorphometric analysis of AQP1 expression in the
      TMAs revealed upregulation of the membrane protein in the synovium derived from
      RA (n=10) and psoriatic arthritis (n=8) patients. These results indicate a
      potential role for synovial AQP1 and other aquaporins in joint swelling and the
      vasogenic edema fluid formation and hydrarthrosis associated with synovial
      inflammation. Future experiments will need to determine whether the expression of
      other aquaporins is altered in synovitis.

PMID- 20149607
TI  - Profiling type I collagen gene expression in growing mandibular structures.
AB  - We conducted a temporal gene expression analysis with type I collagen in the
      coronoid process, alveolar process and mandibular angle of the rat. We observed
      gene expression cross-sectionally across different important physiological time
      points in the rat postnatal life in order to observe in which developmental stage
      mandibular development mainly occur. This study indicates prominent type I
      collagen expression at day 10 postpartum in the mandibular ramus and at day 21 in
      the alveolar process. These findings correspond well with previously obtained
      data from proliferation studies in facial bone suggesting that craniofacial
      growth in the rat occurs mainly between days 10 and 21.

PMID- 20149608
TI  - Alterations in the vascular architecture of the dorsal root ganglia in a rat
      neuropathic pain model.
AB  - An alteration in the structural arrangement of blood vessels identified by RECA
      immunohistochemistry was studied in a rat L4 dorsal root ganglia (L4-DRG)
      neuropathic pain model. We compared a three-dimensional (3-D) reconstruction of
      the vascular architecture surrounding bodies of the primary sensory neurons in
      the L4-DRG of naive rats with that of rats that had surgically undergone
      unilateral sciatic nerve ligature. Rhodamine-conjugated dextran (Fluoro-Ruby) was
      used for retrograde labelling of neurons, the axons of which had been injured by
      nerve ligature. In contrast to DRG from naive rats and contralateral DRG from
      operated rats, an increased proportion of RECA+ vascular area and the appearance
      of nest-like arrangements of blood vessels around neuronal bodies with injured
      axons were observed in L4-DRG ipsilateral to the sciatic nerve ligature. Fractal
      analysis confirmed a higher degree of vascular branching, irregularity, and
      tortuosity in L4-DRG related with sciatic nerve injury. The results suggest that
      nerve injury induces changes in vascular architecture in associated DRG.

PMID- 20149609
TI  - The origin and early development of the nasal septum in human embryos.
AB  - Based on scanning electron microscopic dissections of human embryos and fetuses
      of the sixth to the twelfth week (Carnegie stages 16-23 and early fetus), the
      origin of the nasal septum was studied. The findings show that the nasal septum
      does not grow downwards. It is derived from the tissue between the primary
      choanae: as such, its anlage is present from the very beginning. Its contact and
      fusion with the palatal shelves is made possible by the elevation of the palatal
      shelves from the vertical into the horizontal position, as the tongue descends.

PMID- 20149610
TI  - (-)-Epigallocatechin-3-gallate downregulates Pg-P and BCRP in a tamoxifen
      resistant MCF-7 cell line.
AB  - We investigated the anticancer effect of EGCG treatment on a breast carcinoma
      cell line resistant to tamoxifen (MCF-7Tam cells). As there are no reports about
      the molecular mechanisms implicated in EGCG treatment of tamoxifen resistant
      breast carcinoma cells, we studied the effects of EGCG treatment on three plasma
      membrane proteins that are involved in the mechanism of drug-resistance:
      Multidrug Resistance Protein (MRP1), P-glycoprotein (P-gp) and Breast Cancer
      Resistance Protein (BCRP). EGCG treatment (10-100 microg/ml for 24-72 hours)
      caused cell growth inhibition and dose-dependent apoptosis: after 100 microg/ml
      EGCG treatment for 24 hours, Bax expression increased and Bcl2 expression
      decreased (p<0.05). Coherently, Annexin V-FITC apoptosis assay detected a
      significant increase in labelled cells (p<0.05). EGCG did not affect MRP1: in
      contrast, 100 microg/ml EGCG administration caused P-gp decrease to 53% of
      control cells (p<0.001) and this effect was not due to downregulation of P-gp
      gene expression. EGCG induced P-gp decrease even when MG132, a strong proteasome
      inhibitor, was given together with EGCG to MCF-7Tam cells. EGCG treatment also
      inhibited BCRP activity: mRNA transcription and protein level did not change
      after treatment, but mitoxantrone test demonstrated a strong inhibition of BCRP
      activity (p<0.001). In conclusion, the present results showed that EGCG could
      down-regulate the activity of two molecules that play a key role in drug
      metabolism and transport and that are highly expressed in tamoxifen resistant
      breast carcinoma cells. The interaction of EGCG and drugs used in the therapy of
      estrogen sensitive breast carcinoma ought to be subject of studies and the
      potential use of EGCG in drug-resistant diseases ought to be better considered.

PMID- 20149611
TI  - Antiasthmatic effect of Nigella sativa in airways of asthmatic patients.
AB  - In the present study, the antiasthmatic (bronchodilatory) effect of the boiled
      extract of Nigella sativa in the airways of asthmatic patients was examined. The
      bronchodilatory effects of 50 and 100 mg/kg of boiled extract in comparison with
      6 mg/kg theophylline were studied on 15 asthmatic patients. Pulmonary function
      tests (PFTs) including forced expiratory volume in one second (FEV(1)), peak
      expiratory flow (PEF), maximal mid expiratory flow (MMEF), maximal expiratory
      flow at 75, 50 and 25% of the FVC (MEF(75), MEF(50), and MEF(25,) respectively)
      and specific airway conductance (sGaw) were measured before administration and
      repeated , 30, 60, 90 120, 150, and 180 min after administration of the oral
      extract and theophylline. The results showed that the extract caused significant
      increases in all measured pulmonary function tests (PFTs), in most time
      intervals, (p<0.05 to p<0.001). However, the increase in FEV(1), MMEF and MEF(50)
      due to both doses of boiled extract and increase in MEF(75) and MEF(25) due to
      its lower doses were significantly lower than those of theophylline (p<0.05 to
      p<0.001). The onset of brochodilatory effect of extract was similar to that of
      theophylline beginning 30 min, and the effect of extract decline after 150 min
      following administration similar to the effect of theophylline. The effect of
      both doses of the extract was also significantly less than that of salbutamol at
      30 minutes post administration (p<0.001 for all cases). The results of the
      present study showed that Nigella sativa has a relatively potent antiasthmatic
      effect on asthmatic airways. However, the effects of boiled extract of this plant
      on most measured PFTs was less than those of theophylline at concentrations used.

PMID- 20149612
TI  - Topical anti-inflammatory potential of Physalin E from Physalis angulata on
      experimental dermatitis in mice.
AB  - The anti-inflammatory effect of physalin E, a seco-steroid isolated from Physalis
      angulata L. was evaluated on acute and chronic models of dermatitis induced by 12
      O-tetradecanoyl-phorbol-13-acetate (TPA) and oxazolone, respectively, in mouse
      ear. The changes in ear edema/thickness, production of pro-inflammatory cytokines
      (TNF-alpha and IFN-gamma), myeloperoxidase (MPO) activity, and histological and
      immunohistochemical findings were analysed, as indicators of dermal inflammation.
      Similar to dexamethasone, topically applied Physalin E (0.125; 0.25 and 0.5
      mg/ear) potently inhibited the TPA and oxazolone-induced dermatitis, leading to
      substantial reductions in ear edema/thickness, pro-inflammatory cytokines, and
      MPO activity. These effects were reversed by mifepristone, a steroid antagonist
      and confirmed by immunohistochemical and histopathological analysis. The data
      suggest that physalin E may be a potent and topically effective anti-inflammatory
      agent useful to treat the acute and chronic skin inflammatory conditions.

PMID- 20149613
TI  - Ardipusilloside I purified from Ardisia pusilla competitively binds VEGFR and
      induces apoptosis in NCI-H460 cells.
AB  - The present study was to evaluate the effects of Ardipusilloside I isolated from
      Ardisia pusilla on the growth, vascular endothelial growth factor receptor
      (VEGFR) expression and apoptosis of NCI-H460 cell line by MTT, ELISA and flow
      cytometer, respectively. The docking assay between Ardipusilloside I and VEGFR
      was studied by Sybyl/Sketch module. The change of microstructure was observed by
      transmission electron microscope (TEM). DNA fragmentation was visualized by
      agarose gel electrophoresis. The protein expression of Bax and Bcl-2 was detected
      by immunohistochemistry (IHC). A series of changes were observed in NCI-H460 cell
      treated by Ardipusilloside I, including microstructure, DNA fragmentation,
      protein expression of VEGFR, Bax and Bcl-2. The results showed Ardipusilloside I
      had a good docking with VEGFR and could inhibit growth and induce apoptosis of
      NCI-H460 cell in a dose-dependent manner. Cell cycle was significantly stopped at
      the G(1) phase. Under electronic microscope, the morphology of NCI-H460 cell
      treated with Ardipusilloside I showed nuclear karyopycnosis, chromatin
      agglutination and typical apoptotic body. VEGFR and Bcl-2 expression were
      decreased and Bax expression was increased. In conclusion, all these results
      demonstrate that Ardipusilloside I has a good docking with VEGFR and has an
      inhibitory effect on growth of NCI-H460 cell and can induce its apoptosis.

PMID- 20149614
TI  - Enhancing effects of a chromone glycoside, eucryphin, isolated from Astilbe
      rhizomes on burn wound repair and its mechanism.
AB  - We previously reported that three compounds isolated from Astilbe thunbergii
      rhizomes accelerated burn wound healing. Among the three substances, eucryphin
      enhanced burn wound healing most strongly; however, the biological mechanisms of
      eucryphin are not yet well understood and here we examined the effects on
      chemokine, growth factor, and cytokine productions in in vivo and in vitro
      experiments. We have set burn wounds on the backs of mice and topically applied
      either vehicle alone or vehicle containing low doses of eucryphin to the burn
      wound. We examined the effects of eucryphin on chemokine, cytokine, and growth
      factor production at the wound site and in various cells. Eucryphin (10(-4) to
      10(-8)% ointment) facilitated burn wound repair compared to the vehicle control.
      Eucryphin (100 ng per wound) increased IL-1beta, MCP-1, VEGF, and TGF-beta1
      levels in the exudates from the wound area. Eucryphin increased VEGF, TGF-beta1,
      and HIF-1alpha expression levels in keratinocytes. These findings suggest that
      the enhancement of burn wound healing by eucryphin might be due to promotional
      angiogenesis during skin wound repair as a result of the stimulation of VEGF and
      TGF-beta1 production caused by the increase in HIF-1alpha expression in
      keratinocytes.

PMID- 20149616
TI  - The role of NOD-like Receptors in shaping adaptive immunity.
AB  - Not only does the innate immune system represent the first line of defense
      against invading pathogens, but it is also responsible for instructing
      appropriate adaptive immune responses. Pattern recognition receptors (PRR) detect
      the presence of invading pathogens and are paramount in innate instruction of the
      adaptive immune response. A diverse class of PRRs, the NOD-like Receptors (NLR),
      has recently been implicated in the regulation of processes ranging from anti
      tumor immunity to the adjuvant action of aluminum hydroxide. In this review we
      will highlight many of the recent findings in the NLR field with a particular
      focus on NLR influence of adaptive immune responses.

PMID- 20149615
TI  - Antigen processing via autophagy--not only for MHC class II presentation anymore?
AB  - T cells monitor intracellular and extracellular protein composition via
      proteolytic products that are displayed to them on major histocompatibility
      complex (MHC) molecules. For this purpose it has been documented that MHC class
      II molecules, which were originally thought to just display lysosomal products of
      endocytosed proteins to CD4(+) helper T cells, can also present intracellular
      substrates of autophagic pathways. This has triggered the interest of
      immunologists into the role of autophagy in antigen processing in general, and
      recently additional autophagic mechanisms for intracellular and extracellular
      antigen processing onto MHC class I molecules for presentation to CD8(+)
      cytolytic T cells have been revealed. Here, I will review the contribution of
      autophagy for MHC class I and class II antigen processing and presentation to T
      cells.

PMID- 20149617
TI  - Burden of pulmonary arterial hypertension in Germany.
AB  - This study aimed to describe health care provision, resource consumption and
      related costs, as well as treatment patterns and quality of life in adult
      patients with pulmonary arterial hypertension (PAH) in Germany. Data for this
      retrospective and prospective cost-of-illness-study were derived from hospitals,
      general practitioners and patients. Costs were evaluated from the perspective of
      third party payer and patient. Quality of life data were collected by using three
      validated instruments. A total of 167 patients were enrolled at 10 hospitals.
      Time period from first occurrence of symptoms to confirmed diagnosis of PAH was
      2.3 years on average. Mean number of GP visits was 1.5 per patient per month, and
      within 15 months, inpatient stays were reported for 50% of patients. The ratio of
      combination therapy to single-drug therapy for endothelin receptor antagonists,
      phosphodiesterase-5-inhibitor and prostacyclin analogues increased significantly
      during 15 months. Treatment costs were, on average, euro47,400 per patient per
      year, arising mainly from drugs. Compared to the general population, quality of
      life of PAH patients was considerably impaired. This is the first study which
      evaluated aspects of the medical and economic consequences of PAH based on a
      large cohort of PAH patients in Germany.

PMID- 20149618
TI  - High fat diet-induced animal model of age-associated obesity and osteoporosis.
AB  - Osteoporosis and obesity remain a major public health concern through its
      associated fragility and fractures. Several animal models for the study of
      osteoporotic bone loss, such as ovariectomy (OVX) and denervation, require unique
      surgical skills and expensive set up. The challenging aspect of these age
      associated diseases is that no single animal model exactly mimics the progression
      of these human-specific chronic conditions. Accordingly, to develop a simple and
      novel model of post menopausal bone loss with obesity, we fed either a high fat
      diet containing 10% corn oil (CO) or standard rodent lab chow (LC) to 12-month
      old female C57Bl/6J mice for 6 months. As a result, CO fed mice exhibited
      increased body weight, total body fat mass, abdominal fat mass and reduced bone
      mineral density (BMD) in different skeletal sites measured by dual energy X-ray
      absorptiometry. We also observed that decreased BMD with age in CO fed obese mice
      was accompanied by increased bone marrow adiposity, up-regulation of peroxisome
      proliferator-activated receptor gamma, cathepsin k and increased proinflammatory
      cytokines (interleukin 6 and tumor necrosis factor alpha) in bone marrow and
      splenocytes, when compared to that of LC fed mice. Therefore, this appears to be
      a simple, novel and convenient age-associated model of post menopausal bone loss,
      in conjunction with obesity, which can be used in pre-clinical drug discovery to
      screen new therapeutic drugs or dietary interventions for the treatment of
      obesity and osteoporosis in the human population.

PMID- 20149620
TI  - Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory
      cytokines in cultured macrophage-like cells via the inhibition of the activation
      of nuclear factor kappaB through the repression of IKKalpha/beta phosphorylation.
AB  - Vitamin K is essential for blood coagulation and bone metabolism in mammals. This
      vitamin functions as a cofactor in the posttranslational synthesis of gamma
      carboxyglutamic acid (Gla) from glutamic acid residues. However, other functions
      of vitamin K have been reported recently. We previously found that vitamin K
      suppresses the inflammatory reaction induced by lipopolysaccharide (LPS) in rats
      and human macrophage-like THP-1 cells. In this study, we further investigated the
      mechanism underlying the anti-inflammatory effect of vitamin K by using cultures
      of LPS-treated human- and mouse-derived cells. All the vitamin K analogues
      analyzed in our study exhibited varied levels of anti-inflammatory activity. The
      isoprenyl side chain structures, except geranylgeraniol, of these analogues did
      not show such activity; warfarin did not interfere with this activity. The
      results of our study suggest that the 2-methyl-1,4-naphtoquinone ring structure
      contributes to express the anti-inflammatory activity, which is independent of
      the Gla formation activity of vitamin K. Furthermore, menaquinone-4, a form of
      vitamin K2, reduced the activation of nuclear factor kappaB (NFkappaB) and
      inhibited the phosphorylation of IKKalpha/beta after treatment of cells with LPS.
      These results clearly show that the anti-inflammatory activity of vitamin K is
      mediated via the inactivation of the NFkappaB signaling pathway.

PMID- 20149619
TI  - The skeletal muscle transcript profile reflects accommodative responses to
      inadequate protein intake in younger and older males.
AB  - Inadequate protein intake initiates adverse changes in skeletal muscle function
      and structure (i.e., an accommodative response). mRNA level changes due to short
      term inadequate dietary protein might be an early indication of subsequent
      accommodation. The aims of this study were to assess the effects of dietary
      protein and the diet-by-age interaction on the skeletal muscle transcriptome.
      Twelve younger (21-43 y) and 10 older (63-79 y) men completed three controlled
      feeding trials with protein intakes of 0.50 (LPro: lower protein), 0.75 (MPro:
      medium protein) and 1.00 g protein.kg body weight-1.day-1 (HPro: higher protein).
      A fasting state biopsy was taken on Day 12 of each trial. Global changes in
      transcript levels were assessed with Affymetrix genechips and expression patterns
      determined using self-organizing maps. Nine hundred fifty-eight transcripts were
      differentially expressed (P<.05) by diet and 853 had a diet-by-age interaction
      (P<.05). The results for diet alone revealed that LPro was associated with up
      regulation of transcripts related to ubiquitin-dependent protein catabolism and
      muscle contraction and LPro and MPro resulted in up-regulation of transcripts
      related to apoptosis and down-regulation of transcripts related to cell
      differentiation, muscle and organ development, extracellular space and responses
      to stimuli and stress. The diet-by-age effect on protein modification transcripts
      was consistent with the older males being less responsive to anabolic stimuli
      (lower protein synthesis at HPro) and more responsive to a catabolic state
      (protein breakdown at LPro). Changes in skeletal muscle mRNA levels in younger
      and older males to protein intake near or below the recommended dietary allowance
      are indicative of an early accommodative response.

PMID- 20149621
TI  - Hydroxytyrosol protects against oxidative damage by simultaneous activation of
      mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal
      pigment epithelial cells.
AB  - Studies in this laboratory have previously shown that hydroxytyrosol, the major
      antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment
      epithelial cells from oxidative damage induced by acrolein, an environmental
      toxin and endogenous end product of lipid oxidation, that occurs at increased
      levels in age-related macular degeneration lesions. A proposed mechanism for this
      is that protection by hydroxytyrosol against oxidative stress is conferred by the
      simultaneous activation of two critically important pathways, viz., induction of
      phase II detoxifying enzymes and stimulation of mitochondrial biogenesis.
      Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with
      acrolein. The protective effects of hydroxytyrosol on key factors of
      mitochondrial biogenesis and phase II detoxifying enzyme systems were examined.
      Hydroxytyrosol treatment simultaneously protected against acrolein-induced
      inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome
      proliferator-activated receptor coactivator 1 alpha (PPARGC1alpha) in ARPE-19
      cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes,
      including gamma-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine
      dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide
      dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes,
      while the activation of PPARGC1alpha led to increased protein expression of
      mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial
      complexes. These results suggest that hydroxytyrosol is a potent inducer of phase
      II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary
      supplementation of hydroxytyrosol may contribute to eye health by preventing the
      degeneration of retinal pigment epithelial cells induced by oxidative stress.

PMID- 20149622
TI  - Molecular mechanisms involved in the enhancement of mitochondrial malate
      dehydrogenase activity by calcitriol in chick intestine.
AB  - Mitochondrial malate dehydrogenase (mMDH) from the intestine is the NAD-linked
      oxidoreductase of the tricarboxylic acid cycle with the highest activity and
      response to vitamin D treatment in vitamin D-deficient chicks (-D). The aim of
      this study was to elucidate potential molecular mechanisms by which
      cholecalciferol or calcitriol enhances the activity of this enzyme. One group of
      animals used was composed of -D and -D treated with cholecalciferol or with
      calcitriol. A second group consisted of -D and -D supplemented with high Ca(2+)
      diet. A third group included chicks receiving either a normal or a low Ca(2+)
      diet. In some experiments, animals were injected with cycloheximide. Data showed
      that either vitamin D (cholecalciferol or calcitriol) or a low Ca(2+) diet
      increases mMDH activity. High Ca(2+) diet did not modify the intestinal mMDH
      activity from -D. The mMDH activity from -D remained unaltered when duodenal
      cells were exposed to 10(-8) mol/L calcitriol for 15 min. The enhancement of mMDH
      activity by calcitriol was completely abolished by simultaneous cycloheximide
      injection to -D. mMDH mRNA levels, detected by RT-PCR, indicate that calcitriol
      did not affect gene expression. In contrast, Western blots show that calcitriol
      enhanced the protein expression. In conclusion, calcitriol stimulates intestinal
      mMDH activity by increasing protein synthesis. No response of mMDH activity by
      rapid effects of calcitriol or activation through increment of serum Ca(2+) was
      demonstrated. Consequently, ATP production would be increased, facilitating the
      Ca(2+) exit from the enterocytes via the Ca(2+)-ATPase and Na(+)/Ca(2+)
      exchanger, which participate in the intestinal Ca(2+) absorption.

PMID- 20149623
TI  - Butyrate reduced lipopolysaccharide-mediated macrophage migration by suppression
      of Src enhancement and focal adhesion kinase activity.
AB  - Macrophage motility is vital in innate immunity. Lipopolysaccharide (LPS)
      mediated macrophage migration requires the enhancement of Src expression and
      enzymatic activity, which can be regulated by inducible nitric oxide synthase
      (iNOS). As a major short-chain fatty acid with histone deacetylase (HDAC)
      inhibitor activity, butyrate exerts anti-inflammatory effect by regulating the
      expression of cytokines. However, the influence of butyrate on macrophage
      movement was vague. In this study, we observed that butyrate inhibited migration
      of both RAW264.7 and rat peritoneal macrophages elicited by LPS. Unlike its
      myeloid relatives (i.e. Lyn, Fgr and Hck) whose expression was almost unaltered
      in the presence or absence of butyrate in LPS-treated macrophages, LPS-mediated
      Src induction was greatly suppressed by butyrate and that could be attributable
      to reduced level of the src transcript. Similar phenomenon was also detected in
      LPS-treated macrophages exposed to another HDAC inhibitor, trichostatin A (TSA).
      Consistent with the indispensability of iNOS in promoting macrophage mobilization
      via Src up-regulation and the activation of both Src and FAK, we did observe
      concomitant decrement of iNOS, Src and the suppressed activity of Src and FAK in
      butyrate- or TSA-pretreated macrophages following LPS exposure. These results
      imply that by virtue of reduction of Src, butyrate could effectively hamper LPS
      triggered macrophage locomotion.

PMID- 20149624
TI  - Vitamin E decreases endogenous cholesterol synthesis and apo-AI-mediated
      cholesterol secretion in Caco-2 cells.
AB  - Intestine is the gateway for newly absorbed tocopherols. This organ also plays a
      crucial role in cholesterol metabolism. Because tocopherols are known to impact
      cholesterol metabolism in the liver, we hypothesized that tocopherols could also
      modulate cholesterol metabolism in the intestine. This study aimed to verify this
      hypothesis and to unveil the mechanisms involved, using Caco-2 cells as a model
      of the human intestinal cell. Both alpha- and gamma-tocopherol significantly
      (P<.05) decreased endogenous cholesterol synthesis and apo-AI-mediated
      cholesterol secretion in Caco-2 cells. Tocopherols down-regulated (P<.05) up to
      half of the genes involved in the cholesterol synthesis pathway, together with
      CYP27A1, which is involved in oxysterol production. The activity of this enzyme,
      as well as the levels of intracellular oxysterols, was significantly diminished
      by tocopherols. Finally, tocopherols significantly reduced ABCA1 mRNA levels in
      Caco-2 cells. We conclude that tocopherols impair the endogenous synthesis and
      apo-AI-mediated secretion of cholesterol in Caco-2 cells. This effect involves a
      down-regulation of genes involved in the cholesterol synthesis pathway, resulting
      in down-regulation of CYP27A1 which, in turn, diminishes oxysterol
      concentrations. The outcome is a decrease of LXR activity, resulting in down
      regulation of ABCA1. These data reinforce the effect of alpha- and gamma
      tocopherol on cholesterol metabolism via gene expression regulation.

PMID- 20149625
TI  - N-3 polyunsaturated fatty acids regulate lipid metabolism through several
      inflammation mediators: mechanisms and implications for obesity prevention.
AB  - Obesity is a growing problem that threatens the health and welfare of a large
      proportion of the human population. The n-3 polyunsaturated fatty acids (PUFA)
      are dietary factors that have potential to facilitate reduction in body fat
      deposition and improve obesity-induced metabolic syndromes. The n-3 PUFA up
      regulate several inflammation molecules including serum amyloid A (SAA), tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in hepatocytes and
      adipocytes. Actions of these inflammation mediators resemble those of n-3 PUFA in
      the modulation of many lipid metabolism-related genes. For instance, they both
      suppress expressions of perilipin, sterol regulatory element binding protein-1
      (SREBP-1) and lipoprotein lipase (LPL) to induce lipolysis and reduce
      lipogenesis. This review will connect these direct or indirect regulating
      pathways between n-3 PUFA, inflammation mediators, lipid metabolism-related genes
      and body fat reduction. A thorough knowledge of these regulatory mechanisms will
      lead us to better utilization of n-3 PUFA to reduce lipid deposition in the liver
      and other tissues, therefore presenting an opportunity for developing new
      strategies to treat obesity.

PMID- 20149626
TI  - The yin and yang of B cells in graft rejection and tolerance.
AB  - Various lineages of B cells are being increasingly recognized as important
      players in the etiology and prognosis of both acute and chronic graft rejection.
      The role of immature, chronically activated B cells, as efficient antigen
      presenting cells, supporting recalcitrant cell-mediated graft rejection and late
      lineage B cells driving humoral rejections, is being increasingly recognized.
      This review captures the recent literature on this subject and discusses the
      various roles of the B cell in renal graft rejection and conversely, also in
      graft tolerance, both in animal and human studies. In addition, novel therapies
      targeting specific B-cell lineages in graft rejection are also discussed, with a
      view to developing more targeted therapies for graft rejection.

PMID- 20149627
TI  - Survey of carbonization facilities for municipal solid waste treatment in Japan.
AB  - The operations of carbonization facilities for municipal solid waste treatment in
      Japan were examined. Input waste, system processes, material flows, quality of
      char and its utilization, fuel and chemical consumption, control of facility
      emissions, and trouble areas in facility operation were investigated and
      analyzed. Although carbonization is a technically available thermochemical
      conversion method for municipal solid waste treatment, problems of energy
      efficiency and char utilization must be solved for carbonization to be
      competitive. Possible solutions include (1) optimizing the composition of input
      waste, treatment scale, organization of unit processes, operational methods, and
      quality and yield of char on the basis of analysis and feedback of long-term
      operating data of present operating facilities and (2) securing stable char
      demands by linking with local industries such as thermal electric power
      companies, iron manufacturing plants, and cement production plants.

PMID- 20149628
TI  - Significant enhancement in the power-conversion efficiency of chlorophyll co
      sensitized solar cells by mimicking the principles of natural photosynthetic
      light-harvesting complexes.
AB  - Dye-sensitized solar cells (DSSCs) are similar to natural photosynthesis in the
      initial processes involving in light-harvesting and charge separation. In order
      to mimic those natural photosynthetic systems mainly containing multiple
      pigments, six different chlorophyllous sensitizers have been isolated from
      natural photosynthetic organism or synthesized based on natural photosynthetic
      precursors, and used for fabricating DSSCs. These dye sensitizers can be placed
      into three classes, i.e., a-type, b-type, or c-type, based on the structural
      similarity to their analogs of the natural photosynthesis pigments chlorophylls
      a, b, and c. We succeeded in demonstrating homogeneous co-sensitization among
      these analogues when these were present together on mesoporous TiO2 films, and we
      measured the photovoltaic performance of the resulting chlorophyll-sensitized
      solar cells. Significantly enhanced power-conversion efficiencies (eta) were
      achieved with DSSCs based on co-sensitization of a chlorophyll a derivative with
      a chlorophyll b or c derivative. A highest power-conversion efficiency of up to
      5.4% has been obtained. These results suggest that it is possible to apply
      multiple pigments and the energy transfer mechanism from natural photosynthetic
      systems in fabricating high-efficiency DSSCs.

PMID- 20149629
TI  - Scanning electrochemical microscopy assay of DNA based on hairpin probe and
      enzymatic amplification biosensor.
AB  - A novel scheme for scanning electrochemical microscopy (SECM) assay of DNA based
      on hairpin probe and enzymatic amplification biosensor was described. In this
      method, streptavidin-horseradish peroxidase (HRP) was captured by double-stranded
      DNA (ds-DNA) modified gold substrate via biotin-streptavidin interaction after
      hybridization of target DNA to the immobilized hairpin probe functioned with a
      biotin at its 3' end. In the presence of H2O2, hydroquinone (H2Q) was oxidized to
      benzoquinone (BQ) at the modified substrate surface through the HRP catalytic
      reaction, and the generated BQ corresponding to the amount of target DNA was
      reduced in solution by a SECM tip. The resulting reduction current allowed
      concentration detection of target DNA and SECM imaging of hybridization between
      the target DNA and the immobilized hairpin probe. The detection limit of this
      method was as low as 17 pM for complementary target DNA and it had good
      selectivity to discriminate between the complementary sequence and one containing
      base mismatches.

PMID- 20149630
TI  - Optical tracking of a stress-responsive gene amplifier applied to cell-based
      biosensing and the study of synthetic architectures.
AB  - A synthetic regulatory construct based on a two-stage amplifying promoter cascade
      is applied to whole-cell biosensing. Green fluorescent protein (GFP) and red
      fluorescent protein (RFP) enable two-component tracking of the response event,
      enabling the system to exhibit increased sensitivity, a lower limit of detection,
      and a unique optical density-free assessment mode. Specifically, the recA and tac
      promoters are linked by the LacI repressor in Escherichia coli, where DNA-damage
      activates the recA promoter and the up-regulation of GFP and LacI proteins. LacI
      represses the tac promoter, down-regulating the otherwise constitutive mCherry
      transcription. The response of the construct was compared with two singly tagged,
      conventional recA promoter-reporter constructs: recA::gfpmut3.1 and
      recA::mCherry. Using a miniature LED-based flow-through optical detector
      developed for remote sensing applications, limits of detection for the dual
      reporter construct reached as low as 0.1 nM MMC. By comparison, single-ended
      reporters recA::mCherry and recA::gfpmut3.1 achieved best limits of detection of
      0.25 nM and 2.0 nM, respectively. An approach to three-component optical
      analysis, based on a system of detectors with coupled calibration equations
      enables accurate assessments of the red fluorescence, green fluorescence, and
      biomass of sensor cell suspensions. The system approach is effective at
      overcoming interferences caused by optically dense samples and overlapping
      fluorescence spectra. Such a technique may be useful in studying the biological
      mechanisms which underlie the synthetic regulatory device of this work and
      others.

PMID- 20149631
TI  - Fast sampling for quantitative microbial metabolomics.
AB  - Targeted metabolomics, aimed at the study of metabolic reaction networks and
      their regulation in vivo, is a rapidly emerging field in systems biology.
      Obtaining proper quantitative snapshots of the microbial metabolome requires fast
      sampling, immediate quenching of enzymatic activity, separation of exometabolome
      and endometabolome, complete metabolite extraction from the cells, and reliable
      high-throughput analysis methods. This review addresses the current state of the
      art of rapid sampling and quenching for microbial metabolomics. Several robust
      and reliable rapid sampling devices have been developed. Various quenching and
      separation procedures have been proposed and applied, but with respect to the
      reliability of the different methods the literature is contradictory. To date a
      reliable universal method applicable to different microbial species is still
      lacking.

PMID- 20149632
TI  - Microbial ecology of foodborne pathogens associated with produce.
AB  - The recent recognition of fresh fruits and vegetables as major vehicles of
      foodborne illness has led to increased research on mechanisms by which enteric
      pathogens contaminate and persist on and in this non-host environment.
      Interactions between foodborne pathogens and plants as well among the naturally
      occurring microbial communities contribute to endophytic and epiphytic
      colonization. Scientific findings are just beginning to elucidate the mechanisms
      that contribute to colonization of produce. This review addresses current
      knowledge as well as future research needed to increase our understanding of the
      microbial ecology of enteric pathogens on fruits and vegetables.

PMID- 20149633
TI  - Microbial antagonists to food-borne pathogens and biocontrol.
AB  - Application of natural antimicrobial substances (such as bacteriocins) combined
      with novel technologies provides new opportunities for the control of pathogenic
      bacteria, improving food safety and quality. Bacteriocin-activated films and/or
      in combination with food processing technologies (high-hydrostatic pressure, high
      pressure homogenization, in-package pasteurization, food irradiation, pulsed
      electric fields, or pulsed light) may increase microbial inactivation and avoid
      food cross-contamination. Bacteriocin variants developed by genetic engineering
      and novel bacteriocins with broader inhibitory spectra offer new biotechnological
      opportunities. In-farm application of bacteriocins, bacterial protective
      cultures, or bacteriophages, can decrease the incidence of food-borne pathogens
      in livestock, animal products and fresh produce items, reducing the risks for
      transmission through the food chain. Biocontrol of fungi, parasitic protozoa and
      viruses is still a pending issue.

PMID- 20149634
TI  - Development.

PMID- 20149635
TI  - Protein folding on the ribosome.
AB  - In living systems, polypeptide chains are synthesised on ribosomes, molecular
      machines composed of over 50 protein and nucleic acid molecules. As nascent
      chains emerge from the ribosomal exit tunnel and into the cellular environment,
      the majority must fold into specific structures in order to function. In this
      article we discuss recent approaches designed to reveal how such folding occurs
      and review our current knowledge of this complex self-assembly process.

PMID- 20149636
TI  - Virus particle maturation: insights into elegantly programmed nanomachines.
AB  - Similar modes of virus maturation have been observed in dsDNA bacteriophages and
      the structurally related herpes viruses and some type of maturation occur in most
      animal viruses. Recently a variety of biophysical studies of maturation
      intermediates of bacteriophages P22, lambda, and HK97 have suggested an energy
      landscape that drives the transitions and structure-based mechanisms for its
      formation. Near-atomic resolution models of subunit tertiary structures in an
      early intermediate of bacteriophage HK97 maturation revealed a remarkable
      distortion of the secondary structures when compared to the mature particle.
      Scaffolding proteins may induce the distortion that is maintained by quaternary
      structure interactions following scaffold release, making the intermediate
      particle metastable.

PMID- 20149637
TI  - Common variants in human CRC genes as low-risk alleles.
AB  - The genetic susceptibility to colorectal cancer (CRC) has been estimated to be
      around 35% and yet high-penetrance germline mutations found so far explain less
      than 5% of all cases. Much of the remaining variations could be due to the co
      inheritance of multiple low penetrant variants. The identification of all the
      susceptibility alleles could have public health relevance in the near future. To
      test the hypothesis that what are considered polymorphisms in human CRC genes
      could constitute low-risk alleles, we selected eight common SNPs for a pilot
      association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH
      Q324H) seemed to confer an increased risk of rectal cancer in homozygous status
      (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super
      controls', healthy individuals with no family history for cancer, also
      rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon
      and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05
      1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6
      P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The
      latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon
      patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study
      suggests that common variants in human CRC genes could constitute low-risk
      alleles.

PMID- 20149638
TI  - Prognostic significance and clinical relevance of the expression of the HER
      family of type I receptor tyrosine kinases in human laryngeal squamous cell
      carcinoma.
AB  - INTRODUCTION: The full clinical relevance of the expression pattern of HER family
      of type I receptor tyrosine kinases in laryngeal squamous cell carcinoma remains
      to be elucidated. We evaluated the clinical relevance of such parameter in our
      population. PATIENTS AND METHODS: This study examined the expression pattern of
      HER family receptor members by quantitative immunohistochemistry and the amount
      of the EGF binding sites by a radioligand binding assay, in the same group of 67
      LSCC patients, analysing the correlation between the expression of the four HER
      receptors and the clinical and prognostic parameters. RESULTS: HER1 levels
      inversely correlated with that of HER2-4, while HER2-4 directly correlated among
      them. Cox univariate analysis using HER1-4 values as continuous covariates
      indicated that HER1 expression was directly associated with the risk of death and
      relapse while that of HER2-4 was inversely associated with the risk of death.
      Among the patients with high HER1 expressing tumours, those with tumours co
      expressing HER2-4 showed a lower risk of death and relapse (in particular
      regional relapse) than those with tumours displaying a negative HER2-4 status.
      CONCLUSIONS: The evaluation of HER2-4 status adds more power to the prognostic
      role of HER1 detection. In the era of molecularly targeted therapy, the
      expression of HER family of receptor tyrosine kinases in LSCC may hold relevant
      clinical significance and turn out to be a key factor in prognostic assessment
      and in treatment planning.

PMID- 20149639
TI  - Rectal cancer surgery: a brief history.
AB  - In the last 250 years, the treatment of rectal cancer has changed dramatically.
      Once considered an incurable disease, combined modality therapy has improved
      mortality from 100% to less than 4% for locally advanced rectal cancer. This
      dramatic reduction paralleled surgical techniques based on a growing
      understanding of anatomy and disease pathology. In order to understand modern
      treatment, it is necessary to recognize the achievements of preceding surgeons.

PMID- 20149641
TI  - Use of chemometrics in the chemical and microbiological characterization of
      composts from agroindustrial wastes.
AB  - Physico-chemical, chemical and microbiological parameters were studied in a set
      of fifteen different composts elaborated with agroindustrial wastes using two
      different composting systems (turning and static pile composting). To carry out
      the chemometric evaluation, multivariate statistical analysis techniques, such as
      hierarchical cluster analysis (HCA) and factorial analysis (FA) were used.
      Composts obtained showed suitable physico-chemical and chemical properties for
      their use as organic amendment and a good maturity degree. HCA allowed to
      classify the organic materials mainly in four groups: cluster A, cluster B,
      cluster C and unclustered composts; also, this statistical tool showed the lack
      of influence of the composting system in the final characteristics of these
      composts. On the other hand, through FA, it was possible to identify the
      principal variables associated to the composting of agroindustrial wastes in four
      factors that explained 72.3% of the variability.

PMID- 20149640
TI  - The effect of the surface charge of hydrogel supports on thermophilic biohydrogen
      production.
AB  - The effect of the surface charge of different immobilizing hydrogels on
      biohydrogen production in batch cultures was investigated using a novel isolate
      associated to the genus Thermoanaerobacterium. Two crosslinked polysaccharide
      based hydrogels and two acrylic hydrogels were tested as polymeric carriers for
      cell adsorption. Immobilization improved both substrate conversion and hydrogen
      cumulative production compared to the suspended culture, and a yield of 1.9 mol
      H(2)/mol glucose was observed after 24h for alginate-supported cultures. Cationic
      carriers dramatically increased cell immobilization, leading to markedly faster
      kinetics of substrate degradation and hydrogen production in batch operation,
      with a peak of 3.6 mol H(2)/mol glucose for the acrylic hydrogel HM92.
      Accumulation of gaseous and acidic metabolites inhibited further H(2) production,
      shifting the carbon flow to reduced end-products and biomass synthesis.
      Preliminary tests showed that all the tested hydrogels had good durability and
      allowed hydrogen production on repeated batch runs.

PMID- 20149642
TI  - Optimization of enzymatic hydrolysis of steam-exploded corn stover by two
      approaches: response surface methodology or using cellulase from mixed cultures
      of Trichoderma reesei RUT-C30 and Aspergillus niger NL02.
AB  - To optimize enzymatic hydrolysis of steam-exploded corn stover (SECS), two
      approaches, response surface methodology (RSM) and utilization of the cellulase
      from mixed cultures of Trichoderma reesei RUT-C30 and Aspergillus niger NL02,
      were introduced in this work. The RSM, the first approach, was consisted of
      Plackett-Burman Design (PBD) and Central Composite Design (CCD). After the
      optimization of RSM, a model was proposed to predict the optimum value 79.6%
      confirmed by the experimental result 80.1%. Mixed culture of T. reesei and A.
      niger was found to be an effective method to enhance cellulolytic enzymes
      production. Using the cellulase from mixed culture to optimize enzymatic
      hydrolysis was the second approach. The yield of 85.6% was obtained by the second
      approach using 25IU/g glucan cellulase. The two approaches were compared and it
      was found that the second approach was a better one with higher hydrolysis yield
      and less enzyme dosage.

PMID- 20149643
TI  - Production of biofuels, limonene and pectin from citrus wastes.
AB  - Production of ethanol, biogas, pectin and limonene from citrus wastes (CWs) by an
      integrated process was investigated. CWs were hydrolyzed by dilute-acid process
      in a pilot plant reactor equipped with an explosive drainage. Hydrolysis
      variables including temperature and residence time were optimized by applying a
      central composite rotatable experimental design (CCRD). The best sugar yield
      (0.41g/g of the total dry CWs) was obtained by dilute-acid hydrolysis at 150
      degrees C and 6min residence time. At this condition, high solubilization of
      pectin present in the CWs was obtained, and 77.6% of total pectin content of CWs
      could be recovered by solvent recovery. Degree of esterification and ash content
      of produced pectin were 63.7% and 4.23%, respectively. In addition, the limonene
      of the CWs was effectively removed through flashing of the hydrolyzates into an
      expansion tank. The sugars present in the hydrolyzates were converted to ethanol
      using baker's yeast, while an ethanol yield of 0.43g/g of the fermentable sugars
      was obtained. Then, the stillage and the remaining solid materials of the
      hydrolyzed CWs were anaerobically digested to obtain biogas. In summary, one ton
      of CWs with 20% dry weight resulted in 39.64l ethanol, 45m(3) methane, 8.9l
      limonene, and 38.8kg pectin.

PMID- 20149644
TI  - Biotransformation of thianicotinyl neonicotinoid insecticides: diverse molecular
      substituents response to metabolism by bacterium Stenotrophomonas maltophilia
      CGMCC 1.1788.
AB  - The carbon atom that neighbors the tertiary amine attached to the 6-chloro-3
      pyridinylmethyl moiety is the key active site in the hydroxylation of the
      neonicotinoids imidacloprid and thiacloprid as well as in the demethylation of
      acetamiprid by Stenotrophomonas maltophilia CGMCC 1.1788. In this study,
      thianicotinyl neonicotinoid insecticides having diverse molecular substituents
      were biotransformed by S. maltophilia CGMCC 1.1788. The results indicated that
      the substitution of 6-chloropyridyl in imidacloprid with 2-chlorothiazol in
      imidaclothiz did not affect the hydroxylation of imidaclothiz and its
      hydroxylated site, while the oxadiazinane ring in thiamethoxam was not
      hydroxylated or opened. Moreover, the N-methyl group in clothianidin and
      thiamethoxam was not demethylated by S. maltophilia CGMCC 1.1788. The
      biotransformation of imidaclothiz was inhibited by piperonyl butoxide, implying
      that both hydroxylation and dehydrogenation are mediated by a P450 monooxygenase.
      The bioassay results suggested that the activity of 5-hydroxy and olefin
      imidaclothiz was similar but less than that of imidaclothiz against the horsebean
      aphid Aphis craccivora and mosquito larva Culex pipiens, while 5-hydroxy IMT
      showed weak activity against the brown planthopper Nilaparvata lugens.

PMID- 20149645
TI  - Engineering of glycerol utilization pathway for ethanol production by
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae was metabolically engineered to improve ethanol
      production from glycerol. High rates of glycerol utilization were achieved by
      simultaneous overexpression of glycerol dehydrogenase (Gcy) and dihydroxyacetone
      kinase (Dak), which are the enzymes responsible for the conversion of glycerol to
      glycolytic intermediate dihydroxyacetone phosphate. As a result, ethanol
      production in YPH499 (pGcyaDak) was about 2.4-fold higher than wild strain. We
      have also successfully expressed a glycerol uptake protein (Gup1). The overall
      ethanol production in strain YPH499 (pGcyaDak, pGupCas) was 3.4-fold more than in
      wild strain, with about 2.4gL(-1) ethanol produced. These experimental results
      confirmed our metabolic pathway strategies which improve the production of
      ethanol.

PMID- 20149647
TI  - Competitive modeling for the biosorptive removal of copper and lead ions from
      aqueous solution by Mansonia wood sawdust.
AB  - Mansonia wood sawdust is applied as a biosorbent for the removal of copper and
      lead ions from single and binary aqueous solution. The effect of solution pH,
      electrolyte, metal ion competition and temperature were examined to obtain
      insight of its application for industrial waste water treatment. The Langmuir
      isotherm provided a better fit to experimental data for lead ion sorption with a
      higher monolayer capacity, while copper ion sorption was best described by the
      Freundlich and BET isotherms. The combined effect of adsorbing one metal ion in
      the presence of the other metal ion reduced the adsorption capacity of either
      metal ion. In a binary solution, removal of lead ions in the presence of copper
      ions followed the Langmuir isotherm model while the removal of copper ions in
      presence of lead ions followed both the Langmuir and BET isotherm models.

PMID- 20149646
TI  - Biosorption of chromium from aqueous solution and electroplating wastewater using
      mixture of Candida lipolytica and dewatered sewage sludge.
AB  - In this study, the objective was to investigate Cr removal from aqueous
      solutions, as well as Cr, Cu, Ni and Zn from electroplating wastewaters by the
      mixture of Candida lipolytica and sewage sludge. The bioreduction ratios of
      Cr(VI) and the removal ratios of total Cr showed that initial pH, biosorbent
      dosage and contact time were the important parameters for Cr biosorption. The
      range of optimal pH for the mixture (1-5) was wider than C. lipolytica (1-4) and
      sewage sludge (2-4), respectively. Biosorption and bioreduction potentials of
      living C. lipolytica were better than those of cell wall and cytoplasm. Bonded
      hydroxyl group, CH(2) asymmetric stretch, amide I, amide II, amide III, secondary
      amide, pyridine(I)beta(C-H) and pyridine(II)beta(C-H) were detected in the
      biosorbent and they were the functional groups for binding Cr. The effect of Cu
      and Zn in combination was significant on the removal of total Cr and the
      bioreduction of Cr(VI).

PMID- 20149648
TI  - Hydrothermal transformation of Chinese privet seed biomass to gas-phase and semi
      volatile products.
AB  - Hydrothermal (HT) treatment of seeds from Chinese privet (Ligustrum sinense), a
      non-native and invasive species in the southeastern United States, was examined
      with respect to the generation of gas-phase and semi-volatile organic chemicals
      of industrial importance from a lipid-rich biomass resource. Aqueous seed
      slurries were transformed into biphasic liquid systems comprised of a milky
      aqueous phase overlain by a black organic layer. Present in the headspace were
      elevated levels of CO(2) and acetic acid. Analysis of the semi-volatiles by GC-MS
      showed the formation of alkyl substituted benzenes, oxygenated cyclic alkenes,
      phenol, substituted phenolics, and alkyl substituted pyridines. Compared to
      immature seeds, mature seeds gave high relative amounts of oxygenated cyclic
      alkenes (cyclopentenones) and alkyl pyridines. The presence of fatty acids in the
      HT products likely resulted from both lipid hydrolysis reactions and the inherent
      stability of fatty acids under HT treatment conditions. Estimates of lignin and
      protein contents showed no definite trend that could be linked to the HT data.
      The proportion of aromatic HT products appeared to derive primarily from the
      proportion of extractives. Thus, variations in extractives yields impact HT
      product yields and thereby demonstrate the importance of timing in feedstock
      collection to favor targeted HT products.

PMID- 20149649
TI  - Arylpiperazine-containing pyrrole 3-carboxamide derivatives targeting serotonin 5
      HT(2A), 5-HT(2C), and the serotonin transporter as a potential antidepressant.
AB  - Arylpiperzine-containing pyrrole 3-carboxamide derivatives were synthesized and
      evaluated as novel antidepressant compounds. The various analogues were
      efficiently prepared and bio-assayed for binding to 5-HT(2A), 5-HT(2C) receptor,
      and 5-HT transporter. Based on their in vitro and in vivo activities as well as
      selectivity over other neurotransmitter receptors and PK profiles, 33 and 34 were
      identified as lead compounds. Consequently, this pyrrole series of compounds
      appears to be promising enough to warrant further investigation.

PMID- 20149650
TI  - Azabicyclic sulfonamides as potent 11beta-HSD1 inhibitors.
AB  - Inhibition of 11beta-HSD1 has demonstrated potential in the treatment of various
      components of metabolic syndrome. We wish to report herein the discovery of novel
      azabicyclic sulfonamide based 11beta-HSD1 inhibitors. Highly potent compounds
      exhibiting inhibitory activities at both human and mouse 11beta-HSD1 were
      identified. Several compounds demonstrated significant in vivo activity in the
      mouse cortisone challenge assay.

PMID- 20149651
TI  - Discovery of a novel series of potent S1P1 agonists.
AB  - The discovery of a novel series of S1P1 agonists is described. Starting from a
      micromolar HTS positive, iterative optimization gave rise to several single-digit
      nanomolar S1P1 agonists. The compounds were able to induce internalization of the
      S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia
      in mice after oral dosing.

PMID- 20149652
TI  - New anti-malarial phenylpropanoid conjugated iridoids from Morinda morindoides.
AB  - A new phenylpropanoid conjugated iridoid together with four known congeners was
      isolated from Morinda morindoides, used for the therapy of malaria traditionally
      in some African countries, as anti-malarial principles through bioassay-guided
      separation. Furthermore, their absolute stereostructures were unambiguously
      established by a combination of modified Mosher's method and chemical
      correlation.

PMID- 20149654
TI  - The discovery and optimization of hexahydro-2H-pyrano[3,2-c]quinolines (HHPQs) as
      potent and selective inhibitors of the mitotic kinesin-5.
AB  - Here we describe the discovery and optimization of hexahydro-2H-pyrano[3,2
      c]quinolines (HHPQs) as potent and selective inhibitors of the mitotic kinesin-5
      originally found during a high-throughput screening (HTS) campaign sampling our
      in-house compound collection. The compounds optimized subsequently and
      characterized herein were potently inhibiting the ATPase activity of Kinesin-5
      and also exhibited consistent cellular activity, in that cells arrested in
      mitosis and apoptosis induction could be observed. X-ray crystallographic data
      demonstrated that these inhibitors bind in an allosteric pocket of Kinesin-5
      distant from the nucleotide and microtubule binding sites. The selected clinical
      candidate EMD 534085 caused strong growth inhibition in human tumor xenograft
      models using Colo 205 colon carcinoma cells at doses below 30mg/kg administered
      twice weekly without showing severe toxicity as determined by loss of body
      weight.

PMID- 20149653
TI  - C-Aryl glycoside inhibitors of SGLT2: Exploration of sugar modifications
      including C-5 spirocyclization.
AB  - Modifications to the sugar portion of C-aryl glycoside sodium glucose transporter
      2 (SGLT2) inhibitors were explored, including systematic deletion and
      modification of each of the glycoside hydroxyl groups. Based on results showing
      activity to be quite tolerant of structural change at the C-5 position, a series
      of novel C-5 spiro analogues was prepared. Some of these analogues exhibit low
      nanomolar potency versus SGLT2 and promote urinary glucose excretion (UGE) in
      rats. However, due to sub-optimal pharmacokinetic parameters (in particular half
      life), predicted human doses did not meet criteria for further advancement.

PMID- 20149655
TI  - Towards the second generation of Boceprevir: Dithianes as an alternative P2
      substituent for 2,2-dimethyl cycloproyl proline in HCV NS3 protease inhibitors.
AB  - Hepatitis C (HCV) infection is a global health crisis leading to chronic liver
      disease. In our efforts towards a second generation HCV NS3 serine protease
      inhibitor with improved profile, we have undertaken SAR studies in various
      regions of Boceprevir including P2. Herein, we report the synthesis and structure
      activity relationship studies of inhibitors with (S)-1,4-dithia-7
      azaspiro[4.4]nonane-8-carboxylic acid 2 as P2 substituent replacing the
      (1R,2S,5S)-6,6-dimethyl 3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The
      systematic investigation led to the discovery of highly potent inhibitor 25
      (K(i)( *)=7nM, EC(90)=30nM) with improved rat exposure of 2.56microM h.

PMID- 20149656
TI  - Derivatives of aryl amines containing the cytotoxic 1,4-dioxo-2-butenyl
      pharmacophore.
AB  - Several series of compounds containing the 1,4-dioxo-2-butenyl moiety have been
      prepared as candidate cytotoxins, including the methyl N-arylmaleamates, methyl N
      arylfumaramates, and N-arylmaleimides. In addition, the N-arylisomaleimides were
      synthesized which are the structural isomers of N-arylmaleimides. These compounds
      were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine
      L1210 cells. Methyl N-arylfumaramates showed the highest cytotoxic potencies and,
      in particular, methyl N-(3,4-dichlorophenyl)fumaramate is six times more potent
      than melphalan towards L1210 cells and is equipotent with this drug in the Molt
      4/C8 assay. Electrophilicity of compounds under investigation was demonstrated by
      carrying out thiolation using model benzyl mercaptan on representative compounds.
      Methyl N-(3,4-dichlorophenyl)fumaramate and methyl N-(4-chlorophenyl)maleamate
      inhibited human N-myristoyltransferase, a possible molecular target, in high
      micromolar range. QSAR and molecular modeling revealed some correlations between
      different structural features of a number of the molecules and cytotoxic
      potencies. Methyl N-arylfumaramates were well tolerated in mice in comparison to
      the analogs in other series of compounds tested. The data obtained in this
      investigation affords guidelines for preparing new series of molecules with
      greater potencies.

PMID- 20149657
TI  - Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K
      inhibitors.
AB  - Morphing structural features of HTS-derived chemotypes led to the discovery of
      novel 2-cyano-pyrimidine inhibitors of cathepsin K with good pharmacokinetic
      profiles, for example, compound 20 showed high catK potency (IC(50)=4nM), >580
      fold selectivity over catL and catB, and oral bioavailability in the rat of 52%.

PMID- 20149658
TI  - Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with
      antiproliferative activity against melanoma cell lines.
AB  - The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7,
      8, 9 and their antiproliferative activities against A375P human melanoma cell
      line and WM3629 cell line were described. Most compounds showed superior
      antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor.
      Among them, 7a exhibited potent activities on both cell lines (IC(50)=0.62 and
      4.49muM, respectively) and turned out to be a selective and potent CRAF
      inhibitor.

PMID- 20149659
TI  - A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a
      patient with chronic progressive external ophthalmoplegia (CPEO).
AB  - We describe a 62-year-old woman with chronic progressive external ophthalmoplegia
      (CPEO), multiple lipomas, diabetes mellitus, and a novel mitochondrial DNA
      (mtDNA) mutation at nucleotide 4302 (4302A>G) of the tRNA(Ile) gene (MTTI). This
      is the first mutation at position 44 in the variable loop (V loop) of any
      mitochondrial tRNA. The muscle biopsy revealed 10% ragged-red/ragged-blue fibers
      and 25% cytochrome c oxidase (COX)-deficient fibers. No deletions or duplications
      were detected by Southern blot analysis. The 4302A>G transition was present only
      in the patient's muscle and single-fiber analysis revealed significantly higher
      levels of the mutation in COX-deficient than in normal fibers. Like
      tRNA(Leu(UUR)), tRNA(Ile) appears to be a "hot spot" for mtDNA mutations causing
      CPEO.

PMID- 20149660
TI  - Thenar and hypothenar muscle hypertrophy in Becker muscular dystrophy.

PMID- 20149661
TI  - Early onset of cardiomyopathy and primary prevention of sudden death in X-linked
      Emery-Dreifuss muscular dystrophy.
AB  - We report the case of 14-year-old boy with X-linked Emery-Dreifuss muscular
      dystrophy who developed sick sinus syndrome and required placement of an
      implantable intracardiac cardioverter-defibrillator (ICD) to prevent sudden
      death. He demonstrated no significant risk factors for sudden death such as
      depressed left ventricular ejection fraction, or spontaneous or inducible
      ventricular tachycardia. One month after implantation, the patient experienced
      one appropriate ICD discharge.

PMID- 20149662
TI  - Knee proprioception following ACL reconstruction; a prospective trial comparing
      hamstrings with bone-patellar tendon-bone autograft.
AB  - We prospectively studied knee proprioception following ACL reconstruction in 40
      patients (34 men and six women; mean age 31 years). The patients were allocated
      into two equal groups; group A underwent reconstruction using hamstrings
      autograft, and group B underwent reconstruction using bone-patellar tendon-bone
      autograft. Proprioception was assessed in flexion and extension by the joint
      position sense (JPS) at 15 degrees , 45 degrees  and 75 degrees , and time
      threshold to detection of passive motion (TTDPM) at 15 degrees  and 45 degrees ,
      preoperatively and at 3, 6 and 12 months postoperatively. The contralateral
      healthy knee was used as internal control. No statistical difference was found
      between the ACL-operated and the contralateral knees in JPS 15 degrees , 45
      degrees  and 75 degrees  at 6 and 12 months, in both study groups. No statistical
      difference was found between the ACL-operated and the contralateral knees in
      TTDPM 15 degrees  at 6 and 12 months, nor regarding TTDPM 45 degrees  at 3, 6 and
      12 months, in group A. No statistical difference was found in JPS and TTDPM
      between the two grafts, at any time period. Knee proprioception returned to
      normal with ACL reconstruction at 6 months postoperatively, without any
      statistically significant difference between the autografts used.

PMID- 20149663
TI  - Development of selective and reversible pyrazoline based MAO-A inhibitors:
      Synthesis, biological evaluation and docking studies.
AB  - 3,5-Diaryl pyrazolines analogs were synthesized and evaluated for their monoamine
      oxidase (MAO) inhibitory activity. The compounds were found reversible and
      selective towards MAO-A with selectivity index in the magnitude of 10(3)-10(5).
      The docking studies were carried out to gain further structural insights of the
      binding mode and possible interactions with the active site of MAO-A.
      Interestingly, the theoretical (K(i)) values obtained by molecular docking
      studies were in congruence with their experimental (K(i)) values.

PMID- 20149664
TI  - Synthesis, in vitro progesterone receptors affinity of gadolinium containing
      mifepristone conjugates and estimation of binding sites in human breast cancer
      cells.
AB  - Novel gadolinium-based mifepristone conjugates were synthesised using various
      synthetic routes. Moderate antiprogestagenic activity of the new conjugates was
      observed in human breast cancer cells (T47-D cells) using AP (alkaline
      phosphatase) assay. The amount of incorporated Gd determined by inductively
      coupled plasma mass spectroscopy (ICPMS) indicates the number of binding sites
      per cell. These conjugates might be important compounds to develop receptor
      targeted MRI contrast agents as well as other anti-breast cancer therapeutics.

PMID- 20149665
TI  - Design, synthesis, and biological evaluation of novel water-soluble triptolide
      derivatives: Antineoplastic activity against imatinib-resistant CML cells bearing
      T315I mutant Bcr-Abl.
AB  - Imatinib (STI571) is the frontline targeted-therapeutic agent for patients with
      chronic myelogenous leukemia (CML). However, resistance to imatinib due to point
      mutations in Bcr-Abl kinase domain is an emerging problem. We recently reported
      that triptolide (compound 1) could effectively kill CML cells including those
      harboring T315I mutant Bcr-Abl. In the present study, we designed a series of C
      14 triptolide derivatives with C-14-hydroxyl substituted by different amine
      esters (3-18): 3-6 and 13 (by aliphatic chain amine esters); 7-9, 11, 12 and 15
      18 (by alicyclic amine esters with different size), and 10 and 14 (by
      aralkylamine esters).The compounds were examined for their antineoplastic
      activity against CML cells (including KBM5-T315I cells) in terms of proliferation
      inhibition, apoptosis and signal transduction. Nude mouse xenograft model was
      also used to evaluate the in vivo activity. Compounds 2-9, 11-14, 17 and 18
      exhibited a potent inhibitory activity against KBM5 and KBM5-T315I cells. This
      series of derivatives down-regulated Bcr-Abl mRNA. Compounds 4, 5, 8 and 9 were
      further examined for their impact on signaling and apoptosis with immunoblotting.
      Compound 5 was chosen for evaluation in a nude mouse xenograft model. The stereo
      hindrance of C-14 group appeared to be responsible for the antitumor effect. The
      computational small molecule-protein docking analysis illustrated the possible
      interaction between compound 9 and RNA polymerase II. Our results suggest that
      this series of derivatives may be promising agents to overcome imatinib
      resistance caused by the Bcr-Abl-T315I mutation.

PMID- 20149667
TI  - Interaction of (benzylidene-hydrazono)-1,4-dihydropyridines with beta-amyloid,
      acetylcholine, and butyrylcholine esterases.
AB  - Approved drugs for the treatment of Alzheimer's disease belong to the group of
      inhibitors of the acetylcholinesterase (AChE) and NMDA receptor inhibitors.
      However none of the drugs is able to combat or reverse the progression of the
      disease. Thus, the recently reported promising multitarget-directed molecule
      approach was applied here. Using the lead compound DUO3, which was found to be a
      potent inhibitor of the AChE and butyrylcholinesterase (BuChE) as well as an
      inhibitor of the formation of the amyloid (Abeta) plaque, new non-permanently
      positively charged derivatives were synthesized and biologically characterized.
      In contrast to DUO3 the new bisphenyl-substituted pyridinylidene hydrazones 5 are
      appropriate to cross the blood-brain barrier due to their pK(a) values and
      lipophilicity, and to inhibit both the AChE and BuChE. More important some of the
      pyridinylidene hydrazones inhibit the Abeta fibril formation completely and
      destruct the already formed fibrils significantly.

PMID- 20149666
TI  - Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors
      of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles
      in preclinical species.
AB  - Hepatitis is a disease characterized by inflammation of the liver, usually
      producing swelling and, in many cases, permanent damage to liver tissues. Viral
      hepatitis C (HCV), a small (+)-RNA virus, infects chronically 3% of the world's
      population. Boceprevir, SCH 503034, (1) our first generation HCV inhibitor, has
      already established proof-of- concept and is currently in late stage (phase III)
      clinical trials. In view of the positive data from our first generation compound,
      further work aimed at optimizing its overall profile was undertaken. Herein, we
      report that extension of our earlier inhibitor to the P(4) pocket by introducing
      a new sulfonamide moiety and optimization of the P1/P(1)' capping led to the
      discovery of a novel series of inhibitors of the HCV NS3 serine protease.
      Optimization of the P(1) residue significantly improved potency and selectivity.
      The combination of optimal moieties led to the discovery of compound 47 which, in
      addition to being a potent inhibitor of HCV subgenomic RNA replication, was also
      found to have good PK profile in rat, dog and monkey.

PMID- 20149668
TI  - An improved image alignment procedure for high-resolution transmission electron
      microscopy.
AB  - Image alignment is essential for image processing methods such as through-focus
      exit-wavefunction reconstruction and image averaging in high-resolution
      transmission electron microscopy. Relative image displacements exist in any
      experimentally recorded image series due to the specimen drifts and image shifts,
      hence image alignment for correcting the image displacements has to be done prior
      to any further image processing. The image displacement between two successive
      images is determined by the correlation function of the two relatively shifted
      images. Here it is shown that more accurate image alignment can be achieved by
      using an appropriate aperture to filter the high-frequency components of the
      images being aligned, especially for a crystalline specimen with little non
      periodic information. For the image series of crystalline specimens with little
      amorphous, the radius of the filter aperture should be as small as possible, so
      long as it covers the innermost lattice reflections. Testing with an experimental
      through-focus series of Si[110] images, the accuracies of image alignment with
      different correlation functions are compared with respect to the error functions
      in through-focus exit-wavefunction reconstruction based on the maximum-likelihood
      method. Testing with image averaging over noisy experimental images from graphene
      and carbon-nanotube samples, clear and sharp crystal lattice fringes are
      recovered after applying optimal image alignment.

PMID- 20149669
TI  - Symbiotic bacteria and the structural specializations in the ileum of Cephalotes
      ants.
AB  - Light, scanning, and transmission electron microscopy were used to examine the
      ultramorphology and ultrastructure of the ileum of Cephalotes atratus, Cephalotes
      clypeatus, and Cephalotes pusillus. Sections along the ileum revealed differences
      among the three main regions: proximal (or pylorus), medial, and distal. The
      structural specializations present in the ileum of these three ants have
      implications especially to the symbiotic bacteria harbored in this region of the
      digestive tract. The structural similarities are conspicuous for the three
      species examined, suggesting that this is the pattern adopted by the genus
      Cephalotes.

PMID- 20149670
TI  - Differences in mushroom bodies morphogenesis in workers, queens and drones of
      Apis mellifera: neuroblasts proliferation and death.
AB  - Apis mellifera is an interesting model to neurobiological studies. It has a
      relatively small brain that commands the complex learning and memory tasks
      demanded by the social organization. An A. mellifera colony is made up of a
      queen, thousands of workers and a varying number of drones. The latter are males,
      whereas the former are the two female castes. These three phenotypes differ in
      morphology, physiology and behavior, correlated with their respective functions
      in the society. Such differences include the morphology and architecture of their
      brains. To understand the processes generating such polymorphic brains we
      characterized the cell division and cell death dynamics which underlie the
      morphogenesis of the mushroom bodies, through several methods suitable for
      evidence the time and place of occurrence. Cell death was detected in mushroom
      bodies of last larval instar and mainly in black-eyed pupae. Cell division was
      observed in mushroom bodies, primarily at the start of metamorphosis, exhibiting
      temporal differences among workers, queens and males.

PMID- 20149671
TI  - Detection of drugs and explosives using neutron computerized tomography and
      artificial intelligence techniques.
AB  - In this study the development of a methodology to detect illicit drugs and
      plastic explosives is described with the objective of being applied in the realm
      of public security. For this end, non-destructive assay with neutrons was used
      and the technique applied was the real time neutron radiography together with
      computerized tomography. The system is endowed with automatic responses based
      upon the application of an artificial intelligence technique. In previous tests
      using real samples, the system proved capable of identifying 97% of the inspected
      materials.

PMID- 20149672
TI  - Numerical simulation of the PGNA signal from chlorine diffusion gradients in
      concrete.
AB  - A nondestructive test method for detecting chlorides in concrete has been
      developed based on prompt gamma neutron activation (PGNA). Its performance has
      been modeled using a hybrid MCNP/optical ray tracing approach. Since the
      chlorides often come from de-icing salts applied to the concrete surface, the Cl
      concentration has a non-linear depth profile which is typically modeled by the
      erfc function. The signals from this distribution have been simulated for several
      significant Cl capture peaks to estimate the erfc function parameters.

PMID- 20149673
TI  - An optimization of PIXE procedure for high-Z species in a lower Z matrix.
AB  - Singly charged helium ((4)He(+)) induced PIXE technique was used for the
      elemental analysis of tin mining tailings. The procedure gave very good results
      especially when a correction was implemented for X-ray absorption in the low-Z
      region of the spectrum. The use of helium ions to induce X-ray emission was found
      to be adequate, especially in the case of the intermediate light elements
      (12<Z<21) where the nuclear reaction sensitivity decreases. Consequently, helium
      induced X-ray emission analysis can be usefully applied for trace element
      detection of low-Z species in a higher Z matrix as well as high-Z species in a
      lower Z matrix.

PMID- 20149674
TI  - Lung ischaemia-reperfusion induced gene expression.
AB  - OBJECTIVES: Pulmonary dysfunction following lung ischaemia-reperfusion is a well
      known phenomenon, which may contribute to post-cardiac surgical morbidity. The
      process is associated with pulmonary inflammatory response and cellular
      apoptosis. Early molecular mechanisms leading to such lung injury remain largely
      unknown. We examined whether lung ischaemia and reperfusion cause significant
      expression changes in numerous genes in the lungs involved in pulmonary apoptosis
      and other cellular processes by using oligonucleotide microarrays in an
      experimental model of rodent lung ischaemia-reperfusion injury. METHODS: Sprague
      Dawley rodents (n=5 in each group) were anaesthetised and underwent controlled
      ventilation, with varying durations of warm lung ischaemia (60 and 90 min)
      followed by a short reperfusion period. The right middle lobe of the lung was
      harvested. Gene expression changes in the lungs were analysed by rodent DNA
      microarray chips, and reverse transcription polymerase chain reaction (RT-PCR)
      performed to validate changes in gene expression. RESULTS: Significant expression
      changes, with reference to false discovery rate (FDR) controls, were detected in
      over 80 genes following controlled lung ventilation, and more than 50 were up
      regulated more than 2-fold. Lung ischaemia-reperfusion caused expression changes
      in over 50 additional genes, including many novel genes not previously associated
      with lung ischaemia-reperfusion. Up-regulated genes identified include those
      associated with apoptosis, inflammation and cell-cycle control. CONCLUSIONS:
      Large numbers of genes relating to cell metabolism, transcription control,
      inflammation and apoptosis were significantly up- and down-regulated following
      controlled ventilation and early lung ischaemia-reperfusion, consistent with
      previous studies. In addition, novel genes related to lung injury were
      identified. These genetic signatures provide new insights into early molecular
      mechanisms of ischaemia-reperfusion lung injury and help refine therapeutic
      strategies to lessen pulmonary dysfunction following cardiac surgery.

PMID- 20149675
TI  - Study of Pt/TiO2 nanocomposite for cancer-cell treatment.
AB  - The increasing incidence of cancer all over the world demands new, effective and
      secure materials for treatment. In this paper, we propose Pt/TiO(2) nanocomposite
      for cancer-cell treatment because noble metal nanoparticles are supposed to
      enhance the photocatalytic activity of TiO(2) nanoparticles. To evaluate the
      cancer-cell killing effect of our Pt/TiO(2) nanocomposite, TiO(2) and Au/TiO(2)
      nanoparticles are also introduced. The prepared Pt/TiO(2) nanocomposite are
      characterized with transmission electron microscopy (TEM) and UV-vis adsorption
      spectra. Results of cell treatment indicate that Pt/TiO(2) nanocomposite, as
      extremely stable metal-semiconductor nanomaterial, can exhibit a very high
      photodynamic efficiency under a mild ultraviolet radiation. And our Pt/TiO(2)
      nanocomposite shows to be more effective in cancer-cell treatment than TiO(2) and
      Au/TiO(2) nanoparticles. As a result, Pt/TiO(2) nanocomposite may be supposed to
      have a promising application for cancer-cell treatment.

PMID- 20149676
TI  - Absence of 633-nm laser irradiation-induced effects on glucose phosphorylation by
      hexokinase.
AB  - In a paper by Amat et al. (Modification of the intrinsic fluorescence and
      biochemical behavior of adenosine triphosphate ATP after irradiation with visible
      and near-infrared laser light, J. Photochem. Photobiol. B 81 (2005) 26-32) it was
      shown that the conversion of glucose to glucose-6-phosphate by hexokinase in
      vitro was accelerated when ATP, which supplies the reaction with energy, was
      priorly irradiated at non-resonant optical frequencies (NROF, i.e., 655 and 830
      nm). Correspondingly, the authors postulated that NROF may lower the energy
      barrier for the dephosphorylation of ATP's terminal phosphate and thus accelerate
      the reaction rate through a more expeditious energy delivery. Next to the
      established photobiostimulatory influence of visible light on cells, which is
      mediated by cytochrome c oxidase through resonant effects of light, Amat et al.
      posited an interesting theory with which the same processes could be induced
      through non-resonant effects. To investigate the effects of NROF with respect to
      the hexokinase reaction in greater detail, the reaction rates were measured
      spectrofluorometrically after 633-nm laser irradiation of ATP, the ATP-Mg
      complex, hexokinase, and the entire reaction mixture at room temperature (22
      degrees C) and at the optimal reaction temperature (30 degrees C). No differences
      in reaction rates between the NROF-irradiated and control groups were found at
      either temperature. The hypothesis that NROF enhances in vitro hexokinase
      activity by lowering the activation energy for the dephosphorylation of ATP's
      terminal phosphate by hexokinase was therefore disproven. Consequently, it is
      questionable, albeit not unequivocal, that NROF exerts an effect on other ATP
      driven reactions in cell metabolic pathways through a direct impact on ATP.

PMID- 20149678
TI  - Impact of prolactin receptor isoforms on reproduction.
AB  - Prolactin is a hormone involved in growth, development, reproduction, metabolism,
      water and electrolyte balance, brain and behavior, and immunoregulation. Its
      actions on reproductive processes represent the largest group of functions
      identified for this hormone. Besides the classic long form of the prolactin
      receptor, many short form receptors have been identified in rodents and human
      tissues. Mouse mutagenesis studies have offered insight into the biology of the
      prolactin family, providing compelling evidence that different isoforms have
      independent biological activity. The possibility that short forms mediate cell
      proliferation is important for a variety of tissues including mammary glands and
      ovarian follicles. This review summarizes the current knowledge about prolactin
      signaling and its role in reproduction through either long or short isoform
      receptors.

PMID- 20149677
TI  - Pituitary somatostatin receptor signaling.
AB  - Somatotropin-release inhibitory factor (SRIF) is a major regulator of pituitary
      function, mostly inhibiting hormone secretion and to a lesser extent pituitary
      cell growth. Five SRIF receptor subtypes (SSTR1-5) are ubiquitously expressed G
      protein coupled receptors. In the pituitary, SSTR1, 2, 3 and 5 are expressed,
      with SSTR2 and SSTR5 predominating. As new SRIF analogs have recently been
      introduced for treatment of pituitary disease, we evaluate the current knowledge
      of cell-specific pituitary SRIF receptor signaling and highlight areas of future
      research for comprehensive understanding of these mechanisms. Elucidating
      pituitary SRIF receptor signaling enables understanding of pituitary hormone
      secretion and cell growth, and also encourages future therapeutic development for
      pituitary disorders.

PMID- 20149679
TI  - Vitamin D: newly discovered actions require reconsideration of physiologic
      requirements.
AB  - Vitamin D is not just for preventing rickets and osteomalacia. Recent findings in
      animal experiments, epidemiologic studies and clinical trials indicate that
      adequate vitamin D levels are important for cancer prevention, controlling
      hormone levels and regulating the immune response. Although 25 hydroxyvitamin D
      (25OHD) levels >10 ng/ml can prevent rickets and osteomalacia, these levels are
      not sufficient to provide these more recently discovered clinical benefits.
      Rather, levels of 25OHD >30 ng/ml are generally recommended. Determining optimal
      levels of 25OHD and the amount of vitamin D supplementation required to achieve
      those levels for the numerous actions of vitamin D will only be established with
      additional trials. In this review, these newer applications are summarized and
      therapeutic considerations are provided.

PMID- 20149680
TI  - Role of methyl radicals in the growth of PAHs.
AB  - The role of methyl radicals in the networking of sp(2) carbons has been explored
      through kinetic analysis of mass spectra of the gas-phase products of the
      pyrolysis of toluene and toluene/acetone mixtures. Pyrolytic reactions were
      performed in a flow tube reactor at temperatures of 1140-1320 K and a constant
      total pressure of 10.38 Torr with a residence time of 0.585 s. On addition of
      acetone, methyl substituted products and their derivatives were enhanced. Mass
      peaks were observed in several sequences at an interval of 14 mass units; these
      ions correspond to methyl substituted products formed as a result of hydrogen
      abstraction (-H) followed by methyl radical addition (+CH(3)). Each major peak
      was usually preceded by a peak at two mass units lower, which was likely produced
      through dehydrogenation/dehydrocyclization (-H(2)) of methyl substituted
      products. Detected species include a large number of alkyl, cyclotetrafused (CT),
      cyclopentafused (CP) mono-, di-, and polycyclic aromatic hydrocarbons (PAHs)
      along with primary PAHs. The analysis showed that MAC (methyl
      addition/cyclization) has a unique capacity to induce the sequential growth of
      hexagonal networks of sp(2) carbons from all fusing sites of a PAH. Moreover, MAC
      was found capable of answering an important question in PAH growth, which is
      expansion of the CT --> CP --> hexagonal network for which other reported
      mechanisms are inefficient.

PMID- 20149681
TI  - Electrohydrodynamics of charge separation in droplet-based ion sources with time
      varying electrical and mechanical actuation.
AB  - Charge transport and separation in mechanically-driven, droplet-based ion sources
      are investigated using computational analysis and supporting experiments. A first
      principles model of electrohydrodynamics (EHD) and charge migration is formulated
      and implemented using FLUENT CFD software for jet/droplet formation. For
      validation, classical experiments of electrospraying from a thin capillary are
      simulated, specifically, the transient EHD cone-jet formation of a fluid with
      finite electrical conductivity, and the Taylor cone formation in a perfectly
      electrically-conducting fluid. The model is also used to investigate the
      microscopic physics of droplet charging in mechanically-driven droplet-based ion
      sources, such as array of micromachined ultrasonic electrospray (AMUSE). Here,
      AMUSE is subject to DC and AC electric fields of varying amplitude and phase,
      with respect to a time-varying mechanical force driving the droplet formation.
      For the DC-charging case, a linear relationship is demonstrated between the
      charge carried by each droplet and an applied electric field magnitude, in
      agreement with previously reported experiments. For the AC-charging case, a
      judiciously-chosen phase-shift in the time-varying mechanical (driving ejection)
      and electrical (driving charge transport) signals allows for a significantly
      increased amount of charge, of desired polarity, to be pumped into a droplet upon
      ejection. Complementary experimental measurements of electrospray electrical
      current and charge-per-droplet, produced by the AMUSE ion source, are performed
      and support theoretical predictions for both DC- and AC-charging cases. The
      theoretical model and simulation tools provide a versatile and general analytical
      framework for fundamental investigations of coupled electrohydrodynamics and
      charge transport. The model also allows for the exploration of different
      configurations and operating modes to optimize charge separation in atmospheric
      pressure electrohydrodynamic ion sources under static and dynamic electrical and
      mechanical fields.

PMID- 20149682
TI  - Data-dependent neutral gain MS3: toward automated identification of the N-oxide
      functional group in drug metabolites.
AB  - We report here an automated method for the identification of N-oxide functional
      groups in drug metabolites by using the combination of liquid
      chromatography/tandem mass spectrometry (LC/MS(n)) based on ion-molecule
      reactions and collision-activated dissociation (CAD). Data-dependent acquisition,
      which has been readily utilized for metabolite characterization using CAD-based
      methods, is adapted for use with ion-molecule reaction-based tandem mass
      spectrometry by careful choice of select experimental parameters. Two different
      experiments utilizing ion-molecule reactions are demonstrated, data-dependent
      neutral gain MS(3) and data-dependent neutral gain pseudo-MS(3), both of which
      generate functional group selective mass spectral data in a single experiment and
      facilitate increased throughput in structural elucidation of unknown mixture
      components. Initial results have been generated by using an LC/MS(n) method based
      on ion-molecule reactions developed earlier for the identification of the N-oxide
      functional group in pharmaceutical samples, a notoriously difficult functional
      group to identify via CAD alone. Since commercial software and straightforward,
      external instrument modification are used, these experiments are readily
      adaptable to the industrial pharmaceutical laboratory.

PMID- 20149683
TI  - Validation and international regulatory experience for a mycoplasma touchdown PCR
      assay.
AB  - A PCR assay was developed to monitor rFVIII production fermenters for mycoplasma
      contamination. The method uses a simple extraction procedure followed by a
      qualitative "touchdown" (TD) PCR protocol with primers specific to the 16S rRNA
      gene. The method has the capacity to detect a wide range of mycoplasma species.
      Validation was performed according to ICH guidelines and confirmed a limit of
      detection of between 579 and 1715 mycoplasma genome copies spiked per ml of
      sample, and a 1000-10,000-fold greater specificity compared to Gram-positive
      bacteria. In a comparability study, it was comparable in sensitivity to the
      current FDA-recommended broth and agar culture-based method down to one colony
      forming unit (cfu)/ml. The method was validated for its intended use as a
      replacement for culture-based mycoplasma detection during routine fermenter
      monitoring. Regulatory approvals for the method have been obtained in many of the
      major regions and activities are ongoing to address agency concerns regarding the
      comparative limit of detection of the method to culture-based assays.

PMID- 20149684
TI  - Time-line of significant contributions to mycoplasmology.

PMID- 20149685
TI  - Nutritional effects of culture media on mycoplasma cell size and removal by
      filtration.
AB  - Careful media filtration prior to use is an important part of a mycoplasma
      contamination prevention program. This study was conducted to increase our
      knowledge of factors that influence efficient filtration of mycoplasma. The cell
      size of Acholeplasma laidlawii was measured after culture in various nutritional
      conditions using scanning electron microscopy. The maximum cell size changed, but
      the minimum cell size remained virtually unchanged and all tested nutritional
      conditions resulted in a population of cells smaller than 0.2 microm. Culture in
      Tryptic Soy Broth (TSB) resulted in an apparent increase in the percentage of
      very small cells which was not reflected in increased penetration of non
      retentive 0.2 microm rated filters. A. laidlawii cultured in selected media
      formulations was used to challenge 0.2 microm rated filters using mycoplasma
      broth base as the carrier fluid. We used 0.2 microm rated filters as an
      analytical tool because A. laidlawii is known to penetrate 0.2 microm filters and
      the degrees of penetration can be compared. Culture of A. laidlawii in TSB
      resulted in cells that did not penetrate 0.2 microm rated filters to the same
      degree as cells cultured in other media such as mycoplasma broth or in TSB
      supplemented with 10% horse serum.

PMID- 20149686
TI  - Management of blood system in disasters.
AB  - Managing the blood system in disasters is one of the main challenges for any
      blood transfusion service exposed to natural hazards such as earthquakes, floods
      and tsunamis, biological threats such as pandemic influenza as well as manmade
      disruptions and terrorism. Sri Lanka had to face contrasting types of situations.
      The most unexpected and dreadful one was the 2004 December 26 tsunami catastrophe
      which cost >30,000 human lives, leaving more than 23,000 injured. Health services
      were over-burdened with influx of dead bodies and injured people, most due to
      drowning. Injuries varied from small lacerations to deeper wounds, broken arms,
      legs, ribs, damaged organs and head injuries. The National Blood Transfusion
      Service, had to coordinate its blood supply effectively and to manage large
      number of blood donors during the first few days following tsunami. In contrast
      to the acute destruction of tsunami, Sri Lanka also faced a "chronic disaster" of
      3 decades due to the separatist war waged by the Tamil Tigers, until it was
      completely terminated in 2009. There were large scale terrorist attacks using
      suicide bombers, land mines and claymore mines resulting in frequent influxes of
      dead bodies and injured patients to hospitals. The experiences of Sri Lanka blood
      system in the face of two contrasting types of disastrous situations are
      presented.

PMID- 20149687
TI  - Highlights of mycoplasma research--an historical perspective.
AB  - This brief historical development of the biology of the mycoplasmas begins with
      their discovery in 1898 to the present. Mycoplasmas are the smallest free-living
      microorganisms and for years were thought to be viruses because they passed
      through the usual bacterial filters. They lack a cell wall, are widespread in
      nature and many are animal, plant and human pathogens. The extensive use of cell
      cultures in the last fifty years and their frequent contamination with
      mycoplasmas, together with their possession of the smallest genome of any free
      living organism, has drawn enormous attention to these organisms and has revealed
      considerably more about their biology.

PMID- 20149688
TI  - Leiomyoma volume changes at follow-up after uterine artery embolization:
      correlation with the initial leiomyoma volume and location.
AB  - PURPOSE: To study the changes in uterine leiomyoma volume after uterine artery
      embolization (UAE) and to correlate these changes with the initial tumor volume
      and location within the uterus. MATERIALS AND METHODS: The study was performed
      retrospectively on 28 consecutive patients (age, 37-57 years; mean, 48 y +/-
      4.81) with 84 uterine leiomyomas. UAE was performed between June 2006 and August
      2007. All tumors in all patients were evaluated. Magnetic resonance imaging was
      performed before UAE and 3 months and 1 year after UAE. The volume and location
      of each tumor were evaluated in consensus by two radiologists. RESULTS: The mean
      pre-UAE volume of the leiomyomas was 51.6 cm(3) (range, 0.72-371.1 cm(3); SD,
      79.3). Seven tumors were submucous, 28 intramural, and 49 subserous. At 3-month
      follow-up, 83 tumors (98.8%) showed volume reduction (mean, 52.62% +/- 21.85%;
      range, 12.79%-96.67%) and one (1.2%) increased in volume. At 1-year follow-up,
      five tumors (6%) were undetectable, 72 (85.7%) showed a further volume reduction
      of 20.5% +/- 11.92% (range, 2.52%-58.72%) relative to the 3-month volume, and
      seven (8.3%) increased in volume. A statistically significant difference (P =
      .026 at 3 months and P = .0046 at 1 year) in percentage of volume change was
      observed based on tumor location; submucous tumors showed the greatest volume
      reduction and subserous tumors the least reduction. The initial tumor volume
      showed a weak negative correlation (Spearman correlation coefficients, -0.35 at 3
      months and -0.36 at 1 year) with tumor volume change. CONCLUSIONS: UAE results in
      leiomyoma volume reduction at 3-month and 1-year follow-up. The tumor location
      plays an important role in volume changes and the initial tumor volume plays a
      minor role. Further studies with larger numbers of submucous leiomyomas are
      needed.

PMID- 20149689
TI  - Transhepatic assisted transoral placement of a duodenal stent in malignant
      gastric outlet obstruction.
AB  - Gastric outlet obstruction is a well- recognized complication of locally advanced
      carcinoma of the head of the pancreas. The authors report a transoral placement
      of a duodenal stent over a percutaneous guide wire, inserted retrogradely through
      a transhepatic approach via the ampulla of Vater, in a patient in whom
      traditional stent placement was technically not possible. This technique allows
      safe duodenal stent placement for different malignant gastric outlet obstruction
      such as pancreatic, gastric, duodenal, and metastases to the peripancreatic
      region.

PMID- 20149690
TI  - Prospective evaluation of the embolic agent bead block in the treatment of
      uterine leiomyomas with uterine artery embolization: a phase II study.
AB  - PURPOSE: To assess symptom reduction and follow-up magnetic resonance (MR)
      imaging findings in patients who have undergone uterine artery embolization (UAE)
      for symptomatic leiomyomas with the use of Bead Block. MATERIALS AND METHODS:
      Symptomatic patients with uterine leiomyomas were treated with UAE with Bead
      Block. Degree of tumor infarction was assessed 3 months after treatment with
      contrast material-enhanced MR imaging. Each case was categorized as showing less
      than 25% infarction, 25%-89% infarction, or at least 90% infarction. Imaging
      based failure was defined as tumor infarction of less than 90% (12). Symptom and
      quality status were determined by scores from symptom and quality of life (QOL)
      and health-related QOL questionnaires collected 1 and 3 months after
      embolization. RESULTS: This prospective trial enrolled 23 patients. Three-month
      follow-up MR imaging was completed in 22 patients. Tumor necrosis of 90% or
      greater occurred in 10 of 22 patients (45%), and 12 (54%) had partial necrosis of
      25%-89%. The QOL subscale evaluation showed significant reduction of symptom
      severity from baseline to 1 month after treatment (P < .0001), with no
      significant difference between 1 and 3 months of follow-up (P = .42). Because of
      the unacceptably high imaging failure rate of 54%, enrollment was terminated
      before the anticipated 30-patient goal. CONCLUSIONS: The use of Bead Block in the
      manner described resulted in significant clinical improvement. However, there was
      an unacceptably high rate of imaging failure under the existing protocol.
      Modification of the existing protocol should be considered.

PMID- 20149691
TI  - Potential role for coronary computerized angiography for assessing preoperative
      ischemic risk.

PMID- 20149692
TI  - Comparative study of surgical treatment of ulnar nerve compression at the elbow.
AB  - HYPOTHESIS: The optimal surgical treatment for cubital tunnel syndrome remains
      unclear. We aim to evaluate the long-term outcome of surgical treatment by
      comparing the results of the different methods proposed. MATERIALS AND METHODS:
      We retrospectively reviewed 113 patients in whom 3 different surgical methods
      were used for cubital tunnel syndrome treatment. In situ decompression, partial
      epicondylectomy, and anterior subcutaneous transposition were performed from 1997
      to 2007. RESULTS: Results were graded as excellent in 51 patients (45%), good in
      34 (30%), fair in 8 (7%), and poor in 20 (18%). When we compared the results
      among the different surgical procedures, good and excellent results were achieved
      in 26 of 31 patients (84%) treated with in situ decompression, 36 of 45 (80%)
      treated with release and partial medial epicondylectomy, and 23 of 37 (62%)
      treated with release and anterior subcutaneous transposition of the nerve.
      CONCLUSIONS: Our results indicate that in situ decompression and partial
      epicondylectomy both represent efficient and safe methods for cubital tunnel
      syndrome management. In patients in whom anterior subcutaneous transposition was
      performed, although they had a significant improvement of their clinical signs
      and symptoms, they had an inferior outcome when compared with patients treated
      with the other 2 methods.

PMID- 20149693
TI  - Treatment and long term outcome in West syndrome: the clinical reality. A
      multicentre follow up study.
AB  - We systematically reviewed the files of 51 infants presenting with infantile
      spasms and hypsarrhythmia in order to study the initial treatment strategies and
      the long term outcome. 80% of the infants were classified as symptomatic. In the
      nine participating centres, different treatment protocols were used, but the
      large majority of the children received vigabatrin as first line treatment.
      Second line options included hormonal treatment, topiramate and valproate. The
      time to reach cessation of infantile spasms was significantly shorter in the
      cryptogenic group than in the symptomatic group (50% at 13 days versus 66 days
      respectively) and was irrespective of the treatment used. The late follow up data
      (>2 years) showed that 60% of the children had epilepsy and that 75% of the
      children had a delay in their psychomotor development. Again, outcome in the
      cryptogenic group was better than in the symptomatic group, but also in the
      cryptogenic group, 50% of the children had a clear developmental delay, even if
      spasms were controlled early in the course of the disease. Our retrospective
      study illustrates that not only the underlying brain dysfunction is the major
      determinant for later outcome in infantile spasms (symptomatic group) but also
      even a short period of infantile spasms can be responsible for later
      developmental delay (cryptogenic group).

PMID- 20149695
TI  - Dysglycaemia in vascular surgery patients.
AB  - Oral glucose tolerance tests (OGTTs) have detected a pathologic glucose
      metabolism in up to 60% of patients with acute coronary syndromes. Only one-third
      of these were previously diagnosed. The purpose of this study was to determine
      the prevalence of abnormal glucose metabolism among vascular surgery patients.
      METHODS: Between October 2006 and September 2007, 465 consecutive patients
      admitted to the vascular surgery unit were asked to participate in the study;
      however, 121 declined. Among the patients included, 68 had previously known
      diabetes. A total of 276 patients performed an oral glucose tolerance test
      (OGTT). We categorised the findings based on fasting and 2-h plasma glucose
      levels into four groups: diabetes mellitus, impaired glucose tolerance (IGT),
      impaired fasting glucose (IFG) and normal glucose metabolism. Information
      regarding the affected vascular bed and relevant medical history was also
      registered. RESULTS: Of the 276 patients who underwent OGTT, 66 (24%) had IGT, 23
      (8%) had IFG and 33 (12%) had diabetes. As many as 17 of the 33 patients with
      newly diagnosed diabetes would have fulfilled the criteria for diagnosis based
      only on their fasting glucose levels. Including the patients with previously
      known diabetes, the prevalence of dysglycaemia was 55% and that of diabetes 29%.
      CONCLUSIONS: Total prevalence of dysglycaemia in vascular surgery patients
      corresponds well to that of acute coronary syndromes. The prevalence of unknown
      pathological glucose metabolism was 44% in our OGTT material. The use of fasting
      glucose as the sole diagnostic tool for diabetes would have resulted in the
      correct diagnosis in only half of the patients tested. OGTT should be considered
      as a routine investigation in non-diabetic vascular surgery patients. It remains
      to be seen whether early diagnosis and treatment of dysglycaemia in this patient
      group will influence the surgical treatment and outcome.

PMID- 20149694
TI  - Oxidative stress mediates hippocampal neuron death in rats after lithium
      pilocarpine-induced status epilepticus.
AB  - Oxidative stress, which is defined as the over-production of free radicals, can
      dramatically alter neuronal function and has been linked to status epilepticus
      (SE). The pathological process and underlying mechanisms involved in the
      oxidative stress during SE are still not fully clear. In the current study, SE
      was induced in rats by lithium-pilocarpine administration. Our data show that
      hippocampal neuron death occurs at 6h and is sustained for 7 days after SE. The
      production of nitric oxide (NO) started to increase at 30 min and was evident at
      6h and 7 days after SE, which coincided with increased expression of neuronal
      nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and
      malondialdehyde (MDA) after SE, whereas, activated caspase-3 prominently appeared
      at 7 days after SE. Further, FK506, an immunosuppressant, partially rescued the
      neuron death and attenuated the expression of NO, nNOS, iNOS, MDA and activated
      caspase-3. Taken together, our study indicates that oxidative stress mediated
      hippocampal neuron death occurs prior to caspase-3 activation and that FK506
      plays an important role in protecting hippocampal neurons during status
      epilepticus.

PMID- 20149697
TI  - Single-scan 2D NMR correlations by multiple coherence transfers.
AB  - A new scheme for the acquisition of heteronuclear 2D correlations in NMR
      spectroscopy within a single scan, is proposed and demonstrated. The principles
      of this new scheme resemble those of Mansfield's "k-space walk" proposal, in the
      sense that they rely on repetitively transferring spin coherences back-and-forth
      between the two spin systems to be correlated. It is shown that if properly
      executed, these transfers enable the equivalent of a continuous sampling of the
      time-domain space supporting a 2D heteronuclear single-quantum correlation NMR
      spectrum. Details on how to execute the resulting "time-domain walk" experiments
      are given, and examples comparing it against conventional and other single-scan
      2D acquisition alternatives are shown. Advantages, opportunities, and main
      drawbacks of this new ultrafast approach to 2D NMR, are briefly discussed.

PMID- 20149696
TI  - A combination graft of low-molecular-weight silk fibroin with Choukroun platelet
      rich fibrin for rabbit calvarial defect.
AB  - OBJECTIVE: The objective of this study was to determine the capabilities of silk
      fibroin as a biomaterial template for bone formation when mixed with Choukroun
      platelet-rich fibrin (PRF) in vivo. STUDY DESIGN: Ten New Zealand white rabbits
      were used for this study and bilateral round shaped defects were formed in the
      parietal bone (diameter 9.0 mm). The silk fibroin was digested by acid and made
      into powder (molecular weight <1.0 kDa). The right side (experimental group)
      received the silk fibroin plus platelet-rich fibroin and the left side (control
      group) did not receive a graft. Animals were killed at 6 weeks and 12 weeks. The
      specimens were examined by microscopic computerized tomography (micro-CT).
      Subsequently, they underwent decalcification and were stained for histologic
      analysis. RESULTS: There was no significant difference between groups at 6 weeks
      after operation. In the micro-CT results, however, tissue mineral content in the
      experimental group at 12 weeks after operation was 132.09 +/- 4.41 and that in
      the control group was 126.42 +/- 6.62 (P = .011). Tissue mineral density in the
      experimental group was 2,088.88 +/- 648.34, and that in the control group was
      2,029.72 +/- 668.22 (P = .013). The results of the histomorphometric analysis
      were in accordance with the micro-CT results. The total new bone was 49.86 +/-
      7.49% in the control group at 12 weeks after the operation and 59.83 +/- 10.92%
      in the experimental group (P = .021). CONCLUSION: A combined application of
      Choukroun PRF with acid-digested silk fibroin showed more rapid bone healing than
      unfilled control.

PMID- 20149698
TI  - Operation of a 500 MHz high temperature superconducting NMR: towards an NMR
      spectrometer operating beyond 1 GHz.
AB  - We have begun a project to develop an NMR spectrometer that operates at
      frequencies beyond 1 GHz (magnetic field strength in excess of 23.5 T) using a
      high temperature superconductor (HTS) innermost coil. As the first step, we
      developed a 500 MHz NMR with a Bi-2223 HTS innermost coil, which was operated in
      external current mode. The temporal magnetic field change of the NMR magnet after
      the coil charge was dominated by (i) the field fluctuation due to a DC power
      supply and (ii) relaxation in the screening current in the HTS tape conductor;
      effect (i) was stabilized by the 2H field-frequency lock system, while effect
      (ii) decreased with time due to relaxation of the screening current induced in
      the HTS coil and reached 10(-8)(0.01 ppm)/h on the 20th day after the coil
      charge, which was as small as the persistent current mode of the NMR magnet. The
      1D (1)H NMR spectra obtained by the 500 MHz LTS/HTS magnet were nearly equivalent
      to those obtained by the LTS NMR magnet. The 2D-NOESY, 3D-HNCO and 3D-HNCACB
      spectra were achieved for ubiquitin by the 500 MHz LTS/HTS magnet; their quality
      was closely equivalent to that achieved by a conventional LTS NMR. Based on the
      results of numerical simulation, the effects of screening current-induced
      magnetic field changes are predicted to be harmless for the 1.03 GHz NMR magnet
      system.

PMID- 20149699
TI  - In silico designing and optimization of anti-breast cancer antibody mimetic
      oligopeptide targeting HER-2 in women.
AB  - Overexpression of HER-2 is of frequent (20-30%) occurrence in breast cancer.
      Therapeutic targeting of HER-2 with humanized antibody derived oligopeptide may
      be a promising approach to the treatment of breast cancer. HER-2 gene is part of
      a family of genes that play critical roles in regulating transmembrane growth of
      breast cancer cells. Pertuzumab, a recombinant humanized monoclonal antibody
      (2C4), binds to extracellular domain II of the HER-2 receptor and inhibits its
      ability to dimerize with other HER receptors blocking the cell growth, signaling
      and apoptosis induction. The unique binding pocket on HER-2 for pertuzumab
      provides an important target domain for creation of new anticancer drugs. In the
      present work an efficient oligopeptide was designed by our computational method
      that interacts with pertuzumab binding sites of HER-2. In silico docking study
      demonstrated the best specific interaction of RASPADREV oligopeptide with the
      dimerization domain in the HER-2 molecule among various screened oligopeptides.
      ADMET and SAR properties prove the drug likeness of designed oligopeptide as
      having value 0.98.

PMID- 20149700
TI  - Growth hormone receptor d3-variant, insulin-like growth factor binding protein-1 
      575G/A polymorphism and postnatal catch-up growth: association with parameters of
      glucose homeostasis in former extremely low birth weight preterm infants.
AB  - BACKGROUND: Low birth weight predisposes to the development of insulin
      resistance. In addition to auxological parameters such as rapid catch-up growth,
      low IGFBP-1 serum levels in childhood have been linked to an increased risk of
      insulin resistance later in life. Concerning postnatal growth, we previously
      reported the GHRd3-variant to be associated with catch-up growth in preterm
      infants. In children born small for gestational age, a common IGFBP-1 promoter
      polymorphism -575G/A has been linked to IGFBP-1 serum levels and has been
      suggested to be an additional player in the interaction between the IGF-IGFBP
      axis and metabolism. STUDY DESIGN: We analyzed postnatal growth, metabolic
      parameters, and genotypes for the GHRd3-variant and IGFBP-1 -575G/A in 51 former
      extremely low birth weight preterm infants (mean age 5.9 years). RESULTS: GHRd3
      but not IGFBP-1 -575G/A was significantly associated with postnatal growth
      velocity. Catch-up growth, GHRd3, and IFGBP-1 -575G/A did not influence fasting
      insulin or HOMA-IR. However, we found significantly higher HbA1c and lower IGFBP
      1 concentrations in GHRd3-carriers, a finding not seen with respect to IGFBP-1 
      575G/A. Interestingly, HbA1c and IGFBP-1 levels also did not differ between
      children either with or without catch-up growth. CONCLUSIONS: In addition to an
      association with catch-up growth, GHR exon 3 genotype significantly modulates
      HbA1c and IGFBP-1 concentrations in former ELBW infants. In order to confirm this
      observation and to clarify whether the GHRd3-variant might be considered as an
      independent modulator of the low birth weight infant's risk to develop insulin
      resistance later in life, larger studies extending to later ages are required.

PMID- 20149701
TI  - Scanning orientation and polarization effects for XRQA radiochromic film.
AB  - Gafchromic XRQA radiochromic film, is an effective tool for quality assurance and
      dose assessment in kilovoltage radiotherapy and diagnostic applications. Like
      other Gafchromic film products, XRQA film exhibits a variation in dose to
      reflected optical density response with angle of rotation when analysed with a
      light source that is partially or fully polarised such as a desktop scanner.
      Although warnings are not given on manufacturers specifications, this can affect
      dosimetry accuracy and we recommend that it is essential to scan all XRQA films
      in the same orientation. The effect is not as pronounced as EBT Gafchromic film.
      The magnitude of this variation has been measured and shown to be up to 16 +/- 2%
      (1SD) using a fully linear polarised light source was seen with a 90 degrees 
      angle rotation. This would be the maximum variation seen on a desktop scanner
      with a fully polarised light source. For our standard desktop scanner (Epson
      v700) a mean variation of 2 +/- 1% from 0 cGy to 20 cGy applied dose was measured
      as compared to 8 +/- 2% for EBT Gafchromic. We recommend that to decrease
      uncertainty in dose measurement, accurate alignment of the calibration films to
      experimental films be performed on a regular basis. This is especially important
      if your desktop scanner has a high degree of polarization of its light source.

PMID- 20149702
TI  - Gentamycin inhibits the growth of Malassezia pachydermatis in culture.
AB  - BACKGROUND: Malassezia pachydermatis is a yeast of importance in both veterinary
      and human medicine. AIMS: To know if M. pachydermatis grow on mycological media
      with high concentrations of gentamycin. METHODS: Twenty M. pachydermatis strains
      were streaked on Sabouraud Dextrose Agar plates with different concentrations of
      gentamycin. RESULTS: All isolates were inhibited when high concentrations of
      gentamycin were added. CONCLUSIONS: The use of plates with high concentrations of
      gentamycin can lead to some important misdiagnoses: firstly, false-negative
      cultures, and secondly, an erroneous classification of M. pachydermatis as a
      lipid-dependent species. Moreover, all of this could be useful in two therapeutic
      fields: i) in animals, topical gentamycin could be an efficacious treatment for a
      disease such as external otitis in dogs; ii) in humans, we hypothesize that
      gentamycin could be regarded as a possible therapy ("antibiotic-lock") for
      catheter-associated Malassezia spp. infections.

PMID- 20149703
TI  - [Prostate cancer screening and mortality in a European Community trial].

PMID- 20149704
TI  - [Current state of the nursing specialty in surgical medical care].

PMID- 20149705
TI  - Age-related changes in insulin receptor mRNA and protein expression in
      genetically obese Zucker rats.
AB  - AIM: The mechanisms underlying the age-related decrease in insulin-receptor (IR)
      binding in genetically obese Zucker rats are not well understood. For this
      reason, the present study analyzed the expression of IR mRNA and protein in
      selected tissues from 1- to 4-month-old obese (fa/fa) Zucker rats and lean (Fa/-)
      age-matched controls. METHODS: The following parameters were evaluated: (1) IR
      mRNA level, and proportion of isotypes A (exon 11-) and B (exon 11+) of IR mRNA
      in liver, brain and kidney; (2) level, molecular size and tyrosine
      phosphorylation of IR-beta subunit in liver subcellular fractions; and (3)
      stability of liver IR based on sensitivity in vivo of insulin-binding activity
      and IR-beta levels in response to tunicamycin, a glycosylation inhibitor.
      RESULTS: At one month, IR mRNA level was increased in liver and brain, but
      decreased in kidneys and, at four months, both mRNA level and isotype B
      proportion were decreased in liver. From age two months, the following changes in
      liver IR protein expression were observed: (1) decreased IR-beta level in whole
      homogenates, but increased IR-beta levels in endosomal fractions; (2) increased
      IR-beta tyrosine phosphorylation; and (3) at four months, increased levels of
      both intact IR-beta (95 kDa) and IR-beta fragments (72 and 52 kDa) in lysosomal
      fractions, along with decreased stability in vivo of the IR. CONCLUSION: These
      data show that obese Zucker rats display age-related alterations of IR gene
      expression at both pre- and post-translational stages and, in particular,
      increased endocytosis and degradation of IR protein.

PMID- 20149706
TI  - Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients with type 2
      diabetes.
AB  - AIM: This study assessed the impact of regular exercise on inflammatory markers
      (high-sensitivity C-reactive protein [hsCRP], fibrinogen), and matrix
      metalloproteinases (MMPs) and their inhibitors (TIMPs), in patients with type 2
      diabetes mellitus (T2DM). PATIENTS: Fifty overweight patients with T2DM were
      randomly assigned to two groups: (A) an exercise group (EXG, n=25), with self
      controlled exercise for at least 150 min/week and one additional supervised
      exercise session/week; and (B) a control group (COG, n=25), with no exercise
      instructions. All participants were taking oral antidiabetic drugs, and none had
      diabetic complications. Clinical parameters, exercise capacity (VO(2 peak)),
      ventilatory threshold (VT), insulin resistance indices (fasting insulin, HOMA-IR,
      HOMA%S), hsCRP, fibrinogen, MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed at
      baseline and after 16 weeks. RESULTS: No significant changes were found in body
      mass index, waist/hip ratio, insulin-resistance indices, MMP-2 and TIMP-1
      throughout the study in either group (P>0.05). Compared with controls, the EXG
      showed a significant decrease in systolic and mean blood pressure, total and LDL
      cholesterol, and HbA(1c) (P<0.05). Also, exercise significantly suppressed levels
      of fibrinogen (P=0.047), hsCRP (P=0.041) and MMP-9 (P=0.028), and the MMP-9-to
      TIMP-1 ratio (P=0.038), whereas VO(2 peak) (P=0.011), VT (P=0.008) and plasma
      TIMP-2 levels (P=0.022) were considerably upregulated in the EXG vs. COG.
      Standard multiple-regression analyses revealed that MMP-9 changes were
      independently associated with fibrinogen and HbA(1c) changes, while fibrinogen
      changes independently predicted TIMP-2 alterations with exercise. CONCLUSION:
      Mostly self-controlled exercise of moderate intensity ameliorated serum levels of
      pro- and anti-atherogenic markers in patients with T2DM, with no effects on body
      weight. These data offer further insight into the cardioprotective mechanisms of
      exercise in patients with T2DM.

PMID- 20149707
TI  - [The lymph node of Mondor: myth or reality?].
AB  - AIM OF THE STUDY: Lymph node involvement is one of the most significant
      prognostic factors of patients with rectal cancer. Despite major advances in our
      understanding of the propagation of the rectal cancer, the lymphatic drainage of
      the rectum remains unclear. This study was designed to assess the number of lymph
      nodes located around the superior rectal artery and to assess the frequency of
      Mondor's lymph nodes. PATIENTS AND METHODS: Twenty-five anatomic subjects were
      studied. All resections were performed using total mesorectal excision. Lymph
      nodes were sought in the tissue surrounding the superior rectal artery up to 2 cm
      under the ending of the superior rectal artery by manual dissection and were
      submitted for histological examination. The correlation between the number of
      lymph nodes, and the volume and weight of the tissue surrounding the superior
      rectal artery was evaluated by non-parametric Spearman test. RESULTS: The mean
      number of lymph nodes per specimen was 2.7 +/- 1.4. The size of the lymph nodes
      varied between 1 and 7 mm. The lymph nodes were mostly smaller than 3 mm (56%).
      The number of lymph nodes in the superior rectal mesentery was independent of its
      volume and its weight. Seven subjects had a Mondor's lymph node. The mean size of
      Mondor's lymph node was 3.4 +/- 2.1 cm. CONCLUSIONS: The number of NL located
      around the superior rectal artery is small, varying between 1 and 5. The Mondor's
      lymph node is an inconstant rectal NL. Its only characteristic is its location in
      the bifurcation or trifurcation of the superior rectal artery.

PMID- 20149708
TI  - A rare bimuscular conglomeration gluteopiriformis case report.
AB  - The present paper reports a rare anomalous muscle in the gluteal region, which
      appears to be a conglomeration of gluteus maximus and piriformis muscles. The
      muscle was proximally attached to the gluteus maximus and distally merged with
      the piriformis muscle. The innervation of the anomalous muscle was derived from
      the inferior gluteal nerve. Recognition of such a muscle variant may facilitate
      early clinical diagnosis and treatment of patients with symptoms of piriformis
      syndrome or sciatica of unexplained etiology. Contraction of such an anomalous
      muscle could lead to altered biomechanics of the piriformis and the gluteus
      maximus. Such a rare muscle, which morphologically resembles the piriformis and
      developmentally appears to be a part of gluteus maximus could be a challenging
      puzzle for the present day surgeon and radiologist.

PMID- 20149709
TI  - Longitudinal myelitis in a patient with systemic lupus erythematosus.
AB  - Longitudinal myelitis is an exceedingly rare complication of systemic lupus
      erythematosus (SLE), of which only 11 cases have been published so far. We report
      a case in a 65-year-old woman in whom spinal cord dysfunction developed over
      several weeks, resulting in tetraparesis. She had a known history of SLE with a
      circulating anticoagulant. Magnetic resonance imaging of the spine and a
      stereotactic biopsy of a brain lesion established the diagnosis of SLE-related
      longitudinal myelitis. High-dose glucocorticoid therapy had started to bring
      about an improvement when she experienced a series of complications that were
      eventually fatal. Her case is unusual in that longitudinal myelitis is
      exceedingly rare in patients with SLE.

PMID- 20149710
TI  - Extension of an infectious abdominal aneurysm into the L3 and L4 vertebrae:
      report of a difficult case.

PMID- 20149711
TI  - [Treatment of acute scapholunate ligament tears with simple wiring and
      arthroscopic assistance].
AB  - Scapholunate ligament tears give chronic instability leading in SLAC. The wrist
      arthroscopy allows to see the lesions, even in early stage, and to treat them,
      with a simple K-Wires fixation in acute cases. The patients were operated on in
      outpatient basis with tourniquet and local general anaesthesia. In acute cases,
      the scapholunate dissociation was reduced by external and internal manoeuvres.
      The fixation was done with two pins under arthroscopic and fluoroscopic controls.
      We report a series of 66 acute cases (less than 45 days after trauma). Forty-four
      patients were males and 22 females. The average age was 39 years old (range 19
      46). Our average follow-up in acute cases was 36 months (range 14-61). According
      the "Mayo Wrist Score", we obtained 92 % of good or excellent results. The wrist
      arthroscopy is the best technique for early diagnosis, guarantee of best
      functional results.

PMID- 20149712
TI  - Sonochemical synthesis of silver nanorods by reduction of silver nitrate in
      aqueous solution.
AB  - The sonochemical synthesis of silver nanorods has been achieved by ultrasonic
      irradiation of the aqueous solution of silver nitrate, methenamine (HMTA) and
      poly (vinyl pyrrolidone) (PVP) for 60 min. The silver nanorods obtained have
      lengths of 4-7 microm and mean diameters of about 100 nm. The structures of the
      samples were characterized by transmission electron microscopy (TEM), scanning
      electron microscopy (SEM), selected area electron diffraction (SAED) and X-ray
      powder diffraction (XRD), and the chemical composition of the sample was examined
      by energy-dispersive X-ray spectrum (EDS). The effects of the irradiation time,
      the concentration of PVP and the reaction temperature on the morphology of silver
      nanorods were discussed, and the mechanism of the silver nanorods formation was
      tentatively inferred.

PMID- 20149713
TI  - Social inequalities in alcohol consumption in the Czech Republic: a multilevel
      analysis.
AB  - Czech Republic traditionally ranks among the countries with the highest alcohol,
      consumption. This paper examines both risk and protective factors for frequent of
      alcohol, consumption in the Czech population using multilevel analysis. Risk
      factors were measured at the, individual level and at the area level. The
      individual-level data were obtained from a survey for a, sample of 3526
      respondents aged 18-64 years. The area-level data were obtained from the Czech,
      Statistical Office. The group most inclinable to risk alcohol consumption and
      binge drinking are mainly, men, who live as single, with low education and also
      unemployed. Only the variable for divorce rate, showed statistical significance
      at both levels, thus the individual and the aggregated one. No cross-level
      interactions were found to be statistically significant.

PMID- 20149714
TI  - Helix-breaking news: fighting crystalline starch energy deposits in the cell.
AB  - Starch is the major component for providing energy storage for plants. However in
      the cell, starch occurs in semicrystalline granules of various sizes depending on
      the plant species. Therefore, it is important to understand how crystalline
      starch becomes metabolically available. Recent studies provide insight into the
      structural basis of how rare phosphate esters present in starch granules can
      stimulate its degradation in the cell. Phosphorylation at the C-3 position of the
      glucose units seems to play a significant role by inducing strain in crystalline
      starch and resulting in helix unfolding. These findings add a new perspective on
      how plants increase bioavailability of this carbohydrate matrix through a
      phosphate-induced amorphisation mechanism.

PMID- 20149715
TI  - The origins of religion: evolved adaptation or by-product?
AB  - Considerable debate has surrounded the question of the origins and evolution of
      religion. One proposal views religion as an adaptation for cooperation, whereas
      an alternative proposal views religion as a by-product of evolved, non-religious,
      cognitive functions. We critically evaluate each approach, explore the link
      between religion and morality in particular, and argue that recent empirical work
      in moral psychology provides stronger support for the by-product approach.
      Specifically, despite differences in religious background, individuals show no
      difference in the pattern of their moral judgments for unfamiliar moral
      scenarios. These findings suggest that religion evolved from pre-existing
      cognitive functions, but that it may then have been subject to selection,
      creating an adaptively designed system for solving the problem of cooperation.

PMID- 20149716
TI  - Objective clinical performance of 'comfort-enhanced' daily disposable soft
      contact lenses.
AB  - PURPOSE: To examine the objective clinical performance of 'comfort-enhanced'
      daily disposable contact lenses over a 16-h day. METHODS: Four contact lenses
      (Hilafilcon B, Etafilcon A Plus, Nelfilcon A and Nelfilcon A Plus) were evaluated
      in an investigator masked, open label trial at the end of a week's bilateral
      wear. Pre-lens non-invasive tear break-up time (PL-NITBUT), tear prism height,
      bulbar hyperaemia and ocular surface temperature (OST) were measured with the
      lens in situ at 8, 12 and 16h of wear. RESULTS: There was no difference between
      how many hours the lenses types were worn each day (F=0.90, p=0.44). The PL
      NITBUT decreased with the duration of daily lens wear (F=32.0, p<0.001) and was
      more stable with Nelfilcon A Plus (F=6.00, p=0.002) than with the other lenses
      evaluated. Bulbar blood vessels increased in coverage (F=11.5, p<0.001) but not
      overall redness (F=0.0, p=0.99) with the duration of daily lens wear, but there
      was no difference between the lenses (p>0.05). The tear prism height decreased
      with the duration of daily wear (F=27.0, p<0.001) and differed between lenses
      (F=2.9, p=0.04). The OST decreased with the duration of lens wear (F=119.7,
      p<0.001) and was reduced by daily disposable lens wear (F=7.88, p<0.001), but did
      not differ between lenses (F=0.88, p=0.45). CONCLUSIONS: Objective measures of
      tear film indicated a difference between the lenses evaluated for PL-NITBUT and
      tear prism height, but not for wearing time or bulbar conjunctival hyperaemia.
      Therefore clinical benefits of daily disposable 'comfort enhancing' contact
      lenses can be measured, but challenges remain in producing contact lenses that do
      not compromise anterior eye physiology over the whole day.

PMID- 20149717
TI  - Two-component signaling circuit structure and properties.
AB  - Various modeling and experimental studies have analyzed the reactions,
      interconnections, and motifs in two-component systems, with an eye toward
      understanding their physiological implications and the differences between
      alternative designs. Examples where recent progress has been made include aspects
      of autoregulation, signal integration in branched pathways, cross-talk
      suppression, and cross-regulation via connector proteins.

PMID- 20149719
TI  - Microbial enhanced oil recovery (MEOR).
AB  - Two-thirds of the oil ever found is still in the ground even after primary and
      secondary production. Microbial enhanced oil recovery (MEOR) is one of the
      tertiary methods purported to increase oil recovery. Since 1946 more than 400
      patents on MEOR have been issued, but none has gained acceptance by the oil
      industry. Most of the literature on MEOR is from laboratory experiments or from
      field trials of insufficient duration or that lack convincing proof of the
      process. Several authors have made recommendations required to establish MEOR as
      a viable method to enhance oil recovery, and until these tests are performed,
      MEOR will remain an unproven concept rather than a highly desirable reality.

PMID- 20149720
TI  - Nanobiotechnology--quo vadis?

PMID- 20149718
TI  - Use of two-component signal transduction systems in the construction of synthetic
      genetic networks.
AB  - Two-component signal transduction systems are a common type of signaling system
      in prokaryotes; the typical cell has dozens of systems regulating aspects of
      physiology and controlling responses to environmental conditions. In this review,
      I consider how these systems may be useful for engineering novel cell functions.
      Examples of successful incorporation of two-component systems into engineered
      systems are noted, and features of the systems that favor or hinder potential
      future use of these signaling systems for synthetic biology applications are
      discussed. The focus will be on the engineering of novel couplings of sensory
      functions to signaling outputs. Recent successes in this area are noted, such as
      the development of light-sensitive transmitter proteins and chemotactic receptors
      responsive to nitrate.

PMID- 20149721
TI  - A spectroscopic and computational study of Al(III) complexes in sodium cryolite
      melts: ionic composition in a wide range of cryolite ratios.
AB  - The structure of sodium cryolite melts was studied using Raman spectroscopy and
      quantum chemical calculations performed at the density functional theory level.
      The existence of bridged forms in the melts was argued first from the analysis of
      experimental Raman spectra. In the quantum chemical modelling emphasis was put on
      the construction of potential energy surfaces describing the
      formation/dissociation of certain complex species. Effects of the ionic
      environment were found to play a crucial role in the energetics of model
      processes. The structure of the simplest possible polymeric forms involving two
      Al centres linked through F atoms ("dimers") was thoroughly investigated. The
      calculated equilibrium constants and model Raman spectra yield additional
      evidence in favour of the dimers. This agrees with a self-consistent analysis of
      a series of Raman spectra for a wide range of the melt composition.

PMID- 20149722
TI  - Functionality test for drug safety alerting in computerized physician order entry
      systems.
AB  - PURPOSE: To evaluate the functionality of drug safety alerting in hospital
      computerized physician order entry (CPOE) systems by a newly developed
      comprehensive test. METHODS: Comparative evaluation of drug safety alerting
      quality in 6 different CPOEs used in Dutch hospitals, by means of 29 test items
      for sensitivity and 19 for specificity in offices of CPOE system vendors.
      Sensitivity and specificity were calculated for the complete test, and for the
      categories "within-order checks", "patient-specific checks", and "checks related
      to laboratory data and new patient conditions". Qualitative interviews with 16
      hospital pharmacists evaluating missing functionality and corresponding pharmacy
      checks. RESULTS: Sensitivity ranged from 0.38 to 0.79 and specificity from 0.11
      to 0.84. The systems achieved the same ranking for sensitivity as for
      specificity. Within-order checks and patient-specific checks were present in all
      systems; alert generation or suppression due to laboratory data and new patient
      conditions was largely absent. Hospital pharmacists unanimously rated checks on
      contra-indications (absent in 2 CPOEs) and dose regimens less than once a day
      (absent in 4 CPOEs) as important. Pharmacists' opinions were more divergent for
      other test items. A variety of pharmacy checks were used, and clinical rules
      developed, to address missing functionality. CONCLUSIONS: Our test revealed
      widely varying functionality and appeared to be highly discriminative. Basic
      clinical decision support was partly absent in two CPOEs. Hospital pharmacists
      did not rate all test items as important and tried to accommodate the lacking
      functionality by performing additional checks and developing clinical rules.

PMID- 20149723
TI  - Human adenoviruses in respiratory infections: sequencing of the hexon
      hypervariable region reveals high sequence variability.
AB  - BACKGROUND: In respiratory infections, human adenoviruses (hAdV) of species B1
      and C are frequently detected, but severe or even fatal disease outbreaks are
      predominantly caused by only few serotypes. The molecular typing of hAdV hexon
      sequences can help to speed up the discrimination of serotypes, thus improving on
      time epidemiological examinations and patient care. OBJECTIVES: We aimed to
      develop a molecular method for the rapid species B1 and C serotype identification
      in respiratory samples based on sequence generation of the hexon hypervariable
      region (HVR). STUDY DESIGN: We developed two PCR-based genotyping systems for a
      generic HVR amplification and sequence determination of species B1 and C viruses.
      The assays were applied to hAdV prototypes and 106 samples. RESULTS: The primer
      sets proved to be capable of amplifying all B1 and C serotypes. The viruses
      detected in clinical samples belong to serotypes 1, 2, 3, 5 and 6. The obtained
      sequences of serotypes 2, 3 and 5 form 2-3 phylogenetic clusters that are based
      on the characteristic amino acid changes within the variable HVR sites.
      CONCLUSIONS: Our assay can significantly speed up the time-span needed for
      serotype identification and will improve epidemiological surveillance and patient
      care. The obtained hexon sequences of field viruses vary significantly and form
      multiple genetic lineages. The variability is focussed on the HVR sites and can
      be interpreted as the ongoing evolutionary process. Further research is needed on
      the hexon sequence variability of other (respiratory) hAdV serotypes.

PMID- 20149724
TI  - The effectiveness of routine laboratory findings in determining disease severity
      in patients with Crimean-Congo hemorrhagic fever: severity prediction criteria.
AB  - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease
      caused by a tick-borne virus from the Bunyaviridae family. OBJECTIVES: To
      determine the predictive criteria for severity among patients with CCHF based on
      clinical and laboratory findings. STUDY DESIGN: This retrospective study was
      conducted on patients with CCHF and hospitalized between June 2004 and August
      2008 at Karadeniz Technical University, Turkey. Demographic characteristics,
      clinical findings and laboratory tests on admission of all patients with CCHF
      were investigated. RESULTS: A total of 152 patients with confirmed CCHF were
      investigated. Sixty-three (41.4%) of these patients were in the severe group.
      Laboratory findings using the ROC curve method and optimum diagnostic cut-off
      points for specific laboratory parameters in the severe group were; PLT: 90,000,
      Hb: 13.5 g/dL, PT: 13.1s, aPTT: 34 s, INR: 1, AST: 117U/L, ALT: 71U/L, AST/ALT:
      1.62, LDH: 508 U/L, CK: 267 U/L and CRP: 0.59 mg/dL. At multivariable analysis,
      the risk for a severe clinical course in CCHF patients increased 2.59 and 3.93
      times in the presence of platelet count and Hb below cut-off values, whereas the
      same risk increased 2.95, 2.92 and 3.47 times when the results for INR, AST and
      CRP, respectively, were above the predetermined cut-off values. CONCLUSIONS: A
      number of laboratory findings that can easily be measured at routine examination
      of patients hospitalized with a suspicion of CCHF are valuable and sensitive
      predictors. These parameters will contribute considerably to the design, practice
      and management of supportive treatment, blood and blood products replacement and
      intensive care services.

PMID- 20149725
TI  - High-frequency transcutaneous electrical nerve stimulation (TENS) differentially
      modulates sensorimotor cortices: an MEG study.
AB  - OBJECTIVE: Transcutaneous electrical nerve stimulation (TENS) affects
      excitability of the central motor system as well as the somatosensory system. To
      determine whether TENS has influence on excitability in the sensorimotor cortices
      of TENS-treated finger muscle, we investigated magnetoencephalogram associated
      with voluntary, self-paced finger movement before and after TENS. METHODS: High
      frequency TENS was applied on the extensor digitorum muscle for 15 min. Subjects
      underwent alternate middle finger and thumb extension movements before and after
      the TENS. We recorded movement-related cortical magnetic field (MRCF) associated
      with TENS-treated middle finger movement and that from untreated thumb movement.
      RESULTS: The current source for motor field (MF) was located in the pre-central
      motor cortex and anteriorly-oriented, and that for motor evoked field one (MEF1)
      was found in the post-central somatosensory cortex and posteriorly-oriented. The
      amplitude of MF for TENS-treated middle finger movement decreased but unchanged
      for untreated thumb movement after TENS. The amplitude of MEF1 decreased for
      either finger movement after TENS. CONCLUSION: High-frequency TENS to the forearm
      muscle modulates excitability of the limited area of motor cortex but wider area
      of primary somatosensory cortex. SIGNIFICANCE: High-frequency TENS to the forearm
      muscle modulates excitability of the primary somatosensory cortex and motor
      cortex in a different manner.

PMID- 20149726
TI  - Altered eyeblink reflex conditioning in restless legs syndrome patients.
AB  - BACKGROUND: Restless legs syndrome (RLS) is characterized by abnormal leg
      sensations and an uncontrollable urge to move the lower extremities during rest
      periods. Evidence suggests that reflex tasks that involve sensory-motor
      integration may be altered in RLS patients. This led us to determine if RLS
      patients show alterations in a sensory-motor reflex conditioning task called
      differential eyeblink conditioning. METHODS: RLS subjects were washed out of
      treatment medication for 7 days prior to testing. Subjects (20 RLS and 19
      Control) received 120 discrimination conditioning trials consisting of 60 CS+
      trials (i.e., an auditory stimulus paired with the airpuff-US separated by a
      silent 900 ms trace interval) and 60 CS- trials (i.e., a different auditory
      stimulus that was NOT paired with the US). RESULTS: Control subjects showed
      normal differential responding to the CS+ and CS-, but the RLS patients showed
      little or no differential responding. A post-test questionnaire provides evidence
      that symptomatic interference was not responsible for the eyeblink conditioning
      deficits in the RLS subjects, and further suggests that neurophysiological
      factors were responsible for these deficits. CONCLUSIONS: Together these results
      suggest that deficits in eyeblink conditioning are related to the pathophysiology
      of RLS. The eyeblink conditioning test may also be useful for supporting a
      clinical diagnosis or treatment strategy for RLS.

PMID- 20149727
TI  - Emerging clinical role of strain imaging in echocardiography.
AB  - Myocardial strain is a measure of tissue deformation and strain rate is the rate
      at which deformation occurs. When applied to the heart, strain and strain rate
      give fundamental information on myocardial properties and mechanics that would
      otherwise be unavailable. Site specificity and angle independency are two unique
      characteristics of strain and strain rate data. Strain and strain rate can be
      obtained with tissue Doppler imaging or with 2D speck tracking. These two
      techniques derive information on strain and strain rate in two fundamentally
      different ways and each has its own advantages and limitations. Tissue Doppler
      imaging yields velocity information from which strain and strain rate are
      mathematically derived whereas 2D speckle tracking yields strain information from
      which strain rate and velocity data are derived. Data obtained from these two
      different techniques may not be equivalent due to limitations inherent with each
      technique. Strain and strain rate imaging have been used to assess myocardial
      function in a wide range of cardiac conditions. They are useful in detecting
      early left ventricular (LV) dysfunction in the setting of systemic diseases with
      cardiac involvement, in differentiating transmural from non-transmural
      infarction, and in identifying LV contractile reserve in regurgitant valve
      lesions. When used with dobutamine echocardiography, strain and strain rate
      imaging can identify viable myocardium and aid the detection of myocardial
      ischaemia. Strain and strain rate imaging can also be used to assess right
      ventricular and left atrial function. Despite significant promises, strain and
      strain rate imaging is technically challenging and signal to noise ratio may be
      potentially affected by a wide range of factors. As a result, strain and strain
      rate imaging have been slow to get incorporated into everyday clinical practice.
      Ongoing research and further technical development are likely to improve the
      quality of the data and the more general acceptance of these new modalities of
      imaging in echocardiography.

PMID- 20149728
TI  - The value of dual-source 64-slice CT coronary angiography in the assessment of
      patients presenting to an acute chest pain service.
AB  - BACKGROUND: The absence of radiological evidence of plaque on computed
      tomographic coronary angiography (CTCA) reliably excludes obstructive coronary
      artery disease. METHODS: We studied patients who presented to our emergency
      department with chest pain and were admitted to our chest pain assessment
      service. If they were free of pain and without high-risk features of myocardial
      ischaemia including elevation of serum biomarkers they underwent CTCA and
      performed a standard treadmill exercise test. RESULTS: Eighty-nine patients aged
      56.3+/-8.6 years were admitted. Eleven of them had selective angiography; CTCA
      identified all who had obstructive disease. More than half of the 85 patients who
      had normal values of cardiac troponin and of the 75 with a negative exercise test
      had radiological evidence of disease. During follow-up for 355+/-72 days none
      died, suffered myocardial infarction or required coronary artery surgery: two
      with obstructive disease underwent percutaneous coronary intervention 1 and 7
      days after the index study. CONCLUSIONS: The CTCA findings were significantly
      correlated with those of selective angiography and with troponin status and
      increased the ascertainment of coronary artery disease in a cohort of patients at
      low risk for clinically significant ischaemic heart disease.

PMID- 20149729
TI  - Nuclear imaging in the evaluation of clinical restorative cardiac therapies.
AB  - Gene- and cell-based therapeutic procedures have entered the cardiovascular
      field. Many of these novel interventions aim at cardiac regeneration and the
      initial experimental groundwork has been promising. But early clinical experience
      did not always confirm the experimental findings and it is felt that the full
      potential of cardiac gene and cell therapy has, by far, not been exploited.
      Conflicting clinical results emphasise the need for powerful non-invasive tools
      to monitor the success of therapy and identify most suitable candidates. As
      reviewed here, established clinical cardiac imaging tools, together with novel
      molecular-targeted approaches, are expected to advance the field of myocardial
      regeneration and to expedite progress and clinical translation.

PMID- 20149730
TI  - On reducing cardiovascular disease to a rarity: clinical strategies and their
      cost-effectiveness.

PMID- 20149731
TI  - Descending necrotising mediastinitis, a fatal disease to keep in mind.
AB  - Descending necrotising mediastinitis, a term used by Estrera (1983) [1], is a
      rare and serious disease requiring prompt diagnosis and immediate aggressive
      surgical therapy. It should be considered in the differential diagnosis of acute
      mediastinal widening. We report an unusual case of primary retropharyngeal
      abscess complicated by descending necrotising mediastinitis and bilateral empyema
      in a 56-year-old diabetic man. The diagnosis of descending necrotising
      mediastinitis (DNM) was established by the characteristic findings on computed
      tomography. The patient was treated by cervicotomy and staged bilateral
      posterolateral thoracotomy.

PMID- 20149732
TI  - The use of coronary revascularisation procedures in urban Australian Aboriginals
      and a matched general population coronary procedures in Aboriginals.
AB  - BACKGROUND: Coronary revascularisation procedures may be under-used for
      Aboriginal Australians with ischaemic heart disease (IHD). We compared the use of
      procedures in an urban Aboriginal population and a non-Aboriginal external
      comparison group. METHODS: The Perth Aboriginal Atherosclerosis Risk (PAARS)
      cohort (n=998) and 3695 age- and sex-matched non-Aboriginals were electronically
      linked to Western Australian hospital morbidity data to identify admissions and
      revascularisation procedures between 1980 and 2006. RESULTS: There were 731
      admissions for IHD for 983 PAARS participants with hospital admissions and 391 in
      3150 non-Aboriginals. There were 136 first procedures overall; 43% of Aboriginals
      having a procedure were women versus 18.5% of non-Aboriginals. 41% of Aboriginal
      patients and 48% of non-Aboriginals had procedures (p=0.12). Aboriginals were
      more likely to have coronary artery bypass grafts (CABG) (40.5%) than a
      percutaneous coronary intervention (PCI), compared to the general population
      (23%, p=0.02). The proportion of first procedures for acute coronary syndrome
      (ACS) admissions was 61% for both groups, 80% and 85%, respectively, being PCI.
      CONCLUSIONS: Coronary revascularisation procedures for IHD were used with equal
      frequency in Aboriginal people and matched non-Aboriginals. Aboriginal people
      were more likely to have CABG than PCI. Revascularisation rate and type in ACS
      admissions were the same.

PMID- 20149734
TI  - The quality of life of family caregivers of cancer patients in the east of
      Turkey.
AB  - PURPOSE: In this study, the aim was to examine the quality of life of family
      caregivers of cancer patients in the east of Turkey. METHOD: The study design was
      descriptive. Data were collected by the researcher in Oncology-Hematology
      policlinic and Chemotherapy unit of Yakutiye Research Hospital of Ataturk
      University. Participants were 18 years old and older. The sample included 106
      family caregivers who were living in the same flat with the patients during
      caregiving. Data were collected using a questionnaire that included
      sociodemographic questions for family caregivers and the World Health
      Organization Quality of Life-Short Form, Turkish Version (WHOQOL-BREF TR).
      RESULTS: The mean domain scores of WHOQOL-BREF(TR) were 70.12 (SD=19.24) for
      social, 68.26 (SD=20.10) for physical, 59.70 (SD=18.07) for psychological, 56.32
      (SD=15.12) for national environment, and 53.87 (SD=16.99) for environment
      domains. About 71.7% of caregivers shared the caregiving process with someone
      else. Environmental domain scores of those who shared the caregiving process with
      someone else were higher. The environment domain scores of men (49.6, SD=17.1)
      were lower than those of women. As the income lowers, lowered, so did the quality
      of life score in every domain. The quality of life scores of those feeling
      unhealthy during the last two weeks were low in every domain. CONCLUSION:
      Physical and psychological health of family caregivers in assisted living
      facilities should be comprehensively supported by professionals.

PMID- 20149733
TI  - Quality of life, symptom experience and distress of lung cancer patients
      undergoing chemotherapy.
AB  - The diagnosis of lung cancer in the advanced stage of illness, the poor prognosis
      associated with the disease, and the side effects of chemotherapy all have an
      impact on various dimensions of quality of life (QoL). THE PURPOSE OF THE
      RESEARCH: The current study was designed to describe the QoL and symptom distress
      of lung cancer patients undergoing chemotherapy and to explore the relationships
      between demographic/treatment-related characteristics and QoL. METHODS AND
      SAMPLE: The sample consisted of 154 lung cancer patients undergoing chemotherapy.
      The symptom experiences and QoL of lung cancer patients undergoing chemotherapy
      were evaluated using the Memorial Symptom Assessment Scale and Quality of Life
      Index - Cancer Version. RESULTS: The lung cancer patients had low QoL scores. The
      scores on the Health and Functioning subscale were the lowest (20.33 +/- 5.59),
      while those of the Family subscale were the highest (27.66 +/- 2.77). The most
      common physical symptoms experienced by lung cancer patients were lack of energy,
      coughing, pain, lack of appetite, and nausea, while the psychological symptoms
      were feeling nervous, difficulty sleeping, feeling sad, and worrying. There was a
      negative relationship between the symptom distress and quality of life scores (r=
      0.45; p<0.000). Females and those with low income levels and performance status
      experienced greater symptom distress. CONCLUSIONS: Lung cancer patients receiving
      chemotherapy suffer many limitations due to the symptoms and disruptions to their
      QoL, arising from both the disease process and its treatment. Lung cancer
      patients need to be assessed regularly and supported.

PMID- 20149735
TI  - Keeping courage during stem cell transplantation: a qualitative research.
AB  - PURPOSE: The purpose of this qualitative study was to explore how patients
      undergoing stem cell transplantation (SCT) keep courage and pull through this
      demanding therapy. METHOD: A qualitative design using a grounded theory approach
      was used. Data were collected by participant observation and by conducting 16
      semi-structured interviews with patients who had undergone SCT and six interviews
      with nurses. RESULTS: Research findings provide an explanation for the process of
      keeping courage during SCT. In this publication we focus on the core category in
      that process: the writing of a positive story. To endure and give meaning to the
      suffering of the therapy, patients do their best to believe in a happy ending.
      Patients exert every effort to keep faith: they count their blessings, they
      protect their positive story from the assaults of negative information and
      threatening signals through rationalization and they do everything in their power
      to increase their chances of a happy ending. The positive story is most
      vulnerable during aplasia, when patients seem to lose both physical and mental
      strength. Patients feel nurses and doctors help them to muster up courage. Nurses
      carry patients through the hardest and most despondent moments. CONCLUSIONS:
      During stem cell transplantation, patients make many efforts in order to write a
      positive story and to keep courage. These efforts involve much more active
      strategies than the rather passive concept of hope suggests.

PMID- 20149736
TI  - Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2
      study.
AB  - BACKGROUND: Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour
      with low metastatic potential and is associated with substantial skeletal
      morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear
      (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast
      activation. We investigated the potential therapeutic effect of denosumab, a
      fully human monoclonal antibody against RANKL, on tumour-cell survival and growth
      in patients with GCT. METHODS: In this open-label, single-group study, 37
      patients with recurrent or unresectable GCT were enrolled and received
      subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days
      8 and 15 of month 1. The primary endpoint was tumour response, defined as
      elimination of at least 90% of giant cells or no radiological progression of the
      target lesion up to week 25. Study recruitment is closed; patient treatment and
      follow-up are ongoing. The study is registered with Clinical Trials.gov,
      NCT00396279. FINDINGS: Two patients had insufficient histology or radiology data
      for efficacy assessment. 30 of 35 (86%; 95% CI 70-95) of evaluable patients had a
      tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by
      radiology. Adverse events were reported in 33 of 37 patients; the most common
      being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five
      patients had grade 3-5 adverse events, only one of which (grade 3 increase in
      human chorionic gonadotropin concentration not related to pregnancy) was deemed
      to be possibly treatment related. Five serious adverse events were reported
      although none were deemed treatment related. INTERPRETATION: Further
      investigation of denosumab as a therapy for GCT is warranted. FUNDING: Amgen,
      Inc.

PMID- 20149737
TI  - Denosumab: a breakthrough in treatment of giant-cell tumour of bone?

PMID- 20149738
TI  - Defining pelvic-radiation disease for the survivorship era.

PMID- 20149740
TI  - SIRT1 - a metabolic sensor that controls blood vessel growth.
AB  - Blood vessels deliver nutrients and oxygen to cells and tissues in the body. When
      blood supply is insufficient new vessels form to meet the metabolic tissue
      requirements. Several studies have examined the cellular and molecular principles
      of blood vessel formation, yet little is known about how vessels sense and
      integrate environmental signals originating from nutrient- and oxygen-deprived
      tissues to achieve functional vascular patterning. The NAD(+)-dependent
      deacetylase SIRT1 mediates adaptation to environmental stresses by adjusting
      cellular responses to the energetic state of the cell and recent studies
      highlight important functions of SIRT1 in regulating vascular growth, shape, and
      function. Here, we review the emerging role of SIRT1 as a metabolic sensor
      coupling energy and oxygen homeostasis to the growth and function of the
      vasculature.

PMID- 20149739
TI  - Isoform specific functions of Nox protein-derived reactive oxygen species in the
      vasculature.
AB  - The family of NADPH oxidases consists of seven members that are all producing
      reactive oxygen species (ROS). In the cardiovascular systems three NADPH oxidases
      are expressed: Nox1, Nox2 and Nox4, which all exhibit different physiological
      functions such as regulating blood pressure, mediating growth factor signaling
      and controlling cell proliferation. In this article the recent research
      concerning the specificity and function mediated by NADPH oxidases will be
      reviewed.

PMID- 20149741
TI  - Lessons from the inflammasome: a molecular sentry linking Candida and Crohn's
      disease.
AB  - Candida albicans is a diploid fungus that colonizes the gastrointestinal tract
      asymptomatically in a large proportion of the human population, but can cause
      life-threatening conditions in immunocompromised patients. Recent immunological
      investigations have revealed the Nod-like receptor pyrin domain-containing
      protein 3 (NLRP3) to be a cytosolic surveillance mechanism against germinating
      Candida. These observations point to the idea of a molecular link between Candida
      and a spectrum of auto-inflammatory diseases. When excessive activation of NLRP3
      occurs, it can confer resistance against disseminating Candida infection but
      might also cause NLRP3-associated periodic syndromes. Alternatively, we propose a
      pathophysiological model whereby a defective NLRP3-coupled inflammasome can
      result in enhanced mucosal colonization of granuloma-provoking microorganisms,
      including C. albicans, precipitating the formation of Crohn's disease-associated
      inflammatory lesions.

PMID- 20149743
TI  - Exploring a regulatory role for mast cells: 'MCregs'?
AB  - Regulatory cells can mould the fate of the immune response by direct suppression
      of specific subsets of effector cells, or by redirecting effectors against
      invading pathogens and infected or neoplastic cells. These functions have been
      classically, although not exclusively, ascribed to different subsets of T cells.
      Recently, mast cells have been shown to regulate physiological and pathological
      immune responses, and thus to act at the interface between innate and adaptive
      immunity assuming different functions and behaviors at discrete stages of the
      immune response. Here, we focus on these poorly defined, and sometimes apparently
      conflicting, functions of mast cells.

PMID- 20149744
TI  - Cohen's Conjecture, Howard's Hypothesis, and Ptashne's Ptruth: an exploration of
      the relationship between affinity and specificity.
AB  - Both affinity and specificity for ligands directly influence the functions of
      biological macromolecules. Some investigators assume that there is a consistent
      relationship between the affinity of a receptor molecule for its cognate
      ligand(s) and the specificity of that same receptor (affinity for cognate versus
      non-cognate ligands). However, analysis of the range of physical factors that
      account for changes in affinity, in any particular direction and to any
      particular degree, of a receptor for a cognate ligand suggests strongly that such
      factors can have disparate effects on the affinities of the receptor for
      different non-cognate ligands. Therefore, there can be no simple relationship
      between affinity and specificity as defined by relative binding of the receptor
      to cognate and non-cognate ligands.

PMID- 20149745
TI  - Good cells gone bad: the cellular origins of cancer.
AB  - One issue in human cancer research that remains largely unresolved is the
      identity of the normal cell type in which tumorigenesis begins. Knowledge of the
      starting cell populations targeted by transforming events is crucial for
      characterizing early neoplastic changes and understanding how normal cellular
      processes become disrupted during cancer development. Recent focus on cancer stem
      cells (CSCs) has been accompanied by the frequent assumption that these cells
      derive from normal stem cells. However, evidence from mouse tumor models has
      demonstrated that cancer can also arise from committed progenitors. This review
      highlights recent insights gained from studies of the normal cell populations
      targeted for malignant transformation - in other words, the cellular origins of
      cancer.

PMID- 20149746
TI  - An exploration of student nurses' thoughts and experiences of using a video
      recording to assess their performance of cardiopulmonary resuscitation (CPR)
      during a mock objective structured clinical examination (OSCE).
AB  - Cardiopulmonary resuscitation (CPR) is an essential skill taught within
      undergraduate nursing programmes. At the author's institution, students must pass
      the CPR objective structured clinical examination (OSCE) before progressing to
      second year. However, some students have difficulties developing competence in
      CPR and evidence suggests that resuscitation skills may only be retained for
      several months. This has implications for practice as nurses are required to be
      competent in CPR. Therefore, further opportunities for students to develop these
      skills are necessary. An action research project was conducted with six students
      who were assessed by an examiner at a video-recorded mock OSCE. Students self
      assessed their skills using the video and a checklist. Semi-structured interviews
      were conducted to compare checklist scores, and explore students' thoughts and
      experiences of the OSCE. The findings indicate that students may need to repeat
      this exercise by comparing their previous and current performances to develop
      both their self-assessment and CPR skills. Although there were some differences
      between the examiner's and student's checklist scores, all students reported the
      benefits of participating in this project, e.g. discussion and identification of
      knowledge and skills deficits, thus emphasising the benefits of formative
      assessments to prepare students for summative assessments and ultimately clinical
      practice.

PMID- 20149747
TI  - Effects of race/ethnicity on triple CGG counts in the FMR1 gene in infertile
      women and egg donors.
AB  - This cross-sectional cohort study investigated 385 females (344 infertile women
      and 41 oocyte donors), the numbers of CGG repeats on the FMR1 gene and
      differences between races/ethnicities. Traditional definitions of
      neuropsychiatric risks are classified as common, intermediate, premutation and
      full mutation ranges. Normal CGG count range was here, however, defined by box
      and whisker plot as 26-32 repeats (median 30). Distribution of abnormal outliers
      in CGG counts from this normal range was then compared between women of
      Caucasian, African and Asian descent. African and Asian women demonstrated a
      higher prevalence of two normal count alleles (65%) than Caucasians (54.3%;
      P=0.03). Caucasians demonstrated the highest rate of allele abnormalities (43.3%)
      and were the only race/ethnicity also demonstrating abnormalities in both FMR1
      alleles. Asian women demonstrated significantly fewer low outlier counts than
      Caucasians (P=0.002) and Africans (P=0.03). This study, thus, suggests
      significant racial/ethnic differences in triple CGG counts on the FMR1 gene
      between races/ethnicities. Since CGG counts on FMR1 are associated with ovarian
      reserve, these findings may reflect potential differences between
      races/ethnicities in ovarian function and female fertility reported in the
      literature.

PMID- 20149748
TI  - Lymphoma--emerging realities in sub-Saharan Africa.
AB  - Substantial geographical differences exist for Hodgkin and other
      lymphoproliferative disorders with these having previously been documented in a
      report from the lymphoma reclassification project. In the light of rampant human
      immunodeficiency syndrome, largely centred in sub-Sahara, this experience is
      updated in a further 512 consecutive individuals treated over an 8-year period in
      a privately based academic centre. Median age was 55.2 years 61% were males, 10%
      had Hodgkin lymphoma and, overall, constitutional symptoms were present in 20%.
      Prior to referral 19% had received chemotherapy and a further 20% some form of
      irradiation. Median survival in hairy cell leukaemia (n=14), chronic lymphocytic
      leukaemia-small lymphocytic lymphoma (n=103), Hodgkin (n=41) and follicular
      lymphoma (n=59) was not reached at the time of analysis and exceeded 36 months.
      This was followed by 32 months for those with mantle cell (n=7), splenic (n=2)
      and extranodal marginal cell (n=11), 24 months for T-cell lymphomas (n=24), 20
      months for diffuse large B-cell variants (n=88) but only 12 months for the
      aggressive tumours exemplified by Burkitt (n=7) and lymphoblastic subtypes (n=6).
      The remaining 36 patients had to be excluded because numbers were too small for
      statistical analysis or unreliable staging. Adverse factors were constitutional
      symptoms, prior treatment with chemotherapy, intermediate or high-risk scores as
      defined by the international prognostic index, histologic grading and certain
      anatomical sites of primary tumour. In contrast gender, staging by Rye or Rai
      classification, retroviral infection and prior treatment with radiotherapy were
      without effect. Overall survival at 3 years in each category was compared to the
      curve for the entire cohort and was 100% in hairy cell leukaemia receiving two
      chlorodeoxyadenosine and greater than 88% in Hodgkin lymphoma treated according
      to the German study group protocols (p=0.0004). Corresponding figures for chronic
      lymphocytic leukaemia-small lymphocytic lymphoma were 82% (p=0.0006), follicular
      lymphoma 71% (p=0.060), peripheral T-cell lymphoma 43% (p=0.0156), diffuse large
      B-cell lymphoma 39% (p<0.0001), aggressive tumours 25% (p=0.0002) and for the
      indolent categories including mantle cell, splenic and extra nodal marginal cell
      lymphomas 22% (p=0.2023). Outcome argues in favour of patient management by a
      multidisciplinary team implicit in which are standardised protocols for
      diagnosis, staging and treatment. Under these circumstances the well recognized
      centre effect applies when results approximate those from first world reference
      centres. Conversely any deviation from such a disciplined approach is unlikely to
      achieve comparable benefit and therefore to be strongly discouraged.

PMID- 20149749
TI  - Renal pseudoaneurysm following laser lithotripsy: endovascular treatment of a
      rare complication.
AB  - Hemorrhagic complications of renal transplantation can be life threatening and
      require prompt and timely intervention. This brief report describes the
      exceedingly rare formation of an extrarenal pseudoaneurysm of a transplant renal
      artery following laser lithotripsy for nephrolithiasis in a teenage male. The
      pseudoaneurysm ruptured into the renal collecting system. Transarterial coil
      embolization of the wide-neck saccular pseudoaneurysm of the extraparenchymal
      renal artery with the assistance of a 'safety microguidewire' was successfully
      performed and the allograft was preserved.

PMID- 20149750
TI  - Association of angiotensin converting enzyme and angiotensin type 2 receptor gene
      polymorphisms with renal damage in posterior urethral valves.
AB  - OBJECTIVE: To examine the association with renal damage in patients with
      posterior urethral valves (PUV) of two renin-angiotensin system gene
      polymorphisms: angiotensin converting enzyme insertion/deletion (ACE I/D) and
      angiotensin type 2 receptor (AT2R A1332G), PATIENTS AND METHODS: In 120 patients
      with PUV, after stabilization, transurethral fulguration or a Blocksom
      vesicostomy was performed. Records were reviewed for age at diagnosis,
      biochemical renal function at diagnosis, results of urine cultures, voiding
      cystourethrograms, radiologic, sonographic and nuclear medicine scan findings,
      and follow-up data. ACE I/D genotypes were determined by the polymerase chain
      reaction using allele specific primers. RESULTS: The frequency of the ACE DD
      genotype was significantly higher in patients with chronic kidney disease
      (P=0.02) and renal scarring (P=0.05). These genotypes were also associated with a
      statistically higher incidence of vesicoureteral reflux, diurnal incontinence,
      proteinuria and hypertension. A significantly higher frequency of the AT2R GG
      genotype was found in PUV patients as compared to healthy unrelated control
      subjects (P=0.001), and in PUV patients with scarring (P=0.02). CONCLUSION: The
      ACE DD and AT2R GG genotypes are associated with chronic kidney disease and
      scarring in PUV patients. The GG genotype incidence is higher among PUV patients
      compared to the control population, and further studies in this area may help
      understanding of the genetic basis of PUV.

PMID- 20149751
TI  - Non-neurogenic elimination disorders in children.
AB  - Non-neurogenic elimination disorders cover a wide spectrum of lower urinary tract
      and bowel dysfunctions, observed in the absence of a neurological background or
      lower urinary tract malformation. We reviewed conditions responsible for
      incontinence during bladder filling with normal voiding patterns (such as
      overactive bladder, giggle incontinence, post-void dribbling), and dysfunctional
      voiding syndromes. Dysfunctional elimination syndrome usually includes detrusor
      sphincter dyscoordination, small-capacity overactive bladder or decompensated
      large poorly contractile bladder, and large-volume post-micturition residuals,
      occasionally associated with bowel dysfunction. At the most severe end of the
      spectrum lies the non-neurogenic neurogenic bladder syndrome, characterized by
      the association of a severe impairment of the upper urinary tract with a
      dysfunctional elimination syndrome. It must be emphasized that if the term 'non
      neurogenic' relates to the absence of a neurological lesion, it is however
      conceivable that these conditions actually do have an underlying neurological
      cause that remains to be identified.

PMID- 20149752
TI  - Food safety education using an interactive multimedia kiosk in a WIC setting:
      correlates of client satisfaction and practical issues.
AB  - OBJECTIVE: To assess acceptability of food safety education delivered by
      interactive multimedia (IMM) in a Supplemental Nutrition Program for Women,
      Infants and Children Program (WIC) clinic. METHODS: Female clients or caregivers
      (n=176) completed the food-handling survey; then an IMM food safety education
      program on a computer kiosk. Satisfaction with program, participant demographics,
      and change in food-handling behavior were assessed by univariate analyses.
      RESULTS: Over 90% of the participants enjoyed the kiosk, and most (87.5%)
      reported using computers a lot. Compared with participants with education beyond
      high school, participants with less education were more likely to report enjoying
      the kiosk (98.2% vs 88.1%, P = .007), preferred learning with the kiosk (91.7% vs
      79.1%, P = .02), and would like to learn about other topics using IMM (95.4% vs
      86.6%, P = .04). CONCLUSIONS AND IMPLICATIONS: Food safety education delivered by
      IMM was well accepted by inner-city WIC clinic clients, including those with less
      education.

PMID- 20149753
TI  - Good's syndrome remains a mystery after 55 years: A systematic review of the
      scientific evidence.
AB  - Good syndrome (GS) is a rare association of thymoma and immunodeficiency first
      described more than 50 years ago. However, this syndrome still remains a mystery
      to clinicians. We systematically reviewed all the clinical, laboratory and
      immunologic findings from 152 patients with Good syndrome. The syndrome has a
      worldwide distribution and approximately half of the cases (47%) have been
      described in Europe. The diagnosis of thymoma preceded the diagnosis of
      hypogammaglobulinemia, infection, or diarrhea in 42% of patients whereas in 38%
      of patients the diagnoses were made almost simultaneously within 2 months of each
      other. We found significant mortality in patients with this syndrome (44.5%).
      Astute clinical acumen and increased awareness about the clinical and
      immunological profile of this syndrome may increase early recognition of this
      syndrome and prevent mortality. Further studies are needed to elucidate this
      clinical entity.

PMID- 20149754
TI  - Epilepsy duration impacts on brain glucose metabolism in temporal lobe epilepsy:
      results of voxel-based mapping.
AB  - OBJECTIVE: [(18)F]Fluorodeoxyglucose positron emission tomography ([(18)F]FDG
      PET) is a valuable method for detecting focal brain dysfunction associated with
      epilepsy. Evidence suggests that a progressive decrease in [(18)F]FDG uptake
      occurs in the epileptogenic cortex with an increase in the duration of epilepsy.
      In this study, our aim was to use statistical parametric mapping (SPM) to test
      the validity of this relationship in a retrospective study of patients with
      temporal lobe epilepsy (TLE). METHODS: [(18)F]FDG-PET scans of 46 adult patients
      with pharmacoresistant unilateral TLE (25 RTLE and 21 LTLE) were subjected to SPM
      analysis. RESULTS: Forty-six patients were diagnosed with nonlesional TLE, 16 of
      whom had hippocampal sclerosis (HS). The average duration of epilepsy was 17.4 +/
      12.3 years (3-46 years), <5 years in 10 patients and >or=10 years in 30
      patients. Visual analysis of [(18)F]FDG-PET scans revealed hypometabolism in the
      epileptogenic temporal cortex in 31 (67%) patients. After SPM analysis of all
      [(18)F]FDG-PET images, hypometabolism was unilateral and reported in lateral and
      mesial structures of the epileptogenic temporal cortex in addition to the
      ipsilateral fusiform and middle occipital gyrus. Subsequent analysis revealed
      that temporal lobe hypometabolism was present only in patients with longer
      epilepsy duration (>or=10 years) in parahippocampal gyrus, uncus, and middle and
      superior temporal gyrus (P < 0.05 corrected). Epilepsy duration was inversely
      correlated with decreased glucose uptake in the inferior temporal gyrus,
      hippocampus, and parahippocampal gyrus of the epileptogenic temporal cortex (P <
      0.05). Age at seizure onset did not affect the correlation between epilepsy
      duration and glucose uptake except in the inferior temporal gyrus (P < 0.05).
      CONCLUSION: Voxel-based mapping supports the assertion that glucose
      hypometabolism of the epileptogenic temporal lobe cortex and other neighboring
      cortical regions increases with longer epilepsy duration in TLE.

PMID- 20149755
TI  - Language and brain volumes in children with epilepsy.
AB  - In this study the relationship between language skill and frontotemporal volumes
      was compared in 69 medically treated subjects with epilepsy and 34 healthy
      children, aged 6.1-16.6 years. Also, whether patients with linguistic deficits
      had abnormal volumes and atypical associations between volumes and language
      skills in these brain regions was determined. The children underwent language
      testing and MRI scans at 1.5 T. Brain tissue was segmented and frontotemporal
      volumes were computed. Higher mean language scores were significantly associated
      with larger inferior frontal gyrus, temporal lobe, and posterior superior
      temporal gyrus gray matter volumes in the epilepsy group and in the children with
      epilepsy with average language scores. Increased total brain and dorsolateral
      prefrontal gray and white matter volumes, however, were associated with higher
      language scores in the healthy controls. Within the epilepsy group, linguistic
      deficits were related to smaller anterior superior temporal gyrus gray matter
      volumes and there was a negative association between language scores and
      dorsolateral prefrontal gray matter volumes. These findings demonstrate abnormal
      development of language-related brain regions, and imply differential
      reorganization of brain regions subserving language in children with epilepsy
      with normal linguistic skills and in those with impaired language.

PMID- 20149756
TI  - Antiepileptic drugs and quality of life in the elderly: results from a randomized
      double-blind trial of carbamazepine and lamotrigine in patients with onset of
      epilepsy in old age.
AB  - During an international double-blind trial evaluating the efficacy and
      tolerability of lamotrigine and carbamazepine in patients aged >or=65 with newly
      diagnosed epilepsy, the comparative effects of the drugs on health-related
      quality of life were investigated based on screening and 12-, 28-, and 40-week
      data, using the modified Side Effect and Life Satisfaction (SEALS) Inventory and
      the Liverpool Adverse Event Profile. Of 167 patients, 29 discontinued before
      first follow-up, and data were incomplete for 13. In 125 eligible subjects (62
      taking carbamazepine, 63 taking lamotrigine), comparable baseline data did not
      change significantly during medication, within or across treatments. A borderline
      difference in the SEALS Dysphoria subscores favored lamotrigine. No difference
      between completers and noncompleters was identified. Twelve-week data for
      noncompleters were comparable across treatments. Changes in the inventories up to
      40 weeks correlated moderately. Neither lamotrigine nor carbamazepine seems
      likely to cause significant changes in health-related quality of life measures
      after 40 weeks at therapeutic doses.

PMID- 20149757
TI  - Clinical features of psychogenic nonepileptic seizures: a study of 64 cases in
      southwest China.
AB  - This article describes the clinical features of psychogenic nonepileptic seizures
      (PNES) in people in southwest China. Patients with a confirmed diagnosis of pure
      PNES by video/EEG monitoring were retrospectively reviewed. A total of 64
      patients with PNES were included, 32 (50%) of whom were male. Twenty (31.3%)
      patients had previously been misdiagnosed and treated for epilepsy. Psychological
      trauma and head injuries were considered antecedent traumatic factors. A history
      of abuse was rare. The PNES cases were divided into three subtypes: psychogenic
      minor motor seizures, psychogenic major motor seizures, and unresponsive
      seizures. Age at onset was identified as a predictor of prognosis. The results of
      this study demonstrated a higher prevalence of PNES in males compared with
      previous studies. The semiology of PNES in China is similar to that in Western
      countries. Classification of semiology may be helpful in the differential
      diagnosis of PNES.

PMID- 20149758
TI  - Prostate gland edema after single-fraction high-dose rate brachytherapy before
      external beam radiation therapy.
AB  - PURPOSE: High-dose rate brachytherapy (HDRB) is frequently used as a boost to
      external beam radiation therapy (EBRT) in prostate cancer patients. With the
      increasing use of small planning target volume margins in EBRT, prostatic edema
      induced by HDRB can be a contributing factor to geometric miss when HDRB is
      performed before or during EBRT. We assessed prostate gland volumetric change
      after single-fraction HDRB and its impact on definition of treatment volume for
      EBRT. METHODS AND MATERIALS: Thirty-one consecutive patients with intermediate
      risk prostate cancer treated with single-fraction HDRB (10 Gy) combined with
      hypofractionated EBRT were analyzed. A second CT scan was performed 7 days after
      HDRB, and images were coregistered with the planning CT scan that contained the
      original clinical target volume (CTV). The post-HDRB prostate CTV volume was
      compared with the original CTV by a single observer. RESULTS: All patients
      presented volumetric variation. In most cases (68%), the prostate increased in
      volume, whereas it decreased in 32%. The mean prostatic volume was 42.2 cc before
      HDRB and 43.6 cc after HDRB, representing a mean volume difference of 3.4%,
      ranging from -14.2% to 23.8% (p=0.756). This difference is the result of mean
      changes of 0.6mm (-6.1 to 6.6) in the anterior-posterior, 0.5mm (-5.5 to 3.0) in
      the lateral, and 0.2mm (-5.0 to 5.0) in the superior-inferior axes. CONCLUSIONS:
      Although a nonsignificant volumetric change occurs after single-fraction HDRB,
      individual variations on specific axis could lead to important uncertainties
      during EBRT.

PMID- 20149759
TI  - Investigation of geometric distortions on magnetic resonance and cone beam
      computed tomography images used for planning and verification of high-dose rate
      brachytherapy cervical cancer treatment.
AB  - PURPOSE: To measure the amount of geometric distortions present in the three
      dimensional imaging modalities--cone beam computed tomography (CBCT) and magnetic
      resonance imaging (MRI)--used at University of California, San Francisco, CA, for
      gynecologic high dose rate brachytherapy. METHODS AND MATERIALS: An MRI- and CT
      compatible water phantom with two different sets of support structures was
      designed and built for this study. The support structures were used to precisely
      position catheters that were filled with either an MRI contrast agent or a string
      of radio-opaque markers. The first support structure without anatomy was built to
      test system-based distortions. A second structure included two types of
      gynecologic applicators as well as several anatomical structures, including bones
      and rectum to test object-induced distortions. Images were acquired with CT (for
      reference), kilovoltage CBCT, and MRI (1.5 T with T1- and T2-weighted images).
      The difference in catheter positions between the images and the CT images was
      analyzed. RESULTS: For CBCT, the mean of the absolute deviations was below 1mm in
      all directions. The inherent uncertainty in the measurement of distortion was
      less than 0.5mm. MRI presented mean absolute system-based distortions between 0.6
      and 1.1mm in the central region of the image and between 0.7 and 2.3mm in the
      outer region. Images with the applicator and anatomy in place created mean
      absolute distortions of 0.4, 0.8, and 0.8mm or less for CBCT, MR-T1, and MR-T2
      images, respectively. CONCLUSIONS: The distortions measured in the presence of
      applicators are small enough to validate the use of CBCT and 1.5 T MRI for GYN
      brachytherapy treatment planning and verification.

PMID- 20149760
TI  - Image integration to guide ablation of incessant left atrial appendage
      tachycardia.

PMID- 20149761
TI  - Identification and quantitative determination of a major circulating metabolite
      of gambogic acid in human.
AB  - Gambogic acid (GA), a promising anticancer candidate, is a polyprenylated
      xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi. The
      major circulating metabolite of GA in human, 10-hydroxygambogic acid (10-OHGA),
      was identified by comparison of the retention time and mass spectra with those of
      reference standard using liquid chromatography-tandem mass spectrometry. The
      reference standard of 10-OHGA was isolated from bile samples of rats after
      intravenous injection of GA injection, and its structure was confirmed by NMR.
      Then, a selective and sensitive method was developed for the quantitative
      determination of this metabolite in human plasma. After liquid-liquid extraction
      by ethyl acetate, the analyte and the internal standard were separated on a Sepax
      HPC18 column (100 mm x 2.1 mm i.d., 3.0 microm) with a mobile phase of 10mM
      ammonium acetate water solution containing 0.1% formic acid-acetonitrile (20:80,
      v/v). The detection was performed on a single quadrupole mass spectrometer
      equipped with electrospray ionization (ESI) source. The calibration curve was
      linear over the range of 3-2000 ng/mL for 10-OHGA. The developed quantification
      method can now be used for the pharmacokinetic and pharmacological studies of 10
      OHGA after intravenous infusion of GA injection in human.

PMID- 20149762
TI  - Simultaneous determination of glucuronic acid and sulfuric acid conjugated
      metabolites of daidzein and genistein in human plasma by high-performance liquid
      chromatography.
AB  - Isoflavone aglycones daidzein (Dein) and genistein (Gein) are mainly present as
      glucuronides and sulfates in human plasma, and small amounts of the intact
      aglycones are also detected. In the present study, we have developed a high
      performance liquid chromatography (HPLC)-UV-diode-array detector (DAD) method for
      the determination of intact 16 metabolites of Dein and Gein in plasma, especially
      focusing on highly polar conjugated metabolites at both 4' and 7 positions on the
      isoflavone ring with glucuronic acid and/or sulfuric acid (7-glucuronide-4'
      sulfates and 4',7-diglucuronides). Luteolin-3',7-di-O-glucoside was used as an
      internal standard. Solid-phase extraction was performed on an Oasis HLB cartridge
      (60 mg, 3 cm(3)) with a recovery of >ca. 80%. The HPLC assay was performed on a
      Hydrosphere C18 column (100 mm x 4.6 mm I.D., particle size 3 microm). The mobile
      phase consisted of a mixture of 10 mM ammonium acetate solution and acetonitrile
      run under gradient mode at a flow rate of 1.5 ml/min. The UV detection wavelength
      was set at 250 nm. For UV spectral analysis, the diode-array detection wavelength
      was set at 220-360 nm. All HPLC analyses were performed at 45 degrees C. Each
      calibration for the determination of 16 metabolites gave a linear signal
      (r>0.997) over a concentration range of 5-5000 ng/ml. The lower limits of
      quantification of these metabolites were 21.1-23.4 ng/ml and the lower limits of
      detection were 7.9-9.4 ng/ml. This method was used in a preliminary experiment to
      determine the plasma concentration of intact 16 metabolites after oral
      administration of kinako (baked soybean powder) to a healthy volunteer. The
      present HPLC-UV-DAD method should be useful for the metabolic and pharmacokinetic
      investigations of isoflavones in humans.

PMID- 20149763
TI  - Determination of aldehydes in exhaled breath of patients with lung cancer by
      means of on-fiber-derivatisation SPME-GC/MS.
AB  - A number of volatile organic compounds (VOCs) have been identified and used in
      preliminary clinical studies of the early diagnosis of lung cancer. The aim of
      this study was to evaluate the potential of aldehydes (known biomarkers of
      oxidative stress) in the diagnosis of patients with non-small cell lung cancer
      (NSCLC). We used an on-fiber-derivatisation SPME sampling technique coupled with
      GC/MS analysis to measure straight aldehydes C3-C9 in exhaled breath. Linearity
      was established over two orders of magnitude (range: 3.3-333.3*10(-12) M); the
      LOD and LOQ of all the aldehydes were respectively 1*10(-12) M and 3*10(-12) M.
      Accuracy was within 93% and precision calculated as % RSD was 7.2-15.1%. Aldehyde
      stability in a Bio-VOC((r)) tube stored at +4 degrees C was 10-17 h, but this
      became >10 days using a specific fiber storage device. Finally, exhaled aldehydes
      were measured in 38 asymptomatic non-smokers (controls) and 40 NSCLC patients.
      The levels of all of the aldehydes were increased in the NSCLC patients without
      any significant effect of smoking habits and little effect of age. The good
      discriminant power of the aldehyde pattern (90%) was confirmed by multivariate
      analysis. These results show that straight aldehydes may be promising biomarkers
      associated with NSCLC, and increase the sensitivity and specificity of previously
      identified VOC patterns.

PMID- 20149764
TI  - Determination and identification of estrogenic compounds generated with
      biosynthetic enzymes using hyphenated screening assays, high resolution mass
      spectrometry and off-line NMR.
AB  - This paper describes the determination and identification of active and inactive
      estrogenic compounds produced by biosynthetic methods. A hyphenated screening
      assay towards the human estrogen receptor ligand binding domain (hER)alpha and
      hERbeta integrating target-ligand interactions and liquid chromatography-high
      resolution mass spectrometry was used. With this approach, information on both
      biologic activity and structure identity of compounds produced by bacterial
      mutants of cytochrome P450s was obtained in parallel. Initial structure
      identification was achieved by high resolution MS/MS, while for full structure
      determination, P450 incubations were scaled up and the produced entities were
      purified using preparative liquid chromatography with automated fraction
      collection. NMR spectroscopy was performed on all fractions for 3D structure
      analysis; this included 1D-(1)H, 2D-COSY, 2D-NOESY, and (1)H-(13)C-HSQC
      experiments. This multidimensional screening approach enabled the detection of
      low abundant biotransformation products which were not suitable for detection in
      either one of its single components. In total, the analytical scale biosynthesis
      produced over 85 compounds from 6 different starting templates. Inter- and intra
      day variation of the biochemical signals in the dual receptor affinity detection
      system was less than 5%. The multi-target screening approach combined with full
      structure characterization based on high resolution MS(/MS) and NMR spectroscopy
      demonstrated in this paper can generally be applied to e.g. metabolism studies
      and compound-library screening.

PMID- 20149765
TI  - Liquid chromatography-tandem mass spectrometry for the determination of low
      molecular mass aldehydes in human urine.
AB  - A simple and sensitive method is proposed for the determination of seven low
      molecular mass aldehydes in human urine samples using liquid chromatography with
      tandem mass spectrometric detection. Urine samples diluted twofold with 0.3M
      hydrochloric acid are aspirated into a LiChrolut EN solid-phase extraction column
      impregnated with 2,4-dinitrophenylhydrazine for cleanup, derivatization and
      preconcentration of the aldehydes. After elution of the hydrazones with
      acetonitrile, an aliquot is injected directly into the chromatograph.
      Identification and quantification of aldehydes was performed with electrospray in
      negative ion mode by selected reaction monitoring. By using synthetic urine
      samples, linearity is established over the concentration range 0.1-30 microg/l
      and limits of detection from 15 to 65 ng/l. The intra- and inter-day precision
      (RSD, %) of the aldehydes ranged from 2.9% to 6.4% and 3.6% to 9.3%,
      respectively, and specific uncertainties were ca. 5.0+/-0.3 ng for all aldehydes.
      Average recoveries performed on two levels by enriching synthetic urine samples
      ranged between 92% and 100%. The method was also validated in terms of study
      sample stability including long-term and short-term analyte stability, freeze
      thaw and extract stability. In summary, the method proposed surpasses other
      recent chromatographic alternatives in terms of the limit of detection and sample
      requirements for analysis.

PMID- 20149766
TI  - Determination of cymipristone in human plasma by liquid chromatography
      electrospray ionization-tandem mass spectrometry.
AB  - A rapid, specific and sensitive liquid chromatography-electrospray ionization
      tandem mass spectrometry method was developed and validated for determination of
      cymipristone in human plasma. Mifepristone was used as the internal standard
      (IS). Plasma samples were deproteinized using methanol. The compounds were
      separated on a ZORBAX SB C(18) column (50 mm x 2.1 mm i.d., dp 1.8 microm) with
      gradient elution at a flow-rate of 0.3 ml/min. The mobile phase consisted of 10
      mM ammonium acetate and acetonitrile. The detection was performed on a triple
      quadruple tandem mass spectrometer by selective reaction monitoring (SRM) mode
      via electrospray ionization. Target ions were monitored at [M+H](+)m/z 498-->416
      and 430-->372 in positive electrospray ionization (ESI) mode for cymipristone and
      IS, respectively. Linearity was established for the range of concentrations 0.5
      100 ng/ml with a coefficient correlation (r) of 0.9996. The lower limit of
      quantification (LLOQ) was identifiable and reproducible at 0.5 ng/ml. The
      validated method was successfully applied to study the pharmacokinetics of
      cymipristone in healthy Chinese female subjects.

PMID- 20149767
TI  - [Prevalence and predictive factors of parietal cell antibody positivity in
      autoimmune thyroid disease].
AB  - BACKGROUND AND OBJECTIVES: Our aim was to evaluate the prevalence of parietal
      cell antibodies (PCA) in patients with autoimmune thyroid disease (ATD). MATERIAL
      AND METHODS: We performed a descriptive, cross-sectional study of patients with
      ATD. The presence of PCA was determined. Elevated antithyroid antibodies (ATAs)
      were defined as those higher than the 75th percentile of distribution.
      Multivariate logistic regression models were built to assess the independent
      contribution of the following variables to PCA positivity: age, sex, hemoglobin,
      medium corpuscular volume (MCV), dose/Kg of levothyroxine (LT4), disease duration
      and elevated ATA levels. RESULTS: A total of 148 patients were included (137
      females). The mean age was 45.7 (SD 15) years and disease duration was 4.5 (SD 4)
      years. Forty-three patients (29%) with Graves' disease and 105 (71%) with primary
      hypothyroidism were included. The 75th percentile of distribution was 420U/ml for
      anti-peroxidase antibodies and 200U/ml for anti-thyroglobulin antibodies. PCA
      positivity was found in 30 patients, with an overall prevalence of 20.3%. PCA
      positivity with titers higher than 1/640 was found in 19 patients (12.8%). The
      only independent predictive factor of PCA positivity was the presence of elevated
      levels of ATAs (odds ratio (OR)=3; 95% confidence interval (CI): 1.1-8.6;
      p=0.04). The only independent predictive factor of PCA positivity at titers
      >/=1/640 was also the presence of elevated levels of ATAS (OR=7.3; 95% CI: 1.6
      32.7; p=0.009). CONCLUSIONS: The prevalence of PCA positivity in patients with
      ATD was 20%. Elevated levels of ATAs increase the risk of PCA positivity.

PMID- 20149768
TI  - [Out-of-hospital cardiorespiratory arrest. What has changed since the 2005
      recommendations?].

PMID- 20149769
TI  - [Are parents present during invasive procedures? Assessment in 32 Spanish
      hospitals].
AB  - INTRODUCTION: Parental participation in medical decisions involving their
      children is essential and family presence during invasive procedures (IP) is
      fundamental. OBJECTIVES: 1) To determine the frequency of parental presence
      during different IP in Spanish Paediatrics Emergency Departments (PED). 2) To
      assess the reasons for restricting parental presence. 3) To evaluate the
      agreement of health care professionals with regards to parental presence.
      MATERIALS AND METHODS: Descriptive multicentre study based on questionnaires sent
      to physicians in charge of different Spanish PED. RESULTS: Thirty-two out of 43
      questionnaires were replied. Family presence during IP is never allowed in 11
      hospitals. In the rest, this varies depending on the type of IP: blood sampling
      (15 hospitals), wound suture (14), urethral catheterization (9), lumbar puncture
      (7), intubation (1) and cardiopulmonary resuscitation (1), with no significant
      differences between hospitals. The main arguments for restricting parental
      presence are parental anxiety (26/30) and a lower performance by health personnel
      (23/30). Occasional problems, such as nausea (22/28), have arisen due to family
      presence. The interviewed physicians in charge think that health care
      professionals' agreement rates for parental presence decrease significantly with
      the increasing invasiveness of the procedure. Two hospitals have a working group
      and one a specific protocol to address parental presence. CONCLUSIONS: Parental
      presence during IP is limited in Spanish PED, due to parental anxiety and is
      detrimental to the success of the procedure. Physicians and nurses disagree with
      family presence, especially during the most invasive procedures.

PMID- 20149770
TI  - [Ectopia cordis].

PMID- 20149771
TI  - [Recurrent urine infections: "It's not reflux, it's the bladder"].

PMID- 20149772
TI  - [In defence of paediatrics].

PMID- 20149773
TI  - Breach procedure for axillary hyperhidrosis.

PMID- 20149774
TI  - Lateral calcaneal artery as a recipient pedicle for microsurgical foot
      reconstruction.
AB  - In the microsurgical reconstruction of the foot, anterior tibial artery-dorsalis
      pedis artery and posterior tibial artery-plantar artery are mainly used as
      recipient arterial pedicles. These arteries are the main sources for foot
      circulation and the preservation of these arterial circulations is very
      important. Although the end-to-side technique or the flow-through technique is
      selected for the microsurgical anastomosis, the possibility of injury to the
      circulation of these main arteries exists. We showed the availability of this
      artery with an angiographic injection study in five fresh cadavers as a reliable
      recipient artery. We also used the lateral calcaneal artery as a recipient
      pedicle in foot reconstruction without sacrificing the main circulation in two
      clinical cases. The diameters at the level of the calcaneus were 1.3 mm and 1.5
      mm, respectively.

PMID- 20149775
TI  - Re: Plastic, reconstructive and aesthetic surgeon: Impact of managing perceptions
      on aesthetic publications.

PMID- 20149777
TI  - ?

PMID- 20149776
TI  - Pakistan National Diabetes Survey: prevalence of glucose intolerance and
      associated factors in the Punjab Province of Pakistan.
AB  - AIMS: The prevalence of diabetes mellitus and impaired glucose tolerance (IGT)
      and their relationship to age and obesity were estimated in Punjab, Pakistan by a
      population-based survey done in 1998. METHODS: Oral glucose tolerance tests were
      performed in a stratified random sample of 1852 adults aged >or=25 years. The
      diagnosis of diabetes and IGT were made on the basis of WHO criteria. RESULTS:
      The prevalence of diabetes was 12.14% in males and 9.83% in females. Overall
      total glucose intolerance (diabetes and IGT) was present in 16.68% males and
      19.37% females. Central obesity, hypertension and positive family history were
      strongly associated with diabetes. CONCLUSIONS: These results indicate that the
      prevalence of glucose intolerance is high in the studied population and
      comparable with the published data from the other three provinces of Pakistan
      i.e. Sindh, Baluchistan and North West Frontier Province, studied by the same
      group.

PMID- 20149778
TI  - Patients in a permanent vegetative state or minimally conscious state in the
      Maine-et-Loire county of France: A cross-sectional, descriptive study.
AB  - PURPOSES: To determine how many patients in a permanent vegetative state or a
      minimally conscious state are living in healthcare institutions in the Maine-et
      Loire county of western France. To evaluate patient management, physical
      complications, problems encountered by nursing staff and the patient care teams'
      wishes. PATIENTS AND METHODS: We performed a cross-sectional, descriptive study
      in physical medicine and rehabilitation departments, nursing homes, geriatric
      units and local hospitals. All patients and their medical records were examined
      by the same investigator. A questionnaire for carers was used to evaluate nursing
      tasks and a second questionnaire for head nurses served to assess staff needs and
      the patient care teams' wishes. RESULTS: Thirteen patients were identified. Four
      were in a permanent vegetative state and nine were in a minimally conscious
      state. Ten patients were cared for in geriatric units, one in a physical medicine
      and rehabilitation department and two in local hospitals. All patients displayed
      limited joint angle ranges. All the patient care teams reported practical
      difficulties and ethical issues. DISCUSSION: Our survey highlighted the variety
      of care scenarios for patients in a permanent vegetative state or a minimally
      conscious state. It revealed practical difficulties and, above all, ethical
      questions. The present work could serve as a basis for implementation of a
      recently issued French government circular on defining specific wards for these
      patients.

PMID- 20149779
TI  - Microchip electrophoresis for monitoring covalent attachment of poly(ethylene
      glycol) to proteins.
AB  - A microchip electrophoretic method was applied to monitor and characterize the
      covalent attachment of poly(ethylene glycol) (PEGylation) of two proteins, alpha
      lactalbumin and bovine serum albumin, using several poly(ethylene glycol) (PEG)
      derivatives with molecular weights from 1 to 20 kDa. This method effectively
      separated multi-PEGylated proteins in a size-based manner and allowed monitoring
      of the PEGylation pattern with the advantages of high speed, minimal sample
      consumption, and high reproducibility. Microchip electrophoresis would be a very
      useful tool for protein PEGylation studies such as reaction monitoring, purity
      checks, and characterization of PEGylated protein products.

PMID- 20149780
TI  - Strategies to increase the reproducibility of protein fibrillization in plate
      reader assays.
AB  - There is great interest in developing reproducible high-throughput screens to
      identify small molecular inhibitors of protein fibrillization and aggregation for
      possible therapy against deposition diseases such as Alzheimer's and Parkinson's
      (PD). We have made a methodical analysis of factors increasing the
      reproducibility of the fibrillization of alpha-synuclein (alphaSN), a 140-amino
      acid protein implicated in PD and notorious for its erratic fibrillization
      behavior. Salts and polyanionic polymers do not significantly improve the quality
      of the assay. However, an orbital agitation mode in the plate reader is a crucial
      first step toward reproducible alphaSN fibrillization. Higher reproducibility is
      achieved by the addition of glass beads, as evaluated by the percentage standard
      deviation of the nucleation and elongation rate constants and the end-stage
      fluorescence intensity of the fibril-binding dye thioflavin T (ThT). The highest
      reproducibility is obtained by either seeding the solution with preformed fibrils
      or by adding submicellar amounts of sodium dodecyl sulfate (SDS), where we obtain
      percentage standard deviations of 3-4% on the end ThT level. We conclude that
      there are multiple ways to achieve satisfactory levels of reproducibility,
      although the different conditions used to induce aggregation may lead to
      different fibrillization pathways.

PMID- 20149781
TI  - SP1 is required for basal activation and chromatin accessibility of CD151
      promoter in liver cancer cells.
AB  - CD151 plays an important role in liver cancer metastasis. The mechanism on how
      CD151 is expressed remains unclear. Here we have identified SP1 is a protein
      functioning in constitutive activation of CD151. Applying a PCR-based chromatin
      accessibility assay, an open chromatin conformation was discovered localized
      around the transcription start site of the CD151 gene. Deletion constructs of the
      5' flanking region were fused to a luciferase reporter gene. After transient
      transfection in HepG2 and Hep3B cells, a minimal region -171/-53 bearing three
      SP1-binding sites was identified as the core promoter. Results obtained from
      electrophoretic mobility shift and chromatin immunoprecipitation assays
      demonstrated that SP1 is bound to the core promoter. Deletion of SP1 consensus
      sequence resulted in the total loss of the promoter activity. Moreover, knockdown
      of SP1 reduced both CD151 promoter activity and chromatin accessibility.
      Conclusively, SP1 is pivotal to CD151 transcription partly via the construction
      of a local open chromatin configuration across the promoter.

PMID- 20149782
TI  - Activation of the A(3) adenosine receptor inhibits fMLP-induced Rac activation in
      mouse bone marrow neutrophils.
AB  - Adenosine is released from injured or hypoxic tissues where it exerts numerous
      anti-inflammatory effects including suppression of neutrophil functions. Although
      most previous work has implicated the A(2A)AR, we have recently shown that
      selective activation of the abundantly expressed A(3)AR inhibits neutrophil
      superoxide production and chemotaxis providing a potential mechanistic
      explanation for the efficacy of A(3)AR agonists in experimental animal models of
      inflammation. In this study, we hypothesized that the A(3)AR suppresses
      neutrophil functions by inhibiting the monomeric GTPase Rac, a central regulator
      of chemokine-directed neutrophil migration and superoxide production. We found
      that pre-treating neutrophils with the highly selective A(3)AR agonist CP-532,903
      reduced fMLP-induced Rac activation using an ELISA-based assay that detects all
      three Rac isoforms. CP-532,903 also inhibited fMLP-induced F-actin formation, a
      downstream effector function of Rac relevant to neutrophil migration, but not
      activation of ERK1/2 or p38. Pre-treating neutrophils with CP-532,903 did not
      stimulate cAMP production or alter fMLP-induced calcium transients, implicating
      that A(3)AR stimulation does not inhibit Rac activation or neutrophil activities
      by suppressing Ca(2+) signaling, elevating the intracellular concentration of
      cAMP, or by cross-desensitizing fMLP receptors. Our results suggest that
      activation of the A(3)AR signals to suppress neutrophil functions by interfering
      with the monomeric GTPase Rac, thus contributing to the ant-inflammatory actions
      of adenosine.

PMID- 20149783
TI  - Calcitonin gene-related peptide- and adrenomedullin-induced facilitation of
      calcium current by different signal pathways in nucleus tractus solitarius.
AB  - Calcitonin gene-related peptides (CGRP) and adrenomedullin (ADM) belong to the
      calcitonin family of peptides and are structurally related. Both peptides are
      found in the neurons of the CNS and play a role in many neuronal functions,
      including the control of blood pressure. The nucleus tractus solitarius (NTS) is
      known to play a major role in the regulation of cardiovascular, respiratory,
      gustatory, hepatic and swallowing functions. Recently, hypotension and
      bradycardia were observed after CGRP and ADM injection in the NTS. Voltage
      dependent Ca(2+) channels (VDCCs) serve as crucial mediators of membrane
      excitability and Ca(2+)-dependent functions, such as neurotransmitter release,
      enzyme activity, and gene expression. The purpose of this study is to investigate
      the effects of CGRP and ADM on VDCC currents (I(Ca)) carried by Ba(2+) (I(Ba)) in
      the NTS, using patch-clamp recording methods. Application of CGRP and ADM caused
      facilitation of I(Ba) in a concentration-dependent manner. Intracellular dialysis
      of the anti-Galpha(s)-protein antibody attenuated CGRP-induced facilitation of
      I(Ba). Intracellular dialysis of the anti-Galpha(i)-protein antibody attenuated
      ADM-induced facilitation of I(Ba). Pretreatment with SQ22536 (an adenylate
      cyclase inhibitor) and intracellular dialysis of PKI(5-24) (a protein kinase A
      inhibitor) attenuated CGRP-induced facilitation of I(Ba). In contrast,
      pretreatment with PD98,059 (a mitogen-activated protein kinas inhibitor)
      attenuated ADM-induced facilitation of I(Ba). Mainly L-type VDCCs were
      facilitated by both CGRP and ADM. These results indicate that CGRP facilitates L
      type VDCCs via Galpha(s)-protein involving adenylate cyclase and protein kinase
      A. In contrast, ADM facilitates L-type VDCCs via Galpha(i)-protein involving
      mitogen-activated protein kinase in the NTS.

PMID- 20149784
TI  - Changes in firing rate and pattern of GABAergic neurons in subregions of the
      substantia nigra pars reticulata in rat models of Parkinson's disease.
AB  - The substantia nigra pars reticulata (SNr) plays a key role in the
      pathophysiology of Parkinson's disease (PD). It has been well documented that the
      SNr is not a homogeneous structure, and the lateral and medial subregions of the
      SNr receive different projections from the sensorimotor and limbic striatum,
      respectively. However, specific changes in firing activity of SNr subregions in
      PD remain unclear. In the present study, the spontaneous firing activity of
      GABAergic neurons in the lateral and medial SNr of rats with unilateral 6
      hydroxydopamine lesions of the substantia nigra pars compacta (SNc) or medial
      forebrain bundle (MFB) has been examined. Extracellular recordings indicated that
      the firing rate of lateral SNr neurons increased significantly and firing pattern
      of these neurons changed towards more irregular and bursty after SNc or MFB
      lesions compared to normal rats. In contrast, the firing rate and pattern of
      medial SNr neurons in rats with SNc lesions were unaltered when compared with
      that of normal rats. However, MFB lesions in rats decreased the firing rate of
      medial SNr neurons and firing pattern of these neurons changed towards more
      bursty. In addition, SNc lesions in rats increased the firing rate of the neurons
      with regular and irregular firing patterns within lateral but not in medial SNr,
      while the firing rate of the neurons within lateral and medial SNr with each
      firing pattern was not altered after MFB lesions. These results suggest that
      GABAergic neurons of SNr subregions have differential change of firing activity
      in the pathophysiology of PD.

PMID- 20149785
TI  - Differential distribution of group I metabotropic glutamate receptors in
      developing human cortex.
AB  - Neuronal and glial cells in human cerebral cortex are enriched in group I
      metabotropic glutamate receptors (mGluRs). Developmental regulation of mGluRs has
      been shown in rodent brain and recent studies suggest an involvement of mGluR
      mediated glutamate signaling in the proliferation and survival of neural
      progenitor cells. In the present study, we have investigated the expression and
      cell-specific distribution of group I mGluRs (mGluR1alpha and mGluR5) during
      prenatal human cortical development. mGluR5 was expressed in developing human
      cortex from the earliest stages tested (9 gestational weeks, GW), with strong
      expression in the ventricular/subventricular zones. mGluR1alpha immunoreactivity
      (IR) was observed in the cortical plate at 13GW and persisted throughout the
      prenatal development. Both receptors were expressed in pyramidal neurons in the
      first postnatal year. Group I mGluRs were also expressed by reelin-positive Cajal
      Retzius cells present in the marginal zone/layer I of the developing cortex.
      mGluR5 IR in these cells was observed in the earliest developmental stages and
      persisted during the early postnatal period. In contrast, mGluR1alpha IR was
      detected in Cajal-Retzius cells during the late phase of prenatal development.
      These findings show a differential expression pattern of group I mGluR subtypes,
      suggesting a role for both receptors in the early stages of corticogenesis with,
      however, a different contribution to human cortical developmental events.

PMID- 20149786
TI  - Application of laccase-mediator system (LMS) for the degradation of
      organophosphorus compounds.
AB  - Degradation of organophosphorus compounds was achieved in the presence of
      purified fungal laccase from Trametes versicolor and a small molecular weight
      redox mediator (ABTS). This laccase-mediator system (LMS) catalyzed degradation
      of VX, PhX and VR while had no apparent effect on CVX, ecothiophate or demeton.
      Inhibition of ABTS oxidation was shown with VX, PhX, VR and CVX. Results with CVX
      suggest either no degradation subsequent to interaction with the laccase active
      site or the formation of a new toxic compound. PhX degradation was also monitored
      by mass spectroscopy, a method that allowed us to identify certain intermediates
      formed during OP degradation. Altogether, results underline the importance of the
      OP nitrogen atom at beta-position and of its substituents, even though the
      intimate mechanism of laccase-catalyzed degradation is not yet known.

PMID- 20149787
TI  - Protective effects of diosgenin in the hyperlipidemic rat model and in human
      vascular endothelial cells against hydrogen peroxide-induced apoptosis.
AB  - Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis-associated
      conditions in cardiovascular diseases. Oxidative stress, as a main risk factor
      causes vascular endothelial cell apoptosis, which is implicated in the
      pathogenesis of cardiovascular disorders. Diosgenin, an aglycone of steroidal
      saponins, has been reported to exert anti-proliferative and proapoptotic actions
      on cancer cells widely. In this study, we propose that diosgenin can protect the
      hyperlipidemic rats and prevent endothelial apoptosis under oxidative stress. We
      investigated the hypolipidemic and antioxidative effects of diosgenin on rats fed
      with high cholesterol and high fat diet for 6 weeks. Serum total cholesterol
      (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), glutathione
      peroxidase (GSH-PX), nitric oxide synthase (NOS), hepatic malondialdehyde (MDA),
      lipoprotein lipase (LPL), hepaticlipase (HL) and superoxide dismutase (SOD)
      activities were evaluated. Then we explored the effects and mechanism of
      diosgenin against hydrogen peroxide-induced apoptosis of human vein endothelium
      cells (HUVECs). Intracellular reactive oxygen species (ROS), glutathione (GSH),
      nitric oxide (NO), DNA fragment formation and mitochondrial membrane potentials
      (DeltaPsim) were determined. Diosgenin treatment increased LPL, HL, SOD, GSH-PX
      and NOS activities, thus attenuated oxygen free radicals, decreased MDA, TC, TG
      and LDL-C levels in hyperlipidemic rats. Diosgenin pretreatment significantly
      attenuated H(2)O(2)-induced apoptosis in HUVECs, intracellular ROS, GSH
      depletion, DNA fragment formation, and restored NO, DeltaPsim. These results
      suggested that diosgenin is a very useful compound to control hyperlipidemia by
      both improving the lipid profile and modulating oxidative stress and prevent
      H(2)O(2)-induced apoptosis of HUVECs, in partly through regulating mitochondrial
      dysfunction pathway.

PMID- 20149788
TI  - Measure of expression of mitochondrial related genes in human mononuclear blood
      cells, adipose white tissue and smooth muscle cells.
AB  - BACKGROUND: The role of mitochondrial dysfunction is currently studied
      intensively, but the cumbersome procedure of obtaining tissue from humans has
      restricted the number of subjects studied. Therefore, the aim of the present
      study was to examine the expression of mitochondrial related genes in blood cells
      from humans and to compare the results with measurements of mitochondrial
      membrane potential known to be regulated by thyroid hormones. METHODS: In a group
      of 17 healthy women subscribed for hysterectomy on a benign basis, muscle tissue,
      fat tissue samples and blood specimens were obtained. Mitochondrial mass and
      membrane potential was examined in peripheral blood monocytes by flow cytometry.
      Gene expression of PGC-1alpha, PGC-1beta, NFR-1, NRF-2 and TFAM was determined by
      real-time PCR. RESULTS: All genes were expressed in the 3 tissues examined,
      though with different magnitude. Most genes were expressed in mononuclear blood
      cells at a magnitude comparable to that in white adipose tissue. Furthermore, a
      significant correlation was observed between PGC-1beta and Mitochondrial Membrane
      Potential (MMP) and Mitochondrial Mass (MM). CONCLUSION: Measurement of
      expression of mitochondrial related genes in human mononuclear blood cells may be
      useful for examining mitochondrial function and regulation by thyroid hormones in
      humans.

PMID- 20149789
TI  - The role of FGF-signaling in early neural specification of human embryonic stem
      cells.
AB  - The mechanisms that govern human neural specification are not completely
      characterized. Here we used human embryonic stem cells (hESCs) to study the role
      of fibroblast growth factor (FGF)-signaling in early human neural specification.
      Differentiation was obtained by culturing clusters of hESCs in chemically-defined
      medium. We show that FGF-signaling, which is endogenously active during early
      differentiation of hESCs, induces early neural specification, while its blockage
      inhibits neuralization. The early neuralization effect of FGF-signaling is not
      mediated by promoting the proliferation of existing neural precursors (NPs) or
      prevention of their apoptosis. The neural instructive effect of FGF-signaling
      occurs after an initial FGF-independent differentiation into primitive ectoderm
      like fate. We further show that FGF-signaling can induce neuralization by a
      mechanism which is independent of modulating bone morphogenic protein (BMP)
      signaling. Still, FGF-signaling is not essential for hESC neuralization which can
      occur in the absence of FGF and BMP-signaling. Collectively, our data suggest
      that human neural induction is instructed by FGF-signaling, though neuralization
      of hESCs can occur in its absence.

PMID- 20149791
TI  - Illuminating the ubiquitin/proteasome system.
AB  - The ubiquitin/proteasome system (UPS) is responsible for the regulated processive
      degradation of proteins residing in the cytosol, nucleus, and endoplasmic
      reticulum. The two central players are ubiquitin, a small protein that is
      conjugated to substrates, and the proteasome, a large multi-subunit proteolytic
      complex that executes degradation of ubiquitylated proteins. Ubiquitylation and
      proteasomal degradation are highly dynamic processes. During the last decade,
      many researchers have started taking advantage of fluorescent proteins, which
      allow studying the dynamic nature of this system in the context of its natural
      environment: the living cell. In this review, we will summarize studies that have
      implemented this approach to examine the UPS and discuss novel insights in the
      dynamic organization of the UPS.

PMID- 20149790
TI  - Norepinephrine and nitric oxide promote cell survival signaling in hippocampal
      neurons.
AB  - Nitric oxide (NO), physical exercise and/or antidepressant drugs, through the
      increased release of norepinephrine and brain-derived neurotrophic factor (BDNF),
      have been shown to exert profound protective, pro-survival effects on neurons
      otherwise compromised by injury, disease, prolonged stress, and subsequent
      depression in vivo. We sought, therefore, to evaluate such survival and
      neuroprotection in hippocampal neurons in culture, which, in an analogous model
      of in vivo cellular stress, was deprived of several vital nutrients. We assessed
      pro-survival outcomes following the application of norepinephrine or the
      noradrenergic partial agonist, clonidine, a general nitric oxide synthase
      inhibitor and NO donor, using a cell survival assay and quantitative Western
      blotting of the survival signaling molecules, BDNF, P-CREB, P-Akt, and P-MAPK in
      hippocampal neuronal lysates. We demonstrate that norepinephrine, clonidine, the
      NO donor and various combinations of these drugs increased cell survival and the
      immunoreactivity of the four survival signaling molecules in the face of nutrient
      deprivation stress, whereas the NO synthase inhibitor, and each of several
      survival signaling pathway inhibitors all decreased cell survival even below that
      of controls without nutrient supplementation. These results demonstrate that
      conditions that make cells vulnerable to environmental/toxic insult can be offset
      by norepinephrine and its related drugs or by NO donors and exacerbated by drugs
      that specifically inhibit a key survival signaling pathway. These results
      indicate that pharmacological intervention can promote neuroprotection and
      survival signaling in the face of nutrient withdrawal, but that this may require
      that several pathways remain intact.

PMID- 20149792
TI  - Imatinib has a fatal impact on morphology, pairing stability and survival of
      adult Schistosoma mansoni in vitro.
AB  - Schistosomes cause bilharzia (schistosomiasis), one of the most prevalent
      parasitic diseases for human and animals worldwide. Praziquantel (PZQ) is the
      only widely used drug for treatment and control of this parasitemia. Since a
      vaccine is not yet available, and in light of emerging resistance against PZQ,
      the search for alternatives has high priority. Here we present that Imatinib, a
      compound used in human cancer therapy (Gleevec; STI-571), significantly affected
      schistosome morphology and physiology in vitro. Besides its negative effect on
      gonad development and pairing stability, Imatinib led to pathological alterations
      of the gastrodermis, which finally caused the death of the parasite.

PMID- 20149793
TI  - Australian dingoes are definitive hosts of Neospora caninum.
AB  - To provide objective data on the potential role of dingoes (Canis lupus dingo) in
      the life cycle of Neospora caninum in Australia, the production of N. caninum
      oocysts by experimentally infected canids was investigated. Three dingo pups
      raised in captivity and three domestic dogs were fed tissue from calves infected
      with an Australian isolate of N. caninum, Nc-Nowra. Oocysts of N. caninum,
      confirmed by species-specific PCR, were shed in low numbers by one dingo pup at
      12-14 days p.i. The remaining animals did not shed oocysts. Furthermore, the
      blood from two out of three dingoes tested positive for DNA of N. caninum using
      PCR tests at 14 and 28 days p.i. Oocyst shedding from the intestinal tract of a
      dingo demonstrates that dingoes are definitive hosts of N. caninum and horizontal
      transmission of N. caninum from dingoes to farm animals and wildlife may occur in
      Australia.

PMID- 20149794
TI  - Comparison of polyclonal expansion methods to improve the recovery of cervical
      cytobrush-derived T cells from the female genital tract of HIV-infected women.
AB  - Cervical cytobrushing is a useful and non-invasive method for obtaining mucosal
      mononuclear cells from the female genital tract, but yields few cells. The aim of
      this study was to compare in vitro expansion protocols (anti-CD3, anti-CD3/CD28
      or Dynal anti-CD3/CD28 beads) and cytokine combinations (IL-2, IL-7 and IL-15) to
      improve cervical T cell yields and viability. Eighteen HIV-infected women were
      included in this study to compare methods for polyclonal expansion of T cells
      from the female genital tract and blood. Comparison of T cell yields, viability
      and maturational status (by differential staining with CD45RO, CCR7 and CD27) was
      determined following 7 days of in vitro expansion. Anti-CD3 and IL-2 resulted in
      a 4.5-fold (range 3.7-5.3) expansion of cervical CD3+ T cells in 7 days compared
      to day 0. Inclusion of anti-CD28 or addition of IL-7 and IL-15 to this
      combination did not improve expansion. Culturing cells with Dynal beads (1:1) and
      IL-2, IL-7 and IL-15 gave rise to the highest yields after 7 days in both blood
      (7.1-fold) and cervix (5.6-fold). While expansion with anti-CD3 led to the
      accumulation of effector memory T cells (CD45RO+CCR7-CD27-), expansion with
      Dynabeads selected for accumulation of central memory T cells
      (CD45RO+CCR7+CD27+). We conclude that in vitro expansion with Dynabeads (1:1) in
      the presence of IL-2, IL-7 and IL-15 resulted in the greatest increase in viable
      T cells from both blood and cytobrush. Irrespective of the expansion method used,
      the T cell memory profile was altered following expansion.

PMID- 20149795
TI  - A simple method to detect Toxoplasma gondii-specific cytotoxic T cells in vivo.
AB  - Cytotoxic T cells (CTLs) are an important component of adaptive immunity. The
      study of antigen-specific CTLs in vivo is desirable yet difficult. Identification
      of the class I-restricted peptide used by CTLs for target recognition is often
      required for detailed studies, but is generally not known for most antigens.
      Toxoplasma gondii is a medically important, obligate intracellular parasite and
      is often used as a model for studies of parasite immunology. No class I
      restricted peptides for CTLs are known. We show here a new and convenient method
      to detect T. gondii-specific CTLs in vivo. We engineered T. gondii tachyzoites to
      express the model antigen ovalbumin, for which many useful reagents and
      transgenic mice are available. Using ovalbumin-transgenic T. gondii tachyzoites,
      antigen-specific CTLs were detected in vivo, and at much earlier time points post
      infection than previously reported. This new method has several additional
      advantages over current methods to detect T. gondii-specific CTLs.

PMID- 20149796
TI  - A chymotrypsin-like serine protease cDNA involved in food protein digestion in
      the common cutworm, Spodoptera litura: Cloning, characterization, developmental
      and induced expression patterns, and localization.
AB  - A full-length cDNA (Slctlp2) encoding a chymotrypsin-like serine protease was
      cloned from Spodoptera litura. This cDNA encoded a putative serine protease with
      a predicted molecular mass of 30.6kDa, which contained a serine protease
      catalytic motif GDSGGPL. Temporal and spatial expression of Slctlp2 mRNA and
      protein detected by Northern blotting, RT-PCR, qPCR and Western blotting analyses
      revealed that both Slctlp2 mRNA and protein were mainly present in the foregut
      and midgut of the 5th and 6th instar larvae during the feeding stages. In situ
      hybridization and immunohistochemistry confirmed that both Slctlp2 mRNA and
      protein were predominately present in the midgut. Expression of the gene was not
      induced by bacterial infection. Juvenile hormone III induced the gene expression,
      while 20-hydroxyecdysone had no impact on the expression. The expression of
      Slctlp2 mRNA and protein was down-regulated by starvation but up-regulated by re
      feeding. The SlCTLP2 protein was detected in the lumen residues of the anterior,
      middle and posterior midgut and feces of the feeding 6th instar larvae,
      suggesting that it was secreted from the epithelium into the lumen of the gut.
      The results suggest that this Slctlp2 gene may be involved in digestive process
      of food proteins during the feeding stages of the larval development.

PMID- 20149797
TI  - Protein folding requires crowd control in a simulated cell.
AB  - Macromolecular crowding has a profound effect upon biochemical processes in the
      cell. We have computationally studied the effect of crowding upon protein folding
      for 12 small domains in a simulated cell using a coarse-grained protein model,
      which is based upon Langevin dynamics, designed to unify the often disjoint goals
      of protein folding simulation and structure prediction. The model can make
      predictions of native conformation with accuracy comparable with that of the best
      current template-free models. It is fast enough to enable a more extensive
      analysis of crowding than previously attempted, studying several proteins at many
      crowding levels and further random repetitions designed to more closely
      approximate the ensemble of conformations. We found that when crowding approaches
      40% excluded volume, the maximum level found in the cell, proteins fold to fewer
      native-like states. Notably, when crowding is increased beyond this level, there
      is a sudden failure of protein folding: proteins fix upon a structure more
      quickly and become trapped in extended conformations. These results suggest that
      the ability of small protein domains to fold without the help of chaperones may
      be an important factor in limiting the degree of macromolecular crowding in the
      cell. Here, we discuss the possible implications regarding the relationship
      between protein expression level, protein size, chaperone activity and
      aggregation.

PMID- 20149798
TI  - Structural basis of human CYP51 inhibition by antifungal azoles.
AB  - The obligatory step in sterol biosynthesis in eukaryotes is demethylation of
      sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14
      alpha demethylase) in three sequential reactions. In mammals, the final product
      of the pathway is cholesterol, while important intermediates, meiosis-activating
      sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand
      free and complexed with antifungal drugs ketoconazole and econazole, were
      determined, allowing analysis of the molecular basis for functional conservation
      within the CYP51 family. Azole binding occurs mostly through hydrophobic
      interactions with conservative residues of the active site. The substantial
      conformational changes in the B' helix and F-G loop regions are induced upon
      ligand binding, consistent with the membrane nature of the protein and its
      substrate. The access channel is typical for mammalian sterol-metabolizing P450
      enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51.
      Comparison of the azole-bound structures provides insight into the relative
      binding affinities of human and bacterial P450 enzymes to ketoconazole and
      fluconazole, which can be useful for the rational design of antifungal compounds
      and specific modulators of human CYP51.

PMID- 20149799
TI  - Ribosomes lacking protein S20 are defective in mRNA binding and subunit
      association.
AB  - The functional significance of ribosomal proteins is still relatively unclear.
      Here, we examined the role of small subunit protein S20 in translation using both
      in vivo and in vitro techniques. By means of lambda red recombineering, the rpsT
      gene, encoding S20, was removed from the chromosome of Salmonella enterica var.
      Typhimurium LT2 to produce a DeltaS20 strain that grew markedly slower than the
      wild type while maintaining a wild-type rate of peptide elongation. Removal of
      S20 conferred a significant reduction in growth rate that was eliminated upon
      expression of the rpsT gene on a high-copy-number plasmid. The in vitro phenotype
      of mutant ribosomes was investigated using a translation system composed of
      highly active, purified components from Escherichia coli. Deletion of S20
      conferred two types of initiation defects to the 30S subunit: (i) a significant
      reduction in the rate of mRNA binding and (ii) a drastic decrease in the yield of
      70S complexes caused by an impairment in association with the 50S subunit. Both
      of these impairments were partially relieved by an extended incubation time with
      mRNA, fMet-tRNA(fMet), and initiation factors, indicating that absence of S20
      disturbs the structural integrity of 30S subunits. Considering the topographical
      location of S20 in complete 30S subunits, the molecular mechanism by which it
      affects mRNA binding and subunit docking is not entirely obvious. We speculate
      that its interaction with helix 44 of the 16S ribosomal RNA is crucial for
      optimal ribosome function.

PMID- 20149800
TI  - The paradox of cooperation benefits.
AB  - It seems obvious that as the benefits of cooperation increase, the share of
      cooperators in the population should also increase. It is well known that
      positive assortment between cooperative types, for instance in spatially
      structured populations, provide better conditions for the evolution of
      cooperation than complete mixing. This study demonstrates that, assuming positive
      assortment, under most conditions higher cooperation benefits also increase the
      share of cooperators. On the other hand, under a specified range of payoff
      values, when at least two payoff parameters are modified, the reverse is true.
      The conditions for this paradox are determined for two-person social dilemmas:
      the Prisoner's Dilemma, the Hawks and Doves game, and the Stag Hunt game,
      assuming global selection and positive assortment.

PMID- 20149801
TI  - Vaccine demand driven by vaccine side effects: dynamic implications for SIR
      diseases.
AB  - For infections for which the perceived risk of serious disease is steadily low,
      the perceived risk of suffering some vaccine side effects might become the
      driving force of the vaccine demand. We investigate the dynamics of SIR
      infections in homogeneously mixing populations where the vaccine uptake is a
      decreasing function of the current (or past) incidence, or prevalence, of vaccine
      side effects. We define an appropriate model where vaccine side-effects are
      modelled as functions of the age since vaccination. It happens that the vaccine
      uptake follows its own dynamics independent of epidemiological variables. We show
      the conditions under which the vaccine uptake lands on a globally stable
      equilibrium, or steadily oscillates, and the implications of such behaviour for
      the dynamics of epidemiological variables. We finally report some unexpected
      scenarios caused by trends in vaccine side effects.

PMID- 20149802
TI  - Nitric oxide synthase activation and oxidative stress, but not intracellular zinc
      dyshomeostasis, regulate ultraviolet B light-induced apoptosis.
AB  - AIMS: To investigate the role of nitric oxide synthase (NOS) and intracellular
      free zinc ion (Zn(2+)) in regulation of ultraviolet B light (UVB)-induced cell
      damage and apoptosis. MAIN METHODS: Real-time confocal microscopy measurement was
      used to determine the changes of intracellular free zinc concentration under
      different conditions. Cell apoptotic death was determined using fluorescein
      isothiocyanate (FITC) conjugated-annexin V (ANX5)/PI labeling followed by flow
      cytometry. Western analysis was used to determine cell apoptosis and eNOS
      uncoupling. KEY FINDINGS: UVB induced an elevation of Zn(2+) within 2 min of
      exposure. The UVB-induced intracellular Zn(2+) elevation was dependent on the
      increase of constitutive nitric oxide synthase (cNOS) activity and production of
      superoxide. Removal of Zn(2+) with a lower concentration (<25 microM) of
      N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a Zn(2+)-specific
      chelator, did not induce cell death or prevent cells from UVB-induced apoptosis.
      However, a higher [TPEN] (>50 microM) was cytotoxic to cells, but prevented cells
      from further UVB-induced apoptosis. The higher [TPEN] also induced cNOS
      uncoupling. Furthermore, treating the cells with a membrane permeable superoxide
      dismutase (PEG-SOD) inhibited Zn(2+) release and reduced apoptotic cell death
      after UVB treatment. The results demonstrated a complex and dynamic regulation of
      UVB-induced cell damage. SIGNIFICANCE: Our findings not only advance our
      understanding of the correlations between cNOS activation and Zn elevation, but
      also elucidated the role of cNOS in regulation of oxidative stress and apoptosis
      upon UVB-irradiation.

PMID- 20149803
TI  - Oxytocin stimulates expression of a noncoding RNA tumor marker in a human
      neuroblastoma cell line.
AB  - AIMS: A noncoding RNA, metastasis-associated lung adenocarcinoma transcript 1
      (MALAT1), is upregulated in several malignant tumors. Its expression in
      neuroblastoma, however, is not known, and the regulatory mechanisms of MALAT1
      gene expression have not been elucidated. The aim of this study is to clarify how
      MALAT1 gene expression is altered by extracellular signals in the SK-N-SH
      neuroblastoma cell line and to define its proximal promoter in order to study the
      mechanism of MALAT1 gene expression. METHODS: Transcript amounts were analyzed by
      real-time semiquantitative polymerase chain reaction (qPCR). Genes coregulated
      with MALAT1 were identified by DNA microarray analysis. The structure of the
      MALAT1 transcript was delineated using a tiling microarray, and the 5'-end was
      determined using the rapid amplification of cDNA ends (RACE) method. We
      investigated binding of the cyclic AMP-responsive element binding (CREB)
      transcription factor to the MALAT1 promoter by using chromatin
      immunoprecipitation (ChIP) followed by tiling array analysis, and the results
      were confirmed using ChIP-qPCR. KEY FINDINGS: The posterior pituitary hormone
      oxytocin increased the levels of MALAT1 and immediate early gene transcripts as
      early as 15 min after stimulation. Although the expression of immediate early
      genes returned to basal levels after 3h, MALAT1 transcript levels peaked 6-24h
      after stimulation. We identified a shorter transcriptional initiation site and
      found that CREB binds to the defined proximal promoter of the MALAT1 gene.
      SIGNIFICANCE: The expression of the tumor marker MALAT1 ncRNA is sensitive to
      cell surface receptor activation by oxytocin in a neuroblastoma cell line.

PMID- 20149804
TI  - Serotonin and its 5-HT(2) receptor agonist DOI hydrochloride inhibit the
      oxidative burst in total leukocytes but not in isolated neutrophils.
AB  - AIMS: Serotonin (5-HT) is capable of reducing the oxidative burst of professional
      phagocytes. In this study, we investigated whether 5-HT mediates this modulation
      via 5-HT receptors (5-HTR) or whether this is due instead to 5-HT antioxidative
      properties. MAIN METHODS: The leukocytes or polymorphonuclear leukocytes (PMNL)
      were isolated from human blood, and their ability to produce reactive oxygen
      species (ROS) after 5-HT or its agonist treatment was tested by luminol-enhanced
      chemiluminescence (CL) analysis. KEY FINDINGS: It was found that 5-HTR(2) agonist
      DOI hydrochloride does not have any antioxidative properties, despite its ability
      to inhibit the CL response of activated human total leukocytes. On the other
      hand, DOI hydrochloride was unable to inhibit the CL response of activated human
      PMNL. It seems that the reduction of the oxidative burst of professional
      phagocytes was evoked by the activation of 5-HTR not on the neutrophil surface
      but on the surface of different leukocytes, which produced anti-inflammatory
      cytokines with NADPH oxidase activity modulating properties. SIGNIFICANCE:
      Platelets and activated PMNL are in tight contact at sites of inflammation. 5-HT
      released from platelets might have a protective function against PMNL-derived
      oxidative stress and oxidative damages.

PMID- 20149805
TI  - Identification, purification and partial characterization of a 70kDa inhibitor
      protein of Na(+)/K(+)-ATPase from cytosol of pulmonary artery smooth muscle.
AB  - AIMS: We sought to identify, purify and partially characterize a protein
      inhibitor of Na(+)/K(+)-ATPase in cytosol of pulmonary artery smooth muscle. MAIN
      METHODS: (i) By spectrophotometric assay, we identified an inhibitor of
      Na(+)/K(+)-ATPase in cytosolic fraction of pulmonary artery smooth muscle; (ii)
      the inhibitor was purified by a combination of ammonium sulfate precipitation,
      diethylaminoethyl (DEAE) cellulose chromatography, hydroxyapatite chromatography
      and gel filtration chromatography; (iii) additionally, we have also purified
      Na(+)/K(+)-ATPase alpha(2)beta(1) and alpha(1)beta(1) isozymes for determining
      some characteristics of the inhibitor. KEY FINDINGS: We identified a novel
      endogenous protein inhibitor of Na(+)/K(+)-ATPase having an apparent mol mass of
      approximately 70kDa in the cytosolic fraction of the smooth muscle. The IC(50)
      value of the inhibitor towards the enzyme was determined to be in the nanomolar
      range. Important characteristics of the inhibitor are as follows: (i) it showed
      different affinities toward the alpha(2)beta(1) and alpha(1)beta(1) isozymes of
      the Na(+)/K(+)-ATPase; (ii) it interacted reversibly to the E(1) site of the
      enzyme; (iii) the inhibitor blocked the phosphorylated intermediate formation;
      and (iv) it competitively inhibited the enzyme with respect to ATP. CD studies
      indicated that the inhibitor causes an alteration of the conformation of the
      enzyme. The inhibition study also suggested that the DHPC solubilized Na(+)/K(+)
      ATPase exists as (alphabeta)(2) diprotomer. SIGNIFICANCE: The inhibitor binds to
      the Na(+)/K(+)-ATPase at a site different from the ouabain binding site. The
      novelty of the inhibitor is that it acts in an isoform specific manner on the
      enzyme, where alpha(2) is more sensitive than alpha(1).

PMID- 20149807
TI  - Dopamine on D2-like receptors "reboosts" dopamine D1-like receptor-mediated
      behavioural activation in rats licking for sucrose.
AB  - BACKGROUND: The analysis of licking microstructure provides measures, such as
      duration and number of licking bouts, which might reveal the former an evaluation
      process and the latter an approach response. Dopamine D2-like receptor
      antagonists reduce the duration of licking bouts and mimic the effect of reducing
      sucrose concentration, while conflicting results are reported on the effects of
      dopamine D1-like receptor antagonists. The aim of this study is to examine the
      roles of dopamine D1-like and D2-like receptors in the activation of reward
      associated responses and in reward evaluation, through the study of licking
      microstructure. METHODS: The effects of the dopamine D2-like receptor antagonists
      raclopride (0.025-0.25 mg/kg), the D1-like antagonist SCH 23390 (0.01-0.04 mg/kg)
      and the antipsychotic drug haloperidol (0.02-0.05 mg/kg), have been examined on
      the microstructure of licking for a 10% sucrose solution in rats. RESULTS: The
      results confirm that dopamine D2-like receptor antagonists reduce the duration of
      licking bouts and reveal that while SCH 23390 reduced licking exclusively by
      reducing bout number, raclopride produced on this measure an extinction mimicry
      effect similar to that observed in instrumental responding for different rewards.
      DISCUSSION: These results are consistent with the hypothesis that the level of
      activation of the responses to the reward-associated cues depends on dopamine D1
      like receptor stimulation, and is updated, or "reboosted", on the basis of a
      dopamine D2-like receptor-mediated evaluation process occurring during the
      consummatory transaction with the reward.

PMID- 20149806
TI  - Hemato-vascular origins of endothelial progenitor cells?
AB  - Numerous studies have suggested the presence of precursor cells in various
      tissues and organs with potential to differentiate into endothelial and mural
      cells, and contribute to blood vessel formation in different physiological and
      pathological circumstances. Although there is still a lack of consensus in the
      field regarding the origin, and phenotypic and functional characteristics of
      putative vascular progenitor cell populations, all agree that further studies are
      needed to fully explore and exploit their great potential as cell therapy for
      vascular diseases, as modulators of postnatal blood vessel formation, and as
      disease biomarkers. Herein, we will review the phenotypic and functional
      characteristics of endothelial progenitor/precursor cell types thought to be
      derived from the hematopoietic and vascular systems and contribute to postnatal
      blood vessel formation, and discuss their potential lineage relationships.

PMID- 20149808
TI  - Tau protein and tau aggregation inhibitors.
AB  - Alzheimer disease is characterized by pathological aggregation of two proteins,
      tau and Abeta-amyloid, both of which are considered to be toxic to neurons. In
      this review we summarize recent advances on small molecule inhibitors of protein
      aggregation with emphasis on tau, with activities mediated by the direct
      interference of self-assembly. The inhibitors can be clustered in several
      compound classes according to their chemical structure, with subsequent
      description of the structure-activity relationships, showing that hydrophobic
      interactions are prevailing. The description is extended to the pharmacological
      profile of the compounds in order to evaluate their drug-likeness, with special
      attention to toxicity and bioavailability. The collected data indicate that
      following the improvements of the in vitro inhibitory potencies, the
      consideration of the in vivo pharmacokinetics is an absolute prerequisite for the
      development of compounds suitable for a transfer from bench to bedside.

PMID- 20149809
TI  - Housing environment influences the need for pain relief during post-operative
      recovery in mice.
AB  - The impact of invasive experimental procedures on perceived stress and pain may
      be dependent on both physical and social environmental conditions. The aim of
      this study was to evaluate the effects of a physically and a socially enriched
      environment on the need for pain relief following painful experimental
      procedures. A non-invasive method to administer analgesics post-operatively is by
      means of self-administration which is a feasible objective method to measure
      perceived pain during the post-operative recovery period. In the present study
      eight groups of mice housed in different conditions underwent the surgical
      procedure of caecal manipulation or only exposure to anaesthesia. After surgery
      the mice were given the choice to self-administer an analgesic available in one
      of their water bottles during two post-operative weeks. It was shown that
      socially enriched mice drank i.e. self-administered, less from the analgesic
      containing water than the non-enriched and socially deprived groups. Mice that
      underwent operation self-administered more analgesic than mice that received only
      anaesthesia without operation. The findings indicate that the recovery
      environment can contribute positively to attenuate the need for pain relief in
      animals submitted to invasive procedures.

PMID- 20149810
TI  - Partner preference: assessing the role of the female goat.
AB  - For domestic ruminants, the male is thought to have the control over mate choice.
      The aim of this study was to assess the potential role the female goat plays in
      choosing a sexual partner. Approach frequency and proximity time to various
      social or sexual stimuli in a Y-maze apparatus were used as partner preference
      assessment parameters. Ovariectomized females were either induced into estrus
      (n=8) or induced into anestrus (n=8) and exposed to various goal stimuli - intact
      unfamiliar females (estrous and diestrous), intact males, and neutral (empty) in
      six separate trials. Total arm entries and time spent within one body length of
      the goal (proximity time - used to calculate preference scores) were recorded for
      subjects. With a male present, anestrous subjects had significantly more total
      arm entries than estrous subjects. Estrous subjects showed a significant
      preference for the male goal (M) versus the estrous female (ES), diestrous female
      (DS), and empty goals, respectively. Estrous subjects also showed a preference
      for the ES and DS goals when one goal was left empty. Anestrous subjects showed a
      preference for the goal containing ES, DS, and M compared to empty goals. They
      also showed a preference for ES vs. DS. The Y-maze is a tool that can be used to
      assess sexual and social partner preferences in female goats. The role the female
      plays in choosing a partner may be much greater than previously considered.

PMID- 20149811
TI  - Fluoxetine does not prevent interspecific mating between two hamster species.
AB  - In a recent study we showed that female Syrian hamsters (Mesocricetus auratus)
      from a laboratory stock readily mated with male Turkish hamsters (M. brandti). We
      hypothesized that captivity and/or unconscious selection of the most receptive
      females by researchers or animal caretakers results in heightened female sexual
      receptivity and reduces the tendency to reject heterospecific males. To test this
      hypothesis, we decided to decrease female receptivity by injection of fluoxetine,
      which increases the levels of serotonin in a number of brain loci, including
      areas involved in mediating sexual behavior, and determine whether such a
      decrease in receptivity would result in better discrimination of heterospecific
      males and rejection of such males as mates. We treated estrous female Syrian
      hamsters with 20mg/kg fluoxetine or vehicle and paired them with both a
      conspecific and a heterospecific male (Turkish hamster) in two sequential tests.
      All females showed similar behavior - they exhibited lordosis toward both
      conspecific and heterospecific males. We did not observe any sign of aggression.
      Latency to display lordosis and the duration of lordosis were not affected by
      fluoxetine. Fluoxetine thus did not have an effect on the behavior of females
      toward conspecific or heterospecific males. Independent of treatment (fluoxetine
      or vehicle injection), females did display lordosis significantly faster and for
      a longer duration in the presence of a conspecific male, even though these
      differences were small.

PMID- 20149812
TI  - Rapid responses to steroid hormones. Preface.

PMID- 20149813
TI  - Transcriptional regulation of Fhl1 by estradiol in rat myoblastocytes.
AB  - Fhl1 (Four and a Half LIM domain 1) regulates muscle growth and development. In
      addition, skeletal myoblast growth is significantly affected by gender
      differences, implicating estrogen in the regulation of muscle development. We
      sought to determine if estrogen influences Fhl1 gene expression levels in rat
      L6GNR4 myoblastocytes that express the estrogen receptor beta (ERbeta), while
      luciferase assay, electrophoretic mobility shift assay (EMSA), and chromatin
      immunoprecipitation (ChIP) assay were employed to confirm the interaction between
      ERbeta and Fhl1. Treatment of L6GNR4 cells with physiological levels of 17beta
      estradiol (E2) results in markedly decreased endogenous Fhl1 expression.
      Tamoxifen, an ER antagonist, partially reverses E2-mediated Fhl1 down-regulation
      in L6GNR4 cells. Furthermore, luciferase assay and EMSA identified a novel
      promoter region of Fhl1 that directly interacts with ERbeta. ChIP of the ERbeta
      Fhl1 promoter complex from L6GNR4 cells confirmed that endogenous ERbeta
      interacts with this region. These data indicate that E2 down-regulates Fhl1
      expression through its binding to the ERbeta. This is the first report of a small
      molecule that can affect Fhl1 expression. E2 may therefore be useful in
      developing new strategies for regulating Fhl1 expression and understanding the
      influence of estrogen on muscle growth and development.

PMID- 20149814
TI  - Multi-site adaptation in the presence of infrequent recombination.
AB  - The adverse effect of co-inheritance linkage of a large number of sites on
      adaptation has been studied extensively for asexual populations. However, it is
      insufficiently understood for multi-site populations in the presence of
      recombination. In the present work, motivated by our studies of HIV evolution in
      infected patients, we consider a model of haploid populations with infrequent
      recombination. We assume that small quantities of beneficial alleles preexist at
      a large number of sites and neglect new mutation. Using a generalized form of the
      traveling wave method, we show that the effectiveness of recombination is impeded
      and the adaptation rate is decreased by inter-sequence correlations, arising due
      to the fact that some pairs of homologous sites have common ancestors existing
      after the onset of adaptation. As the recombination rate per individual becomes
      smaller, site pairs with common ancestors become more frequent, making
      recombination even less effective. In addition, an increasing number of sites
      become identical by descent across large samples of sequences, causing reversion
      of the direction of evolution and the loss of beneficial alleles at these sites.
      As a result, within a 10-fold range of the recombination rate, the average
      adaptation rate falls from 90% of the infinite-recombination value down to 10%.
      The entire transition from almost maximum to almost zero may occur at very small
      recombination rates. Interestingly, the strong effect of linkage on the
      adaptation rate is predicted in the absence of average linkage disequilibrium
      (Lewontin's measure).

PMID- 20149815
TI  - Arrested development: high-resolution imaging of foveal morphology in albinism.
AB  - Albinism, an inherited disorder of melanin biosynthesis, disrupts normal retinal
      development, with foveal hypoplasia as one of the more commonly associated ocular
      phenotypes. However the cellular integrity of the fovea in albinism is not well
      understood - there likely exist important anatomical differences that underlie
      phenotypic variability within the disease and that also may affect responsiveness
      to therapeutic intervention. Here, using spectral-domain optical coherence
      tomography (SD-OCT) and adaptive optics (AO) retinal imaging, we obtained high
      resolution images of the foveal region in six individuals with albinism. We
      provide a quantitative analysis of cone density and outer segment elongation
      demonstrating that foveal cone specialization is variable in albinism. In
      addition, our data reveal a continuum of foveal pit morphology, roughly aligning
      with schematics of normal foveal development based on post-mortem analyses.
      Different albinism subtypes, genetic mutations, and constitutional pigment
      background likely play a role in determining the degree of foveal maturation.

PMID- 20149816
TI  - Medial forebrain stimulation enhances intracranial nociception and attenuates
      morphine analgesia suggesting the existence of an endogenous opioid antagonist.
AB  - The purpose of this experiment was to test in the rat the hypotheses that
      activation of the brain reward system would attenuate the effects of intracranial
      nociceptive stimulation and would potentiate the antinociceptive effects of
      morphine. In this experiment pain (nociception) was generated by electrical
      stimulation of a brain pain pathway, the mesencephalic reticular formation (MRF)
      of the rat. Reward pathway stimulation was to the medial forebrain bundle at the
      level of the lateral hypothalamus (MFB-LH). Current thresholds for escape from
      MRF stimulation were determined using a modification of the psychophysical
      methods of limits. MRF stimulation was delivered concurrently with different
      intensities of non-contingent MFB-LH stimulation. The effects of morphine and
      saline were determined under all stimulation conditions. Contrary to expectation
      MFB-LH stimulation significantly lowered MRF stimulation escape thresholds.
      Morphine administration elevated MRF thresholds in the absence of MFB-LH
      stimulation. However, this effect was blocked by concurrent MFB-LH stimulation.
      These findings, which mimic the effects of the opiate antagonist naloxone, i.e.,
      potentiating of pain and antagonism of morphine's analgesic effects, suggest the
      presence of an endogenous opiate receptor antagonist.

PMID- 20149817
TI  - Optimization of ultrasonic/microwave assisted extraction (UMAE) of
      polysaccharides from Inonotus obliquus and evaluation of its anti-tumor
      activities.
AB  - Recently, the use of ultrasonic and microwave has attracted considerable interest
      as an alternative approach to the traditional extraction methods. In this paper,
      in order to maximize the yield and purity of polysaccharides from Inonotus
      obliquus, response surface methodology (RSM) was employed to optimize the
      ultrasonic/microwave assisted extraction (UMAE) conditions. The results indicated
      that the optimal conditions for UMAE were 90W microwave power, 50W ultrasonic
      power together with 40kHz ultrasonic frequency, solid/water ratio was 1:20 (W/V)
      and the extracting time was 19min, respectively. Under the optimal conditions,
      the yield and purity of polysaccharides were 3.25% and 73.16%, respectively,
      which are above that of traditional hot water extraction and close to the
      predicted value (3.07% and 72.54%, respectively). These results confirmed that
      ultrasonic/microwave assisted extraction (UMAE) of polysaccharides had great
      potential and efficiency compared with traditional hot water extraction. At the
      same time, the anti-tumor activities of the polysaccharides from I. obliquus with
      UMAE were evaluated. The results suggested that polysaccharides from I. obliquus
      exhibited obvious anti-tumor activities.

PMID- 20149818
TI  - Astragalus polysaccharide and oxymatrine can synergistically improve the immune
      efficacy of Newcastle disease vaccine in chicken.
AB  - Three hundred and sixty 14-day-old chickens were divided into seven groups. The
      chickens, except for blank control group, were vaccinated with Newcastle disease
      vaccine, repeated at 28 days old. At the same time of the first vaccination, the
      chickens in three astragalus polysaccharide-oxymatrine (AP-OM) groups were orally
      administrated respectively with the mixture of AP-OM at high, medium and low
      concentrations, in astragalus polysaccharide (AP) group and oxymatrine (OM)
      group, with corresponding medicine, in non-medicine (NM) control group, with
      equal volume of physiological saline, once a day for 3 successive days. On 14,
      21, 28, 35 and 42 days after the first vaccination, the changes of peripheral
      lymphocyte proliferation and serum antibody titers of the chickens were
      determined by MTT method and hemagglutination inhibition test. On 14, 28 and 42
      days after the first vaccination, the serum IL-2 concentration was determined by
      Enzyme-linked Immunosorbent Assay (ELISA). The results showed that at most time
      points, the lymphocyte proliferation, antibody titers and IL-2 concentrations of
      5 medicine-administrating groups were significantly higher than that of
      corresponding NM group. At some time points, the lymphocyte proliferation,
      antibody titers and IL-2 concentrations in high and medium doses of AP-OM groups
      were significantly or numberly higher than those in AP group and OM group. It
      indicated that AP-OM could significantly improve the immune efficacy of Newcastle
      disease vaccine, astragalus polysaccharide and oxymatrine possessed synergistical
      immunoenhancement.

PMID- 20149819
TI  - A differential proteomics study of Caenorhabditis elegans infected with Aeromonas
      hydrophila.
AB  - The striking similarities between the innate defences of vertebrates and
      invertebrates as well as the amenability of Caenorhabditis elegans for genetic
      analysis, have made this free-living ground nematode a popular model system in
      the study of bacterial pathogenesis. Although genetic studies have brought new
      insights, showing the inducibility and pathogen-specificity of the immune
      response, there is still much to be discovered about the exact mechanisms
      underlying resistance to infection. In this paper a different angle was adopted
      to study host-pathogen interactions in C. elegans. We report the application of
      differential gel electrophoresis (DIGE), combined with mass spectrometry to
      search for proteins that are differentially synthesised in the worm after
      infection with the gram-negative bacterium Aeromonas hydrophila. Given the
      dynamic nature of an immune response, the proteome of C. elegans was investigated
      at three different time-points after infection. A total of 65 differential
      proteins were identified. This study confirms the involvement of galectins, C
      type lectins and lipid binding proteins in the immunity of C. elegans. In
      addition a number of unknown proteins, which might represent important players of
      the worm's defence system, were isolated and identified. This work gives a first
      indication of the complex changes that occur at the protein level during
      infection.

PMID- 20149821
TI  - Conditions for dye-filling of sensory neurons in Caenorhabditis elegans.
AB  - Dye-filling is a common method used to stain Caenorhabditis elegans sensory
      neurons in vivo. While the amphids and phasmids are easy to stain, a subset of
      sensory neurons, the IL2 neurons, are difficult to stain reproducibly. Here we
      examined the conditions under which the IL2 neurons take up the lipophilic
      fluorescent dye DiI. We find that IL2 dye-filling depends on salt concentration,
      but not osmolarity. Low salt prior and during incubation is important for
      efficient dye uptake. Additional parameters that affect dye-filling are the speed
      of shaking during incubation and the addition of detergents. Our modified dye
      filling procedure provides a reliable method to distinguish mutant alleles that
      stain amphids and phasmids, IL2 neurons, or both. An additional benefit is that
      it can also stain the excretory duct. The method allows genetic screens to be
      performed to identify mutants that selectively affect only one of the sensory
      structures or the excretory duct.

PMID- 20149822
TI  - A non-linear regression analysis method for quantitative resolution of the
      stimulus-evoked compound action potential from rodent optic nerve.
AB  - The stimulus-evoked compound action potential (CAP) recorded from rodent optic
      nerve is polyphasic in profile, with total area under the CAP an index of nerve
      function. A decrease in CAP area signifies a decrease in the number of axons
      contributing to the CAP. A disadvantage of considering the CAP a uniform entity
      is that any distinctions between the axon-subpopulations contributing to the
      individual peaks go undetected. We illustrate two instances that demonstrate the
      advantages of resolving the CAP into its constituent peaks. The individual peaks
      of the CAP were quantified using curve-fitting procedures to describe the CAP as
      the sum of multiple Gaussian functions. The first example illustrates that the
      individual peaks comprising the CAP exhibit differential sensitivities to
      glucopenia, suggesting that the axons within the nerve cannot be considered a
      homogeneous population with regard to their metabolic characteristics. The second
      example illustrates that the complex waveform of the CAP recorded from the optic
      nerve of the hypomyelinated rumpshaker mutant mouse, comprising both positive and
      negative overlapping peaks, can be resolved into five individual peaks. In
      conclusion we show that assessing each individual peak of the CAP is a powerful
      analytic tool for identifying heterogeneous profiles of axon-subpopulations in
      the rodent optic nerve.

PMID- 20149823
TI  - Comparison of the predictive validity of the mirror chamber and elevated plus
      maze tests in mice.
AB  - The mirror chamber (MC) is a putative test of anxiety-like behavior in mice, and
      is increasingly popular. Nonetheless, it is unclear whether the observed
      behaviors rely on the presence of mirrored panels. If so, it is unclear whether
      the behaviors are sensitive to clinically effective anxiolytics, and how the test
      compares to the elevated plus maze (EPM) in terms of predictive validity. The
      present studies assessed anxiety-like behaviors in different mouse strains in the
      MC using mirrored and non-mirrored panels, under variable lighting conditions. We
      also assessed the pharmacological validity of the MC and EPM tests, and the
      locomotor properties of active test compounds. Seven mouse strains exhibited
      different levels of anxiety-like behaviors in the MC, and differential
      sensitivity to panel and light conditions. DBA/2J mice appeared most sensitive to
      the mirrored, versus black or white, panels and were therefore used in
      pharmacological MC studies. The mGlu5 receptor antagonist MPEP significantly
      decreased anxiety-like behaviors, similar to an intermediate dose of the
      benzodiazepine diazepam. The benzodiazepines chlordiazepoxide and alprazolam and
      the 5HT(1A) partial agonist buspirone had no effects on anxiety-like behaviors in
      the MC. None of the MC effects of active test compounds were attributable to non
      specific/locomotor effects. The antidepressants fluoxetine and venlafaxine
      increased anxiety-like behaviors in the MC. By contrast, the anxiolytic-like
      effects of chlordiazepoxide, diazepam and MPEP were revealed in the EPM in
      C57Bl6/J mice. In conclusion, the EPM test exhibits superior predictive validity
      compared to the MC test, despite the sensitivity of the MC to mouse strain
      differences.

PMID- 20149824
TI  - A new thermal stimulation method for human psychophysical studies: pain intensity
      clamping.
AB  - A method for testing changes in pain sensitivity of human subjects over the
      course of prolonged thermal stimulation is introduced. It uses a Peltier-device
      based thermode to generate a thermal contact stimulus, an electronic visual
      analog scale to continuously record the pain intensity and a system that controls
      selected stimulus parameters (temperature or pulse timing) as a function of the
      pain intensity rating. The stimulus parameter that is modulated to clamp pain
      intensity near a desired setpoint serves as the response variable and is used to
      infer pain sensitivity. Advantages of the method are that it automatically finds
      the stimulus magnitude that elicits predetermined pain intensity, regardless of
      how sensitive or insensitive the subject is, and it allows prolonged stimulation,
      because it does not allow pain intensity to escalate to unacceptable levels due
      to progressive sensitization. The subject is blinded regarding experimental
      effects because average pain intensity remains constant regardless of
      sensitization or pharmacological interventions.

PMID- 20149825
TI  - Detecting and tracking tremor in spike trains using the rectangular model based
      extended Kalman smoother.
AB  - Tremor is one of the most disabling symptoms in patients with movement disorders
      such as Parkinson's disease (PD) and essential tremor (ET). Spike trains
      extracted from microelectrode recordings are used to study the relationship of
      tremor exhibited by neuronal signals to physical tremor as measured with
      electromyograms (EMG), gyroscopes, or accelerometers. We describe a new method
      for continuously tracking the instantaneous tremor frequency and amplitude in
      spike trains based on a new state-space model and the extended Kalman smoother.
      This method can be used to detect periods of statistically significant tremor in
      recordings with intermittent tremor.

PMID- 20149820
TI  - Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological
      theory.
AB  - Reductionist attempts to dissect complex mechanisms into simpler elements are
      necessary, but not sufficient for understanding how biological properties like
      reward emerge out of neuronal activity. Recent studies on intracranial self
      administration of neurochemicals (drugs) found that rats learn to self-administer
      various drugs into the mesolimbic dopamine structures-the posterior ventral
      tegmental area, medial shell nucleus accumbens and medial olfactory tubercle. In
      addition, studies found roles of non-dopaminergic mechanisms of the
      supramammillary, rostromedial tegmental and midbrain raphe nuclei in reward. To
      explain intracranial self-administration and related effects of various drug
      manipulations, I outlined a neurobiological theory claiming that there is an
      intrinsic central process that coordinates various selective functions (including
      perceptual, visceral, and reinforcement processes) into a global function of
      approach. Further, this coordinating process for approach arises from
      interactions between brain structures including those structures mentioned above
      and their closely linked regions: the medial prefrontal cortex, septal area,
      ventral pallidum, bed nucleus of stria terminalis, preoptic area, lateral
      hypothalamic areas, lateral habenula, periaqueductal gray, laterodorsal tegmental
      nucleus and parabrachical area.

PMID- 20149826
TI  - Biogenesis of tartrate-resistant acid phosphatase isoforms 5a and 5b in stably
      transfected MDA-MB-231 breast cancer epithelial cells.
AB  - Tartrate-resistant acid phosphatase, although encoded by a single gene, exists as
      two isoforms in human serum, TRAP 5a and 5b, differing in post-translational
      modifications such as proteolytic processing and kinetic properties including pH
      optimum and specific activity. The biogenetic relationship between the TRAP
      isoforms was assessed in a stably transfected breast cancer epithelial MDA-MB-231
      cell subline overexpressing 5a- and 5b-like TRAP isoforms intracellularly, with
      only the monomeric 5a-like isoform being secreted. As judged by
      immunolocalization and comparative N-glycan profiling by Con A lectin
      chromatography and glycanase analysis, the majority of the intracellular
      monomeric TRAP was destined for secretion, while a minor portion provided the
      putative precursor for the intracellular 5b-like isoform. Brefeldin A blocked
      secretion of 5a-like TRAP isoform as well as appearance of its putative
      intracellular precursor, and augmented the intracellular level of proteolytically
      processed 5b-like isoform, indicating a common early biosynthetic precursor for
      TRAP isoforms 5a and 5b. The cysteine proteinase inhibitor E64 partially blocked
      formation of the 5b-like isoform while augmenting the level of its putative
      monomeric precursor, but did not alter the levels of secreted TRAP or its
      intracellular precursor, suggesting that distinct precursors for secreted TRAP 5a
      and intracellular 5b-like isoform are segregated in the ER or Golgi prior to
      proteolytic processing. In conclusion, these data provide evidence that distinct
      monomeric TRAP populations are diverted early in the secretory pathway either
      giving rise to a secreted, monomeric 5a-like TRAP isoform or to an intracellular,
      proteolytically processed 5b-like TRAP isoform.

PMID- 20149827
TI  - Coherent diffractive imaging of biological samples at synchrotron and free
      electron laser facilities.
AB  - Coherent X-ray diffractive imaging (CXDI) is a new imaging technique that offers
      the potential to image non-crystalline materials to sub-nanometer resolutions.
      Here we review the progress in CXDI of biological samples at both synchrotron and
      free electron laser (FEL) sources. We outline the experimental design of a CXDI
      experiment and summarize the iterative phase retrieval techniques that are used
      to produce images from the measured diffraction patterns. We describe a selection
      of key experiments performed in bio-imaging with CXDI from synchrotron sources,
      and we discuss the proof-of-principle experiments performed at FLASH at DESY in
      Hamburg. Finally, we show through simulation that for realistic parameters of
      hard X-ray FELs a resolution of a few nanometers may be achieved for individual
      biological objects imaged with single pulses of FEL radiation. Furthermore, we
      revise how this resolution may be improved to the sub-nanometer range if we image
      multiple copies of samples with a reproducible structure.

PMID- 20149828
TI  - Miniature on-chip detection of unpurified methicillin-resistant Staphylococcus
      aureus (MRSA) DNA using real-time PCR.
AB  - This paper evaluates the ability to detect three forms of methicillin-resistant
      Staphylococcus aureus (MRSA) in a microfluidic system. The MRSA was prepared off
      chip by varying levels of sample preparation: one containing purified genomic
      DNA, another containing the supernatant of a crude preparation using simple
      reagents, and a third through boiled culture preparation without any additional
      reagents. Polydimethylsiloxane (PDMS) microfluidic chips were fabricated using
      soft lithography and then bonded to a 22mmx22mmx0.1mm glass cover slip. A lid
      fabricated in a similar manner was used during compression to prevent bubble
      formation and evaporation in the stationary well-based chip. A miniature thermal
      cycler based on a resistive heater and a small fan were used to cycle through
      desired temperatures for polymerase chain reaction and fluorescent intensity
      measurements were taken at each cycle. Each form of template provided positive
      results utilizing the developed micro-PCR system (verified with gel
      electrophoresis). A serial dilution of the purified genomic DNA provided a
      standard curve with an efficiency of 1.77. The lowest concentration that provided
      clear positive results came from a 3microL sample containing 11.2pg of DNA. The
      ability to detect MRSA in a sample having undergone minimal sample preparation is
      a necessary step in the development of a point-of-care detection system capable
      of identifying infectious organisms.

PMID- 20149829
TI  - Systemic siRNA delivery using biocompatible calcium phosphate nanoparticles.

PMID- 20149830
TI  - Sequential analysis by immunoprecipitation-MALDI-TOF: a novel method for
      detection and identification of alloantibody specificities.
AB  - Alloantibodies are known to influence transplant outcomes. Apart from human
      leukocyte antigens (HLA), non-HLA targets have been suggested to play a
      significant role, but little is known about their nature. Here, we present a
      novel method for identification and characterization of cell surface antigens
      bound by alloreactive antibodies. Our method consists of 2 consecutive steps:
      first, immunoprecipitation of cell surface proteins is carried out with serum
      and, second, matrix-assisted laser desorption/ionization-time-of-flight is used
      to fingerprint the precipitated cell-surface proteins. As an example, we
      performed immunoprecipitation with peripheral blood lymphocytes, which had been
      incubated with an alloreactive serum; immune complexes were coupled to protein-G
      beads and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis;
      differential protein fractions were then analyzed by matrix-assisted laser
      desorption/ionization-time-of-flight. The method was validated with serum as well
      as with plasmapheresis material, which contained antibodies of known HLA
      specificities, demonstrating its applicability for clinical use.

PMID- 20149831
TI  - Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B,
      and HLA-G-DRB1 haplotypes in families with recurrent miscarriage.
AB  - A 14-base pair (bp) long insertion (ins)/deletion (del) polymorphism in exon 8 in
      the 3'-untranslated region of the human leukocyte antigen (HLA)-G gene is
      suggested to affect transcription of the gene. Carriage of the G14bp ins is
      associated with low levels of soluble HLA-G and increases the risk of recurrent
      miscarriage (RM). Due to existence of strong linkage disequilibrium (LD) in the
      HLA region, the primary susceptibility genes for RM in the HLA-G region have not
      yet been identified. HLA-A, -B, -DRB1, and -G14bp polymorphisms were investigated
      in 29 Caucasian families with two or more siblings suffering unexplained RM.
      Strong positive LD was detected between the G14bp ins and HLA-A*01, -A*11, -A*31,
      -B*08, and DRB1*03, whereas strong negative LD was found between G14bp ins and
      HLA-A*02, -A*03, and -A*24. The frequency of haplotypes with HLA-G14bp ins
      inherited from the mother was significantly increased in probands with RM (p =
      0.05). The increased compatibility between probands and their mothers for
      maternal G14 ins positive haplotypes suggests that maternal-fetal compatibility
      for chromosomal segments adjacent to HLA-G locus is a risk factor for female
      offspring to experience RM in their later reproductive life.

PMID- 20149832
TI  - Myasthenia gravis and respiratory failure in a patient with schizophrenia.

PMID- 20149834
TI  - Functional inactivation of triosephosphate isomerase through phosphorylation
      during etoposide-induced apoptosis in HeLa cells: potential role of Cdk2.
AB  - Up-regulation of cyclin-dependent protein kinase 2 (Cdk2) activity has been
      suggested to be prerequisite for progression of apoptosis induced by various
      apoptotic stimuli. In this study, we applied a phospho-proteomic technique to
      screen target molecules of Cdk2 during etoposide-induced apoptosis. For this
      purpose, phosphoproteins from the cell lysates were enriched by using Fe3+-IMAC
      column chromatography and resolved on a high resolution 2D PAGE gel. We
      identified six phosphoproteins by the use of MALDI-TOF technique. The cellular
      levels of these phosphoproteins were markedly reduced in the presence of
      etoposide in HeLa cells transfected with dominant negative mutant construct of
      Cdk2. Among the six candidate phosphoproteins, human triosephosphate isomerase
      (TPI), a glycolytic enzyme, was found to be a direct substrate of Cdk2 during
      etoposide-induced apoptosis. In an in vitro phosphorylation assay, TPI purified
      by use of a baculoviral expression system was phosphorylated by recombinant
      Cyclin A/Cdk2 kinase. This led to reduced enzyme activity for the conversion of
      glucose aldehyde-3-phosphate to dihydroxyacetone phosphate. Such phosphorylation
      of TPI and a subsequent decrease in its enzyme activity were prevented by
      treatment with olomoucine, a specific inhibitor of Cdk2. The above findings,
      taken together, suggest TPI as a potential target protein of Cyclin A/Cdk2. Loss
      of catalytic activity of TPI as a consequence of phosphorylation of this
      glycolytic enzyme may disrupt energy production in etoposide-treated HeLa cells,
      rendering these cells prone to undergo apoptosis.

PMID- 20149833
TI  - Echinacea purpurea extracts modulate murine dendritic cell fate and function.
AB  - Echinacea is a top-selling herbal remedy that purportedly acts as an
      immunostimulant. However, the specific immunomodulatory effects of Echinacea
      remain to be elucidated. We focused on defining the effects of Echinacea purpurea
      extracts in dendritic cells (DCs), which generate innate and adaptive immune
      responses. We hypothesized that E. purpurea extracts would enhance murine bone
      marrow-derived DC (BMDC) activation leading to increased immune responses. The
      fate and function of DCs from C57Bl/6 mice was evaluated following 48h exposure
      to E. purpurea root and leaf extracts. Flow cytometry revealed that the
      polysaccharide-rich root extract increased the expression of MHC class II, CD86,
      and CD54 surface biomarkers whereas the alkylamide-rich leaf extract inhibited
      expression of these molecules. Production of IL-6 and TNF-alpha increased in a
      concentration-dependent manner with exposure to the root, but not leaf, extract.
      In contrast, the leaf but not root extract inhibited the enzymatic activity of
      cyclooxygenase-2. While both extracts decreased the uptake of ovalbumin by BMDCs,
      the leaf but not root extract inhibited the antigen-specific activation of naive
      CD4(+) T cells from OT II/Thy1.1 mice. Collectively, these results suggest that
      E. purpurea can be immunostimulatory, immunosuppressive, and/or anti-inflammatory
      depending on the portion of the plant and extraction method.

PMID- 20149835
TI  - Attenuation of oxidative stress and inflammation by gravinol in high glucose
      exposed renal tubular epithelial cells.
AB  - Gravinol, a proanthocyanidin from grape seeds, has polyphenolic properties with
      powerful anti-oxidative effects. Although, increasing evidence strongly suggests
      that polyphenolic antioxidants suppress diabetic nephropathy that is causally
      associated with oxidative stress and inflammation, gravinol's protective action
      against diabetic nephropathy has not been fully explored to date. In the current
      study, we investigated the protective action of gravinol against oxidative stress
      and inflammation using the experimental diabetic nephropathy cell model, high
      glucose-exposed renal tubular epithelial cells. To elucidate the underlying
      actions of gravinol, several oxidative and inflammatory markers were estimated.
      Included are measurements of lipid peroxidation, total reactive species (RS),
      superoxide (O(2)), nitric oxide (NO), and peroxynitrite (ONOO(-)), as well as
      nuclear factor-kappa B (NF-kappaB) nuclear translocation. Results indicate that
      gravinol had a potent inhibitory action against lipid peroxidation, total RS,
      O(2), NO, ONOO(-), the reduced glutathione (GSH)/oxidized glutathione (GSSG)
      ratio and more importantly, against NF-kappaB nuclear translocation. We propose
      that gravinol's strong protective effect against high glucose-induced renal
      tubular epithelial cell damage attenuates diabetic nephropathy by suppressing
      oxidative stress and inflammation.

PMID- 20149836
TI  - Neuronal models for evaluation of proliferation in vitro using high content
      screening.
AB  - In vitro test methods can provide a rapid approach for the screening of large
      numbers of chemicals for their potential to produce toxicity (hazard
      identification). In order to identify potential developmental neurotoxicants, a
      battery of in vitro tests for neurodevelopmental processes such as cell
      proliferation, differentiation, growth, and synaptogenesis has been proposed. The
      development of in vitro approaches for toxicity testing will require choosing a
      model system that is appropriate to the endpoint of concern. This study compared
      several cell lines as models for neuronal proliferation. The sensitivities of
      neuronal cell lines derived from three species (PC12, rat; N1E-115, mouse; SH
      SY5Y, human) to chemicals known to affect cell proliferation were assessed using
      a high content screening system. After optimizing conditions for cell growth in
      96-well plates, proliferation was measured as the incorporation of 5-bromo-2'
      deoxyuridine (BrdU) into replicating DNA during S phase. BrdU-labeled cells were
      detected by immunocytochemistry and cell counts were obtained using automated
      image acquisition and analysis. The three cell lines showed approximately 30-40%
      of the population in S phase after a 4h pulse of BrdU. Exposure to the DNA
      polymerase inhibitor aphidicolin for 20 h prior to the 4h pulse of BrdU
      significantly decreased proliferation in all three cell lines. The sensitivities
      of the cell lines were compared by exposure to eight chemicals known to affect
      proliferation (positive controls) and determination of the concentration
      inhibiting proliferation by 50% of control (I(50)). PC12 cells were the most
      sensitive to chemicals; 6 out of 8 chemicals (aphidicolin, cadmium, cytosine
      arabinoside, dexamethasone, 5-fluorouracil, and methylmercury) inhibited
      proliferation at the concentrations tested. SH-SY5Y cells were somewhat less
      sensitive to chemical effects, with five out of eight chemicals inhibiting
      proliferation; dexamethasone had no effect, and cadmium inhibited proliferation
      only at concentrations that decreased cell viability. Data from the N1E-115 cell
      line was extremely variable between experiments, and only 4 out of 8 chemicals
      resulted in inhibition of proliferation. Chemicals that had not been previously
      shown to alter proliferation (negative controls) did not affect proliferation or
      cell viability in any cell line. The results show that high content screening can
      be used to rapidly assess chemical effects on proliferation. Three neuronal cell
      lines exhibited differential sensitivity to the effect of chemicals on this
      endpoint, with PC12 cells being the most sensitive to inhibition of
      proliferation.

PMID- 20149837
TI  - The biopsychology of emotion: current theoretical, empirical, and methodological
      perspectives.

PMID- 20149838
TI  - Modelling simultaneous echo waveform reconstruction and localization in bats.
AB  - Echolocating bats perceive the world through sound signals reflecting from the
      objects around them. In these signals, information is contained about reflector
      location and reflector identity. Bats are able to extract and separate the cues
      for location from those that carry identification information. We propose a model
      based on Wiener deconvolution that also performs this separation for a virtual
      system mimicking the echolocation system of the lesser spearnosed bat,
      Phyllostomus discolor. In particular, the model simultaneously reconstructs the
      reflected echo signal and localizes the reflector from which the echo originates.
      The proposed technique is based on a model that performs a similar task based on
      information from the frog's lateral line system. We show that direct application
      of the frog model to the bat sonar system is not feasible. However, we suggest a
      technique that does apply to the bat biosonar and indicate its performance in the
      presence of noise.

PMID- 20149839
TI  - Simulation of neurocomputing based on the photophobic reactions of Euglena with
      optical feedback stimulation.
AB  - To explore possible forms of unconventional computers that have high capacities
      for adaptation and exploration, we propose a new approach to developing a
      biocomputer based on the photophobic reactions of microbes (Euglena gracilis),
      and perform the Monte-Carlo simulation of Euglena-based neural network computing,
      involving virtual optical feedback to the Euglena cells. The photophobic
      reactions of Euglena are obtained experimentally, and incorporated in the
      simulation, together with a feedback algorithm with a modified Hopfield-Tank
      model for solving a 4-city traveling salesman problem. The simulation shows high
      performances in terms of (1) reaching one of the best solutions of the problem,
      and (2) searching for a number of solutions via dynamic transition among the
      solutions. This dynamic transition is attributed to the fluctuation of state
      variables, global oscillation through feedback instability, and the one-by-one
      change of state variables.

PMID- 20149840
TI  - Fasting induces a high level of 3-nitrotyrosine in the brain of rats.
AB  - Although the relationship between hyperglycemia (using diabetic animal model) and
      plasma nitrotyrosine level has been studied, the effect of hypoglycemia on
      nitrotyrosine level in the brain has not been addressed. Here, we evaluated
      nitration of protein, the colocalization of nitration with alpha-synuclein,
      activity of inducible nitric oxide synthase, and nitric oxide content using
      fasting and diabetic animal models. The results showed that signals of alpha
      synuclein were widely distributed in most parts of the pallium, midbrain,
      hippocampus and cerebellum, as indicated by immunohistochemistry. Most signals of
      the 3-nitrotyrosine were colocalized with those of alpha-synuclein in the
      midbrain of fasting rats. The level of proteins containing 3-nitrotyrosine was
      significantly increased in the brain of fasting rats in Western blotting,
      especially in the midbrain, compared with control rats. In addition, the 3
      nitrotyrosine signals increased in hippocampus of diabetic rats.
      Immunoprecipitation showed that alpha-synuclein was nitrated in the fasting rats.
      The iNOS activity and nitric oxide levels were significantly increased in both
      fasting and diabetic animals. The enhanced 3-nitrotyrosine level in the brain of
      fasting rats suggests that nitration of protein including alpha-synuclein in the
      midbrain is more affected by hypoglycemia in fasting than hyperglycemia in
      diabetic rats.

PMID- 20149841
TI  - Neonatal bladder inflammation alters activity of adult rat spinal visceral
      nociceptive neurons.
AB  - PURPOSE: This investigation examined the effect of inflammation produced by
      intravesical zymosan during the neonatal period on spinal dorsal horn neuronal
      responses to urinary bladder distension (UBD) as adults. METHODS: Female rat pups
      (P14-P16) were treated with intravesical zymosan or with anesthesia-only. These
      groups of rats were subdivided forming four groups: half received intravesical
      zymosan as adults and half received anesthesia-only. One day later, rats were
      anesthetized, the spinal cord was transected at a cervical level and
      extracellular single-unit recordings of L6-S1 dorsal horn neurons were obtained.
      Neurons were classified as Type I--inhibited by heterotopic noxious conditioning
      stimuli (HNCS) or as Type II--not inhibited by HNCS--and were characterized for
      Spontaneous Activity and responses to graded UBD (20-60 mm Hg). RESULTS: 227
      spinal dorsal horn neurons excited by UBD were characterized. In rats treated as
      neonates with anesthesia-only, Type II neurons demonstrated increased spontaneous
      and UBD-evoked activity following adult intravesical zymosan treatment whereas
      Type I neurons demonstrated decreased spontaneous and UBD-evoked activity
      relative to controls. In rats treated as neonates with intravesical zymosan, the
      spontaneous and UBD-evoked activity of both Type I and Type II neurons increased
      following adult intravesical zymosan treatment relative to controls. CONCLUSIONS:
      Neonatal bladder inflammation alters subsequent effects of acute bladder
      inflammation on spinal dorsal horn neurons excited by UBD such that overall there
      is greater sensory neuron activation. This may explain the visceral
      hypersensitivity noted in this model system and suggest that impaired inhibitory
      systems may be responsible.

PMID- 20149842
TI  - Astrocytic activation in thoracic spinal cord contributes to persistent pain in
      rat model of chronic pancreatitis.
AB  - One of the most important symptoms in chronic pancreatitis (CP) is constant and
      recurrent abdominal pain. However, there is still no ideal explanation and
      treatment on it. Previous studies indicated that pain in CP shared many
      characteristics of neuropathic pain. As an important mechanism underlying
      neuropathic pain, astrocytic activation is probably involved in pain of CP. Based
      on the trinitrobenzene sulfonic acid (TNBS)-induce rat CP model, we performed
      pancreatic histology to assess the severity of CP with semiquantitative scores
      and tested the nociceptive behaviors following induction of CP. Glial fibrillary
      acidic protein (GFAP) expressions in the thoracic spinal cord were observed by
      immunohistochemistry and real-time reverse transcription polymerase chain
      reaction (RT-PCR). Meanwhile, we injected intrathecally astrocytic specific
      inhibitor l-alpha-aminoadipate (LAA) and observed its effect on nociception
      induced by CP. Compared to the naive and sham group, TNBS produced long lasting
      pancreatitis, and persistent mechanical hypersensitivity in the abdomen that was
      evident 1 week after TNBS infusion and persisted up to 5 weeks. Compared with
      naive or sham operated rats, GFAP staining was significantly increased 5 weeks
      after CP induction. Real-time RT-PCR indicated that GFAP expression was
      significantly increased in TNBS treated rats compared to the sham group. TNBS
      induced astrocytic activation was significantly attenuated by LAA, compared with
      the saline control. Treatment with LAA significantly, even though not completely,
      attenuated the allodynia. Our results provide for the first time that astrocytes
      may play a critical role in pain of CP. Some actions could be taken to prevent
      astrocytic activation to treat pain in CP patients.

PMID- 20149843
TI  - Hydrogen sulfide protects neurons against hypoxic injury via stimulation of ATP
      sensitive potassium channel/protein kinase C/extracellular signal-regulated
      kinase/heat shock protein 90 pathway.
AB  - Cerebral hypoxia is one of the main causes of cerebral injury. This study was
      conducted to investigate the potential protective effect of H(2)S in in vitro
      hypoxic models by subjecting SH-SY5Y cells to either oxygen-glucose deprivation
      or Na(2)S(2)O(4) (an oxygen scavenger) treatment. We found that treatment with
      NaHS (an H(2)S donor, 10-100 microM) 15 min prior to hypoxia increased cell
      viability in a concentration-dependent manner. Time-course study showed that NaHS
      was able to exert its protective effect even when added 8 h before or less than 4
      h after hypoxia induction. Interestingly, endogenous H(2)S level was markedly
      reduced by hypoxia induction. Over-expression of cystathionine-beta-synthase
      prevented hypoxia induced cell apoptosis. Blockade of ATP-sensitive K(+) (K(ATP))
      channels with glibenclamide and HMR-1098, protein kinase C (PKC) with its three
      specific inhibitors (chelerythrine, bisindolylmaleide I and calphostin C),
      extracellular signal-regulated kinase 1/2 (ERK1/2) with PD98059 and heat shock
      protein 90 (Hsp90) with geldanamycin and radicicol significantly attenuated the
      protective effects of NaHS. Western blots showed that NaHS significantly
      stimulated ERK1/2 activation and Hsp90 expression. In conclusion, H(2)S exerts a
      protective effect against cerebral hypoxia induced neuronal cell death via
      K(ATP)/PKC/ERK1/2/Hsp90 pathway. Our findings emphasize the important
      neuroprotective role of H(2)S in the brain during cerebral hypoxia.

PMID- 20149844
TI  - Compensation aids skilled reaching in aging and in recovery from forelimb motor
      cortex stroke in the rat.
AB  - Compensatory movements mediate success in skilled reaching for food after stroke
      to the forelimb region of motor cortex (MtCx) in the rat. The present study asks
      whether the neural plasticity that enables compensation after motor stroke is
      preserved in aging. In order to avoid potential confounding effects of age
      related negative-learning, rats were trained in a single pellet reaching task
      during young-adulthood. Subgroups were retested before and after contralateral
      forelimb MtCx stroke via pial stripping given at 3, 18, or 23 months of age. Over
      a two-month post-stroke rehabilitation period, end point measures were made of
      learned nonuse, recovery, retention, and performance ratings were made of
      reaching movement elements. Prior to stroke, young and aged rats maintained
      equivalent end point performance but older rats displayed compensatory changes in
      limb use as measured with ratings of the elements of forelimb movement. Following
      stroke, the aged groups of rats were more impaired on end point, movement, and
      anatomical measures. Nevertheless, the aged rats displayed substantial recovery
      via the use of compensatory movements. Thus, this study demonstrates that the
      neural plasticity that mediates compensatory movements after stroke in young
      adults is preserved prior to and following stroke in aging.

PMID- 20149845
TI  - The role of dopamine in maintenance and distractability of attention in the
      "prefrontal cortex" of pigeons.
AB  - Selective attention is a crucial component of all sensory processing. Here we
      test the role of dopamine in attentional selection and in the maintenance of
      attention. Pigeons were trained on a moving-dot paradigm comparable to the shell
      game. In this paradigm, pigeons had to select a target among distractors and
      maintain attention to the target. Target and distractors consisted of white dots,
      moving at random on a touch-screen. In this task, the demand on attention was
      modulated by varying the number of distractors and the duration of motion. Both
      manipulations affected performance equally. In the next step, we investigated the
      contribution of dopamine to attention. Intracranial injections of D1-antagonist
      (Sch23390) before testing led to decrements in performance that equally affected
      trials with different attentional demand. This drop in performance cannot be
      attributed to altered motivation or motor performance. We conclude that dopamine
      has a critical role in attention. It is involved in the selection of targets for
      attention and in the stabilization of attention against interference. This is
      comparable to the role dopamine plays in working memory and argues for similar
      mechanisms underlying selective attention and working memory.

PMID- 20149846
TI  - Somatostatin selectively ablates post-inspiratory activity after injection into
      the Botzinger complex.
AB  - Somatostatin (SST) neurons in the ventral respiratory column (VRC) are essential
      for the generation of normal breathing. Little is known about the neuromodulatory
      role of SST on ventral respiratory neurons other than that local administration
      induces apnoea. Here, we describe the cardiorespiratory effects of microinjecting
      SST into the preBotzinger and Botzinger complexes which together elaborate a
      normal inspiratory augmenting and expiratory respiratory pattern, and on spinally
      projecting respiratory subnuclei (rostral ventral respiratory group; rVRG).
      Microinjections (20-50 nl) of SST (0.15, 0.45, 1.5 mM) were made into respiratory
      subnuclei of urethane-anaesthetized, paralysed, vagotomized and artificially
      ventilated Sprague-Dawley rats (n=46). Unilateral microinjection of SST into the
      Botzinger complex converted the augmenting activity of phrenic nerve discharge
      into a square-wave apneustic pattern associated with a lengthening of inspiratory
      period and shortening of expiratory time. Following bilateral microinjection the
      apneusis became pronounced and was associated with a dramatic variability in
      inspiratory duration. Microinjection of SST into the Botzinger complex also
      abolished the post-inspiratory (post-I) motor activity normally observed in vagal
      and sympathetic nerves. In the preBotzinger complex SST caused bradypnoea and
      with increasing dose, apnoea. In the rVRG SST reduced phrenic nerve amplitude,
      eventually causing apnoea. In conclusion, SST powerfully inhibits respiratory
      neurons throughout the VRC. Of particular interest is the finding that chemical
      inhibition of the Botzinger complex with SST ablates the post-I activity that is
      normally seen in respiratory activity and leads to apneusis. This loss of post-I
      activity is a unique feature of inhibition with SST and is not seen following
      inhibition with other agents such as galanin, GABA and endomorphin. The effect
      seen on post-I activity is similar to the effect of inhibiting the Kolliker-Fuse
      nucleus in the pons. The mechanism by which SST exerts this effect on Botzinger
      neurons remains to be determined.

PMID- 20149847
TI  - The role of orexin-A in food motivation, reward-based feeding behavior and food
      induced neuronal activation in rats.
AB  - Consumption beyond homeostatic needs, referred to here as reward-based feeding
      behavior, is a central contributor to the current obesity epidemic worldwide.
      Importantly, reward-based feeding can be driven by palatability, the taste and
      texture of the food, as well as cues associated with the consumption of palatable
      foods. The hypothalamic orexin system regulates both diet preference and
      anticipation of food rewards making it a likely target to modulate reward-based
      feeding behavior. In the current manuscript we hypothesized that orexin signaling
      mediates food-motivated behaviors and reward-based feeding behavior. We further
      hypothesized that orexin neurons and targets of the orexin system become
      activated in response to cues associated with the consumption of palatable food.
      Data from these studies suggest that orexin signaling promotes progressive ratio
      responding for palatable foods while blockade of orexin signaling attenuates
      reward-based feeding of a high fat diet. In addition, cues linked to the
      consumption of chocolate, or the receipt of a daily meal, activate the orexin
      system and its target regions differentially. Collectively, these data suggest
      that orexin signaling mediates reward-based feeding behavior and, within specific
      target regions, may regulate cue-induced overconsumption of palatable foods.

PMID- 20149848
TI  - Time course quantification of spastic hypertonia following spinal hemisection in
      rats.
AB  - Progressive changes in the muscle tone and stretch reflex after spinal cord
      injury (SCI) provide insight into the time-course development of spasticity. This
      study quantified the time-course changes of hypertonia for rats following SCI of
      T8 hemisection. A miniature manual stretching device measured the reactive torque
      via a pair of pressure sensing balloons; the angular displacement was measured
      via an optoelectronic device. Various stretching frequencies were tested,
      specifically 1/3, 1/2, 1, 3/2 and 2 Hz. The reactive torque and angular
      displacement were used to derive the viscous and elastic components representing
      the viscosity and stiffness of the rat's ankle joint. The enhanced velocity
      dependent properties of spasticity were observed in the SCI hemisection rats
      (n=9) but not in the controls (n=9). Time-course measurements from pre-surgery to
      56 days following SCI showed that the muscle tone of the hemisection rats dropped
      immediately after spinal shock and then gradually increased to reach a peak
      around 21 days postinjury (P<0.01). The muscle tone remained at least 75% of the
      peak value up to the end of an 8 week observation period (P<0.05). The changes of
      muscle tone can also be verified from the electrophysiological evaluations of
      electromyography (EMG) (P<0.05). In addition to conventional BBB motor behavior
      score, our results provided time-course quantification of the biomechanical and
      electrophysiological properties of muscle tone from the onset of SCI. Such data
      are useful for investigating progressive recovery of spinal damage in animal
      model and for future objective assessment of improved treatment for SCI human
      subjects.

PMID- 20149849
TI  - Neurofunctional markers of successful dieting.

PMID- 20149851
TI  - In vitro TAXOL production, by Pestalotiopsis breviseta--a first report.
AB  - Coelomycetous fungi were screened for the production of TAXOL. TAXOL production
      of Pestalotiopsis breviseta fungi is confirmed by Ultra Violet (UV) spectroscopic
      analysis, Infra Red (IR) analysis, high performance liquid chromatography (HPLC),
      nuclear magnetic resonance (NMR) and LC-MASS spectroscopy. TAXOL isolated from
      the P. breviseta fungus was identical with authentic TAXOL and produces 0.064
      mg/L (0.128% dry weight of fungal mat).

PMID- 20149852
TI  - Vectors for co-expression of two genes in Caenorhabditis elegans.
AB  - To meet the increasing need of simultaneously co-expressing two different genes
      in the same cell of transgenic Caenorhabditis elegans, here, we report the
      establishment of dicistronic vectors that contain an intercistronic region (ICR)
      of the C. elegans operon, CEOP5428. In these vectors, a green fluorescence
      protein (GFP) and a red FP (RFP) genes were placed in the first and second
      cistrons, respectively, which were separated by the ICR. Driven by the
      fibrillarin (fib-1) or myo-2 promoter, the GFP- and RFP-fusion proteins were
      consistently co-expressed in the entire worm cells or in the pharynx muscle cells
      of the transgenic worms, respectively. Our work demonstrates that ICR-containing
      dicistronic vectors could be developed into versatile co-expression systems in C.
      elegans for functional analysis of genes of interest.

PMID- 20149853
TI  - In vitro drug release mechanism from lipid nanocapsules (LNC).
AB  - Lipid nanocapsules are recently developed lipid nanocarriers for delivery of
      lipophilic drugs. Due to their small size and biocompatible nature, lipid
      nanocapsules (LNC) may be promising carriers for drug delivery with different
      routes of administration. The aim of this work was to study the effect of
      formulation variables on the in vitro drug release from LNC. Ibuprofen as a model
      drug was entrapped in the oily core while Cremophor A25 and Cremophor A6 were
      used as hydrophilic surfactants in different ratios ranging from 1:1 to 1:0. All
      the prepared LNC were of comparable particle sizes around 50nm. Varying Cremophor
      compositions as well as the presence of lecithin, cetyl or stearyl alcohol had no
      significant effect on the in vitro drug release profiles. However, drug release
      rates increased significantly with increasing the temperature from 4 to 50
      degrees C, i.e. the flux increased from 1.5 to 7microg/(cm(2)min). This was
      explained by the increased ibuprofen-lipid interactions at reduced temperature
      where the increased viscosity of the lipid significantly slows down the drug
      diffusion to the external aqueous phase. In summary, the physicochemical
      properties of the drug as well as the oil phase have a high impact on the drug
      release rate while the surfactant type, composition or density exerted only a
      minor effect.

PMID- 20149855
TI  - Citrus limetta leaves extract antagonizes the hypertensive effect of angiotensin
      II.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Citrus limetta Risso (Rutaceae) is widely used in
      Mexico for healing purposes, among them as antihypertensive treatment. AIM OF THE
      STUDY: To assess the antihypertensive effect of C. limetta leaves as one of its
      ethnomedical uses. MATERIALS AND METHODS: The acute response of blood pressure to
      angiotensin II administration was measured in mice. Additionally, the acute oral
      toxicity profiles were determined. RESULTS: The findings of the current
      investigation showed that different concentrations of the aqueous extract
      prevented the raise of systolic blood pressure (p< or =0.001 vs. vehicle),
      diastolic blood pressure (p< or =0.0002 vs. vehicle) and mean blood pressure (p<
      or =0.0000 vs. vehicle); with a dose dependent effect for diastolic pressures at
      125-500mg/kg dosages. The 500 and 1000mg/kg doses inhibited the action of Ang II
      in similar extent to telmisartan. Toxic signs or deaths were not observed in mice
      treated at 2000mg/kg of C. limetta extract. CONCLUSIONS: All doses of C. limetta
      aqueous extract, used in this assay, were safe and effective.

PMID- 20149854
TI  - Mechanics of the frog ear.
AB  - The frog inner ear contains three regions that are sensitive to airborne sound
      and which are functionally distinct. (1) The responses of nerve fibres
      innervating the low-frequency, rostral part of the amphibian papilla (AP) are
      complex. Electrical tuning of hair cells presumably contributes to the frequency
      selectivity of these responses. (2) The caudal part of the AP covers the mid
      frequency portion of the frog's auditory range. It shares the ability to generate
      both evoked and spontaneous otoacoustic emissions with the mammalian cochlea and
      other vertebrate ears. (3) The basilar papilla functions mainly as a single
      auditory filter. Its simple anatomy and function provide a model system for
      testing hypotheses concerning emission generation. Group delays of stimulus
      frequency otoacoustic emissions (SFOAEs) from the basilar papilla are accounted
      for by assuming that they result from forward and reverse transmission through
      the middle ear, a mechanical delay due to tectorial membrane filtering and a
      rapid forward and reverse propagation through the inner ear fluids, with
      negligible delay.

PMID- 20149856
TI  - Identification of rosmarinic acid as the major active constituent in Cordia
      americana.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Preparation from leaves of Cordia americana have
      been widely used in traditional medicine in South Brazil to treat wounds and
      various inflammations. AIM OF THE STUDY: The objective of this work was to
      identify the effective compounds in the ethanolic extract prepared from the
      leaves of Cordia americana, which is used in traditional South Brazilian medicine
      as anti-inflammatory and wound healing remedy. MATERIALS AND METHODS: Isolation
      and structure elucidation techniques were performed in order to identify the
      compounds of Cordia americana and HPLC analysis was used for the quantification.
      The major constituent and the ethanolic extract were investigated for inhibition
      of 5-lipoxygenase, p38alpha MAPK, TNFalpha release and NF-kappaB as well as in
      the fibroblast scratch assay. RESULTS: Rosmarinic acid (1) was identified as the
      major compound with an amount of 8.44% in the ethanolic extract of the leaves of
      Cordia americana. The ethanolic extract as well as (1) exhibited the highest
      inhibitory effects on 5-lipoxygenase (IC(50)=0.69 and 0.97microg/mL, resp., IC50
      of BWA4C as reference: 0.3microM) and p38alpha (IC50=3.25 and 1.16microg/mL,
      resp., IC50 of SB203580 as reference: 0.046microM) and moderate inhibitory
      effects on TNFalpha release. Slight effects were observed in the fibroblast
      scratch assay. CONCLUSIONS: This study increases our knowledge on the effective
      compound in Cordia americana and supports its use in traditional medicine. We
      demonstrated for the first time pharmacological effects of Cordia americana and
      we provide evidences for a crucial role of rosmarinic acid as the major key
      player.

PMID- 20149857
TI  - Using soil bacteria to facilitate phytoremediation.
AB  - In the past twenty years or so, researchers have endeavored to utilize plants to
      facilitate the removal of both organic and inorganic contaminants from the
      environment, especially from soil. These phytoremediation approaches have come a
      long way in a short time. However, the majority of this work has been done under
      more controlled laboratory conditions and not in the field. As an adjunct to
      various phytoremediation strategies and as part of an effort to make this
      technology more efficacious, a number of scientists have begun to explore the
      possibility of using various soil bacteria together with plants. These bacteria
      include biodegradative bacteria, plant growth-promoting bacteria and bacteria
      that facilitate phytoremediation by other means. An overview of bacterially
      assisted phytoremediation is provided here for both organic and metallic
      contaminants, with the intent of providing some insight into how these bacteria
      aid phytoremediation so that future field studies might be facilitated.

PMID- 20149858
TI  - MG132, a proteasome inhibitor decreased the growth of Calu-6 lung cancer cells
      via apoptosis and GSH depletion.
AB  - The inhibition of proteasome function has emerged as a useful strategy to
      maneuver apoptosis. In the present study, we evaluated the effects of MG132 as a
      proteasome inhibitor on the growth of Calu-6 lung cancer cells in relation to the
      cell cycle, cell death, reactive oxygen species (ROS) and glutathione (GSH)
      levels. MG132 dose-dependently inhibited the growth of Calu-6 cells at 24h. DNA
      flow cytometric analysis indicated that 1-30 microM MG132 induced an S phase
      arrest in Calu-6 cells. MG132 also induced apoptosis, which was accompanied by
      the loss of mitochondrial membrane potential (MMP; Deltapsi(m)). The pan-caspase
      inhibitor (Z-VAD) significantly rescued Calu-6 cells from MG132-induced cell
      death. The intracellular ROS levels including O(2)(-) were increased in MG132
      treated Calu-6 cells. MG132 also increased GSH-depleted cell numbers in Calu-6
      cells. Z-VAD significantly decreased O(2)(-) levels and GSH-depleted cell numbers
      in MG132-treated Calu-6 cells. In conclusion, MG132 inhibited the growth of Calu
      6 cells via apoptosis and GSH depletion.

PMID- 20149859
TI  - Membrane-impermeable estrogen is involved in regulation of calbindin-D9k
      expression via non-genomic pathways in a rat pituitary cell line, GH3 cells.
AB  - Estrogen (E2) has been shown to regulate various functions for many pituitary
      hormones. Recently, the potential roles of non-genomic pathways in E2-induced
      actions have been proposed in the previous studies, however, the effects of E2
      remain to be elucidated in regard to non-genomic induction of cytosolic protein
      calbindin-D9k (CaBP-9k). To gain a better understanding of the molecular events
      underlying E2-induced expression of CaBP-9k, rat pituitary tumor cells (GH3
      cells) were treated with E-BSA (membrane impermeable E2-conjugated with BSA). Non
      genomic induction of CaBP-9k by E-BSA was determined using RT-PCR and western
      blot analysis. The significant increase in CaBP-9k mRNA level was observed as
      early as 15 min following treatment with a high concentration of E-BSA (10(-6)M),
      whereas rapid and significant induction of CaBP-9k protein was noted at 5, 15 and
      30 min after E-BSA exposure (p<0.05). In order to determine the potential
      involvement of different signaling pathways, several inhibitors were employed,
      i.e., ICI 182,780 for the estrogen receptor (ER) pathway, pertussis toxin (PTX)
      for the G-protein-coupled signaling pathway, U0126 (U) for the ERK (extracellular
      regulated kinase) and wortmannin (W) for the Akt (protein kinase B). Co-treatment
      with ICI 182, 780 and PTX reversed an E-BSA-induced increase in CaBP-9k mRNA and
      protein. Although neither U nor W alone attenuated E-BSA-induced effects, these
      inhibitors together abolished E-BSA-induced CaBP-9k expression, suggesting their
      involvement in its regulation. Taken together, these results demonstrate the
      involvement of various signaling pathways in E2-induced regulation of CaBP-9k. In
      addition, ER and G-protein-coupled signaling pathways may play central roles in
      the non-genomic activities of E2 and that downstream signaling via ERK and Akt
      are required to evoke ER-mediated induction of CaBP-9k in vitro.

PMID- 20149860
TI  - In vitro and in vivo haemolytic studies of tentacle-only extract from jellyfish
      Cyanea capillata.
AB  - To approach the real haemolytic process of jellyfish toxins, both in vitro and in
      vivo haemolysis of tentacle-only extract (TOE) from jellyfish Cyanea capillata
      has been studied. Dose-response curves of the haemolytic activity of TOE in vitro
      were sigmoid shaped in both erythrocyte suspension and diluted whole blood, with
      the former more sensitive to TOE. The in vivo haemolysis increased sharply in the
      first 10 min and was followed by a gradual increase in the following 3h, with
      increasing blood potassium and lactic acid accordingly. SC5b-9 complexes were
      significantly up-regulated in vitro, but not in vivo. These results showed that
      the haemolysis of TOE in diluted whole blood and in vivo is not totally
      consistent with that in the erythrocyte suspension, and blood plasma might play a
      protective role against haemolysis. Thus we suggested that erythrocyte suspension
      can be used to test the damage of toxin on erythrocyte membrane, while the
      diluted whole blood may be more suitable to test the haemolysis of toxins.

PMID- 20149861
TI  - Antioxidant and antimutagenic activity of Carum copticum fruit extracts.
AB  - The ajowain (Carum copticum (L.)) is a popular spice and traditionally used in
      Indian system of medicine. Considering the importance of natural products in
      modern phytomedicine, the antioxidant and antimutagenic activities of C. copticum
      fruits extract and its fractions were evaluated. The methanol fraction showed
      highest antioxidant activity by phosphomolybdenum (2087.7 micromol) and DPPH
      assay (90.2%) followed by other fractions comparable to ascorbic acid and BHT.
      Based on antioxidant activity, methanol fraction was evaluated for antimutagenic
      potential against direct acting mutagens sodium azide (NaN(3)) and methyl methane
      sulphonate (MMS) and indirect acting mutagens 2-aminofluorene (2-AF) and
      benzo(a)pyrene (B(a)P), using Salmonella typhimurium (TA97a, TA98, TA100, and
      TA102) tester strains. The methanolic fraction showed no sign of mutagenicity at
      tested concentrations (25-100 microg/plate). Antimutagenic activity was recorded
      with inhibition of mutagenicity ranging from 10.8% to 83.1% in a concentration
      dependent manner. The phytochemical analysis by IR, HPLC, GC-MS, and total
      phenolic assay revealed a high content of phenolic terpenoids. Further,
      characterization of active principle is needed to understand the mechanism of
      action and therapeutic efficacy in vivo.

PMID- 20149862
TI  - Differential abilities of the mushroom ribosome-inactivating proteins hypsin and
      velutin to perturb normal development of cultured mouse embryos.
AB  - The teratogenicity of two fungal ribosome-inactivating proteins, hypsin from
      Hypsizigus mamoreus and velutin from Flammulina velutipes, was examined in this
      investigation using microinjection and postimplantation whole-embryo culture. The
      results demonstrated that hypsin induced abnormal embryonic development at 2.5
      microM during the organogenesis period from E8.5 to E9.5. As its dosage
      increased, there was an increase in the total number of abnormal embryos, a drop
      in the final somite number, and a rise of abnormal structures. Structural
      abnormalities were detected: open cranial neural tube, abnormal branchial arches,
      absence of forelimb buds and twisted body axis. The otic and optic placodes were,
      however, less affected. Histological study of the abnormal embryos revealed a
      correlation of increased cell death with abnormal structures, suggesting that
      induction of cell death by hypsin may account for its teratogenicity. In
      contrast, velutin did not exert any adverse influence on mouse development.

PMID- 20149863
TI  - A fluorescent investigation of subcellular damage in H9c2 cells caused by
      pavetamine, a novel polyamine.
AB  - Gousiekte, which can be translated literally as "quick disease", is one of the
      six most important plant toxicoses that affect livestock in South Africa. It is a
      plant-induced cardiomyopathy of domestic ruminants characterised by the sudden
      death of animals within a period of 4-8weeks after the initial ingestion of the
      toxic plant. The main ultrastructural change in sheep hearts is degradation of
      myofibres. In this study, fluorescent probes were used to investigate subcellular
      changes induced by pavetamine, the toxic compound that causes gousiekte, in H9c2
      cells. The sarcoplasmic reticula (SR) and mitochondria showed abnormalities that
      were not present in the control cells. The lysosomes of treated cells were more
      abundant and enlarged than those of the control cells. There was increased
      activity of cytosolic hexosaminidase and acid phosphatase, indicating increased
      lysosomal membrane permeability. Lysosomes play an important role in both
      necrosis and apoptosis. The degradation of the myofibres may be a consequence of
      the increased lysosomal membrane permeability. Pavetamine was also found to cause
      alterations in the organisation of F-actin. F-actin in the nucleus is a
      transcription regulator and can therefore influence protein synthesis. Actin
      filament organisation also regulates the cardiac L-type Ca(2+) channels.
      Fluorescent staining demonstrated that pavetamine may damage a number of
      organelles, all of which can influence the proper functioning of the heart.

PMID- 20149864
TI  - "Tissue-repairing" blood-derived macrophages are essential for healing of the
      injured spinal cord: from skin-activated macrophages to infiltrating blood
      derived cells?
AB  - Until recently, the local inflammation that occurs in response to spinal cord
      injury has received a negative reputation; overall, it was assumed to be one of
      the major causes of a vicious neurotoxic cycle that leads to impaired recovery
      following injury. This local inflammation involves both the activated tissue
      resident microglia and monocyte-derived macrophages infiltrating from the blood.
      Ten years ago, we proposed that the blood-derived macrophages, reminiscent of
      "alternatively activated" macrophages (also known as tissue repairing, M2), are
      not spontaneously recruited in sufficient numbers to sites of injured central
      nervous system (CNS). We further demonstrated that their exogenous administration
      to the margins of injured spinal cord improved functional outcome. However, our
      suggestions evoked criticism, claiming that we were adding macrophages to a site
      that is already overwhelmed with inflammatory cells. Using experimental paradigms
      that enabled functional distinction between the resident and infiltrating cells,
      our most recent studies further corroborated our repair perception, showing that
      (a) infiltrating monocyte-derived macrophages are recruited following injury and
      localize to the margins of the lesion, unlike the activated resident microglia
      that are not compartmentalized, and (b) activated resident microglia and
      infiltrating monocyte-derived macrophages perform distinct roles; recruited blood
      derived macrophages display an (IL-10-dependent) anti-inflammatory phenotype when
      they become co-localized with the glial scar. We further found that post-injury
      recruitment of blood monocytes is indeed suboptimal. Augmentation of the levels
      of naive blood monocytes leads to their increased recruitment to the same zones
      that are the targets of the infiltrated endogenous monocytes, and they acquire
      the same anti-inflammatory activity, leading to improved recovery. Thus, boosting
      the levels of the relevant blood monocytes reinforces the body's own repair
      mechanisms that, for reasons that are currently under investigation, are not
      optimally triggered within the critical post-injury period.

PMID- 20149865
TI  - Aging and oxidatively damaged nuclear DNA in animal organs.
AB  - Oxidative stress is considered to contribute to aging and is associated with the
      generation of oxidatively damaged DNA, including 8-oxo-7,8-dihydroguanine. We
      have identified 69 studies that have measured the level of oxidatively damaged
      DNA in organs of animals at various ages. In general, organs with limited cell
      proliferation, i.e., liver, kidney, brain, heart, pancreas, and muscle, tended to
      show accumulation of DNA damage with age, whereas organs with highly
      proliferating cells, such as intestine, spleen, and testis, showed more equivocal
      or no effect of age. A restricted analysis of studies reporting a baseline level
      of damaged DNA that was fewer than 5 lesions/10(6) dG showed that 21 of 29
      studies reported age-associated accumulation of DNA damage. The standardized mean
      difference in oxidatively damaged DNA between the oldest and the youngest age
      groups was 1.49 (95% CI 1.03-1.95). There was no difference between age span,
      number of tested organs, statistical power, sex, strain, or breeding between the
      studies showing positive and null effects. Citation and publication bias seems to
      be a problem in the overall dataset, whereas it is less pronounced in the
      restricted dataset. There is compelling evidence for aging-associated
      accumulation of oxidatively damaged DNA in organs with limited cell
      proliferation.

PMID- 20149866
TI  - SMAD3 and EGR1 physically and functionally interact in promoter-specific fashion.
AB  - Gonadotropin-releasing hormone (GNRH1) stimulates luteinizing hormone beta
      subunit (LHB/Lhb) transcription. The transforming growth factor beta superfamily
      ligand activin A partially inhibits this effect on the human LHB promoter while
      potentiating GNRH1-induction of the murine Lhb gene. Here, we investigated the
      mechanisms underlying the species-specific modulation of the GNRH1 response by
      activin signalling. GNRH1 stimulates LHB/Lhb transcription via induction of early
      growth response 1 (EGR1), which binds to the proximal promoter of both species.
      Activin A decreased GNRH1-induced recruitment of EGR1 to the human, but not
      murine, promoter. We hypothesized that the activin A signalling protein, SMAD3,
      might play a role in this system. Indeed, we observed both physical and
      functional interactions between SMAD3 and EGR1. The two proteins interacted via
      the SMAD3 MH2 domain and the EGR1 DNA-binding domain. Analogous to the species
      specific activin A effect on the GNRH1 response, SMAD3 over-expression partially
      inhibited EGR1-induction of the human promoter, while potentiating EGR1-induced
      murine Lhb promoter activity. The proximal murine Lhb promoter contains three
      minimal SMAD-binding elements (SBEs) that are absent from human LHB. Introduction
      of the SBEs into the human promoter converted SMAD3 from an inhibitor to a
      stimulator of EGR1-induced transcription. The converse was observed when the SBEs
      in the murine promoter were replaced by the corresponding human sequences.
      Together, our results suggest a model in which activin A inhibits GNRH1-induction
      of human LHB transcription via an interaction between SMAD3 and EGR1 that
      inhibits the latter's recruitment to the proximal promoter. In contrast, in
      mouse, the presence of SBEs in the promoter allows SMAD3 and EGR1 to function
      synergistically to regulate Lhb transcription. The basis for their functional
      cooperativity is not completely clear, but may involve enhancement of EGR1's
      physical interaction with other important co-factors, including paired-like
      homeodomain transcription factor 1 (PITX1).

PMID- 20149867
TI  - Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption
      in an in vitro model of intestinal epithelial cells.
AB  - Maintenance of the mucosal barrier is a critical function of intestinal
      epithelial tight junction. Berberine is one of the main constituents of Coptidis
      rhizoma, which has been used for patients with gastrointestinal disorders for a
      long time. This study aimed to determine whether berberine could alleviate pro
      inflammatory cytokine-induced intestinal epithelial tight junction damage. Caco-2
      monolayers were treated with tumor necrosis factor-alpha and interferon-gamma to
      induce barrier dysfunction. The protective effect of berberine on tight junctions
      was analyzed by measuring the trans-epithelial electrical resistance (TEER).
      Transmission electron microscopy was used to observe the morphology of tight
      junction, and subcellular localization of tight junction proteins was
      investigated by immunofluorescence microscopy and Western blot. Berberine
      significantly prevented pro-inflammatory cytokines induced decrease in TEER. The
      distortion of tight junction morphology and redistribution of tight junction
      protein occludin was also prevented by berberine treatment. Western blot analysis
      demonstrated that berberine inhibit the dislocation of occludin from raft
      fractions to non-raft fractions in membrane microdomains of tight junctions. We
      concluded that berberine can ameliorate pro-inflammatory cytokines induced
      intestinal epithelia tight junction damage in vitro, and berberine may be one of
      the targeted therapeutic agents that can restore barrier function in intestinal
      disease states.

PMID- 20149868
TI  - Preparation and evaluation of spray-dried hyaluronic acid microspheres for
      intranasal delivery of fexofenadine hydrochloride.
AB  - Hyaluronic acid (HA)-based microspheres containing PEG 6000 and/or sodium
      taurocholate (NaTC) were prepared by the spray-drying method for nasal delivery
      of fexofenadine hydrochloride (HCl). Their physicochemical properties including
      particle size and drug contents were determined, while their morphology examined
      by a scanning electron microscope (SEM). The effects of the solubilizer (PEG
      6000) and the permeation enhancer (NaTC) on the in vitro release characteristics
      of fexofenadine x HCl were observed. Moreover, the in vitro permeation of
      fexofenadine x HCl was determined using the human nasal cell (HNE) monolayers
      cultured on Transwell inserts. After nasal administration, fexofenadine x HCl in
      rabbit plasma was determined by the LC-MS/MS system. Fexofenadine x HCl-loaded
      microspheres were of spherical shape with 20-30 microm mean diameter. The loading
      efficiency was about 95%. In vitro release of fexofenadine x HCl from the
      microspheres was significantly increased with the addition of PEG 6000. Although
      NaTC did not alter the in vitro release of drug from the microspheres, its
      addition further increased the in vitro permeation of fexofenadine x HCl across
      the HNE cell monolayers. Moreover, the bioavailability of fexofenadine x HCl
      after nasal administration of the microsphere formulation to rabbits was
      increased up to about 48% while that of the control solution was only about 3%.
      These results indicated that the HA microsphere formulation could further be
      developed into a clinically useful nasal delivery system of fexofenadine x HCl.

PMID- 20149869
TI  - Tumor targeting of functionalized lipid nanoparticles: assessment by in vivo
      fluorescence imaging.
AB  - Lipid nanoparticles (LNP) coated by a poly(oxyethylene) polymer have been
      manufactured from low cost and human use-approved materials, by an easy, robust,
      and up-scalable process. The incorporation in the formulation of maleimide
      grafted surfactants allows the functionalization of the lipid cargos by targeting
      ligands such as the cRGD peptide binding to alpha(v)beta(3) integrin, a well
      known angiogenesis biomarker. LNP are able to encapsulate efficiently lipophilic
      molecules such as a fluorescent dye, allowing their in vivo tracking using
      fluorescence imaging. In vitro study on HEK293(beta3) cells over-expressing the
      alpha(v)beta(3) integrins demonstrates the functionalization, specific targeting,
      and internalization of cRGD-functionalized LNP in comparison with LNP-cRAD or LNP
      OH used as negative controls. Following their intravenous injection in Nude mice,
      LNP-cRGD can accumulate actively in slow-growing HEK293(beta3) cancer xenografts,
      leading to tumor over skin fluorescence ratio of 1.53+/-0.07 (n=3) 24h after
      injection. In another fast-growing tumor model (TS/A-pc), tumor over skin
      fluorescence ratio is improved (2.60+/-0.48, n=3), but specificity between the
      different LNP functionalizations is no more observed. The different results
      obtained for the two tumor models are discussed in terms of active cRGD targeting
      and/or passive nanoparticle accumulation due to the Enhanced Permeability and
      Retention effect.

PMID- 20149870
TI  - Identification, mRNA expression and functional analysis of several yellow family
      genes in Tribolium castaneum.
AB  - Querying the genome of the red flour beetle, Tribolium castaneum, with the
      Drosophila melanogaster Yellow-y (DmY-y) protein sequence identified 14 Yellow
      homologs. One of these is an ortholog of DmY-y, which is required for cuticle
      pigmentation (melanization), and another is an ortholog of DmY-f/f2, which
      functions as a dopachrome conversion enzyme (DCE). Phylogenetic analysis
      identified putative T. castaneum orthologs for eight of the D. melanogaster
      yellow genes, including DmY-b, -c, -e, -f, -g, -g2, -h and -y. However, one clade
      of five beetle genes, TcY-1-5, has no orthologs in D. melanogaster. Expression
      profiles of all T. castaneum yellow genes were determined by RT-PCR of pharate
      pupal to young adult stages. TcY-b and TcY-c were expressed throughout all
      developmental stages analyzed, whereas each of the remaining yellow genes had a
      unique expression pattern, suggestive of distinct physiological functions. TcY-b,
      -c and -e were all identified by mass spectrometry of elytral proteins from young
      adults. Eight of the 14 genes showed differential expression between elytra and
      hindwings during the last three days of the pupal stage when the adult cuticle is
      synthesized. Double-stranded RNA (dsRNA)-mediated transcript knockdown revealed
      that TcY-y is required for melanin production in the hindwings, particularly in
      the region of the pterostigma, while TcY-f appears to be required for adult
      cuticle sclerotization but not pigmentation.

PMID- 20149871
TI  - Identification of the chitin-binding proteins from the larval proteins of
      silkworm, Bombyx mori.
AB  - The silkworm is a model organism for Lepidoptera. Its cuticle is composed mainly
      of chitin and proteins, which plays essential roles in multiple physiological
      functions. The binding of proteins to chitin plays an important role for cuticle
      formation. In this research, a chitin-binding assay followed by a proteomics
      analysis was carried out using the proteins extracted from the 5th instar larval
      cuticles. As results, twenty-two proteins were identified including nine
      cuticular proteins, two lysozyme precursors, two proteins with chitin-binding
      type 2 domains, and other proteins. A cuticular protein with the RR-1 consensus,
      BmorCPR56, and a silkworm Tweedle protein, BmorCPT1, were detected in the chitin
      binding fraction for the first time and their chitin-binding activities were
      further confirmed in vitro. The results of this research increase our
      understanding of the structure of the silkworm larval cuticle.

PMID- 20149872
TI  - Triflusal reduces dense-core plaque load, associated axonal alterations and
      inflammatory changes, and rescues cognition in a transgenic mouse model of
      Alzheimer's disease.
AB  - Inflammation has been associated with the two classic lesions in the Alzheimer's
      (AD) brain, amyloid deposits and neurofibrillary tangles. Recent data suggest
      that Triflusal, a compound with potent anti-inflammatory effects in the central
      nervous system in vivo, might delay the conversion from amnestic mild cognitive
      impairment to a fully established clinical picture of dementia. In the present
      study, we investigated the effect of Triflusal on brain Abeta accumulation,
      neuroinflammation, axonal curvature and cognition in an AD transgenic mouse model
      (Tg2576). Triflusal treatment did not alter the total brain Abeta accumulation
      but significantly reduced dense-cored plaque load and associated glial cell
      proliferation, proinflammatory cytokine levels and abnormal axonal curvature, and
      rescued cognitive deficits in Tg2576 mice. Behavioral benefit was found to
      involve increased expression of c-fos and BDNF, two of the genes regulated by
      CREB, as part of the signal transduction cascade underlying the molecular basis
      of long-term potentiation. These results add preclinical evidence of a
      potentially beneficial effect of Triflusal in AD.

PMID- 20149873
TI  - Enhanced cognitive performance of dopamine D3 receptor "knock-out" mice in the
      step-through passive-avoidance test: assessing the role of the
      endocannabinoid/endovanilloid systems.
AB  - Increasing evidence suggests a pivotal role of the D3 receptor (D3R) in cognitive
      processes and the involvement of endocannabinoid/endovanilloid signaling in the
      pathophysiology of neurodegenerative disorders such as Alzheimer's disease. This
      study was undertaken to investigate both the basal and beta-amyloid peptide 1-42
      (BAP 1-42)-impaired cognitive performance of D3R((-/-)) mice, and the role
      therein of endocannabinoids/endovanilloids. D3R((-/-)) mice were either untreated
      or injected i.c.v. with 400 pMol BAP 1-42 or vehicle to be tested 14 days later
      in a step-through passive-avoidance paradigm. The CB(1) receptor antagonist,
      rimonabant (1mg/kg), or the transient receptor potential vanilloid-type 1 channel
      (TRPV1) antagonist SB366791, were injected intraperitoneally for 11 or 7 days.
      The retention test was performed 1, 7 and 14 days after the learning trial. Wild
      type (WT) mice were subjected to the same procedures. D3R((-/-)) mice exhibited a
      better basal cognitive performance as compared to WT mice (p<0.001), which was
      reversed by TRPV1 antagonism. BAP 1-42 induced a pronounced worsening of the
      passive-avoidance response in all tests and in both genotypes (p<0.001).
      Rimonabant treatment never affected the cognitive performance of healthy mice,
      but fully counteracted BAP 1-42-induced amnesic effects in both D3R((-/-)) and WT
      mice only when administered for 11 days, whereas, when administered for 7 days,
      only transiently affected WT mice and caused more prolonged cognitive
      ameliorations in D3R((-/-)) mice. These results support the involvement of D3R
      and TRPV1 in cognitive processes and the concept that A beta peptides inhibit
      memory retention in mice through the involvement of endocannabinoids.

PMID- 20149874
TI  - Magnetic nanoparticles and targeted drug delivering.
AB  - Magnetic nanoparticles (MNPs) are being of great interest due to their unique
      purposes. Especially in medicine, application of MNPs is much promising. MNPs
      have been actively investigated as the next generation of targeted drug delivery
      for more than thirty years. The importance of targeted drug delivery and targeted
      drug therapy is to transport a drug directly to the centre of the disease under
      various conditions and thereby treat it deliberately, with no effects on the
      body. Usage of MNPs depends largely on the preparation processes to select
      optimal conditions and election agents to modify their surface. This review
      summarizes the most commonly used functionalization methods of the MNPs
      preparation methods and their use in targeted drug delivery and targeted therapy.

PMID- 20149876
TI  - A new method for describing the helical conformation of collagen: dependence of
      the triple helical twist on amino acid sequence.
AB  - Collagen fibre diffraction patterns are typically interpreted assuming a
      monotonous, average triple helical conformation for the collagen molecule. Two
      different helical symmetries have been proposed: seven residues in two turns
      versus 10 residues in three turns. Collagen model peptides show predominantly the
      7-fold symmetry but provide evidence for local changes in the helical twist,
      which are related to some extent to the local sequence of the peptides but also
      to the lattice interactions in the crystal. Thus, it is difficult to determine
      precisely to what degree the amino acid sequence dictates the fine details of
      collagen conformation. A new method is presented here in which an internal triple
      helical twist is defined. This method takes into consideration all three chains
      simultaneously, and facilitates investigating the sequence dependence of helical
      twist variation, the conformational consequences of collagen interruptions, and
      the effects on collagen conformation introduced upon receptor or ligand-binding.
      Analysis of the crystal structures of model peptides suggests that collagen
      varies gradually and continuously its helical twist according to the local
      distribution of imino acid residues, with the 7-fold and 10-fold symmetries
      representing the limits of this variation for the cases of imino acid saturation
      or absence, respectively.

PMID- 20149875
TI  - The effects of PKCalpha phosphorylation on the extensibility of titin's PEVK
      element.
AB  - Post-translational modifications, along with isoform splicing, of titin determine
      the passive tension development of stretched sarcomeres. It was recently shown
      that PKCalpha phosphorylates two highly-conserved residues (S26 and S170) of the
      PEVK region in cardiac titin, resulting in passive tension increase. To determine
      how each phosphorylated residue affects myocardial stiffness, we generated three
      recombinant mutant PEVK fragments (S26A, S170A and S170A/S26A), each flanked by
      Ig domains. Single-molecule force spectroscopy shows that PKCalpha decreases the
      PEVK persistence length (from 0.99 to 0.68 nm); the majority of this decrease is
      attributable to phosphorylation of S26. Before PKCalpha, all three mutant PEVK
      fragments showed at least 40% decrease in persistence length compared to
      wildtype. Furthermore, Ig domain unfolding force measurements indicate that
      PEVK's flanking Ig domains are relatively unstable compared to other titin Ig
      domains. We conclude that phosphorylation of S26 is the primary mechanism through
      which PKCalpha modulates cardiac stiffness.

PMID- 20149878
TI  - A generalized method to estimate waveforms common across trials from EEGs.
AB  - We propose a generalized method to estimate waveforms common across trials from
      electroencephalographic (EEG) data. From single/multi-channel EEGs, the proposed
      method estimates the number of waveforms common across trials, their delays in
      individual trials, and all of the waveforms. After verifying the performance of
      this method by a number of simulation tests with artificial EEGs, we apply it to
      EEGs during a Go/NoGo task. This method can be used in general situations where
      the number and the delays of EEG waveforms common across trials are unknown.

PMID- 20149877
TI  - MuRF1 is a muscle fiber-type II associated factor and together with MuRF2
      regulates type-II fiber trophicity and maintenance.
AB  - MuRF1 is a member of the RBCC (RING, B-box, coiled-coil) superfamily that has
      been proposed to act as an atrogin during muscle wasting. Here, we show that
      MuRF1 is preferentially induced in type-II muscle fibers after denervation.
      Fourteen days after denervation, MuRF1 protein was further elevated but remained
      preferentially expressed in type-II muscle fibers. Consistent with a fiber-type
      dependent function of MuRF1, the tibialis anterior muscle (rich in type-II muscle
      fibers) was considerably more protected in MuRF1-KO mice from muscle wasting when
      compared to soleus muscle with mixed fiber-types. We also determined fiber-type
      distributions in MuRF1/MuRF2 double-deficient KO (dKO) mice, because MuRF2 is a
      close homolog of MuRF1. MuRF1/MuRF2 dKO mice showed a profound loss of type-II
      fibers in soleus muscle. As a potential mechanism we identified the interaction
      of MuRF1/MuRF2 with myozenin-1, a calcineurin/NFAT regulator and a factor
      required for maintenance of type-II muscle fibers. MuRF1/MuRF2 dKO mice had lost
      myozenin-1 expression in tibialis anterior muscle, implicating MuRF1/MuRF2 as
      regulators of the calcineurin/NFAT pathway. In summary, our data suggest that
      expression of MuRF1 is required for remodeling of type-II fibers under
      pathophysiological stress states, whereas MuRF1 and MuRF2 together are required
      for maintenance of type-II fibers, possibly via the regulation of myozenin-1.

PMID- 20149879
TI  - Opportunities and pitfalls in the quantification of fiber integrity: what can we
      gain from Q-ball imaging?
AB  - The quantification of fiber integrity is central to the clinical application of
      diffusion imaging. Compared to diffusion tensor imaging (DTI), Q-ball imaging
      (QBI) allows for the depiction of multiple fiber directions within a voxel.
      However, this advantage has not yet been shown to translate directly to superior
      quantification of fiber integrity. Furthermore, recent developments in QBI
      reconstruction with solid angle consideration have led to sharper and
      intrinsically normalized orientation distribution functions. The implications of
      this technique on quantification are also unknown. To investigate this, the
      generalized fractional anisotropy (GFA) from the original and the more recent QBI
      reconstruction scheme and the DTI derived fractional anisotropy (FA) were
      evaluated comparatively using Monte Carlo simulations and real MRI measurements
      of crossing fiber phantoms. Contrast-to-noise ratio, accuracy, independence of
      the acquisition setup and the relation of single fiber anisotropies to measured
      anisotropy in crossings were assessed. In homogeneous single-fiber regions at b
      values around 1000 s/mm2, the FA performed best. While the original QBI
      reconstruction does not show a clear advantage even at higher b-values and in
      crossing regions, the new reconstruction scheme yields superior properties and is
      recommended for quantification at higher b-values and especially in regions of
      heterogeneous fiber configuration.

PMID- 20149880
TI  - Antipsychotics reverse abnormal EEG complexity in drug-naive schizophrenia: a
      multiscale entropy analysis.
AB  - Multiscale entropy (MSE) analysis is a novel entropy-based approach for measuring
      dynamical complexity in physiological systems over a range of temporal scales. To
      evaluate this analytic approach as an aid to elucidating the pathophysiologic
      mechanisms in schizophrenia, we examined MSE in EEG activity in drug-naive
      schizophrenia subjects pre- and post-treatment with antipsychotics in comparison
      with traditional EEG analysis. We recorded eyes-closed resting-state EEG from
      frontal, temporal, parietal, and occipital regions in drug-naive 22 schizophrenia
      and 24 age-matched healthy control subjects. Fifteen patients were re-evaluated
      within 2-8 weeks after the initiation of antipsychotic treatment. For each
      participant, MSE was calculated on one continuous 60-s epoch for each
      experimental session. Schizophrenia subjects showed significantly higher
      complexity at higher time scales (lower frequencies) than did healthy controls in
      fronto-centro-temporal, but not in parieto-occipital regions. Post-treatment,
      this higher complexity decreased to healthy control subject levels selectively in
      fronto-central regions, while the increased complexity in temporal sites remained
      higher. Comparative power analysis identified spectral slowing in frontal regions
      in pre-treatment schizophrenia subjects, consistent with previous findings,
      whereas no antipsychotic treatment effect was observed. In summary, multiscale
      entropy measures identified abnormal dynamical EEG signal complexity in anterior
      brain areas in schizophrenia that normalized selectively in fronto-central areas
      with antipsychotic treatment. These findings show that entropy-based analytic
      methods may serve as a novel approach for characterizing and understanding
      abnormal cortical dynamics in schizophrenia and elucidating the therapeutic
      mechanisms of antipsychotics.

PMID- 20149881
TI  - Transformations in oscillatory activity and evoked responses in primary
      somatosensory cortex in middle age: a combined computational neural modeling and
      MEG study.
AB  - Oscillatory brain rhythms and evoked responses are widely believed to impact
      cognition, but relatively little is known about how these measures are affected
      by healthy aging. The present study used MEG to examine age-related changes in
      spontaneous oscillations and tactile evoked responses in primary somatosensory
      cortex (SI) in healthy young (YA) and middle-aged (MA) adults. To make specific
      predictions about neurophysiological changes that mediate age-related MEG
      changes, we applied a biophysically realistic model of SI that accurately
      reproduces SI MEG mu rhythms, containing alpha (7-14 Hz) and beta (15-30 Hz)
      components, and evoked responses. Analyses of MEG data revealed a significant
      increase in prestimulus mu power in SI, driven predominately by greater mu-beta
      dominance, and a larger and delayed M70 peak in the SI evoked response in MA.
      Previous analysis with our computational model showed that the SI mu rhythm could
      be reproduced with a stochastic sequence of rhythmic approximately 10 Hz
      feedforward (FF) input to the granular layers of SI (representative of lemniscal
      thalamic input) followed nearly simultaneously by approximately 10 Hz feedback
      (FB) input to the supragranular layers (representative of input from high order
      cortical or non-specific thalamic sources) (Jones et al., 2009). In the present
      study, the model further predicted that the rhythmic FF and FB inputs become
      stronger with age. Further, the FB input is predicted to arrive more
      synchronously to SI on each cycle of the 10 Hz input in MA. The simulated
      neurophysiological changes are sufficient to account for the age-related
      differences in both prestimulus mu rhythms and evoked responses. Thus, the model
      predicts that a single set of neurophysiological changes intimately links these
      age-related changes in neural dynamics.

PMID- 20149883
TI  - The interrelationship of dopamine D2-like receptor availability in striatal and
      extrastriatal brain regions in healthy humans: a principal component analysis of
      [18F]fallypride binding.
AB  - Individual differences in dopamine D2-like receptor availability arise across all
      brain regions expressing D2-like receptors. However, the interrelationships in
      receptor availability across brain regions are poorly understood. To address this
      issue, we examined the relationship between D2-like binding potential (BPND)
      across striatal and extrastriatal regions in a sample of healthy participants.
      PET imaging was performed with the high affinity D2/D3 ligand [18F]fallypride in
      45 participants. BPND images were submitted to voxel-wise principal component
      analysis to determine the pattern of associations across brain regions.
      Individual differences in D2-like BPND were explained by three distinguishable
      components. A single component explained almost all of the variance within the
      striatum, indicating that individual differences in receptor availability vary in
      a homogenous manner across the caudate, putamen, and ventral striatum. Cortical
      BPND was only modestly related to striatal BPND and mostly loaded on a distinct
      component. After controlling for the general level of cortical D2-like BPND, an
      inverse relationship emerged between receptor availability in the striatum and
      the ventral temporal and ventromedial frontal cortices, suggesting possible cross
      regulation of D2-like receptors in these regions. The analysis additionally
      revealed evidence of: (1) a distinct component involving the midbrain and limbic
      areas; (2) a dissociation between BPND in the medial and lateral temporal
      regions; and (3) a dissociation between BPND in the medial/midline and lateral
      thalamus. In summary, individual differences in D2-like receptor availability
      reflect several distinct patterns. This conclusion has significant implications
      for neuropsychiatric models that posit global or regionally specific
      relationships between dopaminergic tone and behavior.

PMID- 20149884
TI  - Localization of the magnetic equivalent of the ERN and induced oscillatory brain
      activity.
AB  - It has been found in numerous electroencephalographic (EEG) studies that a
      negative potential arises following an erroneous response (so-called Error
      Related Negativity, ERN). This typical component of the EEG has, however, proven
      more difficult to identify when transferring analogous paradigms to
      magnetoencephalography (MEG). The aim of this study was to devise and apply a
      paradigm to elicit erroneous responses and using MEG to measure both the error
      related evoked brain activity (mERN) as well as accompanying induced oscillatory
      activity. Results clearly demonstrate that it is possible to measure the mERN and
      to identify cortical sources associated with it. Using distributed source
      modeling, it is possible to identify the mERN in source space and corroborate EEG
      findings, with the mERN generated in the anterior cingulate cortex (ACC). This
      supports notions regarding the role of the ACC in error monitoring and cognitive
      control of motor behavior. Furthermore, changes in induced oscillatory activity
      were observed in the theta and beta bands. This extends previous studies, which
      show that evoked theta activity could underlie the generation of the ERN.

PMID- 20149885
TI  - Oscillatory gamma synchronization binds the primary and secondary somatosensory
      areas in humans.
AB  - Induced gamma activity has a key role in the temporal binding of distributed
      cortico-cortical processing. To elucidate the neural synchronization in the early
      stage somatosensory processing, we studied the functional connectivity between
      the primary and secondary somatosensory cortices (SI and SII) in healthy subjects
      using magnetoencephalography (MEG) with excellent spatiotemporal resolution.
      First, somatosensory-evoked magnetic fields were recorded to determine the
      locations of each cortical activity. Then we analyzed the phase-locking values
      (PLVs) of the induced gamma activity to assess neural synchrony within the
      somatosensory cortical network. We also assessed PLVs in patients with multiple
      sclerosis (MS) to validate our PLV analysis in evaluating the inter-areal
      functional connectivity, which can often be impaired in MS. The PLVs of the
      induced gamma activity were calculated for each pair of unaveraged MEG signals
      that represented the activities of the contralateral SI and bilateral SII areas.
      Analysis of PLVs between the SI and SII areas showed significantly increased PLVs
      for gamma-band activities, starting at an early post-stimulus stage in normal
      controls, whereas this increase in PLVs was apparently diminished in MS. The PLV
      analysis provided evidence for early-latency, gamma-band neuronal synchronization
      between the SI and SII areas in normal controls. Our study first demonstrates the
      gamma-band synchrony in the early-stage human somatosensory processing.

PMID- 20149882
TI  - Nanoplatforms for constructing new approaches to cancer treatment, imaging, and
      drug delivery: what should be the policy?
AB  - Nanotechnology is the design and assembly of submicroscopic devices called
      nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of
      nanotechnology for the diagnosis and treatment of human disease. Disease-specific
      receptors on the surface of cells provide useful targets for nanoparticles.
      Because nanoparticles can be engineered from components that (1) recognize
      disease at the cellular level, (2) are visible on imaging studies, and (3)
      deliver therapeutic compounds, nanotechnology is well suited for the diagnosis
      and treatment of a variety of diseases. Nanotechnology will enable earlier
      detection and treatment of diseases that are best treated in their initial
      stages, such as cancer. Advances in nanotechnology will also spur the discovery
      of new methods for delivery of therapeutic compounds, including genes and
      proteins, to diseased tissue. A myriad of nanostructured drugs with effective
      site-targeting can be developed by combining a diverse selection of targeting,
      diagnostic, and therapeutic components. Incorporating immune target specificity
      with nanostructures introduces a new type of treatment modality, nano
      immunochemotherapy, for patients with cancer. In this review, we will discuss the
      development and potential applications of nanoscale platforms in medical
      diagnosis and treatment. To impact the care of patients with neurological
      diseases, advances in nanotechnology will require accelerated translation to the
      fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in
      nanoplatform, nano-imaging, and nano-drug delivery will drive the future
      development of nanomedicine, personalized medicine, and targeted therapy. We
      believe that the formation of a science, technology, medicine law-healthcare
      policy (STML) hub/center, which encourages collaboration among universities,
      medical centers, US government, industry, patient advocacy groups, charitable
      foundations, and philanthropists, could significantly facilitate such
      advancements and contribute to the translation of nanotechnology across medical
      disciplines.

PMID- 20149887
TI  - Population analyses of the vascular plant pathogen Verticillium dahliae detect
      recombination and transcontinental gene flow.
AB  - The fungal pathogen Verticillium dahliae has resulted in significant losses in
      numerous crops in coastal California, but lettuce remained unaffected until the
      mid-1990s. Since then outbreaks have decimated entire fields, but the causes of
      this sudden susceptibility of lettuce remain elusive. The population structure of
      V. dahliae isolated from coastal California (n=123) was investigated with 22
      microsatellite markers, and compared with strains from tomato in central
      California (n=60), spinach seed imported from Washington State and Northern
      Europe (n=43), and ornamentals from Wisconsin (n=17). No significant
      differentiation was measured among hosts in coastal California or with the
      spinach and Wisconsin ornamental sampling groups. In contrast, the tomato
      sampling group was significantly differentiated. Significant gene flow was
      measured among the various geographic and host sampling groups, with the
      exception of tomato. Evidence of recombination in V. dahliae was identified
      through gametic disequilibrium and an exceedingly high genotypic diversity. The
      high incidence of V. dahliae in spinach seed and high planting density of the
      crop are sources of recurrent gene flow into coastal California, and may be
      associated with the recent outbreaks in lettuce.

PMID- 20149886
TI  - Near-isometric flattening of brain surfaces.
AB  - Flattened representations of brain surfaces are often used to visualize and
      analyze spatial patterns of structural organization and functional activity.
      Here, we present a set of rigorous criteria and accompanying test cases with
      which to evaluate flattening algorithms that attempt to preserve shortest-path
      distances on the original surface. We also introduce a novel flattening algorithm
      that is the first to satisfy all of these criteria and demonstrate its ability to
      produce accurate flat maps of human and macaque visual cortex. Using this
      algorithm, we have recently obtained results showing a remarkable, unexpected
      degree of consistency in the shape and topographic structure of visual cortical
      areas within humans and macaques, as well as between these two species.

PMID- 20149888
TI  - Emerging roles of nitric oxide in neurodegeneration.
AB  - Nitric oxide (NO) is a gaseous signaling molecule which has physiological and
      pathological roles in the cell. Under normal conditions, NO is produced by nitric
      oxide synthase (NOS) and can induce physiological responses such as vasodilation.
      However, over-activation of NOS has been linked to a number of human pathological
      conditions. For instance, most neurodegenerative disorders are marked by the
      presence of nitrated protein aggregates. How nitrosative stress leads to
      neurodegeneration is not clear, but various studies suggest that increased
      nitrosative stress causes protein nitration which then leads to protein
      aggregation. Protein aggregates are highly toxic to neurons and can promote
      neurodegeneration. In addition to inducing protein aggregation, recent studies
      show that nitrosative stress can also compromise a number of neuroprotective
      pathways by modifying activities of certain proteins through S-nitrosylation.
      These findings suggest that increased nitrosative stress can contribute to
      neurodegeneration through multiple pathways.

PMID- 20149889
TI  - 13C metabolic flux analysis for larger scale cultivation using gas chromatography
      combustion-isotope ratio mass spectrometry.
AB  - (13)C-based metabolic flux analysis ((13)CMFA) is limited to smaller scale
      experiments due to very high costs of labeled substrates. We measured (13)C
      enrichment in proteinogenic amino acid hydrolyzates using gas chromatography
      combustion-isotope ratio mass spectrometry (GC-C-IRMS) from a series of parallel
      batch cultivations of Corynebacterium glutamicum utilizing mixtures of natural
      glucose and [1-(13)C] glucose, containing 0%, 0.5%, 1%, 2%, and 10% [1-(13)C]
      glucose. Decreasing the [1-(13)C] glucose content, kinetic isotope effects played
      an increasing role but could be corrected. From the corrected (13)C enrichments
      in vivo fluxes in the central metabolism were determined by numerical
      optimization. The obtained flux distribution was very similar to those obtained
      from parallel labeling experiments using conventional high labeling GC-MS method
      and to published results. The GC-C-IRMS-based method involving low labeling
      degree of expensive tracer substrate, e.g. 1%, is well suited for larger
      laboratory and industrial pilot scale fermentations.

PMID- 20149890
TI  - Relationship between concentrations of progesterone, oxytocin, noradrenaline,
      gene expression and protein level for their receptors in corpus luteum during
      estrous cycle in the cow.
AB  - The aim of these studies was to evaluate of the relationship between luteal
      concentrations of oxytocin (OT), noradrenaline (NA), progesterone (P4), oxytocin
      receptors (OT-R) and beta(2)-adrenoreceptors (beta(2)-R) gene expression and
      their protein level throughout the estrous cycle in cattle. Corpora lutea (CL)
      collected during days 1-5, 6-10, 11-16 and 17-21 of the estrous cycle were used
      in these studies. Concentrations of P4, OT and NA were determined in tissue
      extracts. Gene expression and protein level for OT-R and beta(2)-R were
      investigated by RT-PCR and Western blot, respectively. Luteal concentration of P4
      was higher (P<0.01) on days 6-10 and 11-16 than during days 1-5 and 17-20 of the
      estrous cycle. Concentration of OT was the highest on days 1-5 and 6-10 of the
      estrous cycle. This concentration decreased (P<0.01) during days 11-16 reaching
      the lowest level (P<0.001) on days 17-20 as opposed to days 1-10 of the estrous
      cycle. Expression of OT-R mRNA was lower on days 6-16 (P<0.05) followed by its
      increase on days 17-20 as opposed to the expression observed on days 1-5.
      Expression of OT-R mRNA was negatively correlated (P<0.05) with the profile of OT
      R protein level. This latter parameter was the lowest on days 17-20 and 1-5, and
      the highest on days 6-10 and 11-16. Oxytocin concentration was negatively
      correlated (P<0.05) with expression of OT-R mRNA and positively correlated
      (P<0.001) with OT-R protein level. This protein level was only correlated with P4
      (r=0.59; P<0.05). Concentration of OT was positively correlated with level of P4
      (P<0.001). Concentration of NA was the highest on days 1-5 of the estrous cycle,
      whereas it was similar or lower (P<0.05) on days 6-21. Expression of mRNA for
      beta(2)-R was the lowest on days 1-5 and was highly increased (P<0.05) on days 6
      16. The expression was the highest (P<0.001) on days 17-21 compared to all others
      group of the estrous cycle. Protein level for beta(2)-R was the highest on days 1
      5 and decreased (P<0.05) on days 6-10 and 11-16. The expression was the lowest on
      days 17-20 compared to the beta(2)-R protein level in CL from all others stages
      of the estrous cycle. Protein level for beta(2)-R was positively correlated
      (P<0.05) with the OT concentration. Expression of mRNA for beta(2)-R was
      negatively correlated (P<0.001) with level of beta(2)-R protein. No correlation
      was found between beta(2)-R mRNA expression and NA concentration or between NA
      and P4 concentrations. Results presented in this study suggest an evident
      relationship between OT and NA and may play an important role in the regulation
      of luteal steroidogenesis during all stages of the estrous cycle.

PMID- 20149891
TI  - Directed issue: novel concepts in inflammation.

PMID- 20149892
TI  - Stem cell therapies for ocular surface disease.
AB  - Transparency of the cornea on the front surface of the eye is essential for
      vision. A variety of blinding ocular surface diseases involve the cornea. This
      review focusses on vision loss caused by disruption of the integrity and function
      of the outermost corneal layer (the epithelium) and the stem-cell-based
      therapeutic strategies in use and under development to restore sight in affected
      patients.

PMID- 20149893
TI  - The future of discovery chemistry: quo vadis? Academic to industrial--the
      maturation of medicinal chemistry to chemical biology.
AB  - At Roche, we set out to think about the future role of medicinal chemistry in
      drug discovery in a project involving both Roche internal stakeholders and
      external experts in drug discovery chemistry. To derive a coherent strategy,
      selected scientists were asked to take extreme positions and to derive two
      orthogonal strategic options: chemistry as the traditional mainstream science and
      chemistry as the central entrepreneurial science. We believe today's role of
      medicinal chemistry in industry has remained too narrow. To provide the
      innovation that industry requires, medicinal chemistry must play its part and
      diversify at pace with our increasing understanding of chemical biology and
      network pharmacology.

PMID- 20149894
TI  - Evaluation of different cytotoxic and cytostatic measures for the in vitro
      micronucleus test (MNVit): summary of results in the collaborative trial.
AB  - This paper summarises the data for 14 different chemicals tested for induction of
      micronuclei (MN) in 5 different cell types across 12 different laboratories. All
      14 chemicals induced biologically and statistically significant increases in MN
      frequency in the different cell types (L5178Y, TK6, CHO, CHL, V79) in the absence
      of cytochalasin B at or below target range toxicity (55+5%) irrespective of
      whether relative cell count (RCC), relative increase in cell count (RICC) or
      relative population doubling (RPD) was used as a measure of
      cytotoxicity/cytostasis to select the top concentration. All measures of
      cytotoxicity in the absence of cytochalasin B are therefore considered equally
      acceptable for use, and the responses were comparable to those obtained in the
      presence of cytochalasin B.

PMID- 20149895
TI  - Structure and sensory physiology of the leg scolopidial organs in
      Mantophasmatodea and their role in vibrational communication.
AB  - Individuals of the insect order Mantophasmatodea use species-specific substrate
      vibration signals for mate recognition and location. In insects, substrate
      vibration is detected by mechanoreceptors in the legs, the scolopidial organs. In
      this study we give a first detailed overview of the structure, sensory
      sensitivity, and function of the leg scolopidial organs in two species of
      Mantophasmatodea and discuss their significance for vibrational communication.
      The structure and number of the organs are documented using light microscopy,
      SEM, and x-ray microtomography. Five scolopidial organs were found in each leg of
      male and female Mantophasmatodea: a femoral chordotonal organ, subgenual organ,
      tibial distal organ, tibio-tarsal scolopidial organ, and tarso-pretarsal
      scolopidial organ. The femoral chordotonal organ, consisting of two separate
      scoloparia, corresponds anatomically to the organ of a stonefly (Nemoura
      variegata) while the subgenual organ complex resembles the very sensitive organs
      of the cockroach Periplatena americana (Blattodea). Extracellular recordings from
      the leg nerve revealed that the leg scolopidial organs of Mantophasmatodea are
      very sensitive vibration receptors, especially for low-frequency vibrations. The
      dominant frequencies of the vibratory communication signals of Mantophasmatodea,
      acquired from an individual drumming on eight different substrates, fall in the
      frequency range where the scolopidial organs are most sensitive.

PMID- 20149896
TI  - Dynamics of haplotype frequency change in a CD8+TL epitope of simian
      immunodeficiency virus.
AB  - Deep pyrosequencing of a CD8+TL epitope from the Tat protein of simian
      immunodeficiency virus (SIV) from four infected rhesus macaques carrying the
      restricting MHC allele (Mamu-A*01) for that epitope, revealed that natural
      selection favoring escape mutations led to an increase in the frequency of
      haplotypes in the epitope region that differed from the inoculum. After 20 weeks
      of infection, a new sequence haplotype in the epitope region had increased to a
      frequency greater than 50% in each of the four monkeys (range 57.9-98.9%); but
      the predominant haplotype was not the same in all four monkeys. Thus, even under
      strong selection favoring escape from CD8+TL recognition, the random nature of
      mutation itself is the primary factor affecting which escape mutation is likely
      to become predominant within an individual host. The relationship between the
      frequency of the inoculum haplotype in the epitope region and time post-infection
      approximated a simple hyperbola. On this assumption, the expected ratio of the
      frequencies at the inoculum at two times t(1) and t(2), f(i)(t(2))/f(i)(t(1)),
      will be given by t(1)/t(2). Because standard phylogenetic methods for
      reconstructing ancestral sequences failed to predict the inoculum sequence
      correctly, we used this relationship to predict the inoculum sequence with 100%
      accuracy, given data on haplotype frequencies at different time periods.

PMID- 20149898
TI  - Phosphodiesterase inhibitors in the management of autoimmune disease.
AB  - Phophodiesterases inhibitors (PDEis) act by inhibiting the catabolism of cyclic
      nucleotides, cAMP and cGMP, which are ubiquitously expressed in cells of the
      immune system. Increased levels of cAMP and/or cGMP have been reported to
      decrease the activity of pro-inflammatory TH1 cells, attenuate experimental
      autoimmune encephalomyelitis and experimental arthritis. PDE5i like Sildenafil
      improves endothelial dysfunction and vascular remodelling in patients with
      pulmonary artery hypertension and refractory secondary Raynaud's phenomenon, with
      a potential to cause disease modification in the former. Studies in animal models
      of fibrosis suggest that these drugs have anti-fibrotic effect and may be
      potentially useful in conditions like scleroderma. They also have been shown to
      have renoprotective effect in animal models. The emerging trends make it
      necessary to exploit the full therapeutic potential of this class of drugs in
      various autoimmune diseases like rheumatoid arthritis, scleroderma, profibrotic
      conditions and PAH.

PMID- 20149897
TI  - Re-establishing tolerance to DNA in humanized and murine models of SLE.
AB  - DNA-specific B cells in SLE represent a logical target for therapeutic
      intervention. We hypothesize that it is possible to re-establish tolerance to
      native DNA in SCID mice with cells transferred from SLE patients or from lupus
      prone MRL/lpr mice by administering chimeric molecules, containing a monoclonal
      antibody against inhibitory B cell receptors coupled to a peptide that
      antigenically mimics DNA. These protein-engineered molecules are able to co
      crosslink selectively the antigen receptors of B cells possessing anti-native DNA
      specificity with the inhibitory surface receptors, thus delivering a strong
      suppressive signal.

PMID- 20149899
TI  - Current remedies for vitiligo.
AB  - Vitiligo is a disorder with complex causes and is a type of autoimmune disease in
      which the immune system targets the body's own pigment cells and tissues. Our aim
      is to present an overall view of the current remedies widely adopted for the
      treatment of vitiligo. Medical treatments target the immune system, and try to
      reverse the destruction. The goal is to restore the skin's color by restoring
      healthy melanocytes to the affected area. Apart from melanocytes, vitiligo
      autoantigens appear also on other cells. Even though antibodies to pigment cells
      are not an agent of vitiligo, the most valuable contribution is that anti
      melanocyte antibody reactivity can help in identifying relevant antigens. T cells
      from vitiligo skin are highly reactive towards melanoma cells and serve as an
      effective source to treat melanoma and stays as a solution for vitiligo. There
      have been many treatments to cure vitiligo such as use of steroid creams, PUVA
      (psoralen and ultraviolet A light), narrow band UVB (ultraviolet B), various
      surgical techniques, vitamin D analogues and pseudocatalase. These treatments are
      subjected for undesired side effects whereas some herbal and natural treatments
      act against the immune system with no side effects.

PMID- 20149900
TI  - Aortic involvement in giant cell arteritis.
AB  - Giant cell arteritis (GCA) is a primary large-vessel vasculitis predominantly
      seen in the elderly that preferentially involves the external carotid artery and
      its branches. However, inflammation of the aorta and its branches occurs in a
      subset of patients although symptoms of aortic involvement may appear years after
      the initial diagnosis of GCA. Therefore, aortic involvement has probably been
      underestimated and its incidence may be more frequent than suspected. Systematic
      evaluation of patients with imaging techniques such as magnetic resonance imaging
      angiography (MRA) and positron emission tomography (PET) may reveal that the
      clinical impact of extracranial involvement by GCA may be more relevant than
      previously thought. Regarding the histopathology, there are some similarities
      between chronic periaortitis (including idiopathic retroperitoneal fibrosis,
      inflammatory abdominal aortic aneurysms and perianeurysmal retroperitoneal
      fibrosis), idiopathic aortitis, and GCA, suggesting that all these illnesses
      probably share common pathological mechanisms. Inflammatory aortitis can arise in
      different clinical settings been idiopathic aortitis more frequent than expected
      in surgical specimens of aortic aneurysm surgeries in the general population. In
      the setting of GCA an early diagnosis of aortic involvement is mandatory in order
      to perform a treatment capable of avoiding the chronic and acute complications
      associated with an elevated mortality [1, 2].

PMID- 20149902
TI  - Synthesis and characterization of hydroxyapatite whiskers by hydrothermal
      homogeneous precipitation using acetamide.
AB  - Long and uniform HA whiskers with high crystallinity, controlled morphology and
      high aspect ratio were successfully synthesized by hydrothermal homogeneous
      precipitation using acetamide. Compared with the additive urea, which is commonly
      used to raise the pH to drive nucleation and growth of HA crystals, acetamide has
      a low hydrolysis rate under the required hydrothermal conditions. This allows
      better and easier control, giving rise to rapid growth of whiskers at a low
      supersaturation. Whisker length and width were in turn determined by solution
      conditions, including the concentration of Ca and PO(4). Whiskers had a mean
      length of 60-116 microm and an aspect ratio of 68-103 for starting solutions
      containing 42-84 mmolL(-1) Ca and 25-50 mmolL(-1) PO(4) with a fixed Ca/P ratio
      of 1.67. Such whiskers are favourable for their improved bone bonding and
      bioactivity, as well as their mechanical properties. Whiskers were slightly Ca
      deficient with Ca/P=1.60-1.65, with the preferred direction of growth along the c
      axis. Variation of acetamide concentration did not affect the constitution, the
      crystallinity or the crystal growth habit.

PMID- 20149901
TI  - CO and NO pulmonary diffusing capacity during pregnancy: Safety and diagnostic
      potential.
AB  - This paper reviews the scientific evidence for the safety of carbon monoxide (CO)
      and nitric oxide (NO) inhalation to measure pulmonary diffusing capacity (DL(CO)
      and DL(NO)) in pregnant women and their fetuses. In eight earlier studies, 650
      pregnant women had DL(CO) measurements performed at various times during
      pregnancy, with a minimum of two to four tests per session. Both pregnant
      subjects that were healthy and those with medical complications were tested. No
      study reported adverse maternal, fetal, or neonatal outcomes from the CO
      inhalation in association with measuring DL(CO). Eleven pregnant women, chiefly
      with pulmonary hypertension, and 1105 pre-term neonates, mostly with respiratory
      failure, were administered various dosages of NO (5-80ppm for 4 weeks
      continuously in pregnant women, and 1-20ppm for 15min to 3 weeks for the
      neonates). NO treatment was found to be an effective therapy for pregnant women
      with pulmonary hypertension. In neonates with respiratory failure and pulmonary
      hypertension, NO therapy improved oxygenation and survival and has been
      associated with only minor, transient adverse effects. In conclusion, maternal
      carboxyhemoglobin ([Hb(CO)]) levels can safely increase to 5% per testing session
      when the dose-exposure limit is 0.3% CO inhalation for <or=3min, and for NO,
      80ppm for <or=3min. The risk of late fetal or neonatal death from increased
      Hb(CO) from diffusion testing is considerably less than the risk of death from
      all causes reported by the Centers for Disease Control, and is therefore
      considered "minimal risk".

PMID- 20149903
TI  - Enhanced antiproliferative activity of carboplatin-loaded chitosan-alginate
      nanoparticles in a retinoblastoma cell line.
AB  - In the present study the potential of carboplatin-loaded chitosan-alginate
      nanoparticles (CANPs) for the treatment of retinoblastoma was investigated. The
      carboplatin-loaded CANPs were approximately 300 nm in size, exhibited a high zeta
      potential of approximately 36 mV and drug encapsulation of approximately 20 wt.%.
      The CANPs were further characterized by Fourier transform infrared spectroscopy,
      differential scanning calorimetry and transmission electron microscopy. In vitro
      release studies revealed fast release of approximately 25% of the drug during the
      first 24h, followed by sustained release. CANPs demonstrated greater and
      sustained antiproliferative activity of the drug in a dose- and time-dependent
      manner (carboplatin IC(50)=0.56 microg ml(-1), carboplatin-loaded CANPs
      IC(50)=0.004 microg ml(-1)), as well as an enhanced apoptotic effect as compared
      with the drug in solution in a retinoblastoma cell line (Y79). The higher
      cytotoxic effect of CANPs may be due to their greater cellular uptake as compared
      with native carboplatin. It was also demonstrated that clathrin-mediated
      endocytosis plays a key role in the internalization of CANPs in the Y79 cell
      line. In conclusion, biodegradable chitosan nanoparticles could be used as an
      effective ocular drug delivery system for sustained intracellular delivery of
      carboplatin for the treatment of retinoblastoma.

PMID- 20149905
TI  - COMP-angiopoietin-1 accelerates bone formation during distraction osteogenesis.
AB  - INTRODUCTION: During distraction osteogenesis, new and highly vascularized bone
      is formed, with angiogenesis preceding osteogenesis. We investigated the
      possibility that COMP-Ang1, an angiogenic factor, may facilitate bone formation.
      METHODS: Rats were divided into three groups. Control rats underwent tibial
      distraction without treatment. In the two remaining groups, BSA (100 microg) or
      COMP-Ang1 (100 microg) were injected transcutaneously into the center of the
      distraction zone. Using radiographic and histologic analyses, we assessed total
      bone volume, vascular density, and bone mineral density. Total RNA was prepared
      from regenerated bone and analyzed for osteogenic marker protein expression using
      real-time RT-PCR analysis. RESULTS: Bone formation in the distraction gap
      progressed more quickly in the COMP-Ang1-treated group than in the BSA-treated
      group. Histological findings and immunostaining of endothelial cells for factor
      VIII revealed that Comp-Ang1 group animals exhibited higher levels of
      vascularity. NanoCT and dual-energy X-ray absorptiometry analyses revealed
      increased new bone formation along capillaries in the COMP-Ang1 group compared
      with the BSA group. Runt-related transcription factor 2 and its target genes,
      including bone sialoprotein, type 1 collagen, osteopontin, and osterix, were
      significantly upregulated in the COMP-Ang1 group. CONCLUSIONS: Our results are
      consistent with previous descriptions of the positive relationship between
      angiogenesis and osteogenesis. In addition, our results suggest the potential use
      of COMP-Ang1 as a therapeutic agent for treatment of distracted limbs by
      enhancing angiogenesis.

PMID- 20149904
TI  - Evidence for pleiotropic factors in genetics of the musculoskeletal system.
AB  - There are both theoretical and empirical underpinnings that provide evidence that
      the musculoskeletal system develops, functions, and ages as a whole. Thus, the
      risk of osteoporotic fracture can be viewed as a function of loading conditions
      and the ability of the bone to withstand the load. Both bone loss (osteoporosis)
      and muscle wasting (sarcopenia) are the two sides of the same coin, an involution
      of the musculoskeletal system. Skeletal loads are dominated by muscle action;
      both bone and muscle share environmental, endocrine and paracrine influences.
      Muscle also has an endocrine function by producing bioactive molecules, which can
      contribute to homeostatic regulation of both bone and muscle. It also becomes
      clear that bone and muscle share genetic determinants; therefore the
      consideration of pleiotropy is an important aspect in the study of the genetics
      of osteoporosis and sarcopenia. The aim of this review is to provide an
      additional evidence for existence of the tight genetic co-regulation of muscles
      and bones, starting early in development and still evident in aging. Recently,
      important papers were published, including those dealing with the cellular
      mechanisms and anatomic substrate of bone mechanosensitivity. Further evidence
      has emerged suggesting that the relationship between skeletal muscle and bone
      parameters extends beyond the general paradigm of bone responses to mechanical
      loading. We provide insights into several pathways and single genes, which
      apparently have a biologically plausible pleiotropic effect on both bones and
      muscles; the list is continuing to grow. Understanding the crosstalk between
      muscles and bones will translate into a conceptual framework aimed at studying
      the pleiotropic genetic relationships in the etiology of complex musculoskeletal
      disease. We believe that further progress in understanding the common genetic
      etiology of osteoporosis and sarcopenia will provide valuable insight into
      important biological underpinnings for both musculoskeletal conditions. This may
      translate into new approaches to reduce the burden of both conditions, which are
      prevalent in the elderly population.

PMID- 20149906
TI  - Implication of the calcium sensing receptor and the Phosphoinositide 3-kinase/Akt
      pathway in the extracellular calcium-mediated migration of RAW 264.7 osteoclast
      precursor cells.
AB  - While the processes involved in the formation, maturation and apoptosis of
      osteoclasts have been investigated extensively in previous studies, little is
      known about the mechanisms responsible for the localization and homing of
      osteoclast precursor cells to the bone environment in order to initiate the bone
      remodeling process. Recent studies have suggested that the extracellular Ca(2+)
      (Ca(2+)(o)) concentration gradient present near the bone environment may be one
      of the participating factors, producing a chemoattractant effect on osteoclast
      precursors. Using the murine osteoclast precursor cells of the monocyte
      macrophage lineage, the RAW 264.7 cell line, we have shown that Ca(2+)(o)
      increases the migration of these cells in a directional manner. The participation
      of the calcium sensing receptor (CaR) in this effect was tested by knocking down
      its expression through RNA interference, which resulted in an abolition of the
      migratory response. By the use of specific pathway inhibitors and western blot
      analysis, the phosphoinositide 3-kinase (PI3K)/Akt and phospholipase Cbeta
      pathways were shown to be implicated in the migratory effect. The implication of
      the Akt pathway in the Ca(2+)(o)-induced chemoattraction of RAW 264.7 cells was
      also confirmed by transducing the cells with the fusion protein TAT-dominant
      negative-Akt, which decreased the migratory effect. In contrast, the MAPK
      pathways (ERK1/2, p38 and JNK) were not involved in the production of the
      migratory effect. We conclude that through the activation of the CaR and
      subsequent signaling via the PI3K/Akt pathway, Ca(2+)(o) produces a
      chemoattractant effect on the osteoclast precursor RAW 264.7 cells. These results
      suggest that the Ca(2+)(o) gradient present near the bone may be one of the
      initiating factors for the homing of osteoclast precursors to bone, thus possibly
      playing a role in the initiation of bone remodeling.

PMID- 20149907
TI  - Effects of cyclic hydraulic pressure on osteocytes.
AB  - Bone is able to adapt its composition and structure in order to suit its
      mechanical environment. Osteocytes, bone cells embedded in the calcified matrix,
      are believed to be the mechanosensors and responsible for orchestrating the bone
      remodeling process. Recent in vitro studies have shown that osteocytes are able
      to sense and respond to substrate strain and fluid shear. However the capacity of
      osteocytes to sense cyclic hydraulic pressure (CHP) associated with physiological
      mechanical loading is not well understood. In this study, we subjected osteocyte
      like MLO-Y4 cells to controlled CHP of 68 kPa at 0.5 Hz, and investigated the
      effects of CHP on intracellular calcium concentration, cytoskeleton organization,
      mRNA expression of genes related to bone remodeling, and osteocyte apoptosis. We
      found that osteocytes were able to sense CHP and respond by increased
      intracellular calcium concentration, altered microtubule organization, a time
      dependent increase in COX-2 mRNA level and RANKL/OPG mRNA ratio, and decreased
      apoptosis. These findings support the hypothesis that loading induced cyclic
      hydraulic pressure in bone serves as a mechanical stimulus to osteocytes and may
      play a role in regulating bone remodeling in vivo.

PMID- 20149909
TI  - Cross-calibration of 45calcium kinetics against dynamic histomorphometry in a rat
      model to determine bone turnover.
AB  - Techniques for assessing bone dynamic are in high demand. Calcium (Ca) kinetic
      studies are currently being used in our clinical studies of bone turnover in
      adolescents and elderly. The technique has rarely been compared to the standard
      method of bone dynamic histomorphometry. We perturbed bone turnover through
      ovariectomy and sub-optimal dietary Ca in a female rat model to cross-calibrate
      Ca kinetics against dynamic histomorphometry. Kinetic studies involved oral and
      intravenous administration of (45)Ca and monitoring the tracer in blood, urine,
      feces, and bone over a 3-day period as part of a metabolic Ca balance study.
      Histomorphometric indices of mineral apposition rate, mineralizing surface, and
      bone formation rate were obtained from proximal metaphysis and mid-diaphysis
      region of tibial bone. Bone mineralization and resorption rates at the whole
      skeletal level as evaluated by kinetic studies were significantly correlated with
      the volume-based bone formation rate (BFR/BV) evaluated by dynamic
      histomorphometry in metaphyseal trabecular bone (r=0.72 and r=0.61, respectively,
      p<0.001) and surface-based bone formation rate (BFR/BS) in tibial cortex (r=0.63,
      p<0.001 and r=0.59, p<0.01, respectively). Significant correlations were also
      demonstrated between bone resorption and mineralization rates at the whole
      skeletal level (r=0.91, p<0.001) using (45)Ca kinetic data. Ca kinetic modeling
      showed an increase (p<0.001) in skeletal resorption and formation rates in
      response to ovariectomy (27.6 vs. 13.8 mg/d for bone resorption and 42.7 vs. 28
      mg/d for bone formation in ovariectomized vs. their Sham-operated control
      animals, respectively). Ca kinetic data also showed that bone formation decreased
      by 30% and whole bone balance by 50%, when dietary Ca level was reduced from 0.4%
      to 0.2% (34.2 vs. 23.8 mg/d and 10.4 vs. 5.1 mg/d, respectively, p<0.001). Our
      data suggest that Ca kinetic studies can be used reliably to rapidly detect
      changes in bone turnover at the whole skeletal level in response to
      interventions.

PMID- 20149908
TI  - Effects of trabecular type and orientation on microdamage susceptibility in
      trabecular bone.
AB  - Trabecular architecture becomes more rod-like and anisotropic in osteoporotic and
      aging trabecular bone. In order to address the effects of trabecular type and
      orientation on trabecular bone damage mechanics, microstructural finite element
      modeling was used to identify the yielded tissue in ten bovine tibial trabecular
      bone samples compressed to 1.2% on-axis apparent strain. The yielded tissue was
      mapped onto individual trabeculae identified by an Individual Trabeculae
      Segmentation (ITS) technique, and the distribution of the predicted yielding
      among trabecular types and orientations was compared to the experimentally
      measured microdamage. Although most of the predicted yielded tissue was found in
      longitudinal plates (73+/-11%), the measured microcrack density was positively
      correlated with the proportion of the yielded tissue in longitudinal rods
      (R(2)=0.52, p=0.02), but not in rods of other directions or plates. The overall
      fraction of rods and the fractions of rods along the longitudinal and transverse
      axes were also correlated with the measured microcrack density. In contrast,
      diffuse damage area did not correlate with any of these quantities. These results
      agree with the findings that both in vitro and in vivo microcrack densities are
      correlated with Structure Model Index (SMI), and are also consistent with
      decreased energy to failure in more rod-like trabecular bone. Together the
      results suggest that bending or buckling deformations of rod-like trabeculae may
      make trabecular structures more susceptible to microdamage formation. Moreover,
      while simple strain-based tissue yield criteria may account for macroscopic
      yielding, they may not be suitable for identifying damage.

PMID- 20149911
TI  - The effects of spatial proximity and collinearity on contour integration in
      adults and children.
AB  - We tested adults and children aged 7 and 14 on the ability to integrate contour
      elements across variations in the collinearity of the target elements, their
      spatial proximity, and the relative spacing of the target elements to the
      background noise elements (Delta). When collinearity was high, the strength of
      integration for adults was largely independent of spatial proximity and varied
      only with Delta. It was only when collinearity was less reliable because the
      orientation of the elements was randomly jittered that spatial proximity began to
      influence adults' integration. These patterns correspond well to the probability
      that real-world contours compose a single object: collinear elements are more
      likely to reflect parts of a real object and adults integrate them easily
      regardless of the proximity among those collinear elements. The results from
      children demonstrate a gradual improvement of contour integration throughout
      childhood and the slow development of sensitivity to the statistics of natural
      scenes. Unlike adults, integration in children was limited by spatial proximity
      regardless of collinearity and one strong cue did not compensate for the other.
      Only after age 14 did collinearity, the most reliable cue, come to compensate
      efficiently for spatial proximity.

PMID- 20149912
TI  - A user interface for VR-ready 3D medical imaging by off-the-shelf input devices.
AB  - The distinctiveness of clinical environments demands specific solutions in the
      design of both usable and practical user interfaces for 3D medical imaging. In
      this work, a novel user interface to provide a direct interaction in 3D space by
      off-the-shelf input devices is proposed. The interface, which has been
      implemented and integrated into an open-source medical image viewer, features a
      depth-enhanced mouse pointer and a novel rotation technique that uses the
      object's geometry as the rotation handle. The usability of the proposed approach
      is evaluated to show its effectiveness for use in professional 3D imaging
      applications.

PMID- 20149910
TI  - Long-term dietary restriction influences plasma ghrelin and GOAT mRNA level in
      rats.
AB  - The objective of this study was to examine the effect of chronic dietary
      restriction on the physical characteristics of the intestine and gut-derived
      satiety hormone production. Male Wistar rats (8 weeks) were randomized to ad
      libitum (AL) or 35% dietary restriction (DR) for 5 months. At the end of the
      study, physical measurements were made on the intestine and satiety hormone
      secretion and mRNA expression determined. A comparison group of young, growing AL
      rats (5 weeks) was also examined. The adult DR rats gained less weight over 5
      months and had lower fat mass than adult AL rats (p<0.05). The weight of the
      small intestine as a percentage of total body weight was greater in adult DR
      compared to adult AL but lower than young AL rats. Compared to AL, DR down
      regulated proglucagon and cholecystokinin mRNA in the duodenum and ghrelin mRNA
      in the stomach of adult rats but was not different from young AL. Ghrelin-O
      acyltransferase (GOAT) mRNA in the stomach was up-regulated 21-fold in adult AL
      rats compared to young AL and 14-fold compared to adult DR rats. Total and des
      acyl ghrelin was approximately 50% higher in adult DR and young AL rats compared
      to adult AL. Plasma leptin and insulin were lower in adult DR and young AL rats
      compared to adult AL. Our findings suggest that long-term energy deficits
      continue to drive up ghrelin levels which may have profound implications for
      practical implementation of DR as an anti-aging or anti-obesity strategy in
      humans.

PMID- 20149913
TI  - Impact of forest fires on PAH level and distribution in soils.
AB  - Surface (0-5 cm) and subsurface (-5 to 15 cm) soils from burned forest areas in
      South of France were analyzed to determine contents of 14 priority polycyclic
      aromatic hydrocarbons (PAHs) and their distribution profile. The sampling
      procedure allowed us to study the effect of the frequency of fire as well as the
      influence of the time elapsed since the last fire. The contribution of forest
      fires to the content of PAHs in soils was demonstrated, as well as the decrease
      of their total level with time. The hypothesis is that a natural remediation
      takes place a few years after the last fire event. The lowest molecular weight
      studied PAHs (naphthalene, acenaphtene, fluorene, phenanthrene, anthracene,
      fluoranthene and pyrene) appear to be the major ones produced by forest fire.
      Naphtalene levels are remarkably high in burned soils (more than 70 MUg kg(-1),
      i.e. more than 20 times higher than in the control soils) and still remain
      important years after the last fire event. The time elapsed since the last fire
      appears to be a more influencing factor than the fire frequency. The index
      defined from the PAH levels shows values reflecting the time elapsed since the
      last fire.

PMID- 20149914
TI  - [Usefulness of computed tomography and magnetic resonance imaging in the
      diagnosis of Takayasu's arteritis].

PMID- 20149915
TI  - Cross-border reproductive care: now and into the future.
AB  - OBJECTIVE: To introduce the key discussion points from the first International
      Forum on Cross-Border Reproductive Care (CBRC). SETTING: International
      conference. CONCLUSION(S): A number of similar concerns were raised by the
      international panel of attendees at the International Forum on CBRC. The primary
      concerns of health care providers were the lack of reliable and complete
      information on the numbers of CBRC cases, the types of care being sought, and the
      outcomes of the treatments or pregnancies. To ensure quality of care on both
      international and local scales, physicians and fertility clinic staff of outgoing
      and incoming CBRC patients must be advised on how to best counsel their patients
      on safety and efficacy.

PMID- 20149916
TI  - Cross-border fertility services in North America: a survey of Canadian and
      American providers.
AB  - OBJECTIVE: To identify the scope and volume of cross-border fertility services in
      Canada and the U.S. and to evaluate the three-way communication between patients
      and their service providers in 2008. DESIGN: Mail and on-line surveys of cross
      border fertility care activity were sent to 34 Canadian and 392 American
      fertility clinics and clinicians. MAIN OUTCOME MEASURE(S): Clinician and patient
      experience with assisted reproductive technologies. RESULT(S): The most commonly
      reported cross-border treatment sought by Canadians was anonymous donor-oocyte in
      vitro fertilization (IVF; 363 out of 452, 80%). For patients entering Canada to
      receive fertility treatment, the largest demand was for IVF (106 out of 146,
      73%). The majority of out-of-country patients received by U.S. clinics sought
      standard IVF (927 out of 1,809, 51%), most of these coming from Europe (25%) and
      Latin America (39%). The largest proportion of patients leaving the U.S. to
      receive IVF (41%) or donor-egg IVF (52%) traveled to India/Asia. Concurrence was
      seen between Canadian and U.S. clinics' ratings of key data that should be
      provided along with returning patients. Experience of earlier patients with
      individual centers and perceived safety and effectiveness of care are the key
      factors in choice of destination. CONCLUSION(S): Anonymous donor-oocyte IVF is
      the main assisted reproductive technology sought by Canadians traveling to the
      U.S. India and Asia are the main destinations for U.S. women leaving the country
      for their fertility care. Three-way communication between patients and sending
      and receiving clinics is an important element of safe and effective care.

PMID- 20149917
TI  - Optic neuropathy and a reversible splenial lesion after gastric bypass: shared
      pathophysiology?
AB  - A 22-year-old female presented 2months after a laparascopic gastic bypass with
      3weeks of progressive painless visual loss. Ophthalmologic exam revealed severely
      reduced visual acuity, central scotomas, and optic nerve edema bilaterally. She
      was noted to have a mild encephalopathy. MRI of the brain revealed restricted
      diffusion in the splenium of the corpus callosum. The patient was treated with
      3days of intravenous methylprednisolone, intravenous fluids, and re-institution
      of vitamin supplementation. Four weeks later, she had significant improvement in
      her visual acuity and marked reduction in central scotomas. Her encephalopathy
      resolved and the splenial abnormality disappeared on repeat brain MRI. This is
      the first reported case of a bilateral optic neuropathy and a reversible splenial
      lesion syndrome after gastric bypass. The presentation of both conditions in our
      patient may suggest a shared pathophysiology.

PMID- 20149918
TI  - Copper deficiency associated with severe neurological disorder--a genetic work-up
      of possible mutations in copper transport proteins.
AB  - BACKGROUND: Copper deficiency has been described as resulting in severe
      neurological impairment. However, mechanisms underlying a copper deficiency are
      presently unknown. PATIENTS AND METHODS: We describe three patients suffering
      from severe spasticity, ataxia and hyperreflexia and had laboratory evidence of
      copper deficiency. RESULTS: Genetic analysis of six copper
      transporters/chaperones revealed no mutations, but two SNPs in one copper
      transporter protein and one copper chaperone. CONCLUSIONS: Owing to the severity
      of the disease further research is required to elucidate the mechanisms leading
      to copper deficiency.

PMID- 20149919
TI  - The impact of concomitant infections by Trypanosoma cruzi and intestinal
      helminths on the health of wild golden and golden-headed lion tamarins.
AB  - A 4-year longitudinal epidemiological study was carried out to evaluate the
      effect of infection by Trypanosoma cruzi and three intestinal helminth species on
      the health of golden and golden-headed lion tamarins. We evaluated health using
      analysis of blood counts, serum proteins, electrophoretograms, electrocardiograms
      and a health ranking based on physiological parameters. Among the helminths,
      Trichostrongylidae was demonstrated as the most pathogenic, followed by
      Prosthenorchis sp.; concomitant infection by Spiruridae may exacerbate the
      negative effects of the other two helminths. T. cruzi infection was not highly
      detrimental to the health of the study animals and was correlated with increased
      resilience to helminths. Tamarins younger than 1-year of age or older than 4
      years had lower health condition. Golden-headed lion tamarins were in lower
      health condition because of higher parasitic prevalence. Our data suggest that
      when parasite community pathogenicity and prevalence are high, natural selection
      will allow survival only of lion tamarins in the best health condition.

PMID- 20149920
TI  - [BAC 40 battery: a tool of cognitive evaluation for the diagnosis of Alzheimer's
      disease at the specialist office].
AB  - BAC 40 is a "composite" battery of psychometric tests useful for the diagnosis of
      Alzheimer's dementia. It was elaborated using the modified Mini-Mental Status
      (MMS). The advantage is to establish a diagnosis in less than 20 minutes,
      exploring all the sectors of cognitive life. This tool was validated in a control
      population of 103 aged normal subjects and in 97 patients living at home or in
      institution and attending a neurology outpatient clinic for a memory complain.
      The scores obtained with "BAC 40" and the "ADAS-COG SCALE" were compared in all
      patients. The statistical analysis demonstrated a good correlation between the
      two scales, with a Spearman coefficient of -0.72 for the controls, and -0.90 for
      the patients. Cutoff values were determined below which a pathologic dementia
      process can be highly suspected. Score variations according to different
      parameters, and particularly in function of age, are given.

PMID- 20149921
TI  - More on low-level non-occupational mercury exposure and health concerns.

PMID- 20149922
TI  - Estimation of automobile emissions and control strategies in India.
AB  - Rapid, but unplanned urban development and the consequent urban sprawl coupled
      with economic growth have aggravated auto dependency in India over the last two
      decades. This has resulted in congestion and pollution in cities. The central and
      state governments have taken many ameliorative measures to reduce vehicular
      emissions. However, evolution of scientific methods for emission inventory is
      crucial. Therefore, an attempt has been made to estimate the emissions (running
      and start) from on-road vehicles in Chennai using IVE model in this paper. GPS
      was used to collect driving patterns. The estimated emissions from motor vehicles
      in Chennai in 2005 were 431, 119, 46, 7, 4575, 29, and 0.41 tons/days
      respectively for CO, VOC, NO(x), PM, CO(2,) CH(4) and N(2)O. It is observed from
      the results that air quality in Chennai has degraded. The estimation revealed
      that two and three-wheelers emitted about 64% of the total CO emissions and heavy
      duty vehicles accounted for more than 60% and 36% of the NO(x) and PM emissions
      respectively. About 19% of total emissions were that of start emissions. It is
      also estimated that on-road transport contributes about 6637 tons/day CO(2)
      equivalent in Chennai. This paper has further examined various mitigation options
      to reduce vehicular emissions. The study has concluded that advanced vehicular
      technology and augmentation of public transit would have significant impact on
      reducing vehicular emissions.

PMID- 20149923
TI  - Why do cells release vesicles?
AB  - Prokaryotic and eukaryotic cells release vesicles into their environment. To
      answer the question why eukaryotic cells release vesicles, we may learn from
      prokaryotes. Bacteria release outer membrane vesicles, resembling microparticles,
      which act as "multi-purpose carriers". They contain signalling molecules for
      other bacteria, deliver toxins to host cells and exchange DNA encoding virulence
      genes between bacteria. Similarly, cell-derived microparticles and exosomes from
      eukaryotic cells are multi-purpose carriers containing e.g. signalling molecules,
      cellular waste and functional genetic information. To illustrate our rapidly
      increasing knowledge on the multiple roles that cellular microparticles and
      exosomes play in disease progression, we focus on cancer, which is one of the
      best studied diseases in this aspect. The clinical applications of microparticles
      and exosomes, including diagnosis, prognosis and therapy, in cancer are
      discussed.

PMID- 20149924
TI  - Tissue factor activity under flow.
AB  - Coagulation processes under flow conditions are fundamentally different when
      compared to whole blood clotting in a tube. Due to red blood cell migration
      toward the center of the vessel, platelet concentrations are elevated several
      fold in the plasma layer near the wall or thrombus. Evaluation of platelet
      function, coagulation proteases, and pharmacological agents can utilize closed
      systems of constant volume that lack flow (eg. intracellular calcium measurement,
      automated calibrated thrombography) or include flow (eg. aggregometry or cone-and
      plate viscometry). However, these laboratory approaches fail to recreate the fact
      that intravascular thrombosis is an open system where blood is continually
      flowing over a thrombotic site. In open systems, the rapid accumulation of
      platelets at a surface leads to platelet concentrations greatly exceeding those
      found in whole blood and the delivery/removal of species by convection may impact
      the efficacy of pharmacological agents. During a clotting event under flow,
      platelets can accumulate via adhesion receptors to concentrations that are 10 to
      50-fold higher than that of platelet-rich plasma. Using controlled in vitro
      perfusions of whole blood, it is possible to determine the critical level of
      surface tissue factor needed to trigger full scale coagulation on collagen. Such
      in vitro perfusion systems also allow a determination of the potency of anti
      platelet agents as a function of wall shear rate.

PMID- 20149925
TI  - Elastic system fibers in rat incisor periodontal ligament--immunohistochemical
      study using sections of fresh-frozen un-demineralized tissues.
AB  - The aim of this study was to examine the localization and distribution of the
      components of elastic system fibers in the periodontal ligament of continuously
      erupting rat incisors in an effort to understand the mechanism of the eruption of
      the tooth. Sections of fresh-frozen, un-demineralized incisors of the rat
      mandible were prepared for immunohistochemical localization of elastin, fibrillin
      2 and microfibril-associated glycoprotein-1 (MAGP-1). The structure of the
      periodontal ligament was well preserved in sections of fresh-frozen tissues. At
      the basal region of the ligament, intense immunolabelling for fibrillin-2 and
      MAGP-1 was observed as dot-like structures (transversely sectioned fibers) mainly
      on the tooth side of the ligament close to the cementum. These dot-like
      structures gradually increased in number towards the incisal area and were
      distributed throughout the tooth side of the ligament. This pattern of
      distribution was the same as that of reported oxytalan fibers. Elastin
      immunopositive fibers were also detected in the ligament, although the labelling
      was limited and distribution was sparse. In conclusion, both fibrillin-2 and MAGP
      1 immunopositive fibers may serve as a scaffold for deposition of tropoelastin
      during elastogenesis in the periodontal ligament. They may also provide guidance
      for the migration of fibroblasts to the occlusive side, which generates
      contractile forces for the movement of the tooth for continuous eruption of
      incisors.

PMID- 20149926
TI  - The effect of biphasic electrical stimulation on osteoblast function at anodized
      nanotubular titanium surfaces.
AB  - Over the past decade, nanotechnology (or the use of materials with dimensions
      less than 100 nm in at least one direction) has been proposed to improve the
      lifespan of many biomedical devices, including orthopedic implants. Specifically,
      to improve the cytocompatibility properties of currently used orthopedic
      implants, nanotechnology has been used to create nanometer surface features
      (through anodization) on titanium. In addition to this approach, another
      therapeutic method widely investigated to heal bone fractures is through
      electrical stimulation. Here, the coupling of such nanotechnology approaches and
      electrical stimulation were studied to maximize bone cell functions on titanium.
      Results showed that compared to unstimulated conventional titanium, bone forming
      cell (osteoblast) proliferation and long-term functions (alkaline phosphatase
      synthesis, collagen type I synthesis and calcium deposition) were improved upon
      both the creation of an anodized nanotubular titanium surface and biphasic
      electrical stimulation. Most importantly, when electrical stimulation was
      combined with anodized nanotubular titanium features, osteoblast long-term
      functions were improved the most. Therefore, coupling the positive effects of
      anodized nanotubular titanium topographies with currently used therapeutic
      electrical stimulation should be further studied to improve orthopedic implants.

PMID- 20149927
TI  - Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO
      practice guidelines.
AB  - Since 2002, date of publication of the previous Italian Society of Haematology
      (SIE) practice guidelines for management of myelodysplastic syndromes (MDS),
      novel disease-modifying treatments have been introduced and the SIE commissioned
      an update. After a comprehensive review of the medical literature published since
      January 2001, the Expert Panel formulated recommendations for the management of
      adult and paediatric MDS, graded according to the available evidence. The major
      updates are: first-line hypomethylating agents in patients with INT2-high-risk
      disease; controlled use of first-line lenalidomide in low-INT1 risk transfusion
      dependent patients with 5q deletion; deferasirox in low-INT1 patients with a
      relevant transfusional load; first-line high-dose ESA in low-INT1 patients with
      Hb <10 g/dl and endogenous EPO <500 U/l; allogeneic HSCT first-line therapy for
      INT2- and high-risk patients <65 years without severe co morbidities.

PMID- 20149928
TI  - Continuous and dichotomous outcomes in studies of psychotherapy for adult
      depression: a meta-analytic comparison.
AB  - BACKGROUND: In treatment research on depressive disorders, outcomes can be based
      on continuous outcomes but also on dichotomous outcomes. Although it is possible
      to convert the two types of outcomes to each other, it has not been tested
      whether this results in systematic differences. METHOD: We selected studies on
      psychotherapy for adult depression from an existing database, in which both
      continuous and dichotomous outcomes were presented. We calculated effect sizes
      using both types of outcomes, and compared the results. RESULTS: Although there
      were considerable differences between the two types of outcomes in individual
      studies, both types of outcomes resulted in very similar pooled effect sizes. The
      pooled effect size based on the continuous outcome were somewhat more
      conservative (d=0.59; OR=2.92) than the one based on the dichotomous outcome
      (d=0.64; OR=3.17). Heterogeneity was higher in the analyses based on the
      continuous outcomes than in those based on the dichotomous outcomes. Sensitivity
      analyses and subgroup analyses confirmed that the pooled effect sizes were very
      similar, that the effect sizes were somewhat smaller when the continuous outcomes
      are used, and that heterogeneity was higher in the analyses based on the
      continuous outcomes. CONCLUSION: Overall, the two types of outcomes result in
      comparable pooled effect sizes and can both be used in meta-analyses. However,
      the results of the two types of outcomes should not be used interchangeably,
      because there may be systematic differences in heterogeneity and subgroup
      analyses.

PMID- 20149929
TI  - Growth hormone, prolactin and cortisol response to exercise in patients with
      depression.
AB  - BACKGROUND: A blunted growth hormone and prolactin response to pharmacological
      stress test have previously been found in depressed patients, as well as an
      increased cortisol response to psychosocial stress. This study investigated these
      hormones in response to acute exercise using an incremental bicycle test. METHOD:
      A cross-sectional comparison of cortisol, growth hormone, and prolactin in
      depressed (n=137) and healthy (n=44) subjects during rest and in response to an
      incremental bicycle test. Secondly, we tested the depressed patients again after
      a 4-month randomized naturalistic exercise intervention. RESULTS: Resting plasma
      levels of growth hormone (GH), cortisol, or prolactin (PRL) did not differ
      between depressed and healthy subjects (all p-values>.12). In response to an
      incremental bicycle test the GH (p=.02) and cortisol (p=.05) response in
      depressed was different compared to healthy controls. The effect of acute
      exercise stress on PRL (p=.56) did not differ between depressed and healthy
      subjects. Apart from a decrease in GH response in the strength-training group
      (p=.03) the pragmatic exercise intervention did not affect resting hormonal
      levels, or the response to acute exercise. CONCLUSIONS: Patients with mild to
      moderate depression had a different growth hormone and cortisol response to acute
      exercise stress compared to healthy controls. Strength training was able to
      reduce the growth hormone response to acute exercise stress in this patient
      population. Studies with more rigorous inclusion criteria and higher exercise
      frequencies are needed to evaluate and confirm the possible effect of exercise in
      depressed subjects.

PMID- 20149930
TI  - Characterization of anti-channel catfish IgL sigma monoclonal antibodies.
AB  - This study characterizes three monoclonal antibodies (mAbs) developed against the
      constant (C) region of the immunoglobulin light (IgL) sigma chain isotype of the
      channel catfish, Ictalurus punctatus. Microsphere bead assays and Western blot
      analyses utilizing different recombinant (r) proteins show that these anti
      catfish IgL sigma chain mAbs each specifically recognize the denatured form of
      IgL sigma. Importantly, Western blotting of catfish sera using the anti-IgL sigma
      mAbs also identified an IgL chain-sized immunoreactive band(s) of approximately
      27kDa. It is anticipated that these mAbs in combination with the already existing
      anti-catfish Ig heavy (H) and IgL chain mAbs will be useful in future studies
      examining the functional roles of the different catfish IgL isotypes.

PMID- 20149931
TI  - Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both
      effector and regulatory T cells modulation.
AB  - Rapamycin is an oral immunosuppressant drug previously reported to efficiently
      induce naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T ((n)T(reg)) cells
      re-establishing long-term immune self-tolerance in autoimmune diseases. We
      investigated the effect of rapamycin administration to SJL/j mice affected by
      PLP(139-151)-induced relapsing-remitting experimental autoimmune
      encephalomyelitis (RR-EAE). We found that oral or intraperitoneal treatment at
      the peak of disease or at the end of the first clinical attack, dramatically
      ameliorated the clinical course of RR-EAE. Treatment suspension resulted in early
      reappearance of disease. Clinical response was associated with reduced central
      nervous system demyelination and axonal loss. Rapamycin induced suppression of
      IFN-gamma, and IL-17 release from antigen-specific T cells in peripheral lymphoid
      organs. While CD4(+)FoxP3(+) cells were unaffected, we observed disappearance of
      CD4(+)CD45RB(high) effector T (T(eff)) cells and selective expansion of T(reg)
      cells bearing the CD4(+)CD45RB(low)FoxP3(+)CD25(+)CD103(+) extended phenotype.
      Finally, the dual action of rapamycin on both T(eff) and T(reg) cells resulted in
      modulation of their ratio that closely paralleled disease course. Our data show
      that rapamycin inhibits RR-EAE, provide evidence for the immunological
      mechanisms, and indicate this compound as a potential candidate for the treatment
      of multiple sclerosis.

PMID- 20149932
TI  - Cerebrospinal fluid levels of BAFF and APRIL in untreated multiple sclerosis.
AB  - OBJECTIVE AND SUBJECTS: To examine in vivo levels of BAFF (B-cell activating
      factor of the tumor necrosis factor family) and APRIL (a proliferation-inducing
      ligand) in both the cerebrospinal fluid (CSF) and serum of 30 naive MS patients
      and 79 subjects affected by acute or chronic inflammatory or non-inflammatory
      neurological diseases. DESIGN: Case-control study. RESULTS: No difference among
      groups was evidenced in serum BAFF or APRIL levels. By contrast, CSF levels of
      BAFF in MS (mean 144.3 pg/ml+/-141.2), although not significantly different from
      those observed in NIND (164.2 pg/ml+/-92.0), acute peripheral OIND (243.1 pg/ml+/
      139.0) or chronic OIND (240.2 pg/ml+/-122.5), were significantly higher in acute
      central OIND patients (1274.0 pg/ml+/-803.8; p<0.001 vs. all groups). Similarly,
      CSF APRIL levels in MS (1541.0 pg/ml+/-1071.0), NIND (2629.0 pg/ml+/-1669.0),
      acute peripheral OIND (2834.0 pg/ml+/-1118.) or chronic OIND (2764.0 pg/ml+/
      659.7) were not significantly different, while they were significantly higher in
      acute central OIND (6218.0 pg/ml+/-3790.0; p<0.001 vs. MS and NIND; and p<0.05
      vs. acute peripheral OIND). CONCLUSIONS: Our results strongly suggest that
      further investigation is warranted to elucidate the role of BAFF and APRIL in MS
      and that serum levels of BAFF and APRIL do not reflect CSF levels.

PMID- 20149933
TI  - Quantification of vocal tract configuration of older children with Down syndrome:
      a pilot study.
AB  - OBJECTIVE: To quantify the vocal tract (VT) lumen of older children with Down
      syndrome using acoustic reflection (AR) technology. DESIGN: Comparative study.
      SETTING: Vocal tract lab with sound-proof booth. PARTICIPANTS: Ten children (4
      males and 6 females), aged 9-17 years old diagnosed with Down syndrome. Ten
      typically developing children (4 males and 6 females) matched for age, gender,
      and race. INTERVENTION: Each participant's vocal tract measurements were obtained
      by using an Eccovision Acoustic Pharyngometer. MAIN OUTCOME MEASURES: Six vocal
      tract dimensional parameters (oral length, oral volume, pharyngeal length,
      pharyngeal volume, total vocal tract length, and total vocal tract volume) from
      children with Down syndrome and the typically developing children were measured
      and compared. RESULTS: Children with Down syndrome exhibited small oral cavities
      when compared to control group (F(1,18)=6.55, p=0.02). They also demonstrated a
      smaller vocal tract volumes (F(1,18)=2.58, p=0.13), although the results were not
      statistically significant at the 0.05 level. Pharyngeal length, pharyngeal
      volume, and vocal tract length were not significantly different between the two
      groups. CONCLUSION: Children with Down syndrome had smaller oral cavities, and
      smaller vocal tract volumes. No significant differences were found for pharyngeal
      length, pharyngeal volume, and vocal tract length between these two groups.

PMID- 20149934
TI  - Risk and indicators of condemnation of male turkey broilers in western France,
      February-July 2006.
AB  - A field study was conducted to estimate the sanitary condemnation proportion in
      male turkey broiler flocks, to describe the reasons for condemnation and the
      related macroscopic lesions, and to investigate whether primary production
      information would predict the risk of condemnation. Male turkey standard broiler
      flocks (117) were randomly selected in the 13 slaughterhouses located in Western
      France, from February to July 2006. The flocks were monitored from their arrival
      at the slaughterhouse until the results of the post mortem sanitary inspection.
      Information about rearing conditions, health history, catching and loading
      conditions, transportation to the slaughterhouse and slaughtering was also
      collected. Sampling design was considered in the calculations and the
      condemnation proportion was modelled using a negative binomial regression,
      accounting for clustering within slaughterhouse. The within-flock weighted
      average condemnation proportion was 1.8% (95% confidence interval, 1.3-2.3%).
      Emaciation, arthritis-polyarthritis and congestion were the main reported
      official reasons for condemnation, representing 76% of the condemned carcases.
      Three variables were significantly associated with increased risk of
      condemnation: observed locomotor disorders on the farm, high cumulative mortality
      2 weeks before slaughter, and clinical signs observed by the Veterinary Services
      during the ante mortem inspection at the slaughterhouse. The final model
      explained 35% of the total variation in condemnation risk. Half of this explained
      variation could be attributed to locomotor disorders observed during rearing. The
      sensitivity and specificity of the model to predict a high flock condemnation
      risk were 80% and 74%, respectively, when using an optimum threshold of 0.95% to
      define high risk. The results of this study suggested that the variables found to
      be associated with condemnation proportion were markers of increased risk and
      could be used as indicators. These risk indicators can easily be retrieved from
      the pre-existing regulatory document transmitted before flock arrival at the
      slaughterhouse and could be used to screen flocks before slaughter, according to
      their expected risk of condemnation.

PMID- 20149935
TI  - Systematic review of causes and factors associated with morbidity and mortality
      on smallholder dairy farms in eastern and southern Africa.
AB  - This article presents the first systematic review of the causes and factors
      associated with morbidity and mortality, on smallholder dairy farms in Eastern
      and Southern Africa. It was conducted in August 2007. Primary studies on causes
      of morbidity and mortality on smallholder dairy farms in the region were
      identified, examined and descriptive information extracted. Electronic (CAB
      Abstracts, PubMed, ScienceDirect and Web of Science) and non-electronic databases
      were used to identify and retrieve the primary studies. The retrieval process
      included all types of study designs with no restriction on the year of
      publication and language. Mastitis, tick-borne diseases (TBDs), tick infestation
      and diarrhoea were among the most commonly documented causes of morbidity. TBDs,
      diarrhoea and trypanosomiasis were among the most commonly documented causes of
      mortality; however, a substantial number of mortalities with undiagnosed causes
      were also reported. Factors ranked as most negatively associated with mastitis
      were residual calf suckling and increased water availability on the farm while
      use of common udder towel was the factor most positively associated with
      mastitis. Zero-grazing was ranked as the factor most negatively associated with
      TBDs while age was most positively associated. More intervention studies are
      recommended in the region to better identify animal health constraints and their
      associated risk factors.

PMID- 20149936
TI  - Combining analysis tools and mathematical modeling to enhance and harmonize food
      safety and food defense regulatory requirements.
AB  - The past decade has seen rapid developments in risk assessment techniques and
      tools related to food safety and food defense. These advances are beginning to
      have a significant impact on the decision making processes used by risk managers
      in both government and industry. Furthermore, the highly complex issues currently
      facing the management of food safety risks on an international basis are likely
      to require even more sophisticated assessments. One of the key challenges that
      must be met to advance the adoption of risk analysis principles is learning how
      risk managers can best utilize the results of risk assessments as they must take
      the results of complex stochastic models and adapt the findings to the binary
      decision criteria that are the basis for legal decisions. This will require a
      better articulation of key principles of food safety risk management, such as the
      recently adopted Codex Alimentarius "Principles and Guidelines for the Conduct of
      Microbial Risk Management."

PMID- 20149937
TI  - Survival of lactic acid and chlorine dioxide treated Campylobacter jejuni under
      suboptimal conditions of pH, temperature and modified atmosphere.
AB  - As mild decontamination treatments are gaining more and more interest due to
      increased consumer demands for fresh foods, it is of great importance to
      establish the influence of decontamination treatments on the subsequent bacterial
      behaviour under suboptimal storage conditions. For this purpose Campylobacter
      jejuni cells treated with lactic acid (LA, 3% lactic acid, pH 4.0, 2 min) or
      chlorine dioxide (ClO(2), 20 ppm, 2 min) were inoculated in Bolton broth (pH 6.0)
      and incubated under 80% O(2)/20% N(2), 80% CO(2)/20% N(2), air or micro
      aerophilic (10% CO(2)/85% N(2)/5% O(2)) atmosphere, at 4 degrees C during 7 days.
      Treatment with water served as a control. The most suppressive atmosphere for the
      survival of C. jejuni was O(2)-rich atmosphere, followed by air, micro-aerophilic
      and CO(2)-rich atmosphere. The survival of C. jejuni was dependent on the type of
      initial decontamination treatment, with water treated cells showing the greatest
      survival followed by LA and ClO(2) treated cells. Intracellular pH (pH(i)) of
      individual C. jejuni cells was determined using Fluorescence Ratio Imaging
      Microscopy (FRIM). At all tested conditions, different subpopulation of the cells
      could be distinguished based on their pH(i) values. The pH(i) response was
      independent on the surrounding atmosphere since similar distribution of the
      subpopulations was observed for all tested atmospheres. However, the pH(i)
      response was dependent on the initial decontamination treatment. The
      investigation of intracellular parameters gave an insight into pathogen behaviour
      under stressful conditions at intracellular level. The results obtained in this
      study highlighted the importance of combining decontamination technologies with
      subsequent preservation techniques to the control survival and growth of
      foodborne pathogens.

PMID- 20149938
TI  - Virulence properties of methicillin-susceptible Staphylococcus aureus food
      isolates encoding Panton-Valentine Leukocidin gene.
AB  - In this study, three Panton-Valentine Leukocidin gene carrying methicillin
      susceptible Staphylococcus aureus (MSSA) strains (M1-AAG42B, PY30C-b and YF1B-b)
      were isolated from different food samples in Kesan-Edirne, Turkey. These strains
      were characterized on the basis of MLST type, spa type, virulence factor gene
      contents, antibiotic susceptibilities against 21 antibiotics and biofilm
      formation. The genetic relatedness of the strains was determined by PFGE. In
      addition, the complete gene sequences of lukS-PV and lukF-PV were also
      investigated. All strains were found to be susceptible to tested antibiotics and
      they were mecA negative. Three strains showed the same PFGE band pattern, ST152
      clonal type and t355 spa type. In the detection of virulence factor genes, sea,
      seb, sec, sed, see, seg, seh, sei, sej, sek, sel, sem, sen, seo, sep, seq, seu,
      eta, etb, set1, geh and tst genes were not detected. All strains showed the
      positive results for alpha- and beta-haemolysin genes (hla and hlb), protease
      encoding genes (sspA, sspB and aur), lukE and lukD leukocidin genes (lukED). The
      strains were found to be non-biofilm formers. By this study, the virulence
      properties of the strains were described and this is one of the first reports
      regarding PVL-positive MSSA strains from food.

PMID- 20149940
TI  - (Arene)Ru(II) complexes of epidermal growth factor receptor inhibiting
      tyrphostins with enhanced selectivity and cytotoxicity in cancer cells.
AB  - Ru(eta6-arene) complexes of epidermal growth factor receptor (EGFR) inhibiting
      tyrphostins 1a and 1b were prepared, characterized and tested for DNA interaction
      and bioactivity in four human tumor cell lines. The intrinsic cytotoxicity and
      cell line selectivity of o-hydroxyanisol 1a was greatly enhanced in its Ru(eta6-p
      cymene) complex 2a and in its Ru(eta6-toluene) complex 3a. Complex 2a was
      particularly efficacious against multi-drug resistant EGFR(+) MCF-7/Topo breast
      carcinoma cells and also against mTOR-dependent EGFR(-) HL-60 leukemia cells.
      Complex 3a showed enhanced activity only against 518A2 melanoma cells and HL-60
      cells, which are both known to express the mTOR protein. DNA was strongly
      metallated (ca. 1.7-2%) by all new Ru complexes without undergoing topological
      changes. Apparently, by complexation to Ru fragments tyrphostin derivatives can
      address additional biological targets in a manner instrumental to antitumoral
      strategies.

PMID- 20149939
TI  - Host genes associated with HIV/AIDS: advances in gene discovery.
AB  - Twenty-five years after the discovery of HIV as the cause of AIDS there is still
      no effective vaccine and no cure for this disease. HIV susceptibility shows a
      substantial degree of individual heterogeneity, much of which can be conferred by
      host genetic variation. In an effort to discover host factors required for HIV
      replication, identify crucial pathogenic pathways, and reveal the full armament
      of host defenses, there has been a shift from candidate-gene studies to unbiased
      genome-wide genetic and functional studies. However, the number of securely
      identified host factors involved in HIV disease remains small, explaining only
      approximately 15-20% of the observed heterogeneity - most of which is
      attributable to human lymphocyte antigen (HLA) variants. Multidisciplinary
      approaches integrating genetic epidemiology to systems biology will be required
      to fully understand virus-host interactions to effectively combat HIV/AIDS.

PMID- 20149941
TI  - Discovering some novel tetrahydroquinoline derivatives bearing the biologically
      active sulfonamide moiety as a new class of antitumor agents.
AB  - The present article describes the synthesis of some novel 4-(2-amino-3-cyano-4
      (substituted-aryl)-5-oxo-5,6,7,8-tetrahydroquinolin-1(4H)-yl)benzenesulfonamide
      (23-41) starting with 4-(3-oxo-cyclohex-1-enylamino)benzenesulfonamide (3). All
      the newly synthesized compounds were evaluated for their in vitro antitumor
      activity. Compounds 32, 25, 41, 35, 33, and 37 with IC50 values (2.5, 3, 5, 10,
      12, and 12.5 microg/mL) are more potent and efficacious than Doxorubicin (CAS
      23214-92-8) as reference drug with (IC50 value=37.5 microg/mL). Also, compounds
      28, 30, 31, and 34 (with IC50 values=25 microg/mL) are nearly as active as
      Doxorubicin.

PMID- 20149942
TI  - Altitudinal and thermal gradients of hepatic Cyp1A gene expression in natural
      populations of Salmo trutta from high mountain lakes and their correlation with
      organohalogen loads.
AB  - The biomarker of xenobiotic exposure cytochrome p450A1 (Cyp1A) was used to
      analyze the biological response to chemical pollution in Salmo trutta (brown
      trout) from nine high mountain European lakes in Norway, Tatras, Tyrol, and
      central Pyrenees. Hepatic Cyp1A mRNA levels correlated both with the reciprocal
      of absolute annual average air temperatures of the sampled lakes and with muscle
      concentrations of several hydrophobic organohalogen compounds (OC), including
      chlorinated polychlorobiphenyls (PCB), DDE, and DDT. The correlation between
      Cyp1A expression and OC content was observed across the whole temperature range
      (between -0.7 degrees C and +6.2 degrees C), but also in the absence of any
      thermal gradient. We concluded that airborne pollutants accumulate in high
      mountain lake fish at concentrations high enough to increase Cyp1A expression,
      among other possible effects. As geographical distribution of semi-volatile OC is
      strongly influenced by air temperatures, future climate modifications will
      potentially enhance their physiological effects in lake ecosystems.

PMID- 20149943
TI  - Spatial and seasonal variations of the contamination within water body of the
      Grand Canal, China.
AB  - To delineate the character of contaminations in the Grand Canal, China, a three
      year study (2004-2006) was conducted to investigate variations the water quality
      in the canal. Results showed that the variation of water quality within the Grand
      Canal was of there is remarkable spatial and seasonal heterogeneity regarding
      water quality within the Canal. Values of contaminants in dry-season were
      obviously higher than those in wet-season. Sites influenced strongly by industry
      and urbanization showed higher contents of nutrients and lower levels of
      dissolved oxygen in water body; moreover these sites were severely polluted by
      dissolved metals with the contents of cadmium, chromium and copper exceeding the
      Criteria Maximum Concentration (CMC), US EPA. Multivariate statistical analysis
      suggested nutrient and dissolved metals pollution was the dominant environmental
      problems within the Canal. Anthropogenic influences played a dominant role in the
      character of contaminations in the Grand Canal.

PMID- 20149944
TI  - Trace elements in two marine fish cultured in fish cages in Fujian province,
      China.
AB  - Two cultured marine fish, the Japanese seabass (Lateolabrax japonicus) and red
      seabream (Pagrus major) were collected from eight fish cage sites along the coast
      of Fujian province in China. The concentrations of Ag, As, Cd, Co, Cu, Fe, Mn,
      Se, and Zn in their muscle, stomach and liver tissue were quantified. The risk of
      these trace elements to humans through fish consumption was then assessed. The
      highest concentrations of As, Cd, Se and Zn in fish feed from fish cages were
      found in Dongshan Station. Moreover, the As levels in the muscles of both species
      at all sites were generally higher than China's national standard (>1.0
      microg/g). Trace element concentrations in two marine fish followed the order of
      livers > stomachs > muscles. Although the As levels in two marine caged fish
      exceeded the permissible standards, the estimated daily intake of As did not
      exceed the reference dose guideline established by US EPA. For other trace
      elements examined in this study, their concentrations did not exceed the
      permissible concentrations of the international standards.

PMID- 20149945
TI  - Fathers' behaviors and children's psychopathology.
AB  - The psychological literature on how fathers' behaviors may be related to
      children's psychopathology has grown substantially in the last three decades.
      This growth is the result of research asking the following three overarching
      questions: (1) what is the association between family structure, and particularly
      biological fathers' non-residence, and children's psychopathology, (2) what is
      the association between fathers' parenting and children's psychopathology, and
      (3) what is the association between fathers' psychopathology and children's
      psychopathology. The three broad theoretical perspectives relevant to this
      literature are the standard family environment model, the passive genetic model,
      and the child effects model. The evidence from studies comparing the first two
      models seems to suggest that the origin of the association between parental
      divorce and children's emotional and behavioral problems is largely shared
      environmental in origin, as is the association between resident fathers'
      parenting and children's emotional and behavioral problems, according to studies
      comparing the standard family environment model with the child effects model.
      However, research needs to compare appropriately all theoretical perspectives.
      The paper discusses this, and also points to the importance of considering theory
      driven specificity in modeling effects.

PMID- 20149946
TI  - The effects of different instructional methods on students' acquisition and
      retention of cardiopulmonary resuscitation skills.
AB  - BACKGROUND: The need was evident for the evaluation of applicability and
      effectiveness of different types of instructional strategies to teach CPR skills.
      Therefore, the aim of this study was to evaluate the effects of traditional, case
      based, and web-based instructional methods on acquisition and retention of CPR
      skills. METHODS: Ninety university students (52 female, 48 male) who selected the
      first aid course as an elective were assigned randomly to traditional, case
      based, and web-based instruction groups. The students were tested three times
      (pre-test, post-test and retention test) for their measurable and observable CPR
      skills by using a skill reporter manikin and skill observation checklist.
      RESULTS: Based on the CPR chest compression performance measurements by the skill
      reporter manikin, the web-based instruction group performed poorer than the
      traditional and case-based instruction groups in "average compression rate,
      percentage of correct chest compressions, the number of too low hand positions,
      the number of wrong hand positions, the number of incomplete releases, the
      average number of ventilations, the average volume of ventilations, the minute
      volume ventilations, the number of too fast ventilations, the total number of
      ventilations, and the percentage of correct ventilations" (p<.05). Additionally,
      18-week time interval negatively affected students' performance on "the
      percentage of correct chest compressions, and total number of compressions".
      Similar poor performance by web-based instruction group was also detected by the
      skill observation checklist. CONCLUSION: The students in traditional and case
      based instruction groups showed better CPR performance than students in web-based
      instruction group that used video self-instruction as a learning tool.

PMID- 20149949
TI  - Arthroscopically guided osteotomy for management of intra-articular distal radius
      malunions.
AB  - PURPOSE: A malunion with a step-off of 1 mm or more after an intra-articular
      distal radius fracture may cause pain and arthritic changes at midterm follow-up.
      We present our technique for treating intra-articular distal radius malunions by
      carrying out an osteotomy from inside the joint outward under arthroscopic
      guidance using the dry arthroscopy technique, with emphasis on the clinical and
      radiologic outcomes. METHODS: We performed surgery on 11 patients for intra
      articular malunion of the distal radius 1 to 5 months after the injury.
      Preoperative step-offs ranged from 2 to 5 mm (average, 2.5 mm) on plain
      radiographs. Original fracture patterns involved 1 radial styloid fracture, 1
      radiocarpal fracture-dislocation, and 9 comminuted intra-articular fractures. In
      5 cases an anterior-ulnar or radial styloid fragment was repositioned. In the
      rest, more than 1 fragment (up to 3) was osteotomized. In 1 patient the articular
      osteotomy was combined with an ulnar shortening osteotomy. RESULTS: Follow-up
      ranged from 12 to 48 months. Step-offs were reduced in most cases to 0 mm;
      however, localized gaps (<2 mm) and cartilage defects were commonly seen
      intraoperatively because the fragments did not accurately fit. According to the
      Gartland and Werley score, there were 4 excellent and 7 good results (mean score
      of 2.8). The Modified Green and O'Brien system achieved a mean score of 83, with
      3 excellent, 5 good, and 3 fair results. One patient showed radiolunate narrowing
      on follow-up radiographs. CONCLUSIONS: Arthroscopically assisted osteotomy
      permits direct visualization of the osteotomy site with good midterm clinical and
      radiologic outcomes. The technique can be used in irregularly defined fragments.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 20149951
TI  - CT verified cause of death in hepatic hydrothorax without ascites.
AB  - In patients with cirrhosis of the liver, ascites is a common symptom, some of
      these patients will also present hydrothorax. Under rare circumstances patients
      with liver cirrhosis develop hydrothorax without showing any signs of ascites.
      This study presents one such case and shows autopsy findings consistent with
      hepatic hydrothorax without ascites. Furthermore, we present CT imaging which
      shows the possible cause of death in the case of severe hydrothorax.

PMID- 20149952
TI  - Dual-energy MDCT: comparison of pulmonary artery enhancement on dedicated CT
      pulmonary angiography, routine and low contrast volume studies.
AB  - PURPOSE: The aim of this study was (a) to compare arterial enhancement in
      simultaneously acquired high- and low-kilovoltage images; and (b) to determine
      whether low tube-voltage imaging would permit PE evaluation on routine chest CT
      studies or CTPA studies performed with a low volume of contrast media. MATERIALS
      AND METHODS: We compared 20 CTPA studies (CTPA group), 20 routine thoracic CT
      studies (RT group) and 10 CTPA studies performed with reduced volume of contrast
      media (RC group). HU values were measured in all groups at 80 kVp and 140 kVp
      images in multiple pulmonary arterial segments bilaterally. The diagnostic
      quality of the central and peripheral vascular enhancement and the image noise
      were evaluated at both energies using a five-point scale. RESULTS: For all
      patients, the mean CT attenuation values were greater at 80 kVp than 140 kVp
      images (p<0.001). At 80 kVp, CTPA group attenuation values were greater than RT
      group (p=0.03) with a similar trend at 140 kVp (p=0.08). At both 140 kVp and 80
      kVp, CTPA group attenuation values were greater than RC group (p=0.02 and p=0.03,
      respectively). Qualitative analysis showed that at 140 kVp CTPA studies had
      better global image quality scores than RT (p=0.003) and RC (p=0.001) groups.
      However, at 80 kVp, there was no significant difference of global image quality
      between CTPA and the other groups (p=0.4 and p=0.5, respectively). Although
      measurable image noise was greater at 80 kVp than 140 kVp (p<0.001), qualitative
      analysis revealed lower image noise at 80 kVp images. CONCLUSION: DECT at 80 kVp
      increases arterial enhancement in both CTPA and routine studies. For routine
      studies this results in central and peripheral enhancement quality equivalent to
      that of CTPA studies. Low tube-voltage imaging allows marked contrast volume
      reduction for CTPA. In selected cases, satisfactory lower radiation dose CT might
      be achievable using lower kVp imaging alone.

PMID- 20149953
TI  - Helping women make choices about mammography screening: an online randomized
      trial of a decision aid for 40-year-old women.
AB  - OBJECTIVE: To evaluate the effect of a decision aid (DA) on women's knowledge of
      the benefits and harms of screening and on their ability to make an informed
      decision. METHODS: An online randomized controlled trial among 321 women aged 38
      45 years was conducted. Participants were randomized to either immediate or
      delayed access to the online DA which (i) explained the benefits and harms, (ii)
      included a values clarification exercise and a worksheet to support decision
      making. The primary outcome, knowledge of benefits and harms of screening, and
      secondary outcomes, informed choice (composite of knowledge, values and
      intention), anxiety and acceptability of the DA were measured using online
      questionnaires. RESULTS: Women in the intervention group were more knowledgeable
      (mean score out of 10, 7.35 vs 6.27, p<0.001) and were more likely to have made a
      decision (82% vs 61% p<0.001). Of those who made a decision, women in the
      intervention group were less likely to start screening now (52% vs 65% p=0.05).
      There was no significant difference in the proportion of women who made an
      informed choice (71% intervention group vs 64% control group, p=0.24). The DA was
      helpful, balanced and clear, and did not make women anxious. CONCLUSIONS: The DA
      increased knowledge and reduced indecision, without increasing feelings of
      anxiety. PRACTICE IMPLICATIONS: This decision aid is easy to access online and
      could be an inexpensive way of supporting women aged 40 who are considering
      whether to start screening now, or wait until they are 50. The results of this
      study demonstrate the potential of DAs to help inform women about both the
      benefits and risks of screening at this age and to support women and clinicians
      in this decision making process.

PMID- 20149950
TI  - Psychometric properties of the contingency management competence scale.
AB  - Contingency management (CM) is an evidence-based treatment, and clinicians are
      beginning to implement this intervention in practice. However, little research
      exists on methods for assuring appropriate implementation of CM. This study
      describes the development and psychometric properties of the 12-item CM
      Competence Scale (CMCS). Thirty-five therapists from nine community-based clinics
      participated; following a training period, a randomized trial evaluated the
      efficacy of CM in cocaine abusing patients. Analyses of the CMCS are based on
      ratings from 1613 audiotapes of therapist interactions with 78 patients enrolled
      in the training phase and 103 patients in the randomized phase. Inter-rater
      reliability from 11 raters and internal consistency of items on the CMCS was good
      to excellent. Items loaded onto two factors: one contained items specific to
      discussions of the outcomes of urine testing and reinforcement, and the other
      contained general items related to use of praise, communication of confidence,
      empathy, skillfulness, and maintaining session structure, as well as discussions
      of self-reports of drug use when they occurred. During the training phase in CM
      delivery, scores on the CMCS rose significantly between earlier and later
      training sessions, and during the randomized phase, CM sessions were rated more
      highly than non-CM sessions. Scores on the subscale assessing general items were
      significantly correlated with indices of the therapeutic alliance and predictive
      of durations of cocaine abstinence achieved. These data suggest that the CMCS is
      reliable and valid in assessing delivery of CM and that competence in CM delivery
      is associated with improved patient outcomes.

PMID- 20149954
TI  - Road to help-seeking among (dedicated) human service professionals with burnout.
AB  - OBJECTIVE: Describe and interpret the process of help-seeking among human service
      professionals with burnout. METHODS: Semi-structured interviews were conducted
      with 14 participants. Analysis was conducted using principles of grounded theory.
      RESULTS: All participants were dedicated and responsible workers, selflessly
      giving themselves to their work. Work was demanding, and often included some form
      of organisational change. After a period of time the problems of ill health
      appeared, since persons were overstretching their resources. However, the
      symptoms were denied, since the image of the ideal worker has been internalised
      and persons expected maximum performance from themselves. They kept on working
      hard and delayed the help-seeking process. Eventually, help was sought for
      medical symptoms or by talking to the supervisors. If postponed for too long,
      persons experienced a breaking point. CONCLUSION: Human service professionals
      with burnout internalise the ideal image of their professional role. They strive
      to keep this ideal image at the cost of their own needs, taking a long time to
      seek help for the obstacles they encounter. PRACTICE IMPLICATIONS: More awareness
      raising is needed in order to recognise early burnout symptoms. Particularly
      crucial in this process are supervisors and doctors, who have an authority role
      over employees.

PMID- 20149955
TI  - The effect of physical activity on weight loss is mediated by eating self
      regulation.
AB  - OBJECTIVE: This study tested whether different forms of physical activity (PA)
      were associated with eating self-regulation during weight control, and if changes
      in eating behavior mediated the relationship between PA and weight loss, in
      overweight/obese women. METHODS: 239 women (37.6+/-7.0 years; 31.3+/-4.1kg/m(2))
      participated. The intervention group received a 12-month group behavioral
      treatment designed to increase autonomy and self-regulation for weight control.
      Controls received a health education program. Assessments included body weight,
      structured and lifestyle exercise/PA, and eating self-regulation. RESULTS:
      Moderate+vigorous and lifestyle PA were associated with 12-month change in most
      eating variables (p<0.05) and with body weight change (p<0.01). Mediation
      analysis showed that flexible cognitive restraint and emotional eating fully
      mediated the relation between lifestyle PA and weight change (effect ratio:
      0.63). About 34% of the effect of moderate+vigorous PA on weight change was
      explained by these same mediators (partial mediation). CONCLUSION: Exercise and
      PA may positively influence weight control through eating self-regulation.
      Flexible dietary control and reduced emotional overeating are mechanisms by which
      an active lifestyle can contribute to long-term weight management. PRACTICE
      IMPLICATIONS: Regular exercise and PA can contribute to improved eating behaviors
      during weight management. This could represent an important incentive for people
      seeking weight control.

PMID- 20149956
TI  - Poetry therapy.

PMID- 20149957
TI  - Spinal and limb abnormalities in adolescents with intellectual disabilities.
AB  - There are not many studies pertaining to the spinal or limb abnormalities in
      people with intellectual disabilities, without a clear profile of these
      deformities of them, efforts to understand its characters and improve their
      quality of life will be impossible. Therefore, this paper aims to describe the
      prevalence and related factors of spinal and limb abnormalities in adolescents
      with intellectual disabilities. The participants who participated in health
      examinations as they enrolled into special schools at the first year, a total of
      822 aged 15-18 years adolescents with ID were recruited to this study. The
      results showed that there were 14.5% and 8.5% cases had spinal and limb
      abnormalities based on the physician's observation and X-ray test. Factors of BMI
      level and limb abnormalities were significantly predicted the spinal abnormality
      occurrence in those adolescents with ID. Gender, disability level and have a
      spinal abnormality were variables that can statistically correlate to limb
      abnormality condition. The study highlights that in order to ensure people with
      intellectual disabilities receive an appropriate quality of care, it is important
      to have a precise understanding of the ways in which the needs of them who have
      spinal or limb deformities differ from the sole intellectual disability and the
      general population as a whole.

PMID- 20149958
TI  - Postoperative management of extensor pollicis longus repairs within close
      vicinity to or within the extensor retinaculum.
AB  - Therapists are continually modifying tendon protocols as part of the quest to
      create the perfect balance between tendon protection and tendon glide. Although
      much literature exists on the rehabilitation of the long flexor and extensor
      tendons to the digits, little literature exists on the rehabilitation of the
      extensor pollicis longus (EPL) tendon. This author used concepts related to
      tendon glide, tendon tethering, and early active mobilization to create a new
      splint and subsequent protocol for patients after an EPL laceration near the
      extensor retinaculum.

PMID- 20149959
TI  - Psychological perspective on hand injury and pain.
AB  - NARRATIVE REVIEW: Pain is considered a fundamental ramification of hand injury
      and has been identified as one of the most acutely stressful aspects of traumatic
      injuries and their treatment. Both comorbid psychiatric conditions and
      psychosocial factors have been shown to affect medical treatment outcome in
      patients with hand disorders and pain, further complicating recovery and
      potentially leading to significant psychological, social, and economic
      consequences for the individual. The purpose of this article was to assist hand
      therapists in developing a greater understanding of psychological constructs,
      psychosocial variables, and comorbid psychiatric conditions and thereby
      facilitate the more effective identification of such factors. A case study is
      included to illustrate these concepts. Circumstances in which referral for a
      comprehensive psychological evaluation is necessary are discussed. Many of the
      principles reviewed are also applicable to other upper extremity and
      musculoskeletal conditions.

PMID- 20149960
TI  - Screening for head, neck, and shoulder pathology in patients with upper extremity
      signs and symptoms.
AB  - NARRATIVE REVIEW: Conditions of the head, neck, thorax, and shoulder may occur
      simultaneously with arm pathology or produce symptoms perceived by the patient to
      originate in the elbow, wrist, or hand. Identification of the tissue disorder and
      associated impairments, followed by matching the rehabilitative intervention to
      address these issues, leads to optimal outcomes. With this goal in mind, the hand
      therapist needs to recognize clinical findings that signal potentially serious
      medical conditions of the brain, cervical region, chest, or shoulder.
      Additionally, less serious but potentially debilitating, musculoskeletal or
      neurogenic pain from proximal sources must also be differentiated from somatic
      pain originating in the elbow, wrist, or hand so that the clinician can decide to
      further examine and intervene or refer to an appropriate health care provider.
      This article describes clinical findings that suggest the presence of serious
      medical pathology in the head, neck, or thorax and presents a screening algorithm
      to assist in discriminating pain derived from local structures in the distal arm
      from referred pain originating in the more proximal regions of the shoulder,
      thorax, neck, or brain. LEVEL OF EVIDENCE: 5.

PMID- 20149961
TI  - Sprouting in human temporal lobe epilepsy: excitatory pathways and axons of
      interneurons.
AB  - Changes of hippocampal GABAergic interneuronal circuits are known to play a
      central role in epileptogenesis. Fate of functionally different hippocampal
      interneuron types has been investigated in surgically removed hippocampi of
      therapy resistant human TLE patients. Perisomatic inhibitory cells containing
      parvalbumin are responsible for controlling the output of principal cells.
      Electron microscopic examination revealed that perisomatic innervation of the
      principal cells was preserved in both sclerotic and non-sclerotic samples, and
      the ratio of the initial segment synapses increased among the postsynaptic
      targets, which might give rise to an increased synchrony of granule cell firing.
      Calbindin-containing dendritic inhibitory cells are well preserved, and they
      terminate on other interneurons in larger proportion than in the control both in
      sclerotic and non-sclerotic cases. Substance P receptor-immunopositive cells
      possessed significantly larger numbers of dendritic branches in the epileptic CA1
      region, and the synaptic input of their dendrites has notably increased, whereas
      the ratio of inhibitory and excitatory synaptic inputs has not changed. Our
      results suggest that an intense synaptic reorganization takes place in the
      epileptic hippocampus, including axonal sprouting of certain interneuron types,
      both in sclerotic and non-sclerotic tissue. Thus, axonal sprouting is a more
      general phenomenon of TLE than cell loss.

PMID- 20149962
TI  - Ventilator mode influence survival in noninvasive positive pressure ventilation?

PMID- 20149963
TI  - Abnormalities of plethysmographic lung volumes in asthmatic children.
AB  - BACKGROUND: While lung hyperinflation is frequent in asthma, measurement of lung
      volumes is not recommended in current guidelines. The aim of this descriptive
      functional study was to assess whether systematic measurement of volumes by
      plethysmography may detect isolated hyperinflation with normal expiratory flows.
      METHODS AND PATIENTS: One hundred sixty asthmatic children (mean age + or - SD:
      10.8 + or - 2.7 years; 50 girls) receiving inhaled corticosteroid underwent lung
      function tests before and after bronchodilation (BD). To avoid the problem of
      dysanaptic lung growth on predicted values in childhood, airflow limitation and
      hyperinflation were defined by ratios (FEV(1,%pred)/FVC(%pred) for the former,
      RV/TLC for the latter) and values below and above the 5th or 95th percentiles of
      reference values, were chosen as cut-off values. RESULTS: Different functional
      phenotypes were evidenced, mainly normal lung function (142/160 [89%] after BD),
      but also isolated airflow limitation (35/160 [22%] before and 7/160 [4%] after
      BD) and isolated hyperinflation (17/160 [11%] before and 11/160 [7%] after BD),
      while the combination of both impairments before BD (13/160 [8%]) was never
      observed after BD. There was no statistical relationship between airflow
      limitation and hyperinflation, either before or after BD. Indices of spirometry
      (FEV(1), FEF(50%)) were unable to predict isolated hyperinflation that
      corresponds to small airway obstructive syndrome. CONCLUSION: Isolated
      hyperinflation is not infrequent in asthmatic children (7-11%) and small airway
      obstruction is not detected by forced expiratory flows.

PMID- 20149964
TI  - Landfill leachate affects metabolic responses of Zea mays L. seedlings.
AB  - With an increasing focus on phyto-remediation options for landfill leachate, it
      is important to understand the responses of plant systems to landfill leachate
      stress. It is especially important to study the tolerant mechanisms of plant
      systems. We investigated several physiological changes of Zea mays L. (maize) in
      response to landfill leachate. Specifically, we investigated growth, chlorophyll
      content, lipid peroxidation, protein oxidation and activities of antioxidant
      enzymes. The results indicate that landfill leachate affected the growth and
      chlorophyll level of maize seedlings. Furthermore, landfill leachate elevated the
      levels of lipid peroxidation and protein oxidation in leaf tissues in a time
      dependent manner, accompanied by the changes in antioxidant status. The
      physiological responses varied as a function of leachate concentration, and the
      growth inhibition, chlorophyll content inhibition and oxidative stress occurred
      after the exposure of higher concentrations of leachate. Higher concentrations of
      landfill leachate contained higher levels of pollutants. Our results indicate
      that landfill leachate affected the metabolic responses of plant systems. The
      risk of pollution occurred mainly in samples of higher concentration. Therefore,
      the critical aspect of phyto-remediation for landfill leachate is controlling its
      concentration. In doing so, plant systems may be able to tolerate the
      environmental stress of landfill leachate.

PMID- 20149965
TI  - Effects of local cooling on sacral skin perfusion response to pressure:
      implications for pressure ulcer prevention.
AB  - People with spinal cord injuries are at high risk for developing pressure ulcers.
      Increased skin temperature is one of the extrinsic causative factors for this
      multi-factorial disease. Previous animal studies revealed that local skin cooling
      reduced the severity of ulceration, and cooling is widely used in plastic surgery
      and organ transplants for tissue preservation. The objectives of this pilot study
      were to develop test protocols and instrumentation and to investigate the effect
      of local cooling on skin perfusion response to pressure on young healthy human
      subjects. Reactive hyperemia was quantified in this study to compare the effects
      of pressure with and without cooling. Reactive hyperemia is a normal
      physiological response occurring after vessel occlusion. Laser Doppler flowmetry
      was used to measure skin blood flow. Time-dependent spectral analysis was used to
      analyze and decompose the blood flow data into frequency ranges associated with
      specific blood flow control mechanisms. The study used a repeated measures design
      with two test conditions: 8 kPa of pressure with and without cooling to 25
      degrees C. We hypothesized that local cooling would reduce the post-ischemic
      reactive hyperemic response induced by the rigid indenter. Time series results
      showed that normalized peak perfusion response was significantly lower with
      cooling (p=0.019). Time-dependent spectral analysis results suggested that both
      metabolic and myogenic responses contribute to this protective effect. Findings
      from our study on humans were consistent with previous animal studies. Additional
      studies on individuals with spinal cord injury are planned to further evaluate
      the cooling effect in a high-risk population.

PMID- 20149966
TI  - Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin
      antitumor agents.
AB  - A series of lavendamycin analogues with two, three or four substituents at the C
      6, C-7 N, C-2', C-3' and C-11' positions were synthesized via short and efficient
      methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed
      antitumor agents. The compounds were prepared through Pictet-Spengler
      condensation of the desired 2-formylquinoline-5,8-diones with the required
      tryptophans followed by further needed transformations. Metabolism and toxicity
      studies demonstrated that the best substrates for NQO1 were also the most
      selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor
      cells.

PMID- 20149967
TI  - Validation of a PCR method for the detection of mycoplasmas according to European
      Pharmacopoeia section 2.6.7.
AB  - Recent publication of a revised section for mycoplasma testing in the European
      Pharmacopoeia has led to interest in validating a nucleic acid amplification
      technique (NAT) for use in detection of mycoplasma contaminants in biologics
      drugs. The replacement by or supplementation of the existing culture-based
      methods with a PCR-based method has several advantages for the biopharmaceutical
      industry, mainly with respect to reduced turnaround time for results, and
      potentially lowered cost. Replacement or substitution of existing methods by a
      PCR method requires the demonstration of equivalent assay limit of detection
      (LOD) and specificity. The experimental requirements for this comparability
      validation have been enumerated in detail in the EP section referenced above. In
      this publication, we describe the validation and comparability analysis of a PCR
      method performed exactly according to the EP guidance. Completion of this
      validation activity has resulted in the availability of an assay that meets or
      exceeds EP compliance requirements for a mycoplasma detection method.

PMID- 20149968
TI  - The impact of attrition in an 11-year prospective longitudinal study of younger
      women.
AB  - PURPOSE: To investigate the impact of attrition on prevalence and associations
      between variables across four waves of a longitudinal study. METHODS: Prevalence
      of socio-demographic and health characteristics were estimated for respondents to
      one, two, three or all four waves of the Australian Longitudinal Study of Women's
      Health cohort born between 1973 and 1978. Associations with self-rated General
      Health (GH) and Mental Health (MH) were compared using fixed effects in separate
      mixed models for respondents to at least one wave, at least two waves, at least
      three waves, or four waves of the longitudinal study. RESULTS: 14,247 women aged
      18-23 years responded to Wave 1 in 1996. Respondents to all waves were more
      educated, and less likely to be stressed about money, to be smokers and to have
      children than respondents to some waves. Across all models, better GH was
      consistently associated with more education, no monetary stress, being married,
      having children, fewer visits to the doctor and not smoking. Similar results were
      obtained for MH. CONCLUSIONS: Although the potential for bias due to attrition
      must be considered, the current paper contributes to the growing body of evidence
      that suggests such biases are insufficient to preclude meaningful longitudinal
      analyses.

PMID- 20149969
TI  - Prevalence of overweight and obesity in Italy (2001-2008): is there a rising
      obesity epidemic?
AB  - PURPOSE: To provide national, population-based estimates of the prevalence of
      overweight and obesity in the Italian population. METHODS: Prevalence estimates
      of overweight and obesity were calculated in seven waves (2001-2008) of the cross
      sectional Multipurpose Household Survey organized by the Italian National
      Institute of Statistics, which are representative of the general adult Italian
      population. Sampling weights were used to estimate prevalence figures as well as
      their standard errors. Mean-difference plot was used to evaluate changes in the
      distribution of body mass index across sex and age categories. RESULTS: Almost
      half of Italian men and about 1 of 3 Italian women are overweight or obese.
      Between 2001 and 2008 the age-standardized prevalence of overweight (obesity)
      increased 1.4% (1.9%) in men and 0.4% (0.5%) in women. Mean-difference plots
      showed an upward shift for body mass index distribution with an increasing
      skewness. CONCLUSIONS: The obesity epidemic is one of the major issues in United
      States and other developed countries. However, if for "epidemic" we mean that in
      Italy obesity is steadily increasing, then our data give little support to this
      interpretation. In fact, trends observed between 1983 and 2008 suggest that the
      rates of changes in the prevalence of overweight and/or obesity are not
      increasing.

PMID- 20149970
TI  - Nursing home residence confounds gender differences in Medicare utilization an
      example of Simpson's paradox.
AB  - BACKGROUND: Gender differences in health care utilization in older Americans may
      be confounded by nursing home residence. Medicare data contain several files that
      can be used to create a measure of nursing home residence, but prior work has not
      addressed which best account for potential confounding. Simpson's paradox occurs
      when aggregated data support a different conclusion from what the disaggregated
      data show. We describe such a paradox that appeared when we sharpened our
      definition of "nursing home residence" while examining gender differences in
      Medicare utilization at the end of life. METHODS: To understand gender-specific
      health care utilization at the end of life, we conducted a retrospective analysis
      of a national random sample of Medicare beneficiaries aged 66 or older who died
      in 2001 with Parts A and B data for 18 months before death. We sought to
      associate each of total hospital days and costs during the final 6 months of life
      with numbers of primary care physician visits in the 12 preceding months. In
      addition to demographics, comorbidities, and geography, "nursing home residence"
      was a potential confounder, which we imputed in two ways: 1) from skilled nursing
      facility bills in the Part A Medicare Provider Analysis and Review (MedPAR) file;
      and 2) from Berenson-Eggers-Type-of-Service codes indicating widely spaced doctor
      visits in nursing homes obtained from Medicare's carrier file. CONCLUSION: Gender
      differences in Medicare utilization are strongly confounded by nursing home
      resident status, which can be imputed well from Medicare's carrier file, but not
      MedPAR.

PMID- 20149971
TI  - Multiparity is associated with high motivation to change diet among overweight
      and obese postpartum women.
AB  - BACKGROUND: Pregnancy is associated with weight gain and obesity. The aim of this
      study was to identify the effect of parity and other factors on motivation to
      change diet to lose weight in a cohort of overweight and obese postpartum women.
      STUDY DESIGN: Active Mothers Postpartum is a randomized, controlled trial aimed
      at postpartum weight reduction. At baseline, we measured motivation to change
      diet to lose weight among 491 overweight/obese postpartum women. Logistic
      regression was used to model the effect of parity on motivation to change diet at
      baseline while adjusting for potential confounders including age, race,
      education, body mass index category, and breastfeeding status. RESULTS:
      Approximately two thirds (68%) of participants were highly motivated to change
      their diet to lose weight. In the multivariable model, women with three or more
      children had 2.5 times the odds of high motivation compared with primigravid
      women, and women not breastfeeding had 1.6 times the odds of high motivation
      compared with any breastfeeding. CONCLUSION: Although risk for obesity is
      incurred starting with a woman's first pregnancy, women in this study were more
      motivated to change their diet to lose weight after their third pregnancy.
      Further research is needed to understand how to best capitalize on the high
      motivation in women with several children as well as how to improve motivation
      for primigravid women and women who are breastfeeding.

PMID- 20149972
TI  - The epidemiology of radial head fractures.
AB  - INTRODUCTION: Recent literature shows an increased mean age of female patients
      with radial head fractures compared with male patients with radial head
      fractures. However, data on epidemiology of radial head fractures and
      specifically in relation to age distribution and male-female ratios of radial
      head fracture are scarce. MATERIALS AND METHODS: A retrospective database search
      was performed to identify all patients with a radial head fracture over a 3-year
      period. RESULTS: A total of 328 radial head fractures were diagnosed in 322
      patients. The incidence was 2.8 per 10,000 inhabitants per year. The male-female
      ratio was 2:3. The mean age was 48.0 years (range, 14-88 years; SD, 14.8). The
      mean age of female patients (52.8 years) was significantly higher than that of
      male patients (40.5 years) (P = .001). As the age increases above 50 years, the
      number of female patients becomes significantly higher than the number of male
      patients (P = .001). An associated osseous injury was present in 40 patients
      (12.4%). CONCLUSIONS: Radial head fractures are common, and associated injuries
      are frequent.

PMID- 20149973
TI  - Anteromedial approach for shoulder arthroplasty: current indications,
      complications, and results.
AB  - HYPOTHESIS: The anteromedial approach to the shoulder with detachment of the
      anterior deltoid from its clavicular and anterior acromial origins is a method of
      enhancing exposure for difficult shoulder arthroplasty cases. The aim of this
      study is to describe the current frequency of use, indications, complications,
      and results of this approach. MATERIALS AND METHODS: Between 2000 and 2003, 723
      consecutive shoulder arthroplasties were performed. In 110 (15%) an anteromedial
      approach was used. Patient data; previous surgery; indications for surgery; pain,
      motion, and strength before and after surgery; complications; and the need for
      reoperation were assessed. RESULTS: This approach was used in 9.5% of primary
      cases and 39% of revision cases. Seventy percent had had previous surgery. For
      primary arthroplasty, the most frequent diagnoses were osteoarthritis and the
      sequelae of fractures. In revision cases the most common diagnoses were
      instability and glenoid loosening. The structural indications for the
      anteromedial approach were severe scarring, protection of a frail deltoid,
      improvement in rotator cuff or glenoid exposure, protection of osteopenic bone,
      or enhancement of exposure in oncologic cases or resections. Ninety patients had
      more than 2 years of follow-up. Pain improved after primary and revision
      arthroplasty. Motion only improved in primary arthroplasty. There was little
      change in strength. No proximal deltoid detachments or other approach-related
      complications were identified. CONCLUSIONS: The anteromedial approach is a
      reliable technique to improve surgical exposure in difficult shoulder
      arthroplasty cases. When performed adequately, it can be applied safely without
      anterior deltoid detachment or clinically evident major complications.

PMID- 20149974
TI  - Pegged versus keeled glenoid components in total shoulder arthroplasty.
AB  - HYPOTHESIS: Loosening of the glenoid component is a common complication in
      shoulder arthroplasty. We proposed to radiographically and clinically investigate
      the outcomes of keeled and pegged glenoid components to test the hypothesis that
      these implants would have equivalent performance. MATERIALS AND METHODS: One
      hundred patients undergoing primary shoulder arthroplasty for osteoarthritis were
      reviewed. Fifty patients had pegged glenoid components, and fifty had keeled
      components. Standardized radiographs were taken. Preoperative films classified
      the severity of degenerative change. The postoperative films were analyzed for
      radiolucent lines and shift in component position-at-risk signs for loosening.
      RESULTS: Mean radiographic follow-up was 51.3 months (range, 24-90 months) for
      the keeled group and 45.7 months (range, 27-98 months) for the pegged group.
      There were no differences in the degree of preoperative arthritic change between
      groups. Both groups had significant improvement in motion and pain (P < .001)
      postoperatively, with no differences in clinical outcome between cohorts (P > or
      = .20). Initial radiographs showed no radiolucencies around the pegs in 46
      implants or around the keel in 49 components. At final follow-up, 10 glenoid
      implants were found to be at risk for loosening, 6 (12%) in the pegged group and
      4 (8%) in the keeled group (P = .74). CONCLUSIONS: Initial postoperative
      radiographs with pegged and keeled components show a low rate of radiolucent
      lines. These radiolucencies develop over time. However, there is no difference in
      clinical or radiographic outcomes between pegged and keeled components at
      intermediate-term follow-up.

PMID- 20149975
TI  - Comment on "Hymen-sparing surgery for imperforate hymen: case reports and review
      of literature" by Basaran et al.

PMID- 20149976
TI  - One-trocar, video-assisted stripping technique for use in the treatment of large
      ovarian cysts in infants.
AB  - BACKGROUND: Management of ovarian cysts in infants is controversial; it can be
      conservative or surgical, and the management is determined by the cyst's size and
      sonographic features. METHODS: A surgical approach using a 10-mm umbilically
      placed operative laparoscope was taken in 3 female infants with antenatally
      diagnosed large, simple ovarian cysts. The contents of the cysts were partially
      aspirated and the cyst walls were stripped off the remaining ovarian parenchyma.
      No intraoperative or postoperative complications were recorded. CONCLUSIONS: The
      one-trocar video-assisted stripping technique for large ovarian cysts in infants
      appears to be an ovarian-tissue-preserving procedure, and it sidesteps the
      disadvantages of large scars and formation of adhesions.

PMID- 20149977
TI  - Prenatal smoking among adolescents and risk of fetal demise before and during
      labor.
AB  - STUDY OBJECTIVE: To investigate the relationship between smoking during pregnancy
      and the occurrence of stillbirth phenotypes among adolescent mothers. DESIGN:
      Retrospective cohort SETTING: Singleton births in Missouri from 1978 through
      1997. PARTICIPANTS: Two groups of "younger" (<15 years) and "older" (15-19 years)
      adolescent mothers were compared to "mature" mothers (age 20-24 years). MAIN
      OUTCOME MEASURES: Cox Proportional Hazards Regression models generated adjusted
      risk estimates of the association between intrauterine nicotine exposure and the
      risk of total, antepartum, and intrapartum stillbirth in each age group. RESULTS:
      Approximately 32% (N=205,887) of the total 633,849 singleton births analyzed were
      among adolescent mothers. The overall prevalence of smoking was 31.2%, with the
      lowest prevalence (14.1%) among the youngest mothers while older adolescents had
      the highest (31.7%). The risk for intrapartum stillbirth among smoking
      adolescents <15 years of age was twice the risk for older adolescent and mature
      mothers. The risk of intrapartum stillbirth among smokers decreased as maternal
      age increased: [adjusted hazard ratio (AHR), 95% confidence interval (CI) for
      young mothers: 4.0, 95%CI=0.6-28.7; for older adolescents AHR=1.5, 95%CI=1.1-2.1
      and for mature mothers AHR=1.8, 95% CI=1.4-2.2], respectively. CONCLUSIONS: In
      utero tobacco exposure has maternal age-related differential and lethal effects
      on the fetus. Young maternal age tends to potentiate these effects. There is a
      public health need to develop appropriate smoking cessation messages targeted
      specifically to this high risk group.

PMID- 20149978
TI  - Fine-needle aspiration may replace skin biopsy for the collection of material for
      experimental infection of mice with Mycobacterium leprae and Lacazia loboi.
AB  - BACKGROUND: Procedures involving the use of Mycobacterium leprae and Lacazia
      loboi, uncultivated organisms, depend on the collection of material from the
      lesions of patients or experimental animals. This study compared fine-needle
      aspiration (FNA) and skin biopsy methods for obtaining bacilli and fungal cells
      to experimentally infect animals. METHODS: Lepromas from one armadillo and one
      enlarged footpad of a mouse previously inoculated with L. loboi were submitted to
      FNA and biopsy. Materials collected were processed for inoculation in mice.
      RESULTS: Acid-fast bacilli (AFB) collected by two FNA procedures yielded
      7.2*10(7) and 5.3*10(6) AFB/ml and biopsies yielded 1.58*10(8) and 3.5*10(8)
      AFB/ml from each leproma. Yeast-like cells of L. loboi collected by FNA yielded
      1.0*10(6) fungal cells/ml and biopsy 1.0*10(7) fungal cells/ml. After 8 months,
      inoculated animals were sacrificed and the inoculated footpads submitted to
      histopathological examination and counting of AFB and fungal cells. The results
      obtained by the two methods were comparable for both microorganisms. CONCLUSIONS:
      Biopsy may be replaced by FNA during harvesting of material for different
      purposes, especially for experimental inoculation of mice in leprosy and Jorge
      Lobo's disease, with the advantage of FNA being a simpler, less invasive, and
      less costly method.

PMID- 20149979
TI  - Pelagodinium gen. nov. and P. beii comb. nov., a dinoflagellate symbiont of
      planktonic foraminifera.
AB  - The taxonomic status of the free-living stage of the dinoflagellate Gymnodinium
      beii, symbiont of the foraminifer Orbulina universa, was reassessed on the basis
      of detailed morpho-genetic analyses. Electron microscopy observations revealed
      previously undescribed morphological features of the cell that are important for
      species recognition. The presence of a single elongated apical vesicle (EAV)
      ornamented with a row of small knobs, absent in species of the genus Gymnodinium,
      calls into question the current taxonomic position of the symbiont. The presence
      of a type E extraplastidial eyespot, the arrangement of the amphiesmal vesicles
      in series and the absence of trichocysts confirm the affiliation with other
      symbiotic dinoflagellates and certain genetically related non-symbiotic genera,
      all belonging to the order Suessiales. The arrangement of the series of vesicles
      of the analyzed strain is unique within the Suessiales, and the ultrastructure of
      the pyrenoid is different from other symbiotic dinoflagellates. A large subunit
      (LSU) rDNA phylogenetic analysis confirmed that the analyzed pelagic symbiont
      clusters in an independent, well-supported clade within the Suessiales with other
      sequences of symbiotic dinoflagellates extracted from planktonic foraminifera.
      Hence a novel genus, Pelagodinium gen. nov., is erected for this pelagic,
      symbiotic dinoflagellate, and Gymnodinium beii is reclassified as Pelagodinium
      beii.

PMID- 20149980
TI  - Initial experience with percutaneous selective embolization: A truly minimally
      invasive treatment of the adolescent varicocele with no risk of hydrocele
      development.
AB  - OBJECTIVE: Postoperative hydrocele development is a frustrating complication of
      varicocele surgical repair. To avoid this complication, we began to offer
      percutaneous embolization as a treatment option. We present our initial
      experience with this technique. METHODS: A retrospective review of all patients
      who underwent percutaneous embolization and sclerotherapy of a varicocele at our
      institution was performed. RESULTS: There were 27 patients with a mean age of 16
      years (range 13-19 years). Indications included pain (48%), varicocele size (30%)
      and persistent testicular asymmetry (22%). Four patients had experienced failure
      of a previous surgical repair. Follow-up data were available for 21 patients
      (mean 9 months). The varicocele resolved in 19 patients (91%) with no evidence of
      hydrocele formation in any of the boys. There was resolution of pain in all
      patients for whom this was the indication for the procedure. In the two failures,
      access to the lower spermatic vein was not possible owing to the number and
      tortuosity of the vessels. CONCLUSIONS: Percutaneous embolization and
      sclerotherapy represent a truly minimally invasive treatment with low morbidity,
      minimal pain and rapid recovery. In our early experience, since lymphatic
      channels are completely avoided, there appears to be no risk of hydrocele
      formation.

PMID- 20149981
TI  - Evaluation of radiobiologic biochemical control in a large permanent prostate
      brachytherapy population from a single institution using AAPM TG-137 parameters.
AB  - PURPOSE: To re-evaluate prostate implant dosimetry using American Association of
      Physicists in Medicine Task Group 43 parameters and the radiobiologic approach of
      American Association of Physicists in Medicine Task Group 137. METHODS AND
      MATERIALS: Among 1473 consecutive patients implanted with iodine-125 or palladium
      103 sources before March 2006, there have been 55 biochemical failures. The
      dosimetric quality parameter, D(90), was updated according to the radionuclide
      and dosimetric era of the implant. For each patient, biologically equivalent dose
      (BED) and tumor control probability (TCP) were calculated from the updated
      implant D(90) plus any external beam dose using recommended indices and
      equations. RESULTS: There was no significant difference in BED between
      biochemical failures and nonfailures, 148+/-27Gy and 145+/-24Gy, respectively
      (p=0.352). TCP was 0.90+/-0.26 for biochemical failures and 0.93+/-0.21 for
      nonfailures (p=0.414). Cox regression analysis found that neither BED nor TCP
      predicted for biochemical control either for the entire population or within each
      radionuclide-dependent dosimetric era. The only overall predictors of biochemical
      control were dosimetric era, Gleason score, and percent positive biopsies.
      Improvements in dosimetric quality over the first 300 patients were evident, but
      dosimetric era remained a better predictor of biochemical outcome than implant
      sequence number. CONCLUSION: In a large prostate implant population, dosimetric
      and derived radiobiologic parameters did not predict for failure. Apparently, too
      few patients had total BEDs below the level necessary for optimum biochemical
      control. A learning curve extended over hundreds of patients before plateauing
      but changes in seed characterization parameters also had a pronounced effect.

PMID- 20149982
TI  - Unusual failure of a multilumen, small-diameter implantable cardioverter
      defibrillator lead.

PMID- 20149983
TI  - The treatment of chronic hepatitis C virus infection in HIV co-infection.
AB  - Chronic HCV co-infection is present in up to one third of HIV-positive patients
      in Europe. In recent years, apart from the traditional transmission route of
      intravenous drug abuse, outbreaks of sexually transmitted acute HCV infections,
      mainly among HIV-positive men who have sex with men, have contributed to the
      overall disease burden. - Because the natural course of HCV infection is
      substantially accelerated in HIV-co-infection, end-stage liver disease has become
      the most frequent cause of non-AIDS related death in this population. Therefore
      every HIV/HCV co-infected patient should be evaluated for possible anti-HCV
      therapy with the goal of reaching a sustained virological response and thus cure
      of hepatitis C infection. The standard of care for the treatment of chronic HCV
      infection in HIV-infected remains a pegylated interferon in combination with
      weight-adapted ribavirin. - HAART should not be withheld from HCV co-infected
      patients due to concerns of drug related hepatotoxicity and in patients with
      reduced CD4-cell counts HAART should be started first. Under pegylated interferon
      and ribavirin combination therapy drug to drug interactions and cumulated
      toxicity between nucleoside analogues and anti-HCV therapy may be observed and
      concomitant didanosine use is contraindicated and zidovudine and stavudine should
      be avoided if possible. - The development of new drugs for the treatment of
      chronic hepatitis C represents a promising perspective also for HIV positive
      patients. However, these substances will probably reach clinical routine for HIV
      patients later than HCV monoinfected patients. Therefore at present waiting for
      new drugs is not an alternative to a modern pegylated interferon/ribavirin
      therapy.

PMID- 20149984
TI  - Long-term efficacy and safety of once-daily nevirapine in combination with
      tenofovir and emtricitabine in the treatment of HIV-infected patients: a 72-week
      prospective multicenter study (TENOR-trial).
AB  - BACKGROUND: There is an unmet medical need for simplified antiretroviral therapy
      regimens to improve patient's compliance and quality of life. The purpose of this
      study was to evaluate the efficacy and safety of a once-daily regimen with
      Tenofovir (TDF), Emtricitabine (FTC) and Nevirapine (NVP) for adult patients with
      HIV-1 infection. METHODS: 70 patients were enrolled in a prospective,
      multicenter, non-randomized, single arm, open-label cohort study. Patients were
      either naive or had problems with their current ART and needed to be changed to
      another regimen. Daily drug dosage was 300 mg Tenofovir, 200mg Emtricitabine and
      400 mg Nevirapine once daily. Follow-up was performed over 72 weeks. RESULTS:
      After 72 weeks, the regimen was still continued by 52 patients (74,3%). Of these,
      44 patients (84,6%) had a viral load below detection limit. The median viral load
      had decreased by 2,5 log and the median CD4 cell count had increased by 44,8%.
      Most side-effects occurred at an early stage during the study. Resistances were
      rare (only two resistances were considered as newly developed) and occurred
      rather late during the study. CONCLUSION: A once-daily regimen of Tenofovir,
      Emtricitabine and Nevirapine is an attractive treatment option since it is safe,
      effective, and well tolerated.

PMID- 20149985
TI  - Renin, endothelial NO synthase and endothelin gene expression in the 2kidney
      1clip Goldblatt model of long-term renovascular hypertension.
AB  - OBJECTIVE: Numerous reports have shown the influence of renin, nitric oxide (NO)
      and the endothelin (ET) systems for regulation of blood pressure and renal
      function. Furthermore, interactions between these peptides have been reported.
      Aim of our study was to investigate the relative contribution of these compounds
      in long-term renovascular hypertension / renal ischemia. METHODS: Hypertension /
      left-sided renal ischemia was induced using the 2K1C-Goldblatt rat model. Renal
      renin, ET-1, ET-3 and endothelial NO synthase (eNOS) gene expression was measured
      by means of RNAse protection assay at different timepoints up to 10 weeks after
      induction of renal artery stenosis. RESULTS: Plasma renin activity and renal
      renin gene expression in the left kidney were increased in the clipped animals
      while eNOS expression was unchanged. Furthermore, an increase in ET-1 expression
      and a decrease of ET-3 expression was detected in early stenosis. CONCLUSIONS:
      While renin is obviously involved in regulation of blood pressure and renal
      function in unilateral renal artery stenosis, ET-1, ET-3 and endothelium derived
      NO do not appear to play an important role in renal adaptation processes in long
      term renal artery stenosis, although ET-1 and ET-3 might be involved in short
      term adaptation processes.

PMID- 20149986
TI  - Serum heparan sulfate levels are elevated in endotoxemia.
AB  - BACKGROUND: Increased vascular permeability is a characteristic feature of sepsis
      which, in the past, has been ascribed exclusively to a malfunction of endothelial
      cells. However, recently it has become evident that the endothelial glycocalyx is
      of considerable importance concerning various aspects of vascular physiology,
      e.g. the vascular barrier and inflammation. Heparan sulfate, one of its essential
      components is characteristically traceable in blood, in case the endothelial
      glycocalyx is damaged or destroyed. METHODS: In 15 pigs we investigated whether
      the administration of endotoxin from gram-negative bacteria (Escherichia coli)
      results in increased serum levels of heparan sulfate, signalizing a shedding of
      the glycocalyx. In addition, markers of inflammation (white blood cell count,
      platelet count, tumour necrosis factor-alpha and interleukin-6) were evaluated
      over an observation period of 6 hours. RESULTS: Serum heparan sulfate
      concentrations significantly increased over time in the endotoxin group and were
      significantly elevated in comparison to the control group 6 hours after
      administration of endotoxin (p<0.001). In the endotoxin group all markers of
      inflammation significantly changed during the time course. CONCLUSIONS: The
      administration of bacterial endotoxin induced a significant rise in degradation
      products of the endothelial glycocalyx.

PMID- 20149988
TI  - When the heart kills the liver: acute liver failure in congestive heart failure.
AB  - Congestive heart failure as a cause of acute liver failure is rarely documented
      with only a few cases. Although the pathophysiology is poorly understood, there
      is rising evidence, that low cardiac output with consecutive reduction in hepatic
      blood flow is a main causing factor, rather than hypotension. In the setting of
      acute liver failure due to congestive heart failure, clinical signs of the latter
      can be absent, which requires an appropriate diagnostic approach. As a reference
      center for acute liver failure and liver transplantation we recorded from May
      2003 to December 2007 202 admissions with the primary diagnoses acute liver
      failure. 13/202 was due to congestive heart failure, which was associated with a
      mortality rate of 54%. Leading cause of death was the underlying heart failure.
      Asparagine transaminase (AST), bilirubin, and international normalized ratio
      (INR) did not differ significantly in surviving and deceased patients at
      admission. Despite both groups had signs of cardiogenic shock, the cardiac index
      (CI) was significantly higher in the survival group on admission as compared with
      non-survivors (2.1 L/min/m(2) vs. 1.6 L/min/m(2), p=0.04). Central venous - and
      pulmonary wedge pressure did not differ significantly. Remarkable improvement of
      liver function was recorded in the group, who recovered from cardiogenic shock.
      In conclusion, patients with acute liver failure require an appropriate
      diagnostic approach. Congestive heart failure should always be considered as a
      possible cause of acute liver failure.

PMID- 20149987
TI  - Duration and predictors of emergency surgical operations--basis for medical
      management of mass casualty incidents.
AB  - BACKGROUND: Hospitals have a critically important role in the management of mass
      causality incidents (MCI), yet there is little information to assist emergency
      planners. A significantly limiting factor of a hospital's capability to treat
      those affected is its surgical capacity. We therefore intended to provide data
      about the duration and predictors of life saving operations. METHODS: The data of
      20,815 predominantly blunt trauma patients recorded in the Trauma Registry of the
      German-Trauma-Society was retrospectively analyzed to calculate the duration of
      life-saving operations as well as their predictors. Inclusion criteria were an
      ISS>=16 and the performance of relevant ICPM-coded procedures within 6h of
      admission. RESULTS: From 1,228 patients fulfilling the inclusion criteria 1,793
      operations could be identified as life-saving operations. Acute injuries to the
      abdomen accounted for 54.1% followed by head injuries (26.3%), pelvic injuries
      (11.5%), thoracic injuries (5.0%) and major amputations (3.1%). The mean cut to
      suture time was 130min (IQR 65-165min). Logistic regression revealed 8 variables
      associated with an emergency operation: AIS of abdomen >=3 (OR 4,00), ISS >=35
      (OR 2,94), hemoglobin level <=8 mg/dL (OR 1,40), pulse rate on hospital admission
      <40 or >120/min (OR 1,39), blood pressure on hospital admission <90 mmHg (OR
      1,35), prehospital infusion volume >=2000 ml (OR 1,34), GCS <=8 (OR 1,32) and
      anisocoria (OR 1,28) on-scene. CONCLUSIONS: The mean operation time of 130min
      calculated for emergency life-saving surgical operations provides a realistic
      guideline for the prospective treatment capacity which can be estimated and
      projected into an actual incident admission capacity. Knowledge of predictive
      factors for life-saving emergency operations helps to identify those patients
      that need most urgent operative treatment in case of blunt MCI.

PMID- 20149989
TI  - Interpretation of non-invasive breath tests using (13)C-labeled substrates--a
      preliminary report with (13)C-methacetin.
AB  - Non-invasive breath tests can serve as valuable diagnostic tools in medicine as
      they can determine particular enzymatic and metabolic functions in vivo. However,
      methodological pitfalls have limited the actual clinical application of those
      tests till today. A major challenge of non-invasive breath tests has remained the
      provision of individually reliable test results. To overcome these limitations, a
      better understanding of breath kinetics during non-invasive breaths tests is
      essential. This analysis compares the breath recovery of a (13)C-methacetin
      breath test with the actual serum kinetics of the substrate. It is shown, that
      breath and serum kinetics of the same test are significantly different over a
      period of 60 minutes. The recovery of the tracer (13)CO(2) in breath seems to be
      significantly delayed due to intermediate storage in the bicarbonate pool. This
      has to be taken into account for the application of non-invasive breath test
      protocols. Otherwise, breath tests might display bicarbonate kinetics despite the
      metabolic capacity of the particular target enzyme.

PMID- 20149990
TI  - Partial anomalous pulmonary venous return associated with coarctation of the
      aorta.

PMID- 20149991
TI  - Triple right coronary artery accompanied by an ectopic circumflex artery arising
      from right sinus of Valsalva.

PMID- 20149992
TI  - Takotsubo cardiomyopathy mimicking acute high lateral myocardial infarction.

PMID- 20149993
TI  - [A case of infective endocarditis presented with a giant free wall vegetation].

PMID- 20149994
TI  - Pulmonary stenosis due to metastatic malignant melanoma.

PMID- 20149995
TI  - [Preparation of AKD for the second decade].

PMID- 20149996
TI  - Anatomic variability of the coronary arterial orifices.
AB  - OBJECTIVE: Anatomical differences in coronary orifices (CO) are important as they
      are associated with myocardial ischemia and sudden death. The location of
      coronary orifices to the aortic valve has been studied since it is a determining
      point in surgical and radiological attempts. METHODS: The number, position, and
      shape of the CO, and their relation to the sinotubular junction (SJ), were
      studied in 100 normal adult hearts. Student-t test, one- and two-way ANOVA with
      posthoc Tukey's HSD tests were applied for statistical analysis. RESULTS: The
      mean height of the right, non- and left coronary sinuses were 18.75+/- 1.71,
      17.86+/- 1.55 and 16.41+/- 1.21 mm, respectively. The mean height of the right,
      non- and left coronary cusps were measured as 16.2+/- 1.2, 15.9+/- 1.1 and 12.3+/
      2.1 mm, respectively. The left coronary artery (LCA) was observed to arise from
      the lower part of the SJ in 58% of the patients, while in 29% of them it
      originated from the SJ, and in 13% of the cases it arose from the upper part of
      the SJ. The right coronary artery (RCA) arising from the lower part of the SJ was
      seen in 78% of the patients, while it originated from the SJ in 13% of the
      patients, and it was observed to arise from the upper part of the SJ in 9
      specimens. The diameters of the LCA and RCA were measured as 4.22+/- 0.72 and
      3.32+/- 0.82 mm, respectively. An accessory orifice was found on the left in 47
      specimens, while it was seen on the right in 54 of them. CONCLUSIONS: The
      location of the CO should be identified according to the vertical and horizontal
      surfaces of the sinus. In this study, the frequency of the coronary artery
      orifices with different locations was provided. Such data will increase the
      success of coronary interventions and decrease complication rate.

PMID- 20149997
TI  - Importance of anatomic variability of the coronary arterial orifices.

PMID- 20149998
TI  - Inhibitory effects of ticlopidine and clopidogrel on the intimal hyperplastic
      response after arterial injury.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of ticlopidine
      and clopidogrel on the development of neointimal hyperplasia after experimental
      arterial injury. METHODS: This experimental, prospective, randomized controlled
      study was performed on twenty-seven rabbits, which were divided into three
      groups, each of which contained nine subjects. Following the development of a
      balloon catheter injury in the iliac artery, no drugs were administered to Group
      1 (control). Group 2 was given ticlopidine, while Group 3 was given clopidogrel.
      At the end of the 21-day experimental period, arterial sections were evaluated
      histomorphologically and immunohistochemically with staining using antibodies
      against platelet derived growth factor beta and basic fibroblast growth factor.
      Statistical analyses were performed using Chi-Square, Mann Whitney U and one-way
      ANOVA tests. RESULTS: At the end of study period, ticlopidine and clopidogrel
      strongly reduced the development of intimal hyperplasia after arterial injury
      (54.1%, p<0.001, 53.2%, p<0.001, respectively). No significant difference was
      observed in terms of intimal and medial areas between the drug-treated groups.
      Expressions of the basic fibroblast growth factor and platelet derived growth
      factor beta were significantly lower in the intima of drug treated groups with
      respect to the control group (p<0.05). CONCLUSION: The results of our study
      suggest that ticlopidine and clopidogrel, which are widely used in antiplatelet
      treatment in clinics, can similarly prevent the development of intimal
      hyperplasia after experimental arterial injury.

PMID- 20149999
TI  - Antiplatelet therapy with clopidogrel or ticlopidine reduces intimal hyperplasia
      in an animal model of experimental arterial injury.

PMID- 20150000
TI  - Nebivolol prevents remodeling in a rat myocardial infarction model: an
      echocardiographic study.
AB  - OBJECTIVE: Ventricular remodeling (VR) which develops after myocardial infarction
      (MI) plays an important role in progressive left ventricular dysfunction. We
      aimed to investigate the role of nebivolol treatment on VR after a MI in a rat
      ischemia-reperfusion model. METHODS: Rats were divided into 3 groups of 12 each:
      sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI
      nebivolol). Left ventricular (LV) diameters, volumes, and diastolic filling
      parameters were evaluated by echocardiography. On the 28th day, after recording
      the systemic and LV pressures and determining the plasma nitric oxide (NO) and
      peroxynitrite (ONOO-) levels , animals were sacrificed and heart, body and LV
      weights (HW, BW, LVW) were measured and infarct sizes were determined. Results
      were evaluated statistically by ANOVA for repeated measurements 3x3 factorial
      design with post-hoc Bonferroni test. RESULTS: After MI, while VR (an increase in
      LV diameters and volumes associated with a decrease in EF, FS and posterior wall
      thickness change (LWPc) was significant in MI-control rats (p<0.05 for; all
      comparisons) these changes were significantly less in MI-nebivolol group (p=0.08
      and p=0.06 for EF and FS respectively). LV end diastolic pressure (LVEDP) was
      lower (p<0.005) and Delta+/- dp/dt's (p<0.05) were higher in MI-nebivolol group
      compared to MI-control animals. Although infarct sizes were similar in MI-induced
      groups (p=0.79); LVW/HW and HW/BW's were significantly greater in the MI-control
      group compared to sham-control (p<0.01 for all comparisons), these changes were
      not statistically significant in MI-nebivolol group. The increase in plasma NO
      and ONOO- levels were also prevented with nebivolol. CONCLUSION: Nebivolol
      therapy reduced the effects of VR in rats after MI. These beneficial effects were
      not related to its heart rate and blood pressure reducing effects. Nitric oxide
      regulatory action of this compound may contribute these beneficial effects on VR
      developed after MI.

PMID- 20150001
TI  - Hazelnut consumption decreases the susceptibility of LDL to oxidation, plasma
      oxidized LDL level and increases the ratio of large/small LDL in normolipidemic
      healthy subjects.
AB  - OBJECTIVE: Nut consumption has beneficial effects on protection for development
      of atherosclerotic process. METHODS: Single intervention study design was used to
      determine the effects of hazelnut-enriched diet (1 g/kg/day) during 4 weeks
      period on atherogenic tendency of low-density lipoprotein (LDL) by evaluating
      susceptibility of LDL to oxidation, alpha-tocopherol content of LDL, LDL
      subfractions, plasma oxidized (ox) LDL, lipid and lipoprotein levels in
      normolipidemic healthy subjects (n=21). Statistical analysis was performed using
      paired t test, ANOVA for repeated measurements test, Pearson's and Spearman
      correlation analyses. RESULTS: Lag time for oxidation (baseline 54.6+/- 12.3 min,
      15th day 59.3+/- 13.4 min, 30th day 65.2+/- 17.8 min, p=0.001) and ,alpha-
      tocopherol content of LDL (baseline 4.82+/- 1.2 microg/mg LDL protein, 15th day
      4.88+/- 1.4 microg/mg LDL protein, 30th day 5.35+/- 1.7 microg/mg LDL protein,
      p=0.02) were found to be increased while ox-LDL levels (baseline 57.2+/- 16.2
      U/L, 15th day 51.2+/- 13.6 U/L, 30th day 48.2+/- 14.2 U/L, p=0.001) decreased
      during the study period. Total cholesterol, LDL-cholesterol, apolipoprotein (apo)
      B and apo B/apo AI ratio were found to be significantly lower while apo AI was
      higher (p<0.05). In respect to LDL subfraction, ratio of large/small LDL was
      significantly increased at the end of the study (baseline 3.79+/- 1.35, 15th day
      3.41+/- 1.60, 30th day 4.28+/- 2.44, p= 0.046). CONCLUSION: Hazelnut-enriched
      diet may play important role in decrease in atherogenic tendency of LDL by
      lowering the susceptibility of LDL to oxidation and plasma ox-LDL levels, and
      increasing the ratio of large/small LDL beyond its beneficial effect on lipid and
      lipoprotein levels.

PMID- 20150002
TI  - Management and comorbidities of atrial fibrillation in patients admitted in
      cardiology service in Kosovo-a single-center study.
AB  - OBJECTIVE: Atrial fibrillation (AF) is the most important risk factor for
      ischemic stroke. Anticoagulation therapy can substantially decrease the risk of
      stroke in patients with AF. The aim of our study was to investigate the patient's
      comorbidities and management of patients with AF on the discharge. METHODS: From
      5382 consecutive patients admitted in our institution between January 2005 and
      March 2008, 525 (mean age 66.4+/- 11.4 years, 53.3% male) had AF upon discharge,
      who were included in this retrospective study. Patients were divided in two
      groups according to prescription of anticoagulation therapy at discharge.
      Continuous data were compared between groups using a two-tailed unpaired Student
      t test. Discrete variables were compared using Chi-square test or Fisher's exact
      probability test as appropriate. Logistic regression analysis was used to
      identify the independent clinical and echocardiographic predictors of prescribing
      oral anticoagulation therapy. RESULTS: Associated comorbidities of AF in our
      patients were: ischemic heart disease (21.4%), hypertensive heart disease
      (27.44%), valvular heart disease (17.4%), congestive heart failure (47%), chronic
      obstructive pulmonary disease (6.7%), and diabetes 14.3%). Of 525 patients 76%
      were discharged on beta-blockers, 67% on angiotensin converting enzyme
      inhibitors, 23% on digoxin, 16% on calcium antagonists, 67% on diuretics, 72% on
      aspirin, and 27% on oral anticoagulant (OAC) therapy, 11% were with both
      antithrombotics. Multivariate analysis showed that the under-prescription of OAC
      therapy in patients with AF was independently associated with elder age
      (OR=0.916, 95%CI 0.891-0.942, p<0.001), non-enlarged left atrium (OR=1.148, 95%CI
      1.100-1.198, p<0.001) and good left ventricular ejection fraction (OR=0.970,
      95%CI 0.948-0.993, p=0.011). CONCLUSIONS: Patients with atrial fibrillation were
      mainly with ischemic, hypertensive heart disease and congestive heart failure.
      Our study, suggests underuse of anticoagulation therapy. The independent
      predictors of under prescription of anticoagulants in patients with atrial
      fibrillation were elder age, non-enlarged left atrium, and good left ventricular
      ejection fraction. Medical treatment with other groups of drugs for atrial
      fibrillation and comorbidities seems to be according to current guidelines.

PMID- 20150003
TI  - Oral anticoagulation in atrial fibrillation: are the problems solved?

PMID- 20150004
TI  - Comparative effects of losartan and nifedipine therapy on exercise capacity,
      Doppler echocardiographic parameters and endothelin levels in patients with
      secondary pulmonary hypertension.
AB  - OBJECTIVE: Pulmonary hypertension (PHT) is associated with high mortality and
      morbidity. Interest has increased in the use of drugs that, because of their
      neurohumoral inhibitory effects, inhibit the renin angiotensin system. In this
      study, we sought to examine whether losartan therapy is non-inferior to
      nifedipine in the treatment of secondary PHT. METHODS: This prospective
      randomized study consisted of 63 patients (mean age, 63.7+/- 9.1 years) with PHT
      who underwent Doppler echocardiographic examination. A baseline 6-minute walk
      test (6MWT) and cardiopulmonary exercise test (CPET) were performed, and the
      endothelin-1 level of each patient was measured. Patients were assigned to two
      groups receiving treatment with nifedipine (n=30) and losartan (n=33). After 2
      months of treatment, those measurements were repeated. The groups were compared
      with regard to effectiveness for the studied parameters using 2*2 factorial ANOVA
      design for repeated measurements. RESULTS: When posttreatment values were
      compared with baseline values in both groups, the following statistically
      significant changes were noted: the mean values of both mean and systolic
      pulmonary artery pressures (PAPs) were reduced (p<0.05) on Doppler
      echocardiography; exercise duration, work rate, and end-tidal carbon dioxide
      pressure (PETCO2) were higher (p<0.05 for all); and the minute ventilation (VE)
      and ventilatory equivalents for carbon dioxide (VE/VCO2) were lower (p<0.05 for
      both) according to the results of a CPET. No statistically significant change was
      noted in the mean levels of serum endothelin-1. With regard to the results cited
      above, no statistically significant difference was detected between the losartan
      and nifedipine groups (p>0.05). CONCLUSION: The findings of this study indicate
      that losartan is non-inferior to nifedipine for reducing PAP and improving
      exercise capacity. However, the short-term use of losartan or nifedipine had no
      statistically significant effect on endothelin-1 levels in patients with
      secondary PHT.

PMID- 20150005
TI  - Losartan and nifedipine therapy in patients with secondary pulmonary
      hypertension.

PMID- 20150006
TI  - Carotid intima-media thickness and its relations with the complications in
      patients with type 1 diabetes mellitus.
AB  - OBJECTIVE: Atherosclerosis is the major cause of the morbidity and mortality in
      type 1 diabetes mellitus (DM). Carotid intima-media thickness (CIMT) is the early
      sign of atherosclerosis and thereby, also the sign of macrovascular diseases. In
      this study, we aimed to evaluate the CIMT in patients with type 1 DM, and its
      association with diabetic microvascular complications (nephropathy-retinopathy).
      METHODS: One hundred and thirteen consecutive patients with type 1 DM without
      macrovascular disease were enrolled into this cross-sectional study. Age, gender,
      and body mass index matched 59 healthy subjects, were taken as the control group.
      Microvascular complications in diabetic patients were scanned. Ultrasonographic
      analysis of the carotid artery was performed with a high-resolution ultrasound
      scanner. Student's t, Mann Whitney U, Chi-square and Kruskal-Wallis tests, as
      well as multiple linear regression analysis were used for the statistical
      analysis. RESULTS: Patients with type 1 DM had significantly higher CIMT compared
      to control group (p<0001). The CIMT of the patients with microvascular
      complications (nephropathy and/or retinopathy) was significantly increased
      (0.70+/-0.11 mm) compared with the patients without complications (0.63+/-0.09
      mm) (p=0.001). The increase in CIMT in type 1 DM in multiple regression analysis
      was dependent on the presence of proliferative retinopathy (beta=0.037, 95%CI
      0.010-0.065, p=0.008), macroalbuminuria (beta=0.043, 95%CI 0.019-0.068, p=0.001),
      increased urinary albumin excretion (beta=0.00003, 95%CI 0.00001-0.00005,
      p=0.005) and duration of diabetes (beta=0.002, 95%CI 0.001-0.003, p=0.009).
      CONCLUSIONS: Increment of CIMT in type 1 diabetic patients was associated with
      microvascular complications, suggesting that diabetic microangiopathy is related
      with macroangiopathy. Therefore, there is a need for prospective studies to show
      the effect of increased CIMT on prognosis of type 1 DM.

PMID- 20150007
TI  - Carotid intima-media thickness in type 1 diabetes mellitus.

PMID- 20150008
TI  - Percutaneous renal artery stenting reduces arterial blood pressure, but what
      about renal function? A single-center experience.
AB  - OBJECTIVE: To assess the effects of percutaneous transluminal angioplasty and
      stenting (PTRA/S) on arterial blood pressure and renal function. METHODS: A
      retrospective chart review of patients undergoing PTRA/S at our institution
      between December 2003 and September 2006 was done. Follow-up data were derived
      from hospital records. Estimated glomerular filtration rate (EGFR) was used as
      the marker of renal function. To evaluate the pre- and post-procedure values in
      individual patients the paired t test and Wilcoxon signed-rank tests were used.
      RESULTS: Thirty-six patients (16 women, 30 men; mean age 59+/-15 years, range: 25
      83 years) underwent 43 PTRA/S interventions at our institution. The mean duration
      of follow-up was 9.3+/-8.6 (range 2-28) months. We observed no significant change
      in EGFR from pre-procedure to that obtained at follow-up (71.4+/-40.2 mL/min
      vs.73.3+/-39.0 mL/min; p=0.483). Mean arterial blood pressure (MABP), however,
      was reduced significantly: pre-procedure MABP-123+/-22 mmHg; post-procedure
      follow-up value of 101+/-14 mmHg (p<0.001). The mean number of antihypertensive
      medications used at the time of intervention was 2.1+/-1.0 (range: 0-4), whereas
      at follow-up, this number had decreased to 1.3+/-1.0 (range: 0-4; p<0.001). In
      patients with renal impairment (EGFR < or =59 mL/min), 41% showed improvement,
      29% showed no change and 29% demonstrated deterioration in EGFR. CONCLUSION:
      PTRA/S may preserve renal function, especially in patients with pre-procedural
      impaired renal function.

PMID- 20150009
TI  - Renal stenting: still alive after ASTRAL and STAR publications?

PMID- 20150010
TI  - Assessment of cardiac masses: magnetic resonance imaging versus transthoracic
      echocardiography.
AB  - OBJECTIVE: The purpose of this study is to compare the role of magnetic resonance
      imaging (MRI) with transthoracic echocardiography (TTE) for characterization of
      cardiac masses. METHODS: Twenty-three patients were examined with a 1.5T MRI
      Scanner and TTE for the evaluation of suspected intracardiac masses. MRI
      examinations were performed with a protocol of steady cine imaging, HASTE and 3D
      IR-FLASH sequence after administration of gadolinium chelate. All patients were
      examined with MRI within a period of 1-2 weeks after TTE. RESULTS: According to
      the results of MRI, 15 patients underwent cardiac surgery. All of the operated
      patients were proven to have cardiac tumors with no false positive diagnosis on
      MRI. In 3 of 8 unoperated patients who were diagnosed to have cardiac tumors on
      TTE, cardiac thrombi were identified on MRI. Two patients with Eustachian valve
      in the right atrium on MRI were misinterpreted as having cardiac masses on TTE.
      In one patient with known renal cancer, metastases were diagnosed within the
      myocardium on MRI. TTE demonstrated a mass in the left atrium in one patient with
      a history of myxoma operation, whereas MRI was able to show the paracardiac
      extension of the mass into pulmonary veins and lung metastases, which are
      indicators of malignant transformation. In one patient, a mediastinal mass
      compressing the left atrium on MRI was misinterpreted as an intracavitary lesion
      with TTE. CONCLUSION: Contrast enhanced MRI is a noninvasive method superior to
      TTE in diagnosis, differentiation, and detection of extension of cardiac masses.

PMID- 20150011
TI  - Cardiovascular consequences of sleep apnea: I -epidemiology.
AB  - Obstructive sleep apnea (OSA) is common in general population. There is an
      accumulating research evidence for an independent relationship between OSA and
      cardiovascular morbidity and mortality. This relationship is stronger in clinical
      cohorts compared with the general population, which suggests that concomitant OSA
      in subjects with traditionally recognized risk factors such as obesity,
      hypertension, smoking, and hyperlipidemia may provide an additive risk factor for
      the cardiovascular consequences. In the current article, the clinic-and
      population-based epidemiologic data will be reviewed in this context.

PMID- 20150012
TI  - [Echocardiographic longitudinal, radial, circumferential and rotational
      synchronization disturbance in predicting response to cardiac resynchronization
      therapy].
AB  - Several echocardiographic methods have been proposed to assist patient selection
      for cardiac resynchronization therapy. Color-coded tissue Doppler is one of the
      most promising methods to quantify mechanical dyssynchrony. However, tissue
      Doppler data are affected by Doppler angle of incidence and tethering or
      translational motion. Furthermore tissue Doppler based modalities are good for
      longitudinal motion analysis but limited in other directions of wall motion such
      as radial, circumferential, and rotational. Speckle tracking is a more recent
      technique that allows accurate calculation of regional radial and circumferential
      strain as well as regional rotation for dyssynchrony analysis. Although no ideal
      echocardiographic method exists that integrates regional dyssynchrony data in all
      contraction directions as yet, technical refinements and advances in
      understanding of pathophysiology will help to improve the study of mechanical
      dyssynchrony.

PMID- 20150013
TI  - [Association of Gerbode-type defect and Wolff-Parkinson-White syndrome with
      Ebstein's anomaly].

PMID- 20150014
TI  - Resistant radial artery spasm during coronary angiography via radial approach
      responded to local warm compress.

PMID- 20150015
TI  - Repair of a traumatic aorto-right ventricular fistula following a stab wound.

PMID- 20150016
TI  - Acute stress-induced late drug-eluting stent thrombosis leading to hyperacute
      myocardial infarction.

PMID- 20150017
TI  - Increased platelet serotonin levels in hypertensive patients already taking
      antihypertensive drugs.

PMID- 20150018
TI  - Harvesting internal mammarian artery by using ultrasound harmonic scalpel:
      experience of 154 cases.

PMID- 20150020
TI  - Histopathologic findings of autoimmunity in thyroid, pituitary, and adrenal
      diseases in chronic hepatitis C postmortem cases.
AB  - OBJECTIVE: To assess the histologic prevalence of immune-mediated thyroid,
      pituitary, and adrenal diseases in postmortem cases with hepatitis C. METHODS: We
      reviewed 108 consecutive cases of chronic hepatitis C in patients in whom a
      complete postmortem examination was performed. All microscopic and histologic
      slides of the thyroid, pituitary, and adrenal reports were reviewed and assessed
      for evidence of autoimmune diseases. These were compared with a control group of
      100 postmortem cases without hepatitis C. RESULTS: In chronic hepatitis C
      infection, there is a heightened immune response resulting in many autoimmune
      diseases. The commonest endocrinopathy in association with this chronic infection
      is thyroid disease, a finding confirmed in our current study. Among the 108
      postmortem cases of hepatitis C, there were 14 cases (13%) with evidence of
      thyroiditis. No cases of pituitary or adrenal disease were found. The mean age of
      the patients was 52 years (range, 29 to 68). This frequency compared with 7 cases
      of thyroid disease (7%) in the control group (no significant difference between
      the 2 groups). CONCLUSION: On the basis of our postmortem data, thyroid disease
      was the only major endocrinopathy associated with hepatitis C infection, with a
      prevalence of 13%. This was comparable with other serologic and nonhistologic
      antemortem findings. There was no evidence of pituitary or adrenal involvement.

PMID- 20150022
TI  - Visual vignette. Hypopituitarism and central diabetes insipidus due to an
      intracranial tumor (germinoma).

PMID- 20150021
TI  - Treatment of hypogonadism with testosterone in patients with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To investigate the effect of testosterone treatment on insulin
      resistance, glycemic control, and dyslipidemia in Asian Indian men with type 2
      diabetes mellitus (T2DM) and hypogonadism. METHODS: We conducted a double-blind,
      placebo-controlled, crossover study in 22 men, 25 to 50 years old, with T2DM and
      hypogonadism. Patients were treated with intramuscularly administered
      testosterone (200 mg every 15 days) or placebo for 3 months in random order,
      followed by a washout period of 1 month before the alternative treatment phase.
      The primary outcomes were changes in fasting insulin sensitivity (as measured by
      homeostasis model assessment [HOMA] in those patients not receiving insulin),
      fasting blood glucose, and hemoglobin A1c. The secondary outcomes were changes in
      fasting lipids, blood pressure, body mass index, waist circumference, waist-to
      hip ratio, and androgen deficiency symptoms. Statistical analysis was performed
      on the delta values, with the treatment effect of placebo compared with the
      effect of testosterone. RESULTS: Treatment with testosterone did not
      significantly influence insulin resistance measured by the HOMA index (mean
      treatment effect, 1.67 +/- 4.29; confidence interval, -6.91 to 10.25; P>.05).
      Mean change in hemoglobin A1c (%) (-1.75 +/- 5.35; -12.46 to 8.95) and fasting
      blood glucose (mg/dL) (20.20 +/- 67.87; -115.54 to 155.94) also did not reach
      statistical significance. Testosterone treatment did not affect fasting lipids,
      blood pressure, and anthropometric determinations significantly. CONCLUSION: In
      this study, testosterone treatment showed a neutral effect on insulin resistance
      and glycemic control and failed to improve dyslipidemia, control blood pressure,
      or reduce visceral fat significantly in Asian Indian men with T2DM and
      hypogonadism.

PMID- 20150023
TI  - Change in adrenal mass size as a predictor of a malignant tumor.
AB  - OBJECTIVE: To assess the value of adrenal mass absolute growth, growth rate, and
      percentage growth rate on serial imaging for distinguishing benign from malignant
      adrenal masses. METHODS: We retrospectively reviewed the Cleveland Clinic medical
      record data on 136 adrenalectomies or biopsies in 132 patients with 2 imaging
      studies performed more than 2 months apart (during 1997 to 2008). RESULTS: There
      were 111 benign (81.6%) and 25 malignant (18.4%) adrenal masses. With use of
      receiver operating characteristic curve analysis, all 3 aforementioned growth
      measures showed similar levels of discrimination for the entire study group as
      well as for the subgroups with 3 to 12 months of follow-up (n = 75 masses) and
      noncontrast computed tomography Hounsfield units >10 or not reported (n = 111
      masses). After adjustment for other factors, the 3 growth measures remained
      statistically significant predictors of a malignant tumor. The absolute growth
      cutoff value of 0.8 cm had the highest sum of sensitivity and specificity of 72%
      and 81.1%, respectively. We could not identify an adrenal mass growth cutoff
      value to provide 100% sensitivity or specificity to confirm or exclude the
      presence of a malignant lesion. In 3 patients with metastatic lesions, no growth
      or a decrease in mass size during a period of 4 to 36 months was observed.
      CONCLUSION: In this study, the largest with surgical histopathology findings as
      the "gold standard" for diagnosis, change in adrenal mass size was a significant
      predictor of a malignant tumor. Nevertheless, we could not identify an adrenal
      mass growth cutoff value for reliable confirmation or exclusion of a malignant
      lesion. Change in adrenal mass size should be used in conjunction with other
      imaging and clinical characteristics when surgical resection is being considered.

PMID- 20150024
TI  - Managing diabetes in the heat: potential issues and concerns.
AB  - OBJECTIVE: To review issues surrounding management of diabetes mellitus during
      times of extreme high temperatures. METHODS: Materials used for this article were
      identified through a search of MEDLINE publications from 1966 to 2009. We chose
      English-language articles by using terms that cross-referenced diabetes mellitus,
      hot temperature, heat, desert, and insulin. RESULTS: Persons with diabetes may
      have greater susceptibility to adverse effects from heat (ie, increased number of
      emergency department visits and hospitalizations, increased occurrence of
      dehydration and electrolyte abnormalities, and higher death rate) than persons
      without diabetes. Alterations in glucose homeostasis may occur, and changes in
      insulin kinetics and stability are possible. The impact of heat exposure on
      equipment performance (eg, glucometers) must be considered. CONCLUSIONS: Having
      diabetes places a person at risk for heat-related health problems. Physicians
      must be aware of possible complications that diabetic patients may encounter in
      summer heat to prevent problems. Patient educational materials should be
      developed relating to self management skills in the heat, and the topic should be
      included in standard diabetes education programs when applicable.

PMID- 20150025
TI  - Osteopetrosis and congenital hypothyroidism complicated by slipped capital
      femoral epiphysis.
AB  - OBJECTIVE: To describe a 13-year-old girl with unilateral slipped capital femoral
      epiphysis (SCFE), who presented with an acute onset limp during follow-up for
      congenital hypothyroidism and osteopetrosis. METHODS: We present a case report
      detailing the patient's history as well as clinical, laboratory, and imaging
      findings and discuss the related literature. RESULTS: The patient had been
      diagnosed elsewhere with congenital hypothyroidism, and levothyroxine therapy was
      initiated when she was 20 days of age; however, adherence to the treatment was
      irregular. Both her weight and her height were below the 5th percentile, her
      breast development and pubic hair were consistent with Tanner stage 1, and she
      had mental retardation and atypical facies. Her gait was antalgic; no muscle
      atrophy or shortness in the affected leg was present. On laboratory
      investigation, thyroid function tests were concordant with primary
      hypothyroidism. Her bone age was estimated as 8 years. Dual-energy x-ray
      absorptiometry revealed increased bone mineral density. Radiographic studies
      disclosed striking opacity of the bones of the pelvis and sclerosis at the skull
      base. Computed tomography of the affected left lower limb showed a fragmented
      appearance of the capital femoral epiphysis and thickening and irregularities of
      the physis line on the left, consistent with SCFE. CONCLUSION: We underscore the
      possible facilitator role of osteopetrosis in the pathogenesis of SCFE, suggest
      the need to consider SCFE in the differential diagnosis when a lower extremity
      abnormality is detected in patients with congenital hypothyroidism or delayed
      puberty (or both), and emphasize this association with osteopetrosis.

PMID- 20150026
TI  - Rapid-acting insulin analogues in Basal-bolus regimens in type 1 diabetes
      mellitus.
AB  - OBJECTIVE: To compare rapid-acting insulin analogues with regular human insulin
      in terms of hemoglobin A1c, hypoglycemia, and insulin dose when used in a basal
      bolus regimen in patients with type 1 diabetes mellitus. METHODS: MEDLINE and
      congress proceedings were searched for randomized controlled trials comparing
      prandial insulins in a basal-bolus regimen in adults or children/adolescents with
      type 1 diabetes. Studies in pregnancy, observational studies, studies that
      compared premixed insulin or continuous subcutaneous insulin infusion/insulin
      pumps, and studies where the basal insulin was also changed were excluded. Only
      studies reporting baseline-endpoint change in insulin dose, or baseline and/or
      endpoint values, were included. RESULTS: Twenty-eight studies were identified
      (insulin glulisine, 4; insulin aspart, 7; insulin lispro, 17). Twenty-five
      studies compared a rapid-acting insulin analogue with regular human insulin, and
      3 trials compared 2 rapid-acting insulin analogues. Overall, rapid-acting insulin
      analogues in a basal-bolus regimen provided similar or greater improvements in
      glycemic control than regular human insulin at similar insulin doses, as well as
      a lower incidence of hypoglycemia. CONCLUSIONS: Results of the studies identified
      in this literature review indicate that a basal-bolus regimen with prandial rapid
      acting insulin analogue provides advantages over basal-bolus regimens using
      prandial regular human insulin, providing improvements in glycemic control
      comparable to those obtained with regular human insulin, as well as a lower
      incidence of hypoglycemia.

PMID- 20150027
TI  - Hypovitaminosis D and bone mineral density in human immunodeficiency virus
      infected men from India, with or without antiretroviral therapy.
AB  - OBJECTIVE: To study the vitamin D status and bone mineral density (BMD) in men
      infected with human immunodeficiency virus (HIV) in a tertiary care center from
      southern India. METHODS: We conducted a cross-sectional study of 35 HIV-infected
      men (between 20 and 50 years old) receiving highly active antiretroviral therapy
      (HAART) (group 1) in comparison with 35 age- and body mass index-matched HIV
      positive antiretroviral therapy-naive men (group 2) and 35 HIV-negative healthy
      control subjects (group 3). RESULTS: A significantly greater proportion (P =
      .002) of patients (74%) in the HAART group had vitamin D deficiency (<20 ng/mL)
      in comparison with the other 2 groups (37% in each group). The mean intact
      parathyroid hormone level was higher (P<.001) and the mean duration of exposure
      to sunlight was lower (P = .001) in the HAART group than in the other 2 groups.
      By logistic regression analysis, HAART was found to be significantly associated
      with vitamin D deficiency. The BMD in the femoral neck was significantly lower in
      men with HIV infection who were receiving HAART in comparison with the other 2
      groups (P = .006). On multivariate logistic regression, older age, low body mass
      index, and high parathyroid hormone levels emerged as factors significantly
      associated with decreased BMD at the femoral neck. CONCLUSION: A significant
      proportion of patients receiving HAART had vitamin D deficiency. The secondary
      hyperparathyroidism probably due to vitamin D deficiency is an important
      contributing factor for the observed changes in BMD. Vitamin D deficiency noted
      in this group is probably multifactorial, and further research is needed to
      determine whether the effect of HAART on vitamin D metabolism is an additional
      causative factor and what benefit vitamin D supplementation might confer in these
      patients.

PMID- 20150028
TI  - Vitamin D role and use in prediabetes.
AB  - OBJECTIVE: To review the role of vitamin D in prediabetes on the basis of
      evidence from human studies. METHODS: English-language literature in MEDLINE
      (January 1969-July 2009) was searched for observational studies and randomized
      controlled trials of vitamin D deficiency and treatment in prediabetes, including
      impaired fasting glucose, impaired glucose tolerance, and metabolic syndrome.
      Search terms included hyperglycemia, glucose, glycohemoglobin, insulin
      resistance, diabetes, homeostasis model assessment, insulin secretion, vitamin D,
      and related terms. Publications were also identified from review articles and
      references in the found articles. Abstracts, conference proceedings, case
      reports, and letters were excluded. Articles concerning only type 1 and type 2
      diabetes, hemodialysis, or hyperparathyroidism and studies in children were also
      excluded. RESULTS: Vitamin D insufficiency is defined by a circulating 25
      hydroxyvitamin D concentration less than 30 ng/mL, and it is prevalent in the
      United States (77% of the population). Most cross-sectional and prospective
      studies in various populations show inverse association between circulating 25
      hydroxyvitamin D and fasting plasma glucose, impaired glucose tolerance,
      hemoglobin A1c, metabolic syndrome, and incidence of prediabetes. A few clinical
      trials suggest beneficial effect of vitamin D supplementation in prediabetes,
      including improved insulin secretion, basal fasting insulin sensitivity, and
      postprandial peripheral insulin resistance. The limitations of the studies are
      small sample size, short duration of follow-up, lack of control groups, and
      inability to achieve vitamin D sufficiency with treatment. CONCLUSION: Available
      data suggest that achieving vitamin D sufficiency may be beneficial in patients
      with prediabetes, although clinical trials are needed to provide evidence-based
      recommendations.

PMID- 20150029
TI  - Effect of the juice of lime (Citrus aurantifolia) on estrous cycle and ovulation
      of Sprague-Dawley rats.
AB  - OBJECTIVE: To determine the effect of lime juice on the estrous cycle and
      ovulation of cyclic female rats. METHODS: Twenty-five adult female Sprague-Dawley
      rats were used. The study was divided into 2 experiments (I and II). In
      experiment I, 15 rats were randomly subclassified into 3 groups (Ia, Ib, and Ic)
      of 5 rats each. The estrous cycles of the rats were studied for the first 16 days
      to establish cyclicity, after which lime juice was administered by gastric gavage
      for the next 24 days. Rats in group Ia received 1 mL of undiluted lime juice,
      rats in group Ib received 1 mL of 50% diluted lime juice, and rats in group Ic
      (control animals) received only distilled water. In experiment II, 10 female rats
      were used and were categorized into 2 groups (IIa and IIb), with 5 rats in each
      group. Rats in group IIa received 1 mL of undiluted lime juice during the morning
      of proestrus, and those in group IIb received only distilled water on the day of
      proestrus. The rats were killed the next day with use of chloroform anesthesia.
      The upper parts of the oviducts were excised and examined under the light
      microscope for assessment of the number of ova shed. RESULTS: There was an
      irregular pattern in all phases of the estrous cycle of 100% of the rats given
      undiluted lime juice and in 80% of those given 50% diluted lime juice. There was
      a significant (P = .001) reduction in the number of ova shed in rats administered
      undiluted lime juice in comparison with the control animals. Ovulation was
      partially blocked, as shown by the reduced number of ova observed in the oviducts
      from the rats given undiluted lime juice (5.10 +/- 2.37) in comparison with the
      control rats (12.70 +/- 1.14). CONCLUSION: In rats, lime juice causes
      irregularity of the estrous cycle, partially blocks ovulation, and may possibly
      compromise fertility.

PMID- 20150030
TI  - Antiovulatory and anti-implantation potential of the methanolic extract of seeds
      of Abrus precatorius in the rat.
AB  - OBJECTIVE: To investigate the effect of the methanolic extract of seeds of Abrus
      precatorius on the estrous cycle, ovulation, and implantation of fetuses in
      Sprague-Dawley rats. METHODS: Cyclic female rats were randomly classified into 4
      groups (A through D). Treated rats in group A had daily vaginal smears for a
      total of 64 consecutive days while being fed A precatorius extract for the first
      32 of those days. Treated rats in group B received a single oral dose of the
      extract on the day of proestrus and were killed the following morning so that
      shed ova could be counted. Treated rats in group C received A precatorius extract
      from postcoital day 1 to 10 and were killed on day 12 to assess for anti
      implantation effect, whereas the treated dams in group D received the extract
      from the 6th to the 19th day of gestation. The control animals in all 4 groups
      received an equal volume of distilled water. RESULTS: The methanolic extract of A
      precatorius caused a reversible disruption in the estrous cycle of the regularly
      cyclic rats and completely blocked ovulation in all the treated rats. Despite
      successful mating of the female rats with male rats of proven fertility, uterine
      dissection on postcoital day 12 revealed neither implantation nor resorption
      sites in all the animals treated with A precatorius. The extract of A precatorius
      caused a decrease in mean body weight, mean crown-rump length, and mean tail
      length of fetuses of the treated rats. CONCLUSION: There is a need to continue
      the search for new antifertility agents that have minimal side effects and
      widespread acceptability in addition to being reversible, affordable, and
      accessible. In this study, methanolic extract of A precatorius seeds caused
      reversible alterations in the estrous cycle pattern and completely blocked
      ovulation in Sprague-Dawley rats. In addition, the extract demonstrated anti
      implantation activity and the potential to affect gross fetal morphometry in
      rats.

PMID- 20150031
TI  - Repair of extensive thoracoabdominal aortic aneurysm with a tetrafurcate graft:
      midterm results of 63 cases.
AB  - OBJECTIVE: The objective is to present a method for maintaining the spinal cord
      blood supply and our midterm results for using a tetrafurcate graft in extensive
      thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: From August 2003 to
      October 2007, we used a tetrafurcate graft to perform repairs to TAAAs of
      Crawford extent II in 63 consecutive patients. The mean age of this group of
      patients was 39.98 +/- 10.62 years, and 46 (73%) of them were male. All of the
      procedures were performed under profound hypothermia with a short interval of
      circulatory arrest. T6 to T12 intercostal arteries were reconstructed as a "neo
      intercostal artery" (N-IA) and were connected to an 8-mm sidearm of the graft to
      maintain the spinal cord blood supply. Visceral arteries were joined into a patch
      and were anastomosed to the end of the main graft. The left renal artery was
      anastomosed to an 8-mm sidearm or joined to the patch. The other 10-mm sidearms
      were anastomosed to iliac arteries. RESULTS: With 100% follow-up, the early
      mortality rate was 7.94%. The incidence of cerebral complications was 9.52%.
      Temporary paraplegia was observed in 2 patients, and paraparesis occurred in 1
      patient. Pulmonary complication was the most common morbidity in this group
      (25.40%). Two patients with Marfan syndrome had N-IA artery pseudoaneurysms
      during follow-up. The mean survival time of this group was 50.64 +/- 2.13 months,
      with survival rates of 92.06% after 1 year, 88.38% after 2 years, and 86.11%
      after 3 years. CONCLUSION: The N-IA may play an important role in spinal cord
      protection, and N-IA pseudoaneurysm should be avoided in Marfan syndrome
      patients. The use of a tetrafurcate graft is a reliable method for TAAA repair,
      with satisfactory midterm results.

PMID- 20150032
TI  - Overestimation of the operative risk by the EuroSCORE also in high-risk patients
      undergoing aortic valve replacement with a stentless biological prosthesis.
AB  - BACKGROUND: The EuroSCORE generally overestimates the risk of standard aortic
      valve replacement (AVR). The predictive value of this risk algorithm for high
      risk patients undergoing stentless AVR is unclear; therefore, we compared the
      EuroSCORE prediction with our results in this patient population. METHODS: One
      hundred thirty-two patients with a logistic EuroSCORE of at least 10 (mean, 25)
      underwent primary isolated AVR with a stentless bioprosthesis between January
      2004 and December 2007. Seventy-one patients (54%) were octogenarians or
      nonagenarians, 62 (47%) had a reduced left ventricular ejection fraction, and 46
      (35%) had an extracardiac arteriopathy. RESULTS: Maximum/mean pressure gradients
      for the implanted valve prostheses were 19/11 mm Hg, and the mean regurgitation
      grade was 0.06. Stroke occurred in 3% of the patients, and a permanent pacemaker
      was required in 3%. The 30-day mortality rate was 8%. Another 5% of the patients
      died after the 30th postoperative day but within the same hospital admission. The
      predicted mortality was almost 100% greater than the observed mortality.
      CONCLUSION: We observed a mortality rate that was 50% lower than that predicted
      by the logistic EuroSCORE. Therefore, one should not hesitate to use stentless
      valves in high-risk patients because the EuroSCORE greatly overestimates their
      surgical risk.

PMID- 20150033
TI  - Premolded bovine pericardial chords for replacement of ruptured or elongated
      chordae tendineae.
AB  - BACKGROUND: The aim of this study was to assess by Doppler echocardiography (ECO)
      the functioning of the mitral valve apparatus in patients who have undergone
      implantation of standardized bovine pericardium chordae (SBPC) for replacement of
      ruptured or elongated chordae tendineae with significant thinning. METHODS: SBPC
      were implanted in 31 patients who had mitral insufficiency due to rupture of
      chordae tendinae or elongated chordae with significant thinning. Patient ages
      ranged from 19 to 85 years (mean of 58 years). The most frequent cause of mitral
      insufficiency was fibroelastic degeneration in 25 patients (80.6%). The SBPC were
      fashioned as a set, joined at their extremities by 2 polyester-reinforced rods
      forming a monobloc. The SBPC were 2-mm wide and were positioned parallel to one
      another at a distance of 3 mm. Each set of SBPC had a corresponding measurer, and
      their length ranged from 20 to 35 mm. In 21 patients (67.7%) the SBPC were
      implanted in the posterior leaflet and in 10 patients (32.3%) in the anterior
      leaflet (in 2 patients concurrently in the anterior and posterior leaflets). All
      patients were assessed by ECO postoperatively, with a 20-month mean follow-up
      time (range 6-45 months). RESULTS: One patient (3.2%) died of pulmonary embolism
      during the early postoperative period. Postoperative ECO showed absence of mitral
      regurgitation in 17 patients (54.8%), mild regurgitation in 9 (29.0%), and mild
      to-moderate regurgitation in 4 (12.9%). Opening and mobility of the mitral valve
      were normal in the 30 surviving patients. CONCLUSION: The ECO revealed good
      functionality of the mitral valve apparatus with appropriate leaflet coaptation
      in patients who had undergone implantation of SBPC for replacement of ruptured or
      elongated and thinned chordae. A longer follow-up is required to assess absence
      of calcification and/or degeneration of the SBPC.

PMID- 20150034
TI  - Case report: nonarrhythmogenic right ventricular dysplasia presenting with severe
      right ventricular failure in an adolescent.
AB  - Right ventricular dysplasia is usually discovered by the presence of ventricular
      arrhythmia. As arrhythmia is an epiphenomenon, the first presentation of some
      cases can be primarily heart failure. We describe an adolescent girl who
      presented with progressive right heart failure and whose hallmark was fibrofatty
      replacement of ventricular muscle, especially of the right side, without
      ventricular arrhythmia. The patient was successfully treated by orthotopic heart
      transplantation.

PMID- 20150035
TI  - Intra-atrial placement of a mitral prosthesis in a patient with severe mitral
      annulus calcification: a case report.
AB  - An 88-year-old woman presented with increasing dyspnea and angina. She was found
      to have severe aortic stenosis, 2-vessel coronary artery disease, and severe
      mitral regurgitation. During surgery the patient was noted to have such severe
      mitral annular calcification that performing a conventional mitral valve
      replacement would have significantly increased the operative risk. Instead, an 8
      mm Dacron graft was sutured onto the sewing cuff of a reversed 23-mm Mosaic
      porcine aortic valve (Medtronic, Minneapolis, MN, USA). The Dacron graft was then
      sutured to the left atrial wall surrounding the calcified mitral annulus. A
      bioprosthetic aortic valve replacement, along with a 2-vessel coronary artery
      bypass procedure, was also performed.

PMID- 20150036
TI  - A rare reason for pulmonary hypertension: primary sarcoma of the pulmonary
      artery.
AB  - Primary sarcoma of the pulmonary artery (PSPA) is an extremely rare tumor of the
      cardiovascular system. The prognosis is very poor. The clinical symptoms and
      imaging findings imitate those of pulmonary emboli, causing delays in diagnosis.
      In this case report, we describe a 73-year-old man with PSPA who initially was
      admitted with exertional shortness of breath. Transthoracic echocardiographic
      evaluation revealed 2 masses in the pulmonary artery causing pulmonary
      hypertension. The patient underwent operation, but he could not be weaned off
      cardiopulmonary bypass at the end of the operation and died. Pathologic
      examination of the masses revealed pulmonary sarcoma. Although this patient was
      admitted to our clinic only 2 weeks after the initial symptoms, he already had
      distal metastases.

PMID- 20150037
TI  - Direct myocardial implantation of human fetal stem cells in heart failure
      patients: long-term results.
AB  - BACKGROUND: End-stage heart failure (HF) is refractory to current standard
      medical therapy, and the number of donor hearts is insufficient to meet the
      demand for transplantation. Recent studies suggest autologous stem cell therapy
      may regenerate cardiomyocytes, stimulate neovascularization, and improve cardiac
      function and clinical status. Although human fetal-derived stem cells (HFDSCs)
      have been studied for the treatment of a variety of conditions, no clinical
      studies have been reported to date on their use in treating HF. We sought to
      determine the efficacy and safety of HFDSC treatment in HF patients. METHODS AND
      RESULTS: Direct myocardial transplantation of HFDSCs by open-chest surgical
      procedure was performed in 10 patients with HF due to nonischemic, nonchagasic
      dilated cardiomyopathy. Before and after the procedure, and with no changes in
      their preoperative doses of medications (digoxin, furosemide, spironolactone,
      angiotensin-converting enzyme inhibitors, angiotensin receptor blockers,
      betablockers), patients were assessed for New York Heart Association (NYHA)
      class, performance in the exercise tolerance test (ETT), ejection fraction (EF),
      left ventricular end-diastolic dimension (LVEDD) via transthoracic
      echocardiography, performance in the 6-minute walk test, and performance in the
      Minnesota congestive HF test. All 10 patients survived the operation. One patient
      had a stroke 3 days after the procedure, and although she later recovered, she
      was unable to perform the follow-up tests. Another male patient experienced
      pericardial effusion 3 weeks after the procedure. Although it resolved
      spontaneously, the patient abandoned his control tests and died 5 months after
      the procedure. An autopsy of the myocardium suggested that new young cells were
      present in the cardiomyocyte mix. At 40 months, the mean (+/-SD) NYHA class
      decreased from 3.4 +/- 0.5 to 1.33 +/- 0.5 (P = .001); the mean EF increased 31%,
      from 26.6% +/- 4% to 34.8% +/- 7.2% (P = .005); and the mean ETT increased
      291.3%, from 4.25 minutes to 16.63 minutes (128.9% increase in metabolic
      equivalents, from 2.46 to 5.63) (P < .0001); the mean LVEDD decreased 15%, from
      6.85 +/- 0.6 cm to 5.80 +/- 0.58 cm (P < .001); mean performance in the 6-minute
      walk test increased by 43.2%, from 251 +/- 113.1 seconds to 360 +/- 0 seconds (P
      = .01); the mean distance increased 64.4%, from 284.4 +/- 144.9 m to 468.2 +/-
      89.8 m (P = .004); and the mean result in the Minnesota test decreased from 71 +/
      27.3 to 6 +/- 5.9 (P < .001). CONCLUSION: Although these initial findings
      suggest direct myocardial implantation of HFDSCs is feasible and improves cardiac
      function in HF patients at 40 months, more clinical research is required to
      confirm these observations.

PMID- 20150038
TI  - Xiphoid lower-sternotomy approach for multivessel revascularization of the left
      internal mammary artery to the left anterior descending artery and right internal
      mammary artery inflow to the other vessels.
AB  - BACKGROUND: We describe the technical details and the preliminary results of a
      new surgical approach for multivessel disease that involves using a lower T
      sternotomy, grafting of the left internal mammary artery (LIMA) to the left
      anterior descending coronary artery (LAD) and use of the right internal mammary
      artery (RIMA) as inflow to the other vessels. OPERATIVE TECHNIQUE: The sternotomy
      was made from the xiphoid up to the fourth intercostal space and then was
      continued transversally (T incision). The LIMA was harvested for a length of
      approximately 8 cm, with preservation of the distal part. The vein was
      simultaneously taken from the leg. The RIMA was dissected for a length of
      approximately 5 cm, and the distal part was occluded. Then, 3 mg/kg heparin was
      given. The anastomosis between the vein and the RIMA was performed. The distal
      venous anastomoses were done either singly or sequentially. The anterior or
      posterior route was chosen according to the patient's anatomy. The LIMA was then
      anastomosed to the LAD. One drain was placed. The sternum was closed with 4
      wires, 2 for the T incision and 2 for the sternum. RESULTS: Between September and
      December 2008, 9 patients underwent their operations with this technique. The
      mean age was 60 years (range, 55-68 years). The mean number of grafts was 2.8.
      The mean hospital stay was 5.2 days. Operative mortality was 0%. All patients
      were reevaluated with 16-slice multislice computed tomography, and all grafts
      were patent. At the 3-month follow-up, all patients were alive and free of
      symptoms. CONCLUSION: This minimally invasive technique is a useful alternative
      for complete revascularization. The sternal mammary supply and the upper part of
      the sternum are preserved.

PMID- 20150039
TI  - Quality of Life after 114 months of follow-up following geometric reconstruction
      of the left ventricle by endoventriculoplasty with septal exclusion.
AB  - BACKGROUND: The purpose of this study was to present the surgical experience of
      the Institute of Cardiovascular Surgery of West of Parana (ICCOP) with respect to
      the treatment of left ventricle aneurysms by endoventriculoplasty with septal
      exclusion (EVSE) and to evaluate the quality of life of these patients after a
      114-month follow-up. METHODS: Between April 1999 and April 2006, 28 patients
      underwent EVSE. Preoperative, transoperative, and late postoperative clinical and
      echocardiographic variables were analyzed retrospectively. In addition,
      latepostoperative quality of life was evaluated with questionnaire SF-36
      (Brazilian version). The mean age (+/-SD) of the group was 59.0 +/- 9.5 years,
      and 23 of the patients were male. Seventeen patients were in New York Heart
      Association functional class IV, and the mean preoperative EuroSCORE was 8.2 +/-
      2.3. The mean preoperative values for the ejection fraction (EF) and the end
      systolic and end-diastolic left ventricular volumes were 32.3% +/- 9.2%, 113.9 +/
      36.0 mL, and 179.2 +/- 48.4 mL, respectively. RESULTS: The in-hospital mortality
      rate was 14.3%, with the major causes of morbidity being low cardiac output
      syndrome and arrhythmias. The mean follow-up period was 5.9 +/- 3.4 years. The
      left ventricular EF and the aortic cross-clamping time were the significant
      factors for hospital and late mortality (P = .0222, and P = .0123, respectively).
      The actuarial survival curve showed survival rates of 82.1 +/- 7.2%, and 54.7 +/-
      22.9%, before and after 107 months of follow-up. The overall score for the
      quality of life showed an improvement. CONCLUSION: EVSE surgery is an effective
      option for treating this group of patients, with improvement noted in left
      ventricular function and in the patients' quality of life, despite the high in
      hospital mortality.

PMID- 20150040
TI  - Coronary morphology and conduction system disturbance induced by therapeutic
      embolization of the coronary septal artery.
AB  - BACKGROUND: Percutaneous transluminal septal myocardial alcohol ablation (PTSMAA)
      is not a procedure without complications. It may produce heart arrhythmias,
      especially those due to disturbances of atrioventricular (AV) and
      interventricular (IV) electrical conduction. OBJECTIVE: The goal of this study
      was to evaluate the relationship between the anatomical patterns of the right
      coronary artery and the left anterior descending artery (LAD) and to relate them
      to the AV and IV bundle branch blocks provoked by PTSMAA. METHOD: Twenty patients
      with obstructive hypertrophic cardiomyopathy resistant to treatment with drugs
      successfully underwent PTSMAA. Electrocardiographic analyses were done before and
      after PTSMAA, and the results were compared with the abnormal septal anatomy.
      RESULTS: The effectiveness of PTSMAA was obtained in 18 (90%) of the 20 patients
      by ethanolization of the first great septal branch. In the other 2 patients
      (10%), 2 septal branches underwent alcoholization. First-grade temporary AV block
      (AVB) was observed in 6 patients (30%). Ten patients experienced severe
      bradycardia due to total AVB that required a temporary pacemaker, but 3 of the
      patients (15%) required a permanent pacemaker. Fourteen patients (70%)
      experienced permanent complete right branch block, and 2 developed incomplete
      left anterior block and incomplete left posterior block. Six patients presented
      with no electrical conduction disturbance at all. CONCLUSION: According to the
      results of the present investigation with the AV node artery derived from the
      right coronary artery in all cases, complete and permanent AV conduction system
      blockade occurred after PTSMAA in all types of anatomy regarding the observed
      LAD.

PMID- 20150041
TI  - Dipyridamole and low doses of heparin as a new successful physiopathologic and
      therapeutic approach in 2 cases of disseminated intravascular coagulation.
AB  - OPERATIVE: We report 2 cases of disseminated intravascular coagulation (DIC)
      successfully treated with the combination of the platelet adhesiveness blocker
      dipyridamole and low doses of intravenous heparin. METHODS: The first patient was
      a 17-year-old boy with septic arthritis; the second patient was a 12-year-old boy
      with a liver abscess. Both had hemocultures positive for Staphylococcus aureus.
      The diagnosis of DIC was defined by clinical signs of septicemia with fever,
      tachypnea, peripheral vasoconstriction, and low platelet counts (67,000/mm3 and
      47,000/mm3, respectively). The second patient also presented with acute ischemia
      of the fingers and toes. General care was provided in the intensive care unit,
      and high doses of antibiotics were provided continuously (metronidazole and
      oxacillin or ceftriaxone). A 5% glucose solution containing dipyridamole
      (Persantine; Istituto De Angeli/Boheringer Ingelheim, Reggello, Italy) was
      administered by continuous intravenous infusion (20 mg/24 hours). In addition,
      regular heparin (Liquemin; Roche, Indianapolis, IN, USA) was administered at a
      dosage of 250 microg/kg per hour or 25 IU/kg per hour (6 mg/kg per 24 hours).
      These heparin doses are not able to promote complete blood anticoagulation.
      Treatment with heparin and dipyridamole was maintained for 10 days in the first
      patient and for 18 days in the second. RESULTS: By 48 hours after treatment with
      dipyridamole and low-dose heparin, both patients recovered and presented with a
      good clinical condition and increased numbers of circulating platelets. Both
      patients were discharged in a safe clinical condition in the second month after
      hospital admission. CONCLUSION: Successful clinical recovery of 2 young patients
      with DIC with an unfavorable clinical evolution and a prognosis for a lethal
      outcome was achieved with the combination of a continuous infusion of
      dipyridamole and low doses of heparin.

PMID- 20150042
TI  - Cardiac effects of postconditioning depend critically on the duration of
      reperfusion and reocclusion episodes.
AB  - OBJECTIVE: The objective of the present study was to evaluate the effects of
      ischemic postconditioning on left ventricular function in isolated rat hearts.
      METHODS: The hearts of 24 Wistar rats were were isolated, perfused immediately,
      and distributed into 3 groups: GI, control (n = 8); GII, three 10-second cycles
      of postconditioning (n = 8); and GIII, three 30-second cycles of postconditioning
      (n = 8). After a 15-minute stabilization period, all hearts underwent 20 minutes
      of global ischemia following 20 minutes of reperfusion. At times t0 (control),
      t5, t10, t15, and t20 (0, 5, 10, 15, and 20 minutes of reperfusion,
      respectively), we recorded the heart rate, coronary flow, systolic pressure,
      +(dP/dt)max (maximum speed of increase in the left ventricular pressure), and 
      (dP/dt)max (maximum speed of decrease in the left ventricular pressure). Data
      were analyzed by a 1-way analysis of variance, followed by the Tukey test; a P
      value <.05 was considered statistically significant. RESULTS: There were no
      significant differences among the analyzed groups with respect to heart rate,
      coronary flow, systolic pressure, and -(dP/dt)max (P > .05); however,
      statistically significant differences in +(dP/dt)max between GII and GI and
      between GII and GIII occurred at t20 (GI, 1409.0 +/- 415.1 mm Hg/s; GII, 1917.3
      +/- 403.0 mm Hg/s; GIII, 1344.8 +/- 355.8 mm Hg/s) (GII versus GI, P = .04; GII
      versus GIII, P = .02). CONCLUSION: Ischemic postconditioning with three 10-second
      cycles of reperfusion/reocclusion was demonstrated effective for preserving
      +(dP/dt)max in isolated rat hearts that underwent 20 minutes of ischemia
      following 20 minutes of reperfusion.

PMID- 20150043
TI  - Effects of clonidine and isoflurane on the myocardial contractility behavior of
      isolated rat hearts.
AB  - Isoflurane is chosen as an anesthesia drug for cardiac surgeries, and its
      effectiveness and safety have been proved in countless clinical studies.
      Clonidine, a central alpha-agonist, has recently been added to isoflurane to
      attenuate sympathetic hyperactivity by acting directly on its site of origin in
      the central nervous system. The ability of alpha2-adrenoceptor agonists to
      inhibit central sympathetic outflow may benefit patients at risk of myocardial
      damage by improving myocardial oxygen demand and the supply ratio and
      contributing to hemodynamic stability. We investigated the effects of clonidine
      and isoflurane, alone and in combination, on the myocardial contractility of
      isolated rat hearts and found that use of clonidine plus isoflurane decreased the
      systolic pressure somewhat, but use of the drugs separately did not exhibit this
      effect. Clonidine plus isoflurane did not affect +(dP/dt)max, but it did decrease
      -(dP/dt)max significantly compared with the use of isoflurane alone. These
      results indicate that clonidine and isoflurane have the capacity to interact with
      each other. The capacity of clonidine to decrease isoflurane's inotropic effect
      could theoretically contribute to improving the myocardial oxygen demand and the
      supply ratio, decreasing surgical stress, and benefiting patients at risk of
      myocardial damage.

PMID- 20150044
TI  - First Turkish experiences of assisted beating-heart coronary artery bypass graft
      with the Impella Microaxial Ventricular Assist Device.
AB  - The importance of minimally invasive cardiac operations, performed off-pump,
      without the support of cardiopulmonary bypass (CPB), is continuously increasing.
      Complete revascularization of obstructed coronary arteries is needed to obtain a
      better long-term outcome. Insertion into the left ventricle of an efficient
      microaxial pump can be useful when targeting an important coronary artery located
      at posterior wall of the heart in a patient with hemodynamic deficiency. The use
      of such a device can enable surgeons to avoid conversion from a preplanned off
      pump strategy to traditional on-pump coronary bypass surgery. The Impella
      Microaxial Ventricular Assist Device (VAD) (Abiomed, Aachen, Germany) is a
      miniature pump with a 7-mm catheter and a flow rate of approximately 2.5-5 L/min.
      This device can enable cardiovascular surgery to be performed without damaging
      the left ventricle and causing serious aortic deficiency. Therefore, in patients
      with serious comorbidity, complete revascularization may be performed off pump,
      with the heart beating, because of the hemodynamic stability provided with the
      support of the microaxial intracardiac pump. If required, this pump can also
      support the heart during the early postoperative period. We report the first
      assisted beating-heart coronary artery bypass graft surgery performed with the
      Impella Microaxial VAD in our country. The surgery was performed on 2 patients
      considered high risk on the basis of EUROSCORE testing.

PMID- 20150045
TI  - Off-pump coronary artery bypass in a patient with congenital absence of the left
      pericardium and an extremely left-rotated heart.
AB  - Congenital anomalies of the pericardium are extremely rare and often difficult to
      diagnose. We describe a 66-year-old woman presenting with multivessel coronary
      artery disease and right heart insufficiency complicated by an extremely left
      rotated heart due to a congenital absence of left pericardium. A multidetector
      row computerized tomographic study was performed to evaluate the torsion of the
      heart as well as the physical relationship between the left internal thoracic
      artery and the left coronary system. Off-pump coronary surgery was scheduled.
      Both the operative and postoperative courses were uneventful and the patient was
      discharged after 11 days.

PMID- 20150046
TI  - Lower perfusion pressure during hypothermic cardiopulmonary bypass is associated
      with decreased cerebral blood flow and impaired memory performance 6 months
      postoperatively.
AB  - OBJECTIVES: We undertook to determine the influence of perfusion pressure during
      hypothermic cardiopulmonary bypass (CPB) on cerebral blood flow (CBF) and
      cognitive memory outcome at 6 months postoperatively. METHODS: Nineteen patients
      who underwent hypothermic nonpulsatile CPB for elective coronary artery bypass
      (CAB) surgery were evaluated by (133)Xe measurement of the CBF and by the
      Incidental Memory Assessment for evaluating cognitive memory (IMTscore), both at
      baseline before the operation (T(1)) and again at 5 to 6 months postoperatively
      (T(2)). RESULTS: Overall, the mean CBF fell significantly from 39 +/- 5 mL.(100
      g)(-1).min(-1) at T(1) to 33 +/- 3 mL.(100 g)(-1).min(-1) at T(2) (P < .001). The
      decrease in CBF from T(1) to T(2) (DeltaCBF(2-1)) correlated with a significant
      reduction in the IMTscore from T1 to T2 (DeltaIMTscore(2-1)) (P < .001) and with
      a mean arterial pressure during CPB (MAPCPB) of <60 mm Hg (P = .05). Cluster
      analysis of DeltaCBF(2-1) and DeltaIMTscore(2-1) demonstrated that the patients
      with the greatest decrease in CBF showed the greatest decrease in IMTscore,
      whereas cluster analysis of DeltaCBF(2-1) and MAPCPB indicated that patients with
      a perfusion pressure maintained at a mean of <60 mm Hg during CPB were prone to a
      greater decrease in later postoperative CBF. CONCLUSION: This study demonstrated
      that a MAPCPB of <60 mm Hg during CPB was associated with a significant decrease
      in CBF 6 months after CAB surgery and with an associated decrease in memory
      performance.

PMID- 20150047
TI  - The Hawaiian bobtail squid (Euprymna scolopes): a model to study the molecular
      basis of eukaryote-prokaryote mutualism and the development and evolution of
      morphological novelties in cephalopods.
AB  - The Hawaiian bobtail squid, Euprymna scolopes, is a cephalopod whose small size,
      short lifespan, rapid growth, and year-round availability make it suitable as a
      model organism. E. scolopes is studied in three principal contexts: (1) as a
      model of cephalopod development; (2) as a model of animal-bacterial symbioses;
      and (3) as a system for studying adaptations of tissues that interact with light.
      E. scolopes embryos can be obtained continually and can be reared in the
      laboratory over an entire generation. The embryos and protective chorions are
      optically clear, facilitating in situ developmental observations, and can be
      manipulated experimentally. Many molecular protocols have been developed for
      studying E. scolopes development. This species is best known, however, for its
      symbiosis with the luminous marine bacterium Vibrio fischeri and has been used to
      study determinants of symbiont specificity, the influence of symbiosis on
      development of the squid light organ, and the mechanisms by which a stable
      association is achieved. Both partners can be grown independently under
      laboratory conditions, a feature that offers the unusual opportunity to
      manipulate the symbiosis experimentally. Molecular and genetic tools have been
      developed for V. fischeri, and a large expressed sequence tag (EST) database is
      available for the host symbiotic tissues. Additionally, comparisons between light
      organ form and function to those of the eye can be made. Both types of tissue
      interact with light, but have divergent embryonic development. As such, they
      offer an opportunity to study the molecular basis for the evolution of
      morphological novelties.

PMID- 20150048
TI  - True yams (Dioscorea): a biological and evolutionary link between eudicots and
      grasses.
AB  - Dioscorea (true yams) is a large genus that contains species important as food
      (with edible tubers) or as sources of bioactive substances used in a range of
      applications. Dioscorea is a major staple food in many parts of the world,
      especially in West Africa and the Pacific islands, and serves as a famine food in
      many regions. It is a critically important but neglected crop, which is likely to
      increase in importance as climate change leads to necessary changes in global
      food systems. It is a herbaceous, climbing, tropical monocot that looks rather
      like a dicot, and is part of a lineage that is relatively closely related to the
      phylogenetically derived group containing the grasses. Therefore, it represents
      an important biological link between the eudicots and grasses--groups that
      contain all the model flowering plant species--and has the potential to fill gaps
      in our knowledge of plant biology and evolution. Yams also offer us the
      possibility to gain new insights into processes such as tuberization and sex
      determination, which cannot be studied in current model organisms. This
      combination of rising importance due to its socioeconomic significance and
      interesting biology and evolutionary position justify its potential as a model
      organism. This potential remains to be harnessed, and much of the current work on
      yam is directed toward its role as a food crop. This aspect will remain
      important, but its potential for answering questions of basic biological interest
      will be a major motivation for researchers interested in this organism.

PMID- 20150049
TI  - The embryonic development of the Hawaiian bobtail squid (Euprymna scolopes).
AB  - A staging series based on easily distinguishable morphological features is a
      basic and necessary tool for developmental studies. It provides a consistent
      reference for comparisons between independent studies, negates the need to know
      when fertilization occurred, allows correlation of the phase of development with
      the time of development (to facilitate collection of embryos at specific stages),
      and allows comparisons between species. Given the growing interest in Hawaiian
      bobtail squid (Euprymna scolopes) as a contemporary cephalopod developmental
      system, this article provides a detailed survey of E. scolopes embryogenesis from
      cleavage through hatching under controlled environmental conditions, including
      detailed descriptions of externally visible morphological features that are
      easily distinguished in either live or freshly fixed embryos under a dissecting
      microscope. Photomicrographs are also provided to aid in the accurate and rapid
      staging of E. scolopes embryos.

PMID- 20150050
TI  - Labeling pinocytotic vesicles and cytoplasm with fluorescent dextrans or ficolls
      for imaging.
AB  - The eukaryotic cell has evolved to compartmentalize its functions and transport
      various metabolites among cellular compartments. Therefore, in cell biology, the
      study of organization and structure/function relationships is of great
      importance. Dextran, a high-molecular-weight poly-D-glucose, and ficoll, a
      synthetic polymer of epichlorhydrin and sucrose, are electroneutral, hydrophilic
      polysaccharides whose size can be varied. This variability in size coupled with
      their membrane impermeability can make them useful for studying fluid-phase
      pinocytosis, the size of membrane pores (e.g., nuclear membrane pores), or the
      environmental conditions and size of a cell compartment. This article presents a
      method for labeling live or fixed cells with substituted forms of dextran or
      ficoll attached to a fluorescent conjugate. In the event that the desired probe
      is not available commercially, this article also provides a method for covalently
      attaching a fluorophore to substituted polysaccharide.

PMID- 20150051
TI  - Phenotypic analysis of Arabidopsis mutants: root elongation under salt/hormone
      induced stress.
AB  - Abiotic stress, such as high salt or low temperature, adversely affects plant
      growth and development. Salt stress inhibits seed germination, retards plant
      growth, and accelerates senescence. Freezing or drought stress can cause cell
      damage and plant death. The following parameters can be used to evaluate plant
      tolerance to salt, drought, or freezing stress: root elongation (described here),
      fresh weight gain, seed germination, electrolyte leakage, or water loss
      measurement. Several stress mutants have been characterized using these tests,
      including hos1 and hos2, which show higher expression of some stress-regulated
      genes when exposed to low-temperature stress; hos5, which shows higher expression
      of some stress-regulated genes under abscisic acid (ABA) and salt treatments; sfr
      mutants, which are deficient in freezing tolerance; and eskimo1, which is
      constitutively freezing-tolerant. To determine whether a mutant shows altered
      response to osmotic stress or to specific ions, various concentrations of salts
      can be used. Mannitol can also be used to impose osmotic stress, and ABA can be
      used to impose hormone stress. Among the salts used in this protocol, Li(+) is
      considered a toxic analog of Na(+), whereas Cs(+) is a toxic cation related to
      K(+). The levels of stress suggested in this protocol may need to be adjusted,
      depending on the ecotype and growth conditions used.

PMID- 20150052
TI  - Preparation of soluble GST fusion proteins.
AB  - A wide variety of plasmid vectors are commercially available for the production
      of fusion proteins in bacterial cells. Most are also designed to incorporate a
      tag that allows affinity purification of the expressed fusion protein from
      bacterial cell extracts. The most commonly used are vectors that incorporate a
      portion of the glutathione-S-transferase (GST) enzyme that is able to bind to
      immobilized glutathione and vectors that use a polyhistidine tag which binds
      immobilized nickel ions with high affinity. This protocol describes preparation
      of a soluble GST fusion protein, isolated using glutathione agarose beads.

PMID- 20150053
TI  - Preparation of insoluble GST fusion proteins.
AB  - A wide variety of plasmid vectors are commercially available for the production
      of fusion proteins in bacterial cells. Most are also designed to incorporate a
      tag that allows affinity purification of the expressed fusion protein from
      bacterial cell extracts. The most commonly used are vectors that incorporate a
      portion of the glutathione-S-transferase (GST) enzyme that is able to bind to
      immobilized glutathione and vectors that use a polyhistidine tag which binds
      immobilized nickel ions with high affinity. This protocol describes preparation
      of an insoluble GST fusion protein, isolated using glutathione agarose beads.

PMID- 20150054
TI  - Imaging synaptogenesis by measuring accumulation of synaptic proteins.
AB  - Synapse formation and modification involve the successive recruitment of pre- and
      post-synaptic signaling molecules. The procedure presented here investigates the
      function of specific synaptic factors in gain- and loss-of-function experiments
      by measuring protein accumulation at synapses using quantitative
      immunohistochemistry, confocal microscopy, and image analysis. Although the
      procedure is described for dissociated cultures of hippocampal neurons, it can be
      extended to various neuronal cell types in culture.

PMID- 20150055
TI  - Imaging action potentials with calcium indicators.
AB  - The understanding of neuronal circuits has been, and will continue to be, greatly
      advanced by the simultaneous imaging of action potentials in neuronal ensembles.
      This protocol describes "bulk" loading of brain slices with acetoxymethyl (AM)
      ester calcium indicators in order to monitor action potential activity in large
      populations of neurons simultaneously. The imaging of calcium influx into neurons
      provides an indirect, but accurate, measure of action potential generation in
      individual neurons. Single-cell resolution, and thus the easy identification of
      every active cell, is the key advantage of the technique.

PMID- 20150056
TI  - Indirect immunofluorescence labeling in the yeast Saccharomyces cerevisiae.
AB  - The budding yeast Saccharomyces cerevisiae is an ideal model system for the
      initial characterization of novel genes and their corresponding gene products.
      Genetic analysis is straightforward, and sophisticated cell biological methods
      are available. Furthermore, only in a genetically tractable organism is it
      possible to use epitope-tagged proteins to the best advantage. In S. cerevisiae,
      it is a trivial matter to determine whether a modified version of a protein is
      functional. This is accomplished by testing whether the tagged protein can
      complement a null phenotype or rescue a conditional phenotype. Methods such as
      indirect immunofluorescence and the use of green fluorescent protein (GFP) allow
      the investigator to correlate the intracellular localization of the protein with
      its function in vivo. This article includes a detailed protocol for performing
      indirect immunofluorescence with S. cerevisiae. Cells are grown exponentially and
      then fixed. After fixation, an enzyme is used to remove the cell wall, and the
      cells are adhered to slides. Subsequent steps involve the application of primary
      and secondary antibodies and the final processing of the slide.

PMID- 20150057
TI  - Bimolecular affinity purification (BAP): tandem affinity purification using two
      protein baits.
AB  - The tandem affinity purification (TAP) procedure was pioneered in yeast for the
      purpose of purifying and characterizing protein complexes. While affinity
      purification is relatively easy to perform, nonspecific protein interactions can
      plague the identification of true interacting partners of the given bait utilized
      in the purification. To alleviate this problem, two sequential affinity
      purification steps are employed in the TAP procedure. Since its inception in
      yeast, TAP has gone through many adaptations and has been employed multiple times
      in diverse organisms, including mammalian systems. In all these approaches, two
      out of many possible affinity moieties are employed and are usually expressed as
      a fusion polypeptide in the amino or carboxyl-terminal region of the protein
      bait. In this protocol, we describe a variation on the TAP procedure in which the
      affinity moieties are placed on two different proteins of a molecular complex to
      isolate or detect components present in the complex. This variation, which we
      refer to as bimolecular affinity purification (BAP), is suited for the
      identification of specific molecular complexes marked by the presence of two
      known components.

PMID- 20150058
TI  - Preparation of genomic DNA from Hawaiian bobtail squid (Euprymna scolopes) tissue
      by cesium chloride gradient centrifugation.
AB  - This procedure describes the extraction of genomic DNA from adult bobtail squid
      (Euprymna scolopes) tissues by cesium chloride (CsCl) gradient centrifugation.
      There are numerous generic methods and commercial kits for the preparation of
      genomic DNA based on proteolytic digestion of chromatin components, followed by
      selective binding of nucleic acids to ion-exchange affinity media, but many of
      these do not yield DNA that can be readily restricted. Also, molluscan tissues
      contain mucopolysaccharides, which tend to copurify with DNA under certain
      conditions. Although nucleic acids prepared this way can serve as a template for
      polymerase chain reaction (PCR), other enzymatic modifications of nucleic acids
      are inhibited by these contaminants. The method described here yields high
      molecular-weight DNA that can be readily restricted for Southern hybridization.
      The procedure uses brain tissue under the assumption that its genome is unlikely
      to be rearranged in any way, has a high nucleic acid:protein ratio, and avoids
      potential sources of enzymatic contaminants and parasites from the intestinal
      sac. However, the method can be applied to other tissue sources and works well
      with other species. The purification of DNA by gradient centrifugation is an
      established method based on the specific buoyant density of double-stranded
      nucleic acids and the ability of CsCl solutions to form a salt gradient in a
      centrifugal field. It can also be adapted to the purification of RNA, which has a
      higher buoyant density than DNA. Unfortunately, this method is somewhat involved
      and expensive and produces large amounts of ethidium bromide waste.

PMID- 20150059
TI  - Confocal immunocytochemistry of embryonic and juvenile Hawaiian bobtail squid
      (Euprymna scolopes) tissues.
AB  - The Hawaiian bobtail squid Euprymna scolopes is a cephalopod whose small size,
      short lifespan, rapid growth, and year-round availability make it suitable as a
      model organism. This protocol describes the preparation of whole juvenile squids
      by whole-mount immunocytochemistry for visualization by confocal microscopy.

PMID- 20150060
TI  - Whole-mount in situ hybridization of Hawaiian bobtail squid (Euprymna scolopes)
      embryos with DIG-labeled riboprobes: I. DNA template preparation and in vitro
      transcription of riboprobes.
AB  - Whole-mount in situ hybridization is a technique used to localize and visualize
      specific gene transcripts in whole embryos by hybridizing labeled RNA probes
      complementary to the sequence of interest. A digoxigenin (DIG)-labeled riboprobe
      synthesized during in vitro transcription through the incorporation of a DIG
      labeled UTP is hybridized to the target sequence under stringent conditions, and
      excess, unhybridized probe is removed during a series of washes. The location of
      the labeled riboprobe, and thus the mRNA sequence of interest, is then visualized
      by immunohistochemistry. This protocol outlines the techniques for preparing RNA
      probes for whole-mount in situ hybridization in Hawaiian bobtail squid (Euprymna
      scolopes) embryos from linearized plasmid DNA or polymerase chain reaction (PCR)
      products.

PMID- 20150061
TI  - Whole-mount in situ hybridization of Hawaiian bobtail squid (Euprymna scolopes)
      embryos with DIG-labeled riboprobes: II. Embryo preparation, hybridization,
      washes, and immunohistochemistry.
AB  - Whole-mount in situ hybridization is a technique used to localize and visualize
      specific gene transcripts in whole embryos by hybridizing labeled RNA probes
      complementary to the sequence of interest. A digoxigenin (DIG)-labeled riboprobe
      synthesized during in vitro transcription through the incorporation of DIG
      labeled UTP is hybridized to the target sequence under stringent conditions, and
      excess unhybridized probe is removed during a series of washes. The location of
      the labeled riboprobe, and thus the mRNA sequence of interest, is then visualized
      by immunohistochemistry. This protocol outlines the steps involved in preparing
      Hawaiian bobtail squid (Euprymna scolopes) embryos, hybridizing a DIG-labeled
      riboprobe in whole-mount embryos, and visualizing the labeled RNA
      colorimetrically using an alkaline-phosphatase-conjugated anti-DIG antibody.

PMID- 20150062
TI  - Culture of Hawaiian bobtail squid (Euprymna scolopes) embryos and observation of
      normal development.
AB  - The ability to rear Hawaiian bobtail squid (Euprymna scolopes) embryos under
      controlled environmental conditions is a basic and necessary tool for
      developmental studies. It negates the need to know when fertilization occurred,
      allows correlation of the phase of development with the time of development
      (thereby facilitating collection of embryos at specific stages), and allows
      comparisons between cephalopod species. Embryonic development in E. scolopes is
      robust over a range of temperatures, is relatively rapid (approximately 21 d),
      and proceeds normally under laboratory conditions at ambient temperature (27
      degrees C-29 degrees C). Here we present methods for maintaining E. scolopes
      embryos in culture from cleavage through hatching, as well as observing and
      recording live or freshly fixed embryos under a dissecting microscope.

PMID- 20150063
TI  - Yam (Dioscorea) husbandry: cultivating yams in the field or greenhouse.
AB  - This protocol describes how to cultivate yams (Dioscorea) in the field or
      greenhouse. It refers especially to the tropical food species but it will also
      work for temperate species. The tropical food species of Dioscorea grow in warm,
      sunny climates with temperatures between 25 degrees C and 30 degrees C. Short
      days of 10-11 h result in tuber formation, while days longer than 12 h favor vine
      growth. Yams require deep, loose, textured loamy soil that is rich in organic
      matter. They are best planted at the beginning of the rainy season. Mulch around
      the planted sets protects them from excessive heat and desiccation, especially in
      areas with hot temperatures and dry weather. It also adds organic matter to the
      soil, prevents soil erosion, preserves water in the soil, and increases microbial
      activity in the soil. Yams do not tolerate waterlogged conditions. It is
      important to stake the plants to allow full exposure of their leaves to light for
      photosynthetic activity and to reduce disease.

PMID- 20150064
TI  - Culturing meristematic tissue and node cuttings from yams (Dioscorea).
AB  - This protocol describes how to produce whole yam (Dioscorea) plantlets in vitro
      through yam meristem culture and from yam node cuttings.

PMID- 20150065
TI  - Post-flask management of yam (Dioscorea) plantlets.
AB  - This protocol describes how to harden or acclimatize tissue culture-derived yam
      (Dioscorea) plantlets before transplanting them in the soil. Briefly, the
      plantlets are first put in pots with a vermiculite and peat moss mixture, and the
      pots are placed in a humidity chamber, where they are sprayed and watered daily.
      After 2 wk, the plants are transplanted to pots or plastic bags with ordinary or
      sterile soil and watered daily. After another 2 wk, they are transplanted into
      the field.

PMID- 20150066
TI  - Producing yam (Dioscorea) seeds through controlled crosses.
AB  - This protocol describes how to produce yam (Dioscorea) seeds through controlled
      pollination of flowers on female plants. Pollination by flower thrips takes place
      naturally in normal yam-growing environments in the presence of flowering male
      and female genotypes, although it is not efficient. This protocol leads to the
      production of hybrid seeds of known parentage for genetic studies and use in
      breeding programs.

PMID- 20150067
TI  - Extraction of DNA from yam (Dioscorea) leaves.
AB  - This protocol describes how to extract DNA from the leaves of true yams
      (Dioscorea) for polymerase chain reaction (PCR) and other analyses.

PMID- 20150068
TI  - Nuclear run-on assay.
AB  - The nuclear run-on assay was developed as a method for establishing that the
      transcription initiation rate contributes to the regulated expression of
      mammalian genes. The difference between monitoring gene expression by the nuclear
      run-on assay versus most other assays is that the nuclear run-on assay provides a
      measure of the frequency of transcription initiation and is largely independent
      of the effects of RNA stability. It can also be used to determine whether
      polymerase pausing or attenuation contributes to gene regulation. Briefly, the
      nuclear run-on assay begins with samples of cells that contain different steady
      state amounts of the mRNA or protein of interest. The cells are chilled, and the
      plasmid membranes are permeabilized or lysed. These steps result in polymerase
      pausing. The nuclei are then incubated for a short time at 37 degrees C in the
      presence of nucleoside triphosphates (NTPs) and radiolabeled uridine 5'
      triphosphate (UTP). New transcripts are not initiated during this incubation, but
      the radiolabeled nucleotide becomes incorporated into transcripts that were being
      synthesized when the cells were first chilled and lysed. The number of nascent
      transcripts on the gene at the time of chilling is thought to be proportional to
      the frequency of transcription initiation. To determine the relative number of
      nascent transcripts in each sample, the radiolabeled RNA is purified and
      hybridized to a membrane containing immobilized DNA from the gene of interest.
      The amount of radioactivity that hybridizes to the membrane is approximately
      proportional to the number of nascent transcripts.

PMID- 20150073
TI  - Assessing human variation data for signatures of natural selection.
AB  - In this article, we highlight some of the different types of natural selection,
      their effects on patterns of DNA variation, and some of the statistical tests
      that are commonly used to detect such effects. We also explain some of the
      relative strengths and weaknesses of different strategies that can be used to
      detect signatures of natural selection at individual loci. These strategies are
      illustrated by their application to empirical data from gene variants that are
      often associated with differences in disease susceptibility. We briefly outline
      some of the methods proposed to scan the genome for evidence of selection.
      Finally, we discuss some of the problems associated with identifying signatures
      of selection and with making inferences about the nature of the selective
      process.

PMID- 20150074
TI  - Laboratory methods for high-throughput genotyping.
AB  - The genetics of complex diseases has been given a tremendous boost in recent
      years by the introduction of high-throughput laboratory methods that make it
      possible to approach larger questions in larger populations and to cover the
      genome more comprehensively. The ability to determine genotypes of many
      individuals accurately and efficiently has allowed genetic studies that cover
      more of the variation within individual genes, instead of focusing only on one or
      a few coding variants, and to do so in study samples of reasonable power. Chip
      based genotyping assays, combined with knowledge of the patterns of coinheritance
      of markers (linkage disequilibrium [LD]), have stimulated genome-wide association
      studies (GWAS) of complex diseases. Recent successes of GWAS in identifying
      specific genes that affect risk for common diseases are dramatic illustrations of
      how improved technology can lead to scientific breakthroughs. A key issue in high
      throughput genotyping is to choose the appropriate technology for your goals and
      for the stage of your experiment, being cognizant of your sample numbers and
      resources. This article introduces some of the commonly used methods of high
      throughput single-nucleotide polymorphism (SNP) genotyping for different stages
      of genetic studies and briefly reviews some of the high-throughput sequencing
      methods just coming into use. It also mentions some recent developments in "next
      generation" sequencing that will enable other kinds of studies. This article is
      not intended to be comprehensive, and because technology in this area is rapidly
      changing, our comments should be taken as a starting point for further
      investigation.

PMID- 20150075
TI  - The tammar wallaby, Macropus eugenii: a model kangaroo for the study of
      developmental and reproductive biology.

PMID- 20150076
TI  - The sea squirt Ciona intestinalis.

PMID- 20150077
TI  - Dignam and Roeder nuclear extract preparation.

PMID- 20150078
TI  - In vitro transcription using HeLa cell extracts and primer extension.

PMID- 20150079
TI  - Working with tammar wallabies (Macropus eugenii).

PMID- 20150080
TI  - Performing surgery on tammar wallaby (Macropus eugenii) adults.

PMID- 20150081
TI  - Surgery on tammar wallaby (Macropus eugenii) pouch young.

PMID- 20150082
TI  - Collection, handling, fixation, and processing of tammar wallaby (Macropus
      eugenii) embryos.

PMID- 20150083
TI  - Culturing tammar wallaby (Macropus eugenii) pouch young gonads.

PMID- 20150084
TI  - Culturing tammar wallaby (Macropus eugenii) peri-gastrulation stage embryos.

PMID- 20150085
TI  - Immunohistochemical staining of sectioned tammar wallaby (Macropus eugenii)
      tissue.

PMID- 20150086
TI  - Whole-mount immunohistochemical staining of tammar wallaby (Macropus eugenii)
      cleavage stages and blastocysts.

PMID- 20150087
TI  - Whole-mount immunohistochemical staining of tammar wallaby (Macropus eugenii)
      peri-gastrulation embryos.

PMID- 20150088
TI  - Analyzing microorganisms in environmental samples using stable isotope probing
      with H2(18)O.

PMID- 20150089
TI  - Amplification of bisulfite-converted DNA for genome-wide DNA methylation
      profiling.

PMID- 20150091
TI  - Isolation of sea squirt (Ciona) gametes, fertilization, dechorionation, and
      development.

PMID- 20150090
TI  - Biarsenical labeling of tetracysteine-tagged proteins for tracking existing and
      newly synthesized pools of proteins.

PMID- 20150092
TI  - Electroporation of transgenic DNAs in the sea squirt Ciona.

PMID- 20150093
TI  - X-gal staining of electroporated sea squirt (Ciona) embryos.

PMID- 20150094
TI  - Microinjection of morpholino oligos and RNAs in sea squirt (Ciona) embryos.

PMID- 20150095
TI  - Whole-mount in situ hybridization on sea squirt (Ciona intestinalis) embryos.

PMID- 20150096
TI  - Isolation of individual cells and tissues from electroporated sea squirt (Ciona)
      embryos by fluorescence-activated cell sorting (FACS).

PMID- 20150100
TI  - Fluorescent protein tracking and detection: fluorescent protein structure and
      color variants.

PMID- 20150101
TI  - Fluorescent protein tracking and detection: applications using fluorescent
      proteins in living cells.

PMID- 20150102
TI  - Computational image analysis of cellular dynamics: a case study based on particle
      tracking.

PMID- 20150103
TI  - Genome-wide association studies.

PMID- 20150104
TI  - The rabbit (Oryctolagus cuniculus): a model for mammalian reproduction and early
      embryology.

PMID- 20150105
TI  - Paramecium tetraurelia: the renaissance of an early unicellular model.

PMID- 20150106
TI  - Measurement of free Ca2+ concentration in the lumen of neuronal endoplasmic
      reticulum.

PMID- 20150107
TI  - Phloroglucinol stain for lignin.

PMID- 20150108
TI  - Phenotypic analysis of Arabidopsis mutants: electrolyte leakage after freezing
      stress.

PMID- 20150109
TI  - Rabbit mating and embryo isolation.

PMID- 20150110
TI  - Dissection and fixation of rabbit embryos.

PMID- 20150111
TI  - Live rabbit embryo culture.

PMID- 20150112
TI  - Staining and imaging of live rabbit embryos.

PMID- 20150113
TI  - Whole-mount in situ immunofluorescence of early rabbit embryos.

PMID- 20150114
TI  - Whole-mount in situ hybridization of early rabbit embryos.

PMID- 20150115
TI  - Mounting, embedding, and sectioning of early rabbit embryos.

PMID- 20150116
TI  - Embryo transfer in rabbits.

PMID- 20150117
TI  - Artificial insemination in rabbits.

PMID- 20150119
TI  - Cryopreservation of rabbit embryos.

PMID- 20150118
TI  - Artificial fertilization in rabbits by intracytoplasmic sperm injection (ICSI).

PMID- 20150120
TI  - Maintaining clonal Paramecium tetraurelia cell lines of controlled age through
      daily reisolation.

PMID- 20150121
TI  - Mass culture of Paramecium tetraurelia.

PMID- 20150122
TI  - Silencing specific Paramecium tetraurelia genes by feeding double-stranded RNA.

PMID- 20150123
TI  - DNA microinjection into the macronucleus of paramecium.

PMID- 20150124
TI  - Immunocytochemistry of Paramecium cytoskeletal structures.

PMID- 20150125
TI  - Fluorescence in situ hybridization for the identification of environmental
      microbes.

PMID- 20150127
TI  - Using the metagenomics RAST server (MG-RAST) for analyzing shotgun metagenomes.

PMID- 20150126
TI  - Preparation and culture of limb blastema stem cells from regenerating larval and
      adult salamanders.

PMID- 20150128
TI  - Dual-color ELISPOT assay for the simultaneous detection of IL-2 and/or IFN-gamma
      secreting T cells.

PMID- 20150129
TI  - Cryosectioning and immunocytochemistry of adult Drosophila eye sections.

PMID- 20150133
TI  - Calculating linear flow velocity from volumetric flow rate.

PMID- 20150134
TI  - Visualizing fetal mouse vasculature by India ink injection.

PMID- 20150135
TI  - Calcium phosphate transfection of 3T3 fibroblasts.

PMID- 20150136
TI  - DEAE-dextran transfection of lymphocyte cell lines.

PMID- 20150137
TI  - Transfection by electroporation of RAW 264.7 macrophages.

PMID- 20150138
TI  - Preparation of the gel and column for chromatofocusing.

PMID- 20150139
TI  - Preparation of the sample for chromatofocusing: buffer exchange and desalting.

PMID- 20150140
TI  - Purification of proteins by chromatofocusing.

PMID- 20150141
TI  - Removal of elution buffer from protein sample fractions after chromatofocusing.

PMID- 20150142
TI  - Cleaning, regeneration, and storage of chromatofocusing columns.

PMID- 20150143
TI  - BiFC imaging assay for plant protein-protein interactions.

PMID- 20150144
TI  - Four-dimensional imaging of plant cells during the cell cycle.

PMID- 20150145
TI  - Analysis of gene expression by in situ hybridization on adult zebrafish brain
      sections.

PMID- 20150146
TI  - Purification of genomic DNA extracted from environmental sources for use in a
      polymerase chain reaction.

PMID- 20150147
TI  - DNase-seq: a high-resolution technique for mapping active gene regulatory
      elements across the genome from mammalian cells.

PMID- 20150148
TI  - Genome-wide analysis of DNA synthesis by BrdU immunoprecipitation on tiling
      microarrays (BrdU-IP-chip) in Saccharomyces cerevisiae.

PMID- 20150149
TI  - Analysis of nonsense-mediated mRNA decay by monitoring mRNA half-lives in
      mammalian cells.

PMID- 20150163
TI  - Chromatofocusing.

PMID- 20150164
TI  - Live cell imaging of plants.

PMID- 20150165
TI  - Linkage analysis of discrete traits.

PMID- 20150166
TI  - Salt intake induces epithelial-to-mesenchymal transition of the peritoneal
      membrane in rats.
AB  - BACKGROUND: Dietary salt intake has been linked to hypertension and
      cardiovascular disease through volume-mediated effects. Accumulating evidence
      points to direct negative influence of salt intake independent of volume
      overload, such as cardiac and renal fibrosis, mediated through transforming
      growth factor beta (TGF-beta). Epithelial-to-mesenchymal transition (EMT) has
      been implicated as a key process in chronic fibrotic diseases, such as chronic
      kidney disease or heart failure. The potential role of dietary salt intake on
      cell transdifferentiation has never been investigated. This study analysed the
      effect of dietary salt intake on EMT and fibrosis in the peritoneal membrane (PM)
      in a rat model. METHODS: Twenty-eight Wistar rats were randomized to a normal
      salt (NS) or a high salt (HS) intake. NS and HS rats had free access to tap water
      or NaCl 2% as drinking water, respectively. After 2 weeks, samples of peritoneum
      were taken, and TGF-beta(1), Interleukin 6 (IL-6) and vascular endothelial growth
      factor (VEGF) mRNA expression were quantified with qRT-PCR. Fibrosis and
      submesothelial PM thickness were scored. EMT was evaluated using fluorescence
      staining with cytokeratin and alpha smooth muscle actin (alpha-SMA). RESULTS:
      Dietary salt intake caused peritoneal fibrosis and thickening of the
      submesothelial layer and induced EMT as identified by colocalization of
      cytokeratin and alpha-SMA in cells present in the submesothelial layer.
      Peritoneal TGF-beta(1) and IL-6 mRNA expression were upregulated in the HS group.
      CONCLUSION: High dietary salt intake induces EMT and peritoneal fibrosis, a
      process coinciding with upregulation of TGF-beta1.

PMID- 20150167
TI  - Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice.
AB  - BACKGROUND: Podocytes play an important role in maintaining normal glomerular
      function. A podocyte-specific conditional knockout technology has been
      established by the use of transgenic mice expressing a podocyte-specific Cre
      recombinase to clarify the role of genes expressed in the podocytes. However, it
      may be difficult to examine the role of genes in certain pathologic conditions
      using conventional podocyte-specific knockout mice because they may be
      embryonically lethal or exhibit congenital renal abnormality. METHODS: To
      introduce a temporal control in the genetic experiments targeting the podocyte,
      we constructed tamoxifen-inducible Cre recombinase (CreER(T2)) transgenic mice
      under the control of podocyte-specific promoter, 2.5-kb fragment of the human
      podocin (NPHS2) gene. The specificity and efficiency of Cre activity were
      examined by crossing NPHS2-CreER(T2) with the ROSA26 reporter (R26R) mouse in
      which a floxed-stop cassette has been placed upstream of the beta-galactosidase
      gene. Four-week-old double-mutant mice (NPHS2-CreER(T2)/R26R) were
      intraperitoneally administered with 0.5 mg of 4-hydroxytamoxifen (4-OHT) for
      three consecutive days. RESULTS: NPHS2-CreER(T2)/R26R treated with 4-OHT
      expressed beta-galactosidase specifically in 85% of the podocytes in glomeruli.
      Expression of Cre recombinase mRNA was mostly restricted to the kidney,
      especially in glomeruli. CONCLUSIONS: In conclusion, we have successfully
      generated podocyte-specific inducible Cre transgenic mice by tamoxifen
      administration. These mice allow us to disrupt the genes specifically in the
      podocytes after birth.

PMID- 20150168
TI  - Circulating monocyte subpopulations with high expression of angiotensin
      converting enzyme predict mortality in patients with end-stage renal disease.
AB  - BACKGROUND: Circulating monocytes can be divided into distinct populations
      according to their expression of surface markers CD14 and CD16. In patients with
      chronic kidney disease (CKD), the cell fraction expressing high levels of CD14
      and CD16 is expanded and the numbers of these cells are predictive for
      cardiovascular disease. The present pilot study describes the predictive role of
      a combined biomarker consisting of high numbers of CD14(++)CD16(+) cells together
      with high expression of angiotensin-converting enzyme (ACE) on these cells for
      mortality in CKD Stage V(D) (dialysis) patients. METHODS: In a prospective
      observational study, monocyte subpopulations were enumerated and ACE expression
      was quantified in 74 CKD patients by flow cytometry. Patients were assigned to
      one of four groups according to monocyte population numbers and ACE expression
      below and above the respective medians and observed for mortality and
      cardiovascular events for 46 months. RESULTS: Patients stratified to the 'high
      CD14(++)CD16(+), high ACE' group (n = 22) had a dramatically enhanced mortality
      of 70% at 2 years compared to all other patient groups (mortality 14.8%, HR 4.86
      [95% CI 2.17-10.86, P < 0.0001]). Atherosclerosis-associated events predominated
      among the causes of death. CONCLUSIONS: This study describes a new combined
      biomarker of monocyte subpopulation numbers together with high expression of ACE
      that has a striking predictive value for mortality of CKD patients. Further
      research into the pathophysiologic background of this observation is warranted.

PMID- 20150169
TI  - Progressive glomerulopathy with unusual deposits of striated structures: a new
      disease entity?
AB  - A 68-year-old man developed proteinuria and renal insufficiency. A renal biopsy
      showed mesangial proliferation and double contour in almost all glomeruli. Congo
      red staining for amyloid was negative. Immunofluorescence microscopy revealed no
      deposition of immunoglobulins. Electron microscopy showed unusual deposits of
      striated structures mainly in the subendothelial space and the mesangium. These
      deposits contained regularly stacked straight electron-dense bands. Microfilament
      like deposits were also observed. The patient did not respond to steroid therapy
      and developed end-stage renal disease. All known disease entities with non
      amyloid non-immunoglobulin-derived organized glomerular deposits were excluded.
      Progressive glomerulopathy in our patient might be a new disease entity.

PMID- 20150170
TI  - Twelve-month follow-up results from a randomized controlled trial of a brief
      personalized feedback intervention for problem drinkers.
AB  - AIMS: To examine the impact of a web-based personalized feedback intervention,
      the Check Your Drinking (CYD; www.CheckYourDrinking.net) screener at 12-month
      follow-up. METHODS: Respondents (N = 185) were recruited from a general
      population telephone survey of Ontario, Canadian adults (> or =18 years) by
      asking risky drinkers if they were willing to help develop and evaluate Internet
      based interventions for drinkers. Those randomly assigned to the intervention
      condition were provided with the web address and a unique password to a study
      specific copy of the CYD. Respondents assigned to the control condition were sent
      a written description of the different components of the CYD and asked how useful
      they thought each of the components might be. Respondents were followed up at 3,
      6 and 12 months. RESULTS: By the 12-month follow-up, the impact of the
      intervention previously reported at 3 and 6 months of CYD on problem drinkers'
      alcohol consumption was no longer apparent (P > 0.05). CONCLUSIONS: Recognizing
      that many people with alcohol concerns will never seek treatment, recent years
      have seen an increase in efforts to find ways to take treatment to problem
      drinkers. The CYD is one such intervention that has a demonstrated effect on
      reducing alcohol consumption in the short term (i.e. 6 months). Other more
      intensive Internet-based interventions or interventions via other modalities may
      enhance this positive outcome over the short and long term among problem drinkers
      who would be otherwise unlikely to access treatment for their alcohol concerns.

PMID- 20150171
TI  - The PFO anatomy evaluation as possible tool to stratify the associated risks and
      the benefits arising from the closure.
AB  - AIMS: According to the current guidelines, the patent foramen ovale (PFO) is
      still considered a qualitative factor and, as a consequence, its closure is
      recommended just on the basis of its 'presence'. METHODS AND RESULTS: In the year
      2008, we evaluated 25 patients (mean age 62.7) with acute cerebrovascular event
      and 92 patients (mean age 27.3) suffering from migraine with aura. No PFO was
      reported in 79 patients. A venous-to-arterial circulation shunt had been shown in
      38 patients (29 subjects with migraine and 9 subjects with prior stroke).
      According to the number of microbubbles arrived during the Valsava manoeuvre, we
      found: 25 small PFO, 6 moderate PFO, and 6 severe PFO. In the baseline population
      with migraine (n = 92), 32% (n = 29) had a PFO. A 'large' foramen was reported in
      approximately 9% of the migraine subjects. In the population with prior stroke
      (n=25), 9 patients (36%) had a PFO. A 'large' foramen was reported in 45% of the
      patients with ischaemic stroke. We found embryonic recesses in 13% (n = 4) of the
      patients with migraine and PFO (n=29) vs. 66% (n=6) of the patients with
      ischaemic stroke and PFO (P= 0.01). CONCLUSION: It is possible to suppose that
      not all PFO have the same prognostic value. The evaluation of two anatomical
      characteristics can allow to identify those foramina at higher risk and, as a
      consequence, the patients who could have a major benefit from the closure.

PMID- 20150172
TI  - Serum high-sensitivity C-reactive protein and heat shock protein 27 antibody
      titers in patients with stroke and 6-month prognosis.
AB  - Serum heat shock protein 27 immunoglobulin G (IgG) antibody titers (anti-HSP27)
      and high-sensitivity C-reactive protein (hsCRP) concentrations were measured in
      samples from 168 patients in the first 24 hours after the onset of stroke and 80
      age-and sex-matched control participants. In patients with stroke, median serum
      anti-HSP27 titer was significantly higher than that of the control group (0.18
      [0.14-0.28] vs 0.08 [0.04-0.12], P < .001). Median serum hsCRP concentration was
      also significantly higher in patients compared with the control group (11.43
      [8.07-13.53] vs 3.23 [1.66-6.24], P < .001). Serum anti-HSP27 and hsCRP
      concentrations did not differ significantly among patients with different stroke
      types. Neither serum anti-HSP27 nor hsCRP levels predicted 6-month prognosis in
      the patients with stroke. We conclude that serum anti-HSP27 titers and hsCRP
      concentrations are elevated in patients with stroke but do not distinguish
      between stroke types or predict 6-month prognosis.

PMID- 20150173
TI  - The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling
      mechanism for a complex, chronic immunological condition.
AB  - BACKGROUND: Endometriosis is an inflammatory condition, associated with highly
      dysregulated immune response at both uterine and peritoneal levels. Surprisingly,
      Foxp3+ regulatory T-cells, which control and suppress a range of immune
      responses, have not previously been investigated in endometriosis. METHODS AND
      RESULTS: Immunohistochemical analysis of Foxp3+ cells in 127 eutopic endometrial
      samples and 59 ectopic peritoneal lesions revealed that these immune cell
      populations are highly disturbed in women suffering from endometriosis. We showed
      that Foxp3+ cells remained highly up-regulated during the secretory phase of the
      menstrual cycle, while at this time their expression is significantly down
      regulated in women without endometriosis (P < 0.001). Foxp3+ cells were detected
      in the stroma of 18 of the 59 peritoneal endometriotic lesions, but not in the
      surrounding or control peritoneal tissue. CONCLUSIONS: We propose that in eutopic
      endometrium in women with endometriosis Foxp3+ cells decrease the ability of
      newly recruited immune cell populations to effectively recognize and target
      endometrial antigens shed during menstruation, allowing their survival and
      ability to implant in ectopic sites. At these ectopic sites, variable expression
      of Foxp3+ cells within some peritoneal endometriotic lesions is likely to be
      linked to the characteristics and stage of individual lesion development and be
      playing key roles in pathogenesis and progression of this unique condition.

PMID- 20150174
TI  - Effects of menstrual cycle phase on metabolomic profiles in premenopausal women.
AB  - BACKGROUND: Characterization of the normal degree of physiological variation in
      the metabolomic profiles of healthy humans is a necessary step in the development
      of metabolomics as both a clinical research and diagnostic tool. This study
      investigated the effects of the menstrual cycle on (1)H nuclear magnetic
      resonance (NMR) derived metabolomic profiles of urine and plasma from healthy
      women. METHODS: In this study, 34 healthy women were recruited and a first void
      urine and fasting blood sample were collected from each woman at four different
      time points during one menstrual cycle. Serum hormone levels were used in
      combination with the menstrual calendar to classify the urine and plasma samples
      into five different phases i.e. menstrual, follicular, periovulatory, luteal and
      premenstrual. The urine and plasma samples were analysed using (1)H NMR
      spectroscopy and subsequent data were analysed using principal component analysis
      (PCA) and partial least squares discriminant analysis. RESULTS: PCA of the urine
      spectra showed no separation of samples based on the phases of the menstrual
      cycle. Multivariate analysis of the plasma spectra showed a separation of the
      menstrual phase and the luteal phase samples (R(2) = 0.61, Q(2) = 0.41).
      Subsequent analysis revealed a significant decrease in levels of glutamine,
      glycine, alanine, lysine, serine and creatinine and a significant increase in
      levels of acetoacetate and very low density lipoprotein (VLDL CH(2)) during the
      luteal phase. CONCLUSIONS: These results establish a need to control for
      metabolic changes that occur in plasma due to the menstrual cycle in the design
      of future metabolomic studies involving premenopausal women.

PMID- 20150175
TI  - Magnetic-activated cell sorting for sperm preparation reduces spermatozoa with
      apoptotic markers and improves the acrosome reaction in couples with unexplained
      infertility.
AB  - BACKGROUND: Couples with unexplained infertility (UI) tend to have low
      fertilization rates with current IVF procedures. Here, we attempted to identify
      spermatozoa with apoptotic markers in couples with UI and unsuccessful
      intrauterine insemination (IUI) and we investigated the efficiency and benefit of
      magnetic-activated cell sorting (MACS) for sperm preparation in such patients.
      METHODS: Sixty couples with UI and two IUI failures were recruited. The sperm
      were prepared by conventional density gradient centrifugation (DGC) and divided
      into two aliquots. One aliquot was used as a control and the other was further
      processed by MACS (D + M). Apoptotic markers were identified using fluorescence
      labeled dye and flow cytometry, including externalization of phosphatidylserine
      (EPS), disrupted mitochondrial membrane potential (MMP) and DNA fragmentation.
      The fertilization potential of prepared spermatozoa was analyzed by basic semen
      analysis, computer-aided sperm analysis and the induced acrosome reaction test
      (IART). RESULTS: After DGC, spermatozoa showed 18.6% EPS, 28.3% disrupted MMP and
      13.5% DNA fragmentation. Numbers of spermatozoa with apoptotic markers were
      significantly reduced by D + M, versus DGC alone (P < 0.001). Although the
      motility of spermatozoa was slightly decreased after MACS, most sperm motion
      characteristics were not impaired. Interestingly, the IART significantly improved
      after D + M, versus DGC alone, especially for the couples with a normal hemizona
      assay (P < 0.001). CONCLUSIONS: The spermatozoa prepared by D + M showed a
      reduced level of apoptotic markers. Improvement in the IART suggests a high
      fertilization potential of the processed spermatozoa. The identification of
      apoptotic markers and use of MACS may be helpful in directing the management plan
      for patients with UI and multiple IUI failures.

PMID- 20150176
TI  - Mental capacity at the margin: the interface between two acts.

PMID- 20150177
TI  - Structures of a minimal human CFTR first nucleotide-binding domain as a monomer,
      head-to-tail homodimer, and pathogenic mutant.
AB  - Upon removal of the regulatory insert (RI), the first nucleotide binding domain
      (NBD1) of human cystic fibrosis transmembrane conductance regulator (CFTR) can be
      heterologously expressed and purified in a form that remains stable without
      solubilizing mutations, stabilizing agents or the regulatory extension (RE). This
      protein, NBD1 387-646(Delta405-436), crystallizes as a homodimer with a head-to
      tail association equivalent to the active conformation observed for NBDs from
      symmetric ATP transporters. The 1.7-A resolution X-ray structure shows how ATP
      occupies the signature LSGGQ half-site in CFTR NBD1. The DeltaF508 version of
      this protein also crystallizes as a homodimer and differs from the wild-type
      structure only in the vicinity of the disease-causing F508 deletion. A slightly
      longer construct crystallizes as a monomer. Comparisons of the homodimer
      structure with this and previously published monomeric structures show that the
      main effect of ATP binding at the signature site is to order the residues
      immediately preceding the signature sequence, residues 542-547, in a conformation
      compatible with nucleotide binding. These residues likely interact with a
      transmembrane domain intracellular loop in the full-length CFTR channel. The
      experiments described here show that removing the RI from NBD1 converts it into a
      well-behaved protein amenable to biophysical studies yielding deeper insights
      into CFTR function.

PMID- 20150178
TI  - Modification of pancreatic lipase properties by directed molecular evolution.
AB  - Cystic fibrosis is associated with pancreatic insufficiency and acidic
      intraluminal conditions that limit the action of pancreatic enzyme replacement
      therapy, especially that of lipase. Directed evolution combined with rational
      design was used in the aim of improving the performances of the human pancreatic
      lipase at acidic pH. We set up a method for screening thousands of lipase
      variants for activity at low pH. A single round of random mutagenesis yielded one
      lipase variant with an activity at acidic pH enhanced by approximately 50% on
      medium- and long-chain triglycerides. Sequence analysis revealed two
      substitutions (E179G/N406S) located in specific regions, the hydrophobic groove
      accommodating the sn-1 chain of the triglyceride (E179G) and the surface loop
      that is likely to mediate lipase/colipase interaction in the presence of lipids
      (N406S). Interestingly, these two substitutions shifted the chain-length
      specificity of lipase toward medium- and long-chain triglycerides. Combination of
      those two mutations with a promising one at the entrance of the catalytic cavity
      (K80E) negatively affected the lipase activity at neutral pH but not that at
      acidic pH. Our results provide a basis for the design of improved lipase at
      acidic pH and identify for the first time key residues associated with chain
      length specificity.

PMID- 20150179
TI  - Generation of a high-affinity Fcgamma receptor by Ig-domain swapping between
      human CD64A and CD16A.
AB  - A recombinant soluble version of the human high-affinity receptor for IgG, rh
      FcgammaRIA or CD64A, was expressed in mammalian cells and purified from their
      conditioned media. As assessed by circular dichroism, size exclusion
      chromatography and dynamic light scattering, incubation of rh-FcgammaRIA at 37
      degrees C resulted in time-dependent formation of soluble aggregates caused by
      protein unfolding and loss of native structure. Aggregate formation was
      irreversible, temperature-dependent and was independent of rh-FcgammaRIA
      concentration. Aggregated rh-FcgammaRIA lost its ability to inhibit immune
      complex precipitation and failed to bind to IgG-Sepharose. Addition of human IgG1
      to rh-FcgammaRIA prior to incubation at 37 degrees C blocked the formation of rh
      FcgammaRIA aggregates. Production of soluble monomeric rh-FcgammaRIA was limited
      by aggregate formation during cell culture. Substitution of the membrane distal
      D1 Ig domain of FcgammaRIA with the D1 Ig domain of FcgammaRIIIA or CD16A
      resulted in a chimeric receptor, FcgammaR3A1A, with enhanced temperature
      stability. Relative to native rh-FcgammaRIA, FcgammaR3A1A exhibited less
      aggregation in Chinese hamster ovary cell-conditioned media or when purified
      receptor was incubated for up to 24 h at 37 degrees C. Both receptors bound to
      immobilized human IgG1 with high affinity and were equipotent at blockade of
      immune complex-mediated cytokine production from cultured mast cells. Equivalent
      dose-dependent reductions in edema and neutrophil infiltration in the cutaneous
      Arthus reaction in mice were noted for rh-FcgammaRIA and FcgammaR3A1A. These data
      demonstrate that the D1 Ig domains of FcgammaRIA and FcgammaRIIIA are
      functionally interchangeable and further suggest that the chimeric receptor
      FcgammaR3A1A is an effective inhibitor of type III hypersensitivity in mice.

PMID- 20150180
TI  - Introducing antigen-binding sites in structural loops of immunoglobulin constant
      domains: Fc fragments with engineered HER2/neu-binding sites and antibody
      properties.
AB  - Yeast surface display libraries of human IgG1 Fc regions were prepared in which
      loop sequences at the C-terminal tip of the CH3 domain were randomized. A high
      percentage of these library members bound to soluble CD64 and Protein A
      indicating that the randomization step did not grossly interfere with the overall
      structure of the displayed Fc. Sorting these libraries by FACS for binders
      against HER2/neu yielded antigen-specific Fc binders (Fcab; Fc antigen binding)
      of which one was affinity matured, resulting in Fcab clone H10-03-6 which showed
      >10-fold improvement in antigen-binding activity versus the parental clone. Pre
      equilibrium surface plasmon resonance experiments revealed a K(D) value of 69 nM.
      H10-03-6 did not react with other members of the HER family and specifically
      interacted with HER2-positive but not with HER2-negative cells. Importantly, Fcab
      H10-03-6 elicited potent antibody-dependent cellular cytotoxicity in vitro.
      Finally, the in vivo half-life in mice was similar to wild-type Fc indicating
      that the amino acid changes in the CH3 domain did not affect the pharmacokinetic
      behavior of the recombinant Fc. Our data demonstrate that the Fcab scaffold
      combines all features of normal antibodies in a small 50 kD homodimeric protein:
      antigen binding, effector functions and long half-life in vivo.

PMID- 20150181
TI  - Linezolid use for treatment of multidrug-resistant and extensively drug-resistant
      tuberculosis, New York City, 2000-06.
AB  - Rationale Linezolid may be effective for the treatment of multidrug-resistant
      (MDR) and extensively drug-resistant (XDR) tuberculosis (TB); however, serious
      adverse events are common and there is little information on the management of
      these toxicities. METHODS: We retrospectively reviewed public health and medical
      records of 16 MDR TB patients, including 10 patients with XDR TB, who were
      treated with linezolid in New York City between January 2000 and December 2006,
      to determine treatment outcomes and describe the incidence, management and
      predictors of adverse events. RESULTS: Linezolid was added to MDR TB regimens for
      a median duration of 16 months (range: 1-29). Eleven patients (69%) completed
      treatment, four (25%) died and one (6%) discontinued treatment without relapse.
      Myelosuppression occurred in 13 (81%) patients a median of 5 weeks (range: 1-11)
      after starting linezolid, gastrointestinal adverse events occurred in 13 (81%)
      patients after a median of 8 weeks (range: 1-57) and neurotoxicity occurred in
      seven (44%) patients after a median of 16 weeks (range: 10-111). Adverse events
      were managed by combinations of temporary suspension of linezolid, linezolid dose
      reduction and symptom management. Five (31%) patients required eventual
      discontinuation of linezolid. Myelosuppression was more responsive to clinical
      management strategies than was neurotoxicity. Leucopenia and neuropathy occurred
      more often in males and older age was associated with thrombocytopenia (P <
      0.05). CONCLUSIONS: The majority of MDR TB patients on linezolid had favourable
      treatment outcomes, although treatment was complicated by adverse events that
      required extensive clinical management.

PMID- 20150182
TI  - Factors associated with proviral DNA HIV-1 tropism in antiretroviral therapy
      treated patients with fully suppressed plasma HIV viral load: implications for
      the clinical use of CCR5 antagonists.
AB  - OBJECTIVES: Most treated HIV-1 patients have undetectable viral loads and the
      strategies for managing long-term side effects may involve a new class of
      antiretroviral-like CCR5 antagonists. Tropism determination based on proviral DNA
      sequence is necessary for patients with a fully suppressed plasma viral load, as
      assays analysing DNA phenotypes have yet to be developed. We aimed to analyse HIV
      1 tropism using proviral DNA sequencing and the associated factors, in a group of
      patients on antiretroviral (ARV) treatment with an undetectable viral load in
      plasma. METHODS: Blood samples of 140 HIV-1-infected ARV-treated patients with a
      plasma viral load of <40 copies/mL were studied. All patients had never been
      treated with CCR5 antagonists. Co-receptor usage was determined using proviral
      DNA from the V3 env region sequence by Geno2Pheno (false positive rate 10%) and
      PSSM algorithms. RESULTS: Among 140 patients treated using ARV therapy with a
      fully suppressed plasma viral load, at least 70% of patients had proviral R5
      tropic virus. Among all the studied factors (time since HIV infection diagnosis,
      treatment duration, time since viral load undetectability, HIV subtype, current
      treatment, age, number of treatment types, sex, genotypic susceptibility score,
      and nadir and current CD4 cell counts), nadir CD4 T cell count alone was
      associated with tropism during a multivariate analysis. R5X4/X4 tropism was
      present in all nadir CD4 categories. CONCLUSIONS: Proviral DNA tropism
      determination should be required, even for patients with a CD4 nadir cell count
      >350 cells/mm(3), before CCR5 antagonists are used in patients with a fully
      suppressed plasma viral load.

PMID- 20150183
TI  - Intrinsic sex differences in the early growth hormone responsiveness of sex
      specific genes in mouse liver.
AB  - Sex differences in liver gene expression are dictated by sex differences in
      circulating GH profiles. Presently, the pituitary hormone dependence of mouse
      liver gene expression was investigated on a global scale to discover sex-specific
      early GH response genes that could contribute to sex-specific regulation of
      downstream GH targets and to ascertain whether intrinsic sex differences
      characterize hepatic responses to plasma GH stimulation. Global RNA expression
      analysis identified two distinct classes of sex-specific mouse liver genes: genes
      subject to positive regulation (class I) and genes subject to negative regulation
      by pituitary hormones (class II). Genes activated or repressed in
      hypophysectomized (Hypox) mouse liver within 30-90 min of GH pulse treatment at a
      physiological dose were identified as putative direct targets of GH action (early
      response genes). Intrinsic sex differences in the GH responsiveness of a subset
      of these early response genes were observed. Notably, 45 male-specific genes,
      including five encoding transcriptional regulators that may mediate downstream
      sex-specific transcriptional responses, were induced by GH within 30 min in Hypox
      male but not Hypox female mouse liver. The early GH response genes were enriched
      in 29 male-specific targets of the transcription factor myocyte enhancer factor
      2, whose activation in hepatic stellate cells is associated with liver fibrosis
      leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid
      activation by GH pulses of certain sex-specific genes is modulated by intrinsic
      sex-specific factors, which may be associated with prior hormone exposure
      (epigenetic mechanisms) or genetic factors that are pituitary-independent, and
      could contribute to sex differences in predisposition to liver cancer or other
      hepatic patho-physiologies.

PMID- 20150184
TI  - Ligand-mediated activation of an engineered gs g protein-coupled receptor in
      osteoblasts increases trabecular bone formation.
AB  - Age-dependent changes in skeletal growth play important roles in regulating
      skeletal expansion and in the course of many diseases affecting bone. How G
      protein-coupled receptor (GPCR) signaling affects these changes is poorly
      understood. Previously, we described a mouse model expressing Rs1, an engineered
      receptor with constitutive G(s) activity. Rs1 expression in osteoblasts from
      gestation induced a dramatic age-dependent increase in trabecular bone with
      features resembling fibrous dysplasia; however, these changes were greatly
      minimized if Rs1 expression was delayed until after puberty. To further
      investigate whether ligand-induced activation of the G(s)-GPCR pathway affects
      bone formation in adult mice, we activated Rs1 in adult mice with the synthetic
      ligand RS67333 delivered continuously via an osmotic pump or intermittently by
      daily injections. We found that osteoblasts from adult animals can be stimulated
      to form large amounts of bone, indicating that adult mice are sensitive to the
      dramatic bone- forming actions of G(s) signaling in osteoblasts. In addition, our
      results show that intermittent and continuous activation of Rs1 led to
      structurally similar but quantitatively different degrees of trabecular bone
      formation. These results indicate that activation of a G(s)-coupled receptor in
      osteoblasts of adult animals by either intermittent or continuous ligand
      administration can increase trabecular bone formation. In addition, osteoblasts
      located at the bone epiphyses may be more responsive to G(s) signaling than
      osteoblasts at the bone diaphysis. This model provides a powerful tool for
      investigating the effects of ligand-activated G(s)-GPCR signaling on dynamic bone
      growth and remodeling.

PMID- 20150185
TI  - Mixed lineage kinase-3/JNK1 axis promotes migration of human gastric cancer cells
      following gastrin stimulation.
AB  - Gastrin is a gastrointestinal peptide hormone, secreted by the gastric G cells
      and can exist as a fully processed amidated form (G17) or as unprocessed forms.
      All forms of gastrin possess trophic properties towards the gastrointestinal
      mucosa. An understanding of the signaling pathways involved is important to
      design therapeutic approaches to target gastrin-mediated cellular events. The
      studies described here were designed to identify the signaling pathways by which
      amidated gastrin (G17) mediates cancer cell migration. These studies indicated a
      time- and dose-dependent increase in gastric cancer cell migration after G17
      stimulation, involving cholecystokinin 2 receptor. G17-induced migration was
      preceded by activation of MAPK pathways and was antagonized after pretreatment
      with SP600125, a pharmacological inhibitor of c-Jun-NH(2)-terminal kinase (JNK)
      pathway. Knockdown of endogenous JNK1 expression via small interference RNA (JNK1
      siRNA) inhibited G17-induced phosphorylation of c-Jun and migration, and
      overexpression of wild-type JNK1 or constitutive active JNK1 promoted G17-induced
      migration. Studies designed to identify the MAPK kinase kinase member mediating
      JNK activation indicated the involvement of mixed lineage kinase-3 (MLK3), which
      was transiently activated upon G17 treatment. Inhibition of MLK3 pathway via a
      pan-MLK inhibitor or knockdown of MLK3 expression by MLK3-siRNA antagonized G17
      induced migration. Incubation with G17 also resulted in an induction of matrix
      metalloproteinase 7 promoter activity, which is known to mediate migration and
      invasion pathways in cancer cells. Modulation of MLK3, JNK1, and c-Jun pathways
      modulated G17-induced matrix metalloproteinase 7 promoter activation. These
      studies indicate that the MLK3/JNK1 axis mediates G17-induced gastric cancer cell
      migration, which can be targeted for designing novel therapeutic strategies for
      treating gastric malignancies.

PMID- 20150186
TI  - Early hepatic insulin resistance in mice: a metabolomics analysis.
AB  - When fed with a high-fat safflower oil diet for 3 wk, wild-type mice develop
      hepatic insulin resistance, whereas mice lacking glycerol-3-phosphate
      acyltransferase-1 retain insulin sensitivity. We examined early changes in the
      development of insulin resistance via liver and plasma metabolome analyses that
      compared wild-type and glycerol-3-phosphate acyltransferase-deficient mice fed
      with either a low-fat or the safflower oil diet for 3 wk. We reasoned that diet
      induced changes in metabolites that occurred only in the wild-type mice would
      reflect those metabolites that were specifically related to hepatic insulin
      resistance. Of the identifiable metabolites (from 322 metabolites) in liver, wild
      type mice fed with the high-fat diet had increases in urea cycle intermediates,
      consistent with increased deamination of amino acids used for gluconeogenesis.
      Also increased were stearoylglycerol, gluconate, glucarate, 2-deoxyuridine, and
      pantothenate. Decreases were observed in S-adenosylhomocysteine, lactate, the
      bile acid taurocholate, and 1,5-anhydroglucitol, a previously identified marker
      of short-term glycemic control. Of the identifiable metabolites (from 258
      metabolites) in plasma, wild-type mice fed with the high-fat diet had increases
      in plasma stearate and two pyrimidine-related metabolites, whereas decreases were
      found in plasma bradykinin, alpha-ketoglutarate, taurocholate, and the tryptophan
      metabolite, kynurenine. This study identified metabolites previously not known to
      be associated with insulin resistance and points to the utility of metabolomics
      analysis in identifying unrecognized biochemical pathways that may be important
      in understanding the pathophysiology of diabetes.

PMID- 20150187
TI  - Achieving developmental synchrony in young children with hearing loss.
AB  - Children with hearing loss, with early and appropriate amplification and
      intervention, demonstrate gains in speech, language, and literacy skills. Despite
      these improvements many children continue to exhibit disturbances in cognitive,
      behavioral, and emotional control, self-regulation, and aspects of executive
      function. Given the complexity of developmental learning, educational settings
      should provide services that foster the growth of skills across multiple
      dimensions. Transdisciplinary intervention services that target the domains of
      language, communication, psychosocial functioning, motor, and cognitive
      development can promote academic and social success. Educational programs must
      provide children with access to the full range of basic skills necessary for
      academic and social achievement. In addition to an integrated curriculum that
      nurtures speech, language, and literacy development, innovations in the areas of
      auditory perception, social emotional learning, motor development, and vestibular
      function can enhance student outcomes. Through ongoing evaluation and
      modification, clearly articulated curricular approaches can serve as a model for
      early intervention and special education programs. The purpose of this article is
      to propose an intervention model that combines best practices from a variety of
      disciplines that affect developmental outcomes for young children with hearing
      loss, along with specific strategies and approaches that may help to promote
      optimal development across domains. Access to typically developing peers who
      model age-appropriate skills in language and behavior, small class sizes, a co
      teaching model, and a social constructivist perspective of teaching and learning,
      are among the key elements of the model.

PMID- 20150188
TI  - Application of paired-comparison methods to hearing AIDS.
AB  - The method of paired comparisons was introduced into the hearing aid literature
      nearly 50 years ago. Over time, studies have found paired comparisons to be
      sensitive, valid, and reliable in determining either the perceptual difference or
      relative ranking among hearing aids and electroacoustic characteristics. With the
      increasing number of adjustable electroacoustic parameters in today's digital
      hearing aids-and the lack of procedural guidelines necessary to fit many of them
      the method of paired comparisons provides the clinician with the ability to
      compare different devices, electroacoustic characteristics, memory settings, or
      combinations of these variables under the listener's everyday listening
      conditions. Furthermore, this procedure provides the clinician with the ability
      to individualize the prescriptive approach-which is predicated mainly on hearing
      threshold data and listening in quiet-so that a combination of parameters can be
      set to optimize the user's listening needs in a given environment. In this
      article, the authors present an overview of the theoretical principle supporting
      this procedure, the various paired-comparison strategies and associated
      approaches, the advantages of this method, and recommended procedures for
      implementing the method of paired comparisons in the fitting of today's
      sophisticated hearing aids.

PMID- 20150189
TI  - Short-term hearing aid benefit in a large group.
AB  - Short-term benefit in a very large group (N = 4,584) following hearing aid
      treatment was estimated using a revised version of the Self-Assessment of
      Communication (SAC-Hx). A total of 4,584 veterans with adult-onset hearing loss
      and mean audiometric findings consistent with a mild to severe, sloping,
      symmetrical, sensorineural hearing impairment were fitted with hearing aids.
      Responses to the SAC-Hx were gathered prior to and then 6 weeks following hearing
      aid fitting. Benefit was defined as the difference between the baseline and the
      posttreatment SAC-Hx scores. Hearing aid treatment resulted in robust and
      statistically significant benefit in each category of self-perceived
      communication consequences. Prior experience influenced benefit: New hearing aid
      users demonstrated the greatest magnitude of benefit, but even previously
      satisfied and dissatisfied users obtained significant benefit after new hearing
      aid fitting. Duration of experience did not have a remarkable effect on the
      magnitude of benefit: All groups with various durations of experience obtained
      comparable benefit. Severity of the baseline scores paralleled degree of hearing
      impairment when impairment was defined using a better ear pure tone average at
      1,000, 2,000, 3,000, and 4,000 Hz. Also, severity of perceived communication
      consequences paralleled poorer monosyllabic word recognition. Hearing aid
      treatment provided a functional, robust, and statistically significant benefit to
      individuals in all categories of hearing impairment (normal, mild, moderate,
      severe, and profound). This report demonstrates the feasibility of the SAC-Hx as
      a tool to efficiently assess outcome domains in hearing aid fitting.

PMID- 20150190
TI  - Recovery of severe neurological dysfunction after restoration of cerebral blood
      flow in acute aortic dissection.
AB  - Emergency repair has been successfully performed in acute type A aortic
      dissection complicated by cerebral malperfusion. Despite the lack of criteria to
      define irreversible brain damage, immediate surgery is often denied in case of
      stroke or coma. We report two patients presenting with coma and altered brainstem
      reflexes shortly after onset of aortic dissection, in whom aortic repair was
      successfully undertaken.

PMID- 20150191
TI  - Is skin closure with cyanoacrylate glue effective for the prevention of sternal
      wound infections?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed whether cyanoacrylate glue was effective at
      preventing wound infection following sternotomy incision. Altogether more than
      108 papers were found using the reported search, of which seven represented the
      best evidence to answer the clinical question. The authors, journal, date and
      country of publication, patient group studied, study type, relevant outcomes and
      results of these papers are tabulated. We conclude that applying cyanoacrylate
      glue to a sternal wound has superior outcomes in terms of infection rates, both
      if applied preoperatively (decreasing from 10.8% to 2.7% or 7.8% to 1.1%,
      according to two studies) and postoperatively (4.9%-2.1%). This trend is true of
      both deep surgical site infections (0.6%-0%) and superficial site infections
      (4.3%-2.1%). Furthermore, in patients who had developed mediastinitis following
      cardiac surgery rates of recurrent sternal detachment and osteomyelitis were
      significantly reduced in cases where sealant was applied compared to controls
      (35.3% vs. 0%). In all studies examining hospital stay, duration was reduced in
      cases where cyanoacrylate glue was used, both in patients treated for recurrent
      mediastinitis (24.06 vs. 14.16 days) and those with uncomplicated recovery
      following cardiac surgery (13 vs. 9 days). In addition, two studies examining the
      use of cyanoacrylate glue to secure the sternum in complicated cases of recurrent
      detachment report success rates of 86% and 100%.

PMID- 20150192
TI  - Higher hospital volume and specialisation.

PMID- 20150193
TI  - Relation between hospital orthopaedic specialisation and outcomes in patients
      aged 65 and older: retrospective analysis of US Medicare data.
AB  - OBJECTIVE: To explore the relation between hospital orthopaedic specialisation
      and postoperative outcomes after total hip or knee replacement surgery. DESIGN:
      Retrospective analysis of US Medicare data, 2001-5. SETTING: 3818 US hospitals
      carrying out total joint replacement. Population 1 273 081 Medicare beneficiaries
      age 65 and older who underwent primary or revision hip or knee replacement. MAIN
      OUTCOME MEASURES: Hospitals were stratified into fifths on the basis of their
      degree of orthopaedic specialisation (lowest fifth, least specialised; highest
      fifth, most specialised). The primary outcome was defined as a composite
      representing the occurrence of one or more of pulmonary embolism, deep vein
      thrombosis, haemorrhage, infection, myocardial infarction, or death within 90
      days of the index surgery. RESULTS: As hospital orthopaedic specialisation
      increased from the lowest fifth to highest fifth, the proportion of people
      admitted who were women or black, or who had diabetes or heart failure
      progressively decreased (P<0.001), whereas procedural volume increased. Compared
      with the most specialised hospitals (highest fifth), after adjustment for patient
      characteristics and hospital volume, the odds of adverse outcomes increased
      progressively with decreased hospital specialisation: lowest fifth (odds ratio
      1.59, 95% confidence interval 1.53 to 1.65), second fifth (1.32, 1.28 to 1.36),
      third fifth (1.24, 1.21 to 1.28), and fourth fifth (1.10, 1.07 to 1.13).
      CONCLUSIONS: Increased hospital orthopaedic specialisation is associated with
      improved patient outcomes after adjusting for both patient characteristics and
      hospital procedural volume. These results should be interpreted with caution
      because the possibility that other unmeasured confounders related to
      socioeconomic status or different factors are responsible for the improved
      patient outcomes rather than hospital specialisation can not be excluded. The
      findings suggest that hospital specialisation may capture different components of
      hospital quality than the components captured by hospital volume.

PMID- 20150194
TI  - Effect of reduced immunosuppression after kidney transplant failure on risk of
      cancer: population based retrospective cohort study.
AB  - OBJECTIVE: To compare cancer incidence in kidney transplant recipients during
      periods of transplant function (and immunosuppression) and after transplant
      failure (when immunosuppression is ceased or reduced). Design, setting, and
      participants Nationwide, population based retrospective cohort study of 8173
      Australian kidney transplant recipients registered on the Australia and New
      Zealand Dialysis and Transplant Registry who first received a transplant during
      1982-2003. Incident cancers were ascertained using linkage with national cancer
      registry records. MAIN OUTCOME MEASURES: Cancer-specific standardised incidence
      ratios for periods of transplant function and for dialysis after transplant
      failure. Incidence was compared between periods using multivariate incidence rate
      ratios adjusted for current age, sex, and duration of transplantation. RESULTS:
      All cases of Kaposi's sarcoma occurred during transplant function. Standardised
      incidence ratios were significantly elevated during transplant function, but not
      during dialysis after transplant failure, for non-Hodgkin's lymphoma, lip cancer,
      and melanoma. For each of these cancers, incidence was significantly lower during
      dialysis after transplant failure in multivariate analysis (incidence rate ratios
      0.20 (95% CI 0.06 to 0.65) for non-Hodgkin's lymphoma, 0.04 (0.01 to 0.31) for
      lip cancer, and 0.16 (0.04 to 0.64) for melanoma). In contrast, standardised
      incidence ratios during dialysis after transplant failure remained significantly
      elevated for leukaemia and lung cancer, and cancers related to end stage kidney
      disease (kidney, urinary tract, and thyroid cancers), with thyroid cancer
      incidence significantly higher during dialysis after transplant failure
      (incidence rate ratio 6.77 (2.64 to 17.39)). There was no significant difference
      in incidence by transplant function for other cancers. CONCLUSIONS: The effect of
      immunosuppression on cancer risk is rapidly reversible for some, but not all,
      cancer types. Risk reversal was mainly observed for cancers with a confirmed
      infectious cause. Risk of other cancers, especially those related to end stage
      kidney disease, remained significantly increased after reduction of
      immunosuppression.

PMID- 20150195
TI  - No quick fix for long term care.

PMID- 20150197
TI  - Flow cytometry and GISH reveal mixed ploidy populations and Spartina nonaploids
      with genomes of S. alterniflora and S. maritima origin.
AB  - BACKGROUND: The genus Spartina exhibits extensive hybridization and includes
      classic examples of recent speciation by allopolyploidy. In the UK there are two
      hexaploid species, S. maritima and S. alterniflora, as well as the homoploid
      hybrid S. x townsendii (2n = 60) and a derived allododecaploid S. anglica (2n =
      120, 122, 124); the latter two are considered to have originated in Hythe,
      southern England at the end of the 19th century. METHODS: Genomic in situ
      hybridization (GISH) and flow cytometry were used to characterize the genomic
      composition and distribution of these species and their ploidy levels at Eling
      Marchwood and Hythe, both near Southampton, southern England. KEY RESULTS: GISH
      identified approx. 60 chromosomes each of S. maritima and S. alterniflora origin
      in S. anglica and 62 chromosomes from S. alterniflora and 30 chromosomes from S.
      maritima in a nonaploid individual from Eling Marchwood, UK. GISH and flow
      cytometry also revealed that most (94 %) individuals examined at Hythe were
      hexaploid (the remaining two individuals (6 %) were dodedcaploid; n = 34),
      whereas hexaploid (approx. 36 % of plants), nonaploid (approx. 27 %) and
      dodecaploid (approx. 36 %) individuals were found at Eling Marchwood (n = 22).
      CONCLUSIONS: Nonaploid individuals indicate the potential for introgression
      between hexaploid and dodecaploid species, complicating the picture of polyploid
      induced speciation within the genus. Despite the aggressive ecological habit of
      S. anglica, it has not out-competed S. x townsendii at Hythe (homoploid hybrids
      at a frequency of 94 %, n = 34), despite >100 years of coexistence. The success
      of GISH opens up the potential for future studies of polyploid-induced genome
      restructuring in this genus.

PMID- 20150198
TI  - Localized application of soil organic matter shifts distribution of cluster roots
      of white lupin in the soil profile due to localized release of phosphorus.
AB  - BACKGROUND AND AIMS: Phosphorus (P) is a major factor controlling cluster-root
      formation. Cluster-root proliferation tends to concentrate in organic matter (OM)
      rich surface-soil layers, but the nature of this response of cluster-root
      formation to OM is not clear. Cluster-root proliferation in response to localized
      application of OM was characterized in Lupinus albus (white lupin) grown in
      stratified soil columns to test if the stimulating effect of OM on cluster-root
      formation was due to (a) P release from breakdown of OM; (b) a decrease in soil
      density; or (c) effects of micro-organisms other than releasing P from OM.
      METHODS: Lupin plants were grown in three-layer stratified soil columns where P
      was applied at 0 or 330 mg P kg(-1) to create a P-deficient or P-sufficient
      background, and OM, phytate mixed with OM, or perlite was applied to the top or
      middle layers with or without sterilization. KEY RESULTS: Non-sterile OM
      stimulated cluster-root proliferation and root length, and this effect became
      greater when phytate was supplied in the presence of OM. Both sterile OM and
      perlite significantly decreased cluster-root formation in the localized layers.
      The OM position did not change the proportion of total cluster roots to total
      roots in dry biomass among no-P treatments, but more cluster roots were
      concentrated in the OM layers with a decreased proportion in other places.
      CONCLUSIONS: Localized application of non-sterile OM or phytate plus OM
      stimulated cluster-root proliferation of L. albus in the localized layers. This
      effect is predominantly accounted for by P release from breakdown of OM or
      phytate, but not due to a change in soil density associated with OM. No evidence
      was found for effects of micro-organisms in OM other than those responsible for P
      release.

PMID- 20150199
TI  - Chronic fatigue syndrome.

PMID- 20150200
TI  - Factors influencing duration of exposure with symptoms and costs of occupational
      asthma.
AB  - The most important factor for the prognosis of occupational asthma is the length
      of exposure with symptoms prior to removal from exposure. We wanted to identify
      factors, including socioeconomic status, that can influence the delay in
      submitting a claim to a medicolegal agency after the onset of asthmatic symptoms,
      and to confirm that this delay is associated with worse respiratory prognosis and
      higher direct costs. This is a cross-sectional study of subjects who claimed
      compensation for occupational asthma at the Workers' Compensation Board of
      Quebec, Canada. Data were collected at re-evaluation ~2.5 yrs after diagnosis.
      Information on the number of years with symptoms and removal from exposure was
      obtained from the medicolegal file. 60 subjects were included in the study. Being
      older, having a revenue of >30,000 Canadian dollars and having occupational
      asthma due to high molecular weight agents were all positively associated with
      the number of years of exposure with symptoms before removal from exposure.
      Subjects with persistent airway hyperresponsiveness at follow-up had a higher
      number of years with symptoms. Experiencing symptoms in the workplace for <1 yr
      generated lower direct costs. These findings might help in surveillance
      programmes that could be preferentially targeted for these subgroups of workers.

PMID- 20150201
TI  - Socioeconomic risk factors for lung function decline in a general population.
AB  - The aim of our study was to examine sex-specific associations between different
      aspects of socioeconomic status (SES) (educational level, occupational status,
      income) and lung function in a general adult population. In the Hordaland County
      Cohort Study, 1,644 subjects aged 26-82 yrs at baseline answered questionnaires
      and performed post-bronchodilator spirometry both in 1996-1997 and in 2003-2006.
      We performed adjusted linear regression analysis on the effect of SES on decline
      in forced experimental volume in 1 s (FEV(1)), forced vital capacity (FVC) and
      FEV(1)/FVC. Mean annual decline in FEV(1) from baseline to follow-up was 57 mL
      (se 1.3) and 48 mL (se 1.0) for males and females, respectively. Males had a
      larger decline in FVC than females, while females had a larger decline in
      FEV(1)/FVC. Lower education and low occupational status were associated with
      larger male lung function decline. SES did not affect female lung function
      decline. However, marital status was a significant predictor; unmarried females
      had less decline than both married and widowed females in both FEV(1) (adjusted
      mean annual difference 8 mL and 16 mL) and FVC (adjusted mean annual difference 8
      mL and 18 mL). Low SES was associated with increased lung function decline in
      males. For females, marital status was more important.

PMID- 20150202
TI  - Influence of pneumococcal serotype group on outcome in adults with bacteraemic
      pneumonia.
AB  - The influence of infecting serotype group on outcome in bacteraemic pneumococcal
      pneumonia remains unclear. We performed a prospective, 10-yr observational study
      in an 800-bed teaching hospital. 299 adults diagnosed with pneumonia whose blood
      cultures showed growth of Streptococcus pneumoniae were included in the study.
      High invasive disease potential (H) serotypes included serotypes 1, 5 and 7F,
      which served as a reference category, were compared with low invasive disease
      potential (L) serotypes (3, 6A, 6B, 8, 19F, and 23F) and other (O) serotypes (non
      H, non-L). The influence on outcome was determined for each group of serotypes
      after adjusting for underlying conditions and severity of illness at admission.
      Overall, 30-day mortality was 11%. H serotypes (n = 93) infected primarily
      younger people and presented a higher risk of complicated parapneumonic effusion
      or empyema (17.2 versus 5.1%; p = 0.01), with lower mortality (3.2%). The
      isolation of L serotypes (n = 78) was an independent risk factor for 30-day
      mortality (OR 7.02, 95% CI 1.72-28.61), as were Charlson score (OR 1.30, 95% CI
      1.08-1.58), alcohol abuse (OR 3.99, 95% CI 1.39-11.39) and severity of illness
      measured by American Thoracic Society (ATS)/Infectious Diseases Society of
      America (IDSA) criteria (OR 4.80, 95% CI 1.89-12.13). A vaccination strategy
      including serotypes 3, 6A, 6B, 8, 19F and 23F may improve survival in adults.

PMID- 20150203
TI  - Application of a prediction model for work-related sensitisation in bakery
      workers.
AB  - Identification of work-related allergy, particularly work-related asthma, in a
      (nationwide) medical surveillance programme among bakery workers requires an
      effective and efficient strategy. Bakers at high risk of having work-related
      allergy were indentified by use of a questionnaire-based prediction model for
      work-related sensitisation. The questionnaire was applied among 5,325
      participating bakers. Sequential diagnostic investigations were performed only in
      those with an elevated risk. Performance of the model was evaluated in 674
      randomly selected bakers who participated in the medical surveillance programme
      and the validation study. Clinical investigations were evaluated in the first 73
      bakers referred at high risk. Overall 90% of bakers at risk of having asthma
      could be identified. Individuals at low risk showed 0.3-3.8% work-related
      respiratory symptoms, medication use or absenteeism. Predicting flour
      sensitisation by a simple questionnaire and score chart seems more effective at
      detecting work-related allergy than serology testing followed by clinical
      investigation in all immunoglobulin E class II-positive individuals. This
      prediction based stratification procedure appeared effective in detecting work
      related allergy among bakers and can accurately be used for periodic examination,
      especially in small enterprises where delivery of adequate care is difficult.
      This approach may contribute to cost reduction.

PMID- 20150204
TI  - Serotype-specific pneumococcal disease may be influenced by mannose-binding
      lectin deficiency.
AB  - Previous studies of the association between the mannose-binding lectin pathway
      deficiencies and invasive pneumococcal disease are inconclusive. Invasiveness of
      Streptococcus pneumoniae is dependent on serotype. We aimed to determine the
      association between invasive pneumococcal disease and MBL2 and MASP2 genetic
      variants, regarding serotype distribution. A hospital-based case-control study
      was conducted in children admitted to hospital in rural Mozambique in June 2002
      November 2003. The study included children admitted to hospital with invasive
      pneumococcal disease, in whom S. pneumoniae was isolated from blood and
      subsequently serotyped. Sequence-based typing analysis of amplicons covering the
      polymorphic regions of MASP2 (exon 3) and MBL2 (promoter and exon 1) was
      performed. An overall high frequency of MBL2 genotypes associated with low serum
      levels of MBL (43%) was found. Carriers of MBL-deficient genotypes were
      associated with invasive pneumococcal disease produced by low-invasive serotypes
      (OR 5.55, 95% CI 1.4-21.9; p = 0.01). Our data suggest that susceptibility to
      pneumococcal disease among MBL-deficient patients may be influenced by serotype
      invasiveness. Type-specific capsular serotype of S. pneumoniae would need to be
      taken into account in further genetic association studies of invasive
      pneumococcal disease.

PMID- 20150205
TI  - Reference equations for specific airway resistance in children: the Asthma UK
      initiative.
AB  - Plethysmographic specific airway resistance (sR(aw)) is a useful research method
      for discriminating lung disease in young children. Its use in clinical management
      has, however, been limited by lack of consensus regarding equipment, methodology
      and reference data. The aim of our study was to collate reference data from
      healthy children (3-10 yrs), document methodological differences, explore the
      impact of these differences and construct reference equations from the collated
      dataset. Centres were approached to contribute sR(aw) data as part of the Asthma
      UK initiative. A random selection of pressure-flow plots were assessed for
      quality and site visits elucidated data collection and analysis protocols. Five
      centres contributed 2,872 measurements. Marked variation in methodology and
      analysis excluded two centres. sR(aw) over-read sheets were developed for quality
      control. Reference equations and recommendations for recording and reporting both
      specific effective and total airway resistance (sR(eff) and sR(tot),
      respectively) were developed for White European children from 1,908 measurements
      made under similar conditions. Reference sR(aw) data collected from a single
      centre may be misleading, as methodological differences exist between centres.
      These preliminary reference equations can only be applied under similar
      measurement conditions. Given the potential clinical usefulness of sR(aw),
      particularly with respect to sR(eff), methodological guidelines need to be
      established and used in prospective data collection.

PMID- 20150206
TI  - Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by increased
      oxidative stress. Dietary factors, such as ample consumption of foods rich in
      antioxidants, such as fruit and vegetables, might have beneficial effects in COPD
      patients. The association between dietary shift to foods rich in antioxidants and
      lung function in COPD was investigated in a 3-yr prospective study. A total of
      120 COPD patients were randomised to follow either a diet based on increased
      consumption of fresh fruit and vegetables (intervention group (IG)) or a free
      diet (control group (CG)). The mean consumption of foods containing antioxidants
      was higher in the IG than in the CG throughout the study period (p<0.05). The
      relationship between consumption of foods rich in antioxidants and percentage
      predicted forced expiratory volume in 1 s was assessed using a general linear
      model for repeated measures; the two groups overall were different in time (p =
      0.03), with the IG showing a better outcome. In investigating the effect of
      several confounders (sex, age, smoking status, comorbid conditions and
      exacerbation) of group response over time, nonsignificant interactions were found
      between confounders, group and time. These findings suggest that a dietary shift
      to higher-antioxidant food intake may be associated with improvement in lung
      function, and, in this respect, dietary interventions might be considered in COPD
      management.

PMID- 20150207
TI  - Azithromycin induces anti-viral responses in bronchial epithelial cells.
AB  - The majority of asthma exacerbations are caused by rhinovirus. Currently the
      treatment of asthma exacerbations is inadequate. Previous evidence suggests that
      macrolide antibiotics have anti-inflammatory and antiviral effects; however, the
      mechanism is unknown. We investigated the anti-rhinoviral potential of macrolides
      through the induction of antiviral gene mRNA and protein. Primary human bronchial
      epithelial cells were pre-treated with the macrolides azithromycin, erythromycin
      and telithromycin, and infected with minor-group rhinovirus 1B and major-group
      rhinovirus 16. The mRNA expression of the antiviral genes, type I interferon-beta
      and type III interferon-lambda1, interferon-lambda2/3, and interferon-stimulated
      genes (retinoic acid inducible gene I, melanoma differentiation associated gene
      5, oligoadenylate synthase, MxA and viperin) and pro-inflammatory cytokines
      (interleukin (IL)-6 and IL-8), and rhinovirus replication and release were
      measured. Azithromycin, but not erythromycin or telithromycin, significantly
      increased rhinovirus 1B- and rhinovirus 16-induced interferons and interferon
      stimulated gene mRNA expression and protein production. Furthermore, azithromycin
      significantly reduced rhinovirus replication and release. Rhinovirus induced IL-6
      and IL-8 protein and mRNA expression were not significantly reduced by
      azithromycin pre-treatment. In conclusion, the results demonstrate that
      azithromycin has anti-rhinoviral activity in bronchial epithelial cells and,
      during rhinovirus infection, increases the production of interferon-stimulated
      genes.

PMID- 20150208
TI  - Cigarette smoke enhances {beta}-defensin 2 expression in rat airways via nuclear
      factor-{kappa}B activation.
AB  - beta-defensin 2 (BD-2), an antimicrobial peptide, participates in airway defence.
      Cigarette smoke (CS) is a major risk factor for the development of chronic
      obstructive pulmonary disease. This study mainly aims to investigate the effect
      of CS on rat BD-2 (rBD-2) expression in rat airways. Rats were exposed to CS and
      treated with caffeic acid phenethyl ester (CAPE), a nuclear factor (NF)-kappaB
      inhibitor, or astragaloside IV (AS-IV), an active ingredient of Astragalus
      mongholicus. Besides the analysis of bronchoalveolar lavage fluid (BALF) and
      histological changes after CS exposure, rBD-2 expression was investigated with
      immunohistochemistry, reverse transcription PCR and ELISA. Total glutathione and
      nitric oxide (NO) levels in rat lungs were also detected. CS exposure markedly
      increased rBD-2 immunoreactivity, as well as rBD-2 mRNA and protein levels in rat
      airways, which were inhibited by CAPE treatment. Moreover, associated airway
      inflammation induced by CS was demonstrated by histological changes, increased
      cell counts and pro-inflammatory cytokines in BALF, and NF-kappaB activation and
      high levels of total glutathione and NO, which were all reversed by AS-IV in a
      dose-dependent fashion. In conclusion, CS exposure induces rBD-2 expression in
      rat airways via a NF-kappaB-dependent pathway, and AS-IV attenuates CS-induced
      airway inflammation due to its anti-inflammatory and antioxidant properties, at
      least partly through NF-kappaB inactivation.

PMID- 20150209
TI  - Intraoperative vital and haemodynamic monitoring using an integrated multiple
      channel monitor in rats.
AB  - The aim of this study is to give a hands-on description of the successful
      monitoring procedure established for extended liver resections and liver
      transplantations in rats and to provide the typical range of data as obtained
      before and after a hepatobiliary surgical procedure (right median hepatic vein
      [RMHV] ligation) in healthy male Lewis rats. All manipulations were performed in
      anaesthetized (3% isoflurane in O(2) 1 L/min) healthy male Lewis rats (250-350 g)
      with an integrated multiple-channel intraoperative monitor (Powerlab system)
      using a series of sensors for data acquisition. Vital parameters (body
      temperature, electrocardiogram, respiratory rate and heart rate), haemodynamic
      parameters (mean arterial blood pressure [MAP] and central venous pressure) and
      liver perfusion parameters (inferior hepatic venous pressure, portal vein
      pressure [PVP], blood flow of portal vein and inferior hepatic cava) were
      monitored. Catheters were placed in microsurgical technique after careful
      exposure guided by anatomical landmarks. Vascular incisions were closed with
      interrupted sutures. Complete instrumentation of animals was performed within 1
      h. No specific complications occurred. Vital and haemodynamic parameters such as
      MAP (94 +/- 16.2 mmHg) or portal pressure (9.6 +/- 1.34 mmHg) were in the same
      range as known for humans (MAP = 100 mmHg, portal pressure = 5-10 mmHg), whereas
      parameters dependent on the size of the body or organ such as flow rates (portal
      blood flow = 16.2 +/- 6 mL/min) were obviously different compared with those of
      humans (portal blood flow = 800 mL/min). In conclusion, the normal range for
      vital, haemodynamic and liver perfusion parameters was reported as reference
      values to allow quality control for future surgical hepatobiliary research
      projects. As the procedure can be easily learned, the extensive intraoperative
      monitoring can be used routinely.

PMID- 20150210
TI  - Identifying the "tipping point" age for overweight pediatric patients.
AB  - According to the National Health and Nutrition Examination Survey in 2007, nearly
      half of all American children are either overweight or obese. Retrospective chart
      review identified patients with the diagnostic codes for overweight, obese,
      and/or excessive weight gain. Inclusion criteria were current age between 2 and
      20 years, a minimum of 5 visits with weight and height measurements, and a body
      mass index (BMI) at or above the 85th percentile. A total of 184 patients met
      inclusion criteria. More than half the children became overweight before age 2,
      and all patients were obese or overweight by age 10. The rate of gain is
      approximately 1 excess BMI unit/year, therefore causing most children to be
      overweight by age 2 (R (2) = .53). This study indicates that the critical period
      for preventing childhood obesity in this subset of identified patients is during
      the first 2 years of life and for many by 3 months of age.

PMID- 20150211
TI  - Barriers to pediatric lead screening: implications from a web-based survey of
      Vermont pediatricians.
AB  - The pernicious effects of lead on child health are well documented. The Vermont
      Department of Health (VDH) recommends screening all 12- and 24-month-old children
      for elevated blood lead levels (BLL). In 2006, only 41.4% of 24-month-old Vermont
      children were screened. To identify barriers preventing pediatricians from
      performing blood lead screening, a survey was distributed to Vermont primary care
      pediatricians-divided in higher and lower screening groups. Vermont pediatricians
      were more likely to be lower screeners if they reported negative health outcomes
      began at BLL >" xbd="641" xhg="618" ybd="1456" yhg="1421"/> 10 microg/dL (odds
      ratio [OR] = 3.64, 95% confidence interval [CI] = 1.12-11.99), practiced in
      Chittenden County (OR = 3.34, 95% CI = 1.14-9.78), or disagreed with the VDH's
      recommendation (OR = 4.90, 95% CI = 1.66-15.50). Adjusted analysis indicated the
      most significant determinants of lower screening rates were male gender, a
      perceived dangerous BLL as >10 microg/dL and low self-reported Medicaid
      population. The VDH may have an opportunity to increase BLL screening emphasizing
      the significant health risks associated with BLL < or = 10 microg/dL.

PMID- 20150212
TI  - Increasing incidence of community-associated atypical Clostridium difficile
      disease in children.
AB  - Forty-one children with a variety of gastrointestinal complaints were diagnosed
      with Clostridium difficile infections as part of a routine screen over 3 years.
      The infection had not been suspected prior to the screen. Each child responded to
      treatment with metronidazole with resolution of their symptoms. These data
      suggest that community-associated C difficile is increasing and may produce
      atypical disease and lead to misdiagnosis.

PMID- 20150213
TI  - Urinary proteases degrade albumin: implications for measurement of albuminuria in
      stored samples.
AB  - BACKGROUND: Previous studies have shown that albumin in stored urine samples
      degrades over time, and that albumin losses are greatest in samples with low pH
      conditions (pH < 5). Furthermore, the high-performance liquid chromatography
      (HPLC) assay for urinary albumin has been shown to be particularly susceptible to
      the effects of prolonged storage. METHODS: Frozen urine samples, stored for 12
      months at -70 and -20 degrees C, were analysed for albumin fragmentation. Urinary
      protease activity was investigated in vitro in urine adjusted to pH 2.3-2.5.
      Albumin was measured by nephelometry, HPLC and sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. RESULTS: In the unadjusted samples, albumin
      was degraded in 11 out of 40 samples stored at -20 degrees C. In the in vitro
      experiments, both endogenous albumin and exogenous albumin added to urine were
      rapidly degraded into large fragments within minutes after adjustment to low pH.
      The fragments produced were consistent with those produced during digestion with
      pepsin and urinary degradation was completely inhibited by pepstatin. Albumin
      concentration measured by HPLC was most dramatically affected, with near-complete
      loss of albumin-sized material within one hour of incubation at pH 2.3-2.5.
      Sample reactivity with antiserum in a nephelometry assay initially declined then
      increased, possibly due to exposure of internal epitopes during albumin
      digestion. CONCLUSIONS: This study demonstrated that proteases are present and
      active in stored human urine samples. Urinary albumin digestion occurred in a
      manner consistent with activity of endogenous urinary proteases. Adjustment to
      neutral pH or addition of protease inhibitors may be useful techniques for sample
      preservation.

PMID- 20150214
TI  - A simplified liquid chromatography tandem mass spectrometry assay, using on-line
      solid-phase extraction, for the quantitation of cortisol in saliva and comparison
      with a routine DELFIA method.
AB  - BACKGROUND: We have developed a liquid chromatography tandem mass spectrometry
      (LC-MS/MS) method for measuring salivary cortisol, which requires only 200 microL
      sample and no extraction. METHODS: Sample (200 microL) and 25 microL internal
      standard were added directly to a 96-deep-well plate. Of this, 50 microL was
      loaded onto a guard cartridge, the cartridge was then washed and the eluate was
      diverted to waste. The compounds were eluted from the guard cartridge onto the
      C18 analytical column. Cortisol and deuterated cortisol were monitored using
      transitions m/z 363.2 > 121.1 and 365.1 > 122.2, respectively. RESULTS: The
      method had a lower limit of quantitation of 2 nmol/L. Intra-assay and inter-assay
      imprecision were better than 9.5%. Comparison with an established dissociation
      enhanced lanthanide fluorescent immunoassay (DELFIA) gave good agreement for the
      majority of samples; LC-MS/MS = 1.0065 x DELFIA - 3.7 (n = 130). The reference
      range was determined to be 5.8-45.7 nmol/L at 08:00 h and <6.4 nmol/L at 23:00 h
      (n = 44). CONCLUSIONS: We have developed a simple, robust assay to measure
      salivary cortisol using on-line solid-phase extraction to reduce sample clean-up
      requirements.

PMID- 20150215
TI  - National UK audit of the short synacthen test.
AB  - We present the first national audit of the Short Synacthen Test (SST),
      identifying the clinical, analytical and interpretative procedures adopted by 89
      laboratories. BACKGROUND: The SST has replaced the insulin stress test as the
      first-line test to assess adrenal insufficiency and has received considerable
      attention regarding its sensitivity and specificity. Concerns regarding this test
      include the bias of cortisol methods, cut-off values used, contraindications and
      the limitations of the test in diagnosing recent, mild secondary adrenal
      insufficiency. The audit took into consideration the protocols used by
      laboratories, the advice provided prior and after the SST and the analytical bias
      of the methods used. METHODS: A web-based questionnaire using Microsoft
      FrontPage(TM) was prepared to collect data from laboratories and provided drop
      down lists and other form-field elements to capture additional comments. The
      resultant data were exported to Microsoft Excel(TM) for data clean-up and
      analysis. RESULTS: The workloads were highly variable; however, most laboratories
      were in general agreement to the indications, contraindications, timing and
      reference ranges. In contrast, there was variability in the bias of the cortisol
      methods, which had not been translated to the cut-off values used by the majority
      of laboratories. CONCLUSIONS: The audit has shown that though the preanalytical
      procedures were similar in most laboratories, there is a requirement to recognize
      the effect that method bias may have on the reference ranges and consequently on
      the diagnosis of adrenal insufficiency. There is a need to develop consensus
      guidelines, which can aid both clinicians and laboratories.

PMID- 20150216
TI  - Investigation of a problem with external quality assurance samples for faecal
      occult blood.
AB  - BACKGROUND: It is vital that laboratories participate in External Quality
      Assurance (EQA) programmes, but results from such schemes do not necessarily help
      ensure assays are 'in control'. We describe a series of experiments undertaken to
      explore apparent poor performance in an occult blood EQA scheme that manifested
      as a series of false-negatives. As a consequence of our laboratory misclassifying
      some EQA samples, we decided to design a simple sensitivity study that would
      reaffirm confidence in our testing procedures. METHODS: In order to verify
      analyst reliability and analytical sensitivity, a series of 10 faecal samples
      were supplemented with increasing amounts of whole blood (0-1.0 mg/Hb/g faeces)
      and these were then tested independently by four different operatives. EQA
      samples which our laboratory misclassified were shared with and tested by a
      second laboratory and results compared. RESULTS: The results demonstrated
      consistency in interpretation among the four 'testers' and also suggested that
      the sensitivity of the method is 0.7 rather than 0.6 mg/Hb/g faeces as claimed by
      the manufacturer. The second laboratory obtained identical results as our
      laboratory for the EQA samples which our laboratory had misclassified.
      CONCLUSIONS: Occult blood EQA scheme results might not give a true reflection of
      a laboratory's ability to provide reliable results. We would encourage any
      laboratory observing relative poor performance to undertake local sensitivity
      studies and repeat testing of EQA samples if in any doubt.

PMID- 20150217
TI  - Quantitative mass spectrometry of histones H3.2 and H3.3 in Suz12-deficient mouse
      embryonic stem cells reveals distinct, dynamic post-translational modifications
      at Lys-27 and Lys-36.
AB  - SUZ12 is a core component of the polycomb repressive complex 2 (PRC2) and is
      required for the differentiation of mouse embryonic stem cells (ESCs). PRC2 is
      associated with transcriptional repression via methylation of H3 Lys-27. We
      applied quantitative mass spectrometry to investigate the effects of Suz12
      deficiency on H3.2 and H3.3 from mouse ESCs. Using high mass accuracy MS combined
      with CID or electron transfer dissociation (ETD) tandem mass spectrometry, we
      identified a total of 81 unique modified peptides from H3.2 and H3.3 and assigned
      46 modifications at 22 different positions, including distinct coexisting
      modifications. In certain cases, high mass accuracy LTQ-Orbitrap MS/MS allowed
      precise localization of near isobaric coexisting PTMs such as trimethylation and
      acetylation within individual peptides. ETD MS/MS facilitated sequencing and
      annotation of phosphorylated histone peptides. The combined use of ETD and CID
      MS/MS increased the total number of identified modified peptides. Comparative
      quantitative analysis of histones from wild type and Suz12-deficient ESCs using
      stable isotope labeling with amino acids in cell culture and LC-MS/MS revealed a
      dramatic reduction of H3K27me2 and H3K27me3 and an increase of H3K27ac, thereby
      uncovering an antagonistic methyl/acetyl switch at H3K27. The reduction in H3K27
      methylation and increase in H3K27 acetylation was accompanied by H3K36
      acetylation and methylation. Estimation of the global isoform percentage of
      unmodified and modified histone peptides (amino acids 27-40) showed the relative
      distribution of distinct coexisting histone marks. Our study revealed limitations
      of antibody-based Western blotting methods for detection of coexisting protein
      modifications and demonstrated the utility of quantitative tandem mass
      spectrometry for detailed analysis of the dynamics of coexisting post
      translational modifications in proteins.

PMID- 20150218
TI  - The reproduction number of seasonal influenza epidemics in Brazil, 1996-2006.
AB  - The transmission dynamics of influenza in tropical regions are poorly understood.
      Here we explore geographical variations in the reproduction number of influenza
      across equatorial, tropical and subtropical areas of Brazil, based on the
      analysis of weekly pneumonia and influenza (P&I) mortality time series in 27
      states. The reproduction number (R) was low on average in Brazil (mean = 1.03
      (95% CI 1.02-1.04), assuming a serial interval of 3 days). Estimates of the
      reproduction number were slightly lower for Brazil than for the USA or France
      (difference in mean R = 0.08, p < 0.01) and displayed less between-year variation
      (p < 0.001). Our findings suggest a weak gradient in the reproduction number with
      population size, where R increases from low population in the North to high
      population in the South of Brazil. Our low estimates of the reproduction number
      suggest that influenza population immunity could be high on average in Brazil,
      potentially resulting in increased viral genetic diversity and rate of emergence
      of new variants. Additional epidemiological and genetic studies are warranted to
      further characterize the dynamics of influenza in the tropics and refine our
      understanding of the global circulation of influenza viruses.

PMID- 20150219
TI  - A mineral-rich red algae extract inhibits polyp formation and inflammation in the
      gastrointestinal tract of mice on a high-fat diet.
AB  - The purpose of this study was to determine whether a mineral-rich extract derived
      from the red marine algae Lithothamnion calcareum could be used as a dietary
      supplement for chemoprevention against colon polyp formation. A total of 60
      C57bl/6 mice were divided into 3 groups based on diet. One group received a low
      fat, rodent chow diet (AIN76A). The second group received a high-fat "Western
      style" diet (HFWD). The third group was fed the same HFWD with the mineral-rich
      extract included as a dietary supplement. Mice were maintained on the respective
      diets for 15 months. Autopsies were performed at the time of death or at the
      completion of the study. To summarize, the cumulative mortality rate was higher
      in mice on the HFWD during the 15-month period (55%) than in mice from the low
      fat diet or the extract-supplemented high-fat diet groups (20% and 30%,
      respectively; P < .05 with respect to both). Autopsies revealed colon polyps in
      20% of the animals on the HFWD and none in animals of the other 2 groups (P <
      .05). In addition to the grossly visible polyps, areas of hyperplasia in the
      colonic mucosa and inflammatory foci throughout the gastrointestinal tract were
      observed histologically in animals on the high-fat diet. Both were significantly
      reduced in animals on the low-fat diet and animals on the extract-supplemented
      HFWD.These data suggest that the mineral-rich algae extract may provide a novel
      approach to chemoprevention in the colon.

PMID- 20150220
TI  - A phase II study of an herbal decoction that includes Astragali radix for cancer
      associated anorexia in patients with advanced cancer.
AB  - HYPOTHESIS: Anorexia and cancer cachexia produce significant loss of adipose
      tissue and muscle mass and eventually reduce survival in cancer patients. STUDY
      DESIGN: This phase II study was conducted to assess the efficacy and the safety
      of an herbal decoction with Astragali radix in patients with anorexia in advanced
      cancer. METHODS: All patients with histologic evidence of an incurable malignancy
      had a weight loss of at least 5% during the preceding 6 months and a patient
      estimated severe anorexia.The herbal decoction was administered 30 minutes after
      meals, three times a day for 3 weeks.The score of appetite, body weight, the
      cytokines, IL-1beta, IL-6, TNF-alpha, and anthropometric measurements were
      assessed. For the assessment of anorexia, a visual analog scale (VAS: 0 mm = no
      anorexia, 100 mm = maximal anorexia) was used. RESULTS: Eleven patients were
      recruited from January, 2007 to January, 2009. The mean age was 59.8 years old.
      The change in anorexia from baseline with the herbal decoction was significantly
      different and anorexia was improved (anorexia VAS score, 60 mm vs. 40 mm, p =
      0.008). The mean value of the maximal body weight was 55.6 kg and differed
      significantly from the 54.6 kg at baseline (p = 0.009). Changes in cytokine
      levels and anthropometric measurements from baseline to the 3rd week were not
      significant. All toxicities were manageable. CONCLUSION: Appetite and body weight
      were improved with the herbal decoction. This herbal decoction shows some
      potential for management of cancer-related anorexia.

PMID- 20150221
TI  - Curcuma wenyujin extract induces apoptosis and inhibits proliferation of human
      cervical cancer cells in vitro and in vivo.
AB  - An essential oil extract, derived from the rhizome of Curcuma wenyujin (CWE),
      possesses antioxidative, antimicrobial, and anti-inflammatory properties.
      However, it remains unknown how exactly CWE inhibits tumor growth. In this study,
      using human cervical cancer HeLa cells, the authors postulated that CWE has the
      ability to inhibit tumor growth. The study shows that CWE dose-dependently
      suppressed colony formation and inhibited the proliferation of HeLa cells through
      blockade of cell cycle progression at G1 phase and apoptosis. CWE-induced G1
      arrest was associated with retinoblastoma protein dephosphorylation and reduced
      amounts of cyclins D1 and D3, and cyclin-dependent kinase 4 and 6 proteins. CWE
      treatment resulted in apoptosis in HeLa cells as evidenced by morphological
      changes, caspase activation and PARP cleavage, which can be reversed by a pan
      caspase inhibitor. It was observed that CWE treatment activated the mitochondrial
      apoptotic pathway indicated by a decrease in Mcl-1 and Bcl-xL levels, resulting
      in mitochondrial membrane potential loss and caspases 9 activation. CWE-treated
      cells displayed reduced PTEN, AKT, and STAT3 phosphorylation and downregulation
      of NFkappaB signaling, providing a mechanism for the G1 arrest and apoptosis
      observed. Furthermore, CWE inhibited tumor growth of HeLa in a xenograft mouse
      tumor model, suggesting that CWE inhibited tumorigenesis by inhibiting cell
      proliferation and inducing apoptosis. These findings are the first to reveal the
      molecular basis for the anticervical cancer action of CWE. The results suggest
      that CWE could be developed as a drug for the management of cervical cancer.

PMID- 20150222
TI  - Relative biological effectiveness and cell-killing efficacy of continuous low
      dose-rate 125I seeds on prostate carcinoma cells in vitro.
AB  - The aim of this study was to determine the effects of (125)I seeds on prostate
      carcinoma (PC3) cells. The relative biological effectiveness of (125)I seeds on
      PC3 cells with respect to (60)Co gamma rays was 1.4. Both 4 Gy of (60)Co gamma
      ray and (125)I seed irradiation increased the percentage of cells in G(2) phase,
      but there was no significant difference between these 2 types of radiation.
      Significantly, (125)I seeds induced higher apoptotic rates of PC3 cells compared
      with (60)Co gamma ray irradiation. Furthermore, Bcl-2 expression, but not caspase
      3 activity, in PC3 cells was downregulated after irradiation with (125)I seed or
      (60)Co gamma rays.

PMID- 20150223
TI  - Therapeutic effects of HESA-A in patients with end-stage metastatic cancers.
AB  - BACKGROUND: After cardiovascular disease, cancer is the most common cause of
      death. HESA-A is a natural product of herbal and marine origin. The aim of this
      study was to investigate the beneficial effects of HESA-A in patients with end
      stage metastatic cancers. METHODS: In this clinical trial, 30 consecutive
      patients (18 men, 12 women) with end-stage cancers and liver metastasis at the
      Cancer Research Center of Tehran University of Medical Sciences were studied.
      Patients received HESA-A 50 mg/kg/d orally in 2 to 3 divided doses for 3 months.
      At the start and end of the 1st, 4th, 8th, and 12th weeks of the study, the
      patients were assessed and hematological and hepatic biochemical indices were
      measured. Also, the Karnofsky Performance Scale questionnaire was completed for
      each patient. RESULTS: The mean age of patients was 56.23 +/- 12.10 years. Mean
      Karnofsky Performance Scale scores of the patients increased from 48 +/- 14.36 to
      78.42 +/- 15.37 after 12 weeks of treatment. A total of 90.4% of the patients who
      remained in the study were alive for 12 weeks. No significant hepatic or
      hematologic adverse effect was seen during the study. CONCLUSION: HESA-A appears
      to be an effective and safe anticancer compound that may increase survival of end
      stage patients and can be used in selected cases. Further prospective controlled
      clinical trials with large sample size and longer follow-up period are warranted
      to understand the mechanisms of action of HESA-A and evaluate its long-term
      effects on the survival and quality of life of patients with cancer and as well
      as its unfavorable side effects.

PMID- 20150224
TI  - Apoptotic effects of Physalis minima L. chloroform extract in human breast
      carcinoma T-47D cells mediated by c-myc-, p53-, and caspase-3-dependent pathways.
AB  - The chloroform extract of Physalis minima produced a significant growth
      inhibition against human T-47D breast carcinoma cells as compared with other
      extracts with an EC(50) value of 3.8 microg/mL. An analysis of cell death
      mechanisms indicated that the extract elicited an apoptotic cell death. mRNA
      expression analysis revealed the coregulation of apoptotic genes, that is, c-myc
      , p53, and caspase-3. The c-myc was significantly induced by the chloroform
      extract at the earlier phase of treatment, followed by p53 and caspase-3.
      Biochemical assay and ultrastructural observation displayed typical apoptotic
      features in the treated cells, including DNA fragmentation, blebbing and
      convolution of cell membrane, clumping and margination of chromatin, and
      production of membrane-bound apoptotic bodies. The presence of different stages
      of apoptotic cell death and phosphatidylserine externalization were further
      reconfirmed by annexin V and propidium iodide staining. Thus, the results from
      this study strongly suggest that the chloroform extract of P. minima induced
      apoptotic cell death via p53-, caspase-3-, and c-myc-dependent pathways.

PMID- 20150226
TI  - Integrative oncology for the whole person: a multidimensional approach to cancer
      care.
AB  - Today, more than ever before, millions of people are seeking an approach to
      medicine and health care that is more comprehensive, more holistic and
      integrative, and more compassionate and sensitive to their needs as a whole
      person. This is particularly true for those dealing with cancer. Changing patient
      demographics, heightened consumer demand for complementary and alternative
      medicine (CAM) products and services, advances in medical science and technology,
      expanding access to the Internet and health information, and other factors have
      contributed to a wave of transformation that is unprecedented in its impact on
      the entire health care system. These trends have fueled the emerging fields of
      integrative medicine and oncology, which are growing rapidly. As these fields
      continue to evolve, they will move beyond the present integrative model to a
      broader vision of whole-person, multidimensional care that will more fully and
      coherently address and embrace all dimensions of the human experience. This
      article describes 6 major driving forces behind the wave of transformation
      presently under way in medicine and health care. It provides a brief, historical
      overview of integrative medicine and oncology and summarizes the present status
      of these emerging fields. It discusses the future of integrative medicine and
      oncology, including a multidimensional approach to care, and highlights 5 key
      elements that underlie this approach. Finally, it describes The Seven Levels of
      Healing--a model of multidimensional care--and concludes with a discussion of 3
      important challenges and opportunities for medicine and health care that lie on
      the horizon.

PMID- 20150225
TI  - Tocotrienols inhibited growth and induced apoptosis in human HeLa cells through
      the cell cycle signaling pathway.
AB  - Tocotrienols of palm oil have been shown to possess potent neuroprotective,
      antioxidative, anticancer, and cholesterol-lowering activities. In this study,
      the authors examined the antiproliferative effects of alpha-, gamma- and delta
      tocotrienols (alphaT3, gammaT3, and deltaT3), and alpha-tocopherol (alphaT) in
      human cervical carcinoma (HeLa) cells. Their mechanism(s) of action on cell cycle
      signaling pathway were also investigated. RESULTS: 3.19 +/- 0.05 microM) and
      gammaT3 (IC(50): 2.85 +/- 0.07 microM) was more potent than deltaT3 (IC(50): >100
      microM) and alphaT (IC(50): 69.46 +/- 3.01 microM). Both alphaT3 and gammaT3 also
      demonstrated a dose-dependent and time-dependent induction of cell death.They
      caused cell cycle arrest at G2/M phase and triggered apoptosis as displayed by
      the externalization of annexin V-targeted phosphatidylserine and accumulation of
      sub-G1 peak. At a concentration of 3 microM, alphaT3 downregulated the expression
      of cyclin D3, p16, and CDK6, while having no effect on cyclin D1, p15, p21, p27,
      and CDK4 expression. However, gammaT3 showed no effect on these proteins. The
      induction of HeLa cell apoptosis by alphaT3 and gammaT3 appeared to be associated
      with the expression of IL-6, but not the other cytokines (IFN-gamma, IL-2, and IL
      10).Taken together, the results suggest that alphaT3 and gammaT3 are more
      effective than deltaT3 and alphaT in inhibiting HeLa cell proliferation, and
      their mode of action could be through the upregulation of IL-6, and the
      downregulation of cyclin D3, p16, and CDK6 expression in the cell cycle signaling
      pathway.

PMID- 20150227
TI  - Pain following 980-nm endovenous laser ablation and segmental radiofrequency
      ablation for varicose veins: a prospective observational study.
AB  - OBJECTIVES: The aim of this study was to evaluate postoperative pain following
      endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) and identify
      risk factors for increased pain. METHODS: Patients undergoing either segmental
      RFA (VNUS Closure Fast, VNUS Medical Technologies, San Jose, California) or EVLA
      (980 nm) for varicose veins completed a preoperative disease-specific quality-of
      life questionnaire (Aberdeen Varicose Vein Questionnaire [AVVQ]) and a diary card
      recording postoperative pain, return to normal activities, and return to work.
      Median 3- and 10-day pain scores were calculated. RESULTS: In all, 81 patients
      returned diary cards (RFA = 45, EVLA = 36). Patients receiving RFA reported less
      postoperative pain than those receiving EVLA at 3 days (14.5 vs 25.8 mm, P =
      .053, Mann-Whitney U test) and 10 days (13 vs 23.3 mm, P = .014, Mann-Whitney U
      test) and returned to work earlier than those receiving EVLA (median 5 vs 9 days,
      P = .022). CONCLUSIONS: Patients treated with segmental RFA had less
      postoperative pain and returned to work quicker than those treated with EVLA.

PMID- 20150228
TI  - Hemocompatibility of carotid artery stents: alterations of the electrical
      parameters of erythrocyte cell membrane--a word of caution.
AB  - The hemocompatibility of standard surgical treatment of carotid artery disease
      through the insertion of metallic stents is investigated by means of radio wave
      dielectric spectroscopy technique that allows the measurements of the electrical
      parameters of the red blood cell membrane. Our measurements suggest that both the
      membrane permittivity and the membrane conductivity, which characterize the
      overall electrical behavior of the cell membrane, undergo an appreciable
      alteration of their standard values as a consequence of the stent insertion.
      These alterations persist over long period of time, up to 4 weeks. Even if these
      effects could not cause any evident damage at physiological or clinical level to
      the patient, the presence of a host response to the stent implant suggests that a
      full hemocompatibility has not yet reached, and a word of caution is necessary.

PMID- 20150229
TI  - Wake-up test decrease shunts insertion during carotid endarterectomy under
      general anesthesia.
AB  - OBJECTIVE: The use of locoregional anesthesia versus general anesthesia (GE) in
      carotid endarterectomy (CEA) has been a debatable issue in clinical studies for
      the past several years. In our study, GE with wake-up tests (WUTs) during carotid
      cross-clamping was used instead of stump pressure (SP) to directly assess the
      neurological status of the patient to determine whether shunting was needed. Our
      study assessed the percentage of patients under light sedation and mechanically
      ventilated needing shunting based on WUT compared to a systolic stump pressure
      (SPs) cutoff value of <or=40 mm Hg. DESIGN: Retrospective, observational study.
      SETTING: University hospital clinic. PARTICIPANTS: Three hundred fifty-one
      patients (American Society of Anesthesiologists physical class II-III) with
      carotid artery stenosis scheduled for CEA under GE. INTERVENTIONS: The WUT was
      used to assess the neurological status in patients undergoing CEA, which involved
      the gradual reduction of depth of anesthesia until the patient was capable of
      responding to a verbal stimulus and provide full collaboration while only
      receiving remifentanil. A positive WUT indicated that patient was not able to
      carry out the order. MEASUREMENTS AND MAIN RESULTS: Of 343 patients, 20 (5.8%)
      were shunted due to a positive WUT after cross-clamping in comparison to 45
      patients (12.8%) based on the SPs <or=40 mm Hg criteria. CONCLUSION: Wake-up test
      can be used to directly assess the neurological status in patients undergoing CEA
      to determine whether shunting is required. Our results showed that less patients
      required shunting based on WUT compared to the SP criteria.

PMID- 20150230
TI  - Ten years of monitoring the occupational radiation exposure in Bosnia and
      Herzegovina.
AB  - Monitoring of occupationally exposed persons in Bosnia and Herzegovina started in
      1960s and it was interrupted in 1992. Dosimetry service resumed in 1999 when the
      International Atomic Energy Agency provided Harshaw 4500 TLD-reader and the first
      set of TLDs for the Radiation Protection Centre (RPC) of the Institute of Public
      Health of the Federation of Bosnia and Herzegovina. In January 2009, the RPC
      covered 1279 professionals with personal dosimetry, which is more than 70 % of
      all radiation workers in the country. Most of the TLD users work in medical
      institutions. In period 1999-2003 RPC provided 984 workers with dosemeters. In
      the next 5 y period (2004-2008), the number of persons covered by dosimetry
      increased by an average of 51 %. The mean and collective effective dose in the
      period 1999-2003 were 1.55 mSv and 1.54 personSv, respectively. In the period
      2004-2008, the mean doses changed by 1 % on average, but the collective effective
      dose increased by 53 % for all practices. Mean and collective effective dose were
      1.57 mSv and 2.34 personSv, respectively. The highest personal doses are
      associated with industrial radiography, than exposures in nuclear medicine.
      Radiology plays a significant role in collective dose only, whereas other
      exposures are low. Results correspond to results found in the literature. New
      practices in industry and medicine emphasise the need for more personal
      dosemeters, as well as specialised dosemeters for extremities monitoring, etc.

PMID- 20150231
TI  - Biokinetics of 18F-choline studied in four prostate cancer patients.
AB  - Biokinetic data are important when calculating the absorbed dose to the patients
      and can also be used to find the optimal time between injection and imaging. To
      the authors' knowledge, there are no published biokinetic data in humans for
      (18)F-choline, except some distribution data at single time points. Four patients
      with suspicion of metastases due to biochemical recurrence (measurable prostate
      specific antigen in plasma) after radical prostatectomy were injected with (18)F
      choline. Four whole-body PET/CT images were taken with 1 h interval, starting
      immediately after injection. Blood samples were taken and all urine was collected
      for 3.5 h. The corrected decay activity content in the kidneys was 22-37 % higher
      immediately after injection when compared with the later time points. The highest
      activity concentration was found in kidneys (43 kBq ml(-1)). The organ with
      highest activity content was the liver (11 % of injected activity, % IA). Thirty
      minutes after the injection 4-16 % IA was left in the blood. Less than 9 % IA was
      excreted with the urine during the first 3.5 h after injection.

PMID- 20150232
TI  - AP-2alpha knockout mice exhibit optic cup patterning defects and failure of optic
      stalk morphogenesis.
AB  - Appropriate development of the retina and optic nerve requires that the forebrain
      derived optic neuroepithelium undergoes a precisely coordinated sequence of
      patterning and morphogenetic events, processes which are highly influenced by
      signals from adjacent tissues. Our previous work has suggested that transcription
      factor activating protein-2 alpha (AP-2alpha; Tcfap2a) has a non-cell autonomous
      role in optic cup (OC) development; however, it remained unclear how OC
      abnormalities in AP-2alpha knockout (KO) mice arise at the morphological and
      molecular level. In this study, we show that patterning and morphogenetic defects
      in the AP-2alpha KO optic neuroepithelium begin at the optic vesicle stage.
      During subsequent OC formation, ectopic neural retina and optic stalk-like tissue
      replaced regions of retinal pigment epithelium. AP-2alpha KO eyes also displayed
      coloboma in the ventral retina, and a rare phenotype in which the optic stalk
      completely failed to extend, causing the OCs to be drawn inward to the midline.
      We detected evidence of increased sonic hedgehog signaling in the AP-2alpha KO
      forebrain neuroepithelium, which likely contributed to multiple aspects of the
      ocular phenotype, including expansion of PAX2-positive optic stalk-like tissue
      into the OC. Our data suggest that loss of AP-2alpha in multiple tissues in the
      craniofacial region leads to severe OC and optic stalk abnormalities by
      disturbing the tissue-tissue interactions required for ocular development. In
      view of recent data showing that mutations in human TFAP2A result in similar eye
      defects, the current findings demonstrate that AP-2alpha KO mice provide a
      valuable model for human ocular disease.

PMID- 20150233
TI  - Modulation of imprinted gene network in placenta results in normal development of
      in vitro manipulated mouse embryos.
AB  - Genomic imprinting regulates the expression of a group of genes monoallelically
      expressed in a parent-of-origin specific manner. Allele-specific DNA methylation
      occurs at differentially methylated regions (DMRs) of these genes. We have
      previously shown that in vitro fertilization and embryo culture result in
      methylation defects at the imprinted H19-Igf2 locus at the blastocyst stage. The
      current study was designed to evaluate the consequences of these manipulations on
      genomic imprinting after implantation in the mouse. Blastocysts were produced
      following three experimental conditions: (i) embryos maintained in culture medium
      after in vivo fertilization or (ii) in vitro fertilization and (iii) a control
      group with embryos obtained after in vivo fertilization and timed mating.
      Blastocysts were all transplanted into pseudopregnant females. Embryos and
      placentas were collected on day 10.5 of development. DNA methylation patterns of
      the H19, Igf2, Igf2r and Dlk1-Dio3 DMRs were analyzed by quantitative
      pyrosequencing. In contrast to blastocyst stage, methylation profiles were normal
      both in embryonic and placental tissues after in vitro fertilization and culture.
      Expression of a selected set of imprinting genes from the recently described
      imprinted gene network (IGN) (including Igf2 and H19) was analyzed in placental
      tissues by quantitative RT-PCR. Placentas obtained after in vitro fertilization
      and embryo culture displayed significantly disturbed levels of H19 and Igf2 mRNA,
      as well as of most other genes from the IGN. As embryos were phenotypically
      normal, we hypothesize that the modulation of a coordinated network of imprinted
      genes results in a compensatory process capable of correcting potential
      dysfunction of placenta.

PMID- 20150234
TI  - Trends in health care spending for immigrants in the United States.
AB  - The suspected burden that undocumented immigrants may place on the U.S. health
      care system has been a flashpoint in health care and immigration reform debates.
      An examination of health care spending during 1999-2006 for adult naturalized
      citizens and immigrant noncitizens (which includes some undocumented immigrants)
      finds that the cost of providing health care to immigrants is lower than that of
      providing care to U.S. natives and that immigrants are not contributing
      disproportionately to high health care costs in public programs such as Medicaid.
      However, noncitizen immigrants were found to be more likely than U.S. natives to
      have a health care visit classified as uncompensated care.

PMID- 20150235
TI  - pBaSysBioII: an integrative plasmid generating gfp transcriptional fusions for
      high-throughput analysis of gene expression in Bacillus subtilis.
AB  - Plasmid pBaSysBioII was constructed for high-throughput analysis of gene
      expression in Bacillus subtilis. It is an integrative plasmid with a ligation
      independent cloning (LIC) site, allowing the generation of transcriptional
      gfpmut3 fusions with desired promoters. Integration is by a Campbell-type event
      and is non-mutagenic, placing the fusion at the homologous chromosomal locus.
      Using phoA, murAA, gapB, ptsG and cggR promoters that are responsive to phosphate
      availability, growth rate and carbon source, we show that detailed profiles of
      promoter activity can be established, with responses to changing conditions being
      measurable within 1 min of the stimulus. This makes pBaSysBioII a highly
      versatile tool for real-time gene expression analysis in growing cells of B.
      subtilis.

PMID- 20150236
TI  - The antimicrobial compound reuterin (3-hydroxypropionaldehyde) induces oxidative
      stress via interaction with thiol groups.
AB  - Reuterin is an antimicrobial compound produced by Lactobacillus reuteri, and has
      been proposed to mediate, in part, the probiotic health benefits ascribed to this
      micro-organism. Despite 20 years of investigation, the mechanism of action by
      which reuterin exerts its antimicrobial effects has remained elusive. Here we
      provide evidence that reuterin induces oxidative stress in cells, most likely by
      modifying thiol groups in proteins and small molecules. Escherichia coli cells
      subjected to sublethal levels of reuterin expressed a set of genes that
      overlapped with the set of genes composing the OxyR regulon, which senses and
      responds to various forms of oxidative stress. E. coli cells mutated for oxyR
      were more sensitive to reuterin compared with wild-type cells, further supporting
      a role for reuterin in exerting oxidative stress. The addition of cysteine to E.
      coli or Clostridium difficile growth media prior to exposure to reuterin
      suppressed the antimicrobial effect of reuterin on these bacteria. Interestingly,
      interaction with E. coli stimulated reuterin production or secretion by L.
      reuteri, indicating that contact with other microbes in the gut increases
      reuterin output. Thus, reuterin inhibits bacterial growth by modifying thiol
      groups, which indicates that reuterin negatively affects a large number of
      cellular targets.

PMID- 20150238
TI  - Paradoxical conservation of a set of three cellulose-targeting genes in
      Mycobacterium tuberculosis complex organisms.
AB  - The genome of the tuberculosis agent Mycobacterium tuberculosis encodes a
      putative cellulose-binding protein (CBD2), one candidate cellulase (Cel12), and
      one fully active cellulase (Cel6). This observation is puzzling, because
      cellulose is a major component of plant cell walls, whereas M. tuberculosis is a
      human pathogen without known contact with plants. In order to investigate the
      biological role of such cellulose-targeting genes in M. tuberculosis we report
      here the search for and transcription analysis of this set of genes in the genus
      Mycobacterium. An in silico search for cellulose-targeting orthologues found that
      only 2.5 % of the sequenced bacterial genomes encode the Cel6, Cel12 and CBD2
      gene set simultaneously, including those of the M. tuberculosis complex (MTC)
      members. PCR amplification and sequencing further demonstrated the presence of
      these three genes in five non-sequenced MTC bacteria. Among mycobacteria, the
      combination of Cel6, Cel12 and CBD2 was unique to MTC members, with the exception
      of Mycobacterium bovis BCG Pasteur, which lacked CBD2. RT-PCR in M. tuberculosis
      H37Rv indicated that the three cellulose-targeting genes were transcribed into
      mRNA. The present work shows that MTC organisms are the sole mycobacteria among
      very few organisms to encode the three cellulose-targeting genes CBD2, Cel6 and
      Cel12. Our data point toward a unique, yet unknown, relationship with non-plant
      cellulose-producing hosts such as amoebae.

PMID- 20150237
TI  - Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin
      receptor.
AB  - Meningococcal disease caused by serogroup B Neisseria meningitidis remains an
      important health problem in many parts of the world, and there are currently no
      comprehensive vaccines. Poor immunogenicity, combined with immunological identity
      to human sialic acids, have hindered the development of a serogroup B conjugate
      vaccine, resulting in the development of alternative vaccine candidates,
      including many outer-membrane protein (OMP)-based formulations. However, the
      design of protein-based meningococcal vaccines is complicated by the high level
      of genetic and antigenic diversity of the meningococcus. Knowledge of the extent
      and structuring of this diversity can have implications for the use of particular
      proteins as potential vaccine candidates. With this in mind, the diversity of the
      meningococcal OMP HmbR was investigated among N. meningitidis isolates
      representative of major hyper-invasive lineages. In common with other
      meningococcal antigens, the genetic diversity of hmbR resulted from a combination
      of intraspecies horizontal genetic exchange and de novo mutation. Furthermore,
      genealogical analysis showed an association of hmbR genes with clonal complexes
      and the occurrence of two hmbR families, A and B. Three variable regions (VR1
      VR3), located in loops 2, 3 and 4, were observed with clonal complex structuring
      of VR types. A minority of codons (3.9 %), located within putative surface
      exposed loop regions of a 2D model, were under diversifying selection, indicating
      regions of the protein likely to be subject to immune attack.

PMID- 20150239
TI  - 2,3-Dihydroxypropane-1-sulfonate degraded by Cupriavidus pinatubonensis JMP134:
      purification of dihydroxypropanesulfonate 3-dehydrogenase.
AB  - 2,3-Dihydroxypropane-1-sulfonate (DHPS) is a widespread intermediate in plant and
      algal transformations of sulfoquinovose (SQ) from the plant sulfolipid
      sulfoquinovosyl diacylglycerol. Further, DHPS is recovered quantitatively during
      bacterial degradation of SQ by Klebsiella sp. strain ABR11. DHPS is also a
      putative precursor of sulfolactate in e.g. Ruegeria pomeroyi DSS-3. A
      bioinformatic approach indicated that some 28 organisms with sequenced genomes
      might degrade DHPS inducibly via sulfolactate, with three different desulfonative
      enzymes involved in its degradation in different organisms. The hypothesis for
      Cupriavidus pinatubonensis JMP134 (formerly Ralstonia eutropha) involved a seven
      gene cluster (Reut_C6093-C6087) comprising a LacI-type transcriptional regulator,
      HpsR, a major facilitator superfamily uptake system, HpsU, three NAD(P)(+)
      coupled DHPS dehydrogenases, HpsNOP, and (R)-sulfolactate sulfo-lyase (SuyAB) [EC
      4.4.1.24]. HpsOP effected a DHPS-racemase activity, and HpsN oxidized (R)-DHPS to
      (R)-sulfolactate. The hypothesis for Roseovarius nubinhibens ISM was similar, but
      involved a tripartite ATP-independent transport system for DHPS, HpsKLM, and two
      different desulfonative enzymes, (S)-cysteate sulfo-lyase [EC 4.4.1.25] and
      sulfoacetaldehyde acetyltransferase (Xsc) [EC 2.3.3.15]. Representative organisms
      were found to grow with DHPS and release sulfate. C. pinatubonensis JMP134 was
      found to express at least one NAD(P)(+)-coupled DHPS dehydrogenase inducibly, and
      three different peaks of activity were separated by anion-exchange
      chromatography. Protein bands (SDS-PAGE) were subjected to peptide-mass
      fingerprinting, which identified the corresponding genes (hpsNOP). Purified HpsN
      converted DHPS to sulfolactate. Reverse-transcription PCR confirmed that hpsNOUP
      were transcribed inducibly in strain JMP134, and that hpsKLM and hpsNOP were
      transcribed in strain ISM. DHPS degradation is widespread and diverse, implying
      that DHPS is common in marine and terrestrial environments.

PMID- 20150240
TI  - Prevalence of Fst-like toxin-antitoxin systems.

PMID- 20150241
TI  - Pseudomonas aeruginosa secreted factors impair biofilm development in Candida
      albicans.
AB  - Signal-mediated interactions between the human opportunistic pathogens
      Pseudomonas aeruginosa and Candida albicans affect virulence traits in both
      organisms. Phenotypic studies revealed that bacterial supernatant from four P.
      aeruginosa strains strongly reduced the ability of C. albicans to form biofilms
      on silicone. This was largely a consequence of inhibition of biofilm maturation,
      a phenomenon also observed with supernatant prepared from non-clinical bacterial
      species. The effects of supernatant on biofilm formation were not mediated via
      interference with the yeast-hyphal morphological switch and occurred regardless
      of the level of homoserine lactone (HSL) produced, indicating that the effect is
      HSL-independent. A transcriptome analysis to dissect the effects of the P.
      aeruginosa supernatants on gene expression in the early stages of C. albicans
      biofilm formation identified 238 genes that exhibited reproducible changes in
      expression in response to all four supernatants. In particular, there was a
      strong increase in the expression of genes related to drug or toxin efflux and a
      decrease in expression of genes associated with adhesion and biofilm formation.
      Furthermore, expression of YWP1, which encodes a protein known to inhibit biofilm
      formation, was significantly increased. Biofilm formation is a key aspect of C.
      albicans infections, therefore the capacity of P. aeruginosa to antagonize this
      has clear biomedical implications.

PMID- 20150242
TI  - Novel insertion and deletion mutants of RpoB that render Mycobacterium smegmatis
      RNA polymerase resistant to rifampicin-mediated inhibition of transcription.
AB  - The startling increase in the occurrence of rifampicin (Rif) resistance in the
      clinical isolates of Mycobacterium tuberculosis worldwide is posing a serious
      concern to tuberculosis management. The majority of Rif resistance in bacteria
      arises from mutations in the RpoB subunit of the RNA polymerase. We isolated M.
      smegmatis strains harbouring either an insertion (6 aa) or a deletion (10 aa) in
      their RpoB proteins. Although these strains showed a compromised fitness for
      growth in 7H9 Middlebrook medium, their resistance to Rif was remarkably high.
      The attenuated growth of the strains correlated with decreased specific
      activities of the RNA polymerases from the mutants. While the RNA polymerases
      from the parent or a mutant strain (harbouring a frequently occurring mutation,
      H442Y, in RpoB) were susceptible to Rif-mediated inhibition of transcription from
      calf thymus DNA, those from the insertion and deletion mutants were essentially
      refractory to such inhibition. Three-dimensional structure modelling revealed
      that the RpoB amino acids that interact with Rif are either deleted or unable to
      interact with Rif due to their unsuitable spatial positioning in these mutants.
      We discuss possible uses of the RpoB mutants in studying transcriptional
      regulation in mycobacteria and as potential targets for drug design.

PMID- 20150243
TI  - Analysis of the liver mitochondrial proteome in response to ethanol and S
      adenosylmethionine treatments: novel molecular targets of disease and
      hepatoprotection.
AB  - S-adenosylmethionine (SAM) minimizes alcohol hepatotoxicity; however, the
      molecular mechanisms responsible for SAM hepatoprotection remain unknown. Herein,
      we use proteomics to determine whether the hepatoprotective action of SAM against
      early-stage alcoholic liver disease is linked to alterations in the mitochondrial
      proteome. For this, male rats were fed control or ethanol-containing liquid diets
      +/- SAM and liver mitochondria were prepared for proteomic analysis. Two
      dimensional isoelectric focusing (2D IEF/SDS-PAGE) and blue native gel
      electrophoresis (BN-PAGE) were used to determine changes in matrix and oxidative
      phosphorylation (OxPhos) proteins, respectively. SAM coadministration minimized
      alcohol-dependent inflammation and preserved mitochondrial respiration. SAM
      supplementation preserved liver SAM levels in ethanol-fed rats; however,
      mitochondrial SAM levels were increased by ethanol and SAM treatments. With use
      of 2D IEF/SDS-PAGE, 30 proteins showed significant changes in abundance in
      response to ethanol, SAM, or both. Classes of proteins affected by ethanol and
      SAM treatments were chaperones, beta oxidation proteins, sulfur metabolism
      proteins, and dehydrogenase enzymes involved in methionine, glycine, and choline
      metabolism. BN-PAGE revealed novel changes in the levels of 19 OxPhos proteins in
      response to ethanol, SAM, or both. Ethanol- and SAM-dependent alterations in the
      proteome were not linked to corresponding changes in gene expression. In
      conclusion, ethanol and SAM treatment led to multiple changes in the liver
      mitochondrial proteome. The protective effects of SAM against alcohol toxicity
      are mediated, in part, through maintenance of proteins involved in key
      mitochondrial energy conserving and biosynthetic pathways. This study
      demonstrates that SAM may be a promising candidate for treatment of alcoholic
      liver disease.

PMID- 20150244
TI  - Putative anion transporter-1 (Pat-1, Slc26a6) contributes to intracellular pH
      regulation during H+-dipeptide transport in duodenal villous epithelium.
AB  - The majority of dietary amino acids are absorbed via the H(+)-di-/tripeptide
      transporter Pept1 of the small intestine. Proton influx via Pept1 requires
      maintenance of intracellular pH (pH(i)) to sustain the driving force for peptide
      absorption. The apical membrane Na(+)/H(+) exchanger Nhe3 plays a major role in
      minimizing epithelial acidification during H(+)-di-/tripeptide absorption.
      However, the contributions of HCO(3)(-)-dependent transporters to this process
      have not been elucidated. In this study, we investigate the role of putative
      anion transporter-1 (Pat-1), an apical membrane anion exchanger, in epithelial
      pH(i) regulation during H(+)-peptide absorption. Using wild-type (WT) and Pat-1(
      ) mice, Ussing chambers were employed to measure the short-circuit current
      (I(sc)) associated with Pept1-mediated glycyl-sarcosine (Gly-Sar) absorption.
      Microfluorometry was used to measure pH(i) and Cl(-)/HCO(3)(-) exchange in the
      upper villous epithelium. In CO(2)/HCO(3)(-)-buffered Ringers, WT small intestine
      showed significant Gly-Sar-induced I(sc) and efficient pH(i) regulation during
      pharmacological inhibition of Nhe3 activity. In contrast, epithelial
      acidification and reduced I(sc) response to Gly-Sar exposure occurred during
      pharmacological inhibition of Cl(-)/HCO(3)(-) exchange and in the Pat-1(-)
      intestine. Pat-1 interacts with carbonic anhydrase II (CAII), and studies using
      CAII(-) intestine or the pharmacological inhibitor methazolamide on WT intestine
      resulted in increased epithelial acidification during Gly-Sar exposure. Increased
      epithelial acidification during Gly-Sar exposure also occurred in WT intestine
      during inhibition of luminal extracellular CA activity. Measurement of Cl(
      )/HCO(3)(-) exchange in the presence of Gly-Sar revealed an increased rate of Cl(
      )(OUT)/HCO(3)(-)(IN) exchange that was both Pat-1 dependent and CA dependent. In
      conclusion, Pat-1 Cl(-)/HCO(3)(-) exchange contributes to pH(i) regulation in the
      villous epithelium during H(+)-dipeptide absorption, possibly by providing a
      HCO(3)(-) import pathway.

PMID- 20150247
TI  - Salvage therapy with (177)Lu-octreotate in patients with bronchial and
      gastroenteropancreatic neuroendocrine tumors.
AB  - Regular therapy with the radiolabeled somatostatin analog (177)Lu-octreotate
      (22.2-29.6 GBq) in patients with gastroenteropancreatic or bronchial
      neuroendocrine tumors results in tumor remission in 46% of patients, including
      minor response. We present the effects of additional therapy with (177)Lu
      octreotate in patients in whom progressive disease developed after an initial
      benefit from regular therapy. METHODS: Thirty-three patients with progressive
      disease after an initial radiologic or clinical response were treated with
      additional cycles of (177)Lu-octreotate. The intended cumulative dose of
      additional therapy was 14.8 GBq in 2 cycles. Responses were evaluated using
      Southwest Oncology Group criteria, including minor response (tumor size reduction
      of >or=25% and <50%). RESULTS: Median time to progression (TTP) after regular
      therapy was 27 mo. In 4 patients, the intended cumulative dose was not achieved
      (2 had progressive disease, 2 had long-lasting thrombocytopenia). Hematologic
      toxicity grade 3 was observed in 4 patients, and grade 4, in 1. The median follow
      up time was 16 mo (range, 1-40 mo). No kidney failure or myelodysplastic syndrome
      was observed. Renewed tumor regression was observed in 8 patients (2 partial
      remission, 6 minor response), and 8 patients had stable disease. Median TTP was
      17 mo. Treatment outcome was less favorable in patients with a short TTP after
      regular cycles. Treatment effects in patients with pancreatic neuroendocrine
      tumors were similar to those in patients with other gastroenteropancreatic
      neuroendocrine tumors. CONCLUSION: Most patients tolerated additional cycles with
      (177)Lu-octreotate well. None developed serious delayed adverse events.
      Additional cycles with (177)Lu-octreotate can have antitumor effects, but effects
      were less than for the regular cycles. This may be because of a worse clinical
      condition, more extensive tumor burden, or changed tumor characteristics. We
      conclude that this salvage therapy can be effective and is safe.

PMID- 20150245
TI  - Interstitial cells of Cajal in the cynomolgus monkey rectoanal region and their
      relationship to sympathetic and nitrergic nerves.
AB  - The morphology of interstitial cells of Cajal (ICC) in the circular muscle layer
      of the cynomolgus monkey internal anal sphincter (IAS) and rectum and their
      relationship to sympathetic and nitrergic nerves were compared by dual-labeling
      immunohistochemistry. Contractile studies confirmed that nitrergic nerves
      participate in neural inhibition in both regions whereas sympathetic nerves serve
      as excitatory motor nerves only in the IAS. Muscle bundles extended from
      myenteric to submucosal edge in rectum but in the IAS bundles were further
      divided into "minibundles" each surrounded by connective tissue. Dual labeling of
      KIT and smooth muscle myosin revealed KIT-positive stellate-shaped ICC (ICC-IAS)
      within each minibundle. In the rectum intramuscular ICC (ICC-IM) were spindle
      shaped whereas stellate-shaped ICC were located at the myenteric surface (ICC
      MY). ICC were absent from both the myenteric and submucosal surfaces of the IAS.
      Nitrergic nerves (identified with anti-neuronal nitric oxide synthase antibodies
      or NADPH diaphorase activity) and sympathetic nerves (identified with anti
      tyrosine hydroxylase antibody) each formed a plexus at the myenteric surface of
      the rectum but not the IAS. Intramuscular neuronal nitric oxide synthase- and
      tyrosine hydroxylase-positive fibers were present in both regions but were only
      closely associated with ICC-IM in rectum. Minimal association was also noted
      between ICC-IAS and cells expressing the nonspecific neuronal marker PGP9.5. In
      conclusion, the morphology of rectal ICC-IM and ICC-MY is similar to that
      described elsewhere in the gastrointestinal tract whereas ICC-IAS are unique. The
      distribution of stellate-shaped ICC-IAS throughout the musculature and their
      absence from both the myenteric and submucosal surfaces suggest that ICC-IAS may
      serve as pacemaker cells in this muscle whereas their limited relationship to
      nerves suggests that they are not involved in neuromuscular transmission.
      Additionally, the presence of numerous minibundles, each containing both ICC-IAS
      and nerves, suggests that this muscle functions as a multiunit type muscle.

PMID- 20150248
TI  - (99m)Tc(CO)3(NTA): a (99m)Tc renal tracer with pharmacokinetic properties
      comparable to those of (131)I-OIH in healthy volunteers.
AB  - Studies in rats showed that the pharmacokinetics of the tricarbonyl core
      radiopharmaceutical (99m)Tc(CO)(3)-nitrilotriacetic acid, (99m)Tc(CO)(3)(NTA),
      were essentially identical to those of (131)I ortho-iodohippuran ((131)I-OIH),
      the clinical gold standard for the measurement of effective renal plasma flow.
      Our objective was to compare the pharmacokinetics of these 2 tracers in healthy
      volunteers. METHODS: (99m)Tc(CO)(3)(NTA) was prepared with commercially available
      NTA and a commercially available kit and isolated by reversed-phase high
      performance liquid chromatography. Approximately 74 MBq (2 mCi) of
      (99m)Tc(CO)(3)(NTA) were coinjected with 9.25 MBq (250 microCi) of (131)I-OIH in
      9 volunteers, and simultaneous imaging of each tracer was performed for 24 min.
      Plasma clearances were determined from 8 blood samples obtained 3-90 min after
      injection using the single-injection, 2-compartment model. Plasma protein
      binding, red cell uptake, and percentage injected dose in the urine at 30 and 180
      min were determined. RESULTS: There was no difference in the plasma clearances of
      (99m)Tc(CO)(3)(NTA) and (131)I-OIH, 475 +/- 105 mL/min versus 472 +/- 108 mL/min,
      respectively. The plasma protein binding and red cell uptake of
      (99m)Tc(CO)(3)(NTA) were 43% +/- 5% and 9% +/- 6%, respectively; both values were
      significantly lower (P < 0.001) than the plasma protein binding (75% +/- 3%) and
      red cell uptake (17% +/- 5%) of (131)I-OIH. There was no significant difference
      in the percentage injected dose recovered in the urine at 30 min and at 3 h; for
      comparison, the percentage dose in the urine at 3 h was 91% +/- 4% for
      (99m)Tc(CO)(3)(NTA) and 91% +/- 6% for (131)I-OIH (P = 0.96). Image quality with
      (99m)Tc(CO)(3)(NTA) was excellent, and the renogram parameters were similar to
      those of (131)I-OIH. CONCLUSION: Preliminary results in healthy volunteers
      suggest that the pharmacokinetic behavior of (99m)Tc(CO)(3)(NTA) is comparable to
      that of (131)I-OIH.

PMID- 20150249
TI  - Standardized uptake values of (68)Ga-DOTANOC PET: a promising prognostic tool in
      neuroendocrine tumors.
AB  - Despite the fact that several studies have been published regarding the
      prognostic factors of neuroendocrine tumors (NETs), there are some cases in which
      available data are not sufficient to predict disease progression and to define a
      correct therapeutic approach. To our knowledge, the role of maximum standardized
      uptake value (SUVmax) as a prognostic factor has never been studied in NET
      patients. Therefore, we prospectively investigated whether (68)Ga-[1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide ((68)Ga
      DOTANOC) PET SUVmax could be used as an accurate noninvasive marker for disease
      prognosis. METHODS: Forty-seven patients with NETs were studied with (68)Ga
      DOTANOC PET. All patients underwent a baseline visit and laboratory and
      radiologic examinations. Follow-up was performed in all cases. RESULTS: SUVmax
      was significantly higher in patients with pancreatic NET and in those with well
      differentiated NETs. Moreover, SUVmax was significantly higher in patients with
      an elevated expression of 2A-somatostatin receptor. During the follow-up, the
      disease was stable or presented a partial response in 25 patients, and in 19
      cases the disease progressed. The patients with stable disease or a partial
      response had an SUVmax significantly higher than did those in the progressive
      disease group, with the best cutoff ranging from 17.9 to 19.3. At univariate and
      multivariate analysis, the significant positive prognostic factors were well
      differentiated NET, an SUVmax of 19.3 or more, and a combined treatment with long
      acting somatostatin analogs and radiolabeled somatostatin analogs. CONCLUSION: We
      demonstrated, for the first time to our knowledge, that (68)Ga-DOTANOC PET SUVmax
      correlates with the clinical and pathologic features of NETs and is also an
      accurate prognostic index.

PMID- 20150250
TI  - Economic evaluation of PET and PET/CT in oncology: evidence and methodologic
      approaches.
AB  - PET and PET/CT have changed the diagnostic algorithm in oncology. Health care
      systems worldwide have recently approved reimbursement for PET and PET/CT for
      staging of non-small cell lung cancer and differential diagnosis of solitary
      pulmonary nodules because PET and PET/CT have been found to be cost-effective for
      those uses. Additional indications that are covered by health care systems in the
      United States and several European countries include staging of gastrointestinal
      tract cancers, breast cancer, malignant lymphoma, melanoma, and head and neck
      cancers. Regarding these indications, diagnostic effectiveness and superiority
      over conventional imaging modalities have been shown, whereas cost-effectiveness
      has been demonstrated only in part. This article reports on the current knowledge
      of economic evaluations of PET and PET/CT in oncologic applications. Because more
      economic evaluations are needed for several clinical indications, we also report
      on the methodologies for conducting economic evaluations of diagnostic tests and
      suggest an approach toward the implementation of these tests in future clinical
      studies.

PMID- 20150251
TI  - Side effects profile in humans of (11)C-(+)-PHNO, a dopamine D(2/3) agonist
      ligand for PET.

PMID- 20150252
TI  - PET/MRI: paving the way for the next generation of clinical multimodality imaging
      applications.
AB  - Multimodality imaging and, more specifically, the combination of PET and CT has
      matured into an important diagnostic tool. During the same period, concepts for
      PET scanners integrated into an MR tomograph have emerged. The excellent soft
      tissue contrast of MRI and the multifunctional imaging options it offers, such as
      spectroscopy, functional MRI, and arterial spin labeling, complement the
      molecular information of PET. The development of a fully integrated PET/MRI
      system is technologically challenging. It requires not only significant
      modifications of the PET detector to make it compact and insensitive to magnetic
      fields but also a major redesign of the MRI hardware.

PMID- 20150253
TI  - The effect of age, menopausal state, and breast density on (18)F-FDG uptake in
      normal glandular breast tissue.
AB  - Theoretically, the degree of (18)F-FDG uptake in the glandular tissues of the
      normal breast can affect the detection of breast cancer. The aim of this
      prospective study was to investigate relationships among age, menopausal state,
      and breast density and determine whether they affect (18)F-FDG uptake in normal
      glandular breast tissue. METHODS: Among 250 newly diagnosed breast cancer
      patients, 149 patients (mean age +/- SD, 50.9 +/- 9.70 y; range, 32-77 y) were
      analyzed because they had normal contralateral breasts confirmed by MRI,
      mammography, and (18)F-FDG PET examinations. PET images were acquired 60 +/- 2
      min after the administration of (18)F-FDG (5.2 MBq/kg of body weight). The
      maximum and average standardized uptake value (SUVmax and SUVavg, respectively)
      of (18)F-FDG were calculated in the normal breast. Patients were divided into
      groups according to qualitative breast density and menopausal state. Descriptive
      statistics and 2-factorial analysis of covariance were used to assess the effects
      of qualitative breast density, menopausal state, and age on SUVmax and SUVavg.
      Pearson chi(2) was used to test the relationship between menopausal state and
      qualitative breast density. RESULTS: The average age of patients with nondense
      breasts was significantly higher than that of patients with dense breasts (P <
      0.01). Also, breast density related to menopausal state (P < 0.05). Dense breasts
      had an average SUVmax of 1.243 and mean SUVavg of 0.694, whereas nondense breasts
      had a mean SUVmax of 0.997 and mean SUVavg of 0.592. Analysis of covariance
      indicated that density and the linear effect of age were significant with regard
      to both SUVmax and SUVavg. After removing the linear effect of age, menopausal
      state had no effect on SUVmax and SUVavg. CONCLUSION: (18)F-FDG uptake
      significantly decreases as age increases and breast density decreases. Age and
      qualitative breast density are independent factors and significantly affect (18)F
      FDG uptake for both SUVmax and SUVavg. Menopausal state had no effect on SUVmax
      and SUVavg.

PMID- 20150254
TI  - High-contrast PET of melanoma using (18)F-MEL050, a selective probe for melanin
      with predominantly renal clearance.
AB  - The aim of this study was to evaluate the novel probe (18)F-6-fluoro-N-[2
      (diethylamino)ethyl] pyridine-3-carboxamide ((18)F-MEL050) for the imaging of
      primary and metastatic melanoma. METHODS: PET using (18)F-MEL050 was performed in
      murine models of melanoma. The specificity of (18)F-MEL050 was studied by
      comparing its accumulation in pigmented B16-F0 allograft tumors with that of
      human amelanotic A375 xenografts using PET and high-resolution autoradiography.
      (18)F-MEL050 PET results were compared with (18)F-FDG PET, the current standard
      in melanoma molecular imaging. To test the ability of (18)F-MEL050 to assess the
      metastatic spread of melanoma, a murine model of lung metastasis was imaged by
      PET/CT, and results correlated with physical assessment of tumor burden in the
      lungs. RESULTS: In pigmented B16-F0 grafts, (18)F-MEL050 PET yielded a tumor-to
      background ratio of approximately 20:1 at 1 h and greater than 50:1 at 2 and 3 h.
      In the B16-F0 melanoma allograft model, tumor-to-background ratio was more than 9
      fold higher for (18)F-MEL050 than for (18)F-FDG (50.9 +/- 6.9 vs. 5.8 +/- 0.5).
      No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of
      (18)F-MEL050 was evident in metastatic lesions in the lungs of B16-BL6 tumor
      bearing mice on PET at 2 h after tracer injection, with high concordance between
      (18)F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy.
      CONCLUSION: (18)F-MEL050 has a rapid tumor uptake and high retention with
      specificity for melanin, suggesting great potential for noninvasive clinical
      evaluation of suspected metastatic melanoma.

PMID- 20150255
TI  - Impurity in (68)Ga-peptide preparation using processed generator eluate.

PMID- 20150256
TI  - Reduction of the ring size of radiolabeled lactam bridge-cyclized alpha-MSH
      peptide, resulting in enhanced melanoma uptake.
AB  - The purpose of this study was to examine the profound effect of the ring size of
      the radiolabeled lactam bridge-cyclized alpha-melanocyte-stimulating hormone
      (alpha-MSH) peptide on its melanoma-targeting properties. METHODS: A novel cyclic
      alpha-MSH peptide, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Nle
      c[Asp-His-D-Phe-Arg-Trp-Lys]-CONH(2) (DOTA-Nle-CycMSH(hex)), was synthesized and
      radiolabeled with (111)In. The melanocortin-1 receptor-binding affinity of DOTA
      Nle-CycMSH(hex) was determined in B16/F1 melanoma cells. The internalization and
      efflux of (111)In-DOTA-Nle-CycMSH(hex) were examined in B16/F1 cells. The
      melanoma-targeting properties and SPECT/CT characteristics of (111)In-DOTA-Nle
      CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice. RESULTS: DOTA
      Nle-CycMSH(hex) displayed 1.77 nM receptor-binding affinity. (111)In-DOTA-Nle
      CycMSH(hex) exhibited rapid internalization and extended retention in B16/F1
      cells. The tumor uptake of (111)In-DOTA-Nle-CycMSH(hex) was 24.94% +/- 4.58% and
      10.53% +/- 1.11% injected dose per gram at 0.5 and 24 h after injection,
      respectively. Greater than 82% of the injected radioactivity was cleared through
      the urinary system by 2 h after injection. The tumor-to-kidney uptake ratios
      reached 2.04 and 1.70 at 2 and 4 h after injection, respectively. Flank melanoma
      tumors were clearly visualized by SPECT/CT using (111)In-DOTA-Nle-CycMSH(hex) as
      an imaging probe at 2 and 24 h after injection. The radioactivity accumulation in
      normal organs, except for the kidneys, was low at 2, 4, and 24 h after injection.
      CONCLUSION: The reduction of the peptide ring size dramatically increased the
      melanoma uptake and decreased the renal uptake of (111)In-DOTA-Nle-CycMSH(hex),
      providing a new insight into the design of a novel radiolabeled lactam bridge
      cyclized alpha-MSH peptide for melanoma imaging and treatment.

PMID- 20150257
TI  - Radioimmunotherapy with anti-CD66 antibody: improving the biodistribution using a
      physiologically based pharmacokinetic model.
AB  - To improve radioimmunotherapy with anti-CD66 antibody, a physiologically based
      pharmacokinetic (PBPK) model was developed that was capable of describing the
      biodistribution and extrapolating between different doses of anti-CD66 antibody.
      METHODS: The biodistribution of the (111)In-labeled anti-CD66 antibody of 8
      patients with acute leukemia was measured. The data were fitted to 2 PBPK models.
      Model A incorporated effective values for antibody binding, and model B
      explicitly described mono- and bivalent binding. The best model was selected
      using the corrected Akaike information criterion. The predictive power of the
      model was validated comparing simulations and (90)Y-anti-CD66 serum measurements.
      The amount of antibody (range, 0.1-4 mg) leading to the most favorable
      therapeutic distribution was determined using simulations. RESULTS: Model B was
      better supported by the data. The fits of the selected model were good (adjusted
      R(2) > 0.91), and the estimated parameters were in a physiologically reasonable
      range. The median deviation of the predicted and measured (90)Y-anti-CD66 serum
      concentration values and the residence times were 24% (range, 17%-31%) and 9%
      (range, 1%-64%), respectively. The validated model predicted considerably
      different biodistributions for dosimetry and therapeutic settings. The smallest
      (0.1 mg) simulated amount of antibody resulted in the most favorable therapeutic
      biodistribution. CONCLUSION: The developed model is capable of adequately
      describing the anti-CD66 antibody biodistribution and accurately predicting the
      time-activity serum curve of (90)Y-anti-CD66 antibody and the therapeutic serum
      residence time. Simulations indicate that an improvement of radioimmunotherapy
      with anti-CD66 antibody is achievable by reducing the amount of administered
      antibody; for example, the residence time of the red marrow could be increased by
      a factor of 1.9 +/- 0.3 using 0.27 mg of anti-CD66 antibody.

PMID- 20150258
TI  - Targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with contrast
      microbubbles conjugated to integrin-binding knottin peptides.
AB  - Targeted contrast-enhanced ultrasound imaging is increasingly being recognized as
      a powerful imaging tool for the detection and quantification of tumor
      angiogenesis at the molecular level. The purpose of this study was to develop and
      test a new class of targeting ligands for targeted contrast-enhanced ultrasound
      imaging of tumor angiogenesis with small, conformationally constrained peptides
      that can be coupled to the surface of ultrasound contrast agents. METHODS:
      Directed evolution was used to engineer a small, disulfide-constrained cystine
      knot (knottin) peptide that bound to alpha(v)beta(3) integrins with a low
      nanomolar affinity (Knottin(Integrin)). A targeted contrast-enhanced ultrasound
      imaging contrast agent was created by attaching Knottin(Integrin) to the shell of
      perfluorocarbon-filled microbubbles (MB-Knottin(Integrin)). A knottin peptide
      with a scrambled sequence was used to create control microbubbles (MB
      Knottin(Scrambled)). The binding of MB-Knottin(Integrin) and MB
      Knottin(Scrambled) to alpha(v)beta(3) integrin-positive cells and control cells
      was assessed in cell culture binding experiments and compared with that of
      microbubbles coupled to an anti-alpha(v)beta(3) integrin monoclonal antibody
      (MB(alphavbeta3)) and microbubbles coupled to the peptidomimetic agent c(RGDfK)
      (MB(cRGD)). The in vivo imaging signals of contrast-enhanced ultrasound with the
      different types of microbubbles were quantified in 42 mice bearing human ovarian
      adenocarcinoma xenograft tumors by use of a high-resolution 40-MHz ultrasound
      system. RESULTS: MB-Knottin(Integrin) attached significantly more to
      alpha(v)beta(3) integrin-positive cells (1.76 +/- 0.49 [mean +/- SD] microbubbles
      per cell) than to control cells (0.07 +/- 0.006). Control MB-Knottin(Scrambled)
      adhered less to alpha(v)beta(3) integrin-positive cells (0.15 +/- 0.12) than MB
      Knottin(Integrin). After blocking of integrins, the attachment of MB
      Knottin(Integrin) to alpha(v)beta(3) integrin-positive cells decreased
      significantly. The in vivo ultrasound imaging signal was significantly higher
      after the administration of MB-Knottin(Integrin) than after the administration of
      MB(alphavbeta3) or control MB-Knottin(Scrambled). After in vivo blocking of
      integrin receptors, the imaging signal after the administration of MB
      Knottin(Integrin) decreased significantly (by 64%). The imaging signals after the
      administration of MB-Knottin(Integrin) were not significantly different in the
      groups of tumor-bearing mice imaged with MB-Knottin(Integrin) and with MB(cRGD).
      Ex vivo immunofluorescence confirmed integrin expression on endothelial cells of
      human ovarian adenocarcinoma xenograft tumors. CONCLUSION: Integrin-binding
      knottin peptides can be conjugated to the surface of microbubbles and used for in
      vivo targeted contrast-enhanced ultrasound imaging of tumor angiogenesis. Our
      results demonstrate that microbubbles conjugated to small peptide-targeting
      ligands provide imaging signals higher than those provided by a large antibody
      molecule.

PMID- 20150260
TI  - Paraaortic sentinel lymph nodes: toward optimal detection and intraoperative
      localization using SPECT/CT and intraoperative real-time imaging.
AB  - Paraaortic sentinel node biopsy may be a challenging procedure because the
      sentinel nodes are located retroperitoneally in close proximity to vital
      structures. The purpose of this study was to describe and evaluate the value of
      preoperative SPECT/CT for lymphatic mapping, and a portable gamma-camera for
      intraoperative radioguidance, in patients with paraaortic sentinel nodes.
      METHODS: We evaluated our practice in 18 patients, who were treated at The
      Netherlands Cancer Institute with sentinel lymphadenectomy for different urologic
      malignancies and showed paraaortic drainage on preoperative images. After
      intratumoral injection of (99m)Tc-nanocolloid, the patients underwent sequential
      planar lymphoscintigraphy, hybrid SPECT/CT, and sentinel lymphadenectomy.
      Intraoperative node detection and localization were guided by a laparoscopic
      gamma-probe and a portable gamma-camera. This gamma-camera was set to display
      both the (99m)Tc signal and the (125)I-seed signal. This (125)I seed was placed
      on top of the gamma-probe, functioning as a pointer on screen, thus enabling real
      time sentinel node localization with the gamma-camera. RESULTS: In 16 patients
      with midabdominal drainage on planar images and in 2 patients with
      nonvisualization on planar images, SPECT/CT showed clear localization of
      paraaortic sentinel nodes in relation to the abdominal vessels. Five patients
      underwent open surgery, and 13 patients underwent laparoscopy. The paraaortic
      sentinel nodes were successfully localized and removed in 15 patients with the
      help of the portable gamma-camera and gamma-probe and in 3 patients with the
      gamma-probe only. In 1 patient, the paraaortic sentinel node showed a metastasis.
      CONCLUSION: If retroperitoneal drainage is expected, SPECT/CT provides good
      detection and clear localization of sentinel nodes in relation to anatomic
      structures. Detection and removal of paraaortic sentinel nodes by means of a
      laparoscopic gamma-probe and real-time imaging with a portable gamma-camera is a
      successful method with high intraoperative detection rates.

PMID- 20150261
TI  - Cellular dosimetry of (111)In using monte carlo N-particle computer code:
      comparison with analytic methods and correlation with in vitro cytotoxicity.
AB  - Our objective was to compare Monte Carlo N-particle (MCNP) self- and cross-doses
      from (111)In to the nucleus of breast cancer cells with doses calculated by
      reported analytic methods (Goddu et al. and Farragi et al.). A further objective
      was to determine whether the MCNP-predicted surviving fraction (SF) of breast
      cancer cells exposed in vitro to (111)In-labeled diethylenetriaminepentaacetic
      acid human epidermal growth factor ((111)In-DTPA-hEGF) could accurately predict
      the experimentally determined values. METHODS: MCNP was used to simulate the
      transport of electrons emitted by (111)In from the cell surface, cytoplasm, or
      nucleus. The doses to the nucleus per decay (S values) were calculated for single
      cells, closely packed monolayer cells, or cell clusters. The cell and nucleus
      dimensions of 6 breast cancer cell lines were measured, and cell line-specific S
      values were calculated. RESULTS: For self-doses, MCNP S values of nucleus to
      nucleus agreed very well with those of Goddu et al. (ratio of S values using
      analytic methods vs. MCNP = 0.962-0.995) and Faraggi et al. (ratio = 1.011
      1.024). MCNP S values of cytoplasm and cell surface to nucleus compared fairly
      well with the reported values (ratio = 0.662-1.534 for Goddu et al.; 0.944-1.129
      for Faraggi et al.). For cross doses, the S values to the nucleus were
      independent of (111)In subcellular distribution but increased with cluster size.
      S values for monolayer cells were significantly different from those of single
      cells and cell clusters. The MCNP-predicted SF for monolayer MDA-MB-468, MDA-MB
      231, and MCF-7 cells agreed with the experimental data (relative error of 3.1%, 
      1.0%, and 1.7%). The single-cell and cell cluster models were less accurate in
      predicting the SF. For MDA-MB-468 cells, relative error was 8.1% using the single
      cell model and -54% to -67% using the cell cluster model. Individual cell-line
      dimensions had large effects on S values and were needed to estimate doses and SF
      accurately. CONCLUSION: MCNP simulation compared well with the reported analytic
      methods in the calculation of subcellular S values for single cells and cell
      clusters. Application of a monolayer model was most accurate in predicting the SF
      of breast cancer cells exposed in vitro to (111)In-DTPA-hEGF.

PMID- 20150262
TI  - The twilight saga of insulin administration in hyperglycemic patients undergoing
      (18)F-FDG PET.

PMID- 20150263
TI  - Imaging of CTLA4 blockade-induced cell replication with (18)F-FLT PET in patients
      with advanced melanoma treated with tremelimumab.
AB  - Preclinical models predict that blockade of the coinhibitory molecule cytotoxic T
      lymphocyte-associated antigen 4 (CTLA4) on lymphocytes results in the release of
      a cell cycle inhibitory checkpoint, allowing lymphocyte proliferation, tumor
      targeting, and regression. However, there is a paucity of data demonstrating that
      lymphocyte proliferation does occur in humans treated with CTLA4-blocking
      antibodies. METHODS: We tested the role of whole-body molecular imaging in
      patients with advanced melanoma receiving the CTLA4-blocking antibody
      tremelimumab, allowing the analysis of changes in glucose metabolism using the
      PET probe (18)F-FDG and cell replication with the PET probe 3'-deoxy-3'-(18)F
      fluorothymidine ((18)F-FLT). RESULTS: PET/CT scans obtained at a median of 2 mo
      after initial dosing did not demonstrate significant changes in lesion size or
      (18)F-FDG or (18)F-FLT uptake when focusing on metastatic lesions. Similarly,
      there was no difference in (18)F-FDG uptake in the non-melanoma-involved spleen.
      However, there were significant increases in standardized uptake values for (18)F
      FLT in the spleen using post- and pretremelimumab treatment scans. CONCLUSION:
      Molecular imaging with the PET probe (18)F-FLT allows mapping and noninvasive
      imaging of cell proliferation in secondary lymphoid organs after CTLA4 blockade
      in patients with metastatic melanoma.

PMID- 20150264
TI  - The Monte Carlo method in nuclear medicine: current uses and future potential.

PMID- 20150265
TI  - Arterial wall dosimetry for non-Hodgkin lymphoma patients treated with
      radioimmunotherapy.
AB  - Tumors in non-Hodgkin lymphoma (NHL) patients are often proximal to the major
      blood vessels in the abdomen or neck. In external-beam radiotherapy, these tumors
      present a challenge because imaging resolution prevents the beam from being
      targeted to the tumor lesion without also irradiating the artery wall. This
      problem has led to potentially life-threatening delayed toxicity. Because
      radioimmunotherapy has resulted in long-term survival of NHL patients, we
      investigated whether the absorbed dose (AD) to the artery wall in
      radioimmunotherapy of NHL is of potential concern for delayed toxicity. SPECT
      resolution is not sufficient to enable dosimetric analysis of anatomic features
      of the thickness of the aortic wall. Therefore, we present a model of aortic wall
      toxicity based on data from 4 patients treated with (131)I-tositumomab. METHODS:
      Four NHL patients with periaortic tumors were administered pretherapeutic (131)I
      tositumomab. Abdominal SPECT and whole-body planar images were obtained at 48,
      72, and 144 h after tracer administration. Blood-pool activity concentrations
      were obtained from regions of interest drawn on the heart on the planar images.
      Tumor and blood activity concentrations, scaled to therapeutic administered
      activities-both standard and myeloablative-were input into a geometry and
      tracking model (GEANT, version 4) of the aorta. The simulated energy deposited in
      the arterial walls was collected and fitted, and the AD and biologic effective
      dose values to the aortic wall and tumors were obtained for standard therapeutic
      and hypothetical myeloablative administered activities. RESULTS: Arterial wall
      ADs from standard therapy were lower (0.6-3.7 Gy) than those typical from
      external-beam therapy, as were the tumor ADs (1.4-10.5 Gy). The ratios of tumor
      AD to arterial wall AD were greater for radioimmunotherapy by a factor of 1.9
      4.0. For myeloablative therapy, artery wall ADs were in general less than those
      typical for external-beam therapy (9.4-11.4 Gy for 3 of 4 patients) but
      comparable for 1 patient (32.6 Gy). CONCLUSION: Blood vessel radiation dose can
      be estimated using the software package 3D-RD combined with GEANT modeling. The
      dosimetry analysis suggested that arterial wall toxicity is highly unlikely in
      standard dose radioimmunotherapy but should be considered a potential concern and
      limiting factor in myeloablative therapy.

PMID- 20150266
TI  - Comparison of initial cell retention and clearance kinetics after subendocardial
      or subepicardial injections of endothelial progenitor cells in a canine
      myocardial infarction model.
AB  - Neither intravenous nor intracoronary routes provide targeted stem cell delivery
      to recently infarcted myocardium in sufficient quantities. Direct routes appear
      preferable. However, most prior studies have used epicardial injections, which
      are not practical for routine clinical use. The objective of this study was to
      compare cell retention and clearance kinetics between a subepicardial and a
      subendocardial technique. METHODS: We evaluated 7 dogs with each technique, using
      (111)In-tropolone-labeled endothelial progenitor cells and serial SPECT/CT for 15
      d after injection. RESULTS: In vivo indium imaging demonstrated comparable
      degrees of retention: 57% +/- 15% for the subepicardial injections and 54% +/-
      26% for the subendocardial injections. Clearance half-lives were also similar at
      69 +/- 26 and 60 +/- 21 h, respectively. CONCLUSION: This study demonstrates that
      subendocardial injections, clinically more practical, show clearance kinetics
      comparable to those of subepicardial injections and will facilitate the ultimate
      clinical use of this treatment modality.

PMID- 20150267
TI  - Response of recurrent high-grade glioma to treatment with (90)Y-DOTATOC.
AB  - The treatment of patients with high-grade malignant glioma still represents an
      unsolved clinical problem. We report the treatment of 3 patients who had World
      Health Organization grade IV recurrent glioblastoma: a 23-y-old woman and 2 men
      aged 61 and 62 y. METHODS: All 3 patients were treated with the somatostatin
      receptor radiopharmaceutical (90)Y-labeled [1,4,7,10-tetraazacyclododecane
      N,N',N'',N'''-tetraacetic acid(0)-d-Phe(1),Tyr(3)]octreotide (DOTATOC). A
      cumulated dose of 1.7-2.2 GBq given in 3 or 4 cycles was locally injected into a
      previously implanted catheter system. RESULTS: Treatment was successful in all 3
      patients, with only minor side effects reported. After treatment, MRI and PET
      showed complete remission in one patient and partial remission in the other
      patients. These findings correlated well with clinical improvement and improved
      quality of life. CONCLUSION: Receptor-mediated radionuclide therapy by locally
      injected (90)Y-DOTATOC is feasible and well tolerated. This approach represents
      an attractive strategy for the treatment of locally recurring or progressing
      glioblastoma.

PMID- 20150269
TI  - Targeting prostate cancer cells in vivo using a rapidly internalizing novel human
      single-chain antibody fragment.
AB  - Human antibodies targeting prostate cancer cell surface epitopes may be useful
      for imaging and therapy. The objective of this study was to evaluate the tumor
      targeting of an internalizing human antibody fragment, a small-size platform, to
      provide high contrast in a mouse model of human prostate carcinoma. METHODS: A
      prostate tumor-targeting single-chain antibody fragment (scFv), UA20, along with
      a nonbinding control scFv, N3M2, were labeled with (99m)Tc and evaluated for
      binding and rapid internalization into human prostate tumor cells in vitro and
      tumor homing in vivo using xenograft models. For the in vitro studies, the
      labeled UA20 scFv was incubated at 37 degrees C for 1 h with metastatic prostate
      cancer cells (DU145) to assess the total cellular uptake versus intracellular
      uptake. For the animal studies, labeled UA20 and N3M2 scFvs were administered to
      athymic mice implanted subcutaneously with DU145 cells. Mice were imaged with
      small-animal SPECT/CT with concomitant biodistribution at 1 and 3 h after
      injection. RESULTS: The UA20 scFv was labeled in 55%-65% yield and remained
      stable in phosphate buffer within 24 h. The labeled UA20 scFv was taken up
      specifically by prostate tumor cells. Internalization was rapid, because
      incubation at 37 degrees C for less than 1 h resulted in 93% internalization of
      total cell-associated scFvs. In animal studies, SPECT/CT showed significant tumor
      uptake as early as 1 h after injection. At 3 h after injection, tumor uptake was
      4.4 percentage injected dose per gram (%ID/g), significantly greater than all
      organs or tissues studied (liver, 2.7 %ID/g; other organs or tissues, <1 %ID/g),
      except the kidneys (81.4 %ID/g), giving tumor-to-blood and tumor-to-muscle ratios
      of 12:1 and 70:1, respectively. In contrast, the control antibody exhibited a
      tumor uptake of only 0.26 %ID/g, similar to that of muscle and fat. Tumor
      specific targeting was evidenced by reduced tumor uptake of nearly 70% on
      administration of a 10-fold excess of unlabeled UA20 scFv. Kidney uptake was
      nonspecific, consistent with the route of excretion by scFvs. CONCLUSION: The
      UA20 scFv showed rapid and specific internalization in prostate tumor cells in
      vitro and accumulation in prostate tumor xenografts in vivo, demonstrating the
      potential for future development for prostate cancer imaging and targeted
      therapy.

PMID- 20150268
TI  - A novel facile method of labeling octreotide with (18)F-fluorine.
AB  - Several methods have been developed to label peptides with (18)F. However, in
      general these are laborious and require a multistep synthesis. We present a
      facile method based on the chelation of (18)F-aluminum fluoride (Al(18)F) by
      1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The method is characterized
      by the labeling of NOTA-octreotide (NOTA-d-Phe-cyclo[Cys-Phe-d-Trp-Lys-Thr-Cys]
      Throl (MH(+) 1305) [IMP466]) with (18)F. METHODS: Octreotide was conjugated with
      the NOTA chelate and labeled with (18)F in a 2-step, 1-pot method. The labeling
      procedure was optimized with regard to the labeling buffer, peptide, and aluminum
      concentration. Radiochemical yield, specific activity, in vitro stability, and
      receptor affinity were determined. Biodistribution of (18)F-IMP466 was studied in
      AR42J tumor-bearing mice and compared with that of (68)Ga-labeled IMP466. In
      addition, small-animal PET/CT images were acquired. RESULTS: IMP466 was labeled
      with Al(18)F in a single step with 50% yield. The labeled product was purified by
      high-performance liquid chromatography to remove unbound Al(18)F and unlabeled
      peptide. The radiolabeling, including purification, was performed in 45 min. The
      specific activity was 45,000 GBq/mmol, and the peptide was stable in serum for 4
      h at 37 degrees C. Labeling was performed at pH 4.1 in sodium citrate, sodium
      acetate, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, and 2-(N
      morpholino)ethanesulfonic acid buffer and was optimal in sodium acetate buffer.
      The apparent 50% inhibitory concentration of the (19)F-labeled IMP466 determined
      on AR42J cells was 3.6 nM. Biodistribution studies at 2 h after injection showed
      a high tumor uptake of (18)F-IMP466 (28.3 +/- 5.2 percentage injected dose per
      gram [%ID/g]; tumor-to-blood ratio, 300 +/- 90), which could be blocked by an
      excess of unlabeled peptide (8.6 +/- 0.7 %ID/g), indicating that the accumulation
      in the tumor was receptor-mediated. Biodistribution of (68)Ga-IMP466 was similar
      to that of (18)F-IMP466. (18)F-IMP466 was stable in vivo, because bone uptake was
      only 0.4 +/- 0.2 %ID/g, whereas free Al(18)F accumulated rapidly in the bone
      (36.9 +/- 5.0 %ID/g at 2 h after injection). Small-animal PET/CT scans showed
      excellent tumor delineation and high preferential accumulation in the tumor.
      CONCLUSION: NOTA-octreotide could be labeled rapidly and efficiently with (18)F
      using a 2-step, 1-pot method. The compound was stable in vivo and showed rapid
      accretion in somatostatin receptor subtype 2-expressing AR42J tumors in nude
      mice. This method can be used to label other NOTA-conjugated compounds with
      (18)F.

PMID- 20150272
TI  - Methotrexate, paclitaxel, and doxorubicin radiosensitize HER2-amplified human
      breast cancer cells to the Auger electron-emitting radiotherapeutic agent (111)In
      NLS-trastuzumab.
AB  - Our goal in this study was to elucidate the mechanisms by which methotrexate
      radiosensitizes HER2-positive human breast cancer cells to the Auger electron
      emitter (111)In-trastuzumab modified with nuclear-localization sequence peptides
      ((111)In-NLS-trastuzumab) and to compare these mechanisms with the potential
      sensitizing effects of paclitaxel and doxorubicin when combined with this
      radiopharmaceutical. METHODS: Experiments were performed in MDA-MB-231 human
      breast cancer cells, their HER2-transfected subclones (231-H2N), and 2
      trastuzumab-resistant variants (trastuzumab-resistant-1 and -2 [TrR1 and TrR2]).
      Effects of coexposure of these cells to (111)In-NLS-trastuzumab and low-dose,
      radiosensitizing methotrexate, paclitaxel, or doxorubicin were assessed by
      clonogenic cell-survival assay. Quantification of residual DNA damage was
      measured by the gammaH2AX-immunofluorescence assay, and cell cycle distribution
      was measured by fluorescence-activated cell sorting analysis. The radiation
      enhancement ratio was calculated as the ratio of the surviving fraction (SF) of
      cells treated with (111)In-NLS-trastuzumab alone to that of cells treated
      concurrently with (111)In-NLS-trastuzumab and methotrexate, paclitaxel, or
      doxorubicin. RESULTS: A reduction in the SF in HER2-positive 231-H2N (55.7% +/-
      1.3%) and TrR1 (62.6% +/- 6.5%) cells was demonstrated after exposure to (111)In
      NLS-trastuzumab (approximately 0.2 MBq/microg, 100 nmol/L) but not in MDA-MB-231
      or TrR2 cells expressing low levels of HER2 (SF > 90%, P > 0.05).
      Coadministration of methotrexate, paclitaxel, or doxorubicin enhanced the
      cytotoxicity of (111)In-NLS-trastuzumab toward 231-H2N and TrR1 cells but not
      toward MDA-MB-231 or TrR2 cells. The radiation-enhancement ratios for
      methotrexate, paclitaxel, and doxorubicin for 231-H2N or TrR1 cells were 2.0-2.2,
      1.6-1.8, and 2.7-2.8, respectively. Methotrexate or doxorubicin combined with
      (111)In-NLS-trastuzumab, compared to treatment with (111)In-NLS-trastuzumab
      alone, significantly increased residual gammaH2AX foci in 231-H2N and TrR1 cells
      but not in MDA-MB-231 or TrR2 cells or in any cell line treated concurrently with
      paclitaxel and (111)In-NLS-trastuzumab. Cells exposed to low-dose methotrexate
      accumulated in the G(1)/S phase of the cell cycle, whereas low-dose paclitaxel or
      doxorubicin caused cells to arrest in the G(2)/M phase. CONCLUSION: Low-dose
      methotrexate, paclitaxel, or doxorubicin potently sensitized HER2-overexpressing
      human breast cancer cells, with and without acquired trastuzumab-resistance, to
      the Auger electron emissions from (111)In-NLS-trastuzumab through cell cycle
      distribution changes and in part through the inhibitory effects of these agents
      on DNA damage repair.

PMID- 20150273
TI  - Influence of trigger PSA and PSA kinetics on (11)C-choline PET/CT detection rate
      in patients with biochemical relapse after radical prostatectomy.

PMID- 20150275
TI  - Diagnostic value of (18)F-FDG PET for evaluation of paraaortic nodal metastasis
      in patients with cervical carcinoma: a metaanalysis.
AB  - We assessed the diagnostic performance of (18)F-FDG PET in detecting paraaortic
      lymph node (PALN) metastasis in patients with cervical cancer. METHODS: Through a
      search of MEDLINE and EMBASE (1980 to March 2009), we performed a random-effects
      meta analysis. A summary receiver-operating-characteristic curve was constructed
      using hierarchical regression models. To identify other sources of heterogeneity,
      regression meta analysis was performed. RESULTS: Patients (n = 385) from 10
      studies were analyzed. Although specificity of (18)F-FDG PET was consistent (97%;
      95% confidence interval [CI], 93%-99%), sensitivity was low and heterogeneous
      among the studies (34%; 95% CI, 10%-72%). Although regression meta analysis did
      not identify any source to which heterogeneity could be attributed, it revealed a
      trend of increasing sensitivity according to an increase in the prevalence of
      PALN metastasis (P = 0.001). In the 5 studies with prevalence greater than 15%,
      estimated sensitivity and specificity were 73% (95% CI, 53%-87%) and 93% (95% CI,
      86%-97%), respectively. With the diagnostic performance, assuming the prevalence
      of 15%, the calculated false-positive and -negative rates were 35% and 5%,
      respectively. CONCLUSION: In detecting PALN metastasis, PET performs acceptably
      only in populations with a relatively high probability of PALN metastasis.
      Otherwise, we found no evidence to justify the evaluation of PALN based solely on
      PET in cervical cancer.

PMID- 20150276
TI  - The bHLH/PAS transcription factor singleminded 2s promotes mammary gland
      lactogenic differentiation.
AB  - We have previously demonstrated that the bHLH/PAS transcription factor,
      singleminded 2s (Sim2s), is required for proper mammary ductal morphogenesis and
      luminal epithelial differentiation. Furthermore, loss of Sim2s in breast cancer
      cells resulted in downregulation of epithelial markers and acquisition of a basal
      like phenotype. The objective of this study was to further define the role of
      Sim2s in mammary differentiation. We found that Sim2s is developmentally
      regulated throughout mammary gland development with highest expression during
      lactation. Mammary glands from nulliparous mice expressing Sim2s driven by the
      mouse mammary tumor virus (MMTV) long terminal repeat (LTR) promoter were
      morphologically indistinguishable from wild-type mice but displayed hallmarks of
      precocious lactogenic differentiation. These included elevated expression of the
      milk protein genes Wap and Csn2, and apical localization of the lactation marker
      Npt2b. Consistent with the in vivo results, Sim2s enhanced prolactin-mediated
      Csn2 expression in HC11 and CIT3 mouse mammary epithelial cells, and
      downregulation of Sim2s by shRNA in HC11 cells inhibited Csn2 expression.
      Chromatin immunoprecipitation (ChIP) analyses of the Csn2 gene found that Sim2s
      associates with the Csn2 promoter and re-ChIP experiments showed that Sim2s
      interacted with the RNA II polymerase (RNAPII) complex. Together, these data
      demonstrate, for the first time, that Sim2s is required for establishing and
      maintaining mammary gland differentiation.

PMID- 20150278
TI  - A conditional mutation in Arabidopsis thaliana separase induces chromosome non
      disjunction, aberrant morphogenesis and cyclin B1;1 stability.
AB  - The caspase family protease, separase, is required at anaphase onset to cleave
      the cohesin complex, which joins sister chromatids. However, among eukaryotes,
      separases have acquired novel functions. Here, we show that Arabidopsis thaliana
      radially swollen 4 (rsw4), a temperature-sensitive mutant isolated previously on
      the basis of root swelling, harbors a mutation in At4g22970, the A. thaliana
      separase. Loss of separase function in rsw4 at the restrictive temperature is
      indicated by the widespread failure of replicated chromosomes to disjoin.
      Surprisingly, rsw4 has neither pronounced cell cycle arrest nor anomalous spindle
      formation, which occur in other eukaryotes upon loss of separase activity.
      However, rsw4 roots have disorganized cortical microtubules and accumulate the
      mitosis-specific cyclin, cyclin B1;1, excessive levels of which have been
      associated with altered microtubules and morphology. Cyclin B1;1 also accumulates
      in certain backgrounds in response to DNA damage, but we find no evidence for
      aberrant responses to DNA damage in rsw4. Our characterization of rsw4 leads us
      to hypothesize that plant separase, in addition to cleaving cohesin, regulates
      cyclin B1;1, with profound ramifications for morphogenesis.

PMID- 20150277
TI  - The Trithorax group protein Ash2l and Saf-A are recruited to the inactive X
      chromosome at the onset of stable X inactivation.
AB  - Mammals compensate X chromosome gene dosage between the sexes by silencing of one
      of the two female X chromosomes. X inactivation is initiated in the early embryo
      and requires the non-coding Xist RNA, which encompasses the inactive X chromosome
      (Xi) and triggers its silencing. In differentiated cells, several factors
      including the histone variant macroH2A and the scaffold attachment factor SAF-A
      are recruited to the Xi and maintain its repression. Consequently, in female
      somatic cells the Xi remains stably silenced independently of Xist. Here, we
      identify the Trithorax group protein Ash2l as a novel component of the Xi. Ash2l
      is recruited by Xist concomitantly with Saf-A and macroH2A at the transition to
      Xi maintenance. Recruitment of these factors characterizes a developmental
      transition point for the chromatin composition of the Xi. Surprisingly,
      expression of a mutant Xist RNA that does not cause gene repression can trigger
      recruitment of Ash2l, Saf-A and macroH2A to the X chromosome, and can cause
      chromosome-wide histone H4 hypoacetylation. This suggests that a chromatin
      configuration is established on non-genic chromatin on the Xi by Xist to provide
      a repressive compartment that could be used for maintaining gene silencing. Gene
      silencing is mechanistically separable from the formation of this repressive
      compartment and, thus, requires additional pathways. This observation highlights
      a crucial role for spatial organization of chromatin changes in the maintenance
      of X inactivation.

PMID- 20150279
TI  - The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory
      neuron type via regulation of the ceh-36 Otx gene in C. elegans.
AB  - The differentiated features of postmitotic neurons are dictated by the expression
      of specific transcription factors. The mechanisms by which the precise
      spatiotemporal expression patterns of these factors are regulated are poorly
      understood. In C. elegans, the ceh-36 Otx homeobox gene is expressed in the AWC
      sensory neurons throughout postembryonic development, and regulates terminal
      differentiation of this neuronal subtype. Here, we show that the HMX/NKX
      homeodomain protein MLS-2 regulates ceh-36 expression specifically in the AWC
      neurons. Consequently, the AWC neurons fail to express neuron type-specific
      characteristics in mls-2 mutants. mls-2 is expressed transiently in postmitotic
      AWC neurons, and directly initiates ceh-36 expression. CEH-36 subsequently
      interacts with a distinct site in its cis-regulatory sequences to maintain its
      own expression, and also directly regulates the expression of AWC-specific
      terminal differentiation genes. We also show that MLS-2 acts in additional neuron
      types to regulate their development and differentiation. Our analysis describes a
      transcription factor cascade that defines the unique postmitotic characteristics
      of a sensory neuron subtype, and provides insights into the spatiotemporal
      regulatory mechanisms that generate functional diversity in the sensory nervous
      system.

PMID- 20150280
TI  - The cytolinker Pigs is a direct target and a negative regulator of Notch
      signalling.
AB  - Gas2-like proteins harbour putative binding sites for both the actin and the
      microtubule cytoskeleton and could thus mediate crosstalk between these
      cytoskeletal systems. Family members are highly conserved in all metazoans but
      their in vivo role is not clear. The sole Drosophila Gas2-like gene, CG3973
      (pigs), was recently identified as a transcriptional target of Notch signalling
      and might therefore link cell fate decisions through Notch activation directly to
      morphogenetic changes. We have generated a null mutant in CG3973 (pigs): pigs(1)
      mutants are semi-viable but adult flies are flightless, showing indirect flight
      muscle degeneration, and females are sterile, showing disrupted oogenesis and
      severe defects in follicle cell differentiation, similar to phenotypes seen when
      levels of Notch/Delta signalling are perturbed in these tissues. Loss of Pigs
      leads to an increase in Notch signalling activity in several tissues. These
      results indicate that Gas2-like proteins are essential for development and
      suggest that Pigs acts downstream of Notch as a morphogenetic read-out, and also
      as part of a regulatory feedback loop to relay back information about the
      morphogenetic state of cells to restrict Notch activation to appropriate levels
      in certain target tissues.

PMID- 20150281
TI  - Syntabulin, a motor protein linker, controls dorsal determination.
AB  - In amphibian and teleost embryos, the dorsal determinants (DDs) are believed to
      be initially localized to the vegetal pole and then transported to the
      prospective dorsal side of the embryo along a microtubule array. The DDs are
      known to activate the canonical Wnt pathway and thereby promote the expression of
      genes that induce the dorsal organizer. Here, by identifying the locus of the
      maternal-effect ventralized mutant tokkaebi, we show that Syntabulin, a linker of
      the kinesin I motor protein, is essential for dorsal determination in zebrafish.
      We found that syntabulin mRNA is transported to the vegetal pole during oogenesis
      through the Bucky ball (Buc)-mediated Balbiani body-dependent pathway, which is
      necessary for establishment of animal-vegetal (AV) oocyte polarity. We
      demonstrate that Syntabulin is translocated from the vegetal pole in a
      microtubule-dependent manner. Our findings suggest that Syntabulin regulates the
      microtubule-dependent transport of the DDs, and provide evidence for the link
      between AV and dorsoventral axis formation.

PMID- 20150282
TI  - Alterations in phosphorus, calcium and PTHrP contribute to defects in dental and
      dental alveolar bone formation in calcium-sensing receptor-deficient mice.
AB  - To determine whether the calcium-sensing receptor (CaR) participates in tooth
      formation and dental alveolar bone development in mandibles in vivo, we examined
      these processes, as well as mineralization, in 2-week-old CaR-knockout (CaR(-/-))
      mice. We also attempted to rescue the phenotype of CaR(-/-) mice by genetic
      means, in mice doubly homozygous for CaR and 25-hydroxyvitamin D 1alpha
      hydroxylase [1alpha(OH)ase] or parathyroid hormone (Pth). In CaR(-/-) mice, which
      exhibited hypercalcemia, hypophosphatemia and increased serum PTH, the volumes of
      teeth and of dental alveolar bone were decreased dramatically, whereas the ratio
      of the area of predentin to total dentin and the number and surface of
      osteoblasts in dental alveolar bone were increased significantly, as compared
      with wild-type littermates. The normocalcemia present in CaR(-/-);1alpha(OH)ase(
      /-) mice only slightly improved the defects in dental and alveolar bone formation
      observed in the hypercalcemic CaR(-/-) mice. However, these defects were
      completely rescued by the additional elimination of hypophosphatemia and by an
      increase in parathyroid hormone-related protein (PTHrP) expression in the apical
      pulp, Hertwig's epithelial root sheath and mandibular tissue in CaR(-/-); Pth(-/
      ) mice. Therefore, alterations in calcium, phosphorus and PTHrP contribute to
      defects in the formation of teeth and alveolar bone in CaR-deficient mice. This
      study indicates that CaR participates in the formation of teeth and in the
      development of dental alveolar bone in mandibles in vivo, although it appears to
      do so largely indirectly.

PMID- 20150283
TI  - Effect of prior intensive therapy in type 1 diabetes on 10-year progression of
      retinopathy in the DCCT/EDIC: comparison of adults and adolescents.
AB  - OBJECTIVE: The aim of this study was to examine differences between adolescents
      and adults in persistence of the benefits of intensive therapy 10 years after
      completion of the Diabetes Control and Complications Trial (DCCT). RESEARCH
      DESIGN AND METHODS: During the Epidemiology of Diabetes Interventions and
      Complications (EDIC) study, progression of retinopathy from DCCT closeout to EDIC
      year 10 was evaluated in 1,055 adults and 156 adolescents. RESULTS: During 10
      years of follow-up, HbA(1c) (A1C) was similar between original intensive (INT)
      and conventional (CON) groups and between former adolescents and adults. At EDIC
      year 10, adults in the former INT group continued to show slower progression of
      diabetic retinopathy than those in the CON group (adjusted hazard reduction 56%,
      P < 0.0001), whereas in adolescents this beneficial effect had disappeared (32%,
      P = 0.13). Seventy-nine percent of observed differences in the prolonged
      treatment effect between adults and adolescents at year 10 were explained by
      differences in mean A1C during DCCT between adolescents and adults (8.9 vs.
      8.1%), particularly between INT adolescents and adults (8.1 vs. 7.2%).
      CONCLUSIONS: Prior glycemic control during DCCT is vital for the persistence of
      the beneficial effects of INT therapy 10 years later. Lowering A1C to as close to
      normal as safely possible without severe hypoglycemia and starting as early as
      possible should be attempted for all subjects with type 1 diabetes. These results
      underscore the importance of maintaining A1C at target values for as long as
      possible because the benefits of former INT treatment wane over time if A1C
      levels rise.

PMID- 20150284
TI  - Vasoactive intestinal peptide-null mice demonstrate enhanced sweet taste
      preference, dysglycemia, and reduced taste bud leptin receptor expression.
AB  - OBJECTIVE: It is becoming apparent that there is a strong link between taste
      perception and energy homeostasis. Recent evidence implicates gut-related
      hormones in taste perception, including glucagon-like peptide 1 and vasoactive
      intestinal peptide (VIP). We used VIP knockout mice to investigate VIP's specific
      role in taste perception and connection to energy regulation. RESEARCH DESIGN AND
      METHODS: Body weight, food intake, and plasma levels of multiple energy
      regulating hormones were measured and pancreatic morphology was determined. In
      addition, the immunocytochemical profile of taste cells and gustatory behavior
      were examined in wild-type and VIP knockout mice. RESULTS: VIP knockout mice
      demonstrate elevated plasma glucose, insulin, and leptin levels, with no islet
      beta-cell number/topography alteration. VIP and its receptors (VPAC1, VPAC2) were
      identified in type II taste cells of the taste bud, and VIP knockout mice exhibit
      enhanced taste preference to sweet tastants. VIP knockout mouse taste cells show
      a significant decrease in leptin receptor expression and elevated expression of
      glucagon-like peptide 1, which may explain sweet taste preference of VIP knockout
      mice. CONCLUSIONS: This study suggests that the tongue can play a direct role in
      modulating energy intake to correct peripheral glycemic imbalances. In this way,
      we could view the tongue as a sensory mechanism that is bidirectionally regulated
      and thus forms a bridge between available foodstuffs and the intricate hormonal
      balance in the animal itself.

PMID- 20150285
TI  - Progression of diet-induced diabetes in C57BL6J mice involves functional
      dissociation of Ca2(+) channels from secretory vesicles.
AB  - OBJECTIVE: The aim of the study was to elucidate the cellular mechanism
      underlying the suppression of glucose-induced insulin secretion in mice fed a
      high-fat diet (HFD) for 15 weeks. RESEARCH DESIGN AND METHODS: C57BL6J mice were
      fed a HFD or a normal diet (ND) for 3 or 15 weeks. Plasma insulin and glucose
      levels in vivo were assessed by intraperitoneal glucose tolerance test. Insulin
      secretion in vitro was studied using static incubations and a perfused pancreas
      preparation. Membrane currents, electrical activity, and exocytosis were examined
      by patch-clamp technique measurements. Intracellular calcium concentration
      ([Ca(2+)](i)) was measured by microfluorimetry. Total internal reflection
      fluorescence microscope (TIRFM) was used for optical imaging of exocytosis and
      submembrane depolarization-evoked [Ca(2+)](i). The functional data were
      complemented by analyses of histology and gene transcription. RESULTS: After 15
      weeks, but not 3 weeks, mice on HFD exhibited hyperglycemia and hypoinsulinemia.
      Pancreatic islet content and beta-cell area increased 2- and 1.5-fold,
      respectively. These changes correlated with a 20-50% reduction of glucose-induced
      insulin secretion (normalized to insulin content). The latter effect was not
      associated with impaired electrical activity or [Ca(2+)](i) signaling. Single
      cell capacitance and TIRFM measurements of exocytosis revealed a selective
      suppression (>70%) of exocytosis elicited by short (50 ms) depolarization,
      whereas the responses to longer depolarizations were (500 ms) less affected. The
      loss of rapid exocytosis correlated with dispersion of Ca(2+) entry in HFD beta
      cells. No changes in gene transcription of key exocytotic protein were observed.
      CONCLUSIONS: HFD results in reduced insulin secretion by causing the functional
      dissociation of voltage-gated Ca(2+) entry from exocytosis. These observations
      suggest a novel explanation to the well-established link between obesity and
      diabetes.

PMID- 20150286
TI  - The glucagonostatic and insulinotropic effects of glucagon-like peptide 1
      contribute equally to its glucose-lowering action.
AB  - OBJECTIVE: Glucagon-like peptide 1 (GLP-1) exerts beneficial antidiabetic actions
      via effects on pancreatic beta- and alpha-cells. Previous studies have focused on
      the improvements in beta-cell function, while the inhibition of alpha-cell
      secretion has received less attention. The aim of this research was to quantify
      the glucagonostatic contribution to the glucose-lowering effect of GLP-1
      infusions in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Ten male
      patients with well-regulated type 2 diabetes (A1C 6.9 +/- 0.8%, age 56 +/- 10
      years, BMI 31 +/- 3 kg/m(2) [means +/- SD]) were subjected to five 120-min
      glucose clamps at fasting plasma glucose (FPG) levels. On day 1, GLP-1 was
      infused to stimulate endogenous insulin release and suppress endogenous glucagon.
      On days 2-5, pancreatic endocrine clamps were performed using somatostatin
      infusions of somatostatin and/or selective replacement of insulin and glucagon;
      day 2, GLP-1 plus basal insulin and glucagon (no glucagon suppression or insulin
      stimulation); day 3, basal insulin only (glucagon deficiency); day 4, basal
      glucagon and stimulated insulin; and day 5, stimulated insulin. The basal plasma
      glucagon levels were chosen to simulate portal glucagon levels. RESULTS: Peptide
      infusions produced the desired hormone levels. The amount of glucose required to
      clamp FPG was 24.5 +/- 4.1 (day 1), 0.3 +/- 0.2 (day 2), 10.6 +/- 1.1 (day 3),
      11.5 +/- 2.7 (day 4), and 24.5 +/- 2.6 g (day 5) (day 2 was lower than days 3 and
      4, which were both similar and lower than days 1 and 5). CONCLUSIONS: We
      concluded that insulin stimulation (day 4) and glucagon inhibition (day 3)
      contribute equally to the effect of GLP-1 on glucose turnover in patients with
      type 2 diabetes, and these changes explain the glucose-lowering effect of GLP-1
      (day 5 vs. day 1).

PMID- 20150287
TI  - Downregulation of adipose glutathione S-transferase A4 leads to increased protein
      carbonylation, oxidative stress, and mitochondrial dysfunction.
AB  - OBJECTIVE: Peripheral insulin resistance is linked to an increase in reactive
      oxygen species (ROS), leading in part to the production of reactive lipid
      aldehydes that modify the side chains of protein amino acids in a reaction termed
      protein carbonylation. The primary enzymatic method for lipid aldehyde
      detoxification is via glutathione S-transferase A4 (GSTA4) dependent
      glutathionylation. The objective of this study was to evaluate the expression of
      GSTA4 and the role(s) of protein carbonylation in adipocyte function. RESEARCH
      DESIGN AND METHODS: GSTA4-silenced 3T3-L1 adipocytes and GSTA4-null mice were
      evaluated for metabolic processes, mitochondrial function, and reactive oxygen
      species production. GSTA4 expression in human obesity was evaluated using
      microarray analysis. RESULTS: GSTA4 expression is selectively downregulated in
      adipose tissue of obese insulin-resistant C57BL/6J mice and in human obesity
      linked insulin resistance. Tumor necrosis factor-alpha treatment of 3T3-L1
      adipocytes decreased GSTA4 expression, and silencing GSTA4 mRNA in cultured
      adipocytes resulted in increased protein carbonylation, increased mitochondrial
      ROS, dysfunctional state 3 respiration, and altered glucose transport and
      lipolysis. Mitochondrial function in adipocytes of lean or obese GSTA4-null mice
      was significantly compromised compared with wild-type controls and was
      accompanied by an increase in superoxide anion. CONCLUSIONS: These results
      indicate that downregulation of GSTA4 in adipose tissue leads to increased
      protein carbonylation, ROS production, and mitochondrial dysfunction and may
      contribute to the development of insulin resistance and type 2 diabetes.

PMID- 20150288
TI  - Full-length adiponectin attenuates insulin signaling and inhibits insulin
      stimulated amino Acid transport in human primary trophoblast cells.
AB  - OBJECTIVE: Maternal adiponectin levels are reduced and placental nutrient
      transporters are upregulated in obesity and gestational diabetes mellitus;
      however, the effects of adiponectin on placental function are unknown. We
      hypothesized that adiponectin regulates placental amino acid transport. RESEARCH
      DESIGN AND METHODS: Human primary trophoblast cells were cultured and incubated
      with globular adiponectin (gAd) or full-length adiponectin (fAd) alone or in
      combination with insulin. System A and L amino acid transport and SNAT1, SNAT2,
      and SNAT4 isoform expression was measured. The activity of the AMP-activated
      protein kinase (AMPK), phosphatidylinositol 3 kinase-AKT, and peroxisome
      proliferator-activated receptor-alpha (PPARalpha) signaling pathways was
      determined. RESULTS: In the absence of insulin, gAd stimulated AMPK Thr172
      phosphorylation, SNAT2 protein expression, and system A activity. This effect
      appeared to be mediated by interleukin-6 release and signal transducer and
      activator of transcription 3 (STAT3) signaling because gAd failed to stimulate
      system A in cells in which STAT3 had been silenced using small interfering RNA.
      fAd alone had no effect on system A activity or SNAT expression. Insulin
      increased AKT and insulin receptor substrate 1 (IRS-1) phosphorylation, system A
      activity, and SNAT2 expression. When combined with insulin, gAd did not affect
      system A activity or SNAT expression. In contrast, fAd abolished insulin
      stimulated AKT Thr308 and IRS-1 Tyr612 phosphorylation, system A activity, and
      SNAT2 expression. Furthermore, fAd increased PPARalpha expression and PPARalpha
      (Ser21) phosphorylation. CONCLUSIONS: In contrast to the insulin-sensitizing
      actions of adiponectin in liver and muscle reported in the literature, fAd
      attenuates insulin signaling in primary human trophoblast cells. As a result, fAd
      inhibits insulin-stimulated amino acid transport, which may have important
      implications for placental nutrient transport and fetal growth in pregnancy
      complications associated with altered maternal adiponectin levels.

PMID- 20150289
TI  - Estimating visceral fat area by multifrequency bioelectrical impedance.
AB  - OBJECTIVE: We developed a new method of estimating visceral fat area (VFA) using
      multifrequency bioelectrical impedance (BI). RESEARCH DESIGN AND METHODS: We
      considered abdominal composition as a parallel circuit model composed of VFA and
      subcutaneous fat area and calculated the impedance of VFA (IP(VFA)) from this
      model. The methods were tested against measures of VFA by computed tomography
      (CT). Multiple regression analysis was performed on 103 participants to estimate
      VFA. We cross-validated the regression equation against CT-measured VFA in 30
      additional participants. RESULTS: The regression equation was VFA = 3.57 x
      sagittal abdominal diameter + 311.97 x waist-to-height ratio + 0.71 x age + 23.93
      x sex + 1.57 x IP(VFA) (250 kHz) - 174.35 (r = 0.904, P < 0.01). We observed a
      strong correlation by cross-validation (r = 0.905). CONCLUSIONS: Our method using
      BI is a simple and convenient method for accurately estimating VFA.

PMID- 20150290
TI  - Relationships between metabolic syndrome and other baseline factors and the
      efficacy of ezetimibe/simvastatin and atorvastatin in patients with type 2
      diabetes and hypercholesterolemia.
AB  - OBJECTIVE: To investigate relationships between baseline factors and treatment
      associated efficacy changes in type 2 diabetes. RESEARCH DESIGN: AND METHODS
      Multivariable analyses of treatment response in 1,229 type 2 diabetic patients
      with hypercholesterolemia who received ezetimibe/simvastatin or atorvastatin in a
      randomized double-blind 6-week study. RESULTS: Increasing age was related to
      improvements in all lipid assessments. Men had greater triglyceride and non-HDL
      cholesterol reductions than women, and black/Hispanic patients had less favorable
      lipid effects than other races/ethnicities. Increasing baseline LDL cholesterol
      was associated with improvements in most lipids; higher baseline non-HDL
      cholesterol with improved HDL cholesterol and triglycerides; higher baseline HDL
      cholesterol with greater non-HDL cholesterol and high-sensitivity C-reactive
      protein (hs-CRP) reductions; and higher baseline hs-CRP with smaller LDL
      cholesterol, non-HDL cholesterol, and apolipoprotein B reductions. Patients with
      high baseline non-HDL cholesterol or triglycerides less frequently attained LDL
      cholesterol targets. Obesity was inversely related to HDL cholesterol and hs-CRP
      changes, and higher baseline A1C to smaller apolipoprotein B reductions.
      Metabolic syndrome was not a significant predictor. CONCLUSIONS: Treatment
      responses in type 2 diabetic patients were related to baseline factors, although
      treatment effects (ezetimibe/simvastatin being more effective than atorvastatin)
      remained consistent. The presence of predictive factors should be considered in
      planning lipid-altering therapy.

PMID- 20150291
TI  - The relationship between diabetes distress and clinical depression with glycemic
      control among patients with type 2 diabetes.
AB  - OBJECTIVE: To clarify previous findings that diabetes distress is related to
      glycemic control and self-management whereas measures of depression are not,
      using both binary and continuous measures of depression. RESEARCH DESIGN AND
      METHODS: Four hundred and sixty-three type 2 patients completed measures of
      diabetes distress (Diabetes Distress Scale [DDS]) and clinical depression
      (Patient Health Questionnaire 8 [PHQ8]). PHQ8 was employed as either a binary
      (>or=10) or continuous variable. Dependent variables were A1C, diet, physical
      activity (PA), and medication adherence (MA). RESULTS: The inclusion of a binary
      or continuous PHQ8 score yielded no differences in any equation. DDS was
      significantly associated with A1C and PA, whereas PHQ8 was not; both DDS and PHQ8
      were significantly and independently associated with diet and MA. CONCLUSIONS:
      The lack of association between depression and glycemic control is not due to the
      use of a binary measure of depression. Findings further clarify the significant
      association between distress and A1C.

PMID- 20150292
TI  - MD-logic artificial pancreas system: a pilot study in adults with type 1
      diabetes.
AB  - OBJECTIVE: Current state-of-the-art artificial pancreas systems are either based
      on traditional linear control theory or rely on mathematical models of glucose
      insulin dynamics. Blood glucose control using these methods is limited due to the
      complexity of the biological system. The aim of this study was to describe the
      principles and clinical performance of the novel MD-Logic Artificial Pancreas
      (MDLAP) System. RESEARCH DESIGN AND METHODS: The MDLAP applies fuzzy logic theory
      to imitate lines of reasoning of diabetes caregivers. It uses a combination of
      control-to-range and control-to-target strategies to automatically regulate
      individual glucose levels. Feasibility clinical studies were conducted in seven
      adults with type 1 diabetes (aged 19-30 years, mean diabetes duration 10 +/- 4
      years, mean A1C 6.6 +/- 0.7%). All underwent 14 full, closed-loop control
      sessions of 8 h (fasting and meal challenge conditions) and 24 h. RESULTS: The
      mean peak postprandial (overall sessions) glucose level was 224 +/- 22 mg/dl.
      Postprandial glucose levels returned to <180 mg/dl within 2.6 +/- 0.6 h and
      remained stable in the normal range for at least 1 h. During 24-h closed-loop
      control, 73% of the sensor values ranged between 70 and 180 mg/dl, 27% were >180
      mg/dl, and none were <70 mg/dl. There were no events of symptomatic hypoglycemia
      during any of the trials. CONCLUSIONS: The MDLAP system is a promising tool for
      individualized glucose control in patients with type 1 diabetes. It is designed
      to minimize high glucose peaks while preventing hypoglycemia. Further studies are
      planned in the broad population under daily-life conditions.

PMID- 20150293
TI  - A high-protein diet with resistance exercise training improves weight loss and
      body composition in overweight and obese patients with type 2 diabetes.
AB  - OBJECTIVE To evaluate the effects of two low-fat hypocaloric diets differing in
      the carbohydrate-to-protein ratio, with and without resistance exercise training
      (RT), on weight loss, body composition, and cardiovascular disease (CVD) risk
      outcomes in overweight/obese patients with type 2 diabetes. RESEARCH DESIGN AND
      METHODS A total of 83 men and women with type 2 diabetes (aged 56.1 +/- 7.5
      years, BMI 35.4 +/- 4.6 kg/m(2)) were randomly assigned to an isocaloric, energy
      restricted diet (female subjects 6 MJ/day, male subjects 7 MJ/day) of either
      standard carbohydrate (CON; carbohydrate:protein:fat 53:19:26) or high protein
      (HP; 43:33:22), with or without supervised RT (3 days/week) for 16 weeks. Body
      weight and composition, waist circumference (WC), and cardiometabolic risk
      markers were assessed. RESULTS Fifty-nine participants completed the study. There
      was a significant group effect (P <or= 0.04) for body weight, fat mass, and WC
      with the greatest reductions occurring in HP+RT (weight [CON: -8.6 +/- 4.6 kg,
      HP: -9.0 +/- 4.8 kg, CON+RT: -10.5 +/- 5.1 kg, HP+RT: -13.8 +/- 6.0 kg], fat mass
      [CON: -6.4 +/- 3.4 kg, HP: -6.7 +/- 4.0 kg, CON+RT: -7.9 +/- 3.7 kg, HP+RT: -11.1
      +/- 3.7 kg], and WC [CON: -8.2 +/- 4.6 cm, HP: -8.9 +/- 3.9 cm, CON+RT: -11.3 +/-
      4.6 cm, HP+RT: -13.7 +/- 4.6 cm]). There was an overall reduction (P < 0.001) in
      fat-free mass (-2.0 +/- 2.3 kg), blood pressure (-15/8 +/- 10/6 mmHg), glucose (
      2.1 +/- 2.2 mmol/l), insulin (-4.7 +/- 5.4 mU/l), A1C (-1.25 +/- 0.94%),
      triglycerides (-0.47 +/- 0.81 mmol/l), total cholesterol (-0.67 +/- 0.69 mmol/l),
      and LDL cholesterol (-0.37 +/- 0.53 mmol/l), with no difference between groups (P
      >or= 0.17). CONCLUSIONS An energy-restricted HP diet combined with RT achieved
      greater weight loss and more favorable changes in body composition. All
      treatments had similar improvements in glycemic control and CVD risk markers.

PMID- 20150294
TI  - Pioglitazone decreases plasma cholesteryl ester transfer protein mass, associated
      with a decrease in hepatic triglyceride content, in patients with type 2
      diabetes.
AB  - OBJECTIVE: Thiazolidinediones reduce hepatic steatosis and increase HDL
      cholesterol levels. In mice with human-like lipoprotein metabolism (APOE*3
      Leiden.CETP transgenic mice), a decrease in hepatic triglyceride content is
      associated with a decrease in plasma cholesteryl ester transfer protein (CETP)
      mass and an increase in HDL levels. Therefore, the aim of the present study was
      to assess the effects of pioglitazone on CETP mass in patients with type 2
      diabetes. RESEARCH DESIGN AND METHODS: We included 78 men with type 2 diabetes
      (aged 56.5 +/- 0.6 years; HbA1c 7.1 +/- 0.1%) who were randomly assigned to
      treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day) and matching
      placebo, in addition to glimepiride. At baseline and after 24 weeks of treatment
      plasma HDL cholesterol levels and CETP mass were measured, and hepatic
      triglyceride content was assessed by proton magnetic resonance spectroscopy.
      RESULTS Pioglitazone decreased hepatic triglyceride content (5.9 [interquartile
      range 2.6-17.4] versus 4.1 [1.9-12.3]%, P < 0.05), decreased plasma CETP mass
      (2.33 +/- 0.10 vs. 2.06 +/- 0.10 microg/ml, P < 0.05), and increased plasma HDL
      cholesterol level (1.22 +/- 0.05 vs. 1.34 +/- 0.05 mmol/l, P < 0.05). Metformin
      did not significantly change any of these parameters. CONCLUSIONS: A decrease in
      hepatic triglyceride content by pioglitazone is accompanied by a decrease in
      plasma CETP mass and associated with an increase in HDL cholesterol levels. These
      results in patients with type 2 diabetes fully confirm recent findings in mice.

PMID- 20150295
TI  - Time course and mechanisms of circulating progenitor cell reduction in the
      natural history of type 2 diabetes.
AB  - OBJECTIVE: Reduction of bone marrow-derived circulating progenitor cells has been
      proposed as a novel mechanism of cardiovascular disease in type 2 diabetes. The
      present study was designed to describe the extent and potential mechanisms of
      progenitor cell reduction during the natural history of type 2 diabetes. RESEARCH
      DESIGN AND METHODS: We identified 425 individuals, divided into seven categories
      according to carbohydrate metabolism status (normal glucose tolerance [NGT],
      impaired fasting glucose, impaired glucose tolerance [IGT], and newly diagnosed
      type 2 diabetes) and diabetes duration (0-9, 10-19, and >or=20 years). These
      categories were examined as ideally describing the natural history of type 2
      diabetes development and progression. We measured CD34+ and CD34+KDR+ progenitor
      cells by flow cytometry. We also evaluated progenitor cells in 20 coupled bone
      marrow and peripheral blood samples and examined progenitor cell apoptosis in 34
      subjects. RESULTS: In comparison to NGT, CD34+ cells were significantly reduced
      in IGT and had a first nadir in newly diagnosed type 2 diabetes and a second
      nadir after 20 years of diabetes. Statistical adjustment for possible confounders
      confirmed that CD34+ cell counts are deeply reduced at time of diagnosis, that
      they partially recover during the subsequent 0-19 years, and that they dip again
      after >or=20 years. A similar, but less consistent, trend was detected for
      CD34+KDR+ cells. Peripheral blood CD34+ cells were directly correlated with bone
      marrow CD34+ cells and inversely correlated with CD34+ cell apoptosis.
      CONCLUSIONS: Circulating progenitor cell reduction marks the clinical onset of
      type 2 diabetes. Both defective mobilization and increased apoptosis may account
      for this phenomenon. While a partial recovery occurs during subsequent years,
      bone marrow reserve seems exhausted in the long term.

PMID- 20150296
TI  - Moisture status of the skin of the feet assessed by the visual test neuropad
      correlates with foot ulceration in diabetes.
AB  - OBJECTIVE: To examine the association between the moisture status of the skin of
      the feet with foot ulceration in subjects with diabetes. RESEARCH DESIGN AND
      METHODS: A total of 379 subjects with diabetes were examined. Assessment of
      peripheral neuropathy was based on neuropathy symptom score, neuropathy
      disability score, vibration perception threshold, and the 10-g monofilament
      perception. The moisture status of the skin of the feet was assessed using the
      visual test Neuropad. RESULTS: Patients with foot ulceration had more severe
      peripheral neuropathy and more often an abnormal Neuropad response. Multivariate
      logistic regression analysis demonstrated that the odds of foot ulceration
      increased with measures of neuropathy but increased also with an abnormal
      Neuropad response. CONCLUSIONS: An abnormal Neuropad response correlates with
      foot ulceration in subjects with diabetes. This finding, if confirmed
      prospectively, suggests that the Neuropad test may be included in the screening
      tests for the prediction of foot ulceration.

PMID- 20150297
TI  - Effect of prior intensive insulin treatment during the Diabetes Control and
      Complications Trial (DCCT) on peripheral neuropathy in type 1 diabetes during the
      Epidemiology of Diabetes Interventions and Complications (EDIC) Study.
AB  - OBJECTIVE: To evaluate the impact of former intensive versus conventional insulin
      treatment on neuropathy in Diabetes Control and Complications Trial (DCCT)
      intensive and conventional treatment subjects with type 1 diabetes 13-14 years
      after DCCT closeout, during which time the two groups had achieved similar A1C
      levels. RESEARCH DESIGN AND METHODS: Clinical and nerve conduction studies (NCSs)
      performed during the DCCT were repeated during the Epidemiology of Diabetes
      Interventions and Complications (EDIC) study by examiners masked to treatment
      status on 603 former intensive and 583 former conventional treatment subjects.
      Clinical neuropathy was defined by symptoms, sensory signs, or reflex changes
      consistent with distal polyneuropathy and confirmed with NCS abnormalities
      involving two or more nerves among the median, peroneal, and sural nerves.
      RESULTS: The prevalence of neuropathy increased 13-14 years after DCCT closeout
      from 9 to 25% in former intensive and from 17 to 35% in former conventional
      treatment groups, but the difference between groups remained significant (P <
      0.001), and the incidence of neuropathy remained lower among former intensive
      (22%) than former conventional (28%) treatment subjects (P = 0.0125). Analytic
      models of incident neuropathy that adjusted for differences in NCS results at
      DCCT closeout showed no significant risk reduction associated with former
      intensive treatment during follow-up (odds ratio 1.17 [95% CI 0.84-1.63]).
      However, a significant persistent treatment group effect was observed for several
      NCS measures. Longitudinal analyses of overall glycemic control showed a
      significant association between mean A1C and measures of incident and prevalent
      neuropathy. CONCLUSIONS: The benefits of former intensive insulin treatment
      persisted for 13-14 years after DCCT closeout and provide evidence of a durable
      effect of prior intensive treatment on neuropathy.

PMID- 20150298
TI  - An association between subclinical hypothyroidism and sight-threatening diabetic
      retinopathy in type 2 diabetic patients.
AB  - OBJECTIVE: To determine the relationship between subclinical hypothyroidism (SCH)
      and the prevalence of diabetic retinopathy in type 2 diabetic patients. RESEARCH
      DESIGN AND METHODS: A total of 1,170 type 2 diabetic patients were screened for
      thyroid function. There were 127 type 2 diabetic patients with SCH and 200
      randomly selected euthyroid type 2 diabetic patients selected. Those with more
      severe than moderate nonproliferative diabetic retinopathy were classified as
      having sight-threatening diabetic retinopathy (STDR). RESULTS: The trend for
      severe retinopathy was significantly higher in the SCH group than in the
      euthyroid group (chi(2) = 20.43, P = 0.000). SCH was associated with greater
      prevalence of diabetic retinopathy, especially STDR [odds ratio (95% CI): 4.15
      (2.17-7.96), P = 0.000] after an adjustment for age, sex, duration of diabetes,
      A1C, BMI, hypertension, and LDL cholesterol. Even euthyroid patients with thyroid
      stimulating hormone levels between 2.0 and <4.0 microIU/ml had a higher rate of
      STDR then those between 0.4 and <2.0 microIU/ml (P = 0.008). CONCLUSIONS: Type 2
      diabetic patients with SCH are associated with an increased risk of STDR.

PMID- 20150299
TI  - Self-efficacy, problem solving, and social-environmental support are associated
      with diabetes self-management behaviors.
AB  - OBJECTIVE: To evaluate associations between psychosocial and social-environmental
      variables and diabetes self-management, and diabetes control. RESEARCH DESIGN AND
      METHODS: Baseline data from a type 2 diabetes self-management randomized trial
      with 463 adults having elevated BMI (M = 34.8 kg/m(2)) were used to investigate
      relations among demographic, psychosocial, and social-environmental variables;
      dietary, exercise, and medication-taking behaviors; and biologic outcomes.
      RESULTS: Self-efficacy, problem solving, and social-environmental support were
      independently associated with diet and exercise, increasing the variance
      accounted for by 23 and 19%, respectively. Only diet contributed to explained
      variance in BMI (beta = -0.17, P = 0.0003) and self-rated health status (beta =
      0.25, P < 0.0001); and only medication-taking behaviors contributed to lipid
      ratio (total-to-HDL) (beta = -0.20, P = 0.0001) and A1C (beta = -0.21, P <
      0.0001). CONCLUSIONS: Interventions should focus on enhancing self-efficacy,
      problem solving, and social-environmental support to improve self-management of
      diabetes.

PMID- 20150300
TI  - Effect of treatment of gestational diabetes mellitus on obesity in the next
      generation.
AB  - OBJECTIVE: Gestational diabetes mellitus (GDM) may cause obesity in the
      offspring. The objective was to assess the effect of treatment for mild GDM on
      the BMI of 4- to 5-year-old children. RESEARCH DESIGN AND METHODS: Participants
      were 199 mothers who participated in a randomized controlled trial of the
      treatment of mild GDM during pregnancy and their children. Trained nurses
      measured the height and weight of the children at preschool visits in a state
      wide surveillance program in the state of South Australia. The main outcome
      measure was age- and sex-specific BMI Z score based on standards of the
      International Obesity Task Force. RESULTS: At birth, prevalence of macrosomia
      (birth weight >or=4,000 g) was 5.3% among the 94 children whose mothers were in
      the intervention group, and 21.9% among the 105 children in the routine care
      control group. At 4- to 5-years-old, mean (SD) BMI Z score was 0.49 (1.20) in
      intervention children and 0.41 (1.40) among controls. The difference between
      treatment groups was 0.08 (95% CI -0.29 to 0.44), an estimate minimally changed
      by adjustment for maternal race, parity, age, and socio-economic index (0.08 [
      0.29 to 0.45]). Evaluating BMI >or=85th percentile rather than continuous BMI Z
      score gave similarly null results. CONCLUSIONS: Although treatment of GDM
      substantially reduced macrosomia at birth, it did not result in a change in BMI
      at age 4- to 5-years-old.

PMID- 20150301
TI  - Neighborhood socioeconomic change and diabetes risk: findings from the Chicago
      childhood diabetes registry.
AB  - OBJECTIVE: To examine whether patterns in socioeconomic characteristics in
      Chicago over a 30-year period are associated with neighborhood distribution of
      youth diabetes risk. RESEARCH DESIGN AND METHODS: Incident cases of diabetes in
      youth aged 0-17 years were identified from the Chicago Childhood Diabetes
      Registry between 1994 and 2003. Those with a type 2 diabetes-like clinical course
      or related indicators were classified as non-type 1 diabetic; the remaining cases
      were considered to have type 1 diabetes. RESULTS: Compared with stable diversity
      neighborhoods, significant associations for type 1 diabetes were found for
      younger children residing in emerging low-income neighborhoods (relative risk
      0.56 [95% CI 0.36-0.90]) and older children residing in emerging high-income
      neighborhoods (1.52 [1.17-1.98]). For non-type 1 diabetes, older youth residing
      in desertification neighborhoods were at increased risk (1.47 [1.09-1.99]).
      CONCLUSIONS: Neighborhood socioeconomic characteristics in Chicago may be
      associated with the risk of diabetes in youth.

PMID- 20150302
TI  - Early pharmacokinetic and pharmacodynamic effects of mixing lispro with glargine
      insulin: results of glucose clamp studies in youth with type 1 diabetes.
AB  - OBJECTIVE Clinicians who treat children with type 1 diabetes often try to
      minimize the number of daily injections to reduce treatment burden and improve
      compliance. Despite the manufacturer's cautions against mixing glargine with
      rapid-acting insulin analogs, clinical studies have failed to demonstrate
      deleterious effects of mixing on glucose excursions or A1C levels. However, no
      formal glucose clamp studies have been performed to determine whether mixing with
      glargine has an adverse effect on the early pharmacodynamic action of rapid
      acting insulin in humans. RESEARCH DESIGN AND METHODS To examine this question,
      euglycemic glucose clamps were performed twice, in random order, in 11 youth with
      type 1 diabetes (age 15.1 +/- 3 years, A1C 7.6 +/- 0.6%) with 0.2 units/kg lispro
      and 0.4 units/kg glargine, given either as separate or as a single mixed
      injection. RESULTS Mixing the two insulins shifted the time action curve to the
      right, with significantly lower glucose infusion rate (GIR) values after the
      mixed injections between 60 and 190 min and significantly higher values between
      270 and 300 min, lowered the GIR(max) (separate 7.1 +/- 1 vs. mix 3.9 +/- 1, P =
      0.03), and markedly delayed the time to reach GIR(max) (separate 116 +/- 8 min
      vs. mix 209 +/- 15 min, P = 0.004). The GIR area under the curve was
      significantly lower after the mixed injections. Mixing had similar effects on
      plasma insulin pharmacokinetics. CONCLUSIONS These data demonstrate that mixing
      lispro with glargine markedly flattens the early pharmacodynamic peak of lispro
      and causes a shift to the right in the GIR curve changes that might lead to
      difficulties in controlling meal-related glucose excursions.

PMID- 20150303
TI  - The efficacy of endovascular stenting in the treatment of supraclinoid internal
      carotid artery blister aneurysms using a stent-in-stent technique.
AB  - BACKGROUND AND PURPOSE: Blister aneurysms of the supraclinoid ICA represent a
      rare but well-documented cause of subarachnoid hemorrhage. These aneurysms are
      difficult to detect, and their surgical treatment is challenging, with high
      morbidity and mortality rates. The reports currently in the literature that
      describe the surgical and endovascular treatment of these aneurysms offer no
      clear consensus on the optimal treatment. We describe a staged endovascular
      treatment entailing stenting using a stent-in-stent technique, as well as planned
      but delayed embolization as the aneurysm increases in size to allow the
      introduction of coils. MATERIALS AND METHODS: We performed a retrospective review
      of all cerebral angiograms performed at our institution over an 8-month period
      for evaluation of subarachnoid hemorrhage, identifying 6 ICA blister aneurysms.
      RESULTS: All 6 blister aneurysms were located in the supraclinoid ICA. The stent
      in-stent technique was used for the initial treatment of all patients. Three
      patients had no residual or recurrent aneurysm following initial treatment. Three
      patients required retreatment with coils after continued growth of the aneurysm,
      identified on follow-up angiography. Five patients had good recovery (average mRS
      score of 1), and 1 patient had poor neurologic recovery (mRS score of 3) due to a
      large hemorrhagic infarction. CONCLUSIONS: Our case series suggests that staged
      endovascular treatment entailing the use of a stent-in-stent technique, augmented
      with subsequent coil embolization as necessary for progressive disease, is a
      viable endovascular option for treating ruptured supraclinoid blister aneurysms,
      allowing for parent artery preservation.

PMID- 20150304
TI  - Treatment of intracranial aneurysms by functional reconstruction of the parent
      artery: the Budapest experience with the pipeline embolization device.
AB  - BACKGROUND AND PURPOSE: Aneurysm treatment by intrasaccular packing has been
      associated with a relatively high rate of recurrence. The use of mesh tubes has
      recently gained traction as an alternative therapy. This article summarizes the
      midterm results of using an endoluminal sleeve, the PED, in the treatment of
      aneurysms. MATERIALS AND METHODS: A total of 19 wide-neck aneurysms were treated
      in 18 patients: 10 by implantation of PEDs alone and 9 by a combination of PED
      and coils. Angiographic and clinical results were recorded immediately and at 6
      months following treatment. RESULTS: Immediate angiographic occlusion was
      achieved in 4 and flow reduction, in another 15 aneurysms. Angiography at 6
      months demonstrated complete occlusion in 17 and partial filling in 1 of 18
      patients. There was no difference between coil-packed and unpacked aneurysms. Of
      28 side branches covered by > or =1 device, the ophthalmic artery was absent
      immediately in 1 and at 6 months in another 2 cases. One patient experienced
      abrupt in-stent thrombosis resulting in a transient neurologic deficit, and 1
      patient died due to rupture of a coexisting aneurysm. All giant aneurysms treated
      with PED alone were demonstrated by follow-up cross-sectional imaging to have
      involuted by 6 months. CONCLUSIONS: Treatment of large, wide-neck, or otherwise
      untreatable aneurysms with functional reconstruction of the parent artery may be
      achieved with relative safety using dedicated flow-modifying devices with or
      without adjunctive use of intrasaccular coil packing.

PMID- 20150305
TI  - Onset and progression of pathologic atrophy in Huntington disease: a longitudinal
      MR imaging study.
AB  - BACKGROUND AND PURPOSE: Longitudinal MR imaging measures provide an opportunity
      to track progression in HD before the emergence of clinical symptoms. This may
      prove useful in assessing disease-modifying treatments. We investigated how
      caudate and global volumes change as HD progresses from premanifest to early
      disease. MATERIALS AND METHODS: Forty HD gene-positive individuals and 19
      controls underwent serial volumetric MR imaging (baseline, 12 and 27 months; 2 or
      3 scans per person). At baseline, 3 patients with HD were premanifest but
      developed overt motor features during the study, and 37 had early HD. All had
      dates of motor onset recorded. Caudates, lateral ventricles, and TIVs were
      measured using semiautomated procedures. Linear mixed models were used to
      investigate differences between HD and controls in relation to motor onset,
      controlling for TIV, sex, and age. RESULTS: Extrapolating backwards in time, we
      found that differences in caudate and ventricular volumes between patients with
      HD and controls were evident 14 and 5 years, respectively, before motor onset (P
      < .05). At onset, caudate volume was 2.58 mL smaller than that in controls (P <
      .0001); ventricular volume was 9.27 mL larger (P < .0001). HD caudate atrophy
      rates were linear, showed low variability between subjects, and were
      approximately 10-fold higher than those in controls (P < .001). HD ventricular
      enlargement rates were variable between subjects, were approximately 4-fold
      higher than those in controls at onset (P < .001), and accelerated with disease
      duration (P = .02). CONCLUSIONS: We provide evidence of acceleration of global
      atrophy in HD with disproportionate caudate involvement. Both caudate and global
      measures may be of use as early markers of HD pathology.

PMID- 20150306
TI  - MR spectroscopy detects lipid peaks in cerebrotendinous xanthomatosis.
AB  - CTX is a rare lipid-storage disease. Novel MRS findings from 3 patients, using a
      short TE, were the presence of lipid peaks at 0.9 and 1.3 ppm in the depth of the
      cerebellar hemisphere; this might represent an additional marker of disease that
      is CNS-specific and noninvasive. A decrease in NAA concentration was also
      detected and attributed to neuroaxonal damage. One patient presented an increase
      in mIns concentration, pointing to gliosis and astrocytic proliferation.

PMID- 20150307
TI  - Apparent diffusion coefficient of glial neoplasms: correlation with
      fluorodeoxyglucose-positron-emission tomography and gadolinium-enhanced MR
      imaging.
AB  - BACKGROUND AND PURPOSE: Gd-enhancement provides essential information in the
      assessment of brain tumors. However, enhancement does not always correlate with
      histology or disease activity, especially in the setting of current therapies.
      Our aim was to compare FDG-PET scans to ADC maps and Gd-enhanced MR images in
      patients with glial neoplasms to assess whether DWI might offer information not
      available on routine MR imaging sequences and whether such findings have
      prognostic significance. MATERIALS AND METHODS: Institutional review board
      approval was obtained for this retrospective review, which was conducted in full
      compliance with HIPAA regulations. Twenty-one patients (11 men and 10 women) with
      glial tumors underwent FDG-PET and MR imaging, including ADC and Gd- enhancement.
      Subjectively, regions of interest were drawn around the following areas: 1)
      increased FDG uptake, 2) decreased signal intensity on ADC maps, and 3) Gd
      enhancement. Objectively, FDG-PET and MR images were co-registered, and pixel-by
      pixel comparison of ADC to PET values was made for all regions of interest.
      Correlation coefficients (r values) were calculated for each region of interest.
      Percentage overlap between regions of interest was calculated for each case.
      RESULTS: Subjective evaluation showed 60% of patients with excellent or good
      correlation between ADC maps and FDG-PET. Pixel-by-pixel comparison demonstrated
      r values that ranged from -0.72 to -0.21. There was significantly greater overlap
      between decreased ADC and increased FDG-PET uptake (67.1 +/- 15.5%) versus
      overlap between Gd-enhancement and increased FDG-PET uptake (54.4 +/- 27.5%) (P <
      .05). ADC overlap was greater with increased FDG-PET than with Gd-enhancement in
      8/9 cases. Survival data revealed that the presence of restricted diffusion on
      ADC correlated with patient survival (P < .0001). CONCLUSIONS: ADC maps in
      patients with brain tumors provide unique information that is analogous to FDG
      PET. There is a greater overlap between ADC and FDG-PET compared with Gd
      enhancement. ADC maps can serve to approximate tumor grade and predict survival.

PMID- 20150308
TI  - Direct percutaneous venous puncture and embolization of giant perimedullary
      arteriovenous fistulas.
AB  - PMAVFs are rare entities that are formed by a direct communication between an
      artery that feeds the spinal cord and a vein. The goal of treatment is to occlude
      the shunt; this is done endovascularly either from an arterial or a venous
      approach. When these approaches are not possible, direct percutaneous puncture of
      the draining veins may be attempted to embolize the arteriovenous shunt directly.

PMID- 20150309
TI  - MR imaging in novel influenza A(H1N1)-associated meningoencephalitis.
AB  - MR imaging manifestations of influenza A-associated encephalitis have been
      described previously. However, there is very limited information about the
      central nervous system complications of the novel influenza A(H1N1) virus. MR
      imaging findings of novel influenza A-associated meningoencephalitis in a child
      are presented.

PMID- 20150311
TI  - Perforator infarction after placement of a pipeline flow-diverting stent for an
      unruptured A1 aneurysm.

PMID- 20150310
TI  - Comparison of the risk of oculomotor nerve deficits between detachable balloons
      and coils in the treatment of direct carotid cavernous fistulas.
AB  - BACKGROUND AND PURPOSE: Transarterial balloon embolization used to be the
      preferred method for treating DCCFs; however, a strayed, overinflated, or
      migrated balloon may lead to oculomotor palsy. This investigation compared the
      use of detachable balloons and GDCs, which were previously used only in cases of
      balloon-technique failure and are now increasingly used as a first-line treatment
      for DCCFs, in terms of the risk of oculomotor nerve deficit, mortality/morbidity,
      and initial angiographic results. MATERIALS AND METHODS: Among 48 patients with
      DCCFs treated with endovascular embolization at our institution between March
      2004 and May 2009, 38 patients were included in this review. Patients who
      underwent trapping procedures, a second intervention within 2 weeks, or any
      procedure that included n-BCA infusion were excluded. Twenty of the enrolled
      patients were treated with transarterial balloons and the other 18, with GDCs.
      RESULTS: Five patients (25%) in the balloon group and none in the coil group had
      oculomotor nerve deficits within 2 weeks. The rate of procedure-related
      oculomotor nerve deficit was significantly higher in the balloon group than in
      the coil group (P = .048). There were no significant differences in terms of
      procedure-related mortality/morbidity or initial angiographic results between the
      2 groups. CONCLUSIONS: The risk of procedure-related oculomotor nerve deficit in
      the treatment of DCCFs was significantly lower when using a GDC than with a
      detachable balloon. GDCs may, therefore, be considered as feasible, effective,
      and safe for DCCFs as detachable balloons.

PMID- 20150312
TI  - Blood-flow characteristics in a terminal basilar tip aneurysm prior to its fatal
      rupture.
AB  - BACKGROUND AND PURPOSE: The development and validation of methods to stratify the
      risk of rupture of cerebral aneurysms is highly desired because current treatment
      risks can exceed the natural risk of rupture. Because unruptured aneurysms are
      typically treated before they rupture, it is very difficult to connect the
      proposed risk indices to the rupture of an individual aneurysm. The purpose of
      this case study was to analyze the hemodynamic environment of a saccular aneurysm
      of the terminal morphology subtype that was imaged just before its rupture and to
      test whether the hemodynamic characteristics would designate this particular
      aneurysm as at high risk. MATERIALS AND METHODS: A patient-specific CFD model was
      constructed from 3DRA images acquired just hours before the aneurysm ruptured. A
      pulsatile flow calculation was performed, and hemodynamic characteristics
      previously connected to rupture were analyzed. RESULTS: It was found that the
      aneurysm had a concentrated inflow stream, small impingement region, complex
      intra-aneurysmal flow structure, asymmetric flow split from the parent vessel to
      the aneurysm and daughter branches, and high levels of aneurysmal WSS near the
      impaction zone. CONCLUSIONS: The hemodynamic characteristics observed in this
      aneurysm right before its rupture are consistent with previous studies
      correlating aneurysm rupture and hemodynamic patterns in saccular and terminal
      aneurysms. This study supports the notion that hemodynamic information may be
      used to help stratify the rupture risk of cerebral aneurysms.

PMID- 20150313
TI  - Programmable CSF shunt valves: radiographic identification and interpretation.
AB  - The programmable CSF shunt valve has become an important tool in hydrocephalus
      treatment, particularly in the NPH population and in pediatric patients with
      complex hydrocephalus. The purpose of this study is to provide a single reference
      for the identification of programmable shunt valves and the interpretation of
      programmable shunt valve settings. Four major manufacturers of programmable
      shunts agreed to participate in this study. Each provided radiographic images and
      legends for their appropriate interpretation. Issues of MR imaging compatibility
      for each valve are also discussed.

PMID- 20150316
TI  - The evolution of clinical functional imaging during the past 2 decades and its
      current impact on neurosurgical planning.
AB  - BOLD fMRI has, during the past decade, made a major transition from a purely
      research imaging technique to a viable clinical technique used primarily for
      presurgical planning in patients with brain tumors and other resectable brain
      lesions. This review article briefly examines the history and evolution of
      clinical functional imaging, with particular emphasis on how the use of BOLD fMRI
      for neurosurgical planning has changed during the past 2 decades. Even more
      important, this article describes the many published studies during that same
      period that have examined the overall clinical impact that BOLD and DTI have made
      on surgical planning.

PMID- 20150317
TI  - Genotypic detection and molecular epidemiology of extended-spectrum beta
      lactamase-producing Escherichia coli and Klebsiella pneumoniae in a regional
      hospital in central Taiwan.
AB  - This study was conducted to detect the genes encoding extended-spectrum beta
      lactamases (ESBLs) and determine the epidemiological relatedness of 69
      Escherichia coli and 33 Klebsiella pneumoniae isolates collected from a regional
      hospital in central Taiwan, mostly from inpatients (E. coli 87.0%; K. pneumoniae
      88.0%). The phenotypes of these isolates were examined according to the
      combination disc method recommended by the Clinical and Laboratory Standards
      Institute. Most of the ESBL-producing E. coli and K. pneumoniae isolates (98.6%
      and 97%, respectively) could be detected using cefotaxime discs with and without
      clavulanate. Genotyping was performed by PCR with type-specific primers. CTX-M-14
      type (53.6%) was the most prevalent ESBL among E. coli isolates while SHV type
      (57.6%) was the most dominant among K. pneumoniae isolates. Six E. coli and three
      K. pneumoniae isolates did not carry genes encoding ESBLs of types TEM, SHV, CTX
      M-3, CTX-M-14, CMY-2 and DHA-1. The co-existence of two or more kinds of ESBL in
      a single isolate was common, occurring in 40.6% and 72.7% of E. coli and K.
      pneumoniae isolates, respectively. PFGE analysis revealed that ESBL producers
      isolated in this setting were genetically divergent.

PMID- 20150318
TI  - Characterization of the gastrointestinal yeast microbiota of cockatiels
      (Nymphicus hollandicus): a potential hazard to human health.
AB  - Cockatiels are the world's second most popular psittacine pet bird, but no data
      characterizing their gastrointestinal microbiota have been found. Thus, the aim
      of this work was to characterize the yeast gastrointestinal microbiota of
      cockatiels and to evaluate the relevance of cockatiels as carriers of potentially
      pathogenic yeasts. A total of 60 cockatiels, from 15 different premises, were
      assessed. A thorough clinical examination was performed with each bird, and
      samples were collected from oral cavity, crop and cloaca. The stools were
      collected from cages where the birds were kept. The isolates were identified
      according to morphological and biochemical characteristics. Yeasts were isolated
      from at least one anatomical site of 65% of the birds and 64.3% of the stool
      samples. The oral cavity (53.3%) and the crop (58.3%) were the anatomical sites
      with the highest prevalence and the highest number of yeast isolates. Overall,
      120 yeast isolates, belonging to 13 species, were obtained. The most frequently
      isolated species were Candida albicans, with 39 (32.5%) isolates, followed by
      Candida tropicalis (20%), Trichosporon asteroides (12.5%), Candida famata (10%)
      and others. Mixed yeast colonies were isolated from 23.3% of the birds and C.
      albicans was seldom found in association with other species (P<0.05). The results
      of this work demonstrated that cockatiels harbour potentially pathogenic yeasts
      throughout their gastrointestinal tract and in stools, and are prone to
      disseminating them in the environment.

PMID- 20150319
TI  - Real-time quantitative PCR in cerebral toxoplasmosis diagnosis of Brazilian human
      immunodeficiency virus-infected patients.
AB  - Cerebral toxoplasmosis is the most common cerebral mass lesion in AIDS patients
      in Brazil, and results in high mortality and morbidity, despite free access to
      HAART (highly active antiretroviral treatment). Molecular diagnosis based on
      conventional PCR (cnPCR) or real-time quantitative PCR (qrtPCR) has been
      indispensable for definitive diagnosis. We report here the evaluation of qrtPCR
      with blood and cerebrospinal fluid (CSF) samples from AIDS patients in Brazil.
      This prospective study was conducted for 2 years, analysing DNA samples extracted
      from 149 AIDS patients (98 blood and 51 CSF samples) with confirmed clinical and
      radiological diagnosis. The laboratory diagnosis included cnPCR (with the B22/B23
      primer set) and indirect immunofluorescence (IF). For qrtPCR, two primer sets
      were simultaneously designed based on described genes and using a 6
      carboxyfluorescein dye-labelled TaqMan MGB (minor groove binder) probe. One was
      B1Tg, which amplified a sequence from the B1 gene. The other was the RETg, which
      amplified a PCR product of the 529 bp sequence. The overall cnPCR and qrtPCR
      results were: positive results were observed in 33.6% (50) patients. The
      sensitivities were 98% for cnPCR (B22/B23), and 86 and 98% for qrtPCR (B1Tg and
      RETg, respectively). Negative reactions were observed in 66.4% patients. The
      specificities were 97% for cnPCR and qrtPCR (B1Tg), and 88.8 % for RETg. These
      data show that RETg PCR is highly sensitive as it amplifies a repeat region with
      many copies; however, its specificity is lower than the other markers. However,
      B1Tg PCR had good specificity, but lower sensitivity. Among the patients, 20 had
      blood and CSF collected simultaneously. Thus, their results permitted us to
      analyse and compare molecular, serological and clinical diagnosis for a better
      understanding of the different scenarios of laboratorial and clinical diagnosis.
      For nine patients with confirmed cerebral toxoplasmosis diagnosis, four scenarios
      were observed: (i) and (ii) negative molecular diagnosis for CSF and positive for
      blood with variable IF titres for the sera and CSF (negative or positive); (iii)
      positive molecular diagnosis with CSF and negative with blood; and (iv) positive
      molecular diagnosis in both samples. In the latter two situations, normally the
      IF titres in sera and CSF are variable. Other opportunistic infections were shown
      in 11 patients. Despite the IF titres in sera and CSF being variable, all of them
      had negative molecular diagnosis for both samples. qrtPCR allows for a rapid
      identification of Toxoplasma gondii DNA in patient samples; in a minority of
      cases discrepancies occur with the cnPCR.

PMID- 20150320
TI  - Accurate detection and genotyping of SNPs utilizing population sequencing data.
AB  - Next-generation sequencing technologies have made it possible to sequence
      targeted regions of the human genome in hundreds of individuals. Deep sequencing
      represents a powerful approach for the discovery of the complete spectrum of DNA
      sequence variants in functionally important genomic intervals. Current methods
      for single nucleotide polymorphism (SNP) detection are designed to detect SNPs
      from single individual sequence data sets. Here, we describe a novel method SNIP
      Seq (single nucleotide polymorphism identification from population sequence data)
      that leverages sequence data from a population of individuals to detect SNPs and
      assign genotypes to individuals. To evaluate our method, we utilized sequence
      data from a 200-kilobase (kb) region on chromosome 9p21 of the human genome. This
      region was sequenced in 48 individuals (five sequenced in duplicate) using the
      Illumina GA platform. Using this data set, we demonstrate that our method is
      highly accurate for detecting variants and can filter out false SNPs that are
      attributable to sequencing errors. The concordance of sequencing-based genotype
      assignments between duplicate samples was 98.8%. The 200-kb region was
      independently sequenced to a high depth of coverage using two sequence pools
      containing the 48 individuals. Many of the novel SNPs identified by SNIP-Seq from
      the individual sequencing were validated by the pooled sequencing data and were
      subsequently confirmed by Sanger sequencing. We estimate that SNIP-Seq achieves a
      low false-positive rate of approximately 2%, improving upon the higher false
      positive rate for existing methods that do not utilize population sequence data.
      Collectively, these results suggest that analysis of population sequencing data
      is a powerful approach for the accurate detection of SNPs and the assignment of
      genotypes to individual samples.

PMID- 20150321
TI  - Fast and efficient searching of biological data resources--using EB-eye.
AB  - The EB-eye is a fast and efficient search engine that provides easy and uniform
      access to the biological data resources hosted at the EMBL-EBI. Currently, users
      can access information from more than 62 distinct datasets covering some 400
      million entries. The data resources represented in the EB-eye include: nucleotide
      and protein sequences at both the genomic and proteomic levels, structures
      ranging from chemicals to macro-molecular complexes, gene-expression experiments,
      binary level molecular interactions as well as reaction maps and pathway models,
      functional classifications, biological ontologies, and comprehensive literature
      libraries covering the biomedical sciences and related intellectual property. The
      EB-eye can be accessed over the web or programmatically using a SOAP Web Services
      interface. This allows its search and retrieval capabilities to be exploited in
      workflows and analytical pipe-lines. The EB-eye is a novel alternative to
      existing biological search and retrieval engines. In this article we describe in
      detail how to exploit its powerful capabilities.

PMID- 20150322
TI  - RNA-targeted splice-correction therapy for neuromuscular disease.
AB  - Splice-modulation therapy, whereby molecular manipulation of premessenger RNA
      splicing is engineered to yield genetic correction, is a promising novel therapy
      for genetic diseases of muscle and nerve-the prototypical example being Duchenne
      muscular dystrophy. Duchenne muscular dystrophy is the most common childhood
      genetic disease, affecting one in 3500 newborn boys, causing progressive muscle
      weakness, heart and respiratory failure and premature death. No cure exists for
      this disease and a number of promising new molecular therapies are being
      intensively studied. Duchenne muscular dystrophy arises due to mutations that
      disrupt the open-reading-frame in the DMD gene leading to the absence of the
      essential muscle protein dystrophin. Of all novel molecular interventions
      currently being investigated for Duchenne muscular dystrophy, perhaps the most
      promising method aiming to restore dystrophin expression to diseased cells is
      known as 'exon skipping' or splice-modulation, whereby antisense oligonucleotides
      eliminate the deleterious effects of DMD mutations by modulating dystrophin pre
      messenger RNA splicing, such that functional dystrophin protein is produced.
      Recently this method was shown to be promising and safe in clinical trials both
      in The Netherlands and the UK. These trials studied direct antisense
      oligonucleotide injections into single peripheral lower limb muscles, whereas a
      viable therapy will need antisense oligonucleotides to be delivered systemically
      to all muscles, most critically to the heart, and ultimately to all other
      affected tissues including brain. There has also been considerable progress in
      understanding how such splice-correction methods could be applied to the
      treatment of related neuromuscular diseases, including spinal muscular atrophy
      and myotonic dystrophy, where defects of splicing or alternative splicing are
      closely related to the disease mechanism.

PMID- 20150323
TI  - Which antithrombotic to use during PCI?

PMID- 20150324
TI  - Bivalirudin vs. unfractionated heparin during percutaneous coronary interventions
      in patients with stable and unstable angina pectoris: 1-year results of the ISAR
      REACT 3 trial.
AB  - AIMS: In ISAR-REACT 3, 30-day outcomes in 4570 biomarker negative patients
      undergoing percutaneous coronary intervention (PCI) > or =2 h after pre-treatment
      with 600 mg of clopidogrel revealed less bleeding with bivalirudin compared with
      unfractionated heparin, but no difference in 30-day net clinical benefit. The
      objective of the present analysis was to assess the impact of bivalirudin vs.
      heparin on 1-year outcomes in ISAR-REACT 3. METHODS AND RESULTS: The primary
      outcome for this analysis was the composite of death, myocardial infarction, or
      target vessel revascularization 1 year after randomization. The composite of
      death or myocardial infarction was a secondary outcome. At 1 year, the primary
      outcome occurred in 17.1% of patients assigned to bivalirudin vs. 17.5% assigned
      to heparin [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.86-1.13; P =
      0.816]. The combined incidence of death or myocardial infarction was 7.7% in the
      bivalirudin group vs. 6.7% in the heparin group (HR, 1.15; 95% CI, 0.93-1.43; P =
      0.200). The mortality rate was 1.9% in the bivalirudin group and 1.7% in the
      heparin group (HR, 1.10; 95% CI, 0.71-1.70; P = 0.667). At 1 year, no significant
      differences in the primary outcome were observed with bivalirudin and heparin in
      any of the subgroups analysed. CONCLUSION: Bivalirudin and unfractionated heparin
      during PCI provide comparable outcomes at 1 year in biomarker negative patients
      undergoing PCI after pre-treatment with 600 mg of clopidogrel. CLINICAL TRIAL
      REGISTRATION INFORMATION: URL www.clinicaltrials.gov; Unique identifier
      NCT00262054.

PMID- 20150325
TI  - Endocrine treatment of transsexual persons: an Endocrine Society Clinical
      Practice Guideline: commentary from a European perspective.
AB  - The treatment of transsexual subjects is a challenging task for the
      endocrinologist who, in collaboration with the mental health professional and the
      surgeon, is called upon to confirm the diagnosis and adjust hormonal treatment
      aimed at suppressing endogenous sex hormones and to develop hormone
      characteristics of the desired gender. These guidelines are structured to provide
      evidence-based suggestions or, where evidence is lacking, expert recommendations
      on diagnostic procedures and hormonal treatment in adolescent and adult
      transsexuals, including long-term care and eligibility for surgery. The
      multidisciplinary approach to treatment, the additional diagnostic role of
      hormone administration and the need to maintain hormone levels within the
      physiological range are key suggestions stressed in the guidelines which are
      particularly important for an endocrinologist unfamiliar with this field. The
      need for psychological assessment before surgery is not common in many countries
      and should be stressed further in the guidelines. Some important issues such as
      time and method of hormone withdrawal before surgery together with when and which
      hormones should be administered after sex reassignment surgery has been completed
      also remain unclear. These guidelines represent a pivotal document for
      endocrinologists setting a standard for the care of transsexuals and providing
      directions for future research.

PMID- 20150326
TI  - Specificity and spatial dynamics of protein kinase A signaling organized by A
      kinase-anchoring proteins.
AB  - Protein phosphorylation is the most common post-translational modification
      observed in cell signaling and is controlled by the balance between protein
      kinase and phosphatase activities. The cAMP-protein kinase A (PKA) pathway is one
      of the most studied and well-known signal pathways. To maintain a high level of
      specificity, the cAMP-PKA pathway is tightly regulated in space and time. A
      kinase-anchoring proteins (AKAPs) target PKA to specific substrates and distinct
      subcellular compartments providing spatial and temporal specificity in the
      mediation of biological effects controlled by the cAMP-PKA pathway. AKAPs also
      serve as scaffolding proteins that assemble PKA together with signal terminators
      such as phosphoprotein phosphatases and cAMP-specific phosphodiesterases as well
      as components of other signaling pathways into multiprotein-signaling complexes.

PMID- 20150327
TI  - The puzzling uniqueness of the heterotrimeric G15 protein and its potential
      beyond hematopoiesis.
AB  - Heterotrimeric G proteins transduce the signals of the largest family of membrane
      receptors (G protein-coupled receptors, GPCRs) hence triggering the activation of
      a wide variety of physiological responses. G15 is a G protein characterized by a
      number of functional peculiarities that make its signaling exceptional: 1) it can
      couple a variety of Gs-, Gi/o-, and Gq-linked receptors to phospholipase C
      activation; 2) relatively to other G proteins, it is poorly affected by beta
      arrestin-dependent desensitization, the general mechanism that regulates GPCR
      function and 3) at the protein level, its expression is only detected in highly
      specific cell types (hematopoietic and epithelial cells). G15 alpha-subunit
      displays unique structural and biochemical properties, and is phylogenetically
      the most recent and divergent component of the Galphaq/11 subfamily. All these
      aspects shed a mysterious light on G15 biological role, which remains
      substantially elusive. Thus, far, G15 signaling has been analyzed in the context
      of hematopoiesis. Here, we highlight observations supporting the view that G15
      functions may extend further beyond the immune system. In addition, we describe
      puzzling aspects of G15 signaling that offer a novel perspective in the
      understanding of its physiological role.

PMID- 20150328
TI  - Cardiac resynchronization therapy may benefit patients with left ventricular
      ejection fraction >35%: a PROSPECT trial substudy.
AB  - AIMS: Cardiac resynchronization therapy (CRT) is currently limited to those with
      left ventricular ejection fraction (LVEF) < or =35%. To evaluate whether patients
      with LVEF >35% might benefit from CRT, we performed a retrospective analysis of
      the predictors of response to CRT (PROSPECT) database. METHODS AND RESULTS:
      PROSPECT was a prospective, multicentre study that enrolled CRT patients based on
      enrolling centre-evaluated LVEF <35%, but all echocardiograms were subsequently
      analysed by a core laboratory. Patients with core laboratory-measured LVEF >35%
      (OVER35) were compared with those whose LVEF was <35% (UNDER35). Clinical
      composite score (CCS) and change in LV end systolic volume (LVESV) were analysed
      from baseline to 6-month follow-up. Of 361 patients, 86 (24%) had LVEF >35%. At
      entry, OVER35 had smaller LV volumes, shorter QRS duration, shorter 6-min walk
      distance, and were more likely to have ischaemic aetiology than UNDER35. Outcomes
      were comparable between the groups, with 62.8% of OVER35 improved in CCS (70.2%
      in UNDER35) and 50.8% of OVER35 improved in LVESV (57.8% in UNDER35). CONCLUSION:
      Patients with LVEF >35%, New York heart association functional Class III-IV
      status, and QRS >130 ms appear to derive clinical and structural benefit from
      CRT. As CRT may offer a valuable option for these patients, this hypothesis
      should be formally tested in a prospective, randomized multicentre trial.

PMID- 20150329
TI  - Cardiac resynchronization therapy with individualized placement of two left
      ventricular leads at the sites of latest mechanical left ventricular contraction:
      guided by 3D-echocardiography and coronary sinus rotation angiography.
AB  - A 78-year-old woman with dilated cardiomyopathy was admitted for advanced
      dyspnoea and recurrent cardiac decompensation despite optimal medical therapy.
      Implantation of a cardiac resynchronization therapy (CRT) device was indicated
      according to current guidelines. The day before CRT implantation, three
      dimensional echocardiography was performed together with coronary sinus (CS)
      rotation angiography, which identified two sites of latest mechanical left
      ventricular (LV) contraction with adjacently available target veins. This case
      presents the first description of CRT target vein selection using a combination
      of functional information on LV contraction with anatomical information on the CS
      venous tree. In this specific patient, the approach eventually necessitated
      placement of two LV leads.

PMID- 20150331
TI  - Looking back on a decade of hospital policy research.

PMID- 20150332
TI  - Rediscovering a grandmother's breastfeeding technique: the pinky maneuver.

PMID- 20150330
TI  - Role of miR-34c microRNA in the late steps of spermatogenesis.
AB  - Spermatogenesis is a cyclic process in which diploid spermatogonia differentiate
      into haploid spermatozoa. This process is highly regulated, notably at the post
      transcriptional level. MicroRNAs (miRNAs), single-stranded noncoding RNA
      molecules of about 20-25 nucleotides, are implicated in the regulation of many
      important biological pathways such as proliferation, apoptosis, and
      differentiation. We wondered whether miRNAs could play a role during
      spermatogenesis. The miRNA expression repertoire was tested in germ cells, and we
      present data showing that miR-34c was highly expressed only in these cells.
      Furthermore, our findings indicate that in male gonads, miR-34c expression is
      largely p53 independent in contrast to previous results showing a direct link in
      somatic cells between the miR-34 family and this tumor suppressor protein. In
      order to identify target genes involved in germinal lineage differentiation, we
      overexpressed miR-34c in HeLa cells, analyzed the transcriptome of these modified
      cells, and noticed a shift of the expression profile toward the germinal lineage.
      Recently, it has been shown that exogenous expression of Ddx4/Vasa in embryonic
      chicken stem cells (cESC) induces cESC reprogramming toward a germ cell fate.
      When we simultaneously expressed miR-34c in such cells, we could detect an up
      regulation of germ cell-specific genes whereas the expression of other lineage
      specific markers remained unchanged. These data suggest that miR-34c could play a
      role by enhancing the germinal phenotype of cells already committed to this
      lineage.

PMID- 20150333
TI  - Collecting every drop.

PMID- 20150334
TI  - What do we mean when we talk about intrinsic and extrinsic motivation to
      breastfeed?: a commentary.

PMID- 20150336
TI  - Exploring breastfeeding ambivalence among low-income, minority women.

PMID- 20150338
TI  - Course and predictors of posttraumatic stress disorder in parents after pediatric
      intensive care treatment of their child.
AB  - OBJECTIVE: To study posttraumatic stress disorder (PTSD) in parents after
      unexpected pediatric intensive care unit (PICU) treatment of their child and to
      identify risk factors for its development. METHOD: Parents completed PTSD
      questionnaires 3 and 9 months (N = 190) after PICU treatment. Risk factors
      included pretrauma data, medical data, social demographics and posttraumatic
      stress responses at 3 months. RESULTS: In total, 30.3% of parents met criteria
      for subclinical PTSD and 12.6% for clinical PTSD at 3 months. Clinical PTSD
      prevalence rates did not change over time. At 9 months, 10.5% of parents still
      met criteria for PTSD. Number of earlier stressful life events, earlier
      psychosocial care and posttraumatic stress responses at 3 months predicted
      persistent subclinical and clinical PTSD. CONCLUSIONS: PICU admission is a
      stressful event associated with persistent parental PTSD. Assessment of risk
      factors can facilitate detection of persistent PTSD for early intervention.

PMID- 20150337
TI  - Characterization and analysis of carbon fibre-reinforced polymer composite
      laminates with embedded circular vasculature.
AB  - A study of the influence of embedded circular hollow vascules on structural
      performance of a fibre-reinforced polymer (FRP) composite laminate is presented.
      Incorporating such vascules will lead to multi-functional composites by bestowing
      functions such as self-healing and active thermal management. However, the
      presence of off-axis vascules leads to localized disruption to the fibre
      architecture, i.e. resin-rich pockets, which are regarded as internal defects and
      may cause stress concentrations within the structure. Engineering approaches for
      creating these simple vascule geometries in conventional FRP laminates are
      proposed and demonstrated. This study includes development of a manufacturing
      method for forming vascules, microscopic characterization of their effect on the
      laminate, finite element (FE) analysis of crack initiation and failure under
      load, and validation of the FE results via mechanical testing observed using high
      speed photography. The failure behaviour predicted by FE modelling is in good
      agreement with experimental results. The reduction in compressive strength owing
      to the embedding of circular vascules ranges from 13 to 70 per cent, which
      correlates with vascule dimension.

PMID- 20150339
TI  - Associations of ethnicity and SES with IQ and achievement in spina bifida
      meningomyelocele.
AB  - OBJECTIVES: We evaluated whether the phenotypic pattern of higher verbal than
      nonverbal IQ in children with spina bifida meningomyelocele (SBM) is consistent
      across subgroups differing in ethnicity and SES. We also explored the relation of
      cognitive and academic performance. METHODS: Non-Hispanic White (n = 153) and
      Hispanic (n = 80) children with SBM received the Stanford Binet Test of
      Intelligence-IV and achievement subtests of the Woodcock-Johnson. Parents
      completed questionnaires assessing the family environment [socioeconomic status
      (SES), resources, and educational opportunities]. RESULTS: Multivariate analysis
      revealed that Hispanic children with lower SES had lower verbal than nonverbal
      scores. Hispanic children with higher SES and non-Hispanic White children
      demonstrated the reverse pattern. Verbal and nonverbal IQ interacted to predict
      reading and math performance. CONCLUSIONS: Lower SES is associated with lower
      verbal IQ in economically disadvantaged Hispanic children with SBM. Academic
      achievement is largely correlated with verbal IQ, but children with lower verbal
      IQ may partially compensate with higher nonverbal ability.

PMID- 20150340
TI  - On the utility of short intron sequences as a reference for the detection of
      positive and negative selection in Drosophila.
AB  - The detection of selection, both positive and negative, acting on a DNA sequence
      or class of nucleotide sites requires comparison with a reference sequence that
      is unaffected by selection. In Drosophila, recent findings of widespread
      selective constraint, as well as adaptive evolution, in both coding and noncoding
      regions highlight the difficulties in choosing such a reference sequence. Here,
      we investigate the utility of short intron sequences as a reference for the
      detection of selection. For a set of 119 Drosophila melanogaster genes containing
      195 short introns (<or=120 bp), we analyzed polymorphism and divergence at 1) 4
      fold synonymous sites, 2) all sites of introns <or=120 bp, 3) all sites of
      introns <or=65 bp, 4) bases 8-30 of introns <or=120 bp, and 5) bases 8-30 of
      introns <or=65 bp. The last class of sites shows the highest levels of both
      interspecific divergence and intraspecific polymorphism, suggesting that these
      sites are under the least selective constraint. Bases 8-30 of introns <or=65 bp
      also have the lowest ratio of divergence to polymorphism, which may indicate that
      a small proportion of substitutions in the other classes of sites are the result
      of adaptive evolution. Although there is little signal of selection on the
      primary sequence of short introns, patterns of insertion-deletion polymorphism
      and divergence suggest that both positive and negative selection act to maintain
      an optimal intron length.

PMID- 20150341
TI  - Amygdala volume correlates positively with fearfulness in normal healthy girls.
AB  - Research into the neural underpinnings of fear and fear-related pathology has
      highlighted the role of the amygdala. For instance, bilateral damage to the
      amygdaloid complex is associated with decreased appreciation of danger and
      recognition of fear in humans, whereas enlarged amygdala volume is associated
      with internalizing syndromes. It is unknown whether amygdala volume and
      fearfulness are related in the absence of pathology. We examined the correlation
      between normal fearfulness and amygdala morphology in 116 healthy children and
      adolescents (60 boys, 56 girls, age 7-17 years). Fearfulness was measured using
      the parent ratings on the Pediatric Behavior Scale and amygdala volumes were
      determined by manual tracing. We found a positive correlation between right
      amygdala volume in girls (r = 0.29). This relationship was more robust and
      present bilaterally when analyses were limited to girls with a positive nuclear
      family history of depression (for left r = 0.63; for right r = 0.58). In boys
      there was no significant relationship which may suggest that biological
      mechanisms differ between sexes. Given the role of enlarged amygdala volume in
      pathology, these findings may indicate that variation in amygdala morphology
      marks susceptibility to internalizing disorders.

PMID- 20150342
TI  - On the wrong side of the trolley track: neural correlates of relative social
      valuation.
AB  - Using moral dilemmas, we (i) investigate whether stereotypes motivate people to
      value ingroup lives over outgroup lives and (ii) examine the neurobiological
      correlates of relative social valuation using fMRI. Saving ingroup members, who
      seem warm and competent (e.g. Americans), was most morally acceptable in the
      context of a dilemma where one person was killed to save five people. Extreme
      outgroup members, who seem neither warm nor competent (e.g. homeless), were the
      worst off; it was most morally acceptable to sacrifice them and least acceptable
      to save them. Sacrificing these low-warmth, low-competence targets to save
      ingroup targets, specifically, activated a neural network associated with
      resolving complex tradeoffs: medial PFC (BA 9, extending caudally to include
      ACC), left lateral OFC (BA 47) and left dorsolateral PFC (BA 10). These brain
      regions were recruited for dilemmas that participants ultimately rated as
      relatively more acceptable. We propose that participants, though ambivalent,
      overrode general aversion to these tradeoffs when the cost of sacrificing a low
      warmth, low-competence target was pitted against the benefit of saving ingroup
      targets. Moral decisions are not made in a vacuum; intergroup biases and
      stereotypes weigh heavily on neural systems implicated in moral decision making.

PMID- 20150345
TI  - Recommendations on perioperative beta-blockers: differing guidelines: so what
      should the clinician do?

PMID- 20150343
TI  - The neural substrates of action identification.
AB  - Mentalization is the process by which an observer views a target as possessing
      higher cognitive faculties such as goals, intentions and desires. Mentalization
      can be assessed using action identification paradigms, in which observers choose
      mentalistic (goals-focused) or mechanistic (action-focused) descriptions of
      targets' actions. Neural structures that play key roles in inferring goals and
      intentions from others' observed or imagined actions include temporo-parietal
      junction, ventral premotor cortex and extrastriate body area. We hypothesized
      that these regions play a role in action identification as well. Data collected
      using functional magnetic resonance imaging (fMRI) confirmed our predictions that
      activity in ventral premotor cortex and middle temporal gyrus near the
      extrastriate body area varies both as a function of the valence of the target and
      the extent to which actions are identified as goal-directed. In addition, the
      inferior parietal lobule is preferentially engaged when participants identify the
      actions of mentalized targets. Functional connectivity analyses suggest support
      from other regions, including the medial prefrontal cortex and amygdala, during
      mentalization. We found correlations between action identification and Autism
      Quotient scores, suggesting that understanding the neural correlates of action
      identification may enhance our understanding of the underpinnings of essential
      social cognitive processes.

PMID- 20150346
TI  - To continue or discontinue aspirin in the perioperative period: a randomized,
      controlled clinical trial.
AB  - BACKGROUND: Major adverse cardiac events (MACEs) are a common cause of death
      after non-cardiac surgery. Despite evidence for the benefit of aspirin for
      secondary prevention, it is often discontinued in the perioperative period due to
      the risk of bleeding. METHODS: We conducted a randomized, double-blind, placebo
      controlled trial in order to compare the effect of low-dose aspirin with that of
      placebo on myocardial damage, cardiovascular, and bleeding complications in high
      risk patients undergoing non-cardiac surgery. Aspirin (75 mg) or placebo was
      given 7 days before surgery and continued until the third postoperative day.
      Patients were followed up for 30 days after surgery. RESULTS: A total of 220
      patients were enrolled, 109 patients received aspirin and 111 received placebo.
      Four patients (3.7%) in the aspirin group and 10 patients (9.0%) in the placebo
      group had elevated troponin T levels in the postoperative period (P=0.10). Twelve
      patients (5.4%) had an MACE during the first 30 postoperative days. Two of these
      patients (1.8%) were in the aspirin group and 10 patients (9.0%) were in the
      placebo group (P=0.02). Treatment with aspirin resulted in a 7.2% absolute risk
      reduction [95% confidence interval (CI), 1.3-13%] for postoperative MACE. The
      relative risk reduction was 80% (95% CI, 9.2-95%). Numbers needed to treat were
      14 (95% CI, 7.6-78). No significant differences in bleeding complications were
      seen between the two groups. CONCLUSIONS: In high-risk patients undergoing non
      cardiac surgery, perioperative aspirin reduced the risk of MACE without
      increasing bleeding complications. However, the study was not powered to evaluate
      bleeding complications.

PMID- 20150347
TI  - Minimum effective bolus dose of oxytocin during elective Caesarean delivery.
AB  - BACKGROUND: The aim of this study was to determine the lowest effective bolus
      dose of oxytocin to produce adequate uterine tone (UT) during elective Caesarean
      delivery (CD). METHODS: Seventy-five pregnant patients undergoing elective CD
      under spinal anaesthesia were randomized to receive oxytocin (0.5, 1, 3, 5 units)
      or placebo. UT was assessed by a blinded obstetrician as either adequate or
      inadequate, and using a verbal numerical scale score (0-10; 0, no UT; 10, optimal
      UT) at 2, 3, 6, and 9 min after oxytocin administration. Minimum effective doses
      of oxytocin were analysed (ED(50) and ED(95)) using logistic regression. Oxytocin
      related side-effects (including hypotension) were recorded. RESULTS: There were
      no significant differences in the prevalence of adequate UT among the study
      groups at 2 min (73%, 100%, 93%, 100%, and 93% for 0, 0.5, 1, 3, and 5 units
      oxytocin, respectively). The high prevalence of adequate UT after placebo and low
      dose oxytocin precluded determination of the ED(50) and ED(95). UT scores were
      significantly lower in patients receiving 0 unit oxytocin at 2 and 3 min compared
      with 3 and 5 units oxytocin (P<0.05, respectively). The prevalence of hypotension
      was significantly higher after 5 units oxytocin vs 0 unit at 1 min (47% vs 7%;
      P=0.04). CONCLUSIONS: The routine use of 5 units oxytocin during elective CD can
      no longer be recommended, as adequate UT can occur with lower doses of oxytocin
      (0.5-3 units).

PMID- 20150348
TI  - Cuffed or uncuffed tubes during anaesthesia in infants and small children.

PMID- 20150349
TI  - Concomitant levosimendan and esmolol infusion in ischaemic cardiogenic shock.

PMID- 20150350
TI  - Cuffed and uncuffed tracheal tube in children.

PMID- 20150351
TI  - Laryngeal mask airway Supreme for asleep-awake-asleep craniotomy.

PMID- 20150354
TI  - Antigenotoxic effect of mangiferin and changes in antioxidant enzyme levels of
      Swiss albino mice treated with cadmium chloride.
AB  - Cadmium is an environmental metal toxin implicated in human diseases. Mangiferin
      (MGN), a naturally occurring glucosylxanthone, is present in Mangifera indica. In
      this study, the protective role of MGN against cadmium chloride (CdCl(2))-induced
      genotoxicity was studied in Swiss albino mice. Mice were administered with single
      intra-peritoneal (i.p.) optimal dose of MGN (2.5 mg/kg b.wt.) before treatment
      with various concentrations of CdCl(2) (7, 8, 9, 10 and 11 mg/kg b.wt.). The LD(
      50(30)) was found to be 8.5 mg/kg b.wt. for DDW + CdCl(2) group, while it was
      increased to 9.77 mg/kg after MGN treatment resulting in increase in the
      LD(50(30)) value by 1.26 mg, with a dose reduction factor (DRF) of 1.14.
      Treatment of mice to various doses of CdCl(2) resulted in a dose-dependent
      increase in the frequency of micronucleated polychromatic (MnPCE) and
      normochromatic erythrocytes (MnNCE), with corresponding decrease in the
      polychromatic / normochromatic erythrocyte ratio (PCE/NCE ratio) at various post
      treatment times. MGN (2.5 mg/kg b.wt.) pretreatment significantly (p < .001)
      reduced the frequency of MnPCE, MnNCE and increased PCE/NCE ratio when compared
      with the DDW + CdCl(2) group at all post-treatment times indicating its
      antigenotoxic effect. Further, pretreatment of MGN declined the lipid
      peroxidation (LPx) content in liver, whereas significant increase was observed in
      hepatic Glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase
      (SOD) and catalase (CAT) activity. Our study revealed that MGN has potent
      antigenotoxic effect against CdCl(2)-induced toxicity in mice, which may be due
      to the scavenging of free radicals and increased antioxidant status.

PMID- 20150355
TI  - Metabolization of nifurtimox and benznidazole in cellular fractions of rat
      mammary tissue.
AB  - Two nitroheterocyclic drugs, nifurtimox (NFX) and benznidazole (BZ), used in the
      treatment of Chagas' disease have serious side effects attributed to their
      nitroreduction to reactive metabolites. Here, we report that these drugs reach
      the mammary tissue and there they could undergo in situ bioactivation. Both were
      detected in mammary tissue from female Sprague-Dawley rats after their
      intragastric administration. Only NFX was biotransformed by pure xanthine
      oxidoreductase and from tissue cytosol. These activities were purine dependent
      and were inhibited by allopurinol. Also, only NFX was biotransformed by
      microsomes in the presence of beta-nicotinamide adenine dinucleotide phosphate,
      reduced form (NADPH), and was inhibited by carbon monoxide and partially by
      diphenyleneiodonium. NFX treatment produced significant decrease in protein
      sulfhydryl content after 1, 3 and 6 hours; no increases in protein carbonyl
      content at any time tested and significantly higher levels of lipid
      hydroperoxides at 3 and 6 hours; besides, ultrastructural observations after 24
      hours showed significant differences in epithelial cells compared to control.
      These findings indicate that NFX might be more deleterious to mammary tissue than
      BZ and could correlate with early reports on its ability to promote rat mammary
      tissue toxicity.

PMID- 20150356
TI  - Article published in cardiovascular toxicology about the cardiovascular health
      effects of carbon soot.

PMID- 20150357
TI  - Untreated poor vision: a contributing factor to late-life dementia.
AB  - Ophthalmologic abnormalities have been described in patients with dementia, but
      the extent to which poor vision and treatment for visual disorders affect
      cognitive decline is not well defined. Linked data from the Health and Retirement
      Study and Medicare files (1992-2005) were used to follow the experiences of 625
      elderly US study participants with normal cognition at baseline. The outcome was
      a diagnosis of dementia, cognitively impaired but no dementia, or normal
      cognition. Poor vision was associated with development of dementia (P = 0.0048);
      individuals with very good or excellent vision at baseline had a 63% reduced risk
      of dementia (95% confidence interval (CI): 20, 82) over a mean follow-up period
      of 8.5 years. Participants with poorer vision who did not visit an
      ophthalmologist had a 9.5-fold increased risk of Alzheimer disease (95% CI: 2.3,
      39.5) and a 5-fold increased risk of cognitively impaired but no dementia (95%
      CI: 1.6, 15.9). Poorer vision without a previous eye procedure increased the risk
      of Alzheimer disease 5-fold (95% CI: 1.5, 18.8). For Americans aged 90 years or
      older, 77.9% who maintained normal cognition had received at least one previous
      eye procedure compared with 51.7% of those with Alzheimer disease. Untreated poor
      vision is associated with cognitive decline, particularly Alzheimer disease.

PMID- 20150361
TI  - Chromosome 9p and 10q losses predict unfavorable outcome in low-grade gliomas.
AB  - The loss of chromosomes 1p-19q is the only prognostic molecular alteration
      identified in low-grade gliomas (LGGs) to date. Search for loss of heterozygosity
      (LOH) on chromosomes 1p, 9p, 10q, and 19q was performed in a series of 231 LGGs.
      Loss of chromosomes 1p-19q was strongly correlated with prolonged progression
      free survival (PFS) and overall survival (OS) in univariate and multivariate
      analyses. LOH on 9p and 10q were associated with shortened PFS (P = .01 and .03,
      respectively) on univariate analysis. On multivariate analysis, LOH on 9p
      remained significant for PFS (P = .05), whereas LOH on 10q had a significant
      effect on OS (P = .02). Search for LOH 9p and 10q appears to be a useful
      complement to analysis of chromosomes 1p-19q in LGGs.

PMID- 20150362
TI  - TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells
      in glioma patients.
AB  - The activating receptor NKG2D, expressed by natural killer (NK) cells and CD8(+)
      T cells, has a role in the specific killing of transformed cells. We examined
      NKG2D expression in patients with glioblastoma multiforme and found that NKG2D
      was downregulated on NK cells and CD8(+) T cells. Expression of NKG2D on
      lymphocytes significantly increased following tumor resection and correlated with
      an increased ability to kill NKG2D ligand-positive tumor targets. Despite the
      presence of soluble NKG2D ligands in the sera of glioblastoma patients, NKG2D
      downregulation was primarily caused by tumor-derived tumor growth factor-beta,
      suggesting that blocking of this cytokine may have therapeutic benefit.

PMID- 20150363
TI  - Bevacizumab induces regression of vestibular schwannomas in patients with
      neurofibromatosis type 2.
AB  - Bilateral vestibular schwannomas are the hallmark of neurofibromatosis type 2
      (NF2), and these tumors impair hearing and frequently lead to deafness.
      Neurosurgical intervention, the only established treatment, often damages the
      vestibular nerve. We report 2 cases in which treatment with bevacizumab (for 3
      months in one case and 6 months in the other) induced regression of progressive
      vestibular schwannomas by more than 40% and substantially improved hearing in the
      patient treated for 6 months. Bevacizumab therapy may thus provide an effective
      treatment for progressive vestibular schwannomas in patients with NF2.

PMID- 20150364
TI  - Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a
      treatment option for glioblastoma.
AB  - Glioblastoma (GB) is the most common malignant brain tumor in adults. It has
      limited treatment opportunities and is almost exclusively fatal. Owing to the
      central role the insulin-like growth factor-1 receptor (IGF-1R) plays in
      malignant cells, it has been suggested as a target for anticancer therapy
      including GB. The cyclolignan picropodophyllin (PPP) inhibits IGF-1R without
      affecting the highly homologous insulin receptor. Here, we show that PPP inhibits
      growth of human GB cell lines along with reduced phosphorylation of IGF-1R and
      AKT. In vivo, PPP-treatment causes dramatic tumor regression not only in
      subcutaneous xenografts but also in intracerebral xenografts, indicating passage
      of PPP across the blood-brain barrier.

PMID- 20150365
TI  - O6-Methylguanine DNA methyltransferase protein expression in tumor cells predicts
      outcome of temozolomide therapy in glioblastoma patients.
AB  - O(6)-Methylguanine DNA methyltransferase (MGMT) is implicated as a major
      predictive factor for treatment response to alkylating agents including
      temozolomide (TMZ) of glioblastoma multiforme (GBM) patients. However, whether
      the MGMT status in GBM patients should be detected at the level of promoter
      methylation or protein expression is still a matter of debate. Here, we compared
      promoter methylation (by methylation-specific polymerase chain reaction) and
      protein expression (by Western blot) in tumor cell explants with respect to
      prediction of TMZ response and survival of GBM patients (n = 71). Methylated MGMT
      gene promoter sequences were detected in 47 of 71 (66%) cases, whereas 37 of 71
      (52%) samples were scored positive for MGMT protein expression. Although overall
      promoter methylation correlated significantly with protein expression (chi(2)
      test, P < .001), a small subgroup of samples did not follow this association. In
      the multivariate Cox regression model, a significant interaction between MGMT
      protein expression, but not promoter methylation, and TMZ therapy was observed
      (test for interaction, P = .015). In patients treated with TMZ (n = 42), MGMT
      protein expression predicted a significantly shorter overall survival (OS; hazard
      ratio [HR] for death 5.53, 95% confidence interval [CI] 1.76-17.37; P = .003),
      whereas in patients without TMZ therapy (n = 29), no differences in OS were
      observed (HR for death 1.00, 95% CI 0.45-2.20; P = .99). These data suggest that
      lack of MGMT protein expression is superior to promoter methylation as a
      predictive marker for TMZ response in GBM patients.

PMID- 20150366
TI  - DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic
      neuroma.
AB  - Although the etiology of primary brain tumors is largely unknown, prior studies
      suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA
      repair is also likely to affect the risk of meningioma and acoustic neuroma, but
      these tumors have not been well studied. We estimated the risk of glioma (n =
      362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites
      with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA
      repair in a hospital-based, case-control study conducted by the National Cancer
      Institute. We observed significantly increased risk of meningioma with the T
      variant of GLTSCR1 rs1035938 (OR(CT/TT) = 3.5; 95% confidence interval: 1.8-6.9;
      P(trend) .0006), which persisted after controlling for multiple comparisons (P =
      .019). Significantly increased meningioma risk was also observed for the minor
      allele variants of ERCC4 rs1800067 (P(trend) .01); MUTYH rs3219466 (P(trend)
      .02), and PCNA rs25406 (P(trend) .03). The NBN rs1805794 minor allele variant was
      associated with decreased meningioma risk (P(trend) .006). Risk of acoustic
      neuroma was increased for the ERCC2 rs1799793 (P(trend) .03) and ERCC5 rs17655
      (P(trend) .05) variants and decreased for the PARP1 rs1136410 (P(trend) .03).
      Decreased glioma risk was observed with the XRCC1 rs1799782 variant (P(trend)
      .04). Our results suggest that common DNA repair variants may affect the risk of
      adult brain tumors, especially meningioma.

PMID- 20150367
TI  - A multigene predictor of outcome in glioblastoma.
AB  - Only a subset of patients with newly diagnosed glioblastoma (GBM) exhibit a
      response to standard therapy. To date, a biomarker panel with predictive power to
      distinguish treatment sensitive from treatment refractory GBM tumors does not
      exist. An analysis was performed using GBM microarray data from 4 independent
      data sets. An examination of the genes consistently associated with patient
      outcome, revealed a consensus 38-gene survival set. Worse outcome was associated
      with increased expression of genes associated with mesenchymal differentiation
      and angiogenesis. Application to formalin fixed-paraffin embedded (FFPE) samples
      using real-time reverse-transcriptase polymerase chain reaction assays resulted
      in a 9-gene subset which appeared robust in these samples. This 9-gene set was
      then validated in an additional independent sample set. Multivariate analysis
      confirmed that the 9-gene set was an independent predictor of outcome after
      adjusting for clinical factors and methylation of the methyl-guanine
      methyltransferase promoter. The 9-gene profile was also positively associated
      with markers of glioma stem-like cells, including CD133 and nestin. In sum, a
      multigene predictor of outcome in glioblastoma was identified which appears
      applicable to routinely processed FFPE samples. The profile has potential
      clinical application both for optimization of therapy in GBM and for the
      identification of novel therapies targeting tumors refractory to standard
      therapy.

PMID- 20150368
TI  - Osteopontin regulates human glioma cell invasiveness and tumor growth in mice.
AB  - Human malignant glioma cells are characterized by local invasion. In the present
      study, we investigated the role of osteopontin (OPN) in the invasiveness of human
      glioma cells isolated from grade IV tumors. We found that the expression levels
      of OPN in these cell lines paralleled matrix metalloproteinase-2 (MMP-2)
      expression and cell invasiveness potential. When U87MG glioma cells (with a high
      OPN expression level) were stably transformed with specific small hairpin RNA to
      knock down OPN expression, MMP-2 secretion, cell invasiveness, and tumor growth
      in implanted brains were dramatically reduced. Conversely, forced expression of
      OPN in GBM-SKH glioma cells (which expressed OPN at a low level) increased MMP-2
      secretion, enhanced cell invasiveness, and increased tumor growth in a rodent
      xenograft model. Expression of OPN was associated with increased expression of
      vimentin and decreased expression of glial fibrillary acidic protein. Treatment
      of glioma cells with 5-aza-2'-deoxycytidine (5-aza-dC) suppressed OPN expression
      in a concentration-dependent manner. Suppression of OPN expression by 5-aza-dC
      was associated with reductions in MMP-2 secretion, vimentin expression, cell
      invasion, intravasation, and tumor growth. These data suggest that OPN may play
      important roles in regulating cell invasion in glioma cells and that 5-aza-dC may
      serve as a therapeutic agent for human gliomas.

PMID- 20150369
TI  - Noninvasive detection of temozolomide in brain tumor xenografts by magnetic
      resonance spectroscopy.
AB  - Poor drug delivery to brain tumors caused by aberrant tumor vasculature and a
      partly intact blood-brain barrier (BBB) and blood-brain tumor barrier (BTB) can
      significantly impair the efficacy of chemotherapy. Determining drug delivery to
      brain tumors is a challenging problem, and the noninvasive detection of drug
      directly in the tumor can be critically important for accessing, predicting, and
      eventually improving effectiveness of therapy. In this study, in vivo magnetic
      resonance spectroscopy (MRS) was used to detect an anticancer agent, temozolomide
      (TMZ), in vivo in murine xenotransplants of U87MG human brain cancer. Dynamic
      magnetic resonance imaging (MRI) with the low-molecular-weight contrast agent,
      gadolinium diethylenetriaminepentaacetic acid (GdDTPA), was used to evaluate
      tumor vascular parameters. Carbon-13-labeled TMZ ([(13)C]TMZ, 99%) was
      intraperitoneally administered at a dose of approximately 140 mg/kg (450 mg/m(2),
      well within the maximal clinical dose of 1000 mg/m(2) used in humans) during the
      course of in vivo MRS experiments. Heteronuclear multiple-quantum coherence
      (HMQC) MRS of brain tumors was performed before and after i.p. administration of
      [(13)C]TMZ. Dynamic MRI experiments demonstrated slower recovery of MRI signal
      following an intravenous bolus injection of GdDTPA, higher vascular flow and
      volume obtained by T*(2)-weighted MRI, as well as enhanced uptake of the contrast
      agent in the brain tumor compared with normal brain detected by T(1)-weighted
      MRI. These data demonstrate partial breakdown of the BBB/BTB and good
      vascularization in U87MG xenografts. A [(13)C]TMZ peak was detected at 3.9 ppm by
      HMQC from a selected volume of about 0.15 cm(3) within the brain tumor with HMQC
      pulse sequences. This study clearly demonstrates the noninvasive detection of
      [(13)C]TMZ in xenografted U87MG brain tumors with MRS. Noninvasive tracking of
      antineoplastic agents using MRS can have a significant impact on brain tumor
      chemotherapy.

PMID- 20150370
TI  - Prospective evaluation of radiosurgery for hemangioblastomas in von Hippel-Lindau
      disease.
AB  - To determine the effectiveness of stereotactic radiosurgery (SRS) treatment to
      central nervous system (CNS) hemangioblastomas in von Hippel-Lindau disease
      (VHL), we analyzed long-term results in VHL patients treated with SRS. Patients
      were enrolled in a prospective VHL natural history study, undergoing SRS
      treatment of CNS hemangioblastomas. Treatment regimens, serial clinical
      evaluations, and longitudinal imaging data were analyzed. Twenty VHL patients (10
      males and 10 females) underwent SRS treatment of 44 CNS hemangioblastomas (39
      cerebellar and 5 brainstem). Mean (+/-SD) age at treatment was 37.5 +/- 12.0
      years (range: 13-67). Mean follow-up was 8.5 +/- 3.2 years (range: 3.0-17.6
      years). All patients were alive at last follow-up. Mean treated tumor volume was
      0.5 +/- 0.7 cm(3) (range: 0.01-3.6 cm(3)). Mean prescription dose was 18.9 Gy
      (range: 12-24 Gy) at the tumor margin. Local control rate at 2, 5, 10, and 15
      years after SRS treatment was 91%, 83%, 61%, and 51%, respectively. Univariate
      analysis did not identify variables associated (P > .05) with worse tumor control
      at last follow-up. Thirty-three percent of SRS-treated small (<1.0 cm diameter),
      asymptomatic tumors progressed over a long-term follow-up. There were no long
      term adverse radiation effects. Although SRS treatment of hemangioblastomas in
      VHL has a low risk for adverse radiation effects, it is associated with
      diminishing control over a long-term follow-up. These results indicate that SRS
      should not be used to prophylactically treat asymptomatic tumors and should be
      reserved for the treatment of tumors that are not surgically resectable.

PMID- 20150371
TI  - A phase I trial of erlotinib in patients with nonprogressive glioblastoma
      multiforme postradiation therapy, and recurrent malignant gliomas and
      meningiomas.
AB  - The objective of this phase I study was to determine the maximal tolerated dose
      (MTD) of erlotinib in patients with recurrent malignant gliomas (MGs) or
      recurrent meningiomas on enzyme-inducing antiepileptic drugs (EIAEDs). Dose
      escalation was by a standard 3 x 3 design. The initial starting dose of erlotinib
      was 150 mg daily. If no dose-limiting toxicity (DLT) was observed, then dose
      escalation occurs as follows: 200 mg/day, 275 mg/day, and then increased in 125
      mg increments until the MTD was reached. The MTD was defined as the dose where <
      or = 1 of 6 patients experienced a DLT and the dose above had 2 or more DLTs. The
      MTD was 650 mg/day; the observed DLTs were grade 3 rash in 2 patients at 775
      mg/day. Pharmacokinetic analysis showed a significant influence of EIAEDs on the
      metabolism of erlotinib when compared with our phase II data published
      separately. Primary toxicities were rash and diarrhea. The MTD of erlotinib in
      patients receiving EIAEDs is substantially higher than the standard dose of 150
      mg. This has important implications for further development of this drug in the
      treatment of MG as well as the optimal management of patients with other
      malignancies such as NSCLC who are on enzyme-inducing drugs.

PMID- 20150372
TI  - A phase II trial of erlotinib in patients with recurrent malignant gliomas and
      nonprogressive glioblastoma multiforme postradiation therapy.
AB  - Patients with (a) recurrent malignant glioma (MG): glioblastoma (GBM) or
      recurrent anaplastic glioma (AG), and (b) nonprogressive (NP) GBM following
      radiation therapy (RT) were eligible. Primary objective for recurrent MG was
      progression-free survival at 6 months (PFS-6) and overall survival at 12 months
      for NP GBM post-RT. Secondary objectives for recurrent MGs were response,
      survival, assessment of toxicity, and pharmacokinetics (PKs). Treatment with
      enzyme-inducing antiepileptic drugs was not allowed. Patients received 150 mg/day
      erlotinib. Patients requiring surgery were treated 7 days prior to tumor removal
      for PK analysis and effects of erlotinib on epidermal growth factor receptor
      (EGFR) and intracellular signaling pathways. Ninety-six patients were evaluable
      (53 recurrent MG and 43 NP GBM); 5 patients were not evaluable for response. PFS
      6 in recurrent GBM was 3% with a median PFS of 2 months; PFS-6 in recurrent AG
      was 27% with a median PFS of 2 months. Twelve-month survival was 57% in NP GBMs
      post-RT. Primary toxicity was dermatologic. The tissue-to-plasma ratio normalized
      to nanograms per gram dry weight for erlotinib and OSI-420 ranged from 25% to 44%
      and 30% to 59%, respectively, for pretreated surgical patients. No effect on EGFR
      or intratumoral signaling was seen. Patients with NP GBM post-RT who developed
      rash in cycle 1 had improved survival (P < .001). Single-agent activity of
      erlotinib is minimal for recurrent MGs and marginally beneficial following RT for
      NP GBM patients. Development of rash in cycle 1 correlates with survival in
      patients with NP GBM after RT.

PMID- 20150373
TI  - Inherited predisposition to glioma.
AB  - In gliomas, germline gene alterations play a significant role during malignant
      transformation of progenitor glial cells, at least for families with occurrence
      of multiple cancers or with specific hereditary cancer syndromes. Scientific
      evidence during the last few years has revealed several constitutive genetic
      abnormalities that may influence glioma formation. These germline abnormalities
      are manifested as either gene polymorphisms or hemizygous mutations of key
      regulatory genes that are involved either in DNA repair or in apoptosis. Such
      changes, among others, include hemizygous alterations of the neurofibromatosis 1
      (NF1) and p53 genes that are involved in apoptotic pathways, and alterations in
      multiple DNA repair genes such as mismatch repair (MMR) genes, x-ray cross
      complementary genes (XRCC), and O6-methylguanine-DNA methyltransferase (MGMT)
      genes. Subsequent cellular changes include somatic mutations in cell cycle
      regulatory genes and genes involved in angiogenesis and invasion, leading
      eventually to tumor formation in various stages. Future molecular diagnosis may
      identify new genomic regions that could harbor genes important for glioma
      predisposition and aid in the early diagnosis of these patients and genetic
      counseling of their families.

PMID- 20150377
TI  - Tumor stem cells, notch, and the news.

PMID- 20150378
TI  - MGMT promoter methylation is predictive of response to radiotherapy and
      prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma.
AB  - Hypermethylation of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene has
      been shown to be associated with improved outcome in glioblastoma (GBM) and may
      be a predictive marker of sensitivity to alkylating agents. However, the
      predictive utility of this marker has not been rigorously tested with regard to
      sensitivity to other therapies, namely radiation. To address this issue, we
      assessed MGMT methylation status in a cohort of patients with GBM who underwent
      radiation treatment but did not receive chemotherapy as a component of adjuvant
      treatment. Formalin-fixed, paraffin-embedded tumor samples from 225 patients with
      newly diagnosed GBM were analyzed via methylation-specific, quantitative real
      time polymerase chain reaction following bisulfite treatment on isolated DNA to
      assess MGMT promoter methylation status. In patients who received radiotherapy
      alone following resection, methylation of the MGMT promoter correlated with an
      improved response to radiotherapy. Unmethylated tumors were twice as likely to
      progress during radiation treatment. The median time interval between resection
      and tumor progression of unmethylated tumors was also nearly half that of
      methylated tumors. Promoter methylation was also found to confer improved overall
      survival in patients who did not receive adjuvant alkylating chemotherapy.
      Multivariable analysis demonstrated that methylation status was independent of
      age, Karnofsky performance score, and extent of resection as a predictor of time
      to progression and overall survival. Our data suggest that MGMT promoter
      methylation appears to be a predictive biomarker of radiation response. Since
      this biomarker has also been shown to predict response to alkylating agents,
      perhaps MGMT promoter methylation represents a general, favorable prognostic
      factor in GBM.

PMID- 20150379
TI  - Nuclear factor IA is expressed in astrocytomas and is associated with improved
      survival.
AB  - Nuclear factor IA (NFIA) is a transcription factor that specifies glial cell
      identity and promotes astrocyte differentiation during embryonic development. Its
      expression and function in gliomas are not known. Here, we examined NFIA protein
      expression in gliomas and its association with clinical outcome in pediatric
      malignant astrocytomas. We analyzed expression of NFIA by immunohistochemistry in
      88 existing glioma specimens from Childrens Hospital Los Angeles and the
      University of Southern California. Association between NFIA expression and
      progression-free survival (PFS) was examined in high-grade astrocytomas for which
      clinical data were available (n = 23, all children). NFIA was highly expressed in
      astrocytomas of all grades, but only in a minority of cells in oligodendroglial
      tumors. NFIA was expressed on a higher percentage of tumor cells in low-grade
      astrocytomas (91 +/- 5% and 77 +/- 14% in World Health Organization [WHO] I and
      II, respectively) compared with high-grade astrocytomas (48 +/- 18% and 37 +/-
      16% in WHO III and IV, respectively; P < .001, low- vs high-grade astrocytomas).
      There was a significant association between NFIA expression and PFS in children
      with astrocytoma WHO grade III or IV (Cox regression P = .019; logrank trend test
      for NFIA tertiles P = .0040 and NFIA quartiles P = .014). The association was not
      consistently significant in this small series of patients after adjustment was
      made for WHO grade III or IV. This is the first study to demonstrate expression
      of NFIA protein in astrocytomas and its association with grades of astrocytoma
      and PFS, suggesting that NFIA may play a role in astrocytoma biology.

PMID- 20150380
TI  - Hyperpolarized 13C magnetic resonance metabolic imaging: application to brain
      tumors.
AB  - In order to compare in vivo metabolism between malignant gliomas and normal
      brain, (13)C magnetic resonance (MR) spectroscopic imaging data were acquired
      from rats with human glioblastoma xenografts (U-251 MG and U-87 MG) and normal
      rats, following injection of hyperpolarized [1-(13)C]-pyruvate. The median signal
      to-noise ratio (SNR) of lactate, pyruvate, and total observed carbon-13
      resonances, as well as their relative ratios, were calculated from voxels
      containing Gadolinium-enhanced tissue in T(1) postcontrast images for rats with
      tumors and from normal brain tissue for control rats. [1-(13)C]-labeled pyruvate
      and its metabolic product, [1-(13)C]-lactate, demonstrated significantly higher
      SNR in the tumor compared with normal brain tissue. Statistical tests showed
      significant differences in all parameters (P < .0004) between the malignant
      glioma tissue and normal brain. The SNR of lactate, pyruvate, and total carbon
      was observed to be different between the U-251 MG and U-87 MG models, which is
      consistent with inherent differences in the molecular characteristics of these
      tumors. These results suggest that hyperpolarized MR metabolic imaging may be
      valuable for assessing prognosis and monitoring response to therapy for patients
      with brain tumors.

PMID- 20150381
TI  - Assessing neurotoxicity from the low-dose radiation component of radiosurgery
      using magnetic resonance spectroscopy.
AB  - The aim of the study was to determine if biochemical changes indicative of
      injury, assessed using magnetic resonance spectroscopic imaging (SI), are
      observed after stereotactic radiosurgery (SRS). The study included patients who
      underwent SI immediately before and 1, 30, and 90 days following SRS. Short TE
      spectra (TR/TE 1000/35 ms) were acquired at the SRS isocenter with a 2D PRESS-CSI
      sequence on a single 1.5 T scanner. The SRS isodose lines were overlaid on the
      magnetic resonance imaging slice utilized for SI data acquisition. N-Acetyl
      aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were computed for
      multiple voxels located between the 25 and 50 cGy isodose lines (low dose) and
      the 200 and 350 cGy isodose lines (medium dose). An analysis of variance and
      paired t-tests compared metabolite levels at different time points. Twelve
      patients were enrolled, although 3 were excluded secondary to poor spectral data
      quality or deviations from the prescribed SI protocol. The median number of
      voxels analyzed from the low- and medium-dose region was 7 and 4, respectively.
      No significant changes in metabolite peak height ratios over time were seen in
      the low-dose region, for either NAA/Cr (P = .89) or Cho/Cr (P = .85). There was
      no difference in Cho/Cr peak height ratios in the medium-dose region (P = .62).
      There was an increase in the NAA/Cr peak height ratio in the medium-dose region
      between day -1 and day +30 (P = .003), followed by a decline to baseline between
      days +30 and +90 (P = .03). We did not observe a significant decline in NAA/Cr or
      change in Cho/Cr peak heights in uninvolved brain parenchyma after SRS.

PMID- 20150382
TI  - Genome-wide profiling using single-nucleotide polymorphism arrays identifies
      novel chromosomal imbalances in pediatric glioblastomas.
AB  - Available data on genetic events in pediatric grade IV astrocytomas (glioblastoma
      [pGBM]) are scarce. This has traditionally been a major impediment in
      understanding the pathogenesis of this tumor and in developing ways for more
      effective management. Our aim is to chart DNA copy number aberrations (CNAs) and
      get insight into genetic pathways involved in pGBM. Using the Illumina Infinium
      Human-1 bead-chip-array (100K single-nucleotide polymorphisms [SNPs]), we
      genotyped 18 pediatric and 6 adult GBMs. Results were compared to BAC-array
      profiles harvested on 16 of the same pGBM, to an independent data set of 9
      pediatric high-grade astrocytomas (HGAs) analyzed on Affymetrix 250K-SNP arrays,
      and to existing data sets on HGAs. CNAs were additionally validated by real-time
      qPCR in a set of genes in pGBM. Our results identify with nonrandom clustering of
      CNAs in several novel, previously not reported, genomic regions, suggesting that
      alterations in tumor suppressors and genes involved in the regulation of RNA
      processing and the cell cycle are major events in the pathogenesis of pGBM. Most
      regions were distinct from CNAs in aGBMs and show an unexpectedly low frequency
      of genetic amplification and homozygous deletions and a high frequency of loss of
      heterozygosity for a high-grade I rapidly dividing tumor. This first, complete,
      high-resolution profiling of the tumor cell genome fills an important gap in
      studies on pGBM. It ultimately guides the mapping of oncogenic networks unique to
      pGBM, identification of the related therapeutic predictors and targets, and
      development of more effective therapies. It further shows that, despite
      commonalities in a few CNAs, pGBM and aGBMs are two different diseases.

PMID- 20150383
TI  - Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent
      glioma.
AB  - The purpose of this study is to determine prognostic factors in patients with
      high-grade recurrent glioma for 3 outcome variables (overall survival,
      progression-free survival [PFS], and PFS rate 6 months after study registration
      [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n =
      469, 1980-2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n =
      596, 1998-2002) were included. Eighteen prognostic variables were considered
      including type of treatment center (community/academic) and initial low-grade
      histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional
      hazards, and logistic regression models with bootstrap resampling were used to
      identify prognostic variables. Longer survival was associated with last known
      grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time
      from initial diagnosis (DxTime), and no baseline steroid use. Factors associated
      with longer PFS were Grade III and shorter DxTime. For patients without
      temozolomide as part of the treatment regimen, the only factor associated with
      better PFS6 was Grade III, although DxTime was important in RPA and PS was
      important in logistic regression. Grade was the most important prognostic factor
      for all three endpoints regardless of the statistical method used. Other
      important variables for one or more endpoints included age, PS, and DxTime.
      Neither type of treatment center nor initial low-grade histology was identified
      as a major predictor for any endpoint.

PMID- 20150384
TI  - Serum DNA can define tumor-specific genetic and epigenetic markers in gliomas of
      various grades.
AB  - We evaluated whether cell-free circulating DNA can be used as a noninvasive
      approach for detection of genetic/epigenetic alterations in brain tumors during
      the course of the disease. Paired tumor-serum samples from 70 patients with
      either high-grade astrocytomas (n = 41) or oligodendrogliomas of various grades
      were analyzed. The median interval between surgery and serum sampling was 1 month
      (range 0.5-168 months). DNA was extracted from whole blood, serum, and paraffin
      embedded tumor sections. Loss of heterozygosity (LOH) in chromosomes 1p, 19q, and
      10q was assessed by polymerase chain reaction (PCR)-based microsatellite
      analysis. The methylation status of O(6)-methyl guanine methyltransferase (MGMT)
      and phosphatase and tensin homolog promoters was studied by methylation-specific
      PCR. LOH and/or methylation that could identify DNA as tumor-specific was found
      in 80.5% of astrocytic tumors and in all oligodendrogliomas. The rate of serum
      detection of these biomarkers was 51% and 55%, respectively, with specificity
      around 100%. The rate of serum detection did not differ between low- and high
      grade oligodendrogliomas. Statistically significant tumor-serum concordance was
      found for MGMT methylation in both astrocytic tumors (83%; P < .001) and
      oligodendroglial tumors (72%; P < .003) and for LOH of 10q (79%; P < .002) and 1p
      (62%; P < .03) in oligodendrogliomas. We conclude that serum DNA in glial tumors
      is informative for both LOH and aberrant gene promoter methylation analysis
      during the course of the disease. The sensitivity is moderate and specificity is
      high for both low- and high-grade tumors. Future studies should identify a panel
      of biomarkers that bear the highest potential for clinical application.

PMID- 20150385
TI  - A phase I/II trial of enzastaurin in patients with recurrent high-grade gliomas.
AB  - Enzastaurin, a potent inhibitor of protein kinase C-beta, inhibits angiogenesis
      and has direct cytotoxic activity against glioma cells in preclinical studies.
      Patients with recurrent high-grade gliomas were stratified by histology and use
      of enzyme-inducing antiepileptic drugs (EIAEDs). Patients on EIAED were treated
      on the phase I dose-escalation portion of the trial with evaluation of serum
      pharmacokinetics as the primary endpoint. Patients not on EIAED were treated on
      the phase II portion of the trial with radiographic response and progression-free
      survival (PFS) as primary objectives. Patients in phase I received enzastaurin
      525-900 mg/d. Phase II patients received 500 or 525 mg/d. One hundred and
      eighteen patients were accrued to this trial. Therapy was well tolerated with
      thrombosis, thrombocytopenia, hemorrhage, and elevated alanine aminotransferase
      as the most commonly observed drug-associated grade 3 or higher toxicities.
      Patients on EIAED had serum enzastaurin exposure levels approximately 80% lower
      than those not on EIAED. Dose escalations up to 900 mg/d did not substantially
      increase serum exposure levels and a maximally tolerated dose was never reached.
      Twenty-one of 84 evaluable patients (25%) experienced an objective radiographic
      response. The 6-month PFS was 7% for patients with glioblastoma and 16% for
      patients with anaplastic glioma. Phosphorylation of glycogen synthase kinase-3 in
      peripheral blood mononuclear cells was identified as a potential biomarker of
      drug activity. Enzastaurin has anti-glioma activity in patients with recurrent
      high-grade glioma, but does not appear to have enough single-agent activity to be
      useful as monotherapy.

PMID- 20150386
TI  - The timing of cranial radiation in elderly patients with newly diagnosed
      glioblastoma multiforme.
AB  - There are few and conflicting studies on the optimal timing of initial cranial
      radiation in the treatment of glioblastoma multiforme (GBM) but none of them have
      addressed this issue in the elderly population. We used the linked Surveillance,
      Epidemiology, and End Results (SEER) Medicare database to investigate whether the
      time interval from surgery to initiation of radiation is a significant prognostic
      factor for survival in subjects aged > or =65 years with newly diagnosed GBM. Cox
      modeling was used to assess the effect of waiting time on overall survival. We
      identified a total of 1,375 patients, 296 with biopsies and 1,079 with
      resections. The median time to the initiation of radiotherapy was 15 days post
      operation (interquartile range 12-21). In the univariate Cox analysis of those
      who had debulking surgeries, a waiting time of >22 days showed a significant
      inverse relationship with survival (hazard ratio [HR] = 0.82, 95% CI 0.70-0.97, p
      = 0.02), but after adjustment for confounders, it was not a statistically
      significant factor in the final Cox model (HR = 0.99, 95% CI 0.97-1.01, p =
      0.14). Therefore, waiting time was not a significant prognostic factor for
      subjects with biopsies in both the univariate and multivariate analyses. Although
      effort should be made to initiate radiotherapy as soon as possible after surgical
      resection/biopsy, a brief delay similar to that experienced by our cohort does
      not have a significant impact on survival.

PMID- 20150388
TI  - Neurolymphomatosis: diagnosis, management, and outcomes in patients treated with
      rituximab.
AB  - Neurolymphomatosis (NL) is an uncommon syndrome of peripheral or cranial nerve
      root dysfunction secondary to infiltration by B-cell non-Hodgkin's lymphoma
      (NHL). A high index of suspicion is required as presenting symptoms are varied,
      conventional radiology has only modest sensitivity, and pathological diagnosis is
      often difficult. Treatment with chemotherapy alone has an objective response rate
      of 82%, although long-term outcomes are highly variable. This case series
      describes outcomes in four patients whose management incorporated PET scanning
      and the use of rituximab in combination with chemotherapy. PET scanning could
      often diagnose NL where other diagnostic modalities were non-diagnostic. Although
      combination therapy with rituximab and chemotherapy has been shown to be superior
      to chemotherapy alone in other forms of NHL, this does not appear to be the case
      in patients with NL. This may reflect the inability of rituximab to adequately
      penetrate into the central and peripheral nervous system. This is supported by
      the common finding that patients will relapse solely with NL despite on-going
      complete remission at sites outside the nervous system. The prognosis of these
      patients is poor, with the disease often following a progressive course despite
      treatment.

PMID- 20150387
TI  - The functional role of Notch signaling in human gliomas.
AB  - Gliomas are among the most devastating adult tumors for which there is currently
      no cure. The tumors are derived from brain glial tissue and comprise several
      diverse tumor forms and grades. Recent reports highlight the importance of cancer
      initiating cells in the malignancy of gliomas. These cells have been referred to
      as brain cancer stem cells (bCSC), as they share similarities to normal neural
      stem cells in the brain. The Notch signaling pathway is involved in cell fate
      decisions throughout normal development and in stem cell proliferation and
      maintenance. The role of Notch in cancer is now firmly established, and recent
      data implicate a role for Notch signaling also in gliomas and bCSC. In this
      review, we explore the role of the Notch signaling pathway in gliomas with
      emphasis on its role in normal brain development and its interplay with pathways
      and processes that are characteristic of malignant gliomas.

PMID- 20150390
TI  - A technique for arthroscopic all-inside suturing in the wrist.
AB  - A technique for arthroscopic all-inside suturing in the wrist is presented. The
      procedure allows placement of the knot inside the joint without additional
      incisions. We have applied it in cases of dorsal, foveal and coronal tears of the
      triangular fibrocartilage. No special instrument is required apart from a Tuohy
      needle.

PMID- 20150391
TI  - Pins and rubber traction system for intra-articular proximal interphalangeal
      joint fractures revisited.
AB  - The Pins and Rubber Traction System (PRTS) can be used to treat proximal
      interphalangeal intra-articular fractures. Our experience is that outcomes are
      not always excellent and that many patients have reduced joint function or
      residual deformities. The aim of this study was to evaluate the reasons behind
      the poorer outcomes of some of the patients treated with this system. A
      retrospective clinical and radiological evaluation was performed on 15 patients
      after a minimum of 2 years' follow-up. The mean interphalangeal joint flexion
      range was 66 degrees (range 0-100) in our series. The review of the literature
      shows an average active interphalangeal joint flexion of 78 degrees (range 64
      95). Reasons for this difference include preoperative delay, technical
      deficiencies, the learning curve, a lack in postoperative physiotherapy and
      degenerative changes due to the longer follow-up. Although the Pins and Rubber
      Traction System seems a simple procedure, a learning curve is necessary to avoid
      pitfalls.

PMID- 20150392
TI  - Ulnar ray deficiency: a review of the classification systems, the clinical
      features in 72 cases, and related developmental biology.
AB  - Ulnar ray deficiency is rare and has a variable presentation. As a result, there
      are many different classification systems for this anomaly. Furthermore, the
      developmental biology of the anomaly is still not fully understood. The aim of
      this article is to review the previous classification systems, present the
      clinical features in 72 cases and discuss the developmental biology of ulnar ray
      deficiency.

PMID- 20150393
TI  - Outcomes of nerve reconstruction for radial nerve injuries based on the level of
      injury in 244 operative cases.
AB  - We report a single surgeon series of 244 patients with radial nerve injuries who
      had nerve repair, neurolysis, or nerve graft over a 17-year period. 44 patients
      had a Level I or infraclavicular injury, 37 had a Level II injury within the
      spiral groove of the humerus, 104 had a Level III injury from the lateral arm to
      antebrachial fossa and 64 had a Level IV injury affecting the posterior
      interosseous nerve. Nerve grafting was used most frequently in all groups, and
      was the only method of reconstruction for level II injury. At 21.5 months follow
      up, Level IV injuries had significantly better outcome of finger and thumb
      extension, while wrist extension recovered in at least 80% of the patients
      irrespective of the level of injury. The radial nerve recovered better if
      repaired or reconstructed within 5 months of injury.

PMID- 20150395
TI  - Validity of patient-derived disability and clinical data in multiple sclerosis.
AB  - Patient-derived historical data are widely employed to make fundamental
      management decisions in multiple sclerosis, although the validity of the
      information provided is unclear. The objectives of this study were to determine
      validity of patient-derived historical data and to describe the utility of a
      locally relevant, patient-administered questionnaire designed to ascertain
      current disability and other important disease milestones. A well-described
      cohort of 99 patients was identified for whom comparable, detailed, prospective
      longitudinal clinician-derived data were available. Patient-derived data were
      collected by completion of a standardized questionnaire or telephone interview
      for comparison. Reliability analysis for current Expanded Disability Status Scale
      (EDSS) demonstrated an intraclass correlation coefficient of 0.79 between
      questionnaire and clinician-derived data in 79 patients, with complete agreement
      in 75.9%. Intraclass correlation coefficient for year of disease onset, diagnosis
      and onset of secondary progression was 0.86, 0.91 and 0.78, respectively. Time to
      EDSS >4.0, 6.0 and 8.0 all had an intraclass correlation coefficient of >0.9.
      Less robust agreement was observed for current disease course (Kappa coefficient
      0.71), initial relapse rate (intraclass correlation coefficient 0.37) and
      clinical features at disease onset (Kappa 0.25). We conclude that self-reported
      questionnaires can provide reliable current and retrospective data on time-to
      disability milestones with high levels of correlation observed for some
      additional elements, supporting the use of selected components of patient-derived
      data in clinical practice and for epidemiological studies.

PMID- 20150396
TI  - Visuo-proprioceptive training reduces risk of falls in patients with multiple
      sclerosis.
AB  - Lack of balance and falls are common and disabling symptoms of multiple
      sclerosis. The aim of this study was to investigate the effectiveness of a novel
      visuo-proprioceptive feedback training in ameliorating balance and reducing the
      risk of falls. Patients with multiple sclerosis with unrestricted walking ability
      and healthy age/sex-matched controls were recruited. After a baseline clinical
      evaluation, including a postural assessment in double- (stabilometric test) and
      single-leg stance (monopodalic test) by a computerized postural recorder device,
      patients were submitted to a run-in period lasting 6 weeks without any
      rehabilitative intervention. Two further clinical and postural evaluations before
      and after a 6-week period of training were performed. The training protocol
      provided static and dynamic exercises both in double- and single-leg stance, with
      and without a translating Freeman-like board. Visual feedback was shown on the
      computer screen during the exercises. We recruited 40 consecutive patients and 12
      controls. Patients had significantly poorer postural performances than controls.
      Twenty-eight patients completed the study follow-up. No significant changes in
      risk of falls emerged after the run-in period. A significant reduction in the
      median percentage of risk of falls in single-leg stance (open eyes: 39.3 versus
      15.7; closed eyes: 67.3 versus 52.6; p < 0.001, respectively) were observed after
      rehabilitation. Moreover, an improvement in walking speed (median time: 7.4 s
      versus 6.3; p = 0.001) was detected in the absence of Expanded Disability Status
      Scale changes. We conclude that visuo-proprioceptive training improves balance
      and reduces falls in multiple sclerosis.

PMID- 20150394
TI  - Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and
      human pharmacokinetic parameters.
AB  - Lipoic acid is a natural antioxidant available as an oral supplement from a
      number of different manufacturers. Lipoic acid administered subcutaneously is an
      effective therapy for murine experimental autoimmune encephalomyelitis, a model
      of multiple sclerosis. The aim of this study was to compare serum lipoic acid
      levels with oral dosing in patients with multiple sclerosis with serum levels in
      mice receiving subcutaneous doses of lipoic acid. We performed serum
      pharmacokinetic studies in patients with multiple sclerosis after a single oral
      dose of 1200 mg lipoic acid. Patients received one of the three different racemic
      formulations randomly: tablet (Formulation A) and capsules (Formulations B and
      C). Mice pharmacokinetic studies were performed with three different subcutaneous
      doses (20, 50 and 100 mg/kg racemic lipoic acid). The pharmacokinetic parameters
      included Maximum Serum Concentrations (C(max) in microg/ml) and area under the
      curve (0-infinity) (AUC ( 0-infinity) in microg*min/ml). We found mean C(max) and
      AUC (0-infinity) in patients with multiple sclerosis as follows: group A (N = 7)
      3.8 +/- 2.6 and 443.1 +/- 283.9; group B (N = 8) 9.9 +/- 4.5 and 745.2 +/- 308.7
      and group C (N = 8) 10.3 +/- 3.8 and 848.8 +/- 360.5, respectively. Mean C(max)
      and AUC (0-infinity) in the mice were: 100 mg/kg lipoic acid: 30.9 +/- 2.9 and
      998 +/- 245; 50 mg/kg lipoic acid: 7.6 +/- 1.4 and 223 +/- 20; 20 mg/kg lipoic
      acid: 2.7 +/- 0.7 and 119 +/- 33. We conclude that patients taking 1200 mg of
      lipoic acid from two of the three oral formulations achieved serum C(max) and AUC
      levels comparable to that observed in mice receiving 50 mg/kg subcutaneous dose
      of lipoic acid, which is a highly therapeutic dose in experimental autoimmune
      encephalomyelitis. A dose of 1200 mg oral lipoic acid can achieve therapeutic
      serum levels in patients with multiple sclerosis.

PMID- 20150397
TI  - Low level of systemic autoimmunity in Western Australian multiple sclerosis
      patients.
AB  - Previous autoantibody (AAb) studies in multiple sclerosis MS have produced
      conflicting results. The objective of this study was to determine AAb frequency
      and association with the HLA-DRB1 genotype. Antinuclear antibody, antithyroid
      peroxidase and anti-aquaporin-4 assays and HLA-DRB1 genotyping were performed in
      198 MS patients and 188 controls. There were no significant differences in AAb
      frequency or titres between MS and control subjects. AQP4-IgG was not found in
      any MS patients. There was no correlation between AAbs and HLA-DRB1 alleles. In
      conclusion, this study failed to confirm previous reports of increased AAbs in MS
      or to show an association between HLA-DRB1 genotype and the presence of AAbs.

PMID- 20150398
TI  - Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing
      remitting active multiple sclerosis patients: a longitudinal controlled trial of
      combination therapy.
AB  - A large body of evidence suggests that, besides their cholesterol-lowering
      effect, statins exert anti-inflammatory action. Consequently, statins may have
      therapeutic potential in immune-mediated disorders such as multiple sclerosis.
      Our objectives were to determine safety, tolerability and efficacy of low-dose
      atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients
      responding poorly to interferon beta-1a alone. Relapsing-remitting multiple
      sclerosis patients, aged 18-50 years, with contrast-enhanced lesions or relapses
      while on therapy with interferon beta-1a 44 microg (three times weekly) for 12
      months, were randomized to combination therapy (interferon + atorvastatin 20 mg
      per day; group A) or interferon alone (group B) for 24 months. Patients underwent
      blood analysis and clinical assessment with the Expanded Disability Status Scale
      every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at
      screening, and 12 and 24 months thereafter. Primary outcome measure was contrast
      enhanced lesion number. Secondary outcome measures were number of relapses, EDSS
      variation and safety laboratory data. Forty-five patients were randomized to
      group A (n = 21) or B (n = 24). At 24 months, group A had significantly fewer
      contrast-enhanced lesions versus baseline (p = 0.007) and significantly fewer
      relapses versus the two pre-randomization years (p < 0.001). At survival
      analysis, the risk for a 1-point EDSS increase was slightly higher in group B
      than in group A (p = 0.053). Low-dose atorvastatin may be beneficial, as add-on
      therapy, in poor responders to high-dose interferon beta-1a alone.

PMID- 20150400
TI  - The association between California Verbal Learning Test performance and fibre
      impairment in multiple sclerosis: evidence from diffusion tensor imaging.
AB  - The California Verbal Learning Test (CVLT) is recognized as a standard clinical
      tool for assessing episodic memory difficulties in multiple sclerosis (MS), but
      its neural correlates have not yet been examined in detail in this patient
      population. We combined neuropsychological examination and diffusion tensor
      imaging (DTI) analysis in a group of MS patients (N = 50) and demographically
      matched healthy participants (N = 20). We investigated the degree of impairment
      of the uncinate fascicle (UF), the superior longitudinal fascicle (SLF), the
      fornix (FX) and the cingulum (CG). The patients were impaired on all CVLT
      parameters and the DTI parameters correlated moderately with disease-related
      variables. Regression analyses in the complete study sample showed that CVLT
      learning scores correlated with impairment of the right UF. This association
      reached marginal significance in the patient sample. In contrast to other studies
      claiming retrieval deficits, our results suggest that encoding and consolidation
      deficits may play a major role in verbal memory impairments in MS. The findings
      also provide evidence for an association between degree of myelination of
      prefrontal fibre pathways and encoding efficiency. Finally, DTI-derived
      measurements appear to reflect disease progression in MS. The results are
      discussed in light of functional MRI studies investigating compensatory brain
      activity during cognitive processing in MS.

PMID- 20150401
TI  - Skin deposition of nickel, cobalt, and chromium in production of gas turbines and
      space propulsion components.
AB  - Skin exposure to nickel, cobalt, and chromium may cause sensitization and
      allergic contact dermatitis and it is known that many alloys and platings may
      release significant amounts of the metals upon contact with skin. Occupational
      exposure to these sensitizing metals has been studied in different settings with
      regards to airborne dust and different biological end points, but little is known
      about deposition on skin from airborne dust and direct contact with materials
      containing the metals. In this study, skin deposition was studied in 24 workers
      in an industry for development and manufacturing of gas turbines and space
      propulsion components. The workers were employed in three departments,
      representing different exposure scenarios: tools sharpening of hard metal items,
      production of space propulsion structures, and thermal application of different
      metal-containing powders. A novel acid wipe sampling technique was used to sample
      metals from specific skin surfaces on the hands and the forehead of the workers.
      Total amounts of nickel, cobalt, and chromium were measured by inductively
      coupled plasma mass spectrometry. The result showed that nickel, cobalt, and
      chromium could be detected on all skin surfaces sampled. The highest level of
      nickel was 15 microg cm(-2) h(-1), the highest for cobalt was 4.5 microg cm(-2)
      h(-1), and for chromium 0.6 microg cm(-2) h(-1). The three departments had
      different exposures regarding the metals. The highest levels of nickel on the
      skin of the workers were found in the thermal applications department, cobalt in
      the tools sharpening department, and chromium in the space propulsion components
      department. In conclusion, the workers' exposure to the metals was more likely to
      come from direct skin contact with items, rather than from airborne dust, based
      on the fact that the levels of metals were much higher on the fingers than on the
      back side of the hands and the forehead. The skin exposure levels of nickel and
      cobalt detected are judged capable to induce sensitization and elicit allergic
      contact dermatitis.

PMID- 20150402
TI  - Parasympathetic cholinergic transmission, minus the vesicles.

PMID- 20150404
TI  - Accuracy of consonant-vowel syllables in young cochlear implant recipients and
      hearing children in the single-word period.
AB  - PURPOSE: Attaining speech accuracy requires that children perceive and attach
      meanings to vocal output on the basis of production system capacities. Because
      auditory perception underlies speech accuracy, profiles for children with hearing
      loss (HL) differ from those of children with normal hearing (NH). METHOD: To
      understand the impact of auditory history on emergence of speech capacities, the
      authors compared consonant-vowel (CV) syllable accuracy in early words in 4 NH
      children and 4 children with HL who received cochlear implantation (CI) before
      age 2 years. Participants were video-recorded monthly for 6 months following word
      onset. CV vocalizations were coded perceptually with broad phonetic
      transcription. Observed-to-expected ratios of CV productions and accuracy were
      tested with chi-square analysis. An ordered multinomial model tested level of
      accuracy, including both accuracy and error patterns. RESULTS: Most frequently
      produced sequences were most accurately produced across group and time. NH
      children were more accurate overall than children with CI. Both groups improved
      accuracy over time by decreasing partially accurate productions (accurate
      consonant-inaccurate vowel). Both groups favored CV patterns with compatible
      place of articulation between consonant and vowel in absolute frequency and level
      of accuracy. CONCLUSION: Differences in emergence of CV syllable accuracy arise
      from differences in auditory perception between the NH and CI groups.

PMID- 20150405
TI  - Examining relationships among dialect variation, literacy skills, and school
      context in first grade.
AB  - PURPOSE: This study examined relationships between the use of nonmainstream
      American English dialects, literacy skills, and school environment among
      typically developing first graders (n = 617), of whom 48% were African American
      and 52% were White, in order to describe and better understand the difficulties
      many children from linguistically diverse backgrounds experience while learning
      to read. METHOD: Using hierarchical linear modeling, the authors examined the
      linear and quadratic relationships between students' dialect variation (DVAR) and
      their vocabulary, phonological awareness, and word reading skills, taking into
      account school environment, specifically schoolwide socioeconomic status (SES).
      RESULTS: The relationships between DVAR and literacy outcomes depended on the
      outcome of interest and school SES. However, children's race did not generally
      affect the trajectory or strength of the relationships between outcomes and
      dialect variation. For vocabulary and word reading, the association was
      nonlinear, that is, U-shaped, but this depended on school SES. For phonological
      awareness, a negative linear relationship was observed that did not depend on
      school SES. CONCLUSIONS: The results inform theories on the relationship between
      DVAR and literacy achievement and suggest a more complex explanation of how
      nonmainstream American English dialect use might influence how young children
      learn to read.

PMID- 20150407
TI  - Phonological acquisition in bilingual Spanish-English speaking children.
AB  - PURPOSE: In this study, the authors aimed to determine how between-language
      interaction contributes to phonological acquisition in bilingual Spanish-English
      speaking children. METHOD: A total of 24 typically developing children, ages 3;0
      (years;months) to 4;0, were included in this study: 8 bilingual Spanish-English
      speaking children, 8 monolingual Spanish speakers, and 8 monolingual English
      speakers. Single word and connected speech samples were obtained for each child.
      This study examined interaction between the two languages of bilingual children
      during phonological acquisition through the measurement of (a) transfer (the
      frequency and types of phonological transfer present in the speech of bilingual
      children); (b) deceleration (a slower rate of acquisition for bilinguals as
      compared with monolinguals); and (c) acceleration (a faster rate of acquisition
      for bilinguals as compared with monolinguals. RESULTS: Findings demonstrated that
      (a) transfer was evident in the productions of bilingual children, (b)
      differences were found in accuracy between monolingual and bilingual children,
      and (c) sound frequency did not predict differential accuracy of either
      phonetically similar sounds between languages or phonetically dissimilar sounds
      specific to Spanish or English. IMPLICATIONS: The results from this study
      indicate that transfer, deceleration, and a possible variation of the
      acceleration hypothesis occur in bilingual phonological acquisition. Evidence was
      found for separation and interaction between the bilingual children's 2 languages
      (J. Paradis & F. Genesee, 1996).

PMID- 20150406
TI  - Lexical-semantic organization in children with specific language impairment.
AB  - PURPOSE: To determine whether children with specific language impairment (SLI)
      show deficits in lexical-semantic organization and, if so, whether these deficits
      are commensurate with their delay in vocabulary size and whether the deficits
      affect all children with SLI. METHOD: Fourteen children with SLI, 14 age matches
      (AM), and 14 expressive vocabulary matches (VM) generated 3 associations to each
      of 48 words. Associations were coded as semantic (e.g., dog-pet), clang (e.g.,
      cow-how), or erroneous (e.g., spoon-Disney). RESULTS: Relative to the AM
      children, children with SLI produced fewer semantic responses, more clangs, and
      more errors. Relative to the VM children, fewer semantic responses and more
      errors in the children with SLI were found in by-item analyses. Across
      elicitation trials, semantic responses decreased in the AM and VM children but
      remained stable in the SLI children. Examination of individual performance in the
      SLI group revealed that poor semantic performance was associated with a deficit
      in expressive vocabulary and a gap between receptive and expressive vocabularies.
      CONCLUSIONS: Significant variability in lexical-semantic organization skills
      exists among children with SLI. Deficits in lexical-semantic organization were
      demonstrated by a subgroup of children with SLI who likely had concomitant word
      finding difficulties.

PMID- 20150408
TI  - Initial acquisition of mental graphemic representations in children with language
      impairment.
AB  - PURPOSE: The authors examined initial acquisition of mental graphemic
      representations (MGRs) for a set of pseudowords in children with language
      impairment (LI). They also determined whether the linguistic properties of the
      words (i.e., phonotactic and orthotactic probabilities) influenced MGR learning
      and whether the ability to acquire initial MGRs was related to performance on
      reading and spelling measures. The authors compared these children's initial
      acquisition of MGRs to a group of children with typical language (TL) skills.
      METHOD: A written fast mapping procedure was administered to 25 kindergarten
      children with LI and 31 with TL. During the procedure, the children were exposed
      to novel pseudowords varying in phonotactic and orthotactic probabilities in a
      computer-based, storybook reading task and then were asked to generate and
      identify those pseudoword spellings. Additionally, reading and spelling tasks
      were administered. RESULTS: Children with LI acquired some initial MGRs as
      evidenced by their ability to identify some pseudowords; however, their ability
      to identify and generate pseudowords was significantly poorer than that of the
      comparison group. Similar to their TL peers, the ability to identify pseudoword
      spellings by children with LI was affected by the linguistic properties of words,
      and written fast mapping performance was related to spelling performance.
      However, unlike the comparison group, written fast mapping performance of
      children with LI was not related to performance on a reading composite measure.
      CONCLUSIONS: The authors propose that children with LI are less robust at
      developing initial MGRs than are children with TL and that this poor ability to
      acquire initial MGRs likely places them at risk for later literacy deficits.

PMID- 20150409
TI  - Language and social factors in the use of cell phone technology by adolescents
      with and without specific language impairment (SLI).
AB  - PURPOSE: This study aimed to compare cell phone use (both oral and text-based) by
      adolescents with and without specific language impairment (SLI) and examine the
      extent to which language and social factors affect frequency of use. METHOD: Both
      interview and diary methods were used to compare oral and text-based
      communication using cell phones by 17-year-olds: 52 adolescents with SLI and 52
      typically developing (TD) peers. RESULTS: Overall, adolescents with SLI are
      motivated users of mobile technology, and they engage with both oral uses
      (phoning) and text-based uses (text messaging). However, adolescents with SLI do
      not exchange text messages as often as their TD peers. Social rather than
      language factors are associated with frequency of cell phone use in adolescence.
      CONCLUSIONS: These findings indicate that social difficulties restrict text-based
      uses of cell phones by adolescents with SLI, which can in turn reduce the
      opportunities that these adolescents have to develop social networks and make
      arrangements to engage in peer social interaction.

PMID- 20150410
TI  - Conversational language use as a predictor of early reading development: language
      history as a moderating variable.
AB  - PURPOSE: The present study examined the nature of concurrent and predictive
      associations between conversational language use and reading development during
      early school-age years. METHOD: Language and reading data from 380 twins in the
      Western Reserve Reading Project were examined via phenotypic correlations and
      multilevel modeling on exploratory latent factors. RESULTS: In the concurrent
      prediction of children's early reading abilities, a significant interaction
      emerged between children's conversational language abilities and their history of
      reported language difficulties. Specifically, conversational language
      concurrently predicted reading development above and beyond variance accounted
      for by formal vocabulary scores, but only in children with a history of reported
      language difficulties. A similar trend was noted in predicting reading skills 1
      year later, but the interaction was not statistically significant. CONCLUSIONS:
      Findings suggest a more nuanced view of the association between spoken language
      and early reading than is commonly proposed. One possibility is that children
      with and without a history of reported language difficulties rely on different
      skills, or the same skills to differing degrees, when completing early reading
      related tasks. Future studies should examine the causal link between
      conversational language and early reading specifically in children with a history
      of reported language difficulties.

PMID- 20150411
TI  - MULTICOM: a multi-level combination approach to protein structure prediction and
      its assessments in CASP8.
AB  - MOTIVATION: Protein structure prediction is one of the most important problems in
      structural bioinformatics. Here we describe MULTICOM, a multi-level combination
      approach to improve the various steps in protein structure prediction. In
      contrast to those methods which look for the best templates, alignments and
      models, our approach tries to combine complementary and alternative templates,
      alignments and models to achieve on average better accuracy. RESULTS: The multi
      level combination approach was implemented via five automated protein structure
      prediction servers and one human predictor which participated in the eighth
      Critical Assessment of Techniques for Protein Structure Prediction (CASP8), 2008.
      The MULTICOM servers and human predictor were consistently ranked among the top
      predictors on the CASP8 benchmark. The methods can predict moderate- to high
      resolution models for most template-based targets and low-resolution models for
      some template-free targets. The results show that the multi-level combination of
      complementary templates, alternative alignments and similar models aided by model
      quality assessment can systematically improve both template-based and template
      free protein modeling. AVAILABILITY: The MULTICOM server is freely available at
      http://casp.rnet.missouri.edu/multicom_3d.html .

PMID- 20150412
TI  - Operon structure of Staphylococcus aureus.
AB  - In bacteria, gene regulation is one of the fundamental characteristics of
      survival, colonization and pathogenesis. Operons play a key role in regulating
      expression of diverse genes involved in metabolism and virulence. However, operon
      structures in pathogenic bacteria have been determined only by in silico
      approaches that are dependent on factors such as intergenic distances and
      terminator/promoter sequences. Knowledge of operon structures is crucial to fully
      understand the pathophysiology of infections. Presently, transcriptome data
      obtained from growth curves in a defined medium were used to predict operons in
      Staphylococcus aureus. This unbiased approach and the use of five highly
      reproducible biological replicates resulted in 93.5% significantly regulated
      genes. These data, combined with Pearson's correlation coefficients of the
      transcriptional profiles, enabled us to accurately compile 93% of the genome in
      operon structures. A total of 1640 genes of different functional classes were
      identified in operons. Interestingly, we found several operons containing
      virulence genes and showed synergistic effects for two complement convertase
      inhibitors transcribed in one operon. This is the first experimental approach to
      fully identify operon structures in S. aureus. It forms the basis for further in
      vitro regulation studies that will profoundly advance the understanding of
      bacterial pathophysiology in vivo.

PMID- 20150413
TI  - Prediction of alternative isoforms from exon expression levels in RNA-Seq
      experiments.
AB  - Alternative splicing, polyadenylation of pre-messenger RNA molecules and
      differential promoter usage can produce a variety of transcript isoforms whose
      respective expression levels are regulated in time and space, thus contributing
      specific biological functions. However, the repertoire of mammalian alternative
      transcripts and their regulation are still poorly understood. Second-generation
      sequencing is now opening unprecedented routes to address the analysis of entire
      transcriptomes. Here, we developed methods that allow the prediction and
      quantification of alternative isoforms derived solely from exon expression levels
      in RNA-Seq data. These are based on an explicit statistical model and enable the
      prediction of alternative isoforms within or between conditions using any known
      gene annotation, as well as the relative quantification of known transcript
      structures. Applying these methods to a human RNA-Seq dataset, we validated a
      significant fraction of the predictions by RT-PCR. Data further showed that these
      predictions correlated well with information originating from junction reads. A
      direct comparison with exon arrays indicated improved performances of RNA-Seq
      over microarrays in the prediction of skipped exons. Altogether, the set of
      methods presented here comprehensively addresses multiple aspects of alternative
      isoform analysis. The software is available as an open-source R-package called
      Solas at http://cmb.molgen.mpg.de/2ndGenerationSequencing/Solas/.

PMID- 20150414
TI  - Characteristics of DNA-binding proteins determine the biological sensitivity to
      high-linear energy transfer radiation.
AB  - Non-homologous end-joining (NHEJ) and homologous recombination repair (HRR),
      contribute to repair ionizing radiation (IR)-induced DNA double-strand breaks
      (DSBs). Mre11 binding to DNA is the first step for activating HRR and Ku binding
      to DNA is the first step for initiating NHEJ. High-linear energy transfer (LET)
      IR (such as high energy charged particles) killing more cells at the same dose as
      compared with low-LET IR (such as X or gamma rays) is due to inefficient NHEJ.
      However, these phenomena have not been demonstrated at the animal level and the
      mechanism by which high-LET IR does not affect the efficiency of HRR remains
      unclear. In this study, we showed that although wild-type and HRR-deficient mice
      or DT40 cells are more sensitive to high-LET IR than to low-LET IR, NHEJ
      deficient mice or DT40 cells are equally sensitive to high- and low-LET IR. We
      also showed that Mre11 and Ku respond differently to shorter DNA fragments in
      vitro and to the DNA from high-LET irradiated cells in vivo. These findings
      provide strong evidence that the different DNA DSB binding properties of Mre11
      and Ku determine the different efficiencies of HRR and NHEJ to repair high-LET
      radiation induced DSBs.

PMID- 20150416
TI  - A synthetic circuit for selectively arresting daughter cells to create aging
      populations.
AB  - The ability to engineer genetic programs governing cell fate will permit new
      safeguards for engineered organisms and will further the biological understanding
      of differentiation and aging. Here, we have designed, built and implemented a
      genetic device in the budding yeast Saccharomyces cerevisiae that controls cell
      cycle progression selectively in daughter cells. The synthetic device was built
      in a modular fashion by combining timing elements that are coupled to the cell
      cycle, i.e. cell-cycle specific promoters and protein degradation domains, and an
      enzymatic domain which conditionally confers cell arrest. Thus, in the presence
      of a drug, the device is designed to arrest growth of only newly-divided daughter
      cells in the population. Indeed, while the engineered cells grow normally in the
      absence of drug, with the drug the engineered cells display reduced, linear
      growth on the population level. Fluorescence microscopy of single cells shows
      that the device induces cell arrest exclusively in daughter cells and radically
      shifts the age distribution of the resulting population towards older cells. This
      device, termed the 'daughter arrester', provides a blueprint for more advanced
      devices that mimic developmental processes by having control over cell growth and
      death.

PMID- 20150417
TI  - A TAD better for myeloma therapy?
AB  - In this issue of Blood, Lokhorst and colleagues report on the results of HOVON
      50, a phase 3 randomized trial designed to evaluate the effects of thalidomide
      during induction treatment and as maintenance in patients with multiple myeloma.
      There were 556 patients randomly assigned either to 3 cycles of VAD or to TAD.
      All patients were to receive high-dose melphalan with autologous stem cell
      support followed by maintenance with interferon for the VAD arm or thalidomide
      for the TAD arm.(1) This study together with other randomized and nonrandomized
      trials establish a definitive role for thalidomide as induction therapy in
      conjunction with dexamethasone, anthracyclines, and alkylating agents.

PMID- 20150415
TI  - RNPomics: defining the ncRNA transcriptome by cDNA library generation from
      ribonucleo-protein particles.
AB  - Up to 450,000 non-coding RNAs (ncRNAs) have been predicted to be transcribed from
      the human genome. However, it still has to be elucidated which of these
      transcripts represent functional ncRNAs. Since all functional ncRNAs in Eukarya
      form ribonucleo-protein particles (RNPs), we generated specialized cDNA libraries
      from size-fractionated RNPs and validated the presence of selected ncRNAs within
      RNPs by glycerol gradient centrifugation. As a proof of concept, we applied the
      RNP method to human Hela cells or total mouse brain, and subjected cDNA
      libraries, generated from the two model systems, to deep-sequencing.
      Bioinformatical analysis of cDNA sequences revealed several hundred ncRNP
      candidates. Thereby, ncRNAs candidates were mainly located in intergenic as well
      as intronic regions of the genome, with a significant overrepresentation of
      intron-derived ncRNA sequences. Additionally, a number of ncRNAs mapped to
      repetitive sequences. Thus, our RNP approach provides an efficient way to
      identify new functional small ncRNA candidates, involved in RNP formation.

PMID- 20150418
TI  - NK-cell education: KIR-S come into play.
AB  - In this issue of Blood, Fauriat and colleagues find that the expression of
      KIR2DS1 by human NK cells is associated with a decreased responsiveness to
      various stimuli in HLA C2/C2 but not in C1/C1 persons.

PMID- 20150419
TI  - A means to an end: ubiquitination of Mpl.
AB  - In this issue of Blood, Saur and colleagues report that ubiquitin-mediated
      degradation of the Mpl receptor constrains Tpo-mediated cell proliferation,
      highlighting the importance of the E3 ubiquitin ligase c-Cbl in rapid down
      regulation of Tpo/Mpl signaling.

PMID- 20150420
TI  - Breaking barriers.
AB  - It is difficult to imagine a greater challenge to the transplantation of
      haploidentical cells than thalassemia.

PMID- 20150421
TI  - Identification of novel oxidized protein substrates and physiological partners of
      the mitochondrial ATP-dependent Lon-like protease Pim1.
AB  - ATP-dependent proteases are currently emerging as key regulators of mitochondrial
      functions. Among these proteolytic systems, Pim1, a Lon-like serine protease in
      Saccharomyces cerevisiae, is involved in the control of selective protein
      turnover in the mitochondrial matrix. In the absence of Pim1, yeast cells have
      been shown to accumulate electron-dense inclusion bodies in the matrix space, to
      lose integrity of mitochondrial genome, and to be respiration-deficient. Because
      of the severity of phenotypes associated with the depletion of Pim1, this
      protease appears to be an essential component of the protein quality control
      machinery in mitochondria and to exert crucial functions during the biogenesis of
      this organelle. Nevertheless, its physiological substrates and partners are not
      fully characterized. Therefore, we used the combination of different proteomic
      techniques to assess the nature of oxidized protein substrates and physiological
      partners of Pim1 protease under non-repressing growth conditions. The results
      presented here supply evidence that Pim1-mediated proteolysis is required for
      elimination of oxidatively damaged proteins in mitochondria.

PMID- 20150422
TI  - Processing of meiotic DNA double strand breaks requires cyclin-dependent kinase
      and multiple nucleases.
AB  - Meiotic recombination requires the formation of programmed Spo11-dependent DNA
      double strand breaks (DSBs). In Saccharomyces cerevisiae, the Sae2 protein and
      the Mre11-Rad50-Xrs2 complex are necessary to remove the covalently attached
      Spo11 protein from the DNA ends, which are then resected by so far unknown
      nucleases. Here, we demonstrate that phosphorylation of Sae2 Ser-267 by cyclin
      dependent kinase 1 (Cdk1) is required to initiate meiotic DSB resection by
      allowing Spo11 removal from DSB ends. This finding suggests that Cdk1 activity is
      required for the processing of Spo11-induced DSBs, thus providing a mechanism for
      coordinating DSB resection with progression through meiotic prophase.
      Furthermore, the helicase Sgs1 and the nucleases Exo1 and Dna2 participate in
      lengthening the 5'-3' resection tracts during meiosis by controlling a step
      subsequent to Spo11 removal.

PMID- 20150423
TI  - Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion
      kinase (FAK).
AB  - The coordinated and dynamic regulation of adhesions is required for cell
      migration. We demonstrated previously that limited proteolysis of talin1 by the
      calcium-dependent protease calpain 2 plays a critical role in adhesion
      disassembly in fibroblasts (Franco, S. J., Rodgers, M. A., Perrin, B. J., Han,
      J., Bennin, D. A., Critchley, D. R., and Huttenlocher, A. (2004) Nat. Cell Biol.
      6, 977-983). However, little is known about the contribution of other calpain
      substrates to the regulation of adhesion dynamics. We now provide evidence that
      calpain 2-mediated proteolysis of focal adhesion kinase (FAK) regulates adhesion
      dynamics in motile cells. We mapped the preferred calpain cleavage site between
      the two C-terminal proline-rich regions after Ser-745, resulting in a C-terminal
      fragment similar in size to the FAK-related non-kinase (FRNK). We generated
      mutant FAK with a point mutation (V744G) that renders FAK resistant to calpain
      proteolysis but retains other biochemical properties of FAK. Using time-lapse
      microscopy, we show that the dynamics of green fluorescent protein-talin1 are
      impaired in FAK-deficient cells. Expression of wild-type but not calpain
      resistant FAK rescues talin dynamics in FAK-deficient cells. Taken together, our
      findings suggest a novel role for calpain proteolysis of FAK in regulating
      adhesion dynamics in motile cells.

PMID- 20150424
TI  - Sekiguchi lesion gene encodes a cytochrome P450 monooxygenase that catalyzes
      conversion of tryptamine to serotonin in rice.
AB  - Serotonin is a well known neurotransmitter in mammals and plays an important role
      in various mental functions in humans. In plants, the serotonin biosynthesis
      pathway and its function are not well understood. The rice sekiguchi lesion (sl)
      mutants accumulate tryptamine, a candidate substrate for serotonin biosynthesis.
      We isolated the SL gene by map-based cloning and found that it encodes CYP71P1 in
      a cytochrome P450 monooxygenase family. A recombinant SL protein exhibited
      tryptamine 5-hydroxylase enzyme activity and catalyzed the conversion of
      tryptamine to serotonin. This pathway is novel and has not been reported in
      mammals. Expression of SL was induced by the N-acetylchitooligosaccharide
      (chitin) elicitor and by infection with Magnaporthe grisea, a causal agent for
      rice blast disease. Exogenously applied serotonin induced defense gene expression
      and cell death in rice suspension cultures and increased resistance to rice blast
      infection in plants. We also found that serotonin-induced defense gene expression
      is mediated by the RacGTPase pathway and by the G alpha subunit of the
      heterotrimeric G protein. These results suggest that serotonin plays an important
      role in rice innate immunity.

PMID- 20150425
TI  - Gas7 functions with N-WASP to regulate the neurite outgrowth of hippocampal
      neurons.
AB  - Neuritogenesis, or neurite outgrowth, is a critical process for neuronal
      differentiation and maturation in which growth cones are formed from highly
      dynamic actin structures. Gas7 (growth arrest-specific gene 7), a new member of
      the PCH (Pombe Cdc15 homology) protein family, is predominantly expressed in
      neurons and is required for the maturation of primary cultured Purkinje neurons
      as well as the neuron-like differentiation of PC12 cells upon nerve growth factor
      stimulation. We report that Gas7 co-localizes and physically interacts with N
      WASP, a key regulator of Arp2/3 complex-mediated actin polymerization, in the
      cortical region of Gas7-transfected Neuro-2a cells and growth cones of
      hippocampal neurons. The interaction between Gas7 and N-WASP is mediated by WW
      Pro domains, which is unique in the PCH protein family, where most interactions
      are of the SH3-Pro kind. The interaction contributes to the formation of membrane
      protrusions and processes by recruiting the Arp2/3 complex in a Cdc42-independent
      manner. Importantly, specific interaction between Gas7 and N-WASP is required for
      regular neurite outgrowth of hippocampal neurons. The data demonstrate an
      essential role of Gas7 through its interaction with N-WASP during neuronal
      maturation/differentiation.

PMID- 20150426
TI  - Free oligosaccharides to monitor glycoprotein endoplasmic reticulum-associated
      degradation in Saccharomyces cerevisiae.
AB  - In eukaryotic cells, N-glycosylation has been recognized as one of the most
      common and functionally important co- or post-translational modifications of
      proteins. "Free" forms of N-glycans accumulate in the cytosol of mammalian cells,
      but the precise mechanism for their formation and degradation remains unknown.
      Here, we report a method for the isolation of yeast free oligosaccharides (fOSs)
      using endo-beta-1,6-glucanase digestion. fOSs were undetectable in cells lacking
      PNG1, coding the cytoplasmic peptide:N-glycanase gene, suggesting that almost all
      fOSs were formed from misfolded glycoproteins by Png1p. Structural studies
      revealed that the most abundant fOS was M8B, which is not recognized well by the
      endoplasmic reticulum-associated degradation (ERAD)-related lectin, Yos9p. In
      addition, we provide evidence that some of the ERAD substrates reached the Golgi
      apparatus prior to retrotranslocation to the cytosol. N-Glycan structures on
      misfolded glycoproteins in cells lacking the cytosol/vacuole alpha-mannosidase,
      Ams1p, was still quite diverse, indicating that processing of N-glycans on
      misfolded glycoproteins was more complex than currently envisaged. Under ER
      stress, an increase in fOSs was observed, whereas levels of M7C, a key glycan
      structure recognized by Yos9p, were unchanged. Our method can thus provide
      valuable information on the molecular mechanism of glycoprotein ERAD in
      Saccharomyces cerevisiae.

PMID- 20150428
TI  - A protein involved in the assembly of an extracellular calcium storage matrix.
AB  - Gastroliths, the calcium storage organs of crustaceans, consist of chitin-protein
      mineral complexes in which the mineral component is stabilized amorphous calcium
      carbonate. To date, only three proteins, GAP 65, gastrolith matrix protein
      (GAMP), and orchestin, have been identified in gastroliths. Here, we report a
      novel protein, GAP 10, isolated from the gastrolith of the crayfish Cherax
      quadricarinatus and specifically expressed in its gastrolith disc. The encoding
      gene was cloned by partial sequencing of the protein extracted from the
      gastrolith matrix. Based on an assembled microarray cDNA chip, GAP 10 transcripts
      were found to be highly (12-fold) up-regulated in premolt gastrolith disc and
      significantly down-regulated in the hypodermis at the same molt stage. The
      deduced protein sequence of GAP 10 lacks chitin-binding domains and does not show
      homology to known proteins in the GenBank data base. It does, however, have an
      amino acid composition that has similarity to proteins extracted from
      invertebrate and ascidian-calcified extracellular matrices. The GAP 10 sequence
      contains a predicted signal peptide and predicted phosphorylation sites. In
      addition, the protein is phosphorylated and exhibits calcium-binding ability.
      Repeated daily injections of GAP 10 double strand RNA to premolt C.
      quadricarinatus resulted in a prolonged premolt stage and in the development of
      gastroliths with irregularly rough surfaces. These findings suggest that GAP 10
      may be involved in the assembly of the gastrolith chitin-protein-mineral complex,
      particularly in the deposition of amorphous calcium carbonate.

PMID- 20150427
TI  - Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block
      fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid
      induced toxicity.
AB  - Parkinson disease (PD) is the second most common neurodegenerative disorder after
      Alzheimer disease (AD). There is considerable consensus that the increased
      production and/or aggregation of alpha-synuclein (alpha-syn) plays a central role
      in the pathogenesis of PD and related synucleinopathies. Current therapeutic
      strategies for treating PD offer mainly transient symptomatic relief and aim at
      the restitution of dopamine levels to counterbalance the loss of dopaminergic
      neurons. Therefore, the identification and development of drug-like molecules
      that block alpha-synuclein aggregation and prevent the loss of dopaminergic
      neurons are desperately needed to treat or slow the progression of PD. Here, we
      show that entacapone and tolcapone are potent inhibitors of alpha-syn and beta
      amyloid (Abeta) oligomerization and fibrillogenesis, and they also protect
      against extracellular toxicity induced by the aggregation of both proteins.
      Comparison of the anti-aggregation properties of entacapone and tolcapone with
      the effect of five other catechol-containing compounds, dopamine, pyrogallol,
      gallic acid, caffeic acid, and quercetin on the oligomerization and
      fibrillization of alpha-syn and Abeta, demonstrate that the catechol moiety is
      essential for the anti-amyloidogenic activity. Our findings present the first
      characterization of the anti-amyloidogenic properties of tolcapone and entacapone
      against both alpha-synuclein and Abeta42 and highlight the potential of this
      class of nitro-catechol compounds as anti-amyloidogenic agents. Their inhibitory
      properties, mode of action, and structural properties suggest that they
      constitute promising lead compounds for further optimization.

PMID- 20150429
TI  - Influence of conceptual knowledge on visual object discrimination: insights from
      semantic dementia and MTL amnesia.
AB  - Recent evidence suggests that the perirhinal cortex is involved in perception of
      complex objects with ambiguous features. Anterior regions of the temporal lobes,
      including the perirhinal cortex as well as lateral cortex, are also thought to
      play a critical role in semantic memory. To understand how semantic factors might
      contribute to perceptual discrimination of complex objects, we studied visual
      object discrimination in patients with semantic dementia (SD)-a neurodegenerative
      condition characterized by progressive deterioration of semantic knowledge and
      atrophy to anterior temporal lobes (including perirhinal cortex). In 3
      experiments, we assessed discrimination of meaningful (e.g., familiar real-world
      objects) and novel (e.g., blobs) objects with varying feature ambiguity levels.
      In a fourth experiment, we compared SD patients with amnesic patients with
      nonprogressive medial temporal lobe (MTL) lesions and less impaired semantic
      memory. Across studies, patients with perirhinal damage were impaired at
      discriminating objects with a high, but not low, degree of feature ambiguity,
      consistent with previous work indicating a perceptual role for this structure.
      Stimulus meaningfulness, however, differentially influenced performance in SD
      patients compared with MTL amnesics, suggesting that perceptual representations
      of complex objects (dependent upon perirhinal cortex) interact with higher-order
      abstract conceptual representations, even for tasks with no overt semantic
      component.

PMID- 20150431
TI  - Regulation of p63 isoforms by snail and slug transcription factors in human
      squamous cell carcinoma.
AB  - TP63 is a p53-related gene that contains two alternative promoters, which give
      rise to transcripts that encode proteins with (TAp63) or without (DeltaNp63) an
      amino-transactivating domain. Whereas the expression of p63 is required for
      proper development of epithelial structures, the role of p63 in tumorigenesis
      remains unclear. Here, we investigated the role of Snail and Slug transcription
      factors, known to promote epithelial-to-mesenchymal transitions during
      development and cancer, in the regulation of p63 isoforms in human squamous cell
      carcinoma (SCC). In the present study, we observed that the expressions of DeltaN
      and TAp63 isoforms were, respectively, down- and up-regulated by both Snail and
      Slug. However, the induction of TAp63 was not directly caused by these two
      transcription factors but resulted from the loss of DeltaNp63, which acts as
      dominant-negative inhibitor of TAp63. In SCC cell lines and cancer tissues, high
      expression of Snail and Slug was also significantly associated with altered p63
      expression. Finally, we showed that DeltaNp63 silencing reduced cell-cell
      adhesion and increased the migratory properties of cancer cells. These data
      suggest that the disruption of p63 expression induced by Snail and Slug plays a
      crucial role in tumor progression. Therefore, p63 and its regulating factors
      could constitute novel prognosis markers in patients with SCC and attractive
      targets for the therapeutic modulation of neoplastic cell invasiveness.

PMID- 20150430
TI  - Autophagy is a component of epithelial cell fate in obstructive uropathy.
AB  - Epithelial cell fate and nephron loss in obstructive uropathy are not fully
      understood. We produced transgenic mice in which epithelial cells in the nephrons
      and collecting ducts were labeled with enhanced yellow fluorescent protein, and
      tracked the fate of these cells following unilateral ureteral obstruction (UUO).
      UUO led to a decrease in the number of enhanced yellow fluorescent protein
      expressing cells and down-regulation of epithelial markers, E-cadherin, and
      hepatocyte nuclear factor-1beta. Following UUO, enhanced yellow fluorescent
      protein-positive cells were confined within the tubular basement membrane, were
      not found in the renal interstitium, and did not express alpha-smooth muscle
      actin or S100A4, markers of myofibroblasts and fibroblasts. Moreover, when
      proximal tubules were labeled with dextran before UUO, dextran-retaining cells
      did not migrate into the interstitium or express alpha-smooth muscle actin. These
      results indicate that UUO leads to tubular epithelial loss but does not cause
      epithelial-to-mesenchymal transition that has been shown by others to be
      responsible for nephron loss and interstitial fibrosis. For the first time, we
      found evidence of enhanced autophagy in obstructed tubules, including
      accumulation of autophagosomes, increased expression of Beclin 1, and increased
      conversion of microtubular-associated protein 1 light chain 3-I to -II. Increased
      autophagy may represent a mechanism of tubular survival or may contribute to
      excessive cell death and tubular atrophy after obstructive injury.

PMID- 20150432
TI  - Therapeutic targeting of classical and lectin pathways of complement protects
      from ischemia-reperfusion-induced renal damage.
AB  - Ischemia-reperfusion injury is the major cause of delayed graft function in
      transplanted kidneys, an early event significantly affecting long-term graft
      function and survival. Several studies in rodents suggest that the alternative
      pathway of the complement system plays a pivotal role in renal ischemia
      reperfusion injury. However, limited information is currently available from
      humans and larger animals. Here we demonstrated that 30 minutes of ischemia
      resulted in the induction of C4d/C1q, C4d/MLB, and MBL/MASP-2 deposits in a swine
      model of ischemia-reperfusion injury. The infusion of C1-inhibitor led to a
      significant reduction in peritubular capillary and glomerular C4d and C5b-9
      deposition. Moreover, complement-inhibiting treatment significantly reduced the
      numbers of infiltrating CD163(+), SWC3a(+), CD4a(+), and CD8a(+) cells. C1
      inhibitor administration led to significant inhibition of tubular damage and
      tubular epithelial cells apoptosis. Interestingly, we report that focal C4d
      deposition colocalizes with C1q and MBL at the peritubular and glomerular
      capillary levels also in patients with delayed graft function. In conclusion, we
      demonstrated the activation and a pathogenic role of classical and lectin
      pathways of complement in a swine model of ischemia-reperfusion-induced renal
      damage. Therefore, inhibition of these two pathways might represent a novel
      therapeutic approach in the prevention of delayed graft function in kidney
      transplant recipients.

PMID- 20150433
TI  - Brain endothelial cells synthesize neurotoxic thrombin in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by neuronal death; thus, identifying
      neurotoxic proteins and their source is central to understanding and treating AD.
      The multifunctional protease thrombin is neurotoxic and found in AD senile
      plaques. The objective of this study was to determine whether brain endothelial
      cells can synthesize thrombin and thus be a source of this neurotoxin in AD
      brains. Microvessels were isolated from AD patient brains and from age-matched
      controls. Reverse transcription-PCR demonstrated that thrombin message was highly
      expressed in microvessels from AD brains but was not detectable in control
      vessels. Similarly, Western blot analysis of microvessels showed that the
      thrombin protein was highly expressed in AD- but not control-derived
      microvessels. In addition, high levels of thrombin were detected in cerebrospinal
      fluid obtained from AD but not control patients, and sections from AD brains
      showed reactivity to thrombin antibody in blood vessel walls but not in vessels
      from controls. Finally, we examined the ability of brain endothelial cells in
      culture to synthesize thrombin and showed that oxidative stress or cell signaling
      perturbations led to increased expression of thrombin mRNA in these cells. The
      results demonstrate, for the first time, that brain endothelial cells can
      synthesize thrombin, and suggest that novel therapeutics targeting vascular
      stabilization that prevent or decrease release of thrombin could prove useful in
      treating this neurodegenerative disease.

PMID- 20150434
TI  - Autophagy: cerebral home cooking.
AB  - Cell survival depends on a complex interplay of processes including homeostatic
      pathways and cytoprotective mechanisms. Autophagy is a physiological process
      involved in the basal turnover of long-lived proteins and organelles and also
      comprises an integral part of the cellular stress response. The significance of
      autophagy in regulating neural cell fate has become increasingly recognized and
      agents targeting autophagy are of increasing therapeutic interest. This review
      summarizes the recent expansion of our understanding of the scope of this
      physiological process.

PMID- 20150435
TI  - Bone marrow-derived cells contribute to fibrosis in the chronically failing
      heart.
AB  - Cardiac fibrosis contributes significantly to the phenotype of the chronically
      failing heart. It is not clear whether in this setting the fibrosis is
      contributed by native cardiac fibroblasts or alternatively by recruitment of
      cells arising from the bone marrow. We aimed to determine the contribution of
      bone marrow-derived cells to cardiac fibrosis in the failing heart and to
      investigate potentially contributing cytokines. Bone marrow-derived fibrocyte
      recruitment to the failing heart was studied in a transgenic (Mst1 mice) model of
      dilated cardiomyopathy. In conjunction, we examined the role of stromal-derived
      factor-1 (SDF-1), a key chemoattractant, by assessing myocardial expression and
      secretion by cardiomyocytes and in clinical samples. Bone marrow-derived cells
      were recruited in significantly greater numbers in Mst1 versus control mice (P <
      0.001), contributing 17 +/- 4% of the total fibroblast load in heart failure.
      Patients with heart failure had higher plasma levels of SDF-1 than healthy
      control subjects (P < 0.01). We found that cardiomyocytes constitutively secrete
      SDF-1, which is significantly up-regulated by angiotensin II. SDF-1 was shown to
      increases cardiac fibroblast migration by 59% (P < 0.05). Taken together, our
      data suggest that recruitment of bone marrow-derived cells under the influence of
      factors, including SDF-1, may play an important role in the pathogenesis of
      cardiac fibrosis in heart failure.

PMID- 20150436
TI  - Intragraft expression of the IL-10 gene is up-regulated in renal protocol
      biopsies with early interstitial fibrosis, tubular atrophy, and subclinical
      rejection.
AB  - Grafts with subclinical rejection associated with interstitial fibrosis and
      tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical
      rejection without IF/TA (SCR). Aiming to detect differences among SCR+IF/TA and
      SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and
      used a low-density array to determine levels of T(H)1 (interleukin IL-2, IL-3,
      gamma-interferon, tumor necrosis factor-alpha, lymphotoxin-alpha, lymphotoxin
      beta, granulocyte-macrophage colony-stimulating factor) and T(H)2 (IL-4, IL-5, IL
      6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell
      activation) in 31 protocol biopsies of renal allografts. Here we show that grafts
      with early IF/TA and SCR can be distinguished from grafts with SCR on the basis
      of the activation of IL-10 gene expression and of an increased infiltration by B
      lymphocytes in a cellular context in which the degree of T-cell activation is
      similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R
      mRNA. These results suggest that the up-regulation of the IL-10 gene expression,
      as well as an increased proportion of B-lymphocytes in the inflammatory
      infiltrates, might be useful as markers of early chronic lesions in grafts with
      SCR.

PMID- 20150437
TI  - Serum cellular apoptosis susceptibility protein is a potential prognostic marker
      for metastatic colorectal cancer.
AB  - Colorectal cancer has high rates of recurrence and metastasis. Many patients with
      similar histopathological features show significantly different clinical
      outcomes, and these differences are primarily related to metastases undetected by
      current diagnostic methods. There is no useful serological marker for metastatic
      disease. We investigated the cellular apoptosis susceptibility (CSE1L/CAS)
      protein in comparison with carcinoembryonic antigen (CEA) as a marker for
      metastatic colorectal cancer. Using serum from 103 patients with stage I, II,
      III, and IV disease, CSE1L was detected in 36.0% (9 of 25), 57.7% (15 of 26),
      71.4% (30 of 42), and 88.9% (8 of 9) of patients, respectively; a pathological
      CEA level was found in 16.0% (4 of 25), 42.3% (11 of 26), 47.6% (20 of 42), and
      77.8% (7 of 9) of patients, respectively; a combined CSE1L/CEA assay was detected
      in 48.0% (12 of 25), 65.4% (17 of 26), 88.1% (37 of 42), and 100% (9 of 9) of
      patients, respectively. Lymphatic metastasis is an important predictor of poor
      prognosis and crucial for determination of therapeutic strategy. Serum CSE1L was
      detected in 74.5% (38 of 51) of patients with lymph node metastasis, whereas a
      pathological CEA level was found in only 52.9% (27 of 51) of the same patients (P
      < 0.001); the combined CSE1L/CEA assay increased sensitivity to 90.2% (46 of 51).
      Animal experiments showed CSE1L reduction in B16-F10 melanoma cells correlated
      with decreased metastasis to the colorectal tract in C57BL/6 mice. These results
      indicate that assay of serum CSE1L may facilitate diagnosis of colorectal cancer
      lymphatic metastases; furthermore, CSE1L is a possible therapeutic target.

PMID- 20150438
TI  - Multiplexed assessment of the Southwest Oncology Group-directed Intergroup Breast
      Cancer Trial S9313 by AQUA shows that both high and low levels of HER2 are
      associated with poor outcome.
AB  - Assessment of key breast cancer tissue biomarkers is often done using
      nonquantitative methods. We hypothesized that use of continuous analysis of
      expression with the AQUA method of automated quantitative analysis will provide
      prognostic information beyond that attainable with conventional methods. A tissue
      microarray was made from 2123 of 3122 patients accrued to SWOG 9313, in which
      sequential doxorubicin (A) and cyclophosphamide (C) was compared with combination
      AC and in which all patients except premenopausal estrogen receptor (ER)-negative
      patients received tamoxifen. Multiplexed assays of 1) HER2 and estrogen receptor
      and 2) progesterone receptor (PgR) and p53 were performed on the two slides using
      the immunofluorescence-based AQUA method of automated quantitative analysis. Both
      ER and PgR showed unimodal distributions and significantly predicted disease-free
      survival when tested as continuous variables and adjusted for node status, tumor
      size, treatment, and menopausal status (P = 0.005 and P < 0.001, respectively).
      HER2, measured as a continuous variable, showed a biphasic effect on disease-free
      survival. Both high and low expressers of HER2 have worse outcomes (when low
      levels are equivalent to that seen in normal breast ducts). In patients who were
      uniformly treated with AC chemotherapy and tamoxifen (when indicated), both ER
      and PgR, assessed as continuous variables, were highly prognostic, whereas p53
      expression was not. This assay method may provide a new companion diagnostic
      approach for targeted therapies.

PMID- 20150439
TI  - Role of insulin-like growth factor binding protein 2 in lung adenocarcinoma: IGF
      independent antiapoptotic effect via caspase-3.
AB  - Insulin-like growth factor (IGF) signaling plays a pivotal role in cell
      proliferation and mitogenesis. Secreted IGF-binding proteins (IGFBPs) are
      important modulators of IGF bioavailability; however, their intracellular
      functions remain elusive. We sought to assess the antiapoptotic properties of
      intracellular IGFBP-2 in lung adenocarcinomas. IGFBP-2 overexpression resulted in
      a decrease in procaspase-3 expression; however, it did not influence the
      phosphorylation status of either IGF receptor or its downstream targets,
      including Akt and extracellular signal-regulated kinase. Apoptosis induced by
      camptothecin was significantly inhibited by IGFBP-2 overexpression in NCI-H522
      cells. Conversely, selective knockdown of IGFBP-2 using small-interfering RNA
      resulted in an increase in procaspase-3 expression and sensitization to
      camptothecin-induced apoptosis in NCI-H522 cells. LY294002, an inhibitor of
      phosphatidyl-inositol 3-kinase, caused a decrease in IGFBP-2 levels and enhanced
      apoptosis in combination with camptothecin. Immunohistochemistry demonstrated
      that intracellular IGFBP-2 was highly expressed in lung adenocarcinomas compared
      with normal epithelium. Intracellular IGFBP-2 and procaspase-3 were expressed in
      a mutually exclusive manner. These findings suggest that intracellular IGFBP-2
      regulates caspase-3 expression and contributes to the inhibitory effect on
      apoptosis independent of IGF. IGFBP-2, therefore, may offer a novel therapeutic
      target and serve as an antiapoptotic biomarker for lung adenocarcinoma.

PMID- 20150441
TI  - Review: electronic health records and the reliability and validity of quality
      measures: a review of the literature.
AB  - Previous reviews of research on electronic health record (EHR) data quality have
      not focused on the needs of quality measurement. The authors reviewed empirical
      studies of EHR data quality, published from January 2004, with an emphasis on
      data attributes relevant to quality measurement. Many of the 35 studies reviewed
      examined multiple aspects of data quality. Sixty-six percent evaluated data
      accuracy, 57% data completeness, and 23% data comparability. The diversity in
      data element, study setting, population, health condition, and EHR system studied
      within this body of literature made drawing specific conclusions regarding EHR
      data quality challenging. Future research should focus on the quality of data
      from specific EHR components and important data attributes for quality
      measurement such as granularity, timeliness, and comparability. Finally, factors
      associated with poor or variability in data quality need to be better understood
      and effective interventions developed.

PMID- 20150440
TI  - DNA damage and DNA damage responses in THP-1 monocytes after exposure to spores
      of either Stachybotrys chartarum or Aspergillus versicolor or to T-2 toxin.
AB  - We have characterized cell death in THP-1 cells after exposure to heat-treated
      spores from satratoxin G-producing Stachybotrys chartarum isolate IBT 9631,
      atranone-producing S. chartarum isolate IBT 9634, and sterigmatocystin-producing
      Aspergillus versicolor isolate IBT 3781, as well as the trichothecenes T-2 and
      satratoxin G. Spores induced cell death within 3-6 h, with Stachybotrys appearing
      most potent. IBT 9631 induced both apoptosis and necrosis, while IBT 9634 and IBT
      3781 induced mostly necrosis. T-2 toxin and satratoxin G caused mainly apoptosis.
      Comet assay +/- formamidopyrimidine DNA glycosylase showed that only the spore
      exposures induced early (3h) oxidative DNA damage. Likewise, only the spores
      increased the formation of reactive oxygen species (ROS), suggesting that spores
      as particles may induce ROS formation and oxidative DNA damage. Increased Ataxia
      Telangiectasia Mutated (ATM) phosphorylation, indicating DNA damage, was observed
      after all exposures. The DNA damage response induced by IBT 9631 as well as
      satratoxin G was characterized by rapid (15 min) activation of p38 and H2AX. The
      p38 inhibitor SB 202190 reduced IBT 9631-induced H2AX activation. Both IBT 9631
      and T-2 induced activation of Chk2 and H2AX after 3 h. The ATM inhibitor KU
      55933, as well as transfection of cells with ATM siRNA, reduced this activation,
      suggesting a partial role for ATM as upstream activator for Chk2 and H2AX. In
      conclusion, activation of Chk2 and H2AX correlated with spore- and toxin-induced
      apoptosis. For IBT 9631 and satratoxin G, additional factors may be involved in
      triggering apoptosis, most notably p38 activation.

PMID- 20150442
TI  - A stratified redox model for the Ediacaran ocean.
AB  - The Ediacaran Period (635 to 542 million years ago) was a time of fundamental
      environmental and evolutionary change, culminating in the first appearance of
      macroscopic animals. Here, we present a detailed spatial and temporal record of
      Ediacaran ocean chemistry for the Doushantuo Formation in the Nanhua Basin, South
      China. We find evidence for a metastable zone of euxinic (anoxic and sulfidic)
      waters impinging on the continental shelf and sandwiched within ferruginous
      [Fe(II)-enriched] deep waters. A stratified ocean with coeval oxic, sulfidic, and
      ferruginous zones, favored by overall low oceanic sulfate concentrations, was
      maintained dynamically throughout the Ediacaran Period. Our model reconciles
      seemingly conflicting geochemical redox conditions proposed previously for
      Ediacaran deep oceans and helps to explain the patchy temporal record of early
      metazoan fossils.

PMID- 20150443
TI  - Light-controlled self-assembly of semiconductor nanoparticles into twisted
      ribbons.
AB  - The collective properties of nanoparticles manifest in their ability to self
      organize into complex microscale structures. Slow oxidation of tellurium ions in
      cadmium telluride (CdTe) nanoparticles results in the assembly of 1- to 4
      micrometer-long flat ribbons made of several layers of individual cadmium sulfide
      (CdS)/CdTe nanocrystals. Twisting of the ribbons with an equal distribution of
      left and right helices was induced by illumination with visible light. The pitch
      lengths (250 to 1500 nanometers) varied with illumination dose, and the twisting
      was associated with the relief of mechanical shear stress in assembled ribbons
      caused by photooxidation of CdS. Unusual shapes of multiparticle assemblies, such
      as ellipsoidal clouds, dog-bone agglomerates, and ribbon bunches, were observed
      as intermediate stages. Computer simulations revealed that the balance between
      attraction and electrostatic repulsion determines the resulting geometry and
      dimensionality of the nanoparticle assemblies.

PMID- 20150445
TI  - Intellectual property. Fixing the legal framework for pharmaceutical research.

PMID- 20150444
TI  - Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release.
AB  - Synaptic vesicle fusion in brain synapses occurs in phases that are either
      tightly coupled to action potentials (synchronous), immediately following action
      potentials (asynchronous), or as stochastic events in the absence of action
      potentials (spontaneous). Synaptotagmin-1, -2, and -9 are vesicle-associated Ca2+
      sensors for synchronous release. Here we found that double C2 domain (Doc2)
      proteins act as Ca2+ sensors to trigger spontaneous release. Although Doc2
      proteins are cytosolic, they function analogously to synaptotagmin-1 but with a
      higher Ca2+ sensitivity. Doc2 proteins bound to N-ethylmaleimide-sensitive factor
      attachment receptor (SNARE) complexes in competition with synaptotagmin-1. Thus,
      different classes of multiple C2 domain-containing molecules trigger synchronous
      versus spontaneous fusion, which suggests a general mechanism for synaptic
      vesicle fusion triggered by the combined actions of SNAREs and multiple C2 domain
      containing proteins.

PMID- 20150447
TI  - Significant acidification in major Chinese croplands.
AB  - Soil acidification is a major problem in soils of intensive Chinese agricultural
      systems. We used two nationwide surveys, paired comparisons in numerous
      individual sites, and several long-term monitoring-field data sets to evaluate
      changes in soil acidity. Soil pH declined significantly (P < 0.001) from the
      1980s to the 2000s in the major Chinese crop-production areas. Processes related
      to nitrogen cycling released 20 to 221 kilomoles of hydrogen ion (H+) per hectare
      per year, and base cations uptake contributed a further 15 to 20 kilomoles of H+
      per hectare per year to soil acidification in four widespread cropping systems.
      In comparison, acid deposition (0.4 to 2.0 kilomoles of H+ per hectare per year)
      made a small contribution to the acidification of agricultural soils across
      China.

PMID- 20150448
TI  - Potassium homeostasis and renin-angiotensin-aldosterone system inhibitors.
AB  - Inhibition of the renin-angiotensin-aldosterone system (RAAS) is a key strategy
      in treating hypertension and cardiovascular and renal diseases. However, RAAS
      inhibitors (angiotensin-converting enzyme inhibitors, angiotensin receptor
      blockers, aldosterone receptor antagonists, and direct renin inhibitors) increase
      the risk of hyperkalemia (serum potassium >5.5 mmol/L). This review evaluates the
      effects on serum potassium levels of RAAS inhibitors. Using PubMed, we searched
      for clinical trials published up to December 2008 assessing the effects on serum
      potassium levels of angiotensin-converting enzyme inhibitors, angiotensin
      receptor blockers, aldosterone receptor antagonists, and direct renin inhibitors,
      alone and in combination, in patients with hypertension, heart failure (HF), or
      chronic kidney disease (CKD); 39 studies were identified. In patients with
      hypertension without risk factors for hyperkalemia, the incidence of hyperkalemia
      with RAAS inhibitor monotherapy is low (< or =2%), whereas rates are higher with
      dual RAAS inhibition ( approximately 5%). The incidence of hyperkalemia is also
      increased in patients with HF or CKD (5% to 10%). However, increases in serum
      potassium levels are small ( approximately 0.1 to 0.3 mmol/L), and rates of study
      discontinuation due to hyperkalemia are low, even in high-risk patient groups (1%
      to 5%). Patients with HF or CKD are at greater risk of hyperkalemia with RAAS
      inhibitors than those without these conditions. However, the absolute changes in
      serum potassium are generally small and unlikely to be clinically significant.
      Moreover, these patients are likely to derive benefit from RAAS inhibition.
      Rather than denying them an effective treatment, electrolyte levels should be
      closely monitored in these patients.

PMID- 20150446
TI  - Dark matter search results from the CDMS II experiment.
AB  - Astrophysical observations indicate that dark matter constitutes most of the mass
      in our universe, but its nature remains unknown. Over the past decade, the
      Cryogenic Dark Matter Search (CDMS II) experiment has provided world-leading
      sensitivity for the direct detection of weakly interacting massive particle
      (WIMP) dark matter. The final exposure of our low-temperature germanium particle
      detectors at the Soudan Underground Laboratory yielded two candidate events, with
      an expected background of 0.9 +/- 0.2 events. This is not statistically
      significant evidence for a WIMP signal. The combined CDMS II data place the
      strongest constraints on the WIMP-nucleon spin-independent scattering cross
      section for a wide range of WIMP masses and exclude new parameter space in
      inelastic dark matter models.

PMID- 20150449
TI  - A novel WT1 gene mutation in a three-generation family with progressive isolated
      focal segmental glomerulosclerosis.
AB  - BACKGROUND AND OBJECTIVES: Wilms tumor-suppressor gene-1 (WT1) plays a key role
      in kidney development and function. WT1 mutations usually occur in exons 8 and 9
      and are associated with Denys-Drash, or in intron 9 and are associated with
      Frasier syndrome. However, overlapping clinical and molecular features have been
      reported. Few familial cases have been described, with intrafamilial variability.
      Sporadic cases of WT1 mutations in isolated diffuse mesangial sclerosis or focal
      segmental glomerulosclerosis have also been reported. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Molecular analysis of WT1 exons 8 and 9 was carried
      out in five members on three generations of a family with late-onset isolated
      proteinuria. The effect of the detected amino acid substitution on WT1 protein's
      structure was studied by bioinformatics tools. RESULTS: Three family members
      reached end-stage renal disease in full adulthood. None had genital abnormalities
      or Wilms tumor. Histologic analysis in two subjects revealed focal segmental
      glomerulosclerosis. The novel sequence variant c.1208G>A in WT1 exon 9 was
      identified in all of the affected members of the family. CONCLUSIONS: The lack of
      Wilms tumor or other related phenotypes suggests the expansion of WT1 gene
      analysis in patients with focal segmental glomerulosclerosis, regardless of age
      or presence of typical Denys-Drash or Frasier syndrome clinical features.
      Structural analysis of the mutated protein revealed that the mutation hampers
      zinc finger-DNA interactions, impairing target gene transcription. This finding
      opens up new issues about WT1 function in the maintenance of the complex gene
      network that regulates normal podocyte function.

PMID- 20150451
TI  - Reaping benefits of crop research.

PMID- 20150452
TI  - Particle physics. New delay of Large Hadron Collider might not keep its rival on
      the job.

PMID- 20150450
TI  - Pharmacokinetics and pharmacodynamics of intensified versus standard dosing of
      mycophenolate sodium in renal transplant patients.
AB  - BACKGROUND AND OBJECTIVES: Adequate early mycophenolic acid (MPA) exposure is an
      important determinant for effective rejection prophylaxis. This pharmacokinetic
      study investigated whether an intensified dosing regimen of enteric-coated
      mycophenolate sodium (EC-MPS) could achieve higher mycophenolic acid (MPA)
      exposure early after transplantation versus a standard dosing regimen. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: De novo kidney transplant recipients (n =
      75) who were treated with basiliximab induction and cyclosporine were randomly
      assigned to receive EC-MPS as either standard dosing (1440 mg/d; n = 37) or
      intensified dosing (days 0 through 14: 2880 mg/d; days 15 through 42: 2160 mg/d;
      followed by 1440 mg/d; n = 38). Full 12-hour pharmacokinetic and pharmacodynamic
      profiles were taken at six time points during the first 3 months. Exploratory
      analysis of inosine monophosphate dehydrogenase (IMPDH) activity was also
      performed for better understanding of the pharmacokinetic-pharmacodynamic
      relationship between MPA exposure and IMPDH activity in the early
      posttransplantation period. Preliminary efficacy parameters, safety, and
      tolerability were assessed. RESULTS: Exposure to MPA was significantly higher on
      days 3 and 10 after transplantation in the intensified versus standard EC-MPS
      group, with 52.9 versus 22.2% (P < 0.05) of patients reaching MPA exposure >40
      mg/h per L in the first week. The intensified regimen resulted in significantly
      lower IMPDH activity on day 3 after transplantation, and the overall safety was
      comparable for both groups. CONCLUSIONS: These pharmacokinetic and safety data
      support further research on the hypothesis that early adequate MPA exposure could
      improve clinical outcome.

PMID- 20150453
TI  - India. After acrimonious debate, India rejects GM eggplant.

PMID- 20150454
TI  - U.S. science policy. Bement to leave NSF before term ends.

PMID- 20150455
TI  - Newsmaker interview. IPCC seeks 'broader community engagement' to correct errors.
      Interview by Eli Kintisch.

PMID- 20150458
TI  - Psychiatry. DSM-V at a glance.

PMID- 20150459
TI  - Psychiatry. Proposed revisions to psychiatry's canon unveiled.

PMID- 20150460
TI  - Immunology. Replacing an immune system gone haywire.

PMID- 20150461
TI  - Newsmaker interview. Down-to-earth science fiction. Interview by Elizabeth
      Pennisi.

PMID- 20150462
TI  - Society for Integrative and Comparative Biology, 3-7 January 2010, Seattle,
      Washington. Rattan stuck in a growth mode.

PMID- 20150463
TI  - Society for Integrative and Comparative Biology, 3-7 January 2010, Seattle,
      Washington. Racing crash-happy cockroaches.

PMID- 20150464
TI  - Society for Integrative and Comparative Biology, 3-7 January 2010, Seattle,
      Washington. Koalas calling.

PMID- 20150465
TI  - Science and society. Lights! Camera! Science?

PMID- 20150466
TI  - Carbon calculations to consider.

PMID- 20150467
TI  - Stop listening to scientists?

PMID- 20150469
TI  - Economics. Sustainability and global seafood.

PMID- 20150470
TI  - Cell biology. Propelling progeny.

PMID- 20150471
TI  - Chemistry. Ultracold chemistry.

PMID- 20150473
TI  - Climate change. Ice age rhythms.

PMID- 20150472
TI  - Chemistry. CO prefers the aisle seat.

PMID- 20150474
TI  - Genetics. Genetic control of hotspots.

PMID- 20150475
TI  - Microbiology. Feasting on minerals.

PMID- 20150476
TI  - Chemistry. Radical ligands confer nobility on base-metal catalysts.

PMID- 20150477
TI  - Food security. Feeding the future. Introduction.

PMID- 20150478
TI  - From one farmer, hope--and reason for worry.

PMID- 20150479
TI  - Getting more drops to the crops.

PMID- 20150480
TI  - China's push to add by subtracting fertilizer.

PMID- 20150481
TI  - Sowing the seeds for the ideal crop.

PMID- 20150482
TI  - Armed and dangerous.

PMID- 20150483
TI  - Holding back a torrent of rats.

PMID- 20150484
TI  - Spoiling for a fight with mold.

PMID- 20150486
TI  - What it takes to make that meal.

PMID- 20150485
TI  - Dialing up knowledge--and harvests.

PMID- 20150487
TI  - Could less meat mean more food?

PMID- 20150488
TI  - For more protein, filet of cricket.

PMID- 20150489
TI  - Breeding technologies to increase crop production in a changing world.
AB  - To feed the several billion people living on this planet, the production of high
      quality food must increase with reduced inputs, but this accomplishment will be
      particularly challenging in the face of global environmental change. Plant
      breeders need to focus on traits with the greatest potential to increase yield.
      Hence, new technologies must be developed to accelerate breeding through
      improving genotyping and phenotyping methods and by increasing the available
      genetic diversity in breeding germplasm. The most gain will come from delivering
      these technologies in developing countries, but the technologies will have to be
      economically accessible and readily disseminated. Crop improvement through
      breeding brings immense value relative to investment and offers an effective
      approach to improving food security.

PMID- 20150491
TI  - Measuring food insecurity.
AB  - Food security is a growing concern worldwide. More than 1 billion people are
      estimated to lack sufficient dietary energy availability, and at least twice that
      number suffer micronutrient deficiencies. Because indicators inform action, much
      current research focuses on improving food insecurity measurement. Yet estimated
      prevalence rates and patterns remain tenuous because measuring food security, an
      elusive concept, remains difficult.

PMID- 20150490
TI  - Smart investments in sustainable food production: revisiting mixed crop-livestock
      systems.
AB  - Farmers in mixed crop-livestock systems produce about half of the world's food.
      In small holdings around the world, livestock are reared mostly on grass, browse,
      and nonfood biomass from maize, millet, rice, and sorghum crops and in their turn
      supply manure and traction for future crops. Animals act as insurance against
      hard times and supply farmers with a source of regular income from sales of milk,
      eggs, and other products. Thus, faced with population growth and climate change,
      small-holder farmers should be the first target for policies to intensify
      production by carefully managed inputs of fertilizer, water, and feed to minimize
      waste and environmental impact, supported by improved access to markets, new
      varieties, and technologies.

PMID- 20150492
TI  - Precision agriculture and food security.
AB  - Precision agriculture comprises a set of technologies that combines sensors,
      information systems, enhanced machinery, and informed management to optimize
      production by accounting for variability and uncertainties within agricultural
      systems. Adapting production inputs site-specifically within a field and
      individually for each animal allows better use of resources to maintain the
      quality of the environment while improving the sustainability of the food supply.
      Precision agriculture provides a means to monitor the food production chain and
      manage both the quantity and quality of agricultural produce.

PMID- 20150493
TI  - African Green Revolution needn't be a mirage.
AB  - Africa missed out on the scientific breakthroughs that revolutionized agriculture
      in Asia. However, with locally developed and locally relevant technologies, a
      built-up human and institutional capacity, and supportive national policy and
      leadership, an African Green Revolution can be a reality.

PMID- 20150494
TI  - Radically rethinking agriculture for the 21st century.
AB  - Population growth, arable land and fresh water limits, and climate change have
      profound implications for the ability of agriculture to meet this century's
      demands for food, feed, fiber, and fuel while reducing the environmental impact
      of their production. Success depends on the acceptance and use of contemporary
      molecular techniques, as well as the increasing development of farming systems
      that use saline water and integrate nutrient flows.

PMID- 20150495
TI  - Resonance fluorescence of a single artificial atom.
AB  - An atom in open space can be detected by means of resonant absorption and
      reemission of electromagnetic waves, known as resonance fluorescence, which is a
      fundamental phenomenon of quantum optics. We report on the observation of
      scattering of propagating waves by a single artificial atom. The behavior of the
      artificial atom, a superconducting macroscopic two-level system, is in a
      quantitative agreement with the predictions of quantum optics for a pointlike
      scatterer interacting with the electromagnetic field in one-dimensional open
      space. The strong atom-field interaction as revealed in a high degree of
      extinction of propagating waves will allow applications of controllable
      artificial atoms in quantum optics and photonics.

PMID- 20150496
TI  - Spin-dependent quantum interference within a single magnetic nanostructure.
AB  - Quantum interference is a coherent quantum phenomenon that takes place in
      confined geometries. Using spin-polarized scanning tunneling microscopy, we found
      that quantum interference of electrons causes spatial modulation of spin
      polarization within a single magnetic nanostructure. We observed changes in both
      the sign and magnitude of the spin polarization on a subnanometer scale. A
      comparison of our experimental results with ab initio calculations shows that at
      a given energy, the modulation of the spin polarization can be ascribed to the
      difference between the spatially modulated local density of states of the
      majority spin and the nonmodulated minority spin contribution.

PMID- 20150497
TI  - Multiple functional groups of varying ratios in metal-organic frameworks.
AB  - We show that metal-organic frameworks (MOFs) can incorporate a large number of
      different functionalities on linking groups in a way that mixes the linker,
      rather than forming separate domains. We made complex MOFs from 1,4
      benzenedicarboxylate (denoted by "A" in this work) and its derivatives -NH2, -Br,
      -(Cl)2, -NO2, -(CH3)2, -C4H4, -(OC3H5)2, and -(OC7H7)2 (denoted by "B" to "I,"
      respectively) to synthesize 18 multivariate (MTV) MOF-5 type structures that
      contain up to eight distinct functionalities in one phase. The backbone (zinc
      oxide and phenylene units) of these structures is ordered, but the distribution
      of functional groups is disordered. The complex arrangements of several
      functional groups within the pores can lead to properties that are not simply
      linear sums of those of the pure components. For example, a member of this
      series, MTV-MOF-5-EHI, exhibits up to 400% better selectivity for carbon dioxide
      over carbon monoxide compared with its best same-link counterparts.

PMID- 20150498
TI  - Break-up of stepped platinum catalyst surfaces by high CO coverage.
AB  - Stepped single-crystal surfaces are viewed as models of real catalysts, which
      consist of small metal particles exposing a large number of low-coordination
      sites. We found that stepped platinum (Pt) surfaces can undergo extensive and
      reversible restructuring when exposed to carbon monoxide (CO) at pressures above
      0.1 torr. Scanning tunneling microscopy and photoelectron spectroscopy studies
      under gaseous environments near ambient pressure at room temperature revealed
      that as the CO surface coverage approaches 100%, the originally flat terraces of
      (557) and (332) oriented Pt crystals break up into nanometer-sized clusters and
      revert to the initial morphology after pumping out the CO gas. Density functional
      theory calculations provide a rationale for the observations whereby the creation
      of increased concentrations of low-coordination Pt edge sites in the formed
      nanoclusters relieves the strong CO-CO repulsion in the highly compressed
      adsorbate film. This restructuring phenomenon has important implications for
      heterogeneous catalytic reactions.

PMID- 20150499
TI  - Quantum-state controlled chemical reactions of ultracold potassium-rubidium
      molecules.
AB  - How does a chemical reaction proceed at ultralow temperatures? Can simple quantum
      mechanical rules such as quantum statistics, single partial-wave scattering, and
      quantum threshold laws provide a clear understanding of the molecular reactivity
      under a vanishing collision energy? Starting with an optically trapped near
      quantum-degenerate gas of polar 40K87Rb molecules prepared in their absolute
      ground state, we report experimental evidence for exothermic atom-exchange
      chemical reactions. When these fermionic molecules were prepared in a single
      quantum state at a temperature of a few hundred nanokelvin, we observed p-wave
      dominated quantum threshold collisions arising from tunneling through an angular
      momentum barrier followed by a short-range chemical reaction with a probability
      near unity. When these molecules were prepared in two different internal states
      or when molecules and atoms were brought together, the reaction rates were
      enhanced by a factor of 10 to 100 as a result of s-wave scattering, which does
      not have a centrifugal barrier. The measured rates agree with predicted universal
      loss rates related to the two-body van der Waals length.

PMID- 20150500
TI  - Low-frequency modes of aqueous alkali halide solutions: glimpsing the hydrogen
      bonding vibration.
AB  - The solvation of ions in aqueous media is a fundamental process in biology and
      chemistry. Here, we report direct time-domain observations of the hydrogen bond
      vibrational mode formed between a halide ion (chloride, bromide, or iodide) and
      the surrounding water molecules. The frequency of the hydrogen bond mode is
      sensitive to both the atomic weight and the concentration of the ion. The peak
      frequencies fall in the 125 to 175 wave-number range, a spectral region accessed
      through time-domain polarization-resolved coherent Raman scattering using a
      diffractive optic method. The polarized Raman response observed is discussed in
      terms of the structure of the anion's solvation shell and modeled through
      calculations on water chloride clusters.

PMID- 20150501
TI  - Sea-level highstand 81,000 years ago in Mallorca.
AB  - Global sea level and Earth's climate are closely linked. Using speleothem
      encrustations from coastal caves on the island of Mallorca, we determined that
      western Mediterranean relative sea level was approximately 1 meter above modern
      sea level approximately 81,000 years ago during marine isotope stage (MIS) 5a.
      Although our findings seemingly conflict with the eustatic sea-level curve of far
      field sites, they corroborate an alternative view that MIS 5a was at least as ice
      free as the present, and they challenge the prevailing view of MIS 5 sea-level
      history and certain facets of ice-age theory.

PMID- 20150502
TI  - Vibrio cholerae VpsT regulates matrix production and motility by directly sensing
      cyclic di-GMP.
AB  - Microorganisms can switch from a planktonic, free-swimming life-style to a
      sessile, colonial state, called a biofilm, which confers resistance to
      environmental stress. Conversion between the motile and biofilm life-styles has
      been attributed to increased levels of the prokaryotic second messenger cyclic di
      guanosine monophosphate (c-di-GMP), yet the signaling mechanisms mediating such a
      global switch are poorly understood. Here we show that the transcriptional
      regulator VpsT from Vibrio cholerae directly senses c-di-GMP to inversely control
      extracellular matrix production and motility, which identifies VpsT as a master
      regulator for biofilm formation. Rather than being regulated by phosphorylation,
      VpsT undergoes a change in oligomerization on c-di-GMP binding.

PMID- 20150504
TI  - Recurrent capillary leak syndrome following bortezomib therapy in a patient with
      relapsed myeloma.
AB  - OBJECTIVE: To describe the first case of bortezomib-induced capillary leak
      syndrome (CLS), a rare but potentially life-threatening condition characterized
      by the shift of intravascular fluid and protein to the interstitial space. CASE
      SUMMARY: A 65-year-old female with relapsed multiple myeloma developed fluid
      retention, ascites, and general anasarca following bortezomib administration (1.3
      mg/m(2) on days 1, 4, 8, and 11). Aggressive albumin infusion and loop diuretics
      did not lead to improvement and the patient received 2 sessions of hemodialysis
      for pulmonary edema. Although the bortezomib dose was reduced (0.7 mg/m(2) on
      days 1, 4, and 11) for the second cycle, CLS recurred after treatment.
      Dexamethasone was given along with bortezomib in the third cycle and subsequent
      CLS was prevented. The patient's multiple myeloma responded partially to the
      treatment, but the patient later died from cardiac amyloidosis. DISCUSSION:
      Bortezomib is associated with several well-known adverse effects, such as
      peripheral neuropathy, thrombocytopenia, and gastrointestinal complications. CLS
      has not previously been reported to be associated with bortezomib. In this case,
      CLS developed twice after the patient received bortezomib treatment. The severity
      of CLS was dose-dependent and this adverse effect was preventable by concomitant
      use of steroids; this clearly demonstrated the close relationship between CLS and
      bortezomib in this patient. Using the Naranjo probability scale, the occurrence
      of CLS related to bortezomib treatment was probable. CONCLUSIONS: Our report
      demonstrates CLS as an unusual adverse effect of bortezomib. As bortezomib use
      may become more common, clinicians should be aware of this novel but potentially
      life-threatening adverse effect. Based on our experience, timely management with
      steroids is important in dealing with this complication.

PMID- 20150505
TI  - Stability of extemporaneously prepared rufinamide oral suspensions.
AB  - BACKGROUND: Rufinamide is an oral antiepileptic drug indicated for adjunctive
      therapy in treating generalized seizures associated with Lennox-Gastaut syndrome.
      Currently, rufinamide is available as 200-mg and 400-mg tablets. A liquid dosage
      form does not exist at the present time. Lack of a suspension formulation may
      present an administration problem for many children and adults who are unable to
      swallow tablets. The availability of a liquid dosage form will provide an easy
      and accurate way to measure and administer the medication. OBJECTIVE: To
      determine the stability of both sugar-containing and sugar-free rufinamide
      suspensions over a 90-day period. METHODS: A suspension of rufinamide 40 mg/mL
      was prepared by grinding twelve 400-mg tablets of rufinamide tablets in a glass
      mortar. Sixty milliliters of Ora-Plus and 60 mL of either Ora-Sweet or Ora-Sweet
      SF (sugar free) were mixed and added to the powder to make a final volume of 120
      mL. Three identical samples of each formulation were prepared and placed in 60-mL
      amber plastic bottles and were stored at room temperature. A 1-mL sample was
      withdrawn from each of the 6 bottles with a micropipette immediately after
      preparation and at 7, 14, 28, 56, and 90 days. After further dilution to an
      expected concentration of 0.4 mg/mL, the samples were assayed using high
      performance liquid chromatography. Stability was defined as the retention of at
      least 90% of the initial concentration. RESULTS: At least 90% of the initial
      rufinamide concentration remained throughout the 90-day study period in both
      preparations. There were no detectable changes in color, odor, taste, and pH and
      no visible microbial growth. CONCLUSIONS: Extemporaneously compounded suspensions
      of rufinamide 40 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet or Ora-Sweet SF
      were stable for at least 90 days when stored in 59-mL amber polypropylene plastic
      bottles at room temperature.

PMID- 20150506
TI  - Increased clinical failures when treating acute otitis media with macrolides: a
      meta-analysis.
AB  - BACKGROUND: Macrolide antibiotics are often used to treat children with acute
      otitis media (AOM); however, the 2004 American Academy of Pediatrics (AAP) and
      American Academy of Family Physicians guidelines recommend against their use in
      patients without history of a type I allergic reaction to penicillins. OBJECTIVE:
      To evaluate via meta-analysis the comparative efficacy of amoxicillin or
      amoxicillin/clavulanate to that of macrolide antibiotics in the treatment of
      children with AOM. METHODS: A systematic literature search of MEDLINE, EMBASE,
      and International Pharmaceutical Abstracts was conducted from the earliest
      available date through September 2008. We used the following MeSH and key words:
      amoxicillin, amoxicillin/clavulanate, Augmentin, azithromycin, ceftriaxone,
      clarithromycin, macrolides, AND media, otitis media, and effusion. Included
      studies were randomized, blinded, and controlled trials evaluating guideline
      recommended antibiotics (amoxicillin or amoxicillin/clavulanate) compared to
      macrolide antibiotics (azithromycin or clarithromycin) in AOM in children. The
      primary outcome assessed was clinical failure measured between days 10 and 16
      after starting antibiotic therapy. Results are reported as relative risks (RRs)
      with 95% confidence intervals and were calculated using a random-effects model.
      RESULTS: A total of 10 trials (N = 2766) evaluating children 6 months-15 years
      old were included in the meta-analysis. Upon meta-analysis, the use of macrolide
      antibiotics was associated with an increased risk of clinical failure (RR 1.31
      [95% CI 1.07 to 1.60]; p = 0.008) corresponding to a number needed to harm of 32.
      Upon safety analysis, rates of any adverse reaction (RR 0.74 [95% CI 0.60 to
      0.90]; p = 0.003) and diarrhea (RR 0.41 [95% CI 0.32 to 0.52]; p < 0.0001) were
      significantly lower in the macrolide group. CONCLUSIONS: The meta-analysis
      suggests that patients treated with macrolides for AOM may be more likely to have
      clinical failures. As such, it supports the current AAP AOM recommendation that
      macrolides be reserved for patients who can not receive amoxicillin or
      amoxicillin/clavulanate.

PMID- 20150507
TI  - Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta
      analysis and qualitative review.
AB  - OBJECTIVE: To evaluate the analgesic and antipyretic efficacy and safety of
      ibuprofen compared to acetaminophen in children and adults. DATA SOURCES:
      Literature searches were performed using PubMed/MEDLINE (through August 2009) and
      EMBASE (through January 2008) and were restricted to the English language. In
      PubMed/MEDLINE, search terms used were ibuprofen, acetaminophen, paracetamol,
      clinical trials, and randomized controlled trials. EMBASE search terms included
      ibuprofen and acetaminophen, restricted to human and clinical trials. STUDY
      SELECTION AND DATA EXTRACTION: All English-language articles identified from the
      data sources were reviewed. Multiple review articles were studied for any
      pertinent references and this yielded additional articles. Only articles that
      directly compared ibuprofen and acetaminophen were eligible for this review. DATA
      SYNTHESIS: Eighty-five studies that directly compared ibuprofen to acetaminophen
      were identified; 54 contained analgesic efficacy data, 35 contained
      antipyretic/temperature reduction data, and 66 contained safety data (some
      articles contained more than 1 type of data). Qualitative review of the
      literature revealed that, for the most part, ibuprofen was more efficacious than
      acetaminophen for the treatment of pain and fever in both pediatric and adult
      populations, and that these 2 drugs were equally safe. Meta-analyses on the
      subset of randomized clinical trial articles that reported sufficient
      quantitative information to calculate either an odds ratio (adverse event [AE])
      or standardized mean difference (pain and fever) confirmed the qualitative
      results for adult (standardized mean difference [SMD] 0.69; 95% CI 0.57 to 0.81)
      and pediatric (SMD 0.28; 95% CI 0.10 to 0.46) pain at 2 hours postdose and
      pediatric fever (SMD 0.26; 95% CI 0.10 to 0.41) at 4 hours postdose. Conclusions
      regarding adult fever/temperature reduction could not be made due to a lack of
      evaluable data. The combined odds ratio for the proportion of adult subjects
      experiencing at least 1 AE slightly favored ibuprofen; however, the difference
      was not statistically significant (1.12; 95% CI 1.00 to 1.25). No significant
      difference between drugs in AE incidence was found for pediatric patients (0.82;
      95% CI 0.60 to 1.12). CONCLUSIONS: Ibuprofen is as or more efficacious than
      acetaminophen for the treatment of pain and fever in adult and pediatric
      populations and is equally safe.

PMID- 20150508
TI  - Structure of sterol aliphatic chains affects yeast cell shape and cell fusion
      during mating.
AB  - Under mating conditions, yeast cells adopt a characteristic pear-shaped
      morphology, called a "shmoo," as they project a cell extension toward their
      mating partners. Mating partners make contact at their shmoo tips, dissolve the
      intervening cell wall, and fuse their plasma membranes. We identified mutations
      in ERG4, encoding the enzyme that catalyzes the last step of ergosterol
      biosynthesis, that impair both shmoo formation and cell fusion. Upon pheromone
      treatment, erg4Delta mutants polarized growth, lipids, and proteins involved in
      mating but did not form properly shaped shmoos and fused with low efficiency.
      Supplementation with ergosterol partially suppressed the shmooing defect but not
      the cell fusion defect. By contrast, removal of the Erg4 substrate ergosta
      5,7,22,24(28)-tetraenol, which accumulates in erg4Delta mutant cells and contains
      an extra double bond in the aliphatic chain of the sterol, restored both shmooing
      and cell fusion to wild-type levels. Thus, a two-atom change in the aliphatic
      moiety of ergosterol is sufficient to obstruct cell shape remodeling and cell
      fusion.

PMID- 20150509
TI  - In vivo actin cross-linking induced by Vibrio cholerae type VI secretion system
      is associated with intestinal inflammation.
AB  - Type VI secretion systems (T6SSs) have recently been recognized as potential
      virulence determinants of many Gram-negative bacterial pathogens. Although
      mechanistic studies are lacking, T6SS-dependent phenotypes can be observed in
      various animal models of infection. Presumably translocation of T6SS effectors
      into target cells is involved in virulence, but few such effectors have been
      identified. A hallmark of T6SS function is the in vitro secretion of Hcp and VgrG
      proteins, which are thought to form part of an extracellular secretion apparatus.
      One well-characterized effector domain is the C-terminal actin cross-linking
      domain (ACD) of the VgrG-1 protein, constitutively secreted by the T6SS of Vibrio
      cholerae strain V52. Previous work indicated that translocation of VgrG-1
      occurred only after endocytic uptake of bacteria into host cells. VgrG-1-induced
      actin cross-linking impaired phagocytic activity of host cells, eventually
      causing cell death. To determine whether V. cholerae T6SS is functional during
      animal infection, derivatives of V52 were used to infect infant mice. In this
      infection model a diarrheal response occurred, and actin cross-linking could be
      detected. These host responses were dependent on a functional T6SS and on the ACD
      of VgrG-1. Gene expression and histologic studies showed innate immune activation
      and immune cell infiltration in the intestinal lumen. The T6SS-dependent
      inflammatory response was also associated with increased recovery of V. cholerae
      from the intestine. We conclude that the T6SS of V52 induces an inflammatory
      diarrhea that facilitates replication of V. cholerae within the intestine.

PMID- 20150510
TI  - Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and
      apoptosis via a non-canonical p38alpha MAPK pathway.
AB  - Patients with primary (AL) cardiac amyloidosis suffer from progressive
      cardiomyopathy with a median survival of less than 8 months and a 5-year survival
      of <10%. Contributing to this poor prognosis is the fact that these patients
      generally do not tolerate standard heart failure therapies. The molecular
      mechanisms underlying this deadly form of heart disease remain unclear. Although
      interstitial amyloid fibril deposition of Ig light chain proteins is a major
      cause of cardiac dysfunction in AL cardiac amyloidosis, we have previously shown
      that amyloid precursor proteins directly impair cardiac function at the cellular
      and isolated organ levels, independent of fibril formation. In this study, we
      report that amyloidogenic light chain (AL-LC) proteins provoke oxidative stress,
      cellular dysfunction, and apoptosis in isolated adult cardiomyocytes through
      activation of p38 mitogen-activated protein kinase (MAPK). AL-LC-induced p38
      activation was found to be independent of the upstream MAPK kinase, MKK3/6, and
      instead depends upon transforming growth factor-beta-activated protein kinase-1
      binding protein-1 (TAB1)-mediated p38alpha MAPK autophosphorylation. Treatment of
      cardiomyocytes with SB203580, a selective p38 MAPK inhibitor, significantly
      attenuated AL-LC-induced oxidative stress, cellular dysfunction, and apoptosis.
      Our data provide a unique mechanistic insight into the pathogenesis of AL-LC
      cardiac toxicity and suggest that TAB1-mediated p38alpha MAPK autophosphorylation
      may serve as an important event leading to cardiac dysfunction and subsequent
      heart failure.

PMID- 20150511
TI  - Lower number of cerebellar Purkinje neurons in psychosis is associated with
      reduced reelin expression.
AB  - Reelin is an extracellular matrix protein synthesized in cerebellar granule cells
      that plays an important role in Purkinje cell positioning during cerebellar
      development and in modulating adult synaptic function. In the cerebellum of
      schizophrenia (SZ) and bipolar (BP) disorder patients, there is a marked decrease
      ( approximately 50%) of reelin expression. In this study we measured Purkinje
      neuron density in the Purkinje cell layer of cerebella of 13 SZ and 17 BP
      disorder patients from the McLean 66 Cohort Collection, Harvard Brain Tissue
      Resource Center. The mean number of Purkinje neurons (linear density, neurons per
      millimeter) was 20% lower in SZ and BP disorder patients compared with
      nonpsychiatric subjects (NPS; n = 24). This decrease of Purkinje neuron linear
      density was unrelated to postmortem interval, pH, drugs of abuse, or to the
      presence, dose, or duration of antipsychotic medications. A comparative study in
      the cerebella of heterozygous reeler mice (HRM), in which reelin expression is
      down-regulated by approximately 50%, showed a significant loss in the number of
      Purkinje cells in HRM (10-15%) compared with age-matched (3-9 months) wild-type
      mice. This finding suggests that lack of reelin impairs GABAergic Purkinje neuron
      expression and/or positioning during cerebellar development.

PMID- 20150512
TI  - Pharmaceutical modulation of canonical Wnt signaling in multipotent stromal cells
      for improved osteoinductive therapy.
AB  - Human mesenchymal stem cells (hMSCs) from bone marrow are regarded as putative
      osteoblast progenitors in vivo and differentiate into osteoblasts in vitro.
      Positive signaling by the canonical wingless (Wnt) pathway is critical for the
      differentiation of MSCs into osteoblasts. In contrast, activation of the
      peroxisome proliferator-activated receptor-gamma (PPARgamma)-mediated pathway
      results in adipogenesis. We therefore compared the effect of glycogen-synthetase
      kinase-3beta (GSK3beta) inhibitors and PPARgamma inhibitors on osteogenesis by
      hMSCs. Both compounds altered the intracellular distribution of beta-catenin and
      GSK3beta in a manner consistent with activation of Wnt signaling. With osteogenic
      supplements, the GSK3beta inhibitor 6-bromo-indirubin-3'-oxime (BIO) and the
      PPARgamma inhibitor GW9662 (GW) enhanced early osteogenic markers, alkaline
      phosphatase (ALP), and osteoprotegerin (OPG) by hMSCs and transcriptome analysis
      demonstrated up-regulation of genes encoding bone-related structural proteins. At
      higher doses of the inhibitors, ALP levels were attenuated, but dexamethasone
      induced biomineralization was accelerated. When hMSCs were pretreated with BIO or
      GW and implanted into experimentally induced nonself healing calvarial defects,
      GW treatment substantially increased the capacity of the cells to repair the bone
      lesion, whereas BIO treatment had no significant effect. Further investigation
      indicated that unlike GW, BIO induced cell cycle inhibition in vitro.
      Furthermore, we found that GW treatment significantly reduced expression of
      chemokines that may exacerbate neutrophil- and macrophage-mediated cell
      rejection. These data suggest that use of PPARgamma inhibitors during the
      preparation of hMSCs may enhance the capacity of the cells for osteogenic
      cytotherapy, whereas adenine analogs such as BIO can adversely affect the
      viability of hMSC preparations in vitro and in vivo.

PMID- 20150513
TI  - Ketosteroid isomerase provides further support for the idea that enzymes work by
      electrostatic preorganization.
AB  - One of the best systems for exploring the origin of enzyme catalysis has been the
      reaction of ketosteroid isomerase (KSI). Studies of the binding of phenolates to
      KSI have been taken as proof that the electrostatic preorganization effect only
      makes a minor contribution to the binding of the real, multiring, transition
      state (TS). However, our simulation study has determined that the difference
      between the phenolates and the TS arises from the fact that the nonpolar state of
      the phenolate can rotate freely relative to the oxyanion hole and thus loses the
      preorganization contribution. A recent study explored the reactivity of both
      small and multiring systems and concluded that their similar reactivity
      contradicts our preorganization idea. Herein, we establish that the available
      experiments in fact provide what is perhaps the best proof and clarification of
      the preorganization idea and its crucial role in enzyme catalysis. First, we
      analyze the binding energy and the pK(a) of equilenin and identify direct
      experimental evidence for our prediction about the differential electrostatic
      stabilization of the large TS and the small phenolates. Subsequently, we show
      that the similar reactivity of the small and large systems is also due to an
      electrostatic preorganization effect but that this effect only appears in the
      intermediate state because the TS is not free to rotate. This establishes the
      electrostatic origin of enzyme catalysis. We also clarify the crucial importance
      of having a well-defined physical concept when examining catalytic effects and
      the need for quantitative tools for analyzing such effects.

PMID- 20150514
TI  - Systemic antiangiogenic activity of cationic poly-L-lysine dendrimer delays tumor
      growth.
AB  - This study describes the previously unreported intrinsic capacity of poly-L
      lysine (PLL) sixth generation (G(6)) dendrimer molecules to exhibit systemic
      antiangiogenic activity that could lead to solid tumor growth arrest. The PLL
      dendrimer-inhibited tubule formation of SVEC4-10 murine endothelial cells and
      neovascularization in the chick embryo chick chorioallantoic membrane (CAM)
      assay. Intravenous administration of the PLL-dendrimer molecules into C57BL/6
      mice inhibited vascularisation in Matrigel plugs implanted subcutaneously.
      Antiangiogenic activity was further evidenced using intravital microscopy of
      tumors grown within dorsal skinfold window chambers. Reduced vascularization of
      P22 rat sarcoma implanted in the dorsal window chamber of SCID mice was observed
      following tail vein administration (i.v.) of the PLL dendrimers. Also, the in
      vivo toxicological profile of the PLL-dendrimer molecules was shown to be safe at
      the dose regime studied. The antiangiogenic activity of the PLL dendrimer was
      further shown to be associated with significant suppression of B16F10 solid tumor
      volume and delayed tumor growth. Enhanced apoptosis/necrosis within tumors of PLL
      dendrimer-treated animals only and reduction in the number of CD31 positive cells
      were observed in comparison to protamine treatment. This study suggests that PLL
      dendrimer molecules can exhibit a systemic antiangiogenic activity that may be
      used for therapy of solid tumors, and in combination with their capacity to carry
      other therapeutic or diagnostic agents may potentially offer capabilities for the
      design of theranostic systems.

PMID- 20150515
TI  - SRD1 is involved in the auxin-mediated initial thickening growth of storage root
      by enhancing proliferation of metaxylem and cambium cells in sweetpotato (Ipomoea
      batatas).
AB  - A sweetpotato (Ipomoea batatas cv. 'Jinhongmi') MADS-box protein cDNA (SRD1) has
      been isolated from an early stage storage root cDNA library. The role of the SRD1
      gene in the formation of the storage root in sweetpotato was investigated by an
      expression pattern analysis and characterization of SRD1-overexpressing (ox)
      transgenic sweetpotato plants. Transcripts of SRD1 were detected only in root
      tissues, with the fibrous root having low levels of the transcript and the young
      storage root showing relatively higher transcript levels. SRD1 mRNA was mainly
      found in the actively dividing cells, including the vascular and cambium cells of
      the young storage root. The transcript level of SRD1 in the fibrous roots
      increased in response to 1000 muM indole-3-acetic acid (IAA) applied exogenously.
      During the early stage of storage root development, the endogenous IAA content
      and SRD1 transcript level increased concomitantly, suggesting an involvement of
      SRD1 during the early stage of the auxin-dependent development of the storage
      root. SRD1-ox sweetpotato plants cultured in vitro produced thicker and shorter
      fibrous roots than wild-type plants. The metaxylem and cambium cells of the
      fibrous roots of SRD1-ox plants showed markedly enhanced proliferation, resulting
      in the fibrous roots of these plants showing an earlier thickening growth than
      those of wild-type plants. Taken together, these results demonstrate that SRD1
      plays a role in the formation of storage roots by activating the proliferation of
      cambium and metaxylem cells to induce the initial thickening growth of storage
      roots in an auxin-dependent manner.

PMID- 20150517
TI  - The proteome map of spinach leaf peroxisomes indicates partial
      compartmentalization of phylloquinone (vitamin K1) biosynthesis in plant
      peroxisomes.
AB  - Leaf peroxisomes are fragile, low-abundance plant cell organelles that are
      difficult to isolate from one of the few plant species whose nuclear genome has
      been sequenced. Leaf peroxisomes were enriched at high purity from spinach
      (Spinacia oleracea) and approximately 100 protein spots identified from 2
      dimensional gels by a combination of liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and de novo sequencing. In addition to the predominant
      enzymes involved in photorespiration and detoxification, several minor enzymes
      were detected, underscoring the high sensitivity of the protein identification.
      The tryptic peptides of three unknown proteins shared high sequence similarity
      with Arabidopsis proteins that carry putative peroxisomal targeting signals type
      1 or 2 (PTS1/2). The apparent Arabidopsis orthologues are a short-chain alcohol
      dehydrogenase (SDRa/IBR1, At4g05530, SRL>) and two enoyl-CoA
      hydratases/isomerases (ECHIa, At4g16210, SKL>; NS/ECHId, At1g60550, RLx(5)HL).
      The peroxisomal localization of the three proteins was confirmed in vivo by
      tagging with enhanced yellow fluorescent protein (EYFP), and the targeting
      signals were identified. The single Arabidopsis isoform of naphthoate synthase
      (NS) is orthologous to MenB from cyanobacteria, which catalyses an essential
      reaction in phylloquinone biosynthesis, a pathway previously assumed to be
      entirely compartmentalized in plastids in higher plants. In an extension of a
      previous study, the present in vivo targeting data furthermore demonstrate that
      the enzyme upstream of NS, chloroplastic acyl-CoA activating enzyme isoform 14
      (AAE14, SSL>), is dually targeted to both plastids and peroxisomes. This
      proteomic study, extended by in vivo subcellular localization analyses, indicates
      a novel function for plant peroxisomes in phylloquinone biosynthesis.

PMID- 20150516
TI  - Agrobacterium tumefaciens-mediated transformation of Cleome gynandra L., a C(4)
      dicotyledon that is closely related to Arabidopsis thaliana.
AB  - In leaves of most C(4) plants, the biochemistry of photosynthesis is partitioned
      between mesophyll and bundle sheath cells. In addition, their cell biology and
      development also differs from that in C(3) plants. We have a poor understanding
      of the mechanisms that generate the cell-specific accumulation of proteins used
      in the C(4) pathway, and there are few genes that have been shown to be important
      for the cell biology and development of C(4) leaves. To facilitate functional
      analysis of C(4) photosynthesis, and to enable knowledge from Arabidopsis
      thaliana to be translated to C(4) species, an Agrobacterium tumefaciens-mediated
      transformation protocol was developed for the C(4) species Cleome gynandra. A.
      tumefaciens, harbouring the binary vector SLJ1006, was used to transfer the uidA
      gene under the control of the CaMV 35S promoter into C. gynandra. Co-incubation
      of hypocotyls or cotyledons with SLJ1006 allowed efficient transfer of DNA into
      C. gynandra, and media that allowed callus production and then shoot regeneration
      were identified. Stable transformants of C. gynandra with detectable amounts of
      beta-glucuronidase (GUS) were produced at an efficiency of 14%. When driven by
      the CaMV 35S promoter, GUS was visible in all leaf cells, whereas uidA
      translationally fused to a CgRbcS gene generated GUS accumulation specifically in
      bundle sheath cells. This transformation procedure is the first for an NAD-ME
      type C(4) plant and should significantly accelerate the analysis of mechanisms
      underlying C(4) photosynthesis.

PMID- 20150518
TI  - Metabolic profiling of Arabidopsis thaliana epidermal cells.
AB  - Metabolic phenotyping at cellular resolution may be considered one of the
      challenges in current plant physiology. A method is described which enables the
      cell type-specific metabolic analysis of epidermal cell types in Arabidopsis
      thaliana pavement, basal, and trichome cells. To achieve the required high
      spatial resolution, single cell sampling using microcapillaries was combined with
      routine gas chromatography-time of flight-mass spectrometry (GC-TOF-MS) based
      metabolite profiling. The identification and relative quantification of 117
      mostly primary metabolites has been demonstrated. The majority, namely 90
      compounds, were accessible without analytical background correction. Analyses
      were performed using cell type-specific pools of 200 microsampled individual
      cells. Moreover, among these identified metabolites, 38 exhibited differential
      pool sizes in trichomes, basal or pavement cells. The application of an
      independent component analysis confirmed the cell type-specific metabolic
      phenotypes. Significant pool size changes between individual cells were
      detectable within several classes of metabolites, namely amino acids, fatty acids
      and alcohols, alkanes, lipids, N-compounds, organic acids and polyhydroxy acids,
      polyols, sugars, sugar conjugates and phenylpropanoids. It is demonstrated here
      that the combination of microsampling and GC-MS based metabolite profiling
      provides a method to investigate the cellular metabolism of fully differentiated
      plant cell types in vivo.

PMID- 20150519
TI  - Ion fluxes across the pitcher walls of three Bornean Nepenthes pitcher plant
      species: flux rates and gland distribution patterns reflect nitrogen
      sequestration strategies.
AB  - Nepenthes pitcher plant species differ in their prey capture strategies, prey
      capture rates, and pitcher longevity. In this study, it is investigated whether
      or not interspecific differences in nutrient sequestration strategy are reflected
      in the physiology and microstructure of the pitchers themselves. Using a non
      invasive technique (MIFE), ion fluxes in pitchers of Nepenthes ampullaria Jack,
      Nepenthes bicalcarata Hook.f., and Nepenthes rafflesiana Jack were measured.
      Scanning electron microscopy was also used to characterize the distribution of
      glandular and other structures on the inner pitcher walls. The results
      demonstrate that nutrient sequestration strategy is indeed mirrored in pitcher
      physiology and microstructure. Species producing long-lived pitchers with low
      prey capture rates (N. ampullaria, N. bicalcarata) showed lower rates of NH(4)(+)
      uptake than N. rafflesiana, a species producing short-lived pitchers with high
      capture rates. Crucially, species dependent upon aquatic commensals (N.
      ampullaria, N. bicalcarata) actively manipulated H(+) fluxes to maintain less
      acid pitcher fluid than found in 'typical' species; in addition, these species
      lacked the lunate cells and epicuticular waxes characteristic of 'typical'
      insectivorous congeners. An unexpected finding was that ion fluxes occurred in
      the wax-covered, non-glandular zones in N. rafflesiana. The only candidates for
      active transport of aqueous ions in these zones appear to be the epidermal cells
      lying beneath the lunate cells, as these are the only sites not visibly coated
      with epicuticular waxes.

PMID- 20150520
TI  - Influence of body weight and gender on the pharmacokinetics, pharmacodynamics,
      and antihypertensive efficacy of aliskiren.
AB  - Gender and body weight influence the pharmacokinetics and pharmacodynamics of
      many drugs. This pooled analysis of 17 clinical studies evaluated the effect of
      gender, body mass index (BMI), body weight, and lean body weight (LBW) on the
      pharmacokinetics of the direct renin inhibitor aliskiren in healthy volunteers (n
      = 392). A separate pooled analysis of 5 clinical studies in patients with
      hypertension (n = 2327) assessed the influence of gender and BMI on the effects
      of aliskiren on plasma renin activity and blood pressure. Area under the
      aliskiren plasma concentration-time curve (AUC(tau)) was 22% lower and the peak
      aliskiren plasma concentration (C(max)) was 24% lower in men than women (P <
      .05). BMI was not significantly correlated with AUC(tau) (r = 0.005; P = .917);
      AUC(tau) was negatively correlated with body weight (r = -0.235; P < .0001) and
      LBW (r = -0.295; P < .0001). Results were similar for C(max). Adjusting
      individual aliskiren AUC(tau) and C(max) values for overall mean body weight or
      LBW abolished gender differences. Based on r(2) values, LBW variation accounted
      for 8.9% of aliskiren AUC(tau) variation. In patients with hypertension, gender
      and BMI did not significantly influence the effects of aliskiren on plasma renin
      activity or blood pressure. It was concluded that lower systemic exposure to
      aliskiren in men versus women relates to differences in body weight; neither
      gender nor body weight has clinically relevant effects on the pharmacokinetics or
      pharmacodynamics of aliskiren.

PMID- 20150521
TI  - Evaluation of the single- and multiple-dose pharmacokinetics of fentanyl buccal
      soluble film in normal healthy volunteers.
AB  - Fentanyl buccal soluble film (FBSF) is a rapidly absorbed transmucosal
      formulation of fentanyl for the management of breakthrough pain in opioid
      tolerant patients with cancer. This open-label, 3-period, sequential dose study
      evaluated the dose-to-dose reproducibility of the pharmacokinetics of fentanyl
      following the administration of 600- or 1800-microg doses of FBSF in 12
      naltrexone-blocked, healthy adult volunteers. Subjects received 3 study
      treatments: single doses of 600 microg of FBSF on day 1 and day 4 and three 600
      microg doses administered at 1-hour intervals on day 7. Plasma fentanyl
      concentrations were measured over a 48-hour period after each single dose of FBSF
      and 72 hours after the 3-dose regimen. Peak plasma concentrations (mean C(max) =
      1.08 and 1.01 ng/mL) and overall exposure (mean AUC(0-12) = 6.3 and 6.2 h.ng/mL;
      mean AUC(inf) = 9.14 and 9.60 h.ng/mL) were nearly identical after the 2 single
      doses (P >or= .1, all comparisons). C(max) and overall fentanyl exposure
      (AUC(inf)) increased approximately 3-fold with the 3-dose regimen compared with
      the single-dose periods. Fentanyl plasma concentrations following single doses of
      FBSF were reproducible, and 3 doses administered 1 hour apart produced a tripling
      in exposure and maximal concentration compared with a single dose.

PMID- 20150522
TI  - Effect of a high-fat meal on the pharmacokinetics of saxagliptin in healthy
      subjects.

PMID- 20150523
TI  - Effect of a single gemfibrozil dose on the pharmacokinetics of rosuvastatin in
      bile and plasma in healthy volunteers.
AB  - The effect of a single intrajejunal dose of gemfibrozil (600 mg) on the plasma
      pharmacokinetics and biliary excretion of a single intrajejunal dose of
      rosuvastatin (20 mg) was investigated by using a multichannel catheter positioned
      in the distal duodenum-proximal jejunum in 8 healthy volunteers. Bile and plasma
      samples were collected every 20 minutes for 200 minutes, with additional plasma
      samples being drawn for up to 48 hours. Gemfibrozil did not affect the
      bioavailability of rosuvastatin, although it increased the apparent absorption
      phase during the initial 200 minutes (AUC(plasma,200min)) by 1.56-fold (95%
      confidence interval, 1.14-2.15). The interaction was less pronounced in this
      single-dose study than in a previous report when gemfibrozil was administered
      repeatedly; nevertheless, the interaction coincided with the highest exposure to
      gemfibrozil. The plausible reason why the interaction in this investigation was
      only minor is the low exposure to gemfibrozil (and its metabolites), suggesting
      that the total plasma concentration of gemfibrozil needs to be above 20 uM to
      affect the disposition of rosuvastatin. This study demonstrates the value of
      monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug
      under investigation, to improve the mechanistic interpretation.

PMID- 20150524
TI  - Population pharmacokinetics and pharmacodynamics of inhaled ciclesonide and
      fluticasone propionate in patients with persistent asthma.
AB  - Inhaled corticosteroids, such as fluticasone propionate (FP) and ciclesonide
      (CIC), are commonly used for the treatment of asthma. The objectives of this
      study were to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of FP
      and a pharmacologically active metabolite of CIC (desisobutyryl-ciclesonide [Des
      CIC]) using a nonlinear mixed-effects modeling approach, to investigate selected
      covariate effects on PK and PD parameters of FP and Des-CIC, and to assess the
      systemic effects of FP and CIC on serum cortisol suppression in patients with
      persistent asthma. This was a randomized, double-blind, placebo-controlled,
      double-dummy, 5-period, crossover, multicenter clinical study. A total of 32
      patients were enrolled and given basic asthma medication (salmeterol 50 ug twice
      per day [BID] and CIC 160 ug daily in the evening) through the entire study.
      During crossover periods, patients were given placebo or CIC 160 ug BID (ex
      actuator), CIC 320 ug BID (ex actuator), FP 220 ug BID (ex actuator), or FP 440
      ug BID (ex actuator). The FP and Des-CIC PK were described using a 1-compartment
      and a 2-compartment linear model with first-order absorption process. The FP
      population PK parameter estimates of the first-order rate constant, relative
      clearance, and volume of distribution were 4.07 1/h, 890 L/h, and 9800 L,
      respectively. The Des-CIC PK parameter estimates of the first-order absorption
      rate constant were 2.63 1/h, clearance 202 L/h (non-CIC treatment) or 271 L/h
      (CIC treatment), and volume of distribution 947 L. Gender was a significant
      covariate on the maximum cortisol release rate (male, 3440 ug/h; female, 4310
      ug/h). The CIC showed the least serum cortisol suppression of the tested dosing
      regimens.

PMID- 20150525
TI  - Potential use of erythromycin to prevent and treat prosthetic failure.
AB  - Prolonged prosthetic life span is a goal that orthopedic surgeons are pursuing.
      Both septic and aseptic loosening may lead to prosthetic failure. For decades,
      antibiotics have been applied in arthroplasty to prevent septic loosening, with
      excellent clinical results, although few therapies have been able to prevent
      aseptic loosening. Research on aseptic loosening indicates that osteoclasts play
      an essential role in this process. Thus, the exploration of osteoclastogenesis
      inhibitor has become of interest. Erythromycin is a broad-spectrum antimicrobial
      that has been used to prevent postoperative infection after artificial joint
      replacement. A new function to inhibit particle-induced osteolysis has been
      discovered recently. Fundamental research indicates that erythromycin
      administration should be an excellent method for the prophylaxis of prosthetic
      failure and should increase the life span of artificial joint in clinics.

PMID- 20150526
TI  - Effects of concomitant therapy with diltiazem on the lipid responses to
      simvastatin in Chinese subjects.
AB  - Diltiazem increases systemic exposure to simvastatin via inhibition of CYP3A.
      This study assessed the impact of this interaction on the lipid-lowering effects
      of simvastatin. Chinese patients with hypercholesterolemia were randomized to
      receive simvastatin 20 mg daily alone or together with diltiazem 60 mg 3 times
      daily for 4 weeks with a washout period of 4 weeks in an open-label, crossover
      study. Blood pressure, fasting serum lipid profile, and safety tests were
      determined at baseline and after each treatment period. Trough serum diltiazem
      was measured at the end of the 4-week combination treatment. In the 30 patients
      who completed the study, simvastatin treatment significantly reduced low-density
      lipoprotein cholesterol by mean (+/- standard error) 41.0% +/- 2.2% (P < .001),
      and the combination with diltiazem showed an additional reduction of 1.66% (95%
      confidence interval: -4.63 to 7.96, P > .05). The additional change in low
      density lipoprotein cholesterol with diltiazem showed a nonsignificant positive
      correlation with the trough serum diltiazem concentration (R(2) = 0.142, P =
      .058). Co-administration of diltiazem 60 mg 3 times daily with simvastatin 20 mg
      daily tended to increase the changes in lipid parameters in these Chinese
      subjects, but the effects did not reach significance.

PMID- 20150527
TI  - Understanding the relative roles of pharmacogenetics and ontogeny in pediatric
      drug development and regulatory science.
AB  - Understanding the dose-exposure-response relationship across the pediatric age
      spectrum from preterm and term newborns to infants, children, adolescents, and
      adults is a major challenge for clinicians, pharmaceutical companies, and
      regulatory agencies. Over the past 3 decades, clinical investigations of many
      drugs commonly used in pediatric therapeutics have provided valuable insights
      into age-associated differences in drug disposition and action. However, our
      understanding of the contribution of genetic variation to variability in drug
      disposition and response in children generally has lagged behind that of adults.
      This article proposes a systematic approach that can be used to assess the
      relative contributions of ontogeny and genetic variation for a given compound.
      Application of the strategy is illustrated using the current regulatory dilemma
      posed by the safety and effectiveness of over-the-counter cough and cold remedies
      as an example. The results of the analysis can be used to aid in the design of
      studies to yield maximally informative data in pediatric populations of different
      ages and developmental stages and thereby improve the efficiency of study design.

PMID- 20150528
TI  - Remembrance of dead cells past: discovering that the extracellular matrix is a
      cell survival factor.
AB  - In 1992, Jere Meredith and I followed up on a serendipitous observation and
      showed that matrix deprivation can lead to apoptosis. Our article in Molecular
      Biology of the Cell, together with work form Steve Frisch's lab, helped establish
      the paradigm that integrin signals control cell survival in a variety of systems.
      It has been a pleasure to watch that work take on a life of its own as other
      investigators have explored its role in processes such as cavitation, regression
      of the mammary gland at the end of pregnancy, cancer metastasis, and tumor
      resistance to chemotherapy. Recently, we described an exception to the paradigm:
      In some tumors, reagents that activate integrin signaling enhance apoptosis in
      response to chemotherapy.

PMID- 20150529
TI  - Associations of lipoprotein lipase gene polymorphisms with longitudinal plasma
      lipid trends in young adults: The Coronary Artery Risk Development in Young
      Adults (CARDIA) study.
AB  - BACKGROUND: Genome-wide association studies in European Americans have reported
      several single-nucleotide polymorphisms (SNPs) in the lipoprotein lipase gene
      associated with plasma levels of high-density lipoprotein cholesterol (HDL-C) and
      triglycerides. However, the influences of the lipoprotein lipase SNPs on
      longitudinal changes of these lipids have not been systematically examined.
      METHODS AND RESULTS: On the basis of data from 2045 African Americans and 2116
      European Americans in the Coronary Artery Risk Development in Young Adults study,
      we investigated cross-sectional and longitudinal associations of lipids with 8
      lipoprotein lipase SNPs, including the 2 that have been reported in genome-wide
      association studies. Plasma levels of HDL-C and triglycerides were measured at 7
      examinations during 20 years of follow-up. In European Americans, rs328
      (Ser447Stop), rs326, and rs13702 were significantly associated with cross
      sectional interindividual variations in triglycerides and HDL-C (P<0.005) and
      with their longitudinal changes over time (P<0.05). The minor alleles in rs326,
      rs328, and rs13702 that predispose an individual to lower triglycerides and
      higher HDL-C levels at young adulthood further slow down the trajectory increase
      in triglycerides and decrease in HDL-C during 20 years of follow-up. In African
      Americans, these 3 SNPs were significantly associated with triglycerides, but
      only rs326 and rs13702 were associated with HDL-C (P<0.008). Rs328 showed a
      stronger association in European Americans than in African Americans, and
      adjustment for it did not remove all of the associations for the other SNPs.
      Longitudinal changes in either trait did not differ significantly by SNP
      genotypes in African Americans. CONCLUSIONS: Our data suggest that aging
      interacts with LPL gene variants to influence the longitudinal lipid variations,
      and there is population-related heterogeneity in the longitudinal associations.

PMID- 20150530
TI  - An evaluation of 'Reach Out Central': an online gaming program for supporting the
      mental health of young people.
AB  - The objective of this study was to conduct an evaluation of Reach Out Central
      (ROC), an online gaming program designed to support the mental health of people
      aged 16-25. The evaluation sought to determine the benefit of playing ROC on
      alcohol use, use of coping strategies, psychological distress, resilience and
      satisfaction with life. Changes in mental health literacy, mental health stigma
      and willingness to seek help and program satisfaction were also investigated. A
      single group (N = 266) quasi-experimental repeated measures (pre-, post-program,
      2-month follow-up) design was employed. The results demonstrated positive
      improvements across all outcome measures for females; however, a non-significant
      worsening effect was observed for males on seeking support, avoidance and
      resilience. Improvements for both genders were observed on mental health literacy
      and help-seeking. However, literacy levels and help-seeking were significantly
      higher, and stigma significantly lower for females. Program satisfaction ratings
      were high irrespective of gender. Although some inconsistencies between genders
      were noted, ROC appears to enhance protective factors for the prevention or early
      intervention of mental health disorders. The results of this study need to be
      viewed with its limitations in mind, specifically, the use of an open trial
      methodology and the small number of male participants.

PMID- 20150531
TI  - Factors associated with high use of a workplace web-based stress management
      program in a randomized controlled intervention study.
AB  - In web-based health promotion programs, large variations in participant
      engagement are common. The aim was to investigate determinants of high use of a
      worksite self-help web-based program for stress management. Two versions of the
      program were offered to randomly selected departments in IT and media companies.
      A static version of the program including health screening tool, diary and
      information about stress was offered to the control group. Additional materials,
      i.e. interactive, cognitive-based and classical stress management exercises and a
      chat room, were offered to the intervention group. Baseline data regarding
      participants' demographics, health (self-ratings and biological measures),
      lifestyle, work-related factors and group membership were analyzed to study
      determinants of employees' participation in the program during a period of 12
      months. Multiple logistic regression analysis was used and found intervention
      group membership, being a woman, having at most a secondary education, regular
      physical exercise habits and having positive expectations of the program were
      significant predictors of high use. The findings demonstrate that the
      interactivity of a web-based program is an important factor for determining
      participation in a web-based worksite stress management program. Implications for
      those developing and implementing future web-based health promotion activities
      are discussed.

PMID- 20150532
TI  - Autoimmunity in membranous nephropathy targets aldose reductase and SOD2.
AB  - Glomerular targets of autoimmunity in human membranous nephropathy are poorly
      understood. Here, we used a combined proteomic approach to identify specific
      antibodies against podocyte proteins in both serum and glomeruli of patients with
      membranous nephropathy (MN). We detected specific anti-aldose reductase (AR) and
      anti-manganese superoxide dismutase (SOD2) IgG(4) in sera of patients with MN. We
      also eluted high titers of anti-AR and anti-SOD2 IgG(4) from microdissected
      glomeruli of three biopsies of MN kidneys but not from biopsies of other
      glomerulonephritides characterized by IgG deposition (five lupus nephritis and
      two membranoproliferative glomerulonephritis). We identified both antigens in MN
      biopsies but not in other renal pathologies or normal kidney. Confocal and
      immunoelectron microscopy (IEM) showed co-localization of anti-AR and anti-SOD2
      with IgG(4) and C5b-9 in electron-dense podocyte immune deposits. Preliminary in
      vitro experiments showed an increase of SOD2 expression on podocyte plasma
      membrane after treatment with hydrogen peroxide. In conclusion, our data support
      AR and SOD2 as renal antigens of human MN and suggest that oxidative stress may
      drive glomerular SOD2 expression.

PMID- 20150533
TI  - A GREM1 gene variant associates with diabetic nephropathy.
AB  - Gremlin, a cell growth and differentiation factor, promotes the development of
      diabetic nephropathy in animal models, but whether GREM1 gene variants associate
      with diabetic nephropathy is unknown. We comprehensively screened the 5' upstream
      region (including the predicted promoter), all exons, intron-exon boundaries,
      complete untranslated regions, and the 3' region downstream of the GREM1 gene. We
      identified 31 unique variants, including 24 with a minor allele frequency
      exceeding 5%, and 9 haplotype-tagging single nucleotide polymorphisms (htSNPs).
      We selected one additional variant that we predicted to alter transcription
      factor binding. We genotyped 709 individuals with type 1 diabetes of whom 267 had
      nephropathy (cases) and 442 had no evidence of kidney disease (controls). Three
      individual SNPs significantly associated with nephropathy at the 5% level, and
      two remained significant after adjustment for multiple testing. Subsequently, we
      genotyped a replicate population comprising 597 cases and 502 controls: this
      population supported an association with one of the SNPs (rs1129456; P = 0.0003).
      Combined analysis, adjusted for recruitment center (n = 8), suggested that the T
      allele conferred greater odds of nephropathy (OR 1.69; 95% CI 1.36 to 2.11). In
      summary, the GREM1 variant rs1129456 associates with diabetic nephropathy,
      perhaps explaining some of the genetic susceptibility to this condition.

PMID- 20150534
TI  - NFkappaB promotes inflammation, coagulation, and fibrosis in the aging
      glomerulus.
AB  - The peak prevalence of ESRD from glomerulosclerosis occurs at 70 to 79 years. To
      understand why old glomeruli are prone to failure, we analyzed the Fischer 344
      rat model of aging under ad libitum-fed (rapid aging) and calorie-restricted
      (slowed aging) conditions. All glomerular cells contained genes whose expression
      changed "linearly" during adult life from 2 to 24 months: mesangial cells (e.g.,
      MMP9), endothelial cells (e.g., ICAM and VCAM), parietal epithelial cells (e.g.,
      ceruloplasmin), and podocytes (e.g., nephrin and prepronociceptin). Patterns of
      aging glomerular gene expression closely resembled atherosclerosis, including
      activation of endothelial cells, epithelial cells, and macrophages, as well as
      proinflammatory pathways related to cell adhesion, chemotaxis, blood coagulation,
      oxidoreductases, matrix metalloproteinases, and TGF-beta activation. We used a
      nonbiased data-mining approach to identify NFkappaB as the likely transcriptional
      regulator of these events. We confirmed NFkappaB activation by two independent
      methods: translocation of NFkappaB p50 to glomerular nuclei and ChIP assays
      demonstrating NFkappaB p50 binding to the kappaB motif of target genes in old
      versus young glomeruli. These data suggest that old glomeruli exhibit NFkappaB
      associated up-regulation of a proinflammatory, procoagulable, and profibrotic
      phenotype compared with young glomeruli; these distinctions could explain their
      enhanced susceptibility to failure. Furthermore, these results provide a
      potential mechanistic explanation for the close relationship between ESRD and
      atherosclerotic organ failure as two parallel arms of age-associated NFkappaB
      driven processes.

PMID- 20150535
TI  - Maintenance of glomerular filtration barrier integrity requires laminin alpha5.
AB  - Mutation of the mouse laminin alpha5 gene results in a variety of developmental
      defects, including defects in kidney structure and function. Whereas the total
      absence of laminin alpha5 results in breakdown of the glomerular basement
      membrane (GBM) and failed glomerular vascularization, a hypomorphic Lama5
      mutation (the Lama5(neo) allele) results in proteinuria, hematuria, polycystic
      kidney disease (PKD), and death 3 to 4 weeks after birth. Here, we examined the
      role of podocyte-derived laminin alpha5 via podocyte-specific inactivation of
      Lama5 and podocyte-specific rescue of the Lama5(neo) mutation. Podocyte-specific
      inactivation of Lama5 resulted in varying degrees of proteinuria and rates of
      progression to nephrotic syndrome. The GBM of proteinuric mice appeared thickened
      and "moth-eaten," and podocyte foot processes became effaced. Podocyte-specific
      restoration of laminin alpha5 production using two distinct strategies in
      Lama5(neo/neo) mice resulted in the resolution of proteinuria, hematuria, and
      PKD. These results suggest that the development of normal GBM structure and
      function requires podocyte-derived laminin alpha5 during and after
      glomerulogenesis and present a unique mechanism for the pathogenesis of PKD in
      these mice.

PMID- 20150536
TI  - Phenotype and genotype characterization of adenine phosphoribosyltransferase
      deficiency.
AB  - Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive
      disorder causing 2,8-dihydroxyadenine stones and renal failure secondary to
      intratubular crystalline precipitation. Little is known regarding the clinical
      presentation of APRT deficiency, especially in the white population. We
      retrospectively reviewed all 53 cases of APRT deficiency (from 43 families)
      identified at a single institution between 1978 and 2009. The median age at
      diagnosis was 36.3 years (range 0.5 to 78.0 years). In many patients, a several
      year delay separated the onset of symptoms and diagnosis. Of the 40 patients from
      33 families with full clinical data available, 14 (35%) had decreased renal
      function at diagnosis. Diagnosis occurred in six (15%) patients after reaching
      ESRD, with five diagnoses made at the time of disease recurrence in a renal
      allograft. Eight (20%) patients reached ESRD during a median follow-up of 74
      months. Thirty-one families underwent APRT sequencing, which identified 54 (87%)
      mutant alleles on the 62 chromosomes analyzed. We identified 18 distinct
      mutations. A single T insertion in a splice donor site in intron 4 (IVS4 +
      2insT), which produces a truncated protein, accounted for 40.3% of the mutations.
      We detected the IVS4 + 2insT mutation in two (0.98%) of 204 chromosomes of
      healthy newborns. This report, which is the largest published series of APRT
      deficiency to date, highlights the underdiagnosis and potential severity of this
      disease. Early diagnosis is crucial for initiation of effective treatment with
      allopurinol and for prevention of renal complications.

PMID- 20150537
TI  - The clinical importance of nephron mass.
AB  - Abundant evidence supports the association between low birth weight (LBW) and
      renal dysfunction in humans. Anatomic measurements of infants, children, and
      adults show significant inverse correlation between LBW and nephron number.
      Nephron numbers are also lower in individuals with hypertension compared with
      normotension among white and Australian Aboriginal populations. The relationship
      between nephron number and hypertension among black individuals is still unclear,
      although the high incidence of LBW predicts low nephron number in this population
      as well. LBW, a surrogate for low nephron number, also associates with increasing
      BP from childhood to adulthood and increasing risk for chronic kidney disease in
      later life. Because nephron numbers can be counted only postmortem, surrogate
      markers such as birth weight, prematurity, adult height, reduced renal size, and
      glomerulomegaly are potentially useful for risk stratification, for example,
      during living-donor assessment. Because early postnatal growth also affects
      subsequent risk for higher BP or reduced renal function, postnatal nutrition, a
      potentially modifiable factor, in addition to intrauterine effects, has
      significant influence on long-term cardiovascular and renal health.

PMID- 20150538
TI  - Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the
      roles of fetuin-A, adiponectin, and AMPK.
AB  - Obesity is a risk factor for chronic kidney disease (CKD) and nonalcoholic fatty
      liver disease (NAFLD). Recent studies identify mechanisms common to both diseases
      linked through an interorgan communication orchestrated by fetuin-A and
      adiponectin. In liver and kidney, the energy sensor 5'-AMP activated protein
      kinase (AMPK) is pivotal to directing podocytes and hepatocytes to compensatory
      and potentially deleterious pathways, leading to inflammatory and profibrotic
      cascades culminating in end-organ damage. Regulation of these early upstream
      pathways may provide new therapeutic targets for these increasingly common
      sequelae of obesity.

PMID- 20150539
TI  - Integrative urinary peptidomics in renal transplantation identifies biomarkers
      for acute rejection.
AB  - Noninvasive methods to diagnose rejection of renal allografts are unavailable.
      Mass spectrometry followed by multiple-reaction monitoring provides a unique
      approach to identify disease-specific urine peptide biomarkers. Here, we
      performed urine peptidomic analysis of 70 unique samples from 50 renal transplant
      patients and 20 controls (n = 20), identifying a specific panel of 40 peptides
      for acute rejection (AR). Peptide sequencing revealed suggestive mechanisms of
      graft injury with roles for proteolytic degradation of uromodulin (UMOD) and
      several collagens, including COL1A2 and COL3A1. The 40-peptide panel
      discriminated AR in training (n = 46) and test (n = 24) sets (area under ROC
      curve >0.96). Integrative analysis of transcriptional signals from paired renal
      transplant biopsies, matched with the urine samples, revealed coordinated
      transcriptional changes for the corresponding genes in addition to dysregulation
      of extracellular matrix proteins in AR (MMP-7, SERPING1, and TIMP1). Quantitative
      PCR on an independent set of 34 transplant biopsies with and without AR validated
      coordinated changes in expression for the corresponding genes in rejection
      tissue. A six-gene biomarker panel (COL1A2, COL3A1, UMOD, MMP-7, SERPING1, TIMP1)
      classified AR with high specificity and sensitivity (area under ROC curve =
      0.98). These data suggest that changes in collagen remodeling characterize AR and
      that detection of the corresponding proteolytic degradation products in urine
      provides a noninvasive diagnostic approach.

PMID- 20150540
TI  - Normal ciliogenesis requires synergy between the cystic kidney disease genes MKS
      3 and NPHP-4.
AB  - Cilia dysfunction contributes to renal cyst formation in multiple human syndromes
      including nephronophthisis (NPHP), Meckel-Gruber syndrome (MKS), Joubert syndrome
      (JBTS), and Bardet-Beidl syndrome (BBS). Although genetically heterogeneous,
      these diseases share several loci that affect cilia and/or basal body proteins,
      but the functions and interactions of these gene products are incompletely
      understood. Here, we report that the ciliated sensory neurons (CSNs) of C.
      elegans express the putative transmembrane protein MKS-3, which localized to the
      distal end of their dendrites and to the cilium base but not to the cilium
      itself. Localization of MKS-3 and other known MKS and NPHP proteins partially
      overlapped. By analyzing mks-3 mutants, we found that ciliogenesis did not
      require MKS-3; instead, cilia elongated and cilia-mediated chemoreception was
      abnormal. Genetic analysis indicated that mks-3 functions in a pathway with other
      mks genes. Furthermore, mks-1 and mks-3 genetically interacted with a separate
      pathway (involving nphp-1 and nphp-4) to influence proper positioning,
      orientation, and formation of cilia. Combined disruption of nphp and mks pathways
      had cell nonautonomous effects on C. elegans sensilla. Taken together, these data
      demonstrate the importance of mutational load on the presentation and severity of
      ciliopathies and expand the understanding of the interactions between ciliopathy
      genes.

PMID- 20150541
TI  - Age-related macular degeneration: why should stroke physicians care?

PMID- 20150542
TI  - Embolus trajectory through a physical replica of the major cerebral arteries.
AB  - BACKGROUND AND PURPOSE: The observed distribution of cerebral infarcts varies
      markedly from expectations based on blood-flow volume or Doppler embolus
      detection. In this study, we used an in vitro model of the cerebral arteries to
      test whether embolus microspheres encountering the circle of Willis are carried
      proportionally to volume flow or express a preferred trajectory related to
      arterial morphology or embolus size. METHODS: Our model consisted of a patient
      specific silicone replica of the cerebral macrocirculation featuring
      physiologically realistic pulsatile flow of a blood-mimicking fluid at
      approximately 1000 mL/min and an input pressure of approximately 150/70 mm Hg.
      Particles of 200, 500, and 1000 microm diameter with equivalent density to
      thrombus were introduced to the carotid arteries and counted on exiting the model
      outlets. RESULTS: The middle cerebral arteries (MCAs) of the replica attracted a
      disproportionate number of emboli compared with the anterior cerebral arteries;
      98%+/-3% of 1000 microm and 93%+/-2% of 500 microm emboli entered the MCA
      compared with 82%+/-5% of the flow. The observed distribution of large emboli was
      consistent with the ratio of MCA:anterior cerebral artery infarcts, approximately
      95% of which occur in territories supplied by the MCA. With decreasing embolus
      size, the distribution of emboli approaches that of the flow (approximately 89%
      of 200 microm emboli took the MCA). CONCLUSIONS: Embolus trajectory through the
      cerebral arteries is dependent on embolus size and strongly favors the MCA for
      large emboli. The 70:30 ratio of MCA:anterior cerebral artery emboli observed by
      Doppler ultrasound is consistent with the trajectories of small emboli that tend
      to be asymptomatic.

PMID- 20150543
TI  - Quality-adjusted life expectancy (QALE) and loss of QALE for patients with
      ischemic stroke and intracerebral hemorrhage: a 13-year follow-up.
AB  - BACKGROUND AND PURPOSE: Few studies have evaluated the long-term health impact of
      stroke as categorized into different subtypes. The aim of this study is to
      quantify the loss of quality-adjusted life expectancy related to ischemic stroke
      and intracerebral hemorrhage. METHODS: The hospital-based cohort, which consisted
      of 13,194 patients with first-ever stroke onset dates between 1995 and 2007, was
      classified into lacunar and nonlacunar infarctions and intracerebral hemorrhages.
      After linking with the National Mortality Registry, survival functions were
      determined and extrapolated over a 50-year period based on the survival ratio
      between the patients' survival and age- and sex-matched reference population's as
      calculated from the vital statistics of Taiwan. The survival functions were then
      multiplied by the quality of life assessed under the EuroQol 5-dimension (EQ-5D)
      questionnaire based on a sample of 486 patients with stroke. RESULTS: The quality
      adjusted life expectancy for a patient with ischemic stroke was 8.7 quality
      adjusted life-years with an average loss of 8.3 quality-adjusted life-years, and
      there appeared to be no difference between lacunar and nonlacunar infarctions.
      Patients with intracerebral hemorrhage had a similar quality-adjusted life
      expectancy as those with ischemic stroke but with a significantly greater loss
      relative to the reference population (14.1 quality-adjusted life-years) because
      of younger ages. CONCLUSION: The lifelong health burden due to stroke was
      approximately 9.5 quality-adjusted life-years and should be considered in future
      cost-effectiveness analyses for prevention.

PMID- 20150544
TI  - Cystatin C and the risk for cardiovascular events in patients with asymptomatic
      carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Renal dysfunction is a risk factor for cardiovascular
      events in patients with atherosclerosis. Unlike serum creatinine or estimated
      glomerular filtration rate, cystatin C reflects renal dysfunction independent of
      factors such as sex, weight, and race. We investigated whether baseline serum
      levels of cystatin C predict major cardiovascular events in patients with
      asymptomatic carotid atherosclerosis and compared the predictive value of
      cystatin C to these established markers of renal function. METHODS: We
      prospectively studied 1004 of 1286 consecutive patients with carotid ultrasound
      scanning. Patients were followed for the occurrence of major cardiovascular
      events, a composite of myocardial infarction, percutaneous coronary intervention,
      coronary bypass graft, stroke, and death. RESULTS: During a median of 3 years of
      follow-up, we recorded 346 major cardiovascular events in 311 patients. The risk
      for a first major cardiovascular event increased significantly with increasing
      quintiles of cystatin C; hazard ratios ranged from 1.18 to 1.94 for the highest
      versus the lowest quintile (P<0.001 for trend). Creatinine levels showed no
      significant association with major cardiovascular events, and for glomerular
      filtration rate, only the lowest quintile was moderately associated with adverse
      cardiovascular outcome. CONCLUSIONS: Cystatin C was significantly and gradually
      associated with future cardiovascular events in patients with carotid
      atherosclerosis. In contrast, neither serum creatinine nor estimated glomerular
      filtration rate were significant predictors of adverse cardiovascular outcomes.

PMID- 20150545
TI  - Ischemic stroke in cancer patients with and without conventional mechanisms: a
      multicenter study in Korea.
AB  - BACKGROUND AND METHODS: To assess the precise mechanisms of stroke in cancer
      patients, we analyzed the data for cancer patients with acute ischemic stroke
      registered from 6 centers in South Korea. Clinical features, risk factors,
      diffusion-weighted imaging lesion patterns, and laboratory findings including D
      dimer levels were compared between patients with conventional stroke mechanisms
      (CSMs) and cryptogenic group. RESULTS: A total of 161 patients were included in
      this study: 97 (60.2%) patients in the CSM group and 64 (39.8%) in the
      cryptogenic group. Patients in the CSM group were older and vascular risk factors
      were more prevalent than in the cryptogenic group. Diffusion-weighted imaging
      patterns of multiple lesions involving multiple arterial territories were
      observed more frequently in the cryptogenic group than in the CSM group. In
      addition, levels of the D-dimer were higher in the cryptogenic group than in the
      CSM group (11.5+/-14.6 versus 3.6+/-10.3 microg/dL). In multivariate analysis,
      the diffusion-weighted imaging lesion pattern of multiple vascular territories
      (odds ratio, 11.2; 95% CI, 3.74 to 33.3), and D-dimer levels of >1.11 microg/dL
      (odds ratio, 10.6; 95% CI, 3.29 to 33.8) were associated independently with the
      cryptogenic group. CONCLUSIONS: Stroke outside of CSM occurred in a large number
      in cancer patients. In stroke patients with cancer, d-dimer levels and diffusion
      weighted imaging lesion patterns may be helpful in early identification of non
      CSMs (especially coagulopathy associated with cancer) and possibly in guiding
      preventive strategies for stroke.

PMID- 20150546
TI  - Neovascular age-related macular degeneration and the risk of stroke: a 5-year
      population-based follow-up study.
AB  - BACKGROUND AND PURPOSE: Using a nationwide population-based data set from Taiwan,
      this study investigated the relationship between neovascular age-related macular
      degeneration (AMD) and the risk of stroke over a 5-year period. METHOD: The study
      cohort comprised 209 patients who received treatment for AMD between 1999 and
      2001. We randomly selected 1045 subjects matched with the study cohort in terms
      of age and gender for comparison. Cox proportional hazard regressions were
      performed to compare the 5-year stroke-free survival rate. RESULTS: Among the
      sampled patients, 142 patients (11.3%) had strokes during the 5-year follow-up
      period, 38 (18.2% of the patients with AMD) from the study cohort and 104 (9.9%
      of patients in the comparison cohort) from the comparison cohort. After adjusting
      for the patient's age, gender, monthly income, level of urbanization, and the
      geographic region of the community in which the patient resided and
      comorbidities, the hazard ratio for stroke during the follow-up period was 2.01
      (P=0.001) times greater for patients with AMD than for patients without AMD. The
      adjusted hazard ratio for stroke during the follow-up period was 2.21 (P=0.001)
      times higher for patients with AMD > or = 65 years old compared with the same age
      group in the comparison cohort. However, no significant difference was observed
      in the risk of stroke between patients with AMD <65 years of age and comparison
      patients in the same age group. CONCLUSION: We conclude that neovascular AMD is
      associated with a higher risk of stroke for patients with AMD > or = 65 years
      old.

PMID- 20150547
TI  - Reliability of measuring lesion volumes in transient ischemic attack and minor
      stroke.
AB  - BACKGROUND AND PURPOSE: Lesion volume measurements in disabling ischemic stroke
      have excellent reliability, but it is not clear whether this is also true for
      small lesions. We assessed the reliability of measuring baseline and follow-up
      lesion volumes in transient ischemic attack and minor stroke. METHODS: Patients
      who presented with a transient ischemic attack or minor stroke (NIHSS < or = 3)
      who had brain MRI within 24 hours from symptom onset and at 30-day follow-up and
      had an acute lesion on baseline MRI were included. Using semiautomated software,
      4 stroke fellows independently assessed ischemic lesions twice on acute diffusion
      weighted imaging and follow-up fluid-attenuated inversion recovery. RESULTS:
      Eighty patients were included, with a median baseline NIHSS of 1. Mean baseline
      diffusion-weighted imaging lesion volume was 3.4+/-7.4 mL (87.5% had <5 mL).
      There was excellent inter-rater/intrarater reliability, with intraclass
      correlation coefficients of 0.94/0.96 for acute diffusion-weighted imaging,
      0.74/0.92 for follow-up fluid-attenuated inversion recovery, and 0.81/0.93 for
      growth. CONCLUSIONS: We found excellent concordance between and within raters for
      acute diffusion-weighted imaging and 30-day follow-up fluid-attenuated inversion
      recovery lesion volume measurements in patients with transient ischemic attack
      and minor stroke.

PMID- 20150548
TI  - Critical role for copper/zinc-superoxide dismutase in preventing spontaneous
      intracerebral hemorrhage during acute and chronic hypertension in mice.
AB  - BACKGROUNDS AND PURPOSE: Superoxide is associated with spontaneous intracerebral
      hemorrhage (ICH) during hypertension. The goal of this study was to test the
      hypothesis that changes in superoxide, in genetically altered mice with deletion
      and overexpression of copper/zinc-superoxide dismutase (SOD1), modulate
      susceptibility to ICH. METHODS: Chronic hypertension was produced by infusion of
      angiotensin II and an inhibitor of nitric oxide synthase in drinking water in
      SOD1 transgenic (SOD1Tg) mice, SOD1-deficient (SOD1(-/-)) mice, and their
      respective wild-type littermates. Acute hypertension was produced by daily
      injections of angiotensin II in some mice with chronic hypertension to produce
      ICH. We evaluated susceptibility to ICH, oxidative stress (superoxide, NAD[P]H
      oxidase activity, SOD activity), gene expression, and activity of matrix
      metalloproteinases. RESULTS: Incidence, size, and number of ICHs were reduced in
      SOD1Tg mice and were increased in SOD1(-/-) mice compared with their wild-type
      littermates. Levels of superoxide increased in the brain even before developing
      ICH in wild-type littermates, whereas levels of superoxide remained low in SOD1Tg
      mice. Changes in level of matrix metalloproteinase-9 paralleled oxidative stress
      in SOD1Tg mice and wild-type littermates. Moreover, levels of superoxide and
      matrix metalloproteinase-9 were greater in SOD1(-/-) mice than wild-type
      littermates after induction of ICH. Active matrix metalloproteinases colocalized
      on cerebral vessels that appeared to lead toward regions with ICH. CONCLUSIONS:
      These results suggest that superoxide contributes to the pathogenesis of
      spontaneous ICH, possibly through activation of matrix metalloproteinase-9, and
      that SOD1 protects against spontaneous ICH during hypertension.

PMID- 20150549
TI  - Recanalization of vertebral artery dissection.
AB  - BACKGROUND AND PURPOSE: We investigated the predictors and time course for
      recanalization after vertebral artery dissection. METHODS: We prospectively
      studied 61 consecutive patients with confirmed diagnoses of vertebral artery
      dissection without intracerebral hemorrhage. Neuroimaging and clinical follow-up
      were performed at presentation and at 3, 6, and 12 months. RESULTS: We included
      61 patients with confirmed vertebral artery dissection; 19 were evaluated and
      followed up with conventional angiography, 24 with MR angiography, and 18 with CT
      angiography. Fifty-one patients had a stenotic dissection, 7 had an occlusive
      dissection, one had a double-lumen image, and 2 had a pseudoaneurysm. The
      estimated rate of complete recanalization after vertebral artery dissection was
      45.9% at 3 months, 62.3% at 6 months, and 63.9% at 12 months. We found no
      association between outcome and complete or partial recanalization nor did we
      find any factors associated with recanalization. CONCLUSIONS: These results
      suggest that recanalization of vertebral artery dissection occurs mainly within
      the first 6 months after the onset of symptoms regardless of the location or
      pattern of the dissection.

PMID- 20150550
TI  - Drip, ship, and retrieve: cooperative recanalization therapy in acute basilar
      artery occlusion.
AB  - BACKGROUND AND PURPOSE: In acute basilar artery occlusion, intra-arterial
      thrombolysis or endovascular mechanical recanalization may result in higher
      recanalization rates than intravenous thrombolysis. However, many patients are
      admitted to community hospitals, where endovascular therapy is usually not
      readily available. We initiated a "drip, ship, and retrieve" cooperative
      treatment protocol in 2006, in which thrombolysis was initiated in the community
      hospital with simultaneous referral to our stroke center and the use of
      endovascular mechanical recanalization as required. METHODS: The outcome of all
      consecutive patients treated by this protocol between 2006 and June 2009 was
      compared with that of a similar population of referred patients who had received
      primary intra-arterial therapy with or without tirofiban bridging at our center
      between 2003 and 2005. RESULTS: In both groups, 26 patients were identified. The
      rate of symptomatic intracranial hemorrhage was 12% in previous patients and 8%
      in those treated under the new protocol. Recanalization rates were similar: 92%
      in previous patients and 85% with the new protocol; 38% of these had
      recanalization after intravenous thrombolysis alone. Functional outcome was
      better among those treated with the new protocol, with more patients achieving a
      modified Rankin scale score < or = 2 (38% versus 12%; P=0.03) and < or = 3 (50%
      versus 23%; P=0.04). CONCLUSIONS: "Drip, ship, and retrieve" seems to be feasible
      and safe in acute basilar artery occlusion. Patients appear to benefit from
      initiation of intravenous thrombolysis in the community hospital before transfer.
      Randomized controlled trials will have to confirm the expected benefit of
      subsequent on-demand mechanical recanalization on clinical outcome.

PMID- 20150551
TI  - Moxibustion for stroke rehabilitation: systematic review.
AB  - BACKGROUND AND PURPOSE: Positive effects of moxibustion for stroke rehabilitation
      may be seen in real clinical practice. Currently, no systematic reviews are
      available. The aim of this systematic review was to analyze the trial data on the
      effectiveness of moxibustion for stroke rehabilitation. METHODS: Fourteen
      databases were searched without language restriction. Randomized clinical trials
      were included if moxibustion was tested as the sole treatment or as an adjunct to
      other treatments for stroke rehabilitation. RESULTS: Nine randomized clinical
      trials met our inclusion criteria. Three randomized clinical trials reported
      favorable effects of moxibustion plus standard care on motor function versus
      standard care alone (N=142; standardized mean difference=0.72; 95% confidence
      interval, 0.37 to 1.08; P<0.0001). Three randomized clinical trials compared the
      effects of moxibustion on activities of daily living alone but failed to show
      favorable effects of moxibustion. CONCLUSION: This systematic review found
      limited effectiveness of moxibustion as an adjunct to standard care in stroke
      rehabilitation.

PMID- 20150552
TI  - Safety of TCD "bubble study".

PMID- 20150553
TI  - Differing risk factor profiles of ischemic stroke subtypes: evidence for a
      distinct lacunar arteriopathy?
AB  - BACKGROUND AND PURPOSE: Differences in risk factor profiles between lacunar and
      other ischemic stroke subtypes may provide evidence for a distinct lacunar
      arteriopathy, but existing studies have limitations. We overcame these by pooling
      individual data on 2875 patients with first-ever ischemic stroke from 5
      collaborating prospective stroke registers that used similar, unbiased methods to
      define risk factors and classify stroke subtypes. METHODS: We compared risk
      factors between lacunar and nonlacunar ischemic strokes, altering the comparison
      groups in sensitivity analyses, and incorporated these data into a meta-analysis
      of published studies. RESULTS: Unadjusted and adjusted analyses gave similar
      results. We found a lower prevalence of cardioembolic source (adjusted odds
      ratio, 0.33; 95% CI, 0.24 to 0.46), ipsilateral carotid stenosis (odds ratio,
      0.21; 95% CI, 0.14 to 0.30), and ischemic heart disease (odds ratio, 0.75; 95%
      CI, 0.58 to 0.97) in lacunar compared with nonlacunar patients but no difference
      for hypertension, diabetes, or any other risk factor studied. Results were robust
      to sensitivity analyses and largely confirmed in our meta-analysis. CONCLUSIONS:
      Hypertension and diabetes appear equally common in lacunar and nonlacunar
      ischemic stroke, but lacunar stroke is less likely to be caused by embolism from
      the heart or proximal arteries, and the lower prevalence of ischemic heart
      disease in lacunar stroke provides additional support for a nonatherosclerotic
      arteriopathy causing many lacunar ischemic strokes. Our findings have
      implications for how clinicians classify ischemic stroke subtypes and highlight
      the need for additional research into the specific causes of and treatments for
      lacunar stroke.

PMID- 20150554
TI  - Low levels of antibodies against phosphorylcholine predict development of stroke
      in a population-based study from northern Sweden.
AB  - BACKGROUND AND PURPOSE: Natural immunoglobulin M antibodies specific for
      phosphorylcholine (anti-PC) have been implicated in atherosclerosis. We have
      shown previously that high levels of anti-PC predict a slower progression of
      atherosclerosis in humans and that low levels of anti-PC are associated with
      higher risk for cardiovascular disease. Here we determine the association between
      anti-PC and the incidence of stroke. METHODS: Using a nested case control study
      design, we examined 227 incident cases (125 men and 102 women) of first-time
      stroke and 455 age- and sex-matched controls identified during a 13-year time
      period (1985 to 1999) within the population-based cohorts of the Vasterbotten
      Intervention Project (VIP) and the World Health Organization Monitoring Trends
      and Determinants in Cardiovascular Disease (WHO MONICA) project in Northern
      Sweden. Odds ratios of stroke with 95% CIs with adjustments for age, gender,
      smoking, serum cholesterol, diabetes, body mass index, and blood pressure were
      determined. Anti-PC levels were measured using ELISA. RESULTS: A significant
      association between low levels of anti-PC at baseline and incident stroke was
      seen for the whole group of anti-PC levels below the 30th percentile
      (multivariately adjusted odds ratio, 1.62; CI, 1.11 to 2.35). Analyses of gender
      specific associations indicated fairly strong associations for females,
      especially at the lowest 30th percentile (multivariately adjusted odds ratio,
      2.65; CI, 1.41 to 4.95). No associations were noted for men. CONCLUSION: Low anti
      PC is a novel independent risk marker for development of stroke. Measurements of
      anti-PC could be used to identify immunodeficient subjects at an increased risk
      for stroke. The possibility that such subjects might be targets for novel modes
      of treatment such as immunotherapies deserves further investigation.

PMID- 20150555
TI  - TRAIL promotes VSMC proliferation and neointima formation in a FGF-2-, Sp1
      phosphorylation-, and NFkappaB-dependent manner.
AB  - RATIONALE: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is
      well reported as an inducer of apoptosis in tumor models; however, its role and
      function in vivo in atherosclerosis and vascular injury has not been established.
      OBJECTIVE: We sought to study the function of TRAIL in cardiovascular pathology
      and its regulation in vivo. METHODS AND RESULTS: Here, we show that TRAIL was
      upregulated in medial vascular smooth muscle cells (VSMCs) 24 hours following
      perivascular cuff placement around femoral arteries of mice. We also show that
      TRAIL mRNA and promoter activity was induced in VSMCs following in vitro
      mechanical injury. Intimal thickening 15 days after cuff placement was reduced 2-
      to 3-fold in TRAIL(-/-) compared to wild-type mice and was reversible by
      administration of recombinant TRAIL. Additionally, reduced VSMC proliferation was
      observed in injured arteries of TRAIL(-/-) mice. Fibroblast growth factor (FGF)
      2, a potent growth factor released following vascular injury, was also reduced in
      arteries of TRAIL(-/-) mice, and VSMCs isolated from these animals did not
      respond to FGF-2 in vitro. Injury and FGF-2 regulated TRAIL transcriptional
      activity via 2 specificity protein (Sp)1 elements in the proximal TRAIL promoter,
      a binding site also shared by nuclear factor (NF)kappaB. Mutational studies
      confirmed a role for Sp1 in injury- and FGF-2-inducible TRAIL transcription.
      Furthermore, increased NFkappaB expression after injury transactivated the TRAIL
      promoter. Interestingly, following mechanical injury, Sp1 phosphorylation
      (Thr453) and an increase in the physical interaction of p-Sp1(Thr453) with
      NFkappaB was observed. CONCLUSIONS: We conclude that TRAIL induction involves FGF
      2, Sp1-phosphorylation and NFkappaB and that TRAIL promotes VSMC proliferation
      and neointima formation after arterial injury.

PMID- 20150556
TI  - Nonalcoholic fatty liver disease as the transducer of hepatic oversecretion of
      very-low-density lipoprotein-apolipoprotein B-100 in obesity.
AB  - OBJECTIVE: To examine the association between liver fat content and very low
      density lipoprotein (VLDL)-apolipoprotein (apo) B-100 kinetics and the
      corresponding responses to weight loss in obese subjects. METHODS AND RESULTS:
      VLDL-apoB-100 kinetics were assessed using stable isotope tracers, and the fat
      content of the liver and abdomen was determined by magnetic resonance techniques
      in 25 obese subjects. In univariate analysis, liver fat content was significantly
      (P<0.05 in all) associated with body mass index (r=0.65), visceral fat area
      (r=0.45), triglycerides (r=0.40), homeostasis model assessment score (r=0.40),
      VLDL-apoB-100 concentrations (r=0.44), and secretion rate (r=0.45). However,
      liver fat content was not associated with plasma concentrations of retinol
      binding protein 4, fetuin A, adiponectin, interleukin-6, and tumor necrosis
      factor-alpha. Of these 25 subjects, 9 diagnosed as having nonalcoholic fatty
      liver disease (which is highly prevalent in obese individuals and strongly
      associated with dyslipidemia) underwent a weight loss program. The low-fat diet
      achieved significant reduction in body weight, body mass index, liver fat,
      visceral and subcutaneous fat areas, homeostasis model assessment score,
      triglycerides, VLDL-apoB-100 concentrations, and VLDL-apoB-100 secretion rate.
      The percentage reduction of liver fat with weight loss was significantly
      associated with the corresponding decreases in VLDL-apoB-100 secretion (r=0.67)
      and visceral fat (r=0.84). CONCLUSION: In patients with obesity, hepatic
      steatosis increases VLDL-apoB-100 secretion. Weight loss can help reduce this
      abnormality.

PMID- 20150557
TI  - Macrophage LRP-1 controls plaque cellularity by regulating efferocytosis and Akt
      activation.
AB  - OBJECTIVE: The balance between apoptosis susceptibility and efferocytosis of
      macrophages is central to plaque remodeling and inflammation. LRP-1 and its
      ligand, apolipoprotein E, have been implicated in efferocytosis and apoptosis in
      some cell types. We investigated the involvement of the macrophage LRP
      1/apolipoprotein E axis in controlling plaque apoptosis and efferocytosis. Method
      and Results- LRP-1(-/-) macrophages displayed nearly 2-fold more TUNEL positivity
      compared to wild-type cells in the presence of DMEM alone or with either
      lipopolysaccharide or oxidized low-density lipoprotein. The survival kinase,
      phosphorylated Akt, was barely detectable in LRP-1(-/-) cells, causing decreased
      phosphorylated Bad and increased cleaved caspase-3. Regardless of the apoptotic
      stimulation and degree of cell death, LRP-1(-/-) macrophages displayed enhanced
      inflammation with increased IL-1 beta, IL-6, and tumor necrosis factor-alpha
      expression. Efferocytosis of apoptotic macrophages was reduced by 60% in LRP-1(-/
      ) vs wild-type macrophages despite increased apolipoprotein E expression by both
      LRP-1(-/-) phagocytes and wild-type apoptotic cells. Compared to wild-type
      macrophage lesions, LRP-1(-/-) lesions had 5.7-fold more necrotic core with more
      dead cells not associated with macrophages. CONCLUSIONS: Macrophage LRP-1
      deficiency increases cell death and inflammation by impairing phosphorylated Akt
      activation and efferocytosis. Increased apolipoprotein E expression in LRP-1(-/-)
      macrophages suggests that the LRP-1/apolipoprotein E axis regulates the balance
      between apoptosis and efferocytosis, thereby preventing necrotic core formation.

PMID- 20150558
TI  - Genome-wide association study identifies variants at the IL18-BCO2 locus
      associated with interleukin-18 levels.
AB  - OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the
      processes of innate and acquired immunities and associated with cardiovascular
      disease and type 2 diabetes. We sought to identify the common genetic variants
      associated with IL-18 levels. METHODS AND RESULTS: We performed a 2-stage genome
      wide association study among women of European ancestry from the Nurses' Health
      Study (NHS) and Women's Genome Health Study (WGHS). IL-18 levels were measured by
      ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide polymorphisms
      (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1
      x 10(-5) significance level. The strongest association was found for SNP
      rs2115763 in the BCO2 gene (P=6.31 x 10(-8)). In silico replication in WGHS (435
      women) confirmed these findings. The combined analysis of the 2 studies indicated
      that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance
      level (P<5 x 10(-8)). Forward selection analysis indicated that SNPs rs2115763
      and rs1834481 were independently associated with IL-18 levels (P=0.0002 and
      0.0006, respectively). The 2 SNPs together explained 2.9% of variation of plasma
      IL-18 levels. CONCLUSIONS: This study identified several novel variants at the
      IL18-BCO2 locus associated with IL-18 levels.

PMID- 20150559
TI  - CREB downregulation in vascular disease: a common response to cardiovascular
      risk.
AB  - OBJECTIVE: To examine the impact of low-density lipoprotein (LDL), an established
      mediator of atherosclerosis, on the transcription factor cAMP-response element
      binding protein (CREB), which is a regulator of vascular smooth muscle cell
      (VSMC) quiescence. METHODS AND RESULTS: VSMC CREB content is diminished in rodent
      models of diabetes and pulmonary hypertension. We examined aortic CREB content in
      rodent models of aging, hypertension, and insulin resistance, and we determined
      nuclear CREB protein in the medial VSMC of high-fat-fed LDL receptor-null mice.
      There was significant loss of CREB protein in all models. In vitro, primary
      culture rat aortic VSMC exposed to LDL and oxidized LDL exhibited a rapid,
      transient increase in CREB phosphorylation and transient
      phosphorylation/activation of Akt, ERK, JNK, ans p38 MAPK. Exposure to oxidized
      LDL, but not to LDL, for 24 to 48 hours decreased CREB protein in a dose
      dependent fashion and led to nuclear exclusion of CREB. Pharmacological reactive
      oxygen species scavengers and inhibition of ERK activation blocked oxidized LDL
      mediated CREB downregulation. CONCLUSIONS: These data support a model wherein
      loss of VSMC CREB protein, which renders these cells more susceptible to
      activation and apoptosis, is a common pathological response to vascular injury
      and potentially contributes to plaque progression.

PMID- 20150560
TI  - Rheumatic disease and carotid intima-media thickness: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis to examine whether
      rheumatic disease is associated with an increased carotid intima-media thickness
      (CIMT; increasingly used as a surrogate marker for atherosclerosis) when compared
      with healthy control subjects. METHODS AND RESULTS: A prespecified search
      strategy was used to identify relevant studies in the MEDLINE and EMBASE
      databases (January 1, 1986 to December 31, 2008). Methodological quality was
      assessed using the Newcastle-Ottawa score for observational studies. A total of
      68 controlled comparisons from 60 different studies were reviewed: 25 (37%) on
      rheumatoid arthritis, 24 (35%) on systemic lupus erythematosus, 6 (9%) on
      systemic sclerosis, and 13 (19%) on other rheumatic diseases. Random-effects meta
      regression analysis was performed. The estimated summary effect size between
      control and study subject CIMT measurement comparisons, with preexisting
      cardiovascular disease excluded, was 0.64 (95% CI, 0.46 to 0.82). This
      represented an overall absolute mean difference of 0.06 mm (95% CI, 0.05 to 0.06
      mm). Preexisting cardiovascular disease, rheumatic disease type, and disease
      duration contributed to heterogeneity. CONCLUSION: Accelerated atherosclerosis is
      a common complication of autoimmune rheumatic diseases, with early changes seen
      even in pediatric patients. CIMT was significantly increased in rheumatic disease
      populations. Future studies need to use a standardized protocol to ensure
      clinically meaningful results when measuring CIMT as a surrogate for premature
      atherosclerosis.

PMID- 20150561
TI  - Enhanced external counterpulsation attenuates atherosclerosis progression through
      modulation of proinflammatory signal pathway.
AB  - OBJECTIVE: Shear stress may be the most crucial local factor affecting
      atherogenesis. The present study investigated the effect of exposure to increased
      shear stress promoted by enhanced external counterpulsation (EECP) on the
      progression of atherosclerosis and the underlying inflammation-related molecular
      mechanisms in a porcine model of hypercholesterolemia. METHODS AND RESULTS:
      Hypercholesterolemic pigs were subjected to a 7-week EECP intervention while
      being fed a high-cholesterol diet. EECP resulted in a 34.38% increase of mean
      wall shear stress and a significantly lower pulsatility index in the brachial
      artery. The animals receiving EECP showed a marked reduction in atherosclerotic
      lesion size in the coronary artery and abdominal aorta compared with the
      hypercholesterolemic control group, associated with a decrease in macrophage
      accumulation. The expression of a set of genes involved in inflammation
      (including C-reactive protein [CRP], complement 3a, vascular cell adhesion
      molecule-1 [VCAM-1], and inducible nitric oxide synthase), mitogen-activated
      protein kinase (MAPK)-p38 phosphorylation, and nuclear factor-kappaB (NF-kappaB)
      activation, was attenuated. CONCLUSIONS: These findings suggested that long-term
      EECP exerts a retarding effect on atherosclerosis by downregulating
      proinflammatory gene expression. The underlying mechanisms are related to chronic
      exposure to increased pulsatile shear stress promoted by EECP; this exposure
      suppresses the overactivation of the MAPK-P38/NF-kappaB/VCAM-1 signaling pathway
      induced by hypercholesterolemia.

PMID- 20150562
TI  - Speeding of VO2 kinetics with endurance training in old and young men is
      associated with improved matching of local O2 delivery to muscle O2 utilization.
AB  - The time course and mechanisms of adjustment of pulmonary oxygen uptake (V(O(2)))
      kinetics (time constant tauV(O(2p))) were examined during step transitions from
      20 W to moderate-intensity cycling in eight older men (O; 68 +/- 7 yr) and eight
      young men (Y; 23 +/- 5 yr) before training and at 3, 6, 9, and 12 wk of endurance
      training. V(O(2p)) was measured breath by breath with a volume turbine and a mass
      spectrometer. Changes in deoxygenated hemoglobin concentration (Delta[HHb]) were
      measured by near-infrared spectroscopy. V(O(2p)) and Delta[HHb] were modeled with
      a monoexponential model. Training was performed on a cycle ergometer three times
      per week for 45 min at approximately 70% of peak V(O(2)). Pretraining tauV(O(2p))
      was greater (P < 0.05) in O (43 +/- 10 s) than Y (34 +/- 8 s). tauV(O(2p))
      decreased (P < 0.05) by 3 wk of training in both O (35 +/- 9 s) and Y (22 +/- 8
      s), with no further changes thereafter. The pretraining overall adjustment of
      Delta[HHb] was faster than tauV(O(2p)) in both O and Y, resulting in
      Delta[HHb]/V(O(2p)) displaying an "overshoot" during the transient relative to
      the subsequent steady-state level. After 3 wk of training the Delta[HHb]/V(O(2p))
      overshoot was attenuated in both O and Y. With further training, this overshoot
      persisted in O but was eliminated after 6 wk in Y. The training-induced speeding
      of V(O(2p)) kinetics in O and Y at 3 wk of training was associated with an
      improved matching of local O(2) delivery to muscle V(O(2)) (as represented by a
      lower Delta[HHb]/V(O(2p))). The continued overshoot in Delta[HHb]/V(O(2p)) in O
      may reflect a reduced vasodilatory responsiveness that may limit muscle blood
      flow distribution during the on-transient of exercise.

PMID- 20150563
TI  - Hypercapnia causes cellular oxidation and nitrosation in addition to acidosis:
      implications for CO2 chemoreceptor function and dysfunction.
AB  - Cellular mechanisms of CO2 chemoreception are discussed and debated in terms of
      the stimuli produced during hypercapnic acidosis and their molecular targets:
      protons generated by the hydration of CO2 and dissociation of carbonic acid,
      which target membrane-bound proteins and lipids in brain stem neurons. The CO2
      hydration reaction, however, is not the only reaction that CO2 undergoes that
      generates molecules capable of modifying proteins and lipids. Molecular CO2 also
      reacts with peroxynitrite (ONOO-), a reactive nitrogen species (RNS), which is
      produced from nitric oxide (*NO) and superoxide (*O2-). The CO2/ONOO- reaction,
      in turn, produces additional nitrosative and oxidative reactive intermediates.
      Furthermore, protons facilitate additional redox reactions that generate other
      reactive oxygen species (ROS). ROS/RNS generated by these redox reactions may act
      as additional stimuli of CO2 chemoreceptors since neurons in chemosensitive areas
      produce both *NO and *O2- and, therefore, ONOO-. Perturbing *NO, *O2-, and ONOO-
      activities in chemosensitive areas modulates cardiorespiration. Moreover, neurons
      in at least one chemosensitive area, the solitary complex, are stimulated by
      cellular oxidation. Together, these data raise the following two questions: 1) do
      pH and ROS/RNS work in tandem to stimulate CO2 chemoreceptors during hypercapnic
      acidosis; and 2) does nitrosative stress and oxidative stress contribute to CO2
      chemoreceptor dysfunction? To begin considering these two issues and their
      implications for central chemoreception, this minireview has the following three
      goals: 1) summarize the nitrosative and oxidative reactions that occur during
      hypercapnic acidosis and isocapnic acidosis; 2) review the evidence that redox
      signaling occurs in chemosensitive areas; and 3) review the evidence that neurons
      in the solitary complex are stimulated by cellular oxidation.

PMID- 20150564
TI  - Preinspiratory and inspiratory hypoglossal motor output during hypoxia-induced
      plasticity in the rat.
AB  - Respiratory-related discharge in the hypoglossal (XII) nerve is composed of
      preinspiratory (pre-I) and inspiratory (I) activity. Our first purpose was to
      test the hypothesis that hypoxia-induced plasticity in XII motor output is
      differentially expressed in pre-I vs. I XII bursting. Short-term potentiation
      (STP) of XII motor output was induced in urethane-anesthetized, vagotomized, and
      ventilated rats by exposure to isocapnic hypoxia (PaO2 of approximately 35 Torr).
      Both pre-I and I XII discharge abruptly increased at beginning of hypoxia (i.e.,
      acute hypoxic response), and the relative increase in amplitude was much greater
      for pre-I (507+/-46% baseline) vs. I bursting (257+/-16% baseline; P<0.01). In
      addition, STP was expressed in I but not pre-I bursting following hypoxia.
      Specifically, I activity remained elevated following termination of hypoxia but
      pre-I bursting abruptly returned to prehypoxia levels. Our second purpose was to
      test the hypothesis that STP of I XII activity results from recruitment of
      inactive or "silent" XII motoneurons (MNs) vs. rate coding of active MNs. Single
      fiber recordings were used to classify XII MNs as I, expiratory-inspiratory, or
      silent based on baseline discharge patterns. STP of I XII activity following
      hypoxia was associated with increased discharge frequency in active I and silent
      MNs but not expiratory-inspiratory MNs. We conclude that the expression of
      respiratory plasticity is differentially regulated between pre-I and I XII
      activity. In addition, both recruitment of silent MNs and rate coding of active I
      MNs contribute to increases in XII motor output following hypoxia.

PMID- 20150565
TI  - Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein
      synthesis in older men.
AB  - The loss of skeletal muscle mass during aging, sarcopenia, increases the risk for
      falls and dependence. Resistance exercise (RE) is an effective rehabilitation
      technique that can improve muscle mass and strength; however, older individuals
      are resistant to the stimulation of muscle protein synthesis (MPS) with
      traditional high-intensity RE. Recently, a novel rehabilitation exercise method,
      low-intensity RE, combined with blood flow restriction (BFR), has been shown to
      stimulate mammalian target of rapamycin complex 1 (mTORC1) signaling and MPS in
      young men. We hypothesized that low-intensity RE with BFR would be able to
      activate mTORC1 signaling and stimulate MPS in older men. We measured MPS and
      mTORC1-associated signaling proteins in seven older men (age 70+/-2 yr) before
      and after exercise. Subjects were studied identically on two occasions: during
      BFR exercise [bilateral leg extension exercise at 20% of 1-repetition maximum (1
      RM) with pressure cuff placed proximally on both thighs and inflated at 200 mmHg]
      and during exercise without the pressure cuff (Ctrl). MPS and phosphorylation of
      signaling proteins were determined on successive muscle biopsies by stable
      isotopic techniques and immunoblotting, respectively. MPS increased 56% from
      baseline after BFR exercise (P<0.05), while no change was observed in the Ctrl
      group (P>0.05). Downstream of mTORC1, ribosomal S6 kinase 1 (S6K1)
      phosphorylation and ribosomal protein S6 (rpS6) phosphorylation increased only in
      the BFR group after exercise (P<0.05). We conclude that low-intensity RE in
      combination with BFR enhances mTORC1 signaling and MPS in older men. BFR exercise
      is a novel intervention that may enhance muscle rehabilitation to counteract
      sarcopenia.

PMID- 20150567
TI  - Acute cardiac effects of marathon running.
AB  - We sought to clarify the significance of cardiac dysfunction and to assess its
      relationship with elevated biomarkers by using cardiovascular magnetic resonance
      imaging in healthy, middle-aged subjects immediately after they ran 26.2 miles.
      Cardiac dysfunction and elevated blood markers of myocardial injury have been
      reported after prolonged strenuous exercise. From 425 volunteers, 13 women and 12
      men were randomly selected, provided medical and training history, and underwent
      baseline cardiopulmonary exercise testing to exhaustion. Blood biomarkers,
      cardiovascular magnetic resonance imaging, and 24-h ambulatory
      electrocardiography were performed 4 wk before and immediately after the race.
      Participants were 38.7+/-9.0 yr old, had baseline peak oxygen consumption of
      52.9+/-5.6 ml.kg(-1).min(-1), and completed the marathon in 256.2+/-43.5 min.
      Cardiac troponin I and B-type natriuretic peptide increased following the race
      (P=0.001 and P<0.0001, respectively). Cardiovascular magnetic resonance
      determined pre- and postmarathon left ventricular ejection fractions were
      comparable, 57.7+/-4.1% and 58.7+/-4.3%, respectively (P=0.32). Right atrial
      volume index increased from 46.7+/-14.4 to 57.0+/-14.5 ml/m2 (P<0.0001).
      Similarly, right ventricular end-systolic volume index increased from 47.4+/-11.2
      to 57.0+/-14.6 ml/m2 (P<0.0001) whereas the right ventricular ejection fraction
      dropped from 53.6+/-7.1 to 45.5+/-8.5% (P<0.0001). There were no morphological
      changes observed in the left atrium or ventricle or evidence of ischemic injury
      to any chamber by late gadolinium enhancement. There were no significant
      arrhythmias. Marathon running causes dilation of the right atrium and right
      ventricle, reduction of right ventricular ejection fraction, and release of
      cardiac troponin I and B-type natriuretic peptide but does not appear to result
      in ischemic injury to any chamber.

PMID- 20150566
TI  - Hyperoxia attenuates muscle sympathetic nerve activity following isocapnic
      hypoxia in humans.
AB  - Hypoxia may sensitize the carotid chemoreceptors, resulting in a sustained
      elevation of muscle sympathetic nerve activity (MSNA) that outlasts the hypoxic
      stimulus. To test this hypothesis, we determined the effect of carotid body
      inhibition on the sustained elevation of MSNA following isocapnic hypoxia in
      humans. Seven healthy subjects (5 male, 2 female) breathed 100% O(2) (hyperoxia)
      for 1 min before (2 interventions) and after (2-3 interventions) 20 min of
      isocapnic hypoxia (80% arterial oxyhemoglobin saturation). MSNA was continuously
      recorded from the common peroneal nerve with microneurography. There was no
      effect of hyperoxia on MSNA before exposure to isocapnic hypoxia. During the
      isocapnic hypoxia exposure, there was an increase in minute ventilation and heart
      rate that subsided once hypoxia was terminated. In contrast, there was an
      increase in MSNA burst frequency that persisted for approximately 25 min after
      cessation of the stimulus. Hyperoxia resulted in a transient reduction in MSNA
      burst frequency of 28% (P < 0.05), 15% (P < 0.05), and 9% (P > 0.05) in the three
      posthypoxia interventions, respectively. Our results suggest that input from the
      carotid chemoreceptors is obligatory for the sustained elevation of MSNA
      initiated by chemoreflex stimulation. We attribute the decrease in MSNA to a
      transient hyperoxia-induced attenuation of carotid chemoreceptor sensitivity.

PMID- 20150568
TI  - An unbiased stereological method for efficiently quantifying the innervation of
      the heart and other organs based on total length estimations.
AB  - Quantitative information about the innervation is essential to analyze the
      structure-function relationships of organs. So far, there has been no unbiased
      stereological tool for this purpose. This study presents a new unbiased and
      efficient method to quantify the total length of axons in a given reference
      volume, illustrated on the left ventricle of the mouse heart. The method is based
      on the following steps: 1) estimation of the reference volume; 2) randomization
      of location and orientation using appropriate sampling techniques; 3) counting of
      nerve fiber profiles hit by a defined test area within an unbiased counting frame
      on paraffin sections stained immunohistochemically for protein gene product 9.5;
      4) electron microscopic estimation of the mean number of axon profiles contained
      in one nerve fiber profile; 5) estimation of the degree of tissue shrinkage of
      specimens in paraffin; and 6) calculation of the total axon length within the
      reference volume, taking tissue shrinkage into account. In a set of five mouse
      hearts, the total length of axons ramifying between cardiomyocytes ranged between
      approximately 50 and 100 m, with a mean of 75.98 m (SD 23.73). The time required
      for the microscopical analysis was approximately 8 h/animal for an experienced
      observer. Using antibodies specific for different neuron subtypes and
      immunoelectron microscopy, this method is also suited to estimate the total axon
      length of neurons expressing different transmitters. This new and efficient
      method is particularly useful when structural remodeling takes place and is
      suspected to involve gain or loss of axons.

PMID- 20150570
TI  - The impact of the endothelin type A receptor on regional endothelin-1 turnover,
      in particular renal endothelin-1 release, in humans.
AB  - The endothelin type A (ETA) receptor was studied in six healthy subjects on two
      occasions with or without an ETA receptor (BQ-123) blockade. At 40 min of either
      BQ-123 or NaCl infusion, a concomitant infusion of the endothelin-1 (ET-1)
      precursor, big ET-1, was initiated to augment ET-1 formation. Blood samples were
      taken from catheters in a peripheral artery, the renal and femoral veins, and the
      pulmonary artery. Forty minutes of infusion with BQ-123 alone increased heart
      rate (P<0.001) and cardiac output (CO; P<0.01) and depressed mean arterial blood
      pressure (P<0.001) and systemic vascular resistance (SVR; P<0.01). During
      infusion of big ET-1 alone, CO, stroke volume, and renal blood flow decreased
      (P<0.01), whereas SVR and pulmonary and renal vascular resistance increased
      (P<0.05). These responses to big ET-1 were abolished or diminished by BQ-123.
      Renal ET-1 release was threefold higher when big ET-1 infusion was preceded by BQ
      123 infusion (P<0.001). Arterial ET-1 concentrations rose to similar levels after
      big ET-1 infusion (P<0.01) in both trials because of elevated concomitant
      pulmonary uptake (P<0.05) after ETA blockade. Although there was no net ET-1 leg
      exchange, leg ET-1 turnover was higher after big ET-1 was preceded by BQ-123.
      Gene expression of endothelin-converting enzyme 1 and ET-1 in skeletal muscle
      remained unaltered on both occasions. Our data demonstrate that the level of
      circulating ET-1 is regulated by ETA receptor-mediated negative feedback. This
      mechanism seems to be coupled to increased conversion of big ET-1 and is most
      potent in the kidneys. This emphasizes the important physiological role of ETA
      receptors in the kidneys, and the lung seems to be mainly a clearing organ for ET
      1.

PMID- 20150569
TI  - Significant blood resistance to nitric oxide transfer in the lung.
AB  - Lung diffusing capacity for nitric oxide (DLNO) is used to measure alveolar
      membrane conductance (DMNO), but disagreement remains as to whether DMNO=DLNO,
      and whether blood conductance (thetaNO)=infinity. Our previous in vitro and in
      vivo studies suggested that thetaNO<infinity. We now show in a membrane
      oxygenator model perfused with whole blood that addition of a cell-free bovine
      hemoglobin (Hb) glutamer-200 solution increased diffusing capacity of the circuit
      (D) for NO (DNO) by 39%, D for carbon monoxide (DCO) by 24%, and the ratio of DNO
      to DCO by 12% (all P<0.001). In three anesthetized dogs, DLNO and DLCO were
      measured by a rebreathing technique before and after three successive equal
      volume-exchange transfusions with bovine Hb glutamer-200 (10 ml/kg each, total
      exchange 30 ml/kg). At baseline, DLNO/DLCO=4.5. After exchange transfusion, DLNO
      rose 57+/-16% (mean+/-SD, P=0.02) and DLNO/DLCO=7.1, whereas DLCO remained
      unchanged. Thus, in vitro and in vivo data directly demonstrate a finite thetaNO.
      We conclude that the erythrocyte and/or its immediate environment imposes
      considerable resistance to alveolar-capillary NO uptake. DLNO is sensitive to
      dynamic hematological factors and is not a pure index of conductance of the
      alveolar tissue membrane. With successive exchange transfusion, the estimated in
      vivo thetaNO [5.1 ml NO.(ml blood.min.Torr)(-1)] approached 4.5 ml NO.(ml
      blood.min.Torr)(-1), which was derived from in vitro measurements by Carlsen and
      Comroe (J Gen Physiol 42: 83-107, 1958). Therefore, we suggest use of thetaNO=4.5
      ml NO.(min.Torr.ml blood)(-1) for calculation of DM(NO) and pulmonary capillary
      blood volume from DLNO and DLCO.

PMID- 20150571
TI  - Central CO2 chemoreception in cardiorespiratory control.

PMID- 20150572
TI  - Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first
      line therapy for nonsquamous non-small-cell lung cancer: results from a
      randomised phase III trial (AVAiL).
AB  - BACKGROUND: Bevacizumab, the anti-vascular endothelial growth factor agent,
      provides clinical benefit when combined with platinum-based chemotherapy in first
      line advanced non-small-cell lung cancer. We report the final overall survival
      (OS) analysis from the phase III AVAiL trial. PATIENTS AND METHODS: Patients (n =
      1043) received cisplatin 80 mg/m(2) and gemcitabine 1250 mg/m(2) for up to six
      cycles plus bevacizumab 7.5 mg/kg (n = 345), bevacizumab 15 mg/kg (n = 351) or
      placebo (n = 347) every 3 weeks until progression. Primary end point was
      progression-free survival (PFS); OS was a secondary end point. RESULTS:
      Significant PFS prolongation with bevacizumab compared with placebo was
      maintained with longer follow-up {hazard ratio (HR) [95% confidence interval
      (CI)] 0.75 (0.64-0.87), P = 0.0003 and 0.85 (0.73-1.00), P = 0.0456} for the 7.5
      and 15 mg/kg groups, respectively. Median OS was >13 months in all treatment
      groups; nevertheless, OS was not significantly increased with bevacizumab [HR
      (95% CI) 0.93 (0.78-1.11), P = 0.420 and 1.03 (0.86-1.23), P = 0.761] for the 7.5
      and 15 mg/kg groups, respectively, versus placebo. Most patients ( approximately
      62%) received multiple lines of poststudy treatment. Updated safety results are
      consistent with those previously reported. CONCLUSIONS: Final analysis of AVAiL
      confirms the efficacy of bevacizumab when combined with cisplatin-gemcitabine.
      The PFS benefit did not translate into a significant OS benefit, possibly due to
      high use of efficacious second-line therapies.

PMID- 20150573
TI  - A prognostic model in patients treated for metastatic gastric cancer with second
      line chemotherapy.
AB  - BACKGROUND: This retrospective study was carried out to evaluate the prognostic
      significance of clinical factors in patients treated for metastatic gastric
      cancer with second-line chemotherapy. PATIENTS AND METHODS: We evaluated the
      prognostic significance of various clinical factors in 126 patients, who were
      treated with second-line chemotherapy. RESULTS: Median progression-free and
      overall survival (OS) for second-line chemotherapy were 3.3 and 5.3 months,
      respectively, with an overall response rate of 11.1%. Multivariate analysis
      identified three independent prognostic factors: performance status: Eastern
      Cooperative Oncology Group zero to one [hazard ratio (HR) 2.3, 95% confidence
      interval (CI) 1.7-5.4], hemoglobin (Hb) level: >/=10 g/dl (HR 2.2, 95% CI 2.1
      2.4) and time-to-progression (TTP) under first-line therapy: >/=5 months (HR 0.5,
      95% CI 0.3-0.8). From the obtained data, a prognostic index was constructed,
      dividing the patients into three risk groups: good (n = 40), intermediate (n =
      36) and poor risk group (n = 56). The median survival for good, intermediate and
      poor risk groups were 13.5, 6.0 and 2.9 months, respectively, whereas the 1-year
      OS rates were 50.2%, 14.2% and 2.6%, respectively (P = 0.00001). CONCLUSIONS:
      With inadequate data from randomized controlled trials at the moment, our report
      indicates that second-line chemotherapy is effective and beneficial in patients
      with good performance status, higher Hb level along with higher TTP under first
      line therapy.

PMID- 20150574
TI  - Mosaicism in osteopathia striata with cranial sclerosis.
AB  - CONTEXT: Osteopathia striata with cranial sclerosis is an X-linked dominant
      condition caused by mutations in the WTX gene, resulting in linear striations in
      long bones in combination with cranial sclerosis. This condition is usually
      lethal in males. OBJECTIVE/PATIENT: Our aim was to determine the underlying
      genetic cause in a 37-yr-old male with this condition. DESIGN: DNA sequencing of
      peripheral blood and hair was performed to identify mutations in WTX.
      Quantitative PCR was performed to determine gene copy number variation. RESULTS:
      DNA sequenced from peripheral blood revealed the presence of two alleles at the
      1108th position of the WTX gene. Subsequent DNA sequencing of hair follicles and
      quantitative PCR confirmed the presence of mosaicism. CONCLUSION: A novel
      mutation (c.1108G>T) found in our patient results in a truncated protein (E370X).
      Our patient represents the first confirmed case of mosaicism in osteopathia
      striata with cranial sclerosis.

PMID- 20150575
TI  - Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of
      59 patients with a 46,XY disorder of sex development.
AB  - BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of
      46,XY disorders of sex development (DSD) and are associated with a variety of
      phenotypes, ranging from phenotypic women [complete androgen insensitivity
      syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or
      men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study
      was to characterize the contribution of the AR gene to the molecular cause of
      46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133
      index patients with 46,XY DSD in whom gonads were differentiated as testes, with
      phenotypes including varying degrees of undervirilization, and in whom the AR
      gene was the first candidate for a molecular analysis. METHODS: The AR gene was
      sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in
      family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations
      were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were
      CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located
      in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty
      three mutations (40.4%) had been previously described and 34 (59.6%) were novel.
      CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a
      clearly higher frequency in the complete phenotype. Mutations spread along the
      whole coding sequence, including exon 1. This series shows that 60% of mutations
      detected during the period 2002-2009 were novel.

PMID- 20150576
TI  - Serum anti-mullerian hormone concentrations are elevated in oligomenorrheic girls
      without evidence of hyperandrogenism.
AB  - CONTEXT: Serum anti-Mullerian hormone (AMH) levels are significantly elevated in
      adolescents with polycystic ovary syndrome (PCOS) compared to normal controls.
      Whether adolescents with oligomenorrhea have elevated AMH levels is unknown.
      OBJECTIVE: This study was performed to assess serum AMH levels in oligomenorrheic
      (OLIGO) girls without evidence of hyperandrogenism. DESIGN: This was a
      prospective study comparing AMH levels in OLIGO, PCOS, and normal control
      adolescents. SETTING: The study was conducted through four tertiary academic
      medical centers. PARTICIPANTS: The study groups were comprised of OLIGO (n = 24),
      PCOS (n = 153), and normal adolescent girls (n = 39), as well as PCOS (n = 73)
      and normal adult women (n = 36). INTERVENTIONS: In each subject, serum AMH levels
      were assessed in the early to midfollicular phases for regularly menstruating
      subjects and on an arbitrary day for OLIGO or PCOS subjects. MAIN OUTCOME
      MEASURE(S): Basal serum AMH levels were assessed among OLIGO, PCOS, and normal
      girls, in addition to PCOS and normal women. RESULTS: OLIGO girls had serum AMH
      levels (5.33 +/- 0.47 ng/ml) that were significantly greater than the normal
      adolescents (3.05 +/- 0.31 ng/ml) and adults (2.33 +/- 0.22 ng/ml), but similar
      to values seen in the PCOS adolescents (5.28 +/- 0.26 ng/ml) and adults (6.36 +/-
      0.47 ng/ml). Obese adolescents and PCOS women had significantly lower AMH levels
      compared to lean controls (P < 0.02). CONCLUSION: In OLIGO adolescents, elevated
      serum AMH levels suggest increased antral follicle number similar to that
      observed in girls with PCOS.

PMID- 20150577
TI  - The effects of exercise-induced weight loss on appetite-related peptides and
      motivation to eat.
AB  - CONTEXT: The magnitude of exercise-induced weight loss depends on the extent of
      compensatory responses. An increase in energy intake is likely to result from
      changes in the appetite control system toward an orexigenic environment; however,
      few studies have measured how exercise impacts on both orexigenic and
      anorexigenic peptides. OBJECTIVE: The aim of the study was to investigate the
      effects of medium-term exercise on fasting/postprandial levels of appetite
      related hormones and subjective appetite sensations in overweight/obese
      individuals. DESIGN AND SETTING: We conducted a longitudinal study in a
      university research center. PARTICIPANTS AND INTERVENTION: Twenty-two sedentary
      overweight/obese individuals (age, 36.9 +/- 8.3 yr; body mass index, 31.3 +/- 3.3
      kg/m(2)) took part in a 12-wk supervised exercise programme (five times per week,
      75% maximal heart rate) and were requested not to change their food intake during
      the study. MAIN OUTCOME MEASURES: We measured changes in body weight and
      fasting/postprandial plasma levels of glucose, insulin, total ghrelin, acylated
      ghrelin (AG), peptide YY, and glucagon-like peptide-1 and feelings of appetite.
      RESULTS: Exercise resulted in a significant reduction in body weight and fasting
      insulin and an increase in AG plasma levels and fasting hunger sensations. A
      significant reduction in postprandial insulin plasma levels and a tendency toward
      an increase in the delayed release of glucagon-like peptide-1 (90-180 min) were
      also observed after exercise, as well as a significant increase (127%) in the
      suppression of AG postprandially. CONCLUSIONS: Exercise-induced weight loss is
      associated with physiological and biopsychological changes toward an increased
      drive to eat in the fasting state. However, this seems to be balanced by an
      improved satiety response to a meal and improved sensitivity of the appetite
      control system.

PMID- 20150578
TI  - The association of mitochondrial content with prevalent and incident type 2
      diabetes.
AB  - CONTEXT: It has been shown that mitochondrial DNA (mtDNA) content is associated
      with type 2 diabetes (T2D) and related traits. However, empirical data, often
      based on small samples, did not confirm this observation in all studies.
      Therefore, the role of mtDNA content in T2D remains elusive. OBJECTIVE: In this
      study, we assessed the heritability of mtDNA content in buccal cells and analyzed
      the association of mtDNA content in blood with prevalent and incident T2D. DESIGN
      AND SETTING: mtDNA content from cells from buccal and blood samples was assessed
      using a real-time PCR-based assay. Heritability of mtDNA content was estimated in
      391 twins from the Netherlands Twin Register. The association with prevalent T2D
      was tested in a case control study from The Netherlands (n = 329). Incident T2D
      was analyzed using prospective samples from Finland (n = 444) and The Netherlands
      (n = 238). MAIN OUTCOME MEASURES: We measured the heritability of mtDNA content
      and the association of mtDNA content in blood with prevalent and incident T2D.
      RESULTS: A heritability of mtDNA content of 35% (19-48%) was estimated in the
      twin families. We did not observe evidence of an association between mtDNA
      content and prevalent or incident T2D and related traits. Furthermore, we
      observed a decline in mtDNA content with increasing age that was male specific (P
      = 0.001). CONCLUSION: In this study, we show that mtDNA content has a
      heritability of 35% in Dutch twins. There is no association between mtDNA content
      in blood and prevalent or incident T2D and related traits in our study samples.

PMID- 20150579
TI  - The incidence of ischemic heart disease and mortality in people with subclinical
      hypothyroidism: reanalysis of the Whickham Survey cohort.
AB  - CONTEXT: The Whickham Survey evaluated vascular events over 20 yr in community
      dwelling subjects stratified by thyroid function and thyroid autoantibody status.
      No association between ischemic heart disease (IHD) and a composite autoimmune
      thyroid disease group, comprising individuals with subclinical hypothyroidism
      (SCH), with positive thyroid antibodies or those using levothyroxine, was found.
      This result appears to be at odds with the findings of other cohort studies.
      OBJECTIVE: The objective of the study was to evaluate incident IHD and mortality
      in participants in relation to their thyroid status. OUTCOMES, DESIGN, AND
      PARTICIPANTS: Data were reanalyzed assessing incident IHD events and mortality
      during 20 yr of follow-up in individuals with endogenous SCH (n = 97; TSH 6.0-15
      mIU/liter) vs. the euthyroid group (n = 2279), who were IHD free at baseline.
      RESULTS: Incident IHD was significantly higher in the SCH group [adjusted hazard
      ratio 1.76 (95% confidence interval 1.15-2.71); P = 0.01]. IHD mortality was also
      increased in the SCH group [hazard ratio of 1.79 (1.02-3.56); P = 0.05]. These
      findings lost their significance when subsequent treatment with levothyroxine was
      excluded from the regression model. There was no difference in all-cause
      mortality between the groups. CONCLUSION: In the Whickham Survey, there is an
      association between incident IHD events and IHD-related mortality with SCH over
      the 20 yr of follow-up. Furthermore, subsequent treatment of SCH with
      levothyroxine appears to attenuate IHD-related morbidity and mortality, and this
      may explain why some other longitudinal studies of SCH have not shown such an
      association; properly designed controlled trials of treatment of SCH are required
      to answer this question definitively.

PMID- 20150580
TI  - Lactation and bone turnover: a conundrum of marked bone loss in the setting of
      coupled bone turnover.
AB  - CONTEXT: Mothers who exclusively breastfeed lose up to 10% of their bone mass.
      This is primarily mediated by PTHrP, in combination with low estrogen levels. The
      mechanisms underlying this marked bone loss are unknown. Uncoupling of bone
      turnover, which is seen in other prototypical states of bone loss, would seem the
      likely explanation. However, the most current markers of bone turnover have not
      been studied in human lactation. OBJECTIVES: The purpose of this study was to
      assess bone formation in lactating humans using the most current bone turnover
      markers. DESIGN AND PARTICIPANTS: We conducted a prospective cohort study with
      repeated measures of bone metabolism in a volunteer sample of 49 women, recruited
      into three study groups: lactating, bottle feeding, and healthy controls. The
      postpartum women were studied at 6-8 and 12-14 wk postpartum, whereas the
      controls were studied at the follicular phase of their menstrual cycles. OUTCOME
      MEASURES: Biochemical markers of bone turnover were assessed. RESULTS: Mean serum
      C-telopeptide of type I collagen, a sensitive marker of bone resorption, was
      approximately 2-fold higher in lactating women as compared with bottle-feeding
      and healthy controls (P = 0.037 and P < 0.001, respectively). Surprisingly, amino
      terminal telopeptides of procollagen 1, the most current marker of bone
      formation, bone-specific alkaline phosphatase, and osteocalcin were all
      significantly higher in the lactating group as compared with controls (P < 0.001,
      P = 0.002, and P < 0.001, respectively). CONCLUSIONS: In contrast to prototypical
      states of rapid bone loss (myeloma, cancer, and immobilization) in which markers
      of bone turnover display marked uncoupling, lactational bone loss, as assessed in
      this small exploratory study, is distinct, showing comparably rapid bone loss in
      the face of apparent osteoclast-osteoblast coupling.

PMID- 20150581
TI  - Epidermal growth factor stimulates human trophoblast cell migration through Rho A
      and Rho C activation.
AB  - This study investigated the roles of Rho protein in epidermal growth factor (EGF)
      induced trophoblast cell migration and its mechanism. Using choriocarcinoma cell
      lines JEG-3 and JAR and first-trimester human chorionic villus explant cultures
      on matrigel, we examined EGF-mediated stimulation of trophoblast migration. EGF
      is shown to have a dose-dependent effect on trophoblast migration. A low
      concentration of EGF (1 ng/ml) has a stimulatory effect on cell migration,
      whereas high concentrations of EGF (100 ng/ml) shows an inhibitory effect. EGF (1
      ng/ml) activates RhoA and RhoC, but not RhoB, through elevated protein levels and
      activity. EGF-induced migration was shown to be inhibited by either cell
      permeable C3 exoenzyme transferase or selective RhoA or RhoC small interfering
      RNAs. The inhibition was not mitigated by the addition of EGF, suggesting that
      RhoA and RhoC play an important role in trophoblast migration and are obligatory
      for EGF action. Treatment of JEG-3 and JAR cells with RhoA small interfering RNA
      induced F-actin cytoskeleton disruption and cell shrinkage, which is consistent
      with the effect of C3 exoenzyme transferase, and this action was not mitigated by
      EGF treatment. RhoC small interfering RNA had no apparent effect on the F-actin
      arrangement, suggesting that RhoA but not RhoC takes part in the EGF-induced
      migration through F-actin rearrangement. These results indicate that RhoA and
      RhoC play more important roles than RhoB in EGF-mediated migration of trophoblast
      cells, and RhoA but not RhoC regulates this migration through F-actin
      cytoskeleton reorganization.

PMID- 20150582
TI  - Outcome and risk factors for mortality in pediatric peritoneal dialysis.
AB  - BACKGROUND: The mortality rate among children requiring renal replacement therapy
      is higher than in children without end-stage renal disease (ESRD). Some factors,
      such as hypoalbuminemia, high peritoneal transport rate, age, malnutrition,
      cardiovascular disease, and recurrent peritonitis, appear to be associated with
      lower survival in adult peritoneal dialysis patients. Data regarding risk factors
      of mortality in children with continuous ambulatory peritoneal dialysis (CAPD)
      are limited. The aims of this study were to analyze the clinical characteristics
      of patients and investigate if routinely used laboratory and clinical variables
      are independent risk factors for mortality in children on CAPD. METHODS: We
      performed a retrospective chart analysis of pediatric ESRD patients on CAPD
      between January 1997 and September 2008. 29 patients undergoing CAPD for more
      than 3 months were enrolled. An analysis was performed on clinical and
      biochemical variables for survivors and nonsurvivors to identify potential risk
      factors for mortality. RESULTS: Mean age was 12.18 +/- 4.57 years. During the
      follow-up period, 8 patients transferred to hemodialysis and 13 patients received
      deceased donor renal transplantation. By the end of the study, 5 patients had
      died. Actuarial survival rate at 2 and 5 years was 96.55% and 91.19%
      respectively. The major complication during therapy was peritonitis (1
      episode/57.79 patient-months). In the univariate analysis, younger age at
      initiation of dialysis, presence of comorbid disease, higher peritoneal transport
      rate, increased protein losses through peritoneal dialysis, high total daily
      protein loss, hypoalbuminemia, and hypophosphatemia were variables associated
      with mortality in pediatric CAPD patients. However, in the multivariate analysis,
      only low serum albumin (b = -2.089, p = 0.006; hazard ratio 8.06, 95% confidence
      interval 0.028 - 0.546) was independently associated with mortality. CONCLUSION:
      Mortality was low in our pediatric patients receiving CAPD. Hypoalbuminemia
      showed a significant association with death in CAPD patients.

PMID- 20150583
TI  - Effect of peritoneal dialysis on abdominal circumference.
AB  - BACKGROUND: Peritoneal dialysis (PD) is probably underused because of fears
      concerning the body image of patients. For the purposes of providing exact
      information for patients when choosing between PD and hemodialysis, we studied
      the extent of increase in waist circumference by infusing dialysate. METHODS: The
      abdominal circumference of 44 PD patients was measured before and after infusion
      of dialysate. The change in circumference was compared to body mass index (BMI)
      and length of the abdominal cavity, defined by the distance between the processus
      xiphoideus and the os pubis. RESULTS: Mean abdominal circumferences at the
      umbilicus and the iliac crest increased from 92.6 +/- 10.1 to 95.5 +/- 10.0 cm
      and from 95.2 +/- 8.5 to 96.2 +/- 6.3 cm, respectively, when dialysate was
      infused (p value for both < 0.01). A dialysate volume of 2000 mL increased the
      circumference only slightly more than the increase seen with 1500 mL. The change
      in circumference was not correlated with the circumference before the infusion,
      BMI, height of the patient, or length of the abdominal cavity. CONCLUSIONS: This
      study shows that normal PD fill volumes increase the waist circumference only a
      little. This finding should ease the patient's presumption of PD changing the
      body image.

PMID- 20150584
TI  - Refractory ascites due to portal hypertension in autosomal dominant polycystic
      kidney disease (ADPKD) patients successfully treated with peritoneal dialysis.
AB  - Refractory ascites is uncommon in autosomal dominant polycystic kidney disease
      (ADPKD) but it usually makes the patient physically and psychologically
      handicapped. Two uremic ADPKD patients in our hospital developed refractory
      ascites after 1 year on hemodialysis. The refractory ascites was due to portal
      hypertension, which was caused primarily by portal outflow obstruction due to the
      numerous enlarged cysts in the liver and secondarily by increased portal inflow.
      We attempted continuous ambulatory peritoneal dialysis (CAPD) to treat the 2
      patients and obtained satisfactory results. Not only was the refractory ascites
      well controlled, but also the portal hypertension disappeared. Based on our
      experience, we think CAPD could serve as a very effective therapy to treat the
      refractory ascites of portal hypertension due to polycystic liver in uremic ADPKD
      patients.

PMID- 20150585
TI  - Peritoneal inflammation after twenty-week exposure to dialysis solution: effect
      of solution versus catheter-foreign body reaction.
AB  - BACKGROUND: We hypothesized that both sterile solutions and foreign body reaction
      to the peritoneal dialysis catheter are associated with inflammatory changes in
      rats exposed to hypertonic solution. METHODS: Four hypertonic solutions (30 - 40
      mL) were injected daily via needle and syringe over 20 weeks in 4 groups of rats:
      4.25% standard clinical solution (LAC), LAC plus pyridoxamine (PYR), LAC plus
      ethyl pyruvate (EP), and a biocompatible 4% dextrose solution (BIC). Two groups
      received catheters: a non-injected 4-week catheter group (C4) and a group
      injected for 20 weeks with the BIC solution (CI). Control animals (CON) were not
      injected. In the C4 group, adherent cells were separated from the catheter and
      examined by culture and electron microscopy to ensure that animals were bacteria
      free prior to exposure to solution. Animals underwent transport experiments to
      determine mass transfer coefficients of mannitol (MTC(M)) and albumin (MTC(A)),
      osmotic filtration flux (J(osm)), and hydrostatic pressure-driven flux (J(p)).
      After euthanasia, tissues were examined for submesothelial thickness, vascular
      density, and immunohistochemistry for various cytokines. RESULTS: The catheter
      cell layer was free of bacteria and consisted of macrophages, lymphocytes,
      mesothelial cells, and fibroblastic cells. Marked differences in angiogenesis and
      submesothelial thickening were noted for the catheter groups. Transport
      differences were mixed: MTC(M) was significantly less for the CI group and MTC(A)
      was variable among the groups. There were no differences among groups for J(osm)
      or J(p). Inflammatory markers in the catheter-adherent cells correlated with
      inflammatory changes in the tissue. These data demonstrate significant changes in
      submesothelial thickness, angiogenesis, transport function, and inflammatory
      markers between animals injected with sterile solutions over 20 weeks with and
      without catheters. CONCLUSION: An indwelling catheter amplifies peritoneal
      inflammation from dialysis solutions through a foreign body reaction. Our data
      also suggest that additives to existing solutions may have limited the effect on
      inflammatory response to non-biocompatible solutions.

PMID- 20150586
TI  - Metabolic effects of incremental doses of intraperitoneal amino acids on
      automated peritoneal dialysis.
AB  - BACKGROUND: The use of amino acid (AA) dialysate to ameliorate protein-energy
      malnutrition has been limited by adverse metabolic effects. OBJECTIVE: We
      undertook this study to examine the acute metabolic effects of escalating doses
      of AAs delivered with lactate/bicarbonate dialysate on automated peritoneal
      dialysis (APD). PATIENTS AND METHODS: 12 APD patients were treated with
      conventional lactate-buffered dialysate (week 1), followed by lactate/bicarbonate
      buffered dialysate (week 2), then 2 - 2.5 L 1.1% AA solution were added (week 3),
      and then an additional 2 - 2.5 L 1.1% AA were added (week 4). The primary
      outcomes were change in serum bicarbonate and pH, change in protein catabolic
      rate (PCR), and change in normalized ultrafiltration (milliliters/gram of
      carbohydrate infused). RESULTS: Serum bicarbonate rose from week 1 to week 2
      (28.9 +/- 3.2 vs 26.9 +/- 4.1 mmol/L, p = 0.03). Addition of one bag of AAs led
      to a decline in plasma bicarbonate (26.9 +/- 2.1 vs 28.9 +/- 3.2 mmol/L, p <
      0.01), which was further magnified by the addition of the second bag of AAs (23.8
      +/- 2.7 vs 26.9 +/- 2.1 mmol/L, p < 0.01). Serum bicarbonate fell significantly
      by week 4 compared to week 1 (23.8 +/- 2.7 vs 26.9 +/- 3.2 mmol/L, p < 0.01)
      although there was no significant change in venous pH or PCR when week 4 was
      compared to week 1. Normalized ultrafiltration was stable for the first 3 weeks
      but rose significantly in week 4 compared to week 1 (5.32 +/- 2.30 vs 4.14 +/-
      1.58 mL/g, p = 0.03). CONCLUSIONS: Higher doses of AAs mixed with newer
      bicarbonate/lactate dialysate on APD result in a small decrease in serum
      bicarbonate but improved normalized ultrafiltration. This merits further study as
      both a nutritional supplement and a glucose-sparing strategy.

PMID- 20150587
TI  - Discovery of antagonists for human scavenger receptor CD36 via an ELISA-like high
      throughput screening assay.
AB  - CD36, a member of the class B scavenger receptor, is a high-affinity receptor for
      oxidatively modified low-density lipoprotein (oxLDL). Extensive evidence points
      to a significant role of CD36 in atherosclerosis and suggests that CD36 could be
      a potential target for treatment of atherosclerosis. Here, the extracellular
      domain of human CD36 (Gly(30)-Asn(439)) was expressed in Escherichia coli as
      His(6)-tagged soluble CD36 (sCD36), which could bind oxLDL specifically and
      effectively inhibit the uptake of oxLDL by murine macrophage RAW 264.7 cells. An
      enzyme-linked immunosorbent assay (ELISA)-like high-throughput screening (HTS)
      assay was developed for the discovery of CD36 antagonists, based on the
      competition of sCD36 binding to immobilized oxLDL and detection with a monoclonal
      antibody against His-tag. This assay was suitable for HTS in a 96-well format and
      was robust and reliable according to the evaluation parameter Z' value of 0.82.
      The developed HTS assay was applied to both pure chemical compounds and microbial
      secondary metabolite crude extracts to identify CD36 antagonists. Three active
      compounds-sodium danshensu (DSS), rosmarinic acid (RA), and salvianolic acid B
      (SAB)-were shown to be antagonistic to sCD36-oxLDL binding and further validated
      by their inhibition of oxLDL uptake in RAW 264.7 cells. These results suggest
      that the ELISA-like assay represents a promising screening for identifying
      bioactive molecules targeting atherosclerosis at the level of CD36-ligand
      binding.

PMID- 20150588
TI  - Screening and identification of recombinant anti-idiotype antibodies against
      gastric cancer and colon cancer monoclonal antibodies by a phage-displayed single
      chain variable fragment library.
AB  - Several monoclonal antibodies (McAbs) have been developed that show high
      sensitivity and specificity to gastric cancer and colorectal cancer. However, few
      of the antigens recognized by these antibodies have been identified. The authors
      now report the selection of anti-idiotype (anti-id) antibodies of MGb1 McAb
      against gastric cancer and MC5 McAb against colorectal cancer using phage
      displayed single-chain variable fragment (ScFv) libraries. After purification,
      the anti-id antibodies were approximately 30 kd and could be recognized by
      MGb1/MC5 McAb. Anti-id antibodies significantly blocked the binding of MGb1 and
      MC5 to gastric cancer/colorectal cancer cells, respectively, suggesting that the
      antibodies were specific to MGb1 and MC5. Antibodies against gastric and
      colorectal cancer could be detected in mice at 6 weeks after immunization with
      the anti-id antibodies. At week 8, antibody titers reached 1:400. The anti-id
      antibodies may be useful as novel reagents for developing vaccines against
      gastric cancer and colorectal cancer.

PMID- 20150589
TI  - Multidrug resistance reversal agent, NSC77037, identified with a cell-based
      screening assay.
AB  - The development of multidrug resistance (MDR) remains a significant obstacle in
      treating cancer patients with chemotherapy. To identify small-molecule compounds
      that can reverse MDR, the authors used a cell-based screening assay with an MDR
      ovarian cancer cell line. Incubating MDR cells with a sublethal concentration of
      paclitaxel in combination with each of 2000 small-molecule compounds from the
      National Cancer Institute Diversity Set Library, they identified NSC77037. The
      cytotoxic activity of NSC77037 and the duration of its effect were evaluated in
      vitro using a panel of cancer cell lines expressing permeability glycoprotein
      (Pgp), multiple drug resistance protein 1 (MRP 1), and breast cancer resistance
      protein (BCRP). The mechanism of its effects was further analyzed by assessing
      the retention of calcein and Pgp-ATPase activity. The relative potency of MDR
      reversal by NSC77037 was significantly higher than that of frequently used MDR
      reversal agents such as verapamil and cyclosporine A. NSC77037 reversed Pgp
      without reversing MRP or BCRP-mediated MDR. NSC77037, at a concentration of >10
      microM, moderately inhibited the proliferation of both sensitive and resistant
      cell lines, but the inhibitory effect of NSC77037 was not altered by coincubation
      with the Pgp inhibitor verapamil, suggesting that NSC77037 itself is not a
      substrate of Pgp. NSC77037 directly inhibited the function of Pgp in a dose
      dependent manner, but it did not alter the protein expression level of Pgp. The
      use of NSC77037 to restore sensitivity to chemotherapy or to prevent resistance
      could be a potential treatment strategy for cancer patients.

PMID- 20150590
TI  - A novel bioassay for detecting GPCR heterodimerization: transactivation of beta 2
      adrenergic receptor by bradykinin receptor.
AB  - Many G-protein-coupled receptors (GPCRs) have been shown to form heteromeric
      complexes primarily by biochemical methods, including competitive radioligand
      binding assays or measurements of changes in second-messenger concentration in
      lysed cells. These results are often cell line specific, and the expression of
      other cell surface proteins makes it difficult to detect potential functional
      consequences of GPCR interaction. Here, 2-electrode voltage clamping in Xenopus
      oocytes was used as a bioassay to explore heterodimerization of bradykinin type 2
      receptor (Bk2R) and beta 2 adrenergic receptor (beta(2)AR), using chloride
      channels as outputs for receptor activation. The data show for the first time
      that these 2 receptors heterodimerize with functional consequences. Stimulation
      with bradykinin induced activation of Galphaq- and transactivation of Galphas
      coupled pathways in oocytes expressing Bk2R and beta(2)AR. To corroborate these
      data, potential receptor interaction was examined in PC12 cells, a cell line that
      endogenously expresses both receptors, and confirmed that stimulation with
      bradykinin transactivates beta(2)AR. In both oocytes and PC12 cells,
      transactivation was ablated by Bk2R or beta(2)AR inverse agonists, suggesting
      that transactivation occurred directly through both receptors. This is the first
      evidence of Bk2R/beta(2)AR physical interaction, forming a functional
      heterodimer. The oocyte system may prove highly useful for exploration of GPCR
      heterodimerization and the functional consequences thereof.

PMID- 20150591
TI  - Assessing the stability of membrane proteins to detect ligand binding using
      differential static light scattering.
AB  - Protein stabilization upon ligand binding has frequently been used to identify
      ligands for soluble proteins. Methods such as differential scanning fluorimetry
      (DSF) and differential static light scattering (DSLS) have been employed in the
      384-well format and have been useful in identifying ligands that promote
      crystallization and 3D structure determination of proteins. However, finding a
      generic method that is applicable to membrane proteins has been a challenge as
      the high hydrophobicity of membrane proteins and the presence of detergents
      essential for their solubilization interfere with fluorescence-based detections.
      Here the authors used MsbA (an adenosine triphosphate binding cassette
      transporter), CorA (a Mg(++) channel), and CpxA (a histidine kinase) as model
      proteins and show that DSLS is not sensitive to the presence of detergents or
      protein hydrophobicity and can be used to monitor thermodenaturation of membrane
      proteins, assess their stability, and detect ligand binding in a 384-well format.

PMID- 20150592
TI  - A dual estrogen receptor TR-FRET assay for simultaneous measurement of steroid
      site binding and coactivator recruitment.
AB  - The human estrogen receptors (hER) are members of the nuclear hormone receptor
      (NHR) superfamily and represent important drug targets for the pharmaceutical
      industry. Initially, ligand binding assays were used to identify novel ligands
      using receptors purified from native tissues. With the advent of molecular
      cloning techniques, cell-based transactivation assays have been the gold standard
      for many years of drug discovery. With the elucidation of the structural
      mechanisms underlying the activation of NHRs, cell-free assays with purified
      receptors have become important tools to directly assess different binding sites
      (e.g., the hormone binding site or the cofactor binding site). The available cell
      free assays have so far facilitated the study of one binding site at a time. With
      the introduction of Terbium (Tb(3+))-based time-resolved fluorescence energy
      transfer (TR-FRET), it has become possible to measure 2 different interactions
      within 1 test tube in parallel. The authors have applied this technology to
      develop a dual readout system for the simultaneous monitoring of steroid hormone
      site binding and cofactor peptide recruitment. They took advantage of a
      commercially available fluorescent tracer as an indicator for classical steroid
      site binding and designed a novel peptide derived from the peroxisome
      proliferator-activated receptor gamma coactivator-1a (PGC1a) as an indicator for
      functional agonistic behavior of a test compound. The established assay is able
      to differentiate between agonists, antagonists, partial agonists, and compounds
      binding to the cofactor recruitment site. The IC(50) values obtained for a number
      of reference compounds in the multiplexed assay are in concordance with published
      data. The simple 1-step mix-and-measure protocol gives excellent quality and
      robustness and can be miniaturized to 5-microL volume.

PMID- 20150593
TI  - Stanley Wallach, a personal tribute and thank you.

PMID- 20150594
TI  - Tribute to Dr. Stanley Wallach and Pearl Small.

PMID- 20150595
TI  - Comparative effectiveness research (CER): opportunities and challenges for the
      nutritional industry.

PMID- 20150596
TI  - The risks of copper toxicity contributing to cognitive decline in the aging
      population and to Alzheimer's disease.
AB  - It is a pleasure and an honor to contribute a paper to a special issue of the
      Journal of the American College of Nutrition honoring Stanley Wallach and Pearl
      Small. In this brief review I advance the hypothesis that copper toxicity is the
      major cause of the epidemic of mild cognitive impairment and Alzheimer's disease
      engulfing our aging population. This epidemic is recent, exploding in the last 50
      60 years. The disease was virtually unknown 100 years ago. And it involves only
      developed countries that use copper plumbing. Something in our environment
      associated with development is poisoning the minds of our aged. The epidemic is
      associated with the use of copper plumbing, and the taking of copper in multi
      mineral supplements. Food copper (organic copper) is processed by the liver and
      is transported and sequestered in a safe manner. Inorganic copper, such as that
      in drinking water and copper supplements, largely bypasses the liver and enters
      the free copper pool of the blood directly. This copper is potentially toxic
      because it may penetrate the blood/brain barrier. I review a web of animal and
      human data that tightens the noose around the hypothesis that copper toxicity is
      causing the epidemic of Alzeimer's disease and loss of cognition in our aging
      population.

PMID- 20150597
TI  - History of parenteral nutrition.
AB  - The concept of feeding patients entirely parenterally by injecting nutrient
      substances or fluids intravenously was advocated and attempted long before the
      successful practical development of total parenteral nutrition (TPN) four decades
      ago. Realization of this 400 year old seemingly fanciful dream initially required
      centuries of fundamental investigation coupled with basic technological advances
      and judicious clinical applications. Most clinicians in the 1950's were aware of
      the negative impact of starvation on morbidity, mortality, and outcomes, but only
      few understood the necessity for providing adequate nutritional support to
      malnourished patients if optimal clinical results were to be achieved. The
      prevailing dogma in the 1960's was that, "Feeding entirely by vein is impossible;
      even if it were possible, it would be impractical; and even if it were practical,
      it would be unaffordable." Major challenges to the development of TPN included:
      (1) formulate complete parenteral nutrient solutions (did not exist), (2)
      concentrate substrate components to 5-6 times isotonicity without precipitation
      (not easily done), (3) demonstrate utility and safety of long-term central venous
      catheterization (not looked upon with favor by the medical hierarchy), (4)
      demonstrate efficacy and safety of long-term infusion of hypertonic nutrient
      solutions (contrary to clinical practices at the time), (5) maintain asepsis and
      antisepsis throughout solution preparation and delivery (required a major culture
      change), and (6) anticipate, avoid, and correct metabolic imbalances or
      derangements (a monumental challenge and undertaking). This presentation recounts
      approaches to, and solution of, some of the daunting problems as really occurred
      in a comprehensive, concise and candid history of parenteral nutrition.

PMID- 20150598
TI  - Vitamin D3 distribution and status in the body.
AB  - OBJECTIVE: To estimate the amount, type, and tissue distribution of vitamin D in
      the adult body under typical inputs. METHODS: Review and reanalysis of published
      measurements and analysis of tissue samples from growing pigs raised in
      confinement on diets providing about 2000 IU vitamin D/day. Cholecalciferol and
      25-hydroxyvitamin D [25(OH)D] concentration measured by HPLC. RESULTS: Mean serum
      25(OH)D in all studies combined was 45 nmol/L. At the level of vitamin D
      repletion represented by this concentration, total body vitamin D would be 14,665
      IU for a 70 kg adult woman. 65% of this total was present as native
      cholecalciferol and 35% as 25(OH)D. Nearly three-quarters of the cholecalciferol
      was in fat, while 25(OH)D was more evenly distributed throughout the body (20% in
      muscle, 30% in serum, 35% in fat, and 15% in all other tissues). At the daily
      vitamin D consumption rates in these animals total body stores provided only a
      approximately 7-day reserve. CONCLUSIONS: At total intakes on the order of 2000
      IU/day, an adult has very little vitamin D reserve, despite intakes 10x the
      current recommendations. Those recommended inputs need to be increased by at
      least an order of magnitude. Food tables that fail to take into account 25(OH)D
      content of various meat products lead to underestimation of dietary vitamin D
      intake.

PMID- 20150599
TI  - Impact of the discovery of human zinc deficiency on health.
AB  - The essentiality of zinc was recognized 46 years ago. Zinc deficiency resulting
      in growth retardation, hypogonadism, immune dysfunction and cognitive impairment
      affects nearly 2 billion subjects in the developing world. High phytate content
      of the cereal proteins consumed in the developing world, results in decreased
      availability of zinc for absorption. Zinc therapy has been very successful and
      life saving measure in patients with acrodermatitis enteropathica and Wilson's
      disease. Beneficial therapeutic responses of zinc supplementation have been
      ovserved in acute diarrhea in children, chronic hepatitis C, shigellosis,
      leprosy, leishmaniasis, and common cold. Zinc supplementation was effective in
      decreasing incidences of infection in elderly and patients with sickle cell
      disease. Zinc supplementation was effective in preventing blindness in 25% of the
      elderly with dry type of age related macular degeneration. Zinc supplementation
      in the elderly decreased oxidative stress and decreased generation of
      inflammatory cytokines. Zinc is an intracellular signaling molecule in monocytes,
      dendritic cells and macrophages and it plays an important role in cell-mediated
      immune functions and oxidative stress. Zinc is also an anti-inflammatory agent.
      These unique properties of zinc may have significant therapeutic benefits in
      several diseases in humans. In many diseases concurrent zinc deficiency may
      complicate the clinical features, affect adversely immunological status, increase
      oxidative stress and increase generation of inflammatory cytokines. Oxidative
      stress and chronic inflammation may play important causative roles in many
      chronic diseases, including atherosclerosis, several malignancies, neurological
      disorders, and auto-immune diseases. It is therefore, important that status of
      zinc is assessed and zinc deficiency corrected in these chronic diseases. A
      controlled clinical trial of zinc supplementation in these disorders in order to
      document the preventive and therapeutic effects of zinc is warranted.

PMID- 20150600
TI  - Bean amylase inhibitor and other carbohydrate absorption blockers: effects on
      diabesity and general health.
AB  - Many believe that excessive intake of refined carbohydrates (CHO) plays a major
      role in the development of obesity/overweight, type 2 diabetes mellitus and
      insulin resistance, a collection of events commonly referred to as "diabesity,"
      and have sought natural means to overcome these linked perturbations. As a first
      approach, planned diets with low portions of refined CHO have become popular.
      However, these diets do not satisfy everyone; and many are concerned over
      replacing CHO with more fats. As a second option, addition of soluble fiber to
      the diet can slow absorption of refined CHO, i.e., lower the glycemic index of
      foods and overcome or at least ameliorate many of the adverse reactions resulting
      from increased refined CHO ingestion. Unfortunately, the general public does not
      favor diets high in fiber content, and various fibers can lead to
      gastrointestinal problems such as gas and diarrhea. A third choice to favorably
      influence CHO absorption is to use natural dietary supplements that block or slow
      CHO absorption in the gastrointestinal tract via inhibiting enzymes necessary for
      CHO absorption -amylase and alpha-glucosidases. Although a number of natural
      supplements with anti-amylase activity have been recognized, the most studied and
      favored one is white kidney bean extract. Animal and human studies clearly show
      that this agent works in vivo and has clinical utility. This paper reviews many
      aspects of diabesity and the use of "carb blockers" to prevent and ameliorate the
      situation. In many respects, carb blockers mimic the beneficial effects of
      fibers.

PMID- 20150601
TI  - Effect of exclusion diet with nutraceutical therapy in juvenile Crohn's disease.
AB  - BACKGROUND: Most moderate-severe juvenile Crohn's disease (CD) patients are in a
      constant catabolic state resulting in poor weight gain and growth failure. Anti
      inflammatory, immunomodulatory, and monoclonal antibody drugs, as well as growth
      hormone (GH), frequently fail to achieve sustained remission or reverse growth
      failure. OBJECTIVE: To test whether an exclusion diet with nutraceutical therapy
      (DNT) could induce sustained clinical remission and weight gain, and if so does
      this enhance the ability for GH to reverse growth failure. METHODS: An
      uncontrolled prospective case study was undertaken in six moderate- severe CD
      patients, two of whom had completed growth. All were treated with DNT. Adequate
      caloric and protein ( >or= 3g/kg/d) intake for catch up weight was prescribed.
      Dairy products, certain grains and carrageenan containing foods were eliminated.
      Nutraceuticals, consisting of fish peptides, bovine colostrum, boswellia serrata,
      curcumin and a multivitamin were administered daily. Lactobacillus GG, a
      probiotic, was administered twice weekly. Recombinant human GH (rhGH) was
      administered daily. RESULTS: Within 2 months of starting DNT all six patients
      went into remission, with discontinuation of all pharmacological drugs. Three
      patients have remained in sustained remission for 4 to 8 years. One patient with
      very severe CD had recurrence of CD symptoms after being in complete remission
      for 18 months, one patient was in remission for 3 years but symptoms recurred
      when she became less compliant to DNT and one recently treated patient remains in
      remission after 6 months. With the addition of rhGH, the 4 growing patients had
      good-excellent growth response CONCLUSION: DNT engendered prolonged remission and
      restoration of normal weight in moderate-severe juvenile CD patients, providing
      conditions that enabled rhGH to stimulate growth. These findings justify larger
      controlled trials to evaluate the long-term benefit of compliance to DNT in both
      juvenile and adult CD patients.

PMID- 20150603
TI  - Lost in translation: reviewing the role of the discharge liaison nurse in Wales.
AB  - In Wales, the National Leadership and Innovation Agency in Healthcare (NLIAH)
      Change Agent Team (CAT) has found that its service improvement methodology of
      Communities of Practice (CoP), where motivated frontline staff in health and
      social care come together to share issues and develop solutions to mutual
      problems, is a highly effective and informative tool. Health and social care
      organizations in Wales are in the process of working to develop processes and
      solutions to remedy the challenges they have over patients with long lengths of
      stay. This article shows how by speaking to the frontline staff, whose role it is
      to help people whose discharge is likely to be complex or problematic, they often
      have most insight into the solutions required to alleviate the situation. The
      learning in this article is that there is no one solution to improve the
      discharge process; however there are a number of small changes and improvements
      required, which if done consistently can have a significant impact. The findings
      here have been shared with Welsh government policy leads and health and social
      care executive teams to inform their planning and actions on how to resolve the
      challenge of reducing length of stay.

PMID- 20150602
TI  - The degree of saturation of fatty acids in dietary fats does not affect the
      metabolic response to ingested carbohydrate.
AB  - BACKGROUND: We are interested in the metabolic response to ingested
      macronutrients, and the interaction between macronutrients in meals. Previously,
      we and others reported that the postprandial rise in serum glucose following
      ingestion of 50 g carbohydrate, consumed as potato, was markedly attenuated when
      butter was ingested with the carbohydrate, whereas the serum insulin response was
      little affected by the combination. OBJECTIVE: To determine whether a similar
      response would be observed with three other dietary fats considerably different
      in fatty acid composition. DESIGN: Nine healthy subjects received lard, twelve
      received olive oil and eleven received safflower oil as a test meal. The subjects
      ingested meals of 25 g fat (lard, olive oil or safflower oil), 50 g CHO (potato),
      25 g fat with 50 g CHO or water only. Glucose, C peptide, insulin,
      triacylglycerols and nonesterified fatty acids were determined. RESULTS:
      Ingestion of lard, olive oil or safflower oil with potato did not affect the
      quantitative glucose and insulin responses to potato alone. However, the
      responses were delayed, diminished and prolonged. All three fats when ingested
      alone modestly increased the insulin concentration when compared to ingestion of
      water alone. When either lard, olive oil or safflower oil was ingested with the
      potato, there was an accelerated rise in triacylglycerols. This was most dramatic
      with safflower oil. CONCLUSIONS: Our data indicate that the glucose and insulin
      response to butter is unique when compared with the three other fat sources
      varying in their fatty acid composition.

PMID- 20150604
TI  - The use of patient complaints to drive quality improvement: an exploratory study
      in Taiwan.
AB  - This study aims to investigate the nature and resolutions of patient complaints
      and further to explore the use of complaints to drive quality improvement in a
      selected hospital in Taiwan. A teaching hospital (i.e. the Case Hospital) in
      Taiwan was purposefully chosen for a case study. The author conducted the
      critical incident technique (CIT) using questionnaires to obtain information
      about the complaints and the process of their resolutions. To enhance the
      reliability of the study, the author also conducted non-participant observations
      as an outsider at the Case Hospital. In this study, 59 complainants registered 87
      complaints. The CIT found that care/treatment, humaneness and communication were
      the most common causes of complaints. The response time of patient complaints
      averaged 1.76 days, except for five cases in which response time was not
      reported. The majority of complaints were resolved within three days. Moreover,
      this study found that of 149 resolutions, 105 taken by the hospital involved an
      explanation of the facts to complainants (n = 41), investigation of events (n =
      33) and empathy with complainants (n = 31). The lack of any systematic use of
      complaints data was one of the most crucial failures of the Case Hospital.
      Instead of attempting to use such data as the basis for initiating quality
      improvement measures, complaints were consigned to a 'black hole' where their
      existence was conveniently forgotten. Based on this study, the author suggests
      ways to strengthen the capacity of the hospital in terms of using patient
      feedback and complaints to improve the quality.

PMID- 20150605
TI  - Patient satisfaction with primary care in Armenia: good rating of bad services?
AB  - The study assessed the level of patient satisfaction at selected primary health
      care facilities in Lori and Shirak provinces of Armenia. Self-administered
      questionnaires were distributed to 684 recent clients at primary health-care
      facilities. The majority of patients were satisfied with their provider (mean
      satisfaction score of 1.75 out of maximum 2). Most patients (89.0%) would visit
      the same provider again, and would recommend the provider to friends (85.6%).
      Satisfaction with other aspects of care, including waiting time, accessibility of
      services, confidentiality and cleanliness of the facility, was also high (mean
      score of 1.70 out of 2). Seventy-eight percent of respondents considered the care
      they received to be 'excellent' or 'good'. The less educated and those in rural
      areas were more likely to be satisfied with the provider's quality. Despite the
      fundamental problems now challenging the Armenian primary health-care sector,
      patient satisfaction remains high. Given the high level of reported satisfaction,
      more focused satisfaction research tools and alternative approaches to patient
      assessments of care are needed to inform quality improvement in the Armenian
      setting.

PMID- 20150606
TI  - One question, two answers: do the two most commonly used methods of sampling
      describe the length of the prospective wait for admission to hospital?
AB  - To demonstrate that the incomplete waits captured at the time and by means of a
      census may not have the same distribution as the completed waits captured as a
      result of admission during a specified calendar period, cataracts added to
      waiting lists in England, Scotland, Wales and Northern Ireland between 1 July
      2003 and 31 December 2005, and admitted no more than two years after the date of
      their enrolment, were identified using Hospital Episode Statistics, Scottish
      Morbidity Records, the Admitted Patient Care database and the Hospital Inpatient
      System. Census- and event-based sampling produced two sets of records for each
      closed population in which the eventual outcome, and rules about suspension and
      deferral, were the same. The census-based sample (30 September 2005) yielded a
      smaller percentage of waits with a length of one or more days, and the same was
      true for every other length up to the maximum of the event-based sample, e.g. up
      to 728 days (1 July-30 September 2005) and up to 723 days (1 October-31 December
      2005) in Hospital Episode Statistics. The two methods of sampling did not yield
      the same distribution: one might capture the wait in prospect for those newly
      added to the list, but the other does not.

PMID- 20150607
TI  - Major incident planning in primary care trusts in north-west England: a cross
      sectional survey.
AB  - The Civil Contingencies Act (2004) requires UK primary care trusts (PCTs) to plan
      and respond to major health incidents. We carried out a cross-sectional survey of
      all PCTs in the north-west region of England using a telephone interview with a
      structured questionnaire. We assessed: (1) staff members responsible for
      emergency planning; (2) risk assessment; (3) training and exercises; and (4) the
      planned response to a major incident. Response rate was 61% (20/33). Twelve out
      of 20 employed an emergency planning officer. All responding PCTs had
      participated in a tabletop exercise in the previous year and nine of 20 in a live
      exercise in the previous three years. Nine provided major incident training to
      new staff. Fifteen had discussed major incident preparations with their local
      acute trust but none could quantify the support they would be able to provide in
      terms of accelerated discharges. We have revealed potentially serious
      deficiencies in the emergency preparedness of many PCTs. PCTs are expected to
      play a vital role in coordinating the National Health Service (NHS) response to a
      major incident and these results have important implications for the ability of
      the NHS as a whole to effective respond to such incidents.

PMID- 20150608
TI  - The skills gap in hospital management: a comparative analysis of hospital
      managers in the public and private sectors in South Africa.
AB  - A lack of management capacity has been identified as the key stumbling block to
      attaining the goals of health for all in South Africa. As part of the overall
      management development process, this research aims to identify the skills that
      are important for health services management and to evaluate managers' self
      assessed proficiency in each of these skills. We also examined the impact of past
      training on perceived competency levels. A cross-sectional survey using a self
      administered questionnaire was conducted among 404 hospital managers in the South
      African public and private sectors. Respondents were asked to rate the level of
      importance that each proposed competency had in their job and to indicate their
      proficiency in each skill. Both public and private sector managers rated
      competencies related to 'people management', 'self-management' and 'task-related
      skills' highest followed by 'strategic planning' and 'health delivery',
      respectively. The largest differences between mean importance rating and mean
      skill rating for public sector managers were for people management skills, task
      related skills and self-management skills. The largest deficits for private
      sector managers were for people management skills, self-management skills and
      health delivery skills. Informal management development programmes were found to
      be more valuable in improving management skills. These findings reflect the
      reality of the local health service environment and the need of health managers.
      It will be useful in the conceptualization, design and delivery of health
      management programmes aimed at enhancing current and future management and
      leadership capacity in the health sector in South Africa.

PMID- 20150609
TI  - Reducing the rate of unregistered studies.
AB  - The aim of this audit cycle is to measure the extent to which unregistered or
      wrongly classified studies (research, clinical audit, satisfaction
      surveys/service evaluations) are conducted within a National Health Service (NHS)
      Trust, and to ascertain whether promotion of the correct processes can improve
      the results. An anonymous questionnaire was sent to staff in a single NHS Trust
      via internal post and email concerning unregistered or wrongly classified studies
      being conducted. An information sheet was attached to the questionnaire, which
      gave a brief description and information relating to conducting different types
      of study. The audit was conducted before and after the introduction of a variety
      of promotional activities within the Research and Development (R&D) department.
      The percentage of unregistered research was shown to be 45.8% in audit 1, with
      audit 2 showing a reduction in unregistered studies to 5.2% (P = 0.005). For
      clinical audits the results were similar between audits (with no additional
      promotion) (2.3-2.4%). Satisfaction surveys which were included in the promotion
      of the research department reduced its level of unregistered studies from 46% to
      5% (P = 0.0084). With the targeted and persistent promotion of the relevant
      departments a dramatic reduction in unregistered studies can be achieved (P =
      0.01).

PMID- 20150610
TI  - Data mining for health executive decision support: an imperative with a daunting
      future!
AB  - Data mining is highly profiled. It has the potential to enhance executive
      information systems. Such enhancement would mean better decision-making by
      management, which in turn would mean better services for customers. While the
      future of data mining as technology should be exciting, some are worried about
      privacy concerns, which make the future of data mining daunting. This paper
      examines why data mining is highly profiled - the imperative toward data mining,
      data mining models and processes. Additionally, the paper examines some of the
      benefits and challenges of using data mining processes within the health-care
      arena. We cast the future of data mining by highlighting two of the many data
      mining tools available - one commercial and one freely available. Subsequently,
      we discuss a number of social and technical factors that may thwart the extensive
      deployment of data mining, especially when the intent is to know more about the
      people that organizations have to serve and cast a view of what the future holds
      for data mining. This component is especially important when attempting to
      determine the longevity of data mining within health-care organizations. It is
      hoped that our discussions would be useful to organizations as they engage data
      mining, strategies for executive information systems and information policy
      issues.

PMID- 20150611
TI  - Alcohol consumption, obesity, estrogen treatment and breast cancer.
AB  - Alcohol consumption increases breast cancer risk in postmenopausal women in a
      dose-dependent manner. The objective of the present study was to determine if the
      effect of alcohol on mammary cancer is modified by body weight and exogenous
      estrogen. Ovariectomized mice of various body weights, receiving estrogen or
      placebo supplementation, and consuming water or alcohol were injected with
      mammary cancer cells. Alcohol intake resulted in insulin sensitivity and
      increased tumor growth in obese mice. Exogenous estrogen alone inhibited tumor
      growth. The combination of estrogen and alcohol overcame the inhibitory effects
      of estrogen on tumor growth in obese mice. Alcohol consumption increased the
      circulating estrogen and leptin levels. In conclusion, alcohol and estrogen
      treatment can modify mammary tumor growth, possibly through the regulation of
      estrogen and leptin, especially in obese mice.

PMID- 20150612
TI  - Direct effects of delta opioid receptor agonists on invasion-associated
      activities of HCT-8/E11 colon cancer cells.
AB  - BACKGROUND: Opioids and opioid receptors are an integral part of the tumour
      microenvironment and hence may influence tumour progression. Studies on direct
      effects of opioids on invasion-associated cellular activities are equivocal. We
      wanted to clarify these differences. MATERIALS AND METHODS: The direct effects of
      the delta opioid receptor (DOR) agonists [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE),
      leu-enkephalin and [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) on invasion-associated
      activities of HCT-8 myc-DOR and HCT-8 FLAG-DOR colon cancer cells stably
      overexpressing DOR were studied. RESULTS: The opioids showed a trend to stimulate
      invasion of single cells in collagen in one clone, while they did not influence
      invasion of the other clone. In other invasion assays, no effects were observed.
      They did not affect cell growth and homotypical cell-cell adhesion. DPDPE at 0.1
      muM inhibited directional migration; the other opioids and concentrations tested
      were inefficient. CONCLUSION: Opioids differently influence invasion-associated
      cellular activities, depending on the expression level of DOR, experimental set
      up, type and concentration of opioid.

PMID- 20150613
TI  - Evaluation of [99mTc-(CO)3-X-Y-Bombesin(7-14)NH2] conjugates for targeting
      gastrin-releasing peptide receptors overexpressed on breast carcinoma.
AB  - BACKGROUND: Gastrin-releasing peptide (GRP) receptors are overexpressed on a
      variety of human carcinomas, including those of the breast. These receptors may
      be targeted with bombesin (BBN), which binds to GRP receptors with high affinity
      and specificity. The aim of this study was to develop a (99m)Tc(I)-BBN analog
      with favorable pharmacokinetic properties in order to improve the visualization
      of breast cancer tissue. MATERIALS AND METHODS: Solid-phase peptide synthesis was
      used to produce a series of X-Y-BBN-NH2 conjugates, where X is pyrazolyl (PZ1) or
      2,3-diaminopropionic acid (DPR) and Y is a spacer sequence. Their metallated
      counterparts were prepared by reacting [(99m)Tc-(H(2)O)(3)(CO)(3)](+) with the
      corresponding ligand. RESULTS: While the PZ1 conjugates exhibited higher GRP
      receptor binding affinities in vitro, the DPR analogs demonstrated superior
      target tissue accumulation and pharmacokinetic properties in vivo. CONCLUSION:
      These results demonstrate the ability of the DPR derivatives
      (Y=glycylserylglycine, triserine) to clearly identify the T47-D tumor tissue in
      xenografted SCID mice.

PMID- 20150614
TI  - Disulfide-linked liposomes: effective delivery vehicle for Bcl-2 antisense
      oligodeoxyribonucleotide G3139.
AB  - BACKGROUND: Disulfide-linked oligodeoxyribonucleotide (ODN) liposomes were
      formulated and evaluated for the delivery of antisense ODN G3139 in KB human oral
      carcinoma cells. MATERIALS AND METHODS: Liposomes composed of 1,2-di-(9Z
      octadecenoyl)-3-trimethylammo-nium-propane (DOTAP)/egg phosphatidylcholine/alpha
      tocopheryl polyethylene glycol 1000 succinate were incorporated with
      hydrophobized disulfide-linked ODN. Disulfide-linked ODN liposomes were
      characterized for their size, ODN intracellular delivery, Bcl-2 mRNA and protein
      expression, growth inhibition, and chemosensitization. RESULTS: Intracellular
      delivery of ODN with disulfide-linked ODN liposomes was more efficient than that
      with non-liposomal hydrophobized disulfide-linked ODN. Treatment of the cells
      with disulfide-linked ODN liposomes resulted in efficient Bcl-2 down-regulation
      greater than that with hydrophobized disulfide-linked ODN and consistent with
      that of cellular growth inhibition and the sensitization to daunorubicin in KB
      cells. Disulfide-linked ODN liposomes exhibited superior colloidal stability
      during 5-week storage. CONCLUSION: Disulfide-linked liposomes are effective
      delivery vehicles for antisense ODN.

PMID- 20150615
TI  - Potent pleiotropic anti-angiogenic effects of TM601, a synthetic chlorotoxin
      peptide.
AB  - Chemically synthesized chlorotoxin (TM601) has been studied as a tumor targeting
      peptide. In this study, the anti-angiogenic properties of TM601 are reported.
      MATERIALS AND METHODS: In vitro and in vivo models of angiogenesis and tumor
      growth were used to characterize the anti-angiogenic effects of TM601. RESULTS:
      TM601 bound to proliferating vascular endothelial cells, decreased human
      umbilical vein endothelial cell (HUVEC) invasion, and reduced secretion of
      bioactive matrix metalloproteinase-2 (MMP-2). Using the chick chorioallantoic
      membrane assay (CAM), TM601 inhibited angiogenesis stimulated by any of eight pro
      angiogenic factors, and when TM601 was co-administered with bevacizumab, the
      combination was significantly more potent than a ten-fold increase in bevacizumab
      dose. TM601 did not alter tumor or vascular endothelial cell growth in vitro, but
      TM601 treatment of tumors grown on the CAM decreased tumor growth and intra
      tumoral hemoglobin levels. Intravenously injected TM601 was also shown to
      significantly decrease new blood vessel growth in mice. CONCLUSION: TM601
      inhibits angiogenesis stimulated by many factors and potentiates the anti
      angiogenic effect of bevacizumab.

PMID- 20150616
TI  - The simian virus 40 large tumor antigen activates cSrc and requires cSrc for full
      neoplastic transformation.
AB  - AIM: To investigate the role of the cellular protooncogene product, cSrc, in
      neoplastic transformation by the large tumor antigen of simian virus 40 (TAg),
      the ability of TAg to increase cSrc activity was examined. MATERIALS AND METHODS:
      cSrc activity was measured in cells expressing wild-type or mutant TAg and
      compared to the parental line. RESULTS: The results indicated that TAg expression
      in mouse 3T3 fibroblasts causes a dramatic increase in cSrc activity, a finding
      which establishes TAg as a cSrc activator. This ability depended upon a TAg,
      intact retinoblastoma-susceptibility gene product (Rb) family-binding site. In
      addition, genetic ablation of pRb in mouse fibroblasts increased cSrc activity,
      suggesting that pRb inactivation by TAg might be responsible for the observed
      cSrc activation. Furthermore, down-regulation or genetic ablation of cSrc alone,
      or together with the Src family members, Yes and Fyn, caused a dramatic reduction
      in the ability of TAg to transform mouse fibroblasts. CONCLUSION: Taken together,
      these findings suggest for the first time that cSrc is part of an important
      pathway emanating from TAg and leading to neoplastic conversion.

PMID- 20150617
TI  - Anticancer activity of novel plant extracts from Trailliaedoxa gracilis (W. W.
      Smith & Forrest) in human carcinoid KRJ-I Cells.
AB  - BACKGROUND: Small intestinal (SI) neuroendocrine tumors (NETs) are rare neoplasms
      derived from neuroendocrine cells presenting distinct clinical symptoms according
      to the ability to secrete neuroamines. Nevertheless, many are asymptomatic and
      misdiagnosed. As response rates to chemotherapy are low, surgery remains the only
      effective treatment. Because many tumors have metastasized at the time of
      diagnosis, curative surgery is rarely achieved. Consequently, a substantial need
      for new therapeutic options has emerged. MATERIALS AND METHODS: The effects of
      novel plant extracts from Trailliaedoxa gracilis (W.W. Smith & Forrest) were
      investigated in the SI-NET cell line KRJ-I and in KRJ-I transplanted mice.
      Proliferation and viability were analyzed using cell counting and WST-1 cell
      proliferation assay. Apoptosis was determined by DAPI staining and electron
      microscopy, and quantified by luminescence assays for caspases 3/7, 6, 8, 9 and
      2. RESULTS: Extracts of Trailliaedoxa gracilis showed a dose-dependent reduction
      of proliferation and induction of apoptosis in the KRJ-I cells. Normal
      fibroblasts were not impaired. Tumor growth inhibition was also observed in
      heterotransplanted SCID (severe combined immunodeficiency) mice. CONCLUSION: The
      in vitro and in vivo outcomes suggest a potential clinical effect of
      Trailliaedoxa gracilis in SI-NETs.

PMID- 20150618
TI  - MicroSPECT/CT imaging and pharmacokinetics of 188Re-(DXR)-liposome in human
      colorectal adenocarcinoma-bearing mice.
AB  - Nanoliposome can be designed as a drug delivery carrier to improve the
      pharmacological and therapeutic properties of drug administration. (188)Re
      labeled nanoliposomes are useful for diagnostic imaging as well as for targeted
      radionuclide therapy. In this study, the in vivo nuclear imaging,
      pharmacokinetics and biodistribution of administered nanoliposomes were
      investigated as drug and radionuclide carriers for targeting solid tumor via
      intravenous (i.v.) administration. The radiotherapeutics ((188)Re-liposome) and
      radiochemotherapeutics ((188)Re-DXR-liposome) were i.v. administered to nude mice
      bearing human HT-29 colorectal adenocarcinoma xenografts. (188)Re-liposome and
      (188)Re-DXR-liposomes show similar biodistribution profile; both have higher
      tumor uptake, higher blood retention time, and lower excretion rate than (188)Re
      N,N-bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA). In contrast to tumor
      uptake, the area under the curve (AUC) value of tumor for (188)Re-liposome and
      (188)Re-DXR-liposome was 16.5- and 11.5-fold higher than that of free (188)Re
      BMEDA, respectively. Additionally, (188)Re-liposome and (188)Re-DXR-liposome had
      a higher tumor-to-muscle ratio at 24 h (14.4+/-2 .7 and 17.14+/-4.1,
      respectively) than (188)Re-BMEDA (1.6+/-0.1). The tumor targeting and
      distribution of (188)Re-(DXR)-liposome (representing (188)Re-DXR-liposome and
      (188)Re-liposome) can also be acquired by signal photon-emission computed
      tomography/computed tomography images as well as whole body autoradiograph. These
      results suggest that (188)Re-(DXR)-liposomes are potentially promising agents for
      passive targeting treatment of malignant disease.

PMID- 20150619
TI  - Sansalvamide induces pancreatic cancer growth arrest through changes in the cell
      cycle.
AB  - Survival of patients with pancreatic cancer remains poor due to inadequate
      chemotherapeutic options. Sansalvamide A, a cyclic depsipeptide produced by a
      marine fungus, has demonstrated significant anticancer activity. We previously
      observed antiproliferative effects in a series of sansalvamide A analogs in
      pancreatic cancer cells, one of which was further evaluated in this study. Two
      human pancreatic cancer cell lines (AsPC-1 and CD18) were incubated with
      increasing concentrations (10-50 muM) of the sansalvamide analog. Cell
      proliferation was then measured by thymidine incorporation and cell counting, and
      cell cycle analysis was determined by flow cytometry. Western blot analysis was
      used to evaluate expression of cyclin D1, cdk4, cdk6, cyclin E, cyclin A, cdk2,
      and p21. Sansalvamide caused G(1) phase cell cycle arrest in both cell lines, and
      Western blot analyses demonstrated up-regulation of p21, down-regulation of
      cyclins D1, E, and A, and cdk4, consistent with G(0)/G(1) cell cycle arrest.
      Cumulatively the results show that Sansalvamide A attenuates pancreatic cancer
      cell growth and represents a potential anticancer therapy.

PMID- 20150620
TI  - Effects of silybinin on the pharmacokinetics of tamoxifen and its active
      metabolite, 4-hydroxytamoxifen in rats.
AB  - The effects of silybinin, an antioxidant, on the pharmacokinetics of tamoxifen
      and its metabolite, 4-hydroxytamoxifen, were investigated in rats. A single dose
      of tamoxifen was administered intravenously (2 mg/kg) and orally (10 mg/kg)
      without or with silybinin (0.5, 2.5 and 10 mg/kg) to rats. Silybinin
      significantly altered the pharmacokinetics of orally administered tamoxifen.
      Compared to those in the oral control group (given tamoxifen alone), the area
      under the plasma concentration-time curve (AUC(0-infinity)) and the peak plasma
      concentration (C(max)) of tamoxifen were significantly (p<0.05 for 2.5 mg/kg,
      p<0.01 for 10 mg/kg) increased by 40.2-71.3% and 45.2-78.6%, respectively, with
      silybinin. Consequently, the absolute bioavailability (AB) of tamoxifen in the
      presence of silybinin (2.5 and 10 mg/kg) was 31.1-38.1%, which was significantly
      enhanced (p<0.05) compared to that in the oral control group (22.2%). Moreover,
      the relative bioavailability (RB) of tamoxifen was 1.40- to 1.72-fold greater
      than that in the control group. Silybinin (10 mg/kg) significantly increased the
      AUC(0-infinity) (p<0.05, 40.0%) of 4-hydroxytamoxifen, but the metabolite-parent
      ratio (MR) of 4-hydroxytamoxifen was significantly altered (p<0.05 for 10 mg/kg),
      implying that the formation of 4-hydroxytamoxifen was considerably affected by
      silybinin. The enhanced bioavailability of tamoxifen by silybinin might be due to
      the promotion of intestinal absorption in the small intestine and the reduction
      of first-pass metabolism of tamoxifen in the small intestine and in the liver. If
      these results are confirmed in clinical trials, the tamoxifen dosage should be
      adjusted when tamoxifen is administered with silybinin or silybinin-containing
      dietary supplements.

PMID- 20150621
TI  - Expression of vascular endothelial growth inhibitor (VEGI) in human urothelial
      cancer of the bladder and its effects on the adhesion and migration of bladder
      cancer cells in vitro.
AB  - BACKGROUND: Vascular endothelial growth inhibitor (VEGI) has been implicated in
      the regulation of tumour-related vasculature in certain solid tumours. However,
      its role in urothelial tumours is still unclear. In the present study, the role
      played by VEGI in urothelial tumours of the bladder was investigated. MATERIALS
      AND METHODS: The expression of VEGI was examined in cancer human bladder tissues
      and in a serial of cell lines using immunochemical staining and RT-PCR
      respectively. The biological impact of modifying VEGI expression in urothelial
      cancer cells was evaluated using in vitro models. RESULTS: VEGI mRNA was
      expressed in a wide variety of human cell lines. VEGI expression was seen in
      normal urothelial and stromal cells, but was found to be reduced or absent in
      urothelial cancer cells. The positive staining in normal tissue (6/7) was
      significantly higher than that of urothelial cancer tissues (2/12), p=0.006.
      Moreover, overexpression of VEGI reduced the motility and adhesion of urothelial
      cancer cells in vitro. However, the overexpression of VEGI had no bearing on the
      growth and invasion of urothelial cancer cells. CONCLUSION: VEGI has an
      inhibitory effect on cellular motility and adhesion in bladder cancer cells.
      Taken together with the expression pattern of VEGI in urothelial cancer of the
      bladder, it suggests that VEGI functions as a negative regulator of
      aggressiveness during development and progression of bladder cancer.

PMID- 20150623
TI  - Methylation of the DCC gene is lost in advanced gastric cancer.
AB  - BACKGROUND: Deleted in colorectal carcinoma (DCC), one of the Netrin-1 receptors,
      belongs to the functional dependence receptor family, members of which share the
      ability to induce apoptosis in the absence of their ligands. Recently, we
      examined the methylation status of the DCC gene in colorectal carcinomas and
      found that aberrant methylation of the DCC gene was detected in 28 out of the 50
      (56%) primary colon carcinomas. This result prompted us to examine the
      methylation status of the DCC gene in gastric carcinoma. MATERIALS AND METHODS:
      The methylation status of the DCC gene was examined in primary carcinomas and the
      corresponding normal tissues derived from 36 patients with gastric cancer using
      quantitative methylation-specific polymerase chain reaction (qMSP) and the
      correlation between the methylation status and the clinicopathological findings
      was evaluated. RESULTS: Aberrant methylation of the DCC gene was detected in 16
      out of the 36 (44%) primary gastric carcinomas. A significant difference was
      observed in regard to the TNM stage (p=0.0093). CONCLUSION: DCC methylation was
      observed in the course of gastric carcinogenesis and disappeared in advanced
      gastric carcinoma.

PMID- 20150622
TI  - Distinct roles of cholinergic receptors in small cell lung cancer cells.
AB  - BACKGROUND: Cholinergic receptors are expressed in small cell lung cancer (SCLC);
      however, the distinct functions of muscarinic cholinergic receptor 3 (mAChR3) and
      the nicotinic cholinergic receptor (nAChR) in SCLC have not yet been completely
      elucidated. MATERIALS AND METHODS: RT-PCR and Western blotting were used to
      investigate the expression of cholinergic receptors. Flow cytometry was used to
      detect the integrin expression. Cell proliferation, adhesion and migration assays
      were carried out in vitro to determine the roles of the cholinergic receptors in
      SBC3 human SCLC cells. RESULTS: Both mAChR3 and nAChR were expressed in the SBC3
      cells. Acetylcholine iodide (Ach) stimulated SBC3 cell proliferation, adhesion
      and migration toward fibronectin (Fn). The mAChR3 antagonist, 4-diphenylacetoxy-N
      methylpiperidine methiodide (4-DAMP), or the nAChR antagonist, mecamylamine
      hydrochloride (Meca), inhibited SBC3 cell proliferation in the presence or the
      absence of exogenous Ach. 4-DAMP abrogated cell adhesion and migration toward Fn
      induced by Ach, while Meca had no effect. Interestingly, Ach did not alter Fn
      receptor (alphavbeta1 or alpha5beta1 integrin) expression, while anti-beta1
      integrin antibody or anti-alphav and anti-alpha5 integrin antibody completely
      abrogated cell adhesion to Fn induced by Ach. CONCLUSION: Both mAChR3 and nAChR
      are expressed in SCLC. SBC3 cell proliferation is regulated in vitro through both
      cholinergic receptors. In contrast, SBC3 cell migration and adhesion toward Fn
      are modulated only by mAChR. Moreover, the stimulatory effects of Ach on cell
      adhesion and migration through mAChR3 are presumably modulated by functional
      alteration of alphavbeta1 and alpha5beta1 integrin, but not by any variation in
      their expression. The mAChR3 antagonist may therefore be a beneficial therapeutic
      modality for SCLC patients, especially those with chronic obstructive pulmonary
      disease (COPD) as a comorbidity.

PMID- 20150624
TI  - Cancer preventive effect of Kumaizasa bamboo leaf extracts administered prior to
      carcinogenesis or cancer inoculation.
AB  - BACKGROUND: Kumaizasa bamboo found in Hokkaido is used for traditional medicine
      in Japan. The cancer preventive effect of vigorous (multistep) hot water extract
      of Kumaizasa was examined in relation to immunological conditioning and free
      radical scavenging activity. MATERIALS AND METHODS: Cytokine induction in mice,
      free radical scavenging activity in vitro, and cancer preventive effect by oral
      administration of the vigorous extracts prior to tumor implantation or
      carcinogenesis by 7,12-dimethylbenz[a]anthracene (DMBA) were examined. RESULTS:
      In tumor inoculated mouse models (S-180 sarcoma, Meth-A fibrosarcoma, B16-F10
      melanoma), the vigorous extracts from Kumaizasa bamboo leaves suppressed tumor
      growth and prolonged survival significantly. In the chemical carcinogenesis model
      suppression of cancer incidence on day 100, tumor size and survival time were
      significantly improved with the vigorous extract, at/or above 0.03% in the diet,
      when given two weeks prior to the administration of the carcinogen. CONCLUSION:
      The vigorous extracts of bamboo leaf show immunopotentiating and radical
      scavenging effects and administration prior to carcinogen exposure or tumor
      inoculation significantly suppresses tumor incidence and tumor growth and
      prolongs survival.

PMID- 20150625
TI  - Mifepristone treatment improves length and quality of survival of mice with
      spontaneous lung cancer.
AB  - BACKGROUND: There are data showing that human leukemia cell lines have mRNA for
      an immunomodulatory protein found in normal pregnancy that is stimulated by
      progesterone. One of the functions of this progesterone-induced blocking factor
      (PIBF) is to suppress natural killer cell activity. Mifepristone has not only
      been shown to down-regulate PIBF expression by human leukemic cell lines but has
      also been shown to prolong and improve the length of life of mice with
      spontaneous leukemia. MATERIALS AND METHODS: Mifepristone at 0.3 mg was gavaged
      three times weekly from 8 weeks vs. olive oil in the controls. RESULTS: The
      survival at one year for mice treated with mifepristone was 57.6% vs. 26.6% for
      controls (p=0.056). There were 66.7% of mice treated with mifepristone with no
      sick days whereas there was not one control mouse that did not become sick within
      the first year. The mean number of days sick was 11.6 for mifepristone vs. 57.6
      days for controls (p=0.05) and 66.7% of the survival group had no sick days vs.
      none of the controls. CONCLUSION: These data suggest a possible novel cancer
      therapy using progesterone receptor antagonist drugs even in tumors not known to
      have progesterone receptors to try to change the tumor microenvironment and re
      activate suppressed natural killer cells.

PMID- 20150626
TI  - Does dexamethasone inhibit the antineoplastic effect of cisplatin and docetaxel
      in head and neck cancer cells?
AB  - BACKGROUND/AIM: Comedication with glucocorticoids such as dexamethasone is
      frequently given to head and neck cancer patients treated with chemotherapy.
      However, an increasing body of evidence suggests that dexamethasone may induce
      resistance to antineoplastic agents. The present study was the first to
      investigate the effect of dexamethasone on the antiproliferative activity of
      cisplatin and docetaxel in vitro in squamous cell carcinoma of the head and neck
      (SCCHN) cell lines. MATERIALS AND METHODS: The cytotoxic effect of cisplatin and
      docetaxel on eight SCCHN cell lines was determined for each drug alone or with
      increasing concentrations of dexamethasone. Cell growth inhibition and viability
      were measured quantitatively after 24, 48, 72 hours of treatment using water
      soluble-tetrazolium-test and lactate dehydrogenase assays. Absolute tumor cell
      numbers were determined by cell counting in a Rosenthal chamber. RESULTS:
      Cisplatin and docetaxel alone inhibited the growth of all eight SCCHN cell lines
      significantly (p=0.012). The antiproliferative activity of both agents was not
      decreased by the addition of dexamethasone in any of the cell lines (p>0.05).
      CONCLUSION: Dexamethasone does not interfere with the cytotoxic action of
      cisplatin or docetaxel in the investigated SCCHN cell lines.

PMID- 20150627
TI  - Quantitative structure-cytotoxicity relationship of newly synthesized tropolones
      determined by a semiempirical molecular-orbital method (PM5).
AB  - A semiempirical molecular-orbital method (CONFLEX/PM5) was applied to delineate
      the relationship between the cytotoxicity (evaluated by 50% cytotoxic
      concentration, CC(50)) of twenty-four tropolone-related compounds and their
      molecular weight or one of the following eleven chemical descriptors: the heat of
      formation (COSMO, non-COSMO; kcal/mole), stability of hydration (=COSMO-nonCOSMO
      (DeltaH); kcal/mole), dipole moment (D), hydrophobicity (log P), highest occupied
      molecular orbital energy (E(HOMO); eV), lowest unoccupied molecular orbital
      energy (E(LUMO); eV), absolute hardness [eta=(E(LUMO)-E(HOMO))/2; eV)], absolute
      electron negativity [chi=-(E(LUMO)+E(HOMO))/2; eV], reactivity index
      (omega=chi(2)/2eta; eV), surface area (A(2)) and volume (A(3)) of the molecule.
      No good correlation was found with the unseparated twenty-four compounds all
      together, but modest to high correlation was found after separation into three
      different groups of compounds, depending on the structural similarity. Particular
      descriptors could be used to evaluate the biological activity of newly
      synthesized tropolones.

PMID- 20150628
TI  - Effects of alphavbeta6 gene silencing by RNA interference in PANC-1 pancreatic
      carcinoma cells.
AB  - BACKGROUND: Integrin alphavbeta6 is up-regulated in a variety of human carcinomas
      and plays a crucial role in tumor invasion and metastasis. However, the function
      of alphavbeta6 in pancreatic carcinoma and its potential role in gemcitabine
      resistance remain unknown. MATERIALS AND METHODS: Small interfering RNA (siRNA)
      targeting alphavbeta6 was constructed and transfected into PANC-1 cells. Effects
      of alphavbeta6 knockdown on cell proliferation, invasion, cell cycle progression,
      apoptosis and chemosensitivity to gemcitabine were investigated. RESULTS:
      Expression of alphavbeta6 in PANC-1 cells was markedly suppressed by siRNA.
      Silencing of alphavbeta6 expression significantly inhibited cell proliferation
      and invasiveness, resulted in cell cycle arrest, and induced cell apoptosis. More
      importantly, alphavbeta6 knockdown enhanced chemosensitivity to gemcitabine and
      increased gemcitabine-induced caspase-mediated apoptosis. CONCLUSION: These
      findings suggest a novel mechanism by which alphavbeta6 contributes to pancreatic
      carcinoma progression. The combination of alphavbeta6 silencing and gemcitabine
      treatment may provide an effective therapeutic strategy for highly resistant
      pancreatic carcinoma.

PMID- 20150629
TI  - Blue light is phototoxic for B16F10 murine melanoma and bovine endothelial cell
      lines by direct cytocidal effect.
AB  - The large number of studies devoted to the effect of ultraviolet light on
      biological systems, contrasts with the lack of experimental data concerning the
      direct effects of visible light. It has been shown that blue light inhibited the
      growth of B16F10 melanoma cell lines and reduced the percentage of S phase cells.
      Yet these effects are poorly understood. MATERIALS AND METHODS: Two cell lines
      and irradiation with blue light were used. Cell mortality and a possible
      mechanism of action were investigated. RESULTS: Exposure of B16F10 melanoma and
      bovine endothelial cells to blue light (wavelength 450 nm, 10 J/cm(2) from a
      Waldman lamp) induced a rapid and large reduction in viability followed by the
      death of virtually all the irradiated cells within 24 h. These results led us to
      expose a patient with haemorrhagic cutaneous melanoma metastasis to blue light.
      Irradiation led to an immediate arrest of haemorrhage, an inhibition of tumour
      growth and extensive tumour necrosis 24h after irradiation. CONCLUSION: Exposure
      to blue light may offer new approaches to the treatment of superficial skin
      carcinomas in humans.

PMID- 20150631
TI  - PPARgamma ligand 15-deoxy-delta 12,14-prostaglandin J2 sensitizes human colon
      carcinoma cells to TWEAK-induced apoptosis.
AB  - BACKGROUND: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been
      shown to induce colon cancer cell apoptosis in the presence of interferon-gamma.
      We hypothesized that co-treatment using TWEAK with other pro-apoptosis agents
      could sensitize death receptor-resistant colon cancer cells. MATERIALS AND
      METHODS: The effects of chemopreventive agents and TWEAK on cell death and
      apoptosis were determined using propidium iodide (PI) exclusion and M30
      CytoDEATH. RESULTS: We found that 15d-PGJ(2) sensitizes colon cancer cells to
      TWEAK-induced apoptosis. Caspase inhibition reduced 15d-PGJ(2)-, but not 15d
      PGJ(2)+TWEAK-induced apoptosis. 15d-PGJ(2) promoted reactive oxygen species (ROS)
      production and dissipation of mitochondrial potential (DeltaPsi(m)) that were
      more marked with combined treatment. ROS, DeltaPsi(m) and cell death were
      partially normalized by the antioxidant N-acetylcysteine. TWEAK induced nuclear
      factor-kappa B activation, which was attenuated by 15d-PGJ(2). 15d-PGJ(2) reduced
      the expression of the anti-apoptotic proteins BCL-X(L) and MCL-1, while
      increasing BAX and translocation of cytochrome c and apoptosis-inducing factor.
      CONCLUSION: 15d-PGJ(2) sensitized cancer cells to TWEAK-induced apoptosis through
      an ROS-dependent cell death pathway and may have chemotherapeutic utility as an
      apoptosis-enhancing agent.

PMID- 20150630
TI  - The cytotoxic agents NSC-95397, brefeldin A, bortezomib and sanguinarine induce
      apoptosis in neuroendocrine tumors in vitro.
AB  - The aim of this study was to investigate the apoptosis resulting from NSC 95397,
      brefeldin A, bortezomib and sanguinarine in neuroendocrine tumor cell lines.
      MATERIALS AND METHODS: A multiparametric high-content screening assay for
      measurement of apoptosis was used. The human pancreatic carcinoid cell line, BON
      1, human typical bronchial carcinoid cell line NCI-H727 and the human atypical
      bronchial carcinoid cell line NCI-H720 were tested. After incubation with
      cytotoxic drugs, the DNA-binding dye Hoechst 33342, fluorescein-tagged probes
      that covalently bind active caspase-3 and chloromethyl-X-rosamine to detect
      mitochondrial membrane potential were added. Image acquisition and quantitative
      measurement of fluorescence was performed using automated image capture and
      analysis instrument ArrayScan. In addition, nuclear morphology was examined on
      microscopic slides stained with May-Grunewald-Giemsa. RESULTS: A time- and dose
      dependent activation of caspase-3 and increase in nuclear fragmentation and
      condensation were observed for the drugs using a multiparametric apoptosis assay.
      These results were confirmed with nuclear morphological examination on
      microscopic slides. CONCLUSION: NSC 95397, brefeldin A, bortezomib and
      sanguinarine induced caspase-3 activation with modest changes in nuclear
      morphology.

PMID- 20150632
TI  - Phase I trial of fixed-dose rate gemcitabine in combination with bortezomib in
      advanced solid tumors.
AB  - BACKGROUND: Bortezomib demonstrates synergism with gemcitabine via a fixed-dose
      rate (FDR). The aim of this phase I trial in solid tumors was to establish the
      maximum tolerated dose (MTD) and safety data for this combination. PATIENTS AND
      METHODS: Twenty-nine patients with a median age of 63 (range 36-84) years and
      median Karnofsky Performance Status of 90 (range 60-100) were enrolled and
      treated with bortezomib (1.0 or 1.3 mg/m(2)) on days 1, 4, 8 and 11 and FDR
      gemcitabine (750, 1,000, or 1,250 mg/m(2)) on days 1 and 8 of each 21-day cycle.
      Response was evaluated every two cycles. RESULTS: Dose-limiting toxicities were
      grade 4 thrombocytopenia and neutropenia and grade 3 liver function test
      abnormalities. The MTD was bortezomib 1 mg/m2 and FDR gemcitabine 1,250 mg/m(2).
      The median number of cycles delivered was 3 (range 1-28). There was one partial
      response and six cases of stable disease. The median duration of response was 8.5
      (range 3-20) months. CONCLUSION: FDR gemcitabine and bortezomib combination can
      be delivered effectively with acceptable toxicity.

PMID- 20150633
TI  - Image DNA cytometry in FNABs of Libyan breast disease.
AB  - BACKGROUND: The sensitivity for identification of malignant cells in conventional
      fine-needle aspiration biopsy (FNAB) investigation is about 80%. This percentage
      is dependent on the number of examined cells, type of breast cancer, and
      experience of the examiner. The aim of our study was to estimate the supporting
      value of image DNA cytometry of FNAB of the breast, and do so by using different
      sampling methods. MATERIALS AND METHODS: This retrospective study was based on 41
      cases with an available histological diagnosis: 18 benign lesions and 23
      malignant tumours were examined. The smears were submitted to image DNA analysis
      in a three-step protocol: (i) smears stained with HE method were destained and
      (ii) then restained with Feulgen staining for DNA and (iii) finally analysed
      using image cytometry. RESULTS: All non-malignant cases had diploid histogram.
      However, a few of them had one or two cells of >5c category. Most histologically
      malignant cases were aneuploid. Only three invasive ductal carcinomas showed
      diploid histograms. All samples with aneuploid histograms were malignant.
      CONCLUSION: The results confirm earlier published data in the Finnish population
      and indicate that image DNA cytometric analysis of nuclear content is a useful
      marker for identification of malignant cells in FNAB, especially after free cell
      sampling. The method can be used to increase the cytological sensitivity and
      specificity in doubtful breast lesions.

PMID- 20150634
TI  - Clinical value of preoperative lymphoscintigraphy in patients with early cervical
      cancer considered for intraoperative lymphatic mapping.
AB  - The purpose of this study was to examine the clinical usefulness of preoperative
      lymphoscintigraphy (PLS) for sentinel node identification in patients undergoing
      lymphatic mapping during surgery for early cervical cancer. PATIENTS AND METHODS:
      Day-before PLS was performed in 42 patients who were candidates for open radical
      hysterectomy and intraoperative lymphatic mapping, using a combination of
      radiocolloid and blue dye technique. RESULTS: In 39 patients, at least one
      sentinel node (SN) was evident either in the lymphoscintigram or during the
      operation (detection rate 92.8%). Lymphoscintigraphy revealed unilateral SNs in
      24 (61.5%) cases and bilateral SNs in 15 (38.5%). A total of 56 SNs were
      identified. Intraoperatively, 5 out of 24 patients with unilateral SNs on PLS had
      bilateral identification. The total number of SNs retrieved was 103
      (2.6/patient). While one SN was identified in 25 cases on PLS, 32 patients had
      two or more SNs intraoperatively. The agreement between preoperative and
      intraoperative detection regarding laterality, number and location of SNs was
      poor (Kappa<0.69). CONCLUSION: PLS is of limited clinical value for
      intraoperative SN detection in early cervical cancer.

PMID- 20150635
TI  - A multicountry ecological study of risk-modifying factors for prostate cancer:
      apolipoprotein E epsilon4 as a risk factor and cereals as a risk reduction
      factor.
AB  - The primary risk-modifying factors for prostate cancer are still a matter of
      debate. This work proposes and examines the hypothesis that the apolipoprotein E
      epsilon4 (ApoE4) allele and diet are important risk factors for prostate cancer.
      The hypothesis was evaluated in an ecological study involving 122 countries for
      which prostate cancer rates for 2002, ApoE4 allele prevalence, dietary supply
      values, and per capita gross domestic product (GDP) data were available, and for
      which there were at least 250,000 inhabitants. In addition, a subset of 102
      countries with ApoE4 prevalence of less than 30% was also used. In the full data
      set, per capita GDP, lack of cereal consumption, milk protein and ApoE4 were
      significantly correlated with incidence, explaining 60% of the variance. In the
      102-country subset of 102, per capita GDP, ApoE4 prevalence, and milk protein
      explained 62% of the variance of prostate cancer incidence, while lack of cereal
      consumption, ApoE4 prevalence and per capita GDP explained 55% of the variance of
      prostate cancer mortality rates. Cholesterol has been identified as an important
      risk factor for prostate cancer. The ApoE4 allele increases cholesterol
      production and cereal consumption lowers serum cholesterol levels. The ApoE4
      allele is an important risk factor for Alzheimer's disease, and cholesterol is a
      risk factor and cereals a risk reduction factor. The ApoE4-diet-GDP hypothesis
      may explain the higher risk of prostate cancer for African Americans and should
      form the basis for further studies.

PMID- 20150636
TI  - Clinicopathological variables predictive of clinical outcome in patients with
      FIGO stage Ib2-IIb cervical cancer treated with cisplatin-based neoadjuvant
      chemotherapy followed by radical hysterectomy.
AB  - The aim of this retrospective investigation was to assess the prognostic
      relevance of some pre-treatment clinical variables and histological findings
      assessed on the surgical samples of 46 patients with stage Ib(2)-IIb cervical
      cancer treated with cisplatin-based neoadjuvant chemotherapy followed by radical
      hysterectomy. Seven patients achieved a pathologically documented complete
      response, 6 had an optimal partial response, 29 had a suboptimal partial
      response, and 4 had stable disease. As for histological findings on surgical
      samples, 7 (15.2%) patients had positive lymph nodes, 10 (21.7%) had lymph
      vascular space involvement, and 10 (21.7%) had positive parametria and/ or
      surgical margins. After surgery, 38 patients received further treatment with
      chemotherapy and/or irradiation. The median follow-up of survivors was 53 months
      (range, 4-167 months).Thirteen (28.3%) patients developed recurrent tumour, 11
      (23.9%) patients died of tumour and one patient died of ictus with no clinical
      evidence of tumour. Recurrence-free and overall survival were significantly
      related to tumour stage (Ib(2)-IIa versus IIb, p=0.01 and p=0.02, respectively),
      pathologically assessed lymph node status (negative versus positive, p=0.0009 and
      p=0.007), lymph-vascular space status (negative versus positive, p=0.01 and
      p=0.009), parametrial and/or surgical margin status (negative versus positive,
      p=0.0001 and p=0.0005), but not to haemoglobin level before chemotherapy, patient
      age, tumour grade or chemotherapy regimen. A platelet count before chemotherapy
      above the median value of 272,000/microl was associated with a trend for a
      shorter recurrence-free survival (p=0.06) and with a significantly shorter
      overall survival (p=0.04) when compared with a lower platelet count. In
      conclusion, FIGO stage, lymph node status, lymph-vascular space status,
      parametrial and/or surgical margin status and pre-treatment platelet count are
      predictors of clinical outcome in patients with FIGO stage Ib(2)-IIb cervical
      cancer undergoing cisplatin-based neoadjuvant chemotherapy followed by radical
      hysterectomy. A multivariate analysis on a larger series of homogeneously treated
      patients is warranted to better define the clinicopathological risk factors
      useful to adequately plan the therapeutic strategy.

PMID- 20150637
TI  - Prolonged disease control after myeloablative chemotherapy, autologous
      transplantation and immunotherapy in high-risk early breast cancer.
AB  - BACKGROUND: Failure to eradicate all cancer stem cells, lymphocytopenia, and high
      levels of vascular endothelial growth factor (VEGF) may explain the limited
      efficacy of high dose-chemotherapy (HDCT) with peripheral progenitor cell
      transplantation (PBPCT) in high-risk early breast cancer with more than 10
      axillary nodes (HRBC). PATIENTS AND METHODS: With the aim of increasing patient's
      lymphocyte count and reducing VEGF, wich could translate into an improved immune
      function and a better clinical outcome, patients with HRBC, received HDCT, PBPCT
      and immunotherapy with interleukin-2 (IL-2) and 13-cis retinoic acid (RA).
      RESULTS: A total of 30 HRBC patients were entered into the study. Grade 4
      hematological toxicity was universal, while major adverse effects of IL-2 were
      fever, rash and autoimmune reactions. After a median follow-up of 61 months,
      immune function improved with a statistically significant increase of lymphocyte
      count and a decrease in VEGF levels. This translated into an unexpected 5-year
      relapse-free and overall survival rates of 76% and 85%, respectively. CONCLUSION:
      These data show that IL-2 and RA administration after HDCT and PBPCT is feasible
      and, as well as giving a statistically significant improvement in lymphocyte
      count and a decrease of VEGF, also seems to improve the expected clinical
      outcome.

PMID- 20150638
TI  - Association of COMT haplotypes and breast cancer risk in caucasian women.
AB  - Catechol-O-methyl transferase (COMT) is an important estrogen-metabolizing
      enzyme, and common genetic variants in this gene could affect breast cancer risk.
      We conducted a large population-based case control study in Massachusetts, New
      Hampshire, and Wisconsin to examine six strategically selected COMT haplotype
      tagging (ht) single nucleotide polymorphism (SNPs), including the val158met
      polymorphism (rs4680), in relation to breast cancer risk. Analyses were based on
      1,655 Caucasian women with invasive breast cancer and 1,470 Caucasian controls.
      None of the six individual SNPs were associated with breast cancer risk. The
      global test for haplotype associations was nonsignificant (p-value=0.097),
      although two uncommon haplotypes present in 6% of the study population showed
      statistically significant inverse associations with risk. These results suggest
      that genetic variation in COMT has no significant association with breast cancer
      risk among Caucasian women.

PMID- 20150639
TI  - A case of esophageal cancer with multiple lymph node metastases which responded
      to neoadjuvant chemotherapy (DCF therapy).
AB  - It is difficult to perform radical surgery for esophageal cancer with multiple
      lymph node metastases. Therefore, effective neoadjuvant adjuvant treatment is
      necessary to achieve successful radical resection. The use of neoadjuvant
      chemotherapy of docetaxel, cisplatin (CDOP) and 5-fluorouracil (5-FU) (DCF) in an
      advanced case is reported. The patient (a 67-year-old female) was diagnosed with
      esophageal cancer, T3, N4, M0, stage IVa with a large number of lymph node
      metastases in the mediastinum and in the abdominal cavity. Neoadjuvant DCF
      chemotherapy was initiated in August 2006. Adverse events were mild. A complete
      response of the lymph node metastases in the abdominal cavity and a partial
      response of the esophageal lesion were achieved. The surgical procedure included
      a right thoracolaparotomy followed by a subtotal excision of the esophagus and
      two-field lymph node dissection. The cancer was diagnosed to be moderately
      differentiated squamous cell cancer, pT2, pN4(3c) and pstage IVa. The
      histological efficacy of the chemotherapy was determined to be grade 1a. Two
      additional courses of DCF therapy were administered followed by postoperative
      adjuvant chemotherapy.

PMID- 20150640
TI  - Late effects of abdominal irradiation in children: a review of the literature.
AB  - AIM: To comprehensively summarize the most important literature regarding the
      late effects of radiotherapy to the abdomen in childhood and adolescence.
      MATERIALS AND METHODS: Published trials, studies and series were identified using
      the PubMed database. The key words late effects, late sequelae, child, radiation,
      radiotherapy, abdomen, kidney, liver, and bowel were used. RESULTS: A dose-volume
      effect is confirmed for liver irradiation. Radiation with doses <20 Gy to major
      parts of the liver or higher doses to smaller parts seems to be safe. Kidney
      function impairment due to radiation is rare in children. Renal sequelae may
      occur after radiation to the remaining kidney in patients who underwent
      nephrectomy or who received higher doses to both kidneys. Several reports
      describe small bowel obstruction as a sequelae of surgery, but radiotherapy seems
      to be less important. CONCLUSION: Several retrospective reports describe
      radiation-associated late sequelae in children. However, there is still a lack of
      sufficient data regarding the characterization of dose-volume effects.

PMID- 20150641
TI  - Changes in soluble CEA and TIMP-1 levels during adjuvant chemotherapy for stage
      III colon cancer.
AB  - BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested
      to be a valuable marker in colorectal cancer (CRC), but the effects of
      chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect
      of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antigen
      (CEA) levels in patients with stage III colon cancer. PATIENTS AND METHODS:
      Thirty patients who had been curatively resected for stage III colon cancer were
      included. The patients received 10-12 cycles of modified FOLFOX6 regimen. Blood
      samples were collected before and after the first and the second cycle and three
      months later. RESULTS: No significant change could be detected in CEA levels
      while TIMP-1 raised significantly after the second cycle but returned to normal 3
      months later. CONCLUSION: Plasma CEA levels are stable during adjuvant
      chemotherapy while the plasma level of TIMP-1 might be directly affected by
      chemotherapy represented by a transient rise about 2 weeks following the
      initiation of treatment.

PMID- 20150642
TI  - CpG island promoter methylation (CIHM) status of tumor suppressor genes
      correlates with morphological appearances of gastric cancer.
AB  - CpG island hypermethylation (CIHM) of tumor suppressor genes is one of the major
      events in the gastric carcinogenesis. We aimed to investigate the association
      between CIHM status of tumor suppressor genes and clinicopathological and
      morphological characteristics of gastric cancer. PATIENTS AND METHODS: CIHM of
      p14, p16, Death-associated protein kinase (DAPK) and E-cadherin (CDH1) genes were
      determined by methylation-specific-polymerase chain Reaction in 146 gastric
      cancer tissues. CIHM-high was defined as three or more methylated CpG islands.
      RESULTS: CIHM pf p14 was found in 70 (47.9%) cases, in 26 (17.8%) for p16, in 104
      (71.2%) for CDH1 and in 127 (87.0%) for DAPK. CIHM-high was also found in 63
      cases (43.2%). No association was found between between CIHM status and different
      staging, Lauren's subtypes, anatomic location, venous and lymphatic invasion,
      lymph node metastasis, distant metastasis, or peritoneal dissemination. However,
      among early gastric cancer cases, the depressed type with ulceration presented a
      significantly lower prevalence of CIHM of DAPK. In addition, Borrmann type IV
      cases presented significantly lower prevalence of CIHM-high among advanced
      gastric cancer. The Borrmann type IV cases also presented lower mean methylation
      number. CONCLUSION: The present results suggest that CIHM of DAPK and CIHM-high
      were associated with the morphological appearance of depressed type with
      ulceration in early gastric cancer, and Borrmann type IV advanced gastric cancer,
      respectively.

PMID- 20150643
TI  - Absence of oncogenic mutations of RAS family genes in soft tissue sarcomas of 100
      Japanese patients.
AB  - BACKGROUND: Activating point mutations of genes of the RAS family (KRAS, HRAS and
      NRAS genes) are frequently found in carcinomas, but their prevalence in sarcomas
      varies considerably among ethnic groups. No extensive studies in Japanese
      patients have been performed. MATERIALS AND METHODS: Mutation analyses of three
      RAS genes (KRAS, HRAS and NRAS) were performed using polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP) analyses and PCR direct
      sequencing in one hundred cases of soft tissue sarcoma (STS) as well as six STS
      cell lines from Japanese patients. RESULTS: No mutations were found in two hot
      spot regions (codon 12-13 and 61) of the three RAS genes. CONCLUSION: Activating
      mutations of the RAS gene family are uncommon events in soft tissue sarcomas in
      Japanese patients.

PMID- 20150644
TI  - Evaluation of the prognostic value of CD44 in glioblastoma multiforme.
AB  - BACKGROUND/AIM: Glioblastoma and astrocytoma are the most common brain tumors
      affecting adults 45-60 years of age. The poor prognosis for glioblastoma patients
      results from recurrence after treatment. There is therefore an urgent need to
      develop diagnostic and prognostic markers as well as new therapies. PATIENTS AND
      METHODS: Microarray analyses of clinical specimens from glioblastoma patients
      were used to identify potential tumor markers. Expression of candidate genes was
      analyzed by real-time reverse transcription-polymerase chain reaction and by
      immunoblotting and immunohistochemistry. RESULTS: Five potential markers (CD44
      antigen (CD44), growth arrest and DNA-damage-inducible, alpha (GADD45A),
      fibronectin 1 (FN1), CD63 antigen (CD63) and secreted phosphoprotein 1 (SPP1))
      showed expression patterns that correlated significantly with malignant glioma.
      In particular, expression of the CD44 antigen was elevated in more severe tumor
      types, and higher in tumor cores than in peripheral regions. However, lower
      levels of CD44 expression surprisingly correlated with lower survival.
      CONCLUSION: The CD44 antigen is a promising candidate for further development as
      a prognostic and therapeutic tool.

PMID- 20150645
TI  - Massive fundic gland polyposis in a patient receiving protracted proton-pump
      inhibitor medication.
AB  - A case of massive fundic gland polyposis (MFGPsis) in a female patient receiving
      protracted proton-pump inhibitor (PPI) medication is described. At gross
      examination the majority of the polyps were overlapping, confluent, some of them
      having a "cauliflower-like" configuration. The fundic gland polyps (FGP) arose in
      the gastric acid secretory mucosa. The confluence of these polyps impeded their
      enumeration. The gross and histological characteristics of this case seemed to be
      at variance with syndromic or sporadic cases having multiple FGP, inasmuch as in
      this case, the FGP had a propensity to agglutinate, to overlap and to develop
      confluent macrocysts. Another difference was that this disease, refractory to
      antacid treatment, required surgical intervention. This case substantiates the
      notion that protracted PPI medication may encourage the development of MFGPsis in
      susceptible individuals.

PMID- 20150646
TI  - Prognostic significance of nuclear DJ-1 expression in astrocytoma.
AB  - The present study was conducted to determine whether any correlation exists
      between the expression of DJ-1 and WHO grading of the tumor or patient prognosis,
      and to analyze the function of this oncogene in astrocytomas. Twenty-nine
      formalin-fixed and paraffin-embedded glioblastomas (grade IV), 21 anaplastic
      astorocytomas (grade III), and 14 diffuse astrocytomas (grade II) were
      immunohistochemically studied to identify the expression of DJ-1 protein. The
      expression of DJ-1 was detected both in the nucleus and cytoplasm of tumor cells;
      however, such expression varied from case to case. While there was no difference
      in the cytoplasmic expression of DJ-1 among astrocytomas, its nuclear expression
      was inversely correlated with the WHO grading of astrocytomas. Moreover, the
      overall survival of patients with maintained (group 1) or mixed (groups 2 and 3)
      was significantly longer than those with decreased (group 3) expression
      (p=0.0063). The present study demonstrated that the survival of patients with
      astrocytomas was correlated with the nuclear DJ-1 status of the tumor. We herein
      demonstrated for the first time that the DJ-1 molecule might therefore play an
      important role as a tumor suppressor in astrocytomas.

PMID- 20150647
TI  - Primary effusion lymphoma in two HIV-negative patients successfully treated with
      pleurodesis as first-line therapy.
AB  - Primary effusion lymphoma (PEL) is a rare non-Hodgkin's lymphoma (NHL) mostly
      occurring in HIV-positive patients. It is characterized by the development of
      effusion in one or more body cavities, with no tumor masses and a positive human
      herpes virus-8 (HHV8) status. It has a poor survival profile and no optimal
      treatment is yet defined. We report two HIV-negative, HHV8-positive patients with
      PEL of the pleural cavity who achieved a durable remission after pleurodesis with
      bleomycin and no systemic therapy. We also perform a review of the relevant
      literature regarding the clinical data, treatment, and survival of PEL in HIV
      negative patients.

PMID- 20150651
TI  - Comparing intra-familial and extra-familial child sexual abusers with
      professionals who have sexually abused children with whom they work.
AB  - The aim of this study is to establish whether professionals who have sexually
      molested children with whom they work present as a homogeneous group identifiable
      by their personal histories, offending patterns, and profiles as distinct from
      other child molesters (intra-familial and extra-familial offenders). Participants
      were matched on age and IQ. It was found that child molesters who were
      professionals (similar to extra-familial offenders generally) were likely to have
      sexually abused male, or both male and female, children and had abused more than
      20 child victims. Professionals were also significantly more likely to have
      offended against post-pubescent children than were extra-familial or intra
      familial offenders. In terms of psychological profiles, professionals, like extra
      familial offenders, were found to have a significantly higher level of reported
      sexual pre-occupation and emotional over-identification with children compared
      with intra-familial offenders and a significantly lower level of distorted sexual
      attitudes about their victims compared with extra-familial offenders. These
      results are discussed in the context of assessment that might be used to assess
      risk in those working with children in a professional capacity.

PMID- 20150652
TI  - The effect of organisational context variables on employer attitudes toward
      employability of ex-offenders.
AB  - The authors tested the premise that organisational context variables (i.e., size
      of organisation, industry type, location, and respondent's position in
      organisation) had significant effects on employer (N = 596) attitudes toward
      employability of ex-offenders. They also examined whether organisational context
      variables had an equivalent effect on employer attitudes to that of job-seeker
      criminal history and employer personal characteristics (e.g., respondent age and
      gender). Using linear regression (HLM 6.02a), organisational context variables
      were shown to have a significant effect on employer attitudes. In addition,
      organisational context variables had a significantly greater effect on employer
      attitudes than did employer personal characteristics. However, job-seeker
      criminal history contributed more to respondent ratings of ex-offender
      employability than did organisational context variables. The finding that
      judgements of employability are influenced by organisational context variables
      has implications for future research relevant to reintegration. Stakeholder
      attitudes toward the reintegration success of ex-offenders may be generally
      influenced by context variables.

PMID- 20150653
TI  - Risk assessment instruments in repeat offending: the usefulness of FOTRES.
AB  - Research in the area of predicting recidivism has produced several well-validated
      standardized risk assessment instruments. The question arises, which instruments
      best serve which purposes? The objective of this study was to evaluate and
      compare several actuarial and dynamic risk assessment instruments as to their
      predictive accuracy and their usefulness in forensic practice. The sample
      consisted of 109 violent and sex offenders who had been released from prison in
      Switzerland between 1994 and 1999, and for whom the Psychopathy Checklist-Revised
      (PCL-R); Historical, Clinical, Risk Management-20; Level of Service Inventory
      Revised; Violence Risk Appraisal Guide (VRAG); and the Swiss assessment
      instrument FOTRES were scored. Using bivariate logistic regression analyses, all
      instruments were able to discriminate between recidivists and nonrecidivists. The
      receiver operating characteristic analyses yielded area under the curve values
      between 0.70 (VRAG) and 0.84 (PCL-R). Furthermore, it was shown that solely
      examining AUC values does not suffice to determine usefulness. A comprehensive
      evaluation of an instrument's usefulness for forensic practice should also look
      at qualitative criteria such as area of application, specificity of risk
      assessed, and inclusion of dynamic items among others.

PMID- 20150654
TI  - Pre- and postoccupancy evaluation of new dementia care cottages.
AB  - Concerns about negative outcomes associated with relocating residents are common.
      Fifty-five residents of a traditional high-care nursing home moved to new,
      purpose-built, dementia-specific cottages; 35 additional residents moved into the
      cottages within the first 8 months of operation. Direct-care staff participated
      in workshops on engaging residents in life-skill activities. Resident behavior
      was observed using a time sampling and a de-identified behavior mapping
      procedure. Results showed increases in resident engagement following the move and
      further increases after staff training. Staff engagement in resident interactive
      tasks similarly increased both after the move and again after staff training. The
      newly built cottages scored higher across all domains of 3 different types of
      environmental assessment, and family satisfaction ratings also improved. These
      results suggest that relocation need not negatively affect residents with
      dementia and that this environment provides an attractive model of care for
      dementia facilities.

PMID- 20150655
TI  - Environmental interventions and the design of homes for older adults with
      dementia: an overview.
AB  - In Western societies, the vast majority of people with dementia live at home and
      wish to remain doing so for as long as possible. Aging in place can be
      facilitated through a variety of environmental interventions, including home
      modifications. This article provides an overview of existing design principles
      and design goals, and environmental interventions implemented at home, based on
      literature study and additional focus group sessions. There is a multitude of
      design principles, design goals, and environmental interventions available to
      assist with activities of daily living and functions, although few systematic
      studies have been conducted on the efficacy of these goals and interventions. The
      own home seems to be a largely ignored territory in research and government
      policies, which implies that many problems concerning aging in place and
      environmental interventions for dementia are not adequately dealt with.

PMID- 20150656
TI  - Stochastically ordered multiple regression.
AB  - In various application areas, prior information is available about the direction
      of the effects of multiple predictors on the conditional response distribution.
      For example, in epidemiology studies of potentially adverse exposures and
      continuous health responses, one can typically assume a priori that increasing
      the level of an exposure does not lead to an improvement in the health response.
      Such an assumption can be formalized through a stochastic ordering assumption in
      each of the exposures, leading to a potentially large improvement in efficiency
      in nonparametric modeling of the conditional response distribution. This article
      proposes a Bayesian nonparametric approach to this problem based on
      characterizing the conditional response density as a Gaussian mixture, with the
      locations of the Gaussian means varying flexibly with predictors subject to
      minimal constraints to ensure stochastic ordering. Theoretical properties are
      considered and Markov chain Monte Carlo methods are developed for posterior
      computation. The methods are illustrated using simulation examples and a
      reproductive epidemiology application.

PMID- 20150658
TI  - [Antidepressive efficacy of quetiapine XR in unipolar major depression--the role
      of early onset of action and sleep-improving effect in decreasing suicide risk].
AB  - Although the possibilities of antidepressive pharmacotherapy are continuously
      improving, the rate of nonresponders or partial responders is still relatively
      high. Suicidal behaviour, the most tragic consequence of untreated or
      unsuccessfully treated depression, commonly develops in the first few weeks of
      antidepressive treatment before the onset of therapeutic action and is strongly
      related to certain specific symptoms of depression like anxiety, agitation and
      insomnia. The present paper reviews the newly discovered and well-documented
      antidepressive effect of quetiapine in bipolar and unipolar depression with
      special regards to its early onset of action, and its sleep-improving effects.
      Both beneficial effects play an important role in the reduction of suicidal risk
      frequently seen in depressed patients.

PMID- 20150657
TI  - A role for Sp1 in transcriptional regulation of phosphatidylethanolamine N
      methyltransferase in liver and 3T3-L1 adipocytes.
AB  - Phosphatidylcholine is made in all nucleated mammalian cells via the CDP-choline
      pathway. Another major pathway for phosphatidylcholine biosynthesis in liver is
      catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). We have now
      identified 3T3-L1 adipocytes as a cell culture model that expresses PEMT
      endogenously. We have found that PEMT mRNA and protein levels increased
      dramatically in 3T3-L1 cells upon differentiation to adipocytes. 5'-Deletion
      analysis of the PEMT promoter-luciferase constructs stably expressed in 3T3-L1
      adipocytes identified a regulatory region between -471 and -371 bp (relative to
      the transcriptional start site). Competitive and supershift assays demonstrated
      binding sites for transcription factors Sp1, Sp3 (-408 to -413), and YY1 (-417 to
      -420). During differentiation of 3T3-L1 cells to adipocytes, the amount of Sp1
      protein decreased by approximately 50% just prior to activation of PEMT.
      Transduction of 3T3-L1 adipocytes with retrovirus containing Sp1 cDNA
      demonstrated that Sp1 inhibited PEMT transcriptional activity. Similarly, short
      hairpin RNA directed against Sp1 in 3T3-L1 adipocytes enhanced PEMT
      transcriptional activation. Chromatin immunoprecipitation assays confirmed that
      Sp1 binds to the PEMT promoter, and this interaction decreases upon
      differentiation to adipocytes. These experiments directly link increased PEMT
      expression in adipocytes to decreased transcriptional expression of Sp1. In
      addition, our data established that Sp1 binding was required for tamoxifen
      mediated inhibition of Pemt promoter activity.

PMID- 20150659
TI  - [Slowing the age-induced decline of brain function with prophylactic use of (-)
      deprenyl (Selegiline, Jumex). Current international view and conclusions 25 years
      after the Knoll's proposal].
AB  - Due primarily to developments in immunology, chemotherapy and hygiene the
      estimated life expectancy at birth increased during the last century from about
      55 years to 80 years. Since the human Technical Life Span (TLSh) is about 120
      years and life expectancy is today steadily increasing by about 2.2 months/year,
      a life span of 100 years may appear quite soon. Knoll developed (-)-deprenyl, the
      first anti-aging drug, the prophylactic administration of which increased
      significantly the average life span of animals. (-)-Deprenyl became a world-wide
      used experimental tool as the first selective inhibitor of B-type MAO and being
      the unique MAO inhibitor free of the cheese effect was introduced to treat
      Parkinson's disease, because it could be administered in combination with
      levodopa without side effects. However, Knoll demonstrated in his later work that
      (-)-deprenyl has enhancing qualities already in femto-picomolar concentrations,
      which leave MAO-B activity unchanged, and the activity of the catecholaminergic
      neurons in the brain stem and this previously unknown 'enhancer effect' is
      responsible for the peculiar therapeutic benefits caused by (-)-deprenyl. Knoll
      proposed 25 years ago to slow the aging of the brain, the decay of behavioral
      performance, prolong life, and prevent or delay the onset of age-related
      neurodegenerative diseases such as Parkinson's and Alzheimer's via the
      prophylactic daily administration of 1 mg (-)-deprenyl. At present (-)-deprenyl
      belongs to the best known anti-aging drugs and a rapidly growing number of people
      are already trying to slow the aging of their brain by taking (-)-deprenyl as a
      prophylactic agent. Nevertheless, up to the present, an exact analysis with
      placebo control of the capacity of (-)-deprenyl to prevent or delay the onset of
      neurodegenerative diseases is still missing. It is already very much on the map
      to perform such a study with this world-wide highly esteemed Hungarian drug.

PMID- 20150660
TI  - Disturbance of perception in depressive disorders in the different diagnostical
      systems.
AB  - INTRODUCTION: Disturbances of perception play a considerable role in depressed
      patients' symptoms. These symptoms are mostly secondary in the daily practice,
      however, the disturbances of perception of a mild degree lead to cognitive
      distortions, and they make the recognition of the depression significantly more
      difficult. PURPOSE: To review several systems of diagnostic criteria, five
      developed in Europe, ten in the United Kingdom, five in the United States and
      five other diagnostic systems with respect to the kind of significance they
      ascribe to the disturbances of perception in the presence of depression. RESULTS:
      The author establishes that the diagnostic systems examined in case of the
      patients suffering from depression ascribe different significances to the
      disturbances of perception despite the fact that all depressed patients suffer
      from these symptoms. In case of the 23 examined disturbances of perception, out
      of the 25 systems 20 ascribe significance to fewer than ten symptoms, 11 systems
      ascribe significance to five or fewer symptoms. In the process of the
      simplification of the diagnostic systems these symptoms do not obtain emphasis,
      which makes the establishment of the accurate diagnosis difficult. The author
      emphasizes that in the background of disturbances of perception the detection of
      the misshapen reality hides, from which the patients suffer the most. Out of the
      examined diagnostic systems the European and the complex diagnostic systems
      ascribe a more considerable emphasis to the disturbances of perception. In
      Kielholz's system there are 14, while in the CODE system there are 19 kinds of
      disturbances of perception. CONCLUSION: The author establishes that the
      disturbances of perception and the symptoms developed by the consequences of the
      disturbances of perception have a greater significance in patients suffering from
      depressive disorders than it is known in the common knowledge. In fact most of
      the psychiatric signs and symptoms may be attributable to some kind of
      disturbance of perception. Out of the examined diagnostic systems Paul Kielholz's
      and Thomas Ban's complex diagnostic system, the CODE-DD takes the significance of
      the disturbances of perception into consideration in the largest degree. It is
      necessary to keep in mind that patients suffering from depression with
      disturbances of perception also present have difficulty in recovery. In the
      process of the simplification of the diagnostic systems these symptoms may evade
      the doctors' attention making the recognition of the illness more difficult and
      weaken the efficiency of the therapy. It would be justified to indicate the
      disturbances of perception as a diagnostic criterion in the ICD-11 and in the DSM
      V among the illnesses related to depression. Paying attention to the disturbances
      of perception may transform the system of psychiatric classifications and the
      research of psychiatric illnesses not only in case of affective disorders but
      also in case of psychoses. Especially the genetic research concerning the
      disturbances of perception may support the objective judgement of the psychiatric
      disorders, its biological tenability could stabilize the situation of psychiatry
      among medical sciences.

PMID- 20150661
TI  - [The role of childhood abuse in adult suicidal behaviour].
AB  - In our present study we have analysed the influence of childhood abuse on
      affective temperament-types and Gotland Male Depression Scale scores in 150
      nonviolent suicide attempters. Our findings confirm previous Hungarian and
      international data concerning the connection of suicidal behaviour and
      psychiatric disorders, undesirable psychosocial circumstances and negative life
      events. Moreover, our study provides new results regarding the strong association
      of the affective temperament types, male type of depression, seriously traumatic
      early life events and furthermore their predisposing role in connection with
      suicidal behaviour. Suicide attempters, experiencing physical and/or sexual abuse
      in their childhood showed significantly higher total scores (p<0.05) on
      cyclothymic and irritable temperament subscales. The Gotland Male Depressive
      syndrome was equally very common and equally serious both in males and females
      who made a nonviolent suicide attempt. However, regardless of gender, it was
      significantly more severe (p<0.01) among those who were victims of both physical
      and sexual childhood abuse.

PMID- 20150663
TI  - [Successful quetiapine therapy in psychotic patients with mood elevation].
AB  - Antipsychotics have been used in the therapy of schizophrenia and bipolar
      disorder and several second generation antipsychotics (SGA) are already available
      in Hungary. The clinical trials' results are confusing in regarding the
      differences in the efficacy of the SGA's, but the differences in their side
      effects are clear. Considering its most important side-effects, such as
      extrapyramidal symptoms, weight gain, metabolic syndrome and prolactin level
      elevation, quetiapine has a fairly good side effect profile, and can therefore be
      recommended especially in case of bipolar patients who are highly sensitive
      towards side effects.. In our case-report, we present four patients who were
      successfully treated with quetiapine for their psychotic mood elevation.

PMID- 20150662
TI  - Early experience with Suboxone maintenance therapy in Hungary.
AB  - BACKGROUND: Suboxone (Buprenorphine/naloxone) is a novel drug used in opiate
      substitution therapy. In Hungary, it was introduced in November 2007. Suboxone is
      a product for sublingual administration containing the partial mu-receptor
      agonist buprenorphine and antagonist naloxone in a 4:1 ratio. OBJECTIVE:
      Objectives of our study were to monitor and evaluate the effects of Suboxone
      treatment. METHOD: 6 outpatient centers participated in the study, 3 from
      Budapest and 3 from smaller cities in Hungary. At these centers, all patients
      entering Suboxone maintenance therapy between November 2007 and March 2008,
      altogether 80 persons (55 males, 35 females, mean age = 30.2 years, SD=5.48) were
      included in the study sample. During the 6-month period of treatment, data were
      collected 4 times; when entering treatment, 1 month, 3 months, and 6 months after
      entering treatment. Applied measures were the Addiction Severity Index, SCID-I,
      SCID-II, Hamilton Depression Scale, Hamilton Anxiety Scale, STAI-S State Anxiety
      Inventory, Beck Depression Inventory, Heroin Craving Questionnaire, WHO Well
      being Inventory, Perceived Stress Scale, ADHD retrospective questionnaire, TCI
      short version, and Ways of Coping questionnaire. RESULTS: Nearly fourth of the
      altogether 80 heroin dependent patients (18 persons, 22.5%) dropped out of
      treatment during the first month (the majority, 12 persons [15%] during the first
      week) or chose methadone substitution instead. Following this period however,
      dropout rate decreased and the six-month treatment period was completed by 32
      patients (40%). During the first month of treatment significant positive changes
      were experienced in all studied psychological and behavioral dimensions that
      proved to be stabile throughout the studied period. CONCLUSIONS: According to the
      early experience with Suboxone treatment, it is a well tolerable and successfully
      applicable drug in the substitution therapy of opiate addicts. A critical phase
      seems to be the first one or two weeks of treatment. Dropout rate is high during
      this early period, while after a successful conversion clients presumably remain
      in therapy for a long period. At the beginning of administration special emphasis
      must be put on informing patients, especially concerning withdrawal symptoms that
      might be present during the first week, which highly contributes to better
      retention in treatment.

PMID- 20150664
TI  - Automatic detection of large dense-core vesicles in secretory cells and
      statistical analysis of their intracellular distribution.
AB  - Analyzing the morphological appearance and the spatial distribution of large
      dense-core vesicles (granules) in the cell cytoplasm is central to the
      understanding of regulated exocytosis. This paper is concerned with the automatic
      detection of granules and the statistical analysis of their spatial locations in
      different cell groups. We model the locations of granules of a given cell as a
      realization of a finite spatial point process and the point patterns associated
      with the cell groups as replicated point patterns of different spatial point
      processes. First, an algorithm to segment the granules using electron microscopy
      images is proposed. Second, the relative locations of the granules with respect
      to the plasma membrane are characterized by two functional descriptors: the
      empirical cumulative distribution function of the distances from the granules to
      the plasma membrane and the density of granules within a given distance to the
      plasma membrane. The descriptors of the different cells for each group are
      compared using bootstrap procedures. Our results show that these descriptors and
      the testing procedure allow discriminating between control and treated cells. The
      application of these novel tools to studies of secretion should help in the
      analysis of diseases associated with dysfunctional secretion, such as diabetes.

PMID- 20150665
TI  - BioExtract server--an integrated workflow-enabling system to access and analyze
      heterogeneous, distributed biomolecular data.
AB  - Many in silico investigations in bioinformatics require access to multiple,
      distributed data sources and analytic tools. The requisite data sources may
      include large public data repositories, community databases, and project
      databases for use in domain-specific research. Different data sources frequently
      utilize distinct query languages and return results in unique formats, and
      therefore researchers must either rely upon a small number of primary data
      sources or become familiar with multiple query languages and formats. Similarly,
      the associated analytic tools often require specific input formats and produce
      unique outputs which make it difficult to utilize the output from one tool as
      input to another. The BioExtract Server (http://bioextract.org) is a Web-based
      data integration application designed to consolidate, analyze, and serve data
      from heterogeneous biomolecular databases in the form of a mash-up. The basic
      operations of the BioExtract Server allow researchers, via their Web browsers, to
      specify data sources, flexibly query data sources, apply analytic tools, download
      result sets, and store query results for later reuse. As a researcher works with
      the system, their "steps" are saved in the background. At any time, these steps
      can be preserved long-term as a workflow simply by providing a workflow name and
      description.

PMID- 20150666
TI  - Feature selection for gene expression using model-based entropy.
AB  - Gene expression data usually contain a large number of genes but a small number
      of samples. Feature selection for gene expression data aims at finding a set of
      genes that best discriminate biological samples of different types. Using machine
      learning techniques, traditional gene selection based on empirical mutual
      information suffers the data sparseness issue due to the small number of samples.
      To overcome the sparseness issue, we propose a model-based approach to estimate
      the entropy of class variables on the model, instead of on the data themselves.
      Here, we use multivariate normal distributions to fit the data, because
      multivariate normal distributions have maximum entropy among all real-valued
      distributions with a specified mean and standard deviation and are widely used to
      approximate various distributions. Given that the data follow a multivariate
      normal distribution, since the conditional distribution of class variables given
      the selected features is a normal distribution, its entropy can be computed with
      the log-determinant of its covariance matrix. Because of the large number of
      genes, the computation of all possible log-determinants is not efficient. We
      propose several algorithms to largely reduce the computational cost. The
      experiments on seven gene data sets and the comparison with other five approaches
      show the accuracy of the multivariate Gaussian generative model for feature
      selection, and the efficiency of our algorithms.

PMID- 20150667
TI  - Heuristic Bayesian segmentation for discovery of coexpressed genes within genomic
      regions.
AB  - Segmentation aims to separate homogeneous areas from the sequential data, and
      plays a central role in data mining. It has applications ranging from finance to
      molecular biology, where bioinformatics tasks such as genome data analysis are
      active application fields. In this paper, we present a novel application of
      segmentation in locating genomic regions with coexpressed genes. We aim at
      automated discovery of such regions without requirement for user-given
      parameters. In order to perform the segmentation within a reasonable time, we use
      heuristics. Most of the heuristic segmentation algorithms require some decision
      on the number of segments. This is usually accomplished by using asymptotic model
      selection methods like the Bayesian information criterion. Such methods are based
      on some simplification, which can limit their usage. In this paper, we propose a
      Bayesian model selection to choose the most proper result from heuristic
      segmentation. Our Bayesian model presents a simple prior for the segmentation
      solutions with various segment numbers and a modified Dirichlet prior for
      modeling multinomial data. We show with various artificial data sets in our
      benchmark system that our model selection criterion has the best overall
      performance. The application of our method in yeast cell-cycle gene expression
      data reveals potential active and passive regions of the genome.

PMID- 20150668
TI  - Data-fusion in clustering microarray data: balancing discovery and
      interpretability.
AB  - While clustering genes remains one of the most popular exploratory tools for
      expression data, it often results in a highly variable and biologically
      uninformative clusters. This paper explores a data fusion approach to clustering
      microarray data. Our method, which combined expression data and Gene Ontology
      (GO)-derived information, is applied on a real data set to perform genome-wide
      clustering. A set of novel tools is proposed to validate the clustering results
      and pick a fair value of infusion coefficient. These tools measure stability,
      biological relevance, and distance from the expression-only clustering solution.
      Our results indicate that a data-fusion clustering leads to more stable,
      biologically relevant clusters that are still representative of the experimental
      data.

PMID- 20150669
TI  - Integrating data clustering and visualization for the analysis of 3D gene
      expression data.
AB  - The recent development of methods for extracting precise measurements of spatial
      gene expression patterns from three-dimensional (3D) image data opens the way for
      new analyses of the complex gene regulatory networks controlling animal
      development. We present an integrated visualization and analysis framework that
      supports user-guided data clustering to aid exploration of these new complex data
      sets. The interplay of data visualization and clustering-based data
      classification leads to improved visualization and enables a more detailed
      analysis than previously possible. We discuss 1) the integration of data
      clustering and visualization into one framework, 2) the application of data
      clustering to 3D gene expression data, 3) the evaluation of the number of
      clusters k in the context of 3D gene expression clustering, and 4) the
      improvement of overall analysis quality via dedicated postprocessing of
      clustering results based on visualization. We discuss the use of this framework
      to objectively define spatial pattern boundaries and temporal profiles of genes
      and to analyze how mRNA patterns are controlled by their regulatory transcription
      factors.

PMID- 20150670
TI  - Multidimensional profiling of cell surface proteins and nuclear markers.
AB  - Cell membrane proteins play an important role in tissue architecture and cell
      cell communication. We hypothesize that segmentation and multidimensional
      characterization of the distribution of cell membrane proteins, on a cell-by-cell
      basis, enable improved classification of treatment groups and identify important
      characteristics that can otherwise be hidden. We have developed a series of
      computational steps to 1) delineate cell membrane protein signals and associate
      them with a specific nucleus; 2) compute a coupled representation of the
      multiplexed DNA content with membrane proteins; 3) rank computed features
      associated with such a multidimensional representation; 4) visualize selected
      features for comparative evaluation through heatmaps; and 5) discriminate between
      treatment groups in an optimal fashion. The novelty of our method is in the
      segmentation of the membrane signal and the multidimensional representation of
      phenotypic signature on a cell-by-cell basis. To test the utility of this method,
      the proposed computational steps were applied to images of cells that have been
      irradiated with different radiation qualities in the presence and absence of
      other small molecules. These samples are labeled for their DNA content and E
      cadherin membrane proteins. We demonstrate that multidimensional representations
      of cell-by-cell phenotypes improve predictive and visualization capabilities
      among different treatment groups, and identify hidden variables.

PMID- 20150671
TI  - Predicting novel human gene ontology annotations using semantic analysis.
AB  - The correct interpretation of many molecular biology experiments depends in an
      essential way on the accuracy and consistency of the existing annotation
      databases. Such databases are meant to act as repositories for our biological
      knowledge as we acquire and refine it. Hence, by definition, they are incomplete
      at any given time. In this paper, we describe a technique that improves our
      previous method for predicting novel GO annotations by extracting implicit
      semantic relationships between genes and functions. In this work, we use a vector
      space model and a number of weighting schemes in addition to our previous latent
      semantic indexing approach. The technique described here is able to take into
      consideration the hierarchical structure of the Gene Ontology (GO) and can weight
      differently GO terms situated at different depths. The prediction abilities of 15
      different weighting schemes are compared and evaluated. Nine such schemes were
      previously used in other problem domains, while six of them are introduced in
      this paper. The best weighting scheme was a novel scheme, n2tn. Out of the top 50
      functional annotations predicted using this weighting scheme, we found support in
      the literature for 84 percent of them, while 6 percent of the predictions were
      contradicted by the existing literature. For the remaining 10 percent, we did not
      find any relevant publications to confirm or contradict the predictions. The n2tn
      weighting scheme also outperformed the simple binary scheme used in our previous
      approach.

PMID- 20150672
TI  - Sparse support vector machines with Lp penalty for biomarker identification.
AB  - The development of high-throughput technology has generated a massive amount of
      high-dimensional data, and many of them are of discrete type. Robust and
      efficient learning algorithms such as LASSO [1] are required for feature
      selection and overfitting control. However, most feature selection algorithms are
      only applicable to the continuous data type. In this paper, we propose a novel
      method for sparse support vector machines (SVMs) with L_(p) (p < 1)
      regularization. Efficient algorithms (LpSVM) are developed for learning the
      classifier that is applicable to high-dimensional data sets with both discrete
      and continuous data types. The regularization parameters are estimated through
      maximizing the area under the ROC curve (AUC) of the cross-validation data.
      Experimental results on protein sequence and SNP data attest to the accuracy,
      sparsity, and efficiency of the proposed algorithm. Biomarkers identified with
      our methods are compared with those from other methods in the literature. The
      software package in Matlab is available upon request.

PMID- 20150673
TI  - A multiple-filter-multiple-wrapper approach to gene selection and microarray data
      classification.
AB  - Filters and wrappers are two prevailing approaches for gene selection in
      microarray data analysis. Filters make use of statistical properties of each gene
      to represent its discriminating power between different classes. The computation
      is fast but the predictions are inaccurate. Wrappers make use of a chosen
      classifier to select genes by maximizing classification accuracy, but the
      computation burden is formidable. Filters and wrappers have been combined in
      previous studies to maximize the classification accuracy for a chosen classifier
      with respect to a filtered set of genes. The drawback of this single-filter
      single-wrapper (SFSW) approach is that the classification accuracy is dependent
      on the choice of specific filter and wrapper. In this paper, a multiple-filter
      multiple-wrapper (MFMW) approach is proposed that makes use of multiple filters
      and multiple wrappers to improve the accuracy and robustness of the
      classification, and to identify potential biomarker genes. Experiments based on
      six benchmark data sets show that the MFMW approach outperforms SFSW models
      (generated by all combinations of filters and wrappers used in the corresponding
      MFMW model) in all cases and for all six data sets. Some of MFMW-selected genes
      have been confirmed to be biomarkers or contribute to the development of
      particular cancers by other studies.

PMID- 20150674
TI  - A trade-off between sample complexity and computational complexity in learning
      Boolean networks from time-series data.
AB  - A key problem in molecular biology is to infer regulatory relationships between
      genes from expression data. This paper studies a simplified model of such
      inference problems in which one or more Boolean variables, modeling, for example,
      the expression levels of genes, each depend deterministically on a small but
      unknown subset of a large number of Boolean input variables. Our model assumes
      that the expression data comprises a time series, in which successive samples may
      be correlated. We provide bounds on the expected amount of data needed to infer
      the correct relationships between output and input variables. These bounds
      improve and generalize previous results for Boolean network inference and
      continuous-time switching network inference. Although the computational problem
      is intractable in general, we describe a fixed-parameter tractable algorithm that
      is guaranteed to provide at least a partial solution to the problem. Most
      interestingly, both the sample complexity and computational complexity of the
      problem depend on the strength of correlations between successive samples in the
      time series but in opposing ways. Uncorrelated samples minimize the total number
      of samples needed while maximizing computational complexity; a strong correlation
      between successive samples has the opposite effect. This observation has
      implications for the design of experiments for measuring gene expression.

PMID- 20150675
TI  - Efficient peak-labeling algorithms for whole-sample mass spectrometry proteomics.
AB  - Whole-sample mass spectrometry (MS) proteomics allows for a parallel measurement
      of hundreds of proteins present in a variety of biospecimens. Unfortunately, the
      association between MS signals and these proteins is not straightforward. The
      need to interpret mass spectra demands the development of methods for accurate
      labeling of ion species in such profiles. To aid this process, we have developed
      a new peak-labeling procedure for associating protein and peptide labels with
      peaks. This computational method builds upon characteristics of proteins expected
      to be in the sample, such as the amino sequence, mass weight, and expected
      concentration within the sample. A new probabilistic score that incorporates this
      information is proposed. We evaluate and demonstrate our method's ability to
      label peaks first on simulated MS spectra and then on MS spectra from human serum
      with a spiked-in calibration mixture.

PMID- 20150676
TI  - Exploratory consensus of hierarchical clusterings for melanoma and breast cancer.
AB  - Finding subtypes of heterogeneous diseases is the biggest challenge in the area
      of biology. Often, clustering is used to provide a hypothesis for the subtypes of
      a heterogeneous disease. However, there are usually discrepancies between the
      clusterings produced by different algorithms. This work introduces a simple
      method which provides the most consistent clusters across three different
      clustering algorithms for a melanoma and a breast cancer data set. The method is
      validated by showing that the Silhouette, Dunne's and Davies-Bouldin's cluster
      validation indices are better for the proposed algorithm than those obtained by k
      means and another consensus clustering algorithm. The hypotheses of the consensus
      clusters on both the data sets are corroborated by clear genetic markers and 100
      percent classification accuracy. In Bittner et al.'s melanoma data set, a
      previously hypothesized primary cluster is recognized as the largest consensus
      cluster and a new partition of this cluster into two subclusters is proposed. In
      van't Veer et al.'s breast cancer data set, previously proposed "basal" and
      "luminal A" subtypes are clearly recognized as the two predominant clusters.
      Furthermore, a new hypothesis is provided about the existence of two subgroups
      within the "basal" subtype in this data set. The clusters of van't Veer's data
      set is also validated by high classification accuracy obtained in the data set of
      van de Vijver et al.

PMID- 20150677
TI  - Identification of regulatory modules in time series gene expression data using a
      linear time biclustering algorithm.
AB  - Although most biclustering formulations are NP-hard, in time series expression
      data analysis, it is reasonable to restrict the problem to the identification of
      maximal biclusters with contiguous columns, which correspond to coherent
      expression patterns shared by a group of genes in consecutive time points. This
      restriction leads to a tractable problem. We propose an algorithm that finds and
      reports all maximal contiguous column coherent biclusters in time linear in the
      size of the expression matrix. The linear time complexity of CCC-Biclustering
      relies on the use of a discretized matrix and efficient string processing
      techniques based on suffix trees. We also propose a method for ranking biclusters
      based on their statistical significance and a methodology for filtering highly
      overlapping and, therefore, redundant biclusters. We report results in synthetic
      and real data showing the effectiveness of the approach and its relevance in the
      discovery of regulatory modules. Results obtained using the transcriptomic
      expression patterns occurring in Saccharomyces cerevisiae in response to heat
      stress show not only the ability of the proposed methodology to extract relevant
      information compatible with documented biological knowledge but also the utility
      of using this algorithm in the study of other environmental stresses and of
      regulatory modules in general.

PMID- 20150678
TI  - Incomplete lineage sorting: consistent phylogeny estimation from multiple loci.
AB  - We introduce a simple computationally efficient algorithm for reconstructing
      phylogenies from multiple gene trees in the presence of incomplete lineage
      sorting, that is, when the topology of the gene trees may differ from that of the
      species tree. We show that our technique is statistically consistent under
      standard stochastic assumptions, that is, it returns the correct tree given
      sufficiently many unlinked loci. We also show that it can tolerate moderate
      estimation errors.

PMID- 20150679
TI  - On the importance of comprehensible classification models for protein function
      prediction.
AB  - The literature on protein function prediction is currently dominated by works
      aimed at maximizing predictive accuracy, ignoring the important issues of
      validation and interpretation of discovered knowledge, which can lead to new
      insights and hypotheses that are biologically meaningful and advance the
      understanding of protein functions by biologists. The overall goal of this paper
      is to critically evaluate this approach, offering a refreshing new perspective on
      this issue, focusing not only on predictive accuracy but also on the
      comprehensibility of the induced protein function prediction models. More
      specifically, this paper aims to offer two main contributions to the area of
      protein function prediction. First, it presents the case for discovering
      comprehensible protein function prediction models from data, discussing in detail
      the advantages of such models, namely, increasing the confidence of the biologist
      in the system's predictions, leading to new insights about the data and the
      formulation of new biological hypotheses, and detecting errors in the data.
      Second, it presents a critical review of the pros and cons of several different
      knowledge representations that can be used in order to support the discovery of
      comprehensible protein function prediction models.

PMID- 20150680
TI  - Approximate maximum parsimony and ancestral maximum likelihood.
AB  - We explore the maximum parsimony (MP) and ancestral maximum likelihood (AML)
      criteria in phylogenetic tree reconstruction. Both problems are NP-hard, so we
      seek approximate solutions. We formulate the two problems as Steiner tree
      problems under appropriate distances. The gist of our approach is the succinct
      characterization of Steiner trees for a small number of leaves for the two
      distances. This enables the use of known Steiner tree approximation algorithms.
      The approach leads to a 16/9 approximation ratio for AML and asymptotically to a
      1.55 approximation ratio for MP.

PMID- 20150681
TI  - Comparison of anatomic coordinate systems with rigid multi-resolution 3D
      registration for the reproducible positioning of analysis volumes of interest in
      QCT.
AB  - In this study we compared two approaches that have recently been used to minimize
      precision errors in 3D quantitative computed tomography (QCT) images of the hip
      and the spine in order to optimize the detection of longitudinal changes in bone
      mineral density (BMD). In 30 subjects we obtained baseline and 1 year follow-up
      3D CT scans of the proximal femur and the spine. QCT analysis was applied to a
      variety of volumes of interest (VOIs) automatically positioned relative to
      anatomic coordinate systems (ACS). In the first approach (A1) baseline and follow
      up scans were analyzed independently. In the second approach (A2) a 3D versor
      based rigid intensity registration method was applied to match baseline and
      follow-up images, and the baseline ACS was mapped on the follow-up image using
      the registration transformation. Afterwards, the analysis VOIs were again
      independently calculated for baseline and follow-up images. There were no
      significant differences of percent BMD changes between baseline and follow-up
      images between A1 and A2 for any of the VOIs investigated. With advanced image
      processing methods a time-consuming 3D registration between baseline and follow
      up images before the analysis does not improve analysis precision compared to the
      use of anatomical coordinate systems.

PMID- 20150682
TI  - Intensity- and energy-modulated electron radiotherapy by means of an xMLC for
      head and neck shallow tumors.
AB  - The purpose of this paper is to assess the feasibility of delivering intensity-
      and energy-modulated electron radiation treatment (MERT) by a photon multileaf
      collimator (xMLC) and to evaluate the improvements obtained in shallow head and
      neck (HN) tumors. Four HN patient cases covering different clinical situations
      were planned by MERT, which used an in-house treatment planning system that
      utilized Monte Carlo dose calculation. The cases included one oronasal, two
      parotid and one middle ear tumors. The resulting dose-volume histograms were
      compared with those obtained from conventional photon and electron treatment
      techniques in our clinic, which included IMRT, electron beam and mixed beams,
      most of them using fixed-thickness bolus. Experimental verification was performed
      with plane-parallel ionization chambers for absolute dose verification, and a PTW
      ionization chamber array and radiochromic film for relative dosimetry. A MC-based
      treatment planning system for target with compromised volumes in depth and
      laterally has been validated. A quality assurance protocol for individual MERT
      plans was launched. Relative MC dose distributions showed a high agreement with
      film measurements and absolute ion chamber dose measurements performed at a
      reference point agreed with MC calculations within 2% in all cases. Clinically
      acceptable PTV coverage and organ-at-risk sparing were achieved by using the
      proposed MERT approach. MERT treatment plans, based on delivery of intensity
      modulated electron beam using the xMLC, for superficial head and neck tumors,
      demonstrated comparable or improved PTV dose homogeneity with significantly lower
      dose to normal tissues. The clinical implementation of this technique will be
      able to offer a viable alternative for the treatment of shallow head and neck
      tumors.

PMID- 20150683
TI  - Noise and signal properties in PSF-based fully 3D PET image reconstruction: an
      experimental evaluation.
AB  - The addition of accurate system modeling in PET image reconstruction results in
      images with distinct noise texture and characteristics. In particular, the
      incorporation of point spread functions (PSF) into the system model has been
      shown to visually reduce image noise, but the noise properties have not been
      thoroughly studied. This work offers a systematic evaluation of noise and signal
      properties in different combinations of reconstruction methods and parameters. We
      evaluate two fully 3D PET reconstruction algorithms: (1) OSEM with exact scanner
      line of response modeled (OSEM+LOR), (2) OSEM with line of response and a
      measured point spread function incorporated (OSEM+LOR+PSF), in combination with
      the effects of four post-reconstruction filtering parameters and 1-10 iterations,
      representing a range of clinically acceptable settings. We used a modified NEMA
      image quality (IQ) phantom, which was filled with 68Ge and consisted of six hot
      spheres of different sizes with a target/background ratio of 4:1. The phantom was
      scanned 50 times in 3D mode on a clinical system to provide independent noise
      realizations. Data were reconstructed with OSEM+LOR and OSEM+LOR+PSF using
      different reconstruction parameters, and our implementations of the algorithms
      match the vendor's product algorithms. With access to multiple realizations,
      background noise characteristics were quantified with four metrics. Image
      roughness and the standard deviation image measured the pixel-to-pixel variation;
      background variability and ensemble noise quantified the region-to-region
      variation. Image roughness is the image noise perceived when viewing an
      individual image. At matched iterations, the addition of PSF leads to images with
      less noise defined as image roughness (reduced by 35% for unfiltered data) and as
      the standard deviation image, while it has no effect on background variability or
      ensemble noise. In terms of signal to noise performance, PSF-based reconstruction
      has a 7% improvement in contrast recovery at matched ensemble noise levels and
      20% improvement of quantitation SNR in unfiltered data. In addition, the
      relations between different metrics are studied. A linear correlation is observed
      between background variability and ensemble noise for all different combinations
      of reconstruction methods and parameters, suggesting that background variability
      is a reasonable surrogate for ensemble noise when multiple realizations of scans
      are not available.

PMID- 20150684
TI  - Monitoring T2 and ADC at 9.4 T following fractionated external beam radiation
      therapy in a mouse model.
AB  - The purpose of this study is to investigate the response of transverse relaxation
      time (T2) and apparent diffusion coefficient (ADC) in human glioma tumor
      xenografts during and after fractionated radiotherapy. Tumor-bearing mice were
      divided into four treatment groups (n=6 per group) that received a total dose of
      800 cGy of 200 kVp x-rays, given over two or three fractions, with a fraction
      spacing of either 24 or 72 h. A fifth treatment group received 800 cGy in a
      single fraction, and a sixth group of mice served as an untreated control. All
      mice were scanned pretreatment, before each fraction and at multiple points after
      treatment using a 9.4 T magnetic resonance imaging (MRI) system. Quantitative T2
      and ADC maps were produced. All treated groups showed an increase in mean tumor
      ADC, though the time for this response to reach a maximum and return toward
      baseline was delayed in the fractionated groups. The highest ADC was measured 7
      days after the final fraction of treatment for all groups. There were no
      significant differences in the maximum measured change in ADC between any of the
      treated groups, with the average measured maximum value being 20.5% above
      baseline. After treatment, all groups showed an increase in mean tumor T2, with
      the average measured maximum T2 being 4.7% above baseline. This increase was
      followed by a transition to mean T2 values below baseline values, with the
      average measured tumor T2 being 92.4% of the pretreatment value. The transition
      between elevated and depressed T2 values was delayed in the cases of fractionated
      therapies and occurred between 3.6 and 7.3 days after the last fraction of
      treatment. These results further the understanding of the temporal evolution of
      T2 and ADC during fractionated radiotherapy and support their potential use as
      time-sensitive biomarkers for tumor response.

PMID- 20150685
TI  - Vortex formation and recirculation zones in left anterior descending artery
      stenoses: computational fluid dynamics analysis.
AB  - Flow patterns may affect the potential of thrombus formation following plaque
      rupture. Computational fluid dynamics (CFD) were employed to assess hemodynamic
      conditions, and particularly flow recirculation and vortex formation in
      reconstructed arterial models associated with ST-elevation myocardial infraction
      (STEMI) or stable coronary stenosis (SCS) in the left anterior descending
      coronary artery (LAD). Results indicate that in the arterial models associated
      with STEMI, a 50% diameter stenosis immediately before or after a bifurcation
      creates a recirculation zone and vortex formation at the orifice of the
      bifurcation branch, for most of the cardiac cycle, thus allowing the creation of
      stagnating flow. These flow patterns are not seen in the SCS model with an
      identical stenosis. Post-stenotic recirculation in the presence of a 90% stenosis
      was evident at both the STEMI and SCS models. The presence of 90% diameter
      stenosis resulted in flow reduction in the LAD of 51.5% and 35.9% in the STEMI
      models and 37.6% in the SCS model, for a 10 mmHg pressure drop. CFD simulations
      in a reconstructed model of stenotic LAD segments indicate that specific anatomic
      characteristics create zones of vortices and flow recirculation that promote
      thrombus formation and potentially myocardial infarction.

PMID- 20150686
TI  - Comparison of two types of adult phantoms in terms of organ doses from diagnostic
      CT procedures.
AB  - The rapidly increasing number of diagnostic computed tomography (CT) procedures
      in the recent decades has spurred heightened concern over the potential risk to
      patients. Although an accurate organ dose assessment tool has now become highly
      desirable, existing software packages depend on stylized computational phantoms
      that were originally developed more than 40 years ago, exhibiting very large
      discrepancies when compared with phantoms that are anatomically realistic.
      However, past comparative studies did not focus on CT protocols for adult
      patients. This study was designed to quantitatively compare two types of
      phantoms, the stylized phantoms and a pair of recently developed RPI-adult male
      and adult female (RPI-AM and RPI-AF) phantoms, for various CT scanning protocols
      involving the chest, abdomen-pelvis and chest-abdomen-pelvis. Organ doses were
      based on Monte Carlo simulations using the MCNPX code and a detailed CT scanner
      model for the GE LightSpeed 16. Results are presented as ratios of organ doses
      from the stylized phantoms to those from the RPI phantoms. It is found that, for
      most organs contained in the scan volume, the ratios were within the range of
      0.75-1.16. However, the stomach doses are significantly different and the ratio
      is found to be up to 1.86 in male phantoms and 2.29 in the female phantoms due to
      the anatomical differences between the two types of phantoms. Organs that lie
      near a scan boundary also exhibit a significant relative difference in organ
      doses between the two types of phantoms. This study concludes that, due to
      relatively low x-ray energies, CT doses are very sensitive to organ shape, size
      and position, and thus anatomically realistic phantoms should be used to avoid
      the dose uncertainties caused by the lack of anatomical realism. The new
      phantoms, such as the RPI-AM and AF phantoms that are designed using advanced
      surface meshes, are deformable and will make it possible to match the anatomy of
      a specific patient leading to further improvement in dose and risk assessments
      for patients undergoing CT examinations.

PMID- 20150688
TI  - Real-time ischemic condition monitoring in normoglycemic and hyperglycemic rats.
AB  - An increase in excitotoxic amino acid glutamate (GLU) concentration associated
      with neuronal damage might be the cause of the ischemic damage observed in stroke
      patients suffering from hyperglycemia. However, the effect has never been
      investigated by real-time in vivo monitoring. Therefore, this study examined the
      effects of the functional responses of ischemia-evoked electroencephalography
      (EEG), cerebral blood flow (%CBF) and DeltaGLU in hyperglycemia through real-time
      in vivo monitoring. Five Sprague-Dawley rats were treated with streptozocin
      (hyperglycemia) and five normal rats were used as the controls. Global ischemia
      was induced using an 11-vessel occlusion model. The experimental protocols
      consisting of 10 min pre-ischemic, 10 min ischemic and 40 min reperfusion periods
      were applied to both groups. Under these conditions, the responses of the
      ischemia-evoked EEG, %CBF and DeltaGLU were monitored in real time. The EEG
      showed flat patterns during ischemia followed by poor recovery during
      reperfusion. The peak reperfusion %CBF was decreased significantly in the
      hyperglycemia group compared to the control group (p < 0.05, n = 5). The
      extracellular DeltaGLU releases increased significantly during ischemia (p <
      0.0001, n = 5) and reperfusion (p < 0.001, n = 5) in the hyperglycemia group
      compared to the control group. The decrease in reperfusion %CBF during short-term
      hyperglycemia might be related to the increased plasma osmolality, decreased
      adenosine levels and swollen endothelial cells with decreased vascular luminal
      diameters under hyperglycemic conditions. And, the increase in DeltaGLU during
      short-term hyperglycemia might be related to the neurotoxic effects of the high
      extracellular concentrations of DeltaGLU and the inhibition of GLU uptake.

PMID- 20150689
TI  - Tracheal sound parameters of respiratory cycle phases show differences between
      flow-limited and normal breathing during sleep.
AB  - The objective of the present work was to develop new computational parameters to
      examine the characteristics of respiratory cycle phases from the tracheal
      breathing sound signal during sleep. Tracheal sound data from 14 patients (10
      males and 4 females) were examined. From each patient, a 10 min long section of
      normal and a 10 min section of flow-limited breathing during sleep were analysed.
      The computationally determined proportional durations of the respiratory phases
      were first investigated. Moreover, the phase durations and breathing sound
      amplitude levels were used to calculate the area under the breathing sound
      envelope signal during inspiration and expiration phases. An inspiratory sound
      index was then developed to provide the percentage of this type of area during
      the inspiratory phase with respect to the combined area of inspiratory and
      expiratory phases. The proportional duration of the inspiratory phase showed
      statistically significantly higher values during flow-limited breathing than
      during normal breathing and inspiratory pause displayed an opposite difference.
      The inspiratory sound index showed statistically significantly higher values
      during flow-limited breathing than during normal breathing. The presented novel
      computational parameters could contribute to the examination of sleep-disordered
      breathing or as a screening tool.

PMID- 20150690
TI  - Ammonia volatilisation in waste stabilisation ponds: a cascade of
      misinterpretations?
AB  - Ammonia volatilisation has generally been reported as, or assumed to be, the main
      nitrogen removal mechanism in waste stabilisation ponds (WSP). Nitrogen removal
      via ammonia volatilisation is based on two observations: (a) in-pond pH values
      can reach high values (>9, even >10), so increasing the proportion of the total
      ammonia present as the un-ionized form or free ammonia (NH(3)); and (b) in-pond
      temperatures can also be high, so improving the mass transfer rate of free
      ammonia to the atmosphere. Consequently, one of the most widely accepted models
      for ammonia removal in WSP is that reported by Pano & Middlebrooks in 1982, which
      was developed to reflect the occurrence of these two observations. This work
      reports how simple mathematical models for ammonia volatilisation in WSP, in
      spite of the possibility of their giving good predictions, may not accurately
      describe the main pathways and mechanisms involved in ammonia removal in WSP.

PMID- 20150687
TI  - Polymer gel dosimetry.
AB  - Polymer gel dosimeters are fabricated from radiation sensitive chemicals which,
      upon irradiation, polymerize as a function of the absorbed radiation dose. These
      gel dosimeters, with the capacity to uniquely record the radiation dose
      distribution in three-dimensions (3D), have specific advantages when compared to
      one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters,
      such as film. These advantages are particularly significant in dosimetry
      situations where steep dose gradients exist such as in intensity-modulated
      radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters
      also have specific advantages for brachytherapy dosimetry. Potential dosimetry
      applications include those for low-energy x-rays, high-linear energy transfer
      (LET) and proton therapy, radionuclide and boron capture neutron therapy
      dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with
      properties that may be modified depending on the application. The 3D radiation
      dose distribution in polymer gel dosimeters may be imaged using magnetic
      resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT
      or ultrasound. The fundamental science underpinning polymer gel dosimetry is
      reviewed along with the various evaluation techniques. Clinical dosimetry
      applications of polymer gel dosimetry are also presented.

PMID- 20150691
TI  - Waterborne disease in Norway: emphasizing outbreaks in groundwater systems.
AB  - In this study, we compiled and examined available data on waterborne disease
      outbreaks (1984-2007) in Norway, with emphasis on groundwater systems. A total of
      102 waterborne outbreaks and 17,243 disease cases were reported during the period
      1984-2007. The proportion of outbreaks related to groundwater reflected the
      proportion of groundwater works in Norway (40%). The proportion of disease cases
      corresponded to the proportion of persons supplied by groundwater (15%).
      Norovirus was identified as the most important disease causing agent in
      groundwater systems. No clear seasonal correlation was observed for Norovirus
      outbreaks in groundwater, but the largest outbreaks occurred during winter
      season. All outbreaks of campylobacteriosis occurred during March to November,
      with a peak in July-September, which correlates with the occurrence of coliforms
      in Norwegian groundwater in bedrock wells.

PMID- 20150692
TI  - Resistance of nitrifiers inhabiting activated sludge to ciliate grazing.
AB  - We monitored the succession of nitrifiers in a newly opened wastewater treatment
      plant for five weeks. After the first distinct decrease in total nitrogen, we
      began monitoring the appearance, size and number of nitrifying bacteria colonies
      using the fluorescence in situ hybridization (FISH) method. Ammonia oxidizing
      bacteria (AOB) colonies were visualized under green excitation as red, and
      nitrite oxidizing bacteria (NOB) colonies were visualized under blue excitation
      as green. The changes in protozoan community were monitored simultaneously.
      Ciliates were divided into four functional groups: predatory, bacterivorous free
      swimming, bacterivorous crawling, and sessile. The results showed that at the
      time of the first distinct total nitrogen decrease, the mean length of both AOB
      and NOB were relatively low, but the colonies, especially those of nitrite
      oxidizers, were abundant. In time, the distribution of ammonia oxidizer colonies
      shifted towards larger sizes, but their quantity decreased. In the case of
      nitrite oxidizers, a similar trend was noticeable but less pronounced. These
      changes corresponded with an increasing number of crawling bacterivorous ciliates
      dominated by the "scavenger" genus Aspidisca. The increasing size of nitrifier
      colonies may have been due to the growing grazing pressure from crawling
      bacterivorous ciliates. The strong grazing pressure did not negatively affect N
      NH(4)(+) removal effectiveness.

PMID- 20150694
TI  - Removal of mercury from water by multi-walled carbon nanotubes.
AB  - The removal of mercury (Hg(2+)) ions from contaminated water using multiwalled
      carbon nanotubes (MWCNTs) was investigated in this study. Results of the study
      showed that MWCNTs slurry was very efficient in removing as high as 1.0 mg/L of
      Hg(2+) from aqueous solutions via the adsorption mechanism. This removal
      efficiency was found to be a function of the aqueous pH level, dosage of CNTs,
      mixing rate, and contact time. The study showed that the Hg uptake by MWCNTs
      increased to 100% with an increase in pH from pH 4 to 8. The results also showed
      that higher dosage of MWCNTs, showed higher removal of Hg(2+). In a 50 mL water
      sample, 10 mg of MWCNTs was needed to remove all of the 0.1 mg/L of Hg(2+) ions.
      On the other hand, increasing the mixing rate from 50 to 150 rpm improved the
      removal efficiency. The experimental results also showed that mercury adsorption
      by MWCNTs follow a pseudo second-order reaction with a rate (k) of 0.018 and it
      is well described by the Langmuir isotherm model with maximum adsorptive capacity
      (q(max)) of 13.16.

PMID- 20150693
TI  - Copper removal from sludge permeate with ultrafiltration membranes using zeolite,
      bentonite and vermiculite as adsorbents.
AB  - The aim of this work is to examine copper removal from sludge permeate with the
      use of low-cost minerals of Mediterranean origin combined with ultrafiltration
      membranes. The minerals used were zeolite (clinoptilolite), bentonite and
      vermiculite. Activated sludge was enriched with 0.01 N (317.7 ppm) of Cu(II).
      Fixed concentrations of minerals were added to sludge and the pH value was
      adjusted at 5.5. The mixture was agitated for 2 hours at 800 rpm at room
      temperature and was then filtered through a batch ultrafiltration system for 1
      hour. This experiment was repeated, for comparison purposes, with sludge enriched
      with 0.01 N of Cu(II) with no mineral addition. The results showed that
      ultrafiltration membranes with no mineral addition were able to remove a
      significant amount of copper with removal efficiencies ranging from 59.4-78.3%.
      The addition of 10 g/l and 20 g/l of bentonite combined with ultrafiltration
      membranes resulted in removal efficiencies of 94.9% and 99.4% respectively and
      that of 10 g/l and 20 g/l of vermiculite in removal efficiencies of 93.8% and
      96.8%, respectively. The ion exchange capacity of minerals followed the order
      bentonite > vermiculite > zeolite. Furthermore, membrane fouling was
      investigated. The addition of zeolite and bentonite reduced membrane fouling,
      while the addition of vermiculite did not impact on fouling. The use of low-cost
      minerals in combination with ultrafiltration membranes can be employed to treat
      industrial wastewater, resulting in a final effluent with very low copper
      concentrations.

PMID- 20150695
TI  - Sorption and desorption of phosphorus by shale: batch and column studies.
AB  - Constructed wetland systems have gained attention as attractive solutions for
      wastewater treatment. Wetlands are not efficient to treat wastewater with high
      concentrations of phosphorus (P). In order to remove high soluble P loads by
      wetland, sorbent beds can be added prior to the discharge of wastewater into
      wetlands. Sorption by sorbent materials is identified as a method for trapping
      excess P in wastewaters. In the present investigation, shale has been identified
      as a sorbent material for removal of phosphate (PO(4)-P) due to the cost
      effectiveness, stability and possibility of regeneration. The study focuses on
      the removal of PO(4)-P from wastewater using shale and the feasibility of using
      the P-sorbed material as slow-release fertilizer. Phosphorus sorption experiments
      were conducted by using shale (2 mm and 2-4.7 mm). Results indicate that Shale I
      (particle size = 2 mm) showed the highest sorption of PO(4)-P (500 +/- 44 mg kg(
      1)). Breakthrough point was reached within 10 h in columns with flow rates of 2
      and 3 ml min(-1). Lower flow rate of 1 ml min(-1) showed an average residence
      time of about 2 h while columns with a higher flow rate of 3 ml min(-1) showed a
      residence time of about 40 minutes. Variation in flow rate did not influence the
      desorption process. Since very low concentrations of PO(4)-P are released, Shale
      saturated with PO(4)-P may be used as a slow nutrient release source of P or as a
      soil amendment. The sorbent can also be regenerated by removing the sorbed PO(4)
      P by using 0.1 N HCl.

PMID- 20150696
TI  - A parsimonious dynamic model for river water quality assessment.
AB  - Water quality modelling is of crucial importance for the assessment of physical,
      chemical, and biological changes in water bodies. Mathematical approaches to
      water modelling have become more prevalent over recent years. Different model
      types ranging from detailed physical models to simplified conceptual models are
      available. Actually, a possible middle ground between detailed and simplified
      models may be parsimonious models that represent the simplest approach that fits
      the application. The appropriate modelling approach depends on the research goal
      as well as on data available for correct model application. When there is
      inadequate data, it is mandatory to focus on a simple river water quality model
      rather than detailed ones. The study presents a parsimonious river water quality
      model to evaluate the propagation of pollutants in natural rivers. The model is
      made up of two sub-models: a quantity one and a quality one. The model employs a
      river schematisation that considers different stretches according to the
      geometric characteristics and to the gradient of the river bed. Each stretch is
      represented with a conceptual model of a series of linear channels and
      reservoirs. The channels determine the delay in the pollution wave and the
      reservoirs cause its dispersion. To assess the river water quality, the model
      employs four state variables: DO, BOD, NH(4), and NO. The model was applied to
      the Savena River (Italy), which is the focus of a European-financed project in
      which quantity and quality data were gathered. A sensitivity analysis of the
      model output to the model input or parameters was done based on the Generalised
      Likelihood Uncertainty Estimation methodology. The results demonstrate the
      suitability of such a model as a tool for river water quality management.

PMID- 20150697
TI  - Advances in membrane materials: desalination membranes based on directly
      copolymerized disulfonated poly(arylene ether sulfone) random copolymers.
AB  - The water and salt transport properties of chlorine tolerant disulfonated
      poly(arylene ether sulfone) (BPS) copolymers have been characterized. Cast BPS
      membranes of both salt form and acid form with sulfonation levels from 20% to 40%
      were investigated. Water permeability of BPS films increases more than one order
      of magnitude as sulfonation level increases from 20% to 40%, while the salt
      permeability of the corresponding membranes increases two orders of magnitude.
      Moderate salt rejection (98.2%) was achieved by a BPS salt form membrane with a
      sulfonation level of 20%.

PMID- 20150698
TI  - Sustainable domestic effluent reuse via Subsurface Drip Irrigation (SDI): alfalfa
      as a perennial model crop.
AB  - Scarcity of fresh high-quality water has heightened the importance of wastewater
      reuse primarily in dry regions together with improving its efficient use by
      implementing the Subsurface Drip Irrigation (SDI) method. Sustainable effluent
      reuse combines soil and plant aspects, along with the maintainability of the
      application system. In this study, field experiments were conducted for two years
      on the commercial farm of Revivim and Mashabay-Sade farm (RMF) southeast of the
      City of Beer-Sheva, Israel. The purpose was to examine the response of alfalfa
      (Medicago sativa) as a perennial model crop to secondary domestic effluent
      application by means of a SDI system as compared with conventional overhead
      sprinkler irrigation. Emitters were installed at different depths and spacing.
      Similar amounts of effluent were applied to all plots during the experimental
      period. The results indicated that in all SDI treatments, the alfalfa yields were
      11% to 25% higher than the ones obtained under sprinkler irrigated plots, besides
      the one in which the drip laterals were 200 cm apart. The average Water Use
      Efficiency (WUE) was better in all SDI treatments in comparison with the
      sprinkler irrigated plots. An economic assessment reveals the dependence of the
      net profit on the emitters' installation geometry, combined with the return for
      alfalfa in the market.

PMID- 20150699
TI  - Wastewater treatment and algal production in high rate algal ponds with carbon
      dioxide addition.
AB  - High rate algal ponds (HRAPs) provide improved wastewater treatment over
      conventional wastewater stabilisation ponds; however, algal production and
      recovery of wastewater nutrients as algal biomass is limited by the low
      carbon:nitrogen ratio of wastewater. This paper investigates the influence of
      CO(2) addition (to augment daytime carbon availability) on wastewater treatment
      performance and algal production of two pilot-scale HRAPs operated with different
      hydraulic retention times (4 and 8 days) over a New Zealand Summer (November
      March, 07/08). Weekly measurements were made of influent and effluent flow rate
      and water qualities, algal and bacterial biomass production, and the percentage
      of algae biomass harvested in gravity settling units. This research shows that
      the wastewater treatment HRAPs with CO(2) addition achieved a mean algal
      productivity of 16.7 g/m(2)/d for the HRAP(4d) (4 d HRT, maximum algae
      productivity of 24.7 g/m(2)/d measured in January 08) and 9.0 g/m(2)/d for the
      HRAP(8d) (8 d HRT)). Algae biomass produced in the HRAPs was efficiently
      harvested by simple gravity settling units (mean harvested algal productivity:
      11.5 g/m(2)/d for the HRAP(4d) and 7.5 g/m(2)/d for the HRAP(8d) respectively).
      Higher bacterial composition and the larger size of algal/bacterial flocs of the
      HRAP(8d) biomass increased harvestability (83%) compared to that of HRAP(4d)
      biomass (69%).

PMID- 20150700
TI  - Effects of ion exchange resins in different mobile ion forms on semi-aerobic
      landfill leachate treatment.
AB  - Landfill leachate is one of the major contamination sources. In this study, the
      ability of synthetic ion exchange resins which carry different mobile ion for
      removing color, chemical oxygen demand (COD), and ammonia nitrogen (NH(3)-N) from
      stabilized leachate was investigated. The synthetic resin INDION 225 Na as a
      cationic exchanger and INDION FFIP MB as an anionic exchanger were used in this
      study. INDION 225 Na was used in hydrogen form (H(+)) and in sodium form (Na(+)),
      while INDION FFIP MB resin was used in hydroxide form (OH(-)) and in calcium form
      (Cl(-)) form. The results indicated better removal of color, COD and NH(3)-N by
      using INDION 225 Na in H(+) as compared with Na(+) form, while no performance
      differences were observed by using INDION FFIP MB in OH(-) or Cl(-) form.
      Applying cationic resin followed by anionic resin achieved 97, 88 and 94, percent
      removal of color, COD and NH(3)-N. The residual amounts were 160 Pt-Co, 290 mg/L
      and 110 mg/L of color, COD and NH(3)-N respectively.

PMID- 20150701
TI  - Simultaneous online measurement of sulfide and nitrate in sewers for nitrate
      dosage optimisation.
AB  - A new method for the simultaneous online measurement of sulfide and nitrate in
      wastewater is developed. A UV-VIS spectrometer was used. The sensor was
      calibrated by means of simultaneous online and offline measurements of sulfide
      and nitrate in batch tests carried out on a laboratory-scale sewer system. The
      developed calibration algorithm was successfully validated for both sulfide and
      nitrate measurement, with confidence limits of 2.7 mg S/L for total dissolved
      sulfide, and 7.5 mg N/L for nitrate. The online measurement of sulfide and
      nitrate enabled detailed evaluation of seven nitrate dosing strategies in the
      laboratory-scale sewer system, providing strong support to process optimisation.
      The dosage optimisation revealed that nitrate should be added at a location close
      to the point of sulfide control rather than at the beginning of a rising main, at
      a rate proportional to the expected hydraulic retention time (HRT) of the
      wastewater in the sewer section between the point of nitrate addition and the
      point where sulfide control is desired.

PMID- 20150703
TI  - A membrane bioreactor for an innovative biological nitrogen removal process.
AB  - A hybrid system has been developed for biological nitrogen removal through
      nitrification-denitrification. The system includes an aerobic tank and an anoxic
      tank with an intermediate sludge settler connected to a membrane bioreactor (MBR)
      with a submerged 0.4 microm hollow-fiber membrane module. The laboratory system
      has a total working volume of 6.5 L treating a glucose-based synthetic
      wastewater. The experimental results demonstrate that the new process is highly
      effective for simultaneous organic and nitrogen removal. During the stationary
      operation, a sludge SS (suspended solids) concentration of 6 g/L or higher can be
      maintained in the reactors. The system has a COD (chemical oxygen demand) loading
      rate of up to 2,100 mg/L-d and a total nitrogen loading rate of up to 170 mg N/L
      d. More than 95% COD can be degraded, and the total nitrogen removal efficiency
      can be 90% or higher as the nitrogen is reduced from 100 to around 7.5 mg/L. A
      high quality effluent is produced with a SS of less than 1 mg/L. With the MBR,
      organic degradation, nitrogen removal and sludge-liquid separation can be well
      achieved within a short HRT of about 10 hr.

PMID- 20150702
TI  - Filterability of membrane bioreactor (MBR) sludge: impacts of polyelectrolytes
      and mixing with conventional activated sludge.
AB  - The main objective of this work was to investigate the filterability of MBR
      sludge and its mixture with conventional activated sludge (CAS). In addition, the
      impacts of type and dose of various polyelectrolytes, filter type and sludge
      properties on the filterability of both MBR and Mixed sludges were determined.
      Specific cake resistance (SCR) measured by the Buchner funnel filtration test
      apparatus and the solids content of the resulting sludge cake were used to assess
      the dewaterability of tested sludges. The type of filter paper used in Buchner
      tests affected the results of filterability for MBR, CAS and Mixed sludges. SCR
      values and optimum polyelectrolyte doses increased with increasing MLSS
      concentrations in the MBR, which suggested that increase in MLSS concentrations
      accompanied by increases in EPS and SMP concentrations and a shift toward smaller
      particles caused poorer dewaterability of the MBR sludge. The significant
      differences observed among the filterability of CAS and MBR sludges suggested
      that MLSS alone is not a good predictor of sludge dewaterability. Combining CAS
      and MBR sludges at different proportions generally improved their dewaterability.
      Combining MBR sludges having typically high MLSS and EPS concentrations with CAS
      having much lower MLSS concentrations may be an option for full-scale treatment
      plants experiencing sludge dewaterability problems. Better filterability and
      higher cake dry solids were achieved with cationic polyelectrolytes compared to
      anionic and non-ionic ones for all sludge types tested.

PMID- 20150704
TI  - Fate and levels of steroid oestrogens and androgens in waste stabilisation ponds:
      quantification by liquid chromatography-tandem mass spectrometry.
AB  - The capacity for removing wastewater-borne endocrine disrupting chemicals (EDCs)
      was investigated for two wastewater treatment plants (WWTPs) incorporating waste
      stabilisation ponds (WSPs) as the principal treatment technology. Samples were
      analysed for a number of steroidal oestrogens and androgens using liquid
      chromatography-tandem mass spectrometry (LC/MS/MS). Removal efficiency for
      steroid androgens was high for both WWTPs (93-100%) but WSP treatment was
      observed to be less effective for removing steroid oestrogens, particularly
      oestriol.

PMID- 20150705
TI  - Removal of magnetic resonance imaging contrast agents through advanced water
      treatment plants.
AB  - Stable gadolinium (Gd) complexes have been used as paramagnetic contrast agents
      for magnetic resonance imaging (MRI) for over 20 years, and have recently been
      identified as environmental contaminants. As the rare earth elements (REE), which
      include Gd, are able to be measured accurately at very low concentrations (e.g.
      Tb is measured at 7 fmol/kg in this study) using inductively coupled plasma mass
      spectrometry (ICP-MS), it is possible to determine the fate of this class of
      compounds during the production of purified recycled water from effluent.
      Coagulation and microfiltration have negligible removal, with the major removal
      step occurring across the reverse osmosis membrane where anthropogenic Gd (the
      amount of Gd attributable to MRI contrast agents) is reduced from 0.39 nmol/kg to
      0.59 pmol/kg, a reduction of 99.85%. The RO concentrate has anthropogenic Gd
      concentrations of 2.6 nmol/kg, an increase in concentration in line with the
      design characteristics of the plant. The increased concentration in the RO
      concentrate may allow further development of anthropogenic Gd as a tracer of the
      fate of the RO concentrate in the environment.

PMID- 20150706
TI  - Potentiometric polymeric membrane electrodes for mercury detection using
      calixarene ionophores.
AB  - It is here established that potentiometric polymeric membrane electrodes based on
      electrically neutral ionophores are a useful analytical tool for the detection of
      heavy metal ions from environmental and industrial waste water. PVC based
      membrane containing p-tert-butyl-calix[4]arenethioether derivative as active
      material along with sodiumtetraphenylborate (NaTPB) as solvent mediator and
      dibutylphthalate as a plasticizer in the ratio 45:9:460:310 (w/w%)
      (I:NaTPB:DBP:PVC) exhibits good properties with a Nernstian response of 29.50+/
      1.0 mV per decade of activity and a working concentration range of 7.2 x 10(-8)
      1.0 x 10(-1) M. The electrode gave more stable potential readings when used
      around pH 2.5-6.8 and exhibits fast response time of 14 s. The sensors were found
      to work satisfactorily in partially non-aqueous media up to 40% (v/v) content of
      acetone, methanol or ethanol and could be used over a period of 7-9 months.
      Excellent selectivity for Hg(2+) ions is indicated by match potential method and
      fixed interference method. The sensors could be used successfully in the
      estimation of mercury in different sample.

PMID- 20150707
TI  - Fate of nitrogen species in nitrate reduction by nanoscale zero valent iron and
      characterization of the reaction kinetics.
AB  - This study investigates the fate of nitrogen species during nitrate reduction by
      nanoscale zero valent iron (NZVI) as well as the related kinetics. The NZVI used
      for the experiments was prepared by chemical reduction without a stabilizing
      agent. The pseudo first order kinetic constant of nitrate reduction at 30 degrees
      C with an NZVI/nitrate ratio of 1.25:1, which were the reference conditions of
      this study, was 4.08 h(-1) (R(2)=0.955). A nitrogen mass balance was established
      by quantitative analysis of aqueous-phase and gas-phase nitrogen species. The
      results confirm that the nitrate was converted to ammonium ion, that ammonia
      stripping subsequently occurred under a strong alkaline condition, and that the
      total amount of aqueous nitrogen was consequently reduced. The nitrate reduction
      rate also increased with a lower pH and a higher temperature when microscale ZVI
      was used. However, in contrast to the reaction by microscale ZVI, the nitrate
      reduction rate by NZVI was higher for an unbuffered condition, possibly due to
      the abundance of surface atoms and the smaller size.

PMID- 20150709
TI  - High yield hydrogen production in a single-chamber membrane-less microbial
      electrolysis cell.
AB  - The single-chamber membrane-less MEC exerted much better hydrogen production
      performance while given higher applied voltages than it did at lower. High
      applied voltages that could shorten the reaction time and the exposure of anode
      to air for at least 30 min between cycles can significantly suppress methanogen
      and increase hydrogen production. At an applied voltage of 1.0 V, a hydrogen
      production rate of 1.02 m(3)/m(3)/day with a current density of 5.7 A/m(2) was
      achieved. Cathodic hydrogen recovery and coulombic efficiency were 63.4% and
      69.3% respectively. The hydrogen concentration of mixture gas produced of 98.4%
      was obtained at 1.0 V, which was the best result of reports. The reasons that
      such a high hydrogen concentration can be achieved were probably the high
      electrochemical activity and hydrogen production capability of the active
      microorganisms. Increase in substrate concentrations could not improve MEC's
      performance, but increased the reaction times. Further, reactor configuration and
      operation factors optimisation should be considered to increase current density,
      hydrogen production rate and hydrogen recovery.

PMID- 20150708
TI  - Modelling waste stabilisation ponds with an extended version of ASM3.
AB  - In this paper an extended version of IWA's Activated Sludge Model No 3 (ASM3) was
      developed to simulate processes in waste stabilisation ponds (WSP). The model
      modifications included the integration of algae biomass and gas transfer
      processes for oxygen, carbon dioxide and ammonia depending on wind velocity and a
      simple ionic equilibrium. The model was applied to a pilot-scale WSP system
      operated in the city of Florianopolis (Brazil). The system was used to treat
      leachate from a municipal waste landfill. Mean influent concentrations to the
      facultative pond of 1,456 g(COD)/m(3) and 505 g(NH4-N)/m(3) were measured.
      Experimental results indicated an ammonia nitrogen removal of 89.5% with
      negligible rates of nitrification but intensive ammonia stripping to the
      atmosphere. Measured data was used in the simulations to consider the impact of
      wind velocity on oxygen input of 11.1 to 14.4 g(O2)/(m(2) d) and sun radiation on
      photosynthesis. Good results for pH and ammonia removal were achieved with mean
      stripping rates of 18.2 and 4.5 g(N)/(m(2) d) for the facultative and maturation
      pond respectively. Based on measured chlorophyll a concentrations and depending
      on light intensity and TSS concentration it was possible to model algae
      concentrations.

PMID- 20150710
TI  - Recovery of nickel ions from simulated electroplating rinse water by
      electrodeionization process.
AB  - Pure water production and recovery of Ni(2+) from dilute NiSO(4) solution via
      improved electrodeionization (EDI) process were investigated. It was indicated
      that, with the feed water containing 50 mg L(-1) Ni(2+), the dilute resistivity
      of the EDI could achieve 3 MOmega cm which gave a Ni(2+) rejection more than
      99.8% while the Ni(2+) was concentrated as high as 1,583 mg L(-1) in the
      concentrate stream. The current efficiency was as high as 40% and the concentrate
      factor could reach 31.7. The experiment results demonstrated that, just in a
      single process, it was feasible to purifying and concentrating dilute nickel
      wastewater synchronously by the EDI technology.

PMID- 20150711
TI  - Investigation of aerobic and anaerobic ammonium-oxidising bacteria presence in a
      small full-scale wastewater treatment system comprised by UASB reactor and three
      polishing ponds.
AB  - This work applied PCR amplification method and Fluorescence in situ hybridisation
      (FISH) with primers and probes specific for the anammox organisms and aerobic
      ammonia-oxidising beta-Proteobacteria in order to detect these groups in
      different samples from a wastewater treatment system comprised by UASB reactor
      and three polishing (maturation) ponds in series. Seven primer pairs were used in
      order to detect Anammox bacteria. Positive results were obtained with three of
      them, suggesting that Anammox could be present in polishing pond sediments.
      However, Anammox bacteria were not detected by FISH, indicating that they were
      not present in sediment samples, or they could be present but below FISH
      detection limit. Aerobic ammonia- and nitrite-oxidising bacteria were verified in
      water column samples through Most Probable Number (MPN) analysis, but they were
      not detected in sediment samples by FISH. Ammonia removal efficiencies occurred
      systematically along the ponds (24, 32, and 34% for polishing pond 1, 2, and 3,
      respectively) but the major reaction responsible for this removal is still
      unclear. Some nitrification might have occurred in water samples because some
      nitrifying bacteria were present. Also Anammox reaction might have occurred
      because Anammox genes were detected in the sediments, but probably this reaction
      was too low to be noticed. It is important also to consider that some of the
      ammonia removal observed might be related to NH(3) stripping, associated with the
      pH increase resulting from the intensive photosynthetic activity in the ponds
      (mechanism under investigation). Therefore, it can be concluded that more than
      one mechanism (or reaction) might be involved in the ammonia removal in the
      polishing ponds investigated in this study.

PMID- 20150712
TI  - A comparison of the legal frameworks supporting water management in Europe and
      China.
AB  - This paper has compared the legal frameworks supporting water management in
      Europe and China, with special focus on integrated river basin management (IRBM)
      to identify synergies and opportunities in policymaking and implementation. The
      research shows that China has committed to the efficient management of water
      resources through various policy tools during the current period. This
      commitment, however, has often been interrupted and distorted by politics,
      resulting in the neglect of socioeconomic and environmental priorities. The
      European legal framework supporting water management underwent a complex and
      lengthy development, but with the adoption of the Water Framework Directive
      provides a policy model on which to develop an integrated and sustainable
      approach to river basin management, elements of which may help to meet the
      demands of the emerging 21st century Chinese society on these critical natural
      resources.

PMID- 20150713
TI  - Inhibitory effects of golden thread (Coptis chinensis) and berberine on
      Microcystis aeruginosa.
AB  - The effects of 40 Chinese herbs on Microcystis aeruginosa growth were monitored
      spectrophotometrically. Golden thread (Coptis chinensis) exhibited the best
      inhibitory effects. Cell density of M. aeruginosa decreased with the increasing
      concentrations of golden thread and the prolongation of exposure time. Decreases
      in protein content, carbohydrate content, and chlorophyll a content were observed
      in a golden thread concentration-dependent manner after 96 h exposure. Changes in
      cell density, protein content, carbohydrate content, and chlorophyll a content of
      M. aeruginosa exposed to berberine, the main component of golden thread, were
      also investigated. It was observed that berberine exhibited the same inhibitory
      effects on M. aeruginosa. The results suggested that golden thread could inhibit
      M. aeruginosas growth effectively, and berberine might be the main allelochemical
      implementing the inhibitory effects of golden thread.

PMID- 20150714
TI  - Effect of anoxic decay process on simultaneous nitrification denitrification in a
      membrane bioreactor operated without an anoxic tank.
AB  - This study was focused on evaluating the role and the effect of anoxic decay on
      the extent of simultaneous nitrification-denitrification (SNdN) process sustained
      in a single membrane bioreactor. The membrane bioreactor was fed with relatively
      strong domestic sewage and operated at steady state at a sludge age of 36 days at
      a corresponding suspended solids level maintained in the range of 17,500-21,000
      mg/L. The SNdN could be sustained due to diffusion limitation of oxygen into the
      flocs. The evaluation identified an MLSS threshold level of around 17,000-18,000
      mg/L below which nitrogen removal was essentially controlled by denitrification
      and above, the rate limiting mechanism shifted to nitrification maintaining total
      nitrogen removal efficiency of 85-95% for a typical domestic sewage. The
      contribution of anoxic decay process to the overall denitrification potential was
      evaluated as 60%, substantially higher than the remaining 40% associated with the
      anoxic growth during the SNdN process.

PMID- 20150715
TI  - Nitrification potential in waste stabilisation ponds: comparison of a secondary
      and tertiary pond system.
AB  - This study compared the nitrification potential of two separate Waste
      Stabilisation Ponds (WSPs) operating under differing physical and chemical
      conditions. In order to probe the nitrification potential of each system, the
      oxidation of ammonium and also the intermediate product nitrite was assessed
      using both in situ and laboratory micro-scale incubations. The role of sediment
      in determining the nitrification potential of the two WSPs was also investigated.
      Results from laboratory microcosm incubations revealed a competent and strikingly
      similar nitrification potential for both WSPs in spite of their differing
      nitrogen and organic loadings, and also suggested a significant role for sediment
      in WSP nitrogen cycling. Results from in situ field experiments identified
      biomass uptake to be the dominant nitrogen removal mechanism in natural pond
      environments. Other aspects of WSP nitrogen cycling are also discussed.

PMID- 20150716
TI  - Treatment of the azo dye direct blue 2 in a biological aerated filter under
      anaerobic/aerobic conditions.
AB  - The main objective of this research was to determine the feasibility to treat the
      azo dye direct blue 2 together with municipal wastewater in a biological aerated
      filter (BAF) using lava stones as support of the microorganisms and under
      combined anaerobic/aerobic conditions. A 3 m high pilot biological aerated filter
      was fed with municipal wastewater and, after several weeks, the azo dye direct
      blue 2 was added to the wastewater to reach a final concentration of 50 mg/L (34
      mgCOD/L). Under continuous operation, two strategies were tested: Alternating
      aeration (12 h anaerobic and 12 h aerobic) and combined aeration (the lower part
      of the filter anaerobic and the upper part aerobic). The results indicate that
      municipal wastewater acted as a good electron donor resulting in satisfactory COD
      and dye removal rates. Better dye removal (61%) was obtained with combined
      aeration than with alternating aeration (45%). After beginning the azo dye
      addition, the COD removal rates decreased from 87 to 81% for both alternating and
      combined aeration procedures. The average ammonia nitrogen removal, without the
      addition of the dye, was 73% and increased to 90% shortly after beginning the dye
      addition, then it decreased to 81% during the combined aeration period. Excellent
      nitrification was observed in the upper aerobic part of the filter. For the
      combined aeration phase, the conditions change from anaerobic to aerobic does not
      seem to affect the behavior of the COD and TSS curves.

PMID- 20150717
TI  - Nitrification in brackish water recirculating aquaculture system integrated with
      activated packed bed bioreactor.
AB  - Recirculation aquaculture systems (RAS) depend on nitrifying biofilters for the
      maintenance of water quality, increased biosecurity and environmental
      sustainability. To satisfy these requirements a packed bed bioreactor (PBBR)
      activated with indigenous nitrifying bacterial consortia has been developed and
      commercialized for operation under different salinities for instant nitrification
      in shrimp and prawn hatchery systems. In the present study the nitrification
      efficiency of the bioreactor was tested in a laboratory level recirculating
      aquaculture system for the rearing of Penaeus monodon for a period of two months
      under higher feeding rates and no water exchange. Rapid setting up of
      nitrification was observed during the operation, as the volumetric total ammonia
      nitrogen removal rates (VTR) increased with total ammonia nitrogen (TAN)
      production in the system. The average Volumetric TAN Removal Rates (VTR) at the
      feeding rate of 160 g/day from 54-60th days of culture was 0.1533+/-0.0045 kg
      TAN/m(3)/day. The regression between VTR and TAN explained 86% variability in VTR
      (P<0.001). The laboratory level RAS demonstrated here showed high performance
      both in terms of shrimp biomass yield and nitrification and environmental quality
      maintenance. Fluorescent in-situ Hybridization analysis of the reactor biofilm
      ensured the presence of autotrophic nitrifier groups such as Nitrosococcus
      mobilis lineage, Nitrobacter spp and phylum Nitrospira, the constituent members
      present in the original consortia used for activating the reactors. This showed
      the stability of the consortia on long term operation.

PMID- 20150718
TI  - Efficient degradation of MtBE and other gasoline-originated compounds by means of
      a biological reactor of novel conception: two case studies in Italy and the USA.
AB  - The presence of MtBE in groundwaters, due to its past use as an oxygenate
      additive to "green" gasoline, poses potential threats to human health as a
      possible carcinogen. As its chemical properties render it very mobile and poorly
      treatable by means of bioremediation, chemical oxidation, stripping, or carbon
      adsorption, a new, ex-situ treatment process was recently developed by the US EPA
      and the University of Cincinnati. The objective of the study was to evaluate the
      effectiveness of this pump-and-treat technology in actual contaminated
      groundwater plumes in the field in two different conditions. The technology based
      on the combination of aerobic degradation and a special filtration medium is
      simple to operate, easily meets the challenge of producing a highly polished
      effluent in a cost-effective fashion, compared to other processes.

PMID- 20150719
TI  - Characterisation of pathogenic bacteria in a UASB-polishing pond system using
      molecular techniques.
AB  - Molecular techniques have been commonly used to detect and quantify pathogenic
      bacteria in food, clinical and environmental samples, but in wastewater treatment
      plants few studies have been carried out. This work applied PCR with a specific
      set of primers to investigate pathogenic bacteria in a wastewater plant comprised
      of a UASB reactor followed by polishing ponds. In addition, in-situ hybridisation
      technique (FISH) was used to estimate the abundance of Escherichia coli in the
      system. According to the PCR results it was observed that Escherichia coli and
      Salmonella enterica subsp. enterica were not completely removed in the system,
      since they were detected either in the raw sewage or UASB and pond effluents.
      Shigella dysenteriae and Enterococcus spp. were detected in raw sewage and UASB,
      but not in the pond effluent. In contrast Staphylococcus aureus and Helicobacter
      pylori were not detected in any samples. The quantification of E. coli using FISH
      revealed values in the range of 10(7) cells/100 mL for raw sewage and 10(6)
      cells/100 mL for pond effluent, slightly higher than values obtained by
      traditional techniques. Finally the results show the applicability of PCR method
      for monitoring pathogenic bacteria in wastewater systems; however, more samples
      need to be analysed in order to certify the applicability of FISH to estimate
      pathogenic bacteria in WWT effluents.

PMID- 20150720
TI  - Hypokalemic periodic paralysis associated with thyrotoxicosis, renal tubular
      acidosis and nephrogenic diabetes insipidus.
AB  - A 19-year-old girl presented at our emergency room with hypokalemic periodic
      paralysis. She had a thyrotoxic goiter and had experienced three paralytic
      attacks during the previous 2 years on occasions when she stopped taking
      antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had
      metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced
      ability to acidify urine during spontaneous metabolic acidosis was confirmed by
      detection of coexisting distal renal tubular acidosis (RTA). The polyuria and
      polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed
      using the water deprivation test and vasopressin administration. Her recurrent
      and frequent paralytic attacks may have been the combined effects of
      thyrotoxicosis and RTA. Although the paralytic attack did not recur after
      improving the thyroid function, mild acidosis and nephrogenic DI have been
      remained subsequently. Patients with TPP, especially females with atypical
      metabolic features, should be investigated for possible precipitating factors.

PMID- 20150721
TI  - Relation of Gamma-glutamyltransferase and alcohol drinking with incident
      diabetes: the HIPOP-OHP study.
AB  - AIM: Gamma-glutamyltransferase (GGT) is known to correlate well with alcohol
      consumption; however, the relation between GGT and diabetes and that between
      alcohol consumption and diabetes mellitus (DM) is inconsistent. Thus, several
      questions, such as whether light to moderate drinkers can be considered as low
      risk for diabetes incidence irrespective of their GGT level, is unresolved. In
      this study, we investigated the relation of GGT or alcohol drinking with DM
      incidence considering the body mass index (BMI) in healthy Japanese workers.
      METHODS: We followed 3095 men who did not have DM at baseline for 4 years.
      Incident diabetes was defined as a fasting (non-fasting) plasma glucose level of
      >or=7.0 (11.1) mmol/L, or treatment of diabetes. Multiple adjusted hazard ratios
      (HR) were calculated using Cox proportional models. RESULTS: Participants with
      higher GGT (GGT >or=27 IU/L) showed an increased risk of diabetes incidence even
      when their BMI level was low. Although a U-shaped relation between alcohol
      drinking and incident diabetes was observed, the risk to light to moderate
      drinkers (alcohol <23 g/day) was not low if they were either overweight (BMI
      >or=25 kg/m(2)) or had higher GGT (HR=2.60, p=0.08) or both overweight and higher
      GGT (HR=3.16, p=0.07) compared with never drinkers without higher GGT and
      overweight. CONCLUSIONS: Higher GGT was associated with a higher incidence of DM
      irrespective of drinking status or obesity. Although a U-shaped relation between
      alcohol drinking and incident diabetes was observed, the risk to light to
      moderate drinkers was not low if they were either overweight or had higher GGT.

PMID- 20150722
TI  - Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with
      hypercholesterolemia.
AB  - AIM: Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to
      reduce the intestinal absorption of cholesterol. We investigated whether it also
      has beneficial effects on metabolic disorder and/or renal insufficiency in
      patients with hypercholesterolemia. METHODS: Ezetimibe was administered to 38
      Japanese patients with hypercholesterolemia to obtain appropriate low-density
      lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with
      hypercholesterolemia (n=38) were the controls. We evaluated the effects of
      ezetimibe before and 4 to 8 weeks after ezetimibe treatment. RESULTS: Ezetimibe
      significantly decreased LDL-chol levels and metabolic syndrome-related factors,
      including body weight, waist circumference, blood pressure; homeostasis model
      assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were
      significantly reduced. In addition, it decreased the level of high-sensitivity C
      reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary
      excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and
      increased the urinary excretion of nitrate and nitrite (NOx). In the controls we
      observed no such changes. Excepting the decrease in the serum TNF-alpha level,
      the effects of ezetimibe were not correlated with decreased LDL-chol levels.
      CONCLUSION: Ezetimibe ameliorated the status of metabolic syndrome and
      microalbuminuria, reduced inflammation and oxidative stress, and increased nitric
      oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.

PMID- 20150723
TI  - Cell type differentiation dynamics in the developing porcine retina.
AB  - The dynamics of retinal embryogenesis have been well characterized previously in
      terms of cell proliferation, genesis and migration, whereas overall cell type
      differentiation within the retinal layers has been less thoroughly explored. In
      the present study, phenotypical differentiation of all 7 major retinal cell types
      was examined in the developing porcine retina using one cell-specific
      immunohistochemical marker per cell type. At the end of the first trimester at
      E39 (39 days after gestation), neurofilament labeled ganglion cells, recoverin
      labeled photoreceptors, vimentin labeled Muller cells and synaptophysin labeled
      presynaptic vesicles were found. Rhodopsin labeled rod photoreceptors were
      present at E60, whereas cone transducin labeled cone photoreceptors were not seen
      until E99. Differentiation of inner nuclear cells coincided with the appearance
      of the retinal layers at E70-E99 with the presence of parvalbumin labeled
      amacrine cells, calbindin labeled horizontal cells and PKC labeled rod bipolar
      cells. At postnatal day 4, all retinal subtypes except for cone photoreceptors
      displayed a labeling pattern corresponding to the one found in the adult porcine
      retina. The immunohistochemical labeling pattern suggests that phenotypic
      differentiation of the 7 principal retinal cell types in the porcine retina
      follows a central-to-peripheral spatio-temporal gradient similar to the one
      reported for cell proliferation and genesis. Differentiation of the non-laminated
      retinal cell mass appears to be initiated at its outer and inner margins and
      progresses inwards, a process which ends in the formation of the characteristic
      plexiform and nuclear layers. The dynamics of retinal cell type differentiation
      are of interest from a biological standpoint and are also important for
      therapeutical strategies in retinal degenerative disease.

PMID- 20150724
TI  - Preferences for hereditary breast and ovarian cancer information among Mexican,
      Cuban and Puerto Rican women at risk.
AB  - BACKGROUND: Little is known about the preferences of at-risk Hispanic women to
      gain information on hereditary breast and ovarian cancer (HBOC). AIMS: This study
      sought to qualitatively explore preferences for HBOC information among at-risk
      Mexican, Puerto Rican and Cuban women and to pilot a mock brochure aimed at
      Hispanic women. METHODS: Hispanic women aged 18-65 years with a personal or
      family history of breast or ovarian cancer participated in a semistructured
      interview. Data were analyzed using a combination of open-coding and content
      analysis. RESULTS: Fifty-three women participated in the study. For the majority
      of content areas, there were no major differences between the subethnicities. All
      women reported discussing cancer with a doctor after a family member had been
      diagnosed and discussing cancer within their families; however, the content of
      the discussion varied. Cuban and Puerto Rican women reported using the Internet
      routinely for health care information while Mexican women said they did not have
      access to computers and did not use them. All women liked the content and photos
      in the brochure but Mexican women thought the reading level was too high.
      Preferences for the spokesperson focused on the need for Spanish-speaking health
      care providers. CONCLUSIONS: While the data show some similarities, such as
      patterns of cancer discussion and appreciation of the mock brochure, there were
      differences between the groups on information preferences. In designing HBOC
      education information for Hispanic audiences, it is important to consider varied
      channels for dissemination and preferences for specific types of information
      across subethnicities.

PMID- 20150725
TI  - Comparative effect of green tea, chokeberry and honeysuckle polyphenols on
      nutrients and mineral absorption and digestibility in rats.
AB  - BACKGROUND/AIMS: Natural polyphenols are chemically and biologically active. This
      study aimed at examining the physiological effects of high doses of polyphenol
      extracts from green tea and new polyphenol-rich sources (chokeberry and
      honeysuckle fruits) on nutrient absorption. METHODS: 32 male Wistar rats were
      divided into four groups and fed a diet supplemented with one of the three
      polyphenolic extracts (at 0.4%) or a control diet for 4 weeks. A perfusion
      technique was used to study the effects at intestinal level. Pure polyphenols
      from the three sources were introduced into perfusion fluid at a concentration of
      0.4% and allowed to cross the intestinal tract in 1.5 h. RESULTS: In the
      perfusion experiment, addition of the extracts caused a strong and statistically
      significant reduction in absorption of the selected nutrients (water, glucose,
      cholesterol, amino acids and minerals) compared to control animals. In the
      nutritional experiment, we recorded a slight decrease in diet utilization and
      growth in rats on polyphenolic diets relative to control group. In the same
      experiment, we observed a reduction of Zn and Cu absorption, but this was not
      accompanied by diminished concentrations in the bone femur. CONCLUSIONS: The
      presence of the polyphenolic extracts in the perfusion liquids significantly
      reduced absorption from the small intestine, but the nutritional experiment did
      not confirm deleterious consequences of the consumption of high extract doses.

PMID- 20150726
TI  - Successful treatment of severe hypertriglyceridemia with a formula diet rich in
      omega-3 fatty acids and medium-chain triglycerides.
AB  - BACKGROUND: Patients with highly increased plasma triglyceride levels are at risk
      of developing serious complications such as pancreatitis, coronary heart disease
      and stroke. Therefore it is important to rapidly decrease plasma triglyceride
      levels. A sufficient control of triglyceride levels with drugs like fibrates,
      statins or nicotinic acid can usually only be attained after a couple of weeks.
      Plasma exchange appears to be a fast but expensive method to reduce triglyceride
      levels. In this study we describe the use of a new omega-3 fatty acid and medium
      chain triglyceride-rich formula diet as a therapeutic concept to reduce plasma
      triglyceride levels fast and effectively. METHODS: Thirty-two patients with
      severe hypertriglyceridemia were treated with the especially composed formula
      diet for a period of 7 days. RESULTS: Within this period of time, plasma
      triglycerides decreased from 1,601 (402-4,555) to 554 (142-2,382) mg/dl (p <
      0.05). Total cholesterol levels were reduced from 417 (211-841) to 287 (165-457)
      mg/dl (p < 0.001). Fasting glucose and uric acid levels also slightly decreased (
      8%; -12%). The formula diet as a 1-week treatment was well tolerated and accepted
      by the patients. CONCLUSION: This diet was successfully used as an acute
      treatment in severe hypertriglyceridemia and showed effectiveness in rapidly and
      safely lowering plasma triglyceride levels.

PMID- 20150727
TI  - Round window membrane implantation with an active middle ear implant: a study of
      the effects on the performance of round window exposure and transducer tip
      diameter in human cadaveric temporal bones.
AB  - OBJECTIVES: To assess the importance of 2 variables, transducer tip diameter and
      resection of the round window (RW) niche, affecting the optimization of the
      mechanical stimulation of the RW membrane with an active middle ear implant
      (AMEI). MATERIALS AND METHODS: Ten temporal bones were prepared with combined
      atticotomy and facial recess approach to expose the RW. An AMEI stimulated the RW
      with 2 ball tip diameters (0.5 and 1.0 mm) before and after the resection of the
      bony rim of the RW niche. The RW drive performance, assessed by stapes velocities
      using laser Doppler velocimetry, was analyzed in 3 frequency ranges: low (0.25-1
      kHz), medium (1-3 kHz) and high (3-8 kHz). RESULTS: Driving the RW produced mean
      peak stapes velocities (H(EV)) of 0.305 and 0.255 mm/s/V at 3.03 kHz,
      respectively, for the 1- and 0.5-mm tips, with the RW niche intact. Niche
      drilling increased the H(EV) to 0.73 and 0.832 mm/s/V for the 1- and 0.5-mm tips,
      respectively. The tip diameter produced no difference in output at low and medium
      frequencies; however, the 0.5-mm tip was 5 and 6 dB better than the 1-mm tip at
      high frequencies before and after niche drilling, respectively. Drilling the
      niche significantly improved the output by 4 dB at high frequencies for the 1-mm
      tip, and by 6 and 10 dB in the medium- and high-frequency ranges for the 0.5-mm
      tip. CONCLUSION: The AMEI was able to successfully drive the RW membrane in
      cadaveric temporal bones using a classical facial recess approach. Stimulation of
      the RW membrane with an AMEI without drilling the niche is sufficient for
      successful hearing outputs. However, the resection of the bony rim of the RW
      niche significantly improved the RW stimulation at medium and higher frequencies.
      Drilling the niche enhances the exposure of the RW membrane and facilitates
      positioning the implant tip.

PMID- 20150728
TI  - Effects of age and working memory capacity on pitch pattern sequence test and
      dichotic listening.
AB  - This study assessed the effects of age and working memory capacity on dichotic
      listening and temporal sequencing. Double Dichotic Digit Test (DDT), Pitch
      Pattern Sequence Test (PPST) and Digit Span Test were administered on 40 healthy
      adults with hearing thresholds of not greater than 30 dB HL across octave
      frequencies from 250 to 4000 Hz. Twenty young (20-30 years old) and 20 older (50
      65 years old) adults were included in the study. Results showed that the older
      group had significantly lower scores in DDT, PPST and working memory capacity
      measures than the young subjects. Working memory capacity was positively
      correlated with PPST but not with DDT, suggesting that DDT might be more auditory
      modality-specific than PPST.

PMID- 20150730
TI  - Quality of life of patients with Alzheimer's disease: differential perceptions
      between spouse and adult child caregivers.
AB  - BACKGROUND/AIMS: Little research has been conducted into differences in the
      perceived quality of life of patients (QoL-p) when comparing spouse and adult
      child caregivers of people with Alzheimer's disease (AD). The aim of this study
      was to identify the differential variables in perceived QoL-p between patients
      and carers, distinguishing between spouse and adult child caregivers. METHOD:
      Cross-sectional analytic study of 251 patients and their carers (spouses: 112;
      adult children: 139) using the QoL-AD scale and sociodemographic and clinical
      data. RESULTS: The more positive perception of spouses was associated with higher
      educational levels of the caregiver and greater functional autonomy in the
      patient. The more negative perception of adult children was associated with
      greater caregiver burden and higher levels of depression in the patient. The
      perception of daughter caregivers showed the strongest association with mental
      health and burden. CONCLUSIONS: Spouse caregivers have a more positive perception
      of the patient's quality of life than adult child caregivers.

PMID- 20150729
TI  - Anosognosia for behavioral disturbances in frontotemporal dementia and
      corticobasal syndrome: A voxel-based morphometry study.
AB  - BACKGROUND: Patients with syndromes of the frontotemporal dementia spectrum are
      frequently unaware of their behavioral changes. METHODS: Seventy patients with a
      clinical diagnosis of behavioral variant frontotemporal dementia (bv-FTD, n =
      27), aphasic variant frontotemporal dementia (a-FTD, n = 12) and corticobasal
      syndrome (CBS, n = 31) participated in the study. Anosognosia for behavioral
      disturbances was measured as discrepancy between caregiver's and patient's
      ratings on the Frontal Systems Behavior Scale for present and premorbid
      behavioral symptoms. Voxel-based morphometry analysis of MRI data was performed
      to explore the association between anosognosia and gray matter loss. RESULTS:
      Although behavioral symptoms were reported in all the groups, the comparison
      between present and premorbid anosognosia revealed that bv-FTD patients not only
      underestimated their present behavioral disturbances compared to their
      caregivers, but also overestimated their premorbid behavioral disturbances.
      Across all groups, the degree of anosognosia for present behavioral impairment
      correlated with gray matter atrophy in a posterior region of the right superior
      temporal sulcus (adjacent to the temporoparietal junction). CONCLUSION: These
      results confirm the role of the right temporoparietal cortex in the genesis of
      anosognosia and suggest that, in clinical syndromes of the frontotemporal
      dementia spectrum, anosognosia is associated with the dysfunction of
      temporoparietal mechanisms of self versus others knowledge.

PMID- 20150731
TI  - Effects of a physical training programme on cognitive function and walking
      efficiency in elderly persons with dementia.
AB  - OBJECTIVES: To study the effects of physical stimulation based on walking
      exercises, equilibrium and endurance on cognitive function and walking efficiency
      in patients with dementia. METHODS: Randomized controlled trial including 31
      subjects suffering from dementia (age: 81.8 +/- 5.3 years). The intervention
      group (n = 16) benefited from a 15-week physical activity programme involving
      three 1-hour sessions per week. The control group (n = 15) did not practice any
      physical activities. Before and after rehabilitation, all subjects were evaluated
      with the Rapid Evaluation of Cognitive Functions test (ERFC French version) and
      walking analysis. RESULTS: After the 15 weeks of rehabilitation, the subjects
      from the intervention group improved their overall ERFC score (p < 0.01), while
      those in the control group decreased their overall ERFC score. Interactions were
      also observed between walking parameters and groups (p < 0.01); the intervention
      group improved walking capacities through heightened walking speed, stride length
      and a reduction in double limb support time. Lastly, the subjects from the
      control group presented a reduction in both walking speed and stride length.
      CONCLUSION: This study shows that a physical activity programme can slow
      cognitive decline and improve quality of walking in elderly persons suffering
      from dementia.

PMID- 20150732
TI  - Predicting gains in dementia caregiving.
AB  - BACKGROUND: Caregiver gain is an important yet less-explored phenomenon. Being
      conceptually distinct from burden, factors associated with burden and gain can
      differ. This study aims to explore factors associated with the experience of
      gains in dementia caregiving. METHOD: Cross-sectional study involving caregivers
      recruited from a tertiary hospital dementia clinic and the local Alzheimer's
      Association. Caregivers completed a questionnaire containing the following
      scales: gain in Alzheimer's care Instrument (GAIN), General Health Questionnaire
      (GHQ-28), Dementia Management Strategies Scale (DMSS), Revised Memory and
      Behavioral Problems Checklist (RMBPC) and Zarit Burden Interview (ZBI).
      Demographic information for the person with dementia (PWD) and the caregiver was
      also recorded. Initial screening with univariate analyses (t tests, ANOVAs,
      Pearson's correlations) was performed to identify significant (p < 0.05)
      variables, which were then entered into a multiple regression model to identify
      variables associated with gain. RESULT: The final sample comprised 334 caregivers
      with a mean age of 51.5 years (SD = 10.9, range = 22-85), the majority of whom
      where Chinese (94.6%) females (71%). Mean GAIN score was 30 (SD = 6.6, range = 7
      40). Regression analysis identified 3 factors significantly associated with gains
      (adjusted R(2) 32.3%): mental well-being of the caregiver, use of active
      management as a caregiving strategy, and participation in caregiver educational
      and support group programmes. CONCLUSION: The results have important implications
      for caregiver interventions. Interventions should target maintaining mental well
      being, encouraging participation in educational and support programmes, and
      teaching appropriate coping and dementia specific management strategies to derive
      good outcomes.

PMID- 20150733
TI  - Time trend in diagnosing dementia in secondary care.
AB  - BACKGROUND: To study the trend of diagnosing dementia in the secondary health
      care sector over time, we conducted a nationwide longitudinal study of the
      incidence and prevalence of registered dementia diagnoses in the Danish national
      hospital registers. METHODS: All Danish residents born before 1964 and alive at
      their 40th birthday were followed from their 40th birthday or January 1, 1970,
      whichever came later, to the date of the first dementia diagnosis recorded in the
      hospital registers, the date of emigration, date of death, or December 31, 2004,
      whichever came first. The age- and period-specific incidence and prevalence of
      dementia were calculated and compared to estimates from large community-based
      cohort studies in Europe. RESULTS: The study population consisted of 4,723,838
      persons with 81,090,583 person-years of follow-up. 154,152 dementia cases were
      registered from 1970 to 2004. The incidence and prevalence of registered dementia
      diagnoses showed an increasing trend over time. In 2003, the age-standardized
      incidence rate ratio was 0.66 when compared to estimates from large European
      community-based cohort studies. CONCLUSIONS: The study shows a marked improvement
      in the diagnostic rate of dementia in secondary care over time and indicates that
      this sector can be an important point of entry for patients with dementia.

PMID- 20150734
TI  - The Wechsler Digit Symbol Substitution Test as the best indicator of the risk of
      impaired driving in Alzheimer disease and normal aging.
AB  - AIMS: Our purpose was to identify cognitive tools associated with unsafe driving
      among elderly drivers of varying cognitive levels. METHODS: Twenty drivers with
      early-stage dementia of the Alzheimer type and 56 nondemented drivers aged 65-85
      were recruited. Various cognitive processes were measured and unsafe driving was
      evaluated during an in-traffic road test with 3 different indicators and a
      composite indicator. RESULTS: The Wechsler Digit Symbol Substitution Test score
      was the best cognitive measure to detect unsafe drivers using the composite
      driving indicator. CONCLUSION: The Digit Symbol Substitution Test may be used by
      physicians for the evaluation and follow-up of older patients, with or without
      Alzheimer-type dementia, as a screening tool of unsafe driving.

PMID- 20150735
TI  - Incidence of mild cognitive impairment: a systematic review.
AB  - BACKGROUND/AIMS: Subjects with mild cognitive impairment (MCI) constitute a risk
      population of developing dementia and thus a population of clinical interest.
      This study reviews recent work on the incidence of MCI in the elderly. METHODS:
      Incidence papers were identified by a systematic literature search. Studies on
      the incidence of MCI were considered if they identified 'cognitively mildly
      impaired' subjects by application of the MCI criteria, used the 'person-years-at
      risk' method, and were based on population- or community-based samples. RESULTS:
      Nine studies were identified. The incidence of amnestic MCI subtypes ranged
      between 9.9 and 40.6 per 1,000 person-years, and the incidence of non-amnestic
      MCI subtypes was 28 and 36.3 per 1,000 person-years. Regarding any MCI, incidence
      rates of 51 and 76.8 per 1,000 person-years were found. A higher risk of incident
      MCI mainly resulted for higher age, lower education and hypertension. DISCUSSION:
      The incidence rates of MCI varied widely, and possible risk factors for incident
      MCI were analysed only to a limited extent. The findings call for an agreement
      concerning the criteria used for MCI and the operationalisation of these
      criteria.

PMID- 20150737
TI  - Multifocal motor neuropathy: update on clinical characteristics,
      pathophysiological concepts and therapeutic options.
AB  - Multifocal motor neuropathy (MMN) is an acquired immune-mediated neuropathy
      characterized by chronic or stepwise progressive asymmetrical limb weakness
      without sensory deficits. The upper extremities are more often affected than the
      lower extremities with distal paresis dominating over proximal paresis. Important
      diagnostic features are persistent multifocal partial conduction blocks (CBs) and
      the presence of high-titer anti-GM1 serum antibodies. Motor neuron disease, other
      chronic dysimmune neuropathies, such as chronic inflammatory demyelinating
      polyneuropathy and the Lewis-Sumner syndrome (MADSAM neuropathy), are important
      differential diagnoses. While corticosteroids and plasma exchange are largely
      ineffective, high-dose intravenous immunoglobulins are regarded as first-line
      treatment. In spite of significant success in elucidating the underlying disease
      mechanisms in MMN during the past few years, important pathophysiological issues
      and the optimum long-term therapy remain to be clarified. The present review
      summarizes the clinical picture and current pathophysiological concepts of MMN
      with a special focus on the molecular and electrophysiological basis of CBs and
      highlights established therapies as well as possible novel treatment options.

PMID- 20150736
TI  - Increased number of CpG island hypermethylation in tumor suppressor genes of non
      neoplastic gastric mucosa correlates with higher risk of gastric cancer.
AB  - BACKGROUND/AIM: We investigated the relationship of gastric cancer (GC) and CpG
      island hypermethylation (CIHM) in tumor suppressor genes of non-neoplastic
      gastric mucosa. METHODS: Gastric mucosa samples were obtained from 125 GC and 180
      non-GC subjects. CIHM of p14, p16, DAP-kinase and CDH1 genes were determined by
      methylation-specific polymerase chain reaction. High CIHM was defined as three or
      all methylated CpG islands. RESULTS: Rates of CIHM of p14, CDH1, DAP-kinase, and
      high CIHM were significantly higher in all GC samples than non-GC samples (p14:
      32.2 vs. 50.4%; OR = 1.70, 95% CI = 1.03-2.80, p = 0.04, CDH1: 36.1 vs. 84.0%; OR
      = 8.65, 95% CI = 14.74-15.77, p < 0.0001, DAP-kinase: 42.2 vs. 83.2%; OR = 5.98,
      95% CI = 3.37-10.62, p < 0.0001, and high CIHM: 44.4 vs. 80.8%; OR = 4.40, 95% CI
      = 2.51-7.72, p < 0.0001). CIHM in CDH1 and DAP-kinase were associated with a
      greater risk of GC including all of its different subtypes. An increased number
      of CIHM was associated with an increased risk of all GC (1 CIHM; OR = 2.33, 95%
      CI = 0.82-6.64, p = 0.11, 2 CIHM; OR = 4.89, 95% CI = 1.79-13.37, p = 0.002, 3
      CIHM; OR = 9.43, 95% CI = 3.20-27.78, p < 0.0001, and all CIHM OR = 24.71, 95% CI
      = 6.70-91.18, p < 0.0001). Three and all CIHM were closely associated with a
      higher risk of intestinal-type GC, Helicobacter pylori-positive infection status,
      male gender, and middle and older GC while 3 CIHM was closely associated with a
      higher risk of diffuse-type GC, H. pylori-negative infection status and younger
      GC. CONCLUSIONS: CIHM of CDH1 and DAP-kinase in non-neoplastic gastric mucosa
      corresponded to a risk of GC regardless of histological subtype, H. pylori
      infection status, gender and generation. An increased number of CIHM correlates
      with a higher GC risk including its various clinico-pathological subtypes.

PMID- 20150738
TI  - Transcranial magnetic stimulation for drug-resistant epilepsies: rationale and
      clinical experience.
AB  - Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation
      technique which, over the last 25 years, has greatly expanded from a simple
      method for stimulating the motor cortex to an invaluable tool with multiple
      research, diagnostic and even therapeutic applications. In this review, we
      discuss the use of repetitive TMS as a means of suppressing cortical
      hyperexcitability in drug-resistant epilepsies. The theoretical background and
      the experimental evidence in favor of this novel therapeutic approach are
      presented, and a number of open-label and controlled studies in patients with
      various forms of focal epilepsy are reviewed. It is concluded that, although the
      therapeutic effects of repetitive TMS in epilepsy appear rather limited, further
      clinical testing of this rapidly evolving technology is warranted.

PMID- 20150739
TI  - Transitory blocking of pulmonary artery and veins as a novel strategy in
      pulmonary surgery: an experimental study in a rabbit model.
AB  - BACKGROUNDS: Transitory blocking of the pulmonary artery and veins is now being
      applied in the treatment of local advanced non-small cell lung cancer in our
      department. We performed this study to establish a pulmonary vessel blocking
      model in rabbits and investigate the features of lung ischemia-reperfusion
      injury. METHODS: 126 New Zealand rabbits were randomized into 3 groups: group I,
      sham group; group II, left pulmonary artery blocking, and group III, left
      pulmonary artery and veins blocking. The physiological data as well as the blood
      and tissue samples were harvested at the time of thoracotomy, at 1 h after
      ischemia and 1, 2, 4, 6 and 24 h after reperfusion, respectively. Lung injury was
      assessed histologically by determining the levels of malondialdehyde, superoxide
      dismutase, myeloperoxidase and water content. RESULTS: The hemodynamics were
      stable in all three groups. The levels of malondialdehyde, myeloperoxidase, and
      water content of lung tissue were all significantly increased in groups II and
      III when compared with group I at 1, 2, 4 and 6 h after reperfusion. They almost
      all returned to baseline at 24 h after reperfusion. However, there was no
      significant difference observed between groups II and III at either time point. A
      similar change in the process of lung ischemia-reperfusion injury was observed
      under light and electron microscopes in group II and in group III. CONCLUSIONS:
      The features of lung ischemia-reperfusion injury were similar when blocking the
      pulmonary artery and veins compared with blocking the pulmonary artery alone.
      Moreover, it might be safe to block the pulmonary vessels within 1 h during
      pulmonary surgery.

PMID- 20150740
TI  - Smoking attenuates increase in exhaled nitric oxide in atopic but not in
      nonatopic young adults with asthma.
AB  - BACKGROUND: Measurement of fractional exhaled nitric oxide (FENO) is useful in
      assessing eosinophilic airway inflammation. Smoking may modify airway
      inflammation and reduce FENO levels, compromising the diagnostic value of FENO in
      smokers. How smoking influences FENO in atopic versus nonatopic asthmatics is
      unknown. The aim of the present study was to compare FENO in atopic and nonatopic
      steroid-naive young asthmatic adults and in healthy subjects in terms of smoking.
      METHODS: Forty-six (30 atopic) smoking and 70 (54 atopic) nonsmoking steroid
      naive army conscripts (mean age 20 years) with current symptomatic asthma
      underwent FENO measurement, skin prick tests, spirometry with a bronchodilation
      test, bronchial histamine challenge, and a standardized exercise test. Ten
      healthy smokers and 9 healthy nonsmokers underwent FENO measurement, spirometry
      and bronchial histamine challenge. RESULTS: Smokers with asthma showed
      significantly higher FENO than did healthy smokers and nonsmokers (p = 0.001,
      both comparisons). Among atopic asthmatics, FENO was lower in smokers than in
      nonsmokers (p = 0.002) whereas among nonatopic asthmatics no such difference was
      detectable (p = 0.89). However, even among nonatopic asthmatic smokers FENO was
      significantly higher than among healthy controls (p = 0.01). CONCLUSION: Smoking
      seems to attenuate the increase in FENO in atopic but not in nonatopic
      asthmatics. This finding suggests differences in biochemical mechanisms of NO
      formation in atopic and nonatopic asthma. However, FENO was significantly higher
      both in atopic and nonatopic asthmatic smokers than in healthy controls. This
      suggests that FENO can be applied for diagnostic purposes also in young adult
      smokers.

PMID- 20150741
TI  - Sensitization to inhaled ryegrass pollen by collateral priming in a murine model
      of allergic respiratory disease.
AB  - BACKGROUND: Mouse models of asthma suffer from the necessity to prime the animals
      by injections before respiratory exposure. Our aim was to develop a mouse model
      that mimics the progression of human allergic disease upon low-dose inhaled
      allergen exposure. METHODS: Mice were primed intraperitoneally to ovalbumin (OVA)
      before they were exposed repeatedly to aerosols of either OVA, ryegrass (Lolium
      perenne) pollen extract, or both concomitantly. The sensitization to ryegrass
      pollen proteins was evaluated by measurement of specific serum antibody, by the
      respiratory response to a challenge with ryegrass pollen extract and by lung
      cytokine production after challenge. RESULTS: Inhalation of ryegrass pollen
      extract alone did not result in sensitization. Sensitization to inhaled ryegrass
      pollen proteins, however, did occur in mice that had been sensitized to OVA by
      intraperitoneal injections and were then exposed to inhaled ryegrass pollen
      extract and OVA simultaneously. T and B cell priming was ascertained by ryegrass
      pollen-specific IgG1 and IgE antibody production and by induction of airway
      inflammation and of Th2 cytokine mRNA transcripts in the lungs upon airway
      challenge with ryegrass pollen extract. A progressive spread of the IgE/IgG1
      response to different ryegrass pollen proteins could be visualized in immunoblots
      by comparing antibody patterns at day 56 and 86. CONCLUSIONS: Low-dose inhalatory
      allergen exposure results in sensitization when airways are exposed at the same
      time to another allergen to which the animals are already sensitized. This model
      can help to unravel the mechanisms that underlie the development and progression
      of respiratory allergic diseases.

PMID- 20150742
TI  - The T cell response to major grass allergens is regulated and includes IL-10
      production in atopic but not in non-atopic subjects.
AB  - BACKGROUND: The incidence of allergic diseases is increasing in industrialized
      countries and the immunological mechanisms leading to tolerance or allergy are
      poorly understood. Cytokines with suppressive abilities and CD4(+)CD25(+)
      regulatory T cells have been suggested to play a central role in allergen
      specific responses. The aim was to determine whether major grass allergens induce
      production of suppressive cytokines in allergic and healthy subjects and to
      examine the inhibitory effect of these cytokines on allergic responses. METHODS:
      Peripheral blood mononuclear cells (PBMCs) were isolated from healthy and grass
      allergic donors and stimulated with the major grass allergens Phl p 1 or Phl p 5.
      The effects of endogenous IL-10 and/or TGF-beta on proliferation and cytokine
      production were determined by use of blocking antibodies. In addition, the number
      of CD4(+)CD25(+) T cells and their expression of chemokine receptors were
      investigated by flow cytometry. RESULTS: Phl p 1 and Phl p 5 induced IL-10
      production, which down-regulated proliferation and cytokine production, in PBMC
      cultures from atopic but not from non-atopic donors. Comparable frequencies of
      CD4(+)CD25(+) T cells were present in PBMCs in the two groups, but fewer cells
      from atopic donors were CD4(+)CD25(+)CCR4(+) and more cells were
      CD4(+)CD25(+)CLA(+) compared to healthy donors. CONCLUSION: Allergen-specific
      responses of grass allergic patients but not in non-atopic subjects are
      influenced by regulatory cytokines produced in response to the important
      allergens. Differences in CD4(+)CD25(+) T cell expression of chemokine receptors
      in allergic compared to non-atopic donors could suggest that the homing of
      CD4(+)CD25(+) T cells is important for the regulation of allergen-specific
      responses.

PMID- 20150743
TI  - The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project.
AB  - The role of genetic and environmental factors, as well as their interaction, in
      the natural history of asthma, allergic rhinitis and chronic obstructive
      pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of
      large-scale analytical epidemiological/genetic studies aimed at investigating
      these 3 respiratory conditions simultaneously. The GEIRD project is a
      collaborative initiative designed to collect information on biomarkers of
      inflammation and oxidative stress, individual and ecological exposures, diet,
      early-life factors, smoking habits, genetic traits and medication use in large
      and accurately defined series of asthma, allergic rhinitis and COPD phenotypes.
      It is a population-based multicase-control design, where cases and controls are
      identified through a 2-stage screening process (postal questionnaire and clinical
      examination) in pre-existing cohorts or new samples of subjects. It is aimed at
      elucidating the role that modifiable and genetic factors play in the occurrence,
      persistence, severity and control of inflammatory airway diseases, by way of the
      establishment of a historical multicentre standardized databank of phenotypes,
      contributed by and openly available to international epidemiologists. Researchers
      conducting population-based surveys with standardized methods may contribute to
      the public-domain case-control database, and use the resulting increased power to
      answer their own scientific questions.

PMID- 20150744
TI  - Presenting features of feather duvet lung.
AB  - BACKGROUND: Feather duvet lung (FDL) is a rare subgroup of bird fancier's lung.
      It is caused by inhalation of organic dust due to goose or duck feathers in
      duvets or pillows. METHODS: A retrospective review of the medical records of 13
      patients with FDL was performed to assess the specific history and review
      clinical characteristics of patients with this disease. RESULTS: All patients
      were female with a mean age of 53 years (26-71). They were recently exposed to
      feather duvets (6), pillows (1) or both (6). Specific histories were duvets or
      pillows filled with raw goose feathers from their own farms (4), intensive
      contact with goose feathers in youth (3), and bird exposure prior to symptom
      onset (5). In all patients specific IgG antibodies to goose and/or duck feathers
      were detected. Pulmonary function tests revealed a moderate to severe reduced
      diffusion capacity and a mild restrictive pattern. High-resolution computed
      tomography was performed in 11 patients and demonstrated predominantly ground
      glass opacities (10) and fibrosis (6). In bronchoalveolar lavage fluid,
      lymphocytic alveolitis was demonstrated in all patients. Lung biopsies were
      obtained in 9 patients and demonstrated lymphocytic alveolitis (8), granulomas
      (3), bronchiolitis obliterans organizing pneumonia pattern (2), and usual
      interstitial pneumonia pattern (1). CONCLUSIONS: The clinical findings of FDL are
      typical of extrinsic allergic alveolitis. Primary sensitization could be due to
      former exposure to bird antigens at home or goose/duck feather exposure in youth.
      In view of the increasing popularity of feather duvets, FDL should be considered
      in the differential diagnosis of patients with extrinsic allergic alveolitis.

PMID- 20150745
TI  - Work-related allergy and asthma in spice mill workers - The impact of processing
      dried spices on IgE reactivity patterns.
AB  - BACKGROUND: Three spice mill workers developed work-related allergy and asthma
      after prolonged exposure to high levels (>10 mg/m(3)) of inhalable spice dust.
      Patterns of sensitization to a variety of spices and putative allergens were
      identified. METHODS: Work-related allergy and asthma were assessed on history,
      clinical evaluation, pulmonary function and fractional exhaled nitric oxide.
      Specific IgE reactivity to a range of common inhalant, food and spice allergens
      was evaluated using ImmunoCAP and allergen microarray. The presence of non-IgE
      mediated reactions was determined by basophil stimulation (CAST-ELISA). Specific
      allergens were identified by immunoblotting to extracts of raw and dried
      processed garlic, onion and chili pepper. RESULTS: Asthma was confirmed in all 3
      subjects, with work-related patterns prominent in worker 1 and 3. Sensitization
      to multiple spices and pollen was observed in both atopic workers 1 and 2,
      whereas garlic and chili pepper sensitization featured in all 3 workers.
      Microarray analysis demonstrated prominent profilin reactivity in atopic worker
      2. Immunoblotting demonstrated a 50-kDa cross-reactive allergen in garlic and
      onion, and allergens of approximately 40 and 52 kDa in chili pepper. Dry powdered
      garlic and onion demonstrated greater IgE binding. CONCLUSIONS: This study
      demonstrated IgE reactivity to multiple spice allergens in workers exposed to
      high levels of inhalable spice dust. Processed garlic and onion powder
      demonstrated stronger IgE reactivity than the raw plant. Atopy and
      polysensitization to various plant profilins, suggesting pollen-food syndrome,
      represent additional risk factors for sensitizer-induced work-related asthma in
      spice mill workers.

PMID- 20150746
TI  - Indoor determinants of endotoxin and dust mite exposures in Hong Kong homes with
      asthmatic children.
AB  - BACKGROUND: Domestic endotoxin enhances airway inflammation and increases asthma
      severity in Caucasian children, but little data are published on indoor endotoxin
      exposure in Asian countries. This study investigated house dust endotoxin and Der
      p 1 levels in Hong Kong families with asthmatic children, and their effects on
      asthma severity. METHODS: 115 asthmatics from a pediatric clinic underwent
      fractional exhaled nitric oxide (FeNO) and spirometric measurements. Home visits
      were then made within 2 weeks, during which parents completed the International
      Study of Asthma and Allergies in Childhood questionnaire. Settled dust was
      collected from patients' mattresses, bedroom floors and living room floors.
      Endotoxin and Der p 1 were measured by limulus amebocyte lysate and immunoassay,
      respectively. RESULTS: Endotoxin was detectable in all locations from all
      families, whereas Der p 1 was detectable in 58-70% of indoor sites. Floors of
      both bedroom and living rooms had higher endotoxin but lower Der p 1 levels than
      mattresses (p < 0.001 for both). Mattress endotoxin level correlated inversely
      with Der p 1 level (r = -0.308, p = 0.001). Household smoker, feather bedding and
      vacuum cleaning were independent determinants of indoor endotoxin. Timing of last
      bedding change was associated with Der p 1 levels at all sites. Mattress
      endotoxin level was associated with frequency of wheezing episodes (p = 0.044),
      but neither endotoxin nor Der p 1 was associated with FeNO and spirometric
      parameters. CONCLUSIONS: Domestic endotoxin levels are associated with frequency
      of wheezing episodes in asthmatic children but not their FeNO or spirometric
      measurements.

PMID- 20150747
TI  - The effect of generalist and specialist care on quality of life in asthma
      patients with and without allergic rhinitis.
AB  - BACKGROUND: Treatment of asthma and rhinitis patients is often provided by both
      generalists (GPs) and specialists (SPs). Studies have shown differences in
      clinical outcomes of treatment between these settings. The aim of this study was
      to evaluate the effect of GP and SP care on health-related quality of life
      (HRQoL). MATERIALS AND METHODS: Three hundred and eight asthma and allergic
      rhinitis patients randomized to 3 years' treatment by an SP or GP were examined
      at baseline and at study completion. At both examinations, the HRQoL was measured
      with the Standardized Asthma Quality of Life Questionnaire (AQLQ) and the
      Rhinitis Quality of Life Questionnaire (RQLQ). RESULTS: In the SP care, a
      significant improvement from baseline was found in HRQoL for both AQLQ total
      scores (6.19 +/- 0.1 vs. 6.44 +/- 0.1, respectively; p < 0.001) and RQLQ total
      scores (0.80 +/- 0.1 vs. 0.58 +/- 0.1, respectively; p <0.01). Patients in the GP
      care setting experienced no change in HRQoL total scores during the study.
      However, improvements were found predominantly in patients with concomitant
      rhinitis. Although no change in AQLQ was found in the GP setting in this group
      with double disease, an association between change in RQLQ and AQLQ was found (r
      = -0.245, p < 0.05, and r = -0.324, p < 0.001, respectively). CONCLUSION: The
      results provide evidence that compared with GP care, SP care leads to an
      improvement in both asthma and rhinitis quality of life. This is especially
      pronounced in patients with concomitant asthma and rhinitis and supports the
      guidelines recommending that SPs should monitor patients with complicated
      disease.

PMID- 20150748
TI  - The cannabinoid receptor agonist WIN 55,212-2 inhibits antigen-induced plasma
      extravasation in guinea pig airways.
AB  - BACKGROUND: Although neurogenic inflammation of the airways via activation of C
      fibers is thought to be important in the pathogenesis of asthma, the mechanisms
      regulating C-fiber activity remain uncertain. OBJECTIVE: The influence of a
      cannabinoid receptor agonist, WIN 55,212-2, on C-fiber activation in guinea pig
      airways was investigated, as was the mechanism by which cannabinoids regulate
      antigen-induced airway inflammation. METHODS: The inhibitory effect of WIN 55,212
      2 on antigen-induced plasma extravasation was assessed in guinea pig tracheal
      tissues by photometric measurement of extravasated Evans blue dye after
      extraction with formamide. RESULTS: Pretreatment with WIN 55,212-2 (0.001, 0.01
      or 0.1 mg/kg) significantly and dose-dependently reduced tracheal plasma
      extravasation induced by inhaling a 5% ovalbumin solution for 2 min after
      pretreatment with a neutral endopeptidedase inhibitor (phosphoramidon at 2.5
      mg/kg i.v.). A cannabinoid CB2 receptor antagonist (SR144528) blunted the
      inhibitory effect of WIN 55,212-2, while a cannabinoid CB1 antagonist (SR141716A)
      did not. Pretreatment with a neurokinin-1 receptor antagonist (FK888)
      significantly reduced ovalbumin-induced extravasation of Evans blue dye.
      Pretreatment with the combination of WIN 55,212-2 and FK888 reduced antigen
      induced plasma extravasation more markedly than FK888 alone. CONCLUSIONS: These
      findings suggest that WIN 55,212-2 inhibits C-fiber activation via the
      cannabinoid CB2 receptor and thus suppresses antigen-induced inflammation in
      guinea pig airways.

PMID- 20150749
TI  - Corticosteroids for the treatment and prevention of bronchopulmonary dysplasia.

PMID- 20150751
TI  - Incidence of retinopathy of prematurity over the last decade in the Central
      Netherlands.
AB  - BACKGROUND AND OBJECTIVES: To retrospectively analyze changes in incidence and
      risk factors of retinopathy of prematurity (ROP) over two periods, 10 years
      apart, in the central Netherlands. METHODS: Data of 570 infants admitted between
      2001 and 2005, screened for ROP according to the Dutch National guideline, were
      compared to those of 538 infants admitted between 1991 and 1995. RESULTS:
      Incidence of ROP decreased significantly over the last decade (40.9% in 1991-1995
      vs. 23.3% in 2001-2005, p < 0.001), together with incidence of severe ROP (stage
      >or=3) (3.3 vs. 1.2%, p < 0.05). In infants with a birth weight (BW) <1,000 g
      incidence of ROP dropped significantly (67.0 vs. 41.8%, p < 0.001), as well as
      incidence of severe ROP (8.1 vs. 3.0%, p < 0.05). For infants with a BW >or=1,000
      g incidence of ROP also declined significantly (27.1 vs. 13.0%, p < 0.001), that
      of severe ROP remained unchanged (0.8 vs. 0.3%). In both periods gestational age,
      duration of artificial ventilation, small for gestational age (SGA) and postnatal
      steroids were independent risk factors for ROP. CONCLUSIONS: In the central
      Netherlands, incidence of ROP and severe ROP has significantly decreased, also in
      infants with BW <1,000 g. Risk factors remained unchanged.

PMID- 20150750
TI  - Postnatal hydrocortisone for preventing or treating bronchopulmonary dysplasia in
      preterm infants: a systematic review.
AB  - BACKGROUND: Corticosteroids have been used widely after birth in preterm infants
      with respiratory failure; hydrocortisone may be preferable to other
      corticosteroids for this purpose. OBJECTIVES: To determine if postnatal
      hydrocortisone is useful to prevent or treat bronchopulmonary dysplasia (BPD) in
      preterm infants. METHODS: Randomised controlled trials (RCTs) of postnatal
      hydrocortisone therapy to prevent or treat BPD were sought. Data regarding
      clinical outcomes including mortality, BPD, death or BPD, complications during
      the primary hospitalisation, and long-term outcome were abstracted and analysed
      using RevMan 5. RESULTS: Eight RCTs enrolling a total of 880 participants were
      eligible. In all trials treatment was started in the first week of life; there
      were no trials of treatment started in infants who were chronically ventilator
      dependent after the first week of life with established or evolving BPD. A meta
      analysis of the available trials demonstrated little evidence for a direct effect
      of hydrocortisone on the rates of BPD, mortality, or the combined outcome of BPD
      or mortality. Hydrocortisone in the doses used in these eight studies had few
      beneficial or harmful effects; the notable exception was an increase in
      gastrointestinal perforation. CONCLUSIONS: Postnatal hydrocortisone in the doses
      and regimens used in the reported trials has few beneficial or harmful effects
      and cannot be recommended for prevention of BPD. There are no randomised trials
      to substantiate the use of hydrocortisone in chronically ventilator-dependent
      infants with established or evolving BPD.

PMID- 20150752
TI  - Comparison of hearing improvement and complications after stapes surgery with and
      without potassium titanyl phosphate laser for manipulation of the foot plate.
AB  - OBJECTIVE: The purpose of the current study was to evaluate the differences in
      hearing results and complications between the conventional technique (CT) and
      potassium titanyl phosphate laser (KTP) laser-assisted stapes surgery that does
      not involve the manipulation of the foot plate. METHODS: Ninety-eight ears with
      conductive or mixed hearing loss due to otosclerosis were operated on by using
      the CT or KTP laser-assisted manipulation. The results of pure-tone audiometry,
      the duration of postoperative vestibular symptoms, and the presence of damage to
      the foot plate were reviewed retrospectively. RESULTS: The extent of hearing
      improvement and the duration of vestibular symptoms were not significantly
      different between the two groups. The damage to the foot plate was significantly
      less frequent in the KTP group compared to the CT group. Profound sensorineural
      hearing loss occurred in one case in the CT group, whereas no significant
      sensorineural hearing loss was detected in the KTP group. CONCLUSIONS: According
      to our present findings, KTP laser-assisted surgery was safer than CT in terms of
      the damage to the foot plate even when the KTP laser was not used for opening the
      foot plate. However, both techniques showed similar results in hearing
      improvement and vestibular symptoms.

PMID- 20150753
TI  - Effects of fentanyl pretreatment on regional cerebral blood flow in focal
      cerebral ischemia in rats.
AB  - BACKGROUND: There are reports that opioid preconditioning induces opioid-receptor
      dependent neuroprotection against cerebral ischemia. This experiment was
      performed to test whether pretreatment with fentanyl, a synthetic primary mu
      opioid receptor agonist, would affect the regional cerebral blood flow (rCBF) in
      focal cerebral ischemia in rats. METHODS: Twenty-four hours before permanent and
      unilateral middle cerebral artery (MCA) occlusion, rats were pretreated with
      normal saline, 200 microg/kg of fentanyl i.p. or 500 microg/kg of fentanyl i.p.
      The rats were anesthetized with isoflurane and were mechanically ventilated to
      cannulate the vessels and to occlude MCA. One hour after MCA occlusion, the rCBF
      was measured using (14)C-iodoantipyrine. RESULTS: The cortical rCBF decreased 1 h
      after MCA occlusion in all the experimental groups. In the ischemic cortex, the
      rCBF of the rats treated with 500 microg/kg of fentanyl was significantly greater
      (+80%, p < 0.05) than that of the control animals. The rCBF of the ischemic
      cortex of the rats treated with fentanyl 200 microg/kg seemed higher than in the
      control animals, but the difference was not statistically significant. The rCBF
      was similar in the nonischemic brain regions such as the contralateral cortex or
      pons among the experimental groups. CONCLUSION: Our data demonstrated that
      pretreatment with fentanyl improved the rCBF in the focal ischemic area without
      change in rCBF in the nonischemic cortex. Our data suggest that fentanyl could be
      effective in improving the rCBF in the focal ischemic area when used as a
      preconditioning agent and that improvement of rCBF could be one of the
      contributing factors of neuroprotection by opioid preconditioning.

PMID- 20150754
TI  - Nephroprotective effect of telmisartan in rats with ischemia/reperfusion renal
      injury.
AB  - We investigated the protective effect of telmisartan, an angiotensin II receptor
      antagonist, against ischemia/reperfusion renal injury in rats. Bilateral ischemia
      was induced by clamping both renal vascular pedicles for 45 min followed by
      reperfusion for 3 h. Untreated rats exposed to ischemia/reperfusion showed
      significant elevations in blood urea nitrogen and serum creatinine levels, renal
      tissue levels of malondialdehyde, tumor necrosis factor-alpha and nitric oxide,
      and caspase-3 activity. This was associated with significant decreases in renal
      reduced glutathione level, catalase and superoxide dismutase activities. Also,
      significant increases in serum and renal tissue levels of homocysteine were
      detected following ischemia/reperfusion. Pre-ischemic treatment with telmisartan
      (0.3 mg/kg/day, i.p.) for 7 consecutive days significantly attenuated the
      increases in blood urea nitrogen, serum creatinine, renal malondialdehyde, tumor
      necrosis factor-alpha, nitric oxide, caspase-3 activity, and serum and renal
      homocysteine levels, and significantly restored the renal antioxidant defenses.
      In addition, light and electron microscopic examinations revealed that
      telmisartan pre-treatment markedly ameliorated ischemia/reperfusion-induced renal
      tissue damage. It was concluded that telmisartan, through its antioxidant, anti
      inflammatory and antiapoptotic effects, can be considered a potential candidate
      to protect against acute ischemia/reperfusion renal injury.

PMID- 20150755
TI  - Biomarkers for breast cancer: the search continues.

PMID- 20150756
TI  - HSP110 improves the anti-tumor effects of the cytotoxic T lymphocyte epitope E749
      57 in mice: HSP110 as a peptide specific chaperone or adjuvant?

PMID- 20150757
TI  - Recent surprising similarities between plant cells and neurons.
AB  - Plant cells and neurons share several similarities, including non-centrosomal
      microtubules, motile post-Golgi organelles, separated both spatially/structurally
      and functionally from the Golgi apparatus and involved in vesicular endocytic
      recycling, as well as cell-cell adhesion domains based on the actin/myosin
      cytoskeleton which serve for cell-cell communication. Tip-growing plants cells
      such as root hairs and pollen tubes also resemble neurons extending their axons.
      Recently, surprising discoveries have been made with respect of the molecular
      basis of neurodegenerative disorders known as Hereditary Spastic Paraplegias and
      tip-growth of root hairs. All these advances are briefly discussed in the context
      of other similarities between plant cells and neurons.

PMID- 20150758
TI  - Neutralization of Clostridium difficile toxin A using antibody combinations.
AB  - The pathogenicity of Clostridium difficile (C. difficile) is mediated by the
      release of two toxins, A and B. Both toxins contain large clusters of repeats
      known as cell wall binding (CWB) domains responsible for binding epithelial cell
      surfaces. Several murine monoclonal antibodies were generated against the CWB
      domain of toxin A and screened for their ability to neutralize the toxin
      individually and in combination. Three antibodies capable of neutralizing toxin A
      all recognized multiple sites on toxin A, suggesting that the extent of surface
      coverage may contribute to neutralization. Combination of two noncompeting
      antibodies, denoted 3358 and 3359, enhanced toxin A neutralization over
      saturating levels of single antibodies. Antibody 3358 increased the level of
      detectable CWB domain on the surface of cells, while 3359 inhibited CWB domain
      cell surface association. These results suggest that antibody combinations that
      cover a broader epitope space on the CWB repeat domains of toxin A (and
      potentially toxin B) and utilize multiple mechanisms to reduce toxin
      internalization may provide enhanced protection against C. difficile-associated
      diarrhea.

PMID- 20150759
TI  - Sarcosine as a potential prostate cancer biomarker and therapeutic target.

PMID- 20150760
TI  - Combined therapy with the RANKL inhibitor RANK-Fc and rhApo2L/TRAIL/dulanermin
      reduces bone lesions and skeletal tumor burden in a model of breast cancer
      skeletal metastasis.
AB  - In bone metastases, tumor cells interact with the bone microenvironment to induce
      osteoclastogenesis, leading to bone destruction and the growth factor release. 
      RANK ligand (RANKL) is essential for osteoclast formation, function, and
      survival.  Tumor cell-mediated osteolysis is thought to occur ultimately via
      induction of RANKL within the bone stroma, and inhibition of RANKL in models of
      breast cancer bone metastases blocks tumor-induced osteolysis and reduces
      skeletal tumor burden.  In addition, the skeleton is co-opted by tumor cells and
      functions as a supportive tumor microenvironment.  Inhibition of RANKL, by
      reducing tumor-induced osteoclastogenesis, may reduce the local release of growth
      factors and calcium which may potentially enhance the anti-tumor activity of
      cytotoxic or direct tumor apoptotic agents.  Recombinant human Apo2 ligand/ TNF
      related apoptosis-inducing ligand (rhApo2L/TRAIL/dulanermin) is a dual pro
      apoptotic receptor agonist that preferentially induces apoptosis in cancer cells
      versus normal cells.  We therefore examined RANKL inhibition (using RANK-Fc) in
      combination with rhApo2L/TRAIL on tumor-induced osteolysis and skeletal tumor
      burden in a murine intracardiac injection model of MDA-MB-231 breast carcinoma
      bone metastasis.  rhApo2L/TRAIL treatment resulted in a rapid reduction of
      skeletal tumor burden. Treatment with RANK-Fc prevented osteolytic lesions and
      reduced skeletal tumor burden. Combining RANK-Fc with rhApo2L/TRAIL was superior
      to either rhApo2L/TRAIL or RANK-Fc alone at reducing skeletal tumor burden in the
      bone metastasis model.  Our findings show that RANKL inhibition effectively
      inhibits pathologic osteolysis induced by human breast adenocarcinoma MDA-MB-231
      cells in animals with established tumors, and also enhances the ability of
      rhApo2L/TRAIL to reduce skeletal tumor burden in vivo.

PMID- 20150761
TI  - Targeting the checkpoint kinase WEE1: selective sensitization of cancer cells to
      DNA-damaging drugs.

PMID- 20150762
TI  - Conatumumab, a fully human agonist antibody to death receptor 5, induces
      apoptosis via caspase activation in multiple tumor types.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to death
      receptors 4 and 5 (DR4, DR5) to transduce apoptotic signals. Conatumumab (AMG
      655) is an investigational, fully human monoclonal agonist antibody (IgG(1)) to
      human DR5, which induces apoptosis via caspase activation. In this study, we
      demonstrate that conatumumab binds to DR5, activating intracellular caspases in
      vitro in the presence of a cross-linker. We also show that conatumumab has
      activity in vivo and inhibits tumor growth in colon (Colo205 and HCT-15), lung
      (H2122) and pancreatic (MiaPaCa2/T2) xenograft models. Conatumumab also enhances
      the antitumor activity of chemotherapeutics in vivo. Caspase activation in
      Colo205 tumors is dose-dependent and correlated with serum concentrations of
      conatumumab. We demonstrate for the first time that increases in serum caspase
      3/7 activity and levels of M30 (neoepitope of caspase-cleaved cytokeratin-18) are
      linked to activation of the extrinsic apoptotic pathway using conatumumab in a
      preclinical model. These data suggest that conatumumab has potential as a
      therapeutic agent for treating patients with multiple tumor types, and that serum
      caspase-3/7 and M30 levels may serve as biomarkers of conatumumab activity.

PMID- 20150763
TI  - Dynein- and activity-dependent retrograde transport of autophagosomes in neuronal
      axons.
AB  - The accumulation of autophagosomes within axons is often observed in axonopathies
      associated with various neurological disorders, including those following
      excitotoxic insults. Nevertheless, the life cycle of autophagosomes in axons is
      not well understood. In the present study, we used microexplant cultures of
      cerebellar granule cells from GFP-LC3 transgenic mice to perform time-lapse
      imaging of LC3-positive dots in identified axons. Since these GFP-LC3 dots were
      never observed in granule cells on an Atg5-null background, they were considered
      to represent autophagosomes. Under physiological conditions, the autophagosomes
      showed bidirectional and saltatory movement with a bias towards one direction.
      Such vectorial movement was largely blocked by the dynein motor inhibitor EH NA
      (erythro-9-[3-(2-hydroxynonyl)] adenine), suggesting that the autophagosomes
      moved towards the soma, where most lysosomes are located. Interestingly, the
      application of the glutamate analog N-methyl-D-aspartic acid (NMDA) as an
      excitotoxin increased the number of autophagosomes in axons, while it did not
      significantly change its movement characteristics. These results suggest that
      autophagosomes play important roles in axons and are dynamically regulated under
      physiological and pathological conditions.

PMID- 20150764
TI  - Expression of miR-122 mediated by adenoviral vector induces apoptosis and cell
      cycle arrest of cancer cells.
AB  - BACKGROUND: microRNA-122 (miR-122) plays an important role in both of hepatic
      physiology and pathology. Downregulation of miR-122 was reported in human primary
      hepatocellular carcinoma (HCC) and restoration of miR-122 could suppress the
      growth of cancer cells. In this study, we presented a novel strategy for cancer
      therapy based on gene transfer of miR-122 by adenoviral vector. METHODS: We
      generated a recombinant adenoviral vector expressing miR-122 (Ad-miR122). The miR
      122 expression was measured by quantitative Real-Time PCR (qRT-PCR). Cell
      survival rate was determined by MTT assay. RESULTS: Our data showed that Ad
      miR122 could express functional miR-122 in tumor cells at a high level. Infection
      of tumor cells with Ad-miR122 resulted in inhibition of growth of cancer cells
      originating from liver (HepG2, Hep3B, Huh7 and PLC/PRF/5), lung (NCI-H460) and
      uterine cervix (HeLa). This antitumor activity was related to the induction of
      apoptosis and/or cell cycle arrest in cancer cells. Infection with Ad-miR122
      resulted in decreased expression of Bcl-W and CCNG1 in cancer cells. CONCLUSION:
      The antitumor activity of Ad-miR122 was probably due to the induction of
      apoptosis and/or cell cycle arrest in cancer cells through inhibiting Bcl-W
      and/or CCNG1 expression. We concluded that expression of therapeutic microRNA,
      such as miR-122, via adenoviral vector is a promising strategy for cancer
      treatment.

PMID- 20150765
TI  - GammaH2AX as a molecular marker of aging and disease.
AB  - Double-strand breaks are one of the most critical DNA lesions with respect to
      cell-death and preservation of genomic integrity. Rapid phosphorylation of the
      histone variant H2AX at Ser-139 to form gammaH2AX is an early cellular response
      to DNA double-strand breaks. Visualization of discrete gammaH2AX foci using
      immunofluorescence-based assays has provided a sensitive and effective method for
      detecting DSBs which may be implicated in various pathologies including cancer,
      age-related diseases, chronic inflammatory diseases and ischemia-reperfusion
      injury. In this review, the potential utility and significance of gammaH2AX as a
      molecular marker of aging and disease is analysed.

PMID- 20150766
TI  - Antibody immunosuppressive therapy in solid-organ transplant: Part I.
AB  - Currently, a wide variety of both polyclonal and monoclonal antibodies are being
      routinely utilized to prevent and treat solid organ rejection. More commonly,
      these agents are also administered in order to delay introduction of calcineurin
      inhibitors, especially in patients with already compromised renal function. While
      these antibody therapies dramatically reduced the incidence of acute rejection
      episodes and improved both short and long-term graft survival, they are also
      associated with an increased incidence of opportunistic infections and neoplastic
      complications. Therefore, effective patient management must necessarily balance
      these risks against the potential benefits of the therapy.

PMID- 20150767
TI  - Engineered Fc variant antibodies with enhanced ability to recruit complement and
      mediate effector functions.
AB  - Engineering the antibody Fc region to enhance the cytotoxic activity of
      therapeutic antibodies is currently an active area of investigation. The
      contribution of complement to the mechanism of action of some antibodies that
      target cancers and pathogens makes a compelling case for its optimization. Here
      we describe the generation of a series of Fc variants with enhanced ability to
      recruit complement. Variants enhanced the cytotoxic potency of an anti-CD20
      antibody up to 23-fold against tumor cells in CDC assays, and demonstrated a
      correlated increase in C1q binding affinity. Complement-enhancing substitutions
      combined additively, and in one case synergistically, with substitutions
      previously engineered for improved binding to Fc gamma receptors. The engineered
      combinations provided a range of effector function activities, including
      simultaneously enhanced CDC, ADCC, and phagocytosis. Variants were also effective
      at boosting the effector function of antibodies targeting the antigens CD40 and
      CD19, in the former case enhancing CDC over 600-fold, and in the latter case
      imparting complement-mediated activity onto an IgG1 antibody that was otherwise
      incapable of it. This work expands the toolkit of modifications for generating
      monoclonal antibodies with improved therapeutic potential and enables the
      exploration of optimized synergy between Fc gamma receptors and complement
      pathways for the destruction of tumors and infectious pathogens.

PMID- 20150768
TI  - Targeting the endothelin receptor in prostate cancer bone metastasis: Back to the
      mouse?

PMID- 20150769
TI  - Elevated Beclin 1 expression is correlated with HIF-1alpha in predicting poor
      prognosis of nasopharyngeal carcinoma.
AB  - Recent studies have suggested that autophagy plays a pivotal role in regulation
      of cancer development and progression. High expression of the autophagy-related
      Beclin 1 protein predicted favorable patient outcome in several tumors. Here, a
      randomized controlled trial (RCT)-derived 128 nasopharyngeal carcinoma (NPC)
      patients were subjected to analysis of Beclin 1 expression and survival
      probability. In this RCT, 61 patients treated with induction chemotherapy plus
      concurrent chemoradiotherapy were used as a training set to generate a Beclin 1
      cutoff score for patient outcome by receiver operating characteristic (ROC) curve
      analysis. For validation, the ROC-derived cutoff point was subjected to analysis
      of the association of Beclin 1 expression with patient outcome and clinical
      characteristics in testing set. The testing set comprised of 67 patients received
      induction chemotherapy plus radiotherapy. In the testing set and overall
      patients, our univariate and multivariate analysis showed that higher Beclin 1
      expression, defined by the training set ROC analysis-generated cutoff score,
      predicted poorer overall survival, progression-free survival and distant
      metastasis-free survival. However, we failed to detect a correlation between
      Beclin 1 and local failure-free survival. Moreover, a positive relationship
      between Beclin 1 and HI F-1alpha expression was found. Importantly, among
      patients with elevated HI F-1alpha expression, a subset with lower Beclin 1
      expression displayed a significant overall survival advantage than those with
      higher expression (p = 0.036). Contrary to previous studies, our results
      demonstrated that high autophagic Beclin 1 expression was an inferior prognostic
      marker for NPC. HI F-1alpha-associated Beclin 1 high expression might facilitate
      NPC cells surviving from chemoradiotherapy, suggesting a novel therapeutic
      molecular target for NPC.

PMID- 20150770
TI  - Enhanced acute apoptotic response to azoxymethane-induced DNA damage in the
      rodent colonic epithelium by Tyrian purple precursors: a potential colorectal
      cancer chemopreventative.
AB  - Colorectal cancer (CRC) is the second most prevalent and deadly cancer worldwide.
      Due to the mortality and morbidity associated with chemotherapeutic regimes,
      research is turning to natural product enhancement of the acute apoptotic
      response to genotoxic carcinogens (AARGC). Although Tyrian purple dye pigments
      and precursors from muricid molluscs are known for their anti-proliferative and
      proapoptotic activity, the chemoprotective properties of these edible molluscs
      has not been assessed. Enhancement of AARGC by oral administration of muricid
      extract (ME), containing a mixture of the cytotoxins tyrindoleninone and 6
      bromoisatin, was assessed in an azoxymethane (AOM) rodent model. A dose-dependent
      increase in apoptotic index was observed in the distal colon, with a significant
      increase detected at an ME dose of 1.0 mg/g (p < 0.01). Proliferation (PCNA)
      index failed to vary significantly at this ME concentration, which confirms the
      ME-induced increase in apoptotic response to DNA alkylation. ME also appears to
      confer no major toxic side effects, as all mice consistently gained weight during
      the trial and colonic crypt height was maintained (p > 0.05) independent of ME
      dose. Although, this is the first example of AARGC enhancement by indole-based
      compounds, bioactive precursor degradation in simulated gastric fluid may prevent
      introduction of muricids as a chemopreventative food. Nevertheless, the
      protective effect of ME against CRC in vivo clearly substantiates further
      research into the chemopreventative efficacy of Muricidae natural products.

PMID- 20150771
TI  - Learning the art of critical debate.

PMID- 20150774
TI  - Development of macrosomia resulting from gestational diabetes mellitus:
      physiology and social determinants of health.
AB  - This integrative review sought to advance understanding of the literature
      pertaining to gestational diabetes mellitus (GDM) and subsequent lifestyle
      changes in Canadian and American populations. Gestational diabetes mellitus
      includes glucose intolerance identified during pregnancy and affects
      approximately 7% of all pregnancies worldwide or more than 200,000 cases
      annually. Depending upon the population studied and the diagnostic tests
      employed, the prevalence may range from 1% to 14% of all pregnancies. The article
      comprises 2 parts in which internal and external factors are discussed concerning
      pathophysiologic pathways and psychosocial influences. Social determinants of
      health affect the development of GDM. Gestational diabetes mellitus is increasing
      in all socioeconomic strata, particularly because of stress, sedentary lifestyle,
      and poor nutritional choices. Questions are raised about future research
      directions.

PMID- 20150775
TI  - Exposure to maternal voice in preterm infants: a review.
AB  - The mother's voice, along with other developmentally appropriate sensory events
      (ie, touch, light, smells), stimulates maturation of the sensory systems and
      helps shape normal fetal development. While vast changes in the neonatal
      intensive care unit have occurred over the last 2 decades, little research has
      addressed the loss of exposure to maternal voice for the preterm infant. To
      address this gap, we compared studies that directly investigated effects of
      exposure to maternal voice on preterm infants. Studies reviewed were conducted
      between 1972 and 2007. All presented recordings of maternal voice at sound levels
      above current recommendations, and few of the findings reached statistical
      significance. Some potentially positive developmental effects were indicated.
      Future study of the effects of exposure to maternal voice on preterm infants
      using recommended sound levels is needed.

PMID- 20150777
TI  - A case study on Walker-Warburg syndrome.
AB  - Walker-Warburg syndrome (WWS) is a rare, lethal genetic disease associated with a
      cobblestone-type lissencephaly, eye abnormalities, and a type of muscular
      dystrophy. There is a wide spectrum of brain and eye defects associated with this
      diagnosis; therefore, this diagnosis may not initially be considered. This
      diagnosis is especially difficult for families because there is no treatment
      available and management of the condition is supportive only. Parents of an
      infant with WWS need to be shown support and empathy while they are dealing with
      the sorrow of a terminal illness. Use of a nursing model, "Middle range theory of
      chronic sorrow," will be instrumental in assisting staff as they care for the
      patient and the patient's family. They also need to be guided toward receiving
      genetic counseling to weigh their options for future family planning as the risk
      of another WWS pregnancy is 25%.

PMID- 20150779
TI  - Trisomy 18 and choices.

PMID- 20150778
TI  - Neonatal experiences of newborns with full trisomy 18.
AB  - PURPOSE: To provide information about neonatal experiences for newborns with full
      trisomy 18 (t18). SUBJECTS: Mothers of 21 newborns with full t18 (13 survivors; 8
      who died prior to mothers' participation in the study). DESIGN: Mixed method,
      descriptive, online survey. METHODS: Subjects completed an online survey. Data
      were downloaded into an SPSS database. Descriptive statistics were used to
      analyze resulting data. MAIN OUTCOME MEASURES: Subjects' responses on Tracking
      Rare Incidence Syndromes survey. PRINCIPAL RESULTS: Newborns presented with
      syndrome-related physical characteristics (eg, low-set ears, small jaw) and
      medical conditions (eg, heart defects). Gestational age was generally older than
      what is described in the existent literature. In the NICU, newborns were provided
      with a variety of equipments (eg, nasal cannula, pulse oximeter) and received
      treatments including blood transfusions and echocardiograms. Data also indicate
      longer survival rates (103.3 months for survivors, 37.5 months for nonsurvivors)
      than that described in the literature. CONCLUSIONS: Data indicate presence of
      common presenting physical and medical characteristics and varied medical
      assistance to newborns with full t18.

PMID- 20150780
TI  - Influence of test weighing before/after nursing on breastfeeding in preterm
      infants.
AB  - PURPOSE: Swedish hospitals apply various regimens for preterm infants' nutrition
      in connection with their mothers' establishment of breastfeeding. Milk intake is
      assessed either by test weighing before and after breastfeeding or by observing
      the infant's suckling behavior (ie, clinical indices). These differing policies
      may lead to differences in infants' feeding progress. The purpose of this study
      was to compare effects on breastfeeding and weight gain of preterm infants,
      depending on whether the volume of breast milk intake when suckled in the
      hospital was estimated by "clinical indices" or determined by test weighing.
      SUBJECTS: Sixty-four infants treated at a unit applying test weighing were
      compared with 59 infants treated at a unit assessing milk intake by "clinical
      indices." DESIGN AND METHODS: A retrospective, descriptive, and comparative
      design was used to explore the consequences of different nutrition regimens. Data
      were obtained from a review of hospital medical records. PRINCIPAL RESULTS: The
      infants treated at the hospital where test weighing was practiced attained
      exclusive breastfeeding at an earlier postmenstrual age (PMA) and were also
      discharged at an earlier PMA. However, the 2 study units were alike regarding the
      proportion of infants attaining exclusive breastfeeding, the postnatal age when
      this occurred, and the weight pattern in hospital. CONCLUSION: To establish
      breastfeeding in preterm infants, test weighing before and after breastfeeding
      and gradual reduction of supplementation are both applicable regimens. Mothers
      can be encouraged to choose either of them, although test weighing may help
      infants attain exclusive breastfeeding at an earlier PMA.

PMID- 20150781
TI  - Evidence-based practice brief: promoting breastfeeding in the NICU.

PMID- 20150782
TI  - Educational preparation for nursing practice roles.

PMID- 20150783
TI  - Bibliography-Editors' selection of current world literature.

PMID- 20150784
TI  - State health department structure and pandemic planning.
AB  - Pandemic influenza is an imminent threat, with the April/May 2009 A(H1N1)
      outbreak as a testament to the potential for rapid transmission and spread of a
      novel influenza strain. Research has shown that there are great disparities in
      state pandemic planning; however, little work has been done to assess how health
      department structure impacts pandemic preparedness. The purpose of this article
      was to examine the impact of state health department structure on state pandemic
      influenza plan integration of federal recommendations. The study consisted of a
      cross-sectional analysis of 41 states and found that structural and strategy
      making variables have the greatest impact on pandemic plan inclusion of federal
      recommendations. Strong, multilayered health department hierarchies and the
      tenure of senior staff are negatively associated with preparedness, whereas
      professionalization is positively associated with pandemic plan
      comprehensiveness. State health departments can take minimally invasive steps to
      increase their effectiveness in pandemic preparedness by reducing layers of
      bureaucracy and increasing training for staff.

PMID- 20150785
TI  - Local public health departments in California: changing nutrition and physical
      activity environments for obesity prevention.
AB  - The purpose of this research was to assess California public health departments
      capacity, practices, and resources for changing nutrition and physical activity
      environments for obesity prevention. The researchers surveyed key public health
      department personnel representing all 61 health departments in California using a
      Web-based survey tool. The response rate for the survey was 62 percent. This
      represented a 93 percent health department response rate. Analysis was conducted
      on the individual respondent and public health department levels and stratified
      by metropolitan statistical area and foundation-funded versus not foundation
      funded. Public health departments are engaged in obesity prevention including
      environmental and policy change approaches. The majority of respondents stated
      that monitoring obesity rates and providing leadership for obesity prevention are
      important roles for public health. Health departments are involved in advocacy
      for healthier eating and/or physical activity in school environments and the
      development and monitoring of city/county policies to improve the food and/or
      physical activity environments. Funding and staff skill may influence the degree
      of public health department engagement in obesity prevention. A majority of
      respondents rate their staffing capacity for improving nutrition and physical
      activity environments as inadequate. Access to flexible foundation funding may
      influence how public health departments engage in obesity prevention.

PMID- 20150786
TI  - Relationships between local public health agency functions and agency leadership
      and staffing: a look at nurses.
AB  - The United States is facing a severe shortage of well-trained public health
      workers, and public health nursing is the discipline with the greatest shortage.
      A local public health agency's (LPHA's) staffing and leadership characteristics
      are critical in determining its programs, performance, and capacity. A better
      understanding of the relationship between specific staffing and leadership
      characteristics and public health programs is needed to address this capacity
      challenge. METHOD: Data from the 2005 National Profile of Local Health
      Departments, were examined to identify associations between an LPHA's nursing
      workforce and the specific activities performed by LPHAs. RESULTS: LPHAs with a
      nurse as senior executive had a greater breadth of immunization, maternal/child
      health, and prevention activities than their nonnurse-led counterpart LPHAs,
      particularly in rural areas. Nurse-led LPHAs were less likely, however, to have a
      broad level of environmental health and regulation activities or to have recently
      conducted community assessment and planning activities. CONCLUSIONS: Both LPHA
      nurse leaders and nursing staff play an important role in the provision of LPHA
      services, and a shortage of LPHA nursing leaders and staff, particularly in rural
      areas, will likely have a major impact on certain LPHA programs unless steps are
      taken to address these challenges.

PMID- 20150787
TI  - Leading and managing for improved health.

PMID- 20150788
TI  - Self-assessment of public health essential services among Illinois local health
      department administrators.
AB  - This article uses data from a study commissioned by the Illinois Public Health
      Institute in 2007 as part of the Robert Wood Johnson Foundation Multistate
      Learning Collaborative Grant for exploring accreditation of health departments.
      Local health departments in Illinois were surveyed on their self-assessed
      performance in meeting a set of performance standards derived from the Illinois
      Practice Standards and the Operational Definition of a Functional Local Health
      Department. All state-certified local health departments were represented in the
      survey by the 81 respondents. The lowest scores were observed in the evaluate
      standard (evaluate programs and provide quality assurance in accordance with
      applicable professional and regulatory standards to ensure that programs are
      consistent with plans and policies, and provide feedback on inadequacies and
      changes needed to redirect programs and resources). The findings suggest that new
      approaches are needed to better integrate evaluation in local health departments
      beginning with training designed specifically for and informed by local health
      department administrators.

PMID- 20150790
TI  - Business process improvement: an electronic system to monitor compliance with
      medical resident work hours.
AB  - The limitation of medical intern and resident work hours, known as the Bell 405
      regulations, was initiated in New York State in 1989 with a modification to the
      state hospital code. The Bell 405 regulations were strengthened in 2000, and
      facilities would now be fined for noncompliance. Monitoring systems in place at
      that time were insufficient to provide an adequate level of review for the New
      York City Health and Hospitals Corporation (HHC) with more than 7,000 medical
      residents whose training is based at or who rotate through these public
      hospitals. A "simple to use," yet comprehensive, method of monitoring compliance
      needed to be developed to ensure that residents and interns complied with laws
      regulating working hours. The subsequent development of national accreditation
      standards increased the stakes for reliable scrutiny. HHC developed and
      implemented a Web-based Structured Query Language (SQL) application that
      facilitated easy access to work hour surveys captured through electronic time
      sheets. The time sheet data automatically entered a database that provided
      instant analysis of conformance to state law. The development of an electronic on
      line application accessible from anywhere allowed HHC to efficiently identify
      nonconformance and pinpoint corrective action. Since the inception of the
      application and its expansion allowing access through the intranet, 26,000
      individual time sheets have been submitted for evaluation. With the national
      movement regulating work hours, other hospitals still at the pencil and manual
      computation stage would greatly benefit by developing a similar application.

PMID- 20150789
TI  - Decision science: a scientific approach to enhance public health budgeting.
AB  - The allocation of resources for public health programming is a complicated and
      daunting responsibility. Financial decision-making processes within public health
      agencies are especially difficult when not supported with techniques for
      prioritizing and ranking alternatives. This article presents a case study of a
      decision analysis software model that was applied to the process of identifying
      funding priorities for public health services in the Spokane Regional Health
      District. Results on the use of this decision support system provide insights
      into how decision science models, which have been used for decades in business
      and industry, can be successfully applied to public health budgeting as a means
      of strengthening agency financial management processes.

PMID- 20150791
TI  - New data, same story? Revisiting studies on the relationship of local public
      health systems characteristics to public health performance.
AB  - This study examined the relationship between community and system characteristics
      of 353 local public health agencies and local public health system performance by
      revisiting previous research by Mays et al and Scutchfield et al. More recent and
      coterminous data were used. Local public health agency characteristics were
      obtained from the National Association of City and County Health Officials' 2005
      National Profile of Local Public Health Departments and performance data were
      obtained from version 1 of the National Public Health Performance Standards
      Program local performance assessment instrument. Descriptive analyses and
      multivariate analyses similar to the two previous studies were employed.
      Population size, presence of a local board of health and whether the board makes
      policy, educational background of the local public health agency's top executive,
      and jurisdiction type were found to be important predictors of local public
      health performance. These findings support some of the earlier findings but do
      not support all the findings of the earlier studies. Variances are discussed.
      This study provides researchers and practitioners with an evidence base from
      which to make suggestions regarding characteristics, many changeable, which may
      influence system performance.

PMID- 20150792
TI  - Tool kits and maps for public health administrators.

PMID- 20150793
TI  - The survive and thrive program: encouraging coaching, mentoring, and peer
      learning among new local health officials.
AB  - There is a need for programs tailored to train the approximately 300 new local
      health officials (LHOs) who emerge each year with the knowledge and skills needed
      to build, maintain, and enhance public health capacity and infrastructure. The
      Survive and Thrive program incorporates a curriculum that is designed to address
      the challenges faced by a new LHO. The Survive and Thrive program seeks to
      address these issues by leveraging the expertise of the current generation of
      local public health leadership by incorporating experienced LHOs as coaches.
      Coaching, mentoring, and peer assistance by seasoned LHOs is critical to these
      new learning opportunities. This article highlights aspects of the coaching
      component of Survive and Thrive program. Actual examples of its relevance to the
      professional growth and development of new LHOs and the coaches themselves are
      presented. The article also describes the novel approach of including coaches in
      evaluating program effectiveness. The Survive and Thrive program's coaching
      component can serve as a template for other public health leadership programs and
      related workforce development initiatives as well as a model to help facilitate
      lifelong learning of LHOs.

PMID- 20150794
TI  - Potential approaches to address the undergraduate public health training needs
      for working professionals: a case study of one rural area.
AB  - The leadership of several health districts in the rural Appalachian region of
      northeast Tennessee and southwest Virginia has expressed interest in addressing
      the educational needs of their employees. The majority of these workers have not
      completed an undergraduate degree, but they desire to further their education.
      The College of Public Health at East Tennessee State University has begun
      preliminary discussions with these leaders to identify potential approaches to
      address these needs. There appear to be four approaches that should be explored
      by regions facing similar challenges: on-line or on-line/on-site degree
      completion programs; course clusters provided for academic credit; partnerships
      with community colleges; and training programs offered for nonacademic credit.

PMID- 20150795
TI  - Improving knowledge of public health accreditation through a group vetting
      session of a practice-based research network.
AB  - This article describes efforts to improve knowledge of and acceptance of the
      proposed voluntary health department accreditation program, put forth by Public
      Health Accreditation Board (PHAB), by conducting a group vetting session. The
      vetting session closely followed the PHAB guidelines, and participants received
      pre- and postvetting surveys to gauge their knowledge of the accreditation
      standards and related items and their perception of the utility of the standards
      and the ability of their agencies to meet the standards. Respondents reported
      that the vetting session did improve their knowledge and understanding of the
      standards (increase in mean score from 3.6 to 4.4). In addition, respondents had
      overwhelmingly favorable responses to the draft standards (28 of 31 received
      positive responses from more than 85% of participants). This suggests that
      conducting group vetting sessions may be an effective way to increase awareness
      of the PHAB standards and may help prepare local health agencies for the
      accreditation process.

PMID- 20150796
TI  - Local health department priority setting: an exploratory study.
AB  - Priority setting is an integral part of the community health assessment process
      since it helps direct the allocation of limited public health resources among
      competing needs. There is a recognized need for a systematic mechanism to
      prioritize community health issues in objective, data-driven, quantifiable
      measures. This exploratory study examined the extent to which data-driven
      objective criteria were considered important to public health officials in North
      Carolina and, specifically, the extent to which they chose between objective and
      subjective criteria in establishing public health priorities. The differences
      between the health officers' practice (criteria they actually used) and their
      preferences (criteria thought to be important) were also assessed. It was found
      that NC health directors generally used subjective criteria more often than
      objective criteria when deciding on the most important health issues in their
      communities. A considerable segment of the respondents, however, considered
      objective criteria more important, even though subjective criteria were the
      dominant influence in their actual practice of priority setting. Our preliminary
      results suggest that officers' education and tenure may influence their practice
      and preferences. Perceived and real barriers to the use of data-driven objective
      criteria for priority setting are an important topic for future public health
      research.

PMID- 20150797
TI  - Public health administration and science: strange bedfellows?

PMID- 20150798
TI  - Lessons learned in systems thinking approach for evaluation planning.
AB  - The role of systems thinking is addressed in the context of a public health
      department-academic collaboration to plan the evaluation of a learning management
      system. Findings suggest new directions for public health practitioners and
      researchers who are responsible for ensuring that public health workforce
      training efforts, and other programs and services, have the intended impact on
      public health workers' competence and the public's health.

PMID- 20150799
TI  - Practical and affordable ways to cultivate leadership in your organization.
AB  - Leadership can be cultivated through the intentional actions of managers and
      others in public health organizations. This article provides a rationale for
      taking innovative and proactive steps to build leadership, discusses four general
      strategies for doing so, and presents seven practical, creative, and affordable
      actions that can have a positive influence on efforts to cultivate leadership
      qualities in the public health workforce. Each action is illustrated with an
      actual contemporary example from a local public health agency. The actions
      include providing formal or informal coaching/mentoring opportunities; assigning
      staff to lead new projects or collaborations, projects outside their disciplines,
      projects that cause growth in their information technology capacity, or orphan or
      struggling projects; facilitating a book club; and institutionalizing reflection.
      The best way to ensure that effective leadership is available when the
      organization needs it is to intentionally develop it through an ongoing process.
      Leadership growth can be supported during the ordinary course of business in a
      public health organization through thoughtful challenges, sharing ideas and
      experiences, and especially through the example set by managers and those in
      positions of authority.

PMID- 20150800
TI  - Adapting the "managing by walking around" methodology as a leadership strategy to
      communicate a hospital-wide strategic plan.
AB  - Metropolitan Hospital Center (MHC) in East Harlem, New York, has undergone
      significant leadership changes within the past few years, and the current
      leadership team developed a long-term strategic plan for the organization that it
      wanted to effectively communicate to all hospital staff. The spread of
      information is a challenge at MHC, as it is in many hospitals, because of the
      large number of staff working various shifts, and the inability of staff to leave
      their units at the same time to attend general staff meetings. Because of the
      recent success of the hospital's Executive WalkRounds Program and Breakthough
      Program, which embody principles of the leadership strategy Managing By Walking
      Around (MBWA), the senior leadership team decided to roll out their new strategic
      plan in a 2-week series of rounds to each unit/department throughout the hospital
      during each shift. Utilizing this method, 69 percent of MHC staff attended the
      rounds, and 88.9 percent of management level staff and 64.5 percent of
      unionized/labor who participated in the hospital's Employee Satisfaction Survey
      stated that they understood the hospital's new strategic plan. MHC's successful
      strategy is easily applicable within other similar settings.

PMID- 20150801
TI  - Understanding and managing organizational change: implications for public health
      management.
AB  - Managing organizational change has become a significant responsibility of
      managers. Managing the change process within public health organizations is
      important because appropriately and systematically managing change is linked to
      improved organizational performance. However, change is difficult and the change
      process poses formidable challenges for managers. Managers themselves face
      increased pressure to respond to environmental influences and provide the
      necessary leadership to their organizations in the change process. In fact,
      managing organizational change has become a key competency for healthcare
      managers. This article addresses the important topic of organizational change in
      public health organizations. It provides a conceptual foundation for
      understanding organizational change and its relationship to healthcare
      organizational performance, and then discusses the types and nature of change,
      using some examples and evidence from those organizations that have successfully
      managed change. A framework for guiding public health managers in the change
      management process is provided. The article concludes with suggested management
      competencies to establish a change-oriented organization with the culture and
      capacity for change.

PMID- 20150802
TI  - Management and leadership.

PMID- 20150803
TI  - Increasing local health department capacity to improve the health of people with
      disabilities.
AB  - The National Association of County and City Health Officials (NACCHO) is the
      national organization representing local health departments. It supports efforts
      that protect and improve the health of all people and all communities by
      promoting national policy, developing resources and programs, seeking health
      equity, and supporting effective local public health practice and systems.

PMID- 20150804
TI  - Iatrogenic botulism after botulinum toxin type A injections.
AB  - Therapeutic use of botulinum toxin type A (BT/A) is well known, effective, and
      safe. Iatrogenic botulism that presents with generalized weakness, dysphagia, and
      respiratory distress is a rare but significant complication in BT/A treatment. In
      this study, we report 4 patients who developed iatrogenic botulism after
      receiving therapeutic doses of BT/A for spasticity and blepharospasm. One patient
      was placed in intensive care unit, but consequently, every patient recovered
      fully. The cause of BT/A as an adverse effect is most likely hematological spread
      of the toxin.

PMID- 20150805
TI  - The impact of vitamin D deficiency on diabetes and cardiovascular risk.
AB  - PURPOSE OF REVIEW: To review the association between vitamin D deficiency and
      diabetes and cardiovascular risk. RECENT FINDINGS: Vitamin D deficiency is newly
      recognized as a common condition of increasing prevalence worldwide. Clinically,
      vitamin D has an established role in calcium and bone metabolism and has recently
      been shown to be associated with increased risk of developing type 1 and type 2
      diabetes mellitus and cardiovascular disease (CVD), as well as with
      cardiovascular risk factors such as hypertension and obesity. The molecular
      mechanisms of these associations remain incompletely understood. The active
      metabolite of vitamin D regulates transcription of multiple gene products with
      antiproliferative, prodifferentiative, and immunomodulatory effects. Although
      vitamin D deficiency is frequently unrecognized clinically, laboratory
      measurement is easy to perform and treatment of vitamin D deficiency is
      relatively well tolerated and inexpensive. Limited, yet promising, results of
      proof-of-concept intervention studies of using vitamin D in diabetes will be
      presented. SUMMARY: The high prevalence of vitamin D deficiency and plausible
      molecular mechanisms linking this to diabetes and cardiovascular risk suggest
      treatment of vitamin D deficiency to prevent and/or treat diabetes is a promising
      field to explore.

PMID- 20150808
TI  - Bladder cancer.
AB  - PURPOSE OF REVIEW: To review the diagnosis and management of all stages of
      bladder cancer with an emphasis on studies and developments within the last year.
      RECENT FINDINGS: Cystoscopy remains the gold standard for diagnosis of bladder
      tumors, though fluorescent light and urinary biomarkers can both improve the
      sensitivity of cancer detection. Management of high-risk patients with nonmuscle
      invasive cancer continues to be controversial, with a number of risk assessment
      tools developed to help stratify patients to cystectomy or bladder-sparing
      regimens. Intravesical therapy is utilized both as a one-time perioperative
      regimen and as a weekly regimen, and research continues in the development of
      agents for bacillus Calmette-Guerin-refractory superficial bladder cancer. In
      patients undergoing cystectomy, evidence supports the need for an adequate
      lymphadenectomy. Although there are limited data on robotic assisted radical
      cystectomy, initial reports suggest that an appropriate lymph node dissection can
      be performed. The role of bladder-sparing modalities as well as the use of
      adjuvant and neoadjuvant therapies is still debated. Trials investigating these
      therapies continue to seek to improve both oncologic outcomes and quality of life
      for patients with invasive bladder cancer. SUMMARY: Progress continues in bladder
      cancer diagnosis and management, and we anticipate that future work will further
      advance the care of patients with this disease.

PMID- 20150806
TI  - Humanized mouse models to study human diseases.
AB  - PURPOSE OF REVIEW: Update on humanized mouse models and their use in biomedical
      research. RECENT FINDINGS: The recent description of immunodeficient mice bearing
      a mutated IL-2 receptor gamma chain (IL2rgamma) facilitated greatly the
      engraftment and function of human hematolymphoid cells and other cells and
      tissues. These mice permit the development of human immune systems, including
      functional T and B cells, following engraftment of hematopoietic stem cells
      (HSCs). The engrafted functional human immune systems are capable of T and B cell
      dependent immune responses, antibody production, antiviral responses, and
      allograft rejection. Immunodeficient IL2rgamma(null) mice also support heightened
      engraftment of primary human cancers and malignant progenitor cells, permitting
      in-vivo investigation of pathogenesis and function. In addition, human-specific
      infectious agents for which animal models were previously unavailable can now be
      studied in vivo using these new-generation humanized mice. SUMMARY:
      Immunodeficient mice bearing an IL2rgamma(null) mutated gene can be engrafted
      with functional human cells and tissues, including human immune systems,
      following engraftment with human hematolymphoid cells. These mice are now used as
      in-vivo models to study human hematopoiesis, immunity, regeneration, stem cell
      function, cancer, and human-specific infectious agents without putting patients
      at risk.

PMID- 20150807
TI  - MicroRNAs in atherosclerosis and lipoprotein metabolism.
AB  - PURPOSE OF REVIEW: MicroRNAs (miRNA) are mediators of post-transcriptional gene
      expression that likely regulate most biological pathways and networks. The study
      of miRNAs is a rapidly emerging field; recent findings have revealed a
      significant role for miRNAs in atherosclerosis and lipoprotein metabolism, which
      will be described in this review. RECENT FINDINGS: The discovery of miRNA gene
      regulatory mechanisms contributing to endothelial integrity, macrophage
      inflammatory response to atherogenic lipids, vascular smooth muscle-cell
      proliferation, and cholesterol synthesis are described. Furthermore, recent
      evidence suggests that miRNAs may play a role in mediating the beneficial
      pleiotropic effects observed with statin-based lipid-lowering therapies. New
      modifications to miRNA mimetics and inhibitors, increasing targeting efficacy and
      cellular uptake, will likely enable future therapies to exploit miRNA gene
      regulatory networks. SUMMARY: At this time, the applicability and full potential
      of miRNAs in clinical practice is unknown. Nonetheless, recent advances in miRNA
      delivery and inhibition hold great promise of a tremendous clinical impact in
      atherosclerosis and cholesterol regulation.

PMID- 20150809
TI  - Advances in penile cancer management.
AB  - PURPOSE OF REVIEW: Penile cancer is a rare disease that may cause devastating
      physical and psychological effects on patients due to the disease itself and/or
      the associated treatments. As with many other cancer types, significant efforts
      have been made in penile cancer to minimize invasiveness and morbidity of
      therapeutic approaches, while aiming to conserve organ function and optimize
      disease control. This updated review focuses on penile cancer management data
      published in the last few years. RECENT FINDINGS: Several aspects of penile
      cancer management are discussed in this review. Wider knowledge about the
      disease's natural history has provided the basis for new TNM staging and follow
      up schedule proposals. Modern imaging techniques and gene profiling assays have
      been applied. A new guideline addressing various aspects of penile cancer was
      recently published, and more extensive experience has been gained with sentinel
      lymph node biopsy and radiotherapy. Quality of life and psychosexual impact of
      the disease are also being addressed. SUMMARY: New diagnostic and therapeutic
      techniques, as well as attempts to better identify patients who may benefit from
      less invasive treatments have been studied, but more experience in the field is
      clearly needed. For this purpose, collaborative multicenter studies are strongly
      encouraged.

PMID- 20150810
TI  - Design and performance of clinical trials in head and neck cancer.

PMID- 20150811
TI  - 'Image and treat': an individualized approach to urological tumors.
AB  - PURPOSE OF REVIEW: The current treatment options for advanced urologic cancers
      demonstrate limited efficacy. To obtain optimal clinical results, there is a need
      for new, individualized, therapeutic strategies, which have only recently been
      applied to these malignancies. Nuclear medicine plays an important role in
      establishing imaging biomarkers necessary for personalized medicine. This review
      focuses on the current status of the 'image and treat' approach combining
      molecular imaging with targeted radionuclide therapy of urological malignancies
      RECENT FINDINGS: Tumor-specific targets in uro-oncology are showing promising
      results for development of personalized therapy using positron emission
      tomography/computed tomography (PET/CT) molecular imaging and radioimmunotherapy.
      The antibody cG250, which binds to carbonic anhydrase IX, is being evaluated as a
      radiolabeled imaging and therapeutic agent in clear-cell renal cell carcinoma. I
      cG250 PET/CT has demonstrated excellent targeting of clear-cell renal cell
      carcinoma. Prostate-specific membrane antigen is a promising target for both
      PET/CT and radioimmunotherapy of prostate cancer. HER2 may be another potential
      target in bladder and prostate cancer. SUMMARY: Tumor-specific targets and
      biomarkers are being studied for PET/CT and radioimmunotherapy. This may lead to
      development of new therapeutic strategies. However, considerable investment in
      new research will be required for personalized medicine to be routinely used in
      uro-oncology.

PMID- 20150812
TI  - Acute rheumatic fever and poststreptococcal reactive arthritis reconsidered.
AB  - PURPOSE OF REVIEW: The incidence of acute rheumatic fever (ARF) in the United
      States and Western Europe is decreasing and postStreptococcal reactive arthritis
      (PSRA) is more prevalent. It is not clear whether PSRA is a forme fruste of ARF
      or a separate disease entity. Therefore, this review explores similarities and
      dissimilarities in initial symptoms and signs, disease course and underlying
      pathophysiologic mechanisms. RECENT FINDINGS: ARF and PSRA present differently.
      PSRA patients are generally older, have a longer interval between group A
      streptococcus infection and symptom onset, and respond less dramatically to
      salicylates than ARF patients. The course of ARF may be complicated by carditis
      and valvular heart disease. Echocardiographic studies in Caucasian adults with
      PSRA have revealed no increase in valvular heart disease. The course of PSRA is
      characterized by arthritis that, in contrast to ARF, is additive, nonmigratory
      and is frequently chronic. Factors of the host, the Streptococcus and the immune
      response involved in the development of PSRA are scarcely explored, hampering
      comparisons with ARF. SUMMARY: On the basis of the differences in clinical
      presentation and disease course, ARF and PSRA are separate disease entities.
      Development of validated diagnostic criteria for PSRA is mandatory to proceed
      with studies on pathophysiological mechanisms and treatment in PSRA.

PMID- 20150813
TI  - Actual status of antiinterleukin-1 therapies in rheumatic diseases.
AB  - PURPOSE OF REVIEW: Several studies have evaluated the efficacy and safety of
      novel therapeutic options targeting interleukin-1 (IL-1), which not only plays a
      significant role in rheumatoid arthritis, but also in other rheumatic diseases,
      for which only limited therapeutical options exist. RECENT FINDINGS: Three
      different strategies have been pursued and evaluated in the past years:
      preventing IL-1 binding by occupying IL-1 receptors with anakinra, an imitation
      of the naturally occurring IL-1 receptor antagonist, anakinra; development of the
      fully human monoclonal anti-IL-1beta antibody canakinumab; and synthesis of the
      dimeric fusion protein rilonacept, consisting of the ligand-binding domain of
      interleukin-1 receptor type I and its accessory protein, bound to human IgG1.
      Each of these three anti-IL-1 agents proved efficacy in distinct clinical
      situations and disease entities. SUMMARY: Owing to the observation that IL-1 is
      not only involved in signaling processes resulting in autoimmune and crystal
      induced joint destruction but also in several hereditary autoinflammatory
      syndromes, its value both in pathophysiology as well as for novel advances in
      medication has significantly improved in the past years leading to an enrichment
      of the current therapeutic armamentarium for the affected patients.

PMID- 20150814
TI  - A comparison of the health status after percutaneous coronary intervention at a
      hospital with and without on-site cardiac surgical backup: a randomized trial in
      nonemergent patients.
AB  - BACKGROUND: Prospective randomized trials comparing the coronary artery disease
      related health status outcomes (changes in symptom grade, physical functional
      capacity and health-related quality of life) after percutaneous coronary
      intervention at hospitals with and without on-site cardiac surgical backup have
      not been reported earlier. METHODS: We randomly assigned 609 consecutive patients
      fulfilling pre-specified procedural low-risk criteria to undergo percutaneous
      coronary intervention at either a community hospital without or a regional
      hospital with on-site surgical backup. Five hundred and seventy-six patients
      completed the health status evaluation at baseline and at 6 months follow-up.
      RESULTS: At baseline, 91.4% had symptoms, and the mean (standard deviation)
      Canadian Cardiovascular Society's classification was 2.5 (0.9). The procedural
      success rates and the changes in health status measures were similar at the two
      hospitals. Overall there was a substantial relief of symptoms with a reduction in
      Canadian Cardiovascular Society's classification of 1.9 (1.2), increase in
      exercise time [1.4 (1.9) min] and reduction in use of antianginal drugs [0.6
      (0.9) less drugs] at follow-up compared with baseline (all P<0.001). Health
      related quality of life was evaluated with the Short-Form 36 health survey. There
      were significant and similar improvements in nearly all multi-item and summary
      scores from baseline to follow-up at the two hospitals. The largest improvements
      were seen in items related to physical functioning [overall change in Physical
      Component Score from baseline to follow-up 6.9 (9.1) points, P<0.001] and lowest
      in the mental health domains [change in Mental Component Score 3.3 (10.7) points,
      P<0.001]. INTERPRETATION: This study shows that a substantial and comparable gain
      in coronary artery disease-related health status can be achieved at hospitals
      both with and without surgical backup.

PMID- 20150815
TI  - The attendance of migrant women at the national breast cancer screening in the
      Netherlands 1997-2008.
AB  - The attendance of migrant women at the national breast cancer screening in the
      Netherlands is high; however, a much lower attendance was found in a study
      carried out in one region of the Netherlands some years ago. An increase in the
      attendance rates of migrant women over time was assumed, but no national data
      were available until now. The aim of this study is to provide national data about
      the attendance of migrant women at the national breast cancer screening in the
      Netherlands and the development of these attendance rates over time. The
      attendance rates at the national breast cancer screening program in the years
      1997-1998 and 2007-2008 of women of all nationalities are compared and the
      differences are tested with the chi test. The attendance of Dutch women at the
      breast cancer screening in 2007-2008 was high (83%). The attendance rates of
      migrant women originating from Africa, Asia or Latin America (63%), such as
      Turkish women (62%) and especially Moroccan women (54%), were significantly lower
      (P=0.00). Compared with 10 years before, the overall attendance in 2007-2008
      stayed almost constant, and changed only from 80 to 83%. The attendance rate of
      migrant women from Africa, Asia or Latin America increased from 51% in 1997-1998
      to 63% in 2007-2008. These national figures show that the attendance rates of
      migrant women at the breast cancer screening have increased substantially over
      the past 10 years. However, specific efforts to increase the attendance rates of
      this target group are needed because the current attendance rates of this group
      are still far below the overall attendance rates.

PMID- 20150816
TI  - Detection of hepatitis B virus covalently closed circular DNA in paraffin
      embedded and cryo-preserved liver biopsies of chronic hepatitis B patients.
AB  - BACKGROUND: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) may
      become an important predictor for treatment outcome or long-term follow-up. AIM:
      To detect cccDNA in formalin-fixed, paraffin embedded (FFPE) and to compare with
      cryo-preserved liver tissue. METHODS: Biopsies of 56 chronic hepatitis B patients
      were collected. Cryo-preserved and FFPE liver biopsies were available from 37 out
      of 56 patients. Paraffin was extracted with 1 ml xylene, followed by 100% alcohol
      and acetone. For the detection of cccDNA, selective primers were used. For
      quantification of hepatocytes a commercial Taqman beta-actin control kit was
      used. RESULTS: The cccDNA was detected in 80% of FFPE and in 100% of cryo
      preserved liver specimens. Recovery of hepatocytes and cccDNA was approximately a
      100-fold lower in FFPE liver tissue, but intrahepatic cccDNA levels were
      comparable. In FFPE and cryo-preserved liver tissue, intrahepatic cccDNA levels
      correlated strongly with HBV DNA, hepatitis B e antigen (HbeAg), and plasma
      cccDNA levels. HbeAg positive chronic hepatitis B patients had significantly
      higher intrahepatic cccDNA levels compared with HBeAg negative patients (P<0.05).
      In HBeAg positive patients, no difference in intrahepatic cccDNA levels were seen
      between patients with active (histological activity index score>3; HBV DNA>20 000
      IU/ml) and inactive hepatitis (histological activity index score</=3). In HBeAg
      negative chronic hepatitis B patients, intrahepatic cccDNA levels were
      significantly higher in patients with active hepatitis (P=0.004 and 0.001).
      CONCLUSION: Recovery of hepatocytes and cccDNA in FFPE tissue was lower, but
      intrahepatic cccDNA in FFPE biopsies were comparable with cryo-preserved liver
      tissue. Therefore, FFPE liver tissue is an attractive alternative for cccDNA
      analysis when cryo-preserved tissue is not available.

PMID- 20150817
TI  - Acute and chronic hemodynamic changes after propranolol in patients with
      cirrhosis under primary and secondary prophylaxis of variceal bleeding: a pilot
      study.
AB  - BACKGROUND AND AIM: Prophylactic treatment of variceal bleeding in cirrhotic
      patients with beta-blockers is effective in only some patients. Our aim was to
      determine whether the response of the hepatic venous pressure gradient (HVPG) to
      the intravenous administration of propranolol predicts the response after chronic
      oral propranolol treatment. PATIENTS AND METHODS: We included prospectively
      cirrhotic patients with esophageal varices under primary prophylaxis (PP) and
      secondary prophylaxis (SP). The HVPG was measured at baseline and after a
      propranolol bolus (0.15 mg/kg intravenous). A patient was considered a good
      responder if HVPG decreased to 12 mmHg or 20% from baseline. Patients then
      received oral propranolol (heart rate titrated). Poor-responders under SP were
      also included in a variceal band ligation program. After at least 3 months, a
      second hemodynamic study was conducted. RESULTS: Fifty-six patients were included
      (36 SP and 20 PP). Response rate was similar (32.1 and 41.9%, P=0.7) and the
      Pearson's correlation coefficient was 0.61 (P=0.001). In 81.4% patients, the
      first study predicted the response status of the second. Six patients rebled on
      follow-up between the studies, all of them were poor responders to intravenous
      propranolol. CONCLUSION: A single hemodynamic study using intravenous propranolol
      seems to predict chronic response to propranolol.

PMID- 20150818
TI  - The prevalence and clinical course of HIV-associated pulmonary cryptococcosis in
      Uganda.
AB  - BACKGROUND: The prevalence and clinical course of pulmonary cryptococcosis in Sub
      Saharan Africa are not well described. METHODS: Consecutive HIV-infected adults
      hospitalized at Mulago Hospital (Kampala, Uganda) between September 2007 and July
      2008 with cough >or=2 weeks were enrolled. Patients with negative sputum smears
      for acid-fast bacilli were referred for bronchoscopy with bronchoalveolar lavage
      (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii, and
      fungi. Patients were followed 2 and 6 months after hospital discharge. RESULTS:
      Of 407 patients enrolled, 132 (32%) underwent bronchoscopy. Of 132 BAL fungal
      cultures, 15 (11%) grew Cryptococcus neoformans. None of the patients were
      suspected to have pulmonary cryptococcosis on admission. The median CD4 count
      among those with pulmonary cryptococcosis was 23 cells per microliter
      (interquartile range = 7-51). Of 13 patients who completed 6-month follow-up, 4
      died and 9 were improved, including 5 who had started antiretroviral therapy but
      had not received antifungal medication. CONCLUSIONS: Pulmonary cryptococcosis is
      common in HIV-infected tuberculosis suspects in Uganda. Early initiation of
      antiretroviral therapy in those with isolated pulmonary infection may improve
      outcomes, even without antifungal therapy. This finding suggests that some HIV
      infected patients with C. neoformans isolated from respiratory samples may have
      colonization or localized infection.

PMID- 20150819
TI  - Physical and psychological symptoms and risk of virologic rebound among patients
      with virologic suppression on antiretroviral therapy.
AB  - OBJECTIVE: We examined the association of self-reported physical and
      psychological symptoms with subsequent virologic rebound among patients with
      viral suppression on combination antiretroviral therapy (cART). METHODS: We
      included 188 HIV patients from a routine London clinic, who completed a
      questionnaire on heath/treatment issues in 2005, and were on cART, with viral
      load (VL) < 50 c/mL. Symptom measures were based on the Memorial Symptom
      Assessment Scale Short Form, and additional questions: (1) physical symptom
      score; (2) psychological symptom score; (3) global symptom score; (4) total
      number of symptoms; (5) anxiety/depression; and (6) suicidal thoughts.
      Associations with time to (1) VL > 200 c/mL and (2) VL > 50 c/mL were assessed,
      considering each symptom measure separately. RESULTS: Of 188 patients, 22
      experienced VL > 200 c/mL and 46 experienced VL > 50 c/mL (median follow-up: 2.2
      years). Risk of VL > 200 c/mL was increased 4- to 5-fold for the highest versus
      lowest tertiles for the symptom scores (measures 1-3) and total number of
      symptoms (measure 4), and almost 4-fold for anxiety/depression (measure 5).
      Associations remained after adjustment for demographic and treatment-related
      factors (P = 0.006 to P = 0.050, measures 1-5), and were little attenuated after
      additional adjustment for subject-reported nonadherence (P = 0.011 to P = 0.072).
      There was a weaker, nonsignificant association with suicidal thoughts (measure
      6). For risk of VL > 50 c/mL, all symptom measures were positively associated
      with rebound risk (P = 0.019 to P = 0.053, measures 1-6, adjusted for demographic
      and treatment-related factors; P = 0.022 to P = 0.084 after additional adjustment
      for nonadherence). CONCLUSIONS: Among patients on successful cART, physical and
      psychological symptoms were strongly predictive of viral rebound. Simple symptom
      inquiry may be valuable in the clinical setting to identify patients at risk of
      treatment failure, and provide opportunity for intervention.

PMID- 20150820
TI  - Aortic root surgery in Marfan syndrome: Bentall procedure with the composite
      mechanical valved conduit versus aortic valve reimplantation with Valsalva graft.
AB  - OBJECTIVES: The aim of the study is to compare mid-term results of Bentall aortic
      root replacement with composite mechanical valved conduit and aortic valve
      reimplantation procedure using the Valsalva graft for the treatment of aortic
      root aneurysm in patients with Marfan syndrome. METHODS: We retrospectively
      compared data of 23 patients (mean age 38 + or - 14 years) who had undergone the
      Bentall procedure (group B) to those of 24 patients (mean age 36 + or - 12 years)
      who had undergone aortic valve reimplantation (group R) during a 14-year period.
      Follow-up (mean duration 65 + or - 44 months) was 100% complete. RESULTS: There
      were no operative deaths in either group. In group B, as compared with group R,
      preoperative aortic insufficiency (3.2 + or - 1.1/4 vs. 1.7 + or - 1.4/4, P <
      0.001), ascending aorta diameter (55.8 + or - 4.9 vs. 44.1 + or - 8.7 mm, P =
      0.001) were prevailing; cardiopulmonary bypass (107 + or - 51 vs. 145 + or - 32
      min, P < 0.05) and aortic cross-clamp (77 + or - 17 vs. 116 + or - 30 min, P =
      0.005) times were shorter. Eight-year survival and freedom from cardiac death and
      reoperation were 91 + or - 6, 96 + or - 4 and 100% in group B and 100, 100 and 91
      + or - 6% in group R, respectively (P = NS for all comparisons). At follow-up,
      echocardiography showed significant improvement of left ventricular ejection
      fraction (0.60 + or - 0.10 vs. 0.52 + or - 0.09 preoperatively, P = 0.01) and end
      systolic diameter (34 + or - 5 vs. 47 + or - 14 mm, P = 0.001) in group B and
      significant reduction of preoperative aortic insufficiency (0.7 + or - 1.0/4 vs.
      1.7 + or - 1.4/4, P = 0.01) and aortic annulus (24 + or - 2.4 vs. 33 + or - 5 mm,
      P = 0.01) in group R. CONCLUSION: In Marfan patients, the Bentall procedure is
      associated with excellent mid-term outcome. The reimplantation technique, adopted
      for less dilated aortas, provides similarly satisfactory results. The Valsalva
      graft seems, with time, to allow a stable aortic valve function.

PMID- 20150821
TI  - Sirolimus versus paclitaxel-eluting stents in small coronary vessels: long-term
      outcomes from a single-center registry.
AB  - OBJECTIVE: Several studies showed that small vessel diameter is a determinant of
      increased risk of adverse events after stenting. The efficacy of different drug
      eluting stent types implanted in small vessels has still not been established.
      The aim of the present observational study was to compare long-term clinical
      outcomes after sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES)
      implantation in lesions located in small coronary vessels. METHODS: For the
      purpose of this analysis patients undergoing SES or PES implantation in vessels
      with diameter 2.5 mm or less, from May 2002 to December 2006, were included. Long
      term rates of major adverse cardiac events were evaluated and compared between
      the two groups. Independent predictors of major adverse cardiac events were also
      investigated. RESULTS: A total of 336 patients were included, 225 were treated
      only with SES and 111 only with PES. During a mean follow-up of 23.3 +/- 12.1
      months the major adverse cardiac events rates were 12.8 versus 13.6%, P = 0.98 in
      SES versus PES groups, respectively. The rates of target lesion revascularization
      (8.0 versus 6.3%, P = 0.75), mortality (3.5 versus 4.5%, P = 0.88) and myocardial
      infarction (2.6 versus 4.5%, P = 0.41) were similar between SES and PES,
      respectively. The overall thrombosis rate was also not significantly different in
      SES and PES groups (1.3% SES versus 4.5% PES, P = 0.12). CONCLUSION: In this
      study SES and PES provided similar long-term results after treatment of lesions
      in small vessels. Nevertheless, larger randomized studies are needed to confirm
      these findings.

PMID- 20150822
TI  - Spontanous periodic breathing is associated with sympathetic hyperreactivity and
      baroreceptor dysfunction in hypertension.
AB  - OBJECTIVES: Intermittent periods of hypoxemia such as during periodic breathing
      are associated with hypertension and increased sympathetic activity. In patients
      with sleep apnea syndrome, hypertension is common. Treating apnea improves
      hypertension and reduces sympathetic outflow. The aim of the present study was to
      investigate the phenomenon and mechanisms of spontaneous periodic breathing in
      patients with hypertension. METHOD: We examined 43 hypertensive patients with
      untreated hypertension without left-ventricular dysfunction, heart failure or
      sleep apnea syndrome. Muscle sympathetic nerve activity (MSA), heart rate (HR),
      blood pressure (BP) and respiration were continuously recorded at rest and during
      cold-pressor testing. Oxygen and a CO2-enriched gas were used to test central and
      peripheral chemoreceptors, respectively. Baroreceptor gain was measured using the
      alpha method. RESULTS: Seven out of 43 patients showed spontaneous periodic
      breathing while awake. No difference in MSA, HR and BP was seen between patients
      with and without periodic breathing at rest except the breathing pattern.
      However, the cold-pressor test caused a larger increase of MSA in patients with
      periodic breathing (203 +/- 62 vs. 62 +/- 8%, P < 0.0001 by ANOVA), as well as
      systolic (46 +/- 6 vs. 25 +/- 3 mmHg, P = 0.002) and diastolic BP (26 +/- 5 vs.
      12 +/- 1 mmHg, P = 0.004, ANOVA). Baroreceptor gain was markedly higher in
      patients with periodic breathing. Chemoreceptor sensitivity was comparable.
      CONCLUSION: Spontaneous periodic breathing is relatively common in patients with
      hypertension and is associated with greatly enhanced responses to cold-pressor
      testing. We suggest increased baroreceptor gain and sympathetic outflow as a
      cause for the oscillatory respiration pattern via barorespiratory coupling.

PMID- 20150823
TI  - A proposed algorithm for diagnosing hypertension using automated office blood
      pressure measurement.
AB  - OBJECTIVE: To validate an algorithm for the interpretation of automated office
      blood pressure (AOBP) measurement based upon data from untreated patients
      referred by physicians in the community for 24-h ambulatory blood pressure
      monitoring (ABPM). METHODS: An algorithm for interpreting AOBP readings was
      developed taking into account the previously documented equivalence of AOBP and
      mean awake ambulatory BP (ABP; mmHg), which were each classified as optimum BP
      (<130/80), borderline BP (130-139/80-89) and hypertension (>or=140/90). This
      classification was applied to data derived from 254 untreated patients undergoing
      24-h ABPM, AOBP and routine manual BP taken at the patient's own family
      physician's office. RESULTS: The mean awake ABP (135.3 +/- 12.4/81.0 +/- 10.2)
      was similar to the mean AOBP (132.6 +/- 17.4/80.0 +/- 11.1) with both values
      being significantly (P < 0.001) lower than the routine manual BP (149.7 +/-
      15.2/89.3 +/- 9.5). Of the 69 patients with a systolic AOBP at least 140, only
      five (7.3%) exhibited white-coat hypertension with a normal mean awake ambulatory
      systolic BP less than 130. Similarly, of the 47 patients with a diastolic AOBP at
      least 90, none had optimum BP (diastolic BP < 80 mmHg on ABPM). White-coat
      hypertension was significantly (P = 0.005/P = 0.006) more prevalent for
      systolic/diastolic BP (22.1%/13.4%) when routine, manual BP readings were
      analysed. CONCLUSION: In contrast to routine manual office BP, a diagnosis of
      hypertension by AOBP is unlikely to be associated with an optimum awake ABP.

PMID- 20150824
TI  - Nocturnal blood pressure and progression to end-stage renal disease or death in
      nondiabetic chronic kidney disease stages 3 and 4.
AB  - OBJECTIVE: The objective was to assess the role of office and ambulatory blood
      pressure (BP) on the development of end-stage renal disease (ESRD) in nondiabetic
      chronic renal failure. DESIGN AND METHOD: Seventy-nine patients [mean age 57
      (standard deviation 11) years, 47 men, BMI 28 (4), office BP 151 (25)/92 (14)
      mmHg, estimated glomerular filtration rate 28 (14) ml/min per 1.73 m3] were
      included. The causes of renal disease were nephrosclerosis (n = 33),
      glomerulonephritis (n = 19), interstitial (n = 12) and others (n = 15). The
      average follow-up was 44 months (range 9-72 months). The primary outcome was a
      composite of death, from any cause, or the development of ESRD that require
      initiation of renal replacement therapy. In all patients, 24-h ambulatory BP
      monitoring and left ventricular mass assessment were performed at the beginning
      of the study. RESULTS: During the follow-up period, 41 (52%) patients progressed
      to ESRD. In addition, nine (11%) patients died, four before reaching ESRD. Then
      the combined endpoint rate, 45 patients, was 6.3/100 patients per year. In a
      multivariate Cox proportional hazard model, which includes age, sex, angiotensin
      converting enzyme inhibitor/angiotensin II receptor blocker status and the
      estimated glomerular filtration rate, office BP still provided no further
      prognostic information on risk of the primary outcome. In addition, daytime
      ambulatory BP and the no-dipper status did not further discriminate in terms of
      predicting endpoint. Nocturnal SBP more than 130 mmHg was associated with a
      doubling of risk [heart rate 2.07 (95% confidence interval 1.01-4.25)] on top of
      the other significant factors. CONCLUSION: Glomerular filtration rate and
      nocturnal SBP values, but not nondipper pattern, were associated with risk to
      develop ESRD.

PMID- 20150825
TI  - Efficacy and safety of cisplatin/pemetrexed versus cisplatin/gemcitabine as first
      line treatment in East Asian patients with advanced non-small cell lung cancer:
      results of an exploratory subgroup analysis of a phase III trial.
AB  - INTRODUCTION: We conducted an exploratory, post hoc, subgroup analysis of the
      East Asian (EA) patients in a multinational phase III trial to determine whether
      the efficacy results for this subgroup were consistent with those observed for
      the entire study population. METHODS: Thousand seven hundred twenty-five patients
      with advanced non-small cell lung cancer (NSCLC), including 126 EA patients
      (7.3%) from Taiwan and Korea, were enrolled in the trial and randomly assigned
      first-line chemotherapy with cisplatin and pemetrexed (CP; n = 862) or cisplatin
      and gemcitabine (CG; n = 863). Adjusted Cox proportional hazards models were used
      to compare overall survival and progression-free survival between the treatment
      arms in the EA subgroup. Median time-to-event data were estimated with the Kaplan
      Meier method. RESULTS: Consistent with the results for the entire study
      population, survival in the EA subgroup trended in favor of CP over CG in
      patients with non-squamous histology, despite the more frequent use of post
      discontinuation targeted therapy in the CG arm. The opposite trend was noted for
      patients with squamous tumors. A higher proportion of patients in the EA subgroup
      were never smokers compared with the entire study population. A trend toward
      improved survival with CP compared with CG was seen regardless of smoking status,
      particularly in non-squamous patients. CONCLUSIONS: The key finding of this
      subgroup analysis was that the NSCLC histology effect on treatment outcomes for
      pemetrexed-treated patients seen in the entire study population was also apparent
      in the EA subgroup. The potential prognostic influence of race, histology
      subtype, and smoking status should be assessed in future NSCLC studies.

PMID- 20150826
TI  - Comprehensive molecular analyses of lung adenocarcinoma with regard to the
      epidermal growth factor receptor, K-ras, MET, and hepatocyte growth factor
      status.
AB  - BACKGROUND: The mutation and amplification of oncogenic genes are associated with
      carcinogenesis and tumor growth. The purpose of this study was to clarify the
      role of the epidermal growth factor receptor (EGFR), K-ras, MET, and hepatocyte
      growth factor (HGF) status in lung adenocarcinoma. METHODS: Tumor specimens were
      collected from 183 patients who underwent a complete resection for adenocarcinoma
      of the lung from 2003 to 2007 in our department. The genetic status of the EGFR
      and K-ras genes were investigated by polymerase chain reaction (PCR)-based
      analyses. Immunohistochemistry and real time PCR assays were used to evaluate the
      MET gene regarding to tyrosine phosphorylation and amplification, respectively.
      HGF status was evaluated by immunohistochemistry. RESULTS: The mutations of EGFR
      and K-ras were detected in 64 (35%) and 17 patients (9%), respectively. The
      tyrosine 1234/1235 phosphorylation of MET (p-MET 1234/1235) and MET amplification
      was identified in 12 (7%) and 8 (4%) specimens, respectively. Positive expression
      of HGF was identified in 104 specimens (57%). An EGFR mutation was found
      significantly more frequently in females and in tumors with wild type of K-ras
      and without MET amplification. A p-MET 1234/1235 was found significantly more
      frequently in the tumors with a positive expression of HGF. A multivariate
      survival analysis demonstrated that the wild type of K-ras, negative p-MET
      1234/1235, and positive HGF expression were independently associated with an
      increased risk of poor survival. CONCLUSIONS: The occurrence of MET amplification
      and EGFR/ K-ras mutations might be mutually exclusive suggesting several distinct
      mechanisms in the development of lung adenocarcinoma. The wild type of K-ras,
      negative p-MET 1234/1235, and positive expression of HGF may be a useful marker
      for predicting poor prognosis of patients who underwent surgical resection of
      lung adenocarcinoma.

PMID- 20150827
TI  - A multi-institution phase I/II trial of triweekly regimen with S-1 plus cisplatin
      in patients with advanced non-small cell lung cancer.
AB  - INTRODUCTION: To determine the dose-limiting toxicity and recommended dose (RD)
      of cisplatin (CDDP) combined with S-1 (tegafur, 5-chloro-2, 4-dihydroxypyridine,
      and potassium oxonate) for patients with non-small cell lung cancer and to
      evaluate efficacy and toxicity of this regimen at RD. METHODS: Patients with
      stages III and IV non-small cell lung cancer received 3-week cycles of treatment,
      each consisting of oral administration of S-1 at 80 mg/m in 2 divided doses per
      day for 14 consecutive days, intravenous administration of CDDP (60 mg/m, 70
      mg/m, or 80 mg/m) on the first day, and no medication during the subsequent 7
      days. The primary objective of phase I study was to estimate the maximum
      tolerable dose and the RD, and the primary end point of phase II study was
      response. RESULTS: RD of CDDP in the analysis of 18 eligible patients was 60
      mg/m. Evaluation of efficacy and toxicity at RD in 55 eligible patients showed
      that partial response was observed in 18 patients (32.7%, 95% confidence
      interval: 20.7-46.7%). The median survival time was 18.1 months, and the time to
      disease progression was 3.8 months. Grade 3 or severer adverse events were
      observed in 27 patients (49.1%). CONCLUSIONS: CDDP combined with S-1 showed a
      satisfactory overall survival time and acceptable toxicity profile. However, the
      response as the primary end point did not reach the predetermined threshold
      level.

PMID- 20150828
TI  - KCNH2 pharmacogenomics summary.

PMID- 20150830
TI  - Delirium after spinal surgery in Korean population.
AB  - STUDY DESIGN: The incidence and risk factors of postoperative delirium were
      retrospectively examined in patients who had spine surgery for degenerative
      lumbar disease. OBJECTIVE: The aim of this study is to examine the incidence, pre
      and postoperative risk factors and clinical results of postoperative delirium
      after spine surgery. SUMMARY OF BACKGROUND DATA: Postoperative delirium is of
      great concern in older patients. Patients with postoperative delirium tend to
      have delay in functional restoration and difficulty in postoperative care. But to
      author's knowledge this is the first report to postoperative delirium after spine
      surgery in South Korean population. METHODS: Eighty-one patients over 70 years of
      age, who underwent spinal fusion for degenerative lumbar disease from November
      2000 and March 2007 were selected. We analyzed the relation between postoperative
      delirium and such variables as operation time, intraoperative blood loss and
      transfusion, fusion level, comorbidity and laboratory data checked before surgery
      and at 1 day after surgery. RESULTS: Postoperative delirium was found in 11
      patients (13.6%). There were significant relationships between postoperative
      delirium and comorbidity such as cerebral vascular disease and gastric ulcer.
      Hemoglobin and hematocrit levels at 1 day after surgery and albumin level before
      surgery was significantly lower than in control group. Oswestry disability index
      was improved from 50.4% to 27.6% in delirium group and from 48.5% to 24.9% in
      control group. Hospitalization period was significantly longer in delirium group.
      CONCLUSION: History of cerebral vascular disease, low hemoglobin and hematocrit
      levels at 1 day after surgery, and bad nutritional status were risk factors for
      delirium. As it is of great concern in older patients, careful observation is
      necessary for the management of patients with risk factors for delirium.

PMID- 20150829
TI  - Cytochrome P450 2C9-CYP2C9.

PMID- 20150831
TI  - The presentation, incidence, etiology, and treatment of surgical site infections
      after spinal surgery.
AB  - STUDY DESIGN: Descriptive, retrospective cohort analysis. OBJECTIVE: To evaluate
      the presentation, etiology, and treatment of surgical site infections (SSI) after
      spinal surgery. SUMMARY OF BACKGROUND DATA: SSI after spine surgery is frequently
      seen. Small case control studies have been published reporting the results of
      treatment options of SSI. We performed this study to identify the most common
      clinical and laboratory presentation of a SSI, the most frequently seen infective
      organism, and evaluate the effectiveness of current treatment. METHODS: All
      patients who underwent spinal surgery at our institution for diagnosis other than
      infection between June 1996 and December 2005 (N=3174) were reviewed. All cases
      of SSI were identified. Patient and operative characteristics were reviewed.
      Infection type (deep or superficial), treatment course, laboratory and culture
      results were abstracted. RESULTS: A total of 132 cases of SSI (84 deep and 48
      superficial) were identified. About 72.7% of the SSI were detected as outpatients
      an average 28.7 days (deep, 29.9; superficial, 25.2) after the index procedure.
      Wound drainage was the most common complaint (68.2%). C-reactive protein level
      was elevated in 98.0%, erythrocyte sedimentation rate was elevated in 94.4%, but
      only 48.6% had elevated white blood cell count. Staphylococcus aureus was
      isolated in 72.6% of deep and 85.7% of superficial positive cultures. Seventy-six
      percent of deep SSI could be treated with a single debridement to clear the SSI.
      Instrumentation was retained or primarily exchanged if loose in all cases. Around
      72.9% of superficial SSI were treated without formal debridement in the operating
      room. Antibiotic treatment was longer in deep SSI (40.8 vs. 19.6 days).
      CONCLUSION: Deep SSI following spinal surgery was effectively treated with single
      stage debridement and intravenous antibiotics. Superficial SSI could be treated
      effectively with local wound care and oral antibiotic therapy.

PMID- 20150832
TI  - Risk factors for lumbosacral plexus palsy related to pelvic fracture.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: We assessed risk factors for
      lumbosacral plexus palsy related to pelvic fracture that can be evaluated during
      the acute injury phase with diagnostics such as computed tomography (CT). SUMMARY
      OF BACKGROUND DATA: Many patients with pelvic fracture are in vital shock, with
      polytrauma and loss of consciousness, making an accurate neurologic examination
      very difficult in the emergency room. METHODS: This study included 22 patients
      who had AO classification type B or C pelvic fractures. The 22 patients had 27
      posterior osteoligamentary lesions. The average injury severity score (ISS) was
      27.5 (range, 16-50). Age, sex, ISS, suicidal jump, longitudinal displacement,
      sacral transverse fracture, pubic fracture, lumbar transverse process fracture,
      type of pelvic fracture (AO), and type of sacral fracture (Denis) were examined
      for a correlation with the lumbosacral plexus palsy. Using coronal reconstruction
      CT, we considered a 10 mm or greater displacement at the sacrum or sacroiliac
      joint to be a longitudinal displacement. Transverse sacral fracture was diagnosed
      by sagittal reconstruction CT. RESULTS: Of the 22 patients, 5 (22.7%) had
      lumbosacral plexus palsy (8 of 27 pelvic fractures) detected during treatment.
      The incidence of lumbosacral plexus palsy was not related to age, sex, ISS.
      Incidence of palsy was significantly higher when the patient's affected side had
      longitudinal displacement. Patients who had made a suicidal jump or had a sacral
      transverse fracture also had a significantly higher risk for lumbosacral plexus
      palsy. Palsy was not related to the type of pelvic fracture (AO) or sacral
      fracture (Denis). CONCLUSION: In this study, longitudinal displacement of the
      pelvis, transverse sacral fracture, and trauma from a suicidal jump were risk
      factors for lumbosacral plexus palsy. These risk factors were helpful in our
      examination of patients who had severe pelvic fracture with loss of
      consciousness.

PMID- 20150833
TI  - Combined anterior C2-C3 fusion and C2 pedicle screw fixation for the treatment of
      unstable hangman's fracture: a contrast to anterior approach only.
AB  - STUDY DESIGN: A retrospective clinical study was used to evaluate the effect of a
      new surgical treatment of the hangman's fractures. OBJECTIVE: To determine the
      treatment efficacy of combined anterior C2-C3 reduction and fusion and posterior
      compressive C2 pedicle screw fixation for the management of unstable hangman's
      fractures. SUMMARY OF BACKGROUND DATA: The classification of hangman's fractures
      as proposed by Levine-Edwards was used to classify and guide the treatment of
      these injuries. Most of these fractures respond to a variety of conservative
      therapies, but recently, earlier surgery has been increasingly advocated by
      authors from several countries for the rapid stabilization of these fractures. If
      surgery is indicated, an anterior approach using a C2-C3 reduction and fusion is
      preferred usually. Another well-accepted surgical method is the direct
      transpedicular osteosynthesis by the dorsal approach. However, there was rare
      report of the combined use of these 2 techniques. METHODS: A group of 45 surgical
      patients were all diagnosed with radiograph, magnetic resonance imaging (MRI),
      and 3D CT scans. Initial and final radiographs were measured for anterior
      translation and angulation of the C2-C3 complex. Initial external skull traction
      with extension was used in all patients after admission to reduce the fracture.
      Then an anterior C2-C3 discectomy followed by an interbody fusion and locking
      plate fixation was performed. Intraoperative reduction was confirmed by
      fluoroscopic control. About 29 patients therefore received anterior surgeries
      only since satisfactory reduction was achieved during the procedure. For the 16
      patients who had persistent large residual gaps after the anterior procedure,
      additional same stage posterior C2 compressive pedicle screws were placed.
      Clinical and radiologic comparisons were performed in these 2 groups. RESULTS:
      The follow-up ranged from 24 to 54 months, with an average 33.6 months. There was
      radiographic evidence of continuity of the fracture and the bone graft seen at
      4.7 months on average. Neck pain and neurologic deficits resolved in nearly all
      patients after surgery. The anterior translation of anterior-posterior surgery
      group decreased more significant compared to anterior surgery group, although
      with no statistical significance. The fractures were closed with a slight gap no
      more than 2 mm in anterior-posterior surgery group. The residual kyphosis in
      anterior-posterior surgery group was still a little larger than it in anterior
      surgery group. No internal fixation failures or infections were observed.
      CONCLUSION: We believe that the need for single stage 360 degrees  fusion of
      hangman's fractures can be somewhat predicted by a combination of high resolution
      imaging. For hangman's fractures with significant deformity and gapping, it is
      our experience that immediate single-stage anterior-posterior reduction,
      instrumentation, and arthrodesis achieve superior postoperative reduction and
      long-term functional outcomes.

PMID- 20150834
TI  - The influence of the insertion technique on the pullout force of pedicle screws:
      an experimental study.
AB  - STUDY DESIGN: The pullout strength of a typical pedicle screw was evaluated
      experimentally for different screw insertion techniques. OBJECTIVE.: To conclude
      whether the self-tapping insertion technique is indeed the optimum one for self
      tapping screws, with respect to the pullout strength. SUMMARY OF BACKGROUND DATA:
      It is reported in the literature that the size of the pilot-hole significantly
      influences the pullout strength of a self-tapping screw. In addition it is
      accepted that an optimum value of the diameter of the pilot-hole exists. For non
      self-tapping screw insertion it is reported that undertapping of the pilot-hole
      can increase its pullout strength. Finally it is known that in some cases
      orthopedic surgeons open the threaded holes, using another screw instead of a
      tap. METHODS: A typical commercial self-tapping pedicle screw was inserted into
      blocks of Solid Rigid Polyurethane Foam (simulating osteoporotic cancellous
      bone), following different insertion techniques. The pullout force was measured
      according to the ASTM-F543-02 standard. The screw was inserted into previously
      prepared holes of different sizes, either threaded or cylindrical, to conclude
      whether an optimum size of the pilot-hole exists and whether tapping can increase
      the pullout strength. The case where the tapping is performed using another screw
      was also studied. RESULTS: For screw insertion with tapping, decreasing the outer
      radius of the threaded hole from 1.00 to 0.87 of the screw's outer radius
      increased the pullout force 9%. For insertion without tapping, decreasing the
      pilot-hole's diameter from 0.87 to 0.47 of the screw's outer diameter increased
      its pullout force 75%. Finally, tapping using another screw instead of a tap,
      gave results similar to those of conventional tapping. CONCLUSION: Undertapping
      of a pilot-hole either using a tap or another screw can increase the pullout
      strength of self-tapping pedicle screws.

PMID- 20150835
TI  - Cervical myelopathy: a clinical and radiographic evaluation and correlation to
      cervical spondylotic myelopathy.
AB  - STUDY DESIGN: Retrospective analysis of a cohort of patients treated between
      April 2006 and January 2008, and diagnosed with cervical degenerative disease.
      OBJECTIVE: To determine the correlation of the clinical findings associated with
      cervical myelopathy to the presence of spinal cord compression or cord signal
      abnormalities on magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA:
      There are numerous reports describing the radiographic features of cervical
      spondylosis, however, no publication specifically describes the association
      between the physical signs of cervical myelopathy and the presenting imaging
      findings. METHODS: Myelopathy was defined as the presence of greater than one
      long-tract sign localized to the cervical spinal cord (Hoffman or Babinski signs,
      clonus, hyper-reflexia, crossed abductor sign, and/or gait dysfunction) on
      physical examination in the absence of other neurologic condition(s). The
      presence of these signs, MRI imaging features of spinal cord compression and
      hyperintense T2 intraparenchymal cord signal abnormality, and patient
      demographics were recorded. RESULTS: One hundred three patients met inclusion
      criteria (age >18, symptomatic cervical degenerative disease and complete
      neurologic assessment). Of these, 54 had clinical findings of cervical
      myelopathy. Radiographic features of cord compression were present in 62% of
      patients, and 84% had myelopathy on examination. No patients without cord
      compression presented with myelopathy (P < 0.0001). Thirty-five percent of the
      patients presented with hyperintense signal on T2 MRI within the spinal cord
      parenchyma. This finding correlated with the presence of myelopathy (P < 0.0001).
      Multivariate analysis on the subset with cord compression indicates that the
      likelihood of myelopathy increased with the presence of cord signal
      hyperintensity (odds ratio [OR], 11.4), sensory loss (OR, 16.9), and age (OR,
      1.10 per year). CONCLUSION: The diagnosis of cervical myelopathy is based on
      presenting symptoms and physical examination. This analysis illustrates that
      radiographic cervical spinal cord compression and hyperintense T2 intraparen
      chymal signal abnormalities correlate with the presence of myelopathic findings
      on physical examination.

PMID- 20150836
TI  - Reconstitution of experimental neurogenic bladder dysfunction using skeletal
      muscle-derived multipotent stem cells.
AB  - BACKGROUND.: Postoperative neurogenic bladder dysfunction is a major complication
      of radical hysterectomy for cervical cancer and is mainly caused by unavoidable
      damage to the bladder branch of the pelvic plexus (BBPP) associated with
      colateral blood vessels. Thus, we attempted to reconstitute disrupted BBPP and
      blood vessels using skeletal muscle-derived multipotent stem cells that show
      synchronized reconstitution capacity of vascular, muscular, and peripheral
      nervous systems. METHODS.: Under pentobarbital anesthesia, intravesical pressure
      by electrical stimulation of BBPP was measured as bladder function. The distal
      portion of BBPP with blood vessels was then cut unilaterally (experimental
      neurogenic bladder model). Measurements were performed before, immediately after,
      and at 4 weeks after transplantation as functional recovery. Stem cells were
      obtained from the right soleus and gastrocnemius muscles after enzymatic
      digestion and cell sorting as CD34/45 (Sk-34) and CD34/45 (Sk-DN). Suspended
      cells were autografted around the damaged region, whereas medium alone and CD45
      cells were transplanted as control groups. To determine the morphological
      contribution of the transplanted cells, stem cells obtained from green
      fluorescent protein transgenic mouse muscles were transplanted into a nude rat
      model and were examined by immunohistochemistry and immunoelectron microscopy.
      RESULTS.: At 4 weeks after surgery, the transplantation group showed
      significantly higher functional recovery ( approximately 80%) than the two
      controls ( approximately 28% and 24%). The transplanted cells showed an
      incorporation into the damaged peripheral nerves and blood vessels after
      differentiation into Schwann cells, perineurial cells, vascular smooth muscle
      cells, pericytes, and fibroblasts around the bladder. CONCLUSION.:
      Transplantation of multipotent Sk-34 and Sk-DN cells is potentially useful for
      the reconstitution of damaged BBPP.

PMID- 20150837
TI  - 2009 update of the ACC/AHA guidelines for the management of patients with ST
      elevation myocardial infarction and guidelines on percutaneous coronary
      intervention: what should we change in clinical practice?

PMID- 20150838
TI  - The role of the phosphodiesterase-4 inhibitor, roflumilast, in chronic
      obstructive pulmonary disease.

PMID- 20150839
TI  - The influence of simvastatin on selected inflammatory markers in patients with
      chronic obstructive pulmonary disease.
AB  - INTRODUCTION: There is growing evidence that chronic obstructive pulmonary
      disease (COPD) is a risk factor for coronary heart disease. Simvastatin is a
      hypolipemic drug with proven efficacy in the prevention of cardiovascular
      diseases. Observational studies showed that statins may be useful in the
      reduction of mortality from COPD. Experimental studies on animals showed anti
      inflammatory effects of statins on the lung tissue. OBJECTIVES: The aim of this
      study was to evaluate the influence of simvastatin on inflammatory markers in
      patients with COPD. PATIENTS AND METHODS: Fifty-six patients (aged 44-80 years)
      with stable COPD (a mean forced expiratory volume in 1 second [FEV1] 55%), were
      randomly assigned (1:1) to receive simvastatin 40 mg/day or to receive no statin
      treatment. Blood samples were collected before, 2 weeks, and 3 months after
      statin administration. The levels of fibrinogen, C-reactive protein (CRP), tumor
      necrosis factor-alpha, interleukin 6 (IL-6), and matrix metalloproteinase-9 were
      measured. RESULTS: The groups did not differ significantly in terms of
      demographic data, clinical symptoms, pharmacological treatment, spirometry, and
      lipid profile at baseline. Among comorbidities only arterial hypertension was
      more frequent in the statin group (32.1% vs. 17.9%, P = 0.03). After 2 weeks as
      well as 3 months of simvastatin treatment, no significant reduction of any
      measured inflammatory markers was observed. There was a nonsignificant reduction
      of CRP and IL-6 in the subgroup with FEV1 >50% during simvastatin treatment.
      There was a decrease in total cholesterol (from 5.7 to 4.7 mmol/l, P = 0.0018)
      and low-density lipoprotein cholesterol (from 3.46 to 2.47 mmol/l, P = 0.000037)
      in the statin group. CONCLUSIONS: In COPD patients, a 3-month treatment with
      simvastatin does not reduce circulating inflammatory markers.

PMID- 20150840
TI  - Elevated levels of 8-iso-prostaglandin F2alpha in acute coronary syndromes are
      associated with systemic and local platelet activation.
AB  - INTRODUCTION: Oxidative stress is an important causative factor in
      atherosclerosis. Isoprostanes are derivatives of arachidonate oxidized by
      reactive oxygen species (ROS). Oxidized lipids are markers of oxidative stress,
      important mediators of atherosclerosis, and activators of platelets. 8-iso
      prostaglandin F2alpha (8-iso-PGF2alpha) is a stable isoprostane and reliable
      marker of oxidative stress in vivo. OBJECTIVES: The aim of the study was to
      determine the level of oxidative stress in acute coronary syndromes (ACS) and its
      correlations with the para meters of hemo stasis. PATIENTS AND METHODS: Fourty
      nine patients aged 46 to 76 years, including 28 with ACS and 25 with stable
      coronary artery disease (CAD), were enrolled to the study. The levels of 8-iso
      PGF2alpha, soluble CD40 ligand (sCD40L), P-selectin (P-sel), beta
      thromboglobulin, and the thrombin-antithrombin complex (TAT) in the plasma of
      venous blood were determined. A microvascular injury model was also used to
      evaluate TAT generation and sCD40L levels in blood collected every 60 seconds at
      the site of standardized microvascular injury. RESULTS: 8-iso-PGF2alpha levels
      were significantly higher in ACS compared to CAD patients (363.2 +/-45.94 vs.
      328.2 -/+31.96 pg/ml, P = 0.011) and correlated with venous plasma levels of P
      sel and beta-thromboglobulin in the ACS (r = 0.66; P = 0.0005 and r = 0.62; P =
      0.001, respectively) and CAD groups (r = 0.46; P = 0.02 and r = 0.49; P = 0.01,
      respectively). In the microvascular injury model, the maximum concentrations of
      sCD40L in the ACS group were associated with plasma 8-iso-PGF2alpha levels (r =
      0.50, P = 0.01). No correlations between 8-iso-PGF2alpha and markers of thrombin
      generation in venous blood and microvascular injury model were observed.
      CONCLUSIONS: Plasma levels of 8-iso-PGF2alpha are significantly higher in ACS
      compared with stable CAD and correlate with platelet activation.

PMID- 20150841
TI  - Anti-livin antibodies: novel markers of malignant gastrointestinal cancers.
AB  - INTRODUCTION: Livin represents apoptosis inhibitors and may be important in
      cancer. OBJECTIVES: The aim of the study was to develop an anti-livin auto
      antibody assay and investigate its usefulness in the clinical practice in
      relation to gastrointestinal cancers (GIC). PATIENTS AND METHODS: We studied sera
      obtained from 36 patients with GIC and 59 healthy controls. A solid-phase
      radioimmunoassay to detect anti-livin antibodies in serum was developed.
      Polipropylene tubes were coated with recombinant human livin, and 100-fold
      dilutions of sera were incubated in these tubes. On the next day, the tubes were
      decanted, washed and labeled 125-I protein A was added. After 2-hour incubation,
      the tubes were washed and radioactivity was measured using the gamma counter.
      RESULTS: We observed a statistically significant difference between the presence
      and levels of anti-livin antibodies in sera of patients with GIC and in control
      subjects. Anti-livin auto antibodies were detected in 9 patients with GIC. Of
      note, the level of anti-livin antibodies was significantly elevated in 25% of GIC
      patients. The presence of anti-livin antibodies was confirmed with sodium dodecyl
      sulfate polyacrylamide gel electrophoresis and Western blotting. CONCLUSIONS: A
      high prevalence of anti-livin antibodies in patients with GIC indicates that they
      may be useful in the diagnosis of these malignancies.

PMID- 20150842
TI  - Reappraisal of the European guidelines on hypertension management: the European
      Society of Hypertension Task Force document: a short review.
AB  - The European Society of Hypertension Task Force document on reappraisal of the
      2007 European guidelines on hypertension addresses a number of studies published
      in the last 2 years to estimate their contribution to the expanding knowledge on
      hypertension. The importance of total cardiovascular risk with inclusion of
      subclinical cardiac, vascular, and renal organ damage was reemphasized, followed
      by a critical reappraisal of recommendations for the initiation of
      antihypertensive drug treatment in patients with high normal blood pressure (BP)
      and grade 1 hypertension. Whereas there is sufficient evidence for reducing BP
      below 140/90 mmHg in most hypertensives, the recommendation of previous
      guidelines to aim at a lower BP in diabetics and in patients at very high
      cardiovascular risk is not consistently supported by trial evidence. Moreover,
      the J-curve phenomenon may occur in patients at high cardiovascular risk. With
      regard to the choice of antihypertensive drugs, the conclusions of the 2007
      guidelines that diuretics, angiotensin-converting enzyme inhibitors, calcium
      antagonists, angiotensin receptor antagonists, and beta-blockers are suitable for
      initiation and maintenance of antihypertensive treatment are reinforced.
      Furthermore, apart from starting with combination therapy in certain conditions,
      adding a drug from another class to the initially prescribed one is preferred to
      increasing the dose of the first one. Some of the drug combinations recommended
      in 2007 are now regarded as more recommendable. In addition to the benefits of
      antihypertensive treatment in the elderly, the HYVET (Hypertension in the Very
      Elderly Trial) has shown that antihypertensive treatment also has benefits in
      octogenarians. The document ends with a number of issues in urgent need to be
      approached by new trials.

PMID- 20150843
TI  - Hemoglobin A1c for the diagnosis of diabetes: practical considerations.
AB  - The International Expert Committee recommends that the diagnosis of diabetes be
      made if hemo globin A1c (HbA1c) level is greater, similar 6.5% and confirmed with
      a repeat HbA1c test. The committee recommends against "mixing different methods
      to diagnose diabetes" because "the tests are not completely concordant: using
      different tests could easily lead to confusion". Fasting plasma glucose, 2-hour
      postglucose-load plasma glucose, and oral glucose tolerance tests are recommended
      for the diagnosis of diabetes only if HbA1c testing is not possible due to
      unavailability of the assay, patient factors that preclude its inter pretation,
      and during pregnancy. HbA1c testing has the advantages of greater clinical
      convenience, preanalytic stability, and assay standardization, but when used as
      the sole diagnostic criterion for diabetes, it has the potential for systematic
      error. Factors that may not be clinically evident impact HbA1c test results and
      may systematically raise or lower the value relative to the true level of
      glycemia. For this reason, HbA1c should be used in combination with plasma
      glucose determinations for the diagnosis of diabetes. If an HbA1c test result is
      discordant with the clinical picture or equivocal, plasma glucose testing should
      be performed. A diagnostic cut-off point of HbA1c greater, similar 6.5% misses a
      substantial number of people with type 2 diabetes, including some with fasting
      hyperglycemia, and misses most people with impaired glucose tolerance. Combining
      the use of HbA1c and plasma glucose measurements for the diagnosis of diabetes
      offers the benefits of each test and reduces the risk of systematic bias inherent
      in HbA1c testing alone.

PMID- 20150844
TI  - Syncope: diagnosis and management according to the 2009 guidelines of the
      European Society of Cardiology.
AB  - The European Society of Cardiology has recently revised its guidelines on the
      diagnosis and management of syncope. This document is a synopsis of their
      recommendations.

PMID- 20150845
TI  - Psychological aspects of dialysis: does cognitive appraisal determine the overall
      outcome?
AB  - Psycho logical aspects of renal replacement therapy have been studied by numerous
      researchers. However, many of these studies are of poor quality, involve small
      study groups, or focus only on a narrowly defined hypothesis. Due to a lack of
      general conceptual framework, it is difficult to generalize and inter pret the
      data, especially in terms of the cause-and-effect relationship. Further research
      is required to assess how patients with end-stage renal disease cope with
      dialysis-related stress. Particular emphasis should be placed on the preparation
      of experimental studies and clinical trials with a longer follow-up.

PMID- 20150846
TI  - Insulin resistance as a novel therapeutic target in patients with chronic kidney
      disease treated with dialysis.
AB  - Clinical significance of insulin resistance in patients with chronic renal
      failure treated with dialysis has not been fully elucidated and requires further
      research. The available data indicate that long-term dialysis therapy promotes
      the development of insulin resistance. Furthermore, it has been proven that
      insulin resistance in this patient group is a strong independent predictor of
      mortality from cardiovascular causes. Insulin resistance as a potential
      modifiable cardiovascular risk factor should be considered as a novel therapeutic
      target in patients undergoing both hemo dialysis and peritoneal dialysis.

PMID- 20150847
TI  - The "open" ICU: not just a question of time.

PMID- 20150848
TI  - The forearm tourniquet Bier block. Logic and authority versus science and
      experience.

PMID- 20150849
TI  - Open intensive care units: a regional survey about the beliefs and attitudes of
      healthcare professionals.
AB  - AIM: We aimed at assessing the opinion and degree of acceptance of physicians and
      nurses in Intensive Care Units (ICUs) toward an open ICU as our regional ethical
      committee has advised that ICU visitation policies be reformed using such a new
      approach. METHODS: This was a descriptive, cross-sectional, multicenter survey
      using the Beliefs and Attitudes toward Visitation in ICU Questionnaire mailed to
      the ICUs in our region. RESULTS: A total of 28 ICUs were invited, and 25 agreed
      to participate in this survey; 377 nurses and 230 physicians were surveyed with
      overall response rates of 94.9%% and 84.7%%, respectively. Nurses considered an
      open visiting policy to be an infringement on patient privacy (P<0.01), a
      possible interference with interactions between caregivers (P<0.01) and an
      impediment to their duties (P<0.05). They also significantly differed from
      physicians in considering open visitations a cause of more adverse hemodynamic
      events (P<0.05) and higher physiological and psychological stress for patients
      (P<0.05). With regard to attitudes, nurses strongly disagreed more frequently
      with the following: allowing everyone to visit the patient, accepting an open
      visitation policy in their unit, giving control of the visitation policy to the
      patient (P<0.01) and adapting visitation to the culture/ethnicity of the patients
      (P<0.0001). CONCLUSIONS: This study points out that, in our region, physicians
      are more liberal and able than nurses to "customize" their wards to the specific
      psychosocial and emotional needs of patients and visitors.

PMID- 20150850
TI  - Transcatheter implantation of an aortic valve: anesthesiological management.
AB  - AIM: Transcatheter aortic valve implantation (TAVI) is an emergent alternative
      technique to surgery in high-risk patients with aortic stenosis. Here, we
      describe the anesthesiological management of patients undergoing TAVI at our
      institution over an 18-month period. METHODS: After a proper assessment of
      surgical risk and comorbidities, 69 patients underwent TAVI with the
      transfemoral/subclavian approach. Both Edwards-Sapien and Corevalve prostheses
      were implanted. The anesthetic regimen consisted of general anesthesia or local
      anesthesia plus sedation. RESULTS: Twenty-seven patients received general
      anesthesia, and 42 received local anesthesia plus sedation. Procedural
      complications included prosthesis embolization (2), ascending aorta dissection
      (1), ventricular fibrillation following rapid ventricular pacing (8), vascular
      access site complications (17), and the valve-in-valve procedure (1). Three
      patients had to be converted from local anesthesia to general anesthesia (one
      patient had refractory ventricular fibrillation, and two patients were restless).
      All patients were alive at the 30-day follow-up. Mechanical ventilation time was
      8.5+/-0.03 h. Mean ICU stay was 20.1+/-2.89 h. Postoperative complications
      included acute renal dysfunction (11), advanced atrioventricular block (9), and
      stroke (1). Thirty-six out of 42 (86%) patients were alive at the 6-month follow
      up. CONCLUSIONS: TAVI is feasible in high-risk patients who would not be able to
      undergo surgical valve replacement. Hemodynamic management is the main concern of
      intraoperative anesthesiological management. General or local anesthesia plus
      sedation are both valid alternative techniques that can be titrated according to
      patient characteristics. Close postoperative monitoring in the ICU is required.

PMID- 20150851
TI  - Forearm IVRA, using 0.5% lidocaine in a dose of 1.5 mg/kg with ketorolac 0.15
      mg/kg for hand and wrist surgeries.
AB  - AIM: Local anesthetic toxicity remains one of the most dreaded complications of
      the intravenous regional anesthesia (IVRA) technique. It results from the sudden
      release of a large amount of local anesthetic (LA) into the systemic circulation.
      This release can occur when the tourniquet deflates accidentally during the
      procedure or when it is deflated intentionally at the end of the procedure to
      terminate the anesthesia. The forearm tourniquet IVRA technique may offer
      distinct advantages over the conventional upper arm tourniquet IVRA technique.
      Use of a forearm tourniquet allows the dosage of local anesthetic to be decreased
      to almost half of what is required with an upper arm tourniquet, and the
      incidence of tourniquet pain has been reported to be less with forearm
      tourniquet. In this study, authors assessed the clinical efficacy of
      administering IVRA with lidocaine plus ketorolac using either a forearm or upper
      arm tourniquet. METHODS: Upper arm IVRA was established using 0.5% lidocaine at a
      dose of 3 mg/kg with ketorolac at 0.3 mg/kg. Forearm IVRA was established using
      0.5 % lidocaine at a dose of 1.5 mg/kg with ketorolac at 0.15 mg/kg. Quality of
      surgical anesthesia, onset, duration of sensory block and postoperative surgical
      pain and analgesic use were recorded and assessed. The incidence of local
      anesthetic toxicity and local complications due to the tourniquet were also
      recorded. RESULTS: Surgical anesthesia was assessed as excellent or good (grade
      0/1) in all 20/20 patients who received IVRA using an upper arm tourniquet and in
      19/20 patients who received IVRA using a forearm tourniquet (P=1.00). Onset as
      well as regression of sensory block was similar in both the groups. Post
      operative VAS scores at 30 min and 60 min were statistically comparable between
      the two groups, as was the analgesic use in the first 24 h. CONCLUSIONS: In
      conclusion, forearm IVRA provides effective perioperative anesthesia and
      analgesia. The technique results in a similar clinical profile as upper arm IVRA
      while using half the dose of both lidocaine and ketorolac.

PMID- 20150852
TI  - The pharmacodynamic effects of rocuronium during general anesthesia in patients
      with type 2 diabetes mellitus.
AB  - AIM: The aim of this prospective study was to investigate whether the
      neuromuscular response to rocuronium is affected by the presence of type 2
      diabetes mellitus. METHODS: Neuromuscular functions were measured after the
      administration of 0.6 mg/kg rocuronium with train-of-four stimulations in
      patients with type 2 diabetes mellitus (DM, N=14) and without diabetes mellitus
      (control, N=14) during isoflurane based general anesthesia. The onset time,
      clinical duration and recovery index of rocuronium were compared in the two
      groups. RESULTS: The mean onset time (136 +/- 40 vs 118 +/- 20 s), clinical
      duration (51 +/- 11 vs 48 +/- 11 min) and recovery index (6.0 +/- 2.5 vs 5.9 +/-
      1.4 min) of the neuromuscular block were not significantly different between the
      DM and control groups, respectively (p>0.05). CONCLUSIONS: The present study has
      proven that the rocuronium-induced neuromuscular block was not affected in
      patients with type 2 diabetes mellitus during isoflurane based general
      anesthesia.

PMID- 20150853
TI  - Urinary retention after total hip and knee arthroplasty.
AB  - Postoperative urinary retention (POUR) occurs after lower joint arthroplasty with
      an incidence between 0% and 75%. This vast range reflects the differences in
      diagnosis and management of POUR. At present, clinical practice includes either
      preoperative insertion of an indwelling catheter to be removed after 24-48
      postoperative hours or postoperative intermittent in-and-out catheterization
      performed either at scheduled times (every 6-8 hours) or as necessary. Although
      the most effective approach remains an issue of debate, there is a growing
      consensus that postoperative intermittent catheterization guided by ultrasound
      could decrease the incidence of complications related to POUR. The purpose of the
      present article is to review the published data on the effects of analgesia
      techniques on the development of POUR after hip and knee arthroplasty. General
      and regional anesthesia are implicated in the etiology of POUR; however, type and
      duration do not correlate with its incidence. Of the different postoperative
      analgesic techniques currently used, continuous peripheral nerve block has the
      least impact on POUR.

PMID- 20150854
TI  - Thrombelastography in the surgical patient.
AB  - Coagulopathy in surgical patients is an important factor in triggering major
      perioperative complications, i.e., intra- or postoperative bleeding and thrombo
      embolic events associated with an increased mortality and morbidity. Different
      methods exist to assess the coagulation status of patients before, during and
      after surgery. Routine coagulation tests have long been considered to be the
      clinical standard. However, these tests have considerable limitations.
      Information regarding the kinetics of clot formation, clot strength, interaction
      of the coagulation components, platelet function and fibrinolysis is not
      available. Moreover, there is an important delay in obtaining test results. In
      contrast, thrombelastography and thrombelastometry, which both measure the visco
      elastic properties of whole blood, allow the dynamic assessment of a developing
      clot, from fibrin formation to clot strengthening and clot lysis. Both techniques
      are increasingly being used in daily clinical practice in order to detect
      perioperative coagulopathy and to guide predominantly pro-coagulant therapy in
      different settings. This article provides an overview of both techniques,
      thrombelastography (TEG) and thrombelastometry (ROTEM), and their field of
      perioperative application considering of recently published data.

PMID- 20150855
TI  - Postoperative pulmonary complications.
AB  - Postoperative pulmonary complications (PPC) account for a substantial portion of
      the risks related to surgery and anesthesia and are a source of postoperative
      morbidity, mortality and longer hospital stays. The current basis for our
      understanding of the nature of PPC is weak; only a small number of high-quality
      studies are available, a uniform definition has not emerged, and studies have
      focused on specific patients and kinds of surgeries. Current evidence suggests
      that risk factors for PPC are related to the patient's health status and the
      particular anesthetic and surgical procedures chosen. Age, general co-morbidity,
      pre-existing respiratory and cardiac diseases, the use of general anesthesia and
      the overall surgical insult. are the most significant factors associated with
      complications. Election of anesthetic technique, postoperative analgesia and
      physical therapy seem to be the preventive measures that are best supported by
      evidence.

PMID- 20150856
TI  - Anesthetic management for right upper extremity amputation due to recidivous
      cutaneous carcinoma and acute postoperative pain control in patients affected by
      epidermolysis bullosa.
AB  - A 22-year-old male who was affected by epidermolysis bullosa (EB) and xeroderma
      pigmentosa (with structural and pathological changes that preclude orotracheal
      intubation) underwent right upper extremity amputation and ipsilateral axillary
      lymphadenectomy. The patient was operated without intubation, thereby assuring an
      optimal state of acute postoperative pain control by regional anesthesia.
      Intravenous administration of ketamine and remifentanil plus low-dose sevoflurane
      resulted in anesthesia with spontaneous breathing by the patient. Moreover, the
      intraoperative brachial plexus nerve block before amputation followed by
      positioning of an epidural catheter to deliver continuous infusion of local
      anesthetics close to the cut nerves during surgery obtained a very good level of
      acute postoperative pain control.

PMID- 20150857
TI  - Successful emergent reintubation using the Aintree intubation catheter and a
      laryngeal mask airway.
AB  - Tracheal extubation can be potentially catastrophic, especially in patients with
      difficult airways. This article describes a case where planned extubation in a
      patient with a large tongue lesion led to complete airway obstruction and
      subsequent cardiac arrest. Reintubation was facilitated using a laryngeal mask
      airway and an Aintree intubation catheter.

PMID- 20150858
TI  - The Hutchinson-Gilford Progeria Syndrome: a case report.
AB  - The HGPS (Hutchinson Gilford Progeria Syndrome) is a rare genetic disorder with
      an incidence of 1 per 8 million live births. Originally described in 1886, less
      than 100 cases have been reported. The syndrome is characterized by premature
      aging with changes in many organs. The diagnosis is usually made by age 2, the
      mean survival age is 13.4 years and the most common cause of death is myocardial
      infarction. Recent genetic advances have identified the cause as a defect in the
      LMNA gene of chromosome 1.

PMID- 20150859
TI  - Do we provide optimal care to patients with acute neurological injuries?

PMID- 20150860
TI  - Pulseless ventricular tachycardia: to shock or not to shock?

PMID- 20150861
TI  - A year in Review in Minerva Anestesiologica, 2009.

PMID- 20150862
TI  - Acute ischemia of right superior arm: an unusual presentation of Takotsubo
      cardiomiopathy?

PMID- 20150863
TI  - Research into the chronodisruption-cancer theory: the imperative for causal
      clarification and the danger of causal reductionism.
AB  - A cascade of investigations into the validity of the chronodisruption-cancer
      theory (CD-CT), proposed 2008 in Neuroendocrinology Letters as a synthesis of
      abundant experimental and tantalizing - but still limited - epidemiological data,
      can be expected in coming years. In view of the possible public health relevance
      of the suggested links between chronodisruption, defined as the disruption of the
      temporal organization or order of biological rhythmicity over days and seasons,
      and the development of disease, including cancer, we provide practical aspects
      which should be considered for the planning, conduct and the very interpretation
      of such studies. The interrelated considerations address two facets: first, the
      critical necessity of causal clarification can be evinced appropriately by
      Poole's earlier contribution to the Journal. Researchers into the validity of the
      CD-CT should certainly consider Poole's 2002 illustration via causal graphs for
      shift work, light at night and breast cancer of the subtleties that can arise in
      the use of exposure surrogates of different kinds. Second, we emphasize the
      importance of considering the Zeitgeber multiplicity to avoid causal reductionism
      in epidemiologic - but also other - chronodisruption research.

PMID- 20150864
TI  - Technetium-99m ethyl cysteinate dimer (ECD) cerebral accumulation and symptom and
      sign severity during hypothyroidism.
AB  - OBJECTIVE: The purpose of this study was to correlate hypothyroid-related
      symptomatology with regional cerebral blood flow (rCBF) during hypothyroidism.
      MATERIALS AND METHODS: Nine thyroidectomized patients underwent
      neuropsychological testing and single photon emission computed tomography (SPECT)
      of their brains with technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), a
      lipophilic cerebral blood flow radiotracer, while hypothyroid, and again
      following thyroid hormone replacement. Neuropsychological test scores and TSH
      levels while hypothyroid were correlated with rCBF in hypothyroid-affected areas
      of the brain. RESULTS: Correlations were found during hypothyroidism between the
      noted parameters and ECD radiotracer accumulation in the following respective
      regions, all of which demonstrated hypothyroid-related cerebral blood flow (CBF)
      aberrations: TSH and left middle occipital gyrus; psychomotor performance speed
      and left precentral gyrus; and depression and right middle frontal gyrus, left
      middle frontal gyrus, right insula, and left thalamus. CONCLUSIONS: Severity of
      psychomotor impairment and depression, and TSH level during hypothyroidism
      appeared to correlate with CBF to brain regions associated with motor activity,
      mood and vision, respectively; and previously shown to manifest significantly
      altered rCBF during hypothyroidism.

PMID- 20150865
TI  - Effects of certain antioxidants on lipid peroxidation process in lung homogenates
      of L thyroxine-receiving rats.
AB  - OBJECTIVE: A possible role of antioxidants in thyreotoxicosis was investigated.
      We examined the parameters of lipid peroxidation (LPO): conjugated dienes (CD),
      malondialdehyde (MDA), Schiff bases (SB) in lung homogenates of male Wistar rats.
      METHODS: Two control groups were created: Group 1 - intact animals and Group 2 -
      animals injected with 0,9% NaCl. In Experiment I, the animals received L-thyroxin
      (LT4) i.p. (Groups 3-7). After one week the rats received additionally: Group 4 -
      melatonin (MEL); Group 5 - propylthiouracil (PTU); Group 6 - Ambroxol (AMB);
      Group 7 - N-acetylocysteine (NAC). In Experiment II, the animals received only
      antioxidants. RESULTS: In Experiment I, we noticed a significantly higher MDA and
      SB level in Group 2, compared to that in Group 1. Moreover, we observed a
      significantly higher MDA and SB level in Group 3, vs. that in Group 1, but SB
      level was lower in Group 3 than in Group 2. Melatonin, PTU and NAC reduced CD;
      PTU, AMB diminished MDA and MEL, AMB lowered SB levels as compared to Group 3. In
      Experiment II, we observed significantly higher MDA and SB level in Group 2, vs.
      that in Group 1. Melatonin, AMB and NAC decreased MDA and SB level, when compared
      to Group 2 but PTU elevated MDA and SB level vs. that in Group 1. CONCLUSIONS: 1)
      L-T4 suppresses LPO, 2) MEL, AMB and NAC protect against LPO, 3) PTU is an
      antioxidant in thyreotoxicosis, however, when administered alone, it enhances
      LPO, 4) stress accelerate LPO.

PMID- 20150866
TI  - Lack of short-wavelength light during the school day delays dim light melatonin
      onset (DLMO) in middle school students.
AB  - OBJECTIVE: Circadian timing affects sleep onset. Delayed sleep onset can reduce
      sleep duration in adolescents required to awake early for a fixed school
      schedule. The absence of short-wavelength ("blue") morning light, which helps
      entrain the circadian system, can hypothetically delay sleep onset and decrease
      sleep duration in adolescents. The goal of this study was to investigate whether
      removal of short-wavelength light during the morning hours delayed the onset of
      melatonin in young adults. METHODS: Dim light melatonin onset (DLMO) was measured
      in eleven 8th-grade students before and after wearing orange glasses, which
      removed short-wavelength light, for a five-day school week. RESULTS: DLMO was
      significantly delayed (30 minutes) after the five-day intervention, demonstrating
      that short-wavelength light exposure during the day can be important for
      advancing circadian rhythms in students. CONCLUSIONS: Lack of short-wavelength
      light in the morning has been shown to delay the circadian clock in controlled
      laboratory conditions. The results presented here are the first to show, outside
      laboratory conditions, that removal of short-wavelength light in the morning
      hours can delay DLMO in 8th-grade students. These field data, consistent with
      results from controlled laboratory studies, are directly relevant to lighting
      practice in schools.

PMID- 20150867
TI  - The serotonin transporter gene (5-HTT) variant and psychiatric disorders: review
      of current literature.
AB  - Both serotonin and the serotonin transporter, which transports the
      neurotransmitter serotonin from synaptic spaces into presynaptic neurons, play an
      important role in the pathophysiology of several psychiatric disorders. Mutations
      associated with the serotonin transporter gene may result in changes in serotonin
      transporter function. The serotonin transporter gene promoter variant, consisting
      of a long (L) and a short (S) variant, is one of the major factors which
      contribute to the etiology of many psychiatric disorders. In this regard, many
      studies have been published on association of this variant with various
      psychiatric disorders. This repeat length variant in the promoter region of this
      gene has been shown to affect the rate of serotonin uptake and may play a role in
      post-traumatic stress disorder and depression-susceptibility in people
      experiencing emotional trauma. Associations between a functional variant in the
      serotonin transporter anxiety-related personality traits were found, as well as
      the risk of developing depression, alcoholism or suicidal behavior. Understanding
      of possible associations of these variants and psychiatric disorders would bring
      progress in principles and treatment of many disorders.

PMID- 20150868
TI  - Serum leptin is correlated to high turnover in osteoporosis.
AB  - OBJECTIVE: Clinical data have suggested that obesity protects against
      osteoporosis. Leptin, mainly secreted by white adipose tissue, might be involved
      by mediating an effect on bone metabolism. This study was conducted to
      investigate a possible relationship of leptin and bone turn-over in
      postmenopausal women with osteoporosis. METHODS: We measured bone mineral density
      (BMD), serum leptin levels and markers of bone metabolism, including osteocalcin
      and cross-laps in 44 patients with osteoporosis. The main group consisted of 32
      postmenopausal women. RESULTS: Mean serum leptin was 13.1 microg/L and showed no
      statistically significant difference to the levels measured in a collective of
      normal persons adjusted for age and BMI. When related to serum cross-laps as
      markers of bone resorption, a positive correlation (p<0.05) was observed, whereas
      no correlation with osteocalcin could be seen. CONCLUSIONS: A dual control of
      bone formation by leptin is assumed: This involves local mechanisms acting on
      osteoblasts and a central inhibitory effect on bone metabolism via a hypothalamic
      relay. Our data indicate that the net effect of circulating leptin may cause bone
      loss and is significantly related to high-turnover serum bone markers, at least
      in postmenopausal women with osteoporosis.

PMID- 20150869
TI  - Alteration of circulating Placental Leucine Aminopeptidase (P-LAP) activity in
      preeclampsia.
AB  - OBJECTIVE: Placental Leucine Aminopeptiadse (P-LAP) also known as oxytocinase, is
      secreted by syncytiotrophoblast and increases gradually during pregnancy until
      delivery. It is a regulator of uterine contractions, of vascular resistance and
      of volume of the retroplacental blood pool. Recently, it was shown that it could
      also regulate metalloproteinase 9 activity and thus, invasiveness of
      trophoblastic cells. Since development of preeclampsia could be initiated by
      decreased cytotrophoblastic invasion of spiral arterioles and a reduced
      uteroplacental perfusion, we speculate that circulating P-LAP activity could be
      decreased during preeclampsia. MATERIALS AND METHODS: Case-control study was
      evaluated in 84 women. P-LAP activity was measured in n=51 healthy pregnant women
      at term, and compared with n=16 normotensive women delivering preterm and n=17
      women diagnosed with pre-eclampsia. P-LAP activity was determined by colorimetry
      in plasma samples using L-Leucine-p-nitroanilide as substrate. RESULTS: P-LAP
      activity was significantly lower in sera of preeclamptic women (0.91+/-0.122
      mDO/min) as compared to normotensive controls (1.41+/-0.103 mDO/min; p=0.003)
      irrespective of time of delivery. CONCLUSIONS: These findings confirm the
      probable involvement of P-LAP in trophoblast invasion and development of
      preeclampsia.

PMID- 20150870
TI  - Centrally administered ascorbic acid induces antidiuresis, natriuresis and
      neurohypophyseal hormone release in rats.
AB  - OBJECTIVE: Ascorbic acid represents one of the most important antioxidants and
      neuromodulators, and plays an important role in the cerebral system. In the
      present study, we investigated the central effect of ascorbic acid on fluid
      regulation and electrolyte homeostasis. METHODS: Male Wistar rats were implanted
      with stainless steel cannulas into the lateral ventricle, and sodiun excretion
      and urinary volume were measured after intracerebroventricular (i.c.v.) injection
      of ascorbic acid (200 or 600 nmol/rat). In another set of experiments,
      vasopressin and oxytocin plasma levels were evaluated 10, 20 and 30 minutes after
      ascorbic acid i.c.v. injection. RESULTS: The administration of ascorbic acid to
      conscious rats resulted in a significant decrease in urinary volume and an
      increase in the renal excretion of sodium, with a concomitant increase in the
      plasma levels of vasopressin and oxytocin. CONCLUSIONS: These results suggest
      that ascorbic acid may play a significant role in the central regulation of fluid
      and electrolyte homeostasis.

PMID- 20150871
TI  - Variations in critical morphine biosynthesis genes and their potential to
      influence human health.
AB  - Endogenous morphine has been detected in human tissues from the vascular, immune
      and nervous systems. The genes/enzymes (CYP2D6, COMT and PNMT) that are involved
      in the biosynthesis of morphine have variations that affect their functionality.
      Some of these variations are the result of single nucleotide polymorphisms of DNA
      sequences. This review highlights some of the functional differences in the
      critical enzymes required for the biosynthesis of morphine that may affect human
      health. These variations have been shown to change the way animals react to
      stressors, perceive pain and behave. The presence of morphine signaling in almost
      all organ systems suggests that it is most likely playing a role in maintaining
      the health and promoting the normal functioning of these physiological systems.

PMID- 20150872
TI  - The importance of alpha-1 antitrypsin (alpha1-AT) and neopterin serum levels in
      the evaluation of non-small cell lung and prostate cancer patients.
AB  - OBJECTIVE: Increased serum levels of alpha-1 antitrypsin (alpha1-AT) and
      neopterin were observed in many diseases including different types of cancer. The
      aim of this work is to determine alpha1-AT and neopterin serum levels in newly
      diagnosed untreated non-small cell lung and prostate cancer patients and to test
      their relation to cancer staging. METHODS: Radial Immunodiffusion and ELISA
      methods were used to determine alpha1-AT and neopterin serum levels,
      consequently. RESULTS: alpha1-AT and neopterin mean serum levels were found to be
      elevated in non-small-cell lung and prostate cancer patients. In non-small cell
      lung cancer patients alpha1-AT was 454.5+/-129.2 mg/dL (p<0.0005) and neopterin
      was 7.9+/-4.2 ng/mL (p<0.0005). In prostate cancer patients alpha1-AT was 462.7+/
      116.9 mg/dL (p<0.0005) and neopterin was 8.1+/-3.1 ng/mL (p<0.0005). These
      elevated levels were significantly correlated with the stage of cancer. The mean
      serum level of alpha1-AT in stages I, II, III, and IV among non-small cell lung
      cancer patients were 305.1, 453.6, 490.3 and 616.0 mg/dL respectively, and the
      mean serum levels for neopterin were 4.0, 7.0, 8.1 and 14.9 ng/mL,
      correspondingly. The mean serum level of alpha1-AT in stages A, B, C, and D among
      prostate cancer patients were 342.9, 418.5, 467.8 and 593.5 mg/dL respectively
      and the mean serum levels for neopterin were 4.9, 6.6, 8.7 and 11.6 ng/mL,
      correspondingly. CONCLUSIONS: Based on the above mentioned findings alpha1-AT and
      neopterin serum levels should be considered in the follow up as well as in the
      prognosis of cancer patients.

PMID- 20150873
TI  - Elevated urine levels of bufotenine in patients with autistic spectrum disorders
      and schizophrenia.
AB  - OBJECTIVE: Previous studies have suggested that the endogeneous psychotomimetic
      molecule bufotenine (N-N-dimethyl-5-idroxytryptamine) may play a role in the
      pathogenesis of severe mental disorders. The potential association of bufotenine
      with the clinical features of autism and schizophrenia is not entirely
      understood. In this study, we measured urinary levels of bufotenine in subjects
      with autistic spectrum disorder (ASD), schizophrenia and healthy comparison
      subjects free of psychiatric symptoms. We also sought to assess whether urine
      concentrations of this molecule may be associated with the clinical
      characteristics of psychiatric patients. DESIGN: Urine bufotenine levels were
      measured using a high-performance liquid chromatography-mass spectrometry (HPLC
      MS) assay in young adults with severe ASD (n=15), patients with schizophrenia
      (n=15), and healthy control subjects (n=18). The Vineland Adaptive Behavior Scale
      was used to measure adaptive behaviors in ASD individuals. The Brief Psychiatric
      Rating Scale (BPRS) was used for patients with schizophrenia. RESULTS: Urine
      bufotenine levels were significantly higher in ASD subjects (3.30 +/- 0.49
      microg/L, p<0.05) and patients with schizophrenia (4.39 +/- 0.43 microg/L,
      p<0.001) compared with controls (1.53 +/- 0.30 microg/L). Among patients with
      ASD, there was a significant positive correlation between urine bufotenine and
      hyperactivity scores on the Vineland Adaptive Behavior Scale (r=0.479, p<0.05).
      No other associations were detected. CONCLUSIONS: Our results indicate that
      elevated urine levels of the endogeneous psychotomimetic molecule bufotenine may
      play a role in ASD and schizophrenia, and can be correlated with hyperactivity
      scores in autism.

PMID- 20150874
TI  - Isl-1 down-regulates DRG cell proliferation during chicken embryo development.
AB  - OBJECTIVE: Protein Isl-1 RNA interference and over expression in early chicken
      embryo dorsal root ganglia (DRG) were used to investigate the function of Isl-1
      in DRG cell proliferation. METHODS: Isl-1 targeted shRNA expression vector and
      Isl-1 over-expression vector were transfected into chicken embryo DRG by in ovo
      electroporation. Then, the DRG proliferation rate was detected by BrdU
      immunohistochemistry. RESULTS: The rate of DRG cell proliferation increased after
      Isl-1 knock-down and decreased after Isl-1 over-expression. CONCLUSIONS: In this
      study, we found that Isl-1 negatively modulates DRG cell proliferation.

PMID- 20150875
TI  - Edwards syndrome in a 6-year old girl.
AB  - Trisomy 18 (Edwards syndrome - ES) is the second most common trisomy. It occurs
      in 1/3 000 to 1/8 000 births. ES is a cause of numerous developmental disorders
      and malformations. The median life span of children with ES is about 2 weeks and
      only 5%-10% will survive their first year of life. The report presents a case of
      a 6-year-old girl with ES.

PMID- 20150876
TI  - Elevation of growth hormone secretagogue receptor type 1a mRNA expression in
      human growth hormone-secreting pituitary adenoma harboring G protein alpha
      subunit mutation.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      the ghrelin or GHSR-1a mRNA levels and clinical characteristics and to confirm
      the effect of gsp mutations on ghrelin/GHSR-1a system in human GH-secreting
      pituitary adenomas. METHODS: The expression levels of ghrelin, GHSR-1a mRNA were
      determined by SYBR green real-time fluorescent quantitative PCR. The gsp
      mutations in 43 cases of human GH-secreting pituitary adenomas were detected
      using PCR-DNA direct sequencing analysis. Clinical data were obtained from the
      medical records of 43 acromegalic patients who had GH and IGF-1 assays in the
      same laboratory. RESULTS: The expression of GHSR-1a correlated positvely with
      tumor size (R=0.411, p=0.006) and invasiveness (p<0.05). In contrast, ghrelin
      mRNA levels correlated positively only with tumor size (R=0.331, p=0.030) but not
      with tumor invasiveness (p>0.05). The expression level of GHSR-1a mRNA was
      significantly higher in gsp positive adenomas than in negative adenomas (p<0.05).
      Whereas, there was no significant difference in the expression of ghrelin mRNA
      between gsp mutation-positive and -negative adenomas (p>0.05). Additionally there
      was a significant positve correlation between the ghrelin and GHSR-1a mRNA
      expression levels in gsp-positive (R=0.553, p=0.040) or -negative adenomas
      (R=0.489, p=0.007). CONCLUSIONS: GHSR-1a correlated positively with tumor size
      and invasiveness, while ghrelin correlated positively only with tumor size. Gsp
      mutations may upregulate the expression of GHSR-1a mRNA and have no effect on
      ghrelin mRNA levels in human GH-secreting pituitary adenomas.

PMID- 20150877
TI  - Estrogen receptor-alpha immunoreactivity in the arcuate hypothalamus of young and
      middle-aged female mice.
AB  - BACKGROUND: Changes in the neuroendocrine regulation of gonadal function, via
      altered hypothalamic sensitivity to peripheral hormones, are known to schedule
      reproductive maturation in the young and influence reproductive senescence.
      Estrogen (E) is a key hormone in this process. While changes in circulating
      levels of E over the life span are well documented, less is known about the
      corresponding changes in E sensitivity over the lifespan, especially during
      middle-age, when the initial signs of reproductive senescence emerge. OBJECTIVE:
      Taking Estrogen Receptor (ER)-alpha-immunoreactive cells as an index of
      hypothalamic sensitivity to E, this investigation aims to quantify alterations
      occurring at middle age in comparison to young age. METHODS: We counted ER-alpha
      immunoreactive (IR) cells in the Arcuate hypothalamus of 6-week-old (young) and
      18-month-old (middle-aged) C57BL/6J female mice, sacrificed at vaginal opening
      and diestrous, respectively. An automated imaging microscopy system (AIMS) was
      employed to generate counts of ER-alpha-IR cells for each sampled section of the
      Arcuate nucleus (ARC). RESULTS: This study shows a 21% reduction in the number of
      ER-alpha-IR cells and an 18% reduction in total ARC cell populations with aging.
      However, the calculated percentage of ER-alpha IR cells is similar in both young
      and middle aged mice, 30% and 29%, respectively. CONCLUSIONS: Both ER-alpha IR
      cell populations and total cell populations within the ARC hypothalamus decline
      by middle age in comparison to young age. Despite such a significant decrease in
      ER-alpha immunoreactive and total cells, both young and middle age mice maintain
      a similar ratio of ER-alpha IR cells to total cells in the ARC hypothalamus.

PMID- 20150878
TI  - Benefits of examination by post mortem performed magnetic resonance imaging of
      foetus: haemorrhage in germinal matrix.
AB  - Post mortem magnetic resonance imaging is demonstrated as a supplementary method
      to classic pathological-anatomical autopsy in determining anomalies of the
      foetus. Frequently it plays a key role; primarily where the possibilities of
      performing autopsy are somehow limited (autolysis, ventricular dilatation).
      Specification of the final diagnosis subsequently enables us to improve prenatal
      diagnostics, both by means of magnetic resonance imaging and primarily by
      correlation with the prenatal ultrasound scan; this feedback improves the later
      method. This case report demonstrated that post mortem magnetic resonance
      imaging, in contrast with prenatal ultrasound examination, showed extensive
      haemorrhage in the germinal matrix, and also illustrated indirect symptoms
      testifying to agenesis of the corpus callosum. Prenatal ultrasound examination
      showed only hydrocephalus and absence of septum pellucidum. Pathological
      anatomical autopsy of the brain was insufficient with regard to advanced
      autolysis and brain haemorrhage.

PMID- 20150879
TI  - Single nucleotide polymorphism of the KIBRA gene in recurrent depressive
      disorders.
AB  - OBJECTIVE: Depression is a disease of multifactor background. Episodic memory
      dysfunction is one of depression characterising disturbances, which may lead to
      its onset and development. Memory processes are controlled by a number of extra-
      and intracellular mechanisms. KIBRA, a newly discovered protein, belonging to
      signal transduction proteins, participates in the control of episodic memory. The
      presented study was designed to assess correlation between single nucleotide
      polymorphism (SNP) T/C (rs17070145) of the KIBRA gene and the risk of recurrent
      depressive disorder (DD). METHODS: The study was carried out in a group of 181
      patients with recurrent DD and 149 healthy control subjects. Genotyping was
      conducted by polymerase chain reaction (PCR)/restriction fragment length
      polymorphism (RLFP) method. RESULTS: TThe obtained results have revealed no
      significant correlation between the studied polymorphism and recurrent DD.
      Obtained value of the disease odds ratio (ORdis) suggests that presence of T/T
      homozygote decreases risk of development of recurrent DD, but the result was not
      statistically significant. CONCLUSIONS: Following the results, it may be
      concluded that the studied polymorphism does not influence either the onset
      mechanism or the course of recurrent DD. Even if T/C polymorphism of the KIBRA
      gene induces memory disturbances, they may be unspecific and unselective for
      recurrent DD. Further studies on the genes, which control characteristic
      processes of DD and influence their course, are demanded and mostly justified.

PMID- 20150880
TI  - The expression of atrial natriuretic peptide receptor in the mouse inner ear
      labyrinth.
AB  - OBJECTIVE: To compare the relative expression levels of NPR-A mRNA in the stria
      vascularis (StV), nonstrial tissue of the cochlear lateral wall (NSt) and
      vestibula in the mouse inner ear to determine the potential contribution of ANP
      signaling in different parts to inner ear fluid homeostasis. SETTING: Atrial
      natriuretic peptide (ANP) is a cardiac hormone known to be involved in the
      regulation of body fluid homeostasis. It is assumed that ANP might also
      participate in the regulation of inner ear fluid dynamics. ANP selectively binds
      with atrial natriuretic peptide receptor (NPR-A) to exert its physiological
      function. We have previously shown the presence of NPR-A transcripts in the mouse
      stria vascularis as well as in the nonstrial tissue of the cochlear lateral wall
      and vestibular organ by polymerase-chain reaction. METHODS: Total RNA of samples
      of stria vascularis, nonstrial tissue of the cochlear lateral wall and vestibular
      organ tissue from ears of 10 adult mice was isolated, amplified by the real-time
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) using
      consensus primers flanking a region of 127 bp at the target sequences. The brain
      of mice known to contain NPR-A was used as a positive control. The one-way
      analysis of variance, ANOVA and Student-Newman-Keuls method were performed to
      analyze the data. RESULTS: NPR-A mRNA expression was found in tissue samples of
      all the three areas. The mRNA expression level of NPR-A in the StV was higher
      than that in the NSt and vestibula (p<0.05). The difference of NPR-A mRNA
      expression level in the NSt and vestibula was not statistically significant
      (p>0.05). CONCLUSIONS: Our results suggest that the StV may be the most important
      place for ANP to regulate endolymph fluid balance via NPR-A.

PMID- 20150881
TI  - Norepinephrine modulates the effect of neuropeptides in coeliac ganglion on
      ovarian hormones release: its relationship with ovarian nitric oxide and nerve
      growth factor.
AB  - OBJECTIVE: Ovarian steroids are modulated by neural influences. In this work we
      investigate whether norepinephrine (NE) modifies the vasoactive intestinal
      peptide (VIP) or neuropeptide Y (NPY) actions in coeliac ganglion (CG) on the
      ovarian hormone release, and evaluate the participation of nitric oxide (NO),
      measured as nitrite, and of inducible nitric oxide synthetase (iNOS) protein,
      nerve growth factor (NGF) and its trkA receptor gene expression in the ovarian
      response. METHODS: The study was performed in the ex vivo CG-superior ovarian
      nerve (SON)-ovary system of rats on diestrus day 2 (D2). CG and ovary were placed
      in separate compartments connected by the SON and incubated with Krebs-Ringer
      buffer. After addition of 50 ng/ml VIP, 50 ng/ml NPY, 10-6 M NE, or a mix of
      VIP+NE or NPY+NE in ganglion, samples from the ovarian compartment were taken at
      different times throughout 180 minutes to measure progesterone, androstenedione
      and nitrite levels. RESULTS: VIP and NPY in ganglion induced an increase of
      progesterone release that was associated for VIP, but not NPY, with a decrease of
      ovarian nitrite levels, iNOS protein, and NGF/trkA receptor mRNA expression. By
      contrast, NE in ganglion decreased progesterone, an effect that was suppressed by
      addition of propranolol in ganglion, and increased nitrites/iNOS and NGF/trkA
      receptor expression in ovary. GABA A receptor antagonist bicuculline (20 muM)
      added in ovarian compartment prevented the inhibitory effect on progesterone
      caused by NE in CG. Androstenedione was not modified under neuropeptides or NE
      ganglionic stimulation. CONCLUSIONS: Finally, results from VIP+NE or NPY+NE in
      ganglion showed that ovarian response on D2 induced by VIP or NPY alone is
      moderated by the opposite action of NE, and occurs only on progesterone, the most
      sensitive steroid to neural action.

PMID- 20150882
TI  - The association between TaqI A polymorphism of ANKK1 (DRD2) gene and ADHD in the
      Czech boys aged between 6 and 13 years.
AB  - OBJECTIVE: The purpose of this study was the correlation of the combined type of
      ADHD in children and Taq IA polymorphism DRD2 gene. We hypothesized a positive
      correlation of DRD2 polymorphisms in the combined type of ADHD patients without
      co-morbidity. PATIENTS AND METHODS: Our research sample included 586 unrelated
      boys of the Czech origin aged between 6 and 13 years. The ADHD group consisted of
      269 boys and the control group consisted of 317 boys. PCR detection of the DRD2
      polymorphism was carried out by using primers, described by Grandy (Grandy et al.
      1989). RESULTS: The comparison of genotype frequencies showed statistically
      highly significant difference between the studied groups (p<0.0001). A
      statistically significant difference was also found when the allelic frequencies
      between the two groups were compared (p<0.0001), with the A1 allele having a
      4.359 fold higher risk of ADHD (Risk Ratio=4.359, 95% CI of RR=3.5753 to 5.3144,
      Odds Ratio= 7.7824; 95% CI of OR=10.315 to 13.6719). CONCLUSIONS: Our results
      presented a highly positive correlation between the combined type of ADHD without
      co-morbidity and ANKK l (DRD2) polymorphism .

PMID- 20150883
TI  - Repetitive TMS of the somatosensory cortex improves writer's cramp and enhances
      cortical activity.
AB  - Since the somatosensory system is believed to be affected in focal dystonia, we
      focused on the modulation of the primary somatosensory cortex (SI) induced by
      repetitive transcranial magnetic stimulation (rTMS) in order to improve symptoms
      of writer's cramp. Patients with writer's cramp (N=9 in the pilot study and N=11
      in the advanced study) were treated with 30-minute 1 Hz real- or sham-rTMS of the
      SI cortex every day for 5 days. Before and after rTMS, 1.5 T fMRI was examined
      during simple hand movements. While in the pilot study the rTMS coil was
      navigated over the SI cortex with a maximum of blood oxygenation-level dependent
      (BOLD) signal induced by passive movement, patients in the advanced study had the
      coil above the postcentral sulcus. After real-rTMS, 4 pilot study patients and 10
      advanced study patients experienced subjective and objective improvement in
      writing, while only minimal changes were observed after sham-rTMS. Patients
      involved in the active movement task exhibited a rTMS-induced BOLD signal
      increase bilaterally in the SI cortex, posterior parietal cortex and in the
      supplementary motor area (P<0.001 corrected). After sham-rTMS, no BOLD signal
      changes were observed. In conclusion, 1 Hz rTMS of the SI cortex can improve
      writer's cramp while increasing the cortical activity in both hemispheres.
      Handwriting improved in most patients, as well as the subjective benefit, and
      lasted for 2-3 weeks. The beneficial effects of rTMS paralleled the functional
      reorganization in the SI cortex and connected areas, reflecting the impact of
      somatosensory system on active motion control.

PMID- 20150884
TI  - Increased dopamine DRD4 receptor mRNA expression in lymphocytes of musicians and
      autistic individuals: bridging the music-autism connection.
AB  - BACKGROUND: People with autistic spectrum disorder (ASD) are affected by a long
      life disabling condition, characterized by communication deficits, severe
      impairments in social functioning, and stereotyped behaviors. Although ASD
      individuals display several problems in interactions, it has been reported that
      they may show a peculiar interest in music. Previous studies have suggested a
      pivotal role for the dopaminergic system in the psychobiology of reward,
      including the pleasure of music. DESIGN: In the present study, we sought to
      investigate dopamine DRD3 and DRD4 receptor expression in peripheral blood
      lymphocytes of adult healthy musicians and age- and gender-matched patients with
      ASD against the background hypothesis that the dopaminergic system may contribute
      a biological cause to the reward dimensions of the musical experience in both
      healthy and autistic individuals. RESULTS: ANOVA showed significant differences
      in DRD4 mRNA expression between the groups (P = 0.008). Post-hoc analysis showed
      significant differences between the control group and both musicians (P < 0.05)
      and ASD individuals (P < 0.05). No differences were found for DRD3 mRNA
      expression between the groups. CONCLUSION: Our current results provide intriguing
      preliminary evidence for a possible molecular link between dopamine DRD4
      receptor, music and autism, possibly via mechanisms involving the reward system
      and the appraisal of emotions.

PMID- 20150885
TI  - Placenta and umbilical cord blood deserve attention.
AB  - OBJECTIVES: This work follows up with our already published results concerning
      consequences of lead on prenatal and postnatal development of child in connection
      with the rise of hyperkinetic syndrome (ADHD). This disease has in children
      increasing tendency all over the world. METHODS: In our work we used a set of
      histological and histochemical methods, method of scanning electron microscopy,
      infrared spectroscopy and statistical evaluation. RESULTS: Our new method for
      proof of lead in placenta enabled us to show how lead is cumulated in
      syncytiotrophoblast. We have found release of lead from mother's erythrocytes in
      the intervillous space and receipt of lead by erythrocytes of fetus in the
      vessels of the villi of placenta. This finding enriches knowledge about relation
      between mother's erythrocytes, lead, calcium that is lead carrier,
      syncytiotrophoblast, and erythrocytes of fetus in the vessels of placental villi.
      We have proved that syncytiotrophoblast is the most frequent place for cumulation
      of lead deposits. We verified our ecomorphologic results by means of infrared
      spectroscopy in cooperation with physicists and statistically evaluated
      occurrence of ADHD in particular age categories what helps to fill gaps in
      knowledge of ADHD etiology. CONCLUSIONS: Our finding of lead in umbilical cord
      blood immediately after the child birth is forewarning against the possible rise
      of the ADHD. This finding facilitates early diagnostics and means preventing step
      against the rise, development and consequences of this disease. The obtained
      results give evidence about the serious influence of mother's dwelling in
      environment polluted with neurotoxic metal - lead on the prenatal and postnatal
      development of child.

PMID- 20150886
TI  - The neurobiology of stress management.
AB  - BACKGROUND AND OBJECTIVE: Stress is natural and belongs to life itself. To
      sustain it and even grow with it biology invented different mechanisms, since
      stress resistance is obligatory. These pathways, we surmise, can be activated and
      learned intentionally, through professional stress management training or 'mind
      body medicine', or endogenously and automatically through autoregulation. Since
      the primary goal of various stress-reducing approaches is corresponding, we
      expect to find an overlapping physiology and neurobiological principle of stress
      reduction. These common pathways, as we speculate, involve some of the very same
      signalling molecules and structures. METHODS: Concepts of stress and stress
      management are described and then associated with underlying molecular and
      neurobiological pathways. Evidence is gathered from different sources to
      substantiate the hypothesis of an overlapping neurobiological principle in stress
      autoregulation. RESULTS: Stress describes the capacity and mechanisms to sustain
      and adjust to externally or internally challenging situations. Therefore,
      organisms can rely on the endogenous ability to self-regulate stress and
      stressors, i.e., autoregulatory stress management. Stress management usually
      consists of one to all of the following instruments and activities: behavioral or
      cognitive, exercise, relaxation and nutritional or food interventions (BERN),
      including social support and spirituality. These columns can be analyzed for
      their underlying neurobiological and autoregulatory pathways, thereby revealing a
      close connection to the brain's pleasure, reward and motivation circuits that are
      particularly bound to limbic structures and to endogenous dopamine, morphine, and
      nitric oxide (NO) signalling. Within this work, we demonstrate the existence of
      opioid, opiate, dopamine and related pathways for each of the selected stress
      management columns. DISCUSSION: Stress management techniques may possess specific
      and distinct physiological effects. However, beneficial behaviors and strategies
      to overcome stress are, as a more general principle, neurobiologically rewarded
      by pleasure induction, yet positively and physiologically amplified and
      reinforced, and this seems to work via dopamine, endorphin and morphine release,
      apart from other messenger molecules. These latter effects are unspecific,
      however, down-regulatory and clearly stress-reducing by their nature.
      CONCLUSIONS: There seems to exist a common neurobiological mechanism, i.e.,
      limbic autoregulation, that involves dopamine, morphine and other endogenous
      signalling molecules, e.g., other opioid receptor agonists, endocannabinoids,
      oxytocin or serotonin, many of which act via NO release, and this share seems to
      be of critical importance for the self-regulation and management of stress:
      stress management is an endogenous potential.

PMID- 20150887
TI  - Update: mumps outbreak - New York and New Jersey, June 2009-January 2010.
AB  - State and local health departments, in collaboration with CDC, continue to
      investigate a mumps outbreak that began in New York in June 2009. The index case
      occurred in a boy aged 11 years who had returned on June 17 from a trip to the
      United Kingdom, where approximately 7,400 reports of laboratory-confirmed mumps
      were received by the Health Protection Agency in 2009. He then attended a New
      York summer camp for tradition-observant Jewish boys, where he became symptomatic
      on June 28. Subsequently, other camp attendees and a staff member were reported
      to have mumps, and transmission continued in multiple locations when the camp
      attendees returned home. As of January 29, 2010, a total of 1,521 cases had been
      reported, with onset dates from June 28, 2009, through January 29, 2010, a
      substantial increase from the 179 cases reported as of October 30, 2009. The
      outbreak has remained confined primarily to the tradition-observant Jewish
      community, with <3% of cases occurring among persons outside the community. The
      largest percentage of cases (61%) has occurred among persons aged 7-18 years, and
      76% of the patients are male. Among the patients for whom vaccination status was
      reported, 88% had received at least 1 dose of mumps-containing vaccine, and 75%
      had received 2 doses. This is the largest mumps outbreak that has occurred in the
      United States since 2006. Although mumps vaccination alone was not sufficient to
      prevent this outbreak, maintaining high measles, mumps, and rubella (MMR)
      vaccination coverage remains the most effective way to prevent outbreaks and
      limit their size when they occur.

PMID- 20150888
TI  - Transmission of yellow fever vaccine virus through breast-feeding - Brazil, 2009.
AB  - In April, 2009, the state health department of Rio Grande do Sul, Brazil, was
      notified by the Cachoeira do Sul municipal health department of a case of
      meningoencephalitis requiring hospitalization in an infant whose mother recently
      had received yellow fever vaccine during a postpartum visit. The Field
      Epidemiology Training Program of the Secretariat of Surveillance in Health of the
      Brazilian Ministry of Health assisted state and municipal health departments with
      an investigation. This report summarizes the results of that investigation, which
      determined that the infant acquired yellow fever vaccine virus through breast
      feeding. The mother reported 2 days of headache, malaise, and low fever occurring
      5 days after receipt of yellow fever vaccine. The infant, who was exclusively
      breast-fed, was hospitalized at age 23 days with seizures requiring continuous
      infusion of intravenous anticonvulsants. The infant received antimicrobial and
      antiviral treatment for meningoencephalitis. The presence of 17DD yellow fever
      virus was detected by reverse transcription--polymerase chain reaction (RT-PCR)
      in the infant's cerebrospinal fluid (CSF); yellow fever--specific immunoglobulin
      M (IgM) antibodies also were present in serum and CSF. The infant recovered
      completely, was discharged after 24 days of hospitalization, and has had normal
      neurodevelopment and growth through age 6 months. The findings in this report
      provide documentation that yellow fever vaccine virus can be transmitted via
      breast-feeding. Administration of yellow fever vaccine to breast-feeding women
      should be avoided except in situations where exposure to yellow fever viruses
      cannot be avoided or postponed.

PMID- 20150889
TI  - Progress in immunization information systems - United States, 2008.
AB  - Immunization information systems (IISs) are confidential, computerized
      information systems that collect and consolidate vaccination data from multiple
      health-care providers, generate reminder and recall notifications, and assess
      vaccination coverage within a defined geographic area. A CDC program goal for
      2010 is to achieve >or=95% participation in an IIS (defined as having two or more
      recorded vaccinations) among children aged <6 years. To monitor progress toward
      this goal, CDC annually surveys immunization grantees in 50 states, five cities,
      and the District of Columbia, using the Immunization Information Systems Annual
      Report (IISAR). All 56 grantees were asked to complete the IISAR; 52 did so for
      2008. This report highlights results from the 2008 IISAR, which indicated that
      75% of all U.S. children aged <6 years (approximately 18 million children)
      participated in an IIS in 2008, an increase from 65% in 2006. The majority of
      grantees (82%) reported that their IIS had the capacity to track vaccinations for
      persons of all ages, compared with 70% in 2006. Data-quality measures of
      timeliness and completeness indicated that in 2008, 67% of IIS data were received
      and processed within 30 days of vaccine administration, and data were reported
      for six of 17 core data elements in >or=90% of IIS records (both measures are
      similar to 2006 results). Increased provider use of electronic health record
      systems can benefit IISs and their users by producing immunization records that
      are more timely and complete.

PMID- 20150890
TI  - Obtaining hemocytes from the Hawaiian bobtail squid Euprymna scolopes and
      observing their adherence to symbiotic and non-symbiotic bacteria.
AB  - Studies concerning the role of the immune system in mediating molecular signaling
      between beneficial bacteria and their hosts have, in recent years, made
      significant contributions to our understanding of the co-evolution of eukaryotes
      with their microbiota. The symbiotic association between the Hawaiian bobtail
      squid, Euprymna scolopes and the bioluminescent bacterium Vibrio fischeri has
      been utilized as a model system for understanding the effects of beneficial
      bacteria on animal development. Recent studies have shown that macrophage-like
      hemocytes, the sole cellular component of the squid host's innate immune system,
      likely play an important role in mediating the establishment and maintenance of
      this association. This protocol will demonstrate how to obtain hemocytes from E.
      scolopes and then use these cells in bacterial binding assays. Adult squid are
      first anesthetized before hemolymph is collected by syringe from the main
      cephalic blood vessel. The host hemocytes, contained in the extracted hemolymph,
      are adhered to chambered glass coverslips and then exposed to green fluorescent
      protein-labeled symbiotic Vibrio fischeri and non-symbiotic Vibrio harveyi. The
      hemocytes are counterstained with a fluorescent dye (Cell Tracker Orange,
      Invitrogen) and then visualized using fluorescent microscopy.

PMID- 20150891
TI  - Influence of leptin, adiponectin, and resistin on the association between
      abdominal adiposity and arterial stiffness.
AB  - BACKGROUND: Adiposity is associated with arterial stiffness, and both adiposity
      and arterial stiffness independently predict morbidity and mortality. Because
      adipocytes account for most adipokine production, the objectives of this study
      were to examine the influence of adipokines such as leptin, adiponectin, and
      resistin on the relationship between abdominal adiposity and arterial stiffness.
      METHODS: This is a cross-sectional analysis of data from the Baltimore
      Longitudinal Study of Aging (BLSA). Adiposity was measured as kilograms of
      abdominal adipose tissue using dual-energy X-ray absorptiometry (DXA). Arterial
      stiffness was assessed as carotid-femoral pulse wave velocity (PWV). Leptin,
      adiponectin, and resistin were assayed in fasting serum samples. The influence of
      adipokines on the relationship between adiposity and arterial stiffness by
      adipokines was examined using standard mediation pathway analysis. RESULTS: Among
      749 participants ages 26-96 years (mean age 67, 52% men, 27% black), abdominal
      adiposity was positively associated with PWV (relative ratio (RR) = 1.04, P =
      0.02), after adjusting for potential confounders but was attenuated and no longer
      significant after adjusting for leptin (RR = 0.99, P = 0.77). The relationship
      between adiposity and PWV was not substantially influenced by adiponectin (RR =
      1.03, P = 0.06) or resistin (RR = 1.05, P = 0.010). Leptin (RR = 1.02, P <
      0.001), resistin (RR = 0.92, P < 0.0001), and adiponectin (RR = 0.97, P = 0.004),
      but not abdominal adiposity (RR = 1.00, P = 0.94), retained significant
      associations with PWV when adjusting for each other and confounders. CONCLUSIONS:
      Our findings are consistent with the hypothesis that leptin explains, in part,
      the observed relationship between abdominal adiposity and arterial stiffness.
      Adiponectin, leptin, and resistin are independent correlates of PWV.

PMID- 20150892
TI  - Genetic analysis of Ras signalling pathways in cell proliferation, migration and
      survival.
AB  - We have used mouse embryonic fibroblasts (MEFs) devoid of Ras proteins to
      illustrate that they are essential for proliferation and migration, but not for
      survival, at least in these cells. These properties are unique to the Ras
      subfamily of proteins because ectopic expression of other Ras-like small GTPases,
      even when constitutively active, could not compensate for the absence of Ras
      proteins. Only constitutive activation of components of the Raf/Mek/Erk pathway
      was sufficient to sustain normal proliferation and migration of MEFs devoid of
      Ras proteins. Activation of the phosphatidylinositol 3-kinase (PI3K)/PTEN/Akt and
      Ral guanine exchange factor (RalGEF)/Ral pathways, either alone or in
      combination, failed to induce proliferation or migration of Rasless cells,
      although they cooperated with Raf/Mek/Erk signalling to reproduce the full
      response mediated by Ras signalling. In contrast to current hypotheses, Ras
      signalling did not induce proliferation by inducing expression of D-type Cyclins.
      Rasless MEFs had normal levels of Cyclin D1/Cdk4 and Cyclin E/Cdk2. However,
      these complexes were inactive. Inactivation of the pocket proteins or knock down
      of pRb relieved MEFs from their dependence on Ras signalling to proliferate.

PMID- 20150893
TI  - VHS domains of ESCRT-0 cooperate in high-avidity binding to polyubiquitinated
      cargo.
AB  - VHS (Vps27, Hrs, and STAM) domains occur in ESCRT-0 subunits Hrs and STAM, GGA
      adapters, and other trafficking proteins. The structure of the STAM VHS domain
      ubiquitin complex was solved at 2.6 A resolution, revealing that determinants for
      ubiquitin recognition are conserved in nearly all VHS domains. VHS domains from
      all classes of VHS-domain containing proteins in yeast and humans, including both
      subunits of ESCRT-0, bound ubiquitin in vitro. ESCRTs have been implicated in the
      sorting of Lys63-linked polyubiquitinated cargo. Intact human ESCRT-0 binds Lys63
      linked tetraubiquitin 50-fold more tightly than monoubiquitin, though only 2-fold
      more tightly than Lys48-linked tetraubiquitin. The gain in affinity is attributed
      to the cooperation of flexibly connected VHS and UIM motifs of ESCRT-0 in avid
      binding to the polyubiquitin chain. Mutational analysis of all the five ubiquitin
      binding sites in yeast ESCRT-0 shows that cooperation between them is required
      for the sorting of the Lys63-linked polyubiquitinated cargo Cps1 to the vacuole.

PMID- 20150894
TI  - Force generated by actomyosin contraction builds bridges between adhesive
      contacts.
AB  - Extracellular matrices in vivo are heterogeneous structures containing gaps that
      cells bridge with an actomyosin network. To understand the basis of bridging, we
      plated cells on surfaces patterned with fibronectin (FN)-coated stripes separated
      by non-adhesive regions. Bridges developed large tensions where concave cell
      edges were anchored to FN by adhesion sites. Actomyosin complexes assembled near
      those sites (both actin and myosin filaments) and moved towards the centre of the
      non-adhesive regions in a treadmilling network. Inhibition of myosin-II (MII) or
      Rho-kinase collapsed bridges, whereas extension continued over adhesive areas.
      Inhibition of actin polymerization (latrunculin-A, jasplakinolide) also collapsed
      the actomyosin network. We suggest that MII has distinct functions at different
      bridge regions: (1) at the concave edges of bridges, MIIA force stimulates actin
      filament assembly at adhesions and (2) in the body of bridges, myosin cross-links
      actin filaments and stimulates actomyosin network healing when breaks occur. Both
      activities ensure turnover of actin networks needed to maintain stable bridges
      from one adhesive region to another.

PMID- 20150895
TI  - Tonic ubiquitylation controls T-cell receptor:CD3 complex expression during T
      cell development.
AB  - Expression of the T-cell receptor (TCR):CD3 complex is tightly regulated during T
      cell development. The mechanism and physiological role of this regulation are
      unclear. Here, we show that the TCR:CD3 complex is constitutively ubiquitylated
      in immature double positive (DP) thymocytes, but not mature single positive (SP)
      thymocytes or splenic T cells. This steady state, tonic CD3 monoubiquitylation is
      mediated by the CD3varepsilon proline-rich sequence, Lck, c-Cbl, and SLAP, which
      collectively trigger the dynamin-dependent downmodulation, lysosomal
      sequestration and degradation of surface TCR:CD3 complexes. Blocking this tonic
      ubiquitylation by mutating all the lysines in the CD3 cytoplasmic tails
      significantly upregulates TCR levels on DP thymocytes. Mimicking
      monoubiquitylation by expression of a CD3zeta-monoubiquitin (monoUb) fusion
      molecule significantly reduces TCR levels on immature thymocytes. Moreover,
      modulating CD3 ubiquitylation alters immunological synapse (IS) formation and Erk
      phosphorylation, thereby shifting the signalling threshold for positive and
      negative selection, and regulatory T-cell development. Thus, tonic TCR:CD3
      ubiquitylation results in precise regulation of TCR expression on immature T
      cells, which is required to maintain the fidelity of T-cell development.

PMID- 20150896
TI  - Structure of a double ubiquitin-like domain in the talin head: a role in integrin
      activation.
AB  - Talin is a 270-kDa protein that activates integrins and couples them to
      cytoskeletal actin. Talin contains an N-terminal FERM domain comprised of F1, F2
      and F3 domains, but it is atypical in that F1 contains a large insert and is
      preceded by an extra domain F0. Although F3 contains the binding site for beta
      integrin tails, F0 and F1 are also required for activation of beta1-integrins.
      Here, we report the solution structures of F0, F1 and of the F0F1 double domain.
      Both F0 and F1 have ubiquitin-like folds joined in a novel fixed orientation by
      an extensive charged interface. The F1 insert forms a loop with helical
      propensity, and basic residues predicted to reside on one surface of the helix
      are required for binding to acidic phospholipids and for talin-mediated
      activation of beta1-integrins. This and the fact that basic residues on F2 and F3
      are also essential for integrin activation suggest that extensive interactions
      between the talin FERM domain and acidic membrane phospholipids are required to
      orientate the FERM domain such that it can activate integrins.

PMID- 20150899
TI  - Beyond the BMI: the search for better guidelines for bariatric surgery.
AB  - The application of the BMI of > or =35 as the major prerequisite for access to
      bariatric surgery is no longer appropriate because the index, now incorporated in
      the requirements of Medicare, Medicaid and most private carriers, does not
      reflect the degree or distribution of adiposity, it discriminates unfairly on the
      basis of gender, race, age, fitness, and body fat composition. Further, with
      increasing evidence that bariatric surgery can also induce full and durable
      remission of such comorbidities as type 2 diabetes even in patients with BMIs
      <30, new guidelines must be pursued.

PMID- 20150898
TI  - Regulation of clathrin adaptor function in endocytosis: novel role for the SAM
      domain.
AB  - During clathrin-mediated endocytosis, adaptor proteins play central roles in
      coordinating the assembly of clathrin coats and cargo selection. Here we
      characterize the binding of the yeast endocytic adaptor Sla1p to clathrin through
      a variant clathrin-binding motif that is negatively regulated by the Sla1p SHD2
      domain. The crystal structure of SHD2 identifies the domain as a sterile alpha
      motif (SAM) domain and shows a propensity to oligomerize. By co
      immunoprecipitation, Sla1p binds to clathrin and self-associates in vivo.
      Mutations in the clathrin-binding motif that abolish clathrin binding and
      structure-based mutations in SHD2 that impede self-association result in
      endocytosis defects and altered dynamics of Sla1p assembly at the sites of
      endocytosis. These results define a novel mechanism for negative regulation of
      clathrin binding by an adaptor and suggest a role for SAM domains in clathrin
      mediated endocytosis.

PMID- 20150900
TI  - Tissue-specificity and ethnic diversity in obesity-related risk of cancer may be
      explained by variability in insulin response and insulin signaling pathways.
AB  - Obesity is a predisposing risk factor for several chronic diseases. The link
      between obesity and cancer appears to be particularly complex. Notably only the
      risk for development of specific cancers appear to be affected. Moreover, the
      obesity-related risk of cancer is very different across ethnic groups. African
      Americans appear particularly prone, whereas Hispanics appear to be relatively
      protected. Obesity is associated with increased levels of circulating insulin.
      These levels of elevated insulin may serve to promote proliferation of fat cells
      to accommodate the elevated nutrient flux. However, elevated levels of insulin
      may be a major mediating factor influencing cancer risk. This hypothesis alone
      cannot explain the complexity of the phenomenon. We suggest here that the
      different insulin responses to obesity of different ethnic groups may explain
      their different risk profiles. Moreover, we speculate that tissue-specific
      variations in the insulin signaling pathways may underlie their differential
      susceptibility to tumorigenesis in the face of elevated obesity. Elevated cancer
      risk may be an unwanted side effect of insulin responding to elevated nutrient
      flux in the obese which it serves to proliferate fat cells that provide a
      location for storage of ingested fat, which consequently prevents ectopic fat
      storage. Hence, while Hispanics may be protected from cancer risk in obesity
      because of their lower insulin response, they have an elevated risk of fatty
      liver disease. Reduction of insulin levels in obesity as a strategy to reduce
      cancer risk may pose additional problems unless it is combined also with
      interventions that aim to limit nutrient influx.

PMID- 20150897
TI  - New insights into an old story: Agrobacterium-induced tumour formation in plants
      by plant transformation.
AB  - Agrobacterium tumefaciens causes tumour formation in plants. Plant signals induce
      in the bacteria the expression of a range of virulence (Vir) proteins and the
      formation of a type IV secretion system (T4SS). On attachment to plant cells, a
      transfer DNA (T-DNA) and Vir proteins are imported into the host cells through
      the bacterial T4SS. Through interaction with a number of host proteins, the Vir
      proteins suppress the host innate immune system and support the transfer, nuclear
      targeting, and integration of T-DNA into host cell chromosomes. Owing to
      extensive genetic analyses, the bacterial side of the plant-Agrobacterium
      interaction is well understood. However, progress on the plant side has only been
      achieved recently, revealing a highly complex molecular choreography under the
      direction of the Vir proteins that impinge on multiple processes including
      transport, transcription, and chromosome status of their host cells.

PMID- 20150901
TI  - Will work for snack food: the association of BMI and snack reinforcement.
AB  - It has been suggested that for overweight and obese individuals high-calorie
      foods are more reinforcing than for normal-weight individuals. It has already
      been shown that in contrast to sedentary activities, snack food is more
      reinforcing for obese women, relative to normal-weight women. However, it is
      unclear whether overweight/obese individuals are more sensitive to the
      reinforcing value of food in general or more specifically to the reinforcing
      value of high-calorie foods. This was tested in the present study, with
      overweight/obese and normal-weight individuals performing a concurrent schedules
      task, which measures how hard someone is prepared to work for high-calorie snacks
      compared to low-calorie foods (e.g., fruits, vegetables), when both foods are
      equally liked. By gradually increasing the amount of work required to earn
      snacks, the relative-reinforcing value of snacks was determined. As hypothesized,
      overweight/obese individuals work harder for high-calorie snacks compared to
      normal-weight individuals.

PMID- 20150902
TI  - 25-Hydroxyvitamin D concentration correlates with insulin-sensitivity and BMI in
      obesity.
AB  - The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25
      hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor
      for type 2 diabetes, although its relation with insulin-sensitivity is not well
      investigated. Thus, we aimed to investigate the relationship between 25(OH)D
      concentration and insulin-sensitivity, using the glucose clamp technique. In
      total, 39 subjects with no known history of diabetes mellitus were recruited. The
      association of 25(OH)D concentration with insulin-sensitivity was evaluated by
      hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50 nmol/l) had
      higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol
      (P = 0.012), low-density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides
      (P = 0.048), and lower insulin-sensitivity as evaluated by clamp study (P =
      0.047). There was significant correlation between 25(OH)D and BMI (r = -0.58; P =
      0.01), PTH (r = -0.44; P < 0.01), insulin-sensitivity (r = 0.43; P < 0.01), total
      (r = -0.34; P = 0.030) and LDL (r = -0.40; P = 0.023) (but not high-density
      lipoprotein (HDL)) cholesterol, and triglycerides (r = 0.45; P = 0.01).
      Multivariate analysis using 25(OH)D concentration, BMI, insulin-sensitivity, HDL
      cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the
      cofactors was performed. BMI was found to be the most powerful predictor of
      25(OH)D concentration (r = -0.52; P < 0.01), whereas insulin-sensitivity was not
      significant. Our study suggested that there is no cause-effect relationship
      between vitamin D and insulin-sensitivity. In obesity, both low 25(OH)D
      concentration and insulin-resistance appear to be dependent on the increased body
      size.

PMID- 20150903
TI  - Similarity in percent body fat between white and Vietnamese women: implication
      for a universal definition of obesity.
AB  - It has been widely assumed that for a given BMI, Asians have higher percent body
      fat (PBF) than whites, and that the BMI threshold for defining obesity in Asians
      should be lower than the threshold for whites. This study sought to test this
      assumption by comparing the PBF between US white and Vietnamese women. The study
      was designed as a comparative cross-sectional investigation. In the first study,
      210 Vietnamese women ages between 50 and 85 were randomly selected from various
      districts in Ho Chi Minh City (Vietnam). In the second study, 419 women of the
      same age range were randomly selected from the Rancho Bernardo Study (San Diego,
      CA). In both studies, lean mass (LM) and fat mass (FM) were measured by dual
      energy X-ray absorptiometry (DXA) (QDR 4500; Hologic). PBF was derived as FM over
      body weight. Compared with Vietnamese women, white women had much more FM (24.8
      +/- 8.1 kg vs. 18.8 +/- 4.9 kg; P < 0.0001) and greater PBF (36.4 +/- 6.5% vs.
      35.0 +/- 6.2%; P = 0.012). However, there was no significant difference in PBF
      between the two groups after matching for BMI (35.1 +/- 6.2% vs. 35.0 +/- 5.7%; P
      = 0.87) or for age and BMI (35.6 +/- 5.1% vs. 35.8 +/- 5.9%; P = 0.79). Using the
      criteria of BMI >or=30, 19% of US white women and 5% of Vietnamese women were
      classified as obese. Approximately 54% of US white women and 53% of Vietnamese
      women had their PBF >35% (P = 0.80). Although white women had greater BMI, body
      weight, and FM than Vietnamese women, their PBF was virtually identical. Further
      research is required to derive a more appropriate BMI threshold for defining
      obesity for Asian women.

PMID- 20150904
TI  - Bioequivalence testing of immunosuppressants: concepts and misconceptions.
AB  - Immunosuppressants are considered critical dose/narrow therapeutic index drugs
      and there is the lingering suspicion among physicians and patients that generic
      versions may differ in quality and therapeutic efficacy from the brand name drug.
      The innovator's and the generic active drug molecule are exactly the same and are
      produced following exactly the same tight rules of good manufacturing practice.
      Upon oral administration, the drug molecule separates from the formulation and
      passes the membranes of gut mucosa cells; from this point on, the formulation has
      no influence on the kinetics of a drug and its biological effects. As
      formulations may differ, bioequivalence testing in healthy volunteer studies
      establishes equal relative oral bioavailability. Due to the number of patients
      required to achieve sufficient statistical power, to test the therapeutic
      equivalence of two formulations of the same drug with the same bioavailability is
      an unrealistic goal. An often overlooked fact is that the approval by drug
      regulatory agencies of several post-approval versions of the innovators'
      immunosuppressants is based on the identical guidelines used for approval of
      generics. The FDA has issued specific guidelines describing the requirements for
      approval of generic versions of tacrolimus, sirolimus, and mycophenolic acid. The
      standard average bioequivalence approach is recommended and in the cases of
      tacrolimus and sirolimus, the effect of food should also be tested. No studies in
      the patient population are requested. Immunosuppressants are not regarded as
      drugs that require a special status to establish bioequivalence between generic
      and the innovator's versions.

PMID- 20150905
TI  - Interchangeability of ciclosporin formulations in stable adult renal transplant
      recipients: comparison of Equoral and Neoral capsules in an international,
      multicenter, randomized, open-label trial.
AB  - The cost of immunosuppression following transplantation can be reduced by using
      generic ciclosporin (for example, Equoral) rather than innovator ciclosporin
      drugs such as Neoral. Thus, this study aims to evaluate the interchangeability,
      safety, and tolerability of Equoral, a generic ciclosporin, with Neoral in stable
      adult renal transplant recipients. This was a multicenter, randomized, open
      label, parallel-group clinical trial in stable renal transplant patients,
      comparing 6 months of treatment with Equoral with the same treatment period on
      Neoral. The primary end point was the between-treatment comparison of the total
      daily ciclosporin dose at the end of the study. A total of 99 patients were
      enrolled and constituted the full analysis/safety population, and 78 patients
      forming the per-protocol population were assessed for efficacy. Equoral was found
      to be equivalent to Neoral with regard to the primary end point of daily dose at
      the end of the study. This was supported by comparable serum ciclosporin levels
      at the end of the study. There were no renal transplant rejection incidents, but
      there was one death (in the Neoral group). Drug tolerability and incidence of
      adverse events were comparable between the treatment groups. In conclusion,
      Equoral and Neoral are interchangeable in stable renal transplant patients, and
      both drugs are associated with a similar safety and tolerability profile.

PMID- 20150906
TI  - Maintenance immunosuppressive therapy and generic cyclosporine A use in adult
      renal transplantation: a single center analysis.
AB  - At present, solid organ transplantation relies on chronic immunosuppression.
      Calcineurin inhibitors (CNIs) still remain one of the most important components
      in current immunosuppressive regimens. However, life-long immunosuppression of
      transplant recipients is associated with high costs for the individual, health
      care systems, and society. Hence, there is an urgent need of generic drugs that
      have the potential to exert equivalent therapeutic efficacy at a lower cost.
      Here, we report our findings of the conversion of 59 stable long-term kidney
      graft recipients from cyclosporine A (CsA) Neoral to CsA Neoimmun/Equoral. All
      patients displayed a continuous stable graft function after conversion for a
      follow-up period of 6 months, and no major side effects associated with the use
      of CsA Neoimmun/Equoral were observed. Also, CsA dose and trough levels did not
      differ after conversion to CsA Neoimmun/Equoral. These data indicate that
      conversion of long-term kidney graft recipients from CsA Neoral to CsA
      Neoimmun/Equoral is safe and effective, making this specific CsA generic a viable
      option for CNI therapy in stable renal transplant patients.

PMID- 20150907
TI  - The efficacy of antihypertensive treatment in pregnant women with chronic and
      gestational hypertension: a population-based study.
AB  - The efficacy of antihypertensive treatment was investigated in pregnant women
      with chronic hypertension (CH) or gestational hypertension (GH) on the basis of
      the occurrence of pregnancy complications and adverse birth outcomes. Medically
      recorded pregnancy complications and birth outcomes of 1579 pregnant women with
      CH and 1098 pregnant women with GH were compared to 34,633 pregnant women without
      CH, GH, preeclampsia-eclampsia or any secondary hypertension who delivered
      newborn infants without defects in the population-based data set of the Hungarian
      Case-Control Surveillance System of Congenital Abnormalities, 1980-1996. Of 1579
      (4.1%) pregnant women with CH, 1522 (96.4%) were treated with antihypertensive
      drugs. Of 1098 (2.9%) pregnant women with GH, 657 (59.8%) were treated. Pregnant
      women with treated CH had a higher risk of threatened abortion, preterm delivery,
      and placental disorders, in addition to low-birthweight newborns. However,
      pregnant women with untreated CH and GH had no higher risk of pregnancy
      complications or adverse pregnancy outcomes. Antihypertensive treatments were not
      able to neutralize the harm of severe CH in pregnant women, the antihypertensive
      treatments were not appropriate and/or effective, or related drug treatments may
      contribute to these adverse effects.

PMID- 20150908
TI  - The second systolic radial blood pressure peak predicts cardiovascular risk only
      in subjects below 50 years of age.

PMID- 20150909
TI  - Angiotensin receptor blockers in hypertension. New insights from Japan.
AB  - Angiotensin II receptor blockers (ARBs) are widely used in the treatment of
      patients with hypertension, heart failure, diabetic nephropathy and other
      clinical conditions. Several intervention trials and systematic overviews showed
      that both angiotensin-converting enzyme inhibitors and ARBs effectively reduce
      the risk of stroke, myocardial infarction and congestive heart failure in
      hypertensive patients. Two recent intervention trials conducted in Japan (JIKEI
      and Kyoto studies) suggested that the protective effect of ARBs on major
      cardiovascular events might be partly independent from the degree of blood
      pressure (BP) reduction. Both studies used a prospective randomized open blinded
      end point (PROBE) design. No significant differences emerged in both studies
      between the ARB group (valsartan) and the control group in the achieved BP. We
      made a pooled analysis of the JIKEI and Kyoto studies. Overall, valsartan
      significantly reduced the risk of the primary composite outcome (by 42%;
      P<0.0001), angina pectoris (by 38%; P<0.0001), heart failure requiring
      hospitalization (by 43%; P=0.013) and cerebrovascular events (by 42%; P=0.002).
      The protective effect on the dissecting aneurysm of aorta bordered statistical
      significance. These data reinforce the notion that the protective effect of
      angiotensin II inhibition is partly independent of BP reduction.

PMID- 20150910
TI  - Evaluation of a new and automated electrochemiluminescence immunoassay for plasma
      sFlt-1 and PlGF levels in women with preeclampsia.
AB  - The first commercial automated immunoassays specific for soluble fms-like
      tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) (Elecsys sFlt-1 and
      Elecsys PlGF, respectively) have recently been introduced. We constructed
      reference range values of plasma levels of sFlt-1 and PlGF, and the sFlt-1/PlGF
      ratio using Elecsys sFlt-1 and Elecsys PlGF during the second half of pregnancy
      and evaluated their sensitivity and specificity for the diagnosis of
      preeclampsia. Plasma samples were collected from 144 normal pregnant women at 19
      25, 27-31 and 34-38 weeks of gestation and from 34 women with preeclampsia. The
      most appropriate reference range curves for plasma levels of sFlt-1 and PlGF, and
      the sFlt-1/PlGF ratio are presented as quadratic curves after logarithmic
      transformation. The sFlt-1/PlGF ratio showed the best diagnostic power for both
      early-onset and late-onset preeclampsia. In addition, a cutoff value of 45 for
      the sFlt-1/PlGF ratio resulted in the best sensitivity and specificity for the
      diagnosis of all preeclampsia (97 and 95%, respectively), and for the diagnosis
      of early-onset preeclampsia (100 and 95%, respectively). Using another 50 pairs
      of serum and plasma samples, including those from normal pregnant women and
      preeclamptic women, the plasma recovery rates of sFlt-1 and PlGF were 0.89 and
      0.85, respectively; the correlation determinations between serum and plasma
      samples were 0.999 for sFlt-1, 0.990 for PlGF and 0.987 for sFlt-1/PlGF ratio. In
      conclusion, measurement of the plasma sFlt-1/PlGF ratio determined by Elecsys
      sFlt-1 and Elecsys PlGF and using a cutoff value of 45 might assist in the
      diagnosis of preeclampsia, especially for early-onset preeclampsia.

PMID- 20150911
TI  - Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in
      patients with primary aldosteronism.
AB  - Adrenomedullin (AM) is located in the zona glomerulosa of the adrenal cortex and
      is considered to suppress aldosterone release. To determine the effect of AM in
      primary aldosteronism (PA), we infused AM (2.5 pmol kg(-1) min(-1)) for 27 h,
      followed by a 15-h recovery period, in a control group (essential hypertensives
      with plasma aldosterone levels <or=100 pg ml(-1), n=7) and in a PA group (n=5).
      The control group was also infused with vehicle. Hemodynamic, hormonal, oxidative
      and inflammatory responses were studied. AM infusion caused similar and steady
      decreases in blood pressure and several markers for arteriosclerosis (for
      example, pulse wave velocity) in both groups. Interestingly, AM infusion
      suppressed aldosterone release to values within the normal range in the PA group
      (300.0+/-58.4 to 111.6+/-13.5 pg ml(-1), P<0.01). In the control group,
      aldosterone release suppression was significant but limited (81.7+/-9.1 to 47.9+/
      9.9 pg ml(-1), P<0.01). The adrenocorticotropic hormone-cortisol system was not
      changed by AM infusion. Brain natriuretic peptide was cumulatively increased by
      prolonged AM infusion in both groups, probably because of cardiac overload. AM
      did not affect oxidative markers. In addition, a mild but significant increase in
      C-reactive protein (CRP) mediated by interleukin-6 was observed during AM
      infusion in every participant, without exception. This pathway might participate
      in CRP elevation in cardiovascular disease. In summary, AM seems to have an
      essential role in the suppression of aldosterone release in PA. AM may be an
      important modulator in PA, and intermediate-term (3 h) AM infusion could be used
      as an alternative renin-stimulating/aldosterone-suppressing test for PA
      detection.

PMID- 20150912
TI  - Prostaglandin (PG)D(2) and 15-deoxy-Delta(12,14)-PGJ(2), but not PGE(2), mediate
      shear-induced chondrocyte apoptosis via protein kinase A-dependent regulation of
      polo-like kinases.
AB  - Excessive mechanical loading of cartilage producing hydrostatic stress, tensile
      strain and fluid flow leads to chondrocyte apoptosis and osteoarthritis. High
      fluid flow induces cyclooxygenase-2 (COX-2) expression in sheared chondrocytes,
      which suppresses their antioxidant capacity and contributes to apoptosis. The
      pivotal role of COX-2 in shear-induced chondrocyte apoptosis and the conflicting
      literature data on the roles of prostaglandin (PG)E(2), PGD(2) and its metabolite
      15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) in chondrocyte apoptosis prompted us to
      analyze which COX-2-derived PG is involved in this process. We show that
      exogenously added PGD(2) and 15d-PGJ(2), but not PGE(2), diminish the viability
      of human T/C-28a2 chondrocytes under static conditions. In agreement with these
      observations, knockdown of L-PGD synthase (L-PGDS) abolishes shear-induced
      chondrocyte apoptosis. Using cDNA microarrays in conjunction with clustering
      algorithms, we propose a novel signaling pathway by which high fluid shear
      mediates COX-2/L-PGDS-dependent chondrocyte apoptosis, which is validated by
      molecular interventions. We show that L-PGDS controls the downregulation of
      protein kinase A (PKA), which in turn regulates Polo-like kinase1 (Plk1) and
      Plk3. Plks target p53, which controls the transcription of p53 effectors
      (TP53INPs, FAS and Bax) involved in chondrocyte apoptosis. Reconstructing the
      signaling network regulating chondrocyte apoptosis may provide insights to
      optimize conditions for culturing artificial cartilage in bioreactors and for
      developing therapeutic strategies for arthritic disorders.

PMID- 20150913
TI  - c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein
      Galectin-3.
AB  - Galectin-3 (Gal3) has important roles in tumor transformation and metastasis.
      This study shows that c-Abl and Abl-related gene (Arg) associate with and
      phosphorylate Gal3. The SH (Src homology)3 domains of c-Abl/Arg bind to a
      P(80)GPPSGP motif of Gal3, and Tyr79 and Tyr118 are the major tyrosine
      phosphorylation sites. A consequence of this interaction and phosphorylation is
      the significant impairment of chaperone-mediated autophagy of Gal3. Cells
      expressing Gal3 and treated with the c-Abl/Arg inhibitor STI571, Gal3-depleted
      cells, and Gal3-depleted cells expressing Gal3 phosphorylation mutants all
      display an increased sensitivity to apoptosis-inducing agents. In addition, tumor
      cells expressing the phosphorylation mutants show impaired tumorigenicity. These
      results partially explain the antiapoptotic effect of Abl and Arg. As tumors
      frequently overexpress Gal3, a c-Abl/Arg-specific inhibitor may potentially be
      applied along with other antitumor drugs to target the lysosomal degradation of
      Gal3 in tumor therapy.

PMID- 20150914
TI  - Fas ligand gene expression is directly regulated by stress-inducible heat shock
      transcription factor-1.
AB  - Heat shock transcription factor-1 (HSF-1) is the primary stress responsive
      transcription factor that regulates expression of heat shock proteins (Hsps) in
      response to elevated temperature. We show that the transcriptional activity of
      HSF-1 can also directly mediate hyperthermia-induced Fas ligand (FasL) expression
      in activated T cells. We identify a conserved region within the human FasL
      promoter spanning from -276 to -236 upstream of the translational start site that
      contains two 15 bp non-identical adjacent HSF-1-binding sites or heat shock
      elements (HSEs) separated by 11 bp. Both the distal HSE (HSE1) (extending from 
      276 to -262) and the proximal HSE (HSE2) (spanning from -250 to -236) consist of
      two perfect and one imperfect nGAAn pentamers. We show the direct binding of HSF
      1 to these elements and that mutation of these sites abrogates the ability of HSF
      1 to bind and drive promoter activity. HSF-1 associates with these elements in a
      cooperative manner to mediate optimal promoter activity. We propose that the
      ability of HSF-1 to mediate stress-inducible expression of FasL extends its
      classical function as a regulator of Hsps to encompass a function for this
      transcription factor in the regulation of immune function and homeostasis.

PMID- 20150915
TI  - An essential function for the centrosomal protein NEDD1 in zebrafish development.
AB  - The centrosome is the primary microtubule organising centre of the cell. It is
      composed of many proteins, some of which make up the core of the centrosome,
      whereas others are used for specific functions. Although the cellular roles of
      many centrosomal proteins are well defined, much less is known about their
      functions and the role of the centrosome in development. In this study we
      investigated the function of NEDD1, a critical component of the centrosome
      essential for microtubule nucleation, in zebrafish (Danio rerio) development. The
      zebrafish homologue of NEDD1 (zNEDD1) was cloned and found to have a similar
      localisation and function to mammalian NEDD1. We show that zNEDD1 is essential
      for survival, as a high level of knockdown was embryonic lethal. Partial
      knockdown of zNEDD1 caused abnormalities including an increase in mitotic and
      apoptotic cells. Pronounced phenotypic defects were seen in the brain, with a
      lack of defined brain structures, incomplete neural tube formation and a
      disorganisation of neurons. In addition, we show that a reduction in zNEDD1
      resulted in the loss of gamma-tubulin at the centrosome. Our data thus
      demonstrate that zNEDD1 is critical for the recruitment of gamma-tubulin to the
      centrosome, and is essential for the proper development of zebrafish.

PMID- 20150916
TI  - A systems level strategy for analyzing the cell death network: implication in
      exploring the apoptosis/autophagy connection.
AB  - The mammalian cell death network comprises three distinct functional modules:
      apoptosis, autophagy and programmed necrosis. Currently, the field lacks systems
      level approaches to assess the extent to which the intermodular connectivity
      affects cell death performance. Here, we developed a platform that is based on
      single and double sets of RNAi-mediated perturbations targeting combinations of
      apoptotic and autophagic genes. The outcome of perturbations is measured both at
      the level of the overall cell death responses, using an unbiased quantitative
      reporter, and by assessing the molecular responses within the different
      functional modules. Epistatic analyses determine whether seemingly unrelated
      pairs of proteins are genetically linked. The initial running of this platform in
      etoposide-treated cells, using a few single and double perturbations, identified
      several levels of connectivity between apoptosis and autophagy. The knock down of
      caspase3 turned on a switch toward autophagic cell death, which requires Atg5 or
      Beclin-1. In addition, a reciprocal connection between these two autophagic genes
      and apoptosis was identified. By applying computational tools that are based on
      mining the protein-protein interaction database, a novel biochemical pathway
      connecting between Atg5 and caspase3 is suggested. Scaling up this platform into
      hundreds of perturbations potentially has a wide, general scope of applicability,
      and will provide the basis for future modeling of the cell death network.

PMID- 20150920
TI  - A functional polymorphism (-603A --> G) in the tissue factor gene promoter is
      associated with adult-onset asthma.
AB  - Tissue factor (TF) is important for initiation of coagulation and for the
      increased thrombin activity observed at sites of inflammation. Thrombin activity
      is induced by allergen challenge in asthmatic airways and is involved in the
      pathogenesis of asthma. A -603A --> G polymorphism (rs1361600) in the promoter
      region of the TF gene has been associated with serum TF levels and with the
      development of cardiovascular diseases. The aim of this study was to determine
      whether the functional -603A --> G polymorphism has genetic influences on the
      development of asthma. Case-control analysis was performed of the association
      between six common single-nucleotide polymorphisms (SNPs), including the -603A -
      > G polymorphism, at the TF gene, and the development of asthma, using two
      unrelated Japanese populations. In the primary population (n=826), the GG
      genotype at the -603A --> G polymorphism was associated with adult-onset asthma
      (onset at >or=21 years of age) (odds ratio (OR) 2.886, P=0.0231). A second
      population showed a similar tendency (n=1654, OR 1.602, P=0.064). Transcriptional
      activity of promoters with -603A --> G genotypes were examined using luciferase
      promoter assays. The -603G allele was associated with higher promoter activity
      (P<0.05). The association between the functional polymorphism (-603A --> G) in
      the TF gene promoter and adult-onset asthma indicates that TF is a candidate gene
      contributing to asthma susceptibility.

PMID- 20150921
TI  - Use of heavy Trypan blue in macular hole surgery.
AB  - PURPOSE: Intraocular dyes facilitate the identification of the inner limiting
      membrane (ILM) during surgery. Appropriate dyes should be safe, provide adequate
      staining, and be easy to use. Heavy Trypan blue eliminates the need for an air
      fluid exchange (AFX) and appears to have little retinal toxicity. This study
      refers to a prospective, consecutive trial with heavy Trypan blue in macular hole
      surgery. PATIENTS AND METHODS: A consecutive group of 20 patients with full
      thickness macular holes was recruited in a single institution study. Patients
      were operated using conventional methods. Heavy Trypan blue was prepared by
      mixing isovolumetrically glucose 10% with MembraneBlue (DORC, Zuidland, The
      Netherlands). Patients were assessed for ease of surgery and post-operatively at
      3 and 6 months (vision and ocular coherence tomography) for hole closure and
      vision. RESULTS: Twenty eyes were included in the study. Reapplication of dye was
      used in 75% of the cases, leading to improved contrast further facilitating the
      ILM peel. In no case was an AFX necessary to obtain sufficient staining. Macular
      hole closure was achieved in 19 of 20 patients with one surgery. No retinal
      detachment or other complication was observed in the follow-up period.
      CONCLUSION: Heavy Trypan blue can be delivered efficiently to the retinal surface
      without the need for an AFX. Staining was sufficient to help visualise and peel
      the ILM. Repeat applications were easily performed. The macular hole closure rate
      was similar to that of other series with a comparable visual improvement.

PMID- 20150917
TI  - Transcriptional upregulation of both egl-1 BH3-only and ced-3 caspase is required
      for the death of the male-specific CEM neurons.
AB  - Most of the 131 cells that die during the development of a Caenorhabditis elegans
      hermaphrodite do so approximately 30 min after being generated. Furthermore, in
      these cells, the pro-caspase proCED-3 is inherited from progenitors and the
      transcriptional upregulation of the BH3-only gene egl-1 is thought to be
      sufficient for apoptosis induction. In contrast, the four CEM neurons, which die
      in hermaphrodites, but not males, die approximately 150 min after being
      generated. We found that in the CEMs, the transcriptional activation of both the
      egl-1 and ced-3 gene is necessary for apoptosis induction. In addition, we show
      that the Bar homeodomain transcription factor CEH-30 represses egl-1 and ced-3
      transcription in the CEMs, thereby permitting their survival. Furthermore, we
      identified three genes, unc-86, lrs-1, and unc-132, which encode a POU
      homeodomain transcription factor, a leucyl-tRNA synthetase, and a novel protein
      with limited sequence similarity to the mammalian proto-oncoprotein and kinase
      PIM-1, respectively, that promote the expression of the ceh-30 gene in the CEMs.
      On the basis of these results, we propose that egl-1 and ced-3 transcription are
      coregulated in the CEMs to compensate for limiting proCED-3 levels, which most
      probably are a result of proCED-3 turn over. Similar coregulatory mechanisms for
      BH3-only proteins and pro-caspases may function in higher organisms to allow
      efficient apoptosis induction. Finally, we present evidence that the timing of
      the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator
      of somatic sexual fate in C. elegans.

PMID- 20150922
TI  - Circulating markers of arterial thrombosis and late-stage age-related macular
      degeneration: a case-control study.
AB  - PURPOSE: The aim of this study was to examine the relation of late-stage age
      related macular degeneration (AMD) with markers of systemic atherothrombosis.
      METHODS: A hospital-based case-control study of AMD was undertaken in London, UK.
      Cases of AMD (n=81) and controls (n=77) were group matched for age and sex.
      Standard protocols were used for colour fundus photography and to classify AMD;
      physical examination included height, weight, history of or treatment for
      vascular-related diseases and smoking status. Blood samples were taken for
      measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin
      fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor.
      Odds ratios from logistic regression analyses of each atherothrombotic marker
      with AMD were adjusted for age, sex, and established cardiovascular disease risk
      factors, including smoking, blood pressure, body mass index, and total
      cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely
      associated with the risk of AMD; per 1 standard deviation increase in these
      markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40,
      0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors
      appeared to be related to AMD status. There was weak evidence that aspirin is
      associated with a lower risk of AMD. CONCLUSIONS: This study does not provide
      strong evidence of associations between AMD and systematic markers of arterial
      thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further
      investigation.

PMID- 20150923
TI  - Comparison of three methods of intraocular pressure measurement and their
      relation to central corneal thickness.
AB  - PURPOSE: The purpose of this study was to compare the reliability of the 'gold
      standard' Goldmann applanation tonometer (GAT), with that of the ocular response
      analyser (ORA), and the dynamic contour tonometer (DCT). PATIENTS AND METHODS: A
      total of 694 subjects were recruited to participate from the TwinsUK (UK Adult
      Twin Registry) at St Thomas' Hospital, London. Intraocular pressure (IOP) was
      measured using GAT, ORA, and the DCT. The agreement between the three methods was
      assessed using the Bland-Altman method. Repeatability coefficients and
      coefficient of variation between first and second readings of the same eye were
      used to assess reliability. RESULTS: Mean age was 57.5 years (SD, 13.1; range,
      16.1-88.5). The mean IOPs, calculated using the mean of two readings from the
      right eye were as follows: Goldmann (GAT), 14.1+/-2.8 mm Hg; IOPg (ORA), 15.9+/
      3.2 mm Hg; IOPcc (ORA), 16.6+/-3.2 mm Hg; and DCT, 16.9+/-2.7 mm Hg. The 95%
      limits of agreement were for ORA (IOPcc): GAT, -2.07 to 7.18 mm Hg; for DCT: GAT,
      -0.49 to 6.21 mm Hg; and for DCT: ORA (IOPcc), -3.01 to 4.85 mm Hg. Coefficients
      of variation for the three tonometers were GAT, 8.3%; ORA, 8.2%; DCT, 6.3%. The
      repeatability coefficients were 3.4 mm Hg for GAT, 3.57 mm Hg for ORA and 3.09 mm
      Hg for DCT. GAT and ORA (IOPg) readings showed a positive correlation with
      central corneal thickness (P<0.005). CONCLUSIONS: This study found similar
      reliability in all three tonometers. Bland-Altman plots showed the three
      instruments to have 95% limits of agreement outside the generally accepted
      limits, which means they are not interchangeable. GAT measurements were found to
      be significantly lower than the two newer instruments.

PMID- 20150924
TI  - The natural history of the Charles Bonnet Syndrome. Do the hallucinations go
      away?

PMID- 20150925
TI  - Tear proteomics in evaporative dry eye disease.
AB  - PURPOSE: To analyze tear protein variations in patients suffering from dry eye
      symptoms in the presence of tear film instability but without epithelial defects.
      METHODS: Five microlitres of non-stimulated tears from 60 patients, suffering
      from evaporative dry eye (EDE) with a break-up time (BUT) <10 s, and from 30
      healthy subjects as control (no symptoms, BUT >10 s) were collected. Tear
      proteins were separated by mono and bi-dimensional SDS-PAGE electrophoresis and
      characterized by immunoblotting and enzymatic digestion. Digested peptides were
      analyzed by liquid chromatography coupled to electrospray ionization quadrupole
      time of flight mass spectrometry followed by comparative data analysis into Swiss
      Prot human protein database using Mascot. Statistical analysis were performed by
      applying a t-test for independent data and a Mann-Whitney test for unpaired data
      (P<0.05). RESULTS: In EDE patients vscontrols, a significant decrease in levels
      of lactoferrin (data in %+/-SD): 20.15+/-2.64 vs 24.56+/-3.46 (P=0.001),
      lipocalin-1: 14.98+/-2.70 vs 17.73+/-2.96 (P=0.0001), and lipophilin A-C: 2.89+/
      1.06 vs 3.63+/-1.37 (P=0.006) was revealed, while a significant increase was
      observed for serum albumin: 9.45+/-1.87 vs 3.46+/-1.87 (P=0.0001). No changes for
      lysozyme and zinc alpha-2 glycoprotein (P=0.07 and 0.7, respectively) were shown.
      Proteomic analysis showed a downregulation of lipophilin A and C and lipocalin-1
      in patients, which is suggested to be associated with post-translational
      modifications. CONCLUSIONS: Data show that tear protein changes anticipate the
      onset of more extensive clinical signs in early stage dry eye disease.

PMID- 20150926
TI  - Glued posterior chamber IOL in eyes with deficient capsular support: a
      retrospective analysis of 1-year post-operative outcomes.
AB  - PURPOSE: To evaluate the post-operative outcome of fibrin glue-assisted posterior
      chamber intraocular lens (IOL) implantation in eyes with deficient capsular
      support after 1 year. METHODS: Eyes operated with fibrin glue-assisted posterior
      chamber IOL implantation from December 2007 to May 2008 were included. The post
      operative best spectacle-corrected visual acuity (BCVA), uncorrected visual
      acuity (UCVA), intraocular pressure (IOP), central macular thickness, and
      specular count were evaluated. IOL position and centration at 1 year was
      determined. The 1-year post-operative complications were analysed. RESULTS: A
      total of 53 eyes of 53 patients were analysed. There was significant improvement
      in UCVA (P=0.000) and BCVA (P=0.000). There was no significant change (P=0.447)
      in IOP from the pre-operative value. The early post-operative complication was
      decentration (5.6%). The late complication was pigment dispersion (3.7%) and
      healed macular oedema (7.5%). No vision threatening complications such as retinal
      break, retinal detachment, or endophthalmitis were seen. The percentage (%) loss
      of endothelial cells was 5.23+/-3.4% at 1-year follow-up. No pseudophakodonesis
      was seen in the follow-up visits. CONCLUSION: Results obtained at 1 year after
      fibrin glue-assisted posterior chamber IOL implantation showed a good visual
      outcome with minimal complications in eyes with deficient capsular support.

PMID- 20150927
TI  - Ranibizumab for retinal angiomatous proliferation in age-related macular
      degeneration.
AB  - PURPOSE: To assess the 1-year functional outcome and to evaluate the
      morphological changes after intravitreal injections of ranibizumab in eyes
      affected with retinal angiomatous proliferation (RAP) due to age-related macular
      degeneration (AMD). METHODS: A prospective, non-randomized, interventional study
      was conducted on 26 consecutive patients with newly diagnosed RAP. All eyes were
      treatment naive and were randomized to receive intravitreal injections of
      ranibizumab for a 12-month period. After the first three monthly injections, re
      treatment was performed in case of best-corrected visual acuity (BCVA) loss of at
      least five letters associated with fluid within the macula, central macular
      thickness (CMT) increase of at least 100 microm, and/or persistence of fluid
      within the macula as evaluated by optical coherence tomography, new onset macular
      haemorrhages, persistence of leakage from the lesions on fluorescein angiography.
      RESULTS: All patients completed the 12-month follow-up: 25 of the 29 treated eyes
      (86.2%) were stabilized, with a loss of less than 15 letters. Nineteen eyes
      (65.5%) maintained or improved their BCVA, and three eyes (10.3%) gained three
      lines or more. Overall, mean BCVA remained stable at the 12-month follow-up (
      0.07 letters; P>0.05). Mean CMT significantly decreased from 386+/-147 to 216+/
      74 microm at the 12-month follow-up. No significant adverse events were observed
      during the study. The mean number of injections was 5.8+/-1.7 during the follow
      up period. CONCLUSION: The 1-year follow-up outcomes in our series suggest that
      ranibizumab is an effective treatment for RAP in AMD, allowing stabilization of
      BCVA and reduction of CMT.

PMID- 20150928
TI  - The spinosyn family of insecticides: realizing the potential of natural products
      research.
AB  - The spinosyns are a large family of unprecedented compounds produced from
      fermentation of two species of Saccharopolyspora. Their core structure is a
      polyketide-derived tetracyclic macrolide appended with two saccharides. They show
      potent insecticidal activities against many commercially significant species that
      cause extensive damage to crops and other plants. They also show activity against
      important external parasites of livestock, companion animals and humans. Spinosad
      is a defined combination of the two principal fermentation factors, spinosyns A
      and D. Structure-activity relationships (SARs) have been extensively studied,
      leading to development of a semisynthetic second-generation derivative,
      spinetoram. The spinosyns have a unique mechanism of action (MOA) involving
      disruption of nicotinic acetylcholine receptors. When compared with many other
      insecticides, the spinosyns generally show greater selectivity toward target
      insects and lesser activity against many beneficial predators as well as mammals
      and other aquatic and avian animals. Their insecticidal spectrum, unique MOA and
      lower environmental effect make them useful new agents for modern integrated pest
      management programs. As a result, this work has received U S Presidential Green
      Chemistry Challenge Awards.

PMID- 20150929
TI  - Antibacterial and antilarval compounds from marine gorgonian-associated bacterium
      Bacillus amyloliquefaciens SCSIO 00856.

PMID- 20150930
TI  - Cytokine-armed vaccinia virus infects the mesothelioma tumor microenvironment to
      overcome immune tolerance and mediate tumor resolution.
AB  - Intratumoral (i.t.) administration of cytokine genes expressed by viral vectors
      represents a rational approach that induces cytokine secretion at the site they
      are needed, and i.t. vaccinia virus (VV) has shown promise in mesothelioma
      patients. However, we and others have shown that the mesothelioma tumor
      microenvironment includes macrophages, dendritic cells (DCs), and T cells.
      Therefore, we investigated which of these cell types are infected after exposure
      to VV or Fowlpox virus (FPV)-cytokine gene constructs. In vitro studies showed
      that mesothelioma tumor cells were resistant to FPV infection yet highly
      permissive to infection by VV vectors resulting in significant cytokine
      production and impaired proliferation. Macrophages secreted low levels of
      cytokine suggestive of resistance to overt infection. DCs transiently secreted
      virally derived cytokines, but did not mature during VV infection. VV inhibition
      of T cell proliferation was rescued by the interleukin (IL)-2 and IL-12 VV
      constructs. In vivo studies of murine mesotheliomas showed that i.t. injection of
      the parent VV could not hinder tumor progression. In contrast, the VV-cytokine
      constructs induced profound tumor regression. These data suggest that i.t. VV
      cytokine gene constructs retard tumor growth by infecting mesothelioma cells and
      targeting the immune system through tumor-infiltrating DC and T cells.

PMID- 20150931
TI  - Bleomycin/interleukin-12 electrochemogene therapy for treating naturally
      occurring spontaneous neoplasms in dogs.
AB  - On the basis of superior outcomes from electrochemogene therapy (ECGT) compared
      with electrochemotherapy in mice, we determined the efficacy of ECGT applied to
      spontaneous canine neoplasms. Intralesional bleomycin and feline interleukin-12
      DNA (fIL-12 DNA) injection combined with translesional electroporation resulted
      in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0)
      oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous
      ameloblastoma. Three remaining dogs, which had no other treatment options, had
      partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with
      pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic
      sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0)
      fibrosarcoma. The melanoma dog had decrease in size of the primary tumor before
      recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the
      primary tumor, but was euthanized because of metastases 4 months after the only
      treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with
      recrudescence. Treatment was associated with minimal side effects and was easy to
      perform. It was associated with repair of bone lysis in cured dogs, it improved
      quality of life of dogs with partial responses and extended overall survival
      time. ECGT seems to be a safe and resulted in complete responses in SCC and
      acanthomatous ameloblastoma.

PMID- 20150932
TI  - Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3)
      improves therapeutic efficacy in low CAR prostate cancer cells.
AB  - Gene therapy is being examined as a potential strategy for treating prostate
      cancer. Serotype 5 adenovirus (Ad.5) is routinely used as a vector for transgene
      delivery. However, the infectivity of Ad.5 is dependent on Coxsackie-adenovirus
      receptors (CARs); many tumor types show a reduction in this receptor in vivo,
      thereby limiting therapeutic gene transduction. Serotype chimerism is one
      approach to circumvent CAR deficiency; this strategy is used to generate an
      Ad.5/3-recombinant Ad that infects cancer cells through Ad.3 receptors in a CAR
      independent manner. In this report, the enhanced transgene delivery and efficacy
      of Ad.5/3-recombinant virus was evaluated using an effective wide-spectrum
      anticancer therapeutic melanoma differentiation-associated gene-7/interleukin-24
      (mda-7/IL-24). Our data show that in low CAR human prostate cancer cells (PC-3),
      a recombinant Ad.5/3 virus delivering mda-7/IL-24 (Ad.5/3-mda-7) is more
      efficacious than an Ad.5 virus encoding mda-7/IL-24 (Ad.5-mda-7) in infecting
      tumor cells, expressing MDA-7/IL-24 protein, inducing cancer-specific apoptosis,
      inhibiting in vivo tumor growth and exerting an antitumor 'bystander' effect in a
      nude mouse xenograft model. Considering the fact that Ad.5-mda-7 has shown
      significant objective responses in a phase I clinical trial for solid tumors,
      Ad.5/3-mda-7 is predicted to exert enhanced therapeutic benefit in patients with
      prostate cancer.

PMID- 20150934
TI  - Diabetic kidney disease: act now or pay later.

PMID- 20150935
TI  - Deceased-donor renal transplantation program in India.

PMID- 20150937
TI  - Evidence of true genotype-phenotype correlation in primary hyperoxaluria type 1.
AB  - A genotype-phenotype correlation in patients with primary hyperoxaluria type 1
      and specific AGXT mutations has supposedly been found, at least for sensitivity
      to medication and long-term outcome. Nevertheless, other determinants, such as
      environmental factors or modifier genes, must play an essential role in the intra
      and interfamilial heterogeneity of this disease. Harambat and co-workers report
      on this situation, presenting data on a major population of genotyped patients.

PMID- 20150938
TI  - A powerful new agonist: flooding the system with growth hormone.
AB  - Niemczyk et al. treated predialysis chronic kidney disease patients with a new
      growth hormone-releasing hormone agonist, AKL-0707, and noted important changes
      in body composition characterized by an increase in fat-free mass, a modest rise
      in bone mineral content, and a reduction in fat mass. These changes were
      accompanied by a reduction in both serum urea nitrogen and normalized protein
      nitrogen appearance rate, while dietary protein intake was unchanged.
      Importantly, there were no serious adverse events.

PMID- 20150939
TI  - ROCK inhibition facilitates tissue reconstitution from embryonic kidney cell
      suspensions.
AB  - Explanted embryonic kidney tissues, when placed in organ culture, recapitulate
      key aspects of nephron formation. Yet attempts to dissociate these tissues into
      single cells to make them more accessible for genetic manipulation and tissue
      recombination have been disappointing. Now it is reported that inhibitors of Rho
      associated kinase (ROCK) facilitate tissue reconstitution and nephron
      differentiation from single-cell suspensions of the embryonic kidney. This
      finding illustrates an unexpected potential for self-organization in these cells
      and introduces a window of single-cell accessibility to the organ culture system.

PMID- 20150940
TI  - Does the downregulation of the FGF23 signaling pathway in hyperplastic
      parathyroid glands contribute to refractory secondary hyperparathyroidism in CKD
      patients?
AB  - Compared to normal tissue, hyperplastic parathyroid glands of patients with
      chronic kidney disease on dialysis express lower levels of FGFR1 and Klotho
      proteins. Similar findings are reported in uremic rats with advanced chronic
      kidney disease. Moreover, in these animals, FGF23 administration fails to reduce
      PTH serum levels in vivo and to transmit downstream signals in parathyroid cells
      ex vivo. These findings may explain, at least partly, the concomitant elevation
      of both FGF23 and PTH serum levels in chronic kidney disease secondary
      hyperparathyroidism.

PMID- 20150942
TI  - Antineutrophil cytoplasmic autoantibody-associated vasculitis on chronic
      dialysis.

PMID- 20150943
TI  - Thyrotoxicosis factitia induces Takotsubo cardiomyopathy in end-stage renal
      disease: a pathogenetic hypothesis.

PMID- 20150944
TI  - CRRT in series with extracorporeal membrane oxygenation in pediatric patients.

PMID- 20150946
TI  - Nephroprotective drugs from traditionally used Aboriginal medicinal plants.

PMID- 20150948
TI  - Anti-phospholipid antibody syndrome in the kidney.

PMID- 20150949
TI  - The case: 41-year-old HIV patient with proteinuria and progressive renal
      dysfunction. Tenofovir toxicity.

PMID- 20150950
TI  - Cryptococcus gattii outbreak expands into the Northwestern United States with
      fatal consequences.
AB  - In the past decade, the primary fungal pathogen Cryptococcus gattii has evolved
      and adapted to the temperate climate of the Pacific Northwest region of North
      America. This pathogen is now endemic and an increasingly common cause of life
      threatening pulmonary and central nervous system infections that are difficult to
      manage and, in some cases, fatal to humans and other mammals throughout the
      region. A series of recent reports provide evidence that evolutionary, climatic,
      and anthropogenic factors may be causing the expansion of the Vancouver Island
      outbreak genotype into the United States, with the concomitant emergence of a
      unique genotype in the state of Oregon. Ongoing studies address the molecular
      epidemiology, roles of mating and genetic exchange, and geographic origins of
      this unprecedented outbreak of fungal infection of considerable public health
      magnitude.

PMID- 20150951
TI  - Contextualizing CBPR: Key Principles of CBPR meet the Indigenous research
      context.
AB  - This paper addresses two questions regarding the use of Community-based
      Participatory Research (CBPR) approaches with tribal communities. First, how do
      "gold standard" CBPR principles hold up when applied to Native American
      communities and what additional contextual information is necessary to understand
      and work with these principles in this setting? Second, what additional
      principles or recommendations are helpful for researchers interested in
      conducting research using a CBPR approach with tribal communities? We studied a
      variety of literature sources on CBPR and Native health research to answer these
      questions. We are unaware of any publications that contextualize CBPR principles
      for working with specific populations. This information has direct application
      for conducting research with tribal communities, and confirms the importance of
      using CBPR approaches in this setting.

PMID- 20150952
TI  - Coupling the Level-Set Method with Molecular Mechanics for Variational Implicit
      Solvation of Nonpolar Molecules.
AB  - We construct a variational explicit-solute implicit-solvent model for the
      solvation of molecules. Central in this model is an effective solvation free
      energy functional that depends solely on the position of solute-solvent interface
      and solute atoms. The total free energy couples altogether the volume and
      interface energies of solutes, the solute-solvent van der Waals interactions, and
      the solute-solute mechanical interactions. A curvature dependent surface tension
      is incorporated through the so-called Tolman length which serves as the only
      fitting parameter in the model. Our approach extends the original variational
      implicit-solvent model of Dzubiella, Swanson, and McCammon [Phys. Rev. Lett.
      2006, 96, 087802 and J. Chem. Phys. 2006, 124, 084905] to include the solute
      molecular mechanics. We also develop a novel computational method that combines
      the level-set technique with optimization algorithms to determine numerically the
      equilibrium conformation of nonpolar molecules. Numerical results demonstrate
      that our new model and methods can capture essential properties of nonpolar
      molecules and their interactions with the solvent. In particular, with a suitable
      choice of the Tolman length for the curvature correction to the surface tension,
      we obtain the solvation free energy for a benzene molecule in a good agreement
      with experimental results.

PMID- 20150953
TI  - Small molecule hydration free energies in explicit solvent: An extensive test of
      fixed-charge atomistic simulations.
AB  - Using molecular dynamics free energy simulations with TIP3P explicit solvent, we
      compute the hydration free energies of 504 neutral small organic molecules and
      compare them to experiments. We find, first, good general agreement between the
      simulations and the experiments, with an RMS error of 1.24 kcal/mol over the
      whole set (i.e., about 2 kT) and a correlation coefficient of 0.89. Second, we
      use an automated procedure to identify systematic errors for some classes of
      compounds, and suggest some improvements to the force field. We find that alkyne
      hydration free energies are particularly poorly predicted due to problems with a
      Lennard-Jones well depth, and find that an alternate choice for this well depth
      largely rectifies the situation. Third, we study the non-polar component of
      hydration free energies - that is, the part that is not due to electrostatics.
      While we find that repulsive and attractive components of the non-polar part both
      scale roughly with surface area (or volume) of the solute, the total non-polar
      free energy does not scale with the solute surface area or volume, because it is
      a small difference between large components and is dominated by the deviations
      from the trend. While the methods used here are not new, this is a more extensive
      test than previous explicit solvent studies, and the size of the test set allows
      identification of systematic problems with force field parameters for particular
      classes of compounds. We believe that the computed free energies and components
      will be valuable to others in future development of force fields and solvation
      models.

PMID- 20150954
TI  - The decreased growth hormone response to growth hormone releasing hormone in
      obesity is associated to cardiometabolic risk factors.
AB  - The aim of the present study was to evaluate the relationship between GHRH
      induced GH secretion in obese premenopausal women and cardiovascular risk markers
      or insulin resistance. Premenopausal obese women, aged 35-52 years, were studied.
      GH secretion, IGF-I, serum cardiovascular risk markers, insulin, leptin, mid
      waist and hip circumference, total body fat, and truncal fat were measured.
      Subjects were classified as meeting the criteria for GH deficiency (GHD) when
      peak GH after stimulation with GHRH was <or=3 microg/L. Mean total and LDL
      cholesterol, fasting insulin, and HOMA-IR were all higher, in subjects who would
      have been classified as GH-deficient compared with GH-sufficient. Peak GH
      secretion after stimulation was inversely associated with fasting insulin (R = 
      0.650, P = .012), HOMA-IR (R = -0.846, P = .001), total cholesterol (R = -0.532,
      P = .034), and LDL cholesterol (R = -0.692, P = .006) and positively associated
      with HDL cholesterol (R = 0.561, P = .037). These data strongly suggest a role
      for insulin resistance in the decreased GH secretion of obesity and that the
      blunted GH secretion of central obesity could be the pituitary expression of the
      metabolic syndrome.

PMID- 20150955
TI  - Application of symmetry adapted function method for three-dimensional
      reconstruction of octahedral biological macromolecules.
AB  - A method for three-dimensional (3D) reconstruction of macromolecule assembles,
      that is, octahedral symmetrical adapted functions (OSAFs) method, was introduced
      in this paper and a series of formulations for reconstruction by OSAF method were
      derived. To verify the feasibility and advantages of the method, two octahedral
      symmetrical macromolecules, that is, heat shock protein Degp(24) and the Red-cell
      L Ferritin, were utilized as examples to implement reconstruction by the OSAF
      method. The schedule for simulation was designed as follows: 2000 random
      orientated projections of single particles with predefined Euler angles and
      centers of origins were generated, then different levels of noises that is signal
      to-noise ratio (S/N) = 0.1, 0.5, and 0.8 were added. The structures reconstructed
      by the OSAF method were in good agreement with the standard models and the
      relative errors of the structures reconstructed by the OSAF method to standard
      structures were very little even for high level noise. The facts mentioned above
      account for that the OSAF method is feasible and efficient approach to
      reconstruct structures of macromolecules and have ability to suppress the
      influence of noise.

PMID- 20150956
TI  - Synonymous codon usage analysis of thirty two mycobacteriophage genomes.
AB  - Synonymous codon usage of protein coding genes of thirty two completely sequenced
      mycobacteriophage genomes was studied using multivariate statistical analysis.
      One of the major factors influencing codon usage is identified to be
      compositional bias. Codons ending with either C or G are preferred in highly
      expressed genes among which C ending codons are highly preferred over G ending
      codons. A strong negative correlation between effective number of codons (Nc) and
      GC3s content was also observed, showing that the codon usage was effected by gene
      nucleotide composition. Translational selection is also identified to play a role
      in shaping the codon usage operative at the level of translational accuracy. High
      level of heterogeneity is seen among and between the genomes. Length of genes is
      also identified to influence the codon usage in 11 out of 32 phage genomes.
      Mycobacteriophage Cooper is identified to be the highly biased genome with better
      translation efficiency comparing well with the host specific tRNA genes.

PMID- 20150957
TI  - Algorithmic assessment of vaccine-induced selective pressure and its implications
      on future vaccine candidates.
AB  - Posttrial assessment of a vaccine's selective pressure on infecting strains may
      be realized through a bioinformatic tool such as parsimony phylogenetic analysis.
      Following a failed gonococcal pilus vaccine trial of Neisseria gonorrhoeae, we
      conducted a phylogenetic analysis of pilin DNA and predicted peptide sequences
      from clinical isolates to assess the extent of the vaccine's effect on the type
      of field strains that the volunteers contracted. Amplified pilin DNA sequences
      from infected vaccinees, placebo recipients, and vaccine specimens were
      phylogenetically analyzed. Cladograms show that the vaccine peptides have
      diverged substantially from their paternal isolate by clustering distantly from
      each other. Pilin genes of the field clinical isolates were heterogeneous, and
      their peptides produced clades comprised of vaccinated and placebo recipients'
      strains indicating that the pilus vaccine did not exert any significant selective
      pressure on gonorrhea field strains. Furthermore, sequences of the semivariable
      and hypervariable regions pointed out heterotachous rates of mutation and
      substitution.

PMID- 20150958
TI  - Complement inhibition as a proposed neuroprotective strategy following cardiac
      arrest.
AB  - Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with
      neurological injury accounting for a disproportionate amount of the morbidity and
      mortality following return of spontaneous circulation. A dearth of effective
      treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R)
      injury following successful resuscitation from OHCA. Emerging preclinical as well
      as recent human clinical evidence suggests that activation of the complement
      cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA.
      In addition, it is well established that complement inhibition improves outcome
      in both global and focal models of brain ischemia. Due to the profound impact of
      GCI/R injury following OHCA, and the relative lack of effective neuroprotective
      strategies for this pathologic process, complement inhibition provides an
      exciting opportunity to augment existing treatments to improve patient outcomes.
      To this end, this paper will explore the pathophysiology of complement-mediated
      GCI/R injury following OHCA.

PMID- 20150959
TI  - Regulation of chemokine production via oxidative pathway in HeLa cells.
AB  - Inflammation is associated with disease progression and, by largely unknown
      mechanisms, has been said to drive oncogenesis. At inflamed sites, neutrophils
      deploy a potent antimicrobial arsenal that includes proteinases, antimicrobial
      peptides, and ROS. Reactive oxygen species (ROSs) induce chemokines. In the
      present study, the concentrations of IL-8 in culture supernatants of HeLa cells
      treated with ROS were determined by enzyme-linked immunosorbent assay. We used o
      phenanthroline to deplete Fe(2+) in order to investigate the mechanisms through
      which ROSs induce IL-8 secretion in our system. The iron chelator o
      phenanthroline effectively inhibited H(2)O(2)-induced ERK2 activation. Enzyme
      linked immunosorbent assays showed that IL-8 protein secretion was elevated in
      ROS-treated HeLa cells. When Fe(2+) was removed from these cells, IL-8 secretion
      was inhibited. Collectively, these results indicate that Fe(2+)-mediated Erk
      pathway activation is an important signal transduction pathway in ROS-induced IL
      8 secretion in epithelial cells.

PMID- 20150960
TI  - Differential between protein and mRNA expression of CCR7 and SSTR5 receptors in
      Crohn's disease patients.
AB  - Crohn's disease (CD) is a multifactorial chronic inflammatory bowel disease of
      unknown cause. The aim of the present study was to explore if mRNA over
      expression of SSTR5 and CCR7 found in CD patients could be correlated to
      respective protein expression. When compared to healthy donors, SSTR5 was over
      expressed 417 +/- 71 times in CD peripheral blood mononuclear cells (PBMCs). Flow
      cytometry experiments showed no correlation between mRNA and protein expression
      for SSTR5 in PBMCs. In an attempt to find a reason of such a high mRNA
      expression, SSTR5 present on CD PBMCs were tested and found as biologically
      active as on healthy cells. In biopsies of CD intestinal tissue, SSTR5 was not
      over-expressed but CCR7, unchanged in PBMCs, was over-expressed by 10 +/- 3 times
      in the lamina propria. Confocal microscopy showed a good correlation of CCR7 mRNA
      and protein expression in CD intestinal biopsies. Our data emphasize flow and
      image cytometry as impossible to circumvent in complement to molecular biology so
      to avoid false interpretation on receptor expressions. Once confirmed by further
      large-scale studies, our preliminary results suggest a role for SSTR5 and CCR7 in
      CD pathogenesis.

PMID- 20150961
TI  - Activation of TLR4-mediated NFkappaB signaling in hemorrhagic brain in rats.
AB  - Inflammation and immunity play a crucial role in the pathogenesis of
      Intracerebral hemorrhage (ICH). Toll-like receptor 4- (TLR4-) mediated nuclear
      factor kappa-B (NFkappaB) signaling plays critical roles in the activation and
      regulation of inflammatory responses in injured brain. However, the involvement
      of TLR4-mediated NFkappaB signaling in the pathogenesis of ICH remains unknown.
      The present study was to evaluate the temporal profile of the expression of TLR4
      and the activation of TLR4-mediated NFkappaB signaling in brain tissues of Wistar
      rats after ICH. TLR4 mRNA and protein, the phosphorylation of inhibitors of kappa
      B (p-IkappaBalpha), and the activity of NFkappaB were examined in hemorrhagic
      cerebral tissue by Rt-PCR, Western blots, immunohistochemistry staining, and
      EMSA. Compared with saline control, the TLR4 mRNA and protein significantly
      increased starting at 6 hours after ICH, peaked on the 3rd day after ICH, and
      then decreased but still maintained at a higher level on the 7th day after ICH (P
      < .05). The level of p-IkappaBalpha and the activity of NFkappaB also increased
      in the brain after ICH compared with saline control. The present study firstly
      suggests that TLR4-mediated NFkappaB signaling participates in the pathogenesis
      of ICH, which may become a therapeutic target for ICH-induced brain damage.

PMID- 20150963
TI  - Leptin induces an inflammatory phenotype in lean Wistar rats.
AB  - The present study addressed the hypothesis that leptin promotes leukocyte
      trafficking into adipose tissue. Accordingly, male Wistar rats were treated with
      saline or recombinant rat leptin (1 mg/kg) via the tail vein. Leukocyte
      trafficking in mesenteric venules was quantified by intravital microscopy.
      Treatment with leptin resulted in a 3- and 5-fold increases in rolling and firm
      adhesion, respectively. Compared to vehicle controls, leptin enhanced mRNA levels
      of IL-6 (8-fold) and MCP-1 (5-fold) in mesenteric adipose tissue (MAT). Similar
      increases in these markers were observed in mesenteric venules and in liver.
      Finally, the direct effect of leptin was assessed in C3A hepatocytes treated with
      leptin for 24 hours (7.8 ng/mL-125 ng/mL). Consistent with observations in vivo,
      production of ICAM-1, MCP-1, and IL-6 by hepatocytes was increased significantly.
      These findings support the hypothesis that leptin directly initiates inflammation
      in the local environment of mesenteric adipose tissue as well as systemically.

PMID- 20150962
TI  - Leukotrienes in atherosclerosis: new target insights and future therapy
      perspectives.
AB  - Atherosclerosis represents an important chronic inflammatory process associated
      with several pathophysiological reactions in the vascular wall. The arachidonic
      acid, released by phospholipase A2, is an important substrate for the production
      of a group of lipid mediators known as leukotrienes, which induce proinflammatory
      signaling through the activation of specific BLT and CysLT receptors. The
      interaction of these substances in the vascular wall determines important
      morphological alterations like the early lipid retention and the accumulation of
      foam cells, the development of intimal hyperplasia, and advanced atherosclerotic
      lesions, and it plays an important role in the rupture of atherosclerotic plaque.
      Many studies regarding myocardial ischemia and reperfusion show that leukotriene
      signaling may be involved in the development of ischemic injury. For these,
      reasons both leukotriene synthesis inhibitors and leukotriene receptor
      antagonists have been suggested for inducing beneficial effects at different
      stages of the atherosclerosis process and may represent a new therapeutic target
      in the treatment of atherosclerotic vessel diseases, in particular in acute
      coronary syndrome.

PMID- 20150965
TI  - Improved label-free LC-MS analysis by wavelet-based noise rejection.
AB  - Label-free LC-MS analysis allows determining the differential expression level of
      proteins in multiple samples, without the use of stable isotopes. This technique
      is based on the direct comparison of multiple runs, obtained by continuous
      detection in MS mode. Only differentially expressed peptides are selected for
      further fragmentation, thus avoiding the bias toward abundant peptides typical of
      data-dependent tandem MS. The computational framework includes detection,
      alignment, normalization and matching of peaks across multiple sets, and several
      software packages are available to address these processing steps. Yet, more care
      should be taken to improve the quality of the LC-MS maps entering the pipeline,
      as this parameter severely affects the results of all downstream analyses. In
      this paper we show how the inclusion of a preprocessing step of background
      subtraction in a common laboratory pipeline can lead to an enhanced inclusion
      list of peptides selected for fragmentation and consequently to better protein
      identification.

PMID- 20150964
TI  - Synthetic biology: tools to design, build, and optimize cellular processes.
AB  - The general central dogma frames the emergent properties of life, which make
      biology both necessary and difficult to engineer. In a process engineering
      paradigm, each biological process stream and process unit is heavily influenced
      by regulatory interactions and interactions with the surrounding environment.
      Synthetic biology is developing the tools and methods that will increase control
      over these interactions, eventually resulting in an integrative synthetic biology
      that will allow ground-up cellular optimization. In this review, we attempt to
      contextualize the areas of synthetic biology into three tiers: (1) the process
      units and associated streams of the central dogma, (2) the intrinsic regulatory
      mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at
      each of these three tiers attempt to control cellular systems and take advantage
      of emerging tools and approaches. Ultimately, it will be possible to integrate
      these approaches and realize the vision of integrative synthetic biology when
      cells are completely rewired for biotechnological goals. This review will
      highlight progress towards this goal as well as areas requiring further research.

PMID- 20150966
TI  - Molecular modulation of intestinal epithelial barrier: contribution of
      microbiota.
AB  - The daunting task required of the gut-barrier to prevent luminal pathogens and
      harmful substances from entering into the internal milieu and yet promoting
      digestion and absorption of nutrients requires an exquisite degree of
      coordination between the different architectural units of this barrier. The
      complex integration and execution of these functions are superbly carried out by
      the intestinal mucosal (IM) surface. Exposed to trillions of luminal microbes,
      the IM averts threats by signaling to the innate immune system, through pattern
      recognition receptors (PRR), to respond to the commensal bacteria by developing
      tolerance (hyporesponsiveness) towards them. This system also acts by protecting
      against pathogens by elaborating and releasing protective peptides, cytokines,
      chemokines, and phagocytic cells. The IM is constantly sampling luminal contents
      and making molecular adjustments at its frontier. This article describes the
      topography of the IM and the mechanisms of molecular adjustments that protect the
      internal milieu, and also describes the role of the microbiota in achieving this
      goal.

PMID- 20150967
TI  - Immunity against helminths: interactions with the host and the intercurrent
      infections.
AB  - Helminth parasites are of considerable medical and economic importance. Studies
      of the immune response against helminths are of great interest in understanding
      interactions between the host immune system and parasites. Effector immune
      mechanisms against tissue-dwelling helminths and helminths localized in the lumen
      of organs, and their regulation, are reviewed. Helminth infections are
      characterized by an association of Th2-like and Treg responses. Worms are able to
      persist in the host and are mainly responsible for chronic infection despite a
      strong immune response developed by the parasitized host. Two types of protection
      against the parasite, namely, premune and partial immunities, have been
      described. Immune responses against helminths can also participate in
      pathogenesis. Th2/Treg-like immunomodulation allows the survival of both host and
      parasite by controlling immunopathologic disorders and parasite persistence.
      Consequences of the modified Th2-like responses on co-infection, vaccination, and
      inflammatory diseases are discussed.

PMID- 20150969
TI  - The Venturia apple pathosystem: pathogenicity mechanisms and plant defense
      responses.
AB  - Venturia inaequalis is the causal agent of apple scab, a devastating disease of
      apple. We outline several unique features of this pathogen which are useful for
      molecular genetics studies intended to understand plant-pathogen interactions.
      The pathogenicity mechanisms of the pathogen and overview of apple defense
      responses, monogenic and polygenic resistance, and their utilization in scab
      resistance breeding programs are also reviewed.

PMID- 20150970
TI  - Substance P signaling contributes to granuloma formation in Taenia crassiceps
      infection, a murine model of cysticercosis.
AB  - Cysticercosis is an infection with larval cysts of the cestode Taenia solium.
      Through pathways that are incompletely understood, dying parasites initiate a
      granulomatous reaction that, in the brain, causes seizures. Substance P (SP), a
      neuropeptide involved in pain-transmission, contributes to inflammation and
      previously was detected in granulomas associated with dead T. crassiceps cysts.
      To determine if SP contributes to granuloma formation, we measured granuloma-size
      and levels of IL-1beta, TNF-alpha, and IL-6 within granulomas in T. crassiceps
      infected wild type (WT) mice and mice deficient in SP-precursor (SPP) or the SP
      receptor (neurokinin 1, NK1). Granuloma volumes of infected SPP- and NK1-knockout
      mice were reduced by 31 and 36%, respectively, compared to WT mice (P < .05 for
      both) and produced up to 5-fold less IL-1beta, TNF-alpha, and IL-6 protein. Thus,
      SP signaling contributes to granuloma development and proinflammatory cytokine
      production in T. crassiceps infection and suggests a potential role for this
      mediator in human cystercercosis.

PMID- 20150968
TI  - Insights into the biology of IRES elements through riboproteomic approaches.
AB  - Translation initiation is a highly regulated process that exerts a strong
      influence on the posttranscriptional control of gene expression. Two alternative
      mechanisms govern translation initiation in eukaryotic mRNAs, the cap-dependent
      initiation mechanism operating in most mRNAs, and the internal ribosome entry
      site (IRES)-dependent mechanism, first discovered in picornaviruses. IRES
      elements are highly structured RNA sequences that, in most instances, require
      specific proteins for recruitment of the translation machinery. Some of these
      proteins are eukaryotic initiation factors. In addition, RNA-binding proteins
      (RBPs) play a key role in internal initiation control. RBPs are pivotal
      regulators of gene expression in response to numerous stresses, including virus
      infection. This review discusses recent advances on riboproteomic approaches to
      identify IRES transacting factors (ITAFs) and the relationship between RNA
      protein interaction and IRES activity, highlighting the most relevant features on
      picornavirus and hepatitis C virus IRESs.

PMID- 20150971
TI  - Hypercholesterolaemic serum increases the permeability of endothelial cells
      through zonula occludens-1 with phosphatidylinositol 3-kinase signaling pathway.
AB  - PURPOSE: Hypercholesterolemia and tight junctions play important roles in
      atherosclerosis. But the relationship between these two factors is unclear. In
      the present study, we investigated whether hypercholesterolemic serum could
      change the permeability of endothelial cells through altering expression and/or
      distribution of tight junction protein zonula occludens-1 (ZO-1).
      Phosphatidylinositol 3-kinase (PI3K) signaling pathway was also examined.
      MATERIALS AND METHODS: Cultured endothelial cells were treated with different
      concentration levels of hypercholesterolemic serum. The expression and
      distribution of ZO-1, the permeability of cultured cells and the involvement of
      PI3K signaling pathway were measured by various methods. RESULTS: In the present
      study, we found that hypercholesterolemic serum could not change the expression
      of ZO-1 either in mRNA or protein level. However, hypercholesterolemic serum
      could change the distribution of ZO-1 in cultured endothelial cells, and increase
      the permeability with a dose-dependent manner. When PI3K specific inhibitor
      wortmannin was used, the effects induced by hypercholesterolemic serum could be
      partly reversed. The role of PI3K signaling pathway was further confirmed by PI3K
      activity assay. CONCLUSIONS: Our results suggested that although
      hypercholesterolemic serum could not change the expression of ZO-1, it could
      change the distribution and increase the permeability in endothelial cells
      through PI3K signaling pathway.

PMID- 20150973
TI  - The Small Heat Shock Protein HSP25/27 (HspB1) Is Abundant in Cultured Astrocytes
      and Associated with Astrocytic Pathology in Progressive Supranuclear Palsy and
      Corticobasal Degeneration.
AB  - Filamentous tau-positive protein inclusions in neurons and glia are prominent
      features of a number of neurodegenerative disorders termed tauopathies. These
      inclusions are further characterized by the presence of heat shock proteins
      (HSPs). The group of small HSPs, namely, HSP27 and alphaB-crystallin, interact
      with the cytoskeleton, bind to nonnative proteins, and prevent their aggregation
      after stress. To further investigate their contribution to neurodegenerative
      diseases, we have analyzed the association of HSP27 with pathological lesions of
      tauopathies. Microarray and immunoblot analysis revealed that HSP27 is enhanced
      at the mRNA and protein levels in affected brains, and that it is associated with
      astrocytic pathology. The upregulation of HSP27 in tauopathies with gial
      pathology implies distinct mechanisms for glial and neuronal cells. This was
      sustained by cell culture studies, demonstrating that the small HSPs are
      specifically and prominently expressed in unstressed astrocytes and not in
      neurons and in neurons remained at a rather low level even after stress
      situations.

PMID- 20150974
TI  - Analysis of bio-obtainable endocrine disrupting metals in river water and
      sediment, sewage influent/effluent, sludge, leachate, and concentrated leachate,
      in the irish midlands shannon catchment.
AB  - The application of an acid digestion and subsequent solid-phase extraction (SPE)
      procedure were implemented as preliminary treatments prior to quantifying the
      levels of potentially endocrine disrupting metals (EDMs) in a variety of solid
      and liquid matrices. These included (solid) river sediment, leachate sediment and
      sewage sludge and also (liquid) river water, landfill leachate, concentrated
      leachate, sewage influent, and sewage effluent, sampled in the Irish Midlands.
      The total concentrations of cobalt (Co), cadmium (Cd), copper (Cu), chromium
      (Cr), nickel (Ni), lead (Pb), zinc (Zn), and manganese (Mn), after extraction and
      preconcentration, were determined by atomic absorption spectroscopy (AAS).
      Mercury (Hg) in sediment and sludge was determined using cold-vapour atomic
      fluorescence spectroscopy (AFS). For sewage sludge maximum values (mg/kg(dw)) of
      4700 Ni, 1642 Mn, 100.0 Cd, 3400 Zn, 36.70 Co, 750.0 Pb, 485.8 Cr, and 1003 Cu
      were determined whilst in leachate sediment, maximum values (mg/kg(dw)) of 32.10
      Ni, 815.0 Mn, 32.78 Cd, 230.3 Zn, 26.73 Co, 3525 Pb, 124.9 Cr, and 50.13 Cu were
      found. Over several months, the data showed elevated levels in sewage influents,
      effluents, and sludges compared to a battery of adjacent river water samples and
      corresponding sediments. There was a definite trend for target values for
      sediments to be exceeded, while intervention values were only exceeded for
      cadmium. Overall the pattern in terms of concentration was sewage > leachate >
      river matrices. A nonparametric assessment of the effect of sewage treatment
      method on median metal levels in sludge revealed statistically significant
      differences at the 95% level of confidence for Co, Cr, and Hg and at the 90%
      level of confidence for Cd.

PMID- 20150972
TI  - A new caspase-8 isoform caspase-8s increased sensitivity to apoptosis in Jurkat
      cells.
AB  - Caspase-8 is a key initiator of death receptor-induced apoptosis. Here we report
      a novel short isoform of caspase-8 (caspase-8s), which encodes the first (Death
      Effector Domain) DED and part of the second DED, missing the C-terminal caspase
      domain. In vivo binding assays showed that transfected caspase-8s bound to (Fas
      associated death domain protein) FADD, the adaptor protein in (death-induced
      signal complex) DISC. To investigate the potential effects of caspase-8s on cell
      apoptosis, Jurkat cells were stably transfected with caspase-8s. Overexpression
      of caspase-8s increased sensitivity to the apoptotic stimuli, Fas-agonistic
      antibody CH11. These results suggest that caspase-8s may act as a promoter of
      apoptosis through binding to FADD and is involved in the regulation of apoptosis.
      In addition, the results also indicate that the first DED was an important
      structure mediating combination between caspase-8 and FADD.

PMID- 20150975
TI  - Colorectal Carcinoma: Local Tumor Staging and Assessment of Lymph Node Metastasis
      by High-Resolution MR Imaging in Surgical Specimens.
AB  - Purpose. To assess the accuracy of high-resolution MR imaging as a means of
      evaluating mural invasion and lymph node metastasis by colorectal carcinoma in
      surgical specimens. Materials and Methods. High-resolution T1-weighted and T2
      weighted MR images were obtained in 92 surgical specimens containing 96
      colorectal carcinomas. Results. T2-weighted MR images clearly depicted the normal
      colorectal wall as consisting of seven layers. In 90 (94%) of the 96 carcinomas
      the depth of mural invasion depicted by MR imaging correlated well with the
      histopathologic stage. Nodal signal intensity on T2-weighted images (93%) and
      nodal border contour (93%) were more accurate than nodal size (89%) as indicators
      of lymph node metastasis, and MR imaging provided the highest accuracy (94%-96%)
      when they were combined. Conclusion. High-resolution MR imaging is a very
      accurate method for evaluating both mural invasion and lymph node metastasis by
      colorectal carcinoma in surgical specimens.

PMID- 20150976
TI  - Developmental Contexts and Mental Disorders Among Asian Americans.
AB  - In this article, we use age of immigration as a proxy for the developmental
      context for understanding the association between immigration experiences and
      mental health. Generation defines the context under which immigrants arrive in
      the United States. We drew data from the National Latino and Asian American Study
      (N = 2,095), the first ever study conducted on the mental health of a national
      sample of Asian Americans. Our findings reveal that age of immigration is linked
      to lifetime and 12-month rates of psychiatric disorder: Immigrants who arrive
      earlier in life are more likely to have both lifetime and 12-month disorders.
      U.S. born and immigrants who arrive as children are much more likely to have a
      mental disorder in their lifetimes than other immigrant generations.

PMID- 20150977
TI  - Potential of phage-displayed peptide library technology to identify functional
      targeting peptides.
AB  - Combinatorial peptide library technology is a valuable resource for drug
      discovery and development. Several peptide drugs developed through phage
      displayed peptide library technology are presently in clinical trials and the
      authors envision that phage-displayed peptide library technology will assist in
      the discovery and development of many more. This review attempts to compile and
      summarize recent literature on targeting peptides developed through peptide
      library technology, with special emphasis on novel peptides with targeting
      capacity evaluated in vivo.

PMID- 20150979
TI  - Overexpression of bacterial ethylene-forming enzyme gene in Trichoderma reesei
      enhanced the production of ethylene.
AB  - In order to efficiently utilize natural cellulose materials to produce ethylene,
      three expression vectors containing the ethylene-forming enzyme (efe) gene from
      Pseudomonas syringae pv. glycinea were constructed. The target gene was
      respectively controlled by different promoters: cbh I promoter from Trichoderma
      reesei cellobiohydrolases I gene, gpd promoter from Aspergillus nidulans
      glyceraldehyde-3-phosphate dehydrogenase gene and pgk I promoter from T. reesei 3
      phosphoglycerate kinase I gene. After transforming into T. reesei QM9414, 43
      stable transformants were obtained by PCR amplification and ethylene
      determination. Southern blot analysis of 14 transformants demonstrated that the
      efe gene was integrated into chromosomal DNA with copy numbers from 1 to 4.
      Reverse transcription polymerase chain reaction (RT-PCR) analysis of 6
      transformants showed that the heterologous gene was transcribed. By using wheat
      straw as a carbon source, the ethylene production rates of aforementioned 14
      transformants were measured. Transformant C30-3 with pgk I promoter had the
      highest ethylene production (4,012 nl h(-1) l(-1)). This indicates that
      agricultural wastes could be used to produce ethylene in recombinant filamentous
      fungus T. reesei.

PMID- 20150981
TI  - An asymptomatic case of peritoneal encapsulation: case report and review of the
      literature.
AB  - Peritoneal encapsulation is a rare congenital anomaly characterised by a thin
      membrane of peritoneum encasing the small bowel to form an accessory peritoneal
      sac. We present a case of peritoneal encapsulation diagnosed incidentally in an
      82 year old man undergoing laparotomy for colonic cancer. The sac was easily
      excised and surgery was otherwise uneventful. A discussion of the case and a
      review of the literature are presented.

PMID- 20150980
TI  - Expression and functional activity of nucleoside transporters in human choroid
      plexus.
AB  - BACKGROUND: Human equilibrative nucleoside transporters (hENTs) 1-3 and human
      concentrative nucleoside transporters (hCNTs) 1-3 in the human choroid plexus
      (hCP) play a role in the homeostasis of adenosine and other naturally occurring
      nucleosides in the brain; in addition, hENT1, hENT2 and hCNT3 mediate membrane
      transport of nucleoside reverse transcriptase inhibitors that could be used to
      treat HIV infection, 3'-azido-3'-deoxythymidine, 2'3'-dideoxycytidine and 2'3'
      dideoxyinosine. This study aimed to explore the expression levels and functional
      activities of hENTs 1-3 and hCNTs 1-3 in human choroid plexus. METHODS: Freshly
      isolated pieces of lateral ventricle hCP, removed for various clinical reasons
      during neurosurgery, were obtained under Local Ethics Committee approval.
      Quantification of mRNAs that encoded hENTs and hCNTs was performed by the
      hydrolysis probes-based reverse transcription real time-polymerase chain reaction
      (RT-qPCR); for each gene of interest and for 18 S ribosomal RNA, which was an
      endogenous control, the efficiency of PCR reaction (E) and the quantification
      cycle (Cq) were calculated. The uptake of [(3)H]inosine by the choroid plexus
      pieces was investigated to explore the functional activity of hENTs and hCNTs in
      the hCP. RESULTS: RT-qPCR revealed that the mRNA encoding the intracellularly
      located transporter hENT3 was the most abundant, with E(-Cq )value being only
      about 40 fold less that the E(-Cq )value for 18 S ribosomal RNA; mRNAs encoding
      hENT1, hENT2 and hCNT3 were much less abundant than mRNA for the hENT3, while
      mRNAs encoding hCNT1 and hCNT2 were of very low abundance and not detectable.
      Uptake of [(3)H]inosine by the CP samples was linear and consisted of an Na(+)
      dependent component, which was probably mediated by hCNT3, and Na(+)-independent
      component, mediated by hENTs. The latter component was not sensitive to
      inhibition by S-(4-nitrobenzyl)-6-thioinosine (NBMPR), when used at a
      concentration of 0.5 muM, a finding that excluded the involvement of hENT1, but
      it was very substantially inhibited by 10 muM NBMPR, a finding that suggested the
      involvement of hENT2 in uptake. CONCLUSION: Transcripts for hENT1-3 and hCNT3
      were detected in human CP; mRNA for hENT3, an intracellularly located nucleoside
      transporter, was the most abundant. Human CP took up radiolabelled inosine by
      both concentrative and equilibrative processes. Concentrative uptake was probably
      mediated by hCNT3; the equilibrative uptake was mediated only by hENT2. The hENT1
      transport activity was absent, which could suggest either that this protein was
      absent in the CP cells or that it was confined to the basolateral side of the CP
      epithelium.

PMID- 20150978
TI  - Astatine Radiopharmaceuticals: Prospects and Problems.
AB  - For the treatment of minimum residual diseases such micrometastases and residual
      tumor margins that remain after debulking of the primary tumor, targeted
      radiotherapy using radiopharmaceuticals tagged with alpha-particle-emitting
      radionuclides is very attractive. In addition to the their short range in tissue,
      which helps minimize harmful effects on adjacent normal tissues, alpha-particles,
      being high LET radiation, have several radiobiological advantages. The heavy
      halogen, astatine-211 is one of the prominent alpha-particle-emitting
      radionuclides in practice. Being a halogen, it can often be incorporated into
      biomolecules of interest by adapting radioiodination chemistry. A wide spectrum
      of compounds from the simple [(211)At]astatide ion to small organic molecules,
      peptides, and large proteins labeled with (211)At have been investigated with at
      least two reaching the stage of clinical evaluation. The chemistry, cytotoxic
      advantages, biodistribution studies, and microdosimetry/pharmacokinetic modeling
      of some of these agents will be reviewed. In addition, potential problems such as
      the harmful effect of radiolysis on the synthesis, lack of sufficient in vivo
      stability of astatinated compounds, and possible adverse effects when they are
      systemically administered will be discussed.

PMID- 20150982
TI  - Successful treatment of tracheal stenosis by rigid bronchoscopy and topical
      mitomycin C: a case report.
AB  - Tracheal stenosis is a known complication of prolonged intubation. It is
      difficult to treat and traditional surgical approach is associated with
      significant risk and complications. Recurrent stenosis due to granulation tissue
      necessitates repeated procedures. We describe a case of short web-like tracheal
      stenosis (concentric membranous stenosis less than 1 cm in length without
      associated cartilage damage) managed by a minimally invasive thoracic endoscopic
      approach. Topical application of Mitomycin C, a potent fibroblast inhibitor
      reduces granulation tissue formation and prevents recurrence.

PMID- 20150983
TI  - Failure of asnis iii 5.0 mm cannulated screw: a case report.
AB  - We describe a case of an ASNIS III 5.0 mm partially threaded cannulated screw
      unthreading itself as it was being inserted during fracture fixation of a
      humerus. The majority of complications associated with cannulated screws involve
      breaking of the screw, as opposed to unthreading. We believe that the self
      tapping design of the screw, in combination with the cannulated design, creates a
      potential area of weakness when used on hard bone.

PMID- 20150984
TI  - Experimental models for analysis of oligodendrocyte pathophysiology in stroke.
AB  - White matter damage is a clinically important part of stroke. However, compared
      to the mechanisms of neuronal injury in gray matter, white matter pathophysiology
      remains relatively understudied and poorly understood. This mini-review aims at
      summarizing current knowledge on experimental systems for analyzing the role of
      white matter injury relevant to stroke. In vitro platforms comprise primary
      cultures of both mature oligodendrocytes (OLGs) as well as oligodendrocyte
      precursor cells (OPCs). Tissue platforms involve preparations of optic nerve
      systems. Whole-animal platforms comprise in vivo models of cerebral ischemia that
      attempt to target white matter brain areas. While there is no single perfect
      model system, the collection of these experimental approaches have recently
      allowed a better understanding of the molecular and cellular pathways underlying
      OLG/OPC damage and demyelination. A systematic utilization of these cell, tissue
      and whole-animal platforms may eventually lead us to discover new targets for
      treating white matter injury in stroke and other CNS disorders.

PMID- 20150985
TI  - Animal models of focal brain ischemia.
AB  - Stroke is a leading cause of disability and death in many countries.
      Understanding the pathophysiology of ischemic injury and developing therapies is
      an important endeavor that requires much additional research. Animal stroke
      models provide an important mechanism for these activities. A large number of
      stroke models have been developed and are currently used in laboratories around
      the world. These models are overviewed as are approaches for measuring infarct
      size and functional outcome.

PMID- 20150987
TI  - Facilitating needs based cancer care for people with a chronic disease:
      Evaluation of an intervention using a multi-centre interrupted time series
      design.
AB  - BACKGROUND: Palliative care should be provided according to the individual needs
      of the patient, caregiver and family, so that the type and level of care
      provided, as well as the setting in which it is delivered, are dependent on the
      complexity and severity of individual needs, rather than prognosis or diagnosis
      [1]. This paper presents a study designed to assess the feasibility and efficacy
      of an intervention to assist in the allocation of palliative care resources
      according to need, within the context of a population of people with advanced
      cancer. METHODS/DESIGN: People with advanced cancer and their caregivers
      completed bi-monthly telephone interviews over a period of up to 18 months to
      assess unmet needs, anxiety and depression, quality of life, satisfaction with
      care and service utilisation. The intervention, introduced after at least two
      baseline phone interviews, involved a) training medical, nursing and allied
      health professionals at each recruitment site on the use of the Palliative Care
      Needs Assessment Guidelines and the Needs Assessment Tool: Progressive Disease -
      Cancer (NAT: PD-C); b) health professionals completing the NAT: PD-C with
      participating patients approximately monthly for the rest of the study period.
      Changes in outcomes will be compared pre-and post-intervention. DISCUSSION: The
      study will determine whether the routine, systematic and regular use of the
      Guidelines and NAT: PD-C in a range of clinical settings is a feasible and
      effective strategy for facilitating the timely provision of needs based care.
      TRIALS REGISTRATION: ISRCTN21699701.

PMID- 20150988
TI  - Biomarkers in psychiatry: drawbacks and potential for misuse.
AB  - For more than 20 years, researchers have attempted to identify diagnostic and
      prognostic biomarkers for psychiatric disorders including schizophrenia, major
      (unipolar) depression, and bipolar disorder. Advocates of this research contend
      that identifying such biomarkers will aid in the diagnosis of these disorders, as
      well as the possible development of effective psychiatric medications to treat
      them. Currently, there are no diagnostic tests available. This is largely due to
      the multi-factorial nature of psychiatric disorders. Biomarker testing of
      individuals is also prohibitively expensive because significant expertise is
      required to conduct tests and follow-up counseling for the patient is often
      necessary. It is cautioned that widespread biomarker testing could lead to
      negative consequences such as discrimination in health insurance and employment,
      as well as selective abortion.

PMID- 20150986
TI  - Rodent models of focal cerebral ischemia: procedural pitfalls and translational
      problems.
AB  - Rodent models of focal cerebral ischemia are essential tools in experimental
      stroke research. They have added tremendously to our understanding of injury
      mechanisms in stroke and have helped to identify potential therapeutic targets. A
      plethora of substances, however, in particular an overwhelming number of putative
      neuroprotective agents, have been shown to be effective in preclinical stroke
      research, but have failed in clinical trials. A lot of factors may have
      contributed to this failure of translation from bench to bedside. Often, deficits
      in the quality of experimental stroke research seem to be involved. In this
      article, we review the commonest rodent models of focal cerebral ischemia -
      middle cerebral artery occlusion, photothrombosis, and embolic stroke models -
      with their respective advantages and problems, and we address the issue of
      quality in preclinical stroke modeling as well as potential reasons for
      translational failure.

PMID- 20150989
TI  - The importance of the discourse on the method.

PMID- 20150990
TI  - Interleukin-18 does not influence infarct volume or functional outcome in the
      early stage after transient focal brain ischemia in mice.
AB  - Interleukin-18 (IL-18) is a proinflammatory cytokine of the interleukin-1 family
      which is upregulated after cerebral ischemia. The functional role of IL-18 in
      cerebral ischemia is unknown. In the present study, we compared infarct size in
      IL-18 knock-out and wild-type mice 24 hours and 48 hours after 1-hour transient
      middle cerebral artery occlusion (tMCAO). Moreover, the functional outcome was
      evaluated in a modified Bederson score, foot fault test and grip test. There were
      no significant differences in infarct size or functional outcome tests between
      wild-type and IL-18 knock-out mice. These data indicate that the early
      inflammatory response to cerebral ischemia does not involve IL-18, in contrast to
      other interleukin-1 family members such as interleukin-1.

PMID- 20150991
TI  - Differentiation of the brain vasculature: the answer came blowing by the Wnt.
AB  - Vascularization of the vertebrate brain takes place during embryonic development
      from a preformed perineural vascular plexus. As a consequence of the intimate
      contact with neuroectodermal cells the vessels, which are entering the brain
      exclusively via sprouting angiogenesis, acquire and maintain unique barrier
      properties known as the blood-brain barrier (BBB). The endothelial BBB depends
      upon the close association of endothelial cells with pericytes, astrocytes,
      neurons and microglia, which are summarized in the term neuro-vascular unit.
      Although it is known since decades that the CNS tissue provides the cues for BBB
      induction and differentiation in endothelial cells, the molecular mechanism
      remained obscure.Only recently, the canonical Wnt/beta-catenin pathway and the
      Wnt7a/7b growth factors have been implicated in brain angiogenesis on the one
      hand and in BBB induction on the other. This breakthrough in understanding the
      differentiation of the brain vasculature prompted us to review these findings
      embedded in the emerging concepts of Wnt signaling in the vasculature. In
      particular, interactions with other pathways that are crucial for vascular
      development such as VEGF, Notch, angiopoietins and Sonic hedgehog are discussed.
      Finally, we considered the potential role of the Wnt pathway in vascular brain
      pathologies in which BBB function is hampered, as for example in glioma, stroke
      and Alzheimer's disease.

PMID- 20150992
TI  - Ascorbate inhibition of angiogenesis in aortic rings ex vivo and subcutaneous
      Matrigel plugs in vivo.
AB  - BACKGROUND: Angiogenesis is critical to tumor growth and is therefore a potential
      target for cancer therapy. As many current inhibitors of angiogenesis exhibit
      host toxicity, natural alternatives are needed. At millimolar concentrations,
      ascorbate (vitamin C) inhibits migration and tubule formation by mature
      endothelial cells and endothelial progenitors. In the present study, we examined
      the effects of ascorbate, at levels relevant during intravenous infusion therapy,
      on angiogenesis using an ex vivo an in vivo assay. METHODS: Two assays were used
      to evaluate effect of high-doses ascorbic acid on angiogenesis: ex vivo rat
      aortic ring explant assay in Matrigel matrices and in vivo Matrigel plug assay.
      In aortic rings, we quantified microvessel growth, branching and vessel
      regression under different treatment conditions. In murine angiogenesis assay,
      male C57 mice 6-8 weeks old were treated by high-dose ascorbic acid and the
      number of microvessels was analyzed by histological method. To characterize the
      population of cells that formed capillary network and microvessels, the sections
      were stained by CD34 and CD31 antibodies. RESULTS: Results show that sprouting of
      endothelial tubules from aortic rings was reduced in a concentration-dependent
      fashion by ascorbate: while controls roughly tripled sprout densities during the
      study, ascorbate (1 mg/mL, 5.5 mM) actually reduced sprout density. In vivo, the
      ability of mice to vascularize subcutaneously implanted Matrigel plug was
      diminished if the mice were treated with 430 mg/kg vitamin C: numbers of vessels,
      and vessel densities, in plugs from treated mice were roughly 30% less than those
      in plugs from untreated mice. CONCLUSIONS: We conclude that the inhibition of
      angiogenesis by ascorbate suggested in vitro is confirmed in vivo, and that
      angiogenesis inhibition may be one mechanism by which intravenous ascorbate
      therapy shows efficacy in animal experiments and clinical case studies.

PMID- 20150993
TI  - Furfural induces reactive oxygen species accumulation and cellular damage in
      Saccharomyces cerevisiae.
AB  - BACKGROUND: Biofuels offer a viable alternative to petroleum-based fuel. However,
      current methods are not sufficient and the technology required in order to use
      lignocellulosic biomass as a fermentation substrate faces several challenges. One
      challenge is the need for a robust fermentative microorganism that can tolerate
      the inhibitors present during lignocellulosic fermentation. These inhibitors
      include the furan aldehyde, furfural, which is released as a byproduct of pentose
      dehydration during the weak acid pretreatment of lignocellulose. In order to
      survive in the presence of furfural, yeast cells need not only to reduce furfural
      to the less toxic furan methanol, but also to protect themselves and repair any
      damage caused by the furfural. Since furfural tolerance in yeast requires a
      functional pentose phosphate pathway (PPP), and the PPP is associated with
      reactive oxygen species (ROS) tolerance, we decided to investigate whether or not
      furfural induces ROS and its related cellular damage in yeast. RESULTS: We
      demonstrated that furfural induces the accumulation of ROS in Saccharomyces
      cerevisiae. In addition, furfural was shown to cause cellular damage that is
      consistent with ROS accumulation in cells which includes damage to mitochondria
      and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural
      induced damage is less severe when yeast are grown in a furfural concentration
      (25 mM) that allows for eventual growth after an extended lag compared to a
      concentration of furfural (50 mM) that prevents growth. CONCLUSION: These data
      suggest that when yeast cells encounter the inhibitor furfural, they not only
      need to reduce furfural into furan methanol but also to protect themselves from
      the cellular effects of furfural and repair any damage caused. The reduced
      cellular damage seen at 25 mM furfural compared to 50 mM furfural may be linked
      to the observation that at 25 mM furfural yeast were able to exit the furfural
      induced lag phase and resume growth. Understanding the cellular effects of
      furfural will help direct future strain development to engineer strains capable
      of tolerating or remediating ROS and the effects of ROS.

PMID- 20150994
TI  - The Nordic back pain subpopulation program: course patterns established through
      weekly follow-ups in patients treated for low back pain.
AB  - BACKGROUND: Low back pain (LBP) is known to have a fluctuating course. In
      clinical studies, when deciding on duration of treatment and time for follow-up,
      it is important to know at what point in time a definite pattern of recovery
      becomes apparent and at what time a possible recurrence is likely to occur. A
      detailed description of the pain pattern has been difficult to establish with
      commonly used methods for follow-up, and we now introduce data collection by
      means of text messaging on mobile phones. The purpose of this study was to
      describe the detailed course of LBP during 18 weeks in a population treated in
      the primary care sector by chiropractors. METHODS: The study population consisted
      of 78 patients presenting to a chiropractor with LBP, who for at least 12 weeks
      responded to the questions sent by text messaging concerning 1) the number of LBP
      days the preceding week and 2) the intensity of present LBP. RESULTS: A rapid
      improvement was observed through weeks one to four. After week seven no further
      improvement happened, and from the 12(th )week there seemed to be a tendency
      towards worsening. CONCLUSIONS: We suggest that follow-ups in studies concerning
      primary sector LBP care are conducted in week seven after treatment was initiated
      and at some later point which cannot be established from this study. In clinical
      practice we recommend that patients' LBP status is systematically followed for
      the first four weeks since lack of improvement during that period should cause
      watchfulness.

PMID- 20150995
TI  - Optimal assignment methods for ligand-based virtual screening.
AB  - BACKGROUND: Ligand-based virtual screening experiments are an important task in
      the early drug discovery stage. An ambitious aim in each experiment is to
      disclose active structures based on new scaffolds. To perform these "scaffold
      hoppings" for individual problems and targets, a plethora of different similarity
      methods based on diverse techniques were published in the last years. The optimal
      assignment approach on molecular graphs, a successful method in the field of
      quantitative structure-activity relationships, has not been tested as a ligand
      based virtual screening method so far. RESULTS: We evaluated two already
      published and two new optimal assignment methods on various data sets. To
      emphasize the "scaffold-hopping" ability, we used the information of chemotype
      clustering analyses in our evaluation metrics. Comparisons with literature
      results show an improved early recognition performance and comparable results
      over the complete data set. A new method based on two different assignment steps
      shows an increased "scaffold-hopping" behavior together with a good early
      recognition performance. CONCLUSION: The presented methods show a good
      combination of chemotype discovery and enrichment of active structures.
      Additionally, the optimal assignment on molecular graphs has the advantage to
      investigate and interpret the mappings, allowing precise modifications of
      internal parameters of the similarity measure for specific targets. All methods
      have low computation times which make them applicable to screen large data sets.

PMID- 20150996
TI  - Application of the PM6 semi-empirical method to modeling proteins enhances
      docking accuracy of AutoDock.
AB  - BACKGROUND: Molecular docking methods are commonly used for predicting binding
      modes and energies of ligands to proteins. For accurate complex geometry and
      binding energy estimation, an appropriate method for calculating partial charges
      is essential. AutoDockTools software, the interface for preparing input files for
      one of the most widely used docking programs AutoDock 4, utilizes the Gasteiger
      partial charge calculation method for both protein and ligand charge calculation.
      However, it has already been shown that more accurate partial charge calculation 
      and as a consequence, more accurate docking- can be achieved by using quantum
      chemical methods. For docking calculations quantum chemical partial charge
      calculation as a routine was only used for ligands so far. The newly developed
      Mozyme function of MOPAC2009 allows fast partial charge calculation of proteins
      by quantum mechanical semi-empirical methods. Thus, in the current study, the
      effect of semi-empirical quantum-mechanical partial charge calculation on docking
      accuracy could be investigated. RESULTS: The docking accuracy of AutoDock 4 using
      the original AutoDock scoring function was investigated on a set of 53 protein
      ligand complexes using Gasteiger and PM6 partial charge calculation methods. This
      has enabled us to compare the effect of the partial charge calculation method on
      docking accuracy utilizing AutoDock 4 software. Our results showed that the
      docking accuracy in regard to complex geometry (docking result defined as
      accurate when the RMSD of the first rank docking result complex is within 2 A of
      the experimentally determined X-ray structure) significantly increased when
      partial charges of the ligands and proteins were calculated with the semi
      empirical PM6 method. Out of the 53 complexes analyzed in the course of our
      study, the geometry of 42 complexes were accurately calculated using PM6 partial
      charges, while the use of Gasteiger charges resulted in only 28 accurate
      geometries. The binding affinity estimation was not influenced by the partial
      charge calculation method - for more accurate binding affinity prediction
      development of a new scoring function for AutoDock is needed. CONCLUSION: Our
      results demonstrate that the accuracy of determination of complex geometry using
      AutoDock 4 for docking calculation greatly increases with the use of quantum
      chemical partial charge calculation on both the ligands and proteins.

PMID- 20150997
TI  - Software platform virtualization in chemistry research and university teaching.
AB  - BACKGROUND: Modern chemistry laboratories operate with a wide range of software
      applications under different operating systems, such as Windows, LINUX or Mac OS
      X. Instead of installing software on different computers it is possible to
      install those applications on a single computer using Virtual Machine software.
      Software platform virtualization allows a single guest operating system to
      execute multiple other operating systems on the same computer. We apply and
      discuss the use of virtual machines in chemistry research and teaching
      laboratories. RESULTS: Virtual machines are commonly used for cheminformatics
      software development and testing. Benchmarking multiple chemistry software
      packages we have confirmed that the computational speed penalty for using virtual
      machines is low and around 5% to 10%. Software virtualization in a teaching
      environment allows faster deployment and easy use of commercial and open source
      software in hands-on computer teaching labs. CONCLUSION: Software virtualization
      in chemistry, mass spectrometry and cheminformatics is needed for software
      testing and development of software for different operating systems. In order to
      obtain maximum performance the virtualization software should be multi-core
      enabled and allow the use of multiprocessor configurations in the virtual machine
      environment. Server consolidation, by running multiple tasks and operating
      systems on a single physical machine, can lead to lower maintenance and hardware
      costs especially in small research labs. The use of virtual machines can prevent
      software virus infections and security breaches when used as a sandbox system for
      internet access and software testing. Complex software setups can be created with
      virtual machines and are easily deployed later to multiple computers for hands-on
      teaching classes. We discuss the popularity of bioinformatics compared to
      cheminformatics as well as the missing cheminformatics education at universities
      worldwide.

PMID- 20150999
TI  - Virtual screening of bioassay data.
AB  - BACKGROUND: There are three main problems associated with the virtual screening
      of bioassay data. The first is access to freely-available curated data, the
      second is the number of false positives that occur in the physical primary
      screening process, and finally the data is highly-imbalanced with a low ratio of
      Active compounds to Inactive compounds. This paper first discusses these three
      problems and then a selection of Weka cost-sensitive classifiers (Naive Bayes,
      SVM, C4.5 and Random Forest) are applied to a variety of bioassay datasets.
      RESULTS: Pharmaceutical bioassay data is not readily available to the academic
      community. The data held at PubChem is not curated and there is a lack of
      detailed cross-referencing between Primary and Confirmatory screening assays.
      With regard to the number of false positives that occur in the primary screening
      process, the analysis carried out has been shallow due to the lack of cross
      referencing mentioned above. In six cases found, the average percentage of false
      positives from the High-Throughput Primary screen is quite high at 64%. For the
      cost-sensitive classification, Weka's implementations of the Support Vector
      Machine and C4.5 decision tree learner have performed relatively well. It was
      also found, that the setting of the Weka cost matrix is dependent on the base
      classifier used and not solely on the ratio of class imbalance. CONCLUSIONS:
      Understandably, pharmaceutical data is hard to obtain. However, it would be
      beneficial to both the pharmaceutical industry and to academics for curated
      primary screening and corresponding confirmatory data to be provided. Two
      benefits could be gained by employing virtual screening techniques to bioassay
      data. First, by reducing the search space of compounds to be screened and
      secondly, by analysing the false positives that occur in the primary screening
      process, the technology may be improved. The number of false positives arising
      from primary screening leads to the issue of whether this type of data should be
      used for virtual screening. Care when using Weka's cost-sensitive classifiers is
      needed - across the board misclassification costs based on class ratios should
      not be used when comparing differing classifiers for the same dataset.

PMID- 20150998
TI  - Application of 3D Zernike descriptors to shape-based ligand similarity searching.
AB  - BACKGROUND: The identification of promising drug leads from a large database of
      compounds is an important step in the preliminary stages of drug design. Although
      shape is known to play a key role in the molecular recognition process, its
      application to virtual screening poses significant hurdles both in terms of the
      encoding scheme and speed. RESULTS: In this study, we have examined the efficacy
      of the alignment independent three-dimensional Zernike descriptor (3DZD) for fast
      shape based similarity searching. Performance of this approach was compared with
      several other methods including the statistical moments based ultrafast shape
      recognition scheme (USR) and SIMCOMP, a graph matching algorithm that compares
      atom environments. Three benchmark datasets are used to thoroughly test the
      methods in terms of their ability for molecular classification, retrieval rate,
      and performance under the situation that simulates actual virtual screening tasks
      over a large pharmaceutical database. The 3DZD performed better than or
      comparable to the other methods examined, depending on the datasets and
      evaluation metrics used. Reasons for the success and the failure of the shape
      based methods for specific cases are investigated. Based on the results for the
      three datasets, general conclusions are drawn with regard to their efficiency and
      applicability. CONCLUSION: The 3DZD has unique ability for fast comparison of
      three-dimensional shape of compounds. Examples analyzed illustrate the advantages
      and the room for improvements for the 3DZD.

PMID- 20151000
TI  - Interpretable correlation descriptors for quantitative structure-activity
      relationships.
AB  - BACKGROUND: The topological maximum cross correlation (TMACC) descriptors are
      alignment-independent 2D descriptors for the derivation of QSARs. TMACC
      descriptors are generated using atomic properties determined by molecular
      topology. Previous validation (J Chem Inf Model 2007, 47: 626-634) of the TMACC
      descriptor suggests it is competitive with the current state of the art. RESULTS:
      Here, we illustrate the interpretability of the TMACC descriptors, through the
      analysis of the QSARs of inhibitors of angiotensin converting enzyme (ACE) and
      dihydrofolate reductase (DHFR). In the case of the ACE inhibitors, the TMACC
      interpretation shows features specific to C-domain inhibition, which have not
      been explicitly identified in previous QSAR studies. CONCLUSIONS: The TMACC
      interpretation can provide new insight into the structure-activity relationships
      studied. Freely available, open source software for generating the TMACC
      descriptors can be downloaded from http://comp.chem.nottingham.ac.uk.

PMID- 20151001
TI  - Economic recession and health of the people.

PMID- 20151002
TI  - Application of mass spectrometry-based proteomics for biomarker discovery in
      neurological disorders.
AB  - Mass spectrometry-based quantitative proteomics has emerged as a powerful
      approach that has the potential to accelerate biomarker discovery, both for
      diagnostic as well as therapeutic purposes. Proteomics has traditionally been
      synonymous with 2D gels but is increasingly shifting to the use of gel-free
      systems and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).
      Quantitative proteomic approaches have already been applied to investigate
      various neurological disorders, especially in the context of identifying
      biomarkers from cerebrospinal fluid and serum. This review highlights the scope
      of different applications of quantitative proteomics in understanding
      neurological disorders with special emphasis on biomarker discovery.

PMID- 20151003
TI  - Differential diagnosis of white matter diseases in the tropics: An overview.
AB  - In hospitals in the tropics, the availability of magnetic resonance imaging (MRI)
      facilities in urban areas and especially in teaching institutions have resulted
      in white matter diseases being frequently reported in a variety of clinical
      settings. Unlike the west where multiple sclerosis (MS) is the commonest white
      matter disease encountered, in the tropics, there are myriad causes for the same.
      Infectious and post infectious disorders probably account for the vast majority
      of these diseases. Human immunodeficiency virus (HIV) infection tops the list of
      infective conditions. Central nervous system (CNS) tuberculosis occasionally
      presents with patchy parenchymal lesions unaccompanied by meningeal involvement.
      Human T cell leukemia virus (HTLV) infection and cystic inflammatory lesions such
      as neurocysticercosis are important causes to be considered in the differential
      diagnosis. Diagnosing post infectious demyelinating disorders is equally
      challenging since more than a third of cases seen in the tropics do not present
      with history of past infection or vaccinations. Metabolic and deficiency
      disorders such as Wernicke's encephalopathy, osmotic demyelinating syndrome
      associated with extra pontine lesions and Vitamin B12 deficiency states can
      occassionaly cause confusion in diagnosis. This review considers a few important
      disorders which manifest with white matter changes on MRI and create diagnostic
      difficulties in a population in the tropics.

PMID- 20151004
TI  - Quadruple H therapy for vasospasm.
AB  - Triple H therapy has been enthusiastically used to increase cerebral blood flow
      in cases of vasospasm. Nevertheless, the oxygen-carrying capacity of the blood is
      lowered with this treatment. This side effect can theoretically be partially
      corrected using hyperbaric oxygen therapy (HBO) which appears to be the missing
      ring in the above therapeutic regimen. We conducted a review of of the available
      evidence regarding the beneficial effects of HBO in preventing postoperative
      ischemic complications due to vasospasm after surgery on ruptured cerebral
      aneurysms and the rationale for including HBO into the standards of care of these
      difficult patients.

PMID- 20151005
TI  - Cognition in type 2 diabetes: Association with vascular risk factors,
      complications of diabetes and depression.
AB  - BACKGROUND: The role of variables like duration of diabetes, diabetic control and
      microvascular complications in the causation of cognitive decline in patients
      with type 2 diabetes is not well studied. The contribution of hypertension to the
      cognitive decline in nondemented diabetic patients is unclear. AIMS: We wanted to
      see if cognition in patients with type 2 diabetes is associated with the duration
      of diabetes, control of diabetes, complications of diabetes, vascular risk
      factors, or depression. We also looked at association of noncompliance with
      cognition, and depression. SETTINGS AND DESIGN: We recruited ambulant patients
      with type 2 diabetes who are 55 years or more in age from the weekly diabetic
      clinic. We excluded patients with past history of stroke. METHODS AND MATERIAL:
      We selected the time taken for the Trial A test, delayed recall on ten-word list
      from Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Rowland
      Universal Dementia Assessment Scale (RUDAS) and Centre for Epidemiologic Studies
      Depression scale (CES-D) screening instrument to assess these patients.
      STATISTICAL ANALYSIS USED: We utilized mean, standard deviation, Chi-square test
      and Pearson's correlation for statistical analysis. We considered P < 0.05 to be
      significant. RESULTS: RUDAS scores inversely correlated (r = -0.360) with CES-D
      scores (P = 0.002). Scores of the screening instrument for depression, the CES-D
      was associated with the duration of diabetes mellitus (P = 0.018), fasting blood
      glucose (P = 0.029) as well as with 2-hour post prandial blood glucose (P =
      0.017). CONCLUSIONS: There is correlation between depression and global cognitive
      score. Depression seems to be associated with duration of diabetes and control of
      diabetes.

PMID- 20151006
TI  - Fine motor skills disorders in the course of Wilson's disease.
AB  - OBJECTIVES: Fine motor skills disorders belong to the neurological manifestation
      of Wilson's disease. The aim of this study is to investigate if fine motor
      performance changes during the course of the disease and with therapy. METHODS:
      In 15 neurological patients with Wilson's disease, severity of neurological
      symptoms was assessed with a neurology score. A test battery consisting of the
      hand writing of a test sentence, lines of "double-I" and retracing a circle was
      carried out for analysis. By means of a computer-aided analysis of the patient's
      handwriting, 10 kinematic parameters of the writing trace were calculated. These
      parameters were determined once at the very beginning of the study and then again
      after 7 years. RESULTS: Improvement of clinical symptoms was observed after onset
      of therapy only within the first 2 years. In contrast to the standard population,
      a reduced degree of automation could be detected both at the beginning and at the
      end of the 7-year interval. There was no significant change in 8 out of the 10
      kinematic parameters during the observation period, 2 deteriorated. DISCUSSION:
      The absence of a significant increase in fine motor disturbances proves, on the
      one hand, the efficacy of the therapy regime applied. On the other hand, the end
      point of a possible reversibility had been reached. A computer-aided analysis of
      the patient's handwriting allows for a sensitive detection of the "functional
      scar" in the extrapyramidal control and can subsequently prompt a timely
      correction of therapy in case of progression.

PMID- 20151007
TI  - Urodynamic profile in myelopathies: A follow-up study.
AB  - AIMS: To study the significance of filling cystometry in assessment and
      management of neurogenic bladder in myelopathies and correlate neurological
      recovery and bladder management in the follow up. STUDY DESIGN: Retrospective
      analysis of reports of filling cystometry in patients with traumatic and non
      traumatic myelopathy. SETTING: Neuro-rehabilitation unit of a tertiary care
      university hospital. METHODS: The study was carried out between September 2005
      and June 2006 and included all subjects with myelopathy who underwent filling
      cystometry. ASIA impairment scale was used to assess neurological status during
      admission as well as in the follow up. Bladder management was advised based on
      the cystometric findings. Neurological recovery and mode of bladder management
      were correlated during the follow up after a minimum of 6 months. RESULTS: Fifty
      two subjects (38 males, 14 females), mean age 33.26 +/- 14.66 years (10-80)
      underwent filling cystometry. Twenty patients had cervical, 24 had thoracic and 8
      had lumbar myelopathy. Cystometric findings were overactive detrusor observed in
      43 patients, (21 had detrusor sphincter dyssynergia (DSD), 22 without DSD) and
      areflexic/underactive detrusor in 9. Post-void residual (>15% of voided urine)
      was significant in 27 patients. Twenty-three patients (44%) reported for follow
      up (16 males, 7 females) after a mean duration of 9.04 +/- 2.44 months (6-15
      months). Neurological recovery was seen in 61% cases, while 1 patient showed
      deterioration. Only 26% patients reported change in bladder management during
      follow up. Correlation between neurological recovery and bladder management was
      found to be insignificant (P > 0.05) using spearman correlation co-efficient.
      CONCLUSIONS: Filling cystometry is valuable for assessment and management of
      neurogenic bladder after myelopathy. No significant relationship was observed
      between neurological recovery and neurogenic bladder management in the follow up
      in the present study.

PMID- 20151009
TI  - A basket full!

PMID- 20151008
TI  - An unusual cause of adult onset cerebellar ataxia with hypogonadism.
AB  - We report an unusual case of sporadic adult onset cerebellar ataxia with
      hypogonadism. A 40-year-old unmarried man presented with progressive ataxia and
      dysarthria along with complaints of non-development of secondary sexual
      characteristics and erectile dysfunction. There were complaints of intermittent
      diarrhea. Clinical examination revealed a pan-cerebellar syndrome with features
      of hypoandrogenism. No eye movement abnormalities were evident. There were signs
      of malabsorption. Investigations confirmed the presence of auto-antibodies found
      in celiac disease, and a duodenal biopsy confirmed the same. Hypoandrogenism was
      postulated to be due to hypergonadotropic hypogonadism which has been mentioned
      in a few patients of celiac disease. However, the pattern seen in our patient was
      of a hypogonadotropic hypogonadism. This is probably secondary to an autoimmune
      hypophysitis seen in some patients in the absence of other clinical
      manifestations. Autoantibody testing should be a diagnostic necessity in any
      adult with a sporadic cerebellar ataxia.

PMID- 20151010
TI  - Dermatomyositis presenting with rhabdomyolysis and acute renal failure; an
      uncommon manifestation.
AB  - Rhabdomyolysis and myoglobinuria are a rare complication of dermatomyositis. Such
      patient can land up in acute renal failure. Recognition of this fact has
      important therapeutic implications as patients require immunotherapy in addition
      to the symptomatic treatment for renal failure. We report a case of
      dermatomyositis with evidence of rhabdomyolysis and myoglobinuria presenting with
      acute renal failure. The patient responded dramatically to corticosteroid
      therapy.

PMID- 20151011
TI  - Heidenhain variant of Creutzfeldt-Jakob disease: An autopsy study from India.
AB  - Prion diseases are rare, progressive and fatal neurodegenerative diseases
      characterized by long incubation period and short clinical course. We present a
      rare case of Heidenhain variant of Creutzfeldt-Jakob disease, occurring in a 55
      year-old lady presenting with dementia, cortical blindness, and myoclonic jerks.
      She succumbed to the disease within 8 weeks of onset of symptoms. MRI revealed
      hyperintense signals on T2WI and fluid attenuated inversion recovery (FLAIR)
      images in basal ganglia and fronto-temporal and parietal cortex, sparing
      thalamus, striate cortex and globus pallidum. Abundant abnormal prion protein
      deposits (PrP(sc)) were detected in caudate, putamen, thalamus, cingulate and
      striate cortex, in comparison to frontal and parietal cortex while no deposits
      were found in globus pallidum. MRI changes did not correlate with degree of
      spongy change, gliosis or prion protein deposition. The cause for abnormal signal
      changes in MRI and FLAIR images remains unclear.

PMID- 20151012
TI  - The flaccid life.

PMID- 20151013
TI  - Creutzfeldt-Jakob disease: Importance of early magnetic resonance imaging.

PMID- 20151014
TI  - Pituitary apoplexy in a pregnant woman.

PMID- 20151015
TI  - Hereditary spastic paraplegia with thin corpus callosum.

PMID- 20151017
TI  - Minimising disability in stroke survivors.

PMID- 20151016
TI  - Technical standards for recording and interpretation of neonatal
      electroencephalogram in clinical practice.
AB  - Neonatal electroencephalogram (EEG), though often perceived as being difficult to
      record and interpret, is relatively easy to study due to the immature nature of
      the brain, which expresses only a few well-defined set of patterns. The EEG
      interpreter needs to be aware of the maturational changes as well as the effect
      of pathological processes and medication on brain activity. It gives valuable
      information for the treatment and prognostication in encephalopathic neonates. In
      this group, serial EEGs or EEG monitoring often gives additional information
      regarding deterioration/improvement of the brain function or occurrence of
      seizures.

PMID- 20151018
TI  - Diagnostic dilemma: Altered sensorium while taking hot water bath.

PMID- 20151019
TI  - Author's reply.

PMID- 20151020
TI  - New insights into the molecular pathogenesis of colorectal cancer.
AB  - Although there have been tremendous advances in the management of colorectal
      cancer (CRC), there is still a need for improved therapeutic approaches. On a
      molecular genetic level, CRC is one of the best-understood solid malignancies,
      and these insights can serve as a foundation for the design of novel targeted
      therapies. We present new genetic and epigenetic pathways that highlight the
      heterogeneous mechanisms in CRC pathogenesis, including the roles of the MYH DNA
      repair gene and of aberrant DNA hypermethylation and imprinting. We then describe
      some of the successful targeted therapies that inhibit COX2, EGFR, and VEGF as
      well as potential new targets that have been revealed by studies of molecular
      genetics.

PMID- 20151021
TI  - Photon-Counting H33D Detector for Biological Fluorescence Imaging.
AB  - We have developed a photon-counting High-temporal and High-spatial resolution,
      High-throughput 3-Dimensional detector (H33D) for biological imaging of
      fluorescent samples. The design is based on a 25 mm diameter S20 photocathode
      followed by a 3-microchannel plate stack, and a cross delay line anode. We
      describe the bench performance of the H33D detector, as well as preliminary
      imaging results obtained with fluorescent beads, quantum dots and live cells and
      discuss applications of future generation detectors for single-molecule imaging
      and high-throughput study of biomolecular interactions.

PMID- 20151022
TI  - A Stereodivergent Approach for Accessing Both C2,8a-Syn and C2,8a-Anti Relative
      Stereochemical Manifolds in the Lepadin Family via a TiCL(4)-Promoted Aza-[3 + 3]
      Annulation.
AB  - Details in developing a stereodivergent approach to the lepadin family and
      establishing an entry to both C2,8a-syn and C2,8a-anti relative stereochemical
      manifolds through a common intermediate are described here. This works paves a
      foundation for constructing all members of the lepadin family, which consists of
      three subsets based on an array of interesting relative configurations. These
      efforts underline the prominence of aza-[3 + 3] annulation as a unified strategy
      in alkaloid synthesis.

PMID- 20151023
TI  - FAST MONTE CARLO SIMULATION METHODS FOR BIOLOGICAL REACTION-DIFFUSION SYSTEMS IN
      SOLUTION AND ON SURFACES.
AB  - Many important physiological processes operate at time and space scales far
      beyond those accessible to atom-realistic simulations, and yet discrete
      stochastic rather than continuum methods may best represent finite numbers of
      molecules interacting in complex cellular spaces. We describe and validate new
      tools and algorithms developed for a new version of the MCell simulation program
      (MCell3), which supports generalized Monte Carlo modeling of diffusion and
      chemical reaction in solution, on surfaces representing membranes, and
      combinations thereof. A new syntax for describing the spatial directionality of
      surface reactions is introduced, along with optimizations and algorithms that can
      substantially reduce computational costs (e.g., event scheduling, variable time
      and space steps). Examples for simple reactions in simple spaces are validated by
      comparison to analytic solutions. Thus we show how spatially realistic Monte
      Carlo simulations of biological systems can be far more cost-effective than often
      is assumed, and provide a level of accuracy and insight beyond that of continuum
      methods.

PMID- 20151024
TI  - NF-kappaB signaling.
AB  - The NF-kappaB transcription factor is a critical regulator of the immune system,
      and is responsive to a large number of stimuli. Different stimuli engage
      signaling pathways to activate NF-kappaB, and effect distinct cellular responses.
      Mathematical modeling of the NF-kappaB network has been useful in studying the
      dynamic and cross-talk regulation of NF-kappaB. In this review, we discuss the
      regulation of NF-kappaB activity in response to different types of stimuli,
      including inflammatory signals, developmental cues, metabolic stress, and DNA
      damage. The distinct molecular mechanisms engaged in each pathway for activating
      and terminating NF-kappaB activity are discussed. In addition, we summarize the
      evidence for cross-talk mechanisms that allow for different stimuli to be
      integrated within the NF-kappaB signaling module to produce synergistic or
      qualitatively different signaling outcomes.

PMID- 20151025
TI  - Rescue of developmental defects by blastocyst stem cell injection: towards
      elucidation of neomorphic corrective pathways.
AB  - Stem cell-based therapy is an exciting area of high potential for regenerative
      medicine. To study disease prevention, we inject mouse embryonic stem cells
      (ESCs) into a variety of mouse blastocysts, most of which harbor mutations. Mice
      derived from these mutant blastocysts develop human-like diseases, either at
      developmental stages or in the adult, but blastocyst injection of ESCs prevents
      disease from occurring. Rather than entirely repopulating the affected organs,
      with just 20% of chimerism, the ESCs replenish protein levels that are absent in
      mutant mice, and induce novel or "neomorphic" signals that help circumvent the
      requirements for the mutations. We also show data indicating that the
      "neomorphic" mechanisms arise as a result of blastocyst injection of ESCs,
      regardless of the nature of the host blastocyst (mutant or wild-type). Thus,
      blastocyst injection of ESCs not only allows the study of disease prevention, but
      also unveils novel pathways whose activation may aid in the correction of
      congenital or acquired disease.

PMID- 20151026
TI  - Variable phenotypic expression of a MECP2 mutation in a family.
AB  - We report a three generation family in which five members, three females and two
      males, demonstrate a 44 bp deletion (1164-1207del44) in the MECP2 gene associated
      with Rett syndrome, leading to a truncation of the C-terminus of the protein. Two
      of the three females and both males do not meet RTT criteria whereas the youngest
      female has classic RTT. Both males demonstrated a clear pattern of progressive
      involvement including dystonia. The transmitting females do not demonstrate
      features of RTT as a result of unbalanced X chromosome inactivation (XCI) and
      were only identified as carriers following the evaluation of the affected males
      and the girl with classic RTT. As such, accurate assessment of the precise
      frequency of MECP2 mutations in carrier females with mild cognitive impairment or
      borderline cognitive function will be under-represented unless an affected
      offspring is recognized. Strategies for accurate diagnosis in such instances
      should be considered carefully.

PMID- 20151028
TI  - Multi-level control of ionotropic glutamate receptor function.
AB  - Because ionotropic glutamate receptors play critical roles in numerous CNS
      functions, there has been considerable interest in understanding molecular
      mechanisms regulating their properties. In particular, the search for ligands and
      corresponding binding sites providing allosteric regulation of agonist binding
      and channel opening and closing has been intensely pursued in the hope of
      developing new approaches for the treatment of a variety of CNS diseases
      associated with abnormal functioning of glutamatergic systems. Several recent
      publications have reported detailed structures of the N-terminal domains of NMDA
      and AMPA receptors and have generated interesting predictions regarding the
      possibility of finding new ways to control glutamate receptor function. Together
      with the recently reported control of the receptors by transmembrane proteins,
      there is now a whole set of potential regulators of these important families of
      receptors.

PMID- 20151029
TI  - Initial neuromuscular performance in older women influences response to explosive
      resistance training.
AB  - The purpose of the study was to identify both demographic and neuromuscular
      traits that characterize successful or unsuccessful adaptation to resistance
      training in older women. Twelve, older women underwent electrically evoked muscle
      twitches for the knee extensors; and performed maximal, voluntary, isometric knee
      extensions, followed by eight weeks of resistance training. Prior to training
      nonresponders had 67% higher twitch peak torque than responders (0.29 +/- 0.05
      vs. 0.18 +/- 0.06 Nm.kg(-1) respectively), 64% higher twitch rate of torque
      development (RTD) (3.96 +/- 0.47 vs. 2.42 +/- 0.62 Nm.s(-1).kg(-1)), 51% higher
      voluntary peak torque (1.86 +/- 0.40 vs. 1.23 +/- 0.33 Nm.kg(-1)), 101% greater
      RTD (9.43 +/- 1.52 vs. 4.70 +/- 2.40 Nm.s(-1).kg(-1)), 86% greater impulse (0.13
      +/- 0.01 vs. 0.07 +/- 0.03 Nm.s.kg(-1)) and 27% faster motor time (80 +/- 13 vs.
      109 +/- 34 ms), (all P < 0.05). Following training, responders showed an 11%
      increase in twitch peak torque over baseline (0.18 +/- 0.06 to 0.20 +/- 0.05
      Nm.kg(-1)), 15% increase in voluntary peak torque (1.23 +/- 0.33 to 1.41 +/- 0.36
      Nm.kg(-1)), 47% increase in RTD (4.70 +/- 2.40 to 6.93 +/- 2.02 Nm.s(-1).kg(-1)),
      43% increase in impulse (0.07 +/- 0.03 to 0.10 +/- 0.04 Nm.s.kg(-1)), and 26%
      increase in rate of EMG rise (886 +/- 214 to 1116 +/- 102 % pEMG.s(-1)) (all P <
      0.05). Initially higher muscle mass and contractility, coupled with greater
      neural drive, likely explains why older women with good muscle performance seem
      to have a lower capacity for improvement than women with low initial levels of
      performance.

PMID- 20151027
TI  - The Natural Selection of Herpesviruses and Virus-Specific NK Cell Receptors.
AB  - During the co-evolution of cytomegalovirus (CMV) and natural killer (NK) cells,
      each has evolved specific tactics in an attempt to prevail. CMV has evolved
      multiple immune evasion mechanisms to avoid detection by NK cells and other
      immune cells, leading to chronic infection. Meanwhile, the host has evolved virus
      specific receptors to counter these evasion strategies. The natural selection of
      viral genes and host receptors allows us to observe a unique molecular example of
      "survival of the fittest", as virus and immune cells try to out-maneuver one
      another or for the virus to achieve detente for optimal dissemination in the
      population.

PMID- 20151030
TI  - Assignment of Pre-edge Features in the Ru K-edge X-ray Absorption Spectra of
      Organometallic Ruthenium Complexes.
AB  - The nature of the lowest energy bound-state transition in the Ru K-edge X-ray
      Absorption Spectra for a series of Grubbs-type ruthenium complexes was
      investigated. The pre-edge feature was unambiguously assigned as resulting from
      formally electric dipole forbidden Ru 4d<--1s transitions. The intensities of
      these transitions are extremely sensitive to the ligand environment and the
      symmetry of the metal centre. In centrosymmetric complexes the pre-edge is very
      weak since it is limited by the weak electric quadrupole intensity mechanism. By
      contrast, upon breaking centrosymmetry, Ru 5p-4d mixing allows for introduction
      of electric dipole allowed character resulting in a dramatic increase in the pre
      edge intensity. The information content of this approach is explored as it
      relates to complexes of importance in olefin metathesis and its relevance as a
      tool for the study of reactive intermediates.

PMID- 20151031
TI  - A Pilot Study of Microbial Contamination of Subtropical Recreational Waters.
AB  - Microbial water quality indicators are used to determine whether a water body is
      safe for recreational purposes. There have been concerns raised about the
      appropriate use of microbial indicators to regulate recreational uses of water
      bodies, in particular those located in tropical and sub-tropical environments.
      This prospective cohort pilot study evaluated the relationship between microbial
      water quality indicators and public health within two public beaches without
      known sewage discharge, but with historically high microbial levels for one
      beach, in subtropical Miami-Dade County (Florida). Monitoring was conducted in
      three phases: daily water monitoring, beach sand sampling, and spatially intense
      water sampling. An epidemiological questionnaire from a Los Angeles recreational
      beach-goer study was used to assess the self-reported swimming-related symptoms
      and exposures. There was no significant association between the number nor the
      type of reported symptoms and the different sampling months or beach sites,
      although persons who returned repeatedly to the beach were more likely to report
      symptoms. The number of indicator organisms correlated negatively with the
      frequency of symptoms reported by recreational beach goers. Results of the daily
      monitoring indicated that different indicators provided conflicting results
      concerning beach water quality.Larger epidemiologic studies with individual
      exposure monitoring are recommended to further evaluate these potentially
      important associations in subtropical recreational waters.

PMID- 20151033
TI  - Families by Adoption and Birth: II. Mother-Infant Cognitive Interactions.
AB  - Adopted children are more likely to develop learning and school adjustment
      problems than are their non-adopted peers, despite the fact that learning
      potential appears to be comparable in the two groups. In an effort to explain
      this phenomenon, the present study examined cognitive behavior repertoires in
      healthy 5-month-old first infants and their mothers during their normal daily
      routine in families by adoption and by birth. Two areas of functioning,
      vocal/verbal communication and exploration, were examined. Infants and mothers in
      both groups were similar in the frequency and ranking of a full array of age
      appropriate cognitive behaviors. Both groups of babies experienced rich and
      comparable opportunities for the development of language competence. In the
      exploratory realm, group differences emerged for some infant measures; infants by
      birth were in an alert state and mouthed objects more than infants by adoption.
      Examination of the linkages among infant behaviors and between mothers and
      infants suggested that, while mothers by birth and adoption provided comparable
      opportunities for exploration, infants by birth were engaging in exploratory
      behavior to a somewhat greater extent.

PMID- 20151034
TI  - Learning and liking an artificial musical system: Effects of set size and
      repeated exposure.
AB  - We report an investigation of humans' musical learning ability using a novel
      musical system. We designed an artificial musical system based on the Bohlen
      Pierce scale, a scale very different from Western music. Melodies were composed
      from chord progressions in the new scale by applying the rules of a finite-state
      grammar. After exposing participants to sets of melodies, we conducted listening
      tests to assess learning, including recognition tests, generalization tests, and
      subjective preference ratings. In Experiment 1, participants were presented with
      15 melodies 27 times each. Forced choice results showed that participants were
      able to recognize previously encountered melodies and generalize their knowledge
      to new melodies, suggesting internalization of the musical grammar.Preference
      ratings showed no differentiation among familiar, new, and ungrammatical
      melodies. In Experiment 2, participants were given 10 melodies 40 times each.
      Results showed superior recognition but unsuccessful generalization.
      Additionally, preference ratings were significantly higher for familiar melodies.
      Results from the two experiments suggest that humans can internalize the
      grammatical structure of a new musical system following exposure to a
      sufficiently large set size of melodies, but musical preference results from
      repeated exposure to a small number of items. This dissociation between grammar
      learning and preference will be further discussed.

PMID- 20151035
TI  - Recent advances that favor development of a vaccine for Helicobacter pylori
      infection.

PMID- 20151032
TI  - Current and future approaches for control of graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD), both acute and chronic, remains one of the
      major barriers to improving outcomes after allogeneic stem cell transplantation.
      The pathophysiology of GVHD is complex and incompletely understood. GVHD is
      believed to arise from the interaction of: tissue damage and proinflammatory
      cytokines causing activation of antigen-presenting cells (APCs, donor T-cell
      activation by APCs and cytokines and host tissue injury by effector T lymphocytes
      and proinflammatory cytokines. There is also a role for additional lymphocyte
      subtypes (naive and memory T cells, regulatory T cells, natural killer T cells
      and B cells) in GVHD pathogenesis. Strategies to improve donor-recipient HLA
      match, and to minimize conditioning toxicity, cytokine release and APC and
      effector T-lymphocyte activation, will likely improve prophylaxis of acute (and
      possibly chronic) GVHD. Therapy of established acute and chronic GVHD is still
      heavily dependent on corticosteroids, despite their limited efficacy and
      considerable toxicity. Novel agents (and/or combinations of agents) comprising
      pharmacologic, biologic and cellular therapies targeting specific steps or
      subsets involved in immune activation will likely comprise future advances in
      GVHD control. This article reviews the current state of knowledge regarding the
      prevention and treatment of acute and chronic GVHD. Novel approaches currently
      undergoing evaluation are also highlighted.

PMID- 20151036
TI  - Joint modeling of self-rated health and changes in physical functioning.
AB  - Self-rated health is an important indicator of future morbidity and mortality.
      Past research has indicated that self-rated health is related to both levels of
      and changes in physical functioning. However, no previous study has jointly
      modeled longitudinal functional status and self-rated health trajectories. We
      propose a joint model for self-rated health and physical functioning that
      describes the relationship between perceptions of health and the rate of change
      of physical functioning or disability. Our joint model uses a non-homogeneous
      Markov process for discrete physical functioning states and connects this to a
      logistic regression model for "healthy" versus "unhealthy" self-rated health
      through parameters of the physical functioning model. We use simulation studies
      to establish finite sample properties of our estimators and show that this model
      is robust to misspecification of the functional form of the relationship between
      self-rated health and rate of change of physical functioning. We also show that
      our joint model performs better than an empirical model based on observed changes
      in functional status. We apply our joint model to data from the Cardiovascular
      Health Study (CHS), a large, multi-center, longitudinal study of older adults.
      Our analysis indicates that self-rated health is associated both with level of
      functioning as indicated by difficulty with activities of daily living (ADL) and
      instrumental activities of daily living (IADL), and the risk of increasing
      difficulty with ADLs and IADLs.

PMID- 20151037
TI  - ASYMMETRIC SYNTHESIS OF THE ABCD RING SYSTEM OF DAPHNILACTONE B VIA A TANDEM,
      DOUBLE INTRAMOLECULAR, [4+2]/[3+2] CYCLOADDITION STRATEGY.
AB  - An asymmetric synthesis of the ABCD ring system of daphnilactone B is described.
      The synthesis features a tandem, double intramolecular, [4+2]/[3+2] cycloaddition
      of a highly functionalized, enantiomerically enriched nitroalkene to generate a
      pentacyclic nitroso acetal. The cycloaddition establishes six contiguous
      stereogenic centers including the critical CD ring junction that bears two
      quaternary stereogenic centers. Hydrogenolysis of the nitroso acetal followed by
      amide reduction and cyclization provided the AB rings. The methyl substituent on
      the A ring was installed in the correct configuration via hydrogenation of an
      exocyclic olefin in the final step.

PMID- 20151038
TI  - In Vitro Electrochemistry of Biological Systems.
AB  - This article reviews recent work involving electrochemical methods for in vitro
      analysis of biomolecules, with an emphasis on detection and manipulation at and
      of single cells and cultures of cells. The techniques discussed include constant
      potential amperometry, chronoamperometry, cellular electroporation, scanning
      electrochemical microscopy, and microfluidic platforms integrated with
      electrochemical detection. The principles of these methods are briefly described,
      followed in most cases with a short description of an analytical or biological
      application and its significance. The use of electrochemical methods to examine
      specific mechanistic issues in exocytosis is highlighted, as a great deal of
      recent work has been devoted to this application.

PMID- 20151040
TI  - Phospho-Site-Specific Antibody Microarray to Study the State of Protein
      Phosphorylation in the Retina.
AB  - Neurodegeneration is an important component of diabetic retinopathy as
      demonstrated by increased neural apoptosis in the retina during experimental and
      human diabetes. Accumulation of sorbitol and fructose and the generation or
      enhancement of oxidative stress has been reported in the whole retina of diabetic
      animals. Aldose reductase (AR), the first and the rate limiting enzyme in the
      pathway reduces glucose to sorbitol and the diabetic complications are prevented
      by drugs that inhibit AR. In this study we examined the phosphorylation state of
      various retinal proteins in response to sorbitol-treatment by phosphor-site
      specific antibody microarray. Our results suggest that various retinal protein
      kinases and cytoskeletal proteins either activated or down regulated in response
      to sorbitol treatment. Further, our study also indicates the activation of
      retinal insulin- and insulin growth factor 1 receptor and their downstream
      signaling proteins such as phosphoinositide 3-kinanse and protein kinase B (Akt).
      Understanding the regulation of retinal proteins involved in polyol (sorbitol)
      pathway would help to design therapeutic agents for the treatment of diabetic
      retinopathy.

PMID- 20151039
TI  - Management of High-Throughput DNA Sequencing Projects: Alpheus.
AB  - High-throughput DNA sequencing has enabled systems biology to begin to address
      areas in health, agricultural and basic biological research. Concomitant with the
      opportunities is an absolute necessity to manage significant volumes of high
      dimensional and inter-related data and analysis. Alpheus is an analysis pipeline,
      database and visualization software for use with massively parallel DNA
      sequencing technologies that feature multi-gigabase throughput characterized by
      relatively short reads, such as Illumina-Solexa (sequencing-by-synthesis), Roche
      454 (pyrosequencing) and Applied Biosystem's SOLiD (sequencing-by-ligation).
      Alpheus enables alignment to reference sequence(s), detection of variants and
      enumeration of sequence abundance, including expression levels in transcriptome
      sequence. Alpheus is able to detect several types of variants, including non
      synonymous and synonymous single nucleotide polymorphisms (SNPs),
      insertions/deletions (indels), premature stop codons, and splice isoforms.
      Variant detection is aided by the ability to filter variant calls based on
      consistency, expected allele frequency, sequence quality, coverage, and variant
      type in order to minimize false positives while maximizing the identification of
      true positives. Alpheus also enables comparisons of genes with variants between
      cases and controls or bulk segregant pools. Sequence-based differential
      expression comparisons can be developed, with data export to SAS JMP Genomics for
      statistical analysis.

PMID- 20151041
TI  - Quality Weighted Mean and T-test in Microarray Analysis Lead to Improved Accuracy
      in Gene Expression Measurements and Reduced Type I and II Errors in Differential
      Expression Detection.
AB  - Previously we have reported a microarray image processing and data analysis
      package Matarray, where quality scores are defined for every spot that reflect
      the reliability and variability of the data acquired from each spot. In this
      article we present a new development in Matarray, where the quality scores are
      incorporated as weights in the statistical evaluation and data mining of
      microarray data. With this approach filtering of poor quality data is
      automatically achieved through the reduction in their weights, thereby
      eliminating the need to manually flag or remove bad data points, as well as the
      problem of missing values. More significantly, utilizing a set of control clones
      spiked in at known input ratios ranging from 1:30 to 30:1, we find that the
      quality-weighted statistics leads to more accurate gene expression measurements
      and more sensitive detection of their changes with significantly lower type II
      error rates. Further, we have applied the quality-weighted clustering to a time
      course microarray data set, and find that the new algorithm improves grouping
      accuracy. In summary, incorporating quantitative quality measure of microarray
      data as weight in complex data analysis leads to improved reliability and
      convenience. In addition it provides a practical way to deal with the missing
      value issue in establishing automatic statistical tests.

PMID- 20151042
TI  - Candesartan Differentially Regulates Epithelial Sodium Channel in Cortex Versus
      Medulla of Streptozotocin-Induced Diabetic Rats.
AB  - Diabetes is associated with an activated renal renin-angiotensin-aldosterone
      system (RAAS) and it was shown that streptozotocin (STZ)-induced diabetic rats
      had increased whole kidney protein levels of the epithelial sodium channel
      subunits (alpha-, beta- and gamma-ENaC). However, the role of the RAAS on the
      regional, i.e., cortical versus medullary, regulation of ENaC is unclear. Male
      Sprague-Dawley rats were injected with STZ (intravenous, 65 mg/kg.bw,
      n=12/group). After 14 days, half of them received drinking water with candesartan
      (2 mg/kg.bw/day), an angiotensin-II type-1 receptor (AT1R) antagonist, for one
      week. In the medulla, i.e., inner stripe of the outer medulla (ISOM), base and/or
      tip of the inner medulla, immunoblotting revealed increased protein abundances of
      alpha1 Na-K-ATPase and ENaC subunits with diabetes (200-600% of controls), which
      were not reversed by candesartan. In fact, candesartan increased all ENaC
      subunits and alpha1 Na-K-ATPase in the ISOM and/or base in control rats. In
      contrast, in the cortex, diabetes did not increase these proteins. However,
      candesartan reduced cortical beta- and gamma-ENaC regardless of diabetic state.
      In summary, diabetes-induced increases in ENaC were seen preferentially in the
      medulla. These changes appeared to be due to a mechanism clearly distinct from
      AT1R activation, because they were not abolished by candesartan. In fact,
      candesartan treatment tended to increase some of these medullary proteins,
      perhaps in compensation for increased NaCl load. In contrast, cortical beta- and
      gamma-ENaC were reduced by candesartan regardless of diabetic state suggesting
      their regulation by AT1R at this site; however this did not appear to be a site
      of diabetes-induced ENaC up-regulation.

PMID- 20151043
TI  - Does Typography of Substance Abuse and Dependence Differ as a Function of
      Exposure to Child Maltreatment?
AB  - We investigated the link between child maltreatment, including child sexual
      assault (CSA) and child physical assault (CPA), and addiction-related
      symptomatology in a subsample of adolescents from the National Survey of
      Adolescents, all of whom met DSM-IV criteria for substance abuse or dependence
      (n=281). Over 60% of the sample reported a history of CSA and/or CPA. Results
      indicated significant differences in typography of substance abuse and dependence
      symptoms and rates of comorbid lifetime PTSD based on assault history, specific
      assault incident characteristics, and sex. Clinical implications for substance
      abusing youth with maltreatment histories are discussed.

PMID- 20151044
TI  - Single-Molecule Studies on Fluorescently Labeled Silver Particles: Effects of
      Particle Size.
AB  - We studied the dependence of single-molecule fluorescence on the size of nearby
      metal particles. The silver particles were synthesized with average diameters of
      metal cores being 5, 20, 50, 70, and 100 nm, respectively. A single-stranded
      oligonucleotide was chemically bound to a single silver particle and a Cy5
      labeled complementary single-stranded oligonucleotide was hybridized with the
      particle-bound oligonucleotide. The space between the fluorophore and metal core
      was separated by a rigid hybridized DNA duplex of 8 nm length. The single
      fluorescence images and intensity traces were recorded by scanning confocal
      microscopy. The single fluorophore-labeled 50 nm silver particles displayed the
      most enhanced intensity, a factor of 17-fold increase relative to the free
      fluorophores in the absence of metal. Numerical simulations by the finite
      difference time-domain (FDTD) method and results from Mie theory were used to
      compare with the experimental results. The 50 nm silver particles were also
      labeled by multiple fluorophores. The fluorescence intensity of multiple
      fluorophore-labeled metal particles increases dramatically with the loading
      number and reached 400-fold relative to the free single fluorophore when the
      loading number of fluorophore per metal particle was 50. The fluorophore also
      displayed better photostability when binding on the metal particle. These results
      can aid us to develop novel nanoscale fluorophores for clinical diagnostics and
      bioassay.

PMID- 20151045
TI  - Beyond the HapMap Genotypic Data: Prospects of Deep Resequencing Projects.
AB  - The International HapMap Project provides a key resource of genotypic data on
      human samples including lymphoblastoid cell lines derived from individuals of
      four major world populations of African, European, Japanese and Chinese ancestry.
      Researchers have utilized this resource to identify genetic elements that
      correlate with various phenotypes such as risks of common diseases, individual
      drug response and gene expression variation. However, recent comparative studies
      have suggested that the currently available HapMap genotypic data may not capture
      a substantial proportion of rare or untyped SNPs in these populations, implying
      that the HapMap SNPs may not be sufficient for comprehensive association studies.
      In this paper, three large-scale deep resequencing projects covering the HapMap
      samples: ENCODE (Encyclopedia of DNA Elements), SeattleSNPs and NIEHS (National
      Institute of Environmental Health Sciences) Environmental Genome Project are
      discussed. Prospectively, once integrated with the HapMap resource, these efforts
      will greatly benefit the next wave of association studies and data mining using
      these cell lines.

PMID- 20151046
TI  - Single Molecule Probing of Exocytotic Protein Interactions Using Force
      Spectroscopy.
AB  - Relatively recently, the Atomic Force Microscope (AFM) emerged as a powerful tool
      for single molecule nanomechanical investigations. Parameters that can be
      measured by force spectroscopy using AFM, such as the force and total mechanical
      extension required to break bonds between various proteins can yield valuable
      insights into the nature of the bond (zippering vs. highly localized binding
      site), the sequence of its interactions and the energy landscape along the length
      of the interaction. In this review we discuss the use of AFM in force
      spectroscopy mode to study intermolecular interactions between the exocytotic
      proteins of the core SNARE complex. Information gathered by force spectroscopy of
      protein-protein interactions of this complex supplement previous results acquired
      with other techniques, and allows a deeper understanding of SNARE protein
      interactions and their role in exocytosis.

PMID- 20151047
TI  - Classifiers as Count Syntax: Individuation and Measurement in the Acquisition of
      Mandarin Chinese.
AB  - The distinction between mass nouns (e.g., butter) and count nouns (e.g., table)
      offers a test case for asking how the syntax and semantics of natural language
      are related, and how children exploit syntax-semantics mappings when acquiring
      language. Virtually no studies have examined this distinction in classifier
      languages (e.g., Mandarin Chinese) due to the widespread assumption that such
      languages lack mass-count syntax. However, Cheng and Sybesma (1998) argue that
      Mandarin encodes the mass-count at the classifier level: classifiers can be
      categorized as "mass-classifiers" or "count-classifiers." Mass and count
      classifiers differ in semantic interpretation and occur in different syntactic
      constructions. The current study is first an empirical test of Cheng and
      Sybesma's hypothesis, and second, a test of the acquisition of putative mass and
      count classifiers by children learning Mandarin. Experiments 1 and 2 asked
      whether count-classifiers select individuals and mass classifiers select
      nonindividuals and sets of individuals. Adult Mandarin-speakers indeed showed
      this pattern of interpretation, while 4- to 6-year-olds had not fully mastered
      the distinction. Experiment 3 tested participants' syntactic sensitivity by
      asking them to match two syntactic constructions (one that supported the mass or
      portion reading and one that did not) to two contrasting choices (a portion of an
      object and a whole object). A developmental trend was observed for the syntactic
      knowledge from 4-year-old children into adulthood: adults were near perfect and
      the older children were more likely than the younger children to correctly match
      the contrasting phrases to the objects. Thus, in three experiments we find
      support for Cheng and Sybesma's analysis, but also find that children master the
      syntax and semantics of Mandarin classifiers much later than English-speaking
      children acquire knowledge of the English mass-count distinction.

PMID- 20151048
TI  - Effect of dose-escalation of 5-fluorouracil on circadian variability of its
      pharmacokinetics in Japanese patients with Stage III/IVa esophageal squamous cell
      carcinoma.
AB  - OBJECTIVE: The effects of dose-escalation of 5-fluorouracil (5-FU) on the
      clinical outcome and pharmacokinetics of 5-FU were investigated in Japanese
      patients with Stage III/IVa esophageal squamous cell carcinoma. METHODS: Thirty
      five patients with Stage III/IVa were enrolled, who were treated with a
      definitive 5-FU/cisplatin-based chemoradiotherapy. A course consisted of
      continuous infusion of 5-FU at 400 mg/m(2)/day (the standard dose group, N=27) or
      500-550 mg/m(2)/day (the high dose group, N=8) for days 1-5 and 8-12, infusion of
      cisplatin at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1
      to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week
      interval. Plasma concentrations of 5-FU were determined by high performance
      liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days
      4, 11, 39 and 46. RESULTS AND CONCLUSIONS: No patient with Stage IVa achieved a
      complete response in the standard dose group, whereas a complete response was
      observed at a rate of 50% in the high dose group, and this can be explained by a
      higher plasma concentration of 5-FU. The circadian rhythm in the concentrations
      found at the standard dose was not observed for a higher dose.

PMID- 20151050
TI  - Member needs reassessment provides encouraging feedback and growth opportunities
      for the CCS.

PMID- 20151049
TI  - Comparative study of the binding pockets of mammalian proprotein convertases and
      its implications for the design of specific small molecule inhibitors.
AB  - Proprotein convertases are enzymes that proteolytically cleave protein precursors
      in the secretory pathway to yield functional proteins. Seven mammalian
      subtilisin/Kex2p-like proprotein convertases have been identified: furin, PC1,
      PC2, PC4, PACE4, PC5 and PC7. The binding pockets of all seven proprotein
      convertases are evolutionarily conserved and highly similar. Among the seven
      proprotein convertases, the furin cleavage site motif has recently been
      characterized as a 20-residue motif that includes one core region P6-P2' inside
      the furin binding pocket. This study extended this information by examining the
      3D structural environment of the furin binding pocket surrounding the core region
      P6-P2' of furin substrates. The physical properties of mutations in the binding
      pockets of the other six mammalian proprotein convertases were compared. The
      results suggest that: 1) mutations at two positions, Glu230 and Glu257, change
      the overall density of the negative charge of the binding pockets, and govern the
      substrate specificities of mammalian proprotein convertases; 2) two proprotein
      convertases (PC1 and PC2) may have reduced sensitivity for positively charged
      residues at substrate position P5 or P6, whereas the substrate specificities of
      three proprotein convertases (furin, PACE4, and PC5) are similar to each other.
      This finding led to a novel design of a short peptide pattern for small molecule
      inhibitors: [K/R]-X-V-X-K-R. Compared with the widely used small molecule dec
      RVKR-cmk that inhibits all seven proprotein convertases, a finely-tuned
      derivative of the short peptide pattern [K/R]-X-V-X-K-R may have the potential to
      more effectively inhibit five of the proprotein convertases (furin, PC4, PACE4,
      PC5 and PC7) compared to the remaining two (PC1 and PC2). The results not only
      provide insights into the molecular evolution of enzyme function in the
      proprotein convertase family, but will also aid the study of the functional
      redundancy of proprotein convertases and the development of therapeutic
      applications.

PMID- 20151051
TI  - Canadian Cardiovascular Society Access to Care Workshop proceedings and next
      steps.
AB  - On October 24, 2008, the Canadian Cardiovascular Society (CCS) Standing Committee
      on Access to Care invited clinical practitioners, researchers and administrators
      from across Canada to provide input on the CCS action plan for 2009/2010. The
      meeting provided an opportunity for stakeholders to identify initiatives under
      three CCS priority areas for action: collecting and reporting wait time data,
      improving systems to improve access, and establishing national networks. Building
      on the suggestions from this meeting, the Standing Committee drafted an action
      plan for 2009/2010. This plan includes a lead role for the CCS in facilitating
      consensus on pan-Canadian data standards and definitions, and using current
      resources and infrastructure. The CCS and its Standing Committee look forward to
      continuing to work with stakeholders to promote awareness and adoption of the
      benchmarks, and to undertake new initiatives that will provide insight into
      access to care issues along the continuum of care.

PMID- 20151052
TI  - The efficacy of smoking cessation therapies in cardiac patients: a meta-analysis
      of randomized controlled trials.
AB  - INTRODUCTION: Several meta-analyses have examined the efficacy of smoking
      cessation therapies in the general population. However, little is known about the
      efficacy of these therapies in cardiac patients. Therefore, a meta-analysis of
      randomized controlled trials (RCTs) was performed to determine the efficacy of
      behavioural therapy and pharmacotherapy for smoking cessation in cardiac
      patients. METHODS: The medical literature was systematically reviewed to identify
      smoking cessation RCTs in cardiac patients. Only RCTs that reported smoking
      abstinence at six or 12 months were included. Smoking abstinence was examined
      based on the 'most rigorous criterion', defined as the most conservative outcome
      reported in any given RCT. RESULTS: Eleven behavioural therapy RCTs that enrolled
      2105 patients and four pharmacotherapy RCTs that enrolled 1542 patients were
      identified. RCTs differed in the type of behavioural therapy administered as well
      as the total length and duration of the intervention. RCTs differed in the type
      of pharmacotherapy administered (one nicotine patch RCT, one nicotine gum RCT and
      two bupropion RCTs). Behavioural therapy was associated with a significantly
      higher proportion of smoking abstinence than usual care (OR 1.97 [95% CI 1.37 to
      2.85]). Pharmacotherapies were more efficacious than placebo (pooled OR 1.72 [95%
      CI 1.15 to 2.57]). CONCLUSIONS: Both behavioural therapy and pharmacotherapy are
      more efficacious than usual care for smoking cessation in cardiac patients. The
      present meta-analysis highlights the need for head-to-head RCTs to identify which
      smoking cessation therapy is preferred in cardiac patients as well as RCTs
      examining the efficacy of combined behavioural and pharmacotherapies.

PMID- 20151055
TI  - Mechanical assist and transplantation for treatment of giant cell myocarditis.
AB  - A case of Epstein-Barr virus-related acute giant cell myocarditis in a 16-year
      old boy is reported. Fulminant heart failure was successfully treated with
      extracorporeal membrane oxygenation as a bridge to urgent heart transplantation,
      and was again necessary after transplantation because of acute right heart
      failure. Clinical management and postoperative surveillance of this unusual
      problem are presented and discussed.

PMID- 20151054
TI  - The incretin system and cardiometabolic disease.
AB  - Rates of type 2 diabetes, obesity and their associated detrimental cardiovascular
      effects are rapidly increasing. Despite the availability of several treatment
      options for type 2 diabetes and the use of intensive regimens combining several
      antidiabetic drugs, less than one-half of all patients reach a target
      glycosylated hemoglobin level of less than 7%. Disease progression due to ongoing
      deterioration of pancreatic islet cell health and beta-cell function is likely
      responsible. Therefore, there is a need to identify new pharmacological compounds
      that may not only treat hyperglycemia, but may also correct impaired glucose
      homeostasis and preserve endogenous beta-cell function. Identification and
      characterization of the incretin system and its effect on glucose homeostasis
      have resulted in the development of new antidiabetic agents that target these
      concerns. The current review examines the incretin effect and the pharmacological
      agents that have been developed based on the understanding of this physiological
      system. The influence of incretins on the cardiovascular system beyond the
      proatherogenic effect of type 2 diabetes will also be discussed.

PMID- 20151053
TI  - Achieving cholesterol targets by individualizing starting doses of statin
      according to baseline low-density lipoprotein cholesterol and coronary artery
      disease risk category: the CANadians Achieve Cholesterol Targets Fast with
      Atorvastatin Stratified Titration (CanACTFAST) study.
AB  - BACKGROUND: Despite an increasing body of evidence on the benefit of lowering
      elevated levels of low-density lipoprotein cholesterol (LDL-C), there is still
      considerable concern that patients are not achieving target LDL-C levels.
      OBJECTIVE: The CANadians Achieve Cholesterol Targets Fast with Atorvastatin
      Stratified Titration (CanACTFAST) trial tested whether an algorithm-based statin
      dosing approach would enable patients to achieve LDL-C and total cholesterol/high
      density lipoprotein cholesterol (TC/HDL-C) ratio targets quickly. METHODS:
      Subjects requiring statin therapy, but with an LDL-C level of 5.7 mmol/L or
      lower, and triglycerides of 6.8 mmol/L or lower at screening participated in the
      12-week study, which had two open-label, six-week phases: a treatment period
      during which patients received 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin based
      on an algorithm incorporating baseline LDL-C value and cardiovascular risk; and
      patients who achieved both LDL-C and TC/HDL-C ratio targets at six weeks
      continued on the same atorvastatin dose. Patients who did not achieve both
      targets received dose uptitration using a single-step titration regimen. The
      primary efficacy outcome was the proportion of patients achieving target LDL-C
      levels after 12 weeks. RESULTS: Of 2016 subjects screened at 88 Canadian sites,
      1258 were assigned to a study drug (1101 were statin-free and 157 were statin
      treated at baseline). The proportion of subjects who achieved LDL-C targets after
      12 weeks of treatment was 86% (95% CI 84% to 88%) for statin-free patients and
      54% (95% CI 46% to 61%) for statin-treated patients. Overall, 1003 subjects (80%;
      95% CI 78% to 82%) achieved both lipid targets. CONCLUSIONS: Algorithm-based
      statin dosing enables patients to achieve LDL-C and TC/HDL-C ratio targets
      quickly, with either no titration or a single titration.

PMID- 20151056
TI  - Factors influencing the echocardiographic estimate of right ventricular systolic
      pressure in normal patients and clinically relevant ranges according to age.
AB  - BACKGROUND: Previous studies have shown that in the absence of underlying cardiac
      pathology, the echocardiographic estimate of right ventricular systolic pressure
      (RVSP) increases progressively and normally with age. There are limited data in
      patients older than 60 years of age. OBJECTIVE: To define the ranges of RVSP
      according to age and to include more elderly patients than have previously been
      reported. METHODS: All patients undergoing echocardiography since May 26, 1999,
      at the Kingston Heart Clinic (Kingston, Ontario) have had their data entered into
      a locally designed cardiology database (CARDIOfile; Registered trademark,
      Kingston Heart Clinic). RVSP was calculated from the peak tricuspid regurgitant
      jet velocity (V) using the modified Bernoulli equation (RVSP = 4V2 + RAP), with
      the mean right atrial pressure (RAP) estimated to be 10 mmHg. Of the 22,628
      patients who had undergone echocardiography, 10,905 had RVSP measured. All
      abnormal echocardiograms were excluded, leaving 1559 echocardiograms for
      analysis. RESULTS: Patient age ranged from 15 to 93 years. The mean age was 49
      years. RVSP increased significantly only after the age of 50 years. The mean (+/-
      SD) RVSP for those younger than 50 years, 50 to 75 years, and older than 75 years
      of age was 27.3+/-5.7 mmHg, 30.2+/-7.6 mmHg and 34.8+/-8.7 mmHg, respectively
      (P<0.0001 among all age groups). The normal range (95% CI) of RVSP in those
      younger than 50 years, 50 to 75 years, and older than 75 years of age was 16 mmHg
      to 39 mmHg, 15 mmHg to 45 mmHg, and 17 mmHg to 52 mmHg, respectively.
      Multivariate analysis indicated that age, mitral diastolic early-to-late filling
      velocity ratio, ejection fraction, aortic size and early mitral filling velocity/
      early diastolic mitral annular velocity were the only significant independent
      variables. There were significant changes in diastolic function with increasing
      age, which may have been responsible for the changes in RVSP. CONCLUSIONS: RVSP
      remains stable in both men and women until the age of 50 years. Thereafter, RVSP
      increases progressively in a linear manner with age and is significantly higher
      in patients older than 75 years of age. The changes may relate to changes in
      diastolic function. These ranges should be taken into account when using
      echocardiogram-derived RVSP for the diagnosis of pulmonary hypertension in the
      absence of cardiovascular disease.

PMID- 20151057
TI  - Long-term outcomes with paclitaxel-eluting stents versus bare metal stents in
      everyday practice: a Canadian experience.
AB  - BACKGROUND: In randomized trials, paclitaxel-eluting stents (PES) are superior to
      bare metal stents (BMS) in reducing target lesion revascularization (TLR).
      However, recent reports suggest there may be an increase in late stent thrombosis
      with long-term follow-up in PES-treated patients. METHODS: Prospectively
      collected data from a regional cardiac referral centre were analyzed to compare
      PES versus BMS in all consecutive patients undergoing percutaneous coronary
      intervention from April 2003 to March 2004. Outcomes included combined death,
      myocardial infarction and clinically driven TLR, as well as stent thrombosis at
      four years follow-up. RESULTS: A total of 512 patients were treated with PES and
      722 patients with BMS. At four years, there was 92% follow-up in both groups. The
      composite outcome of death, myocardial infarction and TLR was 13.9% in the PES
      group compared with 20% in the BMS group (P=0.01). This difference was primarily
      driven by the reduction in TLR in the PES cohort (3.9% versus 8%, P<0.01). The
      rate of definite stent thrombosis was 1.6% in the PES group compared with 0.4% in
      the BMS group (P=0.03). CONCLUSION: While PES offers an absolute 4.1% reduction
      in clinically driven TLR at four years, there is an associated increased risk of
      stent thrombosis. Further long-term studies addressing clinical outcomes
      including stent thrombosis with PES versus BMS are required to clarify this risk/
      benefit balance.

PMID- 20151058
TI  - Estimated right ventricular systolic pressure during exercise stress
      echocardiography in patients with suspected coronary artery disease.
AB  - OBJECTIVE: To determine the normal range of estimated right ventricular systolic
      pressure (RVSP) at peak exercise during exercise stress echocardiography (ExECHO)
      in a series of consecutive patients referred for the investigation of coronary
      artery disease. METHODS: Of 1057 ExECHO examinations over a span of 11 months,
      807 met the study criteria. A total of 250 patients were excluded, 188 for
      missing rest or peak RVSP measurements, 16 for a resting RVSP above 50 mmHg, 16
      for nondiagnostic echocardiographic images and the remaining 30 for missing data.
      The maximal tricuspid regurgitant jet was recorded at rest and following
      acquisition of the stress images (mean [+/- SD] time 103.1+/-35.2 s). A mean
      right atrial pressure of 10 mmHg was used in the calculation of RVSP. All data
      were entered into a cardiology database (CARDIOfile; Registered trademark,
      Kingston Heart Clinic) for later retrieval and analysis. RESULTS: There were 206
      male (58.9+/-12.0 years of age) and 601 female patients (57.4+/-12.0 years of
      age). Patient age ranged from 18 to 90 years. The mean resting and peak exercise
      RVSP was 27.8+/-7.8 mmHg and 34.8+/-11.3 mmHg in men, and 27.8+/-7.7 mmHg and
      34.6+/-11.7 mmHg in women, respectively. The mean increase in RVSP was 7.0+/-8.8
      mmHg in men and 6.7+/-8.9 mmHg in women. The 95% CI for peak RVSP was 12.2 mmHg
      to 57.4 mmHg in men, and 11.2 mmHg to 58.0 mmHg in women. There was no
      significant difference in peak RVSP for a normal ExECHO compared with an abnormal
      ExECHO. RVSP at rest and at peak exercise increased with both age and left atrial
      size. CONCLUSIONS: In individual patients, the RVSP should not increase above the
      resting value by more than 24.6 mmHg in men and 24.5 mmHg in women. This value
      was calculated as the increase in RVSP plus 2xSD of the RVSP. Peak RVSP should
      not exceed 57.4 mmHg in men and 58.0 mmHg in women. If either of these criteria
      is exceeded, the response of RVSP to exercise should be considered abnormal.

PMID- 20151059
TI  - Exposure to extreme cold lowers the ischemic threshold in coronary artery disease
      patients.
AB  - BACKGROUND: Cold temperature is known to commonly precipitate angina pectoris in
      patients with symptomatic coronary artery disease (CAD). It was previously shown
      that the ischemic threshold was lower during exercise testing at -8 degrees C
      than at +20 degrees C in patients with a history of cold-induced angina, whereas
      it was unchanged in patients without cold-induced angina. Few data exist on the
      impact of more severe cold exposure on myocardial ischemia. OBJECTIVE: To
      determine the effect of extreme cold exposure (-20 degrees C) on the ischemic
      threshold among CAD patients. METHODS: Thirteen men with CAD and documented
      exercise-induced ischemia performed two treadmill exercise tests, one at +20
      degrees C and one at -20 degrees C, in random order. Electrocardiograms were
      recorded every 30 s and analyzed separately in random order by two experienced
      readers blinded to temperature. RESULTS: The mean (+/- SD) time to ischemic
      electrical threshold was 53+/-60 s lower at -20 degrees C than at +20 degrees C
      (P=0.008), corresponding to a relative change of -8.0+/-10.5%. All other exercise
      parameters, including total exercise time and rate-pressure product, were
      unchanged during exposure to extreme cold. CONCLUSION: Exposure to extreme cold (
      20 degrees C) lowers the ischemic threshold during exercise testing in patients
      with CAD, even if asymptomatic or without a history of cold-induced angina.
      Patients with CAD and evidence of exertional angina or myocardial ischemia
      wishing to perform exercise at extremely low temperatures should discuss this
      matter with their physicians.

PMID- 20151060
TI  - The impact of treatment with omeprazole on the effectiveness of clopidogrel drug
      therapy during the first year after successful coronary stenting.
AB  - BACKGROUND: Because clopidogrel is converted to its active metabolite by P450
      isoenzymes, which are also involved in the metabolism of omeprazole, there is
      concern regarding whether the action of clopidogrel would be reduced in patients
      also taking omeprazole. OBJECTIVE: To evaluate the impact of omeprazole
      administration on the effectiveness of clopidogrel drug therapy during the first
      year following successful coronary stenting (CS). METHODS: A total of 588
      consecutive patients who underwent successful CS for stable or unstable coronary
      artery disease were studied. Patients were classified into those who were treated
      (group A, n=340) or not treated (group B, n=248) with omeprazole for seven or
      more consecutive days during the entire observation period. The composite of
      cardiac death or rehospitalization for nonfatal myocardial infarction during the
      first year was the prespecified primary study end point. RESULTS: Baseline
      characteristics, and dual clopidogrel and acetylsalicylic acid drug therapy were
      well balanced between the study groups. By one year, the primary end point was
      reached by 58 (9.9%) patients, including 20 (3.4%) who died due to cardiac
      reasons and 38 (6.5%) who were rehospitalized because of a nonfatal myocardial
      infarction. Patients in groups A and B, respectively, were at similar risk of the
      primary composite end point (10% versus 9.7%, hazard ratio 1.1 [95% CI 0.6 to
      1.8]; P=0.89). CONCLUSIONS: According to the results of the present study,
      treatment with omeprazole had no impact on the clinical efficacy of clopidogrel
      drug therapy during the first year after successful CS.

PMID- 20151062
TI  - An unusual presentation of atrial fibrillation.

PMID- 20151061
TI  - Benign cardiac tumours, malignant arrhythmias.
AB  - Four cases of pediatric cardiac tumours (PCTs) associated with ventricular
      arrhythmias are reported. Sudden cardiac death attributable to the tumour
      occurred in two children. A third child received an implantable cardioverter
      defibrillator and the fourth had persistent ventricular arrhythmia despite
      medical therapy. Most PCTs are considered benign; however, the development of
      malignant arrhythmias may complicate the management of these tumours in some
      patients. The literature regarding the arrhythmogenic potential of PCTs and the
      use of implantable cardioverter defibrillators in these patients is reviewed. The
      series highlights the deficiency of prognostic information for this cohort.

PMID- 20151063
TI  - Double interatrial septum.

PMID- 20151064
TI  - Electromagnetic interference induced by magnetic resonance imaging.

PMID- 20151065
TI  - Recurrent abdominal pain and weight loss in an adolescent: celiac artery
      compression syndrome.
AB  - Celiac artery compression syndrome is a rare cause of abdominal pain and weight
      loss, likely caused by compression of the celiac artery or plexus by the median
      arcuate ligament. A case of celiac artery compression syndrome in a 17-year-old
      male patient with severe postprandial pain and weight loss is described. Imaging
      techniques such as computed tomography, angiography and Doppler ultrasound
      identified the abnormality, which was corrected by laparoscopic surgery.

PMID- 20151067
TI  - Intermittent obstruction resulting from multiple intestinal webs.
AB  - Intestinal webs are a rare cause of bowel obstruction. A case of a 32-year-old
      man with multiple intestinal webs causing intermittent, partial bowel obstruction
      is described. The webs were initially detected with capsule endoscopy. The
      patient was treated with intraoperative endoscopy and balloon dilation. At early
      follow-up, no recurrence of his symptoms was evident.

PMID- 20151068
TI  - Positive celiac disease serology and reduced bone mineral density in adult women.
AB  - BACKGROUND: Low bone density and osteoporosis have been demonstrated in celiac
      disease populations in Europe, South America and the United States. Serological
      testing with tissue transglutaminase (TTG) and immunoglobulin A endomysial (EMA)
      antibodies is highly specific for celiac disease, while antigliadin antibody
      (AGA) testing is less specific. OBJECTIVE: To evaluate the association of celiac
      serology with reduced bone density in adult women. METHODS: A clinical database
      containing all bone density testing data in the province of Manitoba was linked
      to a database containing all celiac serology data for the province. The study
      cohort consisted of 376 women older than 20 years of age with bone density
      measurements preceding initial celiac serology by six months or less. Bone
      density was assessed in relation to TTG/EMA and AGA seropositivity, and compared
      with seronegative controls in age-, height- and weight-adjusted models. RESULTS:
      There was significantly lower bone density in TTG/EMA seropositive women than
      with seronegative controls for all sites tested (lumbar spine, total hip,
      trochanter, femoral neck; all P<0.05). TTG/ EMA seropositive women also had a
      significantly higher prevalence of osteoporosis (67.7% versus 44.8%; P<0.05).
      There was lower bone density at the three hip sites (all P<0.05) in AGA
      seropositive women, but after excluding TTG/EMA seropositive women, isolated AGA
      seropositivity showed no significant association with any bone density
      measurements. CONCLUSION: TTG/EMA seropositivity was associated with lower bone
      density and a higher prevalence of osteoporosis compared with seronegative
      controls.

PMID- 20151069
TI  - The changing frequency of celiac disease diagnosed at the Stollery Children's
      Hospital.
AB  - BACKGROUND: Celiac disease (CD) is recognized as one of the most common and
      important autoimmune gastrointestinal disorders affecting children. There is
      evidence that a diagnosis of CD during childhood improves health outcomes. The
      increasing prevalence of CD is due to increased awareness of the wide range of
      extraintestinal symptoms associated with CD. OBJECTIVE: To determine whether
      there has been a temporal increase in the diagnosis of CD associated with an
      increased diagnosis of children without typical gastrointestinal symptoms at the
      Stollery Children's Hospital (Edmonton, Alberta). METHODS: Patients with biopsy
      proven CD diagnosed at the Stollery Children's Hospital from 1998 to 2007, were
      identified by retrospective chart review. Baseline and follow-up data, including
      demographics, symptoms, risk factors, anthropometrics and laboratory
      investigations, were collected. RESULTS: An increase in the frequency of
      diagnosis of CD was noted during the study period, particularly from January 2003
      onward. Before January 2003, nine children were diagnosed with CD - all with
      typical symptoms. Between January 2003 and January 2007, inclusive, 149 children
      were diagnosed with CD, of whom 46% had absent or atypical symptoms. At follow
      up, 96% of patients reported improved symptoms, including 53% of individuals who
      reported being asymptomatic before diagnosis. CONCLUSIONS: In the last four years
      of the period studied, the number of children diagnosed with CD at Stollery
      Children's Hospital increased 11-fold. Screening children at risk for CD, and
      those with atypical presentations, contributed to the increased number of
      diagnoses. Identification of CD and establishment of lifelong, dietary gluten
      avoidance during childhood has important health benefits and should be
      encouraged.

PMID- 20151070
TI  - Gastroscopy following a positive fecal occult blood test and negative
      colonoscopy: systematic review and guideline.
AB  - BACKGROUND: A sizeable number of individuals who participate in population-based
      colorectal cancer (CRC) screening programs and have a positive fecal occult blood
      test (FOBT) do not have an identifiable lesion found at colonoscopy to account
      for their positive FOBT screen. OBJECTIVE: To evaluate the evidence and provide
      recommendations regarding the use of routine esophagogastroduodenoscopy (EGD) to
      detect upper gastrointestinal (UGI) cancers in patients participating in a
      population-based CRC screening program who are FOBT positive and colonoscopy
      negative. METHODS: A systematic review was used to develop the evidentiary base
      and to inform the evidence-based recommendations provided. RESULTS: Nine studies
      identified a group of patients who were FOBT positive and colonoscopy negative.
      Three studies found no cases of UGI cancer. Four studies reported cases of UGI
      cancer; three found UGI cancer in 1% or less of the population studied, and one
      study found one case of UGI cancer that represented 7% of their small subgroup of
      FOBT-positive/colonoscopy-negative patients. Two studies did not provide outcome
      information that could be specifically related to the FOBT-positive/colonoscopy
      negative subgroup. CONCLUSION: The current body of evidence is insufficient to
      recommend for or against routine EGD as a means of detecting gastric or
      esophageal cancers for patients who are FOBT positive/colonoscopy negative, in a
      population-based CRC screening program. The decision to perform EGD should be
      individualized and based on clinical judgement.

PMID- 20151071
TI  - Should my patient with inflammatory bowel disease on immunosuppressive therapy be
      vaccinated against influenza virus?
AB  - Crohn's disease and ulcerative colitis are variants of inflammatory bowel disease
      (IBD) for which immunosuppressive therapy is often required. Immunosuppressed
      patients are at increased risk for infections, including vaccine-preventable
      diseases such as influenza. Although several guidelines recommend routine
      influenza immunization for such patients, recent literature suggests that this
      patient population may be inadequately immunized. Current research suggests that
      inactivated influenza vaccines are effective, well tolerated and can be
      administered safely in most IBD patients. Studies in other immunosuppressed
      populations have also demonstrated the safety of inactivated vaccines. The
      present article reviews the literature regarding the safety and efficacy of
      influenza vaccination in IBD patients receiving immunosuppressive therapy.

PMID- 20151073
TI  - Anatomical and safety considerations in establishing portals used for canine
      elbow arthroscopy.
AB  - OBJECTIVES: To describe the relationship of the major muscular, ligamentous and
      neurovascular structures in relation to standard medial elbow arthroscopic
      portals used in dogs, and to evaluate their potential iatrogenic lesions. DESIGN:
      Anatomical study using 20 canine cadaveric elbows. METHODS: Arthroscopic
      explorations were performed using medial portals. Three 4 mm orthopaedic pins
      were introduced in place of the arthroscope, egress canula and instrumental
      portals. Limbs were dissected. Distances between pins and neurovascular
      structures were measured. Muscle, ligament and cartilage lesions were recorded.
      RESULTS: Minimal muscular lesions were observed. No ligament injury was
      evidenced. Superficial iatrogenic cartilage lesions were observed in three
      joints. The arthroscopic portal was 23.1 mm (range: 16 to 28.5 mm) caudal to the
      brachial artery, 21.0 mm (13-30.5 mm) caudal to the median nerve, and 4.0 mm (1-7
      mm) cranial to the ulnar nerve. The instrumental portal was 16.3 (9-24 mm) caudal
      to the brachial artery, 13.5 mm (7-24.5 mm) caudal to the median nerve, and 11.8
      (8-18 mm) cranial to the ulnar nerve. The egress portal was 21.4 mm (12-37 mm)
      caudal to the ulnar nerve. CONCLUSIONS AND CLINICAL RELEVANCE: The study
      confirmed the safety of elbow medial arthroscopic portals. Care must be taken
      when placing the camera portal so as to avoid injury of the ulnar nerve. Should
      extensive intra-articular procedures be needed, manipulation of instruments
      should be done cautiously in the cranio-medial compartment of the joint due to
      the proximity of the median nerve to the capsule.

PMID- 20151072
TI  - Mesalazine in inflammatory bowel disease: a trendy topic once again?
AB  - 5-aminosalicylic acid (5-ASA) preparations (eg, mesalazine, mesalamine) are well
      established preparations used in the management of inflammatory bowel disease.
      These drugs are most useful for the treatment of mild to moderate flares of
      ulcerative colitis and, especially, for maintenance of remission. Although most
      gastroenterologists are very familiar with these drugs, the interest in these
      drugs has undergone a resurgence, with new preparations offering convenience and
      high dosage, while preserving their customary safety. New dosage regimens are
      likely to become standard practice in the near future. There is also considerable
      interest in chemoprevention of colorectal cancer in the context of inflammatory
      bowel disease, and the role of long-term maintenance therapy with 5-ASAs in
      achieving such chemoprevention. A mechanism of action for such chemoprevention
      has been provided by the agonism of the peroxisome proliferator-activated
      receptor-gamma by 5-ASA, which unifies its efficacy as an anti-inflammatory and
      chemopreventive agent. In the future, even more effective agents based on 5-ASA
      are expected, based on more powerful agonism of peroxisome proliferator-activated
      receptor-gamma; 5-ASA preparations have become 'trendy' again.

PMID- 20151074
TI  - Headless self-compressing cannulated screw fixation for treatment of radial
      carpal bone fracture or fissure in dogs.
AB  - OBJECTIVES: To report the application and clinical outcome of the treatment of
      radial carpal bone fracture in five dogs using a variably-pitched, headless
      cannulated compression screw (Acutrak). METHODS: Arthroscopy was performed prior
      to surgical repair in three cases. In two cases, a fissure within the radial
      carpal bone was more clearly apparent when oblique indirect illumination was
      employed at arthrotomy. Following Acutrak screw placement via arthrotomy,
      external coaptation was applied in all cases for a period of two weeks. RESULTS:
      Five dogs were treated, of which four were Boxers, and one was a Labrador
      Retriever crossbreed. All dogs were lame prior to treatment. There was no history
      of trauma, and all dogs had soft tissue swelling on the dorsal aspect of the
      radiocarpal joint. In all cases the fissure or fracture line was oblique in
      orientation, extending disto-medially from the midpoint of the radiocarpal joint
      proximally to the level of the second carpal bone distally. All fractures treated
      demonstrated progressive radiographic healing, and all dogs were free of lameness
      at six weeks post- operatively, but two of the five fractures failed to reach
      complete radiographic union. All dogs remained lameness-free with mean follow-up
      of 12.5 months. DISCUSSION: Acutrak screws are headless devices which achieve
      compression, even in small bone fragments. Threads engage both the near and far
      fracture segments, leading to increased screw-bone contact which maximizes pull
      out strength and may increase the fatigue strength of the screw. CLINICAL
      SIGNIFICANCE: Fixation of two-piece canine radial carpal-bone fractures with the
      Acutrak screw proved a reliable alternative to conventional compression screw
      fixation, and may have benefits over alternatives attributable to screw design
      and application technique.

PMID- 20151075
TI  - The use of transarticular external skeletal fixation in the management of failed
      tibial tuberosity transposition in five dogs.
AB  - The management of tibial tuberosity fracture-avulsion after tibial tuberosity
      transposition can be challenging. Implants must be able to resist the strong
      distractive force of the quadriceps mechanism, yet implant size is limited by the
      amount of tuberosity bone stock available. Revision fixation is compromised
      further by fragmentation of the tubercle. Five stifle joints had temporary
      transarticular external skeletal fixators applied to manage complications of
      tibial tuberosity transposition. Fracture reduction was confirmed in four out of
      five tibial tuberosity fractures. Frames were in place for a mean of 44 days.
      Frame associated complications occurred in four out of five limbs, the most
      common being pin tract discharge and associated osteolucency. All frame
      associated complications resolved. Long-term follow-up information was available
      for three of the five animals at 13 to 18 months after frame removal. All three
      owners reported occasional lameness, but this was attributed to concurrent
      orthopaedic disease. Transarticular external skeleton fixation protects internal
      fixation techniques, and good limb function was achieved in most cases.
      Transarticular external skeleton fixation can be successfully used to augment
      repair of tibial tuberosity fracture after tibial tuberosity transposition.

PMID- 20151076
TI  - Modified Knowles toggle pin technique with nylon monofilament suture material for
      treatment of two caudoventral hip luxation cases.
AB  - The coxofemoral joint is the most commonly luxated joint in dogs and cats.
      Coxofemoral luxations are generally craniodorsal; caudoventral coxofemoral
      luxations are relatively rare occurrences and may be accompanied by fracture of
      the greater trochanter. The aim of our study was to report the results of a
      modified Knowles toggle pin application in two caudoventral hip luxations for
      which closed reduction had not been achieved. Medical records of dogs and cats,
      which had been presented at our institution between September 1999 and October
      2007, were reviewed for cases of coxofemoral luxation. In total, the case records
      of 67 cats and 147 dogs were found. Of these cases, there was one cat and one dog
      with caudoventral coxofemoral luxation. For both cases, the toggle pin technique
      was the method of treatment. The cat had a good clinical recovery within three
      days after surgery. The dog, which also had a cruciate ligament rupture in the
      same limb and medial patellar luxation in the contralateral limb, was presented
      with severe lameness and pain approximately two and a half months after surgery,
      at which time fracture of the femoral head was diagnosed. Functional recovery was
      achieved after a femoral head and neck ostectomy had been performed.

PMID- 20151077
TI  - Treatment of caudal mandibular fracture and temporomandibular joint fracture
      luxation using a bi-gnathic encircling and retaining device.
AB  - Fractures of the caudal portion of the mandible and temporomandibular joint (TMJ)
      fracture-luxation can be challenging to treat with direct fixation methods. This
      paper describes a simple technique for the indirect treatment of caudal
      mandibular fracture and TMJ fracture-luxation using a subcutaneous loop of nylon
      leader line tunnelled around the maxilla, incisive and nasal bones, and under the
      mandible, placed just caudal to the canine teeth, and crimped ventral to the
      mandibular skin: a bignathic encircling and retaining device (BEARD). A BEARD was
      used to treat two immature dogs with simple, unilateral caudal mandibular
      fractures, six cats with unilateral injury (two with TMJ luxation, three with TMJ
      fracture-luxation, one with caudal mandibular fracture), and two cats with
      bilateral injury (comminuted caudal mandibular fracture with contralateral TMJ
      luxation; bilateral condylar neck fracture). The BEARD treatment failed short
      term due to poor tolerance in one cat, and concurrent injuries and poor initial
      reduction in another cat. One cat was lost to long-term follow-up. Rostral dental
      occlusion was normal in six out of seven cases, and reported jaw function was
      normal in seven out of seven cases. The case with poor occlusion had imperfect
      initial reduction. Complications included dorsal nasal skin swelling or
      discharge, oesophagostomy tube dislodgement or blockage, BEARD loosening, and
      regurgitation. Treatment of uni- or bilateral caudal mandibular trauma using a
      BEARD can lead to clinical union, and normal rostral occlusion, provided that
      case selection is appropriate and immediate-post-surgical occlusion has been
      corrected.

PMID- 20151078
TI  - Bone transport osteogenesis for treatment of canine osteomyelitis. A report of
      two cases.
AB  - Bone transport osteogenesis, as described by Ilizarov, has been used to resolve
      segmental bone defects in both human and veterinary patients. These defects are
      created when a large osseous tumour, sequestrum, or non-union fracture is
      resected. This report documents two cases in which the principle of bone
      transport osteogenesis was applied by utilising the Ilizarov technique to bridge
      large osseous defects resulting from debridement of an infected nonunion fracture
      (case 1) and debridement of a sequestrum (case 2). Defects were treated by
      transporting either a complete or a hemi-circumferential bone segment. Both cases
      had resolution of osteomyelitis, satisfactory fracture union, and functional
      usage of the limb 39 weeks and 15 weeks post-surgery, respectively. Although
      manageable complications were encountered during the treatment of these cases,
      the long-term clinical outcome was eventually favorable. The authors believe that
      bone transport osteogenesis offers a valid restorative option in the treatment of
      bone defects resulting from extensive debridement and seque- strectomy.

PMID- 20151079
TI  - Macroscopic and microvascular blood supply of the canine common calcaneal tendon.
AB  - Chronic tendinopathy injuries to the canine common calcaneal tendon are
      relatively common in large breed dogs and typically affect the distal portion of
      the tendon. In humans, poor blood supply, biomechanical faults, poor training
      methods and fluoroquinolone administration have all been linked with the
      development of Achilles tendinopathy. The most common sites for Achilles
      tendinopathy in humans seem to correspond with areas of poor blood supply within
      the tendon. The aim of this study was to evaluate the blood supply of the canine
      common calcaneal (Achilles) tendon to determine if variations occur along the
      tendon. The null hypothesis was that there would be no difference in the
      microvascular blood supply at varying points along the tendon. Paired pelvic
      limbs were collected from 12 large breed dog cadavers. A 50% barium sulphate and
      50% saline solution was infused into the femoral artery of one limb from each dog
      and radiographs were taken to outline the blood supply to the common calcaneal
      tendon. Indian ink was infused into the contralateral limb. The common calcaneal
      tendon was removed, fixed and sectioned at 1 cm intervals, from calcaneal
      insertion to musculotendinous junction. The ink-filled arteries and arterioles in
      each section were counted. Radiographs revealed fine branches from the caudal
      saphenous artery entering the mid-body of the tendon along its cranial border.
      The musculotendinous junction had additional branches from the gastrocnemius
      muscles. Distally, vessels radiated proximally from the calcaneus 2 to 3 cm into
      the tendon. Mean total vessel counts at the insertion (138.54 +/- SD 31.06) were
      significantly higher than all other sections (p <0.001). The mid-body had
      significantly lower total vessel counts. When the cross sectional area of the
      tendon was taken into account, only the insertion had a significantly higher mean
      vessel count/cm2 than the mid-body of the tendon. There were no other significant
      differences in mean vessel count/cm2. Areas of poorer blood supply did not
      correspond with the most commonly reported site for chronic common calcanean
      tendinopathies, suggesting that inherent poor blood supply at the site of injury
      may not play a role in the pathogenesis. Atraumatic handling and minimal
      manipulation should be used during the surgical approach and debridement to
      preserve the remaining blood supply in ruptured tendons.

PMID- 20151080
TI  - A case of bilateral patellar osteochondrosis and fracture in a cat. Clinical and
      histological findings.
AB  - Fracture of the patella associated with bilateral osteochondrosis of the superior
      pole of the patella in a 14-week-old cat is reported with histological findings.
      Patellar osteochondrosis has been described in humans, horses, pigs, and dogs and
      is characterised by incomplete union of the ossification centres related to an
      abnormal process of endochondral ossification. However this disease has not yet
      been described in cats. Macroscopically, two main fragments separated by
      interposed tissue were identified on the left patella. In contrast, no fracture
      but only a fissuration of the articular cartilage was observed on the right
      patella. Bilateral partial patellectomy was performed. Histological examination
      of the excised fragments from the left patella revealed two main areas of
      trabecular bone separated by a wide irregular band of hyaline cartilage. The
      microscopic aspect of the right patella was similar to that of the left. Serial
      sections showed the initial appearance of an area of necrosis in the central band
      of hyaline cartilage, and that this hyaline cartilage was subsequently replaced
      by fibrovascular connective tissue. These findings indicate that some patellar
      fractures may be due to patellar osteochondrosis.

PMID- 20151081
TI  - Effect of exercise on kinetic gait analysis of dogs afflicted by osteoarthritis.
AB  - OBJECTIVE: To evaluate the effects of moderate exercise on kinetic gait analysis
      using a force platform in dogs with hindlimb lameness due to osteoarthritis (OA).
      METHODS: Ten control dogs (Control) and 10 dogs presented with chronic and stable
      hindlimb lameness (OA) were recruited. Dogs were subjected to force platform gait
      analysis to determine baseline data. They were thereafter trotted for a distance
      of 1.2 km on a short leash, lead by the same handler at a gait convenient for
      each of them (ranging from slow to fast trot), after which the gait analysis was
      immediately repeated to determine post-exercise values. Peak and impulse of the
      vertical and braking / propulsion forces were analysed using a linear model for
      repeated measures and Bonferroni sequential correction. RESULTS: In the Control
      group, the differences between baseline and post-exercise data were not
      significant. Conversely, post-exercise peak (p = 0.020) and impulse (p = 0.009)
      values of the vertical force, as well as the peak of the propulsion force (p =
      0.009) values were significantly lower than baseline in the OA group. CLINICAL
      RELEVANCE: This study demonstrates the significant effect of a moderate amount of
      exercise in exacerbating hindlimb lameness in dogs clinically afflicted by OA. It
      is suggested that: 1) exercise should be considered as a potential factor of
      variation in future force platform gait analyses and an effort should be made to
      limit bias in data recording; and 2) an exercise-based protocol could be added to
      the standard force platform gait analysis to potentially increase its sensitivity
      in the detection of lame dogs.

PMID- 20151082
TI  - Successful revision of a femoral head ostectomy (complicated by postoperative
      sciatic neurapraxia) to a total hip replacement in a cat.
AB  - A three-year-old neutered male Domestic Medium Hair cat was referred for
      evaluation of a right hindlimb monoparesis of one month duration following a
      femoral head ostectomy (FHO) performed elsewhere. Examination of the limb
      revealed muscle atrophy and decreased sensory perception over the sciatic nerve
      distribution with conscious proprioception and postural reaction deficits. The
      tentative diagnosis was sciatic neurapraxia. Radiographs taken prior to the FHO
      revealed a chronic nonunion right femoral neck fracture. The FHO was performed to
      remove the remnant of the femoral head and neck remaining in the acetabulum.
      Surgery was performed to explore the sciatic nerve and to revise the FHO into a
      total hip replacement. Sciatic nerve entrapment was present. Tethering sutures
      and extensive perineural adhesions were released to restore nerve gliding.
      Postoperatively, activity was limited for six weeks; normal activity resumed at
      eight weeks. Rehabilitation treatments were provided to maximise the patient's
      excellent recovery.

PMID- 20151083
TI  - Fracture of the anconeal process in two cats.
AB  - Two adult Domestic Shorthaired cats were presented with acute forelimb lameness.
      In one case, there was a history of trauma. A fracture of the anconeal process
      was diagnosed on the flexed mediolateral radiographs of the elbow in both cats.
      The fracture was accompanied by a bony avulsion of the tricipital tendon in one
      animal. Both cats underwent surgical removal of the fractured anconeal process.
      Follow-up radiographic evaluation was available for one cat six months after
      treatment; radiographs showed evidence of osteoarthritis. The long-term clinical
      outcome, based on owner telephone follow-up conducted four and nine years
      postoperatively, was considered to be satisfactory.

PMID- 20151084
TI  - Osteomyelitis-related sequestrum formation in association with the combination
      tibial plateau levelling osteotomy and cranial closing wedge osteotomy procedure.
AB  - A twenty-eight-month old female spayed American Bulldog was presented for
      evaluation of a chronic draining tract and intermittent left hindlimb lameness
      twenty-eight weeks after a combination tibial plateau levelling osteotomy and
      cranial closing wedge osteotomy (TLPO/CCWO) had been performed. The patient had
      developed an infection of the surgical site three weeks postoperatively. Drainage
      persisted despite implant removal 10 weeks postoperatively and several weeks of
      culture and sensitivity-directed antibiotic therapy. Twenty-eight weeks
      postoperatively, a sequestrum was identified on radiographs. Surgical removal of
      the sequestrum resulted in resolution of the drainage. While osteomyelitis is a
      known complication of TPLO surgery, this case represents the first described case
      of osteomyelitis-related sequestrum formation in association with the combined
      TPLO/CCWO procedure.

PMID- 20151085
TI  - Atopic dermatitis and ascariasis in children aged 2 to 10 years.
AB  - OBJECTIVE: To assess the association between atopic dermatitis (AD) and
      ascariasis in 2 to 10-aged children from the neighborhood Pedregal, in the city
      of Campina Grande, Brazil, an area of low socioeconomic index. METHODS: Cross
      sectional study conducted with the use of the standard questionnaire from the
      International Study of Asthma and Allergies in Childhood (ISAAC) and stool
      parasitological exam for Ascaris lumbricoides. The dependent variable was AD
      diagnosis: absent, mild, and severe. Multivariate logistic regression and
      descriptive analysis of the variable were used. Associations were estimated using
      relative risk (RR) and odds ratio (OR). The statistical inference was based on
      95% confidence intervals (95%CI). RESULTS: We assessed 1,195 children, 612
      (51.2%) female. The AD prevalence was 24.6%, and ascariasis prevalence was 26.1%.
      In the mild AD group of children, 44 (36.7%) were infected by A. lumbricoides
      while in the severe AD group, 40 (22.9%) had the same geohelminthosis (p = 0.01).
      Comparing negative cases of AD between mild and severe forms, the infection with
      A. lumbricoides increased the frequency of mild AD (RR = 1.7; p = 0.009), but not
      the severe form (RR = 0.86; p = 0.46). Evaluating only the positive cases of
      dermatitis, 120 mild AD (40.8%) and 176 with severe AD (58.2%), it can be said
      that the exposure to the parasite decreased the frequency of the severe form of
      dermatitis (RR = 1.46; p = 0.016). CONCLUSION: There is a high prevalence of AD
      and of ascariasis in the population studied. The severe AD is related to lower
      parasitemia of A. lumbricoides.

PMID- 20151086
TI  - Obesity and asthma: association or coincidence?
AB  - OBJECTIVE: Asthma and obesity are among the major causes of morbidity in
      childhood and adolescence. Early obesity increases the chances of chronic
      degenerative diseases in adults. Although the concomitance or both clinical
      situations are being demonstrated in various studies, the intrinsic mechanisms of
      this association are still very little known. Therefore, the objective of this
      article was to review the main studies on the association of obesity and asthma
      and check if there is a cause-effect relation between them. SOURCES: Systematic
      review based on indexed data bases MEDLINE (PubMed) and SciELO. Original articles
      (cross-sectional, case-control, and prospective studies) and meta-analysis
      published in the period that ranges from January 1998 to January 2008 were
      reviewed. Studies published in English, Spanish, and Portuguese were researched.
      SUMMARY OF THE FINDINGS: Although there are various studies on growing prevalence
      of asthma and obesity, few of them establish cause-effect relations between them.
      Physiopathological mechanisms and factors involved in this process are still
      little known. CONCLUSION: Methodological rigor in future studies must seek for
      answers to better understand if there is association between asthma and obesity
      or if the relationship between both diseases is a coincidence.

PMID- 20151088
TI  - Home-based palliative care: challenges in the care of technology-dependent
      children.
AB  - OBJECTIVES: To conceptualize palliative care and its indications in Pediatrics;
      to describe the difficulties involved in the delivery of such care at home for
      technology-dependent children; and to analyze, from a bioethical perspective, the
      moral dilemmas of palliative care assistance. SOURCES: A literature review of
      palliative care for technology-dependent children and a bioethical analysis of
      moral dilemmas. SUMMARY OF THE FINDINGS: There are several obstacles to
      palliative care for technology-dependent children: structural difficulties at
      home; social isolation of both children and families; health professionals' sense
      of disbelief regarding this type of care; an excessive number of medical devices
      at home; uncertainty of a terminal prognosis; physical, emotional, social,
      material, and financial burden for parents and family; changes in family dynamics
      to adjust to these children; paternalistic relationship between professionals and
      family; changes in family roles, with shifts in the caregiver role. CONCLUSIONS:
      It is essential to outline an agenda based on the premise that the medical
      apparatus for technology-dependent children will change the landscape of the
      home, and such a change might become a problem to be faced by all those living
      together. Based on this assumption, actions performed in a setting other than a
      health care facility might exert an actual protective effect on children and
      family, offering support in their several needs and developing a model of care
      delivery that includes interventions in the different levels of burden on these
      vulnerated and unprotected individuals.

PMID- 20151087
TI  - Influence of breastfeeding type and maternal anemia on hemoglobin concentration
      in 6-month-old infants.
AB  - OBJECTIVE: To verify the influence of breastfeeding type and of maternal anemia
      on hemoglobin concentration in 6-month-old infants. METHODS: This was a cross
      sectional study nested in a community-based, randomized and controlled
      intervention study that aimed to prolong the duration of exclusive breastfeeding
      during the first 6 months of life. This study was conducted in four towns in the
      Brazilian state of Pernambuco and newborn infants were recruited from March to
      August of 2001. The hemoglobin concentrations of 330 mothers and infants were
      assayed and type of breastfeeding was assessed 6 months after delivery.
      Multivariate linear regression analysis was used to identify factors that
      independently contributed to the infants' hemoglobin concentration. RESULTS: The
      type of feeding had no influence on the hemoglobin concentration in the sample as
      a whole, however, there was a significant difference when the "exclusive +
      predominant breastfeeding" subset of infants was analyzed, with the children of
      anemic mothers exhibiting a reduction of 0.7g/dL in median hemoglobin. Mothers'
      hemoglobin level, type of flooring at home, type of delivery, and birthweight all
      significantly contributed to the variation in the infants' hemoglobin
      concentration. CONCLUSIONS: In contrast with type of breastfeeding, maternal
      anemia did have an influence on the hemoglobin levels of 6-month-old infants,
      even when only children on "exclusive + predominant breastfeeding" were analyzed.
      These findings highlight the need to prevent maternal anemia before conception,
      during pregnancy and throughout lactation.

PMID- 20151089
TI  - Factors associated with intracranial hypertension in children and teenagers who
      suffered severe head injuries.
AB  - OBJECTIVE: To analyze factors associated with intracranial hypertension in
      pediatric patients who suffered severe head injuries. METHODS: Retrospective
      cohort study, with data collected from September 1998 through August 2003,
      including patients aged 0 to 16 who suffered severe head injuries, Glasgow score
      < 9, and submitted to intracranial pressure (ICP) monitoring (n = 132).
      Intracranial hypertension (IH) was defined as an episode of ICP > 20 mmHg
      requiring treatment, while refractory IH was ICP over 25 mmHg requiring
      barbiturates or decompressive craniectomy. Univariate analysis was followed by
      multivariate analysis; variables were considered significant if p < 0.05.
      RESULTS: Ages ranged from 2 months to 16 years, median age 9.7 (6.0-2.3) years.
      Glasgow scores ranged from 3 to 8, median 6 (4-7). Traffic accidents were
      responsible for 79.5% of events. Monitoring devices were installed, on average,
      14 hours after trauma, median time 24 hours. One hundred and three patients (78%)
      had IH, while 57 (43.2%) had refractory IH. In multivariate analysis, younger age
      ranges were associated with IH [relative risk = 1.67 (1.03-2.72); p = 0.037], and
      abnormal postures were associated with refractory IH [relative risk = 2.25 (1.06
      4.78)]. The group mortality rate was 51.5%; it was correlated with use of
      barbiturates in refractory IH and low cerebral perfusion pressure at the
      intensive care unit. CONCLUSIONS: IH and refractory IH were frequent events in
      pediatric patients who suffered severe head injuries. The younger the patient,
      the greater the chance of developing IH. The presence of abnormal postures was
      found to be a risk factor for refractory IH.

PMID- 20151090
TI  - Frequency of public child care service use and associated factors.
AB  - OBJECTIVE: Assess the maternal socio-demographic factors associated with the
      frequency of use of child care services by low income families. METHODS: Cross
      sectional analysis of 393 children between 12 and 16 months old who participated
      in a randomized field trial during their first year of life in a program of
      nutritional intervention. The study began in the Brazilian Unified Health System
      (Sistema Unico de Saude, SUS) of the maternity hospital in the city of Sao
      Leopoldo, state of Rio Grande do Sul, Brazil. Children were examined regarding
      child care follow-up and vaccination schedule by checking the immunization chart.
      Data were analyzed using statistical tests Pearson's chi square and prevalence
      ratio (PR) with respective 95% confidence interval. RESULTS: The frequency of
      children who were not continuously taken to the child care service was 53.2%.
      Multivariate analysis suggests that the factors associated with the lack of
      continuous use of the service were: mother's educational level <or= 8 years (PR
      1.32 95%CI 1.02-1.71), non-nuclear family structure (PR 1.32 95%CI 1.10-1.59) and
      not being an only child (PR 1.38 95%CI 1.10-1.72). The reasons for lack of follow
      up, according to the mothers were: the fact that they thought it unnecessary for
      66.2%, problems with the service for 21.7%, difficulties related to their jobs
      for 6.05%, and other reasons for 6.05%. CONCLUSION: The high frequency of
      children who were not taken to the child health care service for follow-up is
      associated with low maternal educational level and family structure, as well as
      the perception that follow-up visits are not necessary when the child does not
      have a disease.

PMID- 20151091
TI  - Estimation of energy and macronutrient intake at home and in the kindergarten
      programs in preschool children.
AB  - OBJECTIVE: To estimate the energy and macronutrient intake at home and at all-day
      in the kindergarten programs in children aged 2 to 6 and to investigate
      differences in consumption and intake between children at public and private
      kindergartens. METHODS: This was a cross-sectional study of 362 preschool
      children from Caxias do Sul, Brazil. Nutritional status was assessed in terms of
      weight to height ratios. Foods consumed in the kindergarten were evaluated by
      weighing the actual foods eaten by the children and home intakes were calculated
      from a food diary kept by parents or guardians. Statistical analyses were
      performed using the Mann-Whitney U test (p < 0.05). RESULTS: It was found that 28
      children (7.7%) were overweight, 92 (25.4%) were at risk of becoming overweight
      and seven (1.9%) were classified as having wasting. Analysis of 24-hour
      nutritional intake demonstrated that 51.3% of the energy, 60.3% of the lipids and
      51.6% of the proteins consumed by children were eaten at home, despite the
      children spending the whole day in the kindergarten programs. Preschool children
      at kindergartens ate greater quantities of energy (p = 0.001), carbohydrates (p <
      0.001), and lipids (p = 0.04) than did children at public kindergartens, but
      their total daily intakes were similar, irrespective of which type of
      kindergarten program children attended. CONCLUSIONS: The findings suggest that
      these children eat proportionally more energy, proteins and lipids in their extra
      meals at home than they do in their daytime meals in the kindergarten programs.
      Despite the differences in intake between public and private kindergarten, daily
      intakes were similar.

PMID- 20151092
TI  - Evaluation of implementation of humanized care to low weight newborns - the
      Kangaroo Method.
AB  - OBJECTIVE: To evaluate the implementation of the kangaroo mother method in
      hospitals trained by the Brazilian Ministry of Health. METHOD: Cross-sectional
      study, evaluating 176 (60.1%) out of 293 hospitals that were trained by the
      Brazilian Ministry of Health from 2000 to 2003 in Brazil. This study was
      conducted in two phases. The first phase consisted of sending a questionnaire to
      293 hospitals; in the second phase an in loco visit was made in a sample of 29
      among those hospitals. The instrument for data collection was sent to all
      hospitals by mail, fax or e-mail through the Ministry of Health and they
      addressed the three dimensions of the normative assessment: structure, processes,
      and results. The second phase consisted of an evaluation of the process, using a
      structured guide of non-participant observation. To estimate the reliability of
      the variable "deployment of the steps of the method" between questionnaire and
      site visit, we used the kappa test. RESULTS: The first stage of the kangaroo
      mother method was implemented in 84.9% of the hospitals, but only 47.3% of them
      implemented the three stages according to the Brazilian norm. The kappa test
      results indicated a moderate agreement for the first stage, and substantial for
      the second and third stages of the method. CONCLUSION: Hospital training was
      important for triggering the implementation process of the kangaroo mother
      method. However, they were not enough to promote the implementation of the three
      phases of the method.

PMID- 20151093
TI  - Lipodystrophy syndrome and cardiovascular risk factors in children and
      adolescents infected with HIV/AIDS receiving highly active antiretroviral
      therapy.
AB  - OBJECTIVE: To describe lipid profile, body shape changes, and cardiovascular risk
      factors in children and adolescents infected with HIV/AIDS receiving highly
      active antiretroviral therapy. METHODS: We investigated 43 children and
      adolescents being treated with this therapy at the outpatient clinic of pediatric
      infectious diseases of Instituto Fernandes Figueira/Fundacao Oswaldo Cruz, Rio de
      Janeiro, Brazil. Values of total cholesterol, high-density lipoprotein, low
      density lipoprotein, and triglycerides were determined. We also performed glucose
      tolerance test and analyzed body fat distribution, nutritional status, dietary
      intake, and family history of cardiovascular risk. The statistical analysis was
      performed using Student's t test. Significance level of p-value was lower than
      0.05. RESULTS: We found lipid abnormality in 88.3% and body shape change in 13.9%
      of the cases. Nutritional status was adequate (81.3%) in most of the study
      population. Cholesterol intake in children older than 9 years was above the
      recommended value. CONCLUSION: Prevalence of dyslipidemia and, therefore, risk
      for cardiovascular diseases were high during the use of highly active
      antiretroviral therapy.

PMID- 20151094
TI  - Neonatal near miss approach in the 2005 WHO Global Survey Brazil.
AB  - OBJECTIVES: To explore the use of the neonatal near miss concept as a tool to
      evaluate the quality of neonatal care, as 3 million early neonatal deaths occur
      every year around the world and the majority of these deaths are avoidable and
      take place in developing countries. METHODS: This is a secondary analysis of the
      2005 WHO Global Survey on Maternal and Perinatal Health, a cross-sectional study,
      using data from 19 randomly selected Brazilian hospitals. A pragmatic definition
      of neonatal near miss was developed and tested. Near miss indicators were
      calculated. RESULTS: Among the 15,169 live born infants included in this
      analysis, 424 presented at least one of the following conditions: very low birth
      weight, less than 30 gestational weeks at birth or an Apgar score at the 5th
      minute of life less than 7. According to the operational definition, these
      survivors from life-threatening conditions were considered neonatal near miss
      cases. The early neonatal mortality rate was 8.2/1,000 live births, the neonatal
      near miss rate was 21.4 neonatal near miss cases/1,000 live births. Substantial
      variations in the mortality among neonates with life-threatening conditions at
      birth were observed suggesting intra-hospital quality of care issues. CONCLUSION:
      The near miss concept and indicators provided information that could be useful to
      evaluate the quality of care and set priorities for further assessments and
      health care improvement for newborn infants.

PMID- 20151095
TI  - Hepatic steatosis in a school population of overweight and obese adolescents.
AB  - OBJECTIVE: To assess hepatic steatosis by ultrasound method as a concomitant risk
      factor among overweight adolescents. METHODS: A case-control study including 83
      cases (47 overweight and 36 obese) and 89 controls (normal weight), frequency
      matched by gender, year of birth, pubertal stage (Tanner 4/5), and income. Cases
      and controls were selected from 1,420 students enrolled in a Vila Mariana public
      high school, in Sao Paulo, Brazil. Must et al. criteria were used for nutritional
      status classification. Nonalcoholic fatty liver disease was diagnosed through
      hepatic ultrasonography performed and analyzed by one radiologist. Hepatic
      enzymatic activities (alanine and aspartate transaminases, alkaline phosphatase,
      gamma-glutamyl transpeptidase) and direct bilirubin were measured. Eight
      covariables were fitted into logistic regression models; criterion for inclusion
      of variables was the association with overweight in the bivariate analyses (p <
      0.20). A value of p < 0.05 was set as the criterion for inclusion into the final
      logistic regression models. RESULTS: Prevalence of hepatic steatosis diagnosed
      through ultrasonography was 27.7% in overweight/obese students and 3.4% in normal
      weight students. Adjusted odds ratios (95%CI) for images compatible with
      nonalcoholic fatty liver disease and gamma-glutamyl transpeptidase > 24 U/L were
      10.77 (2.45-47.22) and 4.18 (1.46-11.94), respectively. CONCLUSIONS: This is the
      first population-based study showing that hepatic steatosis is strongly
      associated with overweight/obesity among adolescents attending a Brazilian public
      school. The diagnostic tool used in this investigation is a non-invasive method
      that might be applied to monitor overweight and obese adolescents and to propose
      actions for preventing more severe hepatic diseases in adulthood.

PMID- 20151096
TI  - Differential diagnosis of neonatal cholestasis: clinical and laboratory
      parameters.
AB  - OBJECTIVE: To evaluate if clinical and laboratory parameters could assist in the
      differential diagnosis of intra and extra-hepatic neonatal cholestasis (NC).
      METHODS: Retrospective study of NC patients admitted at the Pediatric Hepatology
      Outpatient Clinic of the teaching hospital of Universidade Estadual de Campinas
      (UNICAMP), Campinas, Brazil, between December 1980 and March 2005. The approach
      to the diagnosis of NC was standardized. According to diagnosis, patients were
      classified into two groups: I (intra-hepatic neonatal cholestasis) and II (extra
      hepatic neonatal cholestasis). In order to verify if there was association with
      the categorical variable, the chi-square and Mann-Whitney tests were used, with
      corrections for age for the covariance analysis (ANCOVA). The determination of
      accuracy of the clinical and laboratory variables for differentiation of the
      groups was made using the analysis of the ROC curve. RESULTS: One hundred and
      sixty-eight patients were evaluated (group I = 54.8% and group II = 45.2%). In
      the patients with less than 60 days of life there was predominance of intra
      hepatic causes, whereas, in those older than 60 days, there was predominance of
      extra-hepatic etiology (p < 0.001). Median birth weight was lower in group I (p =
      0.003), as well as length at birth (p = 0.007). Median values of direct bilirubin
      were higher in group II (p = 0.006). Values of gamma-glutamyltransferase (GGT)
      (10 times higher than the limit of normality) presented sensitivity of 56.3%,
      specificity of 91.5%, and accuracy of 75.7% for the diagnosis of extra-hepatic
      cholestasis. CONCLUSION: In the present study, extra-hepatic NC presented greater
      weight and length at birth, fecal hypocholia/acholia, choluria, hepatomegaly,
      increase in GGT (10.8 times higher than the limit of normality), and a delay for
      investigation in the tertiary center.

PMID- 20151097
TI  - Neonatal near miss: a potentially useful approach to assess quality of newborn
      care.

PMID- 20151098
TI  - The next decade: cardiovascular risks, outcomes, prevention, and treatment in
      pediatric HIV infection.

PMID- 20151099
TI  - Airline acceptability of CPAP: is relevant information available on airlines'
      websites?

PMID- 20151100
TI  - [Medical and medical ethical basis of precautionary options].
AB  - The main activities of anesthesiologists in addition to the operation theatre are
      intensive and emergency treatment as well as pain and palliative care.
      Discussions and decisions about strategies and enforcement of therapy are
      indispensable in all areas. Acknowledgment of the patients' wishes and protection
      of patient autonomy are very important in the context of medical fiduciary duty.
      Determination of the aim of therapy and the patient's prognosis are of special
      importance. Against the background of the current amendments of patient advance
      directives different possibilities, such as advance directive and emergency forms
      in different areas of anesthesiology will be discussed.

PMID- 20151101
TI  - [New regulation of patient advance directives : What are the consequences for the
      practice?].
AB  - The inclusion of patient advance directives in the German Civil Code by the legal
      institution represents on the one hand a partial regulation of the total
      complex"euthanasia". On the other hand this goes far beyond the target as this is
      not only valid for cases involving fatal diseases. The legislation has, however,
      still not clarified all questions in connection with euthanasia and advance
      directives. Many legal uncertainties remain and even the partial regulation
      itself contains substantial ambiguities and gaps. In the following article
      clearly answerable basic questions on euthanasia will be presented and the
      disputed problems and the content of the amendment will be discussed.

PMID- 20151102
TI  - [Perioperative management of patients with coronary stents in non-cardiac
      surgery].

PMID- 20151103
TI  - [Chest compression quality : Can feedback technology help?].
AB  - BACKGROUND: The outcome of cardiopulmonary resuscitation (CPR) depends on the
      quality of chest compressions. Current European Resuscitation Council (ERC)
      guidelines promote the development of feedback systems. However, no studies
      presenting satisfactory results of feedback use have been published. METHODS: A
      total of 60 patients with cardiac arrest (> or =18 years of age) received
      resuscitation attempts using an automated external defibrillator (AED) with real
      time feedback by the ambulance service of the City of Munster. The frequency of
      chest compressions, no-flow time (NFT) and depth of chest compressions were
      analyzed for the first three cycles of CPR and compared to the ERC guidelines
      2005. RESULTS: Chest compression frequency did not differ significantly from the
      ideal as set out in the guidelines. Analysis of NFTs showed significantly longer
      NFT for the first cycle but NFT for the second and third cycles did not differ
      significantly from the ideal. The target depth of 4-5 cm was achieved in 80% of
      all chest compressions in the first 3 cycles. CONCLUSION: With the AED real-time
      feedback technology used in this study standardized performance of chest
      compressions could be maintained in a professional ambulance service.
      Implementation of a feedback system requires training of ambulance staff.

PMID- 20151104
TI  - Identification of differentially expressed small non-protein-coding RNAs in
      Staphylococcus aureus displaying both the normal and the small-colony variant
      phenotype.
AB  - The emerging interest in RNA research is due to the discovery that bacterial non
      protein-coding RNAs (npcRNAs; often referred to as "non-coding RNAs") are central
      regulatory molecules. While single npcRNAs have been described in Staphylococcus
      aureus, mostly based on computational-based approaches, experimental data on
      npcRNAs and their impact on the formation of different phenotypes of S. aureus
      are missing. Consequently, two specialized cDNA libraries were constructed from
      total RNA collected from different growth phases of an isogenic clinical strain
      pair of S. aureus displaying both the normal and the small-colony variant
      phenotype. Overall, 142 candidates for novel npcRNAs were identified and their
      expression analyzed by Northern blot assays. Of these, the presence of 18 novel
      npcRNAs in S. aureus was experimentally confirmed. In fact, growth phase-specific
      regulation was detected for almost all of the novel npcRNAs, with different
      npcRNA expression patterns detectable for both phenotypes. Of particular
      interest, S. aureus phenotype-specific expression of four novel npcRNAs was
      documented. Thus, the presence of differentially expressed npcRNAs in S. aureus
      may help to understand the phenotypic variation and its associated pathogenicity.

PMID- 20151105
TI  - Potential gene flow of two herbicide-tolerant transgenes from oilseed rape to
      wild B. juncea var. gracilis.
AB  - Four successive reciprocal backcrosses between F(1) (obtained from wild Brassica
      juncea as maternal plants and transgenic glyphosate- or glufosinate-tolerant
      oilseed rape, B. napus, as paternal plants) or subsequent herbicide-tolerant
      backcross progenies and wild B. juncea were achieved by hand pollination to
      assess potential transgene flow. The third and forth reciprocal backcrosses
      produced a number of seeds per silique similar to that of self-pollinated wild B.
      juncea, except in plants with glufosinate-tolerant backcross progeny used as
      maternal plants and wild B. juncea as paternal plants, which produced fewer seeds
      per silique than did self-pollinated wild B. juncea. Germination percentages of
      reciprocal backcross progenies were high and equivalent to those of wild B.
      juncea. The herbicide-tolerant first reciprocal backcross progenies produced
      fewer siliques per plant than did wild B. juncea, but the herbicide-tolerant
      second or third reciprocal backcross progenies did not differ from the wild B.
      juncea in siliques per plant. The herbicide-tolerant second and third reciprocal
      backcross progenies produced an amount of seeds per silique similar to that of
      wild B. juncea except for with the glufosinate-tolerant first and second
      backcross progeny used as maternal plants and wild B. juncea as paternal plants.
      In the presence of herbicide selection pressure, inheritance of the glyphosate
      tolerant transgene was stable across the second and third backcross generation,
      whereas the glufosinate-tolerant transgene was maintained, despite a lack of
      stabilized introgression. The occurrence of fertile, transgenic weed-like plants
      after only three crosses (F(1), first backcross, second backcross) suggests a
      potential rapid spread of transgenes from oilseed rape into its wild relative
      wild B. juncea. Transgene flow from glyphosate-tolerant oilseed rape might be
      easier than that from glufosinate-tolerant oilseed rape to wild B. juncea. The
      original insertion site of the transgene could affect introgression.

PMID- 20151107
TI  - Arthroscopic anterior cruciate ligament reconstruction with modified "wireless"
      cross-screw transfix femoral fixation.
AB  - Among several graft fixation options in arthroscopic ACL reconstruction for
      hamstring tendons, transcondylar fixation has been suggested to offer mechanical
      advantages compared to other femoral fixation systems. Blind nature of the
      procedure may result in several complications including iliotibial band
      irritation syndrome, breakage of the bio absorbable cross-pin, stress fracture of
      the femoral cortex, and more commonly intraoperative wire loop twisting,
      resulting in fixation failure, wire breakage or graft laceration. We used
      "wireless" transfixation technique to avoid complications associated with wire
      loop.

PMID- 20151106
TI  - Soluble ST2 plasma concentrations predict mortality in severe sepsis.
AB  - PURPOSE: Patients with sepsis-after surviving the initial hyperinflammatory phase
      display features consistent with immunosuppression, including hyporesponsiveness
      of immunocompetent cells to bacterial agents. Immunosuppression is thought to be
      facilitated by negative regulators of toll-like receptors, including membrane
      bound ST2. We investigated the release of soluble ST2 (sST2), a decoy receptor
      that inhibits membrane-bound ST2 signaling, during sepsis. METHODS: The study
      population comprised 95 patients with severe sepsis admitted to one of two
      intensive care units (ICUs) at the day the diagnosis of severe sepsis was made.
      Blood was obtained daily from admission (day 0) until day 7 and finally at day
      14. Twenty-four healthy subjects served as controls. sST2 and cytokines were
      measured in serum. RESULTS: Mortality among patients was 34% in the ICU and 45%
      in the hospital. On admission, sepsis patients had higher sST2 levels [10,989
      (7,871-15,342) pg/ml, geometric mean (95% confidence interval, CI)] than controls
      [55 (20-145) pg/ml, P < 0.0001]. Serum sST2 remained elevated in patients from
      day 0 to 14 and correlated with disease severity scores (P < 0.001) and cytokine
      levels on day 0 and during course of disease (P < 0.0001). Nonsurvivors displayed
      elevated sST2 levels compared with survivors of the intensive care unit (P <
      0.0001). CONCLUSIONS: Sepsis results in sustained elevation of serum sST2 levels,
      which correlates with disease severity and mortality.

PMID- 20151108
TI  - Lateral sided snapping elbow caused by a meniscus: two case reports and
      literature review.
AB  - Lateral sided snapping elbow is an unusual condition, and it is apt to be
      misdiagnosed as lateral epicondylitis. The causes of lateral sided snapping elbow
      have been attributed to intraarticular loose bodies, instability, synovial plicae
      and torn annular ligament. We report our experiences for treating lateral sided
      snapping elbow caused by a meniscus in the radio-humeral joint. In the present
      cases, the cause of snapping was detected using double contrast arthrogram under
      fluoroscopic control, and histology revealed that it was a meniscus. Complete
      removal of the meniscus allowed immediate relief of the symptom, and there was no
      recurrence in both cases.

PMID- 20151109
TI  - Arthroscopic treatment of chronic calcific tendinitis with complete removal and
      rotator cuff tendon repair.
AB  - Relatively large calcific materials on radiographs of shoulders with persistent
      symptoms after extended periods of conservative treatment are candidates for
      operative treatment. But complete removal of calcific materials sometimes leaves
      a large defect in the rotator cuff tendon, and tendon repair might be essential
      if defects are large. We evaluated the clinical results of complete removal of
      calcific deposits with or without repair of the rotator cuff tendon in 35
      consecutive patients. Eighteen patients underwent calcific material removal,
      which resulted in a complete tear in the rotator cuff tendon, and suture anchor
      repair. And the other 17 patients received either side-to-side repair or simple
      debridement. Clinical outcomes improved at a median 31 (range 24-45) months after
      surgery, and pain relief was achieved within 6 months of surgery in 30 of 35.
      However, ten patients developed a secondary stiff shoulder. Repair with or
      without suture anchor after complete removal of calcific material provides good
      clinical results and earlier pain relief when it was compared to previous
      literatures of minimal removal technique.

PMID- 20151110
TI  - Osteochondral defects in the ankle: why painful?
AB  - Osteochondral defects of the ankle can either heal and remain asymptomatic or
      progress to deep ankle pain on weight bearing and formation of subchondral bone
      cysts. The development of a symptomatic OD depends on various factors, including
      the damage and insufficient repair of the subchondral bone plate. The ankle joint
      has a high congruency. During loading, compressed cartilage forces its water into
      the microfractured subchondral bone, leading to a localized high increased flow
      and pressure of fluid in the subchondral bone. This will result in local
      osteolysis and can explain the slow development of a subchondral cyst. The pain
      does not arise from the cartilage lesion, but is most probably caused by
      repetitive high fluid pressure during walking, which results in stimulation of
      the highly innervated subchondral bone underneath the cartilage defect.
      Understanding the natural history of osteochondral defects could lead to the
      development of strategies for preventing progressive joint damage.

PMID- 20151111
TI  - Disease-specific clinical problems associated with the subchondral bone.
AB  - The subchondral bone is involved in a variety of diseases affecting both the
      articular cartilage and bone. Osteochondral defects in distinct locations and of
      variable sizes are the final results of different etiologies. These include
      traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and
      osteoarthritis. Traumatic osteochondral defects are caused by osteochondral
      fractures, separating an osteochondral fragment that includes articular cartilage
      and both subchondral and trabecular bone from the joint surface. In
      osteochondritis dissecans, the disease originates in the subchondral bone and
      secondarily affects the articular cartilage. Location, stage, size, and depth of
      osteochondral lesions play a role in the treatment of traumatic osteochondral
      defects and osteochondritis dissecans. Surgical options include fragment
      refixation, transplantation of osteochondral autografts, or bone restoration by
      impacted cancellous bone grafts combined with autologous chondrocyte
      transplantation. An insufficiency fracture of the subchondral bone may be the
      initiating factor of what was formerly believed to be a spontaneous osteonecrosis
      of the knee (SPONK). Recent histopathological studies suggest that each stage of
      SPONK reflects different types of bone repair reactions following a fracture of
      the subchondral bone plate. Osteoarthritis is a disease that does affect not only
      the articular cartilage, but also the subchondral bone. Reconstructive surgical
      techniques aim at preserving joint function, inducing fibrocartilaginous repair,
      and at correcting malalignment. This review summarizes the current status of the
      clinical treatment of traumatic osteochondral defects, osteochondritis dissecans,
      osteonecrosis, and osteoarthritis as they affect the subchondral bone region and
      its adjacent structures.

PMID- 20151112
TI  - Autologous transplantation of adult adipose derived stem cells into rabbit
      urethral wall.
AB  - INTRODUCTION AND HYPOTHESIS: A study was carried out to evaluate the feasibility
      of autologous adipose derived stem cells (ADSC) transplantation into female
      rabbits' urethra walls as an alternative to intrinsic urethral regeneration.
      METHODS: Inguinal fat pad of 12 New Zealand adult female rabbits were harvested
      and processed to obtain stromal vascular fraction (SVF). The SVF were platted to
      isolate ADSC. Before urethral injection, cells were labeled with DiI marker. The
      urethra wall was injected with 1 x 10(7) autologous cells or saline (sham). The
      urethra was harvested at 2, 4, and 8 weeks to identify DiI-labeled cells.
      RESULTS: At 2 and 4 weeks, the ADSCs create a nodule localized in the urethral
      sub-mucosa. At 8 weeks, the ADSCs spread and integrated with the urethra wall
      from the initial injection site. CONCLUSION: This is the first study to
      demonstrate a successful autologous ADSCs transplantation. It confirms that ADSCs
      can survive and integrate within the urethral wall.

PMID- 20151113
TI  - Encystation process of Giardia lamblia: morphological and regulatory aspects.
AB  - One important step in the life cycle of the pathogenic protozoan Giardia lamblia
      is the transformation of the proliferative form, the trophozoite, into the non
      proliferative cyst. This process, known as encystation, can be triggered in
      vitro. Morphological analysis showed that during trophozoite-cyst transformation,
      major changes take place: modification of the protozoan shape, internalization of
      the flagella, fragmentation of the adhesive disk, and appearance of encystation
      vesicles (ESVs), which later on fuse with the plasma membrane forming the cell
      wall. Sites of attachment of these vesicles to the inner portion of the protozoan
      plasma membrane were observed 6 h after the beginning of the encystation process.
      These sites were only visible when we used high-resolution scanning electron
      microscopy to study Giardia surface. In order to analyze the involvement of
      protein kinases and phosphatases on the encystation process, inhibitors of these
      enzymes were added to the culture medium, and their effect on the differentiation
      process was determined using light, immunofluorescence, and electron microscopy.
      Significant inhibition was observed with LY294002, an inhibitor of PI3 kinase;
      genistein, an inhibitor of tyrosine kinase; and staurosporine, at concentrations,
      which inhibit protein kinase C. Okadaic acid, an inhibitor or protein
      phosphatase, and wortmannin, an inhibitor of PI3K, did not interfere with the
      encystation process. However, they induced the appearance of large and
      pleomorphic forms where several nuclei and disorganization of the peripheral
      vesicles were observed.

PMID- 20151114
TI  - Correlation between lactosylation and denaturation of major whey proteins: an
      investigation by liquid chromatography-electrospray ionization mass spectrometry.
AB  - The Maillard-reaction-induced lactosylation of the major whey proteins, alpha
      lactalbumin (alpha-La) and beta-lactoglobulins (beta-Lg) A and B, occurring upon
      heating at 70, 80 and 90 degrees C for 1 to 5 h in the presence of lactose
      excess, was studied by HPLC coupled to electrospray ionization single and tandem
      mass spectrometry (HPLC-ESI-MS, MS/MS). The presence of significant amounts of
      mono and bi-lactosylated forms of the three proteins and their increase with
      heating temperature and time were assessed from MS data. Evidences for a
      concomitant, significant denaturation, involving partial tertiary structure
      unfolding, were also obtained in the case of beta-lactoglobulins. A subsequent
      ESI-MS and MS/MS investigation on the tryptic digests of heated protein solutions
      exhibiting high percentages of mono and bi-lactosylated forms provided
      information on lactosylation sites. In particular, the latter were identified
      both on tryptic and on aspecific peptides, whose unusual relevance (compared to
      similar studies) was found to be due mainly to heat-induced protein degradation,
      occurring before protein digestion with trypsin. Among lactosylation sites
      identified only on tryptic peptides, i.e., those reasonably related to intact
      protein lactosylation, two lysines residues were found for alpha-La, both located
      in accessible regions of its tertiary structure. In the case of beta-Lg, besides
      three sites common to variants A and B (leucine 1, lysines 70, and 75), lysine 69
      was found to be lactosylated only in variant B. Its proximity to a critical
      region of beta-Lg tertiary structure suggests that the difference between the two
      variants could be ascribed to a different evolution of their conformation upon
      heating.

PMID- 20151115
TI  - Stochasticity versus determinism: consequences for realistic gene regulatory
      network modelling and evolution.
AB  - Gene regulation is one important mechanism in producing observed phenotypes and
      heterogeneity. Consequently, the study of gene regulatory network (GRN)
      architecture, function and evolution now forms a major part of modern biology.
      However, it is impossible to experimentally observe the evolution of GRNs on the
      timescales on which living species evolve. In silico evolution provides an
      approach to studying the long-term evolution of GRNs, but many models have either
      considered network architecture from non-adaptive evolution, or evolution to non
      biological objectives. Here, we address a number of important modelling and
      biological questions about the evolution of GRNs to the realistic goal of biomass
      production. Can different commonly used simulation paradigms, in particular
      deterministic and stochastic Boolean networks, with and without basal gene
      expression, be used to compare adaptive with non-adaptive evolution of GRNs? Are
      these paradigms together with this goal sufficient to generate a range of
      solutions? Will the interaction between a biological goal and evolutionary
      dynamics produce trade-offs between growth and mutational robustness? We show
      that stochastic basal gene expression forces shrinkage of genomes due to
      energetic constraints and is a prerequisite for some solutions. In systems that
      are able to evolve rates of basal expression, two optima, one with and one
      without basal expression, are observed. Simulation paradigms without basal
      expression generate bloated networks with non-functional elements. Further, a
      range of functional solutions was observed under identical conditions only in
      stochastic networks. Moreover, there are trade-offs between efficiency and yield,
      indicating an inherent intertwining of fitness and evolutionary dynamics.

PMID- 20151116
TI  - Antiapoptotic effect of angiotensin-II type-1 receptor blockade in renal tubular
      cells of hyperoxaluric rats.
AB  - In this study, we investigated the protective effect of losartan as an AT1
      receptor antagonist by evaluating the expression of apoptosis-regulatory genes
      that contribute to the progressive damage in the renal tubules of hyperoxaluric
      rats. Rats were divided into 4 groups of 10 each; control (C), ethylene glycol
      (EG), ethylene glycol + losartan (EG + L) and Losartan (L). For 4 weeks 0.8% EG,
      as a precursor for oxalate, was administered to EG and EG + L and losartan (300
      mg/l) was administered to groups EG + L and L. Urine and blood samples were
      collected for biochemical determination. Bcl-2, bax, caspase-3 and TGF-beta 1
      antibodies were used for immunohistochemistry. Apoptosis was determined by TUNEL
      method. A marked increase in urinary oxalate levels of the rats in EG and EG + L
      groups was found. In the EG group a diffuse amount of oxalate crystals into the
      tubular lumina and interstitium in the cortex was observed. In the EG group GBM
      thickening, interstitial fibrosis and tubular atrophy with infiltration of
      mononuclear cell findings reduced in the EG + L group were presented as well. In
      the EG group, immunoreactivity of TGF-beta 1 was increased in glomeruli and
      tubuli. In the EG + L group, immunoreactivity of TGF-beta 1 was decreased
      compared to the EG group. Bax expression increased in the renal tubules of EG
      group and reduced in the EG + L group comparing to the control. In the EG + L
      group, the immunoreactivity of bcl-2 was increased in glomeruli. In EG + L
      treated group, number of caspase-3 immunopositive cells were decreased compared
      to all groups (P < 0.01). Apoptotic cells were increased in the EG-treated group
      compared to the other groups. Decreased apoptotic cell number was observed in the
      EG + L compared to the EG group (P < 0.01). Our findings suggest that losartan
      may provide a beneficial effect against tubulointerstitial damage and decrease
      renal tubular apoptosis caused by hyperoxaluria.

PMID- 20151117
TI  - Xanthogranulomatous pyelonephritis: an uncommon pediatric renal mass.
AB  - Xanthogranulomatous pyelonephritis (XGP) is a chronic suppurative infectious
      process that only rarely affects pediatric patients, and most commonly occurs in
      the setting of a large obstructing calculus. Histologically, XGP is characterized
      by the presence of chronic inflammation and lipid-laden macrophages. This case
      report illustrates the radiological, surgical, and pathologic findings in a young
      patient who presented to our institution for treatment of this uncommon
      condition. Although rare, xanthogranulomatous pyelonephritis is a clinically
      important entity that can affect pediatric patients. This condition should be
      considered in the differential diagnosis for an atypical-appearing renal mass.

PMID- 20151118
TI  - Pericallosal lipoma and middle cerebral artery aneurysm: a coincidence?
AB  - Intracranial lipomas are rare congenital malformations that can often be seen in
      association with other brain malformations; agenesis or dysgenesis of the corpus
      callosum is the most frequently associated brain anomaly. They are usually
      pericallosal asymptomatic midline lesions. Intracranial lipomas associated with a
      non-contiguous cerebral aneurysm are extremely rare. We report an infant with
      partial agenesis of the corpus callosum and pericallosal lipoma associated with
      cerebral haemorrhage due to a distal middle cerebral artery aneurysm. Such an
      association is probably not fortuitous and could suggest a pathogenic
      relationship.

PMID- 20151119
TI  - Abdominal manifestations of polyarteritis nodosa demonstrated with CT.
AB  - We report a rare case of polyarteritis nodosa (PAN) presenting in childhood. The
      child had multiple visceral aneurysms and later developed ascending colitis and
      jejunitis. The diagnosis was established with multidetector CT and CT
      angiography.

PMID- 20151120
TI  - Rhesus macaque MHC class I molecules show differential subcellular localizations.
AB  - The MHC class I gene family of rhesus macaques is characterised by considerable
      gene duplications. While a HLA-C-orthologous gene is absent, the Mamu-A and in
      particular the Mamu-B genes have expanded, giving rise to plastic haplotypes with
      differential gene content. Although some of the rhesus macaque MHC class I genes
      are known to be associated with susceptibility/resistance to infectious diseases,
      the functional significance of duplicated Mamu-A and Mamu-B genes and the
      expression pattern of their encoded proteins are largely unknown. Here, we
      present data of the subcellular localization of AcGFP-tagged Mamu-A and Mamu-B
      molecules. We found strong cell surface and low intracellular expression for Mamu
      A1, Mamu-A2 and Mamu-A3-encoded molecules as well as for Mamu-B*01704, Mamu
      B*02101, Mamu-B*04801, Mamu-B*06002 and Mamu-B*13401. In contrast, weak cell
      surface and strong intracellular expression was seen for Mamu-A4*1403, Mamu
      B*01202, Mamu-B*02804, Mamu-B*03002, Mamu-B*05704, Mamu-I*010201 and Mamu-I*0121.
      The different expression patterns were assigned to the antigen-binding alpha1 and
      alpha2 domains, suggesting failure of peptide binding is responsible for
      retaining 'intracellular' Mamu class I molecules in the endoplasmic reticulum.
      These findings indicate a diverse functional role of the duplicated rhesus
      macaque MHC class I genes.

PMID- 20151121
TI  - Primary cutaneous Ewing's sarcoma/primitive neuroectodermal tumor manifesting
      numerous small and huge ulcerated masses: its complete remission by chemotherapy
      and magnetic resonance imaging findings.
AB  - Extraskeletal Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET) are
      widely regarded as clinically and histologically identical tumors which consist
      of small blue round cells. Extraskeletal ESs/PNETs usually occur in the deep soft
      tissues of the paraspinal region, chest wall, or lower extremities. However,
      superficially located cases, so-called cutaneous ESs/PNETs, are exceedingly rare,
      and the vast majority of the reported cases present as a single small mass. We
      present magnetic resonance imaging (MRI) findings and clinical course of a unique
      case of primary cutaneous ES/PNET presenting as numerous huge masses with severe
      ulceration on them.

PMID- 20151122
TI  - To the editor: Long-term follow-up of patients with metastatic differentiated
      thyroid carcinoma.

PMID- 20151123
TI  - The gap between evidence-based guidelines and daily practice.

PMID- 20151124
TI  - Lipoblastoma: clinical features, treatment, and outcome.
AB  - BACKGROUND: Lipoblastoma is a rare, benign, encapsulated tumor arising from
      embryonic white fat. On histology they typically contain variably differentiated
      adipocytes, primitive mesenchymal cells, myxoid matrix, and fibrous trabeculae.
      The tumor occurs primarily in infancy and early childhood. It often occurs in the
      extremities and trunk, and rarely develops in the head and neck and other sites.
      METHODS: Ten cases of histopathologically proven lipoblastoma presenting to our
      hospital during a 6-year period (2003-2008) were reviewed retrospectively for
      their clinical presentations, treatment, postoperative outcome, and follow-up.
      RESULTS: There were five males and five females ranging in age from 6 months to
      20 years. The commonest presentation was a painless rapidly growing mass. Tumors
      occurred in an extremity (n = 5), head and neck (n = 3), trunk (n = 1), and
      retroperitoneum (n = 1). Preoperative diagnosis was accurate in only one case.
      The largest tumor measuring 25-cm x 20-cm x 7-cm and weighing 1.9 kg was excised
      from the retroperitoneum. All patients underwent complete surgical excision.
      Patient follow-up period ranging from 9 to 76 months showed no recurrences and no
      metastases. CONCLUSIONS: Lipoblastoma behaves benignly, occurs in both
      superficial and deep sites, and occasionally attains large size. Complete
      surgical excision is the treatment of choice and long-term follow-up is required
      because there is a reported tendency for these tumors to recur.

PMID- 20151125
TI  - Platelet transfusion can be related to liver regeneration after living donor
      liver transplantation.
AB  - BACKGROUND: Although liver regeneration is a fundamental aspect of living donor
      liver transplantation (LDLT), the factors that affect liver regeneration during
      the early post-transplantation period have not been thoroughly investigated.
      Recently it was suggested that platelets contribute to liver regeneration. The
      aim of the present study was to identify the major factors that affect liver
      graft regeneration during the early post-transplantation period. MATERIALS AND
      METHODS: Eighty-seven right liver grafted, adult-to-adult LDLT patients were
      retrospectively analyzed. Liver regeneration was assessed by volumetry from
      computed tomographic (CT) scans obtained between the 9th and 11th postoperative
      days. The authors investigated relationships between clinical variables and liver
      graft regeneration rates, and they conducted multiple regression analysis on
      factors found to be significant by univariate analysis. RESULTS: Mean graft
      weight at operation was 722.9 +/- 109.7 g, and mean graft volume assessed by
      follow-up CT was 1,042.2 +/- 155.6 ml, reflecting a mean liver graft regeneration
      of 45.9 +/- 22.3%. The graft regeneration was found to correlate inversely with
      graft-to-recipient weight ratio (GRWR, r = -0.406, p < 0.001) and directly with
      portal flow velocity (cm/s; r = 0.307; p = 0.004) and splenic index (cm(3); r =
      0.282; p = 0.009). Moreover, the total amount (units) of platelets transfused was
      found to be significantly associated with graft regeneration (r = 0.293; p = 
      .006). Stepwise regression analysis showed that GRWR (beta = -33.124; p = 0.001),
      total amount of platelets transfused (beta = 0.771; p = 0.012), and splenic index
      (beta = -0.010; p = 0.049) were independently associated with graft regeneration.
      CONCLUSIONS: The results of the present study suggest that platelets play a
      significant role in human liver regeneration after LDLT.

PMID- 20151126
TI  - Risk factors for early postoperative small bowel obstruction after colectomy for
      colorectal cancer.
AB  - BACKGROUND: Small bowel obstruction (SBO) after colectomy leads to markedly lower
      patient quality of life, longer hospital stays, and increased hospitalization
      costs. From a systemic treatment point of view, early postoperative SBO is one of
      the major concerns of the surgery because it often delays chemotherapy in
      advanced cases. The goal of this single-center study was to evaluate the risk
      factors for early postoperative SBO. METHODS: Univariate and multivariate
      analyses were performed for 1,004 patients who underwent open colectomy (OC, 421
      patients) or laparoscopic-assisted colectomy (LAC, 583 patients) for colorectal
      cancer between January 1997 and December 2008. RESULTS: The overall early
      postoperative SBO were 45 cases (4.5%). Univariate analysis of the risk factors
      for early postoperative SBO showed no statistical significance between respective
      risk factors and occurrence of SBO for age >70 years, body mass index >25
      kg/m(2), ASA score > or =3, pT stage T4, pN stage > or =N1, pM stage M1, or
      increased blood loss. Multivariate analysis demonstrated that OC (odds ratio
      (OR), 2.62; 95% confidence interval (CI), 1.34-5.13; P = 0.005), and rectal
      cancer (OR, 2.12; 95% CI, 1.1-4.1; P = 0.025) were independent risk factors for
      postoperative SBO after colectomy for colorectal cancer. Regarding the causes of
      SBO, paralytic obstruction was more frequent in the LAC group, and adhesive
      obstruction was more frequent in the OC group. CONCLUSIONS: Early postoperative
      SBO cases are more likely to occur with OC and rectal cancer. LAC is an effective
      surgical procedure from the perspective of reducing the incidence of early
      postoperative SBO after colectomy for colorectal cancer.

PMID- 20151127
TI  - Testicular and paratesticular pathology in children: a 12-year histopathological
      review.
AB  - BACKGROUND: Our institution is the principal pediatric surgical referral center
      for a population of 1.6 million. The objective of this study was to determine the
      spectrum and incidence of pediatric testicular and paratesticular pathology in
      this population. METHODS: Pathology results of all testicular and paratesticular
      specimens between August 1995 to September 2007 were analyzed. Clinical details
      were retrieved retrospectively from the computerized database, recording age,
      mode of presentation, laterality, and associated inguinoscrotal pathology.
      RESULTS: Over 12 years 2 months, 474 patients (502 specimens) were identified.
      Testicular and paratesticular pathology was most frequent in patients aged 1-2
      years (11%) and 11-12 years (10.5%). In all, 442 patients had non-neoplastic
      pathology, with 60.4% presenting acutely. The most common non-neoplastic
      pathologies were hydatid of Morgagni (42.6%) and "vanishing testis" (14.3%).
      Vanishing and atrophic testes were frequently explored between 1 and 2 years of
      age, with a left predominance. Most atrophic testes were undescended (54.8%).
      Testicular torsion occurred in 11.2%, with bimodal peak ages of <1 year and 13-14
      years. Interestingly, testicular torsion also occurred more on the left side
      (68%). A total of 32 patients had neoplasms. Of 27 patients with testicular
      neoplasms, 55.6% were malignant (29.6% primary and 26% secondary), the principal
      primary malignancy was yolk sac tumor; the most common benign neoplasms were
      epidermoid cysts and teratomas. Five patients had paratesticular neoplasms, with
      rhabdomyosarcoma in 80%. CONCLUSIONS: The variety of scrotal and testicular
      pathology in children is considerable, with acute pathologic conditions
      comprising the bulk in the older (7-15 years) children, whereas impalpable testes
      and neoplasms comprise most of the lesions in infants. Interestingly testicular
      torsion, vanishing testes, and atrophic testes occur mainly on the left side.
      Benign testicular neoplasms occur more frequently than primary malignancies.

PMID- 20151128
TI  - LigaSure for pancreatic sealing during distal pancreatectomy.
AB  - BACKGROUND: Pancreatic fistula is an unresolved problem after distal
      pancreatectomy. The current study investigated the safety of LigaSure for distal
      pancreatic resection in a porcine model. METHODS: A distal pancreatectomy was
      performed in 22 pigs. Animals were randomly assigned to undergo conventional
      scalpel transection with hand-sewn closure of the pancreatic remnant or
      pancreatic transection and sealing by LigaSure. Closed-suction drainage was
      collected daily. Animals were sacrificed on postoperative day (POD) 7 and the
      pancreatic remnant was sampled for histology. RESULTS: Two grade A postoperative
      temporary pancreatic fistulas (ISGPF definition) developed after hand suturing
      but none after LigaSure sealing. Amylase and lipase levels in drainage fluid were
      higher in the suture group during the first postoperative days but showed no
      differences after the fourth day. All but two animals that had to be euthanized
      because of small bowel invagination survived until POD 7. No significant
      differences were found in macroscopic changes between groups at reexploration.
      Histology demonstrated focal, chronic granulating inflammation with minor
      necrosis in all animals. CONCLUSIONS: The LigaSure sealing device provides a safe
      alternative to conventional hand-sewn closure of the pancreatic stump in distal
      pancreatectomy. This is the first study that investigated this effective and
      highly applicable technique for pancreatic transection.

PMID- 20151129
TI  - Effect of dexamethasone on postoperative symptoms in patients undergoing elective
      laparoscopic cholecystectomy: randomized clinical trial.
AB  - BACKGROUND: Dexamethasone has been reported to reduce postoperative nausea and
      vomiting (PONV) after laparoscopic cholecystectomy (LC). However, its effects on
      other surgical outcomes, such as pain and fatigue, have been unclear. We
      evaluated the efficacy of preoperative dexamethasone for ameliorating
      postoperative symptoms after LC. METHODS: In this prospective, double-blind,
      placebo-controlled study, 210 patients scheduled for elective LC were analyzed
      after randomization to intravenous dexamethasone (8 mg) or a placebo. All
      patients underwent standardized procedures for general anesthesia and surgery.
      Episodes of PONV and the pain and fatigue scores were recorded on a visual analog
      scale. Analgesic and antiemetic requirements were also recorded. RESULTS: There
      were no significant differences between groups with regard to medical or
      demographic variables. Significantly fewer patients experienced PONV in the
      dexamethasone group immediately after LC and at 6 and 12 h. The need for
      ondansetron to relieve PONV was higher in the placebo group (P = 0.001). Patients
      in the study group reported less postoperative pain during the first 24 h and
      less fatigue after 6, 12, and 24 h. The need for buprenorphine to relieve
      intolerable pain was also less in this group (P = 0.009). There were no side
      effects, and the morbidity was similar in the two groups (6.7 vs. 7.6%).
      CONCLUSIONS: The regimen we employed is safe and without apparent side effects.
      Thus, preoperative dexamethasone can significantly reduce the incidence of PONV,
      pain and fatigue after elective LC.

PMID- 20151130
TI  - Predictors of mortality in skin and soft-tissue infections caused by Vibrio
      vulnificus.
AB  - BACKGROUND: Vibrio vulnificus infection can progress rapidly in skin or soft
      tissue, and it is potentially life-threatening. The purpose of the present study
      was to explore the predictors of mortality in patients with V. vulnificus
      infections of skin or soft tissue. METHODS: The medical records of 119
      consecutive patients aged > or =18 years, hospitalized for V. vulnificus
      infections of skin or soft tissue between January 2000 and December 2007 were
      reviewed. Co-morbidities, clinical manifestations, laboratory studies,
      treatments, and outcomes were analyzed. Multiple logistic regression with the
      exact method was performed. RESULTS: The mean age of the patients was 63.7 +/-
      12.0 years. Twenty-four patients died, yielding an overall case fatality rate of
      20%. Of the 24 deaths, 20 (83%) occurred within 72 h after hospital admission. Of
      119 patients, 45 patients had primary septicemia, and 74 patients had wound
      infection. Multivariate analysis revealed that the following factors were
      associated with mortality: hemorrhagic bullous skin lesions/necrotizing fasciitis
      (p = 0.003), primary septicemia (p = 0.042), a greater organ dysfunction and/or
      infection score (p = 0.005), absence of leukocytosis (p = 0.0001), and
      hypoalbuminemia (p = 0.003). Treatment with surgical intervention plus
      antibiotics (p = 0.038) and surgical intervention within 24 h after admission (p
      = 0.017) were protective factors. CONCLUSIONS: This study demonstrates that the
      presence of hemorrhagic bullous skin lesions/necrotizing fasciitis, primary
      septicemia, a greater severity-of-illness, absence of leukocytosis, and
      hypoalbuminemia were the significant risk factors for mortality in these
      patients. Moreover, patients treated with surgery plus antibiotics, especially
      those receiving a prompt surgical evaluation within 24 h after hospital
      admission, may have a better prognosis.

PMID- 20151131
TI  - Opportunities and improvisations: a pediatric surgeon's suggestions for
      successful short-term surgical volunteer work in resource-poor areas.
AB  - There is a paucity of trained pediatric surgeons in resource-poor areas, and many
      children never receive care for debilitating problems that could readily be
      managed by surgeons with proper training, supplies, and instrumentation. This
      article, written from the perspective of a surgeon who has been both the
      recipient of and the provider of volunteer surgical services, is intended to
      encourage surgeons in technologically advanced locations to volunteer in
      underserved areas and to assist them in the implementation of such endeavors.
      Concepts are presented with an emphasis on pediatric surgery, but most are
      relevant for volunteers in all surgical specialties. Volunteer paradigms include,
      but are not limited to, the "surgical brigade" model, where a large group of
      health care professionals take all needed equipment and supplies for the duration
      of their stint, and the "minimalist" model, where a single volunteer works with
      local personnel using locally available equipment. For a successful volunteer
      endeavor the host needs to have a perceived need for the volunteer's services,
      and the volunteer must be flexible in adapting to meet overwhelming needs with
      limited resources. It is suggested that appropriate technology, such as the
      inexpensive anal stimulator presented herein, should be employed whenever
      possible. With proper planning, realistic expectations, and a cooperative and
      helpful attitude, volunteer trips can be rewarding experiences for both
      volunteers and host physicians and lead to lasting relationships that improve
      children's lives globally.

PMID- 20151132
TI  - The effect of obstruction and perforation on colorectal cancer disease-free
      survival.
AB  - BACKGROUND: Obstruction (OBSTR) and perforation (PERF) in colorectal cancer
      impact adversely upon outcomes, and cancer-related survival may also be affected.
      However, data are sparse, particularly on disease-free survival (DFS) where the
      cancer is both obstructed and perforated (OBS-PERF). METHODS: Data were extracted
      from a prospectively collected database of 1876 colorectal cancer patients
      managed and followed up at the Royal Brisbane Hospital from 1984 to 2004. The
      patients who had curative surgery (n = 1426) were classified as OBSTR (n = 153),
      PERF (n = 53), OBS-PERF (n = 19), and uncomplicated (UNCOM; n = 1201). Kaplan
      Meier survival and Cox proportional hazard analyses were performed. RESULTS:
      Postoperative mortality within 30 days of surgery was 1.5% (n = 22) and the
      overall complication rate was 40.8% (n = 582). However, only 7.2% (n = 102)
      required reoperations. The median survival time was 71 (IQR = 64.9-77.1) months
      and the median follow-up for DFS was 37.5 (IQR 14-68) months. The overall
      recurrence rate was 32.7% (n = 466), the local recurrence rate was 9.4% (n =
      135), and local and distant recurrences occurred in the same patient in 4.7% (n =
      67). Male gender, OBSTR, PERF, OBS-PERF, emergency operation, major medical and
      surgical complications, reoperation, TNM staging, tumor grading, and tumor venous
      invasion adversely affected DFS (p < 0.05). Multivariate analysis showed that OBS
      PERF (p = 0.008), major medical complications (p = 0.011), reoperation (p =
      0.018), TNM staging (p < 0.001), grading (p = 0.018), and venous invasion (p =
      0.002) were independently associated with a poorer DFS. CONCLUSIONS: OBS-PERF
      colorectal cancer is associated with a poorer DFS, which may be worse than either
      OBSTR or PERF alone.

PMID- 20151133
TI  - Dexamethasone in patients undergoing elective laparoscopic cholecystectomy
      improves postoperative symptoms.

PMID- 20151134
TI  - Do basic psychomotor skills transfer between different image-based procedures?
AB  - BACKGROUND: Surgical techniques that draw from multiple types of image-based
      procedures (IBP) are increasing, such as Natural Orifice Transluminal Endoscopic
      Surgery, fusing laparoscopy and flexible endoscopy. However, little is known
      about the relation between psychomotor skills for performing different types of
      IBP. For example, do basic psychomotor colonoscopy and laparoscopy skills
      interact? METHODS: Following a cross-over study design, 29 naive endoscopists
      were trained on the Simbionix GI Mentor and the SimSurgery SEP simulators. Group
      C (n = 15) commenced with a laparoscopy session, followed by four colonoscopy
      sessions and a second laparoscopy session. Group L (n = 14) started with a
      colonoscopy session, followed by four laparoscopy sessions and a second
      colonoscopy session. RESULTS: No significant differences were found between the
      performances of group L and group C in their first training sessions on either
      technique. With additional colonoscopy training, group C outperformed group L in
      the second laparoscopy training session on the camera navigation task.
      CONCLUSIONS: Overall, training in the basic colonoscopy tasks does not affect
      performance of basic laparoscopy tasks (and vice versa). However, to limited
      extent, training of basic psychomotor skills for colonoscopy do appear to
      contribute to the performance of angled laparoscope navigation tasks. Thus,
      training and assessment of IBP type-specific skills should focus on each type of
      tasks independently. Future research should further investigate the influence of
      psychometric abilities on the performance of IBP and the transfer of skills for
      physicians who are experienced in one IBP type and would like to become
      proficient in another type of IBP.

PMID- 20151136
TI  - Posterior reversible encephalopathy syndrome occurring after uterine artery
      embolization for uterine myoma.
AB  - This case report describes posterior reversible encephalopathy syndrome (PRES)
      occurring after uterine artery embolization (UAE) for uterine myoma. This is the
      first report of PRES occurring after uterine vascular radiologic intervention.
      The mechanism by which UAE induced PRES is unclear.

PMID- 20151137
TI  - MDCT-guided transthoracic needle aspiration biopsy of the lung using the
      transscapular approach.
AB  - The purpose of this study is to report our preliminary experience using MDCT
      guided percutaneous transthoracic needle aspiration biopsy using the
      transscapular approach in the upper posterolateral lung nodules, an area that it
      is difficult or hazardous to reach with the conventional approach. Five patients
      underwent CT-guided percutaneous transthoracic needle aspiration biopsy of the
      lung via the transscapular approach. A coaxial needle technique was used in all
      patients. Biopsy was successful in all patients. No major complications were
      encountered. One patient developed a minimal pneumothorax next to the lesion
      immediately after biopsy, which resolved spontaneously. MDCT-guided percutaneous
      transthoracic needle aspiration biopsy of the lung via the transscapular approach
      is an effective and safe procedure that reduces the risk of pneumothorax in
      selected patients.

PMID- 20151138
TI  - Quality improvement guidelines for bone tumour management.

PMID- 20151140
TI  - Mid-term follow-up after retrograde recanalization of chronically occluded
      saphenous vein graft.
AB  - We reported a case of 55-year-old male with an ostial chronically occluded
      saphenous vein graft which was recanalized by retrograde approach through an
      epicardial collateral channel with implantation of three drug eluting stents. Six
      month coronary angiography showed the patency of graft and distal native vessel
      diameter enhancement.

PMID- 20151141
TI  - Quantitation of the thickness of the non-enhanced myocardial rim predicts
      recovery of territorial myocardial function in chronic ischemic heart disease: a
      cardiac magnetic resonance imaging study.
AB  - OBJECTIVES: We sought to determine whether the thickness of the non-contrast
      enhanced myocardial rim (RIM) predicts recovery of territorial myocardial
      function after revascularization in chronic ischemic cardiomyopathy (ICM).
      BACKGROUND: Non-contrast-enhanced dysfunctional myocardium at late gadolinium
      enhanced CMR depicts the presence of viable myocardium. METHODS: In 29 patients
      (65 +/- 8 years) with ICM (EF 33 +/- 10), ceCMR and cine images were acquired 5
      +/- 10 days before revascularization. Cine images were repeated after 6 months.
      Regional wall thickness, wall thickening and RIM were determined in each of 12
      segments per short-axis slice (4-8/patient), which were assigned to the
      respective supplying coronary artery (LAD, LCX and RCA). A threshold for normal
      wall-thickening was derived from a control group (n = 14; 52 +/- 17 years).
      Functional improvement at follow-up was defined as wall thickening >2 mm.
      RESULTS: Of the 1,896 analyzed segments, 655 segments showed severe dysfunction.
      At follow-up, 307 segments demonstrated functional improvement. The RIM differed
      between segments with and without improvement (6.6 +/- 2.4 mm vs. 2.8 +/- 2.0 mm;
      p < 0.0001). The area under the receiver operator characteristic (ROC) for
      predicting overall functional recovery was 0.91 (95%, CI 0.88-0.93, p < 0.001). A
      RIM of 4.0 mm predicted functional recovery after revascularization of the
      supplying coronary artery with a sensitivity and a specificity of 88 and 82% for
      the LAD, 96 and 86% for the RCA and 88 and 83% for the LCX, respectively.
      CONCLUSION: RIM may be a useful marker for predicting territorial functional
      recovery after revascularization in patients with chronic ICM.

PMID- 20151142
TI  - Effects of short-term maternal fasting in the third trimester of pregnancy on
      fetal biophysical profile and Doppler indices scores.
AB  - INTRODUCTION: It was aimed to investigate the effects of short-term maternal
      fasting on fetal biophysical profile (BPP) scores and obstetric doppler indices.
      MATERIALS AND METHODS: Thirty healthy uncomplicated singleton pregnancy cases
      were enrolled into the study. RESULTS AND CONCLUSION: Fasting decreased BPP
      reversibly, but not to a level below 8/10. AFI, umbilical and MCA impedances were
      unchanged while pulsatility, resistance and systolic/diastolic values of uterine
      arteries were increased.

PMID- 20151143
TI  - Minichromosome stability induced by partial genome duplication in Arabidopsis
      thaliana.
AB  - Two partially reconstructed karyotypes (RK1 and RK2) of Arabidopsis thaliana have
      been established from a transformant, in which four structurally changed
      chromosomes (alpha, beta, gamma, and delta) were involved. Both karyotypes are
      composed of 12 chromosomes, 2n = 1" + 3" + 4" + 5" + alpha" + gamma" = 12 for RK1
      and 2n = 3" + 4" + 5" + alpha" + beta" + gamma" = 12 for RK2, and these
      chromosome constitutions were relatively stable at least for three generations.
      Pairing at meiosis was limited to the homologues (1, 3, 4, 5, alpha, beta, or
      gamma), and no pairing occurred among non-homologous chromosomes in both
      karyotypes. For minichromosome alpha (mini alpha), precocious separation at
      metaphase I was frequently observed in RK2, as found for other minichromosomes,
      but was rare in RK1. This stable paring of mini alpha was possibly caused by
      duplication of the terminal tip of chromosome 1 that is characteristic of RK1.

PMID- 20151144
TI  - Reaction patterns of pulmonary macrophages in protracted asphyxiation.
AB  - Do long periods of asphyxiation trigger the proliferation of pulmonary
      macrophages and the formation of giant cells? Three groups have been defined: six
      autopsy cases with time periods of suffocation >25 min (long protracted
      asphyxiation), eight cases with estimated time periods of suffocation 10-25 min
      (short protracted asphyxiation) and nine cases where death had occurred
      immediately (very severe trauma). The stain used was haematoxylin and eosin
      (H&E), and the immunohistochemical stainings were performed using antibodies CD
      68, MRP 8, MRP 14 and NP 57. The intraalveolar macrophages and giant cells were
      counted in H&E sections. For the immunohistochemical stainings, a scoring was
      used in order to compare the groups. In protracted asphyxiation, the number of
      intraalveolar macrophages was definitely elevated. A significant increase of
      giant cells was observed in the cases of long protracted asphyxiation. CD 68
      showed clearly elevated numbers in both asphyxiation groups. Early-stage
      macrophages are significantly increased in protracted asphyxiation. With
      increasing time periods of asphyxiation, the results become more significant. The
      results show that the length of the agony period stimulates the proliferation of
      pulmonary macrophages and the formation of giant cells.

PMID- 20151145
TI  - Validating population-based registers for ALS: how accurate is death
      certification?
AB  - The purpose of this study was to determine the accuracy of death certification
      for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) as recorded by
      the Central Statistics Office in the Republic of Ireland, and to examine its
      utility in capture-recapture analysis. The database of the Irish Central
      Statistics Office (CSO) was searched for death certificates of individuals over
      15 years of age for whom ALS/MND (ICD9) was listed as a primary, secondary or
      tertiary cause of death from 2002 to 2006. This dataset was compared with
      mortality data from the Irish Register for ALS/MND for the same period. Three
      hundred ninety-eight cases with a diagnosis of ALS were identified through the
      CSO. The cause of death as identified by the CSO was 318 out of 398 (80%) cases
      known to the Register during the study period. ALS/MND was listed as a cause of
      death by the CSO in 79 (20%) cases that were unknown to the ALS/MND Register. Of
      these, ALS/MND was listed as a secondary/tertiary cause of death in 76, and 75%
      of all such deaths occurred in rural areas. Capture-recapture analysis using the
      CSO and ALS Register as independent datasets generated a likely over-estimation
      of the crude incidence of ALS from 2.1/100,000 to 3.45/100,000 in Ireland.
      Population-based registers are most accurate when ascertaining from a wide
      network of inter-dependent sources. Death certification for ALS/MND lacks both
      sensitivity and specificity. Capture-recapture exercises using such data sources
      are likely to over-estimate the true incidence of disease.

PMID- 20151146
TI  - Having the vision to measure calcium.

PMID- 20151147
TI  - Improbable effect of carbohydrate diet on cardiac autonomic modulation during
      exercise.

PMID- 20151148
TI  - Reticulocyte profile in top-level alpine skiers during four consecutive
      competitive seasons.
AB  - The role of reticulocytes (Ret) in sports medicine became clear when the count of
      immature erythrocytes was introduced in protocols used for anti-doping purposes.
      Because specific research regarding seasonal variations in Ret is lacking, we
      assessed Ret (and [Hb]) in top-level male and female skiers during four
      consecutive competitive seasons. A difference (P < 0.05) between males and
      females was found for [Hb] and Ret values: [Hb] was lower and Ret was higher in
      females. The difference was maintained across all four competitive seasons.
      Marked within-subject differences in [Hb], Ret and immature reticulocyte fraction
      values were noted; the within-subject variability was greater than the between
      subject variability in both genders. For instance, a difference for Ret was
      consistently shown between first and second blood drawings, i.e. between basal
      value, before the start of training and competition, and the value at middle of
      season, when training workload was at highest level. Unlike Ret%, the analysis of
      variance showed significant changes in [Hb] values across competitive seasons for
      both genders. Comparison between consecutive seasons (e.g., 2005-2006 vs. 2006
      2007) showed significant differences for both parameters. The behaviour of [Hb]
      and Ret during the various seasons was parallel in females, whereas a discrepancy
      existed in males. In general, inter-individual variability is quite high, thus,
      Ret and [Hb] modifications should be referred only to the single athlete. We
      confirm the validity of the use of Ret counts for anti-doping purposes.

PMID- 20151149
TI  - Metabolic rate and gross efficiency at high work rates in world class and
      national level sprint skiers.
AB  - The present study investigated metabolic rate (MR) and gross efficiency (GE) at
      moderate and high work rates, and the relationships to gross kinematics and
      physical characteristics in elite cross-country skiers. Eight world class (WC)
      and eight national level (NL) male sprint cross-country skiers performed three 5
      min stages using the skating G3 technique, whilst roller skiing on a treadmill.
      GE was calculated by dividing work rate by MR. Work rate was calculated as the
      sum of power against gravity and frictional rolling forces. MR was calculated
      using gas exchange and blood lactate values. Gross kinematics, i.e. cycle length
      (CL) and cycle rate (CR) were measured by video analysis. Furthermore, the skiers
      were tested for time to exhaustion (TTE), peak oxygen uptake (VO(2peak)), and
      maximal speed (V(max)) on the treadmill, and maximal strength in the laboratory.
      Individual performance level in sprint skating was determined by FIS points. WC
      skiers did not differ in aerobic MR, but showed lower anaerobic MR and higher GE
      than NL skiers at a given speed (all P < 0.05). Moreover, WC skiers skated with
      longer CL and had higher V(max) and TTE (all P < 0.05). In conclusion, the
      present study shows that WC skiers are more efficient than NL skiers, and it is
      proposed that this might be due to a better technique and to technique-specific
      power.

PMID- 20151150
TI  - Expression and prognostic significance of focal adhesion kinase in hepatocellular
      carcinoma.
AB  - AIM: To examine the expressions of focal adhesion kinase (FAK) and its clinical
      significance in hepatocellular carcinoma (HCC). METHODS: We determined the
      expression levels of FAK on both steady-state mRNA and protein levels in 50 HCC
      samples by quantitative real-time PCR and immunohistochemistry, respectively. The
      correlations between FAK expression and various clinicopathological parameters
      were analyzed. RESULTS: The expression of FAK on the mRNA level was consistent
      with that on the protein level. FAK mRNA levels in tumor tissues were
      significantly higher than in the paratumor tissues (0.229 +/- 0.027 vs. 0.163 +/-
      0.019; P < 0.001), but lower than in the macroscopic cancer emboli (0.506 +/-
      0.155 vs. 0.377 +/- 0.176; P < 0.05). Compared within the tumor tissues, FAK
      expressions were significantly higher in those with cancer emboli than those
      without (0.343 +/- 0.05 vs. 0.165 +/- 0.025; P = 0.003). Univariate and
      multivariate analyses revealed that FAK expression was an independent prognostic
      factor for disease-free survival and overall survival. Both 3-year disease-free
      survival rates and overall survival rates in FAK-negative group were
      significantly higher than in positive group (52 vs. 20% and 72 vs. 29%, P <
      0.001). CONCLUSION: Our results suggest that FAK expression is up-regulated in
      HCC and its expression is an independent prognostic factor for HCC.

PMID- 20151152
TI  - Identification of aberrant promoter hypomethylation of HOXA10 in ovarian cancer.
AB  - PURPOSE: The purpose of this study was to determine the relationship between
      hypomethylation of HOXA10 gene's promoter and high expression in malignant
      ovarian tissues, and to confirm the level of hypomethylation in ovarian cell
      lines. EXPERIMENTAL DESIGN: We performed the methylation status of 29 samples
      from ovarian carcinomas and 16 from normal tissues by methylation-specific
      polymerase chain reaction (MSP). Then, we evaluated the expression of mRNA and
      protein of HOXA10 in all samples to work out the relationship between the
      methylation status of HOXA10 and its expression in transcriptional and
      translational levels. We then confirmed our present study using SKOV3 and HEY
      ovarian cancer cell lines treated with the demethylating agent 5-aza-2'
      deoxycytidine (5-aza-dC) to detect whether the expression of HoxA10 in the two
      cell lines was altered. RESULTS: Increased expression of HOXA10 was detected in
      almost all ovarian carcinomas (p < 0.05). Promoter hypomethylation was found in
      (17 of 29) 58.62% ovarian cancers and (4 of 16) 25% normal ovaries (p < 0.05).
      The HOXA10 expression is higher when the status of HOXA10 gene promoter is
      hypomethylated than in methylated tissues (p < 0.05). After 5-aza-dC treatment,
      the expression level of HOXA10 mRNA transcript was increased in the two cell
      lines. CONCLUSION: Our results indicate that promoter hypomethylation is an
      important mechanism for high expression of HOXA10 in human ovarian cancer and may
      be a potential prognostic factor in ovarian cancer.

PMID- 20151151
TI  - Altered expression of p120catenin predicts poor outcome in invasive breast
      cancer.
AB  - PURPOSE: The study focuses on p120catenin, a regulator of cell adhesion, which
      has previously been described in many malignancies and suggested with a role in
      invasion and metastatic behaviour. In this study, we investigate the role of
      altered immunoexpression of p120catenin isoforms in the prognosis of invasive
      breast cancer (n = 351). METHODS: We used cDNA microarrays to screen differences
      in gene expression in invasive breast cancer in general, and between local and
      metastasized disease particularly. On this basis, we performed p120catenin
      immunohistochemistry in order to confirm the prognostic value of p120catenin
      isoforms on tissue microarrays comprising 341 patients from the era of
      mammographic screening, directed to modern surgical and oncological treatments,
      and followed-up for maximum of 20 years. RESULTS: In cDNA microarray analysis,
      p120catenin was discovered down-regulated along with E-cadherin and alpha
      catenin. In addition, p120catenin distinguished metastasized breast cancer from
      local disease. Immunohistochemistry confirmed the value of p120catenin as an
      independent prognosticator of breast cancer survival. In our results, p120catenin
      was associated with 3.7-fold risk of breast cancer death in multivariate Cox's
      regression analyses adjusted for the established prognosticators of breast cancer
      (p = 0.039). Particularly, the long isoform of p120catenin predicted metastatic
      disease (p = 0.029). CONCLUSION: The present paper is the first report on
      p120catenin in invasive breast cancer based on a well-characterized patient
      material with long-term follow-up. We observed altered expression of p120catenin
      isoforms in invasive breast cancer and, in our material, the decrease in p120
      immunoexpression was significantly associated with poor outcome of disease.

PMID- 20151153
TI  - Proliferating cell nuclear antigen in gonad and associated storage tissue of the
      Pacific oyster Crassostrea gigas: seasonal immunodetection and expression in
      laser microdissected tissues.
AB  - To understand the processes involved in tissue remodeling associated with the
      seasonal reproductive cycle of the oyster Crassostrea gigas, we used
      immunodetection and expression measurements of proliferating cell nuclear antigen
      (PCNA). The expression of the PCNA gene was measured by real-time polymerase
      chain reaction in the whole gonadal area compared with laser microdissected gonad
      and storage tissue. Results underlined the advantage of the laser microdissection
      approach to detect expression, mainly for early stages of spermatogenesis. In the
      storage tissue, PCNA expression was reduced in the gonadal tubules, but
      immunolabeled hemocytes and vesicular cells were detected when the storage tissue
      was being restored. In the gonadal tubules, the PCNA gene was more highly
      expressed in males than in females. As soon as spermatogenesis was initiated,
      PCNA expression showed a high and constant level. In females, the expression
      level increased gradually until the ripe stage. The immunological approach
      established the involvement of peritubular cells in gonadal tubule expansion
      during early gametogenesis. In both sexes, gonial mitosis was immunodetected
      throughout the reproductive cycle. In males, the occurrence of two types of
      spermatogonia was ascertained by differential immunolabeling, and intragonadal
      somatic cell proliferation was noted. As expected, immunolabeling was never
      observed from stage II spermatocytes to spermatozoa. In females, positively
      stained cells were detected from oogonia to growing oocytes with various labeled
      intracellular locations.

PMID- 20151154
TI  - Multipotent neuroblasts generate a biochemical neuroarchitecture in the central
      complex of the grasshopper Schistocerca gregaria.
AB  - We have examined the developmental expression of the neuromodulators
      locustatachykinin, leucokinin-1, allatostatin and serotonin in a subset of
      lineages (Y, Z) of the central complex in the brain of the grasshopper
      Schistocerca gregaria. First, we show that all these neuromodulators are
      expressed in the same lineages during embryogenesis. The neuroblasts generating
      these lineages are therefore biochemically multipotent. Second, the neurons
      expressing the different neuromodulators are found clustered at stereotypic
      locations in their respective lineages. Locustatachykinin and leucokinin-1 map to
      the apical region of the lineage, allatostatin medially and serotonin to the base
      of the lineage. Since the location in these lineages translates into their birth
      order, we have been able ontogenetically to analyse their biochemical expression
      patterns. The age-profile within a lineage reveals that locustatachykinin- and
      leucokinin-1-expressing neurons are born first, then allatostatin neurons and
      finally serotoninergic neurons. Co-expression has been tested for serotonin with
      locustatachykin, leucokinin-1 or allatostatin and is negative but is positive for
      locustatachykinin and leucokinin-1, consistent with the stereotypic location of
      cells in the lineages. The delay between the birth of a neuron and the expression
      of its neuromodulator is stereotypic for each substance. Combined with a known
      birth date, this delay translates into a developmental expression pattern for the
      central complex itself.

PMID- 20151155
TI  - Habitat-mediated impact of alien mink predation on common frog densities in the
      outer archipelago of the Baltic Sea.
AB  - Alien predators have been recognised as one possible cause for amphibian declines
      around the world, but little is known of habitat-mediated predation impacts
      especially on adult amphibians. We studied common frog Rana temporaria under
      American mink Mustela vison predation in the outer archipelago of the Baltic Sea,
      south-western Finland. Using egg batches as an index of breeding frog female
      numbers we compared frog numbers and densities between a large, long-term mink
      removal area and a comparable control area. Frog numbers in the removal area were
      at least 2.7-fold higher than those in the control area. In the presence of mink,
      frog densities increased with the amount of vegetation cover on the islands,
      indicating that mink predation affected frog densities especially on less
      vegetated islands. An opposite trend appeared to be true for frogs in the mink
      removal area, where other predators like snakes could induce a decline of frog
      densities on more vegetated islands. Shrub or grass vegetation seems to provide
      frogs shelter against alien mink predation. Our result highlights the importance
      of landscape-level habitat management as a conservation tool for amphibian
      populations.

PMID- 20151156
TI  - Should I stay or should I go: predator- and conspecific-induced hatching in a
      marine snail.
AB  - Predator-induced hatching plasticity has been demonstrated in many species of
      amphibians. However, animals from other clades (e.g., marine species of molluscs
      and annelids) also place their embryos in capsules or gelatinous masses and might
      also exhibit hatching plasticity to predators. To date there is no evidence of
      predator-induced hatching plasticity from any marine species or a major clade of
      bilateria animals, the Lophotrochozoa. We studied predator-induced hatching
      plasticity of Nucella lamellosa, a carnivorous marine snail that deposits embryos
      in capsules. We used two experiments to investigate the effects of two types of
      predator, crabs and isopods, on developing embryos. In the first experiment, we
      quantified proportion of hatched embryos from capsules through time exposed to
      water-borne chemicals of crabs and isopods. Crabs delayed time-to-hatching, and
      the effects of predators were additive. In the second experiment, we quantified
      proportion of hatched embryos from capsules through time, developmental stage,
      and size of embryos in capsules exposed to water-borne chemicals of crabs and
      conspecifics. With this experiment, we wanted to answer: (1) whether a delay in
      hatching corresponded to embryos developing slower, and (2) whether the general
      products of metabolic waste from organisms can delay hatching. We unexpectedly
      observed that adult conspecific snails accelerated hatching but not developmental
      rate-the few past studies on the effects of conspecifics have all demonstrated
      that conspecifics delay time-to-hatching and rate of development. The results
      were also inconsistent with metabolic waste in general causing a delay in
      hatching, although the effect of conspecifics does weaken this inference. This
      study demonstrates that predators delay time-to-hatching in a marine mollusc, and
      suggests that predator-induced hatching plasticity is widespread among animals
      and likely evolved multiple times within the bilateria. In addition, conspecifics
      accelerated time-to-hatching in a marine mollusc, which suggests that
      conspecifics, like predators, might commonly influence when embryos hatch.

PMID- 20151157
TI  - New therapies: calcimimetics, phosphate binders and vitamin D receptor
      activators.
AB  - At present, new compounds are available to treat secondary hyperparathyroidism,
      namely calcimimetics, novel phosphorus binders and also novel vitamin D receptor
      activators. Calcimimetics increase the sensitivity of the parathyroid gland to
      calcium through spatial configurational changes of the calcium-sensing receptor.
      In addition, experimental studies have demonstrated that calcimimetics also
      upregulate both the calcium-sensing receptor and the vitamin D receptor. They are
      efficacious in children, though the experience in paediatric chronic kidney
      disease is still limited. Sevelamer, lanthanum carbonate and magnesium iron
      hydroxycarbonate are novel phosphorus binders available on the market. Several
      studies have demonstrated their efficacy and safety up to 6 years, though costs
      are the main limitation for a wider use. Since almost all the experience
      available on the new phosphorus binders comes from its use in adults, studies on
      children are needed in order to confirm the efficacy and safety of these
      products. Other new salts and polymers are also being developed. New vitamin D
      receptor activators, such as paricalcitol, are as effective at suppressing
      parathyroid hormone (PTH) as the traditional vitamin D receptor activators used
      for the past two decades, but they have a better and safer profile, showing fewer
      calcaemic and phosphoraemic effects while preserving the desirable effects of the
      vitamin D receptor activators on the cardiovascular system, hypertension,
      inflammation and fibrosis. Their use in children with chronic kidney disease has
      revealed similar responses to those of adults. The novel compounds discussed in
      this review should facilitate and improve the management of mineral and bone
      disorders in children with chronic kidney disease.

PMID- 20151158
TI  - A study on strategies for improving growth and body composition after renal
      transplantation.
AB  - Allograft function and metabolic effects of four treatment regimens, namely,
      methylprednisone (MP) standard dose (MP-STD), deflazacort (DFZ), MP-late steroid
      withdrawal (MP-LSW), and MP-very low dose (MP-VLD), were evaluated in prepubertal
      patients. MP was decreased by month 4 post-transplantation to 0.2 mg/kg/day in MP
      STD and DFZ patients and to <0.1 mg/kg/day in MP-LSW and MP-VLD patients.
      Starting in month 16 post-transplant, MP was switched to DFZ in the DFZ group and
      totally withdrawn in the MP-LSW group. Creatinine clearance diminished in the MP
      STD and MP-LSW groups from 77 +/- 6 to 63 +/- 6 ml/min/1.73 m(2)and from 103 +/-
      5 to 78 +/- 3 ml/min/1.73 m(2), respectively (p < 0.01 and p < 0.001,
      respectively). Height increased >0.5 SDS only in the MP-LSW and MP-VLD groups.
      The body mass index and fat body mass for height-age increased only in the MP-STD
      patients (p < 0.05 and p < 0.01, respectively). Fat body mass decreased in the
      DFZ group (p < 0.05), total cholesterol and LDL-cholesterol increased in the MP
      STD group, while LDL-cholesterol and total cholesterol/HDL-cholesterol ratio
      decreased in the DFZ group (p < 0.01). Lumbar spine bone mineral density (BMD)
      for height-age showed an increase in the MP-LSW and MP-VLD groups (p < 0.01). Our
      data suggest that MP-LSW and MP-VLD strategies improve linear growth, BMD, the
      peripheral distribution of fat, and preservation of the bone-muscle unit and
      maintain the normal lipid profile. The MP-LSW patients had a concerning rate of
      acute rejections and graft function deterioration in prepubertal patients.

PMID- 20151159
TI  - IgG subclasses and complement pathway in segmental and global membranous
      nephropathy.
AB  - The aim of our study was to clarify the association between immunoglobulin G(IgG)
      subclasses and the complement pathway in patients with idiopathic membranous
      nephropathy (MN). Immunofluorescence (IF) was performed in 16 MN patients and 20
      controls using antibodies against IgG, IgA, IgM, C1q, C3c, C4d, IgG1, IgG2, IgG3,
      IgG4, mannose binding lectin (MBL), C4-binding protein (C4-bp), factor B, C5b-9,
      and CD59. MN was classified into two types, segmental MN (S-MN; six patients) and
      global MN (G-MN; ten patients), according to the distribution of IgG deposits
      along the glomerular capillary wall. No deposition of any antibody was found in
      the controls. IF revealed IgG1, IgG3, C1q, C3c, C4d, C4-bp, C5b-9, and CD59
      deposits in patients with S-MN, whereas IgG1, IgG2, IgG3, IgG4, C3c, C4d, MBL,
      factor B, C4-bp, C5b-9, and CD59 deposits were detected in those with G-MN. There
      was a higher deposition of IG1, IgG2, and IgG4 in patients with G-MN than in
      those with S-MN, whereas the intensity of C1q deposits was higher in S-MN than in
      G-MN patients. In contrast, the intensity of factor B and MBL was higher in G-MN
      than in S-MN patients. This is the first report of S-MN patients showing
      complement activation of the classical pathway associated with IgG1 and IgG3 and
      G-MN patients showing complement activation of both the alternative and lectin
      pathways associated with IgG2 and IgG4.

PMID- 20151160
TI  - Childhood course of renal insufficiency in a family with a uromodulin gene
      mutation.
AB  - Mutations in the UMOD gene encoding uromodulin (Tamm-Horsfall glycoprotein)
      result in the autosomal dominant transmission of progressive renal insufficiency
      and hypo-uricosuric hyperuricemia leading to gout at an early age. The clinical
      appearance is characterized by renal insufficiency and gout occurring in the late
      teenage years, with end-stage kidney disease characteristically developing
      between 40 and 70 years of age. This report provides a long-term characterization
      of renal functional decline in three children from one family with a novel UMOD
      mutation (c.891T>G, p.C297W) who received allopurinol and a low protein diet.
      While renal functional decline is slow in individuals with UMOD mutations, it may
      appear early in life and be associated with marked hyperuricemia. Anemia was also
      noted in this family.

PMID- 20151161
TI  - Risk factors in community-acquired urinary tract infections caused by ESBL
      producing bacteria in children.
AB  - In this study, risk factors were investigated in children with community-acquired
      urinary tract infections (UTI) caused by extended-spectrum beta-lactamases (ESBL)
      producing E. coli or Klebsiella spp. One hundred and fifty-five patients were
      diagnosed with ESBL-positive UTI (case group) in the outpatient clinics of
      Hacettepe University Children's Hospital between 1 January 2004 and 31 December
      2006. A control group, 155 out of 4,105 children, was matched by age and sex
      among children with ESBL-negative UTI. A total of 310 patients' files were
      evaluated retrospectively. As regards the symptoms of UTI, no statistical
      differences were seen between the two groups. Although the most frequently
      isolated microorganism was E. coli in both groups, Klebsiella spp. was found to
      be more frequent in those diagnosed with ESBL(+) UTI (p < 0.001). Having an
      underlying disease and hospitalization, infections, and use of antibiotics within
      the last 3 months were found to be potential risk factors (p < 0.001). With
      conditional logistic regression analysis, having an underlying disease and
      hospitalization within the last 3 months were identified as independent risk
      factors for ESBL(+) UTI. In conclusion, the recognition of risk factors for UTI,
      caused by ESBL(+) bacteria in children, may aid in the identification of high
      risk cases and may enable proper management of these patients.

PMID- 20151162
TI  - Bone pain reduction in patients with metastatic breast cancer treated with
      ibandronate-results from a post-marketing surveillance study.
AB  - BACKGROUND: Pain relief is an important treatment goal for breast cancer patients
      with metastatic bone disease and treatment should be associated with a low rate
      of side effects. This interim analysis of a prospective non-interventional study
      documents the efficacy and safety of the amino-bisphosphonate ibandronate in the
      treatment of metastatic bone disease under real-life conditions. PATIENTS AND
      METHODS: For up to 24 weeks 913 breast cancer patients received IV infusions of 6
      mg ibandronate every 3-4 weeks or 50 mg of oral ibandronate once daily. Efficacy
      variables included pain severity, analgesic use, and skeletal-related events; the
      major safety parameter was renal function, assessed by serum creatinine levels.
      Subgroup analyses were performed according to pretreatment with bisphosphonates
      (none, ibandronate, or other bisphosphonates). RESULTS: At baseline, patients
      with ibandronate pretreatment tended to have lower mean pain scores and lower
      serum creatinine levels than those pre-treated with other bisphosphonates. Over
      the observation period, analgesic use did not increase. Among the 712 patients
      reporting pain at baseline, 70% achieved an improvement in pain severity during
      treatment with ibandronate, and there was no evidence to suggest relevant
      differences in mean pain reductions with IV or oral administration of ibandronate
      or according to prior bisphosphonate treatment. Skeletal-related events were rare
      (7%). Changes in serum creatinine levels during ibandronate treatment were small
      and both formulations of ibandronate were rated as well tolerated by physicians
      and patients. CONCLUSIONS: Data from this non-interventional study confirm the
      analgesic efficacy and safety profile of IV and oral ibandronate under real-life
      conditions.

PMID- 20151163
TI  - The experience and management of neck pain in general practice: the patients'
      perspective.
AB  - The objective of this study is to investigate the perspective and expectation of
      patients presenting with neck pain in general practice. The study design is a
      qualitative analysis of patient interviews and was conducted in a primary care
      setting in Germany. Twenty patients aged 20-78, according to theoretical sampling
      were included in the study. Patients tried to cope autonomously with the
      situation and consulted GPs only if their self-help had failed. When patients
      asked for external help, they usually focused on somatic treatment options such
      as massage, physiotherapy or injections. Most patients reported to have
      experiences with somatic therapies; however, they felt that some or all of these
      treatments were inefficient or led only to short-time improvements. Patients
      often avoided psychosocial themes when talking to doctors for fear of being
      branded as 'neurotic'. Although neck pain is difficult to manage and a burden for
      patients, they have obviously found a way of both living with their pain and a
      pragmatic approach of talking about their symptoms with their doctor. According
      to the patients' statements, the interaction between doctor and patient seems to
      be rather distant, ensuring that both sides avoid any issues that might touch
      upon psychological aspects of neck pain.

PMID- 20151164
TI  - A distinct tospovirus causing necrotic streak on Alstroemeria sp. in Colombia.
AB  - A tospovirus causing necrotic streaks on leaves was isolated from Alstroemeria
      sp. in Colombia. Infected samples reacted positively with tomato spotted wilt
      virus (TSWV) antiserum during preliminary serological tests. Further analysis
      revealed a close serological relationship to tomato chlorotic spot virus (TCSV)
      and groundnut ringspot virus (GRSV). A major part of the S-RNA segment,
      encompassing the nucleocapsid (N) protein gene, the 5' untranslated region and a
      part of the intergenic region 3' of the N gene, was cloned and sequenced. The
      deduced N protein sequence showed highest amino acid identity (82%) to that of
      TCSV, indicating that the virus represents a new tospovirus species, for which
      the name Alstroemeria necrotic streak virus (ANSV) is coined. Phylogenetic
      analysis based on the N protein sequence revealed that this Alstroemeria
      infecting tospovirus clustered with tospoviruses from the American continent.
      Frankliniella occidentalis was identified as potential vector species for ANSV.

PMID- 20151165
TI  - DNA methylation pattern in a barley reconstructed karyotype with deleted
      ribosomal gene cluster of chromosome 6H.
AB  - A reconstructed barley karyotype (T-35) was utilised to study the influence of
      chromosomal rearrangements on the DNA methylation pattern at chromosome level.
      Data obtained were also compared with the distribution of Giemsa N-bands and high
      gene density regions along the individual chromosomes that have been previously
      described. In comparison to the control karyotype (T-1586), the DNA methylation
      pattern was found to vary not only in the reconstructed chromosomes but also in
      the other chromosomes of the complement. Significant remodelling process of
      methylation pattern was found also in the residual nucleolus organiser regions
      (NOR) on chromosome 5H as a consequence of deletion comprising the whole NOR of
      chromosome 6H in T-35. Moreover, differences between corresponding segments of
      the homologues with respect to some other chromosome locations were also
      observed. Repositioning of genomic DNA methylation along the metaphase
      chromosomes following chromosomal reconstruction in barley seems to be essential
      to ensure correct chromatin organisation and function.

PMID- 20151166
TI  - Tissue-specific interplay between copper uptake and efflux in Drosophila.
AB  - The vinegar fly Drosophila melanogaster is proving to be an excellent system to
      study the in vivo regulation of the essential metal copper. The Ctr1A/B and
      DmATP7 copper transport proteins have well-established roles in Drosophila copper
      uptake and efflux, respectively. Both Ctr1A and DmATP7 are essential genes,
      whereas Ctr1B mutants are viable but die in excess or depleted copper conditions.
      Less is known about the tissue-specific requirements for these three genes and
      how they interact to maintain copper homeostasis in different cell types. Here,
      we use targeted overexpression and suppression of each gene to examine these
      questions in vivo. We find that in the epidermal cells that form the adult
      thoracic and abdominal cuticle, Ctr1A plays a major role in copper uptake,
      whereas Ctr1B plays only a minor supporting role and DmATP7, as previously shown,
      is essential for transfer of copper to the trans-Golgi network. We also find that
      the copper chaperone dSco1 appears necessary for supplying the mitochondria with
      copper in these tissues. In contrast, in the developing Drosophila eye, DmATP7
      appears to be non-essential unless copper levels in these cells are artificially
      elevated. Again, Ctr1A is the main copper uptake gene in the eye, but when
      ectopically expressed, Ctr1B has greater phenotypic effects than Ctr1A.
      Furthermore, Ctr1A and Ctr1B show a dramatic synergistic interaction, indicating
      their relationship is more complicated than a simply additive one and that they
      may in fact act cooperatively for optimal copper import.

PMID- 20151167
TI  - Molecular modeling study of isoindolines as L-type Ca(2+) channel blockers by
      docking calculations.
AB  - Two series of isoindolines 1(a-g) and 2(a-g) were found by docking calculations
      to be possible L-type Ca(2+) channel (LCC) blockers. The theoretical 3-D model of
      the outer vestibule and the selective filter of the LCC was provided by Professor
      Lipkind; this model consists of transmembrane segments S5 and S6 and P-loops
      contributed by each of four repeats (I, II, III, and IV) of Ca(v) 1.2. Therefore,
      two well-known LCC blockers, nifedipine 3 and (R)-ethosuccinimide 4 were also
      evaluated, and their binding sites on the LCC were identified and compared with
      those obtained for 1(a-g) and 2(a-g). Analysis of the results shows that the
      target compounds tested probably could be LCC blockers, since they interact with
      or near the glutamic acid residues Glu393, Glu736, Glu1145 and Glu1446 (the EEEE
      locus), which belong to the LCC selectivity region. The G values for all of the
      Ca(2+) channel ligands are between-10.78 and -3.67 (kcal mol(-1)), showing that
      LCC-1b, -1e and -1f complexes are more stable than the other compounds tested.
      Therefore, theoretically calculated dissociation constants K(d) (microM) were
      obtained for all compounds. Comparing these values reveals that compounds 1b
      (0.0244 microM), 1e (0.0176 microM) and 1f (0.0125 microM) exhibit more affinity
      for the LCC than the other compounds. This screening shows that the two series of
      isoindolines probably could act as LCC blockers.

PMID- 20151168
TI  - Neutralization assay to resolve discrepancies between positive results in new
      highly sensitive anti-Toxoplasma gondii IgG assays and negative results in
      reference tests.
AB  - High sensitivity of IgG assays is required in order to diagnose Toxoplasma
      infection in immunocompromised patients and women before and during early
      pregnancy. Positive results obtained in new highly sensitive Toxoplasma IgG
      assays have been observed in sera that gave negative results in reference assays.
      To allow the resolution of these discrepancies, we developed a neutralization
      assay using 80 microg/ml of a soluble membrane fraction of Toxoplasma in the
      automated Elecsys IgG assay. We were able to block the detection of Toxoplasma
      IgG antibodies in 283 sera with IgG titers ranging from below the limit of
      detection to >2,300 IU/ml. The mean percentage of neutralization was 88%, with a
      minimum neutralization of 77%. In summary, the neutralization assay represents a
      valuable tool to confirm the specificity of Toxoplasma IgG antibodies in the sera
      of immunocompromised patients and women before and during early pregnancy.
      Discrepancies between positive results in highly sensitive Toxoplasma IgG assays
      and negative results in reference assays can, thereby, be resolved and may allow
      a decision to be made on the management of patients.

PMID- 20151169
TI  - Shear bond strength of bonding to enamel with different laser irradiation
      distances.
AB  - The aim of this study was to investigate the shear bond strength of bonding to
      enamel following laser etching with the Er:YAG or Er,Cr:YSGG laser using
      different irradiation distances. Of 99 extracted human premolar teeth, 90 were
      divided equally into nine groups. In the control group (group A) the teeth were
      etched with 38% phosphoric acid. In the laser groups (groups B-I) the enamel
      surface of the teeth was laser-irradiated, groups B-E with the Er:YAG laser and
      groups F-I with the Er,Cr:YSGG laser at distances of 1, 2, 4 and 6 mm,
      respectively. The shear bond strengths were tested using a universal testing
      machine. The shear bond strengths associated with the Er:YAG laser at 4 and 6 mm
      and the Er,Cr:YSGG laser at 2, 4 and 6 mm were significantly less than the
      strengths obtained with the other irradiation distances (p<0.001). The Er:YAG
      laser at 1 mm and the Er,Cr:YSGG laser at 1 mm etched enamel in the same manner
      (p>0.05). This finding was confirmed by scanning electron microscopy examination.
      Irradiation distance did influence the strength of adhesion to enamel. The mean
      shear bond strengths and enamel surface etching obtained with the Er:YAG laser at
      1 and 2 mm and the Er,Cr:YSGG laser at 1 mm were comparable to that obtained with
      acid etching.

PMID- 20151170
TI  - Health care expenditures and gross domestic product: the Turkish case.
AB  - Our study examines the long-term relationship among per capita gross domestic
      product (GDP), per capita health expenditures and population growth rate in
      Turkey during the period 1984-2006, employing the Johansen multivariate co
      integration technique. Related previous studies on OECD countries have mostly
      excluded Turkey-itself an OECD country. The only study on Turkey examines the
      period 1984-1998. However, after 1998, major events and policy changes that had a
      substantial impact on income and health expenditures took place in Turkey,
      including a series of reforms to restructure the health and social security
      system. In contrast to earlier findings in the literature, we find that the
      income elasticity of total health expenditures is less than one, which indicates
      that health care is a necessity in Turkey during the period of analysis.
      According to our results, a 10% increase in per capita GDP is associated with an
      8.7% increase in total per capita health expenditures, controlling for population
      growth. We find that the income elasticity of public health expenditures is less
      than one. But, in the case of private health care expenditures, the elasticity is
      greater than one, meaning that private health care is a luxury good in Turkey.

PMID- 20151171
TI  - Association of socioeconomic profiles with cardiovascular risk factors in Iran:
      the Isfahan Healthy Heart Program.
AB  - OBJECTIVES: To determine the relationship between socioeconomic status (SES) and
      cardiovascular disease (CVD) risk factors. METHODS: A representative sample of
      adult populations living in three cities in Iran was studied. The demographic and
      subjective data were collected by questionnaires prepared and validated for this
      study; physical examination and laboratory tests were conducted under standard
      protocols. Three components of SES including education, occupation, and income
      were determined. The univariate ANOVA was used for statistical analysis. RESULTS:
      The population studied (99.3% response rate) comprised 12,514 subjects (51%
      females, mean age 38.4 +/- 14.3 years). While higher education was a protective
      factor against smoking in men OR = 0.8 (95% CI = 0.7-0.8), it increased the risk
      of smoking in women OR = 1.2 (95% CI = 1.02-1.5). The other risk factors
      increased with education especially in men. Higher income level increased the OR
      of CVD risk factors. Occupation had an inverse association with the
      aforementioned risk factors. The employed individuals had higher serum lipid
      level and body mass index than unemployed individual. CONCLUSION: In line with
      previous studies, we found an association between SES and CVD risk factors.
      Education level was the strongest associated factor.

PMID- 20151172
TI  - Why "winter" vomiting disease? Seasonality, hydrology, and Norovirus epidemiology
      in Toronto, Canada.
AB  - Norovirus is a common cause of gastroenteritis, and is thought to be the
      causative agent in 68-90% of all gastroenteritis outbreaks. The seasonality of
      disease occurrence is sufficiently stereotyped to result in this disease being
      dubbed "winter vomiting disease." The genesis of this seasonality has been
      obscure. We sought to identify environmental factors associated with Norovirus
      outbreaks in Toronto, Canada. We evaluated 253 outbreaks of gastroenteritis
      linked to Norovirus between November 2005 and March 2008. Poisson regression
      models were constructed to evaluate associations between average environmental
      exposures and case counts. A case-crossover approach was used to evaluate
      associations between acute changes in environment and outbreak risk. Case
      crossover analysis indicated an association between low Lake Ontario temperature
      (<or=4 degrees C) (hazard ratio [HR], 5.61 [95% CI, 2.81-11.12]) and high flow
      (>2.5 m(3)/s) in the Don River (HR, 3.17 [95% CI, 2.30-4.36]), 1-7 days prior to
      case occurrence. For both exposure variables, the highest hazard ratios were
      found 24-48 h prior to case onset. Regression models provided further support for
      these patterns. The association between local watershed conditions and Norovirus
      outbreak risk suggest a source-water reservoir for this pathogen. We hypothesize
      that the reservoir may be maintained through the discharge of wastewater
      containing virus particles; wintertime seasonality may be explained by enhanced
      viral persistence at low temperatures.

PMID- 20151173
TI  - Descriptive epidemiology of selected olfactory tumors.
AB  - Olfactory tumors, especially olfactory neuroblastomas (ON) and carcinomas with
      neuroendocrine differentiation (CND), are extremely rare, and little descriptive
      epidemiologic information is available. The objective of this study was to more
      fully describe selected olfactory tumors using a large population-based cancer
      incidence database. The Surveillance, Epidemiology and End Results (SEER) 9
      registries limited-use data were reviewed from 1973 to 2006 for selected nasal
      cavity (C30.0) and accessory sinus (C31.0-31.9) tumors. Frequencies, incidence
      rates, and relative survival rates were estimated using SEER*Stat, v6.5.2. The
      majority of cases were squamous cell carcinoma (SCC), while the incidence of ON
      was greater than CND. For ON, the incidence was highest in the 60-79 year age
      group, while for SCC, the incidence was highest in the 80+ year age group. For
      CND, the incidence leveled off in the oldest age groups. Survival rates were
      highest for ON (>70% alive at 5 years after diagnosis) and poorest for CND (44%
      alive at 5 years). Adjuvant radiation therapy did not improve survival over
      surgery alone in ON. In SCC, survival was worse in patients who received adjuvant
      radiation compared to patients who had surgery alone. Our analysis confirms some
      previously published information, and adds new information about the incidence
      and demographics of ON and CND. In addition, our analysis documents the lack of
      benefit of adjuvant radiation in ON. It is not feasible to conduct prospective
      trials in patients with these rare diseases, and the importance of registry data
      in learning about olfactory tumors is emphasized.

PMID- 20151174
TI  - A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood
      progressive low-grade glioma.
AB  - After successfully using cisplatin (30 mg/m(2)/day) and etoposide (150
      mg/m(2)/day) in ten three-day courses for progressive low-grade gliomas, a
      subsequent protocol reduced the daily doses of cisplatin (to 25 mg) and etoposide
      (to 100 mg), with the objective of achieving the same response and three-year PFS
      rates with lower neurotoxicity and myelotoxicity. We treated 37 patients (median
      age 6 years); 23 had optochiasmatic tumours and nine were metastatic cases.
      Diagnoses were clinical in 13 cases and histological in 24, and comprised:
      pilocytic astrocytoma (17), ganglioglioma (3), pilomyxoid astrocytoma (2), and
      fibrillary astrocytoma (2). Treatment was prompted by radiological evidence of
      progression and/or clinical deterioration a median 18 months after the first
      diagnosis. After initial MRI staging, neurological and clinical examinations were
      performed before each chemotherapy cycle, with MRI after the first three courses
      and every three months thereafter. After a median 48 months, a volume reduction
      was appreciable in 24 cases (65%) and response was maximum 12 months after
      starting treatment. The three-year EFS and OS rates were 65 and 97%,
      respectively. Clinical, neurological, or functional improvements were seen in
      26/37 cases. No children had a WBC nadir below 2,000/mm(3). Audiological toxicity
      caused damage in 4/34 cases. The previous protocol had achieved volume reductions
      in 70% of cases, causing audiological damage (data updated) in 11/31 (P = 0.023),
      with three-year PFS and OS rates of 70 and 100%, respectively. Lower doses of
      cisplatin/etoposide are still effective in progressive low-grade glioma, with
      less acute and persistent morbidity.

PMID- 20151175
TI  - Early CNS relapse in a good-risk primary mediastinal large B-cell lymphoma after
      combined chemo- and radio-therapy.

PMID- 20151176
TI  - Rebound tumour progression after the cessation of bevacizumab therapy in patients
      with recurrent high-grade glioma.
AB  - After withdrawal of bevacizumab in patients with recurrent high-grade glioma, we
      have observed a rapid tumour re-growth or "rebound" radiographic phenomenon with
      accelerated clinical decline. We retrospectively reviewed 11 patients treated at
      the Henry Ford Hermelin Brain Tumor Center with recurrent high-grade glioma who
      demonstrated a rebound progression pattern after the discontinuation of
      bevacizumab. The original tumour area-of-enhancement increased by a mean of 158%,
      when compared to the rebound magnetic resonance imaging. After rebound, no
      patients (0/8) showed a response to next-line treatments that did not include
      bevacizumab. The median survival of those re-treated with bevacizumab was 149 and
      32 days for those who received other regimens. Abrupt discontinuation of
      bevacizumab after recurrence often leads to a dramatic rebound phenomenon and
      rapid clinical decline. Slow tapering of the bevacizumab dose after tumour
      progression may prevent this from occurring and improve responsiveness to next
      line therapies.

PMID- 20151177
TI  - Zinc pyrithione induces cellular stress signaling and apoptosis in Hep-2 cervical
      tumor cells: the role of mitochondria and lysosomes.
AB  - Increased intracellular free zinc concentrations are associated with activation
      of several stress signaling pathways, specific organelle injury and final cell
      death. In the present work we examined the involvement of mitochondria and
      lysosomes and their crosstalk in free zinc-induced cell demise. We report that
      treatment of cervical tumor Hep-2 cells with zinc pyrithione leads to an early
      appearance of cytoplasmic zinc-specific foci with corresponding accumulation of
      zinc first in mitochondria and later in lysosomes. Concomitant with these
      changes, upregulation of expression of metallothionein II A gene as well as the
      increased abundance of its protein occurs. Moreover, zinc activates p53 and its
      dependent genes including Puma and Bax and they contribute to an observed loss of
      mitochondrial membrane potential and activation of apoptosis. Conversely,
      lysosomal membrane permeabilization and its promoted cleavage of Bid occurs in a
      delayed manner in treated cells and their effect on decrease of mitochondrial
      membrane potential is limited. The use of specific inhibitors as well as siRNA
      technology suggest a crucial role of MT-IIA in trafficking of free zinc into
      mitochondria or lysosomes and regulation of apoptotic or necrotic cell demise.

PMID- 20151178
TI  - Quantifying the value of markers in screening programmes.
AB  - Existing methods used to rank the value of individual screening markers in
      screening programmes are inadequate. We have developed a simple Screening Marker
      Index: (Screening Marker Index = Positive Predictive Value x Sensitivity). The
      Screening Marker Index proved to be superior to existing indices in ranking
      screening markers according to their ability to identify the conditions sought.

PMID- 20151179
TI  - Mechanism for the regulation of mammalian cGMP phosphodiesterase6. 1:
      identification of its inhibitory subunit complexes and their roles.
AB  - Cyclic GMP phosphodiesterase (PDE) in bovine rod photoreceptor outer segments
      (OS) comprises a catalytic subunit complex (Palphabeta) and two inhibitory
      subunits (Pgamma) and is regulated by the alpha subunit of transducin (Talpha).
      Here, we show an overall mechanism for PDE regulation by identifying Pgamma
      complexes in OS homogenates prepared with an isotonic buffer. Before Talpha
      activation, three Pgamma complexes exist in the soluble fraction. Complex a, a
      minor complex, contains Palphabeta, Talpha, and a protein named Pdelta. Complex
      b, Palphabetagammagamma( b ), has a PDE activity similar to that of membranous
      Palphabetagammagamma, Palphabetagammagamma( M ), and its level, although its
      large portion is Pdelta-free, is estimated to be 20-30% of the total
      Palphabetagammagamma. Complex c, (Pgamma.GDP-Talpha) (2) ( c ) , appears to be a
      dimer of Pgamma.GDP-Talpha. Upon Talpha activation, (1) complex a stays
      unchanged, (2) Palphabetagammagamma( b ) binds to membranes, (3) the level of
      (Pgamma.GDP-Talpha) (2) ( c ) is reduced as its GTP-form is produced, (4) complex
      d, Pgamma.GTP-Talpha( d ), is formed on membranes and its substantial amount is
      released to the soluble fraction, and (5) membranous Palphabetagammagamma,
      Palphabetagammagamma( M ) and/or Palphabetagammagamma( b ), becomes Pgamma
      depleted. These observations indicate that Pgamma as a complex with GTP-Talpha
      dissociates from Palphabetagammagamma on membranes and is released to the soluble
      fraction and that Pgamma-depleted PDE is the GTP-Talpha-activated PDE. After GTP
      hydrolysis, both (Pgamma.GDP-Talpha) (2) ( c ) and Pgamma.GDP-Talpha( d ),
      without liberating Pgamma, deactivate Pgamma-depleted PDE. The preferential order
      to be used for the deactivation is membranous Pgamma.GDP-Talpha( d ), solubilized
      Pgamma.GDP-Talpha( d ) and (Pgamma.GDP-Talpha) (2) ( c ) . Release of Pgamma.GTP
      Talpha complexes to the soluble fraction is relevant to light adaptation.

PMID- 20151180
TI  - Micellar nanocarriers: potential nose-to-brain delivery of zolmitriptan as novel
      migraine therapy.
AB  - PURPOSE: The investigation was aimed at developing micellar nanocarriers for nose
      to-brain delivery of zolmitriptan with the objective to investigate the pathway
      involved in the drug transport. METHODS: The micellar nanocarrier was
      successfully formulated and characterized for particle size and shape by multi
      angle dynamic light scattering, small angle neutron scattering and cryo
      transmission electron microscopy. Toxicity and biodistribution studies were
      carried out in rat. The distribution of the nasally administered labeled micellar
      nanocarrier in various regions of the rat brain was determined using the brain
      localization and autoradiography studies. RESULTS: Micellar nanocarrier of
      zolmitriptan, with size of around 23 nm, was successfully formulated. The
      spherical nature of the nanocarrier was confirmed using DLS, SANS and cryo-TEM.
      Toxicity studies indicated the safety for administration in the nasal cavity. In
      vivo biodistribution studies indicated the superiority of the developed
      nanocarrier for brain targeting when compared with the intravenous and nasal
      solutions of the drug. Brain localization and autoradiography studies illustrated
      the distribution of the drug in various regions of the brain and revealed a
      possible nose-to-brain transport pathway for the labeled drug. CONCLUSION: The
      investigation indicated the potential of the developed nanocarrier as an
      effective new-generation vehicle for brain targeting of zolmitriptan.

PMID- 20151181
TI  - Understanding the behavior of amorphous pharmaceutical systems during
      dissolution.
AB  - PURPOSE: To investigate the underlying physical processes taking place during
      dissolution of amorphous pharmaceuticals and correlate them to the observed
      solution concentration-time profiles. Felodipine and indomethacin were used as
      model hydrophobic compounds. METHODS: Concentration-time profiles were monitored
      during dissolution of the model amorphous compounds using in situ fiber-optic
      ultraviolet spectroscopy. Crystallization of the solid exposed to an aqueous
      environment was monitored using Raman spectroscopy and/or powder X-ray
      diffraction. Polarized light microscopy was used to provide qualitative
      information about crystallization processes. RESULTS: For felodipine, a small
      extent of supersaturation was generated via dissolution at 25 degrees C but not
      at 37 degrees C. The amorphous solid was found to crystallize rapidly at both
      temperatures upon exposure to the dissolution medium. Addition of low
      concentrations of polymers to the dissolution medium was found to delay
      crystallization of the amorphous solid, leading to the generation of
      supersaturated solutions. Amorphous indomethacin did not crystallize as readily
      in an aqueous environment; hence, dissolution resulted in supersaturated
      solutions. However, crystallization from these supersaturated solutions was
      rapid. Polymeric additives were able to retard crystallization from
      supersaturated solutions of both indomethacin and felodipine for up to 4 h.
      CONCLUSIONS: The dissolution advantage of amorphous solids can be negated either
      by crystallization of the amorphous solid on contact with the dissolution medium
      or through rapid crystallization of the supersaturated solution. Polymeric
      additives can potentially retard both of these crystallization routes, leading to
      the generation of supersaturated solutions that can persist for biologically
      relevant timeframes.

PMID- 20151182
TI  - Herbivore- and elicitor-induced resistance in rice to the rice water weevil
      (Lissorhoptrus oryzophilus Kuschel) in the laboratory and field.
AB  - Feeding by herbivores can change plants in ways that make them more resistant to
      subsequent herbivory. Such induced responses are better-studied in a number of
      model dicots than in rice and other cereals. In a series of greenhouse and field
      experiments, we assessed the effects of prior herbivory by the fall armyworm,
      Spodoptera frugiperda (J.E. Smith) and of exogenous applications of jasmonic acid
      (JA) on the resistance of rice plants to the rice water weevil, Lissorhoptrus
      oryzophilus (Kuschel), the major pest of rice in the United States. Prior feeding
      by S. frugiperda and treatment of plants with exogenous JA resulted in increases
      in the resistance of plants to the weevil. Increases in resistance were
      manifested as reduced numbers of eggs and first-instars associated with armyworm
      injured or JA-treated plants relative to control plants. In field experiments,
      there was a transient but significant reduction in the number of immature L.
      oryzophilus on JA-treated plants relative to untreated plants. To our knowledge,
      this is the first example of direct induced resistance in rice demonstrated in
      small-plot field experiments. We discuss the potential for the use of elicitor
      induced resistance in rice.

PMID- 20151183
TI  - Video tool to promote knowledge of syphilis among black and Hispanic men
      recruited from clinical and non-clinical settings.
AB  - Recent syphilis outbreaks in metropolitan cities are attributed to men who have
      sex with men (MSM) with a significant proportion of Black or Hispanic identity.
      However, there are few syphilis interventions that are tailored to minority MSM.
      METHODS: We conducted a randomized controlled trial to assess whether Black and
      Hispanic MSM recruited from various venues who viewed the "Syphilis and Men"
      video showed an increase in syphilis knowledge, regardless of self-reported
      characteristics associated with increased risk for syphilis infection. RESULTS:
      Of the 168 participants, 91.1% were Black or Hispanic and 64.9% had a male
      partner in the past 6 months. The video intervention group had a significant
      increase of 19.5-20.9 percentage points on the post-test survey, depending on the
      venue. This difference was present irrespective of participant socio-demographic
      and health-related characteristics. DISCUSSION: The "Syphilis and Men" video is a
      brief, cost-limited intervention to promote syphilis knowledge among Black and
      Hispanic MSM that can potentially be implemented in various venues.

PMID- 20151184
TI  - Should the DSM V drop Asperger syndrome?
AB  - The DSM IV defines Asperger syndrome (AS) as a pervasive developmental (autistic
      spectrum) disorder characterized by social deficits and rigid focused interests
      in the absence of language impairment and cognitive delay. Since its inclusion in
      the DSM-IV, there has been a dramatic increase in its recognition both in
      children and adults. However, because studies have generally failed to
      demonstrate a clear distinction between AS and autism, some researchers have
      called for its elimination from the forthcoming DSM V. This report argues for a
      modification of its diagnostic criteria and its continued retention in the
      diagnostic manual.

PMID- 20151185
TI  - The Training and Assessment of Relational Precursors and Abilities (TARPA): a
      preliminary analysis.
AB  - The TARPA (Training & Assessment of Relational Precursors & Abilities) is a
      recently developed computer-based protocol for the assessment of a progression of
      key domains of responding critical to the development of generative language. In
      the current pilot study, five children with autism were assessed using the TARPA
      and their score on this protocol was correlated with ratings on the Vineland
      Adaptive Behavior Scales. Findings showed a statistically significant
      correlation. This and other features of TARPA performance and their implications
      for future testing and development of this protocol are discussed.

PMID- 20151186
TI  - Constructs assessed by the GARS-2: factor analysis of data from the
      standardization sample.
AB  - The GARS-2 (Gilliam 2006) is widely used for autism screening; however, the
      validity of its three conceptually-derived subscales has not been evaluated. In
      this study, exploratory (EFA) and confirmatory (CFA) factor analyses of data from
      matched subgroups of the standardization sample did not support the GARS-2
      subscale structure. EFAs identified four factors in the model development
      subgroup (n = 496): stereotyped/repetitive behavior, stereotyped/idiosyncratic
      language, word use problems, and social impairment. CFAs supported this model in
      the replication subgroup (n = 494). Findings suggest that the GARS-2 subscales
      have limited clinical utility and that the Autism Index should be interpreted
      with caution. Although more research is needed, the clinical utility of the four
      empirically-derived scales may be limited by factors related to item content and
      test development procedures.

PMID- 20151187
TI  - Over-expression of the HIV-1 Rev promotes death of nondividing eukaryotic cells.
AB  - Expression of the human immunodeficiency virus type 1 (HIV-1) Rev protein is
      essential for completion of the viral life cycle. Rev mediates nuclear export of
      partially spliced and unspliced viral transcripts and therefore bears a nuclear
      localization signal (NLS) as well as a nuclear export signal (NES), which allow
      its nucleocytoplasmic shuttling. Attempts to express the wild-type Rev protein in
      eukaryotic human cultured cells have encountered difficulties and so far have
      failed. Here we show that accumulation of Rev, which occurs in nondividing Rev
      expressing cells or when such cells reach confluency, results in death of these
      cells. Cell death was also promoted by addition of a cell permeable peptide
      bearing the Rev-NES sequence, but not by the Rev-NLS peptide. Our results
      probably indicate that binding of excess amounts of the Rev protein or the NES
      peptide to the exportin receptor CRM1 results in cells' death.

PMID- 20151188
TI  - The burrowing crab Neohelice granulata as potential bioindicator of heavy metals
      in estuarine systems of the Atlantic coast of Argentina.
AB  - This paper presents the concentrations of total copper, lead, cadmium, and zinc
      in hepatopancreas of the burrowing crab Neohelice granulata from the Samborombon
      Bay (La Plata River estuary) and the Mar Chiquita coastal lagoon, Argentina. The
      highest accumulation of lead was observed in Mar Chiquita samples, whereas
      copper, zinc, and cadmium concentrations were higher in those from Samborombon
      Bay. Marked temporal and geographic availability differences were observed, while
      sexual differences only were observed for zinc. Finally, the validity of using
      this species as bioindicator of heavy-metal pollution within the assessed
      estuarine ecosystems is discussed.

PMID- 20151189
TI  - E-waste scenario in India, its management and implications.
AB  - Electronic waste or E-waste comprises of old, end-of-life electronic appliances
      such as computers, laptops, TVs, DVD players, refrigerators, freezers, mobile
      phones, MP3 players, etc., which have been disposed of by their original users. E
      waste contains many hazardous constituents that may negatively impact the
      environment and affect human health if not properly managed. Various
      organizations, bodies, and governments of many countries have adopted and/or
      developed the environmentally sound options and strategies for E-waste management
      to tackle the ever growing threat of E-waste to the environment and human health.
      This paper presents E-waste composition, categorization, Global and Indian E
      waste scenarios, prospects of recoverable, recyclable, and hazardous materials
      found in the E-waste, Best Available Practices, recycling, and recovery processes
      followed, and their environmental and occupational hazards. Based on the
      discussion, various challenges for E-waste management particularly in India are
      delineated, and needed policy interventions were discussed.

PMID- 20151190
TI  - Distribution and ecosystem risk assessment of polycyclic aromatic hydrocarbons in
      the Luan River, China.
AB  - The distribution and ecosystem risk of 16 polycyclic aromatic hydrocarbons (PAHs)
      in the Luan River, China, has been investigated. summation operatorPAHs levels
      ranged from 37.3 to 234 ng L(-1) in water, from 20.9 to 287 ng g(-1) in sediment
      and from 36.9 to 378 ng g(-1) in bank soil, respectively. A method based on toxic
      equivalency factors (TEFs) and risk quotient (RQ) which can be used to assess the
      ecosystem risk of summation operatorPAHs sensitively and accurately was invented
      and a new ecosystem risk classification of summation operatorPAHs was suggested.
      The results indicated that the PAHs in aquatic environment of the Luan River
      resulted in low ecosystem risk and at S9 the ecosystem risk of PAHs in water was
      moderate. Low and moderate molecular PAHs presented much more ecosystem risk than
      high molecular PAHs in the Luan River basin and the mean ecosystem risk in water
      was higher than that in sediment and bank soil.

PMID- 20151192
TI  - Start-up rhetoric in eight speeches of Barack Obama.
AB  - Our purpose in the following was to investigate the start-up rhetoric employed by
      U.S. President Barack Obama in his speeches. The initial 5 min from eight of his
      speeches from May to September of 2009 were selected for their variety of
      setting, audience, theme, and purpose. It was generally hypothesized that Barack
      Obama, widely recognized for the excellence of his rhetorical performance, would
      pursue both constant and variable strategies in his effort to establish contact
      with his audience. More specifically, it was hypothesized that the make-up of the
      audience--primarily native or non-native speakers of English--would be a
      prominent independent variable. A number of temporal and verbal measures were
      used as dependent variables. Variations were evident in mean length in syllables
      and duration in seconds of utterances (articulatory phrases), articulation rate
      in syllables per second of ontime, mean duration of silent pauses in seconds, and
      frequency of fillers, hesitations, colloquial words and phrases, introductory
      phrases, and 1st person singular pronominals. Results indicated that formality
      versus informality of the setting and presence or absence of a teleprompter were
      more prominent than native versus non-native audiences. Our analyses confirm
      Obama's skillfulness in challenging and variable settings and clearly detect
      orderliness and scientific generalizability in language use. The concept of
      orality/literacy provides a theoretical background and emphasizes dialogical
      interaction of audience and speaker.

PMID- 20151191
TI  - Accuracy of physician self-report of Spanish language proficiency.
AB  - As health systems strive to meet the needs of linguistically diverse patient
      populations, determining a physician's non-English language proficiency is
      becoming increasingly important. However, brief, validated measures are lacking.
      To determine if any of four self-reported measures of physician Spanish language
      proficiency are useful measures of fluency in Spanish. Physician self-report of
      Spanish proficiency was compared to Spanish-speaking patients' report of their
      physicians' language proficiency. 110 Spanish-speaking patients and their 46
      physicians in two public hospital clinics with professional interpreters
      available. Physicians rated their Spanish fluency with four items: one general
      fluency question, two clinically specific questions, and one question on
      interpreter use. Patients were asked if their doctor speaks Spanish ("yes/no").
      Concordance, sensitivity, specificity, and positive and negative predictive
      values (PPV, NPV) were calculated for each of the items, and receiver operating
      (ROC) curves were used to compare performance characteristics. Concordance
      between physician and patient reports of physician Spanish proficiency ranged
      from 84 to 91%. The PPV for each of the four items ranged from 91 to 99%, the NPV
      from 60 to 90%, and the area under their ROC curves from 90 to 95%. The general
      fluency question gave the best combination of PPV and NPV, and the item on
      holding sensitive discussions had the highest PPV, 99%. Physicians who reported
      fluency as "fair" were as likely to have patients report they did not speak
      Spanish as that they did. Physician self-report of Spanish language proficiency
      is highly correlated with patient report, except when physicians report "fair"
      general fluency. In settings where no financial or other incentives are linked to
      language skills, simple questions may be a useful way to assess physician
      language proficiency.

PMID- 20151194
TI  - The role of infrastructure in the transformation of child-adolescent mental
      health systems.
AB  - There is a widespread recognition that the mental health system is not effective
      in meeting the needs of the children, adolescents, and families who seek its
      services. In response to this recognition, researchers and policy makers are
      developing and implementing strategies to transform mental health systems. This
      paper suggests that transformational interventions should not proceed faster than
      our understanding of the complexities of a mental health system. In a complex
      system, all component parts are interactive and interdependent. Problems with one
      component cannot be solved in isolation from other components. The inter
      relationships between problems create inter-dependencies; and changes in the
      balance of these inter-dependencies can cause dramatic shifts in policy
      priorities, such as when managers of mental health systems respond to budget
      reductions in a recessionary economy. This paper examines the problem domains in
      mental health systems that are affected by complexity dynamics, and proposes that
      a well-built infrastructure is a necessary foundation for structural change in a
      child-adolescent mental health system. The concept of metastructure is proposed
      to account for the rule-based processes that govern the actions of agents within
      a system.

PMID- 20151193
TI  - Regional differences in the sensitivity of MEG for interictal spikes in epilepsy.
AB  - MEG interictal spikes as recorded in epilepsy patients are a reflection of
      intracranial interictal activity. This study investigates the relationship
      between the estimated sources of MEG spikes and the location, distribution and
      size of interictal spikes in the invasive ECoG of a group of 38 epilepsy patients
      that are monitored for pre-surgical evaluation. An amplitude/surface area measure
      is defined to quantify and rank ECoG spikes. It is found that all MEG spikes are
      associated with an ECoG spike that is among the three highest ranked in a
      patient. Among the different brain regions considered, the fronto-orbital, inter
      hemispheric, tempero-lateral and central regions stand out. In an accompanying
      simulation study it is shown that for hypothesized extended sources of larger
      sizes, as suggested by the data, source location, orientation and curvature can
      partly explain the observed sensitivity of MEG for interictal spikes.

PMID- 20151195
TI  - Mitochondrial K(ATP) channels-derived reactive oxygen species activate pro
      survival pathway in pravastatin-induced cardioprotection.
AB  - Reactive oxygen species (ROS) are important intracellular signaling molecules and
      are implicated in cardioprotective pathways including ischemic preconditioning.
      Statins have been shown to have cardioprotective effects against
      ischemia/reperfusion injury, however, the precise mechanisms remain to be
      elucidated. We hypothesized that ROS-mediated signaling cascade may be involved
      in pravastatin-induced cardioprotection. Cultured rat cardiomyocytes were exposed
      to H(2)O(2) for 30 min to induce cell injury. Pravastatin significantly
      suppressed H(2)O(2)-induced cell death evaluated by propidium iodide staining and
      the MTT assay. Incubation with pravastatin activated catalase, and prevented a
      ROS burst induced by H(2)O(2), which preserved mitochondrial membrane potential.
      Protective effects were induced very rapidly within 10 min, which was concordant
      with the up-regulation of phosphorylated ERK1/2. L-NAME, 5HD, N-acetylcysteine
      (NAC) and staurosporine inhibited ERK1/2 phosphorylation and also reduced
      pravastatin-induced cardioprotection, suggesting NO, mitochondrial K(ATP)
      (mitoK(ATP)) channels, ROS and PKC should be involved in the cardioprotective
      signaling. We also demonstrated that pravastatin moderately up-regulated ROS
      generation in a 5HD-inhibitable manner. In isolated perfused rat heart
      experiments, pravastatin administered 10 min prior to no-flow global ischemia
      significantly improved left ventricular functional recovery, and also reduced
      infarct size, which were attenuated by the treatment with NAC, 5HD, L-NAME or
      staurosporine. Administration of pravastatin from the beginning of reperfusion
      also conferred cardioprotection. Pravastatin protected the cardiomyocytes against
      oxidative stress by preventing the ROS burst and preserving mitochondrial
      function. Moderately up-regulated ROS production by mitoK(ATP) channels opening
      is involved in the pro-survival signaling cascade activated by pravastatin.

PMID- 20151196
TI  - Inhibition of mitochondrial respiration mediates apoptosis induced by the anti
      tumoral alkaloid lamellarin D.
AB  - Lamellarin D (Lam D), a marine alkaloid, exhibits a potent cytotoxicity against
      many different tumors. The pro-apoptotic function of Lam D has been attributed to
      its direct induction of mitochondrial permeability transition (MPT). This study
      was undertaken to explore the mechanisms through which Lam D promotes changes in
      mitochondrial function and as a result apoptosis. The use of eight Lam
      derivatives provides useful structure-apoptosis relationships. We demonstrate
      that Lam D and structural analogues induce apoptosis of cancer cells by acting
      directly on mitochondria inducing reduction of mitochondrial membrane potential,
      swelling and cytochrome c release. Cyclosporin A, a well-known inhibitor of MPT,
      completely prevents mitochondrial signs of apoptosis. The drug decreases calcium
      uptake by mitochondria but not by microsomes indicating that Lam D-dependent
      permeability is specific to mitochondrial membranes. In addition, upon Lam D
      exposure, a rapid decline of mitochondrial respiration and ATP synthesis occurs
      in isolated mitochondria as well as in intact cells. Evaluation of the site of
      action of Lam D on the electron-transport chain revealed that the activity of
      respiratory chain complex III is reduced by a half. To determine whether Lam D
      could induce MPT-dependent apoptosis by inhibiting mitochondrial respiration, we
      generated respiration-deficient cells (rho0) derived from human melanoma cells.
      In comparison to parental cells, rho0 cells are totally resistant to the
      induction of MPT-dependent apoptosis by Lam D. Our results indicate that
      functional mitochondria are required for Lam D-induced apoptosis. Inhibition of
      mitochondrial respiration is responsible for MPT-dependent apoptosis of cancer
      cells induced by Lam-D.

PMID- 20151197
TI  - Oligodendrocyte development and myelinogenesis are not impaired by high
      concentrations of phenylalanine or its metabolites.
AB  - Phenylketonuria (PKU) is a metabolic genetic disease characterized by deficient
      phenylalanine hydroxylase (PAH) enzymatic activity. Brain hypomyelination has
      been reported in untreated patients, but its mechanism remains unclear. We
      therefore investigated the influence of phenylalanine (Phe), phenylpyruvate (PP),
      and phenylacetate (PA) on oligodendrocytes. We first showed in a mouse model of
      PKU that the number of oligodendrocytes is not different in corpus callosum
      sections from adult mutants or from control brains. Then, using enriched
      oligodendroglial cultures, we detected no cytotoxic effect of high concentrations
      of Phe, PP, or PA. Finally, we analyzed the impact of Phe, PP, and PA on the
      myelination process in myelinating cocultures using both an in vitro index of
      myelination, based on activation of the myelin basic protein (MBP) promoter, and
      the direct quantification of myelin sheaths by both optical measurement and a
      bioinformatics method. None of these parameters was affected by the increased
      levels of Phe or its derivatives. Taken together, our data demonstrate that high
      levels of Phe, such as in PKU, are unlikely to directly induce brain
      hypomyelination, suggesting involvement of alternative mechanisms in this
      myelination defect.

PMID- 20151198
TI  - Biochemical abnormalities in a patient with thymidine phosphorylase deficiency
      with fatal outcome.
AB  - Deficiency of the cytosolic enzyme thymidine phosphorylase (TP) causes a
      multisystem disorder called mitochondrial neurogastrointestinal encephalomyopathy
      (MNGIE) syndrome. Clinical symptoms are gastrointestinal dysfunction, muscle
      involvement and neurological deterioration. TP deficiency is biochemically
      characterised by accumulation of thymidine and deoxyuridine in body fluids and
      compromised mitochondrial deoxyribose nucleic acid (mtDNA) integrity (depletion
      and multiple deletions). In this report we describe a patient with the clinical
      and biochemical features related to the end stage of the disease. Home parenteral
      nutrition had started to improve the clinical condition and preparations were
      initiated for stem cell transplantation (SCT) as a last resort treatment.
      Unfortunately, the patient died during the induction phase of SCT. This report
      shows that TP deficiency is a severe clinical condition with a broad spectrum of
      affected tissues. TP deficiency can be easily determined by the measurement of
      pyrimidine metabolites in body fluids and TP activity in peripheral blood
      leucocytes. Early detection and treatment may prevent the progress of the
      clinical symptoms and, therefore, should be considered for inclusion in newborn
      screening programmes. 

PMID- 20151199
TI  - Disease mechanisms and protein structures in fatty acid oxidation defects.
AB  - In fatty acid oxidation defects, the majority of gene variations are of the
      missense type and, therefore, prone to inducing misfolding in the resulting
      mutant protein. The fate of the mutant protein depends on the nature of the gene
      variation and other genetic factors as well as cellular and environmental
      factors. Since it has been shown that certain fatty acid oxidation enzyme
      proteins, exemplified by mutant medium-chain and short-chain acyl-CoA
      dehydrogenases as well as electron transfer flavoprotein and electron transfer
      flavoprotein dehydrogenase, may accumulate during cellular stress, e.g. elevated
      temperature, there is speculation about how such proteins may disturb the
      integrity of the putative fatty acid oxidation metabolone, in which the two
      flavoproteins link the matrix-located acyl-CoA dehydrogenases to the respiratory
      chain in the mitochondrial inner membrane. However, since studies so far have not
      been able to define the fatty acid oxidation metabolone, it is concluded that new
      concepts and refined techniques are required to answer these questions and
      thereby contribute to the elucidation of the cellular pathophysiology and the
      genotype-phenotype relationship in fatty acid oxidation defects.

PMID- 20151200
TI  - Classical galactosemia in Estonia: selective neonatal screening, incidence, and
      genotype/phenotype data of diagnosed patients.

PMID- 20151201
TI  - Long-term correction of murine phenylketonuria by viral gene transfer: liver
      versus muscle.
AB  - Current therapy for phenylketonuria (PKU) consists of life-long dietary
      restriction of phenylalanine (Phe), which presents problems of adherence for
      patients. Alternative therapies under investigation include, among others, the
      use of gene therapy to provide copies of wild-type, non-mutant, phenylalanine
      hydroxylase (PAH) enzyme. Expression of PAH in both liver (the usual metabolic
      source of this enzyme) and skeletal muscle is under investigation. Liver gene
      therapy, using a viral vector based on the adeno-associated viruses (AAVs),
      provided effective clearance of serum Phe that was sustained for 1 year in some
      mice. In order for PAH expression to be effective in skeletal muscle, the
      essential metabolic cofactor, tetrahydrobiopterin (BH(4)), must also be provided,
      either by supplementation or gene therapy. Both these approaches were effective.
      When transgenic PKU mice that constitutively expressed PAH in muscle were given
      intraperitoneal supplementation with BH(4), this produced (transient) effective
      clearance of Phe to normal levels. In addition, use of an AAV vector containing
      the genes for PAH, and for two key synthetic enzymes for BH(4), provided
      substantial and long-lasting correction (more than 1 year) of blood Phe levels
      when injected into skeletal muscle of PKU mice. These two strategies provide
      promising treatment alternatives for the management of PKU in patients.

PMID- 20151203
TI  - Diet and visually significant cataracts in galactosaemia: is regular follow up
      necessary?
AB  - INTRODUCTION: Classic galactosaemia is caused by a recessively inherited
      deficiency of the enzyme galactose 1 phosphate uridyl transferase (GALT).
      Patients with classical galactosaemia are at increased risk of developing
      cataracts. We sought to retrospectively review the incidence and severity of
      cataracts in the cohort of galactosaemia patients attending our national
      treatment centre and to assess a possible effect of dietary compliance on
      cataract formation and the benefits of regular ophthalmic follow-up. METHODS: We
      retrospectively reviewed the clinical notes of all patients currently attending
      our centre with classic galactosaemia and identified all those in whom cataracts
      had been diagnosed by an ophthalmologist. Compliance to diet was also reviewed
      and compared with a matched control group. RESULTS: Of 100 active patient charts,
      14 had cataracts diagnosed at some stage. Six of these persisted whereas eight
      regressed. Three occurred soon after birth. Age at cataract formation varied from
      soon after birth to 19 years of age. There was no significant difference in the
      cataract group between those who were compliant and those who were noncompliant
      with diet (p = 0.09). There was no difference in compliance between the cataract
      group and the control group (p = 0.16). None of the cataracts found were
      affecting vision. CONCLUSION: Cataracts affecting vision were not found in our
      cohort. A direct relationship between dietary compliance and cataract formation
      was not demonstrated. On the basis of our data, regular life-long ophthalmic exam
      of patients with classic galactosemia seems to be unnecessary. TAKE-HOME MESSAGE:
      Cataracts which develop in patients with classical Galactosaemia do not usually
      affect vision and may be unrelated to compliance to diet.

PMID- 20151202
TI  - Nutritional issues in treating phenylketonuria.
AB  - A phenylalanine (Phe)-restricted diet is the mainstay of phenylketonuria (PKU)
      treatment, and, in recent years, the nutritional management of PKU has become
      more complex in order to optimize patients' growth, development and diet
      compliance. Dietary restriction of Phe creates a diet similar to a vegan diet,
      and many of the nutritional concerns and questions applicable to vegans who wish
      to avoid animal products are also relevant to patients with PKU. Owing to their
      nutritional characteristics, breast milk and breastfeeding should be given
      greater consideration as a useful food in patients with PKU and in those with
      other inborn errors of metabolism. Further key issues for consideration include
      the quality of the available amino acid substitutes, the neurotrophic and
      neuroprotective effects of added long-chain polyunsaturated fatty acids (e.g.
      docosahexaenoic acid), micronutrient deficiencies, bone disease and antioxidant
      status. Long-term dietary guidance and monitoring of the nutritional status of
      patients with PKU should be part of a follow-up programme that continues for
      life.

PMID- 20151204
TI  - Fructose 1,6-bisphosphatase deficiency: enzyme and mutation analysis performed on
      calcitriol-stimulated monocytes with a note on long-term prognosis.
AB  - Fructose 1,6-bisphosphatase (FBPase) deficiency is an inborn error of metabolism
      in the gluconeogenetic pathway. During periods of low food intake or infections,
      a defect in FBPase can result in hypoglycemia, ketonuria and metabolic acidosis.
      We established a diagnostic system for FBPase deficiency consisting of enzyme
      activity measurement and mutation detection in calcitriol-stimulated monocytes.
      In healthy individuals, we showed that FBPase activity is present in monocytes
      but not in other leukocytes. We describe the clinical course of four individuals
      from two Swedish families with FBPase deficiency. Family 1: patient 1 died at the
      age of 6 months after a severe episode with hypoglycemia and acidosis; patients 2
      and 3 were followed for >30 years and were found to have a very favorable long
      term prognosis. Their FBPase activity from jejunum (residual activity 15-25% of
      healthy controls), mixed leukocytes (low or normal levels), and calcitriol
      stimulated monocytes (no detectable activity) was compared. Mutation analysis
      showed they were heterozygous for two genetic alterations (c.778G>A; c.881G>A),
      predicting amino acid exchanges at position p.G260R and p.G294E, originating from
      their parents. Family 2: patient 4 had no detectable levels of FBPase in
      stimulated monocytes. A mutation (c.648C>G) predicting a premature stop codon at
      position p.Y216X was found in one allele and a large deletion of about 300 kb,
      where the genes FBP2, FBP1 and a part of ONPEP are located, in the other. In
      conclusion, we present a reliable diagnostic system to verify an FBPase
      deficiency and find the genetic aberration.

PMID- 20151206
TI  - Too much of a good thing is wonderful? A conceptual analysis of excessive
      examinations and diagnostic futility in diagnostic radiology.
AB  - It has been argued extensively that diagnostic services are a general good, but
      that it is offered in excess. So what is the problem? Is not "too much of a good
      thing wonderful", to paraphrase Mae West? This article explores such a
      possibility in the field of radiological services where it is argued that more
      than 40% of the examinations are excessive. The question of whether radiological
      examinations are excessive cries for a definition of diagnostic futility.
      However, no such definition is found in the literature. As a response, this
      article addresses the issue of diagnostic futility in five steps. First, it
      investigates whether the concept of therapeutic futility can be adapted to
      diagnostics. A closer analysis of the concept of therapeutic futility reveals
      that this will not do the trick. Second, the article scrutinizes whether there
      are sources for clarifying diagnostic futility in the extensive debate on
      excessive radiological examination. Investigating the debate's terms and
      definitions reveals a disparate terminology and no clear concepts. On the
      contrary, the study uncovers that quite different and incompatible issues are at
      stake. Third, the article examines a procedural approach, which is widely used
      for settling controversies over utility by focusing on the role of the
      professionals. On scrutiny however, a procedural approach will not solve the
      problem in diagnostics. Fourth, a value analysis reveals how we have to decide on
      the negative value of excessive examinations before we can measure excess. The
      final and constructive part presents a definition of diagnostic futility drawing
      upon the lessons from the previous analytical steps. Altogether, too much
      radiological examination is not a good thing. This is simply because radiological
      examinations are not unanimously good. Excessive radiological examinations can be
      defined, but not by one simple general and value-neutral definition. We have to
      settle with contextually framed value-related definitions. Such definitions will
      state how bad "too much of a good thing" is and make it possible to assess how
      much of the bad thing there is. Hence we have to know how bad it is before we can
      tell how much of it there is in the world.

PMID- 20151207
TI  - On the (not so) constant proportional trade-off in TTO.
AB  - PURPOSE: The linear and power QALY models require that people in Time Trade-off
      (TTO) exercises sacrifice the same proportion of lifetime to obtain a health
      improvement, irrespective of the absolute amount. However, evidence on these
      constant proportional trade-offs (CPTOs) is mixed, indicating that these versions
      of the QALY model do not represent preferences. Still, it may be the case that a
      more general version of the QALY model represents preferences. This version has
      the property that people want to sacrifice the same proportion of utilities of
      lifetime for a health improvement, irrespective of the amount of this lifetime.
      METHODS: We use a new method to correct TTO scores for utility of life duration
      and test whether decision makers trade off utility of duration and quality at the
      same rate irrespective of duration. RESULTS: We find a robust violation of CPTO
      for both uncorrected and corrected TTO scores. Remarkably, we find higher values
      for longer durations, contrary to most previous studies. This represents the only
      study correcting for utility of life duration to find such a violation.
      CONCLUSIONS: It seems that the trade-off of life years is indeed not so
      constantly proportional and, therefore, that health state valuations depend on
      durations.

PMID- 20151208
TI  - Applying cognitive debriefing to pre-test patient-reported outcomes in older
      people with multiple sclerosis.
AB  - PURPOSE: The aim of this study was to reduce respondent burden and decrease data
      errors in patient-reported outcomes (PROs) intended for a postal survey measuring
      health and lifestyle factors that may affect quality of life in older people with
      multiple sclerosis (MS). METHODS: Participants (n = 18) were recruited from a
      database of outpatient visits. Using the qualitative diagnostic method, cognitive
      debriefing, participants completed five standardized questionnaires; Frenchay
      Activities Index, Barthel Index, Simple Lifestyle Indicator Questionnaire,
      EuroQoL EQ-5D and Personal Resources Questionnaire 2000. PRO item issues and
      respondent behaviors such as skipping items were recorded. Data collection was an
      iterative process whereby difficulties experienced by 2-3 subjects were used to
      modify the survey for following respondents until data saturation was reached.
      RESULTS: Most respondents had serious difficulties with at least one PRO item.
      Response errors fell into three main categories: (1) respondents did not read
      instructions and completed the item incorrectly, (2) respondents did not
      understand the question and required examples to clarify and (3) respondents felt
      that the pre-determined response options did not apply to them. PRO reformatting,
      minor modifications to item wording and addition of item examples improved
      precision and reduced respondent burden. CONCLUSION: Our findings support the
      notion that methods such as cognitive debriefing help improve precision of self
      reported measures in a special population such as ours.

PMID- 20151209
TI  - Carotid artery visualization during anterior skull base surgery: a novel protocol
      for neuronavigation.
AB  - Detailed knowledge of the vascular anatomy of the anterior skull base is critical
      to successful surgery in this area. Whereas conventional neuronavigational
      approaches combine MRI (+/- contrast) for tumor visualization and CT (+/- C) for
      bony and vascular anatomy, we describe the Canadian and Austrian experiences
      using a novel protocol integrating MR angiography (MRA) into surgical
      neuronavigation to provide superior visualization of the carotid arteries. The
      pre-operative imaging protocol employs a T1-weighted, 3D fast spoiled gradient
      echo MRI (+/- C) for soft tissue anatomy, a plain CT for bony anatomy, and a 3D
      time-of-flight MR angiography for carotid anatomy. The series are imported into
      the Medtronic StealthStation((R)) TREON((R)) Treatment Guidance System; during
      intra-operative neuronavigation, each series (MRI, CT, MRA) can be viewed
      individually, or layered and viewed as a composite image. Our protocol has
      important advantages. First, it provides detailed tissue, tumor, vascular and
      bony anatomy. Second, a contrast CT is not necessary; this is important, as
      numerous reports have highlighted the nephrotoxic nature of radiographic contrast
      material. Third, visualization of the carotid system is superior than can be
      obtained from CT angiography. We use this unique imaging protocol routinely for
      our endoscopic transsphenoidal surgeries to provide superior visualization of the
      carotid arteries during anterior skull base surgery.

PMID- 20151211
TI  - Utility of FDG PET/CT and brain MRI in melanoma patients with increased serum S
      100B level during follow-up.
AB  - BACKGROUND: The serum level of the S-100B protein is increasingly used as a tumor
      marker in melanoma patients. The aims of this study were to assess the clinical
      relevance of increased S-100B during follow up of high-risk melanoma patients and
      to determine the value of subsequent whole-body PET/CT and brain MRI. MATERIALS
      AND METHODS: A retrospective analysis was performed of all 46 melanoma patients
      with a normal history and physical examination who were found to have an elevated
      serum S-100B level (> or =0.10 microg/L) during follow-up between August 2006 and
      March 2009. Suspicious lesions on FDG PET/CT were biopsied for histological or
      cytological confirmation or were imaged further and followed if no pathology
      confirmation could be obtained. RESULTS: The positive predictive value of an
      elevated serum S-100B was 50%. PET/CT revealed hypermetabolic lesions in 27 of
      the 46 patients (59%). PET/CT was never false negative as confirmed by median
      follow-up of 1 year but was false positive in 4 patients. MRI revealed brain
      metastases in 1 patient (2%). Of the 23 patients with a true positive PET/CT
      scan, 6 (26%) received surgical treatment with curative intent; the other 17
      (74%) received palliative treatment or supportive care. The survival of patients
      with a normal PET/CT was longer than patients with a positive PET/CT (P = .002).
      CONCLUSIONS: An elevated serum S-100B during follow-up of high-risk melanoma
      patients has a modest 50% positive predictive value for recurrent disease.
      Subsequent PET/CT and MRI can identify patients with recurrent disease.

PMID- 20151210
TI  - Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn's disease.
AB  - AIM: Activation of sphingosine kinase (SK) is a key response to many inflammatory
      processes. The present studies test the hypothesis that an orally available SK
      inhibitor, ABC294640, would be effective in rodent models of Crohn's disease.
      METHODS: Trinitrobenzene sulfonic acid (TNBS) was administered rectally to mice
      and rats. Rats were treated with ABC294640 orally alone or in combination with
      olsalazine and disease progression was monitored. RESULTS: For both rodent
      species, treatment with ABC294640 attenuated disease progression. Colon samples
      from the ABC294640-treated animals had improved histology and cytokine parameters
      when compared with vehicle-treated animals. The expression of SK was similarly
      increased in TNBS-treated animals and in human colon tissue specimens from
      inflammatory bowel disease patients relative to normal, control patients.
      CONCLUSIONS: Sphingosine kinase may be a critical mediator of colonic damage
      during intestinal inflammation, and pharmacologic inhibitors of this enzyme may
      prove useful in the treatment of Crohn's disease.

PMID- 20151212
TI  - Preoperative staging with chest CT in patients with colorectal carcinoma: not as
      a routine procedure.
AB  - BACKGROUND: Preoperative staging of patients with colorectal carcinoma (CRC) has
      the potential benefit of altering treatment options when metastases are present.
      The clinical value of chest computed tomography (CT) in staging remains unclear.
      MATERIALS AND METHODS: All patients who undergo colorectal surgery in our
      hospital are prospectively registered, including patient, treatment, and
      histopathological characteristics; outcome; and follow-up. Since January 2007,
      routine preoperative staging CT of chest and abdomen for patients with CRC has
      been performed as part of our regional guidelines. In this observational cohort
      study, an analysis on outcome was done after inclusion of 200 consecutive
      patients. RESULTS: Synchronous metastases were present in 60 patients (30%).
      Staging chest CT revealed pulmonary metastases in 6 patients, with 1 false
      positive finding. In 50 patients indeterminate lesions were seen on chest CT
      (25%). These were diagnosed during follow-up as true metastases (n = 8), bronchus
      carcinoma (n = 2), benign lesions (n = 25), and remaining unknown (n = 15).
      Ultimately, synchronous pulmonary metastases were diagnosed in 13 patients (7%),
      in 6 patients confined to the lung (3%). In none of the patients the treatment
      plan for the primary tumor was changed based on the staging chest CT. CONCLUSION:
      The low incidence of pulmonary metastases and minimal consequences for the
      treatment plan limits the clinical value of routine staging chest CT before
      operation. It has several disadvantages such as costs, radiation exposure, and
      prolonged uncertainty because of the frequent finding of indeterminate lesions.
      Based on this study, a routine staging chest CT in CRC patients is not advocated.

PMID- 20151213
TI  - Extended resection: is it feasible for pulmonary metastases?
AB  - BACKGROUND: Extended resections may be necessary to achieve tumor-free borders
      for secondary pulmonary malignancies. This study was performed to analyze the
      outcomes that result from extended resections of pulmonary metastases. METHODS:
      Between February 1991 and December 2008, a total of 25 extended pulmonary
      resections (resection of the chest wall and diaphragm, vascular procedures,
      sleeve resections, pneumonectomies, atrial resections, and completion
      pneumonectomies) were performed on 250 patients undergoing 319 metastasectomy
      procedures. The extended resection group was analyzed in terms of disease-free
      interval, type of resection, operative morbidity, mortality, and survival and was
      then compared with patients who underwent lobar or sublobar resections. RESULTS:
      The extended resection group consisted of 14 male and 11 female patients. The
      mean disease-free interval was 36.02 (minimum 6, maximum 132) months. The
      extended resection rate was 10%. After 30 days, all patients were alive. For all
      extended metastasectomy groups, actuarial 5-year survival rates from the time of
      the extended metastasectomy were 16.3%. Mean survival times of patients who
      underwent extended resection and lobar or sublobar resection were 40 months (SD =
      11) (95% confidence interval, 19-61) and 20 months (SD = 3) (95% confidence
      interval, 14-26), respectively. This difference was not statistically significant
      (P = 0.09) (Fig. 2). In the subgroup analysis, survival in the extended
      resections and lobar or sublobar resections groups was not statistically
      significant (osteosarcoma, P = 0.758; epithelial tumor, P = 0.11). CONCLUSIONS:
      Extended resections, which can be performed during pulmonary metastasectomies of
      patients with tumor-free surgical borders, may establish curative benefits, with
      low rates of mortality and morbidity.

PMID- 20151214
TI  - Skin-sparing mastectomy and immediate breast reconstruction in the management of
      locally recurrent breast cancer.
AB  - AIM: To investigate whether skin-sparing mastectomy (SSM) and immediate breast
      reconstruction (IBR) is a possible treatment option in selected cases of locally
      recurrent breast cancer after previous breast-conserving therapy (BCT). MATERIAL
      AND METHODS: Sixty consecutive patients were treated by SSM and IBR between 1995
      and 2008 for ipsilateral breast tumour recurrence (IBTR). Selection criteria
      consisted of: IBTR <3 cm size, not infiltrating skin or chest wall, primarily
      node negative, recurrence >3 years after primary operation, and no metastases.
      Patient records were analysed retrospectively and follow-up data on patient
      outcome included. RESULTS: The reconstruction method consisted of 40 free
      abdominal flaps, 18 latissimus dorsi (LD) flaps with or without an implant, and
      two cases of implant only. Twenty-three patients received adjuvant oncological
      therapy. During median follow-up of 66 months, 11 patients (18%) developed
      disease relapse, including 6 (10%) local re-recurrences. CONCLUSION: IBR is a
      possible treatment option for patients who develop local recurrence following
      earlier BCT. Our local re-recurrence rate of 10% compares well with that
      following salvage mastectomy for IBTR. Of patients, 43% did not actually meet our
      selection criteria but yet appeared to fare well in terms of outcome. Therefore
      we should re-evaluate our selection criteria.

PMID- 20151215
TI  - Micrometastatic node-positive breast cancer: long-term outcomes and
      identification of high-risk subsets in a large population-based series.
AB  - PURPOSE: The prognostic implication of breast cancer with nodal micrometastases
      measuring >0.2 mm but < or =2 mm (pNmic) is unclear. This study evaluates
      survival in pNmic relative to node-negative (N0) and macroscopic node-positive
      (pNmac) disease in a large population-based series. METHODS: Subjects were 9,637
      women diagnosed between 1989 and 1999, referred to the British Columbia Cancer
      Agency with pT1-2, node-negative and node-positive, M0 breast cancer. Kaplan
      Meier breast-cancer-specific survival (BCSS) and overall survival (OS) were
      compared between patients with pN0 (n = 7,988), pNmic (n = 491), and pNmac
      disease (n = 1,158), according to the number of positive nodes and the lymph node
      ratio (LNR) of positive to excised nodes. Cox regression and recursive
      partitioning analyses were performed to identify significant factors associated
      with survival. RESULTS: Median follow-up was 8.2 years. Patients with pNmic
      disease had significantly poorer outcomes compared with pN0 cancers, with
      progressively lower BCSS and OS with increasing number of positive nodes and with
      LNR > 0.25. On multivariable analysis, histologic subtype, T stage, number of
      positive nodes, LNR, grade, lymphovascular invasion, estrogen receptor status,
      and systemic therapy use were factors significantly associated with BCSS and OS.
      Recursive partitioning trees for BCSS and OS both selected the pN/LNR variable at
      the first split, indicating that this variable provided the strongest prognostic
      separation. CONCLUSION: Patients with nodal micrometastases are a heterogeneous
      population with varying breast cancer mortality risks. The number of positive
      nodes and the LNR should be considered in conjunction with tumor factors in risk
      estimates and treatment decisions for patients with nodal micrometastatic breast
      cancer.

PMID- 20151216
TI  - Proton-beam, intensity-modulated, and/or intraoperative electron radiation
      therapy combined with aggressive anterior surgical resection for retroperitoneal
      sarcomas.
AB  - BACKGROUND: We sought to reduce local recurrence for retroperitoneal sarcomas by
      using a coordinated strategy of advanced radiation techniques and aggressive en
      bloc surgical resection. METHODS: Proton-beam radiation therapy (PBRT) and/or
      intensity-modulated radiation therapy (IMRT) were delivered to improve tumor
      target coverage and spare selected adjacent organs. Surgical resection of tumor
      and adjacent organs was performed to obtain a disease-free anterior margin.
      Intraoperative electron radiation therapy (IOERT) was delivered to any close
      posterior margin. RESULTS: Twenty patients had primary tumors and eight had
      recurrent tumors. Tumors were large (median size 9.75 cm), primarily liposarcomas
      and leiomyosarcomas (71%), and were mostly of intermediate or high grade (81%).
      PBRT and/or IMRT were delivered to all patients, preferably preoperatively (75%),
      to a median dose of 50 Gy. Surgical resection included up to five adjacent
      organs, most commonly the colon (n = 7) and kidney (n = 7). Margins were positive
      for disease, usually posteriorly, in 15 patients (54%). IOERT was delivered to
      the posterior margin in 12 patients (43%) to a median dose of 11 Gy. Surgical
      complications occurred in eight patients (28.6%), and radiation-related
      complications occurred in four patients (14%). After a median follow-up of 33
      months, only two patients (10%) with primary disease experienced local
      recurrence, while three patients (37.5%) with recurrent disease experienced local
      recurrence. CONCLUSIONS: Aggressive resection of retroperitoneal sarcomas can
      achieve a disease-negative anterior margin. PBRT and/or IMRT with IOERT may
      possibly deliver sufficient radiation dose to the posterior margin to control
      microscopic residual disease. This strategy may minimize radiation-related
      morbidity and reduce local recurrence, especially in patients with primary
      disease.

PMID- 20151217
TI  - Recurrence following laparoscopy-assisted gastrectomy for gastric cancer: a
      multicenter retrospective analysis of 1,417 patients.
AB  - BACKGROUND: The risk of recurrence and recurrence patterns after laparoscopy
      assisted gastrectomy for gastric cancer remain unclear. The objective of this
      study is to assess recurrence and its timing, patterns, and risk factors
      following laparoscopy-assisted gastrectomy from multicenter data. METHODS: A
      retrospective multicenter study was performed using data from 1,485 patients who
      had undergone laparoscopy-assisted gastrectomy for gastric cancer at ten
      institutions from 1998 to 2005. Recurrence and its timing and patterns were
      reviewed. Univariate and multivariate analyses were performed to identify risk
      factors for recurrence. RESULTS: Excluding 68 patients (9 postoperative
      mortalities, 1 synchronous distant metastasis, 2 nonadenocarcinomas, and 56
      losses to follow-up), 50 of 1,417 patients (3.5%) had recurrences. Incidence of
      recurrence was 1.6% (19/1186) in early gastric cancer and 13.4% (31/231) in
      advanced gastric cancer. Recurrence occurred in 34 of 50 patients (68.0%) within
      2 years of surgery, and in 45 of 50 patients (90.0%) within 3 years. The
      recurrence pattern was hematogenous in 17 patients (34.0%), peritoneal in 11
      (22.0%), locoregional in 10 (20.0%), distant lymph nodes in 2 (4.0%), and mixed
      in 10 (20.0%). Advanced T-classification and lymph node metastases were risk
      factors for recurrence. CONCLUSIONS: Laparoscopy-assisted gastrectomy showed
      satisfactory long-term oncologic outcomes similar to those of open surgery. The
      study provides additional evidence suggesting that laparoscopy-assisted
      gastrectomy is a good alternative to open gastrectomy in patients with gastric
      cancer of relatively early stage, although results of a randomized controlled
      trial and more long-term follow-up are needed to provide conclusive evidence.

PMID- 20151218
TI  - Development of a quantitative model of pregnane X receptor (PXR) mediated
      xenobiotic metabolizing enzyme induction.
AB  - The pregnane X receptor plays an integral role in the regulation of hepatic
      metabolism. It has been shown to regulate CYP3A4, which is the most abundant
      cytochrome P450 in the human liver. With its large and flexible ligand-binding
      domain, PXR can be activated by an enormous range of relatively small,
      hydrophobic, exogenous compounds. Upon activation, PXR partners with the retinoid
      X receptor (RXR) to form a heterodimer. The newly formed heterodimer binds to an
      appropriate DNA response element, causing increased transcription. This leads to
      an induction in the level of CYP3A4. These mechanistic steps are included into a
      biologically-based mathematical model. The quantitative model predicts fold level
      inductions of CYP3A4 mRNA and protein in response to PXR activation. Model
      parameter values have been taken from literature when appropriate. Unknown
      parameter values are estimated by optimizing the model results to published in
      vivo and in vitro data sets. A sensitivity analysis is performed to evaluate the
      model structure and identify future data needs which would be critical to
      revising the model.

PMID- 20151219
TI  - A mathematical model of HIV infection: Simulating T4, T8, macrophages, antibody,
      and virus via specific anti-HIV response in the presence of adaptation and
      tropism.
AB  - A mathematical model of the host's immune response to HIV infection is proposed.
      The model represents the dynamics of 13 subsets of T cells (HIV-specific and
      nonspecific, healthy and infected, T4 and T8 cells), infected macrophages,
      neutralizing antibodies, and virus. The results of simulation are in agreement
      with published data regarding T4 cell concentration and viral load, and exhibit
      the typical features of HIV infection, i.e. double viral peaks in the acute
      stage, sero conversion, inverted T cell ratio, establishment of set points,
      steady state, and decline into AIDS. This result is achieved by taking into
      account thymic aging, viral and infected cell stimulation of specific immune
      cells, background nonspecific antigens, infected cell proliferation, viral
      production by infected macrophages and T cells, tropism, viral, and immune
      adaptation. Starting from this paradigm, changes in the parameter values simulate
      observed differences in individual outcomes, and predict different scenarios,
      which can suggest new directions in therapy. In particular, large parameter
      changes highlight the potentially critical role of both very vigorous and
      extremely damped specific immune response, and of the elimination of virus
      release by macrophages. Finally, the time courses of virus, antibody and T cells
      production and removal are systematically investigated, and a comparison of T4
      and T8 cell dynamics in a healthy and in a HIV infected host is offered.

PMID- 20151221
TI  - The new heart failure diet: less salt restriction, more micronutrients.

PMID- 20151222
TI  - Update in medical education.

PMID- 20151224
TI  - Optimized culture conditions for the efficient production of porcine adenylate
      kinase in recombinant Escherichia coli.
AB  - Temperature shift cultivations with amino acid supplementation were optimized to
      produce porcine adenylate kinase (ADK) in recombinant Escherichia coli harboring
      a pUC-based recombinant plasmid under the control of the trp promoter. With
      regard to temperature control, the culture condition was initially maintained at
      35 degrees C for cellular growth, but ADK expression was suppressed until the
      late logarithmic growth phase; subsequently, a temperature shift was applied
      (from 35 degrees C to 42 degrees C), which resulted in maximal ADK production. In
      addition, supplementation of amino acids, especially valine and leucine, during
      the temperature shift stimulated ADK expression from 3.5% to 9.2% and 8.6% of the
      total protein, respectively. After optimization, 1 g ADK per liter was produced
      within 16 h of cultivation with a dry cell weight of 21.8 g/l. In this system,
      there was no loss of the recombinant plasmid during cultivation without selective
      pressure.

PMID- 20151220
TI  - Elevated production of docosahexaenoic acid in females: potential molecular
      mechanisms.
AB  - Observational evidence suggests that in populations consuming low levels of n-3
      highly unsaturated fatty acids, women have higher blood levels of docosahexaenoic
      acid (DHA; 22:3n-6) as compared with men. Increased conversion of alpha-linolenic
      acid (ALA; 18:3n-3) to DHA by females has been confirmed in fatty acid stable
      isotope studies. This difference in conversion appears to be associated with
      estrogen and some evidence indicates that the expression of enzymes involved in
      synthesis of DHA from ALA, including desaturases and elongases, is elevated in
      females. An estrogen-associated effect may be mediated by peroxisome proliferator
      activated receptor-alpha (PPARalpha), as activation of this nuclear receptor
      increases the expression of these enzymes. However, because estrogens are weak
      ligands for PPARalpha, estrogen-mediated increases in PPARalpha activity likely
      occur through an indirect mechanism involving membrane-bound estrogen receptors
      and estrogen-sensitive G-proteins. The protein kinases activated by these
      receptors phosphorylate and increase the activity of PPARalpha, as well as
      phospholipase A(2) and cyclooxygenase 2 that increase the intracellular
      concentration of PPARalpha ligands. This review will outline current knowledge
      regarding elevated DHA production in females, as well as highlight interactions
      between estrogen signaling and PPARalpha activity that may mediate this effect.

PMID- 20151225
TI  - A new process for wine production by penetration of yeast in uncrushed frozen
      grapes.
AB  - Different types of red and white wines were prepared by fermentation of the juice
      which was naturally separated from uncrushed frozen grapes during thawing (A) and
      from the residual juice by fermentation inside the berries (B). Yeast penetrated
      the skin of uncrushed grapes and fermented the content completely. The new types
      of wines were compared with wines prepared conventionally from the whole material
      of frozen grapes. Chemical and chromatographic analysis (gas chromatography (GC)
      and solid-phase microextraction-GC/mass spectrometry) showed similar profiles of
      the aroma volatiles but with significant quantitative differences among the new
      types of wines, which reflected to the differences observed during the sensory
      evaluations. The majority of identified compounds were esters, with higher
      amounts found in (A) wines due to the higher concentration of the must which was
      separated during thawing. The proposed process is new and of industrial interest
      for the production of different types of wines from the same raw material in one
      fermentation batch.

PMID- 20151228
TI  - Suppression of Na+/H + exchanger 1 by RNA interference or amiloride inhibits
      human hepatoma cell line SMMC-7721 cell invasion.
AB  - Na(+)/H(+) exchanger 1 (NHE1), a primary regulator of intracellular pH (pHi) and
      extracellular pH (pHe), plays a significant role in acidifying the tumor
      microenvironment, possibly resulting in their malignant potential. However,
      currently, very little is known about the roles of NHE1 in invasion of
      hepatocellular carcinoma (HCC) cells. We have recently shown that NHE1 is over
      expressed in HCC tissues and that this increased expression is associated with
      HCC invasiveness. In this study, we also found that NHE1 is over-expressed in HCC
      cell lines. Subsequently, we silenced NHE1 expression in the human HCC cell line
      SMMC-7721 using RNA interference (RNAi) and examined the invasiveness and
      proliferation of NHE1-silenced SMMC-7721 cells and the matrix metalloproteinase-2
      (MMP-2) activity. The knockdown of NHE1 expression significantly inhibited the
      invasive ability of SMMC-7721 cells but had only a minor effect on the cellular
      proliferation rate. Moreover, NHE1 knockdown significantly reduced the secretion
      of MMP-2. Further experiment using amiloride (an inhibitor of NHE1) confirmed the
      above result. Together, these findings indicate that NHE1 has an important role
      in SMMC-7721 cell invasion and that NHE1 might be a new target of HCC treatment.

PMID- 20151227
TI  - Cell-based assays for high-throughput screening.
AB  - Cell-based assays represent approximately half of all high-throughput screens
      currently performed. Here, we review in brief the history and status of high
      throughput screening (HTS), and summarize some of the challenges and benefits
      associated with the use of cell-based assays in HTS. Approaches for successful
      experimental design and execution of cell-based screens are introduced, including
      strategies for assay development, implementation of primary and secondary
      screens, and target identification. In doing so, we hope to provide a
      comprehensive review of the cell-based HTS process and an introduction to the
      methodologies and techniques used.

PMID- 20151229
TI  - Allogeneic blood transfusion in patients in Dukes B stage of colorectal cancer.
AB  - The aim of this study is to evaluate influence of allogeneic blood transfusion on
      prognosis in patients in Dukes B stage of colorectal cancer. All patients with
      colorectal cancer who were admitted at our Department of Surgery between January
      2000 and December 2004 were analyzed. One hundred fifty-one patients who
      fulfilled inclusion criteria were enrolled in further evaluation. B stage
      according to Dukes classification and curative resection were inclusion criteria.
      Exclusion criteria were polyposis syndromes, nonpolyposis syndromes, inflammatory
      bowel disease, autoimmune disease and previous blood transfusion. Patients were
      divided into two groups: Group 1 received <= 3 units of allogeneic blood
      transfusion and group 2 received >3 units of allogeneic blood transfusion.
      "Cutoff" value of 3 units of blood was defined according to our results and
      literature data. Follow-up was 5 year. There was no statistical difference
      between these groups in local recurrence (chi(2) = 0.009, P > 0.05) and distant
      metastasis (chi(2) = 0.44, P > 0.05). Also, the Kaplan-Meier survival curves were
      calculated, and long-rank test did not show a survival difference between these
      two groups (log rank = 0.075, P > 0.05). Postoperative complications are
      significantly more frequent in Group 2 (chi(2) = 4.67, P < 0.05). Multivariate
      logistic regression analysis confirmed that intraoperative blood transfusion more
      than three units had independent influence on local recurrence. Postoperative
      transfusion more than 3 units was statistically independent prognostic factor for
      metastasis and mortality. Overall transfusion less than 3 units of allogeneic
      blood does not influence the outcome of patients in Dukes B stage of colorectal
      cancer.

PMID- 20151232
TI  - Biographical sketch: Julius Wolff, 1836-1902.
AB  - This biographical sketch on Julius Wolff corresponds to a translation of the
      historic text, Zur Lehre von der Fracturenheilung, available at DOI
      10.1007/s11999-010-1240-9 ; and a translation and abridgement of the historic
      text, Ueber die Innere Architectur der Knochen und ihre Bedeutung fur die Frage
      vom Knochenwachstum, available at DOI 10.1007/s11999-010-1239-2 . (Supplemental
      materials are available with the online version of CORR.) An accompanying
      Editorial is available at DOI 10.1007/s11999-010-1238-3 .

PMID- 20151230
TI  - Hypothermia.
AB  - Hypothermia refers to a situation where there is a drop in body core temperature
      below 35 degrees C. It is a potentially fatal condition. In forensic medicine and
      pathology, cases of hypothermia often pose a special challenge to experts because
      of their complex nature, and the often absent or nonspecific nature of
      morphological findings. The scene of the incident may raise suspicions of a crime
      initially, due to phenomena such as terminal burrowing behavior and paradoxical
      undressing. An element of hypothermia often contributes to the cause of death in
      drug- and alcohol-related fatalities, in the homeless, in immersion deaths, in
      accidents and in cases of abuse or neglect, making the condition extremely
      relevant to forensic medical specialists. The aim of this review is to give an
      overview of the pathophysiological aspects of hypothermia and to illustrate
      different aspects relevant to forensic medical casework.

PMID- 20151231
TI  - Second-generation highly cross-linked X3TM polyethylene wear: a preliminary
      radiostereometric analysis study.
AB  - BACKGROUND: First-generation highly cross-linked polyethylene liners have reduced
      the incidence of wear particle-induced osteolysis. However, failed acetabular
      liners have shown evidence of surface cracking, mechanical failure, and oxidative
      damage. This has led to the development of second-generation highly cross-linked
      polyethylene, which has improved wear and mechanical properties and resistance to
      oxidation in vitro. Owing to its recent introduction, there are no publications
      describing its clinical performance. QUESTIONS/PURPOSES: We assessed early
      clinical wear of a second-generation highly cross-linked polyethylene liner and
      compared its clinical performance with the published results of hip simulator
      tests and with first-generation highly cross-linked polyethylene annealed liners.
      PATIENTS AND METHODS: Twenty-one patients were enrolled in a prospective cohort
      study. Clinical outcome and femoral head penetration were measured for 19
      patients at 6 months and 1 and 2 years postoperatively. RESULTS: The median
      proximal head penetration was 0.009 mm and 0.024 mm at 1 and 2 years,
      respectively. The median two-dimensional (2-D) head penetration was 0.083 mm and
      0.060 mm at 1 and 2 years, respectively. The median proximal wear rate between 1
      and 2 years was 0.015 mm/year. CONCLUSIONS: The wear rate calculated was similar
      to the in vitro wear rate reported for this material; however, it was less than
      the detection threshold for this technique. Although longer followup is required
      for wear to reach a clinically quantifiable level, this low level of wear is
      encouraging for the future clinical performance of this material. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 20151233
TI  - Case report: Neuropathic arthropathy of the hip as a sequela of undiagnosed
      tertiary syphilis.
AB  - BACKGROUND: Neuropathic arthropathy is characterized by rapidly progressive bone
      destruction in the setting of impaired nociceptive and proprioceptive innervation
      to the involved joint. It is seen most commonly in the foot and ankle, secondary
      to peripheral neuropathy in patients with diabetes mellitus. Other less common
      sites of involvement may include the knee, hip, shoulder, and spine, depending on
      the underlying etiology. Neuropathic arthropathy can be associated with tabes
      dorsalis, a unique manifestation of late, tertiary neurosyphilis that may arise
      in individuals with untreated syphilis many years after initial infection, and
      usually involves the knee, or less commonly, the hip. CASE REPORT: We report the
      case of a 73-year-old man with neuropathic arthropathy of the hip and tabes
      dorsalis attributable to previously undiagnosed tertiary syphilis. There was
      considerable delay in the diagnosis and unnecessary diagnostic testing owing to
      failure to consider syphilis as the cause. LITERATURE REVIEW: With the advent of
      effective antimicrobial therapy and public health campaigns, the relationship
      between untreated syphilis and neuropathic arthropathy has been primarily a
      historic point of interest. However, current epidemiologic research suggests a
      resurgence of syphilis in the United States, with an increased incidence of
      patients presenting with manifestations of tertiary syphilis from unidentified
      and untreated primary infections. Treatment options for neuropathic arthropathy
      of the hip are limited. Arthrodesis has had poor success and treatment with THA
      has had high complication rates. CONCLUSIONS: Syphilis is not merely a historic
      cause of neuropathic arthropathy. Neurosyphilis and tabes dorsalis should be
      considered in the differential diagnosis for patients presenting with rapid joint
      destruction consistent with Charcot arthropathy and no other apparent cause.

PMID- 20151234
TI  - Executive function and survival in the context of chronic illness.
AB  - BACKGROUND: Individual differences in executive function (EF) have been shown to
      predict risk factors for chronic illness. It is not currently known whether EFs
      also predict survival time following a diagnosis of a chronic illness. PURPOSE:
      The objective of this investigation was to examine the association between
      individual differences in EF and survival time among individuals suffering from
      one or more chronic illness. METHODS: A sample of 162 community-dwelling older
      adults who suffered from a chronic illness at baseline underwent thorough medical
      and neurological examinations to ensure freedom from actual or probable dementia.
      Participants completed cognitive testing and were subsequently followed for 10
      years; survival was assessed as survival time over the follow-up interval.
      RESULTS: Findings indicated that individual differences in EF predicted survival
      time, and this association held when adjustments were made for demographic
      variables (age, sex), education, and body mass index. CONCLUSION: Individual
      differences in EF may be important determinants of survival in the context of
      chronic illness.

PMID- 20151236
TI  - Gated blood-pool SPECT versus cardiac magnetic resonance imaging for the
      assessment of left ventricular volumes and ejection fraction.
AB  - BACKGROUND: We evaluated the accuracy of planar radionuclide angiography and
      different count-based and space-based electrocardiogram (ECG)-gated blood-pool
      single-photon emission computed tomography (GBPS) algorithms for assessment of
      left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and
      ejection fraction (LVEF) compared with the gold standard of cardiac magnetic
      resonance imaging (cMRI). The goal is to assess the accuracy of a recently
      developed GBPS algorithm. METHODS AND RESULTS: Subjects had planar, GBPS, and
      cMRI sequentially. Datasets were processed by QBS software (Cedar-Sinai) and by
      MHI software (Montreal Heart Institute). Space-based approaches were used to
      compute LVEDV, LVESV, and LVEF. Count-based techniques were also used to assess
      LVEF. All results were compared to cMRI. Fifty-five patients (85% male; mean age
      63 +/- 9 years) completed the study. LVEFs and their correlations to cMRI values
      were 43 +/- 12% (r = .82), 39 +/- 14% (r = .82), and 39 +/- 13% for MHI(space),
      QBS(space), and cMRI methodologies, respectively. LVEF by count-based methods
      also demonstrated good correlation to LVEF provided by cMRI (42 +/- 13%, r = .88
      for MHI(count) and 46 +/- 15%, r = .84 for QBS(count)). Strong correlations were
      obtained for LVEDV (r = .96 for MHI and r = .92 for QBS) and for LVESV (.97 for
      MHI and r = .94 for QBS). CONCLUSIONS: All Gated blood-pool SPECT algorithms had
      significant variation in estimating LVEF. Nevertheless our software provides good
      estimates of LV volumes and LVEF. Such software may, therefore, be applied to
      assess LV morphology and function.

PMID- 20151235
TI  - Direct and buffering effects of social support among gynecologic cancer
      survivors.
AB  - BACKGROUND: There are few studies of QoL among long-term gynecologic cancer
      survivors; available data suggest significant sequelae of disease and treatment.
      Research clarifying circumstances that improve difficult survivorship
      trajectories is lacking. PURPOSE: The present study examines whether social
      support moderates the relationship between physical functioning and psychological
      outcomes by testing the stress-buffering hypothesis. METHODS: Participants (N =
      260) were gynecologic cancer survivors (cervical, n = 47; endometrial, n = 133;
      ovarian, n = 69; vulvar, n = 11). Compromised physical health was conceptualized
      as multidimensional. Social support (SNI, PSS-Fa, PSS-Fr, ISEL) was tested as a
      buffer of adverse psychological outcomes (IES-R, CES-D). RESULTS: Results for
      traumatic stress provided evidence for buffering; whereas social support was of
      general benefit for depressive symptoms. Effects varied by source and type of
      support. CONCLUSIONS: These results suggest that circumstances for gynecologic
      cancer survivors burdened with physical symptoms may be worse for those with
      fewer support resources, providing needed insight into a common target of
      psychosocial interventions for cancer survivors.

PMID- 20151237
TI  - Very late drug-eluting stent thrombosis post-exercise myocardial perfusion SPECT.

PMID- 20151238
TI  - Enhanced definition PET for cardiac imaging.
AB  - BACKGROUND: We aimed to determine in phantom and cardiac clinical studies the
      impact of a new high-resolution PET image reconstruction. METHODS: A phantom with
      cardiac insert filled with (18)F, 14 (18)F-FDG viability studies and 15 (82)Rb
      perfusion studies were acquired on a Siemens Biograph-64 (4-ring). The data were
      reconstructed with 2D- and 3D-attenuation weighted ordered subsets expectation
      maximization (AWOSEM), and high-definition reconstruction (HD.PET). We calculated
      wall/cavity contrast, contrast-to-noise ratio (CNR), wall thickness,
      motion/thickening and ejection fraction. RESULTS: In the phantom study, we found
      an increase in defect size (up to 26%), contrast (up to 48%) and CNR (1.9) with
      HD.PET as compared to standard techniques. The contrast increased on HD.PET
      images compared to 2D- and 3D-AWOSEM for viability (14.0% +/- 4.8%) and perfusion
      studies (7.3% +/- 4.3%) (P < .05). Average CNR increased with HD.PET by 79.4% +/-
      17.1% and 68.8% +/- 3.0% in viability and perfusion studies respectively (all P <
      .05). Average wall thickness with HD.PET decreased in the phantom study by 1.3 +/
      0.3 mm and the viability studies by 1.9 +/- 0.7 mm but not in the perfusion
      studies. The functional measurements were not significantly different for any
      techniques. CONCLUSIONS: We demonstrated both in phantom and patient cardiac
      studies that HD.PET improves image contrast, defect definition, and CNR.

PMID- 20151239
TI  - Evaluation of coronary artery aneurysm and stenosis using open-source myocardial
      perfusion SPECT and coronary computed tomographic angiography image fusion
      software.

PMID- 20151240
TI  - Diagnostic and prognostic value of myocardial perfusion gated SPECT in orthotopic
      heart transplant recipients.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) limits long-term survival after
      heart transplantation. Diagnostic and prognostic value of gated single photon
      emission computed tomography (gated SPECT) has not been documented in this
      setting. METHODS AND RESULTS: We identified 110 consecutive heart transplant
      recipients (with transplantation >18 months) who underwent stress-rest gated
      SPECT and coronary angiography within 1 month, and were clinically monitored in a
      single heart transplantation center. Visual scoring of perfusion and wall motion
      images used a 16-segment model. Left ventricular function was automatically
      calculated. Coronary angiography was normal in 64 patients (58%) and abnormal in
      46 (any CAV, 42%), of whom 19 had severe stenoses. Sensitivity and negative
      predictive (NPV) value were .63 and .75 for identification of any CAV, and .84
      and .96 for severe CAV. Cox regression analysis showed that independent
      predictors of cardiac death and retransplantation were the presence of any
      angiographic CAV lesions (RR = 8.816, P = .043) and a stress perfusion defect >3
      segments (RR = 5.607, P = .0053). A stress perfusion defect >3 segments predicted
      the need for late coronary revascularization >2 months (RR = 6.11, P = .0002).
      CONCLUSIONS: We conclude that perfusion gated SPECT is a useful noninvasive
      screening test and may be proposed to help identify heart transplant recipients
      with a high risk of poor clinical outcome. A normal gated SPECT was associated
      with a low risk of cardiac hard event and might alleviate the need for coronary
      angiography.

PMID- 20151241
TI  - Adolescent maturation of cortical dopamine.
AB  - Dopamine is a critical modulator of prefrontal cortical function, and it is known
      to be dysfunctional in schizophrenia. Current hypotheses on schizophrenia
      highlight developmental aspects and genetic predisposition for the disease; yet,
      symptom onset typically occurs during adolescence. Several aspects of prefrontal
      cortical circuits and their modulation by dopamine mature postnatally, as late as
      during adolescence. Here we review studies assessing the postnatal trajectory of
      dopamine control of GABA interneurons, a neuronal population that has been long
      suspected to be critical for schizophrenia pathophysiology. Dopamine modulation
      of fast-spiking interneurons changes dramatically during adolescence (postnatal
      day 45-50 in rats) with D2 agonists switching from being mildly inhibitory in
      prepubertal rats to strongly excitatory in young adult rats. In vivo recordings
      in adult rats reveal that deep-layer pyramidal neurons respond to endogenous DA
      release with suppression of firing while interneurons are activated. In adult
      rats with a neonatal ventral hippocampal lesion (NVHL), an extensively studied
      developmental model of schizophrenia, the maturation in the D2 modulation of
      interneuron physiology fails to occur, rendering a disinhibited prefrontal
      cortex. Abnormal interneuron maturation may therefore impair cognitive function
      in the adult animal.

PMID- 20151243
TI  - Persistence of long-term memory storage: new insights into its molecular
      signatures in the hippocampus and related structures.
AB  - Although much is known about long-term memory (LTM) consolidation, what puts the
      "long" in LTM is the exclusive feature of persisting over time. However, until
      recently the molecular mechanisms underneath memory persistence had never been
      properly studied. In rats, the protein translation inhibitor anisomycin impaired
      memory persistence when injected into the dorsal hippocampus 12 h after
      inhibitory avoidance (IA) training without affecting memory formation. Here, we
      also show learning-induced changes in hippocampal c-Fos, Homer 1a, Akt,
      CamKIIalpha, and ERK2 levels around 18-24 h after IA training. Thus, memory
      persistence is associated with a late phase of plasticity-related protein
      synthesis in the hippocampus.

PMID- 20151244
TI  - Colon cancer information preferences of English-as-a-second-language immigrant
      women: does language of interview matter?
AB  - Language of interview, an acculturation proxy measure, may differentiate between
      cancer information preferences of English-as-a-second-language (ESL) immigrant
      women in Canada. Using directed content analysis, we compared 28 interviews
      conducted in Spanish or English. Demographic comparisons were completed using
      paired t tests and McNemar related samples. Themes identified were: (1) using
      English language information and (2) improving information for ESL speakers. No
      differences were found in women's conversations about colon cancer by age,
      income, education, or employment. However, English interviewees resided in Canada
      longer and watched less television. Language skill and contextual factors
      influence women's confidence using English cancer information.

PMID- 20151242
TI  - Cortical and sub-cortical effects in primate models of cocaine use: implications
      for addiction and the increased risk of psychiatric illness.
AB  - Drug abuse is a serious risk factor for the incidence and severity of multiple
      psychiatric illnesses. Understanding the neurobiological consequences of repeated
      exposure to abused drugs can help to inform how those risks are manifested in
      terms of specific neurochemical mechanisms and brain networks. This review
      examines selective studies in non-human primates that employed a cocaine self
      administration model. Neurochemical consequences of chronic exposure appear to
      differ from observations in rodent studies. Whereas chronic intermittent exposure
      in the rodent is usually associated with a dose-dependent increase in
      dopaminergic response to a cocaine challenge, in the rhesus monkey, high
      cumulative exposure was not observed to cause a sensitized dopamine response.
      These non-human primate observations are concordant with clinical findings in
      human users. The results of cue exposure studies on dopaminergic transmission are
      also reviewed. Direct microdialysis measurements indicate that there is not a
      sustained increase in dopamine associated with cocaine-linked cues. As an
      alternative to striatal dopaminergic mechanisms mediating cue effects, single
      unit studies in prefrontal cortex during self-administration in monkeys suggests
      the orbitofrontal and anterior cingulate cortex are strongly engaged by cocaine
      cues. Based on the strong clinical imaging literature on cortical and cognitive
      dysfunction associated with addiction, it is proposed that the strong engagement
      of cortical systems during repeated cocaine reinforcement results in maladaptive
      changes that contribute to the risks of drug use for exacerbation of other
      psychiatric disorders.

PMID- 20151245
TI  - Current concepts of carpal tunnel syndrome: pathophysiology, treatment, and
      evaluation.
AB  - The current concepts of carpal tunnel syndrome (CTS) with respect to its
      pathophysiology, treatment, and evaluation are discussed. With regard to the
      pathophysiology of idiopathic CTS, biomechanical studies to determine the
      kinematics of the flexor tendon, and the median nerve inside the carpal tunnel
      may provide valuable insights. Different degrees of excursion between the flexor
      tendons and the median nerve could cause strain and microdamage to the synovial
      tissue; this has been microscopically observed. A biomechanical approach for
      elucidating the events that trigger the development of CTS seems interesting;
      however, there are limitations to its applications. Endoscopic carpal tunnel
      release (ECTR) is a useful technique for achieving median nerve decompression.
      However, it is not considered superior to conventional open carpal tunnel release
      in terms of fast recovery of hand function. Unless the effect of inserting a
      cannula into the diseased carpal tunnel on the median nerve function is
      quantitatively elucidated, ECTR will not be regarded as a standard procedure for
      relieving the median nerve from chronic compression. The treatment of CTS should
      be evaluated on the basis of patient-oriented questionnaires as well as
      conventional instruments because these questionnaires have been validated and
      found to be highly responsive to the treatment. It should be noted that nerve
      conduction studies exclusively evaluate the function of the median nerve, whereas
      patient-oriented questionnaires take into account not only the symptoms of CTS
      but other accompanying pathologies as well, such as flexor tenosynovitis. In
      Japan, the number of CTS patients is expected to rise; this may be attributed to
      a general increase in the life-span of the Japanese and increase in the number of
      diabetic patients. Thus, more efforts should be directed toward elucidating the
      pathophysiology of so-called idiopathic CTS, so that new treatment strategies can
      be established for CTS of different pathologies.

PMID- 20151246
TI  - Analysis of interobserver reliability for radiographic staging of coxarthrosis
      and indexes of acetabular dysplasia: a preliminary study.
AB  - BACKGROUND: We are planning a multicenter survey on coxarthrosis and acetabular
      dysplasia in Japan. To collect reliable data, we performed a preliminary study to
      elucidate the observer agreement on assessment items. METHODS: We collected
      radiographs of hip joints in eight patients with various findings of
      coxarthrosis. Twelve registered orthopedic specialists evaluated them regarding
      the roentgenographic stage of coxarthrosis and five indexes of acetabular
      dysplasia (acetabular angle, center-edge angle, acetabular roof obliquity,
      acetabular head quotient, approximate acetabular quotient). To assess observer
      agreement, we calculated the value of the kappa statistic for stages and the
      coefficient of variation for the indexes. The same 12 specialists then assessed
      the coxarthritis stage on the same radiographs 1 month after the first evaluation
      based on our own descriptions of the roentgenographic stages. RESULTS: For the
      first evaluation of the roentgenographic stage, the value of the kappa statistic
      was 0.448; and for the second evaluation it was 0.600. The results of the
      coefficient of variation for the indexes of acetabular dysplasia, ranked in
      ascending order, were as follows: acetabular angle, acetabular head quotient,
      acetabular roof obliquity, center-edge angle, approximate acetabular quotient.
      CONCLUSIONS: For the upcoming multicenter survey, clear descriptions of the
      stages of coxarthrosis and selection of appropriate indexes can be helpful for
      collecting dependable results.

PMID- 20151247
TI  - Results and prognostic factors of valgus osteotomy in middle-aged patients with
      advanced or terminal osteoarthritis of the hip.
AB  - BACKGROUND: From 1979 to 2005, a total of 279 hips in 249 patients with advanced
      and/or terminal-stage osteoarthritis of the hip underwent valgus osteotomy. Among
      them, we reviewed 256 hips in 229 patients (91.8%) with a minimum follow-up of 1
      year. We reviewed the clinical and radiological results and analyzed prognostic
      factors that may have affected the postoperative outcome. METHODS: Clinical
      evaluation was made according to the Japanese Orthopaedic Association Hip score
      (JOA score). Radiological evaluation was made according to the criteria of
      Itoman. The Kaplan-Meier method was used to calculate the probability of survival
      of valgus osteotomy from the time of the operation until the endpoint of a
      subsequent operation. To examine prognostic factors, clinical parameters and
      radiographic measurements were compared between patients in an improved group and
      an aggravated group. Additionally, clinical parameters and radiographic
      measurements were used to evaluate the JOA score at the latest follow-up.
      RESULTS: The mean JOA score was 52.6 before the operation; it was 80.6, showing
      the most marked improvement, 5 years after the operation, gradually decreased
      thereafter; and it was 65.0 after 20 years. Radiological results were good or
      fair in 78% even 10 years after the operation. The survival rates were 91%, 63%,
      and 52%, respectively, at 10, 15, and 20 years after valgus osteotomy. Concerning
      prognostic factors, the improved group tended to show preoperative good range of
      motion and unilateral involvement. Concerning the association between prognostic
      factors and the JOA score at the latest follow-up observation, the JOA score was
      significantly lower for an acetabular head index (AHI) <60% than for AHI >or=60%.
      CONCLUSIONS: Valgus osteotomy is effective joint-preserving surgery for advanced
      or terminal-stage osteoarthritis of the hip in middle-aged patients, and it is
      acceptable for clinical and radiological evaluation. If the AHI is <60%, valgus
      osteotomy should be combined with Chiari's pelvic osteotomy.

PMID- 20151248
TI  - Factors determining the 1-year survival after operated hip fracture: a hospital
      based analysis.
AB  - BACKGROUND: Factors associated with 1-year survival of hip fracture in Chinese
      ethnicities has not been clearly elucidated. The purpose of this study was to
      determine the 1-year survival associated with operated hip fracture and its
      prognostic factors in a district teaching hospital from January 1, 1998 to 2006.
      METHODS: Hip fracture admissions (ICD-9: 820) identified from an inpatient
      electronic database over a 9-year period were linked to Taiwan's national death
      registry. Actuarial analysis was used to determine the 1-year survival rates
      after hip fracture, which were further compared according to different concurrent
      illnesses. We used the Cox proportional hazard regression model to explore the
      significant determinants of 1-year survival of the study patients. RESULTS: The
      overall 1-year survival rate of all patients was 86%. This was lower if the
      operation was accompanied by certain co-morbidities, including heart failure
      [hazard ratio (HR) 6.12; 95% confidence interval (CI) 1.54-24.36], chronic
      obstructive pulmonary disease (HR 2.40; 95% CI 1.14-5.05), and pneumonia (HR
      4.26; 95% CI 1.95-9.31). In addition, elderly patients (>84 years of age) (HR
      7.34; 95% CI 2.49-21.58), arthroplasty (HR 3.69; 95% CI 1.10-12.43), operative
      delay >48 h (HR 2.86; 95% CI 1.08-7.54), low preoperative hemoglobin level (<11
      g/dl) (HR 2.58; 95% CI 1.33-5.01), and high creatinine level (>or=2 mg/dl) (HR
      2.52; 95% CI 1.07-5.95) were all significantly associated with increased
      mortality. CONCLUSIONS: The 1-year survival for patients in this study hospital,
      86%, was comparable to or higher than that of previous studies. Improved survival
      rates among hip fracture patients may be achieved by early recognition and prompt
      treatment of associated medical illnesses.

PMID- 20151249
TI  - Use of a unipedal standing test to assess the ambulation reacquisition time
      during the early postoperative stage after hip fracture in elderly Japanese:
      prospective study.
AB  - BACKGROUND: The aim of this study was to predict the ambulation reacquisition
      time after hip fracture in elderly people using the unipedal standing test during
      the early postoperative stage. METHODS: Patients with an intertrochanteric
      fracture treated with internal fixation (n = 35) and patients with a femoral neck
      fracture treated with hemiarthroplasty (n = 22) were included. A unipedal
      standing test using the nonoperated leg was performed on days 3 and 7 after the
      operation. RESULTS: Among the patients with an intertrochanteric fracture, those
      with a positive result on the unipedal standing test on postoperative day (POD) 3
      attained gait with parallel guide bars (BG) and walker-assisted gait (WG)
      significantly earlier than did patients with a negative result on the unipedal
      standing test. Patients with a positive result on the unipedal standing test on
      POD 7 attained BG, WG, and cane-assisted gait (CG) significantly earlier than did
      patients with a negative test. Among patients with a femoral neck fracture, those
      with a positive unipedal standing test result on POD 3 attained BG, WG, and CG
      significantly earlier than did patients with a negative test. Those with a
      positive test result on POD 7 attained BG, WG, and CG significantly earlier than
      did patients with a negative test. CONCLUSIONS: The unipedal standing test given
      during the early postoperative stage is a good test for predicting the ambulation
      reacquisition time. Moreover, it gives information that can help determine the
      need for subacute rehabilitation and about discharge planning and health service
      provision.

PMID- 20151250
TI  - Creation of a reflecting formula to determine a patient's indication for
      undergoing total knee arthroplasty.
AB  - BACKGROUND: The aim of this study was to develop, from patients' characteristics
      and radiography, a formula reflecting the decision for total knee arthroplasty
      (TKA) in patients with a painful osteoarthritic knee. METHODS: We reviewed
      medical records of 193 consecutive patients who had knee osteoarthritis and
      underwent primary TKA surgery and 133 consecutive patients with knee
      osteoarthritis who did not have surgery in one institution during the preceding 5
      years. Two skeletal radiologists graded, from 0 to 3, radiographic joint space
      narrowing (JSN), osteophytes, subchondral sclerosis, and subchondral cysts. The
      association between the variables and outcome were calculated by the chi-squared
      test and multivariable logistic regression. RESULTS: Women had more TKAs than men
      (P = 0.002), and the TKA and non-TKA groups differed in terms of self-care
      ability (P < 0.001). There were no significant differences in age or body mass
      index between the two groups. The relevant factors in the reflective formula were
      age, sex, self-care ability, JSN, and osteophytes in the medial compartment. The
      retrospective sensitivity and specificity for patients who underwent TKA surgery
      were 84% and 83%, respectively. The diagnostic efficacy in retrospect evaluated
      by a receiver operating characteristic curve was 0.92. CONCLUSIONS: A formula
      reflecting the decision for TKA surgery in patients with a painful osteoarthritic
      knee has been developed with acceptable diagnostic efficacy obtained
      retrospectively. The formula should be validated by further study.

PMID- 20151251
TI  - Clinical and biochemical characteristics after intra-articular injection for the
      treatment of osteoarthritis of the knee: prospective randomized study of sodium
      hyaluronate and corticosteroid.
AB  - BACKGROUND: Intra-articular injections of sodium hyaluronate (Na-HA) and
      corticosteroid (CS) are often used for the treatment of osteoarthritis (OA), and
      the clinical usefulness of such treatment has been reported. Some studies have
      discussed the effectiveness of intra-articular drug injection therapy in terms of
      the clinical results, but no cohort studies have performed evaluations of
      effectiveness based on changes in joint biomarkers. This prospective randomized
      study compared the efficacy of Na-HA and CS injections based on clinical scores
      and levels of biochemical markers for osteoarthritis. METHODS: A total of 51
      patients with knee osteoarthritis received intra-articular injections of either
      Na-HA or CS and were followed for 6 months after treatment. Pain and inflammatory
      scores were evaluated at the baseline, at 5 weeks, and at 6 months. We also
      measured joint fluid levels of hyaluronan (HA), chondroitin 6-sulfate,
      chondroitin 4-sulfate, matrix metalloproteinase (MMP)-9, and tissue inhibitor of
      MMP (TIMP)-1 at the baseline and at 5 weeks. RESULTS: In both groups, injection
      therapy significantly improved pain/inflammation scores and visual analog scale
      scores with time (P < 0.01). HA levels were significantly increased after
      injection only in the Na-HA group (P < 0.05); and the MMP-9 level decreased
      significantly after injection only in the Na-HA group (P < 0.01). Other marker
      levels did not differ significantly between groups. CONCLUSIONS: The results of
      this prospective randomized study suggest that the clinical effects of Na-HA and
      CS as local therapies for OA are comparable and that both drugs are useful.
      Considering the results of the measurement of biomarkers, compared with CS
      injection therapy Na-HA injection therapy may have protective effects on the
      articular cartilage by increasing the HA concentration in synovial fluid, as well
      as inhibitory effects on the catabolism of articular cartilage by reducing the
      MMP-9 concentration.

PMID- 20151252
TI  - Rheumatoid arthritis: a risk factor for deep venous thrombosis after total knee
      arthroplasty? Comparative study with osteoarthritis.
AB  - BACKGROUND: Recent advances in the understanding of blood coagulation processes
      favor an inflammatory basis for thrombotic events. In this study, thrombotic risk
      after total knee arthroplasty (TKA) was assessed and compared between patients
      with rheumatoid arthritis (RA) and those with osteoarthritis (OA). METHODS:
      Subjects comprised 199 patients (238 knees) with RA and 156 patients (169 knees)
      with OA. Serum D-dimer levels were measured before and after the operation.
      Lowdose unfractionated heparin was given for 7 days when patients had a history
      of previous venous thromboembolism or had a D-dimer level or >or=10 microg/ml of
      D-dimer on postoperative day 1. Doppler ultrasonography (DUS) was routinely
      performed preoperatively and on postoperative day (POD) 7 for diagnosing a deep
      venous thrombosis (DVT). RESULTS: D-dimer levels on PODs 0, 1, and 7 were,
      respectively, 4.6, 37.2, and 11.2 microg/ml for RA and 1.8, 42.3, and 13.6
      microg/ml for OA. The incidence of DUS-confirmed DVT was 20.6% in the RA group
      and 43.2% in the OA group, indicating a much higher incidence of postoperative
      DVT in OA patients (P < 0.001). Interestingly, when patients taking nonsteroidal
      antiinflammatory drugs (NSAIDs) or those >65 years of age were excluded, the
      incidence of DVT was comparable in the RA and OA groups. Symptomatic pulmonary
      embolism and DVT occurred in two and one OA patients and in one and two RA
      patients, respectively, with one postdischarge DVT included in each group.
      CONCLUSIONS: The present study revealed that the incidence of DVT following TKA
      was significantly lower in RA patients than in those with OA. However, when the
      patients were matched for age and NSAID use, the incidence of DVT was equivalent
      in the two groups. These findings may allow us to reconsider a prophylactic
      regimen for venous thromboembolism in patients with RA.

PMID- 20151253
TI  - Three-dimensional lower extremity alignment in the weight-bearing standing
      position in healthy elderly subjects.
AB  - BACKGROUND: Although assessment of lower extremity alignment is important for the
      treatment and evaluation of diseases that present with malalignment of the lower
      extremity, it has generally been performed using only plain radiographs seen in
      two dimensions (2D). In addition, there is no consensus regarding the criteria
      for quantitative three-dimensional (3D) evaluation of the relative angle between
      the femur and tibia. The purpose of this study was to establish assessment
      methods and criteria for quantitatively evaluating lower extremity alignment in
      3D and to obtain reference data from normal elderly subjects. METHODS: The normal
      alignment of 82 limbs of 45 healthy elderly subjects (24 women, 21 men; mean age
      65 years, range 60-81 years) was analyzed in 3D with regard to flexion, adduction
      abduction, and rotational angle of the knee in the weight-bearing, standing
      position. The obtained computed tomography (CT) and biplanar computed radiography
      (CR) data were used to define several anatomical axes of the femur and tibia as
      references. RESULTS: In the sagittal plane, the mean extension-flexion angle was
      significantly more recurvatum in women than in men. In the coronal plane, the
      mean 3D hip-knee-ankle angle was more varus by several degrees in this Japanese
      series than that in a Caucasian series reported previously. Regarding rotational
      alignment, the mean angle between the anteroposterior axis of the tibia and the
      transepicondylar axis of the femur in this series was slightly larger (externally
      rotated) than that of previously reported Japanese series examined in the supine
      position. CONCLUSIONS: These data are believed to represent important references
      for 3D evaluation of morbid lower extremity alignment in the weight-bearing,
      standing position and are important for biomechanical research (e.g., 3D analyses
      of knee kinematics) because the relative angles between the femur and tibia are
      assessed three-dimensionally.

PMID- 20151254
TI  - Anterior decompression and fusion versus laminoplasty for cervical myelopathy
      caused by soft disc herniation: a prospective multicenter study.
AB  - BACKGROUND: Anterior decompression and fusion (ADF) has conventionally been used,
      with stable outcomes, for cervical myelopathy caused by soft disc herniation.
      However, complications related to bone grafting and recurrence of myelopathy due
      to adjacent segment degeneration are its drawbacks. The efficacy of laminoplasty
      as an alternative has been sporadically reported, but no prospective study has
      been conducted to verify it. The purpose of this study was to determine whether
      laminoplasty is comparable for this condition. METHODS: Patients with cervical
      myelopathy caused by soft disc herniation whose preoperative disease period was
      less than 1 year were studied. The first 30 patients and the next 30 patients
      were treated by ADF and laminoplasty, respectively. All patients were given the
      same postoperative management. The outcomes were compared between the ADF and the
      laminoplasty groups consisting of 25 patients each who completed a follow-up
      examination 1 year after surgery. RESULTS: The two groups were found
      statistically matched regarding age at surgery, sex, disc level of herniation,
      anteroposterior diameter of the spinal canal, preoperative severity of
      myelopathy, cervical lordosis angle, and cervical range of motion (ROM). There
      was no statistically significant difference in the postoperative severity or
      recovery rate of myelopathy between the two groups. The amount of blood loss
      during surgery was significantly less in the laminoplasty group. Donor site pain
      and neck pain was minimal in all patients. Cervical lordosis angle and ROM were
      diminished postoperatively without a significant difference between the two
      groups. CONCLUSIONS: There was no critical difference between the ADF and
      laminoplasty groups with regard to neurological recovery and other surgery
      related factors 1 year after surgery. Laminoplasty can be employed for cervical
      myelopathy caused by soft disc herniation in particular combined with multilevel
      spinal canal stenosis to avoid secondary myelopathy.

PMID- 20151255
TI  - Nationwide survey of current medical practices for hospitalized elderly with
      spine fractures in Japan.
AB  - BACKGROUND: The status of hip fracture incidence and treatment is well known
      through nationwide surveys in Japan. However, there have been no similar studies
      on spine fractures. Therefore, we investigated current medical practices for
      them. METHODS: Altogether, 1200 hospitals were randomly selected for the survey
      with consideration of region and hospital characteristics. Questionnaire items
      included the number of hospitalized spine patients, imaging test implementation,
      type of conservative treatment, use of open surgery and vertebroplasty, and the
      number of these procedures performed in 2005. RESULTS: Responses were received
      from 473 hospitals. On the day of response, there were 14 372 hospitalized
      orthopedic patients (average 32.8/hospital). Among them were 1403 spine fracture
      patients (3.1/hospital), accounting for 13.5% of orthopedic patients. Of them,
      91.9% received conservative treatment. The mean percentage of spine fracture
      patients who were hospitalized was 39.5%. The most reliable imaging test was said
      to be magnetic resonance imaging. Casting or bracing was used in most of the
      institutions. The most common analgesic treatment was oral nonsteroidal
      antiinflammatory drugs. Open surgery and vertebroplasty were conducted for spine
      fractures in the elderly at 26.5% and 16.3% of hospitals, respectively. In these
      hospitals, 624 and 257 patients underwent open surgery and vertebroplasty,
      respectively, in 2005. CONCLUSIONS: In Japan, more than 90% of elderly patients
      hospitalized with spine fractures received conservative treatment. Surgical
      treatment, either open surgery or vertebroplasty, was performed at 30% of the
      hospitals. This study provides basic data that will contribute to planning
      improvements in spinal fracture treatment in the elderly.

PMID- 20151256
TI  - Evaluation of low back pain using the Japanese Orthopaedic Association Back Pain
      Evaluation Questionnaire for lumbar spinal disease in a multicenter study:
      differences in scores based on age, sex, and type of disease.
AB  - BACKGROUND: The Japanese Orthopaedic Association (JOA) has investigated the JOA
      Back Pain Evaluation Questionnaire (JOABPEQ) to evaluate several aspects of low
      back pain in patients. The score includes five categories (25 items) selected
      from the Roland Morris Disability Questionnaire and Short Form 36, and a visual
      analogue scale. Japanese physicians have recently used these scores to evaluate
      back pain; however, the efficacy has not been fully explored in large-scale
      studies. In the current study, we used the JOABPEQ to evaluate lumbar spinal
      disease in 555 patients (with lumbar disc herniation, lumbar spinal stenosis, and
      lumbar disc degeneration/spondylosis) in multiple spine centers and compared the
      results based on age, sex, and type of disease. METHODS: A total of 555 patients
      who had low back or leg pain were selected in 22 hospitals in Chiba Prefecture.
      Spine surgeons diagnosed their disease type based on symptoms, physical
      examination, radiography images, and magnetic resonance imaging. In all, 486
      patients were diagnosed with spinal stenosis (239 patients), disc
      degeneration/spondylosis (143 patients), or disc herniation (104 patients). The
      other 69 patients were diagnosed with spondylolysis (16 patients) or other
      diseases (53 patients). The pain score in all patients was evaluated using the
      JOABPEQ (from 0 to 100, with 0 indicating the worst pain). RESULTS: The age of
      the patients was 56.1 +/- 13.3 years (mean +/- SD); the age of patients in the
      disc herniation and disc degeneration/spondylosis group was significantly lower
      than that in the spinal stenosis group. The average JOABPEQ scores in all
      patients were, for low back pain, 47.1; lumbar function, 53.6; walking ability,
      54.8; social life function, 48.7; and mental health, 48.3. The low back pain
      score in men was significantly worse than that in women. In contrast, the mental
      health score in women was significantly higher than that in men. The low back
      pain score in patients <40 years old and the walking ability score in patients
      >65 years old were significantly lower than those scores in other patients. Based
      on the disease type, low back pain, lumbar function, social life function, and
      mental health scores for patients with disc herniation were significantly worse
      than for those with spinal stenosis. CONCLUSION: JOABPEQ scores were evaluated
      for several lumbar diseases. The average of five categories of JOABPEQ scores in
      all patients was similarly distributed. However, the average scores in the five
      categories were significantly different depending on age, sex, and type of
      disease. Compared with prior mass data (baseline data on the observational cohort
      of the Spine Patient Outcomes Research Trial in the United States), many data
      were similar based on the type of disease in the current study. Furthermore, the
      JOABPEQ is easy to use compared with the SF-36. Hence, we concluded that the
      JOABPEQ could be used worldwide as a tool for evaluating low back pain.

PMID- 20151257
TI  - Incidence of complications associated with spinal endoscopic surgery: nationwide
      survey in 2007 by the Committee on Spinal Endoscopic Surgical Skill Qualification
      of Japanese Orthopaedic Association.
AB  - BACKGROUND: This report was conducted to elucidate the current status of spinal
      endoscopic surgery and relevant incidents through analysis of the results of a
      questionnaire survey conducted in 2007 by the Committee on Spinal Endoscopic
      Surgical Skill Qualification of the Japanese Orthopaedic Association (JOA).
      METHODS: Questionnaire forms were sent to 2011 training facilities nationwide
      certified by the JOA, and 1082 of these facilities returned the filled
      questionnaires (response rate 53.8%). Of these facilities, 257 (23.8% of the
      responding facilities) undertook spinal endoscopic surgery in 2007. These
      institutions were asked to fill in the survey form with the details of the
      operations and relevant incidents as well as the incident levels. RESULTS: In
      total, the 257 facilities performed 6239 spinal endoscopic surgeries during 2007.
      Posterior spinal endoscopic surgery constituted most of the operations (6217
      cases, 98.2%) including 4336 cases of microendoscopic discectomy (MED), 1273
      cases of microendoscopic laminectomy or fenestration, and 379 cases of
      transforaminal or posterior lumbar interbody fusion. The total number of
      incidents was 133 (2.13%). The numbers of incidents by operative method were 75
      (56.4%) during MED, 57 (42.9%) during microendoscopic laminectomy or
      fenestration, and 1 (0.8%) during interbody fusion. Of 133 incidents, dural tear
      occurred in 99 (74.4%), injury of the cauda equina or a nerve root in 7 (5.3%),
      facet fracture in 7 (5.3%), hematoma and wrong level in 6 each (4.5%), and wrong
      side and bedsore in 1 each (0.8%). The incident level was level 1 in 6, level 2
      in 24, level 3a in 82, level 3b in 16, level 4 in 5, and level 5 (fatal) in 0.
      CONCLUSIONS: The results of this survey revealed an increasing trend of spinal
      endoscopic surgery and a decreasing trend of the complication rates. The
      complication rates of spinal endoscopic surgery were not higher than those of
      conventional surgery, indicating the safety of this surgical method.

PMID- 20151258
TI  - Comparison of cervical spinal canal diameter between younger and elder
      generations of Japanese.
AB  - BACKGROUND: Cervical myelopathy is more common among Japanese than Westerners.
      The shorter anteroposterior diameter of the cervical spinal canals (AP diameter)
      is its probable cause. In recent years, builds of younger Japanese have become
      larger and been approaching those of Westerners. The purpose of this study was to
      investigate whether the cervical spinal canal had enlarged in the younger
      Japanese as well as any cross-sectional improvement in their builds. METHODS: The
      subjects included 300 men and 300 women who were healthy and without symptoms
      related to the cervical spine. They were divided into six age groups at 10-year
      intervals from the twenties to the seventies. Height, body weight, and arm span
      were measured as physical factors. Using lateral dynamic radiographs of the
      cervical spine, the AP diameter from C3 to C6 in the neutral position and
      Penning's jaw diameter in extension (jaw diameter) from C2/3 to C5/6 were
      measured. The number of trapezoid-shaped vertebral bodies with a thickened
      posterior margin were also counted as such thickening might be one of the causes
      of spinal canal narrowing. Statistical analysis was performed for the following
      associations in both sexes: (1) age and physical factors; (2) age and the AP
      diameter; (3) age and jaw diameter; and (4) the difference of the AP diameter of
      the canal within and outside the trapezoid-shaped deformity of the vertebral
      body. RESULTS: In both men and women, the younger generations statistically had a
      larger height, arm span, and AP diameter. Older generations showed a
      significantly narrower jaw diameter at all measured spinal levels in both sexes.
      Trapezoid-shaped vertebral bodies were found in 3.5% of the men and in 1.3% of
      the women in their fifties, sixties, and seventies, which statistically had no
      effect on the AP diameter being wider in the younger generations. CONCLUSIONS:
      Younger generations had larger builds and a wider canal of the cervical spine. A
      narrow spinal canal is a fundamental risk factor for cervical myelopathy.
      Therefore, cervical myelopathy might be expected to decrease in Japan in the near
      future when the present younger generations have aged.

PMID- 20151259
TI  - Ifosfamide encephalopathy associated with chemotherapy for musculoskeletal
      sarcomas: incidence, severity, and risk factors.
AB  - BACKGROUND: Ifosfamide encephalopathy is a central nervous system toxicity that
      occurs in patients treated with ifosfamide. Although it has been reported in
      European and American patients with various carcinomas, there have been no
      published reports regarding ifosfamide encephalopathy in Asian patients with bone
      and soft tissue sarcomas. METHODS: We retrospectively examined the incidence,
      severity, and risk factors of ifosfamide encephalopathy in 61 Japanese patients
      with bone and soft tissue sarcomas at our institution. RESULTS: Ifosfamide
      encephalopathy occurred in 17 of 61 patients (31.2%) to whom ifosfamide was
      administered and in 29 of 214 ifosfamide treatment courses (13.6%). The most
      common symptoms of encephalopathy were "confusion," "somnolence," and "mood
      alteration - agitation." Severe encephalopathy occurred only in patients who
      received ifosfamide at doses >or=9 g/m(2). A history of cisplatin use was
      identified as a significant risk factor for the development of ifosfamide-induced
      encephalopathy. CONCLUSIONS: Because of the risk of severe encephalopathy, we
      conclude that patients who have previously received cisplatin or who receive
      ifosfamide at doses >or=9 g/m(2) require strict monitoring.

PMID- 20151260
TI  - Treatment outcome of enchondroma by simple curettage without augmentation.
AB  - BACKGROUND: Simple curettage for enchondroma without augmentation, known to lead
      to spontaneous bone consolidation at the curettage site, is a potential standard
      treatment for this condition. However, few detailed data comparing the results of
      this technique with conventional methods including reconstruction are available,
      and the relation between the postoperative completion period for bone
      consolidation and preoperative independent variables is not known. METHODS: The
      subjects included 38 patients with enchondroma treated with simple curettage
      without augmentation. A historical group of patients with enchondroma treated
      with hydroxyapatite reconstruction was enrolled as controls. Treatment outcomes,
      including perioperative complications (e.g., infection, functional loss,
      recurrence, postoperative fracture), were surveyed. Differences in the period
      needed for bone formation among the patient groups defined by various
      preoperative patient conditions were also analyzed. RESULTS: The follow-up period
      ranged from 12 to 60 months (average 24.3 months). During the follow-up period,
      no surgery-related complications occurred. Bone formation was confirmed in all
      cases 3-20 weeks (average 6.5 weeks) postoperatively. Tumor size represented by
      two-dimensional measurements was significantly correlated with the bone formation
      period. Polycystic lesions required a prolonged postoperative bone formation
      period compared with monocystic lesions. The bone formation period did not
      significantly differ between the simple curettage group and the historical
      control group. CONCLUSIONS: Simple curettage without augmentation proved to be a
      safe, promising modality for the treatment of small enchondromas in the hand and
      foot.

PMID- 20151261
TI  - Measurement of subclavicular pressure on the subclavian artery and brachial
      plexus in the costoclavicular space during provocative positioning for thoracic
      outlet syndrome.
AB  - BACKGROUND: Thoracic outlet syndrome is thought to be caused by compression of
      the brachial plexus or subclavian artery in the interscalene, costoclavicular, or
      subcoracoid space. Some provocative tests are widely used for diagnosing thoracic
      outlet syndrome. However, whether provocative positions actually compress the
      neurovascular bundle in these spaces remains unclear. The purpose of this study
      was to investigate the possibility of neurovascular bundle compression in the
      costoclavicular space by measuring the pressure applied to the brachial plexus
      and subclavian artery in provocative positions. METHODS: Bilateral shoulders of
      eight fresh-frozen transthoracic human cadavers with no obvious anatomical
      abnormalities were used in this study. There were three female and five male
      cadavers with a mean age of 81.7 years (range 72-90 years). The pressure on the
      brachial plexus and subclavian artery between the clavicle and first rib were
      measured using a 0.13-mm thin pressure sensor in each of four provocative
      positions (depressed position, alternative Eden position, throwing position,
      Wright position). RESULTS: Nerve contact pressure was increased in seven
      shoulders in the Wright position (2.87 +/- 3.13 N/cm(2); range 0.81-9.76
      N/cm(2)). The frequency of nerve compression in the Wright position was
      significantly higher when compared to that in the other three limb positions (P =
      0.018). Artery contact pressure was increased in three shoulders in the Wright
      position (mean 0.59 +/- 0.13 N/cm(2); range 0.45-0.7 N/cm(2)). As was the case
      with nerve compression, the frequency of compression tended to be higher for the
      Wright position, but no significant difference was seen. CONCLUSIONS: In four of
      eight specimens with no obvious anatomical abnormalities, the brachial plexus was
      compressed in the costoclavicular space in the Wright position. The Wright
      position thus may be a useful position for inducing nerve compression in the
      costoclavicular space.

PMID- 20151262
TI  - Biomechanical evaluation of different anterior cruciate ligament fixation
      techniques for hamstring graft.
AB  - BACKGROUND: A number of anterior cruciate ligament (ACL) fixation techniques are
      currently in use. Slippage or failure of the graft by excessive loading or
      aggressive rehabilitation may result in an unstable knee. Load and slippage of
      the ACL graft varies according to the fixation technique used. METHODS: Graft
      slippage, load to failure, and stiffness were evaluated using an animal model.
      Six soft tissue ACL fixation techniques and bone cement as a fixation device were
      tested: group A, Endo Button CL-Bio RCI; group B, Swing Bridge-Evolgate; group C,
      Rigidfix-Intrafix; group D, Bone Mulch-Washer Lock; group E, Transfix-Retroscrew;
      group F, Transfix-Deltascrew; group G, Kryptonite bone cement. Maximum failure
      load, stiffness, and slippage at the 1st and 1000th cycles and mode of failure
      were evaluated. RESULTS: The maximum failure load was significantly higher in
      group B (1030 N) and significantly lower in group E (483 N) than in the others.
      The stiffness of group B (270 N/mm) was significantly higher than the others. As
      for the mode of failure, group C showed failure in the femoral side in all tests
      (four device ruptures and two tendon ruptures on the femoral side). All failures
      of the other groups occurred on the tibial side except one test in group A. All
      failures in group G were due to slippage of the tendons. CONCLUSION: Load to
      failure and stiffness was significantly different between the ACL fixation
      techniques. All but one of the fixation techniques showed sufficient properties
      for adequate postoperative rehabilitation. Bone cement used as a fixation device
      in soft tissue grafts did not seem to provide adequate initial fixation suitable
      for early rehabilitation after ACL reconstruction.

PMID- 20151263
TI  - Initial fixation of a finite element model of an AI-Hip cementless stem evaluated
      by micromotion and stress.
AB  - BACKGROUND: This study investigated issues related to initial stability after
      stem fixation. Finite element models of the AI-Hip cementless stem were
      constructed for computer simulation. METHODS: Analysis was performed after
      implantation of two types of cementless hip stem for clinical use; and
      micromotion and stress were then calculated. Boundary and initial conditions were
      (1) rigid contact of the distal end of the model femur with a rigid base; (2) a
      stepping load of 1800 N was applied to the proximal top of the stem; (3) a load
      of 1440 N was pulled from the greater trochanter of the femur as muscle force;
      (4) a torsion load of 18.9 Nm was applied to the proximal femur as the
      intrarotation. RESULTS: Relative micromotion of the AI-Hip cementless stem showed
      a value as low as that of a conventional stem. The calculated von Mises stress
      was below the level that would cause destruction of the femur and stem.
      CONCLUSIONS: Based on the relative micromotion and von Mises stress level, the AI
      Hip cementless stem showed initial stability. The present experimental results
      should be compared with those obtained in clinical practice.

PMID- 20151264
TI  - Omental free-tissue transfer following infected total knee arthroplasty with
      granuloma formation.

PMID- 20151265
TI  - Mazabraud's syndrome with solitary myxoma and monostotic fibrous dysplasia.

PMID- 20151266
TI  - Low-grade dedifferentiated liposarcoma of the neck: magnetic resonance imaging
      and pathological correlation.

PMID- 20151267
TI  - Simultaneous bilateral Salter-Harris type II injuries followed by unilateral
      Salter-Harris type III injury of the proximal tibia in an adolescent with
      osteogenesis imperfecta.

PMID- 20151268
TI  - Mutation spectrum of the CYP1B1 gene for congenital glaucoma in the Japanese
      population.
AB  - PURPOSE: Mutations of the CYP1B1 gene cause primary congenital glaucoma (PCG),
      Peters anomaly, and juvenile open-angle glaucoma (JOAG). The aim of this study
      was to determine the spectrum and role of the CYP1B1 gene in Japanese patients
      with PCG or JOAG. METHODS: Genomic DNA was extracted from the leukocytes of 18
      unrelated patients with PCG and 21 unrelated patients with JOAG. All of the
      patients developed high intraocular pressure (IOP) before the age of 35 years.
      One hundred unrelated healthy adults with normal IOP were examined in the same
      way. The three exons of the CYP1B1 gene were amplified by polymerase chain
      reaction and directly sequenced. RESULTS: Mutational screening and sequence
      analyses of the CYP1B1 gene revealed four mutations in four patients with PCG:
      p.Asp192Val, c.4776insAT, p.Val364Met, and p.Asp430Glu. The first three mutations
      have been reported in other Japanese PCG patients, but Asp430Glu is a new
      mutation. No mutations were found in the CYP1B1 gene of the JOAG patients.
      CONCLUSIONS: PCG in approximately 20% of Japanese patients may be associated with
      CYP1B1 mutations, but JOAG is not. The three mutations p.Asp192Val, c.4776insAT,
      and p.Val364Met appear to be common in the Japanese population and might be
      useful in genetic screening for PCG.

PMID- 20151269
TI  - Effects of switching to SofZia-preserved travoprost in patients who presented
      with superficial punctate keratopathy while under treatment with latanoprost.
AB  - PURPOSE: To investigate the effects of switching to SofZia-preserved travoprost
      (TRV) on superficial punctate keratopathy (SPK) observed in patients using
      benzalkonium chloride (BAC)-preserved latanoprost (LAT). METHODS: Patients with
      either primary open-angle glaucoma or ocular hypertension treated with LAT for at
      least 1 month who presented with SPK participated in this prospective,
      multicenter, open-label uncontrolled study. After the switch from LAT to TRV,
      patients were monitored at 2 weeks and at 1, 2, and 3 months. The use of
      concomitantly employed ophthalmic solutions was continued during the observation
      period. The intensity of SPK in each of five areas defined on the cornea was
      scored on a standard scale. Repeated measurements were tested with a linear mixed
      model. RESULTS: Of the 48 patients enrolled, 45 patients completed the study.
      After the switch to TRV, the mean SPK score in the whole cornea decreased
      significantly at every observation point (P < 0.0001 at each point) while
      intraocular pressure did not change significantly. Throughout the observation
      period, the SPK score tended to be higher in patients using a larger number of
      concomitant medications that contained BAC. CONCLUSION: Switching to TRV improved
      SPK observed in a population using LAT, likely because of a decrease in exposure
      to BAC.

PMID- 20151270
TI  - Epidermal nevus syndrome associated with anterior scleral staphyloma and ectopic
      bone and cartilaginous intraocular tissue.
AB  - BACKGROUND: Epidermal nevus syndrome encompasses a group of congenital
      neurocutaneous anomalies characterized by epidermal nevi in association with
      cerebral, ocular, and skeletal abnormalities. We report herein the case of a
      Japanese girl with epidermal nevus syndrome associated with complex ocular
      choristoma and discuss the histopathological findings. CASE: A mass lesion was
      noted on the left eyeball of a newborn Japanese girl. The lesion appeared to be a
      scleral staphyloma. Linear and diffuse acanthoses were also apparent on the face.
      Skin biopsy revealed an epidermal nevus. Histopathological examination of the
      enucleated left eyeball demonstrated that extremely thin sclera adjacent to the
      corneal limbus resulted in anterior staphyloma, and ectopic osteocartilaginous
      tissues were present in the posterior sclera. CONCLUSION: Epidermal nevus
      syndrome associated with complex ocular choristoma was diagnosed. The anterior
      staphylomatous lesion observed in this case has not been reported previously.

PMID- 20151271
TI  - Comparison of patients with ocular tuberculosis in the 1990s and the 2000s.
AB  - PURPOSE: To compare clinical findings in patients with ocular tuberculosis
      experienced during two different decades. METHODS: Thirty-four patients with
      ocular tuberculosis were divided into two groups: a 1990s group (n = 18) and a
      2000s group (n = 16), according to the dates of their first outpatient visit. The
      clinical profiles of the two groups were then compared. RESULTS: More cases of
      the 1990s group had complications involving extraocular tuberculosis than those
      of the 2000s group. While various ophthalmic manifestations were observed
      clinically in the 1990s group, all retinal periphlebitis cases presented in the
      2000s group. The proportion of patients who received antituberculous treatment
      was higher in the 1990s group, but the proportion who received oral
      corticosteroid therapy did not differ between the two periods. However, more
      patients underwent laser photocoagulation in the 2000s group. The percentage of
      eyes with final visual acuity better than 20/20 increased in the 2000s group.
      CONCLUSIONS: The clinical outcome of patients with ocular tuberculosis was
      improved in the 2000s group, which may be attributable to the increase in active
      use of laser photocoagulation therapy.

PMID- 20151272
TI  - Analysis of bicanalicular nasal intubation in the repair of canalicular
      lacerations.
AB  - PURPOSE: To analyze the outcomes (success, failure) and complications of surgical
      repair of canalicular lacerations by bicanalicular nasal intubation in a series
      of patients treated over a 7-year period. METHODS: The case records of 98
      patients undergoing surgical repair of canalicular lacerations were
      retrospectively reviewed. Patient characteristics and results of the surgical
      repair were analyzed to identify factors that may influence the outcomes. Two
      groups (success and failure) were statistically compared with the Mann-Whitney U
      test for scale variables and with Fisher's exact test for categorical variables.
      RESULTS: Of the 98 patients, 78 (79.6%) had patency after irrigation (anatomic
      success) and 83 (84.7%) were asymptomatic (functional success). Patients age,
      sex, injury location, anesthetic methods, and timing of surgical repair were not
      significantly associated with the postoperative patency of the lacerated
      canaliculus. Having a stent left for more than 90 days was significantly
      associated with restoration of the canalicular anatomy (P < 0.01). Patients with
      postoperative anatomic patency had a significantly lower rate of symptomatic
      epiphora than patients with anatomic obstruction (P < 0.001). Symptomatic
      epiphora was significantly more frequent in patients with combined upper and
      lower canalicular injuries (P < 0.01). CONCLUSION: Our results suggest that
      retaining bicanalicular silicone nasal intubation for more than 90 days can
      provide satisfactory results in restoring both canalicular anatomy and function.
      With an experienced operating team, repair of canalicular lacerations can be
      delayed for up to 11 days. However, patients with combined upper and lower
      canalicular lacerations are at an increased risk of developing postoperative
      symptomatic epiphora.

PMID- 20151273
TI  - Oscillatory potentials with repeated-flash electroretinography.
AB  - PURPOSE: To study the influence of retinal adaptation on oscillatory potential
      (OP) using repeated-flash electroretinography. METHODS: Subjects were 28 adult
      eyes with normal retinas. Four stimuli (four flashes) of white light from a light
      emitting diode built into a contact lens that also served as the recording
      electrode were presented at 5-s intervals after 30 min of dark adaptation (DA)
      and then after 10 min of light adaptation (LA). Recordings were made without
      background light. RESULTS: Four OPs (O1, O2, O3, and O4) were recordable. After
      DA, amplitudes of O1 and O4 decreased with subsequent flashes, whereas those of
      O2 increased after the second flash. After LA, amplitudes of O3 and O4 were
      smaller than after DA. CONCLUSIONS: Amplitude and implicit time of OPs were
      influenced by retinal adaptation. Among all OPs, O2 showed unique characteristics
      in course of retinal adaptation.

PMID- 20151274
TI  - Peripapillary retinal nerve fiber layer thickness in normal Japanese eyes
      measured with optical coherence tomography.
AB  - PURPOSE: To measure peripapillary retinal nerve fiber layer (RNFL) thickness in
      healthy Japanese individuals using optical coherence tomography (OCT). METHODS:
      OCT was used to measure the eyes of 460 healthy Japanese volunteers aged 20 to
      84. One eye of each individual was selected for the statistical analysis.
      RESULTS: the average circumpapillary (cp) rnfl thickness of all eyes was 111.8 +/
      10.0 microm. a statistically significant negative correlation was found between
      the average cp rnfl thickness and age. for every decade increase in age, the
      average cp rnfl thickness decreased by approximately 2.2 microm. the average cp
      rnfl thickness was estimated to decrease by 0.18% per year. the age-associated
      reduction in cp rnfl thickness was particularly noted in the inferior-temporal to
      superior-temporal segments: CONCLUSIONS: Age-related cp RNFL loss varies
      according to segment. When OCT is used to evaluate cp RNFL thickness, regional
      and age-related differences need to be taken into consideration.

PMID- 20151275
TI  - Reproducibility of peripapillary retinal nerve fiber layer thickness with
      spectral domain cirrus high-definition optical coherence tomography in normal
      eyes.
AB  - PURPOSE: To assess the reproducibility of the new spectral domain Cirrus high
      definition optical coherence tomography (HD-OCT; Carl Zeiss Meditec, Dublin, CA,
      USA) for analysis of peripapillary retinal nerve fiber layer (RNFL) thickness in
      healthy eyes. METHODS: Thirty healthy Korean volunteers were enrolled. Three
      optic disc cube 200 x 200 Cirrus HD-OCT scans were taken on the same day in
      discontinuous sessions by the same operator without using the repeat scan
      function. The reproducibility of the calculated RNFL thickness and probability
      code were determined by the intraclass correlation coefficient (ICC), coefficient
      of variation (CV), test-retest variability, and Fleiss' generalized kappa
      (kappa). RESULTS: Thirty-six eyes were analyzed. For average RNFL thickness, the
      ICC was 0.970, CV was 2.38%, and test-retest variability was 4.5 microm. For all
      quadrants except the nasal, ICCs were 0.972 or higher and CVs were 4.26% or less.
      Overall test-retest variability ranged from 5.8 to 8.1 microm. The kappa value of
      probability codes for average RNFL thickness was 0.690. The kappa values of
      quadrants and clock-hour sectors were lower in the nasal areas than in other
      areas. CONCLUSIONS: The reproducibility of Cirrus HD-OCT to analyze peripapillary
      RNFL thickness in healthy eyes was excellent compared with the previous reports
      for time domain Stratus OCT. For the calculated RNFL thickness and probability
      code, variability was relatively higher in the nasal area, and more careful
      analyses are needed.

PMID- 20151276
TI  - Asymptomatic extramacular abnormal choroidal lesions in eyes with macular
      polypoidal choroidal vasculopathy.
AB  - PURPOSE: To classify polypoidal choroidal vasculopathy (PCV) presenting with both
      extramacular and macular lesions according to location and clinical
      manifestations. METHODS: We performed a retrospective analysis of 29 eyes
      presenting with both extramacular and macular PCV lesions by indocyanine green
      angiography. The patients were classified according to the location of the
      extramacular lesions and clinical manifestations. RESULTS: PCV locations were
      identified as peripapillary (32.1%), superior (10.7%) or inferior (17.9%) to the
      optic disc, superior (14.3%) or inferior (7.1%) temporal arcade, temporal to the
      macula (10.7%), and nasal to the optic disc (7.1%). Clinical manifestations were
      identified as polyp (10.7%), branching vascular networks (42.9%), pigment
      epithelial detachment (PED) (17.9%), polyp and branching vascular networks
      (7.1%), polyp and PED (14.3%), and all three (7.1%). CONCLUSIONS: PCV showed
      extramacular lesions with various clinical manifestations discontinuous from the
      macular lesions.

PMID- 20151277
TI  - Restoration of outer segments of foveal photoreceptors after resolution of
      central serous chorioretinopathy.
AB  - PURPOSE: To study morphologically and functionally the prognosis of damaged outer
      segments of the foveal photoreceptor layer in eyes with resolved central serous
      chorioretinopathy (CSC). METHODS: We studied retrospectively the medical records
      of 70 patients (74 eyes) with resolved CSC. Optical coherence tomography was used
      to detect the junctions between inner and outer segments of the photoreceptors
      (IS/OS) as a hallmark of the integrity of the outer photoreceptor layer. RESULTS:
      In 53 eyes (71.6%), the IS/OS line was clearly detected beneath the fovea
      immediately after resolution of the retinal detachment, with good visual acuity
      (VA). In the remaining 21 eyes (28.4%), however, the foveal IS/OS line could not
      be detected shortly after resolution of CSC, and VA was variable, ranging from
      0.1 to 1.5 (median, 0.9). Of these 21 eyes, 15 had a follow-up examination with
      OCT, and in four the foveal IS/OS line was not detected at the follow-up and
      vision in these eyes remained poor. However, nine eyes showed recovery of the
      foveal IS/OS line during follow-up, and these eyes had substantial visual
      recovery. CONCLUSIONS: Immediately after resolution of active CSC, although the
      IS/OS line cannot be detected beneath the fovea, it often shows restoration over
      time, with visual recovery, though in some eyes no restoration takes place and
      the prognosis remains poor.

PMID- 20151278
TI  - Possible effects of internal limiting membrane peeling in vitrectomy for macular
      vein occlusion.
AB  - PURPOSE: To evaluate the effect of pars plana vitrectomy (PPV) either with or
      without internal limiting membrane (ILM) peeling for macular edema associated
      with macular vein occlusion (MVO). METHODS: In this retrospective,
      interventional, comparative case series study, 41 patients (41 eyes) underwent
      PPV either with or without ILM peeling for macular edema due to MVO. Twenty-eight
      eyes without ILM peeling (PPV alone) were compared with 13 eyes with ILM peeling
      (ILM-off). The main outcome measures were best-corrected visual acuity (BCVA) and
      foveal thickness, evaluated by optical coherence tomography. RESULTS: Baseline
      demographic characteristics of the two groups were similar. Postoperative follow
      up period ranged from 12 to 53 months (mean, 27.9 months). The postoperative mean
      BCVA improved and foveal thickness decreased significantly in both groups. The
      difference in BCVA between the two groups was not significant at any time point.
      The mean foveal thickness in the ILM-off group was thicker than that in the PPV
      alone group during the follow-up period. No patient had severe intraoperative or
      postoperative complications. CONCLUSION: PPV either with or without ILM peeling
      may improve the anatomical and functional outcomes of macular edema secondary to
      MVO. Removal of the ILM does not appear to affect visual outcome; however, it may
      not reduce the foveal thickness as much as PPV alone.

PMID- 20151279
TI  - The relationship between preoperative clinical scores and immunohistological
      evaluation of surgically resected tissues in chronic severe ocular surface
      diseases.
AB  - PURPOSE: To clarify the relationship between clinical symptoms and histological
      status in patients with ocular cicatricial pemphigoid (OCP) and Stevens-Johnson
      syndrome (SJS). METHODS: Clinical symptoms of four OCP and eight SJS patients in
      the chronic phase were scored with our recently proposed grading system. The
      histological status of the pannus tissue removed from the corneal surface during
      surgery was investigated using immunohistological techniques. RESULTS: All
      participants showed total loss of the palisades of Vogt and conjunctivalization
      of the entire corneal surface. All pannus tissues expressed the conjunctival
      epithelium marker CK4/13. The pannus tissue in clinically keratinized SJS
      expressed skin epidermal major cytokeratins, but the tissues of nonkeratinized
      SJS did not. CONCLUSIONS: Clinical observation and the use of our recently
      proposed grading system agreed with the immunohistological status with respect to
      keratinization, cell proliferation, and corneal/conjunctival cell typing. These
      findings facilitate our understanding of the pathogenesis of OCP and SJS, and
      will hopefully contribute to the development of future treatment strategies and
      improve predictions of the postoperative prognosis of ocular surface
      reconstruction in patients with OCP and SJS.

PMID- 20151280
TI  - Cloning and characterization of cell strains derived from human corneal stroma
      and sclera.
AB  - PURPOSE: To establish human corneal stroma- and sclera-derived cells as models
      for studying diseases of the anterior segment of the eye. METHODS: Using a
      recombinant retrovirus system, we transfected human papilloma virus 16 E6 and E7
      (HPV16 E6/E7) into human corneal stroma- and sclera-derived cells. The primary
      cells and established cell strains were characterized by assessing the mRNA
      expression of collagen, matrix metalloproteinase, and tissue inhibitor of
      metalloproteinase by reverse transcription-polymerase chain reaction. We also
      examined the effects of inflammatory cytokines on hyaluronan synthase expression
      and hyaluronan products. RESULTS: Both a corneal stroma-derived cell strain, Cs3,
      and a sclera-derived cell strain, Sc1, were obtained, and both cell strains could
      be passaged up to 25 times. The mRNA expression pattern observed in the primary
      cells was identical to that observed in the cell strains. Hyaluronan synthase 1
      and 2 mRNAs were increased by transforming growth factor beta and platelet
      derived growth factor BB. Significant differences were observed between the
      hyaluronan products with and without cytokine treatment. CONCLUSION: Cell strains
      derived from corneal stroma and sclera fibroblast cells can be established using
      HPV16 E6/E7 immortalized genes of the same origin. The phenotypic cell
      characteristics did not change after transfection, immortalization, or successive
      passages in culture.

PMID- 20151281
TI  - Elevation of surfactant protein D, a pulmonary disease biomarker, in the sera of
      uveitis patients with sarcoidosis.
AB  - PURPOSE: Surfactant protein D (SP-D) is found in the epithelial cells of multiple
      mucosal surfaces. It is commonly used to diagnose and screen for pulmonary
      diseases. In the present study, serum levels of SP-D were measured in patients
      with uveitis to ascertain whether SP-D is a clinically useful laboratory
      parameter to diagnose sarcoidosis. METHODS: Sera were obtained from 81 patients
      with sarcoidosis, 16 patients with Behcet disease, 40 patients with HLA-B27
      associated uveitis, 50 patients with Vogt-Koyanagi-Harada (VKH) disease, and 33
      healthy volunteers. Serum SP-D levels were quantified with an SP-D enzyme
      immunoassay kit. RESULTS: In the healthy control subjects, the average serum SP-D
      level was 39.70 ng/ml; in the uveitis patients with sarcoidosis, the mean serum
      SP-D level was 57.0 ng/ml, and in the uveitis patients with other etiologies the
      mean levels were 38.63 ng/ml for Behcet disease, 38.18 ng/ml for HLA-B27
      associated uveitis, and 31.32 ng/ml for the VKH patients. The average serum SP-D
      levels of patients with sarcoidosis were significantly higher than those of
      patients with any other uveitis etiologies or healthy controls (P < 0.01).
      CONCLUSIONS: SP-D may be a less invasive and less expensive laboratory
      examination for sarcoidosis screening. SP-D should be considered as a new
      laboratory parameter for the diagnosis of uveitis and sarcoidosis.

PMID- 20151282
TI  - Expression of Epiplakin1 in the developing and adult mouse retina.
AB  - PURPOSE: To assess the expression of Epiplakin1 (Eppk1) in the developing and
      adult mouse retina. METHODS: Eppk1 expression was examined using reverse
      transcription-polymerase chain reaction (RTPCR) analysis and immunoblot analysis.
      The Eppk1 expression pattern was examined by immunohistochemical analysis in
      embryonic and adult C57BL/6J mice. RESULTS: Both Eppk1 mRNA and protein were
      detected in adult mouse retina. Eppk1 was expressed in nestin-positive neural
      progenitor cells in the embryonic retina. In adults, Eppk1 was expressed in
      retinal ganglion cells, bipolar cells, and Muller glial cells. CONCLUSIONS: These
      results suggest that Eppk1 is expressed both in embryonic and adult retina and
      may be involved in retinal development.

PMID- 20151283
TI  - Mutations in the XLRS1 gene in Thai families with X-linked juvenile
      retinoschisis.
AB  - PURPOSE: To identify genetic mutations of the XLRS1 gene and to describe the
      ocular phenotypes in two unrelated Thai patients with X-linked juvenile
      retinoschisis. METHODS: Ophthalmic examination, including best-corrected visual
      acuity and fundus examination and photography, was performed in all participants.
      Electroretinography (ERG) and optical coherence tomography were performed when
      possible. All six exons of the XLRS1 gene were amplified, and mutation screening
      was determined by denaturing high-performance liquid chromatography and DNA
      sequencing. RESULTS: Two point mutations were identified, a novel missense
      mutation c.378A > G (p.D126G) in exon 5 and a reported mutation c.637C > T
      (p.R213W) in exon 6. The first proband with the p.D126G mutation developed
      vitreous hemorrhage in both eyes at age 7 months. Foveal and peripheral schisis
      with several inner layer holes were detected in both eyes. The second proband
      with the p.R213W mutation developed slightly blurred vision at age 10 years.
      Fundus examination showed numerous fine white dots at the macula without foveal
      or peripheral schisis. Electronegative ERG results were documented in both
      probands. CONCLUSIONS: A novel p.D126G mutation appeared to be associated with a
      severe phenotype with vitreous hemorrhage developing in infancy. Both intra- and
      interfamilial clinical variabilities were recognized in our patients.

PMID- 20151284
TI  - Changes in optic disc shape and size in two patients with suspected glaucoma
      during a two- and three-year follow-up period.

PMID- 20151285
TI  - Statistical analyses of ocular inflammatory diseases at Saitama Red Cross
      Hospital (2003-2007).

PMID- 20151286
TI  - Molecular identification by 16S rDNA sequencing using excised corneal tissues: a
      useful diagnostic tool for refractory keratitis.

PMID- 20151287
TI  - Expression of NG2-positive cells during optic neuritis.

PMID- 20151288
TI  - A case of cyclosporine-induced optic neuropathy with a normal therapeutic level
      of cyclosporine.

PMID- 20151289
TI  - A case of microcystic adnexal carcinoma.

PMID- 20151290
TI  - Retinal detachment with giant oral dialysis in an eye with congenital aniridia.

PMID- 20151291
TI  - Aqueous humor nitric oxide levels in patients with branch retinal vein occlusion.

PMID- 20151292
TI  - Uveal effusion syndrome caused by choroidal invasion of malignant lymphoma.

PMID- 20151293
TI  - Choroidal metastasis of renal cell carcinoma: a case report.

PMID- 20151298
TI  - A gene controlling the number of primary rachis branches also controls the
      vascular bundle formation and hence is responsible to increase the harvest index
      and grain yield in rice.
AB  - The quantitative trait locus controlling the number of primary rachis branches
      (PRBs) in rice was identified using backcrossed inbred lines of
      Sasanishiki/Habataki//Sasanishiki///Sasanishiki. The resultant gene was ABERRANT
      PANICLE ORGANIZATION 1 (APO1). Habataki-genotype segregated reciprocal
      recombinant lines for the APO1 locus increased both the number of PRB (12-13%)
      and the number of grains per panicle (9-12%), which increased the grain yield per
      plant (5-7%). Further recombination dividing this region revealed that different
      alleles regulated the number of PRB and the number of grains per panicle. The
      PRB1 allele, which includes the APO1 open reading frame (ORF) and the proximal
      promoter region, controlled only the number of PRB but not the number of grains
      per panicle. In contrast, the HI1 allele, which includes only the distal promoter
      region, increased the grain yield and harvest index in Habataki-genotype plants,
      nevertheless, the ORF expressed was Sasanishiki type. It also increased the
      number of large vascular bundles in the peduncle. APO1 expression occurred not
      only in developing panicles but also in the developing vascular bundle systems.
      In addition, Habataki plants displayed increased APO1 expression in comparison to
      Sasanishiki plants. It suggests that APO1 enhances the formation of vascular
      bundle systems which, consequently, promote carbohydrate translocation to
      panicles. The HI1 allele is suggested to regulate the amount of APO1 expression,
      and thereby control the development of vascular bundle systems. These findings
      may be useful to improve grain yield as well as quality through the improvement
      of translocation efficiency.

PMID- 20151300
TI  - Filtering FRAX.

PMID- 20151299
TI  - Protein kinase C-delta is involved in the inflammatory effect of IL-6 in mouse
      adipose cells.
AB  - AIMS/HYPOTHESIS: The aim of the study was to address the role of protein kinase C
      delta (PKCdelta) on phosphorylation of signal transducer and activator of
      transcription 3 (STAT3) and activation of inflammatory genes in response to IL-6
      in adipose cells. METHODS: Differentiated mouse 3T3-L1 adipocytes preincubated
      with the PKCdelta inhibitor rottlerin and mouse embryonic fibroblasts (MEFs)
      lacking PKCdelta were incubated with IL-6 and/or insulin. RNA was extracted and
      the gene expression was analysed by real-time PCR, while the proteins from total,
      nuclear and cytoplasmic lysates were analysed by immunoblotting. RESULTS:
      Inhibition of PKCdelta by rottlerin significantly reduced both Ser-727 and Tyr
      705 phosphorylation of STAT3. Consequently, nuclear translocation of STAT3 and
      the IL-6-induced gene transcription and protein release of the inflammatory
      molecule serum amyloid A 3 (SAA3) were reduced. Similarly, the IL-6-regulated
      gene transcription of Il-6 (also known as Il6) to Hp and the feedback inhibitor
      of IL-6, Socs3, were also attenuated by rottlerin. Furthermore, PKCdelta was
      found to translocate to the nucleus following IL-6 treatment and this was also
      reduced by rottlerin. In agreement with the effect of rottlerin, Pkcdelta (also
      known as Prkcd) ( -/- ) MEFs also displayed a markedly reduced ability of IL-6 to
      activate the transcription of Saa3, Hp, Socs3 and Il6 genes compared with wild
      type MEFs. These results correlated with a reduced nuclear translocation and
      phosphorylation of STAT3. CONCLUSIONS/INTERPRETATION: These results show that
      PKCdelta plays a key role in the inflammatory effect of IL-6 in adipose cells and
      may be a suitable target for novel anti-inflammatory agents.

PMID- 20151301
TI  - Emergent flexibility in motor learning.
AB  - We examined the effect of exploring redundant solutions during practice in
      enhancing the ability to flexibly use them to achieve a task goal. Three groups
      used different degrees of path redundancy to perform a virtual interception task
      in which they attempted to hit a stationary target by moving around a stationary
      obstacle. The low-variability group always practiced with the same position of
      the obstacle on all trials. The medium-variability and high-variability groups
      practiced with the obstacle in different positions within a range of 1 and 2 cm
      respectively. After eight blocks of practice, all participants were transferred
      to two tests: (a) a fixed obstacle test where the condition was the same as that
      practiced by the low-variability group, and (b) a variable obstacle test where
      the condition was the same as that practiced by the high-variability group.
      Results showed that the low-variability group had the most accurate performance
      both in the fixed obstacle and the variable obstacle test. The low-variability
      group showed the least path variability during the fixed obstacle test but was
      also able to adapt to the different positions of the obstacle during the variable
      obstacle test. It appears that flexibility in interceptive tasks is emergent from
      learning a particular task-relevant parameter related to the target location.

PMID- 20151302
TI  - Poor clinical outcome despite successful arterial recanalization. What went
      wrong? How can we do better?

PMID- 20151303
TI  - Pericardial single-patch repair of right coronary artery from aorto-left
      ventricular tunnel.
AB  - Aortico-left ventricular tunnel (ALVT) is a rare congenital paravalvar
      communication between the aorta and the left ventricle. This anomaly has been
      associated with the right coronary artery (RCA) arising directly from the tunnel.
      Surgical repair of this later condition is challenging and is usually undertaken
      by closure of the ventricular and aortic ends of the tunnel and transfer of the
      RCA. Regardless of the surgical technique, development of early and late aortic
      regurgitation (AR) remains a concern. We report a neonate with ALVT and the RCA
      coming off the tunnel that was successfully managed by closure of both ends of
      the tunnel, reinforcement of the annulus with autologous pericardium, and leaving
      the RCA perfused by way of the tunnel. After 6 months of follow-up, no AR has
      been shown on echocardiography.

PMID- 20151304
TI  - Assessment of colon motility using simultaneous manometric and functional cine
      MRI analysis: preliminary results.
AB  - PURPOSE: Gastrointestinal functional disorders are common symptoms. The
      evaluation of underlying colonic motility dysfunction is difficult due to lacking
      adequate examination techniques. Recently cine-magnetic resonance imaging (MRI)
      was introduced as imaging technique for visualizing colon motility. However, the
      correlation of MR-visible colonic-movements and real intraluminal movements was
      not demonstrated yet. Therefore, this feasibility study's purpose was to
      stimulate high amplitude propagated pressure waves (HAPPWs) by bisacodyl
      application under manometric control and to simultaneously identify them with
      cine-MRI. MATERIALS AND METHODS: Colonoscopically, a water-perfused 8-lumen-probe
      was placed in descending colon. Intraluminal pressure was recorded over time.
      After 90 min equilibration phase, MR exam at rest (HASTE-sequence, 1.5Tesla
      Avanto((r)), Siemens-Medical-Solutions) was performed. Consecutively, 10 mg
      bisacodyl were instilled via colonic probe to induce HAPPWs. Cine-MRI and
      manometry were performed simultaneously over 24 min. HAPPWs were defined as
      pressure waves with amplitude >50 mmHg and propagation over min. three side
      holes. MRI was analyzed for corresponding luminal changes of the referring
      colonic segment propagated aborally. RESULTS: Ten healthy volunteers (age:19-62
      years, 4 females, 6 males) were enrolled. Manometry identified 11 HAPPWs, most 9
      16 min post-stimulation. All HAPPWs were identified on MRI with corresponding
      luminal changes (100% sensitivity). CONCLUSIONS: In accordance with our study
      group's previous publications, these results show that cine-MRI allows not only
      for reliable HAPPWs' visualization using pharmalogical stimuli, but visualized
      colonic movements have 100% correlation to intraluminal pressure changes in
      manometry (gold-standard). This may be a first step to introduce cine-MRI for non
      invasive colon motility assessment in patients with functional gastro-intestinal
      disorders.

PMID- 20151305
TI  - Vascularized osteochondral graft from the medial femoral trochlea: anatomical
      study and clinical perspectives.
AB  - PURPOSE: Few donor sites for vascularized reconstruction of convex joint surfaces
      have been described. We studied the feasibility of a convex vascularized
      osteochondral graft harvested from the medial femoral condyle and trochlea, on an
      anatomical and practical point of view. METHODS: An injection-corrosion technique
      was used on 16 fresh cadaver specimens, and completed by a modified Spalteholz
      clearing. The extra- and intraosseous vascularization of the medial femoral
      condyle was systematized and the luminal diameter of the arteries was
      microscopically measured. Radii of curvature of the medial trochlea and of the
      carpal bones were measured on arthro-CT-scanner reconstructed images. RESULTS:
      The periosteal vessels of the medial condyle are responsible for the whole
      peripheral intraosseous vascularization, without any watershed region. They are
      fed by the articular branch of the descending genicular artery and/or the
      superomedial genicular artery. Several constant vascular axes can be found, and
      may serve as a pedicle for a vascularized osteochondral graft from the medial
      femoral trochlea. The radii of curvature of this graft do fit those of the
      proximal carpal row. A simple surgical approach is suggested. CONCLUSIONS: A
      vascularized graft harvested on the medial femoral trochlea is a technically
      feasible procedure that could represent a new reconstructive tool for convex
      joint surfaces. Osteonecrosis of the proximal pole of the scaphoid or Kienbock's
      disease are among several situations where such a graft could be beneficial.

PMID- 20151306
TI  - Composite likelihood-based inferences on genetic data from dependent loci.
AB  - The structure of dependence between neighboring genetic loci is intractable under
      some models that treat each locus as a single data-point. Composite likelihood
      based methods present a simple approach under such models by treating the data as
      if they are independent. A maximum composite likelihood estimator (MCLE) is not
      easy to find numerically, as in most cases we do not have a way of knowing if a
      maximum is global. We study the local maxima of the composite likelihood (ECLE,
      the efficient composite likelihood estimators), which is straightforward to
      compute. We establish desirable properties of the ECLE and provide an estimator
      of the variance of MCLE and ECLE. We also modify two proper likelihood-based
      tests to be used with composite likelihood. We modify our methods to make them
      applicable to datasets where some loci are excluded.

PMID- 20151307
TI  - Abstracts of the 4th European Conference on Head and Neck Oncology. Athens,
      Greece. March 4-6, 2010.

PMID- 20151309
TI  - Description of Lemuricola (Lemuricola) pongoi--male (Nematoda: Enterobiinae)
      parasitising orangutan Pongo abelii.
AB  - The study presents the first description of male specimen (allotype) of the
      pinworm species Lemuricola (Lemuricola) pongoi, parasitising Sumatran orangutan
      (Pongo abelii) from Sumatra (Indonesia). The male specimen morphology presents
      all features fully corresponding with diagnose of the genus and subgenus
      Lemuricola. We are agreeing that Protenterobius is synonymous with Lemuricola
      because the length of tail appendix in males is not a sufficient feature for
      separation of the genera or subgenera. For L. (L.) pongoi male are characteristic
      features: body length (4,803 microm), total oesophagus length (530), tail length
      (235), tip of tail length (188) and spicule length (90).

PMID- 20151308
TI  - Role of urinary biomarkers of N,N-dimethylformamide in the early detection of
      hepatic injury among occupational exposed workers.
AB  - AIM: To determine the sensitive and convenient biomarkers for the early detection
      of hepatic injury in N,N-dimethylformamide (DMF) exposed workers. METHODS:
      Seventy-nine individuals in a synthetic leather factory were investigated with
      questionnaire survey. The air samples, urine samples, and blood samples were
      collected at the specific time point. Airborne DMF and the urine metabolites of
      DMF were measured by gas chromatography (GC), high-performance liquid
      chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS).
      Traditional liver function tests and hepatic fibrosis parameters were performed
      by auto-chemistry analyzer and ELISA methods. RESULTS: The urine concentration of
      N-acetyl-S-(N-methylcarbamoyl)-cysteine (AMCC), one of the metabolites of DMF,
      was positively correlated with activities of liver function enzymes. About 60%
      subjects with urine AMCC concentration above 40 mg/g creatinine showed raised
      liver enzymes activities. In terms of hepatic fibrosis parameters, we found 4 of
      5 abnormal total serum bile acid (SBA) and 4 of 4 abnormal serum hyaluronidase
      (HA) among workers with higher amount of urine AMCC. CONCLUSION: Workers exposed
      to DMF with higher urine AMCC levels were more likely to develop liver diseases.
      In addition, SBA and HA have the potential to act as early indicators of toxic
      hepatic fibrosis activities for occupational health surveillance.

PMID- 20151310
TI  - [Preventive medication in migraine headache : Individualized clinical pathways].
AB  - With the introduction of the highly effective triptans in the treatment of acute
      migraine attacks, the significance of migraine prevention temporarily lost ground
      in the awareness of doctors and, even more so, patients. This was unjustified, as
      the increasing numbers of patients with triptan-overuse headache clearly
      demonstrated. Recent years have seen this trend reversed with a resurgence of
      migraine prevention. In daily practice the first question is whether migraine
      prevention is indeed indicated for the patient. If answered affirmatively, the
      next step is the intricate selection of the most promising agent for the patient.
      Treatment guidelines regularly updated by the relevant medical societies provide
      a general overview of the agents principally available according to the
      principles of evidence-based medicine. Yet, low compliance rates suggest that in
      practice implementation of these guidelines may have to be tailored to the
      patient in question. The treatment algorithm presented here tries to bridge the
      gulf between general treatment guidelines and the actual needs of the patient.
      From this, feasible clinical pathways are derived for individualized treatment.

PMID- 20151311
TI  - The cold hand sign in multiple system atrophy: skin perfusion revisited.
AB  - The cold hand sign (CHS) is a distinct feature of multiple system atrophy (MSA),
      but its pathophysiology is poorly understood. We, therefore, conducted a study to
      examine the skin temperature and the skin blood flow at rest and after local
      heating in 6 age-matched MSA patients with CHS (MSA + CHS), 18 MSA patients
      without CHS (MSA - CHS) and 13 patients with idiopathic Parkinson's disease (PD).
      Basal skin temperature and blood flow were significantly lower in MSA + CHS
      patients than in MSA - CHS or PD patients. Local heating induced a greater
      response in terms of amplitude in MSA + CHS compared to MSA - CHS and PD.
      Considering kinetics, skin blood flow increment per 1 degrees C was higher in MSA
      + CHS than MSA - CHS but was similar when compared to PD patients. Skin blood
      flow rate (change per second) did not differ among the groups. Our findings
      suggest that despite impaired basal skin perfusion, the skin vasomotor response
      to local heating is intact in MSA + CHS but disturbed in MSA - CHS. By measuring
      skin temperature and blood flow, the presence of CHS can be diagnosed in MSA
      patients. Further studies are necessary to understand regulation of skin
      perfusion in patients with extrapyramidal disease.

PMID- 20151312
TI  - Cemento-ossifying fibroma of jaws-correlation of clinical and pathological
      findings.
AB  - Cemento-ossifying fibroma (COF) belongs to the group of bone-related lesions of
      the oral cavity. The aim of this study was refine its histologic features and to
      correlate histopathological picture and clinical behavior of the tumor. The
      quantity of bone spherules, their cellularity, the existence of hemorrhage,
      inflammation, and endochondral ossification in the stroma of the tumor were
      analyzed and correlated with patients main symptoms of ten patients with COF. All
      patients had swelling that lasted between 3 and 20 months (mean 10.4 months).
      Other clinical symptoms were facial asymmetry, eye bulb protrusion, and teeth
      displacement. The evolution of the tumor was longer in the mandible (12.3 months)
      than in maxilla (9.5 months). The main histomorphological diagnostic criterion
      for COF was psammoma-like structures. In lesions with longer case history, the
      number of "psammomatoid" bodies was greater. In lesions with shorter course of
      the disease, their number was lower and stromal hemorrhage and inflammation were
      presented. One patient had secondary superposition of aneurysmal bone cyst in the
      prime COF of mandible. Histological appearance of COF may be influenced by the
      tumor evolution. A siginificant correlation between the clinical course of the
      disease and histological parameters has been certified.

PMID- 20151313
TI  - Viscoelastic properties of silica nanoparticle monolayers at the air-water
      interface.
AB  - We have investigated the rheological behaviour of silica nanoparticle layers at
      the air-water interface. Both compressed and deposited layers have been studied
      in Langmuir troughs and with a bicone rheometer. The compressed layers are more
      homogeneous and rigid, and the elastic response to continuous, step and
      oscillatory compression are similar, provided the compression is fast enough and
      relaxation is prevented. The deposited layers are less rigid and more
      viscoelastic. Their shear moduli deduced from the oscillatory uniaxial
      compression are much smaller than those deduced from pure shear deformation
      suggesting that the effective shear rate is smaller than expected in the
      compression measurements.

PMID- 20151314
TI  - Mitochondrial control of caspase-dependent and -independent cell death.
AB  - Mitochondria control whether a cell lives or dies. The role mitochondria play in
      deciding the fate of a cell was first identified in the mid-1990s, because
      mitochondria-enriched fractions were found to be necessary for activation of
      death proteases, the caspases, in a cell-free model of apoptotic cell death.
      Mitochondrial involvement in apoptosis was subsequently shown to be regulated by
      Bcl-2, a protein that was known to contribute to cancer in specific
      circumstances. The important role of mitochondria in promoting caspase activation
      has therefore been a major focus of apoptosis research; however, it is also clear
      that mitochondria contribute to cell death by caspase-independent mechanisms. In
      this review, we will highlight recent findings and discuss the mechanism
      underlying the mitochondrial control of apoptosis and caspase-independent cell
      death.

PMID- 20151315
TI  - Differential floral development and gene expression in grapevines during long and
      short photoperiods suggests a role for floral genes in dormancy transitioning.
AB  - Daylength is an important environmental cue for synchronizing growth, flowering,
      and dormancy with seasonality. As many floral development genes are photoperiod
      regulated, it has been suggested that they could have a regulatory role in bud
      endodormancy. Therefore, the influence of photoperiod was studied on
      inflorescence primordia differentiation and floral pathway related gene
      expression during the development of overwintering buds in Vitis riparia and V.
      spp. 'Seyval'. Photoperiod treatments were imposed 35 days after budbreak, and
      histological and transcriptomic analyses were conducted during the subsequent 42
      days of bud development. Long day (LD, 15 h) and short day (SD, 13 h) buds were
      floral competent by 21 days of photoperiod treatment (56 days after budbreak);
      however, the floral meristem developed faster in LD than in SD buds. Analysis of
      132 floral pathway related genes represented on the Affymetrix Grape Genome array
      indicated 60 were significantly differentially expressed between photoperiod
      treatments. Genes predominantly related to floral transition or floral meristem
      development were identified by their association with distinct grape floral
      meristem development and an expression pattern in LD consistent with their
      previously identified roles in flowering literature. Genes with a potential dual
      role in floral development and dormancy transitioning were identified using
      photoperiod induced differences in floral development between LD and SD buds and
      uncharacteristic gene expression trends in relation to floral development.
      Candidate genes with the potential to play a dual role in SD dormancy induction
      include circadian rhythm or flowering transition related genes: AP2, BT1, COL-13,
      EIN3, ELF4, DDTR, GAI and HY5.

PMID- 20151316
TI  - Dietary fat alters pulmonary metastasis of mammary cancers through cancer
      autonomous and non-autonomous changes in gene expression.
AB  - Metastasis virulence, a significant contributor to breast cancer prognosis, is
      influenced by environmental factors like diet. We previously demonstrated in an
      F2 mouse population generated from a cross between the M16i polygenic obese and
      MMTV-PyMT mammary cancer models that high fat diet (HFD) decreases mammary cancer
      latency and increases pulmonary metastases compared to a matched control diet
      (MCD). Genetic analysis detected eight modifier loci for pulmonary metastasis,
      and diet significantly interacted with all eight loci. Here, gene expression
      microarray analysis was performed on mammary cancers from these mice. Despite the
      substantial dietary impact on metastasis and its interaction with metastasis
      modifiers, HFD significantly altered the expression of only five genes in mammary
      tumors; four of which, including serum amyloid A (Saa), are downstream of the
      tumor suppressor PTEN. Conversely, HFD altered the expression of 211 hepatic
      genes in a set of tumor free F2 control mice. Independent of diet, pulmonary
      metastasis virulence correlates with mammary tumor expression of genes involved
      in endocrine cancers, inflammation, angiogenesis, and invasion. The most
      significant virulence-associated network harbored genes also found in human
      adipose or mammary tissue, and contained upregulated Vegfa as a central node.
      Additionally, expression of Btn1a1, a gene physically located near a putative cis
      acting eQTL on chromosome 13 and one of the metastasis modifiers, correlates with
      metastasis virulence. These data support the existence of diet-dependent and
      independent cancer modifier networks underlying differential susceptibility to
      mammary cancer metastasis and suggest that diet influences cancer metastasis
      virulence through tumor autonomous and non-autonomous mechanisms.

PMID- 20151318
TI  - Caring for the caregivers: an investigation of factors related to well-being
      among parents caring for a child with Smith-Magenis syndrome.
AB  - Smith-Magenis syndrome (SMS) is a complex disorder characterized by numerous
      challenges, including intellectual disability, speech delay, decreased pain
      sensitivity, sleep disturbances, hyperactivity, mood instability, and self
      injury. Caregivers must readily adapt to the ever-changing needs of the child.
      Due to these demands, caregivers may encounter difficulties maintaining their own
      level of well-being. Thus, a total of 112 primary caregivers (i.e., parents) of
      individuals diagnosed with SMS responded to online questionnaires to assess
      demographic and psychosocial factors, such as perceptions of child health
      vulnerability, benefit finding, sleep behaviors, anxiety and depression
      symptomatology, and caregiver satisfaction and self-efficacy, which may be
      related to caregiver well-being. Results show that, among mothers, caregiver well
      being was directly related to perceived child health vulnerability, caregiver
      satisfaction, and benefit finding, and a significant moderating effect was
      observed for depression/anxiety counseling after beginning the caregiver role on
      the relationship between anxiety symptomatology and caregiver well-being. Results
      further suggest that maternal caregivers who report high levels of anxiety but do
      not seek counseling fair the worst in terms of well-being. Among fathers, lower
      depression symptoms and greater benefit finding were related to higher levels of
      caregiver well-being. These data show that many factors play roles in influencing
      coping and well-being among SMS caregivers. Investigating these variables and
      relationships may reveal additional resources and interventions to assist primary
      caregivers.

PMID- 20151317
TI  - Interest and beliefs about BRCA genetic counseling among at-risk Latinas in New
      York City.
AB  - BACKGROUND: Latinas are less likely to use genetic services (counseling and
      testing) for hereditary breast and/or ovarian cancer risk compared to other
      ethnic groups. Meanwhile, little is known about barriers to genetic counseling
      among Latinas at increased risk of inherited breast cancer. METHODS: A two-phase
      pilot study was conducted to examine interest, barriers and beliefs about BRCA
      genetic counseling among at-risk Latinas in New York City and explore the
      potential for developing a culturally-tailored narrative educational tool for use
      in future studies. Phase 1 included quantitative telephone interviews (N = 15)
      with bilingual participants with a personal diagnosis at a young age and/or
      family history of breast and/or ovarian cancer. Quantitative results informed
      development of a narrative prototype educational presentation viewed by a subset
      of participants (N = 10) in Phase 2 focus groups. RESULTS: Despite barriers,
      including lack of awareness/knowledge, concerns related to learning cancer risks
      of family members, and concerns about cost/health insurance, participants
      reported positive attitudes, beliefs and interest in learning about BRCA genetic
      counseling. Further, significant increases in knowledge were demonstrated from
      pre-post presentation (p = 0.04). CONCLUSION: There is an unmet need to educate
      at-risk Latinas about BRCA genetic counseling. Culturally-tailored educational
      materials including narratives may increase knowledge about BRCA genetic
      counseling among this underserved group. The effectiveness of these approaches
      should be tested in future research with larger samples.

PMID- 20151320
TI  - The association between HSD17B1 Ser312Gly polymorphism and breast cancer risk: a
      meta-analysis including 31,053 subjects.
AB  - There are increasing evidences that HSD17B1 plays a significant role in the
      development of breast cancer. However, published data on the association between
      HSD17B1 Ser312Gly polymorphism and breast cancer risk are inconclusive. In order
      to derive a more precise estimation of this relationship, a meta-analysis
      including 9 studies with 31,053 subjects was performed in this study. Crude ORs
      with 95% CIs were used to assess the strength of association between HSD17B1
      Ser312Gly polymorphism and breast cancer risk. The pooled ORs were performed for
      codominant model (Gly/Gly versus Ser/Ser, Gly/Ser versus Ser/Ser), dominant model
      (Gly/Gly + Gly/Ser versus Ser/Ser), and recessive model (Gly/Gly versus Gly/Ser +
      Ser/Ser), respectively. Overall, no significant associations were detected
      between HSD17B1 Ser312Gly polymorphism and breast cancer susceptibility. However,
      in the stratified analysis by ethnicity, significant associations were observed
      in Caucasians for Gly/Gly versus Ser/Ser (OR = 0.91; 95% CI 0.83-1.00), Gly/Ser
      versus Ser/Ser (OR = 0.92; 95% CI 0.85-0.99), and Gly/Gly + Gly/Ser versus
      Ser/Ser (OR = 0.92; 95% CI 0.86-0.98). In conclusion, this study suggests that
      HSD17B1 312Gly allele may be a protective factor for breast cancer development in
      Caucasians. However, large sample and representative population-based studies
      with homogeneous breast cancer patients and well-matched controls are warranted
      to confirm this finding.

PMID- 20151319
TI  - Increased estrogen sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type
      1(17beta-HSD1) following neoadjuvant aromatase inhibitor therapy in breast cancer
      patients.
AB  - Aromatase inhibitors (AIs) are considered the gold standard for endocrine therapy
      of estrogen receptor (ER) positive postmenopausal breast cancer patients. The
      therapy may enhance therapeutic response and stabilize disease but resistance and
      disease progression inevitably occur in the patients. These are considered at
      least partly due to an emergence of alternative intratumoral estrogen production
      pathways. Therefore, in this study we evaluated effects of exemestane (EXE) upon
      the enzymes involved in intratumoral estrogen production including estrogen
      sulfatase (STS), 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), and
      estrogen sulfotransferase (EST) and correlated the findings with therapeutic
      responses including Ki67 labeling index (Ki67). 116 postmenopausal patients with
      invasive ductal carcinoma, stage II/IIIa, were enrolled in JFMC34-0601 clinical
      trials between March, 2006 and January, 2008. EXE of 25 mg/day was administered
      according to the protocol. Pre- and posttreatment specimens of 49 cases were
      available for this study. Status of STS, EST, 17beta-HSD1, ER, progesterone
      receptor (PgR), human epidermal growth factor receptor type 2 (Her2), and Ki67 in
      pre- and post-specimens were evaluated. Specimens examined before the therapy
      demonstrated following features; ER+ (100%), PgR+ (85.7%), and Her2+ (77.6%).
      After treatment, the number of Ki67, PgR, and ER positive carcinoma cells
      demonstrated significant decrement in clinical response (CliR) and pathological
      response (PaR) groups. Significant increment of 17beta-HSD1 and STS
      immunoreactivity was detected in all groups examined except for STS in PaR. EST
      showed significant increment in nonresponsive groups. Alterations of Ki67 of
      carcinoma cells before and after therapy were subclassified into three groups
      according to its degrees. Significant alterations of intratumoral enzymes,
      especially 17beta-HSD1 and STS, were correlated with Ki67 reduction after
      neoadjuvant EXE therapy. This is the first study demonstrating significant
      increment of STS and 17beta-HSD1 following AI neoadjuvant therapy of
      postmenopausal ER positive breast carcinoma patients. This increment may
      represent the compensatory response of breast carcinoma tissues to estrogen
      depletion.

PMID- 20151321
TI  - Sustained lower rates of breast cancer incidence in France in 2007.

PMID- 20151322
TI  - Comparative disease pattern of a patient with a novel BRCA2 truncation and
      knockout models for BRCA2.
AB  - We report a novel germline 490delCT mutation in BRCA2 gene, detected in a 38-year
      old woman with breast cancer. The mutation originates a premature stop at codon
      99, leading to a truncated protein, and has not been documented in any published
      report to the best of our knowledge.

PMID- 20151323
TI  - Resistance against various fungal pathogens and reniform nematode in transgenic
      cotton plants expressing Arabidopsis NPR1.
AB  - Cotton is an economically important crop worldwide that suffers severe losses due
      to a wide range of fungal/bacterial pathogens and nematodes. Given its
      susceptibility to various pathogens, it is important to obtain a broad-spectrum
      resistance in cotton. Resistance to several fungal and bacterial diseases has
      been obtained by overexpressing the Non-expressor of Pathogenesis-Related genes-1
      (NPR1) in various plant species with apparently minimal or no pleiotropic
      effects. We examined the efficacy of this approach in cotton by constitutive
      expression of the Arabidopsis (Arabidopsis thaliana) NPR1 gene. The results show
      that NPR1-expressing lines exhibited significant resistance to Verticillium
      dahliae isolate TS2, Fusarium oxysporum f. sp. vasinfectum, Rhizoctonia solani,
      and Alternaria alternata. Interestingly, the transformants also showed
      significant resistance to reniform nematodes. Analysis of defense-related,
      biochemical and molecular responses suggest that when challenged with pathogens
      or certain systemic acquired resistance-inducing chemicals, the transgenic lines
      respond to a greater degree compared to the wild-type plants. Importantly, the
      basal activities of the defense-related genes and enzymes in uninduced
      transformants were no different than those in their non-transgenic counterparts.
      The results provide additional evidence supporting the role of NPR1 as an
      important part of the plant defense system and suggest a means to achieve broad
      spectrum resistance to pathogens via genetic engineering.

PMID- 20151324
TI  - "It's medically proven!": Assessing the dissemination of religion and health
      research.
AB  - The recent proliferation of research on the connection between religion and
      health has raised concerns among some scholars about how these studies affect
      people's understanding of that connection. However, such concerns assume that
      religion and health research reaches religious audiences and informs their
      understanding of the connection between religion and health. We explore the
      veracity of these assumptions, asking two questions: (1) Is religion and health
      research disseminating into the American public? (2) Do religious persons
      incorporate religion and health research into their understanding of the
      connection between religion and health? We conduct two studies to answer these
      questions. First, we search three newspapers (The New York Times, The Los Angeles
      Times, and The Atlanta Journal-Constitution) and three news magazines (Newsweek,
      Time, and U. S. News and World Report) for articles that mention religion and
      health research. In the second study, we analyze interview transcripts for
      respondents' mentions of religion and health research when discussing the
      relationship between religion and health. Our results indicate substantial growth
      over time in media reporting on religion and health research but reveal that only
      a limited portion of religious persons cite such research in explaining their
      conceptualizations of the connection between religion and health.

PMID- 20151325
TI  - Leucine promotes leptin receptor expression in mouse C2C12 myotubes through the
      mTOR pathway.
AB  - Leptin plays a critical role in regulating muscle protein metabolism by binding
      with leptin receptors in a 1:1 stoichiometry. However, the role for leucine in
      the regulation of leptin receptor expression in muscle has not been investigated.
      The present study was conducted to test the hypothesis that leucine regulates
      leptin receptor levels in C2C12 myotubes. Cells were cultured in the presence of
      DMEM/F12 medium containing supplemental 0 or 5 mM L: -leucine. Leptin receptor
      expression by C2C12 myotubes peaked at 2 h post-supplementation. Additionally,
      leucine stimulated leptin receptor expression at both mRNA and protein levels in
      a dose-dependent manner. Furthermore, leucine enhanced the phosphorylation of
      mammalian target of rapamycin (mTOR). Addition of rapamycin (an inhibitor of
      mTOR) to culture medium completely suppressed leucine-induced activation of mTOR
      and inhibited leucine-stimulated leptin receptor production. These results
      indicate that leucine affects leptin receptor expression in muscle cells via the
      mTOR signaling pathway.

PMID- 20151326
TI  - Characterization and expression analysis of KAP7.1, KAP8.2 gene in Liaoning new
      breeding cashmere goat hair follicle.
AB  - Keratin-associated protein is one of the major structural proteins of the hair,
      whose content in hair has important effect on the quality of cashmere. In order
      to study the relationship between HGTKAP gene expression and cashmere fineness,
      the quantitative real-time RT-PCR (qRT-PCR) was firstly used to detect the levels
      of KAP7.1, KAP8.2 gene expression in the primary and secondary hair follicles;
      semi-quantitative RT-PCR was used to detect whether KAP7.1, KAP8.2 gene are
      expressed in heart, liver, spleen, lung, kidney tissues; and in situ
      hybridization(ISH) to detect KAP7.1 gene expression location. qRT-PCR result
      showed that the expression of both KAP7.1 and KAP8.2 gene in the secondary hair
      follicles are significantly higher than that in the primary follicles, relative
      quantitative analysis obtained that KAP7.1 was 2.28 times, while KAP8.2 was 2.71
      times. Semi-quantitative RT-PCR results revealed that KAP 7.1 and KAP8.2 mRNA
      were not detected in the heart, liver, spleen, lung and kidney tissues,
      demonstrating that KAP7.1 and KAP8.2 were specially expressed in hair follicles,
      participating in hair formation. Moreover, KAP7.1 gene has a strong expression in
      the cortical layer, inner root sheath of the primary follicles and the cortical
      layer, inner root sheath and hair matrix of the secondary hair follicles by ISH
      analysis. Taken together, the evidence presented here indicated that in the
      formation of cashmere and wool, differential expression of these two genes in the
      primary and secondary hair follicles may have an important role in regulating the
      fiber diameter.

PMID- 20151327
TI  - Principles of medical care for children with attention deficit hyperactivity
      disorder.

PMID- 20151328
TI  - Non-pharmacological correction of impaired microcirculation in children with
      diabetic polyneuropathy.
AB  - A total of 25 boys and 20 girls aged 5-17 years with type I diabetes mellitus and
      disease durations of 2-10 years were studied. All had diabetic polyneuropathy.
      The microcirculation was studied by laser Doppler flowmetry. Treatment consisted
      of using a running impulse magnetic field. This method was found to be effective
      in diabetic polyneuropathy with the running field along the limb towards the
      periphery at a run velocity (field modulation frequency) being a multiple of the
      nerve fiber spike conduction velocity.

PMID- 20151329
TI  - Dynamics of cognitive anomalies in patients with first episodes of juvenile
      endogenous psychosis.
AB  - The therapeutic dynamics of neuropsychological and neurophysiological markers of
      impairments to cognitive functions were studied in groups of patients with first
      episodes of juvenile endogenous psychosis (90 patients). At the initial stage of
      remission, subjects were found to show improvements in processes associated with
      voluntary regulation of cognitive functions (due to the activity of extensive
      networks of cortical and subcortical structures), while more automatic processes
      (associated mainly with the temporal areas of the brain) remained abnormal.
      Changes in neurocognitive anomalies during the onset of remission were also
      identified in groups of patients in whom episodes had different syndromal
      structures - catatonic, hallucinatory-delusional, and affective-delusional.

PMID- 20151330
TI  - Involvement of the NO synthase system in stress-mediated brain reactions.
AB  - The neurosis-like state developing as a result of chronic stress in animals and
      accompanied by transient cerebral hypoxia can lead to significant impairments to
      many brain structures. The effects of the humoral components of the stress
      reaction on the brain are mediated by both extra- and intracellular signal
      pathways, among which nitric oxide (NO) is of great importance. We report here
      immunohistochemical studies of the expression of the constitutive neuronal (nNOS)
      and inducible (iNOS) isoforms of NO synthase in neurons in the brains of white
      rats in conditions of chronic stress leading to the development of a neurosis-
      like state. Chronic stress was found to induce increases in nNOS and iNOS
      expression in many parts of the brain, predominantly in the neocortex and
      hippocampus. Administration of the nonspecific NOS inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME) (10 mg/kg) led to increases in the animals'
      depression, which was accompanied by reductions in motor and investigative
      activity assessed using traditional tests. This NOS inhibitor produced a minor
      increase in the expression of iNOS only. Thus, NO was shown to be involved in
      mediating the effects of stress with development of a neurosis-like state.

PMID- 20151332
TI  - MRI morphometry of the cerebral ventricles in patients with attention deficit
      hyperactivity disorder.
AB  - A total of 27 right-handed patients aged 7-30 years with diagnoses of attention
      deficit hyperactivity disorder were studied using standard MRI scans. Of these,
      14 were aged below 13 years. The volumes of the lateral ventricles were measured
      using T1-weighted MRI images of sagittal sections of the brain to a precision of
      3 mm3. External head sizes were also measured to allow ventricle volumes to be
      normalized. All patients underwent complex neuropsychological investigations.
      Memory was assessed, along with visual, auditory, tactile, and spatial
      recognition functions and the motor and speech spheres. Test data were assessed
      in terms of the severity of impairments associated with one brain structure or
      another on a tenpoint scale. Assessment points were summed for each hemisphere,
      for the "first area" (cortical structures), and all structures for statistical
      analysis. Neuropsychological testing revealed functional impairments
      predominantly of the frontal areas of the hemispheres, the hippocampus, and the
      reticular formation. Neuropsychological deficits were least linked with
      alterations in the postcentral and parietal areas of the cortex. Statistical
      analysis demonstrated a significant positive correlation between the normalized
      left lateral ventricle volume and the degree of neuropsychological impairments (r
      = 0.5127 at p = 0.0063) for the whole study group. The correlation was more
      marked on comparison of the normalized left ventricular volume and the severity
      of neuropsychological impairments related to the left hemisphere (r = 0.6303 at p
      = 0.0004). A relationship was seen between the volume of the intraventricular
      space and cortical functional impairments (r = 0.5071 at p = 0.0069) in patients
      less than 13 years old. A relationship between ventricular volume and linear head
      size was confirmed (r = 0.5759 at p = 0.0017), which was more marked in subjects
      less than 13 years old (r = 0.6833 at p = 0.01).

PMID- 20151331
TI  - Return of excitatory waves from field CA1 to the hippocampal formation is
      facilitated after tetanization of Schaffer collaterals during sleep.
AB  - Current concepts hold that during learning in waking animals, new information is
      transmitted from the neocortex to the hippocampus, where it leaves a temporary
      trace in the form of a mosaic of modified synapses. During sleep, reactivation of
      the neuron population initially activated by the new stimulus has the result that
      this information is returned to the neocortex, ensuring consolidation of a
      permanent memory trace. Exchange of information between the neocortex and
      hippocampal formation is mediated mainly by the entorhinal cortex, whose internal
      connections, in principle, allow "messages" from the output of the hippocampal
      formation to return to its inputs. Our experiments in awake and sleeping rabbits
      demonstrated that waves of excitation can return to hippocampal field CA1 and the
      dentate gyrus via fibers of the perforant path, these waves having initially
      entered field CA1 via potentiated synapses of Schaffer collaterals; during sleep,
      re-entrant waves of excitation reach a maximum and have a high probability of
      evoking discharges of dentate gyrus neurons. Thus, the new stimulus, potentiating
      synaptic connections in the hippocampus and, probably, the entorhinal cortex
      during waking, create conditions for reactivation of the corresponding
      hippocampal neuron populations during sleep by waves of excitation returning via
      the entorhinal cortex.

PMID- 20151333
TI  - Quantitative differences in intervertebral disc-matrix composition with age
      related degeneration.
AB  - This study was carried out to determine the effect of age on the intervertebral
      disc, using a rabbit model. Anulus fibrosus and nucleus pulposus tissue from New
      Zealand white rabbits aged 3 years old (old rabbits) and 6 months old (young
      rabbits) were used. The water content, the proteoglycan, the DNA content, and the
      mRNA levels of aggrecan, type I collagen, and type II collagen were all measured
      for each sample. Water, proteoglycan, DNA, and the mRNA levels of aggrecan and
      type II collagen were all greater in the nucleus pulposus of the young rabbits as
      compared to the old. For the anulus fibrosus, the difference between young and
      old is less marked with only proteoglycan and DNA being greater in the young disc
      as compared to the old. Clearly, according to our results, it is the nucleus
      pulposus that suffers the brunt of the changes with age.

PMID- 20151334
TI  - Free tissue transfer versus pedicled flap reconstruction of head and neck
      malignancy defects.
AB  - BACKGROUND: With the advent of microsurgery the pedicled flap is considered by
      many to be an outdated surgical option. AIMS: To explore the relationship between
      flap survival and pre-morbid risk factors, conduct a comparative analysis of flap
      and systemic morbidities and complete a cosmesis and functionality assessment for
      oral and oropharyngeal reconstruction patients. METHODS: 114 patients, over a 13
      year period, who had a one-stage reconstructive procedure employing the
      pectoralis major myocutaneous flap (PMMF) or radial forearm-free flap (RFFF).
      RESULTS: Variables, including age, smoking and radiation exposure were not
      statistically significant predictors of flap survival probability. Atelectasis
      was a significant post-op finding of RFFF patients. Flap dehiscence of >50% was a
      significant morbidity of PMMF. No statistical difference in cosmetic deformity,
      diet and socialisation was noted. CONCLUSIONS: Pectoralis major myocutaneous flap
      remains an enduring and safe flap; however, the RFFF has markedly improved speech
      performance over the PMMF.

PMID- 20151335
TI  - Slippery platelet syndromes in subdural hematoma.
AB  - BACKGROUND: This study investigates platelet dysfunction in patients with
      subdural hematomas (SDH) using platelet function analysis (PFA). METHODS: PFA
      using the PFA-100 (Dade International Inc., Miami, FL) was performed at admission
      using the collagen-epinephrine and collagen-ADP assays in 58 SDH patients.
      Clinical and radiologic information was collected. RESULTS: Normal PFA results
      were present in 36 patients (62%; PFA collagen:epinephrine assay (s) 118 ave; PFA
      collagen:adenosine diphosphate assay (s) ave 75) and abnormal platelet function
      in 22 patients (38%; PFA collagen:epinephrine assay (s) 231 average; PFA
      collagen:adenosine diphosphate assay (s) 124 average). Compared to patients with
      normal PFA results, patients with abnormal PFA results were more likely to have
      hypertension (22 vs. 55%; P = 0.01), take clopidogrel (3 vs. 32%; P = 0.001), and
      use anti-platelet medications and non-steroidal anti-inflammatory agents (22 vs.
      59%; P = 0.004). Measurements of baseline CT for midline shift, maximum
      thickness, presence of blood/fluid levels in the hematoma, and presence of
      additional sites of intracranial bleeding did not reveal significant differences
      based on PFA testing. Platelet dysfunction improved after platelet transfusions
      (PFA collagen:epinephrine assay: baseline 270 s, CI 61 s; after transfusion 124
      s, CI 50 s, P < 0.001). CONCLUSION: Platelet dysfunction was found in 38% of SDH
      patients. This finding adds to our understanding of the pathophysiology of SDH.
      Since platelet transfusions are indicated for platelet dysfunction accompanied by
      major bleeding or need for surgery, these results impact peri-operative
      management.

PMID- 20151336
TI  - Stability of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in combination.
AB  - In vivo, the DNA methyltransferase inhibitor, 5-fluoro-2'-deoxycytidine (FdCyd,
      NSC-48006), is rapidly converted to its unwanted metabolites. Tetrahydrouridine
      (THU, NSC-112907), a cytidine deaminase inhibitor can block the first metabolic
      step in FdCyd catabolism. Clinical studies have shown that co-administration with
      THU can inhibit the metabolism of FdCyd. The National Cancer Institute is
      particularly interested in a 1:5 FdCyd/THU formulation. The purpose of this study
      was to investigate the in vitro pH stability of FdCyd and THU individually and in
      combination. A stability-indicating high-performance liquid chromatography method
      for the quantification of both compounds and their degradants was developed using
      a ZIC(R)-HILIC column. The effect of THU and FdCyd on the in vitro degradation of
      each other was studied as a function of pH from 1.0 to 7.4 in aqueous solutions
      at 37 degrees C. The degradation of FdCyd appears to be first-order and acid
      catalyzed. THU equilibrates with at least one of its degradants. The combination
      of FdCyd and THU in solution does not affect the stability of either compound.
      The stability and compatibility of FdCyd and THU in the solid state at increased
      relative humidity and at various temperatures are also evaluated.

PMID- 20151337
TI  - Ciprofloxacin as ocular liposomal hydrogel.
AB  - The purpose of this study was to prepare and characterize an ocular effective
      prolonged-release liposomal hydrogel formulation containing ciprofloxacin.
      Reverse-phase evaporation was used for preparation of liposomes consisting of
      soybean phosphatidylcholine (PC) and cholesterol (CH). The effect of PC/CH molar
      ratio on the percentage drug encapsulation was investigated. The effect of
      additives such as stearylamine (SA) or dicetyl phosphate (DP) as positive and
      negative charge inducers, respectively, were studied. Morphology, mean size,
      encapsulation efficiency, and in vitro release of ciprofloxacin from liposomes
      were evaluated. For hydrogel preparation, Carbopol 940 was applied. In vitro
      transcorneal permeation through excised albino rabbit cornea was also determined.
      Optimal encapsulation efficiency of 73.04 +/- 3.06% was obtained from liposomes
      formulated with PC/CH at molar ratio of 5:3 and by increasing CH content above
      this limit, the encapsulation decreased. Positively charged liposomes showed
      superior entrapment efficiency (82.01 +/- 0.52) over the negatively charged and
      the neutral liposomes. Hydrogel containing liposomes with lipid content PC, CH,
      and SA in molar ratio 5:3:1, respectively, showed the best release and
      transcorneal permeation with the percentage permeation of 30.6%. These results
      suggest that the degree of encapsulation of ciprofloxacin into liposomes and
      prolonged in vitro release depend on composition of the vesicles. In addition,
      the polymer hydrogel used in preparation ensure steady and prolonged transcorneal
      permeation. In conclusion, ciprofloxacin liposomal hydrogel is a suitable
      delivery system for improving the ocular bioavailability of ciprofloxacin.

PMID- 20151338
TI  - Cuff inflation as an aid to nasotracheal intubation using the Airtraq
      laryngoscope.

PMID- 20151339
TI  - The "jaw thrust" maneuver rather than the "BURP" maneuver improves the glottic
      view for Pentax-AWS assisted tracheal intubation in a patient with a laryngeal
      aperture.

PMID- 20151340
TI  - Hydroxyethyl starch 130/0.4 attenuates early hepatic damage in
      ischemia/reperfusion injury.
AB  - PURPOSE: Ischemia/reperfusion injury (IRI) remains a clinical challenge. We
      tested the hypothesis that fluid therapy using hydroxyethyl starch (HES) 130/0.4
      during the early phase of IRI in rat liver decreases markers of hepatic injury.
      METHODS: We induced liver IRI in three groups of rats anesthetized with ketamine
      and chlorpromazine by means of 60 min of segmental hepatic ischemia followed by
      120 min of reperfusion. At the onset of reperfusion, Group 1 (IRI + HES; n = 12)
      was given 13 mL.kg(-1) of HES; Group 2 (IRI + HS; n = 12) received the same
      volume of 7.5% saline (HS), and Group 3 (IRI-only; n = 12) received no fluid.
      Three other groups of 12 animals each were sham-operated and received the same
      fluid as the test groups. We euthanized the animals after three hours, drew blood
      for alanine aminotransferase (ALT) quantification, and took ischemic liver
      samples for histomorphological study. RESULTS: Serum ALT activity was greater in
      all of the IRI groups than in the sham-operated animals. The ALT activity was
      1,081 +/- 575 IU.L(-1) in IRI + HES Group 1; 2,363 +/- 1,839 IU.L(-1) in IRI + HS
      Group 2; and 2,866 +/- 2,491 IU.L(-1) in IRI-only Group 3. There was a
      statistically significant difference between the IRI + HES and the IRI-only
      groups (P = 0.001), but not between the IRI + HS and the IRI-only groups (P >
      0.05). Likewise, histological scores were greater in all IRI groups compared with
      the sham-operated animals. Scores were higher in the IRI-only group (median 3.5)
      than in the groups receiving fluid (IRI + HES median 2; IRI + HS median 3). The
      difference between IRI + HES and IRI-only was statistically significant (P =
      0.008) but not so between IRI + HS and IRI-only (P > 0.05). CONCLUSIONS: Giving
      HES 130/0.4 attenuates rat liver IRI compared with no fluid, while giving HS does
      not. This suggests a role for HES in hepatoprotection associated with liver IRI.

PMID- 20151342
TI  - Local anesthetic systemic toxicity.
AB  - PURPOSE: The practice of regional anesthesia has been revitalized of late with
      the popularization of ultrasound-guided techniques. Advocates must be vigilant
      for the effects of unintentionally high blood levels of local anesthetic.
      Systemic local anesthetic toxicity, though rare, is a potentially devastating
      occurrence. This narrative review summarizes the effects of local anesthetic
      toxicity. We highlight how these toxic effects have motivated the search for a
      safe and long-acting local anesthetic. We outline current prevention and
      treatment options and appraise an emerging therapy in light of unfolding
      evidence. SOURCES: A search of the English language literature was conducted
      using the PubMed database from the National Library of Medicine. Bibliographies
      of retrieved articles were used to retrieve additional articles. PRINCIPAL
      FINDINGS: The advent of multiple safety steps has led to a dramatic reduction in
      the incidence of local anesthetic toxicity over the past 30 years. Rising plasma
      levels of local anesthetic lead to a progressive spectrum of neurological and
      cardiac effects. Seizure activity may herald the onset of myocardial depression
      and ventricular arrhythmias that are often refractory to treatment. In addition
      to specific measures, such as lipid emulsion therapy, general supportive measures
      are warranted, for example, Advanced Life Support Guidelines. CONCLUSION:
      Vigilance during the performance of regional anesthesia and immediate
      intervention at the earliest sign of toxicity improve the chances of successful
      treatment.

PMID- 20151341
TI  - Topical lidocaine improves conditions for laryngeal mask airway insertion.
AB  - PURPOSE: We hypothesized that optimal laryngeal mask airway (LMA) insertion
      conditions might be achieved with topical lidocaine and a smaller dose of
      propofol. In this study, insertion conditions after topical lidocaine 40 mg
      followed by propofol 2 mg.kg(-1) were compared with propofol 2 mg.kg(-1) or
      propofol 3 mg.kg(-1) alone. METHODS: Ninety patients were recruited for this
      randomized prospective double-blind study. One group received four sprays of
      topical lidocaine (40 mg) over the posterior pharyngeal wall followed by propofol
      2 mg.kg(-1) (Group 2PL; n = 30). The other two groups received four sprays of
      0.9% normal saline followed by propofol 2 mg.kg(-1) (Group 2P; n = 30) or by
      propofol 3 mg.kg(-1) (Group 3P; n = 30). The frequency of optimal insertion
      conditions (successful insertion at the first attempt without adverse responses)
      and side effects were recorded. RESULTS: The frequency of optimal insertion
      conditions was greater in Group 2PL (20/30, 67%) and Group 3P (22/30, 73%) than
      in Group 2P (11/20, 37%) (P = 0.009). In Group 3P, the mean blood pressure was
      lower than in the other groups prior to LMA-Classic insertion (P = 0.003) but was
      similar after insertion. The incidence of apnea was greater in Group 3P patients
      (17/30, 57%) than in Group 2P (2/30, 7%) or Group 2PL patients (1/30, 3%) (P <
      0.001). CONCLUSION: Topical lidocaine 40 mg followed by propofol 2 mg.kg(-1) can
      provide optimal insertion conditions of the LMA-Classic comparable to those of
      propofol 3 mg.kg(-1), with fewer hemodynamic changes and a lower incidence of
      apnea.

PMID- 20151343
TI  - [Dyspnea in palliative medicine].

PMID- 20151344
TI  - [Nasal application of fentanyl citrate as symptom control against breathlessness
      in palliative care--overview and case report].
AB  - Severe dyspnoea is the most threatening symptom of the dying and one of the main
      reasons for undesirable hospitalisation in end of life. Especially in home care
      there is a need for a noninvasive, safe and highly effective method for symptom
      control. Fentanyl is an appropriate drug because of its fast onset and short
      duration of action. Since 2003 medicated the Palliative Net Easthessia (PNO) more
      than 600 home care patients with nasal Fentanyl (naF). The method is simple and
      the user should bear in mind that the substance is highly effective. Both
      physician and pharmacist should inform themselves adequately before the first use
      about the basics of the manufacturing and use. Two typical case reports will be
      shown. Clinical experience let us assume that intranasal administration against
      dyspnoea is not inferior to the intravenous symptom control. In ambulant care
      caused by the use of the caring relatives or the patients themselves non
      invasivity is a great advantage. Prospective studies are in need to prove the
      method.

PMID- 20151345
TI  - Pathophysiology and diagnosis of dyspnea in patients with advanced cancer.
AB  - The reported prevalence of dyspnea in patients with various cancers ranges from
      19% to 64%. For optimal clinical management of dyspnea in cancer patients,
      accurate diagnosis of the underlying cause and thorough understanding of the
      pathomechanisms of dyspnea seems mandatory. The clinical approach to a patient
      with advanced cancer and dyspnea should include adequate history taking, physical
      examination, and selected diagnostic investigations. These should be performed
      immediately to enable quick treatment decisions. In addition, self assessment of
      the intensity of dyspnea by the patient may help to assess patient's needs as
      soon as possible.

PMID- 20151346
TI  - Opioids for symptomatic therapy of dyspnoea in patients with advanced chronic
      heart failure--is there evidence?
AB  - In times of reduced mortality from myocardial infarction and ageing of the
      population, the number of patients suffering from chronic heart failure continues
      to rise. In spite of optimal cardiological treatment, many patients suffer from
      dyspnoea. The use of commonly used drugs in palliative care such as opioids for
      the relief of dyspnoea is uncommon in this group of patients. We conducted a
      limited systematic literature research in order to find out if there is evidence
      for the use of any systemic pharmacological substance for the symptomatic relief
      of dyspnoea in chronic heart failure patients. Three randomised controlled trials
      with opioids could be identified. The quality of the identified studies does not
      support the avoidance of the use of opioids in patients with chronic heart
      failure to relieve dyspnoea. But further studies are recommended to support the
      use of opioids in patients with chronic heart failure for relief of
      breathlessness to improve the quality of life of this growing population.

PMID- 20151347
TI  - Management of dyspnea in patients with chronic obstructive pulmonary disease.
AB  - A progressive and debilitating illness, chronic obstructive pulmonary disease
      (COPD) has major worldwide impact. In addition to the care for underlying causes
      of disease, COPD treatment involves palliative intervention to address associated
      symptoms; in later stages of disease, when the underlying disease has been
      maximally treated, symptom management assumes primacy as the goal of care.
      Dyspnea is the most distressing symptom experienced by COPD patients. When
      dyspnea cannot be relieved by traditional COPD management strategies (i.e.,
      "refractory dyspnea"), the goal of care shifts from prolonged survival to
      minimized symptoms, improved function, and enhanced quality of life. Numerous
      pharmacologic and non-pharmacologic interventions are available to achieve these
      goals, but supporting evidence is variable. This review summarizes options for
      managing refractory dyspnea in COPD patients, referring to the available evidence
      and highlighting areas for further investigation. Topics include oxygen, opioids,
      psychotropic drugs, inhaled frusemide, Heliox28, nutrition, psychosocial support,
      and breathing techniques.

PMID- 20151348
TI  - Management of refractory breathlessness in patients with advanced cancer.
AB  - Breathlessness is a common and distressing symptom in advanced cancer. Management
      comprises non-pharmacological and pharmacological interventions, which are best
      combined. There is some evidence mainly derived from COPD studies for walking
      aids, neuro-muscular electrical stimulation, fan and breathlessness services.
      Opioids are the drugs of choice for pharmacological management of breathlessness.
      There is currently not enough evidence to support the routine use of
      benzodiazepines, other anxiolytics, antidepressants, phenothiazines, inhaled
      furosemide and oxygen.

PMID- 20151349
TI  - [Invasive and non-invasive ventilation in conflict with best palliative care in
      severe COPD].
AB  - This example of an 80-year-old patient with severe lung disease and respiratory
      failure demonstrates the difficult relationship between the patient's needs,
      physical symptoms, and social problems. This man decides after a prolonged and
      difficult in-patient treatment actively for home ventilation rather than die of
      respiratory failure. He opts for tracheostomy and invasive ventilation because he
      cannot handle non-invasive mask-ventilation sufficiently by himself. It requires
      professional communication and support to gain the acceptance of family and
      caregivers for home ventilation. A survey of existing data on end of life
      decision-making in end-stage lung disease is given.

PMID- 20151350
TI  - [BIPAP-mask-ventilation in terminal amyotrophic lateral sclerosis (ALS)].
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, neuromuscular disease
      without any curative therapy at the moment. Non-invasive BIPAP-ventilation has
      proven to be helpful to cope with the increasing hypoventilation due to weakness
      in ventilatory muscles in ALS. If BIPAP-ventilation is well tolerated by the
      patient, it can be very helpful for symptom control in palliative homecare. In
      this case presentation we discuss how non-invasive ventilation can influence
      perception of dying at home and thereby quality of life of patients, caregivers
      and members of palliative teams. We will see that especially during this sensible
      terminal phase various questions and fears concerning the mechanically assisted
      ventilation may arise. These issues should be addressed in advance with careful
      attention and information. Members of palliative teams should therefore be
      provided with good training and regular supervision.

PMID- 20151351
TI  - [The influence of surgical and restorative dental treatment prior to cardiac
      valve surgery on the long-term demand of dental treatment: a prospective clinical
      study].
AB  - The study objective was to evaluate the long-term influence of non-radical
      surgical and restorative dental treatment modalities prior to elective cardiac
      valve replacement on the subsequent dental treatment demand. A total of 305
      patients preceding cardiac valve surgery were screened and the appropriate dental
      treatment was initiated. After 36 months 80 patients were re-evaluated
      clinically, of which 60 required dental restorations of 155 teeth, mostly due to
      periodontal pathology. Independent of the sub-group there was a statistically
      substantial increase of the treatment demand compared to the time of initial
      examination. In addition, at the time of final re-evaluation the definite
      treatment need significantly increased far beyond anticipation, potentially due
      to inadequate dental procedures during the follow-up interval. Irrespective of
      any dental treatment or antibiotic application, endocarditis did not occur in any
      patient. Non-radical dental restoration prior to cardiac valve replacement can
      only be successful, if a standardized dental follow-up with common monitoring
      forms is provided. The risk of prosthetic valve infective endocarditis based on a
      dental focus is probably overestimated.

PMID- 20151352
TI  - [On the lack of young physicians in trauma surgery and orthopaedics].

PMID- 20151353
TI  - [Reconstruction of osteochondral defects with a stem cell-based cartilage-polymer
      construct in a small animal model].
AB  - AIM: Mesenchymal stem cells have a high therapeutic potential for the
      reconstruction of articular cartilage defects. In this study, a cartilage-polymer
      construct using mesenchymal stem cells from trabecular bone and a polylactic acid
      polymer was fabricated with a press-coating technique. We investigated whether
      cells from human trabecular bone fragments have the same chondrogenic
      differentiation potential as mesenchymal stem cells derived from bone marrow and
      whether it is possible to reconstruct an osteochondral lesion in the nude rat
      with the fabricated construct. METHOD: Cells were obtained from the femoral head
      of patients undergoing total hip arthroplasty. The fabrication of the constructs
      was performed by centrifugation of 1.5x10(6) cells to a cell pellet which was
      then placed in a polymer block. The fabricated cell constructs were cultivated
      for 3 weeks in a serum-free medium, supplemented with transforming growth factor
      beta1. Every third day, the chondrogenic differentiation was analysed using
      chondrogenic and osteogenic marker genes. After three weeks the constructs were
      implanted into 5 mm osteochondral defects of the knee joint of nude rats. After 4
      and 12 weeks histochemical and immunohistochemical analyses were performed.
      RESULTS: At the end of the culture period the constructs showed a proteoglycan
      rich extracellular matrix with the expression of collagen types II, IX and X as
      well as aggrecan und COMP (cartilage oligomeric matrix protein). No osteogenic
      markers except collagen type I could be detected. The analysis of the in vivo
      experiment showed a good defect filling with a reconstructed cartilage surface
      along with increasing resorption of the polymer. CONCLUSION: We have shown that
      it is possible to fabricate cartilage-polymer constructs from trabecular bone
      derived cells, and that the cells have the same chondrogenic differentiation
      potential as mesenchymal stem cells derived from bone marrow. With the fabricated
      cartilage-polymer construct it is possible to reconstruct an osteochondral defect
      in the knee joint of the nude rat.

PMID- 20151354
TI  - [Open fracture and soft tissue injury].

PMID- 20151355
TI  - [From molecule to medicine--drug development].

PMID- 20151356
TI  - CT angiography of the renal arteries and veins: normal anatomy and variants.
AB  - Conventional angiography has long been regarded as gold standard imaging modality
      for evaluation of the renal vasculature. Introduction of multidetector computed
      tomography (MDCT) angiography had a groundbreaking impact on evaluation of the
      renal vessels and is gradually replacing conventional angiography as standard
      imaging. Herein, we review and illustrate the normal and variant anatomy of renal
      vessels with special emphasis on imaging protocols and reconstruction techniques
      in MDCT.

PMID- 20151357
TI  - Assessment of vascularity with color Doppler ultrasound in gynecomastia.
AB  - PURPOSE: The aim of this study was to analyze the presence and type of
      vascularity with color Doppler ultrasound (CDUS) in gynecomastia, to describe
      gray-scale ultrasound (US) and CDUS features in different stages of gynecomastia,
      and to compare these findings with the characteristic US appearances of Tanner
      stages. MATERIALS AND METHODS: A total of 108 breasts of 54 males aged 11-27
      years with complaint of gynecomastia and US verification of gynecomastia were
      evaluated. Each breast was then classified according to Tanner stages. The
      retroareolar thickness was measured. The breast was divided into three regions
      (medial, lateral, and retroareolar) and the arterial flow was scored according to
      the number of regions in which arterial flow was observed. Venous blood flow was
      scored according to the number of vessels in each breast. RESULTS: Gynecomastia
      was present in 78 breasts with a retroareolar thickness of 5-31 mm and symptom
      duration of 1-300 weeks. Fifteen breasts with gynecomastia had no arterial or
      venous flow. Tanner stages were found to be strongly associated with arterial and
      venous flow scores, duration of symptoms, and retroareolar thickness (P < 0.001).
      CONCLUSION: This study shows that vascular structures should be accepted as a
      component of gynecomastia. Vascularity in gynecomastia corresponds to progression
      of breast development, and as the process advances vascularity becomes more
      prominent.

PMID- 20151359
TI  - The circadian timing system in the brain of the fifth larval instar of Rhodnius
      prolixus (hemiptera).
AB  - The brain of larval Rhodnius prolixus releases neurohormones with a circadian
      rhythm, indicating that a clock system exists in the larval brain. Larvae also
      possess a circadian locomotor rhythm. The present paper is a detailed analysis of
      the distribution and axonal projections of circadian clock cells in the brain of
      the fifth larval instar. Clock cells are identified as neurons that exhibit
      circadian cycling of both PER and TIM proteins. A group of eight lateral clock
      neurons (LNs) in the proximal optic lobe also contain pigment-dispersing factor
      (PDF) throughout their axons, enabling their detailed projections to be traced.
      LNs project to the accessory medulla and thence laterally toward the compound eye
      and medially into a massive area of arborizations in the anterior protocerebrum.
      Fine branches radiate from this area to most of the protocerebrum. A second group
      of clock cells (dorsal neurons [DNs]), situated in the posterior dorsal
      protocerebrum, are devoid of PDF. The DNs receive two fine axons from the LNs,
      indicating that clock cells throughout the brain are integrated into a timing
      network. Two axons of the LNs cross the midline, presumably coordinating the
      clock networks of left and right sides. The neuroarchitecture of this timing
      system is much more elaborate than any previously described for a larval insect
      and is very similar to those described in adult insects. This is the first report
      that an insect timing system regulates rhythmicity in both the endocrine system
      and behavior, implying extensive functional parallels with the mammalian
      suprachiasmatic nucleus.

PMID- 20151358
TI  - Specializations of gastrin-releasing peptide cells of the mouse suprachiasmatic
      nucleus.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus regulates daily rhythms in
      physiology and behavior. It is composed of a heterogeneous population of cells
      that together form the circuits underlying its master clock function. Numerous
      studies suggest the existence of two regions that have been termed core and
      shell. At a gross level, differences between these regions map to distinct
      functional differences, although the specific role(s) of various peptidergic
      cellular phenotypes remains unknown. In mouse, gastrin-releasing peptide (GRP)
      cells lie in the core, are directly retinorecipient, and lack detectable
      rhythmicity in clock gene expression, raising interest in their role in the SCN.
      Here, we provide evidence that calbindin-expressing cells of perinatal mouse SCN
      express GRP, identified by a green fluorescent protein (GFP+), but lack
      detectable calbindin later in development. To explore the intra-SCN network in
      which GRP neurons participate, individual GFP+ cells were filled with tracer and
      their morphological characteristics, processes, and connections, as well as those
      of their non-GFP-containing immediate neighbors, were compared. The results show
      that GFP+ neurons form a dense network of local circuits within the core,
      revealed by appositions on other GFP+ cells and by the presence of dye-coupled
      cells. Dendrites and axons of GFP+ cells make appositions on arginine vasopressin
      neurons, whereas non-GFP cells have a less extensive fiber network, largely
      confined to the region of GFP+ cells. The results point to specialized circuitry
      within the SCN, presumably supporting synchronization of neural activity and
      reciprocal communication between core and shell regions.

PMID- 20151360
TI  - Basal ganglia and thalamic input from neurons located within the ventral tier
      cell cluster region of the substantia nigra pars compacta in the rat.
AB  - The most caudally located dopaminergic (DA) ventral tier neurons of the
      substantia nigra pars compacta (SNc) form typical cell clusters that are deeply
      embedded in the substantia nigra pars reticulata (SNr). Here we examine the
      efferent projections of 35 neurons located in the SNr region where these SNc cell
      clusters reside. The neuronal cell body was injected with biotinylated dextran
      amine so as to trace each complete axon in the sagittal or the coronal plane.
      Electrophysiological guidance guaranteed that the tracer was ejected among
      neurons displaying a typical SNc discharge pattern. Furthermore, double
      immunofluorescence and immunohistochemical labeling ensured that the tracer
      deposits were placed within the DA cell clusters. Three types of projection
      neurons occurred in the SNc ventral tier cell cluster region: type I neurons,
      projecting to basal ganglia; type II neurons, targeting both the basal ganglia
      and thalamus; and type III neurons, projecting only to the thalamus. The striatum
      was targeted by most of the type I and II neurons and the innervation reached
      both the striosome/subcallosal streak and matrix compartments. Many nigrostriatal
      fibers provided collaterals to the globus pallidus and, less frequently, to the
      subthalamic nucleus. At a thalamic level, type II and III neurons preferentially
      targeted the reticular, ventral posterolateral, and ventral medial nuclei. Our
      results reveal that the SNr region where DA ventral tier cell clusters reside
      harbors neurons projecting to the basal ganglia and/or the thalamus, thus
      suggesting that neurodegeneration of nigral neurons in Parkinson's disease might
      affect various extrastriatal basal ganglia structures and multiple thalamic
      nuclei.

PMID- 20151361
TI  - KCNQ5 reaches synaptic endings in the auditory brainstem at hearing onset and
      targeting maintenance is activity-dependent.
AB  - Kv7.5/KCNQ5, a voltage-dependent potassium channel that generates a subthreshold
      K+ current (also called M-current), is localized in excitatory endings of
      auditory brainstem nuclei in the adult rat. Here, we focus on how specific
      targeting develops from birth to adulthood in the rat. We first analyzed by
      immunocytochemistry the distribution of KCNQ5 during postnatal development of
      neurons in the anteroventral cochlear nucleus (AVCN) and their targets in the
      medial nucleus of the trapezoid body (MNTB). From postnatal days (P) 0 to 12,
      KCNQ5 immunoreactivity was restricted to cell bodies, whereas from P13 onward a
      shift in labeling pattern was seen, with KCNQ5 immunoreactivity becoming confined
      to synaptic endings in both the AVCN and MNTB. The developmental synaptic
      targeting was also accompanied by a downregulation of KCNQ5 transcripts in the
      cochlear nucleus from P13 onward, as seen with quantitative reverse transcriptase
      polymerase chain reaction. We further tested whether auditory nerve activity at
      hearing onset (approximately P12) regulates synaptic targeting of the channel.
      Cochleae were removed at P10, before hearing onset. In the MNTB, 3 days after
      cochlear ablation, at P13, KCNQ5 immunoreactivity was seen in calyces of Held, as
      in normal age-matched controls. However, immunolabeling virtually disappeared
      from MNTB calyces 40 days after cochlear ablation but reappeared in the somata of
      neurons in AVCN. These findings suggest that synaptic targeting of KCNQ5 in
      brainstem auditory neurons occurs around the time of hearing onset, regardless of
      auditory nerve activity. However, long-term synaptic localization after hearing
      onset depends on peripheral input.

PMID- 20151362
TI  - Ultrastructural relationships between cortical, thalamic, and amygdala
      glutamatergic inputs and group I metabotropic glutamate receptors in the rat
      accumbens.
AB  - Changes in glutamatergic transmission in the nucleus accumbens play a key role in
      mediating reward-related behaviors and addiction to psychostimulants.
      Glutamatergic inputs to the accumbens originate from multiple sources, including
      the prefrontal cortex, basolateral amygdala, and midline thalamus. The group I
      metabotropic glutamate receptors (mGluRs) are found throughout the core and shell
      of the nucleus accumbens, but their localization and function at specific
      glutamatergic synapses remain unknown. To further characterize the substrate that
      underlies group I mGluR functions in the accumbens, we combined anterograde tract
      tracing method with electron microscopy immunocytochemistry to study the
      ultrastructural relationships between specific glutamatergic afferents and
      mGluR1a- or mGluR5-containing neurons in the rat nucleus accumbens. Although
      cortical, thalamic, and amygdala glutamatergic terminals contact both mGluR1a-
      and mGluR5-immunoreactive dendrites and spines in the shell and core of the
      accumbens, they do so to varying degrees. Overall, glutamatergic terminals
      contact mGluR1a-positive spines about 30% of the time, whereas they form synapses
      twice as frequently with mGluR5-labeled spines. At the subsynaptic level, mGluR5
      is more frequently expressed perisynaptically and closer to the edges of
      glutamatergic axospinous synapses than mGluR1a, suggesting a differential degree
      of activation of the two group I mGluRs by transmitter spillover from
      glutamatergic synapses in the rat accumbens. These results lay the foundation for
      a deeper understanding of group I mGluR-mediated effects in the ventral striatum,
      and their potential therapeutic benefits in drug addiction and other
      neuropsychiatric changes in reward-related behaviors.

PMID- 20151364
TI  - Actions of motor neurons and leg muscles in jumping by planthopper insects
      (hemiptera, issidae).
AB  - To understand the catapult mechanism that propels jumping in a planthopper
      insect, the innervation and action of key muscles were analyzed. The large
      trochanteral depressor muscle, M133b,c, is innervated by two motor neurons and by
      two dorsal unpaired median (DUM) neurons, all with axons in N3C. A smaller
      depressor muscle, M133a, is innervated by two neurons, one with a large-diameter
      cell body, a large, blind-ending dendrite, and a giant ovoid, axon measuring 50
      microm by 30 microm in nerve N5A. The trochanteral levator muscles (M132) and
      (M131) are innervated by N4 and N3B, respectively. The actions of these muscles
      in a restrained jump were divisible into a three-phase pattern. First, both hind
      legs were moved into a cocked position by high-frequency bursts of spikes in the
      levator muscles lasting about 0.5 seconds. Second, and once both legs were
      cocked, M133b,c received a long continuous sequence of motor spikes, but the two
      levators spiked only sporadically. The spikes in the two motor neurons to M133b,c
      on one side were closely coupled to each other and to the spikes on the other
      side. If one hind leg was cocked then the spikes only occurred in motor neurons
      to that side. The final phase was the jump movement itself, which occurred when
      the depressor spikes ceased and which lasted 1 ms. Muscles 133b,c activated
      synchronously on both sides, are responsible for generating the power, and M133a
      and its giant neuron may play a role in triggering the release of a jump.

PMID- 20151363
TI  - Quantitative analysis of pre- and postsynaptic sex differences in the nucleus
      accumbens.
AB  - The nucleus accumbens (NAc) plays a central role in motivation and reward. While
      there is ample evidence for sex differences in addiction-related behaviors,
      little is known about the neuroanatomical substrates that underlie these sexual
      dimorphisms. We investigated sex differences in synaptic connectivity of the NAc
      by evaluating pre- and postsynaptic measures in gonadally intact male and
      proestrous female rats. We used DiI labeling and confocal microscopy to measure
      dendritic spine density, spine head size, dendritic length, and branching of
      medium spiny neurons (MSNs) in the NAc, and quantitative immunofluorescence to
      measure glutamatergic innervation using pre- (vesicular glutamate transporter 1
      and 2) and postsynaptic (postsynaptic density 95) markers, as well as
      dopaminergic innervation of the NAc. We also utilized electron microscopy to
      complement the above measures. Clear but subtle sex differences were identified,
      namely, in distal dendritic spine density and the proportion of large spines on
      MSNs, both of which are greater in females. Sex differences in spine density and
      spine head size are evident in both the core and shell subregions, but are
      stronger in the core. This study is the first demonstration of neuroanatomical
      sex differences in the NAc and provides evidence that structural differences in
      synaptic connectivity and glutamatergic input may contribute to behavioral sex
      differences in reward and addiction.

PMID- 20151371
TI  - Donation of explanted pacemakers for reuse in underserved nations.
AB  - Some charitable organizations and physicians are willing to assist in the
      compassionate donation of explanted pacemakers for reuse in medically underserved
      nations. However, healthcare organizations must recognize that the Food and Drug
      Administration (FDA), device manufacturers, professional societies and many
      physicians advocate return of explanted pacemakers to the manufacturer to ensure
      an accurate performance database promoting improved device reliability and safety
      for the patient.

PMID- 20151372
TI  - Effective in-service education requires more than subject expertise.
AB  - Several formal roles within the field of human performance and training are
      specifically responsible for ensuring that programs are designed and developed
      for maximum impact. Data show that education and training are essential functions
      of healthcare risk management professionals. For this, healthcare risk management
      professionals can maximize their training efforts by partnering with an
      instructional designer or developer to create a training program that promotes
      safe and trusted healthcare.

PMID- 20151366
TI  - Classification of eating disturbance in children and adolescents: proposed
      changes for the DSM-V.
AB  - Childhood and adolescence are critical periods of neural development and physical
      growth. The malnutrition and related medical complications resulting from eating
      disorders such as anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder
      not otherwise specified may have more severe and potentially more protracted
      consequences during youth than during other age periods. The consensus opinion of
      an international workgroup of experts on the diagnosis and treatment of child and
      adolescent eating disorders is that (a) lower and more developmentally sensitive
      thresholds of symptom severity (e.g. lower frequency of purging behaviours,
      significant deviations from growth curves as indicators of clinical severity) be
      used as diagnostic boundaries for children and adolescents, (b) behavioural
      indicators of psychological features of eating disorders be considered even in
      the absence of direct self-report of such symptoms and (c) multiple informants
      (e.g. parents) be used to ascertain symptom profiles. Collectively, these
      recommendations will permit earlier identification and intervention to prevent
      the exacerbation of eating disorder symptoms.

PMID- 20151365
TI  - Regional heterogeneity in astrocyte responses following contusive spinal cord
      injury in mice.
AB  - Astrocytes and their precursors respond to spinal cord injury (SCI) by
      proliferating, migrating, and altering phenotype. This contributes to glial scar
      formation at the lesion border and gliosis in spared gray and white matter. The
      present study was undertaken to evaluate astrocyte changes over time and
      determine when and where interventions might be targeted to alter the astrocyte
      response. Bromodeoxyuridine (BrdU) was administered to mice 3 days after SCI, and
      cells expressing BrdU and the astrocyte marker, glial fibrillary acidic protein
      (GFAP), were counted at 3, 7, and 49 days post-injury (DPI). BrdU-labeled cells
      accumulated at the lesion border by 7 DPI and approximately half of these
      expressed GFAP. In spared white matter, the total number of BrdU+ cells
      decreased, while the percentage of BrdU+ cells expressing GFAP increased at 49
      DPI. Phenotypic changes were examined using the progenitor marker nestin, the
      radial glial marker, brain lipid binding protein (BLBP), and GFAP. Nestin was
      upregulated by 3 DPI and declined between 7 and 49 DPI in all regions, and GFAP
      increased and remained above naive levels at all timepoints. BLBP increased early
      and remained high along the lesion border and spared white matter, but was
      expressed transiently by cells lining the central canal and in a unique
      population of small cells found within the lesion and in gray matter rostral and
      caudal to the border. The results demonstrate that the astrocyte response to SCI
      is regionally heterogeneous, and suggests astrocyte populations that could be
      targeted by interventions.

PMID- 20151373
TI  - Reducing the new employee learning curve to improve productivity.
AB  - Effective onboarding is essential to the acclimation and socialization of new
      healthcare risk management professionals within their new organizations. This
      acclimation process is a natural extension of employee orientation training.
      Benefits of effective onboarding include maximizing new employees' full
      productivity in core functions, thereby recouping the organization's return on
      investment, and positioning them for enduring success.

PMID- 20151374
TI  - Plaintiff's attorneys share perspectives on patient communication.
AB  - This article reports that malpractice attorneys representing plaintiffs accept a
      small percentage of the clients who request legal representation for medical
      liability claims. Of those cases they do not accept, these attorneys report that
      a significant motivator for patients seeking legal counsel is poor clinician
      patient communication. They cite poor listening skills; delegation of critical
      consent communication; failure to share timely information with colleagues and
      nursing personnel; failure to have meaningful, empathetic conversations when
      adverse outcomes occur; and defensive behavior when patients seek to learn more
      by questioning diagnoses and treatment options.

PMID- 20151375
TI  - In healthcare, is the human being an asset or liability?
AB  - This article contrasts the application of preventive and predictive technologies
      in industry to those in healthcare. For years, risk managers have been discussing
      the rationing of care. This article presents the perspective of an engineering
      professional from the manufacturing industry who now consults with healthcare
      risk managers. The human being is often referred to as an "asset" in our society.
      Do we actually treat people as assets or liabilities? When preventive maintenance
      is routinely performed on a piece of equipment, the benefits are more reliable
      operations, increased productivity, and lower life cycle costs. If these
      proactive concepts are applied to the human body within our current healthcare
      systems, will we see these same benefits?

PMID- 20151376
TI  - Case law update: a review of recent rulings of interest to risk managers. Talbott
      v. Roswell Hospital Corporation, 144 N.M. 753, 192 P.3d 267 (Ct. App. N.M.2009).

PMID- 20151377
TI  - The resurgence of acyclic nucleic acids.
AB  - This review examines acyclic nucleoside analogs as therapeutic agents, potential
      progenitor candidates to RNA, and novel building blocks for nucleic-acid
      nanotechnology. Together, these areas of research provide new insights into the
      structural and functional properties of nucleic acids and suggest new paradigms
      for nucleic acid self-assembly.

PMID- 20151378
TI  - Tropane alkaloids from Erythroxylum genus: distribution and compilation of 13C
      NMR spectral data.
AB  - Erythroxylum, the most representative genus of the Erythroxylaceae family,
      presents tropane alkaloids as main constituents. This class of compounds greatly
      contributes to the chemotaxonomic characterization of plants of this genus, and
      it has important medical uses and shows toxic effects. This review describes 186
      tropane alkaloids in the 35 species of Erythroxylum distributed worldwide. In
      addition, a compilation of their (13)C-NMR spectral data is presented.

PMID- 20151379
TI  - Exotic DNAs made of nonnatural bases and natural phosphodiester bonds.

PMID- 20151381
TI  - Phytochemicals and biological activities of Pulicaria species.

PMID- 20151380
TI  - Phytochemical and biological studies of plants from the genus Phlomis.

PMID- 20151382
TI  - Synthesis and biophysical properties of oligodeoxynucleotides containing 2'-deoxy
      5-(4-nitro-1H-imidazol-1-yl)-beta-D-uridine and 2'-deoxy-5-(1,3-dioxo-1H
      benzo[de]isoquinolin-2(3H)-yl)-beta-D-uridine monomers.
AB  - Detection of single-nucleotide polymorphisms (SNPs) of biologically relevant DNA
      and RNA samples remain a scientific and practical challenge. We have synthesized
      phosphoramidite building blocks and oligodeoxynucleotide probes containing novel
      2'-deoxyuridine monomers modified by 5-(4-nitro-1H-imidazol-1-yl; (monomer X) or
      2'-deoxy-5-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl; monomer Y) substituents.
      The effects of monomers X and Y on duplex thermal stability, and their capability
      towards discrimination of single-base mismatches were furthermore studied.
      Encouraging results were obtained with respect to thermal mismatch discrimination
      using oligodeoxynucleotides containing monomer X and fluorescence-based
      discrimination using oligodeoxynucleotides containing monomer Y.

PMID- 20151383
TI  - Studies of amyloid-like fibrillogenesis through beta-sheet-mediated self-assembly
      of short synthetic peptides.
AB  - Three structurally different types of small peptides, namely, i) Boc-Ile-Aib-Ile
      OMe (Aib=alpha-aminoisobutyric acid), ii) Boc-Xx-m-aminobenzoic acid (Xx=beta-Ala
      and gamma-aminobutyric acid), and iii) Boc-Xx-m-nitroaniline, were found to
      exhibit beta-sheet-mediated fibrillogenesis in the solid state, revealed by FT
      IR, single-crystal X-ray diffraction, and FE-SEM studies. Interestingly, the
      fibrils grown from peptides 2 and 3 were found to bind with the physiological dye
      Congo red, a characteristic feature of amyloid fibrils.

PMID- 20151384
TI  - Component analysis and free radical-scavenging potential of Panax notoginseng and
      Carthamus tinctorius extracts.
AB  - Panax notoginseng and Carthamus tinctorius are known as traditional medicinal
      plants, and they also have edible values. To better understand their
      pharmacological mechanism, the present study assessed the in vitro antioxidant
      activities of extracts of P. notoginseng (EPN) and C. tinctorius (ECT). In
      addition, the main components of EPN and ECT were determined by HPLC. The results
      show that EPN mainly contained saponins, which were effective in scavenging (.)OH
      and O(.)(2-), while showing a low activity in the DPPH(.) assay. Flavonoids were
      the main components of ECT and were active in scavenging all three radicals in a
      dose-dependent manner. In brief, the antioxidant properties of EPN and ECT are
      distinct and might be complementary, their combined use tending to be more
      effective in scavenging (.)OH (P<0.05 vs. EPN or ECT).

PMID- 20151385
TI  - Two new sesquiterpene derivatives from the Tunisian endemic Ferula tunetana Pom.
AB  - A new sesquiterpene ester, tunetanin A (1), a new sesquiterpene coumarin,
      tunetacoumarin A (2), together with eight known compounds, i.e., coladin (3),
      coladonin (4), isosmarcandin (5), 13-hydroxyfeselol (6), umbelliprenin (7)
      propiophenone (8), beta-sitosterol (9), and stigmasterol (10), were isolated from
      the roots of Ferula tunetana. Their structures were elucidated on the basis of
      extensive spectroscopic methods, including 1D- and 2D-NMR experiments and MS
      analysis, as well as by comparison with published data. The cytotoxicity of
      compounds 1-7 towards two human colon cancer cell lines, HT-29 and HCT 116, was
      evaluated. Compounds 3, 4, and 6 showed weak cytotoxic activities.

PMID- 20151386
TI  - Triplex-stabilizing properties of parallel clamps carrying LNA derivatives at the
      Hoogsteen strand.
AB  - DNA Parallel clamps with a polypurine strand linked to a polypyrimidine Hoogsteen
      strand containing locked nucleic acids bind their corresponding polypyrimidine
      targets with high affinity.

PMID- 20151387
TI  - Inhibition of lipopolysaccharide-induced nitric oxide production by antofine and
      its analogues in RAW 264.7 macrophage cells.
AB  - Based on the anti-inflammatory activity of phenanthroindolizidine alkaloids, the
      inhibitory effect of antofine and its analogues on lipopolysaccharide (LPS)
      induced nitric oxide (NO) production was examined, and structure-activity
      relationships are discussed. Antofine and several analogues suppressed NO
      production in LPS-stimulated RAW 264.7 cells. The MeO group at C(2), and the
      bulkiness of the substituents at C(3) and C(6) in the phenanthrene ring might be
      critical for this effect. Besides, regulation of iNOS expression might be
      involved in the inhibitory effect of antofine on LPS-induced NO production in
      macrophage cells.

PMID- 20151388
TI  - Habitat-dependent variations in berberine content of Berberis asiatica Roxb. ex.
      DC. in Kumaon, Western Himalaya.
AB  - The variation of the berberine content in roots and stem bark of Berberis
      asiatica with altitude and edaphic conditions in the western Himalaya was
      estimated by HPLC. The comparative assessment revealed a significantly higher
      berberine content in roots than in stem barks. Moreover, the berberine content
      varied significantly with altitude and edaphic conditions both in root and stem
      bark samples. The populations growing at low altitude contained significantly
      more berberine than the ones growing at high altitude. Also the moisture and
      potassium (K) percentage of the soil significantly influenced the berberine
      content.

PMID- 20151389
TI  - Screening of biological activities of a series of chalcone derivatives against
      human pathogenic microorganisms.
AB  - In an effort to develop new antimicrobial agents, a series of chalcone
      derivatives, 3-60, were prepared by Claisen-Schmidt condensation of appropriate
      acetophenones and 2-furyl methyl ketones with appropriate aromatic aldehydes,
      furfural, and thiophene-2-carbaldehyde in an aqueous solution of NaOH and EtOH at
      room temperature. The synthesized compounds were characterized by means of their
      IR- and NMR-spectral data, and elemental analysis. All compounds were tested for
      their antibacterial and antifungal activities by the disc diffusion method. For
      the most active compounds, also minimum inhibitory concentrations (MICs) were
      determined.

PMID- 20151390
TI  - Easy production of a glycolipid analogue using animal cells in culture.
AB  - A glycolipid analogue, GM4-type ganglioside, was obtained by a combination of
      chemical synthesis and biosynthetic processes in animal cells with dodecyl beta-D
      galactoside (Gal C12) as primer. The primer was conveniently prepared in two
      steps: glycosylation, followed by deacetylation. The primer was introduced to
      mouse melanoma B16 cells to serve as substrate for cellular, enzyme-catalyzed
      glycosylation. Incubation of the cells in the presence of the primer resulted in
      sialylation of the galactose residue to afford a GM4 analogue that was released
      from the cells to the culture medium. The strategy of preparation of the GM4
      analogue described in this study is a viable alternative to the existing methods.
      The saccharide-primer method is fast, convenient, not requiring expensive enzymes
      and glycosyl donors, and highly stereoselective.

PMID- 20151391
TI  - Bioactive compounds with added value prepared from terpenes contained in solid
      wastes from the olive oil industry.
AB  - Starting from solid wastes from two-phase olive-oil extraction, the pentacyclic
      triterpenes oleanolic acid and maslinic acid were isolated. These natural
      compounds were transformed into methyl olean-12-en-28-oate (5), which then was
      transformed into several seco-C-ring triterpene compounds by chemical and
      photolytic modifications. The triene seco-products were fragmented through
      several oxidative procedures to produce, simultaneously, cis- and trans-decalin
      derivatives, both potential synthons for bioactive compounds. The chemical
      behavior of the isolated fragments was investigated, and a suitable approach to
      several low-molecular-weight terpenes was performed. These are interesting
      processes for the value-addition to solid waste from the olive-oil industry.

PMID- 20151393
TI  - Volatile compounds from Melicope obscura.
AB  - To evaluate the interpopulation variability of volatile compounds in Melicope
      obscura, four samples representing four populations were collected all over the
      distribution area of the species in Reunion Island (Indian Ocean). The samples
      were extracted by hydrodistillation, and analyzed using GC/FID and GC/MS
      techniques. The study revealed that, in the four essential oils obtained,
      oxygenated sesquiterpenes were one of the major chemical classes (9.2-35.2%),
      mainly consisting of a new compound, (+)-6-ethenyl-2-hydroxy-6,10-dimethylundeca
      2,9-dien-4-one (1), called melicopenol (8.6-30.1%). The compound was isolated by
      column chromatography and identified by spectral analyses including 1D- and 2D
      NMR.

PMID- 20151392
TI  - Chemical composition and antimicrobial activity of the essential oils from
      several Hypericum taxa (Guttiferae) growing in central Italy (Appennino Umbro
      Marchigiano).
AB  - The chemical composition of the essential oils of nine taxa from seven sections
      of Hypericum L. (Guttiferae; H. perforatum subsp. perforatum, H. perforatum
      subsp. veronense, H. calycinum, H. montanum, H. richeri subsp. richeri, H.
      hyssopifolium, H. hirsutum, H. hircinum subsp. majus, and H. tetrapterum)
      occurring in central Italy (Appennino Umbro-Marchigiano) was analyzed by GC/FID
      and GC/MS. A total of 186 compounds were identified in the different species and
      subspecies, accounting for 86.9-92.8% of the total oils. The major fraction of
      the oil was always represented by sesquiterpene hydrocarbons (30.3-77.2%), while
      quantitative differences occurred between the other classes of volatiles
      depending on the taxa considered. Chemical composition of the nine Hypericum
      entities with respect to the taxonomical classification was discussed. Essential
      oils obtained from six taxa, i.e., H. perforatum subsp. perforatum, H. perforatum
      subsp. veronense, H. calycinum, H. richeri subsp. richeri, H. hirsutum and H.
      tetrapterum, were also tested for their antimicrobial properties against five
      different microbial strains by the broth-microdilution method, and they were
      found to have significant activity (expressed as MIC) on B. subtilis, moderate
      activity on C. albicans and S. aureus, and weak activity on E. coli and E.
      faecalis, the most active being those from H. hirsutum, H. richeri subsp.
      richeri, and H. tetrapterum.

PMID- 20151394
TI  - Metal(II)-ligand molar ratio dependence of enantioseparation of tartaric acid by
      ligand exchange CE with Cu(II) and Ni(II)-D-quinic acid systems.
AB  - Enantioseparation of tartaric acid by ligand exchange CE with a Cu(II)-D-quinic
      acid system was studied. Racemic tartaric acid was enantioseparated by ligand
      exchange CE using BGEs containing relatively low Cu(II)-D-quinic acid molar
      ratios ranging from 1:1 to 1:3 and high molar ratios ranging from 1:8 to 1:12 but
      was not enantioseparated using BGEs with medium molar ratios ranging from 1:4 to
      1:6. While the migration order of D-tartaric acid was prior to L-tartaric acid at
      the lower Cu(II)-D-quinic acid molar ratios, the enantiomer migration order was
      reversed at the higher molar ratios. These results were compared with those for
      Ni(II)-D-quinic acid system. The molar ratio dependence of enantiomer migration
      order can be attributed to a change in the coordination structure of Cu(II) ion
      with D-quinic acid.

PMID- 20151395
TI  - Analysis of DNA complexes with small solutes by CE with LIF detection.
AB  - In this article, we describe the analysis of aptamers for Hg(2+) ions through CE
      with LIF (CE-LIF) detection using 2% poly(ethylene oxide) solutions containing
      OliGreen (fluorophore). In the presence of an EOF, DNA strands migrating against
      the EOF were detected at the cathode end. Four DNA strands - T(33), T(5)C(28),
      T(5)C(5)T(23), and T(15)C(5)T(13) - could not be separated through CE-LIF in the
      absence of Hg(2+). At 0.3 mM Hg(2+), however, all four were partially separated
      within 20 min, with SDs of the migration times all being less than 2.5%. From the
      CE, fluorescence, and ellipticity data, we concluded that the conformations of
      these four DNA strands all changed from random-coil to folded structures as a
      result of T-Hg(2+)-T bonding. In addition, we found that this CE approach
      provided different electropherograms patterns for T(7), T(15), and T(33) in the
      absence and presence of Hg(2+), indicating various interactions of the DNA
      strands with Hg(2+). Using this simple, high-resolution CE approach, we also
      demonstrated that adenosine triphosphate has a stronger interaction with the
      adenosine triphosphate aptamer than with either the platelet-derived growth
      factor aptamer or T(33). This CE approach holds great potential for screening
      aptamers for small solutes, studying the catalytic activity of DNAzymes, and
      evaluating the biological functions of microRNA.

PMID- 20151396
TI  - Capacitively coupled contactless conductivity detection with dual top-bottom cell
      configuration for microchip electrophoresis.
AB  - An optimized capacitively coupled contactless conductivity detector for microchip
      electophoresis is presented. The detector consists of a pair of top-bottom
      excitation electrodes and a pair of pickup electrodes disposed onto a very thin
      plastic microfluidic chip. The detection cell formed by the electrodes is
      completely encased and shielded in a metal housing. These approaches allow for
      the enhancement of signal coupling and extraction from the detection cell that
      result in an improved signal-to-noise-ratio and detection sensitivity. The
      improved detector performance is illustrated by the electrophoretic separation of
      six cations (NH(4) (+), K(+), Ca(2+), Na(+), Mg(2+), Li(+)) with a detection
      limit of approximately 0.3 microM and the analysis of the anions (Br(-), Cl(-),
      NO(2) (-), NO(3) (-), SO(4) (2-), F(-)) with a detection limit of about 0.15
      microM. These LODs are significantly improved compared with previous reports
      using the conventional top-top electrode geometry. The developed system was
      applied to the analysis of ions in bottled drinking water samples.

PMID- 20151397
TI  - Differential characterization of biogenic amine-producing bacteria involved in
      food poisoning using MALDI-TOF mass fingerprinting.
AB  - Histamine poisoning is caused by the consumption of fish and other foods that
      harbor bacteria possessing histidine decarboxylase activity. With the aim of
      preventing histamine formation, highly specific mass spectral fingerprints were
      obtained from the 16 major biogenic amine-producing enteric and marine bacteria
      by means of MALDI-TOF MS analysis. All bacterial strains analyzed exhibited
      specific spectral fingerprints that enabled its unambiguous differentiation. This
      technique also identified peaks common to certain bacterial groups. Thus, two
      protein peaks at m/z 4182+/-1 and 8363+/-6 were found to be present in all
      Enterobacteriaceae species analyzed except for Morganella morganii. Peaks at m/z
      3635+/-1 and 7267+/-2 were specific to both M. morganii and Proteus spp. Biogenic
      amine-forming Proteus spp. exhibited three genus-specific peaks at m/z 3980,
      7960+/-1 and 9584+/-2. The genus Photobacterium also showed three genus-specific
      peaks at m/z 2980+/-1, 4275+/-1 and 6578+/-1. The two histamine-producing Gram
      positive bacteria Lactobacillus sp. 30A and Staphylococcus xylosus exhibited a
      few protein peaks in the 2000-7000 m/z range and could be easily distinguished
      from biogenic amine-forming Gram-negative bacteria. Clustering based on MALDI-TOF
      MS also exhibited a good correlation with phylogenetic analysis based on the 16S
      rRNA gene sequence, validating the ability of the MALDI-TOF technique to
      establish relationships between microbial strains and species. The approach
      described in this study leads the way toward the rapid and specific
      identification of major biogenic amine-forming bacteria based on molecular
      protein markers with a goal to the timely prevention of histamine food poisoning.

PMID- 20151398
TI  - Determination of the influence of IR radiation on the antioxidative network of
      the human skin.
AB  - Production of free radicals in the human skin subsequent to IR irradiation has
      been demonstrated by means of two different methods. The first technique, based
      on resonance Raman spectroscopy, enables the non-invasive measurements of the
      kinetics of cutaneous carotenoid antioxidants beta-carotene and lycopene,
      subsequent to IR irradiation. Obtained degradation of the cutaneous carotenoids
      was a hint but not evidence that IR irradiation can produce free radicals in the
      skin. Therefore, the direct observation sustaining the production of free
      radicals subsequent to IR irradiation in the skin was performed in-vitro by
      electron paramagnetic resonance spectroscopy. Enzymatic processes as well as heat
      shock-induced radicals in the human skin are presumably involved in the energy
      transfer from IR irradiation into the molecules of the skin. Protection strategy
      for human skin against IR-induced free radicals based on the increase in the
      concentration of antioxidants by means of antioxidant-rich supplementation is
      discussed.

PMID- 20151399
TI  - Changes in employment status and experience of discrimination among cancer
      patients: findings from a nationwide survey in Korea.
AB  - BACKGROUND: As the number of working cancer patients increases, workplace
      discrimination and its relationship to changes in employment status among cancer
      patients is becoming an increasingly important social concern. The aim of this
      study is to provide a comprehensive overview of the relationship between changes
      in employment status and discrimination following a diagnosis of cancer. METHODS:
      A total of 748 cancer patients, aged 18 years and older, who were employed before
      receiving a diagnosis of cancer, were enrolled in this study. Patients were
      recruited from ten cancer centers in Korea. Sociodemographic data, work-related
      data, and clinical information, as well as information on changes in employment
      status and incidences of discrimination, were collected from all patients.
      RESULTS: A change in employment status was reported by 73.4% of the sample, with
      unemployment being the most common change (46.4%). Forty-two (5.6%) patients
      reported that they had experienced discrimination in the workplace. Reports of
      discrimination were only weakly correlated with changes in employment status, but
      were significantly correlated with forced unemployment. Additional analyses
      revealed that being female, being from a lower socioeconomic status group and
      having a disability were risk-factors for unemployment, while being male, being
      from a higher socioeconomic status group and having a disability were risk
      factors for workplace discrimination or forced unemployment. CONCLUSIONS: More
      attention should be paid to vulnerable who are diagnosed with cancer. An
      individualized and culture-based approach should be taken to minimize undesirable
      changes in employment status and to reduce discrimination among patients
      receiving a diagnosis of cancer.

PMID- 20151400
TI  - Simultaneous quantification of 14 bioactive constituents in Forsythia suspensa by
      liquid chromatography-electrospray ionisation-mass spectrometry.
AB  - INTRODUCTION: Forsythia suspensa is a commonly used traditional Chinese medicine
      including phenylethanoid glycosides, lignans, flavonoids, terpenes and volatile
      oils. Quantification of multi-components is important for the quality control of
      Forsythia suspensa. OBJECTIVE: To establish a liquid chromatography-electrospray
      ionisation-mass spectrometry method for simultaneous quantification of 14
      bioactive constituents of Forsythia suspensa in different places of China and
      different parts of this herb. METHODOLOGY: The optimal chromatographic conditions
      were achieved on a Kromasil C(18) column (150 yen 4.6 mm, 5 microm) with gradient
      elution of methanol, acetonitrile and 0.1% formic acid in 27 min. Detection was
      performed in negative ionisation mode by monitoring the precursor-product
      combination in multiple reaction monitoring (MRM) mode. The validation of the
      method included tests of linearity, sensitivity, precision, repeatability,
      stability and accuracy. RESULTS: All calibration curves showed good linear
      regression (r > 0.9990) within test ranges. The established method showed good
      precision and accuracy with overall intra-day and inter-day variations of 0.7-4.3
      and 1.1-3.9% respectively, and overall recoveries of 96.65-101.2% for the
      compounds analysed. CONCLUSION: The proposed method was successfully applied for
      the quantitative analysis of 14 constituents in 12 Forsythia suspensa samples.

PMID- 20151402
TI  - The acquisition of an inheritable 50-bp deletion in the human mtDNA control
      region does not affect the mtDNA copy number in peripheral blood cells.
AB  - The mitochondrial DNA (mtDNA) control region is believed to play an important
      biological role in mtDNA replication. Large deletions in this region are rarely
      found, but when they do occur they might be expected to interfere with the
      replication of the molecule, thus leading to a reduction of mtDNA copy number.
      During a survey for mtDNA sequence variations in 5,559 individuals from the
      general Chinese population and 2,538 individuals with medical disorders, we
      identified a 50-bp deletion (m.298_347del50) in the mtDNA control region in a
      member of a healthy Han Chinese family belonging to haplogroup B4c1b2, as
      suggested by complete mtDNA genome sequencing. This deletion removes the
      conserved sequence block II (CSBII; region 299-315) and the replication primer
      location (region 317-321). However, quantification of the mtDNA copy number in
      this subject showed a value within a range that was observed in 20 healthy
      subjects without the deletion. The deletion was detected in the hair samples of
      the maternal relatives of the subject and exhibited variable heteroplasmy. Our
      current observation, together with a recent report for a benign 154-bp deletion
      in the mtDNA control region, suggests that the control of mtDNA replication may
      be more complex than we had thought.

PMID- 20151403
TI  - Massively parallel sequencing of ataxia genes after array-based enrichment.
AB  - Massively parallel sequencing has tremendous diagnostic potential but requires
      enriched templates for sequencing. Here we report the validation of an array
      based sequence capture method in genetically heterogeneous disorders. The model
      disorder selected was AR ataxia, using five subjects with known mutations and two
      unaffected controls. The genomic sequences of seven disease genes, together with
      two control loci were targeted on a 2-Mb sequence-capture array. After
      enrichment, the patients' DNA samples were analyzed using one-quarter Roche GS
      FLX Titanium sequencing run, resulting in an average of 65 Mb of sequence data
      per patient. This was sufficient for an average 25-fold coverage/base in all
      targeted regions. Enrichment showed high specificity; on average, 80% of uniquely
      mapped reads were on target. Importantly, this approach enabled automated
      detection of deletions and hetero- and homozygous point mutations for 6/7 mutant
      alleles, and greater than 99% accuracy for known SNP variants. Our results also
      clearly show reduced coverage for sequences in repeat-rich regions, which
      significantly impacts the reliable detection of genomic variants. Based on these
      findings we recommend a minimal coverage of 15-fold for diagnostic implementation
      of this technology. We conclude that massive parallel sequencing of enriched
      samples enables personalized diagnosis of heterogeneous genetic disorders and
      qualifies for rapid diagnostic implementation.

PMID- 20151404
TI  - The ubiquitin ligase CHIP/STUB1 targets mutant keratins for degradation.
AB  - Keratin (K) intermediate filament proteins form cytoskeletal scaffolds in
      epithelia, the disruption of which leads to a large number of human disorders.
      KRT5 or KRT14 mutations cause epidermolysis bullosa simplex (EBS). The
      considerable intra- and interfamilial variability in EBS suggests modifying loci,
      most of which are unknown. In many human disorders, chaperones and the ubiquitin
      proteasome system have been found to modify disease severity, thereby providing
      novel therapy targets. Here, we demonstrate upregulation of stress-induced Hsp70
      and Hsp90 in two EBS models, namely, in neonatal K5(-/-) mice and upon proteasome
      inhibition in cells that stably express the disease-causing mutation K14
      p.Arg125Cys, both harboring keratin aggregates. Furthermore, proteasome
      inhibition caused nuclear translocation of pHSF-1 and an increase in K14
      p.Arg125Cys-positive aggregates in cells. Overexpression of the chaperone
      associated ubiquitin ligase CHIP/STUB1 strongly reduced keratin aggregates
      through increased degradation of mutant K14. Using CHIP-p.Met1_Ala142del
      (DeltaTPR-CHIP), we demonstrated the involvement of Hsc70 and Hsp70 in mutant
      keratin degradation. Our data uncover common principles between EBS and other
      protein misfolding disorders, revealing that aggregation-prone keratins are
      targeted by components of the chaperone machinery. Thus, modulation of the
      chaperone machinery using small molecules may represent a novel therapeutic
      strategy for dominant EBS, allowing reformation of an intact keratin
      cytoskeleton.

PMID- 20151405
TI  - Genetic analysis of von Hippel-Lindau disease.
AB  - Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease,
      congenital polycythemia, and are found in many sporadic tumor types as well.
      Reports of VHL mutations are dispersed throughout original articles and databases
      that have not been recently updated. We compiled a comprehensive mutation table
      of 1,548 germline and somatic VHL mutations, derived from this protein of only
      213 amino acids. We describe detailed phenotype and gene mutation information for
      945 VHL families, including 30 previously unpublished kindreds from The
      Netherlands (six novel mutations). These data represent the most extensive
      catalog of germline VHL mutations to date. We also review VHL disease, known and
      theorized pathogenesis of common VHL manifestations, and genotype-phenotype
      correlations. Analysis of all VHL families, excluding germline mutations
      resulting in congenital polycythemias, describes the spectrum of mutation types:
      52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11%
      large/complete deletions, and 7% splice mutations. This easy-to-use compilation
      of VHL mutations is intended to facilitate research and function as a necessary
      adjunct for physicians when providing patient information.

PMID- 20151406
TI  - Suppression of pine wilt disease by an antibacterial agent, oxolinic acid.
AB  - BACKGROUND: Pine wilt disease (PWD) is very complex and has been reported to be
      caused by pine wood nematode, Bursaphelenchus xylophilus (Steiner & Buhrer)
      Nickle, and its accompanying bacteria. However, there is no report on the control
      of PWD by antibacterial agent. The present study was performed to investigate
      disease control efficacy of antibacterial agents against PWD. RESULTS: Among six
      antibacterial antibiotics tested, oxolinic acid (OA) showed the strongest
      antibacterial activity against five bacteria isolated from three strains of pine
      wood nematode. In in vivo assay, it effectively suppressed the development of PWD
      in three-year-old seedlings of Pinus densiflora Sieb. & Zucc.; it showed 71%
      control when injected at 3 mg per seedling. A mixture of OA and the nematicidal
      agent abamectin (Ab) showed higher disease control efficacy against PWD than
      either OA or Ab alone. In addition, OA alone and a mixture of OA and Ab also
      controlled PWD in approximately 20-year-old pine trees under field conditions.
      CONCLUSION: This is the first report on the suppression of PWD by OA. The result
      strongly indicates that PWD could be controlled by antibacterial antibiotic alone
      and a combination of antibacterial and nematicidal agents.

PMID- 20151407
TI  - The developmental reduction of the marsupial coracoid: a case study in
      Monodelphis domestica.
AB  - During their embryogenesis, marsupials develop a unique structure, the shoulder
      arch, which provides the structural and muscle-attachment support necessary for
      the newborn's crawl to the teat. One of the most pronounced and important aspects
      of the shoulder arch is an enlarged coracoid. After marsupial newborns reach the
      teat, the shoulder arch is remodeled and the coracoid is reduced to a small
      process on the scapula. Although an understanding of marsupial coracoid reduction
      has the potential to provide insights into both, marsupial evolution and the
      origin of mammals, little is known about the morphological and cellular processes
      controlling this process. To remedy this situation, this study examined the
      morphological and cellular mechanisms behind coracoid reduction in the gray short
      tailed opossum, Monodelphis domestica. A quantitative, morphometric study of
      shoulder girdle development revealed that the coracoid is reduced in size
      relative to other aspects of the shoulder girdle by growing at a slower rate.
      Using a series of molecular assays for cell death, no evidence was found for
      programmed cell death playing a role in the reduction of coracoid size in
      marsupials (in contrast to hypotheses of previous researchers). Although it is
      likely the case that coracoid growth is reduced through a relatively lower rate
      of cellular proliferation, differences in proliferative rates in the coracoid and
      scapula were not great enough to be quantified using standard molecular assays.

PMID- 20151408
TI  - Life is precious and I'm making the best of it: coping strategies of long-term
      cancer survivors.
AB  - OBJECTIVE: Coping strategies mediate the relationship between challenging
      situations and their impact on psychosocial outcomes. Many long-term cancer
      survivors continue to face a range of challenges in their daily lives, yet little
      is known about how this population copes. The study explored the prevalence and
      predictors of cancer-specific coping strategies among a heterogeneous sample of
      long-term cancer survivors. METHODS: A population-based cross-sectional sample of
      863 adult cancer survivors 5-6 years post-diagnosis completed a pen-and-paper
      survey. Cancer-specific coping was assessed via the Mini-Mental Adjustment to
      Cancer (mini-MAC) Scale. Potential predictor variables included patient, disease
      and treatment characteristics and social support. RESULTS: The most commonly used
      coping strategies were fatalism and fighting spirit. Of those survivors that used
      any of the coping strategies assessed, 53% used at least two strategies.
      Maladaptive coping was commonly predicted by low social support (OR = 1.77 to
      2.49) and being a disability pensioner, whereas having ever received chemotherapy
      widely predicted greater use of all types of coping. A weekly household income of
      over $1000 a week uniquely predicted not using any mini-MAC coping strategies.
      CONCLUSIONS: Survivors continue to engage in cancer-specific coping strategies
      many years after diagnosis, albeit to a lesser extent than recent survivor
      populations. A number of predictors were identified that can alert health workers
      to long-term survivors at increased risk of maladaptive coping. Given that low
      social support consistently predicted maladaptive coping responses, interventions
      aimed at promoting positive coping responses should include strategies to
      increase access to social support.

PMID- 20151409
TI  - Organizational determinants of work outcomes and quality care ratings among Army
      Medical Department registered nurses.
AB  - The Practice Environment Scale of the Nursing Work Index, the Maslach Burnout
      Inventory, and several single-item measures were administered to registered
      nurses (RNs) working within 23 U.S.-based Army Medical Department (AMEDD)
      hospitals. Data were analyzed with logistic regression for nested data.
      Unfavorable nursing practice environments had a substantial association with job
      dissatisfaction (OR 13.75, p < .01), emotional exhaustion (OR 12.70, p < .01),
      intent to leave (OR 3.03, p < .01), and fair to poor quality of care (OR 10.66, p
      < .01). This study provides the first system-wide analyses of nursing practice
      environments in AMEDD hospitals in the U.S. Similar to findings in civilian
      samples, poor quality work environments are associated with less favorable RN
      work outcomes and quality of care ratings.

PMID- 20151410
TI  - Barriers to procreational intentions among cancer survivors 2 years after
      diagnosis: a French national cross-sectional survey.
AB  - OBJECTIVES: To determine the procreational intention rates among cancer survivors
      whose fertility was unimpaired and to identify the factors associated with their
      procreational intentions. METHODS: Six thousand nine hundred and fifty-seven
      adult cancer patients treated between September and October 2002 were randomly
      selected from the French National Health Insurance Fund's Chronic Disease File.
      Of the 6957, 4270 responded to a cross-sectional questionnaire 2 years after
      diagnosis, of whom 959 reported being fertile and responded to a question about
      their procreational intentions. RESULTS: Among the 257 male and female survivors
      aged 20-44, 86 (33.5%) had procreational intentions. After adjusting for age,
      gender, and already having children, only a high educational level (adjusted odds
      ratio: 3.1, 95% confidence interval 1.3-7.8) and stable or increasing financial
      resources (2.4, 1.0-5.7) were independently associated with the respondents'
      procreational intentions. Neither cancer stage at diagnosis nor the present stage
      significantly affected their plans in this respect. CONCLUSIONS: Two years after
      cancer diagnosis, the reasons why some survivors who are still fertile have no
      parenthood projects were similar to those earlier given by members of the general
      population.

PMID- 20151411
TI  - Calculation of the standard binding free energy of sparsomycin to the ribosomal
      peptidyl-transferase P-site using molecular dynamics simulations with restraining
      potentials.
AB  - The standard (absolute) binding free energy of the antibiotic sparsomycin with
      the 50S bacteria ribosomal subunit is calculated using molecular dynamics (MD)
      free energy perturbation (FEP) simulations with restraining potentials developed
      by Wang et al. [Biophys. J. 91:2798-2814 (2006)]. In the simulation protocol,
      restraining potentials are activated for the orientational and translational
      movements of the ligand relative to the binding site when it is decoupled from
      the binding pocket, and then released once the ligand fully interacts with the
      rest of the system. A reduced system is simulated to decrease the computational
      cost of the FEP/MD calculations and the effects of the surrounding atoms are
      incorporated using the generalized solvent boundary potential (GSBP) method. The
      loss of conformational freedom of the ligand upon binding is characterized using
      the potential of mean force (PMF) as a function of the root-mean-square deviation
      (RMSD) relative to the bound conformation. The number of water molecules in the
      binding pocket is allowed to fluctuate dynamically in response to the ligand
      during the calculations by combining FEP/MD with grand canonical Monte Carlo
      (GCMC) simulations. The calculated binding free energy is about -6 kcal/mol,
      which is in reasonable agreement with the experimental value. The information
      gleaned from this study provides new insight on the recognition of ribosome by
      sparsomycin and highlights the challenges in calculations of absolute binding
      free energies in these systems.

PMID- 20151413
TI  - Role of sperm alphavbeta3 integrin in mouse fertilization.
AB  - Oocyte integrins have been described as essential for fertilization. But this
      concept has been challenged by deletion experiments. Recently, we have shown that
      sperm integrin alpha6beta1 plays a determinant role in mouse gamete interaction.
      In this study, we demonstrate the presence of alphavbeta3 integrin by Western
      blot and immunofluorescence on the sperm membrane. Oocytes and/or sperm
      preincubations with anti-alphav or anti-beta3 antibodies were performed before in
      vitro fertilization on cumulus-intact and zona-free egg assays. We observed
      inhibitory effects on the fusion process mostly by means of sperm function. An
      antibody directed against vitronectin inhibited gametes fusion, whereas the
      presence of exogenous vitronectin increased its efficiency. We suggest that
      vitronectin (on multimeric forms) can play a first nonspecific link corresponding
      to loosely bound spermatozoa to oocyte and that this link could be mediated by
      means of oocyte proteoglycans or integrins, and sperm alphavbeta3 integrin.

PMID- 20151415
TI  - Dynamical aspects of molecular recognition.

PMID- 20151416
TI  - Cataloging topologies of protein folding patterns.
AB  - Comparing and classifying protein folding patterns allows organizing the known
      structures, structure search and retrieval, and investigation of general
      principles of protein architecture. We have been developing a concise tableau
      representation of protein folding patterns, based on the order and contact
      patterns of elements of secondary structure: helices and strands of sheet (Lesk,
      1995; Kamat and Lesk, 2007; Konagurthu et al., 2008). The tableaux provide a
      database, derived from the world-wide protein data bank, mineable in studies of
      protein architecture, including: (i) determination of statistical properties of
      secondary structure contacts in an unbiased set of protein domains, (ii)
      investigations of the range of, and relationships among, protein topologies,
      (iii) investigation of the relationship between local structure of proteins and
      the complete folding topology, (iv) potential for fold identification from amino
      acid sequence, and (v) the basis for a complete enumeration of possible protein
      folding patterns, which can be compared with the corpus of known structures.

PMID- 20151418
TI  - Lipid transport and signaling in Caenorhabditis elegans.
AB  - The strengths of the Caenorhabditis elegans model have been recently applied to
      the study of the pathways of lipid storage, transport, and signaling. As the
      lipid storage field has recently been reviewed, in this minireview we (1) discuss
      some recent studies revealing important physiological roles for lipases in
      mobilizing lipid reserves, (2) describe various pathways of lipid transport, with
      a particular focus on the roles of lipoproteins, (3) debate the utility of using
      C. elegans as a model for human dyslipidemias that impinge on atherosclerosis,
      and (4) describe several systems where lipids affect signaling, highlighting the
      particular properties of lipids as information-carrying molecules. We conclude
      that the study of lipid biology in C. elegans exemplifies the advantages afforded
      by a whole-animal model system where interactions between tissues and organs, and
      functions such as nutrient absorption, distribution, and storage, as well as
      reproduction can all be studied simultaneously.

PMID- 20151417
TI  - MM-GBSA binding free energy decomposition and T cell receptor engineering.
AB  - Recognition by the T-cell receptor (TCR) of immunogenic peptides (p) presented by
      class I major histocompatibility complexes (MHC) is the key event in the immune
      response against virus infected cells or tumor cells. The major determinant of T
      cell activation is the affinity of the TCR for the peptide-MHC complex, though
      kinetic parameters are also important. A study of the 2C TCR/SIYR/H-2Kb system
      using a binding free energy decomposition (BFED) based on the MM-GBSA approach
      had been performed to assess the performance of the approach on this system. The
      results showed that the TCR-p-MHC BFED including entropic terms provides a
      detailed and reliable description of the energetics of the interaction (Zoete and
      Michielin, 2007). Based on these results, we have developed a new approach to
      design sequence modifications for a TCR recognizing the human leukocyte antigen
      (HLA)-A2 restricted tumor epitope NY-ESO-1. NY-ESO-1 is a cancer testis antigen
      expressed not only in melanoma, but also on several other types of cancers. It
      has been observed at high frequencies in melanoma patients with unusually
      positive clinical outcome and, therefore, represents an interesting target for
      adoptive transfer with modified TCR. Sequence modifications of TCR potentially
      increasing the affinity for this epitope have been proposed and tested in vitro.
      T cells expressing some of the proposed TCR mutants showed better T cell
      functionality, with improved killing of peptide-loaded T2 cells and better
      proliferative capacity compared to the wild type TCR expressing cells. These
      results open the door of rational TCR design for adoptive transfer cancer
      therapy.

PMID- 20151419
TI  - Differential gene expression in migrating cortical interneurons during mouse
      forebrain development.
AB  - Gamma-aminobutyric acid (GABA)ergic interneurons play a vital role in modulating
      the activity of the cerebral cortex, and disruptions to their function have been
      linked to neurological disorders such as schizophrenia and epilepsy. These cells
      originate in the ganglionic eminences (GE) of the ventral telencephalon and
      undergo tangential migration to enter the cortex. Currently, little is known
      about the signaling mechanisms that regulate interneuron migration. We therefore
      performed a microarray analysis comparing the changes in gene expression between
      the GABAergic interneurons that are actively migrating into the cortex with those
      in the GE. We were able to isolate pure populations of GABAergic cells by
      fluorescence-activated cell sorting of cortex and GE from embryonic brains of
      glutamate decarboxylase 67 (GAD67)-green fluorescent protein (GFP) transgenic
      mice. Our microarray analysis identified a number of novel genes that were
      upregulated in migrating cortical interneurons at both E13.5 and E15.5. Many of
      these genes have previously been shown to play a role in cell migration of both
      neuronal and non-neuronal cell types. In addition, several of the genes
      identified are involved in the regulation of migratory processes, such as neurite
      outgrowth, cell adhesion, and remodeling of the actin cytoskeleton and
      microtubule network. Moreover, quantitative polymerase chain reaction and in situ
      hybridization analyses confirmed that the expression of some of these genes is
      restricted to cortical interneurons. These data therefore provide a framework for
      future studies aimed at elucidating the complexities of interneuron migration
      and, in turn, may reveal important genes that are related to the development of
      specific neurological disorders.

PMID- 20151420
TI  - Is ionizing radiation responsible for the increasing incidence of thyroid cancer?

PMID- 20151421
TI  - Route of intracerebrospinal fluid chemotherapy administration and efficacy of
      therapy in neoplastic meningitis.
AB  - BACKGROUND: A study was undertaken to determine whether route (intraventricular
      vs intralumbar) of intracerebrospinal fluid (intra-CSF) drug administration
      influences progression-free survival in the treatment of patients with neoplastic
      meningitis, which occurs in 1% to 5% of patients with known cancer. Currently
      available treatment options result in modest responses, which is in part a
      reflection of obstacles to drug delivery into the leptomeningeal space. METHODS:
      One hundred patients with clinically and cytologically or radiographically
      documented neoplastic meningitis because of solid cancers received intra-CSF
      liposomal cytarabine or methotrexate as specified in a randomized phase 4 trial.
      The 2 treatment arms were well balanced for demographic and tumor-related
      characteristics of known prognostic importance, including age, performance
      status, tumor type, extent of systemic and other central nervous system (CNS)
      disease, prior CNS therapy, and concurrent systemic chemotherapy. RESULTS: One
      hundred patients were randomized and treated (52 with sustained-release
      cytarabine, and 48 with methotrexate). Progression-free survival (the primary
      study endpoint) was identical between the sustained-release cytarabine and
      methotrexate treatment arms for all 100 patients (35 vs 37.5 days, P = .79). When
      progression-free survival was examined as a function of route of chemotherapy
      administration (lumbar vs ventricular), there was no difference for patients
      treated with sustained-release cytarabine (29 vs 43 days, P = .35). For patients
      treated with methotrexate, however, there was a statistically significant
      difference favoring patients receiving intraventricular therapy (19 vs 43 days, P
      = .048). CONCLUSIONS: Site of intra-CSF chemotherapy drug administration is
      clinically relevant with short half-life drugs such as methotrexate.

PMID- 20151422
TI  - Accuracy and sensitivity of computed tomography-guided percutaneous needle biopsy
      of pulmonary hilar lymph nodes.
AB  - BACKGROUND: Because of their proximity to the pulmonary artery or vein, hilar
      lymph nodes are routinely biopsied with endobronchial or endoscopic
      ultrasonography (EUS)-guided fine-needle aspiration biopsy (FNAB). Computed
      tomography (CT)-guided percutaneous needle biopsy (PNB) allows the operator to
      acquire a larger core needle biopsy (CNB) when initial samples are inconclusive,
      when the suspected disease is not optimally diagnosed with FNAB, or when
      biomarkers are required. The purpose of this study was to retrospectively
      evaluate the sensitivity and accuracy of CT-guided PNB in patients with hilar
      adenopathy. METHODS: The authors identified 80 patients who underwent 81 CT
      guided PNBs of pulmonary hilar lesions from October 2002 through December 2006
      and retrospectively reviewed their medical and imaging records. The PNB
      sensitivity and accuracy were calculated in each case, and each case was reviewed
      for complications, including pneumothorax and subsequent thoracostomy tube
      insertion. RESULTS: PNB included FNAB and CNB in 81 (100%) and 14 (17%)
      procedures, respectively. Data on 69 PNB specimens (67 FNAB specimens and 13 CNB
      specimens) were available for statistical analysis. Overall, PNB had a
      sensitivity of 91.4% (95% confidence interval [CI], 81.0%-97.1%) and an accuracy
      rate of 92.8% (95% CI, 83.9%-97.1%). Pneumothoraxes occurred in 39 patients
      (48%), 26 (32%) of whom required thoracostomy tube insertion. CONCLUSIONS: CT
      guided PNB of pulmonary hilar lesions has high sensitivity and accuracy and
      represents a viable alternative for endobronchial ultrasound- or EUS-guided FNAB
      when larger biopsy samples are required for diagnosis or biomarker analysis.
      However, the procedure can result in high rates of pneumothorax.

PMID- 20151423
TI  - Nuclear grading of primary pulmonary adenocarcinomas: correlation between nuclear
      size and prognosis.
AB  - BACKGROUND: According to the World Health Organization Classification of Tumors,
      the prognostic value of morphometric cytologic atypia has not been assessed in
      pulmonary adenocarcinoma. METHODS: Primary tumors of 133 pulmonary
      adenocarcinomas <or=2 cm were analyzed using an image processor for analytical
      pathology. The results were evaluated using receiver operator characteristic
      curve analysis, and survival curves were drawn by the Kaplan-Meier method.
      Furthermore, the results were applied to routine histological diagnosis. Four
      pathologists evaluated the nuclear factors relative to the size of small
      lymphocytes as a standard. RESULTS: By using the nuclear area and nuclear major
      axis dimension, lung adenocarcinomas were divisible into 2 groups showing
      extremely favorable prognosis and fairly favorable prognosis, without considering
      histological features or classification. A nuclear area level of <67 microm(2)
      was correlated with longer survival (P < .0001), and the 5-year survival rate was
      90.4%. Similarly, a nuclear diameter level of <0.7 microm was correlated with
      longer survival (P = .0002), and the 5-year survival rate was 88.6%. The mean (+/
      standard deviation [SD]) value of the kappa statistic for the 4 pathologists who
      evaluated the cases using the size of small lymphocytes as a standard was 0.58 +/
      0.10, and the mean (+/-SD) value of the accuracy metric was 0.66 +/- 0.10.
      CONCLUSIONS: Nuclear area and nuclear major dimension are 2 useful independent
      markers for evaluating the prognosis of lung adenocarcinoma.

PMID- 20151424
TI  - Commentary on Effects of radiotherapy with concomitant and adjuvant temozolomide
      versus radiotherapy alone on survival in glioblastoma in a randomised phase III
      study: 5-year analysis of the EORTC-NCIC trial (Lancet Oncol. 2009;10:459-466).
AB  - Recently, un update of the important European Organization for Research and
      Treatment of Cancer study 26981 was published without correcting deficiencies
      that already were known and publicized in 2008. In the current commentary, the
      author specifies those issues to help prevent incorrect conclusions and discusses
      reasons why the journal that published the update dismissed a letter clarifying
      those shortcomings.

PMID- 20151425
TI  - Analysis of prognostic factors in Ewing sarcoma using a population-based cancer
      registry.
AB  - BACKGROUND: Ewing sarcoma is a high-grade malignancy that most often occurs in
      children. Because its occurrence in adults has been historically low, few studies
      have been published on the epidemiology of Ewing sarcoma in this group of
      patients. By using data from a large, population-based cancer registry, the
      authors designed the present study to examine the outcome of children and adult
      patients with Ewing sarcoma and relevant prognostic factors. METHODS: A
      retrospective analysis of Ewing sarcoma patient cases in the California Cancer
      Registry database was performed to identify incident patient cases diagnosed
      between 1989-2007. Comparisons were made to examine differences in demographics,
      disease characteristics, treatment, and survival. Survival analyses were
      performed using Kaplan-Meier method with log-rank tests and Cox proportional
      hazards models. RESULTS: Seven hundred and twenty-five incident patient cases of
      Ewing sarcoma were identified, including 372 (51.3%) children and 353 (48.7%)
      adults. Hispanic race was associated with young age (P = .001) and lower
      socioeconomic status (SES; P = .0001). Pelvic involvement was associated with
      large tumor size (>8 cm; P < .0001), an increased incidence of metastasis (P <
      .0002), and poorer survival (P < .0001). After adjusting for clinically relevant
      factors, statistically significant decreased overall survival was seen with
      adults (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.35-2.17),
      Hispanics (HR, 1.33; 95% CI, 1.01-1.75), metastatic disease (HR, 2.74; 95% CI,
      2.14-3.49), large tumor size (HR, 1.65; 95% CI, 1.17-2.34), no surgical
      treatment, and low SES. CONCLUSIONS: The authors determined that adult age,
      Hispanic race, metastatic disease, large tumor size, and low SES are poor
      prognostic factors for overall survival among Ewing sarcoma patient cases.

PMID- 20151427
TI  - Number of lymph nodes removed in sentinel lymph node-negative breast cancer
      patients is significantly related to patient age and tumor size: a new source of
      bias in morbidity assessment?
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy has been well-established for
      axillary lymph node staging for patients with breast cancer. For lymph node
      negative patients, planned "backup" axillary lymph node dissection (ALND) is
      rarely indicated. Among patients with negative SLNs, the authors observed
      variation by tumor size and patient age in the total number of lymph nodes
      removed (SLNs plus non-SLNs). They hypothesized that this variation is an
      unrecognized source of bias for studies examining the morbidity of SLN biopsy.
      METHODS: Retrospective review of this institution's SLN database identified 4103
      SLN biopsy procedures between 1997 and 2004 in which SLN biopsy was performed for
      prophylactic mastectomy, ductal carcinoma in situ, or T1 to T2 invasive cancers,
      and the SLNs were benign. RESULTS: The mean number of SLNs, non-SLNs, and total
      lymph nodes for all tumor sizes was 2.8, 1.5, and 4.3, respectively, and
      increased with tumor size (more lymph nodes were removed for T2 than for T1
      tumors: 6.3 vs 4.3; P < .0001). This trend remained significant even in the later
      years of these investigators' experience with SLN biopsy, and was observed for 5
      of 9 (56%) surgeons. More total lymph nodes were also removed in patients aged
      <or=50 years than in those aged >50 years (4.6 lymph nodes vs 4.2 lymph nodes; P
      = .006). In approximately 8% of patients (322 of 4103 patients), >or=10 lymph
      nodes were removed. CONCLUSIONS: The morbidity of SLN biopsy is less than that of
      ALND, but for pN0 patients, the total number of lymph nodes removed increased
      with tumor size and younger patient age. This variation is a previously
      unrecognized source of bias for studies that examine the morbidity of SLN biopsy.

PMID- 20151426
TI  - Fyn: a novel molecular target in cancer.
AB  - Fyn is 59-kDa member of the Src family of kinases that is historically associated
      with T-cell and neuronal signaling in development and normal cellular physiology.
      Whereas Src has been heavily studied in cancer, less attention has been
      traditionally awarded to the other Src kinases such as Fyn. Our group has shown
      that Fyn is particularly upregulated in prostate cancer in contrast to the
      alternative members of the Src family. This suggests that it may mediate several
      important processes attributed to Src kinases in prostate cancer and other
      malignancies. These functions include not only cellular growth and proliferation
      but also morphogenesis and cellular motility. Together, these suggest a role for
      Fyn in both progression and metastasis. As several agents in clinical development
      affect Fyn activation, understanding the role that Fyn plays in cancer is of
      great importance in oncology. Cancer 2010. (c) 2010 American Cancer Society.

PMID- 20151428
TI  - Increasing cytotechnologist workload above 100 slides per day using the ThinPrep
      imaging system leads to significant reductions in screening accuracy.
AB  - BACKGROUND: With the current and projected shortage of a cytotechnologist (CT)
      workforce and the desire to reduce laboratory costs, increased productivity with
      automated assisted primary screening has become an attractive option for many
      laboratories. To the best of the authors' knowledge, longitudinal studies
      examining the effect of increasing workload on the performance of individual CTs
      have not been performed previously. METHODS: Using the ThinPrep imaging system
      (TIS), the performance of 3 CTs with variable levels of experience were
      evaluated. Their productivity was noted to increase from an average of 87 to 118
      slides per day. The analysis included comparisons of error rates, screening
      rates, and screening times, including a review of 22 fields of view (FOV).
      Poststudy interviews of the CTs were also performed. RESULTS: Increased workload
      was found to be proportional to the decreased percentage of cases that underwent
      full manual review (25.2% to 20.1%; P < .001), and decreased actual screening
      times (7.3 hours/day to 6.7 hours/day, and 5.0 minutes/slide to 3.7
      minutes/slide). This resulted in a lower detection of total abnormal findings
      (10.4% to 8.3%; P < .001), atypical squamous cells (6.7% to 4.9%; P < .001), and
      high-grade squamous intraepithelial lesion (0.9 %to 0.7%; P = .37), as well as an
      increased false-negative fraction rate (3.8% to 7.0%; P = .08). CONCLUSIONS: The
      results of the current study indicate that an increased average CT workload >100
      slides per day with the TIS appears to have been accomplished mostly through a
      reduction in the amount of time spent reviewing the 22 FOV and the percentage of
      cases that underwent full manual review, which resulted in a significantly
      reduced screening performance.

PMID- 20151431
TI  - Genetic drift. Overview of German, Nazi, and Holocaust medicine.
AB  - An overview of German, Nazi, and Holocaust medicine brings together a group of
      subjects discussed separately elsewhere. Topics considered include German
      medicine before and during the Nazi era, such as advanced concepts in
      epidemiology, preventive medicine, public health policy, screening programs,
      occupational health laws, compensation for certain medical conditions, and two
      remarkable guidelines for informed consent for medical procedures; also
      considered are the Nuremberg Code; American models for early Nazi programs,
      including compulsory sterilization, abusive medical experiments on prison
      inmates, and discrimination against black people; two ironies in US and Nazi
      laws; social Darwinism and racial hygiene; complicity of Nazi physicians,
      including the acts of sterilization, human experimentation, and genocide; Nazi
      persecution of Jewish physicians; eponyms of unethical German physicians with
      particular emphasis on Reiter, Hallervorden, and Pernkopf; eponyms of famous
      physicians who were Nazi victims, including Pick and van Creveld; and finally, a
      recommendation for convening an international committee of physicians and
      ethicists to deal with five issues: (a) to propose alternative names for eponyms
      of physicians who exhibited complicity during the Nazi era; (b) to honor the
      eponyms and stories of physicians who were victims of Nazi atrocities and
      genocide; (c) to apply vigorous pressure to those German and Austrian Institutes
      that have not yet undertaken investigations to determine if the bodies of Nazi
      victims remain in their collections; (d) to recommend holding annual
      commemorations in medical schools and research institutes worldwide to remember
      and to reflect on the victims of compromised medical practice, particularly, but
      not exclusively, during the Nazi era because atrocities and acts of genocide have
      occurred elsewhere; and (e) to examine the influence of any political ideology
      that compromises the practice of medicine.

PMID- 20151432
TI  - Control of biocatalytic transformations by programmed DNA assemblies.
AB  - This study demonstrates the self-assembly of inhibitor/enzyme-tethered nucleic
      acid fragments or enzyme I-, enzyme II-modified nucleic acids into functional
      nanostructures that lead to the controlled inhibition of the enzyme or the
      activation of an enzyme cascade. In one system, the anti-cocaine aptamer subunits
      are modified with monocarboxy methylene blue (MB(+)) as the inhibitor and with
      choline oxidase (ChOx). The cocaine-induced self-assembly of the aptamer subunits
      complex results in the inhibition of ChOx by MB(+). In a further configuration,
      two nucleic acids of limited complementarity are functionalized at their 3' and
      5' ends with glucose oxidase (GOx) and horseradish peroxidase (HRP),
      respectively, or with MB(+) and ChOx. In the presence of a target DNA sequence,
      synergistic complementary base-pairing occurs, thus leading to stable
      supramolecular Y-shaped nanostructures of the nucleic acid units. A GOx/HRP
      bienzyme cascade or the programmed inhibition of ChOx by MB(+) is demonstrated in
      the resulting nucleic acid nanostructures. A quantitative theoretical model that
      describes the nucleic acid assemblies and that results in the inhibition of ChOx
      by MB(+) or in the activation of the GOx/HRP cascade, respectively, is provided.

PMID- 20151429
TI  - Azacitidine for the treatment of lower risk myelodysplastic syndromes : a
      retrospective study of 74 patients enrolled in an Italian named patient program.
AB  - BACKGROUND: Azacitidine induces responses and prolongs overall survival compared
      with conventional care regimens in patients who have high-risk myelodysplastic
      syndromes (MDS). However, limited data are available concerning the efficacy and
      safety of azacitidine in patients who have lower risk MDS. METHODS: The authors
      retrospectively evaluated 74 patients with International Prognostic Scoring
      System low-risk or intermediate 1-risk MDS, who received azacitidine on a
      national named patient program. At baseline, 84% of patients were transfusion
      dependent, 57% had received erythropoietin, and 51% were aged >70 years.
      Azacitidine was administered subcutaneously for 5 days (n = 29 patients), 7 days
      (n = 43 patients), or 10 days (n = 2 patients) every month at a dose of 75
      mg/m(2) daily (n = 45 patients) or at a fixed dose of 100 mg daily (n = 29
      patients) and for a median of 7 cycles (range, 1-30 cycles). RESULTS: According
      to the 2006 International Working Group criteria, overall response rate (ORR) was
      45.9%, including complete responses (10.8%), partial responses (9.5%),
      hematologic improvements (20.3%), and bone marrow complete responses (5.4%). The
      ORR was 51.6% in 64 patients who completed > or = 4 cycles of treatment. The
      median duration of response was 6 months (range, 1-30 months). After a median
      follow-up of 15 months, 71% of patients remained alive. A survival benefit was
      observed in responders versus nonresponders (94% vs 54% of patients projected to
      be alive at 2.5 years, respectively; P < .0014). The most common grade 3 or 4
      adverse events were myelosuppression (21.6%) and infection (6.8%). CONCLUSIONS:
      The current results indicated that azacitidine may be a feasible and effective
      treatment for patients with lower risk MDS.

PMID- 20151433
TI  - A reversible dual-response fluorescence switch for the detection of multiple
      analytes.
AB  - This paper reports a reversible dual fluorescence switch for the detection of a
      proton target and 2,4,6-trinitrotoluene (TNT) with opposite-response results,
      based on fluorophore derivatization of silica nanoparticles. Fluorescent silica
      nanoparticles were synthesized through modification of the surface with a
      nitrobenzoxadiazole (NBD) fluorophore and an organic amine to form a hybrid
      monolayer of fluorophores and amino ligands; the resultant nanoparticles showed
      different fluorescence responses to the proton target and TNT. Protonation of the
      amino ligands leads to fluorescence enhancement due to inhibition of photoinduced
      electron transfer (PET) between the amine and fluorophore. By contrast, addition
      of TNT results in fluorescence quenching because a fluorescence resonance energy
      transfer (FRET) happens between the NBD fluorophore and the formed TNT-amine
      complex. The fluorescence signal is reversible through washing with the proper
      solvents and the nanoparticles can be reused after centrifugal separation.
      Furthermore, these nanoparticles were assembled into chips on an etched silicon
      wafer for the detection of TNT and the proton target. The assembled chip can be
      used as a convenient indicator of herbicide (2,4-dichlorophenoxyacetic acid) and
      TNT residues with the use of only 10 microL of sample. The simple NBD-grafted
      silica nanoparticles reported here show a reversible signal and good assembly
      flexibility; thus, they can be applied in multianalyte detection.

PMID- 20151435
TI  - Specific identification and quantification of the spoilage microorganism
      Brettanomyces in wine by flow cytometry: a useful tool for winemakers.

PMID- 20151434
TI  - The effects of detergents on the polymerization properties of actin.
AB  - Effects of some detergents-most frequently used in membrane raft studies-on the
      polymerization properties of actin were examined under in vitro and in vivo
      conditions, for protein and cellular investigations, respectively. Under in vitro
      conditions the polymerization rates were measured with pyrene-labeled actin. We
      found that polymerization rate depended on the detergent concentration by
      following either biphasic characteristics or only decreasing tendency. The
      strongest effects were observed at relatively low detergent concentrations. SDS
      PAGE electrophoresis and dynamic light-scattering measurements provided further
      evidences for the size distribution of actin filaments formed under the influence
      of detergents. Comparing the polymerization rates measured in the presence of
      different detergents to those obtained with various magnesium and KCl
      concentrations showed that detergents may influence the actin polymerization at
      three levels by modifying: (i) the monomer-monomer interaction, (ii) the local
      ionic strength, and (iii) the affinity of actin for various cations. In vivo
      studies on NIH 3T3MDR1 cells using TRITC-phalloidin detected fast
      depolymerization of large extent around the critical micellar concentrations of
      the detergents. We concluded that microdomain insolubility observed in the
      presence of detergents is hardly to be the result of the stabilization of the
      submembrane actin cytoskeleton merely; rather inter-lipid and lipid-protein
      interactions are also involved within the detergent-resistant membranes.

PMID- 20151436
TI  - Three-dimensional antiferromagnetic order of single-chain magnets: a new approach
      to design molecule-based magnets.
AB  - Two one-dimensional compounds composed of a 1:1 ratio of Mn(III) salen-type
      complex and Ni(II) oximato moiety with different counter anions, PF(6)(-) and
      BPh(4)(-), were synthesized: [Mn(3,5-Cl(2)saltmen)Ni(pao)(2)(phen)]PF(6) (1) and
      [Mn(5-Clsaltmen)Ni(pao)(2)(phen)]BPh(4) (2), where 3,5-Cl(2)saltmen(2-) = N,N'
      (1,1,2,2-tetramethylethylene)bis(3,5-dichlorosalicylideneiminate); 5-Clsaltmen(2
      ) = N,N'-(1,1,2,2-tetramethylethylene)bis(5-chlorosalicylideneiminate); pao(-) =
      pyridine-2-aldoximate; and phen = 1,10-phenanthroline. Single-crystal X-ray
      diffraction study was carried out for both compounds. In 1 and 2, the chain
      topology is very similar forming an alternating linear chain with a [-Mn(III)-ON
      Ni(II)-NO-] repeating motif (where -ON- is the oximate bridge). The use of a
      bulky counteranion, such as BPh(4)(-), located between the chains in 2 rather
      than PF(6)(-) in 1, successfully led to the magnetic isolation of the chains in
      2. This minimization of the interchain interactions allows the study of the
      intrinsic magnetic properties of the chains present in 1 and 2. While 1 and 2
      possess, as expected, very similar paramagnetic properties above 15 K, their
      ground state is antiferromagnetic below 9.4 K and paramagnetic down to 1.8 K,
      respectively. Nevertheless, both compounds exhibit a magnet-type behavior at
      temperatures below 6 K. While for 2, the observed magnetism is well explained by
      a Single-Chain Magnet (SCM) behavior, the magnet properties for 1 are induced by
      the presence in the material of SCM building units that order
      antiferromagnetically. By controlling both intra- and interchain magnetic
      interactions in this new [Mn(III)Ni(II)] SCM system, a remarkable AF phase with a
      magnet-type behavior has been stabilized in relation with the intrinsic SCM
      properties of the chains present in 1. This result suggests that the simultaneous
      enhancement of both intrachain (J) and interchain (J') magnetic interactions
      (with keeping J >> J'), independently of the presence of AF phase might be an
      efficient route to design high temperature SCM-based magnets.

PMID- 20151437
TI  - Water--more than just a green solvent: a stereoselective one-pot access to all
      chiral tetrahydronaphthalenes in aqueous media.
AB  - A facile and highly stereoselective construction of heavily functionalized chiral
      tetrahydronaphthalene skeletons fused with an oxazolidine moiety has been
      developed. The process involves an organocatalytic tandem Michael/nitrone
      formation/intramolecular [3+2] nitrone-olefin cycloaddition in aqueous media.
      Using rationally designed substrates, the reaction conditions have been optimized
      and the one-pot process has been applied to a series of nitroolefin acrylates and
      aldehydes. The N-hydroxyphenylamine component used in the second step has also
      been varied. The stereochemistry of one product has been verified by an X-ray
      crystal structure determination. The water used in the strategy not only
      constitutes an environmentally benign solvent, but also helps to improve the
      reactivity and stereoselectivity.

PMID- 20151438
TI  - Transcription of chirality in the organogel systems dictates the
      enantiodifferentiating photodimerization of substituted anthracene.
AB  - An organogelator (G) that contains 2-anthracenecarboxylic acid (2Ac) attached
      covalently to a gelator counterpart that consists of 3,4,5-tris(n-dodecan-1
      yloxy)benzoic acid by means of a chiral amino alcohol linkage has been
      synthesized. G acts as an efficient gelator of organic solvents, including mixed
      solvents and chiral solvents. Photodimers isolated after the photoreaction of the
      gel samples display different degrees of stereoselectivity. In the gel state, the
      formation of head-to-head (h-h) photodimers is always favored over head-to-tail
      (h-t) photodimers. Enantiomeric excess (ee) values of the major h-h photodimers
      reached as high as -56% in the case of the gels with enantiomeric glycidyl methyl
      ethers. Here, the solvent chirality is outweighed by the intrinsic chirality of
      the gelator molecule. The packing of the chromophore in the gel state has been
      characterized by the absorption and the emission behaviors and their variations
      during the course of gel-to-sol phase transition. Whereas for the hexane gel,
      emission intensity increases with an increase in temperature, other systems show
      a decrease in emission intensity. Redshift of the lambda(max) in the gel spectra
      indicates the J-aggregate arrangement of the chromophores. Chiral transcription
      in the gel state has been investigated by CD spectroscopy, which shows a decrease
      in CD intensity during the gel-to-sol phase transition. The X-ray diffraction
      study clearly differentiates among the gels in terms of the order of molecular
      arrangements. The gel systems are categorized as strong, moderately strong, and
      weak, that originate from the cooperative or individual participations of
      intermolecular hydrogen-bonding and pi-pi interactions, fine-tuned by the solvent
      polarity and the gelation temperature. A simple model based on the experimental
      findings and the molecular preorientation as evidenced by the stereochemistry of
      the photodimers has been proposed.

PMID- 20151439
TI  - Energetic salts based on monoanions of N,N-bis(1H-tetrazol-5-yl)amine and 5,5'
      bis(tetrazole).
AB  - High-density energetic salts that contain nitrogen-rich cations and the 5
      (tetrazol-5-ylamino)tetrazolate (HBTA(-)) or the 5-(tetrazol-5-yl)tetrazolate
      (HBT(-)) anion were readily synthesized by the metathesis reactions of sulfate
      salts with barium compounds, such as bis[5-(tetrazol-5-ylamino)tetrazolate]
      (Ba(HBTA)(2)), barium iminobis(5-tetrazolate) (BaBTA), or barium 5,5'
      bis(tetrazolate) (BaBT) in aqueous solution. All salts were fully characterized
      by IR spectroscopy, multinuclear ((1)H, (13)C, (15)N) NMR spectroscopy, elemental
      analyses, density, differential scanning calorimetry (DSC), and impact
      sensitivity. Ba(HBTA)(2) x 4 H(2)O crystallizes in the triclinic space group P1,
      as determined by single-crystal X-ray diffraction, with a density of 2.177 g cm(
      3). The densities of the other organic energetic salts range between 1.55 and
      1.75 g cm(-3) as measured by a gas pycnometer. The detonation pressure (P) values
      calculated for these salts range from 19.4 to 33.6 GPa, and the detonation
      velocities (nu(D)) range from 7677 to 9487 m s(-1), which make them competitive
      energetic materials. Solid-state (13)C NMR spectroscopy was used as an effective
      technique to determine the structure of the products that were obtained from the
      metathesis reactions of biguanidinium sulfate with barium iminobis(5-tetrazolate)
      (BaBTA). Thus, the structure was determined as an HBTA salt by the comparison of
      its solid-state (13)C NMR spectroscopy with those of ammonium 5-(tetrazol-5
      ylamino)tetrazolate (AHBTA) and diammonium iminobis(5-tetrazolate) (A(2)BTA).

PMID- 20151440
TI  - Stereoselective triplet-sensitised radical reactions of furanone derivatives.
AB  - The stereo- and regioselectivity of triplet-sensitised radical reactions of
      furanone derivatives have been investigated. Furanones 7a,b were excited to the
      (3)pipi* state by triplet energy transfer from acetone. Intramolecular hydrogen
      abstraction then occurred such that hydrogen was transferred from the
      tetrahydropyran to the beta position of the furanone moiety. Radical combination
      of the tetrahydropyranyl and the oxoallyl radicals led to the final products
      8a,b. In the intramolecular reaction, overall, a pyranyl group adds to the alpha
      position of the furanone. The effect of conformation was first investigated with
      compounds 9a,b carrying an additional substituent on the tether between the
      furanone and pyranyl moiety. Further information on the effect of conformation
      and the relative configuration at the pyranyl anomeric centre and the furanone
      moiety was obtained from the transformations of the glucose derivatives 12, 14,
      17 and 18. Radical abstraction occurred at the anomeric centre and at the 5'
      position of the glucosyl moiety. Computational studies of the hydrogen
      abstraction step were carried out with model structures. The activation barriers
      of this step for different stereoisomers and the abstraction at the anomeric
      centre and at the 6'-position of the tetrahydropyranyl moiety were calculated.
      The results of this investigation are in accordance with experimental
      observations. Furthermore, they reveal that the reactivity and regioselectivity
      are mainly determined in the hydrogen-abstraction step. Intramolecular hydrogen
      abstraction (almost simultaneous electron and proton transfer) in (3)pipi*
      excited furanones only takes place under restricted structural conditions in a
      limited number of conformations that are defined by the relative configuration of
      the substrates. It is observed that in the biradical intermediate, back-hydrogen
      transfer occurs leading to the starting compound. In the case of glucose
      derivatives, this reaction led to epimerisation at the anomeric centre.

PMID- 20151441
TI  - Poly(ethylene glycol)-graft-hollow silica vesicles for drug delivery.

PMID- 20151442
TI  - A three-component reaction based on a remote-group-directed dynamic kinetic aza
      Michael addition: stereoselective synthesis of imidazolidin-4-ones.

PMID- 20151443
TI  - Endovenous laser therapy--application studies and latest investigations.
AB  - Endovenous laser therapy (ELT) was introduced in clinical practice as a therapy
      for incompetent veins about ten years ago. One characteristic of ELT is the broad
      spectrum of different treatment protocols by means of a variety of laser systems
      as well as manifold application forms and dosimetry concepts are under
      investigations. Clinical results with effective, relatively pain-free occlusion
      of incompetent varicosis veins have been observed, as well as undesired side
      effects such as ecchymosis, phlebitis and recanalization. In recent years
      systematic experimental investigations and the analysis of clinical results have
      increased the understanding of the interrelation between the clinical and
      physical aspects, followed to a continuous optimization of ELT. The use of IR
      wavelengths and radial irradiation concepts, together with continuous moving of
      the optical fiber seem to reduce possible side effects. This way ELT treatment
      becomes a more standardized effective method for the treatment of varicose veins.
      In future controlled randomized studies are required to compare optimized ELT
      treatment with other endoluminal modalities as well as conventional surgery.

PMID- 20151444
TI  - Stretching single DNA molecules to demonstrate high-force capabilities of
      holographic optical tweezers.
AB  - The well calibrated force-extension behaviour of single double-stranded DNA
      molecules was used as a standard to investigate the performance of phase-only
      holographic optical tweezers at high forces. Specifically, the characteristic
      overstretch transition at 65 pN was found to appear where expected, demonstrating
      (1) that holographic optical trap calibration using thermal fluctuation methods
      is valid to high forces; (2) that the holographic optical traps are harmonic out
      to >250 nm of 2.1 mum particle displacement; and (3) that temporal modulations in
      traps induced by the spatial light modulator (SLM) do not affect the ability of
      optical traps to hold and steer particles against high forces. These studies
      demonstrate a new high-force capability for holographic optical traps achievable
      by SLM technologies.

PMID- 20151445
TI  - An antibody-based affinity chromatography tool to assess Cu, Zn superoxide
      dismutase (SOD) G93A structural complexity in vivo.
AB  - 'Conformational diseases' are a group of diverse disorders that have been
      associated with misfolding of specific proteins, leading to their aggregation in
      particular cell tissues. Despite their relevance, the mechanisms involved in
      neurodegenerative processes remains poorly understood. Mutations in Cu,Zn
      superoxide dismutase (SOD1) are implicated in death of motor neurons in
      amyotrophic lateral sclerosis. Among others, the SOD1(G93A) mutation is known to
      weaken the structure and this could lead to conformational variations of the
      protein. As an approach to understand the tissue-specific propensity of protein
      aggregation, we developed an experimental procedure allowing rapid extraction of
      variants of human SOD1 (hSOD1) produced in different tissues. Using an antibody
      based affinity chromatography procedure enzymatically active hSOD was extracted,
      indicating preservation of its native conformation. Analysis of the eluted
      fractions of hSOD extracted from the brain and liver of transgenic hSOD(G93A)
      rats provided evidence about heterodimers rSOD-hSOD(G93A) formation in both
      extracts. Moreover, when characterized by 2-DE and MALDI-TOF/TOF MS, the
      extracted hSOD(G93A) showed a complex profile suggesting the existence of various
      covalent modifications of the enzyme in both tissues. Thus, this method should
      allow following post-translational modifications of hSOD1 produced in various
      tissues.

PMID- 20151447
TI  - Transgenic crops and plant biotechnology.

PMID- 20151451
TI  - Biotech round the world: Ecuador's oil versus GMO ban?

PMID- 20151446
TI  - Systems metabolic engineering: genome-scale models and beyond.
AB  - The advent of high throughput genome-scale bioinformatics has led to an
      exponential increase in available cellular system data. Systems metabolic
      engineering attempts to use data-driven approaches--based on the data collected
      with high throughput technologies--to identify gene targets and optimize
      phenotypical properties on a systems level. Current systems metabolic engineering
      tools are limited for predicting and defining complex phenotypes such as chemical
      tolerances and other global, multigenic traits. The most pragmatic systems-based
      tool for metabolic engineering to arise is the in silico genome-scale metabolic
      reconstruction. This tool has seen wide adoption for modeling cell growth and
      predicting beneficial gene knockouts, and we examine here how this approach can
      be expanded for novel organisms. This review will highlight advances of the
      systems metabolic engineering approach with a focus on de novo development and
      use of genome-scale metabolic reconstructions for metabolic engineering
      applications. We will then discuss the challenges and prospects for this emerging
      field to enable model-based metabolic engineering. Specifically, we argue that
      current state-of-the-art systems metabolic engineering techniques represent a
      viable first step for improving product yield that still must be followed by
      combinatorial techniques or random strain mutagenesis to achieve optimal cellular
      systems.

PMID- 20151452
TI  - NorthernLights in slide-based cytometry and microscopy.
AB  - In recent years, slide-based cytometry has become a key technology for
      polychromatic cytometric investigations, and many efforts have been made to
      increase the number of measurable fluorochromes for multiparametric analysis.
      Sequential photobleaching of fluorochromes next to very photostable dyes is one
      approach for this technology. As the ALEXA dyes are known to be photostable as
      compared to the conventional fluorochromes FITC, PE (Riggs et al., Am J Pathol
      1958;34:1081-1097), and APC, a differentiation within a fluorochrome pair is
      possible. Here, we have analyzed the newly available NorthernLights secondary
      antibodies for use in slide-based cytometry and microscopy. Currently, these
      fluorochrome-conjugates are now available with three distinct excitation- and
      emission maxima (NL493, NL557, NL637). Their spectral properties are similar to
      the frequently used fluorochromes FITC, PE, and APC and can, therefore, be used
      with most common excitation sources of cytometers or microscopes. As the
      NorthernLights are bright, resistant to photobleaching, stable in alcohols and
      xylene and of affordable price, these dyes are promising candidates for use with
      most laser- and HBO/XBA-based fluorescence microscopy-like techniques.

PMID- 20151453
TI  - Recognition of Naegleriae ameba surface protein epitopes by anti-human CD45
      antibodies.
AB  - Phagocytosis is a highly conserved mechanism exhibited by both free-living amebas
      and mammalian blood cells. Similarities demonstrated by either cell type during
      engulfment of the same bacterial species may imply analogous surface proteins
      involved in receptor-mediated endocytosis. The increased availability of anti
      human leukocyte antibodies or clusters of differentiation (CD) markers used in
      conjunction with flow cytometric (FCM) and/or immunohistochemical (IHC) analysis
      provides investigators with a relatively easy method to screen different cell
      populations for comparable plasma membrane proteins. In this study, we incubated
      Naegleria and Acanthamoeba amebas with several directly conjugated anti-human
      leukocyte monoclonal antibodies (mAb) for similarly recognized amebic epitopes.
      CD marker selection was based upon a recognized role of each mAb in phagocyte
      activation and/or uptake of bacteria. These included CD14, CD45, and CD206. In
      FCM, only one CD45 antibody demonstrated strong reactivity with both Naegleria
      fowleri and Naegleria gruberi that was not expressed in similarly tested
      Acanthamoeba species. Additional testing of N. gruberi by IHC demonstrated
      reactivity to a different CD45 antibody. Our results suggest a possible utility
      of using anti-human leukocyte antibodies to screen amebic cells for similarly
      expressed protein epitopes. In doing so, several important items must be
      considered when selecting potential mAbs for testing to increase the probability
      of a positive result.

PMID- 20151455
TI  - Multichromatic phenotyping of HER receptor coexpression in breast tumor tissue
      samples using flow cytometry--possibilities and limitations.
AB  - The prognostic significance of HER2 expression in human breast carcinomas is
      beyond dispute nowadays. The HER family of receptor tyrosine kinases comprises
      four members (HER1/ErbB1/EGFR, HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4) that act
      in concert via transactivation and consequently compose a functional signaling
      unit. Besides HER2 overexpression, coexpression of other HER receptors has
      substantial impact on course of disease and potential therapeutic benefit. This
      observation is substantiated by numerous preclinical studies and retrospective
      studies done on patients with breast cancer. Against this background, the
      quantification of all HER receptor expressions at the same time would
      significantly extend the information content revealed by routine diagnosis of
      breast cancer tissues. Moreover, the knowledge of HER receptor coexpression
      profiles in primary tumor samples could provide the basis to design and develop
      highly specific antireceptor treatment strategies. Here, we report on a
      simultaneous flow cytometric detection of all four HER receptors on carcinoma
      cells isolated from primary breast cancer tissues and separated from
      nonepithelial cells by cytokeratin staining. Combined with DNA, i.e. ploidy
      quantification, the approach resulted in a six-parameter assay that could
      complement the diagnosis of a variety of diseases in which HER receptor
      expression has a pivotal impact on the degree of malignancy.

PMID- 20151456
TI  - N-acetylcysteine impairs survival of luteal cells through mitochondrial
      dysfunction.
AB  - N-acetylcysteine (NAC) is known as an antioxidant and used for mucus viscosity
      reduction. However, this drug prevents or induces cell death depending on the
      cell type. The response of steroidogenic luteal cells to NAC is unknown. Our data
      shows that NAC can behave as an antioxidant or prooxidant in dependency on the
      concentration and mitochondrial energization. NAC elevated the flowcytometric
      measured portion of hypodiploid (dying) cells. This rise was completely abolished
      by aurintricarboxylic acid, an inhibitor of topoisomerase II. NAC increased the
      secretion of nitric oxide and cellular nitrotyrosine. An image analysis indicated
      that cells pretreated with NAC and loaded with DHR showed a fluorescent structure
      probably elicited by the oxidative product of DHR, rhodamine 123 that sequesters
      mitochondrially. Pretreating luteal cells with NAC or adding NAC directly to
      mitochondrial fractions followed by assessing the mitochondrial transmembrane
      potential difference (Deltapsi) by the JC-1 technique demonstrated a marked
      decrease in Deltapsi. A protonophore restored Deltapsi and rotenone (an inhibitor
      of respiratory chain complex I) inhibited mitochondrial recovering. Thus, in
      steroidogenic luteal cells from healthy mature corpus luteum, NAC impairs
      cellular survival by interfering with mitochondrial metabolism. The protonophore
      induced recovering of NAC-provoked decrease in Deltapsi indicates that an ATP
      synthase-favored route of H(+) re-entry to the matrix is essentially switched off
      by NAC while other respiratory chain complexes remain intact. These data may be
      important for therapeutic timing of treatments with NAC. (c) 2010 International
      Society for Advancement of Cytometry.

PMID- 20151457
TI  - Plant-insect interactions: what can we learn from plant lectins?
AB  - Many plant lectins have high anti-insect potential. Although the effects of most
      lectins are only moderately influencing development or population growth of the
      insect, some lectins have strong insecticidal properties. In addition, some
      studies report a deterrent activity towards feeding and oviposition behavior.
      Transmission of plant lectins to the next trophic level has been investigated for
      several tritrophic interactions. Effects of lectins with different sugar
      specificities can vary substantially with the insect species under investigation
      and with the experimental setup. Lectin binding in the insect is an essential
      step in exerting a toxic effect. Attempts have been made to study the
      interactions of lectins in several insect tissues and to identify lectin-binding
      receptors. Ingested lectins generally bind to parts of the insect gut.
      Furthermore, some lectins such as the Galanthus nivalus agglutinin (GNA) cross
      the gut epithelium into the hemolymph and other tissues. Recently, several
      candidate lectin-binding receptors have been isolated from midgut extracts. To
      date little is known about the exact mechanism for insecticidal activity of plant
      lectins. However, insect glycobiology is an emerging research field and the
      recent technological advances in the analysis of lectin carbohydrate
      specificities and insect glycobiology will certainly lead to new insights in the
      interactions between plant lectins and insects, and to a better understanding of
      the molecular mechanisms involved.

PMID- 20151458
TI  - Pharmacology and placental transfer of a human alphav integrin monoclonal
      antibody in rabbits.
AB  - BACKGROUND: Intetumumab is a human IgG1 anti-alphav-integrin monoclonal antibody
      that inhibits angiogenesis. Integrin binding and angiogenesis are important in
      reproduction including fertilization, implantation, and embryofetal development.
      These studies were designed to determine the pharmacological relevance of the
      rabbit for the evaluation of potential effects on embryofetal development and to
      evaluate the placental transfer of intetumumab in rabbits. METHODS: In vitro
      pharmacology studies evaluated the binding of intetumumab to rabbit cells and the
      inhibition of vessel sprouting from rabbit aorta. For the evaluation of placental
      transfer, pregnant rabbits (8/group) were injected intravenously with intetumumab
      50 or 100 mg/kg every 2 days from Gestation Day (GD)7 to GD19. Maternal sera,
      fetal homogenates/sera, and amniotic fluid were collected at necropsy on GD19 or
      GD28 for evaluation of intetumumab concentrations. Clinical condition of the dams
      was monitored and fetuses were screened for abnormalities. RESULTS: Intetumumab
      (5-40 microg/mL) inhibited aortic cell adhesion to vitronectin and vessel
      sprouting from rabbit aortic rings. Immunohistochemical staining of rabbit
      tissues demonstrated binding of intetumumab to placenta. Administration of
      intetumumab to pregnant rabbits was well tolerated by the dams and the fetuses
      did not show major abnormalities. Fetal exposure to intetumumab relative to
      maternal exposure was <0.1% on GD19 and 100-130% on GD29. CONCLUSIONS: The rabbit
      is a pharmacologically relevant species for evaluation of potential developmental
      effects of intetumumab. Intetumumab crosses the rabbit placenta during the fetal
      period (GD 19-28).

PMID- 20151459
TI  - Injectable hyaluronic acid-dextran hydrogels and effects of implantation in
      ferret vocal fold.
AB  - Injectable hydrogels may potentially be used for augmentation/regeneration of the
      lamina propria of vocal fold tissue. In this study, hyaluronic acid (HA) and
      dextran were chemically modified and subsequently crosslinked via formation of
      hydrazone bonds in phosphate buffer. Swelling ratios, degradation, and
      compressive moduli of the resulting hydrogels were investigated. It was found
      that the properties of HA-dextran hydrogels were variable and the trend of
      variation could be correlated with the hydrogel composition. The biocompatibility
      of three injectable HA-dextran hydrogels with different crosslinking density was
      assessed in the vocal fold region using a ferret model. It was found that HA
      dextran hydrogels implanted for three weeks stimulated mild foreign-body
      reactions. Distinct tissue-material interactions were also observed for hydrogels
      made from different formulations: the hydrogel with the lowest crosslinking
      density was completely degraded in vivo; while material residues were visible for
      other types of hydrogel injections, with or without cell penetration into the
      implantation depending on the hydrogel composition. The in vivo results suggest
      that the HA-dextran hydrogel matrices can be further developed for applications
      of vocal fold tissue restoration.

PMID- 20151460
TI  - Entropy-supported marker selection and Mantel statistics for haplotype sharing
      analysis.
AB  - Haplotype sharing analysis is a well-established option for the investigation of
      the etiology of complex diseases. The statistical power of haplotype association
      methods depends strongly on how the information of unobserved haplotypes can be
      captured by multilocus genotypes. In this study we combine an entropy-based
      marker selection algorithm (EMS), with a haplotype sharing-based Mantel
      statistics into a new algorithm. Genetic markers are iteratively selected by
      their multilocus linkage disequilibrium (LD), which is assessed by a normalized
      entropy difference. The initial marker set is gradually enlarged to increase the
      available information on the amount of sharing around a potential susceptibility
      marker. Markers are rejected from joint phasing if they do not increase the
      multilocus LD. In simulated candidate gene studies, the Mantel statistics
      combined with the new EMS performs as well or better at detecting the disease
      single nucleotide polymorphism-or in indirect association analysis its flanking
      markers-than the Mantel statistics without selection of markers prior to
      haplotype estimation and the Mantel statistics using sliding windows of size
      five. It is therefore appealing to apply our selection approach for haplotype
      based association analysis, since marker selection driven by the observed data
      avoids both the arbitrary choice of markers when using a fixed window size, as
      well as the estimation of haplotype block structure.

PMID- 20151461
TI  - The proto-oncogene BCL6 promotes survival of olfactory sensory neurons.
AB  - For the mammalian olfactory epithelium to continually detect odorant, neuronal
      survival, apoptosis, and regeneration must be coordinated. Here, we showed that
      the proto-oncogene BCL6, which encodes a transcriptional repressor required for
      lymphocyte terminal differentiation, contributes to the survival of olfactory
      sensory neurons (OSNs). In the olfactory epithelia of the BCL6 null mutant mice,
      many OSNs were positive for both OMP and GAP43. The epithelium was relatively
      thinner, showing many apoptotic signals. These characters were phenotypically
      similar to those of the wild-type mice treated with nasal lectin irrigation,
      which acutely induces apoptosis of OSNs. Odorant receptors were expressed
      normally in the epithelia of the mutant mice, and their overall expression
      profile based on DNA microarray analyses was roughly similar to that of the
      apoptosis-induced olfactory epithelia of the wild-type mice. Experimental
      increase of BCL6 together with green fluorescent protein in OSNs using adenovirus
      mediated gene transfer made the epifluorescence last longer than the control
      fluorescence without exogenous BCL6 after the nasal lectin irrigation, indicating
      that BCL6 made the infected neurons survive longer. We conclude that BCL6 plays
      an active role in the survival of OSNs as an anti-apoptotic factor and confers
      immature OSNs enough time to fully differentiate into mature ones.

PMID- 20151462
TI  - Induction of myogenic differentiation by SDF-1 via CXCR4 and CXCR7 receptors.
AB  - The stromal cell-derived factor (SDF)-1/CXC receptor 4 (CXCR4) axis has been
      shown to play a role in skeletal muscle development, but its contribution to
      postnatal myogenesis and the role of the alternate SDF-1 receptor, CXC receptor 7
      (CXCR7), are poorly characterized. Western blot analysis and real-time polymerase
      chain reaction (PCR) were performed to evaluate in vitro the effect of SDF-1 and
      CXCR4 and CXCR7 inhibition on myogenic differentiation. Proliferating myoblasts
      express CXCR4, CXCR7, and SDF-1; during myogenic differentiation, CXCR4 and CXCR7
      levels are downregulated, and SDF-1 release is decreased. SDF-1 anticipates
      myosin heavy chain accumulation and myotube formation in both C2C12 myoblasts and
      satellite cells. Interestingly, inhibition of CXCR4 and CXCR7 signaling, either
      by drugs or RNA interfererence, blocks myogenic differentiation. Further, the
      CXCR4 antagonist, 4F-benzoyl-TN14003, inhibits myoblast cell cycle withdrawal and
      decreases the retinoblastoma gene (pRb) product accumulation in its
      hypophosphorylated form. Our experiments demonstrate that SDF-1 regulates
      myogenic differentiation via both CXCR4 and CXCR7 chemokine receptors.

PMID- 20151463
TI  - Myopathy and parkinsonism in phosphoglycerate kinase deficiency.
AB  - A 25-year-old man with exertional myoglobinuria had no evidence of hemolytic
      anemia, but he had severe parkinsonism that was responsive to levodopa.
      Phosphoglycerate kinase (PGK) activity was markedly decreased in muscle, and
      molecular analysis of the PGK1 gene identified the p.T378P mutation that was
      recently reported in a patient with isolated myopathy. This case reinforces the
      concept that PGK deficiency is a clinically heterogeneous disorder and raises the
      question of a relationship between PGK deficiency and idiopathic juvenile
      Parkinson disease.

PMID- 20151464
TI  - SB431542 treatment promotes the hypertrophy of skeletal muscle fibers but
      decreases specific force.
AB  - The small molecule inhibitor SB431542 inhibits activin type I receptors. The
      muscle growth-inhibitor myostatin binds to and signals via these receptors. The
      aim of this study was to test the hypothesis that SB431542 can inhibit myostatin
      related Smad signaling and induce muscle growth in cultured C2C12 myotubes and
      increase growth and specific force in cultured Xenopus muscle fibers. The effect
      of SB431542 was assessed in vitro on C2C12 myotubes and ex vivo using mature
      Xenopus muscle fibers. SB431542 treatment reduced myostatin-induced C-terminal
      Smad2 phosphorylation and resulted in the formation of enlarged myotubes. However
      myogenin expression was unchanged, while p70 S6k phosphorylation at Thr389, total
      myosin heavy chain, and the rate of protein synthesis were all reduced. Mature
      Xenopus muscle fibers that were treated with SB431542 had a higher fiber cross
      sectional area but decreased specific force production than control. SB431542 can
      initially antagonize myostatin signaling, but long-term unexpected signaling
      effects occur. Muscle fibers hypertrophy, but their specific force decreases
      compared to control.

PMID- 20151465
TI  - The inhibitory effect of a chewing task on a human jaw reflex.
AB  - This study was undertaken to investigate whether an inhibitory jaw reflex could
      be modulated by experimentally controlled conditions that mimicked symptoms of
      temporomandibular disorders. Reflecting on previous work, we anticipated that
      these conditions might suppress the reflex. Electromyographic recordings were
      made from a masseter muscle in 18 subjects, while electrical stimuli were applied
      to the upper lip. An inhibitory reflex wave (mean latency 47 ms) was identified
      and quantified. Immediately following an accelerated chewing task, which in most
      cases produced muscle fatigue and/or pain, the size of the reflex wave decreased
      significantly by about 30%. The suppression of inhibitory jaw reflexes by fatigue
      and pain may result in positive feedback, which may contribute to the symptoms of
      temporomandibular disorders. Future studies of temporomandibular disorder
      sufferers will help to determine whether such reflex changes reflect the
      underlying etiology and/or are a result of the temporomandibular disorder itself.

PMID- 20151466
TI  - Dorsal caudal tail and sciatic motor nerve conduction studies in adult mice:
      technical aspects and normative data.
AB  - Mice provide an important tool to investigate human neuromuscular disorders. The
      variability of electrophysiological techniques limits direct comparison between
      studies. The purpose of this study was to establish normative motor nerve
      conduction data in adult mice. The dorsal caudal tail nerve and sciatic nerve
      motor conduction studies were performed bilaterally on restrained anesthetized
      adult mice. The means and standard deviations for each electrophysiological
      parameter were determined in normal mice. Data were compared with inflammatory
      demyelinating polyneuropathy mice to determine whether these parameters
      discriminate between normal and abnormal peripheral nerves. Normal adult mice had
      a distal latency of 0.89 (+/-0.17) ms and 0.75 (+/-0.09) ms, distal compound
      motor unit action potential amplitude of 13.2 (+/-5.9) mV and 28.1 (+/-8.3) mV,
      and conduction velocity of 74.6 (+/-9.0) m/s and 76.5 (+/-8.3) m/s, respectively.
      These data were validated by the finding of statistically significant differences
      in several electrophysiological parameters that compared normal and
      polyneuropathy-affected mice. A standardized method for motor nerve conduction
      studies and associated normative data in mice should facilitate comparisons of
      disease severity and response to treatment between studies that use similar
      models. This would assist in the process of translational therapeutic drug design
      in neuromuscular disorders.

PMID- 20151467
TI  - Muscle weakness and atrophy are associated with decreased regenerative capacity
      and changes in mTOR signaling in skeletal muscles of venerable (18-24-month-old)
      dystrophic mdx mice.
AB  - The muscles of mdx mice progressively deteriorate with age. We wanted to know
      whether this is associated with a decrease in regenerative capacity and/or
      changes in the mammalian target of rapamycin complex (mTOR) signaling pathway.
      Muscles of mdx mice aged 5 weeks, 5, 12, and 18-24 months were studied. Maximal
      force and muscle weight of the older mice were decreased as compared to younger
      adult mice. Activation of the mTOR signaling pathway, i.e., phosphorylation of
      Akt (also known as protein kinase B) and ribosomal protein S6 was also reduced in
      the older mice. Moreover, 14 days after cardiotoxin injury the degree of recovery
      of maximal force and muscle weight were less in the older mice. In contrast to
      younger mice, there was also activation of the mTOR pathway during regeneration
      in the older mice. Progressive muscle weakness and atrophy in mdx mouse muscle is
      associated with a decline in regenerative potential and changes in activation of
      the mTOR signaling pathway.

PMID- 20151468
TI  - Preservation of muscle spindles in a 27-year-old Duchenne muscular dystrophy
      patient: importance for regenerative medicine strategies.

PMID- 20151469
TI  - Urodynamic standardization in a large-scale, multicenter clinical trial examining
      the effects of daily tadalafil in men with lower urinary tract symptoms with or
      without benign prostatic obstruction.
AB  - AIMS: To present the methodology, standardization techniques, and results from
      post hoc test-retest reproducibility analyses for a large, placebo-controlled,
      multicenter trial, employing urodynamic studies (UDS) to assess the impact of
      daily tadalafil on men with lower urinary tract symptoms (LUTS) with or without
      benign prostatic obstruction (BPO). METHODS: UDS implemented International
      Continence Society (ICS) Good Urodynamic Practice guidelines and standardized
      urodynamic and LUTS terminology. Further standardization procedures included:
      equipment calibration; a detailed procedure manual and centralized training; and
      implementation of a central reader. Measures included: monitoring of invalid
      studies, comparison of actual versus expected standard deviation (SD) for primary
      outcome (detrusor pressure at maximum urinary flow rate [p(detQmax)]), and test
      retest reproducibility of the placebo arm at baseline and endpoint. RESULTS: Two
      hundred men with moderate to severe LUTS (baseline IPSS >or=13) at 20 sites were
      randomized to receive either tadalafil 20 mg or placebo. All men underwent non
      invasive uroflow and pressure-flow studies. Numbers of invalid studies at
      baseline and endpoint were 9.3% and 0.6%, respectively. Variability of p(detQmax)
      was lower than anticipated based on actual versus expected SD of 15 and 30,
      respectively. Correlation coefficients were very good for pressure-flow
      parameters including p(detQmax) (r = .83). CONCLUSIONS: Multicenter clinical
      trials using urodynamic outcomes require additional standardized procedures to
      limit inter-site variability. By implementing centralized training with a
      detailed procedure manual and use of a central reader, we were able to limit
      common difficulties arising in multicenter clinical trials, as well as
      demonstrate good test-retest reproducibility of pressure flow measures.

PMID- 20151470
TI  - The beta3-adrenoceptor mediates the inhibitory effects of beta-adrenoceptor
      agonists via the urothelium in pig bladder dome.
AB  - AIMS: Relaxation of detrusor muscle via beta-adrenoceptors may contribute to
      urine storage during bladder filling. Thus there is increasing interest in beta
      adrenoceptor agonists as a potential treatment for detrusor overactivity. The
      role of the urothelium in bladder responses to beta-adrenoceptor agonists is not
      yet clear, although we have shown that these agonists have a greater inhibitory
      effect on detrusor contraction when the urothelium is intact. The aim was to
      determine which beta-adrenoceptor subtype is involved in this effect. METHODS:
      Paired strips of pig bladder dome mucosa-intact and mucosa-denuded, were mounted
      in tissue baths. Relaxation responses were obtained to beta-adrenoceptor agonists
      (isoprenaline, dobutamine, salbutamol or BRL37344) in carbachol pre-contracted
      tissues. Inhibitory effects were studied by obtaining concentration-response
      curves (CRCs) to carbachol in the presence and absence of beta-adrenoceptor
      agonists. The inhibitory effects of isoprenaline were also studied following
      incubation with beta-adrenoceptor antagonists (propranolol, CGP20712, ICI-118,
      551 or SR 59230A; non selected, beta(1), beta(2) and beta(3) selective
      respectively). RESULTS: isoprenaline, dobutamine, salbutamol and BRL37344 all
      relaxed carbachol pre-contracted tissues and responses were similar in intact and
      denuded strips. In inhibition experiments, beta-adrenoceptor agonists caused
      rightward shifts of carbachol CRCs. In intact strips the shift was greater with
      isoprenaline and BRL37344, but not with dobutamine or salbutamol. This increased
      shift was still observed in tissues pre-incubated with propranolo, CGP20712 and
      ICI-118, 551, but not with SR 59230A. CONCLUSIONS: beta(3)-adrenoceptors are
      involved in mediating inhibitory effects of beta-adrenoceptor agonists on
      detrusor contractions via the urothelium in pig bladder dome.

PMID- 20151471
TI  - Hemocytes of the cochineal insect: ultrastructure.
AB  - Using transmission electron microscopy, light microscopy (Giemsa May-Grumwald),
      and the Periodic Acid-Schif (PAS) and Sudan Black B staining techniques,
      hemocytes in the hemolymph of adult female Dactylopius coccus were characterized.
      The following, in order of abundance, were found: granulocytes, plasmatocytes,
      prohemocytes, and oenocytoids. Granulocytes varied in size with granulations in
      the cytoplasm, a large quantity of mitochondria, rugose endoplasmatic reticulum,
      ribosomes and vesicles, central or exocentric, spherical and occasionally
      lobulate nucleus. Plasmatocytes were polymorphic with irregularities in the
      plasma membrane; cytoplasm contained mitochondria, rugose endoplasmatic reticulum
      and vesicles, and exocentric, spherical, or irregular nucleus. In both types of
      hemocytes, scant polysaccharides and lipids were found. Prohemocytes were small
      and spherical with homogeneous cytoplasm and large exocentric nuclei. Oenocytoids
      were oval or irregular with dense homogeneous cytoplasm and elongated exocentric
      nuclei. The percentages of granulocytes on different days (d 1 and 10) during the
      life of the adult female were significantly different, as were those of
      plasmatocytes on d 30 and 50 and prohemocytes on d 1 and 50.

PMID- 20151473
TI  - Cadmium-induced increase in uterine wet weight and its mechanism.
AB  - BACKGROUND: Cadmium (Cd) increases in uterine wet weight in rodents remain
      unclear and there are only a few studies that examined the effects of Cd on
      uterine morphology. It is unknown whether Cd induces a uterotrophic effect via
      its interaction with the estrogen receptor (ER). In our study, we compared the
      effects of cadmium chloride (CaCl(2)) on uterine wet weight and morphology to
      those of 17beta-estradiol in Sprague-Dawley (SD) rats. METHODS: Forty-eight SD
      rats (23 days of age) were ectomized and randomly divided into six groups (eight
      rats per group): vehicle control (sterile saline solution), positive control
      (17beta-estradiol, 0.03 mg/kg in peanut oil), and CaCl(2) groups (0.0064, 0.032,
      0.16, and 0.8 mg/kg, respectively). The animals were treated by daily
      intraperitoneal (i.p.) injection for 3 days. The uteri were removed and assessed
      for weight, morphology, and immunohistochemical analysis. RESULTS: Compared to
      the control group, the uterine wet weight, the thickness of endomerium, the
      thickness of the stroma and the nucleus/cytoplasm ratio in the 17beta-estradiol
      treated and 0.8 mg/kg-day CaCl(2)-treated groups changed (P<0.01 or P 0.05). The
      endometrial gland number, the uterine epithelial cell height, and the PCNA
      positive expression in 17beta-estradiol-treated rats increased compared to that
      of the control (P<0.01), but not in the CaCl(2) dose groups. CONCLUSIONS: These
      results indicate that cadmium may induce an increase in uterine wet weight.
      However, this effect is not similar to that caused by 17beta-estradiol,
      suggesting it is not via Ca-ER interactions.

PMID- 20151472
TI  - BMP regulation of myogenesis in zebrafish.
AB  - In amniotes, BMP signaling from lateral plate and dorsal neural tube inhibits
      differentiation of muscle precursors in the dermomyotome. Here, we show that BMPs
      are expressed adjacent to the dermomyotome during and after segmentation in
      zebrafish. In addition, downstream BMP pathway members are expressed within the
      somite during dermomyotome development. We also show that zebrafish dermomyotome
      is responsive to BMP throughout its development. Ectopic overexpression of Bmp2b
      increases expression of the muscle precursor marker pax3, and changes the time
      course of myoD expression. At later stages, overexpression increases the number
      of Pax7+ myogenic precursors, and delays muscle differentiation, as indicated by
      decreased numbers of MEF2+ nuclei, decreased number of multi-nucleated muscle
      fibers, and an increased myotome angle. In addition, we show that while BMP
      overexpression is sufficient to delay myogenic differentiation, inhibition of BMP
      does not detectably affect this process, suggesting that other factors
      redundantly inhibit myogenic differentiation.

PMID- 20151475
TI  - I've been reading a lot about vitamin D lately.  What are the benefits, and how
      can I make sure I'm getting a sufficient amount?

PMID- 20151474
TI  - Developmental biomarkers of aging in Caenorhabditis elegans.
AB  - The developmental process of the nematode Caenorhabditis elegans is famously
      invariant; however, these animals have surprisingly variable lifespans, even in
      extremely homogenous environments. Inter-individual differences in muscle
      function decline, accumulation of lipofuscin in the gut, internal growth of food
      bacteria, and ability to mobilize heat-shock responses all appear to be
      predictive of a nematode's remaining lifespan; whether these are causal, or mere
      correlates of individual decline and death, has yet to be determined. Moreover,
      few "upstream" causes of inter-individual variability have been identified. It
      may be the case that variability in lifespan is entirely due to stochastic damage
      accumulation; alternately, perhaps such variability has a developmental origin
      and/or genes involved in developmental canalization also act to buffer phenotypic
      heterogeneity later in life. We review these two hypotheses with an eye toward
      whether they can be experimentally differentiated.

PMID- 20151476
TI  - I've just been diagnosed with multiple sclerosis, an autoimmune disease. What can
      you tell me about these diseases?

PMID- 20151477
TI  - Dental enamel.  Hard, but not invincible.

PMID- 20151478
TI  - High resting heart rate possible health risk for women.

PMID- 20151479
TI  - Endometrial cancer.  Caught early, often curable.

PMID- 20151480
TI  - I'm 68 and have rarely had headaches.  But recently I've had quite a few, often
      after exercise.  My doctor wants me to have a number of tests.  What could be
      causing this?

PMID- 20151481
TI  - My grandson wants to sing in a "screamo" band.  I told him he's going to hurt his
      voice, but he says he can prevent that by drinking a lot of water.  What do you
      think?

PMID- 20151482
TI  - Proceedings from the 17th European Safety and Reliability Conference, ESREL 2006,
      Estoril, Portugal, 18-22 September 2006.

PMID- 20151483
TI  - Proceedings from Semantic Web Applications and Tools for Life Sciences, 2008. 
      Edinburgh, UK. 28 November 2008.

PMID- 20151484
TI  - Proceedings from Sixth Annual MCBIOS Conference. Transformational Bioinformatics:
      Delivering Value from Genomes. Starkville, MS, USA. 20-21 February 2009.

PMID- 20151485
TI  - Inflammation and Carcinogenesis in the Pancreas and Biliary Tract: Mechanism and
      Practice - Proceedings from the Fifth Joint Meeting of the Japanese Society of
      Gastroenterology and the American Gastroenterological Association.

PMID- 20151486
TI  - Proceedings of the 40th Annual Meeting of the Austrian Society for Tropical
      Medicine and Parasitology. November 2-4, 2006, Linz.

PMID- 20151488
TI  - Special Issue: Proceedings of the Consensus Conference on Intracranial
      Atherosclerotic Disease.

PMID- 20151487
TI  - Clostridium difficile: Highlights from Anaerobe 2008, the 9th Biennial Congress
      of the Anaerobe Society of the Americas, Long Beach, California, USA, June 24-27,
      2008.

PMID- 20151489
TI  - Proceedings from the symposium "Neurobiology of Neuro-Psychiatric Diseases",
      Jerusalem, Israel, 2-5 November 2008.

PMID- 20151490
TI  - Proceedings and selected abstracts from 1st International Conference on Clinical
      Neonatology, Torino, Italy, November 2009.

PMID- 20151491
TI  - Global Advisory Committee on Vaccine Safety,3-4 December 2009.

PMID- 20151492
TI  - Yellow fever fact sheet.

PMID- 20151493
TI  - Update on oseltamivir-resistant pandemic A (H1N1) 2009 influenza virus: January
      2010.

PMID- 20151494
TI  - Human plague: review of regional morbidity and mortality, 2004-2009.

PMID- 20151495
TI  - Leprosy fact sheet (revised in February 2010).

PMID- 20151496
TI  - Update on human cases of highly pathogenic avian influenza A (H5N1) infection:
      2009.

PMID- 20151497
TI  - Meeting of the International Task Force for Disease Eradication, October 2009.

PMID- 20151498
TI  - Adolescent clinical care: integrating art & science . Abstracts of the Society
      for Adolescent Medicine Annual Meeting. Toronto, Ontario, Canada. April 7-10,
      2010.

PMID- 20151499
TI  - [French exchanges in thoracic oncology, IFCT Intergroupe Francophone de
      Cancerologie Thoracique].

PMID- 20151500
TI  - 2010 federal budget boosts funding for mental health and substance abuse
      programs.

PMID- 20151501
TI  - Charles Hilton Fagge (1838-1883): an early skin  physician in London.

PMID- 20151502
TI  - [Discussion about ethics necessary].

PMID- 20151503
TI  - [Sick-listed dragged into Kafka processes].

PMID- 20151504
TI  - [Antibiotic prophylaxis seldom indicated in dental care: important that
      physicians and dentists agree].

PMID- 20151505
TI  - [Soon more and more Swedish centenarians. Increased 10 times since 1970].

PMID- 20151507
TI  - [Ethics the basis of every physician's everyday].

PMID- 20151506
TI  - [Surfactant history. Great discovery for the smallest children].

PMID- 20151508
TI  - [From physician paternalism to patient autonomy].

PMID- 20151509
TI  - [Students need to train ethics during clinical practice].

PMID- 20151510
TI  - [Ethical competence development--is it possible?].

PMID- 20151511
TI  - [Health care methods should be analysed from an ethical perspective].

PMID- 20151512
TI  - [When ethical rules pull in different directions].

PMID- 20151513
TI  - [Physician as a risk-analyst].

PMID- 20151514
TI  - [Disinformation about the risks of adverse effect for children and fetuses of
      thiomersal in the vaccine].

PMID- 20151515
TI  - [The level of mercury in Pandemrix is not associated with increased health risk].

PMID- 20151516
TI  - [Risky to combine clopidogrel with proton pump inhibitor?].

PMID- 20151517
TI  - [Health care needs and accessibility: how to improve health of vulnerable
      groups?].

PMID- 20151518
TI  - [One shouldn't kill hope].

PMID- 20151519
TI  - [Guidelines on clinical rotation periods for medical residents in anesthesiology
      and postanesthesia recovery care].

PMID- 20151520
TI  - [Efficacy of obturator and femoral cutaneous nerve blocks for postoperative
      analgesia in hip surgery].
AB  - OBJECTIVES: The treatment of pain after surgery to repair a hip fracture is
      essential for an early start of rehabilitation and for reducing morbidity and
      mortality. Given that patients are elderly and have multiple medical conditions,
      local-regional analgesia can be an effective approach. Our aim was to compare the
      efficacy of obturator and femoral cutaneous nerve blocks and total intravenous
      analgesia in terms of level of patient satisfaction, complications, start of
      rehabilitation, and cost. PATIENTS AND METHODS: Prospective study of 75 patients
      undergoing surgery to repair hip fractures. Patients were randomized to receive
      intravenous analgesia only, blockade of both nerves, or blockade of only the
      obturator nerve. In each group we recorded visual analog scale (VAS) pain scores,
      satisfaction with postoperative analgesia, time elapsed until start of
      rehabilitation, need for postoperative analgesics, side effects, and the cost of
      drugs. RESULTS: Analgesia was significantly more effective in patients with nerve
      blocks than in those who received only intravenous analgesia (mean [SD] VAS
      scores, 2.6 [1.4] and 5.6 [0.7], respectively). Patients with nerve blocks also
      had a pain-free period of more than 24 hours (P < .001), needed fewer doses of
      supplementary analgesics or other drugs, had fewer side effects (P < .01),
      started rehabilitation earlier (32.6 [5.4] hours vs 45.7 [8.2] hours), generated
      less expenditure (2.6 Euros [1.5 Euros]/patient vs 7.0 Euros [0.4
      Euros]/patient). The tested techniques had no complications. CONCLUSIONS: The
      nerve blocks were effective, easy to perform, and safe. They afforded numerous
      advantages: extended period of postoperative analgesia, fast recovery, lower
      costs, and no complications.

PMID- 20151521
TI  - [Assessment of training in the control of acute postoperative pain based on
      analysis of pretraining and posttraining measures].
AB  - OBJECTIVE: To assess the efficacy of an acute pain unit's training on
      postoperative pain control for staff of trauma-orthopedic and general surgery
      departments. METHODS: Prospective pretest-posttest study in a tertiary care
      hospital. Physicians and nurses in the 2 surgical departments were given training
      sessions that included discussion with visual support and presentation of the
      acute pain unit's treatment protocols. Outcome measures used were visual analog
      scale (VAS) scores, patient satisfaction scores, number of days of treatment in
      accordance with the acute pain unit's protocol, and reasons for stopping
      treatment. Data for the year before and after the training program were analyzed.
      RESULTS: Data for 854 patients before training and 971 after training were
      analyzed. There were no differences between surgical specialties in the mean
      number of days of treatment. Nor did patient satisfaction scores differ (trauma
      orthopedic surgery, -0.379, P = .352; general surgery, -0.927, P = .177). VAS
      score differences of less than 0.5 points were found in active and resting pain
      from the second and third days, respectively. There was improvement in both
      specialties in terms of the number of patients who completed the treatment
      initially prescribed by the acute pain unit. CONCLUSIONS: The staff training in
      postoperative pain control did not affect patient satisfaction, though a small
      improvement in active and resting VAS scores was noted. The training did have an
      effect on significantly improving overall compliance with the acute pain unit's
      treatment protocols.

PMID- 20151522
TI  - [Influence of gender on the potency and course of action of rocuronium bromide].
AB  - OBJECTIVE: The correlation between gender and the potency of certain
      neuromuscular blockers, including rocuronium, has been investigated. However, the
      methods used have been inconsistent. This study aimed to look further at the role
      of gender in order to arrive at definitive conclusions. PATIENTS AND METHODS: In
      a first and second phases of the study, rocuronium dose-response curves were
      constructed for patient groups as follows: 2 mixed-gender groups, 2 female
      groups, and 2 male groups. One group in each set received a single dose. In the
      other group the effect of the accumulated dose was measured after each of 3
      fractions. The doses were transformed logarithmically. The effect was monitored
      by electromyography, and probit analysis was used to calculate the effective dose
      to induce 50%, 90% and 95% of the maximum effect (ED50, ED90 and ED95,
      respectively) in each patient. In the third phase, a bolus dose of 400 microg-Kg(
      1) was administered to 3 additional groups. Onset time, maximum effect, speed of
      onset, duration of effect as the 10%-25% recovery index, and speed of recovery
      were recorded. In the fourth phase analysis was restricted to measurements during
      the period of onset. RESULTS: No significant between-group differences in mean
      (SD) ED50, ED90, or ED95 values were observed after single doses (female group:
      176 [68], 252 [97], and 285 [110] microg x Kg(-1), respectively; male group: 187
      [69], 271 [100], and 307 [114] microg x Kg(-1); mixed group: 172 [73], 233 [98],
      and 258 [109] microg x Kg(-1)). Assessment of effect after cumulative fracional
      doses gave the following mean values for ED50, ED90, and ED95: 249 (63), 310
      (79), and 334 (85) microg x Kg(-1) for the female group; 261 (60), 327 (75), and
      354 (81) microg x Kg(-1) for the male group; and 242 (70), 305 (88), and 330 (95)
      microg x Kg(-1) for the mixed group. No significant differences in measures of
      effect were found after bolus administration in the third phase. CONCLUSIONS:
      These results suggest that there is no significant effect of gender on potency or
      course of action of rocuronium bromide. Reports of such differences based on
      previous studies may be the result of problems in the methods applied.

PMID- 20151523
TI  - Peripartum implications of caffeine intake in pregnancy: is there cause for
      concern?
AB  - Maternal use of "social drugs" such as caffeine, ethanol and tobacco in pregnancy
      is on increase- -worldwide. Caffeine is probably the most frequently ingested
      pharmacologically active substance in the world. It is found in common beverages
      (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in
      medications. Because of its wide consumption at different levels by most segments
      of the population, the public and the scientific community have expressed
      interest in the potential for caffeine to produce adverse effects on human
      health. Reproductive-aged and pregnant women are 'at risk' subgroups of the
      population who may require specific advice on moderating their daily caffeine
      intake. This article highlights the implications of caffeine intake in pregnancy,
      reviews the latest evidence-based information available on this subject, and
      offers recommendations (practical advice) for anesthesiologists and obstetrician
      gynecologists proving peripartum care to these potentially complicated
      pregnancies.

PMID- 20151525
TI  - [Merging the specialty of anesthesiology and postanesthesia recovery care
      medicine with intensive care medicine].

PMID- 20151524
TI  - [Use of neuromuscular blocking agents and reversal of blockade: guidelines from
      Sociedad Espanola de Anestesiologia, Reanimacion y Terapeutica del Dolor].

PMID- 20151526
TI  - [Treating severe acute anemia due to vaginal bleeding in the Jehovah's Witness: a
      report of 2 cases].
AB  - For reasons of religious belief, Jehova's Witnesses do not accept blood
      transfusions or the infusion of blood products. In situations in which severe,
      life-threatening anemia develops, patient refusal to receive a transfusion can
      create serious ethical and legal problems. The principle of patient autonomy,
      which implies the freedom to accept or reject treatment, comes into conflict with
      the physician's obligation to safeguard the patient's life using all means
      possible. We report 2 cases of severe anemia in Jehova's Witnesses. One was due
      to menorrhagia and the other to postpartum bleeding. The physician should be
      aware of alternatives to infusion of blood products and know how to cope with an
      unexpected critical event in these patients. The measures we took were effective
      in our patients. In the case of menorrhagia, hormone treatment is effective when
      the woman wishes to preserve the ability to conceive and avoid surgery
      (endometrial ablation and hysterectomy). In postpartum bleeding refractory to
      conservative treatment, selective embolization of bleeding vessels may make it
      unnecessary to resort to more aggressive treatment, such as obstetric
      hysterectomy.

PMID- 20151527
TI  - [Lung transplant in patients with sarcoidosis: 2 case reports and a
      pathophysiologic review].
AB  - Lung transplantation is an appropriate therapeutic option for patients with
      advanced sarcoidosis that has not responded to medical treatment. The causes of
      sarcoidosis are unknown and the course of disease and prognosis are highly
      variable. As it is difficult to determine the ideal timing for a transplant or
      the type of transplant to perform, this may influence the high perioperative
      mortality in these patients. Postoperative morbidity and mortality rates are high
      when pulmonary hypertension is present before the transplant or when primary
      graft failure, acute rejection, infection, or other complications develop
      afterwards. We describe 2 patients with a diagnosis of end-stage sarcoidosis who
      received a lung transplant and a heart-lung transplant. The outcomes were
      different in each case. We analyze factors related to morbidity and mortality
      that determined the outcomes.

PMID- 20151528
TI  - [Loss of consciousness and respiratory depression after a retrobulbar
      intraorbital block for eye surgery: a case report].

PMID- 20151529
TI  - [Phenic nerve paralysis after radical cervical lymph node removal in a patient
      with chronic obstructive pulmonary disease and sleep apnea-hypopnea syndrome].

PMID- 20151530
TI  - [Tracheotomy guided by fiberoptic bronchoscopy through an i-gel supraglottic
      airway device].

PMID- 20151531
TI  - [Reactive thrombocytosis: on the importance of hemostasis monitoring].

PMID- 20151532
TI  - [Ketamine combined with remifentanil for pediatric ear surgery].

PMID- 20151533
TI  - [Continuous monitored insufflation to compensate for a tracheal cuff air leak].

PMID- 20151534
TI  - [Pulmonary edema following lung re-expansion after fiberoptic inspection of a
      massive paraneoplastic pleural effusion].

PMID- 20151535
TI  - Molecular collisions, from warm to ultracold.
AB  - This introductory article contrasts molecular collisions, particularly reactive
      collisions, in the familiar "warm" domain with the ultracold regime where the
      relative deBroglie wavelengths become long compared with the range of interaction
      of the collision partners. Ultracold collisions have much greater sensitivity to
      entrance channel interactions, so offer the prospect of tuning by external fields
      to control onset of reaction. However, for ultracold collisions, kinematic
      constraints impose severe limitations on the observable dynamical properties. In
      the exit channel for appreciably exoergic reactions, the deBroglie wavelengths
      become short, so the exit dynamics are much like those for warm collisions.
      Reactions of alkali dimers, halides, and monoxide molecules are discussed that
      seem especially congenial for cold collision studies.

PMID- 20151536
TI  - Testing the time-invariance of fundamental constants using microwave spectroscopy
      on cold diatomic radicals.
AB  - The recently demonstrated methods to cool and manipulate neutral molecules offer
      new possibilities for precision tests of fundamental physics theories. We here
      discuss the possibility of testing the time-invariance of fundamental constants
      using near degeneracies between rotational levels in the fine structure ladders
      of molecular radicals. We show that such a degeneracy occurs between the J = 6,
      Q2 1 and the J = 8, Q = 0 levels of the various natural isotopomers of carbon
      monoxide in its a 3pi state. As a result, the 2-photon transition that connects
      these states is 300 times more sensitive to a variation of m(p)/m(e) than a pure
      rotational transition. We present a molecular beam apparatus that might be used
      to measure these transitions with a fractional accuracy of 10(-12). Ultimately,
      the precision of an experiment on metastable CO will be limited by the lifetime
      of the a 3pi state. We will discuss other possible molecules that have a suitable
      level structure and can be cooled using one of the existing methods.

PMID- 20151537
TI  - Prospects for measuring the electric dipole moment of the electron using
      electrically trapped polar molecules.
AB  - Heavy polar molecules can be used to measure the electric dipole moment of the
      electron, which is a sensitive probe of physics beyond the Standard Model. The
      value is determined by measuring the precession of the molecule's spin in a plane
      perpendicular to an applied electric field. The longer this precession evolves
      coherently, the higher the precision of the measurement. For molecules in a trap,
      this coherence time could be very long indeed. We evaluate the sensitivity of an
      experiment where neutral molecules are trapped electrically, and compare this to
      an equivalent measurement in a molecular beam. We consider the use of a Stark
      decelerator to load the trap from a supersonic source, and calculate the
      deceleration efficiency for YbF molecules in both strong-field seeking and weak
      field seeking states. With a 1 s holding time in the trap, the statistical
      sensitivity could be ten times higher than it is in the beam experiment, and this
      could improve by a further factor of five if the trap can be loaded from a source
      of larger emittance. We study some effects due to field inhomogeneity in the trap
      and find that rotation of the electric field direction, leading to an
      inhomogeneous geometric phase shift, is the primary obstacle to a sensitive trap
      based measurement.

PMID- 20151538
TI  - Buffer gas cooling of polyatomic ions in rf multi-electrode traps.
AB  - Cooling all degrees of freedom of a molecule, a cluster, or even a nanoparticle
      which is suspended in a vacuum, is an experimental challenge. Without suitable
      schemes, cold or ultracold chemical reactions are not feasible. Methods such as
      laser based preparation of very slow atoms, decelerating molecules to low
      velocities with electric fields or freezing molecular ions into Coulomb crystals,
      are generally not suitable to cool the vibrational or rotational motion of
      molecules. This contribution describes a new method in which a beam of slow atoms
      or molecules (H, He, H2, or D2) is used for cooling charged particles confined in
      a multi-electrode rf trap. For reaching sub-K temperatures, the fast part of a
      cold effusive beam is removed with a shutter before the slow remaining neutrals
      interact with the ion cloud. The development of a pulsed cold beam source is
      discussed as well as suitable methods for determining the ion temperature. A
      challenging application is to prepare internally cold CH5+ for spectroscopy or
      chemistry. New experimental results for hydrogen abstraction in collisions with
      slow H atoms are reported at energies of a few meV. For evaluating these
      measurements and for predicting effective rate coefficients at lower energies,
      the kinematic conditions of the slow neutral beam-ion trap arrangement have been
      analyzed in detail. The potential of cooling ions such as protonated methane or
      H3+ with slow energy selected H atoms is briefly mentioned. An interesting
      process is the formation of weakly bound ions such as H4+ or CH6+ via radiative
      or ternary association. Such ions are ideal candidates for preparing the
      corresponding collision complexes very close (microeV) to the dissociation
      continuum using infrared transitions.

PMID- 20151539
TI  - Ion-molecule chemistry at very low temperatures: cold chemical reactions between
      Coulomb-crystallized ions and velocity-selected neutral molecules.
AB  - The recent development of a range of techniques for producing cold atoms and
      molecules at very low translational temperatures T < or = 1 K has provided the
      opportunity to investigate collisional processes in a new physical regime. We
      have recently presented a new experimental method to study low-temperature
      reactive collisions between translationally cold ions and neutral molecules (S.
      Willitsch et al., Phys. Rev. Lett. 2008, 100, 043203). Our technique relies on
      the combination of a quadrupole-guide velocity selector for the generation of
      translationally cold neutral molecules with a facility to produce ordered
      structures of cold ions (Coulomb crystals) by laser cooling in a linear
      quadrupole ion trap. The strong localisation of the ions in the trap in
      combination with the high sensitivity of laser-induced-fluorescence detection
      enabled us to study chemical reactions on the single-particle level, down to
      temperatures of T approximately 1 K. In the current paper, we present a detailed
      characterisation of the scope and limitations of this method based on our study
      of the reaction between laser-cooled Ca+ ions and velocity-selected CH3F
      molecules. The properties of our cold-neutrals source and the dependence of the
      measured rate constant on the shape of the Coulomb crystals, trapping and laser
      cooling parameters are discussed. An extension of our technique for the study of
      low-temperature reactions with sympathetically cooled molecular ions
      (translational temperature T > 10 mK) is presented and first results on the
      charge-transfer reaction between OCS+ and ND3 are discussed. Finally,
      perspectives for further developments of our method are explored.

PMID- 20151540
TI  - Collision experiments with Stark-decelerated beams.
AB  - The crossed molecular beam technique has been established as a mature and
      important experimental method for detailed studies of molecular interactions, and
      has contributed enormously to our present understanding of molecular reaction
      dynamics. The Stark deceleration technique yields unprecedented control over both
      the internal and external degrees of freedom of polar molecules in a molecular
      beam, offering new possibilities in scattering experiments. In particular, Stark
      decelerated molecular beams allow detailed molecular scattering studies as a
      function of the collision energy, from low to high collision energies, and with a
      very high energy resolution. We discuss a variety of experimental geometries that
      exploit this new molecular beam technology for scattering experiments, ranging
      from crossed beam arrangements and molecular synchrotrons to surface scattering
      set-ups.

PMID- 20151541
TI  - Dynamics of OH(2pi)-He collisions in combined electric and magnetic fields.
AB  - We use accurate quantum mechanical calculations to analyze the effects of
      parallel electric and magnetic fields on collision dynamics of OH(2pi) molecules.
      It is demonstrated that spin relaxation in 3He-OH collisions at temperatures
      below 0.01 K can be effectively suppressed by moderate electric fields of order
      10 kV cm(-1). We show that electric fields can be used to manipulate Feshbach
      resonances in collisions of cold molecules. Our theoretical results can be tested
      in experiments with OH molecules in Stark decelerated molecular beams and
      electromagnetic traps. PACS numbers: 33.20.-t, 33.80.Ps.

PMID- 20151542
TI  - Production of cold ND3 by kinematic cooling.
AB  - We have produced translationally cold ammonia (ND3) molecules in various quantum
      states by kinematic cooling. In these experiments, ND3 molecules are brought
      nearly to rest in the (J, K) = (2,0), (2,1), (2,2), (3,1), (3,2), and (3,3)
      rotational levels of the ground vibronic state by rotationally-inelastic
      collisions with Ne atoms. The cold molecules are produced in quantum-state
      dependent velocity distributions whose laboratory frame velocities are measured
      to be between 21 m s(-1) (E(trans)/k = 530 mk) and 32 m s(-1) (E(trans)/k = 1.2
      K), and are calculated to be between 7.5 m s(-1) (E(trans)/k = 70 mK) and 27 m s(
      1) (E(trans)/k = 880 mK). Due to systematic experimental effects, the measured
      velocities are upper limits to the actual velocities. These temperatures are low
      enough that it should be possible to use electrostatic traps to confine cold
      molecules in many of these quantum states.

PMID- 20151543
TI  - Manipulating the motion of large neutral molecules.
AB  - Large molecules have complex potential-energy surfaces with many local minima.
      They exhibit multiple stereo-isomers, even at very low temperatures. In this
      paper we discuss the different approaches for the manipulation of the motion of
      large and complex molecules, like amino acids or peptides, and the prospects of
      state- and conformer-selected, focused, and slow beams of such molecules for
      studying their molecular properties and for fundamental physics studies.

PMID- 20151544
TI  - Sympathetic cooling by collisions with ultracold rare gas atoms, and recent
      progress in optical Stark deceleration.
AB  - We propose a general scheme for sympathetic cooling of molecules to microK
      temperatures on a timescale of seconds. Experimental parameters have been
      estimated from theory, which indicate the viability of the scheme. This method,
      which is particularly suited to optical Stark deceleration, utilises ultracold,
      laser cooled metastable rare gas atoms quenched to their ground state as
      collision partners to co-trapped molecular species within a deep optical trap
      (150 mK). We also describe the measurement of the role of laser-induced molecular
      alignment on the dipole force in optical Stark deceleration and outline progress
      towards the realisation of chirped optical Stark deceleration for producing slow
      molecular beams with mK energy spreads.

PMID- 20151545
TI  - Prospects for sympathetic cooling of polar molecules: NH with alkali-metal and
      alkaline-earth atoms--a new hope.
AB  - We explore the potential energy surfaces for NH molecules interacting with alkali
      metal and alkaline-earth atoms using highly correlated ab initio electronic
      structure calculations. The surfaces for interaction with alkali-metal atoms have
      deep wells dominated by covalent forces. The resulting strong anisotropies will
      produce strongly inelastic collisions. The surfaces for interaction with alkaline
      earth atoms have shallower wells that are dominated by induction and dispersion
      forces. For Be and Mg the anisotropy is small compared to the rotational constant
      of NH, so that collisions will be relatively weakly inelastic. Be and Mg are thus
      promising coolants for sympathetic cooling of NH to the ultracold regime.

PMID- 20151546
TI  - Continuous guided beams of slow and internally cold polar molecules.
AB  - We describe the combination of buffer-gas cooling with electrostatic velocity
      filtering to produce a high-flux continuous guided beam of internally cold and
      slow polar molecules. In a previous paper (L.D. van Buuren et al., Phys. Rev.
      Lett., 2009, 102, 033001) we presented results on density and state purity for
      guided beams of ammonia and formaldehyde using an optimized set-up. Here we
      describe in more detail the technical aspects of the cryogenic source, its
      operation, and the optimization experiments that we performed to obtain the best
      performance. The versatility of the source is demonstrated by the production of
      guided beams of different molecular species.

PMID- 20151547
TI  - Broadband lasers to detect and cool the vibration of cold molecules.
AB  - By using broadband lasers, we demonstrate the possibilities for control of cold
      molecules formed via photoassociation. Firstly, we present a detection REMPI
      scheme (M. Viteau et al., Phys. Rev. A, 2009, 79, 021402) to systematically
      investigate the mechanisms of formation of ultracold Cs2 molecules in deeply
      bound levels of their electronic ground state X1sigma(g)+. This broadband
      detection scheme could be generalized to other molecular species. Then we report
      a vibrational cooling technique (M. Viteau et al., Science, 2008, 321, 232)
      through optical pumping obtained by using a shaped mode locked femtosecond laser.
      The broadband femtosecond laser excites the molecules electronically, leading to
      a redistribution of the vibrational population in the ground state via a few
      absorption-spontaneous emission cycles. By removing the laser frequencies
      corresponding to the excitation of the v = 0 level, we realize a dark state for
      the so-shaped femtosecond laser, leading, with the successive laser pulses, to an
      accumulation of the molecules in the v = 0 level, ie. a laser cooling of the
      vibration. The simulation of the vibrational laser cooling allows us to
      characterize the criteria to extend the mechanism to other molecular species (R.
      V. Krems, Int. Rev. Phys. Chem., 2005, 24, 99). We finally discuss the
      generalization of the technique to laser cooling of the rotation of the molecule.

PMID- 20151548
TI  - Dark state experiments with ultracold, deeply-bound triplet molecules.
AB  - We examine dark quantum superposition states of weakly bound Rb2 Feshbach
      molecules and tightly bound triplet Rb2 molecules in the rovibrational ground
      state, created by subjecting a pure sample of Feshbach molecules in an optical
      lattice to a bichromatic Raman laser field. We analyze, both experimentally and
      theoretically, the creation and dynamics of these dark states. Coherent
      wavepacket oscillations of deeply bound molecules in lattice sites, as previously
      observed by Lang et al. (Phys. Rev. Lett., 2008, 101, 133005), are suppressed due
      to laser-induced phase locking of molecular levels. This can be understood as the
      appearance of a novel multilevel dark state. In addition, the experimental
      methods developed help to determine important properties of our coupled atom/
      laser system.

PMID- 20151549
TI  - Precision molecular spectroscopy for ground state transfer of molecular quantum
      gases.
AB  - One possibility for the creation of ultracold, high phase space density quantum
      gases of molecules in the rovibronic ground state relies on first associating
      weakly-bound molecules from quantum-degenerate atomic gases on a Feshbach
      resonance and then transferring the molecules via several steps of coherent two
      photon stimulated Raman adiabatic passage (STIRAP) into the rovibronic ground
      state. Here, in ultracold samples of Cs2 Feshbach molecules produced out of
      ultracold samples of Cs atoms, we observe several optical transitions to deeply
      bound rovibrational levels of the excited 0(u)+ molecular potentials with high
      resolution. At least one of these transitions, although rather weak, allows
      efficient STIRAP transfer into the deeply-bound vibrational level (see text for
      symbols)v = 73 > of the singlet X1 sigma(g)+ ground state potential, as recently
      demonstrated (J. G. Danzl, E. Haller, M. Gustavsson, M. J. Mark, R. Hart, N.
      Bouloufa, O. Dulieu, H. Ritsch, and H.-C. Nagerl, Science, 2008, 321, 1062). From
      this level, the rovibrational ground state (see text for symbols)v = 0, J = 0 >
      can be reached with one more transfer step. In total, our results show that
      coherent ground state transfer for Cs2 is possible using a maximum of two
      successive two-photon STIRAP processes or one single four-photon STIRAP process.

PMID- 20151550
TI  - Rotational spectroscopy of single carbonyl sulfide molecules embedded in
      superfluid helium nanodroplets.
AB  - The pure rotation spectrum of carbonyl sulfide embedded in superfluid helium
      nanodroplets was measured in the frequency range from 4 to 15.5 GHz. Four lines,
      corresponding to the J = 1-0, J = 2-1, J = 3-2, and J = 4-3 transitions, were
      found. The line widths of the transitions increase with increasing rotational
      quantum number J, which is indicative of a distribution of the effective B
      rotational constant. A comparison of the pure rotational spectrum with the
      microwave-infrared double resonance spectrum [S. Grebenev, M. Havenith, F.
      Madeja, J. P. Toennies, and A. F. Vilesov, J. Chem. Phys., 2000, 113(20), 9060]
      reveals that the double resonance measurement scheme probes predominantly
      rotational transitions within the vibrationally excited state.

PMID- 20151551
TI  - Self-organisation and cooling of a large ensemble of particles in optical
      cavities.
AB  - We present an investigation of the dynamics of centre-of-mass of a neutral
      particle cloud in a cavity pumped by an optical field. We derive an expression
      for the pump threshold for spatial self-organization of the particles and analyze
      its scaling laws in terms of the system parameters. Using a newly developed
      statistical model, we simulate the dynamics of the particles and numerically
      obtain the scaling laws. We show good agreement between the analytic formulae and
      simulations. We further use the scaling relation to discuss the operating
      conditions for cavity cooling a large ensemble of particles. Finally, we study
      cavity cooling of an ensemble of molecules with an initial temperature of around
      10 mK. We show that 35% of the molecules are trapped by the optical field
      intensity in the cavity and a final temperature below 1 mK is reached.

PMID- 20151552
TI  - Formation of ultracold dipolar molecules in the lowest vibrational levels by
      photoassociation.
AB  - We recently reported the formation of ultracold LiCs molecules in the
      rovibrational ground state X1sigma+, v" = 0,J" = 0 (J. Deiglmayr et al., Phys.
      Rev. Lett., 2008, 101, 133004). Here we discuss details of the experimental setup
      and present a thorough analysis of the photoassociation step including the
      photoassociation line shape. We predict the distribution of produced ground state
      molecules using accurate potential energy curves combined with an ab initio
      dipole transition moment and compare this prediction with experimental ionization
      spectra. Additionally we improve the value of the dissociation energy for the
      X1sigma+ state by high resolution spectroscopy of the vibrational ground state.

PMID- 20151553
TI  - Ultracold polar molecules near quantum degeneracy.
AB  - We report the creation and characterization of a near quantum-degenerate gas of
      polar 40K-87Rb molecules in their absolute rovibrational ground state. Starting
      from weakly bound heteronuclear KRb Feshbach molecules, we implement precise
      control of the molecular electronic, vibrational, and rotational degrees of
      freedom with phase-coherent laser fields. In particular, we coherently transfer
      these weakly bound molecules across a 125 THz frequency gap in a single step into
      the absolute rovibrational ground state of the electronic ground potential. Phase
      coherence between lasers involved in the transfer process is ensured by
      referencing the lasers to two single components of a phase-stabilized optical
      frequency comb. Using these methods, we prepare a dense gas of 4 x 10(4) polar
      molecules at a temperature below 400 nK. This fermionic molecular ensemble is
      close to quantum degeneracy and can be characterized by a degeneracy parameter of
      T/T(F) = 3. We have measured the molecular polarizability in an optical dipole
      trap where the trap lifetime gives clues to interesting decay mechanisms. Given
      the large measured dipole moment of the KRb molecules of 0.5 Debye, the study of
      quantum degenerate molecular gases interacting via strong dipolar interactions is
      now within experimental reach. PACS numbers: 37.10.Mn, 37.10.Pq.

PMID- 20151554
TI  - Ultracold molecules from ultracold atoms: a case study with the KRb molecule.
AB  - Ultracold collisions of cold atoms or molecules make the bound states of the
      collision complex formed from the two colliding species accessible for control
      and manipulation of the cold species or the complex. Such resonances are best
      treated by a resonant scattering theory, which in the ultracold domain can take
      advantage of the properties of the long-range potential and the methods of
      multichannel quantum defect theory. Coupled channels calculations on the
      threshold scattering states and bound states of the 40K87Rb molecule illustrate
      the ideas and methodology of quantum defect theory using the long-range potential
      and also demonstrate the spin properties of the bound states throughout the
      spectrum.

PMID- 20151555
TI  - Two-photon coherent control of femtosecond photoassociation.
AB  - Photoassociation with short laser pulses has been proposed as a technique to
      create ultracold ground state molecules. A broad-band excitation seems the
      natural choice to drive the series of excitation and deexcitation steps required
      to form a molecule in its vibronic ground state from two scattering atoms. First
      attempts at femtosecond photoassociation were, however, hampered by the
      requirement to eliminate the atomic excitation leading to trap depletion. On the
      other hand, molecular levels very close to the atomic transition are to be
      excited. The broad bandwidth of a femtosecond laser then appears to be rather an
      obstacle. To overcome the ostensible conflict of driving a narrow transition by a
      broad-band laser, we suggest a two-photon photoassociation scheme. In the weak
      field regime, a spectral phase pattern can be employed to eliminate the atomic
      line. When the excitation is carried out by more than one photon, different
      pathways in the field can be interfered constructively or destructively. In the
      strong-field regime, a temporal phase can be applied to control dynamic Stark
      shifts. The atomic transition is suppressed by choosing a phase which keeps the
      levels out of resonance. We derive analytical solutions for atomic two-photon
      dark states in both the weak-field and strong-field regime. Two-photon excitation
      may thus pave the way toward coherent control of photoassociation. Ultimately,
      the success of such a scheme will depend on the details of the excited electronic
      states and transition dipole moments. We explore the possibility of two-photon
      femtosecond photoassociation for alkali and alkaline-earth metal dimers and
      present a detailed study for the example of calcium.

PMID- 20151556
TI  - A pump-probe study of the photoassociation of cold rubidium molecules.
AB  - The dynamics of the excited state during the photoassociation of cold molecules
      from cold rubidium atoms is studied in a series of pump-probe experiments. Dipole
      transitions similar to those of the atoms are observed in the molecular signal.
      While such behaviour is characteristic of the long-range molecules, the
      photoassociation of bound molecules is confirmed in additional experiments. The
      pump-probe signal observed on a 250 ps time scale did not, however, reveal
      wavepacket oscillations predicted by theory. This result is discussed using
      numerical simulations of photoassociation and a modification to the current
      experiments that could lead to the detection of wavepacket dynamics is suggested.

PMID- 20151557
TI  - Fano profiles in two-photon photoassociation spectra.
AB  - In this article we derive the lineshapes observed in two-photon photoassociation
      spectrocopy of molecules using an effective Hamiltonian adapted from previous
      work in atomic physics. The lineshape is decomposed in terms of sums and products
      of Breit-Wigner and Fano profiles, which we associate with physical absorption
      and emission processes, and to quantum interferences between transition
      amplitudes. We emphasize the specific features which do not exist in the atomic
      case, linked to the dissociation width of the photoassociated molecules in the
      electronic ground state.

PMID- 20151558
TI  - Concluding remarks: achievements and challenges in cold and ultracold molecules.

PMID- 20151559
TI  - Access to care.

PMID- 20151560
TI  - The value of a smile.

PMID- 20151561
TI  - Treatment considerations for bleaching and bonding white lesions in the anterior
      dentition.
AB  - White lesions occur commonly on the anterior teeth. There are numerous reasons
      why these lesions appear in the anterior dentition, and these reasons will be
      discussed in detail. For some patients, these white lesions may be considered
      unsightly and the patients may seek treatment to have them removed; other
      patients are not concerned about their presence on their anterior teeth. Some of
      the white lesions are caused by demineralization and occur because of poor oral
      hygiene. For the purpose of this article, developmental white lesions will be
      discussed in detail, along with the options for treatment of these lesions.

PMID- 20151562
TI  - The art of veneer cementation.
AB  - Creating a smile makeover is a complex process. It is a challenge that requires
      attention to detail in all areas. The most critical step in the process is the
      seating of the porcelain laminate veneers (PLVs). Both appearance and durability
      can be affected if mistakes are made in this phase of treatment.

PMID- 20151563
TI  - Aesthetic crown lengthening: a step by step surgical guide and biologic
      considerations.
AB  - For years now, dentistry has been in the aesthetics business. We have been
      talking about and offering dental restorations that look as close as possible to
      natural teeth-or perhaps look even better. We have been bleaching, veneering, and
      crowning in an effort to meet patient demand and expectations of that elusive
      "perfect smile." As these restorative treatments evolved, we became better at
      creating more translucent porcelains and composites, brighter shades, better
      color matching tools with the advent of electronic color matching, and more
      talented dental technicians-we are literally creating works of art. Yet some of
      this "art work" still falls short of the mark (Figure 1). Why is this? In many
      cases it is because we have forgotten to choose a frame that is deserving of our
      artwork.

PMID- 20151564
TI  - Aesthetic and biomechanical precision in complex cases.
AB  - The success of dental restorations should not only be measured by immediate
      outcomes, such as patient comfort and appearance, but also by long-term survival
      and stability of the definitive restorations. Long-term success is dependant on
      the level of precision at which treatment is carried out. The three main areas in
      which this precision should be focused are precision of fit, occiusal precision,
      and aesthetic precision.

PMID- 20151565
TI  - Invisalign and porecelain: the contemporary restorative powerhouse.
AB  - For years, restorative practices and traditional orthodontics stood largely
      separate from one another save for the most extreme instances. Orthodontics has
      evolved over the years, and a new breed of orthodontic technology appeared in the
      late 1990s. A clear alternative to traditional orthodontics emerged, and
      Invisalign (Align Technology, Inc., Santa Clara, CA) was born. Historically,
      orthodontics and restorative work, within a practice, rarely coincided on the
      same patient, but the advances within both disciplines have afforded a new and
      innovative way of considering conservative dentistry. No longer does there have
      to be aggressive preparation to attain a desired result. With patient
      understanding, a negligible amount of patience, and the desire to achieve the
      very best dentistry has to offer, the potential is limitless.

PMID- 20151566
TI  - [Of rabbits feet and cowards].

PMID- 20151567
TI  - [Compliance with handwashing and use of gloves: what is the effect of an
      intensive training program?].

PMID- 20151568
TI  - [Does one really forge one's own fortune?].

PMID- 20151569
TI  - ["Development promoting, family centered, individual care of newborn infants"].

PMID- 20151570
TI  - [BeKD informs: children have a right to nurse counseling].

PMID- 20151571
TI  - [Meningococcal infections].

PMID- 20151573
TI  - [Pediatric nurses and family midwives strengthen families. "Welcome baby" as
      preventive approach to family support].

PMID- 20151574
TI  - [Career related continuing education for active executives in nursing. DRk
      nursing societies and HAWK start nationwide unique cooperation in nursing
      education].

PMID- 20151575
TI  - [A nursing specialty career for pediatric nurses. Pediatric nursing student Jana
      Schucht completes 3 months of clinic external training at the Lowenherz Pediatric
      Hospice].

PMID- 20151576
TI  - [Licorice--only a snack or also a medicine?].

PMID- 20151577
TI  - [Baby sleep coaching].

PMID- 20151578
TI  - [Report from the Pediatric Intensive Care Specialty Congress 24 - 25 September
      2009].

PMID- 20151579
TI  - [3rd Expert Day of BKKO "Children have rights" 20 November 2009].

PMID- 20151580
TI  - ["Outstanding. for children" is outstanding for children].

PMID- 20151581
TI  - [Comment on the article, "Significance of disinfection the household is more
      important than ever" in issue 11/09, page 457].

PMID- 20151582
TI  - [Learning in coma vigilans is possible. Stimulus conditioning can replace brain
      studies].

PMID- 20151583
TI  - [Why does my urine look so different? What color can reveal].

PMID- 20151584
TI  - Pay-for-performance: quality programs at the crossroads.

PMID- 20151585
TI  - The opportunity of change.

PMID- 20151586
TI  - Interview with a quality leader: Michael Bailit on pay-for-performance. Interview
      by Deborah A Dowling.
AB  - Michael is the president of Bailit Health Purchasing, LLC, and has worked with a
      wide array of employer purchasers, government agencies, and purchasing coalitions
      across the United States since founding the firm in 1997. Michael's efforts have
      included extensive activity in the areas of Pay-for-Performance, reimbursement
      system design, quality improvement, and a medical home initiative design and
      implementation. Michael earned a Bachelor of Arts degree from Wesleyan University
      and earned an MBA from the Kellogg School of Management at Northwestern
      University.

PMID- 20151587
TI  - Impact of a pay-for-performance program on low performing physicians.
AB  - Studies have shown that the lowest performing physicians in pay-for-performance
      (P4P) programs improved the most; however, it is unclear whether this would occur
      without the P4P program or be sustained. The objective of this study is to
      investigate the impact of P4P in a Preferred Provider Organization (PPO) on low
      performing physicians over a 4-year period. We used administrative claims data
      from a PPO health plan in Hawaii, which implemented a P4P program, and a PPO plan
      in the South, which did not implement a P4P program. The difference-indifference
      model was used to compare the quality scores between the two physician groups in
      preventive measures, a heart failure measure, and an HbA1c testing measure. We
      found that P4P programs may be effective in incentivizing low performing
      physicians to improvement quality of care and sustain improvement, and the
      positive benefit of the P4P program may not be realized until the 3rd or 4th year
      of the program.

PMID- 20151588
TI  - Framing change for high-value healthcare systems.
AB  - Healthcare providers are challenged by forces that are driving change at an
      accelerated rate. Unfortunately, organizational structures, system inertia, and
      the lack of shared values in many organizations thwart change. Systems that do
      not understand the principles of change management for complex adaptive systems
      (CAS) continue to apply change models that have little chance of success. An
      understanding of the principles and actions that enable change in CAS and the use
      of a formal process to frame and focus change are essential for long-term
      success.

PMID- 20151589
TI  - Value management: optimizing quality, service, and cost.
AB  - Hospitals have wrestled with balancing quality, service, and cost for years--and
      the visibility and urgency around measuring and communicating real metrics has
      grown exponentially in the last decade. However, even today, most hospital
      leaders cannot articulate or demonstrate the "value" they provide to patients and
      payers. Instead of developing a strategic direction that is based around a core
      value proposition, they focus their strategic efforts on tactical decisions like
      physician recruitment, facility expansion, and physician alignment. In the
      healthcare paradigm of the next decade, alignment of various tactical initiatives
      will require a more coherent understanding of the hospital's core value
      positioning. The authors draw on their experience in a variety of healthcare
      settings to suggest that for most hospitals, quality (i.e., clinical outcomes and
      patient safety) will become the most visible indicator of value, and introduce a
      framework to help healthcare providers influence their value positioning based on
      this variable.

PMID- 20151590
TI  - Predictors of physician satisfaction among electronic health record system users.
AB  - Electronic health records (EHRs) have experienced slow adoption rates but play an
      important role in improving ambulatory quality of care. Sustained use of EHRs is
      closely related to physician satisfaction, however little research exists on this
      issue. We focused on physician EHR users to determine factors that are related to
      satisfaction with the level of computerization in their office practice. After
      controlling for various factors, physicians with more robust EHRs, and those who
      adopted their system two or more years ago, were more likely to be satisfied.
      Lastly, several individual EHR functionalities were independently related to
      improved satisfaction.

PMID- 20151591
TI  - Provider-initiated pay-for-performance in a clinically integrated hospital
      network.
AB  - Long Island Health Network developed a provider-initiated pay-for-performance (PI
      PFP) program beginning in 2004 and operated by 10 clinically integrated
      hospitals. The PI-PFP administrative processes, length of stay, patient
      satisfaction, and Hospital Quality Alliance measures are elaborated. PI-PFP has
      evolved over time and supports best practice sharing. We document how the risk
      amount is determined and then allocated to the Network and the individual
      hospitals based on performance, and we quantify the success of the program in
      achieving the goal of improved performance. A PI-PFP can prepare physicians and
      management for pay-for-performance or value-based purchasing programs operated by
      payers. Being self-administered, such a program can go beyond payer-run programs
      to focus attention on issues that are considered important by the hospitals and
      medical staffs, and that may not be feasible to measure or to include in a
      mandatory payer-run program.

PMID- 20151592
TI  - Pay-for-performance in dentistry: what we know.
AB  - Little is known about the effect of a pay-for-performance system (P4P) on primary
      medical care providers and even less is known about its potential impact in
      dentistry. Based on the growing acceptance of performance-based reimbursements in
      medicine and the dissemination of innovative technologies, structures, and
      processes of care from medical to dental services, it is likely that the dental
      profession will face performance-based payments in the not-too-distant future. In
      this paper, we present the current experience of P4P in primary medical care that
      has relevance to dentistry and discuss the dental performance-based programs to
      date. Taking into consideration these lessons, the structure of dental service
      delivery in the United States, and the paucity of evidence-based quality
      indicators in dentistry, we provide several guidelines for the design of P4P
      pilot programs for dental services. We conclude that large-scale implementation
      of P4P for dentistry may not be a realistic option before significant progress is
      achieved in quality of dental care indicators.

PMID- 20151593
TI  - Lead-time reduction utilizing lean tools applied to healthcare: the inpatient
      pharmacy at a local hospital.
AB  - The healthcare arena, much like the manufacturing industry, benefits from many
      aspects of the Toyota lean principles. Lean thinking contributes to reducing or
      eliminating nonvalue-added time, money, and energy in healthcare. In this paper,
      we apply selected principles of lean management aiming at reducing the wasted
      time associated with drug dispensing at an inpatient pharmacy at a local
      hospital. Thorough investigation of the drug dispensing process revealed
      unnecessary complexities that contribute to delays in delivering medications to
      patients. We utilize DMAIC (Define, Measure, Analyze, Improve, Control) and 5S
      (Sort, Set-in-order, Shine, Standardize, Sustain) principles to identify and
      reduce wastes that contribute to increasing the lead-time in healthcare
      operations at the pharmacy understudy. The results obtained from the study
      revealed potential savings of > 45% in the drug dispensing cycle time.

PMID- 20151594
TI  - [Retrospective analysis of occupational morbidity in agricultural workers of
      Bashkortostan Republic].
AB  - The authors analyzed occupational morbidity changes in agricultural workers of
      Bashkortostan Republic over 1997 2006, in relation to occupation, sex, age,
      length of service, work conditions and type. Findings are signs of elevated
      occupational morbidity level. Criteria of occupational risk for agricultural
      workers are specified.

PMID- 20151595
TI  - [Evaluating osteoporosis in occupations with vibration jeopardy in connection
      with climate and geographic features].
AB  - The article covers complex clinical and laboratory study in 140 workers with
      mining occupations in relation to climate and geographic location of the
      industrial enterprises. The examinees received ultrasound densitometry, X ray
      study of bone tissue, bone resorption and osteogenesis markers examination. All
      observations reliably demonstrated manifestations of osteopenic syndrome in
      workers engaged into the studied industrial branches.

PMID- 20151596
TI  - [Risk factors for metabolic syndrome in workers exposed to vibration].
AB  - The study covered prevalence of metabolic syndrome and its risk factors among
      mining and machinery industry workers. Reliably higher incidence of metabolic
      syndrome was revealed in workers exposed to vibration, when compared with the
      reference group. The authors calculated relative risk of metabolic syndrome
      development after exposure to the factor studied.

PMID- 20151597
TI  - [Biochemical markers of vibration effects in workers, and their criterial
      evaluation].
AB  - The authors studied influence of vibration on some serum biochemical values.
      Oxidative stress and muscular tissue parameters appeared to be the earliest
      indicators to change. Preclinical stage of vibration disease is characterized by
      lower activity of superoxide dismutase, increased urinary levels of creatinine
      and CCr coefficient. Slight increase in serum catalase activity is seen. These
      parameters increase in vibration disease patients. Urinary creatinine level
      remains high in some individuals with residual manifestations of vibration
      disease, after the exposure. Serum levels of copper, ceruloplasmin, potassium,
      sodium, cholinesterase activity are changed insignificantly under influence of
      vibration. The authors calculated occurrence of individuals who demonstrate
      abnormal changes of the stated parameters.

PMID- 20151598
TI  - [Criterial parameter of hygienic regulation for exposure to rarely repeated
      ultrashort electromagnetic impulses].
AB  - The authors justified an estimated induced current density as a criterial
      parameter for hygienic regulation of exposure to rarely repeated ultrashort
      electromagnetic impulses of nanosecond duration in electrical discharge devices
      applied in scientific research. The authors defined a threshold for harmful
      effects of the impulse, set maximal allowable levels of exposure for the devices
      operators. Methodic and regulatory documents were specified and approved to
      provide electromagnetic safety for personnel working in impulse fields.

PMID- 20151599
TI  - [Medical and social aspects of deafness at able bodied age].
AB  - Findings are that annual incidence of neurosensory deafness in Russia equals at
      most 0.06% of workers exposed to increased noise level at work and fails to
      demonstrate actual occupational risk of noise related diseases. The author proved
      that low level of neurosensory deafness diagnosis is caused not only by
      insatisfactory quality of periodic medical examinations, but also by psychosocial
      factors as fear of losing the job and negative attitude of social groups to
      people with impaired hearing. Essential arterial hypertension appeared to be
      highly prevelent among civil aviation crew members with neurosensory deafness.

PMID- 20151600
TI  - [Comparative evaluation of heat state in workers exposed to heating microclimate
      during cold and warm seasons].
AB  - The authors demonstrated differences in heat state among workers exposed to
      heating microclimate during cold and warm seasons. Same external thermal load in
      cold season induces more humidity loss, lower weighted average skin temperature,
      higher pulse rate, increased systolic and diastolic blood pressure. With that,
      heat discomfort was more in cold season, than in warm one, this necessitates
      decrease of thermal load in cold season vs. the warm one.

PMID- 20151601
TI  - [Experience with using mathematic model for evaluation of a posteriori
      occupational risk].
AB  - The author analyzed changes in occupational morbidity among workers of leading
      economic branches of Russian Federation, gave prognosis of occupational morbidity
      level for recent and distant future. The morbidity level is characterized by
      reliable decreasing trend--that is due to long decline in diagnostic rate of
      occupational diseases in periodic medical examinations. The author specified
      mathematic model to evaluate a posteriori occupational risk, based on materials
      concerning periodic medical examinations in coal miners.

PMID- 20151602
TI  - [Clinical peculiarities and treatment of toxic hepatitis (review of literature)].

PMID- 20151603
TI  - [Moscow declaration on diabetes and well being at work].

PMID- 20151604
TI  - What's new in paediatric conscious sedation in dentistry?

PMID- 20151605
TI  - Development of a UK version of CARL: a computer program for conducting exposure
      therapy for the treatment of dental injection fear.

PMID- 20151606
TI  - The safety and efficacy of intranasal midazolam sedation combined with inhalation
      sedation with nitrous oxide and oxygen in paediatric dental patients as an
      alternative to general anaesthesia.
AB  - INTRODUCTION: Conscious Decision' was published in 2000 by the Department of
      Health, effectively ending the provision of dental general anaesthesia (DGA)
      outside the hospital environment. Other aspects of dental anxiety and behavioural
      management and sedation techniques were encouraged before the decision to refer
      for a DGA was reached. Although some anxious children may be managed with
      relative analgesia (RA), some may require different sedation techniques for
      dentists to accomplish dental treatment. Little evidence has been published in
      the UK to support the use of alternative sedation techniques in children. This
      paper presents another option using an alternative conscious sedation technique.
      AIM: to determine whether a combination of intranasal midazolam (IN) and
      inhalation sedation with nitrous oxide and oxygen is a safe and practical
      alternative to DGA. STUDY DESIGN: A prospective clinical audit of 100 cases was
      carried out on children referred to a centre for DGA. METHOD: 100 children
      between 3 and 13 years of age who were referred for DGA were treated using this
      technique. Sedation was performed by intranasal midazolam followed by titrating a
      mixture of nitrous oxide and oxygen. A range of dental procedures was carried out
      while the children were sedated. Parents were present during the dental
      treatment. Data related to the patient, dentistry and treatment as well as
      sedation variables were collected at the treatment visit and a telephonic post
      operative assessment from the parents was completed a week later. RESULTS: It was
      found that 96% of the required dental treatment was completed successfully using
      this technique, with parents finding this technique acceptable in 93% of cases.
      50% of children found the intranasal administration of the midazolam acceptable.
      There was no clinically relevant oxygen desaturation during the procedure.
      Patients were haemodynamically stable and verbal contact was maintained
      throughout the procedure. CONCLUSIONS: In selected cases this technique provides
      a safe and effective alternative to DGA and could reduce the number of patients
      referred to hospitals for DGA. It is recommended that this technique should only
      be used by dentists skilled in sedation with the appropriate staff and equipment
      at their disposal.

PMID- 20151607
TI  - Is nitrous oxide a safe agent to use in conscious sedation for dentistry?

PMID- 20151609
TI  - Nitrous oxide analgesia in dentistry--training course at the Aga Khan University
      in Karachi, Pakistan.

PMID- 20151610
TI  - Interview with Nigel Robb President of SAAD. Interview by Derek Debuse.

PMID- 20151608
TI  - Propranolol and D-cycloserine as adjunctive medications in reducing dental fear
      in sedation practice.
AB  - Extensive research and clinical experience have demonstrated the usefulness of
      sedation in helping fearful patients receive dental treatment, particularly when
      they have urgent treatment needs. In addition, the efficacy of behavioural
      programmes for managing dental fears is well established. While often these two
      approaches are seen as oppositional, our work in Seattle, Morgantown and at
      King's College London Dental Institute demonstrates the complementarity of the
      two approaches. Using the example of two compounds, one very familiar,
      propranolol, and one that has recently become of interest, D-cycloserine, we wish
      to illustrate the manner in which these medications can be used to enhance
      behavioural approaches to managing dental anxiety.

PMID- 20151611
TI  - Mentoring for intravenous sedation in the rural north east of Scotland--a
      personal view.

PMID- 20151612
TI  - Secretary's correspondence.

PMID- 20151614
TI  - Models of teaching learning process: application in nursing.

PMID- 20151613
TI  - Medication non-compliance and substance abuse in schizophrenia.

PMID- 20151615
TI  - Effectiveness of planned teaching programme regarding management of BPH on BPH
      patients.

PMID- 20151616
TI  - What's new with upper respiratory infections?

PMID- 20151617
TI  - This issue: upper respiratory tract infections.

PMID- 20151618
TI  - A 9-year-old girl who was wheezing for 3 months.

PMID- 20151619
TI  - A 6-year-old girl with brown papules on her chest.

PMID- 20151620
TI  - Croup: common syndromes and therapy.

PMID- 20151621
TI  - Pharyngitis and streptococcal throat infections.

PMID- 20151622
TI  - Update: acute otitis media.

PMID- 20151623
TI  - Acute sinusitis: clinical manifestations and treatment approaches.

PMID- 20151624
TI  - Chronic sinusitis in children.

PMID- 20151625
TI  - Crossing the threshold of cancer and aging: integrating gerontological and
      oncological nursing knowledge and skills.

PMID- 20151629
TI  - Bases and basic materials in chemical and environmental processes. Liquid versus
      solid basicity.

PMID- 20151627
TI  - Evidence-based guideline. Wandering.

PMID- 20151630
TI  - Lanthanide luminescence for biomedical analyses and imaging.

PMID- 20151631
TI  - Stability and aggregation of metal oxide nanoparticles in natural aqueous
      matrices.
AB  - There is a pressing need for information on the mobility of nanoparticles in the
      complex aqueous matrices found in realistic environmental conditions. We
      dispersed three different metal oxide nanoparticles (TiO(2), ZnO and CeO(2)) in
      samples taken from eight different aqueous media associated with seawater,
      lagoon, river, and groundwater, and measured their electrophoretic mobility,
      state of aggregation, and rate of sedimentation. The electrophoretic mobility of
      the particles in a given aqueous media was dominated by the presence of natural
      organic matter (NOM) and ionic strength, and independent of pH. NOM adsorbed onto
      these nanoparticles significantly reduces their aggregation, stabilizing them
      under many conditions. The transition from reaction to diffusion limited
      aggregation occurs at an electrophoretic mobility from around -2 to -0.8 microm
      s(-1) V(-1) cm. These results are key for designing and interpreting nanoparticle
      ecotoxicity studies in various environmental conditions.

PMID- 20151632
TI  - Environmental Management System (ISO 14001) certification in developing
      countries: challenges and implementation strategies.

PMID- 20151633
TI  - Comment on "Unlike PAHs from Exxon Valdez crude oil, PAHs from Gulf of Alaska
      coals are not readily bioavailable".

PMID- 20151635
TI  - Simulation of UV photoreactor for degradation of chemical contaminants: model
      development and evaluation.
AB  - Models simulating the performance of UV reactors enhance our understanding of the
      fundamental principles governing the operation of these units. When modeling the
      performance of UV reactors, governing equations for all related phenomena are
      derived and solved. This research presents a step-by-step methodology to setup
      and solve the governing equations determining the performance of UV reactors and
      to evaluate the results. A computational fluid dynamic (CFD) model was developed
      in order to simulate UV photoreactors in the Eulerian framework for chemical
      removal using a UV-based hydroxyl radical initiated oxidation process. Verifying
      the results of the integrated CFD model, a novel method was developed using a
      modified planar laser-induced fluorescence technique for measuring tracer
      concentration profiles inside the UV reactor. In addition, the components of the
      CFD model--hydrodynamics and radiation--were evaluated using experimental profile
      throughout the entire reactor. This verified procedure can be applied to the
      simulation and optimization of UV photoreactors with various geometries and
      operating conditions.

PMID- 20151636
TI  - Gypsum scaling and cleaning in forward osmosis: measurements and mechanisms.
AB  - This study investigates gypsum scaling and cleaning behavior in forward osmosis
      (FO). The results show that gypsum scaling in FO is almost fully reversible, with
      more than 96% recovery of permeate water flux following a water rinse without
      addition of chemical cleaning reagents. Parallel comparisons of fouling and
      cleaning were made between FO (without hydraulic pressure) and RO (under high
      hydraulic pressure) modes. The shape of the water flux decline curves during
      gypsum scaling is similar in the two modes, but the flux recovery in FO mode is
      higher than that in RO mode by about 10%. This behavior suggests that operating
      in FO mode may reduce the need for chemical cleaning. The role of membrane
      materials in controlling gypsum scaling and cleaning was investigated using
      cellulose acetate (CA) and polyamide (PA) membranes. Gypsum scaling of PA
      membranes causes more severe flux decline and is harder to clean than that of CA
      membranes. AFM force measurements were performed between a gypsum particle probe
      and the membrane surfaces to elucidate gypsum scaling mechanisms. Analysis of
      adhesion force data indicates that gypsum scaling of the PA membrane is dominated
      by heterogeneous/surface crystallization, while gypsum scaling of the CA membrane
      is dominated by bulk crystallization and subsequent particle deposition.This
      finding implies that membrane surface modification and new material development
      can be an effective strategy to mitigate membrane scaling.

PMID- 20151637
TI  - Phenylacetylene one-dimensional nanostructures on the Si(100)-2 x 1:H surface.
AB  - Using ultrahigh vacuum (UHV) scanning tunneling microscopy (STM), many olefins
      have been shown to self-assemble on the hydrogen-passivated Si(100)-2 x 1 surface
      into one-dimensional nanostructures. This paper demonstrates that similar one
      dimensional nanostructures can also be realized using alkynes. In particular, UHV
      STM, sum frequency generation (SFG), and density functional theory (DFT) are
      employed to study the growth mechanism and binding configuration of
      phenylacetylene (PA) one-dimensional nanostructures on the Si(100)-2 x 1:H
      surface. Molecular-resolution UHV STM images reveal the binding position and
      spacing of PA with respect to the underlying silicon dimer rows. Furthermore, UHV
      STM characterization of heteromolecular one-dimensional nanostructures of styrene
      and PA shows distinct electronic contrast between the two molecules, which is
      confirmed using simulated STM images derived from DFT and provides insight into
      the nature of PA binding to silicon. Additional evidence from SFG measurements
      corroborates the conclusion that the terminal carbon atoms of PA retain pi
      conjugation following reaction to the Si(100)-2 x 1:H surface.

PMID- 20151638
TI  - Integrated in silico-in vitro strategy for addressing cytochrome P450 3A4 time
      dependent inhibition.
AB  - Throughout the past decade, the expectations from the regulatory agencies for
      safety, drug-drug interactions (DDIs), pharmacokinetic, and disposition
      characterization of new chemical entities (NCEs) by pharmaceutical companies
      seeking registration have increased. DDIs are frequently assessed using in
      silico, in vitro, and in vivo methodologies. However, a key gap in this screening
      paradigm is a full structural understanding of time-dependent inhibition (TDI) on
      the cytochrome P450 systems, particularly P450 3A4. To address this, a number of
      high-throughput in vitro assays have been developed. This work describes an
      automated assay for TDI using two concentrations at two time points (2 + 2
      assay). Data generated with this assay for over 2000 compounds from multiple
      therapeutic programs were used to generate in silico Bayesian classification
      models of P450 3A4-mediated TDI. These in silico models were validated using
      several external test sets and multiple random group testing (receiver operator
      curve value >0.847). We identified a number of substructures that were likely to
      elicit TDI, the majority containing indazole rings. These in vitro and in silico
      approaches have been implemented as a part of the Pfizer screening paradigm. The
      Bayesian models are available on the intranet to guide synthetic strategy,
      predict whether a NCE is likely to cause a TDI via P450 3A4, filter for in vitro
      testing, and identify substructures important for TDI as well as those that do
      not cause TDI. This represents an integrated in silico-in vitro strategy for
      addressing P450 3A4 TDI and improving the efficiency of screening.

PMID- 20151639
TI  - Synthesis and uptake of fluorescence-labeled Combi-molecules by P-glycoprotein
      proficient and -deficient uterine sarcoma cells MES-SA and MES-SA/DX5.
AB  - Here, we report on the first synthesis of fluorescent-labeled epidermal growth
      factor receptor-DNA targeting combi-molecules, and we studied the influence of P
      glycoprotein status of human sarcoma MES-SA cells on their growth inhibitory
      effect and cellular uptake. The results showed that 6, bearing a longer spacer
      between the quinazoline ring and the dansyl group, was more stable and more
      cytotoxic than 4. In contrast to the latter, it induced significant levels of DNA
      damage in human tumor cells. Moreover, in contrast to doxorubicin, a drug known
      to be actively effluxed by P-gp, the more stable combi-molecule 6 induced almost
      identical levels of drug uptake and DNA damage in P-gp-proficient and -deficient
      cells. Likewise, in contrast to doxorubicin, 4 and 6 exerted equal levels of
      antiproliferative activity against the two cell types. The results in toto
      suggest that despite their size, the antiproliferative effects of 4 and 6 were
      independent of P-gp status of the cells.

PMID- 20151640
TI  - High-resolution differential ion mobility separations using helium-rich gases.
AB  - Analyses of complex mixtures and characterization of ions increasingly involve
      gas-phase separations by ion mobility spectrometry (IMS) and particularly
      differential or field asymmetric waveform IMS (FAIMS) based on the difference of
      ion mobility in strong and weak electric fields. The key advantage of FAIMS is
      substantial orthogonality to mass spectrometry (MS), which makes FAIMS/MS hybrid
      a powerful analytical platform of broad utility. However, the potential of FAIMS
      has been constrained by limited resolution. Here, we report that the use of gas
      mixtures comprising up to 75% He dramatically increases the FAIMS separation
      capability, with the resolving power for peptides and peak capacity for protein
      digests reaching and exceeding 100. The resolution gains extend to small
      molecules, where previously unresolved isomers can now be separated. These
      performance levels open major new applications of FAIMS in proteomic and other
      biomolecular analyses.

PMID- 20151641
TI  - Gas-phase thermolysis of a guanidinate precursor of copper studied by matrix
      isolation, time-of-flight mass spectrometry, and computational chemistry.
AB  - The fragmentation of the copper(I) guanidinate [Me(2)NC(NiPr)(2)Cu](2) (1) has
      been investigated with time-of-flight mass spectrometry (TOF MS), matrix
      isolation FTIR spectroscopy (MI FTIR spectroscopy), and density functional theory
      (DFT) calculations. Gas-phase thermolyses of 1 were preformed in the temperature
      range of 100-800 degrees C. TOF MS and MI FTIR gave consistent results, showing
      that precursor 1 starts to fragment at oven temperatures above 150 degrees C,
      with a close to complete fragmentation at 260 degrees C. Precursor 1 thermally
      fragments to Cu((s)), H(2)(g), and the oxidized guanidine
      Me(2)NC(=NiPr)(N=CMe(2)) (3). In TOF MS experiment, 3 was clearly indentified by
      its molecular ion at 169.2 u. Whereas H(2)(+) was detected, atomic Cu was not
      found in gas-phase thermolysis. In addition, the guanidine Me(2)NC(NiPr)(NHiPr)
      (2) was detected as a minor component among the thermolysis products. MI
      thermolysis experiments with precursor 1 were performed, and species evolving
      from the thermolysis oven were trapped in solid argon at 20 K. These species were
      characterized by FTIR spectroscopy. The most indicative feature of the resulting
      spectra from thermolysis above 150 degrees C was a set of intense and structured
      peaks between 1600 and 1700 cm(-1), an area where precursor 1 does not have any
      absorbances. The guanidine 2 was matrix-isolated, and a comparison of its FTIR
      spectrum with the spectra of the thermolysis of 1 indicated that species 2 was
      among the thermolysis products. However, the main IR bands in the range of 1600
      and 1700 cm(-1) appeared at 1687.9, 1668.9, 1635.1, and 1626.6 cm(-1) and were
      not caused by species 2. The oxidized guanidine 3 was synthesized for the first
      time and characterized by (1)H NMR and FTIR spectroscopy. A comparison of an FTIR
      spectrum of matrix isolated 3 with spectra of the thermolysis of 1 revealed that
      the main IR bands in the range of 1600 and 1700 cm(-1) are due to the presence of
      3. The isomers exhibit the NMe(2) group cis or trans to the iPr group, with cis-3
      being significantly less stable than trans-3. At higher temperature secondary
      thermal fragments had been observed. For example at 700 degrees C, TOF MS and MI
      FTIR data showed that species 2 and 3 both eliminate HNMe(2) to give the
      carbodiimides iPrNCNiPr (CDI) and iPrNCN[C(=CH(2))Me] (4), respectively. A DFT
      study of the decomposition of compound 1 was undertaken at the B3LYP/6-31+G(d,p)
      level of theory employing dispersion-correcting potentials (DCPs). The DFT study
      rationalized both carbodiimide deinsertion and beta-hydrogen elimination as
      exergonic decomposition pathways (DeltaG = -44.4 kcal/mol in both cases), but
      experiment showed beta-hydrogen elimination to be the favorable route.

PMID- 20151642
TI  - Evaluation of [Ln(H2cmp)(H2O)] metal organic framework materials for potential
      application as magnetic resonance imaging contrast agents.
AB  - Aqueous suspensions of metal organic frameworks (MOF) containing different Ln(3+)
      ions, consisting of a series of layered Ln(3+) networks formulated as
      [Ln(H(2)cmp)(H(2)O)] (where H(5)cmp is (carboxymethyl)iminodi(methylphosphonic
      acid), with a relatively wide size distribution (400 nm to 1 microm) were studied
      by relaxometry. The water (1)H longitudinal (r(1)) and transverse (r(2))
      relaxivities were obtained for aqueous suspensions of these materials with
      different lanthanide ions. The values of r(1) are very small and varied only
      slightly with the effective magnetic moment (mu(eff)) of the lanthanide ions,
      while r(2) values are larger and proportional to the value of mu(eff)(2). The
      dependence of R(2) on tau(CP) (the time interval between two consecutive
      refocusing pulses in the train of 180 degrees pulses applied in a CPMG pulse
      sequence) was evaluated. The value of R(2) initially increases with tau(CP) and
      then saturates at higher tau(CP) at a value that is about 3 to 5 times lower than
      R(2p)*. This can be explained by the static dephasing regime (SDR) theory, in
      which the diffusion effect is taken into account and where the condition tau(D) >
      Delta omega(r(p))(-1) holds (tau(D) = r(p)(2)/D, where D is the diffusion
      coefficient, r(p) is the radius of the particle, and Delta omega(r(p)) is the
      Larmor frequency shift at the particle's surface). Separation of the particles
      into two fractions with different particle sizes led to a significant enhancement
      of the r(2) relaxivity of the smaller particles with a narrow size distribution.
      Magnetometric measurements performed with the particles containing Dy(III),
      Ho(III), and Gd(III) showed a typical paramagnetic behavior from 4 to 100 K, used
      to determine the Curie constants.

PMID- 20151643
TI  - Two- and three-dimensional open-framework uranium arsenates: synthesis,
      structure, and characterization.
AB  - Hydrothermal reactions between uranium salts and arsenic pentoxide in the
      presence of two different amines yielded six new uranium arsenate phases
      exhibiting open-framework structures, ethylenediamine (en):
      [C(2)N(2)H(9)][(UO(2))(AsO(4))], I; [C(2)N(2)H(10)][(UO(2))F(HAsO(4))](2) x 4
      H(2)O, II; [C(2)N(2)H(9)][U(2)F(5)(HAsO(4))(2)], III;
      [C(2)N(2)H(9)][UF(2)(AsO(4))], IV; diethylenetriamine (DETA),
      [C(4)N(3)H(16)][U(2)F(3)(AsO(4))(2)(HAsO(4))], V; and
      [C(4)N(3)H(16)][U(2)F(6)(AsO(4))(HAsO(4))], VI. The structures were determined
      using single crystal studies, which revealed two- (I, II, V) and three
      dimensional (III, IV, VI) structures for the uranium arsenates. The uranium atom,
      in these compounds, exhibits considerable variations in the coordination (6 to 9)
      that appears to have some correlation with the synthetic conditions. The water
      molecules in [C(2)N(2)H(10)][(UO(2))F(HAsO(4))](2) x 4 H(2)O, II, could be
      reversibly removed, and the dehydrated phase,
      [C(2)N(2)H(10)][(UO(2))F(HAsO(4))](2), IIa, was also characterized using single
      crystal studies. The observation of many mineralogical structures in the present
      compounds suggests that the hydrothermal method could successfully replicate the
      geothermal conditions. As part of this study, we have observed autunite,
      Ca[(UO(2))(PO(4))](2)(H(2)O)(11), metavauxite,
      [Fe(H(2)O)(6)][Al(OH)(H(2)O)(PO(4))](2), linarite, PbCu(SO(4))(OH)(2), and
      tancoite, LiNa(2)H[Al(PO(4))(2)(OH)], structures. The repeated observation of the
      secondary building unit, SBU-4, in many of the uranium arsenate structures
      suggests that these are viable building units. Optical studies on the uranium
      arsenate compound, [C(4)N(3)H(16)][U(2)F(6)(AsO(4))(HAsO(4))], VI, containing
      uranium in the +4 oxidation state indicates a blue emission through an
      upconversion process. The compound also exhibits antiferromagnetic behavior.

PMID- 20151644
TI  - Bifunctional asymmetric catalysis: amplification of Bronsted basicity can
      orthogonally increase the reactivity of a chiral Bronsted acid.
AB  - The reactivity of a series of symmetrical chiral Bronsted acids (polar ionic
      hydrogen-bond donors) follows the counterintuitive trend wherein the more
      Bronsted basic member is a more effective catalyst for the aza-Henry (nitro
      Mannich) reaction. This new design element leads to a substantially more reactive
      catalyst for the aza-Henry reaction, one that can promote the addition of a
      secondary nitroalkane. Additionally, when an achiral Bronsted acid (TfOH) is used
      in slight excess of the neutral, chiral bisamidine ligand, diastereoselection can
      be optimized to levels generally greater than 15:1 while the enantioselection
      remains unchanged at generally >90% ee.

PMID- 20151645
TI  - Comment on "Mechanistic investigations on the Belousov-Zhabotinsky reaction with
      oxalic acid substrate. 2. Measuring and modeling the oxalic acid-bromine chain
      reaction and simulating the complete oscillatory system".

PMID- 20151647
TI  - Persistence of polybrominated diphenyl ethers in agricultural soils after
      biosolids applications.
AB  - This study examines polybrominated diphenyl ethers (PBDE) levels, trends in
      biosolids from a wastewater treatment plant, and evaluates potential factors
      governing PBDE concentrations and the fate in agricultural soils fertilized by
      biosolids. The mean concentration of the most abundant PBDE congeners in
      biosolids ( summation operatorBDE-47, BDE-99, and BDE-209) generated by one
      wastewater treatment plant was 1250 +/- 134 microg/kg d.w. with no significant
      change in concentration over 32 months (n = 15). In surface soil samples from the
      Mid-Atlantic region, average PBDE concentrations in soil from fields receiving no
      biosolids (5.01 +/- 3.01 microg/kg d.w.) were 3 times lower than fields receiving
      one application (15.2 +/- 10.2 microg/kg d.w.) and 10 times lower than fields
      that had received multiple applications (53.0 +/- 41.7 microg/kg d.w.). The
      cumulative biosolids application rate and soil organic carbon were correlated
      with concentrations and persistence of PBDEs in soil. A model to predict PBDE
      concentrations in soil after single or multiple biosolids applications provides
      estimates which fall within a factor of 2 of observed values.

PMID- 20151648
TI  - Influence of the input system (conventional versus organic farming) on metabolite
      profiles of maize ( Zea mays ) kernels.
AB  - Maize ( Zea mays ) kernels grown conventionally and organically, respectively,
      were investigated using a gas chromatography/mass spectrometry (GC/MS)-based
      metabolite profiling methodology. By analysis of three cultivars grown at two
      locations with different input systems and at a third location where both organic
      and conventional farming were applied, the impact of the growing regime on the
      metabolite spectrum should be put into the context of natural variability. The
      applied analytical approach involved consecutive extraction of freeze-dried maize
      flour and subsequent subfractionation. Approximately 300 compounds from a broad
      spectrum of chemical classes were detected, of which 167 were identified. The
      metabolite profiling data were statistically assessed via principal component
      analysis (PCA) and analysis of variance (ANOVA). The PCA demonstrated that the
      observed separations were mainly due to genetic differences (cultivars) and
      environmental influences. The different input systems (conventional/organic) only
      led to minor differentiations. ANOVA and quantification of selected constituents
      confirmed these observations. Only three metabolites (malic acid, myo-inositol,
      and phosphate) were consistently different because of the employed input system
      if samples from all field trials were considered.

PMID- 20151649
TI  - Gallic acid induces apoptosis of lung fibroblasts via a reactive oxygen species
      dependent ataxia telangiectasia mutated-p53 activation pathway.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder
      characterized by the activation of fibroblasts and the overproduction of
      extracellular matrix. Fibroblast resistance to apoptosis leads to increased
      fibrosis. Targeting fibroblasts with apoptotic agents represents a major
      therapeutic intervention for debilitating IPF. Gallic acid (3,4,5
      trihydroxybenzoic acid), a naturally occurring plant phenol, has been reported to
      induce apoptosis in tumor cell lines and renal fibroblasts. However, the effects
      of gallic acid on lung fibroblasts have not been investigated. The aim of the
      present study is to determine the effects of gallic acid on primary cultured
      mouse fibroblasts. Our results showed that gallic acid induces the apoptotic
      death of fibroblasts via both intrinsic and extrinsic apoptotic pathways by the
      elevation of PUMA, Fas, and FasL protein levels. Moreover, intracellular reactive
      oxygen species (ROS) generation and 8-hydroxy-2'-deoxyguanosine production were
      observed in gallic acid-stimulated fibroblasts. Mechanistic studies showed that
      gallic acid induces early phosphorylation of p53(Ser18) and histone 2AX(Ser139)
      (H2AX) via ataxia telangiectasia mutated (ATM) activation in response to ROS
      provoked DNA damage. When mouse lung fibroblasts were treated with caffeine, an
      ATM kinase inhibitor, the levels of p53, phosphorylated p53(Ser18), and cell
      death induced by gallic acid were significantly attenuated. Additionally,
      pretreatment with antioxidants drastically inhibited the gallic acid-induced 8
      hydroxy-2'-deoxyguanosine (8-OH-dG) formation and phosphorylation of p53(Ser18)
      and ATM(Ser1981), as well as apoptosis. Our results provide the first evidence of
      the activation of ROS-dependent ATM/p53 signaling as a critical mechanism of
      gallic acid-induced cell death in primary cultured mouse lung fibroblasts.

PMID- 20151650
TI  - Counting the atoms in supported, monolayer-protected gold clusters.
AB  - Mass spectrometry of supported, monolayer-protected, nominally Au(38) (MP-Au(38))
      clusters is performed via quantitative High Angle Annular Dark Field-Scanning
      Transmission Electron Microscopy (HAADF-STEM) using size-selected Au(N) clusters
      (N = 25, 38, 55) as mass standards. With the intensity due to the (presumed) 24
      hexanethiolate ligands taken into account, the clusters are found to contain 38
      +/- 2 Au atoms. The method may also be used to determine the degree of
      aggregation of deposited nanoparticles.

PMID- 20151651
TI  - Synthesis and fungicidal activity of aryl carbamic acid-5-aryl-2-furanmethyl
      ester.
AB  - Chitin, a major structural component of insect cuticle and fungus cell wall but
      absent in plants and vertebrates, is regarded as a safe and selective target for
      pest control agents. Chitin synthesis inhibitors (CSIs) have been well-known as
      insect growth regulators (IGRs) but rarely found as fungicides in agriculture. To
      find novel CSIs with good activity, benzoylphenylurea, a typical kind of CSIs,
      was chosen as the lead compound and 26 novel aryl carbamic acid-5-aryl-2
      furanmethyl esters were designed by converting the urea linkages of
      benzoylphenylureas to carbamic acid esters and changing the aniline parts into
      furanmethyl groups. The title compounds were synthesized and their structures
      confirmed by IR, (1)H NMR, and elemental analysis. Preliminary insecticidal and
      fungicidal bioassays were carried out. The results indicated that the title
      compounds had no insecticidal effect on Culex pipiens pallens and Plutella
      xylostella Linnaeus , but most compounds exhibited good fungicidal activities
      against Corynespora cassiicola , Thanatephorus cucumeris , Botrytis cinerea , and
      Fusarium oxysporum . In particular, compounds V-4, V-6, V-7, and V-8 showed
      better activities against the four strains than those of the commercialized
      fungicides. The morphologic result suggested that compound V-21 had disturbed the
      cell wall formation of C. cassiicola. The results indicated that modification on
      the urea linkage of benzoylphenylurea was an effective way to discover new
      candidates for fungicides.

PMID- 20151652
TI  - Discrimination of farm waste contamination by fluorescence spectroscopy coupled
      with multivariate analysis during a biodegradation study.
AB  - The persistence of potential tracers of dissolved organic matter (DOM) generated
      from farm waste-amended soil was investigated by fluorescence spectroscopy
      coupled with classification and regression tree (CART) and principal component
      analysis (PCA) during a short-term (8 days) to midterm (60 days) biodegradation
      study. Pig manure (PM), cow manure (CM), wheat straw (WS), and soil alone (SA)
      treatment inputs were used. Waste amendments were potential sources of higher DOM
      concentrations. PCA revealed the DOM quality differences between farm wastes and
      soil alone as well as a significant shift observed from the biochemical to the
      geochemical fluorescent fraction in SA and PM treatments. The tryptophan:Humic
      Like ratio and tryptophan zone were the potential discriminators of recent and
      midterm pollution by farm wastes. Integral intensities of the Fulvic-Like zone
      and region III discriminated the PM from CM and WS during the 60 days. CART
      analysis showed 90 and 100% potential for farm wastes discrimination from soil
      during P1 and P2, respectively. The prediction successes were 72 and 57% for PM
      from other wastes and 60 and 100% for WS during both periods. Fluorescence
      spectroscopy in combination with CART analysis can be a nondestructive innovative
      method for monitoring susceptible farm waste contamination.

PMID- 20151653
TI  - Synthesis of temperature responsive poly(N-isopropylacrylamide) using ultrasound
      irradiation.
AB  - Ultrasound was employed to synthesize poly(N-isopropylacrylamide) [poly(NIPAM)]
      either as aqueous solutions or microgels in the absence of a chemical initiator.
      Poly(NIPAM) of different microstructures can be readily prepared via ultrasound
      irradiation by varying the reaction temperature. At a preparation temperature of
      20 degrees C, poly(NIPAM) was formed in aqueous solutions, whereas, at a higher
      preparation temperature (beyond the lower critical solution temperature of
      approximately 32 degrees C), poly(NIPAM) microgels were formed. In addition, the
      high shear gradients generated by the acoustic cavitation process aid to control
      or vary the molecular weights of poly(NIPAM) formed in aqueous solutions. The
      swelling behavior of poly(NIPAM) at different concentrations of sodium dodecyl
      sulfate (SDS) was also studied. An increase in the transition temperature and
      hydrodynamic size of the particles was attributed to SDS binding to the polymer
      network through hydrophobic interactions. Light scattering data reflected the
      formation of larger microgels at low cross-linker concentrations. The
      encapsulation of rhodamine B within the microgels was achieved by sonicating the
      monomer containing the dye. The subsequent release of the dye was consistent with
      Fickian diffusion and the diffusion coefficient of the dye was estimated as 4.0 x
      10(-12) and 3.6 x 10(-11) m(2) s(-1) at 20 and 40 degrees C, respectively. From
      the diffusion coefficients, the viscosities of the polymer samples at 20 and 40
      degrees C were determined using the Stokes-Einstein equation to be 77 and 10 cP,
      respectively.

PMID- 20151654
TI  - A preliminary investigation of the additivity of pi-pi or pi+-pi stacking and T
      shaped interactions between natural or damaged DNA nucleobases and histidine.
AB  - Previous computational studies have examined pi-pi and pi(+)-pi stacking and T
      shaped interactions in nucleobase-amino acid dimers, yet it is important to
      investigate how additional amino acids affect these interactions since
      simultaneous contacts often appear in nature. Therefore, this paper investigates
      the geometries and binding strengths of amino acid-nucleobase-amino acid trimers,
      which are compared to the corresponding nucleobase-amino acid dimer interactions.
      We concentrate on systems containing the natural nucleobase adenine or its
      (cationic) damaged counterpart, 3-methyladenine, and the aromatic amino acid
      histidine, in both the neutral and protonated forms. This choice of molecules
      provides information about pi-pi and pi(+)-pi stacking and T-shaped interactions
      in asymmetric, biologically relevant systems. We determined that both stacked and
      T-shaped interactions, as well as both pi-pi and pi(+)-pi interactions, exhibit
      geometric additivity. To investigate the energetic additivity in our trimers, the
      synergy (E(syn)) and the additivity (E(add)) energy were examined. E(add) reveals
      that it is important to consider the interaction between the two amino acids when
      examining the additivity of nucleobase-amino acid interactions. Additionally,
      E(syn) and E(add) indicate that pi(+)-pi interactions are quite different from pi
      pi interactions. The magnitude of E(add) is generally less than 2 kJ mol(-1),
      which suggests that these interactions are additive. However, the interaction
      energy analysis does not provide information about the individual interactions in
      the trimers. Therefore, the quantum theory of atoms in molecules (QTAIM) was
      implemented. We find inconsistent conclusions from our QTAIM analysis and
      interaction energy evaluation. However, the magnitudes of the differences between
      the dimer and trimer critical point properties are extremely small and therefore
      may not be able to yield conclusive descriptions of differences (if any) between
      the dimer and trimer interactions. We hypothesize that, due to the limited number
      of investigations of this type, it is currently unclear how QTAIM can improve our
      understanding of pi-pi and pi(+)-pi dimers and trimers. Therefore, future work
      must systematically alter the pi-pi or pi(+)-pi system to definitively determine
      how the geometry, symmetry, and system size alter the QTAIM analysis, which can
      then be used to understand biologically relevant complexes.

PMID- 20151655
TI  - 2,3-Bis(phenylsulfonyl)-1,3-butadiene as a reagent for the synthesis of the
      azatricyclic core of (+/-)-halichlorine.
AB  - An efficient stereocontrolled route to the azatricyclic core of an advanced
      halichlorine intermediate is described. Reaction of the oxime derived from 2-(oxo
      cyclopentyl)acetic acid ethyl ester with 2,3-bis(phenylsulfonyl)-1,3-butadiene
      gives rise to a 7-oxa-1-azanorbornane cycloadduct in high yield. The formation of
      the bicyclic isoxazolidine arises from conjugate addition of the oxime onto the
      diene to afford a transient nitrone that then undergoes an intramolecular dipolar
      cycloaddition. Treatment of the cycloadduct with 5% Na/Hg results in reductive
      nitrogen-oxygen bond cleavage to furnish a spirocyclic piperidinone, which was
      further elaborated to an advanced intermediate employed in an earlier synthesis
      of halichlorine.

PMID- 20151656
TI  - Kinetics of removal of carbon dioxide by aqueous solutions of N,N
      diethylethanolamine and piperazine.
AB  - N,N-Diethylethanolamine (DEEA) is a very promising absorbent for CO(2) removal
      from gaseous streams, as it can be prepared from renewable resources. Aqueous
      mixtures of DEEA and piperazine (PZ) are attractive for the enhancement of CO(2)
      capture, due to the high CO(2) loading capacity of DEEA and high reactivity of
      PZ. In the present work, for the first time, the equilibrium and kinetic
      characteristics of the CO(2) reaction with such mixtures were considered. Kinetic
      data were obtained experimentally, by using a stirred cell reactor. These data
      were interpreted using a homogeneous activation mechanism, by which the
      investigated reaction was considered as a reaction between CO(2) and DEEA in
      parallel with the reaction of CO(2) with PZ. It is found that, in the studied
      range of temperatures, 298-308 K, and overall amine concentrations, 2.1-2.5
      kmol/m(3), this reaction system belongs to the fast pseudo-first-order reaction
      regime systems. The second-order rate constant for the CO0 reaction with PZ was
      determined from the absorption rate measurements in the activated DEEA solutions,
      and its value at 303 K was found to be 24,450 m(3)/(kmol s).

PMID- 20151657
TI  - Heterogeneous reactions of methacrolein and methyl vinyl ketone on alpha-Al2O3
      particles.
AB  - The heterogeneous reactions of methacrolein (MAC) and methyl vinyl ketone (MVK)
      on alpha-Al(2)O(3) surfaces have been studied in a flow reactor using
      transmission-Fourier Transform Infrared (T-FTIR) spectroscopy to monitor the
      reaction progress. Unlike SiO(2) particles where MAC and MVK are weakly
      physisorbed, the results in this work demonstrate that on c-AlO3 particles MAC
      and MVK are irreversibly adsorbed and can rapidly react on the surface to form
      various products such as aldehydes, organic acids, hydrogen peroxide, and even
      higher molecular weight compounds. The initial uptake rates and initial uptake
      coefficients for MAC and MVK on alpha-Al(2)O(3) under dry conditions were
      determined to explore the reactivity of the particles. Furthermore, the effect of
      water vapor on the heterogeneous reactions was also investigated as a function of
      relative humidity. Both the heterogeneous uptake and transformation of MAC and
      MVK on alpha-Al(2)O(3) were largely suppressed under humid conditions due to the
      depletion of surface active sites by water molecules. On the basis of
      experimental results, atmospheric implications of heterogeneous reactions of MAC
      and MVK were discussed. Our work suggests that heterogeneous reactions on alpha
      Al(2)O(3) can be important sinks for MAC and MVK as well as possible contributors
      to atmospheric organic aerosol.

PMID- 20151658
TI  - Synthesis of 3,4,5-trisubstituted-1,2,4-triazoles.

PMID- 20151659
TI  - High-porosity macroporous polymers sythesized from titania-particle-stabilized
      medium and high internal phase emulsions.
AB  - Particle-stabilized high internal phase emulsions have been used to synthesize
      tough and very high porosity macroporus polymers with a closed-cell pore
      structure. In this study, we show that Pickering water-in-oil emulsion templates
      with up to an 85 vol % internal phase can be stabilized by only 1 wt % of titania
      particles with their surfaces suitably modified by the adsorption of 3.5 +/- 0.5
      wt % oleic acid. The pore structure and mechanical properties of the resulting
      macroporous polymers were tailored by altering the internal phase volume ratio of
      the emulsion template and the titania particle concentration used to stabilize
      the emulsion templates. The pore size and pore size distributions increase with
      increasing internal phase volume of the emulsion template as well as decreasing
      titania particle concentration used to stabilize the emulsion template. The
      mechanical properties, namely, Young's modulus and the crush strength of the
      macroporous polymers, increased with decreasing porosity and increasing foam
      density. The toughest macroporous polymer had the lowest porosity but also the
      smallest pore size and narrowest pore size distribution.

PMID- 20151660
TI  - Templated self-assembly of ZnO films on monolayer patterns with nanoscale
      resolution.
AB  - Lithographically defined self-growing ZnO films were prepared by a bioinspired
      chemical bath deposition technique (CBD). We observed a high selectivity of ZnO
      deposition: Teflon-like per-fluoro-decyl-trichlorosilane (FDTS) monolayers
      repelled ZnO primary particles, whereas amino-functionalized areas of the
      substrate were selectively covered by a highly anisotropic, oriented, and compact
      ZnO film with a thickness of 50 nm. The size of the primary particles in our
      methanol-based solution was approximately 2.5 nm. On the amino substrate they
      formed agglomerates not larger than 30 nm. Monolayer patterns made by polymer
      blend lithography were templated with an edge resolution of 30 nm. By using a
      specialized derivative of microcontact printing, we prepared layout-defined
      silane templates, which reliably determined the growth of a layout-defined,
      patterned oxide film with submicrometer lateral resolution.

PMID- 20151662
TI  - 100% efficient sub-nanoliter sample introduction in laser-induced breakdown
      spectroscopy and inductively coupled plasma spectrometry: implications for
      ultralow sample volumes.
AB  - Recently, nanoflow nebulizers with low-volume drain-free spray chambers became
      available for inductively coupled plasma-mass spectrometry application for
      analysis of very small sampling volumes. The present technical note reports on a
      different approach for 100% efficient subnanoliter sample introduction, the
      application of monodisperse piezoelectric microdroplet dispensers which generate
      40-50 microm droplets with high reproducibility if nozzles of 30 microm diameter
      are applied. The droplets having volumes below 0.1 nL can be introduced loss-free
      and without plasma loading, with frequencies up to approximately 100 Hz into
      analytical plasmas. In this technical note, the analytical figures of merit of
      laser-induced breakdown spectroscopy and inductively coupled plasma-optical
      emission spectrometry with single droplet introduction are reported using Ca and
      Au standard solutions as examples. Future engineering is required to reduce the
      total sample volumes from the relatively large sample reservoir of the current
      study, thereby reducing potential issues of washout while enabling analysis of
      ultralow total sample volumes.

PMID- 20151661
TI  - Monolithic superhydrophobic polymer layer with photopatterned virtual channel for
      the separation of peptides using two-dimensional thin layer chromatography
      desorption electrospray ionization mass spectrometry.
AB  - Superhydrophobic monolithic porous polymer layers with a photopatterned
      hydrophilic channel have been prepared. These layers were used for two
      dimensional thin layer chromatography of peptides. The 50 microm thin poly(butyl
      methacrylate-co-ethylene dimethacrylate) layers supported onto 4.0 x 3.3 cm glass
      plates were prepared using UV-initiated polymerization in a simple glass mold.
      Photografting of a mixture of 2-acrylamido-2-methyl-1-propanesulfonic acid and 2
      hydroxyethyl methacrylate carried out through a mask afforded a 600 microm wide
      virtual channel along one side of the layer. This channel, which contains
      ionizable functionalities, enabled the first dimension separation in ion exchange
      mode. The aqueous mobile phase migrates only through the channel due to the large
      difference in surface tension at the interface of the hydrophilic channel and the
      superhydrophobic monolith. The unmodified part of the layer featuring hydrophobic
      chemistry was then used for the reversed phase separation in the orthogonal
      second dimension. Practical application of our technique was demonstrated with a
      rapid 2D separation of a mixture of model peptides differing in hydrophobicity
      and isoelectric point using a combination of ion-exchange and reversed phase
      modes. In the former mode, the peptides migrated 11 mm in less than 1 min.
      Detection of fluorescently labeled peptides was achieved through UV light
      visualization. Separation of the native peptides was monitored directly using a
      desorption electrospray ionization (DESI) source coupled to a mass spectrometer.
      Unidirectional surface scanning with the DESI source was found suitable to
      determine both the location of each separated peptide and its molecular mass.

PMID- 20151664
TI  - Second-order state-specific multireference Moller-Plesset perturbation theory (SS
      MRMPPT) applied to geometry optimization.
AB  - The performance of a numerically oriented gradient scheme for the previously
      introduced second-order state-specific multireference Moller-Plesset perturbation
      theory (SS-MRMPPT) has been tested to compute certain geometrical parameters
      (such as bond lengths and angles). Various examples [H2O, O3, N2H2, C2H4, C2H2F2,
      1,3-butadiene (C4H6), cyclobutadiene (C4H4), and 2,6-pyridynium cation
      (C5NH4(+))] have been presented to validate the implementation of the SS-MRMPPT
      gradient approach. To illustrate the reliability of our findings, comparisons
      have been made with the previously reported theoretical results. The accuracy of
      our calculations has further been assessed by comparing with the experimental
      results whenever available. On the basis of the present work, we arrive at the
      conclusion that the SS-MRMPPT gradient scheme has substantial potential in
      computing the geometrical parameters for several rather diverse molecular
      systems, whether charged or neutral and having the closed-shell ground state or
      being open-shell radicals or biradicals or strongly perturbed by intruders. It is
      worthwhile to emphasize that the present work represents the first systematic
      application of the SS-MRMPPT numerical gradient approach.

PMID- 20151663
TI  - Integrated device for online sample buffer exchange, protein enrichment, and
      digestion.
AB  - An integrated sample treatment device, composed of a membrane interface and a
      monolithic hybrid silica based immobilized enzymatic reactor (IMER), was
      developed for the simultaneous sample buffer exchange, protein enrichment, and
      online digestion, by which for the sample buffer, the acetonitrile content was
      reduced to approximately 1/10 of the initial one, and the pH value was adjusted
      from approximately 3.0 to approximately 8.0, compatible for online trypsin
      digestion. Furthermore, the signal intensity of myoglobin digests was improved by
      over 10 times. Such an integrated device was successfully applied to the online
      treatment of three protein eluates obtained by reverse-phase liquid
      chromatography (RPLC) separation, followed by further protein digest analysis
      with microreverse-phase liquid chromatography-electrospray ionization-tandem mass
      spectrometry (microRPLC-ESI-MS/MS). The experimental results showed that the
      performance of such an integrated sample treatment device was comparable to that
      of the traditional offline sample treatment method, including lyophilization and
      in-solution digestion. However, the consumed time was reduced to 1/192. All these
      results demonstrate that such an integrated sample treatment device could be
      further online coupled with protein separation, peptide separation, and
      identification, to achieve high-throughput proteome analysis.

PMID- 20151665
TI  - Exploring electron spin-spin interactions of paramagnetic iron and radical
      cations of bacteriochlorophyll from oxidized LH1 in the presence of electron
      transfer in the frozen state.
AB  - Cation free radicals of bacteriochlorophyll (BChl(+)) are formed in the light
      harvesting complex 1 (LH1) of photosynthetic bacteria upon oxidation by potassium
      ferricyanide. Unusually narrow EPR line widths are observed for BChl(+) in the
      frozen state. These narrow line widths are consistent with a molecular-wire
      behavior where rapid electron/hole transfer occurs between the BChl constituents
      of the pigment array responsible for light harvesting in bacterial
      photosynthesis. However, in addition to electron/hole transfer, two distinct
      types of spin-spin exchange could contribute the EPR line width narrowing, thus
      obfuscating the determination of LH1 as a molecular wire. First, because excess
      ferricyanide ion is always present during the EPR measurements, electron spin
      spin interactions between the paramagnetic ferricyanide and BChl(+) could be a
      major source of the EPR line width changes previously attributed solely to
      electron/hole hopping within the array of BChl molecules in a LH1 unit. Fixing
      the potential of the ferricyanide/ferrocyanide redox couple gives a constant
      concentration of paramagnetic iron as the amount of BChl oxidized in LH1 changes.
      As long as the fraction of oxidized BChl in LH1 remains the same, the EPR line
      width is found independent of the concentration of the ferricyanide oxidant.
      Additionally, the trend in EPR line width as a function of temperatures depends
      only on the fraction of oxidized BChl and not on the concentration of
      ferricyanide ion. Second, spin-spin exchange interactions between BChl(+)s within
      LH1 rings could also change the EPR line width. Using LH1 preparations containing
      at most a few BChl cations per LH1 complex also eliminates the occurrence of
      significant electron spin-spin exchange as a cause of the observed line width
      narrowing in minimally oxidized LH1. This investigation of the two types of
      electron spin-spin exchange interactions demonstrates (1) that electron/hole
      hopping can take place in oxidized LH1 without involvement of paramagnetic
      ferricyanide or spin-spin exchange between BChl(+)s and (2) that LH1 maintains a
      molecular-wire nature at cryogenic temperatures.

PMID- 20151666
TI  - Resins with "nano-raisins".
AB  - Thermosensitive hydrogels are materials which globally shrink/swell in water when
      the surrounding temperature crosses the lower critical solution temperature
      (LCST). We demonstrate here a novel class of cross-linked polymeric materials,
      which do not shrink/swell in water globally, but nevertheless reveal a hydrogel
      like, stimuli-responsive behavior. In particular, they demonstate a positive
      thermosensitive release of the embedded fluorescent dye significantly modulated
      when temperature crosses the LCST. Using staining with copper, transmission
      electron microscopy and energy dispersive X-ray analysis, we show that this
      effect is associated with nanogel "raisins" dispersed in such materials (e.g.,
      polymer nanofibers). Shrinkage of individual nanogel "raisins" at elevated
      temperatures increases nanoporosity via increased exposure of the existing
      nanopores to water, or formation of new nanopores/nanocracks in the overstretched
      polymer matrix in the vicinity of shrinking nanogel "raisins". As a result, the
      release rate of the embedded dye from the nanofibers increases at elevated
      temperatures. We suggest that similar functional materials with embedded nanogel
      "raisins" will find applications in nanofluidics and as drug carriers for
      controlled drug release.

PMID- 20151667
TI  - Dynamic behavior of the water droplet impact on a textured
      hydrophobic/superhydrophobic surface: the effect of the remaining liquid film
      arising on the pillars' tops on the contact time.
AB  - We have fabricated a series of textured silicon surfaces decorated by square
      arrays of pillars whose radius and pitch can be adjusted independently. These
      surfaces possessed a hydrophobic/superhydrophobic property after silanization.
      The dynamic behavior of water droplets impacting these structured surfaces was
      examined using a high-speed camera. Experimental results validated that the
      remaining liquid film on the pillars' tops gave rise to a wet surface instead of
      a dry surface as the water droplet began to recede away from the textured
      surfaces. Also, experimental results demonstrated that the difference in the
      contact time was subjected to the solid fraction referred to as the ratio of the
      actual area contacting with the liquid to its projected area on the textured
      surface. Because the mechanism by which the residual liquid film emerges on the
      pillars' tops can essentially be ascribed to the pinch-off of the liquid threads,
      we further addressed the changes in the contact time in terms of the
      characteristic time of pinch-off of an imaginary liquid cylinder whose radius is
      related to the solid fraction and the maximum contact area. The match of the
      theoretical analysis and the experimental results substantiates the assumption
      aforementioned.

PMID- 20151669
TI  - Temperature-responsive properties and drug solubilization capacity of amphiphilic
      copolymers based on N-vinylpyrrolidone and vinyl propyl ether.
AB  - A series of amphiphilic copolymers were synthesized by free-radical
      copolymerization of N-vinylpyrrolidone (NVP) with vinyl propyl ether (VPE), and
      the structure of the copolymers was characterized by elemental analysis and gel
      permeation chromatography. The reactivity of VPE in copolymerization was found to
      be significantly lower than the reactivity of NVP, which resulted in a decrease
      of copolymers' yields and molecular weights with higher content of VPE in the
      feed mixture. An investigation of the behavior of the copolymers in aqueous
      solutions at different temperatures by dynamic light scattering revealed the
      presence of lower critical solution temperature, which depending on the content
      of VPE ranged within 23-38 degrees C. Aqueous solutions of these copolymers were
      studied by fluorescent spectroscopy with pyrene as a polarity probe to reveal the
      formation of hydrophobic domains. The copolymers were found to be useful for
      enhancing the solubility of riboflavin in water.

PMID- 20151670
TI  - Novel irreversible epidermal growth factor receptor inhibitors by chemical
      modulation of the cysteine-trap portion.
AB  - Irreversible EGFR inhibitors can circumvent acquired resistance to first
      generation reversible, ATP-competitive inhibitors in the treatment of non-small
      cell lung cancer. They contain both a driver group, which assures target
      recognition, and a warhead, generally an acrylamide or propargylamide fragment
      that binds covalently to Cys797 within the kinase domain of EGFR. We performed a
      systematic exploration of the role for the warhead group, introducing different
      cysteine-trapping fragments at position 6 of a traditional 4-anilinoquinazoline
      scaffold. We found that different reactive groups, including epoxyamides
      (compounds 3-6) and phenoxyacetamides (compounds 7-9), were able to irreversibly
      inhibit EGFR. In particular, at significant lower concentrations than gefitinib
      (1), (2R,3R)-N-(4-(3-bromoanilino)quinazolin-6-yl)-3-(piperidin-1
      ylmethyl)oxirane-2-carboxamide (6) inhibited EGFR autophosphorylation and
      downstream signaling pathways, suppressed proliferation, and induced apoptosis in
      gefitinib-resistant NSCLC H1975 cells, harboring the T790M mutation in EGFR.

PMID- 20151672
TI  - Vapor stabilizing substrates for superhydrophobicity and superslip.
AB  - The success of rough substrates designed for superhydrophobicity and superslip
      relies crucially on the presence of air pockets in the roughness grooves. This
      air is supplied by the surrounding environment. However, if the rough substrates
      are used in enclosed configurations, such as in fluidic networks, the air pockets
      may not be sustained in the roughness grooves and may diffuse out. In this work,
      a design approach based on sustaining a vapor phase of the liquid in the
      roughness grooves, instead of relying on the presence of air, is explored. The
      resulting surfaces, referred to as vapor stabilizing substrates, are deemed to be
      more robust against wetting transition even if no air is present.

PMID- 20151673
TI  - Protein-based aqueous-multiphasic systems.
AB  - This paper reports the formation of aqueous-multiphasic systems (AMPS)
      exclusively made using elastin-like polypeptides (ELP) which have the ability to
      undergo reversible inverse phase transitions. Manipulating variables such as the
      salt concentration and the molecular weight and the composition of ELPs (using
      different amino acid sequences or by fusing the ELP with different functional
      proteins) permits modulation of the temperature at which phase transition takes
      place, the number of phases that are formed, and the composition of the multiple
      aqueous phases. Using these variables, isotropic hybrid colloids with tunable
      functionality (in this case, fluorescent intensity) and anisotropic colloids with
      variable morphologies could be generated. While formation of AMPS and anisotropic
      colloids has been reported in the literature using synthetic polymers, to our
      knowledge this is the first report of generating such systems using proteins.

PMID- 20151671
TI  - Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor
      A (VEGF-A) interaction.
AB  - We report the molecular design and synthesis of EG00229, 2, the first small
      molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural
      characterization of NRP1-ligand complexes by NMR spectroscopy and X-ray
      crystallography. Mutagenesis studies localized VEGF-A binding in the NRP1 b1
      domain and a peptide fragment of VEGF-A was shown to bind at the same site by
      NMR, providing the basis for small molecule design. Compound 2 demonstrated
      inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in
      endothelial cells. Inhibition of migration of endothelial cells was also
      observed. The viability of A549 lung carcinoma cells was reduced by 2, and it
      increased the potency of the cytotoxic agents paclitaxel and 5-fluorouracil when
      given in combination. These studies provide the basis for design of specific
      small molecule inhibitors of ligand binding to NRP1.

PMID- 20151674
TI  - Size matters: influence of the size of nanoparticles on their interactions with
      ligands immobilized on the solid surface.
AB  - The correlation between the size of biotinylated nanoparticles and their affinity
      in relation to interactions with the solid surface was investigated. The silica
      particles with a diameter of 50-200 nm containing amino groups on the surface
      were labeled with different quantities of biotin. The affinity properties of
      biotinylated nanoparticles were studied using a Biacore 3000 instrument equipped
      with a streptavidin-coated sensor chip (SA chip). It was shown that the increase
      in the particle size from 50 to 200 nm reduced the affinity (K(D)) of biotin
      streptavidin interactions from 1.2 x 10(-12) to 1.2 x 10(-10) M. It was found
      that the particles with higher concentrations of immobilized biotin on particle
      surfaces demonstrated stronger binding with streptavidin.

PMID- 20151676
TI  - Nanoscale patterning of microtextured surfaces to control superhydrophobic
      robustness.
AB  - Most naturally existing superhydrophobic surfaces have a dual roughness structure
      where the entire microtextured area is covered with nanoscale roughness. Despite
      numerous studies aiming to mimic the biological surfaces, there is a lack of
      understanding of the role of the nanostructure covering the entire surface. Here
      we measure and compare the nonwetting behavior of microscopically rough surfaces
      by changing the coverage of nanoroughness imposed on them. We test the surfaces
      covered with micropillars, with nanopillars, with partially dual roughness (where
      micropillar tops are decorated with nanopillars), and with entirely dual
      roughness and a real lotus leaf surface. It is found that the superhydrophobic
      robustness of the surface with entirely dual roughness, with respect to the
      increased liquid pressure caused by the drop evaporation and with respect to the
      sagging of the liquid meniscus due to increased micropillar spacing, is greatly
      enhanced compared to that of other surfaces. This is attributed to the
      nanoroughness on the pillar bases that keeps the bottom surface highly water
      repellent. In particular, when a drop sits on the entirely dual surface with a
      very low micropillar density, the dramatic loss of hydrophobicity is prevented
      because a novel wetting state is achieved where the drop wets the micropillars
      while supported by the tips of the basal nanopillars.

PMID- 20151675
TI  - N-Heterocyclic carbene catalyzed asymmetric hydration: direct synthesis of alpha
      protio and alpha-deuterio alpha-chloro and alpha-fluoro carboxylic acids.
AB  - Asymmetric hydration of alpha,alpha-dichloro aldehydes and alpha-halo enals via a
      NHC-catalyzed redox process to yield enantioenriched alpha-chloro and alpha
      fluoro carboxylic acids is described herein. The developed reaction allows for
      installation of an alpha-deuterium to give rise to enantioenriched alpha-deutero
      alpha-halo acids using D(2)O as the deuteron source.

PMID- 20151677
TI  - Discovery of 4-amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides
      as selective, orally active inhibitors of protein kinase B (Akt).
AB  - Protein kinase B (PKB or Akt) is an important component of intracellular
      signaling pathways regulating growth and survival. Signaling through PKB is
      frequently deregulated in cancer, and inhibitors of PKB therefore have potential
      as antitumor agents. The optimization of lipophilic substitution within a series
      of 4-benzyl-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amines provided ATP
      competitive, nanomolar inhibitors with up to 150-fold selectivity for inhibition
      of PKB over the closely related kinase PKA. Although active in cellular assays,
      compounds containing 4-amino-4-benzylpiperidines underwent metabolism in vivo,
      leading to rapid clearance and low oral bioavailability. Variation of the linker
      group between the piperidine and the lipophilic substituent identified 4-amino-1
      (7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides as potent and orally
      bioavailable inhibitors of PKB. Representative compounds modulated biomarkers of
      signaling through PKB in vivo and strongly inhibited the growth of human tumor
      xenografts in nude mice at well-tolerated doses.

PMID- 20151678
TI  - Iridoids and lignans from Valeriana jatamansi.
AB  - Thirteen new iridoids including seven iridolactones, jatamanins A-M (1-13), and a
      new lignan, (+)-9'-isovaleroxylariciresinol (14), together with seven known
      iridoids and 13 lignans were obtained from whole plants of Valeriana jatamansi.
      Structures of the new compounds were determined by spectroscopic and
      crystallographic methods, and the absolute configuration of compound 1 was
      assigned by application of the modified Mosher method. Jatamanins H (8) and I (9)
      are iridolactones with an unusual C-8-C-11 oxygen bridge, forming a cage-like
      structure. (+)-9'-Isovaleroxylariciresinol (14) showed significant in vitro
      cytotoxicity against PC-3M and HCT-8 cell lines, with IC(50) values of 8.1 and
      5.3 microM, respectively.

PMID- 20151679
TI  - Angiotensin I-converting enzyme inhibitory peptides generated from in vitro
      gastrointestinal digestion of pork meat.
AB  - The main purpose of this work was to study the generation of Angiotensin I
      converting enzyme inhibitory (ACEI) peptides after gastrointestinal digestion of
      pork meat by the action of pepsin and pancreatin at simulated gut conditions. The
      hydrolysate was further subjected to reverse phase chromatography in order to
      separate the fractions with ACEI activity. Using MALDI-TOF/TOF mass spectrometry,
      12 peptides were identified in these fractions. It is worth highlighting the
      novel peptides ER, KLP, and RPR with IC(50) values of 667 microM, 500 microM, and
      382 microM, respectively. Results obtained by MALDI-TOF/TOF mass spectrometry
      were complemented by a second approach consisting of the analysis of the
      hydrolysate directly by nanoLC-ESI-MS/MS followed by a study of the obtained
      sequences and comparison with known ACEI peptide sequences. By using these two
      approaches, a total of 22 peptides were selected for its synthesis and further in
      vitro assay of ACEI activity. The strongest ACE inhibition was observed for
      peptide KAPVA (IC(50) = 46.56 microM) followed by the sequence PTPVP (IC(50) =
      256.41 microM). Sequence similarity searches revealed that these two peptides
      derive from muscle titin, constituting the first identified ACEI peptides coming
      from this protein. This is also the first time that ACEI sequences MYPGIA and
      VIPEL have been reported. Other identified and synthesized sequences showed less
      ACEI activity. The obtained results evidence the potential of pork meat proteins
      as a source of antihypertensive peptides after gastrointestinal digestion.

PMID- 20151680
TI  - Ac dielectrophoresis of tin oxide nanobelts suspended in ethanol: manipulation
      and visualization.
AB  - This article presents results of detailed and direct real-time observations of
      the wide variety of SnO(2) nanobelt motions induced by ac dielectrophoresis (DEP)
      in an innovative microfluidic setup. High ac electric fields were generated on a
      gold microelectrode (approximately 20 microm electrode gap) array, patterned on a
      glass substrate and covered by a approximately 10 microm tall
      polydimethylsiloxane (PDMS) microchannel. Ethanol suspended SnO(2) nanobelts were
      introduced into the microchannel, and the DEP experiments were performed.
      Negative DEP (repulsion) of the nanobelts was observed in the low-frequency range
      (<100 kHz) of the applied electric field, which caused rigid body motion as well
      as deformation of the nanobelts. The negative DEP effect observed in ethanol is
      unusual and contrary to what is predicted by the Clausius-Mossotti factor (using
      bulk SnO(2) conductivity and permittivity values) of the dipole approximation
      theory. In the high-frequency range (approximately 1-10 MHz), positive DEP
      (attraction) of the nanobelts was observed. Pearl chain formation involving short
      nanobelts and particles was also observed in the two DEP regimes.

PMID- 20151681
TI  - Multiplexed real-time polymerase chain reaction on a digital microfluidic
      platform.
AB  - This paper details the development of a digital microfluidic platform for
      multiplexed real-time polymerase chain reactions (PCR). Liquid samples in
      discrete droplet format are programmably manipulated upon an electrode array by
      the use of electrowetting. Rapid PCR thermocycling is performed in a closed-loop
      flow-through format where for each cycle the reaction droplets are cyclically
      transported between different temperature zones within an oil-filled cartridge.
      The cartridge is fabricated using low-cost printed-circuit-board technology and
      is intended to be a single-use disposable device. The PCR system exhibited
      remarkable amplification efficiency of 94.7%. To test its potential application
      in infectious diseases, this novel PCR system reliably detected diagnostic DNA
      levels of methicillin-resistant Staphylococcus aureus (MRSA), Mycoplasma
      pneumoniae , and Candida albicans . Amplification of genomic DNA samples was
      consistently repeatable across multiple PCR loops both within and between
      cartridges. In addition, simultaneous real-time PCR amplification of both
      multiple different samples and multiple different targets on a single cartridge
      was demonstrated. A novel method of PCR speed optimization using variable cycle
      times has also been proposed and proven feasible. The versatile system includes
      magnetic bead handling capability, which was applied to the analysis of simulated
      clinical samples that were prepared from whole blood using a magnetic bead
      capture protocol. Other salient features of this versatile digital microfluidic
      PCR system are also discussed, including the configurability and scalability of
      microfluidic operations, instrument portability, and substrate-level integration
      with other pre- and post-PCR processes.

PMID- 20151682
TI  - Multichannel capillary electrophoresis microdevice and instrumentation for in
      situ planetary analysis of organic molecules and biomarkers.
AB  - The Multichannel Mars Organic Analyzer (McMOA), a portable instrument for the
      sensitive microchip capillary electrophoresis (CE) analysis of organic compounds
      such as amino acid biomarkers and polycyclic aromatic hydrocarbons (PAHs), is
      developed. The instrument uses a four-layer microchip, containing eight CE
      analysis systems integrated with a microfluidic network for autonomous fluidic
      processing. The McMOA has improved optical components that integrate 405 nm laser
      excitation with a linear-scanning optical system capable of multichannel real
      time fluorescence spectroscopic analysis. The instrumental limit of detection is
      6 pM (glycine). Microfluidic programs are executed to perform the automated
      sequential analysis of an amine-containing sample in each channel as well as
      eight consecutive analyses of alternating samples on the same channel,
      demonstrating less than 1% cross-contamination. The McMOA is used to identify the
      unique fluorescence spectra of nine components in a PAH standard and then applied
      to the analysis of a sediment sample from Lake Erie. The presence of
      benzo[a]pyrene and perylene in this sample is confirmed, and a peak coeluting
      with anthanthrene is disqualified based on spectral analysis. The McMOA exploits
      lab-on-a-chip technologies to fully integrate complex autonomous operations
      demonstrating the facile engineering of microchip-CE platforms for the analysis
      of a wide variety of organic compounds in planetary exploration.

PMID- 20151684
TI  - The theoretical quest for sulfate of Ag(2+): genuine Ag(II)SO4, diamagnetic
      Ag(I)2S2O8, or rather mixed-valence Ag(I)[Ag(III)(SO4)2]?
AB  - In an attempt to extend the chemistry of Ag(II) compounds to novel ligand
      environments, we have examined various polymorphs of an as yet unknown compound
      of AgSO(4) stoichiometry by means of a quantum chemistry DFT approach. Since
      AgSO(4) has not yet been prepared, we were interested whether genuine divalent
      silver, Ag(II), could be stabilized in the presence of sulfate (SO(4)(2-)) anions
      or whether it would rather have a tendency toward disproportionation to
      Ag(I)/Ag(III) (as known from binary oxide, "AgO") or maybe toward the formation
      of peroxodisulfate (S(2)O(8)(2-)) of Ag(I). Considering all important
      electromeric forms, Ag(II)SO(4), Ag(I)Ag(III)(SO(4))(2), and Ag(I)(2)S(2)O(8), in
      a variety of crystal structures, we examined their dynamical (vibrational)
      stability and discussed the most stable phases from the point of view of
      structural features thought to be crucial for appearance of high-T(C)
      superconductivity. We show that a compound of a nominal stoichiometry, AgSO(4),
      should most likely be a genuine paramagnetic sulfate of divalent silver which
      forms 3D ...Ag-O-S(O(2))-O... networks, and--unlike CuSO(4)--shows no direct
      connections of paramagnetic Ag(II) centers via Ag-O bridges. This must lead to
      low electronic dimensionality and concomitant low potential for the appearance of
      high-T(C) superconductivity. Finally, we discuss structural features of the most
      stable phase of AgSO(4) predicted here in a broader context of crystal structures
      of group 11 metals.

PMID- 20151683
TI  - Ultrasensitive quantification of serum vitamin D metabolites using selective
      solid-phase extraction coupled to microflow liquid chromatography and isotope
      dilution mass spectrometry.
AB  - The capacity for quantification of active metabolites of vitamin D (VitD) is
      highly valuable to evaluate the risks and therapies for numerous diseases such as
      multiple sclerosis. However, the extremely low circulating levels and poor
      detectability of some dihydroxyl metabolites such as the 1alpha,25-dihydroxy
      VitD(3) constitute a daunting challenge. Based on the combination of a selective
      solid-phase extraction (SPE) and a microflow liquid chromatography tandem mass
      spectrometry (microLC-MS/MS), we developed an ultrasensitive method for the
      robust, selective, and accurate quantification of four key VitD metabolites,
      including 25-hydroxy-VitD(2), 25-hydroxy-VitD(3), 24(R),25-dihydroxy-VitD(3), and
      1alpha,25-dihydroxy-VitD(3), in serum samples. A one-step derivatization was
      employed to improve the ionization efficiency of the metabolites. The SPE
      procedure was optimized so that the analytes were selectively extracted from
      serum, while the sample matrix was substantially simplified. By eliminating
      majority of undesirable compounds from the matrix, the selective SPE enabled a
      high sample loading volume on the microLC column without causing overcapacity of
      the microLC column and thus helped to achieve ultralow detect limits in serum. An
      on-column sample focusing approach was employed to prevent band-broadening, and a
      sufficient microLC separation was achieved to eliminate endogenous interferences
      and to minimize ion suppression effect. Detect limits of the four metabolites
      ranged from 0.5-1 pg/mL, and the linearity was excellent for all compounds. The
      method showed high quantitative accuracy (error < 13.8%) and precision (CV <
      14.1%). For 1alpha,25-dihydroxy-VitD(3), a lower limit of quantification (LLOQ)
      of 5 pg/mL was validated. This high level of sensitivity, for the first time,
      enabled the robust and consistent LC/MS/MS-based analysis of the four metabolites
      in a large-scale clinical investigation. Serum samples from 281 multiple
      sclerosis patients and 22 healthy subjects were analyzed, and it was discovered
      that the levels of both 24(R),25-dihydroxy-VitD(3) and 1alpha,25-dihydroxy
      VitD(3) were significantly lower in patients than healthy subjects (P < 0.05).
      This novel observation may imply that the incidence of multiple sclerosis is
      inversely associated with the levels of the two metabolites. Moreover, the method
      was highly robust and reproducible as evaluated extensively in the clinical
      analysis; therefore, it could serve as a more selective and accurate alternative
      to immunoassay for large-scale clinical studies.

PMID- 20151685
TI  - One- and two-electron-transfer reactions of (dpp-Bian)Sm(dme)3.
AB  - The reduction of 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-Bian)
      with an excess of samarium in 1,2-dimethoxyethane (dme) affords the Sm(II)
      complex (dpp-Bian)Sm(dme)(3) (1). The reaction of 1 with 0.5 mol equiv of 1,2
      dibromostilbene proceeds with the formation of the dimeric Sm(III) complex [(dpp
      Bian)SmBr(dme)](2) (2). Oxidation of both the metal and the dpp-Bian ligand takes
      place if 1 is reacted with equimolar amounts of 1,2-dibromostilbene or iodine,
      yielding the monomeric Sm(III) derivatives (dpp-Bian)SmBr(2)(dme) (3) and (dpp
      Bian)SmI(2)(THF)(2) (4; THF = tetrahydrofuran), respectively. The reaction of 1
      with 0.5 mol equiv of iodine followed by 0.5 mol equiv of tetramethylthiuram
      disulfide gives the Sm(III) complex (dpp-Bian)SmI[SC(S)NMe(2)](dme) (5). Compound
      4 and tBuOK react with the formation of the iodine-bridged dimer [(dpp
      Bian)SmI(OtBu)(THF)](2) (6). Complexes 1 and 2 have been characterized by (1)H
      NMR spectroscopy and complexes 2-6 by their molecular structures, which were
      determined by single-crystal X-ray diffraction.

PMID- 20151686
TI  - Large changes in electronic structures of Ru2(6+) species caused by the
      variations of the bite angle of guanidinate ligands: tuning magnetic behavior.
AB  - Syntheses and characterization of two Ru(2)(6+) paddlewheel compounds having very
      different magnetic behavior are reported. The compounds Ru(2)(tbn)(4)Cl(2), 1,
      and Ru(2)(tbo)(4)Cl(2), 2 (where tbn = the anion of 1,5,7-triazabicyclo[4.3.0]non
      6-ene and tbo = the anion of 1,4,6-triazabicyclo[3.3.0]oct-4-ene), have four
      equatorial bicyclic guanidinate ligands and two chloride ions in axial positions.
      They show large disparity in Ru-Ru distances of about 0.11 A (2.389(3) and
      2.499(3) A at 30 K for 1 and 2, respectively) that is attributed to the
      divergence in the bite angle of the ligand. Variable temperature structural data
      show no significant changes in the Ru-Ru distances between 30 and 213 K
      suggesting that the electronic structure remains unchanged in this temperature
      range for both compounds. Magnetic studies of 1 indicate there are two unpaired
      electrons at room temperature but the compound behaves as essentially diamagnetic
      at approximately 2 K. Compound 2 is non-magnetic across all temperatures in the
      range of 2 to 300 K. Density functional theory calculations suggest a
      pi(4)pi*(4)delta(2) electronic configuration for 2, while the magnetic behavior
      and structural data for 1 are consistent with a sigma(2)pi(4)delta(2)pi*(2)
      electronic configuration. This shows the importance of the ligand bite angle in
      determining the electronic configuration of the diruthenium unit and a way to
      tune magnetic behavior.

PMID- 20151687
TI  - Synthesis, magnetic structure, and properties of a layered cobalt-hydroxide
      ferromagnet, Co5(OH)6(SeO4)2(H2O)4.
AB  - The synthesis and nuclear and magnetic structures from the powder diffraction of
      Co(II)(5)(OH)(6)(SeO(4))(2)(H(2)O)(4) and its deuterated analogues as well as
      their infrared spectral, thermal, and magnetic properties are reported. The
      nuclear structure consists of brucite-like cobalt hydroxide layers connected by
      ...OSeO(3)-Co(H(2)O)(4)-O(3)SeO... bridges. The two independent cobalt atoms
      within the layer are arranged in chains along the b axis creating an anisotropy
      within each layer. The interlayer distance (10.718 A) is the only parameter to
      increase compared to the sulfate analogue (10.273 A). The infrared spectra and
      thermal properties are similar to those reported for the sulfate analogue. Due to
      the ferromagnetic exchange between the nearest-neighbor cobalt atoms within the
      layer, satisfying the Goodenough-Kanamori rule, and the weak interlayer exchange,
      an overall ferromagnet is obtained. The ferromagnetic order at 9 K was confirmed
      by the ac susceptibilities, the saturation magnetization, and most importantly
      the enhancement of some Bragg diffraction peaks below the Curie temperature. The
      moments of all the cobalt atoms were found to be aligned along the b axis with a
      moment of 3.25(8) mu(B) each giving the best fit. The increase in layer distance
      and the electron density by replacing sulfur by selenium lowers the Curie
      temperature.

PMID- 20151689
TI  - Antimitogenic polymer drugs based on AMPS: monomer distribution-bioactivity
      relationship of water-soluble macromolecules.
AB  - A number of polysulfonated molecules have demonstrated their interaction with
      fibroblast growth factor (FGF), hampering their binding to its receptors (low
      affinity heparan sulfate proteoglycans (HSPG) and high affinity tyrosine kinase
      FGF receptors) and inhibiting the intracellular signaling and mitogenic response
      in cultured endothelial cells. The aim of this work was the synthesis and
      characterization of new copolymers based on 2-acrylamido-2-methylpropane sulfonic
      acid (AMPS) with antiproliferative activity for antitumoral applications. N
      Vinylpyrrolidone (VP) or butyl acrylate (BA) was copolymerized with the
      sulfonated monomer to obtain macromolecules with different
      hydrophilic/hydrophobic balance and distribution of the sulfonated groups within
      the macromolecules. In vitro cell culture proliferative assays showed that
      monomer distribution affected the inhibition of the proliferative action of FGF.
      Reactivity ratios of the systems were determined following the free radical
      copolymerization by in situ (1)H NMR, and the correlation of the monomer sequence
      distribution with the bioactivity is discussed.

PMID- 20151688
TI  - Chemistry of vanadaboranes: synthesis, structures, and characterization of
      organovanadium sulfide clusters with disulfido linkage.
AB  - Vanadaborane, [(CpV)(2)(B(2)H(6))(2)] (Cp = eta(5)-C(5)H(5)), 1 reacts with
      elemental sulfur to afford the hexasulfide cluster [(CpV)(2)S(4)(mu-eta(1)
      S(2))], 2 in high yield. Compound 2 is a notable example of an organovanadium
      sulfide cluster in which the [V(2)S(4)] atoms define a bicapped tetrahedron
      framework, with one mu-eta(1)-S(2) ligand bridged the two (CpV) moieties. The
      sulfur atom in [V(2)S(4)] core in 2 is a four-skeletal-electron donor
      isoelectronic with the BH(3) unit; therefore, the replacement of boron hydride in
      1 by four sulfur atoms necessitates the formation of a bicapped tetrahedron
      [V(2)S(4)] framework. Furthermore, this is the only reported example of a
      bimetallic hexasulfide cluster containing vanadium. Pyrolysis of 1 with bis
      chalcogenide ligands such as Ph(2)S(2) and Bz(2)Se(2) (Bz = PhCH(2)), results in
      the formation of substituted vanadahexaboranes [(CpV)(2)B(4)H(12-x)L(x)], 3-5 (3:
      L = SPh: x = 3; 4: L = SPh, x = 2; 5: L = SeBz: x = 1) in modest yield. All these
      new compounds have been characterized by mass, (1)H, (11)B, (13)C NMR
      spectroscopy, and elemental analysis, and the structural types were unequivocally
      established by crystallographic analysis of compounds 2-5.

PMID- 20151690
TI  - (HCN)(m)-M(n) (M = K, Ca, Sr): vibrational excitation induced solvation and
      desolvation of dopants in and on helium nanodroplets.
AB  - Infrared (IR) laser spectroscopy is used to probe the rotational and vibrational
      dynamics of the (HCN)(m)-M(n) (M = K, Ca, Sr) complexes, either solvated within
      or bound to the surface of helium nanodroplets. The IR spectra of the (HCN)(m)-K
      (m = 1-3), HCN-Sr, and HCN-Ca complexes have the signature of a surface species,
      similar to the previously reported spectra of HCN-M (M = Na, K, Rb, Cs)
      [Douberly, G. E.; Miller, R. E. J. Phys. Chem. A 2007, 111, 7292.]. A second band
      in the HCN-Ca spectrum is assigned to a solvated complex. The relative
      intensities of the two HCN-Ca bands are droplet size dependent, with the solvated
      species being favored in larger droplets. IR-IR double resonance spectroscopy is
      used to probe the interconversion of the two distinct HCN-Ca populations. While
      only a surface-bound HCN-Sr species is initially produced, CH stretch vibrational
      excitation results in a population transfer to a solvated state. Complexes
      containing multiple HCN molecules and one Sr atom are surface-bound, while the
      nu(1) (HCN)(2)Ca spectrum has both the solvated and surface-bound signatures. All
      HCN-(Ca,Sr)(n) (n > or = 2) complexes are solvated following cluster formation in
      the droplet. Density-functional calculations of helium nanodroplets interacting
      with the HCN-M show surface binding for M = Na with a binding energy of 95 cm(
      1). The calculations predict a fully solvated complex for M = Ca. For M = Sr, a
      2.2 cm(-1) barrier is predicted between nearly isoenergetic surface binding and
      solvated states.

PMID- 20151691
TI  - Cyclooctatetraenes tetrakis-annelated with alpha-dithio- or alpha
      diselenocarbonyl groups: diradicals predicted to have ground states with 10 pi
      electrons in the eight-membered ring and two-center, three-electron, sigma bonds
      between two pairs of chalcogen atoms.
AB  - (U)B3LYP calculations with the 6-31+G(d) and 6-311+G(2df) basis sets have been
      carried out on cyclooctatetraenes 6 and 7, in which the COT ring is tetrakis
      annelated with alpha-dithio- or alpha-diselenocarbonyl groups. Transferring two
      electrons from the high-lying b(1g) and e(u) sigma MOs in 6 and 7 into the
      unoccupied, nonbonding, COT pi orbital is computed to be energetically favorable.
      The lowest D(4h) electronic state is calculated to be (3)E(u), which formally
      contains 10 pi electrons in the eight-membered ring and has two unpaired
      electrons in sigma MOs. The (3)E(u) state undergoes a first-order Jahn-Teller
      distortion to form 6d and 7d, in which the pair of one-electron holes in the
      sigma MOs is stabilized by the formation of two, two-center, three-electron bonds
      between pairs of chalcogen atoms that are diagonally across the eight-membered
      ring from each other. The corresponding open-shell singlets are computed to be
      about 1 kcal/mol lower in energy than the Jahn-Teller distorted triplets.
      Molecules 6i and 7i, in which the C-C bond in one four-membered ring is cleaved,
      are computed to be lower in energy than 6d and 7d. However, a substantial barrier
      is predicted to separate each of the two pairs of isomers so that 6d and 7d
      should, at least in principle, be isolable.

PMID- 20151692
TI  - Attempted isolation and characterization of diazirinone (N2CO).
AB  - Stimulated and intrigued by the report of the synthesis of diazirinone (1), a
      metastable adduct of N(2) and CO, we carried out further experimental and
      theoretical studies aimed at the detailed spectroscopic characterization of this
      species. Our attempts to generate and detect diazirinone (1) in either the
      condensed phase (using matrix isolation spectroscopy) or in the gas phase (using
      millimeter-wave rotational spectroscopy), however, have been unsuccessful.
      Trapping the volatile products produced from the reaction of 3-chloro-3-(p
      nitrophenoxy)diazirine (5) with tetrabutylammonium fluoride (TBAF) under matrix
      isolation conditions affords chlorofluorodiazirine (8) and carbon monoxide but
      fails to provide evidence for diazirinone (1). Moreover, sophisticated ab initio
      calculations of the structure and fundamental vibrational frequencies of
      diazirinone (1) produce an estimate for the fundamental band origin of the C=O
      stretch (2046 cm(-1)) that is ca. 100 cm(-1) lower in frequency than the
      experimental value previously attributed to this band. This discrepancy lies well
      outside any expected solvent shift or calculation error at this level of theory.
      In an effort to reconcile our findings with the earlier reports concerning
      diazirinone (1), we reconsidered the infrared spectral evidence upon which the
      original claim of diazirinone synthesis was based. New experiments demonstrate
      that these spectra may be explained and reproduced with a combination of solution
      phase and gas-phase absorptions of CO, without recourse to invoke diazirinone
      (1).

PMID- 20151693
TI  - Fabrication of honeycomb-structured porous surfaces decorated with glycopolymers.
AB  - We prepared breath figure patterns on functional surfaces by the surface
      segregation of a statistical glycopolymer, (styrene-co-2-(D-glucopyranosyl)
      aminocarbonyloxy ethyl acrylate (S-HEAGl). The synthesis of the statistical
      glycopolymer is prepared in a straightforward approach by conventional free
      radical copolymerization of styrene and the unprotected glycomonomer. Blends of
      this copolymer and high-molecular-weight polystyrene were spin coated from THF
      solutions, leading to the formation of surfaces with both controlled
      functionality and topography. AFM studies revealed that both the composition of
      the blend and the relative humidity play key roles in the size and distribution
      of the pores at the interface. Thus, the topographical features obtained on the
      polymer surfaces during film preparation by the breath figure methodology varied
      from 200 to 700 nm. Moreover, this approach leads to porous films in which the
      hydrophilic glycomonomer units are oriented toward the pore interface because
      upon soft annealing in water the holes are partially swelled. The self
      organization of the glycopolymer within the pores was additionally confirmed by
      the reaction of carbohydrate hydroxyl groups with rhodamine isocyanate. Equally,
      we demonstrate the bioactivity of the anchored glycopolymers by means of the
      lectin binding test using concanavalin A (Con A).

PMID- 20151694
TI  - Why does binding of proteins to DNA or proteins to proteins not necessarily spell
      function?
AB  - Studies of binding are often question: first, is the observed binding functional,
      and second, if it is, which function? Is it activation or repression? The first
      question relates to binding at different sites; the second relates to binding at
      similar sites. These questions apply to transcription factors binding to genomic
      DNA and to protein interaction domains binding to their partners. Here, we
      explain that both can be understood in terms of allostery and the cellular (or in
      vitro) environment. The idea is simple yet powerful; it emphasizes the role of
      allostery in defining whether binding between transcription factors and (cognate
      or noncognate) DNA sequences will lead to function and to the type of function.
      Allosteric effects are the outcome of dynamically shifting populations; thus
      binding to even slightly different DNA sequences will lead to different
      transcription factor conformations that can be reflected in the binding sites to
      their co-regulators. Currently, allostery is not considered when trying to
      understand how binding phenomena determine the functional outcome. Allosteric
      effects can enhance the binding specificity in a function-oriented manner. Here
      we provide a biological rationale that considers cellular crowding effects.

PMID- 20151695
TI  - The mechanism of nucleophilic displacements at phosphorus in chloro-substituted
      methylphosphonate esters: P-O vs P-C bond cleavage: a DFT study.
AB  - Potential energy surfaces for the nucleophilic displacements at phosphorus in
      dimethyl methyl-, chloromethyl-, dichloromethyl-, and trichloromethylphosphonates
      have been computed at the B3LYP/6-31+G* level of theory, using IEF-PCM to account
      for the solvent effect. The results reveal that sequential addition of chlorine
      substituents on the methyl phosphonates increases the stability of transition
      states and intermediates which facilitate P-C bond cleavage. Thus, while
      nonsubstituted dimethyl methylphosphonate and dimethyl chloromethylphosphonate
      may undergo exclusive P-O bond cleavage, the trichlorinated analogue exclusively
      undergoes P-C bond dissociation. Dichloromethylphosphonic acid derivatives were
      found to be borderline cases: while P-O fission is the preferred process, P-C
      scission might also be feasible. The increase in stability of the corresponding
      transition states and intermediates can account for the enhancement in the
      apicophilicity of the methyl ligand upon substitution with chlorine atoms.

PMID- 20151696
TI  - Electrokinetic concentration of DNA polymers in nanofluidic channels.
AB  - DNA molecules can be concentrated in a narrow region of a nanochannel when driven
      electrokinetically in submillimolar salt solutions. Transport experiments and
      theoretical modeling reveal the interplay of electrophoresis, electro-osmosis,
      and the unique statistical properties of confined polymers that lead to DNA
      aggregation. A finite conductance through the bulk of the device also plays a
      crucial role by influencing the electric fields in the nanochannel. We build on
      this understanding by demonstrating how a nanofluidic device with integrated
      electrodes can preconcentrate DNA at selected locations and at physiological salt
      concentrations that are relevant to lab-on-a-chip applications.

PMID- 20151697
TI  - Quantum interference channeling at graphene edges.
AB  - Electron scattering at graphene edges is expected to make a crucial contribution
      to the electron transport in graphene nanodevices by producing quantum
      interferences. Atomic-scale scanning tunneling microscopy (STM) topographies of
      different edge structures of monolayer graphene show that the localization of the
      electronic density of states along the C-C bonds, a property unique to monolayer
      graphene, results in quantum interference patterns along the graphene carbon bond
      network, whose shapes depend only on the edge structure and not on the electron
      energy.

PMID- 20151698
TI  - Trapping and sensing 10 nm metal nanoparticles using plasmonic dipole antennas.
AB  - The optical trapping of Au nanoparticles with dimensions as small as 10 nm in the
      gap of plasmonic dipole antennas is demonstrated. Single nanoparticle trapping
      events are recorded in real time by monitoring the Rayleigh scattering spectra of
      individual plasmonic antennas. Numerical simulations are also performed to
      interpret the experimental results, indicating the possibility to trap
      nanoparticles only a few nanometers in size. This work unveils the potential
      associated with the integration of plasmonic trapping with localized surface
      plasmon resonance based sensing techniques, in order to deliver analyte to
      specific, highly sensitive regions ("hot spots").

PMID- 20151699
TI  - Solvent dependence of the kinetic isotope effect in the reaction of ascorbate
      with the 2,2,6,6-tetramethylpiperidine-1-oxyl radical: tunnelling in a small
      molecule reaction.
AB  - The oxidation of ascorbate with the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)
      radical in water and water-dioxane mixed solvent has been demonstrated to be a
      proton-coupled electron transfer (PCET) process, involving hydrogen tunnelling at
      room temperature. The magnitude of the kinetic isotope effect (KIE) k(H)/k(D) in
      the reaction increases with decrease of the solvent polarity. The evidence
      comprise: (a) the spectroscopic and kinetic evidence for the interaction of
      ascorbate and TEMPO; (b) the observation of KIEs k(H)/k(D) of 24.2(0.6) in water
      and 31.1(1.1) in 1:1 v/v water-diox. (diox = dioxane), at 298 K; (c) the
      observation of isotope effect on the Arrhenius prefactor, A(H)/A(D) of 0.6(0.2)
      in the reaction in water and 1.2(0.2) in 1:1 v/v water-diox solvent; (d) the
      observation of isotope differences in the enthalpies of activation in water and
      D(2)O, Delta(r)H(double dagger) (in H(2)O) = 31.0(0.4) kJ/mol, Delta(r)H(double
      dagger) (in D(2)O) = 40.0 (0.5) kJ/mol; in 1:1 v/v water-diox and 1:1 v/v D(2)O
      diox, Delta(r)H(double dagger) (in H(2)O/diox) = 23.9(0.2) kJ/mol,
      Delta(r)H(double dagger) (in D(2)O/diox) = 32.1(0.3) kJ/mol; (e) the temperature
      dependence of the KIEs in water and 1:1 v/v water-dioxane; these KIEs range from
      27.3 at 285.4 K to 19.1 at 317.4 K in water and from 34.3 to 24.6 at the
      corresponding temperatures in 1:1 v/v water-diox, respectively; (f) the
      observation of an increase of the KIE in 10-40% v/v dioxane-water solvents
      relative to the KIE in water alone. There is a weak solvent dependence of the
      rate constant on going from water to 1:1 v/v water-diox. solvent, from 2.20(0.03)
      mol(-1) dm(3) s(-1) to 5.50(0.14) mol(-1) dm(3) s(-1), respectively, which
      originates from the mutual compensation of the enthalpy and entropy of
      activation.

PMID- 20151700
TI  - Identification of descriptors for the CO interaction with metal nanoparticles.
AB  - The design and performance optimization of future nanocatalysts will depend on
      our understanding of adsorbate-metal interactions. Using first principle
      calculations, we identify suitable descriptors, namely, the coordination number
      and curvature angle of the surface Au atoms, capable of predicting the CO binding
      strength on every site of Au nanoparticles. Our results unravel how the size,
      shape, and symmetry of nanoparticles affect their electronic properties and,
      consequently, their interaction with CO. Importantly, these descriptors can be
      successfully applied to other metals using structural inputs from experiments
      and/or molecular modeling.

PMID- 20151701
TI  - Size effect on fragmentation in tandem mass spectrometry.
AB  - The collision energy or collision voltage necessary to obtain 50% fragmentation
      (characteristic collision energy/voltage, CCE or CCV) has been systematically
      determined for different types of molecules [poly(ethylene glycols) (PEG),
      poly(tetrahydrofuran) (PTHF), and peptides] over a wide mass (degrees of freedom)
      range. In the case of lithium-cationized PEGs a clear linear correlation (R(2) >
      0.996) has been found between CCE and precursor ion mass on various instrument
      types up to 4.5 kDa. A similar linear correlation was observed between CCV and
      the mass-to-charge ratio. For singly and multiply charged polymers studied under
      a variety of experimental conditions and on several instruments, all data were
      plotted together and showed correlation coefficient R(2) = 0.991. A prerequisite
      to observe such a good linear correlation is that the energy and entropy of
      activation in a class of polymers is likely to remain constant. When compounds of
      different structure are compared, the CCV will depend not only on the molecular
      mass but the activation energy and entropy as well. This finding has both
      theoretical and practical importance. From a theoretical point of view it
      suggests fast energy randomization up to at least 4.5 kDa so that statistical
      rate theories are applicable in this range. These results also suggest an easy
      method for instrument tuning for high-throughput structural characterization
      through tandem MS: after a standard compound is measured, the optimum excitation
      voltage is in a simple proportion with the mass of any structurally similar
      analyte at constant experimental conditions.

PMID- 20151702
TI  - Gold nanoparticle self-assembly in saturated phospholipid monolayers.
AB  - Self-assembly of nanostructures on surfaces is a promising area in the emerging
      field of "bottom-up nanolithography". We describe a systematic analysis of
      hydrophobically capped gold nanoparticle (Au NP) assemblies created within
      monolayers of saturated phospholipids deposited at the air/water interface. We
      show that the Au NPs are segregated within the mixed monolayers, forming distinct
      configurations. Microscopy analysis reveals that organized Au NP aggregates,
      including wires, rings, and "doughnut-shape" structures, are observed only within
      condensed-phase monolayers comprising phospholipids exhibiting longer acyl side
      chains. In these monolayers, the Au NPs are localized at the edges of the
      condensed phospholipid domains. In addition to the pronounced effect of the
      phospholipid phases at the air/water interface, NP organization was found to
      depend upon the hydrophobic capping agents of the particles. The Au
      nanostructures assembled at the air/water interface can be transferred onto solid
      substrates, suggesting that the self-assembly monolayer approach could be
      exploited for practical nanoelectronic and sensing applications.

PMID- 20151703
TI  - End-to-surface reaction dynamics of a single surface-attached DNA or polypeptide.
AB  - The dynamics of surface-attached polymers play a key role in the operation of a
      number of biological sensors, yet its current understanding is rather limited.
      Here we use computer simulations to study the dynamics of a reaction between the
      free end of a polymer chain and a surface, to which its other end has been
      attached. We consider two limiting cases, the diffusion-controlled limit, where
      the reaction is accomplished whenever the free chain end diffuses to within a
      specified distance from the surface, and the reaction-controlled limit, where
      slow, intrinsic reaction kinetics rather than diffusion of the chain is rate
      limiting. In the diffusion-controlled limit, we find that the overall rate scales
      as N(-b), where N is the number of monomers in the chain and b approximately =
      2.2 for excluded volume chains. This value of the scaling exponent b is close to
      that derived from a simple approximate theory treating the dynamics of the chain
      end relative to the surface as one-dimensional diffusion in an effective
      potential. In the reaction-controlled limit, the value of the scaling exponent b
      is close to 1. We compare our findings with those for the related (and better
      studied) problem of end-to-end reactions within an unconstrained polymer chain
      and discuss their implications for electrochemical DNA sensors.

PMID- 20151704
TI  - Meaningful differences in spectral performance, thermal behavior, and
      heterogeneous catalysis between ammonium molybdate tetrahydrate and its adduct of
      beta-cyclodextrin.
AB  - A novel molecule-ion adduct of ammonium molybdate tetrahydrate (AMT) with beta
      cyclodextrin (CD) was prepared in this work. Significant differences in spectral
      properties between AMT and the adduct AMT-beta-CD were observed by a series of
      experimental probes, such as powder X-ray diffraction, Fourier transformation
      infrared spectroscopy, and Raman spectroscopy. Field emission scanning electron
      microscopy showed that, although the crystal growth of AMT-beta-CD was dominated
      by the molecular stacking of AMT, the size and morphology of the adduct were
      rather different from those seen in free AMT. The difference in stacking forms
      was attributed to the contribution of the molecule-ion interaction between AMT
      and beta-CD. A drastic improvement in thermal stability of AMT and beta-CD after
      adduct formation was observed by thermogravimetry analysis, which was confirmed
      by controlled sintering measurements. This revealed that the adduct interaction
      between them played an important role in mediating the thermal decomposition
      process of the adducted components. Furthermore, our results indicated that AMT
      and its adduct had a different performance in the catalytic desulfurization of
      thiophene and its derivatives. The fact that the catalytic efficiency of AMT was
      decreased after adduct formation implied there was a complexation between AMT and
      beta-CD. Besides, several unusual molecular ions--NH(3)(+), NH(2)(+), and NH(+)-
      were simultaneously found with gas chromatography coupled to time-of-flight mass
      spectrometry of free AMT.

PMID- 20151705
TI  - Ab initio elasticity of poly(lactic acid) crystals.
AB  - We investigate the elastic properties of poly(lactic acid) crystals using a first
      principles pseudopotential plane wave method within the generalized gradient
      approximation of the density functional theory. Stiffness and compliance matrices
      of poly(l-lactic acid) (PLLA) alpha- and beta-forms, and the stereocomplex (sc)
      between PLLA and poly(D-lactic acid) (PDLA) (50:50) sc-form are calculated using
      the finite strain technique. The results indicate that crystalline poly(lactic
      acid) is highly mechanical anisotropic. Contributions from the crystalline phase
      to the anisotropy of the elastic modulus in an uniaxially oriented poly(lactic
      acid) fiber are estimated on the basis of a cylindrically symmetric
      polycrystalline aggregate model. Both symmetry and orientation distribution of
      the crystals have been taken into account. Voigt and Reuss bounds of Young's
      moduli and shear moduli and Poisson's ratio are calculated from single crystal
      elastic properties.

PMID- 20151706
TI  - Cooperative preassociation stages of PEO-PPO-PEO triblock copolymers: NMR and
      theoretical study.
AB  - Using (1)H and (13)C 1D and 2D NMR spectra, pulsed field-gradient (PFG) diffusion
      measurements, and (13)C relaxations supported by density functional theory (DFT)
      calculations, the temperature-dependent behavior of (EO)(m)(PO)(n)(EO)(m) block
      copolymers (m/n = 31/14, 31/72, and 17/1) in D(2)O below and at the critical
      micellar temperature (CMT) was investigated in order to understand the nature of
      primary self-association acts and their true driving force. It was shown that a
      conformation change of the PO block followed by mild and reversible association
      with other PO blocks and eventually with the inner parts of EO blocks starts at
      temperatures 10-12 K below the CMT. The primary process is the entropy-driven
      disintegration of the PPO hydration envelope based on cooperation of hydrophobic
      hydration and hydrogen bonding. The partial dehydration of PPO is followed by its
      conformation change. Both processes are cooperative and reversible with a
      correlation time of the order 0.01 s and an activation energy of 51.3 kJ/mol. The
      PPO chain in a staggered conformation is prone to self-association starting at
      temperatures 5-6 K below CMT. In (EO)(m)(PO)(n)(EO)(m) block copolymers, this
      process is complicated by the stripping of PEO chains of a part of hydrogen-bound
      water and entwining them with PPO. It is shown that only inner (PPO-near) parts
      of PEO take part in the process, the end-groups remaining free.

PMID- 20151708
TI  - Development of a visible-light-sensitized europium complex for time-resolved
      fluorometric application.
AB  - The time-resolved luminescence bioassay technique using luminescent lanthanide
      complexes as labels is a highly sensitive and widely used bioassay method for
      clinical diagnostics and biotechnology. A major drawback of the current technique
      is that the luminescent lanthanide labels require UV excitation (typically less
      than 360 nm), which can damage living biological systems and is holding back
      further development of time-resolved luminescence instruments. Herein we describe
      two approaches for preparing a visible-light-sensitized Eu(3+) complex in aqueous
      media for time-resolved fluorometric applications: a dissociation enhancement
      aqueous solution that can be excited by visible light for
      ethylenediaminetetraacetate (EDTA)-Eu(3+) detection and a visible-light
      sensitized water-soluble Eu(3+) complex conjugated bovine serum albumin (BSA) for
      biolabeling and time-resolved luminescence bioimaging. In the first approach, a
      weakly acidic aqueous solution consisting of 4,4'-bis(1'',1'',1'',2'',2'',3'',3''
      heptafluoro-4'',6''-hexanedion-6''-yl)-o-terphenyl (BHHT), 2-(N,N-diethylanilin-4
      yl)-4,6-bis(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine (DPBT), and Triton X-100 was
      prepared. This solution shows a strong luminescence enhancement effect for EDTA
      Eu(3+) with a wide excitation wavelength range from UV to visible light (a
      maximum at 387 nm) and a long luminescence lifetime (520 micros), to provide a
      novel dissociation enhancement solution for time-resolved luminescence detection
      of EDTA-Eu(3+). In the second approach, a ternary Eu(3+) complex, 4,4'
      bis(1'',1'',1'',2'',2'',3'',3''-heptafluoro-4'',6''-hexanedion-6''-yl)
      chlorosulfo-o-terphenyl (BHHCT)-Eu(3+)-DPBT, was covalently bound to BSA to form
      a water-soluble BSA-BHHCT-Eu(3+)-DPBT conjugate. This biocompatible conjugate is
      of the visible-light excitable feature in aqueous media with a wide excitation
      wavelength range from UV to visible light (a maximum at 387 nm), a long
      luminescence lifetime (460 micros), and a higher quantum yield (27%). The
      conjugate was successfully used for streptavidin (SA) labeling and time-resolved
      luminescence imaging detection of three environmental pathogens, Giardia lamblia
      , Cryptosporidium muris , and Cryptosporidium parvum , in water samples. Our
      strategy gives a general idea for designing a visible-light-sensitized Eu(3+)
      complex for time-resolved luminescence bioassay applications.

PMID- 20151707
TI  - Replacement of Val3 in human thymidylate synthase affects its kinetic properties
      and intracellular stability .
AB  - Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal
      extension of approximately 27 amino acids that is not present in bacterial TSs.
      The extension, which is disordered in all reported crystal structures of TSs, has
      been considered to play a primary role in protein turnover but not in catalytic
      activity. In mammalian cells, the variant V3A has a half-life similar to that of
      wild-type human TS (wt hTS) while V3T is much more stable; V3L, V3F, and V3Y have
      half-lives approximately half of that for wt hTS. Catalytic turnover rates for
      most Val3 mutants are only slightly diminished, as expected. However, two
      mutants, V3L and V3F, have strongly compromised dUMP binding, with K(m,app)
      values increased by factors of 47 and 58, respectively. For V3L, this observation
      can be explained by stabilization of the inactive conformation of the loop of
      residues 181-197, which prevents substrate binding. In the crystal structure of
      V3L, electron density corresponding to a leucine residue is present in a position
      that stabilizes the loop of residues 181-197 in the inactive conformation. Since
      this density is not observed in other mutants and all other leucine residues are
      ordered in this structure, it is likely that this density represents Leu3. In the
      crystal structure of a V3F.FdUMP binary complex, the nucleotide is bound in an
      alternative mode to that proposed for the catalytic complex, indicating that the
      high K(m,app) value is caused not by stabilization of the inactive conformer but
      by substrate binding in a nonproductive, inhibitory site. These observations show
      that the N-terminal extension affects the conformational state of the hTS
      catalytic region. Each of the mechanisms leading to the high K(m,app) values can
      be exploited to facilitate design of compounds acting as allosteric inhibitors of
      hTS.

PMID- 20151709
TI  - Regio-defined amino[5]oxa- and thiahelicenes: a dramatic impact of the nature of
      the heteroatom on the helical shape and racemization barriers.
AB  - The present approach to heterohelicenes provides original [5]oxa- and
      thiahelicenes, where both oxygen and sulfur atoms are located at the end of the
      inner helix. Quantum chemical calculations are carried out to determine the
      pathway for interconversion between two enantiomers and demonstrate that the
      energy barrier is strongly dependent on the nature of the heteroatom present on
      the helical shape.

PMID- 20151710
TI  - Efficient and regioselective synthesis of 5-hydroxy-2-isoxazolines: versatile
      synthons for isoxazoles, beta-lactams, and gamma-amino alcohols.
AB  - An efficient and highly regioselective protocol was developed for the preparation
      of 5-hydroxy-2-isoxazolines, which have been proved to be versatile synthons for
      isoxazles, beta-hydroxy oximes, and gamma-amino alcohols. Beta-lactams, commonly
      embedded in the skeletons of bioactive natural products, were also synthesized in
      two steps from beta-hydroxy oximes, providing a new strategy for the synthesis of
      this kind of compounds.

PMID- 20151711
TI  - A practical chemo-enzymatic synthesis of homochiral bicyclo[2.2.2]octane-2,5
      dione.
AB  - A practical synthetic route for the preparation of chiral bicyclo[2.2.2]octane
      2,5-dione, the precursor of useful chiral diene ligands, was realized via Diels
      Alder reaction and resolution of an enol acetate derivative by immobilized
      lipases.

PMID- 20151712
TI  - Generation and intermolecular trapping of 1,2-diaza-4-silacyclopentane-3,5-diyls
      in the denitrogenation of 2,3,5,6-tetraaza-7-silabicyclo[2.2.1]hept-2-ene: an
      experimental and computational study.
AB  - In our previous computational study, we found that silicon and nitrogen atoms
      have a notable effect on the reactivity of 1,2-diaza-4-silacyclopentane-3,5
      diyls. Thus, the singlet state of the diradical was calculated to be much more
      stable than the corresponding ring-closing product, i.e., 2,3-diaza-5
      silabicyclo[2.1.0]pentane, and the triplet state of the diradical. In the present
      study, derivatives of the diradical were generated experimentally in the
      denitrogenation of precursor azoalkanes, i.e., 2,3,5,6-tetraaza-7
      silabicyclo[2.2.1]hept-2-enes, which can be prepared by cycloaddition of a
      diazasilole with 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) or 4-methyl-1,2,4
      triazole-3,5-dione (MTAD). The diradicals were trapped intermolecularly to afford
      polycyclic compounds. The computational studies (UB3LYP/6-31G*) of the
      denitrogenation of a model azoalkane suggested that stepwise denitrogenation with
      an activation energy of ca. 22 kcal/mol is the thermodynamically favored pathway
      for generation of the singlet diradical 1,2-diaza-4-silacyclopentane-3,5-diyl
      derivative via a 1,4-diazenyldiradical intermediate. The low activation energy of
      the denitrogenation reaction was consistent with the experimental observation
      that the azoalkane was labile under the preparation conditions used in this
      study.

PMID- 20151713
TI  - Adsorption of egg phosphatidylcholine to an air/water and triolein/water bubble
      interface: use of the 2-dimensional phase rule to estimate the surface
      composition of a phospholipid/triolein/water surface as a function of surface
      pressure.
AB  - Phospholipid monolayers play a critical role in the structure and stabilization
      of biological interfaces, including all membranes, the alveoli of the lungs, fat
      droplets in adipose tissue, and lipoproteins. The behavior of phospholipids in
      bilayers and at an air-water interface is well understood. However, the study of
      phospholipids at oil-water interfaces is limited due to technical challenges. In
      this study, egg phosphatidylcholine (EPC) was deposited from small unilamellar
      vesicles onto a bubble of either air or triolein (TO) formed in a low-salt
      buffer. The surface tension (gamma) was measured using a drop tensiometer. We
      observed that EPC binds irreversibly to both interfaces and at equilibrium exerts
      approximately 12 and 15 mN/m of pressure (Pi) at an air and TO interface,
      respectively. After EPC was bound to the interface, the unbound EPC was washed
      out of the cuvette, and the surface was compressed to study the Pi/area
      relationship. To determine the surface concentration (Gamma), which cannot be
      measured directly, compression isotherms from a Langmuir trough and drop
      tensiometer were compared. The air-water interfaces had identical characteristics
      using both techniques; thus, Gamma on the bubble can be determined by overlaying
      the two isotherms. Both TO and EPC are surface-active, so in a mixed TO/EPC
      monolayer, both molecules will be exposed to water. Since TO is less surface
      active than EPC, as Pi increases, the TO is progressively ejected. To understand
      the Pi/area isotherm of EPC on a TO bubble, a variety of TO-EPC mixtures were
      spread at the air-water interface. The isotherms show an abrupt break in the
      curve caused by the ejection of TO from the monolayer into a new bulk phase. By
      overlaying the compression isotherm above the ejection point with a TO bubble
      compression isotherm, Gamma can be estimated. This allows determination of Gamma
      of EPC on a TO bubble as a function of Pi.

PMID- 20151714
TI  - One-pot synthesis of chromenylfurandicarboxylates and
      cyclopenta[b]chromenedicarboxylates involving zwitterionic intermediates. A DFT
      investigation on the regioselectivity of the reaction.
AB  - The reaction of 1:1 zwitterionic intermediates generated in situ from either tert
      butylisocyanide or cyclohexylisocyanide and acetylenedicarboxylates with 3
      formylchromones is described, whereupon either chromenylfurandicarboxylates or
      cyclopenta[b]chromenedicarboxylates are formed, depending on the nature of the
      chromone 6-position substituent and also on the acetylene ester group. In
      addition, from the reaction with a 1:2 zwitterionic intermediate,
      cyclohepta[b]chromenetetracarboxylates are isolated. The regioselectivity of the
      reaction was also investigated by DFT calculations. The geometries of the
      reactants, intermediate zwitterions, transition structures, and intermediate
      products, leading to the final products, were optimized using the B3LYP
      functional with the 6-31G(d) basis set. The structures of the products were
      elucidated by 1D and 2D NMR experiments. Full assignment of all (1)H and (13)C
      NMR chemical shifts has been achieved. Plausible mechanistic schemes are
      provided.

PMID- 20151715
TI  - Universal aptameric system for highly sensitive detection of protein based on
      structure-switching-triggered rolling circle amplification.
AB  - A universal approach is proposed in this study for the development of an
      aptameric assay system for proteins based on aptamer structure-switching
      triggered ligation-rolling circle amplification (L-RCA) upon target binding. The
      strategy chiefly depends on the competition for binding the aptamer probe between
      target protein and a complementary single-stranded DNA (CDNA) that can induce the
      circularization of the padlock probe. Introduction of target protein into the
      assay system inhibits the hybridization of the CDNA with the aptamer probe
      because of the formation of the target/aptamer duplex. The free CDNA can only
      hybridize with the padlock probe. With the assistance of DNA ligase, the padlock
      probe is circularized, and the subsequent RCA process can be accomplished by Phi
      29 DNA polymerase. Each RCA product containing thousands of repeated sequences
      might hybridize with a large number of molecular beacons (detection probes),
      resulting in an enhanced fluorescence signal. In contrast, in the absence of
      target protein, no obvious change in the fluorescence intensity of the detection
      probe is observed. This signaling mode for target recognition and transduction
      events is based on the combination of aptamer recognition elements and L-RCA
      technology with high specificity and sensitivity. The proposed assay system not
      only exhibits excellent analytical characteristics (e.g., the detection limit on
      attomolar scale and a linear dynamic range of more than 3 orders of magnitude)
      but also possesses significant advantages over existing aptameric assays. The
      proposed strategy is universal since the sequences of aptamer probe, CDNA, and
      padlock probe could be easily designed to be compatible with the L-RCA based
      detection of other proteins without other conditions.

PMID- 20151716
TI  - One-pot synthesis of linearly fused N-heterocyles from their angular analogues
      and studies of their redox and electrochromic properties.
AB  - In an unusual chemical transformation, the angular heterocyclic compound
      [1]ClO(4), upon reaction with a primary aromatic amine, is transformed to a
      linear heterocyclic compound 3 via the angular intermediate [2]ClO(4) in one pot.
      Characterization of the compounds was primarily achieved by (1)H and (13)C NMR
      and mass spectral data. Analyses of single-crystal X-ray structures of the
      representative compounds confirmed their identities. These compounds exhibit
      notable spectral and redox properties. Their redox behavior is followed by
      spectral characterization of the electro-generated radicals. Electrochromic
      properties of the reference compounds are also explored.

PMID- 20151717
TI  - Solid state 2H NMR analysis of furanose ring dynamics in DNA containing uracil.
AB  - DNA damage has been implicated in numerous human diseases, particularly cancer,
      and the aging process. Single-base lesions, such as uracil, in DNA can be
      cytotoxic or mutagenic and are recognized by a DNA glycosylase during the process
      of base excision repair. Increased dynamic properties in lesion-containing DNAs
      have been suggested to assist recognition and specificity. Deuterium solid-state
      nuclear magnetic resonance (SSNMR) has been used to directly observe local
      dynamics of the furanose ring within a uracil:adenine (U:A) base pair and
      compared to a normal thymine:adenine (T:A) base pair. Quadrupole echo lineshapes,
      <T(1Z)>, and <T(2e)> relaxation data were collected, and computer modeling was
      performed. The results indicate that the relaxation times are identical within
      the experimental error, the solid lineshapes are essentially indistinguishable
      above the noise level, and our lineshapes are best fit with a model that does not
      have significant local motions. Therefore, U:A base pair furanose rings appear to
      have essentially identical dynamic properties as a normal T:A base pair, and the
      local dynamics of the furanose ring are unlikely to be the sole arbiter for
      uracil recognition and specificity in U:A base pairs.

PMID- 20151720
TI  - Introduction: mechanisms of metal toxicity special issue.

PMID- 20151718
TI  - Identification of novel protein kinase A phosphorylation sites in the M-domain of
      human and murine cardiac myosin binding protein-C using mass spectrometry
      analysis.
AB  - Cardiac myosin binding protein-C (cMyBP-C) is a large multidomain accessory
      protein bound to myosin thick filaments in striated muscle sarcomeres. It plays
      an important role in the regulation of muscle contraction, and mutations in the
      gene encoding cMyBP-C are a common cause of familial hypertrophic cardiomyopathy,
      the leading cause of sudden cardiac death in young people. (1) The N-terminal
      domains including the C0, C1, cMyBP-C motif, and C2 domains play a crucial role
      in maintaining and modulating actomyosin interactions (keeping normal cardiac
      function) in a phosphorylation-dependent manner. The cMyBP-C motif or "M-domain"
      is a highly conserved linker domain in the N-terminus of cMyBP-C that contains
      three to five protein kinase A (PKA) phosphorylation sites, depending on species.
      For the human isoform, three PKA sites were previously identified (Ser(275),
      Ser(284), and Ser(304)), while three homologous sites exist in the murine isoform
      (Ser(273), Ser(282), and Ser(302)). The murine cMyBP-C isoform contains an
      additional conserved consensus site, Ser(307) that is not present in the human
      isoform. In this study, we investigated sites of PKA phosphorylation of murine
      and human cMyBP-C by treating the recombinant protein C0C2 ( approximately 50
      KDa, which contains the N-terminal C0, C1, M, and C2 domains) and C1C2
      (approximately 35 KDa, contains C1, M, and C2 domains) with PKA and assessing the
      phosphorylation states using SDS-PAGE with ProQ Diamond staining, and powerful
      hybrid mass spectrometric analyses. Both high-accuracy bottom-up and measurements
      of intact proteins mass spectrometric approaches were used to determine the
      phosphorylation states of C0C2 and C1C2 proteins with or without PKA treatment.
      Herein, we report for the first time that there are four PKA phosphorylation
      sites in both murine and human M-domains; both murine Ser(307) and a novel human
      Ser(311) can be phosphorylated in vitro by PKA. Future studies are needed to
      investigate the phosphorylation state of murine and human cMyBP-C in vivo.

PMID- 20151723
TI  - Measuring quality of life for certain events versus pre-specified points in time.

PMID- 20151724
TI  - The cost effectiveness of rufinamide in the treatment of Lennox-Gastaut syndrome
      in the UK.
AB  - Lennox-Gastaut syndrome (LGS) is a catastrophic childhood form of epilepsy. The
      syndrome is characterized by mental impairment, frequent seizures of multiple
      types that are particularly resistant to treatment, and high rates of seizure
      related injury. With the introduction of newer, but more costly, antiepileptic
      drugs (AEDs), it is important that decision makers are able to assess their value
      in the management of this rare and difficult-to-treat condition. To evaluate the
      cost effectiveness, from the UK NHS perspective, of rufinamide in patients with
      LGS. An individual patient-simulation model was developed to estimate the total
      treatment-related costs and clinical benefits of rufinamide compared with
      topiramate and lamotrigine over a 3-year time horizon. The model examines the
      treatment scenarios of adding rufinamide, lamotrigine or topiramate to older AEDs
      (standard therapy), or standard therapy alone within a primary-care or community
      setting. Three placebo-controlled clinical trials of adjunctive AED treatment for
      children with LGS were analysed. There are no head-to-head comparator studies.
      Between 98 and 139 patients were randomized in each study and the mean age in
      each study was 10, 11 and 14 years. A mixed-treatment comparison using a random
      effects model was carried out on the number of patients in each response
      category, using the placebo arms of the respective trials. The primary outcome
      measure was the percentage of successfully treated patients, defined as >50%
      reduction in the frequency of total seizures and drop attacks. The hypothesis
      being tested was formulated after data collection. Costs ( pound, year 2006/07
      values) of patient monitoring, switching treatments, hospitalization due to
      seizure, treatment of adverse effects, and personal and social services were
      included in the analysis. Results of 10,000 Monte Carlo simulations were
      bootstrapped to conduct probabilistic sensitivity analysis. Over 3 years,
      adjunctive rufinamide resulted in higher total costs than topiramate and
      lamotrigine; however, with more patients being treated successfully, this leads
      to acceptable incremental cost-effectiveness ratios. If society is prepared to
      pay at least 250 pounds for a 1% increase in the number of successfully treated
      LGS patients, in terms of a 50% reduction in the frequency of drop attacks, the
      probability of the treatment with rufinamide being cost effective is >80%. This
      cost-effectiveness analysis suggests that rufinamide results in more LGS patients
      being treated successfully at a reasonable cost from a UK NHS perspective.

PMID- 20151725
TI  - Estimation of a valuation function for a diabetes mellitus-specific preference
      based measure of health: the Diabetes Utility Index.
AB  - Preference-based measures of health (PBMH) provide 'preference' or 'utility'
      weights that enable the calculation of QALYs for the economic evaluations of
      interventions. The Diabetes Utility Index (DUI) was developed as a brief, self
      administered, diabetes mellitus-specific PBMH that can efficiently estimate
      patient-derived health state utilities. To describe the development of the
      valuation function for the DUI, and to report the validation results of the
      valuation function. Multi-Attribute Utility Theory (MAUT) was used as the
      framework to develop a valuation function for the DUI. Twenty of 768 possible
      health states of the DUI classified as anchor states, single-attribute level
      states including corner states, and marker states were selected and described for
      preference elicitation interviews. Visual analogue scale and standard gamble (SG)
      exercises were used to measure preferences from individuals with diabetes
      recruited from primary care and community settings in and around Morgantown, WV,
      USA for the 20 health states defined by combinations of DUI attributes and
      severity levels. Data collected in the interviews were used to develop a
      valuation function that calculates utilities for the DUI health states and
      calculates attribute-level utilities. A validation survey of the valuation
      function was conducted in collaboration with the West Virginia University (WVU)
      Diabetes Institute. A total of 100 individuals with diabetes were interviewed and
      their preferences for various DUI health states measured. From data generated in
      the interviews, a DUI valuation function was developed on a scale where 1.00 =
      perfect health (PH) and 0.00 = the all worse 'pits' state, and adjusted to yield
      utilities on the conventional scale 1.00 = PH and 0.00 = dead. A total of 396
      patients with diabetes who received care at WVU clinics completed a DUI mail
      validation survey (response rate = 33%). Clinical data consisting of
      International Classification of Diseases, 9th edition, diagnosis codes and
      glycosylated haemoglobin (HbA(1c)) values for the respondents were merged with
      their responses to the DUI. The utilities calculated by the scoring function of
      the DUI compared favourably to cardinal SG utilities for three DUI health states
      for which both assessments were available. The DUI utility function slightly
      underestimated actual SG utilities for mild and moderate health states (mean
      absolute difference = 0.05). There was a small but significant correlation
      between DUI utility scores and average past year HbA(1c) values (r = -0.30; p <
      0.001). Respondents with two or more complications had significantly lower DUI
      utilities than those with no complications (p < 0.001) or one complication (p =
      0.015). Insulin users had significantly lower DUI utilities than non-users (p <
      0.001), and those with HbA(1c) values <7% had significantly higher DUI utilities
      than those with HbA(1c) values of >or=7% (p < 0.001). No significant association
      was found between DUI scores and age or sex. These results show evidence of the
      feasibility and validity of the DUI. Further research is suggested to demonstrate
      the generalizability of these findings, to study the responsiveness of the DUI,
      and to examine the clinical meaningfulness of DUI change scores.

PMID- 20151728
TI  - On the linear response and scattering of an interacting molecule-metal system.
AB  - A many-body Green's function approach to the microscopic theory of plasmon
      enhanced spectroscopy is presented within the context of localized surface
      plasmon resonance spectroscopy and applied to investigate the coupling between
      quantum-molecular and classical-plasmonic resonances in monolayer-coated silver
      nanoparticles. Electronic propagators or Green's functions, accounting for the
      repeated polarization interaction between a single molecule and its image in a
      nearby nanoscale metal, are explicitly computed and used to construct the linear
      response properties of the combined molecule-metal system to an external
      electromagnetic perturbation. Shifting and finite lifetime of states appear
      rigorously and automatically within our approach and reveal an intricate coupling
      between molecule and metal not fully described by previous theories. Self
      consistent incorporation of this quantum-molecular response into the continuum
      electromagnetic scattering of the molecule-metal target is exploited to compute
      the localized surface-plasmon resonance wavelength shift with respect to the bare
      metal from first principles.

PMID- 20151726
TI  - Cost effectiveness of high-dose intravenous esomeprazole for peptic ulcer
      bleeding.
AB  - Peptic ulcer bleeding (PUB) is a serious and sometimes fatal condition. The
      outcome of PUB strongly depends on the risk of rebleeding. A recent multinational
      placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT00251979)
      showed that high-dose intravenous (IV) esomeprazole, when administered after
      successful endoscopic haemostasis in patients with PUB, is effective in
      preventing rebleeding. From a policy perspective it is important to assess the
      cost efficacy of this benefit so as to enable clinicians and payers to make an
      informed decision regarding the management of PUB. Using a decision-tree model,
      we compared the cost efficacy of high-dose IV esomeprazole versus an approach of
      no-IV proton pump inhibitor for prevention of rebleeding in patients with PUB.
      The model adopted a 30-day time horizon and the perspective of third-party payers
      in the USA and Europe. The main efficacy variable was the number of averted
      rebleedings. Healthcare resource utilization costs (physician fees,
      hospitalizations, surgeries, pharmacotherapies) relevant for the management of
      PUB were also determined. Data for unit costs (prices) were primarily taken from
      official governmental sources, and data for other model assumptions were
      retrieved from the original clinical trial and the literature. After successful
      endoscopic haemostasis, patients received either high-dose IV esomeprazole (80 mg
      infusion over 30 min, then 8 mg/hour for 71.5 hours) or no-IV esomeprazole
      treatment, with both groups receiving oral esomeprazole 40 mg once daily from
      days 4 to 30. Rebleed rates at 30 days were 7.7% and 13.6%, respectively, for the
      high-dose IV esomeprazole and no-IV esomeprazole treatment groups (equating to a
      number needed to treat of 17 in order to prevent one additional patient from
      rebleeding). In the US setting, the average cost per patient for the high-dose IV
      esomeprazole strategy was $US14 290 compared with $US14 239 for the no-IV
      esomeprazole strategy (year 2007 values). For the European setting, Sweden and
      Spain were used as examples. In the Swedish setting the corresponding respective
      figures were Swedish kronor (SEK)67 862 ($US9220 at average 2006 interbank
      exchange rates) and SEK67 807 ($US9212) [year 2006 values]. Incremental cost
      effectiveness ratios were $US866 and SEK938 ($US127), respectively, per averted
      rebleed when using IV esomeprazole. For the Spanish setting, the high-dose IV
      esomeprazole strategy was dominant (more effective and less costly than the no-IV
      esomeprazole strategy) [year 2008 values]. All results appeared robust to
      univariate/threshold sensitivity analysis, with high-dose IV esomeprazole
      becoming dominant with small variations in assumptions in the US and Swedish
      settings, while remaining a dominant approach in the Spanish scenario across a
      broad range of values. Sensitivity variables with prespecified ranges included
      lengths of stay and per diem assumptions, rebleeding rates and, in some cases,
      professional fees. In patients with PUB, high-dose IV esomeprazole after
      successful endoscopic haemostasis appears to improve outcomes at a modest
      increase in costs relative to a no-IV esomeprazole strategy from the US and
      Swedish third-party payer perspective. Whereas, in the Spanish setting, the high
      dose IV esomeprazole strategy appeared dominant, being more effective and less
      costly.

PMID- 20151727
TI  - AQUASOL: An efficient solver for the dipolar Poisson-Boltzmann-Langevin equation.
AB  - The Poisson-Boltzmann (PB) formalism is among the most popular approaches to
      modeling the solvation of molecules. It assumes a continuum model for water,
      leading to a dielectric permittivity that only depends on position in space. In
      contrast, the dipolar Poisson-Boltzmann-Langevin (DPBL) formalism represents the
      solvent as a collection of orientable dipoles with nonuniform concentration; this
      leads to a nonlinear permittivity function that depends both on the position and
      on the local electric field at that position. The differences in the assumptions
      underlying these two models lead to significant differences in the equations they
      generate. The PB equation is a second order, elliptic, nonlinear partial
      differential equation (PDE). Its response coefficients correspond to the
      dielectric permittivity and are therefore constant within each subdomain of the
      system considered (i.e., inside and outside of the molecules considered). While
      the DPBL equation is also a second order, elliptic, nonlinear PDE, its response
      coefficients are nonlinear functions of the electrostatic potential. Many solvers
      have been developed for the PB equation; to our knowledge, none of these can be
      directly applied to the DPBL equation. The methods they use may adapt to the
      difference; their implementations however are PBE specific. We adapted the PBE
      solver originally developed by Holst and Saied [J. Comput. Chem. 16, 337 (1995)]
      to the problem of solving the DPBL equation. This solver uses a truncated Newton
      method with a multigrid preconditioner. Numerical evidences suggest that it
      converges for the DPBL equation and that the convergence is superlinear. It is
      found however to be slow and greedy in memory requirement for problems commonly
      encountered in computational biology and computational chemistry. To circumvent
      these problems, we propose two variants, a quasi-Newton solver based on a
      simplified, inexact Jacobian and an iterative self-consistent solver that is
      based directly on the PBE solver. While both methods are not guaranteed to
      converge, numerical evidences suggest that they do and that their convergence is
      also superlinear. Both variants are significantly faster than the solver based on
      the exact Jacobian, with a much smaller memory footprint. All three methods have
      been implemented in a new code named AQUASOL, which is freely available.

PMID- 20151729
TI  - Statistical model for small clusters transforming from one isomer to another.
AB  - Based on the fact that the kinetic energy of one atom in small cluster still
      obeys the Boltzmann distribution, a statistical model is developed to predict the
      time consumed by a small cluster transforming from one isomer to another and is
      tested by vast molecular dynamics simulations of C(12) isomers transformation in
      helium gas at high temperatures (2000-3500 K). Extrapolating the model to lower
      temperatures, we found that the time for the most probable isomer of C(12) formed
      at 2500 K turning into the most stable one is more than 10(12) years at room
      temperature.

PMID- 20151730
TI  - Assessment of an analytical density matrix derived from a modified Colle-Salvetti
      approach to the electron gas.
AB  - The Ragot-Cortona model of local correlation energy [S. Ragot and P. Cortona, J.
      Chem. Phys. 121, 7671 (2004)] revisits the initial approach of Colle and Salvetti
      [Theor. Chim. Acta 37, 329 (1975)] in order to reinstate the kinetic contribution
      T(c) to the total correlation energy E(c). In this work, the one-electron reduced
      density matrix underlying the amended model is fully derived in closed form. By
      construction, the said density matrix is parameter-free but not N-representable,
      owing to approximations used in the Ragot-Cortona approach. However, the
      resulting density matrix is shown to have formally correct short- and long-range
      expansions. Furthermore, its momentum-space counterpart qualitatively agrees with
      known parametrized momentum distributions except at small momenta, where the
      disagreement reflects the nonrepresentability of the model and restricts to a
      small fraction of the slowest electrons only.

PMID- 20151731
TI  - A Chebychev propagator with iterative time ordering for explicitly time-dependent
      Hamiltonians.
AB  - A propagation method for time-dependent Schrodinger equations with an explicitly
      time-dependent Hamiltonian is developed where time ordering is achieved
      iteratively. The explicit time dependence of the time-dependent Schrodinger
      equation is rewritten as an inhomogeneous term. At each step of the iteration,
      the resulting inhomogeneous Schrodinger equation is solved with the Chebychev
      propagation scheme presented in the work of M. Ndong et al. [J. Chem. Phys. 130,
      124108 (2009)]. The iteratively time-ordering Chebychev propagator is shown to be
      robust, efficient, and accurate and compares very favorably with all other
      available propagation schemes.

PMID- 20151732
TI  - Protein solvation from theory and simulation: Exact treatment of Coulomb
      interactions in three-dimensional theories.
AB  - Solvation forces dominate protein structure and dynamics. Integral equation
      theories allow a rapid and accurate evaluation of the effect of solvent around a
      complex solute, without the sampling issues associated with simulations of
      explicit solvent molecules. Advances in integral equation theories make it
      possible to calculate the angle dependent average solvent structure around an
      irregular molecular solution. We consider two methodological problems here: the
      treatment of long-ranged forces without the use of artificial periodicity or
      truncations and the effect of closures. We derive a method for calculating the
      long-ranged Coulomb interaction contributions to three-dimensional distribution
      functions involving only a rewriting of the system of integral equations and
      introducing no new formal approximations. We show the comparison of the exact
      forms with those implied by the supercell method. The supercell method is shown
      to be a good approximation for neutral solutes whereas the new method does not
      exhibit the known problems of the supercell method for charged solutes. Our
      method appears more numerically stable with respect to thermodynamic starting
      state. We also compare closures including the Kovalenko-Hirata closure, the
      hypernetted-chain (HNC) and an approximate three-dimensional bridge function
      combined with the HNC closure. Comparisons to molecular dynamics results are made
      for water as well as for the protein solute bovine pancreatic trypsin inhibitor.
      The proposed equations have less severe approximations and often provide results
      which compare favorably to molecular dynamics simulation where other methods
      fail.

PMID- 20151733
TI  - Alcohol solubility in a lipid bilayer: Efficient grand-canonical simulation of an
      interfacially active molecule.
AB  - We derive a new density-biased Monte Carlo technique which preserves detailed
      balance and improves the convergence of grand-canonical simulations of a species
      with a strong preference for an interfacial region as compared to the bulk. This
      density-biasing technique is applied to the solubility of "alcohol" molecules in
      a mesoscopic model of the lipid bilayer, a system which has anesthetic
      implications but is poorly understood.

PMID- 20151734
TI  - Genetic algorithm optimization of laser pulses for molecular quantum state
      excitation.
AB  - Conventionally optimal control theory has been used in the theoretical design of
      laser pulses through the direct variation in the electric field of the laser
      pulse as a function of time. This often leads to designed laser pulses which
      contain a broad and seemingly arbitrary frequency structure that varies in time
      in a manner which may be difficult to realize experimentally. In contrast, the
      experimental design of laser pulses has used a genetic algorithm (GA) approach,
      varying only those laser parameters actually available to the experimentalist. We
      investigate in this paper the possibility of using GA optimization methods in the
      theoretical design of laser pulses to bring about quantum state transitions in
      molecules. This allows us to select only a small limited number of parameters to
      vary and to choose these parameters so that they correspond to those available to
      the experimentalist. In the paper we apply our methods to the vibrational
      rotational excitation of the HF molecule. We choose a small limited number of
      frequencies and vary only the associated electric field amplitudes and pulse
      envelopes. We show that laser pulses designed in this way can lead to very high
      transition probabilities.

PMID- 20151735
TI  - Quantitative prediction of gas-phase (15)N and (31)P nuclear magnetic shielding
      constants.
AB  - High-level ab initio benchmark calculations of the (15)N and (31)P NMR chemical
      shielding constants for a representative set of molecules are presented. The
      computations have been carried out at the Hartree-Fock self-consistent field (HF
      SCF), density functional theory (DFT) (B-P86 and B3-LYP), second-order Moller
      Plesset perturbation theory (MP2), coupled cluster singles and doubles (CCSD),
      and CCSD augmented by a perturbative treatment of triple excitations [CCSD(T)]
      level of theory using basis sets of triple zeta quality or better. The influence
      of the geometry, the treatment of electron correlation, as well as basis set and
      zero-point vibrational effects on the shielding constants are discussed and the
      results are compared to gas-phase experimental shifts. As for the first time a
      study using high-level post-HF methods is carried out for a second-row element,
      we also propose a family of basis sets suitable for the computation of (31)P
      shielding constants. The mean deviations observed for (15)N and (31)P are 0.9
      [CCSD(T)/13s9p4d3f] and -3.3 ppm [CCSD(T)/15s12p4d3f2g], respectively, when
      corrected for zero-point vibrational effects. Results obtained at the DFT level
      of theory are of comparable accuracy to MP2 for (15)N and of comparable accuracy
      to HF-SCF for (31)P. However, they are not improved by inclusion of zero-point
      vibrational effects. The PN molecule is an especially interesting case with
      exceptionally large electron correlation effects on shielding constants beyond
      MP2 which, therefore, represents an excellent example for further benchmark
      studies.

PMID- 20151736
TI  - Analytical theory of finite-size effects in mechanical desorption of a polymer
      chain.
AB  - We discuss a unique system that allows exact analytical investigation of first-
      and second-order transitions with finite-size effects: mechanical desorption of
      an ideal lattice polymer chain grafted with one end to a solid substrate with a
      pulling force applied to the other end. We exploit the analogy with a continuum
      model and use accurate mapping between the parameters in continuum and lattice
      descriptions, which leads to a fully analytical partition function as a function
      of chain length, temperature (or adsorption strength), and pulling force. The
      adsorption-desorption phase diagram, which gives the critical force as a function
      of temperature, is nonmonotonic and gives rise to re-entrance. We analyze the
      chain length dependence of several chain properties (bound fraction, chain
      extension, and heat capacity) for different cross sections of the phase diagram.
      Close to the transition a single parameter (the product of the chain length N and
      the deviation from the transition point) describes all thermodynamic properties.
      We discuss finite-size effects at the second-order transition (adsorption without
      force) and at the first-order transition (mechanical desorption). The first-order
      transition has some unusual features: The heat capacity in the transition region
      increases anomalously with temperature as a power law, metastable states are
      completely absent, and instead of a bimodal distribution there is a flat region
      that becomes more pronounced with increasing chain length. The reason for this
      anomaly is the absence of an excess surface energy for the boundary between
      adsorbed and stretched coexisting phases (this boundary is one segment only): The
      two states strongly fluctuate in the transition point. The relation between
      mechanical desorption and mechanical unzipping of DNA is discussed.

PMID- 20151737
TI  - Theoretical study for the reaction of CH(3)CN with O((3)P).
AB  - The low-lying triplet and singlet potential energy surfaces of the
      O((3)P)+CH(3)CN reaction have been studied at the G3(MP2)//B3LYP/6-311+G(d,p)
      level. On the triplet surface, six kinds of pathways are revealed, namely, direct
      hydrogen abstraction, C-addition/elimination, N-addition/elimination,
      substitution, insertion, and H-migration. Multichannel Rice-Ramsperger-Kassel
      Marcus theory and transition-state theory are employed to calculate the overall
      and individual rate constants over a wide range of temperatures and pressures. It
      is predicted that the direct hydrogen abstraction and C-addition/elimination on
      triplet potential energy surface are dominant pathways. Major predicted end
      products include CH(3)+NCO and CH(2)CN+OH. At atmospheric pressure with Ar and
      N(2) as bath gases, CH(3)C(O)N (IM1) formed by collisional stabilization is
      dominated at T<700 K, whereas CH(3) and NCO produced by C-addition/elimination
      pathway are the major products at the temperatures between 800 and 1500 K; the
      direct hydrogen abstraction leading to CH(2)CN+OH plays an important role at
      higher temperatures in hydrocarbon combustion chemistry and flames, with
      estimated contribution of 64% at 2000 K. Furthermore, the calculated rate
      constants are in good agreement with available experimental data over the
      temperature range 300-600 K. The kinetic isotope effect has also been calculated
      for the triplet O((3)P)+CH(3)CN reaction. On the singlet surface, the atomic
      oxygen can easily insert into C-H or C-C bonds of CH(3)CN, forming the insertion
      intermediates s-IM8(HOCH(2)CN) and s-IM5(CH(3)OCN) or add to the carbon atom of
      CN group in CH(3)CN, forming the addition intermediate s-IM1(CH(3)C(O)N); both
      approaches were found to be barrierless. It is indicated that the singlet
      reaction exhibits a marked difference from the triplet reaction. This calculation
      is useful to simulate experimental investigations of the O((3)P)+CH(3)CN reaction
      in the singlet state surface.

PMID- 20151738
TI  - Disparate product distributions observed in Mo((3-x))W(x)O(y) (-) (x=0-3; y=3-9)
      reactions with D(2)O and CO(2).
AB  - Results of gas phase reactivity studies on group six transition metal suboxide
      clusters, Mo(3)O(y) (-), Mo(2)WO(y) (-), MoW(2)O(y) (-), and W(3)O(y) (-) (Mo((3
      x))W(x)O(y) (-), x=0-3; y=ca. 3-9) with both D(2)O and CO(2) are reported.
      Sequential oxidation for the more reduced species, Mo((3-x))W(x)O(y) (
      )+D(2)O/CO(2)-->Mo((3-x))W(x)O(y+1) (-)+D(2)/CO, and dissociative addition for
      certain species, Mo((3-x))W(x)O(y) (-)+D(2)O/CO(2)-->Mo((3-x))W(x)O(y+1)D(2) (
      )/Mo((3-x))W(x)O(y+1)CO(-), is evident in the product distributions observed in
      mass spectrometric measurements. Reactions with D(2)O proceed at a rate that is
      on the order of 10(2) higher than for CO(2). The pattern of reaction products
      reveals composition-dependent chemical properties of these group six unary and
      binary clusters. At the core of this variation is the difference in Mo-O and W-O
      bond energies, the latter of which is significantly higher. This results in a
      larger thermodynamic drive to higher oxidation states in clusters with more
      tungsten atoms. However, addition products for more oxidized W-rich clusters are
      not observed, while they are observed for the more Mo-rich clusters. This is
      attributed to the following: In the higher oxides (e.g., y=8), addition reactions
      require distortion of local metal-oxygen bonding, and will necessarily have
      higher activation barriers for W-O bonds, since the vibrational potentials will
      be narrower. The binary (x=1,2) clusters generally show sequential oxidation to
      higher values of y. This again is attributed to higher W-O bond energy, the
      result being that stable binary structures have W atoms in higher oxidation
      states, and Mo centers both in more reduced states and sterically unhindered. The
      reduced Mo center provides a locus of higher reactivity. An unusual result that
      is not readily explained is the chemically inert behavior of Mo(3)O(6) (-).

PMID- 20151739
TI  - Cooperative and diminutive hydrogen bonding in Y...HCN...HCN and NCH...Y...HCN
      trimers (Y=BF,CO,N2).
AB  - A computational study of the cooperative effect of hydrogen bonding in
      Y...HCN...HCN and its diminutive effect in NCH...Y...HCN (Y=BF,CO,N2) linear
      complexes relative to the Y...HCN dimer was undertaken at the MP2/6-311++G(2d,2p)
      level of theory. It was found that the additional hydrogen bond in Y...HCN...HCN
      leads to an enhanced Y...HCN dissociation energy, extended H-C bond length, and
      larger redshift of the H-C stretch relative to Y...HCN, while opposite features
      are observed in NCH...Y...HCN. The cooperativity is diminished as the hardness of
      the Y atom directly bonded to the HCN molecule increases. A particularly
      interesting result is that the small bond contraction and blueshift associated
      with the H-C bond in BF...HCN is converted to a small bond extension and redshift
      on the formation of the BF...HCN...HCN trimer.

PMID- 20151740
TI  - Argon nucleation in a cryogenic supersonic nozzle.
AB  - We have measured pressures p and temperatures T corresponding to the maximum
      nucleation rate of argon in a cryogenic supersonic nozzle apparatus where the
      estimated nucleation rates are J=10(17+/-1) cm(-3) s(-1). As T increases from 34
      to 53 K, p increases from 0.47 to 8 kPa. Under these conditions, classical
      nucleation theory predicts nucleation rates of 11-13 orders of magnitude lower
      than the observed rates while mean field kinetic nucleation theory predicts the
      observed rates within 1 order of magnitude. The current data set appears
      consistent with the measurements of Iland et al. [J. Chem. Phys. 127, 154506
      (2007)] in the cryogenic nucleation pulse chamber. Combining the two data sets
      suggests that classical nucleation theory fails because it overestimates both the
      critical cluster size and the excess internal energy of the critical clusters.

PMID- 20151741
TI  - Exploring the mechanisms of H atom loss in simple azoles: Ultraviolet photolysis
      of pyrazole and triazole.
AB  - The photophysics of gas phase pyrazole (C(3)N(2)H(4)) and 2H-1,2,3-triazole
      (C(2)N(3)H(3)) molecules following excitation at wavelengths in the range 230
      nm>or=lambda(phot)>or=193.3 nm has been investigated using the experimental
      technique of H (Rydberg) atom photofragment translational spectroscopy. The
      findings are compared with previous studies of pyrrole (C(4)N(1)H(5)) and
      imidazole (C(3)N(2)H(4)), providing a guide to H atom loss dynamics in simple N
      containing heterocycles. CASPT2 theoretical methods have been employed to
      validate these findings. Photoexcitation of pyrazole at the longest wavelengths
      studied is deduced to involve pi( *)<--pi excitation, but photolysis at
      lambda(phot)</=214 nm is characterized by rapid N-H bond fission on a (1)pisigma(
      *) potential energy surface. The eventual pyrazolyl radical products are formed
      in a range of vibrational levels associated with both the ground ((2)A(2)) and
      first excited ((2)B(1)) electronic states as a result of nonadiabatic coupling at
      large N-H bond lengths. The excitation energy of the lowest (1)pisigma( *) state
      of pyrazole is found to be significantly higher in energy than that of pyrrole
      and imidazole. Similar studies of 2H-1,2,3-triazole reveal that the lowest
      (1)pisigma( *) state is yet higher in energy and not accessible following
      excitation at lambda(phot)>or=193.3 nm. The N-H bond strength of pyrazole is
      determined as 37 680+/-40 cm(-1), significantly greater than that of the N-H
      bonds in pyrrole and imidazole. The correlation between the photochemistry of
      azoles and the number and position of nitrogen atoms within the ring framework is
      discussed in terms of molecular symmetry and orbital electron density. A
      photodissociation channel yielding H atoms with low kinetic energies is also
      clearly evident in both pyrazole and 2H-1,2,3-triazole. Companion studies of
      pyrazole-d(1) suggest that these slow H atoms arise primarily from the N-H site,
      following pi( *)<--pi excitation, and subsequent internal conversion and/or
      unintended multiphoton absorption processes.

PMID- 20151742
TI  - Probing the structural evolution of Cu(N) (-), N=9-20, through a comparison of
      computed electron removal energies and experimental photoelectron spectra.
AB  - Computed electron removal energies for Cu(N) (-) clusters, N=9-20, are presented
      for the three lowest-energy isomers obtained from extensive, unbiased searches
      for the minimum energy structure at each size. The density functional theory
      (DFT) computations make use of a scheme introduced by Jellinek and Acioli (JA)
      [J. Chem. Phys. 118, 7783 (2003)] that obtains electron removal energies from DFT
      orbital energies using corrections based on DFT total energies. The computed
      removal energies are compared with the measured photoelectron spectra (PES) for
      Cu(N) (-). The patterns of computed removal energies are shown to be isomer
      specific for clusters in this size range. By matching the computed removal
      energies to the observed PES, the isomers responsible for the PES are identified.
      The results of the JA scheme are compared to those obtained using other DFT-based
      methods.

PMID- 20151743
TI  - Ab initio characterization of the Ca-HCl van der Waals complex.
AB  - The equilibrium structure and three-dimensional potential energy surface of the
      Ca-HCl van der Waals complex in its ground electronic state have been determined
      from accurate ab initio calculations using the coupled-cluster method, CCSD(T),
      in conjunction with basis sets of quadruple- and quintuple-zeta quality. The core
      electron correlation, high-order valence-electron correlation, and scalar
      relativistic effects were investigated. The Ca-HCl complex was confirmed to be
      linear at equilibrium, with the vibrationless dissociation energy (into Ca and
      HCl) D(e) of 287 cm(-1). The vibration-rotation energy levels of various Ca-HCl
      isotopomers were predicted using the variational method. The predicted
      spectroscopic constants can be useful in a further analysis of high-resolution
      vibration-rotation spectra of the Ca-HCl complex.

PMID- 20151744
TI  - The barrier height, unimolecular rate constant, and lifetime for the dissociation
      of HN(2).
AB  - Although never spectroscopically identified in the laboratory, hydrogenated
      nitrogen (HN(2)) is thought to be an important species in combustion chemistry.
      The classical barrier height (10.6+/-0.2 kcal mol(-1)) and exothermicity (3.6+/
      0.2 kcal mol(-1)) for the HN(2)-->N(2)+H reaction are predicted by high level ab
      initio quantum mechanical methods [up to CCSDT(Q)]. Total energies are
      extrapolated to the complete basis set limit applying the focal point analysis.
      Zero-point vibrational energies are computed using fundamental (anharmonic)
      frequencies obtained from a quartic force field. Relativistic and diagonal Born
      Oppenheimer corrections are also taken into account. The quantum mechanical
      barrier with these corrections is predicted to be 6.4+/-0.2 kcal mol(-1) and the
      reaction exothermicity to be 8.8+/-0.2 kcal mol(-1). The importance of these
      parameters for the thermal NO(x) decomposition (De-NO(x)) process is discussed.
      The unimolecular rate constant for dissociation of the HN(2) molecule and its
      lifetime are estimated by canonical transition-state theory and Rice-Ramsperger
      Kassel-Marcus theory. The lifetime of the HN(2) molecule is here estimated to be
      2.8x10(-10) s at room temperature. Our result is in marginal agreement with the
      latest experimental kinetic modeling studies (tau=1.5x10(-8) s), albeit
      consistent with the very rough experimental upper limit (tau<0.5 mus). For the
      dissociation reaction, kinetic isotope effects are investigated. Our analysis
      demonstrates that the DN(2) molecule has a longer lifetime than the HN(2)
      molecule. Thus, DN(2) might be more readily identified experimentally. The
      ionization potential of the HN(2) molecule is determined by analogous high level
      ab initio methods and focal point analysis. The adiabatic IP of HN(2) is
      predicted to be 8.19+/-0.05 eV, in only fair agreement with the experimental
      upper limit of 7.92 eV deduced from sychrothon-radiation-based photoionization
      mass spectrometry.

PMID- 20151745
TI  - Spectroscopic investigation of OCS (p-H(2))(n) (n=1-16) complexes inside helium
      droplets: Evidence for superfluid behavior.
AB  - Up to 16 parahydrogen and orthodeuterium molecules have been assembled around an
      OCS carbonyl sulfide chromophore molecule inside the pure (4)He and mixed
      (4)He(3)He droplets at temperatures of 0.38 and 0.15 K, respectively. The
      infrared spectra of the resulting complexes exhibit a sequence of rotationally
      resolved vibrational nu(3) bands in the vicinity of 2060 cm(-1), which are
      sufficiently separated to assign them to clusters with specific numbers of
      attached molecules for n=1-16. The present article contains the first complete
      analysis of the spectra for n=2-8 and a full documentation of the results for n=8
      15 briefly described in a short report [Europhys. Lett. 83, 66008 (2008)].
      Distinct rotational Q-branches are observed for all OCS-(o-D(2))(n) clusters at
      the He droplet temperatures of 0.38 K and 0.15 K, indicating that the (o-D(2))(n)
      shell rotates nearly freely about the molecular OCS axis. In the case of OCS-(p
      H(2))(n) at 0.38 K, the Q-branch is seen for most n, with the exception of n=5, 6
      and n=12. At 0.15 K, the Q-branch has disappeared for all n>or=11, indicating
      that the axial rotations are no longer active. Previously, the absence of a Q
      branch for n=5 and 6 was explained by the high group symmetry of the bosonic p
      H(2) rigid (donut) rings around the OCS molecule. This model, however, fails in
      explaining the disappearance of the Q-branch for n>or=11. In essential agreement
      with recent path-integral Monte Carlo calculations, the observed phenomenon is
      attributed to the onset of superfluidity in the multiring p-H(2) shell and the
      related permutations of bosonic p-H(2) molecules. A floppy shell model, which
      accounts for the effect of tunneling and exchange of molecules within the
      clusters, is able to explain the postulated superfluid behavior of the p-H(2)
      shell at low temperatures. Within this model the activation of states of low
      axial symmetry is responsible for the appearance of the Q-branch at higher
      temperatures.

PMID- 20151746
TI  - Quantum instanton evaluations of surface diffusion, interior migration, and
      surface-subsurface transport for H/Ni.
AB  - The quantum instanton approximation is extended to investigate dynamical
      processes of hydrogen on surface, from surface to subsurface, and between
      interior sites in nickel lattice. The path integral Monte Carlo and adaptive
      umbrella sampling techniques are employed to manipulate the quantum instanton
      formula. The free energy profiles along reaction paths, temperature dependence of
      free energies, and rates as well as diffusion coefficients are calculated for
      each process. The results manifest that the motions of nickel atoms beneath the
      surface have little effect on the hydrogen diffusion on Ni(111), and the hydrogen
      at the fcc binding site is much easier to get into bulk nickel than the one at
      the hcp site. The temperature dependence of free energy profiles also reveals
      that the hydrogen in the subsurface octahedral vacancy and interior tetrahedral
      vacancy becomes unstable at low temperatures, which proposes a temperature
      dependence of reaction mechanism. In addition, the relaxations of the lattices
      dramatically lower the free energy barriers except for the process of the
      hydrogen diffusion on Ni(111). The quantum motions of the lattice atoms affect
      the free energies little at 300 K, but they hinder the rates by 20%-40% compared
      with the classical motions of lattice atoms.

PMID- 20151747
TI  - A comparative ab initio study of neutral and charged kink solitons on conjugated
      carbon chains.
AB  - The ground state of odd-N polyynic oligomers C(N)H(2) features kink solitons in
      carbon-carbon bond-length alternation (BLA) patterns. We perform a systematic
      first-principles computational study of neutral and singly charged kinks in long
      oligomers addressing relationships between BLA patterns, electron energy gaps,
      and accompanying distributions of spin and charge densities, both in vacuum and
      in the screening solvent environment. A quantitative comparison is made of the
      results derived with four different ab initio methods: from pure density
      functional theory to pure Hartree-Fock (HF) and including two popular hybrid
      density functionals, B3LYP and BHandHLYP. A clear correlation is demonstrated
      between the derived spatial extent of kinks and the amount of HF exchange used in
      the functionals. For charged kinks, we find a substantial difference in the
      behavior of charge and spin densities.

PMID- 20151748
TI  - Thermodynamic stability of soft-core Lennard-Jones fluids and their mixtures.
AB  - Thermodynamic stability of model single component and binary mixture fluids is
      considered with the Fisher-Ruelle (FR) stability criteria, which apply in the
      thermodynamic limit, and molecular dynamics (MD) simulation for finite periodic
      systems. Two soft-core potential forms are considered,
      phi(6,1)(r)=4[1/(a+r(6))(2)-1/(a+r(6))] and phi(2,3)(r)=4[1/(a+r(2))(6)
      1/(a+r(2))(3)], where r is the separation between the particle centers. According
      to FR these are unstable in the thermodynamic limit if a>a(c)=1/2 and
      a>a(c)=(7/32)(1/3), respectively. MD simulations with single-component particles
      show, however, that this transition on typical simulation times is more gradual
      for finite periodic systems with variation in a on either side of a(c). For
      a<a(c), asymmetric density fluctuations are stabilized by the periodic boundary
      conditions. Also for binary mixtures of (stable) Lennard-Jones and phi(2,3)
      particles, phase separation into regions richer in one component than the other
      was observed for a<a(c). Binary systems with interactions similar to a model
      polymer-colloid fluid in the "depletion" limit equilibrated particularly slowly
      for a>a(c), with the unstable component in the mixture breaking up into many long
      lived microdroplets which conferred apparent equilibrium thermodynamic behavior
      (i.e., negligible N-dependence of the average potential energy per particle) in
      this period.

PMID- 20151749
TI  - Dynamics of water at the nanoscale hydrophobic confinement.
AB  - We investigate the effect of solute surface topology created by considering
      various intermolecular separations of the hydrophobic, paraffinlike plates on the
      dynamics of water confined between two such plates. The solute plates are made up
      of 5 n-C(18)H(38) molecules arranged in parallel in such a way that all the
      carbon atoms of the paraffin molecule are lying on the same plane. Results are
      obtained from extensive molecular dynamics simulations of aqueous solutions of
      paraffinlike plates in the isothermal-isobaric ensemble. A strong dependence of
      the translational as well as vibrational dynamics of the confined water molecules
      on surface topology (intermolecular distance within the paraffinlike plate) has
      been observed. Analysis of mean squared displacement reveals anomalous nonlinear
      behavior of the water molecules in the nanoconfined environment.

PMID- 20151750
TI  - Confinement of Ar between two identical parallel semi-infinite walls.
AB  - The confinement of Ar in planar slits of two identical parallel semi-infinite
      walls of alkali metals, alkaline-earth metal Mg, and CO(2) is investigated within
      the framework of the density functional theory. It is assumed that (1) the fluid
      atoms interact via a recently proposed effective attractive pair potential with
      strength, epsilon(ff), which reproduces the experimental data of the surface
      tension of the liquid-vapor interface at the bulk coexistence curve, and (2) the
      adsorption on the walls is described by ab initio potentials characterized by a
      well depth, W(sf). In this way the systems were studied in the framework of a
      realistic approach. We found that for small coverages, the slit is always filled
      by forming two symmetric vapor films, one at each wall. For increasing coverage
      the behavior depends on the ratio W(sf)/epsilon(ff) and the temperature T. In the
      case of alkali metals, we found at the triple point, T(t), of the adsorbate a
      regime of average density rho(av) ( *) in which the ground state exhibits
      asymmetric density profiles, leading to the so-called spontaneous symmetry
      breaking (SSB) effect. The SSB appears at an average density rho(sb1) ( *) and
      disappears at a higher average density rho(sb2) ( *). When T is increased, the
      range of densities rho(sb1) ( *)<or=rho(av) ( *)<or=rho(sb2) ( *) diminishes and
      eventually the SSB disappears at a critical temperature, T(sb), which coincides
      with the critical prewetting temperature T(cpw) observed in the adsorption on a
      single wall. For T>T(cpw) the slit is filled symmetrically up to the phase
      transition to capillary condensation. All these features are examined as a
      function of the strength of the substrate and the width of the slit. Furthermore,
      no SSB effect was found for Mg and CO(2).

PMID- 20151751
TI  - Thioglycolic acid on the gold (111) surface and Raman vibrational spectra.
AB  - The interaction of thioglycolic acid (HSCH(2)COOH) with the Au(111) surface is
      investigated, and it is found that at the low coverage the molecule lies down on
      the substrate. If the mercaptan-hydrogen atom is eliminated, the resulting
      SCH(2)COOH molecule is randomly oriented on the surface. If the carboxylic acid
      group in the HSCH(2)COOH molecule is deprotonated instead, the HSCH(2)COO(-)
      molecule lies down on the surface. However, when the mercaptan-hydrogen atom in
      the HSCH(2)COO(-) molecule is removed, the resulting SCH(2)COO(-) molecule rises
      up to a certain level on the substrate. The calculated Raman vibrational spectra
      decipher which compounds and atomic displacements contribute to the corresponding
      frequencies. We thus propose a consistent mechanism for the deposition of
      thioglycolic acid on the Au(111) surface.

PMID- 20151752
TI  - Density functional theory study of the optical and electronic properties of
      oligomers based on phenyl-ethynyl units linked to triazole, thiadiazole, and
      oxadiazole rings to be used in molecular electronics.
AB  - In the present work, we have studied from a theoretical perspective the geometry
      and electronic properties of the series of related compounds 2,5
      bis(phenylethynyl)-1,3,4-thiadiazole, 2,5-bis(phenylethynyl)-1,3,4-oxadiazole,
      and 2,5-bis(phenylethynyl)-1,2,4-triazole as candidates for electron-conducting
      polymers and compounds with desirable (opto)electronic properties. The effect of
      the ethynyl group (-C[Triple Bond]C-) on the structure and electronic properties
      was also studied. The influence of planarity on electrical conductivity has been
      studied by a natural-bond-orbital analysis. The (opto)electronic properties and
      conducting capability were investigated through the highest occupied molecular
      orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap, excitation energy,
      bond length alternation, LUMO energy, electron affinities, and intramolecular
      reorganization energy. Finally, the evolution of some properties such as optical
      bandgap and electron affinity with the increase of the number of repeat units in
      the oligomer chain has been checked.

PMID- 20151753
TI  - Negative salt effect in an acid-base diode: Simulations and experiments.
AB  - The paper describes a new phenomenon discovered in the electrolytic analog of a
      semiconductor diode. As an example, the phenomenon is studied in the 0.1M KOH
      0.1M HCl diode where the alkaline and the acidic reservoirs are connected by a
      hydrogel cylinder. First the traditional, so-called positive salt effect is
      discussed. In that case some salt is added to the alkaline reservoir of a reverse
      biased electrolyte diode and as a result, close to a critical concentration of
      the added salt the electric current increases sharply. The so-called negative
      salt effect appears as a suppression of the positive one. It is shown by
      numerical simulations, by approximate analytical formulae, and also by
      experiments that the high current caused by the salt contamination in the
      alkaline reservoir can be mostly suppressed by relatively small salt
      concentrations in the acidic reservoir. Thus a straightforward application of the
      negative salt effect would be the sensitive detection of nonhydrogen cations in
      an acidic medium (e.g., in ion chromatography).

PMID- 20151754
TI  - External potential dynamic studies on the formation of interface in polydisperse
      polymer blends.
AB  - The formation of interface from an initial sharp interface in polydisperse A/B
      blends is studied using the external potential dynamic method. The present model
      is a nonlocal coupling model as we take into account the correlation between
      segments in a single chain. The correlation is approximately expressed by Debye
      function and the diffusion dynamics are based on the Rouse chain model. The chain
      length distribution is described by the continuous Schulz distribution. Our
      numerical calculation indicates that for a wide range of the Flory-Huggins
      parameter the broadening of interface with respect to time obeys a power law at
      early time, and the power indices are the same for both monodisperse and
      polydisperse blends. The power index is larger than that in the local coupling
      model. However, there is no unified scaling form of the broadening of the
      interface width if only the interfacial width at equilibrium is taken into
      account as the characteristic length of the system, because the correlation makes
      an extra characteristic length in the system, and the polydispersity is related
      to this length.

PMID- 20151755
TI  - A numerical study of mobility in thin films of fullerene derivatives.
AB  - The effect of functional group size on the electron mobility in films of
      fullerene derivatives is investigated numerically. A series of four C(60)
      derivatives are formed by attaching saturated hydrocarbon chains to the C(60)
      cage via a methano bridge. For each of the derivatives investigated, molecular
      dynamics is used to generate a realistic material morphology. Quantum chemical
      methods are then used to calculate intermolecular charge transfer rates. Finally,
      Monte Carlo methods are used to simulate time-of-flight experiments and thus
      calculate the electron mobility. It is found that as the length of the aliphatic
      side chain increases, the configurational disorder increases and thus the
      mobility decreases.

PMID- 20151756
TI  - Interplay between micelle formation and waterlike phase transitions.
AB  - A lattice model for amphiphilic aggregation in the presence of a structured
      waterlike solvent is studied through Monte Carlo simulations. We investigate the
      interplay between the micelle formation and the solvent phase transition in two
      different regions of temperature-density phase diagram of pure water. A second
      order phase transition between the gaseous (G) and high density liquid (HDL)
      phases that occurs at very high temperatures, and a first order phase transition
      between the low density liquid (LDL) and (HDL) phases that takes place at lower
      temperatures. In both cases, we find the aggregate size distribution curve and
      the critical micellar concentration as a function of the solvent density across
      the transitions. We show that micelle formation drives the LDL-HDL first order
      phase transition to lower solvent densities, while the transition G-HDL is driven
      to higher densities, which can be explained by the markedly different degrees of
      micellization in both cases. The diffusion coefficient of surfactants was also
      calculated in the LDL and HDL phases, changing abruptly its behavior due to the
      restructuring of waterlike solvent when we cross the first order LDL-HDL phase
      transition. To understand such behavior, we calculate the solvent density and the
      number of hydrogen bonds per water molecule close to micelles. The curves of the
      interfacial solvent density and the number of hydrogen bonds per water molecule
      in the first hydration signal a local phase change of the interfacial water,
      clarifying the diffusion mechanism of free surfactants in the solvent.

PMID- 20151757
TI  - Parallel tempering Monte Carlo simulations of lysozyme orientation on charged
      surfaces.
AB  - In this work, the parallel tempering Monte Carlo (PTMC) algorithm is applied to
      accurately and efficiently identify the global-minimum-energy orientation of a
      protein adsorbed on a surface in a single simulation. When applying the PTMC
      method to simulate lysozyme orientation on charged surfaces, it is found that
      lysozyme could easily be adsorbed on negatively charged surfaces with "side-on"
      and "back-on" orientations. When driven by dominant electrostatic interactions,
      lysozyme tends to be adsorbed on negatively charged surfaces with the side-on
      orientation for which the active site of lysozyme faces sideways. The side-on
      orientation agrees well with the experimental results where the adsorbed
      orientation of lysozyme is determined by electrostatic interactions. As the
      contribution from van der Waals interactions gradually dominates, the back-on
      orientation becomes the preferred one. For this orientation, the active site of
      lysozyme faces outward, which conforms to the experimental results where the
      orientation of adsorbed lysozyme is co-determined by electrostatic interactions
      and van der Waals interactions. It is also found that despite of its net positive
      charge, lysozyme could be adsorbed on positively charged surfaces with both "end
      on" and back-on orientations owing to the nonuniform charge distribution over
      lysozyme surface and the screening effect from ions in solution. The PTMC
      simulation method provides a way to determine the preferred orientation of
      proteins on surfaces for biosensor and biomaterial applications.

PMID- 20151758
TI  - Polypeptides in alpha-helix conformation perform as diodes.
AB  - Molecules that resemble a semiconductor diode depletion zone are those with an
      intrinsic electric dipole, which were suggested as potential electronic devices.
      However, so far, no single molecule has met such a goal because any electron
      donor-acceptor linker strongly diminishes any possibility of diode behavior. We
      find an intrinsic diode behavior in polypeptides such as poly(L-alanine) and
      polyglycine in alpha-helix conformation, explained in terms of molecular orbital
      theory using ab initio methods. The application of an antiparallel electric field
      with respect to the molecular dipole yields a gradual increase in current through
      the junction because the valence and conduction orbitals approach each other
      reducing their gap as the bias increases. However, a parallel field makes the gap
      energy increase, avoiding the pass of the electrons.

PMID- 20151759
TI  - Sequence dependent self-assembly of beta-peptides: Insights from a coarse-grained
      model.
AB  - The sequence-directed self-assembly of amphiphilic beta-peptides is studied using
      Monte Carlo simulations. A phenomenological model is employed where each molecule
      is modeled as a rigid nanorod with side groups located at positions to mimic
      globally amphiphilic (GA) and nonglobally amphiphilic (non-GA) isomers of beta
      peptides. The strength and the range of interactions between side groups are
      chosen based on the types of residues. The simulations show that the aggregation
      of beta-peptides is sensitive to the sequence and the residue types. For one type
      of beta-peptide the GA isomer has a greater tendency to aggregate while for the
      other the non-GA isomer has a greater tendency to aggregate. The trends observed
      in the simulations are consistent with recent experiments [Pomerantz et al., J.
      Am. Chem. Soc. 128, 8730 (2006); Pomerantz et al., Angew. Chem., Int. Ed. 47, 1
      (2008)], although the molecules do not spontaneously form the hollow fibers seen
      in experiment. Simulations with initial configurations as hollow fibers show that
      the stability of the fibers follows the same trend as the tendency for
      aggregation. The simulations demonstrate that the details matter: the self
      assembly of the molecules is sensitive to the strength of the short-ranged
      interactions and the size of the side groups, in addition to the global
      amphiphilicity of the molecules. This suggests the possibility of designing
      molecules for desired nanostructures.

PMID- 20151761
TI  - Effects of side-chain packing on the formation of secondary structures in protein
      folding.
AB  - We have recently shown that protein folding is driven by the water-entropy gain.
      When the alpha-helix or beta-sheet is formed, the excluded volumes generated by
      the backbone and side chains overlap, leading to an increase in the total volume
      available to the translational displacement of water molecules. Primarily by this
      effect, the water entropy becomes higher. At the same time, the dehydration
      penalty (i.e., the break of hydrogen bonds with water molecules) is compensated
      by the formation of intramolecular hydrogen bonds. Hence, these secondary
      structures are very advantageous units, which are to be formed as much as
      possible in protein folding. The packing of side chains, which leads to a large
      increase in the water entropy, is also crucially important. Here we investigate
      the roles of the side-chain packing in the second structural preference in
      protein folding. For some proteins we calculate the hydration entropies of a
      number of structures including the native structure with or without side chains.
      A hybrid of the angle-dependent integral equation theory combined with the
      multipolar water model and the morphometric approach is employed in the
      calculation. Our major findings are as follows. For the structures without side
      chains, there is an apparent tendency that the water entropy becomes higher as
      the alpha-helix or beta-sheet content increases. For the structures with side
      chains, however, a higher content of alpha-helices or beta-sheets does not
      necessarily lead to larger entropy of water due to the effect of the side-chain
      packing. The thorough, overall packing of side chains, which gives little space
      in the interior, is unique to the native structure. To accomplish such specific
      packing, the alpha-helix and beta-sheet contents are prudently adjusted in
      protein folding.

PMID- 20151760
TI  - Lateral organization of complex lipid mixtures from multiscale modeling.
AB  - The organizational properties of complex lipid mixtures can give rise to
      functionally important structures in cell membranes. In model membranes, ternary
      lipid-cholesterol (CHOL) mixtures are often used as representative systems to
      investigate the formation and stabilization of localized structural domains
      ("rafts"). In this work, we describe a self-consistent mean-field model that
      builds on molecular dynamics simulations to incorporate multiple lipid components
      and to investigate the lateral organization of such mixtures. The model
      predictions reveal regions of bimodal order on ternary plots that are in good
      agreement with experiment. Specifically, we have applied the model to ternary
      mixtures composed of dioleoylphosphatidylcholine:18:0 sphingomyelin:CHOL. This
      work provides insight into the specific intermolecular interactions that drive
      the formation of localized domains in these mixtures. The model makes use of
      molecular dynamics simulations to extract interaction parameters and to provide
      chain configuration order parameter libraries.

PMID- 20151762
TI  - Changes of metabolic profile in men treated for androgenetic alopecia with 1 mg
      finasteride.
AB  - OBJECTIVE: Androgenetic alopecia is recognized as a risk factor for
      cardiovascular diseases, glucose metabolism disorders, and benign prostate
      hyperplasia and/or carcinoma. Finasteride, used for treatment of androgenetic
      alopecia at a dose of 1mg/day, is an effective inhibitor of type II 5alpha
      reductase, the enzyme responsible for the reduction of testosterone to
      dihydrotestosterone. Recent studies reported that dihydrotestosterone, among
      other activities, might play some role in visceral fat metabolism. It thus seemed
      reasonable to examine whether finasteride treatment of androgenetic alopecia
      ameliorates some features of metabolic syndrome frequently seen associated with
      this condition. METHODS: We examined 12 men with premature balding (defined as
      frontoparietal and vertex hair loss before age 30 with alopecia defined as grade
      3 vertex or more on the Norwood-modified Hamilton alopecia classification).
      Hormonal levels and metabolic parameters were determined and insulin tolerance
      tests performed for all individuals. Finasteride (1 mg/day) was administrated for
      12 months. The hormonal profile and lipid spectrum were monitored after 4, 8 and
      12 months of treatment and insulin tolerance tests were repeated after 12 months
      of the treatment. RESULTS: After treatment with finasteride the expected changes
      in the steroid spectrum were seen, namely a decrease in dihydrotestosterone and
      increase in testosterone, androstenedione and free testosterone index. We
      observed an initial increase in total cholesterol and HDL- and LDL-cholesterol,
      which stabilized with prolonged treatment. We founded a significant decrease in
      glycated hemoglobin HbA1c and insulin resistance measured using rate constant for
      plasma glucose disappearance (kITT) showed only a borderline decrease.
      CONCLUSIONS: Finasteride is an efficient 5alpha-reductase inhibitor even at low
      doses of 1 mg/day. In men treated with this dose for 12 months, we observed mild
      differences in metabolic profile with slight amelioration of glucose metabolism
      regulation.

PMID- 20151763
TI  - The level of TSH appeared favourable in maintaining bone mineral density in
      postmenopausal women.
AB  - OBJECTIVE: Since the positive role of thyrotropin (TSH) in bone remodeling has
      been recently emphasized, this cross-section study is aimed to evaluate the
      association of bone status with the level of TSH and free thyroxine (FT4) in the
      cohort of postmenopausal women after long-term treatment of thyroid disorders and
      age matched controls. METHODS: Urinary calcium (dUCa) and serum level of TSH, FT4
      and of bone turnover markers (BTMs) such as alkaline phosphatase (ALP),
      osteocalcin (OC), cross linked N-telopeptide of type 1 collagen (NTx) as well as
      lumbar spine L 1-4 (BMD-L) and femoral hip (BMD-F) mineral density were
      determined in 113 postmenopausal women consisting of 42 patients with Graves
      disease treated by carbimazole, 32 patients with thyroid cancer treated with L
      thyroxine and 39 age matched women without any thyroid and osteological
      disorders. For statistical evaluation t-test, Pearson's correlation coefficient
      and linear multiple regression were used. RESULTS: To compare the association of
      TSH versus FT4 with BMD and BTMs the pooled cohort of all 113 women was divided
      in two groups in terms of TSH level: 1. 34 women with low TSH (>or=0.50 mU/l); 2.
      79 women with normal TSH (0.51-4.3 mU/l). In spite of significantly higher FT4
      level, the Group 2 with normal TSH level had significantly higher BMD-L and BMD-F
      (p<0.001) and, in contrast, significantly lower urinary dUCa, ALP, OC (all at
      p<0.001) and NTx (p<0.01) as compared to the Group 1 with low TSH level. Linear
      multiple regression showed highly significant influence of TSH on BMD-L and BMD
      F0 (p<0.001) independent of age, FT4 and body mass index, while that of FT4 was
      not significant. The strength of linear interrelation between all variables used
      was finally tested by Pearson's correlation coefficient (Table 3) which was
      highly positive for TSH with BMD-F and BMD-L, but highly negative for TSH with
      serum NTx, OC, ALP) and urinary calcium (dUCa). In contrast, no significant
      correlation was found between the level of FT4 and BMD. CONCLUSIONS:
      Irrespectively of FT4 level, postmenopausal women with normal TSH level showed a
      favorable bone status as compared to these with low level of TSH which is
      consistent with the view that TSH itself possibly participates in playing a
      favorable role in influencing the bone mineral density in adult women.

PMID- 20151764
TI  - Plasma levels of ICAM-1 and circulating endothelial cells are elevated in
      unstable types 1 and 2 diabetes.
AB  - OBJECTIVE: To investigate the expression and release of vascular cell-adhesion
      molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, endothelial
      leukocyte adhesion molecule (ELAM)-1 and von Willebrand factor (vWF), as well as
      circulating endothelial cells (CEC) and circulating endothelial progenitor cells
      (CEPC), as markers of endothelial dysfunction in uncontrolled, well controlled
      types 1 and 2 diabetic patients and non diabetic patients. METHODS: In this
      observational trans section study, soluble adhesion molecules concentrations were
      measured by enzyme linked immunosorbent assays and flow cytometry to detect
      circulating cells in 49 patients, stratified in 3 groups: G1: uncontrolled types
      1 and 2 diabetic patients (n=16); G2: well controlled diabetic (types 1 and 2)
      patients (n=13); and G3: non diabetic patients (n=20), of whom a blood sample was
      obtained on admission. RESULTS: ICAM-1 increased significantly in uncontrolled
      versus well controlled and non diabetic patients (721 vs. 702.45 vs. 473.46
      ng/ml, p=0.016). In unstable diabetic patients, CEC were higher than in the well
      controlled ones (7.75 vs. 4.3/ml, p=0.386) whereas CEPC were lower in unstable
      diabetics (56.5 vs. 72/ml, p=0.068). CONCLUSIONS: This study showed a continuous
      rise in ICAM-1 and CEC levels as stable, well controlled diabetic patients shift
      towards decompensation. In unstable diabetic patients, the relationship between
      CEC and CEPC can be represented as [CEC] alpha 1/[CEPC].

PMID- 20151765
TI  - Resistin and visfatin: regulators of insulin sensitivity, inflammation and
      immunity.
AB  - Adipokines play a significant role in the pathogenesis of a low-grade
      inflammation associated with obesity and metabolic syndrome, and in chronic
      inflammatory and autoimmune diseases such as rheumatoid arthritis. Among variety
      of adipokines, resistin and visfatin are proposed as important pro-inflammatory
      mediators, which also interfere with the central regulation of insulin
      sensitivity. Resistin has been initially postulated as a risk factor for insulin
      resistance, however, the subsequent available data on it have revealed
      contradictory findings in both humans and rodents. On the other hand, visfatin
      has been suggested to be a beneficial adipokine with insulin-mimicking/
      sensitizing effects, but regulation of visfatin production and its physiological
      importance in the conditions of obesity and type 2 diabetes mellitus are still
      not completely understood. Despite the opposing effects of resistin and visfatin
      on the regulation of insulin sensitivity, both adipokines have pro-inflammatory
      properties. Clinical and experimental studies have shown that the expression and
      secretion of resistin and visfatin are up-regulated during inflammation and in
      response to pro-inflammatory cytokines. It has also become increasingly evident
      that resistin as well as visfatin itself can contribute to the inflammatory
      processes by triggering cytokine production and NF-kappaB activation. New insight
      into the role of adipokines makes them attractive targets for novel therapeutic
      strategies in chronic inflammatory diseases or subclinical inflammation relating
      to obesity and various metabolic abnormalities.

PMID- 20151767
TI  - Reliability of stereoscopic nonmydriatic retinography for assessment of diabetic
      macular edema when performed by endocrinologists.
AB  - BACKGROUND: Diabetic macular edema (DME) is the main cause of moderate vision
      loss in type 2 diabetes. Diagnosis is achieved by dilated fundus examination or
      by measuring retinal thickness. However, it can be identified in nonmydriatic
      retinography (NMR) with hard exudates as a surrogate marker or macular thickness
      under stereoscopic vision. To date, few studies have focused on interobserver
      reliability for DME with this technique. METHODS: Fity-three type 2 diabetes
      patients with known diabetic retinopathy were studied. We obtained 182 pairs of
      stereoscopic retinographs with a nonmydriatic camera. Photographic options were
      30 degrees or 45 degrees macula-centered retinal field and spontaneous or
      pharmacological dilation using tropicamide. An endocrinologist with a minimum of
      training and another with no specific training in this kind of examination
      diagnosed the images. DME was assumed if retinal thickness was identified within
      one disc diameter around the fovea. RESULTS: The kappa index agreement between
      both endocrinologists for all the data was 0.16 (P = 0.02). Depending on the
      photographic options, all the kappa indices were below 0.25, except for the 45
      degrees retinal field under spontaneous mydriasis (0.58) where the number of
      samples analyzed was reduced to 22. CONCLUSIONS: In our study, endocrinologists
      with a low level of training did not reach a suitable level of agreement
      regarding the reliability of stereoscopic NMR as a technique for diagnosing DME.
      We feel that, as NMR can be performed by various different health providers, it
      would be advisable to establish generally agreed upon criteria for training staff
      in this technique.

PMID- 20151766
TI  - Timing of meal insulin boluses to achieve optimal postprandial glycemic control
      in patients with type 1 diabetes.
AB  - OBJECTIVE: This study determined the optimal timing of insulin bolus
      administration in relation to meal consumption in adolescents and adults with
      type 1 diabetes. STUDY DESIGN AND METHODS: Twenty-three subjects participated in
      this crossover study consisting of three treatment arms: delivering an insulin
      glulisine bolus by insulin pump 20 min prior to a meal ("PRE"), immediately
      before the meal ("START"), and 20 min after meal initiation ("POST"). Blood
      glucose levels were measured every 30 min for a total of 240 min post-meal
      initiation. Mean blood glucose levels at 1 and 2 h after meal initiation, blood
      glucose area under the curve (AUC), and maximum blood glucose levels were
      analyzed. RESULTS: At both 60 and 120 min after meal initiation, the PRE arm
      showed significantly lower glycemic excursions than the START arm (P = 0.0029 and
      0.0294, respectively) and the POST arm (P = 0.001 and 0.0408, respectively).
      Glycemic AUC was significantly less in the PRE arm versus both the START and POST
      arms (159.5 +/- 58.9 mg/dL vs. 187.0 +/- 43.1 mg/dL [P = 0.0297] and 184.5 +/-
      33.2 mg/dL [P = 0.0463], respectively). Peak blood glucose levels were
      significantly lower in the PRE arm compared to the START arm (P = 0.0039) and the
      POST arm (P = 0.0027). CONCLUSIONS: A bolus of rapid-acting insulin 20 min prior
      to a meal results in significantly better postprandial glucose control than when
      the meal insulin bolus is given just prior to the meal or 20 min after meal
      initiation.

PMID- 20151769
TI  - Evaluation of a glucose meter in determining the glycemic index of chinese
      traditional foods.
AB  - BACKGROUND: The purpose of this study was to evaluate whether the Glucometer
      Elite((R)) meter (Bayer Diagnostics, Kyoto, Japan) (POG) could be used for
      determining the glycemic index (GI) values of Chinese traditional foods, compared
      with the YSI (Yellow Springs, OH) glucose analyzer (YSI). METHODS: After
      consumption of either glucose or one of 11 test foods, the 2-h postprandial
      glucose responses were measured separately by POG and YSI. GI values and
      incremental area under the blood glucose response curve (IAUC) values were then
      calculated to make comparisons between POG and YSI. RESULTS: The mean glucose
      concentration measured by POG was higher than that measured by YSI (5.54 +/- 0.03
      vs. 5.30 +/- 0.03 mmol/L, P < 0.01). The mean IAUC calculated by POG data was
      also higher than that calculated by YSI data (112.93 +/- 4.04 vs. 106.76 +/- 4.06
      mmol.min/L, P < 0.01). However, there were no differences in the mean GI value
      determined by POG and YSI data for each test food. CONCLUSIONS: Although the
      glucose concentrations measured by POG were higher than that measured by YSI
      glucose analyzer, it seemed to be an appropriate instrument to determine the GI
      values of Chinese traditional foods. However, this conclusion should be
      cautiously applied to other kinds of glucose meters.

PMID- 20151768
TI  - Titration of inhaled human insulin (Exubera) in a treat-to-target regimen for
      patients with type 2 diabetes.
AB  - OBJECTIVE: This study assessed the feasibility of safely achieving target
      glycated hemoglobin (A1C) of < or =7% by intensifying structured insulin
      titration regimens using inhaled human insulin (Exubera [EXU] [Pfizer Inc., New
      York, NY] [insulin human (recombinant DNA origin)] inhalation powder) in patients
      with type 2 diabetes inadequately controlled on combination oral antidiabetes
      agents (OADs). METHODS: In a randomized, open-label, parallel, 24-week
      multicenter trial, 107 type 2 diabetes patients with mean baseline A1C of 8.6%
      taking two or more OADs were randomized to adjust EXU before meals following
      either weekly office visits or more intense twice-weekly telephone/office
      consultations, using a simple but structured insulin titration algorithm seeking
      to attain specific premeal glucose levels. Primary outcome was the percentage of
      patients reaching A1C < or =7%; secondary measures were changes in A1C, eight
      point self-monitored blood glucose values, postprandial glucose levels during a
      meal tolerance, and frequency of hypoglycemia. RESULTS: A1C improved whether EXU
      was systematically titrated once (6.8%) or twice weekly (6.8%), and two-thirds of
      patients in both groups attained A1C < or =7% (69% and 67%, respectively).
      Relative to baseline, glucose profiles were reduced at all time points measured,
      and postprandial glucose levels during meal tolerance improved to a similar
      extent in both groups. There were 538 hypoglycemic events with twice-weekly and
      343 with once-weekly EXU titration; other adverse events were similar between
      groups. CONCLUSIONS: Added to oral therapy, premeal inhaled insulin can safely
      achieve < or =7% A1C in most patients with type 2 diabetes inadequately
      controlled while taking two or more OADs if a once- or twice-weekly structured
      insulin titration regimen is used.

PMID- 20151770
TI  - Determining clinical and psychological benefits and barriers with continuous
      glucose monitoring therapy.
AB  - BACKGROUND: Preventing the complications of diabetes requires tight control and
      minimizing blood glucose fluctuation. Pursuing these goals increases the risk of
      severe hypoglycemia. The authors hoped to identify if using continuous glucose
      monitoring (CGM) decreased the incidence of severe hypoglycemia, resulted in less
      fear of hypoglycemia, and improved patient empowerment and what impact CCM had on
      quality of life (QOL) issues. METHODS: Questionnaires were used to gather
      demographic data, to measure educational experiences with CGM, QOL issues
      concerning fear of hypoglycemia and severe hypoglycemia, confidence to make
      changes to insulin regimens before and after using CGM, and the incidence of
      severe hypoglycemia before and while using CGM, and to assess the impact of CGM
      on QOL. RESULTS: The data and answers reported suggest significantly less fear of
      hypoglycemia and severe hypoglycemia and increased patient empowerment with CGM.
      Further shown is a reduced incidence of acute complications as evidenced by
      significantly decreased incidence of severe hypoglycemia. CGM appears to have a
      significant, positive impact on the stress associated with having and managing
      diabetes. CONCLUSIONS: Using CGM as part of the diabetes self-management plan
      offers the potential to significantly improve user outcomes as measured by QOL,
      reduction of fear, and patient empowerment. Using CGM can allow patients to
      achieve tighter control of their blood glucose values with reduced fear of
      hypoglycemia, reduced incidence of severe hypoglycemia, and a decreased sense of
      burden from having diabetes.

PMID- 20151772
TI  - Telemedicine intervention effects on waist circumference and body mass index in
      the IDEATel project.
AB  - BACKGROUND: We examine the changes in waist circumference (WC) and body mass
      index (BMI) in older adults enrolled in a diabetes telemedicine program. The
      subjects were elderly Medicare beneficiaries participating in the rural (upstate
      New York) cohort of Informatics and Diabetes Education and Telemedicine, a
      randomized, controlled trial using telemedicine to improve diabetes care in which
      the primary outcome was glycemic control. METHODS: Ninety-two percent of the
      subjects had BMI >25 kg/m(2), and 65.8% had a BMI > or =30 kg/m(2). Intervention
      subjects received home televisits with a dietitian or nurse educator every 4-6
      weeks. Blood glucose and blood pressure values were reviewed, and lifestyle and
      medication changes were recommended. Non-intervention subjects received usual
      care through their primary care physicians. Change in WC, BMI, diet, and exercise
      behaviors and knowledge were examined at baseline and 12 and 24 months. A mixed
      effects path analysis was performed to examine direct and indirect effects.
      RESULTS: The telemedicine participants increased diet and exercise knowledge over
      time (P < 0.001). It was estimated that women in the telemedicine group reduced
      their WC over the 2 years by 1.2 cm, whereas women in the usual care group
      increased their WC by almost 1 cm (P = 0.02). Path analysis demonstrated that the
      intervention, through improved diet and exercise knowledge, was related to the
      decrease in WC (P = 0.006) and BMI (P = 0.004). CONCLUSIONS: Diabetes case
      management using telemedicine improved self-reported diet and exercise knowledge,
      practices, and behaviors, which in turn was associated with reductions in WC and
      BMI at 2 years.

PMID- 20151775
TI  - The broken pen penalty.
AB  - Insulin pen devices have revolutionized the self-management of diabetes.
      Prefilled insulin pens are preferred by healthcare providers and patients because
      of ease-of-use, dosage flexibility, disposability, and widespread availability.
      However, like any mechanical device, these pens have the potential for mechanical
      malfunction. We are present a case in which glycemic control deteriorated because
      of a malfunction of an insulin pen. The possibility of insulin pen malfunction
      needs to be considered in addition to other factors in patients who present with
      acute deterioration of glycemic control.

PMID- 20151773
TI  - System accuracy evaluation of 27 blood glucose monitoring systems according to
      DIN EN ISO 15197.
AB  - BACKGROUND: Blood glucose (BG) monitoring systems enable diabetes patients to
      effectively control and adjust their therapy. BG monitoring systems with a
      Conformite Europeenne (CE) label should meet the standard DIN EN ISO 15197:2003:
      > or =95% of the BG results shall fall within +/-15 mg/dL of the reference method
      at BG concentrations <75 mg/dL and within +/-20% at BG concentrations > or =75
      mg/dL. We intended to verify if BG monitoring systems with a CE label fulfill
      these minimum accuracy requirements. METHODS: We evaluated 27 BG monitoring
      systems from 18 manufacturers for system accuracy according to DIN EN ISO
      15197:2003. Twenty-four systems were compared with the glucose oxidase reaction
      (YSI 2300 glucose analyzer [YSI Life Sciences, Yellow Springs, OH]) and three
      systems with the hexokinase reaction (Hitachi 917 [Roche Diagnostics GmbH,
      Mannheim, Germany]). Duplicate measurements of 100 blood samples with a defined
      distribution of BG concentrations from 20 mg/dL to 600 mg/dL from > or =100
      subjects were included in the evaluation. RESULTS: Sixteen of the 27 BG
      monitoring systems fulfilled the minimum accuracy requirements of the standard,
      i.e., > or =95% of their results showed the minimum acceptable accuracy. Overall,
      the mean percentage of results showing the minimum acceptable accuracy was 95.2
      +/- 5.2%, ranging from 80.0% to 100.0%. CONCLUSIONS: More than 40% of the
      evaluated BG monitoring systems did not fulfill the minimum accuracy requirements
      of DIN EN ISO 15197:2003. As inaccurate BG monitoring systems bear the risk of
      false treatment decisions by the diabetes patient and subsequent possible severe
      health injury, manufacturers should regularly and effectively check the quality
      of BG meters and BG test strips.

PMID- 20151777
TI  - Posterior interhemispheric transfalx transprecuneus approach to the atrium of the
      lateral ventricle: a cadaveric study.
AB  - OBJECT: The posterior interhemispheric transprecuneus gyrus approach is one of
      the surgical routes that has been suggested to reach the atrium of the lateral
      ventricle. It has the advantage of avoiding the disruption of the optic
      radiations; however, it has a narrow working area that at times makes the
      execution of this approach rather challenging. The aim of this study was to test
      a modification of the approach that might create a better surgical angle and a
      wider corridor by accessing the atrium from the contralateral side after
      transection of the falx. The authors named this new approach the "posterior
      interhemispheric transfalx transprecuneus approach." METHODS: The posterior
      interhemispheic transfalx transprecuneus approach was performed bilaterally on 6
      fresh adult cadaveric specimens for a total of 12 procedures. Every head was held
      in the semisitting position and a parasagittal parietooccipital craniotomy on the
      contralateral side of the targeted ventricle was executed. The dura mater was
      opened and reflected based on the sagittal sinus. Then the falx was cut in a
      triangular fashion based on the inferior sagittal sinus. Using the
      parietooccipital artery and sulcus as landmarks, the contralateral precuneus
      gyrus was indentified, and a small area of the gyrus was transected to gain
      access to the atrium. A neuronavigational system was also used to conduct this
      approach. The working angle of this approach and other distances were measured.
      RESULTS: The authors were able to visualize the ventricular atrium, posterior
      part of the temporal horn, pulvinar, and choroid plexus in all specimens. The
      temporal horn could be exposed for a length of 20-30 mm from the atrium. The
      working angle of the approach was better than that of the classic posterior
      interhemispheric transprecuneus approach with a mean value of 44.5 degrees  as
      opposed to 25.8 degrees . The distance from the middle point of the corticotomy
      to the splenium ranged from 11 to 16 mm (mean 13.3 mm); the distance to the
      torcula, from 34 to 53 mm (mean 41.3 mm); and the distance to the atrium, from 22
      to 31 mm (mean 25.7 mm). CONCLUSIONS: Results of this study suggested that the
      proposed approach can expose the atrium and the posterior part of the temporal
      horn of the lateral ventricle with a wider surgical angle compared with the
      conventional homolateral posterior interhemispheric transprecuneus gyrus
      approach. Moreover, by minimizing the amount of brain retraction homolateral to
      the target, this approach could make navigation more accurate.

PMID- 20151774
TI  - Exenatide versus glibenclamide in patients with diabetes.
AB  - BACKGROUND: Incretin-based therapies have provided additional options for the
      treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the
      effects of exenatide compared to glibenclamide on body weight, glycemic control,
      beta-cell function, insulin resistance, and inflammatory state in patients with
      diabetes. METHODS: One hundred twenty-eight patients with uncontrolled type 2
      diabetes mellitus receiving therapy with metformin were randomized to take
      exenatide 5 microg twice a day or glibenclamide 2.5 mg three times a day and
      titrated to exenatide 10 microg twice a day or glibenclamide 5 mg three times a
      day. We evaluated body weight, body mass index (BMI), glycated hemoglobin
      (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG),
      fasting plasma insulin (FPI), homeostasis model assessment insulin resistance
      (HOMA-IR) index, homeostasis model assessment beta-cell function (HOMA-beta)
      index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein
      4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after
      3, 6, 9, and 12 months. RESULTS: Body weight and BMI decreased with exenatide and
      increased with glibenclamide. A similar improvement of HbA(1c), FPG, and PPG was
      obtained in both groups, whereas FPI decreased with exenatide and increased with
      glibenclamide. The HOMA-IR index decreased and the HOMA-beta index increased with
      exenatide but not with glibenclamide. A decrease of PPr was reported in both
      groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4
      decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP
      was obtained with exenatide, whereas no variations were observed with
      glibenclamide. CONCLUSIONS: Both exenatide and glibenclamide gave a similar
      improvement of glycemic control, but only exenatide gave improvements of insulin
      resistance and beta-cell function, giving also a decrease of body weight and of
      inflammatory state.

PMID- 20151782
TI  - Selection of patients with idiopathic normal-pressure hydrocephalus for shunt
      placement: a single-institution experience.
AB  - OBJECT: The ability to predict outcome after shunt placement in patients with
      idiopathic normal-pressure hydrocephalus (NPH) represents a challenge. To date,
      no single diagnostic tool or combination of tools has proved capable of reliably
      predicting whether the condition of a patient with suspected NPH will improve
      after a shunting procedure. In this paper, the authors report their experience
      with 120 patients with the goal of identifying CSF hydrodynamics criteria capable
      of selecting patients with idiopathic NPH. Specifically, they focused on the
      comparison between CSF-outflow resistance (R-out) and intracranial elastance
      (IE). METHODS: Between January 1977 and December 2005, 120 patients in whom
      idiopathic NPH had been diagnosed (on the basis of clinical findings and imaging)
      underwent CSF hydrodynamics evaluation based on an intraventricular infusion
      test. Ninety-six patients underwent CSF shunt placement: 32 between 1977 and 1989
      (Group I) on the basis of purely clinical and radiological criteria; 44 between
      1990 and 2002 (Group II) on the basis of the same criteria as Group I and because
      they had an IE slope > 0.25; and 20 between 2003 and 2005 (Group III) on the
      basis of the same criteria as Group II but with an IE slope > or = 0.30. Outcomes
      were evaluated by means of both Stein-Langfitt and Larsson scores. Patients'
      conditions were considered improved when there was a stable decrease (at 6- and
      12-month follow-up) of at least 1 point in the Stein-Langfitt score and 2 points
      in the Larsson score. RESULTS: Group I: while no statistically significant
      difference in mean R-out value between improved and unimproved cases was
      observed, a clear-cut IE slope value of 0.25 differentiated very sharply between
      unimproved and improved cases. Group II: R-out values in the 2 unimproved cases
      were 20 and 47 mm Hg/ml/min, respectively. The mean IE slope in the improved
      cases was 0.56 (range 0.30-1.4), while the IE slopes in the 2 unimproved cases
      were 0.26 and 0.27. Group III: the mean IE slope was 0.51 (range 0.31-0.7). The
      conditions of all patients improved after shunting. A significant reduction of
      the Evans ratio was observed in 34 (40.5%) of the 84 improved cases and in none
      of the unimproved cases. CONCLUSIONS: Our strategy based on the analysis of CSF
      pulse pressure parameters seems to have a great accuracy in predicting surgical
      outcome in clinical practice.

PMID- 20151781
TI  - Contralateral approach to the atrium of the lateral ventricle.

PMID- 20151771
TI  - Feasibility of assessing liver lipid by proton magnetic resonance spectroscopy in
      healthy normal and overweight prepubertal children.
AB  - BACKGROUND: Intramyocellular and intrahepatic (IHL) lipids are significantly
      associated with insulin resistance in adults and adolescents and may represent an
      early marker for developing the metabolic syndrome or type 2 diabetes. METHODS:
      During the pilot phase of a larger cross-sectional study, we used proton magnetic
      resonance spectroscopy ((1)H-MRS) to determine the feasibility of noninvasively
      evaluating IHL in 11 male (n = 4) and female (n = 7) prepubertal children using a
      standard clinical system and to determine whether IHL is correlated with
      adiposity, fasting insulin and glucose, and liver enzymes. RESULTS: Body mass
      index (BMI) (range, 13.4-32.4 kg/m(2)) and IHL stores (range, 0.07-3.2% relative
      to an oil phantom) were variable. IHL was correlated with body mass (r = 0.66, P
      = 0.037), BMI (r = 0.73, P = 0.016), percentage body fat (r = 0.73, P = 0.01, n =
      10), waist circumference (r = 0.85, P = 0.016), and serum lactate dehydrogenase
      concentration (r = 0.77, P = 0.03) but was not significantly correlated with
      other markers of liver damage, including aspartate aminotransferase activity (r =
      0.59, P = 0.09, n = 9) and alkaline phosphatase concentrations (r = 0.60, P =
      0.087). IHL was also (P < 0.01) correlated with fasting insulin concentration (r
      = 0.85, P = 0.03, n = 6) and insulin resistance (r = 0.94, P = 0.006, n = 6), but
      these correlations were driven by the results for one child. CONCLUSIONS: These
      preliminary data suggest that (1)H-MRS obtained in a standard pediatric clinical
      environment may be used to determine IHL in healthy normal and overweight
      prepubertal youth. This noninvasive technique may prove useful in identifying
      early markers of the metabolic syndrome in at-risk youth.

PMID- 20151778
TI  - Development of and psychometric testing for the Brief Pain Inventory-Facial in
      patients with facial pain syndromes.
AB  - OBJECT: Outcomes in clinical trials on trigeminal pain therapies require
      instruments with demonstrated reliability and validity. The authors evaluated the
      Brief Pain Inventory (BPI) in its existing form plus an additional 7 facial
      specific items in patients referred to a single neurosurgeon for a diagnosis of
      facial pain. The complete 18-item instrument is referred to as the BPI-Facial.
      METHODS: This study was a cross-sectional analysis of patients who completed the
      BPI-Facial. The diagnosis of classic versus atypical trigeminal neuralgia (TN)
      was made before analyzing the questionnaire results. A hypothesis-driven factor
      analysis was used to determine the principal components of the questionnaire.
      Item reliability and questionnaire validity were tested for these specific
      constructs. RESULTS: Data from 156 patients were analyzed, including 114 patients
      (73%) with classic and 42 (27%) with atypical TN. Using orthomax rotation factor
      analysis, 3 factors with an eigenvalue > 1.0 were identified-pain intensity,
      interference with general activities, and facial-specific pain interference
      accounting for 97.6% of the observed item variance. Retention of the 3 factors
      was confirmed via a Cattell scree plot. Internal reliability was demonstrated by
      calculating Cronbach's alpha: 0.86 for pain intensity, 0.89 for interference with
      general activities, 0.95 for facial-specific pain interference, and 0.94 for the
      entire instrument. Initial validity of the BPI-Facial instrument was supported by
      the detection of statistically significant differences between patients with
      classic versus atypical pain. Patients with atypical TN rated their facial pain
      as more intense (atypical 6.24 vs classic 5.03, p = 0.013) and as having greater
      interference in general activities (atypical 6.94 vs classic 5.43, p = 0.0033).
      Both groups expressed high levels of facial-specific pain interference (atypical
      6.34 vs classic 5.95, p = 0.527). CONCLUSIONS: The BPI-Facial is a rigorous
      measure of facial pain in patients with TN and appears to have sound psychometric
      properties and is responsive to differences between classic and atypical TN.
      Future studies must assess the instrument's test-retest reliability, validity in
      additional populations, and responsiveness with respect to changes in patient
      outcomes following neurosurgical interventions and medical therapies.

PMID- 20151785
TI  - Dosing, efficacy and safety plus the use of computerized photography for
      botulinum toxins type A for upper facial lines.
AB  - INTRODUCTION: Several studies confirm that botulinum toxins type A (BTX-A) are
      effective for reducing facial lines caused by hyperactive muscles. Two different
      commercial types of BTX-A currently available are BTX-A-1 (Botox) and BTX-A-2
      (Dysport). This paper reports further comparison of dosing, efficacy and safety.
      METHODS: Sites treated: glabellar, horizontal forehead lines and crow's feet.
      Different dilutions and dosages were studied with BTX-A-1 and BTX-A-2. The
      reduction of facial lines was evaluated by investigators and patients.
      Computerized photographic numerical assessment was also studied in determining
      the efficacy of BTX-A for crow's feet lines. RESULTS: Study 1: Injecting
      glabellar lines at doses of BTX-A-1 (30 units) and BTX-A-2 (75 units) (2.5:1
      ratio BTX-A2:BTX-A1) showed similar efficacy. Study 2: BTX-A-2 (256 units total)
      was significantly more effective than BTX-A-1 (64 units total) (i.e. a dose ratio
      of 4:1) for upper face lines. No differences in the side-effect profiles between
      the two toxins were observed in either study. Study 3: A computerized
      photographic numerical assay was an objective assessment of crow's feet severity.
      Using a dose ratio of BTX-A-2 to BTX-A-1 of 3:1 showed a trend towards BTX-A-2
      superiority. CONCLUSION: Two different botulinum toxins type A were shown to be
      effective and safe for hyperfunctional facial lines. The choice of dose, dilution
      and placement is critical for each individual toxin. Computerized photography
      gave numerical severity scores of crow's feet severity.

PMID- 20151780
TI  - The interperiosteo-dural concept applied to the perisellar compartment: a
      microanatomical and electron microscopic study.
AB  - OBJECT: The dura mater has 2 dural layers: the endosteal layer (outer layer),
      which is firmly attached to the bone, and the meningeal layer (inner layer),
      which directly covers the brain. These 2 dural layers join together in the middle
      temporal fossa or the convexity and separate into the orbital, lateral sellar
      compartment (LSC), or spinal epidural space to form the extradural neural axis
      compartment (EDNAC). The aim of this work was to anatomically verify the concept
      of the EDNAC by using electron microscopy. METHODS: The authors studied the
      cadaveric heads obtained from 13 adults. Ten of the specimens (or 20 perisellar
      areas) were injected with colored latex and fixed in formalin. They carefully
      removed each brain to allow a superior approach to the perisellar area. The 3
      other specimens were studied by microscopic and ultrastructural methods to
      describe the EDNAC in the perisellar area. Special attention was paid to the
      dural layers surrounding the perisellar area. The authors studied the anatomy of
      the meningeal architecture of the LSC, the petroclival venous confluence, the
      orbit, and the trigeminal cave. After dissection, the authors took photographs of
      the dural layers with the aid of optical magnification. The 3 remaining heads,
      obtained from fresh cadavers, were prepared for electron microscopic study.
      RESULTS: The EDNAC is limited by the endosteal layer and the meningeal layer and
      contains fat and/or venous blood. The endosteal layer and meningeal layer were
      not identical on electron microscopy; this finding can be readily related to the
      histology of the meninges. CONCLUSIONS: In this study, the authors demonstrated
      the existence of the EDNAC concept in the perisellar area by using dissected
      cadaveric heads and verified the reality of the concept of the meningeal layer
      with electron microscopy. These findings clearly demonstrated the existence of
      the EDNAC, a notion that has generally been accepted but never demonstrated
      microscopically.

PMID- 20151786
TI  - Dosing accuracy of commonly used disposable insulin pens.
AB  - OBJECTIVE: The present study aimed to assess the dosing accuracy of commonly used
      disposable insulin pens including SoloStar (SR)*, FlexPen (FP) dagger, Next
      Generation FlexPen (NGFP) dagger, and KwikPen (KP) double dagger. It is the first
      comparative study covering the whole dosing range from 1 U to 60 U. It also
      covers the accuracy of SR at 80 U. RESEARCH DESIGN AND METHOD: A total of sixty
      insulin pens from two lots of each pen type were used. From each pen 1 U, 10 U,
      30 U, 40 U, 60 U and 80 U were dispensed in random order. The 80 U dose was only
      evaluated for the SR as the other insulin pens do not deliver this dose in one
      injection. The actual doses were determined gravimetrically taking density of the
      different insulin preparations into account. The evaluation of dose accuracy was
      based on the regulations of the International Organization for Standardization
      (DIN EN ISO 11608-1:2000). RESULTS: All tested insulin pens met the requirements
      for accuracy with none of the single values at all dose levels being outside the
      defined range of the ISO recommendations (1 +/- 1 U, 10 +/- 1 U, 30 +/- 1.5 U, 40
      +/- 2 U, 60 +/- 3 U and 80 +/- 4 U). For the investigated dosage levels the
      absolute average deviation of all insulin pens ranged between 0.09 and 0.81 U.
      CONCLUSION: The present study demonstrates an excellent dosing accuracy for all
      tested insulin pens, with no clinically relevant differences between the
      products.

PMID- 20151779
TI  - Parasellar compartment.

PMID- 20151790
TI  - Dental therapy programs.

PMID- 20151783
TI  - Seeding neural progenitor cells on silicon-based neural probes.
AB  - OBJECT: Chronically implanted neural electrode arrays have the potential to be
      used as neural prostheses in patients with various neurological disorders. While
      these electrodes perform well in acute recordings, they often fail to function
      reliably in clinically relevant chronic settings because of glial encapsulation
      and the loss of neurons. Surface modification of these implants may provide a
      means of improving their biocompatibility and integration within host brain
      tissue. The authors proposed a method of improving the brain-implant interface by
      seeding the implant's surface with a layer of neural progenitor cells (NPCs)
      derived from adult murine subependyma. Neural progenitor cells may reduce the
      foreign body reaction by presenting a tissue-friendly surface and repair implant
      induced injury and inflammation by releasing neurotrophic factors. In this study,
      the authors evaluated the growth and differentiation of NPCs on laminin
      immobilized probe surfaces and explored the potential impact on transplant
      survival of these cells. METHODS: Laminin protein was successfully immobilized on
      the silicon surface via covalent binding using silane chemistry. The growth,
      adhesion, and differentiation of NPCs expressing green fluorescent protein (GFP)
      on laminin-modified silicon surfaces were characterized in vitro by using
      immunocytochemical techniques. Shear forces were applied to NPC cultures in
      growth medium to evaluate their shearing properties. In addition, neural probes
      seeded with GFP-labeled NPCs cultured in growth medium for 14 days were implanted
      in murine cortex. The authors assessed the adhesion properties of these cells
      during implantation conditions. Moreover, the tissue response around NPC-seeded
      implants was observed after 1 and 7 days postimplantation. RESULTS: Significantly
      improved NPC attachment and growth was found on the laminin-immobilized surface
      compared with an unmodified control before and after shear force application. The
      NPCs grown on the laminin-immobilized surface showed differentiation potential
      similar to those grown on polylysine-treated well plates, as previously reported.
      Viable (still expressing GFP) NPCs were found on and in proximity to the neural
      implant after 1 and 7 days postimplantation. Preliminary examinations indicated
      that the probe's NPC coating might reduce the glial response at these 2 different
      time points. CONCLUSIONS: The authors' findings suggest that NPCs can
      differentiate and strongly adhere to laminin-immobilized surfaces, providing a
      stable matrix for these cells to be implanted in brain tissue on the neural
      probe's surface. In addition, NPCs were found to improve the astrocytic reaction
      around the implant site. Further in vivo work revealing the mechanisms of this
      effect could lead to improvement of biocompatibility and chronic recording
      performance of neural probes.

PMID- 20151791
TI  - Effect of a health education program on climacteric women.
AB  - AIM: To evaluate the effect of a health education program on climacteric women
      from the viewpoint of health improvement and maintenance. METHODS: Twenty-two
      climacteric women (aged 45-65 years) acted as the intervention group and attended
      six seminars about health care; data were collected by the Simplified Menopausal
      Index (SMI), the Hospital Anxiety and Depression Scale (HADS) and the MOS 36-Item
      Short-Form Health Survey (SF-36). Changes in recognition action were evaluated
      using pre-test, post-test and follow-up questionnaires, and the activity of the
      autonomic nervous system (ANS) was measured by heart rate variability. Thirty
      women acting as controls were also given the same questionnaires. RESULTS: The
      SMI score was significantly improved at post-test and at follow-up compared to
      pre-test values, and the post-test HADS (total) score of the intervention group
      tended to improve. At the quality-of-life level, general post-test health
      perceptions significantly improved and role physical/role emotional significantly
      improved at follow-up. Cognitive behavioral changes in the intervention group
      were significantly improved according to self-reports and the ANS was also
      activated. CONCLUSION: The health education program changed the cognitive actions
      of climacteric women, which resulted in continuously improved menopausal
      symptoms, quality of life and autonomic nervous system activity.

PMID- 20151788
TI  - Dizygotic twin pregnancy with a normal fetus and a nodular embryo associated with
      a partial hydatidiform mole.
AB  - Although twin pregnancies complicated by a coexisting complete hydatidiform mole
      are uncommon, those with partial hydatidiform mole (PHM) are exceedingly rare;
      there are only several well-documented cases diagnosed antenatally. Here we
      present the first case of a twin placenta containing a nodular embryo associated
      with PHM diagnosed on routine placental examination. This dizygotic twin
      pregnancy featured viable embryos at 8 weeks' gestation, death of 1 embryo at 12
      weeks, and delivery of a healthy infant by caesarean section at 28 weeks because
      of worsening maternal reflux nephropathy. Macroscopic and microscopic placental
      examination and fluorescence in situ hybridization showed one part of the
      placenta to be diploid and the other to contain a vanishing triploid embryo and a
      PHM, which had eluded antenatal ultrasound diagnosis. Careful pathologic
      examination of vanishing twins and their placentas may disclose an unexpected
      PHM, which can be associated, albeit infrequently, with persistent gestational
      trophoblastic disease or a trophoblastic tumor.

PMID- 20151776
TI  - Results of excision of cerebral radionecrosis: experience in patients treated
      with radiation therapy for nasopharyngeal carcinoma.
AB  - OBJECT: In theory, the purpose of the treatment of cerebral radionecrosis (CRN),
      a nonneoplastic condition, is to minimize loss of brain function by preventing
      the progression and reversing some of the processes of CRN. In a practical sense,
      factors for achieving this purpose may include the following: removal of a CRN
      lesion that is causing mass effect, control of brain edema, prevention of
      recurrence of CRN lesions, minimization of adverse effects from treatments, and
      achievement of reasonably long and good-quality survivals. Based on these
      practical issues, the authors performed a retrospective study to evaluate the
      results of excision for the treatment of CRN. METHODS: The authors
      retrospectively reviewed the results of excision of CRN lesions in a group of
      patients with temporal lobe CRN due to radiotherapy for nasopharyngeal carcinoma.
      Patients who had undergone surgery at the authors' institution between January
      1998 and November 2008 were analyzed. Surgical results were evaluated by
      assessing postoperative resolution of brain edema, recurrence of temporal lobe
      CRN, surgery-related complications, and postoperative functional status and
      survival. RESULTS: Twenty-four patients were included (age range 39-69 years; in
      23 patients nasopharyngeal carcinoma was in remission). All patients underwent
      craniotomy for excision of the contrast-enhancing region. The indications for
      operation were temporal lobe CRN lesions with a mass-occupying effect beyond the
      temporal lobe. There were 32 craniotomies in all (mean postoperative follow-up 40
      months). It was found that brain edema resolved rapidly postoperatively. The
      recurrence and reoperation rates were 6.3 and 3.1%, respectively. There were no
      surgery-related deaths. The median survival was 72 months, and 67% of the
      patients had a Karnofsky Performance Scale score of > or = 70% at the time of
      their last follow-up. CONCLUSIONS: In a specific group of patients with CRN of
      the temporal lobe in whom the CRN lesions were causing a mass-occupying effect
      beyond the temporal lobe, excision of the contrast-enhancing region was safe and
      could achieve prompt resolution of brain edema and a low incidence of recurrence
      of CRN.

PMID- 20151792
TI  - Effect of abrupt discontinuation versus gradual dose reduction of postmenopausal
      hormone therapy on hot flushes.
AB  - OBJECTIVE: To compare the effects of the abrupt discontinuation of postmenopausal
      hormone therapy (HT) and reduction of the daily dosage of the hormone on
      climacteric symptoms. METHODS: The study included Brazilian postmenopausal women
      who were using estrogen-progestogen hormone therapy in full doses previously
      prescribed for vasomotor symptoms. The patients were randomized to receive one of
      three treatments: placebo for 6 months; estradiol (E2) 1 mg/day + norethisterone
      acetate (NETA) 0.5 mg/day for 2 months, followed by placebo for 4 months; or E2 1
      mg/day + NETA 0.5 mg/day for 4 months, followed by placebo for 2 months. The
      climacteric symptoms were assessed by the Blatt-Kupperman Menopausal Index at
      baseline and at 2, 4 and 6 months. Statistical evaluation was performed using the
      chi(2) or Fisher's test for categorical data, the Kruskal-Wallis test for
      numerical data, and ANOVA for time and group relationship with the Blatt
      Kupperman Menopausal Index. RESULTS: We randomized 60 women (20 in each group),
      and 54 completed the study. It was observed that both the full Blatt-Kupperman
      Menopausal Index and the hot flush score did not change significantly in the HT
      group during low-dose therapy compared with baseline; however, the evaluation
      performed at 2 months after low-dose-HT cessation showed that the full Blatt
      Kupperman Menopausal Index and the hot flush score were similar to those of the
      group who stopped HT abruptly and significantly higher than at baseline (hot
      flush scores: p < 0.001 for all three groups at months 2, 4 and 6, respectively,
      vs. baseline). CONCLUSION: Discontinuation of HT by reducing the daily dose of
      estrogen for a period of 2 or 4 months did not differ in its effect from that of
      abrupt cessation with regard to vasomotor symptoms.

PMID- 20151784
TI  - Lateral sellar angiolipoma: a tumor illustrative of the extradural compartment of
      the neural axis.
AB  - Angiolipomas are rare tumors of the CNS that most frequently develop in the
      orbit, the cavernous space, and the epidural space of the spine. The authors
      report the case of a patient who presented with an angiolipoma of the cavernous
      space. Using data from the published literature and an experimental anatomical
      approach, they demonstrate that the cavernous space contains adipose tissue.
      Consequently, they suggest that angiolipomas constitute a characteristic tumor
      illustrating the interperiosteo-dural concept. The authors report the clinical,
      radiological, and histological data of a patient who presented with a tumor of
      the cavernous space. In addition, they prepared 2 encephalic extremities (4
      cavernous spaces) using a special anatomical preparation consisting of an
      injection of colored neoprene latex followed by a 6-month immersion in a
      formaldehyde solution enriched with hydrogen peroxide to soften the bone
      structures (coronal sections) while leaving the fat in the cavernous space
      intact. This case report corroborates previously published clinical data and
      shows that the tumor was a hamartoma comprising mature fat cells associated with
      vascular proliferation. The tumor developed in the cavernous space, which is an
      interperiosteo-dural space extending from the sphenoid periosteum
      (osteoperiosteal layer) to the superior and lateral walls of the cavernous space
      (encephalic layer). This space represents an anatomical continuum extending from
      the coccyx to the orbit: the interperiosteo-dural concept. It contains fat tissue
      that is abundant at the level of the orbit and the epidural spinal space and
      sparser at the level of the cavernous spaces, as was shown in our anatomical
      study. The authors suggest that angiolipomas represent a characteristic tumor
      that illustrates the interperiosteo-dural concept because they essentially
      develop in the fat tissue contained in these spaces.

PMID- 20151787
TI  - Effects of intranasal xylometazoline, alone or in combination with ipratropium,
      in patients with common cold.
AB  - BACKGROUND: Common cold is one of the most prevalent conditions that family
      doctors encounter. One of the first symptoms to occur is nasal congestion, which
      can have a negative impact on daily life and prompts many patients to seek
      treatment for relief. Xylometazoline nasal spray (Otrivin*) is a topical
      decongestant that has been used successfully for many years and is generally
      recognized as an effective and safe therapy. However, most studies have
      investigated its clinical efficacy in healthy patients and few have included
      patients with common cold. SCOPE: To review the published clinical efficacy and
      safety of xylometazoline alone and in combination in the management of nasal
      congestion in patients with common cold. Literature searches of PubMed and the
      Cochrane Library were conducted to obtain published open or blinded, randomized,
      placebo- or active-controlled studies on the use of xylometazoline hydrochloride
      for the symptomatic relief of nasal congestion in patients with common cold.
      Searches included papers published in English only, up to September 2009.
      FINDINGS: Despite the small number of studies identified in common cold (n = 4),
      as per search criteria defined, intranasal xylometazoline quickly and effectively
      relieved nasal congestion. When used alone, xylometazoline had a clinically
      relevant decongestant effect that was significantly superior for up to 10 hours
      compared with placebo. The superior decongestant effect with xylometazoline led
      to high patient satisfaction with treatment. When used in combination with
      ipratropium bromide, nasal congestion and rhinorrhoea were treated
      simultaneously, leading to significantly higher patient general impression scores
      compared with either agent used alone. Xylometazoline was well tolerated, with
      generally mild to moderate nasal-related side effects (e.g. epistaxis in 3.4% of
      patients, and blood-tinged mucus in 10-26% of patients) that were easily
      resolved; the most frequently reported non-nasal AEs were headache (3.4%) and
      period pain (10.3%); no cases of sedation were reported. As expected, no rhinitis
      medicamentosa or rebound congestion was noted with short-term use (<10 days). No
      clinically important differences in ciliary motility and mucociliary clearance
      were observed. Xylometazoline does not result in sympathomimetic systemic side
      effects seen with oral decongestants (e.g. pseudoephedrine, phenylephrine).
      CONCLUSIONS: The few studies available in common cold suggest that intranasal
      xylometazoline provides fast and effective relief of nasal congestion and is well
      tolerated. When xylometazoline is used in combination with ipratropium, patients
      with common cold experience the additive benefit of nasal congestion and
      rhinorrhoea being treated simultaneously.

PMID- 20151794
TI  - To the editor: Re: "The American Journal of Cardiology and Journal of
      Periodontology Editors' Consensus:Periodontitis and Atherosclerotic
      Cardiovascular Disease".

PMID- 20151798
TI  - Periodontal diseases, preterm births, and low birth weight: findings from a
      homogeneous cohort of women in Madagascar.
AB  - BACKGROUND: Studies on the possible influence of periodontal disease on preterm
      birth (PB) and/or low birth weight (LBW) remain inconclusive especially due to
      the difficulty of assessing the numerous pregnancy risk factors. The aim of this
      study is to compare periodontal parameters in non-smoking pregnant women in
      Madagascar. METHODS: A cohort study with 204 pregnant women (mean age: 25.6
      years) was conducted in public prenatal care health clinics in Madagascar.
      Socioeconomic and obstetric information was obtained. Periodontal parameters,
      such as periodontal probing depth and clinical attachment loss (AL), were
      recorded during the second semester of pregnancy. RESULTS: The mean gestational
      age was 37.8 weeks. At delivery, 42 newborns (20.6%) were PBs (<37 weeks) and 22
      newborns (10.8%) were of LBW (<2,500 g). Nine (4.4%) newborns were PBs and of LBW
      (PLBW), and 149 newborns (73%) were of normal birth. The mean plaque index and
      papillary bleeding index were significantly higher (P <0.05 and P <0.001,
      respectively) in the PB group than in the normal birth group. Periodontitis (at
      least three sites from different teeth with clinical AL >or=4 mm) was
      significantly associated with PB (P <0.001), LBW (P <0.001), and PLBW (P <0.01).
      The rates of periodontitis were considerably higher in PB (78.6%), LBW (77.3%),
      and PLBW (77.8%) groups than in the full-term (8.6%), normal weight (16.5%), and
      normal birth (2.7%) groups. CONCLUSION: The strong association among
      periodontitis, PB, and LBW in this study highlights the need to consider the
      periodontal status of pregnant women in Madagascar.

PMID- 20151800
TI  - Association of periodontitis with rheumatoid arthritis: a pilot study.
AB  - BACKGROUND: Similarities exist in the epidemiology and immunopathogenesis of
      periodontitis and rheumatoid arthritis (RA), but the associations between their
      respective disease activities and severities are less well documented. We
      evaluated the prevalence and severity of periodontitis in United States (U.S.)
      veterans with RA and their relationship to RA disease activity and severity.
      METHODS: Patients with RA from an outpatient rheumatology clinic were eligible,
      and patients with osteoarthritis (OA) served as controls. Dentists, masked to the
      rheumatologic diagnoses, performed periodontal probing and examined dental
      panoramic radiographs to assess the presence and severity of periodontitis.
      Associations of periodontitis with RA were examined using multivariate
      regression, whereas the association of periodontitis with disease-severity
      measures in RA was examined using the chi(2) test. RESULTS: Sixty-nine patients
      with RA (57 males and 12 females) and 35 patients with OA (30 males and five
      females) were studied. Moderate to severe periodontitis was more prevalent in
      patients with RA (51%) than controls (26%) (P = 0.03), an association independent
      of age, race, smoking, diabetes mellitus, and gender. Patients with RA who were
      seropositive for rheumatoid factor (RF) were more likely to have moderate to
      severe periodontitis (59%) than patients who were RF negative (15%) (P = 0.02).
      Likewise, patients with RA who were positive for the anti-cyclic citrullinated
      peptide (CCP) antibodies were more likely to have moderate to severe
      periodontitis (56%) than patients who were anti-CCP negative (22%) (P = 0.01).
      There were no associations of periodontitis status with other measures of RA
      disease activity or severity. CONCLUSIONS: In a cohort of U.S. veterans,
      periodontitis was more common and severe in patients with RA compared to patients
      with OA. Although unrelated to disease activity, the presence of periodontitis in
      patients with RA was associated with seropositivity for RF and the anti-CCP
      antibody, which was highly relevant given the associations of these
      autoantibodies with poor outcomes and disease pathogenesis in RA.

PMID- 20151799
TI  - Clinical effect of subgingivally delivered simvastatin in the treatment of
      patients with chronic periodontitis: a randomized clinical trial.
AB  - BACKGROUND: Periodontitis is an inflammatory disease that results in bone
      resorption creating bony defects, which may cause tooth loss. Various drugs have
      been studied using local delivery to improve the periodontal health and to
      achieve periodontal regeneration. Simvastatin (SMV) is a specific competitive
      inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. The present study
      was designed to investigate the effectiveness of SMV, 1.2 mg, in an indigenously
      prepared biodegradable controlled-release gel as an adjunct to scaling and root
      planing (SRP) in the treatment of chronic periodontitis. METHODS: Sixty patients
      were categorized into two treatment groups: SRP plus placebo (group 1) and SRP
      plus SMV, 1.2 mg (group 2). Clinical parameters were recorded at baseline before
      SRP and at 1, 2, 4, and 6 months; they included modified sulcus bleeding index
      (mSBI), probing depth (PD), and clinical attachment level (CAL). At baseline and
      after 6 months, radiologic assessment of intrabony defect (IBD) fill was done
      using computer-aided software. The mean concentration of SMV in gingival
      crevicular fluid was estimated by reverse-phase high-performance liquid
      chromatography. RESULTS: All subjects tolerated the drug, without any
      postapplication inflammation. Both therapies resulted in significant
      improvements. The decrease in mSBI score at 6 months was greater in group 2
      (2.3267 +/- 0.8017) compared to group 1 (0.5033 +/- 0.6815). The mean decrease in
      PD from baseline to 6 months was 1.20 +/- 1.24 mm and 4.26 +/- 1.59 mm in groups
      1 and 2, respectively. Mean CAL gain from baseline to 6 months was 1.63 +/- 1.99
      mm and 4.36 +/- 1.92 mm in groups 1 and 2, respectively. In group 2, there was
      greater decrease in mean IBD (1.41 +/- 0.74 mm or 32.54%) compared to group 1
      (0.09 +/- 0.58 mm or 2.16%). CONCLUSION: There was a greater decrease in gingival
      index and PD and more CAL gain with significant IBD fill at sites treated with
      SRP plus locally delivered SMV in patients with chronic periodontitis.

PMID- 20151796
TI  - An update on novel non-invasive approaches for periodontal diagnosis.
AB  - For decades there has been an ongoing search for clinically acceptable methods
      for the accurate, non-invasive diagnosis and prognosis of periodontitis. There
      are several well-known inherent drawbacks with current clinical procedures. The
      purpose of this review is to summarize some of the newly emerging diagnostic
      approaches, namely, infrared spectroscopy, optical coherence tomography (OCT),
      and ultrasound. The history and attractive features of these new approaches are
      briefly illustrated, and the interesting and significant inventions related to
      dental applications are discussed. The particularly attractive aspects for the
      dental community are that some of these methods are totally non-invasive, do not
      impose any discomforts to the patients during the procedure, and require no
      tissue to be extracted. For instance, multiple inflammatory indices withdrawn
      from near infrared spectra have the potential to identify early signs of
      inflammation leading to tissue breakdown. Morphologically, some other non
      invasive imaging modalities, such as OCT and ultrasound, could be employed to
      accurately measure probing depths and assess the status of periodontal
      attachment, the front-line of disease progression. Given that these methods
      reflect a completely different assessment of periodontal inflammation, if
      clinically validated, these methods could either replace traditional clinical
      examinations for the diagnosis of periodontitis or at least serve as attractive
      complementary diagnostic tools. However, the potential of these techniques should
      be interpreted more cautiously given the multifactorial character of periodontal
      disease. In addition to these novel tools in the field of periodontal
      inflammatory diseases, other alternative modalities like microbiologic and
      genetic approaches are only briefly mentioned in this review because they have
      been thoroughly discussed in other comprehensive reviews.

PMID- 20151797
TI  - Periodontal disease, oxidative stress, and risk for preeclampsia.
AB  - BACKGROUND: Maternal periodontal infection is associated with an increased risk
      for preeclampsia. Periodontal infection is also associated with increased
      oxidative stress. Our objective was to determine the relationship among maternal
      periodontal disease, maternal oxidative stress, and the development of
      preeclampsia. METHODS: A secondary analysis of prospectively collected data from
      the Oral Conditions and Pregnancy Study was performed. A cohort of healthy women
      enrolled at <26 weeks of gestation underwent an oral examination, serum sampling,
      and delivery follow-up. A periodontal infection was categorized by clinical
      parameters as healthy or mild or moderate/severe periodontal infection.
      Preeclampsia was defined by the American Congress of Obstetricians and
      Gynecologists criteria as blood pressure >140/90 mmHg and >or=1+ proteinuria on a
      catheterized specimen. Maternal blood was assayed for 8-isoprostane
      concentrations using an enzyme-linked immunosorbent assay and stratified as
      elevated (>or=75th percentile) or not elevated (<75th percentile). Odds ratios
      (ORs) for preeclampsia were calculated and stratified by periodontal disease and
      the level of 8-isoprostane concentration. RESULTS: A total of 34 (4.3%) of 791
      women developed preeclampsia. Women with an 8-isoprostane concentration >or=75th
      percentile at enrollment were more likely to develop preeclampsia compared to
      women with an 8-isoprostane concentration <75th percentile (38.2% versus 24.4%,
      respectively; P = 0.07; OR: 1.91; 95% confidence interval [CI]: 0.94 to 3.90).
      Among women with moderate/severe periodontal disease, an elevated 8-isoprostane
      concentration (>or=75th percentile) did not significantly increase the likelihood
      for preeclampsia (adjusted OR: 2.08; 95% CI: 0.65 to 6.60). CONCLUSIONS: Women
      with oxidative stress early in pregnancy, as measured by an 8-isoprostane
      concentration >or=75th percentile, were at an increased risk for developing
      preeclampsia. The presence of periodontal disease did not appear to modify this
      risk.

PMID- 20151803
TI  - Tooth loss in 776 treated periodontal patients.
AB  - BACKGROUND: The most common form of periodontitis is a variably progressive
      dynamic pathologic process that causes attachment loss, destroys the alveolar
      bone supporting a tooth, and terminates with tooth loss. We evaluated the loss of
      teeth of treated periodontal patients categorized by severity and risk. METHODS:
      Each of nine periodontists evaluated 100 consecutive periodontal maintenance
      patients. The disease severity and risk level were determined from data at the
      initial examination. The number of teeth lost was determined from data at the
      initial and maintenance visits. RESULTS: A stepwise regression analysis showed
      that disease (P = 0.0000478) and risk (P = 0.00129) scores predicted the mean
      tooth loss rate. The adjusted R(2) statistic was 88.56%. The ordinal logistic
      regression model showed that only the disease score (P <0.0005) was significantly
      associated with the probability of patients losing a specific number of teeth.
      CONCLUSIONS: Categorizing a patient by severity may be beneficial in the
      management of the periodontal patient. The disease score can be used to establish
      a criterion and target for care. For example, treatment can result in nearly no
      lost teeth when the severity is low, and this benefit is lost when the severity
      is high. The disease score provides an objective means to quickly determine
      severity. An increase in the disease score provides evidence that a new treatment
      plan is needed. Therefore, the effect of the routine use of the disease score
      could result in fewer patients with severe disease and reduce the number of teeth
      lost.

PMID- 20151805
TI  - Initial periodontal therapy reduced systemic and local 25-hydroxy vitamin D(3)
      and interleukin-1beta in patients with aggressive periodontitis.
AB  - BACKGROUND: 25-hydroxy vitamin D(3) is the major circulating metabolite of
      vitamin D. Elevated plasma 25-hydroxy vitamin D(3) levels were verified to be
      associated with generalized aggressive periodontitis (GAgP). In the present
      study, the influence of initial periodontal therapy on systemic and local levels
      of 25-hydroxy vitamin D(3) and three related elements (osteocalcin and
      interleukin-1beta and -6) in patients with GAgP was investigated. METHODS:
      Nineteen patients with GAgP were enrolled. All patients received initial
      periodontal therapy. Gingival crevicular fluid at two sites of each subject were
      obtained before therapy and 2 and 6 months after therapy. Plasma was obtained
      before and 2 months after therapy from 12 of 19 subjects. Systemic and local
      levels of 25-hydroxy vitamin D(3), osteocalcin, and interleukin-1beta and -6
      before and after therapy were measured using radioimmunoassay or enzyme-linked
      immunosorbent assay kits and compared. RESULTS: The respective systemic 25
      hydroxy vitamin D(3) and interleukin-1beta levels significantly dropped from
      baseline to 2 months after therapy (29.28 nmol/l versus 22.50 nmol/l, P = 0.001,
      and 6.71 ng/l versus 3.23 ng/l, P <0.001, respectively). The respective local 25
      hydroxy vitamin D(3) and interleukin-1beta levels significantly decreased from
      baseline to 2 and 6 months after therapy (8,950 nmol/l versus 5,650 nmol/l versus
      3,438 nmol/l, P <0.001, and 10,595 ng/l versus 5,495 ng/l versus 3,960 ng/l, P
      <0.001, respectively). Systemic and local 25-hydroxy vitamin D(3) concentrations
      were positively correlated at baseline (r = 0.877; P = 0.022), as was osteocalcin
      (r = 0.939; P = 0.005). CONCLUSIONS: 25-hydroxy vitamin D(3) and interleukin
      1beta levels were systemically and locally reduced in patients with GAgP by
      initial periodontal therapy. 25-hydroxy vitamin D(3) might be involved in
      periodontal inflammation.

PMID- 20151806
TI  - Chemokine monocyte chemoattractant protein-3 in progressive periodontal lesions
      in patients with chronic periodontitis.
AB  - BACKGROUND: Chemokines are central in the activation and direction of leukocyte
      subsets to target tissues. However, the monocyte chemoattractant protein-3 (MCP
      3) has not been associated with chronic periodontitis. Chronic periodontitis is
      an infection showing episodic supporting tissue destruction. The aim of this
      study is to determine the levels and expression of MCP-3 in periodontal sites
      characterized by active periodontal connective tissue destruction. METHODS: The
      study population consisted of 15 patients with a progression of periodontitis (15
      of 56 patients), 18 patients with chronic periodontitis, and 10 healthy subjects
      without periodontal disease. As determined by the tolerance method, the 15
      patients with moderate to advanced chronic periodontitis showed a progression of
      periodontitis over a 4-month period. Periodontitis was characterized by at least
      six sites with a probing depth >or=5 mm, clinical attachment level >or=3 mm, and
      radiographic bone loss. Gingival crevicular fluid was collected using a paper
      strip. The total protein concentration was determined. An enzyme-linked
      immunosorbent assay was performed to determine the total amount of MCP-3, and an
      immunoWestern blot was conducted to assess molecular MCP-3 forms. To determine
      the MCP-3 expression by immunohistochemistry, gingival biopsies were obtained
      from patients with chronic periodontitis and healthy subjects during third-molar
      extraction surgery. Statistical analyses were performed using statistical
      software. Data were expressed as subject means +/- SD, using the chi(2) and
      Student t tests. RESULTS: The total amount and concentration of chemokine MCP-3
      were significantly higher in patients with chronic periodontitis than in healthy
      subjects (8.25 pg versus 0.53 pg, P = 0.006 and 2.95 pg/microl versus 0.45
      pg/microl, P = 0.04, respectively). Active sites showed a significantly higher
      total amount and concentration of MCP-3 than inactive sites (11.12 versus 2.88
      pg, P value = 0.005 and 3.95 versus 1.02, P value = 0.005, respectively). Western
      blot and immunohistochemical staining confirmed the presence of MCP-3 in
      periodontal disease, with observable differences between patients with chronic
      periodontitis and healthy subjects. CONCLUSIONS: MCP-3 was highly expressed in
      patients with chronic periodontitis, particularly in those with progressive
      periodontal lesions. MCP-3 could be involved in the recruitment of inflammatory
      cells toward periodontal tissues during the progression of the disease.

PMID- 20151802
TI  - Distance between external cortical bone and mandibular canal for harvesting ramus
      graft: a human cadaver study.
AB  - BACKGROUND: The aims of this study are to determine the distance of the external
      surface of the buccal cortical plate to the inferior alveolar canal in the
      mandibular molar region and to propose a safe thickness for harvesting a
      mandibular ramus block graft. METHODS: Thirty-four cadavers consisting of 26
      dentate jaws and eight jaws in the edentulous molar region were used in this
      study. All mandibular ramus grafts were harvested by one investigator with the
      grafts extending from the external oblique ridge (EOR) and 15 mm inferiorly in
      the apico-coronal direction and extending from the mid-buccal aspect of the first
      molar to the mid-buccal aspect of the third molar in the mesio-distal direction.
      Measurements were made of the cortical bone thickness of the harvested ramus
      graft and from the cemento-enamel junction (CEJ) to the EOR, the CEJ to the
      mandibular border, and the CEJ to the inferior alveolar nerve (IAN). RESULTS: The
      average buccal cortical plate thickness in dentate mandibles was 2.76 +/- 0.13
      mm, whereas in edentulous posterior mandibles it was 2.52 +/- 0.32 mm. The IANs
      were exposed in all jaws but were intact. CONCLUSION: The safe thickness to
      harvest ramus grafts was determined to be 2.5 to 3.0 mm.

PMID- 20151807
TI  - Salivary and gingival crevicular fluid melatonin in periodontal health and
      disease.
AB  - BACKGROUND: Melatonin, with its antioxidant properties, plays a pertinent role in
      influencing the pathogenesis of periodontal disease. This study aims to detect
      the presence of melatonin in gingival crevicular fluid (GCF) and to assess the
      levels of salivary and GCF melatonin in periodontal disease and show the
      correlation between salivary and GCF melatonin. METHODS: Forty-five subjects,
      based on the gingival and Russell periodontal indexes, were grouped as 15 healthy
      subjects (group 1), 15 subjects with gingivitis (group 2), and 15 subjects with
      periodontitis (group 3). Saliva and GCF samples were collected from all subjects.
      Melatonin levels were assessed using an enzyme-linked immunosorbent assay. The
      paired-sample test was used to correlate between saliva and GCF. RESULTS:
      Melatonin was present in GCF (mean: 1.54 pg/ml) with significantly less
      concentration compared to that of saliva (mean: 2.17 pg/ml). Salivary and GCF
      melatonin levels were reduced to the lowest concentrations in patients with
      chronic periodontitis (salivary melatonin: 0.07 pg/ml; GCF melatonin: 0.06 pg/ml;
      P <0.05), which were inversely proportional to the clinical indices. There was no
      significant correlation between salivary and GCF melatonin levels (P >0.05).
      CONCLUSIONS: Melatonin was expressed in GCF. Salivary and GCF melatonin levels
      varied from clinically healthy subjects (group 1) to subjects with periodontitis
      (group 3). Both salivary and GCF melatonin levels decreased in group 3 subjects
      compared to group 1 subjects, indicating that melatonin may have a protective
      role against periodontal disease, although further research is required to
      validate this hypothesis.

PMID- 20151808
TI  - Evaluation of gingival crevicular fluid adrenomedullin and human neutrophil
      peptide 1-3 levels of patients with different periodontal diseases.
AB  - BACKGROUND: Antimicrobial peptides participating in the innate host response are
      important contributors for maintaining the balance between health and disease.
      The aim of the present study is to investigate the levels of gingival crevicular
      fluid (GCF) adrenomedullin and human neutrophil peptides 1 through 3 (HNP1-3) in
      patients with different periodontal diseases. METHODS: A total of 77 subjects,
      including 20 patients with chronic periodontitis, 18 patients with generalized
      aggressive periodontitis, 20 patients with gingivitis, and 19 healthy subjects,
      were included in the present study. The probing depth, clinical attachment level,
      plaque index, and papilla bleeding index were assessed in all study subjects. GCF
      samples were analyzed for evaluating adrenomedullin and HNP1-3 levels by enzyme
      linked immunosorbent assay. RESULTS: The present study demonstrated that the
      periodontitis groups had a significantly higher total amount of GCF
      adrenomedullin compared to the gingivitis and healthy control groups after
      adjusting for age and gender (P <0.05). Additionally, GCF adrenomedullin levels
      were positively correlated with clinical periodontal parameters of sampling sites
      (P <0.05). The total amount of GCF HNP1-3 was not different among the study
      groups, and there was no correlation between the total amount of GCF HNP1-3 and
      clinical periodontal parameters (P >0.05). CONCLUSIONS: Our results suggest a
      defensive role for adrenomedullin during the host response in periodontal
      disease. Additionally, the lack of the HNP1-3 antimicrobial peptide might point
      to the deficiency of one of the protective mechanisms for periodontal tissues.

PMID- 20151801
TI  - Prevalence of peri-implantitis related to severity of the disease with different
      degrees of bone loss.
AB  - BACKGROUND: Several measurements are combined to diagnose peri-implant disease,
      and different thresholds are used to describe the disease. The purpose of this
      study was to evaluate the prevalence of peri-implant disease and to apply
      different diagnostic thresholds to assess its prevalence in relation to
      severities of peri-implantitis with different degrees of bone loss. METHODS: A
      total of 164 subjects with dental implants inserted at the Institute of Clinical
      Odontology, University of Oslo, between 1990 and 2005, were invited to join the
      project, and 109 subjects attended the examination (mean age: 43.8 years; range:
      18 to 80 years). The mean functional loading time was 8.4 years (SD: 4.6 years).
      The participants were examined clinically and radiographically. The following
      aspects of disease were assessed to describe the peri-implant condition:
      detectable radiographic peri-implant bone loss and inflammation, the presence of
      bleeding on probing at a probing depth >or=4 or >or=6 mm, and radiographic peri
      implant bone loss assessed at >or=2.0 and >or=3.0 mm. RESULTS: Assessing peri
      implantitis at different levels of severity yielded a substantial variance in
      prevalence (11.3% to 47.1%) in the present study population. CONCLUSION: Peri
      implant inflammation was a frequent finding with and without peri-implant bone
      loss.

PMID- 20151809
TI  - Antimicrobial susceptibility of moxifloxacin against gram-negative enteric rods
      from colombian patients with chronic periodontitis.
AB  - BACKGROUND: Gram-negative enteric rods were associated with periodontal diseases
      in several populations. The association between enteric and putative periodontal
      pathogens has received little attention in the literature. The present
      investigation determined the occurrence and in vitro antimicrobial susceptibility
      of isolates of Gram-negative enteric rods from Colombian patients with chronic
      periodontitis. METHODS: Clinical parameters and the in vitro antimicrobial
      sensitivity of isolates of Gram-negative enteric rods were examined in 76
      patients with chronic periodontitis in Medellin, Colombia. Subgingival samples
      were processed using culture and biochemical tests for the detection of
      periodontal and superinfecting pathogens. Selected colonies of Gram-negative
      enteric rods from pure cultures were used to test the susceptibility to
      amoxicillin/clavulanic acid, ciprofloxacin, and moxifloxacin. Chi-square and Mann
      Whitney tests were used to determine differences in clinical variables versus the
      presence or absence of Gram-negative enteric rods. RESULTS: Klebsiella pneumoniae
      was found in 12 patients, Pseudomonas aeruginosa was found in four patients, and
      three other species were recovered with a lower prevalence. Men (38.75%) tended
      to harbor more of the studied organisms than women (17.7%) (P = 0.04). Gram
      negative enteric rods in periodontal pockets correlated positively with the
      presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus
      actinomycetemcomitans), Porphyromonas gingivalis, and Prevotella
      intermedia/nigrescens (respectively, r = 0.66, 0.31, and 0.32; P <0.001). All
      superinfecting organisms demonstrated a high susceptibility to moxifloxacin and
      ciprofloxacin but exhibited a variable susceptibility to amoxicillin/clavulanic
      acid. CONCLUSIONS: This study found high levels of Gram-negative enteric rods in
      patients with chronic periodontitis. Moxifloxacin and ciprofloxacin appeared
      capable of eradicating these organisms from periodontal pockets. Its good
      activity against Gram-negative enteric rods and periodontopathogens suggests the
      potential use of moxifloxacin as an adjunctive antibiotic in the treatment of
      mixed periodontal infections.

PMID- 20151811
TI  - Differential production of macrophage inflammatory protein-1alpha, stromal
      derived factor-1, and IL-6 by human cultured periodontal ligament and gingival
      fibroblasts challenged with lipopolysaccharide from P. gingivalis.
AB  - BACKGROUND: Fibroblasts are considered important cells in periodontitis. When
      challenged by different agents, they respond through the release of cytokines
      that participate in the inflammatory process. The aim of this study is to
      evaluate and compare the expression and production of macrophage inflammatory
      protein (MIP)-1alpha, stromal-derived factor (SDF)-1, and interleukin (IL)-6 by
      human cultured periodontal ligament and gingival fibroblasts challenged with
      lipopolysaccharide (LPS) from Porphyromonas gingivalis. METHODS: Fibroblasts were
      cultured from biopsies of gingival tissue and periodontal ligament of the same
      donors and used on the fourth passage. After confluence in 24-well plates, the
      culture medium alone (control) or with 0.1 to 10 microg/ml of LPS from P.
      gingivalis was added to the wells, and after 1, 6, and 24 hours, the supernatant
      and the cells were collected and analyzed by enzyme-linked immunosorbent assay
      and real-time polymerase chain reaction, respectively. RESULTS: MIP-1alpha, SDF
      1, and IL-6 protein production was significantly greater in gingival fibroblasts
      compared to periodontal ligament fibroblasts. IL-6 was upregulated in a time
      dependent manner, mainly in gingival fibroblasts (P <0.05), which secreted more
      MIP-1alpha in the lowest concentration of LPS used (0.1 microg/ml). In contrast,
      a basal production of SDF-1 that was inhibited with the increase of LPS
      concentration was detected, especially after 24 hours (P <0.05). CONCLUSION: The
      distinct ability of the gingival and periodontal ligament fibroblasts to secrete
      MIP-1alpha, SDF-1, and IL-6 emphasizes that these cells may differently
      contribute to the balance of cytokines in the LPS-challenged periodontium.

PMID- 20151812
TI  - Factors influencing the presence of interproximal dental papillae between
      maxillary anterior teeth.
AB  - BACKGROUND: The presence of interdental papillae in the maxillary anterior region
      plays a key esthetic role. The aim of this study is to investigate the impact of
      demographic variables, such as gender and ages, and radiographic measurements of
      interdental area anatomy on the presence of interdental papillae. METHODS:
      Periapical radiographs of 102 interdental papillae between maxillary anterior
      teeth were obtained in 30 adults who had fully erupted permanent dentition,
      healthy gingiva, and well-aligned maxillary anterior teeth. A radiopaque material
      was placed on the tip of the interdental papilla and the mucogingival junction.
      Radiographic measurements of tooth shape, alveolar bone level, and interdental
      space anatomy were undertaken using computer software. RESULTS: When each factor
      was evaluated individually, the shorter the distance between the contact bone and
      alveolar bone crest, the shorter the distance between two adjacent teeth, and the
      smaller the embrasure area, the more likely interdental papillae were present.
      Interdental papillae were more likely to be present between teeth with a
      rectangular tooth form. When all factors were evaluated together, the presence of
      interdental papillae was only significantly related to the distance from the
      contact point to the bone crest (P = 0.038). CONCLUSION: In the anterior
      maxillary region, the shorter the distance between the contact point to the bone
      crest, the more likely interdental papillae were present.

PMID- 20151816
TI  - MEFV gene mutations in Egyptian patients with familial Mediterranean fever.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disorder
      characterized by recurrent attacks of fever and serositis. The disease affects
      mainly Mediterranean populations and is caused by mutations in the MEFV gene.
      AIM: This work was carried out to identify and determine the frequencies of MEFV
      gene mutations in Egyptian patients in whom FMF was diagnosed. METHODS: We
      investigated 316 patients with a clinical diagnosis of FMF for 12 MEFV mutations
      including the 5 most common known mutations M694V, V726A, M694I, M680I, and E148Q
      by allele-specific hybridization. RESULTS: Mutations were detected in 182 (57.6%)
      patients: 20 were homozygous, 80 were compound heterozygous, and 82 had only one
      identifiable mutant allele. In patients with clinically definite FMF (n = 112),
      no mutations were detected in 28 patients; whereas in patients with clinically
      unlikely FMF (n = 48), genetic analysis established the diagnosis in 6 patients.
      Overall, 10 mutations were detected in our patients. The most common were M694I
      (34%), E148Q (22.7%), V726A (15.6%), M680I (12.1%), and M694V (7.8%). M694V was
      observed in severe disease and in patients with amyloidosis. CONCLUSION: We were
      able to identify a wide spectrum of MEFV mutations in Egyptian patients in whom
      FMF was diagnosed. Frequencies of individual mutations showed some differences
      from those in other Mediterranean populations.

PMID- 20151815
TI  - Process-Induced Cell Injury in Laser Direct Writing of Human Colon Cancer Cells.
AB  - Matrix-assisted pulsed-laser evaporation direct-write has emerged as a promising
      technique for biological construct fabrication. The posttransfer cell viability
      in matrix-assisted pulsed-laser evaporation direct-write depends on various
      operating conditions such as the applied laser fluence. To date, the effects of
      operating conditions such as laser fluence, direct-writing height, and cell
      density on the posttransfer cell viability have not been well elucidated. This
      study investigates the effects of operating conditions on the posttransfer cell
      viability in laser direct writing of human colon cancer HT-29 cells. It has been
      observed that (1) the HT-29 cell viability decreases from 95% to 78% as the laser
      fluence increases from 258 to 1482 mJ/cm(2), and the posttransfer cell
      proliferation capacity does not vary significantly as the laser fluence changes;
      (2) the direct-writing height does not have noticeable effect on the posttransfer
      cell viability under low laser fluences (258 and 869 mJ/cm(2)). However, a larger
      height (such as 29.3 mm) led to an almost 8% viability improvement compared with
      that of 16.6 mm under a high laser fluence (1482 mJ/cm(2)); and (3) the
      posttransfer cell viability is not dependent on the cell density for a range from
      1 * 10(6) to 1 * 10(7) cells/mL.

PMID- 20151813
TI  - Clinical and histologic evaluation of granular Beta-tricalcium phosphate for the
      treatment of human intrabony periodontal defects: a report on five cases.
AB  - BACKGROUND: The aim of the study is to clinically and histologically evaluate the
      healing of advanced intrabony defects treated with open flap debridement and the
      adjunct implantation of granular beta tricalcium phosphate (beta-TCP). METHODS:
      Five patients, each displaying advanced combined 1- and 2-wall intrabony defects
      around teeth scheduled for extraction or root resection, were recruited.
      Approximately 6 months after surgery, the teeth or roots were removed together
      with a portion of their surrounding soft and hard tissues and processed for
      histologic evaluation. RESULTS: The mean probing depth (PD) was reduced from 10.8
      +/- 2.3 mm presurgically to 4.6 +/- 2.1 mm, whereas a mean clinical attachment
      level (CAL) gain of 5.0 +/- 0.7 mm was observed. The increase in gingival
      recession was 1.2 +/- 3.2 mm. The histologic evaluation indicated the formation
      of new cellular cementum with inserting collagen fibers to a varying extent
      (mean: 1.9 +/- 0.7 mm; range: 1.2 to 3.03 mm) coronal to the most apical extent
      of the root instrumentation. The mean new bone formation was 1.0 +/- 0.7 mm
      (range: 0.0 to 1.9 mm). In most specimens, beta-TCP particles were embedded in
      the connective tissue, whereas the formation of a mineralized bone-like or
      cementum-like tissue around the particles was only occasionally observed.
      CONCLUSION: The present data indicates that treatment of intrabony periodontal
      defects with this beta-TCP may result in substantial clinical improvements such
      as PD reduction and CAL gain, but this beta-TCP does not seem to enhance the
      regeneration of cementum, periodontal ligament, and bone.

PMID- 20151804
TI  - Association of gingival crevicular fluid biomarkers during periodontal
      maintenance with subsequent progressive periodontitis.
AB  - BACKGROUND: The analysis of biomarkers in gingival crevicular fluid (GCF) may be
      helpful in forecasting patient vulnerability to future attachment loss. The
      purpose of this study is to correlate GCF biomarkers of inflammation and bone
      resorption with subsequent periodontal attachment and bone loss in a longitudinal
      trial of a matrix metalloproteinase (MMP) inhibitor. METHODS: GCF was collected
      from two periodontal pockets (mean +/- SD: 5.1 +/- 1.0 mm) at baseline and
      annually in postmenopausal females with moderate to advanced periodontitis
      undergoing periodontal maintenance every 3 to 4 months during a 2-year double
      masked, placebo-controlled, randomized clinical trial of subantimicrobial dose
      doxycycline (SDD; 20 mg two times a day). Subjects were randomized to SDD (n =
      64) or a placebo (n = 64). GCF was analyzed for the inflammation markers
      interleukin (IL)-1beta (using enzyme-linked immunosorbent assay), total
      collagenase activity (using hydrolysis of a synthetic octapeptide), and MMP-8
      (using a Western blot) and the bone-resorption marker carboxyterminal telopeptide
      cross-link fragment of type I collagen (ICTP) (using a radioimmunoassay).
      Generalized estimating equations were used to associate these biomarkers,
      categorized into tertiles, with subsequent clinical attachment (using an
      automated disk probe) or interproximal bone loss (using radiography). Odds ratio
      (OR) values compared highest to lowest tertile groups. RESULTS: Increases in GCF
      IL-1beta and MMP-8 during the first year of periodontal maintenance were
      associated with increased odds of subsequent (year 2) periodontal attachment loss
      (OR = 1.67; P = 0.01 and OR = 1.50; P = 0.02, respectively) driven by the placebo
      group. Elevated baseline ICTP was also associated with increased odds of 1- and 2
      year loss of alveolar bone density (OR = 1.98; P = 0.0001) in the placebo group,
      not the SDD group, and a loss of bone height (OR = 1.38; P = 0.06), again driven
      by the placebo group. CONCLUSION: These data support the hypothesis that elevated
      GCF biomarkers of inflammation and bone resorption from a small number of
      moderate/deep sites have the potential to identify patients who are vulnerable to
      progressive periodontitis, and SDD may modify that risk.

PMID- 20151810
TI  - Characterization of mandibular bone in a mouse model of chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a worldwide health problem with
      increasing prevalence and poor outcomes, including severe cardiovascular disease
      and renal osteodystrophy. With advances in medical treatment, patients with CKD
      are living longer and require oral care. The aim of this study is to determine
      the effects of CKD and dietary phosphate on mandibular bone structure using a
      uremic mouse model. METHODS: Uremia (U) was induced in female dilute brown
      agouti/2 mice by partial renal ablation. Uremic mice received a normal-phosphate
      (NP) or a high-phosphate (HP) diet. sham surgeries were performed in a control
      group of mice; half received an NP diet, and the other half was fed an HP diet.
      At termination, animals were sacrificed, and mandibles were collected for
      microcomputed tomography (micro-CT) and histologic analysis. RESULTS: Sera levels
      of blood urea nitrogen, parathyroid hormone, and alkaline phosphatase were
      significantly increased in U/NP and U/HP mice versus sham controls, whereas serum
      calcium was increased in the U/HP group, and no differences were noted in serum
      phosphate levels among groups. Micro-CT analyses revealed a significant reduction
      in cortical bone thickness and an increase in trabecular thickness and trabecular
      bone volume/tissue volume in U/NP and U/HP groups compared to the sham/NP group.
      A significant reduction in cortical bone thickness was also found in the sham/HP
      group versus the sham/NP group. Histologic evaluation confirmed increased
      trabeculation in the U groups. CONCLUSION: CKD in mice, especially under
      conditions of HP feeding, results in marked effects on alveolar bone homeostasis.

PMID- 20151818
TI  - Testing the carotenoid trade-off hypothesis in the polychromatic Midas cichlid,
      Amphilophus citrinellus.
AB  - Many animals use carotenoid pigments derived from their diet for coloration and
      immunity. The carotenoid trade-off hypothesis predicts that, under conditions of
      carotenoid scarcity, individuals may be forced to allocate limited carotenoids to
      either coloration or immunity. In polychromatic species, the pattern of
      allocation may differ among individuals. We tested the carotenoid trade-off
      hypothesis in the Midas cichlid, Amphilophus citrinellus, a species with two
      ontogenetic color morphs, barred and gold, the latter of which is the result of
      carotenoid expression. We performed a diet-supplementation experiment in which
      cichlids of both color morphs were assigned to one of two diet treatments that
      differed only in carotenoid content (beta-carotene, lutein, and zeaxanthin). We
      measured integument color using spectrometry, quantified carotenoid
      concentrations in tissue and plasma, and assessed innate immunity using lysozyme
      activity and alternative complement pathway assays. In both color morphs, dietary
      carotenoid supplementation elevated plasma carotenoid circulation but failed to
      affect skin coloration. Consistent with observable differences in integument
      coloration, we found that gold fish sequestered more carotenoids in skin tissue
      than barred fish, but barred fish had higher concentrations of carotenoids in
      plasma than gold fish. Neither measure of innate immunity differed between gold
      and barred fish, or as a function of dietary carotenoid supplementation. Lysozyme
      activity, but not complement activity, was strongly affected by body condition.
      Our data show that a diet low in carotenoids is sufficient to maintain both
      coloration and innate immunity in Midas cichlids. Our data also suggest that the
      developmental transition from the barred to gold morph is not accompanied by a
      decrease in innate immunity in this species.

PMID- 20151817
TI  - The relationship of metabolic performance and distribution in black-capped and
      Carolina chickadees.
AB  - In endotherms, metabolic performance is associated with a wide array of
      ecological traits, including species distribution. Researchers have suggested
      that the northern boundaries of North American passerines are limited by their
      ability to sustain the high metabolic rates required for thermoregulation. Black
      capped chickadees (Poecile atricapillus; BC) are year-round residents in most of
      Canada and the northern half of the United States, whereas Carolina chickadees
      (Poecile carolinensis; CA) are found exclusively in the southeastern United
      States. These species hybridize along a narrow contact zone that has been moving
      northward at a rate of about 1.6 km per decade, coincident with warming
      temperatures in Ohio. The location of the chickadee hybrid zone in Ohio closely
      matches air temperature isotherms, further suggesting that metabolic rate may
      correlate with distribution in these species. We tested the hypothesis that
      distribution patterns of chickadees are linked with their rate of metabolism. For
      populations of BC and CA chickadees, we measured basal metabolic rates (BMRs) and
      cold-induced peak metabolic rates from areas that differ in winter temperatures
      and supplemented this information with data from other studies. Although our
      findings suggest a general relationship between lower air temperatures and higher
      metabolic rate among black-capped chickadee populations, this trend was not
      robust across all locations. There was no significant relationship between lower
      air temperatures and metabolism in Carolina chickadees. Within Ohio, hybrids had
      a significantly higher mass-corrected BMR than either parental species. We
      suggest that the mtDNA-nDNA mismatch of hybrids may produce less efficient
      mitochondrial protein complexes, which in turn affects the efficiency of ATP
      production, thereby increasing rate of oxygen consumption to meet ATP demands.

PMID- 20151820
TI  - Assays for thyroid-stimulating hormone receptor antibodies employing different
      ligands and ligand partners may have similar sensitivity and specificity but are
      not interchangeable.
AB  - BACKGROUND: The best biochemical marker of Graves' disease (GD) is the presence
      in serum of autoantibodies to the thyroid-stimulating hormone receptor (hTSHR
      Ab). The aim of this study was to evaluate the performances of two sensitive
      hTSHR-Ab assays with a specific focus on the clinical importance of differences
      in results. Both assays are competitive in nature but employ quite different
      types of ligands. In the "M22-pTSHR" assay, hTSHR-Ab competes with a labeled
      monoclonal antibody (M22*) against the thyrotropin (TSH)-receptor for binding to
      porcine TSH receptors. In the "bTSH-rhTSHR" assay, hTSHR-Ab competes with labeled
      bovine TSH for binding to recombinant human TSH receptors. METHODS: bTSH-rhTSHR
      and M22-pTSHR were measured in patients from a population study: 106 had new
      hyperthyroidism due to GD, 93 had multinodular toxic goiter, 100 had new primary
      autoimmune hypothyroidism, and 100 were healthy controls. RESULTS: Receiver
      operating characteristic curves indicated a high sensitivity and specificity of
      both assays (area under curve, bTSH-rhTSHR: 0.977 [confidence interval: 0.954
      1.00]; M22-pTSHR: 0.979 [confidence interval: 0.957-1.00]). The two assays
      identified nearly the same patients who were hTSHR-Ab positive, though large
      differences in hTSHR-Ab values were obtained in a number of individual patients
      (ratio bTSH-rhTSHR/M22-pTSHR, range: 0.33-6.5 in patients positive with both
      assays). Values were in average 2.5 times higher with the bTSH-rhTSHR assay
      compared with the M22-pTSHR assay, corresponding to the difference in recommended
      clinical cut-off values (1.0 IU/L and 0.4 u/L). The bTSH-rhTSHR assay had a
      considerably lower intraassay coefficients of variation of 3.8%; for M22-pTSHR,
      it was 9.5% (p < 0.01). CONCLUSIONS: Both assays had a high sensitivity and
      specificity for diagnosing GD. hTSHR-Ab values were in average 2.5 times higher
      with the bTSH-rhTSHR assay compared with the M22-pTSHR assay. In individual
      patients, the ratio between results obtained using the two assays varied widely.
      Thus, results obtained using one assay cannot be quantitatively transformed to
      values obtained using the other assay. bTSH-rhTSHR had a considerably lower
      intraassay coefficients of variation and it may be better suited for longitudinal
      studies of hTSHR-Ab.

PMID- 20151821
TI  - Benefits of thyrotropin suppression versus the risks of adverse effects in
      differentiated thyroid cancer.
AB  - BACKGROUND: Despite clinical practice guidelines for the management of
      differentiated thyroid cancer (DTC), there are no recommendations on the optimal
      serum thyrotropin (TSH) concentration to reduce tumor recurrences and improve
      survival, while ensuring an optimal quality of life with minimal adverse effects.
      The aim of this review was to provide a risk-adapted management scheme for
      levothyroxine (L-T4) therapy in patients with DTC. The objective was to establish
      which patients require complete suppression of serum TSH levels, given their risk
      of recurrent or metastatic DTC, and how potential adverse effects on the heart
      and skeleton, induced by subclinical hyperthyroidism, in concert with advanced
      age and comorbidities, may influence the degree of TSH suppression. SUMMARY: A
      risk-stratified approach to predict the rate of recurrence and death from thyroid
      cancer was based on the recently revised American Thyroid Association guidelines.
      A stratified approach to predict the risk from the adverse effects of L-T4 was
      devised, taking into account the age of the patient, as well as the presence of
      preexisting cardiovascular and skeletal risk factors that might predispose to the
      development of long-term adverse cardiovascular or skeletal outcomes,
      particularly increased heart rate and left ventricular mass, atrial fibrillation,
      and osteoporosis. Nine potential patient categories can be defined, with
      differing TSH targets for both initial and long-term L-T4 therapy. CONCLUSION:
      Before deciding on the degree of TSH suppression during initial and long-term L
      T4 treatment in patients with DTC, it is necessary to consider the aggressiveness
      of DTC, as well as the potential for adverse effects induced by iatrogenic
      subclinical hyperthyroidism. More aggressive TSH suppression is indicated in
      patients with high-risk disease or recurrent tumor, whereas less aggressive TSH
      suppression is reasonable in low-risk patients. In patients with high-risk DTC
      and an equally high risk of adverse effects, long-term treatment with L-T4
      therapy should be individualized and balanced against the potential for adverse
      effects. In patients with an intermediate risk for thyroid cancer recurrence and
      a high risk of adverse effects of therapy, the degree of TSH suppression should
      be reevaluated during the follow-up period. Normalization of serum TSH is
      advisable for long-term treatment of disease-free elderly patients with DTC and
      significant comorbidities.

PMID- 20151822
TI  - Tall-cell variant of papillary thyroid carcinoma: a matched-pair analysis of
      survival.
AB  - BACKGROUND: The tall-cell variant (TCV) of papillary thyroid carcinoma (PTC) is
      considered a more aggressive variant of PTC, with a poor prognosis. This is
      largely due to the tendency for TCV to present at an older age and with
      extrathyroidal extension (ETE). When these two variables are controlled for, it
      is unclear whether tall-cell histology alone portends a poor prognosis. Because
      previous studies have been underpowered to adequately answer this question, we
      hypothesized that TCV may have poorer prognosis than PTC. Our objective was to
      utilize a large cancer registry to obtain sufficient power to differentiate
      between outcomes in cases of TCV and PTC. METHODS: Using the National Cancer
      Institute's Surveillance, Epidemiology, and End Results database, we identified
      278 TCV patients and 2522 classical PTC patients with sufficient information for
      a detailed matched-pair analysis. Each TCV patient was matched with a PTC patient
      for age, sex, extent of ETE, regional and distant metastases, surgical and
      adjuvant therapy, and year of diagnosis. The TCV cohort was then compared against
      all PTC cases and matched PTC cases. RESULTS: Compared with classical PTC, TCV
      patients presented at an older age (54.3 years vs. 46.3 years, p < 0.0001) had a
      higher rate of ETE (53.6% vs. 30.2%, p < 0.0001) and poorer 5-year disease
      specific survival (81.9% vs. 97.8%, p < 0.0001). In the matched-pair analysis
      comparing TCV patients to the matched PTC cohort, 5-year disease-specific
      survival was poorer in the TCV cohort (81.9% vs. 91.3%, p = 0.049). The number of
      deaths in the TCV cohort was higher than in the matched PTC cohort (p = 0.043).
      CONCLUSIONS: TCV exhibits poorer survival than classical PTC. When the major
      prognostic factors for thyroid cancer are controlled for, including age and ETE,
      tall-cell histology alone remains a significant prognostic factor for disease
      specific death.

PMID- 20151819
TI  - Resveratrol, thyroid cancer, and iodide: drink up?

PMID- 20151823
TI  - Changes of apoptosis, p53, and bcl-2 by irradiation in poorly differentiated
      thyroid carcinoma cell lines: a prognostic marker for the prospect of therapeutic
      success?
AB  - BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) has an unfavorable
      prognosis. Surgical management is the principal treatment approach. In addition,
      radioiodine treatment and external beam radiotherapy (EBRT) are given to reduce
      the risk of local relapse. Despite aggressive therapy, the response to treatment
      tends to become increasingly poorer over time. The objective of this study was to
      investigate the induction of apoptosis by EBRT as a function of p53 and bcl-2
      protein levels in PDTC. The predictive value of these molecules with respect to
      treatment efficacy was evaluated. MATERIALS AND METHODS: Two different cell lines
      of PDTC (FTC-133 and ML-1) were irradiated with a dose of 30 Gy. Apoptotic cells
      were quantified using terminal deoxynucleotidyltransferase-dUTP nick-end labeling
      staining without irradiation, 48 and 96 hours after irradiation. The protein
      levels of p53 and bcl-2 were measured simultaneously using flow cytometry and
      western blotting. The cell cycle distribution was determined. RESULTS: Untreated
      FTC-133 cells showed a high rate of apoptosis, a high protein level of p53, and a
      low bcl-2 protein level. Forty-eight hours after irradiation, a slight reduction
      in apoptotic cells was observed in conjunction with an increase in bcl-2 and p53
      protein levels. The slightly reduced fraction of apoptotic cells remained at the
      same level up to 96 hours after irradiation, whereas the p53 protein level was
      further downregulated. The cell cycle distribution showed a significant G2/M
      arrest after 48 hours and recovery 96 hours after irradiation. ML-1 cells did not
      show any detectable p53 levels and revealed a low rate of apoptosis which
      significantly increased 48 hours after irradiation. Ninety-six hours after
      irradiation, a decrease in apoptosis was detectable. The protein level of bcl-2
      increased significantly within 48 hours and decreased 96 hours after irradiation.
      The cell cycle distribution showed a G2/M arrest after 48 hours without a
      recovery 96 hours after irradiation. CONCLUSIONS: The p53 and bcl-2 expression
      profiles and the observed apoptotic rates of FTC-133 and ML-1 under irradiation
      are consistent with a more aggressive FTC-133 phenotype. Alterations in p53- and
      bcl-2 protein levels yield predictive information for EBRT efficacy.

PMID- 20151824
TI  - Quality of life and effectiveness comparisons of thyroxine withdrawal,
      triiodothyronine withdrawal, and recombinant thyroid-stimulating hormone
      administration for low-dose radioiodine remnant ablation of differentiated
      thyroid carcinoma.
AB  - BACKGROUND: Few reports have examined the use of recombinant human thyroid
      stimulating hormone (rhTSH) for ablation of postsurgical thyroid remnants after
      low-dose radioactive iodine (RI) therapy, compared with conventional thyroid
      hormone withdrawal. We investigated whether patient preparation using rhTSH was
      comparable to conventional thyroid hormone withdrawal with respect to efficacy of
      postsurgical remnant ablation in low-risk patients receiving a 30 mCi RI. In
      addition, we also evaluated the impact of rhTSH (rhTSH vs. conventional thyroid
      hormone withdrawal) on quality of life (QoL) of thyroid cancer patients
      undergoing RI ablation. METHODS: This study included three groups of patients,
      enrolled consecutively. From February 2006 to March 2007, 291 patients were
      enrolled and randomized, after total thyroidectomy: (1) withdrawal of
      levothyroxine (LT4) for 4 weeks (T4-WD Group, n = 89), (2) withdrawal of LT4 for
      4 weeks plus 2 weeks on and then 2 weeks off liothyronine (LT3) (T3-WD Group, n =
      133), and (3) rhTSH administration (rhTSH Group, n = 69). QoL was determined at
      the time of ablation. RESULTS: Patients in the three groups did not differ
      significantly in baseline characteristics or tumor, node and metastasis (TNM)
      staging. In all study groups, serum TSH levels showed very good stimulation
      (mean, 82.24 +/- 18.21 mU/L), without significant between-group differences (p =
      0.5213). Follow-up examinations were performed 12 months after ablation to assess
      ablation outcome in each group by 131 whole body scans (WBSs), serum
      thyroglobulin measurement after TSH stimulation, and neck ultrasonography. The
      successful ablation rate was 91.0% in T4-WD Group, 91.7% in T3-WD Group, and
      91.3% in rhTSH Group, without significant between-preparation differences (p =
      0.2061). QoL was better preserved in rhTSH Group than in T4-WD and T3-WD Groups
      (p < 0.0001). However, there was no QoL difference at the time of ablation
      between T4-WD and T3-WD Groups. CONCLUSIONS: Our study indicates that use of
      rhTSH preserves QoL in patients undergoing RI ablation and affords an ablation
      success rate comparable to that seen after thyroid hormone withdrawal. Notably,
      ablation preparation using withdrawal of LT3 for 2 weeks did not prevent
      development of profound hypothyroidism, as also occurred when LT4 alone was
      withdrawn for 4 weeks.

PMID- 20151826
TI  - Thyroid function in term and late preterm infants with respiratory distress in
      relation to severity of illness.
AB  - BACKGROUND: Transient hypothyroxinemia is common in extremely premature infants,
      but has not been extensively investigated in ill term and late preterm infants.
      We hypothesized that free thyroxine (T(4)) levels in term and late preterm
      infants with respiratory distress would be inversely related to severity of
      illness METHODS: Eligible infants included those had > or =35 weeks of gestation
      requiring mechanical ventilation or nasal continuous positive airway pressure.
      Thyroid function (thyroid-stimulating hormone, T(4), free T(4) [fT(4)], and free
      triiodothyronine) and cortisol levels were collected at four specified intervals
      (birth, day 2, day 3, and day 5 of life). Illness severity was measured using
      score for neonatal acute physiology (SNAP). Infants with an SNAP > or =10 were
      considered to have severe illness. Statistical analysis included repeated
      measures analysis of variance. RESULTS: A total of 20 patients were enrolled in
      the study. The mean gestational age of study infants was 37.0 +/- 1.7 weeks.
      Infant with SNAP > or =10 had a diminished thyroid-stimulating hormone at birth.
      There was an inverse correlation between SNAP at birth and fT(4.) There was also
      an inverse correlation between lowest measured fT(4) and highest mean airway
      pressure, oxygenation index, and A-a gradient. Infants who received inhaled
      nitric oxide had diminished fT(4) levels compared to infants who did not receive
      this therapy. There were no differences in cortisol in those infants with and
      without SNAP > or =10 during the study period. CONCLUSIONS: In our study sample,
      there was an association between severity of illness and fT(4) levels at birth,
      and infants requiring inhaled nitric oxide showed decreased fT(4) over the study
      time. Further research is warranted to determine whether T(4) supplementation
      would be beneficial in term and late preterm infants with respiratory distress.

PMID- 20151829
TI  - Charcoal hemoperfusion in the treatment of levothyroxine intoxication.
AB  - BACKGROUND: Levothyroxine (l-thyroxine) intoxication may arise from intentional
      or accidental ingestion of excessive doses of the hormone and may cause symptoms
      equivalent to thyroid storm. We report a case of massive accidental l-thyroxine
      intoxication resulting from an error in the preparation of capsules to treat
      goiter. SUMMARY: A 61-year-old woman was admitted showing high levels of thyroid
      hormones, with serum-free l-thyroxine level of 955.90 nmol/L (74.1 ng/mL) (normal
      values: 11.61-27.09 nmol/L or 0.9-2.1 ng/mL). It was discovered that she had
      ingested 50 mg instead of 50 microg/day of l-thyroxine during 9 days. Following
      charcoal hemoperfusion, the levels of total thyroxine, serum-free l-thyroxine,
      and triiodothyronine declined dramatically, with a reproducible pattern of
      reduction in hormone levels observed after each of the three sessions. The
      patient recovered from her stuporous mental state, atrial fibrillation, and acute
      respiratory failure. CONCLUSION: The use of hemoperfusion with a charcoal filter
      appears to be a very important therapeutic tool for the treatment of acute and
      severe forms of thyrotoxicosis due to l-thyroxine intoxication.

PMID- 20151827
TI  - Resveratrol increases iodide trapping in the rat thyroid cell line FRTL-5.
AB  - BACKGROUND: Resveratrol, a polyphenol found in grapes, exhibits several
      beneficial health effects by its antioxidant, antiinflammatory, and
      chemopreventive properties. The aim of the present study was to determine the
      effect of resveratrol on iodide trapping and efflux as well as its mode of action
      using FRTL-5 cells, having in mind the pivotal role of the natrium iodide
      symporter (NIS) in the treatment of differentiated thyroid cancers. METHODS:
      Cells were treated with resveratrol for various times and doses, in the presence
      or absence of thyrotropin (TSH). Iodide trapping, iodide efflux, rat NIS (rNIS)
      protein expression, and cyclic AMP (cAMP) production were evaluated. RESULTS:
      Resveratrol increased iodide trapping in a time-dependent (optimal 6 hours) and
      dose-dependent (100 microM) way in the presence of TSH. It showed an additive
      effect when concomitantly added with an optimal dose of TSH. Resveratrol (50
      microM) increased (threefold) rNIS protein expression. In TSH-deprived cells,
      resveratrol also provoked an increase in rNIS protein (>3-fold in 6 hours) with
      an optimum at 40 microM. Resveratrol did not inhibit iodide efflux from FRTL-5
      cells. It neither increased intracellular cAMP nor induced the arborization of
      living cells, two TSH-induced effects. A non-cAMP mode of action is highly
      suspected. CONCLUSIONS: Resveratrol increases iodide trapping in FRTL-5 cells,
      increasing iodide influx and rNIS protein level even in the absence of TSH. It
      has an additive effect with TSH. Consequently, resveratrol could be a promising
      molecule for radioiodide therapy in follicular and papillary differentiated
      thyroid carcinoma in association with recombinant human TSH.

PMID- 20151828
TI  - Multiple thyroid cysts may be a cause of hypothyroidism in patients with
      relatively high iodine intake.
AB  - BACKGROUND: Multiple cysts of the thyroid gland have not been recognized as one
      of the causes of hypothyroidism. Here we present six patients from a region with
      relatively high iodine intake in whom multiple cysts of the thyroid were
      associated with hypothyroidism or the development of hypothyroidism. SUMMARY: All
      patients were women and ranged in age from 49 to 71. Their thyroids were mildly
      enlarged, tests for thyroid autoantibodies were negative, and multiple cysts were
      detected in the thyroid by ultrasonography. By dietary questionnaire their iodine
      intake was estimated to range from 2 to 10 mg of iodine daily. Otherwise, there
      was no evidence for disorders or factors associated with hypothyroidism. All four
      patients who agreed to dietary iodine restriction became euthyroid at
      approximately 1 month after a low-iodine diet (less than 0.5 mg iodine per day)
      was started. CONCLUSIONS: Although these patients were from a region with high
      iodine intake and had a relatively high intake compared with most regions of the
      world, this amount of iodine intake is not associated with hypothyroidism in
      otherwise healthy persons. Therefore, we propose that multiple thyroid cysts,
      which we have termed polycystic goiter, is probably a cause of hypothyroidism in
      patients with a relatively high iodine intake.

PMID- 20151825
TI  - Multidetector computed tomography in the preoperative evaluation of retrosternal
      goiters: a useful procedure for patients for whom magnetic resonance imaging is
      contraindicated.
AB  - BACKGROUND: Diagnostic imaging provides useful anatomical and morphological
      information of cervico-mediastinal goiters. The aim of this study was to assess
      the usefulness of multidetector computed tomography (MDCT) with multiplanar
      reformatting and volume rendering reconstructions for the preoperative evaluation
      of retrosternal goiters in patients for whom magnetic resonance imaging is
      contraindicated. METHODS: From March 2006 to January 2009, 34 patients (20 women
      and 14 men; mean age, 48 years; range, 42-74 years) with suspected cervico
      mediastinal goiter were assessed by MDCT after intravenous injection of contrast
      material. The following parameters were evaluated: morphology, size, and
      enhancement of thyroid lobes; presence, location, and mediastinal extension of
      thyroid tissue; and relations with mediastinal vessels and organs. All patients
      underwent thyroidectomy. A reference group of 34 patients evaluated by single
      detector computed tomography was created. The two groups of patients were
      compared searching for operative time (OT, in hours), hospital stay (HS, in
      days), and morbidity rate observed after thyroid surgery in all cases. RESULTS:
      In 29/34 patients, thyroid was enlarged with left mediastinal extension in 12
      cases, right extension in 10 cases, and posterior extension in 7 cases. In 3/34
      patients, a normal cervical thyroid connected to the mediastinal goiter through a
      thin parenchymal stripe was observed. In 2/34 patients, thyroid lobes were
      enlarged, without mediastinal extension. By comparing the two groups of patients
      for OT and HS values, a significant reduction to 3.7 +/- 0.1 hours and 4.3 +/-
      0.1 days, respectively, was found in the group of MDCT patients, and also a trend
      to the reduction for morbidity rate (21%) could be recognized. CONCLUSIONS: MDCT
      represents a noninvasive tool in the evaluation of retrosternal goiters. High
      quality multiplanar reformatting and volume rendering reconstructions allow an
      optimal analysis of the plunged gland and could reduce OT, HS, and probably the
      morbidity rate.

PMID- 20151830
TI  - Resistance to thyroid hormone in a patient with coexisting Graves' disease.
AB  - BACKGROUND: Resistance to thyroid hormone (RTH) is a rare disorder in which an
      abnormality in the binding domain of the thyroid hormone receptor results in end
      organ insensitivity to the actions of thyroid hormones. This disorder is
      sometimes misdiagnosed as Graves' disease due to the presence of a goiter with
      high Iodine-123 thyroid uptake and high levels of total and free thyroid
      hormones. Additionally, some patients with RTH may experience palpitations or
      tachycardia. There is a previous report of a patient with pituitary RTH and
      concurrent Graves' disease. SUMMARY: We describe a patient who was found to have
      a goiter with signs and symptoms of hyperthyroidism by his primary care
      physician. Work-up revealed a low thyroid stimulating hormone (TSH), high thyroid
      stimulating immunoglobulins, high Iodine-123 thyroid uptake, as well as increased
      homogenous activity in both thyroid glands on nuclear scan and a suppressed TSH.
      Diagnosis of Graves' disease was made, and the patient underwent radioactive
      ablation of the thyroid gland. The patient subsequently developed hypothyroidism
      and required a much higher dose of levothyroxine than his weight-based estimate
      of a full replacement dose to maintain euthyroidism. On 325 micog of daily
      levothyroxine the patient was clinically euthyroid and had a normal TSH although
      his levels of T3 and T4 were high. Work-up revealed a mutation in the thyroid
      hormone beta-receptor gene, consistent with diagnosis of RTH. CONCLUSIONS: RTH is
      often misdiagnosed as Graves' disease. However, these disorders can coexist, and
      the concurrent presence of both disorders in a patient can present diagnostic
      challenges. A previous report of a patient with Graves' disease associated with
      RTH was published before gene sequencing could be used to confirm diagnosis of
      RTH. We present a patient with Graves' disease and concurrent RTH that was
      confirmed by gene sequencing, showing a mutation in the thyroid hormone receptor
      beta gene.

PMID- 20151831
TI  - Lateral ectopic thyroid goiter with a normally located thyroid.
AB  - BACKGROUND: Midline ectopic thyroid tissue is a common pathological entity. In
      contrast, laterally located ectopic thyroid tissue with a normally located
      thyroid gland is a very rare condition in head and neck surgery. SUMMARY: We
      report the association of laterally located multinodular thyroid tissue and a
      normally located multinodular goiter. A woman was seen in the otolaryngology
      clinic with a right submandibular mass. Clinical examination and investigations
      confirmed the presence of a multinodular goiter in an ectopic thyroid gland.
      CONCLUSION: Laterally located ectopic thyroid tissue is a very rare condition.
      Ectopic thyroid tissues can undergo the same pathological changes as a normally
      located thyroid gland. Ectopic thyroid goiter together with a normally located
      multinodular goiter is a rare entity, and this is the first to be reported in
      North America.

PMID- 20151832
TI  - Reference values for thyroid function tests in pregnant women living in
      Catalonia, Spain.

PMID- 20151834
TI  - Clinical presentation of primary thyroid tuberculosis.

PMID- 20151833
TI  - Graves' disease and massive thymic hyperplasia.

PMID- 20151835
TI  - The clinical role of molecular imaging: positron emission tomography/computed
      tomography and (90)yttrium-DOTATOC in the management of medullary thyroid cancer.

PMID- 20151836
TI  - Superior vena cava syndrome and substernal goiter.

PMID- 20151837
TI  - The association between benign paroxysmal positional vertigo and autoimmune
      chronic thyroiditis is not related to thyroid status.

PMID- 20151839
TI  - Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for
      the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection.
AB  - BACKGROUND: The MERIT (Maraviroc versus Efavirenz in Treatment-Naive Patients)
      study compared maraviroc and efavirenz, both with zidovudine-lamivudine, in
      antiretroviral-naive patients with R5 human immunodeficiency virus type 1 (HIV-1)
      infection. METHODS: Patients screened for R5 HIV-1 were randomized to receive
      efavirenz (600 mg once daily) or maraviroc (300 mg once or twice daily) with
      zidovudine-lamivudine. Coprimary end points were proportions of patients with a
      viral load <400 and <50 copies/mL at week 48; the noninferiority of maraviroc was
      assessed. RESULTS: The once-daily maraviroc arm was discontinued for not meeting
      prespecified noninferiority criteria. In the primary 48-week analysis (n = 721),
      maraviroc was noninferior for <400 copies/mL (70.6% for maraviroc vs 73.1% for
      efavirenz) but not for <50 copies/mL (65.3% vs 69.3%) at a threshold of -10%.
      More maraviroc patients discontinued for lack of efficacy (11.9% vs 4.2%), but
      fewer discontinued for adverse events (4.2% vs 13.6%). In a post hoc reanalysis
      excluding 107 patients (15%) with non-R5 screening virus by the current, more
      sensitive tropism assay, the lower bound of the 1-sided 97.5% confidence interval
      for the difference between treatment groups was above -10% for each end point.
      CONCLUSIONS: Twice-daily maraviroc was not noninferior to efavirenz at <50
      copies/mL in the primary analysis. However, 15% of patients would have been
      ineligible for inclusion by a more sensitive screening assay. Their retrospective
      exclusion resulted in similar response rates in both arms Trial registration.
      ClinicalTrials.gov identifier: (NCT00098293) .

PMID- 20151840
TI  - Activation of CD8 T cells predicts progression of HIV infection in women
      coinfected with hepatitis C virus.
AB  - BACKGROUND: Because activation of T cells is associated with human
      immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in
      patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting
      reports regarding effects of HCV on HIV disease progression. METHODS: Kaplan
      Meier and multivariate Cox regression models were used to study the risk of
      incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with
      HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV
      positive viremic women with HIV coinfection (median follow-up time, 5.2 years).
      For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR
      (DR) and/or CD38 were evaluated. RESULTS: HCV-positive viremic women had a
      statistically significantly higher percentage of activated CD8 T cells (P < .001)
      and a statistically significantly higher incidence of AIDS compared with HCV
      negative women (P < .001 [log-rank test]). The AIDS risk was greater among HCV
      positive viremic women in the highest tertile compared with the lowest tertile
      (>43% vs <26%) of CD8(+)CD38(+)DR(+) T cells (hazard ratio, 2.94 [95% confidence
      interval, 1.50-5.77]; P = .001). This difference was not observed in the HCV
      negative women (hazard ratio, 1.87 [95% confidence interval, 0.80-4.35]; P =
      .16). In contrast, CD4 activation predicted AIDS in both groups similarly.
      Increased percentages of CD8(+)CD38(-)DR(+), CD4(+)CD38(-)DR(-), and CD8(+)CD38(
      )DR(-) T cells were associated with a >60% decreased risk of AIDS for HCV
      positive viremic women and HCV-negative women. CONCLUSION: HCV-positive viremic
      women with HIV coinfection who have high levels of T cell activation may have
      increased risk of AIDS. Earlier treatment of HIV and HCV infection may be
      beneficial.

PMID- 20151841
TI  - Enhanced indoleamine 2,3-dioxygenase activity in patients with severe sepsis and
      septic shock.
AB  - BACKGROUND: Severe sepsis results in a sustained deleterious immune
      dysregulation. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of
      tryptophan catabolism, plays a pivotal role in immune tolerance and is induced
      during various inflammatory conditions. METHODS: Plasma samples obtained from
      patients with septic shock (n = 38), severe sepsis (n = 35), or sepsis (n = 10)
      and from healthy donors (n = 26) were analyzed for IDO activity by high
      performance liquid chromatography. Lymphocyte, monocyte, and regulatory T cell
      counts as well as monocytic human leukocyte antigen DR (HLA-DR) expression were
      quantified by flow cytometry. Peripheral blood mononuclear cells and purified
      CD14(+) and CD14(-) fractions were assayed in vitro for spontaneous and inducible
      IDO expression and activity. RESULTS: IDO activity gradually increased according
      to sepsis severity, and septic patients who died had higher IDO activity on
      admission than did survivors (P = .013). Monocytes were a major source of active
      IDO in normal peripheral blood. The percentage and absolute number of circulating
      CD14(+) cells were increased in septic patients, and their monocytes remained
      fully able to produce functional IDO after NF-kappaB-independent interferon gamma
      stimulation but not through NF-kappaB-dependent Toll-like receptor engagement.
      CONCLUSIONS: IDO activity is increased during severe sepsis and septic shock and
      is associated with mortality. IDO production could be used to better characterize
      monocyte reprogramming in sepsis.

PMID- 20151842
TI  - Wiring the streptococcal network for alternative lifestyles.

PMID- 20151843
TI  - Maraviroc for treatment-naive patients with HIV-1 infection: is the glass half
      empty or half full?

PMID- 20151844
TI  - Dissection of the molecular basis for hypervirulence of an in vivo-selected
      phenotype of the widely disseminated M1T1 strain of group A Streptococcus
      bacteria.
AB  - Group A streptococci (GAS) may engage different sets of virulence strategies,
      depending on the site of infection and host context. We previously isolated 2
      phenotypic variants of a globally disseminated M1T1 GAS clone: a virulent wild
      type (WT) strain, characterized by a SpeB(+)/SpeA(-)/Sda1(low) phenotype, and a
      hypervirulent animal-passaged (AP) strain, better adapted to survive in vivo,
      with a SpeB(-)/SpeA(+)/Sda1(high) phenotype. This AP strain arises in vivo due to
      the selection of bacteria with mutations in covS, the sensor part of a key 2
      component regulatory system, CovR/S. To determine whether covS mutations explain
      the hypervirulence of the AP strain, we deleted covS from WT bacteria (DeltaCovS)
      and were able to simulate the hypervirulence and gene expression phenotype of
      naturally selected AP bacteria. Correction of the covS mutation in AP bacteria
      reverted them back to the WT phenotype. Our data confirm that covS plays a direct
      role in regulating GAS virulence.

PMID- 20151845
TI  - Emerging MEK inhibitors.
AB  - IMPORTANCE OF THE FIELD: The Ras/Raf/MEK/ERK pathway is often activated by
      genetic alterations in upstream signaling molecules. Integral components of this
      pathway such as Ras and B-Raf are also activated by mutation. The Ras/Raf/MEK/ERK
      pathway has profound effects on proliferative, apoptotic and differentiation
      pathways. This pathway can often be effectively silenced by MEK inhibitors. AREAS
      COVERED BY THIS REVIEW: This review will discuss targeting of MEK which could
      lead to novel methods to control abnormal proliferation which arises in cancer
      and other proliferative diseases. This review will cover the scientific
      literature from 1980 to present and is a follow on from a review which focused on
      Emerging Raf Inhibitors published in this same review series. WHAT THE READER
      WILL GAIN: By reading this review the reader will understand the important roles
      that genetics play in the response of patients to MEK inhibitors, the potential
      of combining MEK inhibitors with other types of therapy, the prevention of
      cellular aging and the development of cancer stem cells. TAKE HOME MESSAGE:
      Targeting MEK has been shown to be effective in suppressing many important
      pathways involved in cell growth and the prevention of apoptosis. MEK inhibitors
      have many potential therapeutic uses in the suppression of cancer, proliferative
      diseases and aging.

PMID- 20151846
TI  - Fulvestrant: a unique antiendocrine agent for estrogen-sensitive breast cancer.
AB  - IMPORTANCE OF THE FIELD: The role of estrogen deprivation for the treatment of
      breast cancer has been understood since the 1800s. Pharmacologic advances in the
      field in the past decades, including tamoxifen and the aromatase inhibitors, have
      contributed significantly to the reduced mortality of estrogen-sensitive breast
      cancer. However, this subtype of breast cancer still presents with relapses and,
      once metastatic, progression to hormone-refractory state and loss of disease
      control remain an expected disease course. Fulvestrant, a pure estrogen receptor
      downregulator, is a new addition to the antiestrogen therapeutic armamentarium
      since its FDA approval in 2002. Its unique mechanism of action offers potential
      advantages over other estrogen targeted therapies. AREAS COVERED IN THIS REVIEW:
      Published scientific literature, including presented abstracts, on fulvestrant
      from 1985 to the present were reviewed with selected publications included. WHAT
      THE READER WILL GAIN: This review addresses current issues and therapies for
      estrogen-sensitive breast cancer, highlights the role of fulvestrant in current
      treatment guidelines and outlines some of the ongoing investigations of this
      compound. TAKE HOME MESSAGE: Fulvestrant is an effective and well-tolerated drug
      for treatment of metastatic estrogen-sensitive breast cancer. Work is underway to
      enhance its clinical benefit to patients as a single agent and in combination
      with other therapies.

PMID- 20151848
TI  - Impaired trafficking and intracellular retention of mutant kidney anion exchanger
      1 proteins (G701D and A858D) associated with distal renal tubular acidosis.
AB  - Novel compound heterozygous mutations, G701D, a recessive mutation, and A858D, a
      mild dominant mutation, of human solute carrier family 4, anion exchanger, member
      1 (SLC4A1) were identified in two pediatric patients with distal renal tubular
      acidosis (dRTA). To examine the interaction, trafficking, and cellular
      localization of the wild-type and two mutant kidney AE1 (kAE1) proteins, we
      expressed the proteins alone or together in human embryonic kidney (HEK) 293T and
      Madin-Darby canine kidney (MDCK) epithelial cells. In individual expressions,
      wild-type kAE1 was localized at the cell surface of HEK 293T and the basolateral
      membrane of MDCK cells. In contrast, kAE1 G701D was mainly retained
      intracellularly, while kAE1 A858D was observed intracellularly and at the cell
      surface. In co-expression experiments, wild-type kAE1 formed heterodimers with
      kAE1 G701D and kAE1 A858D, and promoted the cell surface expression of the mutant
      proteins. The co-expressed kAE1 G701D and A858D could also form heterodimers but
      showed predominant intracellular retention in HEK 293T and MDCK cells. Thus
      impaired trafficking of the kAE1 G701D and A858D mutants would lead to a profound
      decrease in functional kAE1 at the basolateral membrane of alpha-intercalated
      cells in the distal nephron of the patients with dRTA.

PMID- 20151849
TI  - Advances with the use of bio-inspired vectors towards creation of artificial
      viruses.
AB  - IMPORTANCE OF THE FIELD: In recent years, there has been a great deal of interest
      in the development of recombinant vectors based on biological motifs with
      potential applications in gene therapy. Several such vectors have been
      genetically engineered, resulting in biomacromolecules with new properties that
      are not present in nature. AREAS COVERED IN THIS REVIEW: This review briefly
      discusses the advantages and disadvantages of the current state-of-the-art gene
      delivery systems (viral and non-viral) and then provides an overview on the
      application of various biological motifs in vector development for gene delivery.
      Finally, it highlights some of the most advanced bio-inspired vectors that are
      designed to perform several self-guided functions. WHAT THE READER WILL GAIN:
      This review helps the readers get a better understanding about the history and
      evolution of bio-inspired fusion vectors with the potential to merge the
      strengths of both viral and non-viral vectors in order to create efficient, safe
      and cost-effective gene delivery systems. TAKE HOME MESSAGE: With the emergence
      of new technologies such as recombinant bio-inspired vectors, it may not take
      long before non-viral vectors are observed that are not just safe and tissue
      specific, but even more efficient than viral vectors.

PMID- 20151847
TI  - Pharmacologic approaches to treatment resistant depression: a re-examination for
      the modern era.
AB  - IMPORTANCE OF THE FIELD: Treatment-resistant depression (TRD) is common and
      debilitating. Initial treatment is often insufficient to achieve full remission
      in a given depressive episode, resulting in more frequent episodes, worsened
      severity, and major disability. AREAS COVERED IN THIS REVIEW: This review surveys
      literature on the diagnosis and pharmacological management of TRD in light of
      recent developments. Evidence regarding commonly used treatment options is
      critically examined and key recommendations are offered. The review ends by
      considering drugs acting on the melatonin, acetylcholine, and glutamate systems
      that hold promise as future options for TRD. WHAT THE READER WILL GAIN: Recent
      trends and research findings have impacted how the evidence supporting different
      approaches to TRD should be evaluated. For example, many earlier TRD studies
      employed tricyclics as the primary antidepressant, but tricyclics have now been
      superseded by selective serotonin reuptake inhibitors (SSRIs) in routine clinical
      practice. This deficiency has been addressed by the Sequenced Treatment
      Alternatives to Relieve Depression (STAR*D) study, the largest effectiveness
      study of TRD ever conducted. However, design characteristics of the STAR*D study
      preclude simple comparisons with earlier studies. TAKE HOME MESSAGE: A
      shortcoming of most treatment recommendations for TRD is their reliance on older
      studies that do not reflect the current preeminence of SSRIs in clinical
      practice. This has distorted the prioritization of pharmacological strategies for
      TRD. Efforts to correct this distortion with effectiveness research, designed to
      better reflect current practice trends, require critical consideration of the
      strengths and limitations of this approach.

PMID- 20151850
TI  - Effect of polyoxyethylene sorbitan esters and sodium caseinate on physicochemical
      properties of palm-based functional lipid nanodispersions.
AB  - The main objective of the present study was to investigate the effect of
      polyoxyethylene sorbitan esters and sodium caseinate on physicochemical
      properties of palm-based functional lipid nanodispersions prepared by the
      emulsification-evaporation technique. The results indicated that the average
      droplet size increased significantly (P < 0.05) by increasing the chain length of
      fatty acids and also by increasing the hydrophile-lipophile balance value. Among
      the prepared nanodispersions, the nanoemulsion containing Polysorbate 20 showed
      the smallest average droplet size (202 nm) and narrowest size distribution for
      tocopherol-tocotrienol nanodispersions, while sodium caseinate-stabilized
      nanodispersions containing carotenoids had the largest average droplet size (386
      nm), thus indicating a greater emulsifying role for Polysorbate 20 compared with
      sodium caseinate.

PMID- 20151851
TI  - Neuropsychiatric evaluation of patients with brucellosis.
AB  - Brucellosis is a multisystem disease that may present with a broad spectrum of
      clinical manifestations. Neurobrucellosis is one of the complications. The
      objective of this study was to determine neuropsychiatric manifestations among
      patients with brucellosis. Twenty-seven consecutive patients with brucellosis (14
      patients with manifest neurological manifestation and 13 patients without
      apparent neurological manifestation) were recruited from Assiut University
      hospital and compared with 50 healthy controls matched with respect to age, sex,
      and social economic and educational levels. They were subjected to systemic,
      meticulous neuropsychiatric evaluations, laboratory, radiological,
      neurophysiology, and psychometric assessment with Mini-Mental State Examination,
      Wechsler Memory Scale-Revised. and Hamilton Depression Rating. Overt or apparent
      neurological manifestation was recorded in 14 patients (51.85%) and 13 patients
      (48.15%) with brucellosis without apparent neuropsychiatric involvement. Central
      nervous system (CNS) involvement (vascular stroke, meningeoencephalitis, and
      dementia) was recorded in 9 patients (33.3%) and 6 patients (22.2%) had
      peripheral nervous sytem (PNS) involvement (polyneuropathy, radiculoapathy, and
      polyradiculoneuropathy). Depression was recorded in 7 (29.2%) patients; 3
      patients (21.4%) of the neurobrucellosis group and 4 patients (30.8%) with
      brucellosis without neurological manifestations. Patients with brucellosis
      (neurobrucellosis and patients without neurological manifestations) reported
      highly significant impairment in some cognitive function measures (mental
      control, logical memory, visual reproduction) and higher scores on depressive
      symptoms compared with controls. Patients with a Brucella infection usually
      manifest central nervous system involvement. Clinicians, especially serving in
      endemic areas or serving patients coming from endemic areas, should consider the
      likelihood of neurobrucellosis in patients with unexplained neurological and
      psychiatric symptoms, and should perform the necessary tests, including cognitive
      function and depression tests.

PMID- 20151852
TI  - Non-protected carotid artery stent without angioplasty in high-risk patients with
      carotid and coronary artery disease undergoing cardiac surgery.
AB  - Hemodynamic depression (HD) is a frequent complication related to carotid
      endartherectomy or carotid artery stenting (CAS), often not well tolerated in
      patients with coronary artery disease. The purpose of this study is to assess
      whether CAS without angioplasty is beneficial in patients with severe carotid
      artery disease before coronary revascularization surgery (CABG) regarding the
      occurrence of HD. Between October 2002 and August 2006, 39 CAS were performed in
      35 patients before cardiac surgery. Outcome measures, including periprocedural
      and 30-day post stenting and cardiac surgery complications, were assessed. Twenty
      seven patients underwent CABG and eight combined CABG and valve replacement.
      During or immediately after CAS there was no episode of bradycardia or
      hypotension necessitating medical treatment. In the period between CAS-CABG,
      there was no case of HD. We also found no myocardial infarction. There were five
      neurological complications, two of them in the period between CAS-CABG (one
      transitory ischemic attack (TIA) and one minor stroke) and three after CABG (one
      TIA and two strokes). Three of them were discharged symptom-free. CAS without
      angioplasty can be a safe alternative to treat patients with coexistence of
      carotid and cardiac disease, since does not produce hemodynamic depression,
      therefore diminishing the cardiac complications.

PMID- 20151853
TI  - Independent testing of the Fisher & Paykel Healthcare MR860 Laparoscopic
      Humidification System.
AB  - In laparoscopic surgery CO2 is commonly insufflated at room temperature, with a
      relative humidity approaching 0%. There has been an increase in utilization of
      devices to warm and humidify the insufflated gas to avoid potential detrimental
      effects caused by desiccation. Available data on the performance of these devices
      are limited. We aimed to conduct independent testing of the Fisher & Paykel MR860
      Laparoscopic Humidification System at variable flow rates. A 2.5l insulated
      chamber was constructed and a digital thermo-hygrometer placed inside it. The
      humidifier water vessel was weighed and exactly 30.0g of water poured in. 50.0L
      of CO2 was insufflated into the chamber via the humidifier at 2.0L/min, 4.0l/min,
      6.0l/min, 8.0l/min, and 10l/min using a laparoscopic insufflator. Measurements of
      temperature and humidity in the chamber were taken at 30 second intervals. After
      50.0l of gas was insufflated the water left in the humidifier was weighed, and
      this was used to calculate the mean absolute humidity of the insufflated gas by
      the gravimetric method. At every flow rate, > 98.0% relative humidity was
      achieved in the chamber after less than 30 seconds of insufflation. Using the
      gravimetric estimate, the humidifier was able to saturate 50.0l of CO2 to close
      to saturation humidity at every flow rate tested. The Fisher & Paykel MR860
      Laparoscopic Humidification System effectively humidifies insufflated CO2 at a
      range of flow rates commonly used in the surgical setting.

PMID- 20151854
TI  - Endoscopic palliation of malignant obstructive jaundice in extremely elderly
      patients: plastic stent is enough.
AB  - Although the price of biliary metal stents is manyfold higher when compared to
      plastic stents, the lower frequency of recurrent obstructions makes metal stents
      superior to plastic stents for endoscopic palliation of malignant biliary
      stricture in most patients. Is this the case in extremely elderly patients as
      well? A retrospective data review comprising prospective data collection and
      double-entry bookkeeping of therapeutic endoscopic retrograde
      cholangiopancreatographies (ERCP) with biliary strictures referring to malignancy
      in 14 patients aged 90 years or older at our institution in 1997-2007. Plastic
      stents were successfully inserted in 11 out of 14 patients, yielding a technical
      success rate of 79 %. In the remaining three patients, high biliary obstruction
      was relieved percutaneously in two cases while the general condition of one
      patient was so poor that terminal care decision was made in that case. There was
      no recurrent biliary obstruction in any of the patients with plastic stents prior
      to death which occurred after a mean of 2.8 months, giving a clinical success
      rate of 100 %. To be concluded, in extremely elderly patients with malignant
      obstructive jaundice, palliation with plastic stent is effective enough.

PMID- 20151855
TI  - The somatostatin receptor subtype 5 in neuroendocrine tumours.
AB  - IMPORTANCE OF THE FIELD: In recent years, scientific work has been intensified to
      unravel new (patho-) physiological insights, particularly regarding the
      functional role of somatostatin (SRIF) receptor subtype 5 (sst) and the
      development of novel sst(5)-targeted SRIF analogues, in order to broaden medical
      therapeutic opportunities in patients suffering from neuroendocrine diseases.
      AREAS COVERED IN THIS REVIEW: The scope of this review is primarily focused upon
      recent insights in sst(5)-receptor physiology, novel sst(5)-targeted treatment
      options predominantly directed towards pituitary adenomas, and
      gastroenteropancreatic neuroendocrine tumours. WHAT THE READER WILL GAIN: An
      understanding of the potential that novel sst(5)-targeted SRIF analogues might
      have in the medical treatment of Cushing's disease and acromegaly, as
      demonstrated by translational research, based on pathophysiological data combined
      with results from clinical trials. TAKE HOME MESSAGE: The role of targeting
      sst(5) in gastroenteropancreatic neuroendocrine tumours remains to be
      established. The sst(5) subtype might function as sst(2) modulator in terms of
      receptor internalization and desensitization, and seems less important compared
      with sst(2)-preferring SRIF analogues in the regulation of human insulin
      secretion by the pancreas. Finally, absence of sst(5) in corticotroph adenomas
      could be related to tumour aggressiveness in Cushing's disease.

PMID- 20151856
TI  - Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?
AB  - IMPORTANCE OF THE FIELD: The macrolides are a class of antibiotics widely
      prescribed in infectious disease. More recently, there has been considerable
      interest in potential indications for these agents, in addition to their simple
      antibacterial indications, in a number of lung pathophysiologies. AREAS COVERED
      IN THIS REVIEW: Demonstrated clinical efficacy of macrolides in diseases such as
      diffuse panbronchiolitis was difficult to ascribe to a direct antimicrobial
      action. More recently, positive experiences in dealing with post-transplant
      bronchiolitis obliterans syndrome suggests that other chronic lung diseases may
      benefit from macrolide therapy. This is important, as the treatment options for
      such diseases are often very limited. In this review, potential antibiotic and
      non-antibiotic beneficial actions of macrolide therapy are discussed and
      conclusions drawn from a limited but growing literature. WHAT THE READER WILL
      GAIN: The reader will gain an overview of lung diseases that may benefit from
      macrolides, and a consideration of the possible mechanisms underlying such
      benefit. TAKE HOME MESSAGE: The key message from our review is that this class of
      agents may prove to be a useful therapeutic option for a range of respiratory
      diseases, but that further trials and mechanistic studies are required to clarify
      their role.

PMID- 20151859
TI  - Practicing veterinary medicine in a recession.

PMID- 20151860
TI  - What is your diagnosis? Portocaval shunt.

PMID- 20151861
TI  - Diagnostic imaging in veterinary dental practice. Periapical lesions associated
      with the left maxillary molar teeth and associated cellulitis.

PMID- 20151862
TI  - Pathology in practice. Granulomatous pneumonia, prostatitis and uveitis with
      intralesional yeasts consistent with Blastomyces.

PMID- 20151863
TI  - What is the evidence? Therapeutic foods for cats with chronic kidney disease.

PMID- 20151864
TI  - Distribution of actively employed US veterinarians by state and gender, 2003
      2008.

PMID- 20151865
TI  - Association between naturally occurring chronic kidney disease and feline
      immunodeficiency virus infection status in cats.
AB  - OBJECTIVE: To investigate the association between naturally occurring chronic
      kidney disease (CKD) and FIV infection status in cats in Australia. DESIGN: Case
      control study. ANIMALS: 73 cats with CKD and 69 cats without historical,
      physical, or clinicopathologic evidence of CKD. PROCEDURES: Cats were tested for
      serum antibodies against FIV glycoprotein 40 (gp40) by use of an immunomigration
      assay. Information regarding age, breed (purebred or domestic), and sex was
      obtained from medical records. Analysis was performed on data from cats
      stratified into 2 age categories (< 11 years old and >or= 11 years old).
      Univariable and then multivariable analyses were performed to investigate the
      relationship between CKD and the study variable (FIV infection), the latter
      analysis accounting for breed (purebred or domestic), sex, and veterinary
      hospital of origin. RESULTS: Results of multivariable analysis revealed that
      younger cats with CKD (< 11 years old) were significantly more likely to have
      positive test results for serum antibodies against FIV gp40 than were cats
      without CKD. No significant associations were found between CKD and FIV
      infection, breed, sex, or hospital of origin among older (>or= 11 years old) cats
      in the multivariable analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Among cats <
      11 years of age, those with CKD were significantly more likely to have positive
      test results for serum antibodies against FIV gp40 than were cats without CKD. It
      cannot be definitively established from results of this study whether infection
      with FIV preceded the development of CKD, and the role, if any, of FIV in the
      establishment or progression of CKD remains to be determined.

PMID- 20151866
TI  - Ambulatory electrocardiographic evaluation of clinically normal adult Boxers.
AB  - OBJECTIVE: To determine the prevalence of ventricular arrhythmias in clinically
      normal adult Boxers. DESIGN: Prospective cross-sectional study. ANIMALS: 301
      Boxers (181 females and 120 males) > 1 year old with echocardiographically normal
      systolic function and no history of syncope or congestive heart failure.
      PROCEDURES: Physical examination, which included echocardiography, was performed
      on all dogs. A 24-hour ambulatory ECG was performed on each dog, and results were
      evaluated to assess ventricular arrhythmias. Statistical evaluation was performed
      to determine correlations between the total number of ventricular premature
      complexes (VPCs)/24 h, grade of ventricular arrhythmia, and age of the dogs.
      RESULTS: Age of dogs ranged from 1 to 16 years (median, 4 years). Number of
      VPCs/24 h in each dog ranged from 0 to 62,622 (median, 6 VPCs/24 h). Grade of
      arrhythmias ranged from 0 to 3 (median, 1). Age was correlated significantly with
      number of VPCs/24 h (r = 0.43) and with grade of arrhythmia (r = 0.37). Number of
      VPCs/24 h was significantly correlated with grade of arrhythmia (r = 0.82).
      CONCLUSIONS AND CLINICAL RELEVANCE: Clinically normal adult Boxers generally had
      < 91 VPCs/24 h and an arrhythmia grade < 2. Boxers with > 91 VPCs/24 h were
      uncommon and may have represented dogs with arrhythmogenic right ventricular
      cardiomyopathy or other disease processes that could have resulted in the
      development of ventricular arrhythmias.

PMID- 20151868
TI  - Open heart closure of an atrial septal defect by use of an atrial septal occluder
      in a dog.
AB  - CASE DESCRIPTION: A 3-year-old sexually intact male Standard Poodle was admitted
      to the veterinary teaching hospital for transcatheter closure of a large atrial
      septal defect (ASD). CLINICAL FINDINGS: The dog had exercise intolerance and was
      thin. Findings on physical examination were within normal limits with the
      exception of a left base systolic heart murmur (grade 5/6). The dog was not
      receiving any medications. Echocardiography and thoracic radiography confirmed
      the diagnosis of ASD and revealed compensatory changes consistent with a large
      left to right shunting ASD. Results of serum biochemical analysis and CBC were
      within reference range limits. TREATMENT AND OUTCOME: Transcatheter ASD closure
      with an atrial septal occluder (ASO) was performed and failed. An open heart
      surgical approach under cardiopulmonary bypass was declined by the dog's owners.
      The dog underwent a novel hybrid approach involving active device fixation under
      temporary inflow occlusion after transatrial device deployment. The dog recovered
      with some manageable postoperative complications. As of the last follow-up
      examination, the dog had 10 months of event-free survival. CLINICAL RELEVANCE:
      Transcatheter closure by use of an ASO and open heart patch repair with
      cardiopulmonary bypass to surgically treat dogs with ASD has been reported.
      Transcatheter closure is not possible in dogs with large ASD. The novel hybrid
      procedure reported herein represented a viable alternative to euthanasia.

PMID- 20151870
TI  - Prevalence of various presale radiographic findings and association of findings
      with sales price in Thoroughbred yearlings sold in Kentucky.
AB  - OBJECTIVE: To estimate prevalences of various presale radiographic findings and
      of presale arthroscopy in horses offered for sale at the 2006 Keeneland September
      yearling sale and to compare sales prices between yearlings with and without
      various presale radiographic findings or a history of arthroscopy. ANIMALS: 397
      Thoroughbred yearlings. DESIGN: Cross-sectional study. PROCEDURES: Presale
      radiographs and health records were examined to estimate prevalences of various
      radiographic findings and presale arthroscopy. Sales price records were used to
      compare sales prices between yearlings with and without various presale
      radiographic findings or a history of arthroscopy. RESULTS: In the forelimbs, the
      most common radiographic findings were vascular channels in the proximal sesamoid
      bones (23%), enthesophytes or osteophytes in the radiocarpal joint (22%), and
      osteochondritis lesions involving the sagittal ridge of the third metacarpal bone
      (20%). In the hind limbs, the most common radiographic findings were
      enthesophytes or osteophytes involving the proximal sesamoid bones (39%),
      abnormalities of the distodorsal aspect of the third metatarsal bone (36%),
      enthesophytes or osteophytes involving the distal intertarsal joint (27%), and
      osteochondritis lesions involving the stifle joint (8%). Thirteen percent of
      horses had a history of presale arthroscopy. Median sales price was significantly
      lower in horses with fragments of the proximal phalanx than in horses without.
      Median sales price was significantly higher in horses with a history of presale
      arthroscopy than in horses without. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      revealed significant associations between a diagnosis of fragments of the
      proximal phalanx, presale arthroscopy, and sales price in Thoroughbred yearlings.

PMID- 20151871
TI  - Phosphine intoxication following oral exposure of horses to aluminum phosphide
      treated feed.
AB  - CASE DESCRIPTION: 66 horses were potentially exposed to phosphine (a gas) 14
      hours after being fed a pelleted ration treated with aluminum phosphide. CLINICAL
      FINDINGS: 28 horses had clinical signs of profuse sweating, tachycardia,
      tachypnea, pyrexia, ataxia, seizures, and widespread muscle tremors. Clinically
      relevant laboratory findings included hypoglycemia and high plasma concentrations
      of lactate and ammonia and activities of gamma-glutamyl transpeptidase, aspartate
      aminotransferase, and alkaline phosphatase. At least 4 horses had signs
      consistent with hepatic encephalopathy. Necropsy findings included petechial and
      ecchymotic hemorrhages in multiple organs, widespread vascular congestion,
      hepatic lipidosis, and neuronal necrosis in the brain. Phosphine was detected in
      the stomachs of the 3 horses tested. TREATMENT AND OUTCOME: On the farm, horses
      were treated with gastric lavage followed by administration of di-tri-octahedral
      smectite, atropine, fluids, and sedatives. Six horses were hospitalized, and
      lactated Ringer's solution and flunixin meglumine were administered IV.
      Additionally, 10% dextrose, corn syrup, and di-tri-octahedral smectite were
      administered PO. Twenty-seven horses died within 2 days after exposure. Two
      survivors (1 without clinical signs of toxicosis) made a complete recovery.
      CLINICAL RELEVANCE: Progression of clinical signs in affected horses in this
      report was rapid, with few treatment options available, leading to a high case
      fatality rate. Fumigation with aluminum phosphide is commonly performed to
      eliminate weevils and other insects from stored grains. When appropriate
      precautions are used during fumigation, risk to livestock is typically minimal.

PMID- 20151873
TI  - An autoradiographic study of cochlea and organs of guinea pigs after
      intraperitoneal injection of 125I-labelled bFGF.
AB  - CONCLUSION: The results of our research indicate that 125I-labelled basic
      fibroblast growth factor (125I-bFGF) has some difficulty in getting across the
      blood-labyrinth barrier (BLB). Therefore, it is necessary to carry out further
      study on the route of bFGF administration. OBJECTIVE: To observe whether bFGF
      could pass through the BLB after intraperitoneal injection and to establish an
      experimental basis for its clinical applications. METHODS: Thirty guinea pigs
      were divided into three equal groups. Animals in group 1 were administered 125I
      bFGF, while animals in groups 2 and 3 were given 125I or saline solution,
      respectively, via intraperitoneal injection. The animals were sacrificed 2 h
      later and samples of blood, brain, cochlea, thyroid gland, heart, liver, and
      kidney were collected and weighed. A radioimmunoassay analyzer was employed to
      count the CPM values of each sample, and autoradiography was performed on section
      samples of both cochleae. RESULTS: The CPM value of organ samples in the 125I
      group was higher than that in other groups, and radioactive grain was observed in
      cochlear samples of this group. In the 125I-bFGF group, blood demonstrated the
      highest CPM value, while cochlea and brain demonstrated the lowest CPM value,
      with no radioactive grain observed in cochlear samples.

PMID- 20151874
TI  - Cartilage reinforcement tympanoplasty: otological and audiological results.
AB  - CONCLUSION: High risk perforations including total, subtotal, atelectatic
      perforations, those with cholesteatoma and revision cases can be treated
      efficiently with cartilage reinforcement tympanoplasty. OBJECTIVE: The purpose of
      this study was to describe the perforation closure rates and hearing results of
      cartilage reinforcement tympanoplasty. METHODS: This was a retrospective chart
      review and included 60 patients who underwent surgery with the cartilage
      reinforcement technique between November 2006 and October 2008 at the Department
      of Otorhinolaryngology of Haydarpasa Numune Research and Training Hospital,
      Istanbul, Turkey. The male to female ratio was 28 (46.7%)/32 (53.3%). The mean
      age of the patients was 30.10 +/- 11.50 years (range 13-55). RESULTS:
      Preoperatively, only one patient had a retraction pocket but not a perforation,
      12 (20%) patients had perforation of < 25% of the total tympanic membrane
      diameter, 12 patients had perforation between 25% and 50% of the total membrane
      diameter, 18 patients had a perforation between 50% and 75% of total membrane
      diameter and 17 patients had a perforation of > 75% of the total membrane
      diameter. Postoperatively we achieved total closure of tympanic membrane
      perforations for 47 patients but the perforations of 13 patients remained in
      various sizes (7 patients had tympanic membrane perforation < 25% of the total
      membrane diameter, 3 between 25% and 50%, 2 between 50% and 75% and 1 patient had
      a perforation > 75% of the total membrane diameter). There was a statistically
      significant difference between percentages of preoperative perforation and
      postoperative perforations (p = 0.001). Only 1.7% of patients had no perforation
      preoperatively and this ratio increased to 78.3% postoperatively. Also, 30% of
      patients had a perforation between 50% and 75% of the total membrane diameter,
      28.3% of the patients had a perforation > 75% of the total membrane diameter
      preoperatively and this ratio decreased to 3.3% and 1.7%, respectively.
      Concerning the audiological parameters, the difference between preoperative and
      postoperative hearing levels was statistically significant (p = 0.001).

PMID- 20151875
TI  - Laser photocoagulation versus combined laser photocoagulation and posterior sub
      Tenon's triamcinolone injection for the primary treatment of diffuse diabetic
      macular edema.
AB  - PURPOSE: To evaluate the effectiveness of combined treatment with posterior sub
      Tenon's triamcinolone injection and focal laser photocoagulation, compared with
      laser treatment alone, in diffuse diabetic macular edema. METHODS: This was a
      nonrandomized, prospective, controlled study that involved 20 eyes with diffuse
      diabetic macular edema. The patients were divided into 2 groups: group I (10
      eyes) received focal laser photocoagulation alone; and group II (10 eyes)
      received combined focal laser photocoagulation and posterior sub-Tenon's
      triamcinolone injection. All patients were followed for 6 months. Main outcome
      measures were final visual outcome and fluorescein leakage and retreatment rates
      at the end of the follow-up period. RESULTS: Combined therapy showed better
      visual and angiographic outcome at 6 months. The retreatment rate was
      significantly lower in the combined-therapy group compared with the laser-therapy
      alone group, with more stable visual acuity. CONCLUSION: Improvement of visual
      acuity and decreased fluorescein leakage suggest that combination therapy with
      posterior sub-Tenon's triamcinolone injection and focal laser photocoagulation,
      particularly when used as a first-line therapy, is advantageous and merits
      further investigation.

PMID- 20151876
TI  - Non-invasive diagnosis of liver diseases by breath analysis using an optimized
      ion-molecule reaction-mass spectrometry approach: a pilot study.
AB  - Breath composition is altered in liver diseases. We tested if ion-molecule
      reaction mass spectrometry (IMR-MS) combined with a new statistical modality
      improves the diagnostic accuracy of breath analysis in liver diseases. We
      analysed 114 molecules in the breath of 126 individuals (healthy controls, and
      patients with non-alcoholic and alcoholic fatty liver disease and liver
      cirrhosis) by IMR-MS. Characteristic exhalation patterns were identified for each
      group. Combining two to seven molecules in the new stacked feature ranking model
      reached a diagnostic accuracy (area under the curve) for individual liver
      diseases between 0.88 and 0.97. IMR-MS followed by sophisticated statistical
      analysis is a promising tool for liver diagnostics by breath analysis.

PMID- 20151877
TI  - Masking effects of speech and music: does the masker's hierarchical structure
      matter?
AB  - Speech and music are time-varying signals organized by parallel hierarchical
      rules. Through a series of four experiments, this study compared the masking
      effects of single-talker speech and instrumental music on speech perception while
      manipulating the complexity of hierarchical and temporal structures of the
      maskers. Listeners' word recognition was found to be similar between
      hierarchically intact and disrupted speech or classical music maskers (Experiment
      1). When sentences served as the signal, significantly greater masking effects
      were observed with disrupted than intact speech or classical music maskers
      (Experiment 2), although not with jazz or serial music maskers, which differed
      from the classical music masker in their hierarchical structures (Experiment 3).
      Removing the classical music masker's temporal dynamics or partially restoring it
      affected listeners' sentence recognition; yet, differences in performance between
      intact and disrupted maskers remained robust (Experiment 4). Hence, the effect of
      structural expectancy was largely present across maskers when comparing them
      before and after their hierarchical structure was purposefully disrupted. This
      effect seemed to lend support to the auditory stream segregation theory.

PMID- 20151878
TI  - The adaptive pattern of the late auditory evoked potential elicited by repeated
      stimuli in cochlear implant users.
AB  - To describe the adaptive pattern of cortically generated auditory evoked
      potentials elicited by repeated stimuli via cochlear implants (CIs), the late
      auditory evoked potential (LAEP) was collected from nine postlingually deafened
      adult CI users. Tone bursts were presented in 30 trains consisting of 10 tone
      bursts each, with inter-stimulus intervals (ISIs) of 0.7 ms and inter-train
      intervals (ITIs) of 15s. The response to the first stimulus and the response to
      later tone bursts in the train were compared. Results showed that the LAEP for
      the first tone burst was larger than that for later tone bursts, displaying an
      adaptive pattern. This pattern appeared to be more prominent in CI users with
      good speech perception performance than in those with poorer performance. This
      finding is meaningful in the context of our future research to restore normal
      adaptation in CI users to improve their speech perception performance.

PMID- 20151879
TI  - The impact of health literacy on patient understanding of counseling and
      education materials.
AB  - Low health literacy is reported to have negative consequences on patient
      understanding of health-related information; however, there is a dearth of
      research regarding health literacy in an audiology-specific context. This study
      examines the grade level of language used in verbal and written communication
      samples during routine hearing aid orientation appointments. Patient counseling
      sessions were videotaped and transcribed; hearing aid instruction guides used
      during counseling sessions were also transcribed. The Flesch-Kincaid grade level
      formula was used to determine the approximate United States grade level
      equivalent of the counseling sessions, hearing aid instruction guides, and to
      predict patient health literacy. The results indicate that patient predicted
      health literacy likely impacts understanding of both one-on-one counseling and
      hearing aid instruction guides.

PMID- 20151881
TI  - Childhood auditory processing disorder as a developmental disorder: the case for
      a multi-professional approach to diagnosis and management.
AB  - Auditory processing disorder (APD) is diagnosed when a patient presents with
      listening difficulties which can not be explained by a peripheral hearing
      impairment or higher-order cognitive or language problems. This review explores
      the association between auditory processing disorder (APD) and other specific
      developmental disorders such as dyslexia and attention-deficit hyperactivity
      disorder. The diagnosis and aetiology of APD are similar to those of other
      developmental disorders and it is well established that APD often co-occurs with
      impairments of language, literacy, and attention. The genetic and neurological
      causes of APD are poorly understood, but developmental and behavioural genetic
      research with other disorders suggests that clinicians should expect APD to co
      occur with other symptoms frequently. The clinical implications of co-occurring
      symptoms of other developmental disorders are considered and the review concludes
      that a multi-professional approach to the diagnosis and management of APD,
      involving speech and language therapy and psychology as well as audiology, is
      essential to ensure that children have access to the most appropriate range of
      support and interventions.

PMID- 20151880
TI  - Prevalence and aetiology of congenitally deafblind people in Denmark.
AB  - A study of prevalence and aetiology was performed on 63 children and 127 adults
      in Denmark with congenital deafblindness. Using a Scandinavian definition of
      deafblindness, the prevalence of congenital deafblindness was found to be 1:29
      000. Thirty-five different aetiological causes of deafblindness were found.
      Causes of congenital deafblindness were different among adults compared to causes
      among children. Rubella syndrome (28%, n = 36) and Down syndrome (8%. n = 10)
      were the largest groups among people above 18 years of age. Among children CHARGE
      syndrome (16%, n = 13) was the largest group. Ethnicity was also evaluated. Among
      children 72% were Danish, but among the adults 98% were Danish. Implications of
      difference in aetiology and ethnicity are discussed in relation to the
      Scandinavian traditions of clinical practice and identification of congenital
      deafblindness.

PMID- 20151882
TI  - Effect of dichotic listening on self-reported state anxiety.
AB  - The present study examined the relationship between dichotic speech recognition
      and state anxiety. State anxiety, as determined by the State-Trait anxiety
      inventory (STAI), was measured pre- and post-dichotic testing in a group of young
      adults with normal hearing. Dichotic speech recognition was measured for three
      types of speech stimuli: 3-pair digits, monosyllabic words, and consonant-vowels.
      Results revealed significant increases in state anxiety as a function of dichotic
      testing for all stimulus types. There was not a significant difference, however,
      in state anxiety between the stimulus types. A subset of subjects (n=44) repeated
      the experiment a second time. There were no significant differences in state
      anxiety experienced due to dichotic listening between the two sessions. Results
      from the present study confirm that dichotic listening induces significant
      increases in state anxiety in a group of young adults with normal hearing.
      Although statistically significant, the mean increase in state anxiety does not
      exceed normative levels for college students. Further, the effect of anxiety on
      dichotic speech recognition performance appears minimal in this population.

PMID- 20151883
TI  - High frequency audiometric notch: an outpatient clinic survey.
AB  - It is a common misconception that high frequency audiometric notches are
      diagnostic of noise induced hearing loss. The aim of this study was to identify
      the prevalence of high frequency notch (HFN) in an audiovestibular medicine
      outpatient clinic population at a district general hospital. One hundred and
      forty nine consecutive adult patients were assessed. According to standard
      practice at the audiovestibular clinic, a full clinical history with particular
      emphasis on neuro-otological symptoms, noise exposure, and medical risk factors
      for sensorineural hearing loss was taken. After standard 8-frequency pure tone
      audiometry, subjects were divided into those with HFN and those without. There
      were 84 (56%) females and 65 (44%) males with a mean age of 45 years (range: 19
      to 91 years). A total of 39.6% had notches not attributable to noise
      (occupational or recreational) or any other known risk factor. In 29 (49.2%) and
      15 (25.4%) the HFN was present in the left and right ear respectively whereas 15
      (25.4%) were bilateral. The frequency least affected was 3 kHz while 4 kHz and 6
      kHz were affected in almost equal proportions. In 53 ears (71.6%), the notch
      depth was less than 20 dBHL (10-19 dB) compared to 21 ears (28.4%) with a depth
      of 20 dBHL or more. This study concludes that high frequency notch without
      excessive noise exposure or any other known factor is common. It is neither
      diagnostic of, nor invariable with NIHL unless a convincing history of hazardous
      noise exposure is elicited from the history.

PMID- 20151884
TI  - Transient-evoked and distortion product otoacoustic emissions: A short-term test
      retest reliability study.
AB  - Knowledge regarding the variability of transient-evoked otoacoustic emissions
      (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) is essential in
      clinical settings and improves their utility in monitoring hearing status over
      time. In the current study, TEOAEs and DPOAEs were measured with commercially
      available OAE-equipment in 56 normally-hearing ears during three sessions.
      Reliability was analysed for the retest measurement without probe-refitting, the
      immediate retest measurement with probe-refitting, and retest measurements after
      one hour and one week. The highest reliability was obtained in the retest
      measurement without probe-refitting, and decreased with increasing time-interval
      between measurements. For TEOAEs, the lowest reliability was seen at half-octave
      frequency bands 1.0 and 1.4 kHz; whereas for DPOAEs half-octave frequency band
      8.0 kHz had also poor reliability. Higher primary tone level combination for
      DPOAEs yielded to a better reliability of DPOAE amplitudes. External
      environmental noise seemed to be the dominating noise source in normal-hearing
      subjects, decreasing the reliability of emission amplitudes especially in the low
      frequency region.

PMID- 20151885
TI  - Analysis of auditory function using brainstem auditory evoked potentials and
      auditory steady state responses in infants with perinatal brain injury.
AB  - Approximately 2-4 % of newborns with perinatal risk factors present hearing loss.
      The aim of this study was to analyse the auditory function in infants with
      perinatal brain injury (PBI). Brainstem auditory evoked potentials (BAEPs),
      auditory steady state responses (ASSRs), and tympanometry studies were carried
      out in 294 infants with PBI (586 ears, two infants had unilateral microtia
      atresia). BAEPs were abnormal in 158 (27%) ears, ASSRs in 227 (39%), and
      tympanometry anomalies were present in 131 (22%) ears. When ASSR thresholds were
      compared with BAEPs, the assessment yielded 92% sensitivity and 68% specificity.
      When ASSR thresholds were compared with tympanometry results as an indicator of
      middle-ear pathology, the assessment gave 96% sensitivity and 77% specificity.
      When BAEP thresholds were compared with tympanometry results, sensitivity was 35%
      and specificity 95%. In conclusion, BAEPs are useful test for neonatal auditory
      screening; they identify with more accuracy sensorineural hearing losses. ASSRs
      are more pertinent for identifying conductive hearing loss associated with middle
      ear pathology. The consistency and accuracy of these results could be considered
      in additional studies.

PMID- 20151886
TI  - Music perception of cochlear implant users: a questionnaire, and its implications
      for a music training program.
AB  - Current research has shown that although adult cochlear implant (CI) users
      generally find music to be less enjoyable following implantation, training may
      help some recipients to improve their music perception. This study developed and
      administered a questionnaire (The University of Canterbury Music Listening
      Questionnaire: UCMLQ), to collect information which could then be used to develop
      such a music training program (MTP). One hundred adult recipients completed the
      UCMLQ. Results showed that respondents generally found music to be less enjoyable
      post-implantation, and thought that music did not sound as they would expect it
      to sound to a person with normal hearing. However, it was reported that music
      listening could be enhanced by controlling the listening environment, being
      selective about the music chosen, and using a contralateral HA. The preferred
      logistics for a MTP were 30-minute sessions, 2-3 times per week, using a DVD
      format. The program should focus on improving recipients' ability to recognize
      tunes, and encompass a wide range of musical styles. The findings support the
      development of a MTP for CI users to better enable them to enjoy and appreciate
      music, and to maximize their potential with current technology.

PMID- 20151887
TI  - The effect of rate stress on the auditory brainstem response in autism: a
      preliminary report.
AB  - Efforts to correlate peripheral neurophysiologic function with perceptional
      deficits seen in autistic disorder (AD) have resulted in mixed findings,
      reflecting the high degree of heterogeneity observed in these individuals. We
      used the auditory brainstem response to study the effect of stress (high click
      presentation rate) on the auditory system in 20 children with AD (7-13 years) and
      20 age-matched typically developing (TD) children. We report latency
      prolongations in children with AD vs. TD at waves I, III, and V that differed by
      ear of presentation: overall, left ear showed significant prolongations by group
      while right ear did not. The 'stressed' condition produced prolongations for both
      groups at each wave. At wave V, children with AD showed significant prolongations
      vs. TD, particularly for the right ear. For children with AD, wave V latency
      prolongations corresponded to language outcome as measured by VIQ, with longer
      prolongations associating with lower VIQ. Preliminary results provide evidence
      for reduced synaptic efficiency in auditory pathways in children with AD, which
      may form the neural bases for sensory reactivity and language impairment.

PMID- 20151929
TI  - Telehealth in audiology: the need and potential to reach underserved communities.
AB  - Permanent hearing loss is a leading global health care burden, with 1 in 10
      people affected to a mild or greater degree. A shortage of trained healthcare
      professionals and associated infrastructure and resource limitations mean that
      hearing health services are unavailable to the majority of the world population.
      Utilizing information and communication technology in hearing health care, or
      tele-audiology, combined with automation offer unique opportunities for improved
      clinical care, widespread access to services, and more cost-effective and
      sustainable hearing health care. Tele-audiology demonstrates significant
      potential in areas such as education and training of hearing health care
      professionals, paraprofessionals, parents, and adults with hearing disorders;
      screening for auditory disorders; diagnosis of hearing loss; and intervention
      services. Global connectivity is rapidly growing with increasingly widespread
      distribution into underserved communities where audiological services may be
      facilitated through telehealth models. Although many questions related to aspects
      such as quality control, licensure, jurisdictional responsibility, certification
      and reimbursement still need to be addressed; no alternative strategy can
      currently offer the same potential reach for impacting the global burden of
      hearing loss in the near and foreseeable future.

PMID- 20151930
TI  - Development of a new method for deriving initial fittings for hearing aids with
      multi-channel compression: CAMEQ2-HF.
AB  - Moore et al (1999b) described a procedure, CAMEQ, for the initial fitting of
      multi-channel compression hearing aids. The procedure was derived using a model
      of loudness perception for impaired hearing. We describe here the development of
      a new fitting method, CAMEQ2-HF, which differs from CAMEQ in the following ways:
      (1) CAMEQ2-HF gives recommended gains for centre frequencies up to 10 kHz,
      whereas the upper limit for CAMEQ is 6 kHz; (2) CAMEQ is based on the assumption
      that the hearing aid user faces the person they wish to hear and uses a free
      field-to-eardrum transfer function for frontal incidence. CAMEQ2-HF is based on
      the assumption that the user may wish to hear sounds from many directions, and
      uses a diffuse-field-to-eardrum transfer function; (3) CAMEQ2-HF is based on an
      improved loudness model for impaired hearing; (4) CAMEQ2-HF is based on recent
      wideband measurements of the average spectrum of speech.

PMID- 20151931
TI  - Deterioration of cortical responses to amplitude modulations of low-frequency
      carriers after high-frequency cochlear lesion in guinea pigs.
AB  - Temporal modulation transfer function (TMTF) is one of the most common methods
      for evaluating temporal acuity in the auditory system. In this experiment, we
      recorded cortical responses to amplitude modulation of tone carriers from
      implanted electrodes in guinea pigs to generate TMTFs by calculating the response
      amplitude changes as a function of modulation frequencies (Mfs). High-frequency
      hearing loss above 8 kHz was established using tone overstimulation (12 kHz, 110
      dB SPL for 30 hours). The impact of this acoustic trauma on temporal resolution
      in the low-frequency range (below and at 8 kHz) was evaluated with the repeated
      tests of TMTFs until eight weeks post trauma. Deterioration in temporal
      resolution was found to develop over time, especially at 2 kHz, which was
      indicated by the decrease in -3 dB cutoffs in TMTFs and by the overall decrease
      in the AM response amplitude. Potential mechanisms that may underlie this off
      channel affect are discussed.

PMID- 20151932
TI  - Measuring real-ear signal-to-noise ratio: application to directional hearing
      aids.
AB  - Due to individual characteristics such as head size, earmould type, and earmould
      venting, the directional benefit that an individual will obtain from a hearing
      aid cannot be predicted from average data. It is therefore desirable to measure
      real ear directional benefit. This paper demonstrates a method to measure real
      ear hearing aid directivity based on a general approach to measure the broadband
      output signal-to-noise ratio of a hearing aid. Errors arising from non-linearity
      were tested in simulation and found to be low for typical hearing aid compression
      ratios. Next, the efficacy of the method to estimate directional benefit was
      demonstrated on KEMAR. Finally the variability of directional benefit was
      explored in real-ears. Significant differences in signal-to-noise ratio between
      directional and omnidirectional microphone settings were demonstrated at most
      azimuths. Articulation-Index-weighted directional benefit varied by more than 7
      dB across ears at some azimuths. Such individual variation in directional benefit
      has implications when fitting hearing aids: it should not be assumed that all
      users will receive similar directional benefit from the same hearing aid.

PMID- 20151933
TI  - Hemispheric laterality assessment with dichotic digits testing in dyslexia and
      auditory processing disorder.
AB  - One of the widely used tests to evaluate functional asymmetry of cerebral
      hemispheres is the dichotic listening test with the usually prevailing right ear
      advantage. The current study aims at assessing hemispheric laterality in an adult
      sample of individuals with dyslexia, with auditory processing disorder (APD), and
      adults experiencing comorbidity of the two mentioned disorders against a control
      group with normal hearing and absence of learning disabilities. Results exhibit a
      right hemispheric dominance for the control and APD group, a left hemispheric
      dominance for the group diagnosed with both dyslexia and APD, and absence of
      dominance for the dyslexia group. Assessment of laterality was repeatable and
      produced stable results, indicating a true deficit. A component of auditory
      processing, specifically the auditory performance in competing acoustic signals,
      seems to be deficient in all three groups, and laterality of hemispheric
      functions influenced at least for auditory-language stimuli in the two of the
      three groups, one being adults with dyslexia and the other being adults with
      comorbidity of dyslexia and APD.

PMID- 20151936
TI  - Could a wait and see policy be justified in T3/4 rectal cancers after chemo
      radiotherapy?
AB  - Chemoradiotherapy (CRT) followed by total mesorectal excision is the standard
      when MRI staging demonstrates threatened surgical margins in locally advanced
      rectal cancer (LARC). Interest in non-surgical management of LARC as an
      alternative to a resection has been provoked by published excellent long-term
      outcomes of patients who achieve clinical complete responses (cCR) after CRT. The
      present retrospective study aimed to determine whether similar rates of local
      disease control are seen in a UK cancer centre in patients with T3-4 tumours, who
      obtained a cCR after preoperative CRT, but did not undergo surgery. METHOD: The
      outcome and treatment details of 266 patients who underwent CRT for clinically
      staged T3-4 rectal adenocarcinomas between 1993 and 2005 were reviewed. RESULTS:
      Fifty-eight patients did not proceed to surgery, 10 of whom were identified as
      having a cCR. Six of these 10 patients subsequently developed intrapelvic
      recurrent disease with a median time to local progression of 20 months. Local
      relapse preceded the development of metastatic disease or occurred
      simultaneously. No patients underwent salvage resection. CONCLUSION: CRT alone in
      cT3/T4 rectal cancers has a high rate of local relapse even after cCR. Delaying
      or avoiding surgery might be appropriate for cT1 or cT2 tumours, or elderly and
      frail patients with co-morbidity, but these results do not support the current
      uncritical move to extrapolate this approach to all surgically fit patients with
      rectal cancer.

PMID- 20151937
TI  - Trends in survival of patients diagnosed with male genital cancers in the Nordic
      countries 1964-2003 followed up until the end of 2006.
AB  - BACKGROUND: Prostate, testicular and penile cancer constitute about one-third of
      the cancer incidence burden among Nordic males, but less than one-fifth of the
      corresponding mortality. The aim of this study is to describe and interpret
      trends in relative survival and excess mortality in the five Nordic populations.
      MATERIAL AND METHODS: Age-standardised incidence and mortality rates, 5-year
      relative survival, and excess mortality rates for varying follow-up periods are
      presented, as are age-specific 5-year relative survival by country, sex and 5
      year diagnostic period. RESULTS: The vast majority of male genital cancer
      incident cases and deaths are prostate cancers, with 5-year and 10-year survival
      trends resembling the diagnostic-led increasing incidence over the past 25 years.
      Five-year prostate cancer survival is estimated at 53% in Denmark compared to 78%
      or above in the other Nordic populations for patients diagnosed 1999-2003. Excess
      mortality has declined over time, with Denmark having a greater excess of deaths
      compared to the other countries, irrespective of time of diagnosis. Concomitant
      with the declines in testicular cancer mortality, testicular cancer survival has
      increased since the 1970s in each Nordic country. Men diagnosed with testicular
      cancer in recent decades have had, on average, a continually better prognosis
      with time, with relative 5-year survival for patients diagnosed 1999-2003 ranging
      from 88% in Finland to 94% in Sweden. For the few patients diagnosed with cancer
      of the penis and other male genital organs, survival trends have been rather
      stable over time, with recent 5-year relative survival estimates ranging from 62%
      in Finland to 80% in Norway. CONCLUSIONS: There are intriguing country-specific
      and temporal variations in male genital cancer survival in the Nordic countries.
      Prognosis varies widely by cancer site and relates to both changing diagnostic
      and clinical practices. The increasing PSA detection and biopsy makes
      interpretation of the prostate cancer survival trends particularly difficult.

PMID- 20151938
TI  - BRCA1 gene mutations may explain more than 80% of excess number of ovarian cancer
      cases after breast cancer - a population based study from the Western Sweden
      Health Care region.
AB  - AIM: In a previous cohort study, we showed that there was a significant variation
      in the frequency of ovarian cancer after having breast cancer in Sweden, with the
      highest risk occuring in the Western region. The present study aimed to evaluate
      whether the high prevalence of the founder mutation BRCA1 3171ins5 may explain
      the excess number of ovarian cancer. METHOD: Among more than 26 000 women with
      breast cancer in the Western Swedish Health Care Region, 159 cases were
      subsequently diagnosed with ovarian cancer, whereas the expected number was 96.
      Archived tissue material was analysed for six common Scandinavian BRCA1 and BRCA2
      gene mutations. RESULTS: The excess number of cases was 63 (95% CI 47-77), based
      on person-years at risk and national incidence rates of ovarian cancer. A BRCA1
      gene mutation was detected in 33 cases corresponding to 52% of the excess number.
      The founder mutation, BRCA1 3171ins5, was detected in 44% of the excess number.
      The identified mutations decreased from 45% in women less than 50 years of age at
      follow-up to 14% at 60+ years at follow-up. There was no obvious decrease in
      mutation frequency by excess numbers with age. Age at follow-up and first-degree
      relatives with breast and/or ovarian cancer were the best predictors of a
      mutation in this material. CONCLUSION: The founder mutation, BRCA1 3171ins5,
      explains the excess of ovarian cancer after breast cancer in the region. From the
      relative frequency of the studied mutations found at the cancer genetic
      counselling clinic, it is estimated that BRCA1 gene mutations are associated with
      about 80-85% of the excess cases. This means that a negative screening for these
      mutations in similar cases may have a predictive value and could strongly reduce
      the risk of ovarian cancer in relatives.

PMID- 20151940
TI  - Effects of combination of zinc and vitamin A supplementation on serum fasting
      blood sugar, insulin, apoprotein B and apoprotein A-I in patients with type I
      diabetes.
AB  - BACKGROUND AND AIM: There is accumulating evidence that shows the metabolism of
      zinc and vitamin A are altered in diabetes mellitus type I (DMTI), thus the
      present study was conducted to evaluate the effects of combination of zinc and
      vitamin A supplementation on serum fasting blood sugar (FBS), insulin, apoprotein
      B and apoprotein A-I in patients with DMTI. DESIGN: Forty-eight, 7-year-old to 20
      year-old patients with at least 2 years of DMTI history, without any metabolic
      condition or medicine intake with insulin treatment, participated in a randomized
      double-blind clinical trial for 12 weeks. They were divided into zinc and vitamin
      A (VAZ)-supplemented (10 mg elemental zinc per day and one-half of a 25,000 IU
      vitamin A tablet every other day) and/or placebo groups after matching for sex,
      age and DMTI duration. Nutrient intake was estimated using 24 h recall and was
      analyzed by food processor program. Serum apoproteins B and A-I, FBS and insulin
      levels were determined at the beginning and end of the trial. RESULTS: There was
      significant increase in apoprotein A-I (P < 0.0001) and a significant decrease in
      apoprotein B (P < 0.0001) and apoprotein B/apoprotein A-I ratio (P < 0.0001) at
      the end of the study compared with baseline values in the VAZ group but
      apoprotein A-I had a significant increase (P < 0.0001) and the apoprotein
      B/apoprotein A-I ratio had a significant decrease (P = 0.02) at the end of study
      in the VAZ group compared with the control group CONCLUSION: It seems that
      combined zinc and vitamin A supplementation can improve serum apoprotein A-I,
      apoprotein B and the apoprotein B/apoprotein A-I ratio in patients with DMTI.

PMID- 20151941
TI  - Targeted delivery of anti-cancer growth inhibitory peptides derived from human
      alpha-fetoprotein: review of an International Multi-Center Collaborative Study.
AB  - The alpha-fetoprotein derived growth inhibitory peptide (GIP) is a 34-amino acid
      peptide composed of three biologically active subfragments. GIP-34 and its three
      constituent segments have been synthesized, purified, and studied for biological
      activity. The GIP-34 and GIP-8 have been characterized as anticancer therapeutic
      peptides. An multicenter study was initiated to elucidate the means by which
      these peptide drugs could be targeted to tumor cells. The study first established
      which cancer types were specifically targeted by the GIP peptides in both in
      vitro and in vivo investigations. It was next demonstrated that radiolabeled
      peptide ((125)I GIP-34) is specifically localized to rodent breast tumors at 24 h
      post-injection. The radionuclide studies also provided evidence for a proposed
      cell surface receptor; this was confirmed in a further study using fluorescent
      labeled GIP-nanobeads which localized at the plasma membrane of MCF-7 breast
      cancer cells. Finally, it was readily demonstrated that GIP conjugated to either
      fluorescein or doxorubicin (DOX) underwent tumor cell uptake; subsequently, DOX
      GIP conjugates induced cytotoxic cell destruction indicating the utility of GIP
      segments as cancer therapeutic agents. Following a discussion of the preceding
      results, a candidate cell surface receptor family was proposed which correlated
      with previous published reports for a putative AFP/GIP receptor.

PMID- 20151942
TI  - Preparation of pH-dependent modified-release pellets of urapidil to improve its
      bioavailability.
AB  - OBJECTIVE: Modified-release pellets containing urapidil were developed and its in
      vivo bioavailability was investigated. METHODS: Lactose and MCC were used as the
      main fillers to prepare drug-layer pellets by the powder layering method using
      centrifugal granulation, and coated in a fluidized bed coater. Pellets with
      different drug release characteristics were prepared with a methacrylic acid
      copolymer aqueous dispersion. RESULTS: Using commercial German capsules as the
      reference (R), two coating formulations were selected for tests after
      optimization: pH-dependent pellets with a ratio of Eudragit((r)) NE30D/L30D55 of
      10:1, a 3% coating level (T(1)), and pH-independent pellets with a Eudragit((r))
      NE30D coating level (T(2)) of 3.5%. The bioavailability of the pellets (T(1),
      T(2), containing 30 mg urapidil) was determined in six healthy subjects after
      oral administration of a single dose, for a period of three weeks, in the form of
      a crossover design with a wash-out period of one week. The plasma concentrations
      of urapidil were determined by HPLC with UV detection. The C(max) (maximum
      concentration), T(max), and MRT of T(1) were 311.7 ng/mL, 5.3 h and 8.3 h,
      respectively. T(1) was bioequivalent to R, with a relative bioavailability
      110.9%. The C(max) and T(max), of T(2) were 105.3 ng/mL and 13.3 h, respectively,
      and the relative bioavailability was 72.7%. CONCLUSION: The pH-dependent urapidil
      pellets have a high bioavailability.

PMID- 20151943
TI  - Dopaminergic modulation of the neuron activity in the cerebral cortex of the
      wakeful animal.
AB  - Specific effects of the dopamine synaptic transmission modulator on the activity
      of sensomotor cortical neurons in a wakeful animal, performing a conditioned
      reflex are discussed. First, specific responses in the neocortical neurons after
      application of glutamate agonists and antagonists and gamma aminobutyric acid are
      described and then the effect of dopamine, its agonists and antagonists and
      amantadine, a dopamine releaser, on the background and induced pulse activities
      in the cortical neurons, as well as on specific characteristics of conditioned
      reflex motor responses, such as latency and intensity are analyzed in detail.

PMID- 20151944
TI  - [Postthrombotic syndrome--not an unchangeable syndrome].

PMID- 20151946
TI  - New mutation in the CYLD gene within a family with Brooke-Spiegler syndrome.
AB  - Brooke-Spiegler syndrome is a rare, autosomal dominant disease characterized by
      multiple skin appendage tumors caused by various mutations in the CYLD gene on
      chromosome 16q12-q13. We describe a family, in which we performed a molecular
      genetic examination and found a new mutation in exon 19 in the CYLD gene leading
      to a frameshift. It is important to be aware of this syndrome and its
      pathogenesis as its phenotypic features can vary so that apparently different
      diseases are caused by the same genetic defect. In addition, there may be
      malignant transformation of the generally benign tumors, so that a timely
      diagnosis is essential for appropriate monitoring and therapy.

PMID- 20151947
TI  - FoxO1 - the key for the pathogenesis and therapy of acne?
AB  - Five main factors play a pivotal role in the pathogenesis of acne: androgen
      dependence, follicular retention hyperkeratosis, increased sebaceous lipogenesis,
      increased colonization with P. acnes, and inflammatory events. This paper offers
      a solution for the pathogenesis of acne and explains all major pathogenic factors
      at the genomic level by a relative deficiency of the nuclear transcription factor
      FoxO1. Nuclear FoxO1 suppresses androgen receptor, other important nuclear
      receptors and key genes of cell proliferation, lipid biosynthesis and
      inflammatory cytokines. Elevated growth factors during puberty and persistent
      growth factor signals due to Western life style stimulate the export of FoxO1 out
      of the nucleus into the cytoplasm via activation of the phos-phoinositide-3
      kinase (PI3K)/Akt pathway. By this mechanism, genes and nuclear receptors
      involved in acne are derepressed leading to increased androgen receptor-mediated
      signal transduction, increased cell proliferation of androgen-dependent cells,
      induction of sebaceous lipogenesis and upregulation of Toll-like-receptor-2
      dependent inflammatory cytokines. All known acne-inducing factors exert their
      action by reduction of nuclear FoxO1 levels. In contrast, retinoids, antibiotics
      and dietary intervention will increase the nuclear content of FoxO1, thereby
      normalizing increased transcription of genes involved in acne. Various receptor
      mediated growth factor signals are integrated at the level of PI3K/Akt activation
      which finally results in nuclear FoxO1 deficiency.

PMID- 20151948
TI  - Uncombable hair and atopic dermatitis in a case of trichodento-osseous syndrome.
AB  - The tricho-dento-osseous syndrome is a rare genetic disorder due to a mutation in
      the DLX3 gene on chromosome 17q21. It can affect hair, teeth, bone and nails,
      causing phenotypic variability. We report on an 8-year-old girl with tricho-dento
      osseous syndrome, who presented in our allergy center with severe atopic
      dermatitis. Additional clinical findings included light, kinky hair reminiscent
      of pili trianguli et canaliculi (uncombable hair), enamel hypoplasia and enlarged
      pulp chambers of the molar teeth (taurodontism). A genetic investigation revealed
      a de-novo mutation in the DLX3 gene on chromosome 17q21. Electron microscopic
      examination of the curly hair showed a flattened hair shaft with longitudinal
      grooves.

PMID- 20151949
TI  - [Subcutaneus nodule at the index finger of a 56-years-old female patient. Giant
      cell tumor of the tendon sheath].

PMID- 20151950
TI  - Factors associated with successful establishment of breastfeeding in very preterm
      infants.
AB  - AIM: To describe feeding practices at hospital discharge in relation to
      characteristics of the very preterm infants (VPI) and their mothers. METHODS:
      Design. Prospective hospital-based registration of very preterm infants born with
      a gestational age < or =32 weeks in Denmark during 2004-2008. Subjects. Healthy
      mothers and VPI without diseases causing eating disabilities at discharge.
      RESULTS: A total of 478 VPI were registered. At discharge, 60% were exclusively
      breastfed, 35% were exclusively bottlefed, and 5% were both breast- and bottle
      fed. Mothers of high social class (p = 0.000) and 'not smoking' (p = 0.003) were
      significantly more often breastfeeding their preterm infant(s) at discharge.
      Single births infants tended more often to be breastfed (p = 0.09). Infant age at
      discharge and duration of hospitalization did not influence breastfeeding at
      discharge. Increase in weight z-score from birth to discharge was largest in the
      bottlefeeding-group compared with the breastfeeding-group (p = 0.000) probably as
      a result of feeding practice the last week(s) of hospitalization. CONCLUSION:
      Breastfeeding can successfully be established in very preterm infants. Mothers of
      low social classes, smokers, multiple birth and very preterm infants with low
      weight for age may need extra attention in breastfeeding establishing policies.

PMID- 20151952
TI  - Neonatal renal vein thrombosis and prothrombotic risk.
AB  - A case of extensive deep venous thrombosis in a four a day old infant was
      presented. Unusually this patient was shown to be heterozygous for three
      thrombophilia genes; Factor V Leiden, prothrombin and antithrombin gene
      mutations, the latter being novel. CONCLUSION: There are no randomized controlled
      trials to guide management in deep venous thrombosis in the newborn but knowledge
      of the prothrombotic risk factors may help direct treatment.

PMID- 20151953
TI  - Airway obstruction at time of symptoms prompting use of reliever therapy in
      children with asthma.
AB  - BACKGROUND: In asthma treatment, doses of inhaled corticosteroids are often
      adapted to symptoms and need for bronchodilators. However, in cross-sectional
      studies in emergency room settings, lung function and respiratory symptoms are
      not always concordant. Available longitudinal data are based on written peak flow
      diaries, which are unreliable. Using home spirometry, we studied prospectively
      whether mild respiratory symptoms, prompting reliever therapy are accompanied by
      a clinically relevant drop in lung function in children with asthma. METHODS: For
      8 weeks, children with asthma scored symptoms and measured peak expiratory flow
      (PEF) and forced expiratory volume in 1 sec (FEV(1)) on a home spirometer twice
      daily. Additional measurements were recorded when respiratory symptoms prompted
      them to use bronchodilators. RESULTS: The mean difference between symptom free
      days and at times of symptoms was 6.6% of personal best for PEF (95% CI: 3.2
      10.0; p = 0.0004) and 6.0% of predicted for FEV(1) (95% CI: 3.0-9.0; p = 0.0004).
      There was complete overlap in PEF and FEV(1) distributions between symptom free
      days and at times of symptoms. CONCLUSIONS: Although statistically significant,
      the degree of airway narrowing at times of respiratory symptoms, prompting the
      use of reliever therapy, is highly variable between patients, limiting the
      usefulness of home spirometry to monitor childhood asthma.

PMID- 20151954
TI  - Molecular analysis of the CART gene in overweight and obese Italian children
      using family-based association methods.
AB  - AIM: In our study, we evaluated if CART gene A1475G and DeltaA1457 polymorphisms
      could be associated with obesity. PATIENTS AND METHODS: We recruited 133 Italian
      trios from among 103 (50 males and 53 females) overweight children (mean age 10.5
      years, range 6-14 years; mean BMI 26.1 +/- 3.2 kg/m(2)), and 30 (16 males and 14
      females) obese children (mean age 9.0 years, range 6-11 years; mean BMI 32.3 +/-
      2.0 kg/m(2)). We also selected 187 non-obese unrelated controls. RESULTS: The
      allele frequencies of the A1475G single nucleotide polymorphism (SNP) were
      significantly higher in overweight children (0.07) than in control children
      (0.02) (p = 0.03) and control adults (0.02) (p = 0.02). Moreover, the allele
      frequencies were significantly different between obese children (0.08) and
      control children (0.02) (p = 0.03), and between obese children (0.08) and control
      adults (0.02) (p = 0.02). The DeltaA1457 SNP showed no significant association
      with overweight/obesity. TDT statistic revealed a preferential transmission of
      the 1475G allele from heterozygous parents to overweight children (p < 0.01) and
      to obese children (p < 0.05). No statistically significant excess transmission of
      the DeltaA1457 allele was found. CONCLUSION: Our results supported the hypothesis
      that inherited variations of the CART gene could influence the development of
      obesity also in Italian children.

PMID- 20151955
TI  - Association between nitrous oxide and the incidence of postoperative nausea and
      vomiting in adults: a systematic review and meta-analysis.
AB  - Some, but not all studies have suggested intra-operative use of nitrous oxide is
      correlated with postoperative nausea and vomiting. We performed a meta-analysis
      of randomised controlled trials to compare the incidence of nausea and vomiting
      in adults following general anaesthesia with or without nitrous oxide. We
      retrieved 30 studies (incorporating 33 separate trials) that investigated a
      'nitrous oxide group' (total 2297 patients) vs a 'no-nitrous oxide group' (2301
      patients). Omitting nitrous oxide significantly reduced postoperative nausea and
      vomiting (pooled relative risk 0.80, 95% CI 0.71-0.90, p = 0.0003). However, the
      absolute incidence of nausea and vomiting was high in both the nitrous oxide and
      no-nitrous oxide groups (33% vs 27%, respectively). In subgroup analysis, the
      maximal risk reduction was obtained in female patients (pooled relative risk
      0.76, 95% CI 0.60-0.96). When nitrous oxide was used in combination with
      propofol, the antiemetic effect of the latter appeared to compensate the
      emetogenic effect of nitrous oxide (pooled relative risk 0.94, 95% CI 0.77-1.15).
      We conclude that avoiding nitrous oxide does reduce the risk of postoperative
      nausea and vomiting, especially in women, but the overall impact is modest.

PMID- 20151956
TI  - The effects of mild induced hypothermia on the myocardium: a systematic review.
AB  - Mild induced hypothermia improves neurological outcome and reduces mortality
      among initially comatose survivors of out-of-hospital cardiac arrest. Similar
      pathological processes occur in the heart and the brain, namely ischaemia
      followed by reperfusion injury. Animal data indicate that mild induced
      hypothermia results in improved myocardial salvage, reduced infarct size, reduced
      left ventricular remodelling and better long-term left ventricular function.
      Several small human studies suggest that infarct size may be reduced by mild
      induced hypothermia, although this has not reached significance in any human
      study to date. There are variable reports of harm to the myocardium caused by
      mild induced hypothermia, including reduced myocardial contractility and cardiac
      output, electrocardiographic changes and arrhythmias, especially bradycardia.
      These harmful effects are reversible with rewarming.

PMID- 20151957
TI  - 'To thine own self be true': on the loss of integrity as a kind of suffering.
AB  - One of the requirements in the Dutch regulation for euthanasia and assisted
      suicide is that the doctor must be satisfied 'that the patient's suffering is
      unbearable, and that there is no prospect of improvement.' In the notorious
      Chabot case, a psychiatrist assisted a 50 year old woman in suicide, although she
      did not suffer from any somatic disease, nor strictly speaking from any
      psychiatric condition. In Seduced by Death, Herbert Hendin concluded that
      apparently the Dutch regulation now allows physicians to assist anyone in suicide
      simply because he or she is unhappy. In this paper, I reject Hendin's conclusion
      and in particular his description of Mrs Boomsma as someone who was 'simply
      unhappy.' After a detailed narration of her lifestory, I turn to the American
      philosopher Harry Frankfurt's account of volitional incapacity and love for a
      more accurate characterization of her suffering. Having been through what she
      had, she could only go on living as another person than the one she had been when
      she was a happy mother. That would have violated her integrity, and that she
      could not bring herself to do.

PMID- 20151958
TI  - The dapoxetine paradox.

PMID- 20151959
TI  - Changes in symptoms of renal cell carcinoma over four decades.
AB  - OBJECTIVE: To determine whether there has been a change in typical symptoms of
      renal cell carcinoma (RCC), by evaluating the symptoms of patients diagnosed
      during four decades, as although the increasing incidence of a diagnosis of
      incidental RCC has been widely reported, the change in other symptoms has not.
      PATIENTS AND METHODS: The study included RCC cases diagnosed in the Pirkanmaa
      Hospital District between 1964 and 1997. The original medical records of 970
      patients with 982 RCC tumours were analysed. Primary symptoms were recorded and
      changes were analysed in three groups, i.e. diagnoses made before 1980, in the
      1980s and in the 1990s. Symptoms were also analysed according to stage, tumour
      class, gender and age. RESULTS: The incidence of haematuria (P < 0.01) and an
      increased erythrocyte sedimentation rate (P < 0.001) decreased, but there was no
      change in other symptoms. Incidental diagnoses increased from 12% to 19% (P <
      0.01). Less chronic or systemic symptoms were noted more recently. Stage and
      tumour class were highly correlated with symptoms: systemic symptoms increased
      (24% in stage I to 72% in stage IV, a highly statistically significant increase)
      and asymptomatic tumours became rarer (27% in stage I to 8% in stage IV, again a
      highly significant increase) with increasing stage. Haematuria was more common in
      male patients, anaemia and flank pain in women. Elderly patients were more often
      asymptomatic than younger patients, with 70-79-year-olds being the least
      symptomatic. CONCLUSIONS: Incidental cases of RCC have recently become more
      common. Haematuria, hypersedimentation, chronic and systemic symptoms have
      decreased. Stage, tumour class, gender and age are correlated with symptoms.

PMID- 20151960
TI  - Comparison of transfusion requirements between open and robotic-assisted
      laparoscopic radical prostatectomy.
AB  - OBJECTIVE: To determine whether robotic-assisted laparoscopic radical
      prostatectomy (RALP) is associated with a lower transfusion rate than radical
      retropubic prostatectomy (RRP). PATIENTS AND METHODS: In this cohort study, we
      evaluated 1244 consecutive patients who underwent RALP (830) or RRP (414) between
      June 2003 and July 2006. Demographics, clinical characteristics, pathology, blood
      loss and transfusion data were collected prospectively. Groups were compared for
      baseline characteristics, blood loss, change in haematocrit and transfusion using
      univariate statistics, and an exploratory multivariate model was developed.
      RESULTS: RALP was associated with lower blood loss (median 100 vs 450 mL, P <
      0.001) and a smaller change in haematocrit (median 7% vs 10%, P < 0.001) than
      RRP. Although both groups had low transfusion rates, the RALP group required
      fewer transfusions than the RRP group (0.8% vs 3.4%, P= 0.002). On univariate
      analysis, surgical approach (RRP vs RALP), estimated blood loss >=500 mL and
      change in haematocrit >=10% were the only the significant predictors of
      transfusion. In the exploratory multivariate model RALP was the only significant
      predictor of reduced need for transfusion, with an odds ratio of 0.23 (95%
      confidence interval 0.09-0.58; P= 0.002). CONCLUSIONS: This study shows that RALP
      is associated not only with less blood loss and a smaller decrease in
      haematocrit, but also a decreased need for transfusion.

PMID- 20151961
TI  - Association of statin and nonsteroidal anti-inflammatory drug use with prostate
      cancer outcomes: results from CaPSURE.
AB  - OBJECTIVE: To determine whether 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (statins) and nonsteroidal anti-inflammatory drugs (NSAIDs) are
      associated with the risk of prostate cancer and improved survival in men with
      prostate cancer. PATIENTS AND METHODS: We retrospectively examined the
      association between NSAID and statin use among 7042 men who underwent radical
      prostatectomy (RP, 4611) or radiotherapy (RT, 2431) for prostate cancer between
      1990 and 2003 identified in the Cancer of the Prostate Strategic Urologic
      Research Endeavor (CaPSURE), a primarily community-based national prostate cancer
      registry. We compared clinical and sociodemographic variables by statin and NSAID
      use, using chi-square tests and multinomial logistic regression. We examined
      associations between medications and comorbid illness with mortality using
      unadjusted and adjusted Cox proportional hazard models. RESULTS: The median
      (range) follow-up from treatment was 4 (0-16) years. In multivariate survival
      analysis, statin 'ever-use' was associated with a reduced risk of all-cause
      mortality (ACM) after RP (hazard ratio, HR, 0.35, 95% confidence interval, CI,
      0.21-0.58) and RT (0.59, 0.37-0.94). NSAID ever-use was also associated with a
      reduced risk of ACM after RP (HR 0.47, 95% CI 0.30-0.75) and RT (0.39, 0.25
      0.59). CONCLUSIONS: In a population of men with prostate cancer, statin and NSAID
      ever-use were associated with a reduced risk of ACM. Our study highlights the
      importance of multidisciplinary survivorship care for men with prostate cancer.

PMID- 20151962
TI  - Voiding effects mediated by alpha2-adrenoceptors in the anaesthetized male rat.
AB  - OBJECTIVE: To study the role of alpha(2)-adrenoceptors (alpha(2)-AR) in
      micturition of anaesthetized male rats, with specific focus on the effects on the
      electrical activity (by electromyography, EMG) of the rhabdosphincter, and actual
      urinary flow rate, as the effects mediated by alpha(2)-ARs on sphincter activity
      and urethral pressures have not been established. MATERIALS AND METHODS: Adult
      anaesthetized male Noble rats were used; intravesical pressure, rhabdosphincter
      EMG and urinary flow rate from the distal urethra were recorded. After baseline
      recordings, an alpha(2)-AR agonist (dexmedetomidine, DEX) or alpha(2)-AR
      antagonist (atipamezole), were injected intravenously. RESULTS: DEX treatment
      significantly decreased the maximum bladder pressure and urinary flow rate, and
      the amplitude of rhabdosphincter EMG was significantly reduced. Intraluminal
      pressure high-frequency oscillations, usually observed during rat voiding were
      abolished. The effects of DEX were fully reversed within 31 min. Atipamezole
      treatment significantly increased actual urinary flow rates and rhabdosphincter
      EMG amplitude, but the number of times flow was interrupted was increased during
      the voiding cycle, leading to increased overall micturition time. CONCLUSION:
      Stimulation and blockade of alpha(2)-ARs have a significant effect on lower
      urinary tract function. If the data from this rat model are also valid in humans,
      a study of the effects of atipamezole on urethral sphincter activity and urethral
      pressures in humans would be of interest, and might show therapeutic potential of
      the drug.

PMID- 20151963
TI  - Racial and ethnic variation in health resource use and cost for prostate cancer.
AB  - OBJECTIVE: To analyse the racial and ethnic variation in health resource use
      (HRU) and direct medical care (DMC) cost in elderly men with prostate cancer.
      PATIENTS AND METHODS: This was a retrospective case-control study using the
      linked Surveillance, Epidemiology, and End Results Medicare database. Patients
      with prostate cancer diagnosed between 1995 and 1998 (50 147 men) were identified
      and followed retrospectively for 1 year before and 5 years after the diagnosis.
      Phase-specific HRU and DMC costs were compared between racial and ethnic groups
      using parametric and nonparametric analysis. To compute the incremental cost of
      prostate cancer, a matched non-cancer control group was extracted from Medicare
      database. Poisson and general linear models (log-link) were used to identify the
      association of race and ethnicity with HRU and DMC cost, after controlling for
      potentially influential clinical and demographic covariates. RESULTS: The African
      American group was more likely to have emergency-room visits (odds ratio 1.19,
      95% confidence interval 1.12-1.28) and less likely to have outpatient visits
      (0.96, 0.96-0.97) than whites. However, the Hispanic group was more likely to
      have inpatient and outpatient visits (odds ratio 0.88, 0.83-0.91; and 0.93, 0.91
      0.95) than whites. Adjusted DMC cost showed racial and ethnic variation in all
      phases except the treatment and terminal phases. Factors associated with DMC cost
      varied among racial and ethnic groups. CONCLUSION: The incremental burden of
      prostate cancer remains significant in the long term. Overall, the cost of
      prostate cancer care was higher among African-American men than white and
      Hispanic men. This indicates the need for further research on care-level factors
      to comprehend the racial and ethnic disparity in HRU and cost.

PMID- 20151964
TI  - Natural history and long-term testicular growth of acquired undescended testis
      after spontaneous descent or pubertal orchidopexy.
AB  - OBJECTIVE: To assess prospectively the natural history and long-term testicular
      growth of acquired undescended testis (UDT) after spontaneous descent or pubertal
      orchidopexy in case of nondescent. PATIENTS AND METHODS: From 1996 until 2008,
      391 boys with 464 acquired UDT were included in the study. In accordance with
      Dutch consensus on non-scrotal testes, spontaneous descent at puberty was
      awaited; if this did not take place, orchidopexy was performed at puberty.
      Acquired UDT was defined as a testis previously residing in the scrotum that can
      no longer be manipulated into a stable scrotal (high scrotal) or nonscrotal
      (inguinal, impalpable) position. After referral, testis position, testis volume
      and puberty stage were monitored annually until adolescence. Testis volume was
      assessed using an orchidometer and compared with the Dutch standard. All
      investigations were carried out by the same physician (W.H.). Of these boys, 84
      (mean age 12.9 years, range 6.4-21.3) were also clinically assessed by a second
      physician (J.G.), unaware of the results of the first examination. In addition,
      these boys were assessed with testicular ultrasonography, carried out by both
      physicians. RESULTS: Currently the mean (range) follow-up is 4.7 (0.1-12.0)
      years, and 253 acquired UDT have reached the scrotum. In 196 of these 253 cases
      (77.5%), there was spontaneous descent at puberty (mean age at descent 12.9
      years, range 9.8-16.9); in the other 57 cases (22.5%), pubertal orchidopexy was
      required due to nondescent; five cases required orchidectomy. Of the 494 testis
      volume measurements after spontaneous descent, 458 (92.7%) were at >=10th centile
      for age, of which 311 (63.0%) were >=50th centile, and 107 (21.7%) >=90th
      centile. After pubertal orchidopexy for nondescent, of the 85 measurements, 79
      (92.9%) were at >=10th centile, 53 (62.4%) >=50th centile and 12 (14.1%) >=90th
      centile. In unilateral cases, after spontaneous descent 174 of the 294 (59.2%)
      retained testes were found to be smaller than their counterpart and 90 of 294
      (30.6%) were equal in size. After pubertal orchidopexy in unilateral cases, 40 of
      the 51 (78.4%) testes were smaller, and nine (17.6%) were equal in size. There
      was a strong correlation between both investigators for the measurement of
      testicular volume by orchidometer, and for the main investigator (W.H.) between
      his measurements by ultrasonography and the Prader orchidometer. CONCLUSION:
      Acquired UDT has a 77.5% tendency of spontaneous descent at puberty. In nearly
      all cases, after spontaneous descent as well as after pubertal orchidopexy, long
      term testicular growth is within the normal range.

PMID- 20151965
TI  - Questioning the wisdom of tubeless percutaneous nephrolithotomy (PCNL): a
      prospective randomized controlled study of early tube removal vs tubeless PCNL.
AB  - OBJECTIVE: To establish the efficacy of early removal of a nephrostomy tube after
      percutaneous nephrolithotomy (PCNL), to challenge the wisdom of tubeless PCNL, as
      we hypothesized that it would result in a shorter hospital stay, comparable
      benefit and safety, while maintaining the option of check nephroscopy ensuring
      far superior stone clearance. PATIENTS AND METHODS: In all, 22 patients were
      prospectively randomized equally into two groups, group 1 (early nephrostomy
      removal) or group 2 (tubeless) during a 1-month study period. Inclusion criteria
      for the study were: a simple stone of <3 cm, no significant bleeding, no
      perforation, single-tract access and 'on-table' complete stone clearance. In
      group 1, a 20 F nephrostomy, 6 F retrograde ureteric catheter and a Foley
      catheter were used, while in group 2 only a 6 F retrograde ureteric catheter and
      Foley catheter were placed at the end of the procedure. Computed tomography (CT)
      with no contrast medium was done on the first morning after surgery before
      removing all catheters/tubes, and patients discharged subsequently. The variables
      assessed were stone clearance, hospital stay, analgesic requirement,
      postoperative complications and auxiliary procedures. RESULTS: The mean (SD)
      stone bulk was similar between the groups, at 2737 (946.9) and 2934.2 (2090.7)
      uL, respectively. Despite an on-table complete clearance, clearance assessed by
      CT was nine of 11 vs eight of 11 in groups 1 and 2, respectively. CT showed a 6
      mm stone in one patient in group 1, while the remaining patients had stones of <4
      mm. The mean (SD) analgesic requirement, haemoglobin decrease, urine leak and
      hospital stay in the two groups were 72.7 (51.8) vs 68.2 (46.2) mg of tramadol
      (P= 0.25), 1.6 (0.7) vs 1.6 (0.9) g/dL (P= 0.39), 13.9 (6.3) vs 7.1 (14.2) h (P=
      0.018) and 72.8 (2.1) vs 70.2 (18.5) h (P= 0.09), respectively. Complications
      noted were early haematuria in none vs three (P= 0.21), urinoma none vs one, and
      fever in two vs one, respectively; one patient in group 1 required a check
      nephroscopy for a residual fragment. Overall clearance including re-treatment was
      10/11 vs eight of 11 (P= 0.009), respectively. CONCLUSION: Early tube removal
      after PCNL results in an equivalent analgesic requirement, decrease in
      haemoglobin and hospital stay as tubeless PCNL. It has a significantly lower
      incidence of early haematuria, better clearance rates and preserves the option of
      check nephroscopy. It can be considered as an accepted standard of care, with the
      preserved advantages of tubeless PCNL.

PMID- 20151966
TI  - Mechanisms of inhibition of human benign prostatic hyperplasia in vitro by the
      luteinizing hormone-releasing hormone antagonist cetrorelix.
AB  - OBJECTIVE: To assess the mechanism by which the luteinizing hormone-releasing
      hormone (LHRH) antagonist cetrorelix exerts its effects in men with benign
      prostatic hyperplasia (BPH), as it produces a long-lasting improvement in lower
      urinary tract symptoms that is only partly accounted for by the transient
      reduction in testosterone levels, and the beneficial results could be due to
      direct inhibitory effects of cetrorelix on the prostate exerted through prostatic
      LHRH receptors. MATERIALS AND METHODS: Using the BPH-1 cell line we evaluated the
      effects of cetrorelix in vitro on the proliferation and the expression of
      receptors for LHRH, epidermal growth factor (EGF), alpha(1A) -adrenergic
      receptor, STAT-3 transcription factor and the response to growth factors insulin
      like growth factor (IGF)-1 and -II and fibroblast growth factor (FGF)-2. RESULTS:
      There was expression of LHRH receptors in the human BPH-1 cell line. Cetrorelix
      had inhibitory effects on the proliferation rate of BPH-1 cells, also reflected
      by the decrease in the expression of the proliferating cell nuclear antigen
      (PCNA). Cetrorelix inhibited the stimulatory effect of the growth factors IGF-I
      and -II and FGF-2 on the proliferation of this line. Cetrorelix also
      downregulated the expression of the receptors for LHRH and EGF, as well as of
      alpha(1A) -adrenergic receptors, and inhibited the activation of the STAT3
      transcription factor. CONCLUSIONS: The results show that in vitro cetrorelix can
      directly inhibit the proliferation rate of the human BPH-1 cell line by
      counteracting growth factors like IGF-I and -II and FGF-2, and downregulating the
      LHRH receptor and alpha-adrenergic receptors, as well as transcription factors.

PMID- 20151967
TI  - External validation of the SEARCH model for predicting aggressive recurrence
      after radical prostatectomy: results from the Duke Prostate Center Database.
AB  - OBJECTIVE: To validate a model previously developed using the Shared Equal Access
      Regional Cancer Hospital (SEARCH) database to predict the risk of aggressive
      recurrence after surgery, defined as a prostate-specific antigen (PSA) doubling
      time (DT) of <9 months, incorporating pathological stage, preoperative PSA level
      and pathological Gleason sum, that had an area under the curve (AUC) of 0.79
      using a cohort of men from the Duke Prostate Center (DPC). PATIENTS AND METHODS:
      Data were included from 1989 men from the DPC database who underwent RP for node
      negative prostate cancer between 1987 and 2003. Of these men, 100 had disease
      recurrence, with a PSADT of <9 months, while 1889 either did not have a
      recurrence but had > or =36 months of follow-up or had a recurrence with a PSADT
      of > or =9 months. We examined the ability of the SEARCH model to predict
      aggressive recurrence within the DPC cohort, and examined the correlation between
      the predicted risk of aggressive recurrence and the actual outcome within DPC.
      RESULTS: The SEARCH model predicted aggressive recurrence within DPC with an AUC
      of 0.82. There was a strong and significant correlation between the predicted
      risk of aggressive recurrence based on the SEARCH tables and the actual outcomes
      within DPC (r= 0.68, P < 0.001), although the model predictions tended to be
      slightly higher than the actual risk. CONCLUSIONS: The SEARCH model to predict
      aggressive recurrence after RP predicted aggressive recurrence in an external
      dataset with a high degree of accuracy. These tables, now validated, can be used
      to help select men for adjuvant therapy and clinical trials.

PMID- 20151968
TI  - Evaluation of fluorodeoxyglucose positron-emission tomography with computed
      tomography for staging of urothelial carcinoma.
AB  - OBJECTIVE: To investigate the role of (18) F-fluorodeoxyglusose positron-emission
      tomography (FDG-PET), combined with computed tomography (CT) and forced diuresis,
      in the staging and follow-up of urothelial carcinoma (UC). PATIENTS AND METHODS:
      We recruited 44 patients with muscle-invasive urothelial bladder cancer (UBC)
      before radical cystectomy (RC), 19 under follow-up after RC and seven after
      systemic chemotherapy. For those who had RC, histopathology was used as the
      reference standard to compare the sensitivity and specificity of FDG-PET/CT and
      standard CT in detecting UBC and pelvic lymph node metastasis. Furthermore, 36
      patients with >= 6 months of follow-up imaging were considered to describe the
      progression of UC and extrapelvic positive FDG-PET/CT images. RESULTS: For the
      detection of primary UBC, FDG-PET/CT was slightly more sensitive than CT (85% vs
      77%) but less specific (25% vs 50%). For the detection of pelvic node metastasis
      FDG-PET/CT was more sensitive than CT (57% vs 33%) with a specificity of 100% for
      both imaging techniques. In 20 patients, extrapelvic FDG-PET/CT images showed
      suspected disease at the first evaluation. UC progressed in nine of the 10
      patients who had synchronous multiple PET-positive retroperitoneal or mediastinal
      lymph nodes, and in only two of the nine with unique hyperactive lesions in the
      lung. FDG-PET/CT also detected a pT1G3 UC of the renal pelvis and all bone
      metastases detected by bone scintigraphy. CONCLUSIONS: FDG-PET/CT could replace
      standard CT and bone scintigraphy in the presurgical staging and monitoring of
      patients with UC after surgery or chemotherapy.

PMID- 20151969
TI  - Development of a scale to assess patient misperceptions about treatment choices
      for localized prostate cancer.
AB  - OBJECTIVES: To develop a questionnaire to assess a patient's knowledge of his
      cancer, understanding of treatment choices, and judgement of his survival (KUJ)
      with and without treatment, as treatment for localized prostate cancer (LPC) can
      lead to urinary, sexual and bowel side-effects and might not improve survival in
      75% of patients. PATIENTS AND METHODS: Although >90% of patients in the USA are
      diagnosed with LPC, approximately 94% of them choose treatment, such that newly
      diagnosed patients need individualized counselling to address misperceptions
      about the management of LPC. The internal consistency of an 18-item KUJ scale was
      evaluated among 184 patients recently diagnosed with LPC at a major urology
      practice. Principal-component analyses were applied for computing a KUJ index.
      Logistic regression modelling was used to identify predictors of the KUJ index.
      RESULTS: Cronbach's alpha for the KUJ scale was 0.76. Nearly half of the patients
      provided incorrect answers to most KUJ items. Of the patients, 68% had an income
      of >US$50,000 and 90% had at least high (or secondary) school literacy level.
      Quality-of-life measures suggested that most patients were physically, mentally
      and socially healthy. Higher education, income and functional capacity were
      associated with worse KUJ. CONCLUSION: The KUJ scale is internally consistent and
      clinicians can use it to identify the educational needs of patients with LPC
      before treatment selection. Overall, patients who were socioeconomically
      disadvantaged and those with physical ailments were better informed about the
      diagnosis, treatment options and prognosis of prostate cancer.

PMID- 20151970
TI  - A randomized, double-blind, placebo-controlled study of the efficacy and safety
      of bupropion for treating hypoactive sexual desire disorder in ovulating women.
AB  - OBJECTIVE: To compare the efficacy of sustained-release (SR) bupropion to placebo
      in treating hypoactive sexual desire disorder (HSDD) in ovulating women. PATIENTS
      AND METHODS: After a 1-week, placebo lead-in phase, 232 treatment-seeking women
      with regular menstrual cycles were randomly assigned to bupropion SR 150 mg/daily
      (116) or placebo (116) for 12 weeks under double-blind conditions. Efficacy was
      assessed with the Brief Index of Sexual Functioning for Women (BISF-W), the
      Personal Distress Scale (PDS), the global efficacy question (GEQ; 'Did the
      treatment you received during the 12-week improve meaningful your sexual
      desire?') and overall patient satisfaction question ('Are you satisfied with the
      efficacy of your treatment?'). RESULTS: The mean (sd) composite score on the BISF
      W, increased from 15.8 (2.6) and 15.5 (2.2) at baseline to 33.9 (4.2) and 16.9
      (2.6) in the bupropion and placebo groups, respectively (P= 0.001). The odds
      ratio (95% confidence interval) for response in the bupropion group relative to
      placebo was 3.2 (2.1-6.3). The thoughts/desire score more than doubled in
      patients treated with bupropion (P= 0.001). At the 12-week evaluation the
      reduction in the PDS scale was 29.4% in bupropion and 4.7% in the placebo group
      (P= 0.01). In response to the GEQ, of patients in the bupropion and placebo
      groups, 65.3%, and 4.3%, respectively, responded 'Definitely yes' (P= 0.001). Of
      patients in the bupropion and placebo groups, 71.8%, and 3.7%, respectively, were
      definitely satisfied with the efficacy of their treatment, (P= 0.001). After 12
      weeks of treatment, 82 women (78.1%) in the bupropion and five (4.9%) in the
      placebo group were willing to continue therapy (P= 0.001). CONCLUSIONS: The
      results from this study indicate that bupropion SR is an effective and well
      tolerated treatment for HSDD in ovulating women. Further controlled trials are
      warranted.

PMID- 20151971
TI  - A placebo-controlled exploratory study investigating the efficacy and safety of
      the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of men with
      storage lower urinary tract symptoms associated with a clinical diagnosis of
      overactive bladder.
AB  - OBJECTIVES: To evaluate the efficacy and safety of the phosphodiesterase type 5
      inhibitor, UK-369,003 modified release (MR), for the treatment of storage lower
      urinary tract symptoms (LUTS) in men with and without erectile dysfunction (ED).
      PATIENTS AND METHODS: This was a multicentre, double-blind, placebo-controlled,
      parallel-group study conducted across 50 centres in North and South America,
      Europe and Australia. In all, 310 men aged >= 18 years with a clinical diagnosis
      of overactive bladder (OAB; voiding frequency >= 8 times/24 h, urgency episode
      frequency once or more per 24 h and a mean voided volume of <300 mL) and maximum
      urinary flow rate of >5 mL/s in a voided volume of >150 mL were stratified into
      two groups (with or without ED) and randomized to one of five treatment groups
      (10, 25, 50 or 100 mg UK-369,003; or placebo once a day) for 12 weeks. The
      primary study endpoints were those derived from the bladder diary that recorded
      the number of voluntary urinary voids, volume of urine per void, leaks and
      urgency episodes over a 72-h period, before baseline and again at 2, 4 and 12
      weeks. Secondary efficacy measures included the International Prostate Symptom
      Score (total and storage and voiding subscores), International Index of Erectile
      Function-Erectile Function domain (IIEF-EF), questions 5 and 6 of the Quality of
      Erection Questionnaire (QEQ), the Overactive Bladder Questionnaire Short Form,
      the Patient Perception of Bladder Condition, the International Consultation on
      Incontinence Questionnaire-Male LUTS, and the patient-reported treatment impact
      questionnaire. RESULTS: Overall, there were no clinically relevant treatment
      differences in voiding frequency, mean voided volume, urgency episode frequency,
      or nocturia frequency for any dose of UK-369,003 MR compared with placebo. In the
      subset of patients with ED there were improvements in the IIEF-EF and QEQ scores
      in all UK-369,003 treatment groups compared with placebo. CONCLUSIONS: These data
      provide no evidence of efficacy for UK-369,003 in the treatment of storage LUTS
      in men (based on classic OAB eligibility criteria). However, although the
      endpoints on these classic OAB efficacy variables were negative, there is
      evidence to suggest a greater preference, satisfaction and willingness to use UK
      369,003 again for all treatment groups compared with placebo.

PMID- 20151972
TI  - Fesoterodine in patients with overactive bladder syndrome: can the severity of
      baseline urgency urinary incontinence predict dosing requirement?
AB  - OBJECTIVES: To determine whether baseline urgency urinary incontinence (UUI)
      episodes predict the need for increased doses of fesoterodine in patients with
      overactive bladder (OAB), as clinicians would benefit from data that help to
      predict which patients require higher doses of antimuscarinics to manage UUI
      episodes. PATIENTS AND METHODS: In this pooled analysis of data from two double
      blind, placebo-controlled trials, patients were randomized to placebo or
      fesoterodine 4 or 8 mg for 12 weeks and stratified into tertiles (>0-<2, 2-<4, or
      > or =4) according to the number of UUI episodes/24 h as recorded in 3-day
      bladder diaries at baseline. The change in mean UUI episodes/24 h from baseline
      to end of study was assessed using analysis of covariance. RESULTS: In a post hoc
      analysis of data from two clinical trials, there were significant reductions from
      baseline in UUI episodes for fesoterodine 4 and 8 mg vs placebo in patients (n)
      with >0-<2 (422), 2-<4 (424) and > or =4 (481) UUI episodes at baseline (all P <
      0.01). In patients with 2-<4 and > or =4 UUI episodes at baseline, fesoterodine 8
      mg gave significantly greater mean reductions (-1.92 and -4.17, respectively) vs
      fesoterodine 4 mg (-1.43 and -3.31) (P < 0.05). The most common adverse events
      were dry mouth (placebo, 8%; fesoterodine 4 mg, 19%; and 8 mg, 35%) and
      constipation (placebo, 2%; fesoterodine 4 mg, 5%; and 8 mg, 6%). CONCLUSION:
      Fesoterodine 4 and 8 mg significantly reduced UUI episodes vs placebo; this
      effect appeared to be greater with fesoterodine 8 mg in patients with > or =2 UUI
      episodes/24 h at baseline. Fesoterodine was well tolerated, although higher doses
      increased the incidence of adverse events. These findings might aid the clinical
      identification of patients with OAB who would most benefit from increasing the
      dose of fesoterodine from 4 to 8 mg.

PMID- 20151973
TI  - The management of pregnancy in paroxysmal nocturnal haemoglobinuria on long term
      eculizumab.
AB  - In Paroxysmal nocturnal haemoglobinuria (PNH), pregnancy is associated with
      increased maternal and foetal complications to such an extent that the condition
      has been considered relatively contra-indicated in PNH. Eculizumab has
      revolutionized the treatment of PNH. We evaluate its use in pregnancy to date. We
      report on seven patients exposed to eculizumab at different stages of pregnancy
      including the first two patients to receive the drug from conception to delivery.
      There was no evidence of complement blockade from cord blood samples taken at
      delivery. Eculizumab appears safe to use in this setting and is likely to prevent
      many of the complications usually observed.

PMID- 20151974
TI  - Prospects for the manufacture of red cells for transfusion.
AB  - Whilst red cell transfusion is a well established cellular therapy, the problems
      of insufficiency of supply, transfusion transmitted infections and the
      requirement for immunological matching persist. The possibility of generating
      large numbers of O Rh D negative red cells at Good Manufacturing Practice grade
      as a route to circumvent these issues is therefore an attractive proposition.
      Significant numbers of erythrocytes can be generated from somatic haematopoietic
      stem cells, but it seems unlikely that these can provide sufficient volumes for
      large scale manufacture. However, human embryonic stem cells (hESC) and,
      potentially, induced pluripotent stem cells (iPSC), may provide a route to this
      objective. Red cell transfusion is an attractive goal for pluripotent stem cell
      derived therapeutics because it is a well-characterised single cell suspension
      that lacks nucleated cells and has a low expression of human leucocyte antigen
      molecules, but many challenges remain in translating this cellular therapy to the
      clinic.

PMID- 20151975
TI  - The effect of rituximab on humoral and cell mediated immunity and infection in
      the treatment of autoimmune diseases.
AB  - Depletion of B lymphocytes using the anti-CD20 monoclonal antibody rituximab has
      wide-spread use in the treatment of patients with autoimmune disorders. As
      haematopoietic progenitor cells and only a fraction of differentiated plasma
      express CD20, the effect of rituximab on immune function appears to be minimal.
      However, hypogammagobulinaemia can occur with repeated doses and emerging data
      from large studies suggest a subtle increase in the risk of infection.
      Reactivation of latent JC virus, resulting in progressive multifocal
      leucoencephalopathy, and hepatitis B virus, resulting in hepatoxicity, have been
      documented in patients receiving rituximab; although confounding effects of
      concomitant immunosuppressive therapies and immune dysregulation due to the
      underlying disease make causal associations of infections problematic. This
      review discusses the efficacy of B cell depletion therapy in the treatment of
      autoimmune diseases, the effect of B cell depletion on infection and immunity
      including the role of the B cell in autoimmunity, and identifies areas of
      controversy.

PMID- 20151976
TI  - Clinical utility of routine MPL exon 10 analysis in the diagnosis of essential
      thrombocythaemia and primary myelofibrosis.
AB  - Approximately 50% of essential thrombocythaemia and primary myelo-fibrosis
      patients do not have a JAK2 V617F mutation. Up to 5% of these are reported to
      have a MPL exon 10 mutation but testing for MPL is not routine as there are
      multiple mutation types. The ability to routinely assess both JAK2 and MPL
      mutations would be beneficial in the differential diagnosis of unexplained
      thrombocytosis or myelofibrosis. We developed and applied a high resolution melt
      (HRM) assay, capable of detecting all known MPL mutations in a single analysis,
      for the detection of MPL exon 10 mutations. We assessed 175 ET and PMF patients,
      including 67 that were JAK2 V617F-negative by real time polymerase chain reaction
      (PCR). Overall, 19/175 (11%) patients had a MPL exon 10 mutation, of whom 16 were
      JAK2 V617F-negative (16/67; 24%). MPL mutation types were W515L (11), W515K (4),
      W515R (2) and W515A (1). One patient had both W515L and S505N MPL mutations and
      these were present in the same haemopoietic colonies. Real time PCR for JAK2
      V617F analysis and HRM for MPL exon 10 status identified one or more clonal
      marker in 71% of patients. This combined genetic approach increases the
      sensitivity of meeting the World Health Organization diagnostic criteria for
      these myeloproliferative neoplasms.

PMID- 20151977
TI  - Patients undergoing high dose chemotherapy for primary CNS lymphoma should
      receive prophylactic thiamine to prevent Wernike's encephalopathy.

PMID- 20151978
TI  - Influence of dietary vitamin K intake on subtherapeutic oral anticoagulant
      therapy.
AB  - It is unclear what advice should be given to patients using vitamin K antagonists
      with respect to dietary vitamin K intake. We performed a nested case-control
      study in patients attending a Dutch anticoagulation clinic, to determine the
      association between vitamin K intake and subtherapeutic International Normalized
      Ratio (INR) values and the interaction between usual and recent vitamin K intake.
      Compared to patients with a normal usual vitamin K intake, those with a high
      vitamin K intake had a decreased risk of a subtherapeutic INR [Hazard Ratio (HR)
      0.80, 95% confidence interval (CI): 0.56-1.16] and patients with a low vitamin K
      intake an increased risk (HR 1.33, 95% CI: 0.79-2.25). In patients with a low
      usual vitamin K intake, recent vitamin K intake was twice as high in cases as in
      controls (164 vs. 85 microg/d). Such a difference was not observed in patients
      with a normal or high usual vitamin K intake. Our results suggest that a high
      vitamin K intake reduces the risk of a low INR by lessening the influence of
      incidental consumption of vitamin K rich food on the INR. These findings support
      the recommendation for patients on vitamin K antagonists to eat a sufficient
      amount of vitamin-K containing foods.

PMID- 20151979
TI  - Targeting SYK kinase-dependent anti-apoptotic resistance pathway in B-lineage
      acute lymphoblastic leukaemia (ALL) cells with a potent SYK inhibitory
      pentapeptide mimic.
AB  - The present study found that the pentapeptide mimic C-61, targeting the substrate
      binding P-site of SYK tyrosine kinase acted as a potent inducer of apoptosis in
      chemotherapy-resistant SYK-expressing primary leukemic B-cell precursors taken
      directly from relapsed B-precursor leukaemia (BPL) patients (but not SYK
      deficient infant pro-B leukaemia cells), exhibited favourable pharmacokinetics in
      mice and non-human primates, and eradicated in vivo clonogenic leukaemia cells in
      severe combined immunodeficient mouse xenograft models of chemotherapy-resistant
      human BPL at dose levels non-toxic to mice and non-human primates. These in vitro
      and in vivo findings provide proof of principle for effective treatment of
      chemotherapy-resistant BPL by targeting SYK-dependent anti-apoptotic blast cell
      survival machinery with a SYK P-Site inhibitor. Further development of C-61 may
      provide the foundation for therapeutic innovation against chemotherapy-resistant
      BPL.

PMID- 20151980
TI  - The role of haematopoietic growth factors granulocyte colony-stimulating factor
      and granulocyte-macrophage colony-stimulating factor in the management of drug
      induced agranulocytosis.
AB  - Drug-induced agranulocytosis (neutrophil count <0.5 x 10(9)/l) is a rare
      haematological complication with an incidence of no more than 10 cases per
      million inhabitants per year in Europe. Over the past few years there has been a
      steady decline in mortality rate, (currently at <5%), which can be partly
      explained by earlier recognition and the improved clinical management of
      associated intercurrent infections that may lead to severe sepsis if left
      untreated. The true impact of the use of haematopoietic growth factors, such as
      granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony
      stimulating factor (GM-CSF), on the decreased mortality rate remains unknown.
      Yet, most studies show that these molecules, especially G-CSF, reduce the
      duration of agranulocytosis, antibiotic course and length of hospital stay. Their
      use is particularly recommended in patients with poor prognostic factors, such as
      a neutrophil count <0.1 x 10(9)/l, age over 65 years, severe infection or
      multiple co-morbidities. In all cases, the drug responsible for causing the
      agranulocytosis must be discontinued and remain permanently contraindicated. The
      appropriate Medicines Regulatory Agency must also be notified of the adverse
      event.

PMID- 20151981
TI  - Association between vitamin D and calcium intake and breast cancer risk according
      to menopausal status and receptor status in Japan.
AB  - Although several studies have investigated the possible association between
      elevated vitamin D and calcium intake and low breast cancer risk, findings have
      been inconsistent. We conducted a case-control study to clarify the association
      between vitamin D and calcium intake and breast cancer risk among pre- and post-
      menopausal women in Japan. We also investigated whether these effects were
      modified by tumor receptor status, specifically estrogen receptor (ER),
      progesterone receptor (PR), or human epidermal growth factor receptor-2 (HER2)
      status. We examined 1803 breast cancer patients and 3606 age- and menopausal
      status-matched noncancer controls. Among cases, 713 were assessed for ER, PR, and
      HER2 status. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated
      using conditional or unconditional logistic models adjusted for potential
      confounders. A significant inverse association was observed between vitamin D and
      calcium intake and breast cancer risk among all subjects, with top quartile ORs
      of 0.76 (95% CI, 0.63-0.90; trend P = 0.001) and 0.83 (95% CI, 0.69-0.99; trend P
      = 0.038), respectively. In analyses stratified by menopausal status, a
      significant association between risk and vitamin D was observed only among
      premenopausal women (trend P < 0.001), whereas that between risk and calcium
      intake was seen only among postmenopausal women (trend P = 0.022). Heterogeneity
      by menopausal status for these associations was statistically significant. This
      association was modified by tumor receptor status. These findings suggest that
      the protective effects of vitamin D and calcium intake against breast cancer risk
      may differ by menopausal status and receptor status.

PMID- 20151982
TI  - Up-regulation of pro-inflammatory genes as adaptation to hypoxia in MCF-7 cells
      and in human mammary invasive carcinoma microenvironment.
AB  - The role of tumor cells in synthesizing pro-inflammatory molecules is still
      controversial. Here we report that hypoxic treatment of the MCF-7 human mammary
      adenocarcinoma cell line induced activation of hypoxia-inducible factor 1alpha
      (HIF-1alpha) and nuclear factor-kappa B (NF-kappaB). Importantly, hypoxia
      regulated expression of alarmin receptors such as the receptor for advanced
      glycation end products (RAGE) and the purinoreceptor (P2X7R), and up-regulated
      inflammatory response (IR) genes such as the inducible enzymes nitric oxide
      synthase (NOS2), cycloxygenase (COX2), and the acute-phase protein pentraxin-3
      (PTX3). Hypoxia also stimulated chemokine (C-X-C motif) receptor 4 (CXCR4) mRNA
      synthesis. In fact, the CXCR4 ligand stromal-derived factor-1alpha (SDF-1alpha)
      increased invasion and migration of hypoxic MCF-7 cells. Inhibition of HIF-1alpha
      by chetomin and NF-kappaB by parthenolide reduced mRNA and protein expression of
      the studied molecules and prevented invasion of hypoxic MCF-7 cells. Moreover,
      solid invasive mammary tumor microenvironment was analyzed after laser-capture
      microdissection (LCMD) comparing tumor versus host normal tissue. Nuclear
      translocation of HIF-1alpha and NF-kappaB and up-regulation of IR, CXCR4,
      estrogen receptor alpha (ERalpha), and epithelial growth factor receptor (EGFR)
      was observed in tumor but not in host normal tissue in the absence of a local
      inflammatory leukocyte infiltrate. We conclude that under hypoxic conditions MCF
      7 cells acquire a pro-inflammatory phenotype, and that solid human mammary
      carcinoma evidenced a similar activation of HIF-1alpha, NF-kappaB, and IR genes
      in malignant tumor cells as compared to the normal host tissues. We suggest a
      role for IR activation in the malignant progression of transformed cells.

PMID- 20151983
TI  - 3-Methylcholanthrene-induced transforming growth factor-beta-producing
      carcinomas, but not sarcomas, are refractory to regulatory T cell-depletion
      therapy.
AB  - Regulatory T cells (Tregs) are major immunosuppressors in tumor-bearing hosts.
      Although Treg-depletion therapy has been shown to induce a complete cure in tumor
      bearing mice, this treatment is not always successful. Using 3-methylcholanthrene
      induced primary mouse tumors, we examined the distinct regulation of Treg
      mediated immunosuppression between carcinomas and sarcomas. We showed that the
      number of Tregs was greatly increased in squamous cell carcinoma (SCC)-bearing
      mice compared with sarcoma-bearing mice. This appeared to be because SCC produced
      higher levels of active transforming growth factor (TGF)-beta, which is essential
      for inducing Tregs, compared with sarcoma. Moreover, SCC, but not sarcomas, were
      refractory to Treg-depletion therapy by treatment with anti-CD25 mAb. The
      refractoriness of SCC against Treg-depletion therapy was due to the rapid
      recovery of Tregs in SCC-bearing mice compared with sarcoma-bearing mice.
      However, combination treatment of anti-TGF-beta mAb with anti-CD25 mAb caused a
      significant reduction in Treg recovery and induced a complete cure in SCC-bearing
      mice. Thus, we showed the refractoriness of mouse carcinoma against Treg
      depletion therapy using anti-CD25 mAb treatment. We also proposed a novel Treg
      blocking combination therapy using anti-CD25 mAb and anti-TGF-beta mAb to induce
      a complete cure of tumor-bearing hosts.

PMID- 20151984
TI  - Roads, interrupted dispersal, and genetic diversity in timber rattlesnakes.
AB  - Anthropogenic habitat modification often creates barriers to animal movement,
      transforming formerly contiguous habitat into a patchwork of habitat islands with
      low connectivity. Roadways are a feature of most landscapes that can act as
      barriers or filters to migration among local populations. Even small and recently
      constructed roads can have a significant impact on population genetic structure
      of some species, but not others. We developed a research approach that combines
      fine-scale molecular genetics with behavioral and ecological data to understand
      the impacts of roads on population structure and connectivity. We used
      microsatellite markers to characterize genetic variation within and among
      populations of timber rattlesnakes (Crotalus horridus) occupying communal
      hibernacula (dens) in regions bisected by roadways. We examined the impact of
      roads on seasonal migration, genetic diversity, and gene flow among populations.
      Snakes in hibernacula isolated by roads had significantly lower genetic diversity
      and higher genetic differentiation than snakes in hibernacula in contiguous
      habitat. Genetic-assignment analyses revealed that interruption to seasonal
      migration was the mechanism underlying these patterns. Our results underscore the
      sizeable impact of roads on this species, despite their relatively recent
      construction at our study sites (7 to 10 generations of rattlesnakes), the
      utility of population genetics for studies of road ecology, and the need for
      mitigating effects of roads.

PMID- 20151985
TI  - Effects of habitat fragmentation on effective dispersal of Florida scrub-jays.
AB  - Studies comparing dispersal in fragmented versus unfragmented landscapes show
      that habitat fragmentation alters the dispersal behavior of many species. We used
      two complementary approaches to explore Florida Scrub-Jay (Aphelocoma
      coerulescens) dispersal in relation to landscape fragmentation. First, we
      compared dispersal distances of color-marked individuals in intensively monitored
      continuous and fragmented landscapes. Second, we estimated effective dispersal
      relative to the degree of fragmentation (as inferred from two landscape indexes:
      proportion of study site covered with Florida Scrub-Jay habitat and mean distance
      to nearest habitat patch within each study site) by comparing genetic isolation
      by-distance regressions among 13 study sites having a range of landscape
      structures. Among color-banded individuals, dispersal distances were greater in
      fragmented versus continuous landscapes, a result consistent with other studies.
      Nevertheless, genetic analyses revealed that effective dispersal decreases as the
      proportion of habitat in the landscape decreases. These results suggest that
      although individual Florida Scrub-Jays may disperse farther as fragmentation
      increases, those that do so are less successful as breeders than those that
      disperse short distances. Our study highlights the importance of combining
      observational data with genetic inferences when evaluating the complex biological
      and life-history implications of dispersal.

PMID- 20151986
TI  - From adaptive management to adjustive management: a pragmatic account of
      biodiversity values.
AB  - The conservation of biodiversity poses an exceptionally difficult problem in that
      it needs to be effective in a context of double uncertainty: scientific (i.e.,
      how to conserve biodiversity) and normative (i.e., which biodiversity to conserve
      and why). Although adaptive management offers a promising approach to overcome
      scientific uncertainty, normative uncertainty is seldom tackled by conservation
      science. We expanded on the approach proposed by adaptive-management theorists by
      devising an integrative and iterative approach to conservation that encompasses
      both types of uncertainty. Inspired by environmental pragmatism, we suggest that
      moral values at stake in biodiversity conservation are plastic and that a
      plurality of individual normative positions can coexist and evolve. Moral values
      should thus be explored through an experimental process as additional parameters
      to be incorporated in the traditional adaptive-management approach. As such,
      moral values should also be monitored by environmental ethicists working side by
      side with scientists and managers on conservation projects. Acknowledging the
      diversity of moral values and integrating them in a process of collective
      deliberation will help overcome the normative uncertainty. We used Dewey's
      distinction between adaptation and adjustment to offer a new paradigm built
      around what we call adjustive management, which reflects both the uncertainty and
      the likely evolution of the moral values humans attribute to biodiversity. We
      illustrate how this paradigm relates to practical conservation decisions by
      exploring the case of the Sacred Ibis (Threskiornis aethiopicus), an alien
      species in France that is the target of an eradication plan undertaken with
      little regard for moral issues. We propose that a more satisfying result of
      efforts to control Sacred Ibis could have been reached by rerouting the
      traditional feedback loop of adaptive management to include a normative inquiry.
      This adjustive management approach now needs to be tested in real-case
      conservation programs.

PMID- 20151987
TI  - Key features and context-dependence of fishery-induced trophic cascades.
AB  - Trophic cascades triggered by fishing have profound implications for marine
      ecosystems and the socioeconomic systems that depend on them. With the number of
      reported cases quickly growing, key features and commonalities have emerged.
      Fishery-induced trophic cascades often display differential response times and
      nonlinear trajectories among trophic levels and can be accompanied by shifts in
      alternative states. Furthermore, their magnitude appears to be context dependent,
      varying as a function of species diversity, regional oceanography, local physical
      disturbance, habitat complexity, and the nature of the fishery itself. To
      conserve and manage exploited marine ecosystems, there is a pressing need for an
      improved understanding of the conditions that promote or inhibit the cascading
      consequences of fishing. Future research should investigate how the trophic
      effects of fishing interact with other human disturbances, identify strongly
      interacting species and ecosystem features that confer resilience to
      exploitation, determine ranges of predator depletion that elicit trophic
      cascades, pinpoint antecedents that signal ecosystem state shifts, and quantify
      variation in trophic rates across oceanographic conditions. This information will
      advance predictive models designed to forecast the trophic effects of fishing and
      will allow managers to better anticipate and avoid fishery-induced trophic
      cascades.

PMID- 20151988
TI  - Geography and recovery under the U.S. Endangered Species Act.
AB  - The U.S. Endangered Species Act (ESA) defines an endangered species as one "at
      risk of extinction throughout all or a significant portion of its range." The
      prevailing interpretation of this phrase, which focuses exclusively on the
      overall viability of listed species without regard to their geographic
      distribution, has led to development of listing and recovery criteria with
      fundamental conceptual, legal, and practical shortcomings. The ESA's concept of
      endangerment is broader than the biological concept of extinction risk in that
      the "esthetic, ecological, educational, historical, recreational, and scientific"
      values provided by species are not necessarily furthered by a species mere
      existence, but rather by a species presence across much of its former range. The
      concept of "significant portion of range" thus implies an additional geographic
      component to recovery that may enhance viability, but also offers independent
      benefits that Congress intended the act to achieve. Although the ESA differs from
      other major endangered-species protection laws because it acknowledges the
      distinct contribution of geography to recovery, it resembles the "representation,
      resiliency, and redundancy" conservation-planning framework commonly referenced
      in recovery plans. To address representation, listing and recovery standards
      should consider not only what proportion of its former range a species inhabits,
      but the types of habitats a species occupies and the ecological role it plays
      there. Recovery planning for formerly widely distributed species (e.g., the gray
      wolf [Canis lupus]) exemplifies how the geographic component implicit in the
      ESA's definition of endangerment should be considered in determining recovery
      goals through identification of ecologically significant types or niche variation
      within the extent of listed species, subspecies, or "distinct population
      segments." By linking listing and recovery standards to niche and ecosystem
      concepts, the concept of ecologically significant type offers a scientific
      framework that promotes more coherent dialogue concerning the societal decisions
      surrounding recovery of endangered species.

PMID- 20151989
TI  - Effects of land-use change on community composition of tropical amphibians and
      reptiles in Sulawesi, Indonesia.
AB  - Little is known about the effects of anthropogenic land-use change on the
      amphibians and reptiles of the biodiverse tropical forests of Southeast Asia. We
      studied a land-use modification gradient stretching from primary forest,
      secondary forest, natural-shade cacao agroforest, planted-shade cacao agroforest
      to open areas in central Sulawesi, Indonesia. We determined species richness,
      abundance, turnover, and community composition in all habitat types and related
      these to environmental correlates, such as canopy heterogeneity and thickness of
      leaf litter. Amphibian species richness decreased systematically along the land
      use modification gradient, but reptile richness and abundance peaked in natural
      shade cacao agroforests. Species richness and abundance patterns across the
      disturbance gradient were best explained by canopy cover and leaf-litter
      thickness in amphibians and by canopy heterogeneity and cover in reptiles.
      Amphibians were more severely affected by forest disturbance in Sulawesi than
      reptiles. Heterogeneous canopy cover and thick leaf litter should be maintained
      in cacao plantations to facilitate the conservation value for both groups. For
      long-term and sustainable use of plantations, pruned shade trees should be
      permanently kept to allow rejuvenation of cacao and, thus, to prevent repeated
      forest encroachment.

PMID- 20151990
TI  - Quantitative assessment of a Tanzanian integrated conservation and development
      project involving butterfly farming.
AB  - Scientific understanding of the role of development in conservation has been
      hindered by the quality of evaluations of integrated conservation and development
      projects. We used a quasi-experimental design to quantitatively assess a
      conservation and development project involving commercial butterfly farming in
      the East Usambara Mountains of Tanzania. Using a survey of conservation
      attitudes, beliefs, knowledge, and behavior, we compared 150 butterfly farmers
      with a control group of 170 fellow community members. Due to the nonrandom
      assignment of individuals to the two groups, we used propensity-score matching
      and weighting in our analyses to control for observed bias. Eighty percent of the
      farmers believed butterfly farming would be impossible if local forests were
      cleared, and butterfly farmers reported significantly more participation in
      forest conservation behaviors and were more likely to believe that conservation
      behaviors were effective. The two groups did not differ in terms of their general
      conservation attitudes, attitudes toward conservation officials, or knowledge of
      conservation-friendly building techniques. The relationship between butterfly
      farming and conservation behavior was mediated by dependency on butterfly farming
      income. Assuming unobserved bias played a limited role, our findings suggest that
      participation in butterfly farming increased participation in conservation
      behaviors among project participants because farmers perceive a link between
      earnings from butterfly farming and forest conservation.

PMID- 20151991
TI  - Multiple sequences and factors are involved in stability/degradation of Awnt-1,
      Awnt-5A and Awnt-5B mRNAs during axolotl development.
AB  - Following fertilization in amphibian, early cleavage stages are maternally
      controlled at a post-transcriptional level before initiation of zygotic
      transcriptions at the mid blastula transition (MBT). We document the expression
      levels of the axolotl Awnt-1, Awnt-5A and Awnt-5B genes as well as the
      adenylation states of their corresponding mRNAs from the end of oogenesis until
      the tailbud stages. Awnt-1/-5A RNAs are stable until MBT then degraded before
      gastrulation. Awnt-5B RNAs are degraded at fertilization and zygotically
      expressed after MBT with high level expression from gastrulation. Estimation of
      the poly(A) tail lengths reveals no direct link between deadenylation and
      degradation periods for each Awnt transcript. To investigate the molecular
      mechanisms involved in Awnt-1/-5A/-5B RNAs stability, synthetic full-length or 3'
      untranslated region (UTR) Awnt RNAs progressively deleted from their 3' end were
      microinjected in axolotl oocytes, unfertilized and fertilized eggs. We identified
      degrading and stabilizing sequences in the 3'UTR whose activities depend on the
      cellular context and are also modulated by the 5'UTR and coding sequence within
      each RNA. Using axolotl nuclear extracts from stage VI oocytes, we further
      produced evidence of destabilizing factors targeting the Awnt-5B RNAs.
      Altogether, these results show that oocyte maturation and late cleavages
      following MBT are two important periods when axolotl Wnt RNAs are highly
      regulated.

PMID- 20151992
TI  - Perturbation of Notch/Suppressor of Hairless pathway disturbs migration of
      primordial germ cells in Xenopus embryo.
AB  - Primordial germ cells (PGCs) in Xenopus embryo are specified in the endodermal
      cell mass and migrate dorsally toward the future gonads. The role of the signal
      mediated by Notch and Suppressor of Hairless [Su(H)] was analyzed on the
      migrating PGCs at the tailbud stage. X-Notch-1 and X-Delta-1 are expressed in the
      migrating PGCs and surrounding endodermal cells, whereas X-Delta-2 and X-Serrate
      1 are expressed preferentially in the PGCs. Suppression and constitutive
      activation of the Notch/Su(H) signaling in the whole endoderm region or
      selectively in the PGCs resulted in an increase in ectopic PGCs located in
      lateral or ventral regions. Knocking down of the Notch ligands by morpholino
      oligonucleotides revealed that X-Delta-2 was indispensable for the correct PGC
      migration. The ectopic PGCs seemed to have lost their motility in the Notch/Su(H)
      signal-manipulated embryos. Our results suggest that a cell-to-cell interaction
      via the Notch/Su(H) pathway has a significant role in the PGC migration by
      regulating cell motility.

PMID- 20151993
TI  - Abstracts of Diabetes UK Annual Professional Conference. Liverpool, United
      Kingdom. March 3-5, 2010.

PMID- 20151994
TI  - Oral insulin - a review of current status.
AB  - Oral insulin is one of the most exciting areas of development in the treatment of
      diabetes because of its potential benefit in patient convenience, rapid
      insulinization of liver, adequate insulin delivery avoiding peripheral
      hyperinsulinaemia while potentially avoiding adverse effects of weight gain and
      hypoglycaemia. Growing evidence that earlier initiation of intensive insulin
      therapy produces sustained tight glycaemic control resulting in substantial delay
      in complications makes an effective oral insulin product even more vital for the
      management of patients with diabetes. Despite knowledge of this unmet medical
      need, oral delivery of insulin has been unsuccessful because of several barriers.
      For several decades, researchers have tried to develop oral insulin using various
      technologies without much clinical or commercial success. This review summarizes
      the development status of oral insulins which are publicly reported to be
      undergoing clinical studies. Currently, two oral insulin products are in an
      advanced stage of clinical development and first data from long-term therapy are
      expected to be available in the second half of 2010.

PMID- 20151995
TI  - Benefits of moderate weight loss in patients with type 2 diabetes.
AB  - Weight loss is a primary goal of therapy in overweight patients with type 2
      diabetes. This review examines whether positive patient outcomes are observed
      even after relatively small amounts of weight loss, that is, weight loss being
      more easily attainable in practice. Clinical studies demonstrate that therapeutic
      benefit rises with increasing weight loss, but that losses as low as 0.45-4 kg (1
      9 lb) have positive effects on metabolic control, cardiovascular risk factors and
      mortality rates. Even the intention to lose weight, without significant success,
      can improve outcomes in patients with diabetes, presumably because of the healthy
      behaviours associated with the attempt. The current data support a continued
      focus on weight loss, including moderate weight loss, as a key component of good
      care for overweight patients with type 2 diabetes.

PMID- 20151996
TI  - A low carbohydrate Mediterranean diet improves cardiovascular risk factors and
      diabetes control among overweight patients with type 2 diabetes mellitus: a 1
      year prospective randomized intervention study.
AB  - BACKGROUND: The appropriate dietary intervention for overweight persons with type
      2 diabetes mellitus (DM2) is unclear. Trials comparing the effectiveness of diets
      are frequently limited by short follow-up times and high dropout rates. AIM: The
      effects of a low carbohydrate Mediterranean (LCM), a traditional Mediterranean
      (TM), and the 2003 American Diabetic Association (ADA) diet were compared, on
      health parameters during a 12-month period. METHODS: In this 12-month trial, 259
      overweight diabetic patients (mean age 55 years, mean body mass index 31.4
      kg/m(2)) were randomly assigned to one of the three diets. The primary end-points
      were reduction of fasting plasma glucose, HbA1c and triglyceride (TG) levels.
      RESULTS: 194 patients out of 259 (74.9%) completed follow-up. After 12 months,
      the mean weight loss for all patients was 8.3 kg: 7.7 kg for ADA, 7.4 kg for TM
      and 10.1 kg for LCM diets. The reduction in HbA1c was significantly greater in
      the LCM diet than in the ADA diet (-2.0 and -1.6%, respectively, p < 0.022). HDL
      cholesterol increased (0.1 mmol/l +/- 0.02) only on the LCM (p < 0.002). The
      reduction in serum TG was greater in the LCM (-1.3 mmol/l) and TM (-1.5 mmol/l)
      than in the ADA (-0.7 mmol/l), p = 0.001. CONCLUSIONS: An intensive 12-month
      dietary intervention in a community-based setting was effective in improving most
      modifiable cardiovascular risk factors in all the dietary groups. Only the LCM
      improved HDL levels and was superior to both the ADA and TM in improving
      glycaemic control.

PMID- 20151997
TI  - Ezetimibe added to atorvastatin compared with doubling the atorvastatin dose in
      patients at high risk for coronary heart disease with diabetes mellitus,
      metabolic syndrome or neither.
AB  - AIM: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are both
      associated with increased risk for atherosclerotic coronary heart disease (CHD).
      Thus, it is useful to know the relative efficacy of lipid-altering drugs in these
      patient populations. METHODS: A double-blind, parallel group trial of adult
      patients with hypercholesterolaemia at high-CHD risk receiving atorvastatin 40
      mg/day compared atorvastatin 40 mg plus ezetimibe 10 mg (ezetimibe) vs. doubling
      atorvastatin to 80 mg. This post hoc analysis reports lipid efficacy results in
      patients grouped by diagnosis of T2DM, MetS without T2DM or neither. Per cent
      change from baseline at week 6 was assessed for LDL-C, total cholesterol, HDL-C ,
      non-HDL-C , Apo A-I, Apo B and triglycerides. Safety was monitored through
      clinical and laboratory adverse events (AEs). RESULTS: Compared with doubling
      atorvastatin, atorvastatin plus ezetimibe resulted in greater reductions in LDL
      C, triglycerides, Apo B, non-HDL-C, total cholesterol and lipid ratios in the
      T2DM, MetS and neither groups. Treatment effects were of similar magnitude across
      patient groups with both treatments, except triglycerides, which were slightly
      greater in the T2DM and MetS groups vs. neither group. Changes in HDL-C , Apo A-I
      and high sensitivity C-reactive protein (hs-CRP) were comparable for both
      treatments in all three groups. Safety and tolerability profiles were generally
      similar between treatments and across patient groups, as were the incidence of
      liver and muscle AEs. CONCLUSIONS: Compared with doubling atorvastatin to 80 mg,
      addition of ezetimibe to atorvastatin 40 mg produced greater improvements in
      multiple lipid parameters in high-CHD risk patients with T2DM, MetS or neither,
      consistent with the significantly greater changes observed in the full study
      cohort (clinical trial # NCT00276484).

PMID- 20151998
TI  - Open-label study to assess the safety and pharmacodynamics of five oral insulin
      formulations in healthy subjects.
AB  - AIM: Orally delivered insulin is predicted to bear therapeutic advantages in
      diabetes management when compared to injectable insulin, because of its ability
      to mimic the natural route of endogenous insulin secreted by the pancreas into
      the portal vein and directly to the liver. Oramed Pharmaceuticals is developing
      an oral insulin product which consists of unmodified recombinant human insulin
      combined with adjuvants that protect it from enzymatic degradation in the
      gastrointestinal tract and promote its absorption from the gut. The aim was to
      determine the optimal adjuvants to insulin ratio which can provide for the best
      pharmacodynamic profile, while maintaining the safety of the product. METHODS:
      Eight healthy, male volunteers participated in this open-label study which
      included five independent visits. During each visit, subjects were administered
      one of the five encapsulated oral insulin formulations which contained equal
      amounts of insulin but varying proportions of adjuvants. Parameters measured
      included safety, C(max) and T(max) for insulin and C(min), T(min) and area under
      the curve (AUC) for glucose and c-peptide. Comparisons were made between
      formulations and between post-treatment time periods within each visit. RESULTS:
      All five oral insulin formulations were well tolerated and no serious adverse
      events were reported. All formulations resulted in a significant response in the
      response period (60-300 min) in comparison to baseline (0-60 min); this was
      captured both in the c-peptide response and the glucose response (all five
      formulations p < 0.05). However, none of the formulations turned out
      significantly different in response over the other. Formulation 5 showed the most
      profound reduction in c-peptide when AUC(0-60) (baseline) was compared to AUC(60
      300) (p < 0.007). CONCLUSIONS: All five oral insulin formulations resulted in
      glucose and c-peptide reductions, where formulation 5 demonstrated the most
      pronounced effect on c-peptide concentration reduction. This formulation was
      deemed the lead formulation to be advanced to future clinical studies. This study
      also reinforces the notion that oral insulin can maintain its biological activity
      after delivery, suggesting a potential role for this product in management of
      diabetes.

PMID- 20151999
TI  - Combination treatment with alogliptin and voglibose increases active GLP-1
      circulation, prevents the development of diabetes and preserves pancreatic beta
      cells in prediabetic db/db mice.
AB  - AIM: Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and voglibose, an
      alpha-glucosidase inhibitor, have different but complementary mechanisms of
      action on glucagon-like peptide-1 (GLP-1) regulation and glucose-lowering
      effects. The present study evaluated the chronic effects of combination treatment
      with alogliptin and voglibose in prediabetic db/db mice. METHODS: Alogliptin
      (0.03%) and voglibose (0.001%) alone or in combination were administered in the
      diet to prediabetic db/db mice. RESULTS: After 3 weeks, voglibose treatment
      increased GLP-1 secretion (voglibose alone, 1.6-fold; alogliptin plus voglibose,
      1.5-fold), while it decreased plasma glucose-dependent insulinotropic polypeptide
      (GIP) (voglibose alone, -30%; alogliptin plus voglibose, -29%). Alogliptin,
      voglibose and combination treatment decreased plasma DPP-4 activity by 72, 15 and
      additively by 80%, respectively, and increased plasma active GLP-1 levels by 4.5
      , 1.8- and synergistically by 9.1-fold respectively. Combination treatment
      increased plasma insulin by 3.6-fold (alogliptin alone, 1.3-fold; voglibose
      alone, 1.8-fold), decreased plasma glucagon by 30% (alogliptin alone, 11%;
      voglibose alone, 8%), and prevented the development of diabetes, much more
      effectively than either agent alone. After 4 weeks, alogliptin, voglibose and
      combination treatment increased pancreatic insulin content by 1.6-, 3.4- and
      synergistically by 8.5-fold respectively. Furthermore, combination treatment
      resulted in an increased expression of insulin, pancreatic and duodenal homeobox
      1 (PDX1) and glucose transporter 2 (GLUT2), and maintenance of normal beta/alpha
      cell distribution in the pancreatic islet. CONCLUSIONS: Chronic treatment with
      alogliptin in combination with voglibose concurrently increased active GLP-1
      circulation, increased insulin secretion, decreased glucagon secretion, prevented
      the onset of the disease, and preserved pancreatic beta-cells and islet structure
      in prediabetic db/db mice.

PMID- 20152000
TI  - Modulation of nutrient sensing nuclear hormone receptors promotes weight loss
      through appetite suppression in mice.
AB  - AIM: Peroxisome proliferator activated receptors (PPARs) are nuclear receptors
      involved in glucose and lipid metabolism. Three isoforms of PPARs have been
      identified with different tissue distribution and biological functions. Although
      the pharmacology of each receptor is well studied, the physiological effect of
      simultaneous activation of PPARalpha, gamma and delta is only starting to emerge.
      We sought to determine the biological effects of a novel PPAR pan activator and
      elucidate the physiological mechanisms involved. METHODS: Ob/ob, diet-induced
      obese (DIO) or PPARalpha knockout mice were administered a novel agonist that
      activates all PPARs to various degrees to determine the effect on body weight,
      body composition, food intake and energy expenditure. In addition, serum
      parameters including glucose, insulin, triglycerides and ketone bodies as well as
      tissue acylcarnitine were evaluated. The effect of the novel agonist on liver and
      skeletal muscle histopathology was also studied. RESULTS: We report that
      simultaneous activation of all PPARs resulted in substantial weight loss in ob/ob
      and DIO mice. Consistent with known PPAR pharmacology, we observed that agonist
      treatment increased lipid oxidation, although appetite suppression was mainly
      responsible for the weight loss. Agonist-induced weight loss was completely
      absent in PPARalpha knockout mice suggesting that PPARalpha pharmacology was the
      major contributor to weight regulation in mice. CONCLUSIONS: Our work provides
      evidence that simultaneous activation of PPARalpha, gamma and delta decreases
      body weight by regulating appetite. These effects of the pan agonist were
      completely absent in PPARalpha knockout mice, suggesting that PPARalpha
      pharmacology was the major contributor to weight loss.

PMID- 20152003
TI  - Chest pain research; no more comparing apples with oranges.

PMID- 20152004
TI  - Does the standard intravenous solution of fentanyl (50 microg/mL) administered
      intranasally have analgesic efficacy?
AB  - BACKGROUND: Intranasal (IN) fentanyl provides rapid and powerful non-parenteral
      analgesia in the ED. A concentrated solution of fentanyl (300 microg/mL) has been
      used in prior trials, yet many ED use the standard solution at a concentration of
      50 microg/mL, which is widely available and of low cost. We set out to determine
      if this lower concentration of fentanyl is also efficacious. METHODS: Prospective
      audit in children aged 5-18 years presenting with upper limb injuries. Patients
      received IN fentanyl (50 microg/mL) at 1.5 microg/kg. Patient assessed pain
      scores were collected 5, 10, 20, 30 and 60 min following IN fentanyl
      administration using a visual analogue scale or Bieri Faces-Revised scale.
      Parental scores were used if patients were unable to provide a score. RESULTS: Of
      the 59 eligible patients, 36 were enrolled; median age was 6.8 years (range 5-15
      years), and 89% (32/36) ultimately required fracture reduction. Median first dose
      of IN fentanyl was 1.4 microg/kg. Median pain scores dropped from 7
      (interquartile range 5-10) pre-fentanyl to 5 (interquartile range 4-8) at 5 min
      and 2 (interquartile range 1-4) at 30 and 60 min. A total of 21 (58%) children
      did not require further analgesia in the ED. There were no adverse events.
      CONCLUSIONS: Standard i.v. concentration IN fentanyl (50 microg/mL) appears to
      have analgesic efficacy in children with upper limb injuries.

PMID- 20152005
TI  - Best Guess method: a further external validation study and comparison with other
      methods.
AB  - OBJECTIVE: Validation of the 'Best Guess' weight estimation method on a
      geographically divergent external sample of children, plus comparison with APLS
      and Broselow weight estimation methods. METHODS: Prospective cross-sectional
      analytical study at Princess Margaret Hospital Emergency Department. A
      convenience sample of children aged 0-14 years recruited from May to June 2008.
      Age, sex, ethnicity, height and actual weight obtained. Agreement between the
      methods is reported as a comparative mean and distribution of the percentage
      error, plus the proportion of instances where the error exceeded 20% of the
      measured weight. RESULTS: A total of 1235 children were included. The 'Best
      Guess' method was the most accurate, particularly in children aged 1-4 years
      (mean percentage error +1.69%). In other age groups it overestimated weight, with
      mean percentage errors ranging from 3.41% to 6.25%. Across all age groups the
      Broselow method was most precise, with tendency to underestimate weight across
      age groups with mean percentage errors ranging from -5.28% to -7.24%. The APLS
      method was least accurate and precise, with mean percentage errors ranging from 
      12.61% to -17.36%. Net weight underestimation errors exceeding 20% were
      associated with increased mean body mass index. CONCLUSION: The Best Guess weight
      estimation method is accurate, especially in children aged 1-4 years. It
      moderately overestimates weight in other ages. The Broselow method was more
      precise, whereas the APLS method was the least accurate and precise of all. The
      ease of use of the Broselow method argues for greater use in the ED and
      prehospital setting.

PMID- 20152006
TI  - Emergency medicine in the Netherlands.
AB  - The Dutch health-care system provides high-quality inpatient care, but emergency
      care apart from trauma is poorly developed. A model for emergency medicine based
      on Anglo-American and Australasian principles was introduced in 2000, and a
      national integrated training curriculum was introduced in 2007. There exist many
      impediments and opposition to the acceptance of emergency medicine as a defined
      discipline. Despite this emergency medicine became a recognized specialty this
      year (2009). The present paper gives an overview of the Dutch health-care system
      and the history, current status, training and future development of emergency
      medicine in the Netherlands.

PMID- 20152007
TI  - Liquefied petroleum gas cold burn sustained while refueling a car.
AB  - There have been few cases of cold burn related to the exposure of liquid
      petroleum gas (LPG). We present the case of a young woman exposed to LPG while
      refueling her car who sustained partial thickness burns to the dorsum of her
      hand. Contact with LPG leaking from a pressurized system causes tissue damage
      because of cold injury. Immediate management of LPG is extrapolated from the
      management of frostbite. The increasing use of LPG mandates an awareness of
      prevention strategies and management principles in the setting of adverse events.

PMID- 20152008
TI  - Extracorporeal membrane oxygenation as a resuscitation measure in the emergency
      department.
AB  - A 53-year-old man presented to the ED with refractory ventricular fibrillation
      secondary to an occluded proximal left anterior descending coronary artery. We
      report the first case of extracorporeal membrane oxygenation instituted in our
      ED. It is one of the few reports in the literature of extracorporeal membrane
      oxygenation being utilized in the ED as a resuscitation measure.

PMID- 20152009
TI  - Peripheral neuropathy following nitrous oxide abuse.
AB  - Undifferentiated neurological presentations are not uncommon to the ED. Vitamin B
      (12) deficiency can lead to progressive demyelination and axonal lesions on the
      peripheral nerves and cervicothoracic spinal cord causing a peripheral
      neuropathy. Nitrous oxide is a common adjuvant to anaesthesia in the ED but it
      not often thought of as a drug of abuse. A case is reported of prolonged and
      intensive nitrous oxide abuse that resulted in the development of a peripheral
      neuropathy.

PMID- 20152010
TI  - Limitations to diagnostic coding accuracy in emergency departments: implications
      for research and audits of care.

PMID- 20152013
TI  - Structural diversity and evolution of the N-terminal isoform-specific region of
      ecdysone receptor-A and -B1 isoforms in insects.
AB  - BACKGROUND: The ecdysone receptor (EcR) regulates various cellular responses to
      ecdysteroids during insect development. Insects have multiple EcR isoforms with
      different N-terminal A/B domains that contain the isoform-specific activation
      function (AF)-1 region. Although distinct physiologic functions of the EcR
      isoforms have been characterized in higher holometabolous insects, they remain
      unclear in basal direct-developing insects, in which only A isoform has been
      identified. To examine the structural basis of the EcR isoform-specific AF-1
      regions, we performed a comprehensive structural comparison of the isoform
      specific region of the EcR-A and -B1 isoforms in insects. RESULTS: The EcR
      isoforms were newly identified in 51 species of insects and non-insect
      arthropods, including direct-developing ametabolous and hemimetabolous insects.
      The comprehensive structural comparison revealed that the isoform-specific region
      of each EcR isoform contained evolutionally conserved microdomain structures and
      insect subgroup-specific structural modifications. The A isoform-specific region
      generally contained four conserved microdomains, including the SUMOylation motif
      and the nuclear localization signal, whereas the B1 isoform-specific region
      contained three conserved microdomains, including an acidic activator domain-like
      motif. In addition, the EcR-B1 isoform of holometabolous insects had a novel
      microdomain at the N-terminal end. CONCLUSIONS: Given that the nuclear receptor
      AF-1 is involved in cofactor recruitment and transcriptional regulation, the
      microdomain structures identified in the isoform-specific A/B domains might
      function as signature motifs and/or as targets for cofactor proteins that play
      essential roles in the EcR isoform-specific AF-1 regions. Moreover, the novel
      microdomain in the isoform-specific region of the holometabolous insect EcR-B1
      isoform suggests that the holometabolous insect EcR-B1 acquired additional
      transcriptional regulation mechanisms.

PMID- 20152015
TI  - General practitioners and tutors' experiences with peer group academic detailing:
      a qualitative study.
AB  - BACKGROUND: The Prescription Peer Academic Detailing (Rx-PAD) project is an
      educational intervention study aiming at improving GPs' competence in
      pharmacotherapy. GPs in CME peer groups were randomised to receive a tailored
      intervention, either to support a safer prescription practice for elderly
      patients or to improve prescribing of antibiotics to patients with respiratory
      tract infections. The project was based on the principles of peer group academic
      detailing, incorporating individual feedback on GPs' prescription patterns. We
      did a study to explore GPs and tutors' experiences with peer group academic
      detailing, and to explore GPs' reasons for deviating from recommended prescribing
      practice. METHODS: Data was collected through nine focus group interviews with a
      total of 39 GPs and 20 tutors. Transcripts from the interviews were analyzed by
      two researchers according to a procedure for thematic content analysis. RESULTS:
      A shared understanding of the complex decision-making involved in prescribing in
      general practice was reported by both GPs and tutors as essential for an open
      discussion in the CME groups. Tutors experienced that CME groups differed
      regarding structure and atmosphere, and in some groups it was a challenge to run
      the scheme as planned. Individual feedback motivated GPs to reflect on and to
      improve their prescribing practice, though feedback reports could cause distress
      if the prescribing practice was unfavourable. Explanations for inappropriate
      prescriptions were lack of knowledge, factors associated with patients, the GP's
      background, the practice, and other health professionals or health care
      facilities. CONCLUSIONS: GPs and tutors experienced peer group academic detailing
      as a suitable method to discuss and learn more about pharmacotherapy. An
      important outcome for GPs was being more reflective about their prescriptions.
      Disclosure of inappropriate prescribing can cause distress in some doctors, and
      tutors must be prepared to recognise and manage such reactions.

PMID- 20152014
TI  - Differential expression level of cytokeratin 8 in cells of the bovine nucleus
      pulposus complicates the search for specific intervertebral disc cell markers.
AB  - INTRODUCTION: Development of cell therapies for repairing the intervertebral disc
      is limited by the lack of a source of healthy human disc cells. Stem cells,
      particularly mesenchymal stem cells, are seen as a potential source but
      differentiation strategies are limited by the lack of specific markers that can
      distinguish disc cells from articular chondrocytes. METHODS: We searched for
      markers using the differential in-gel electrophoresis proteomic technology to
      compare proteins of bovine nucleus pulposus cells, phenotypically similar to
      mature human nucleus cells, with those of bovine articular chondrocytes. In the
      cohort of the differentially expressed proteins identified by mass spectrometry,
      cytokeratin 8 (CK8) was further validated by immunostaining of freshly isolated
      cells and frozen tissue sections using monoclonal antibodies. RESULTS: We
      identified a set of 14 differentially expressed proteins. Immunohistochemistry
      showed that only a subset of cells (approximately 10%) was positive for one of
      these proteins, CK8, an intermediate filament protein present in epithelial but
      not mesenchymal cells. In tissue sections, CK8-positive cells were seen in all
      discs examined and appeared as small isolated clusters surrounded by gelatinous
      matrix. Notochordal nucleus pulposus cells from pig, phenotypically similar to
      human infant nucleus pulposus cells, were all CK8-positive. The mesenchymal
      intermediate filament protein vimentin was present in all bovine and porcine
      nucleus pulposus cells. CONCLUSIONS: The notochordal cell population is reported
      to disappear from the nucleus pulposus of bovine discs before birth and from
      human discs in childhood. However our finding of the co-expression of vimentin
      and CK8 in small isolated clusters of the bovine nucleus pulposus cells indicates
      that a subpopulation of notochordal-like cells remains in the mature bovine disc.
      This finding agrees with reports in the literature on co-expression of
      cytokeratins and vimentin in adult human discs. As notochordal cells produce
      factors that promote matrix production, the CK8-positive subpopulation could have
      important implications for activity and survival of the nucleus pulposus, and
      should be considered in development of cell therapies for disc repair. In
      addition, the finding of differential expression of proteins in the cell
      population of nucleus pulposus has implications with regard to the search for
      specific markers.

PMID- 20152016
TI  - Evaluation of chloroquine therapy for vivax and falciparum malaria in southern
      Sumatra, western Indonesia.
AB  - BACKGROUND: Chloroquine was used as first-line treatment for Plasmodium
      falciparum or Plasmodium vivax in Indonesia before the initial launch of
      artemisinin combination therapy in 2004. A study to evaluate efficacies of
      chloroquine against P. falciparum and P. vivax was undertaken at Lampung in
      southern Sumatra, western Indonesia in 2002. METHODS: Patients infected by P.
      falciparum or P. vivax were treated with 25 mg/kg chloroquine base in three daily
      doses over 48 hr. Finger prick blood was collected on Days 0, 2, 3, 7, 14, 21 and
      28 after starting drug administration. Whole blood chloroquine and its desethyl
      metabolite were measured on Days-0, -3 and -28, or on the day of recurrent
      parasitaemia. RESULTS: 42 patients infected by P. falciparum were enrolled, and
      38 fullfilled criteria for per protocol analysis. Only six of 38 (16%) showed a
      response consistent with senstivity to chloroquine. 25 of 32 failures were
      confirmed resistant by demonstrating chloroquine levels on day of recurrence
      exceeding the minimally effective concentration (200 ng/mL whole blood). The 28
      day cumulative incidence of resistance in P. falciparum was 68% (95% CI: 0.5260 -
      0.8306). Thirty one patients infected by P. vivax were enrolled, and 23 were
      evaluable for per protocol analysis. 15 out of 23 (65%) subjects had persistent
      or recurrent parasitaemia. Measurement of chloroquine levels confirmed all
      treatment failures prior to Day-15 as resistant. Beyond Day-15, 4 of 7
      recurrences also had drug levels above 100 ng/mL and were classified as
      resistant. The 28-day cumulative incidence of chloroquine resistance in P. vivax
      was 43% (95% CI: 0.2715 - 0.6384). CONCLUSION: These findings confirm
      persistantly high levels of resistance to chloroquine by P. falciparum in
      southern Sumatra, and suggest that high-grade and frequent resistance to
      chloroquine by P. vivax may be spreading westward in the Indonesia archipelago.

PMID- 20152017
TI  - Reduction of oxidative cellular damage by overexpression of the thioredoxin TRX2
      gene improves yield and quality of wine yeast dry active biomass.
AB  - BACKGROUND: Wine Saccharomyces cerevisiae strains, adapted to anaerobic must
      fermentations, suffer oxidative stress when they are grown under aerobic
      conditions for biomass propagation in the industrial process of active dry yeast
      production. Oxidative metabolism of sugars favors high biomass yields but also
      causes increased oxidation damage of cell components. The overexpression of the
      TRX2 gene, coding for a thioredoxin, enhances oxidative stress resistance in a
      wine yeast strain model. The thioredoxin and also the glutathione/glutaredoxin
      system constitute the most important defense against oxidation. Trx2p is also
      involved in the regulation of Yap1p-driven transcriptional response against some
      reactive oxygen species. RESULTS: Laboratory scale simulations of the industrial
      active dry biomass production process demonstrate that TRX2 overexpression
      increases the wine yeast final biomass yield and also its fermentative capacity
      both after the batch and fed-batch phases. Microvinifications carried out with
      the modified strain show a fast start phenotype derived from its enhanced
      fermentative capacity and also increased content of beneficial aroma compounds.
      The modified strain displays an increased transcriptional response of Yap1p
      regulated genes and other oxidative stress related genes. Activities of
      antioxidant enzymes like Sod1p, Sod2p and catalase are also enhanced.
      Consequently, diminished oxidation of lipids and proteins is observed in the
      modified strain, which can explain the improved performance of the thioredoxin
      overexpressing strain. CONCLUSIONS: We report several beneficial effects of
      overexpressing the thioredoxin gene TRX2 in a wine yeast strain. We show that
      this strain presents an enhanced redox defense. Increased yield of biomass
      production process in TRX2 overexpressing strain can be of special interest for
      several industrial applications.

PMID- 20152018
TI  - Scaling up community-based obesity prevention in Australia: background and
      evaluation design of the Health Promoting Communities: Being Active Eating Well
      initiative.
AB  - BACKGROUND: There is only limited evidence available on how best to prevent
      childhood obesity and community-based interventions hold promise, as several
      successful interventions have now been published. The Victorian Government has
      recently funded six disadvantaged communities across Victoria, Australia for
      three years to promote healthy eating and physical activity for children,
      families, and adults in a community-based participatory manner. Five of these
      intervention communities are situated in Primary Care Partnerships and are the
      subject of this paper. The interventions will comprise a mixture of capacity
      building, environmental, and whole-of-community approaches with targeted and
      population-level interventions. The specific intervention activities will be
      determined locally within each community through stakeholder and community
      consultation. Implementation of the interventions will occur through funded
      positions in primary care and local government. This paper describes the design
      of the evaluation of the five primary care partnership-based initiatives in the
      'Go for your life' Health Promoting Communities: Being Active Eating Well
      (HPC:BAEW) initiative. METHODS/DESIGN: A mixed method and multi-level evaluation
      of the HPC:BAEW initiative will capture process, impact and outcome data and
      involve both local and state-wide evaluators. There will be a combined analysis
      across the five community intervention projects with outcomes compared to a
      comparison group using a cross-sectional, quasi-experimental design. The
      evaluation will capture process, weight status, socio-demographic, obesity
      related behavioral and environmental data in intervention and comparison areas.
      This will be achieved using document analysis, paper-based questionnaires,
      interviews and direct measures of weight, height and waist circumference from
      participants (children, adolescents and adults). DISCUSSION: This study will add
      significant evidence on how to prevent obesity at a population level in
      disadvantaged and ethnically diverse communities. The outcomes will have direct
      influence on policy and practice and guide the development and implementation of
      future obesity prevention efforts in Australia and internationally. TRIAL
      REGISTRATION: ACTRN12609000892213.

PMID- 20152019
TI  - Emergency open cholecystectomy is associated with markedly lower incidence of
      postoperative nausea and vomiting (PONV) than elective open cholecystectomy: a
      retrospective cohort study.
AB  - BACKGROUND: During a previous study to define and compare incidence risks of
      postoperative nausea and vomiting (PONV) for elective laparoscopic and open
      cholecystectomy at two hospitals in Jamaica, secondary analysis comparing PONV
      risk in elective open cholecystectomy to that after emergency open
      cholecystectomy suggested that it was markedly reduced in the latter group. The
      decision was made to collect data on an adequate sample of emergency open
      cholecystectomy cases and further explore this unexpected finding in a separate
      study. METHODS: Data were collected for 91 emergency open cholecystomy cases
      identified at the two participating hospitals from May 2007 retrograde, as was
      done for the 175 elective open cholecystectomy cases (from the aforementioned
      study) with which the emergency cases were to be compared. Variables selected for
      extraction and statistical analysis included all those known, suspected and
      plausibly associated with the risk of PONV and with urgency of surgery. RESULTS:
      Emergency open cholecystectomy was associated with a markedly reduced incidence
      risk of PONV compared to elective open cholecystectomy (6.6% versus 28.6%, P <
      0.001). The suppressive effect of emergency increased after adjustment for
      confounders in a multivariable logistic regression model (odds ratio 0.103, P <
      0.001). This finding also identifies, by extrapolation, an association between
      reduced risk of PONV and preoperative nausea and vomiting, which occurred in
      80.2% of emergency cases in the 72 hour period preceding surgery. CONCLUSIONS:
      The incidence risk of postoperative nausea and vomiting is markedly decreased
      after emergency open cholecystectomy compared to elective open cholecystectomy.
      The study, by extrapolation, also identifies a paradoxical association between
      pre-operative nausea and vomiting, observed in 80.2% of emergency cases, and
      suppression of PONV. This association, if confirmed in prospective cohort
      studies, may have implications for PONV prophylaxis if it can be exploited at a
      sub-clinical level.

PMID- 20152020
TI  - Enrichment of homologs in insignificant BLAST hits by co-complex network
      alignment.
AB  - BACKGROUND: Homology is a crucial concept in comparative genomics. The algorithm
      probably most widely used for homology detection in comparative genomics, is
      BLAST. Usually a stringent score cutoff is applied to distinguish putative
      homologs from possible false positive hits. As a consequence, some BLAST hits are
      discarded that are in fact homologous. RESULTS: Analogous to the use of the
      genomics context in genome alignments, we test whether conserved functional
      context can be used to select candidate homologs from insignificant BLAST hits.
      We make a co-complex network alignment between complex subunits in yeast and
      human and find that proteins with an insignificant BLAST hit that are part of
      homologous complexes, are likely to be homologous themselves. Further analysis of
      the distant homologs we recovered using the co-complex network alignment, shows
      that a large majority of these distant homologs are in fact ancient paralogs.
      CONCLUSIONS: Our results show that, even though evolution takes place at the
      sequence and genome level, co-complex networks can be used as circumstantial
      evidence to improve confidence in the homology of distantly related sequences.

PMID- 20152021
TI  - Diffusion-weighted magnetic resonance imaging for predicting the clinical outcome
      of comatose survivors after cardiac arrest: a cohort study.
AB  - INTRODUCTION: The aim of this study was to examine whether the patterns of
      diffusion-weighted imaging (DWI) abnormalities and quantitative regional apparent
      diffusion coefficient (ADC) values can predict the clinical outcome of comatose
      patients following cardiac arrest. METHODS: Thirty-nine patients resuscitated
      from out-of-hospital cardiac arrest were prospectively investigated. Within five
      days of resuscitation, axial DWIs were obtained and ADC maps were generated using
      two 1.5-T magnetic resonance scanners. The neurological outcomes of the patients
      were assessed using the Glasgow Outcome Scale (GOS) score at three months after
      the cardiac arrest. The brain injuries were categorised into four patterns:
      normal, isolated cortical injury, isolated deep grey nuclei injury, and mixed
      injuries (cortex and deep grey nuclei). Twenty-three subjects with normal DWIs
      served as controls. The ADC and percent ADC values (the ADC percentage as
      compared to the control data from the corresponding region) were obtained in
      various regions of the brains. We analysed the differences between the favourable
      (GOS score 4 to 5) and unfavourable (GOS score 1 to 3) groups with regard to
      clinical data, the DWI abnormalities, and the ADC and percent ADC values.
      RESULTS: The restricted diffusion abnormalities in the cerebral cortex, caudate
      nucleus, putamen and thalamus were significantly different between the favourable
      (n = 13) and unfavourable (n = 26) outcome groups. The cortical pattern of injury
      was seen in one patient (3%), the deep grey nuclei pattern in three patients
      (8%), the cortex and deep grey nuclei pattern in 21 patients (54%), and normal
      DWI findings in 14 patients (36%). The cortex and deep grey nuclei pattern was
      significantly associated with the unfavourable outcome (20 patients with
      unfavourable vs. 1 patient with favourable outcomes, P < 0.001). In the 22
      patients with quantitative ADC analyses, severely reduced ADCs were noted in the
      unfavourable outcome group. The optimal cutoffs for the mean ADC and the percent
      ADC values determined by receiver operating characteristic (ROC) curve analysis
      in the cortex, caudate nucleus, putamen, and thalamus predicted the unfavourable
      outcome with sensitivities of 67 to 93% and a specificity of 100%. CONCLUSIONS:
      The patterns of brain injury in early diffusion-weighted imaging (DWI) (less than
      or equal to five days after resuscitation) and the quantitative measurement of
      regional ADC may be useful for predicting the clinical outcome of comatose
      patients after cardiac arrest.

PMID- 20152022
TI  - Effects of a mouthwash with chlorine dioxide on oral malodor and salivary
      bacteria: a randomized placebo-controlled 7-day trial.
AB  - BACKGROUND: Previous research has shown the oxidizing properties and
      microbiological efficacies of chlorine dioxide (ClO2). Its clinical efficacies on
      oral malodor have been evaluated and reported only in short duration trials,
      moreover, no clinical studies have investigated its microbiological efficacies on
      periodontal and malodorous bacteria. Thus, the aim of this study was to assess
      the inhibitory effects of a mouthwash containing ClO2 used for 7 days on morning
      oral malodor and on salivary periodontal and malodorous bacteria. METHODS/DESIGN:
      A randomized, double blind, crossover, placebo-controlled trial was conducted
      among 15 healthy male volunteers, who were divided into 2 groups. Subjects were
      instructed to rinse with the experimental mouthwash containing ClO2 or the
      placebo mouthwash, without ClO2, twice per day for 7 days. After a one week
      washout period, each group then used the opposite mouthwash for 7 days. At
      baseline and after 7 days, oral malodor was evaluated with Organoleptic
      measurement (OM), and analyzed the concentrations of hydrogen sulfide (H2S),
      methyl mercaptan (CH3SH) and dimethyl sulfide ((CH3)2S), the main VSCs of human
      oral malodor, were assessed by gas chromatography (GC). Clinical outcome
      variables included plaque and gingival indices, and tongue coating index. The
      samples of saliva were microbiologically investigated. Quantitative and
      qualitative analyses were performed using the polymerase chain reaction-Invader
      method. RESULTS AND DISCUSSION: The baseline oral condition in healthy subjects
      in the 2 groups did not differ significantly. After rinsing with the mouthwash
      containing ClO2 for 7 days, morning bad breath decreased as measured by the OM
      and reduced the concentrations of H2S, CH3SH and (CH3)2S measured by GC, were
      found. Moreover ClO2 mouthwash used over a 7-day period appeared effective in
      reducing plaque, tongue coating accumulation and the counts of Fusobacterium
      nucleatum in saliva. Future research is needed to examine long-term effects, as
      well as effects on periodontal diseases and plaque accumulation in a well-defined
      sample of halitosis patients and broader population samples. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00748943.

PMID- 20152023
TI  - Perceived connections between information and communication technology use and
      mental symptoms among young adults - a qualitative study.
AB  - BACKGROUND: Prospective associations have been found between high use of
      information and communication technology (ICT) and reported mental symptoms among
      young adult university students, but the causal mechanisms are unclear. Our aim
      was to explore possible explanations for associations between high ICT use and
      symptoms of depression, sleep disorders, and stress among young adults in order
      to propose a model of possible pathways to mental health effects that can be
      tested epidemiologically. METHODS: We conducted a qualitative interview study
      with 16 women and 16 men (21-28 years), recruited from a cohort of university
      students on the basis of reporting high computer (n = 28) or mobile phone (n =
      20) use at baseline and reporting mental symptoms at the one-year follow-up. Semi
      structured interviews were performed, with open-ended questions about possible
      connections between the use of computers and mobile phones, and stress,
      depression, and sleep disturbances. The interview data were analyzed with
      qualitative content analysis and summarized in a model. RESULTS: Central factors
      appearing to explain high quantitative ICT use were personal dependency, and
      demands for achievement and availability originating from the domains of work,
      study, social life, and individual aspirations. Consequences included mental
      overload, neglect of other activities and personal needs, time pressure, role
      conflicts, guilt feelings, social isolation, physical symptoms, worry about
      electromagnetic radiation, and economic problems. Qualitative aspects
      (destructive communication and information) were also reported, with consequences
      including vulnerability, misunderstandings, altered values, and feelings of
      inadequacy. User problems were a source of frustration. Altered ICT use as an
      effect of mental symptoms was reported, as well as possible positive effects of
      ICT on mental health. CONCLUSIONS: The concepts and ideas of the young adults
      with high ICT use and mental symptoms generated a model of possible paths for
      associations between ICT exposure and mental symptoms. Demands for achievement
      and availability as well as personal dependency were major causes of high ICT
      exposure but also direct sources of stress and mental symptoms. The proposed
      model shows that factors in different domains may have an impact and should be
      considered in epidemiological and intervention studies.

PMID- 20152024
TI  - Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving
      chemotherapy: prospective, randomized, pilot clinical study.
AB  - BACKGROUND: Prospective, randomized, pilot clinical study was conducted to
      evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in
      breast cancer patients treated with adjuvant therapy. PATIENTS AND METHODS:
      Patients with invasive ductal breast cancer where polychemotherapy was indicated
      were monitored in the period from 2005-2007. Fourteen patients in the same stage
      of ductal invasive breast cancer were involved in the study, divided in two
      randomized groups. One group was subjected to take IP6 + Inositol while the other
      group was taking placebo. In both groups of patients the same laboratory
      parameters were monitored. When the treatment was finished, all patients have
      filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life.
      RESULTS: Patients receiving chemotherapy, along with IP6 + Inositol did not have
      cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor
      markers were unaltered in both groups. However, patients who took IP6 + Inositol
      had significantly better quality of life (p = 0.05) and functional status (p =
      0.0003) and were able to perform their daily activities. CONCLUSION: IP6 +
      Inositol as an adjunctive therapy is valuable help in ameliorating the side
      effects and preserving quality of life among the patients treated with
      chemotherapy.

PMID- 20152025
TI  - Genomics based analysis of interactions between developing B-lymphocytes and
      stromal cells reveal complex interactions and two-way communication.
AB  - BACKGROUND: The use of functional genomics has largely increased our
      understanding of cell biology and promises to help the development of systems
      biology needed to understand the complex order of events that regulates cellular
      differentiation in vivo. One model system clearly dependent on the integration of
      extra and intra cellular signals is the development of B-lymphocytes from
      hematopoietic stem cells in the bone marrow. This developmental pathway involves
      several defined differentiation stages associated with specific expression of
      genes including surface markers that can be used for the prospective isolation of
      the progenitor cells directly from the bone marrow to allow for ex vivo gene
      expression analysis. The developmental process can be simulated in vitro making
      it possible to dissect information about cell/cell communication as well as to
      address the relevance of communication pathways in a rather direct manner. Thus
      we believe that B-lymphocyte development represents a useful model system to take
      the first steps towards systems biology investigations in the bone marrow.
      RESULTS: In order to identify extra cellular signals that promote B lymphocyte
      development we created a database with approximately 400 receptor ligand pairs
      and software matching gene expression data from two cell populations to obtain
      information about possible communication pathways. Using this database and gene
      expression data from NIH3T3 cells (unable to support B cell development), OP-9
      cells (strongly supportive of B cell development), pro-B and pre-B cells as well
      as mature peripheral B-lineage cells, we were able to identify a set of potential
      stage and stromal cell restricted communication pathways. Functional analysis of
      some of these potential ways of communication allowed us to identify BMP-4 as a
      potent stimulator of B-cell development in vitro. Further, the analysis suggested
      that there existed possibilities for progenitor B cells to send signals to the
      stroma. The functional consequences of this were investigated by co-culture
      experiments revealing that the co-incubation of stromal cells with B cell
      progenitors altered both the morphology and the gene expression pattern in the
      stromal cells. CONCLUSIONS: We believe that this gene expression data analysis
      method allows for the identification of functionally relevant interactions and
      therefore could be applied to other data sets to unravel novel communication
      pathways.

PMID- 20152026
TI  - Semi-automatic quantification of 4D left ventricular blood flow.
AB  - BACKGROUND: The beating heart is the generator of blood flow through the
      cardiovascular system. Within the heart's own chambers, normal complex blood flow
      patterns can be disturbed by diseases. Methods for the quantification of intra
      cardiac blood flow, with its 4D (3D+time) nature, are lacking. We sought to
      develop and validate a novel semi-automatic analysis approach that integrates
      flow and morphological data. METHOD: In six healthy subjects and three patients
      with dilated cardiomyopathy, three-directional, three-dimensional cine phase
      contrast cardiovascular magnetic resonance (CMR) velocity data and balanced
      steady-state free-precession long- and short-axis images were acquired. The LV
      endocardium was segmented from the short-axis images at the times of
      isovolumetric contraction (IVC) and isovolumetric relaxation (IVR). At the time
      of IVC, pathlines were emitted from the IVC LV blood volume and traced forwards
      and backwards in time until IVR, thus including the entire cardiac cycle. The IVR
      volume was used to determine if and where the pathlines left the LV. This
      information was used to automatically separate the pathlines into four different
      components of flow: Direct Flow, Retained Inflow, Delayed Ejection Flow and
      Residual Volume. Blood volumes were calculated for every component by multiplying
      the number of pathlines with the blood volume represented by each pathline. The
      accuracy and inter- and intra-observer reproducibility of the approach were
      evaluated by analyzing volumes of LV inflow and outflow, the four flow
      components, and the end-diastolic volume. RESULTS: The volume and distribution of
      the LV flow components were determined in all subjects. The calculated LV outflow
      volumes [ml] (67 +/- 13) appeared to fall in between those obtained by through
      plane phase-contrast CMR (77 +/- 16) and Doppler ultrasound (58 +/- 10),
      respectively. Calculated volumes of LV inflow (68 +/- 11) and outflow (67 +/- 13)
      were well matched (NS). Low inter- and intra-observer variability for the
      assessment of the volumes of the flow components was obtained. CONCLUSIONS: This
      semi-automatic analysis approach for the quantification of 4D blood flow resulted
      in accurate LV inflow and outflow volumes and a high reproducibility for the
      assessment of LV flow components.

PMID- 20152027
TI  - Correction: High throughput approaches reveal splicing of primary microRNA
      transcripts and tissue specific expression of mature microRNAs in Vitis vinifera.
AB  - The version of this article published in BMC Genomics 2009, 10:558, contains data
      in Table 1 which are now known to be unreliable, and an illustration, in Figure
      1, of unusual miRNA processing events predicted by these unreliable data. In this
      full-length correction, new data replace those found to be unreliable, leading to
      a more straightforward interpretation without altering the principle conclusions
      of the study. Table 1 and associated methods have been corrected, Figure 1
      deleted, supplementary file 1 added, and modifications made to the sections "Deep
      sequencing of small RNAs from grapevine leaf tissue" and "Microarray analysis of
      miRNA expression". The editors and authors regret the inconvenience caused to
      readers by premature publication of the original paper. BACKGROUND: MicroRNAs are
      short (~21 base) single stranded RNAs that, in plants, are generally coded by
      specific genes and cleaved specifically from hairpin precursors. MicroRNAs are
      critical for the regulation of multiple developmental, stress related and other
      physiological processes in plants. The recent annotation of the genome of the
      grapevine (Vitis vinifera L.) allowed the identification of many putative
      conserved microRNA precursors, grouped into multiple gene families. RESULTS: Here
      we use oligonucleotide arrays to provide the first indication that many of these
      microRNAs show differential expression patterns between tissues and during the
      maturation of fruit in the grapevine. Furthermore we demonstrate that whole
      transcriptome sequencing and deep-sequencing of small RNA fractions can be used
      both to identify which microRNA precursors are expressed in different tissues and
      to estimate genomic coordinates and patterns of splicing and alternative splicing
      for many primary miRNA transcripts. CONCLUSIONS: Our results show that many
      microRNAs are differentially expressed in different tissues and during fruit
      maturation in the grapevine. Furthermore, the demonstration that whole
      transcriptome sequencing can be used to identify candidate splicing events and
      approximate primary microRNA transcript coordinates represents a significant step
      towards the large-scale elucidation of mechanisms regulating the expression of
      microRNAs at the transcriptional and post-transcriptional levels.

PMID- 20152028
TI  - BMP-2 functions independently of SHH signaling and triggers cell condensation and
      apoptosis in regenerating axolotl limbs.
AB  - BACKGROUND: Axolotls have the unique ability, among vertebrates, to perfectly
      regenerate complex body parts, such as limbs, after amputation. In addition,
      axolotls pattern developing and regenerating autopods from the anterior to
      posterior axis instead of posterior to anterior like all tetrapods studied to
      date. Sonic hedgehog is important in establishing this anterior-posterior axis of
      limbs in all tetrapods including axolotls. Interestingly, its expression is
      conserved (to the posterior side of limb buds and blastemas) in axolotl limbs as
      in other tetrapods. It has been suggested that BMP-2 may be the secondary
      mediator of sonic hedgehog, although there is mounting evidence to the contrary
      in mice. Since BMP-2 expression is on the anterior portion of developing and
      regenerating limbs prior to digit patterning, opposite to the expression of sonic
      hedgehog, we examined whether BMP-2 expression was dependent on sonic hedgehog
      signaling and whether it affects patterning of the autopod during regeneration.
      RESULTS: The expression of BMP-2 and SOX-9 in developing and regenerating axolotl
      limbs corresponded to the first digits forming in the anterior portion of the
      autopods. The inhibition of sonic hedgehog signaling with cyclopamine caused
      hypomorphic limbs (during development and regeneration) but did not affect the
      expression of BMP-2 and SOX-9. Overexpression of BMP-2 in regenerating limbs
      caused a loss of digits. Overexpression of Noggin (BMP inhibitor) in regenerating
      limbs also resulted in a loss of digits. Histological analysis indicated that the
      loss due to BMP-2 overexpression was the result of increased cell condensation
      and apoptosis while the loss caused by Noggin was due to a decrease in cell
      division. CONCLUSION: The expression of BMP-2 and its target SOX-9 was
      independent of sonic hedgehog signaling in developing and regenerating limbs.
      Their expression correlated with chondrogenesis and the appearance of skeletal
      elements has described in other tetrapods. Overexpression of BMP-2 did not cause
      the formation of extra digits, which is consistent with the hypothesis that it is
      not the secondary signal of sonic hedgehog. However, it did cause the formation
      of hypomorphic limbs as a result of increased cellular condensation and
      apoptosis. Taken together, these results suggest that BMP-2 does not have a
      direct role in patterning regenerating limbs but may be important to trigger
      condensation prior to ossification and to mediate apoptosis.

PMID- 20152029
TI  - The effect of an external magnetic force on cell adhesion and proliferation of
      magnetically labeled mesenchymal stem cells.
AB  - BACKGROUND: As the strategy for tissue regeneration using mesenchymal stem cells
      (MSCs) for transplantation, it is necessary that MSCs be accumulated and kept in
      the target area. To accumulate MSCs effectively, we developed a novel technique
      for a magnetic targeting system with magnetically labeled MSCs and an external
      magnetic force. In this study, we examined the effect of an external magnetic
      force on magnetically labeled MSCs in terms of cell adhesion and proliferation.
      METHODS: Magnetically labeled MSCs were plated at the bottom of an insert under
      the influence of an external magnetic force for 1 hour. Then the inserts were
      turned upside down for between 1 and 24 hours, and the number of MSCs which had
      fallen from the membrane was counted. The gene expression of MSCs affected
      magnetic force was analyzed with microarray. In the control group, the same
      procedure was done without the external magnetic force. RESULTS: At 1 hour after
      the inserts were turned upside down, the average number of fallen MSCs in the
      magnetic group was significantly smaller than that in the control group,
      indicating enhanced cell adhesion. At 24 hours, the average number of fallen MSCs
      in the magnetic group was also significantly smaller than that in control group.
      In the magnetic group, integrin alpha2, alpha6, beta3 BP, intercellular adhesion
      molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1) were
      upregulated. At 1, 2 and 3 weeks after incubation, there was no statistical
      significant difference in the numbers of MSCs in the magnetic group and control
      group. CONCLUSIONS: The results indicate that an external magnetic force for 1
      hour enhances cell adhesion of MSCs. Moreover, there is no difference in cell
      proliferation after using an external magnetic force on magnetically labeled
      MSCs.

PMID- 20152030
TI  - Incidence of oral cancer in relation to nickel and arsenic concentrations in farm
      soils of patients' residential areas in Taiwan.
AB  - BACKGROUND: To explore if exposures to specific heavy metals in the environment
      is a new risk factor of oral cancer, one of the fastest growing malignancies in
      Taiwan, in addition to the two established risk factors, cigarette smoking and
      betel quid chewing. METHODS: This is an observational study utilized the age
      standardized incidence rates of oral cancer in the 316 townships and precincts of
      Taiwan, local prevalence rates of cigarette smoking and betel quid chewing,
      demographic factors, socio-economic conditions, and concentrations in farm soils
      of the eight kinds of heavy metal. Spatial regression and GIS (Geographic
      Information System) were used. The registration contained 22,083 patients, who
      were diagnosed with oral cancer between 1982 and 2002. The concentrations of
      metal in the soils were retrieved from a nation-wide survey in the 1980s.
      RESULTS: The incidence rate of oral cancer is geographically related to the
      concentrations of arsenic and nickel in the patients' residential areas, with the
      prevalence of cigarette smoking and betel quid chewing as controlled variables.
      CONCLUSIONS: Beside the two established risk factors, cigarette smoking and betel
      quid chewing, arsenic and nickel in farm soils may be new risk factors for oral
      cancer. These two kinds of metal may involve in the development of oral cancer.
      Further studies are required to understand the pathways via which metal in the
      farm soils exerts its effects on human health.

PMID- 20152031
TI  - Development of a patient reported outcome scale for fatigue in multiple
      sclerosis: The Neurological Fatigue Index (NFI-MS).
AB  - BACKGROUND: Fatigue is a common and debilitating symptom in multiple sclerosis
      (MS). Best-practice guidelines suggest that health services should repeatedly
      assess fatigue in persons with MS. Several fatigue scales are available but
      concern has been expressed about their validity. The objective of this study was
      to examine the reliability and validity of a new scale for MS fatigue, the
      Neurological Fatigue Index (NFI-MS). METHODS: Qualitative analysis of 40 MS
      patient interviews had previously contributed to a coherent definition of
      fatigue, and a potential 52 item set representing the salient themes. A draft
      questionnaire was mailed out to 1223 people with MS, and the resulting data
      subjected to both factor and Rasch analysis. RESULTS: Data from 635 (51.9%
      response) respondents were split randomly into an 'evaluation' and 'validation'
      sample. Exploratory factor analysis identified four potential subscales:
      'physical', 'cognitive', 'relief by diurnal sleep or rest' and 'abnormal
      nocturnal sleep and sleepiness'. Rasch analysis led to further item reduction and
      the generation of a Summary scale comprising items from the Physical and
      Cognitive subscales. The scales were shown to fit Rasch model expectations,
      across both the evaluation and validation samples. CONCLUSION: A simple 10-item
      Summary scale, together with scales measuring the physical and cognitive
      components of fatigue, were validated for MS fatigue.

PMID- 20152032
TI  - Comparative analyses reveal distinct sets of lineage-specific genes within
      Arabidopsis thaliana.
AB  - BACKGROUND: The availability of genome and transcriptome sequences for a number
      of species permits the identification and characterization of conserved as well
      as divergent genes such as lineage-specific genes which have no detectable
      sequence similarity to genes from other lineages. While genes conserved among
      taxa provide insight into the core processes among species, lineage-specific
      genes provide insights into evolutionary processes and biological functions that
      are likely clade or species specific. RESULTS: Comparative analyses using the
      Arabidopsis thaliana genome and sequences from 178 other species within the Plant
      Kingdom enabled the identification of 24,624 A. thaliana genes (91.7%) that were
      termed Evolutionary Conserved (EC) as defined by sequence similarity to a
      database entry as well as two sets of lineage-specific genes within A. thaliana.
      One of the A. thaliana lineage-specific gene sets share sequence similarity only
      to sequences from species within the Brassicaceae family and are termed Conserved
      Brassicaceae-Specific Genes (914, 3.4%, CBSG). The other set of A. thaliana
      lineage-specific genes, the Arabidopsis Lineage-Specific Genes (1,324, 4.9%,
      ALSG), lack sequence similarity to any sequence outside A. thaliana. While many
      CBSGs (76.7%) and ALSGs (52.9%) are transcribed, the majority of the CBSGs
      (76.1%) and ALSGs (94.4%) have no annotated function. Co-expression analysis
      indicated significant enrichment of the CBSGs and ALSGs in multiple functional
      categories suggesting their involvement in a wide range of biological functions.
      Subcellular localization prediction revealed that the CBSGs were significantly
      enriched in proteins targeted to the secretory pathway (412, 45.1%). Among the
      107 putatively secreted CBSGs with known functions, 67 encode a putative pollen
      coat protein or cysteine-rich protein with sequence similarity to the S-locus
      cysteine-rich protein that is the pollen determinant controlling allele specific
      pollen rejection in self-incompatible Brassicaceae species. Overall, the ALSGs
      and CBSGs were more highly methylated in floral tissue compared to the ECs.
      Single Nucleotide Polymorphism (SNP) analysis showed an elevated ratio of non
      synonymous to synonymous SNPs within the ALSGs (1.99) and CBSGs (1.65) relative
      to the EC set (0.92), mainly caused by an elevated number of non-synonymous SNPs,
      indicating that they are fast-evolving at the protein sequence level.
      CONCLUSIONS: Our analyses suggest that while a significant fraction of the A.
      thaliana proteome is conserved within the Plant Kingdom, evolutionarily distinct
      sets of genes that may function in defining biological processes unique to these
      lineages have arisen within the Brassicaceae and A. thaliana.

PMID- 20152034
TI  - Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of
      cancer among children in Malawi - preliminary findings.
AB  - BACKGROUND: The impact of infection with HIV on the risk of cancer in children is
      uncertain, particularly for those living in sub-Saharan Africa. In an ongoing
      study in a paediatric oncology centre in Malawi, children (aged </= 15 years)
      with known or suspected cancers are being recruited and tested for HIV and their
      mothers or carers interviewed. This study reports findings for children recruited
      between 2005 and 2008. METHODS: Only children with a cancer diagnosis were
      included. Odds ratios (OR) for being HIV positive were estimated for each cancer
      type (with adjustment for age (<5 years, >/= 5 years) and sex) using children
      with other cancers and non-malignant conditions as a comparison group (excluding
      the known HIV-associated cancers, Kaposi sarcoma and lymphomas, as well as
      children with other haematological malignancies or with confirmed non-cancer
      diagnoses). RESULTS: Of the 586 children recruited, 541 (92%) met the inclusion
      criteria and 525 (97%) were tested for HIV. Overall HIV seroprevalence was 10%.
      Infection with HIV was associated with Kaposi sarcoma (29 cases; OR = 93.5, 95%
      CI 26.9 to 324.4) and with non-Burkitt, non-Hodgkin lymphoma (33 cases; OR = 4.4,
      95% CI 1.1 to 17.9) but not with Burkitt lymphoma (269 cases; OR = 2.2, 95% CI
      0.8 to 6.4). CONCLUSIONS: In this study, only Kaposi sarcoma and non-Burkitt, non
      Hodgkin lymphoma were associated with HIV infection. The endemic form of Burkitt
      lymphoma, which is relatively frequent in Malawi, was not significantly
      associated with HIV. While the relatively small numbers of children with other
      cancers, together with possible limitations of diagnostic testing may limit our
      conclusions, the findings may suggest differences in the pathogenesis of HIV
      related malignancies in different parts of the world.

PMID- 20152033
TI  - Expression of cell cycle proteins in male breast carcinoma.
AB  - INTRODUCTION: Male breast cancer (MBC) is a rare, yet potentially aggressive
      disease. Although literature regarding female breast cancer (FBC) is extensive,
      little is known about the etiopathogenesis of male breast cancer. Studies from
      our laboratory show that MBCs have a distinct immunophenotypic profile,
      suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of
      this study was to evaluate and correlate the immunohistochemical expression of
      cell cycle proteins in male breast carcinoma to significant clinico-biological
      endpoints. METHODS: 75 cases of MBC were identified using the records of the
      Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and
      analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57,
      p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor
      size, node status, stage of the disease, and disease free survival (DFS).
      RESULTS: Decreased DFS was observed in the majority of tumors that overexpressed
      PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the
      expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was
      overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm
      (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p =
      0.04) and were associated with increased DFS of >150 months (p = 0.04).
      Overexpression of c-myc (90%) was linked with a higher incidence of node
      negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression
      was associated with decreased lymph node metastasis (p = 0.04). P21 and p57
      positive tumors were related to decreased DFS (p = 0.04). Though p16 was
      overexpressed in 76.6%, this did not reach statistical significance with DFS (p =
      0.06) or nodal status (p = 0.07). CONCLUSION: Aberrant cell cycle protein
      expression supports our view that these are important pathways involved in the
      etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had
      better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA
      with significantly worse outcomes. P27 appears to be a predictive marker for
      lymph nodal status. Such observation strongly suggests that dysregulation of cell
      cycle proteins may play a unique role in the initiation and progression of
      disease in male breast cancer. Such findings open up new avenues for the
      treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies
      in the future.

PMID- 20152035
TI  - Sindbis viral vector induced apoptosis requires translational inhibition and
      signaling through Mcl-1 and Bak.
AB  - BACKGROUND: Sindbis viral vectors are able to efficiently target and kill tumor
      cells in vivo, as shown using pancreatic and ovarian cancer models. Infection
      results in apoptosis both in vitro and in vivo. Sindbis vector uptake is mediated
      by the LAMR, which is upregulated on a number of different tumor types, thus
      conferring specificity of the vector to a wide range of cancers. In this study we
      elucidate the mechanism of apoptosis in two tumor cell lines, MOSEC, derived from
      the ovarian epithelium and Pan02, derived from a pancreatic adenocarcinoma. A
      comprehensive understanding of the mechanism of apoptosis would facilitate the
      design of more effective vectors for cancer therapy. RESULTS: The initial phase
      of Sindbis vector induced apoptosis in MOSEC and Pan02 models reconfirms that
      viral infection is sensed by PKR due to double-stranded RNA intermediates
      associated with genomic replication. PKR activation results in translation
      inhibition through eIF2alpha phosphorylation and initiation of the stress
      response. Our studies indicate that the roles of two proteins, Mcl-1 and JNK,
      intimately link Sindbis induced translational arrest and cellular stress.
      Translational arrest inhibits the synthesis of anti-apoptotic Bcl-2 protein, Mcl
      1. JNK activation triggers the release of Bad from 14-3-3, which ultimately
      results in apoptosis. These signals from translational arrest and cellular stress
      are propagated to the mitochondria where Bad and Bik bind to Bcl-xl and Mcl-1
      respectively. Formation of these heterodimers displaces Bak, which results in
      caspase 9 cleavage and signaling through the mitochondrial pathway of apoptosis.
      CONCLUSION: The host cell response to Sindbis is triggered through PKR
      activation. Our studies demonstrate that PKR activation and subsequent
      translational arrest is linked to both cellular stress and apoptosis. We have
      also found the linkage point between translational arrest and apoptosis to be Mcl
      1, a protein whose constant translation is required for inhibition of apoptosis.
      With this information vectors can be designed, which express or repress proteins
      implicated in this study, to enhance their therapeutic potential.

PMID- 20152036
TI  - Polymorphisms in O-methyltransferase genes are associated with stover cell wall
      digestibility in European maize (Zea mays L.).
AB  - BACKGROUND: OMT (O-methyltransferase) genes are involved in lignin biosynthesis,
      which relates to stover cell wall digestibility. Reduced lignin content is an
      important determinant of both forage quality and ethanol conversion efficiency of
      maize stover. RESULTS: Variation in genomic sequences coding for COMT, CCoAOMT1,
      and CCoAOMT2 was analyzed in relation to stover cell wall digestibility for a
      panel of 40 European forage maize inbred lines, and re-analyzed for a panel of 34
      lines from a published French study. Different methodologies for association
      analysis were performed and compared. Across association methodologies, a total
      number of 25, 12, 1, 6 COMT polymorphic sites were significantly associated with
      DNDF, OMD, NDF, and WSC, respectively. Association analysis for CCoAOMT1 and
      CCoAOMT2 identified substantially fewer polymorphic sites (3 and 2, respectively)
      associated with the investigated traits. Our re-analysis on the 34 lines from a
      published French dataset identified 14 polymorphic sites significantly associated
      with cell wall digestibility, two of them were consistent with our study.
      Promising polymorphisms putatively causally associated with variability of cell
      wall digestibility were inferred from the total number of significantly
      associated SNPs/Indels. CONCLUSIONS: Several polymorphic sites for three O
      methyltransferase loci were associated with stover cell wall digestibility. All
      three tested genes seem to be involved in controlling DNDF, in particular COMT.
      Thus, considerable variation among Bm3 wildtype alleles can be exploited for
      improving cell-wall digestibility. Target sites for functional markers were
      identified enabling development of efficient marker-based selection strategies.

PMID- 20152037
TI  - Air pollution and mortality in the Canary Islands: a time-series analysis.
AB  - BACKGROUND: The island factor of the cities of Las Palmas de Gran Canaria and
      Santa Cruz de Tenerife, along with their proximity to Africa and their
      meteorology, create a particular setting that influences the air quality of these
      cities and provides researchers an opportunity to analyze the acute effects of
      air-pollutants on daily mortality. METHODS: From 2000 to 2004, the relationship
      between daily changes in PM10, PM2.5, SO2, NO2, CO, and ozone levels and daily
      total mortality and mortality due to respiratory and heart diseases were assessed
      using Generalized Additive Poisson models controlled for potential confounders.
      The lag effect (up to five days) as well as the concurrent and previous day
      averages and distributed lag models were all estimated. Single and two pollutant
      models were also constructed. RESULTS: Daily levels of PM10, PM2.5, NO2, and SO2
      were found to be associated with an increase in respiratory mortality in Santa
      Cruz de Tenerife and with increased heart disease mortality in Las Palmas de Gran
      Canaria, thus indicating an association between daily ozone levels and mortality
      from heart diseases. The effects spread over five successive days. SO2 was the
      only air pollutant significantly related with total mortality (lag 0).
      CONCLUSIONS: There is a short-term association between current exposure levels to
      air pollution and mortality (total as well as that due specifically to heart and
      respiratory diseases) in both cities. Risk coefficients were higher for
      respiratory and cardiovascular mortality, showing a delayed effect over several
      days.

PMID- 20152038
TI  - Lists2Networks: integrated analysis of gene/protein lists.
AB  - BACKGROUND: Systems biologists are faced with the difficulty of analyzing results
      from large-scale studies that profile the activity of many genes, RNAs and
      proteins, applied in different experiments, under different conditions, and
      reported in different publications. To address this challenge it is desirable to
      compare the results from different related studies such as mRNA expression
      microarrays, genome-wide ChIP-X, RNAi screens, proteomics and phosphoproteomics
      experiments in a coherent global framework. In addition, linking high-content
      multilayered experimental results with prior biological knowledge can be useful
      for identifying functional themes and form novel hypotheses. RESULTS: We present
      Lists2Networks, a web-based system that allows users to upload lists of mammalian
      genes/proteins onto a server-based program for integrated analysis. The system
      includes web-based tools to manipulate lists with different set operations, to
      expand lists using existing mammalian networks of protein-protein interactions,
      co-expression correlation, or background knowledge co-annotation correlation, as
      well as to apply gene-list enrichment analyses against many gene-list libraries
      of prior biological knowledge such as pathways, gene ontology terms, kinase
      substrate, microRNA-mRAN, and protein-protein interactions, metabolites, and
      protein domains. Such analyses can be applied to several lists at once against
      many prior knowledge libraries of gene-lists associated with specific
      annotations. The system also contains features that allow users to export
      networks and share lists with other users of the system. CONCLUSIONS:
      Lists2Networks is a user friendly web-based software system expected to
      significantly ease the computational analysis process for experimental systems
      biologists employing high-throughput experiments at multiple layers of
      regulation. The system is freely available at http://www.lists2networks.org.

PMID- 20152039
TI  - Spatial analysis of learning and developmental disorders in upper Cape Cod,
      Massachusetts using generalized additive models.
AB  - The spatial variability of three indicators of learning and developmental
      disability (LDD) was assessed for Cape Cod, Massachusetts. Maternal reports of
      receiving special education services, attention deficit hyperactivity disorder,
      and educational attainment were available for a birth cohort from 1969-1983.
      Using generalized additive models and residential history, maps of the odds of
      LDD were produced that also controlled for known risk factors. While results were
      not statistically significant, they suggest that children living in certain parts
      of Cape Cod were more likely to have a LDD. The spatial variation may be due to
      variation in the physical and social environment.

PMID- 20152040
TI  - In vitro and ex vivo effect of hyaluronic acid on erythrocyte flow properties.
AB  - BACKGROUND: Hyaluronic acid (HA) is present in many tissues; its presence in
      serum may be related to certain inflammatory conditions, tissue damage, sepsis,
      liver malfunction and some malignancies. In the present work, our goal was to
      investigate the significance of hyaluronic acid effect on erythrocyte flow
      properties. Therefore we performed in vitro experiments incubating red blood
      cells (RBCs) with several HA concentrations. Afterwards, in order to corroborate
      the pathophysiological significance of the results obtained, we replicated the in
      vitro experiment with ex vivo RBCs from diagnosed rheumatoid arthritis (RA)
      patients, a serum HA-increasing pathology. METHODS: Erythrocyte deformability (by
      filtration through nucleopore membranes) and erythrocyte aggregability (EA) were
      tested on blood from healthy donors additioned with purified HA. EA was measured
      by transmitted light and analyzed with a mathematical model yielding two
      parameters, the aggregation rate and the size of the aggregates. Conformational
      changes of cytoskeleton proteins were estimated by electron paramagnetic
      resonance spectroscopy (EPR). RESULTS: In vitro, erythrocytes treated with HA
      showed increased rigidity index (RI) and reduced aggregability, situation
      strongly related to the rigidization of the membrane cytoskeleton triggered by
      HA, as shown by EPR results. Also, a significant correlation (r: 0.77, p <
      0.00001) was found between RI and serum HA in RA patients. CONCLUSIONS: Our
      results lead us to postulate the hypothesis that HA interacts with the
      erythrocyte surface leading to modifications in erythrocyte rheological and flow
      properties, both ex vivo and in vitro.

PMID- 20152041
TI  - Using qualitative methods to inform the trade-off between content validity and
      consistency in utility assessment: the example of type 2 diabetes and Alzheimer's
      disease.
AB  - BACKGROUND: Key stakeholders regard generic utility instruments as suitable tools
      to inform health technology assessment decision-making regarding allocation of
      resources across competing interventions. These instruments require a
      'descriptor', a 'valuation' and a 'perspective' of the economic evaluation. There
      are various approaches that can be taken for each of these, offering a potential
      lack of consistency between instruments (a basic requirement for comparisons
      across diseases). The 'reference method' has been proposed as a way to address
      the limitations of the Quality-Adjusted Life Year (QALY). However, the degree to
      which generic measures can assess patients' specific experiences with their
      disease would remain unresolved. This has been neglected in the discussions on
      methods development and its impact on the QALY values obtained and resulting cost
      per QALY estimate underestimated. This study explored the content of utility
      instruments relevant to type 2 diabetes and Alzheimer's disease (AD) as examples,
      and the role of qualitative research in informing the trade-off between content
      coverage and consistency. METHOD: A literature review was performed to identify
      qualitative and quantitative studies regarding patients' experiences with type 2
      diabetes or AD, and associated treatments. Conceptual models for each indication
      were developed. Generic- and disease-specific instruments were mapped to the
      conceptual models. RESULTS: Findings showed that published descriptions of
      relevant concepts important to patients with type 2 diabetes or AD are available
      for consideration in deciding on the most comprehensive approach to utility
      assessment. While the 15-dimensional health related quality of life measure (15D)
      seemed the most comprehensive measure for both diseases, the Health Utilities
      Index 3 (HUI 3) seemed to have the least coverage for type 2 diabetes and the
      EuroQol-5 Dimensions (EQ-5D) for AD. Furthermore, some of the utility instruments
      contained items that could not be mapped onto either of the proposed conceptual
      models. CONCLUSIONS: Content of the utility measure has a significant impact on
      the treatment effects that can be observed. This varies from one disease to the
      next and as such contributes to lack of consistency in observable utility effects
      and incremental utility scores. This observation appears to have been omitted
      from the method development considerations such as reference methods. As a
      result, we recommend that patients' perspectives obtained via qualitative methods
      are taken into consideration in the ongoing methods development in health state
      descriptions for generic utility instruments. Also, as a more immediate
      contribution to improving decision making, we propose that a content map of the
      chosen utility measure with patient-reported domains be provided as standard
      reporting in utility measurement in order to improve the transparency of the
      trade-offs in relation to patient relevance and consistency.

PMID- 20152042
TI  - Efficacy of a progressive walking program and glucosamine sulphate
      supplementation on osteoarthritic symptoms of the hip and knee: a feasibility
      trial.
AB  - INTRODUCTION: Management of osteoarthritis (OA) includes the use of non
      pharmacological and pharmacological therapies. Although walking is commonly
      recommended for reducing pain and increasing physical function in people with OA,
      glucosamine sulphate has also been used to alleviate pain and slow the
      progression of OA. This study evaluated the effects of a progressive walking
      program and glucosamine sulphate intake on OA symptoms and physical activity
      participation in people with mild to moderate hip or knee OA. METHODS: Thirty-six
      low active participants (aged 42 to 73 years) were provided with 1500 mg
      glucosamine sulphate per day for 6 weeks, after which they began a 12-week
      progressive walking program, while continuing to take glucosamine. They were
      randomized to walk 3 or 5 days per week and given a pedometer to monitor step
      counts. For both groups, step level of walking was gradually increased to 3000
      steps/day during the first 6 weeks of walking, and to 6000 steps/day for the next
      6 weeks. Primary outcomes included physical activity levels, physical function
      (self-paced step test), and the WOMAC Osteoarthritis Index for pain, stiffness
      and physical function. Assessments were conducted at baseline and at 6-, 12-, 18
      , and 24-week follow-ups. The Mann Whitney Test was used to examine differences
      in outcome measures between groups at each assessment, and the Wilcoxon Signed
      Ranks Test was used to examine differences in outcome measures between
      assessments. RESULTS: During the first 6 weeks of the study (glucosamine
      supplementation only), physical activity levels, physical function, and total
      WOMAC scores improved (P < 0.05). Between the start of the walking program (Week
      6) and the final follow-up (Week 24), further improvements were seen in these
      outcomes (P < 0.05) although most improvements were seen between Weeks 6 and 12.
      No significant differences were found between walking groups. CONCLUSIONS: In
      people with hip or knee OA, walking a minimum of 3000 steps (approximately 30
      minutes), at least 3 days/week, in combination with glucosamine sulphate, may
      reduce OA symptoms. A more robust study with a larger sample is needed to support
      these preliminary findings. TRIAL REGISTRATION: Australian Clinical Trials
      Registry ACTRN012607000159459.

PMID- 20152044
TI  - Smart density: A more accurate method of measuring rural residential density for
      health-related research.
AB  - BACKGROUND: Studies involving the built environment have typically relied on US
      Census data to measure residential density. However, census geographic units are
      often unsuited to health-related research, especially in rural areas where
      development is clustered and discontinuous. OBJECTIVE: We evaluated the accuracy
      of both standard census methods and alternative GIS-based methods to measure
      rural density. METHODS: We compared residential density (units/acre) in 335
      Vermont school neighborhoods using conventional census geographic units (tract,
      block group and block) with two GIS buffer measures: a 1-kilometer (km) circle
      around the school and a 1-km circle intersected with a 100-meter (m) road-network
      buffer. The accuracy of each method was validated against the actual residential
      density for each neighborhood based on the Vermont e911 database, which provides
      an exact geo-location for all residential structures in the state. RESULTS:
      Standard census measures underestimate residential density in rural areas. In
      addition, the degree of error is inconsistent so even the relative rank of
      neighborhood densities varies across census measures. Census measures explain
      only 61% to 66% of the variation in actual residential density. In contrast, GIS
      buffer measures explain approximately 90% of the variation. Combining a 1-km
      circle with a road-network buffer provides the closest approximation of actual
      residential density. CONCLUSION: Residential density based on census units can
      mask clusters of development in rural areas and distort associations between
      residential density and health-related behaviors and outcomes. GIS-defined
      buffers, including a 1-km circle and a road-network buffer, can be used in
      conjunction with census data to obtain a more accurate measure of residential
      density.

PMID- 20152043
TI  - Cellular processes of v-Src transformation revealed by gene profiling of primary
      cells--implications for human cancer.
AB  - BACKGROUND: Cell transformation by the Src tyrosine kinase is characterized by
      extensive changes in gene expression. In this study, we took advantage of several
      strains of the Rous sarcoma virus (RSV) to characterize the patterns of v-Src
      dependent gene expression in two different primary cell types, namely chicken
      embryo fibroblasts (CEF) and chicken neuroretinal (CNR) cells. We identified a
      common set of v-Src regulated genes and assessed if their expression is
      associated with disease-free survival using several independent human tumor data
      sets. METHODS: CEF and CNR cells were infected with transforming, non
      transforming, and temperature sensitive mutants of RSV to identify the patterns
      of gene expression in response to v-Src-transformation. Microarray analysis was
      used to measure changes in gene expression and to define a common set of v-Src
      regulated genes (CSR genes) in CEF and CNR cells. A clustering enrichment regime
      using the CSR genes and two independent breast tumor data-sets was used to
      identify a 42-gene aggressive tumor gene signature. The aggressive gene signature
      was tested for its prognostic value by conducting survival analyses on six
      additional tumor data sets. RESULTS: The analysis of CEF and CNR cells revealed
      that cell transformation by v-Src alters the expression of 6% of the protein
      coding genes of the genome. A common set of 175 v-Src regulated genes (CSR genes)
      was regulated in both CEF and CNR cells. Within the CSR gene set, a group of 42 v
      Src inducible genes was associated with reduced disease- and metastasis-free
      survival in several independent patient cohorts with breast or lung cancer. Gene
      classes represented within this group include DNA replication, cell cycle, the
      DNA damage and stress responses, and blood vessel morphogenesis. CONCLUSION: By
      studying the v-Src-dependent changes in gene expression in two types of primary
      cells, we identified a set of 42 inducible genes associated with poor prognosis
      in breast and lung cancer. The identification of these genes provides a set of
      biomarkers of aggressive tumor behavior and a framework for the study of cancer
      cells characterized by elevated Src kinase activity.

PMID- 20152047
TI  - Construction of an Yucatec Maya soil classification and comparison with the WRB
      framework.
AB  - BACKGROUND: Mayas living in southeast Mexico have used soils for millennia and
      provide thus a good example for understanding soil-culture relationships and for
      exploring the ways indigenous people name and classify the soils of their
      territory. This paper shows an attempt to organize the Maya soil knowledge into a
      soil classification scheme and compares the latter with the World Reference Base
      for Soil Resources (WRB). METHODS: Several participative soil surveys were
      carried out in the period 2000-2009 with the help of bilingual Maya-Spanish
      speaking farmers. A multilingual soil database was built with 315 soil profile
      descriptions. RESULTS: On the basis of the diagnostic soil properties and the
      soil nomenclature used by Maya farmers, a soil classification scheme with a
      hierarchic, dichotomous and open structure was constructed, organized in groups
      and qualifiers in a fashion similar to that of the WRB system. Maya soil
      properties were used at the same categorical levels as similar diagnostic
      properties are used in the WRB system. CONCLUSIONS: The Maya soil classification
      (MSC) is a natural system based on key properties, such as relief position, rock
      types, size and quantity of stones, color of topsoil and subsoil, depth, water
      dynamics, and plant-supporting processes. The MSC addresses the soil properties
      of surficial and subsurficial horizons, and uses plant communities as qualifier
      in some cases. The MSC is more accurate than the WRB for classifying Leptosols.

PMID- 20152045
TI  - Personalized medicine in psoriasis: developing a genomic classifier to predict
      histological response to Alefacept.
AB  - BACKGROUND: Alefacept treatment is highly effective in a select group patients
      with moderate-to-severe psoriasis, and is an ideal candidate to develop systems
      to predict who will respond to therapy. A clinical trial of 22 patients with
      moderate to severe psoriasis treated with alefacept was conducted in 2002-2003,
      as a mechanism of action study. Patients were classified as responders or non
      responders to alefacept based on histological criteria. Results of the original
      mechanism of action study have been published. Peripheral blood was collected at
      the start of this clinical trial, and a prior analysis demonstrated that gene
      expression in PBMCs differed between responders and non-responders, however, the
      analysis performed could not be used to predict response. METHODS: Microarray
      data from PBMCs of 16 of these patients was analyzed to generate a treatment
      response classifier. We used a discriminant analysis method that performs sample
      classification from gene expression data, via "nearest shrunken centroid method".
      Centroids are the average gene expression for each gene in each class divided by
      the within-class standard deviation for that gene. RESULTS: A disease response
      classifier using 23 genes was created to accurately predict response to alefacept
      (12.3% error rate). While the genes in this classifier should be considered as a
      group, some of the individual genes are of great interest, for example, cAMP
      response element modulator (CREM), v-MAF avian musculoaponeurotic fibrosarcoma
      oncogene family (MAFF), chloride intracellular channel protein 1 (CLIC1, also
      called NCC27), NLR family, pyrin domain-containing 1 (NLRP1), and CCL5
      (chemokine, cc motif, ligand 5, also called regulated upon activation, normally T
      expressed, and presumably secreted/RANTES). CONCLUSIONS: Although this study is
      small, and based on analysis of existing microarray data, we demonstrate that a
      treatment response classifier for alefacept can be created using gene expression
      of PBMCs in psoriasis. This preliminary study may provide a useful tool to
      predict response of psoriatic patients to alefacept.

PMID- 20152046
TI  - Detection of anatid herpesvirus 1 gC gene by TaqMan fluorescent quantitative real
      time PCR with specific primers and probe.
AB  - BACKGROUND: Anatid herpesvirus 1 (AHV-1) is known for the difficulty of
      monitoring and controlling, because it has a long period of asymptomatic carrier
      state in waterfowls. Furthermore, as a significant essential agent for viral
      attachment, release, stability and virulence, gC (UL44) gene and its protein
      product (glycoprotein C) may play a key role in the epidemiological screening.
      The objectives of this study were to rapidly, sensitively, quantitatively detect
      gC gene of AHV-1 and provide the underlying basis for further investigating
      pcDNA3.1-gC DNA vaccine in infected ducks by TaqMan fluorescent quantitative real
      time PCR assay (FQ-PCR) with pcDNA3.1-gC plasmid. RESULTS: The repeatable and
      reproducible quantitative assay was established by the standard curve with a wide
      dynamic range (eight logarithmic units of concentration) and very good
      correlation values (1.000). This protocol was able to detect as little as 1.0 x
      101 DNA copies per reaction and it was highly specific to AHV-1. The TaqMan FQ
      PCR assay successfully detected the gC gene in tissue samples from pcDNA3.1-gC
      and AHV-1 attenuated vaccine (AHV-1 Cha) strain inoculated ducks respectively.
      CONCLUSIONS: The assay offers an attractive method for the detection of AHV-1,
      the investigation of distribution pattern of AHV-1 in vivo and molecular
      epidemiological screening. Meanwhile, this method could expedite related AHV-1
      and gC DNA vaccine research.

PMID- 20152048
TI  - SPRIT: Identifying horizontal gene transfer in rooted phylogenetic trees.
AB  - BACKGROUND: Phylogenetic trees based on sequences from a set of taxa can be
      incongruent due to horizontal gene transfer (HGT). By identifying the HGT events,
      we can reconcile the gene trees and derive a taxon tree that adequately
      represents the species' evolutionary history. One HGT can be represented by a
      rooted Subtree Prune and Regraft (RSPR) operation and the number of RSPRs
      separating two trees corresponds to the minimum number of HGT events. Identifying
      the minimum number of RSPRs separating two trees is NP-hard, but the problem can
      be reduced to fixed parameter tractable. A number of heuristic and two exact
      approaches to identifying the minimum number of RSPRs have been proposed. This is
      the first implementation delivering an exact solution as well as the intermediate
      trees connecting the input trees. RESULTS: We present the SPR Identification Tool
      (SPRIT), a novel algorithm that solves the fixed parameter tractable minimum RSPR
      problem and its GPL licensed Java implementation. The algorithm can be used in
      two ways, exhaustive search that guarantees the minimum RSPR distance and a
      heuristic approach that guarantees finding a solution, but not necessarily the
      minimum one. We benchmarked SPRIT against other software in two different
      settings, small to medium sized trees i.e. five to one hundred taxa and large
      trees i.e. thousands of taxa. In the small to medium tree size setting with
      random artificial incongruence, SPRIT's heuristic mode outperforms the other
      software by always delivering a solution with a low overestimation of the RSPR
      distance. In the large tree setting SPRIT compares well to the alternatives when
      benchmarked on finding a minimum solution within a reasonable time. SPRIT
      presents both the minimum RSPR distance and the intermediate trees. CONCLUSIONS:
      When used in exhaustive search mode, SPRIT identifies the minimum number of RSPRs
      needed to reconcile two incongruent rooted trees. SPRIT also performs quick
      approximations of the minimum RSPR distance, which are comparable to, and often
      better than, purely heuristic solutions. Put together, SPRIT is an excellent tool
      for identification of HGT events and pinpointing which taxa have been involved in
      HGT.

PMID- 20152049
TI  - Quantitative evaluation of motor function before and after engraftment of
      dopaminergic neurons in a rat model of Parkinson's disease.
AB  - Although gait change is considered a useful indicator of severity in animal
      models of Parkinson's disease, systematic and extensive gait analysis in animal
      models of neurological deficits is not well established. The CatWalk-assisted
      automated gait analysis system provides a comprehensive way to assess a number of
      dynamic and static gait parameters simultaneously. In this study, we used the
      Catwalk system to investigate changes in gait parameters in adult rats with
      unilateral 6-OHDA-induced lesions and the rescue effect of dopaminergic neuron
      transplantation on gait function. Four weeks after 6-OHDA injection, the
      intensity and maximal area of contact were significantly decreased in the
      affected paws and the swing speed significantly decreased in all four paws. The
      relative distance between the hind paws also increased, suggesting that animals
      with unilateral 6-OHDA-induced lesions required all four paws to compensate for
      loss of balance function. At 8 weeks post-transplantation, engrafted dopaminergic
      neurons expressed tyrosine hydroxylase. In addition, the intensity, contact area,
      and swing speed of the four limbs increased and the distance between the hind
      paws decreased. Partial recovery of methamphetamine-induced rotational response
      was also noted.

PMID- 20152050
TI  - Kinin B1 receptors contributes to acute pain following minor surgery in humans.
AB  - BACKGROUND: Kinins play an important role in regulation of pain and hyperalgesia
      after tissue injury and inflammation by activating two types of G-protein-coupled
      receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2
      receptor is constitutively expressed, whereas the B1 receptor is induced in
      response to inflammation. However, little is known about the regulatory effects
      of kinin receptors on the onset of acute inflammation and inflammatory pain in
      humans. The present study investigated the changes in gene expression of kinin
      receptors and the levels of their endogenous ligands at an early time point
      following tissue injury and their relation to clinical pain, as well as the
      effect of COX-inhibition on their expression levels. RESULTS: Tissue injury
      resulted in a significant up-regulation in the gene expression of B1 and B2
      receptors at 3 hours post-surgery, the onset of acute inflammatory pain.
      Interestingly, the up-regulation in the gene expression of B1 and B2 receptors
      was positively correlated to pain intensity only after ketorolac treatment,
      signifying an interaction between prostaglandins and kinins in the inflammatory
      pain process. Further, the gene expression of both B1 and B2 receptors were
      correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were
      significantly lower at the third hour compared to the first 2 hours in both the
      placebo and the ketorolac treatment groups but did not differ significantly
      between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene
      expression at 3 hours post-surgery with no significant effect by ketorolac
      treatment. Interestingly, the change in gene expression of TRPV1 was correlated
      to the change in gene expression of B1 receptor but not B2 receptor. CONCLUSIONS:
      These results provide evidence at the transcriptional level in a clinical model
      of tissue injury that up-regulation of kinin receptors are involved in the
      development of the early phase of inflammation and inflammatory pain. The up
      regulation of B1 receptors may contribute to acute inflammatory pain through
      TRPV1 activation.

PMID- 20152051
TI  - "Idiopathic" mental retardation and new chromosomal abnormalities.
AB  - Mental retardation is a heterogeneous condition, affecting 1-3% of general
      population. In the last few years, several emerging clinical entities have been
      described, due to the advent of newest genetic techniques, such as array
      Comparative Genomic Hybridization. The detection of cryptic
      microdeletion/microduplication abnormalities has allowed genotype-phenotype
      correlations, delineating recognizable syndromic conditions that are herein
      reviewed. With the aim to provide to Paediatricians a combined clinical and
      genetic approach to the child with cognitive impairment, a practical diagnostic
      algorithm is also illustrated. The use of microarray platforms has further
      reduced the percentage of "idiopathic" forms of mental retardation, previously
      accounted for about half of total cases. We discussed the putative pathways at
      the basis of remaining "pure idiopathic" forms of mental retardation,
      highlighting possible environmental and epigenetic mechanisms as causes of
      altered cognition.

PMID- 20152052
TI  - Management of an extrasphincteric fistula in an HIV-positive patient by using
      fibrin glue: a case report with tips and tricks.
AB  - BACKGROUND: Individuals with impaired immunity are at higher risk of perianal
      diseases. Concerning complex anal fistulas impaired healing and complication
      rates are also higher. Definitive treatment of a fistula aims controlling the
      purulent discharge and prevents its recurrence. It depends mainly on the
      trajectory of the fistula and the underlying disease. We present a case of a HIV
      positive patient with a complex extrasphincteric anal fistula who was treated
      successfully with fibrin glue application. We further, discuss tips and tricks
      when applying fibrin glue as plugging material in complex anal fistulas. CASE
      PRESENTATION: A sixty-one-year-old HIV-positive male referred to us for warts and
      extrasphincteric fistula. Because of the patients' immunological status, we opted
      against surgery and recommended fibrin glue plugging. The patient was discharged
      the same day. A follow-up examination was performed 5 days after the initial
      fibrin glue application showing that the fistula canal was obstructed. Three
      months and a year post-intervention the fistula tract remains closed. CONCLUSION:
      The best treatment for a disease gives at least the same result with the other
      treatments with minimised risk for the life of the patient and minimal
      application effort. Conservative closure of fistula with fibrin plugging is
      simple, safe and with less morbidity than surgery. Our patient was successfully
      treated without endangering his life despite his precarious medical state. Not
      everybody believes in the effectiveness of fibrin glue application, however we
      consider this solution in cases of complex fistulas at least as primary procedure
      in special populations such as the immunosupressed.

PMID- 20152053
TI  - Protein engineering of conger eel galectins by tracing of molecular evolution
      using probable ancestral mutants.
AB  - BACKGROUND: Conger eel galectins, congerin I (ConI) and congerin II (ConII), show
      the different molecular characteristics resulting from accelerating evolution. We
      recently reconstructed a probable ancestral form of congerins, Con-anc. It showed
      properties similar to those of ConII in terms of thermostability and carbohydrate
      recognition specificity, although it shares a higher sequence similarity with
      ConI than ConII. RESULTS: In this study, we have focused on the different amino
      acid residues between Con-anc and ConI, and have performed the protein
      engineering of Con-anc through site-directed mutagenesis, followed by the
      molecular evolution analysis of the mutants. This approach revealed the
      functional importance of loop structures of congerins: (1) N- and C-terminal and
      loop 5 regions that are involved in conferring a high thermostability to ConI;
      (2) loops 3, 5, and 6 that are responsible for stronger binding of ConI to most
      sugars; and (3) loops 5 and 6, and Thr38 residue in loop 3 contribute the
      specificity of ConI toward lacto-N-fucopentaose-containing sugars. CONCLUSIONS:
      Thus, this methodology, with tracing of the molecular evolution using ancestral
      mutants, is a powerful tool for the analysis of not only the molecular
      evolutionary process, but also the structural elements of a protein responsible
      for its various functions.

PMID- 20152054
TI  - Cerebral FDG-PET scanning abnormalities in optimally treated HIV patients.
AB  - BACKGROUND: The long-term neurological consequences of HIV infection and
      treatment are not yet completely understood. In this study we examined the
      prevalence of cerebral metabolic abnormalities among a cohort of neurologically
      intact HIV patients with fully suppressed HIV viral loads. Concomitant analyses
      of circulating brain derived neurotrophic factor (BDNF) were performed to
      correlate these abnormalities with potential signs of neuro
      regenerating/protective activity, and concomitant analyses of circulating tumour
      necrosis factor (TNF) alpha, interleukin (IL) 6, and soluble urokinase
      plasminogen activator receptor (suPAR) were performed to correlate these
      abnormalities with potential signs of neurodegenerative processes. METHODS: The
      study population consisted of HIV-positive patients known to be infected for more
      than 5 years and on antiretroviral (ARV) treatment for a minimum of three years
      with no history of virological failure, a CD4 count above 200 x 106 cells/l and
      no other co-morbidities. The distribution of the regional cerebral metabolic rate
      of glucose metabolism was measured using fluorine-18-flourodeoxyglucose positron
      emission tomography (FDG-PET) scanning. The PET scans were evaluated for
      individual pathology using Neurostat software and for group pathology using
      statistical parametric mapping (SPM). Circulating levels of BDNF, TNF alpha, IL-6
      and suPAR were measured by ELISA techniques. RESULTS: More than half (55%) of the
      patients exhibited varying severities of mesial frontal reduction in the relative
      metabolic rate of glucose. Compared to healthy subjects, the patients with
      abnormal FDG-PET scanning results had a shorter history of known HIV infection,
      fewer years on antiretroviral therapy and higher levels of circulating TNF alpha
      and IL-6 (p = 0.08). CONCLUSION: A large proportion of optimally treated HIV
      patients exhibit cerebral FDG-PET scanning abnormalities and elevated TNF alpha
      and IL-6 levels, which may indicate imminent neuronal damage. The neuroprotective
      effect of early ARV treatment should be considered in future prospective follow
      up studies.

PMID- 20152055
TI  - Drivers and barriers to acceptance of human-papillomavirus vaccination among
      young women: a qualitative and quantitative study.
AB  - BACKGROUND: Human papillomavirus (HPV) is a necessary cause of cervical dysplasia
      and cancer, and of genital warts. Few studies have examined attitudes to HPV
      vaccination since the introduction of HPV vaccines. We aimed to investigate the
      reasons for young women's acceptance or rejection of the quadrivalent HPV vaccine
      after its general availability in Denmark. METHOD: A literature review assessed
      attitudes towards HPV vaccination and the information was used to identify
      relevant questions for telephone and focus group interviews with women aged 16-26
      who had decided to receive or reject HPV vaccination. 435 women across Denmark
      were interviewed by telephone. Qualitative interviews were undertaken in focus
      groups with 33 women living in Odense who had completed the telephone survey.
      Four focus groups were set up according to age (16-20 and 21-26 years of age) and
      acceptance/rejection of the vaccine. RESULTS: Of 839 women initially contacted by
      telephone, 794 were included, 411 (49%) said they accepted vaccination but only
      201 (24%) had actually received the vaccine and these latter were interviewed.
      242 women said they refused vaccination of which 234 were interviewed. Women who
      were undecided were excluded from the study. Prevention of cervical cancer was
      the main driver for acceptance of the vaccine, followed by parental encouragement
      and financial support, personal experience of someone with cancer and
      recommendation by health-care professionals. The greatest barrier to vaccination
      was its cost. A lack of information about the benefits of vaccination for
      sexually active women was also an important barrier and the older participants in
      particular considered that they were too old to be vaccinated. Knowledge about
      HPV and its role in the development of cervical cancer and genital warts was
      poor. CONCLUSIONS: The difference between intention to be vaccinated and starting
      vaccination was considerable, and a large proportion of women aged 16-26 did not
      wish to be vaccinated. If the most important barriers to vaccination were
      addressed (cost and a lack of information about vaccination benefits), it is
      likely that the uptake of vaccination in Denmark would increase substantially.

PMID- 20152056
TI  - Contingency planning for a deliberate release of smallpox in Great Britain--the
      role of geographical scale and contact structure.
AB  - BACKGROUND: In the event of a release of a pathogen such as smallpox, which is
      human-to-human transmissible and has high associated mortality, a key question is
      how best to deploy containment and control strategies. Given the general
      uncertainty surrounding this issue, mathematical modelling has played an
      important role in informing the likely optimal response, in particular defining
      the conditions under which mass-vaccination would be appropriate. In this paper,
      we consider two key questions currently unanswered in the literature: firstly,
      what is the optimal spatial scale for intervention; and secondly, how sensitive
      are results to the modelling assumptions made about the pattern of human
      contacts? METHODS: Here we develop a novel mathematical model for smallpox that
      incorporates both information on individual contact structure (which is important
      if the effects of contact tracing are to be captured accurately) and large-scale
      patterns of movement across a range of spatial scales in Great Britain. RESULTS:
      Analysis of this model confirms previous work suggesting that a locally targeted
      'ring' vaccination strategy is optimal, and that this conclusion is actually
      quite robust for different socio-demographic and epidemiological assumptions.
      CONCLUSIONS: Our method allows for intuitive understanding of the reasons why
      national mass vaccination is typically predicted to be suboptimal. As such, we
      present a general framework for fast calculation of expected outcomes during the
      attempted control of diverse emerging infections; this is particularly important
      given that parameters would need to be interactively estimated and modelled in
      any release scenario.

PMID- 20152057
TI  - Inter-annual variation in prevalence and intensity of mite parasitism relates to
      appearance and expression of damselfly resistance.
AB  - BACKGROUND: Insects can resist parasites using the costly process of melanotic
      encapsulation. This form of physiological resistance has been studied under
      laboratory conditions, but the abiotic and biotic factors affecting resistance in
      natural insect populations are not well understood. Mite parasitism of
      damselflies was studied in a temperate damselfly population over seven seasons to
      determine if melanotic encapsulation of mite feeding tubes was related to degree
      of parasitism, host sex, host size, emergence timing, duration of the emergence
      period, and average daily air temperature. RESULTS: Although parasite prevalence
      in newly emerged damselflies was > 77% each year, hosts did not resist mites in
      the early years of study. Resistance began the year that there was a dramatic
      increase in the number of mites on newly emerged damselflies. Resistance
      continued to be correlated with mite prevalence and intensity throughout the
      seven-year study. However, the percentage of hosts resisting only ranged from 0
      13% among years and resistance was not sex-biased and was not correlated with
      host size. Resistance also was not correlated with air temperature or with timing
      or duration of damselfly emergence. CONCLUSIONS: Resistance in host damselflies
      was weakly and variably expressed over the study period. Factors such as
      temperature, which have been identified in laboratory studies as contributing to
      resistance by similar hosts, can be irrelevant in natural populations. This lack
      of temperature effect may be due to the narrow range in temperatures observed at
      host emergence among years. Degree of mite parasitism predicted both the
      appearance and continued expression of resistance among parasitized damselflies.

PMID- 20152058
TI  - An enhancer peptide for membrane-disrupting antimicrobial peptides.
AB  - BACKGROUND: NP4P is a synthetic peptide derived from a natural, non-antimicrobial
      peptide fragment (pro-region of nematode cecropin P4) by substitution of all
      acidic amino acid residues with amides (i.e., Glu --> Gln, and Asp --> Asn).
      RESULTS: In the presence of NP4P, some membrane-disrupting antimicrobial peptides
      (ASABF-alpha, polymyxin B, and nisin) killed microbes at lower concentration
      (e.g., 10 times lower minimum bactericidal concentration for ASABF-alpha against
      Staphylococcus aureus), whereas NP4P itself was not bactericidal and did not
      interfere with bacterial growth at <or= 300 microg/mL. In contrast, the
      activities of antimicrobial agents with a distinct mode of action (indolicidin,
      ampicillin, kanamycin, and enrofloxacin) were unaffected. Although the membrane
      disrupting activity of NP4P was slight or undetectable, ASABF-alpha permeabilized
      S. aureus membranes with enhanced efficacy in the presence of NP4P. CONCLUSIONS:
      NP4P selectively enhanced the bactericidal activities of membrane-disrupting
      antimicrobial peptides by increasing the efficacy of membrane disruption against
      the cytoplasmic membrane.

PMID- 20152060
TI  - Relative expression of the 14-3-3 gene in different morphotypes of cysts of
      Echinococcus granulosus isolated from the Indian buffalo.
AB  - The metacestode stage of Echinococcus granulosus is of zoonotic importance. In
      general, the 14-3-3 protein is involved in multiplication and survival of
      eukaryotes. Therefore, this communication presents succinct information on
      relative expression of the 14-3-3 protein in six different morphotypes of cysts
      of E. granulosus. All isolated E. granulosus belonged to the common sheep strain
      (G1). Relative expression of the 14-3-3 protein was higher in fertile cysts when
      compared to sterile cysts. The predicted amino acid sequence of the 14-3-3
      protein was closely clustered with zeta-type isoforms 1 and 2 of the 14-3-3
      protein. In addition, the present study demonstrates the presence of the 14-3-3
      protein which until now had not been detected in the germinal layer. Our findings
      indicate that the expression of this biomolecule in the germinal layer of sterile
      organisms may contribute to the development and survival of the parasite in the
      host. The uniform expression of actin II conclusively proves the survivability of
      the harvested organisms.

PMID- 20152059
TI  - Genetic polymorphisms of matrix metalloproteinases and their inhibitors in
      potentially malignant and malignant lesions of the head and neck.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that
      are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation
      of matrix is a key event in progression, invasion and metastasis of potentially
      malignant and malignant lesions of the head and neck. It might have an important
      polymorphic association at the promoter regions of several MMPs such as MMP-1 (
      1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2
      (-418 G/C or C/C). Tissue inhibitors of metalloproteinases (TIMPs) are naturally
      occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the
      breakdown of ECM. Currently, many MMP inhibitors (MMPIs) are under development
      for treating different malignancies. Useful markers associated with molecular
      aggressiveness might have a role in prognostication of malignancies and to better
      recognize patient groups that need more antagonistic treatment options.
      Furthermore, the introduction of novel prognostic markers may also promote
      exclusively new treatment possibilities, and there is an obvious need to identify
      markers that could be used as selection criteria for novel therapies. The
      objective of this review is to discuss the molecular functions and polymorphic
      association of MMPs and TIMPs and the possible therapeutic aspects of these
      proteinases in potentially malignant and malignant head and neck lesions. So far,
      no promising drug target therapy has been developed for MMPs in the lesions of
      this region. In conclusion, further research is required for the development of
      their potential diagnostic and therapeutic possibilities.

PMID- 20152061
TI  - Applying predator-prey theory to modelling immune-mediated, within-host
      interspecific parasite interactions.
AB  - Predator-prey models are often applied to the interactions between host immunity
      and parasite growth. A key component of these models is the immune system's
      functional response, the relationship between immune activity and parasite load.
      Typically, models assume a simple, linear functional response. However, based on
      the mechanistic interactions between parasites and immunity we argue that
      alternative forms are more likely, resulting in very different predictions,
      ranging from parasite exclusion to chronic infection. By extending this framework
      to consider multiple infections we show that combinations of parasites eliciting
      different functional responses greatly affect community stability. Indeed, some
      parasites may stabilize other species that would be unstable if infecting alone.
      Therefore hosts' immune systems may have adapted to tolerate certain parasites,
      rather than clear them and risk erratic parasite dynamics. We urge for more
      detailed empirical information relating immune activity to parasite load to
      enable better predictions of the dynamic consequences of immune-mediated
      interspecific interactions within parasite communities.

PMID- 20152062
TI  - Selection of Apis mellifera workers by the parasitic mite Varroa destructor using
      host cuticular hydrocarbons.
AB  - The parasitic mite, Varroa destructor, is the most important threat for
      apiculture in most bee-keeping areas of the world. The mite is carried to the bee
      brood cell, where it reproduces, by a nurse bee; therefore the selection of the
      bee stage by the parasite could influence its reproductive success. This study
      investigates the role of the cuticular hydrocarbons of the European honeybee
      (Apis mellifera) in host-selection by the mite. Preliminary laboratory bioassays
      confirmed the preference of the varroa mite for nurse bees over pollen foragers.
      GC-MS analysis of nurse and pollen bees revealed differences in the cuticular
      hydrocarbons of the two stages; in particular, it appeared that pollen bees have
      more (Z)-8-heptadecene than nurse bees. Laboratory experiments showed that
      treatment of nurse bees with 100 ng of the pure compound makes them repellent to
      the varroa mite. These results suggest that the mite can exploit the differences
      in the cuticular composition of its host for a refined selection that allows it
      to reach a brood cell and start reproduction. The biological activity of the
      alkene encourages further investigations for the development of novel control
      techniques based on this compound.

PMID- 20152063
TI  - Iron metabolism in trypanosomatids, and its crucial role in infection.
AB  - Iron is almost ubiquitous in living organisms due to the utility of its redox
      chemistry. It is also dangerous as it can catalyse the formation of reactive free
      radicals - a classical double-edged sword. In this review, we examine the uptake
      and usage of iron by trypanosomatids and discuss how modulation of host iron
      metabolism plays an important role in the protective response. Trypanosomatids
      require iron for crucial processes including DNA replication, antioxidant
      defence, mitochondrial respiration, synthesis of the modified base J and, in
      African trypanosomes, the alternative oxidase. The source of iron varies between
      species. Bloodstream-form African trypanosomes acquire iron from their host by
      uptake of transferrin, and Leishmania amazonensis expresses a ZIP family cation
      transporter in the plasma membrane. In other trypanosomatids, iron uptake has
      been poorly characterized. Iron-withholding responses by the host can be a major
      determinant of disease outcome. Their role in trypanosomatid infections is
      becoming apparent. For example, the cytosolic sequestration properties of NRAMP1,
      confer resistance against leishmaniasis. Conversely, cytoplasmic sequestration of
      iron may be favourable rather than detrimental to Trypanosoma cruzi. The central
      role of iron in both parasite metabolism and the host response is attracting
      interest as a possible point of therapeutic intervention.

PMID- 20152064
TI  - The impact of symptomatic hoarding in OCD and its treatment.
AB  - BACKGROUND: The value of defining subtypes in obsessive compulsive disorder (OCD)
      has become an important issue for recent debate. Probably the most robust example
      of subtyping is the identification of hoarding as being different both in terms
      of psychopathology and response to treatment. AIMS: To identify differences in
      psychopathology and treatment response in OCD patients with and without
      additional hoarding symptoms. METHOD: Patients who had undertaken CBT for OCD
      were selected as falling into either a high or a low hoarding group. The high
      hoarding group (n = 18) was selected on the basis of a high score on the hoarding
      subscale of a self-report measure of OCD symptoms in addition to reaching
      clinician judged "threshold" on the hoarding item of the Obsessive Compulsive
      Personality Disorder (OCPD) SCID-II module. The low hoarding group (n = 20) was
      selected on the basis of a low score on the hoarding subscale and a clinician
      judgement that the hoarding item of the OCPD SCID-II module was "absent".
      RESULTS: On some measures of pre-treatment psychopathology, patients with OCD
      with hoarding symptoms were more severely affected than those without hoarding
      symptoms. It was found that there was no difference in eventual treatment outcome
      between the two groups, although there was some evidence that the hoarding group
      showed greater symptom decreases. CONCLUSIONS: The presence of hoarding symptoms
      does not negatively impact on the treatment of OCD.

PMID- 20152065
TI  - Effectiveness of group and individual formats of a combined motivational
      interviewing and cognitive behavioral treatment program for problem gambling: a
      randomized controlled trial.
AB  - BACKGROUND: The study aimed to assess the effectiveness of group and individual
      formats of a combined motivational interviewing and cognitive behavioral
      treatment (CBT) program for problem gamblers (PGs) using a randomized controlled
      design. METHOD: One hundred and two PGs were randomly assigned to individual or
      group CBT conditions. Twenty-eight of these participants were randomly allocated
      to a 6-week waitlist control condition prior to receiving the designated
      treatment. RESULTS: At post-treatment, there were significant improvements in all
      dependent variables (frequency and amount gambled, gambling urges, gambling
      cognitions, negative psychological states, and life satisfaction) for both the
      treatment conditions but not for the waitlist condition. Individuals that
      completed the individual (compared to group) treatment condition generally had
      higher effect sizes for gambling correlates. Therapeutic gains for gambling
      correlates were generally maintained at 6-month follow-up. CONCLUSIONS: A
      combined motivational interviewing and CBT program applied in group or individual
      format can improve PG behaviors, as well as gambling correlates.

PMID- 20152067
TI  - Epigenetic mechanisms regulating normal and malignant haematopoiesis: new
      therapeutic targets for clinical medicine.
AB  - It is now well established that epigenetic phenomena and aberrant gene regulation
      play a major role in carcinogenesis. These include aberrant gene silencing by
      imposing inactive histone marks on promoters, aberrant methylation of DNA at CpG
      islands, and the active repression of promoters by oncoproteins. In addition,
      many malignant cells also show aberrant gene activation due to constitutively
      active signalling. The next frontier in cancer research will be to examine how,
      at the molecular level, small mutations that alter the regulatory phenotype of a
      cell give rise after a number of cell divisions to the vast deregulation
      phenomena seen in malignant cells. This review outlines recent insights into how
      normal cell differentiation in the haematopoietic system is subverted in
      leukaemia and it introduces the molecular players involved in this process. It
      also summarises the results of recent clinical trials trying to reverse aberrant
      epigenetic regulation by employing agents influencing global epigenetic
      regulators.

PMID- 20152069
TI  - The nose and paranasal sinuses.
AB  - The airways should be considered as a functional unit. Indeed, disorders
      involving the upper respiratory tract (URT) spread to the lower respiratory tract
      (LRT). Modern functional anatomy divides URT in three, mutually dependent,
      junction boxes: i) the ostio-meatal complex (OMC), ii) the spheno-ethmoidal
      recess (SER), and iii) the rhinopharynx (RP). The first is the most interesting
      as it joins the anterior paranasal sinuses with the nose. The correct ventilation
      and the effective mucociliary clearance of these three pathophysiologic junction
      boxes condition the healthy physiology of the entire respiratory system. The OMC,
      SER and RP obstruction is the first pathogenic step in the inflammatory cascade
      of the rhino-sinusal-pharyngeal disorders. The inflammation of the respiratory
      mucosa is the main pathogenic factor for airway obstruction that may be
      generically defined as a heterogeneous group of pathologies. Moreover, the
      bacterial biofilms are an important local cause of recurrent diseases: they are a
      strategic modality of survival set up by bacteria and the main cause of their
      resistance to systemic antibiotic therapy.

PMID- 20152070
TI  - Functional anatomy of the Eustachian tube.
AB  - The Eustachian tube (ET) is divided in 3 portions: a bony portion, a
      cartilaginous portion, and a junctional portion. From an anatomical-functional
      point of view, the bony portion of ET is the region of ventilation and clearance
      of secretions, and is lined by pseudostratified, ciliated, columnar epithelium,
      with an anti-gravitational direction of the drainage. The ET in the bony portion
      is in a state of forced opening. The cartilaginous portion is instead the heart
      of this dynamic system tube, because the mechanism of opening and closing of the
      tube is at this level. ET is normally closed, and it opens only during
      swallowing, being essential for good functioning of the middle ear, because it
      provides ventilation from the nasopharynx to the middle ear, and, at the same
      time, clearance of secretions from the middle ear-mastoid unit to the
      nasopharynx. Moreover, the ET protects the middle ear against nasopharyngeal
      pressure variations, ascending secretions, and microorganisms. The ability to
      develop all these functions makes the tube a complex organ.

PMID- 20152071
TI  - The immunity of upper airways.
AB  - A specialized immune system, called the nasopharynx-associated lymphoid tissue
      (NALT), is located on the mucosal surface of upper airways and is composed of
      both innate and specific immunity elements, closely related to each other and to
      the systemic defence, and spread over the nasopharynx, the nose and the middle
      ear. The NALT has a major role as regards to the infectious diseases of this
      area, which are the most common in children. It is also an interesting field of
      experimentation for new vaccine strategies in the future.

PMID- 20152072
TI  - Risk factors for upper airway diseases.
AB  - Upper respiratory infection is the most common reason for seeking medical care
      for children. Recurrent viral respiratory infections and subsequent complications
      are a burden for children, their families and society. It has been estimated that
      at least 6 percent of children younger than 6 yr of age presents recurrent
      respiratory infections, as consequence of an increased exposure to infectious
      agents during the first years of life, when immune functions are still immature.
      Pediatricians must identify risk factors predisposing to upper respiratory tract
      infections and plan specific preventive strategies, ie avoidance of precocious
      day-care attendance and secondary smoke. Vaccination against influenza and
      pneumococcal diseases should always be recommended.

PMID- 20152073
TI  - The infections of the upper respiratory tract in children.
AB  - Upper respiratory tract infections in children are common and usually self
      limiting conditions, which include acute otitis media (AOM), acute rhinosinusitis
      (ARS), and acute pharyngitis (AP). Management of pediatric AOM considers
      observation strategy for selected and uncomplicated cases, older than 2 years of
      age, only when adequate follow-up can be ensured. Otherwise, an antibiotic
      treatment should be prescribed. Amoxicillin should be preferred as the first
      choice therapy. Switch therapy to ceftriaxone is suggested if amoxicillin regimen
      failure occurs within 48-72 hours. The diagnosis of ARS is established by the
      persistence of purulent nasal of post-nasal draining lasting at least 10 days
      especially if accompanied by supporting symptoms and signs. Amoxicillin is the
      first choice drug for mild ARS in children. When symptoms persist or worsen,
      amoxicillin/clavulanate or cefpodoxime proxetil, or ceftriaxone are recommended.
      Clinical criteria alone are not sufficiently accurate in children with AP to
      distinguish bacterial and viral etiology. Thus microbiological evaluation is
      needed and positive throat culture or rapid antigen detection test are required
      to establish the diagnosis of streptococcal pharyngitis and consequently to
      prescribe antibiotic treatment. The first choice treatment in European countries
      still remains amoxicillin or amoxicillin/clavulanate.

PMID- 20152074
TI  - Insights into infectious otitis media.
AB  - Otitis media is a multifactorial disease. It represents a major public health
      burden, as it is the most common diagnosis in children and is characterized by
      both immediate and long-term morbidity. For years the knowledge about risk
      factors and microbiology of otitis media has been relatively stable. In recent
      years new data have been gathered regarding different microbiological aspects of
      otitis media. This new knowledge may contribute toward the development and
      implementation of therapeutic and preventive strategies.

PMID- 20152075
TI  - The clinical spectrum of rhinosinusitis in children.
AB  - Rhinosinusitis is an extremely common disease that is often underreported,
      especially in children. Its clinical spectrum includes acute rhinosinusitis (ARS)
      which may present in the forms of ARS with persistent symptoms and ARS with
      severe symptoms and chronic rhinosinusitis (CRS), characterized by a duration
      longer than 12 weeks and prevalence of symptoms such as nasal congestion and
      cough. Moreover, rhinosinusitis may present with associated disorders, that are
      nasal polyposis and aspirin sensitivity, asthma, otitis media with effusion, and
      gastroesophageal reflux. A particular form is fungal rhinosinusitis, presenting
      in an invasive and noninvasive form, the latter including allergic fungal
      sinusitis, which is the most common form of fungal rhinosinusitis and should be
      suspected in children with nasal polyposis and atopy.

PMID- 20152076
TI  - Rhinosinusitis and asthma.
AB  - Chronic rhinosinusitis and asthma are not simply localized disease processes, but
      part of a systemic inflammatory disease affecting the respiratory tract. There is
      a correlation between severity of asthma and the clinical and imaging features of
      rhinosinusitis. It is very important to understand that in patients with chronic
      sinus disease, both upper and lower airways need to be evaluated and treated and
      that in patients with moderate or severe asthma, the sinus area should always be
      investigated, regardless of the presence or not of nasal symptoms. Nasal
      endoscopy may be considered a feasible and correct approach in asthmatic children
      to investigate rhinosinusal or adenoid infections, even if they do not present
      with any clinical sign. Thus, it becomes more and more important to perform a
      simple, easy and safe nasal endoscopy, in order to have a better chance to treat
      asthmatic children correctly by identifying a subclinical or an occult
      rhinosinusal infection.

PMID- 20152077
TI  - Upper respiratory tract infections and atopy.
AB  - Upper respiratory tract infections and allergic diseases are particularly common
      in children. It seems that atopy may predispose to more severe symptoms during
      infections and may facilitate together with other genetic factors and with
      adverse environmental conditions the occurrence of chronic rhinosinusitis (CRS)
      and chronic otitis media with effusion (OME). The initial event in CRS is the
      obstruction of the osteomeatal complex, while obstruction and dysfunction of the
      Eustachian tube may be the preliminary event for the development of OME.

PMID- 20152078
TI  - Rhinosinusitis and otitis media: the link with adenoids.
AB  - Rhinosinusitis and otitis media are very common diseases observed in pediatric
      patients. A clear association has been reported in literature between these two
      conditions. Even concordance in the microbiologic findings has been reported.
      These findings lead to a discussion in regard to a possible relationship between
      the two diseases and an eventual interference of another concomitant condition
      promoting this association. A key role in the linkage between rhinosinusitis and
      otitis media has been attributed to hypertrophic adenoidal tissue because of its
      mechanical obstruction of both choanae and Eustachian tube orifices. Recently
      some works in literature evidenced the presence of bacterial biofilms on adenoids
      and suggested a responsibility of bacterial biofilms in both chronic
      rhinosinusitis and otitis media. The debate is still active and more
      investigations are needed to clarify these topics.

PMID- 20152079
TI  - Diagnostic imaging of the pediatric nasal cavity and paranasal sinuses.
AB  - The vast majority of nasal and paranasal sinuses (PNS) diseases in childhood are
      of inflammatory origin. In particular, during the early rapid development of PNS
      rhinosinusitis are exceedingly frequent in both acute and chronic forms. However
      other diseases such as primarily congenital malformation, but also neoplasms can
      affect the nasal cavity (NC) and PNS during pediatric age. Modern radiological
      techniques such as multidetector computerized tomography (MDCT) or magnetic
      resonance imaging (MRI) are becoming of greater importance in the diagnosis of
      chronic or complicated inflammatory processes of NC and PNS and in the
      differential diagnosis with the other less frequent diseases. The characteristic
      features of MDCT and MRI and their diagnostic role in the more frequent pediatric
      inflammatory, neoplastic and congenital diseases of NC and PNS are reviewed.

PMID- 20152080
TI  - Role of nasal cytology.
AB  - Nasal cytology represents a valid method in the differential diagnosis of
      allergic and non-allergic nasal diseases, as it is simple, safe, non-invasive,
      cost-effective, and easy to perform both in the medical and paediatric office. In
      particular, through cytological investigation it is possible to diagnose a group
      of non-allergic infective rhinitis that still today constitutes a vague aspect of
      the clinical-diagnostic-therapeutic approach to eosinophilic non-allergic
      rhinitis (NARES), non-allergic rhinitis mast cell (NARMA), neutrophilic non
      allergic rhinitis (NARNA), and eosinophil-mast cell non-allergic rhinitis
      (NARESMA). Preventive treatment of nasal diseases, when guided by rhinocytograms,
      leads to a favorable clinical and time-dependent outcome. These advantages are
      reflected in a better quality of life and in a reduction in National Health
      Service costs, without chronic evolution of the disease to complications.

PMID- 20152081
TI  - Clinical application of nasal nitric oxide measurement.
AB  - Nitric oxide is present in high concentration in the upper respiratory tract. The
      main source of this gaseous molecule is the paranasal sinus epithelium. The
      physiological role of this mediator is to contribute to local host defense,
      modulate ciliary motility and serve as an aerocrine mediator in helping to
      maintain adequate ventilationperfusion matching in the lung. Abnormal values of
      nasal NO (nNO) have been reported in different pathological conditions of the
      respiratory tract. Reduced nNO values have been recorded in subjects with acute
      and chronic sinusitis, cystic fibrosis and nasal polyps. Particularly low
      concentrations have been described in children with primary ciliary dyskinesia,
      so nNO measurement has been proposed as a reliable screening test for this
      chronic lung disease.

PMID- 20152082
TI  - Rhinosinusitis management in pediatrics: an overview.
AB  - Rhinosinusitis is an inflammation of one or more paranasal sinuses, usually
      caused by an infection. The clinical appearance of rhinosinusitis may be
      heterogeneous and change with patient age, the duration of symptoms and, above
      all, the seriousness of the illness. The diagnosis of rhinosinusitis should only
      be based on anamnestic and clinical criteria in children with serious or
      persistent symptoms of upper respiratory tract infection, or which appear within
      a short time of an apparent recovery. Imaging studies are not usually necessary
      to confirm a diagnosis of uncomplicated acute bacterial rhinosinusitis. Paranasal
      sinus computed tomography or magnetic resonance and optical fibre rhinoscopy are
      required in severe cases that do not respond to antibiotic therapy. Antibiotics
      are recommended in cases of mild acute bacterial rhinosinusitis as a means of
      accelerating the resolution of symptoms, and they are mandatory in severe acute
      cases in order to cure the disease and avoid the possible onset of severe
      complications.

PMID- 20152083
TI  - Paediatric upper respiratory infections: the role of antibiotics.
AB  - To review current clinical evidence for the use of antibiotics in paediatric
      upper paediatric respiratory infections, repeated PubMed searches using the
      template algorithm -rhinosinusitis/otitis/ tonsillitis AND ()- with the settings:
      -Humans; English; All Child 0-18; Clinical trial; Review; Methanalysis;
      Guideline; Last 10 years- for the following comparators: antibiotic; amoxicillin;
      clavulanate; penicillin; cephalosporin; macrolide; erythromycin; rokitamycin;
      clindamycin; trimethoprim-sulfamethoxazole, cefopodoxime, cefdinir, cefuroxime,
      ceftriaxone. The authors clinical experience in the paediatric allergy unit of a
      University hospital was also drawn upon. A narrative review was drafted to update
      paediatricians on the topic. Many paediatric studies and guidelines were
      retrieved satisfying current evidence-based medicine standards. There are
      stringent indications for antibiotic use in URTIs. The paediatric use is
      widespread raising doubts on their appropriate prescription in many countries.
      Evidence for the efficacy of antibiotic treatment for paediatric URTIs is
      available and this treatment should be included in individualised patient
      protocols on the basis of the clinical literature. Caution must be posed at the
      local level taking in account epidemiologic and microbiologic data to avoid
      overprescription.

PMID- 20152084
TI  - Upper airways disease: role of corticosteroids.
AB  - Nasal topical steroids (INCSs) are well established effective therapy in allergic
      rhinitis both in children and adults. There is clear benefit in using INCSs over
      antihistamines in allergic rhinitis while short courses of oral corticosteroids
      (CSs) may be indicated in severe cases. The addition of INCSs to oral antibiotics
      has been proven to be more effective than antibiotics alone for achieving
      symptomatic improvement in patients with acute rhino sinusitis. INCSs as
      monotherapy are also effective in the treatment of allergic rhinosinusitis (ARS).
      Several randomized controlled trials have evaluated the role of INCSs in chronic
      RS with the majority demonstrating a beneficial effect. In adults, the clinical
      efficacy of oral corticosteroids in the management of chronic RS with nasal
      polyposis is well established. There are no randomized controlled trials
      evaluating the efficacy of systemic CSs in chronic RS without nasal polyposis.

PMID- 20152085
TI  - Targeting the nasal cavity in rhinitis and sinusitis.
AB  - Successful aerosol therapy depends mainly on targeting an adequate dose of drug
      to the appropriate receptors in the respiratory tract. Over the last years, major
      innovations have occurred in the delivery of inhaled drugs to the lungs. Despite
      the fact that more individuals suffer from rhinitis or sinusitis than from asthma
      or COPD, research into nasal delivery of aerosolized drugs remains scarce.
      Knowledge of the delivered dose, its regional distribution, and the manner in
      which drug targeting may be affected by nasal anatomy, air flow and disease
      condition is very important. Challenges to delivery of aerosolized medications to
      appropriate targets in the nasal cavity have been scarcely considered. A less
      than-optimal technique can result in decreased delivery, reduced efficacy,
      increased risk of side-effects and high drug wasting. Knowledge of the actual
      dose and the site of deposition of the delivered drug would permit precise
      assessment of the relative performance of the delivery systems employed for a
      specific drug. Optimal physical aerosol characteristics and patient delivery
      profiles need to be definitively researched for each inhaled drug. There is a
      strong need to develop new engineered drug inhalation devices well-matched with
      improved drug formulations for the treatment of rhinitis or sinusitis.

PMID- 20152086
TI  - Treatment of rhinosinusitis: other medical options.
AB  - Medical options other than antibiotics or corticosteroids for treating
      rhinosinusitis include non-specific treatments such as nasal decongestants, naso
      sinusal washings, antihistamines, antileukotrienes, mucolytic agents,
      immunomodulators and immunostimulants, as well as specific agents such as
      antimycotics in fungal sinusitis or antireflux agents in sinusitis associated to
      gastroesophageal reflux. In subjects with chronic sinusitis and/or nasal
      polyposis related to aspirin hypersensitivity protocols of desensitization are
      available. The available scientific evidence is good for naso-sinus washings with
      saline solutions, antihistamines in acute allergic rhinosinusitis,
      antileukotrienes in chronic sinusitis, bacterial lysates for prevention of
      recurrent sinusitis, and aspirin desensitisation in subjects with aspirin
      exacerbated respiratory disease with chronic sinusitis and nasal polyposis. The
      other treatment options are still in search of scientific demonstration.

PMID- 20152087
TI  - Treatment of rhinosinusitis: the role of surgery.
AB  - The treatment of rhinosinusitis in children is mostly medical. Surgery is
      indicated in few but important exceptions: orbital or intracranial complications
      of acute rhinosinusitis not responding to medical therapy, chronic rhinosinusitis
      (CRS) with persisting sinonasal infection and purulent discharge, cystic
      fibrosis, ciliary diskinesia, dacryocystitis due to sinusitis and resistant to
      medical treatment, fungal rhinosinusitis. According to recent data, 50 percent of
      ENT specialist perform an adenoidectomy to manage CRS before endoscopic sinus
      surgery (ESS). ESS techniques introduced in mid 90s, has significantly modified
      the treatment of complications of acute rhinosinusitis and of selected cases of
      chronic recurrent infections. ESS consists of minimally invasive surgical
      procedure as middle meatal antrostomy and anterior ethmoidectomy. Evidence
      suggests that adenoidectomy and ESS are the most frequent surgical procedure
      performed in RS management.

PMID- 20152088
TI  - A retrospective case note review of sex worker attendees at sexual health clinics
      in the western suburbs of Sydney.
AB  - BACKGROUND: Sex workers (SWs) are globally recognised to be at high risk for the
      acquisition and transmission of sexually transmissible infections (STIs). There
      is a paucity of published data concerning SWs from the western suburbs of Sydney,
      with the last published study conducted in 1988. Therefore, we conducted a study
      to determine the demographics, sexual practices and health care needs of SWs
      attending Sexual Health Clinics (SHCs) in the region. METHODS: Self-identified
      SWs presenting to SHCs in western Sydney between April 2007 and March 2008 were
      identified using clinic databases. A case note review was then undertaken.
      RESULTS: One hundred and eighty-five female SWs were included in the analysis.
      Ninety-eight (54.5%) were born overseas (predominantly China) and 82 (45.6%) were
      born in Australia. One hundred and seventeen (68%) were English speaking
      backgrounds (ESB), while 55 (32%) were from non-English speaking backgrounds
      (NESB). Seventy-two (38.9%) were symptomatic on attendance, with vaginal
      discharge the most common symptom. Chlamydia was the most commonly reported STI
      in the previous 12 months with 28 cases (15.1%). SWs from NESB were significantly
      more likely to be older, symptomatic, have a hepatitis B diagnosis in the
      previous year and work more shifts per week, compared with SWs from ESB. SWs born
      overseas were more likely to be symptomatic than Australian born SWs who, in
      turn, were more likely to have a hepatitis C diagnosis in the previous year.
      CONCLUSION: SWs from NESB would potentially benefit from evidenced-based,
      culturally and linguistically appropriate interventions and targeted health
      promotion.

PMID- 20152089
TI  - HIV result giving. Is it time to change our thinking?
AB  - BACKGROUND: Ensuring patients receive post-test discussion when collecting HIV
      test results is an integral component of the HIV testing process. New South Wales
      Health Department (NSW Health) policy recommends that all patients be given their
      HIV results in person. We assessed the number of patients who returned for HIV
      test results to Royal Prince Alfred Sexual Health Clinic in Sydney, Australia,
      and predictors of return. METHODS: The files of 218 patients having consecutive
      HIV tests from the beginning of January to the end of April 2007 were manually
      reviewed. Non-consenting patients and those returning to the clinic for another
      reason were excluded. Multivariate logistic regression was used to determine
      factors associated with return for HIV results in person within 4 weeks of having
      the test. RESULTS: Seventy-two of 159 patients (45%) returned for their HIV
      result within 4 weeks of testing. Independent predictors of return were male
      gender (P = 0.041), attending the outreach men-only (v. base) clinic (P = 0.017),
      first HIV test at the clinic (P = 0.002) and sex overseas in the past year (P =
      0.048). CONCLUSION: Over one-half of patients did not collect their HIV results
      in person and thus did not receive any post-test discussion. The strongest
      predictor of return for HIV test results was having a first HIV test at the
      clinic. Current NSW Health policy is failing to achieve high levels of HIV post
      test discussion. For many patients, giving results by telephone may be a more
      appropriate strategy to ensure HIV post-test discussion.

PMID- 20152090
TI  - Pilot of non-invasive (oral fluid) testing for HIV within a community setting.
AB  - BACKGROUND: The present study sought to determine the level of undiagnosed HIV
      infection within a community setting of men who have sex with men (MSM) and
      identify any associated sexual risk behaviours. METHODS: A total of 427 MSM were
      recruited in sex-on-premises venues (SOPV) and gay bars within the inner city of
      Brisbane. An additional 37 MSM were recruited in a smaller, regional centre
      (Toowoomba). Oral fluid testing for HIV antibodies was undertaken using the
      Orasure collection system and assay. Each participant was invited to complete a
      brief behaviour questionnaire and submit an oral fluid specimen. Confirmed
      serology results were linked to reported sexual behaviours, testing patterns and
      HIV status. RESULTS: Of the 464 men surveyed, 33 identified as HIV-positive, and
      all of these were reactive by the Orasure assay. A further eight people who
      identified as negative or unknown serostatus, had confirmed Orasure reactive
      results, resulting in 1.9% of the 'non-HIV positive' MSM sample unaware of their
      positive HIV status. Therefore, 19.5% of the total confirmed HIV-positive
      individuals were not aware of their true serostatus. CONCLUSIONS: A significant
      minority of HIV-positive MSM are currently unaware of their positive serostatus.
      However, an analysis of their risk behaviour does not seem to indicate any
      significant difference to those who are HIV-negative. Interestingly, 86% of those
      who were unaware they were HIV-positive identified that they had been tested in
      the previous 6 months and all of them claimed to have been tested in the previous
      2 years.

PMID- 20152091
TI  - Triple-class HIV antiretroviral therapy failure in an Australian primary care
      setting.
AB  - OBJECTIVE: To determine the prevalence, characteristics and virological outcomes
      of triple-class antiretroviral drug failure (TCF) and triple-class virological
      failure (TCVF) in HIV-infected patients attending an Australian high caseload
      primary care clinic. METHODS: Cross-sectional observational study using a
      retrospective review of electronic medical records from 1007 patients with HIV
      attending Holdsworth House Medical Practice in Darlinghurst, Australia, between
      2007 and 2008. TCF was defined as failure (virological, immunological, clinical,
      intolerance or other) of at least one drug in each of the three major classes of
      highly active antiretroviral therapy. RESULTS: A total of 51 patients (5.1%) with
      TCF were identified. Of these patients, 31.4% had experienced virological failure
      of each of the three main drug classes. Eighty-eight percent of patients with TCF
      and 75% of patients with TCVF had achieved virological suppression (HIV RNA <400
      copies mL(-1)). Total mean (s.d.) duration on antiretroviral therapy (ART) was
      12.2 (3.3) years, with patients receiving an average of 18 antiretroviral drugs
      during this period. Reasons for treatment change included intolerance (88% of
      patients), virological failure (84%), immunological failure (24%) and poor
      adherence (20%). CONCLUSIONS: The prevalence of TCF and TCVF in patients with
      long-term HIV infection and extensive antiretroviral experience is low in primary
      care sites. Despite experiencing failure to the three main classes of ART,
      successful virological outcomes are still achievable in the majority of such
      patients.

PMID- 20152092
TI  - Intimate partner violence and other partner-related factors: correlates of
      sexually transmissible infections and risky sexual behaviours among young adult
      African American women.
AB  - BACKGROUND: Intimate partner violence and other partner-related factors have been
      associated with acquiring sexually transmissible infections (STIs) and engaging
      in risky sexual behaviour. The present study examined partner-related risk
      factors for STIs and risky sexual behaviours among an urban sample of African
      American women. METHODS: African American women, between 18 and 29 years (n =
      848), participated in the study at baseline. Participants completed a 40-min
      Audio Computer Assisted Survey Interview assessing sociodemographics, partner
      related factors and HIV/STI-associated sexual risk behaviours. Subsequently,
      participants provided two vaginal swab specimens for STIs. RESULTS: The findings
      indicated that risky sexual behaviours and STIs were prevalent in this sample:
      35.6% reported a risky sexual partner, 65.4% reported inconsistent condom use and
      17% tested positive for a laboratory-confirmed STI. Women reporting a history of
      intimate partner violence were more likely to report risky sexual partners
      (adjusted odds ratio (AOR) = 2.00; 95% confidence interval (CI) = 1.5-2.8),
      inconsistent condom use (AOR = 1.60; 95% CI = 1.1-2.3) and test positive for an
      STI (AOR = 1.46; 95% CI = 0.99-2.1). Women reporting high partner-related
      barriers to condom use were more likely to report risky sexual partners (AOR =
      1.69; 95% CI = 1.2-2.3), inconsistent condom use (AOR = 2.13; 95% CI = 1.5-3.0)
      and test positive for an STI (AOR = 1.98; 95% CI = 1.3-3.0). Finally, women with
      older partners were more likely to report risky sexual partners (AOR = 1.53; 95%
      CI = 1.1-2.1) and test positive for an STI (AOR = 1.46; 95% CI = 1.0-2.2).
      CONCLUSIONS: This study examines partner-related risk factors for STIs and risky
      sexual behaviours among African American women. These findings underscore the
      need for combined intimate partner violence and HIV/STI prevention programs for
      this disproportionately affected high-risk group.

PMID- 20152093
TI  - Misclassification bias: diversity in conceptualisations about having 'had sex'.
AB  - BACKGROUND: Understanding the signification of the word 'sex' has implications
      for both medical research and clinical practice. Little is known about how people
      of varying ages define sex and how situational qualifiers influence definitions
      across age groups. To our knowledge, this is the first study of a representative
      sample to assess attitudes about which sexual behaviours constitute having 'had
      sex' and to examine possible mediating factors (gender, age, giving/receiving
      stimulation, male ejaculation, female orgasm, condom use or brevity). METHODS: A
      telephone survey of English-speaking residents of Indiana (USA) using random
      digit-dialling produced a final sample of 204 men and 282 women (n = 486) ranging
      in age from 18 to 96 years. Questions assessed the respondents' attitudes on
      manual-genital (MG), oral-genital (OG), penile-vaginal intercourse (PVI) and
      penile-anal intercourse (PAI) behaviours. RESULTS: There was no universal
      consensus on which behaviours constituted having 'had sex'. More than 90%
      responded 'yes' to PVI but one in five responded 'no' to PAI, three in 10
      responded 'no' to OG and about half endorsed MG. Fewer endorsed PVI with no male
      ejaculation (89.1%) compared with PVI without a qualifier (94.8%, P < 0.001). MG
      was endorsed more often when received (48.1%) than given (44.9%, P < 0.001).
      Among men, the oldest and youngest age groups were significantly less likely to
      believe certain behaviours constituted having 'had sex'. CONCLUSIONS: These
      findings highlight the need to use behaviour-specific terminology in sexual
      history taking, sex research, sexual health promotion and sex education.
      Researchers, educators and medical practitioners should exercise caution and not
      assume that their own definitions of having 'had sex' are shared by their
      research participants or patients.

PMID- 20152094
TI  - Young adult sexual health: current and prior sexual behaviours among non-Hispanic
      white US college students.
AB  - BACKGROUND: Less is known about the sexual health of young adults than about
      adolescents, despite 20 to 24-year-olds' greater risk of unintended pregnancy and
      sexually transmissible infections. This paper provides information on college
      students' prior and current sexual practices including oral sex, vaginal
      intercourse, anal intercourse and masturbation. METHODS: We analysed data from a
      cross-sectional sexuality survey of students from two university campuses in the
      USA, one Mid-western and one South-western (n = 1504). The sample consisted of
      non-Hispanic white, never-married students who identified as heterosexual.
      RESULTS: Of 16 possible combinations of four sexual activities (solitary
      masturbation, oral sex, vaginal intercourse and anal intercourse), only four
      contained more than 5% of respondents: masturbation, oral sex and vaginal
      intercourse (37%); oral sex and vaginal intercourse only (20%); all four (14%);
      and none (8%). Twenty percent had ever engaged in anal intercourse. Women were
      significantly less likely than men to have ever masturbated (48 v. 92%). Analyses
      exhibited several sexual health challenges, including lack of verbal sexual
      consent, alcohol use proximal to sex and lack of contraceptive use. CONCLUSIONS:
      Although few young adults are substituting it for vaginal intercourse, anal
      intercourse is increasingly common and safer sex efforts should encourage condom
      use during both sexual activities. Masturbation should be encouraged as an
      alternative to higher risk sexual practices and an essential aspect of sexual
      well being. Finally, practitioners should continue to address specific threats to
      college students' sexual health, including alcohol use and non-verbal consent.

PMID- 20152095
TI  - Aboriginal health worker screening for sexually transmissible infections and
      blood-borne viruses in a rural Australian juvenile correctional facility.
AB  - INTRODUCTION: In Australia, Aboriginal youth are disproportionately represented
      in juvenile detention centres. We assessed the prevalence of sexually
      transmissible infections (STIs) and blood-borne viruses (BBVs) identified by an
      Aboriginal Health Worker (AHW)-led screening program delivered to male detainees
      of a rural juvenile detention centre. METHODS: A retrospective review of first
      screening visit data was performed. Demographic and behavioural data were
      collected and the prevalence of STI/BBV was assessed. RESULTS: Over a 4-year
      period to November 2004, 101 screens on new medium-to-long-term detainees were
      performed. The median age of participants was 17 years (range 14-20) and 87% were
      Aboriginal. Most reported multiple lifetime sexual partners (mean 14, range 0-60)
      and a minority had used a condom for the last episode of vaginal intercourse.
      Injecting drug use and non-professional tattoos or piercings were both reported
      by over one-third of participants, with over 80% reporting previous
      incarceration. One-quarter of those screened were newly diagnosed with one or
      more STI/BBV. The most common infection identified was urethral chlamydia
      (prevalence 16.3%, 95% confidence interval 10.0-25.5%), although the prevalence
      of newly diagnosed syphilis, hepatitis B and hepatitis C were each over 5%. Many
      participants remained susceptible to hepatitis B. CONCLUSION: An AHW-led STI/BBV
      screening program identified a large number of asymptomatic and previously
      undiagnosed infections in this group of young male detainees. Such an education
      and screening program using skilled Aboriginal staff not affiliated with the
      correctional system could have a substantial impact on the prevalence of STI/BBV
      among juvenile detainees.

PMID- 20152096
TI  - Providing high quality information about human papillomavirus for women after
      treatment for high-grade cervical dysplasia.
AB  - BACKGROUND: The present study aimed to inform the production of a resource for
      women who have had a high-grade cervical abnormality and are scheduled to undergo
      testing for human papillomavirus (HPV) at their 12-month follow-up. METHODS: Two
      rounds of semi-structured, qualitative interviews were held with women who were
      attending a gynaecological oncology clinic at a major teaching hospital for women
      in Melbourne, Australia, 6 months after treatment for cervical intraepithelial
      neoplasia (CIN) to receive a follow-up Pap test and colposcopy. In an initial
      round of interviews, we gauged the reactions of 16 women to an existing
      information brochure containing general information about HPV. Based on the
      findings from the interviews, a second brochure aimed specifically for women
      scheduled to undergo HPV testing as part of their post treatment follow-up was
      drafted. Feedback was then gathered from a further 12 women. RESULTS: While all
      participants had received some information and counselling about HPV and HPV
      testing as part of their treatment, many still experienced high levels of stress
      and anxiety about cancer and the sexually transmissible nature of HPV. Many also
      still had unanswered questions about HPV, their treatment regime and future
      prognosis. CONCLUSION: For a brochure to provide an effective adjunct to
      counselling, it is essential that it is carefully developed and pilot tested to
      ensure that it is easily understood and meets the information needs of the target
      audience. Such materials need to provide both medical and psychosocial
      information about HPV and be presented in accessible, easy to understand
      language.

PMID- 20152097
TI  - Prevalence of other sexually transmissible infections in patients with newly
      diagnosed anogenital warts in a sexual health clinic.
AB  - BACKGROUND: Anogenital warts are a common initial presentation to the Canberra
      Sexual Health Centre. It is anticipated that the introduction of human
      papillomavirus vaccination will reduce the incidence of anogenital warts. The
      present study determines the prevalence of other sexually transmissible
      infections in patients newly diagnosed with warts who may not have presented for
      screening without the impetus of a genital lump. METHODS: The prevalence of other
      sexually transmissible infections in new patients presenting to the Canberra
      Sexual Health Centre diagnosed with anogenital warts was determined from a
      retrospective clinical audit from 2002 to 2007. RESULTS: A total of 1015 new
      patients were diagnosed with anogenital warts. Of this total cohort, 53 (5.2%)
      were found to be co-infected with either chlamydia and/or gonorrhoea. Only 13.2%
      of co-infected patients reported symptoms other than genital lumps. Of co
      infected patients 11.3% reported contact with a partner with chlamydia and/or
      gonorrhoea. Not all patients were screened for other sexually transmissible
      infections: 762 (75.1%) were screened for chlamydia and 576 (56.7%) were screened
      for gonorrhoea. Of those tested, 6.8% of men and 6.9% of women were positive for
      chlamydia highlighting the importance of offering full sexually transmissible
      infection screening in those newly diagnosed with anogenital warts. Chlamydia was
      more common in younger patients who reported a higher number of sexual partners.
      CONCLUSIONS: It is anticipated that human papillomavirus vaccination will lead to
      a decline in anogenital wart incidence as well as other human papillomavirus
      associated disease. Although one opportunity for testing for other sexually
      transmissible infections may be lost in this population, the decrease in
      anogenital warts will leave clinicians with more time to pursue other screening
      programs. Education and screening campaigns should continue to focus on the
      asymptomatic nature of the majority of sexually transmissible infections.

PMID- 20152098
TI  - 'Show me the money': financial incentives increase chlamydia screening rates
      among tertiary students: a pilot study.
AB  - BACKGROUND: We hypothesise that text-messaging and financial incentives would
      increase tertiary student participation in chlamydia screening. METHODS: A cross
      sectional study was conducted over two phases on eight tertiary campuses during
      2007. During Phase 1 (6 months) study activities were advertised through student
      organisations and media. Education and screening were offered during a range of
      student activities. During Phase 2 (4 days) education and screening were offered
      via text messages. Non-financial incentives were offered during Phase 1 and a $10
      cash incentive was offered during Phase 2. Rates of specimens provided by
      students and the direct costs incurred during each phase were compared. RESULTS:
      2786 students attended the 31 activities conducted in Phase 1. Of these, 627
      students (22.5%) provided urine specimens for chlamydia testing. During Phase 2,
      the dissemination of 866 text messages resulted in urine specimens from 392
      students (45.3%). Costs per test were AUD $175.11 in Phase 1 and AUD $27.13 in
      Phase 2. CONCLUSIONS: Compared with more labour intensive (and therefore more
      expensive) screening activities conducted over a 6-month period, offering a small
      financial incentive to tertiary students through text messaging over a 4-day
      period significantly increased participation in on-campus chlamydia screening.
      This model could readily be applied to other populations to increase
      participation in chlamydia screening.

PMID- 20152099
TI  - Problems with condoms may be reduced for men taking ample time to apply them.
AB  - BACKGROUND: One potentially important antecedent of experiencing problems with
      condom use during penile-vaginal sex is the amount of time that men (and perhaps
      women) allow for condom application. To examine whether men reporting that ample
      time was available to apply a male condom (the last time a condom was used for
      penile-vaginal sex) were also less likely to report problems with condom use such
      as breakage, slippage and erection difficulties during that sexual event.
      METHODS: A convenience sample of men (n = 440) was recruited via advertisements
      in newspapers (two urban and one small town) and a blog on the website of a
      condom sales company. Men completed a questionnaire posted on the website of The
      Kinsey Institute for Research in Sex, Gender, and Reproduction. Inclusion
      criteria were that participants were: at least 18 years old; used condoms for
      penile-vaginal intercourse in the past 3 months; and able to read English.
      RESULTS: In controlled, event-specific analyses, men reporting that they did not
      have sufficient time for condom application were ~three times more likely to
      report breakage and approximately 2.4 times more likely to report slippage. In
      addition, men who reported that they lacked time for condom application were
      approximately 2.4 times more likely to experience any of nine sexual problems,
      3.4 times more likely to report difficulty with erection, 2.1 times more likely
      to report reduced sexual pleasure, 2.2 times more likely to report reduced sexual
      pleasure of their female partner and 2.6 times more likely to report that the
      condom irritated their partner's vagina. CONCLUSIONS: This is the first study
      using an event-specific analysis to examine the effect of not having enough time
      for condom application on condom breakage, slippage and several outcomes related
      to sexual pleasure. Sexually transmissible infections and pregnancy prevention
      messages should include recommendations to men to take their time applying
      condoms.

PMID- 20152100
TI  - A cross-sectional study of reported symptoms for sexually transmissible
      infections among female sex workers in Papua New Guinea.
AB  - BACKGROUND: Sexually transmissible infections (STIs) are common in female sex
      workers (FSWs), most of which are asymptomatic and therefore under-reported. Our
      aim was to determine the sensitivity and specificity of reported symptoms
      obtained via questionnaire augmented with leukocyte esterase (LE) urine dipstick
      test for the detection of Chlamydia trachomatis (Ct), Neisseria gonorrhea (Ng)
      and Trichomonas vaginalis (Tv) detected using polymerase chain reaction (PCR).
      METHODS: In November 2003, a cohort of FSWs was screened for STIs and completed a
      questionnaire. RESULTS: We enrolled 129 FSWs (90% participation rate) of whom 48
      (37%), 30 (23%) and 53 (41%) were diagnosed with Ng, Ct and Tv, respectively, by
      PCR. Of those diagnosed with any of these infections, 78% reported anogenital
      symptoms and of those without infections, 28% reported symptoms. Anogenital
      symptoms were present in over 50% FSWs. Genital odour (present in 26%), lower
      abdominal pain (present in 29%), dysuria (present in 19%) had a sensitivity
      around (50%), specificity (>80%) and all were significantly associated with
      positive PCR results for individual organisms; however, the sensitivity of these
      symptoms to detect the presence of any positive PCR result was low (<50%). When
      LE urine dipstick test result of >1 was combined with the presence of three
      reported symptoms the sensitivity was 86%, specificity of 73% and a positive
      predictive value of 72%; a better predictor of infections. CONCLUSIONS: Our
      finding suggest an approach that incorporates LE urine dipstick test >1 and
      multiple symptoms may be a feasible option for screening infections among FSWs in
      resource constraint settings.

PMID- 20152101
TI  - A case-control study of men with non-gonococcal urethritis at Auckland Sexual
      Health Service: rates of detection of Mycoplasma genitalium.
AB  - BACKGROUND: Previous studies have identified Mycoplasma genitalium as a cause of
      urethritis in men. As there is no New Zealand data, a case-control study was
      conducted to determine whether this organism is a significant cause of urethritis
      in men presenting to Auckland Sexual Health Service. METHODS: Enrollment for the
      study commenced in March 2006 and finished in February 2008. Inclusion criteria
      for cases of non-gonococcal urethritis were onset of urethritis symptoms within
      one month confirmed by urethral Gram staining showing >or=10 polymorphonuclear
      leucocytes per high-powered field. Controls were men presenting during the same
      time period for asymptomatic sexual health screening. All participants were
      tested for Neisseria gonorrhoeae, M. genitalium, and Chlamydia trachomatis.
      Information regarding symptoms, sexual behaviour and treatment was collected
      using a standard questionnaire. RESULTS: We recruited 209 cases and 199 controls
      with a participation rate of 96%. The prevalence of C. trachomatis and M.
      genitalium in non-gonococcal urethritis cases was 33.5% and 10% respectively. Co
      infection with these organisms was uncommon (1.9%). C. trachomatis and M.
      genitalium were diagnosed in 4% and 2% of controls, respectively, and both
      infections were detected significantly less often than in the cases (P < 0.0001,
      P < 0.005). Cases were more likely to report inconsistent condom use, multiple
      sexual contacts and not having sexual intercourse in the last week (P = 0.03, P =
      0.02, P = 0.03). A past history of non-gonococcal urethritis was a significant
      predictor of current symptoms (P < 0.0001). CONCLUSIONS: This is the first study
      to investigate M. genitalium infection in New Zealand men. Our results confirm
      that M. genitalium is a cause of non-gonococcal urethritis in men presenting to
      our service.

PMID- 20152102
TI  - A case of apparent resistance to all available antiretroviral drugs in a HIV
      positive patient.
AB  - We describe a case of multidrug and class resistant HIV in a patient with
      psychological issues affecting his adherence. The complexities involved in
      subsequent treatment decisions when resistance interpretation algorithms are
      discordant are discussed.

PMID- 20152103
TI  - Risk factors for herpes simplex virus type 2 and its association with HIV among
      pregnant teenagers in Zimbabwe.
AB  - Herpes simplex virus type 2 (HSV-2) causes a chronic infection that is recognised
      as the leading cause of genital ulcer disease worldwide and is known to increase
      the risk of HIV infection. In a cross-sectional study we examined risk factors
      for HSV-2 among 176 pregnant teenagers recruited from three primary health care
      clinics in Zimbabwe. The prevalence of HSV-2 and HIV were 41.6% and 29.2%
      respectively. HIV-infected teenagers were more likely to be HSV-2 seropositive
      compared with the HIV uninfected teenagers, odds ratio (OR) 7.9 (95% confidence
      interval (CI) 3.7-16.9). In multivariate analysis having an older partner
      remained independently associated with HSV-2 seropositivity, OR 2.9 (95% CI 1.2
      6.9) suggesting that risk factors for HSV-2 seropositivity among pregnant
      teenagers depend primarily on the behaviour of the male partners.

PMID- 20152104
TI  - Is screening asymptomatic men who have sex with men for urethral gonorrhoea
      worthwhile?
AB  - We determined the prevalence of symptomatic and asymptomatic urethral gonorrhoea
      among men who have sex with men (MSM) at our Australian sexual health clinic.
      Asymptomatic MSM are screened using the Roche Amplicor((R)) PCR, whereas culture
      is used for symptomatic MSM. We analysed data from all MSM tested for urethral
      gonorrhoea from March 2006 to July 2008. Among the 4453 asymptomatic MSM, there
      were two (0.04%) diagnoses of urethral gonorrhoea, compared with 38 (3.13%) among
      1213 symptomatic MSM. Despite a high prevalence of symptomatic infection,
      asymptomatic urethral gonococcal infection was extremely uncommon among MSM seen
      in our sexual health clinic.

PMID- 20152106
TI  - Altered function of the serotonin 1A autoreceptor and the antidepressant
      response.
AB  - In this issue of Neuron, Richardson-Jones et al. report on a novel genetic
      approach to conditionally and specifically dampen the function of the 5-HT(1A)
      autoreceptor in mice to study its role on the 5-HT system and on the
      antidepressant-like effect of the selective serotonin reuptake inhibitor (SSRI)
      fluoxetine.

PMID- 20152107
TI  - alpha-Synuclein at the synaptic gate.
AB  - Only doubling or tripling alpha-synuclein expression significantly increases the
      risk of developing Parkinson's disease. In this issue of Neuron, Nemani et al.
      show that this modest overexpression of alpha-synuclein does not lead to obvious
      toxicity in the near term, but impairs glutamate and dopamine release,
      potentially leading to broad network dysfunction and eventual pathology.

PMID- 20152105
TI  - The emergence of parvoviruses of carnivores.
AB  - The emergence of canine parvovirus (CPV) represents a well-documented example
      highlighting the emergence of a new virus through cross-species transmission. CPV
      emerged in the mid-1970s as a new pathogen of dogs and has since become endemic
      in the global dog population. Despite widespread vaccination, CPV has remained a
      widespread disease of dogs, and new genetic and antigenic variants have arisen
      and sometimes reached high frequency in certain geographic regions or throughout
      the world. Here we review our understanding of this emergence event and contrast
      it to what is known about the emergence of a disease in mink caused by mink
      enteritis virus (MEV). In addition, we summarize the evolution of CPV over the
      past 30 years in the global dog population, and describe the epidemiology of
      contemporary parvovirus infections of dogs and cats. CPV represents a valuable
      model for understanding disease emergence through cross-species transmission,
      while MEV provides an interesting comparison.

PMID- 20152108
TI  - The dance of the perivascular and endothelial cells: mechanisms of brain response
      to immune signaling.
AB  - The mechanisms underlying the brain response to systemic inflammation remain
      unclear. In this issue of Neuron, Serrats and colleagues demonstrate that two
      cell types that produce prostaglandins that act on the brain, perivascular and
      endothelial cells, have an unexpectedly complex interaction in regulating the
      timing and types of brain responses that occur.

PMID- 20152109
TI  - Are the dorsal and ventral hippocampus functionally distinct structures?
AB  - One literature treats the hippocampus as a purely cognitive structure involved in
      memory; another treats it as a regulator of emotion whose dysfunction leads to
      psychopathology. We review behavioral, anatomical, and gene expression studies
      that together support a functional segmentation into three hippocampal
      compartments: dorsal, intermediate, and ventral. The dorsal hippocampus, which
      corresponds to the posterior hippocampus in primates, performs primarily
      cognitive functions. The ventral (anterior in primates) relates to stress,
      emotion, and affect. Strikingly, gene expression in the dorsal hippocampus
      correlates with cortical regions involved in information processing, while genes
      expressed in the ventral hippocampus correlate with regions involved in emotion
      and stress (amygdala and hypothalamus).

PMID- 20152110
TI  - Cortical maps and white matter tracts following long period of visual deprivation
      and retinal image restoration.
AB  - Abnormal visual input during development has dramatic effects on the visual
      system. How does the adult visual system respond when input is corrected? MM lost
      his left eye and became blind in the right due to corneal damage at the age of 3.
      At age 46, MM regained his retinal image, but his visual abilities, even seven
      years following the surgery, remain severely limited, and he does not rely on
      vision for daily life. Neuroimaging measurements reveal several differences among
      MM, sighted controls, sighted monocular, and early blind subjects. We speculate
      that these differences stem from damage during the critical period in development
      of retinal neurons with small, foveal receptive fields. In this case, restoration
      of functional vision requires more than improving retinal image contrast. In
      general, visual restoration will require accounting for the developmental
      trajectory of the individual and the consequences of the early deprivation on
      cortical circuitry.

PMID- 20152111
TI  - Genetically increased cell-intrinsic excitability enhances neuronal integration
      into adult brain circuits.
AB  - New neurons are added to the adult brain throughout life, but only half
      ultimately integrate into existing circuits. Sensory experience is an important
      regulator of the selection of new neurons but it remains unknown whether
      experience provides specific patterns of synaptic input or simply a minimum level
      of overall membrane depolarization critical for integration. To investigate this
      issue, we genetically modified intrinsic electrical properties of adult-generated
      neurons in the mammalian olfactory bulb. First, we observed that suppressing
      levels of cell-intrinsic neuronal activity via expression of ESKir2.1 potassium
      channels decreases, whereas enhancing activity via expression of NaChBac sodium
      channels increases survival of new neurons. Neither of these modulations affects
      synaptic formation. Furthermore, even when neurons are induced to fire
      dramatically altered patterns of action potentials, increased levels of cell
      intrinsic activity completely blocks cell death triggered by NMDA receptor
      deletion. These findings demonstrate that overall levels of cell-intrinsic
      activity govern survival of new neurons and precise firing patterns are not
      essential for neuronal integration into existing brain circuits.

PMID- 20152112
TI  - 5-HT1A autoreceptor levels determine vulnerability to stress and response to
      antidepressants.
AB  - Most depressed patients don't respond to their first drug treatment, and the
      reasons for this treatment resistance remain enigmatic. Human studies implicate a
      polymorphism in the promoter of the serotonin-1A (5-HT(1A)) receptor gene in
      increased susceptibility to depression and decreased treatment response. Here we
      develop a new strategy to manipulate 5-HT(1A) autoreceptors in raphe nuclei
      without affecting 5-HT(1A) heteroreceptors, generating mice with higher (1A-High)
      or lower (1A-Low) autoreceptor levels. We show that this robustly affects raphe
      firing rates, but has no effect on either basal forebrain serotonin levels or
      conflict-anxiety measures. However, compared to 1A-Low mice, 1A-High mice show a
      blunted physiological response to acute stress, increased behavioral despair, and
      no behavioral response to antidepressant, modeling patients with the 5-HT(1A)
      risk allele. Furthermore, reducing 5-HT(1A) autoreceptor levels prior to
      antidepressant treatment is sufficient to convert nonresponders into responders.
      These results establish a causal relationship between 5-HT(1A) autoreceptor
      levels, resilience under stress, and response to antidepressants.

PMID- 20152113
TI  - Delivery of GABAARs to synapses is mediated by HAP1-KIF5 and disrupted by mutant
      huntingtin.
AB  - The density of GABA(A) receptors (GABA(A)Rs) at synapses regulates brain
      excitability, and altered inhibition may contribute to Huntington's disease,
      which is caused by a polyglutamine repeat in the protein huntingtin. However, the
      machinery that delivers GABA(A)Rs to synapses is unknown. We demonstrate that
      GABA(A)Rs are trafficked to synapses by the kinesin family motor protein 5
      (KIF5). We identify the adaptor linking the receptors to KIF5 as the huntingtin
      associated protein 1 (HAP1). Disrupting the HAP1-KIF5 complex decreases synaptic
      GABA(A)R number and reduces the amplitude of inhibitory postsynaptic currents.
      When huntingtin is mutated, as in Huntington's disease, GABA(A)R transport and
      inhibitory synaptic currents are reduced. Thus, HAP1-KIF5-dependent GABA(A)R
      trafficking is a fundamental mechanism controlling the strength of synaptic
      inhibition in the brain. Its disruption by mutant huntingtin may explain some of
      the defects in brain information processing occurring in Huntington's disease and
      provides a molecular target for therapeutic approaches.

PMID- 20152114
TI  - Increased expression of alpha-synuclein reduces neurotransmitter release by
      inhibiting synaptic vesicle reclustering after endocytosis.
AB  - The protein alpha-synuclein accumulates in the brain of patients with sporadic
      Parkinson's disease (PD), and increased gene dosage causes a severe, dominantly
      inherited form of PD, but we know little about the effects of synuclein that
      precede degeneration. alpha-Synuclein localizes to the nerve terminal, but the
      knockout has little if any effect on synaptic transmission. In contrast, we now
      find that the modest overexpression of alpha-synuclein, in the range predicted
      for gene multiplication and in the absence of overt toxicity, markedly inhibits
      neurotransmitter release. The mechanism, elucidated by direct imaging of the
      synaptic vesicle cycle, involves a specific reduction in size of the synaptic
      vesicle recycling pool. Ultrastructural analysis demonstrates reduced synaptic
      vesicle density at the active zone, and imaging further reveals a defect in the
      reclustering of synaptic vesicles after endocytosis. Increased levels of alpha
      synuclein thus produce a specific, physiological defect in synaptic vesicle
      recycling that precedes detectable neuropathology.

PMID- 20152115
TI  - SynDIG1: an activity-regulated, AMPA- receptor-interacting transmembrane protein
      that regulates excitatory synapse development.
AB  - During development of the central nervous system, precise synaptic connections
      between presynaptic and postsynaptic neurons are formed. While significant
      progress has been made in our understanding of AMPA receptor trafficking during
      synaptic plasticity, less is known about the molecules that recruit AMPA
      receptors to nascent synapses during synaptogenesis. Here we identify a type II
      transmembrane protein (SynDIG1) that regulates AMPA receptor content at
      developing synapses in dissociated rat hippocampal neurons. SynDIG1 colocalizes
      with AMPA receptors at synapses and at extrasynaptic sites and associates with
      AMPA receptors in heterologous cells and brain. Altered levels of SynDIG1 in
      cultured neurons result in striking changes in excitatory synapse number and
      function. SynDIG1-mediated synapse development is dependent on association with
      AMPA receptors via its extracellular C terminus. Intriguingly, SynDIG1 content in
      dendritic spines is regulated by neuronal activity. Altogether, we define SynDIG1
      as an activity-regulated transmembrane protein that regulates excitatory synapse
      development.

PMID- 20152116
TI  - Dual roles for perivascular macrophages in immune-to-brain signaling.
AB  - Cytokines produced during infection/inflammation activate adaptive central
      nervous system (CNS) responses, including acute stress responses mediated by the
      hypothalamo-pituitary-adrenal (HPA) axis. The mechanisms by which cytokines
      engage HPA control circuitry remain unclear, though stimulated release of
      prostanoids from neighboring vascular cells has been implicated in this regard.
      How specific vascular cell types, endothelial cells (ECs) versus perivascular
      cells (PVCs; a subset of brain-resident macrophages), participate in this
      response remains unsettled. We exploited the phagocytic activity of PVCs to
      deplete them in rats by central injection of a liposome-encapsulated proapoptotic
      drug. This manipulation abrogated CNS and hormonal indices of HPA activation
      under immune challenge conditions (interleukin-1) that activated prostanoid
      synthesis only in PVCs, while enhancing these responses to stimuli
      (lipopolysaccharide) that engaged prostanoid production by ECs as well. Thus,
      PVCs provide both prostanoid-mediated drive to the HPA axis and an anti
      inflammatory action that constrains endothelial and overall CNS responses to
      inflammatory insults.

PMID- 20152117
TI  - Synaptic and network mechanisms of sparse and reliable visual cortical activity
      during nonclassical receptive field stimulation.
AB  - During natural vision, the entire visual field is stimulated by images rich in
      spatiotemporal structure. Although many visual system studies restrict stimuli to
      the classical receptive field (CRF), it is known that costimulation of the CRF
      and the surrounding nonclassical receptive field (nCRF) increases neuronal
      response sparseness. The cellular and network mechanisms underlying increased
      response sparseness remain largely unexplored. Here we show that combined CRF +
      nCRF stimulation increases the sparseness, reliability, and precision of spiking
      and membrane potential responses in classical regular spiking (RS(C)) pyramidal
      neurons of cat primary visual cortex. Conversely, fast-spiking interneurons
      exhibit increased activity and decreased selectivity during CRF + nCRF
      stimulation. The increased sparseness and reliability of RS(C) neuron spiking is
      associated with increased inhibitory barrages and narrower visually evoked
      synaptic potentials. Our experimental observations were replicated with a simple
      computational model, suggesting that network interactions among neuronal subtypes
      ultimately sharpen recurrent excitation, producing specific and reliable visual
      responses.

PMID- 20152118
TI  - Manipulation of a central auditory representation shapes learned vocal output.
AB  - Learned vocalizations depend on the ear's ability to monitor and ultimately
      instruct the voice. Where is auditory feedback processed in the brain, and how
      does it modify motor networks for learned vocalizations? Here we addressed these
      questions using singing-triggered microstimulation and chronic recording methods
      in the singing zebra finch, a small songbird that relies on auditory feedback to
      learn and maintain its species-typical vocalizations. Manipulating the singing
      related activity of feedback-sensitive thalamic neurons subsequently triggered
      vocal plasticity, constraining the central pathway and functional mechanisms
      through which feedback-related information shapes vocalization.

PMID- 20152119
TI  - Mechanisms underlying dopamine-mediated reward bias in compulsive behaviors.
AB  - Pathological behaviors such as problem gambling or shopping are characterized by
      compulsive choice despite alternative options and negative costs. Reinforcement
      learning algorithms allow a computation of prediction error, a comparison of
      actual and expected outcomes, which updates our predictions and influences our
      subsequent choices. Using a reinforcement learning model, we show data consistent
      with the idea that dopamine agonists in susceptible individuals with Parkinson's
      disease increase the rate of learning from gain outcomes. Dopamine agonists also
      increase striatal prediction error activity, thus signifying a "better than
      expected" outcome. Thus, our findings are consistent with a model whereby a
      distorted estimation of the gain cue underpins a choice bias toward gains.

PMID- 20152120
TI  - Kalzium ist nicht alles.
AB  - Elevation of cerebral Mg2+ with a novel orally delivered ionophore, magnesium
      threonate, enhances cognition in young and old rats over a 12-24 day treatment
      interval, as outlined in a paper by Slutsky et al. in this issue of Neuron.
      Despite both Mg2+ and Zn2+ blocking the NMDA receptor channel, sustained
      extracellular Mg2+ elevation mimics sustained synaptic Zn2+ concentrations by
      increasing hippocampal NR2B expression and bouton density.

PMID- 20152121
TI  - Location, location, location: contrasting roles of synaptic and extrasynaptic
      NMDA receptors in Huntington's disease.
AB  - Abnormally enhanced N-methyl-D-aspartate (NMDA) receptor function is implicated
      in Huntington's disease (HD). In this issue of Neuron and a recent issue of
      Nature Medicine, an abnormal balance between the activity of NMDA receptors at
      synaptic (prosurvival) and extrasynaptic (proapoptotic) sites has been uncovered
      in a cellular and a mouse model of HD.

PMID- 20152122
TI  - Excitatory neuromodulator reduces dopamine release, enhancing prolactin
      secretion.
AB  - Hypothalamic dopamine neurons inhibit pituitary prolactin secretion. In this
      issue of Neuron, Lyons et al. provide evidence for a novel model, whereby the
      excitatory neuropeptide TRH depolarizes gap-junction-coupled dopamine neurons,
      leading to a shift in the population pattern of action potentials from phasic
      burst firing to regular tonic firing, hypothetically reducing dopamine release
      while increasing total spike number.

PMID- 20152123
TI  - Eye smarter than scientists believed: neural computations in circuits of the
      retina.
AB  - We rely on our visual system to cope with the vast barrage of incoming light
      patterns and to extract features from the scene that are relevant to our well
      being. The necessary reduction of visual information already begins in the eye.
      In this review, we summarize recent progress in understanding the computations
      performed in the vertebrate retina and how they are implemented by the neural
      circuitry. A new picture emerges from these findings that helps resolve a vexing
      paradox between the retina's structure and function. Whereas the conventional
      wisdom treats the eye as a simple prefilter for visual images, it now appears
      that the retina solves a diverse set of specific tasks and provides the results
      explicitly to downstream brain areas.

PMID- 20152124
TI  - Enhancement of learning and memory by elevating brain magnesium.
AB  - Learning and memory are fundamental brain functions affected by dietary and
      environmental factors. Here, we show that increasing brain magnesium using a
      newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the
      enhancement of learning abilities, working memory, and short- and long-term
      memory in rats. The pattern completion ability was also improved in aged rats.
      MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive
      puncta in DG and CA1 subregions of hippocampus that were correlated with memory
      improvement. Functionally, magnesium increased the number of functional
      presynaptic release sites, while it reduced their release probability. The
      resultant synaptic reconfiguration enabled selective enhancement of synaptic
      transmission for burst inputs. Coupled with concurrent upregulation of NR2B
      containing NMDA receptors and its downstream signaling, synaptic plasticity
      induced by correlated inputs was enhanced. Our findings suggest that an increase
      in brain magnesium enhances both short-term synaptic facilitation and long-term
      potentiation and improves learning and memory functions.

PMID- 20152125
TI  - Early increase in extrasynaptic NMDA receptor signaling and expression
      contributes to phenotype onset in Huntington's disease mice.
AB  - N-methyl-D-aspartate receptor (NMDAR) excitotoxicity is implicated in the
      pathogenesis of Huntington's disease (HD), a late-onset neurodegenerative
      disorder. However, NMDARs are poor therapeutic targets, due to their essential
      physiological role. Recent studies demonstrate that synaptic NMDAR transmission
      drives neuroprotective gene transcription, whereas extrasynaptic NMDAR activation
      promotes cell death. We report specifically increased extrasynaptic NMDAR
      expression, current, and associated reductions in nuclear CREB activation in HD
      mouse striatum. The changes are observed in the absence of dendritic
      morphological alterations, before and after phenotype onset, correlate with
      mutation severity, and require caspase-6 cleavage of mutant huntingtin. Moreover,
      pharmacological block of extrasynaptic NMDARs with memantine reversed signaling
      and motor learning deficits. Our data demonstrate elevated extrasynaptic NMDAR
      activity in an animal model of neurodegenerative disease. We provide a candidate
      mechanism linking several pathways previously implicated in HD pathogenesis and
      demonstrate successful early therapeutic intervention in mice.

PMID- 20152126
TI  - Hook3 interacts with PCM1 to regulate pericentriolar material assembly and the
      timing of neurogenesis.
AB  - Centrosome functions are important in multiple brain developmental processes.
      Proper functioning of the centrosome relies on assembly of protein components
      into the pericentriolar material. This dynamic assembly is mediated by the
      trafficking of pericentriolar satellites, which are comprised of centrosomal
      proteins. Here we demonstrate that trafficking of pericentriolar satellites
      requires the interaction between Hook3 and Pericentriolar Material 1 (PCM1).
      Hook3, previously shown to link the centrosome and the nucleus in C. elegans, is
      recruited to pericentriolar satellites through interaction with PCM1, a protein
      associated with schizophrenia. Disruption of the Hook3-PCM1 interaction in vivo
      impairs interkinetic nuclear migration, a featured behavior of embryonic neural
      progenitors. This in turn leads to overproduction of neurons and premature
      depletion of the neural progenitor pool in the developing neocortex. These
      results underscore the importance of centrosomal assembly in neurogenesis and
      provide potential insights into the etiology of brain developmental diseases
      related to the centrosome dysfunction.

PMID- 20152127
TI  - Ephexin1 is required for structural maturation and neurotransmission at the
      neuromuscular junction.
AB  - The maturation of neuromuscular junctions (NMJs) requires the topological
      transformation of postsynaptic acetylcholine receptor (AChR)-containing
      structures from a simple plaque to an elaborate structure composed of pretzel
      like branches. This maturation process results in the precise apposition of the
      presynaptic and postsynaptic specializations. However, little is known about the
      molecular mechanisms underlying the plaque-to-pretzel transition of AChR
      clusters. In this study, we identify an essential role for the RhoGEF ephexin1 in
      the maturation of AChR clusters. Adult ephexin1(-/-) mice exhibit severe muscle
      weakness and impaired synaptic transmission at the NMJ. Intriguingly, when
      ephexin1 expression is deficient in vivo, the NMJ fails to mature into the
      pretzel-like shape, and such abnormalities can be rescued by re-expression of
      ephexin1. We further demonstrate that ephexin1 regulates the stability of AChR
      clusters in a RhoA-dependent manner. Taken together, our findings reveal an
      indispensible role for ephexin1 in regulating the structural maturation and
      neurotransmission of NMJs.

PMID- 20152128
TI  - Synchronized network oscillations in rat tuberoinfundibular dopamine neurons:
      switch to tonic discharge by thyrotropin-releasing hormone.
AB  - The pituitary hormone, prolactin, triggers lactation in nursing mothers. Under
      nonlactating conditions, prolactin secretion is suppressed by powerful inhibition
      from hypothalamic tuberoinfundibular dopamine (TIDA) neurons. Although firing
      pattern has been suggested as integral to neuroendocrine control, the electrical
      behavior of TIDA cells remains unknown. We demonstrate that rat TIDA neurons
      discharge rhythmically in a robust 0.05 Hz oscillation. The oscillation is phase
      locked between neurons, and while it persists during chemical synaptic
      transmission blockade, it is abolished by gap junction antagonists. Thyrotropin
      releasing hormone (TRH) potently stimulates prolactin release, an effect assumed
      to take place in the pituitary. In TIDA cells, TRH caused a transition from
      phasic to tonic firing through combined pre- and postsynaptic effects. These
      findings suggest a model for prolactin regulation where a TIDA network switch
      from oscillations to sustained discharge converts dopamine from an antagonist at
      high concentrations to a functional agonist as dopamine output from the network
      decreases.

PMID- 20152129
TI  - Pathway-specific feedforward circuits between thalamus and neocortex revealed by
      selective optical stimulation of axons.
AB  - Thalamocortical and corticothalamic pathways mediate bidirectional communication
      between the thalamus and neocortex. These pathways are entwined, making their
      study challenging. Here we used lentiviruses to express channelrhodopsin-2
      (ChR2), a light-sensitive cation channel, in either thalamocortical or
      corticothalamic projection cells. Infection occurred only locally, but efferent
      axons and their terminals expressed ChR2 strongly, allowing selective optical
      activation of each pathway. Laser stimulation of ChR2-expressing thalamocortical
      axons/terminals evoked robust synaptic responses in cortical excitatory cells and
      fast-spiking (FS) inhibitory interneurons, but only weak responses in
      somatostatin-containing interneurons. Strong FS cell activation led to
      feedforward inhibition in all cortical neuron types, including FS cells.
      Corticothalamic stimulation excited thalamic relay cells and inhibitory neurons
      of the thalamic reticular nucleus (TRN). TRN activation triggered inhibition in
      relay cells but not in TRN neurons. Thus, a major difference between
      thalamocortical and corticothalamic processing was the extent to which
      feedforward inhibitory neurons were themselves engaged by feedforward inhibition.

PMID- 20152130
TI  - Critical period plasticity matches binocular orientation preference in the visual
      cortex.
AB  - Changes of ocular dominance in the visual cortex can be induced by visual
      manipulations during a critical period in early life. However, the role of
      critical period plasticity in normal development is unknown. Here we show that at
      the onset of this time window, the preferred orientations of individual cortical
      cells in the mouse are mismatched through the two eyes and the mismatch decreases
      and reaches adult levels by the end of the period. Deprivation of visual
      experience during this period irreversibly blocks the binocular matching of
      orientation preference, but has no effect in adulthood. The critical period of
      binocular matching can be delayed by long-term visual deprivation from birth,
      like that of ocular dominance plasticity. These results demonstrate that activity
      dependent changes induced by normal visual experience during the well-studied
      critical period serve to match eye-specific inputs in the cortex, thus revealing
      a physiological role for critical period plasticity during normal development.

PMID- 20152131
TI  - Synchronized activity between the ventral hippocampus and the medial prefrontal
      cortex during anxiety.
AB  - The ventral hippocampus, unlike its dorsal counterpart, is required for anxiety
      like behavior. The means by which it acts are unknown. We hypothesized that the
      hippocampus synchronizes with downstream targets that influence anxiety, such as
      the medial prefrontal cortex (mPFC). To test this hypothesis, we recorded mPFC
      and hippocampal activity in mice exposed to two anxiogenic arenas. Theta
      frequency activity in the mPFC and ventral, but not dorsal, hippocampus was
      highly correlated at baseline, and this correlation increased in both anxiogenic
      environments. Increases in mPFC theta power predicted avoidance of the aversive
      compartments of each arena and were larger in serotonin 1A receptor knockout
      mice, a genetic model of increased anxiety-like behavior. These results suggest a
      role for theta-frequency synchronization between the ventral hippocampus and the
      mPFC in anxiety. They are consistent with the notion that such synchronization is
      a general mechanism by which the hippocampus communicates with downstream
      structures of behavioral relevance.

PMID- 20152132
TI  - A disynaptic relay from superior colliculus to dorsal stream visual cortex in
      macaque monkey.
AB  - The superior colliculus (SC) is the first station in a subcortical relay of
      retinal information to extrastriate visual cortex. Ascending SC projections pass
      through pulvinar and LGN on their way to cortex, but it is not clear how many
      synapses are required to complete these circuits or which cortical areas are
      involved. To examine this relay directly, we injected transynaptic rabies virus
      into several extrastriate visual areas. We observed disynaptically labeled cells
      in superficial, retino-recipient SC layers from injections in dorsal stream areas
      MT and V3, but not the earliest extrastriate area, V2, nor ventral stream area
      V4. This robust SC-dorsal stream pathway is most likely relayed through the
      inferior pulvinar and can provide magnocellular-like sensory inputs necessary for
      motion perception and the computation of orienting movements. Furthermore, by
      circumventing primary visual cortex, this pathway may also underlie the remaining
      visual capacities associated with blindsight.

PMID- 20152134
TI  - The mushroom body.

PMID- 20152133
TI  - Enhanced brain correlations during rest are related to memory for recent
      experiences.
AB  - Long-term storage of episodic memories is hypothesized to result from the off
      line transfer of information from the hippocampus to neocortex, allowing a
      hippocampal-independent cortical representation to emerge. However, off-line
      hippocampal-cortical interactions have not been demonstrated to be linked with
      long-term memory. Here, using functional magnetic resonance imaging, we examined
      if hippocampal-cortical BOLD correlations during rest following an associative
      encoding task are related to later associative memory performance. Our data show
      enhanced functional connectivity between the hippocampus and a portion of the
      lateral occipital complex (LO) during rest following a task with high subsequent
      memory compared to pretask baseline resting connectivity. This effect is not seen
      during rest following a task with poor subsequent memory. Furthermore, the
      magnitude of hippocampal-LO correlations during posttask rest predicts individual
      differences in later associative memory. These results demonstrate the importance
      of postexperience resting brain correlations for memory for recent experiences.

PMID- 20152135
TI  - Host-pathogen interactions: proline gives insect pathogens the green light.
AB  - How does a quiescent symbiont of a nematode worm know when to turn nasty?
      Metabolic analysis and genetic knockouts confirm that model insect pathogens can
      sense L-proline in insect blood. This not only serves as a wake-up call,
      activating secondary metabolite virulence factors, but also provides an energy
      source for a metabolic shift appropriate for adaptation to the host environment.

PMID- 20152136
TI  - Genetic adaptation: a new piece for a very old puzzle.
AB  - Does stress create mutations or only serve as an agent of natural selection? New
      experiments reveal effects of transcription and temperature on the response to
      growth limitation and could help resolve a 150-year-old debate.

PMID- 20152137
TI  - Visuomotor control: not so simple insect locomotion.
AB  - Observations of locusts walking on a horizontal ladder demonstrate that front leg
      movements are targeted by visual and antennal cues, suggesting sophisticated
      motor control mechanisms for these seemingly simple animals.

PMID- 20152138
TI  - Transcriptional memory: staying in the loop.
AB  - Actively transcribed genes are organized into loops in which the 5' and 3' ends
      of the gene physically associate. Two new papers show that gene looping can
      persist after genes are repressed, promoting rapid reactivation of transcription,
      a phenomenon known as transcriptional memory.

PMID- 20152139
TI  - Multisensory integration: vision boosts information through suppression in
      auditory cortex.
AB  - Signals from non-primary modalities can influence neural activity in 'unimodal'
      sensory areas of the neocortex, but whether this 'extra-modal' influence has any
      relevant consequences for neural coding has been unclear. Recent findings show
      that vision enhances the information content of neural signals in auditory
      cortex, but in a counter-intuitive fashion.

PMID- 20152140
TI  - Experimental evolution: the rate of adaptive evolution.
AB  - Next-generation sequencing technology allows the identification of molecular
      changes that have arisen in the genomes of microorganisms undergoing experimental
      evolution. This permits the elucidation of the molecular evolutionary dynamics in
      these populations.

PMID- 20152141
TI  - Courtship behavior: the right touch stimulates the proper song.
AB  - Male fruit flies touch females during courtship. A new study finds that pheromone
      input received through the male's foreleg allows him to generate the courtship
      song appealing to female flies. This activity involves sexually dimorphic
      fruitless-expressing neurons in the brain.

PMID- 20152142
TI  - Adaptive radiations: competition rules for Galapagos gastropods.
AB  - New islands present the perfect opportunity for a species to get a fresh start
      and undergo adaptive radiation. For Galapagos land snails, both competition and
      resource diversity have together led to opportunity knocking twice.

PMID- 20152143
TI  - Common mechanisms of synaptic plasticity in vertebrates and invertebrates.
AB  - Until recently, the literature on learning-related synaptic plasticity in
      invertebrates has been dominated by models assuming plasticity is mediated by
      presynaptic changes, whereas the vertebrate literature has been dominated by
      models assuming it is mediated by postsynaptic changes. Here I will argue that
      this situation does not reflect a biological reality and that, in fact,
      invertebrate and vertebrate nervous systems share a common set of mechanisms of
      synaptic plasticity.

PMID- 20152144
TI  - Convergent recognition of a triple helical hydrophobic motif in collagen.

PMID- 20152145
TI  - Herpesviruses: an in-depth view.

PMID- 20152146
TI  - Molecular machines and targeted molecular dynamics: DNA in motion.

PMID- 20152147
TI  - Catching pneumonia.

PMID- 20152148
TI  - Reverse micelle encapsulation of membrane-anchored proteins for solution NMR
      studies.
AB  - Perhaps 5%-10% of proteins bind to membranes via a covalently attached lipid.
      Posttranslational attachment of fatty acids such as myristate occurs on a variety
      of viral and cellular proteins. High-resolution information about the nature of
      lipidated proteins is remarkably sparse, often because of solubility problems
      caused by the exposed fatty acids. Reverse micelle encapsulation is used here to
      study two myristoylated proteins in their lipid-extruded states: myristoylated
      recoverin, which is a switch in the Ca(2+) signaling pathway in vision, and the
      myristoylated HIV-1 matrix protein, which is postulated to be targeted to the
      plasma membrane through its binding to phosphatidylinositol-4,5-bisphosphate.
      Both proteins have been successfully encapsulated in the lipid-extruded state and
      high-resolution NMR spectra obtained. Both proteins bind their activating ligands
      in the reverse micelle. This approach seems broadly applicable to membrane
      proteins with exposed fatty acid chains that have eluded structural
      characterization by conventional approaches.

PMID- 20152149
TI  - Zernike phase plate cryoelectron microscopy facilitates single particle analysis
      of unstained asymmetric protein complexes.
AB  - Single particle reconstruction from cryoelectron microscopy images, though
      emerging as a powerful means in structural biology, is faced with challenges as
      applied to asymmetric proteins smaller than megadaltons due to low contrast.
      Zernike phase plate can improve the contrast by restoring the microscope contrast
      transfer function. Here, by exploiting simulated Zernike and conventional
      defocused cryoelectron microscope images with noise characteristics comparable to
      those of experimental data, we quantified the efficiencies of the steps in single
      particle analysis of ice-embedded RNA polymerase II (500 kDa), transferrin
      receptor complex (290 kDa), and T7 RNA polymerase lysozyme (100 kDa). Our results
      show Zernike phase plate imaging is more effective as to particle identification
      and also sorting of orientations, conformations, and compositions. Moreover, our
      analysis on image alignment indicates that Zernike phase plate can, in principle,
      reduce the number of particles required to attain near atomic resolution by 10
      100 fold for proteins between 100 kDa and 500 kDa.

PMID- 20152151
TI  - Probing the interactions of carboxy-atractyloside and atractyloside with the
      yeast mitochondrial ADP/ATP carrier.
AB  - Mitochondrial ADP/ATP carriers are inhibited by two natural compounds,
      atractyloside (ATR) or carboxy-atractyloside (CATR), which differ by one
      carboxylate group. The interactions of the inhibitors with the carrier were
      investigated by single-molecule force spectroscopy. Transmembrane alpha helices
      of the ATR-inhibited carrier displayed heterogeneous mechanical and kinetic
      properties. Whereas alpha helix H2 showed the most brittle mechanical properties
      and lowest kinetic stability, alpha helix H5 was mechanically the most flexible
      and possessed a kinetic stability 9 orders of magnitude greater than that of
      alpha helix H2. In contrast, CATR-binding substantially increased the kinetic
      stability of alpha helix H2 and tuned the mechanical flexibility of alpha helices
      H5 and H6. NMR spectroscopy confirmed that the additional carboxylate group of
      CATR binds to the sixth alpha helix, indicating that the enhanced stability of H2
      is mediated via interactions between CATR and H6.

PMID- 20152150
TI  - Crystal structure of the APOBEC3G catalytic domain reveals potential
      oligomerization interfaces.
AB  - APOBEC3G is a DNA cytidine deaminase that has antiviral activity against HIV-1
      and other pathogenic viruses. In this study the crystal structure of the
      catalytically active C-terminal domain was determined to 2.25 A. This structure
      corroborates features previously observed in nuclear magnetic resonance (NMR)
      studies, a bulge in the second beta strand and a lengthening of the second alpha
      helix. Oligomerization is postulated to be critical for the function of APOBEC3G.
      In this structure, four extensive intermolecular interfaces are observed,
      suggesting potential models for APOBEC3G oligomerization. The structural and
      functional significance of these interfaces was probed by solution NMR and
      disruptive variants were designed and tested for DNA deaminase and anti-HIV
      activities. The variant designed to disrupt the most extensive interface lost
      both activities. NMR solution data provides evidence that another interface,
      which coordinates a novel zinc site, also exists. Thus, the observed
      crystallographic interfaces of APOBEC3G may be important for both oligomerization
      and function.

PMID- 20152152
TI  - Three-dimensional visualization of gammaherpesvirus life cycle in host cells by
      electron tomography.
AB  - Gammaherpesviruses are etiologically associated with human tumors. A three
      dimensional (3D) examination of their life cycle in the host is lacking,
      significantly limiting our understanding of the structural and molecular basis of
      virus-host interactions. Here, we report the first 3D visualization of key stages
      of the murine gammaherpesvirus 68 life cycle in NIH 3T3 cells, including viral
      attachment, entry, assembly, and egress, by dual-axis electron tomography. In
      particular, we revealed the transient processes of incoming capsids injecting
      viral DNA through nuclear pore complexes and nascent DNA being packaged into
      progeny capsids in vivo as a spool coaxial with the putative portal vertex. We
      discovered that intranuclear invagination of both nuclear membranes is involved
      in nuclear egress of herpesvirus capsids. Taken together, our results provide the
      structural basis for a detailed mechanistic description of gammaherpesvirus life
      cycle and also demonstrate the advantage of electron tomography in dissecting
      complex cellular processes of viral infection.

PMID- 20152153
TI  - A TNF-like trimeric lectin domain from Burkholderia cenocepacia with specificity
      for fucosylated human histo-blood group antigens.
AB  - The opportunistic pathogen Burkholderia cenocepacia expresses several soluble
      lectins, among them BC2L-C. This lectin exhibits two domains: a C-terminal domain
      with high sequence similarity to the recently described calcium-dependent mannose
      binding lectin BC2L-A, and an N-terminal domain of 156 amino acids without
      similarity to any known protein. The recombinant N-terminal BC2L-C domain is a
      new lectin with specificity for fucosylated human histo-blood group epitopes H
      type 1, Lewis b, and Lewis Y, as determined by glycan array and isothermal
      titration calorimetry. Methylselenofucoside was used as ligand to solve the
      crystal structure of the N-terminal BC2L-C domain. Additional molecular modeling
      studies rationalized the preference for Lewis epitopes. The structure reveals a
      trimeric jellyroll arrangement with striking similarity to TNF-like proteins, and
      to BclA, the spore protein from Bacillus anthracis which may play an important
      role in bioadhesion of anthrax spores in human lungs.

PMID- 20152154
TI  - Solution structure of a unique G-quadruplex scaffold adopted by a guanosine-rich
      human intronic sequence.
AB  - We report on the solution structure of an unprecedented intramolecular G
      quadruplex formed by the guanosine-rich human chl1 intronic d(G(3)-N-G(4)-N(2)
      G(4)-N-G(3)-N) 19-mer sequence in K(+)-containing solution. This G-quadruplex,
      composed of three stacked G-tetrads containing four syn guanines, represents a
      new folding topology with two unique conformational features. The first guanosine
      is positioned within the central G-tetrad, in contrast to all previous structures
      of unimolecular G-quadruplexes, where the first guanosine is part of an outermost
      G-tetrad. In addition, a V-shaped loop, spanning three G-tetrad planes, contains
      no bridging nucleotides. The G-quadruplex scaffold is stabilized by a T*G*A
      triple stacked over the G-tetrad at one end and an unpaired guanosine stacked
      over the G-tetrad at the other end. Finally, the chl1 intronic DNA G-quadruplex
      scaffold contains a guanosine base intercalated between an extended G-G step, a
      feature observed in common with the catalytic site of group I introns. This
      unique structural scaffold provides a highly specific platform for the future
      design of ligands specifically targeted to intronic G-quadruplex platforms.

PMID- 20152155
TI  - The mechanism of the translocation step in DNA replication by DNA polymerase I: a
      computer simulation analysis.
AB  - High-fidelity DNA polymerases copy DNA rapidly and accurately by adding correct
      deoxynucleotide triphosphates to a growing primer strand of DNA. Following
      nucleotide incorporation, a series of conformational changes translocate the DNA
      substrate by one base pair step, readying the polymerase for the next round of
      incorporation. Molecular dynamics simulations indicate that the translocation
      consists globally of a polymerase fingers-opening transition, followed by the DNA
      displacement and the insertion of the template base into the preinsertion site.
      They also show that the pyrophosphate release facilitates the opening transition
      and that the universally conserved Y714 plays a key role in coupling polymerase
      opening to DNA translocation. The transition involves several metastable
      intermediates in one of which the O helix is bent in the vicinity of G711.
      Completion of the translocation appears to require a gating motion of the O1
      helix, perhaps facilitated by the presence of G715. These roles are consistent
      with the high level of conservation of Y714 and the two glycine residues at these
      positions. It is likely that a corresponding mechanism is applicable to other
      polymerases.

PMID- 20152156
TI  - Crystal structures of dehydratase domains from the curacin polyketide
      biosynthetic pathway.
AB  - Modular polyketide synthases (PKS) make novel natural products through a series
      of preprogrammed chemical steps catalyzed by an assembly line of multidomain
      modules. Each assembly-line step involves unique extension and modification
      reactions, resulting in tremendous diversity of polyketide products. Dehydratase
      domains catalyze formation of an alpha,beta-double bond in the nascent polyketide
      intermediate. We present crystal structures of the four dehydratase domains from
      the curacin A PKS. The catalytic residues and substrate binding site reside in a
      tunnel within a single monomer. The positions of the catalytic residues and shape
      of the substrate tunnel explain how chirality of the substrate hydroxyl group may
      determine the configuration of the product double bond. Access to the active site
      may require opening the substrate tunnel, forming an open trench. The arrangement
      of monomers within the dimer is consistent among PKS dehydratases and differs
      from that seen in the related mammalian fatty acid synthases.

PMID- 20152157
TI  - Structural basis of host cell recognition by the pilus adhesin from Streptococcus
      pneumoniae.
AB  - Pili are fibrous virulence factors associated directly to the bacterial surface
      that play critical roles in adhesion and recognition of host cell receptors. The
      human pathogen Streptococcus pneumoniae carries a single pilus-related adhesin
      (RrgA) that is key for infection establishment and provides protection from
      bacterial challenge in animal infection models, but details of these roles remain
      unclear. Here we report the high-resolution crystal structure of RrgA, a 893
      residue elongated macromolecule whose fold contains four domains presenting both
      eukaryotic and prokaryotic origins. RrgA harbors an integrin I collagen
      recognition domain decorated with two inserted "arms" that fold into a positively
      charged cradle, as well as three "stalk-forming" domains. We show by site
      specific mutagenesis, mass spectrometry, and thermal shift assays that
      intradomain isopeptide bonds play key roles in stabilizing RrgA's stalk. The high
      sequence similarity between RrgA and its homologs in other Gram-positive
      microorganisms suggests common strategies for ECM recognition and immune evasion.

PMID- 20152158
TI  - Conformational changes in guanylate cyclase-activating protein 1 induced by Ca2+
      and N-terminal fatty acid acylation.
AB  - Neuronal Ca(2+) sensors (NCS) are high-affinity Ca(2+)-binding proteins critical
      for regulating a vast range of physiological processes. Guanylate cyclase
      activating proteins (GCAPs) are members of the NCS family responsible for
      activating retinal guanylate cyclases (GCs) at low Ca(2+) concentrations,
      triggering synthesis of cGMP and recovery of photoreceptor cells to the dark
      adapted state. Here we use amide hydrogen-deuterium exchange and radiolytic
      labeling, and molecular dynamics simulations to study conformational changes
      induced by Ca(2+) and modulated by the N-terminal myristoyl group. Our data on
      the conformational dynamics of GCAP1 in solution suggest that Ca(2+) stabilizes
      the protein but induces relatively small changes in the domain structure;
      however, loss of Ca(+2) mediates a significant global relaxation and movement of
      N- and C-terminal domains. This model and the previously described "calcium
      myristoyl switch" proposed for recoverin indicate significant diversity in
      conformational changes among these highly homologous NCS proteins with distinct
      functions.

PMID- 20152160
TI  - Crystal structure of UbcH5b~ubiquitin intermediate: insight into the formation of
      the self-assembled E2~Ub conjugates.
AB  - E2 ubiquitin-conjugating enzymes catalyze the attachment of ubiquitin to lysine
      residues of target proteins. The UbcH5b E2 enzyme has been shown to play a key
      role in the initiation of the ubiquitination of substrate proteins upon action of
      several E3 ligases. Here we have determined the 2.2 A crystal structure of an
      intermediate of UbcH5b~ubiquitin (Ub) conjugate, which is assembled into an
      infinite spiral through the backside interaction. This active complex may provide
      multiple E2 active sites, enabling efficient ubiquitination of substrates.
      Indeed, biochemical assays support a model in which the self-assembled UbcH5b~Ub
      can serve as a bridge for the gap between the lysine residue of the substrate and
      the catalytic cysteine of E2.

PMID- 20152159
TI  - Insights from the structure of a smallpox virus topoisomerase-DNA transition
      state mimic.
AB  - Poxviruses encode their own type IB topoisomerases (TopIBs), which release
      superhelical tension generated by replication and transcription of their genomes.
      To investigate the reaction catalyzed by viral TopIBs, we have determined the
      structure of a variola virus topoisomerase-DNA complex trapped as a vanadate
      transition state mimic. The structure reveals how the viral TopIB enzymes are
      likely to position the DNA duplex for ligation following relaxation of supercoils
      and identifies the sources of friction observed in single-molecule experiments
      that argue against free rotation. The structure also identifies a conformational
      change in the leaving group sugar that must occur prior to cleavage and reveals a
      mechanism for promoting ligation following relaxation of supercoils that involves
      an Asp-minor groove interaction. Overall, the new structural data support a
      common catalytic mechanism for the TopIB superfamily but indicate distinct
      methods for controlling duplex rotation in the small versus large enzyme
      subfamilies.

PMID- 20152161
TI  - Characteristics of IL-17-producing gammadelta T cells.

PMID- 20152164
TI  - Why CD8+ T cells need diversity when growing up.
AB  - A thymus-specific subunit of the proteasome, beta5t, was previously described and
      shown to be essential for positive selection of CD8+ T cells. In this issue of
      Immunity, Nitta et al. (2010) suggest that beta5t is essential because it alters
      the specific peptide-MHC complexes displayed by cortical epithelial cells.

PMID- 20152165
TI  - Interleukin-2 tickles T cell memory.
AB  - The differentiation of peripheral T lymphocytes depends on interactions between
      intrinsic and extrinsic factors. In this issue of Immunity, Pipkin et al. (2010)
      and Kalia et al. (2010) link differential interleukin-2 signaling and
      inflammation with the transcriptional events leading to the development of
      effector and memory cells.

PMID- 20152166
TI  - An activation marker finds a function.
AB  - In this issue of Immunity, Baaten et al. (2010) describe a previously unknown
      role for CD44 in counteracting Fas-mediated apoptosis of Th1 effector cells
      during clonal expansion and allowing their entry into the memory pool.

PMID- 20152167
TI  - CD4+ T cell plasticity-Th2 cells join the crowd.
AB  - In this issue of Immunity, Hegazy et al. (2010) report that in response to
      lymphocytic choriomeningitis virus (LCMV) infection, fully differentiated virus
      specific Th2 cells can be reprogrammed into GATA-3(+)T-bet(+) cells capable of
      producing both interleukin-4 and interferon-gamma.

PMID- 20152168
TI  - Notch signaling in the immune system.
AB  - The Notch signaling pathway regulates many aspects of embryonic development, as
      well as differentiation processes and tissue homeostasis in multiple adult organ
      systems. Disregulation of Notch signaling is associated with several human
      disorders, including cancer. In the last decade, it became evident that Notch
      signaling plays important roles within the hematopoietic and immune systems.
      Notch plays an essential role in the development of embryonic hematopoietic stem
      cells and influences multiple lineage decisions of developing lymphoid and
      myeloid cells. Moreover, recent evidence suggests that Notch is an important
      modulator of T cell-mediated immune responses. In this review, we discuss Notch
      signaling in hematopoiesis, lymphocyte development, and function as well as in T
      cell acute lymphoblastic leukemia.

PMID- 20152169
TI  - Distinct melanization pathways in the mosquito Aedes aegypti.
AB  - Serine protease cascades are involved in blood coagulation and immunity. In
      arthropods, they regulate melanization, which plays an important role in immune
      defense and wound healing. However, the mechanisms underlying melanization
      pathways are not completely characterized. We found that in the mosquito Aedes
      aegypti, there are two distinct melanization activation pathways carried out by
      different modules of serine proteases and their specific inhibitors serpins.
      Immune melanization proteases (IMP-1 and IMP-2) and Serpin-1 mediate hemolymph
      prophenoloxidase cleavage and immune response against the malaria parasite.
      Tissue melanization, exemplified by the formation of melanotic tumors, is
      controlled by tissue melanization protease (CLIPB8), IMP-1, and Serpin-2. In
      addition, serine proteases CLIPB5 and CLIPB29 are involved in activation of Toll
      pathway by fungal infection or by infection-independent manner, respectively.
      Serpin-2 is implicated in the latter activation of Toll pathway. This study
      revealed the complexity underlying melanization and Toll pathway in mosquitoes.

PMID- 20152170
TI  - Defining a PARticular pathway of neural tube closure.
AB  - Mammalian neurulation is completed when the dorsolateral neural folds bend
      inwards, their tips make adhesive contacts across the midline, and the epithelia
      remodel to create a closed neural tube. Two recent papers (one by Camerer et al.
      in this issue of Developmental Cell) demonstrate a vital role for protease
      activated G protein-coupled receptor signaling in these late closure events,
      opening up new avenues for exploring the molecular basis of mammalian neural tube
      morphogenesis.

PMID- 20152171
TI  - A new dress code for MMPs: cleavage optional.
AB  - Matrix metalloproteinases are well known for their key roles in the processing of
      extracellular matrix and nonmatrix molecules. Recently, a new theme of
      proteolysis-independent roles for metalloproteinases has emerged, with a paper
      from Gonzalo et al. in this issue of Developmental Cell providing an
      illustration.

PMID- 20152172
TI  - Turning the page on epigenetic bookmarks.
AB  - Cells remember established patterns of gene expression through rounds of cell
      division despite dynamic changes in genomic chromatin structure. Two recent
      studies in Molecular Cell and Nature Medicine, broadly impacting on epigenetic
      gene regulation and disease, address how cells remember and suggest that both
      histone methyltransferases and locus specific DNA binding proteins can mark
      transcribed genes for reactivation after mitosis.

PMID- 20152173
TI  - Dcr1 tracked down.
AB  - RNAi is essential for pericentromeric heterochromatic formation in S. pombe, and
      although Dcr1, the initiator protein of this process, has been biochemically well
      described, its subcellular localization has remained elusive. In this issue of
      Developmental Cell, Emmerth et al. now show that Dcr1 is dynamically shuttling
      between nucleus and cytoplasm, adding new insight into the subcellular mechanics
      of RNAi.

PMID- 20152176
TI  - Beta1 integrin establishes endothelial cell polarity and arteriolar lumen
      formation via a Par3-dependent mechanism.
AB  - Maintenance of single-layered endothelium, squamous endothelial cell shape, and
      formation of a patent vascular lumen all require defined endothelial cell
      polarity. Loss of beta1 integrin (Itgb1) in nascent endothelium leads to
      disruption of arterial endothelial cell polarity and lumen formation. The loss of
      polarity is manifested as cuboidal-shaped endothelial cells with dysregulated
      levels and mislocalization of normally polarized cell-cell adhesion molecules, as
      well as decreased expression of the polarity gene Par3 (pard3). beta1 integrin
      and Par3 are both localized to the endothelial layer, with preferential
      expression of Par3 in arterial endothelium. Luminal occlusion is also exclusively
      noted in arteries, and is partially rescued by replacement of Par3 protein in
      beta1-deficient vessels. Combined, our findings demonstrate that beta1 integrin
      functions upstream of Par3 as part of a molecular cascade required for
      endothelial cell polarity and lumen formation.

PMID- 20152175
TI  - Local protease signaling contributes to neural tube closure in the mouse embryo.
AB  - We report an unexpected role for protease signaling in neural tube closure and
      the formation of the central nervous system. Mouse embryos lacking protease
      activated receptors 1 and 2 showed defective hindbrain and posterior neuropore
      closure and developed exencephaly and spina bifida, important human congenital
      anomalies. Par1 and Par2 were expressed in surface ectoderm, and Par2 was
      expressed selectively along the line of closure. Ablation of G(i/z) and Rac1
      function in these Par2-expressing cells disrupted neural tube closure, further
      implicating G protein-coupled receptors and identifying a likely effector
      pathway. Cluster analysis of protease and Par2 expression patterns revealed a
      group of membrane-tethered proteases often coexpressed with Par2. Among these,
      matriptase activated Par2 with picomolar potency, and hepsin and prostasin
      activated matriptase. Together, our results suggest a role for protease-activated
      receptor signaling in neural tube closure and identify a local protease network
      that may trigger Par2 signaling and monitor and regulate epithelial integrity in
      this context.

PMID- 20152174
TI  - Preparing for the first breath: genetic and cellular mechanisms in lung
      development.
AB  - The mammalian respiratory system--the trachea and the lungs--arises from the
      anterior foregut through a sequence of morphogenetic events involving reciprocal
      endodermal-mesodermal interactions. The lung itself consists of two highly
      branched, tree-like systems--the airways and the vasculature--that develop in a
      coordinated way from the primary bud stage to the generation of millions of
      alveolar gas exchange units. We are beginning to understand some of the molecular
      and cellular mechanisms that underlie critical processes such as branching
      morphogenesis, vascular development, and the differentiation of multipotent
      progenitor populations. Nevertheless, many gaps remain in our knowledge, the
      filling of which is essential for understanding respiratory disorders, congenital
      defects in human neonates, and how the disruption of morphogenetic programs early
      in lung development can lead to deficiencies that persist throughout life.

PMID- 20152177
TI  - The tight junction protein, occludin, regulates the directional migration of
      epithelial cells.
AB  - Cell polarity proteins regulate tight junction formation and directional
      migration in epithelial cells. To date, the mechanism by which these polarity
      proteins assemble at the leading edge of migrating epithelial cells remains
      unclear. We report that occludin, a transmembrane protein, is localized at the
      leading edge of migrating cells and regulates directional cell migration. During
      migration, occludin knockdown disrupted accumulation of aPKC-Par3 and PATJ at the
      leading edge, and led to a disorganized microtubule network and defective
      reorientation of the microtubule organization center (MTOC). Phosphorylation of
      occludin at tyrosine 473 residue allowed recruitment of p85 alpha to the leading
      edge via association with its C-terminal SH2 domain. Loss of occludin attenuated
      activation of PI3K, leading to disorganization of the actin cytoskeleton and
      reduced cell protrusions. Our data indicate that occludin is required for the
      leading-edge localization of polarity proteins aPKC-Par3 and PATJ and promotes
      cell protrusion by regulating membrane-localized activation of PI3K.

PMID- 20152178
TI  - Zona pellucida domain proteins remodel the apical compartment for localized cell
      shape changes.
AB  - The zona pellucida domain (ZPD) defines a conserved family of membrane-anchored
      matrix proteins that are, as yet, poorly characterized with respect to their
      functions during development. Using genetic approaches in flies, we show here
      that a set of eight ZPD proteins is required for the localized reorganization of
      embryonic epidermal cells during morphogenesis. Despite varying degrees of
      sequence conservation, these ZPD proteins exert specific and nonredundant
      functions in the remodeling of epidermal cell shape. Each one accumulates in a
      restricted subregion of the apical compartment, where it organizes local
      interactions between the membrane and the extracellular matrix. In addition, ZPD
      proteins are required to sculpture the actin-rich cell extensions and maintain
      appropriate organization of the apical compartment. These results on ZPD proteins
      therefore reveal a functional subcompartmentalization of the apical membrane and
      its role in the polarized control of epithelial cell shape during development.

PMID- 20152180
TI  - Coupling prokaryotic cell fate and division control with a bifunctional and
      oscillating oxidoreductase homolog.
AB  - NAD(H)-binding proteins play important roles in cell-cycle and developmental
      signaling in eukaryotes. We identified a bifunctional NAD(H)-binding regulator
      (KidO) that integrates cell-fate signaling with cytokinesis in the bacterium
      Caulobacter crescentus. KidO stimulates the DivJ kinase and directly acts on the
      cytokinetic tubulin, FtsZ, to tune cytokinesis with the cell cycle. At the G1-->S
      transition, DivJ concomitantly signals the ClpXP-dependent degradation of KidO
      and CtrA, a cell-cycle transcriptional regulator/DNA replication inhibitor. This
      proteolytic event directs KidO and CtrA into oscillatory cell-cycle abundance
      patterns that coordinately license replication and cytokinesis. KidO resembles
      NAD(P)H-dependent oxidoreductases, and conserved residues in the KidO NAD(H)
      binding pocket are critical for regulation of FtsZ, but not for DivJ. Since NADPH
      dependent regulation by a KidO-like oxidoreductase also occurs in humans,
      organisms from two domains of life exploit the enzymatic fold of an ancestral
      oxidoreductase potentially to coordinate cellular or developmental activities
      with the availability of the metabolic currency, NAD(P)H.

PMID- 20152179
TI  - MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling.
AB  - Cell fusion is essential for fertilization, myotube formation, and inflammation.
      Macrophages fuse under various circumstances, but the molecular signals involved
      in the distinct steps of their fusion are not fully characterized. Using null
      mice and derived cells, we show that the protease MT1-MMP is necessary for
      macrophage fusion during osteoclast and giant-cell formation in vitro and in
      vivo. Specifically, MT1-MMP is required for lamellipodia formation and for proper
      cell morphology and motility of bone marrow myeloid progenitors prior to membrane
      fusion. These functions of MT1-MMP do not depend on MT1-MMP catalytic activity or
      downstream pro-MMP-2 activation. Instead, MT1-MMP null cells show a decreased
      Rac1 activity and reduced membrane targeting of Rac1 and the adaptor protein
      p130Cas. Retroviral rescue experiments and protein binding assays delineate a
      signaling pathway in which MT1-MMP, via its cytosolic tail, contributes to
      macrophage migration and fusion by regulating Rac1 activity through an
      association with p130Cas.

PMID- 20152181
TI  - Nuclear retention of fission yeast dicer is a prerequisite for RNAi-mediated
      heterochromatin assembly.
AB  - RNaseIII ribonucleases act at the heart of RNA silencing pathways by processing
      precursor RNAs into mature microRNAs and siRNAs. In the fission yeast
      Schizosaccharomyces pombe, siRNAs are generated by the RNaseIII enzyme Dcr1 and
      are required for heterochromatin formation at centromeres. In this study, we have
      analyzed the subcellular localization of Dcr1 and found that it accumulates in
      the nucleus and is enriched at the nuclear periphery. Nuclear accumulation of
      Dcr1 depends on a short motif that impedes nuclear export promoted by the double
      stranded RNA binding domain of Dcr1. Absence of this motif renders Dcr1 mainly
      cytoplasmic and is accompanied by remarkable changes in gene expression and
      failure to assemble heterochromatin. Our findings suggest that Dicer proteins are
      shuttling proteins and that the steady-state subcellular levels can be shifted
      toward either compartment.

PMID- 20152182
TI  - CBP histone acetyltransferase activity regulates embryonic neural differentiation
      in the normal and Rubinstein-Taybi syndrome brain.
AB  - Increasing evidence indicates that epigenetic changes regulate cell genesis.
      Here, we ask about neural precursors, focusing on CREB binding protein (CBP), a
      histone acetyltransferase that, when haploinsufficient, causes Rubinstein-Taybi
      syndrome (RTS), a genetic disorder with cognitive dysfunction. We show that
      neonatal cbp(+/-) mice are behaviorally impaired, displaying perturbed
      vocalization behavior. cbp haploinsufficiency or genetic knockdown with siRNAs
      inhibited differentiation of embryonic cortical precursors into all three neural
      lineages, coincident with decreased CBP binding and histone acetylation at
      promoters of neuronal and glial genes. Inhibition of histone deacetylation
      rescued these deficits. Moreover, CBP phosphorylation by atypical protein kinase
      C zeta was necessary for histone acetylation at neural gene promoters and
      appropriate differentiation. These data support a model in which environmental
      cues regulate CBP activity and histone acetylation to control neural precursor
      competency to differentiate, and indicate that cbp haploinsufficiency disrupts
      this mechanism, thereby likely causing cognitive dysfunction in RTS.

PMID- 20152183
TI  - dFezf/Earmuff maintains the restricted developmental potential of intermediate
      neural progenitors in Drosophila.
AB  - To ensure normal development and maintenance of homeostasis, the extensive
      developmental potential of stem cells must be functionally distinguished from the
      limited developmental potential of transit amplifying cells. Yet the mechanisms
      that restrict the developmental potential of transit amplifying cells are poorly
      understood. Here we show that the evolutionarily conserved transcription factor
      dFezf/Earmuff (Erm) functions cell-autonomously to maintain the restricted
      developmental potential of the intermediate neural progenitors generated by type
      II neuroblasts in Drosophila larval brains. Although erm mutant intermediate
      neural progenitors are correctly specified and show normal apical-basal cortical
      polarity, they can dedifferentiate back into a neuroblast state, functionally
      indistinguishable from normal type II neuroblasts. Erm restricts the potential of
      intermediate neural progenitors by activating Prospero to limit proliferation and
      by antagonizing Notch signaling to prevent dedifferentiation. We conclude that
      Erm dependence functionally distinguishes intermediate neural progenitors from
      neuroblasts in the Drosophila larval brain, balancing neurogenesis with stem cell
      maintenance.

PMID- 20152184
TI  - Neuronal regulation of the spatial patterning of neurogenesis.
AB  - Precise regulation of neurogenesis is achieved in specific regions of the
      vertebrate nervous system by formation of distinct neurogenic and nonneurogenic
      zones. We have investigated how neurogenesis becomes confined to zones adjacent
      to rhombomere boundaries in the zebrafish hindbrain. The nonneurogenic zone at
      segment centers comprises a distinct progenitor population that expresses
      fibroblast growth factor (fgfr) 2, erm, sox9b, and the retinoic acid degrading
      enzyme, cyp26b1. FGF receptor activation upregulates expression of these genes
      and inhibits neurogenesis in segment centers. Cyp26 activity is a key effector
      inhibiting neuronal differentiation, suggesting antagonistic interactions with
      retinoid signaling. We identify the critical FGF ligand, fgf20a, which is
      expressed by specific neurons located in the mantle region at the center of
      segments, adjacent to the nonneurogenic zone. Fgf20a mutants have ectopic
      neurogenesis and lack the segment center progenitor population. Our findings
      reveal how signaling from neurons induces formation of a nonneurogenic zone of
      neural progenitors.

PMID- 20152186
TI  - Spatial restriction of FGF signaling by a matrix metalloprotease controls
      branching morphogenesis.
AB  - FGF signaling is a central regulator of branching morphogenesis processes, such
      as angiogenesis or the development of branched organs including lung, kidney, and
      mammary gland. The formation of the air sac during the development of the
      Drosophila tracheal system is a powerful genetic model to investigate how FGF
      signaling patterns such emerging structures. This article describes the
      characterization of the Drosophila matrix metalloprotease Mmp2 as an
      extracellular inhibitor of FGF morphogenetic function. Mmp2 expression in the
      developing air sac is controlled by the Drosophila FGF homolog Branchless and
      then participates in a negative feedback and lateral inhibition mechanism that
      defines the precise pattern of FGF signaling. The signaling function for MMPs
      described here may not be limited to branching morphogenesis processes.

PMID- 20152187
TI  - The beginning of health care reform.

PMID- 20152185
TI  - Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon
      patterning.
AB  - Proper functioning of the musculoskeletal system requires the precise integration
      of bones, muscles, and tendons. Complex morphogenetic events ensure that these
      elements are linked together in the appropriate three-dimensional configuration.
      It has been difficult, however, to tease apart the mechanisms that regulate
      tissue morphogenesis. We find that deletion of Tbx5 in forelimbs (or Tbx4 in
      hindlimbs) specifically affects muscle and tendon patterning without disrupting
      skeletal development, thus suggesting that distinct cues regulate these
      processes. We identify muscle connective tissue as the site of action of these
      transcription factors and show that N-Cadherin and beta-Catenin are key
      downstream effectors acting in muscle connective tissue and regulating soft
      tissue morphogenesis. In humans, TBX5 mutations lead to Holt-Oram syndrome, which
      is characterized by forelimb musculoskeletal defects. Our results suggest that a
      focus on connective tissue is required to understand the etiology of diseases
      affecting soft tissue formation.

PMID- 20152188
TI  - Thinking critically.

PMID- 20152190
TI  - Silence can hurt patients.

PMID- 20152189
TI  - Nursing's code of ethics.

PMID- 20152196
TI  - Chasing zero: our journey to preventing surgical site infection.
AB  - After an increase in methicillin-resistant Staphylococcus aureus infections was
      discovered at a health care facility in Arizona, a multidisciplinary team
      convened to investigate the underlying problem and work toward eliminating
      surgical site infections. The team investigated environmental factors, held
      inservice sessions to reinforce sterile technique, and made important changes to
      the facility culture in efforts to eliminate surgical site infections. The team's
      efforts were put into practice on October 30, 2008, and only one surgical site
      infection was identified in the following seven months.

PMID- 20152197
TI  - The validation of AORN recommended practices in Finnish perioperative nursing
      documentation.
AB  - In Finland, there are no common guidelines or recommended practices for
      perioperative documentation. Thus, perioperative nursing documentation varies
      from one operating department to another. To create minimum criteria for nursing
      documentation in Finland, we conducted an investigation in a university hospital
      district in 2006. Purposive sampling was used to invite experts in perioperative
      nursing documentation (N = 42) to serve as a Delphi panel. The final criteria are
      120 items, 71% of which are based on the AORN standards and recommended
      practices. These criteria may be used to educate students and new perioperative
      personnel and to enhance the quality of nursing practice. To ensure relevance and
      usability, the criteria should be tested in various perioperative settings with a
      variety of surgical patients.

PMID- 20152198
TI  - Developing critical thinking in the perioperative environment.
AB  - Critical thinking is considered an essential skill for nurses by many, including
      major accrediting agencies, health care administrators, and AORN. This is in part
      because of the environment in which nurses function. Health care, medicine,
      technology, and nursing are dynamic and constantly changing. The perioperative
      environment is complex, fast paced, unique, and oftentimes unpredictable.
      Critical thinking skills enable perioperative nurses to function effectively and
      evolve in this ever-changing environment. Nursing education programs are mandated
      to teach critical thinking skills. It is the practice arena, however, that
      refines, hones, and grows these skills. This article provides an overview of
      critical thinking in the context of nursing, as well as strategies and
      interventions designed to teach critical thinking skills.

PMID- 20152199
TI  - Steps for successful implementation of proteomic research in the OR.
AB  - Proteomic studies (ie, the investigation and identification of proteins found in
      biological samples such as blood and tissue) are at the forefront of the
      identification of disease biomarkers and the understanding of proteins. These
      studies promise to enhance diagnostic and prognostic analysis across all
      disciplines of clinical practice. As the practice of nursing and medicine becomes
      more preventative in nature and predictive in terms of patient care, successfully
      integrating and implementing proteomic research will become increasingly
      important, especially in the OR. It is imperative that perioperative nurses and
      researchers establish a collaborative process for specimen collection. Steps in
      establishing and maintaining a successful specimen collection program include
      implementing and evaluating a protocol, developing good communication, and
      keeping all participants up to date on the progress of the study.

PMID- 20152200
TI  - Surgical vacuum drains: types, uses, and complications.
AB  - High- and low-pressure vacuum drains are commonly used after surgical procedures.
      High-pressure vacuum drains (ie, sealed, closed-circuit systems) are efficient
      and allow for easy monitoring and safe disposal of the drainage. Low-pressure
      vacuum drains use gentle pressure to evacuate excess fluid and air, and are easy
      for patients to manage at home because it is easy to reinstate the vacuum
      pressure. Perioperative nurses should be able to identify the various types of
      commonly used drains and their surgical applications. Nurses should know how to
      care for drains, how to reinstate the vacuum pressure when necessary, and the
      potential complications that could result from surgical drain use.

PMID- 20152201
TI  - Managing a chest tube and drainage system.
AB  - Intercostal drainage tubes (ie, chest tubes) are inserted to drain the pleural
      cavity of air, blood, pus, or lymph. The water-seal container connected to the
      chest tube allows one-way movement of air and liquid from the pleural cavity. The
      container should not be changed unless it is full, and the chest tube should not
      be clamped unnecessarily. After a chest tube is inserted, a nurse trained in
      chest-tube management is responsible for managing the chest tube and drainage
      system. This entails monitoring the chest-tube position, controlling fluid
      evacuation, identifying when to change or empty the containers, and caring for
      the tube and drainage system during patient transport. This article provides an
      overview of indications, insertion techniques, and management of chest tubes.

PMID- 20152202
TI  - To err is human, to drift is normalization of deviance.

PMID- 20152204
TI  - Magnet recognition: examples of perioperative excellence.

PMID- 20152206
TI  - Staggered sensitivity results.

PMID- 20152207
TI  - ST-elevation myocardial infarction patients can be enrolled in randomized trials
      before emergent coronary intervention without sacrificing door-to-balloon time.

PMID- 20152208
TI  - Electrocardiographic predictors of atrial fibrillation: methodological
      considerations.

PMID- 20152210
TI  - Nephrotoxicity of iodixanol versus iopamidol inpatients with chronic kidney
      disease and diabetes mellitus undergoing coronary angiographic procedures.

PMID- 20152212
TI  - Effectiveness and safety of drug-eluting stents in vein grafts: a meta-analysis.
AB  - BACKGROUND: The use of drug-eluting stents (DES) in degenerative vein grafts is
      currently an off-label indication. Recent studies have had conflicting results
      regarding the effectiveness and safety of this practice. The objective of this
      meta-analysis was to compare DES to bare-metal stents for the treatment of vein
      graft stenosis. METHODS: PubMed and the Cochrane clinical trials database were
      systematically searched to identify all randomized controlled trials (RCTs) and
      observational studies examining DES for vein graft stenosis published in English
      between 2003 and 2009. Inclusion criteria included follow-up duration > or =6
      months. Data were stratified by study design and pooled using random effects
      models. RESULTS: Twenty studies were found to meet our inclusion criteria.
      Eighteen studies were observational and 2 were RCTs. In observational studies,
      DES were associated with a reduction in major adverse cardiac events (MACE) (odds
      ratio [OR] 0.50, 95% CI 0.35-0.72), death (OR 0.69, 95% CI 0.53-0.91), target
      vessel revascularization (TVR) (OR 0.54, 95% CI 0.37-0.79), and target lesion
      revascularization (TLR) (OR 0.54, 95% CI 0.37-0.78). The incidence of myocardial
      infarction was similar between groups. In the RCTs, pooled results were
      inconclusive because of small sample sizes. CONCLUSIONS: Although data from
      observational studies suggest that the use of DES for vein graft stenosis has
      favorable effects on MACE, death, TVR, and TLR, these data should be interpreted
      with caution due to their observational nature. Corresponding RCT data are
      inconclusive. There remains a need for large multicenter RCTs to address the
      effectiveness and safety of DES for vein graft stenosis.

PMID- 20152213
TI  - Cardiac deatH prevention by aUtomated defibrillatoRs in ChurcHes: rationale and
      design of the CHURCH trial.
AB  - Early defibrillation programs by the use of automated external defibrillators
      (AEDs) located in high-attendance public places may improve survival and
      neurologic outcome of patients undergoing sudden cardiac arrest (SCA). We planned
      a prospective cohort study to assess the effectiveness of a public-access
      defibrillation program based on positioning of AEDs in churches and training of
      lay volunteers in Basic Life Support Defibrillation during a single-day 5-hour
      training session. The CHURCH project aims to promote a widespread diffusion of
      AEDs, to train a large number of lay volunteers in Basic Life Support
      Defibrillation, and to increase population awareness on the opportunities for
      sudden death prevention. The rationale of the study rests on a survey
      commissioned by the Diocese of Milan that found a high prevalence of elderly
      subjects (44.5% were >60 years old) attending holy services in the morning hours,
      when sudden death incidence peaks. The catchment areas of the 12 parishes
      included in the trial as of June 2008 include a population of 140,000. The
      projected incidence of AED-treatable SCA, based on the presence of trained
      volunteers in the churches during day hours, at the CHURCH participating sites
      was estimated at 8 episodes per year. To estimate an overall 30% mortality
      reduction from SCA after AED placement at the study sites with respect to
      conventional SCA management by the Emergency Medical Service, 25 SCA episodes
      will have to be treated during the 4-year study period. The CHURCH project might
      be of interest and applicable in every country where high-attendance worship
      places are present.

PMID- 20152214
TI  - Randomized comparison between clinical evaluation plus N-terminal pro-B-type
      natriuretic peptide versus exercise testing for decision making in acute chest
      pain of uncertain origin.
AB  - BACKGROUND: Exercise testing constitutes the usual tool for decision making in
      chest pain units. This policy implies logistical constrains. Our aim was to
      evaluate a new strategy, combining a clinical risk score and N-terminal pro-B
      type natriuretic peptide (NT-proBNP), in patients presenting to the emergency
      department with chest pain, without ischemic electrocardiogram changes or
      troponin elevation. METHODS: A total of 320 patients were randomized to either
      usual management, involving exercise testing, or a new strategy combining a
      clinical risk score and NT-proBNP without exercise testing. In the usual
      management, discharge decision was guided by the result of exercise test. In the
      new strategy, those patients with low clinical risk score and NT-proBNP were
      directly discharged. The primary outcome was hospitalization at the index
      episode. Secondary outcomes were cardiac events at 1 year. RESULTS: A total of
      110 patients (69%) were hospitalized using usual management in comparison with 90
      (56%) in the new strategy (P = .03). There were no differences in death or
      myocardial infarction (n = 11, 6.9% vs n = 6, 3.8%, P = .3) or cardiac events (n
      = 38, 24% vs n = 28, 18%, P = .2). Revascularizations at the index episode were
      more frequent under usual management (18% vs 8%, P = .01), although the new
      strategy was associated with higher rate of planned postdischarge
      revascularizations (0.6% vs 5%, P = .04). CONCLUSIONS: A strategy combining
      clinical history and NT-proBNP is simpler and reduced initial emergency
      hospitalizations in patients with chest pain, in comparison with the usual
      strategy involving exercise testing. Larger studies to assess its impact on long
      term hard end points are needed.

PMID- 20152215
TI  - Primary care practices and determinants of optimal anticoagulation management in
      a collaborative care model.
AB  - BACKGROUND: In a collaborative care model (CCM) for managing oral anticoagulant
      therapy, patients are followed at a pharmacist-managed anticoagulation service
      and, once stabilized, are transferred to their primary care physician. The
      objective of this study was to describe physicians' clinical practices and the
      practice characteristics associated with better international normalized ratio
      (INR) control in a CCM. METHODS: A telephone questionnaire about their practices
      was administered to 121 physicians exposed to a CCM. The physicians followed 121
      patients for a mean of 14.5 weeks. The percentage of time within the exact INR
      target range was computed and dichotomized (> or = or < median time within target
      range). Determinants of better INR control were identified using logistic
      regression models. RESULTS: The survey revealed that, after discharge from the
      pharmacist-managed anticoagulation service, patients are followed mainly by
      physicians and their secretaries. Physicians do not often consult other health
      professionals. Few report using technological resources to obtain INR results
      (39.7%), document medical follow-up (6.6%), or detect drug (32.2%) and food
      (9.9%) interactions. The median percentage of time within the exact INR target
      range was 84%. Determinants of better INR control include using computerized
      support to monitor patients (odds ratio [OR] 9.16, 95% CI 1.77-47.4) and detect
      drug interactions (OR 3.49, 95% CI 1.71-7.10) and consulting specialists (OR
      5.92, 95% CI 1.49-32.48). CONCLUSIONS: Primary care physicians are poorly
      supported by technological and human resources to monitor patients on oral
      anticoagulant. Even in a CCM, interprofessional collaboration and better
      technological support may be associated with optimal INR control.

PMID- 20152216
TI  - Routine use of fondaparinux in acute coronary syndromes: a 2-year multicenter
      experience.
AB  - BACKGROUND: Fondaparinux has recently been approved in patients with acute
      coronary syndromes. The primary aim of this study was to describe the changes in
      use of anticoagulants between January 2006 and December 2007. The secondary aim
      was to compare 30-day mortality and rate of a combined end point (30-day death or
      major bleeding) according to the initial and final anticoagulant agent used.
      METHODS: The rates of use of unfractionated heparin (UFH), enoxaparin, and
      fondaparinux were compared by periods of 1 month in a multicenter registry. The
      initial anticoagulant (first used at admission), the final anticoagulant (last
      used during hospitalization), and switches in anticoagulation were recorded.
      Temporal trends in monthly use of each anticoagulant were assessed; 30-day
      mortality rates and the combined end point were compared according to initial and
      final anticoagulant. RESULTS: Among 2,874 patients included, the first
      anticoagulant used was UFH in 26%, enoxaparin in 59%, and fondaparinux in 15%.
      Respective figures for final anticoagulant were 17%, 56%, and 27%. Although 3
      centers did not use fondaparinux (community centers with catheterization
      laboratory), the overall rate of use of fondaparinux, as initial and final
      anticoagulant, increased at the expense of the use of enoxaparin. We observed a
      growing proportion of patients with a switch from UFH to either enoxaparin or
      fondaparinux, ranging from 5% at the beginning to 25% at the end of the study.
      Patients treated with UFH were older, had more comorbidities, were at higher
      risk, and received fewer guidelines-recommended treatments. In patients submitted
      to angioplasty and treated with fondaparinux, a bolus of 60 IU/kg of UFH was
      added. After adjustment, 30-day mortality and combined end point rates were
      higher in patients treated with UFH. Irrespective of the type of acute coronary
      syndromes, patients treated with enoxaparin or fondaparinux had similar outcomes.
      CONCLUSIONS: Between 2006 and 2007, the use of fondaparinux in patients with
      acute coronary syndromes increased considerably, either because it was used
      instead of enoxaparin or because of a switch from UFH. Adjusted mortality in
      patients treated with fondaparinux was lower than with UFH and similar to
      enoxaparin.

PMID- 20152218
TI  - Are quality improvements associated with the Get With the Guidelines-Coronary
      Artery Disease (GWTG-CAD) program sustained over time? A longitudinal comparison
      of GWTG-CAD hospitals versus non-GWTG-CAD hospitals.
AB  - BACKGROUND: Previous reports have demonstrated that participation in GWTG-CAD, a
      national quality initiative of the American Heart Association, is associated with
      improved guideline adherence for patients hospitalized with CAD. We sought to
      establish whether these benefits from participation in GWTG-CAD were sustained
      over time. METHODS: We used the Centers for Medicare and Medicaid Services
      Hospital Compare database to examine 6 performance measures and one composite
      score for 3 consecutive 12-month periods including aspirin and beta-blocker on
      arrival/discharge, angiotensin-converting enzyme inhibitor (ACE-I) for left
      ventricular systolic dysfunction (LVSD), and adult smoking cessation counseling.
      The differences in guideline adherence between the GWTG-CAD hospitals (n = 440,
      439, 429) and non-GWTG-CAD hospitals (n = 2,438, 2,268, 2,140) were evaluated for
      each 12-month period. A multivariate mixed-effects model was used to estimate the
      independent effect of GWTG-CAD over time adjusting for hospital characteristics.
      RESULTS: Compared with non-GWTG hospitals, the GWTG-CAD hospitals demonstrated
      higher guideline adherence for 6 performance measures. The largest differences
      existed for (1) aspirin at arrival (2.3%, 2.1%, and 1.6% for each 12-month
      period, respectively), (2) aspirin at discharge (3.4%, 2.2%, and 2.3%), (3) beta
      blocker at arrival (3.4%, 2.9%, and 2.6%), and (4) beta-blocker at discharge
      (2.8%, 1.8%, and 1.5%). In multivariate analysis, the GWTG-CAD hospitals were
      independently associated with better adherence for 4 of the 6 measures (the
      exceptions were ACE-I for LVSD and smoking cessation counseling). Superior
      performance was also found for the composite measures. Although there was some
      narrowing between groups, GWTG-CAD hospitals maintained superior guideline
      adherence than non-GWTG-CAD hospitals for the entire 3-year period (adjusted
      differences 1.8%, 1.6%, and 1.4%). CONCLUSIONS: Hospitals participating in GWTG
      CAD had modestly superior acute cardiac care and secondary prevention measures
      performance relative to non-GWTG-CAD. These benefits of GWTG-CAD participation
      were sustained over time and independent of hospital characteristics.

PMID- 20152217
TI  - Anger expression and risk of coronary heart disease: evidence from the Nova
      Scotia Health Survey.
AB  - BACKGROUND: Whereas some studies have found that anger increases the risk of
      incident coronary heart disease (CHD), others found anger to be protective. Prior
      studies did not account for different types of anger expression, which may be
      associated with opposing levels of cardiovascular risk. This study examines
      whether distinct types of anger expression differentially predict incident CHD.
      METHODS: We conducted a population-based, observational prospective study of 785
      randomly selected Canadian men and women (50% each) aged 46 to 92 years and free
      of CHD in 1995. Using videotaped interviews, trained coders rated 3 types of
      anger expression: constructive anger (discussing anger to resolve the situation),
      destructive anger justification (blaming others for one's anger), and destructive
      anger rumination (brooding over an anger-inducing incident). The association
      between anger expression type per SD and incident CHD was estimated using Cox
      proportional hazards models adjusted for sex, age, cardiovascular risk factors,
      depressive symptoms, hostility, and anxiety. Interactions of anger expression
      type and gender were also tested. RESULTS: There were 115 incident CHD events
      (14.6%) during 6,584 person-years of follow-up. The association between
      clinically assessed constructive anger expression and CHD varied by gender (P for
      interaction = .02); higher levels were associated with a lower risk of incident
      CHD in men only (hazard ratio 0.58, 95% CI 0.43-0.80, P < .001), whereas higher
      levels of destructive anger justification was associated with a 31% increased
      risk of CHD in both sexes (hazard ratio 1.31, 95% CI 1.03-1.67, P = .03) and
      predicted CHD incidence independent of covariates and depressive symptoms,
      hostility, and anxiety. CONCLUSIONS: Decreased constructive anger in men and
      increased destructive anger justification in men and women are associated with
      increased risk of 10-year incident CHD.

PMID- 20152219
TI  - Parity and risk of later-life maternal cardiovascular disease.
AB  - BACKGROUND: Prior studies relating parity with maternal cardiovascular disease
      (CVD) have been performed in relatively small study samples without accounting
      for pregnancy-related complications associated with CVD. METHODS: We examined the
      associations between parity and maternal risk of later-life CVD in a population
      based cohort study using data from the Swedish population registers. Women born
      from 1932 to 1955 were followed until the occurrence of CVD, death, emigration,
      or end of follow-up (December 31, 2005). Cox proportional hazards models were
      used to estimate associations between parity and risk of CVD accounting for birth
      year, yearly income, education level, country of birth, hypertension
      (pregestational hypertension or gestational hypertension, with or without
      proteinuria), diabetes (type 1, type 2, or gestational diabetes), preterm birth,
      small for gestational age, and stillbirth. RESULTS: During a median follow-up
      time of 9.5 years (range 0-23.5), there were 65,204 CVD events in the full sample
      of women. Among 1,332,062 women, parity was associated with CVD in a J-shaped
      fashion, with 2 births representing the nadir of risk (global P value < .0001).
      Upon accounting for pregnancy-related complications in a subset of women with at
      least 1 childbirth after 1973 (n = 590,725), the association of parity with CVD
      was similar. Compared with women with 2 childbirths, the multivariable-adjusted
      hazard ratios (95% CIs) for women with 1 and >/=5 births were 1.09 (1.03-1.15)
      and 1.47 (1.37-1.57), respectively. CONCLUSIONS: In conclusion, parity was
      associated with incident maternal CVD in a J-shaped fashion, even after
      accounting for socioeconomic factors and pregnancy-related complications.

PMID- 20152220
TI  - Does aspirin use adversely influence intermediate-term postdischarge outcomes for
      hospitalized patients who are treated with angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers? Findings from Organized Program to
      Facilitate Life-Saving Treatment in Hospitalized Patients with Heart Failure
      (OPTIMIZE-HF).
AB  - BACKGROUND: Conflicting data exist regarding a potential deleterious association
      between aspirin (ASA) and angiotensin-converting enzyme inhibitors (ACEIs) when
      used concurrently in patients with heart failure (HF). How such an interaction
      may be influenced by underlying etiology of HF and whether it extends to patients
      treated with angiotensin receptor blockers (ARBs), however, are not known.
      METHODS: Eligible patients from the OPTIMIZE-HF registry were dichotomized into
      those with ischemic or nonischemic HF. Potential associations between ASA and
      ACEI or ARB use and 60- to 90-day postdischarge outcomes were assessed using Cox
      proportional and logistic regression modeling. Models were adjusted for factors
      known to influence the outcome of interest and by propensity score for ACEI or
      ARB prescription after an index HF admission. RESULTS: Mortality was not
      increased (hazard ratio [95% CI]) when ASA was used in conjunction with ACEI
      (0.51 [0.29-0.87]) or ARB (0.29 [0.09-0.96]) in patients with ischemic or
      nonischemic (ACEI 0.71 [0.42-1.21], ARB 1.42 [0.74-2.74]) HF. Regression model
      parameter estimates trended toward harm reduction, but interaction terms for
      mortality and a composite of mortality or rehospitalization were nonsignificant
      (P for all >.05). CONCLUSIONS: When combined with ACEI or ARB, ASA had no
      demonstrable adverse effect on intermediate-term postdischarge outcomes for
      patients with ischemic or nonischemic HF.

PMID- 20152221
TI  - Mechanisms of the association between depressive symptoms and long-term mortality
      in heart failure.
AB  - BACKGROUND: The long-term prognostic influence of depression on patients
      hospitalized for heart failure (HF) is unknown. No previous study has examined
      systematically the mechanisms of the relationship between depression and
      mortality in HF. METHODS: Prospective study of 433 patients hospitalized for HF
      related emergencies in 4 Spanish hospitals. Baseline depressive symptoms were
      assessed with the 10-item Geriatric Depression Scale (GDS). The association
      between depressive symptoms and mortality was summarized with hazard ratios (HRs)
      obtained from Cox regression, with sequential adjustment for possible mechanisms
      of the association. RESULTS: Of the 433 study participants, 103 (23.8%) had major
      depression (GDS-10 > or =5) at baseline. During a mean follow-up of 5.7 years,
      305 deaths (70%) occurred. Compared with those who were not depressed, subjects
      with major depression showed higher mortality (age and sex-adjusted HR 1.52, 95%
      CI 1.15-2.01). Subsequent adjustment for comorbidity reduced the HR to 1.45 (95%
      CI 1.10-1.93). Additional adjustment for severity of cardiac lesion and for
      lifestyles, foremost physical inactivity, led to a HR of 1.27 (95% CI 0.95-1.70).
      After further adjustment for pharmacologic treatment of HF and particularly for
      disability in instrumental activities of daily living, the HR dropped almost to
      the null value (HR 1.10, 95% CI 0.82-1.49). CONCLUSIONS: Depressive symptoms in
      patients hospitalized for HF are associated with higher long-term mortality; this
      association is largely explained by the frequent comorbidity, physical
      inactivity, and disability of these patients.

PMID- 20152222
TI  - Influence of dedicated heart failure clinics on delivery of recommended therapies
      in outpatient cardiology practices: findings from the Registry to Improve the Use
      of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF).
AB  - BACKGROUND: National guidelines recommend heart failure (HF) disease management
      programs to facilitate adherence to evidence-based practices. This study examined
      the influence of dedicated HF clinics on delivery of guideline-recommended
      therapies for cardiology practice outpatients with HF and reduced left
      ventricular ejection fraction. METHODS: IMPROVE HF, a prospective cohort study,
      enrolled 167 cardiology practices to characterize outpatient management of 15,381
      patients with chronic systolic HF. Adherence to guideline-recommended HF
      therapies was recorded, and the presence of a dedicated HF clinic was assessed by
      survey. Multivariate models identified contributions to delivery of guideline
      recommended HF therapies. RESULTS: Of practices, 41.3% had a dedicated HF clinic.
      Practices with a dedicated HF clinic had greater adherence to 3 of 7 guideline
      recommended HF therapy measures: angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker (P = .02), beta-blocker (P = .025), and HF
      education (P = .009). After adjustment, use of a dedicated HF clinic was
      associated with greater conformity in 2 of 7 measures: cardiac resynchronization
      therapy (P = .036) and HF education (P = .005) but not angiotensin-converting
      enzyme inhibitor/angiotensin receptor blocker, beta-blocker, aldosterone
      antagonist, implantable cardioverter-defibrillator therapy, and anticoagulation
      for atrial fibrillation. CONCLUSIONS: Use of dedicated HF clinics varied in
      cardiology outpatient practices and was associated with greater use of cardiac
      resynchronization therapy and HF education but not other guideline-recommended
      therapies.

PMID- 20152223
TI  - Systematic review of trials using vasodilators in pulmonary arterial
      hypertension: why a new approach is needed.
AB  - BACKGROUND: In a previous meta-analysis on the approved treatments for pulmonary
      hypertension, we reported that all therapies caused small changes in 6-minute
      walk distance over a short period, with minimal effects on hemodynamics and no
      effect on survival. Since that last review, 10 new clinical trials with about
      1,500 patients have been published, which has increased the statistical power of
      our observations. METHODS: A systematic review of all clinical trials in
      pulmonary arterial hypertension was done. RESULTS: The pooled effect of all
      treatments strategies (relative risk [95% CI], P) now shows a significant
      reduction of 39% (2%-62%, P = .041) in all-cause mortality. The benefits were
      confined only to patients with advanced disease for 16 weeks, regardless of which
      class of drug is used. When considering the effects within each drug family, no
      class of drug produced a statistically significant reduction in all-cause
      mortality. The improved survival bore no relationship with the change in 6-minute
      walk, the primary end point in most of the trials. CONCLUSIONS: The impact of
      vasodilators on long-term survival in pulmonary arterial hypertension remains
      uncertain. Future trials need to (a) adopt new trial designs that can better
      address clinical benefits, (b) use new end points that incorporate our best
      understanding of the disease rather than the ones that are easy to administer,
      and (c) include longer durations of study and other strategies to clarify if
      survival is affected.

PMID- 20152224
TI  - Myocardial infarction and incidence of type 2 diabetes mellitus. Is admission
      blood glucose an independent predictor for future type 2 diabetes mellitus?
AB  - BACKGROUND: Although blood glucose levels in patients with acute myocardial
      infarction (AMI) are frequently elevated, studies investigating the future risk
      of type 2 diabetes mellitus (T2DM) in patients with AMI are scarce. We sought to
      investigate whether increased blood glucose levels on admission in nondiabetic
      patients with first AMI are predictive for future T2DM. METHODS: We used the KORA
      MI register database in Augsburg, Germany, and included 1,239 nondiabetic
      patients aged 25 to 74 years who were admitted to hospital between 1998 and 2003
      with a diagnosis of a first AMI and who had survived at least 28 days. Incident
      cases of T2DM and the date of diagnosis were validated by hospital records or by
      contacting the patient's treating physician. RESULTS: A total of 108 cases of
      incident T2DM were registered during a mean follow-up of 4.7 years. Cox
      proportional hazards regression analysis was done, and admission blood glucose
      was divided into quartiles (Q). Compared to AMI patients with blood glucose on
      admission <111 mg/dL (Q1), patients with levels > or =153 mg/dL (Q4) showed an
      age and sex-adjusted relative risk of 2.76 (95% CI 1.61-4.75) for incident T2DM.
      This association was only slightly attenuated after multivariable adjustment
      (hazard ratio 2.59, 95% CI 1.49-4.49). CONCLUSIONS: Admission blood glucose in
      nondiabetic AMI patients could offer an initial screening tool during the short
      term event to select those patients with high risk for future T2DM requiring a
      close monitoring of glucose metabolism.

PMID- 20152225
TI  - Biventricular pacing improves cardiac function and prevents further left atrial
      remodeling in patients with symptomatic atrial fibrillation after
      atrioventricular node ablation.
AB  - BACKGROUND: Randomized trials have demonstrated benefits of biventricular (BiV)
      pacing in patients with advanced heart failure, intraventricular conduction
      delay, and atrial fibrillation (AF) post-atrioventricular (AV) node ablation. The
      AV Node Ablation with CLS and CRT Pacing Therapies for Treatment of AF trial
      (AVAIL CLS/CRT) was designed to demonstrate superiority of BiV pacing in patients
      with AF after AV node ablation, to evaluate its effects on cardiac structure and
      function, and to investigate additional benefits of Closed Loop Stimulation (CLS)
      (BIOTRONIK, Berlin, Germany). METHODS: Patients with refractory AF underwent AV
      node ablation and were randomized (2:2:1) to BiV pacing with CLS, BiV pacing with
      accelerometer, or right ventricular (RV) pacing. Echocardiography was performed
      at baseline and 6 months, with paired data available for 108 patients. RESULTS:
      The RV pacing contributed to significant increase in left atrial volume, left
      ventricular (LV) end-systolic volume, and LV mass compared to BiV pacing.
      Ejection fraction decreased insignificantly with RV pacing compared to
      significant increase with BiV pacing. Interventricular dyssynchrony significantly
      decreased with BiV compared with RV pacing. Closed Loop Stimulation did not
      result in additional echocardiographic changes; heart rate distribution was
      significantly wider with CLS. All groups showed significant improvement in 6
      minute walk distance, quality-of-life score, and New York Heart Association
      class. CONCLUSION: In conclusion, RV pacing results in significant increase in
      left atrial volume, LV mass, and worsening of LV contractility compared to
      patients receiving BiV pacing post-AV node ablation for refractory AF. Closed
      Loop Stimulation was not associated with additional structural changes but
      resulted in significantly wider heart rate distribution.

PMID- 20152226
TI  - Analysis of the long-term effects of drug-eluting stents on coronary arterial
      wall morphology as assessed by virtual histology intravascular ultrasound.
AB  - BACKGROUND: Animal models show impairment of arterial healing after drug-eluting
      stents (DES) compared with bare-metal stents (BMS). Virtual histology
      intravascular ultrasound (VH-IVUS) offers an opportunity to assess lesion
      morphology in vivo. METHODS: We used VH-IVUS in 80 patients to assess long-term
      (median = 10 months) native artery vascular responses after 76 implantations of
      DES compared with 32 BMS. The presence of "necrotic core abutting the lumen" was
      evaluated at baseline and follow-up. RESULTS: At baseline, necrotic core abutting
      the lumen through the stent struts was observed in 76% of DES and 75% of BMS.
      Although the percentage of necrotic core within the plaque behind the stents did
      not change during follow-up in DES (23% [18%, 28%] to 22% [17%, 27%], P = .57) or
      BMS (22% [19%, 27%] to 20% [12%, 26%], P = .29), necrotic core abutting the lumen
      through the stent struts decreased more in BMS (75% to 19%, P < .001) than DES
      (76% to 61%, P = .036) because of the lack of an overlying, protective neointima
      in DES-treated lesions. Furthermore, within the adjacent reference segments, the
      incidence of necrotic core abutting the lumen decreased in BMS-treated lesions
      (proximal 23% to 0%, P = .023; distal 21% to 0%, P = .023), but not in DES
      (proximal 22% to 17%, P = .48; distal 23% to 21%, P = .82). CONCLUSIONS: Serial
      VH-IVUS analysis of DES-treated lesions showed a greater frequency of unstable
      lesion morphometry at follow-up compared with BMS. The apparent mechanism was a
      suppression of the protective neointimal hyperplasia layer coupled with a lack of
      vulnerable plaque resolution at reference segments in DES compared with BMS.

PMID- 20152227
TI  - Intracoronary thrombus formation after drug-eluting stents implantation: optical
      coherence tomographic study.
AB  - BACKGROUND: Intracoronary thrombus formation after drug-eluting stent (DES)
      implantation is not sufficiently evaluated. METHODS: Optical coherence tomography
      (OCT) was performed in 226 patients (total DES n = 244, sirolimus-eluting stent
      [SES] n = 95, paclitaxel-eluting stent [PES] n = 62, zotarolimus-eluting stent
      [ZES] n = 87) after implantation (mean 11 months, range 3-66 months). Using OCT,
      we investigated the incidence and determinants of intracoronary thrombus.
      RESULTS: Intracoronary thrombus was detected in 35 (14%) cases (27 SES [28%], 7
      PES [11%], and 1 ZES [1%], P < .001) and was associated with longer stent,
      smaller stent diameter, and stents at bifurcation lesions. More uncovered stent
      struts (26 +/- 23 vs 8 +/- 17, P < .001) and malapposed stent struts (6 +/- 14 vs
      2 +/- 6, P < .001) were also associated with intracoronary thrombus. Multiple
      logistic regression analysis found the following determinants of intracoronary
      thrombus: stent length > or =28 mm (odds ratio [OR] 7.31, 95% CI 1.79-29.86, P =
      .01), stent diameter <3.0 mm (OR 4.38, 95% CI 1.38-13.97, P = .01), and > or =8
      uncovered struts in each stent (OR 3.29, 95% CI 1.07-10.17, P = .04).
      CONCLUSIONS: Length, size, and types of DES may be more important than clinical
      factors in intracoronary thrombus formation after DES implantations.

PMID- 20152228
TI  - Triple antiplatelet therapy reduces ischemic events after drug-eluting stent
      implantation: Drug-Eluting stenting followed by Cilostazol treatment REduces
      Adverse Serious cardiac Events (DECREASE registry).
AB  - BACKGROUND: Cilostazol has reduced restenosis and repeat intervention after drug
      eluting stent (DES) implantation. However, there is little data regarding impact
      of cilostazol on cardiac events after DES implantation. Therefore, we assessed
      the long-term efficacy and safety of cilostazol in patients undergoing successful
      DES implantation. METHODS: The patients (n = 3,099) undergoing successful DES
      implantation were treated with triple (aspirin, clopidogrel, and cilostazol;
      triple group, n = 1,443) or dual (aspirin and clopidogrel; dual group, n = 1,656)
      antiplatelet therapy. We compared adverse outcomes (death, myocardial infarction
      [MI], or stent thrombosis) at 12 months using the inverse probability of
      treatment weighted (IPTW) for the entire cohort and propensity score matching.
      RESULTS: After IPTW adjustment, 12-month death (hazard ratio [HR] 0.762, 95% CI
      0.401-1.448, P = .4062) was not different between the 2 groups. However, 12-month
      MI (HR 0.233, 95% CI 0.077-0.703, P = .0097) and stent thrombosis (HR 0.136, 95%
      CI 0.035-0.521, P = .0036) were significantly lower in triple group with no
      difference of major bleeding (HR 0.969, 95% CI 0.443-2.119, P = .9372). In the
      propensity score-matched cohort (965 pairs), 12-month clinical outcomes were
      similar to those of IPTW adjustment. On extended Cox model, duration of triple
      antiplatelet therapy was associated with reduction of stent thrombosis (HR 0.056,
      95% CI 0.003-0.916, P = .0433) and MI (HR 0.749, 95% CI 0.568-0.988, P = .0408).
      CONCLUSIONS: Triple antiplatelet therapy significantly reduced 12-month risks of
      stent thrombosis and MI after DES implantation compared with dual antiplatelet
      therapy without increased risk of bleeding complications. The longer duration of
      triple therapy after DES implantation was associated with the lower risk of stent
      thrombosis and MI.

PMID- 20152229
TI  - The effect of obesity on quality of life in patients with diabetes and coronary
      artery disease.
AB  - BACKGROUND: Obesity increases the risk of type 2 diabetes and coronary artery
      disease (CAD). Because all 3 conditions may reduce quality of life, the extent to
      which obesity, diabetes, and CAD independently affect quality of life is
      uncertain. METHODS: Patients with type 2 diabetes and documented CAD
      participating in the Bypass Angioplasty Revascularization Investigation 2
      Diabetes trial at 45 clinical sites in the United States and Canada were studied
      in a cross-sectional analysis of baseline data. Quality of life was assessed with
      the Duke Activity Status Index, the energy/fatigue and health distress scales
      from the Medical Outcome Study, and overall self-rated health status. RESULTS:
      Higher body mass index was significantly associated with worse scores on all 4
      quality of life scales, even after adjustment for the severity of diabetes and
      CAD and other comorbid conditions. Use of insulin, angina, and current smoking
      were also associated with significantly lower quality of life on all 4 scales,
      independent of other factors. CONCLUSIONS: Obesity is associated with
      significantly reduced quality of life in patients with diabetes and CAD,
      independent of comorbid conditions.

PMID- 20152230
TI  - Perioperative outcomes in reoperative cardiac surgery guided by cardiac
      multidetector computed tomographic angiography.
AB  - BACKGROUND: Preoperative evaluation with contrast-enhanced multidetector computed
      tomographic angiography (MDCTA) is considered an "appropriate" indication based
      on expert consensus. We aimed to evaluate how the presurgical evaluation with
      MDCTA impacts the outcomes after reoperative cardiac surgery (RCS). METHODS: We
      retrospectively studied 364 patients undergoing RCS between 2004 and 2008,
      including 137 referred for MDCTA. High-risk CT findings were defined as the
      presence of right ventricle or aorta <10 mm from the sternum or a bypass graft
      <10 mm from the sternum crossing the midline. The primary clinical end point was
      the composite of perioperative death, myocardial infarction (MI), stoke, and
      hemorrhage-related reoperation. Secondary end points included surgical procedural
      variables and the perioperative volume of bleeding and of red blood cell (RBC)
      transfusion. RESULTS: Baseline clinical characteristics were similar between the
      2 groups. Individuals referred for MDCTA showed a trend toward a lower incidence
      of the composite primary end point (17.5% vs 24.2%, P = .13), primarily related
      to a significantly lower incidence of perioperative MI (0% vs 5.7%, P = .002).
      Multidetector computed tomographic angiography was also associated with shorter
      perfusion (90 vs 110 minutes, P = .002), cross clamp time (63 vs 75 minutes, P =
      .003), and total time in intensive care unit (103 vs 148 hours, P = .04), and a
      lower volume of postoperative RBC transfusion (627 vs 824 mL, P = .09). These
      differences remained significant after adjustment for the Society of Thoracic
      Surgeons score and the performing surgeon. CONCLUSION: The use of MDCTA before
      RCS was associated with shorter perfusion and cross clamp time, shorter intensive
      care unit stays, and less frequent perioperative MI.

PMID- 20152231
TI  - Association of statin prescription with small abdominal aortic aneurysm
      progression.
AB  - BACKGROUND: Statins have been suggested to reduce expansion of abdominal aortic
      aneurysms (AAAs) independent of lipid-lowering effects. METHODS: We assessed the
      association of statin treatment and serum low-density lipoprotein (LDL)
      concentrations with small AAA expansion. Six hundred fifty-two patients
      undergoing surveillance of small AAAs were entered into the study from 5 vascular
      centers. In a subset, fasting lipids (n = 451) and other biomarkers (n = 216)
      were measured. The AAA diameter was followed by ultrasound surveillance for a
      median of 5 years. RESULTS: Three hundred forty-nine (54%) of the patients were
      prescribed statins. Adjusting for other risk factors, statin prescription was not
      associated with AAA growth (odds ratio [OR] 1.23, 95% CI 0.86-1.76). Above-median
      AAA growth was positively associated with initial diameter (OR 1.78 per 4.35-mm
      larger initial aortic diameter, 95% CI 1.49-2.14) and negatively associated with
      diabetes (OR 0.37, 95% CI 0.22-0.62). Above-median serum LDL concentration was
      not associated with AAA growth. Patients receiving statins had lower serum C
      reactive protein concentrations but similar matrix metalloproteinase-9 and
      interleukin-6 concentrations to those not prescribed these medications.
      CONCLUSIONS: We found no association between statin prescription or LDL
      concentration with AAA expansion. The results do not support the findings of
      smaller studies and suggest that statins may have no benefit in reducing AAA
      progression.

PMID- 20152232
TI  - The right ventricular annular velocity reduction caused by coronary artery bypass
      graft surgery occurs at the moment of pericardial incision.
AB  - BACKGROUND: Right ventricular (RV) long-axis function is known to be depressed
      after cardiac surgery, but the mechanism is not known. We hypothesized that
      intraoperative transesophageal echocardiography could pinpoint the time at which
      this happens to help narrow the range of plausible mechanisms. METHOD:
      Transthoracic echocardiography was conducted in 33 patients before and after
      elective coronary artery bypass graft. In an intensively monitored cohort of 9
      patients, we also monitored RV function intraoperatively using serial pulsed wave
      tissue Doppler (PW TD) transesophageal echocardiography. RESULTS: There was no
      significant difference in myocardial velocities from the onset of the operation
      up to the beginning of pericardial incision, change in RV PW TD S' velocities 3%
      +/- 2% (P = not significant). Within the first 3 minutes of opening the
      pericardium, RV PW TD S' velocities had reduced by 43% +/- 17% (P < .001). At 5
      minutes postpericardial incision, 2 minutes later, the velocities had more than
      halved, by 54% +/- 11% (P < .0001). Velocities thereafter remained depressed
      throughout the operation, with final intraoperative S' reduction being 61% +/-
      11% (P < .0001). One month after surgery, in the full 33-patient cohort,
      transthoracic echocardiogram data showed a 55% +/- 12% (P < .0001) reduction in
      RV S' velocities compared with preoperative values. CONCLUSIONS: Minute-by-minute
      monitoring during cardiac surgery reveals that, virtually, all the losses in RV
      systolic velocity occurs within the first 3 minutes after pericardial incision.
      Right ventricular long-axis reduction during coronary bypass surgery results not
      from cardiopulmonary bypass but rather from pericardial incision.

PMID- 20152233
TI  - Relationship between the logistic EuroSCORE and the Society of Thoracic Surgeons
      Predicted Risk of Mortality score in patients implanted with the CoreValve
      ReValving system--a Bern-Rotterdam Study.
AB  - BACKGROUND: Surgical risk scores, such as the logistic EuroSCORE (LES) and
      Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score, are
      commonly used to identify high-risk or "inoperable" patients for transcatheter
      aortic valve implantation (TAVI). In Europe, the LES plays an important role in
      selecting patients for implantation with the Medtronic CoreValve System. What is
      less clear, however, is the role of the STS score of these patients and the
      relationship between the LES and STS. OBJECTIVE: The purpose of this study is to
      examine the correlation between LES and STS scores and their performance
      characteristics in high-risk surgical patients implanted with the Medtronic
      CoreValve System. METHODS: All consecutive patients (n = 168) in whom a CoreValve
      bioprosthesis was implanted between November 2005 and June 2009 at 2 centers
      (Bern University Hospital, Bern, Switzerland, and Erasmus Medical Center,
      Rotterdam, The Netherlands) were included for analysis. Patient demographics were
      recorded in a prospective database. Logistic EuroSCORE and STS scores were
      calculated on a prospective and retrospective basis, respectively. RESULTS:
      Observed mortality was 11.1%. The mean LES was 3 times higher than the mean STS
      score (LES 20.2% +/- 13.9% vs STS 6.7% +/- 5.8%). Based on the various LES and
      STS cutoff values used in previous and ongoing TAVI trials, 53% of patients had
      an LES > or =15%, 16% had an STS > or =10%, and 40% had an LES > or =20% or STS >
      or =10%. Pearson correlation coefficient revealed a reasonable (moderate) linear
      relationship between the LES and STS scores, r = 0.58, P < .001. Although the STS
      score outperformed the LES, both models had suboptimal discriminatory power (c
      statistic, 0.49 for LES and 0.69 for STS) and calibration. CONCLUSIONS: Clinical
      judgment and the Heart Team concept should play a key role in selecting patients
      for TAVI, whereas currently available surgical risk score algorithms should be
      used to guide clinical decision making.

PMID- 20152234
TI  - Relation of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1
      ratio in peripheral circulating CD14+ monocytes to progression of coronary artery
      disease.
AB  - Atherosclerosis is an inflammatory disease in which systemic inflammation
      correlates with disease activity. Matrix metalloproteinases (MMPs) contribute to
      collagen breakdown in atherosclerotic plaques. In the present study, we
      investigated whether the ratio of MMP-9 and its endogenous inhibitor, tissue
      inhibitor of metalloproteinase (TIMP)-1, in circulating monocytes correlates with
      the clinical stages of coronary artery disease. We studied 18 patients with
      stable angina pectoris (SAP), 14 patients with unstable angina pectoris and non
      ST-segment elevation myocardial infarction (UAP/NSTEMI), 14 patients with ST
      elevation myocardial infarction (STEMI), and 16 healthy controls. The protein and
      mRNA levels of MMP-9 and TIMP-1 in CD14+ monocytes were analyzed using real-time
      polymerase chain reaction and enzyme-linked immunosorbent assay. The activity of
      serum MMP-9 was assessed using zymography. Compared to the controls (0.07 +/-
      0.01 relative units) and patients with SAP (0.25 +/- 0.1 relative units, p = NS),
      the monocytic MMP-9 mRNA levels were increased in those with UAP/NSTEMI (0.9 +/-
      0.3 relative units, p <0.05 vs SAP) or STEMI (1.6 +/- 0.4 relative units, p <0.05
      vs UAP/NSTEMI). In contrast, the protein and mRNA expression of monocytic TIMP-1
      levels was 4.5- to 4.7-fold lower in patients with STEMI than in the controls or
      those with SAP or UAP/NSTEMI (p <0.05). Changes in monocytic expression of MMP-9
      and TIMP-1 tracked with the serum levels of MMP-9 and TIMP-1. The activity of
      serum MMP-9 correlated with the individual MMP-9/TIMP-1 ratio in the peripheral
      circulating monocytes (r(2) = 0.82, p <0.02). In conclusion, the progression of
      coronary artery disease was mirrored by an increasing MMP-9/TIMP-1 ratio in the
      peripheral circulating CD14+ monocytes and serum, respectively. Circulating
      monocytes displayed the same pattern of imbalance in the expression of MMP-9 and
      TIMP-1 as previously reported for monocyte-derived macrophages within
      atherosclerotic plaques, supporting the notion of atherosclerosis as a systemic
      inflammatory disease.

PMID- 20152235
TI  - Hematocrit level as a marker of outcome in ST-segment elevation myocardial
      infarction.
AB  - Anemia is a well-known predictor of a poor outcome in patients with ST-segment
      elevation myocardial infarction (STEMI). In contrast, data relating
      erythrocytosis to clinical outcomes in patients with STEMI are limited. Because
      erythrocytosis predisposes to a prothrombotic state, we hypothesized it would be
      associated with an increased risk of thrombotic complications in patients with
      STEMI undergoing primary percutaneous coronary intervention. We studied 1,042
      consecutive patients with STEMI who underwent primary percutaneous coronary
      intervention and were a part of our primary percutaneous coronary intervention
      registry from 2001 to 2007. Patients with cardiogenic shock and late arrival were
      excluded. Patients were allocated into 3 groups according to their baseline
      hematocrit: anemia (<36% for women and <39% for men), normal, erythrocytosis
      (>46% for women and >47% for men). The clinical outcomes were assessed at 1, 6,
      and 12 months. The patients with anemia had the greatest clinical risk profile.
      Patients with erythrocytosis had a lower risk profile than the other 2 groups,
      except for greater rates of smoking. The mortality rates were greatest among the
      patients with anemia, followed by the patients with erythrocytosis, who in turn
      had greater short-term mortality than patients with normal hematocrit.
      Multivariate analysis, which included patients with erythrocytosis and those with
      normal hematocrit (excluding the patients with anemia), revealed that
      erythrocytosis was associated with an odds ratio of 4.3 (95% confidence interval
      1.4 to 13, p = 0.01) for 1-month mortality. In conclusion, although not as strong
      a predictor of mortality as anemia, erythrocytosis might be associated with
      increased short-term mortality compared to a normal hematocrit. The measurement
      of hematocrit can be used as a useful prognostic marker in patients with STEMI.

PMID- 20152236
TI  - Relation between thrombolysis in myocardial infarction risk score and one-year
      outcomes for patients presenting at the emergency department with potential acute
      coronary syndrome.
AB  - The Thrombolysis in Myocardial Infarction (TIMI) score, derived from unstable
      angina/non-ST-segment elevation acute myocardial infarction patient population,
      predicts 14-day cardiovascular events. It has been validated in emergency
      department (ED) patients with potential acute coronary syndrome with respect to
      30-day outcomes. Our objective was to determine whether the initial TIMI score
      could risk stratify ED patients with potential acute coronary syndrome with
      respect to the 1-year outcomes. This was a prospective cohort study of patients
      presenting to the ED with chest pain who underwent electrocardiography. Patients
      with ST-segment elevation myocardial infarction (acute myocardial infarction)
      were excluded. Follow-up was conducted by telephone and record review >1 year
      after the index visit. The main outcome was the 1-year mortality, nonfatal acute
      myocardial infarction, or revascularization stratified by the TIMI score. Of
      2,819 patients, 253 (9%) met the composite outcome. The overall incidence of the
      composite 1-year outcome of death (n = 119), acute myocardial infarction (n =
      96), and revascularization (n = 90) according to TIMI score was TIMI 0 (n =
      1,162), 4%; TIMI 1 (n = 901), 8%; TIMI 2 (n = 495), 13%; TIMI 3 (n = 193), 23%;
      TIMI 4 (n = 60), 28%; and TIMI 5 to 7 (n = 8), 88% (p <0.001). In conclusion, in
      addition to risk stratifying ED patients with chest pain at the initial ED
      evaluation, the TIMI score can also predict the 1-year cardiovascular events in
      this patient population.

PMID- 20152237
TI  - Current use of aspirin and antithrombotic agents in the United States among
      outpatients with atherothrombotic disease (from the REduction of Atherothrombosis
      for Continued Health [REACH] Registry).
AB  - Despite its proven efficacy, low cost, and wide availability, aspirin remains
      underused. We examined current aspirin use and determined factors that influence
      its use among outpatients in the United States (US). The REduction of
      Atherothrombosis for Continued Health (REACH) Registry is an international,
      prospective, longitudinal study of >68,000 outpatients with established
      atherothrombosis or >or=3 atherothrombotic risk factors. The rates of aspirin use
      were compared in various patient subgroups. Multivariate logistic regression
      models were constructed to determine the factors influencing the baseline use of
      aspirin and other antithrombotic agents in the US population. Approximately 70%
      of 25,686 US outpatients were treated with aspirin, with greater use in the
      Midwest and among men, whites, and those aged <65 years. Among aspirin users, 18%
      took other antiplatelet agents and 6% took oral anticoagulants. Low-dose aspirin
      (<or=100 mg/day) was used in approximately 2/3 of aspirin users. Of patients not
      taking aspirin, 1/2 were receiving oral anticoagulants or other antiplatelet
      agents. However, 15% of patients used no antithrombotic agent at all. Female
      gender, current smoking, or having diabetes mellitus were predictors of a lack of
      antithrombotic use; white race, atrial fibrillation or vascular disease, the use
      of other risk-reducing medications, or treatment by a cardiologist were
      associated with a greater likelihood of receiving antithrombotic therapy. In
      conclusion, approximately 1/4 of US patients with vascular disease are not
      treated with aspirin for secondary prevention, and 15% are not treated with any
      antithrombotic agent.

PMID- 20152238
TI  - Noninvasive assessment of gender differences in coronary plaque composition with
      multidetector computed tomographic angiography.
AB  - To date, sparse data are available with regard to gender differences in plaque
      morphology and composition. The aim of the present report was to assess the
      differences in coronary plaque burden and composition in a noninvasive manner
      between women and men using multidetector computed tomographic angiography. The
      study population consisted of 416 patients (61 +/- 13 years), with 148 women
      (36%). A stenosis of >or=70% in at least one coronary segment was found in 11% of
      women compared to 25% of men (p <0.0001). Overall, women presented with a
      significantly lower mean number of segments containing calcified plaques (1.43 +/
      2.04 vs 2.25 +/- 2.30, p = 0.004) and mixed plaques (1.67 +/- 1.23 vs 2.25 +/-
      2.30, p = 0.05). No such relation was seen with noncalcified plaques (0.72 +/-
      1.01 vs 0.86 +/- 1.06, p = 0.21). In addition, the assessment of the overall
      proportion of the composition of plaque burden revealed relatively more
      noncalcified (40% vs 28%), less calcified (38% vs 43%), and mixed (23% vs 28%)
      plaques in women than in men (p <0.0001). On multivariate analysis of the total
      plaque burden, the women had a 19% (95% confidence interval 11% to 28%, p
      <0.0001) greater relative distribution of plaque that was noncalcified compared
      to the men, and the overall plaque burden was less likely to be calcified (p =
      0.006) or mixed (p = 0.019). Similar results were seen in younger and older
      subjects. In conclusion, gender differences exist, not only in the
      atherosclerotic disease burden, but also in the underlying plaque composition.
      Women tended to have more exclusively noncalcified plaque and were less likely to
      have calcified or mixed plaques compared to men. Future studies are needed to
      elucidate whether these underlying differences in plaque composition might
      explain the reduced risk of cardiac events in women.

PMID- 20152239
TI  - Relation of oxidative biomarkers, vascular dysfunction, and progression of
      coronary artery calcium.
AB  - The relation between oxidative stress and coronary artery calcium (CAC)
      progression is currently not well described. The present study evaluated the
      relation among the biomarkers of oxidative stress, vascular dysfunction, and CAC.
      Sixty asymptomatic subjects participated in a randomized trial evaluating the
      effect of aged garlic extract plus supplement versus placebo and underwent
      measurement of CAC. The postcuff deflation temperature-rebound index of vascular
      function was assessed using a reactive hyperemia procedure. The content of
      oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles detected
      by antibody E06 (OxPL/apoB), lipoprotein(a), IgG and IgM autoantibodies to
      malondialdehyde-low-density lipoprotein and apoB-immune complexes were measured
      at baseline and after 12 months of treatment. CAC progression was defined as an
      annual increase in CAC >15%. Vascular dysfunction was defined according to the
      tertiles of temperature-rebound at 1 year of follow-up. From baseline to 12
      months, a strong inverse correlation was noted between an increase in CAC scores
      and increases in temperature-rebound (r(2) = -0.90), OxPL/apoB (r(2) = -0.85),
      and lipoprotein(a) (r(2) = -0.81) levels (p <0.0001 for all). The improvement in
      temperature-rebound correlated positively with the increases in OxPL/apoB (r(2) =
      0.81, p = 0.0008) and lipoprotein(a) (r(2) = 0.79, p = 0.0001) but inversely with
      autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune
      complexes. The greatest CAC progression was noted with the lowest tertiles of
      increases in temperature-rebound, OxPL/apoB and lipoprotein(a) and the highest
      tertiles of increases in IgG and IgM malondialdehyde-low-density lipoprotein. In
      conclusion, the present results have documented a strong relation among markers
      of oxidative stress, vascular dysfunction, and progression of coronary
      atherosclerosis. Increases in OxPL/apoB and lipoprotein(a) correlated strongly
      with increases in vascular function and predicted a lack of progression of CAC.

PMID- 20152240
TI  - Predictive value of ST resolution analysis performed immediately versus at ninety
      minutes after primary percutaneous coronary intervention.
AB  - ST segment resolution (STR) predicts epicardial and microvascular reperfusion
      after primary percutaneous coronary intervention (PPCI) or thrombolysis for ST
      elevation myocardial infarction. Immediate restoration of epicardial coronary
      flow, with improved microvascular perfusion, is much more likely with PPCI.
      However, the predictive value of immediate STR compared to 90 minutes after PPCI
      remains unknown. In 622 consecutive patients with ST-elevation myocardial
      infarction (mean age 59 +/- 13 years), 217 had complete STR immediately after
      PPCI (group A), 188 had complete STR only at 90 minutes (group B), and 217 had
      incomplete STR at either point (group C). The primary end point was mortality and
      adverse cardiovascular events ([MACE] death, nonfatal repeat myocardial
      infarction, and heart failure). Group A had a greater left ventricular ejection
      fraction (53%, 47%, and 46%, p <0.001) and lower all-cause mortality (1.8%, 3.2%,
      and 6%, p = 0.07), lower heart failure (1.8%, 4.3%, and 7.8%, p <0.001), and MACE
      (5.1%, 9.6%, and 16.1%, p = 0.001) at 30 days compared to groups B and C,
      respectively. The rate of MACE at 1 year was 7.6%, 17.1%, and 20.2% in groups A,
      B, and C, respectively (p <0.001). Immediate STR independently predicted MACE
      (adjusted hazard ratio 0.36, 95% confidence interval 0.21 to 0.61, p = 0.001,
      group A vs C), and STR at 90 minutes did not. In conclusion, STR analysis
      performed immediately after PPCI provided superior differentiation for adverse
      cardiovascular events compared to STR at 90 minutes. Immediate STR should be the
      contemporary goal of reperfusion with PPCI.

PMID- 20152241
TI  - The impact of body mass index on the one year outcomes of patients treated by
      percutaneous coronary intervention with Biolimus- and Sirolimus-eluting stents
      (from the LEADERS Trial).
AB  - The aim of this analysis was to assess the effect of body mass index (BMI) on 1
      year outcomes in patients enrolled in a contemporary percutaneous coronary
      intervention trial comparing a sirolimus-eluting stent with a durable polymer to
      a biolimus-eluting stent with a biodegradable polymer. A total of 1,707 patients
      who underwent percutaneous coronary intervention were randomized to treatment
      with either biolimus-eluting stents (n = 857) or sirolimus-eluting stents (n =
      850). Patients were assigned to 1 of 3 groups according to BMI: normal (<25
      kg/m(2)), overweight (25 to 30 kg/m(2)), or obese (>30 kg/m(2)). At 1 year, the
      incidence of the composite of cardiac death, myocardial infarction, and
      clinically justified target vessel revascularization was assessed. In addition,
      rates of clinically justified target lesion revascularization and stent
      thrombosis were assessed. Cox proportional-hazards analysis, adjusted for
      clinical differences, was used to develop models for 1-year mortality. Forty-five
      percent of the patients (n = 770) were overweight, 26% (n = 434) were obese, and
      29% (n = 497) had normal BMIs. At 1-year follow-up, the cumulative rate of
      cardiac death, myocardial infarction, and clinically justified target vessel
      revascularization was significantly higher in the obese group (8.7% in normal
      weight, 11.3% in overweight, and 14.5% in obese patients, p = 0.01). BMI (hazard
      ratio 1.47, 95% confidence interval 1.02 to 2.14, p = 0.04) was an independent
      predictor of stent thrombosis. Stent type had no impact on the composite of
      cardiac death, myocardial infarction, and clinically justified target vessel
      revascularization at 1 year in the 3 BMI groups (hazard ratio 1.08, 95%
      confidence interval 0.63 to 1.83, p = 0.73). In conclusion, BMI was an
      independent predictor of major adverse cardiac events at 1-year clinical follow
      up. The higher incidence of stent thrombosis in the obese group may suggest the
      need for a weight-adjusted dose of clopidogrel.

PMID- 20152242
TI  - Assessment with multi-slice computed tomography and gray-scale and virtual
      histology intravascular ultrasound of gender-specific differences in extent and
      composition of coronary atherosclerotic plaques in relation to age.
AB  - Data evaluating gender- and age-specific differences in plaque observations on
      multislice computed tomography (MSCT) are scarce. Accordingly, the aim of this
      study was to evaluate coronary plaque patterns in men and women in relation to
      age using MSCT. The findings were compared to observations on grayscale
      intravascular ultrasound (IVUS) and virtual histology (VH) IVUS. In total, 93
      patients (59 men, 34 women) underwent 64-slice MSCT followed by conventional
      coronary angiography with IVUS. Plaque extent and composition were assessed on
      MSCT, grayscale IVUS, and VH IVUS. Coronary plaque patterns were compared between
      men and women in 2 age groups (<65 and >or=65 years old). In patients aged <65
      years, more plaques were observed on MSCT in men (6 +/- 4 vs 2 +/- 2 in women, p
      <0.001). Also, a larger plaque burden was observed on grayscale IVUS in men (45.7
      +/- 11.4% vs 36.3 +/- 11.6% in women, p <0.001). Similarly, more mixed plaques
      were observed in men (3 +/- 3 vs 1 +/- 1 in women, p = 0.003), whereas a larger
      arc of calcium was detected on grayscale IVUS in men (91.7 +/- 93.5 degrees vs
      25.7 +/- 51.0 degrees in women, p <0.001). On VH IVUS, the prevalence of thin-cap
      fibroatheroma was higher in men (31% vs 0%) compared to women. In patients aged
      >or=65 years old, no important differences in plaque patterns were observed
      between men and women. In conclusion, more extensive atherosclerosis and more
      calcified lesions were observed in men than in women. These differences were
      predominantly present in patients aged <65 years and were lost in those aged
      >or=65 years.

PMID- 20152244
TI  - Prognostic implications of the high-sensitive C-reactive protein in the catheter
      ablation of atrial fibrillation.
AB  - Previous studies have reported that increased high-sensitive C-reactive protein
      (hs-CRP) levels are associated with an inflammatory state. This study
      investigated the association among hs-CRP, substrate properties, and long-term
      clinical outcomes after catheter ablation of atrial fibrillation (AF). A total of
      137 patients with AF (54 +/- 13 years) who underwent mapping and catheter
      ablation were included. The hs-CRP was measured before the first ablation
      procedure. The substrate properties (initiating triggers, biatrial mean voltage,
      and high-frequency sites) of the 2 atria and long-term outcome were investigated
      in patients in the low hs-CRP group (<75%, 2.92 mg/L) and high hs-CRP group
      (>75%, 2.92 mg/L). Patients with a higher hs-CRP were associated with an
      increased number of identified nonpulmonary vein ectopies (34.4% vs 17%, p =
      0.034), lower mean left atrial (LA) voltage (1.72 +/- 0.73 vs 1.92 +/- 0.72 Hz, p
      = 0.045), and higher-frequency sites in the left atrium (71% vs 37%, p = 0.027).
      After a median follow-up period of 15 months, the single-procedure success rate
      (72% vs 53%, p = 0.008) and final success rate after multiple procedures (94% vs
      81%, p = 0.02) were higher in the low hs-CRP group. In a multivariable regression
      model adjusted for other potential covariates, hs-CRP level (p = 0.021) and LA
      diameter (p = 0.032) were independent predictors of recurrence. In conclusion,
      baseline CRP levels before the first AF ablation procedure had an independent
      prognostic value in predicting long-term recurrence. Patients with a high hs-CRP
      level were associated with an abnormal LA substrate and high incidence of
      nonpulmonary vein AF sources.

PMID- 20152243
TI  - Long-term safety and efficacy of triple combination ezetimibe/simvastatin plus
      extended-release niacin in patients with hyperlipidemia.
AB  - The safety and efficacy of combination ezetimibe/simvastatin (E/S) plus extended
      release niacin was assessed in 942 patients with type IIa/IIb hyperlipidemia for
      64 weeks in a randomized, double-blind study. Patients received E/S (10/20 mg)
      plus niacin (to 2 g) or E/S (10/20 mg) for 64 weeks, or niacin (to 2 g) for 24
      weeks and then E/S (10/20 mg) plus niacin (2 g) or E/S (10/20 mg) for an
      additional 40 weeks. The primary end point, the safety of E/S plus niacin,
      included prespecified adverse events (ie, liver, muscle, discontinuations due to
      flushing, gallbladder-related, cholecystectomy, fasting glucose changes, new
      onset diabetes). The secondary end points included the percentage of change from
      baseline in high-density lipoprotein (HDL) cholesterol, triglycerides, non-HDL
      cholesterol, and low-density lipoprotein cholesterol, other lipids, lipoprotein
      ratios and high-sensitivity C-reactive protein. The anticipated niacin-associated
      flushing led to a greater rate of study discontinuations with the E/S plus niacin
      regimen than with E/S alone (0.7%, p <0.001). The rate of liver and muscle
      adverse events was low (<1%) in both groups. Four patients had gallbladder
      related adverse events; 1 patient in the E/S and 1 in the E/S plus niacin group
      underwent cholecystectomy. The occurrence of new-onset diabetes was 3.1% for the
      E/S and 4.9% for the E/S plus niacin group. The fasting glucose levels increased
      to greater than baseline during the first 12 weeks (E/S, 3.2 mg/dl; E/S plus
      niacin, 7.7 mg/dl) and gradually decreased to pretreatment levels by 64 weeks in
      both groups. E/S plus niacin significantly improved HDL cholesterol,
      triglycerides, non-HDL cholesterol, low-density lipoprotein cholesterol,
      apolipoprotein B and A-I, and lipoprotein ratios compared with E/S (p <or=0.004).
      The changes in high-sensitivity C-reactive protein were comparable for both
      groups. In conclusion, the combination of E/S plus niacin was generally well
      tolerated, aside from niacin-associated flushing, and was significantly superior
      to E/S alone in improving several lipoprotein parameters during a 64-week trial
      in patients with hyperlipidemia. E/S plus niacin provided a broad, lipid-altering
      therapeutic option for these patients, even in the presence of diabetes with
      glucose monitoring.

PMID- 20152245
TI  - Thromboembolism in atrial fibrillation.
AB  - Thromboembolism is a severe complication in atrial fibrillation. This overview
      presents thromboembolic disease as a single entity, ranging from stroke through
      mesenteric ischemia to acute limb ischemia. The PubMed, Embase, and Cochrane
      databases were systematically searched for the terms "atrial fibrillation" and
      "thromboembolism" in reports published from January 1986 to September 2009. The
      information of 10 evidence-based practice guideline documents and 61 further
      sources was systematically extracted. In atrial fibrillation, the average annual
      stroke risk is increased by 2.3% (lethality 30%). The annual incidence of acute
      mesenteric ischemia is 0.14% (lethality 70%), and that of acute limb ischemia is
      0.4% (lethality 16%). In total, approximately 80% of embolism-related deaths are
      from stroke and 20% from other systemic thromboembolism. The ischemic symptoms
      generally have an acute onset but may mimic other diseases, particularly in
      mesenteric ischemia. Early diagnosis and treatment can limit or even prevent
      tissue infarction. Guideline-recommended therapy with aspirin or warfarin reduces
      the thromboembolic risk. Suitable patients may optimize their warfarin therapy by
      self-monitoring of the international normalized ratio (INR). New oral and
      parenteral anticoagulants with more stable pharmacokinetics are being developed.
      In conclusion, atrial fibrillation predisposes to thromboembolism. If ischemic
      stroke or systemic thromboembolism occurs, early diagnosis and treatment can
      improve outcomes. The thromboembolic risks are reduced by guideline-adherent
      antithrombotic therapy with warfarin or aspirin. Future directions may include
      self-monitoring of the international normalized ratio and novel anticoagulants.

PMID- 20152246
TI  - Effect of right ventricular function and venous congestion on cardiorenal
      interactions during the treatment of decompensated heart failure.
AB  - Recent reports have demonstrated the adverse effects of venous congestion on
      renal function (RF) and challenged the assumption that worsening RF is driven by
      decreased cardiac output (CO). We hypothesized that diuresis in patients with
      right ventricular (RV) dysfunction, despite decreased CO, would lead to a
      decrease in venous congestion and resultant improvement in RF. We reviewed
      consecutive admissions with a discharge diagnosis of heart failure. RV function
      was assessed by multiple echocardiographic methods and those with >or=2
      measurements of RV dysfunction were considered to have significant RV
      dysfunction. Worsening RF was defined as an increase in creatinine of >or=0.3
      mg/dl and improved RF as improvement in glomerular filtration rate >or=25%. A
      total of 141 admissions met eligibility criteria; 34% developed worsening RF.
      Venous congestion was more common in those with RV dysfunction (odds ratio [OR]
      3.3, p = 0.009). All measurements of RV dysfunction excluding RV dilation
      correlated with CO (p <0.05). Significant RV dysfunction predicted a lower
      incidence of worsening RF (OR 0.21, p <0.001) and a higher incidence of improved
      RF (OR 6.4, p <0.001). CO emerged as a significant predictor of change in
      glomerular filtration rate during hospitalization in those without significant RV
      dysfunction (r = 0.38, p <0.001). In conclusion, RV dysfunction is a strong
      predictor of improved renal outcomes in patients with acute decompensated heart
      failure, an effect likely mediated by relief of venous congestion.

PMID- 20152248
TI  - Usefulness of cardiac resynchronization therapy in patients with Adriamycin
      induced cardiomyopathy.
AB  - Adriamycin is a chemotherapeutic agent that can cause severe cardiotoxicity,
      which potentially carries a poorer long-term prognosis than other forms of
      cardiomyopathy. Cardiac resynchronization therapy (CRT) has been shown to improve
      quality of life, exercise capacity, left ventricular ejection fraction, and
      survival in selected patients with heart failure. It is unclear if patients with
      Adriamycin-induced cardiomyopathy (AIC) respond to CRT. We reviewed clinical and
      echocardiographic data on 18 consecutive patients with AIC who underwent
      implantation of a CRT device at the Cleveland Clinic from February 2000 to April
      2007. Changes in clinical and echocardiographic parameters were compared to 189
      consecutive patients with other forms of nonischemic cardiomyopathy (NIC) using
      similar end points. Patients with AIC demonstrated significant improvements in
      ejection fraction, left ventricular end-diastolic and end-systolic diameters,
      mitral regurgitation, and New York Heart Association functional class with CRT.
      These changes were similar to patients in the NIC cohort. In conclusion, patients
      with AIC may derive a significant echocardiographic and symptomatic benefit from
      CRT, which is similar to that seen in other forms of NIC.

PMID- 20152247
TI  - Effects of rosuvastatin on coronary flow reserve and metabolic mismatch in
      patients with heart failure (from the CORONA Study).
AB  - In patients with heart failure (HF), statin treatment might improve myocardial
      perfusion, but could also have detrimental effects on myocardial metabolism. A
      predefined substudy of the Controlled Rosuvastatin Multinational Trial in Heart
      Failure (CORONA) trial sought to determine the effects of statin treatment on
      myocardial blood flow reserve and cardiac metabolism. Sixteen patients with HF
      (New York Heart Association class II or III) were randomized to rosuvastatin 10
      mg/day (n = 8) or placebo treatment (n = 8). At baseline and after 6 months of
      treatment, nitrogen-13 ammonia at rest and after dipyridamole stress and 18
      fluorodeoxyglucose positron emission tomography were performed. Rosuvastatin
      treatment significantly lowered total (-36%, p <0.01) and low-density lipoprotein
      (-47%, p <0.001) cholesterol and C-reactive protein levels (-36%, p <0.05).
      Myocardial perfusion reserve (ratio) changed from 1.64 +/- 0.90 to 1.30 +/- 0.37
      in placebo-treated and from 1.51 +/- 0.18 to 1.55 +/- 0.34 in rosuvastatin
      treated patients (p = NS). Metabolic mismatch changed from 4.25 +/- 2.37% to 4.38
      +/- 3.81% in placebo-treated and from 5.13 +/- 2.75% to 3.50 +/- 2.73% in
      rosuvastatin-treated patients (p = NS). In conclusion, changes regarding
      myocardial perfusion and metabolic mismatch after 6 months of rosuvastatin
      treatment in patients with HF did not suggest any beneficial or adverse effects
      in this pilot study, although due to the small numbers of patients small effects
      might have been missed.

PMID- 20152249
TI  - Comparison of prognostic value of tissue Doppler imaging in carcinoid heart
      disease versus the value in patients with the carcinoid syndrome but without
      carcinoid heart disease.
AB  - The aim of this study was to evaluate the prognostic value of tissue Doppler
      imaging (TDI) in carcinoid heart disease (CHD). We prospectively enrolled 56
      consecutive patients with proved digestive endocrine tumor and carcinoid
      syndrome. All patients underwent serial conventional, contrast, and TDI
      echocardiographic studies. The end point was all-cause mortality. Mean follow-up
      was 34 +/- 21 months. At the end of follow-up, 30 patients (54%) presented right
      CHD and 13 patients (23%) left CHD. A progression of CHD was documented in 23
      patients (41%). Twenty-two patients (39%) died during follow-up. According to
      mortality receiver operating characteristic curves, ratio of early transmitral
      flow velocity to early diastolic mitral annulus velocity (E/e' ratio) associated
      with an optimal sensitivity of 80% and specificity of 90% was 8. Mortality rate
      was significantly higher when the E/e' ratio was >or=8 (94% vs 10% when E/e'
      ratio was <8, p <0.0001). Using univariate analysis, the following factors were
      associated with death: left-sided CHD (p = 0.07) and E/e' ratio >or=8 (p
      <0.0001). The only independent marker of death detected by multivariate analysis
      was an E/e' ratio >or=8 (odds ratio 6.2, 95% confidence interval 1.95 to 19.7, p
      = 0.002). In conclusion, TDI used during routine transthoracic echocardiography
      can be helpful to identify high-risk patients with CHD.

PMID- 20152250
TI  - Morphologic features of exertional versus nonexertional sudden death in patients
      with hypertrophic cardiomyopathy.
AB  - Pathologic features that characterize hypertrophic cardiomyopathy (HC) in
      exertional versus nonexertional sudden deaths have not been extensively studied.
      We performed gross measurements and histologic analysis on 103 autopsy cases of
      HC and correlated these with clinical findings. Pathologic features of the 71
      sudden deaths were compared between exertional and nonexertional deaths. Age at
      death was significantly younger in exertional (27 +/- 13 years) versus
      nonexertional sudden deaths (40 +/- 16 years, p = 0.0003). Exertional deaths were
      more likely in women (35 of 37) versus sudden deaths at rest (21 of 34, p =
      0.0002). There was no significant difference in the incidence of syncope in the
      exertional sudden deaths (14%) compared to the nonexertional sudden deaths (9%, p
      = 0.5) or in the rate of a previous diagnosis of HC (21% vs 21%, respectively).
      Mean heart weight was significantly decreased in exertional sudden deaths versus
      nonexertional sudden deaths. There was no difference in the frequency of left
      ventricular outflow tract plaque (54% exertional vs 46% nonexertional, p = 0.06).
      By multivariate analysis, including all categories of HC, only decreased heart
      weight (p = 0.02) and male gender (p = 0.002) were significantly associated with
      exertional sudden death. In conclusion, there are no pathologic features that
      would identify patients with HC at risk for exertional death. Because relatively
      decreased heart weight is strongly associated with exertional death, and because
      a large proportion of exertional deaths with HC are not associated with
      significant asymmetry, cardiologists should be careful in excluding the diagnosis
      of HC in athletes with even mild degrees of cardiomegaly, especially young men.

PMID- 20152251
TI  - Sexuality and reproductive health in women with congenital heart disease.
AB  - The different biopsychosocial periods in a woman's life are all interactively
      associated with the cardiovascular system. The present study was designed to
      address questions related to sexuality and reproductive health in a large cohort
      of women with congenital heart disease. Overall, 536 women (median age 29 years,
      range 18 to 75) completed a questionnaire during their visit at 2 tertiary care
      centers for congenital heart disease. Patients were categorized according to
      their functional class and according to the degree of severity of the underlying
      heart defect. The median age at menarche was significantly delayed in patients
      with functional class III-IV and in women with complex or cyanotic anomalies.
      More than 1/4 of the women (29%) had at least once sought medical advice for
      menstrual discomforts, and the proportion was significantly increased for those
      in the worst functional class (49%, p <0.001) and for patients with a cyanotic
      heart defect (43%, p = 0.03). Overall, 9% reported increased or altered symptoms
      related to their heart defect during sexual activity. This proportion increased
      significantly with worsening functional class (6%, 11%, and 26% in functional
      class I, II, and III-IV, respectively; p = 0.001), increased severity (5%, 8%,
      and 17% for simple, moderate, and severe heart defects, respectively; p = 0.005),
      and in women with cyanosis (8% and 28% in acyanotic and cyanotic patients,
      respectively; p <0.001). In conclusion, to ensure high-quality care for this
      demanding and growing patient population, physicians must be aware that issues
      related to the entire reproductive cycle should be considered when counseling
      these patients.

PMID- 20152252
TI  - Anatomic, imaging, and clinical characteristics of double-inlet, double-outlet
      right ventricle.
AB  - The purposes of this study were to characterize the morphologic, imaging, and
      clinical characteristics of double-inlet, double-outlet right ventricle (DI
      DORV), a rare congenital heart disease, and to compare these findings to those in
      patients with double-inlet left ventricle (DILV). The clinical records, imaging
      studies, and heart specimens of 22 consecutive patients with DI-DORV were
      reviewed. A comparison group of 44 patients with DILV was matched by age at
      latest follow-up. Among the 22 patients with DI-DORV, 14 had clinical data, 5 had
      clinical and autopsy data, and 3 had only autopsy data. Abdominal and atrial
      situs were normal in all, and heart position was levocardia in 91%. The
      morphology of the atrioventricular valves was variable, with 15 patients showing
      neither a typical tricuspid nor mitral valve. In the remaining 7 patients, 1 or
      both atrioventricular valves resembled a tricuspid or a mitral valve. Myocardial
      architecture was characterized by atypical muscle bundles of varying degrees of
      hypertrophy and orientation. Most patients had bilateral conus, and 82% had
      either aortic or pulmonary outflow tract obstructions. The rate of overall
      mortality or heart transplantation was 36%. Significant differences between DI
      DORV and DILV included the type of ventricular loop, the type of conus, and a
      higher mortality rate in patients with DI-DORV. In conclusion, DI-DORV is a
      distinct type of functional single ventricle congenital heart disease with
      variable atrioventricular valve morphology and myocardial architecture. Accurate
      diagnosis using noninvasive imaging techniques is of paramount importance for
      optimal management.

PMID- 20152254
TI  - The Editor's Roundtable: Health reform and its implications for cardiovascular
      medicine.

PMID- 20152253
TI  - Structural and functional changes in left and right ventricles after major weight
      loss following bariatric surgery for morbid obesity.
AB  - Obesity and bariatric surgery have been associated with changes in ventricular
      function and structure. The aim of the present study was to assess the long-term
      changes in left ventricular (LV) and right ventricular (RV) function and
      structure in patients with morbid obesity-body mass index >or=40 kg/m(2) or
      >or=35 kg/m(2) with co-morbidities-who had lost weight after bariatric surgery
      compared to nonsurgical controls. We reviewed 57 patients with morbid obesity who
      had undergone gastric bypass surgery and who had undergone echocardiography
      before and after surgery. A reference group (n = 57) was frequency matched for
      body mass index (+/-2 kg/m(2)), gender, age (+/-2 years), and follow-up duration
      (+/-6 months). After a mean follow-up of 3.6 years, the LV mass and LV mass
      indexed by height had decreased in the patients who had undergone bariatric
      surgery and had lost weight. In contrast, these measurements had increased in the
      patients who had not undergone bariatric surgery. The difference between these 2
      groups remained significant after adjusting for potential confounders. At follow
      up, neither the patients nor controls showed a significant change in ejection
      fraction, LV myocardial performance index, or RV myocardial performance index. In
      the study population as a whole, multivariate analysis showed a positive
      correlation between the change in body weight and ventricular septum thickness (R
      = 0.33), posterior wall thickness (R = 0.31), LV mass (R = 0.38), RV end
      diastolic area (R = 0.22), and estimated RV systolic pressure (R = 0.39), all
      with p values <0.05. In conclusion, body weight changes in patients with morbid
      obesity were associated with changes in LV structure independent of improvement
      in obesity-related co-morbidities, including obstructive sleep apnea. Weight loss
      improved the RV end-diastolic area and might prevent progression to RV
      dysfunction.

PMID- 20152255
TI  - Renal sympathetic denervation and systemic hypertension.
AB  - Hypertension represents a major health problem, with an appalling annual toll.
      Despite the plethora of antihypertensive drugs, hypertension remains resistant in
      a considerable number of patients, thus creating the need for alternative
      strategies, including interventional approaches. Recently, renal sympathetic
      denervation (RSD) using a very elegant, state-of-the-art technique (percutaneous,
      catheter-based radiofrequency ablation) was shown to be beneficial in patients
      with resistant hypertension. The pathophysiology of kidney function justifies the
      use of RSD in the treatment of hypertension. Data from older studies have shown
      that sympathectomy has efficiently lowered blood pressure and prolonged the life
      expectancy of patients with hypertension, but at considerable cost. RSD is devoid
      of the adverse effects of sympathectomy because of its localized nature, is
      minimally invasive, and provides short procedural and recovery times. In
      conclusion, this review outlines the pathophysiologic background of RSD,
      describes the past and the present of this interventional approach, and considers
      several future potential applications.

PMID- 20152256
TI  - Aspirin--a drug whose time has gone?

PMID- 20152257
TI  - Triple therapy: triple safety or triple danger?

PMID- 20152258
TI  - Arsenic speciation in natural waters by cathodic stripping voltammetry.
AB  - Contamination of groundwater with arsenic (As) is a major health risk through
      contamination of drinking and irrigation water supplies. In geochemically
      reducing conditions As is mostly present as As(III), its most toxic species.
      Various methods exist to determine As in water but these are not suitable for
      monitoring arsenic speciation at its original pH and without preparation. We
      present a method that uses cathodic stripping voltammetry (CSV) to determine
      reactive As(III) at a vibrating, gold, microwire electrode. The As(III) is
      detected after adsorptive deposition of As(OH)(3)(0), followed by a potential
      scan to measure the reduction current from As(III) to As(0). The method is
      suitable for waters of pH 7-12, has an analytical range of 1 nM to 100 microM As
      (0.07-7500 ppb) and a limit of detection of 0.5 nM with a 60 s deposition time.
      The As speciation protocol involves measuring reactive As(III) by CSV at the
      original pH and acidification to pH 1 to determine inorganic As(III)+As(V) by
      anodic stripping voltammetry (ASV) using the same electrode. Total dissolved As
      is determined by ASV after UV-digestion at pH 1. The method was successfully
      tested on various raw groundwater samples from boreholes in the UK and West
      Bengal.

PMID- 20152259
TI  - Micellar extraction and high performance liquid chromatography-ultra violet
      determination of some explosives in water samples.
AB  - An analytical method based on the cloud point extraction combined with high
      performance liquid chromatography is used for the extraction, separation and
      determination of four explosives; octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazine
      (HMX), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT)
      and pentaerythritol tetranitrate (PETN). These compounds are extracted by using
      of Triton X-114 and cetyl-trimethyl ammonium bromide (CTAB). After extraction,
      the samples were analyzed using a HPLC-UV system. The parameters affecting
      extraction efficiency (such as Triton X-114 and CTAB concentrations, amount of
      Na(2)SO(4), temperature, incubation and centrifuge times) were evaluated and
      optimized. Under the optimum conditions, the preconcentration factor was 40 and
      the improvement factors of 34, 29, 61 and 42 with detection limits of 0.09, 0.14,
      0.08 and 0.40 (microg L(-1)) were obtained for HMX, RDX, TNT and PETN,
      respectively. The proposed method was successfully applied to the determination
      of these compounds in water samples and showed recovery percentages of 97-102%
      with RSD values of 2.13-4.92%.

PMID- 20152260
TI  - Development of a highly sensitive and selective hyphenated technique (molecularly
      imprinted micro-solid phase extraction fiber-molecularly imprinted polymer fiber
      sensor) for ultratrace analysis of folic acid.
AB  - A simple polymerization strategy is reported in this work which allows
      molecularly imprinted polymeric fiber (monolith) fabrication for direct use in
      sensing devices. This is advantageous for achieving higher degree of enrichment
      of target analyte (folic acid) from the complex matrices of real samples, without
      any surface fouling, cross-reactivity, and non-specific (false-positive)
      contributions. In order to measure serum folic acid at ultratrace level to detect
      spina bifida, a neural tube defect in mother, and other acute cases of proteomic
      diseases, the hyphenation between molecularly imprinted micro-solid phase
      extraction fiber and a complementary molecularly imprinted polymer-carbon
      composite fiber sensor has been found quite efficient. The primitive diagnosis of
      many chronic diseases is feasible by estimating folic acid as biomarker, with the
      detection limit as low as 0.0036 ng mL(-1) (relative standard deviation=0.13%,
      signal/noise=3) in human blood serum.

PMID- 20152261
TI  - New method for determination of trihalomethanes in exhaled breath: applications
      to swimming pool and bath environments.
AB  - A method for the estimation of the human intake of trihalomethanes (THMs), namely
      chloroform, bromodichloromethane, dibromochloromethane and bromoform, during
      showering and bathing is reported. The method is based on the determination of
      these compounds in exhaled breath that is collected by solid adsorption on Tenax
      using a device specifically designed for this purpose. Instrumental measurements
      were performed by automatic thermal desorption coupled to gas chromatography with
      electron capture detection. THMs in exhaled breath samples were determined during
      showering and swimming pool attendance. The levels of these compounds in indoor
      air and water were also determined as reference for interpretation of the exhaled
      breath results. The THM concentrations in exhaled breath of the volunteers
      measured before the exposure experiments showed a close correspondence with the
      THMs levels in indoor air where the sampler was located. Limits of detection in
      exhaled breath were dependent on THM analytes and experimental sites. They ranged
      between 170 and 710 ng m(-3) in the swimming pool studies and between 97 and 460
      ng m(-3) in the showering studies. Application of this method to THMs
      determination during showering and swimming pool activities revealed
      statistically significant increases in THMs concentrations when comparing exhaled
      breath before and after exposure.

PMID- 20152262
TI  - Determination of fluoroquinolone antibiotics in environmental water samples based
      on magnetic molecularly imprinted polymer extraction followed by liquid
      chromatography-tandem mass spectrometry.
AB  - A simple method based on magnetic separation for selective extraction of
      fluoroquinolones (FQs) from environmental water samples has been developed using
      magnetic molecularly imprinted polymer (MMIP) as sorbent. The MMIP has been
      prepared using ciprofloxacin as template molecule, methacrylic acid as functional
      monomer, ethylene glycol dimethacrylate as cross-linking agent and Fe(3)O(4)
      magnetite as magnetic component. The polymer has been characterized by scanning
      electron microscopy, Fourier-transform infrared spectrometry and vibrating sample
      magnetometry. Various parameters affecting the extraction efficiency were
      evaluated in order to achieve optimal concentration and reduce non-specific
      interactions. The analytes desorbed from the polymers were determined by liquid
      chromatography-tandem mass spectrometry. The matrix effect was evaluated by using
      different washing solvents for removing interfering compounds from the MMIPs
      after sample loading. Under the optimal conditions, the linearity of the method
      obtained is in the range of 20-2000 ng L(-1). The detection limits of FQs are in
      the range of 3.2-6.2 ng L(-1). The relative standard deviations of intra- and
      inter-day tests ranging from 2.5 to 7.2% and from 3.6 to 9.1% are obtained. In
      all three spiked levels (20, 100 and 200 ng L(-1)), the recoveries of FQs are in
      the range of 76.3-94.2%. The proposed method was successfully applied to
      determine FQs including ciprofloxacin, enrofloxacin, lomefloxacin, levofloxacin,
      fleroxacin and sparfloxacin in different water samples, such as lake water, river
      water, primary and final sewage effluent. Ciprofloxacin and fleroxacin were found
      in primary and final sewage effluent samples with the contents in the range of 26
      87 ng L(-1).

PMID- 20152263
TI  - Determination of the steroid hormone levels in water samples by dispersive liquid
      liquid microextraction with solidification of a floating organic drop followed by
      high-performance liquid chromatography.
AB  - In this study, the steroid hormone levels in river and tap water samples were
      determined by using a novel dispersive liquid-liquid microextraction method based
      on the solidification of a floating organic drop (DLLME-SFO). Several parameters
      were optimized, including the type and volume of the extraction and dispersive
      solvents, extraction time, and salt effect. DLLME-SFO is a fast, cheap, and easy
      to-use method for detecting trace levels of samples. Most importantly, this
      method uses less-toxic solvent. The correlation coefficient of the calibration
      curve was higher than 0.9991. The linear range was from 5 to 1000 microg L(-1).
      The spiked environmental water samples were analyzed using DLLME-SFO. The
      relative recoveries ranged from 87% to 116% for river water (which was spiked
      with 4 microg L(-1) for E1, 3 microg L(-1) for E2, 4 microg L(-1) for EE2 and 9
      microg L(-1) for E3) and 89% to 102% for tap water (which was spiked with 6
      microg L(-1) for E1, 5 microg L(-1) for E2, 6 microg L(-1) for EE2 and 10 microg
      L(-1) for E3). The detection limits of the method ranged from 0.8 to 2.7 microg
      L(-1) for spiked river water and 1.4 to 3.1 microg L(-1) for spiked tap water.
      The methods precision ranged from 8% to 14% for spiked river water and 7% to 14%
      for spiked tap water.

PMID- 20152264
TI  - Direct colorimetric detection of copper(II) ions in sampling using diffusive
      gradients in thin-films.
AB  - A novel binding phase was developed for use in diffusive gradients in thin-film
      (DGT) sampling for Cu(II) by employing methylthymol blue as a chelating and
      chromogenic agent. Methylthymol blue was adsorbed onto beads of Dowex 1 x 8 resin
      (200-400 mesh) and the resin beads were then immobilised onto an adhesive disc.
      Analysis of exposed binding discs by either UV-vis spectrophotometry or computer
      imaging densitometry provided robust quantification of adsorbed Cu(II) in the 0.2
      1 microg cm(-2) range, allowing detection at microg L(-1) concentrations in the
      test solution (ca. 17 microg L(-1) for a 24 h deployment), and in good agreement
      with established DGT theory. The method was shown to be a potential replacement
      for binding phases based on Chelex 100 where a colorimetric response to a
      specific metal is desired.

PMID- 20152265
TI  - Novel approaches in analysis of Fusarium mycotoxins in cereals employing ultra
      performance liquid chromatography coupled with high resolution mass spectrometry.
AB  - Rapid, simple and cost-effective analytical methods with performance
      characteristics matching regulatory requirements are needed for effective control
      of occurrence of Fusarium toxins in cereals and cereal-based products to which
      they might be transferred during processing. Within this study, two alternative
      approaches enabling retrospective data analysis and identification of unknown
      signals in sample extracts have been implemented and validated for determination
      of 11 major Fusarium toxins. In both cases, ultra-high performance liquid
      chromatography (U-HPLC) coupled with high resolution mass spectrometry (HR MS)
      was employed. (13)C isotopically labeled surrogates as well as matrix-matched
      standards were employed for quantification. As far as time of flight mass
      analyzer (TOF-MS) was a detection tool, the use of modified QuEChERS (quick easy
      cheap effective rugged and safe) sample preparation procedure, widely employed in
      multi-pesticides residue analysis, was shown as an optimal approach to obtain low
      detection limits. The second challenging alternative, enabling direct analysis of
      crude extract, was the use of mass analyzer based on Orbitrap technology. In
      addition to demonstration of full compliance of the new methods with Commission
      Regulation (EC) No. 401/2006, also their potential to be used for confirmatory
      purposes according to Commission Decision 2002/657/EC has been critically
      assessed.

PMID- 20152266
TI  - Simultaneous determination of aflatoxins B1, B2, G1, G2, M1 and M2 in peanuts and
      their derivative products by ultra-high-performance liquid chromatography-tandem
      mass spectrometry.
AB  - A reliable ultra-high-performance liquid chromatography-tandem mass spectrometry
      (UHPLC-MS/MS) method for simultaneous determination of aflatoxins B1, B2, G1, G2,
      M1 and M2 in peanuts and their derivative products was developed. The sample was
      extracted by 84% of acetonitrile aqueous solution and the extract was purified by
      a reliable solid phase extraction-based clean-up method. Then, the analytes were
      separated on Acquity UPLC HSS T3 column (100 mm x 2.1 mm, 1.8 microm particle
      size), and eluted with a mobile phase consisting of (A) water containing 0.1%
      formic acid and (B) acetonitrile/methanol (50/50, v/v). The separated compounds
      were detected with a Waters Micromass Quattro Ultima Pt tandem quadrupole mass
      spectrometer operating in positive electro-spray ionization using multiple
      reaction monitoring mode. The established method was extensively validated by
      determining the linearity (R(2) > or = 0.9990), average recovery (74.7-86.8%) and
      precision (relative standard deviation < or = 10.9%). It was shown to be a
      suitable method for simultaneous determination of the six aflatoxins in peanuts
      and their derivative products. Finally, a total of 73 samples randomly collected
      from different areas in Zhejiang province were screened for aflatoxins with the
      proposed method. The results showed that 31 samples of peanut butter, 14 samples
      of fresh peanut and 5 samples of musty peanut were contaminated with aflatoxins.
      Meanwhile, this was the first report on aflatoxins M1 and M2, which were found in
      unprocessed peanuts and their derivative products.

PMID- 20152267
TI  - Screening and determination of melamine residues in tissue and body fluid
      samples.
AB  - Melamine is a chemical product that was sporadically mixed into animal feeds to
      boost protein content. Excessive melamine in animal feed can induce renal failure
      and even death in animals. The residue of melamine in edible animal products also
      threatens human health. Currently, there is no real-time and high throughput
      method to detect residual melamine in animal tissues. Successful development of
      such methods is very important for fast and on-site screening of melamine residue
      in animal tissues to eliminate the potential threat to human health. Here we
      demonstrate the detection of residual melamine from swine and chicken tissues and
      body fluids using indirect competitive enzyme-linked immunosorbent assay (ELISA)
      method. A detection sensitivity of 0.5 microg mL(-1) and a limit of detection of
      0.05 microg mL(-1) were achieved with this method. A gas chromatography-mass
      spectrometry (GC-MS) method was also developed to act as a confirmatory and
      quantitative procedure for the ELISA results. The limits of quantitation (LOQ) of
      were 0.01 microg g(-1) and 0.005 microg mL(-1) for tissues and body fluids,
      respectively. The two methods showed good agreement (r(2)>0.992). The method
      developed was performed on samples of tissues from chickens fed with melamine
      spiked feed.

PMID- 20152268
TI  - A selective and sensitive carbon composite coated platinum electrode for
      aluminium determination in pharmaceutical and mineral water samples.
AB  - A novel coated wire electrode (CWE) for Al(III) ions is described based on 2-(1H
      benzo[d]imidazole-1-yl)-1-phenylethanoneoxime as a new ionophore in carbon-PVC
      composite. The sensor exhibits significantly enhanced selectivity toward Al(3+)
      ions over the concentration range 4.3 x 10(-7) to 5.0 x 10(-2)M with a lower
      detection limit of 2.5 x 10(-7) M and a Nernstian slope of 19.41+/-0.52 mV
      decade(-1) of aluminium activity. This sensor has a short response time of about
      10s and is reproducible and stable for at least forty-five days. This proposed
      CWE which is designed for the first time revealed good selectivity for Al(III)
      over a wide variety of other cations. The performance of the sensor is best in
      the pH range of 3.1-5.5 and it also works well in partially non-aqueous medium.
      Moreover, the assembly has been successfully used as an indicator electrode in
      the potentiometric titration of aluminium (III) against EDTA and also in
      determining Al(III) quantitatively in pharmaceutical and mineral water samples.

PMID- 20152269
TI  - Evaluation of the feasibility of the electronic tongue as a rapid analytical tool
      for wine age prediction and quantification of the organic acids and phenolic
      compounds. The case-study of Madeira wine.
AB  - A set of fourteen Madeira wines comprising wines produced from four Vitis
      vinifera L. varieties (Bual, Malvasia, Verdelho and Tinta Negra Mole) that were
      3, 6, 10 and 17 years old was analysed using HPLC and an electronic tongue (ET)
      multisensor system. Concentrations of 24 organic acids, phenolic and furanic
      compounds were determined by HPLC. The ET consisting of 26 potentiometric
      chemical sensors with plasticized PVC and chalcogenide glass membranes was used.
      Significance of the effects of age and variety on the ET response and wine
      composition with respect to the organic acids, phenolics and furanic derivatives
      were evaluated using ANOVA-Simultaneous Component Analysis (ASCA). Significance
      of the effects was estimated using a permutation test (1000 permutations). It was
      found that effects of age, grape variety and their interaction were significant
      for the HPLC data set and only the effect of age was significant for the ET data.
      Calibration models of the HPLC and ET data with respect to the wine age and of
      the ET data with respect to the concentration of the organic acids and phenolics
      were calculated using PLS1 regression. Models were validated using cross
      validation. It was possible to predict wine age from HPLC and ET data with the
      accuracy in cross-validation of 2.6 and 1.8 years respectively. The ET was
      capable of detecting the following components (mean relative error in cross
      validation is shown in the parentheses): tartaric (8%), citric (5%), formic
      (12%), protocatehuic (5%), vanillic (18%) and sinapic (14%) acids, catechin (6%),
      vanillin (12%) and trans-resveratrol (5%). The ET capability of predicting
      Madeira wine age with good accuracy (1.8 years) as well as quantify of some
      organic acids and phenolic compounds was demonstrated.

PMID- 20152270
TI  - Single-walled carbon nanotubes as solid-phase microextraction adsorbent for the
      determination of low-level concentrations of butyltin compounds in seawater.
AB  - Carbon nanotubes are a kind of new carbon-based nanomaterials, which have drawn
      great attention in many application fields. The potential of single-walled carbon
      nanotubes (SWCNTs) as solid-phase microextraction (SPME) adsorbent for the
      preconcentration of environmental pollutants has been investigated in recent
      years. In the present study, the feasibility of SWCNTs as SPME adsorbent for the
      determination of monobutyltin, dibutyltin and tributyltin in seawater samples was
      studied. To achieve this aim, the potential factors affecting the SPME
      efficiency, including extraction time, extraction temperature, desorption time,
      desorption temperature, and salinity were optimized. The developed method showed
      good performance according to the ICH (International Conference on Harmonization
      of Technical Requirements for Analytical Methods) criteria. The acquired
      calibration curves were linear (r > or = 0.992) over the concentration range from
      < or = 12 to 2000 ng L(-1). For all of the analytes, the limit of detection at
      signal-to-noise ratio of 3 was below 5 ng L(-1). Furthermore, in comparison with
      the commercial carboxen/polydimethylsiloxane fiber, the developed SWCNT fiber
      showed better thermal stability (over 350 degrees C) and longer life span (over
      150 times). The application of the proposed method in environmental analyses was
      shown by analyzing seawater samples from the harbors on the Persian Gulf for
      butyltin residues. Some of the butyltins were detected in the analyzed samples.
      Results of the present study demonstrate the feasibility of the SWCNTs as SPME
      adsorbent for the determination of butyltins in seawater samples.

PMID- 20152271
TI  - A simple and sensitive HPLC method for the simultaneous determination of eight
      bioactive components and fingerprint analysis of Schisandra sphenanthera.
AB  - A simple and sensitive high performance liquid chromatography method with
      photodiode array detection (HPLC-DAD) was developed for simultaneous
      determination of eight bioactive constituents (schisandrin, schisandrol B,
      schisantherin A, schisanhenol, anwulignan, deoxyshisandrin, schisandrin B and
      schisandrin C) in the ripe fruit of Schisandra sphenanthera and its traditional
      Chinese herbal preparations Wuzhi-capsule by optimizing the extraction,
      separation and analytical conditions of HPLC-DAD. The chemical fingerprint of S.
      sphenanthera was established using raw materials of 15 different origins in
      China. The chromatographic separations were obtained by an Agilent Eclipse XDB
      C18 reserved-phase column (250 mm x 4.6 mm i.d., 5 microm) using gradient elution
      with water-formic acid (100:0.1, v/v) and acetonitrile, at a flow rate of 1.0 mL
      min(-1), an operating temperature of 35 degrees C, and a wavelength of 230 nm.
      The constituents were confirmed by (+) electrospray ionization LC-MS. The new
      method was validated and was successfully applied to simultaneous determination
      of components in 13 batches of Wuzhi-capsule. The results indicate that this
      multi-component determination method in combination with chromatographic
      fingerprint analysis is suitable for quantitative analysis and quality control of
      S. sphenanthera.

PMID- 20152272
TI  - Lesion size is a major determinant of the mammographic features of ductal
      carcinoma in situ: findings from the Sloane project.
AB  - AIM: To assess the radiological features of calcific ductal carcinoma in situ
      (DCIS) in a large, multicentre dataset according to grade and size, and to
      investigate the possibility that DCIS has different mammographic features when
      small. MATERIALS AND METHODS: The dataset consisted of all Sloane Project DCIS
      cases where calcification was present mammographically and histological grade and
      size were available. The radiology data form classifies calcific DCIS as
      casting/linear, granular/irregular, or punctate. The pathology dataset includes
      cytonuclear grade and microscopic tumour size. Correlations were sought between
      the radiological findings and DCIS grade and size. The significance of
      differences was assessed using the chi-square test and chi-square test for trend.
      RESULTS: One thousand, seven hundred and eighty-three cases were included in the
      study. Of these, 1128, 485, and 170 had high, intermediate, and low-grade DCIS,
      respectively. Casting calcification was more frequently seen the higher the grade
      of DCIS, occurring in 58% of high grade, 38% of intermediate grade, and 26% of
      low-grade cases, respectively (p<0.001). Casting calcification was also
      increasingly common with increasing lesion size, irrespective of the histological
      grade (p<0.001). Thus casting calcifications in small (<10mm) high-grade DCIS
      lesions were seen with a similar frequency (50%) to those in moderate-sized (21
      30 mm) intermediate-grade lesions (48%), and to those in large (>30 mm) low-grade
      lesions (46%). CONCLUSION: Lesion size has a strong influence on the radiological
      features of calcific DCIS; small, high-grade lesions often show no casting
      calcifications, whereas casting calcifications are seen in nearly half of large,
      low-grade lesions. As small clusters of punctate or granular calcifications may
      represent high-grade DCIS, an aggressive clinical approach to the diagnosis of
      such lesions is recommended as the adequate treatment of high-grade DCIS will
      prevent the occurrence of potentially life-threatening high-grade invasive
      disease.

PMID- 20152273
TI  - MR urography versus retrograde pyelography/ureteroscopy for the exclusion of
      upper urinary tract malignancy.
AB  - AIM: To evaluate the diagnostic performance of magnetic resonance urography (MRU)
      versus retrograde pyelography and/or ureteroscopy (RPU) in the detection of upper
      urinary tract neoplasms. MATERIALS AND METHODS: This retrospective study included
      35 patients with suspected upper urinary tract malignancy who underwent MRU and
      RPU within 6-months in our institution during the study period (February 2002 to
      January 2007). MRU and RPU reports were reviewed and results recorded. For each
      patient, the urinary tract was sub-divided into four regions for analysis: left
      kidney/renal pelvis, left ureter, right kidney/renal pelvis, and right ureter.
      MRU and RPU results for each patient were compared to a reference standard and
      the diagnostic performance of both techniques was compared. RESULTS: A total of
      113 regions were analysed on MRU and 90 regions on RPU. Nineteen neoplasms were
      identified. Sensitivity, specificity, positive predictive value, and negative
      predictive value for the detection of urinary tract neoplasms were 63, 91, 60,
      and 92% for MRU, respectively, and 53, 97, 83, and 88% for RPU, respectively.
      These differences were not statistically significant (p>0.05). CONCLUSION: The
      high negative predictive value of MRU in the present series supports its use as a
      non-invasive screening examination for excluding the presence of upper urinary
      tract malignancy.

PMID- 20152274
TI  - Optimal reconstructed section thickness for the detection of liver lesions with
      multidetector CT.
AB  - AIM: To evaluate the impact of different reconstructed section thicknesses on
      liver lesion detection using multidetector computed tomography (CT). METHODS:
      Fifty-three patients were examined using a 16-section CT machine with axial
      reconstructions provided at 2.5, 5, 7.5, and 10mm section thicknesses. Images of
      different reconstructed section thicknesses from different patients were
      presented in random order to three independent, blinded radiologists for review
      at multiple sessions. All images were then reviewed by three radiologists in a
      common session. Consensus was reached following review of the previous
      interpretation results and results of follow-up imaging regarding the number of
      true liver lesions (n=101) for comparison. RESULTS: Mean detection rates were as
      follows: 93/101 lesions detected with the 2.5mm section thickness, 98/101 lesions
      detected at the 5mm section thickness, 78/101 lesions detected at the 7.5mm
      section thickness, and 54/101 lesions detected at the 10mm section thickness.
      Lesions missed at the 2.5mm section thickness were due to masking by image noise.
      There was particular difficulty detecting subcapsular lesions and lesions
      adjacent to fissures or the gall bladder at the 7.5mm and 10mm section
      thicknesses. CONCLUSION: The optimal reconstructed section thickness for lesion
      detection in the liver was 5mm.

PMID- 20152275
TI  - Screening for breast cancer post reduction mammoplasty.
AB  - AIM: To investigate whether remodelling of the breast after breast reduction
      surgery has an effect on mammographic cancer detection. METHODS AND MATERIALS:
      For women who attended population-based screening between January 1998 to
      December 2007, data were extracted on their age, history of previous breast
      reduction, and the result of screening (recall for further assessment, cancer, or
      no cancer). The number of cancers detected, recalls per 1000 screens and the
      characteristics of the cancers detected in the two groups was compared. RESULTS:
      In total 244,147 women with 736,219 screening episodes were reviewed. In the 4743
      women who had a breast reduction, 51 breast cancers were detected [age
      standardized rate (ASR) of 4.28 per 1000 screening episodes; 95% CI 3.11-5.46],
      compared with 4342 breast cancers in 239 404 women screened in the non-reduction
      group (ASR of 5.99 per 1000 screening episodes; 95% CI 5.81-6.16). There were
      fewer cancers in the breast reduction group with a relative risk of 0.71. There
      was no significant difference in the rate of recall between the two groups, with
      a crude recall rate of 46.1 per 1000 screening episodes post-breast reduction
      compared with 50.7 per 1000 screening episodes for women without breast
      reduction. There was no significant difference in the pathological type or
      location of the cancer between the two groups of women. CONCLUSION: Postoperative
      breast changes following reduction mammoplasty do not significantly hinder
      analysis of the screening mammogram.

PMID- 20152276
TI  - Computed tomography in left-sided and right-sided blunt diaphragmatic rupture:
      experience with 43 patients.
AB  - AIM: To investigate differences in the radiographic signs for left and right
      sided blunt diaphragmatic rupture (BDR) in order to provide guidance to avoid
      missing these injuries. MATERIALS AND METHODS: A retrospective review of the
      computed tomography (CT) examinations of 43 patients with BDR treated at our
      hospital between January 1995 and 2007 was undertaken. The presence of
      diaphragmatic discontinuity, diaphragmatic thickening, herniation of abdominal
      organs into the thoracic cavity, collar/hump sign, dependent viscera sign,
      abnormally elevated 4 cm or more above the dome of the other-sided hemi
      diaphragm, and of associated injuries was recorded and their relationship to each
      other and to BDR diagnosis examined. A comparison between the use of axial and
      sagittal/coronal reconstruction images in diagnosis was also performed in 15
      patients. RESULTS: On axial imaging, left-sided diaphragmatic rupture occurred in
      31 patients (72%) and right-sided in 12 (28%). Twenty-nine patients had
      associated injuries. More than 60% of the patients showed the "dependent viscera"
      sign, "abdominal organ herniation" sign, diaphragm thickening, or had a more than
      4 cm elevation of one side of the diaphragm. "Diaphragmatic discontinuity" and
      "stomach herniation" were seen almost exclusively in left-sided rupture. Those
      with BDR and haemothorax had a significantly lower incidence of "diaphragm
      discontinuity" (p=0.034) than those without haemothorax. Sagittal/coronal
      reconstruction slightly increased the number of band signs, diaphragmatic
      discontinuities and diaphragmatic thickenings seen. CONCLUSIONS: Of the CT signs
      examined in this study, when herniation of abdominal organs was used as a
      diagnostic marker, only a very small fraction of trauma patients identifiable by
      CT would be missed. Further, CT signs differ for left-sided and right-sided BDR,
      thus the possibility of BDR should be considered when any of the reported CT
      signs are present.

PMID- 20152277
TI  - A comparative review of multidetector CT angiography and MRI in the diagnosis of
      jugular foramen lesions.
AB  - AIM: To compare the efficiency of multidetector computed tomography (MDCT) and
      magnetic resonance imaging (MRI) in the diagnosis of jugular foramen lesions.
      MATERIALS AND METHODS: The imaging of 15 patients with tumours predominantly
      occurring at the jugular foramen was retrospectively reviewed, with postoperative
      pathology data available for 11 patients. MDCT was performed at arterial phase
      and MRI with standard sequences and contrast enhancement. All imaging was blindly
      re-reported by an experienced neuroradiologist. RESULTS: Pathology reported six
      glomus jugulare tumours and five neuromas, which were all correctly diagnosed
      using MDCT. A confident diagnosis was also made in the remaining four cases based
      on the pattern of enhancement. Only glomus tumours enhanced in the arterial
      phase. Overall, MRI was used to make a confident diagnosis in eight patients. One
      showed no enhancement and was correctly diagnosed as a neuroma, and seven
      demonstrated the tumour flow voids characteristic of a glomus tumour. The
      remaining seven cases all showed a similar enhancement pattern and could not be
      confidently differentiated between a neuroma or a glomus tumour. MDCT angiography
      enabled a confident assessment of the jugular vein in all cases, but MRI was
      inconclusive in a third of cases. Also, in the nine cases of glomus tumour
      diagnosed using MDCT, an enlarged feeding artery was identified in eight
      patients. CONCLUSION: MDCT is more accurate than MRI in diagnosing glomus
      tumours, and in particular, neuromas. It also offers valuable preoperative
      vascular information to the surgeon.

PMID- 20152278
TI  - Criteria for the safe avoidance of needle sampling in young women with solid
      breast masses.
AB  - AIM: To establish clinical and ultrasonic criteria by which needle sampling can
      be safely avoided in young women with solid breast masses. MATERIALS AND METHODS:
      The databases of a large hospital were searched for breast cancers, phyllodes
      tumours, and papillomas diagnosed in women below the age of 30 years. In
      addition, the clinical and sonographic findings in female patients less than 25
      years of age presenting with a solid breast mass over a 1-year period were
      reviewed. RESULTS: Nine women with breast cancer, seven with phyllodes, and six
      with papillomas were found. No delayed diagnoses in those who had ultrasound
      would have been made if the following criteria had been applied to avoid needle
      sampling: age less than 25 years; no known risk factors for breast malignancy;
      mass not rapidly enlarging; smooth discrete mobile mass on clinical examination,
      or lesion impalpable; well-defined homogeneously isoechoic or mildly hypoechoic
      solid mass; less than 3 cm in greatest dimension; ovoid shape, aligned parallel
      to the skin surface; smooth or gently lobulated contour (two or three lobulations
      only; no microlobulation); thin echogenic pseudocapsule; no calcification; no
      acoustic shadowing. Needle sampling could have been safely avoided in
      approximately two-thirds of the women reviewed below the age of 25 with a solid
      breast mass. CONCLUSION: Application of the proposed criteria would spare a
      significant number of young women unnecessary needle sampling.

PMID- 20152279
TI  - CT and MRI features of acinar cell carcinoma of the pancreas with pathological
      correlations.
AB  - AIM: To document the computed tomography (CT) and magnetic resonance imaging
      (MRI) features of acinar cell carcinoma of the pancreas and to correlate them
      with pathological findings to determine the unique imaging manifestations of this
      rare subtype tumour of the pancreas. MATERIALS AND METHODS: From January 1986 to
      August 2008, six patients (five men and one woman, mean age 61.3 years) with
      histologically proven acinar cell carcinoma of the pancreas underwent CT (n=6)
      and MRI (n=4) examinations. The imaging features of each tumour were documented
      and compared with pathological findings. RESULTS: The tumours were distributed in
      the head (n=4), body (n=1), and tail (n=1) of the pancreas. Four masses (67%)
      were uniformly or partially well-defined with thin, enhancing capsules. Central
      cystic components were found in five tumours (83%). Two tumours (33%) exhibited
      intratumoural haemorrhage, and one tumour (17%) had amorphous intratumoural
      calcification. In both CT and MRI, the tumours enhanced less than the adjacent
      normal pancreatic parenchyma. The signal intensity on MRI was predominantly T1
      hypointense and T2 iso- to hyperintense. CONCLUSION: Acinar cell carcinoma of the
      pancreas has distinct imaging features, and both CT and MRI are useful and
      complementary imaging methods.

PMID- 20152280
TI  - Radiofrequency ablation of kidney tumours in patients with a solitary kidney.

PMID- 20152281
TI  - What's in a name? Eponyms in head and neck imaging.
AB  - Head and neck (H&N) eponyms serve to honour physicians who have made important
      contributions. Compared with more descriptive diagnostic names, eponyms can
      sometimes be confusing, especially to the novice. Adding to the confusion,
      eponyms are sometimes applied incorrectly. Nevertheless, their use remains common
      in the medical literature and clinical practice. Familiarity with H&N eponyms is
      important for accurate communication with radiology colleagues and clinicians.
      Some eponyms describe potentially fatal infections and their urgency should be
      appreciated. Other eponyms, such as those for inner ear congenital anomalies, are
      probably best avoided as they can be used imprecisely and cause confusion. This
      review summarizes the clinical and imaging findings of some common and important
      H&N eponyms under the following categories of disease: (1) neck infections, (2)
      diseases in the temporal bone, (3) orbital diseases, and (4) sinus disease.

PMID- 20152282
TI  - MRI appearance of internal hernia following Roux-en-Y gastric bypass surgery in
      the pregnant patient.

PMID- 20152283
TI  - Erdheim-Chester disease presenting with destruction of a metacarpal.

PMID- 20152284
TI  - Ectopic insertion of the pectoralis minor muscle with tendinosis as a cause of
      shoulder pain and clicking.

PMID- 20152285
TI  - RE: CT before lumbar puncture in meningitis--what every radiology trainee should
      know.

PMID- 20152288
TI  - Prenatal exposure to tobacco and risk for schizophrenia: a retrospective
      epidemiological study.
AB  - INTRODUCTION: In animal studies, long-term prenatal nicotinic exposure alters the
      development of dopaminergic neurons. To determine whether prenatal smoking
      exposure was associated with schizophrenia, using a retrospective design study,
      we compared the prevalence of tobacco use during pregnancy in mothers of subjects
      with and without schizophrenia. METHODS: One hundred patients with schizophrenia,
      100 nonschizophrenic-matched subjects, and their respective mothers were
      interviewed. The prevalence of smoking was measured in these individuals as well
      as in their respective mothers during the pregnancy. RESULTS: Patients with
      schizophrenia smoked more often compared with controls (73% vs 57%). In contrast,
      the prevalence of smoking during pregnancy did not differ between the groups of
      mothers. Indeed, the amount of tobacco used was significantly lower in mothers of
      patients with schizophrenia vs mothers of nonpsychotic subjects. CONCLUSION: This
      study did not show any association between prenatal tobacco exposure and further
      development of schizophrenia.

PMID- 20152287
TI  - Clinical characteristics of depressed outpatients previously overdiagnosed with
      bipolar disorder.
AB  - The diagnosis of bipolar disorder in depressed patients requires the
      ascertainment of prior episodes of mania and hypomania. Several research reports
      and commentaries have suggested that bipolar disorder is underrecognized and that
      many patients with nonbipolar major depressive disorder have, in fact, bipolar
      disorder. In a previous article from the Rhode Island Methods to Improve
      Diagnostic Assessment and Services (MIDAS) project, we reported the opposite
      phenomenon-that bipolar disorder is often overdiagnosed in psychiatric
      outpatients. An important question that has not been previously examined is
      whether there is a particular clinical or demographic profile associated with
      bipolar disorder overdiagnosis among depressed patients. Forty psychiatric
      outpatients with current major depressive disorder reported having been
      previously diagnosed with bipolar disorder, which was not confirmed when
      interviewed with the Structured Clinical Interview for Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (SCID). Psychiatric diagnoses,
      clinical and demographic variables were compared in these 40 patients and 233
      depressed patients who were not diagnosed with bipolar disorder. Patients were
      interviewed by a highly trained diagnostic rater who administered the SCID for
      DSM-IV Axis I disorders, the Structured Interview for DSM-IV Personality for DSM
      IV Axis II disorders, and the Schedule for Affective Disorders and Schizophrenia
      for clinical features of depression. The depressed patients who were
      overdiagnosed with bipolar disorder were diagnosed with a significantly higher
      number of Axis I disorders and were more likely to be diagnosed with specific
      phobia, posttraumatic stress disorder, and drug abuse/dependence. The patients
      overdiagnosed with bipolar disorder were also significantly more likely to be
      diagnosed with a current personality disorder and were more chronically ill with
      greater psychosocial impairment. Thus, the results suggest that depressed
      outpatients who had previously been overdiagnosed with bipolar disorder were more
      chronically and severely ill than depressed outpatients who had not been
      overdiagnosed.

PMID- 20152289
TI  - Impact of binge eating disorder in the psychopathological profile of obese women.
AB  - OBJECTIVE: Our objective was to evaluate the psychopathological profile of obese
      women with binge eating disorder (BED) using the Symptom Checklist-90 (SCL-90).
      METHODS: Two hundred twelve obese women who seek for weight loss treatment were
      sequentially selected to participate in the study. Binge eating disorder was
      diagnosed using the Structured Clinical Interview for Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition. Binge eating disorder severity was
      assessed using Binge Eating Scale. Depressive symptoms were assessed using Beck
      Depression Inventory. The psychopathological profile was assessed using the SCL
      90. RESULTS: Binge eating disorder was diagnosed in 54 patients (26.6%). Obese
      patients with BED presented significant higher scores in all domains of SCL-90 (P
      < .05 for all) in comparison with obese patients without BED. A significant
      relationship was found among Binge Eating Scale, Beck Depression Inventory, and
      all domains of the SCL-90 (P < .05 for all). After linear regression, obsessivity
      compulsivity (P = .03), interpersonal sensitivity (P = .0064), paranoid ideas (P
      = .03), and psychoticism (P = .01) were independently related to the severity of
      BED. CONCLUSION: Obese women with BED presented a more severe psychopathological
      profile than obese controls. Among all, obsessivity-compulsivity, interpersonal
      sensitivity, paranoid ideas, and psychoticism seem to be strongly linked to BED
      severity.

PMID- 20152291
TI  - Is impulsivity a link between childhood abuse and suicide?
AB  - Childhood abuse and neglect are known to affect psychological states through
      behavioral, emotional, and cognitive pathways. They increase the risk of having
      psychiatric diseases in adulthood and have been considered risk factors for
      suicidal behavior in all diagnostic categories. Early, prolonged, and severe
      trauma is also known to increase impulsivity, diminishing the capacity of the
      brain to inhibit negative actions and to control and modulate emotions. Many
      neurobiological studies hold that childhood maltreatment may lead to a persistent
      failure of the inhibitory processes ruled mainly by the frontal cortex over a
      fear-motivated hyperresponsive limbic system. Multiple neurotransmitters and
      hormones are involved in the stress response, but, to our knowledge, the two
      major biological consequences of the chronic exposure to trauma are the
      hypofunction of the serotonergic system and changes in the hypothalamic-pituitary
      adrenal axis function. Some of these findings overlap with the neurobiological
      features of impulsivity and of suicidal behavior. Impulsivity has also been said
      to be both a consequence of trauma and a risk factor for the development of a
      pathological response to trauma. Thus, we suggest that impulsivity could be one
      of the links between childhood trauma and suicidal behavior. Prevention of
      childhood abuse could significantly reduce suicidal behavior in adolescents and
      adults, in part, through a decrease in the frequency of impulsive behaviors in
      the future.

PMID- 20152290
TI  - Pathologic gambling and bankruptcy.
AB  - BACKGROUND: Although prior studies have examined rates of bankruptcy in
      pathologic gambling (PG), there are only limited data regarding the clinical
      correlates of those with PG who declare bankruptcy because of gambling. METHOD:
      Five hundred seventeen consecutive subjects with Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, PG (54.7% females; mean age 47.6
      years) were grouped into 2 categories: those who had (n = 93; 18.0%) and had not
      (n = 424; 82.0%) declared bankruptcy secondary to gambling. Groups were compared
      on clinical characteristics, gambling severity (using the Yale-Brown Obsessive
      Compulsive Scale Modified for Pathological Gambling, Gambling Symptom Assessment
      Scale; Clinical Global Impression-severity scale, and time and money spent
      gambling), and psychiatric comorbidity. RESULTS: Gamblers who had declared
      bankruptcy were more likely to be single (P = .004); have an earlier age of
      problem gambling onset (P = .032); and have more financial (P < .001), work
      related (P = .006), marital (P < .001), and legal (P < .001) problems secondary
      to their gambling. They also reported higher rates of depressive disorders (P <
      .001), substance use disorders (P = .005) and were more likely to be daily users
      of nicotine (P = .022). Money spent gambling did not differ significantly between
      groups. CONCLUSION: These preliminary results suggest that bankruptcy in PG may
      be associated with specific clinical differences. Treatment strategies may want
      to assess bankruptcy status to develop more effective treatments that take
      account of these clinical differences.

PMID- 20152292
TI  - Monoamine oxidase A genotype is associated with gang membership and weapon use.
AB  - CONTEXT: A functional polymorphism in the promoter region of the monoamine
      oxidase A (MAOA) gene has been found to be associated with a broad range of
      antisocial phenotypes, including physical violence. At the same time, it is well
      known that gang members represent some of the most serious violent offenders.
      Even so, no research has ever examined the association between MAOA and gang
      membership. OBJECTIVES: The aim of this study is to examine the association
      between MAOA and gang membership and between MAOA and weapon use. DESIGN: We
      examined the effects of MAOA by using a molecular genetic association research
      design. SETTING: A nonclinical sample was used in this study. PARTICIPANTS:
      Participants were drawn from the National Longitudinal Study of Adolescent Health
      (1155 females, 1041 males). MAIN OUTCOME MEASURES: The outcome measures of this
      study are gang membership and weapon use. RESULTS: The low MAOA activity alleles
      conferred an increased risk of joining a gang and using a weapon in a fight for
      males but not for females. Moreover, among male gang members, those who used
      weapons in a fight were more likely to have a low MAOA activity allele when
      compared with male gang members who do not use weapons in a fight. CONCLUSIONS:
      Male carriers of low MAOA activity alleles are at risk for becoming a gang member
      and, once a gang member, are at risk for using weapons in a fight.

PMID- 20152293
TI  - Perpetrators of homicide with schizophrenia: sociodemographic characteristics and
      clinical factors in the eastern region of Turkey.
AB  - In this study, we aimed to describe the social and clinical characteristics and
      offense details in a sample of people with schizophrenia convicted of homicide in
      the eastern region of Turkey. This study was performed in Elazig Mental Hospital
      between November 2004 and May 2007. We included 43 men and 6 women with
      schizophrenia convicted of homicide who were hospitalized in the forensic
      psychiatry unit for compulsory treatment. Preset data recording forms were used.
      The first part of the forms contained questions regarding the age, sex, marital
      status, residence, educational status, and occupation of the patients. The second
      part of the forms included questions about some clinical features of patients
      with schizophrenia: the presence of schizophrenia in any family member, duration
      of the disease, subtype of schizophrenia, previous contact with mental health
      services, types of antipsychotics (first and last drug used), and adherence to
      antipsychotic medication. The third part of the forms dealt with alcohol
      substance abuse and features of the victim (sex of the victim and whether the
      victim was a stranger, partner, or an ex-partner in the family or an
      acquaintance). The mean +/- SD age of our patients was 36.98 +/- 10.07 years, and
      55.1% of the patients were unmarried. In our sample, 42.9% of the patients were
      primary school graduates and 75.5% were unemployed. Of the perpetrators, 14.3%
      never had contact with mental health services. However, 85.7% of patients had
      previous contact with mental health services. We found that 85.7% of the patients
      were paranoid subtype and 85.7% were not using their medication regularly and
      that treatment compliance was considerably low. We found that haloperidol and
      trifluoperazine were the most preferred antipsychotic drugs, particularly being
      the first drugs used during treatment (haloperidol, 71.4%; trifluoperazine,
      10.2%) and the last antipsychotics used before the offence (haloperidol, 46.9%;
      trifluoperazine, 20.4%). In 38.8% of cases, schizophrenia was present in the
      first-degree relatives. We also found that 69.4% of victims were one of the
      family members. In our sample, 24.5% of patients were using alcohol and 4.1% were
      using cannabis. It is plausible that rendering more effective communication might
      allow earlier intervention for unrecognized and possibly unrecognizable risk
      factors of homicidal acts in people with schizophrenia.

PMID- 20152295
TI  - Mortality in Kraepelinian schizophrenic patients: a prospective study with a
      median follow-up of 8.4 years.
AB  - Kraepelinian schizophrenia is a subtype of schizophrenia defined by its very poor
      outcome. Several studies have demonstrated the validity of this distinction, but
      the expected excess mortality has not been investigated. The aim of the present
      study was to test the hypothesis that Kraepelinian schizophrenic subjects have a
      higher mortality rate, notably due to natural causes, than non-Kraepelinian
      schizophrenic subjects. The results of a prospective study with a median follow
      up of 8.4 years are reported. Three hundred ten schizophrenic subjects meeting
      the International Classification of Diseases, 10th Revision, criteria for
      schizophrenia were classified on admission as Kraepelinian schizophrenia (n = 31)
      and non-Kraepelinian schizophrenia (n = 279); 31 deaths (16 from unnatural
      causes, 13 from natural causes, and 2 from undetermined causes) were observed
      during follow-up. Univariate and multivariate Cox regression analyses were
      performed using schizophrenia subtype (Kraepelinian vs non-Kraepelinian), age,
      and duration of illness as predictors. Schizophrenia subtype was a significant
      predictor of mortality in univariate analysis only for death from natural causes,
      and a trend was observed after adjusting for age and duration of illness. A log
      rank test was used to compare mortality rates between Kraepelinian and non
      Kraepelinian schizophrenic subjects and showed a significantly higher mortality
      rate from natural causes in Kraepelinian schizophrenia (16.7%) than in non
      Kraepelinian schizophrenia (4.1%).

PMID- 20152294
TI  - Eating disorder psychopathology as a marker of psychosocial distress and suicide
      risk in female and male adolescent psychiatric inpatients.
AB  - OBJECTIVE: The aim of this study was to examine psychosocial correlates of
      specific aspects of eating disorder (ED) psychopathology (ie, dietary
      restriction, body dissatisfaction, binge eating, and self-induced vomiting) in
      psychiatrically hospitalized adolescent girls and boys. METHOD: A total of 492
      psychiatric inpatients (286 adolescent girls and 206 adolescent boys), aged 12 to
      19 years, completed self-report measures of psychosocial and behavioral
      functioning, including measures of suicide risk and ED psychopathology.
      Associations between ED psychopathology and psychosocial functioning were
      examined separately by sex and after controlling for depressive/negative affect
      using Beck Depression Inventory scores. RESULTS: Among the adolescent boys and
      girls, after controlling for depressive/negative affect, ED psychopathology was
      significantly associated with anxiety, low self-esteem, and current distress
      regarding childhood abuse. Among adolescent girls, after controlling for
      depressive/negative affect, ED psychopathology was significantly related to
      hopelessness and suicidality. Among adolescent boys, after controlling for
      depressive/negative affect, ED psychopathology was positively related to self
      reported history of sexual abuse and various externalizing problems (drug abuse,
      violence, and impulsivity). CONCLUSION: In psychiatrically hospitalized
      adolescents, ED psychopathology may be an important marker of broad psychosocial
      distress and behavioral problems among girls and boys, although the nature of the
      specific associations differs by sex.

PMID- 20152296
TI  - A comparison of life events in patients with unipolar disorder or bipolar
      disorder and controls.
AB  - OBJECTIVE: The present study aimed to explore the association between stressful
      life events (LEs) and the development of affective psychopathology. METHOD:
      Thirty patients with unipolar disorder and 30 patients with bipolar disorder were
      compared to 60 matched healthy controls in regard to the rate of stressful LEs.
      Assessment measures included the Beck Depression Inventory, the Adult Life Events
      Questionnaire, and the Childhood Life Events List. RESULTS: The entire sample of
      affective patients had more LEs in general, more negative LEs, and more loss
      related LEs in the year preceding their first depressive episode as compared with
      normal controls. Subjects with unipolar disorder had more positive LEs and more
      achievement LEs, whereas subjects with bipolar disorder had more uncontrollable
      LEs in the year preceding the first depressive episode. The relationship between
      LEs and manic episodes was prominent in the year preceding the first manic
      episode, with subjects with bipolar disorder reporting more LEs in general and
      more ambiguous events in that year. Almost no significant differences on LE
      frequency were observed in the year before the last depressive and manic episodes
      in the patient groups with unipolar and bipolar disorder. A significant
      relationship was found between childhood LEs and the development of affective
      disorders in adulthood, with patients with unipolar disorder exhibiting less
      positive and achievement LEs. CONCLUSIONS: In both the unipolar and the bipolar
      groups, the major impact of LEs on the onset of affective disorders was found in
      the year before the first depressive or manic episodes. This suggests that the
      accumulation of stressful LEs at this crucial period contributes to the
      precipitation of a pathological response mechanism. Once established, this
      mechanism would be reactivated in the future by even less numerous and less
      severe stressors, compatible with the kindling hypothesis.

PMID- 20152297
TI  - The relationship between depressive symptoms and subjective well-being in newly
      admitted patients with schizophrenia.
AB  - BACKGROUND: Depressive symptoms are common in schizophrenia and are considered
      core features of the disorder. The purpose of the present study was to examine
      the relationship between depressive symptoms and subjective well-being in newly
      admitted patients with schizophrenia. METHODS: Eighty newly admitted patients
      were comprehensively evaluated for subjective well-being, schizophrenic symptoms,
      and depressive symptoms using the Subjective Well-Being Under Neuroleptics Scale
      (SWN), the Positive and Negative Syndrome Scale (PANSS), and the Beck Depression
      Inventory. Correlation coefficients were obtained between depressive symptoms and
      subjective well-being while controlling for the influence of the severity of
      psychotic symptoms, extrapyramidal side effect, and subjective attitude toward
      antipsychotics, as assessed by the PANSS, the Drug-Induced Extrapyramidal
      Symptoms Scale, and the Drug Attitude Inventory, respectively. RESULTS: The SWN
      score had a significant negative correlation with the PANSS depression factor
      score (P < .001). Correlation analysis also revealed a significant negative
      correlation between the SWN score and the Beck Depression Inventory score (P <
      .001). CONCLUSIONS: The results of our study suggest that depressive symptoms are
      significantly associated with a low subjective well-being in newly admitted
      patients with schizophrenia and that the relationship is significant even after
      controlling for the influence of potential confounding variables. Detection and
      appropriate management of depressive symptoms in schizophrenic patients may
      affect their perceptions of their own well-being.

PMID- 20152299
TI  - Delusional versus nondelusional body dysmorphic disorder.
AB  - This study assessed demographic and clinical features in 65 subjects with body
      dysmorphic disorder (BDD) and compared the 39 (60%) with the delusional form
      (receiving an additional diagnosis of delusional disorder, somatic type) with
      those who did not meet delusionality criteria. Delusional and nondelusional
      patients did not statistically differ on most demographic and clinical variables.
      Delusional patients, however, had significantly more severe BDD symptoms at both
      baseline and follow-up assessments than those of nondelusional patients.
      Furthermore, poorer insight was significantly associated with more severe BDD
      symptoms at both baseline and follow-up. Overall improvement in BDD symptom
      severity was similar for the 2 groups. Our results support other studies in the
      view that BDD and its delusional variant have more similarities than differences
      and that the delusional variant may be simply a more severe form of BDD.
      Implications for the diagnostic classification of BDD and future research
      directions are discussed.

PMID- 20152298
TI  - Current alcohol use and risk for hypomania in male students: generally more or
      more binging?
AB  - BACKGROUND: Alcohol use disorders and bipolar disorder are highly comorbid. Some
      studies suggest that alcohol abuse or misuse might even precede the onset of
      bipolar disorder, but few studies have looked at the daily drinking pattern
      beyond diagnostic categories. We therefore examined if risk for hypomania is
      associated with a specific drinking pattern when using a calendar-based
      interview. METHOD: A total of 120 students who completed the Hypomanic
      Personality Scale were independently interviewed with the FORM 90 to assess daily
      drinking and the Composite Diagnostic Interview to derive Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, diagnoses. RESULTS:
      Conducting regression analyses, we found that an alcohol-related disorder was
      related to the amount and frequency of drinking, as expected. Risk for hypomania
      was specifically related to an unstable drinking pattern and binge drinking, but
      not generally higher consumption. CONCLUSION: Risk for hypomania was associated
      with unstable alcohol consumption and binge drinking, even after controlling for
      alcohol-related disorders. This supports the idea that instability in different
      areas of behavior is characteristic of vulnerability to hypomania.

PMID- 20152300
TI  - The prevalence of pathologic skin picking in US adults.
AB  - OBJECTIVE: Despite increasing recognition of the potentially severe medical and
      psychosocial costs of pathologic skin picking (PSP), no large-sample, randomized
      investigation of its prevalence in a national population has been conducted.
      METHOD: Two thousand five hundred and thirteen US adults were interviewed during
      the spring and summer of 2004 in a random-sample, national household computer
      assisted phone survey of PSP phenomenology and associated functional impairment.
      Respondents were classified for subsequent analysis according to proposed
      diagnostic criteria. RESULTS: Of all respondents, 16.6% endorsed lifetime PSP
      with noticeable skin damage; 60.3% of these denied picking secondary to an
      inflammation or itch from a medical condition. One fifth to one quarter of those
      with lifetime PSP not related to a medical condition endorsed tension or
      nervousness before picking, tension or nervousness when attempting to resist
      picking, and pleasure or relief during or after picking. A total of 1.4% of our
      entire sample satisfied our criteria of picking with noticeable skin damage not
      attributable to another condition and with associated distress or psychosocial
      impairment. Pickers satisfying these latter criteria differed from other
      respondents in demographics (age, marital status) and both picking phenomenology
      and frequency.

PMID- 20152301
TI  - Distinguishing affective depersonalization from anhedonia in major depression and
      bipolar disorder.
AB  - BACKGROUND: Affective depersonalization has received limited attention in the
      literature, although its conceptualization may have implications in terms of
      identification of clinical endophenotypes of mood disorders. Thus, this study
      aims to test the hypothesis that anhedonia and affective depersonalization
      represent 2 distinct psychopathological dimensions and to investigate their
      clinical correlates in patients with major depressive disorder (MDD) and bipolar
      disorder (BD). METHODS: Using a data pool of 258 patients with mood and anxiety
      disorders, an item response theory-based factor analysis approach was carried out
      on 16 items derived from 2 clinical instruments developed in the Spectrum Project
      (the Structured Clinical Interview for Mood Spectrum and the Structured Clinical
      Interview for Derealization-Depersonalization Spectrum). Clinical correlates of
      these psychometrically derived dimensions were subsequently investigated in
      patients with BD or MDD. RESULTS: Using an item response theory-based factor
      analysis, a 2-factor solution was identified, accounting overall for the 47.0% of
      the variance. Patients with BD showed statistically significant higher affective
      depersonalization factor scores than those with MDD (Z = 2.215, P = .027),
      whereas there was no between-groups difference in anhedonia scores (Z = 0.825 P =
      .411). In patients with BD, age of onset of the disease correlated with affective
      depersonalization factor scores (rho = -0.330, P = .001) but not with anhedonia
      factor scores (rho = -0.097, P = .361). CONCLUSIONS: Affective depersonalization
      and anhedonia seem to be 2 distinct psychopathological dimensions, although
      closely related, bearing the opportunity to identify patients with a specific
      profile for a better clinical and neurobiological definition.

PMID- 20152302
TI  - Clinical predictors of health-related quality of life in obsessive-compulsive
      disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a serious mental disorder that
      has severe impact on a person's quality of life and those living with a person
      with OCD. This study systematically examined the clinical variables that are
      predictive of several domains of quality of life in a large, well-characterized
      sample of patients attending a specialized treatment unit in Italy. METHODS: The
      Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was administered
      to 151 patients with OCD and their scores were compared to published Italian
      norms. A principal component analysis was performed on the 13 major categories of
      the Yale-Brown Obsessive-Compulsive Scale (YBOCS) Symptom Checklist to derive
      symptom dimension scores. The association between various domains of quality of
      life and a wide range of clinical variables, including symptom dimension scores,
      was examined using multiple regression models. RESULTS: Compared to published
      Italian norms, patients with OCD showed impairment in most domains of quality of
      life, particularly social functioning. The principal component analysis of the
      YBOCS Symptom Checklist yielded 5 symptom dimensions that were identical to those
      previously identified in the international literature. Fewer years of education,
      higher depression scores (Hamilton Rating Scale for Depression), higher YBOCS
      obsessions scores, and higher scores on the contamination/washing symptom
      dimension independently predicted a poorer score on the physical health component
      of the SF-36. Higher YBOCS compulsions scores, the presence of a current mood
      disorder, and higher anxiety scores (Hamilton Rating Scale for Anxiety) predicted
      a poorer score on the mental health component of the SF-36. CONCLUSIONS: Our
      study confirms that quality of life is severely impaired in patients with OCD.
      The identification of predictors of quality of life in OCD can help clinicians to
      adapt their treatment protocols to cater for the individual needs of their
      patients.

PMID- 20152303
TI  - Direct and indirect effects of the temperament and character on alexithymia: a
      pathway analysis with mood and anxiety.
AB  - OBJECTIVE: We aimed to assess the pathway from personality to alexithymia through
      mood and anxiety as mediators. METHOD: Three hundred thirty-four subjects (130
      male), whose psychiatric health was verified by Structured Clinical Interview for
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I
      disorders, completed the Toronto Alexithymia Scale-20 (TAS-20), the Temperament
      and Character Inventory, the State-Trait Anxiety Inventory (STAI), and the Center
      for Epidemiological Studies-Depression scale (CES-D). The schematic models for
      the pathway analysis from Temperament and Character Inventory (TCI) to TAS-20
      scores were made. RESULTS: Low reward dependence (RD), low self-directedness (S
      D), and high cooperativeness (CO) had paths to TAS-20 total (P = .000, P = .000,
      and P = .042, respectively). S-D had also an indirect path via STAI-state to TAS
      total. On TAS-20 factor 1, low RD, low S-D, and high self-transcendence (ST) had
      direct effects (P = .004, P = .000, and P = .000, respectively). S-D had also an
      indirect path via STAI-state and (CES-D) on TAS-20 factor 1. On TAS factor 2, low
      novelty seeking (NS), high harm avoidance (HA), low RD, low S-D, and high
      cooperativeness (CO) had direct effects (P = .005, P = .011, P = .000, P = .000,
      and P = .004, respectively). On TAS-20 factor 3, low RD and S-D had direct
      effects (P = .002 and P = .000, respectively). CONCLUSION: Current results
      suggest that although alexithymia is affected by the personality, state-dependent
      mood and anxiety may mediate the relationship between alexithymia and
      personality.

PMID- 20152304
TI  - Normative data for the Tygerberg Cognitive Battery and Mini-Mental Status
      Examination in a South African population.
AB  - BACKGROUND: Normative data for the Tygerberg Cognitive Battery (TCB) and Mini
      Mental Status Examination (MMSE) (in South Africa) have not been formally
      examined before. The TCB was developed for the bedside pen-and-paper screening of
      cognitive impairment in each of the 6 main cognitive domains, including attention
      and concentration, speech, memory, praxis, gnosis, and executive functioning. The
      test is also used to diagnose different neuropsychiatric conditions. The MMSE is
      an established screen of cognitive status, which is often used as a comparative
      standard for novel screening tests such as the TCB. The TCB was initially
      developed in English and Afrikaans, and a Xhosa version was also initiated with
      this study so that the 3 most common languages of the region could be
      accommodated. AIMS: The first aim of the study was to estimate normative test
      performance on the TCB and MMSE among controls, and the second aim was to develop
      a Xhosa version of the TCB. METHODS: Assessments of the TCB and MMSE were carried
      out in a population of healthy individuals (n = 157). In addition, healthy Xhosa
      speaking participants (n = 14) were screened using a Xhosa version of the TCB.
      RESULTS: Reliability scores for all forms of the TCB were satisfactory. Age and
      education correlated significantly with TCB scores (r = -0.26, P < .01; r = 0.64,
      P < .01, respectively), whereas only education significantly correlated with MMSE
      scores (r = 0.32, P < .05). Normative values were calculated accordingly, that
      is, controlled for the effects of age and education. The TCB scores also
      correlated significantly with MMSE scores (r = 0.49, P < .05), demonstrating the
      potential of the TCB to serve as an alternate cognitive assessment tool, along
      with the MMSE, to focus neuropsychiatric investigations. Scores on the Xhosa
      version differed significantly on speech, praxis, and gnosis between the
      Afrikaans and English participant scores. CONCLUSION: These normative data can be
      used to increase precision and to provide an impartial evaluation when applying
      TCB to evaluate the cognitive ability of neuropsychiatrically impaired adult
      patients. However, age and education effects should be considered when computing
      the results of cognitive assessment.

PMID- 20152306
TI  - Optical coherence tomography in Barrett's esophagus: the road to clinical
      utility.

PMID- 20152307
TI  - What the heck is this new periductal hypoechoic sign?

PMID- 20152308
TI  - Needle-knife sphincterotomy and post-ERCP pancreatitis: time to lower the
      threshold for the needle?

PMID- 20152309
TI  - Indications and detection, completion, and retention rates of small-bowel capsule
      endoscopy: a systematic review.
AB  - BACKGROUND: Capsule endoscopy (CE) has been widely used in clinical practice.
      OBJECTIVE: To provide systematically pooled results on the indications and
      detection, completion, and retention rates of small-bowel CE. DESIGN: A
      systematic review. MAIN OUTCOME MEASUREMENTS: We searched the PubMed database
      (2000-2008) for original articles relevant to small-bowel CE for the evaluation
      of patients with small-bowel signs and symptoms. Data on the total number of
      capsule procedures, the distribution of different indications for the procedures,
      the percentages of procedures with positive detection (detection rate), complete
      examination (completion rate), or capsule retention (retention rate) were
      extracted and/or calculated, respectively. In addition, the detection,
      completion, and retention rates were also extracted and/or calculated in relation
      to indications such as obscure GI bleeding (OGIB), definite or suspected Crohn's
      disease (CD), and neoplastic lesions. RESULTS: A total of 227 English-language
      original articles involving 22,840 procedures were included. OGIB was the most
      common indication (66.0%), followed by the indication of only clinical symptoms
      reported (10.6%), and definite or suspected CD (10.4%). The pooled detection
      rates were 59.4%; 60.5%, 55.3%, and 55.9%, respectively, for overall, OGIB, CD,
      and neoplastic lesions. Angiodysplasia was the most common reason (50.0%) for
      OGIB. The pooled completion rate was 83.5%, with the rates being 83.6%, 85.4%,
      and 84.2%, respectively, for the 3 indications. The pooled retention rates were
      1.4%, 1.2%, 2.6%, and 2.1%, respectively, for overall and the 3 indications.
      LIMITATIONS: Inclusion and exclusion criteria were loosely defined. CONCLUSIONS:
      The pooled detection, completion, and retention rates are acceptable for total
      procedures. OGIB is the most common indication for small-bowel CE, with a high
      detection rate and low retention rate. In addition, angiodysplasia is the most
      common finding in patients with OGIB. A relatively high retention rate is
      associated with definite or suspected CD and neoplasms.

PMID- 20152310
TI  - Balloon by balloon, inch by inch.

PMID- 20152311
TI  - Computers for colonoscopy training: where do they fit in?

PMID- 20152312
TI  - North of 100 and south of 500: where does the "sweet spot" of colonoscopic
      competence lie?

PMID- 20152313
TI  - The best screening test for colorectal cancer is the one that gets done well.

PMID- 20152314
TI  - Somewhere over the rainbow.

PMID- 20152315
TI  - Endoluminal management of anastomotic dehiscence after esophagectomy: an
      increasing quiver of options reflects the difficulty in realizing a definitive
      therapy.

PMID- 20152316
TI  - Eosinophilic esophagitis misdiagnosed twice as esophageal candidiasis.

PMID- 20152317
TI  - Endoscopic management of multiple colonic fistulae secondary to acute
      pancreatitis (with video).

PMID- 20152318
TI  - Percutaneous transesophageal gastrostomy tube placement: an alternative to
      percutaneous endoscopic gastrostomy in patients with intra-abdominal metastasis.
AB  - BACKGROUND: PEG/jejunostomy (PEG/J) is often placed in patients with metastatic
      gastric cancer for palliating bowel obstruction or for feeding. However, PEG/J
      placement may not always be possible for many reasons. OBJECTIVE: We wish to
      bring attention to the percutaneous transesophageal gastrostomy/jejunostomy
      (PTEG/J) as a viable alternative to nasogastric decompression in patients who are
      not candidates for PEG/J. PTEG/J is a largely unknown technique in the United
      States that designed to gain access to the stomach and proximal small bowel in
      these patients. We describe the use of PTEG/J in 3 patients with metastatic
      gastric cancer by using resources and techniques readily available in a well
      stocked interventional radiology suite. PATIENTS: In the first case, percutaneous
      transesophageal gastrostomy (PTEG) was placed for palliation of intractable
      nausea and vomiting in a 37-year-woman with diffuse gastric cancer and peritoneal
      carcinomatosis. In the second case, PTEG was extended into the jejunum for
      feeding a 60-year-old woman with metastatic gastric cancer. In the third case,
      PTEG extending into the jejunum was placed in a 69-year-old man for palliation of
      bowel obstruction caused by metastatic gastric cancer and peritoneal
      carcinomatosis. METHODS: After adequate sedation is administered, a 22 x 4-mm
      balloon catheter is passed into the esophagus over a guidewire just below the
      thoracic inlet. The balloon is ruptured with a needle passed through the neck
      under US guidance. A guidewire is then passed through the needle into the balloon
      and carried into the stomach or proximal small bowel by advancing the balloon
      catheter. The track is then dilated over the guidewire and a pigtail 45-cm-long
      14F nephrostomy tube then passed into the stomach or into the proximal small
      bowel over the guidewire. The catheter is secured by suturing to the skin of the
      neck. RESULTS: PTEG/J was effective in achieving palliation or feeding in our
      patients. No complications occurred. CONCLUSIONS: PTEG/J is a safe and effective
      alternative to standard percutaneous gastrostomy/jejunostomy tube placement for
      decompression of bowel obstruction or feeding in appropriately selected patients.

PMID- 20152319
TI  - EUS-guided hepaticogastrostomy with a fully covered metal stent as the biliary
      diversion technique for an occluded biliary metal stent after a failed ERCP (with
      videos).
AB  - BACKGROUND: Percutaneous transhepatic biliary drainage (PTBD) may be the last
      resort for an occluded biliary metal stent when the ERCP was unsuccessful.
      OBJECTIVE: Because an EUS-guided biliary drainage has been proposed as an
      effective alternative for PTBD after a failed ERCP, we conducted this study to
      determine the feasibility and usefulness of an EUS-guided hepaticogastrostomy
      (EUS-HG) with a fully covered self-expandable metal stent (FCSEMS) for an
      occluded biliary metal stent after a failed ERCP. DESIGN: A case study. SETTING:
      A tertiary referral center. PATIENTS AND INTERVENTIONS: Five patients who had an
      occluded biliary metal stent inserted after a hilar bilateral metal stent or a
      combined duodenal and biliary metal stent insertion and for whom reinterventional
      ERCP was unsuccessful underwent an EUS-HG with an FCSEMS for alternative PTBD.
      MAIN OUTCOME MEASUREMENTS: Technical and functional success, procedural
      complications, reinterventional rate after EUS-HG with an FCSEMS, and short-term
      stent patency. RESULTS: In all 5 patients, an EUS-HG with an FCSEMS was
      technically successful. No procedural complications, such as bile peritonitis,
      cholangitis, and pneumoperitoneum, were observed. Functional success was also
      100% (5/5). During the follow-up period (median 152 days, range 64-184 days), no
      late complications, such as stent migration and occlusion, were observed. Thus,
      no biliary reintervention was performed during the follow-up period. LIMITATIONS:
      A small series of patients without a control group. CONCLUSIONS: The EUS-HG with
      an FCSEMS may be feasible, effective, and an alternative PTBD for an occluded
      biliary metal stent after a failed ERCP.

PMID- 20152320
TI  - Previous experience and long-term follow-up of Schatzki's rings treated with
      electrosurgical incision.

PMID- 20152321
TI  - The mucosal pattern in the non-neoplastic gastric mucosa by using magnifying
      narrow-band imaging endoscopy significantly correlates with gastric cancer risk.

PMID- 20152322
TI  - Occult adenocarcinoma after esophagectomy for Barrett's high-grade dysplasia.

PMID- 20152323
TI  - EUS-guided celiac plexus block for chronic pancreatitis: a placebo-controlled
      trial should be the first priority.

PMID- 20152326
TI  - Prospective randomized trial comparing EUS and EGD for transmural drainage of
      pancreatic pseudocysts: a need for a large randomized study.

PMID- 20152327
TI  - Improve anorectal examination by the cap-assisted colonoscopy method.

PMID- 20152331
TI  - Colon agenesis with ileovesical fistula and anorectal malformation.
AB  - Colonic agenesis is a rare cause of congenital bowel obstruction and is usually
      associated with other malformations such as abdominal wall defects or
      gastrointestinal, cardiac, urogenital, and musculoskeletal lesions. Although many
      uncommon types have been reported, ileovesical fistula (IVF) associated with
      total colonic agenesis (TCA) has not been reported in a newborn with anorectal
      malformation (ARM). This is the first report of a 1-day-old newborn with ARM,
      IVF, and TCA.

PMID- 20152332
TI  - Pediatric alveolar echinococcosis invading the diaphragm and spreading to the
      chest and abdominal wall.
AB  - Hepatic alveolar echinococcosis (AE) is an endemic disease in certain parts of
      the world and relatively rare in children. This report describes a 9-year-old
      girl with hepatic AE invading the diaphragm and directly spreading to the chest
      and abdominal wall. She was treated by surgical extirpation and albendazole
      therapy. In advanced hepatic AE, combined therapy of surgical and medical
      intervention is thought to improve the prognosis.

PMID- 20152333
TI  - Malignant phyllodes tumor in an 11-year-old premenarchal girl.
AB  - Phyllodes tumor is uncommon in children, and the malignant form is rare. There
      have only been a few cases of benign phyllodes tumor reported in peripubertal
      children and only one malignant case. We report the second case of malignant
      phyllodes tumor in a premenarchal 11-year-old girl.

PMID- 20152334
TI  - Three small testes in left hemiscrotum: a rarer case of polyorchidism.
AB  - Polyorchidism is a rare congenital anomaly. A review of literature has yielded
      about 100 cases. We describe a rarer case of polyorchidism consisting of 3 testes
      on left hemiscrotum and one normal testis in right hemiscrotum. Diagnosis and
      management are discussed.

PMID- 20152335
TI  - Congenital cystic adenomatoid malformation of lung type 1.
AB  - Congenital cystic adenomatoid malformation, a rare developmental, hamartomatous
      abnormality of the lung, usually is unilateral, is localized, and presents in
      early infancy. Delayed occurrence in older children and multilobar involvement
      are rare. We describe a case of congenital cystic adenomatoid malformation type 1
      with multilobar involvement, associated emphysema, and coexistent
      tracheobronchopathia osteochondroplastica in an adolescent girl for whom the
      correct diagnosis was achieved only on histologic examination. The importance of
      an accurate diagnosis of this entity enables proper subtyping, management to
      minimize the risk of infections and malignancy, and exclusion of associated
      malformations.

PMID- 20152336
TI  - Multiple synchronous tumors in a child with Fanconi anemia.
AB  - Fanconi anemia (FA) is an autosomal recessive inherited syndrome characterized by
      congenital abnormalities, aplastic anemia, and a high likelihood of developing
      cancer. We describe a child who presented with 2 synchronous solid tumors (Wilms
      tumor and neuroblastoma), later found to have FA, who developed severe toxicity
      and died after a first cycle of chemotherapy. Our experience emphasizes that a
      predisposing genetic condition should be sought in cases of multiple tumors and
      that managing FA patients with cancer can be particularly difficult.

PMID- 20152337
TI  - Delayed presentation of hypertrophic pyloric stenosis: a rare case.
AB  - Hypertrophic pyloric stenosis (HPS) is the most common cause of gastric outlet
      obstruction in infants, with an incidence of 1.5 to 3 per 1000 live births, and
      classically presents at 3 to 4 weeks of age. Delayed presentation of HPS is an
      extremely rare occurrence after early infancy. With the exclusion of congenital
      HPS, gastric outlet obstruction in childhood is a rare condition (1:100,000). We
      report a case of delayed presentation of HPS in a 4 1/2-year-old child in whom
      the pylorus was hypertrophied and appeared like an "olive," and for which
      pyloromyotomy was curative.

PMID- 20152338
TI  - Tissue engineering and regenerative medicine: from first principles to state of
      the art.
AB  - This lecture updates pediatric surgeons on the state of the science of tissue
      engineering and regenerative medicine.

PMID- 20152339
TI  - Endosurgery of the future, today: lessons on how to be an innovator.
AB  - This lecture summarizes the elements of innovation and demonstrates how one can
      apply the principles every day to be an effective surgical innovator.

PMID- 20152340
TI  - Comparison of childhood appendicitis management in the regional paediatric
      surgery unit and the district general hospital.
AB  - BACKGROUND/PURPOSE: Ongoing debate surrounds the future provision of general
      paediatric surgery. The aim of this study was to compare outcomes for childhood
      appendicitis managed in a district general hospital (DGH) and a regional
      paediatric surgical unit (RU). METHODS: Data collected retrospectively for a 2
      year period in a DGH were compared with data collected prospectively for 1 year
      in an RU, where appendicitis management is guided by a care pathway. Children
      aged 6 to 15 years were included. RESULTS: Four hundred and two patients were
      included (DGH ,196; RU, 206). There were more cases of gangrenous/perforated
      appendicitis in the RU (P < .0001). In the DGH, fewer patients received
      preoperative antibiotics (P < .0001) or underwent preoperative pain scoring (P <
      .0001). When adjusted for case mix, the relative risk of complications for a
      child managed at the DGH was 1.76 (95% confidence interval, 1.44-2.16; P < .0001)
      and that of readmission was 1.76 (95% confidence interval, 1.43-2.16; P < .0001)
      when compared with the RU. CONCLUSIONS: Patients with appendicitis managed in the
      DGH had a higher risk of complications and readmission. However, this appears to
      be related to the use of a care pathway at the RU. Introduction of a care pathway
      in the DGH may improve outcomes and thus support the ongoing provision of general
      paediatric surgery.

PMID- 20152341
TI  - Fragmented international volunteerism: need for a global pediatric surgery
      network.
AB  - INTRODUCTION: Pediatric general surgeons volunteering internationally often work
      independently, some without prior assessment of the needs of those they wish to
      assist. Consequently, care may be inefficient, duplicated, or misdirected. A
      study was performed to assess whether a network for pediatric surgery volunteer
      work exists. METHODS: A search of the Internet was performed to determine whether
      a pediatric surgery network exists. Worldwide pediatric surgery societies were
      identified and grouped by country according to income. Web sites for medical
      volunteer organizations were examined for links to a network of pediatric surgery
      volunteer work. RESULTS: A search of the Internet revealed no pediatric surgery
      volunteer network. Ninety-seven pediatric surgery societies were identified.
      Fifty-one of the organizations were identified as residing in low- and middle
      income countries. Searching 50 Web sites for these societies revealed no existing
      pediatric surgery network. Of 45 Web sites for volunteer medical work, 1 surgery
      networking Web site was identified. Only 4 pediatric general surgery
      international volunteer opportunities were cited on that Web site. CONCLUSIONS:
      This study demonstrated that no pediatric surgery volunteer network exists. By
      identifying pediatric surgery organizations in low- and middle-income countries,
      it is speculated that one might link the surgeons in these regions with those
      wishing to volunteer their services.

PMID- 20152342
TI  - Timing of surgical intervention in necrotizing enterocolitis can be determined by
      trajectory of metabolic derangement.
AB  - PURPOSE: Seven metrics of metabolic derangement were evaluated as contributors to
      clinical decision support for operative intervention in infants with suspected
      necrotizing enterocolitis (NEC). METHODS: Records of infants with suspected NEC
      without radiologic evidence of free air were queried for presence of 7 components
      of metabolic derangement (CMD), consisting of positive blood culture, acidosis,
      bandemia, thrombocytopenia, hyponatremia, hypotension, or neutropenia. Cases were
      stratified by clinical decision after each surgical evaluation as observation
      (OBS) or intervention (INT). Good outcome was defined as full enteric feeding by
      discharge and bad outcome as death or ongoing parenteral alimentation. Eleven
      infants undergoing operative intervention after an initial decision to observe
      were evaluated as matched pairs. Components of metabolic derangement/case and
      frequency of each CMD were determined for OBS and INT. Mann-Whitney U test was
      used to compare proportions of CMD in each group. Outcome was compared using
      chi(2). Observation was then stratified by outcome to determine whether 3 or more
      metabolic derangements warranting operative intervention would have changed
      initial clinical decision. The 11 matched cases were similarly analyzed using
      Wilcoxon-matched pairs. RESULTS: Between March 2005 and July 2008, 35 infants
      with NEC received 53 surgical evaluations. A median of 1 CMD/case was defined in
      32 instances of OBS. Surgical intervention was carried out in 19 infants with a
      median of 3 CMD/case. Mann-Whitney U test indicated significant difference in the
      frequencies of each CMD component in OBS vs INT (P = .04). Good outcome was
      achieved in 75% of OBS and 63% of INT (non-significant, NS). Analysis of OBS by
      outcome demonstrated a median 1 CMD/case of 25 with good outcome and 3 CMD/case
      in infants with bad outcome. Frequency of CMD was significantly higher in infants
      with bad outcome (P = .02). Wilcoxon-matched pair analysis of the 11 infants with
      paired evaluations demonstrated a similar distribution and frequency of CMD.
      CONCLUSION: Progressive metabolic derangement of infants with NEC can be
      clinically tracked. The appearance of any 3 of these 7 metrics indicates timely
      operative intervention. Application of CMD trajectory to timing of surgical
      intervention may improve outcome and define the relationship between specific CMD
      and operative risk.

PMID- 20152343
TI  - Effect of maternal human immunodeficiency virus status on the outcome of neonates
      with necrotizing enterocolitis.
AB  - AIM: The aim of the study was to assess the impact of human immunodeficiency
      virus (HIV) exposure on survival and extent of disease in necrotizing
      enterocolitis (NEC). PATIENTS AND METHODS: All patients with NEC requiring
      surgery between June 1998 and June 2008 were analyzed. Three groups were
      identified: those born to HIV-positive (HIV+) mothers, those born to HIV-negative
      (HIV-) mothers, and those with an unknown HIV status. Primary outcome measure was
      survival to discharge. Secondary outcome measure was extent of disease. RESULTS:
      One hundred nine infants (mean gestational age, 31 weeks; birth weight, 1413 g)
      underwent surgery for NEC. Gestational age, birth weight, and day of presentation
      were similar in all 3 groups, showing no statistical difference. The HIV+ group
      consisted of 22 infants, of which 13 (59%) died and 2 (9%) had panintestinal
      necrosis. The HIV- group consisted of 48 infants, of which 11 (23%) died, with
      3(6%) having panintestinal necrosis. The remaining group of HIV (unknown)
      consisted of 38 infants, of which 14 (37%) died, with 2 (5%) having panintestinal
      necrosis. The latter group was not included in the analysis; but comparing the
      HIV+ and HIV- groups, there was a statistically higher chance of death (odds
      ratio = 4.8, P = .05). There was no difference statistically in the extent of
      disease. CONCLUSION: Neonates with NEC born to HIV+ mothers have a higher
      mortality.

PMID- 20152344
TI  - Morbidity after surgical treatment of isolated intestinal perforation and
      necrotizing enterocolitis is similar in preterm infants weighing less than 1500
      g.
AB  - INTRODUCTION: Isolated intestinal perforation (IIP) and necrotizing enterocolitis
      (NEC) seem to be separate diseases, though their surgical treatment is similar.
      We compared the morbidity after surgery for IIP and NEC in preterm infants (birth
      weight <1500 g). PATIENTS AND METHODS: Isolated intestinal perforation was
      defined as intestinal perforation with associated necrosis less than 5% of bowel
      length and NEC as necrosis of 5% or more of bowel length +/- perforation. Outcome
      measures included time to full enteral feeds, incidence of total parenteral
      nutrition-associated cholestasis, and nutritional and neurologic status up to 60
      months of age. Data are quoted as median (range). MAIN RESULTS: Sixty-one
      surviving patients treated between 1986 and 2006 were retrospectively reviewed
      (IIP: n = 32 versus NEC: n = 29). Median % resection of small and large bowel in
      IIP and NEC was 2% (1%-22%) versus 12% (6%-32%), and 5% (2%-13%) versus 7% (2%
      25%), respectively (P < .05 in both). There was no significant difference in
      gestational age, birth weight, incidence of cerebral hemorrhage, respiratory
      distress syndrome, or surgical technique (enterostomy or primary anastomosis).
      Median time to enteral feeds, incidence of total parenteral nutrition-associated
      cholestasis, length of ventilation, and ultimate nutritional and neurologic
      outcome did not differ statistically significantly between the groups.
      CONCLUSION: Surgery in NEC resulted in more extensive intestinal resection than
      in IIP. However, subsequent morbidity was similar in both groups.

PMID- 20152346
TI  - Graft-vs-host disease after small bowel transplantation in children.
AB  - PURPOSE: Graft-vs-host disease (GVHD) is a rare complication of transplantation
      of organs rich in immunocompetent cells. The goal of this study was to report the
      features of GVHD after small bowel transplantation (SBTx) in children. METHODS:
      The study involved a retrospective review of patients undergoing SBTx between
      1999 and 2009 who had GVHD. RESULTS: Of 46 children receiving 52 intestinal
      grafts (2 liver-intestine and 3 multivisceral), 5 (10%) developed GVHD. Median
      age at transplant was 42 (19-204) months. Baseline immunosupression consisted of
      tacrolimus and steroids supplemented with thymoglobulin (n = 2) or basiliximab (n
      = 3) for induction. Median time between transplantation and GVHD was 47 (16-333)
      days. All patients had generalized rash, 2 had diarrhea, and 2 had respiratory
      symptoms. Other symptoms were glomerulonephritis (n = 1) and conjunctivitis (n =
      1). Four developed severe hematologic disorders. The diagnosis was confirmed by
      skin biopsy in 4 patients and supported by chimerism studies in two. Colonoscopy
      and opthalmoscopic findings were also suggestive in one. Treatment consisted of
      steroids and decrease of tacrolimus, with partial response in four. Other
      immunosuppressants were used in refractory or recurrent cases. Three patients
      died within 4 months after diagnosis. CONCLUSION: Graft-vs-host disease is a
      devastating complication of SBTx, with high mortality probably associated with
      severe immunologic dysregulation.

PMID- 20152345
TI  - Peritoneal drainage does not stabilize extremely low birth weight infants with
      perforated bowel: data from the NET Trial.
AB  - INTRODUCTION: Proponents of peritoneal drainage (PD) hypothesize that it allows
      stabilization before laparotomy. We examined this hypothesis by comparing
      clinical status before and after either PD or primary laparotomy (LAP). METHODS:
      In an ethically approved, international, prospective randomized controlled trial
      (2002-2006), extremely low birth weight (<1000 g) infants with pneumoperitoneum
      received primary PD (n = 35) or LAP (n = 34). Physiologic data were collected
      prospectively and organ failure scores calculated and compared between
      preprocedure and day 1 after procedure. Data, expressed as mean +/- SD or median
      (range), were analyzed using appropriate statistical tests. RESULTS: There was no
      postprocedure improvement in either PD or LAP group comparing heart rate (PD, P =
      1.0; LAP, P = .6), blood pressure (PD, P = .6; LAP, P = .8), inotrope requirement
      (PD, P = .2; LAP, P = .3), or Arterial partial pressure of oxygen/fraction of
      inspired oxygen ratio (PD, P = .1; LAP, P = .5). Infants managed with PD had a
      worsening cardiovascular status (P = .05). There were no differences in total
      organ failure score in either group (PD, P = .5; LAP, P = 1). Only 4 infants
      survived with PD alone with no difference between preprocedure and postprocedure
      organ failure score (P = .4). CONCLUSIONS: Peritoneal drainage does not
      immediately improve clinical status in extremely low birth weight infants with
      bowel perforation. The use of PD as a stabilizing or temporizing measure is not
      supported by these results.

PMID- 20152347
TI  - The diagnosis and management of recurrent tracheoesophageal fistulas.
AB  - PURPOSE: This review provides a blueprint to deal with the diagnosis and
      management of recurrent tracheoesophageal fistulas. METHODS: A retrospective
      review over 27 years found 26 recurrent tracheoesophageal fistulas. Descriptive
      statistical analyses were performed. RESULTS: In this cohort of 26 patients, 18
      had a leak after their primary operation; and 22 had respiratory symptoms leading
      to the discovery of the recurrent fistula. The diagnosis was made by contrast
      study in 24. The repairs entailed placing a catheter through the fistula;
      separating the trachea and esophagus using sharp dissection; and placing tissue,
      preferably pericardium, between the suture lines. Postoperative complications
      included 7 anastamotic leaks, 4 strictures, and 3 recurrent fistulas. Long-term
      follow-up (median of 84 months) showed that 21 took all of their nutrition by
      mouth, 3 were tube fed, and 2 required a combination. Of the 23 patients with
      growth chart data, 16 fell in the first quartile of the growth chart, whereas
      none fell between the 75th and 100th percentile. CONCLUSION: This series, the
      largest to date, describes characteristics of recurrent tracheoesophageal
      fistulas, including techniques to make the diagnosis and provide a secure closure
      of the fistula, and the long-term outcomes of these patients.

PMID- 20152348
TI  - Colonic interposition for esophageal replacement in children remains a good
      choice: 33-year median follow-up of 65 patients.
AB  - INTRODUCTION: Gastric pull-up has become the predominant technique for esophageal
      replacement because of allegedly deficient results of colon grafts. This
      retrospective study examines the long-term results in a large series of colonic
      interpositions. PATIENTS AND METHOD: One hundred six children (median, 2.9 years;
      range, 0.32-15 years) had their esophagus replaced between 1965 and 2008, of
      which 96 had colon grafts. Those survivors who were 18 years and older were
      contacted and, if willing, interviewed, examined, and had their functional
      ability rated using the Karnofsky index. RESULTS: Ninety-six children had
      undergone a colon graft, and of these, 9 (9.3%) died. There were 65 long-term
      survivors whose indications for surgery included caustic injury (n = 32), failed
      tracheoesophageal fistula repair (n = 16), pure esophageal atresia (n = 14), and
      others (n = 3). The graft was either retrosternal (n = 49) or mediastinal (n = 16
      patients). Twelve patients were unavailable for long-term assessment. After a
      median follow-up of 33.3 (11-41) years, 23 (43%) of 53 individuals experienced
      mild symptoms of reflux; scoliosis, 12 (22%) of 53, and/or other complications,
      15 (27%) of 53 required further surgery. Thirty-two patients (60%) with Karnofsky
      indexes of 80% or higher felt healthy, 19 (36%) had mild life-style limitations
      (index, 40%-80%), and 2 had indexes less than 40%. Most patients live normal
      lives. CONCLUSIONS: Colon conduits restored gastrointestinal continuity with
      limited mortality and considerable morbidity but good functional outcome and
      health perception in the long-term. Our study suggests that colon grafts are no
      worse than gastric pull-ups in the long-term.

PMID- 20152349
TI  - A comparison of laparoscopic and open Nissen fundoplication and gastrostomy
      placement in the neonatal intensive care unit population.
AB  - INTRODUCTION: The aim of this study was to compare outcomes after laparoscopic
      and open techniques for Nissen fundoplication and gastrostomy placement in the
      neonatal intensive care unit (NICU) population. METHODS: The medical records for
      NICU inpatients who underwent laparoscopic and open Nissen fundoplication and
      gastrostomy placement from August 2002 to August 2008 were reviewed after
      Institutional Review Board approval. Each technique was compared with regard to
      operative time, estimated blood loss, postoperative 24-hour narcotic
      requirements, time to goal feeds, and complication rates. Analysis of variance
      was used to determine statistical significance. Data are quoted as mean +/- SEM.
      RESULTS: Fifty-seven NICU patients underwent fundoplication and gastrostomy
      placement (25 laparoscopic and 32 open). The time to goal feeds was significantly
      shorter for the laparoscopic group (4.3 +/- 0.4 vs 6.1 +/- 0.6 days, P = .04).
      The 24-hour postoperative narcotic requirement was significantly lower in the
      laparoscopic group (0.24 +/- 0.05 vs 0.55 +/- 0.08 mg/kg, P = .007). Operation
      times (111 +/- 5 [open] vs 113 +/- 5 minutes, P = .76) and estimated blood loss
      (13 +/- 2 [open] vs 11 +/- 1 mL, P = .33) were comparable for both groups.
      CONCLUSION: Laparoscopic and open techniques for Nissen fundoplication with
      gastrostomy placement are safe and appropriate treatment methods with equivalent
      operating times for the treatment of gastroesophageal reflux in the NICU
      population.

PMID- 20152350
TI  - Gastric emptying scans: unnecessary preoperative testing for fundoplications?
AB  - PURPOSE: Delayed gastric emptying (DGE) as indicated by preoperative gastric
      emptying scan (GES) is one rationale for performing a gastric emptying procedure
      (GEP) at time of fundoplication for gastroesophageal reflux disease (GERD).
      However, the role of GES and GEP in the surgical management of GERD remains
      unclear. We examined the use of preoperative GES in fundoplication patients.
      METHODS: Retrospective chart review of patients undergoing fundoplication from
      2000 to 2005 in a single institution including patient demographics, operative
      procedure, and postoperative outcomes at 1-year follow-up was analyzed using
      chi(2) test. RESULTS: Of 76 fundoplication patients, 39 (51%) had preoperative
      GES with 11 patients (28%) having DGE and 16 GEP performed. Developmentally
      delayed children were more likely to have GES. There were no significant
      differences in postoperative complications, length of hospital stay, or use of
      anti-GERD medications at 1 year between patients who had preoperative GES and
      those who did not. In the developmentally delayed group, there were no
      differences in outcomes between those with preoperative GES and those who did
      not. CONCLUSIONS: There were no differences in outcomes for GERD patients with or
      without preoperative GES or GEP postfundoplication. The use of GES in the
      management of GERD requires further evaluation.

PMID- 20152351
TI  - Thoracoscopic repair of congenital diaphragmatic hernia: intraoperative
      ventilation and recurrence.
AB  - INTRODUCTION: Thoracoscopic repair of congenital diaphragmatic hernia (CDH) has
      been described, but its efficacy and safety have not been validated. The aim was
      to compare our experience of thoracoscopy with laparotomy repair. METHODS: After
      ethics approval, we reviewed the notes of neonates with CDH operated in our
      institution between 2003 and 2008. Two historical groups were compared: infants
      who underwent laparotomy (2003-2008) or thoracoscopy (2007-2008). Data were
      compared by t test or Mann-Whitney tests. RESULTS: Thirty-five children had open
      repair of CDH, and 13 had thoracoscopic repair. Groups were homogeneous for age
      and weight. Five (38%) neonates who had thoracoscopy were converted to open for
      surgical difficulties (n = 4) and O(2) desaturation (n = 1). Patch repair was
      used in 12 (34%) open and 6 (46%) thoracoscopic repairs. End-tidal CO(2) was
      significantly elevated during thoracoscopy, but this was not reflected in
      arterial CO(2) or pH. There were 3 (8%) recurrences after open repair and 2 (25%)
      after thoracoscopy (P = .19). CONCLUSION: Thoracoscopic repair of CDH is
      feasible. Arterial blood gases should be closely monitored. Despite higher
      EtCO(2), conversion to open was mainly because of difficult repair. A randomized
      trial is necessary to assess the effect of thoracoscopy on ventilation and
      recurrences.

PMID- 20152352
TI  - Bronchopulmonary innervation defects in infants and rats with congenital
      diaphragmatic hernia.
AB  - INTRODUCTION: Pulmonary morbidity in survivors of congenital diaphragmatic hernia
      (CDH) is caused by hypoplasia, barotraumas, or other reasons. We have previously
      shown deficient tracheal innervation in rats with CDH. Now we examine whether
      bronchopulmonary innervation is also abnormal in both infants and rats with CDH.
      MATERIAL AND METHODS: Sections of E15, E18, and E21 rat lungs were immunostained
      for Protein gene product 9.5 and S100 antibodies. Similar immunostaining was
      performed on tissue from infants dying from CDH (n = 6) and other causes (n = 6)
      with Neurofilament, S100, and Rearranged during transfection antibodies. Nerve
      trunks/bronchus were counted, and the proportion of glial and RET-positive
      cells/bronchial surface was calculated. Glial cell-line derived neurotrophic
      factor protein and mRNA were measured in rat lungs. RESULTS: Nerve
      trunks/bronchus were decreased in infants and rat fetuses with CDH. In contrast,
      glial and RET-positive cells/bronchial surface were increased in infants and rats
      with CDH. Both lungs were equally affected. GDNF protein was high, whereas GDNF
      mRNA was decreased in preterm animals with CDH. CONCLUSIONS: The lungs of infants
      and rats with CDH have decreased neural components compensated by increased
      supporting glial cells and persistence high expression of RET and GDNF protein.
      Because bronchopulmonary innervation controls airway smooth muscle, vessels, and
      glandular secretions, it is tempting to hypothesize that these deficiencies might
      play a role in respiratory morbidity in CDH.

PMID- 20152353
TI  - Spatiotemporal alteration in phosphatidylinositide 3-kinase-serine/threonine
      protein kinase B signaling in the nitrofen-induced hypoplastic lung.
AB  - PURPOSE: The pathogenesis of pulmonary hypoplasia in congenital diaphragmatic
      hernia (CDH) is not fully understood. The serine/threonine protein kinase B (AKT)
      plays important roles for lung morphogenesis through epithelial-mesenchymal
      interaction in phosphatidylinositide 3-kinase (PI3K)-dependent manner. It has
      been reported that the lung explant morphogenesis in mice is interfered by
      inhibitors of the PI3K-AKT pathway. We hypothesized that PI3K and AKT gene and
      protein expression/distribution are altered during epithelial morphogenesis in
      the nitrofen-induced hypoplastic lung. METHODS: Pregnant rats were exposed to
      either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were
      harvested on D15, D18, and D21 and divided into 3 groups as follows: control,
      nitrofen with CDH (CDH[-]), and nitrofen without CDH (CDH[+]) (n = 8 at each time
      point, respectively). Reverse transcription polymerase chain reaction and
      immunohistochemistry were performed. RESULTS: Messenger RNA expression levels of
      PI3K at D21 was significantly decreased in CDH(-) and CDH(+) group (5.71 +/- 0.85
      and 6.80 +/- 0.88, respectively) compared to controls (8.95 +/- 3.22; P < .05).
      Messenger RNA levels of AKT were also significantly decreased at D18 in CDH(-)
      and CDH(+) lungs (1.21 +/- 0.16 and 1.20 +/- 0.32, respectively) compared to
      controls (1.62 +/- 0.14; P < .01). The PI3K immunoreactivity was diminished in
      the distal epithelium at D18 and decreased in the overall intensity at D21 in
      hypoplastic lungs compared to controls. The AKT immunoreactivity was decreased in
      mesenchyme at D18 and decreased overall intensity at D21 in CDH lungs compared to
      controls. CONCLUSION: Spatiotemporal alteration of pulmonary PI3K and AKT gene
      and protein expression during epithelial morphogenesis may interfere with
      epithelial-mesenchymal interaction, causing pulmonary hypoplasia in CDH by
      disrupting PI3K-AKT signaling pathway.

PMID- 20152354
TI  - Conservative management of isolated splenic abscess in children.
AB  - INTRODUCTION: Isolated splenic abscesses (SAs) are rare in children. We report a
      single-center experience with emphasis on their diagnosis, etiology, treatment,
      and outcome. METHODS: This is a retrospective review. RESULTS: Eighteen children
      (age, 3-16 years; male-female ratio, 5:1) were managed over a period of 8 years
      in a tertiary-care institution. Presenting symptoms included fever, abdominal
      pain, and anorexia. Splenomegaly was present in 12 (67%), leukocytosis in 9
      (50%), and thrombocytosis in 12 (67%) patients. Associated diseases were
      thalassemia (1), tuberculosis (1), and typhoid fever (9). Solitary and multiple
      SAs were seen in equal numbers. Blood culture grew Salmonella paratyphi A in 1
      case. Splenic aspirate culture was positive in 3 (Escherichia coli [1], S
      paratyphi A [1], Acinetobacter [1]). Widal serology was positive in 9 (50%)
      patients. Management consisted of intravenous broad-spectrum antibiotic therapy
      in all patients, together with percutaneous aspiration in 10 (56%) cases where
      the abscess size was greater than 3 cm. All patients responded, and complete
      resolution was observed. CONCLUSION: Isolated SA in children responds favorably
      to conservative treatment with intravenous broad-spectrum antibiotics and
      percutaneous drainage without the need for splenectomy.

PMID- 20152355
TI  - Long-term outcomes after hepaticojejunostomy for choledochal cyst: a 10- to 27
      year follow-up.
AB  - INTRODUCTION: Choledochal cyst (CC) is closely associated with anomalous
      arrangement of the pancreaticobiliary duct, which is considered a high-risk
      factor for biliary tract malignancy. Early diagnosis and early treatment for CC
      could lead to a good prognosis. This study investigated late complications and
      long-term outcomes after surgery for CC. PATIENTS AND METHODS: Fifty-six patients
      with CC and over 10 years of postoperative follow-up were analyzed
      retrospectively. All patients had undergone total resection of the extrahepatic
      bile duct and hepaticojejunostomy. RESULTS: Six patients showed liver dysfunction
      manifested in the first 10 years after surgery, but all returned to normal
      thereafter. Dilatation of intrahepatic bile ducts persisted in 6 postoperatively,
      and in 3, this was still apparent more than 10 years after. Recurrent abdominal
      pain was encountered in 3, 1 had pancreas divisum with a pancreatic stone, and 1
      had adhesive small bowel obstruction. Two patients developed biliary tract
      malignancy. A 14-year-old girl died of recurrent common bile duct cancer 2 years
      after the initial resection of CC with adenocarcinoma. A 26-year-old man with
      repeated cholangitis owing to multiple intrahepatic bile stones developed
      cholangiocarcinoma 26 years after the initial resection of CC. Event-free
      survival rate and overall survival rate were 89% (50/56) and 96% (54/56),
      respectively. CONCLUSIONS: Choledochal cyst generally has an excellent prognosis
      with early total resection and reconstruction. Long-term surveillance for the
      development of malignancy is still essential, especially if there is ongoing
      dilatation of the intrahepatic bile duct or biliary stones.

PMID- 20152356
TI  - Intraoperative endoscopy during choledochal cyst excision: extended long-term
      follow-up compared with recent cases.
AB  - INTRODUCTION: We routinely perform intraoperative endoscopy (IOE) of the
      intrahepatic bile duct (IHBD) and intrapancreatic bile duct (IPBD) with a
      pediatric cystoscope during excision of choledochal cyst (CC). Here we compare
      extended long-term follow-up patients with a series of recent cases. METHODS: We
      compared 25 CC patients treated over the past 5 years (group 1) with 69 CC
      patients treated between 1986 and 1998 and followed up for more than 10 years
      (group 2), focusing on stone formation. RESULTS: In group 1 (mean follow-up, 2.6
      years) IOE identified IHBD debris in 7 (28%) of 25 and IPBD protein plugs in 9
      (36%) of 25. In group 2 (mean follow-up, 14.6 years) IOE identified IHBD debris
      in 11 (16%) of 69 and IPBD protein plugs in 17 (25%) of 69. There was no relation
      between type of CC and incidence of IHBD debris or IPBD protein plugs. The
      incidence of postoperative stones to date is 0% in group 1 and 2.9% in group 2,
      rates far lower than those reported in the literature. CONCLUSIONS: We attribute
      our lower incidence of stones directly to IOE and recommend that it be performed
      routinely during cyst excision. It is simple, is effective, and improves outcome.

PMID- 20152357
TI  - Childhood phaeochromocytoma and paraganglioma: 100% incidence of genetic
      mutations and 100% survival.
AB  - INTRODUCTION: The aim is to identify the incidence of genetic mutations and
      outcome of children presenting with phaeochromocytoma/paraganglioma (PGL) to a
      single paediatric surgical service to determine the need for genetic counselling
      in associated kindreds. METHODS: A retrospective case note review was undertaken
      of all cases treated between 1998 and 2008 with particular reference to
      presentation, management, and predisposing genetic conditions. RESULTS: Seven
      cases (4 male, 3 female) were identified (median age, 13 years; interquartile
      range, 9-16). Three cases had a family history of phaeochromocytoma/PGL. All
      presented with neurologic symptoms related to hypertension, including headaches
      (n = 5), hemiparesis (n = 2), facial palsy, and hemianopia. All underwent
      surgical resection. Five patients had meta-iodobenzylguanidine (MIBG) therapy for
      apparently malignant features. All cases were found to have a predisposing
      genetic mutation: von Hippel-Lindau (n = 3), succinate dehydrogenase mutations (n
      = 3), and multiple endocrine neoplasia (n = 1). All patients are alive after a
      median follow-up of 5 (interquartile range, 2-7) years. CONCLUSIONS: All 7 cases
      had a familial genetic mutation identified, and none arose de novo. We advocate
      genetic counselling for all families of children diagnosed with
      phaeochromocytoma/PGL with lifelong surveillance tailored to the underlying
      syndrome because of the increased risk of synchronous and metachronous tumours
      associated with these genetic syndromes.

PMID- 20152358
TI  - Increased expression of the hedgehog signaling pathway in pediatric solid
      malignancies.
AB  - PURPOSE: The activation of the hedgehog (Hh) signaling is involved in the
      progression of various cancers. However, the correlation between the Hh signaling
      and tumorigenesis of pediatric malignancies has not been well documented. The
      present study was undertaken to examine the expression of the Hh signaling
      pathway in various pediatric tumors to elucidate the role of Hh signaling in
      pediatric malignancies. METHODS: Surgical specimens were obtained from 68
      patients with pediatric malignancies (neuroblastoma, 25; rhabdomyosarcoma, 18;
      hepatic tumor, 12; and renal tumor, 13). The expression of sonic hedgehog (Shh),
      its receptor Patched (Ptch), and downstream transcription factor Gli1 was
      evaluated using immunohistochemical staining. RESULTS: In neuroblastoma, 96%,
      100%, and 68%; in rhabdomyosarcoma, 78%, 100%, and 78%; in Wilms' tumor, 71%,
      100%, and 43%; and in hepatoblastoma, 100%, 100%, and 73% of the specimens
      stained positive for Shh, Ptch, and Gli1, respectively. Differentiated
      neuroblastoma cells showed more intense Gli1 expression than in immature
      neuroblastoma cells. In rhabdomyosarcoma, the expression of Gli1 was higher in
      alveolar type than in embryonal type. CONCLUSIONS: These findings suggest that
      the Shh-Ptch1-Gli1 signaling pathways are frequently activated in most pediatric
      malignant tumors. The Hh signaling pathway may therefore play an important role
      in the differentiation and malignant potential of pediatric malignancies.

PMID- 20152359
TI  - Familial associations in medullary thyroid carcinoma with Hirschsprung disease:
      the role of the RET-C620 "Janus" genetic variation.
AB  - INTRODUCTION: Hirschsprung disease (HSCR) is associated with the later
      development of multiple endocrine neoplasia (MEN2), because RET gene variations
      are associated with both conditions. Specifically, HSCR-MEN2 cosegregation mostly
      relates to the cysteine-rich area at the RET-620 (the "Janus gene"). AIM: The aim
      of this study was to explore the clinical and genetic associations of HSCR-MEN2
      in a cohort of HSCR patients. METHODS: RET gene variation was evaluated by
      heteroduplex single-strand conformational polymorphism analysis and validated
      with automated sequencing techniques in HSCR patients (including 18 kindreds).
      Those with RET C620 variations were subjected to familial evaluation for
      coexisting HSCR-MEN2. RESULTS: A cohort of 118 patients with HSCR (n = 89) or
      medullary thyroid carcinoma (n = 29) were studied, including 3 families where a
      RET-620 point mutation was identified. No C618, C609, or C611 variations were
      detected. In 1 remarkable 6-generational family (family 3), HSCR in early
      generations seemed to be later replaced by MEN2A. In the other 2 families with
      total colonic aganglionosis, a relative with a medullary thyroid carcinoma was
      identified. CONCLUSION: Gene mutation in the RET-620 position carries significant
      risk and may be part of a targeted investigation of high-risk areas in HSCR. We
      propose an alternative hypothesis of endoplasmic reticulum control to explain the
      changing phenotypic expression.

PMID- 20152360
TI  - Intraoperative measurement of rectourethral fistula: prevention of incomplete
      excision in male patients with high-/intermediate-type imperforate anus.
AB  - INTRODUCTION: We report a novel technique to measure the length of the
      rectourethral fistula (RUF) in male patients with high-/intermediate-type
      imperforate anus during laparoscopically assisted anorectal pull-through (LAARP)
      to prevent incomplete excision. METHOD: During LAARP for RUF in 5 male patients
      (mean age, 4.6 months; prostatic in 3, bulbar in 2), the RUF was dissected
      carefully close to the urethra and opened; and a fine catheter with 10-mm
      calibrations was inserted by the laparoscopic surgeon until it was seen to emerge
      at or near the verumontanum by another surgeon performing cystoscopy. The
      laparoscopic surgeon then measured the distance from the point where dissection
      was ceased at the rectal end to the urethral orifice. The RUF was dissected free
      from the prostate for exactly this length, tied, and excised; and colon pull
      through was performed to finish LAARP. RESULT: Rectourethral fistulae ranged from
      5 to 15 mm and were much longer than expected. All dissections were uncomplicated
      without any injury to the urethra, and postoperative courses were unremarkable.
      At mean follow-up of 11 months, urination is normal in all without evidence of
      residual fistula. CONCLUSION: Knowing the exact length of the RUF facilitates
      safe and complete excision in an otherwise blind situation.

PMID- 20152361
TI  - Operative vs nonoperative management of blunt pancreatic trauma in children.
AB  - PURPOSE: The aim of this study was to evaluate the outcome of nonoperative vs
      operative management of blunt pancreatic trauma in children. METHODS:
      Retrospective review of pancreatic injuries from 1995 to 2006 at an urban level I
      regional pediatric trauma center. RESULTS: Forty-three children with pancreatic
      injury were included in the analysis. Injuries included grade I (n = 18), grade
      II (n = 6), grade III (n = 17), and grade IV (n = 2). For grade II to IV
      injuries, patients managed operatively (n = 14) and nonoperatively (n = 11) had
      similar lengths of stay and rates of readmission, despite increased pancreatic
      complications (PCs) in the nonoperative cohort (21% vs 73%; P = .02). There was a
      trend toward increased non-PCs in patients managed with resection (P = .07).
      Twelve patients underwent successful diagnostic endoscopic retrograde
      cholangiopancreatography in which duct injury was identified. In this group,
      nonoperative management was pursued in 6 patients but was associated with
      increased rates of PC (86% nonoperative vs 29% operative; P = .02). CONCLUSIONS:
      Operative management of children with grades II to IV pancreatic injury results
      in significantly decreased rates of PCs but fails to decrease length of stay in
      the hospital, possibly as a result of non-PCs. Endoscopic retrograde
      cholangiopancreatography may serve as a useful diagnostic modality for guiding
      operative vs nonoperative management decisions.

PMID- 20152362
TI  - Urinomas protect renal function in posterior urethral valves--a population based
      study.
AB  - BACKGROUND/PURPOSE: Urinomas have been thought to protect renal function in boys
      with posterior urethral valves (PUVs), although recent reports have disputed
      this. This study tested the hypothesis that urinomas protect global renal
      function in boys with PUV. METHODS: A retrospective analysis of all boys with PUV
      presenting to a tertiary unit derived from a region with an estimated population
      of 5.5 million was performed. Comparisons of the initial nadir creatinine,
      current creatinine, and renal status score (RSS) were made between those with and
      without urinomas. The RSS was derived from nephrology assessment of current renal
      status (0 = normal to 4 = end-stage renal failure or transplantation). Results
      were given as median (range), except for RSS, which was given as mean +/- SEM. P
      < or = .05 was regarded as significant. RESULTS: During 1989-2009, 9 of 89 PUV
      boys were diagnosed with urinomas. Initial nadir creatinine was statistically
      lower in boys with urinomas (31 [18-44] vs 45 [20-574] mumol/L, P < .01). Length
      of follow-up was similar (5.1 [2.2-17.3] vs 5.9 [1.8-19.7] years, P = .59).
      Follow-up creatinine was significantly lower in urinoma boys (44 [25-77] vs 61
      [29-1227] micromol/L, P < .05), as was the RSS (0.14 +/- 0.14 vs 0.91 +/- 0.14, P
      < .01). No urinoma boys progressed to end-stage renal failure or required
      transplant. CONCLUSION: This population-based study of PUV boys demonstrates that
      urinomas reduce nadir creatinine and significantly protect long-term global renal
      function.

PMID- 20152363
TI  - Late hormonal function after testicular torsion.
AB  - INTRODUCTION: Testicular torsion may be an important cause of male infertility.
      We aimed to investigate the late hormonal function in patients with testicular
      ischemia/reperfusion injury of the testis after orchidectomy or detorsion.
      METHODS: Twenty patients (mean age, 13.6 years) were prospectively evaluated at a
      mean of 5 years after testicular torsion. The serum follicle-stimulating hormone,
      luteinizing hormone (before and after gonadotropin-releasing hormone
      stimulation), testosterone, and inhibin B were measured. Fifteen age-matched
      adolescents without evidence of endocrine disease were used as controls for
      inhibin B values. Data are quoted as mean +/- SEM. RESULTS: Twelve patients were
      treated with detorsion and orchidopexy, and 8 underwent orchidectomy. Serum
      follicle-stimulating hormone, luteinizing hormone, and testosterone were all
      within the reference range. Inhibin B levels were significantly reduced in the 2
      groups compared with the controls (34.5 +/- 5.2 vs 63.9 +/- 12.8 pg/mL, P = .02),
      but were not significantly different between the orchidectomy group and the group
      that underwent detorsion (41.3 +/- 9.7 vs 30.4 +/- 5.9 pg/mL, P = .41).
      CONCLUSION: Hormonal testicular function can be compromised after testicular
      torsion, although the type of surgery (orchidectomy or orchidopexy) does not seem
      to change the effect of this ischemia/reperfusion injury.

PMID- 20152364
TI  - Hidden in plain sight: the mammary line in males may be the missing link
      regulating inguinoscrotal testicular descent.
AB  - BACKGROUND/PURPOSE: Inguinoscrotal testicular descent is controlled by androgens
      and the genitofemoral nerve, but the trigger for what makes the gubernaculum
      become a migratory organ like a limb bud remains unknown. Recent observations in
      the flutamide-treated rat suggested a link with the mammary line. We aimed,
      therefore, to reassess histologic anatomy in 2 different rodent models of
      androgen blockade, the testicular feminisation mouse (TFM) and the flutamide
      treated rat. METHODS: Neonatal TFM mice and fetal and neonatal rats after
      pretreatment of dams with an antiandrogen, flutamide (75 mg/kg; sunflower oil;
      days 16-19), were prepared for histologic analysis of the inguinal region and
      compared with fetal and neonatal controls. RESULTS: Fetal control rats (E15.5
      days) showed a mammary bud just outside the future inguinal canal adjacent to the
      gubernaculum. Neonatal TFM mice showed persistence of the inguinal breast bud
      supplied by the genitofemoral nerve. Flutamide-treated rats (D2) showed the
      gubernaculum surrounded by a persisting breast bud. CONCLUSIONS: The inguinal
      mammary line is adjacent to the gubernaculum in fetal rodents, and after androgen
      blockade, the gubernaculum becomes connected to the breast. The male mammary
      line, which is hidden in plain sight outside the inguinal canal, is made visible
      by androgen blockade. It may be the missing link in testicular descent,
      regulating gubernacular migration.

PMID- 20152365
TI  - A dedicated consultant-led vascular access team significantly reduces out-of
      hours and emergency permanent central venous access insertions.
AB  - PURPOSE: The insertion of a permanent central venous access device (PCVAD i.e.
      Broviac or Hickman lines and vascuports) is often considered a low priority and
      performed as an emergency. In 2004, a vascular access team (VAT), responsible for
      all PCVAD insertions, was established in our institution to address this.
      METHODS: Data were collected retrospectively on all PCVAD insertions in 2 periods
      (January 2002-December 2003 and January 2005-December 2006). This included
      procedure, list type, surgeon grade, and operative time. RESULTS: During 2002 to
      2003 and 2005 to 2006, 465 and 569 PCVADs were inserted, respectively (22%
      increase). After introduction of the VAT, the percentage of lines inserted during
      emergency lists fell from 24% (n = 112) to 13% (n = 72), and out-of-hours fell
      from 6% (n = 29) to 3% (n = 17; P < .05), respectively. Median time taken for
      PCVAD insertion in 2005 to 2006 was significantly less if using an elective list
      compared with insertions performed on an emergency list (elective, 67 [56-82]
      minutes vs emergency, 85 (65-110) minutes; P < .05). DISCUSSION: Introduction of
      a VAT has led to a significant decrease in emergency and out-of-hours PCVAD
      insertions, despite an increase in overall activity for the period. The median
      time taken for elective insertions is significantly less than emergency
      insertions, which has increased the efficiency of vascular access provision at
      our institution.

PMID- 20152366
TI  - Summary of the 56th BAPS and 10th EUPSA Congress: Graz, Austria 17th-20th June
      2009.
AB  - This is a summary of the annual summer meeting that was a combination of two of
      the largest European paediatric surgical associations.

PMID- 20152367
TI  - Diagnosis and management of fetal intrapericardial Morgagni diaphragmatic hernia
      with massive pericardial effussion.
AB  - Herniation of the liver into the fluid-filled pericardial sac resulting in a
      thoracic mass is a particularly rare form of Morgagni hernia (congenital
      diaphragmatic hernia of Morgagni). We report an early antenatal diagnosis of
      congenital diaphragmatic hernia of Morgagni with pericardium effussion at 21
      weeks' gestation. Two pericardiocentesis were performed at 21 and 22 4/7 weeks'
      gestation because of recurrence of pericardial effussion. Regular ultrasound
      assessments showed progressive herniation of the liver to practically fill the
      right hemithorax. An ex utero intrapartum treatment procedure was performed at 37
      weeks' gestation to rescue maximum intrathoracic space for ventilation of the
      remaining functional lung tissue and to establish an airway for postnatal
      support. After birth, the patient successfully underwent early correction of the
      hernia. Postoperative course was uneventful, and the newborn girl was discharged
      18 days later without complications and is currently doing well.

PMID- 20152368
TI  - Thoracoscopic pneumonectomy for communicating bronchopulmonary foregut
      malformation in a 4-month-old child.
AB  - Thoracoscopic total pneumonectomy has recently been described in the pediatric
      literature for the first time (Anselmo D, Perez I, Shaul D. Thoracoscopic
      Pneumonectomy for Severe Bronchiectasis in a 9-Year-Old Female. J Laparoendosc
      Adv Surg Tech 2008;18:775-777). In this article, we describe the use of
      thoracoscopic pneumonectomy in a 4-month-old boy with a complete (entire left
      lung) communicating bronchopulmonary foregut malformation. The patient is a 4
      month-old boy who presented with persistent cough and low-grade fever. Chest
      radiograph was performed and showed a diffuse infiltrative pattern in the left
      lung. Computed tomography was then performed and revealed a poorly aerated
      abnormal left lung with absence of the left main stem bronchus. Subsequently, the
      patient underwent an upper gastrointestinal (UGI) series, which demonstrated that
      the left main stem bronchus arose from the distal esophagus and had no
      communication with the trachea. The patient tolerated a left thoracoscopic
      pneumonectomy very well. On postoperative day 5, a UGI demonstrated a question of
      a small contained leak. Therefore, a repeat study was performed 1 week later and
      did not demonstrate a leak. He was discharged in good health. Communicating
      bronchopulmonary foregut malformations are rare anomalies that require resection
      of the anomalous lung segment. This can be safely performed with a thoracoscopic
      technique even if it requires a pneumonectomy.

PMID- 20152369
TI  - Visceral myopathy causing chronic intestinal pseudoobstruction and intestinal
      failure in a child with Sanjad-Sakati syndrome.
AB  - Sanjad-Sakati syndrome is a rare autosomal recessive disorder mainly occurring in
      the Arab Peninsula. This condition is associated with metabolic and septic
      complications starting in the neonatal period. Chronic intestinal
      pseudoobstruction owing to visceral myopathy is a rare disabling condition. We
      report a rare concurrence of Sanjad-Sakati syndrome and chronic intestinal
      pseudoobstruction in a Saudi child complicated by intestinal failure, sepsis, and
      early mortality.

PMID- 20152370
TI  - Congenital subcostal hernia with unusual contents.
AB  - Congenital hernias arising in the subcostal region are rare. We describe a case
      of a former preterm infant, born with congenitally fused right 11th and 12th ribs
      and a protuberant mass in the right subcostal region. This mass was associated
      with a small fascial defect and herniation of abdominal contents. At operation,
      the mass was determined to be a hernia with an incarcerated ovarian remnant and
      fallopian tube.

PMID- 20152371
TI  - Congenital and acquired mesocolic hernias presenting with small bowel obstruction
      in childhood and adolescence.
AB  - OBJECTIVE: The objective was to present a case series of pediatric patients
      presenting with small bowel obstruction secondary to both congenital and acquired
      internal mesocolic hernias, and the use of imaging technology in the management
      of this condition. METHODS: A retrospective review of patients treated at the
      Yale-New Haven Children's Hospital for small bowel obstruction from 1998 to 2008
      (n = 6) who presented with acute small bowel obstruction secondary to internal
      mesocolic hernias was performed. RESULTS: We present 6 patients with small bowel
      obstruction caused by congenital (n = 4) and acquired (n = 2) mesocolic hernias
      after previous surgery. The median age at presentation was 13 years. Small bowel
      obstruction with a mesocolic hernia was identified by preoperative abdominal
      computerized tomography in 3 patients (50%) and at operation in the others. The
      mean length of stay was 6 days, with no recurrent episodes in the follow-up
      period. CONCLUSION: Small bowel obstruction secondary to mesocolic hernias,
      although rare, may be considered in the differential diagnosis of patients with
      history of malrotation or abdominal wall defects owing to their association with
      congenital mesenteric anomalies. This condition requires special attention from
      the clinician because of its catastrophic consequences. Imaging studies are an
      important asset because of the difficulty in making an accurate clinical
      diagnosis and the rarity of internal hernias.

PMID- 20152372
TI  - Gallbladder duplication: evaluation, treatment, and classification.
AB  - Duplicate gallbladder is a rare congenital anomaly resulting from abnormalities
      in embryogenesis during the fifth and sixth weeks of gestation. Approximately 210
      cases have been described. Variations include duplicate, triplicate, and septated
      gallbladder. We encountered a 15-year-old girl with both a duplicated gallbladder
      and a duplicated cystic duct who underwent successful laparoscopic
      cholecystectomy. This combination is extremely unusual, and based upon our
      findings in this case and a review of the literature, we propose the Unified
      Classification of Multiple Gallbladders.

PMID- 20152373
TI  - Vascular endothelial growth factor and bladder from a different perspective: not
      only an angiogenic factor.
AB  - Angiogenesis has a key role for embryonic development and is crucial in several
      major diseases. Molecular basis of angiogenesis has been widely investigated (J
      Biochem Mol Biol. 2006;39:469-478, Oncogene. 2000;19:5598-5605). In this review,
      vascular endothelial growth factor (VEGF) and related receptors and their key
      roles in embryonic bladder development are discussed. The normal VEGF expression
      and related angiogenesis pattern of embryonic bladder are highlighted. The VEGF
      family especially VEGF-A is the major player in angiogenesis as well as many
      other angiogenic factors and activates 2 tyrosine kinase receptors, VEGFR-1 and
      VEGFR-2 (J Biochem Mol Biol. 2006;39:469-478). Besides its worthy role in
      angiogenesis, VEGF-A also seems to participate in normal bladder development (J
      Urol. 2007;177:1552-1557, Br J Urol Int. 2006;98:217-225). In previous studies,
      we have shown that exogenous VEGF or hypoxia-induced endogenous upregulation of
      this protein accelerates the growth of the bladder by detrusor and urothelium
      hypertrophy and hyperplasia (J Urol. 2007;177:1552-1557, Br J Urol Int.
      2006;98:217-225, Dev Biol. 1997;183:139-149, Neurourol Urodyn. 2004;23:342-348).
      This abrupt role of VEGF on detrusor muscle through a hypoxic pathway may
      potentially be a part of the solution for many urologic conditions such as
      remodeling of detrusor muscle in antenatal bladder outlet obstruction.

PMID- 20152374
TI  - Proboscis lateralis with ipsilateral sinonasal and olfactory pathway aplasia.
AB  - Proboscis lateralis is a rare craniofacial malformation characterized by absence
      of nasal cavity on one side with a trunk-like nasal appendage protruding from
      superomedial portion of the ipsilateral orbit. High-resolution computed
      tomography and magnetic resonance imaging are extremely useful in evaluating this
      congenital condition and the wide spectrum of associated anomalies occurring in
      the surrounding anatomical regions and brain. We present a case of proboscis
      lateralis in a 2-year-old girl with associated ipsilateral sinonasal aplasia,
      orbital cyst, absent olfactory bulb and olfactory tract. Absence of ipsilateral
      olfactory pathway in this rare disorder has been documented on high-resolution
      computed tomography and magnetic resonance imaging by us for the first time in
      English medical literature.

PMID- 20152375
TI  - A simple technique to enhance the safety of abscess aspirations.
AB  - Tapping and aspirating abscesses or fluid collections in children can be
      difficult and even hazardous. A simple technique is described based on limiting
      the depth of penetration of the needle. This is achieved by removing the tubular
      plastic needle cover (or cap), cutting it to a predetermined length and replacing
      it. Thus, the cap acts as a "stopper." In addition, this approach allows the
      operator to perform the task with only 1 hand on the syringe-needle unit.

PMID- 20152376
TI  - Infantile fibrosarcoma of the ileum presenting with congenital bowel obstruction.

PMID- 20152377
TI  - Letter to the editor regarding single-site laparoscopic gastrostomy in children.

PMID- 20152380
TI  - Historical review by Dr Raffensperger about Pierre Fredet and pyloromyotomy
      speculates about the naming of the procedure.

PMID- 20152382
TI  - An overview on the accumulation, distribution, transformations, toxicity and
      analytical methods for the monitoring of persistent organic pollutants.
AB  - Recent years have seen an upsurge of interest in developing low cost and reliable
      methods for the detection and precise determination of ultra-trace concentrations
      of persistent organic pollutants (POPs), because of their bioaccumulation,
      transformation and toxicity. Therefore, a comprehensive review with 108
      references referring to the distribution, source, accumulation, transformation,
      types and toxicity of polychlorinated biphenyls (PCBs) and organochlorine
      pesticides (OCPs) is presented. The review also aims to highlight on the current
      best practices for the analysis of PCBs and OCPs. Moreover, with the signing of
      the Stockholm convention on POPs and the development of global monitoring
      programs, there is an increased need for laboratories in developing countries to
      determine such class of chemicals. A major focus revealed the need for low cost
      methods that can be implemented easily in developing countries such as
      electrochemical techniques.

PMID- 20152383
TI  - Application of porphyrins in flow-injection analysis: a review.
AB  - Porphyrins and metalloporphyrins fulfil a very important role in the metabolism
      of living organisms through biological pigments or biochromes and are therefore
      also employed in numerous applications in analytical chemistry. In flow-injection
      analysis the role of porphyrins and metalloporphyrins are centered as either that
      of analyte or that of a reagent or modifier in the determination of other
      species. This paper covers the attributes of porphyrin and metallophorphyrin
      complexes as enhancements in chemical analysis in flow-injection systems and
      points out the advantages and disadvantages in the implementation thereof.

PMID- 20152384
TI  - Determination of colloidal and dissolved silver in water samples using
      colorimetric solid-phase extraction.
AB  - The increase in bacterial resistance to antibiotics has led to resurgence in the
      use of silver as a biocidal agent in applications ranging from washing machine
      additives to the drinking water treatment system on the International Space
      Station (ISS). However, growing concerns about the possible toxicity of colloidal
      silver to bacteria, aquatic organisms and humans have led to recently issued
      regulations by the US EPA and FDA regarding the usage of silver. As part of an
      ongoing project, we have developed a rapid, simple method for determining total
      silver, both ionic (silver(I)) and colloidal, in 0.1-1mg/L aqueous samples, which
      spans the ISS potable water target of 0.3-0.5mg/L (total silver) and meets the US
      EPA limit of 0.1mg/L in drinking water. The method is based on colorimetric solid
      phase extraction (C-SPE) and involves the extraction of silver(I) from water
      samples by passage through a solid-phase membrane impregnated with the
      colorimetric reagent DMABR (5-[4-(dimethylamino)benzylidene]rhodanine). Silver(I)
      exhaustively reacts with impregnated DMABR to form a colored compound, which is
      quantified using a handheld diffuse reflectance spectrophotometer. Total silver
      is determined by first passing the sample through a cartridge containing Oxone,
      which exhaustively oxidizes colloidal silver to dissolved silver(I). The method,
      which takes less than 2 min to complete and requires only approximately 1 mL of
      sample, has been validated through a series of tests, including a comparison with
      the ICP-MS analysis of a water sample from ISS that contained both silver(I) and
      colloidal silver. Potential earth-bound applications are also briefly discussed.

PMID- 20152385
TI  - Dispersive liquid-liquid microextraction versus single-drop microextraction for
      the determination of several endocrine-disrupting phenols from seawaters.
AB  - Two liquid-phase microextraction procedures: single-drop microextraction (SDME)
      and dispersive liquid-liquid microextraction (DLLME), have been developed for the
      determination of several endocrine-disrupting phenols (EDPs) in seawaters, in
      combination with high-performance liquid chromatography (HPLC) with UV detection.
      The EDPs studied were bisphenol-A, 4-cumylphenol, 4-tertbutylphenol, 4
      octylphenol and 4-n-nonylphenol. The optimized SDME method used 2.5 microL of
      decanol suspended at the tip of a micro-syringe immersed in 5 mL of seawater
      sample, and 60 min for the extraction time. The performance of the SDME is
      characterized for average relative recoveries of 102+/-11%, precision values
      (RSD)<9.4% (spiked level of 50 ng mL(-1)), and detection limits between 4 and 9
      ng mL(-1). The optimized DLLME method used 150 microL of a mixture
      acetonitrile:decanol (ratio 15.7, v/v), which is quickly added to 5 mL of
      seawater sample, then subjected to vortex during 4 min and centrifuged at 2000
      rpm for another 5 min. The performance of the DLLME is characterized for average
      relative recoveries of 98.7+/-3.7%, precision values (RSD)<7.2% (spiked level of
      20 ng mL(-1)), and detection limits between 0.2 and 1.6 ng mL(-1). The
      efficiencies of both methods have also been compared with spiked real seawater
      samples. The DLLME method has shown to be a more efficient approach for the
      determination of EDPs in seawater matrices, presenting enrichment factors ranging
      from 123 to 275, average relative recoveries of 110+/-11%, and precision values
      (RSD)<14%, when using a real seawaters (spiked level of 3.5 ng mL(-1)).

PMID- 20152386
TI  - Analysis of ammonia and aliphatic amines in environmental water by micellar
      electrokinetic chromatography and QSPR modeling of electrophoretic migration
      time.
AB  - In this paper, a rapid and sensitive method for the determination of ammonia and
      22 aliphatic amines derivatized was established by cyclodextrin (CD) modified
      micellar electrokinetic chromatography with laser-induced fluorescence detection
      using 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole as a derived reagent. By a series
      of unvaried studies, the best conditions were selected using 20mM tetraborate (pH
      9.70) containing 25 mM SDS, 7 mM beta-CD, 10% acetonitrile, 0.5M urea, and
      applied voltage 25 kV. Under the optimum conditions, ammonia and 22 aliphatic
      amines were separated successfully in 19 min. The signal response was linear over
      three-order of concentrations. The intra-day and inter-day relative standard
      deviations (RSD) were less than 0.81% and 1.00% for migration times, 1.76% and
      2.01% for peak areas. Limits of detection (LOD) for the analytes was (S/N=3)
      approximate 10(-9)-10(-12)M. The method was applied to the determination of
      ammonia and aliphatic amines in environmental water with recoveries in the range
      of 90.2-110.8%. In addition, a quantitative structure-property relationship
      (QSPR) model for the estimation of the electrophoretic migration time was
      established with the comprehensive descriptors for structural and statistical
      analysis (CODESSA) program for the first time. The multilinear regression (MLR)
      equation contained two theoretical descriptors and had the following statistical
      indices: R(2)=0.9668, F=290.7839, R(cv)(2)=0.9576 and S(2)=0.8149.

PMID- 20152387
TI  - Gold nanoparticle-based colorimetric sensor for studying the interactions of beta
      amyloid peptide with metallic ions.
AB  - In this paper, a kind of beta-amyloid peptide (Abeta1-16) conjugated gold
      nanoparticles (Abeta1-16@GNPs) are prepared and employed as colorimetric
      indicator for studying the interaction of beta-amyloid peptide with metallic ions
      (e.g. Zn(2+) and Ca(2+)). In the presence of Zn(2+), mono-dispersing Abeta1
      16@GNPs enable to form aggregates or attach on the SHG-44 (human glioma cell)
      cellular surface which results in significant color change of the solution. The
      experimental results indicate that Zn(2+) can interact with Abeta1-16 and form
      Zn(2+)-beta-amyloid peptide complexes. In particular, in the presence of Zn(2+),
      a time-dependent interaction of cells with Abeta1-16@GNPs has been observed that
      may suggest different expression levels of beta-amyloid peptide related proteins
      in various cell cycles. In addition, the aggregating/binding process can be
      easily reversed by adding EDTA, a good chelated ligand of Zn(2+), which gives
      further proof of the interaction mechanism.

PMID- 20152388
TI  - A sensitive and highly stable electrochemical impedance immunosensor based on the
      formation of silica gel-ionic liquid biocompatible film on the glassy carbon
      electrode for the determination of aflatoxin B1 in bee pollen.
AB  - The paper describes a sensitive and highly stable label-free electrochemical
      impedance immunosensor for the determination of aflatoxin B(1) (AFB(1)), which is
      based on the formation of silica gel-ionic liquid biocompatible film on the
      glassy carbon electrode. The electrochemical performances of the sensor were
      investigated by electrochemical impedance spectroscopy using a Fe(CN)(6)(3-/4-)
      phosphate buffer solution as base solution for test. As new ionic liquid, 1-amyl
      2,3-dimethylimidazolium hexafluorophosphate, offers a very biocompatible
      microenvironment for AFB(1) antibody, the sensor exhibits good repeatability
      (RSD=1.2%), sensitive electrochemical impedance response to AFB(1) in the range
      of 0.1-10 ng ml(-1) and lowers the detection limit of AFB(1) (0.01 ng ml(-1)).
      The electron-transfer resistance change of the sensor after and before incubation
      with AFB(1) of 2.0 ng ml(-1) can retain 95% over a 180-day storage period at 4
      degrees C. The results present a remarkable improvement of sensitivity (2-fold)
      and long-term stability (190-fold) when compared to classical silica gel sensor.
      Moreover, proposed sensor has a high selectivity to AFB(1) alone with no
      significant response to AFB(2), AFG(1), AFG(2) and AFM(1) as single substrates,
      it has been successfully applied to the determination of trace AFB(1) in bee
      pollen samples with a spiked recovery in the range of 96.0-102.5%.

PMID- 20152389
TI  - Temperature-controlled ionic liquid-liquid-phase microextraction for the pre
      concentration of lead from environmental samples prior to flame atomic absorption
      spectrometry.
AB  - Hydrophobic ionic liquid could be dispersed into infinite droplets under driving
      of high temperature, and then they can aggregate as big droplets at low
      temperature. Based on this phenomenon a new liquid-phase microextraction for the
      pre-concentration of lead was developed. In this experiment, lead was transferred
      into its complex using dithizone as chelating agent, and then entered into the
      infinite ionic liquid drops at high temperature. After cooled with ice-water bath
      and centrifuged, lead complex was enriched in the ionic liquid droplets.
      Important parameters affected the extraction efficiency had been investigated
      including the pH of working solution, amount of chelating agent, volume of ionic
      liquid, extraction time, centrifugation time, and temperature, etc. The results
      showed that the usually coexisting ions containing in water samples had no
      obvious negative effect on the recovery of lead. The experimental results
      indicated that the proposed method had a good linearity (R=0.9951) from 10 ng mL(
      1) to 200 ng mL(-1). The precision was 4.4% (RSD, n=6) and the detection limit
      was 9.5 ng mL(-1). This novel method was validated by determination of lead in
      four real environmental samples for the applicability and the results showed that
      the proposed method was excellent for the future use and the recoveries were in
      the range of 94.8-104.1%.

PMID- 20152390
TI  - Detection of T4 DNA ligase using a solid-state electrochemiluminescence
      biosensing switch based on ferrocene-labeled molecular beacon.
AB  - A solid-state electrochemiluminescence (ECL) biosensing switch based on special
      ferrocene-labeled molecular beacon (Fc-MB) has been successfully developed for T4
      DNA ligase detection. Such special switch system consisted of two main parts, an
      ECL substrate and an ECL intensity switch. The ECL substrate was made by
      modifying the complex of Au nanoparticle and Ruthenium (II) tris-(bipyridine)
      (Ru(bpy)(3)(2+)-AuNPs) onto Au electrode. A molecular beacon labeled by ferrocene
      as the ECL intensity switch. The molecular beacon is designed with special base
      sequence, which could combine with its target biomolecule via the reaction of the
      repair and recombination of nucleic acids by DNA ligase. During the reaction, the
      molecular beacon opened its stem-loop, and the labeled Fc was consequently kept
      away from the ECL substrate. Such structural change resulted in an obvious
      increment in ECL intensity due to the decreased Fc quenching effect to the ECL
      substrate. The analysis results are sensitive and specific.

PMID- 20152391
TI  - Non-enzymatic electrochemical CuO nanoflowers sensor for hydrogen peroxide
      detection.
AB  - The electrocatalytic activity of a CuO flower-like nanostructured electrode was
      investigated in terms of its application to enzyme-less amperometric H(2)O(2)
      sensors. The CuO nanoflowers film was directly formed by chemical oxidation of
      copper foil under hydrothermal condition and then used as active electrode
      material of non-enzymatic electrochemical sensors for H(2)O(2) detection under
      alkaline conditions. The sensitivity of the sensor with CuO nanoflowers electrode
      was 88.4 microA/mM cm(2) with a linear response in the range from 4.25 x 10(-5)
      to 4 x 10(-2)M and a detection limit of 0.167 microM (S/N=3). Excellent
      electrocatalytic activity, large surface-to-volume ratio and efficient electron
      transport property of CuO nanoflowers electrode have enabled stable and highly
      sensitive performance for the non-enzymatic H(2)O(2) sensor.

PMID- 20152392
TI  - Au nanoparticle decorated silicate network for the amperometric sensing of
      isoniazid.
AB  - Au nanoparticle (nAu) based electrochemical platform for the amperometric sensing
      of isoniazid at sub-nanomolar level is developed. The sol-gel derived 3
      dimensional silicate network pre-assembled on a conducting substrate is
      chemically decorated with nAu of 70-100 nm by seed-mediated growth approach. The
      Au nanoseeds are first chemisorbed onto the thiol functional groups of the
      silicate network and their size was enlarged by hydroxylamine seeding. The
      nanoparticles efficiently catalyze the oxidation of isoniazid at less positive
      potential. Large decrease in the overpotential and significant enhancement in the
      anodic peak current with respect to the polycrystalline Au electrode are
      observed. The nanoparticle based platform is highly sensitive (4.03+/-0.01 nA/nM)
      and it linearly responds to isoniazid up to the concentration of 1mM. It could
      detect as low as 0.1 nM (S/N=5) of isoniazid at the potential of 10 mV in aqueous
      solution without any redox mediator. The catalytic response of the sensing
      platform depends on the amount of nanoparticles loaded onto the silicate network.
      Very interestingly, the sensing platform could simultaneously detect isoniazid
      and hydrazine in their coexistence without compromising the sensitivity. Well
      separated individual voltammetric response is obtained for both analytes. The
      sensing platform is highly stable and it can be repeatedly used for 7 days.

PMID- 20152393
TI  - Preparation of silver hexacyanoferrate nanoparticles and its application for the
      simultaneous determination of ascorbic acid, dopamine and uric acid.
AB  - A silver hexacyanoferrate nanoparticles/carbon nanotubes modified glassy carbon
      electrode was fabricated and then successfully used for the simultaneous
      determination of ascorbic acid, dopamine and uric acid by cyclic voltammetry. A
      detailed investigation by transmission electron microscopy (TEM) and
      electrochemistry was performed in order to elucidate the preparation process and
      properties of the nanocomposites. The size of silver hexacyanoferrate
      nanoparticles was examined by TEM around 27 nm. Linear calibration plots were
      obtained over the range of 4.0 x 10(-6)-7.8 x 10(-5), 2.4 x 10(-6)-1.3 x 10(-4)
      and 2.0 x 10(-6)-1.5 x 10(-4) mol L(-1) with detection limits of 4.2 x 10(-7),1.4
      x 10(-7) and 6.0 x 10(-8) mol L(-1) for ascorbic acid, dopamine and uric acid,
      respectively. The practical analytical utilities of the modified electrode were
      demonstrated by the determination of ascorbic acid, dopamine and uric acid in
      urine and human blood serum samples.

PMID- 20152394
TI  - Detection of bio-constituents in complex biological tissue using Raman
      microscopy. Application to human nail clippings.
AB  - Raman spectra of human nail clippings from various sources were collected and
      then deconvoluted to obtain the pure component spectra of the underlying
      constituents present. This blind-deconvolution was performed using a self
      modeling curve resolution technique, namely band-target entropy minimization
      (BTEM). The aim was to simplify the complexity of the Raman spectra and hence to
      identify the underlying biological molecules in more detail. BTEM analysis could
      recover 13 pure component Raman spectral estimates from the collected 438 spectra
      measured from 113 nail samples. Six recovered pure component spectral estimates
      correspond to proteins or polypeptides that contain various amino acids such as
      phenylalanine, tyrosine, tryptophan, and cysteine. Two are associated with the
      secondary structures of proteins, and five are associated with two carotenoid
      species, lipid, ferulic acid, and calcium phosphate. Subsequently, the relative
      concentrations of these bio-constituents were calculated from the measured
      mixture spectra and the pure component BTEM estimates. These profiles indicated
      that the concentrations of some bio-constituents are correlated while others are
      not. A further analysis using target transformation factor analysis (TTFA)
      revealed the possible presence of curcumin in the human nails. Since the present
      approach and analysis is rather general, it might be extended to many other
      biological tissues in a rather straightforward and similar manner, thus revealing
      more detailed underlying biochemical information such as biomarkers that may be
      useful for diagnostic purposes.

PMID- 20152395
TI  - Rapid determination of aristolochic acids I and II in herbal products and
      biological samples by ultra-high-pressure liquid chromatography-tandem mass
      spectrometry.
AB  - Aristolochic acids (AAs) are a mixture of structural-related compounds, in which
      aristolochic acid I (AA I) and aristolochic acid II (AA II) are reported to be
      correlated with Aristolochic acid nephropathy (AAN). In this work, a rapid and
      sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry
      (UHPLC-MS/MS) method was developed to determine AA I and AA II in herbal products
      and biological fluids. By using gradient elution with a mobile phase composed of
      a mixture of 10mM ammonium formate buffer (pH 3.0) and acetonitrile, AAs could be
      determined within 10 min. Under optimum UHPLC-MS/MS conditions, the limit of
      detections was 0.14 and 0.26 ng mL(-1) for AA I and AA II, respectively. Run-to
      run repeatability and intermediate precision of peak area for AA I and AA II were
      less than 5.74% relative standard deviation (RSD). Accuracy was tested by spiking
      10, 100 and 1000 ng mL(-1) in rat serum and the recoveries were within 76.5
      92.9%. Matrix effects were within 78.8-127.7%. The developed method was
      successfully applied to determine AA I and AA II in several herbal products and
      to investigate their pharmacokinetic behavior in female Wister rats. The result
      shows that the developed UHPLC-MS/MS method is efficient, sensitive, and accurate
      for the determination of AA I and AA II in herbal products and biological
      samples.

PMID- 20152396
TI  - A new and facile method for measurement of apparent density of monodisperse
      polymer beads.
AB  - The apparent density, an intrinsic physical property of polymer beads, plays an
      important role in the application of beads in micro-total analysis systems and
      separation. Here we have developed a new, facile and milligram-scale method to
      describe the motion of beads in aqueous solution and further detect the apparent
      density of beads. The motion of beads in solutions is determined by the viscosity
      of solutions and the density difference between beads and solutions. In this
      study, using various glycerol aqueous solutions with certain viscosities and
      densities, the motion time (i.e. floating or sedimentation time) of hybrid
      polymer beads was experimentally measured and theoretically deduced, and
      consequently, the apparent density of monodisperse beads can be quickly and
      easily calculated. The results indicated that the present method provided a more
      precise way to predict the movement of hybrid beads in aqueous solution compared
      with the approach for commercial use. This new method can be potentially employed
      in flow cytometry, suspension stability, and particle analysis systems.

PMID- 20152397
TI  - Simultaneous determination of ascorbic acid, dopamine, uric acid and xanthine
      using a nanostructured polymer film modified electrode.
AB  - This paper describes the simultaneous determination of ascorbic acid (AA),
      dopamine (DA), uric acid (UA) and xanthine (XN) using an ultrathin
      electropolymerized film of 2-amino-1,3,4-thiadiazole (p-ATD) modified glassy
      carbon (GC) electrode in 0.20 M phosphate buffer solution (pH 5.0). Bare GC
      electrode failed to resolve the voltammetric signals of AA, DA, UA and XN in a
      mixture. On the other hand, the p-ATD modified electrode separated the
      voltammetric signals of AA, DA, UA and XN with potential differences of 110, 152
      and 392 mV between AA-DA, DA-UA and UA-XN, respectively and also enhanced their
      oxidation peak currents. The modified electrode could sense 5 microM DA and 10
      microM each UA and XN even in the presence of 200 microM AA. The oxidation
      currents were increased from 30 to 300 microM for AA, 5 to 50 microM for DA and
      10 to 100 microM for each UA and XN, and the lowest detection limit was found to
      be 2.01, 0.33, 0.19 and 0.59 microM for AA, DA, UA and XN, respectively (S/N=3).
      The practical application of the present modified electrode was demonstrated by
      the determination of AA, UA and XN in human urine samples.

PMID- 20152398
TI  - Multi-walled carbon nanotubes and Ru(bpy)3(2+)/nano-Au nano-sphere as efficient
      matrixes for a novel solid-state electrochemiluminescence sensor.
AB  - An effective method for immobilization of Ru(bpy)(3)(2+) on glassy carbon
      electrode surface (GCE) is developed for the preparation of a novel
      electrochemiluminescence sensor. First of all, the positively charged
      Ru(bpy)(3)(2+) is modified on the surface of negatively charged gold
      nanoparticles (nano-Au) via the electrostatic interactions to obtain the
      Ru(bpy)(3)(2+)/nano-Au nano-sphere (abbreviate as Ru-AuNPs). Subsequently, the
      large amount of Ru-AuNPs are immobilized on the multi-wall carbon nanotubes
      (MWCNTs)-Nafion homogeneous composite coated GCE by dual interaction: firstly,
      the Nafion, a kind of typical cation-exchange membrane, can absorb the Ru-AuNPs
      as the enrichment of cation Ru(bpy)(3)(2+) on the Ru-AuNPs surface; secondly, the
      employment of carboxylic MWCNTs in the Nafion film can also chemosorb the
      Ru(bpy)(3)(2+) cation on the Ru-AuNPs surface to increase the carrier content. At
      the same time, the experiment confirms that the enhancement of the ECL intensity
      on the sensor is attributed to following reasons. One hand, the employment of
      MWCNTs in the Nafion film enlarged the electro-active surface areas to benefit
      the contact between the signal probe on the composite film and coreactant used as
      reinforcing agent. On the other hand, the nano-materials of MWCNTs and nano-Au
      also improve the conductivity of the assembled film to increase the quantity of
      excited state of Ru(bpy)(3)(2+) in the unit time under the electrochemical
      condition and finally cause better properties in luminescence. In the experiment,
      the influence of the coreactant tripropylamine (TPA) on proposed ECL sensor is
      investigated. The logarithm of ECL intensity is proportional to the logarithm of
      TPA concentration on the range of 4 x 10(-10)M to 2.8 x 10(-6)M and 2.8 x 10(-6)M
      to 0.71 x 10(-3)M. After optimizing these conditions, the ECL sensor with TPA as
      coreactant is employed to detect a kind of alkaloid medicine, Matrine, for
      evaluating the practical application in the medicine analysis. The present sensor
      with TPA as coreactant shows the good response to the medicine concentration of
      the Matrine from 2.0 x 10(-6)M to 6.0 x 10(-3)M, which is used to detect the
      Matrine concentration in the Matrine injection.

PMID- 20152399
TI  - Variable-weighted least-squares support vector machine for multivariate spectral
      analysis.
AB  - Multivariate spectral analysis has been widely applied in chemistry and other
      fields. Spectral data consisting of measurements at hundreds and even thousands
      of analytical channels can now be obtained in a few seconds. It is widely
      accepted that before a multivariate regression model is built, a well-performed
      variable selection can be helpful to improve the predictive ability of the model.
      In this paper, the concept of traditional wavelength variable selection has been
      extended and the idea of variable weighting is incorporated into least-squares
      support vector machine (LS-SVM). A recently proposed global optimization method,
      particle swarm optimization (PSO) algorithm is used to search for the weights of
      variables and the hyper-parameters involved in LS-SVM optimizing the training of
      a calibration set and the prediction of an independent validation set. All the
      computation process of this method is automatic. Two real data sets are
      investigated and the results are compared those of PLS, uninformative variable
      elimination-PLS (UVE-PLS) and LS-SVM models to demonstrate the advantages of the
      proposed method.

PMID- 20152400
TI  - Simultaneous determination of angiotensins II and 1-7 by capillary zone
      electrophoresis in plasma and urine from hypertensive rats.
AB  - We describe the procedure developed for the simultaneous detection and
      quantification of angiotensin II and angiotensin-(1-7), by capillary zone
      electrophoresis with UV detection by photodiode-array, at a wavelength of 200 nm,
      in the plasma and urine from hypertensive rats. Optimal separation was achieved
      with a 100mM boric acid+3mM tartaric acid+10 fM gold (III) chloride electrolyte
      solution at pH 9.80. The applied voltage was 30 kV and the capillary temperature
      was kept constant at 20 degrees C. The method was over the concentration range of
      0.01-500 pmol/mL. All determination coefficients were higher or equal to 0.9985.
      Limits of detection and quantification for angiotensin II were 0.0110 pmol/mL
      (S/N=3) and 0.0195 pmol/mL (S/N=5), respectively. While for angiotensin-(1-7),
      the limits were 0.0112 pmol/mL (S/N=3) and 0.0193 pmol/mL (S/N=5), respectively.
      The present method offers a time-saving way to simultaneous determination of
      angiotensin II and angiotensin-(1-7), since it can be completed in 10 min,
      compared to other methodologies reported in the literature for capillary
      electrophoresis and liquid chromatography, which require more than 1h for
      analysis of complex matrices, such as plasma and urine. The procedure is
      illustrated by experiments that quantify simultaneously angiotensin II and
      angiotensin-(1-7) in plasma and urine from hypertensive and normotensive rats,
      with and without antihypertensive treatment. The levels of angiotensin II and
      angiotensin-(1-7) detected in the experimental model, resulted in a recovery of
      99.00-106.01% and a reproducibility of less than 10%. The proposed analytical
      method is a use full tool for the simultaneous detection of angiotensin II and
      angiotensin-(1-7) implicated in vascular remodeling in pathologies such as
      hypertension.

PMID- 20152401
TI  - Monodispersed, molecularly imprinted polymers for cinchonidine by precipitation
      polymerization.
AB  - Three monodispersed, molecularly imprinted polymers (MIPs) for cinchonidine (CD)
      have been synthesized by precipitation polymerization. MIP1 was prepared using
      methacrylic acid (MAA) as a functional monomer and divinylbenzene (DVB) as a
      cross-linker and MIP2 was prepared with further addition of 2-hydroxyethyl
      methacrylate (HEMA) as a co-monomer. For the preparation of MIP3, core-shell type
      MIP, monodispersed DVB homopolymers, which are prepared by precipitation
      polymerization, were used as a core and CD-imprinted MAA-DVB copolymer phases
      were coated onto the core. Three MIPs synthesized gave monodispersed, spherical
      beads in micrometer sizes. The binding characteristics and molecular recognition
      properties of MIP1-3 were examined by Scatchard analysis and chromatographic
      studies. The association constant of CD with MIP1 was the highest among MIPs
      prepared, while that with MIP3 was the lowest. The template molecule, CD, was
      more retained than its stereoisomer, cinchonine, on the three MIPs, and the
      stereoseparation factor of 38 was obtained with MIP3.

PMID- 20152402
TI  - Polymerized ionic liquid-wrapped carbon nanotubes: the promising composites for
      direct electrochemistry and biosensing of redox protein.
AB  - Polymerized ionic liquid-wrapped carbon nanotubes (PIL-CNTs) were firstly
      designed for direct electrochemistry and biosensing of redox proteins. The CNTs
      were coated successfully with polymerized ionic liquid (PIL) layer, as verified
      by transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and
      Fourier transform infrared (FT-IR) spectroscopy. The PIL-CNTs were dispersed
      better in water and showed superior electrocatalysis toward O(2) and H(2)O(2)
      comparing to pristine CNTs and the mixture of IL monomer and CNTs. With glucose
      oxidase (GOD) as a protein model, the direct electrochemistry of the redox
      protein was investigated on the PIL-CNTs modified glassy carbon (GC) electrode
      and excellent direct electrochemical performance of GOD molecules was observed.
      The proposed biosensor (GOD/PIL-CNTs/GC electrode) displayed good analytical
      performance for glucose with linear response up to 6mM, response sensitivity of
      0.853 microA mM(-1), good stability and selectivity.

PMID- 20152403
TI  - Direct fluorescence detection of point mutations in human genomic DNA using
      microbead-based ligase chain reaction.
AB  - This report has described a convenient genotyping method capable of detecting
      point mutations directly in human genomic DNA based on the combination of ligase
      chain reaction (LCR) and microbead-enrichment technique. LCR primers, including a
      biotin-labeled common primer and two fluorescence-labeled allele-specific
      primers, are designed for two alleles of a mutated site. When genomic DNA carries
      the mutated site, the common primer and allele-specific primer are ligated to
      form exponential amplified biotin-labeled fluorescence ligation products. These
      ligated products are enriched by streptavidin-coated microbeads, and genotypes
      are identified conveniently according to the fluorescence color of microbeads
      using fluorescent microscopy. Due to amplification of LCR process and enrichment
      of microbeads, the detection limit of the proposed method is as low as 10(
      15)mol/L templates. The method provides a convenient and simple strategy to
      detect point mutation directly in human genome. We have confirmed the efficiency
      of this approach with the identification of beta-globin gene point mutation,
      which results in the reduced production of globin in an inherited hemoglobin
      disorder thalassemia disease.

PMID- 20152404
TI  - Square wave voltammetric determination of nitrofurantoin in pharmaceutical
      formulations on highly boron-doped diamond electrodes at different boron-doping
      contents.
AB  - The influence of the boron-doping levels in boron-doped diamond film electrodes
      on the electrochemical response of nitrofurantoin (NFT) and the development of an
      electroanalytical procedure for NFT determination were investigated. The
      investigations were carried out using the techniques of cyclic voltammetry and
      square wave voltammetry on diamond film electrodes with different boron-doping
      levels (i.e., 5000, 10,000 and 20,000 mg L(-1)). The level of boron-doping in the
      diamond film electrodes influenced the electrochemical reduction of NFT. The
      appropriate cyclic voltammetric response of NFT was obtained with Britton
      Robinson buffer at pH 4 and for diamond films doped with 10,000 and 20,000 mg L(
      1) of boron. These two films were selected for the development of the
      electroanalytical procedure. The use of square wave voltammetry with the
      optimized parameters demonstrated a good linear relationship between the peak
      current and the NFT concentration for a wide range of concentration. The lower
      limit of detection for the electrodes doped with 10,000 and 20,000 mg L(-1) of
      boron were 2.69 x 10(-8) mol L(-1) (6.40 microg L(-1)) and 8.15 x 10(-9) mol L(
      1) (1.94 microg L(-1)), respectively, while the lower limits of quantification
      were 8.96 x 10(-8) mol L(-1) (21.33 microg L(-1)) and 2.72 x 10(-8) mol L(-1)
      (6.47 microg L(-1)), respectively. The applicability of the proposed procedure
      was tested using a commercial pharmaceutical formulation of NFT, and the results
      were compared with the procedure recommended by the British Pharmacopeia. The
      proposed procedure was sensitive, accurate and precise for analysis of NFT and
      did not require complex preparations or renovations of the electrode surface.
      This presents the advantage of eliminating mercury waste and minimizing the
      adsorptive problems related to the use of other electrodic solid surfaces.

PMID- 20152405
TI  - Electrochemiluminescence of CdTe quantum dots as labels at nanoporous gold leaf
      electrodes for ultrasensitive DNA analysis.
AB  - A new electrochemiluminescence (ECL) DNA assay is developed using quantum dots
      (QDs) as DNA labels. When nanoporous gold leaf (NPGL) electrodes are used,
      sensitivity of the ECL assay is remarkably increased due to ultra-thin nanopores.
      In this assay, target DNA (t-DNA) is hybridized with capture DNA (c-DNA) bound on
      the NPGL electrode, which is fabricated by conjugating amino-modified c-DNA to
      thioglycolic acid (TGA) modified at the activated NPGL electrode. Following that,
      amino-modified probe DNA is hybridized with the t-DNA, yielding sandwich hybrids
      on the NPGL electrode. Then, mercaptopropionic acid-capped CdTe QDs are labeled
      to the amino group end of the sandwich hybrids. Finally, in the presence of
      S(2)O(8)(2-) as coreactant, ECL emission of the QD-labeled DNA hybrids on the
      NPGL electrode is measured by scanning the potential from 0 to -2V to record the
      curve of ECL intensity versus potential. The maximum ECL intensity (I(m,ECL)) on
      the curve is proportional to t-DNA concentration with a linear range of 5 x 10(
      15) to 1 x 10(-11)mol/L. The ECL DNA assay can be used to determine DNA
      corresponding to mRNA in cell extracts in this study.

PMID- 20152406
TI  - Determination of rare-earth elements in uranium-bearing materials by inductively
      coupled plasma mass spectrometry.
AB  - A novel and simple analytical procedure has been developed for the trace-level
      determination of lanthanides (rare-earth elements) in uranium-bearing materials
      by inductively coupled plasma sector-field mass spectrometry (ICP-SFMS). The
      method involves a selective extraction chromatographic separation of lanthanides
      using TRU resin followed by ICP-SFMS analysis. The limits of detection of the
      method proposed is in the low pg g(-1) range, which are approximately two orders
      of magnitude better than that of without chemical separation. The method was
      validated by the measurement of reference material and applied for the analysis
      of uranium ore concentrates (yellow cakes) for nuclear forensic purposes, as a
      potential application of the methodology.

PMID- 20152407
TI  - Active content determination of non-coated pharmaceutical pellets by near
      infrared spectroscopy: method development, validation and reliability evaluation.
AB  - A robust near infrared (NIR) method able to quantify the active content of pilot
      non-coated pharmaceutical pellets was developed. A protocol of calibration was
      followed, involving 2 operators, independent pilot batches of non-coated
      pharmaceutical pellets and two different NIR acquisition temperatures. Prediction
      models based on Partial Least Squares (PLS) regression were then carried out.
      Afterwards, the NIR method was fully validated for an active content ranging from
      80 to 120% of the usual active content using new independent pilot batches to
      evaluate the adequacy of the method to its final purpose. Conventional criteria
      such as the R(2), the Root Mean Square Error of Calibration (RMSEC), the Root
      Mean Square Error of Prediction (RMSEP) and the number of PLS factors enabled the
      selection of models with good predictive potential. However, such criteria
      sometimes fail to choose the most fitted for purpose model. Therefore, a novel
      approach based on accuracy profiles of the validation results was used, providing
      a visual representation of the actual and future performances of the models.
      Following this approach, the prediction model using signal pre-treatment
      Multiplicative Scatter Correction (MSC) was chosen as it showed the best ability
      to quantify accurately the active content over the 80-120% active content range.
      The reliability of the NIR method was tested with new pilot batches of non-coated
      pharmaceutical pellets containing 90 and 110% of the usual active content, with
      blends of validation batches and industrial batches. All those batches were also
      analyzed by the HPLC reference method and relative errors were calculated: the
      results showed low relative errors in full accordance with the results obtained
      during the validation of the method, indicating the reliability of the NIR method
      and its interchangeability with the HPLC reference method.

PMID- 20152408
TI  - Whole-cell spectroscopy is a convenient tool to assist molecular identification
      of cultivatable marine bacteria and to investigate their adaptive metabolism.
AB  - Recent developments in whole-cell spectroscopic methods allow rapid
      characterization of microorganisms of interest to human health, but have yet to
      be widely applied to marine microbiological studies. In this study of bacteria
      associated with the kelp Laminaria digitata, we have isolated 18 epiphytic
      bacterial strains from several thalli, sequenced their 16S rDNA, built
      corresponding phylogenetic trees, and characterized them using spectroscopic
      methods. Molecular taxonomy revealed Gram(+)Actinobacteria and Gram(
      )Alphaproteobacteria, Gammaproteobacteria and Bacteroidetes. Twelve marine
      reference strains (Gram(+)Firmicutes, and Gram(-)Alphaproteobacteria,
      Gammaproteobacteria and Bacteroidetes) were treated accordingly. Whole-cell MALDI
      TOF MS spectral profiles of 29 of the 30 strains were built into a database
      against which 16 replicate spectra of each strain were compared and categorized
      into groups. The proton HR-MAS NMR stack plots allowed visual delineation into
      taxonomic groups according to their most common peaks, in agreement with
      identifiable compounds from corresponding D(2)O solution spectra. With both
      methods, these groups corresponded to taxa identified by 16S rDNA sequences,
      MALDI-TOF MS being more discriminative than HR-MAS NMR. Culture age did not
      influence the spectral signatures in both approaches. Most cells grown under
      minimal conditions (VNSS medium) afforded HR-MAS NMR profiles markedly different
      to those grown in enriched conditions (ZoBell medium), indicating different
      adaptive metabolic responses between the two media. Spectral signatures obtained
      under strictly controlled conditions can be used as rapid and reliable tools for
      taxonomic purposes and as markers of physiological status.

PMID- 20152409
TI  - Application of point-to-point matching algorithms for background correction in on
      line liquid chromatography-Fourier transform infrared spectrometry (LC-FTIR).
AB  - A new background correction method for the on-line coupling of gradient liquid
      chromatography and Fourier transform infrared spectrometry has been developed. It
      is based on the use of a point-to-point matching algorithm that compares the
      absorption spectra of the sample data set with those of a previously recorded
      reference data set in order to select an appropriate reference spectrum. The
      spectral range used for the point-to-point comparison is selected with minimal
      user-interaction, thus facilitating considerably the application of the whole
      method. The background correction method has been successfully tested on a
      chromatographic separation of four nitrophenols running acetonitrile (0.08%, v/v
      TFA):water (0.08%, v/v TFA) gradients with compositions ranging from 35 to 85%
      (v/v) acetonitrile, giving accurate results for both, baseline resolved and
      overlapped peaks.

PMID- 20152410
TI  - Contribution to vapor generation-inductively coupled plasma spectrometric
      techniques for determination of sulfide in water samples.
AB  - Vapor generation-inductively coupled plasma-optical emission spectrometry was
      used for the determination of sulfide in water samples preserved by the addition
      of a zinc acetate and sodium hydroxide solution. Hydrogen sulfide and acid
      volatile sulfides were transformed, by acidification, to a gaseous phase in a
      vapor generator and subsequently detected by inductively coupled plasma optical
      emission spectrometry. Compounds interfering with iodometric titration and
      spectrophotometric determination were examined as potential chemical
      interferents. The proposed method provides results comparable to iodometric
      titration in the tested concentration range 0.06-22.0 mg L(-1). Limit of
      detection for the determination of hydrogen sulfide by this method is 0.03 mg L(
      1).

PMID- 20152411
TI  - Molecularly imprinted polymer for the extraction of parabens from environmental
      solid samples prior to their determination by high performance liquid
      chromatography-ultraviolet detection.
AB  - An analytical methodology incorporating a molecularly imprinted solid-phase
      extraction procedure (MISPE) has been developed for the determination of parabens
      in environmental solid samples. Four different polymers were prepared combining
      the use of acetonitrile or toluene as porogen, and 4-vinylpyridine (VP) or
      methacrylic acid (MAA) as monomer, using benzylparaben (BzP) as a template
      molecule. Although all the polymers were able to recognize the template in
      rebinding experiments, the MIP prepared in toluene using MAA showed better
      performance. This polymer was also capable of recognizing other parabens (methyl,
      ethyl, isopropyl, propyl, isobutyl, butyl and benzylparaben) allowing to develop
      an appropriated MISPE procedure for this family of compounds. The extraction of
      the parabens from environmental solid samples was performed by ultrasonic
      assisted extraction in small columns (SAESC), and this procedure next to MISPE as
      clean-up step followed by HPLC-UV determination was successfully used for the
      determination of parabens in soil and sediment samples of different locations.
      Recoveries ranging from 80% to 90% have been achieved depending on the compound
      and the samples, and limits of detection (LODs) were under 1 ng g(-1) for all the
      compounds, making this method suitable for the determination of parabens in
      environmental solid matrices. The method was further applied to the determination
      of paraben contents in real samples, founding levels up to 11.5 ng g(-1) in sea
      sediments.

PMID- 20152412
TI  - A Wireless Sensor Network approach for distributed in-line chemical analysis of
      water.
AB  - In this work we propose the implementation of a distributed system based on a
      Wireless Sensor Network for the control of a chemical analysis system for fresh
      water. This implementation is presented by describing the nodes that form the
      distributed system, the communication system by wireless networks, control
      strategies, and so on. Nitrate, ammonium, and chloride are measured in-line using
      appropriate ion selective electrodes (ISEs), the results obtained being compared
      with those provided by the corresponding reference methods. Recovery analyses
      with ISEs and standard methods, study of interferences, and evaluation of major
      sensor features have also been carried out. The communication among the nodes
      that form the distributed system is implemented by means of the utilization of
      proprietary wireless networks, and secondary data transmission services (GSM or
      GPRS) provided by a mobile telephone operator. The information is processed,
      integrated and stored in a control center. These data can be retrieved--through
      the Internet--so as to know the real-time system status and its evolution.

PMID- 20152413
TI  - Development and validation of a cellular biosensor detecting pesticide residues
      in tomatoes.
AB  - Two of the most important categories of pesticides used in agricultural practice
      are organophosphates and dithiocarbamates. Their extensive and inappropriate use
      has rendered their reliable monitoring at trace levels more and more necessary.
      This study presents the construction of a rapid and sensitive cellular biosensor
      test based on the measurement of changes of the cell membrane potential of
      immobilized cells, according to the working principle of the Bioelectric
      Recognition Assay (BERA). The cells were immobilized by entrapment in a sodium
      alginate bead and directly applied in different pesticide dilutions and
      agricultural samples. The pesticides used were the organophosphate insecticide
      diazinon and the dithiocarbamate fungicide propineb. Two different cell types,
      N2a (neuroblastoma) and Vero (fibroblast) were used as the biosensory elements in
      order to investigate their differential response against the pesticides. In this
      way, we hoped to increase the selectivity of the assay. Based on the observed
      patterns of response, we demonstrate that the sensor can be used for the
      qualitative and, in some concentrations, quantitative detection of the pesticides
      with a high degree of reproducibility. The lowest detected concentration was 3nM.
      Finally, for the investigation of the effects of different pesticides on the
      accumulation of cytosolic Ca(2+), we conducted a fluorescent assay on N2a cells
      treated with tomato sample extracts, which were replicates of the E.U.
      proficiency test sample. The tomato samples were either organically grown or
      contained 14 different pesticides. The experimental results showed a higher
      increase of the intracellular Ca(2+) concentration in cells treated with non
      organic samples compared to the cells treated with organic samples.

PMID- 20152414
TI  - Sonogel-carbon electrode based on hemin for detection of superoxide.
AB  - The Sonogel electrode was immersed in hemin solution to obtain the hemin-Sonogel
      modified electrode by cyclic voltammetry (CV). It was applied to detect
      superoxide radicals produced by xanthine oxidase catalyzed hypoxanthine
      oxidation. The characterization of hemin-Sonogel was modified by impedance and
      CV.

PMID- 20152415
TI  - A sensor based on electrodes supported on ion-exchange membranes for the flow
      injection monitoring of sulphur dioxide in wines and grape juices.
AB  - A sensitive and fast responding electrochemical sensor is described for the
      determination of free and total sulphur dioxide in wines and grape juices which
      prevents interferences coming from ethanol and other natural components. It
      consists of a cell provided with a porous gold working electrode supported on one
      face of an ion-exchange membrane, acting as a solid polymer electrolyte (SPE),
      which allows gaseous electroactive analytes to be detected. This sensor was used
      as an amperometric detector for a flow injection system in which controlled
      volumes of headspace equilibrated with samples were injected. This approach was
      adopted to make also possible the determination of total SO(2), avoiding
      drawbacks caused by the high relative humidity generated by the sample heating
      resulting from the neutralization reaction of excess NaOH, whose addition was
      required to release sulphur dioxide from its combined forms. Factors affecting
      the detection process were examined and optimised. Under the identified optimal
      conditions, SO(2) detection resulted in sharp peaks which allowed to infer
      detection limits for a signal-to-noise ratio of 3, referred to liquid samples, of
      0.04 and 0.02 mg L(-1) for free and total SO(2) which were determined at 20 and
      35 degrees C, respectively. Moreover, the responses were found to be
      characterized by good repeatability (+/-2% and +/-4%, respectively) and linear
      dependence on the SO(2) concentration over a wide range (0.2-500 mg L(-1) for
      both free and total SO(2)). Finally, the long-term stability of the sensor turned
      out to be totally satisfactory in that responses changed of +/-9% alone even
      after long periods of continuous use. The application to some commercial wines
      and grape juices is also presented.

PMID- 20152416
TI  - Headspace single-drop microextraction and fibre optics-based cuvetteless micro
      spectrophotometry for the determination of chloride involving oxidation with
      permanganate.
AB  - Headspace single-drop microextraction has been investigated for the determination
      of chloride in conjunction with fibre optic-based cuvetteless micro
      spectrophotometry which accommodates sample volume of 1 microL placed between the
      two ends of optical fibres. Method has been evolved for the determination of
      0.025-4 mg L(-1) of chloride involving its oxidation with permanganate in
      sulphuric acid medium, and reaction of chlorine with 2 microL drop of starch
      iodide reagent suspended at the tip of microsyringe needle in the headspace of
      the reaction mixture. The limit of detection was found to be 2.8 microg L(-1) of
      chloride which was better than obtained by existing methods. The method was
      highly selective and a number of ions which interfered severely in other methods
      did not affect the results. The method has been used to analyze water samples,
      inorganic compounds and cement when the overall recovery of chloride was 94.9%
      with a relative standard deviation of 3.9%.

PMID- 20152417
TI  - A simplified UV spectrometric method for determination of peroxide value in
      thermally oxidized canola oil.
AB  - The aim of present study was to develop a simple method on UV spectrometer for
      the determination of peroxide value (PV) of the frying oil. The basis of the PV
      determination was the stoichiometric reaction of triphenylphosphine (TPP) with
      the hydroperoxides present in frying oil to produce triphenylphosphine oxide
      (TPPO), which exhibits a readily measurable absorption band at 240 nm by
      ultraviolet region. The PV ranged between 0.15 and 11.66 meq. of active oxygen
      per kilogram of oil as the canola oil was heated from 0 to 12h in the fryer at
      180 degrees C. The proposed method was correlated with official AOCS titration
      method and best correlation coefficient (R(2)=0.99525) was achieved, proving that
      there is no significant difference in the results. Therefore, developed method
      could serve as an alternative to the titration method, for the determination of
      PV in frying oils.

PMID- 20152418
TI  - Preparation of a carbon ceramic electrode modified by 4-(2-pyridylazo)-resorcinol
      for determination of trace amounts of silver.
AB  - A 4-(2-pyridylazo)-resorcinol (PAR)-modified carbon ceramic electrode (CCE)
      prepared by the sol-gel technique has been reported for the first time in this
      paper. By immersing the CCE in aqueous solution of PAR (0.001molL(-1)), after a
      short period of time, a thin film of PAR was rapidly formed on the surface of the
      electrode due to its strong adsorption properties. A differential pulse anodic
      stripping voltammetric (DPASV) method was developed for determination of Ag(I) at
      the modified carbon ceramic electrode. The analysis procedure consisted of an
      open circuit accumulation step in a sample solution which was continuously
      stirred for 12 min. This was followed by replacing the medium with a clean
      solution where the accumulated Ag(I) was reduced for 15s in -0.6 V. Then, the
      potential was scanned from -0.2 to +0.2V to obtain the voltammetric peak. The
      detection limit of silver(I) was 0.123 microg L(-1), and for seven successive
      determinations of 10, 100 and 200 microg L(-1) Ag(I), the relative standard
      deviations were 2.1, 1.4 and 1.03%, respectively. The calibration curve was
      linear for 0.5-300 microg L(-1) silver(I). The procedure was applied to determine
      silver(I) in X-ray photographic films and super-alloy samples.

PMID- 20152419
TI  - Chemometrical strategies for feature selection and data compression applied to
      NIR and MIR spectra of extra virgin olive oils for cultivar identification.
AB  - The possibility provided by Chemometrics to extract and combine (fusion)
      information contained in NIR and MIR spectra in order to discriminate
      monovarietal extra virgin olive oils according to olive cultivar (Casaliva,
      Leccino, Frantoio) has been investigated. Linear discriminant analysis (LDA) was
      applied as a classification technique on these multivariate and non-specific
      spectral data both separately and jointly (NIR and MIR data together). In order
      to ensure a more appropriate ratio between the number of objects (samples) and
      number of variables (absorbance at different wavenumbers), LDA was preceded
      either by feature selection or variable compression. For feature selection, the
      SELECT algorithm was used while a wavelet transform was applied for data
      compression. Correct classification rates obtained by cross-validation varied
      between 60% and 90% depending on the followed procedure. Most accurate results
      were obtained using the fused NIR and MIR data, with either feature selection or
      data compression. Chemometrical strategies applied to fused NIR and MIR spectra
      represent an effective method for classification of extra virgin olive oils on
      the basis of the olive cultivar.

PMID- 20152420
TI  - 11-Molybdobismuthophosphate--a new reagent for the determination of ascorbic acid
      in batch and sequential injection systems.
AB  - The guanidinium salt of the new heteropolymolybdate 11-molybdobismuthophosphate
      Gua(6)PBiMo(11)O(40) (11-MBP) was synthesized, characterized and used as a
      reagent for batch spectrophotometric (SP) and sequential injection determination
      of ascorbic acid (AsA). When compared to other Keggin's heteropolyanions, the
      reduction of 11-MBP with AsA is both fast and maximal within a pH range of 1.6
      2.0. The stoichiometry of the reaction was determined using molar ratio and
      continuous variation methods and was shown to be 1:1. The molar absorptivity of
      the reduced form of 11-MBP was 6.0 x 10(3)L mol(-1)cm(-1) at 720 nm. The reaction
      is also specific for AsA. Only cysteine, hydroquinone and hydroxyacids were found
      to interfere with the reaction, while no interference was observed with the
      common reducing agents, including reducing sugars, catecholamines, nitrite,
      sulfite and iron(II) ions. Batch SP and sequential injection analysis (SIA)
      systems were developed for the determination of AsA, with calibration ranges of
      the SP methods at 2x10(-6)-8 x 10(-5)M for a 10mm cell and 5 x 10(-7)-3 x 10(-5)M
      for a 50mm cell and a limit of detection at 3 x 10(-7)M. The linear range of the
      SIA method was 6 x 10(-6)-5 x 10(-4)M, with a detection limit of 2 x 10(-6)M and
      a sample throughput of 15 h(-1). The proposed methods were successfully used for
      the determination of AsA in both pharmaceuticals and fruit juices, and the
      results were consistent with those provided by the 2,6-dichlorophenolindophenol
      method.

PMID- 20152421
TI  - Determination of NTBC in serum samples from patients with hereditary tyrosinemia
      type I by capillary electrophoresis.
AB  - Hereditary tyrosinemia type I is a serious metabolic disorder leading to liver
      failure. 2-(2-Nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) is a
      relatively new drug which is used to prevent the accumulation of toxic
      metabolites in patients with hereditary tyrosinemia type I. In the present study,
      we have developed a new, simple, fast, and cost-effective capillary
      electrophoresis method for the quantitative monitoring of this drug in serum
      samples. Micellar electrochromatographic separation of NTBC was performed using
      20 mmol/L phosphate and 40 mmol/L sodium dodecylsulfate (SDS) at pH 12 as running
      electrolyte. Separation of NTBC was achieved in around 4 min. Reproducibilities
      of migration times and corrected peak areas of NTBC (as R.S.D.%) were found as
      0.73 and 1.99, respectively. The detection limit was 3.17 and the quantification
      limit was 10.6 micromol/L for NTBC using UV detection at 278 nm. The utility of
      the method was demonstrated by the detection of NTBC in serum samples from
      patients with hereditary tyrosinemia type I using this drug.

PMID- 20152422
TI  - Separation of PCBs by liquid chromatography on reversed phase sub-2-micron
      particle columns.
AB  - A new ultra high-performance liquid chromatography method with UV detection was
      examined for detection and separation of polychlorinated biphenyls. This included
      optimization of separation conditions for two model mixtures containing seven and
      fifteen most relevant congeners, comparison of three types of reversed phase sub
      2-micron particle sized columns and assessment of system suitability under the
      optimized conditions. Calibration curves determined in the range from 0.5 to 50.0
      microg/mL exhibited correlation coefficients ranging from 0.997 to 0.999. Lower
      limits of detection ranged from 0.1 to 0.5 ppm. The most efficient Grace C18
      column filled with 1.5 microm particles was then tested to separate the complex
      commercial mixture Delor 103, where the elution order was confirmed by GC-MS. 13
      individual congeners were separated and some of the other co-eluting congeners
      could be resolved using another separation dimension performed with a mass
      spectrometry detector. The developed method could be directly applied to the
      separation of less complex mixtures in aqueous sample matrixes, which are used in
      general for enzyme degradation studies.

PMID- 20152423
TI  - Determination of dimethylselenide and dimethyldiselenide in milk and milk by
      products by solid-phase microextraction and gas chromatography with atomic
      emission detection.
AB  - A method based on solid-phase microextraction (SPME) followed by gas
      chromatography with microwave-induced plasma atomic emission detection for
      determining dimethylselenide (DMSe) and dimethyldiselenide (DMDSe) in milk and
      milk by-products is proposed. Parameters affecting the SPME, such as sample
      volume or mass, ionic strength, adsorption and desorption times and temperatures
      were optimized in the headspace mode. The matrix effect was evaluated for the
      different samples studied, concluding that standard additions calibration was
      required for quantification purposes. The detection limits ranged from 70 to 110
      pg mL(-1) for DMSe and from 80 to 400 pg mL(-1) for DMDSe, depending on the
      sample under analysis. None of the twenty-three samples analyzed contained the
      studied compounds at concentrations above the corresponding detection limits.

PMID- 20152424
TI  - Tungsten carbide precursors as an example for influence of a binder on the
      particle formation in the nanosecond laser ablation of powdered materials.
AB  - A study of LA-ICP-MS analysis of pressed powdered tungsten carbide precursors was
      performed to show the advantages and problems of nanosecond laser ablation of
      matrix-unified samples. Five samples with different compositions were pressed
      into pellets both with silver powder as a binder serving to keep the matrix
      unified, and without any binder. The laser ablation was performed by nanosecond
      Nd:YAG laser working at 213 nm. The particle formation during ablation of both
      sets of pellets was studied using an optical aerosol spectrometer allowing the
      measurement of particle concentration in two size ranges (10-250 nm and 0.25-17
      microm) and particle size distribution in the range of 0.25-17 microm.
      Additionally, the structure of the laser-generated particles was studied after
      their collection on a filter using a scanning electron microscope (SEM) and the
      particle chemical composition was determined by an energy dispersive X-ray
      spectroscope (EDS). The matrix effect was proved to be reduced using the same
      silver powdered binder for pellet preparation in the case of the laser ablation
      of powdered materials. The LA-ICP-MS signal dependence on the element content
      present in the material showed an improved correlation for Co, Ti, Ta and Nb of
      the matrix-unified samples compared to the non-matrix-unified pellets. In the
      case of W, the ICP-MS signal of matrix-unified pellets was influenced by the
      changes in the particle formation.

PMID- 20152425
TI  - An aptamer-based assay for thrombin via structure switch based on gold
      nanoparticles and magnetic nanoparticles.
AB  - An aptamer-based assay for thrombin with high specificity and sensitivity was
      presented. In the protocol, the aptamer for thrombin was immobilized on magnetic
      nanoparticle, and its complementary oligonucleotide was labeled with gold
      nanoparticles, then the aptamer was hybridized with the complementary
      oligonucleotide to form the duplex structure as a probe, this probe could be used
      for the specific recognition for thrombin. In the presence of thrombin, the
      aptamer prefer to form the G-quarter structure with thrombin, resulting in the
      dissociation of the duplex of the probe and the release of the gold labeled
      oligonucleotide. Upon this, we were able to detect thrombin through the detection
      of the electrochemical signal of gold nanoparticles. The strategy combines with
      the high specificity of aptamer and the excellent characteristics of
      nanoparticles. This assay is simple, rapid, sensitive and highly specific, it
      does not require labeling of thrombin, and it could be applied to detect thrombin
      in complex real sample. The method shows great potential in other protein
      analysis and in disease diagnosis.

PMID- 20152426
TI  - Mixed hemimicelles SPE based on CTAB-coated Fe3O4/SiO2 NPs for the determination
      of herbal bioactive constituents from biological samples.
AB  - In this paper, a solid-phase extraction (SPE) method based on mixed hemimicelles
      of cetyltrimethyl ammonium bromide (CTAB) on silica-coated magnetic nanoparticles
      (MNPs) is developed for extraction and preconcentration of compounds from the
      biological samples. We selected rhein and emodin which are the major active
      anthraquinones of rhubarb as model analytes. A high performance liquid
      chromatography-fluorescence detection (HPLC/FLD) method was developed for the
      determination of rhein and emodin in urine and serum samples. The main factors
      influencing the extraction efficiency including the amount of surfactant, the
      concentration of MNPs, the shaking time and the desorption ability of organic
      solvents were investigated and optimized. No interferences were caused by
      proteins or endogenous compounds in urine and serum samples. Good linearities
      (r(2)>0.9995) for all calibration curves were obtained, and the limits of
      detection (LODs) for rhein and emodin were 0.2 and 0.5 ng/mL in urine samples and
      7 and 10 ng/mL in serum samples, respectively. Satisfactory recoveries (92.76
      109.90% and 97.53-107.72% for rhein and emodin) in the biological matrices were
      achieved.

PMID- 20152427
TI  - Evaluation of thin mercury film rotating disk electrode to perform absence of
      gradients and Nernstian equilibrium stripping (AGNES) measurements.
AB  - In the present work, the applicability of thin mercury film on a rotating disk
      electrode (TMF-RDE), to assess the free metal ion concentration by the absence of
      gradients and Nernstian equilibrium stripping (AGNES), is evaluated. The
      thickness of the mercury film and several AGNES parameters has been optimized. A
      nominal 16 nm film is chosen due to the higher signal (faradaic current) relative
      to the value of the noise (capacitive current). Due to the smaller volume to area
      ratio, the deposition time needed to reach a certain preconcentration factor (Y)
      is much shorter than in larger electrodes, like the HMDE. The limit of detection
      (3 sigma) for lead(II) is 7.4 x 10(-9)M and 7.2 x 10(-8)M for a Y of 5000
      (deposition time of 150 s) and 1000 (deposition time of 100 s), respectively. A
      specific mathematical treatment is developed in order to subtract a corrected
      blank taking into account the degradation of the thin film (presumably, falling
      down of drops). The couple TMF-RDE/AGNES is successfully applied for speciation
      purposes in the systems Pb(II)-latex nanospheres and Pb(II)-IDA (iminodiacetic
      acid), where the stability constants calculated for both systems agree with
      values reported in the literature.

PMID- 20152428
TI  - Improving detection limits for organotin compounds in several matrix water
      samples by derivatization-headspace-solid-phase microextraction and GC-MS.
AB  - Triethyltin, tributyltin, diphenyltin and triphenyltin were selected as model
      compounds. The method is based on in situ ethylation and simultaneous headspace
      solid-phase microextraction (HS-SPME) and gas chromatographic-mass spectrometry
      analysis (GC-MS). The extraction procedure was optimized studying some variables
      such as reaction time, salinity, sample volume and headspace volume. SPME-GC-MS
      and SPME-GC-FID techniques were compared; quality assurance parameters such as
      sensitivity, selectivity and precision were established. The proposed procedure
      showed limits of detection between 0.025 and 1ng/L. The linearity was in the
      0.025-5000 ng/L range. The precision expressed as relative standard deviations
      (RSD), were below 20%. Real wastewaters and seawaters were analyzed. The method
      permits controlling legislated annual average values.

PMID- 20152429
TI  - Sample cleanup-free determination of mycophenolic acid and its glucuronide in
      serum and plasma using the novel technology of ultra-performance liquid
      chromatography-electrospray ionization tandem mass spectrometry.
AB  - Mycophenolic acid (MPA) is an immunosuppressant drug which powerfully inhibits
      lymphocyte proliferation. Since the early 1990s it has been used to prevent
      rejection in organ transplantation. The requirement of therapeutic drug
      monitoring shown in previous studies raises the necessity of acquiring accurate
      and sensitive methods to measure MPA and its major metabolite mycophenolic acid
      glucuronide (MPAG). The authors developed a sample cleanup-free, rapid, and
      highly specific method for simultaneous measurement of MPA and MPAG in human
      plasma and serum using the novel technology of ultra-performance liquid
      chromatography-electrospray ionization tandem mass spectrometry. MPA- and MPAG
      determinations were performed during a 2.0-min run time. Multiple calibration
      curves for the analysis of MPA and MPAG exhibited consistent linearity and
      reproducibility in the range of 0.05-100 (r>0.999) mg L(-1) and 4-4000 mg L(-1)
      (r>0.999), respectively. Limits of Detection were 0.014 mg L(-1) for MPA and 1.85
      mg L(-1) for MPAG. Lower Limits of Quantification were 0.05 mg L(-1) for MPA and
      2.30 mg L(-1) for MPAG. Interassay imprecision was <10% for both substances. Mean
      recovery was 103.6% (range 78.1-129.7%) for MPA and 111.1% (range 73.0-139.6%)
      for MPAG. Agreement was good for MPA and MPAG between the presented method and a
      validated HPLC-MS/MS method. The Passing-Bablok regression line for MPA and MPAG
      was HPLC-MS/MS=1.14 UPLC-MS/MS-0.14 [ mg L(-1)], r=0.96, and HPLC-MS/MS=0.77 UPLC
      MS/MS+0.50 [ mg L(-1)], r=0.97, respectively. This sample cleanup-free and robust
      LC-MS/MS assay facilitates the rapid, accurate and simultaneous determination of
      MPA and MPAG in human body fluids.

PMID- 20152430
TI  - Threshold detection of aromatic compounds in wine with an electronic nose and a
      human sensory panel.
AB  - An electronic nose (e-nose) based on thin film semiconductor sensors has been
      developed in order to compare the performance in threshold detection and
      concentration quantification with a trained human sensory panel in order to
      demonstrate the use of an e-nose to assess the enologists in an early detection
      of some chemical compounds in order to prevent wine defects. The panel had 25
      members and was trained to detect concentration thresholds of some compounds of
      interest present in wine. Typical red wine compounds such as whiskeylactone and
      white wine compounds such as 3-methyl butanol were measured at different
      concentrations starting from the detection threshold found in literature (in the
      nanograms to milligrams per liter range). Pattern recognition methods (principal
      component analysis (PCA) and neural networks) were used to process the data. The
      results showed that the performance of the e-nose for threshold detection was
      much better than the human panel. The compounds were detected by the e-nose at
      concentrations up to 10 times lower than the panel. Moreover the e-nose was able
      to identify correctly each concentration level therefore quantitative
      applications are devised for this system.

PMID- 20152431
TI  - Eggshell membrane-based solid-phase extraction combined with hydride generation
      atomic fluorescence spectrometry for trace arsenic(V) in environmental water
      samples.
AB  - The eggshell membrane (ESM) contains several surface functional groups such as
      amines, amides and carboxylic groups with potential as SPE adsorbent for the
      retention of target species of interest. In this paper, the potential use of ESM,
      a typical biomaterial, as solid-phase extraction (SPE) adsorbent is evaluated for
      analysis of trace arsenic(V) in environmental water samples in combination with
      hydride generation atomic fluorescence spectrometry (HG-AFS). In order to obtain
      the satisfactory recovery of arsenic(V), various parameters including the
      desorption and enrichment conditions such as pH, the flow rate and the volume of
      sample solution, the amount of ESM and the content of sodium chloride were
      systematically optimized and the effects of co-existed ions were also
      investigated in detail. Under the optimal conditions, arsenic(V) could be easily
      extracted by the ESM packed cartridge and the breakthrough adsorption capacity
      was found to be 3.9 microg g(-1). The favorable limit of detection (LOD) for
      arsenic(V) was found to be 0.001 microg L(-1) with an enrichment factor of 33.3,
      and the relative standard deviations (R.S.Ds) was 2.1% for 0.6 microg L(-1)
      arsenic (n=11). The reproducibility among columns was satisfactory (R.S.D. among
      columns is less than 5%). The proposed method has been successfully applied to
      analysis of arsenic(V) in aqueous environmental samples, which suggests the ESM
      can be an excellent SPE adsorbent for arsenic(V) pretreatment and enrichment from
      real water samples.

PMID- 20152432
TI  - Analysis of ultratrace triorganotin compounds in aquatic organisms by using
      capillary electrophoresis-inductively coupled plasma mass spectrometry.
AB  - A microwave-assisted extraction used to extract trace triorganotin from aquatic
      organisms and a sensitive analytical method for the determination of ultratrace
      triorganotin (namely trimethyltin, triethyltin, tripropyltin and tributyltin)
      with capillary electrophoresis-inductively coupled plasma mass spectrometry were
      firstly described in this study. The extraction method is simple, effective and
      can be used to extract trace triorganotin in aquatic organisms within several
      min. The analytical method has a much lower detection limit of 0.2-0.7 ng Sn/mL
      for triorganotin compounds, and can be used to determine trace triorganotin in
      aquatic organisms directly without any derivatization and preconcentration. Using
      above methods, we have successfully determined trimethyltin, triethyltin,
      tripropyltin and tributyltin in dried Mya arenaria Linnaeus and Corbicula
      fluminea within 17 min with a recovery of 93-104% and a RSD (relative standard
      deviation, n=6) of 2-5%. Our results showed that dried M. arenaria Linnaeus
      contained an extremely high tributyltin of 5.1 microg Sn/g dried weight,
      indicating that it may be a good biomarker for the organotin pollution in ocean.

PMID- 20152433
TI  - Electrochemical oxidation of dopamine and ascorbic acid at a palladium electrode
      modified with in situ fabricated iodine-adlayer in alkaline solution.
AB  - The self-assembled iodine-adlayer was fabricated at the palladium (Pd) electrode
      surface throughout a spontaneous oxidative chemisorption of iodide ions contained
      in an alkaline supporting electrolyte. It enhances the electron transfer kinetics
      for the oxidation of dopamine (DA) and ascorbic acid (AA) and was important to
      separate the peak current of both species with a practical potential difference
      compared with that occurred at the unmodified electrode. The anodic peak currents
      of both species were linearly increased with their respective concentrations
      using linear square stripping voltammetry. The activity of the electrode system
      was further investigated applying chronoamperometry method. The steady-state
      amperometric signal for the oxidation of DA in the presence of iodide ions was
      five times greater than that in its absence. The current-time response was also
      used to evaluate the diffusion coefficient of DA based on Cottrell plot that
      results with a value of 4.19 x 10(-8)m(2)s(-1). The proposed method was
      successfully applied to detect DA and AA in human serum.

PMID- 20152434
TI  - Reversed-phase dispersive liquid-liquid microextraction with central composite
      design optimization for preconcentration and HPLC determination of oleuropein.
AB  - A reversed-phase dispersive liquid-liquid microextraction (RP-DLLME) method was
      developed for the preconcentration and direct HPLC determination of oleuropein in
      olive's processing wastewater (OPW) and olive leaves extracts. In conventional
      DLLME, the sedimented phase is a micro-drop of a chlorinated organic solvent that
      is not compatible with RP-HPLC. Therefore, solvent evaporation and reconstitution
      with an appropriate solvent is often required. In RP-DLLME, this problem was
      overcome by overturning the solvent polarity in the ordinary DLLME and replacing
      the organic solvent with water. A central composite chemometrics design was used
      for multivariate optimization of the effects of five different parameters
      influencing the extraction efficiency of the method. In the optimized conditions,
      a mixture of 1.4 mL of an ethyl acetate extract of sample and 40 microL water (pH
      5.0) was rapidly injected into 5.3 mL of cyclohexane. After centrifugation of the
      formed cloudy mixture, a micro-drop of the aqueous phase was sedimented at the
      conical bottom of the centrifuge tube. This phase, that contained the
      preconcentrated and partially purified analyte, was directly injected into an RP
      HPLC column for analysis. A mean extraction recovery of 102.5 (+/-4.5) % with
      enrichment factors exceeding 38, was obtained for five replicated analysis. The
      detection limit of the method (3 sigma) for OE was 0.02 microg L(-1) for OPW and
      2 x 10(-3) mg kg(-1) for olive leaves samples. The results showed that, RP-DLLME
      is a promising technique which is quick, easily operated and can be directly
      coupled to HPLC.

PMID- 20152435
TI  - Wavelength encoded analytical imaging and fiber optic sensing with pH sensitive
      CdTe quantum dots.
AB  - CdTe quantum dots (QDs), capped with mercaptopropionic acid (MPA), were
      synthesized and the variation of their fluorescence properties (steady state and
      lifetime) with pH was assessed in solution and when immobilized in a sol-gel
      host. Three different sizes of CdTe QDs with excited state lifetimes ranging from
      42 to 48 ns and with emission maximum at 540 nm (QD(540)), 580 nm (QD(580)) and
      625 nm (QD(625)) were selected. The solution pH affects the maximum emission
      wavelength (shifts to higher wavelengths of 23, 24 and 27 nm for QD(540), QD(580)
      and QD(625), respectively), the excited state lifetime and the fluorescence
      intensity in a reversible way. Linearization of the maximum emission wavelength
      variation with the pH allows the estimation of an apparent ionization constant
      (pK(a)) for each QD: 6.5+/-0.1 (QD(540)), 6.1+/-0.5 (QD(580)) and 5.4+/-0.3
      (QD(625)). The variation of the QDs fluorescence properties was further explored
      using confocal laser scanning microscopy allowing the implementation of a new
      calibration method for pH imaging in solution. QDs were successfully immobilized
      on the tip of an optical fiber by dip-coating using sol-gel procedure. The
      immobilized QDs showed a similar pH behaviour to the one observed in solution and
      an apparent lifetime of 80, 68 and 99 ns, respectively. The proposed QDs based
      methodology can be successfully used to monitor pH using wavelength encoded data
      in imaging and fiber optic sensing applications.

PMID- 20152436
TI  - Supramolecular interaction of cucurbit[n]urils and coptisine by
      spectrofluorimetry and its analytical application.
AB  - The supramolecular interaction of a homologous series of cucurbit[n]uril (CB[n],
      n=5, 6, 7, 8) hosts and coptisine (COP) was studied by spectrofluorimetry. All of
      the CB[n]s were found to react with COP to form 1:1 host-guest stable complexes
      and the fluorescence intensity of the complexes was greatly enhanced. The
      apparent association constants of the complexes were 1.44 x 10(4), 1.28 x 10(4),
      1.86 x 10(4) and 1.26 x 10(4)L mol(-1) for CB[5], CB[6], CB[7] and CB[8],
      respectively. In addition, CB[5] and CB[7] exhibited a higher fluorescence signal
      than CB[6] and CB[8]. The fluorescence intensity of the complex with CB[7] was
      enhanced 70-fold compared to that of the studied drug itself. Based on the
      significant enhancement of fluorescence intensity of supramolecular complex, a
      simple, rapid, highly sensitive, and selective spectrofluorimetric method was
      developed for the determination of COP in aqueous solution in the presence of
      CB[7]. At the optimum reaction conditions, a linear relationship was obtained in
      the range from 0.05 to 1700 ng mL(-1) with a detection limit of 0.012 ng mL(-1).
      The proposed method was successfully applied for the determination of the drug in
      urine and serum samples.

PMID- 20152437
TI  - Development of the extraction method for the simultaneous determination of butyl
      , phenyl- and octyltin compounds in sewage sludge.
AB  - The toxicity and bioaccumulation of organotin compounds (OTCs) led to the
      development of sensitive and selective analytical methods for their
      determination. In the past much attention was assigned to the study of OTCs in
      biological samples, water and sediments, coming mostly from marine environment.
      Little information about OTCs pollution of terrestrial ecosystems is available.
      In order to optimise the extraction method for simultaneous determination of
      butyl-, phenyl- and octyltin compounds in sewage sludge five different
      extractants (tetramethylammonium hydroxide, HCl in methanol, glacial acetic acid,
      mixture of acetic acid and methanol (3:1), and mixture of acetic acid, methanol
      and water (1:1:1)), the presence or not of a complexing agent (tropolone), and
      the use of different modes of extraction (mechanical stirring, microwave and
      ultrasonic assisted extraction) were tested. Extracted OTCs were derivatised with
      sodium tetraethylborate and determined by gas chromatography coupled with mass
      spectrometer. Quantitative extraction of butyl-, phenyl- and octyltin compounds
      was obtained by the use of glacial acetic acid as extractant and mechanical
      stirring for 16h or sonication for 30 min. The limits of detection and
      quantification for OTCs investigated in sewage sludge were in the ng S ng(-1)
      range.

PMID- 20152438
TI  - Facile, sensitive and selective fluorescence turn-on detection of HSA/BSA in
      aqueous solution utilizing 2,4-dihydroxyl-3-iodo salicylaldehyde azine.
AB  - A novel fluorescence turn-on detection method of human serum albumin (HSA) and
      bovine serum albumin (BSA) in aqueous solution is investigated using 2,4
      dihydroxyl-3-iodo salicylaldehyde azine (DISA). Upon the addition of DISA to
      HSA/BSA solution, a fluorescence turn-on effect at 529 nm can be observed with a
      large stokes shift of approximately 129 nm based on hydrophobic binding-mode
      between protein and dye. Under the optimal condition, the linear ranges of
      fluorescence intensity for HSA and BSA are 0.1-30 microg mL(-1) with the relative
      correlation coefficient of R(2)=0.991 (n=10) and 0.3-50 microg mL(-1) with
      R(2)=0.997 (n=10); and the detection limits for HSA and BSA based on IUPAC
      (C(DL)=3S(b)/m) are 20 ng mL(-1) and 50 ng mL(-1), respectively.

PMID- 20152439
TI  - Determination of cadmium with a sequential injection lab-on-valve by anodic
      stripping voltammetry using a nafion coated bismuth film electrode.
AB  - This work exploited a sequential injection lab-on-valve (LOV) system for the
      determination of cadmium by anodic stripping voltammetry (ASV). A miniaturized
      electrochemical flow cell (EFC) was fabricated in LOV, in which a nafion coated
      bismuth film electrode was used as working electrode. The cadmium was
      electrodeposited on the electrode surface in bismuth solution, and measured with
      the subsequential stripping scan. Under optimal conditions, the proposed system
      responded linearly to cadmium concentrations in a range 2.0-100.0 microg L(-1).
      The detection limit of this method was found to be 0.88 microg L(-1). By loading
      a sample volume of 800 microL, a sampling frequency of 22 determinations h(-1)
      was achieved. The repeatability expressed as relative standard derivation
      (R.S.D.) was 3.65% for 20 microg L(-1) cadmium (n=11). The established method was
      applied to analysis of trace cadmium in environmental water samples and the
      spiked recoveries were satisfactory.

PMID- 20152440
TI  - A high-performance fluorosensor for pH measurements between 6 and 9.
AB  - This study presents a high-performance ratiometric pH optode based on the
      fluorophore 6,8-dihydroxypyrene-1,3-disulfonic acid (DHPDS). The two pH-sensitive
      terminal hydroxy groups of DHPDS facilitated dual excitation/dual emission (F(1):
      lambda(1,ex)=420 nm, lambda(1,em)=462 nm; F(2): lambda(2,ex)=470 nm,
      lambda(2,em)=498 nm) properties for ratiometric (R(F1,F2)=F(1)/F(2))
      normalization of sensor signal. The sensor demonstrated an exponentially
      decreasing ratiometric response with increasing pH, with a linear correlation
      (R(2)=0.9936) between (10)log(R(F1,F2)) and pH within the pH interval 6-9.
      Precision determined as the IUPAC pooled standard deviation for the pH values
      6.00, 7.01 and 9.01, was 0.0057 pH units for the fluorosensor and 0.0054 for a
      commercially available pH electrode used for comparison. Between the end-points
      of calibration at pH 7.01, the precision of the sensor was 0.0037 pH units.
      Effects from changes in ionic strength (I(tot), 10-700 mM) were more pronounced
      for the electrode, with a linear (R(2)=0.9976) increase in response
      (deltaE/deltapH) with increasing I(tot). The DHPDS-based fluorosensor, however,
      retained sensitivity (delta(10)log(R(F1,F2))/deltapH=0.8024+/-0.0145), though
      with an overall increase in ratiometric signal with increasing I(tot). The
      preserved sensitivity despite changes in ionic strength was possibly a
      consequence from the dual photo-acidic properties of DHPDS. Analytical
      characteristics of immobilized DHPDS therefore not only facilitated high
      performance measurements over a wide pH range, but also opened for
      straightforward simultaneous measurements of pH and ionic strength.

PMID- 20152441
TI  - Rapid qualitative and quantitative ultra high performance liquid chromatography
      method for simultaneous analysis of twenty nine common phenolic compounds of
      various structures.
AB  - Twenty nine phenolic compounds comprising nine phenolic acids, sixteen flavonoids
      (including eight tea catechins, glycosides and aglycones), four coumarins plus
      caffeine were analysed within 20 min using ultra high performance liquid
      chromatography (UHPLC) with PDA detection. UHPLC system was equipped with C18
      analytical column (100 mm x 2.1mm, 1.7 microm), utilising 0.1% formic acid and
      methanol mobile phase in the gradient elution mode. The developed method was
      tested for the system suitability: resolution, asymmetry factor, peak capacity,
      retention time repeatability and peak area repeatability. The method was fully
      validated in the terms of linearity (r(2)>0.9990 for all 30 compounds), range
      (typically 1-100 mg L(-1)), LOD, LOQ, inter/intra-day precision (<3% and <9%
      respectively) and inter/intra-day accuracy (typically 100+/-10%). Subsequently
      the method was applied to the identification (spectral information and peak
      purity calculations were profited) and quantification of phenolic compounds and
      caffeine present in tea infusions and extracts.

PMID- 20152442
TI  - Evaluating use of ferricyanide-mediated respiration bioassays to quantify
      stimulatory and inhibitory effects on Escherichia coli populations.
AB  - A number of recent studies have utilised ferricyanide as a respiratory mediator
      for microbial-based assays for determining water quality parameters such as
      biochemical oxygen demand (BOD) and toxicity. The majority of assays published to
      date obtain a result by determining the difference in ferrocyanide accumulation
      between a test sample and one or more control samples. However, a validation of
      the relationship between ferrocyanide accumulation and standard measures of cell
      density or viability has not yet been performed. To this end, a rapid microbially
      catalysed ferricyanide-mediated respiration (FM-RES) assay was compared with
      standard plate count (SPC) and spectrophotometer (OD(600)) measurements on a
      growing batch culture of Escherichia coli. Good agreement was observed between
      all techniques, with predictable deviations noted in different phases of the
      growth curves. Standardised FM-RES assays showed excellent correlations with the
      SPC method under controlled conditions, indicating that short-term changes in
      microbial activity are due to a change in per-cell respiration, rather than
      changes in cell numbers. The FM-RES assay was then used to observe the changes in
      the respiration of E. coli induced by the addition of a glucose-glutamic acid
      (GGA) mixture, 3,5-dichlorophenol (3,5-DCP) and Ag(+) in various combinations and
      concentrations. Stimulation of respiration was pronounced in the presence of GGA
      while both 3,5-DCP and, in particular, Ag(+) demonstrated inhibitory respiratory
      effects. The results highlight the validity and suitability of ferricyanide
      mediated respiration bioassays, with appropriate modification, to monitor either
      stimulatory effects on microbial populations, such as occurs with BOD, or
      inhibitory effects, such as occurs with toxicity assays.

PMID- 20152443
TI  - Determination of progesterone (P4) from bovine serum samples using a microfluidic
      immunosensor system.
AB  - Progesterone (P4) is a steroidal hormone with a vital role in the maintenance of
      human and animal health. This paper describes the development of an immunosensor
      coupled to glassy carbon (GC) electrode and integrated to a microfluidic system
      to quantify P4 from bovine serum samples in a fast and sensitive way. The serum
      samples spiked with a given P4 concentration and a given P4 concentration bound
      to horseradish peroxide (HPR) were simultaneously added and, therefore, they
      competed immunologically with sheep monoclonal anti-P4 antibodies that were
      immobilized at a rotating disk. HRP in the presence of hydrogen peroxide
      (H(2)O(2)) catalyzes the chatecol (H(2)Q) oxidation to benzoquinone (Q). Its
      reverse electrochemical reduction to H(2)Q can be detected at a GC electrode
      surface at -0.15 V by chronoamperometric measurements. These current responses
      are proportional to the enzyme activity and inversely proportional to the P4
      amount present in bovine serum samples. This P4 immunosensor showed a linear
      working range from 0.5 to 12.5 ng mL(-1). The detection (DL) and quantification
      (QL) limits were 0.2 and 0.5 ng mL(-1), respectively. The electrochemical
      immunosensor had a higher sensitivity than the ELISA method using conventional
      spectrophotometric detections. However, both methods allowed us to obtain similar
      detection limits. The immunosensor allowed us to make up to 100 determinations on
      different samples without any previous pre-treatment. This behavior proved to be
      suitable to detect P4 in routine veterinary, clinical, biological, physiological,
      and analytical assays.

PMID- 20152444
TI  - Serum-protein effects on the detection of the beta-blocker propranolol by ion
      transfer voltammetry at a micro-ITIES array.
AB  - In this work, the effect of the serum protein, bovine serum albumin (BSA), on the
      detection of propranolol in artificial serum by ion-transfer voltammetry at an
      array of micro-interfaces between two immiscible electrolyte solutions
      (microITIES) is presented. Cyclic voltammetry (CV), differential pulse
      voltammetry (DPV), and differential pulse stripping voltammetry (DPSV) were
      examined for the detection of low concentrations of propranolol. Both CV and DPV
      had an interference effect from BSA, manifested as lower currents in the presence
      of the protein. DPSV proved to be the most effective technique, enabling the
      detection of 0.05 microM propranolol in the presence of BSA. The DPSV method
      employed a preconditioning step as well as a preconcentration step followed by
      the analytical signal generation step. The latter was based on the back-transfer
      of the drug across the microITIES. The preconcentration step was crucial to
      prevention of the adverse effects of BSA on the voltammetric detection. These
      results demonstrate that serum-protein effects on drug detection at low
      concentrations can be eliminated by use of DPSV at arrays of microITIES. CVs of
      propranolol with increasing concentrations of BSA revealed the influence of the
      drug-protein binding interaction, with decreases in current but no change in
      transfer potential. Therapeutic concentrations of propranolol were detected,
      demonstrating the viability of this approach for bioanalytical investigations.

PMID- 20152445
TI  - Electroanalytical determination of estriol hormone using a boron-doped diamond
      electrode.
AB  - A boron-doped diamond (BDD) electrode was used for the electroanalytical
      determination of estriol hormone in a pharmaceutical product and a urine sample
      taken during pregnancy by square-wave voltammetry. The optimized experimental
      conditions were: (1) a supporting electrolyte solution of NaOH at a pH of 12.0,
      and (2) a frequency of 20 Hz, a pulse height of 30 mV and a scan increment of 2
      mV (for the square-wave parameters). The analytical curve was linear in the
      concentration range of 2.0 x 10(-7) to 2.0 x 10(-5) mol L(-1) (r=0.9994), with a
      detection limit of 1.7 x 10(-7) mol L(-1) and quantification limit of 8.5 x 10(
      7) mol L(-1). Recoveries of estriol were in the range of 98.6-101.0%, for the
      pharmaceutical sample, and 100.2-103.4% for the urine sample, indicating no
      significant matrix interference effects on the analytical results. The accuracy
      of the electroanalytical methodology proposed was compared to that of the
      radioimmunoassay method. The values for the relative error between the proposed
      and standard methods were -7.29% for the determination of estriol in the
      commercial product and -4.98% in a urine sample taken during pregnancy. The
      results obtained suggest a reliable and interesting alternative method for
      electroanalytical determination of estriol in pharmaceutical products and urine
      samples taken during pregnancy using a boron-doped diamond electrode.

PMID- 20152446
TI  - Quantitative determination of oxybutynin hydrochloride by spectrophotometry,
      chemometry and HPTLC in presence of its degradation product and additives in
      different pharmaceutical dosage forms.
AB  - Simple, accurate, sensitive and validated UV spectrophotometric, chemometric and
      HPTLC-densitometric methods were developed for determination of oxybutynin
      hydrochloride (OX) in presence of its degradation product and additives in its
      pharmaceutical formulations. Method A is the first derivative of ratio spectra
      (DD(1)) which allows the determination of OX in presence of its degradate in pure
      form and tablets by measuring the peaks amplitude at 216 nm. Method B and C are
      principal component regression (PCR) and partial least-squares (PLS) for
      determination of OX in presence of its degradate in pure form, tablets and syrup.
      While, the developed high performance thin layer chromatography HPTLC
      densitometric method was based on the separation of OX from its degradation
      product, methylparaben and propylparaben followed by densitometric measurement at
      220 nm which allows the determination of OX in pure form, tablets and syrup. The
      separation was achieved using HPTLC silica gel F(254) plates and
      chloroform:methanol:ammonia solution:triethylamine (100:3:0.5:0.2, v/v/v/v) as
      the developing system. The accuracy, precision and linearity ranges of the
      developed methods were determined. The results obtained were statistically
      compared with each other and to that of a reported HPLC method, and there was no
      significant difference between the proposed methods and the reported method
      regarding both accuracy and precision.

PMID- 20152447
TI  - SiO2 coated Fe3O4 magnetic nanoparticle dispersed multiwalled carbon nanotubes
      based amperometric glucose biosensor.
AB  - A new type of amperometric glucose biosensor based on silicon dioxide coated
      magnetic nanoparticle decorated multiwalled carbon nanotubes
      (Fe(3)O(4)@SiO(2)/MWNTs) on a glassy carbon electrode (GCE) has been developed.
      MWNTs have been synthesized by catalytic chemical vapour decomposition (CCVD) of
      acetylene over rare earth (RE) based AB(3) alloy hydride catalyst. The as-grown
      MWNTs have been purified and further functionlized. Functionalized MWNTs have
      been decorated with magnetic Fe(3)O(4) nanoparticles which have been uniformly
      coated with biocompatible SiO(2) using a simple chemical reduction method. The
      characterization of magnetic nanoparticle modified MWNTs have been done by X-ray
      diffraction (XRD), Fourier transform infra red spectroscopy (FT-IR), scanning
      electron microscope (SEM), transmission electron microscope (TEM), vibrating
      sample magnetometer (VSM), energy dispersive X-ray analysis (EDX) and UV-vis
      spectroscopy. Amperometric biosensor has been fabricated by the deposition of
      glucose oxidase (GOD) over Nafion-solubilized Fe(3)O(4)@SiO(2)/MWNTs electrode.
      The resultant bioelectrode retains its biocatalytic activity and offers fast and
      sensitive glucose quantification. The performance of the biosensor has been
      studied using cyclic voltammetry and amperometry and the results have been
      discussed. The fabricated glucose biosensor exhibits a linear response from 1
      microM to 30 mM with an excellent detection limit of 800 nM indicating the
      potential applications in food industries.

PMID- 20152448
TI  - Novel fluorimetric bulk optode membrane based on 5,8-bis((5'-chloro-8'-hydroxy-7'
      quinolinyl)methyl)-2,11-dithia-5,8-diaza-2,6-pyridinophane for selective
      detection of lead(II) ions.
AB  - A novel fluorescence chemical sensor for the highly sensitive and selective
      determination of Pb(2+) ions in aqueous solutions is described. The preliminary
      potentiometric and spectrofluorimetric complexation studies in solution revealed
      that the lipophilic ligand 5,8-bis((5'-chloro-8'-hydroxy-7'-quinolinyl)methyl)
      2,11-dithia-5,8-diaza-2,6-pyridinophane (L2) forms a highly stable and selective
      [PbL2](2+) and [Pb(L2)(2)](2+) complexes which results in a strong fluorescence
      quenching of the ligand. Thus, a novel fluorescence Pb(2+) sensing system was
      prepared by incorporating L2 as a neutral lead-selective fluoroionophore in the
      plasticized PVC membrane containing tetrakis(p-chlorophenyl) borate as a
      liphophilic anionic additive. The response of the sensor is based on the strong
      selective fluorescence quenching of L2 by Pb(2+) ions. At pH 5.5, the proposed
      sensor displays a calibration curve over a wide concentration range of 3.0 x 10(
      7) to 2.5x 10(-2)M with a relatively fast response time of less than 5 min. In
      addition to high stability, reversibility and reproducibility, the sensor shows a
      unique selectivity towards Pb(2+) ion with respect to common coexisting cations.
      The proposed fluorescence optode was successfully applied to the determination of
      lead in plastic toys and tap water samples.

PMID- 20152449
TI  - Tetradecyl(trihexyl)phosphonium chloride ionic liquid single-drop microextraction
      for electrothermal atomic absorption spectrometric determination of lead in water
      samples.
AB  - A highly efficient single-drop microextraction (SDME) procedure using a low-cost
      room temperature ionic liquid (RTIL), i.e., tetradecyl(trihexyl)phosphonium
      chloride (CYPHOS IL 101), for Pb determination at trace levels in real water
      samples was developed. Lead was chelated with 2-(5-bromo-2-pyridylazo)-5
      diethylaminophenol (5-Br-PADAP) reagent and extracted into a 4 microL microdrop
      of CYPHOS IL 101. The RTIL drop was directly injected into the graphite furnace
      of the electrothermal atomic absorption spectrometer (ETAAS). Under optimal
      microextraction conditions, a preconcentration factor of 32 was achieved with
      only 1.5 mL of sample resulting in a phase-volume ratio of 375. The limit of
      detection (LOD) obtained was 3.2 ng L(-1) and the relative standard deviation
      (RSD) for 10 replicates at 0.5 microg L(-1) Pb(2+) concentration level was 4.9%,
      calculated at peak heights. The calibration graph was linear from concentration
      levels near the detection limits up to at least 4.5 microg L(-1) with a
      correlation coefficient of 0.9996. The accuracy of the methodology was evaluated
      by analysis of a certified reference material (CRM). The method was successfully
      applied to the determination of Pb in tap, mineral, well and river water samples.

PMID- 20152450
TI  - Determination of volatile organic compounds in contaminated air using
      semipermeable membrane devices.
AB  - Semipermeable membrane devices (SPMDs) were evaluated as passive samplers for the
      determination of 26 volatile organic compounds (VOCs) in contaminated air of
      occupational environments. A direct methodology based on the use of head-space
      gas chromatography-mass spectrometry (HS-GC-MS) was developed for VOCs
      determinations in SPMDs, without any sample pre-treatment and avoiding the use of
      solvents. A desorption temperature of 150 degrees C for 10 min was sufficient for
      a sensitive VOCs determination providing limits of detection in the range of 15
      ng SPMD(-1) for 21 of 26 studied compounds. Linear and equilibrium uptake models
      were established for each VOC from compound isotherms. Highly volatile compounds
      were slightly absorbed and moderately volatile compounds were strongly absorbed
      by SPMDs. This study is the first precedent of the use of SPMDs for the
      simultaneous sampling of a wide number of VOCs. The use of SPMDs is a simple and
      low cost alternative to ordinary sampling devices such as Radiello diffusive
      samplers or badge-type solid-phase supports.

PMID- 20152451
TI  - A fast assay of water hardness ions based on alkaline earth metal induced
      coacervation (HALC).
AB  - In this work, a rapid assay of water hardness is presented based on the formation
      of a coacervate phase made up of multilamellar vesicles and close bilayers
      produced upon the reaction of alkaline earth metals with a carboxylate anionic
      surfactant in the presence of a co-surfactant (methanol). The procedure exploits
      the light scattering abilities of the coacervate phase which can be
      logarithmically linked to total hardness as CaCO(3) equivalents via
      spectrophotometric detection at 350 nm. The method, abbreviated as HALC, stemming
      from hardness by alkaline earth metal coacervation, is straightforwardly
      applicable overcoming the requirement for regulation of the experimental
      parameters involved in the determination procedure. In total, 28 water samples
      with various matrix compositions and hardness contents were analyzed with
      satisfactory accuracy as evidenced by comparison of the results with EDTA
      complexometric titration. The method is free from interferences from
      environmentally significant metal cations and inorganic anions affording
      detection limits as low as 13.5 mg L(-1) CaCO(3) with the aid of a correction
      factor, which is determined by the non-linear absorbance properties of the
      solution mixture, and satisfactory reproducibility (RSD=4.21-8.08%).

PMID- 20152452
TI  - Vortex-assisted liquid-liquid microextraction of octylphenol, nonylphenol and
      bisphenol-A.
AB  - A new and fast equilibrium-based solvent microextraction technique termed vortex
      assisted liquid-liquid microextraction (VALLME) has been developed and used for
      the trace analysis of octylphenol, nonylphenol and bisphenol-A in water and
      wastewater samples. According to VALLME, dispersion of microvolumes of a low
      density extractant organic solvent into the aqueous sample is achieved by using
      for the first time vortex mixing, a mild emulsification procedure. The fine
      droplets formed could extract target analytes towards equilibrium faster because
      of the shorter diffusion distance and larger specific surface area. Upon
      centrifugation the floating extractant acceptor phase restored its initial single
      microdrop shape and was used for high-performance liquid chromatographic
      analysis. Different experimental parameters were controlled and the optimum
      conditions found were: 50 microl of octanol as the extractant phase; 20 ml
      aqueous donor samples; a 2 min vortex extraction time with the vortex agitator
      set at a 2500 rpm rotational speed; centrifugation for 2 min at 3500 rpm; no
      ionic strength or pH adjustment. The calculated calibration curves gave high
      levels of linearity yielding correlation coefficients (r(2)) greater than 0.9935.
      The repeatability and reproducibility of the proposed method were found to be
      good and the limits of the detection were calculated in the low microg l(-1)
      level ranging between 0.01 and 0.07 microg l(-1). Matrix effects were determined
      by applying the proposed method to spiked tap, river water and treated municipal
      wastewater samples. The proposed method was finally applied to the determination
      of target pollutants in real wastewater effluent samples using the standard
      addition method.

PMID- 20152453
TI  - Influence of the solvent quality on the AhR mediated Procept assay measurement of
      dioxin and dioxin-like compounds.
AB  - Polychlorodibenzo-p-dioxins, polychorodibenzofurans and "dioxin-like"
      polychlorinated biphenyls are widespread persistent organic pollutants sharing a
      similar toxicological pathway mediated by the aryl-hydrocarbon receptor (AhR).
      Since the confirmatory method for their measurement at trace levels in complex
      matrices (using isotopic dilution and gas chromatography-high resolution mass
      spectrometry) remains time and cost-consuming, growing efforts of the scientific
      community have been focused on the development of screening approaches, including
      AhR mediated assays. Unfortunately, AhR ligands are highly diverse and
      agonistic/antagonistic effects can be observed on procedural blanks and/or sample
      extracts. In this study, the influence of solvent grade quality on the response
      of a DNA-binding AhR mediated assay used for screening dioxins has been
      investigated. Our results demonstrated a very critical impact of this parameter
      with both strong agonistic and antagonistic effects observed for any tested
      solvent lot. A small silver nitrate silica column removed partly these
      interfering compounds and then can be recommended as final purification step.
      Some preferable grades can be identified and selected in order to guarantee the
      best possible performances. However, it appears necessary to test every new lot,
      even if a grade appeared previously compliant.

PMID- 20152454
TI  - Fast multi-element screening of non-digested biological materials by slurry
      introduction to ICP-AES.
AB  - A fast method for direct multi-element analysis of non-digested biological
      samples is presented. The only sample preparation needed is 1 min homogenization
      with a Polytron mixer in a small volume of neutral phosphate buffer saline
      solution (PBS). The total time for analysis (sample preparation and measurement)
      is 4 min only. This "mix and measure" method can handle large sample loads of
      biological samples and thus minimize dilution of trace elements. For example 100%
      whole blood was introduced without any clogging of the introduction system or
      extinguishing of the plasma. In 70% (v/v) whole blood reference material 14 of 16
      analytes were quantified within +/-10% (Al, B, Ba, Ca, Cu, Fe, Mg, Mn, P, Pb, S,
      Sr, Ti and Zn) and two semi-quantified within +/-20% (Cd and K). Fresh bovine
      liver was also analyzed with the same method and 7 of 9 analytes were quantified
      in 5% (w/v) liver slurry. Three different nebulizers were tested, Glass Expansion
      Concentric (GEC) of Meinhard type, Cross Flow and Burgener T2100 and they
      performed roughly equally well in giving quantitative results for the slurries
      but the sensitivity was better with the GEC. The stability of the plasma was
      studied by evaluating the ratio of Mg 280.270 nm and Mg 285.213 nm lines. When
      increasing the sample load from 20 to 100% (v/v) of whole blood and from 0.5 to
      10% (w/v) of bovine liver the Mg ratio was constant within a few percent for all
      of the nebulizer tested. The ratio of the sensitivity between GEC and Burgener
      T2100 was studied and the ratio increased with the energy sum for atomic and
      ionic lines separately.

PMID- 20152455
TI  - Headspace solid-phase microextraction of oil matrices heated at high temperature
      and phthalate esters determination by gas chromatography multistage mass
      spectrometry.
AB  - A solvent-free analytical approach based on headspace solid-phase microextraction
      (SPME) of oil matrices heated at high temperatures coupled to gas chromatography
      with mass spectrometry detector (GC-ion trap) has been developed for the
      determination of phthalic acid esters (PAEs) in oil matrices without sample
      manipulation. For this study, three fibers, i.e., 85 microm-polyacrylate (PA),
      50/30 microm-divinylbenzene-carboxen-polydimethylsiloxane (DVB/CAR/PDMS) and 100
      microm-polydimethylsiloxane (PDMS) were tested. Variables affecting the SPME
      headspace composition such as incubation sample temperature, sample incubation
      time and fiber exposition time were optimized. The optimal values found were 250
      degrees C for sample incubation temperature and 30 min for incubation and
      extraction time. PA fiber was not suitable for the lightest polar phthalates
      which showed poor extraction and repeatability values. PDMS fiber had very poor
      response for some of the heavier and non-polar phthalates, whereas DVB/CAR/PDMS
      fiber showed the best response and repeatability values for the majority of the
      phthalates studied. The main benefit of the analytical method proposed is the
      absence of sample manipulation and hence avoidance of possible contamination
      coming from glassware, environment, solvents and samples.

PMID- 20152456
TI  - Simultaneous determination of carbonyl compounds and polycyclic aromatic
      hydrocarbons in atmospheric particulate matter by liquid chromatography-diode
      array detection-fluorescence detection.
AB  - Simultaneous analysis of 24 carbonyl compounds (alkanals, unsaturated,
      dicarbonylic and aromatic aldehydes and ketones) derivatized with 2,4
      dinitrophenylhydrazine and 16 polycyclic aromatic hydrocarbons (PAHs) using a
      photodiode-array (PDA) and a fluorescence (FL) detector in series is proposed.
      The separation is carried out with a reversed-phase column and gradient elution
      using four solvents (acetonitrile, water, tetrahydrofuran and methanol) in less
      than 35 min. Several critical pairs of carbonyl compounds with 3 and 4 carbon
      atoms and different functional groups, isomers of tolualdehyde, aromatic and
      aliphatic aldehydes were conditional on the gradient elution. Common pre
      treatment for two groups of compounds consists in a step of extraction and
      derivatization in aqueous medium and a further clean-up using a polymeric phase
      SPE and concentration in a mixture of dichloromethane:methanol. A pre
      concentration factor of 50 was achieved by this procedure. Acetone and
      formaldehyde blanks were minimized and remain controlled with a specific cleaning
      of glass material and washing the SPE cartridge. The limits of detection (LOD)
      ranged from 0.006 to 0.18 ng mL(-1) for PAHs and from 2.4 to 10.1 ng mL(-1) for
      carbonyl compounds and method precision was <or=15% for all analysed compounds.
      Recoveries were within the range of 95-104% for PAHs except for more volatile
      compounds (acenaphthene and fluorene) and within the range of 72-113% for
      carbonyl compounds. The method was applied in water-soluble fraction of PM(10)
      (atmospheric particulate matter with an aerodynamic diameter less than 10 microm)
      and the spectral contrast technique was used in the identification of carbonyl
      compounds.

PMID- 20152457
TI  - An rhodamine-based fluorescence probe for iron(III) ion determination in aqueous
      solution.
AB  - An "off-on" rhodamine-based fluorescence probe for the selective signaling of
      Fe(III) has been designed exploiting the guest-induced structure transform
      mechanism. This system shows a sharp Fe(III)-selective fluorescence enhancement
      response in 100% aqueous system under physiological pH value and possesses high
      selectivity against the background of environmentally and biologically relevant
      metal ions including Al(III), Cd(II), Fe(II), Co(II), Cu(II), Ni(II), Zn(II),
      Mg(II), Ba(II), Pb(II), Na(I), and K(I). Under optimum conditions, the
      fluorescence intensity enhancement of this system is linearly proportional to
      Fe(III) concentration from 6.0 x 10(-8) to 7.2 x 10(-6) mol L(-1) with a
      detection limit of 1.4 x 10(-8) mol L(-1).

PMID- 20152458
TI  - A novel molecularly imprinted solid-phase microextraction fiber coupled with high
      performance liquid chromatography for analysis of trace estrogens in fishery
      samples.
AB  - The combination of molecular imprinting and solid-phase microextraction (SPME)
      technique provides a powerful sample preparation tool in terms of selectivity,
      simplicity, and flexibility. This paper reports a novel molecularly imprinted
      polymer (MIP) coated SPME fiber with 17beta-estradiol as template by improved
      multiple co-polymerization method. The obtained fiber exhibits excellent
      characteristics such as high porosity, good thermal and chemical stability.
      Extraction performance shows that the MIP-coated fiber has stronger affinity to
      the template molecule as compared with the commercial SPME fibers and the control
      polymer-coated fiber without addition of template. Owing to the shape and
      structural compatibility, the obtained fiber also demonstrated specific
      selectivity to the structural related compounds of 17beta-estradiol, such as
      estriol, estrone and 17 alpha-ethynylestradiol, and thus can be applied to
      simultaneous determination of these estrogens from complex samples coupled with
      high performance liquid chromatography. The variables that influence extraction
      were investigated. The MIP-coated fiber demonstrated its efficiency for
      extraction of estrogens in fishery samples. The detection limits were in the
      range of 0.98-2.39 microg L(-1), and the recoveries were 80.0-83.6% and 85.0
      94.1% for fish and shrimp tissue samples, respectively.

PMID- 20152459
TI  - Evaluation of a new electrolytic cold vapor generation system for mercury
      determination by AFS.
AB  - In this study we firstly report a new electrolytic cold vapor generation system
      for mercury determination on Pt/Ti cathode in the presence of organic acid
      catholyte. Comparing with the traditional inorganic acid, formic acid increased
      the signal intensity of Hg vapor from electrolytic generation on Pt cathode and
      reduced the impact of cathode erosion on the stability of signal intensity.
      Moreover, formic acid has better interference tolerance. The introduction
      location for carrier gas is probably the most important factor that influences
      the signal intensity of Hg from electrolytic vapor generation. The effects of the
      electrolytic conditions and interference ions on the ECVG have been studied.
      Under the optimized conditions, the detection limit (3 sigma) of Hg (II) in
      aqueous solutions is 1.4 ng L(-1); a relative standard deviation of 2.3% for 1
      microg L(-1) Hg was obtained. The accuracy of this method was verified by the
      determination of mercury in the certified reference materials. This system has
      been applied satisfactorily to the determination of Hg in Traditional Chinese
      Medicines samples.

PMID- 20152460
TI  - Electrochemical biosensor based on nanogold-modified poly-eriochrome black T film
      for BCR/ABL fusion gene assay by using hairpin LNA probe.
AB  - A novel electrochemical biosensor is described for detection of breakpoint
      cluster region gene and a cellular abl (BCR/ABL) fusion gene in chronic
      myelogenous leukemia (CML) by using thiolated-hairpin locked nucleic acids (LNA)
      as the capture probe. The hairpin LNA probe was immobilized on the nanogold
      (NG)/poly-eriochrome black T (EBT) film-modified glassy carbon electrode (GCE).
      The immobilized LNA probe could selectively hybridize with its target DNA on
      LNA/NG/EBT/GCE surface. The immobilization and hybridization of the LNA probe
      were characterized with cyclic voltammetry and electrochemical impedance
      spectroscopy. The hybridization of the immobilized LNA probe with the target DNA
      was detected by differential pulse voltammetry with the electroactive methylene
      blue as an indicator. The results indicated this new method has excellent
      specificity for single-base mismatch and complementary after hybridization, and a
      high sensitivity. This novel electrochemical biosensor has been used for assay of
      PCR real sample with satisfactory result.

PMID- 20152461
TI  - New method for speciation analysis of aluminium fluoride complexes by HPLC-FAAS
      hyphenated technique.
AB  - Speciation analysis of aluminium in the presented system of HPLC-FAAS hyphenated
      technique lasts 4min. Using the bifunctional column in model analysis and using
      the calculation methods for modelling using the Mineql program enabled the
      authors to presume that particular forms will be subjected to elution in the
      following order: (1) AlF(2)(+) and AlF(4)(-), (2) AlF(2+) and AlF(3)(0) and (3)
      Al(3+). Based on the obtained results for model solutions, the presented method
      enables the determination of aluminium fluoride complexes and Al(3+) speciation
      form. The study compares the tendency of occurrence variability of aluminium
      fluoride complexes and Al(3+) form, determined based on the results obtained
      using the HPLC-FAAS hyphenated technique with the trend defined based on the
      Mineql program calculation method. The method was successfully applied to soil
      samples.

PMID- 20152462
TI  - An on-line preconcentration/separation system for the determination of bismuth in
      environmental samples by FAAS.
AB  - An on-line preconcentration procedure for the determination of bismuth by flame
      atomic absorption spectrometry (FAAS) has been described. Lewatit TP-207
      chelating resin, including iminodiacetate group, packed in a minicolumn was used
      as adsorbent material. Bi(III) was sorbed on the chelating resin, from which it
      could be eluted with 3 mol L(-1) HNO(3) and then introduced directly to the
      nebulizer-burner system of FAAS. Best preconcentration conditions were
      established by testing different resin quantities, acidity of sample, types of
      eluent, sample and eluent solution volumes, adsorption and elution flow rates,
      and effect of interfering ions. The detection limit of the method was 2.75 microg
      L(-1) while the relative standard deviation was 3.0% for 0.4 microg mL(-1)
      Bi(III) concentration. The developed method has been applied successfully to the
      determination of bismuth in pharmaceutical cream, standard reference materials
      and various natural water samples with satisfactory results.

PMID- 20152463
TI  - Nitrite sensor based on multilayer film of Dawson-type tungstophosphate alpha
      K7)[H4PW18O62]x18H2O immobilized on glassy carbon.
AB  - A nitrite sensor based on immobilized Dawson-type tungstophosphate alpha
      K(7)[H(4)PW(18)O(62)].18H(2)O (PW(18)) in multilayers of charged polyelectrolyte
      poly(allylamine hydrochloride) (PAH) on a glassy carbon electrode is described. A
      nitrite sensor manufactured with 10 layers has a sensitivity of approximately 4
      nA/microM nitrite, fast response time (<6s), low detection limit ( approximately
      0.1 microM), high selectivity towards endogenous interferences such as nitrate
      and molecular oxygen, a linear range from 0.1 microM to at least 20mM nitrite and
      was stable for at least 2 months. In addition, such nitrite sensors can operate
      in a pH range from 1 to 9, and the sensitivity can be increased by increasing the
      number of layers at the expense of increasing the response time.

PMID- 20152464
TI  - NMR and chemometrics in tracing European olive oils: the case study of Ligurian
      samples.
AB  - An NMR and chemometric analytical approach to classify extra virgin olive oils
      according to their geographical origin was developed within the European TRACE
      project (FP6-2003-FOOD-2-A, contract number: 0060942). Olive oils (896 samples)
      of three consecutive harvesting years (2005, 2006, and 2007) coming from
      Mediterranean areas were analyzed by (1)H NMR spectroscopy. Olive oil samples
      from Liguria, an Italian region, were chosen as a case study and PLS-DA and SIMCA
      modeling analyses were used to build up statistical models both to discriminate
      between Ligurian and non-Ligurian olive oils and to define the Ligurian olive oil
      class to confirm the declared provenience.

PMID- 20152465
TI  - Selective detection of dopamine in the presence of ascorbic acid using carbon
      nanotube modified screen-printed electrodes.
AB  - This work reports on the performance of carbon nanotube modified screen-printed
      electrodes (SPE-MWCNT) for the selective determination of dopamine (DA) in the
      presence of ascorbic acid (AA) by adsorptive stripping voltammetry (AdSV).
      Several operating conditions and parameters were examined including the
      electrochemical pre-treatment and the previous AA interaction and DA accumulation
      in the presence AA at physiological conditions. Under the chosen conditions, DA
      peak current of differential pulse voltammograms increases linearly with DA
      concentration in the range of 5.0 x 10(-8) to 1.0 x 10(-6) mol L(-1) with a limit
      of detection of 1.5 x 10(-8) mol L(-1) in connection with 600s accumulation time.
      The sensitivity obtained for DA was independent from the presence or absence of
      AA; therefore, the proposed method can be readily applied to detect DA in real
      samples. The proposed methodology was successfully used for the quantification of
      DA in urine samples.

PMID- 20152466
TI  - A novel low-cost and easy to develop functionalization platform. Case study:
      aptamer-based detection of thrombin by surface plasmon resonance.
AB  - A novel low-cost platform to assess biomolecular interactions was investigated
      using surface plasmon resonance and an aptamer-based assay for thrombin
      detection. Gold SPR surface functionalized with a carboxylated cross-linked BSA
      film (cBSA) and commercially available carboxymethylated dextran chip (CM5) were
      used as immobilization platforms for the thrombin binding aptamer. The high end
      commercial instrument Biacore 3000 and a custom made FIA set-up involving TI
      Spreeta sensor (TSPR2K23) were used to assess different concentrations of
      thrombin within the range 0.1-150 nM both in buffer and in a complex matrix
      (plasma) using the obtained aptasensors. Based on data derived from both CM5 and
      cBSA platforms, the cBSA aptasensor exhibited good selectivity, stability and
      regeneration ability, both in buffer and in complex matrices (plasma), comparable
      with CM5.

PMID- 20152467
TI  - Detection of refined olive oil adulteration with refined hazelnut oil by
      employing NMR spectroscopy and multivariate statistical analysis.
AB  - NMR spectroscopy was employed for the detection of adulteration of refined olive
      oil with refined hazelnut oil. Fatty acids and iodine number were determined by
      (1)H NMR, whereas (31)P NMR was used for the quantification of minor compounds
      including phenolic compounds, diacylglycerols, sterols, and free fatty acids
      (free acidity). Classification of the refined oils based on their fatty acids
      content and the concentration of their minor compounds was achieved by using the
      forward stepwise canonical discriminant analysis (CDA) and the classification
      binary trees (CBTs). Both methods provided good discrimination between the
      refined hazelnut and olive oils. Different admixtures of refined olive oils with
      refined hazelnut oils were prepared and analyzed by (1)H NMR and (31)P NMR
      spectroscopy. Subsequent application of CDA to the NMR data allowed the detection
      of the presence of refined hazelnut oils in refined olive oils at percentages
      higher than 5%. Application of the non-linear classification method of the binary
      trees offered better possibilities of measuring adulteration of the refined olive
      oils at a lower limit of detection than that obtained by the CDA method.

PMID- 20152468
TI  - Ultrasensitive Cu2+ sensing by near-infrared-emitting CdSeTe alloyed quantum
      dots.
AB  - The near-infrared (NIR)-emitting CdSeTe alloyed quantum dots (AQdots) that capped
      with L-cysteine were applied for ultrasensitive Cu(2+) sensing. The sensing
      approach was based on the fluorescence of the AQdots selectively quenched in the
      presence of Cu(2+). Experimental results showed a low interference response
      towards other metal ions. The possible quenching mechanism was discussed on the
      basis of the binding between L-cysteine and the metal ions. In addition,
      biomolecules have low effect on the fluorescence due to the minimized
      interferences in NIR region. The response of the NIR optical sensor was linearly
      proportional to the concentration of Cu(2+) ranging from 2 x 10(-8) to 2 x 10(-6)
      mol L(-1). Furthermore, it has been successfully applied to the detection of
      Cu(2+) in vegetable samples.

PMID- 20152469
TI  - Direct electrochemistry and electrocatalysis of hemoglobin on gold nanoparticle
      decorated carbon ionic liquid electrode.
AB  - In this paper a carbon ionic liquid electrode (CILE) was fabricated by using
      ionic liquid 1-ethyl-3-methylimidazolium ethylsulfate ([EMIM]EtOSO(3)) as
      modifier and further gold nanoparticles were in situ electrodeposited on the
      surface of CILE. The fabricated Au/CILE was used as a new platform for the
      immobilization of hemoglobin (Hb) with the help of a Nafion film. Electrochemical
      experimental results indicated that direct electron transfer of Hb was realized
      on the surface of Au/CILE with a pair of well-defined quasi-reversible redox
      peaks appeared. The formal peak potential (E(0)') was obtained as -0.210 V (vs.
      SCE) in pH 7.0 phosphate buffer solution (PBS), which was the characteristic of
      Hb heme Fe(III)/Fe(II) redox couple. The fabricated Nafion/Hb/Au/CILE showed
      excellent electrocatalytic activity to the reduction of trichloroacetic acid
      (TCA) and the reduction peak current was in proportional to TCA concentration in
      the range from 0.2 to 18.0 mmol/L with the detection limit as 0.16 mmol/L
      (S/N=3). The proposed electrode showed good stability and reproducibility, and it
      had the potential application as a new third-generation electrochemical
      biosensor.

PMID- 20152470
TI  - Electrochemical determination of L-Tryptophan, L-Tyrosine and L-Cysteine using
      electrospun carbon nanofibers modified electrode.
AB  - A novel and simple method for the direct and quantitative determination of L
      tryptophan (Trp), L-tyrosine (Tyr) and L-cysteine (Cys) was proposed in this
      work. Carbon nanofibers (CNFs), made by electrospinning technique, were used to
      modify carbon paste electrode (CPE) without any treatment to study the
      electrochemical behaviors of the three amino acids using cyclic voltammetry (CV)
      and constant potential amperometric method. The results demonstrated that the
      CNFs modified carbon paste electrode (CNF-CPE) exhibited high electrocatalytic
      activity and good analytical performance towards the oxidation of the three amino
      acids. The linear ranges of Trp, Tyr and Cys were 0.1-119, 0.2-107 and 0.15-64
      microM with correlation coefficients of 0.9994, 0.9985 and 0.9996, respectively.
      All the detection limits of the analytes were 0.1 mM (S/N=3). In addition, the
      CNF-CPE displayed good reproducibility, high sensitivity and good selectivity
      towards the determination of the amino acids, making it suitable for the
      determination of Trp, Tyr and Cys in clinical and medicine.

PMID- 20152471
TI  - Simultaneous determination of Fe, P, Ca, Mg, Zn, and Cu in whole blood by two-jet
      plasma atomic emission spectrometry.
AB  - Availability of many biological samples in ample quantity for biomedical
      investigations sometimes is very restricted. Therefore, there is the need for the
      simple techniques allowing the analysis of small amount samples. In the present
      work the two-jet plasma atomic emission spectrometry techniques for the
      determination of Fe, P, Ca, Mg, Zn, and Cu in whole blood are proposed. The first
      technique is developed for direct analysis of freeze-dried blood. The sample
      preparation consisted in a dilution of blood powder (particle size 20 microm or
      less) with a spectroscopic buffer (graphite powder containing 15 wt.% NaCl). For
      the analysis of liquid whole blood, previous carbonization (not ashing) of blood
      evaporated on graphite powder was applied. Calibration samples based on graphite
      powder containing 15 wt.% NaCl were used. The validation of the techniques was
      confirmed by the use of different sample preparation procedures (wet acid
      digestion and dry carbonization), the analysis of IAEA A-13 reference material
      (freeze-dried bovine whole blood), and the comparison of the results obtained by
      the proposed technique with the results of the stripping voltammetry technique.
      Just 20-50 microL of whole blood is quite enough for all determinations. The
      proposed techniques were successfully applied for the simultaneous determination
      of Fe, P, Ca, Mg, Zn, and Cu in whole blood of living experimental rats and mice
      and human blood.

PMID- 20152473
TI  - Estimation of antioxidant capacity against peroxynitrite and hypochlorite with
      fluorescein.
AB  - Peroxynitrite and hypochlorite are oxidants relevant in many pathological
      situations. We propose a simple spectrofluorometric assay to determine
      antioxidant capacity against hypochlorite and peroxynitrite based on protection
      against fluorescein bleaching. The assay can be performed on a microplate and
      requires minute amounts of material. Standard antioxidants show different
      reactivities for both oxidants. Antioxidant capacity of fruit bodies of edible
      mushrooms, tea, coffee and wine estimated as exemplary biological material point
      to considerable differences in the scavenging capacity of various biological
      material against hypochlorite, peroxynitrite and peroxyl radicals.

PMID- 20152472
TI  - Determination of Citrus aurantium protoalkaloids using HPLC with acidic potassium
      permanganate chemiluminescence detection.
AB  - Acidic potassium permanganate chemiluminescence was explored as a sensitive and
      selective mode of detection for phenolic phenethylamines (adrenergic amines) in
      consumer products containing Citrus aurantium extracts. Nine commercially
      available weight-loss products were analysed using rapid reversed-phase
      chromatography with a monolithic column (separation time of 4 min). The results
      were in good agreement with package labelling, with some notable exceptions. The
      products contained a wide concentration range of synephrine and total adrenergic
      amines, and the difference in consumer intake was even greater when the
      manufacturers' recommended daily consumption was considered. The quantity of the
      extract, often specified on the packaging as equivalent grams of dry C. aurantium
      fruit, was a poor indicator of the concentration of the active ingredients.
      Methionine, a thioether amino acid contained in some weight-loss products, was
      identified as a potential interferent for this mode of detection.

PMID- 20152474
TI  - 25 years after HIV discovery: prospects for cure and vaccine.

PMID- 20152475
TI  - HIV: a discovery opening the road to novel scientific knowledge and global health
      improvement.

PMID- 20152476
TI  - Editorial comment.

PMID- 20152477
TI  - Editorial comment.

PMID- 20152479
TI  - Editorial comment.

PMID- 20152480
TI  - Editorial comment.

PMID- 20152481
TI  - Editorial comment.

PMID- 20152482
TI  - Editorial comment.

PMID- 20152483
TI  - Editorial comment.

PMID- 20152484
TI  - Editorial comment.

PMID- 20152486
TI  - Editorial comment.

PMID- 20152487
TI  - Editorial comment.

PMID- 20152490
TI  - Editorial comment.

PMID- 20152492
TI  - Editorial comment.

PMID- 20152494
TI  - Editorial comment.

PMID- 20152495
TI  - Editorial comment.

PMID- 20152497
TI  - Editorial comment.

PMID- 20152499
TI  - Editorial comment.

PMID- 20152501
TI  - Editorial comment.

PMID- 20152503
TI  - Editorial comment.

PMID- 20152505
TI  - Editorial comment.

PMID- 20152507
TI  - Editorial comment.

PMID- 20152509
TI  - Editorial comment.

PMID- 20152510
TI  - Editorial comment.

PMID- 20152512
TI  - Strengthening accrual to cancer clinical trials.

PMID- 20152513
TI  - Dilemmas and controversies in the management of prostate cancer continue to
      present a vexing challenge to physicians and patients dealing with the disease.
      Preface.

PMID- 20152514
TI  - Prostate cancer: to screen or not to screen?
AB  - The debate about the usefulness of population-based prostate cancer screening has
      been ongoing for decades. The most current evidence shows limited benefit of
      population screening, and significant psychological, physical and financial
      costs. Efforts to improve screening with better markers and more selective
      treatment may make population-based screening more effective.

PMID- 20152515
TI  - Chemoprevention of prostate cancer.
AB  - Prostate cancer is an appropriate target for primary chemoprevention because of
      its ubiquity, disease-related mortality, treatment-related morbidity, and long
      latency period. The PCPT and REDUCE trials demonstrate that this cancer can be
      prevented by a relatively nontoxic oral pharmacologic agent (5alpha-reductase
      inhibitors). Evidence from the SELECT trial argues against the recommendation of
      the use of vitamins and micronutrients as chemoprevention of prostate cancer.
      Dietary modification may substantially alter a man's risk of prostate cancer, but
      the specific dietary manipulations that are necessary are poorly defined and
      these may need to be instituted in early adulthood to be successful. 5alpha
      reductase inhibitors represent an effective primary prevention strategy, and
      these agents should be used more liberally for the prevention of prostate cancer,
      particularly in high-risk patients.

PMID- 20152517
TI  - High-intensity focused ultrasound: ready for primetime.
AB  - Prostate cancer (CaP) is the second most common cause of cancer deaths in the
      United States and the incidence of CaP has remained constant at 165 cases per
      100,000 men. Since 1990, the age-adjusted death rate has decreased by 31%. In
      this article, the authors review the current literature on the experimental
      therapy for HIFU. The HIFU technique, its mechanism of action, patient selection,
      current efficacy studies, complications, follow-up after HIFU treatment, and
      future developments are discussed.

PMID- 20152518
TI  - Overcoming the learning curve for robotic-assisted laparoscopic radical
      prostatectomy.
AB  - Robotic-assisted laparoscopic radical prostatectomy (RALP) has been rapidly
      adopted in the last few years despite having a prolonged learning curve. This
      article describes the RALP learning curve, reviews in detail the challenging
      steps of the operation, describes the authors' RALP technique, and concludes with
      tips to overcome the learning curve.

PMID- 20152516
TI  - Update on prostate imaging.
AB  - Successful and accurate imaging of prostate cancer is integral to its clinical
      management from detection and staging to subsequent monitoring. Various
      modalities are used including ultrasound, computed tomography, and magnetic
      resonance imaging, with the greatest advances seen in the field of magnetic
      resonance.

PMID- 20152519
TI  - The case for open radical prostatectomy.
AB  - Radical prostatectomy is the gold standard surgical treatment for clinically
      localized prostate cancer. Over the years, many different approaches to surgical
      removal of the prostate have been described. Today, the most common techniques
      are open radical retropubic prostatectomy and robotic-assisted laparoscopic
      radical prostatectomy. Although there are many differences between the 2
      approaches, the common goal is to optimize oncologic and functional outcomes.
      This article highlights the background, techniques, and outcomes of open and
      robotic prostatectomy.

PMID- 20152520
TI  - Controversies surrounding lymph node dissection for prostate cancer.
AB  - Despite the high frequency with which radical prostatectomy is used to treat
      prostate cancer, uncertainty exists regarding the merits of a simultaneous pelvic
      lymph node dissection. Unresolved issues include identifying the optimal
      candidate and selecting the appropriate surgical template, among others. In this
      article, the authors discuss the pros and cons of performing a pelvic lymph node
      dissection and the staging/diagnostic and therapeutic implications of this
      procedure. The lack of robust randomized clinical trials in the literature
      necessitates a careful analysis of retrospective and case series data.

PMID- 20152521
TI  - Primary and salvage cryotherapy for prostate cancer.
AB  - Cryotherapy is a technique to ablate tissue by local induction of extremely cold
      temperatures. Recently, the American Urological Association Best Practice
      Statement recognized cryoablation of the prostate as an established treatment
      option for men with newly diagnosed or radiorecurrent organ-confined prostate
      cancer. Emerging data suggest that, in select cases, cryoablation may have a role
      in focal ablation of prostate. The current state of the art of cryoablation in
      these applications is reviewed.

PMID- 20152522
TI  - Current topics in the treatment of prostate cancer with low-dose-rate
      brachytherapy.
AB  - The treatment of prostate cancer with low dose rate prostate brachytherapy has
      grown rapidly in the last 20 years. Outcome analyses performed in this period
      have enriched understanding of this modality. This article focuses on the
      development of a real-time ultrasound-guided implant technique, the importance of
      radiation dose, trimodality treatment of high-risk disease, long-term treatment
      outcomes, and treatment-associated morbidity.

PMID- 20152523
TI  - Neoadjuvant and adjuvant therapies in prostate cancer.
AB  - Prostate cancer is the most common cancer in men in the United States and the
      second leading cause of cancer death. Advances in surgical therapies have
      paralleled advances in radiation therapy and chemotherapy for metastatic disease.
      There is a great interest in neoadjuvant and adjuvant therapies for patients at
      intermediate and high risk of recurrence and prostate cancer-specific death.
      Because high-risk prostate cancer patients can be readily identified by clinical
      criteria, many studies have attempted to use local and systemic adjuvant therapy
      to reduce the risk of recurrence. This review discusses neoadjuvant and adjuvant
      therapies in prostate cancer, including hormonal therapy, chemotherapy, and
      postoperative radiotherapy.

PMID- 20152524
TI  - Novel targeted therapies for prostate cancer.
AB  - This article reviews the concepts and rationale behind targeted agents that are
      currently in clinical testing for patients with castration resistant prostate
      cancer (CRPC). Advances in our understanding of the molecular mechanisms
      underlying prostate cancer progression has translated into a variety of treatment
      approaches. Agents targeting androgen receptor activation and local
      steroidogenesis, angiogenesis, apoptosis, chaperone proteins, the insulinlike
      growth factor pathway, RANK ligand, endothelin receptors, and Src family kinases
      are entering, or have recently completed, accrual to phase III trials for
      patients with CRPC. There has also been interest generated by data from early
      phase studies evaluating multitargeted tyrosine kinase inhibitors, agents
      effecting signal transduction pathways, and novel cytotoxics.

PMID- 20152525
TI  - Immunotherapy for prostate cancer: an emerging treatment modality.
AB  - This article examines prostate cancer as a target for immunotherapy and
      investigates active immunotherapy for prostate cancer, combining conventional
      therapy with active immunotherapy, immune modulators (brakes and accelerators),
      and monoclonal antibodies.

PMID- 20152527
TI  - Fabricated or induced illness by carers: a complex conundrum.

PMID- 20152528
TI  - Mental illness in Australian immigration detention centres.

PMID- 20152526
TI  - Blood and tissue biomarkers in prostate cancer: state of the art.
AB  - The prevalence of prostate cancer (PCa) is high and increases with age. PCa is
      the most common cutaneous cancer in American men. Prostate-specific antigen (PSA)
      screening has impacted the detection of PCa and is directly responsible for a
      dramatic decrease in stage at diagnosis. Gleason score and stage at the time of
      diagnosis remain the mainstay to predict prognosis, in the absence of more
      accurate and reliable tissue or blood biomarkers. Despite extensive research
      efforts, very few biomarkers of PCa have been introduced to date in clinical
      practice. Even screening with PSA has recently been questioned. A thorough
      analysis of all tissue and serum biomarkers in prostate cancer research cannot be
      easily synthesized, and goes beyond the scope of the present article. Therefore
      the authors focus here on the most recently reported tissue and circulating
      biomarkers for PCa whose application in clinical practice is either current or
      expected in the near future.

PMID- 20152529
TI  - Guidance on prevention of venous thromboembolism.

PMID- 20152530
TI  - Organ transplantation between HIV-infected patients.

PMID- 20152531
TI  - Offline: Speaking up, loudly.

PMID- 20152532
TI  - Tony Mok: leading light in Hong Kong oncology.

PMID- 20152533
TI  - Community-based interventions to reduce maternal mortality.

PMID- 20152534
TI  - Community-based interventions to reduce maternal mortality.

PMID- 20152535
TI  - Community-based interventions to reduce maternal mortality.

PMID- 20152537
TI  - Community-based interventions to reduce maternal mortality.

PMID- 20152538
TI  - Empowering women to control post-partum haemorrhage.

PMID- 20152539
TI  - Preventable deaths in sickle-cell anaemia in African children.

PMID- 20152540
TI  - Preventable deaths in sickle-cell anaemia in African children.

PMID- 20152541
TI  - Reducing prescription errors.

PMID- 20152543
TI  - Reducing prescription errors.

PMID- 20152544
TI  - Reducing prescription errors.

PMID- 20152545
TI  - A life-threatening sore throat masquerading as swine flu.

PMID- 20152547
TI  - Antiplatelet agents in acute coronary syndromes.
AB  - The platelet plays an essential role in atherothrombosis. Clinically, platelet
      rich thrombi underlie acute coronary syndromes (ACSs). Current therapies have
      improved outcomes, however, often at the expense of increased risk of bleeding.
      With the increase in our understanding of the underlying pathophysiology of ACSs,
      newer targets for antiplatelet therapies continue to emerge. Novel antiplatelet
      agents may provide even greater reductions in ischemic events with the potential
      for less bleeding. This article reviews the evidence for current antiplatelet
      agents in ACSs as well as for the newer agents in later phases of clinical
      testing.

PMID- 20152548
TI  - The role of aripiprazole in Canada: A review of clinical and drug discontinuation
      data. Foreword.

PMID- 20152549
TI  - Patterns of discontinuation of atypical antipsychotics in the province of Quebec:
      A retrospective prescription claims database analysis.
AB  - BACKGROUND: Patterns of discontinuation of atypical antipsychotic drugs,
      including the return to therapy after an interruption, have not been examined
      longitudinally. OBJECTIVE: This study was conducted to describe discontinuation
      patterns of atypical antipsychotic drugs across a spectrum of outpatients in the
      province of Quebec. METHODS: This retrospective, inception cohort study employed
      data from the Quebec health insurance board databases and the Quebec
      hospitalization registry on Quebec Drug Plan beneficiaries between the ages of 20
      and 64 years who first filled a prescription for any antipsychotic drug between
      January 1, 2000, and December 31, 2007. Five subcohorts were constructed
      according to the initial antipsychotic received: either 1 of the 4 atypical
      antipsychotics covered by the Quebec drug plan at the time of the study
      olanzapine, quetiapine, risperidone, and clozapine-or polytherapy (>1 atypical
      antipsychotic, or 1 atypical and 1 typical antipsychotic). Discontinuation was
      defined as a failure to refill the initial prescription within 2 times the days'
      supply of the preceding claim. In individuals who discontinued initial drug
      treatment, a new course of treatment was defined as initiation of treatment with
      any antipsychotic drug after a first treatment discontinuation. Discontinuation
      of a second course of treatment was defined as failure to refill a prescription
      for the second drug within 2 times the days' supply of the preceding claim.
      Patients were followed from initiation to December 31, 2004, ineligibility for
      the drug plan, or death, whichever came first. Kaplan-Meier curves and Cox
      regression models were used to compare discontinuations and new courses of
      treatment by initial atypical antipsychotic. RESULTS: The overall cohort
      consisted of 46,074 drug plan beneficiaries who had initiated antipsychotic
      treatment during the specified period. The majority of individuals were female
      (54.6%) and lived in urban areas (79.2%); the median age ranged from 40 to 44
      years. The mean (SD) duration of follow-up was 2.67 (1.91) years. Compared with
      individuals whose initial therapy was olanzapine, those whose initial therapy was
      quetiapine had a significantly higher likelihood of discontinuing initial
      treatment (adjusted hazard ratio [AHR] = 1.06; 95% CI, 1.04-1.09; P < 0.001). The
      likelihood of discontinuing initial treatment was significantly lower among those
      whose initial therapy was risperidone (AHR = 0.93; 95% CI, 0.90-0.95; P < 0.001),
      clozapine (AHR = 0.56; 95% CI, 0.46-0.68; P < 0.001), or polytherapy (AHR = 0.69;
      95% CI, 0.64-0.74; P < 0.001). Those whose initial therapy was quetiapine were
      significantly less likely than those whose initial therapy was olanzapine to
      begin a second course of treatment (AHR = 0.95; 95% CI, 0.90-0.99; P = 0.02).
      Compared with individuals who initiated a second course of treatment with
      olanzapine, those who initiated a second course with quetiapine were more likely
      to discontinue again (AHR = 1.09; 95% CI, 1.04-1.14; P < 0.001), whereas those
      who initiated a second course with risperidone were less likely to discontinue
      again (AHR = 0.95; 95% CI, 0.90-1.00; P = 0.04). CONCLUSIONS: This study
      population had a high risk of discontinuing initial atypical antipsychotic
      therapy within 1 year. Those who discontinued had a low likelihood of returning
      to treatment, and those who did return to treatment had a high likelihood of
      discontinuing again. These patterns of use may have serious consequences for
      patients' health and for the utilization of health services.

PMID- 20152550
TI  - Aripiprazole in schizophrenia and schizoaffective disorder: A review.
AB  - BACKGROUND: During the past decade, there has been some progress in the
      pharmacotherapy of schizophrenia and schizoaffective disorder. Current evidence
      supports the use of various second-generation, or atypical, antipsychotic
      medications, although few of these agents have been associated with long-term
      efficacy and tolerability. Aripiprazole is an atypical antipsychotic that has
      been found to improve positive and negative symptoms of schizophrenia with a
      favorable adverse-effect profile. OBJECTIVE: This article reviews the efficacy
      and tolerability of aripiprazole in the context of recommended management
      strategies for schizophrenia and schizoaffective disorder, and in comparison with
      first-generation and other second-generation antipsychotics. METHODS: A search of
      MEDLINE (1999-May 2009) was conducted for reports of short- and long-term
      clinical studies of atypical antipsychotics (including aripiprazole) and meta
      analyses of randomized controlled trials comparing first- and second-generation
      antipsychotics (including aripiprazole) in the treatment of schizophrenia or
      schizoaffective disorder. The search terms were schizophrenia; schizoaffective
      disorder; pharmacogenetics; adverse effects; tardive dyskinesia AND atypical
      antipsychotics; aripiprazole; aripiprazole, schizophrenia, AND double-blind
      studies; and atypical antipsychotics AND adverse effects. The reference lists of
      identified articles were reviewed for additional relevant publications. Only full
      study publications were included. RESULTS: Based on the clinical evidence,
      including data from short-term (4-8 weeks) and long-term (26-52 weeks)
      randomized, double-blind clinical trials, aripiprazole has been associated with
      improvements in positive, negative, cognitive, and affective symptoms of
      schizophrenia and schizoaffective disorder. It has been associated with long-term
      (up to 52 weeks) symptom control in schizophrenia, as well as with efficacy in
      treatment-resistant schizophrenia. Common adverse effects associated with
      aripiprazole were nausea, insomnia, and agitation. These effects were usually
      transient. The evidence suggests that aripiprazole is unlikely to be associated
      with clinically significant weight gain or dyslipidemia, increased prolactin
      levels, or prolongation of the QTc interval. Compared with placebo, aripiprazole
      has been reported to have a relatively low potential for inducing metabolic
      syndrome. CONCLUSIONS: Based on the evidence reviewed, aripiprazole monotherapy
      appears to be effective and well tolerated in treating the positive, negative,
      and cognitive symptoms of schizophrenia and schizoaffective disorder. It was
      associated with a low risk for the common adverse effects of antipsychotic
      therapy, including metabolic and endocrine alterations.

PMID- 20152551
TI  - Aripiprazole for the maintenance treatment of bipolar I disorder: A review.
AB  - BACKGROUND: Bipolar disorder is a chronic neuropsychiatric syndrome associated
      with substantial rates of recurrence, interepisodic dysfunction, comorbidity, and
      premature mortality. Metabolic comorbidity (eg, overweight, obesity, metabolic
      syndrome) differentially affects individuals with bipolar disorder and
      contributes to increased illness-associated morbidity and mortality (ie,
      cardiovascular disease). Few pharmacologic agents have been approved by the US
      Food and Drug Administration for the maintenance treatment of bipolar disorder.
      OBJECTIVE: This paper discusses the metabolic profile of aripiprazole and reviews
      pivotal registration trials of aripiprazole for the maintenance treatment of
      adults with bipolar I disorder. METHODS: MEDLINE was searched for English
      language articles published between January 1995 and November 2009. The key
      search term was aripiprazole, combined with bipolar disorder and maintenance
      treatment. The review was limited to randomized, controlled registration trials,
      supplemented by poster presentations involving the registration-trial data sets.
      RESULTS: Three studies of the efficacy and tolerability of aripiprazole
      monotherapy in the maintenance treatment of bipolar I disorder were identified by
      the literature search: a 26-week, randomized, double-blind study and its 74-week
      extension phase (for a total of 100 weeks of double-blind treatment), and a
      randomized, double-blind comparison of aripiprazole with placebo and lithium
      (internal comparator) for up to 12 weeks. After 100 weeks of double-blind
      treatment, aripiprazole had a minimal effect on body composition and did not
      disrupt metabolic parameters compared with placebo. The mean (SD) weight change
      was 0.4 (0.8) kg with aripiprazole and -1.9 (0.8) kg with placebo (P = NS). A
      clinically significant (> or =7%) increase in weight occurred in 20% of the
      aripiprazole group and 5% of the placebo group (P = 0.01). Extrapyramidal
      symptoms were reported in 22% of the aripiprazole group and 15% of the placebo
      group. The identified trials of aripiprazole primarily enrolled patients during a
      manic state; no maintenance trials of combination therapy or trials enrolling
      individuals presenting with an acute depressive episode were identified.
      CONCLUSIONS: The available evidence supports the efficacy and tolerability of
      aripiprazole in the maintenance treatment of bipolar disorder. The placebo
      subtracted differences in body composition and metabolic parameters suggest
      utility for aripiprazole in the long-term treatment of bipolar disorder.

PMID- 20152553
TI  - VACCINE in the 21st century: what's next?

PMID- 20152552
TI  - GARS axonopathy: not every neuron's cup of tRNA.
AB  - Charcot-Marie-Tooth disease type 2D, a hereditary axonal neuropathy, is caused by
      mutations in glycyl-tRNA synthetase (GARS). The mutations are distributed
      throughout the protein in multiple functional domains. In biochemical and cell
      culture experiments, some mutant forms of GARS have been indistinguishable from
      wild-type protein, suggesting that these in vitro tests might not adequately
      assess the aberrant activity responsible for axonal degeneration. Recently, mouse
      and fly models have offered new insights into the disease mechanism. There are
      still gaps in our understanding of how mutations in a ubiquitously expressed
      component of the translation machinery result in axonal neuropathy. Here, we
      review recent reports, weigh the evidence for and against possible mechanisms and
      suggest areas of focus for future work.

PMID- 20152554
TI  - [Tobacco and pregnancy: France always bad pupil].

PMID- 20152555
TI  - An unusual case of pericardial effusion in a diabetic patient.

PMID- 20152556
TI  - Use of herbal products and potential interactions in patients with cardiovascular
      diseases.
AB  - More than 15 million people in the U.S. consume herbal remedies or high-dose
      vitamins. The number of visits to providers of complementary and alternative
      medicine exceeds those to primary care physicians, for annual out-of-pocket costs
      of $30 billion. Use of herbal products forms the bulk of treatments, particularly
      by elderly people who also consume multiple prescription medications for comorbid
      conditions, which increases the risk of adverse herb-drug-disease interactions.
      Despite the paucity of scientific evidence supporting the safety or efficacy of
      herbal products, their widespread promotion in the popular media and the
      unsubstantiated health care claims about their efficacy drive consumer demand. In
      this review, we highlight commonly used herbs and their interactions with
      cardiovascular drugs. We also discuss health-related issues of herbal products
      and suggest ways to improve their safety to better protect the public from
      untoward effects.

PMID- 20152557
TI  - Treatment of heart failure with normal ejection fraction: an inconvenient truth!
AB  - Despite use of similar drugs, outcomes of recent heart failure (HF) trials were
      frequently neutral in heart failure with normal left ventricular ejection
      fraction (HFNEF) and positive in heart failure with reduced left ventricular
      ejection fraction (HFREF). The neutral outcomes of HFNEF trials were often
      attributed to deficient HFNEF patient recruitment with inclusion of many HFREF or
      noncardiac patients. Patient recruitment criteria of 21 HFNEF trials were
      therefore reviewed in reference to diagnostic guidelines for HFNEF. In the 4
      published sets of guidelines, a definite diagnosis of HFNEF required the
      simultaneous and obligatory presence of signs and/or symptoms of HF and evidence
      of normal systolic left ventricular (LV) function and of diastolic LV
      dysfunction. In 3 of 4 sets of guidelines, normal systolic LV function comprised
      both a left ventricular ejection fraction (LVEF) >50% and an absence of LV
      dilation. Among the 21 HFNEF trials, LVEF cutoff values ranged from 35% to 50%,
      with only 8 trials adhering to an LVEF >50%. Furthermore, only 1 trial specified
      a normal LV end-diastolic dimension as an enrollment criterion and only 7 trials
      required evidence of diastolic LV dysfunction. Nonadherence to diagnostic
      guidelines induced excessive enrollment into HFNEF trials of HF patients with
      eccentric LV remodeling and ischemic heart disease compared with HF patients with
      concentric LV remodeling and arterial hypertension. Nonadherence to guidelines
      also led to underpowered HFNEF trials with a low incidence of outcome events such
      as death or HF hospitalizations. Future HFNEF trials should therefore adhere to
      diagnostic guidelines for HFNEF.

PMID- 20152558
TI  - Endovascular stenting for vertebral artery stenosis.
AB  - OBJECTIVES: The aim of this study was to demonstrate the safety and long-term
      durability of catheter-based therapy for symptomatic vertebral artery stenosis
      (VAS). BACKGROUND: Symptomatic VAS carries with it a 5-year 30% to 35% risk of
      stroke. The 2-year mortality approaches 30% for medically managed strokes
      involving the posterior circulation. Surgical bypass is rarely performed, due to
      high morbidity and mortality. Endovascular revascularization with primary
      stenting offers an attractive treatment option for these patients. METHODS: One
      hundred five consecutive symptomatic patients (112 arteries, 71% male) underwent
      stent placement for extracranial (91%) and intracranial (9%) VAS from 1995 to
      2006. Fifty-seven patients (54%) had bilateral VAS, 71 patients (68%) had
      concomitant carotid disease, and 43 patients (41%) had a prior stroke. RESULTS:
      Procedural and clinical success was achieved in 105 (100%) and 95 (90.5%)
      patients, respectively. One-year follow-up was obtained in 87 (82.9%) patients,
      of which 69 patients (79.3%) remained symptom-free. At 1 year, 6 patients (5.7%)
      had died and 5 patients (5%) had a posterior circulation stroke. Target vessel
      revascularization occurred in 7.4% at 1 year. At a median follow-up of 29.1
      months (interquartile range 12.8 to 50.9 months), 13.1% underwent target vessel
      revascularization, 71.4% were alive, and 70.5% remained symptom-free.
      CONCLUSIONS: In experienced hands, stenting for symptomatic VAS can be
      accomplished with a very high success rate (100%), with few periprocedural
      complications, and is associated with durable symptom resolution in the majority
      (approximately 80%) of patients. We conclude that endovascular stenting of
      vertebral artery atherosclerotic disease is safe and effective compared with
      surgical controls and should be considered first-line therapy for this disease.

PMID- 20152559
TI  - A randomized comparison of the Endeavor zotarolimus-eluting stent versus the
      TAXUS paclitaxel-eluting stent in de novo native coronary lesions 12-month
      outcomes from the ENDEAVOR IV trial.
AB  - OBJECTIVES: The ENDEAVOR IV (Randomized Comparison of Zotarolimus-Eluting and
      Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) trial
      evaluated the safety and efficacy of the zotarolimus-eluting stent (ZES) compared
      with the paclitaxel-eluting stent (PES). BACKGROUND: First-generation drug
      eluting stents have reduced angiographic and clinical restenosis, but long-term
      safety remains controversial. A second-generation drug-eluting stent, which
      delivers zotarolimus, a potent antiproliferative agent, via a biocompatible
      phosphorylcholine polymer on a cobalt alloy thin-strut stent has shown promising
      experimental and early clinical results. METHODS: This is a prospective,
      randomized (1:1), single-blind, controlled trial comparing outcomes of patients
      with single de novo coronary lesions treated with ZES or PES. The primary end
      point was noninferiority of 9-month target vessel failure defined as cardiac
      death, myocardial infarction, or target vessel revascularization. RESULTS: Among
      a total of 1,548 patients assigned to ZES (n = 773) or PES (n = 775), at 9
      months, ZES was noninferior to PES with rates of target vessel failure 6.6%
      versus 7.1%, respectively (p(noninferiority) < or = 0.001). There were fewer
      periprocedural myocardial infarctions with ZES (0.5% vs. 2.2%; p = 0.007),
      whereas at 12 months, there were no significant differences between groups in
      rates of cardiac death, myocardial infarction, target vessel revascularization,
      or stent thrombosis. Although incidence of 8-month binary angiographic in-segment
      restenosis was higher in patients treated with ZES versus PES (15.3% vs. 10.4%; p
      = 0.284), rates of 12-month target lesion revascularization were similar (4.5%
      vs. 3.2%; p = 0.228), especially in patients without planned angiographic follow
      up (3.6% vs. 3.2%; p = 0.756). CONCLUSIONS: These findings demonstrate that ZES
      has similar clinical safety and efficacy compared with PES in simple and medium
      complexity single de novo coronary lesions. (ENDEAVOR IV Clinical Trial;
      NCT00217269).

PMID- 20152560
TI  - When can noninferior be superior? The multidimensional nature of clinical
      decision-making calls for innovative approaches to clinical trials.

PMID- 20152561
TI  - A double-blind, randomized study on prevention and existence of a rebound
      phenomenon of platelets after cessation of clopidogrel treatment.
AB  - OBJECTIVES: The goal of this study was to assess whether a platelet rebound
      exists and whether it can be attenuated by clopidogrel tapering. BACKGROUND:
      Clinical studies have reported a clustering of thrombotic events after stopping
      clopidogrel treatment. The hypothesis of a rebound phenomenon of platelets has
      been declared causative, but its existence has never been confirmed. Tapering of
      clopidogrel over a certain period of time before stopping the drug completely
      might provide a way to attenuate this supposed phenomenon. METHODS: Patients (n =
      69) receiving clopidogrel treatment due to prior drug-eluting stent placement and
      planning to stop clopidogrel were recruited in a double-blind, randomized trial.
      Patients were randomized to either receive a pre-specified tapering regimen
      (tapering group; n = 35) for 4 weeks with complete discontinuation of clopidogrel
      thereafter or continue a daily clopidogrel intake for 4 more weeks with abrupt
      discontinuation afterwards (off group; n = 34). Platelet aggregation (PA) was
      assessed with light transmission aggregometry (LTA) and multiple electrode
      aggregometry (MEA) simultaneously at study inclusion and at weeks 2 to 8 after
      randomization. The primary end point was the highest value of adenosine
      diphosphate-induced PA measured with LTA in the weeks after complete cessation of
      clopidogrel in both groups. RESULTS: The highest values of adenosine diphosphate
      induced PA after complete cessation of clopidogrel were similar between both
      groups (p = 0.21 with LTA, and p = 0.55 with MEA). CONCLUSIONS: Tapering of
      clopidogrel does not result in lower PA values after clopidogrel withdrawal. The
      course of PA values after clopidogrel cessation provides no evidence for the
      existence of a rebound phenomenon of platelets.

PMID- 20152562
TI  - Lead extraction in the contemporary setting: the LExICon study: an observational
      retrospective study of consecutive laser lead extractions.
AB  - OBJECTIVES: This study sought to examine the safety and efficacy of laser
      assisted lead extraction and the indications, outcomes, and risk factors in a
      large series of consecutive patients. BACKGROUND: The need for lead extraction
      has been increasing in direct relationship to the increased numbers of
      cardiovascular implantable electronic devices. METHODS: Consecutive patients
      undergoing transvenous laser-assisted lead extraction at 13 centers were
      included. RESULTS: Between January 2004 and December 2007, 1,449 consecutive
      patients underwent laser-assisted lead extraction of 2,405 leads (20 to 270
      procedures/site). Median implantation duration was 82.1 months (0.4 to 356.8
      months). Leads were completely removed 96.5% of the time, with a 97.7% clinical
      success rate whereby clinical goals associated with the indication for lead
      removal were achieved. Failure to achieve clinical success was associated with
      body mass index <25 kg/m(2) and low extraction volume centers. Procedural failure
      was higher in leads implanted for >10 years and when performed in low volume
      centers. Major adverse events in 20 patients were directly related to the
      procedure (1.4%) including 4 deaths (0.28%). Major adverse effects were
      associated with patients with a body mass index <25 kg/m(2). Overall all-cause in
      hospital mortality was 1.86%; 4.3% when associated with endocarditis, 7.9% when
      associated with endocarditis and diabetes, and 12.4% when associated with
      endocarditis and creatinine > or =2.0. Indicators of all-cause in-hospital
      mortality were pocket infections, device-related endocarditis, diabetes, and
      creatinine > or =2.0. CONCLUSIONS: Lead extraction employing laser sheaths is
      highly successful with a low procedural complication rate. Total mortality is
      substantially increased with pocket infections or device-related endocarditis,
      particularly in the setting of diabetes, renal insufficiency, or body mass index
      <25 kg/m(2). Centers with smaller case volumes tended to have a lower rate of
      successful extraction.

PMID- 20152563
TI  - Compound and digenic heterozygosity contributes to arrhythmogenic right
      ventricular cardiomyopathy.
AB  - OBJECTIVES: The aim of this study was to define the genetic basis of
      arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND:
      Arrhythmogenic right ventricular cardiomyopathy, characterized by right
      ventricular fibrofatty replacement and arrhythmias, causes sudden death.
      Autosomal dominant inheritance, reduced penetrance, and 7 desmosome-encoding
      causative genes are known. The basis of low penetrance is poorly understood.
      METHODS: Arrhythmogenic right ventricular cardiomyopathy probands and family
      members were enrolled, blood was obtained, lymphoblastoid cell lines were
      immortalized, deoxyribonucleic acid was extracted, polymerase chain reaction
      (PCR) amplification of desmosome-encoding genes was performed, PCR products were
      sequenced, and diseased tissue samples were studied for intercellular junction
      protein distribution with confocal immunofluorescence microscopy and antibodies
      against key proteins. RESULTS: We identified 21 variants in plakophilin-2 (PKP2)
      in 38 of 198 probands (19%), including missense, nonsense, splice site, and
      deletion/insertion mutations. Pedigrees showed wide intra-familial variability
      (severe early-onset disease to asymptomatic individuals). In 9 of 38 probands,
      PKP2 variants were identified that were encoded in trans (compound
      heterozygosity). The 38 probands hosting PKP2 variants were screened for other
      desmosomal genes mutations; second variants (digenic heterozygosity) were
      identified in 16 of 38 subjects with PKP2 variants (42%), including desmoplakin
      (DSP) (n = 6), desmoglein-2 (DSG2) (n = 5), plakophilin-4 (PKP4) (n = 1), and
      desmocollin-2 (DSC2) (n = 1). Heterozygous mutations in non-PKP 2 desmosomal
      genes occurred in 14 of 198 subjects (7%), including DSP (n = 4), DSG2 (n = 5),
      DSC2 (n = 3), and junctional plakoglobin (JUP) (n = 2). All variants occurred in
      conserved regions; none was identified in 700 ethnic-matched control subjects.
      Immunohistochemical analysis demonstrated abnormalities of protein architecture.
      CONCLUSIONS: These data suggest that the genetic basis of ARVC includes reduced
      penetrance with compound and digenic heterozygosity. Disturbed junctional
      cytoarchitecture in subjects with desmosomal mutations confirms that ARVC is a
      disease of the desmosome and cell junction.

PMID- 20152565
TI  - Blunt traumatic aortic transection.

PMID- 20152564
TI  - Evaluation of cuff-induced ischemia in the lower extremity by magnetic resonance
      oximetry.
AB  - OBJECTIVES: The aim of this study was to evaluate vascular function in the lower
      extremities by making direct time-course measurement of oxygen saturation in the
      femoral/popliteal arteries and veins during cuff-induced reactive hyperemia with
      magnetic resonance imaging-based oximetry. BACKGROUND: Magnetic resonance imaging
      based oximetry is a new calibration-free technique taking advantage of the
      paramagnetic nature of blood that depends on the volume fraction of
      deoxyhemoglobin in red blood cells. METHODS: We compared post-occlusive blood
      oxygenation time-course of femoral/popliteal vessels in: 1) young healthy
      subjects (YH) (n = 10; mean ankle-brachial index [ABI] 1.0 +/- 0.1, mean age 30
      +/- 7 years); 2) peripheral arterial disease (PAD) patients (n = 12; mean ABI 0.6
      +/- 0.1, mean age 71 +/- 9 years); and 3) age-matched healthy control subjects
      (AHC) (n = 8; mean ABI 1.1 +/- 0.1, mean age 68 +/- 9 years). Blood oxygenation
      was quantified at 3.0-T field strength with a field mapping pulse sequence
      yielding the magnetic susceptibility difference between blood in the vessels and
      surrounding muscle tissue from which the intravascular blood oxygen saturation is
      computed as %HbO(2). RESULTS: Significantly longer washout time (42 +/- 16 s vs.
      14 +/- 4 s; p < 0.0001) and lower upslope (0.60 +/- 0.20 %HbO(2)/s vs. 1.32 +/-
      0.41 %HbO(2)/s; p = 0.0008) were observed for PAD patients compared with healthy
      subjects (YH and AHC combined). Furthermore, greater overshoot was observed in YH
      than in AHC (21 +/- 8 %HbO(2) vs. 10 +/- 5 %HbO(2); p = 0.0116). CONCLUSIONS:
      Post-occlusive transient changes in venous blood oxygenation might provide a new
      measure of vascular competence, which was found to be reduced in subjects with
      abnormal ABI, manifesting in prolonged recovery during the early phase of
      hyperemia.

PMID- 20152567
TI  - Have we really come to understand the relationship between the left ventricular
      outflow tract gradient and left ventricular emptying in hypertrophic
      cardiomyopathy?

PMID- 20152568
TI  - Determinants of functional capacity in peripheral arterial disease.

PMID- 20152571
TI  - Microvascular angina or "vis a tergo".

PMID- 20152572
TI  - The tremendous progress in QOL science in the past 20 years.

PMID- 20152573
TI  - Advances in measuring quality-of-life outcomes in cancer care.
AB  - OBJECTIVE: To provide practical guidance for the selection and use of quality-of
      life (QOL) instruments for research and clinical practice. DATA SOURCES:
      Published articles, books, and web resources. CONCLUSION: Even among instruments
      designed specifically to measure QOIL, there are vast differences in what they
      actually measure. The choice of instrument can make the difference between
      whether real changes in QOL are captured or not. IMPLICATIONS FOR NURSING
      PRACTICE: QOL outcomes are ideal for determining the efficacy and impact of
      cancer care. Incorporating QOL into standard clinical practice holds great
      promise for improving communication with health care providers, with a resultant
      improvement in patient outcomes.

PMID- 20152574
TI  - Quality of life assessments in clinical practice.
AB  - OBJECTIVES: To provide information about the value of quality of life (QOL)
      assessments to improve clinical care. DATA SOURCES: Published articles, web
      resources, clinical practice. CONCLUSION: Clinical assessment of QOL can lead to
      improved patient outcomes and provide a means of evaluating the effectiveness of
      interventions. IMPLICATIONS FOR NURSING PRACTICE: QOL assessment provides nurses
      with a more holistic view of the patient and improves communication between the
      patient and health care providers.

PMID- 20152575
TI  - Progress in quality of life in children and adolescents with cancer.
AB  - OBJECTIVES: To describe the notable progress in conceptualizing, defining, and
      measuring quality of life (QOL) in children and adolescents with cancer during
      the past two decades. DATA SOURCES: Published articles. CONCLUSION: QOL in
      children and adolescents with cancer has been defined and conceptual frameworks
      developed; multiple generic and cancer-specific instruments have been validated
      for use in this patient population. Advances include a shift to patient reports
      as the preferred source of QOL ratings, and use of multiple data collection
      points in the same study to better document the trajectory of QOL in children and
      adolescents with cancer. IMPLICATIONS FOR NURSING PRACTICE: This progress makes
      possible the study of interventions designed to improve the QOL of these young
      patients during and following treatment.

PMID- 20152576
TI  - Advances in quality of life at the end of life.
AB  - OBJECTIVES: To provide an overview of the developments in promoting quality of
      life (QOL) at the end of life (EOL) in oncology settings, to describe
      implications for clinical care for cancer patients at the EOL, and to address the
      continuing challenges for assessing QOL at the EOL. DATA SOURCES: Published
      articles, clinical guidelines, and web resources. CONCLUSION: QOL continues to be
      an important aspect of patient care at the EOL. Nursing has made substantial
      contributions to the literature on QOL at the EOL through instrument development,
      clinical care priorities, and research. IMPLICATIONS FOR NURSING PRACTICE:
      Oncology nurses practicing in clinical and research settings must be aware of the
      importance of QOL assessment for terminally ill cancer patients, be informed
      about the process of selecting relevant QOL measures for the EOL, and apply
      current knowledge to quality cancer care.

PMID- 20152577
TI  - Quality of life in cancer survivorship: 20 years later.
AB  - OBJECTIVES: To discuss the unique quality-of-life (QOL) issues for cancer
      survivors and provide guidance for the selection of measures to assess them. DATA
      SOURCES: Literature review, PubMed search, electronic data, websites. CONCLUSION:
      QOL is a vital outcome for cancer survivors. QOL measurement of the unique needs
      of cancer survivors has increased over the past 20 years. IMPLICATIONS FOR
      NURSING PRACTICE: Oncology nurses can move QOL science in cancer survivorship
      forward by using research findings to implement evidence-based practice.

PMID- 20152578
TI  - Technology and quality of life outcomes.
AB  - OBJECTIVES: To discuss recent technological advances in quality of life (QOL)
      data collection and guidance for use in research and clinical practice. The use
      of telephone-, computer-, and web/internet-based technologies to collect QOL
      data, reliability and validity issues, and cost will be discussed, along with the
      potential pitfalls associated with these technologies. DATA SOURCES: Health care
      literature and web resources. CONCLUSION: Technology has provided researchers and
      clinicians with an opportunity to collect QOL data from patients that were
      previously not accessible. Most technologies offer a variety of options, such as
      language choice, formatting options for the delivery of questions, and data
      management services. Choosing the appropriate technology for use in research
      and/or clinical practice primarily depends on the purpose for QOL data
      collection. IMPLICATIONS FOR NURSING PRACTICE: Technology is changing the way
      nurses assess QOL in patients with cancer and provide care. As stakeholders in
      the health care delivery system and patient advocates, nurses must be intimately
      involved in the evaluation and use of new technologies that impact QOL and/or the
      delivery of care.

PMID- 20152579
TI  - Health-related quality of life and culture.
AB  - OBJECTIVE: To clarify the relationship between quality of life (QOL) and culture.
      DATA SOURCE: Journal articles, proceedings, and clinical experience. CONCLUSION:
      QOL is a subjective, multidimensional experience of well-being that is culturally
      constructed as individuals seek safety and security, a sense of integrity and
      meaning in life, and a sense of belonging in one's social network. IMPLICATIONS
      FOR NURSING PRACTICE: In a society where health disparities between diverse
      groups are known to exist, it is incumbent upon nurses to consider the impact of
      ethnicity/culture on the health care they deliver and on the QOL of their
      patients.

PMID- 20152580
TI  - Health related quality of life in NCI-sponsored cancer treatment trials.
AB  - OBJECTIVE: To highlight health related quality of life (HRQOL) measures and
      published outcomes in phase III clinical trials in the four major cancers:
      breast, prostate, colorectal, and lung. DATA SOURCES: Peer-reviewed journals,
      textbooks, and abstracts published between 1990 and 2009. CONCLUSION: Over the
      past 20 years there has been an upsurge in the number and types of HRQOL measures
      used in phase III cancer treatment trials. Results of trials reported after 2001
      indicate a significant increase in specific treatment or disease-related symptom
      measures in lieu of or as companions to global HRQOL measures. Currently, open
      NCI-supported trials are incorporating a large number of targeted treatment-
      and/or disease-related measures. IMPLICATIONS FOR NURSING PRACTICE: Clinicians
      can use these data to help patients better understand the spectrum and severity
      of symptomatic toxicities they will experience with cancer treatment.

PMID- 20152581
TI  - Re: Update on cancer pain guidelines.

PMID- 20152582
TI  - Differences in performance of euthanasia and continuous deep sedation by French-
      and Dutch-speaking physicians in Brussels, Belgium.

PMID- 20152583
TI  - Targeting diuretic use for malignant ascites--two case reports highlighting the
      value of the serum-ascites albumin gradient in a palliative setting.

PMID- 20152584
TI  - A new combination cream for the treatment of severe neuropathic pain.

PMID- 20152585
TI  - Neuroleptic dose in the management of delirium in patients with advanced cancer.
AB  - Neuroleptics are commonly used in the management of delirium. Limited information
      is available regarding the dosage requirements and efficacy of neuroleptics in
      the palliative care setting. We determined the type and dose of neuroleptic use
      by delirium subtype. The medical records of 99 inpatients with advanced cancer
      were reviewed retrospectively. The doses of different neuroleptics, expressed as
      haloperidol equivalent daily doses (HEDDs), were correlated with delirium recall,
      recalled delirium symptom frequency, and associated distress from the patients',
      family caregivers', nurses' and palliative care specialists' perspectives.
      Subtypes of delirium included hypoactive in 20 (20%), mixed in 66 (67%), and
      hyperactive in 13 (13%). The median HEDD was 2.5mg, interquartile range (Q1-Q3) 1
      4.7 mg (mean 4.0+/-5.9 mg), and it was significantly higher in agitated and mixed
      delirium as compared with hypoactive delirium (P=0.008). The neuroleptic dose was
      low and appeared to be ineffective in preventing patient delirium recall, with 73
      (74%) patients remembering their episode of delirium as distressing. HEDD did not
      correlate with delirium recall, recalled symptom frequency, or distress for
      patients and family caregivers. However, HEDD increased with nurses' distress
      related to patients' symptoms (disorientation to place P=0.002, disorientation to
      time P=0.008, delusions P=0.041, and agitation P<0.001), and palliative care
      specialists' distress related to patients' hallucinatory symptoms (P=0.006) and
      agitation (P=0.006). In this study, the administered neuroleptic dose was
      influenced more by health care professional distress than by delirium symptom
      frequency. Future studies should examine the efficacy of neuroleptic dose
      according to individual delirium symptoms.

PMID- 20152586
TI  - Implementation of computer-based quality-of-life monitoring in brain tumor
      outpatients in routine clinical practice.
AB  - CONTEXT: Computerized assessment of quality of life (QOL) in patients with brain
      tumors can be an essential part of quality assurance with regard to evidence
      based medicine in neuro-oncology. OBJECTIVES: The aim of this project was the
      implementation of a computer-based QOL monitoring tool in a neurooncology
      outpatient unit. A further aim was to derive reference values for QOL scores from
      the collected data to improve interpretability. METHODS: Since August 2005,
      patients with brain tumors treated at the neuro-oncology outpatient unit of the
      Innsbruck Medical University were consecutively included in the study. QOL
      assessment (European Organisation for Research and Treatment of Cancer [EORTC]
      Quality of Life Questionnaire [QLQ-C30] plus the EORTC QLQ-brain cancer module
      [BN20]) was computer-based, using a software tool called the Computer-based
      Health Evaluation System. RESULTS: A total of 110 patients with primary brain
      tumors (49% female; mean [standard deviation] age 47.9 [12.6] years; main
      diagnoses: 30.9% astrocytoma, 17.3% oligodendroglioma, 17.3% glioblastoma, 13.6%
      meningioma) was included in the study. On average, QOL was assessed 4.74 times
      per patient, 521 times in total. The user-friendly software was successfully
      implemented and tested. The routine QOL assessment was found to be feasible and
      was well accepted by both physicians and patients. CONCLUSION: The software
      generated graphic QOL profiles were found to be an important tool for screening
      patients for clinically relevant problems. Thus, computer-based QOL monitoring
      can contribute to an optimization of treatment (e.g., symptom management,
      psychosocial interventions) and facilitate data collection for research purposes.

PMID- 20152587
TI  - Patterns of pain and interference in patients with painful bone metastases: a
      brief pain inventory validation study.
AB  - Bone metastases are prevalent, painful, and carry a poorer prognosis for pain
      control compared with other cancer pain syndromes. Standard tools to measure pain
      have not been validated in this patient population, and particular subgroups with
      more challenging symptoms have yet to be identified and studied. The objectives
      of this study were 1) to validate the psychometric properties of the Brief Pain
      Inventory (BPI) and its Pain and Interference subscales in patients with
      clinically significant metastatic bone pain requiring palliative radiotherapy and
      2) to examine differences in BPI subscales among predefined subgroups of bone
      metastases patients. A total of 258 patients evaluated and treated through a
      rapid access radiation therapy clinic between July 2002, and November 2006, were
      included in the analysis. High internal consistency of the BPI subscales of Pain,
      Activity interference, and Affect interference was demonstrated by Cronbach's
      alpha between 0.81 and 0.89. Removing sleep interference improved model fit in
      confirmatory factor analysis. The BPI revealed an alarming pattern in patients
      with lower body metastases, who reported substantial interference of activity
      even though pain levels were mild or moderate. Such patients may require prompt
      clinical attention to better meet their needs. Finally, the allocation of
      interference from sleep within the BPI framework, in our population of pain
      patients, requires further study.

PMID- 20152588
TI  - Evaluating correlation and interrater reliability for four performance scales in
      the palliative care setting.
AB  - Performance scales are used by clinicians to objectively represent a patient's
      level of function and have been shown to be important predictors of response to
      therapy and survival. Four different scales are commonly used in the palliative
      care setting, two of which were specifically developed to more accurately
      represent this population. It remains unclear which scale is best suited for this
      setting. The objectives of this study were to determine the correlations among
      the four scales and concurrently compare interrater reliability for each.
      Patients were each assessed at the same point in time by three different health
      care professionals, and all four scales were used to rate each patient. Spearman
      correlation coefficient values and both weighted and unweighted kappa values were
      calculated to determine correlation and interrater reliability. The results
      confirmed highly significant linear correlation among and between all four
      scales. Whether using a reliability measure that incorporates the concept of
      "partial credit" for "near misses" or a measure reflecting exact rater agreement,
      no one scale emerged as having a significantly higher likelihood of agreement
      among raters. We propose that what may be more important than clinical experience
      or rater profession is the level of training an individual health care
      professional rater receives on the administration of any particular performance
      scale. In addition, given that low levels of exact rater agreement could have
      substantial clinical implications for patients, we suggest that this parameter be
      considered in the design of future comparative studies.

PMID- 20152589
TI  - Retrospective assessment of cancer pain management in an outpatient palliative
      radiotherapy clinic using the Pain Management Index.
AB  - CONTEXT: The Pain Management Index (PMI) is a simple index linking the usual
      severity of cancer pain with the category of medication prescribed to treat it.
      Medication categories are derived from the World Health Organization's "analgesic
      ladder" approach to cancer pain, and the PMI is an indicator of the extent to
      which the medication prescribed corresponds to the recommended categories for
      mild, moderate, and severe pain. OBJECTIVES: The aim of this study was to assess
      prevalence of inadequate pain management in an outpatient palliative radiotherapy
      clinic using the PMI. METHODS: All patients with bone metastases referred for
      palliative radiotherapy from 1999 to 2006 were retrospectively analyzed for
      patient-rated pain scores (0-10 scale) and analgesic consumption. Pain scores
      were assigned 0, 1, 2, and 3 when patients reported no pain (0), mild (1-4),
      moderate (5-6), or severe pain (7-10), respectively. Analgesic scores of 0, 1, 2,
      and 3 were assigned when patients were prescribed no pain medication, nonopioids,
      "weak" opioids, and "strong" opioids, respectively. The PMI score was calculated
      by subtracting the pain score from the analgesic score. A negative PMI score was
      considered an indicator of potentially inadequate pain management by the
      prescriber. Descriptive statistics, Pearson's r correlation, and univariate and
      multivariate logistic regression analysis were used to determine the relationship
      of PMI over time, and the relationship with predictive factors. RESULTS: One
      thousand patients were included from January 1999 to December 2006. A negative
      PMI was calculated for 25.8% of patients at initial consultation. Prevalence of
      negative PMI significantly increased over years (P<0.0001). Higher Karnofsky
      Performance Status (P<0.0001) and breast primary cancer site (P<0.0001) were
      significantly associated with negative PMI after adjusting for year variable.
      CONCLUSION: Despite publication of numerous cancer pain management guidelines,
      undermedication appears to be a persistent problem for patients with painful bone
      metastases referred for radiotherapy.

PMID- 20152590
TI  - The association between autonomic dysfunction and survival in male patients with
      advanced cancer: a preliminary report.
AB  - CONTEXT: Autonomic nervous system dysfunction (AD) is a common syndrome in
      patients with advanced cancer. It is associated with decreased survival in
      several patient populations, including diabetes mellitus, heart failure, and
      neurological diseases. Based on this evidence, we hypothesized that autonomic
      dysfunction is associated with decreased survival in patients with advanced
      cancer. OBJECTIVES: The objective of this preliminary study was to test the
      association between AD, as measured by the standardized Ewing test and heart rate
      variability (HRV) measures, and survival in this patient population. METHODS: We
      examined the relationship between survival and parameters of AD in subjects who
      participated in a prospective study of autonomic dysfunction and hypogonadism in
      male patients with advanced cancer. Eligibility criteria were defined based on
      the prospective study protocol. We collected demographic information, date of
      death (obtained from the online Social Security Death Index database), date of
      study entry, and Ewing and HRV scores. We defined survival as the interval
      between study entry and date of death. A survival analysis was used to test the
      association between survival (in days) and Ewing test (0-5) and measures of HRV,
      including time domain (standard deviation of normal to normal beat interval
      [SDNN]) and frequency domain (ultra low, very low, low, and high). Four patients
      were still alive at the time of this study and included in the survival analysis
      as being censored. RESULTS: Forty-seven male patients were included in this
      study. Median age was 59 years (range: 20-79), and 30 out of 47 (63%) were
      Caucasians. AD, defined as Ewing score greater than 2, was present in 38 out of
      47 (80%) of the patients. Median Ewing score was 3 (1-5), indicating moderate to
      severe AD. Spearman correlation for Ewing score and SDNN was 0.44 (P = 0.002).
      There was a significant association between abnormal Ewing score and survival (P
      < 0.0001) and abnormal SDNN HRV and survival (P = 0.056). CONCLUSION: AD is
      associated with shorter survival in male patients with advanced cancer. Further
      longitudinal research in a large cohort is justified based on.

PMID- 20152591
TI  - Palliating a pandemic: "all patients must be cared for".
AB  - In the event of an overwhelming influenza pandemic, many health care systems will
      implement a triage system that would potentially deny critical care treatment to
      some seriously ill patients. Although all triage systems have guaranteed
      palliative care for those who are denied critical care, no jurisdiction has yet
      developed a plan to accommodate the anticipated "surge" in demand for palliative
      care. The authors present a mathematical and ethical justification for a
      palliative care surge plan and outline some of the key elements that should be
      included in such a plan.

PMID- 20152592
TI  - A systematic review of oxymorphone in the management of chronic pain.
AB  - Opioids are recommended for control of moderate-to-severe, chronic, malignant,
      and nonmalignant pain. A controlled-release formulation of the opioid oxymorphone
      has recently been launched. The aim of this review was to assess the
      effectiveness of oxymorphone as an analgesic in chronic pain. A systematic search
      for published studies of oral oxymorphone in the management of chronic pain was
      conducted. The studies were evaluated for their internal validity according to
      standard criteria. They were also evaluated for their external validity and
      research ethic aspects. A meta-analysis was performed to examine the effect of
      oxymorphone compared with placebo. Nine studies were evaluated; three were
      excluded because of low quality. Six controlled studies (duration 2-12 weeks)
      included a total of 1489 subjects suffering from chronic low back pain, chronic
      pain from osteoarthritis, and chronic cancer pain. Three of the studies were of
      high quality and three of medium quality. External validity was assessed to be
      high, medium, and low (in one, three, and two studies, respectively). The meta
      analysis suggests that daily doses of 40-100mg are superior to placebo; however,
      the estimate (reduction of pain intensity compared with placebo) of the treatment
      effect is imprecise (95% confidence interval -17.08, -8.69). Limited evidence
      suggests that oxymorphone is effective for pain control in patients with cancer.
      No significant differences between oxymorphone and oxycodone at equipotent doses
      were found. In conclusion, oxymorphone is superior to placebo. There is no
      evidence that the efficacy of oxymorphone differs from other opioids.

PMID- 20152593
TI  - Opioids, iatrogenic harm and disclosure of medical error.
AB  - The safety of patients in U.S. hospitals is a serious problem, with adverse
      events because of medical error affecting a significant proportion of
      hospitalized patients. Patients at the end of life are particularly vulnerable
      and are at risk of potential adverse events. This article presents a case in
      which opioids were rapidly titrated to neurotoxic doses in a patient who was
      terminally extubated. The patient was profoundly sedated and was noted to have
      Cheyne-Stokes breathing. The possibility of opioid-related iatrogenic harm is
      raised, and a discussion of what counts as medical error in these circumstances
      is explored. Palliative care specialists have a unique responsibility to provide
      guidance and establish a standard of care that clinicians should adhere to.
      Prevention of harm in dying patients should be a priority in the hospital
      setting.

PMID- 20152594
TI  - Endophthalmitis.

PMID- 20152595
TI  - Double-bubble technique to facilitate Descemet membrane exposure in deep anterior
      lamellar keratoplasty.
AB  - Safe and efficient exposure of Descemet membrane is the key to success in deep
      anterior lamellar keratoplasty. Although widely used, the big-bubble technique
      has the drawback of difficulty in maintaining appropriate needle insertion depth
      in the corneal stroma, resulting in injected air sometimes escaping to the
      peripheral cornea without separation of Descemet membrane. We describe a
      variation of the big-bubble technique in which air is injected into the anterior
      chamber before it is injected into the stroma. By observing the reflection
      created on the surface of the air, a needle can be inserted deep into the stroma
      without puncturing Descemet membrane. This allows safe and efficient separation
      of Descemet membrane. Moreover, air in the anterior chamber can be used as an
      indicator of successful Descemet membrane separation as air is shifted to the
      periphery with creation of the big bubble.

PMID- 20152596
TI  - Crossed-swords, capsule-pinch technique for capsulotomy in pediatric and/or loose
      lens cataract extraction.
AB  - Puncturing the anterior capsule in a patient with a very soft lens, an elastic
      capsule, and/or deficient zonular countertraction can be challenging even with a
      sharp needle or blade. The crossed-swords, capsule-pinch technique capitalizes on
      opposing forces from 2 needles directed toward each other with a "pinch" of the
      capsule between their tips. This affords a controlled and facile puncture of the
      capsule without creating stress on the zonules or anteroposterior displacement of
      the lens.

PMID- 20152597
TI  - Repositioning free laser in situ keratomileusis flaps.
AB  - We describe a protocol for adequate repositioning of free laser in situ
      keratomileusis (LASIK) corneal flaps created by a Moria M2 microkeratome even in
      the absence of fiduciary marks. In an enucleated porcine globe, a free flap was
      created by initially placing a longitudinal incision at the proposed hinge site
      followed by activating the forward pass of the automated microkeratome. A
      protocol was devised based on placement of a positioning dot on the free flap
      before the flap is retrieved from the microkeratome head. Preplaced surgical
      landmarks were used as a guide to determine the correct alignment of the free
      flap. Adequate orientation of the free flap to the stromal bed was achieved in 9
      porcine eyes using the positioning dot method. The technique is applicable to the
      Moria M2 microkeratome only and must be validated for other types of keratomes.

PMID- 20152598
TI  - Effectiveness of intracameral cefuroxime in preventing endophthalmitis after
      cataract surgery Ten-year comparative study.
AB  - PURPOSE: To determine the differences in the endophthalmitis rates in cataract
      surgery before and after prophylactic use of intracameral cefuroxime. SETTING:
      University Hospital Fundacion Alcorcon, Madrid, Spain. METHODS: This prospective
      study evaluated patients who had cataract surgery at a university eye center over
      a 10-year period (1999 to 2008). Since the protocol's approval by the Hospital
      Board in October 2005 to the end of the 10-year period, cataract patients were
      routinely treated with prophylactic intracameral cefuroxime. A database was used
      to measure the occurrence of endophthalmitis postoperatively. Then, the incidence
      of endophthalmitis before and after generalized use of prophylactic cefuroxime
      was compared. The effect of cefuroxime was evaluated by the relative risk.
      RESULTS: From January 1999 to December 2008, 13 652 patients had cataract
      surgery. Forty-two cases of postoperative bacterial endophthalmitis were
      reported. The endophthalmitis rate was 0.30% (95% confidence interval [CI], 0.26%
      0.35%) overall, 0.59% (95% CI, 0.50%-0.70%) from January 1999 to September 2005,
      and 0.043% (95% CI, 0.02%-0.06%) from October 2005 to December 2008. The relative
      risk was 0.07 (range 0.022 to 0.231; P<.05). CONCLUSION: Intracameral cefuroxime
      proved to be effective in reducing the risk for acute-onset endophthalmitis after
      cataract surgery.

PMID- 20152599
TI  - Role of anterior capsule polishing in residual lens epithelial cell
      proliferation.
AB  - PURPOSE: To determine the role of anterior capsule polishing in residual lens
      epithelial cell (LEC) proliferation. SETTING: Zhongshan Ophthalmic Center, Sun
      Yat-sen University, Guangzhou, China. METHODS: Phacoemulsification was performed
      on pairs of human cadaver eyes. One eye of each pair had anterior capsule
      polishing; the fellow eye did not. Capsular bags with implanted intraocular
      lenses (IOLs) were incubated in culture. Specimens were observed and photographed
      under microscopy. For clinical comparison, both eyes of patients who had
      phacoemulsification and IOL implantation with anterior capsule polishing in 1 eye
      only were observed for 1 year postoperatively. RESULTS: The study comprised 10
      pairs of cadaver eyes and 20 eyes of 10 patients. One day after surgery, large
      patches of cells remained under the anterior capsule and the equatorial zone in
      the unpolished cadaver eyes and the anterior capsule was clear in the polished
      eyes. By 3 days in culture, many patches of dead cells had formed in the
      unpolished eyes. After 7 days in culture, cell growth was minimal in the
      unpolished eyes; however, robust cell proliferation was observed in the polished
      eyes. In the clinical comparison, there was no obvious difference in the mean
      subjectively assessed fibrotic posterior capsule opacification (PCO) score
      between polished eyes and unpolished eyes at 1 year. CONCLUSIONS: Anterior
      capsule polishing, although it removed many LECs, did not decrease residual cell
      growth and, conversely, enhanced cell proliferation in capsular bag cultures.
      This might explain why polishing does not reduce PCO in clinical studies.

PMID- 20152600
TI  - Effect of intraocular lens asphericity on vertical coma aberration.
AB  - PURPOSE: To analyze the effect of asphericity of intraocular lenses (IOLs) on
      vertical coma aberration after implantation of spherical, spherically neutral,
      and aspheric IOLs. SETTING: Department of Ophthalmology, St. Thomas' Hospital,
      London, United Kingdom. METHOD: This observational study recruited patients from
      previous prospective randomized fellow-eye controlled studies comparing aspheric
      and spherical IOLs (3 spherical, 1 spherically neutral, and 2 aspheric IOLs). At
      postoperative follow-up visits, maximum pupil dilation was achieved and
      aberrometry was performed using an iTrace aberrometer with a pupil scan size of
      5.0 mm. Data on Zernike coefficients Z(3,-1) (vertical coma), Z(3,+1) (horizontal
      coma), and Z(4,0) (spherical aberration) and on IOL power were extracted.
      RESULTS: Two hundred eyes of 100 patients were recruited. Ninety-two eyes had a
      spherical IOL, 32 eyes had a spherically neutral IOL, and 76 eyes had an aspheric
      IOL. Vertical coma Z(3,-1) and spherical aberration Z(4,0) values were highest
      with the spherical IOLs and lowest with the aspheric IOLs (P = .0163 and P<.0001,
      respectively). There was no difference in horizontal coma aberration between the
      3 IOL groups. There was no correlation between IOL power and vertical coma
      aberration (r(2) = 0.0135, P = .1169). CONCLUSIONS: Conventional spherical IOLs
      induced more vertical coma than newer aspheric and spherically neutral IOLs.
      Vertical coma aberration enhances the depth of focus; thus, newer aspheric and
      spherically neutral designs of IOLs may negatively affect uncorrected near
      vision.

PMID- 20152601
TI  - Assessment of toric intraocular lens alignment by a refractive power/corneal
      analyzer system and slitlamp observation.
AB  - PURPOSE: To assess the validity of an internal optical path difference map of a
      refractive power/corneal analyzer system in determining the alignment of toric
      intraocular lenses (IOLs). SETTINGS: Private practices, Spring Hill, Brisbane,
      and Chermside, Australia. METHODS: This retrospective study comprised patients
      with more than 1.5 diopters of preexisting corneal astigmatism who had
      phacoemulsification and AcrySof toric IOL implantation. Preoperatively, the
      surgical eye was marked at the slitlamp microscope using a 4-point technique. The
      desired IOL orientation was marked with a Mendez marker based on the steep
      corneal axis. The toric IOL axis was measured 3 weeks postoperatively by rotating
      the slitlamp beam to align with the IOL axis indicator marks and using the
      Internal OPD Map on the Nidek OPD-Scan system. Uncorrected (UDVA) and corrected
      (CDVA) distance visual acuities, residual refractive sphere, and residual
      keratometric and refractive cylinders were also measured at 3 weeks. RESULTS:
      Postoperatively, the mean UDVA was 0.17 logMAR +/- 0.18 (SD) and the mean CDVA, 
      0.01 +/- 0.12 logMAR; 88.2% of eyes had a UDVA of 0.3 or better, and no eye lost
      lines of visual acuity. There was an 82.33% reduction in defocus equivalent and a
      64.62% reduction in refractive cylinder. The mean IOL misalignment measured by
      slitlamp was 2.55 +/- 2.76 degrees and by the internal map, 2.65 +/- 1.98
      degrees. The correlation between the 2 methods was highly significant (r = 0.99,
      P<.001). CONCLUSIONS: Both refractive power/corneal analyzer system and slitlamp
      observation were reliable and predictable methods of assessing IOL alignment. The
      4-point preoperative marking technique yielded clinically acceptable, accurate
      toric IOL alignment.

PMID- 20152602
TI  - Intraocular lens power calculation: clinical comparison of 2 optical biometry
      devices.
AB  - PURPOSE: To evaluate intraocular lens (IOL) power calculation using a new optical
      low-coherence reflectometry (OLCR) biometer and compare the results with those
      obtained with a partial coherence interferometry (PCI) optical biometer. SETTING:
      International Vision Correction Research Centre, Department of Ophthalmology,
      University of Heidelberg, Heidelberg, Germany. METHODS: Biometry measurements in
      eyes of cataract patients were performed by the same examiner with an OLCR
      biometer (Lenstar LS 900/Allegro Biograph) and a PCI optical biometer
      (IOLMaster). After determination of axial length (AL), corneal radii values by
      keratometry (R1 and R2), and anterior chamber depth (ACD), power calculation for
      an AcrySof MA60AC IOL was compared between the 2 devices using 4 formulas and the
      corresponding IOL constants. The target was emmetropia. RESULTS: One hundred eyes
      of 100 cataract patients (mean age 70.0 years +/- 10.6 [SD]) were measured. Of
      the biometry parameters, the only statistically significant differences between
      the 2 devices were in R2 (mean difference 0.02 +/- 0.05 mm), (R1 + R2)/2 (mean
      difference 0.01 +/- 0.04 mm), and ACD (mean difference 0.05 +/- 0.11 mm) (P<.01,
      Wilcoxon test). The mean differences in IOL power calculations using the 4
      formulas were not statistically significant between the 2 devices (P>.01,
      Wilcoxon test). CONCLUSION: The OLCR biometry device provided precise and valid
      measurements and thus can be used for the preoperative examination of cataract
      patients.

PMID- 20152603
TI  - Magnetic resonance imaging of the anteroposterior position and thickness of the
      aging, accommodating, phakic, and pseudophakic ciliary muscle.
AB  - PURPOSE: To quantify accommodative and age-related changes in the anteroposterior
      position and thickness of the ciliary muscle in phakic and pseudophakic eyes.
      SETTING: Department of Surgery/Bioengineering, UMDNJ-Robert Wood Johnson Medical
      School, Piscataway; Institute of Ophthalmology and Visual Science UMDNJ-New
      Jersey Medical School, Newark, New Jersey; MRI Research, Inc., Middleburg
      Heights, Ohio, USA. METHODS: Magnetic resonance images were taken of phakic and
      pseudophakic eyes. RESULTS: The cohort comprised 32 phakic volunteers and 8
      volunteers with a monocular intraocular lens (IOL) aged 22 to 91 years. No
      anteroposterior accommodative movement of the ciliary muscle apex occurred in
      either group. The muscle moved closer to the cornea with advancing age in phakic
      eyes; IOL implantation returned the muscle to a youthful position. An age
      dependent increase in ciliary muscle anteroposterior thickness occurred that was
      not mitigated by IOL implantation. Muscle thickness increased with accommodation
      in only phakic eyes. CONCLUSIONS: Presbyopia-correction strategies cannot rely on
      accommodative anterior movement of the ciliary muscle. Forces on the uvea by
      crystalline lens-pupillary margin contact may increase with accommodation and
      lens growth, producing accommodative and age-dependent increases in muscle
      thickness and significant age-dependent anterior muscle displacement. Intraocular
      lens implantation removed these forces, allowing choroidal elasticity to restore
      the muscle to a youthful position; however, the increase in thickness was
      permanent and likely due to an age-dependent increase in connective tissue. This
      supports the geometric theory of presbyopia development and that the mechanical
      forces in human accommodation and presbyopia are very different from those in the
      rhesus monkey model.

PMID- 20152604
TI  - Preoperative cataract grading by Scheimpflug imaging and effect on operative
      fluidics and phacoemulsification energy.
AB  - PURPOSE: To evaluate the power use, chamber stability, and surgical efficiency of
      a phacoemulsification system when cataracts were graded preoperatively using the
      Pentacam Nucleus Grading System (PNS) and adjustments were made in phaco
      parameters based on the cataract grade. SETTING: Royal Victoria Hospital, Barrie,
      Ontario, Canada. METHODS: Cataracts were graded using Scheimpflug imaging
      (Pentacam) in consecutive patients. In Group 1, surgery was performed with no
      change in parameters. In Group 2, adjustments were made preoperatively in
      fluidics and phaco power to reflect the cataract grade determined by Scheimpflug
      imaging. Parameters assessed in both groups included effective phaco time (EPT),
      balanced salt solution (BSS) use, and needle time to remove the cataract.
      RESULTS: There were 200 patients in each group. Emulsification and aspiration of
      higher and lower grades of cataract took statistically significantly less EPT and
      BSS in Group 2 (preoperative parameter adjustments) than in Group 1. The needle
      time for the higher grades of cataract was statistically significantly less in
      Group 2. For cataracts of a middle grade (2 to 3; 63% of cases), there was no
      statistically significant difference between standard phaco settings and adjusted
      settings. The cataract was effectively aspirated in both groups. CONCLUSION:
      Preoperatively adjusting phaco parameters based on cataract grade helped improve
      overall efficiency by reducing the amount of energy and fluid used in the eye and
      reducing overall phaco time.

PMID- 20152605
TI  - Comparison of endothelial cell loss after cataract surgery: phacoemulsification
      versus manual small-incision cataract surgery: six-week results of a randomized
      control trial.
AB  - PURPOSE: To compare endothelial cell loss in cataract surgery by
      phacoemulsification and by manual small-incision cataract surgery (SICS).
      SETTINGS: Tertiary care ophthalmic center, India. METHODS: A complete
      ophthalmologic examination and endothelial specular microscopy were performed
      preoperatively and 1 and 6 weeks postoperatively in patients having cataract
      surgery. The endothelial cell count (ECC) was calculated manually and
      automatically using an LSM 12000 specular microscope. Patients were randomly
      allocated to have SICS or phacoemulsification using a random number table.
      Phacoemulsification was performed using the stop-and-chop technique and SICS, by
      viscoexpression. RESULTS: The study evaluated 200 patients, 100 in each group.
      The mean preoperative ECC by the manual counting method was 2950.7 cells/mm(2) in
      the phacoemulsification group and 2852.5 cells/mm(2) in the SICS group and by the
      automated counting method, 3053.7 cells/mm(2) and 2975.3 cells/mm(2),
      respectively. The difference at 6 weeks was 543.4 cells/mm(2) and 505.9
      cells/mm(2), respectively, by the manual method (P = .44) and 474.2 cells/mm(2)
      and 456.1 cells/mm(2), respectively, by the automated method (P = .98). The
      corrected distance visual acuity at 6 weeks was better than 6/18 in 98.5% of eyes
      in the phacoemulsification group and 97.3% of eyes in the SICS group. CONCLUSION:
      There were no clinically or statistically significant differences in ECC loss or
      visual acuity between phacoemulsification and SICS, although there was a small
      difference in the astigmatic shift.

PMID- 20152606
TI  - Intermediate results of sutureless intrascleral posterior chamber intraocular
      lens fixation.
AB  - PURPOSE: To report the intermediate multicenter results of a technique of
      sutureless intrascleral fixation of a standard 3-piece posterior chamber
      intraocular lens (PC IOL) in the ciliary sulcus. SETTING: Four European
      ophthalmology centers. METHODS: A technique for sutureless intrascleral fixation
      of the haptics of a standard 3-piece PC IOL was retrospectively evaluated. The
      technique uses standardized maneuvers to fixate the PC IOL without need for
      special haptic architecture or preparation or haptic suturing. All patients
      having IOL implantation by the technique were evaluated for preoperative status
      (visual acuity, refractive error, preexisting ocular conditions, optical
      biometry), postoperative status, complications, and need for further surgery.
      RESULTS: The study evaluated 63 consecutive patients from 4 institutions (4
      surgeons). The median follow-up was 7 months. Two dislocated PC IOLs (3.6%) were
      decentered; the other 61 IOLs (96.8%) were stable and well centered. There were
      no cases of recurrent dislocation, endophthalmitis, retinal detachment, or
      glaucoma. CONCLUSION: Fixation of PC IOL haptics in a limbus-parallel scleral
      tunnel provided exact centration and axial stability of the IOL and prevented
      distortion and subluxation in most cases.

PMID- 20152607
TI  - Laser-assisted subepithelial keratectomy for bilateral hyperopia and hyperopic
      anisometropic amblyopia in children: one-year outcomes.
AB  - PURPOSE: To assess the refractive, visual acuity, and binocular results of laser
      assisted subepithelial keratectomy (LASEK) in children with bilateral hyperopia
      or hyperopic anisometropic amblyopia. SETTING: Nonhospital surgical facility and
      hospital clinic, Calgary, Alberta, Canada. METHODS: This retrospective review
      comprised children with bilateral hyperopia or hyperopic anisometropic amblyopia
      who had LASEK. Refractive status, visual acuity, and binocular vision were
      assessed and recorded 2 months and 1 year postoperatively. RESULTS: The mean
      spherical equivalent (SE) in all 72 hyperopic eyes (47 patients) was +3.42
      diopters (D) (range 0.00 to +12.50 D) preoperatively and +0.59 D (range -1.25 to
      +2.00 D) 1 year postoperatively. After LASIK, 41.7% of eyes had improved
      corrected distance visual acuity (CDVA). No patient had reduced CDVA or loss of
      fusional ability; there was a 25.0% improvement in stereopsis at 1 year. The mean
      anisometropic difference in the hyperopic anisometropic amblyopia subgroup (18
      eyes, 10 patients) was 4.39 D (range +1.75 to +7.75 D) preoperatively and +0.51 D
      (range 0 to +0.875 D) at 1 year. One year postoperatively, 83% of anisometropic
      eyes were within +/-1.00 D of the fellow eye and 94.0% were within +/-3.00 D.
      Postoperatively, 64.7% of eyes had improved CDVA with no reduced CDVA or loss of
      fusional ability; there was a 22% improvement in stereopsis at 1 year.
      CONCLUSION: Laser-assisted subepithelial keratectomy improved visual acuity in
      pediatric hyperopia with or without associated hyperopic anisometropic amblyopia.

PMID- 20152608
TI  - Ocular blood-flow hemodynamics before and after application of a laser in situ
      keratomileusis ring.
AB  - PURPOSE: To evaluate blood-flow responses before and after microkeratome
      application. SETTING: School of Life and Health Sciences, Aston University,
      Birmingham, United Kingdom. METHODS: Hemodynamic responses were measured in eyes
      of healthy volunteers before and after transient elevation in intraocular
      pressure (IOP) resulting from microkeratome application. The IOP was elevated
      above 85 mm Hg for 90 seconds. Blood-flow responses were measured using color
      Doppler imaging, Heidelberg retinal flowmetry, and an ocular blood-flow analyzer.
      RESULTS: The study included 10 eyes. There was no difference in ocular-perfusion
      measurements before or after IOP elevation using any measurement system.
      CONCLUSION: In normal healthy eyes, once suction was released, blood-flow
      responses returned immediately to normal levels.

PMID- 20152609
TI  - Collagen crosslinking with riboflavin and ultraviolet-A in eyes with pseudophakic
      bullous keratopathy.
AB  - PURPOSE: To evaluate the safety and efficacy of corneal collagen crosslinking
      (CXL) in patients with painful pseudophakic bullous keratopathy (PBK). SETTING:
      University of Sao Paulo, Sao Paulo and Sadalla Amin Ghanem Eye Hospital,
      Joinville, Santa Catarina, Brazil. METHODS: This prospective study included
      consecutive eyes with PBK that had CXL. After a 9.0 mm epithelial removal,
      riboflavin 0.1% with dextran 20% was applied for 30 minutes followed by
      ultraviolet-A irradiation (370 nm, 3 mW/cm(2)). Therapeutic contact lenses were
      placed for 1 week. Corneal transparency, central corneal thickness (CCT), and
      ocular pain were assessed preoperatively and 1 and 6 months postoperatively.
      Statistical analysis was by paired t tests. RESULTS: Fourteen patients (14 eyes)
      with a mean age 71.14 years +/- 11.70 (SD) (range 53 to 89 years) were enrolled.
      Corneal transparency was better in all eyes 1 month after surgery. At 6 months,
      corneal transparency was similar to preoperative levels (P = .218). The mean CCT
      was 747 mum preoperatively and 623 mum at 1 month; the decrease was statistically
      significant (P<.001). At 6 months, the mean CCT increased to 710 mum, still
      significantly thinner than preoperatively (P = .006). Pain scores at 6 months
      were not significantly different than preoperatively (P = .066). CONCLUSIONS:
      Corneal CXL significantly improved corneal transparency, corneal thickness, and
      ocular pain 1 month postoperatively. However, it did not seem to have a long
      lasting effect in decreasing pain and maintaining corneal transparency in
      patients with PBK.

PMID- 20152610
TI  - Clinical performance of a handheld digital infrared monocular pupillometer for
      measurement of the dark-adapted pupil diameter.
AB  - PURPOSE: To compare the accuracy of a handheld infrared digital pupillometer and
      digital infrared photography for measurement of the dark-adapted pupil diameter.
      SETTING: Department of Ophthalmology and Visual Sciences, Texas Tech University
      Health Sciences Center, Lubbock, Texas, USA. METHODS: The right horizontal pupil
      diameter in healthy volunteers was measured using a NeurOptics PLR-200
      pupillometer and then videographed using the infrared function of a CyberShot
      video camera after 2 minutes and 5 minutes dark adaptation at 1 lux ambient
      illumination. The best still image was extracted from the video file, and the
      horizontal pupil diameter was determined by comparison against an internal
      photographic length standard using digital image software. Accommodation and
      alertness were controlled during testing. RESULTS: The mean horizontal pupil
      diameter by infrared photography after 2 minutes of dark adaptation by subject
      age was 7.71 mm for ages 20 to 29 years, 6.80 mm for ages 30 to 39 years, 6.53 mm
      for ages 40 to 49 years, 5.94 mm for ages 50 to 59 years, and 6.01 mm for ages 60
      to 69 years. The mean difference (infrared photography minus pupillometer) was
      +0.09 mm (range +0.30 to -0.14 mm) at 2 minutes of adaptation and +0.07 mm (range
      +0.25 to -0.13 mm) at 5 minutes. CONCLUSIONS: The pupillometer accurately
      measured the horizontal pupil diameter at 1 lux, with no measurement more than
      0.3 mm different from infrared photography measurements. The pupillometer had a
      slight negative bias that is unlikely to introduce an error greater than 0.5 mm
      in clinical measurements.

PMID- 20152611
TI  - Visual function after monocular implantation of apodized diffractive multifocal
      or single-piece monofocal intraocular lens Randomized prospective comparison.
AB  - PURPOSE: To compare visual function after phacoemulsification with implantation
      of a multifocal intraocular lens (IOL) or a monofocal IOL. SETTING: Department of
      Ophthalmology, Affiliated Hospital of Qingdao University Medical College,
      Qingdao, Shandong, China. METHODS: This study comprised patients with unilateral
      cataract who had phacoemulsification with implantation of an AcrySof ReSTOR
      SA60D3 multifocal IOL (multifocal group) or an AcrySof SA60AT single-piece
      monofocal IOL (monofocal group). Postoperative visual function, including
      uncorrected (UDVA) and corrected (CDVA) distance visual acuity; uncorrected
      (UNVA), corrected (CNVA), and distance-corrected near visual acuity; and contrast
      sensitivity were evaluated 1 week, 1 month, and 6 months postoperatively. Patient
      reported vision and spectacle independence in the 2 groups were also compared.
      RESULTS: Of the 161 eyes, 72 were in the multifocal group and 89 were in the
      monofocal group. The multifocal group had statistically significant better UNVA
      than the monofocal group from 1 week postoperatively to the final follow-up and
      statistically significant better CNVA at 6 months (both P<.05). There were no
      statistically significant differences in UDVA or CDVA between the 2 groups over
      the 6-month follow-up. The multifocal group had statistically significantly
      better pseudoaccommodation than the monofocal group; the monofocal group had
      significantly better contrast sensitivity (both P<.05). Patients with the
      multifocal IOL reported being more satisfied than those with the monofocal IOL.
      CONCLUSIONS: The multifocal IOL provided better near visual acuity and more
      spectacle independence than the monofocal IOL.

PMID- 20152612
TI  - Assessing the accuracy of intracameral antibiotic preparation for use in cataract
      surgery.
AB  - PURPOSE: To evaluate 2 local dilution protocols to assess the accuracy and
      variability of intracameral antibiotic dosage in cataract surgery. SETTING:
      Tennent Institute of Ophthalmology, Glasgow, United Kingdom. METHODS: Ten
      ophthalmic operating room nurses from 2 local hospitals participated. Oven-dried
      analytical grade potassium chloride (KCl) was used as a surrogate for cefuroxime.
      Solutions intended for intracameral use (1.0 mg in 0.1 mL) were prepared
      according to the 2 protocols. Twenty samples were obtained for each protocol. Ten
      analytical chemists also performed both dilutions. Concentrations of KCl in each
      0.1 mL sample were analyzed by flame photometry. RESULTS: Thirty samples were
      obtained for each protocol. The median dose after dilution was 1.17 mg (range
      0.62 to 1.77 mg) for protocol 1 and 2.05 mg (range 0.52 to 7.25 mg) for protocol
      2. The median was significantly higher for protocol 2 (P < .001). There was also
      greater variability with protocol 2. CONCLUSIONS: This study shows that the
      mathematical accuracy of a dilution protocol does not ensure dosage accuracy in
      the clinical scenario. Inadequate mixing in a 1.0 mL syringe was probably
      responsible for the inaccuracy of protocol 2, indicating that small-volume
      syringes should not be used for mixing. However, protocol 1 had an acceptable
      range of variability. Replication of this study could evaluate other protocols
      and address concerns regarding the accuracy of intracameral antibiotic
      preparations.

PMID- 20152613
TI  - Uveal and capsular biocompatibility of an intraocular lens with a hydrophilic
      anterior surface and a hydrophobic posterior surface.
AB  - PURPOSE: To evaluate the uveal and capsular biocompatibility of intraocular
      lenses (IOLs) with a hydrophilic anterior surface and a hydrophobic posterior
      surface in a rabbit model. SETTING: Eye Center, Affiliated Second Hospital,
      College of Medicine, Zhejiang University, Hangzhou, China. METHODS: Modified
      silicone IOLs were produced by grafting 2-methacryloyloxyethyl phosphorylcholine
      (MPC) onto the anterior IOL surface using a plasma technique. A contact-angle
      test characterized the hydrophilicity of the IOL surface; physical and optical
      properties were determined by State Food and Drug Administration (SFDA)
      standards. Rabbits had phacomulsification and implantation a modified silicone
      IOL, a control silicone IOL, or a hydrogel IOL. Postoperative inflammation was
      assessed by aqueous flare measurement, and PCO was evaluated by software
      analysis. Three months after surgery, attached cells on extracted IOLs were
      evaluated by light microscopy; PCO was evaluated by Miyake-Apple technique.
      Histologic sections of globes were used to assess lens epithelial cells (LECs)
      and extracellular matrix in the capsular bag. RESULTS: Contact angle data showed
      the MPC-modified IOL had a hydrophilic anterior surface and hydrophobic posterior
      surface. The properties of the modified IOLs met SFDA standards. There was no
      statistical difference in aqueous flare between the IOL groups at any time. The
      modified and control IOLs had less PCO than the hydrogel IOLs (P<.05). There were
      fewer cells on modified IOLs than on silicone IOLs (P<.05). The LECs and cortical
      remnants on modified IOLs had a rapid, fibroblastic appearance at the optic
      periphery; the center was clear. CONCLUSIONS: Results suggest that the MPC
      modified IOL has excellent uveal and capsule biocompatibility from hydrophilic
      anterior surface and hydrophobic posterior surface properties, respectively.

PMID- 20152614
TI  - Transmission spectrums and retinal blue-light irradiance values of untinted and
      yellow-tinted intraocular lenses.
AB  - PURPOSE: To record and compare the spectral transmission characteristics of
      foldable untinted and yellow-tinted intraocular lenses (IOLs) and evaluate the
      protective effects against retinal damage by sunlight. SETTING: Shimane
      University Faculty of Medicine, Izumo, Japan. METHODS: The study evaluated 3
      untinted IOLs (SA60AT, VA-60BBR, AU6 K) and 3 yellow-tinted IOLs (SN60AT, YA
      60BBR, AU6 N) of 3 lens powers (+10.0 diopters [D], +20.0 D, and +30.0 D).
      Spectral transmittance in the wavelength range of 300 to 800 nm was measured
      using a spectrophotometer through 2.5 mm and 4.5 mm diameter apertures. Retinal
      hazard indices, including blue-light irradiance and maximum permissible exposure
      duration per day (t(max)) for viewing sunlight, were calculated. RESULTS: The
      untinted IOLs completely absorbed ultraviolet (UV) light and nearly completely
      absorbed transmitted visible light at wavelengths longer than 440 nm. Yellow
      tinted IOLs absorbed more in the blue-light range (400 to 500 nm) than untinted
      IOLs. The blue-light irradiance was 34.2% to 56.0% lower with the SN60AT IOL than
      with the SA60AT IOL, 35.2% to 48.4% lower with the YA-60BBR IOL than with the VA
      60BBR IOL, and 16.8% to 22.9% lower with the AU6 N IOL than with the AU6 K IOL.
      Blue-light irradiance values of SN60AT and YA-60BBR IOLs decreased as the lens
      power increased. CONCLUSIONS: Compared with aphakic eyes, UV-blocking untinted
      IOLs reduced the blue-light irradiance value by 60%; yellow-tinted IOLs conferred
      an additional 17% to 56% reduction. The difference in lens power was
      significantly related to the blue-light irradiance value of some yellow-tinted
      IOLs. .

PMID- 20152615
TI  - Age-related changes in the transmission properties of the human lens and their
      relevance to circadian entrainment.
AB  - PURPOSE: To characterize age-related changes in the transmission of light through
      noncataractous human lenses. SETTING: Department of Ophthalmology, Glostrup
      Hospital, Glostrup, Denmark. METHODS: The spectral transmission of white light
      was measured along the visual axis in the most central part of the lens in vitro
      in intact human donor lenses over a wide range of ages. RESULTS: The study
      evaluated 28 intact human donor lenses of 15 donors aged 18 to 76 years.
      Increasing age was associated with gradually decreasing transmission at all
      visible wavelengths, most prominently at shorter wavelengths. Empirical formulas
      describing the age-related loss of transmission were created for each spectral
      color. At 480 nm, the absorption peak for melanopsin, transmission decreased by
      72% from the age of 10 years to the age of 80 years. CONCLUSION: The age-related
      decrease in spectral transmission through the human lens could be modeled by a
      simple algorithm that may be useful in the design of intraocular lenses that
      mimic the characteristics of the human lens and in studies of color vision,
      psychophysics, and melanopsin activation.

PMID- 20152616
TI  - Wave aberration of human eyes and new descriptors of image optical quality and
      visual performance.
AB  - The expansion of wavefront-sensing techniques redefined the meaning of refractive
      error in clinical ophthalmology. Clinical aberrometers provide detailed
      measurements of the eye's wavefront aberration. The distribution and contribution
      of each higher-order aberration to the overall wavefront aberration in the
      individual eye can now be accurately determined and predicted. Using corneal or
      ocular wavefront sensors, studies have measured the interindividual and age
      related changes in the wavefront aberration in the normal population with the
      goal of optimizing refractive surgery outcomes for the individual. New objective
      optical-quality metrics would lead to better use and interpretation of newly
      available information on aberrations in the eye. However, the first metrics
      introduced, based on sets of Zernike polynomials, is not completely suitable to
      depict visual quality because they do not directly relate to the quality of the
      retinal image. Thus, several approaches to describe the real, complex optical
      performance of human eyes have been implemented. These include objective metrics
      that quantify the quality of the optical wavefront in the plane of the pupil (ie,
      pupil-plane metrics) and others that quantify the quality of the retinal image
      (ie, image-plane metrics). These metrics are derived by wavefront aberration
      information from the individual eye. This paper reviews the more recent knowledge
      of the wavefront aberration in human eyes and discusses the image-quality and
      optical-quality metrics and predictors that are now routinely calculated by
      wavefront-sensor software to describe the optical and image quality in the
      individual eye.

PMID- 20152617
TI  - Enhanced effect of double-stacked intrastromal corneal ring segments in
      keratoconus.
AB  - We present a patient with poor visual acuity and contact lens intolerance due to
      advanced keratoconus who had femtosecond-assisted placement of two 0.35 mm
      intrastromal corneal ring segments (ICRS) in the right eye. Postoperatively, both
      rings migrated inferiorly and overlapped each other in a double-stacked
      formation. This resulted in a dramatic central shift of the cone and flattening
      of the inferior paracentral cornea with significant improvement in vision. To our
      knowledge, this is the first report of double-stacked ICRS in a human cornea and
      raises the possibility that significantly thicker segments may provide enhanced
      anatomic and visual effects in some keratoectatic patients.

PMID- 20152618
TI  - Intrastromal corneal ring segments for post-LASIK ectasia complicated by
      persistent pain.
AB  - A 33-year-old man who was 2 years post laser in situ keratomileusis was found to
      have corneal ectasia. He was intolerant of rigid gas-permeable contact lenses and
      eventually chose to have placement of intrastromal corneal ring segments (ICRS)
      (Intacs) in the right eye. Two ICRS were implanted without complication, and
      postoperative examination showed improved visual acuity and decreased corneal
      elevation on scanning-slit tomography imaging. However, over the following 2
      months, he complained of persistent pain in the right eye. Confocal microscopy
      showed a corneal nerve touching the superonasal ICRS. The ICRS was removed, and
      shortly thereafter the patient's pain resolved.

PMID- 20152619
TI  - Brevundimonas vesicularis keratitis after laser in situ keratomileusis.
AB  - A 45-year-old woman developed a corneal infiltrate 14 months after laser in situ
      keratomileusis (LASIK) enhancement in the left eye. The LASIK flap was lifted,
      scraped, and irrigated with fortified vancomycin and ceftazidime. Scraped samples
      were cultured and grew Brevundimonas vesicularis. The patient remained on topical
      ceftazidime until improvement was noted and was then switched to topical
      levofloxacin. The keratitis resolved on antibiotic agents with strong gram
      negative coverage and a steroid. To our knowledge, this is the first report of a
      B vesicularis ocular infection.

PMID- 20152620
TI  - Toxic anterior segment syndrome after cataract surgery.
AB  - We report a case of toxic anterior segment syndrome (TASS) that developed after
      cataract surgery. A 78-year-old woman had uneventful phacoemulsification via a
      clear corneal incision with implantation of an acrylic intraocular lens. One day
      postoperatively, diffuse corneal edema and anterior chamber inflammation were
      evident. Topical antibiotic and steroid eyedrops were prescribed. The anterior
      chamber reaction decreased considerably, but corneal edema persisted. After a
      thorough investigation, the antiseptic solution used to soak surgical instruments
      before subsequent surgery was identified as the source of the problem.

PMID- 20152621
TI  - Accommodating intraocular lens implantation in an epikeratophakia patient.
AB  - We report a case of implantation of the Crystalens AT-45SE and AT-52SE
      intraocular lenses in a highly myopic patient who had bilateral epikeratophakia
      surgery 15 years previously. Lessons learned from the first eye were taken into
      consideration when selecting the dioptric power for the fellow eye. With
      secondary interventions and meticulous lens calculations, the final outcomes were
      excellent and equivalent, allowing the patient to achieve uncorrected distance
      and intermediate visual acuities of 20/25 and near visual acuity of 20/50 in both
      eyes. To our knowledge, this is the first reported case of accommodating lens
      implantation in an epikeratophakic eye.

PMID- 20152622
TI  - Iris fingerprinting: new method for improving accuracy in toric lens orientation.

PMID- 20152623
TI  - Late loss of corneal endothelial density with refractive iris-claw IOLs.

PMID- 20152625
TI  - Consultation section: cataract surgical problem.

PMID- 20152636
TI  - Corneal hysteresis changes in diabetic eyes.

PMID- 20152638
TI  - Chopper and side-port incision leakage.

PMID- 20152639
TI  - Comparison of femtosecond laser and mechanical microkeratome for flap thickness
      accuracy.

PMID- 20152641
TI  - Comparison of fluidics systems of phacoemulsification machines.

PMID- 20152643
TI  - Positioning patients with severe kyphosis during cataract surgery.

PMID- 20152644
TI  - Early publication on intraoperative retinoscopy.

PMID- 20152646
TI  - Black iris-claw intraocular lens for cosmesis.

PMID- 20152647
TI  - Early flap dislocation with perioperative brimonidine use in laser in situ
      keratomileusis.

PMID- 20152649
TI  - Need and demand for orthodontic services: the final report.

PMID- 20152651
TI  - Gnathology lessons from a 1969 Oldsmobile engine.

PMID- 20152652
TI  - After 50 years in practice, the evidence is convincing.

PMID- 20152653
TI  - Myths of orthodontic gnathology.

PMID- 20152654
TI  - Standards of care.

PMID- 20152656
TI  - Validity of 3-dimensional reconstruction and simulation of mandibular movement
      and occlusal contact.

PMID- 20152659
TI  - Postorthodontic root approximation after opening space for maxillary lateral
      incisor implants.
AB  - INTRODUCTION: Orthodontic space opening during adolescence is a common treatment
      for congenitally missing maxillary lateral incisors. Because of continued facial
      growth and compensatory tooth eruption, several years can elapse between
      completion of orthodontic treatment for a teenage patient and implant placement.
      There are reports that, after successful orthodontic opening of the implant
      space, the central incisor and canine roots reapproximate during retention and
      prevent implant placement. METHODS: To study this phenomenon, the records of 94
      patients with missing maxillary lateral incisors were collected. Periapical and
      panoramic radiographs were used to measure intercoronal and interradicular
      distances between the central incisor and the canine adjacent to the missing
      lateral incisor before and after orthodontic treatment and at implant placement.
      RESULTS: Although root approximation between the adjacent central incisor and
      canine during retention did not occur consistently, 11% of the patients
      experienced relapse significant enough to prevent implant placement. CONCLUSIONS:
      To ensure sufficient space for implant placement, we recommend at least 6.3 mm of
      intercoronal space and 5.7 mm of interradicular space between the adjacent
      central incisor and canine. A bonded wire or resin-bonded bridge will help to
      reduce root approximation that might occur during retention.

PMID- 20152661
TI  - Primary failure of eruption and PTH1R: the importance of a genetic diagnosis for
      orthodontic treatment planning.
AB  - INTRODUCTION: Primary failure of eruption (PFE) is characterized by nonsyndromic
      eruption failure of permanent teeth in the absence of mechanical obstruction.
      Recent studies support that this dental phenotype is inherited and that mutations
      in PTH1R genes explain several familial cases of PFE. The objective of our study
      was to investigate how genetic analysis can be used with clinical diagnostic
      information for improved orthodontic management of PFE. METHODS: We evaluated a
      family (n = 12) that segregated an autosomal dominant form of PFE with 5 affected
      and 7 unaffected persons. Nine available family members (5 male, 4 female) were
      enrolled and subsequently characterized clinically and genetically. RESULTS: In
      this family, PFE segregated with a novel mutation in the PTH1R gene. A
      heterozygous c.1353-1 G>A sequence alteration caused a putative splice-site
      mutation and skipping of exon 15 that segregated with the PFE phenotype in all
      affected family members. CONCLUSIONS: A PTH1R mutation is strongly associated
      with failure of orthodontically assisted eruption or tooth movement and should
      therefore alert clinicians to treat PFE and ankylosed teeth with similar caution
      ie, avoid orthodontic treatment with a continuous archwire.

PMID- 20152663
TI  - Engineered cartilage heals skull defects.
AB  - INTRODUCTION: The purposes of this study were to differentiate embryonic limb bud
      cells into cartilage, characterize the nodules produced, and determine their
      ability to heal a mouse skull defect. METHODS: Aggregated mouse limb bud cells
      (E12-E12.5), cultured in a bioreactor for 3 weeks, were analyzed by histology or
      implanted in 6 skull defects. Six controls had no implants. The mice were scanned
      with microcomputed tomography weekly. At 2 and 4 weeks, a mouse from each group
      was killed, and the defect region was prepared for histology. RESULTS:
      Chondrocytes in nodules were mainly hypertrophic. About 90% of the nodules
      mineralized. BrdU staining showed dividing cells in the perichondrium.
      Microcomputed tomography scans showed increasing minerals in implanted nodules
      that completely filled the defect by 6 weeks; defects in the control mice were
      not healed by then. At 2 and 4 weeks, the control skull sections showed only a
      thin bony layer over the defect. At 2 weeks, bone and cartilage filled the
      defects with implants, and the implants were well integrated with the adjacent
      cortical bone. At 4 weeks, the implant had turned almost entirely into bone.
      CONCLUSIONS: Cartilage differentiated in the bioreactor and facilitated healing
      when implanted into a defect. Engineering cartilage to replace bone is an
      alternative to current methods of bone grafting.

PMID- 20152665
TI  - Influence of rapid palatal expansion on maxillary incisor alignment stability.
AB  - INTRODUCTION: The purpose of this retrospective study was to compare the long
      term stability of maxillary incisor alignment in patients treated with and
      without rapid maxillary expansion (RME). METHODS: The sample comprised 48
      subjects with Class I and Class II malocclusions, treated without extractions
      with fixed edgewise appliances, divided into 2 groups according to the treatment
      protocol: group 1 comprised 25 patients (15 girls, 10 boys) at a mean initial age
      of 13.53 years (SD, 1.63), who had RME during orthodontic treatment. Group 2
      comprised 23 patients (13 girls, 10 boys) at a mean initial age of 13.36 years
      (SD, 1.81 years), treated with fixed appliances without RME. Maxillary dental
      cast measurements were obtained at the pretreatment, posttreatment, and long-term
      posttreatment stages. Variables assessed were the irregularity index and
      maxillary arch dimensions. Intergroup comparisons were made with independent t
      tests. RESULTS: Greater transverse increases were found during treatment in the
      group treated with RME. However, during the long-term posttreatment period, no
      significant difference was observed in the amount of incisor crowding relapse
      between the groups. CONCLUSIONS: RME did not influence long-term maxillary
      anterior alignment stability.

PMID- 20152667
TI  - Retrospective cone-beam computed tomography evaluation of temporary anchorage
      devices.
AB  - INTRODUCTION: Miniscrew implants as temporary anchorage devices (TADs) are
      becoming more popular in orthodontic treatment. Their ease of use allows
      orthodontists to place them in locations in the mouth that are convenient for
      orthodontic treatment mechanics. The aims of this study were to evaluate the
      location of TADs placed during orthodontic treatment and to relate the placement
      to the surrounding dentoalveolar structures. METHODS: Three-dimensional cone-beam
      computed tomography scans were taken before and after placement of the TADs over
      a 6-month period as part of routine clinical protocol. The following parameters
      were recorded: placement site, length of the TAD in the alveolar bone, amount of
      contact with the periodontal ligament, and interroot distance between TADs.
      RESULTS: Thirty-five TADs (19 in the maxilla, 16 in the mandible) were evaluated.
      The mean lengths of the TADs in alveolar bone were 5.29 +/- 1.39 mm in the
      maxilla and 4.60 +/- 0.86 mm in the mandible. The amounts of contact with the
      periodontal ligaments were 2.54 +/- 0.81 mm (n = 13) in the maxilla and 2.72 +/-
      0.49 mm (n = 10) in the mandible. The interroot distance measurements were 2.78
      +/- 0.76 mm (n = 15) and 5.19 +/- 4.42 mm (n = 16) in the maxilla and the
      mandible, respectively. Paired t tests indicated a significant difference in the
      interroot distance for mandibular teeth. CONCLUSIONS: Three-dimensional cone-beam
      computed tomography technology allows better visualization of TAD placement.
      Clinicians can expect 71.2% of the length of the screw section of the TAD to be
      embedded in the alveolar bone; the percentage is often higher in the maxilla than
      in the mandible. Of the 35 TADs, 65.2% were in contact with the periodontal
      ligament. There appears to be more space for TAD placement in the mandible than
      in the maxilla.

PMID- 20152669
TI  - Impact of facial asymmetry in visual perception: a 3-dimensional data analysis.
AB  - INTRODUCTION: The aim of this controlled study was to analyze the degree and
      localization of 3-dimensional (3D) facial asymmetry in adult patients with cleft
      lip and palate (CLP) compared with a control group and its impact on the visual
      perception of faces. METHODS: The degree of 3D asymmetry was analyzed with a
      novel method without landmarks in 18 adults with complete unilateral CLP and 18
      adults without congenital anomalies. Furthermore, the CLP and control faces were
      rated for appearance, symmetry, and facial expression by 30 participants.
      RESULTS: The results showed that adults with CLP had significantly greater
      asymmetry in their facial soft tissues compared with the control group. Moreover,
      the lower face, and particularly the midface, had greater asymmetry in the CLP
      patients. The perceptual ratings showed that adults with CLP were judged much
      more negatively than those in the control group. CONCLUSIONS: With sophisticated
      3D analysis, the real morphology of a face can be calculated and asymmetric
      regions precisely identified. The greatest asymmetry in CLP patients is in the
      midface. These results underline the importance of symmetry in the perception of
      faces. In general, the greater the facial asymmetry near the midline of the face,
      the more negative the evaluation of the face in direct face-to-face interactions.

PMID- 20152670
TI  - Results of a survey-based study to identify common retention practices in the
      United States.
AB  - INTRODUCTION: The purpose of this descriptive study was to use a carefully
      constructed, pilot-tested survey instrument to identify the most common
      orthodontic retainers and retention protocols prescribed in the United States as
      reported by active members of the American Association of Orthodontists. METHODS:
      We randomly selected 2000 active members, stratified by region of practice, for
      the study. Information gathered included, but was not limited to, the types of
      retainers prescribed in the maxillary and mandibular arches, duration of full
      time and part-time wear, use of fixed retainers, appliances fabricated in office
      vs commercial laboratories, the number of debonds per year, and retention
      appointment schedules. The survey consisted of 20 questions. Data were gathered
      on a categorical scale and analyzed. RESULTS: We received 658 responses (32.9%)
      during a 12-week period. Maxillary Hawley retainers (58.2%) and mandibular fixed
      lingual retainers (40.2%) were the most commonly used. Most orthodontists
      prescribed less than 9 months of full-time wear of removable retainers and
      thereafter advised part-time, but lifetime wear. Most orthodontists (75.9%) did
      not instruct patients to have the fixed lingual retainers removed at a specific
      time. More orthodontists who prescribed Hawley retainers recommended longer full
      time wear compared with clear thermoplastic retainers. The timing of scheduled
      retention appointments varied among clinicians and depended on the number of
      years in practice, the volume of patients debonded, and the type of prescribed
      retainer. The only regional difference associated with retainer design was the
      Northeast region, where mandibular fixed lingual retainers were used less
      frequently. Female orthodontists did not use mandibular fixed lingual retainers
      as often as their male counterparts. CONCLUSIONS: Maxillary Hawley and mandibular
      fixed lingual retainers are most commonly used. This study is the first to
      describe retention protocols and the scheduling of retention appointments in the
      United States.

PMID- 20152672
TI  - Pretreatment characteristics associated with orthodontic treatment duration.
AB  - INTRODUCTION: Pretreatment characteristics can assist orthodontists in accurately
      estimating treatment duration. METHODS: This case-control study identified 400
      patients, 9 to 18 years of age. Short treatment duration was 20 months or less,
      and long treatment duration was 30 months or longer. Potential pretreatment
      explanatory variables included planned treatment, sociodemographic, behavior,
      dental, skeletal, and soft-tissue characteristics. Univariable and multivariable
      logistic regression modeling was used to quantify the association between patient
      characteristics and treatment duration by reporting the unadjusted odds ratios
      (ORcrude), the adjusted odds ratios (ORadj), and the 95% confidence intervals
      (CIs). RESULTS: Patients planned as nonextraction (ORadj = 2.3; 95% CI, 1.3-4.2),
      no deciduous teeth (ORadj = 3.0; 95% CI, 1.5-5.9), less than 80% overbite (ORadj
      = 2.4; 95% CI, 1.3-4.4), less than 6 mm of maxillary crowding (ORadj = 3.6; 95%
      CI, 1.7-7.7), and good oral hygiene (ORadj = 3.2; 95% CI, 1.3-1.8) were 2 to 3
      times more likely to have short treatments. Patients with decreased lower facial
      height (ORadj = 3.4; 95% CI, 1.6-7.1), extractions (ORadj = 1.8; 95% CI, 1.0
      3.2), deciduous teeth (ORadj = 1.9; 95% CI, 1.0-3.4), poor grades (ORadj = 2.0;
      95% CI, 1.1-3.8), excessive overjet (ORadj = 2.3; 95% CI, 1.4-3.8), 80% or more
      overbite (ORadj = 2.0; 95% CI,1.2-3.6), and 6 mm or more of maxillary crowding
      (ORadj = 2.6; 95% CI,1.4-4.6) were 2 to 3 times more likely to have long
      treatments. CONCLUSIONS: Presence or absence of severe maxillary crowding,
      deciduous teeth, 80% overbite, and extractions were consistently, inversely, and
      independently associated with short and long treatment durations.

PMID- 20152673
TI  - Longitudinal changes in mandibular arch posterior space in adolescents with
      normal occlusion.
AB  - INTRODUCTION: The purpose of this study was to investigate the changes of
      available mandibular space in the posterior dental arch of teenagers from 13 to
      18 years old. METHODS: Longitudinal cephalograms of 28 adolescents (13 boys, 15
      girls) with normal occlusion, selected from among 901 candidates, were taken
      annually from 13 to 18 years of age inclusively. Modified analyses with occlusal
      plane and occlusal plane perpendicular as reference planes were used to evaluate
      the changes of available space of the posterior mandibular arch. RESULTS: From 13
      to 18 years of age, significant differences of mandibular posterior space were
      found among ages and sexes. The total increases of available space were 5.12 mm
      in the girls and 5.79 mm in the boys. For girls before age 16 and boys before age
      17, the increased available space was contributed mainly by resorption of bone on
      the anterior border of the ramus. Mesial drift of the dental arch did not occur
      until the eruption of the third molars. The average available spaces increased
      1.22 mm in girls less than age 16 and 1.45 mm in boys less than age 17 per side
      per year. CONCLUSIONS: The prediction of available space in the posterior
      mandibular arch should be based on age and sex.

PMID- 20152674
TI  - Survival analysis of orthodontic mini-implants.
AB  - INTRODUCTION: Survival analysis is useful in clinical research because it focuses
      on comparing the survival distributions and the identification of risk factors.
      Our aim in this study was to investigate the survival characteristics and risk
      factors of orthodontic mini-implants with survival analyses. METHODS: One hundred
      forty-one orthodontic patients (treated from October 1, 2000, to November 29,
      2007) were included in this survival study. A total of 260 orthodontic mini
      implants that had sandblasted (large grit) and acid-etched screw parts were
      placed between the maxillary second premolar and the first molar. Failures of the
      implants were recorded as event data, whereas implants that were removed because
      treatment ended and those that were not removed during the study period were
      recorded as censored data. A nonparametric life table method was used to
      visualize the hazard function, and Kaplan-Meier survival curves were generated to
      identify the variables associated with implant failure. Prognostic variables
      associated with implant failure were identified with the Cox proportional hazard
      model. RESULTS: Of the 260 implants, 22 failed. The hazard function for implant
      failure showed that the risk is highest immediately after placement. The survival
      function showed that the median survival time of orthodontic mini-implants is
      sufficient for relatively long orthodontic treatments. The Cox proportional
      hazard model identified that increasing age is a decisive factor for implant
      survival. CONCLUSIONS: The decreasing pattern of the hazard function suggested
      gradual osseointegration of orthodontic mini-implants. When implants are placed
      in a young patient, special caution is needed to lessen the increased probability
      of failure, especially immediately after placement.

PMID- 20152675
TI  - Proper mesiodistal angles for microimplant placement assessed with 3-dimensional
      computed tomography images.
AB  - INTRODUCTION: To provide information about placement sites and angulations of
      microimplants between tooth roots, we analyzed 3-dimensional computed tomography
      images from 25 patients. METHODS: The patients in the sample had good
      interdigitation, no restorations, and no arch length discrepancies in the
      posterior segments. Three-dimensional images of the maxillary and mandibular
      second premolars, first molars, and second molars were constructed. The distances
      and midpoints between the roots at 3 levels were calculated, and the angles
      between the lines connecting the midpoints and perpendicular lines to the
      occlusal plane at the contact points were also calculated. RESULTS: The midpoints
      between the roots were located distally to the contact point and from the
      cervical to the apical areas. The lines connecting these midpoints from the
      cervix to the apex of the roots in the mandibular arch had more distal
      inclination than in the maxillary arch. CONCLUSIONS: To minimize root contacts,
      microimplants need to be inclined distally about 10 degrees to 20 degrees and
      placed 0.5 to 2.7 mm distally to the contact point to minimize root contact
      according to sites and levels, except into palatal interradicular bone between
      the maxillary first and second molars.

PMID- 20152676
TI  - Apical root resorption in orthodontic patients with en-masse maxillary anterior
      retraction and intrusion with miniscrews.
AB  - INTRODUCTION: The purposes of this retrospective study were to investigate the
      apical root resorption of maxillary incisors in orthodontic patients with en
      masse maxillary anterior retraction and intrusion with miniscrews and the factors
      disposing a patient to apical root resorption. METHODS: Fifty adult patients with
      maxillary protrusion were included; 30 were treated with miniscrews and
      extraction of the maxillary first premolars (group I), and 20 were treated with
      extraction of the maxillary first premolars (group II). For each patient,
      periapical films of the maxillary incisors and lateral cephalometric radiographs
      were taken before and after treatment to evaluate apical root resorption and
      cephalometric measurements. The intergroup differences were analyzed with the
      Student t test and the correlations between apical root resorption and
      cephalometric measurements were analyzed by the Pearson correlation. RESULTS: The
      apical root resorption values were 16.0% to 20.0% (2.5-2.8 mm) in group I and
      13.4% to 14.4% (2.1-2.3 mm) of the original root length in group II. Group I had
      significantly more severe Class II jaw discrepancy (ANB, 7.1 degrees +/- 1.9
      degrees ) than did group II (ANB, 3.2 degrees +/- 2.9 degrees ). The amount of
      maxillary en-masse anterior retraction (8.2 +/- 2.4 mm), the duration of
      treatment (28.3 +/- 7.3 months), and apical root resorption of maxillary lateral
      incisors were significantly greater in group I than in group II. Apical root
      resorption of the maxillary central incisors was significantly correlated to the
      duration of treatment but not to the amount of en-masse retraction, intrusion, or
      palatal tipping of maxillary incisors. CONCLUSIONS: Miniscrew anchorage allows
      for more maxillary en-masse anterior retraction in patients with severe Class II
      cases. But the time needed for the greater amount of maxillary en-masse anterior
      retraction with miniscrew anchorage is longer and might dispose the patient to
      more apical root resorption.

PMID- 20152677
TI  - Mechanical properties of coated superelastic archwires in conventional and self
      ligating orthodontic brackets.
AB  - INTRODUCTION: Coated archwires have been introduced to improve esthetics during
      orthodontic treatment. Our aim was to investigate the mechanical properties of
      coated superelastic archwires compared with conventional superelastic archwires
      with conventional and self-ligating brackets. METHODS: Four types of orthodontic
      archwires were investigated, 2 superelastic nickel-titanium and 2 coated
      Ultraesthetic archwires in 0.016-in and 0.018 x 0.025-in dimensions (all from G&H
      Wire, Greenwood, Ind). To achieve the same nominal size, the coated archwire is
      constructed from a smaller archwire that, when coated, reaches the nominal
      dimensions stated for the archwire. Conventional edgewise Orthos and Damon 2 self
      ligating brackets (both from Ormco, Orange, Calif) were used with each wire. All
      specimens were tested in a universal testing machine in a 3-point bending test at
      a speed of 1 mm per minute and deflected for 2 mm. Loading and unloading forces
      were recorded and load-deflection curves plotted. RESULTS: Coated superelastic
      wires produced statistically significantly lower forces in loading and unloading
      when compared with the superelastic nickel-titanium wires at most archwire
      deflections (P <0.01). For nickel-titanium wires, loading values ranged from 189
      to 1202 g, whereas the respective values for coated wires were 124 to 772 g. For
      all wires, an increase in size resulted in an increase in force. Interactions
      between wire type (coated or uncoated) and bracket type were observed.
      CONCLUSIONS: Ultraesthetic coated archwires produced lower force values in
      loading and unloading compared with uncoated wires of same nominal size. The
      Damon 2 self-ligating bracket system produced lower force values in loading and
      unloading. The lowest forces were generated by the combination of Ultraesthetic
      coated archwires and Damon 2 self-ligating brackets.

PMID- 20152678
TI  - Morphologic quantification of the maxilla and the mandible with cone-beam
      computed tomography.
AB  - INTRODUCTION: The purpose of this pilot study was to use cone-beam computed
      tomography (CBCT) to determine the volumes of the maxilla and the mandible in
      subjects with skeletal Class I, Class II, and Class III malocclusions. Hypothesis
      1 was that the volume (size) of a skeletal Class II maxilla is larger than those
      of Class I and Class III. Hypothesis 2 was that the volume of a skeletal Class
      III mandible is larger than those of Class I and Class II. METHODS: Thirty women
      patients were classified into 3 groups according to their skeletal pattern:
      skeletal Class I (0 degrees < or =ANB <6 degrees ), Class II (ANB > or =6 degrees
      ) and Class III (ANB <0 degrees ). The volumes of the maxilla and the mandible
      were measured with CBCT. CB MercuRay (Hitachi Medico, Tokyo, Japan) and CB works
      software (CyberMed, Seoul, Korea) were used to process the images. RESULTS: There
      was a trend that skeletal Class III subjects might have significantly greater
      mandibular volume compared with Class II subjects (P = 0.089). The ratios of
      maxilla-to-mandible volumes between the skeletal Class II and Class III groups
      were significantly different (P = 0.005). Differences were observed in the ratios
      of maxillary and mandibular volumes across the 3 groups. CONCLUSIONS: Hypotheses
      1 and 2 were rejected; there was no trend for Class III subjects to have larger
      mandibles (P = 0.089) compared with Class II subjects. The ratio of the maxilla
      and mandible volumes in skeletal Class III subjects was significantly larger (P =
      0.005) compared with Class II subjects.

PMID- 20152679
TI  - Clinical and microbiological findings at sites treated with orthodontic fixed
      appliances in adolescents.
AB  - INTRODUCTION: Fixed orthodontic appliances can alter the subgingival microbiota.
      Our aim was to compare the subgingival microbiota and clinical parameters in
      adolescent subjects at sites of teeth treated with orthodontic bands with margins
      at (OBM) or below the gingival margin (OBSM), or with brackets (OBR). METHODS:
      Microbial samples were collected from 33 subjects (ages, 12-18 years) in
      treatment more than 6 months. The microbiota was assessed by the DNA-DNA
      checkerboard hybridization method. RESULTS: Bacterial samples were taken from 83
      OBR,103 OBSM, and 54 OBM sites. Probing pocket depths differed by orthodontic
      type (P <0.001) with mean values of 2.9 mm (SD, 0.6) at OBSM sites, 2.5 mm (SD,
      0.6) at OBM sites, and 2.3 mm (SD, 0.5) at OBR sites. Only Actinomyces israelii
      (P <0.001) and Actinomyces naeslundii (P <0.001) had higher levels at OBR sites,
      whereas Neisseria mucosa had higher levels at sites treated with OBSM or OBM (P
      <0.001). Aggregatibacter actinomycetemcomitans was found in 25% of sites
      independent of the appliance. CONCLUSIONS: Different types of orthodontic
      appliances cause minor differences in the subgingival microbiota (A israelii and
      A naeslundii) and higher levels at sites treated with orthodontic brackets. More
      sites with bleeding on probing and deeper pockets were found around orthodontic
      bands.

PMID- 20152680
TI  - Effects of ultrasonic, electric, and manual toothbrushes on subgingival plaque
      composition in orthodontically banded molars.
AB  - INTRODUCTION: Orthodontic appliances hinder mechanical plaque control. In this
      study, we evaluated the effect of self-performed supragingival plaque removal
      with ultrasonic, electric, and manual toothbrushes on subgingival plaque
      composition in orthodontically banded molars. METHODS: Twenty-one patients
      wearing fixed orthodontic appliances were assigned to this single-blind crossover
      study. Samples of subgingival plaque were collected from banded molars, before
      and after each toothbrush usage period, for quantification of 22 bacterial
      species by the checkerboard DNA-DNA hybridization method. For each crossover,
      patients used a toothbrush for 30 days, followed by a washout period of 14 days.
      RESULTS: The prevalence of Tannerella forsythia decreased significantly after a
      month of electric brush usage. In the manual brush group, the prevalences of
      Selenomonas noxia, Streptococcus sanguinis, and Prevotella melaninogenica also
      decreased significantly. However, there were no significant differences in the
      prevalences and levels of bacteria after usage of the ultrasonic brush.
      Intergroup comparisons showed no statistical differences among the 3 brushes for
      the microbiologic parameters. CONCLUSIONS: All 3 brushes generally reduced
      bacterial prevalences, and, although electric and manual toothbrushes showed some
      isolated significant variations, we found no superiority with any toothbrush type
      when used three times daily for 2 minutes on microbiologic parameters in
      orthodontically banded molars.

PMID- 20152681
TI  - Cephalometric and electromyographic study of patients of East African ethnicity
      with and without anterior open bite.
AB  - INTRODUCTION: A review of the literature showed that there are disturbances of
      muscle activity and tongue function in patients with anterior open bite (AOB).
      However, most studies have had white subjects, even though open bite is more
      prevalent in black populations. In this pilot study, we examined jaw muscle
      activity and tongue pressure in East African black subjects. METHODS: Ten
      subjects (4 boys, 6 girls; ages, 10.1-13.2 years) were recruited. A cephalometric
      comparison of subjects with and without AOB was performed. Surface electrodes
      were placed on the bilateral anterior temporalis, superficial masseter, superior
      orbicularis oris, and anterior digastric muscles. Electromyograms were recorded
      at rest, maximal voluntary clenching, chewing, and swallowing. Tongue pressure
      during rest and swallowing, and maximal bite force were also measured. RESULTS:
      There was no statistically significant difference between the 2 groups in
      cephalometric measures (except in amount of open bite and overbite) and maximum
      bite force. During chewing, both groups showed similar coordinated activity
      patterns in the muscles, but the AOB subjects tended to show more
      electromyographic activity in the muscles of the balancing side. During
      clenching, the AOB subjects exhibited lower electromyographic activity compared
      with the controls. AOB subjects also had greater anterior tongue pressure during
      swallowing. Data from tongue pressure at rest were inconclusive. CONCLUSIONS:
      East African blacks appear to have neuromuscular and skeletal predispositions to
      AOB, but their vertical incisor relationships are variable. Factors in addition
      to those investigated might be involved.

PMID- 20152682
TI  - In-vitro study of the cellular viability and nitric oxide production by J774
      macrophages with ceramic, polycarbonate, and polyoxymethylene brackets.
AB  - INTRODUCTION: Studies show that ceramic brackets are chemically inert in the oral
      cavity, whereas polycarbonate and polyoxymethylene brackets can degrade,
      releasing bisphenol-A and formaldehyde, respectively. In addition to the
      traditional cytotoxicity tests, the study of nitric oxide cellular production
      stimulated by a specific material has been shown to be a reliable tool for
      evaluating its cytotoxic potential. METHODS: We aimed to assess cellular
      viability by MTT (Sigma, St. Louis, Mo): 3,(4,5-dimethylthiazol-2-yl)-2,5diphenyl
      tetrazolium bromide assay in a murine macrophage cell line J774 with esthetic
      brackets and quantify nitric oxide production by these macrophages. Cell cultures
      were evaluated at 3 times: 24, 48, and 72 hours. RESULTS: Cellular viability in
      all groups was higher at 72 hours compared with 24 hours. This increase was
      significant in the control and ceramic brackets groups. Final means in the
      bracket groups showed no significant differences compared with the control group.
      Nitric oxide production was significantly greater in all groups at final time.
      There was no significant difference between the final means of the bracket groups
      and the control group, although polyoxymethylene brackets showed significantly
      greater means at 24 and 48 hours. CONCLUSIONS: Final means in the bracket groups
      showed no significant differences compared with the control group.

PMID- 20152683
TI  - Pulp vitality after rapid palatal expansion.
AB  - INTRODUCTION: Although it has been suggested that orthodontic treatment might
      lead to changes in the dental pulp, no clinical study has attempted to
      investigate the incidence of pulp necrosis after orthodontic therapy. The purpose
      of this clinical trial was to determine whether pulp testing response is altered
      after rapid palatal expansion (RPE). METHODS: Twenty-five adolescent patients (9
      boys, 16 girls; ages, 10-16 years) participated in the study. A hyrax appliance
      was cemented on the first permanent molars and first premolars (when fully
      erupted). The appliance was activated twice daily (0.5 mm) for 2 weeks. An
      electric pulp tester (EPT) was used to test at the buccal cusp tips of the molars
      and premolars. Teeth that did not respond to the EPT were subsequently tested
      thermally with Endo Ice (Hygienic Corporation, Akron, Ohio). RESULTS: All
      maxillary molars and erupted premolars of the 25 patients responded positively to
      pulp tests before cementation of the hyrax appliance. Of the 49 molars tested, 46
      responded positively to the EPT, and 3 responded positively to the cold testing
      (CT). Of the 42 first premolars tested, 40 responded positively to the EPT and 2
      to the CT. Of the 38 second premolars tested, 35 responded positively to the EPT
      and 3 to the CT. Two weeks after the initial activation of the hyrax appliance,
      93 teeth in 17 subjects were tested. Of the 93 teeth, 73 teeth responded
      positively to the EPT and 20 to the CT. Three to 6 weeks after hyrax activation
      was discontinued, 59 teeth were tested; 48 tested positively to the EPT and 10 to
      the CT. One tooth (maxillary left first molar) did not respond to either EPT or
      CT. Finally, 3 to 9 months into retention, all molars and premolars of 23
      subjects tested positive to pulp tests, 92 teeth to the EPT and 25 to the CT. The
      maxillary left first molar that had not responded to the tests at the 3-to-6 week
      check responded positively to the CT at the final check. CONCLUSIONS: After RPE
      therapy in children and adolescents, the pulp of the posterior permanent teeth
      examined in this study was vital.

PMID- 20152684
TI  - Three-dimensional dental measurements: An alternative to plaster models.
AB  - INTRODUCTION: The aim of this study was to compare the accuracy of dental
      measurements taken with calipers on plaster dental casts and those from computed
      tomography scans of the dentition with a dental measurement program. METHODS: The
      sample consisted of plaster dental models of 34 orthodontic subjects. Dental arch
      measurements, including mesiodistal widths of teeth, arch widths, arch lengths,
      arch perimeters, and palatal depths were made with the calipers. The patients
      were also scanned with computed tomography, and measurements were made digitally
      with a 3-dimensional-based dental measurements program (3DD, Biodent, Cairo,
      Egypt). RESULTS: The results showed strong agreement in most measurements between
      the conventional method and the 3DD in the 3 planes of space. The mesiodistal
      measurements of the maxillary right and left second premolars, left central
      incisor, and right first molar, and the mandibular left and right central
      incisors, right canine, and left first premolar had fair agreement. CONCLUSIONS:
      Excellent agreement between the measurements with the conventional and 3DD
      methods in the 3 planes of space was found; 3DD can be an alternative to
      conventional stone dental models.

PMID- 20152685
TI  - Methods for managing 3-dimensional volumes.
AB  - The introduction of 3-dimensional (3D) volumetric technology and the massive
      amount of information that can be obtained from it compels the introduction of
      new methods and new technology for orthodontic diagnosis and treatment planning.
      In this article, methods and tools are introduced for managing 3D images of
      orthodontic patients. These tools enable the creation of a virtual model and
      automatic localization of landmarks on the 3D volumes. They allow the user to
      isolate a targeted region such as the mandible or the maxilla, manipulate it, and
      then reattach it to the 3D model. For an integrated protocol, these procedures
      are followed by registration of the 3D volumes to evaluate the amount of work
      accomplished. This paves the way for the prospective treatment analysis approach,
      analysis of the end result, subtraction analysis, and treatment analysis.

PMID- 20152687
TI  - Mandibular "tripod" advancement of a Class II Division 2 deepbite malocclusion.
AB  - This case report describes the treatment of a 25-year-old woman with a Class II
      malocclusion, secondary to mandibular skeletal deficiency, and mild overclosure.
      Inferior surgical repositioning of the maxilla is often the treatment of choice
      for patients with maxillary vertical deficiency; however, this patient had
      borderline vertical deficiency that was treated with a mandibular "tripod"
      advancement (leveling of the mandibular arch after surgery) coupled with a
      setback and down-grafting genioplasty. The surgical-orthodontic treatment plan,
      combined with cosmetic dentistry, resulted in dramatically improved facial
      esthetics and occlusal relationships.

PMID- 20152686
TI  - Three-dimensional analysis of maxillary protraction with intermaxillary elastics
      to miniplates.
AB  - INTRODUCTION: Early Class III treatment with reverse-pull headgear generally
      results in maxillary skeletal protraction but is frequently also accompanied by
      unfavorable dentoalveolar effects. An alternative treatment with intermaxillary
      elastics from a temporary anchorage device might permit equivalent favorable
      skeletal changes without the unwanted dentoalveolar effects. METHODS: Six
      consecutive patients (3 boys, 3 girls; ages, 10-13 years 3 months) with Class III
      occlusion and maxillary deficiency were treated by using intermaxillary elastics
      to titanium miniplates. Cone-beam computed tomography scans taken before and
      after treatment were used to create 3-dimensional volumetric models that were
      superimposed on nongrowing structures in the anterior cranial base to determine
      anatomic changes during treatment. RESULTS: The effect of the intermaxillary
      elastic forces was throughout the nasomaxillary structures. All 6 patients showed
      improvements in the skeletal relationship, primarily through maxillary
      advancement with little effect on the dentoalveolar units or change in mandibular
      position. CONCLUSIONS: The use of intermaxillary forces applied to temporary
      anchorage devices appears to be a promising treatment method.

PMID- 20152689
TI  - Lest we forget the patients!

PMID- 20152690
TI  - Governmental regulation and impact on reimbursement for vascular imaging: a need
      for active participation.

PMID- 20152691
TI  - Reference values for right ventricular volumes and ejection fraction with real
      time three-dimensional echocardiography: evaluation in a large series of normal
      subjects.
AB  - BACKGROUND: The quantification of right ventricular (RV) size and function is of
      diagnostic and prognostic importance. Recently, new software for the analysis of
      RV geometry using three-dimensional (3D) echocardiographic images has been
      validated. The aim of this study was to provide normal reference values for RV
      volumes and function using this technique. METHODS: A total of 245 subjects,
      including 15 to 20 subjects for each gender and age decile, were studied.
      Dedicated 3D acquisitions of the right ventricle were obtained in all subjects.
      RESULTS: The mean RV end-diastolic and end-systolic volumes were 49 +/- 10 and 16
      +/- 6 mL/m2 respectively, and the mean RV ejection fraction was 67 +/- 8%.
      Significant correlations were observed between RV parameters and body surface
      area. Normalized RV volumes were significantly correlated with age and gender. RV
      ejection fractions were lower in men, but differences across age deciles were not
      evident. CONCLUSION: The current study provides normal reference values for RV
      volumes and function that may be useful for the identification of clinical
      abnormalities.

PMID- 20152692
TI  - Dynamic assessment of right ventricular volumes and function by real-time three
      dimensional echocardiography: a comparison study with magnetic resonance imaging
      in 100 adult patients.
AB  - BACKGROUND: The aim of this study was to validate a novel real-time three
      dimensional echocardiographic (RT3DE) analysis tool for the determination of
      right ventricular volumes and function in unselected adult patients. METHODS: A
      total of 100 consecutive adult patients with normal or pathologic right
      ventricles were enrolled in the study. A dynamic polyhedron model of the right
      ventricle was generated using dedicated RT3DE software. Volumes and ejection
      fractions were determined and compared with results obtained on magnetic
      resonance imaging (MRI) in 88 patients with adequate acquisitions. RESULTS: End
      diastolic, end-systolic, and stroke volumes were slightly lower on RT3DE imaging
      than on MRI (124.0 +/- 34.4 vs 134.2 +/- 39.2 mL, P < .001; 65.2 +/- 23.5 vs 69.7
      +/- 25.5 mL, P = .02; and 58.8 +/- 18.4 vs 64.5 +/- 24.1 mL, P < .01,
      respectively), while no significant difference was observed for ejection fraction
      (47.8 +/- 8.5% vs 48.2 +/- 10.8%, P = .57). Correlation coefficients on Bland
      Altman analysis were r = 0.84 (mean difference, 10.2 mL; 95% confidence interval
      [CI], -31.3 to 51.7 mL) for end-diastolic volume, r = 0.83 (mean difference, 4.5
      mL; 95% CI, -23.8 to 32.9 mL) for end-systolic volume, r = 0.77 (mean difference,
      5.7 mL; 95% CI, -24.6 to 36.0 mL) for stroke volume, and r = 0.72 (mean
      difference, 0.4%; 95% CI, -14.2% to 15.1%) for ejection fraction. CONCLUSION:
      Right ventricular volumes and ejection fractions as assessed using RT3DE imaging
      compare well with MRI measurements. RT3DE imaging may become a time-saving and
      cost-saving alternative to MRI for the quantitative assessment of right
      ventricular size and function.

PMID- 20152693
TI  - Clinical value of real-time three-dimensional echocardiography for right
      ventricular quantification in congenital heart disease: validation with cardiac
      magnetic resonance imaging.
AB  - BACKGROUND: The objective of this study was to test the feasibility, accuracy,
      and reproducibility of the assessment of right ventricular (RV) volumes and
      ejection fraction (EF) using real-time three-dimensional echocardiographic
      (RT3DE) imaging in patients with congenital heart disease (CHD), using cardiac
      magnetic resonance (CMR) as a reference. METHODS: RT3DE data sets and short-axis
      cine CMR images were obtained in 62 consecutive patients (mean age, 26.9 +/- 10.4
      years; 65% men) with various CHDs. RV volumetric quantification was done using
      semiautomated 3-dimensional border detection for RT3DE images and manual tracing
      of contours in multiple slices for CMR images. RESULTS: Adequate RV RT3DE data
      sets could be analyzed in 50 of 62 patients (81%). The time needed for RV
      acquisition and analysis was less for RT3DE imaging than for CMR (P < .001).
      Compared with CMR, RT3DE imaging underestimated RV end-diastolic and end-systolic
      volumes and EF by 34 +/- 65 mL, 11 +/- 55 mL, and 4 +/- 13% (P < .05) with 95%
      limits of agreement of +/-131 mL, +/-109 mL, and +/-27%, as shown by Bland-Altman
      analyses, with highly significant correlations (r = 0.93, r = 0.91, and r = 0.74,
      respectively, P < .001). Interobserver variability was 1 +/- 15%, 6 +/- 17%, and
      8 +/- 13% for end-diastolic and end-systolic volumes and EF, respectively.
      CONCLUSION: In the majority of unselected patients with complex CHD, RT3DE
      imaging provides a fast and reproducible assessment of RV volumes and EF with
      fair to good accuracy compared with CMR reference data when using current
      commercially available hardware and software. Further studies are warranted to
      confirm our data in similar and other patient populations to establish its use in
      clinical practice.

PMID- 20152694
TI  - Imaging the forgotten chamber: is the devil in the boundary?

PMID- 20152695
TI  - Patent foramen ovale: echocardiographic detection and clinical relevance in
      stroke.
AB  - This article reviews the main clinical aspects of patent foramen ovale (PFO),
      such as its prevalence in the population, the diagnostic techniques to detect its
      presence, its role as a risk factor for ischemic stroke of otherwise unexplained
      origin, and its controversial association with migraine. Some cofactors possibly
      involved in the association between PFO and stroke are discussed, along with the
      various therapeutic options to prevent recurrent cerebral ischemic events in
      stroke patients with a PFO.

PMID- 20152696
TI  - Do additional echocardiographic variables increase the accuracy of E/e' for
      predicting left ventricular filling pressure in normal ejection fraction? An
      echocardiographic and invasive hemodynamic study.
AB  - BACKGROUND: There are few data on adding left atrial volume index (LAVi) or
      pulmonary artery systolic pressure (PAP) to the ratio of early mitral inflow to
      mitral annular velocity (E/e') for the estimation of left ventricular (LV)
      filling pressure in patients with preserved LV ejection fractions (LVEFs) (>50%).
      METHODS: Patients underwent echocardiography within 20 minutes of cardiac
      catheterization. Echocardiographic variables were compared with invasively
      measured LV preatrial contraction pressure (pre-A). RESULTS: Of the 122 patients
      studied (mean age, 55 +/- 9 years; mean LVEF, 61 +/- 6%), 67 (55%) were women,
      108 (88%) had hypertension, and 79 (65%) had significant coronary artery disease
      at catheterization. E/e' was significantly correlated with pre-A (R = 0.63, P <
      .0001) compared with LAVi (R = 0.49, P < .001) and PAP (R = 0.48, P < .001). E/e'
      > 13 had sensitivity of 70% and specificity of 93% (area under the curve [AUC],
      0.82; P < .0001), LAVi > 31 mL/m2 had sensitivity of 78% and specificity of 76%
      (AUC, 0.80, P < .001), and PAP > 28 mm Hg had sensitivity of 80% and specificity
      of 64% for pre-A > 15 mm Hg (AUC, 0.77, P < .001). Adding LAVi >31 mL/m2 for E/e'
      = 8 to 13 significantly increased the accuracy of E/e' > 13 alone (sensitivity,
      87%; specificity, 88%; AUC, 0.89; P = .01 for comparison). However, adding PAP >
      28 mm Hg for E/e' = 8 to 13 did not significantly increase the accuracy of E/e' >
      13 alone (AUC, 0.82; sensitivity, 82%; specificity, 72%; P = NS for comparison).
      CONCLUSIONS: In patients with preserved LVEFs, adding LAVi > 31 mL/m2 to E/e'
      (when E/e' was in the gray zone, but not when E/e' was >13) significantly
      increased the accuracy of E/e' alone for the estimation of LV filling pressure.
      These data support the notion of using several, rather than any single, Doppler
      echocardiographic parameter for the accurate assessment of LV diastolic function.

PMID- 20152697
TI  - Diagnosing left ventricular diastolic dysfunction by echocardiography: Reverend
      Bayes lends a hand.

PMID- 20152698
TI  - Diastolic myocardial mechanics in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by myocardial
      hypertrophy, fiber disarray, and fibrosis interfering with myocardial force
      generation and relaxation. Because conventional Doppler echocardiographic methods
      inadequately assess diastolic function in HCM, the aim of this study was to
      determine local and global left ventricular (LV) relaxation mechanics in patients
      with HCM. METHODS: Seventy-two patients with HCM and 32 normal controls were
      studied. Using Velocity Vector Imaging, longitudinal and circumferential strain,
      strain rate, and rotation at the base, middle, and apex of the septal and lateral
      LV walls were measured. Differences between patients' functional class subgroups
      were assessed using analysis of variance, and Tukey's post hoc analysis was used
      to compare patients in HCM clinical subgroups with normal controls. RESULTS:
      Longitudinal strain and systolic and early diastolic strain rates were lower than
      normal in patients with HCM, whereas their circumferential values were higher.
      This suggests that shortening and relaxation orientation in HCM was more
      circumferential. The ratio of peak early diastolic to peak systolic strain rate
      decreased longitudinally and circumferentially in moderately to severely
      symptomatic (New York Heart Association class III or IV) patients (0.95 +/- 0.35
      vs 0.89 +/- 0.35, P < .001). LV untwist was similarly prolonged in all HCM
      subgroups. LV relaxation assessed using the early apical reverse rotation
      fraction was significantly lower in patients with worse functional status (34 +/-
      14% vs 18 +/- 4% in class I or II vs class III or IV). Left atrial volume
      increased, paralleling the severity of symptoms and the degree of diastolic
      dysfunction. CONCLUSIONS: The evaluation of biplane myocardial mechanics offers
      new insights into the evaluation of diastolic function and its relationship to
      clinical status.

PMID- 20152699
TI  - Left atrial strain measured by two-dimensional speckle tracking represents a new
      tool to evaluate left atrial function.
AB  - BACKGROUND: Left atrial (LA) strain (epsilon) and epsilon rate (SR) analysis by
      two-dimensional speckle tracking can represent a new tool to evaluate LA
      function. To assess its potential value, the authors addressed whether LA epsilon
      and SR measured in normal subjects correlates with other Doppler
      echocardiographic parameters that evaluate LA function and left ventricular
      function. METHODS: Sixty-four healthy subjects were studied. LA epsilon and SR
      were calculated with the reference point set at the P wave, which enabled the
      recognition of peak negative epsilon (epsilon(neg peak)), peak positive epsilon
      (epsilon(pos peak)), and the sum of those values, total LA epsilon
      (epsilon(tot)), corresponding to LA contractile, conduit, and reservoir function,
      respectively. Similarly, peak negative SR (LA SR(late neg peak)) during LA
      contraction, peak positive SR (LA SR(pos peak)) at the beginning of LV systole,
      and peak negative SR (LA SR(early neg peak)) at the beginning of LV diastole were
      identified. RESULTS: Global LA epsilon(pos peak), epsilon(neg peak), and
      epsilon(tot) were 23.2 +/- 6.7%, -14.6 +/- 3.5%, and 37.9 +/- 7.6%, respectively.
      Global LA SR(pos peak), SR(early neg peak) , and SR(late neg peak) were 2.0 +/-
      0.6 s(-1), -2.0 +/- 0.6 s(-1), and -2.3 +/- 0.5 s(-1), respectively. The above
      described variables derived from analysis of global LA epsilon and LA SR
      correlated significantly with Doppler echocardiographic indexes that evaluated
      the same phase of the cardiac cycle or the same component of the LA function,
      including indexes derived from mitral inflow, pulmonary vein velocities, tissue
      Doppler, and LA volumes. Global LA epsilon(pos peak), LA epsilon(tot), and LA
      SR(early neg peak) also correlated significantly with age or body mass index.
      Global LA SR(late neg peak) also correlated significantly with age. CONCLUSIONS:
      LA epsilon analysis is a new tool that can be used to evaluate LA function.
      Further studies are warranted to determine the utility of LA epsilon in disease
      states.

PMID- 20152700
TI  - Myocardial contractile function in the region of the left ventricular pacing lead
      predicts the response to cardiac resynchronization therapy assessed by two
      dimensional speckle tracking echocardiography.
AB  - BACKGROUND: The aim of this study was to test the impact of posterolateral
      myocardial systolic function on response to cardiac resynchronization therapy
      (CRT). METHODS: Forty patients were studied before and 4 +/- 2 months after CRT.
      Dyssynchrony was defined as anteroseptal wall-to-posterior wall delay (> or = 130
      ms) caused by speckle-tracking radial strain. The average longitudinal strain in
      4 posterior and lateral segments (epsilon-pl) in which the left ventricular
      pacing lead was positioned was calculated by automated functional imaging.
      Response to CRT was defined as a > or = 15% decrease in end-systolic volume.
      RESULTS: The negative value of epsilon-pl in responders was significantly higher
      than that in nonresponders at baseline (-7.8 +/- 6.9% vs -2.1 +/- 4.9%, P < .01).
      Combining dyssynchrony with epsilon-pl < -7.8% was more effective for predicting
      response to CRT than dyssynchrony parameters alone (92% vs 75%). CONCLUSION: The
      addition of posterolateral myocardial systolic function to the measurement of
      dyssynchrony appears to be of value for predicting response to CRT.

PMID- 20152701
TI  - Speckle tracking echocardiography for cardiac resynchronization therapy: has the
      right ultrasound technique finally been found?

PMID- 20152702
TI  - Myocardial contractile inefficiency and dyssynchrony in heart failure with
      preserved ejection fraction and narrow QRS complex.
AB  - BACKGROUND: Using speckle-tracking imaging (STI), the aims of this study were to
      assess dyssynchrony and quantify the myocardial energy wasted by contractility in
      delayed segments by determining the longitudinal strain delay index (LSDi) in
      patients with heart failure with preserved ejection fraction (HFpEF). METHOD:
      Thirty-eight patients with HFpEF and 33 matched controls were recruited. All
      subjects underwent clinical examinations, 12-lead electrocardiography, pulmonary
      function tests, echocardiography, and metabolic exercise tests. LSDi was
      determined, the magnitude of which is a measure of the amount of wasted energy.
      Global and segmental systolic and diastolic dyssynchrony was assessed by STI.
      RESULTS: LSDi was significantly higher in patients with HFpEF than controls (
      14.36 +/- 8.24% vs -10.73 +/- 5.62%, P < .05). Patients with HFpEF exhibited left
      ventricular (LV) systolic and diastolic dyssynchrony, with the LV anterior wall
      displaying the most delayed motion. CONCLUSION: Patients with HFpEF exhibited
      increased myocardial contractile inefficiency. They also exhibited LV systolic
      and diastolic dyssynchrony, with the LV anterior wall displaying the most delayed
      motion.

PMID- 20152703
TI  - Characteristics and outcomes of patients with abnormal stress echocardiograms and
      angiographically mild coronary artery disease (<50% stenoses) or normal coronary
      arteries.
AB  - BACKGROUND: Abnormal cardiac stress imaging findings are not always associated
      with angiographically significant coronary artery disease. The outcomes of
      patients with such false-positive findings have not been extensively examined.
      The aim of this retrospective study was to describe the characteristics and
      outcomes of patients with abnormal stress echocardiographic findings who had
      false-positive results compared with those who had true-positive results.
      METHODS: Of 1,477 consecutive patients (mean age, 66 +/- 12 years; 61% men) with
      abnormal stress echocardiographic findings who underwent coronary arteriography
      within 30 days, death from any cause was ascertained. RESULTS: At coronary
      arteriography, 997 patients (67.5%) had true-positive results, defined by the
      presence of angiographically significant coronary artery disease (> or = 50%
      stenoses), and 480 (32.5%) had false-positive results, defined by <50% stenoses
      or normal coronary arteries. Of the subgroup of patients with markedly abnormal
      stress echocardiographic findings (n = 605), 28% had <50% stenoses or normal
      coronary arteries. During an average follow-up period of 2.4 +/- 1.0 years, there
      were 140 deaths. The adjusted likelihood of subsequent death for patients with
      <50% stenoses compared to patients with > or = 50% stenoses after abnormal stress
      echocardiography was 1.05 (95% confidence interval, 0.86-1.31; P = .62).
      CONCLUSIONS: A sizable proportion of patients with abnormal stress
      echocardiographic results who are referred for coronary angiography have false
      positive findings. The outcomes of patients with false-positive results were
      similar to those of patients with true-positive results. This finding suggests
      that patients with false-positive results on stress echocardiography should still
      receive intensive risk factor management and careful clinical follow-up.

PMID- 20152704
TI  - The "myth" of the false positive stress echo.

PMID- 20152706
TI  - Advantages of individual patient data analysis in systematic reviews.

PMID- 20152707
TI  - Exenatide and weight loss.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone mainly
      released from the distal ileum, jejunum, and colon in response to food ingestion.
      It is categorized as an incretin due to its activation of GLP-1 receptors in
      pancreatic beta-cells leading to insulin exocytosis in a glucose-dependent
      manner. Exenatide (synthetic exendin-4) is a subcutaneously injected GLP-1
      receptor agonist that shares 50% homology with GLP-1. It is derived from lizard
      venom and stimulates the GLP-1 receptor for prolonged periods. The present review
      aims to enumerate exenatide-instigated weight loss, summarize the known
      mechanisms of exenatide-induced weight loss, and elaborate on its possible
      application in the pharmacotherapy of obesity. METHODS: A search through PubMed
      was performed using exenatide and weight loss as search terms. A second search
      was performed using exenatide and mechanisms or actions as search terms. RESULTS:
      In addition to exenatide's action to increase insulin secretion in individuals
      with elevated levels of plasma glucose, clinical trials have reported consistent
      weight loss associated with exenatide treatment. Studies have found evidence that
      exenatide decreases energy intake and increases energy expenditure, but findings
      on which predominates to cause weight loss are often inconsistent and
      controversial. CONCLUSION: Further research on the effects of exenatide treatment
      on energy intake and expenditure are recommended to better understand the
      mechanisms through which exenatide causes weight loss.

PMID- 20152708
TI  - Should we routinely offer a second admission for radioiodine to patients with
      high-risk differentiated thyroid cancer?
AB  - AIMS: To assess whether an elective second admission for radioiodine is useful
      for patients with high-risk differentiated thyroid cancer (DTC). MATERIALS AND
      METHODS: A retrospective analysis was carried out on 47 high-risk DTC patients
      treated with a second admission for radioiodine at our centre during the 2007
      2008 period. RESULTS: In 21 patients (45%), the surgeon described an incomplete
      resection. Twenty-six (55%) had surgical macroscopic complete resection, but
      cancer cells at the margin of excision histologically. Overall, at the second
      admission for radioiodine, 27 patients (57%) had a normal post-treatment scan and
      undetectable thyroid-stimulating hormone (TSH) stimulated thyroglobulin. Twenty
      patients (43%) had raised stimulated thyroglobulin at second admission for
      radioiodine, of whom only six (13%) had abnormal uptake (>0.1%) on the post
      treatment scan. CONCLUSIONS: A second admission for radioiodine could have been
      avoided in most patients. Instead, information from stimulated thyroglobulin and
      a diagnostic radioiodine scan would have been sufficient to guide further
      management. This study also provides interesting outcome data on incompletely
      resected DTC.

PMID- 20152709
TI  - 111In- or 99mTc-labeled recombinant VEGF bioconjugates: in vitro evaluation of
      their cytotoxicity on porcine aortic endothelial cells overexpressing Flt-1
      receptors.
AB  - INTRODUCTION: The aims of this study were to (a) synthesize and characterize a
      novel vascular endothelial growth factor (VEGF-2K) recombinant protein expressed
      in Pichia pastoris and (b) compare its cytotoxicity when labeled with the Auger
      electron emitter (111)In or (99m)Tc, both of which are in the nanometer
      micrometer range, toward porcine aortic endothelial (PAE) cells transfected with
      the flt-1 gene to overexpress Flt-1 receptors (PAE-Flt-1). METHODS: The gene for
      the VEGF(165) isoform was fused to a sequence encoding an extended flexible
      peptide (KGGGGSK) with two accessible lysines for preferential derivatization
      with diethylenetriaminepentaacetic acid (DTPA) for complexing (111)In and a
      sequence for a His(6) affinity tag that bound the [(99m)Tc(CO)(3)(H(2)O)(3)](+)
      tricarbonyl complex. P. pastoris strain KM71H was transfected with the
      recombinant gene, the VEGF-2K protein expressed with methanol induction, and then
      purified by metal-affinity chromatography. VEGF-2K was modified with 13-mer
      peptides [CGYGPKKKRKVGG] containing the nuclear localization sequence (NLS) of SV
      40 large T-antigen (underlined) to promote nuclear uptake following its receptor
      mediated internalization. RESULTS: (99m)Tc-DTPA-VEGF-2K bound strongly and
      preferentially to PAE-Flt-1 cells compared with non-transfected PAE cells, but
      NLS modification diminished the ratio of PAE-Flt-1 to PAE binding to 2.3-fold.
      Nuclear accumulation of (99m)Tc-labeled DTPA-VEGF-2K was not enhanced by NLS
      modification but was enhanced by 1.5-fold for (111)In-DTPA-VEGF-2K-NLS. However,
      confocal microscopy revealed intranuclear distribution of DTPA-VEGF-2K-NLS,
      whereas DTPA-VEGF-2K distribution was mainly perinuclear. (111)In-DTPA-VEGF-2K
      NLS was the most cytotoxic to PAE-Flt-1 cells, reducing their clonogenic survival
      by 4-fold. (111)In-DTPA-VEGF-2K, (99m)Tc-DTPA-VEGF-2K or (99m)Tc-DTPA-VEGF-2K-NLS
      had less effect on the clonogenic survival of PAE-Flt-1 or PAE cells. The strong
      cytotoxicity of (111)In-DTPA-VEGF-2K-NLS toward PAE-Flt-1 cells was associated
      with a 27-fold increase in nuclear foci of immunofluorescence for phosphorylated
      histone-2AX corresponding to sites of unrepaired DNA double-strand breaks. Monte
      Carlo modeling revealed that radionuclide decay in the nucleus would provide a 5
      fold higher radiation absorbed dose for (111)In than for (99m)Tc, explaining
      their differential cytotoxicity, and intranuclear localization would amplify the
      radiation dose delivered by (111)In by 3-fold, explaining the greater potency of
      (111)In-DTPA-VEGF-2K-NLS compared with (111)In-DTPA-VEGF-2K. CONCLUSIONS: We
      conclude that targeted Auger electron radiotherapy aimed at Flt-1 receptors is a
      promising strategy that should be explored further for treatment of tumors in
      which this angiogenic pathway is up-regulated. (111)In is a more cytotoxic
      radionuclide than (99m)Tc, unless DNA delivery can be achieved, due to the short
      range of the electrons emitted.

PMID- 20152710
TI  - Preliminary studies of 99mTc-BnAO and its analogues: synthesis, radiolabeling and
      in vitro cell uptake.
AB  - INTRODUCTION: (99m)Tc-BnAO is one of the nonnitroimidazole hypoxia markers with
      the highest citation and could be potentially useful in both oncology and other
      clinical applications. However, it appears inferior in vitro due to lower
      absolute accumulation and smaller anoxic/normoxic uptake ratio. It is possible
      that the analogues of (99m)Tc-BnAO have higher hypoxia selectivity after the
      ligand of (99m)Tc-BnAO is modified. METHODS: 2,2'-(1,4-Diaminobutane)bis(2-methyl
      3-butanone) dioxime (BnAO or HL91) and three novel analogues were synthesized and
      radiolabeled with technetium-99m. The cellular uptake of the radiolabeled
      complexes was determined in murine sarcoma S180 cell lines under anoxic and
      normoxic conditions. RESULTS: (99m)Tc-BnAO and its three novel analogues
      continuously accumulated in anoxic cells but not in normoxic ones, while the
      analogues showed earlier hypoxia selectivity and greater anoxic/normoxic
      differential. CONCLUSIONS: The analogues are superior to (99m)Tc-BnAO in terms of
      in vitro hypoxia selectivity and are viable candidates for further development as
      new nonnitroimidazole hypoxia markers in the future.

PMID- 20152711
TI  - Hypoxia-induced redox alterations and their correlation with 99mTc-MIBI and 99mTc
      HL-91 uptake in colon cancer cells.
AB  - Colorectal cancer is one of the most common malignancies in the Western world and
      is an example of a solid tumour in which hypoxia is a common feature and develops
      because of the inability of the vascular system to supply adequate amounts of
      oxygen to growing tumours. Hypoxia effects on tumour cell biology can be detected
      and characterized using different methods. The use of imaging with gamma-emitting
      radionuclides to detect hypoxic tissue was first suggested by Chapman in 1979 [N
      Engl J Med 301 (1979) 1429-1432]. (99m)Tc-4,9-diaza-3,3,10,10-tetramethyldodecan
      2,11-dione dioxime, also known as (99m)Tc-HL-91, has been among the most studied
      hypoxia markers. The objective of this study was to correlate the uptake of
      (99m)Tc-HL-91 and (99m)Tc-MIBI in colon cancer cells under normoxic and hypoxic
      conditions and to compare this information with some parameters such as oxidative
      stress and mitochondrial dysfunction of the cells analyzed by flow cytometry. Our
      results show that the in vitro (99m)Tc-HL-91 uptake is higher in hypoxic
      conditions, which is confirmed by the decreased uptake of (99m)Tc-MIBI. Flow
      cytometry results demonstrate that hypoxic conditions used are not enough to
      induce cellular death, but are responsible for the alterations in the
      intracellular redox environment, namely, increase of ROS production, proteic
      pimonidazol-derived adduct formation and alteration in the mitochondrial membrane
      permeability. Therefore, these results confirm that (99m)Tc-HL-91 is a
      radiopharmaceutical with favourable characteristics for detecting hypoxia.

PMID- 20152712
TI  - An improved radiosynthesis of [18F]AV-133: a PET imaging agent for vesicular
      monoamine transporter 2.
AB  - INTRODUCTION: Recently, a PET tracer, 9-[(18)F]fluoropropyl-(+)
      dihydrotetrabenazine ([(18)F]AV-133), targeting vesicular monoamine transporter 2
      (VMAT2) in the central nervous system has been reported. It is currently under
      Phase II clinical trials to establish its usefulness in the diagnosis of
      neurodegenerative diseases including dementia with Lewy bodies and Parkinson's
      disease. The radiolabeling of [(18)F]AV-133, nucleophilic fluorination reaction
      and potential effects of pseudo-carrier were evaluated by in vivo
      biodistribution. METHODS: The preparation of [(18)F]AV-133 was evaluated under
      different conditions, specifically by employing different precursors (-OTs or -Br
      as the leaving group at the 9-propoxy position), reagents (K222/K(2)CO(3) vs.
      tributylammonium bicarbonate) and solvents (acetonitrile vs. DMSO), reaction
      temperature and reaction time. With optimized conditions from these experiments,
      radiosynthesis and purification with solid-phase extraction (SPE) of [(18)F]AV
      133 were performed by an automated nucleophilic [(18)F]fluorination module. In
      vivo biodistribution in mice on [(18)F]AV-133 purified by either HPLC (no-carrier
      added) or the SPE method (containing a pseudo-carrier) was performed and the
      results compared. RESULTS: Under a mild fluorination condition (heating at 115
      degrees C for 5 min in dimethyl sulfoxide), [(18)F]AV-133 was obtained in a high
      yield using either -OTs or -Br as the leaving group. However, the -OTs precursor
      gave better radiochemical yields (>70%, thin layer chromatography analysis)
      compared to those of the -Br precursor. The optimized reaction conditions were
      successfully implemented to an automated nucleophilic fluorination module.
      Labeling and purification of [(18)F]AV133 were readily achieved via this
      automatic module in good radiochemical yield of 21-41% (n=10) in 40 min. The
      radiochemical purity was larger than 95%. Biodistribution of SPE-purified product
      (containing a pseudo-carrier) in mice showed a high striatum/cerebellum ratio
      (4.18+/-0.51), which was comparable to that of HPLC-purified [(18)F]AV-133
      (4.51+/-0.10). CONCLUSIONS: The formation of [(18)F]AV-133 was evaluated under
      different labeling conditions. These improved labeling conditions and SPE
      purification were successfully implemented into an automated synthesis module.
      This offers a short preparation time (about 40 min), simplicity in operation and
      ready applicability for routine clinical operation.

PMID- 20152713
TI  - A 1-methyl-4-piperidinyl cytectrene carboxylate labeled by the technetium 99m, a
      radiotracer for rat brain acetylcholinesterase activity.
AB  - Alzheimer's disease (AD) is a degenerative neurological disorder that causes
      progressive and irreversible loss of connections between brain cells and loss of
      mental functions. Clinical and postmortem studies show that the biochemical
      changes in brains of AD patients include decrease in acetylcholinesterase (AChE)
      activity. Our aim was to study AChE activity using piperidinyl ester labelled
      with technetium-99m. In vivo and in vitro studies demonstrated that labelled
      piperidinyl ester was a substrate for AChE. The hydrolytic rate of this substrate
      was measured and the specificity was evaluated using the inhibitor BW284c51. The
      rhenium analogues of the technetium-labelled substrate were used to determine the
      affinity constant (K(m)) and the maximum reaction velocity (V(max)) because of
      the high specific activity of technetium. The high hydrolytic rate and high
      specificity of the substrate for AChE make it suitable as an in vivo radiotracer
      for studying AChE activity in the brain.

PMID- 20152714
TI  - Formulation of 68Ga BAPEN kit for myocardial positron emission tomography imaging
      and biodistribution study.
AB  - INTRODUCTION: Tris(4,6-dimethoxysalicylaldimine)-N,N'-bis(3-aminopropyl)-N,N'
      ethylenediamine (BAPEN), a tris(salicylaldimine) derivative, is a heart positron
      emission tomography (PET) agent when labeled with (68)Ga. However, its labeling
      requires complicated and time-consuming procedures. In this study, the authors
      formulated a new BAPEN kit for convenient (68)Ga labeling. METHODS: BAPEN (0.25
      mg) kits were prepared by dispensing its solution in 1 M sodium acetate buffer
      (pH 5.5) into sterile vials and lyophilization. The prepared kits were labeled
      with generator-eluted (68)Ga in 0.1 N HCl. Stability in human serum was tested.
      Expiration date was determined by accelerated testing according to US Food and
      Drug Administration guidelines. A Biodistribution study was performed in normal
      mice after injection via tail vein. RESULTS: The prepared kits achieved
      radiolabeling efficiencies in excess of 95% and showed a shelf-life of 98 days at
      25 degrees C and 64.3 months at 4 degrees C. (68)Ga-BAPEN was found to be stable
      in human serum at 37 degrees C for at least 1 h. Furthermore, a biodistribution
      study revealed high heart uptake (10.8% ID/g, 1 h). CONCLUSIONS: The authors
      developed a BAPEN kit for convenient labeling with (68)Ga. The (68)Ga-BAPEN
      showed high stability and excellent biodistribution results in normal mice, which
      is required for myocardial PET imaging.

PMID- 20152715
TI  - Tumor uptake of 68Ga-DOTA-Tyr3-octreotate: animal PET studies of tumor flow and
      acute somatostatin receptor modulation in the CA20948 rat model.
AB  - INTRODUCTION: Factors determining the in vivo uptake of radiolabeled somatostatin
      analogs by neuroendocrine tumors are poorly known. The aim is to evaluate in vivo
      tumor perfusion and regulation of somatostatin receptors (sstr) following acute
      exposure to octreotide, in an animal model of neuroendocrine tumor. METHODS:
      H(2)(15)O flow studies were performed in 8 CA20948 tumor-bearing rats and another
      36 rats underwent three [(68)Ga]-DOTA-Tyr(3)-octreotate imaging sessions at 24-h
      intervals. After baseline (Day 0) imaging, scanning was repeated on Day 1 after
      octreotide injection (175 microg/kg), with a variable delay: no injection
      (controls, n=7), coinjection (n=6), and octreotide injection 20 min (n=7), 2 h
      (n=8) and 4 h (n=8) before imaging. Repeat images without octreotide was
      performed at Day 2 followed by sacrifice and tumor counting. RESULTS: H(2)(15)O
      studies failed to measure quantitative tumor perfusion in this model. On Day 1,
      ratio of tumor uptake to Day 0 was 1.2+/-0.3 in controls; 0.6+/-0.2 in the
      coinjection group; 0.9+/-0.2, 1.1+/-0.1 and 1.2+/-0.2 in the other groups,
      respectively. Uptake in the coinjection group showed a statistically significant
      reduction of tumor uptake (P<.0001). All groups showed increased uptake on Day 2,
      without statistical differences between groups. In vivo tumor counts showed good
      correlation with ex vivo countings (R(2)=0.946). CONCLUSION: Acute exposure to
      unlabeled octreotide in this neuroendocrine tumor model results in a rapid
      recycling or resynthesis of sstr. Positron emission tomography (PET) allowed to
      reliably assess quantitative uptake of [(68)Ga]-DOTA-Tyr(3)-octreotate over time
      in the same animal, but failed in this model to measure tumor perfusion.

PMID- 20152716
TI  - Preparation and in vivo evaluation of radioiodinated closo-decaborate(2-)
      derivatives to identify structural components that provide low retention in
      tissues.
AB  - INTRODUCTION: In vivo deastatination of (211)At-labeled biomolecules can severely
      limit their use in endoradiotherapy. Our studies have shown that the use of closo
      decaborate(2-) moiety for (211)At-labeling of biomolecules provides high in vivo
      stability towards deastatination. However, data from those studies have also been
      suggestive that some astatinated closo-decaborate(2-) catabolites may be retained
      in tissues. In this study, we investigated the in vivo distributions of several
      structurally simple closo-decaborate(2-) derivatives to gain information on the
      effects of functional groups if catabolites are released into the blood system
      from the carrier biomolecule. METHODS: Thirteen closo-decaborate(2-) derivatives
      were synthesized and radioiodinated for evaluation. Tissue concentrations of the
      radioiodinated compounds were obtained in groups of five mice at 1 and 4 h
      postinjection (pi). Dual-label ((125)I and (131)I) experiments permitted
      evaluation of two compounds in each set of mice. RESULTS: All of the target
      compounds were readily synthesized. Radioiodination reactions were conducted with
      chloramine-T and Na[(125/131)I]I in water to give high yields (75-96%) of the
      desired compounds. Biodistribution data at 1 and 4 h pi (representing catabolites
      released into the blood system) showed small differences in tissue concentrations
      for some compounds, but large differences for others. The results indicate that
      formal (overall) charge on the compounds could not be used as a predictor of
      tissue localization or retention. However, derivatives containing carboxylate
      groups generally had lower tissue concentrations. Acid cleavable hydrazone
      functionalities appeared to be the best candidates for further study.
      CONCLUSIONS: Further studies incorporating hydrazone functionalities into pendant
      groups for biomolecule radiohalogenation are warranted.

PMID- 20152717
TI  - C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti
      c-kit monoclonal antibody in a mouse tumor model.
AB  - INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common
      mesenchymal tumor arising from the gastrointestinal tract and highly expresses
      mutated c-kit. We aimed to develop a specific and sensitive method for detecting
      GISTs using radiolabeled anti-c-kit monoclonal antibody. METHODS: A mutated c-kit
      expressing cell clone was established by transfecting an expressing vector of
      mutated c-kit gene into HEK293 human embryonic kidney cells. The tumors were
      developed by inoculating c-kit-expressing cells into nude mice. (125)I- and
      (111)In-labeled anti-c-kit antibodies (12A8 and 41A11) were evaluated in vitro by
      cell binding, competitive inhibition and cellular internalization assays, and in
      vivo by biodistribution and imaging studies in tumor-bearing mice. RESULTS: Both
      (125)I- and (111)In-labeled antibodies showed specific binding with c-kit
      expressing cells with high affinity (dissociation constants = 2.2-7.1x10(9) M(
      1)). Internalization assay showed that (125)I-labeled antibodies were rapidly
      internalized and dehalogenated, with the release of (125)I from the cells,
      resulting in reduction of cell-associated radioactivity with time. In contrast,
      (111)In-labeled antibody was internalized but did not result in the reduced
      radioactivity associated with tumor cells. Reflecting this phenomenon, the in
      vivo tumor uptake of (125)I-labeled antibody was low on Day 1, further decreasing
      with time, while tumor uptake of (111)In-labeled antibody was high on Day 1,
      further increasing with time. The xenografted tumor was clearly visualized by
      scintigraphy after injection of (111)In-labeled antibody. CONCLUSION: The anti-c
      kit monoclonal antibody labeled with a metal radionuclide would be promising for
      c-kit-targeted imaging of GISTs.

PMID- 20152718
TI  - Stimulation of 125I-3-iodo-alpha-methyl-L-tyrosine uptake in Chinese hamster
      ovary (CHO-K1) cells by tyrosine esters.
AB  - INTRODUCTION: Transport of the amino acid analog (123)I-3-iodo-alpha-methyl-L
      tyrosine, which is used in clinical SPECT imaging, occurs mainly via L-type amino
      acid transporter type 1 (LAT1; an amino acid exchanger). As LAT1 is highly
      expressed in actively proliferating tumors, we made a preliminary investigation
      of the effects of amino acid esters on enhancement of (125)I-3-iodo-alpha-methyl
      L-tyrosine (IMT) uptake via LAT1 in Chinese hamster ovary (CHO-K1) cells.
      METHODS: Because the sequence of the CHO-K1 LAT1 gene is not available, we
      confirmed LAT1 expression through IMT (18.5 kBq) uptake mechanisms using specific
      inhibitors. L-Gly, L-Ser, L-Leu, L-Phe, L-Met, L-Tyr, D-Tyr, L-Val and L-Lys
      ethyl/methyl esters were tested in combination with IMT. Time-course studies over
      a 3-h period were conducted, and the concentration dependence of L-Tyr ethyl and
      methyl esters (0.001 to 10 mM) in combination with IMT was also examined. For a
      proof of de-esterification of L- and D-Tyr ethyl and methyl esters in the cells
      (by enzymatic attack or other cause), the concentration of L- and D-Tyr was
      analyzed by high-performance liquid chromatography of the esters in phosphate
      buffer (pH 7.4) and cell homogenates at 37 degrees C or under ice-cold
      conditions. RESULTS: Inhibition tests suggested that LAT1 is involved in IMT
      uptake by CHO-K1 cells. Co-administration of 1 mM of l-Tyr ethyl or methyl ester
      with IMT produced the greatest enhancement. The de-esterification reaction was
      stereo selective and temperature dependent in the homogenate. De-esterification
      kinetics were very fast in the homogenate and very slow in the phosphate buffer.
      CONCLUSIONS: The L-Tyr ethyl or methyl esters were the most effective enhancers
      of IMT uptake into CHO-K1 cells and acted by trans-stimulation of the amino acid
      exchange function of LAT1. This result suggests that de-esterification in the
      cells may be caused by enzymatic attack. We will use IMT and L-Tyr ethyl or
      methyl esters to examine LAT1 function in tumor cells or tissues in vivo.

PMID- 20152719
TI  - Uptake of 3-[125I]iodo-alpha-methyl-L-tyrosine into colon cancer DLD-1 cells:
      characterization and inhibitory effect of natural amino acids and amino acid-like
      drugs.
AB  - INTRODUCTION: We examined 3-[(123)I]iodo-alpha-methyl-L-tyrosine ([(123)I]IMT)
      uptake and inhibition by amino acids and amino acid-like drugs in the human DLD-1
      colon cancer cell line, to discuss correlation between the inhibition effect and
      structure. METHODS: Expression of relevant neutral amino acid transporters was
      examined by real-time PCR with DLD-1 cells. The time course of [(125)I]IMT
      uptake, contributions of transport systems, concentration dependence and
      inhibition effects by amino acids and amino acid-like drugs (1 mM) on [(125)I]IMT
      uptake were examined. RESULTS: Expression of system L (4F2hc, LAT1 and LAT2),
      system A (ATA1, ATA2) and system ASC (ASCT1) was strongly detected; system L
      (LAT3, LAT4) and MCT8 were weakly detected; and B(0)AT was not detected.
      [(125)I]IMT uptake in DLD-1 cells involved Na(+)-independent system L primarily
      and Na(+)-dependent system(s). Uptake of [(125)I]IMT in Na(+)-free buffer
      followed Michaelis-Menten kinetics, with a K(m) of 78 microM and V(max) of 333
      pmol/10(6) cells per minute. Neutral D- and L-amino acids with branched or
      aromatic large side chains inhibited [(125)I]IMT uptake. Tyrosine analogues,
      tryptophan analogues, L-phenylalanine and p-halogeno-L-phenylalanines, and gamma
      amino acids [including 3,4-dihydroxy-L-phenylalanine (L-DOPA), DL-threo-beta-(3,4
      dihydroxyphenyl)serine (DOPS), 4-[bis(2-chloroethyl)amino]-L-phenylalanine and 1
      (aminomethyl)-cyclohexaneacetic acid] strongly inhibited [(125)I]IMT uptake, but
      L-tyrosine methyl ester and R(+)/S(-)-baclofen weakly inhibited uptake. The
      substrates of system ASC and A did not inhibit [(125)I]IMT uptake except L-serine
      and D/L-cysteine. CONCLUSIONS: [(125)I]IMT uptake in DLD-1 cells involves mostly
      LAT1 and its substrates' (including amino acid-like drugs derived from tyrosine,
      tryptophan and phenylalanine) affinity to transport via LAT1. Whether transport
      of gamma amino acid analogues is involved in LAT1 depends on the structure of the
      group corresponding to the amino acid residue. Beta-hydroxylation may confer
      reduction of transport affinity of tyrosine analogues via LAT1.

PMID- 20152720
TI  - High-resolution imaging of brain 5-HT 1B receptors in the rhesus monkey using
      [11C]P943.
AB  - The serotonin 5-HT(1B) receptors regulate the release of serotonin and are
      involved in various disease states, including depression and schizophrenia. The
      goal of the study was to evaluate a high affinity and high selectivity
      antagonist, [(11)C]P943, as a positron emission tomography (PET) tracer for
      imaging the 5-HT(1B) receptor. [(11)C]P943 was synthesized via N-methylation of
      the precursor with [(11)C]methyl iodide or [(11)C]methyl triflate using automated
      modules. The average radiochemical yield was approx. 10% with radiochemical
      purity of >99% and specific activity of 8.8+/-3.6 mCi/nmol at the end-of
      synthesis (n=37). PET imaging was performed in non-human primates with a high
      resolution research tomograph scanner with a bolus/infusion paradigm. Binding
      potential (BP(ND)) was calculated using the equilibrium ratios of regions to
      cerebellum. The tracer uptake was highest in the globus pallidus and occipital
      cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum,
      which is consistent with the known brain distribution of 5-HT(1B) receptors.
      Infusion of tracer at different specific activities (by adding various amount of
      unlabeled P943) reduced BP(ND) values in a dose-dependent manner, demonstrating
      the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg
      iv), a selective 5-HT(1B)/5-HT(1D) antagonist, resulted in reduction of BP(ND)
      values by 42-95% across regions; for an example, in occipital region from 0.71 to
      0.03, indicating a complete blockade. These results demonstrate the saturability
      and specificity of [(11)C]P943 for 5-HT(1B) receptors, suggesting its suitability
      as a PET radiotracer for in vivo evaluations of the 5-HT(1B) receptor system in
      humans.

PMID- 20152721
TI  - Multispecies animal investigation on biodistribution, pharmacokinetics and
      toxicity of 177Lu-EDTMP, a potential bone pain palliation agent.
AB  - INTRODUCTION: Radionuclide therapy (RNT) is an effective method for bone pain
      palliation in patients suffering from bone metastasis. Due to the long half-life,
      easy production and relatively low beta- energy, (177)Lu [T(1/2)=6.73 days,
      E(beta max)=497 keV, E(gamma)=113 keV (6.4%), 208 keV (11%)]-based
      radiopharmaceuticals offer logistical advantage for wider use. This paper reports
      the results of a multispecies biodistribution and toxicity studies of (177)Lu
      EDTMP to collect preclinical data for starting human clinical trials. METHODS:
      (177)Lu-EDTMP with radiochemical purity greater than 99% was formulated by using
      a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH).
      Biodistribution studies were conducted in mice and rabbits. Small animal imaging
      was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital
      autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels
      of activity (9.25 through 37 MBq/kg body weight) of (177)Lu-EDTMP were injected
      in four groups of three dogs each to study the toxicological effects. RESULTS:
      (177)Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41%
      of the injected activity in bone with terminal elimination half-life of 2130 and
      1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h.
      Excretion of the radiopharmaceutical was through the urinary system. Imaging
      studies showed that all species (mouse, rat, rabbit and dog) take up the compound
      in regions of remodeling bone, while kidney retention is not visible after 1 day
      postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight)
      led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi
      with no toxicity. CONCLUSION: The protracted effective half-life of (177)Lu-EDTMP
      in bone supports that modifying the EDTMP molecule by introducing (177)Lu does
      not alter its biological behaviour as a specific bone-seeking tracer. Species
      specific pharmacokinetic behavior differences were observed. Toxicity studies in
      dogs did not show any biological adverse effects. The studies demonstrate that
      (177)Lu-EDTMP is a promising radiopharmaceutical that can be further evaluated
      for establishing as a radiopharmaceutical for human use.

PMID- 20152722
TI  - Three-region MRI-based whole-body attenuation correction for automated PET
      reconstruction.
AB  - INTRODUCTION: In this study we proposed and developed a simple attenuation
      mapping approach based on magnetic resonance imaging (MRI) for the purpose of
      reconstructing positron emission tomography (PET) images in PET/MRI imaging
      devices. METHODS: After experimental development, an in vivo calibration was
      performed by whole-body scanning of five beagles on both a PET/CT and an MRI. The
      attenuation was determined by using an automated segmentation algorithm to
      segment regions of background, lung, soft tissue and bone, and assigning them
      values of 0.002, 0.030, 0.098 and 0.130 cm(-1), respectively. RESULTS: The CT
      attenuated and MRI-attenuated PET images had average standardized uptake values
      (SUVs) that differed by 1-6% for most regions of interest (ROIs). Also, mean
      relative differences (MRDs) between the images were between 5% and 9% for most
      regions. The only exception is bone, where the three-region MRI-attenuated PET
      images had an SUV 10% less on average than the CT-attenuation images, and the MRD
      averaged 14%. Also, additional segmentation of the bone in the four-region MRI
      attenuated PET images reduced the SUV difference to 3% and the MRD to 6%.
      CONCLUSION: Therefore, despite the improvements in the four-region segmentation,
      the three-region segmentation, without delineation of osseous tissues, produces
      high-quality images that are sufficient for most expected clinical and research
      purposes.

PMID- 20152723
TI  - Magnetic fields and the brain at high field strengths what do we know?

PMID- 20152725
TI  - Volumetric analysis of pulmonary CTA for the assessment of right ventricular
      dysfunction in patients with acute pulmonary embolism.
AB  - RATIONALE AND OBJECTIVES: To retrospectively determine the value of a volumetric
      ventricle analysis for the assessment of right ventricular dysfunction in
      patients with suspected pulmonary embolism (PE) by using image data from non
      electrocardiographically (ECG)-gated multidetector computed tomography
      angiography (CTA). MATERIALS AND METHODS: Hypothesizing that the presence of PE
      and the embolus location correlated with right ventricular dysfunction, we
      retrospectively analyzed 100 non-ECG-gated pulmonary CTA datasets of patients
      with central, peripheral, and without PE. Right ventricle/left ventricle (RV/LV)
      diameter ratio measured in transverse sections (RV/LV(trans)), four-chamber view
      (RV/LV(4ch)), and RV/LV volume ratio (RV/LV(vol)) were assessed on CT images. The
      results were correlated with the embolus location, the 30-day mortality rate, and
      the necessity of intensive care treatment. RESULTS: All CT parameters showed
      statistically significant differences between all patients groups depended on
      embolus location. The receiver operating characteristic analysis RV/LV(vol)
      showed the strongest discriminatory power to differ between patients with central
      and without PE and between patients with central and peripheral PE (central PE
      vs. no PE: RV/LV(vol) = 0.932, RV/LV(trans) = 0.880, and RV/LV(4ch) = 0.811,
      central PE vs. peripheral PE: RV/LV(vol) = 0.950, RV/LV(trans) = 0.849, and
      RV/LV(4ch) = 0.881), indicating a correlation with embolus location predisposing
      for RVD. For the identification of high-risk patients with PE all three CT
      parameters showed statistically significant values (P < .0001), whereas in the
      receiver operating characteristic analysis, RV/LV(vol) had the strongest
      discriminatory power (RV/LV(vol) = 0.819, RV/LV(trans) = 0.799, and RV/LV(4ch) =
      0.758). CONCLUSION: Ventricle volumetry of non-ECG-gated CTA allows the
      assessment of right ventricular dysfunction in patients with acute PE. Compared
      to unidimensional measurements, a volumetric analysis seems to be slightly
      superior to identify high-risk patients with adverse clinical outcome. However,
      the method is more time consuming and requires dedicated software tools compared
      to unidimensional parameters, which is disadvantageous in an emergency setting.

PMID- 20152724
TI  - MRI-coupled fluorescence tomography quantifies EGFR activity in brain tumors.
AB  - RATIONALE AND OBJECTIVES: This report demonstrates the diagnostic potential of
      magnetic resonance imaging (MRI)-coupled fluorescence molecular tomography (FMT)
      to determine epidermal growth factor receptor (EGFR) status in brain cancer.
      MATERIALS AND METHODS: Two orthotopic glioma xenograft models were used in this
      study: one represented high EGFR expression and the other low expression. Nude
      mice were inoculated with cells from either one of the tumor lines or were used
      in a sham surgery control group. Animals were imaged using a unique MRI-FMT
      scanner 48 hours after intravenous injection of a near-infrared fluorophore bound
      to epidermal growth factor (EGF) ligand. Coronal images of fluorescence activity
      of the injected dye in the mouse brain were recovered using the MRI images as
      anatomical templates. RESULTS: In vivo images of fluorescence activity showed
      significant differences between animal populations, an observation confirmed by
      receiver operating characteristic analysis that revealed 100% sensitivity and
      specificity between animal groups implanted with EGFR((+)) and EGFR((-)) tumor
      lines. Similar performance was observed between EGFR((+)) and sham surgery
      control animals. CONCLUSIONS: This preclinical study suggests that MRI-FMT with
      fluorescent EGF provides excellent discrimination between tumors based on EGFR
      status. Reliable quantification of receptor status using minimally invasive
      techniques would be an important innovation for investigating new and existing
      cancer treatments that target these cellular mechanisms in research animals, and
      may be applied to identify receptor amplification in human brain cancer patients.
      This study represents the first systematic multianimal validation of receptor
      specific imaging using MRI-guided fluorescence tomography.

PMID- 20152726
TI  - Computer-aided diagnosis of lung nodules on CT scans: ROC study of its effect on
      radiologists' performance.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the effect of
      computer-aided diagnosis (CAD) on radiologists' estimates of the likelihood of
      malignancy of lung nodules on computed tomographic (CT) imaging. METHODS AND
      MATERIALS: A total of 256 lung nodules (124 malignant, 132 benign) were
      retrospectively collected from the thoracic CT scans of 152 patients. An
      automated CAD system was developed to characterize and provide malignancy ratings
      for lung nodules on CT volumetric images. An observer study was conducted using
      receiver-operating characteristic analysis to evaluate the effect of CAD on
      radiologists' characterization of lung nodules. Six fellowship-trained thoracic
      radiologists served as readers. The readers rated the likelihood of malignancy on
      a scale of 0% to 100% and recommended appropriate action first without CAD and
      then with CAD. The observer ratings were analyzed using the Dorfman-Berbaum-Metz
      multireader, multicase method. RESULTS: The CAD system achieved a test area under
      the receiver-operating characteristic curve (A(z)) of 0.857 +/- 0.023 using the
      perimeter, two nodule radii measures, two texture features, and two gradient
      field features. All six radiologists obtained improved performance with CAD. The
      average A(z) of the radiologists improved significantly (P < .01) from 0.833
      (range, 0.817-0.847) to 0.853 (range, 0.834-0.887). CONCLUSION: CAD has the
      potential to increase radiologists' accuracy in assessing the likelihood of
      malignancy of lung nodules on CT imaging.

PMID- 20152727
TI  - Comparison of conventional abdominal CT with MR-enterography in patients with
      active Crohn's disease and acute abdominal pain.
AB  - RATIONALE AND OBJECTIVES: Patients with known Crohn's disease (CD) and an acute
      onset of severe abdominal pain attending an emergency room frequently undergo
      contrast-enhanced emergency computed tomography (CT) for complication assessment.
      To assess small bowel changes, an additional dedicated imaging procedure such as
      magnetic resonance enterography (MRE) is regularly performed. Therefore, these
      patients undergo two imaging procedures, although the clinical and diagnostic
      value of such an approach is not known. In a retrospective study, we compared the
      diagnostic value of a conventional abdominal CT with a dedicated small bowel MRE
      to assess bowel wall changes as well as typical complications in patients with
      advanced CD. MATERIALS AND METHODS: We retrospectively evaluated 53 patients with
      CD having a conventional abdominal multidetector-CT (MD-CT) and MRE within 2
      days. Image quality and bowel inflammation was analyzed for each bowel segment.
      Lymph nodes, abscesses, and fistulas were evaluated. RESULTS: For small bowel and
      colon assessment, there was no significant difference for image quality between
      CT and MRE. Inflammation diagnosis was not significantly different between CT
      (69.4%) and MRE (71.4%). Colonic inflammation was diagnosed in 30.2% based on CT
      and 14.3% based on MRE. The difference for the detection of lymph nodes was
      significant (CT 49; MRE 27), whereas the differences between fistula (CT 25, MRE
      27) or abscesses (CT and MRE 32) detection were not significant. CONCLUSIONS: In
      patients with known advanced CD with acute abdominal pain conventional abdominal
      MD-CT, which is frequently performed as an emergency imaging procedure, is
      sufficient for bowel wall assessment. Based on our data, additional dedicated
      small bowel imaging such as MRE seems not to be necessary.

PMID- 20152729
TI  - Thresholds to lung density measures.

PMID- 20152730
TI  - Flexner report on medical education.

PMID- 20152732
TI  - Antifungal management.

PMID- 20152733
TI  - Time for diabetes surgery is it coming?

PMID- 20152734
TI  - What can bariatric surgery teach us about the pathophysiology of type 2 diabetes?
AB  - Bariatric surgery is indicated in cases of severe obesity. However, malabsorption
      based techniques (gastric bypass and biliopancreatic diversion, both of which
      exclude the duodenum and jejunum from the alimentary circuit), but not
      restrictive techniques, can abolish type 2 diabetes within days of surgery, even
      before any significant weight loss has occurred. This means that calorie
      restriction alone cannot entirely account for this effect. In Goto-Kakizaki rats,
      a type 2 diabetes model, glycaemic equilibrium is improved by surgical exclusion
      of the proximal intestine, but deteriorates again when the proximal intestine is
      reconnected to the circuit in the same animals. This effect is independent of
      weight, suggesting that the intestine is itself involved in the immediate
      regulation of carbohydrate homoeostasis. In humans, the rapid improvement in
      carbohydrate homoeostasis observed after bypass surgery is secondary to an
      increase in insulin sensitivity rather than an increase in insulin secretion,
      which occurs later. Several mechanisms are involved--disappearance of
      hypertriglyceridaemia and decrease in levels of circulating fatty acids,
      disappearance of the mechanisms of lipotoxicity in the liver and skeletal muscle,
      and increases in secretion of GLP-1 and PYY--and may be intricately linked. In
      the medium term and in parallel with weight loss, a decrease in fatty tissue
      inflammation (which is also seen with restrictive techniques) may also be
      involved in metabolic improvement. Other mechanisms specific to malabsorption
      based techniques (due to the required exclusion of part of the intestine), such
      as changes in the activity of digestive vagal afferents, changes in intestinal
      flora and stimulation of intestinal neoglucogenesis, also need to be studied in
      greater detail. The intestine is, thus, a key organ in the regulation of
      glycaemic equilibrium and may even be involved in the pathophysiology of type 2
      diabetes.

PMID- 20152735
TI  - The effect of bariatric surgery on gut hormones that alter appetite.
AB  - Bariatric surgery is the only effective treatment for morbid obesity in the long
      term. Gut hormones are key players in the metabolic mechanisms causing obesity.
      Furthermore gut hormones are involved in the signalling process of hunger and
      satiety which leads to the control of nutrient intake. In this review, the role
      of these hormones as facilitators of appetite control after bariatric and
      metabolic surgery will be explored.

PMID- 20152737
TI  - Mechanisms of early improvement/resolution of type 2 diabetes after bariatric
      surgery.
AB  - Bariatric surgery represents the main option for obtaining substantial and long
      term weight loss in morbidly obese subjects. In addition, malabsorptive
      (biliopancreatic diversion, BPD) and restrictive (roux-en-Y gastric bypass, RYGB)
      surgery, originally devised to treat obesity, has also been shown to help
      diabetes. Indeed, type 2 diabetes is improved or even reversed soon after these
      operations and well before significant weight loss occurs. Two hypotheses have
      been proposed to explain the early effects of bariatric surgery on diabetes-
      namely, the hindgut hypothesis and the foregut hypothesis. The former states that
      diabetes control results from the more rapid delivery of nutrients to the distal
      small intestine, thereby enhancing the release of hormones such as glucagon-like
      peptide-1 (GLP-1). The latter theory contends that exclusion of the proximal
      small intestine reduces or suppresses the secretion of anti-incretin hormones,
      leading to improvement of blood glucose control as a consequence. In fact,
      increased GLP-1 plasma levels stimulate insulin secretion and suppress glucagon
      secretion, thereby improving glucose metabolism. Recent studies have shown that
      improved intestinal gluconeogenesis may also be involved in the amelioration of
      glucose homoeostasis following RYGB. Although no large trials have specifically
      addressed the effects of bariatric surgery on the remission or reversal of type 2
      diabetes independent of weight loss and/or caloric restriction, there are
      sufficient data in the literature to support the idea that this type of surgery-
      specifically, RYGB and BPD--can lead to early improvement of glucose control
      independent of weight loss.

PMID- 20152736
TI  - Effect of gastric bypass surgery on the incretins.
AB  - AIMS: Our studies were designed to understand the role of the gut hormones
      incretins GLP-1 and GIP on diabetes remission after gastric bypass surgery (GBP).
      METHODS: Morbidly obese patients with type 2 diabetes (T2DM) were studied before
      and 1, 6, 12, 24 and 36 months after GBP. A matched group of patients were
      studied before and after a diet-induced 10 kg weight loss, equivalent to the
      weight loss 1 month after GBP. All patients underwent an oral glucose tolerance
      test and an isoglycaemic glucose intravenous challenge to measure the incretin
      effect. RESULTS: Post-prandial GLP-1 and GIP levels increase after GBP and the
      incretin effect on insulin secretion normalizes to the level of non diabetic
      controls. In addition, the pattern of insulin secretion in response to oral
      glucose changes after GBP, with recovery of the early phase, and post-prandial
      glucose levels decrease significantly. These changes were not seen after an
      equivalent weight loss by diet. The changes in incretin levels and effect
      observed at 1 month are long lasting and persist up to 3 years after the surgery.
      The improved insulin release and glucose tolerance after GBP were shown by others
      to be blocked by the administration of a GLP-1 antagonist in rodents,
      demonstrating that these metabolic changes are, in part, GLP-1 dependent.
      CONCLUSION: Although sustained and significant weight loss is likely to be the
      key mediator of diabetes remission after GBP, the changes of incretins improve
      the early phase of insulin secretion and post-prandial glucose levels, and
      contribute to the better glucose tolerance.

PMID- 20152738
TI  - Laparoscopic adjustable gastric banding and laparoscopic sleeve gastrectomy:
      which has a place in the treatment of diabetes in morbidly obese patients?
AB  - Laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve
      gastrectomy (LSG) are two bariatric procedures approved for the management of
      morbidly obese patients. According to a meta-analysis of all obese patients who
      underwent bariatric procedures, 11% also had type 2 diabetes mellitus (T2DM)
      before surgery, and improvement or resolution of this co-morbidity was
      highlighted in many of the studies. However, the mechanism(s) of action
      underlying such an effect with the various types of bariatric procedure remain
      unclear. Also, in terms of weight loss, the most efficient operations are those
      that come with a high rate of morbidity. This means that the choice of procedure
      is best done after a multidisciplinary team discussion with the patient in an
      effort to predict the beneficial effects and risks of each possible procedure.
      However, for years now, the bariatric team at Montpellier Hospital has preferred
      either LSG or LGBP as the treatment of choice for morbidly obese patients with
      T2DM, given the higher rates of failure with LAGB over time compared with the
      excellent results achieved by both LSG and LGBP in many studies.

PMID- 20152739
TI  - Gastric bypass and glucose metabolism.
AB  - Gastric bypass (GBP) surgery was originally developed to treat patients with
      severe obesity. Nevertheless, in those with type 2 diabetes, GBP also exerts a
      spectacular effect on glucose metabolism, leading to remission of the diabetes in
      many cases. In this report, the basic principles of the surgical procedure are
      outlined together with a summary of the potential mechanisms that might explain
      the remarkable effects of this type of operation on glucose metabolism.

PMID- 20152740
TI  - Bariatric surgery in young massively obese diabetic patients.
AB  - Obesity is the most important lifestyle-related risk factor for type 2 diabetes
      (T2DM). The prevalence of T2DM in adolescents is increasing in parallel with the
      increasing incidence of major obesity. In adult obese subjects, the greatest
      degree of T2DM prevention, improvement or recovery has been reported in patients
      who have undergone bariatric surgery. However, few studies are available on the
      benefits and risks of bariatric surgery in adolescents with T2DM. The indications
      for obesity surgery in this population are unusual, and should only be considered
      in academic settings after comprehensive interdisciplinary evaluation.

PMID- 20152741
TI  - Bariatric surgery in patients with type 2 diabetes: benefits, risks, indications
      and perspectives.
AB  - Obesity plays a key role in the pathophysiology of type 2 diabetes (T2DM), and
      weight loss is a major objective, although difficult to achieve with medical
      treatments. Bariatric surgery has proven its efficacy in obtaining marked and
      sustained weight loss, and is also associated with a significant improvement in
      glucose control and even diabetes remission. Roux-en-Y gastric bypass appears to
      be more effective in diabetic patients than the restrictive gastroplasty
      procedure. This may be explained not only by greater weight reduction, but also
      by specific hormonal changes. Indeed, increased levels of glucagon-like peptide-1
      (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) may lead to
      improved beta-cell function and insulin secretion as well as reduced insulin
      resistance associated with weight loss. The presence of T2DM in obese individuals
      is a further argument to propose bariatric surgery, and even more so when
      diabetes is difficult to manage by medical means and other weight-related
      complications may occur. Bariatric surgery is associated with a better
      cardiovascular prognosis and reduced mortality, even though acute and long-term
      complications are present. The observation that surgical rerouting of nutrients
      triggers changes in the release of incretin hormones that, in turn, ameliorate
      the diabetic state in the absence of weight loss has led to the recent
      development of innovative surgical procedures. Thus, bariatric surgery may be
      said to be progressing towards so-called 'metabolic surgery', which merits
      further evaluation in patients with T2DM within a multidisciplinary approach that
      involves both surgeons and endocrinologists.

PMID- 20152742
TI  - Medical follow up after bariatric surgery: nutritional and drug issues. General
      recommendations for the prevention and treatment of nutritional deficiencies.
AB  - This review is an update of the long-term follow-up of nutritional and metabolic
      issues following bariatric surgery, and also discusses the most recent guidelines
      for the three most common procedures: adjustable gastric bands (AGB); sleeve
      gastrectomy (SG); and roux-en-Y gastric bypass (GBP). The risk of nutritional
      deficiencies depends on the percentage of weight loss and the type of surgical
      procedure performed. Purely restrictive procedures (AGB, SG), for example, can
      induce digestive symptoms, food intolerance or maladaptative eating behaviours
      due to pre- or postsurgical eating disorders. GBP also has a minor malabsorptive
      component. Iron deficiency is common with the three types of bariatric surgery,
      especially in menstruating women, and GBP is also associated with an increased
      risk of calcium, vitamin D and vitamin B12 deficiencies. Rare deficiencies can
      lead to serious complications such as encephalopathy or protein-energy
      malnutrition. Long-term problems such as changes in bone metabolism or
      neurological complications need to be carefully monitored. In addition, routine
      nutritional screening, recommendations for appropriate supplements and monitoring
      compliance are imperative, whatever the bariatric procedure. Key points are: (1)
      virtually routine mineral and multivitamin supplementation; (2) prevention of
      gallstone formation with the use of ursodeoxycholic acid during the first 6
      months; and (3) regular, life-long, follow-up of all patients. Pre- and
      postoperative therapeutic patient education (TPE) programmes, involving a new
      multidisciplinary approach based on patient-centred education, may be useful for
      increasing patients'long-term compliance, which is often poor. The role of the
      general practitioner has also to be emphasized: clinical visits and follow-ups
      should be monitored and coordinated with the bariatric team, including the
      surgeon, the obesity specialist, the dietitian and mental health professionals.

PMID- 20152743
TI  - Medical management of diabetes after bariatric surgery.
AB  - Several studies indicate that bariatric surgery frequently leads to resolution or
      improvement of type 2 diabetes in overweight patients. However, the medical
      postoperative management requires lifelong counselling, monitoring and nutrient
      supplements in patients in remission as well as in patients who continue to be
      diabetic. The aim of such management is to avoid nutritional deficiencies, and to
      delay diabetes relapse by optimizing the control of risk factors. To this end,
      diet and pharmacological prescriptions, including vitamin and mineral
      supplements, are indispensable, despite the fact that specific recommendations,
      until now, have been lacking for these particular patients.

PMID- 20152744
TI  - Bariatric surgery for diabetes treatment: why should we go rapidly to surgery.
AB  - Surgical treatment of morbid obesity has been shown to be efficient for long-term
      weight loss and to improve obesity-related complications. The improvement of type
      2 diabetes (T2DM) is dependent of the type of surgery, and is more frequent with
      gastric bypass than with gastric band. Normalization of glucose metabolism is
      rapid, often occurring before weight loss, and shown to be related to both a
      decrease in insulin resistance and an increase in insulin secretion. Some factors
      limiting the efficiency of gastric bypass on T2DM is the duration of diabetes and
      the residual beta-cell mass. However, a decrease in diabetes-related death has
      been found in a large series of surgical cases. These data constitute a good
      argument for proposing surgery in T2DM obese patients as soon as possible.
      Nevertheless, whether or not this suggests changing the usual indications for
      bariatric surgery in T2DM patients, such as a body mass index (BMI) score of<35
      kg/m(2), remains controversial.

PMID- 20152745
TI  - Bariatric surgery in patients with late-stage type 2 diabetes: expected
      beneficial effects on risk ratio and outcomes.
AB  - AIM: The objective of this review was to assess the safety and efficacy of
      bariatric surgery in patients with severe obesity and late-stage type 2 diabetes
      (T2D). METHODS: A review of the literature looked for reported data on outcomes
      of bariatric surgery when performed in patients with T2D treated by oral
      medications or insulin. Recent updates in our understanding of the effects of
      bariatric surgery on glucose homoeostasis were also examined. RESULTS: Data on
      the outcomes of bariatric surgery in advanced T2D are scarce. Having either T2D
      for more than 10 years or more advanced forms of the disease, according to
      antidiabetic therapy, is associated with less weight loss after bariatric
      surgery. Improvement of diabetes control is also less than seen in earlier forms
      of T2D, and resolution of the disease is less likely to occur. However, a
      reduction in oral medications or insulin doses has been documented. Residual beta
      cell function is suggested to be a possible determining factor for therapeutic
      changes or cessation, while reductions in both weight-related and non-weight
      related insulin resistance can be expected. Beneficial effects on co-morbidities
      and overall mortality due to the excess weight loss may also be seen. CONCLUSION:
      Bariatric surgery in patients with severe obesity and late-stage T2D is currently
      justified by the expected benefits due to the excess weight loss. However,
      specific studies are needed to better assess the effects of such surgery on
      glucose control and the associated outcomes.

PMID- 20152746
TI  - About the pathogenesis of the so-called adult acquired pes planus.
AB  - Even overlooking the scarcely significance nature of the term "flat", in the
      pathogenesis of the adult acquired flat foot deformity, we must consider also the
      spring ligament degenerative pathology, that I called "degenerative glenopathy",
      due to its reference to the glenoid, without a primitive posterior tibial tendon
      disease. The glenoid structure intervenes in the cotyloid structure (acetabulum)
      of the "coxa pedis". In many cases the aetiological moment must be clarified
      finding of the accessory navicular bone. Its position between the posterior
      tibial tendon and glenoid explains a possible direct microtraumatic lesional
      mechanism.

PMID- 20152747
TI  - The efficacy of the tourniquet in foot and ankle surgery? A systematic review and
      meta-analysis.
AB  - Tourniquets are commonly used during foot and ankle surgery. The purpose of this
      study was to compare the peri- and post-operative outcomes of tourniquet-assisted
      to non-tourniquet-assisted ankle and foot surgery. A systematic review was
      undertaken assessing the electronic databases Medline, CINAHL, AMED and EMBASE,
      in addition to a review of unpublished material and a hand search of pertinent
      orthopaedic journals. The evidence-base was critically appraised using the
      Cochrane Bone, Joint and Muscle Trauma Group quality assessment tool. Study
      heterogeneity was measured using chi(2) and I(2) statistics. Where appropriate, a
      random-effects meta-analysis was undertaken to pool results of primary studies,
      assessing mean difference or relative risk of each outcome. A total of four
      studies were identified. The findings of this study would suggest that hospital
      length of stay was significantly shorter, and that the post-operative period was
      less painful, with reduced swelling from the fifth post-operative day, in
      surgeries undertaken without a tourniquet, compared to tourniquet-assisted
      procedures. There may be a greater incidence of wound infection and deep vein
      thrombosis in tourniquet-assisted foot and ankle procedures. The methodological
      quality of the evidence base is limited. Further study is required to address
      these limitations, after which we may be able to determine whether a tourniquet
      should be used during ankle or foot procedures.

PMID- 20152748
TI  - Closed wedge osteotomy in 66 patients for the treatment of moderate to severe
      hallux valgus.
AB  - BACKGROUND: The intention of this study was to analyze the long-term results of
      the proximal closing wedge osteotomy for the correction of hallux valgus
      deformity, modified by adding a mini L-plate for osteosynthesis. METHODS: The
      outcome of a proximal first metatarsal closing wedge osteotomy was
      retrospectively evaluated after a mean follow-up of 52 months. A total of 66
      female patients (86 feet) participated in this study. The AOFAS-score was used to
      evaluate the postoperative results. Pre- and postoperative weight-bearing
      radiographs were used to evaluate the osseous development. RESULTS: 95.5% of the
      patients were satisfied, 3 patients (4.5%) were not satisfied with the overall
      result of the operation. Transfer metatarsalgia was registered in 7 of 50 cases.
      The mean improvement of the HV-angle was 22.1 degrees (36.4 degrees to 14.3
      degrees ) and the intermetatarsal angle was reduced from a mean of 17.6 degrees
      to a mean of 6.5 degrees . The mean first metatarsal shortening was 3.2mm. The
      mean AOFAS-score was 78 points. CONCLUSION: The results confirm, that the closing
      wedge osteotomy is indicated for moderate to severe hallux valgus. The shortening
      of the first ray is comparable with other well-established operative procedures.
      The risk of transfer metatarsalgia can only be lightly reduced by this procedure.

PMID- 20152749
TI  - The management and outcome of lateral process fracture of the talus.
AB  - BACKGROUND: Lateral process fractures of the talus are a rare injury with
      significant associated morbidity when missed. Only a small number of case series'
      and reports are available and the appropriate management of these fractures is
      not really known. METHODS: We reviewed available English language literature for
      reports and series of lateral process fractures of talus. Only papers in which
      the classification of fracture, management and outcome were clear were included
      in our analyses. RESULTS: 109 Cases in total were identified including four cases
      from a personal series. 50 Type I, 17 type II and 29 type III fractures were
      analysed. A significant number of patients required late surgery when the
      diagnosis was initially missed. CONCLUSION: Type I fractures are best treated
      with ORIF, type II with excision and type III with casting. Fractures presenting
      late that are not united should be excised if small and internally fixed if
      large.

PMID- 20152750
TI  - Foot pressure differences in men and women.
AB  - BACKGROUND: Women and men are anatomically and physiologically different in a
      number of ways. Anthropometric studies have shown considerable differences in the
      foot bones of both genders. These differences could potentially mean different
      foot pressures in men and women. OBJECTIVE: The aim of our study was to
      investigate any potential foot pressure differences between males and females
      using the Pedar-M (Novel gmbh, Germany) in-shoe foot pressure measurement system.
      METHODS: Twenty-eight subjects (16 females and 12 males) were recruited. Peak
      pressure, contact area, contact time, pressure-time integral, force-time
      integral, instant of peak pressure, maximum force and mean force were recorded
      and subsequently analysed. RESULTS: In males, contact area was significantly
      larger in all regions of the foot compared with females. There were no
      significant between gender differences in peak pressure, contact time, pressure
      time integral and instant of peak pressure. Force-time integral was significantly
      greater in males than females under the 1st, 3rd, and 4th metatarsal heads.
      Maximum force was also significantly higher in males under the heel, 1st and 3rd
      metatarsal heads. Mean force was greater in males under the 3rd metatarsal head.
      CONCLUSION: There were no peak pressure differences; however the contact area of
      the male foot was larger than that in females.

PMID- 20152751
TI  - Survivorship of the bio-action metatarsophalangeal joint arthroplasty for hallux
      rigidus: 5-year follow-up.
AB  - BACKGROUND: Metatarsophalangeal joint arthroplasty is an accepted treatment for
      hallux rigidus. There are few reports of the long-term results of this procedure.
      METHODS: A series of 15 consecutive bio-action first metatarsophalangeal total
      joint replacements were retrospectively reviewed after a minimum follow-up of 5
      years. The patients were assessed using the American Orthopaedic Foot and Ankle
      Society Score. Patient satisfaction and standard radiographs were also examined.
      RESULTS: Subjectively, just over half the patients were satisfied with the
      results of the surgery. Objectively, however mechanical failure of the implant
      was universal, as determined radiographically. DISCUSSION: Despite some success
      in relieving symptoms in patients, we have abandoned this procedure because of
      the high and increasing rate of failure, as demonstrated both clinically and
      radiologically.

PMID- 20152752
TI  - Surgical tip: Repair of acute Achilles rupture with Krackow suture through a 1.5
      cm medial wound.
AB  - Acute Achilles tendon ruptures is one of the commonest tendon injury of the foot
      and ankle. The management of this problem is still controversial. Treatment can
      be classified into non-surgical and surgical types. Surgical management can be
      subdivided into open repair, percutaneous with or without adjunct of arthroscopy.
      In compare with non-surgical management, surgical management will decrease the
      tendon re-rupture rate. However, the possible surgical complications including
      wound breakdown and sural nerve injury are still quite significant. Percutaneous
      repair technique has the advantage of less chance of wound breakdown, but the
      rate of tendon re-rupture is higher than that after open tendon repair, because
      the repair is usually weaker than that achieved in open repair. Lui have
      described an endoscopic assisted repair with the Krackow locking suture. However,
      the technique is complicated and six portal wounds are needed. A simpler way of
      applying the Krackow suture through the portal wound has been described for
      reattachment of Achilles tendon insertion after endoscopic calcaneoplasty. We
      describe a mini-open approach of Achilles tendon repair with the Krackow locking
      suture. By means of release of the medial edge of the investing fascia, the
      Achilles tendon can be mobilized easily and the Krackow locking suture can be
      applied through a 1.5cm medial wound. Hopefully, this can improve the strength of
      repair and maintaining the advantage of minimally invasive tendon repair.

PMID- 20152753
TI  - Arthrodesis of the first metatarsophalangeal joint with ball and cup reamers and
      osteosynthesis with pure titanium staples Radiological evaluation of a continuous
      series of 54 cases.
AB  - BACKGROUND: In a continuous series of 54 MTP-1 arthrodeses using ball and cup
      reamers, fusion and great toe position were analyzed. MATERIALS AND METHODS: The
      population was mainly female (46 versus 8). Mean age at operation was 61 years.
      Arthrodesis was for four conditions of symptomatic degenerative disease: 36
      severe hallux valgus (>35 degrees ), 7 recurrences of hallux valgus, 9 hallux
      rigidus and 2 hallux varus. Arthrodesis used a medial approach, articular surface
      preparation by ball and cup reamers (plus perforation by Kirschner wire), and
      osteosynthesis with three titanium staples. Pre- and postoperative big toe
      positions were analysed with the Footlog semi-automated X-ray assessment
      software. RESULTS: All patients were followed up for a mean 38.6 months (22-56).
      Overall fusion rate was 94.4%, and 99% for primary arthrodesis. Mean time to
      union was 56 days (74% in 6 weeks), with 3 non-unions (5.6%), including 2 after
      hallux valgus recurrence. Mean pre-operative toe valgus was 40 degrees and 14.1
      degrees at revision for all groups. 95% of arthrodeses fused at a mean lateral
      metatarsophalangeal angle of 22.6 (18-26 degrees ). Metatarsus varus exceeded 20
      degrees in 8 cases, mainly in the severe hallux valgus group; at revision, the
      mean first intermetatarsal angle was 10.6 degrees (9-12 degrees ). CONCLUSION:
      Arthrodesis of the first metatarsophalangeal joint with ball and cup reamers is a
      reliable and reproducible technique, giving total correction of big toe valgus.
      The first intermetatarsal angle was corrected without supplementary osteotomy.
      Using three pure titanium staples for fixation, rate and time of fusion were in
      line with reference techniques.

PMID- 20152754
TI  - Complete subtalar release for older children who had recurrent clubfoot
      deformity.
AB  - BACKGROUND: Neglected idiopathic clubfoot deformities, and severe recurrent
      deformity after previous surgery presents technical difficulties for correction
      and challenges for surgeons to achieve primary skin closure. METHODS: Between
      2000 and 2006, 18 children (30 feet), had complete subtalar release (CSTR) for
      failed previous surgery in 28 feet and severe neglected congenital talipes
      equinovarus (CTEV) in 2 feet followed by cross leg fasciocutaneous flaps for
      reconstruction of residual defect at the ankle and foot after full correction of
      the deformity. Mean patients followed up were 4.5 years (average 2-8 years). 23
      feet were classified as Dimeglio III and 7 feet as Dimeglio IV. RESULTS: All
      cases achieved a plantigrade foot, better walking ability (p<0.03), and parental
      satisfaction with the result (p<0.001). Ankle joint doriflexion increased from
      mean (-21.33 degrees ) preoperatively to (12.5 degrees ) postoperatively. All
      cases showed postoperative improvement in their radiographic findings. The mean
      preoperative talocalcaneal angle increased from (15.7 degrees to 30.03 degrees ).
      The talo-first metararsal angle improved from a preoperative mean of -16 degrees
      mean of 5.53 degrees postoperatively. At the final follow-up cosmetically
      acceptable plantigrade foot was achieved in all feet. Four legs (14.28%)
      developed hypertrophic scars at the donar flap site. One patient developed 1.5cm
      marginal necrosis of the flap, which did heal after debridement by secondary
      intention. None of the feet had recurrence at the final follow up. Despite the
      enormous improvement clinically and radiologically, their was no statistical
      significant difference between preoperative and postoperative radiological angles
      (p<0.069). The number of previous surgical interventions had no influence on the
      outcome. All the previously treated feet had inadequate release of important
      tethered soft tissue. CONCLUSION: This is indicative of the enormous value of
      complete subtalar release combined with cross leg fasciocutaneous flap without
      the need for bony intervention in previously operated failed feet or neglected
      deformities.

PMID- 20152755
TI  - Overuse ankle injuries in professional Irish dancers.
AB  - BACKGROUND: Overuse ankle injuries have been described in elite athletes and
      professional ballet dancers however the spectrum of injuries experienced by
      professional Irish dancers has not been defined. METHODS: A troupe of actively
      performing dancers from an Irish-dance show were recruited (eight male, ten
      female; mean age, 26 years). The prevalence of overuse injuries in the right
      ankle was determined from magnetic resonance imaging. Foot and ankle self-report
      questionnaires were also completed (AOFAS and FAOS). RESULTS: Only three ankles
      were considered radiologically normal. Achilles tendinopathy, usually
      insertional, was the most frequent observation (n=14) followed by plantar
      fasciitis (n=7), bone oedema (n=2) and calcaneocuboid joint degeneration (n=2).
      There were limited correlations between MRI patterns and clinical scores
      indicating that many conditions are sub-clinical. Dancers with ankle pain had
      poor low (p=0.004) and high (p=0.013) level function. CONCLUSIONS: Overuse ankle
      injuries are common in Irish dancers. Incorporating eccentric exercises and
      plantar fascia stretching into a regular training program may benefit this
      population.

PMID- 20152756
TI  - Role of early surgical revascularization in the management of refractory diabetic
      foot ulcers in patients without overt ischemic limbs.

PMID- 20152758
TI  - The sum is greater than the parts.

PMID- 20152759
TI  - Drinking ourselves into oblivion?

PMID- 20152760
TI  - Targeting the target: a step forward for the treatment of non-small-cell lung
      cancer.

PMID- 20152761
TI  - Immunity unleashed in melanoma.

PMID- 20152762
TI  - Patient access schemes for high-cost cancer medicines.

PMID- 20152763
TI  - Risk of bleeding not increased by sorafenib or sunitinib.

PMID- 20152766
TI  - Lateral pelvic lymph-node dissection: still an option for cure.

PMID- 20152767
TI  - Histological subtype of gastric cancer in Japan.

PMID- 20152768
TI  - Resection of colorectal liver metastases: only for younger patients?

PMID- 20152769
TI  - Ki67 in breast cancer: prognostic and predictive potential.
AB  - The leading parameters that define treatment recommendations in early breast
      cancer are oestrogen-receptor, progesterone-receptor, and human epidermal growth
      factor status. Although some pathologists report Ki67 in addition to other
      biological markers, the existing guidelines of the American Society of Clinical
      Oncology do not include Ki67 in the list of required routine biological markers.
      The advent of new genetic tests has emphasised the role of proliferative genes,
      including Ki67, as prognostic and predictive markers. Additionally, randomised
      studies have retrospectively reviewed data and reported on the role of Ki67 in
      breast cancer. In light of new data, we have re-assessed evidence that could
      change guidelines to include Ki67 in the standard pathological assessment of
      early breast cancers. This review provides an update on the current knowledge on
      Ki67 and of the evidence in the published work about the prognostic and
      predictive role of this marker, and provides information on the laboratory
      techniques used to determine Ki67.

PMID- 20152770
TI  - Ewing's sarcoma.
AB  - Progress in the treatment of Ewing's sarcoma, the second most common bone tumour
      in children and adolescents, has improved survival from about 10% in the period
      before chemotherapy was introduced to about 75% today for patients with localised
      tumours. However, patients with metastases still fare badly, and the therapy
      carries short-term and long-term toxicities. Multidisciplinary care is
      indispensable for these patients. Molecular techniques and new imaging modalities
      are affecting the diagnosis and classification of patients with Ewing's sarcoma.
      Cooperative group studies have led to chemotherapy regimens using the same drugs
      (vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide), although
      the exact regimens differ in Europe and North America. The EWS-ETS family of gene
      fusions and their downstream effects in Ewing's sarcomas provide opportunities
      for new approaches to treatment. These include the inhibition of the fusion gene
      or its protein product, and pathways related to IGF1 and mTOR. Inhibition of
      tyrosine kinases, exploitation of non-apoptotic cell death, and interference with
      angiogenesis are promising new approaches. With many new approaches and
      relatively few patients, it will be challenging to integrate new and established
      treatments through clinical trials.

PMID- 20152771
TI  - The metabolic syndrome in cancer survivors.
AB  - The metabolic syndrome, as a cluster of cardiovascular risk factors, may
      represent an important connection between cancer treatment and its common late
      effect of cardiovascular disease. Insight into the aetiology of the metabolic
      syndrome after cancer treatment might help to identify and treat cancer survivors
      with increased cardiovascular risk. In this review, we summarise current
      knowledge on the prevalence and pathophysiology of the metabolic syndrome in
      cancer survivors, and discuss current intervention strategies with an emphasis on
      new developments.

PMID- 20152773
TI  - Reconsideration of assessment of the quality of studies on accuracy of screening
      instruments to identify aberrant drug-related behaviors in patients prescribed
      opioids.

PMID- 20152772
TI  - Teleoncology: current and future applications for improving cancer care globally.
AB  - Access to quality cancer care is often unavailable in low-income and middle
      income countries, and also in rural or remote areas of high-income countries.
      Teleoncology-oncology applications of medical telecommunications, including
      pathology, radiology, and other related disciplines-has the potential to enhance
      access to and quality of clinical cancer care, and to improve education and
      training. Implementation of teleoncology in the developing world requires an
      approach tailored to priorities, resources, and needs. Teleoncology can best
      achieve its proposed goals through consistent and long-term application. We
      review teleoncology initiatives that have the potential to decrease cancer-care
      inequality between resource-poor and resource-rich institutions and offer
      guidelines for the development of teleoncology programmes in low-income and
      middle-income countries.

PMID- 20152775
TI  - Effects of cxytocin and prolactin on stress-induced bladder hypersensitivity in
      female rats.

PMID- 20152777
TI  - A weighty subject.

PMID- 20152778
TI  - A vision science reality check.

PMID- 20152779
TI  - Ocular manifestations uncover chronic subdural hematoma secondary to abuse.
AB  - BACKGROUND: An abduction deficit or cranial nerve VI palsy can have many
      potential etiologies. However, a cranial nerve VI palsy in the setting of disc
      edema suggests increased intracranial pressure, requiring emergent work-up. CASE
      REPORT: An 18-year-old woman presented with significant headaches and horizontal
      diplopia, which she claimed began after giving birth 3 months prior. Her
      examination found a right cranial nerve VI palsy and mild disc edema of the left
      eye. This combination of findings was suggestive of increased intracranial
      pressure. Emergent workup uncovered a large chronic subdural hematoma requiring
      immediate neurosurgical intervention. She ultimately admitted to being abused by
      her partner. CONCLUSION: Diplopia and disc edema in a young, nonoverweight
      patient with an altered mental state is very concerning. Meningitis and
      complications of spinal anesthesia, although rare, need to be considered in
      patients who have recently given birth. However, other causes of increased
      intracranial pressure, including subdural hemorrhage secondary to trauma, also
      have to be considered, even if the patient denies any history of trauma. Abused
      patients often deny trauma.

PMID- 20152780
TI  - Through our children's eyes--the public health impact of the vision screening
      requirements for Indiana school children.
AB  - BACKGROUND: The vision screening of preschool and school children is a widely
      accepted procedure to detect vision problems that can interfere with learning.
      The Indiana General Assembly requires the annual vision screening with the
      Modified Clinical Technique (MCT) of all children upon their enrollment in either
      kindergarten or the first grade, with the exception of schools that apply for and
      receive waivers to conduct only a distance Snellen chart screening. METHODS: In
      association with the Indiana State Department of Health, the Indiana University
      School of Optometry conducted an analysis of statewide school screening data on
      36,967 grade 1 children from 139 of the 294 Indiana school corporations that
      submitted data for the 2000-2001 school year to examine differences in referral
      rate by screening method, the socioeconomic status of children screened, and
      academic performance. RESULTS: The MCT was used by 125 of the school
      corporations, and some other technique was used by 14 school corporations.
      Significant differences were seen when comparing the mean referral rates of
      school corporations that conduct the MCT against school corporations that do not
      conduct the MCT (P = 0.001) and in the rate of referral by median family income
      of the children screened (P = 0.050). A median family income of $46,500 was
      identified as the level at which the income-specific difference in referral rates
      ceased to be significant (P = 0.074). In spite of an observed tendency toward a
      higher referral rate for children who performed below average on the standardized
      Indiana Statewide Testing for Educational Progress Plus (ISTEP+) exam, results
      were found to be not significant (P = 0.116) when comparing the percentage of
      grade 1 children referred to an eye care provider in 2000-2001 with their
      percentages of passing both the English/language arts and mathematics components
      of the 2002-2003 ISTEP+ exam (in grade 3). CONCLUSION: Schools using the highly
      sensitive and specific MCT identified more visually at-risk children than schools
      using alternative, less sensitive vision screening techniques, and the percentage
      of grade 1 children referred to an eye care provider was higher for school
      corporations with lower median family incomes. Although statistically
      insignificant, the results indicate that students who fail the vision screening
      in grade 1 tend to be more at risk for poorer academic performance on
      standardized testing in grade 3.

PMID- 20152781
TI  - A series of 3 cases of corneal abrasion with multiple etiologies.
AB  - BACKGROUND: Most corneal abrasions are caused by mechanical injuries affecting
      the superficial epithelial layer. Although one of the functions of the eyelid is
      to protect the eye, its reaction time of about 425 msec is slower than many
      ocular insults; thus, corneal abrasions are among the most commonly occurring eye
      emergencies. CASE REPORTS: Three cases of corneal abrasions with different
      etiologies are presented. The first case was a large abrasion of the cornea near
      the visual axis caused by a wood chip. A metal foreign body with rust was lodged
      in the cornea from metal grinding in the second case. The third case was
      iatrongenically induced by an A-scan probe while a fellow student was measuring
      the axial length of the eye. CONCLUSION: Corneal abrasions are one of the most
      common ocular conditions presented to eye clinics or emergency departments.
      Although there are different etiologies of abraded corneal epithelium, current
      clinical management for most corneal abrasions involves a bandage contact lens,
      use of topical antibiotics, and cycloplegics. Large and central corneal
      abrasions, however, warrant a consultation with a corneal specialist.

PMID- 20152782
TI  - Implantable miniature telescope: lessons learned.
AB  - BACKGROUND: The Implantable Miniature Telescope (IMT) is a telescopic prosthesis
      that, combined with the optics of the cornea, constitutes an intraocular
      magnifying system. It is indicated for use in patients with stable, nonfoveal
      sparing, bilateral, stable, age-related macular degeneration (end-stage) with
      associated scotomas. The telescope prosthesis is implanted in only one of the
      patient's eyes. In this way, the implanted eye provides improved visual acuity,
      and the nonimplanted eye continues to provide peripheral vision for ambulation.
      Two hundred seventeen patients with end-stage AMD were enrolled in a prospective,
      multicenter, open-label trial (IMT-002) beginning in 2003. The implanted eye was
      the worse eye for most patients based on a selection rule set by the U.S. Food
      and Drug Administration (FDA) protocol; however, in most cases (90%), visual
      acuity improvement goals were met with the device. This report will
      retrospectively look at 2 selected patients implanted at the Emory Eye Center in
      Atlanta as part of that trial to derive lessons for subject and eye selection
      criteria. CASE REPORTS: Two cases were selected to represent patients' levels of
      functional success and satisfaction. Determination of their visual and functional
      outcome at 1-year postimplantation was based on best-corrected visual acuity and
      the National Eye Institute Visual Functioning Questionnaire 25-Item quality-of
      life survey. Four years after implantation, 1 patient continued to use the
      telescope prosthesis eye for all visual activities; the other patient did not
      perceive any benefit from the device and continued to primarily use the fellow
      nonimplanted eye. The benefit of the telescopic prosthesis was most likely
      accounted for by the level of visual acuity in both eyes postimplantation and eye
      dominance. CONCLUSION: Proper eye selection chosen for implantation with the
      telescope prosthesis appears to be an important if not critical factor in
      determining patient satisfaction for visual processing and functional success.
      Based on the author's experience with the IMT, optometrists can aid the
      multidisciplinary team by preoperatively determining which eye, if implanted,
      offers the optimal potential functional benefit for appropriate candidates.

PMID- 20152783
TI  - Screening athletes with Down syndrome for ocular disease.
AB  - BACKGROUND: Persons with Down syndrome are well known to have a high prevalence
      of vision and eye health problems, many of which are undetected or untreated
      primarily because of infrequent ocular examinations. Public screening programs,
      directed toward the pediatric population, have become more popular and commonly
      use letter or symbol charts. This study compares 2 vision screening methods, the
      Lea Symbol chart and a newly developed interactive computer program, the
      Vimetrics Central Vision Analyzer (CVA), in their ability to identify ocular
      disease in the Down syndrome population. METHODS: Athletes with Down syndrome
      participating in the European Special Olympics underwent an ocular screening
      including history, auto-refraction, colour vision assessment, stereopsis
      assessment, motility assessment, pupil reactivity, and tonometry testing, as well
      as anterior segment and fundus examinations to evaluate for ocular disease.
      Visual acuity was tested with the Lea chart and CVA to evaluate these as
      screening tests for detecting ocular disease as well as significant, uncorrected
      refractive errors. RESULTS: Among the 91 athletes that presented to the
      screening, 79 (158 eyes) were sufficiently cooperative for the examination to be
      completed. Mean age was 26 years +/-10.8 SD. Significant, uncorrected refractive
      errors (>/=1.00 spherical equivalent) were detected in 28 (18%) eyes and ocular
      pathology in 51 (32%) eyes. The Lea chart sensitivity and specificity were 43%
      and 74%, respectively, for detecting ocular pathology and 58% and 100% for
      detecting uncorrected refractive errors. The CVA sensitivity and specificity were
      70% and 86% for detecting pathology and 71% and 100% for detecting uncorrected
      refractive errors. CONCLUSION: This study confirmed the findings of prior studies
      in identifying a significant presence of uncorrected refractive errors and ocular
      pathology in the Down syndrome population. Screening with the Lea symbol chart
      found borderline sufficient sensitivity and specificity for the test to be used
      for screening in this population. The better sensitivity and specificity of the
      CVA, if adjusted normative values are utilized, appear to make this test
      sufficient for testing Down syndrome children for identifying both refractive
      errors and ocular pathology.

PMID- 20152784
TI  - Vision and the hypothalamus.
AB  - For nearly 2 millennia, signs of hypothalamic-related vision disorders have been
      noticed as illustrated by paintings and drawings of that time of undiagnosed
      Horner's syndrome. It was not until the 1800s, however, that specific connections
      between the hypothalamus and the vision system were discovered. With a fuller
      elaboration of the autonomic nervous system in the early to mid 1900s, many more
      pathways were discovered. The more recently discovered retinohypothalamic tracts
      show the extent and influence of light stimulation on hypothalamic function and
      bodily processes. The hypothalamus maintains its myriad connections via neural
      pathways, such as with the pituitary and pineal glands; the chemical messengers
      of the peptides, cytokines, and neurotransmitters; and the nitric oxide
      mechanism. As a result of these connections, the hypothalamus has involvement in
      many degenerative diseases. A complete feedback mechanism between the eye and
      hypothalamus is established by the retinohypothalamic tracts and the ciliary
      nerves innervating the anterior pole of the eye and the retina. A discussion of
      hypothalamic-related vision disorders includes neurologic syndromes, the lacrimal
      system, the retina, and ocular inflammation. Tables and figures have been used to
      aid in the explanation of the many connections and chemicals controlled by the
      hypothalamus. The understanding of the functions of the hypothalamus will allow
      the clinician to gain better insight into the many pathologies associated between
      the vision system and the hypothalamus. In the future, it may be possible that
      some ocular disease treatments will be via direct action on hypothalamic
      function.

PMID- 20152785
TI  - Pediatrics, war, and children. Foreword.

PMID- 20152786
TI  - Pediatrics, war, and children.

PMID- 20152787
TI  - Do the symptom-based, Rome criteria of irritable bowel syndrome lead to better
      diagnosis and treatment outcomes?

PMID- 20152788
TI  - Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding
      site.
AB  - The ATP-competitive inhibitors dasatinib and nilotinib, which bind to
      catalytically different conformations of the Abl kinase domain, have recently
      been approved for the treatment of imatinib-resistant CML. These two new drugs,
      albeit very efficient against most of the imatinib-resistant mutants of Bcr-Abl,
      fail to effectively suppress the Bcr-Abl activity of the T315I (or gatekeeper)
      mutation. Generating new ATP site-binding drugs that target the T315I in Abl has
      been hampered, amongst others, by target selectivity, which is frequently an
      issue when developing ATP-competitive inhibitors. Recently, using an unbiased
      cellular screening approach, GNF-2, a non-ATP-competitive inhibitor, has been
      identified that demonstrates cellular activity against Bcr-Abl transformed cells.
      The exquisite selectivity of GNF-2 is due to the finding that it targets the
      myristate binding site located near the C-terminus of the Abl kinase domain, as
      demonstrated by genetic approaches, solution NMR and X-ray crystallography. GNF
      2, like myristate, is able to induce and/or stabilize the clamped inactive
      conformation of Abl analogous to the SH2-Y527 interaction of Src. The molecular
      mechanism for allosteric inhibition by the GNF-2 inhibitor class, and the
      combined effects with ATP-competitive inhibitors such as nilotinib and imatinib
      on wild-type Abl and imatinib-resistant mutants, in particular the T315I
      gatekeeper mutant, are reviewed.

PMID- 20152789
TI  - [Expectations of patients with a history of poliomyelitis].

PMID- 20152790
TI  - Mansonella perstans filariasis in Africa.
AB  - Mansonella perstans is a vector-borne human filarial nematode, transmitted by
      tiny blood-sucking flies (biting midges). It is widespread in many parts of Sub
      Saharan Africa and also occurs in parts of Central and South America. Despite the
      commonness of this parasite very few studies have been carried out on its
      epidemiology and on the morbidity resulting from it, and only few thorough drug
      trials have been conducted to look for effective and suitable drugs and drug
      regimens for treatment and control. Here, we review currently available knowledge
      on M. perstans infections in Africa, including documented aspects of biology,
      vectors, transmission, diagnosis, epidemiology, morbidity and treatment. It is
      concluded that there is an urgent need for more research on this widespread but
      greatly neglected infection in order to properly assess its public health
      significance and as a background for identifying and recommending optimal means
      and strategies for treatment and control.

PMID- 20152791
TI  - Development of a noncompetitive phage anti-immunocomplex assay for brominated
      diphenyl ether 47.
AB  - We present a new application of the noncompetitive phage anti-immunocomplex assay
      (PHAIA) by converting an existing competitive assay to a versatile noncompetitive
      sandwich-type format using immunocomplex binding phage-borne peptides to detect
      the brominated flame retardant, brominated diphenyl ether 47 (BDE 47). Three
      phage-displayed 9-mer disulfide-constrained peptides that recognize the BDE 47
      polyclonal antibody immunocomplex were isolated. The resulting PHAIAs showed
      variable sensitivities, and the most sensitive peptide had a dose-response curve
      with an SC(50) (concentration of analyte producing 50% saturation of the signal)
      of 0.7ng/ml BDE 47 and a linear range of 0.3-2ng/ml, which was nearly identical
      to the best heterologous competitive format (IC(50) of 1.8ng/ml, linear range of
      0.4-8.5/ml). However, the PHAIA was 1400-fold better than homologous competitive
      assay. The validation of the PHAIA with extracts of house furniture foam as well
      as human and calf sera spiked with BDE 47 showed overall recovery of 80-113%. The
      PHAIA was adapted to a dipstick format (limit of detection of 3.0ng/ml), and a
      blind test with six random extracts of local house furniture foams showed that
      the results of the PHAIA and dipstick assay were consistent, giving the same
      positive and negative detection.

PMID- 20152792
TI  - Identification of two antagonists of the scavenger receptor CD36 using a high
      throughput screening model.
AB  - CD36, a class B scavenger receptor, is an integral membrane protein that mediates
      the endocytosis of modified lipoproteins. The functions of CD36 are complex and
      have been associated with atherosclerosis. In the current study, we developed a
      high-throughput screening (HTS) assay to identify small molecule antagonists by
      expressing human CD36 using a Bac-to-Bac baculovirus expression system in
      Spodoptera frugiperda (Sf9) cells. Uptake of 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate-labeled acetylated low-density
      lipoprotein (DiI-AcLDL) revealed that the IC(50) values for the CD36 ligands
      oxidatively modified LDL (Ox-LDL), Ac-LDL, and high-density lipoprotein (HDL)
      were 0.039, 0.019, and 0.010 microg/ml, respectively. Using the HTS assay, two
      novel compounds, 2016481B and 2038751B, were found to inhibit DiI-AcLDL uptake in
      insect cells and exhibited IC(50) values of 17.4 and 23.7 microM, respectively.
      These two novel compounds also inhibited DiI-AcLDL uptake in cultured Chinese
      hamster ovary (CHO) cells permanently expressing human CD36. Furthermore, these
      two compounds inhibited lipid accumulation in RAW 264.7 murine macrophage cells
      in foam cell assays. This HTS assay represents a potential method for identifying
      more effective macrophage scavenger receptor antagonists, which may serve as
      starting points for the development of novel anti-atherosclerotic agents.

PMID- 20152793
TI  - Empirically optimized flow cytometric immunoassay validates ambient analyte
      theory.
AB  - Ekins' ambient analyte theory predicts, counterintuitively, that an immunoassay's
      limit of detection can be improved by reducing the amount of capture antibody. In
      addition, it also anticipates that results should be insensitive to the volume of
      sample as well as the amount of capture antibody added. The objective of this
      study was to empirically validate all of the performance characteristics
      predicted by Ekins' theory. Flow cytometric analysis was used to detect binding
      between a fluorescent ligand and capture microparticles because it can directly
      measure fractional occupancy, the primary response variable in ambient analyte
      theory. After experimentally determining ambient analyte conditions, comparisons
      were carried out between ambient and nonambient assays in terms of their signal
      strengths, limits of detection, and sensitivity to variations in reaction volume
      and number of particles. The critical number of binding sites required for an
      assay to be in the ambient analyte region was estimated to be 0.1 VK(d). As
      predicted, such assays exhibited superior signal/noise levels and limits of
      detection and were not affected by variations in sample volume and number of
      binding sites. When the signal detected measures fractional occupancy, ambient
      analyte theory is an excellent guide to developing assays with superior
      performance characteristics.

PMID- 20152794
TI  - Domain-level stability of an antibody monitored by reduction, differential
      alkylation, and mass spectrometry analysis.
AB  - Human immunoglobulin G1 (IgG1) contains 12 domains, and each has an intrachain
      disulfide bond that connects the two layers of antiparallel beta-sheets. These
      intrachain disulfide bonds are shielded from solvents under native conditions.
      Therefore, accessibility of the disulfide bonds to reduction under conditions
      that unfold antibody has the potential to be a good indicator of the
      thermodynamic stability of each domain. The stability of a recombinant monoclonal
      antibody at the domain level was investigated using a novel method involving
      reduction of the disulfide bonds in the presence of increasing amounts of
      guanidine hydrochloride and alkylation with [(12)C]iodoacetic acid, which was
      followed by reduction of the remaining disulfide bonds and alkylation with
      [(13)C]iodoacetic acid. The percentage of modification by [(12)C]iodoacetic acid
      of each cysteine residue was calculated using mass spectra of the cysteine
      containing tryptic peptides and used to follow the unfolding of each domain. It
      demonstrated that the CH2 domain was the least stable domain of the antibody,
      whereas the CH3 domain was the most stable domain of the antibody. Other domains
      showed intermediate resistance to the denaturant concentration, similar to the
      overall unfolding transition monitored by the intrinsic tryptophan fluorescence
      wavelength shift.

PMID- 20152795
TI  - Cell biology meets biophysics to unveil the different mechanisms of penetratin
      internalization in cells.
AB  - Although cell-penetrating peptides are widely used as molecular devices to cross
      membranes and transport molecules or nanoparticles inside cells, the underlying
      internalization mechanism for such behavior is still studied and discussed. One
      of the reasons for such a debate is the wide panel of chemically different cell
      penetrating peptides or cargo that is used. Indeed the intrinsic physico-chemical
      properties of CPP and conjugates strongly affect the cell membrane recognition
      and therefore the internalization pathways. Altogether, the mechanisms described
      so far should be shared between two general pathways: endocytosis and direct
      translocation. As it is established now that one cell-penetrating peptide can
      internalize at the same time by these two different pathways, the balance between
      the two pathways relies on the binding of the cell-penetrating peptide or
      conjugate to specific cell membrane components (carbohydrates, lipids). Like
      endocytosis which includes clathrin- and caveolae-dependent processes and
      macropinocytosis, different translocation mechanisms could co-exist, an idea that
      emerges from recent studies. In this review, we will focus solely on penetratin
      membrane interactions and internalization mechanisms.

PMID- 20152796
TI  - Use of bicistronic vectors in combination with flow cytometry to screen for
      effective small interfering RNA target sequences.
AB  - The efficacy and specificity of small interfering RNAs (siRNAs) are largely
      dependent on the siRNA sequence. Since only empirical strategies are currently
      available for predicting these parameters, simple and accurate methods for
      evaluating siRNAs are needed. To simplify such experiments, target genes are
      often tagged with reporters for easier readout. Here, we used a bicistronic
      vector expressing a target gene and green fluorescent protein (GFP) to create a
      system in which the effect of an siRNA sequence was reflected in the GFP
      expression level. Cells were transduced with the bicistronic vector, expression
      vectors for siRNA and red fluorescent protein (RFP). Flow cytometric analysis of
      the transduced cells revealed that siRNAs for the target gene silenced GFP from
      the bicistronic vector, but did not silence GFP transcribed without the target
      gene sequence. In addition, the mean fluorescence intensities of GFP on RFP
      expressing cells correlated well with the target gene mRNA and protein levels.
      These results suggest that this flow cytometry-based method enables us to
      quantitatively evaluate the efficacy and specificity of siRNAs. Because of its
      simplicity and effectiveness, this method will facilitate the screening of
      effective siRNA target sequences, even in high-throughput applications.

PMID- 20152797
TI  - Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size
      and decreases TSH-induced lipolysis.
AB  - BACKGROUND: The primary function of TSH is to activate TSH receptors (TSHr) in
      the thyroid gland and thereby stimulate thyroid hormone synthesis and secretion.
      TSHr are also expressed in other organs, but their physiological importance is
      still unclear. We have previously shown that TSHr, expressed in adipocytes, are
      of potential importance for lipolysis and extrauterine adaptation of the neonate.
      METHODOLOGY: To further study the role of TSHr in adipocytes we selectively
      removed the TSHr gene in mice adipocytes by using the Cre-loxP recombination
      system (B6.Cg-Tg (Fabp4-Cre) 1Rev/J. TSHr knockout (KO) newborn mice were
      phenotypically characterized. Isolated adipocytes from 8-week-old male mice were
      studied in term of adipocyte size and metabolism. RESULTS: Mice lacking TSHr in
      adipocytes were apparently normal at birth and no differences in thyroid gland
      function or histology were observed. Sensitivity to TSH-induced lipolysis was ten
      times lower in adipocytes from targeted animals compared to wild-type. This
      indicates that adipocytes from targeted animals are refractory to stimulation of
      physiological concentrations of TSH. Catecholamine-induced lipolysis and insulin
      induced inhibition of lipolysis were unaltered. Adipocyte size was increased in
      the targeted animals. Basal lipolysis was increased as an effect of the increased
      adipocyte size. CONCLUSION: Our results indicate that adipocyte TSHr under normal
      conditions affects adipocyte growth and development.

PMID- 20152798
TI  - IKKbeta specifically binds to P16 and phosphorylates Ser8 of P16.
AB  - In spite of its central roles in cell cycle progression, senescence, and aging,
      knowledge about the posttranslational regulation of P16 (also known as INK4A and
      MTS1) remains limited. While it has been reported that P16 could be
      phosphorylated at Ser7, Ser8, Ser140, and Ser152, the corresponding kinases have
      not been identified yet. Here we report that IKKbeta, a primary kinase for
      IkappaBalpha phosphorylation, is involved in P16 phosphorylation.
      Immunoprecipitation and kinase assays showed that IKKbeta specifically binds to
      P16 and phosphorylates P16 at Ser8 in WI38 cells. Biochemical characterization of
      phosphomimetic Ser-->Glu P16 mutants demonstrated that phosphorylation at Ser8 of
      P16 brings about a significant loss of its cyclin-dependent kinase (CDK) 4
      inhibitory activity while P16 retains structurally and functionally intact upon
      phosphorylation at Ser7, Ser140, and Ser152. Our results reveal the novel role of
      IKKbeta in P16 phosphorylation and broaden our understanding of the regulation of
      P16.

PMID- 20152799
TI  - One simple step in the identification of the cofactors signals, one giant leap
      for the solution structure determination of multiheme proteins.
AB  - Multiheme proteins play major roles in various biological systems. Structural
      information on these systems in solution is crucial to understand their
      functional mechanisms. However, the presence of numerous proton-containing groups
      in the heme cofactors and the magnetic properties of the heme iron, in particular
      in the oxidised state, complicates significantly the assignment of the NMR
      signals. Consequently, the multiheme proteins superfamily is extremely under
      represented in structural databases, which constitutes a severe bottleneck in the
      elucidation of their structural-functional relationships. In this work, we
      present a strategy that simplifies the assignment of the NMR signals in multiheme
      proteins and, concomitantly, their solution structure determination, using the
      triheme cytochrome PpcA from the bacterium Geobacter sulfurreducens as a model.
      Cost-effective isotopic labeling was used to double label (13C/15N) the protein
      in its polypeptide chain, with the correct folding and heme post-translational
      modifications. The combined analysis of 1H-13C HSQC NMR spectra obtained for
      labeled and unlabeled samples of PpcA allowed a straight discrimination between
      the heme cofactors and the polypeptide chain signals and their confident
      assignment. The results presented here will be the foundations to assist solution
      structure determination of multiheme proteins, which are still very scarce in the
      literature.

PMID- 20152800
TI  - Cleavage-induced termination in U2 snRNA gene expression.
AB  - The maturation of many small nuclear RNAs is dependent on RNase III-like
      endonuclease mediated cleavage, which generates a loading site for the exosome
      complex that trims the precursor at its 3' end. Using a temperature sensitive
      Pac1 nuclease, here we show that the endonuclease cleavage is equally important
      in terminating the transcription of the U2 snRNA in Schizosaccharomyces pombe.
      Using a temperature sensitive Dhp1p 5'-->3' exonuclease, we demonstrate that it
      also is an essential component of the termination pathway. Taken together the
      results support a "reversed torpedoes" model for the termination and maturation
      of the U2 snRNA; the Pac1 endonuclease cleavage provides entry sites for the 3'
      and 5' exonuclease activities, leading to RNA maturation in one direction and
      transcript termination in the other.

PMID- 20152801
TI  - Interaction of calcium with the human divalent metal-ion transporter-1.
AB  - Iron deficiency is the most prevalent micronutrient deficiency worldwide. Whereas
      dietary calcium is known to reduce the bioavailability of iron, the molecular
      basis of this interaction is not understood. We tested the hypothesis that
      divalent metal-ion transporter-1 (DMT1)-the principal or only mechanism by which
      nonheme iron is taken up at the intestinal brush border-is shared also by
      calcium. We expressed human DMT1 in RNA-injected Xenopus oocytes and examined its
      activity using radiotracer assays and the voltage clamp. DMT1 did not mediate
      45Ca2+ uptake. Instead, we found that Ca2+ blocked the Fe2+-evoked currents and
      inhibited 55Fe2+ uptake in a noncompetitive manner (K(i) approximately 20 mM).
      The mechanism of inhibition was independent of voltage and did not involve
      intracellular Ca2+ signaling. The alkaline-earth metal ions Ba2+, Sr2+, and Mg2+
      also inhibited DMT1-mediated iron-transport activity. We conclude that Ca2+ is a
      low-affinity noncompetitive inhibitor--but not a transported substrate--of DMT1,
      explaining in part the effect of high dietary calcium on iron bioavailability.

PMID- 20152802
TI  - NMR characterization of intramolecular interaction of osteopontin, an
      intrinsically disordered protein with cryptic integrin-binding motifs.
AB  - Osteopontin (OPN) is an integrin-binding protein found in a variety of tissues
      and physiological fluids and is involved in divergent biological processes such
      as migration, adhesion and signaling in integrin-independent as well as dependent
      manners. The adhesive activity of this protein is modulated upon cleavage by
      thrombin at the central part of the molecule, in the vicinity of the integrin
      binding sequences. Although detailed structural characterization is crucial for
      further understanding of the regulatory mechanisms of the OPN functions, its
      intrinsically disordered property hampers in-depth conformational analyses. Here
      we report an NMR study of mouse OPN and its N-terminal thrombin-cleavage product
      to characterize intramolecular interaction of this molecule. Paramagnetic
      relaxation enhancement experiment revealed that OPN exhibits a long-range
      intramolecular interaction between the N- and C-terminal regions. Furthermore,
      our NMR data showed that anti-OPN antibody OPN1.2, whose reactivity is impaired
      by deletion or amino acid substitutions of the arginine-aspartate-glycine
      integrin-binding motif, binds the N-terminal side of the integrin-binding motifs
      suggesting the existence of intramolecular interaction. These data suggest that
      functional interactions of OPN with integrins and the other binding partners can
      be modulated by the intramolecular interactions.

PMID- 20152803
TI  - Altered expression of sphingosine kinase 1 and sphingosine-1-phosphate receptor 1
      in mouse hippocampus after kainic acid treatment.
AB  - Kainic acid (KA) induces hippocampal cell death and astrocyte proliferation.
      There are reports that sphingosine kinase (SPHK)1 and sphingosine-1- phosphate
      (S1P) receptor 1 (S1P(1)) signaling axis controls astrocyte proliferation. Here
      we examined the temporal changes of SPHK1/S1P(1) in mouse hippocampus during KA
      induced hippocampal cell death. Mice were killed at 2, 6, 24, or 48 h after KA
      (30 mg/kg) injection. There was an increase in Fluoro-Jade B-positive cells in
      the hippocampus of KA-treated mice with temporal changes of glial fibrillary
      acidic protein (GFAP) expression. The lowest level of SPHK1 protein expression
      was found 2h after KA treatment. Six hours after KA treatment, the expression of
      SPHK1 and S1P(1) proteins steadily increased in the hippocampus. In
      immunohistochemical analysis, SPHK1 and S1P(1) are more immunoreactive in
      astrocytes within the hippocampus of KA-treated mice than in hippocampus of
      control mice. These results indicate that SPHK1/S1P(1) signaling axis may play an
      important role in astrocytes proliferation during KA-induced excitotoxicity.

PMID- 20152804
TI  - Brief exposure to carbon monoxide preconditions cardiomyogenic cells against
      apoptosis in ischemia-reperfusion.
AB  - We examined whether and how pretreatment with carbon monoxide (CO) prevents
      apoptosis of cardioblastic H9c2 cells in ischemia-reperfusion. Reperfusion (6 h)
      following brief ischemia (10 min) induced cytochrome c release, activation of
      caspase-9 and caspase-3, and apoptotic nuclear condensation. Brief CO
      pretreatment (10 min) or a caspase-9 inhibitor (Z-LEHD-FMK) attenuated these
      apoptotic changes. Ischemia-reperfusion increased phosphorylation of Akt at
      Ser472/473/474, and this was enhanced by CO pretreatment. A specific Akt
      inhibitor (API-2) blunted the anti-apoptotic effects of CO in reperfusion. In
      normoxic cells, CO enhanced O2(-) generation, which was inhibited by a
      mitochondrial complex III inhibitor (antimycin A) but not by a NADH oxidase
      inhibitor (apocynin). The CO-enhanced Akt phosphorylation was suppressed by an
      O2(-) scavenger (Tiron), catalase or a superoxide dismutase (SOD) inhibitor
      (DETC). These results suggest that CO pretreatment induces mitochondrial
      generation of O2(-), which is then converted by SOD to H2O2, and subsequent Akt
      activation by H2O2 attenuates apoptosis in ischemia-reperfusion.

PMID- 20152805
TI  - Presynaptic glycine receptors on hippocampal mossy fibers.
AB  - Presynaptic glycine receptors (GlyRs) have been implicated in the regulation of
      glutamatergic synaptic transmission. Here, we characterized presynaptic GlyR
      mediated currents by patch-clamp recording from mossy fiber boutons (MFBs) in rat
      hippocampal slices. In MFBs, focal puff-application of glycine-evoked chloride
      currents that were blocked by the GlyR antagonist strychnine. Their amplitudes
      declined substantially during postnatal development, from a mean conductance per
      MFB of approximately 600 pS in young to approximately 130 pS in adult animals.
      Single-channel analysis revealed multiple conductance states between
      approximately 20 and approximately 120 pS, consistent with expression of both
      homo- and hetero-oligomeric GlyRs. Accordingly, estimated GlyRs densities varied
      between 8-17 per young, and 1-3 per adult, MFB. Our results demonstrate that
      functional presynaptic GlyRs are present on hippocampal mossy fiber terminals and
      suggest a role of these receptors in the regulation of glutamate release during
      the development of the mossy fiber--CA3 synapse.

PMID- 20152806
TI  - Highly conserved sequences for human neutralization epitope on hemagglutinin of
      influenza A viruses H3N2, H1N1 and H5N1: Implication for human monoclonal
      antibody recognition.
AB  - The epitope sequences within the hemagglutinin (HA) of influenza A virus H3N2 at
      amino acid residues 173-181 and 227-239 that forms anti-parallel beta-sheet
      structure are similarly recognized by human monoclonal antibodies (HuMAbs), B-1
      and D-1 that we recently obtained using the peripheral blood lymphocytes from two
      influenza-vaccinated volunteers. Both HuMAbs showed strong global neutralization
      of H3N2 strains. Here we show the significant conservation of the beta-sheet
      region consisting of the above-mentioned two epitope regions in H3N2. In
      addition, we also identified the corresponding regions with similar structure in
      other subtypes such as H1N1 and H5N1. These two regions are similarly located
      underneath the receptor-binding sites of individual subtypes. Analysis of those
      regions using sequences available from the Influenza Virus Resource at the
      National Center for Biotechnology Information revealed that compared with those
      in the known neutralizing epitopes A-E, those sequences were fairly conserved in
      human H3N2 (n=7955), swine H1N1 (n=360) and swine H3N2 (n=235); and highly
      conserved in human H1N1 (n=2722), swine-origin pandemic H1N1 (n=1474), human H5N1
      (n=319) and avian H5N1 (n=2349). Phylogenetic tree for these regions formed
      clearly separable clusters for H1N1, H3N2 and H5N1, irrespective of different
      host origin. These data may suggest a possible significance of those regions for
      development of alternative vaccine that could induce neutralizing antibodies
      reactive against wide-range of influenza virus strains.

PMID- 20152807
TI  - Human adipose-derived stem cells enhance the glutamate uptake function of GLT1 in
      SOD1(G93A)-bearing astrocytes.
AB  - Impaired glutamate uptake function of astrocytes associated with accumulation of
      extracellular glutamate is a well-documented feature of amyotrophic lateral
      sclerosis (ALS). Enhancing the uptake function of astrocytic glutamate transport
      1 (GLT1) may be a potential treatment for this disease. Human adipose-derived
      stem cells (hADSCs) are capable of secreting a large number of cytokines which
      exhibit diverse pharmacological effects. Therefore, we investigate the influence
      of the soluble factors released by hADSCs on the GLT1 in primary astrocytes
      cultured from SOD1(G93A) mice, a widely studied mutant human SOD1 transgenic
      model of ALS. Our data indicate that soluble factors from hADSCs significantly
      upregulate the expression of GLT1 in SOD1(G93A)-bearing astrocytes, which result
      in enhanced glutamate uptake function. The upregulation of GLT1 is accompanied by
      the inhibition of caspase-3 activation in mutant astrocytes. In addition, we find
      that hADSCs cocultured with SOD1(G93A)-bearing astrocytes produce more VEGF, HGF
      and IGF-1, which are reported to have neuroprotective effects. Our results
      suggest that hADSCs may be a potential candidate in cellular therapy for ALS.

PMID- 20152808
TI  - An antiviral disulfide compound blocks interaction between arenavirus Z protein
      and cellular promyelocytic leukemia protein.
AB  - The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be
      redistributed by virus infection. In particular, lymphocytic choriomeningitis
      virus (LCMV) influences disruption of PML NB through the interaction of PML with
      the arenaviral Z protein. In a previous report, we have shown that the disulfide
      compound NSC20625 has antiviral and virucidal properties against arenaviruses,
      inducing unfolding and oligomerization of Z without affecting cellular RING
      containing proteins such as the PML. Here, we further studied the effect of the
      zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells
      infected with LCMV or transiently transfected with Z protein constructs,
      treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic
      pattern to punctate, discrete NB which appeared identical to NB found in control,
      uninfected cells. Similar results were obtained in cells transfected with a
      construct expressing a Z mutant in zinc-binding site 2 of the RING domain,
      confirming that this Z-PML interaction requires the integrity of only one zinc
      binding site. Altogether, these results show that the compound NSC20625
      suppressed Z-mediated PML NB disruption and may be used as a tool for designing
      novel antiviral strategies against arenavirus infection.

PMID- 20152809
TI  - PI3K/Akt/mTOR signaling regulates glutamate transporter 1 in astrocytes.
AB  - Reduction in or dysfunction of glutamate transporter 1 (GLT1) is linked to
      several neuronal disorders such as stroke, Alzheimer's disease, and amyotrophic
      lateral sclerosis. However, the detailed mechanism underlying GLT1 regulation has
      not been fully elucidated. In the present study, we first demonstrated the
      effects of mammalian target of rapamycin (mTOR) signaling on GLT1 regulation. We
      prepared astrocytes cultured in astrocyte-defined medium (ADM), which contains
      several growth factors including epidermal growth factor (EGF) and insulin. The
      levels of phosphorylated Akt (Ser473) and mTOR (Ser2448) increased, and GLT1
      levels were increased in ADM-cultured astrocytes. Treatment with a
      phosphatidylinositol 3-kinase (PI3K) inhibitor or an Akt inhibitor suppressed the
      phosphorylation of Akt (Ser473) and mTOR (Ser2448) as well as decreased ADM
      induced GLT1 upregulation. Treatment with the mTOR inhibitor rapamycin decreased
      GLT1 protein and mRNA levels. In contrast, rapamycin did not affect Akt (Ser473)
      phosphorylation. Our results suggest that mTOR is a downstream target of the
      PI3K/Akt pathway regulating GLT1 expression.

PMID- 20152810
TI  - Targeting of renal proximal tubule Na,K-ATPase by salt-inducible kinase.
AB  - The renal proximal tubule (RPT) is a central locale for Na+ reabsorption, and
      blood pressure regulation. Na+ reabsorption in the RPT depends upon the Na,K
      ATPase, which is controlled by a complex regulatory network, including Salt
      Inducible Protein Kinase (SIK). SIKs are recently discovered members of the AMP
      activated Protein Kinase (AMPK) family, which regulate salt homeostasis and
      metabolism in a number of tissues. In the RPT, SIK interacts with the Na,K-ATPase
      in the basolateral membrane (BM), regulating both the activity and level of Na,K
      ATPase in the BM. Thus, Na,K-ATPase activity can be rapidly adjusted in response
      to changes in Na+ balance. Long-term changes in Na+ intake affect the state of
      SIK phosphorylation, and as a consequence the phosphorylation of TORCs,
      Transducers of Regulated CREB (cAMP Regulatory Element Binding Protein). Once
      phosphorylated, TORCs enter the nucleus, and activate transcription of the ATP1B1
      gene encoding for the Na,K-ATPase beta subunit.

PMID- 20152811
TI  - A strategy for the production of soluble human senescence marker protein-30 in
      Escherichia coli.
AB  - Senescence marker protein-30 (SMP30) has been reported to hydrolyze diisopropyl
      fluorophosphate (DFP), a surrogate compound of chemical warfare nerve agents.
      Thus, SMP30 has the potential to be useful as a prophylactic against chemical
      warfare nerve agent toxicity. Our efforts to generate human SMP30 in bacteria
      using a variety of expression vectors invariably resulted in insoluble and
      inactive preparations. In this study, properly folded and active recombinant
      human SMP30 (rHuSMP30) was produced in Escherichia coli by coexpressing it with
      molecular chaperones in a combined strategy. The coexpression of rHuSMP30 with
      GroES/GroEL/Tf at 15 degrees C, combined with the addition of a membrane
      fluidizer, increased osmolytes, and a two-step expression resulted in the highest
      enhancement of solubility and DFPase activity. Our results pave the way for
      exploring the use of rHuSMP30 against organophosphate and nerve agent toxicity.

PMID- 20152812
TI  - Antihypertrophic effects of adiponectin on cardiomyocytes are associated with the
      inhibition of heparin-binding epidermal growth factor signaling.
AB  - This study was aimed to investigate whether the antihypertrophic effects of
      adiponectin in murine hearts are associated with the modulation of HB-EGF
      signaling. We determined the myocardial expressions of adiponectin and
      adiponectin receptors, brain natriuretic peptide (BNP), and HB-EGF in normal and
      hypertrophied hearts of adiponectin knockout mice or wild-type mice with
      transverse aortic constriction (TAC). Then, we observed the effects of
      adiponectin on cardiac hypertrophy and HB-EGF signaling in cultured neonatal rat
      cardiomyocytes and whole hearts of adiponectin-null mice. The myocardial mRNA and
      protein expressions of adiponectin in the hypertrophied hearts were significantly
      downregulated, and the mRNA expression of adiponectin was inversely correlated
      with the heart-to-body weight ratio, BNP, and HB-EGF. The TAC-induced cardiac
      hypertrophy and EGF receptor (EGFR) activation in the adiponectin knockout mice
      were significantly greater than those in the wild-type mice. Furthermore, in
      vitro experiments revealed that adiponectin inhibited HB-EGF-stimulated protein
      synthesis, HB-EGF shedding, and EGFR phosphorylation. We conclude that the
      inhibition of HB-EGF mediated EGFR activation is one of the alternative
      mechanisms for the antihypertrophic action of adiponectin.

PMID- 20152813
TI  - In vitro and in vivo interaction of AtRma2 E3 ubiquitin ligase and auxin binding
      protein 1.
AB  - E3 ubiquitin (Ub) ligases play diverse roles in cellular regulation in
      eukaryotes. Three homologous AtRmas (AtRma1, AtRma2, and AtRma3) were recently
      identified as ER-localized Arabidopsis homologs of human RING membrane-anchor E3
      Ub ligase. Here, auxin binding protein 1 (ABP1), one of the auxin receptors in
      Arabidopsis, was identified as a potential substrate of AtRma2 through a yeast
      two-hybrid assay. An in vitro pull-down assay confirmed the interaction of full
      length AtRma2 with ABP1. AtRma2 was transiently expressed in tobacco (Nicotiana
      benthamiana) plants through an Agrobacterium-mediated infiltration method and
      bound ABP1 in vivo. In vitro ubiquitination assays revealed that bacterially
      expressed AtRma2 ubiquitinated ABP1. ABP1 was poly-ubiquitinated in tobacco cells
      and its stability was significantly increased in the presence of MG132, a 26S
      proteasome inhibitor. This suggests that ABP1 is controlled by the Ub/26S
      proteasome system. Therefore, AtRma2 is likely involved in the cellular
      regulation of ABP1 expression levels.

PMID- 20152814
TI  - Induced epigenetic modifications of the promoter chromatin silence survivin and
      inhibit tumor growth.
AB  - Anti-apoptotic survivin is over-expressed in a variety of human carcinomas and is
      considered as a therapeutic target in cancers. Suppression of survivin mRNA by
      RNAi and anti-sense nucleotides has proved to be a powerful anti-tumor therapy in
      both animal models and human investigations. In this communication, we tested an
      alternative approach to silence survivin by knocking down its gene transcription
      through a short methylated oligonucleotide (SurKex) that is complementary to the
      survivin gene promoter. Treatment of NCI-H460 cells with SurKex significantly
      suppressed the production of survivin mRNA and its oncoprotein. DNA bisulfite
      sequencing showed that SurKex induced site-specific de novo CpG methylation in
      the complementary region of survivin promoter. Chromatin immunoprecipitation
      assay also demonstrated that SurKex induced histone hypermethylation at histone
      H3K9 and H3K27 as well as deacetylation of histone H4 in the same regulatory
      region. SurKex remarkably inhibited tumor growth in nude mice bearing xenograft
      tumors. This study demonstrates that the synthetic methylated oligonucleotide
      SurKex inhibits tumor growth by silencing the survivin gene using a mechanism of
      altering the epigenotype in the survivin promoter. Thus, targeted epigenetic
      modification in the gene promoter may offer a new general strategy to silence
      tumor-related genes in tumor therapy.

PMID- 20152815
TI  - Transitional change in rat fetal cell proliferation in response to ghrelin and
      des-acyl ghrelin during the last stage of pregnancy.
AB  - Expression of mRNA for the ghrelin receptor, GHS-R1a, was detected in various
      peripheral and central tissues of fetal rats, including skin, bone, heart, liver,
      gut, brain and spinal cord, on embryonic day (ED)15 and ED17. However, its
      expression in skin, bone, heart and liver, but not in gut, brain and spinal cord,
      became relatively weak on ED19 and disappeared after birth (ND2). Ghrelin and des
      acyl ghrelin facilitated the proliferation of cultured fetal (ED17, 19), but not
      neonatal (ND2), skin cells. On the other hand, with regard to cells from the
      spinal cord and hypothalamus, the proliferative effect of ghrelin continued after
      birth, whereas the effect of des-acyl ghrelin on neurogenesis in these tissues
      was lost at the ED19 fetal and ND2 neonatal stages. Immunohistochemistry revealed
      that the cells in the hypothalamus induced to proliferate by ghrelin at the ND2
      stage were positive for nestin and glial fibrillary acidic protein. These results
      suggest that in the period immediately prior to, and after birth, rat fetal cells
      showing proliferation in response to ghrelin and des-acyl ghrelin are at a
      transitional stage characterized by alteration of the expression of GHS-R1a and
      an undefined des-acyl ghrelin receptor, their responsiveness varying among
      different tissues.

PMID- 20152816
TI  - PKC-delta induces cardiomyogenic gene expression in human adipose-derived stem
      cells.
AB  - Stromal cells from fat tissues exhibit properties of mesenchymal stem cells from
      other sources with the ability to differentiate towards multiple cell types.
      However, effective differentiation of these mesenchymal cells, called adipose
      derived stem cells (ADSCs), towards cardiomyogenic lineage has been limited to a
      small number of isolated clones in an extended culture. Previously, we reported
      that treatment with phorbol ester induces the expression of several
      cardiomyogenic genes in the absence of serum. This study was performed to
      identify the roles of PKC isoforms in cardiomyogenic gene expression of ADSCs.
      Treatment with 10nM phorbol myristate acetate (PMA) for 24h caused sustained
      increases in mRNA levels for various cardiomyogenic genes, such as Mef2C, cardiac
      actin and troponin, for at least 6 days following the drug removal. The use of
      various inhibitors specific for PKC isoforms demonstrated that the novel PKC
      theta/delta isoforms mediate the PMA effects. RT-PCR revealed that ADSCs express
      significant mRNA for PKC-delta, but not theta isoform. Overexpression of cDNA for
      PKC-delta resulted in marked increases in cardiac mRNA expression. These results
      indicate that activation of PKC-delta induces the expression of multiple
      cardiomyogenic genes in ADSCs.

PMID- 20152817
TI  - Differential regulation of GPR54 transcription by specificity protein-1 and
      partial estrogen response element in mouse pituitary cells.
AB  - Precise spatial and temporal expression of the recently identified G-protein
      coupled receptor GPR54 is critical for proper reproductive function and
      metastasis suppression. However, regulatory factors that control GPR54 expression
      remain unknown. Thus, the identification of these cis-acting DNA elements can
      provide insight into the role of GPR54 in reproduction and cancer. Using
      luciferase reporter, electrophoretic mobility shift, and chromatin
      immunoprecipitation assays, we demonstrate that three SP1 sites and a partial
      estrogen response element modulate mouse GPR54 (mGPR54) promoter activity.
      Supporting experiments show transcription factor SP1 binds directly to the mGPR54
      promoter region and activates gene expression. In conclusion, these novel
      findings now identify factors that regulate activity of the mGPR54 promoter, and
      these factors are highly conserved across multiple mammalian species.

PMID- 20152818
TI  - Influence of polymorphism in dendritic cell-specific intercellular adhesion
      molecule-3-grabbing nonintegrin-related (DC-SIGNR) gene on HIV-1 trans-infection.
AB  - The dendritic cell-specific intercellular adhesion molecule-3-grabbing
      nonintegrin (DC-SIGN) and DC-SIGN-related (DC-SIGNR) molecules on the cell
      surface are known to enhance human immunodeficiency virus type 1 (HIV-1)
      infection by capturing the virions and transmitting them to CD4+ T-cell, a
      process termed trans-infection. The neck region and carbohydrate recognition
      domain of the two proteins are important for efficient binding to the HIV-1
      envelope protein. DC-SIGNR is polymorphic in Exons 4 and 5 that encode the neck
      region and carbohydrate recognition domain, respectively; the former contains a
      variable number of tandem repeats, and the latter the SNP (rs2277998). Since it
      remains unclear whether the DC-SIGNR polymorphism is related to the risk of HIV-1
      infection, we tested possible effects of the polymorphism on HIV-1 trans
      infection efficiency, by constructing six kinds of cDNAs encoding DC-SIGNR
      variants with various numbers of repeat units and various SNP. We were able to
      express the variants on the surface of Raji cells, a human B cell line. Flow
      cytometry showed that all the tested DC-SIGNR molecules were efficiently
      expressed on the cell surface at various levels; the assay for HIV trans
      infection efficacy showed that all the tested variants had that activity with
      different efficacy levels. We found a correlation between the HIV trans-infection
      efficiency and the mean fluorescent intensity of DC-SIGNR expression (R(2)=0.95).
      Thus, our results suggest that the variation of the tested DC-SIGNR genotypes
      affects the efficacy of trans-infection by affecting the amounts of the protein
      expressed on the cell surface.

PMID- 20152819
TI  - Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via
      inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms.
AB  - Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has
      recently been shown to possess antitumor activity in various cancer cells.
      However, the effects of DHA in preventing the invasion of cancer cells have not
      been studied. In the present study, we investigated the inhibitory effects of DHA
      on tumor invasion and migration and the possible mechanisms involved using human
      fibrosarcoma HT-1080 cells. DHA reduced PMA-induced activation of MMP-9 and MMP-2
      and further inhibited cell invasion and migration. DHA suppressed PMA-enhanced
      expression of MMP-9 protein, mRNA, and transcriptional activity through
      suppressing NF-kappaB and AP-1 activation without changing the level of tissue
      inhibitor of metalloproteinase (TIMP)-1. DHA also reduced PMA-enhanced MMP-2
      expression by suppressing membrane-type 1 MMP (MT1-MMP), but did not alter TIMP-2
      levels. DHA-inhibited PMA-induced NF-kappaB and c-Jun nuclear translocation,
      which are upstream of PMA-induced MMP-9 expression and invasion. Furthermore, DHA
      strongly repressed the PMA-induced phosphorylation of Raf/ERK and JNK, which are
      dependent on the PKCalpha pathway. In conclusion, we demonstrated that the anti
      invasive effects of DHA may occur through inhibition of PKCalpha/Raf/ERK and JNK
      phosphorylation and reduction of NF-kappaB and AP-1 activation, leading to down
      regulation of MMP-9 expression. The data presented show that DHA is an effective
      anti-metastatic agent that functions by down-regulating MMP-9 gene expression.

PMID- 20152820
TI  - The ghrelin gene allele 51Q (rs34911341) is a protective factor against the
      development of gestational diabetes.

PMID- 20152821
TI  - Simultaneous genotyping of microsatellite variations in HMOX1 and UGT1A1 genes
      using multicolored capillary electrophoresis.
AB  - OBJECTIVES: Our aim was to establish a reliable, rapid, and inexpensive method
      for the simultaneous genotyping of the HMOX-1 (heme oxygenase-1) and UGT1A1
      (bilirubin UDP-glucuronosyltransferase) gene promoter variations. RESULTS: The
      HMOX1 (GT)(n) and UGT1A1 (TA)(n) gene promoter variations were determined by
      fragment analysis using a single duplex PCR, with different fluorescent dye
      labeled primers; followed by multicolored capillary electrophoresis. CONCLUSION:
      This novel method provides simultaneous genotyping of key tandem repeat
      variations in the HMOX1 and UGT1A1 promoters.

PMID- 20152822
TI  - Evaluations of bioantioxidants in cryopreservation of umbilical cord blood using
      natural cryoprotectants and low concentrations of dimethylsulfoxide.
AB  - Transplantation using hematopoietic stem cells from umbilical cord blood (UCB) is
      a life-saving treatment option for patients with select oncologic diseases,
      immunologic diseases, bone marrow failure, and others. Often this transplant
      modality requires cryopreservation and storage of hematopoietic stem cells (HSC),
      which need to remain cryopreserved in UCB banks for possible future use. The most
      widely used cryoprotectant is dimethylsulfoxide (Me(2)SO), but at 37 degrees C,
      it is toxic to cells and for patients, infusion of cryopreserved HSC with Me(2)SO
      has been associated with side effects. Freezing of cells leads to chemical change
      of cellular components, which results in physical disruption. Reactive oxygen
      species (ROS) generation also has been implicated as cause of damage to cells
      during freezing. We assessed the ability of two bioantioxidants and two
      disaccharides, to enhance the cryopreservation of UCB. UCB was processed and
      subjected to cryopreservation in solutions containing different concentrations of
      Me(2)SO, bioantioxidants and disaccharides. Samples were thawed, and then
      analysed by: flow cytometry analysis, CFU assay and MTT viability assay. In this
      study, our analyses showed that antioxidants, principally catalase, performed
      greater preservation of: CD34+ cells, CD123+ cells, colony-forming units and cell
      viability, all post-thawed, compared with the standard solution of
      cryopreservation. Our present studies show that the addition of catalase improved
      the cryopreservation outcome. Catalase may act on reducing levels of ROS, further
      indicating that accumulation of free radicals indeed leads to death in
      cryopreserved hematopoietic cells.

PMID- 20152823
TI  - Reversible mitochondrial uncoupling in the cold phase during liver
      preservation/reperfusion reduces oxidative injury in the rat model.
AB  - Reversible uncoupling of the mitochondrial electron-transport chain may be one
      strategy to prevent intracellular oxidative stress during liver cold
      preservation/warm reperfusion (CP/WR) injury. 2,4-Dinitrophenol (DNP) is a potent
      water-soluble uncoupling agent for supplementation of the hepatic CP solution.
      The aim of this work was to investigate the possible influence of DNP in the CP
      solution on the isolated rat liver state during CP/WR. Livers were subjected to
      CP at 4 degrees C in sucrose-phosphate based solution (SPS) for 18 h, followed by
      WR for 60 min in vitro. The final concentration of DNP was 100 microM. DNP
      presence during the CP stage led to partial ATP level decrease accompanied by a
      significant diminution in liver TBARS and a prevention of antioxidant enzyme
      activity decrease (catalase, GSH-PO, GSH-Red) when compared with livers stored
      without DNP. After DNP wash-out during WR, an improvement in the mitochondrial
      functional state (higher respiratory control indices and ATP levels, and a
      decrease in V(4) respiration rates) were observed. This was concurrent with lower
      TBARS levels, higher antioxidant enzyme activities and significant increase of
      bile production. The results suggest that reversible uncoupling may be one way to
      influence oxidative stress associated with hepatic cold preservation.

PMID- 20152824
TI  - The experimental study for efficacy and safety of pancreatic cryosurgery.
AB  - OBJECTIVE: This study was designed to basic information concerning the efficacy
      and safety of cryosurgery for pancreatic cancer. Fifteen healthy pigs were used
      to perform biochemical analysis and histological assessment. METHODS: Following
      anesthesia and laparotomy, an argon-helium cryoprobe was inserted into the
      pancreas. The introduction of argon gas induced a rapid decrease in temperature
      to -160 degrees C (Group I, 5 pigs) or -110 degrees C (Group II, 5 pigs),
      respectively, resulting in ice-ball formation of 15-20mm diameter after 5 min.
      Following freezing, helium gas was circulated in the probe tip to increase the
      temperature to 10-20 degrees C over 3 min to thaw. The freeze/thaw cycle was then
      repeated. Group III (3 pigs) had a cryoprobe inserted, but without freezing, and
      Group IV (2 pigs) included untreated or normal control animals. Levels of serum
      amylase (AMY), IL-6 and C-RP were measured prior to freezing and for 7 days
      following the procedure. All pigs were euthanized 7 days post-treatment and
      pancreases were examined histologically. RESULTS: Neither hyperaemia, edema or
      hemorrhage were observed in the un-frozen parts of the pancreas. Histological
      assessment revealed a significant level of necrosis in the central and lateral
      regions of the tissue frozen within the ice-ball. All cellular ultrastructure was
      destroyed and only observable as a few of remaining nuclei with broken crests and
      degranulated mitochondria and rough endoplasmic reticulum. There was a
      significant increase of serum AMY levels for a brief period in both "deep frozen"
      and the "shallow frozen" groups. However, the AMY also increased in two pigs in
      the "normal control" group and one pig from the "inserted cryoprobe without
      freeze" control group. All experimental pigs appeared healthy until the sacrifice
      time. CONCLUSION: Cryosurgery is a safe and effective ablative procedure for
      pancreatic tissue resulting in minimal complications.

PMID- 20152825
TI  - Tenectin is a novel alphaPS2betaPS integrin ligand required for wing
      morphogenesis and male genital looping in Drosophila.
AB  - Morphogenesis of the adult structures of holometabolous insects is regulated by
      ecdysteroids and juvenile hormones and involves cell-cell interactions mediated
      in part by the cell surface integrin receptors and their extracellular matrix
      (ECM) ligands. These adhesion molecules and their regulation by hormones are not
      well characterized. We describe the gene structure of a newly described ECM
      molecule, tenectin, and demonstrate that it is a hormonally regulated ECM protein
      required for proper morphogenesis of the adult wing and male genitalia.
      Tenectin's function as a new ligand of the PS2 integrins is demonstrated by both
      genetic interactions in the fly and by cell spreading and cell adhesion assays in
      cultured cells. Its interaction with the PS2 integrins is dependent on RGD and
      RGD-like motifs. Tenectin's function in looping morphogenesis in the development
      of the male genitalia led to experiments that demonstrate a role for PS integrins
      in the execution of left-right asymmetry.

PMID- 20152826
TI  - Bazooka regulates microtubule organization and spatial restriction of germ plasm
      assembly in the Drosophila oocyte.
AB  - Localization of the germ plasm to the posterior of the Drosophila oocyte is
      required for anteroposterior patterning and germ cell development during
      embryogenesis. While mechanisms governing the localization of individual germ
      plasm components have been elucidated, the process by which germ plasm assembly
      is restricted to the posterior pole is poorly understood. In this study, we
      identify a novel allele of bazooka (baz), the Drosophila homolog of Par-3, which
      has allowed the analysis of baz function throughout oogenesis. We demonstrate
      that baz is required for spatial restriction of the germ plasm and axis
      patterning, and we uncover multiple requirements for baz in regulating the
      organization of the oocyte microtubule cytoskeleton. Our results suggest that
      distinct cortical domains established by Par proteins polarize the oocyte through
      differential effects on microtubule organization. We further show that
      microtubule plus-end enrichment is sufficient to drive germ plasm assembly even
      at a distance from the oocyte cortex, suggesting that control of microtubule
      organization is critical not only for the localization of germ plasm components
      to the posterior of the oocyte but also for the restriction of germ plasm
      assembly to the posterior pole.

PMID- 20152827
TI  - Emx2 and early hair cell development in the mouse inner ear.
AB  - Emx2 is a homeodomain protein that plays a critical role in inner ear
      development. Homozygous null mice die at birth with a range of defects in the
      CNS, renal system and skeleton. The cochlea is shorter than normal with about 60%
      fewer auditory hair cells. It appears to lack outer hair cells and some
      supporting cells are either absent or fail to differentiate. Many of the hair
      cells differentiate in pairs and although their hair bundles develop normally
      their planar cell polarity is compromised. Measurements of cell polarity suggest
      that classic planar cell polarity molecules are not directly influenced by Emx2
      and that polarity is compromised by developmental defects in the sensory
      precursor population or by defects in epithelial cues for cell alignment. Planar
      cell polarity is normal in the vestibular epithelia although polarity reversal
      across the striola is absent in both the utricular and saccular maculae. In
      contrast, cochlear hair cell polarity is disorganized. The expression domain for
      Bmp4 is expanded and Fgfr1 and Prox1 are expressed in fewer cells in the cochlear
      sensory epithelium of Emx2 null mice. We conclude that Emx2 regulates early
      developmental events that balance cell proliferation and differentiation in the
      sensory precursor population.

PMID- 20152828
TI  - The essential requirement for Runx1 in the development of the sternum.
AB  - Runx1 is highly expressed in chondroprogenitor and osteoprogenitor cells and in
      vitro experiments suggest that Runx1 is important in the early stages of
      osteoblast and chondrocyte differentiation. However, because Runx1 knockout mice
      are early embryonic lethal due to failure of hematopoiesis, the role of Runx1 in
      skeletogenesis remains unclear. We studied the role of Runx1 in skeletal
      development using a Runx1 reversible knockout mouse model. By crossing with Tie2
      Cre deletor mice, Runx1 expression was selectively rescued in the endothelial and
      hematopoietic systems but not in the skeleton. Although Runx1(Re/Re) embryos
      survived until birth and had a generally normal skeleton, the development of
      mineralization in the sternum and some skull elements was significantly
      disrupted. In contrast to wild-type embryos, the sternum of E17.5 Runx1(Re/Re)
      embryos showed high levels of Sox-9 and collagen type II expression and lack of
      development of hypertrophic chondrocytes. In situ hybridization analysis
      demonstrated that, in contrast to the vertebrae and long bones, the sternum of
      wild-type embryos expresses high levels of Runx1, but not Runx2, the master
      regulator of skeletogenesis. Thus, although Runx1 is not essential for major
      skeletal development, it does play an essential role in the development of the
      sternum and some skull elements.

PMID- 20152830
TI  - Pleiotropic effects of ezetimibe: do they really exist?
AB  - Ezetimibe represents a new lipid lowering agent which inhibits cholesterol
      absorption. It effectively reduces low-density lipoprotein cholesterol when
      administered either alone or in combination with statins. However, its effect on
      cardiovascular mortality remains under question since it failed to demonstrate
      any significant changes in the primary endpoints of the recently published
      ENHANCE and SEAS studies. A possible explanation for this unsuccessful outcome is
      that ezetimibe lacks pleiotropic effects. This article aims to review the
      potential pleiotropic effects of the drug mainly on inflammation markers,
      lipoprotein subfractions and endothelial function.

PMID- 20152829
TI  - Midline signaling regulates kidney positioning but not nephrogenesis through Shh.
AB  - The role of axial structures, especially the notochord, in metanephric kidney
      development has not been directly examined. Here, we showed that disruption of
      the notochord and floor plate by diphtheria toxin (DTA)-mediated cell ablation
      did not disrupt nephrogenesis, but resulted in kidney fusions, resembling
      horseshoe kidneys in humans. Axial disruptions led to more medially positioned
      metanephric mesenchyme (MM) in midgestation. However, neither axial disruption
      nor the ensuing positional shift of the MM affected the formation of nephrons and
      other structures within the kidney. Response to Shh signaling was greatly reduced
      in midline cell populations in the mutants. To further ascertain the molecular
      mechanism underlying these abnormalities, we specifically inactivated Shh in the
      notochord and floor plate. We found that depleting the axial source of Shh was
      sufficient to cause kidney fusion, even in the presence of the notochord. These
      results suggested that the notochord is dispensable for nephrogenesis but
      required for the correct positioning of the metanephric kidney. Axial Shh signal
      appears to be critical in conferring the effects of axial structures on kidney
      positioning along the mediolateral axis. These studies also provide insights into
      the pathogenesis of horseshoe kidneys and how congenital kidney defects can be
      caused by signals outside the renal primordia.

PMID- 20152831
TI  - The flavonoid dioclein reduces the production of pro-inflammatory mediators in
      vitro by inhibiting PDE4 activity and scavenging reactive oxygen species.
AB  - Reactive oxygen species, cytokines and chemokines produced at inflammatory sites
      are pivotal events in the progression of many diseases. Flavonoids are well-known
      for their antioxidant and anti-inflammatory activities. Here, we investigated the
      effects of the flavonoid dioclein on the production of mediators of inflammation
      in vitro and possible underlying mechanisms. Murine macrophages were pretreated
      with dioclein, rolipram, a PDE4 (cyclic nucleotide phosphosdiesterase type 4)
      inhibitor, or butylated hydroxytoluene (BHT), an antioxidant, and then activated
      with LPS or LPS/IFN-gamma. The concentration of TNF-alpha, IL-6, CXCL1/KC,
      CCL2/JE, and nitric oxide (NO) was determined on culture supernatants. To
      evaluate potential mechanisms of action, dioclein was tested for inhibition of
      PDE4 activity and for antioxidant properties by chemiluminescence assays.
      Dioclein was efficient in reducing the production of cytokines, chemokines and NO
      in a concentration-dependent manner (from 5 to 50muM). Dioclein was more
      effective than BHT and rolipram, while having similar inhibitory effects to the
      combination of BHT plus rolipram. Dioclein inhibited PDE4 activity with an
      approximate IC(50) of 16.8+/-1.4muM and strongly reduced the concentration of
      reactive oxygen species in cell and cell-free systems, being more effective than
      the standard antioxidant BHT. The flavonoid dioclein possesses significant
      antioxidant and PDE4 inhibitory activity, showing that the substance may have
      substantial advantages over mechanisms of action already described for many
      flavonoids. Such effects account for the anti-inflammatory effects of dioclein,
      mainly by reducing the concentration of mediators of inflammation, such as
      cytokines, chemokines and reactive oxygen species by macrophages.

PMID- 20152833
TI  - Heat shock factor 1 binds to and transcribes satellite II and III sequences at
      several pericentromeric regions in heat-shocked cells.
AB  - Cells respond to stress by activating the synthesis of heat shock proteins (HSPs)
      which protect the cells against the deleterious effects of stress. This mechanism
      is controlled by the heat shock factor 1 (HSF1). In parallel to HSP gene
      transcription, in human cells, HSF1 also binds to and transcribes satellite III
      repeated sequences present in numerous copies in the 9q12 pericentromeric region
      of chromosome 9. These HSF1 accumulation sites are termed nuclear stress bodies
      (nSBs). In tumor cells, however, the number of nSBs is higher than the number of
      9q12 copies, suggesting the existence of other HSF1 targets. In this paper, we
      were interested in characterizing these other HSF1 binding sites. We show that
      HSF1 indeed binds to the pericentromeric region of 14 chromosomes, thereby
      directing the formation of 'secondary nSBs'. The appearance of secondary nSBs
      depends on the number of satellite sequences present in the target locus, and on
      the cellular amount of HSF1 protein. Moreover, secondary nSBs also correspond to
      transcription sites, thus demonstrating that heat shock induces a genome-wide
      transcription of satellite sequences. Finally, by analyzing published
      transcriptomic data, we show that the derepression of these large heterochromatic
      blocks does not significantly affect the transcription of neighboring genes.

PMID- 20152832
TI  - Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse
      cortical neurons.
AB  - The adipocytokine apelin and its G protein-coupled APJ receptor were initially
      isolated from a bovine stomach and have been detected in the brain and
      cardiovascular system. Recent studies suggest that apelin can protect
      cardiomyocytes from ischemic injury. Here, we investigated the effect of apelin
      on apoptosis in mouse primary cultures of cortical neurons. Exposure of the
      cortical cultures to a serum-free medium for 24 h induced nuclear fragmentation
      and apoptotic death; apelin-13 (1.0-5.0 nM) markedly prevented the neuronal
      apoptosis. Apelin neuroprotective effects were mediated by multiple mechanisms.
      Apelin-13 reduced serum deprivation (SD)-induced ROS generation, mitochondria
      depolarization, cytochrome c release and activation of caspase-3. Apelin-13
      prevented SD-induced changes in phosphorylation status of Akt and ERK1/2. In
      addition, apelin-13 attenuated NMDA-induced intracellular Ca(2+) accumulation.
      These results indicate that apelin is an endogenous neuroprotective adipocytokine
      that may block apoptosis and excitotoxic death via cellular and molecular
      mechanisms. It is suggested that apelins may be further explored as a potential
      neuroprotective reagent for ischemia-induced brain damage.

PMID- 20152834
TI  - Pax6a and Pax6b are required at different points in neuronal progenitor cell
      proliferation during zebrafish photoreceptor regeneration.
AB  - The light-damaged zebrafish retina results in the death of photoreceptor cells
      and the subsequent regeneration of the missing rod and cone cells. Photoreceptor
      regeneration initiates with asymmetric Muller glial cell division to produce
      neuronal progenitor cells, which amplify, migrate to the outer nuclear layer
      (ONL), and differentiate into both classes of photoreceptor cells. In this study,
      we examined the role of the Pax6 protein in regeneration. In zebrafish, there are
      two Pax6 proteins, one encoded by the pax6a gene and the other encoded by the
      pax6b gene. We intravitreally injected and electroporated morpholinos that were
      complementary to either the pax6a or pax6b mRNA to knockdown the translation of
      the corresponding protein. Loss of Pax6b expression did not affect Muller glial
      cell division, but blocked the subsequent first cell division of the neuronal
      progenitors. In contrast, the paralogous Pax6a protein was required for later
      neuronal progenitor cell divisions, which maximized the number of neuronal
      progenitors. Without neuronal progenitor cell amplification, proliferation of
      resident ONL rod precursor cells, which can only regenerate rods, increased
      inversely proportional to the number of INL neuronal progenitor cells. This
      confirmed that Muller glial-derived neuronal progenitor cells are necessary to
      regenerate cones and that distinct mechanisms selectively regenerate rod and cone
      photoreceptors. This work also defines distinct roles for Pax6a and Pax6b in
      regulating neuronal progenitor cell proliferation in the adult zebrafish retina
      and increases our understanding of the molecular pathways required for
      photoreceptor cell regeneration.

PMID- 20152835
TI  - Glucocorticosteroids increase cell entry by hepatitis C virus.
AB  - BACKGROUND & AIMS: Corticosteroids are used as immunosuppressants in patients
      with autoimmune disorders and transplant recipients. However, these drugs worsen
      hepatitis C virus (HCV) recurrence after liver transplantation, suggesting that
      they may directly exacerbate HCV infection. METHODS: The influence of
      immunosuppressive drugs on HCV replication, assembly, and entry was assessed in
      Huh-7.5 cells and primary human hepatocytes using cell culture- and patient
      derived HCV. Replication was quantified by immunofluorescence, luciferase assays,
      quantitative reverse-transcriptase polymerase chain reaction, or core enzyme
      linked immunosorbent assays. Expression of HCV entry factors was evaluated by
      cell sorting and immunoblot analyses. RESULTS: Glucocorticosteroids slightly
      reduced HCV RNA replication but increased efficiency of HCV entry by up to 10
      fold. This was independent of HCV genotype but specific to HCV because vesicular
      stomatitis virus glycoprotein-dependent infection was not affected by these
      drugs. The increase in HCV entry was accompanied by up-regulation of messenger
      RNA and protein levels of occludin and the scavenger receptor class B type I-2
      host cell proteins required for HCV infection; increase of entry by
      glucocorticosteroids was ablated by RU-486, an inhibitor of glucocorticosteroid
      signaling. Glucocorticosteroids increased propagation of cell culture-derived HCV
      approximately 5- to 10-fold in partially differentiated human hepatoma cells and
      increased infection of primary human hepatocytes by cell culture- and patient
      derived HCV. CONCLUSIONS: Glucocorticosteroides specifically increase HCV entry
      by up-regulating the cell entry factors occludin and scavenger receptor class B
      type I. Our data suggest that the potential effects of high-dose
      glucocorticosteroids on HCV infection in vivo may be due to increased HCV
      dissemination.

PMID- 20152836
TI  - Short-chain fatty acids regulate the enteric neurons and control gastrointestinal
      motility in rats.
AB  - BACKGROUND & AIMS: Little is known about the environmental and nutritional
      regulation of the enteric nervous system (ENS), which controls gastrointestinal
      motility. Short-chain fatty acids (SCFAs) such as butyrate regulate colonic
      mucosa homeostasis and can modulate neuronal excitability. We investigated their
      effects on the ENS and colonic motility. METHODS: Effects of butyrate on the ENS
      were studied in colons of rats given a resistant starch diet (RSD) or intracecal
      perfusion of SCFAs. Effects of butyrate were also studied in primary cultures of
      ENS. The neurochemical phenotype of the ENS was analyzed with antibodies against
      Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS)
      and by quantitative polymerase chain reaction. Signaling pathways involved were
      analyzed by pharmacologic and molecular biology methods. Colonic motility was
      assessed in vivo and ex vivo. RESULTS: In vivo and in vitro, RSD and butyrate
      significantly increased the proportion of ChAT- but not nNOS-immunoreactive
      myenteric neurons. Acetate and propionate did not reproduce the effects of
      butyrate. Enteric neurons expressed monocarboxylate transporter 2 (MCT2). Small
      interfering RNAs silenced MCT2 and prevented the increase in the proportion of
      ChAT- immunoreactive neurons induced by butyrate. Butyrate and trichostatin A
      increased histone H3 acetylation in enteric neurons. Effects of butyrate were
      prevented by inhibitors of the Src signaling pathway. RSD increased colonic
      transit, and butyrate increased the cholinergic-mediated colonic circular muscle
      contractile response ex vivo. CONCLUSION: Butyrate or histone deacetylase
      inhibitors might be used, along with nutritional approaches, to treat various
      gastrointestinal motility disorders associated with inhibition of colonic
      transit.

PMID- 20152837
TI  - The genome of the nematode Pristionchus pacificus encodes putative homologs of
      RXR/Usp and EcR.
AB  - Ecdysteroid signaling is an important regulator of arthropod development and
      reproduction. However, the role of ecdysteroid signaling in another Ecdysozoan
      animal, the nematode, remains unclear. We report here the identification,
      cloning, and temporal expression of genes encoding putative homologs of the two
      nuclear receptor components of the ecdysone receptor, RXR/Usp (NR2B) and EcR
      (NR1H), in the nematode Pristionchus pacificus. The P. pacificus genes Ppa-pnhr-1
      and Ppa-pnhr-2 encode nuclear receptors with strong sequence similarity to
      RXR/Usp and EcR, respectively. Maximum likelihood analysis incorporating both DNA
      binding and ligand-binding domains places the two proteins in the NR2B and NR1H
      groups with strong bootstrap support. RT-PCR analysis reveals that both Ppa-pnhr
      1 and Ppa-pnhr-2 are expressed during larval development and that Ppa-pnhr-1
      expression oscillates with the molting cycle. The identification of a putative
      ecdysone receptor in a nematode amenable to genetic analysis provides a powerful
      system to investigate the function and evolution of ecdysone receptor signaling
      in the Nematoda.

PMID- 20152838
TI  - Seasonal changes in concentrations of plasma LH and prolactin associated with the
      advance in the development of photorefractoriness and molt by high temperature in
      the starling.
AB  - In a study on starlings (Sturnus vulgaris) kept on a simulated annual cycle in
      photoperiod, temperature had no effect on the timing or rate of testicular
      maturation but high temperature resulted in an advance in the timing of
      testicular regression and molt (Dawson, 2005). This study asks whether the
      earlier gonadal regression in response to higher temperature represents a central
      neuroendocrine response to temperature, and secondly, whether prolactin plays a
      role in the earlier regression. Castrated starlings were kept on a simulated
      annual cycle of photoperiod at either 8 or 18 degrees C. Circulating LH and
      prolactin concentrations were measured and the progress of the post-nuptial molt
      was recorded as an external indicator of the development of photorefractoriness.
      Additionally plasma prolactin was measured in samples taken from intact male and
      female starlings in the 2005 study. In castrated birds, LH concentrations
      decreased three weeks earlier at 18 degrees C. These birds also showed the same
      three week advance in molt as males and females in the earlier study. This
      demonstrates that the advance in regression caused by higher temperatures
      probably results from a central neuroendocrine mechanism, i.e., an advance in
      photorefractoriness, rather than an effect at the level of the gonads.
      Temperature had a highly significant effect on the changes in prolactin - peak
      prolactin occurred three weeks earlier at 18 degrees C. However, there was no
      clear consistent significant difference in prolactin between the two temperatures
      in advance of the onset of photorefractoriness, so the advance in
      photorefractoriness may not be mediated by prolactin. The higher temperature
      resulted in a significantly earlier decrease in prolactin and this may be
      causally related to the advance in molt.

PMID- 20152839
TI  - Asynchronic steroid activity of Leydig and Sertoli cells related to spermatogenic
      and testosterone cycle in Phymaturus antofagastensis.
AB  - The severe environments where Phymaturus lizards inhabit in the Andes highlands
      and in Patagonia, Argentina, impose restrictions on their reproduction, offering
      a framework for the development of life history strategies to overcome hard
      weather conditions. Among them, prolonged female cycles, asynchrony between sexes
      in receptivity, and sperm storage in males, were described. Asynchrony in the
      reproductive timing between males and females is a consequence of different
      energy requirements for gametogenesis, and often imply the existence of cellular
      mechanisms to enhance fertilization, such as the asynchronic steroid synthesis
      between testicular compartments, allowing gametogenesis independently of mating.
      In the present study ultrastructural and hormone assays were combined for the
      first time in liolaemids. Specifically, morphological features of steroid
      activity in Leydig and Sertoli cells, and serum testosterone concentrations have
      been studied in the lizard Phymaturus antofagastensis. Leydig and Sertoli cells
      presented morphological features characteristic of steroid synthesis during the
      spermatogenesis, and evident asynchronic steroid production between testicular
      compartments. Active Sertoli cells and inactive Leydig cells were observed in
      spring and autumn, while in mid-summer their steroid activity was synchronic in
      coincidence with maximal abundance of spermatozoa in epididymis. Serum
      testosterone concentration was at its maximum in mid-summer (126-230 ng ml(-1)),
      and minimum in late spring (4-24 ng ml(-1)) and early autumn (2-17 ng ml(-1)). In
      view of these results, P. antofagastensis males show an original approach to
      adjust their reproductive activity to physiological and environmental constraints
      at high latitudes and altitudes in the Andean highlands of Argentina.

PMID- 20152840
TI  - The activity of cardiac myocytes reflects a confluence of a multitude of
      electrical and chemical signals that promote and control the ability of the
      myocytes to shorten and develop force.

PMID- 20152841
TI  - Unfinished stories on viral quasispecies and Darwinian views of evolution.
AB  - Experimental evidence that RNA virus populations consist of distributions of
      mutant genomes, termed quasispecies, was first published 31 years ago. This work
      provided the earliest experimental support for a theory to explain a system that
      replicated with limited fidelity and to understand the self-organization and
      adaptability of early life forms on Earth. High mutation rates and quasispecies
      dynamics of RNA viruses are intimately related to both viral disease and
      antiviral treatment strategies. Moreover, the quasispecies concept is being
      applied to other biological systems such as cancer research in which cellular
      mutant spectra can be also detected. This review addresses some of the unanswered
      questions regarding viral and theoretical quasispecies concepts as well as more
      practical aspects concerning resistance to antiviral treatments and pathogenesis.

PMID- 20152842
TI  - How to resolve the SLOSS debate: lessons from species-diversity models.
AB  - The SLOSS debate--whether a single large reserve will conserve more species than
      several small--of the 1970s and 1980s never came to a resolution. The first rule
      of reserve design states that one large reserve will conserve the most species, a
      rule which has been heavily contested. Empirical data seem to undermine the
      reliance on general rules, indicating that the best strategy varies from case to
      case. Modeling has also been deployed in this debate. We may divide the modeling
      approaches to the SLOSS enigma into dynamic and static approaches. Dynamic
      approaches, covered by the fields of island equilibrium theory of island
      biogeography and metapopulation theory, look at immigration, emigration, and
      extinction. Static approaches, such as the one in this paper, illustrate how
      several factors affect the number of reserves that will save the most species.
      This article approaches the effect of different factors by the application of
      species-diversity models. These models combine species-area curves for two or
      more reserves, correcting for the species overlap between them. Such models
      generate several predictions on how different factors affect the optimal number
      of reserves. The main predictions are: Fewer and larger reserves are favored by
      increased species overlap between reserves, by faster growth in number of species
      with reserve area increase, by higher minimum-area requirements, by spatial
      aggregation and by uneven species abundances. The effect of increased distance
      between smaller reserves depends on the two counteracting factors: decreased
      species density caused by isolation (which enhances minimum-area effect) and
      decreased overlap between isolates. The first decreases the optimal number of
      reserves; the second increases the optimal number. The effect of total reserve
      system area depends both on the shape of the species-area curve and on whether
      overlap between reserves changes with scale. The approach to modeling presented
      here has several implications for conservational strategies. It illustrates well
      how the SLOSS enigma can be reduced to a question of the shape of the species
      area curve that is expected or generated from reserves of different sizes and a
      question of overlap between isolates (or reserves).

PMID- 20152843
TI  - Motif discovery using an immune genetic algorithm.
AB  - In this paper, a new immune genetic algorithm for motif discovery is proposed.
      The algorithm adopts concentration regulation mechanism to maintain the
      population diversity and vaccine mechanism to inhibit degeneracy during
      evolution. Experimental results have demonstrated the method's capacity to find
      known motifs in relatively long promoter sequences and multiple motifs within a
      single run.

PMID- 20152844
TI  - Dairy beverages and energy balance.
AB  - High dairy intakes have been associated with lower rates of obesity in
      observational studies, but mechanisms to explain the association are lacking. A
      high intake of dairy protein reduces spontaneous food intake and may be one
      important mechanism, but more specific effects of dairy calcium seem to exist. We
      have found that high versus low calcium intakes from dairy products had no effect
      on 24-h energy expenditure or substrate oxidation rates, but fecal fat excretion
      increased approximately 2.5-fold on the high-calcium diets. In a meta-analysis of
      intervention studies we found that increasing dairy calcium intake by 1200mg/day
      resulted in increased fecal fat excretion by 5.2 (1.6-8.8) g/day. Newer research
      shows that humans possess taste receptors for calcium in the gastrointestinal
      tract and that signaling may be linked to appetite regulation. A new line of
      evidence suggests that an inadequate calcium intake during an energy restricted
      weight loss program may trigger hunger and impair compliance to the diet. These
      mechanisms may be part of the explanation for the protective effects of dairy
      products with regard to obesity and metabolic syndrome.

PMID- 20152845
TI  - Effects of anesthesia and blood sampling techniques on plasma metabolites and
      corticosterone in the rat.
AB  - Blood is routinely sampled from laboratory animals in biomedical research, and
      many of the commonly applied sampling techniques require anesthesia. Acute
      effects of many sampling and anesthesia procedures may confound the results, but
      those effects are incompletely characterized. We here compare the effects of four
      common anesthesia procedures (inhalation anesthesia with ether (EA) or isoflurane
      (IA) and intraperitoneal injection anesthesia with xylazin/ketamine (XKA) or
      medetomidine/midazolam/fentanyl (MMFA)) on plasma concentrations of glucose,
      lactate, non-esterified fatty acids (NEFAs), and corticosterone in blood obtained
      from a previously implanted jugular vein (JV) catheter with the effect of JV
      blood sampling from non-anesthetized, freely-moving rats (JV-NA). Also, we
      included in the comparison two other blood sampling procedures usually performed
      without anesthesia (NA), i.e., puncture of the saphenic vein (SV) and tail
      incision (TI). Whereas the control procedure (JV-NA) did not significantly affect
      any of the target parameters, plasma glucose increased from 14 (JV-IA) to 44 (JV
      MMFA) % (all Ps=0.05 when compared with the control procedure) in all blood
      samples collected in anesthesia and was 12 and 14% lower (both Ps<0.05) in SV-NA
      and TI-NA samples, respectively. Plasma lactate increased from 74 (JV-IA) to 226%
      (SV-NA) (all Ps<0.05) with all sampling and anesthesia procedures except for JV
      XKA and JV-MMF. Plasma NEFAs increased to 52% (P<0.05) with the TI-NA procedure
      and appeared to decrease with the JV-IA and JV-MMFA procedures (both Ps>0.05).
      Finally, only the JV-EA and the JV-MMFA procedures increased plasma
      corticosterone (+525 and +353%, respectively, both Ps< 0.05). The JV-IA and JV
      XKA procedures appeared to increase it as well, but these differences did not
      reach statistical significance. Thus, anesthesia and blood sampling procedures
      can have profound acute effects on plasma metabolite and hormone concentrations.
      This must be considered for the design and interpretation of blood sampling
      experiments in laboratory animals.

PMID- 20152846
TI  - Measuring persistent temporomandibular joint nociception in rats and two mice
      strains.
AB  - Temporomandibular joint (TMJ) pain has been reported to last for prolonged
      periods in humans. In rodents a variety of methods have been used to measure TMJ
      nociception, but for most of these methods the period of measurement has been
      minutes to a couple of hours. In addition, most measurement protocols required
      restraint or training of the animal. Previous studies from our laboratory
      demonstrated that feeding behavior, particularly meal duration, was an indicator
      of TMJ nociception in unrestrained and untrained male and female Sprague-Dawley
      rats for up to two days. In this study, we first found that injection of complete
      Freund's adjuvant (CFA) into the TMJ of rats significantly lengthened meal
      duration for 19 days and also decreased meal frequency for 42 days.
      Interestingly, the meal duration varied significantly from day to day within the
      19 day period. TMJ interleukin-1 beta (IL-1 beta) and calcitonin gene-related
      peptide (CGRP) were significantly elevated in the TMJ tissues of CFA-injected
      animals and the level of these markers was attenuated as the meal duration
      decreased with time. Control animals injected with saline into the TMJ or CFA
      into the knee did not show a significant lengthening in meal duration but did
      show a decrease in meal frequency. In a second study, DBA/1LacJ mice given TMJ
      CFA injections showed a significantly lengthened meal duration on four of the
      seven days measured using end-of-the meal definition of 5 or 10 min. No other
      meal pattern changed significantly. Two days post-CFA injection, the DBA/1LacJ
      mice showed significantly elevated interleukin-6 (IL-6), but not elevated IL-1
      beta. Seven days post-injection, both IL-6 and IL-1 beta were significantly
      elevated. No change in CGRP was detected. In this study C57Bl/6 mice also
      received TMJ CFA injections, but they did not show a lengthening in any meal
      pattern or significant increases in IL-1 beta, IL-6 or CGRP. Our data show, for
      the first time, that meal duration can be used to measure CFA-induced nociception
      in the TMJ over the course of several weeks in unrestrained rats and for up to
      seven days in the DBA/1LacJ mouse strain. In addition, C57Bl/6 mice are resistant
      to CFA-induced TMJ nociception at the same dose used in the DBA/1LacJ mice.

PMID- 20152847
TI  - Effect of dexamethasone on peripheral blood leukocyte immune response in bile
      pancreatic duct obstruction-induced acute pancreatitis.
AB  - Our aim was to analyze the effects of dexamethasone (Dx) (1mg/kg),
      prophylactically or therapeutically administered, on the inflammatory response
      triggered by peripheral blood leukocytes during acute pancreatitis (AP) induced
      in rats by bile-pancreatic duct obstruction (BPDO) and their consequences in the
      progress of the disease. Flow cytometry was used to analyze the distribution of
      the major leukocyte populations, the CD45 expression and the activated state of
      monocytes as reflected by the membrane-bound intercellular adhesion molecule-1
      (ICAM-1) and the production of tumor necrosis factor-alpha (TNF-alpha) and
      monocyte chemoattract protein-1 (MCP-1) in response to lipopolysaccaride (LPS).
      Interleukin-6 (IL-6) plasma levels, pancreatic fluid content and histology of
      pancreas sections were also evaluated. Dx, given either before or after AP,
      blunted the monocyte increase induced by BPDO-induced AP, but did not change
      lymphocyte and neutrophil counts. Membrane-bound ICAM-1 expression did not vary
      in circulating monocytes during BPDO, either in Dx-treated or non-treated rats.
      Both Dx treatments inhibited TNF-alpha and MCP-1 production in non-stimulated and
      LPS-stimulated monocytes, whose response was found to be higher than in controls
      from early AP. Leukocyte CD45 expression was found to be reduced in rats with AP
      and shifted to control values in Dx-post-treated rats. Cytokinemia as well as
      pancreatic edema and leukocyte infiltration found in BPDO rats were reduced by Dx
      given either before or after AP. We conclude that prophylactic and therapeutic Dx
      treatments inhibited the inflammatory response triggered by circulating
      leukocytes in rats with BPDO-induced AP, thus contributing to reducing the
      severity of the disease.

PMID- 20152848
TI  - Determination of 17beta-oestradiol by fluorescence immunoassay with streptavidin
      conjugated quantum dots as label.
AB  - A sensitive and selective method for the determination of 17beta-oestradiol by
      fluorescence immunoassay (FIA) was established on the basis of quantum dots (QDs)
      as label. The complex of biotin-labelled anti-rabbit IgG and strepavidin
      conjugated by quantum dots (QD-SA) was regarded as a probe in this system and the
      strepavidin-biotin system as signal amplification system. After optimising the
      conditions of the immunoreaction, such as the concentration of the reagent and
      the pH of the buffer solution, the linear range and the limit of detection of
      17beta-oestradiol were 0.01-10,000ngml(-1) and 0.00542ngml(-1), respectively.
      This method was applied to determine oestradiol in water samples, with the
      percent recoveries in the range of 86-113%.

PMID- 20152850
TI  - Scombroid poisoning: a review.
AB  - Scombroid poisoning, also called histamine fish poisoning, is an allergy-like
      form of food poisoning that continues to be a major problem in seafood safety.
      The exact role of histamine in scombroid poisoning is not straightforward.
      Deviations from the expected dose-response have led to the advancement of various
      possible mechanisms of toxicity, none of them proven. Histamine action levels are
      used in regulation until more is known about the mechanism of scombroid
      poisoning. Scombroid poisoning and histamine are correlated but complicated.
      Victims of scombroid poisoning respond well to antihistamines, and chemical
      analyses of fish implicated in scombroid poisoning generally reveal elevated
      levels of histamine. Scombroid poisoning is unique among the seafood toxins since
      it results from product mishandling rather than contamination from other trophic
      levels. Inadequate cooling following harvest promotes bacterial histamine
      production, and can result in outbreaks of scombroid poisoning. Fish with high
      levels of free histidine, the enzyme substrate converted to histamine by
      bacterial histidine decarboxylase, are those most often implicated in scombroid
      poisoning. Laboratory methods and screening methods for detecting histamine are
      available in abundance, but need to be compared and validated to harmonize
      testing. Successful field testing, including dockside or on-board testing needed
      to augment HACCP efforts will have to integrate rapid and simplified detection
      methods with simplified and rapid sampling and extraction. Otherwise, time
      consuming sample preparation reduces the impact of gains in detection speed on
      the overall analysis time.

PMID- 20152849
TI  - Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical
      strategy assessment using multidimensional multivariate statistic analysis.
AB  - Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing
      mushroom species. In addition to absence of antidote, no chemotherapeutic
      consensus was reported. The aim of the present study is to perform a
      retrospective multidimensional multivariate statistic analysis of 2110 amatoxin
      poisoning clinical cases, in order to optimize therapeutic decision-making. Our
      results allowed to classify drugs as a function of their influence on one major
      parameter: patient survival. Active principles were classified as first
      intention, second intention, adjuvant or controversial pharmaco-therapeutic
      clinical intervention. We conclude that (1) retrospective multidimensional
      multivariate statistic analysis of complex clinical dataset might help future
      therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and
      putatively ceftazidime are clearly associated, in amatoxin poisoning context,
      with higher level of patient survival.

PMID- 20152851
TI  - Comparative effects of lantadene A and its reduced metabolite on mitochondrial
      bioenergetics.
AB  - Lantana (Lantana camara Linn.) is a noxious weed to which certain medicinal
      properties have been attributed, but its ingestion has been reported to be highly
      toxic to animals and humans, especially in the liver. The main hepatotoxin in
      lantana leaves is believed to be the pentacyclic triterpenoid lantadene A (LA),
      but the precise mechanism by which it induces hepatotoxicity has not yet been
      established. This work addressed the action of LA and its reduced derivative
      (RLA) on mitochondrial bioenergetics. At the concentration range tested (5-25
      microM), RLA stimulated state-4 respiration, inhibited state-3 respiration,
      circumvented oligomycin-inhibited state-3 respiration, dissipated membrane
      potential and depleted ATP in a concentration-dependent manner. However, LA did
      not stimulate state-4 respiration, nor did it affect the other mitochondrial
      parameters to the extent of its reduced derivative. The lantadenes didn't inhibit
      the CCCP-uncoupled respiration but increased the ATPase activity of intact
      coupled mitochondria. The ATPase activity of intact uncoupled or disrupted
      mitochondria was not affected by the compounds. We propose, therefore, that RLA
      acts as a mitochondrial uncoupler of oxidative phosphorylation, a property that
      arises from the biotransformation (reduction) of LA, and LA acts in other
      mitochondrial membrane components rather than the ATP synthase affecting the
      mitochondrial bioenergetics. Such effects may account for the well-documented
      hepatoxicity of lantana.

PMID- 20152852
TI  - Lonomia obliqua (Lepidoptera, Saturniidae) caterpillar bristle extract induces
      direct lysis by cleaving erythrocyte membrane glycoproteins.
AB  - Lonomia obliqua caterpillar bristle extract induces hemolysis in vitro on washed
      human and rat erythrocytes, in either the absence or presence of exogenous
      lecithin. In the former condition, phospholipases A(2) are key enzymes involved
      in hemolysis. However, the mechanism whereby this extract causes direct hemolysis
      is not known. Thus, the aim of this study was to investigate the hemolytic
      mechanism of the crude extract of the caterpillar L. obliqua on human
      erythrocytes in the absence of lecithin. The extract significantly increased the
      erythrocyte osmotic fragility and promoted the removal of glycophorins A and C,
      and band 3 from the erythrocyte membrane. The use of Ca2+ and Mg2+ ions
      significantly potentiated glycoprotein removal, remarkably of erythrocyte band 3.
      The composition of fatty acids was analyzed by HPLC in both L. obliqua
      caterpillar bristle extract and human erythrocyte membranes incubated with the
      extract. The levels of unsaturated fatty acids were remarkably augmented in
      erythrocytes incubated with the extract than in control erythrocytes, modifying
      thereby the saturated/unsaturated fatty acid ratio. Altogether, evidence is
      provided here that the interplay of at least three mechanisms of action accounts
      for the direct activity of the bristle extract on erythrocyte membrane, leading
      to hemolysis: the removal of glycoproteins and band 3; the insertion of fatty
      acids; and the action of phospholipases. Such mechanisms might affect erythrocyte
      flexibility and deformability, which may induce hemolysis by increasing
      erythrocyte fragility. However, whether the direct hemolytic activity of L.
      obliqua caterpillar is the major cause of intravascular hemolysis during
      envenomation still needs further investigation.

PMID- 20152853
TI  - The spatial distribution of receptive field changes in a model of peri-saccadic
      perception: predictive remapping and shifts towards the saccade target.
AB  - At the time of an impending saccade receptive fields (RFs) undergo dynamic
      changes, that is, their spatial profile is altered. This phenomenon has been
      observed in several monkey visual areas. Although their link to eye movements is
      obvious, neither the exact pattern nor their function is fully clear. Several RF
      shifts have been interpreted in terms of predictive remapping mediating visual
      stability. In particular, even prior to saccade onset some cells become
      responsive to stimuli presented in their future, post-saccadic RF. In visual area
      V4, however, the overall effect of RF dynamics consists of a shrinkage and shift
      of RFs towards the saccade target. These observations have been linked to a pre
      saccadically enhanced processing of the future fixation. In order to better
      understand these seemingly different outcomes, we analyzed the RF shifts
      predicted by a recently proposed computational model of peri-saccadic perception
      (Hamker, Zirnsak, Calow, & Lappe, 2008). This model unifies peri-saccadic
      compression, pre-saccadic attention shifts, and peri-saccadic receptive field
      dynamics in a common framework of oculomotor reentry signals in extrastriate
      visual cortical maps. According to the simulations that we present in the current
      paper, a spatially selective oculomotor feedback signal leads to RF dynamics
      which are both consistent with the observations made in studies aiming to
      investigate predictive remapping and saccade target shifts. Thus, the seemingly
      distinct experimental observations could be grounded in the same neural mechanism
      leading to different RF dynamics dependent on the location of the RF in visual
      space.

PMID- 20152854
TI  - Viscoelastic adlayers of collagen and lysozyme studied using quartz crystal
      microbalance with dissipation monitoring.
AB  - In this study the effects of molecular structure of proteins on their adsorption
      behaviour and viscoelasticity are investigated using a QCM-D method. The
      adsorption measurements show that spherical lysozyme is rapidly adsorbed on the
      gold surface as a stiff monolayer, as indicated by a sharp drop in the
      oscillation frequency (Deltaf) of the sensor, and by a very small increase in the
      energy dissipation of the adlayer (DeltaD). Fibrous calfskin collagen (CSC) is,
      however, adsorbed on the same surface rather slowly in two steps to form a thick
      and soft multilayer (large Deltaf and DeltaD) at pH 3 in salt-free conditions.
      The two-step adsorption is not observed for stiffly aggregated CSC. This study
      clearly demonstrates that the polymer structure strongly affects not only how
      adsorption develops but also the viscoelastic properties of the adlayer.

PMID- 20152855
TI  - Dopaminergic modulation of cognition across the life span.

PMID- 20152856
TI  - Comparison of same day versus delayed enumeration of TB-specific T cell
      responses.
AB  - BACKGROUND/OBJECTIVE: Flexibility in sample processing may improve test utility
      of the quantitative antigen-specific T cell assay (T-SPOT.TB). We investigated
      whether delayed sample processing with and without the use of T-Cell Xtend, a
      proprietary reagent, impacted upon test accuracy. METHODS: Blood samples obtained
      from 363 sequentially recruited tuberculosis suspects or treated patients were
      processed immediately (day 0) and at different times after receipt of the sample
      [approximately 24-h (day 1) or approximately 32-h (day 2)] with and without
      adding T-Cell Xtend. RESULTS: T-Cell-Xtend-independent median ELISPOT counts
      (spot forming cells per million peripheral blood mononuclear cells) were
      significantly higher at day 1 versus day 0 (114 vs. 100; n=66; p=0.03); inter
      time-point agreement between the results was 95.45% and the conversion/reversion
      rate was 4.55%. By contrast, counts on day 0 without T-Cell Xtend versus day 1
      with T-Cell Xtend were similar (56 vs. 56; n=215), inter-time-point agreement
      between the results was 97.17%, and the conversion/reversion rate was 2.83%.
      Counts performed at day 2 with T-Cell Xtend were not significantly different from
      day 0. These findings were independent of HIV status. CONCLUSION: There was high
      agreement between results when samples were processed immediately and after a 24
      h delay. However, although the use of T-Cell Xtend appeared to reduce the number
      of conversions/reversions this reduction was not statistically significant.
      Larger studies are required to clarify these findings.

PMID- 20152857
TI  - Biphenyl phosphatidylcholine: a promoter of liposome deformation and bicelle
      collective orientation by magnetic fields.
AB  - Membrane lipids with long saturated or unsaturated acyl chains are usually not
      sensitive to magnetic fields. We report in this review a few exceptions with
      potential use in structural biology or drug delivery. Mixtures of short and long
      chain phospholipids called bicelles can form discs-shaped nanoobjects (40nm) that
      can indeed be oriented in magnetic fields. This is due to the cooperative effect
      of the small diamagnetic negative anisotropic susceptibility of each of the
      individual lipids that build up a macroscopic magnetic moment that orients in the
      field like a compass. Chain saturated lipids have a tendency to be oriented with
      their long molecular axis perpendicular to the field, thus leading to a disc
      plane with a parallel orientation. Newly synthesized phosphatidylcholine (PC)
      containing a biphenyl group in one of its acyl chains (1-tetradecanoyl-2-(4-(4
      biphenyl)butanoyl)-sn-glycero-3-PC, TBBPC) shows very unusual macroscopic
      orienting properties due to the strong positive anisotropy of the biphenyl
      diamagnetic susceptibility. Mixing with short chain lipids leads to bicelles of
      80nm diameter that are oriented by magnetic fields such that the disc plane is
      perpendicular to the field. Tuning the lipid molecular structure thus affords
      controlling the orientation of this "molecular goniometer". Because the magnetic
      alignment is remnant for tens of hours even outside the field, applications in
      structural biology and biotechnology, are discussed. Of great interest,
      micrometer-sized liposomes made from such a new lipid are strongly deformed into
      oblates when placed in a magnetic field greater than a few Tesla. Increasing the
      magnetic field leads to even greater deformations which could potentially be used
      in medicine for specific drug delivery purposes, under magnetic resonance
      imaging.

PMID- 20152858
TI  - N-acylethanolamine metabolism with special reference to N-acylethanolamine
      hydrolyzing acid amidase (NAAA).
AB  - N-acylethanolamines (NAEs) constitute a class of bioactive lipid molecules
      present in animal and plant tissues. Among the NAEs, N-arachidonoylethanolamine
      (anandamide), N-palmitoylethanolamine, and N-oleoylethanolamine attract much
      attention due to cannabimimetic activity as an endocannabinoid, anti-inflammatory
      and analgesic activities, and anorexic activity, respectively. In mammalian
      tissues, NAEs are formed from glycerophospholipids through the phosphodiesterase
      transacylation pathway consisting of Ca(2+)-dependent N-acyltransferase and N
      acylphosphatidylethanolamine-hydrolyzing phospholipase D. Recent studies revealed
      the presence of alternative pathways and enzymes responsible for the NAE
      formation. As for the degradation of NAEs, fatty acid amide hydrolase (FAAH),
      which hydrolyzes NAEs to fatty acids and ethanolamine, plays a central role.
      However, a lysosomal enzyme referred to as NAE-hydrolyzing acid amidase (NAAA)
      also catalyzes the same reaction and may be a new target for the development of
      therapeutic drugs. In this article we discuss recent progress in the studies on
      the enzymes involved in the biosynthesis and degradation of NAEs with special
      reference to NAAA.

PMID- 20152859
TI  - Genetic influences on cognitive functions in the elderly: a selective review of
      twin studies.
AB  - In this review, we examined the published reports on the heritability of
      cognitive functioning in old age. Twenty-four papers from five study centers,
      comprising of participants with a mean age of 65 years and above were examined.
      The comparability of findings from different studies was compromised by the use
      of different measures for the same cognitive domain, and with large scale twin
      studies in cognitive aging limited to a few Scandinavian countries. While the
      results from cross-sectional samples appear to lend support for the notion that
      heritability of cognitive functions decreases in the elderly, the findings are
      best considered inconclusive. Longitudinal reports show little evidence for
      genetic effects, but an increase in unique environmental influences on the rate
      of cognitive change as age increases. In relation to the two prominent theories
      of cognitive aging, the genetic influence on processing speed as a major
      contributor to cognitive aging has been indicated in three reports, whereas the
      genetic relationship between executive functions and other cognitive functions
      has not been explored. Only two studies have focused on sex difference and did
      not find sex-specific genetic influence in cognitive abilities. This review
      indicates that there are complex relationships between heritability,
      environmental influence, and cognitive functions in the elderly. It highlights
      the need for more research, with consistent and appropriate cognitive measures,
      with data obtained from larger and more geographically and culturally diverse
      twin samples.

PMID- 20152860
TI  - Computational processing of optical measurements of neuronal and synaptic
      activity in networks.
AB  - Imaging of optical reporters of neural activity across large populations of
      neurones is a widely used approach for investigating the function of neural
      circuits in slices and in vivo. Major challenges in analysing such experiments
      include the automatic identification of neurones and synapses, extraction of
      dynamic signals, and assessing the temporal and spatial relationships between
      active units in relation to the gross structure of the circuit. We have developed
      an integrated set of software tools, named SARFIA, by which these aspects of
      dynamic imaging experiments can be analysed semi-automatically. Key features are
      image-based detection of structures of interest using the Laplace operator,
      determining the positions of units in a layered network, clustering algorithms to
      classify units with similar functional responses, and a database to store,
      exchange and analyse results across experiments. We demonstrate the use of these
      tools to analyse synaptic activity in the retina of live zebrafish by multi
      photon imaging of SyGCaMP2, a genetically encoded synaptically localised calcium
      reporter. By simultaneously recording activity across tens of bipolar cell
      terminals distributed throughout the IPL we made a functional map of the ON and
      OFF signalling channels and found that these were only partially separated. The
      automated detection of signals across many neurones in the retina allowed the
      reliable detection of small populations of neurones generating "ectopic" signals
      in the "ON" and "OFF" sublaminae. This software should be generally applicable
      for the analysis of dynamic imaging experiments across hundreds of responding
      units.

PMID- 20152861
TI  - ImmunoAT method: An initial assessment for the detection of abnormal isoforms of
      prion protein in formalin-fixed and paraffin-embedded tissues.
AB  - The AT-tailing method is a labelling technique that utilises oligo(dA-dT)
      dependent signal amplification. In this study, a new immunohistochemical
      application of the immunoAT method was developed. This method uses an oligo(dA
      dT)-conjugated primary antibody (direct immunoAT method) or an oligo(dA-dT)
      conjugated secondary antibody (indirect immunoAT method). Fifteen-base oligo(dA
      dT)-conjugated antibodies (IgG-ATs) were prepared in advance by conjugating
      maleimide-activated oligo(dA-dT) to IgG via free sulfhydryl residues that had
      been introduced on the surface of IgG using Traut's reagent. Following the
      reaction with the target antigen and the IgG-AT, oligo(dA-dT) was elongated by
      DeltaTth DNA polymerase in the presence of dATP, dTTP and biotinylated dUTP,
      consequently labelling the antigen-antibody complex with a large amount of
      biotin. To initially evaluate the immunoAT method, the presence or absence of
      prion protein (PrP(sc)) was determined in formalin-fixed and paraffin-embedded
      sections of the medulla oblongata of cattle which had been under active
      surveillance for bovine spongiform encephalopathy. Sections were examined using
      direct and indirect immunoAT methods and the EnVision+ system (Dako) under
      conditions that were identical except for the differing IgG-AT and AT-tailing
      methods. PrP(sc) detection was consistent using all three methods. The clearest
      signals were obtained using the indirect immunoAT method, suggesting significant
      potential for this method.

PMID- 20152862
TI  - Evaluation of four enzyme linked immunosorbent assays for the detection of
      antibodies to infectious bursal disease in chickens.
AB  - The routine technique for detecting antibodies specific to infectious bursal
      disease virus is a serological evaluation by enzyme linked immunosorbent assay
      (ELISA) with preparations of whole virions as antigens. To avoid the use of
      complete virus in the standard technique, in-house VP2 and VP3 based ELISAs were
      developed. Accordingly, four types of indirect ELISAs viz., a commercial IDEXX
      ELISA kit, VP2 and or VP3 antigen based ELISAs and a whole virus ELISA were
      compared with the virus neutralization test. It was concluded that the
      sensitivity and specificity at receiver-operating characteristics (ROC) optimized
      cut-off of four ELISAs viz., IDEXX-ELISA, VP2-ELISA and VP3-ELISA indicated
      similar performance whereas whole virus antigen based ELISA showed poor
      performance in comparison to other ELISAs. Similarly the positive and negative
      likelihood ratio of four ELISAs at an optimized cut-off indicated IDEXX-ELISA to
      be the best among all the four ELISAs while the performance of rVP3-ELISA and
      rVP2-ELISA is good as compared to the whole virus ELISA. Finally, the area under
      the ROC curve (AUC) of four ELISAs which represented a summary statistics of the
      overall diagnostic performance of the test also indicated that the IDEXX-ELISA,
      VP3-ELISA and VP2-ELISA had similar and relatively better performance when
      compared to whole virus antigen-ELISA.

PMID- 20152863
TI  - Characterization and epitope mapping of monoclonal antibodies recognizing N
      terminus of Rep of porcine circovirus type 2.
AB  - Two genotypes of porcine circovirus (PCV) have been described, the non-pathogenic
      PCV1 and the pathogenic PCV2 in pigs. PCV-ORF1 encodes Rep and Rep' proteins
      which have identical N-terminal sequence (RepN) within each PCV strain, but RepN
      has only 88% similarity between PCV1 and PCV2. Purified RepN of PCV2 was used as
      an immunogen to produce monoclonal antibodies (mAbs). 11 mAbs were screened out
      and established, and they were divided into two groups according to Western blot
      and IFA results. One group, including 1C1, bound only PCV2-RepN, while the other,
      including 3D10, had cross reactivity with RepN of both PCV1 and PCV2. Epitope
      mapping indicated that 1C1 and 3D10 recognized the linear epitopes
      L(39)FDYFIVG(46) and K(99)EGNLLIE(106) in PCV2-RepN, respectively. Protein
      sequence alignment of RepN indicated L(39)FDYFIVG(46) is conserved in all PCV2 in
      NCBI database, whereas the PCV1 has amino acid substitutions V(41)C(42) in this
      region. mAb 3D10 could recognize all PCV because all natural mutations in its
      epitope did not affect its binding. The information about characteristics and
      epitope of monoclonal antibodies may be useful for the development of diagnostic
      methods for PCV2 and for analyzing the function of Rep and Rep' of PCV.

PMID- 20152864
TI  - Analytical and clinical performance evaluation of the cobas TaqScreen MPX Test
      for use on the cobas s 201 system.
AB  - Clinical specificity, analytical and clinical sensitivities, reproducibility, and
      subtype/genotype coverage of the cobas TaqScreen MPX Test, a multiplex nucleic
      acid test with expanded coverage of HIV variants, were determined. A total of
      72,281 blood donations were evaluated. The 95% limit of detection (LOD) for the
      MPX Test inclusive viruses was determined by testing six dilutions of WHO or
      Roche standards. Over 3000 high-risk and confirmed seropositive specimens were
      tested with the MPX and COBAS AmpliScreen Tests. Ten subtypes of HIV-1 Group M,
      HIV-1 Group O, HIV-2 A and B, HBV genotypes A-H, and HCV genotypes 1-6 were
      tested with the MPX Test. Reproducibility panels were evaluated at three testing
      sites across three lots. Clinical specificity in pools was 99.99%. There was one
      HBV yield case. The LODs for HIV-1 Group M, HCV, and HBV were 49, 11, and 3.8
      IU/mL, respectively, and 89 and 59.3 copies/mL for HIV-1 Group O and HIV-2,
      respectively. Concordance between the MPX and the AmpliScreen Tests was 94.9%.
      Clinical sensitivity based on AmpliScreen comparison was 97.8-99.5%. All
      genotype/subtype replicates were detected at three times the LOD. Reproducibility
      was 98.3-100%. In conclusion, the MPX Test is robust and covers HIV-1 Group O and
      HIV-2.

PMID- 20152866
TI  - Agarose stabilization of fragile biofilms for quantitative structure analysis.
AB  - Agarose was used to stabilize fragile biofilms cultivated in parallel plate flow
      cells prior to imaging by confocal laser scanning microscopy. An essential
      element to the success of the procedure was the application of a ceramic heat pad
      to the flow cell to maintain agarose fluidity until the biofilm was enveloped.
      Quantitative digital image analysis demonstrated the effectiveness of this
      technique for generating reproducible measurements of a three-dimensional biofilm
      structure. The described method will also benefit researchers who transport their
      flow cell-cultivated biofilms to a core facility for imaging.

PMID- 20152867
TI  - Optimization and evolution in metabolic pathways: global optimization techniques
      in Generalized Mass Action models.
AB  - Cells are natural factories that can adapt to changes in external conditions.
      Their adaptive responses to specific stress situations are a result of evolution.
      In theory, many alternative sets of coordinated changes in the activity of the
      enzymes of each pathway could allow for an appropriate adaptive readjustment of
      metabolism in response to stress. However, experimental and theoretical
      observations show that actual responses to specific changes follow fairly well
      defined patterns that suggest an evolutionary optimization of that response.
      Thus, it is important to identify functional effectiveness criteria that may
      explain why certain patterns of change in cellular components and activities
      during adaptive response have been preferably maintained over evolutionary time.
      Those functional effectiveness criteria define sets of physiological requirements
      that constrain the possible adaptive changes and lead to different operation
      principles that could explain the observed response. Understanding such operation
      principles can also facilitate biotechnological and metabolic engineering
      applications. Thus, developing methods that enable the analysis of cellular
      responses from the perspective of identifying operation principles may have
      strong theoretical and practical implications. In this paper we present one such
      method that was designed based on nonlinear global optimization techniques. Our
      methodology can be used with a special class of nonlinear kinetic models known as
      GMA models and it allows for a systematic characterization of the physiological
      requirements that may underlie the evolution of adaptive strategies.

PMID- 20152865
TI  - D2 antagonist during development decreases anxiety and infanticidal behavior in
      adult female prairie voles (Microtus ochrogaster).
AB  - On postnatal day 8, prairie vole pups were randomly assigned a treatment of
      1mg/kg SKF38393 (D1 agonist), quinpirole (D2 agonist), SCH23390 (D1 antagonist),
      eticlopride (D2 antagonist), or saline vehicle. As adults, females treated with
      eticlopride exhibited reduced anxiety-like behavior in an elevated plus maze and
      a reduction in infanticidal behavior. These behavioral effects were not seen in
      males. These data demonstrate that a single exposure to a D2 antagonist during
      development can have persistent, sex-specific effects on behavior into adulthood.

PMID- 20152868
TI  - Stability of Tobacco etch virus infectious clones in plasmid vectors.
AB  - Tobacco etch virus (TEV) has been traditionally used as a model to research many
      aspects of the molecular biology of plant RNA virus and, more recently,
      experimental evolution. However, the only plasmid of this virus species with an
      infectious clone that has been commonly available to research (pTEV7DA) is rather
      unstable when propagated in the bacterium Escherichia coli. Here, the TEV
      infectious clone contained in pTEV7DA is used to construct three new plasmids
      that allowed infecting the host plants from RNA transcripts synthesized in vitro
      (pMTEV), directly from plasmid DNA (p35TEV) and by agroinoculation (pGTEV). To
      increase stability of the three constructed plasmids in E. coli, superfluous
      vector sequences were removed and the virus expression cassettes were inserted
      between the plasmid replication origins and antibiotic selection markers in
      reverse orientation to the latter gene. Although the TEV cDNA in these three new
      plasmids is not interrupted by any exogenous sequence, they are more stable than
      the parental pTEV7DA during propagation in E. coli, indicating a major
      contribution of the plasmid context in virus cDNA stability. Using the different
      inocula produced from the three new plasmids the TEV infectivity was also
      compared. The results showed that agroinoculation is the most effective
      inoculation method and is where symptoms unfold earlier.

PMID- 20152869
TI  - Genomic diversity of sweet potato geminiviruses in a Brazilian germplasm bank.
AB  - Begomoviruses cause major diseases of sweet potato worldwide impairing
      considerably the yields of this important food staple. Since sweet potato plants
      are vegetatively propagated and globally transported, they are prone to
      accumulate and disseminate geminiviruses. Effective diagnostic tools are,
      therefore, desirable. We studied the genomic diversity of geminiviruses present
      in naturally-infected sweet potato accessions belonging to a Brazilian germplasm
      bank collection. Fifty-five samples from different sweet potato accessions
      displaying geminivirus-like symptoms were analyzed by combining rolling circle
      amplification (RCA) with restriction fragment length polymorphism (RFLP) and
      sequencing. The restriction enzyme MspI (HpaII) revealed diverse band patterns in
      55 samples and digestion with BamHI, SstI or PstI resulted in full-length sweet
      potato geminivirus DNAs of about 3 kb in 46 samples. In addition, smaller
      fragments were identified as either viral "Defective DNAs" (D-DNAs) or
      mitochondrial plasmid DNAs. The diversity of sweet potato-associated
      geminiviruses was found to be very high under Brazilian conditions.
      Representative viral full-length DNAs have been cloned and sequenced yielding two
      new tentative species, three strains and several variants of previously described
      sweet potato geminiviruses. Sequence comparisons identified footprints of
      recombination in their genomes underscoring the risk of generating new
      geminiviruses in vegetatively propagated germplasm bank material. The sites of
      recombination were found in conjunction with predicted hairpin structures. We
      propose diagnostic routines to screen germplasm bank material for geminiviruses
      by the rapid and reliable RCA/RFLP as the technique of choice.

PMID- 20152870
TI  - Chitosan-based nanogels for selective delivery of photosensitizers to macrophages
      and improved retention in and therapy of articular joints.
AB  - Macrophages play key roles in inflammatory disorders. Therefore, they are targets
      of treatments aiming at their local destruction in inflammation sites. However,
      injection of low molecular mass therapeutics, including photosensitizers, in
      inflamed joints results in their rapid efflux out of the joints, and poor
      therapeutic index. To improve selective uptake and increase retention of
      therapeutics in inflamed tissues, hydrophilic nanogels based on chitosan, of
      which surface was decorated with hyaluronate and which were loaded with one of
      three different anionic photosensitizers were developed. Optimal uptake of these
      functionalized nanogels by murine RAW 264.7 or human THP-1 macrophages as models
      was achieved after <4h incubation, whereas only negligible uptake by murine
      fibroblasts used as control cells was observed. The uptake by cells and the
      intracellular localization of the photosensitizers, of the fluorescein-tagged
      chitosan and of the rhodamine-tagged hyaluronate were confirmed by fluorescence
      microscopy. Photodynamic experiments revealed good cell photocytotoxicity of the
      photosensitizers entrapped in the nanogels. In a mouse model of rheumatoid
      arthritis, injection of free photosensitizers resulted in their rapid clearance
      from the joints, while nanogel-encapsulated photosensitizers were retained in the
      inflamed joints over a longer period of time. The photodynamic treatment of the
      inflamed joints resulted in a reduction of inflammation comparable to a standard
      corticoid treatment. Thus, hyaluronate-chitosan nanogels encapsulating
      therapeutic agents are promising materials for the targeted delivery to
      macrophages and long-term retention of therapeutics in leaky inflamed articular
      joints.

PMID- 20152871
TI  - Influence of prolonged treadmill running on appetite, energy intake and
      circulating concentrations of acylated ghrelin.
AB  - The effects of prolonged treadmill running on appetite, energy intake and
      acylated ghrelin (an appetite stimulating hormone) were examined in 9 healthy
      males over the course of 24h. Participants completed 2 experimental trials
      (exercise and control) in a randomised-crossover fashion. In the exercise trial
      participants ran for 90 min at 68.8 + or - 0.8% of maximum oxygen uptake followed
      by 8.5 h of rest. Participants returned to the laboratory on the following
      morning to provide a fasting blood sample and ratings of appetite (24 h
      measurement). No exercise was performed on the control trial. Appetite was
      measured within the laboratory using visual analogue scales and energy intake was
      assessed from ad libitum buffet meals. Acylated ghrelin was determined from
      plasma using an ELISA assay. Exercise transiently suppressed appetite and
      acylated ghrelin but each remained no different from control values in the hours
      afterwards. Furthermore, despite participants expending 5324 kJ during exercise
      there was no compensatory increase in energy intake (24 h energy intake; control
      17,191 kJ, exercise 17,606 kJ). These findings suggest that large energy deficits
      induced by exercise do not lead to acute compensatory responses in appetite,
      energy intake or acylated ghrelin.

PMID- 20152872
TI  - Effects of thought suppression on eating behaviour in restrained and non
      restrained eaters.
AB  - Recent research has shown that suppressing food related thoughts can cause a
      subsequent increase in consumption relative to groups not suppressing, or
      thinking about food. The present study examined whether the effects of thought
      suppression on subsequent eating behaviour would interact with participants
      restrained eating status. One hundred and sixteen female participants were split
      into three groups. One third suppressed thoughts of chocolate, one third thought
      about chocolate and the final third thought about anything they wished. Following
      this, participants took part in a task where they rated two brands of chocolate
      on several taste characteristics. Participants were unaware that the dependent
      variable was the amount of chocolate consumed and not taste preference.
      Participants also completed measures of dietary restraint, craving, guilt and
      thought suppression. Results indicated that restrained eaters in the suppression
      condition consumed significantly more chocolate than restrained eaters in the
      expression or control condition. Participants low on restraint ate statistically
      equivalent amounts in all three groups. In addition, participants reporting
      frequent use of thought suppression (assessed by the White Bear Suppression
      Inventory) reported greater chocolate cravings.

PMID- 20152873
TI  - Time course of oxidant markers and antioxidant defenses in subgroups of
      amyotrophic lateral sclerosis patients.
AB  - Oxidative stress markers have been found in nervous and peripheral tissues of
      familial and sporadic amyotrophic lateral sclerosis patients. Here, we evaluated
      the activity of some antioxidant enzymes glutathione peroxidase, glutathione
      reductase and Cu-Zn superoxide dismutase in erythrocyte, the marker of non
      enzymatic antioxidant response (total antioxidant status), as well as plasma
      reactive oxygen species, at the enrolment and during disease progression in 88
      patients affected by the sporadic form of amyotrophic lateral sclerosis. Our
      study has been performed along 72 months by grouping the patients according to
      the ALS functional rating score or rate of disease progression. Our results
      showed a significant impairment of erythrocytes glutathione peroxidase activity
      in all groups of patients that remained low during disease time course. SOD1
      activity significantly decreased along disease course in subjects with a more
      impaired functional status. A decreasing activity of all assayed enzymes was
      found in patients who have a faster disease progression rate. By this work we
      have the evidence that different ALS phenotypes present with different profile of
      enzymatic and non-enzymatic antioxidant response.

PMID- 20152874
TI  - A coding variant in NLRP1 is associated with autoimmune Addison's disease.
AB  - Autoimmune Addison's disease (AAD) is a complex disorder with several
      susceptibility loci. Variations in the NLRP1 (previously, NALP1) gene have
      recently been reported to confer risk for vitiligo and associated autoimmune
      conditions. We hypothesized that polymorphisms in this gene may affect
      susceptibility to AAD. The aim of this study was to analyze the associations of
      six NLRP1 single-nucleotide polymorphisms (SNPs) with AAD within a Polish cohort.
      The study comprised 101 AAD patients and 254 healthy control individuals.
      Genotyping was performed by polymerase chain reaction followed by restriction
      fragment length polymorphism and single strand conformation polymorphism methods.
      The minor allele of the coding SNP rs12150220 appeared significantly more
      frequently in AAD compared with healthy individuals (OR = 1.5, 95% CI, 1.08-2.08,
      p = 0.015). The distribution of genotypes also demonstrated significant
      differences. The frequency of high-risk genotype AA of rs12150220 SNP was
      significantly increased among AAD subjects versus controls (p = 0.006 and p =
      0.036, respectively; significant after Bonferroni correction), yielding an OR of
      2.96 (95% CI, 1.34-6.55). Likewise, the heterozygous genotype TA was observed
      more frequently in the patient group [OR = 3.09 (95% CI, 1.53-6.24), p = 0.001
      and p = 0.006 after Bonferroni correction]. In conclusion, this study confirms an
      association between the coding polymorphism in NLRP1 and AAD.

PMID- 20152875
TI  - Association analysis of MICA gene polymorphism and MICA-129 dimorphism with
      inflammatory bowel disease susceptibility in a Spanish population.
AB  - MICA is located at 46 kb centromeric of HLA-B, is highly polymorphic and
      interactions with NKG2D, its receptor on the surface of NK, Tgammadelta, and T
      CD8 lymphocytes. A variation at amino acid position 129 of the alpha2-heavy chain
      domain seems to categorize MICA alleles into strong and weak binder of NKG2D
      receptor, and thereby to influence effector cell function. Our aim was to study
      allele polymorphism of MICA and the functionally relevant dimorphism (129val/met)
      of MICA gene in inflammatory bowel disease (IBD) patients in our population. DNA
      was obtained from IBD patients (n = 88) and unrelated healthy Murcians (n = 154)
      and used to MICA genotyping using polymerase chain reaction-sequence-specific
      oligonucleotides. We did not find statistical differences in the distribution of
      MICA alleles between the IBD and control groups. However, we found a higher
      frequency of MICA-129met/met and a lower frequency of MICA-129val/met genotypes
      in IBD patients (mainly in ulcerative colitis) than in controls (pc = 0.02).
      These preliminary data could suggest a relevant role of MICA-129-val/met SNP
      (weak/strong binders of NKG2D receptor) in the pathogenesis of IBD.

PMID- 20152876
TI  - Human health risk assessment of pharmaceuticals in water: an uncertainty analysis
      for meprobamate, carbamazepine, and phenytoin.
AB  - This study presents a step-wise development of a quantitative pharmaceutical risk
      assessment (QPhRA, hereafter) framework, including Monte Carlo uncertainty
      analysis for meprobamate, carbamazepine, and phenytoin during (1) accidental
      exposures of stream water and fish consumption and (2) direct ingestion of
      finished drinking water for children and adults. Average hazard quotients of
      these pharmaceuticals (i.e., the ratio of values of chronic daily intake to
      acceptable daily intake) were found to lie between 1x10(-10) and 3x10(-5) and 99
      th percentile values of hazard quotients were found to be less than 1x10(-4) for
      both sub-populations, indicating no potential risks of adverse effects due to
      pharmaceuticals exposures. In addition, pharmaceutical concentrations were also
      observed to be lower than their respective calculated acceptable daily intake
      equivalent drinking water levels, indicating no potential human health risks. To
      the authors' knowledge, for the first time in QPhRA studies, this study has
      attempted to characterize and quantify effects of factors, such as considerations
      for sensitive sub-populations using subpopulation-specific toxic endpoints and
      use of pharmaceutical concentrations in stream and finished drinking waters on
      risk estimates. Acceptable daily intake was observed to be the primary
      contributor (>93% variance contribution) in the overall uncertainties of
      estimates of hazard quotients, followed by fish consumptions and pharmaceutical
      concentrations in water. Further research efforts are required to standardize use
      of acceptable daily intake values to reduce large variability in estimation of
      hazard quotients.

PMID- 20152877
TI  - N-Chloroamino acids mediate the action of hypochlorite on A549 lung cancer cells
      in culture.
AB  - Hypochlorous acid, a chlorinating and oxidative agent, has been reported to be
      implicated in many pathologies. Its markers were found under inflammatory
      conditions and, at least some of it reveals biological activity. Thus, in this
      paper we examined whether N-chloroamino acids may act as mediators of the action
      of hypochlorous acid in cell culture. N-Chloroamino acids were found to possess
      lower oxidative capacity than HOCl/OCl(-) just after addition to the growth
      medium. However, all the chlorocompounds studied were cytotoxic to A549 cells,
      induced a dose-dependent increase in the G(0)/G(1) fraction with simultaneous
      reduction in the G(2)/M fraction, collapse of the mitochondrial potential and
      caspase-dependent apoptosis. The content of cellular thiols decreased after 1-h
      incubation with the chlorocompounds studied. Although amino acids act as
      scavengers of hypochlorite in plasma, the chlorinated products formed stay
      reactive and the pattern of their action on cells in vitro is similar to that of
      hypochlorite.

PMID- 20152878
TI  - Heteromeric connexin 43/connexin 33 complex endocytosis: a connexin
      phosphorylation independent mechanism.
AB  - The role of gap junctions in proliferation, differentiation and apoptosis has
      been recently highlighted. Nevertheless, the molecular mechanisms that control
      these physiological events by acting on gap junction channels are still unknown.
      We have recently demonstrated that heteromeric gap junction plaques composed by
      Cx43 and Cx33 are unstable at the cell boundary and are rapidly internalized by
      endocytosis. In the present study, we analyze the phosphorylation status of Cx43
      in homomeric (Cx43/Cx43) and heteromeric (Cx33/Cx43) complexes and their
      association with the tyrosine kinase c-Src. Our data show that c-Src interaction
      and P2 phosphorylation of Cx43, which are essential for homomeric Cx43 complex
      endocytosis, were altered in the heteromeric Cx33/Cx43 complex: lack of
      association between Cx33 and activated c-Src and disappearance of the P2
      phosphorylated Cx43 isoform. The present findings demonstrate that the
      interaction of Cx33 with Cx43 within a same heteromeric complex may conduce to
      channel instability through alteration of the phosphorylation status of Cx43
      independently of the control of the c-Src kinase. The data described here
      emphasize a new mechanism of Cx43 internalization Src kinase-independent.

PMID- 20152879
TI  - Performance monitoring and error significance in patients with obsessive
      compulsive disorder.
AB  - Performance monitoring has been consistently found to be overactive in obsessive
      compulsive disorder (OCD). The present study examines whether performance
      monitoring in OCD is adjusted with error significance. Therefore, errors in a
      flanker task were followed by neutral (standard condition) or punishment
      feedbacks (punishment condition). In the standard condition patients had
      significantly larger error-related negativity (ERN) and correct-related
      negativity (CRN) ampliudes than controls. But, in the punishment condition groups
      did not differ in ERN and CRN amplitudes. While healthy controls showed an
      amplitude enhancement between standard and punishment condition, OCD patients
      showed no variation. In contrast, group differences were not found for the error
      positivity (Pe): both groups had larger Pe amplitudes in the punishment
      condition. Results confirm earlier findings of overactive error monitoring in
      OCD. The absence of a variation with error significance might indicate that OCD
      patients are unable to down-regulate their monitoring activity according to
      external requirements.

PMID- 20152880
TI  - The APOE-491 A/T promoter polymorphism effect on cognitive profile of Alzheimer's
      patients.
AB  - Alzheimer's Disease (AD) is a neurodegenerative disorder with a complex aetiology
      displayed by multiple pathogenic factors. The APOE varepsilon4 allele represents
      the only established genetic risk factor for sporadic AD; in addition, previous
      findings on three single nucleotide polymorphisms (SNPs) located on the APOE
      promoter region, have led to a growing interest in their potential role in AD
      pathogenesis. The -491 A/T promoter polymorphism has been the one most frequently
      shown to be associated with AD, as it influences the APOE coding region
      transcription. The aim of this study was to evaluate the possible effect of the 
      491 A/T polymorphism on the cognitive profile of sporadic AD patients with a
      disease severity ranging from mild to moderate. Our results showed that patients
      carrying the -491 AA genotype had poorer cognitive performances than the -491 AT
      ones, statistically significant in demanding tests of visual attention,
      especially for the late-onset AD (LOAD). No further differences on cognitive
      profile were observed when stratifying AA and AT patients according to their APOE
      genotype. These results suggest a possible functional effect of the -491 A/T
      promoter on the neuropsychological performances of AD. This role seems to be
      independent of APOE genotype. In fact the effect of -491 A/T occurs predominantly
      on attention while the APOE varepsilon4 allele mainly affects memory
      performances. According to the biological effect exerted on APOE transcription,
      the -491 A/T polymorphism could be considered a disease modifier more than a risk
      factor for sporadic AD.

PMID- 20152881
TI  - Neuroprotective effects of cyanidin 3-O-glucopyranoside on amyloid beta (25-35)
      oligomer-induced toxicity.
AB  - Recent studies suggest that the oligomers of short amyloid beta (Abeta) peptides
      such as Abeta(25-35) as well as full-length Abeta peptides (i.e. Abeta(1-40) and
      Abeta(1-42) peptides) are responsible for synaptic dysfunction and/or neuronal
      loss in Alzheimer's disease (AD). Among antioxidant phytochemicals derived from
      fruit and vegetables, cyanidin 3-O-glucoside (Cy-3G) has recently gained
      attention for its neuroprotective properties. In this in vitro study, we
      demonstrated that Cy-3G can inhibit Abeta(25-35) spontaneous aggregation into
      oligomers and their neurotoxicity in human neuronal SH-SY5Y cells. In particular,
      the pre- and co-treatment of SH-SY5Y cells with Cy-3G reduced the neuronal death,
      in terms of apoptosis and necrosis, elicited by Abeta(25-35) oligomers. Cy-3G
      also shows the interesting ability to prevent the early events leading to
      neuronal death such as the Abeta(25-35) oligomer binding to plasma membrane and
      the subsequent membrane integrity loss. Taken together, these findings suggest
      that Cy-3G may be considered a phytochemical with neuroprotective properties
      useful in finding potential drug or food supplements for the therapy of AD.

PMID- 20152882
TI  - Visuotactile empathy within the primary somatosensory cortex revealed by short
      latency afferent inhibition.
AB  - Intersubjectivity entails the taking of another's perspective in order to
      understand their experience of the world. This perspective taking capacity
      extends to the intra-individual sharing of tactile experience. Previous studies
      have shown modulation of motor cortex excitability in response to the observation
      of aversive tactile stimulation to the hand of another person. Here we used
      transcranial magnetic stimulation (TMS) and peripheral stimulation to induce a
      short-latency afferent inhibition (SAI) effect, which we then sought to modulate
      via observation of non-noxious tactile stimulation to the hand of a model. Side
      congruency between the observed (model) and the recorded (participant) hand
      induced an increase of SAI and this effect was found to hold for motor-evoked
      potentials (MEPs) recorded from both left and right hands. Inhibition was not
      found with MEPs evoked using unconditioned pulses of TMS. These results
      demonstrate a sensorimotor response to observed non-noxious stimulation and
      suggest an empathic matching system for the tactile experiences of others.

PMID- 20152883
TI  - Eugenol modifies the excitability of rat sciatic nerve and superior cervical
      ganglion neurons.
AB  - Eugenol is a phenylpropene obtained from the essential oils of plants such as
      clove and basil which has ample use in dentistry. Eugenol possesses analgesic
      effects that may be related to the inhibition of voltage-dependent Na+ channels
      and/or to the activation of TRPV1 receptors or both. In the present study,
      electrophysiological parameters were taken from the compound action potentials of
      the isolated rat sciatic nerve and from neurons of the superior cervical ganglion
      (SCG) impaled with sharp microelectrodes under current-clamp conditions. In the
      isolated rat sciatic nerve, eugenol inhibited the compound action potential in a
      concentration-dependent manner. Action potentials recorded from SCG neurons were
      inhibited by eugenol with an IC(50) of 0.31 mM. At high concentrations (2 mM),
      during brief applications, eugenol caused significant action potential blockade
      while it did not interfere with the resting membrane potential or the membrane
      input resistance. Surprisingly, however, at low eugenol concentrations (0.6 mM),
      during long time applications, a reversible reduction (by about 50%) in the input
      membrane resistance was observed, suggesting the possible involvement of a
      secondary delayed effect of eugenol to reduce neuronal excitability.

PMID- 20152884
TI  - The effect of hyperpolarizing inputs on the dynamics of a bursting pacemaker
      neuron model in the pre-Botzinger complex.
AB  - The pre-Botzinger complex (pre-BotC), a subregion of the ventrolateral medulla
      involved in respiratory rhythm generation, contains intrinsically bursting
      pacemaker neurons. A previous study proposed Hodgkin-Huxley type minimal models
      for pacemaker neurons and predicted the effect of a hyperpolarizing input on the
      dynamics of a model under certain conditions. In this model, bursting is
      explained by the dynamics of a persistent sodium current. In the present study,
      the effect of a hyperpolarizing input on the dynamics of a model was investigated
      under variable conditions. It was observed that immediately after an input of
      sufficient intensity and duration, an increase in the maximal value of the gating
      variable h of a persistent sodium current was brought about by a decrease in the
      timing of the hyperpolarizing input. This corresponds to an observation that
      immediately after the input, a monotonic increase in the number of spikes in the
      neuron model was brought about by a decrease in the timing of the hyperpolarizing
      input. In addition, the dependency of burst duration immediately after the input
      on the timing of the hyperpolarizing input varied depending on the condition of
      input. The present study is the first to elucidate that the influence of
      hyperpolarizing inputs on the number of spikes within a burst in a pacemaker
      neuron model in the pre-BotC is dependent on the timing of the hyperpolarizing
      input and to clarify the possible mechanism of this influence, thereby
      facilitating a detailed understanding of the dynamics of a pacemaker neuron model
      in the pre-BotC.

PMID- 20152885
TI  - Preliminary study on the effect of trauma-induced secondary cellular hypoxia in
      brain injury.
AB  - Secondary cerebral hypoxia has recently been shown to play an important role in
      the outcome of patients suffering from traumatic brain injury (TBI). However, the
      precise mechanisms underlying secondary cerebral hypoxia are complex and
      interrelated. In this study, we investigate the effect of hypoxia within a rat
      model of trauma-induced late cerebral cortex injury. Using the hypoxia marker
      pimonidazole, we verified and isolated areas of the cortex that had suffered
      hypoxic damage. Using subsequent reverse-transcriptase PCR analyses, we found
      that the expressions of both transforming growth factor beta1 (TGF-beta1) and
      hypoxia-inducible factor-1alpha (HIF-1alpha) increased significantly under
      hypoxic conditions induced by TBI compared with uninjured control animals. In
      addition, the maximum mRNA expression of TGF-beta1 and HIF-1alpha was found at 3
      days and 12h after TBI, respectively. Our data suggest that secondary cerebral
      hypoxia injury involves various cytokines including TGF-beta1 and HIF-1alpha.
      Furthermore, upon immunohistochemical analysis, both TGF-beta1 and HIF-1alpha
      expression were almost localized in the same types of cells by using
      immunohistochemical study. These results may have important implications in the
      understanding of trauma-induced secondary cerebral hypoxia injury.

PMID- 20152886
TI  - Interaction among the components of multiple auditory steady-state responses:
      enhancement in tinnitus patients, inhibition in controls.
AB  - Amplitude and phase of steady-state signals recorded in response to amplitude
      modulated (AM) sine tones vary over time, suggesting that the steady-state
      response (SSR) reflects not only stimulus input but also its interaction with
      other input streams or internally generated signals. Alterations of the
      interaction between simultaneous SSRs associated with tinnitus were studied by
      recording the magnetic field evoked by AM-tones with one of three carrier and one
      of three modulation frequencies. Single AM-tones were presented in single
      presentation mode and superpositions of three AM-tones differing in carrier and
      modulation frequency in multiple presentation mode. Modulation frequency-specific
      SSR components were recovered by bandpass filtering. Compared with single mode,
      in multiple mode SSR amplitude was reduced in healthy controls, but increased in
      tinnitus patients. Thus, while in controls multiple response components seem to
      reciprocally inhibit one another, in tinnitus reciprocal facilitation seems to
      predominate. Reciprocal inhibition was unrelated to the phase coherence among SSR
      components, but was correlated with the frequency of phase slips, indicating that
      the lateral interaction among SSR components acts in a quasi-paroxysmal manner
      and manifests itself in terms of a random train of phase reset events. Phase
      slips were more frequent in patients than controls both in single and multiple
      mode. Together, these findings indicate that lateral or surround inhibition of
      single units in auditory cortex is reduced and suggest that in-field inhibition
      is increased in tinnitus.

PMID- 20152887
TI  - Clinical and genetic evaluation of a family showing both autism and epilepsy.
AB  - Autism is a strong genetic disorder, with an estimated heritability greater than
      90%. Nonetheless, its specific genetic aetiology remains largely unknown. Autism
      is associated with epilepsy in early childhood and epilepsy occurs in 10-30% of
      individuals with autism. Here we report the case of a woman affected by a severe
      epileptic disorder with an onset at 14 years old. She is affected by a
      cryptogenetic focal epilepsy with complex partial (psychomotor) and secondarily
      generalized tonic-clonic seizures, which are drug resistant. The woman is married
      to a healthy man and has six children: two girls are healthy, a girl and two boys
      are affected by autism while one boy shows partial seizures. The three children
      with autism show moderate mental retardation and an EEG with no epileptiform
      alterations. The child with epileptic seizures shows an asymmetric EEG that is
      not necessarily pathological. In this family, no chromosomal rearrangements were
      detected by means of classical cytogenetic analyses. The presence of FRAXA
      alterations and of microdeletions of the 15q11-q13 chromosome region were also
      excluded. A genome-wide linkage analysis using microsatellite markers revealed
      several chromosome regions as possible susceptibility loci.

PMID- 20152888
TI  - The proconvulsant effects of leptin on glutamate receptor-mediated seizures in
      mice.
AB  - The metabolic-related hormone, leptin has been suggested for clinical use as an
      anticonvulsant based upon data generated from in vitro and in vivo non-human
      studies. However, a number of other non-human experiments have demonstrated
      proconvulsant activity for leptin. The current study investigated potential pro-
      and anticonvulsant effects of leptin during exposure to either glutamate (the
      major endogenous excitatory neurotransmitter) or three subtype-selective
      glutamate receptor agonists (N-methyl-d-aspartic acid [NMDA], alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], and kainate). Male C57BL/6JRj
      mice were pretreated with leptin (0.1-10mg/kg, i.p.) and then administered doses
      of the glutamate receptor agonists (i.p.) that had been previously shown to
      result in clonic convulsions in approximately half of the animals tested. Leptin
      had no clear convulsant-related effects with either glutamate or AMPA, but it
      exhibited dose-related, proconvulsant activity (decreased latency to first
      occurrence of various convulsion-related signs, and increased percentage of
      animals exhibiting such signs) with both NMDA and kainate. The proconvulsant
      effects of leptin observed during the current study suggest that a cautious
      approach should be taken when administering leptin to individuals who may be
      prone to seizures.

PMID- 20152889
TI  - Extinction, relapse, and behavioral momentum.
AB  - Previous experiments on behavioral momentum have shown that relative resistance
      to extinction of operant behavior in the presence of a discriminative stimulus
      depends upon the baseline rate or magnitude of reinforcement associated with that
      stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have
      shown that relapse of operant behavior in reinstatement, resurgence, and context
      renewal preparations also is a function of baseline stimulus-reinforcer
      relations. In this paper we present new data examining the role of baseline
      stimulus-reinforcer relations on resistance to extinction and relapse using a
      variety of baseline training conditions and relapse operations. Furthermore, we
      evaluate the adequacy of a behavioral momentum based model in accounting for the
      results. The model suggests that relapse occurs as a result of a decrease in the
      disruptive impact of extinction precipitated by a change in circumstances
      associated with extinction, and that the degree of relapse is a function of the
      pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across
      experiments, relative resistance to extinction and relapse were greater in the
      presence of stimuli associated with more favorable conditions of reinforcement
      and were positively related to one another. In addition, the model did a good job
      in accounting for these effects. Thus, behavioral momentum theory may provide a
      useful quantitative approach for characterizing how differential reinforcement
      conditions contribute to relapse of operant behavior.

PMID- 20152890
TI  - Anatomy of deception: a behavioral contingency analysis.
AB  - Deception, a basic and pervasive biological phenomenon, takes many forms,
      variously referred to as mimicry, trickery, seduction, pretense, feigning,
      masquerading, impersonation, distraction, or false promises, and these share
      certain common distinguishing behavioral elements that permit them to be
      classified into categories. A symbolic language for the codification and analysis
      of behavioral contingencies shows that all instances of deception are based on a
      misperception, misprediction, non-perception, or non-prediction by the deceived
      party, and can be further categorized based on features of the contingencies that
      define them. Instances of particular interest are those in which a deceiving
      party predicts (and in that sense "intends") the deception. In those instances,
      the effect of the deception is usually to the deceiving party's benefit and to
      the deceived party's detriment. In economics, finance, business, military
      operations, public affairs, education, and everyday social interaction, deception
      takes numerous forms. Special forms, usually involving obfuscation, concealment,
      counterfeiting, and misrepresentation, occur in certain prevalent types of
      property transfer, including securitization, the creation of derivatives, and
      various types of Ponzi schemes. Such property transfers tend to be driven by
      opportunities for deception. They all involve blurring and clouding of the
      contingencies that defined the transferred properties, thus permitting their
      obfuscation.

PMID- 20152891
TI  - The effect of Hamming distances in a computational model of selection by
      consequences.
AB  - McDowell (2004) instantiated the Darwinian principles of selection,
      recombination, and mutation in a computational model of selection by
      consequences. The model has been tested under a variety of conditions and the
      outcome is quantitatively indistinguishable from that displayed by live
      organisms. The computational model animates a virtual organism with a repertoire
      of 100 behaviors, selected from the integers from 0 to 1023, where the
      corresponding binary representations constitute the behavior's genotypes. Using
      strings of binary digits raises the specific problem of Hamming distances: the
      number of bits that must be changed from 1 to 0 or from 0 to 1 in order to obtain
      another string of equal length. McDowell hypothesized that the Hamming distance
      may be computationally equivalent to the changeover delay used in experiments
      with live organisms. The results of the present experiments confirmed this
      hypothesis and revealed a robust rule about the effects of Hamming distances
      within the model, namely, in order to obtain good matching, the difference
      between the Hamming distance that separates the target classes and the largest
      Hamming distance comprised within a class must be equal to or larger than three.

PMID- 20152892
TI  - Anti-secretory, anti-inflammatory and anti-Helicobacter pylori activities of
      several fractions isolated from Piper carpunya Ruiz & Pav.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Piper carpunya Ruiz & Pav. (syn
      Piper lenticellosum C.D.C.) (Piperaceae), are widely used in folk medicine in
      tropical and subtropical countries of South America as an anti-inflammatory, anti
      ulcer, anti-diarrheal and anti-parasitical remedy as well as an ailment for skin
      irritations. AIMS OF THE STUDY: To study the anti-inflammatory, anti-secretory
      and anti-Helicobacter pylori activities of different fractions isolated from an
      ethanolic extract of the leaves of Piper carpunya, in order to provide evidence
      for the use of this plant as an anti-ulcer remedy. Moreover, to isolate the main
      compounds of the extract and relate their biological activity to the experimental
      results obtained with the fractions. MATERIALS AND METHODS: Sixteen fractions
      were obtained from the ethanolic extract (F I-XVI) and 16 pure compounds were
      isolated and identified from these fractions. We studied the effects of the
      fractions (0.1-400microg/mL) on the release of myeloperoxidase (MPO) enzyme from
      rat peritoneal leukocytes, on rabbit gastric microsomal H(+), K(+)-ATPase
      activity and anti-Helicobacter pylori anti-microbial activity using the
      microdilution method (MM). The main compounds contained in the fractions were
      isolated and identified by (1)H- and (13)C NMR spectra analysis and comparison
      with the literature data. RESULTS: Eight fractions showed inhibition of MPO
      enzyme (F I-IV, X, XII, XIV and XV). The highest inhibition was observed with F
      XIV (50microg/mL, 60.9%, p<0.001). F X and XII were the most active ones,
      inhibiting the gastric H(+), K(+)-ATPase activity with IC(50) values equal to
      22.3microg/mL and 28.1microg/mL, respectively. All fractions, except F XV,
      presented detectable anti-Helicobacter pylori activity, with a diameter of
      inhibition zones ranging from 11mm up to 50mm. The best anti-Helicobacter pylori
      activity was obtained with F III and V. Both fractions killed Helicobacter pylori
      with lowest concentration values, about 6.25mug/mL. Sixteen pure compounds were
      isolated, five of them are flavonoids that possess strong anti-oxidant and free
      radical scavenging activity, e.g. vitexin, isovitexin, and
      rhamnopyranosylvitexin. Terpenoids like sitosterol, stigmasterol and phytol,
      which have shown gastroprotective activity, and dihydrochalcones, like
      asebogenin, with anti-bacterial activity, were also isolated. Furthermore, the
      rare neolignan 1, that is a DNA polymerase beta lyase inhibitor, and (6S, 9S)
      roseoside, that shows strong anti-bacterial activity, were isolated, for the
      first time, from the genus Piper. CONCLUSIONS: We suggest that the flavonoids
      isolated from F I and II (vitexin, isovitexin, rhamnopyranosylvitexin and
      isoembigenin) contribute to the anti-MPO activity, as well as to their anti
      Helicobacter pylori activity. These flavonoids may also be responsible for the
      important inhibition of H(+), K(+)-ATPase activity. Also the phytosterols and
      phytol obtained from F XIV and XV could be involved in these gastroprotective
      activities. These results encourage us to continue phytochemical studies on these
      fractions in order to obtain full scientific validation for this species.

PMID- 20152893
TI  - Antinociceptive activities of the methanol extract of the bulbs of Dioscorea
      bulbifera L. var sativa in mice is dependent of NO-cGMP-ATP-sensitive-K(+)
      channel activation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea bulbifera var sativa is a medicinal
      plant commonly used in Cameroonian traditional medicine to treat pain and
      inflammation. AIM: The present work evaluated the effects of the methanol extract
      of the bulbs of Dioscorea bulbifera in inflammatory and neuropathic models of
      pain and further investigated its possible mechanism of action. MATERIALS AND
      METHODS: The effects of Dioscorea bulbifera administered orally at the doses of
      250 and 500mg/kg were tested in mechanical hypernociception induced by
      intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA),
      lipopolysaccharides (LPS) or prostaglandin-E(2) (PGE(2)), as well as in partial
      ligation sciatic nerve (PLSN), nociception induced by capsaicin and thermal
      hyperalgesia induced by i.pl. injection of CFA. The therapeutic effects of
      Dioscorea bulbifera on PGE(2)-induced hyperalgesia were evaluated in the absence
      and in the presence of l-NAME, an inhibitor of nitric oxide synthase (NOS) and
      glibenclamide, an inhibitor of ATP-sensitive potassium channels. RESULTS: The
      extract showed significant antinociceptive effects in persistent pain induced by
      CFA and on neuropathic pain induced by PLSN. The effects of Dioscorea bulbifera
      persisted for 5 days after two administrations in CFA-induced hypernociception.
      Dioscorea bulbifera significantly inhibited acute LPS-induced pain but failed to
      reduce thermal hypernociception and capsaicin-induced spontaneous nociception.
      The antinociceptive effects of this plant extract in PGE(2) model was antagonized
      by either l-NAME or glibenclamide. CONCLUSION: Present demonstrate the
      antinociceptive activities of Dioscorea bulbifera both in inflammatory and
      neuropathic models of pain and these effects may result, at least partially, from
      its ability to activate the NO-cGMP-ATP-sensitive potassium channels pathway.

PMID- 20152894
TI  - Production of heterologous proteins in plants: strategies for optimal expression.
AB  - Plants are a promising expression system for the production of heterologous
      proteins, especially therapeutic proteins. Currently the majority of therapeutic
      proteins are produced in mammalian cell lines or bacteria. In a few cases
      insects, yeast and fungi have been developed for production of human proteins.
      However, these expression systems have limitations in terms of suitability, cost,
      scalability, purification and post-translational modifications. Therefore,
      alternative expression systems are being developed in transgenic animals and
      transgenic plants. Transgenic plants could provide an attractive alternative in
      terms of low production cost and lower capital investment in infrastructure, and
      with appropriate post-translational modifications. The potential of plants as an
      expression host has not been capitalized, primarily due to lower level of
      expression of transgenes in plants. The present review will evaluate the rate
      limiting steps of plant expression systems and suggest strategies to optimize
      protein expression at each of the steps: gene integration, transcription,
      translation and protein accumulation.

PMID- 20152895
TI  - In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant
      properties of pterostilbene isolated from Pterocarpus marsupium.
AB  - Pterostilbene, a dimethyl ester derivative of resveratrol, may act as an
      cytotoxic and hence as an anti-cancer agent. The present study was conducted to
      test the anti-cancer activity of pterostilbene purified from Pterocarpus
      marsupium on breast (MCF-7) and prostate (PC3) cancer cell lines. The purified
      pterostilbene was found to cause apoptosis in both the cell lines, which was
      marked by DNA fragmentation, formation of apoptotic bodies and membrane
      distortions. Apoptosis probably was due to the production of reactive oxygen
      species in MCF-7 and nitric oxide over production in PC3 cells. Even the drug
      detoxifying anti-oxidant enzymes could not nullify the effect of pterostilbene as
      required by the cancer cells for survival. Pterostilbene was found to inhibit the
      cell proliferating factors like Akt, Bcl-2 and induced the mitochondrial
      apoptotic signals like Bax, and the series of caspases. It also inhibited Matrix
      metalloproteinase 9 (MMP9) and alpha-methylacyl-CoA recemase (AMACR), two very
      well known metastasis inducers. In conclusion, pterostilbene has multiple target
      sites to induce apoptosis. Hence, after proper validation it can be used as a
      potential agent for the cure of breast and prostate cancer.

PMID- 20152896
TI  - Manganese-mediated up-regulation of HIF-1alpha protein in Hep2 human laryngeal
      epithelial cells via activation of the family of MAPKs.
AB  - High exposure of manganese is believed to be a risk factor for respiratory
      diseases. Evidence suggests that overexpression of HIF-1alpha transcription
      factor is linked to pulmonary inflammation and vascular change. In this study, we
      investigated the effect of manganese-chloride (manganese) on expression and
      activity of HIF-1alpha in various human airway cells, including Hep2 (laryngeal),
      H292 (bronchial), and A549 (lung). Profoundly, while manganese treatment led to
      low or little effect on induction of HIF-1alpha protein in H292 or A549 cells, it
      strongly induced HIF-1alpha protein expression in Hep2 cells. Mn treatment,
      however, did not induce HIF-1alpha mRNA expression in Hep2 cells. Luciferase
      experiments further demonstrated that manganese treatment increased the HRE
      driven luciferase activity, suggesting that the induced HIF-1 is functional.
      Interestingly, manganese treatment also caused activation of p38 MAPK, JNK-1/2,
      ERK-1/2, and ATF-2, but not of PKB or NF-kappaB in Hep2 cells. Importantly, the
      manganese-mediated expression and activity of HIF-1alpha protein were largely
      blocked by treatment with the inhibitor of p38 MAPK (SB203580), JNK-1/2
      (SP600125), or ERK-1/2 (PD98059), suggesting roles of these MAPKs in the
      manganese-induced HIF-1alpha protein expression and activity. Moreover, treatment
      with SP600125 or SB203580, but not PD98059, had partial inhibitory effects on the
      stability of HIF-1alpha protein induced by manganese, suggesting that p38 MAPK
      and JNK-1/2 also contribute to the Mn-mediated HIF-1alpha protein stability.
      These results suggest that manganese is able to up-regulate HIF-1alpha at the
      protein level in Hep2 cells and the up-regulation is largely dependent of
      activities of the family of MAPKs.

PMID- 20152897
TI  - Differential induction of MAP kinase signalling pathways by cadmium in primary
      cultures of mouse embryo limb bud cells.
AB  - While it is well accepted that mammalian embryos may develop abnormally in
      response to harmful environmental stresses, the molecular changes that embryonic
      cells undergo are not always clear. In the present study we examined the
      induction of mitogen-activated protein kinase (MAPK) pathways by cadmium chloride
      (CdCl(2)) in micromass cultures of limb bud cells from day 11 BALB/c mouse
      embryos. CdCl(2) exposure was found to cause a marked reduction in both cell
      survival and differentiation in these cultures. To study stress signalling
      pathways, cells were lysed and were examined for the phosphorylation of three
      MAPKs. It was shown that 4 microM CdCl(2) treatment of limb bud cells caused the
      phosphorylation of c-Jun N-terminal kinase (JNK), but not p38 or extracellular
      signal-regulated kinase (ERK), over a 120min period. The results indicate a
      specific activation of the JNK pathway in response to CdCl(2)-induced toxicity in
      mouse limb bud cells.

PMID- 20152898
TI  - Arylsulfatase B regulates interaction of chondroitin-4-sulfate and kininogen in
      renal epithelial cells.
AB  - The enzyme arylsulfatase B (N-acetylgalactosamine 4-sulfatase; ASB; ARSB), which
      removes 4-sulfate groups from the nonreducing end of chondroitin-4-sulfate
      (C4S;CSA) and dermatan sulfate, has cellular effects, beyond those associated
      with the lysosomal storage disease mucopolysaccharidosis VI. Previously, reduced
      ASB activity was reported in cystic fibrosis patients and in malignant human
      mammary epithelial cell lines in tissue culture compared to normal cells. ASB
      silencing and overexpression were associated with alterations in syndecan-1 and
      decorin expression in MCF-7 cells and in IL-8 secretion in human bronchial
      epithelial cells. In this report, we present the role of ASB in the regulation of
      the kininogen-bradykinin axis owing to its effect on chondroitin-4-sulfation and
      the interaction of C4S with kininogen. Silencing or overexpression of ASB in
      normal rat kidney epithelial cells in tissue culture modified the content of
      total sulfated glycosaminoglycans (sGAGs), C4S, kininogen, and bradykinin in
      spent media and cell lysates. Treatment of the cultured cells with chondroitinase
      ABC also increased the secretion of bradykinin into the spent media and reduced
      the C4S-associated kininogen. When ASB was overexpressed, the cellular kininogen
      that associated with C4S declined, suggesting a vital role for chondroitin-4
      sulfation in regulating the kininogen-C4S interaction. These findings suggest
      that ASB, owing to its effect on chondroitin-4-sulfation, may impact on the
      kininogen-bradykinin axis and, thereby, may influence blood pressure. Because ASB
      activity is influenced by several ions, including chloride and phosphate, ASB
      activity may provide a link between salt responsiveness and the bradykinin
      associated mechanism of blood pressure regulation.

PMID- 20152899
TI  - Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are
      bioequivalent.
AB  - AIM: The pharmacokinetic profiles of the two commercially available transdermal
      fentanyl patches Matrifen (100 microg/h) and Durogesic DTrans (100 microg/h),
      used to manage severe chronic pain, were compared regarding their systemic
      exposure, rate of absorption, and safety. METHODS: Transdermal matrix fentanyl
      patches [Matrifen or Durogesic DTrans (100 microg/h)] were applied for 72 h to 30
      healthy male subjects in a randomized, four-period (two replicated treatment
      sequences), crossover study; 28 subjects completed the study. The pharmacokinetic
      parameters of fentanyl were determined for 144 h after application using plasma
      samples. Safety of the patches (adverse events) and performance (adhesion, skin
      irritation, residual fentanyl content in the patch) were evaluated. RESULTS: The
      plasma concentration-time curves of Matrifen (Test) and Durogesic DTrans
      (Reference) were similar. The geometric least square means of the Test/Reference
      ratio (90% confidence intervals [CI]) were within the range of 80-125%,
      demonstrating bioequivalence of Matrifen and Durogesic DTrans: AUC(0-tlast) 92.5
      (CI 88.7-96.4), AUC(0-inf) 91.7 (CI 88.0-95.7), and C(max) 98.3 (CI 92.9-104.1).
      After 72 h application, Matrifen had a more efficient utilization of fentanyl
      (mean+/-SD 82.3+/-9.43%) than Durogesic DTrans (52.3+/-12.8%), with substantially
      lower residual fentanyl in patch after use. The pharmacokinetic parameters showed
      lower intra- and inter-subject variability for Matrifen than for Durogesic DTrans
      patch. CONCLUSIONS: Despite different technologies, the transdermal fentanyl
      patches Matrifen and Durogesic DTrans are bioequivalent. Compared with Durogesic
      DTrans, the Matrifen patch had lower initial and lower residual fentanyl content,
      as well as lower intra- and inter-subject variability, allowing reproducible drug
      delivery and reliable analgesia.

PMID- 20152900
TI  - 1alpha-hydroxylase and innate immune responses to 25-hydroxyvitamin D in colonic
      cell lines.
AB  - Vitamin D-insufficiency is a prevalent condition in populations throughout the
      world, with low serum levels of 25-hydroxyvitamin D (25OHD) linked to a variety
      of human health concerns including cancer, autoimmune disease and infection.
      Current data suggest that 25OHD action involves localized extra-renal conversion
      to 1,25-dihydroxyvitamin D (1,25(OH)2D) via tissue-specific expression of the
      enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase). In cells such
      as macrophages, expression of 1alpha-hydroxylase is intimately associated with
      toll-like receptor (TLR) recognition of pathogens. However, this mechanism may
      not be exclusive to extra-renal generation of 1,25(OH)2D. To investigate the
      relationship between TLR-mediated pathogen recognition and vitamin D-induced
      antibacterial activity, intracrine responses to 25OHD metabolism were explored in
      vitro using the established colonic cell lines Caco-2 and Caco-2 clone BBe.
      Analysis of antibacterial factors such as cathelicidin (LL37) and beta-defensin-4
      (DEFB4) was carried out following co-treatment with TLR ligands. Data indicate
      that, unlike macrophages, Caco-2 and BBe colonic cell lines are unresponsive to
      TLR-induced 1alpha-hydroxylase. Alternative activators of 1alpha-hydroxylase such
      as transforming growth factor beta were also ineffective at priming intracrine
      responses to 25OHD. Thus, in common with other barrier sites such as the skin or
      placenta, colonic epithelial cells may require specific factors to initiate
      intracrine responses to vitamin D.

PMID- 20152901
TI  - Kinetic and structural characterization of human mortalin.
AB  - Human mortalin is an Hsp70 chaperone that has been implicated in cancer,
      Alzheimer's and Parkinson's disease, and involvement has been suggested in
      cellular iron-sulfur cluster biosynthesis. However, study of this important human
      chaperone has been hampered by a lack of active material sufficient for
      biochemical characterization. Herein, we report the successful purification and
      characterization of recombinant human mortalin in Escherichia coli. The
      recombinant protein was expressed in the form of inclusion bodies and purified by
      Ni-NTA affinity chromatography. The subsequently refolded protein was confirmed
      to be active by its ATPase activity, a characteristic blue-shift in the
      fluorescence emission maximum following the addition of ATP, and its ability to
      bind to a likely physiological substrate. Single turnover kinetic experiments of
      mortalin were performed and compared with another Hsp70 chaperone,
      Thermotogamaritima DnaK; with each exhibiting slow ATP turnover rates. Secondary
      structures for both chaperones were similar by circular dichroism criteria. This
      work describes an approach to functional expression of human mortalin that
      provides sufficient material for detailed structure-function studies of this
      important Hsp70 chaperone.

PMID- 20152902
TI  - Escherichia coli expression, refolding and characterization of human laforin.
AB  - Laforin is a unique human dual-specificity phosphatase as it contains an amino
      terminal carbohydrate binding module (CBM). Laforin gene mutations lead to Lafora
      disease, a progressive myoclonus epilepsy with an early fatal issue. Previous
      attempts to produce recombinant laforin faced various difficulties, namely the
      appearance of protein inclusion bodies, the contamination with bacterial proteins
      and a high tendency of the protein to aggregate, despite the use of fusion tags
      to improve solubility and ease the purification process. In this work, we have
      expressed human laforin in Escherichia coli in the form of inclusion bodies
      devoid of any fusion tags. After a rapid dilution refolding step, the protein was
      purified by two chromatographic steps, yielding 5-7mg of purified protein per
      liter of bacterial culture. The purified protein was shown to have the kinetic
      characteristics of a dual-specificity phosphatase, and a functional carbohydrate
      binding module. With this protocol, we were able for the first time, to produce
      and purify laforin without fusion tags in the amounts traditionally needed for
      the crystallographic structural studies paving the way to the understanding of
      the molecular mechanisms of laforin activity and to the development of novel
      therapies for Lafora disease.

PMID- 20152903
TI  - Fluorescence Detection of Heavy Atom Labeling (FD-HAL): a rapid method for
      identifying covalently modified cysteine residues by phasing atoms.
AB  - Membrane protein crystallography frequently stalls at the phase determination
      stage due to poor crystal diffraction and the inability to identify heavy atom
      derivatization prior to data collection. Thus, a majority of time, effort and
      resources are invested preparing potential derivatized crystals for synchrotron
      data collection and analysis without knowledge of heavy atom labeling. To remove
      this uncertainty, we introduce Fluorescence Detection of Heavy Atom Labeling (FD
      HAL) using tetramethylrhodamine-5-maleimide (a fluorescent maleimide compound) to
      monitor in-gel cysteine residue accessibility and ascertain covalent modification
      by mercury, platinum and gold compounds. We have tested this technique on three
      integral membrane proteins (LacY, vSGLT and mVDAC1) and can quickly assess the
      optimal concentrations, time and heavy atom compound to derivatize free cysteine
      residues in order to facilitate crystal phasing. This, in conjunction with
      cysteine scanning for incorporating heavy atoms at strategic positions, is a
      useful tool that will considerably assist in phasing membrane protein structures.

PMID- 20152904
TI  - Differentially expressed genes following persistent infection with infectious
      pancreatic necrosis virus in vitro and in vivo.
AB  - The mechanisms of viral persistence of infectious pancreatic necrosis virus
      (IPNV) are not well understood. In this study we have used a model of IPNV
      persistently infected CHSE (Chinook salmon embryonic) cells as correlate of
      persistent infection in fish focusing on differentially expressed genes using
      subtractive hybridization (SSH). Selected genes were also analyzed by
      quantitative real-time PCR (qPCR) in persistently infected parr of Atlantic
      salmon. Persistent infection was established by growing CHSE cells surviving an
      IPNV infection. Infection in rescued cells was non-lytic with a virus yield of
      10(3)-10(5) TCID(50)/ml of supernatant, resembling what can be found during a
      persistent infection in vivo. By comparing gene expression in persistently
      infected cell vs. non-infected cells we found an upregulation of genes involved
      in direct interaction or degradation of viral proteins, proteasome activating
      subunit 3, and of ATRX (X-linked alpha-thalassemia/mental retardation syndrome),
      a transcription repressor, which may indicate a repression of viral replication
      through reduced transcription. Further ephrin B1 (signal-transduction group) was
      found strongly up-regulated, and receptors for various ephrins are used for cell
      interaction and as entry points for other viruses in higher vertebrates.
      Endonuclease/reverse transcriptase 1 (RVT1) was also found highly up-regulated in
      persistently infected cells. The comparison of persistently infected cells to in
      vivo infected fish showed that the expression profiles found in CHSE cells give
      corresponding results for selected genes, as ATRX, ephrin B1 and RVT-1. We
      observed similar results by use of two independent methods (SSH and qPCR) for 8
      out of 15 genes analyzed and the transcript profile of persistently IPNV-infected
      cells involve upregulation of genes encoding proteins involved in viral protein
      degradation and translation inhibition. The understanding is that this may
      contribute to keep the number of virus particles low during viral persistence.

PMID- 20152905
TI  - Cloning and analysis of a ferritin subunit from turbot (Scophthalmus maximus).
AB  - Ferritin is an evolutionarily conserved protein that plays an important role in
      iron storage and detoxification. In this study, the gene encoding a ferritin H
      subunit homologue (SmFer1) was cloned from turbot (Scophthalmus maximus) and
      analyzed at the expression and functional levels. The open reading frame of
      SmFer1 is 534 bp and preceded by a 5'-untranslated region that contains a
      putative Iron Regulatory Element (IRE). The deduced amino acid sequence of SmFer1
      shares extensive sequence identities with the H ferritins of a number of fish
      species and contains the ferroxidase center that is preserved in ferritin H
      subunits. Examination of tissue specific expression indicated that SmFer1
      expression was most abundant in muscle, liver, and blood. Experimental infection
      with bacterial pathogens induced significant induction of SmFer1; however, the
      magnitudes of induction effected by Gram-negative pathogens were much higher than
      that induced by Gram-positive pathogen. Consistently, lipopolysaccharide (LPS)
      challenge drastically augmented SmFer1 expression. In addition to bacterial
      pathogens and LPS, poly(I:C) also induced a strong but transient induction of
      SmFer1 which differs in profile from those induced by bacterial pathogens. In
      vitro iron-chelating analysis showed that recombinant SmFer1 purified from
      Escherichia coli was able to bind ferrous iron in a concentration-dependent
      manner. To examine whether SmFer1, with its iron-chelating capacity, could have
      any effect on the infection of bacterial pathogens, purified recombinant SmFer1
      was subjected to bacteriostatic analysis and proved to be able to inhibit the
      growth of the fish pathogen Listonella anguillarum which enhanced SmFer1
      expression upon infection. Taken together, these results suggest that SmFer1 is
      likely to play a role in both iron storage and immune defense against microbial
      infections.

PMID- 20152907
TI  - Insight into the patterns of cerebrospinal fluid flow in the human ventricular
      system using MR velocity mapping.
AB  - The patterns of cerebrospinal fluid (CSF) flow within the human ventricular
      system are still not fully understood in all their complexity. Knowledge is based
      on either the interpretation of CSF flow curves or computational simulations.
      Both approaches only provide an incomplete insight into the spatial and temporal
      dynamics of CSF flow. Time-resolved three-dimensional magnetic resonance velocity
      mapping has previously been used to investigate normal and pathologic blood flow
      patterns in the human vascular system. Here we used this technique to study the
      spatial and temporal dynamics of CSF flow in the ventricular system of 40 normal
      volunteers. Classification of the patterns of CSF flow based on calculation of
      three-dimensional particle path lines over the cardiac cycle revealed one uniform
      flow pattern for the lateral ventricles, three categories for the third and two
      categories for the fourth ventricle. We found no significant aging effects on
      either the presence of a specific CSF flow pattern or on CSF flow velocities. Our
      results provide the first detailed demonstration of the patterns of CSF flow
      within the human ventricular system.

PMID- 20152906
TI  - Rostral Cingulate Zone and correct response monitoring: ICA and source
      localization evidences for the unicity of correct- and error-negativities.
AB  - Falkenstein et al. (1991) first described a negative wave occurring just after an
      erroneous response in choice Reaction time tasks ("Error Negativity"-Ne or "Error
      Related Negativity"-ERN). Thanks to Laplacian transform of the data, Vidal et al.
      (2000, 2003a) described a wave on correct trials with similar topography and
      latency, although of smaller amplitude compared to the errors. A critical
      question is whether the Ne observed on errors and the negativity reported on
      correct trials reflect the same (modulated) activity, or whether they reflect
      completely different mechanisms. These two alternative possibilities were tested
      thanks to Independent Component Analysis (ICA) and source localization. ICA
      results showed that the waves recorded on errors and correct trials can be
      accounted for by the same independent component, corresponding to a dipolar
      source located within the Rostral Cingulate Zone. Source localization on the raw
      data also confirmed a common generator for correct and error trials. These data
      suggest that the waves on errors and correct trials reflect the same brain
      activity, whose amplitude varies as a function of the correctness of the
      response. The implications of this result for cognitive control are discussed.

PMID- 20152908
TI  - Neural correlates of stimulus-invariant decisions about motion in depth.
AB  - Perceptual decision-making is a complicated, multi-stage process. Recently human
      neuroimaging studies implicated a set of regions, extending from the medial
      frontal cortex to the inferior parietal lobule that are involved in various steps
      of perceptual judgments. However, relatively little is known about the dependence
      of perceptual decisions on the visual stimulus itself. In the current study, we
      used functional magnetic resonance imaging to map neural activations while
      subjects performed a demanding 3D heading estimation task (heading slightly to
      the left or right of fixation). Subjects (n=13) were presented a constantly
      expanding optic-flow stimulus, composed of disparate red-blue spheres, viewed
      stereoscopically through red-blue glasses. We varied task difficulty either by
      adding incoherently moving spheres to the stimuli, hence reducing the strength of
      the motion signal and thereby increasing the amount of noise or by reducing the
      relevant differential information by decreasing the deviation of the average
      trajectory of the spheres from straight ahead. BOLD signals were compared during
      "easy" and "hard" trials in both stimulation conditions to isolate the neural
      mechanisms underlying the decision process. We hypothesized that areas involved
      in perceptual decisions about motion should exhibit significantly different
      activation across both stimulus conditions. Our results indicate that during
      earlier, sensory-stimulation-related phases of decision-making the left
      dorsolateral prefrontal cortex, posterior cingulate and inferior parietal cortex
      showed more activation for the "easy" compared to the "hard" trials, while during
      later, response-related phases the bilateral precuneus and inferior parietal
      cortex, as well as the bilateral superior medial gyrus showed this pattern of
      activation. Our results suggest that a large, non-overlapping network of areas is
      involved in various steps of decisions regarding 3D motion.

PMID- 20152909
TI  - Life-long increase of substantia nigra hyperechogenicity in transcranial
      sonography.
AB  - Transcranial ultrasound of the substantia nigra (SN) shows a distinct
      hyperechogenicity in the majority of patients with Parkinson's disease. Recent
      studies indicate a larger area of hyperechogenicity in elderly healthy adult
      subjects. The present study aimed to determine the size of the SN
      hyperechogenicity and of the mesencephalic brainstem in children and adults
      without evidence of movement disorders. The areas of echogenicity in the
      substantia nigra (aSN) and the area of the ipsilateral midbrain (aMid) were
      assessed in 121 healthy infants and children as well as in 64 healthy adults.
      Furthermore, the ratio of aSN and aMid was calculated (S/M ratio). We found a
      positive correlation between age and aSN and between age and the S/M ratio. The
      values for aSN and S/M ratio were smaller in infants and children compared to
      healthy adults (aSNmax 0.06+/-0.05 cm2 vs. 0.13+/-0.08 cm2). The aSN and S/M
      ratio grew with increasing age in an almost linear progression. The increase of
      SN hyperechogenicity over time suggests that the biological process underlying
      this ultrasound finding may be more dynamic and possibly progressive than
      previously thought.

PMID- 20152911
TI  - Nucleotide substitution rates for the full set of mitochondrial protein-coding
      genes in Coleoptera.
AB  - The ages of cladogenetic events in Coleoptera are frequently estimated with
      mitochondrial protein-coding genes (MPCGs) and the "standard" mitochondrial
      nucleotide substitution rate for arthropods. This rate has been used for
      different mitochondrial gene combinations and time scales despite it was
      estimated on short mitochondrial sequences from few comparisons of close related
      species. These shortcomings may cause greater impact at deep phylogenetic levels
      as errors in rates and ages increase with branch lengths. We use the full set of
      MPCGs of 15 species of beetles (two of them newly sequenced here) to estimate the
      nucleotide evolutionary rates in a reconstructed phylogeny among suborders,
      paying special attention to the effect of data partitioning and model choices on
      these estimations. The optimal strategy for nucleotide data, as measured with
      Bayes factors, was partitioning by codon position. This retrieved Adephaga as a
      sister group to Myxophaga with strong support (expected-likelihood weights test
      0.94-1) and both sisters to Polyphaga, in contradiction with the most currently
      accepted views. The hypothesis of Archostemata being sister to the remaining
      Coleoptera, which is in agreement with morphology, was increasingly supported
      when third codon sites were recoded or completely removed, sequences were
      analyzed as AA, and heterogeneous models were implemented but the support levels
      remained low. Nucleotide substitution rates were strongly affected by the choice
      of data partitioning (codon position versus individual genes), with up to sixfold
      levels of variation, whereas differences in the molecular clock algorithm
      produced changes of only about 20%. The global mitochondrial protein coding rate
      using codon partitioning and an estimated age of 250 million years (MY) for the
      origin of the Coleoptera was 1.34% per branch per MY, which closely matches the
      'standard' clock of 1.15% per MY. The estimation of the rates on alternative
      topologies gave similar results. Using local molecular clocks, the evolutionary
      rate in the Polyphaga and Archostemata was estimated to be nearly twice as fast
      as in the Adephaga and Myxophaga (1.03% versus 0.53% per MY). Rates across
      individual genes varied from 0.55% to 8.61% per MY. Our results suggest that cox1
      might not be an optimal gene for implementing molecular clocks in deep
      phylogenies for beetles because it shows relatively slow rates at first and
      second codon positions but very fast rates at third ones. In contrast, nad5, nad4
      and nad2 perform better, as they exhibit more homogeneous rates among codon
      positions.

PMID- 20152912
TI  - Mitochondrial genome evolution in Ophiuroidea, Echinoidea, and Holothuroidea:
      insights in phylogenetic relationships of Echinodermata.
AB  - The genome architecture and amino acid sequences of six new complete
      mitochondrial genomes were determined from representatives of Hemichordata (1),
      Ophiuroidea (3), Echinoidea (1) and Holothuroidea (1) and were analysed together
      with previously known sequences. Phylogenetic analyses recovered three lineages
      within echinoderms, Crinoidea, Ophiuroidea and a group comprising Holothuroidea,
      Echinoidea, and Asteroidea. In contrast to previous analyses of mitochondrial
      genomes the increased data set recovered the classical echinoderm phylogeny of
      Eleutherozoa and Echinozoa in Maximum Likelihood and Bayesian analyses using
      hemichordate out-group representatives. However, an inconsistent ramification
      appeared with vertebrate out-groups and in Maximum Parsimony and Neighbour
      Joining reconstructions. The basal (consensus) gene orders of all three lineages
      could be derived from a hypothetical ancestral crinoid gene order by one single
      rearrangement in each lineage. The genome architecture was highly conserved in
      Echinoidea, whereas the highest gene order differences and large amounts of
      unassigned sequences (UAS) were detected in Ophiuroidea, supporting a higher
      evolutionary rate than in any other echinoderm lineage. The variability in gene
      order and UAS regions in ophiuroid genomes suggest dominating rearrangement
      mechanisms by duplication events.

PMID- 20152910
TI  - The construction of a Chinese MRI brain atlas: a morphometric comparison study
      between Chinese and Caucasian cohorts.
AB  - We developed a novel brain atlas template to facilitate computational brain
      studies of Chinese subjects and populations using high quality magnetic resonance
      imaging (MRI) and well-validated image analysis techniques. To explore the
      ethnicity-based structural brain differences, we used the MRI scans of 35 Chinese
      male subjects (24.03+/-2.06 years) and compared them to an age-matched cohort of
      35 Caucasian males (24.03+/-2.06 years). Global volumetric measures were used to
      identify significant group differences in the brain length, width, height and AC
      PC line distance. Using the LONI BrainParser, 56 brain structures were
      automatically labeled and analyzed for all subjects. We identified significant
      ethnicity differences in brain structure volumes, suggesting that a population
      specific brain atlas may be more appropriate for studies involving Chinese
      populations. To address this, we constructed a 3D Chinese brain atlas based on
      high resolution 3.0T MRI scans of 56 right-handed male Chinese volunteers
      (24.46+/-1.81 years). All Chinese brains were spatially normalized by using
      linear and nonlinear transformation via the "AIR Make Atlas" pipeline workflow
      within the LONI pipeline environment. This high-resolution Chinese brain atlas
      was compared to the ICBM152 template, which was constructed using Caucasian
      brains.

PMID- 20152913
TI  - Molecular phylogeny of Menthinae (Lamiaceae, Nepetoideae, Mentheae)--Taxonomy,
      biogeography and conflicts.
AB  - Although the subfamily Nepetoideae (Lamiaceae) is considered to be monophyletic,
      relationships between tribes, subtribes and genera within the subfamily are
      poorly understood as complex and possibly homoplasious morphological characters
      make taxa difficult to delimit. DNA sequence data from three regions
      (chloroplast: trnK intron; trnL-F; nuclear: ITS) in total including 278
      accessions, representing 38 out of 40 genera of subtribe Menthinae and 11
      outgroup genera, were used to reconstruct the evolutionary history, test previous
      hypotheses of classification, explain biogeographic patterns and elucidate
      character evolution. Using maximum parsimony (MP) and Bayesian analysis
      phylogenetic reconstructions based on nuclear and chloroplast sequence data were
      incongruent, consequently the data were analyzed separately. Both nuclear and
      chloroplast datasets provide strong support for three major lineages: the
      "Satureja", "Micromeria" and "Clinopodium" group. The first contains members of
      Satureja and Gontscharovia. In the second lineage Micromeria s.str. and Origanum
      were resolved as monophyletic, Pentapleura and Zataria indicated as sister
      groups. Thymbra includes two species of Satureja turning the latter genus
      polyphyletic. Thymus is revealed as paraphyletic with respect to Argantoniella
      and Saccocalyx in both and Origanum in the plastid dataset only. In the third
      lineage, the Clinopodium-group, branching pattern is highly incongruent among
      datasets and possibly influenced by recent and ancient hybridization, chloroplast
      capture and incomplete lineage sorting. However, identical terminal groups are
      inferred in both analyses. A Madagascan lineage of "Micromeria", sister to the
      recently described South African Killickia, is suggested to represent a new
      genus. The Himalayan Clinopodium nepalense group and the tropical African C.
      abyssinicum alliance are monophyletic but indicated in different positions. Both
      groups appear in the ITS phylogeny in a clade with Cyclotrichium and Mentha,
      relationships not suggested previously. The enigmatic Micromeria cymuligera is
      close to Mentha and possibly is a representative of this genus. Species of
      Acinos, now regarded as part of Clinopodium, are mixed up with species of
      Ziziphora, questioning either the inclusion of Acinos in Clinopodium or generic
      distinctness of Ziziphora. All data sets suggest a monophyly of the New World
      taxa and argue for long distance dispersal from the Old World, rather than a
      vicariance explanation. Bystropogon marks the split up between the two lineages.
      Inclusion of 22 genera intermixed with Clinopodium spp. in the New World clade
      provides evidence that the current circumscription of the genus is highly
      unnatural. Low sequence divergence resulting in low phylogenetic resolution
      especially at the base of the clade indicate a rapid radiation accompanied by
      considerable ecological diversification and speciation.

PMID- 20152915
TI  - Phylogeny of the moss class Polytrichopsida (BRYOPHYTA): Generic-level structure
      and incongruent gene trees.
AB  - Analysis of an extensive new molecular dataset for the moss class Polytrichopsida
      provides convincing support for many traditionally recognised genera and
      identifies higher level phylogenetic structure with a strong geographic
      component. A large apical clade that is most diverse in the northern hemisphere
      is subtended by a grade of southern temperate and tropical genera, while the
      earliest diverging lineages have widely separated relictual distributions.
      However, there is strongly supported topological incongruence between the nuclear
      18S rRNA gene tree and the chloroplast and mitochondrial data for the positions
      of some taxa and notably for the status of Pogonatum. While Pogonatum is
      unambiguously paraphyletic in the 18S tree, it is well supported as monophyletic
      by the combined chloroplast and mitochondrial data, this being corroborated by
      several distinctive morphological synapomorphies and a 51-53 bp deletion in the
      rps4-trnS spacer. We explore various reticulate historical processes and
      methodological issues as possible explanations for incongruence, and suggest that
      either (1) the 18S topology is an artefact created by convergence of
      substitutions at specific sites due to functional and/or molecular-structural
      constraints not accounted for by the model, or (2) the incongruence is a product
      of ancient hybridization events. Under the latter scenario, incongruent
      topologies for Pogonatum are parsimoniously explained if Polytrichum (including
      Polytrichastrum sect. Aporotheca) is ultimately descended from a hybridization
      event involving an extinct maternal taxon derived from the branch ancestral to
      the combined Pogonatum/Polytrichum s.l. clade, and a paternal taxon belonging to
      (or ancestral to) the apical Pogonatum group to which the majority of extant
      species belong. Numerous novel relationships of taxonomic and evolutionary
      significance are supported. Notably, both Polytrichastrum and Oligotrichum are
      polyphyletic. While Polytrichastrum sect. Aporotheca is closely related to
      Polytrichum, other species, including the type, are not. The large majority of
      Oligotrichum species sampled occur in one of two distantly related clades with
      predominantly northern and southern hemisphere distributions, respectively,
      implying convergent evolution of this morphology in each of the two temperate
      zones.

PMID- 20152914
TI  - Phylogeny of the genus Hirundo and the Barn Swallow subspecies complex.
AB  - The cosmopolitan Barn Swallow complex (Hirundo rustica and related Hirundo
      species) provides a model system for studies of mate choice, sexual selection,
      and related topics in behavioral ecology, but the phylogenetic and
      phylogeographic relationships within this group are not yet completely resolved.
      We reconstructed the phylogeny of all 14 species of Hirundo as well as all six
      Barn Swallow (H. rustica) subspecies using maximum likelihood and Bayesian
      methods based on sequences of mitochondrial DNA from six protein-coding genes
      (5217 bp) and one nuclear intron (1039 bp) for most taxa. We found four well
      supported clades within the genus, but low support values for one node decreased
      our ability to determine the relationships among them. H. rustica is recently
      derived and has a wide geographic distribution, and its six subspecies form a
      monophyletic group with respect to other Hirundo species. These subspecies divide
      into two well-supported clades, geographically corresponding to Asia-America and
      Europe-Middle East. The former comprises two groups, an East Asian subspecies
      that is sister to Southeast Asian, American, and Northwest Asian subspecies. In
      the other clade, European and East-Mediterranean subspecies are intermixed and
      both show some divergence from the Egyptian subspecies.

PMID- 20152916
TI  - Molecular phylogeny of the subtribe Melinidinae (Poaceae: Panicoideae: Paniceae)
      and evolutionary trends in the homogenization of inflorescences.
AB  - The subtribe Melinidinae (Poaceae: Panicoideae: Paniceae) includes 14 genera that
      present the PCK photosynthetic subtype in addition to several other unique and
      also common characters. The purpose of this research was (1) to test the
      monophyly of the subtribe Melinidinae, including 331 ndhF sequences of Panicoids
      and related genera, (2) to analyze the phylogenetic relationships among genera of
      Melinidinae using four cpDNA regions, and (3) to study evolutionary trends in the
      homogenization of inflorescences. As a result, the monophyly of Melinidinae is
      supported if Urochloa venosa is excluded from the subtribe. Alloteropsis
      semialata subsp. semialata, an unusual PCK species, is here confirmed within the
      Forest shade clade. Within Melinidinae, Urochloa and Eriochloa appeared as
      paraphyletic and polyphyletic genera, respectively. Finally, the general trend in
      the evolution of the inflorescences in Melinidinae seems to be the reduction from
      non-homogenized to complete homogenized inflorescences.

PMID- 20152917
TI  - Phylogeny and evolution of the Meliphagoidea, the largest radiation of
      Australasian songbirds.
AB  - The Meliphagoidea comprises the largest radiation of Australasian passerines.
      Here we present the first detailed molecular phylogenetic analysis of its
      families and genera, particularly the Acanthizidae, using sequences from nine
      gene regions including both mitochondrial and nuclear DNA. Our results support
      some suggested relationships but challenge other groupings, particularly in
      Meliphagidae and Acanthizidae. Maluridae is sister to all other members of the
      superfamily. With appropriate taxon sampling and multilocus data, we provide the
      first strong molecular evidence supporting earlier recognition of bristlebirds,
      Dasyornis, as a separate family, Dasyornithidae. We further clarify its position
      as sister to Acanthizidae+Pardalotidae+Meliphagidae. Pardalotidae is sister to
      Acanthizidae, and thus its retention as a separate family is arbitrary. The
      meliphagid genus Lichenostomus is polyphyletic. We find no support for the
      current subfamily structure within Acanthizidae but recognise a clade that
      includes members of the subfamily Sericornithinae excluding Oreoscopus and
      Acanthornis. Subfamily Acanthizinae is paraphyletic. Surprisingly, the Tasmanian
      island endemic Acanthornis magna of mesic habitats is sister to the Aphelocephala
      whitefaces of mainland Australian xeric zones. This is one of several unexpected
      alignments of taxa as sisters that probably reflects the age of the
      Meliphagoidea. We find no evidence for separate radiations of New Guinean and
      Australian members of the Meliphagoidea.

PMID- 20152918
TI  - Phylogenetic relationships of hexaploid large-sized barbs (genus Labeobarbus,
      Cyprinidae) based on mtDNA data.
AB  - The phylogenetic relationships among species of the Labeobarbus genus (Teleostei,
      Cyprinidae) which comprises large body-sized hexaploid taxa were inferred using
      complete cytochrome b mitochondrial gene sequences. Molecular data suggest two
      main evolutionary groups which roughly correspond to a Northern (Middle East and
      Northwest Africa) and a sub-Saharan lineage. The splitting of the African
      hexaploids from their Asian ancestors and their subsequent diversification on the
      African continent occurred in the Late Miocene, a period in which other cyprinins
      also invaded Africa and radiated in the Mediterranean region. Finally, systematic
      implications of these results to the taxonomic validity of genera or subgenera
      such as Varicorhinus, Kosswigobarbus, Carasobarbus and Capoeta are further
      discussed.

PMID- 20152919
TI  - Heat resistance of Clostridium sordellii spores.
AB  - The thermal destruction kinetics of Clostridium sordellii spores was studied in
      this research. Decimal reduction times (D values) for C. sordellii ATCC 9714
      spores ranged between 175.60 min for D(80) (the D value for spore suspensions
      treated at 80 degrees C) and 11.22 min for D(95). The thermal resistance (Z) and
      temperature coefficient (Q(10)) values of spores were calculated to be as high as
      12.59 degrees C and 6.23, respectively. At 95 degrees C, the relative thermal
      death rate and relative thermal death time of C. sordellii ATCC 9714 spores were
      found to be 0.0085/min and 118 min, respectively, indicating that the death rate
      of spores was 118 times lower at 95 degrees C than at 121.1 degrees C. Heat
      treatments at up to 85 degrees C for 120 min failed to cause a 100-fold
      destruction in spore populations of C. sordellii ATCC 9714. By contrast, spore
      counts were reduced by 2 log(10) cycles within 73 min and 23 min at 90 degrees C
      and 95 degrees C, respectively. This is the first published report of thermal
      inactivation of C. sordellii spores; however, further studies are needed to
      confirm these results in real food samples.

PMID- 20152920
TI  - Characterization of a bacteriocin produced by Lactobacillus sakei R1333 isolated
      from smoked salmon.
AB  - Strain R1333, isolated from commercially available smoked salmon, was identified
      as Lactobacillus sakei based on biochemical tests, sugar fermentation reactions
      (API 50 CHL), PCR with species-specific primers and sequencing of the 16S rRNA
      gene. Strain R1333 produces a 3811 kDa class IIa bacteriocin, active against
      Streptococcus caprinus, Streptococcus macedonicus, Streptococcus spp., L. sakei,
      Lactococcus lactis subsp. lactis, Listeria innocua, Listeria ivanovii subsp.
      ivanovii and Listeria monocytogenes. The mode of activity against L. innocua
      2030C and L. ivanovii subsp. ivanovii ATCC 19119 was bactericidal, resulting in
      cell lysis and enzyme- and DNA-leakage. The highest level of activity (1600
      AU/mL) was recorded when cells were grown at 30 degrees C in MRS broth (initial
      pH 6.5). Only 800 AU/mL was recorded when strain R1333 was grown in MRS without
      Tween 80. Lower levels of bacteriocin production were recorded when strain R1333
      was grown in MRS at 20 degrees C. Peptide R1333 adsorbs at low levels (200 AU/mL)
      to producer cells. Purification of bacteriocin R1333 was performed by 60%
      ammonium sulfate precipitation, followed by separation on a SepPak C(18) column
      and reverse-phase HPLC on a Nucleosil C(18) column with a linear gradient from
      0.1% TFA to 90% acetonitryl. A molecular mass of 3811 kDa was determined by mass
      spectrometry. Based on mass spectrometry and sequencing of the PCR amplified
      fragment targeting the sakG gene, L. sakei R1333 is a potential producer of
      sakacin G. This is the first report of the identification of sakacin G produced
      by L. sakei isolated from smoked salmon.

PMID- 20152922
TI  - MicroRNAs as genetic sculptors: fishing for clues.
AB  - microRNAs (miRNAs) encode small RNA molecules of approximately 22nts in length
      that regulate the deadenylation, translation, and decay of their target mRNAs.
      The identification of miRNAs in plants and animals has uncovered a new layer of
      gene regulation with important implications for development, cellular homeostasis
      and disease. Because each miRNA is predicted to regulate several hundred genes, a
      major challenge in the field remains to elucidate the precise roles for each
      miRNA and to understand the physiological relevance of individual miRNA-target
      interactions in vivo. Despite the wide variety of biological contexts where
      miRNAs function, a common theme emerges, whereby miRNAs shape gene expression
      within both spatial and temporal dimensions by removing messages from previous
      cellular states as well as modulating the levels of actively transcribed genes.
      This review will focus on the role that the teleost Danio rerio (zebrafish) has
      played in shaping our understanding of miRNA function in vertebrates.

PMID- 20152921
TI  - NCI First International Workshop on The Biology, Prevention, and Treatment of
      Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Report from the
      Committee on the Biology Underlying Recurrence of Malignant Disease following
      Allogeneic HSCT: Graft-versus-Tumor/Leukemia Reaction.
AB  - The success of allogeneic hematopoietic stem cell transplantation (HSCT) depends
      on the infusion of benign stem cells as well as lymphocytes capable of
      participating in a graft-versus-tumor/leukemia (GVL) reaction. Clinical proof of
      concept is derived from studies showing increased relapse after the infusion of
      lymphocyte depleted hematopoietic grafts as well as the therapeutic efficacy of
      donor lymphocyte infusions without chemotherapy to treat relapse in some
      diseases. Despite this knowledge, relapse after allogeneic HSCT is common with
      rates approaching 40% in those with high-risk disease. In this review, we cover
      the basic biology and potential application to exploit adaptive T cell responses,
      minor histocompatibility antigens, contraction and suppression mechanisms that
      hinder immune responses, adaptive B cell responses and innate NK cell responses,
      all orchestrated in a GVL reaction. Optimal strategies to precisely balance
      immune responses to favor GVL without harmful graft-versus-host disease (GVHD)
      are needed to protect against relapse, treat persistent disease and improve
      disease-free survival after HSCT.

PMID- 20152924
TI  - Cytosolic carbonic anhydrase in the Gulf toadfish is important for tolerance to
      hypersalinity.
AB  - Carbonic anhydrase (CA) is a ubiquitous enzyme involved in acid-base regulation
      and osmoregulation. Many studies have demonstrated a role for this enzyme in fish
      osmoregulation in seawater as well as freshwater. However, to date CA responses
      of marine fish exposed to salinities exceeding seawater (approximately 35 ppt)
      have not been examined. Consequently, the aim of the present study was to examine
      CA expression and activity in osmoregulatory tissues of the Gulf Toadfish,
      Opsanus beta, following transfer to 60 ppt. A gene coding, for CAc of 1827 bp
      with an open reading frame of 260 amino acids was cloned and showed high
      expression in all intestinal segments and gills. CAc showed higher expression in
      posterior intestine and rectum than in anterior and mid intestine and in gills of
      fish exposed to 60 ppt for up to 4 days. The enzymatic activity, in contrast, was
      higher in all examined tissues two weeks following transfer to 60 ppt. Comparing
      early expression and later activity levels of acclimated fish reveals a very
      different response to hypersalinity among tissues. Results highlight a key role
      of CAc in osmoregulation especially in distal regions of the intestine; moreover,
      CAc play a role in the gill in hypersaline environments possibly supporting
      elevated branchial acid extrusion seen under such conditions.

PMID- 20152923
TI  - MicroRNAs in mouse development and disease.
AB  - MicroRNAs, small non-coding RNAs which act as repressors of target genes, were
      discovered in 1993, and since then have been shown to play important roles in the
      development of numerous systems. Consistent with this role, they are also
      implicated in the pathogenesis of multiple diseases. Here we review the
      involvement of microRNAs in mouse development and disease, with particular
      reference to deafness as an example.

PMID- 20152925
TI  - Structural determinants for calcium mobilization by prostaglandin E2 and
      prostaglandin F2alpha glyceryl esters in RAW 264.7 cells and H1819 cells.
AB  - 2-Arachidonoylglycerol is oxygenated by cyclooxygenase-2 to form prostaglandin
      glyceryl esters. Previous work in this laboratory has suggested that PGE(2)-G
      activates a novel G protein-coupled receptor in a murine macrophage-like cell
      line, RAW 264.7. To probe the structural determinants for the putative receptor
      in RAW 264.7 cells, a panel of 10 analogs was tested for their ability to
      increase intracellular calcium. These analogs included PGE(2)- and PGF(2alpha)
      ethanolamide, 4 PGE(2) glyceryl ester analogs, and 4 PGF(2alpha) glyceryl ester
      analogs. The glyceryl ester analogs differed in the positioning of the hydroxyl
      groups in the glycerol moiety and the type of linker (ester, amide, or thioester)
      of the prostaglandin to the glycerol moiety. Compounds were also evaluated in a
      human non-small cell lung cancer cell line (H1819). The glycerol moiety was
      required for the calcium response. All glyceryl ester analogs but not
      ethanolamides caused a concentration-dependent increase in calcium levels in both
      RAW 264.7 and H1819 cells. An amide or ester linkage was preferable to a
      thioester linkage. The EC(50) values did not significantly change when the
      positioning of the hydroxyls was varied. This calcium response induced by the
      glyceryl ester analogs appears to be independent of the putative hydrolysis
      products, PGE(2) and PGF(2alpha), and appears to represent a novel signaling
      pathway.

PMID- 20152926
TI  - Evaluation of the adjuvant activity of naloxone, an opioid receptor antagonist,
      in combination with heat-killed Listeria monocytogenes vaccine.
AB  - We have previously demonstrated the adjuvant activity of naloxone (NLX), a
      general opioid antagonist, using a DNA vaccine for herpes simplex virus type 1.
      Here, the adjuvant activity of NLX has been evaluated using a heat-killed
      Listeria monocytogenes (HKLM) vaccine as a model for general immunization against
      intracellular bacteria. BALB/c mice were divided into three groups: the Vac group
      received the HKLM vaccine alone; the NLX-Vac group received the HKLM vaccine in
      combination with the adjuvant NLX; and the control group received phosphate
      buffered saline (PBS). Our results indicate that the administration of NLX as an
      adjuvant enhances the ability of the HKLM vaccine to increase lymphocyte
      proliferation, delayed type hypersensitivity, and skewing of the immune response
      toward a T-helper 1 (Th1) pattern. Additionally, combination of NLX with the HKLM
      vaccine improves protective immunity against L. monocytogenes. In conclusion,
      administration of NLX as an adjuvant for the HKLM vaccine can enhance cell
      mediated immunity and shift the immune response to Th1.

PMID- 20152927
TI  - Soil-surface genotoxicity of military and urban territories in Lithuania, as
      revealed by Tradescantia bioassays.
AB  - The soil surface is a major natural system that accumulates pollutants and allows
      researchers to disclose the history and the present state of contamination of an
      area with toxic pollutants. This conclusion is based on the comparison of
      genotoxicity of aqueous extracts and DMSO extracts of topsoil from military
      territories in various locations left behind after the retreat of the Soviet Army
      from Lithuania, and several sites in the city of Vilnius, characterized by
      different history and current traffic intensity. The specific character of the
      soil-surface contamination was shown in a series of Tradescantia micronucleus
      (Trad-MN) and stamen-hair mutation (Trad-SHM) bioassays and tests. The most
      effective ones were the Trad-MN and, unexpectedly, the branched-hair tests. A
      preliminary result of the study is the somaclonal variation of individual
      Tradescantia plants revealed by the RAPD method of DNA analysis. A comparison of
      aqueous extracts and DMSO extracts of the soil showed the permanent character of
      the mobile forms of genotoxic pollutants in the soil surface, despite the fact
      that several military territories were already closed 20 years ago.

PMID- 20152928
TI  - Reactive oxygen species promote localized DNA damage in glaucoma-iris tissues of
      elderly patients vulnerable to diabetic injury.
AB  - Glaucoma is typically an insidious-onset disease with serious visual consequences
      that has been positively linked to diabetes mellitus (DM). Glaucoma is more often
      present in the elderly. Important prognostic factors of glaucoma may be oxidative
      stress resulting from the toxic effects of glucose, and diabetes-associated
      vascular complications. Fifty-five patients and control subjects aged 71.0+/-10.1
      yrs were enrolled in this study. Iris-tissue samples from DM type-2 patients,
      primary open-angle glaucoma-positive and -negative DM patients, and from healthy
      subjects were examined by use of the alkaline comet assay. We measured the DNA
      damage as numbers of strand breaks (SBs), oxidized purines as glycosyl-formamido
      glycosylase (Fpg)-susceptible sites, and oxidized pyrimidines as endonuclease III
      (Nth)-susceptible sites. It was found that the level of oxidative damage in iris
      tissue was statistically higher in DM and glaucoma patients than that in healthy
      controls (oxidized purines: 38.0% and 34.7% vs 15.4%; oxidized pyrimidines: 43.3%
      and 39.0% vs 23.3%; P<0.001). Interestingly, we found strongly elevated levels of
      oxidized purines and pyrimidines in glaucomatous patients who also had DM, in
      comparison with healthy controls (oxidized purines: 55.7% vs 15.4%; oxidized
      pyrimidines: 61.8% vs 23.3%; P<0.001). Our observations suggest that the
      generation of reactive oxygen species may promote localized DNA damage in
      glaucoma-iris tissues of elderly patients vulnerable to diabetic injury.

PMID- 20152929
TI  - Genotoxicity testing of sulfur dioxide (SO2) in a mouse bone marrow micronucleus
      test complemented with hematological endpoints.
AB  - Sulfur dioxide (SO2) is a non-flammable, non-explosive, colorless gas. It is a
      ubiquitous environmental pollutant and an important chemical intermediate in
      several industrial processes. The toxicological properties of SO2, including its
      genotoxic potential, have been studied extensively. The majority of the available
      in vitro data indicate a lack of genotoxicity of SO2, while for sulfite salts
      some positive results have been reported. However, recent in vivo studies, using
      Kunming albino mice, have pointed to in vivo clastogenicity of SO2. To re
      evaluate these positive findings, a bone-marrow micronucleus test according to
      OECD Guideline No. 474 was performed. NMRI mice (m/f) were exposed by inhalation
      via whole-body exposure to 0 (clean air), 2.7, 8, 27, or 80mg/m3 (0, 1, 3, 10, or
      30ppm) SO2 for 4h/day on 7 consecutive days. Animals were sacrificed 24h after
      start of the last exposure, and blood samples (for complementing hematology) and
      bone marrow smears (for analysis of micronuclei) were prepared. Under the
      conditions used, exposure to SO2 caused no acute toxicity, mortality, or
      reduction in body weight. Compared with the clean-air controls, hematological
      parameters such as hematocrit, hemoglobin, erythrocyte/platelet/total leukocyte
      counts, differential white blood cell counts, and indicators of blood formation
      (reticulocyte counts, ratio of polychromatic to normochromatic erythrocytes in
      the bone marrow) remained unchanged by SO2 treatment. Unlike the previously
      reported studies on micronucleus formation, SO2 did not induce micronuclei in
      polychromatic erythrocytes of the bone marrow, whereas the positive control
      cyclophosphamide (60mg/kg body weight) was quite effective in this respect.
      Interestingly, SO2 treatment significantly enhanced malondialdehyde levels in
      erythrocyte lysates (TBARS method), indicating SO2-mediated oxidative stress, but
      also demonstrating systemic availability of the inhaled SO2. In conclusion, the
      present study could not reproduce the genotoxicity findings of the previously
      reported studies. SO2 is thus considered non-genotoxic in polychromatic
      erythrocytes in the bone marrow of NMRI mice under the conditions and in the
      concentrations used.

PMID- 20152930
TI  - Preface. The seventh Special Issue of ASD: "The Fossil Record and Phylogeny of
      the Arthropoda".

PMID- 20152931
TI  - Comparing risks of alternative medical diagnosis using Bayesian arguments.
AB  - This paper explains the role of Bayes Theorem and Bayesian networks arising in a
      medical negligence case brought by a patient who suffered a stroke as a result of
      an invasive diagnostic test. The claim of negligence was based on the premise
      that an alternative (non-invasive) test should have been used because it carried
      a lower risk. The case raises a number of general and widely applicable concerns
      about the decision-making process within the medical profession, including the
      ethics of informed consent, patient care liabilities when errors are made, and
      the research problem of focusing on 'true positives' while ignoring 'false
      positives'. An immediate concern is how best to present Bayesian arguments in
      such a way that they can be understood by people who would normally balk at
      mathematical equations. We feel it is possible to present purely visual
      representations of a non-trivial Bayesian argument in such a way that no
      mathematical knowledge or understanding is needed. The approach supports a wide
      range of alternative scenarios, makes all assumptions easily understandable and
      offers significant potential benefits to many areas of medical decision-making.

PMID- 20152932
TI  - Exploring the ncRNA-ncRNA patterns based on bridging rules.
AB  - ncRNAs play an important role in the regulation of gene expression. However, many
      of their functions have not yet been fully discovered. There are complicated
      relationships between ncRNAs in different categories. Finding these relationships
      can contribute to identify ncRNAs' functions and properties. We extend the
      association rule to represent the relationship between two ncRNAs. Based on this
      rule, we can speculate the ncRNA's function when it interacts with other ncRNAs.
      We propose two measures to explore the relationships between ncRNAs in different
      categories. Entropy theory is to calculate how close two ncRNAs are. Association
      rule is to represent the interactions between ncRNAs. We use three datasets from
      miRBase and RNAdb. Two from miRBase are designed for finding relationships
      between miRNAs; the other from RNAdb is designed for relationships among miRNA,
      snoRNA and piRNA. We evaluate our measures from both biological significance and
      performance perspectives. All the cross-species patterns regarding miRNA that we
      found are proven correct using miRNAMap 2.0. In addition, we find novel cross
      genomes patterns such as (hsa-mir-190b-->hsa-mir-153-2). According to the
      patterns we find, we can (1) explore one ncRNA's function from another with known
      function and (2) speculate the functions of both of them based on the
      relationship even we do no understand either of them. Our methods' merits also
      include: (1) they are suitable for any ncRNA datasets and (2) they are not
      sensitive to the parameters.

PMID- 20152933
TI  - Towards an ontological theory of substance intolerance and hypersensitivity.
AB  - A proper ontological treatment of intolerance--including hypersensitivity--to
      various substances is critical to patient care and research. However, existing
      methods and standards for documenting these conditions have flaws that inhibit
      these goals, especially translational research that bridges the two activities.
      In response, I outline a realist approach to the ontology of substance
      intolerance, including hypersensitivity conditions. I defend a view of these
      conditions as a subtype of disease. Specifically, a substance intolerance is a
      disease whose pathological process(es) are realized upon exposure to a quantity
      of substance of a particular type, and this quantity would normally not cause the
      realization of the pathological process(es). To develop this theory, it was
      necessary to build pieces of a theory of pathological processes. Overall,
      however, the framework of the Ontology for General Medical Science (which uses
      Basic Formal Ontology as its uppermost level) was a more-than-adequate foundation
      on which to build the theory.

PMID- 20152934
TI  - Cross-product extensions of the Gene Ontology.
AB  - The Gene Ontology (GO) consists of nearly 30,000 classes for describing the
      activities and locations of gene products. Manual maintenance of ontology of this
      size is a considerable effort, and errors and inconsistencies inevitably arise.
      Reasoners can be used to assist with ontology development, automatically placing
      classes in a subsumption hierarchy based on their properties. However, the
      historic lack of computable definitions within the GO has prevented the user of
      these tools. In this paper, we present preliminary results of an ongoing effort
      to normalize the GO by explicitly stating the definitions of compositional
      classes in a form that can be used by reasoners. These definitions are
      partitioned into mutually exclusive cross-product sets, many of which reference
      other OBO Foundry candidate ontologies for chemical entities, proteins,
      biological qualities and anatomical entities. Using these logical definitions we
      are gradually beginning to automate many aspects of ontology development,
      detecting errors and filling in missing relationships. These definitions also
      enhance the GO by weaving it into the fabric of a wider collection of
      interoperating ontologies, increasing opportunities for data integration and
      enhancing genomic analyses.

PMID- 20152935
TI  - UMLS content views appropriate for NLP processing of the biomedical literature
      vs. clinical text.
AB  - Identification of medical terms in free text is a first step in such Natural
      Language Processing (NLP) tasks as automatic indexing of biomedical literature
      and extraction of patients' problem lists from the text of clinical notes. Many
      tools developed to perform these tasks use biomedical knowledge encoded in the
      Unified Medical Language System (UMLS) Metathesaurus. We continue our exploration
      of automatic approaches to creation of subsets (UMLS content views) which can
      support NLP processing of either the biomedical literature or clinical text. We
      found that suppression of highly ambiguous terms in the conservative AutoFilter
      content view can partially replace manual filtering for literature applications,
      and suppression of two character mappings in the same content view achieves 89.5%
      precision at 78.6% recall for clinical applications.

PMID- 20152937
TI  - Flourine-18 flourodeoxyglucose positron emission tomography as a non-invasive
      test of disease activity in Takayasu's arteritis--a report of four cases.
AB  - BACKGROUND: Takayasu's arteritis (TA) is a rare disease affecting the large
      arteries, particularly the aorta. Standard test to demonstrate abnormal vascular
      anatomy is angiography. This invasive procedure is limited in differentiating
      inflammatory and fibrotic lesions. Acute phase reactants have shown to have poor
      sensitivity and specificity in confirming disease activity in TA patients.
      Fluorine-18 flourodeoxyglucose Positron Emission Tomography (FDG-PET) scan has
      been utilized to detect areas of active inflammation in neoplastic, infectious
      and recently, vasculitic conditions. OBJECTIVE: To describe the FDG-PET scan
      findings of patients with Takayasu's arteritis. METHODS: This is a case series of
      four patients fulfilling the American College of Rheumatology classification
      criteria for TA. They were evaluated with FDG-PET scan to establish disease
      activity in correlation with other clinical and laboratory features. RESULTS:
      Three out of four patients showed evidence of increased radiotracer uptake in the
      aorta. Of these three patients, one had increased radiotracer uptake in the lungs
      secondary to active pulmonary tuberculosis. CONCLUSION: PET scan is a promising
      but non-specific tool that provides clinicians with a non-invasive measure of
      disease activity in TA patients. Further studies confirming its utility in
      monitoring disease activity and response to treatment is recommended.

PMID- 20152936
TI  - Protein homeostasis and aging: The importance of exquisite quality control.
AB  - All cells count on precise mechanisms that regulate protein homeostasis to
      maintain a stable and functional proteome. A progressive deterioration in the
      ability of cells to preserve the stability of their proteome occurs with age and
      contributes to the functional loss characteristic of old organisms. Molecular
      chaperones and the proteolytic systems are responsible for this cellular quality
      control by assuring continuous renewal of intracellular proteins. When protein
      damage occurs, such as during cellular stress, the coordinated action of these
      cellular surveillance systems allows detection and repair of the damaged
      structures or, in many instances, leads to the complete elimination of the
      altered proteins from inside cells. Dysfunction of the quality control mechanisms
      and intracellular accumulation of abnormal proteins in the form of protein
      inclusions and aggregates occur in almost all tissues of an aged organism.
      Preservation or enhancement of the activity of these surveillance systems until
      late in life improves their resistance to stress and is sufficient to slow down
      aging. In this work, we review recent advances on our understanding of the
      contribution of chaperones and proteolytic systems to the maintenance of cellular
      homeostasis, the cellular response to stress and ultimately to longevity.

PMID- 20152938
TI  - Roles of CC chemokine receptors (CCRs) on lipopolysaccharide-induced acute lung
      injury.
AB  - The aim of the present study was to evaluate the effects of the CC chemokine
      receptor (CCR) 2b and CCR1 antagonist RS504393 as well as the roles of CCRs on
      lipopolysaccharide (LPS)-induced acute lung injury (ALI). In A549 cell line,
      treatment with RS504393 significantly inhibited the expression of CCR1, CCR2 and
      interleukin (IL)-8 after either LPS or tumor necrosis factor-alpha stimulation.
      An ALI model with intranasal LPS administration was used on C57BL/6J, CCR1, CCR2
      and CCR3 knockout mice. Treatment with RS504393 had a noteworthy preventative
      effect on LPS-induced over-expression of IL-1beta, plasminogen activator
      inhibitor and CCR2. In CCR1 and CCR2-deficient animals, LPS-induced less increase
      of lung weight, bronchoalveolar lavage (BAL) leukocytes and IL-6 compared to the
      C57BL/6J and CCR3 knockout mice. This was most prominent in the CCR2 knockout
      mice where no LPS-induced lung edema and no increase of IL-6 in BAL fluid
      occurred. Our results indicate that CCR2, and to some extent CCR1, play pivotal
      roles in the development of ALI.

PMID- 20152939
TI  - Beta sheet 2-alpha helix C loop of cytochrome P450 reductase serves as a docking
      site for redox partners.
AB  - As a promiscuous redox partner, the biological role of cytochrome P450 reductase
      (CPR) depends significantly on protein-protein interactions. We tested a
      hypothesized CPR docking site by mutating D113, E115, and E116 to alanine and
      assaying activity toward various electron acceptors as a function of ionic
      strength. Steady-state cytochrome c studies demonstrated the mutations improved
      catalytic efficiency and decreased the impact of ionic strength on catalytic
      parameters when compared to wild type. Based on activity toward 7-ethoxy-4
      trifluoro-methylcoumarin, CYP2B1 and CPR favored formation of an active
      CYP2B1*CPR complex and inactive (CYP2B1)(2)*CPR complex until higher ionic
      strength whereby only the binary complex was observed. The mutations increased
      dissociation constants only for the binary complex and suppressed the ionic
      strength effect. Studies with a non-binding substrate, 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) suggest changes in activity toward
      cytochrome c and CYP2B1 reflect alterations in the route of electron transfer
      caused by the mutations. Electrostatic modeling of catalytic and binding
      parameters confirmed the importance of D113 and especially the double mutant E115
      and E116 as mediators in forming charge-charge interactions between CPR and
      complex partners.

PMID- 20152940
TI  - Protein disulfide isomerase-P5, down-regulated in the final stage of boar
      epididymal sperm maturation, catalyzes disulfide formation to inhibit protein
      function in oxidative refolding of reduced denatured lysozyme.
AB  - In mammalian spermiogenesis, sperm mature during epididymal transit to get
      fertility. The pig sharing many physiological similarities with humans is
      considered a promising animal model in medicine. We examined the expression
      profiles of proteins from boar epididymal caput, corpus, and cauda sperm by two
      dimensional gel electrophoresis and peptide mass fingerprinting. Our results
      indicated that protein disulfide isomerase-P5 (PDI-P5) human homolog was down
      regulated from the epididymal corpus to cauda sperm, in contrast to the constant
      expression of protein disulfide isomerase A3 (PDIA3) human homolog. To examine
      the functions of PDIA3 and PDI-P5, we cloned and sequenced cDNAs of pig PDIA3 and
      PDI-P5 protein precursors. Each recombinant pig mature PDIA3 and PDI-P5 expressed
      in Escherichia coli showed thiol-dependent disulfide reductase activities in
      insulin turbidity assay. Although PDIA3 showed chaperone activity to promote
      oxidative refolding of reduced denatured lysozyme, PDI-P5 exhibited anti
      chaperone activity to inhibit oxidative refolding of lysozyme at an equimolar
      ratio. SDS-PAGE and Western blotting analysis suggested that disulfide cross
      linked and non-productively folded lysozyme was responsible for the anti
      chaperone activity of PDI-P5. These results provide a molecular basis and
      insights into the physiological roles of PDIA3 and PDI-P5 in sperm maturation and
      fertilization.

PMID- 20152942
TI  - Alkaline pH-dependent differential unfolding characteristics of mesophilic and
      thermophilic homologs of dimeric serine hydroxymethyltransferase.
AB  - Environmental variables such as pH can significantly influence the folding and
      stability of a protein molecule. In the present investigation, we compared the
      alkaline pH-induced unfolding of two homologous serine hydroxymethyltransferase
      from mesophilic Bacillus subtilis (bsSHMT) and thermophilic Bacillus
      stearothermophilus (bstSHMT) using various biophysical techniques. The
      thermophilic enzyme bstSHMT was found to be more resistant to alkaline
      denaturation compared to its mesophilic counterpart, bsSHMT. Unfolding studies
      using domain-swapped chimera, constructed by swapping the C-terminal domain of
      these two wild-type proteins, revealed that C-terminal domain plays a pivotal
      role in the folding, stability and subunit interaction of these proteins. Primary
      amino acid sequence analysis of the proteins showed that bsSHMT has six
      unconserved lysine residues in C-terminal domain, which are absent in bstSHMT.
      Chemical modification of lysine side chains resulted in stabilization of
      monomers, only in case of bsSHMT. Moreover, comparison between homology model of
      bsSHMT with the crystal structure of bstSHMT revealed that a small stretch of 11
      amino acids at the end of C-terminal domain was found protruding outside the
      molecule as a flexible coiled structure in bsSHMT. Taken together these findings
      suggest that possibly the presence of these non-identical lysine moieties and a
      small extension of C-terminal domain may be responsible for low stability of
      bsSHMT under alkaline pH condition.

PMID- 20152941
TI  - Effects on human plasminogen conformation and activation rate caused by
      interaction with VEK-30, a peptide derived from the group A streptococcal M-like
      protein (PAM).
AB  - In vertebrates, fibrinolysis is primarily carried out by the serine protease
      plasmin (Pm), which is derived from activation of the zymogen precursor,
      plasminogen (Pg). One of the most distinctive features of Pg/Pm is the presence
      of five homologous kringle (K) domains. These structural elements possess
      conserved Lys-binding sites (LBS) that facilitate interactions with substrates,
      activators, inhibitors and receptors. In human Pg (hPg), K2 displays weak Lys
      affinity, however the LBS of this domain has been implicated in an atypical
      interaction with the N-terminal region of a bacterial surface protein known as
      PAM (Pg-binding group A streptococcal M-like protein). A direct correlation has
      been established between invasiveness of group A streptococci and their ability
      to bind Pg. It has been previously demonstrated that a 30-residue internal
      peptide (VEK-30) from the N-terminal region of PAM competitively inhibits binding
      of the full-length parent protein to Pg. We have attempted to determine the
      effects of this ligand-protein interaction on the regulation of Pg zymogen
      activation and conformation. Our results show minimal effects on the
      sedimentation velocity coefficients (S degrees (20,w)) of Pg when associated to
      VEK-30 and a direct relationship between the concentration of VEK-30 or PAM and
      the activation rate of Pg. These results are in contrast with the major
      conformational changes elicited by small-molecule activators of Pg, and point
      towards a novel mechanism of Pg activation that may underlie group A
      streptococcal (GAS) virulence.

PMID- 20152943
TI  - Site-directed chemical modification of archaeal Thermococcus litoralis Sh1B DNA
      polymerase: Acquired ability to read through template-strand uracils.
AB  - We present site-directed chemical modification (SDCM), a tool for engineering U
      resistant archaeal DNA polymerases of family B. The Thermococcus litoralis Sh1B
      DNA polymerase (GenBank: GQ891548) was chosen as the object of the study. Similar
      to D.Tok, Kod1, Pfu, Tgo and other archaeal members of this family, the T.
      litoralis Sh1B DNA polymerase is a domain structured, proofreading-proficient
      enzyme that has the polymerization and 3'-->5' DNA exonucleolytic activities and
      contains N-terminally located highly conserved template-strand U-binding pocket.
      The tight binding of template uracil in the enzyme pocket during polymerization
      blocks the replication of DNA containing uracils. This effect can be alleviated
      by mutations in key amino acids of the U-binding pocket. We altered T. litoralis
      Sh1B DNA polymerase's ability to read through the template-strand uracils by
      applying SDCM. Specific modification of individual cysteine residues in U-binding
      pocket - targets introduced into certain positions by site-directed mutagenesis -
      enables the enzyme to effectively replicate DNA containing uracils. We
      demonstrate that the acquired resistance of chemically modified T. litoralis Sh1B
      DNA polymerase to DNA uracil correlates with its decreased affinity for template
      strand uracil.

PMID- 20152944
TI  - Hardness in arthropod exoskeletons in the absence of transition metals.
AB  - The arthropod cuticle is a remarkable and versatile biological material commonly
      composed of chitin and proteins. Lessons can be learned from the way it is
      adapted to fit its functions. The larval jewel beetle, Pseudotaenia frenchi,
      demonstrates hardness in the cutting edge of the mandibles in excess of the
      mineralized carapace of stone crabs and compares favourably with some stainless
      steels. Yet this is a form of cuticle which is devoid of transition metals or
      mineralization. In seeming contradiction, the similarly dark coloured adult
      beetle mandibles contain the transition metal manganese, but are significantly
      softer. Energy dispersive X-ray analysis and infrared spectroscopy have been used
      to investigate the differences in composition of mandible cuticle of the adult
      and larval beetles.

PMID- 20152945
TI  - Light-sensitive intelligent drug delivery systems of coumarin-modified mesoporous
      bioactive glass.
AB  - Functionalized mesoporous bioactive glasses (MBG) with photoactive coumarin
      demonstrates photo-responsive dimerization resulting in reversible gate
      operation. Coumarin-modified MBG was used as a drug delivery carrier to
      investigate drug storage/release characteristics using phenanthrene as a model
      drug. Irradiation with UV light (>310 nm) induced photo-dimerization of the
      coumarin-modified MBG, which led to the pores' closing with cyclobutane dimers
      and trapping of the guest phenanthrene in the mesopores. However, irradiating the
      dimerized-coumarin-modified MBG with shorter wavelength UV light (approximately
      250 nm) regenerates the coumarin monomer derivative by the photo-cleavage of
      cyclobutane dimers, such that trapped guest molecules are released from the
      mesopores. The structural, morphological, textural and optical properties are
      well characterized by X-ray diffraction, transmission electron microscopy, N(2)
      adsorption/desorption, and UV-visible spectroscopy. The results reveal that the
      MBG exhibits the typical ordered characteristics of the hexagonal mesostructure.
      The system demonstrates great potential in light-sensitive intelligent drug
      delivery systems and disease therapy fields.

PMID- 20152946
TI  - Sol-gel silica-based biomaterials and bone tissue regeneration.
AB  - The impact of bone diseases and trauma in developed and developing countries has
      increased significantly in the last decades. Bioactive glasses, especially silica
      based materials, are called to play a fundamental role in this field due to their
      osteoconductive, osteoproductive and osteoinductive properties. In the last
      years, sol-gel processes and supramolecular chemistry of surfactants have been
      incorporated to the bioceramics field, allowing the porosity of bioglasses to be
      controlled at the nanometric scale. This advance has promoted a new generation of
      sol-gel bioactive glasses with applications such as drug delivery systems, as
      well as regenerative grafts with improved bioactive behaviour. Besides, the
      combination of silica-based glasses with organic components led to new organic
      inorganic hybrid materials with improved mechanical properties. Finally, an
      effort has been made to organize at the macroscopic level the sol-gel glass
      preparation. This effort has resulted in new three-dimensional macroporous
      scaffolds, suitable to be used in tissue engineering techniques or as porous
      pieces to be implanted in situ. This review collects the most important advances
      in the field of silica glasses occurring in the last decade, which are called to
      play a lead role in the future of bone regenerative therapies.

PMID- 20152947
TI  - Hydrogel/calcium phosphate composites require specific properties for three
      dimensional culture of human bone mesenchymal cells.
AB  - To provide multipotent cells with a three-dimensional environment closer to bone
      matrix, an engineered construct mimicking bone components has been designed and
      evaluated. A biocompatible hydrogel (silated hydroxypropylmethyl cellulose) was
      used as an extra-cellular matrix while biphasic calcium phosphate ceramic
      particles were used to replace mineralized matrix. Finally, human bone
      mesenchymal cells were cultured in three dimensions in the resulting constructs
      to study their cell viability, proliferation, interactions within the composites,
      and maintenance of their osteogenic potential. This approach resulted in
      homogeneous structures in which cells were viable and retained their osteoblastic
      differentiation potential. However, the cells did not proliferate nor colonize
      the constructs, possibly because of a lack of suitable interactions with their
      micro-environment.

PMID- 20152948
TI  - Perspectives for IJS February, 2010.

PMID- 20152949
TI  - Autosomal dominant microtia.
AB  - Microtia (MIM600674) is a congenital malformation which occurs in 1/8000-10000
      births. It is characterized by a small, and abnormally shaped pinna. It ranges in
      severity from a bump of tissue to a partially formed ear cup. Microtia is often
      associated with atresia of the external auditory canal. Familial microtia with
      meatal atresia has been reported, either with dominant or recessive inheritance,
      which makes genetic counselling difficult in sporadic cases. In the present
      paper, we report the case of a family with congenital microtia and conductive
      deafness in two generations, suggesting autosomal dominant inheritance with
      variable expression and incomplete penetrance.

PMID- 20152950
TI  - Synophrys.
AB  - INTRODUCTION: Meeting of the medial eyebrows in the midline (synophrys) may serve
      as a cutaneous marker lesion for syndromal disorders (e.g. Cornelia de Lange
      syndrome). CASE PRESENTATION: A 31-year-old man showed supercilia forming a
      single band of terminal hairs between left and right lateral orbital rim. Medical
      examination of the patient revealed coldness-inducable urticaria, xanthelasma
      formation and long eyelashes without any signs of a syndromal disorder.
      CONCLUSION: Synophrys can be found in some syndromal disorders, but are not
      pathognomonic for any illness per se.

PMID- 20152951
TI  - Mechanical vibration preserves bone structure in rats treated with
      glucocorticoids.
AB  - Glucocorticoids are an important cause of secondary osteoporosis in humans, which
      decreases bone quality and leads to fractures. Mechanical stimulation in the form
      of low-intensity and high-frequency vibration seems to be able to prevent bone
      loss and to stimulate bone formation. The objective of this study was to evaluate
      the effects of mechanical vibration on bone structure in rats treated with
      glucocorticoids. Thirty 3-month-old adult male Wistar rats were randomized to
      three groups: control (C), glucocorticoid (G), and glucocorticoid with vibration
      (GV). The G and GV groups received 3.5mg/kg/day of methylprednisolone 5 days/week
      for a duration of 9 weeks, and the C group received vehicle (saline solution)
      during the same period. The GV group was vibrated on a special platform for 30
      min per day, 5 days per week during the experiment. The platform was set to
      provide a vertical acceleration of 1 G and a frequency of 60 Hz. Skeletal bone
      mass was evaluated by total body densitometry (DXA). Fracture load threshold,
      undecalcified bone histomorphometry, and bone volume were measured in tibias.
      Glucocorticoids induced a significantly lower weight gain (-9.7%) and reduced the
      bone mineral content (-9.2%) and trabecular number (-41.8%) and increased the
      trabecular spacing (+98.0%) in the G group, when compared to the control (C).
      Vibration (GV) was able to significantly preserve (29.2%) of the trabecular
      number and decrease the trabecular spacing (+26.6%) compared to the G group,
      although these parameters did not reach C group values. The fracture load
      threshold was not different between groups, but vibration significantly augmented
      the bone volume of the tibia by 21.4% in the GV group compared to the C group.
      Our study demonstrated that low-intensity and high-frequency mechanical vibration
      was able to partially inhibit the deleterious consequences of glucocorticoids on
      bone structure in rats.

PMID- 20152952
TI  - Ex vivo culturing of stromal cells with dexamethasone-loaded
      carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles promotes ectopic
      bone formation.
AB  - Recently, our group has proposed a combinatorial strategy in tissue engineering
      principles employing carboxymethylchitosan/poly(amidoamine) dendrimer
      nanoparticles (CMCht/PAMAM) towards the intracellular release and regimented
      supply of dexamethasone (Dex) aimed at controlling stem cell osteogenic
      differentiation in the absence of typical osteogenic inducers, in vivo. In this
      work, we have investigated if the Dex-loaded CMCht/PAMAM dendrimer nanoparticles
      could play a crucial role in the regulation of osteogenesis, in vivo. Macroporous
      hydroxyapatite (HA) scaffolds were seeded with rat bone marrow stromal cells
      (RBMSCs), whose cells were expanded in MEM medium supplemented with 0.01 mg ml(
      1) Dex-loaded CMCht/PAMAM dendrimer nanoparticles and implanted subcutaneously on
      the back of rats for 2 and 4 weeks. HA porous ceramics without RBMSCs and
      RBMSCs/HA scaffold constructs seeded with cells expanded in the presence and
      absence of 10(-8) M Dex were used as controls. The effect of initial cell number
      seeded in the HA scaffolds on the bone-forming ability of the constructs was also
      investigated. Qualitative and quantitative new bone formation was evaluated in a
      non-destructive manner using micro-computed tomography analyses of the explants.
      Haematoxylin and Eosin stained implant sections were also used for the
      histomorphometrical analysis. Toluidine blue staining was carried out to
      investigate the synthesis of proteoglycan extracellular matrix. In addition,
      alkaline phosphatase and osteocalcin levels in the explants were also quantified,
      since these markers denote osteogenic differentiation. At 4 weeks post
      implantation results have shown that the novel Dex-loaded
      carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles may be beneficial
      as an intracellular nanocarrier, supplying Dex in a regimented manner and
      promoting superior ectopic de novo bone formation.

PMID- 20152953
TI  - [Synovial sarcoma of the infratemporal fossa].
AB  - Synovial sarcoma is the fourth most common type of sarcoma. It is usually found
      in the knee or ankle joints, and is exceptional in the head and neck. Most cases
      are diagnosed in men between 20 and 40 years of age. Diagnosis is often casual
      due to the infrequent nature of this tumour and its non-specific clinical and
      radiological characteristics. Confirmation is therefore based on
      immunohistochemistry and electron microscopy techniques. We report a case of
      biphasic sinovial sarcoma located in the infratemporal fossa treated at our
      hospital and we make a review of the literature.

PMID- 20152954
TI  - [Cervical and mediastinum haematoma secondary to spontaneous thyroid rupture].
AB  - We present a case of spontaneous haemorrhage of a thyroid nodule with diffusion
      of the haematoma to cervical spaces and mediastinum, which began as a progressive
      cervical mass affecting the airway and which required surgical treatment for
      control. The diagnosis was made using ultrasonography and cervicothoracic CT
      scan, giving high quality images to determine the site of bleeding as well as the
      extent of the process.

PMID- 20152955
TI  - [Response to metronomic chemotherapy in a metastatic adenoid cystic carcinoma of
      the parotid gland].
AB  - Formerly, salivary gland cancer was considered to be chemoresistant. Chemotherapy
      is indicated when distant metastases or inoperable locorregional disease are
      observed, although the chemotherapy schedule is not well defined. Data on
      chemotherapy treatment for adenoid cystic carcinoma consist of phase II trials.
      Most of these studies analyze therapies with a combination of agents at full
      dose, although there is no clear evidence that such treatment improves survival.
      The administration of cytotoxic agents with low doses at frequent, regular
      intervals with no drug-free interruptions is known as metronomic chemotherapy.
      Most head-to-head studies show similar or even superior therapeutic results with
      metronomic scheduling than with a maximum tolerated dose regime. Our case report
      shows for first time the clinical activity of low-dose paclitaxel and cisplatin
      chemotherapy given separately as a single agent in metastatic adenoid cystic
      carcinoma of the parotid.

PMID- 20152956
TI  - Nanobubbles and the nanobubble bridging capillary force.
AB  - Interactions between hydrophobic surfaces at nanometer separation distances in
      aqueous solutions are important in a number of biological and industrial
      processes. Force spectroscopy studies, most notably with the atomic force
      microscope and surface-force apparatus, have found the existence of a long range
      hydrophobic attractive force between hydrophobic surfaces in aqueous conditions
      that cannot be explained by classical colloidal science theories. Numerous
      mechanisms have been proposed for the hydrophobic force, but in many cases the
      force is an artifact due to the accumulation of submicroscopic bubbles at the
      liquid-hydrophobic solid interface, the so called nanobubbles. The coalescence of
      nanobubbles as hydrophobic surfaces approach forms a gaseous capillary bridge,
      and thus a capillary force. The existence of nanobubbles has been highly debated
      over the last 15 years. To date, experimental evidence is sound but a theoretical
      understanding is still lacking. It is the purpose of this review to bring
      together the many experimental results on nanobubbles and the resulting capillary
      force in order to clarify these phenomena. A review of pertinent nanobubble
      stability and formation theories is also presented.

PMID- 20152957
TI  - Bottle-brush polymers: adsorption at surfaces and interactions with surfactants.
AB  - Solution and adsorption properties of both charged and uncharged bottle-brush
      polymers have been investigated. The solution conformation and interactions in
      solution have been investigated by small-angle scattering techniques. The
      association of the bottle-brush polymers with anionic surfactants has also been
      studied. Surfactant binding isotherm measurements, NMR, surface tension
      measurements, as well as SAXS, SANS and light scattering techniques were utilized
      for understanding the association behaviour in bulk solutions. The adsorption of
      the bottle-brush polymers onto oppositely charged surfaces has been explored
      using a battery of techniques, including reflectometry, ellipsometry, quartz
      crystal microbalance, and neutron reflectivity. The combination of these
      techniques allowed determination of adsorbed mass, layer thickness, water
      content, and structural changes occurring during layer formation. The adsorption
      onto mica was found to be very different to that on silica, and an explanation
      for this was sought by employing a lattice mean-field theory. The model was able
      to reproduce a number of salient experimental features characterizing the
      adsorption of the bottle-brush polymers over a wide range of compositions,
      spanning from uncharged bottle-brushes to linear polyelectrolytes. This allowed
      us to shed light on the importance of electrostatic surface properties and non
      electrostatic surface-polymer affinity for the adsorption. The interactions
      between bottle-brush polymers and anionic surfactants in adsorbed layers have
      also been elucidated using ellipsometry, neutron reflectivity and surface force
      measurements.

PMID- 20152958
TI  - A weighted false discovery rate control procedure reveals alleles at FOXA2 that
      influence fasting glucose levels.
AB  - Association signals in GWAS are usually prioritized solely by p values. Here, we
      attempt to improve the power of GWAS by using a weighted false discovery rate
      control procedure to detect associations of low-frequency variants with effect
      sizes similar to or even larger than those of common variants. We used the
      Affymetrix Genome-Wide Human SNP Array 6.0 to test for association with fasting
      glucose levels in the Atherosclerosis Risk in Communities Study (ARIC)
      population. In addition to finding several previously identified sequence
      variations, we identified a low-frequency variant (rs1209523; minor allele
      frequency = 0.043) near FOXA2 that was associated with fasting glucose levels in
      European Americans (EAs) (n = 7428, p value = 1.3 x 10(-5)). The association
      between rs1209523 and glucose levels was also significant in African Americans
      (AAs) (n = 2029, p value = 6.7 x 10(-3)) of the ARIC and was confirmed by
      replication in both EAs and AAs of the Dallas Heart Study (n = 963 and 1571,
      respectively; p values = 5.3 x 10(-3) and 5.8 x 10(-4), respectively) and in EAs
      of the Cooper Center Longitudinal Study (n = 2862; p value = 1.6 x 10(-2)). A
      meta-analysis of these five populations yielded an estimated effect size of -1.31
      mg/dl per minor allele (p value = 2.2 x 10(-11)). This study reveals that there
      is a cache of less-frequent variants in GWAS arrays that can be identified via
      analytical approaches accounting for allele frequencies.

PMID- 20152959
TI  - Efficacy and tolerability of preservative-free and preserved diclofenac and
      preserved ketorolac eyedrops after cataract surgery.
AB  - PURPOSE: To compare the anti-inflammatory efficacy and subjective tolerability of
      preservative-free and preserved diclofenac 0.1% and preserved ketorolac 0.5% eye
      drops for prophylaxis and management of inflammation after cataract surgery.
      DESIGN: Prospective, randomized, investigator-masked, parallel-group, comparative
      clinical trial. METHODS: One hundred two patients who underwent small-incision
      phacoemulsification cataract surgery in an institutional setting were assigned
      randomly to receive preservative-free diclofenac sodium 0.1% (Voltaren ophtha
      SDU; Novartis Pharma), preserved diclofenac sodium 0.1% (Voltaren ophtha;
      Novartis Pharma), or preserved ketorolac tromethamine 0.5% (Acular; Pharm
      Allergan) eyedrops 4 times daily for 4 weeks after surgery. During the 1-month
      follow-up, anterior chamber flare and mean foveal thickness were evaluated for
      objective comparison of the anti-inflammatory effect. Ocular tolerability was
      assessed by observer-based grading of conjunctival hyperemia and ocular
      discomfort, as well as obtaining subjective ratings of ocular tolerability on a
      visual analog scale. Distance and near visual acuity and intraocular pressure
      served as safety measures. RESULTS: All 3 formulations demonstrated equal anti
      inflammatory efficacy as measured by reduction of anterior chamber flare after
      surgery and prevention of postoperative macular edema. Patients treated with
      preservative-free diclofenac eyedrops reported significantly better subjective
      tolerability values (P = .001), were classified as having less ocular discomfort
      (P < .001), and experienced earlier reduction of postoperative conjunctival
      hyperemia (P = .029). CONCLUSIONS: Anti-inflammatory efficacy was comparable for
      all 3 agents. However, preservative-free diclofenac 0.1% eyedrops exhibited a
      significantly better postoperative subjective and objective tolerability when
      compared with preserved eyedrops containing ketorolac or diclofenac.

PMID- 20152960
TI  - Internet administered guided self-help versus individualized e-mail therapy: A
      randomized trial of two versions of CBT for major depression.
AB  - Internet-delivered psychological treatment of major depression has been
      investigated in several trials, but the role of personalized treatment is less
      investigated. Studies suggest that guidance is important and that automated
      computerized programmes without therapist support are less effective.
      Individualized e-mail therapy for depression has not been studied in a controlled
      trial. Eighty-eight individuals with major depression were randomized to two
      different forms of Internet-delivered cognitive behaviour therapy (CBT), or to a
      waiting-list control group. One form of Internet treatment consisted of guided
      self-help, with weekly modules and homework assignments. Standard CBT components
      were presented and brief support was provided during the treatment. The other
      group received e-mail therapy, which was tailored and did not use the self-help
      texts i.e., all e-mails were written for the unique patient. Both treatments
      lasted for 8 weeks. In the guided self-help 93% completed (27/29) and in the e
      mail therapy 96% (29/30) completed the posttreatment assessment. Results showed
      significant symptom reductions in both treatment groups with moderate to large
      effect sizes. At posttreatment 34.5% of the guided self-help group and 30% of the
      e-mail therapy group reached the criteria of high-end-state functioning (Beck
      Depression Inventory score below 9). At six-month follow-up the corresponding
      figures were 47.4% and 43.3%. Overall, the difference between guided self-help
      and e-mail therapy was small, but in favour of the latter. These findings
      indicate that both guided self-help and individualized e-mail therapy can be
      effective.

PMID- 20152961
TI  - [Fournier gangrene. A retrospective study of 41 cases].
AB  - INTRODUCTION: Fournier's gangrene is a rapidly progressing necrotizing fascitis
      that affects the perineal and genital area. Mortality still remains high. The aim
      of this study was to evaluate the epidemiological progression and morbidity
      mortality of Fournier's gangrene at our centre over the past 10 years. METHODS:
      Retrospective study of 41 patients treated for Fournier's gangrene between 1998
      and 2007. Variables studied included, demographic variables, aetiology,
      microbiology, surgical and antibiotic treatment, morbidity, and mortality.
      RESULTS: The mean age of the patients was 60, and 93% were male. The most common
      co-morbidity was diabetes (49%), followed by alcoholism (46%) and
      immunosuppression or neoplasia (34%). The origin was perianal in 66% of cases,
      followed by a urological origin (32%). The median time from the onset of symptoms
      to diagnosis was 3 days. Several surgical debridements were required in 49% of
      the patients, and the mortality rate was 29%. Most cases had positive cultures
      (93%), and in 76% more than one microorganism was isolated (enterobacteriaceae
      and anaerobic flora). In the bivariate analysis, antimicrobial treatment with
      carbapenems and the absence of systemic complications were associated with lower
      mortality. CONCLUSIONS: Fournier's gangrene continues to be a severe surgical
      emergency, with a high mortality rate. Early diagnosis and aggressive surgical
      and antibiotic therapy are necessary for adequate management.

PMID- 20152962
TI  - Breast-cancer identification using HMM-fuzzy approach.
AB  - This paper presents an ensemble of feature selection and classification technique
      for classifying two types of breast lesion, benign and malignant. Features are
      selected based on their area under the ROC curves (AUC) which are then classified
      using a hybrid hidden Markov model (HMM)-fuzzy approach. HMM generated log
      likelihood values are used to generate minimized fuzzy rules which are further
      optimized using gradient descent algorithms in order to enhance classification
      performance. The developed model is applied to Wisconsin breast cancer dataset to
      test its performance. The results indicate that a combination of selected
      features and the HMM-fuzzy approach can classify effectively the lesion types
      using only two fuzzy rules. Our experimental results also indicate that the
      proposed model can produce better classification accuracy when compared to most
      other computational tools.

PMID- 20152964
TI  - Redox and electrophilic properties of vapor- and particle-phase components of
      ambient aerosols.
AB  - Particulate matter (PM) has been the primary focus of studies aiming to
      understand the relationship between the chemical properties of ambient aerosols
      and adverse health effects. Size and chemical composition of PM have been linked
      to their oxidative capacity which has been postulated to promote or exacerbate
      pulmonary and cardiovascular diseases. But in the last few years, new studies
      have suggested that volatile and semi-volatile components may also contribute to
      many adverse health effects. The objectives of this study were: (i) assess for
      the first time the redox and electrophilic potential of vapor-phase components of
      ambient aerosols and (ii) evaluate the relative contributions of particle- and
      vapor-fractions to the hazard of a given aerosol. To achieve these objectives
      vapor- and particle-phase samples collected in Riverside (CA) were subjected to
      three chemical assays to determine their redox and electrophilic capacities. The
      results indicate that redox active components are mainly associated with the
      particle-phase, while electrophilic compounds are found primarily in the vapor
      phase. Vapor-phase organic extracts were also capable of inducing the stress
      responding protein, heme-oxygenase-1 (HO-1), in RAW264.7 murine macrophages.
      These results demonstrate the importance of volatile components in the overall
      oxidative and electrophilic capacity of aerosols, and point out the need for
      inclusion of vapors in future health and risk assessment studies.

PMID- 20152965
TI  - [Comorbidity and health resources use in smokers. An analysis from a primary care
      setting].
AB  - BACKGROUND: To ascertain the morbidity profile, achievement of the clinical
      control objectives, resources use and the incidence of cardiovascular events
      (CVE) in smoking subjects in Primary Care settings (PC). METHODS: Retrospective
      multicentric study. All smoker subjects older than thirty years attended in any
      of five PC settings were included. A comparative cohort was established with non
      smokers. Primary measures were: presence of CVE, age, gender, Charlson index,
      history/co-morbidity and clinics parameters and direct costs (fixed and variable;
      visits, drugs, diagnostic test and referrals). Multiple logistic regression
      analysis and ANCOVA models were applied for models correction, P<0.05. RESULTS:
      55,653 patients were included. 20.8% (95% confidence intervals [CI]:20.5-21.1%)
      were smokers. Non-smokers were younger (48.2 versus 55.9 years), with more men
      (60.8%), P<0.01; and a similar Charlson index (0.3 versus 0.3; P=NS). The
      proportion of smokers in hypertensive population was 18.8% and in diabetics 9.6%.
      CVE presence in smokers were 4.9% versus 4.2% and the accumulated
      incidence/annual of 14.2 per thousand versus 12.5 per thousand, P<0.028. Smokers
      showed higher levels of serum triglycerides (136.3 mg/dl) and LDL-cholesterol
      (128.0 mg/dl, P<0.001). Smoking habit was independent related to the alcoholism
      (Odds ratio, OR=5.3) and the EPOC (OR=2.5), in presence of CVE (OR=1.2, P<0.001).
      Adjusted direct costs non differences showed: euro660.10 versus euro654.11, P=NS
      (in all components). CONCLUSIONS: CVE annual incidence in smoking subjects was
      greater, with a minor average of age. Smokers presented a similar number of co
      morbidities and total/patient costs. Clinical control objectives should be better
      in Primary prevention of the cardiovascular risk factors. To give up smoking
      should be the best strategy to diminish CVE incidence.

PMID- 20152966
TI  - Sex chromosome micromosaicism in infertile men with normal karyotypes.
AB  - OBJECTIVE: To define the prevalence of low-level sex chromosome mosaicism in a
      cohort of infertile men. DESIGN: Prospective cohort study of infertile men.
      SETTING: Tertiary university infertility center. PATIENT(S): One hundred one
      consecutive men who presented with primary infertility for evaluation.
      INTERVENTION(S): Fluorescent in situ hybridization for X and Y was performed on
      200 cells, and if an aberrant sex chromosome complement was noted, 400 cells were
      counted. For this study, any abnormality in sex chromosome complement was defined
      as micromosaicism. MAIN OUTCOME MEASURE(S): Low-level sex chromosome mosaicism.
      RESULT(S): Sixty-seven of these men (67%) had no mosaicism, and 34 men (34%) had
      micromosaicism. The median percentage of abnormal chromosomes in these men was
      2%. The mean age of the men without micromosaicism was lower than for men with
      micromosaicism (31.1 years vs. 35.2 years). A trend toward higher FSH levels in
      men with low-level mosaicism was seen. Median sperm density and percent motility
      were higher in normal men. Percent normal morphology was identical between
      groups. CONCLUSION(S): We found low-level sex chromosome mosaicism in 34% of
      infertile men who presented for evaluation. Men with low-level mosaicism were
      significantly older. Low-level mosaicism may emerge with advancing age and may
      therefore help to explain the decline in fertility potential seen in older men.

PMID- 20152963
TI  - Evidence for topographic organization in the cerebellum of motor control versus
      cognitive and affective processing.
AB  - Patients with cerebellar damage often present with the cerebellar motor syndrome
      of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in
      the cerebellar cognitive affective syndrome (CCAS), including executive, visual
      spatial, and linguistic impairments, and affective dysregulation. We have
      hypothesized that there is topographic organization in the human cerebellum such
      that the anterior lobe and lobule VIII contain the representation of the
      sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the
      cognitive cerebellum; and the posterior vermis is the anatomical substrate of the
      limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and
      clinical data to test this hypothesis. We find converging lines of evidence
      supporting regional organization of motor, cognitive, and limbic behaviors in the
      cerebellum. The cerebellar motor syndrome results when lesions involve the
      anterior lobe and parts of lobule VI, interrupting cerebellar communication with
      cerebral and spinal motor systems. Cognitive impairments occur when posterior
      lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule
      VIIB), disrupting cerebellar modulation of cognitive loops with cerebral
      association cortices. Neuropsychiatric disorders manifest when vermis lesions
      deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this
      functional topography to be a consequence of the differential arrangement of
      connections of the cerebellum with the spinal cord, brainstem, and cerebral
      hemispheres, reflecting cerebellar incorporation into the distributed neural
      circuits subserving movement, cognition, and emotion. These observations provide
      testable hypotheses for future investigations.

PMID- 20152967
TI  - Melatonin as a potential tool against oxidative damage and apoptosis in
      ejaculated human spermatozoa.
AB  - It is assumed somatic cells can die in the apoptotic, the autophagic, or the
      necrotic way; however, the mechanisms of sperm death are not clear. Here,
      ejaculated human spermatozoa were evaluated for apoptosis and reactive oxygen
      species production in the absence or presence of melatonin, and we concluded that
      melatonin reverses sperm apoptosis due to its free radical scavenging actions.

PMID- 20152968
TI  - Outcome and experience of implementing spinal muscular atrophy carrier screening
      on sperm donors.
AB  - Spinal muscular atrophy (SMA) carrier screening was performed on 277 active semen
      donors and new semen donor applicants; five men tested positive as carriers for
      SMA. The risk for specific medical problems in donor offspring can be
      significantly reduced by incorporating new genetic tests, such as spinal muscular
      atrophy carrier screening, into donor screening practices; however, future
      efforts should focus on communicating the limitations of genetic screening to
      donor gamete recipients and on the development of guidelines for implementing new
      genetic tests on donors.

PMID- 20152969
TI  - Three-dimensional geometric morphometric analysis of cranio-facial sexual
      dimorphism in a Central European sample of known sex.
AB  - This article presents an approach for estimating the sexual dimorphism of adult
      crania using three-dimensional geometric morphometric methods. The study sample
      consisted of 139 crania of known sex (73 males and 66 females) belonging to
      persons who lived during the first half of the 20th century in Bohemia. The three
      dimensional co-ordinates of 82 ecto-cranial landmarks and 39 semi-landmarks
      covering the midsagittal curve of the cranial vault were digitised using a
      MicroScribe G2X contact digitiser. The purposes of the investigation were to
      define the regions of the cranium where sexual dimorphism is most pronounced and
      to investigate the effectiveness of this method for determining sex from the
      shape of the cranium. The results demonstrate that it is better to analyse
      apportionable parts of the cranium rather than the cranium as a whole.
      Significant sexual differences (significance was determined using multivariate
      analysis of variance) were noted in the shape of the midsagittal curve of the
      vault, upper face, the region of the nose, orbits, and palate. No differences
      were recorded either in the shape of the cranium as a whole or in the regions of
      the base and the neurocranium. The greatest accuracy in determining sex was found
      in the region of the upper face (100% of study subjects correctly classified) and
      the midsagittal curve of the vault (99% of study subjects correctly classified).

PMID- 20152970
TI  - A case of postpartum pubic symphysis diastasis.

PMID- 20152971
TI  - Fertility and obstetric outcome after conservative management of placenta
      accreta.
AB  - OBJECTIVE: To determine the fertility and obstetric outcomes after conservative
      management of placenta accreta. METHODS: A retrospective observational cohort
      study of all identified cases of placenta accreta from 1993 to 2007 in 2 tertiary
      university hospitals in France. For patients treated conservatively, maternal and
      fetal morbidity, reproductive function, fertility, and subsequent pregnancies
      were recorded. RESULTS: During the study period, 46 patients were treated by
      conservative management; 6 patients underwent a secondary hysterectomy. Of the
      remaining 40 patients, 35 were followed up for a median of 65 months (range 18
      156 months). Patients resumed their menstrual cycles after a median of 130 days
      (range 48-176 days). Menses were irregular in 11 patients (31%), but none had
      amenorrhea. Twelve of the 14 patients desiring another pregnancy achieved a total
      of 15 pregnancies; 2 patients had recurrent placenta accreta. Five spontaneous
      abortions and 1 termination of pregnancy occurred during the first trimester. The
      median term at delivery was 37 weeks (range, 35-40 weeks). Four patients
      delivered prematurely. CONCLUSION: Conservative management of placenta accreta
      can preserve fertility, although the risk of recurrent placenta accreta appears
      to be high.

PMID- 20152972
TI  - Effect of continuous support during labor on duration of labor and rate of
      cesarean delivery.
AB  - OBJECTIVE: To evaluate the effect of continuous support provided by midwives
      during labor on the duration of the different stages of labor and the rate of
      cesarean delivery. METHOD: A randomized trial of 100 eligible nulliparous women
      who had not received education classes on childbirth. In the intervention group
      (n=50), continuous support during labor was provided; the control group (n=50)
      did not receive continuous support. RESULTS: The two groups did not differ by
      age, employment, educational level, gestational age, economic status, and
      neonatal weight. Mean duration of the active phase of labor (167.9+/-76.3 vs
      247.7+/-101 min, P<0.001), second stage of labor (34.9+/-25.4 vs 55.3+/-33.7 min,
      P=0.003), and the number of cesarean deliveries (4 vs 12, P=0.026) were
      significantly lower in the intervention group compared with the control group.
      The rates of oxytocin use and Apgar scores of less than 7 at 5 minutes were
      similar between the two groups. CONCLUSION: Continuous support provided by
      midwives during labor may reduce the duration of labor and the number of cesarean
      deliveries; this model of support should be available to all women.

PMID- 20152973
TI  - Evaluation of cervical visual inspection screening in Dar es Salaam, Tanzania.
AB  - OBJECTIVE: To evaluate the feasibility and performance of screening for cervical
      cancer using visual inspection with acetic acid (VIA) or with Lugol's iodine
      (VILI) in Dar es Salaam, Tanzania. METHODS: The accuracy of tests for detecting
      cervical intraepithelial neoplasia (CIN) was assessed in a cross-sectional study
      of 10378 women. All women who were screened underwent colposcopy, and biopsies
      were offered to those with abnormal colposcopy results. RESULTS: The positivity
      rates were 3.8% for VIA and 4.8% for VILI. The peak positivity rates for both
      visual tests were observed just after training or re-training and gradually
      declined thereafter. CIN 1 was diagnosed in 41 women, CIN 2-3 in 33 women, and
      invasive cancer in 200 women, showing high detection rates of invasive cancer.
      The sensitivity and specificity for the detection of CIN 2-3 lesions were 60.6%
      (95% confidence interval [CI], 42.1-77.1) and 98.2% (95% CI, 97.9-98.4),
      respectively, for VIA; and 93.9% (95% CI, 79.8-99.3) and 97.3% (95% CI, 97.0
      97.6), respectively, for VILI. Two-thirds of the women detected with CIN 2-3
      lesions were treated. CONCLUSION: Both visual screening tests are useful and
      accurate, especially in low-income settings. Standardization of assessment of the
      visual inspection techniques, continual training and supervision, and quality
      control measures are important for successful visual screening programs.

PMID- 20152974
TI  - Anal dilation during labor.
AB  - OBJECTIVE: To determine the incidence and range of anal dilation during the final
      phase of the second stage of labor and shortly after delivery; determine whether
      parity affects anal dilation; and obtain anthropometric data for future projects.
      METHODS: The anal diameter was measured on admission, when the fetal head
      crowned, and after suturing perineal injury in 142 women delivered between August
      2008 and May 2009 at University Hospital Pilsen and District Hospital Klatovy, in
      the Czech Republic. RESULTS: The anus was dilated during the second stage of
      labor in all women, and differences between primiparas and multiparas were not
      significant. The medians for both the anteroposterior and transverse diameters
      were 25 mm. No measured variable was statistically associated with anal sphincter
      dilation. CONCLUSION: Anal dilation during the second stage of labor causes
      anthropometric changes to the perineum. This ought to be considered when
      designing anthropometric studies and in studies aiming at minimizing anal
      sphincter trauma during delivery.

PMID- 20152975
TI  - Maternal gout associated with increased risk of low birth weight and preterm
      birth.

PMID- 20152976
TI  - Intrauterine device or estrogen treatment after hysteroscopic uterine septum
      resection.
AB  - OBJECTIVE: To investigate the effects on adhesion formation and pregnancy
      maintenance of an intrauterine device (IUD) and/or estrogen treatment after
      hysteroscopic septum resection. METHODS: After septum resection 100 women
      received either no treatment, or estrogens, or an IUD, or an IUD plus estrogens
      (n=25 per group). Most were later checked hysteroscopically for uterine cavity
      adhesions. All pregnancies occurring during the study period were recorded.
      RESULTS: Adhesions developed in 1 of 19 (5.3%) of the untreated women, 3 of 25
      (12%) of the women treated with an IUD plus estrogens, 2 of 19 (10.5%) of the
      women treated with an IUD only, and none of the women treated with estrogens
      only. None of the differences, however, were significant. Regarding pregnancy,
      the differences between groups were also not significant. CONCLUSION: Neither IUD
      placement, nor estrogen treatment, nor both were found to prevent intrauterine
      adhesions or facilitate pregnancy after hysteroscopic uterine septum resection.

PMID- 20152977
TI  - Seroprevalence of hepatitis B surface antigen among pregnant women in Jiangsu,
      China, 17 years after introduction of hepatitis B vaccine.
AB  - OBJECTIVE: To estimate the prevalence of hepatitis B surface antigen (HBsAg)
      among pregnant women in Jiangsu Province, eastern China, 17years after
      vaccination against hepatitis B virus (HBV) was introduced. METHODS: From August
      2002 to July 2004, serum samples from 6398 women between 15 and 20weeks of
      pregnancy and from 6 urban and 8 rural areas across Jiangsu Province were tested
      for markers of HBV. The results were then compared with the rates before 1980.
      RESULTS: The overall rates of 6.71% for HBsAg and 36.84% for anti-HBs were
      significantly lower and higher, respectively, than the prevaccination rates. The
      rate for HBsAg was lower in urban areas than in rural areas (5.75% vs 7.14%,
      P=0.04). Although the rate used to be much higher in the northern part of Jiangsu
      Province, which is less prosperous than the southern part, the rates are now
      similar in both parts (6.60% vs 6.97%). CONCLUSION: These findings demonstrate a
      drop in the prevalence of HBsAg among pregnant women in Jiangsu Province since
      the introduction of vaccination programs in 1980, and indicate that HBV infection
      can also be controlled in less prosperous areas.

PMID- 20152978
TI  - A qualitative study of the information needs of premenopausal women with breast
      cancer in terms of contraception, sexuality, early menopause, and fertility.
AB  - OBJECTIVES: To evaluate the information needed and received by premenopausal
      Turkish women with breast cancer regarding contraception, early menopause,
      infertility, fertility preservation, and sexuality. METHODS: A qualitative
      exploratory methodology was used whereby an interviewer met on 2 occasions with
      women with breast cancer. The participants-who were recruited from the oncology
      clinic of Adnan Menderes University Hospital, Aydin, Turkey-were premenopausal,
      younger than 50 years of age, and had been diagnosed with breast cancer within
      the past year. Raw data were sorted under themes. RESULTS: Premenopausal women
      with breast cancer received insufficient counseling on contraception, early
      menopause, infertility, fertility preservation, and sexuality, despite their
      willingness to receive information. CONCLUSION: In Turkey, premenopausal women
      with breast cancer should receive comprehensive information and counseling from
      oncology staff on the issues studied. The present study may guide future research
      on this topic.

PMID- 20152979
TI  - Array-CGH detection of UGT2B28 gene deletion in a girl with primary amenorrhea
      and hyperandrogenism.

PMID- 20152980
TI  - Peri-aortic fat, cardiovascular disease risk factors, and aortic calcification:
      the Framingham Heart Study.
AB  - OBJECTIVE: Perivascular fat through the secretion of paracrine and pro
      inflammatory mediators may play a role in obesity-mediated vascular disease. We
      sought to examine associations between adipose tissue depots immediately
      surrounding the thoracic aorta, metabolic risk factors, and vascular
      calcification. METHODS: In participants free of cardiovascular disease (CVD) from
      the Framingham Heart Study Offspring cohort who underwent computed tomography
      (n=1067, mean age 59 years, 56.1% women), thoracic peri-aortic fat depots were
      quantified. Visceral abdominal tissue (VAT) and calcification of the thoracic and
      abdominal aorta were also measured. RESULTS: Peri-aortic fat depots were
      correlated with body mass index, waist circumference (WC), VAT (all p<0.0001),
      hypertension (p=0.007), low HDL (p<0.0001), serum triglycerides (p<0.0001),
      impaired fasting glucose (p=0.005), and diabetes (p=0.02). These associations
      generally remained significant after adjustment for BMI and WC (all p
      values<0.05), but not after VAT adjustment. Thoracic aortic fat was associated
      with thoracic calcification in models containing VAT (OR 1.31, 95% CI 1.01-1.71,
      p=0.04), but was not significant after adjustment for CVD risk factors (OR 1.16,
      95% CI 0.88-1.51, p=0.30). Thoracic aortic fat, however, was associated with
      abdominal aortic calcification (OR 1.48, 95% CI 1.11-1.98, p=0.008) and coronary
      artery calcification (OR 1.47, 95% CI 1.09-1.98, p=0.001) even in models
      including CVD risk factors and VAT. CONCLUSIONS: Thoracic peri-aortic fat is
      associated with measures of adiposity, metabolic risk factors, and coronary and
      abdominal aortic calcification.

PMID- 20152981
TI  - Elevated heart rate and cardiovascular outcomes in patients with coronary artery
      disease: clinical evidence and pathophysiological mechanisms.
AB  - There is an established body of evidence from epidemiological studies which
      indicates that an elevated resting heart rate is independently associated with
      atherosclerosis and increased cardiovascular morbidity and mortality, in both the
      general population and in patients with established cardiovascular disease.
      Clinical trial data suggest that in patients with coronary artery disease, an
      elevated heart rate identifies those at increased risk of adverse cardiovascular
      outcomes, and that lowering of heart rate may reduce major cardiovascular events
      in patients with an elevated heart rate and symptom-limiting angina. These
      results suggest that an increased heart rate may have an adverse impact on the
      atherosclerotic process and increase the risk of a cardiovascular event in
      patients with coronary artery disease. The precise pathophysiological mechanisms
      that link heart rate and cardiovascular outcomes have yet to be defined.
      Possibilities may include indirect mechanisms related to autonomic dysregulation
      and those due to an increase in heart rate per se, which can increase the
      ischaemic burden and exert local haemodynamic forces that can adversely impact on
      the endothelium and arterial wall. For these reasons, heart rate should be
      considered as a therapeutic target in the treatment of patients with coronary
      artery disease.

PMID- 20152982
TI  - Identification of rupture locations in patient-specific abdominal aortic
      aneurysms using experimental and computational techniques.
AB  - In the event of abdominal aortic aneurysm (AAA) rupture, the outcome is often
      death. This paper aims to experimentally identify the rupture locations of in
      vitro AAA models and validate these rupture sites using finite element analysis
      (FEA). Silicone rubber AAA models were manufactured using two different materials
      (Sylgard 160 and Sylgard 170, Dow Corning) and imaged using computed tomography
      (CT). Experimental models were inflated until rupture with high speed photography
      used to capture the site of rupture. 3D reconstructions from CT scans and
      subsequent FEA of these models enabled the wall stress and wall thickness to be
      determined for each of the geometries. Experimental models ruptured at regions of
      inflection, not at regions of maximum diameter. Rupture pressures (mean+/-SD) for
      the Sylgard 160 and Sylgard 170 models were 650.6+/-195.1mmHg and 410.7+/
      159.9mmHg, respectively. Computational models accurately predicted the locations
      of rupture. Peak wall stress for the Sylgard 160 and Sylgard 170 models was
      2.15+/-0.26MPa at an internal pressure of 650mmHg and 1.69+/-0.38MPa at an
      internal pressure of 410mmHg, respectively. Mean wall thickness of all models was
      2.19+/-0.40mm, with a mean wall thickness at the location of rupture of 1.85+/
      0.33 and 1.71+/-0.29mm for the Sylgard 160 and Sylgard 170 materials,
      respectively. Rupture occurred at the location of peak stress in 80% (16/20) of
      cases and at high stress regions but not peak stress in 10% (2/20) of cases. 10%
      (2/20) of models had defects in the AAA wall which moved the rupture location
      away from regions of elevated stress. The results presented may further
      contribute to the understanding of AAA biomechanics and ultimately AAA rupture
      prediction.

PMID- 20152983
TI  - Development and validation of ultrasound speckle tracking to quantify tendon
      displacement.
AB  - Ultrasound can be used to study tendon movement. However, measurement of tendon
      movement is mostly based on manual tracking of anatomical landmarks such as the
      musculo-tendinous junction, limiting the applicability to a small number of
      muscle-tendon units. The aim of this study was to quantify tendon displacement
      without anatomical landmarks using a speckle tracking algorithm optimized for
      tendons in long B-mode image sequences. A dedicated two-dimensional multi-kernel
      block-matching scheme with subpixel motion estimation was devised to handle large
      displacements over long sequences. The accuracy of the tracking on porcine
      tendons was evaluated during different displacements and velocities.
      Subsequently, the accuracy of tracking the flexor digitorum superficialis (FDS)
      of a human cadaver hand was evaluated. Finally, the in-vivo accuracy of the
      tendon tracking was determined by measuring the movement of the FDS at the wrist
      level. For the porcine experiment and the human cadaver arm experiment tracking
      errors were, on average, 0.08 and 0.05mm, respectively (1.3% and 1.0%). For the
      in-vivo experiment the tracking error was, on average, 0.3mm (1.6%). This study
      demonstrated that our dedicated speckle tracking can quantify tendon displacement
      at different physiological velocities without anatomical landmarks with high
      accuracy. The technique allows tracking over large displacements and in a wider
      range of tendons than by using anatomical landmarks.

PMID- 20152985
TI  - ZnO nanoparticle-containing emulsions for transparent, hydrophobic UV-absorbent
      films.
AB  - A simple method for the preparation of thin, zinc oxide nanoparticle-containing
      films showing high UV absorption, high transmittance in the visible range (>88%),
      and water repellence with contact angles of 120 degrees is presented. The films
      are coated from an emulsion containing the hydrophobic polymer and the
      nanoparticles. This emulsion was prepared by mixing commercial o/w emulsions used
      for hydrophobic coatings on textiles with ZnO nanoparticle-containing o/w
      emulsions. The latter were designed so that the mixed coating formulation could
      be prepared without breaking. Preparation and properties of the o/w emulsions as
      well as the final films are elaborated. The performance of hydrophobic and
      hydrophilic ZnO nanoparticles during preparation and in the final film is
      evaluated.

PMID- 20152984
TI  - The facile synthesis of an aldehyde-containing graft copolymer membrane for
      covalent protein capture with retention of protein functionality.
AB  - The immobilization of biomolecules onto an insoluble carrier surface has always
      been a subject of great interest to enhance their resistance to pH and
      temperature, which aids in an increased activity lifespan as well as easy reuse
      of the said biomolecules. However, traditional methods are only able to provide
      single-layer biomolecular binding and require multiple chemical reactions to
      prepare the final substrate before the immobilization can be carried out
      properly. Here we report a facile one-step chemical synthesis of a new aldehyde
      bearing graft copolymer via atom transfer radical polymerization (ATRP) for
      covalent protein capture in a multilayered approach to covalently capture bovine
      serum albumin (BSA) onto a polymeric membrane. The resultant protein-bound
      membrane illustrated the retention of BSA's stereoselective discrimination
      ability by binding to an excess of 2 mol of tryptophan/mol of BSA and
      demonstrated an enantioresolution of a 0.184 mM racemic tryptophan mixture with a
      time-averaged-separation factor of 2.9.

PMID- 20152986
TI  - A new modified parachor model for predicting surface compositions of binary
      liquid mixtures. On the importance of surface volume representation.
AB  - Differences in composition between the surface region and the bulk region for
      binary liquids can occur due to preferential adsorption, and such surface
      enrichment can influence mass and heat transport across the interface. In order
      to investigate surface enrichment, reliable methods for predicting surface
      compositions are required. In this study, an approach based on a modified
      parachor model is developed in order to provide a generally more accurate
      prediction for the surface composition. In contrast to other predictive models, a
      more "realistic" surface volume representation is considered. This model is
      subsequently utilized to predict the surface compositions of several binary
      systems, involving organic-aqueous, organic-organic and aneotropic mixtures. The
      surface compositions obtained are compared to those directly determined from
      experimental measurements, if any, and to those calculated using other predictive
      models. The results show that the present modified parachor model provides
      surface composition predictions which are equal to, and in some cases are better
      than (particularly for aneotropic mixtures), those provided by other models. In
      general, the results demonstrate the usefulness of including a "real" surface
      volume approximation in the surface enrichment calculations.

PMID- 20152987
TI  - A novel multi-responsive polyampholyte composite hydrogel with excellent
      mechanical strength and rapid shrinking rate.
AB  - Series of hydrophilic core-shell microgels with cross-linked poly(N
      isopropylacrylamide) (PNIPAAm) as core and poly(vinyl amine) (PVAm) as shell are
      synthesized via surfactant-free emulsion polymerization. Then, the microgels are
      treated with a small amount of potassium persulfate (KPS) to generate free
      radicals on the amine nitrogens of PVAm, which subsequently initiate the graft
      copolymerization of acrylic acid (AA), acryloyloxyethyl trimethyl ammonium
      chloride (DAC), and acrylamide (AAm) onto microgels to prepare multi-responsive
      composite hydrogels. The composite hydrogels consist of cross-linked ungrafted
      polyampholyte chains as the first network and microgels with grafted
      polyampholyte chains as graft point and second network and show surprising
      mechanical strength and rapid response rate. The investigation shows the compress
      strength of composite hydrogels is up to 17-30 MPa, which is 60-100 times higher
      than that of the hydrogel matrix. The composite hydrogel shows reversible switch
      of transmittance when traveling the lowest critical temperature (LCST) of
      microgels. When the composite hydrogel swollen in pH 2.86 solution at ambient
      condition is immersed into the pH 7.00 solution at 45  degrees C, a rapid dynamic
      shrinking can be observed. And the character time (tau) of shrinking dynamic of
      composite hydrogel is 251.9 min, which is less than that of hydrogel matrix
      (tau=2273.7 min).

PMID- 20152988
TI  - Preparation of Span 80/oil/water highly concentrated emulsions: influence of
      composition and formation variables and scale-up.
AB  - The influence of composition and preparation variables on the properties of W/O
      highly concentrated emulsions obtained in the system Span 80/oil/water was
      studied. Emulsions prepared with decane, dodecane and hexadecane were analysed.
      Stability of emulsions was found to depend on the oil as follows: stability of
      hexadecane emulsions > dodecane > decane. It was attributed to the lower
      solubility of water in the oil with longer chain. Experimental design tools were
      used to study the influence of composition and preparation variables and scale-up
      on the droplet size and polydispersity of emulsions formed. The most important
      factor was found to be the surfactant-oil ratio, SO, as more surfactant could
      stabilize more interface, but other preparation variables, like mixing rate,
      omega, were also found to influence the droplet size and polydispersity. The
      proper scale-up variables were found not to correspond to the dimensionless
      variables commonly used in scale-up studies, but total addition time, t(t), and
      angular mixing velocity, omega, seemed to be the proper ones.

PMID- 20152989
TI  - Exchange-dynamics of a neutral hydrophobic dye in micellar solutions studied by
      Fluorescence Correlation Spectroscopy.
AB  - The dynamics of the exchange of the moderately hydrophobic neutral dye Coumarine
      152 between the aqueous phase and the phase formed by neutral Triton X-100
      micelles is studied by Fluorescence Correlation Spectroscopy. The changes in the
      photophysical properties of the dye in presence of the micelles are discussed.
      The low quantum yield, the low saturation threshold and the necessary high
      energetic excitation of this dye requires a careful selection of the experimental
      conditions in order to obtain dynamic and diffusional properties with reasonable
      precision. It is shown that the contrast between the brightness of free and bound
      dye has a strong influence on the sensitivity of the FCS experiment. The entry
      rate constant of the dye to the micelles, k(+)=(0.8+/-0.3)*10(10) M(-1) s(-1), is
      very near to the diffusion controlled limit. The high association equilibrium
      constant of K=(129+/-3)*10(3) M(-1) is mainly determined by the low exit rate
      constant, k(-)=(0.6+/-0.2)*10(5) s(-1).

PMID- 20152990
TI  - Morphophonological salience as a compensatory means for deficits in the
      acquisition of past tense in SLI.
AB  - The aim of this study is threefold: Firstly, to describe the acquisition patterns
      of Greek past tense by children with specific language impairment (SLI);
      secondly, to investigate the relationship between the phonological salience of
      past tense in Greek and its acquisition by children of typical and atypical
      language development; thirdly, to establish an account on the nature of specific
      language impairment by comparing the acquisition patterns exhibited by children
      with SLI to those presented by typically developing children. The performance of
      10 children with SLI in elicited past tense production is compared to that of
      chronological age matched (CA) and language matched (LM) controls. Based on the
      claim that morphophonological salience aids acquisition (or learning), it is
      predicted that children with SLI will perform better in the production of past
      forms of higher salience than less salient forms. The results confirm this
      prediction, providing support for the claim that salience differences do account
      for better performances in tense marking in Greek SLI. LEARNING OUTCOMES: By
      reading this article, the reader will be able to: (1) describe the problems
      children with SLI face in Greek tense marking, (2) explain the reasons why SLI
      performances differ from one language to the next based on the Interpretability
      Hypothesis, (3) discuss whether children with SLI differ qualitatively from TD
      controls in past tense marking and explain how.

PMID- 20152991
TI  - Association between peanut allergy and asthma morbidity.
AB  - OBJECTIVE: To evaluate the relationship between peanut allergy and asthma
      morbidity in school-age children. STUDY DESIGN: The study involved a medical
      chart review to assess the association of peanut allergy with asthma morbidity in
      children beyond age 3 years. Peanut allergy was assessed by specific and
      validated criteria. A Poisson regression model was used to compare the frequency
      of systemic steroid use and of hospitalization for asthma beyond age 3 years in
      children with asthma with and without peanut allergy. RESULTS: Children with
      peanut allergy had a 2.32-times greater rate of hospitalization (P = .03) and a
      1.59-times greater rate of systemic steroid use (P <.001) after controlling for
      covariates. CONCLUSIONS: Peanut allergy serves as an early marker for asthma
      morbidity. Early prevention and intervention can improve quality of care.

PMID- 20152992
TI  - Predictors of low cardiac output syndrome after isolated mitral valve surgery.
AB  - BACKGROUND: Low cardiac output syndrome is defined as the need for a
      postoperative intra-aortic balloon pump or inotropic support for longer than 30
      minutes in the intensive care unit. Mitral valve surgery is increasingly being
      performed in high-risk patients who might require mechanical circulatory support
      for low cardiac output syndrome. Therefore the aim of this study was to identify
      the preoperative predictors of low cardiac output syndrome after mitral valve
      surgery. METHODS: We conducted a retrospective review of data prospectively
      entered into an institutional database. Between 1990 and February 2008, 3039
      patients underwent isolated mitral valve surgery with or without coronary bypass
      surgery. The independent predictors of low cardiac output syndrome and operative
      mortality were determined by means of stepwise logistic regression analysis.
      RESULTS: The overall prevalence of low cardiac output syndrome was 7%. The
      independent predictors of low cardiac output syndrome were urgency of the
      operation (odds ratio, 2.9), earlier year of operation (odds ratio, 2.4), left
      ventricular ejection fraction of less than 40% (odds ratio, 2.1), New York Heart
      Association class IV (odds ratio, 2), body surface area of 1.7 m(2) or less (odds
      ratio, 1.6), ischemic mitral valve pathology (odds ratio, 1.6), and
      cardiopulmonary bypass time (odds ratio, 1.02). The operative mortality was
      higher in patients with low cardiac output syndrome (30% vs 1.3%, P < .001).
      Overall operative mortality was 3.4%. The independent predictors of mortality
      were urgency of the operation (odds ratio, 7.1), renal failure (odds ratio, 4.3),
      nonuse of polytetrafluoroethylene sutures (Gore-Tex; W. L. Gore & Associates,
      Inc, Austin, Tex; odds ratio, 2.1), any reoperative surgical intervention (odds
      ratio, 1.8), increasing age (odds ratio, 1.03), and cardiopulmonary bypass time
      (odds ratio, 1.02). CONCLUSIONS: Low cardiac output syndrome is associated with
      significantly increased morbidity and mortality. Novel strategies to preserve
      renal function, optimization of pre-existing heart failure symptoms, and use of
      artificial polytetrafluoroethylene sutures might reduce the incidence of low
      cardiac output syndrome and lead to improved results after mitral valve surgery.

PMID- 20152993
TI  - Salmonella: the forgotten pathogen: health hazards of compliance with European
      bathing water legislation.
AB  - The increasing demands on recreational waters have made microbial contamination a
      matter of public and scientific concern. This study aimed to search for
      Salmonella spp. in waters classified according EU Directive 2006/7/EC, in order
      to assess associations between its prevalence and the concentration of the non
      pathogenic new faecal indicators: Escherichia coli and intestinal enterococci.
      Although a statistically significant association was observed Salmonella was
      detected on beaches classified as "Good" (9.3%) and "Excellent" (14.4%) which
      compromises the idea that faecal indicators can be predictors of pathogens.
      Attending the high prevalence of Salmonella found (23.1%) it seemed important to
      improve the efficiency of the conventional analytical method (ISO 6340:1995),
      comparing its draft with SML-VIDAS Salmonella and two new chromogenic media: AES
      Salmonella Agar Plate (ASAP) and Simple Method Salmonella (SMS). ASAP showed the
      higher efficiency and can be recommended for a faster detection and presumptive
      identification of salmonellae in bathing waters.

PMID- 20152994
TI  - Metals and nutrients in the Severn Estuary and Bristol Channel: contemporary
      inputs and distributions.
AB  - The contemporary inputs of total metals to the Severn Estuary and the inner
      Bristol Channel from land-based sources have declined over the past 25 years,
      with the possible exception of chromium. Coherent measurements of dissolved and
      suspended particulate and sedimentary metals, dissolved nutrients and master
      variables, including salinity, suspended particulate matter (SPM) concentration,
      dissolved oxygen saturation and chlorophyll concentration, were made in the
      Severn Estuary and inner Bristol Channel during 2004 and 2005. Concentrations of
      total inorganic nitrogen (TIN) were comparable with values reported 20 years ago
      but were dominated by nitrate, possibly from diffuse sources. Sediments had total
      metal concentrations similar to the World averages for riverine particulate
      material, except for Cu which had elevated values in 2004. Concentrations of
      suspended particulate As, Cr and Zn showed little spatial variability. Dissolved
      concentrations of most metals were generally below their respective environmental
      quality standards, although high concentrations of dissolved Cu, and possibly As,
      appeared to be emanting from a sedimentary source. The K(D)s for As, Cr, Cu and
      Zn displayed an inverse relationship with SPM concentration, whereas the K(D)s
      for Hg increased with SPM. The results show that there is a need for a sediment
      inventory of metals to account for metal release during sediment resuspension
      events.

PMID- 20152995
TI  - Assessing underwater noise levels during pile-driving at an offshore windfarm and
      its potential effects on marine mammals.
AB  - Marine renewable developments have raised concerns over impacts of underwater
      noise on marine species, particularly from pile-driving for wind turbines.
      Environmental assessments typically use generic sound propagation models, but
      empirical tests of these models are lacking. In 2006, two 5MW wind turbines were
      installed off NE Scotland. The turbines were in deep (>40m) water, 25km from the
      Moray Firth Special Area of Conservation (SAC), potentially affecting a protected
      population of bottlenose dolphins. We measured pile-driving noise at distances of
      0.1 (maximum broadband peak to peak sound level 205dB re 1microPa) to 80km (no
      longer distinguishable above background noise). These sound levels were related
      to noise exposure criteria for marine mammals to assess possible effects. For
      bottlenose dolphins, auditory injury would only have occurred within 100m of the
      pile-driving and behavioural disturbance, defined as modifications in behaviour,
      could have occurred up to 50km away.

PMID- 20152996
TI  - [Which of the anthropometric measures to define excess weight is the best
      discriminator of cardiovascular risk?].

PMID- 20152997
TI  - [The CRB-65 scale in pneumonia in the elderly].

PMID- 20152998
TI  - Addition of metformin to exogenous glucagon-like peptide-1 results in increased
      serum glucagon-like peptide-1 concentrations and greater glucose lowering in type
      2 diabetes mellitus.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone that lowers blood glucose
      after meals in type 2 diabetes mellitus. The therapeutic potential of GLP-1 in
      diabetes is limited by rapid inactivation by the enzyme dipeptidylpeptidase-4
      (DPP-4). Metformin has been reported to inhibit DPP-4. Here we investigated the
      acute effects of metformin and GLP-1 alone or in combination on plasma DPP-4
      activity, active GLP-1 concentrations, and glucose lowering in type 2 diabetes
      mellitus. Ten subjects with type 2 diabetes mellitus (8 male and 2 female; age,
      68.7 +/- 2.6 years [mean +/- SEM]; body mass index, 29.6 +/- 1.7 kg/m2;
      hemoglobin A(1c), 7.0% +/- 0.1%) received 1 of 3 combinations after an overnight
      fast in a randomized crossover design: metformin 1 g orally plus subcutaneous
      injection saline (Metformin), GLP-1 (1.5 nmol/kg body weight subcutaneously) plus
      placebo tablet (GLP-1), or metformin 1 g plus GLP-1(Metformin + GLP-1). At 15
      minutes, glucose was raised to 15 mmol/L by rapid intravenous infusion of
      glucose; and responses were assessed over the next 3 hours. This stimulus does
      not activate the enteroinsular axis and secretion of endogenous GLP-1, enabling
      the effect of exogenously administered GLP-1 to be examined. Mean area under
      curve (AUC) (0-180 minutes) plasma glucose responses were lowest after Metformin
      + GLP-1 (mean +/- SEM, 1629 +/- 90 mmol/[L min]) compared with GLP-1 (1885 +/- 86
      mmol/[L min], P < .002) and Metformin (2045 +/- 115 mmol/[L min], P < .001). Mean
      AUC serum insulin responses were similar after either Metformin + GLP-1 (5426 +/-
      498 mU/[L min]) or GLP-1 (5655 +/- 854 mU/[L min]) treatment, and both were
      higher than Metformin (3521 +/- 410 mU/[L min]; P < .001 and P < .05,
      respectively). Mean AUC for plasma DPP-4 activity was lower after Metformin + GLP
      1 (1505 +/- 2 MUmol/[mL min], P < .001) and Metformin (1508 +/- 2 MUmol/[mL min],
      P < .002) compared with GLP-1 (1587 +/- 3 MUmol/[mL min]). Mean AUC measures for
      plasma active GLP-1 concentrations were higher after Metformin + GLP-1 (820 x 104
      +/- 51 x 104 pmol/[L min]) compared with GLP-1 (484 x 104 +/- 31 x 104 pmol/[L
      min], P < .001) and Metformin (419 * 104 +/- 34 x 104 pmol/[L min], P < .001),
      respectively. In patients with type 2 diabetes mellitus, metformin inhibits DPP-4
      activity and thus increases active GLP-1 concentrations after subcutaneous
      injection. In combination with GLP-1, metformin significantly lowers plasma
      glucose concentrations in type 2 diabetes mellitus subjects compared with GLP-1
      alone, whereas insulin responses were similar. Metformin enhances serum
      concentrations of injected active GLP-1(7-36)amide, and the combination results
      in added glucose-lowering potency.

PMID- 20152999
TI  - The effect of genetic variability on the correlation between blood glucose and
      glycated hemoglobin levels.
AB  - The disturbing results of recent clinical trials aimed to control cardiovascular
      risk of diabetes by aggressive control of blood glucose prompted us to analyze
      the effect of genetic variability of 2 polymorphic enzymes abundant in red blood
      cells on the correlation between blood glucose and glycated hemoglobin (Hb). Two
      hundred eighty subjects with type 2 diabetes mellitus were studied. Adenylate
      kinase locus 1 (AK1) and acid phosphatase locus 1 were determined. Correlation
      between blood glucose and glycated Hb was determined for phenotypes of the 2
      systems. The correlation between blood glucose and glycated Hb is higher in
      carriers of AK1*2 allele than in subjects with AK11 phenotype. The highest
      coefficient is observed in acid phosphatase locus 1 phenotypes with the highest
      enzymatic activity; and the lowest, in phenotypes with the lowest activity.
      Effects of sex, blood glucose level, age, age at onset, and duration of disease
      have been also considered. Our data are in agreement with recent observation in
      healthy subjects suggesting a role of genetic factors on glycated Hb level. If
      glycation of structural and functional protein is dependent not only on blood
      glucose level but also on genetic factors, these factors could have an important
      role in the susceptibility and clinical course of diabetes.

PMID- 20153000
TI  - Regression of preestablished cholesterol gallstones by dietary garlic and onion
      in experimental mice.
AB  - We have recently reported the health beneficial potential of dietary garlic and
      onion in reducing the incidence and severity of cholesterol gallstone (CGS)
      during its experimental induction in mice. In the current study, the efficacy of
      dietary garlic and onion in regressing preestablished CGS was investigated in
      experimental mice. After inducing CGS in mice with a lithogenic diet for 10
      weeks, they were maintained on basal diets containing 0.6% dehydrated garlic or
      2% dehydrated onion for a further 10 weeks. Dietary garlic and onion, either raw
      or heat processed, regressed preformed CGS in mice up to 53% to 59%, whereas the
      regression in the basal control diet group was only 10%. The antilithogenic
      potency of garlic was decreased by its heat processing, but not in the case of
      onion. Biliary cholesterol was significantly decreased in garlic- and onion-fed
      animals. Biliary cholesterol saturation index and hydrophobicity index were
      significantly lowered by dietary garlic and onion. Serum and liver cholesterol
      levels were decreased by feeding these spices during post-CGS induction period.
      Hepatic hydroxymethylglutaryl-coenzyme A reductase activity was increased after
      feeding garlic and onion, whereas activities of the cholesterol-degrading enzymes
      cholesterol-7alpha-hydroxylase and sterol-27-hydroxylase were increased in spice
      fed groups. These results indicate that feeding garlic and onion effectively
      accelerates the regression of preformed CGS by promoting cholesterol desaturation
      in bile. This observation is significant in the context of evolving dietary
      intervention strategy to address regression of existing CGS and stopping the
      possible recurrence.

PMID- 20153001
TI  - Beneficial effects of IH-901 on glucose and lipid metabolisms via activating
      adenosine monophosphate-activated protein kinase and phosphatidylinositol-3
      kinase pathways.
AB  - IH-901 is an intestinal metabolite of ginsenosides found in Panax ginseng. In the
      present study, effects of IH-901 on glucose and lipid metabolisms were examined
      using C2C12 myotubes and C57BL/ksJ db/db mice. A significant increase in
      phosphorylated adenosine monophosphate-activated protein kinase was observed when
      differentiated C2C12 myotubes were treated with IH-901. Glucose transporter 4
      protein expressions were also up-regulated when muscle cells were treated with of
      IH-901 up to 60 minutes, resulting in stimulation of glucose uptake by 25% as
      compared with untreated cells. In addition, phosphatidylinositol-3 kinase and Akt
      protein expressions were increased when C2C12 myotubes were exposed to IH-901 for
      up to 3 hours; and these effects including glucose uptake were attenuated by
      pretreatment with LY294002, a selective phosphatidylinositol-3 kinase inhibitor.
      In animal study, IH-901 at 25 mg/kg lowered the plasma glucose, triglyceride,
      cholesterol, and nonesterified fatty acid levels by 20.7%, 41.6%, 20.2%, and
      24.6%, respectively, compared with control mice. In the meantime, plasma insulin
      levels were significantly increased by 2.2 and 3.4 times in 10 and 25 mg/kg
      treated mice, respectively, compared with control mice, in parallel with the
      histologic observation showing a preserved architecture of the pancreatic islet.
      Protein and gene expression patterns for adenosine monophosphate-activated
      protein kinase, sterol regulatory element binding protein-1a, and glucose
      transporter 4 in the liver and skeletal muscles were similar to those in cell
      studies. In summary, IH-901 might be a promising therapeutic agent improving
      altered glucose and lipid metabolisms revealed in type 2 diabetes mellitus
      patients.

PMID- 20153002
TI  - Dissociated effects of glucose-dependent insulinotropic polypeptide vs glucagon
      like peptide-1 on beta-cell secretion and insulin clearance in mice.
AB  - Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide
      (GIP) potently augment insulin response to glucose. It is less known what their
      effects are insulin clearance, which also contributes to peripheral
      hyperinsulinemia observed after administration of incretins together with
      glucose. The aims of this study were the quantification of C-peptide secretion
      and the evaluation of insulin clearance after administration of GIP with glucose.
      This allows the assessment of GIP's effects on hyperinsulinemia. In addition,
      GIP's effects were compared with those of GLP-1. Anesthetized female NMRI mice
      were injected intravenously with glucose alone (1 g/kg, n = 35) or glucose
      together with GIP (50 microg/kg, n = 12). Samples were taken through the
      following 50 minutes, and C-peptide and insulin concentrations were used to
      reconstruct C-peptide secretion rate and insulin clearance. In a previous study,
      GLP-1 (10 microg/kg) was used in 12 mice; and we used those GLP-1 results to
      compare GIP effects with those of GLP-1. C-peptide secretion rate peaked at 1
      minute after glucose injection, and the immediate part of the insulin-releasing
      process was markedly augmented by both incretin hormones (1-minute suprabasal
      increment secretory rate was 20 +/- 2 pmol/min for GIP and 28 +/- 2 pmol/min for
      GLP-1, vs only 9 +/- 1 pmol/min for glucose alone; P < .001). Until 10 minutes
      after administration, C-peptide secretion remained higher with incretins (P <
      .0001), whereas starting from 20 minutes, the 3 patterns were undistinguishable
      (P > .2). Insulin clearance, previously shown to be abridged by 46% with GLP-1,
      was reduced only by a nonsignificant (P = .27) 21% with GIP. This study thus
      shows that the 2 incretins markedly augment glucose-stimulated insulin secretion
      in mice by a preferential action on the immediate response to glucose of insulin
      secretion. However, the action of GIP is less effective than that of GLP-1.
      Insulin clearance with GIP is not significantly reduced. We conclude that GIP is
      less potent than GLP-1 in inducing glucose-stimulated hyperinsulinemia in the
      mouse.

PMID- 20153003
TI  - Changes in alpha-glucosidase activities along the jejunal-ileal axis of normal
      rats by the alpha-glucosidase inhibitor miglitol.
AB  - Miglitol, an alpha-glucosidase inhibitor that inhibits postprandial hyperglycemia
      by delaying carbohydrate digestion and absorption along the jejunal-ileal axis,
      has recently been approved for use in patients with type 2 diabetes mellitus.
      Miglitol treatment may lead to increased alpha-glucosidase activities toward the
      ileum because carbohydrate flow toward the ileum increases. However, it is not
      yet known if miglitol treatment alters the alpha-glucosidase activities along the
      jejunal-ileal axis. In this study, we examined the effects of miglitol
      supplementation for 3 or 7 days on alpha-glucosidase activities along the jejunal
      ileal axis of Wistar rats. Supplementation with miglitol for 3 or 7 days in rats
      increased tissue weights of the lower jejunum and ileum, but did not alter tissue
      weights of the upper jejunum and cecum or the contents of the cecum. Furthermore,
      supplementation with miglitol for 7 days reduced the activities of isomaltase and
      maltase in the upper jejunum and increased the activities of sucrase, isomaltase,
      and maltase in the lower jejunum and ileum. These results suggest that the delay
      in carbohydrate digestion and absorption along the jejunal-ileal axis by miglitol
      supplementation in rats is associated with increased alpha-glucosidase activities
      toward the ileum.

PMID- 20153004
TI  - Glycosylphosphatidylinositol-specific phospholipase D improves glucose tolerance.
AB  - Insulin regulation of energy metabolism is complex and involves numerous
      signaling cascades. Insulin has been suggested to stimulate a phospholipase that
      cleaves glycosylphosphatidylinositols resulting in the generation of an inositol
      glycan that serves as an insulin mediator. To determine if
      glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) may play a role
      in glucose metabolism, we examined the effect of overexpressing GPI-PLD using
      adenovirus-mediated gene transfer in C57BL/6 mice. Overexpressing GPI-PLD was
      associated with a decrease in fasting glucose as well as an improvement in
      glucose tolerance as determined by an intraperitoneal glucose tolerance test.
      This effect to improve glucose tolerance does not result from an increase in
      insulin sensitivity, as overexpressing GPI-PLD does not alter the response to
      insulin. In contrast, the insulin response during the glucose tolerance test in
      GPI-PLD-overexpressing mice was increased. Overexpressing GPI-PLD in an
      insulinoma cell line enhanced glucose-stimulated insulin secretion, suggesting
      that enhanced insulin secretion in vivo may have contributed to the improved
      glucose tolerance.

PMID- 20153005
TI  - Dipeptidyl peptidase IV in the hypothalamus and hippocampus of monosodium
      glutamate obese and food-deprived rats.
AB  - Proline-specific dipeptidyl peptidases are emerging as a protease family with
      important roles in the regulation of signaling by peptide hormones related to
      energy balance. The treatment of neonatal rats with monosodium glutamate (MSG) is
      known to produce a selective damage on the arcuate nucleus with development of
      obesity. This study investigates the relationship among dipeptidyl peptidase IV
      (DPPIV) hydrolyzing activity, CD26 protein, fasting, and MSG model of obesity in
      2 areas of the central nervous system. Dipeptidyl peptidase IV and CD26 were,
      respectively, evaluated by fluorometry, and enzyme-linked immunosorbent assay and
      reverse transcriptase polymerase chain reaction in soluble (SF) and membrane
      bound (MF) fractions from the hypothalamus and hippocampus of MSG-treated and
      normal rats, submitted or not to food deprivation (FD). Dipeptidyl peptidase IV
      in both areas was distinguished kinetically as insensitive (DI) and sensitive
      (DS) to diprotin A. Compared with the controls, MSG and/or FD decreased the
      activity of DPPIV-DI in the SF and MF from the hypothalamus, as well as the
      activity of DPPIV-DS in the SF from the hypothalamus and in the MF from the
      hippocampus. Monosodium glutamate and/or FD increased the activity of DPPIV-DI in
      the MF from the hippocampus. The monoclonal protein expression of membrane CD26
      by enzyme-linked immunosorbent assay decreased in the hypothalamus and increased
      in the hippocampus of MSG and/or FD relative to the controls. The existence of
      DPPIV-like activity with different sensitivities to diprotin A and the identity
      of insensitive with CD26 were demonstrated for the first time in the central
      nervous system. Data also demonstrated the involvement of DPPIV-DI/CD26
      hydrolyzing activity in the energy balance probably through the regulation of
      neuropeptide Y and beta-endorphin levels in the hypothalamus and hippocampus.

PMID- 20153006
TI  - Increased financial accessibility and targeted education messages could increase
      ownership and use of mosquito nets in Purulia District, West Bengal, India.
AB  - Insecticide-treated mosquito nets are effective in reducing malaria transmission
      and mortality, yet they are underused for prevention. In this study, 561
      households in 33 clusters were surveyed to estimate the coverage of net ownership
      and the frequency of use according to selected characteristics. Of the 540
      participating household heads, 247 (46%) owned mosquito nets. Of 1681 individuals
      in households with mosquito nets, 1359 (81%) used the nets. A household monthly
      income > or =2000 Indian rupees (US$45) was strongly associated with mosquito net
      ownership (prevalence ratio=12, 95% CI 7.8-82). Factors independently associated
      with net use in multivariate analysis included age < 35 years (P<0.001), sleeping
      inside (P<0.001), use of repellent (P=0.03) as well as knowledge that mosquitoes
      cause malaria (P=0.002) and that malaria is severe in children (P<0.001). Whilst
      household income is the strongest determinant of mosquito net ownership, selected
      knowledge elements are associated with net use. It is necessary to improve
      financial accessibility to nets and to communicate that malaria is a disease
      transmitted by mosquitoes that could be fatal in children.

PMID- 20153007
TI  - Results of cryopreserved parathyroid autografts: a retrospective multicenter
      study.
AB  - BACKGROUND: The functionality of cryopreserved parathyroid autotransplantation
      (CPAT) has been evaluated in few studies, mostly conducted by experienced single
      institution centers that have reported different success rates ranging from 17%
      to 83%. In France, CPAT are rare and their functionality has never been
      evaluated. Moreover, French tissue banks are facing an accumulation of ungrafted
      samples. The aim of our work was to evaluate the implantation rate of
      cryopreserved parathyroid samples and the functionality of CPAT in a multicenter
      study. METHODS: Data from 9 French tissue banks were analyzed. CPAT functionality
      was defined as fully functional (normal parathyroid hormone [PTH] and calcium
      levels without treatment), partially functional (normal PTH levels but need for
      treatment to maintain normocalcemia), and nonfunctional (low PTH levels and need
      for treatment). For dialyzed patients, CPAT was considered nonfunctional if the
      PTH level in the nongrafted arm was less than 20 pg/mL, partially functional if
      the PTH level was between 20 and 50 pg/mL, and fully functional if the PTH level
      was between 50 and 300 pg/mL. RESULTS: The 9 centers had cryopreserved 1376
      samples of parathyroid tissue and only 22 (1.6%) had been autografted in 20
      patients (65% renal hyperparathyroidism, 20% multiple endocrine neoplasia type 1,
      15% "other") by 12 different surgical teams. The median duration of storage was
      11.1 months (range, 0.4-28.5). Only 2 autografts (10%) were fully functional, 2
      (10%) were partially functional, and 17 (80%) were nonfunctional at 26 months
      median follow-up. CONCLUSION: The reimplantation rate is low, and the
      functionality of CPAT is less than those published by experienced centers.
      Logistical and technical problems occurring in less experienced centers are
      probably the main reasons for nonfunctioning implants. Considering the results of
      this study, we suggest that cryopreservation of parathyroid glands should be
      abandoned when not performed in very large experimented centers, that CPAT should
      be used only for patients with hyperplasic parathyroid tissue, and that tissue
      samples should be systematically destroyed when patients do not have
      hypoparathyroidism or after 1 year of storage.

PMID- 20153008
TI  - Blood flow evaluation in high-frequency, 40 MHz imaging: a comparative study of
      four vector velocity estimation methods.
AB  - Ultrasonic imaging is often used to estimate blood flow velocity. Currently,
      estimates are carried out using Doppler-based techniques. However, there are a
      number of shortcomings such as the limited spatial resolution and the inability
      to estimate longitudinal flows. Thus, alternative methods have been proposed to
      overcome them. Difficulties are notably encountered with high-frequency imaging
      systems that use swept-scan techniques. In this article, we propose to compare
      four vector velocity estimation methods that are complementary to Doppler,
      focusing on 40 MHz, high-frequency imaging. The goal of this study is to evaluate
      which method could circumvent the limitations of Doppler methods for evaluation
      of microcirculation, in the vessels having diameter on the order of 1 mm. We used
      two region-based approaches, one decorrelation-based approach and one
      spatiotemporal approach. Each method has been applied to seven flow sequences
      with various orientations and mean velocities. Four sequences were simulated with
      a system approach based on a 3D set of moving scatterers. Three experimental
      sequences were carried out by injecting blood-mimicking fluid within a gelatin
      phantom and then acquiring images with Visualsonics, Vevo 660 system. From
      velocity estimates, several performance criteria such as the normalized mean
      error or the normalized mean standard deviation were defined to compare the
      performance of the four estimators. The results show that region-based methods
      are the most accurate exhibiting mean errors less than 10% and mean standard
      deviation less than 13%. However, region-based approaches are those that require
      the highest calculative cost compared to the decorrelation-based method, which is
      the fastest. Finally, the spatiotemporal approach appeared to be a trade-off in
      terms of computational complexity and accuracy of estimates. It provides
      estimates with errors less than 10% for mean velocity and the CPU time is
      approximately 17s for a ROI of size 40*80 pixels.

PMID- 20153009
TI  - Induction of antibody-mediated neutralization in SIVmac239 by a naturally
      acquired V3 mutation.
AB  - Achieving humoral immunity against human immunodeficiency virus (HIV) is a major
      obstacle in AIDS vaccine development. Despite eliciting robust humoral responses
      to HIV, exposed hosts rarely produce broadly neutralizing antibodies. The present
      study utilizes simian immunodeficiency virus (SIV) to identify viral epitopes
      that conferred antibody neutralization to clone SIV/17E-CL, an in vivo variant
      derived from neutralization resistant SIVmac239. Neutralization assays using
      rhesus macaque monoclonal antibodies were performed on viruses engineered to
      express single or multiple amino acid mutations. Results identified a single
      amino acid mutation, P334R, in the carboxy-terminal half of the V3 loop as a
      critical residue that induced neutralization while retaining normal glycoprotein
      expression on the surface of the virus. Furthermore, the R334 residue yielded
      neutralization sensitivity by antibodies recognizing diverse conformational and
      linear epitopes of gp120, suggesting that neutralization phenotype was a
      consequence of global structural changes of the envelope protein rather than a
      specific site epitope.

PMID- 20153010
TI  - Nuclear matrix protein SMAR1 represses HIV-1 LTR mediated transcription through
      chromatin remodeling.
AB  - Nuclear Matrix and MARs have been implicated in the transcriptional regulation of
      host as well as viral genes but their precise role in HIV-1 transcription remains
      unclear. Here, we show that >98% of HIV sequences contain consensus MAR element
      in their promoter. We show that SMAR1 binds to the LTR MAR and reinforces
      transcriptional silencing by tethering the LTR MAR to nuclear matrix. SMAR1
      associated HDAC1-mSin3 corepressor complex is dislodged from the LTR upon
      cellular activation by PMA/TNFalpha leading to an increase in the acetylation and
      a reduction in the trimethylation of histones, associated with the recruitment of
      RNA Polymerase II on the LTR. Overexpression of SMAR1 lead to reduction in LTR
      mediated transcription, both in a Tat dependent and independent manner, resulting
      in a decreased virion production. These results demonstrate the role of SMAR1 in
      regulating viral transcription by alternative compartmentalization of LTR between
      the nuclear matrix and chromatin.

PMID- 20153012
TI  - Cellular factors associated with latency and spontaneous Epstein-Barr virus
      reactivation in B-lymphoblastoid cell lines.
AB  - EBV-immortalized B-lymphoblastoid cell lines are used as models for cellular
      transformation and as antigen-presenting cells in immunological assays. LCLs vary
      in surface markers and other phenotypic properties, but it is not known how this
      heterogeneity relates to the EBV life cycle. To explore correlations, we examined
      62 LCLs for cellular and viral phenotypes. LCLs generated from pediatric and
      adult donors could similarly be categorized as either low in EBV copy number or
      fluctuating within a high range. High-copy status accompanied higher lytic viral
      gene expression and lower latent gene expression. Inhibiting lytic EBV
      replication did not affect cellular phenotype or lytic switch protein expression,
      indicating that an LCL's lytic permissivity was a stable property. Among the
      cellular genes overexpressed in permissive LCLs were unfolded protein response
      genes and plasma cell markers. Among genes overexpressed in non-permissive LCLs
      were transcription factors involved in maintaining B cell lineage, in particular
      EBF1. This study suggests previously undetected mechanisms by which cellular
      pathways influence the lytic reactivation of EBV.

PMID- 20153013
TI  - Rapid detection of Escherichia coli in water using a hand-held fluorescence
      detector.
AB  - The quantification of pathogenic bacteria in an environmental or clinical sample
      commonly involves laboratory-based techniques and results are not obtained for 24
      72 h after sampling. Enzymatic analysis of microbial activity in water and other
      environmental samples using fluorescent synthetic substrates are well-established
      and highly sensitive methods in addition to providing a measure of specificity
      towards indicative bacteria. The enzyme beta-d-glucuronidase (GUD) is a specific
      marker for Escherichia coli and 4-methylumbelliferone-beta-D-glucuronide (MUG) a
      sensitive substrate for determining the presence of E. coli in a sample. However,
      currently used procedures are laboratory-based and require bench-top fluorimeters
      for the measurement of fluorescence resulting from the enzyme-substrate reaction.
      Recent developments in electronic engineering have led to the miniaturisation of
      fluorescence detectors. We describe the use of a novel hand-held fluorimeter to
      directly analyse samples obtained from the River Thames for the presence of E.
      coli. The results obtained by the hand-held detector were compared with those
      obtained with an established fluorescent substrate assay and by quantifying
      microbial growth on a chromogenic medium. Both reference methods utilised
      filtration of water samples. The miniaturised fluorescence detector was used and
      incubation times reduced to 30 min making the detection system portable and
      rapid. The developed hand-held system reliably detected E. coli as low as 7
      cfu/mL river water sample. Our study demonstrates that new hand-held fluorescence
      measurement technology can be applied to the rapid and convenient detection of
      bacteria in environmental samples. This enables rapid monitoring to be carried
      out on-site. The technique described is generic and it may, therefore, be used in
      conjunction with different fluorescent substrates which allows the assessment of
      various target microorganisms in biological samples.

PMID- 20153011
TI  - Inhibition of LINE-1 and Alu retrotransposition by exosomes encapsidating
      APOBEC3G and APOBEC3F.
AB  - Human cytidine deaminases, including APOBEC3G (A3G) and A3F, are part of a
      cellular defense system against retroviruses and retroelements including non-LTR
      retrotransposons LINE-1 (L1) and Alu. Expression of cellular A3 proteins is
      sufficient for inhibition of L1 and Alu retrotransposition, but the effect of A3
      proteins transferred in exosomes on retroelement mobilization is unknown. Here,
      we demonstrate for the first time that exosomes secreted by CD4(+)H9 T cells and
      mature monocyte-derived dendritic cells encapsidate A3G and A3F and inhibit L1
      and Alu retrotransposition. A3G is the major contributor to the inhibitory
      activity of exosomes, however, the contribution of A3F in H9 exosomes cannot be
      excluded. Additionally, we show that exosomes encapsidate mRNAs coding for A3
      proteins. A3G mRNA, and less so A3F, was enriched in exosomes secreted by H9
      cells. Exosomal A3G mRNA was functional in vitro. Whether exosomes inhibit
      retrotransposons in vivo requires further investigation.

PMID- 20153014
TI  - Polychlorobiphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and
      dibenzofurans (PCDFs) in fruit and vegetables from an industrial area in northern
      Italy.
AB  - Polychlorobiphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and
      dibenzofurans (PCDFs) were measured in fruit and vegetables (n=113) harvested in
      different parts of the Mantua district, in northern Italy, and levels were used
      for assessing the exposure of the population to the contaminants through these
      food items. Concentrations in fruit and vegetables were in the range 33.39
      10130pgg(-1)fresh weight (fw) for the sum of the 26PCBs analyzed (Sigma(26PCBs)),
      14.86-4504pgg(-1)fw for the six "indicator" non-dioxin-like PCBs (Sigma(6 NDL
      PCBs)), and 0.0004-1.398pg toxic equivalent (TEQ)g(-1)fw for the dioxin-like PCBs
      (SigmaTEQ(DL-PCBs)). Altogether fruit and vegetables made only a limited
      contribution to total dietary PCB intake, as the estimated total mean daily
      intake (TMDI) of Sigma(26PCBs) through these food items was 10.1% in children and
      10.4% in adults of the minimal risk level (MRL) for PCBs, while the TMDI of
      SigmaTEQ(DL-PCBs) was 3.3% in children and 3.7% in adults of the tolerable daily
      intake (TDI) for dioxin-like compounds. The contribution of fruit and vegetables
      to total PCDD and PCDF dietary intake could not be assessed because
      concentrations of these congeners were almost all below the limit of detection in
      most of the crops analyzed. This study also found that PCB levels in rosemary
      were much higher than in any other crop, suggesting that rosemary leaves
      accumulate PCBs and that this plant might be proposed as a "sentinel" of the
      presence of these contaminants in the environment.

PMID- 20153015
TI  - Determination of PCDD/F, dioxin-like PCB and PAH levels in olive and olive oil
      samples from areas affected by the fires in summer 2007 in Greece.
AB  - During the summer of 2007, a series of massive forest fires broke out in several
      areas across Greece. The main sources of PCDD/Fs and dioxin-like PCBs in Greece
      are considered to be the uncontrolled combustion of municipal solid waste in open
      landfills and accidental fires in forest, rural and industrial areas. Combustion
      may also lead to the formation of PAHs, which are fat soluble substances of
      considerable toxicity. The objective of this study was to investigate PCDD/F,
      dioxin-like PCB and PAH contamination of olive oil produced in fire-affected
      areas. Olive oil is a very significant agricultural product of Greece. Samples
      for this study were collected from all affected oil producing areas after the
      fire and 1year later. PCDD/Fs, dioxin-like PCBs and PAHs were at normal levels in
      all samples analysed.

PMID- 20153016
TI  - Is primate-like quadrupedalism necessary for fine-branch locomotion? A test using
      sugar gliders (Petaurus breviceps).
AB  - Locomotor features shared by arboreal marsupials and primates are frequently
      cited as a functional complex that evolved in the context of a "fine branch
      niche." Adaptation to a fine branch niche cannot be understood without
      considering that small and large arboreal mammals may differ in their
      biomechanical response to a given branch size. We tested the effects of substrate
      diameter and orientation on quadrupedal kinematics in a small arboreal marsupial
      (the sugar glider, Petaurus breviceps). P. breviceps individuals were filmed
      moving across a flat horizontal surface and on horizontal, inclining and
      declining poles of diameter 2.5, 1.0, and 0.5cm. Gait frequencies, limb phases,
      speeds and duty factors were compared across substrate conditions. P. breviceps
      had a clear preference for lateral sequence/diagonal couplets gaits, regardless
      of substrate type, diameter or orientation. Limb phase was significantly
      influenced by substrate type (higher limb phases on poles vs. the flat surface)
      and by orientation (higher limb phases on inclined vs. horizontal poles), but was
      not influenced by pole diameter. Speed was lowest on declines, and duty factors
      (at a given speed) were highest on the flat board, smallest pole, and on
      declines. P. breviceps exhibited some parallels, but also some departures from
      the characteristic patterns of other arboreal marsupials and primates. Notably,
      limb phase values, on average, remained lower in P. breviceps than those recorded
      for primates or other arboreal marsupials. We suggest that arboreal mammals of
      different body sizes may use dissimilar, but apparently equally successful
      strategies for navigating a "fine branch niche."

PMID- 20153017
TI  - An isotopic investigation of mercury accumulation in terrestrial food webs
      adjacent to an Arctic seabird colony.
AB  - At Cape Vera (Devon Island, Nunavut, Canada), a seabird colony of northern
      fulmars (Fulmarus glacialis) congregates and releases nutrients through the
      deposition of guano to the coastal terrestrial environment, thus creating
      nutrient-fertilized habitats important to insects, birds, and mammals. Here we
      determined whether mercury was similarly enriched in various terrestrial food web
      components in this High Arctic coastal ecosystem due to seabird inputs. Stable
      isotopes (delta(15)N, delta(13)C) were used to identify trophic linkages and
      possible routes of contaminant transfer in the food web. Values of delta(15)N
      were significantly higher in lichens and certain plants collected closer to the
      bird colony, demonstrating a gradient of seabird influence, and were higher at
      Cape Vera than our reference site at Cape Herschel, on eastern Ellesmere Island,
      an area relatively unaffected by seabirds. In contrast, delta(13)C showed little
      variation among terrestrial species, suggesting minimal influence by seabirds.
      Concentrations of total mercury (THg) in primary producers and phyto/zooplankton
      were not significantly correlated with distance from the seabird colony or
      delta(15)N values, and were similar to other taxa from the High Arctic. Our
      results provide novel data on THg in several Arctic taxa where concentrations
      have not been reported previously. Moreover, the analyses indicate that
      delta(15)N is significantly enriched in the adjacent environment by guano
      fertilization, but our study was unable to show an enrichment of THg and
      delta(13)C in the terrestrial food web near the seabird colony.

PMID- 20153018
TI  - Pollution of montane soil with Cu, Zn, As, Sb, Pb, and nitrate in Kanto, Japan.
AB  - Soil cores and rainwater were sampled under canopies of Cryptomeria japonica in
      four montane areas along an atmospheric depositional gradient in Kanto, Japan.
      Soil cores (30cm in depth) were divided into 2-cm or 4-cm segments for analysis.
      Vertical distributions of elemental enrichment ratios in soils were calculated as
      follows: (X/Al)(i)/(X/Al)(BG) (where the numerator and denominator are
      concentration ratios of element-X and Al in the i- and bottom segments of soil
      cores, respectively). The upper 14-cm soil layer showed higher levels of Cu, Zn,
      As, Sb, and Pb than the lower (14-30cm) soil layer. In the four areas, the
      average enrichment ratios in the upper 6-cm soil layer were as follows: Pb
      (4.93)>or=Sb (4.06)>or=As (3.04)>Zn (1.71)>or=Cu (1.56). Exogenous elements
      (kg/ha) accumulated in the upper 14-cm soil layer were as follows: Zn (26.0)>Pb
      (12.4)>Cu (4.48)>or=As (3.43)>or=Sb (0.49). These rank orders were consistent
      with those of elements in anthropogenic aerosols and polluted (roadside) air,
      respectively, indicating that air pollutants probably caused enrichment of these
      elements in the soil surface layer. Approximately half of the total
      concentrations of As, Sb, and Pb in the upper 14-cm soil layer were derived from
      exogenous (anthropogenic) sources. Sb showed the highest enrichment factor in
      anthropogenic aerosols, and shows similar deposition behavior to NO(3)(-), which
      is a typical acidic air pollutant. There was a strong correlation between Sb and
      NO(3)(-) concentrations in rainfall (e.g., in the throughfall under C. japonica:
      [NO(3)(-)]=21.1 [dissolved Sb], r=0.938, p<0.0001, n=182). Using this
      correlation, total (cumulative) inputs of NO(3)(-) were estimated from the
      accumulated amounts of exogenous Sb in soils, i.e., 16.7t/ha at Mt. Kinsyo (most
      polluted), 8.6t/ha at Mt. Tsukuba (moderately polluted), and 5.8t/ha at the Taga
      mountain system (least polluted). There are no visible ecological effects of
      these accumulated elements in the Kanto region at present. However, the
      concentrations of some elements are within a harmful range, according to the
      Ecological Soil Screening Levels determined by the U.S. Environmental Protection
      Agency.

PMID- 20153019
TI  - Degradation models and ecotoxicity in marine waters of two antifouling compounds:
      sodium hypochlorite and an alkylamine surfactant.
AB  - Industrial wastes have a substantial impact on coastal environments. Therefore,
      to evaluate the impact of cooling water discharges from coastal power plants, we
      studied the kinetics of the degradative processes and the ecotoxicity of two
      antifouling products: (1) a classic antifouling product; sodium hypochlorite
      (NaClO) and (2) an alternative one; aliphatic amines (commercial under the
      registered trade mark Mexel432). To assess the persistence of both compounds the
      decay of sodium hypochlorite and the primary biodegradation rate of Mexel432 were
      determined in natural seawater at 20 degrees C. The results indicated a more
      rapid decay of NaClO than Mexel432. The degradation behavior of both chemicals
      was described following a logistic model, which permitted calculating kinetic
      parameters such as t(50) or t(90). The t(50) was 1h and 2d for NaClO and
      Mexel432, respectively. To evaluate the potential risks of the aforementioned
      treatments to marine organisms, the acute toxicity of both antifouling products
      was studied on the microalgae Isochrysis galbana and Dunaliella salina, and on
      the invertebrate Brachionus plicatilis, using growth inhibition and death tests
      as toxic response, respectively. For I. galbana, the 96-h EC(50) values were
      2.91+/-0.15mg/L of NaClO and 4.55+/-0.11mg/L of Mexel432. D. salina showed values
      of 96-h EC(50) of 1.73+/-0.16mg/L of NaClO and 7.21+/-0.1mg/L of Mexel432.
      Brachionus plicatilis showed a 24-h LC(50) of 1.23+/-0.1mg/L of NaClO and 3.62+/
      0.37mg/L of Mexel432. Acute toxicity was highly dependent on the chemical and
      species tested. NaClO presented more toxic effects than Mexel432, also B.
      plicatilis was the most sensitive species in both cases. The lowest NOECs
      obtained, 0.25mg/L for NaClO and 2.12mg/L for Mexel432, were similar to the
      theoretical residual concentrations of these biocides in cooling water
      discharges. Therefore, these discharges can cause undesirable negative effects
      upon the aquatic organisms present.

PMID- 20153022
TI  - Factor VIIa and tissue factor--from cell biology to animal models.
AB  - Binding of factor VIIa (FVIIa) to tissue factor (TF) and the subsequent
      initiation of the clotting cascade is essential for hemostasis. However, the
      aberrant expression of FVIIa-TF contributes to thrombosis. Despite the tremendous
      progress made in the past 25years in understanding the molecular mechanisms
      involved in the interaction between FVIIa and TF, there is less known about the
      cell biology of these proteins. Availability of hemophilic mice (by specific
      knock-out of FVIII or FIX genes) and novel TF transgenic mice has allowed us in
      recent years to investigate the importance of TF-FVIIa-induced coagulation from
      wound healing to sepsis. This supplement explores new aspects of TF-FVIIa
      biology, with a particular focus on structural biology, cell biology and animal
      models.

PMID- 20153023
TI  - Future pharmacological strategies in management of Haemophilia.

PMID- 20153024
TI  - The interaction of recombinant factor VIIa with platelet glycoprotein Ib.
AB  - Recombinant factor VIIa (rFVIIa) exerts potent prohemostatic activities via both
      tissue factor-dependent and -independent mechanisms. Tissue factor-independent
      enhancement of hemostasis involves a direct interaction of rFVIIa with the
      activated platelet membrane resulting in factor X activation. We have recently
      shown that rFVIIa binds to the platelet glycoprotein Ib/IX/V complex in addition
      to the negatively charged membrane surface. This interaction appears to slightly
      enhance tissue factor-independent thrombin generation. These findings add to our
      understanding of the mechanism of action of rFVIIa and may lead to improved
      therapeutic use of the drug.

PMID- 20153025
TI  - Influence of anticoagulant therapy with vitamin K antagonists on plasma levels of
      coagulation factor VIII.
AB  - Vitamin K-antagonists (VKA) decreases vitamin K coagulation factors. To
      counterbalance this effect, it has been postulated that non-vitamin K proteins
      increase during VKA treatment. To investigate if VKA affect FVIII, a cohort of
      1772 patients referred from Jan 1997 to Oct 2008 to our Thrombosis Center for a
      thrombophilia screening after at least 3 months from diagnosis of first venous
      thrombosis was studied. At the time of blood sampling, 1303 patients had
      discontinued VKA for at least one month, whereas the remaining 469 were still
      taking VKA. FVIII was significantly higher in patients on VKA than in those who
      had discontinued VKA (mean+/-SD: 144+/-41 IU/dL and 134+/-40 IU/dL, respectively,
      p<0.0001), also after adjustment for sex, age, body mass index, thrombophilia and
      time elapsed from thrombosis in a multiple linear regression analysis. In order
      to avoid overestimation of FVIII levels, patients should be preferentially tested
      after VKA discontinuation.

PMID- 20153026
TI  - Effects of eccentric and concentric training on capillarization and myosin heavy
      chain contents in rat skeletal muscles after hindlimb suspension.
AB  - We studied the effects of different protocols of post-disuse rehabilitation on
      angiogenesis and myosin heavy chain (MHC) content in rat hindlimb muscles after
      caudal suspension. Thirty female Wistar rats were divided into five groups: (1)
      Control I, (2) Control II, (3) Suspended, (4) Suspended trained on declined
      treadmill, and (5) Suspended trained on flat treadmill. Fragments of the soleus
      and tibialis anterior (TA) muscles were frozen and processed by electrophoresis
      and immunohistochemistry (CD31 antibody). Hindlimb suspension caused reduction of
      capillary/fiber (C/F) ratios and contents of MHC type I (MHCI) in the soleus in
      parallel to increased capillary density. Flat treadmill protocols increased the
      content of the MHCI isoform. The C/F ratio was increased by concentric training
      after hypokinesis, but was not modified by eccentric training, which caused a
      greater reduction of capillary density compared to the other protocols. In the TA
      muscle, hindlimb suspension caused a non-significant increase in capillary
      density and C/F ratio with limited changes in MHC. The present data demonstrate
      that the different training protocols adopted and the functional performance of
      the muscles analyzed caused specific changes in capillarization and in the
      content of the various MHC types.

PMID- 20153027
TI  - Surveillance for the detection of recurrent ovarian cancer: survival impact or
      lead-time bias?
AB  - OBJECTIVE: To compare the survival impact of diagnosing recurrent disease by
      routine surveillance testing versus clinical symptomatology in patients with
      recurrent epithelial ovarian cancer (EOC) who have achieved a complete response
      following primary therapy. METHODS: We identified all patients who underwent
      primary surgery for EOC at two institutions between 1/1997 and 12/2004 and were
      diagnosed with recurrent disease following a complete clinical response to
      primary chemotherapy. Survival and post-recurrence management were compared
      between asymptomatic patients in which recurrent disease was diagnosed at a
      scheduled visit by routine surveillance testing and symptomatic patients in which
      recurrent disease was diagnosed based on clinical symptomatology at an
      unscheduled office visit or hospitalization. RESULTS: Of the 121 patients that
      met inclusion criteria, 22 (18.2%) were diagnosed with a symptomatic recurrence.
      Median primary PFS was similar for asymptomatic and symptomatic patients (24.8
      versus 22.6 months, P = 0.36); however, post-recurrence survival was
      significantly greater in asymptomatic patients (45.0 versus 29.4 months, P =
      0.006). Secondary cytoreductive surgery (SCRS) was attempted equally in both
      groups (41% versus 32%, P = NS); however, optimal residual disease (<or=5mm) was
      more often achieved in asymptomatic patients (90% versus 57%, P = 0.053). On
      multivariate analysis, detection of asymptomatic recurrence was a significant and
      independent predictor of improved overall survival (P = 0.001). Median OS was
      significantly greater for asymptomatic patients (71.9 versus 50.7 months, P =
      0.004). CONCLUSIONS: In patients with platinum-sensitive EOC, detection of
      asymptomatic recurrences by routine surveillance testing was associated with a
      high likelihood of optimal SCRS in operative candidates and extended overall
      survival.

PMID- 20153028
TI  - Comparison between robot-assisted laparoscopic radical hysterectomy (RRH) and
      abdominal radical hysterectomy (ARH): a case control study from EIO/Milan.

PMID- 20153029
TI  - Overall asthma control: the relationship between current control and future risk.
AB  - BACKGROUND: Asthma guidelines emphasize both maintaining current control and
      reducing future risk, but the relationship between these 2 targets is not well
      understood. OBJECTIVE: This retrospective analysis of 5 budesonide/formoterol
      maintenance and reliever therapy (Symbicort SMART Turbuhaler(*)) studies assessed
      the relationship between asthma control questionnaire (ACQ-5) and Global
      Initiative for Asthma-defined clinical asthma control and future risk of
      instability and exacerbations. METHODS: The percentage of patients with Global
      Initiative for Asthma-defined controlled asthma over time was assessed for
      budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance
      therapies; higher dose inhaled corticosteroid (ICS), same dose ICS/long-acting
      beta(2)-agonist (LABA), and higher dose ICS/LABA plus short-acting beta(2)
      agonist. The relationship between baseline ACQ-5 and exacerbations was
      investigated. A Markov analysis examined the transitional probability of change
      in control status throughout the studies. RESULTS: The percentage of patients
      achieving asthma control increased with time, irrespective of treatment; the
      percentage Controlled/Partly Controlled at study end was at least similar to
      budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance
      therapies: higher dose ICS (56% vs 45%), same dose ICS/LABA (56% vs 53%), and
      higher dose ICS/LABA (54% vs 54%). Baseline ACQ-5 score correlated positively
      with exacerbation rates. A Controlled or Partly Controlled week predicted at
      least Partly Controlled asthma the following week (>or=80% probability). The
      better the control, the lower the risk of an Uncontrolled week. The probability
      of an exacerbation was related to current state and was lower with
      budesonide/formoterol maintenance and reliever therapy. CONCLUSIONS: Current
      control predicts future risk of instability and exacerbations.
      Budesonide/formoterol maintenance and reliever therapy reduces exacerbations
      versus comparators and achieves at least similar control.

PMID- 20153030
TI  - Sublingual immunotherapy in patients with allergic rhinoconjunctivitis caused by
      ragweed pollen.
AB  - BACKGROUND: Specific allergen immunotherapy is most often delivered
      subcutaneously, but sublingual immunotherapy may confer greater benefit in terms
      of tolerability and safety, accessibility, and improved antigen delivery.
      OBJECTIVE: This randomized, double-blind, placebo-controlled trial was conducted
      to identify a safe and effective maintenance dose range of sublingual
      standardized glycerinated short ragweed pollen extract in adults with ragweed
      induced rhinoconjunctivitis. METHODS: In May 2006, a total of 115 patients with
      ragweed-induced rhinoconjunctivitis were randomly allocated to placebo (n = 40),
      medium-dose extract (4.8 microg Amb a 1/d; n = 39), or high-dose extract (48
      microg Amb a 1/d; n = 36). In a 1-day (rush) dose-escalation regimen, ragweed
      pollen extract was administered sublingually in incremental doses until maximum
      tolerable or scheduled dose was reached and then maintained during the ragweed
      pollen season. Patient diaries were used to monitor nasal and ocular symptoms and
      medication. The primary endpoint was symptom score. RESULTS: Both active
      treatment groups achieved a 15% reduction in total rhinoconjunctivitis symptom
      scores compared with placebo during the entire ragweed pollen season, but the
      difference was not statistically significant (P > .10) However, in an analysis of
      covariance correcting for preseasonal symptoms, both mean daily symptom scores
      (0.19 +/- 1.16 vs 1.00 +/- 2.30) and medication scores (0.0003 +/- 1.64 vs 0.63
      +/- 1.06) for the entire pollen season were significantly reduced in the high
      dose versus placebo groups, respectively (P <or= .05). Ragweed-specific IgG,
      IgG(4), and IgA antibodies were increased after treatment in the medium- and high
      dose groups and not the placebo group. Frequency of adverse events was similar
      between the placebo and treatment groups, but oral-mucosal adverse events
      occurred more often with treatment. CONCLUSION: Standardized glycerinated short
      ragweed pollen extract administered sublingually at maintenance doses of 4.8 to
      48 microg Amb a 1/d was safe and can induce favorable clinical and immunologic
      changes in ragweed-sensitive subjects. However, additional trials are needed to
      establish efficacy.

PMID- 20153031
TI  - Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and
      airway inflammation in a murine model of asthma.
AB  - BACKGROUND: Disturbance in the delicate balance between L-arginine-metabolizing
      enzymes such as nitric oxide synthase (NOS) and arginase may lead to decreased L
      arginine availability to constitutive forms of NOS (endothelial NOS), thereby
      increasing the nitro-oxidative stress and airway hyperresponsiveness (AHR).
      OBJECTIVE: In this study, we investigated the effects of high doses of L-arginine
      on L-arginine-metabolizing enzymes and subsequent biological effects such as
      cyclic guanosine monophosphate production, lipid peroxidation, peroxynitrite,
      AHR, and airway inflammation in a murine model of asthma. METHODS: Different
      doses of L-arginine were administered to ovalbumin-sensitized and challenged
      mice. Exhaled nitric oxide, AHR, airway inflammation, T(H)2 cytokines, goblet
      cell metaplasia, nitro-oxidative stress, and expressions of arginase 1,
      endothelial NOS, and inducible NOS in lung were determined. RESULTS: L-arginine
      significantly reduced AHR and airway inflammation including bronchoalveolar
      lavage fluid eosinophilia, T(H)2 cytokines, TGF-beta1, goblet cell metaplasia,
      and subepithelial fibrosis. Further, L-arginine increased ENO levels and cyclic
      guanosine monophosphate in lung and reduced the markers of nitro-oxidative stress
      such as nitrotyrosine, 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine. This was
      associated with reduced activity and expression of arginase 1, increased
      expression of endothelial NOS, and reduction of inducible NOS in bronchial
      epithelia. CONCLUSION: We conclude that L-arginine administration may improve
      disordered nitric oxide metabolism associated with allergic airway inflammation,
      and alleviates some features of asthma.

PMID- 20153033
TI  - Trichuris suis might be effective in treating allergic rhinitis.

PMID- 20153032
TI  - Social stress and asthma: the role of corticosteroid insensitivity.
AB  - Psychosocial stress alters susceptibility to infectious and systemic illnesses
      and may enhance airway inflammation in asthma by modulating immune cell function
      through neural and hormonal pathways. Stress activates the hypothalamic-pituitary
      adrenal axis. Release of endogenous glucocorticoids, as a consequence, may play a
      prominent role in altering the airway immune homeostasis. Despite substantial
      corticosteroid and catecholamine plasma levels, chronic psychosocial stress
      evokes asthma exacerbations. Animal studies suggest that social stress induces
      corticosteroid insensitivity that in part may be a result of impaired
      glucocorticoid receptor expression and/or function. Such mechanisms likely
      promote and amplify airway inflammation in response to infections, allergen, or
      irritant exposure. This review discusses evidence of an altered corticosteroid
      responsive state as a consequence of chronic psychosocial stress. Elucidation of
      the mechanisms of stress-induced impairment of glucocorticoid responsiveness and
      immune homeostasis may identify novel therapeutic targets that could improve
      asthma management.

PMID- 20153034
TI  - Looking into the future of Trichuris suis therapy.

PMID- 20153036
TI  - Induction of anergic allergen-specific suppressor T cells using tolerogenic
      dendritic cells derived from children with allergies to house dust mites.
AB  - BACKGROUND: Dendritic cells (DCs) regulate the immune response to allergens in
      the lung; they induce either effector or regulatory T cells, which promote or
      suppress, respectively, the development of allergy. IL-10 is a potent
      immunosuppressive cytokine that induces type 1 regulatory (Tr1) T cells.
      OBJECTIVE: To generate allergen-specific Tr1 cells in vitro from children with
      allergy. METHODS: Monocyte-derived DCs from children with allergy to house dust
      mites (HDM) were generated by incubating the cells with IL-10 and pulsing them
      with Der p 2, a major HDM allergen, or by pulsing them with Der p 2 and
      incubating them with IL-10 during their last 2 days of differentiation. RESULTS:
      Der p 2-specific T-cell proliferation and T(H)2 cytokine production were
      significantly reduced when T cells from patients with allergy to HDM were
      activated with autologous Der p 2-pulsed DCs that had been differentiated or
      incubated with IL-10. T-cell lines generated with Der p 2-pulsed DCs that were
      differentiated with IL-10 were hyporesponsive to reactivation with Der p 2 and
      able to suppress Der p 2-specific T(H)2 effector cells. CONCLUSION: Dendritic
      cells differentiated in the presence of IL-10 and pulsed with allergen gave rise
      to a population of tolerogenic DCs that induced allergen-specific Tr1 cells. This
      finding represents an important step forward to the prospective clinical
      application of tolerogenic DCs to modulate allergen-specific T-cell responses.

PMID- 20153037
TI  - Endothelium-derived prostaglandin I(2) controls the migration of eosinophils.
AB  - BACKGROUND: Enhanced eosinophil migration from the blood into the tissue is a
      hallmark of allergic diseases. Prostaglandin (PG) I(2) is the major prostanoid
      released by endothelial cells. Mice deficient in PGI(2) receptors (IPs) show
      exaggerated eosinophilic inflammation in response to allergen. OBJECTIVE: We set
      out to determine the role of PGI(2) in eosinophil trafficking. METHODS: Human
      lung microvascular endothelial cells and purified human eosinophils were used to
      study adhesion and transendothelial migration. Morphologic studies were performed
      with fluorescence microscopy. RESULTS: PGI(2) markedly attenuated the migration
      of eosinophils through cell-free filters but had no effect on neutrophil
      migration. The inhibitory effect of PGI(2) on eosinophils was prevented by the IP
      antagonist Cay10441 and the adenylyl cyclase inhibitor SQ22536. Similarly, PGI(2)
      prevented the adhesion of eosinophils to fibronectin and the rapid upregulation
      and activation of the adhesion molecule CD11b. IP expression on eosinophils was
      confirmed by means of flow cytometry and Western blotting. Furthermore, when
      endothelial cells were treated with the COX inhibitor diclofenac to abolish
      PGI(2) production, adhesion of eosinophils to endothelial monolayers and
      subsequent transendothelial migration were markedly enhanced. Similarly, the IP
      antagonist enhanced eosinophil adhesion to endothelial cells. Inhibition of
      PGI(2) biosynthesis decreased the electrical resistance of endothelial monolayers
      and compromised the texture of adherent junctions, as visualized by means of VE
      cadherin and F-actin staining. CONCLUSION: We propose that endothelium-derived
      PGI(2) might be fundamental for the maintenance of the endothelial barrier
      function against infiltrating cells. These results suggest that selective IP
      agonists might have beneficial effects in allergic inflammation.

PMID- 20153038
TI  - Increased IL-33 expression by epithelial cells in bronchial asthma.

PMID- 20153041
TI  - An elastomeric patch derived from poly(glycerol sebacate) for delivery of
      embryonic stem cells to the heart.
AB  - We hypothesize that a combinatorial approach of ventricle constraint and stem
      cell therapy would offer a greater benefit for the treatment of heart failure
      than either strategy alone. A heart patch would serve two therapeutic purposes:
      biomechanical support and cell delivery. In this study, we describe a hybrid
      heart patch engineered from a synthetic elastomer, poly(glycerol sebacate) (PGS),
      supplemented with cardiomyocytes differentiated from human embryonic stem cells
      (hESCs). In line with two therapeutically relevant considerations, i.e.
      biocompatibility and cell delivery efficiency, the PGS was (a) pre-conditioned in
      culture medium for 6 days, and (b) prepared without gelatin coatings to
      facilitate detachment and delivery of cardiomyocytes following patch
      implantation. Following pre-conditioning under physiological conditions, the PGS
      patch material without gelatin coating was found to satisfactorily support
      cardiomyocyte viability and attachment, with active cell beating for periods of
      longer than 3 months until interrupted. Dynamic culture studies revealed that
      cells detached more efficiently from the uncoated surface of PGS than from
      gelatin-coated PGS. No significant differences were detected between the beating
      rates of human embryonic stem cell-derived cardiomyocytes on tissue culture plate
      and the pre-conditioned and gelatin-uncoated PGS. PGS patches sutured over the
      left ventricle of rats in vivo remained intact over a 2 week period without any
      deleterious effects on ventricular function. We conclude that PGS is a suitable
      biomaterial for stem cell-based regeneration strategies to restore cardiomyocyte
      function, and the hybrid heart patch engineered under optimal conditions would be
      a promising support device for the cardiac repair.

PMID- 20153039
TI  - Interferon alfa-2a versus combination therapy with interferon alfa-2a,
      interleukin-2, and fluorouracil in patients with untreated metastatic renal cell
      carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial.
AB  - BACKGROUND: In metastatic renal cell carcinoma combinations of interferon alfa
      2a, interleukin-2, and fluorouracil produce higher response rates and longer
      progression-free survival than do single agents. We aimed to compare overall
      survival in patients receiving combination treatment or interferon alfa-2a.
      METHODS: RE04/30012 was an open-label randomised trial undertaken in 50 centres
      across eight countries. 1006 treatment-naive patients diagnosed with advanced
      metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation
      to receive interferon alfa-2a alone or combination therapy with interferon alfa
      2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary
      endpoint was overall survival. Treatment groups were compared with a non
      stratified log-rank test. Analysis was by intention to treat. This study is
      registered, number ISRCTN 46518965. FINDINGS: 502 patients were randomly assigned
      to receive interferon alfa-2a and 504 to receive combined treatment. Median
      follow-up was 37.2 months (24.8-52.3). Median overall survival was 18.8 months
      (17.0-23.2) for patients receiving interferon alfa-2a versus 18.6 months (16.5
      20.6) for those receiving combination therapy. Overall survival did not differ
      between the two groups (hazard ratio 1.05 [95% CI 0.90-1.21], p=0.55; absolute
      difference 0.3% (-5.1 to 5.6) at 1 year and 2.7% (-8.2 to 2.9) at 3 years).
      Serious adverse events were reported in 113 (23%) patients receiving interferon
      alfa-2a and 131 (26%) of those receiving combined treatment. INTERPRETATION:
      Although combination therapy does not improve overall or progression-free
      survival compared with interferon alfa-2a alone, immunotherapy might still have a
      role because it can produce remissions that are of clinically relevant length in
      some patients. Identification of patients who will benefit from immunotherapy is
      crucial. FUNDING: UK Medical Research Council.

PMID- 20153042
TI  - Multiscale osteointegration as a new paradigm for the design of calcium phosphate
      scaffolds for bone regeneration.
AB  - The role of macropore size (>100 microm) and geometry in synthetic scaffolds for
      bone regeneration has been studied extensively, but successful translation to the
      clinic has been slow. Significantly less attention has been given to porosity at
      the microscale (0.5-10 microm). While some have shown that microporosity in
      calcium phosphate (CaP)-based scaffolds can improve rate and extent of bone
      formation in macropores, none has explored microporosity as an additional and
      important space for bone ingrowth. Here we show osteointegration of biphasic
      calcium phosphate (BCP) scaffolds at both the macro and micro length scales.
      Bone, osteoid, and osteogenic cells fill micropores in scaffold rods and
      osteocytes are embedded in mineralized matrix in micropores, without the addition
      of growth factors. This work further highlights the importance of considering
      design parameters at the microscale and demonstrates the possibility for a bone
      scaffold composite with no "dead space." Embedded osteocytes distributed
      throughout microporous rods may form a mechanosensory network, which would not be
      possible in scaffolds without microporosity. Multiscale osteointegration has the
      potential to greatly improve overall performance of these scaffolds through an
      improvement of mechanical properties, load transfer, and stability in the long
      and short term, and represents a new paradigm for scaffold design.

PMID- 20153043
TI  - Chondrogenic differentiation of human adipose-derived stem cells in polyglycolic
      acid mesh scaffolds under dynamic culture conditions.
AB  - Chondrogenic differentiation of human adult adipose-derived stem cells was
      studied in vitro for the development of engineered cartilage tissue. Cells
      cultured under dynamic conditions in polyglycolic acid (PGA) scaffolds produced
      substantially higher glycosaminoglycan (GAG) and total collagen levels than cells
      in pellet cultures. This result reflects the importance of cell attachment and
      cell-scaffold interactions in stem cell differentiation and chondrogenesis.
      Although gene expression levels for both aggrecan and collagen type II were up
      regulated significantly in PGA cultures treated with transforming growth factor
      beta1 (TGF-beta1), synthesis of GAG but not collagen type II was enhanced in
      tissue constructs when TGF-beta1 was added to the medium. Bone morphogenetic
      protein-6 (BMP-6) in the presence of TGF-beta1 was effective in improving GAG and
      total collagen production when the cells were pre-treated with fibroblast growth
      factor-2 (FGF-2) prior to scaffold seeding. Extending the culture duration from 2
      to 5 weeks did not improve cartilage development in PGA scaffolds; loss of cells
      from the constructs suggested that the rate of scaffold degradation exceeded the
      rate of replacement by ECM during the 5-week period. Stem cells in PGA scaffolds
      were cultured in perfusion-type recirculation bioreactors operated with periodic
      medium flow reversal. The highest levels of GAG and collagen type II accumulation
      were achieved in the bioreactor cultures after the seeding cell density was
      increased from 2x10(7) to 4x10(7) cells per scaffold.

PMID- 20153044
TI  - The ability of corneal epithelial cells to recognize high aspect ratio
      nanostructures.
AB  - The basement membrane of the human corneal epithelium comprises topographic
      features including fibers, pores, and elevations with feature dimensions on the
      order of 20-400 nm. Understanding the impact of sub-micron and nanotopography on
      corneal cell behavior will contribute to our understanding of biomechanical cues
      and will assist in the design of improved synthetic corneal implants. We utilized
      well defined ridge and groove wave-like nanostructures (wave ordered structures,
      WOS) of 60-140 pitches (30-70 nm ridge widths) and 200 nm depths to assess human
      corneal epithelial cell (HCEC) contact guidance and to establish HCEC contact
      acuity defined as the lower limit in feature dimensions at which cells respond to
      biomimetic topographic cues. Results using the WOS substrates demonstrate that
      HCEC contact acuity is in the range of 60 nm pitch for cells in a serum-free
      basal medium (EpiLife) and in the range of 90 nm pitch for cells in epithelial
      medium. To further investigate the influence of HCEC contact acuity in the
      presence of larger topographic cues, we fabricated 70 nm pitch WOS-overlaid
      parallel to the top of the ridges of 800-4000 nm pitch. HCEC cultured in
      epithelial medium demonstrate a significant increase in the percent of cells
      aligning to 4000 nm pitch topography with WOS-overlay compared to controls (both
      flat and 70 nm WOS alone) and 4000 nm pitch topography alone. These results
      highlight the significance of the lower range of basement membrane scale
      topographic cues on cell response and allow for improved prosthetic design.

PMID- 20153045
TI  - Heparin-based hydrogel as a matrix for encapsulation and cultivation of primary
      hepatocytes.
AB  - Primary hepatocytes are commonly used as liver surrogates in toxicology and
      tissue engineering fields, therefore, maintenance of functional hepatocytes in
      vitro is an important topic of investigation. This paper sought to characterize
      heparin-based hydrogel as a three-dimensional scaffold for hepatocyte culture.
      The primary rat hepatocytes were mixed with a prepolymer solution comprised of
      thiolated heparin and acrylated poly(ethylene glycol) (PEG). Raising the
      temperature from 25 degrees to 37 degrees C initiated Michael addition reaction
      between the thiol and acrylated moieties and resulted in formation of hydrogel
      with entrapped cells. Analysis of liver-specific products, albumin and urea,
      revealed that the heparin hydrogel was non-cytotoxic to cells and, in fact,
      promoted hepatic function. Hepatocytes entrapped in the heparin-based hydrogel
      maintained high levels of albumin and urea synthesis after three weeks in
      culture. Because heparin is known to bind growth factors, we incorporated
      hepatocyte growth factor (HGF)-an important liver signaling molecule - into the
      hydrogel. HGF release from heparin hydrogel matrix was analyzed using enzyme
      linked immunoassay (ELISA) and was shown to occur in a controlled manner with
      only 40% of GF molecules released after 30 days in culture. Importantly,
      hepatocytes cultured within HGF-containing hydrogels exhibited significantly
      higher levels of albumin and urea synthesis compared to cells cultured in the
      hydrogel alone. Overall, heparin-based hydrogel showed to be a promising matrix
      for encapsulation and maintenance of difficult-to-culture primary hepatocytes. In
      the future, we envision employing heparin-based hyrogels as matrices for in vitro
      differentiation of hepatocytes or stem cells and as vehicles for transplantation
      of these cells.

PMID- 20153047
TI  - Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone
      regeneration in a critical size defect of the sheep tibia and the influence of
      platelet-rich plasma.
AB  - Aim of the present study was to compare the osteogenic potential of bone marrow
      derived mesenchymal stem cells (BMSC) and adipose-tissue derived stem cells (ASC)
      and to evaluate the influence of platelet-rich plasma (PRP) on the osteogenic
      capacity of ASC in a large animal model. Ovine BMSC (BMSC-group) and ASC (ASC
      group) were seeded on mineralized collagen sponges and implanted into a critical
      size defect of the sheep tibia (n=5 each). In an additional group, platelet-rich
      plasma (PRP) was used in combination with ASC (PRP-group). Unloaded mineralized
      collagen (EMPTY-group) served as control (n=5 each). Radiographic evaluation was
      performed every 2 weeks, after 26 weeks histological analysis was performed.
      Radiographic evaluation revealed a significantly higher amount of newly formed
      bone in the BMSC-group compared to the ASC-group at week 10 and compared to EMPTY
      group from week 12 (all p<0.05). A superiority on radiographic level concerning
      bone formation of the PRP-group versus the empty control group was found
      (p<0.05), but not for the ASC-group. Histological analysis confirmed radiographic
      evaluation finding analogous significances. In conclusion, ASC seem to be
      inferior to BMSC in terms of their osteogenic potential but that can partially be
      compensated by the addition of PRP.

PMID- 20153046
TI  - The effect of immobilization of thrombin inhibitors onto self-assembled
      monolayers on the adsorption and activity of thrombin.
AB  - Thrombus formation is the major problem associated with biomaterials for blood
      contact medical devices. The immobilization of inhibitors to thrombin, a serine
      protease that plays a central role on the coagulation system, on the surface of
      biomaterials should be a good strategy to avoid blood clotting and increase their
      hemocompatibility. The aim of this work is the design of a nanostructured surface
      with capacity to adsorb and inactivate thrombin. The pentapeptide sequence d
      Phenylalanine-Proline-Arginine-Proline-Glycine (fPRPG), that was described as a
      thrombin inhibitor, was immobilized onto tetra(ethylene glycol) terminated self
      assembled monolayers (EG4-SAMs). Surface containing different amounts of fPRPG
      were prepared using different concentrations of N,N'-Carbonyldiimidazole (CDI)
      during immobilization. The efficiency of fPRPG immobilization was followed using
      ellipsometry, contact angle measurements, Infrared reflection absorption
      spectroscopy (IRRAS) and X-ray photoelectron spectroscopy (XPS). Thrombin
      adsorption was quantified using radiolabelled thrombin and its activity in
      solution and after adsorption on the developed surfaces was assessed using a
      chromogenic assay. It was found that, although the immobilization of fPRPG on to
      EG4-SAMs does not increase its selectivity to thrombin, the activity of the
      adsorbed thrombin was inhibited in a peptide concentration dependent way. We
      concluded that SAMs with fPRPG immobilized in high amounts can be used as
      thrombin-inhibitor surfaces, which is a good step on the development of new
      surfaces for blood contact devices.

PMID- 20153048
TI  - Surface structural conformations of fibrinogen polypeptides for improved
      biocompatibility.
AB  - This work reports on how incorporation of silica nanocages into poly(urethane)
      copolymers (PU) affects conformational orientations of adsorbed fibrinogen and
      how different surfaces subsequently influenced HeLa cell attachment and
      proliferation. Incorporation of 2 wt% silica nanocages into poly(urethane) (PU4)
      substantially altered the surface topography of the films and some 50% of the
      surface was covered with the nanocages due to their preferential exposure. AFM
      studies revealed the deposition of a dense protein network on the soft polymeric
      domains of PU4 and much reduced fibrinogen adsorption on the hard nanocage
      domains. As on the bare SiO(2) control surface, fibrinogen molecules adsorbed on
      top of the hard nanocages mainly took the dominant trinodular structures in
      monomeric and dimeric forms. In addition, net positively charged long alpha
      chains were prone to being hidden beneath the D domains whilst gamma chains
      predominantly remained exposed. Dynamic interfacial adsorption as probed by
      spectroscopic ellipsometry revealed fast changes in interfacial conformation
      induced by electrostatic interactions between different segments of fibrinogen
      and the surface, consistent with the AFM imaging. On the PU surfaces without
      nanocage incorporation (PUA), however, adsorbed fibrinogen molecules formed beads
      like chain networks, consistent with the structure featured on the soft PU4
      domains, showing very different effects of surface chemical nature. Monoclonal
      antibodies specific to the alpha and gamma chains showed reduced alpha but
      increased gamma chain binding at the silicon oxide control and PU4 surfaces,
      whilst on the PUA, C18 and amine surfaces (organic surface controls) the opposite
      binding trend was detected with alpha chain binding dominant, showing different
      fibrinogen conformations. Cell attachment studies revealed differences in cell
      attachment and proliferation, consistent with the different polypeptide
      conformations on the two types of surfaces, showing a strong preference to the
      extent of exposure of gamma chains.

PMID- 20153049
TI  - Establishment and characterization of a novel canine B-cell line derived from a
      spontaneously occurring diffuse large cell lymphoma.
AB  - Cell lines derived from spontaneous tumors serve as a research tool for cancer
      cell biology and new anti-cancer drug development. Isolation and propagation of
      canine lymphoma cell lines is difficult, thus only a few are available. Now we
      have established a new B-cell lymphoma cell line CLBL-1 from a dog with confirmed
      stage IV diffuse large cell lymphoma. Immunophenotyping of these CLBL-1 cells
      showed positive staining for CD11a, CD79alphacy, CD45, CD45RA, MHC II and cells
      were negative for CD3, CD4, CD5, CD8, CD11d, CD14, CD21, CD34, CD56 and T-cell
      receptor-gammadelta (TCR-gammadelta). PCR analysis for TCR-gamma and
      immunoglobulin heavy chain (IgH) gene rearrangements yielded a monoclonal result
      for the IgH gene. Furthermore, the clonality of IgH gene rearrangement was
      confirmed by sequencing of 16 positive bacterial clones. As canine lymphoma
      resembles non-Hodgkin's lymphoma (NHL) in humans in many respects, this new cell
      line, will promote translational and comparative lymphoma research in humans and
      dogs.

PMID- 20153050
TI  - Case of erythrophagocytosis in a patient with mantle cell lymphoma and cold
      agglutinin disease.

PMID- 20153051
TI  - The prevalence of childhood adversity among healthcare workers and its
      relationship to adult life events, distress and impairment.
AB  - OBJECTIVE: We investigated the prevalence of childhood adversity among healthcare
      workers and if such experiences affect responses to adult life stress. METHODS: A
      secondary analysis was conducted of a 2003 study of 176 hospital-based healthcare
      workers, which surveyed lifetime traumatic events, recent life events,
      psychological distress, coping, social support, and days off work due to stress
      or illness. RESULTS: Sixty eight percent (95% CI 61.1-74.9) of healthcare workers
      had one or more experience of violence, abuse or neglect, 33% (95% CI 26.1-40.0)
      before the age of 13. Compared to healthcare workers who did not experience
      childhood adversity, those who did reported more recent life events (median 11
      vs. 5 over the previous 6 months, p<.001) and greater psychological distress
      (median score 17 vs. 13, p<.001). The relationship between life events and
      psychological distress was not linear. Most healthcare workers without childhood
      adversity (73%) reported a low number of life events which were not associated
      with psychological distress. Most healthcare workers with childhood adversity
      (81%) reported a higher number of life events, for which the correlation between
      events and distress was moderately strong (Spearman's rho=.50, p<.001). Childhood
      adversity was also associated with more missed work days. Each of these outcomes
      was higher in 22 healthcare workers (13%) who had experienced more than one type
      of childhood adversity. CONCLUSIONS: Childhood adversity is common among
      healthcare workers and is associated with a greater number of life events, more
      psychological distress and impairment.

PMID- 20153052
TI  - Parental physical and psychological aggression.

PMID- 20153053
TI  - Maltreated and nonmaltreated children's evaluations of emotional fantasy.

PMID- 20153054
TI  - Kindergarten teachers' experience with reporting child abuse in Taiwan.
AB  - OBJECTIVE: The objectives were to examine factors associated with reporting child
      abuse among kindergarten teachers in Taiwan based on the Theory of Planned
      Behavior (TPB). METHOD: A stratified quota sampling technique was used to
      randomly select kindergarten teachers in Taiwan. The Child Abuse Intention Report
      Scale, which includes demographics, attitudes about child discipline, punishment
      for perpetrators, and professional responsibility for reporting, subjective norms
      regarding support for reporting from the general and specific important persons,
      perceived behavioral control, and vignettes of child abuse, was used to collect
      data. A total of 598 kindergarten teachers (return rate 47%) provided data.
      RESULTS: While 97% of teachers reported having no experience with reporting a
      child abuse case, 11% indicated they had failed to report a suspected case of
      child abuse. Multiple regression revealed that, except for social norms,
      attitudes toward child discipline, punishments for perpetrators, and professional
      responsibility as well as perceived behavioral control explained 22.4% of
      variance of kindergarten teachers' intention to report child abuse. CONCLUSIONS:
      With the exception of the subjective norms, the findings of this study supported
      the TPB that kindergarten teachers' intention to report child abuse is associated
      with attitudes toward child discipline, punishment for perpetrators, professional
      responsibility, and perceived behavioral controls over reporting. This study
      revealed the problem of underreporting child abuse among kindergarten teachers in
      Taiwan, and highlighted the discrepancy between child abuse training and expected
      reporting outcomes suggesting an insufficiency in the current training programs
      on child abuse. PRACTICE IMPLICATIONS: There is a need to scrutinize the current
      training in child abuse and develop standardized training and clear reporting
      guidelines that will increase kindergarten teachers' confidence when confronted
      with suspected victims and perpetrators of child abuse in Taiwan.

PMID- 20153055
TI  - Childhood trauma in substance use disorder and depression: an analysis by gender
      among a Brazilian clinical sample.
AB  - OBJECTIVE: In this study, we compared the frequency and intensity of childhood
      traumas in alcohol- or other drug-dependent patients, in patients with
      depression, and in a control group without psychiatric diagnoses. METHODS: The
      study had a retrospective design of a clinical sample of men and women from the
      groups listed above. They were evaluated by the same standardized instrument: the
      "Childhood Trauma Questionnaire." RESULTS: A higher frequency and intensity of
      emotional, physical, and sexual abuse were found in alcohol- and other drug
      dependent patients than in patients with depression, who, in turn, presented
      significantly higher proportions than the control group. In all of the cases, the
      frequency was higher among women than men. CONCLUSION: Because of the high
      frequency and intensity of childhood traumas among alcohol- or other drug
      dependent patients and depressed patients, the assessment of problems due to
      childhood traumas among these patients is essential to a better understanding of
      the etiology of those disorders and to their treatment.

PMID- 20153056
TI  - Comparison of population-level effects of heavy metals on fathead minnow
      (Pimephales promelas).
AB  - To evaluate the population-level effects of heavy metals (copper, zinc, cadmium,
      hexavalent chromium, nickel) on fathead minnow, Pimephales promelas, we first
      estimated the concentration-effect relationships between the metal concentrations
      and individual traits (juvenile survivability, hatchability, fertility) by using
      toxicity data collected from the literature. A Leslie matrix model of fathead
      minnow was used to calculate population growth rates from these relationships.
      The population threshold concentrations (PTCs) leading to zero net growth of the
      fish population were as follows: Cu, 27.4; Cd, 33.2; Zn (soft water), 81.5; Zn
      (hard water), 85.8; Ni, 504.8; Cr, 3251.6 (microg L(-1)). By comparing the PTCs
      with no observed effect concentrations (NOECs), we found that some PTCs were
      equivalent to or even lower than the corresponding NOECs. This result suggests
      that current ecological risk assessments based on the NOECs can be inadequate for
      protecting aquatic populations and more efforts on the population-level studies
      are needed.

PMID- 20153057
TI  - Ecotoxicological study on sediments of Mai Po marshes, Hong Kong using organisms
      and biomarkers.
AB  - Sediments from Mai Po Ramsar site, Hong Kong were in general shown to be highly
      toxic based on the results of four toxicity tests (Microtox solid-phase test,
      Daphnia mortality test, algal [Microcystis aeruginosa] growth inhibition test and
      ryegrass [Lolium perenne] seed germination/root elongation test). Sediment of the
      mudflat (which is open to Deep Bay, i.e., the pollution source) was the most
      toxic while sediment of gei wai 24g (an enclosed freshwater pond) was the least
      toxic. Results of biomarker studies (tilapia hepatic metallothionein; glutathione
      (GSH) and EROD activity using H4IIE rat hepatoma cell) were also concordant with
      those in the toxicity tests. Significant liner relationships (p<0.01) were found
      between GSH contents in the rat hepatoma cells and PAHs, OCPs contents in the
      sediment extracts. It is recommended that the present suite of bioassays is
      useful and is biologically relevant for future ecotoxicological studies focusing
      on similar wetlands.

PMID- 20153058
TI  - Identification and characterization of the major allergen of green bean
      (Phaseolus vulgaris) as a non-specific lipid transfer protein (Pha v 3).
AB  - BACKGROUND: Green bean (GB) has been reported to cause allergic reactions after
      ingestion, contact or inhalation of particles deriving from processing or
      cooking. Up-to-date no food allergens have been fully characterized in GB.
      OBJECTIVE: To characterize the GB major allergen(s) on a molecular level and to
      verify the involvement of non-specific lipid transfer proteins (nsLTPs) in GB
      allergy. METHODS: We recruited 10 Spanish patients reporting adverse reactions to
      GB. Skin prick tests, specific IgE detection and oral provocation were performed.
      Two nsLTP cDNAs were cloned from GB and over-expressed in Pichia pastoris. The
      recombinant LTPs (rLTPs) were characterized by circular dichroism spectroscopy
      and IgE-binding assays (immunoblotting and ELISA) with the patients' sera. Three
      natural LTPs (nLTPs) were further purified from GB fruit by chromatography. In
      vitro histamine release test was applied to compare the allergenic potency of
      rLTPs and nLTPs. RESULTS: Oral provocation test confirmed GB allergy. A 10kDa
      protein in GB extract was recognized by 80% of the sera and identified as nsLTP.
      The two rLTPs (named LTP1a and LTP1b), share 61.3% aa identity and present the
      typical nsLTP-like secondary structure. The IgE-binding and histamine release
      assays provided evidence that rLTPs and nLTPs possess different allergenic
      potency. CONCLUSIONS: nsLTP (Pha v 3) is the major allergen in GB and constitute
      a potential risk for patients affected by LTP-syndrome. GB encodes for several
      LTPs with different immune reactivity.

PMID- 20153061
TI  - Early temporal effects of three thyroid hormone synthesis inhibitors in Xenopus
      laevis.
AB  - Thyroid axis disruption is an important consideration when evaluating risks
      associated with chemicals. Bioassay methods that include thyroid-related
      endpoints have been developed in a variety of species, including amphibians,
      whose metamorphic development is thyroid hormone (TH)-dependent. Inhibition of TH
      synthesis in these species leads to developmental delay, and assays designed to
      capture these effects take several weeks to complete. In an effort to develop a
      shorter term approach, the early responses of various endpoints were evaluated in
      Xenopus laevis throughout 8d of exposure to three TH synthesis inhibitors:
      methimazole (100mg/L), 6-propylthiouracil (6-PTU) (20mg/L), and perchlorate (4
      mg/L). Endpoints included thyroid gland histology and cell numbers, circulating
      TH concentrations, and thyroidal TH and associated iodo-compounds. Thyroidal 3,5
      diodo-L-tyrosine (DIT) and thyroxine (T4) were significantly reduced from day 2
      onward by all three chemicals, while 3-monoiodo-L-tyrosine (MIT) was
      significantly reduced by methimazole and perchlorate, but not by 6-PTU. These
      reductions were the earliest indicators of TH synthesis inhibition. Histological
      effects were apparent on day 4 and became more exaggerated through day 8.
      However, reductions in circulating T4 and increases in thyroid gland cell numbers
      were not apparent until day 6. Reductions of thyroidal MIT, DIT, and T4 and
      circulating T4 are indicative of inhibitory effects of the chemicals on TH
      synthesis. Changes in thyroid histology and cell number represent compensatory
      effects modulated by circulating TSH. These observations establish a basis for
      the development of short term amphibian-based methods to evaluate thyroid axis
      effects using a suite of diagnostic endpoints.

PMID- 20153059
TI  - Progesterone treatment reduces disease severity and increases IL-10 in
      experimental autoimmune encephalomyelitis.
AB  - Ovarian hormones, including progesterone, are known to have immunomodulatory and
      neuroprotective effects which may alter the disease course of experimental
      autoimmune encephalomyelitis (EAE). In the current study, we examined the
      treatment potential of progesterone beginning at the onset of EAE symptoms.
      Progesterone treated animals showed reduced peak disease scores and cumulative
      disease indices, and decreased inflammatory cytokine secretion (IL-2 and IL-17).
      In addition, increased production of IL-10 was accompanied by increased numbers
      of CD19+ cells and an increase in CD8+ cells. Decreased chemokine and chemokine
      receptor expression in the spinal cord also contributed to decreased lesions in
      the spinal cord.

PMID- 20153060
TI  - Learning to see: patterned visual activity and the development of visual
      function.
AB  - To successfully interact with their environments, developing organisms need to
      correctly process sensory information and generate motor outputs appropriate to
      their size and structure. Patterned sensory experience has long been known to
      induce various forms of developmental plasticity that ultimately shape mature
      neural circuits. These same types of plasticity also allow developing organisms
      to respond appropriately to the external world by dynamically adapting neural
      circuit function to ongoing changes in brain circuitry and sensory input. Recent
      work on the visual systems of frogs and fish has provided an unprecedented view
      into how visual experience dynamically affects circuit function at many levels,
      ranging from gene expression to network function, ultimately leading to system
      wide functional adaptations.

PMID- 20153062
TI  - Safety and effectiveness of percutaneous coronary intervention (PCI) in elderly
      patients. a 5-year consecutive study of 201 cases with PCI.
AB  - The study objectives were to evaluate the safety and effectiveness of PCI in the
      elderly. The 201 cases with PCI were divided into the younger group (<60-year-old
      group, 33 cases), the old group (60- to 74-year-old group, 92 cases) and the very
      old group (75- to 89-year-old group, 76 cases). We found that the incidence of 2
      vessel disease, multi-vessel disease and complex lesions in the old and very old
      group was more frequent than that in the younger group (p<0.05, p<0.05, p<0.05).
      From the younger group to the very old group, the Gensini score increases
      significantly (40.50 vs. 42.00 vs. 45.25, p<0.05, p<0.01, p<0.01). The immediate
      success rate of PCI was 99.01% (199/201), and no significant difference was found
      in the three age groups. The complete revascularization in the very old group was
      much less than that in the old and younger groups. Logistic regression showed
      that only the incomplete revascularization was the independent risk factor of
      adverse events (odds ratio (OR)=2.14, 95% confidence interval (95%CI)=1.37-5.72).
      We conclude that in the elderly patients with favorable tolerance of PCI, PCI
      immediate success rate was similar to that of the young patients, suggesting that
      complete revascularization of the very old patients might improve the prognosis
      and reduce the incidence of cardiac events.

PMID- 20153063
TI  - Sunlight and health: attitudes of older people living in intermediate care
      facilities in southern Australia.
AB  - Older people have a high prevalence of falls and fractures, partly due to vitamin
      D deficiency. Sunlight is a major source of vitamin D, but many older people
      living in intermediate care facilities have inadequate sunlight exposure. The aim
      of this study was to determine the sun exposure practices and attitudes to
      sunlight in this population. Fifty-seven older residents of intermediate care
      facilities in Sydney, Australia were interviewed to determine their sun exposure
      practices, their views on sunlight and health and whether these have changed over
      their lives, factors affecting sunlight exposure and their knowledge of vitamin
      D. Sixty percent of the participants preferred to be outdoors, despite more than
      92% believing that sunlight was healthy. In their youth however, almost 90% had
      preferred to be outdoors. Poor health, physical constraints and a sense of lack
      of ownership of outdoor spaces were barriers to sunlight exposure. Improved
      physical access, more outdoor leisure activities and promotion of greater
      autonomy may improve safe and appropriate sunlight exposure in this population.

PMID- 20153064
TI  - Balloon valvuloplasty in the treatment of congenital aortic valve stenosis--a
      retrospective multicenter survey of more than 1000 patients.
AB  - BACKGROUND: The value of balloon valvuloplasty of the aortic valve in childhood
      is still under debate. OBJECTIVE: To evaluate the results of the procedure in a
      retrospective multicenter survey of a large cohort over a long time interval.
      METHODS: Retrospective analysis of 1004 patients with balloon valvuloplasty of
      the aortic valve performed between 9/1985 and 10/2006 at 20 centers in Germany,
      Austria and Switzerland. Amongst others, the following parameters were evaluated
      before and after the procedure as well as at the end of follow-up or before
      surgery: clinical status, left ventricular function, transaortic pressure
      gradient, degree of aortic regurgitation, freedom from re-intervention or
      surgery. PATIENTS: Patients from 1 day to 18 years of age with aortic valve
      stenosis were divided into four groups: 334 newborns (1-28 days); 249 infants (29
      365 days); 211 children (1-10 years), and 210 adolescents (10-18 years). RESULTS:
      Median follow-up was 32 months (0 days to 17.5 years). After dilatation the
      pressure gradient decreased from 65 (+/- 24)mm Hg to 26 (+/- 16)mm Hg and
      remained stable during follow-up. The newborns were the most affected patients.
      Approximately 60% of them had clinical symptoms and impaired left ventricular
      function before intervention. Complication rate was 15% in newborns, 11% in
      infants and 6% in older children. Independently of age, 50% of all patients were
      free from surgery 10 years after intervention. CONCLUSIONS: In this retrospective
      multicenter study, balloon valvuloplasty of the aortic valve has effectively
      postponed the need for surgery in infants, children and adolescents up to 18
      years of age.

PMID- 20153065
TI  - Cryptosporidium oocysts on fresh produce from areas of high livestock production
      in Poland.
AB  - Samples of fresh vegetables and soft fruit were collected from farmers' markets
      in the Lublin Area of Poland during 2006-2007; the produce was grown in areas of
      high to moderate livestock production. Cryptosporidium sp. oocysts were eluted
      from food surfaces, separated from residual food materials by IMS and identified
      by immunofluorescence and Nomarski differential interference contrast microscopy.
      Cryptosporidium sp. oocysts were detected in 6 of 128 vegetable samples (range 1
      47 oocysts), but not in any of 35 fruit samples. Both empty and intact oocysts
      were detected. Species identity of oocyst-positive samples was performed by
      molecular analysis at four genetic loci. One of two 18S rRNA loci amplified DNA
      from 5 of the 6 oocyst-positive samples, but insufficient DNA for RFLP or
      sequencing analysis was available from 4 of these samples. An oocyst-positive
      celery sample generated an RFLP pattern consistent with C. parvum at two loci,
      but insufficient DNA was available for subtyping (GP60 sequencing) this isolate.
      Oocyst-contaminated foods originated from districts with the highest numbers of
      homesteads possessing cattle herds and no contaminated produce was detected from
      districts containing lower numbers of cattle-owning homesteads, strengthening the
      assumption that the origin of the contamination was livestock. The results of
      this study strengthen the evidence for the potential for zoonotic foodborne
      transmission of Cryptosporidium.

PMID- 20153066
TI  - Impact of pooling powdered infant formula samples on bacterial evolution and
      Cronobacter detection.
AB  - Enterobacter sakazakii has been identified as the causative agent of serious
      neonatal infections, associated with high mortality rates. In most cases,
      powdered infant formula (PIF) has been identified as the source of infection.
      Recently, strains commonly referred to as E. sakazakii were proposed for
      classification in a new genus, Cronobacter. The standardised method for detection
      of Cronobacter in PIF (ISO/TS 22964; IDF/RM 210) involves pre-enrichment in
      buffered peptone water (BPW), followed by selective enrichment and plating onto
      ESIA chromogenic agar. For greater convenience and to reduce analysis cost, the
      common practice in the food industry is to pool samples at a constant dilution
      rate, in order to perform a single pre-enrichment and subsequent analysis. The
      consequences on the sensitivity of Cronobacter detection are not evident. We
      evaluated the impact of pooling on the growth of Cronobacter and PIF background
      microflora in samples undergoing pre-enrichment culturing in BPW. Growth of the
      pathogen was monitored by direct plating onto selective agar or by using a
      recently developed sensitive enumeration method, based on membrane filtration
      followed by transfer of the filter onto the selective agar. The evolution of the
      total bacterial population of the PIF was monitored from a qualitative and
      quantitative point, using molecular or classical microbiological methods. Results
      showed that pooling had a negative impact on the maximum population of
      Cronobacter attained, whereas no clear effect was observed on the onset of
      growth. This observation suggests strong bacterial interactions with the PIF
      background microflora, confirmed by a generally higher background microflora
      growth potential in PIF samples from various origins. These important findings
      suggest that, in some cases, the practice of pooling samples may affect the
      performance of the detection method.

PMID- 20153067
TI  - Germinant receptor diversity and germination responses of four strains of the
      Bacillus cereus group.
AB  - Four strains of the Bacillus cereus group were compared for their germinant
      receptor composition and spore germination capacity. Phylogenetic analysis of the
      germinant receptor encoding operons of the enterotoxic strains B. cereus ATCC
      14579 and ATCC 10987, the emetic strain AH187, and the psychrotolerant strain
      Bacillus weihenstephanensis KBAB4, indicated a core group of five germinant
      receptor operons to be present in the four strains, with each strain containing
      one to three additional receptors. Using quantitative PCR, induction of
      expression during sporulation was confirmed for all identified germinant receptor
      operons in these strains. Despite the large overlap in receptors, diversity in
      amino acid-induced germination capacity was observed, with six out of 20 amino
      acids, serving as germinants for spores of all four strains. Each strain showed
      unique features: efficient germination of strain KBAB4 spores required non
      inducing amounts of inosine as the co-germinant, strain ATCC 10987 spores
      germinated only efficiently after heat activation. Furthermore, strain ATCC 14579
      and AH187 spores germinated without heat activation or inosine, with strain ATCC
      14579 spores being triggered by all amino acids except phenylalanine and strain
      AH187 spores being specifically triggered efficiently only by phenylalanine.
      Analysis of all germination data did not reveal strict linkages between specific
      germinants and germinant receptors. Finally, the diversity in nutrient-induced
      germination capacity was also reflected in the diverse germination responses of
      heat-activated spores of the four B. cereus strains in food matrices, such as
      milk, rice water and meat bouillon, indicating that amino acid composition and/or
      availability of inosine are important germination determinants in foods.

PMID- 20153068
TI  - Inhibition of verocytotoxigenic Escherichia coli in model broth and rumen systems
      by carvacrol and thymol.
AB  - The antimicrobial activities of thymol and carvacrol were assessed against a
      selection of verocytotoxigenic Escherichia coli (VTEC) strains (n=11) and other
      bacterial species and spoilage bacteria (n=7) using a model broth system. The
      effects of pH, temperature, water activity, sodium chloride concentrations,
      inoculum size and the presence of competing microflora on the activities of
      thymol and carvacrol against E. coli O157:H7 strain 380-94 were also determined.
      The minimum inhibitory and bactericidal concentrations (MIC and MBC,
      respectively) and numbers of surviving E. coli O157:H7 were determined following
      incubation. The mean numbers of VTEC surviving exposure to thymol or carvacrol at
      concentrations of >/=500mug/ml were between 2.0 and 7.8log cfu/ml less than the
      numbers in the corresponding controls. The susceptibility of E. coli O157:H7 to
      carvacrol or thymol was found to increase with decreasing storage temperature,
      water activity, pH and E. coli O157:H7 inoculum size. Sodium chloride (0.5-2.5%)
      and the presence of a microflora cocktail did not significantly (p>0.05) affect
      the antimicrobial activities of thymol or carvacrol against E. coli O157:H7. The
      antimicrobial activity of carvacrol against E. coli O157:H7 was also tested in a
      model rumen system. A MIC of 500mug/ml carvacrol reduced E. coli O157:H7
      inoculated at levels of 10(3) and 10(6)cfu/ml to undetectable levels in the
      system after 24h incubation. This concentration of carvacrol significantly
      (p<0.05) decreased the total gas production and volatile fatty acid
      concentrations in the model rumen assay.

PMID- 20153069
TI  - Molecular characterization of diarrheagenic Escherichia coli strains from stools
      samples and food products in Colombia.
AB  - The prevalence of diarrheagenic Escherichia coli in childhood diarrhea and the
      role of contaminated food products in disease transmission in Colombia are
      largely unknown. The aim of this study is to identify E. coli pathotypes,
      including E. coli O157:H7, from 108 stool samples from children with acute
      diarrhea, 38 meat samples and 38 vegetable samples. Multiplex PCR and Bax Dupont
      systems were used for E. coli pathotype detection. Eighteen (9.8%) E. coli
      diarrheagenic pathotypes were detected among all clinical and food product
      samples tested. Four different pathotypes were identified from clinical samples,
      including enteroaggregative E. coli, enterotoxigenic E. coli, shiga-toxin
      producing E. coli, and enteropathogenic E. coli. Food product samples were
      positive for enteroaggregative and shiga-toxin producing E. coli, suggesting that
      meat and vegetables may be involved in transmission of these E. coli pathotypes
      in the community. Most E. coli strains identified belong to the phylogenetic
      groups A and B1, known to be associated with intestinal rather than
      extraintestinal E. coli clones. Our data is the first molecular E. coli report
      that confirms the presence of E. coli pathotypes circulating in Colombia among
      children with diarrhea and food products for human consumption. Implementation of
      multiplex PCR technology in Latin America and other countries with limited
      resources may provide an important epidemiological tool for the surveillance of
      E. coli pathotypes from clinical isolates as well as from water and food product
      samples.

PMID- 20153070
TI  - Food-borne diseases - the challenges of 20 years ago still persist while new ones
      continue to emerge.
AB  - The burden of diseases caused by food-borne pathogens remains largely unknown.
      Importantly data indicating trends in food-borne infectious intestinal disease is
      limited to a few industrialised countries, and even fewer pathogens. It has been
      predicted that the importance of diarrhoeal disease, mainly due to contaminated
      food and water, as a cause of death will decline worldwide. Evidence for such a
      downward trend is limited. This prediction presumes that improvements in the
      production and retail of microbiologically safe food will be sustained in the
      developed world and, moreover, will be rolled out to those countries of the
      developing world increasingly producing food for a global market. In this review
      evidence is presented to indicate that the microbiological safety of food remains
      a dynamic situation heavily influenced by multiple factors along the food chain
      from farm to fork. Sustaining food safety standards will depend on constant
      vigilance maintained by monitoring and surveillance but, with the rising
      importance of other food-related issues, such as food security, obesity and
      climate change, competition for resources in the future to enable this may be
      fierce. In addition the pathogen populations relevant to food safety are not
      static. Food is an excellent vehicle by which many pathogens (bacteria,
      viruses/prions and parasites) can reach an appropriate colonisation site in a new
      host. Although food production practices change, the well-recognised food-borne
      pathogens, such as Salmonella spp. and Escherichia coli, seem able to evolve to
      exploit novel opportunities, for example fresh produce, and even generate new
      public health challenges, for example antimicrobial resistance. In addition,
      previously unknown food-borne pathogens, many of which are zoonotic, are
      constantly emerging. Current understanding of the trends in food-borne diseases
      for bacterial, viral and parasitic pathogens has been reviewed. The bacterial
      pathogens are exemplified by those well-recognized by policy makers; i.e.
      Salmonella, Campylobacter, E. coli and Listeria monocytogenes. Antimicrobial
      resistance in several bacterial food-borne pathogens (Salmonella, Campylobacter,
      Shigella and Vibrio spp., methicillin resistant Staphylcoccus aureas, E. coli and
      Enterococci) has been discussed as a separate topic because of its relative
      importance to policy issues. Awareness and surveillance of viral food-borne
      pathogens is generally poor but emphasis is placed on Norovirus, Hepatitis A,
      rotaviruses and newly emerging viruses such as SARS. Many food-borne parasitic
      pathogens are known (for example Ascaris, Cryptosporidia and Trichinella) but few
      of these are effectively monitored in foods, livestock and wildlife and their
      epidemiology through the food-chain is poorly understood. The lessons learned and
      future challenges in each topic are debated. It is clear that one overall
      challenge is the generation and maintenance of constructive dialogue and
      collaboration between public health, veterinary and food safety experts, bringing
      together multidisciplinary skills and multi-pathogen expertise. Such
      collaboration is essential to monitor changing trends in the well-recognised
      diseases and detect emerging pathogens. It will also be necessary understand the
      multiple interactions these pathogens have with their environments during
      transmission along the food chain in order to develop effective prevention and
      control strategies.

PMID- 20153071
TI  - The detection and influence of food soils on microorganisms on stainless steel
      using scanning electron microscopy and epifluorescence microscopy.
AB  - A range of food soils and components (complex [meat extract, fish extract, and
      cottage cheese extract]; oils [cholesterol, fish oil, and mixed fatty acids];
      proteins [bovine serum albumin (BSA), fish peptones, and casein]; and
      carbohydrates [glycogen, starch, and lactose]) were deposited onto 304 2B finish
      stainless steel surfaces at different concentrations (10-0.001%). Scanning
      electron microscopy (SEM) and epifluorescence microscopy were used to visualise
      the cell and food soil distribution across the surface. Epifluorescence
      microscopy was also used to quantify the percentage of a field covered by cells
      or soil. At 10% concentration, most soils, with the exception of BSA and fish
      peptone were easily visualised using SEM, presenting differences in gross soil
      morphology and distribution. When soil was stained with acridine orange and
      visualised by epifluorescence microscopy, the limit of detection of the method
      varied between soils, but some (meat, cottage cheese and glycogen) were detected
      at the lowest concentrations used (0.001%). The decrease in soil concentration
      did not always relate to the surface coverage measurement. When 10% food soil was
      applied to a surface with Escherichia coli and compared, cell attachment differed
      depending on the nature of the soil. The highest percentage coverage of cells was
      observed on surfaces with fish extract and related products (fish peptone and
      fish oil), followed by carbohydrates, meat extract/meat protein, cottage
      cheese/casein and the least to the oils (cholesterol and mixed fatty acids).
      Cells could not be clearly observed in the presence of some food soils using SEM.
      Findings demonstrate that food soils heterogeneously covered stainless steel
      surfaces in differing patterns. The pattern and amount of cell attachment was
      related to food soil type rather than to the amount of food soil detected. This
      work demonstrates that in the study of conditioning film and cell retention on
      the hygienic properties of surfaces, SEM may not reveal the presence of retained
      conditioning film, and thus methods such as epifluorescence microscopy should
      also be used. This is an essential facet to the methodology design of future work
      carried out in our laboratories on the effectiveness of the removal of cells and
      conditioning films from surfaces using different cleaning regimes.

PMID- 20153072
TI  - Prevalence of metabolic syndrome and optimal waist circumference cut-off points
      for adults in Beijing.
AB  - BACKGROUND: In the modified ATP III definition for metabolic syndrome (MS), the
      cut-off values for central obesity were set to > or =90 cm for male and > or =80
      cm for women. Recently, a new Chinese definition for central obesity was set to >
      or =90 cm for male and > or =85 cm for women according to the corresponding BMI
      value of 25 kg/m(2). OBJECTIVE: The purpose of this study was to explore the
      optimal WC cut-off points to reflect the cluster of multiple risk factors for
      adults in Beijing. METHOD: The data collected during the surveillance of risk
      factors for non-communicable diseases in Beijing 2005 were used, with a total of
      16,711 adults studied. Subjects with two or more components from the modified ATP
      III definition other than central obesity were considered to have multiple risk
      factors. RESULTS: The optimal WC cut-off points were 87 cm in men and 80 cm for
      women. When applied the WC advised definition for MS, the age-standardized
      prevalence was 38.0% for male and 32.3% for women, which is significantly higher
      than using the original one for men (34.7% vs 32.3%, P<0.001). CONCLUSION: The
      present study indicated that optimal waist circumference cut-off points were
      lower than that proposed in the modified ATP III definition, especially for men.

PMID- 20153073
TI  - Interspecific information transfer influences animal community structure.
AB  - Acquiring information from the cues and signals of other species of the same
      trophic level is widespread among animals, and can help individuals exploit
      resources and avoid predators. But can such interspecific information transfer
      also influence the spatial structure of species within communities? Whereas some
      species use heterospecific information without changing their position, we review
      research that indicates that heterospecific information is a driving factor in
      the formation or maintenance of temporary or stable mixed-species groups.
      Heterospecific information can also influence the organization of such groups,
      including leadership. Further, animals sometimes select habitats using
      heterospecific information. We survey interspecific information transfer, and
      evaluate the morphological, ecological and behavioral factors that make some
      species information sources and others information seekers.

PMID- 20153074
TI  - Infection: a hypothesis on active susceptibility and species immunity with
      implications for AIDS prevention.
AB  - There is no fundamental difference in contagiousness or pathogenicity between the
      normal and pathogenic microfloras: both are contagious, and both may either cause
      illness or persist in the body of a healthy carrier. The contagiousness of the
      normal microflora is determined by its positive function in the host. In addition
      to the normal microflora, endogenous retrovirus genes are also useful for a
      macroorganism: they have been found to be integral elements of many animal and
      plant genomes and participate in vital functions, such as genome activity
      control, antiviral defense, and formation of the placenta; dysfunction of some
      endogenous retrovirus genes causes pathology. Components of bacterial cells cause
      protective effects with respect to noninfectious somatic diseases. Therefore, it
      is reasonable to assume that natural susceptibility to both "normal" and
      "pathogenic" microfloras results from vital necessity for a macroorganism to
      interact with them. The necessity to interact with specific microorganisms and,
      hence, susceptibility to them is the cause of their infectivity. In this
      connection, studies on the positive functions of specific "pathogenic" microflora
      in a macroorganism with the use of SPF animals would be of interest. Even more
      interesting would be experiments with transfer of specific microbial genes into
      the genomes of susceptible species, which may help to understand the causes and
      mechanisms of susceptibility/insusceptibility as a basis of species immunity and
      develop fundamentally new and more natural methods for preventing and treating
      infectious diseases.

PMID- 20153076
TI  - Interaction between cytokines, cannabinoids and the nervous system.
AB  - Cytokines play important roles in neuroinflammation and neurodegeneration. The
      endocannabinoid system (ES) is comprised of the CB1 and CB2 cannabinoid
      receptors, endogenous ligands, and proteins involved in endocannabinoid synthesis
      and inactivation. The ES participates in the regulation of immune responses in
      the nervous system. Activation of the cannabinoid system is associated with
      therapeutic effects that may be mediated by the down-regulation of cytokine
      expression. Here we review the findings from studies on the reciprocal regulation
      of the immune and cannabinoid systems, which is based on functional as well as
      anatomical connections. We then discuss mechanisms involved in the reciprocal
      regulation of cytokines and the ES.

PMID- 20153075
TI  - Minocycline differentially modulates macrophage mediated peripheral immune
      response following Japanese encephalitis virus infection.
AB  - Japanese encephalitis virus (JEV) is a neurotropic flavivirus that is the
      causative agent of a major mosquito-borne encephalitis in the world. Evasion of
      peripheral immune system facilitates the entry of the virus into the central
      nervous system (CNS) where it causes extensive neuronal inflammatory damage that
      leads to death or severe neuropschychiatric sequel in survivors. It has been
      proposed that after entry into the body, the virus is carried into the CNS by
      peripheral immune cells that act as Trojan horses. In this study we investigate
      whether macrophages can be considered as such a Trojan horse. We also investigate
      the role of minocycline, a synthetic tetracycline, in such processes. Minocycline
      has been found to be broadly protective in neurological disease models featuring
      inflammation and cell death but there has been no report of it having any
      modulatory role in peripheral macrophage-mediated immune response against viral
      infection. Persistence of internalized virus within macrophages was visualized by
      immunofluorescent staining. Cytotoxicity assay revealed that there was no
      significant cell death after 24 h and 72 h infection with JEV. Proinflammatory
      cytokine levels were elevated in cells that were infected with JEV but it was
      abrogated following minocycline treatment. Reactive oxygen species level was also
      increased after JEV infection. Nitric oxide level was found to increase after 72
      h post infection but remained unchanged after 24h. The cellular levels of
      signaling molecules such as PI3 kinase, phophoAkt and phospho p38MAP kinase were
      found to be altered after JEV infection and minocycline treatment. JEV infection
      also affected the VEGF-MMP pathway. Increased activity of MMP-9 was detected from
      JEV-infected macrophage culture supernatants after 72 h; minocycline treatment
      resulted in reduced activity. Thus it seems that minocycline dampens peripheral
      immune reactions by decreasing proinflammatory cytokine release from infected
      macrophages and the virus survives within macrophages long enough to be carried
      into the CNS, even though minocycline inhibits cell survival.

PMID- 20153077
TI  - Cannabinoids and the immune system: an overview.
AB  - Cannabinoids can influence the immune network. Data on the impact of exogenous
      cannabinoid ligands on immune function serve not only to understand how the
      endocannabinoid system modulates immune phenomena associated with infection or
      inflammation, but also to identify therapeutic targets for immune diseases.
      Cannabinoids can modulate immune reactions in the periphery but also in the
      brain, influence T cell subset balance and cytokine expression and play a role in
      the balance between neuroinflammation and neurodegeneration. Immune cells can
      synthesize endocannabinoids and also be influenced by cannabinoid analogues.
      Cannabinoid receptors show different expression on immune cells depending on
      activation status and stimuli. The complexity of relation between cannabinoid
      ligands of various classes and cannabinoid receptors brought the need to refine
      the simple conceptual frame of agonist-antagonists and offered potential
      implications for understanding interactions in pathological conditions. The
      immune influence of cannabinoid ligands is not fully elucidated. However, aspects
      of their immunomodulatory effects provide the basis for a context-dependent
      targeted therapeutic approach, thus leading to the possibility for the use of
      cannabinoids in the treatment of inflammatory disease.

PMID- 20153078
TI  - Periorbital mucinosis: a variant of cutaneous lupus erythematosus?
AB  - Lupus erythematosus has a wide spectrum of cutaneous manifestations, including
      periorbital mucinosis. We report 3 cases of periorbital mucinosis occurring in
      association with other cutaneous signs of lupus erythematosus. Based on a review
      of the literature, periorbital mucinosis is a rare and not widely recognized
      clinical manifestation of the disease. Although unusual, familiarity with
      periorbital mucinosis as a manifestation of lupus erythematosus broadens our
      understanding of these entities and expands the spectrum of cutaneous lupus
      erythematosus.

PMID- 20153079
TI  - Bisphosphonate-related osteonecrosis of the jaw presenting as a cutaneous dental
      sinus tract: a case report and review of the literature.
AB  - Bisphosphonates are endogenous pyrophosphate analogs that work to inhibit
      osteoclast activity. They are commonly used in the treatment of patients with
      bone related diseases, such as solid tumor metastasis and osteoporosis. One of
      the infrequent but not rare side effects, especially with high doses of
      bisphosphonates, is osteonecrosis of the jaw. Although predominantly recognized
      by dentists because of the bony and intraoral manifestations of the disease, it
      may also present on the skin. We present a case of osteonecrosis of the jaw
      resembling two flesh-colored papules associated with dental sinus tracts to
      highlight the clinical manifestations that dermatologists may encounter, and
      review the literature on this rare but morbid condition.

PMID- 20153080
TI  - Continuing diarrhoea after ten days of oral metronidazole or oral vancomycin for
      presumed, hospital-acquired Clostridium difficile colitis in elderly hospital
      patients.

PMID- 20153081
TI  - Evidence from a UK teaching hospital that MRSA is primarily transmitted by the
      hands of healthcare workers.

PMID- 20153082
TI  - Molecular epidemiology of MRSA among nasal carriers in a tertiary care hospital:
      first report from Nepal.

PMID- 20153083
TI  - Funnel plots should become the standard methodology to identify centres deserving
      further scrutiny.

PMID- 20153084
TI  - Redox agents modulate neuronal activity and reproduce physiological aspects of
      neuronal aging.
AB  - The high oxygen consumption and post-mitotic nature of the central nervous system
      (CNS) makes it particularly susceptible to oxidative stress, the impact of which
      is widely regarded as a root cause of functional impairment of the aging brain in
      vertebrates and invertebrates alike. Using an invertebrate model system we
      demonstrate that the lipid soluble antioxidant alpha-tocopherol can both reverse
      2,2-azobis(2-methylpropion-amidine) dihydrochloride (AAPH) induced decline in
      excitability in young neurons as well as restore the electrical activity and
      excitability of aged neurons not unlike the level of their younger equivalents.
      Furthermore, using two analogs of alpha-tocopherol where either the acyl chain
      has been removed (Trolox) or the hydroxyl group of the chromanol ring has been
      methylated we were able to assert that the restorative effect of alpha-tocopherol
      requires both insertion into the plasma membrane as well as an active OH group.
      Thus, our results indicate peroxidation is an important modulator of neuronal
      excitability as well as support the growing body of evidence suggesting alpha
      tocopherol's actions may extend well beyond its established role as a lipid
      domain preventative antioxidant.

PMID- 20153085
TI  - [High volume hemofiltration in septic shock].
AB  - Severe sepsis and septic shock are conditions associated with high morbidity and
      mortality. The disproportionate release of pro-inflammatory and anti-inflammatory
      mediators caused by the septic insult is the promoter of multiple organ
      dysfunction. Conventional hemodialysis, hemofiltration or a combination of both
      can be a good option to replace the deteriorating renal function in critically
      ill patients by the removal of nitrogen compounds (small molecules). However,
      this "renal dose" is insufficient for the removal of inflammatory mediators
      (medium molecules), and therefore contributes little to the cardiovascular
      stabilization of patients with septic shock. In this setting, a higher dose of
      ultrafiltration (> 50 ml/kg/h) or "septic dose" may be needed. In this review
      article, we have analyzed the clinical and pathophysiological rationale for the
      use of high volume hemofiltration in patients with septic shock.

PMID- 20153086
TI  - [Apparent brain death after a baclophen overdose].

PMID- 20153087
TI  - [Erythematous nodules in a patient receiving hemodialysis].

PMID- 20153088
TI  - [Evaluation of CHROmagar orientation medium for the detection of Streptococcus
      agalactiae in pregnant women].

PMID- 20153089
TI  - 3D-QSAR studies on quinazoline antifolate thymidylate synthase inhibitors by
      CoMFA and CoMSIA models.
AB  - Thymidylate synthase (TS) is a crucial enzyme for DNA biosynthesis and many
      nonclassical lipophilic antifolates targeting this enzyme are quite efficient and
      encouraging as antitumor drugs. Herein, we report some 3D-QSAR analyses using
      CoMFA and CoMSIA on quinozoline antifolates in order to have a better
      understanding of the mechanism of action and structure-activity relationship of
      these compounds. By applying leave-one-out (LOO) cross-validation study, we
      obtained cross-validated q(2) value of 0.573 for CoMFA and 0.445 for CoMSIA,
      while the non-cross-validated r(2) values for them were found to be 0.935 and
      0.893, respectively. The models were graphically interpreted using CoMFA and
      CoMSIA contour plots. The results obtained from this study could be used for
      rational design of potent inhibitors against thymidylate synthase.

PMID- 20153090
TI  - Synthesis of 3-((2,4-dichlorophenoxy)methyl)-1,2,4-triazolo(thiadiazoles and
      thiadiazines) as anti-inflammatory and molluscicidal agents.
AB  - A series of fused and non fused 1,2,4-triazoles with (2,4-dichlorophenoxy) moiety
      are prepared utilizing 3-((2,4-dichlorophenoxy)methyl)-4-amino-4H-1,2,4-triazole
      5-thiol (3). The latter on reaction with carboxylic acids, ethylchloroformate,
      ethylcyanoacetate and sodium nitrite gives five membered fused triazole
      derivatives 4a-d, 5, 6, 7 and 10, respectively. The six membered heterocycles 11,
      12 and 14 are prepared by cyclization of compound 3 with phenacyl bromide,
      chloroacetic acid and alpha-bromoketone respectively. Most of the newly
      synthesized compounds were screened for their anti-inflammatory and molluscicidal
      activities. The compounds 4b, 4d, 11 and 14 showed potent anti-inflammatory
      activities in dose dependent manner while compounds 3, 4b, 8 and 10 exhibited
      promising molluscicidal activities.

PMID- 20153091
TI  - [Hyponatremia: from physiopathology to practice].
AB  - Hypotonic hyponatremia is the most common electrolyte abnormality encountered in
      hospitalized patients. It is often asymptomatic but associated with increased
      mortality and morbidity. Prompt recognition of the underlying cause using a
      systematic physiology based approach and careful evaluation the chronicity of the
      hyponatremia is mandatory for an optimal management. One should first document
      hypotonicity, and then assess the renal response to hypotonicity to exclude water
      intoxication, and the extracellular volumes. The further step will identify
      hyponatremia due to volemic stimulation of vasopressin associated to
      extracellular dehydration (corrected by isotonic saline infusion) or to
      oedematous states. After exclusion of hypocorticism and hypothyroidism, one would
      conclude to inappropriate secretion of antidiuretic hormone whose etiology would
      have to be established. The use of hypertonic saline solutions should be
      restricted to the treatment of acute and severe hyponatremia with evidence of
      brain damage. Chronic hyponatremia should be correct slowly to avoid the risk of
      osmotic demyelination syndrome. Water restriction is commonly recommended in
      inappropriate secretion of antidiuretic hormone or in hypervolemia with a
      questionable effectiveness. The recent development of vasopressin receptor
      antagonists (vaptans) will modify our therapeutic approaches. Yet, further
      studies are needed to document their additional impact on morbidity and
      mortality.

PMID- 20153092
TI  - [Infectious aortic aneurysms. A case series of 10 patients].
AB  - PURPOSE: Infectious aortic aneurysms are rare, being responsible of less than 3%
      of aortic aneurysms. In this study, we report the clinical characteristics and
      the outcome of patients presenting with infectious aortic aneurysms in an
      internal medicine unit. METHODS: Diagnosis of infection-related aortic aneurysm
      was obtained using: computed tomographic scan; and blood cultures, cultures and
      molecular biology testing of aortic wall and intra-aneurismal thrombus. RESULTS:
      The 10 consecutive patients included in this study consisted in eight men and two
      women with a mean age of 61.7 years. Patients presented with fever (n=9),
      asthenia (n=2), abdominal (n=4) or chest pain (n=1), lumbar pain (n=3). Computed
      tomographic scan showed aneurysm involving both thoracic and abdominal aorta
      (n=1), abdominal (n=8) or thoracic aorta (n=1). Isolated microorganisms were:
      positive Gram cocci (70%) and negative Gram bacilli (30%). All patients underwent
      both medical and surgical therapy. Outcome was favorable in nine patients; the
      remaining patient died from aneurismal aortic rupture. CONCLUSION: Clinical
      manifestations revealing infectious aortic aneurysms are variable, including
      aneurysm rupture as well as atypical abdominal pain with inflammatory syndrome.
      These latter presentations are more common in patients, who are hospitalized in
      internal medicine. Our study underlines that this clinical pattern should not be
      ignored, in order to avoid both diagnostic and therapeutic delay that could lead
      to life-threatening complications and poor prognosis.

PMID- 20153093
TI  - [Extracorporeal photochemotherapy or immunotherapy using cells modified by
      photochemistry].
AB  - Extracorporeal photochemotherapy (ECP) is an autologous cell therapy used for the
      treatment of diseases involving pathogenic cells: cutaneous T-cell lymphoma,
      organ rejection and graft versus host disease. During an ECP procedure, patients
      receive a cellular product consisting of autologous mononuclear cells, containing
      the pathogenic cells, treated with a photosensitising agent and an UV-A
      radiation. The aim of the treatment is to induce a specific immune reaction
      modulating the activity of untreated pathogenic lymphocytes responsible for the
      disease and therefore an improvement of clinical manifestations. The precise
      mechanisms of action remain to be defined in humans. Its efficacy coupled with
      the absence of side effects could lead to decrease the use of immunosuppressive
      drugs. PCE appears as an immunotherapy using cells modified by photochemistry,
      which allows specific immune modulation of pathogenic lymphocytes.

PMID- 20153094
TI  - [Systemic sarcoidosis after treatment with pegylated interferon-alpha].
AB  - A few cases of sarcoidosis have been reported in the course of chronic hepatitis
      C, with or without alpha-interferon treatment. We report a 54-year-old woman who
      presented a typical sarcoidosis in this context. The sarcoidosis involved skin,
      lungs and eyes. There are data in the literature supporting a pathogenic link
      between alpha-interferon and sarcoidosis: alpha-interferon possessing a non
      specific immunologic inductor. The treatment of the sarcoidosis in this context
      is difficult and has to be adjusted to both the severity of the sarcoidosis and
      the viral hepatitis. Although sarcoidosis induced by alpha-interferon is rare,
      clinicians must be aware of this association.

PMID- 20153096
TI  - The WHO surgical safety checklist: are we measuring up?

PMID- 20153095
TI  - Is an appropriate cutoff of hypertriglyceridemic waist designated for type 2
      diabetes among Chinese adults?
AB  - BACKGROUND & AIMS: We aimed to estimate appropriate cutoff of
      hypertriglyceridemic waist (HTGW) designated for impaired fasting glucose
      (IFG)/diabetes mellitus (DM) and to evaluate the association between HTGW and
      fasting glucose, IFG and DM, respectively. METHODS: A cross-sectional survey in a
      nationally representative sample of 15,540 Chinese adults aged 35-74 years was
      conducted during 2000-2001. RESULTS: Appropriate cutoffs of HTGW designated both
      for IFG and DM was triglyceride> or =110mg/dl and waist circumference> or =75cm
      both among men and women. Overall 35.4% of men as well as 33.6% of women had
      HTGW. Moreover 30.8%, 7.2% of men with HTGW as well as 30.0%, 9.7% of women had
      IFG and DM, respectively. Furthermore multivariate models revealed that adjusted
      odds ratios of IFG and DM were 2.7 (1.7, 2.5) and 2.6 (1.8, 3.8) for men with
      HTGW as well as 1.7 (1.4, 2.1) and 3.6 (2.5, 5.1) for women, respectively.
      CONCLUSIONS: As the phenotype of visceral obesity HTGW was more common among
      Chinese adults. Global lifestyle modification should be targeted at adults with
      HTGW to prevent the premature incidence of DM and reduce the burden in future in
      China.

PMID- 20153097
TI  - Novel agents for B-cell non-Hodgkin lymphoma: science and the promise.
AB  - There has been tremendous insight gained in the last two decades from basic
      science research. New molecular targets in neoplastic cells are emerging and
      provide the rationale for clinical development of novel agents in non-Hodgkin
      lymphoma. These novel agents can be broadly categorized into two groups. The
      first is by immunotherapy which includes novel monoclonal antibodies and
      immunomodulating drugs, which takes advantage of or optimizes immune system
      function. The other group of drugs target small molecules that may play an
      important role in tumorigenesis. The mechanisms of anti-tumor activity include
      targeting apoptotic pathways, inhibition of proteasomes, mammalian target of
      rapamycin (mTOR), cyclin-dependent kinases and histone deacetylases. The purpose
      of this review is to focus on these novel agents and the various treatment
      approaches that are currently being evaluated in non-Hodgkin lymphoma.

PMID- 20153098
TI  - Perfluorochemicals in wastewater treatment plants and sediments in Hong Kong.
AB  - The study reported in this paper examined the concentrations of nineteen
      perfluorochemicals (PFCs), including perfluoroalkyl sulfonates, carboxylates, and
      sulfonamides in samples collected from Hong Kong wastewater treatment plants
      (WWTPs) and sediments. The study was the first to use an external isolator column
      to assist in the quantification of PFCs in environmental samples without having
      to make internal modifications to a liquid chromatography system.
      Perfluorooctanesulfonate was found to be the dominant PFC pollutant in Hong Kong,
      and the WWTP sludge was the major sink of PFCs discharged from the urban areas.
      Compared to discharge influenced by industrial activities, much less
      perfluorooctanoate was found in waste streams. The significantly lower level of
      perfluorodecanesulfonate in WWTP sludge reflects the important influence of
      consumer products on PFC distribution. The dominance of even-chain length
      perfluoroalkyl carboxylates in all of the WWTP sludge samples investigated
      further suggests the strong aerobic degradation of fluorotelomer alcohols in
      WWTPs.

PMID- 20153099
TI  - Theoretical study for regulatory property of scaffold protein on MAPK cascade: a
      qualitative modeling.
AB  - An integrated mathematical model, which incorporates scaffold proteins into a
      mitogen-activated protein kinases cascade, is constructed. By employing Monte
      Carlo simulation, regulatory property of scaffold protein on signaling ability
      for the mitogen-activated protein kinases cascade is investigated theoretically.
      It is found that (i) scaffold binding increases signal amplification if
      dephosphorylation is slow and decreases amplification if dephosphorylation is
      rapid. Also, increasing the number of scaffold decreases amplification if
      dephosphorylation is slow. (ii) The scaffold number can control the timing of
      kinase activation so that the time flexibility of signaling is enhanced. (iii) It
      is observed that for slow dephosphorylation case, scaffolds decrease the
      sharpness of the dose-response curves. While for fast dephosphorylation case,
      increasing scaffold number decreases the height of response, but the shape of
      graded response is sustained. Furthermore, the underlying mechanism and the
      correlation of our results with real biological systems are clarified.

PMID- 20153100
TI  - Suppression of IAPP fibrillation at anionic lipid membranes via IAPP-derived
      amyloid inhibitors and insulin.
AB  - Aggregation of human islet amyloid polypeptide (hIAPP) into cytotoxic beta-sheet
      oligomers and amyloid plaques is considered a key event in pancreatic beta-cell
      degeneration in type 2 diabetes (T2D). hIAPP is synthesized in the pancreatic
      beta-cells and it is stored, co-processed in the secretory granules, and co
      secreted to the extracellular matrix together with insulin. In vivo, hIAPP
      aggregation may start and proceed at the water-cell membrane interface and
      anionic lipid membranes strongly enhance the process of hIAPP fibrillization
      which is causally linked to membrane disintegration and cell degeneration. In
      this study we explored the amyloidogenic propensity and conformational properties
      of hIAPP in the presence of negatively charged membrane (DOPC/DOPG phospholipid
      bilayers) surfaces upon addition of two recently designed potent hIAPP-derived
      inhibitors of hIAPP amyloidogenesis, the hexapeptide NF(N-Me)GA(N-Me)IL (NFGAIL
      GI) and the 37-residue non-amyloidogenic hIAPP analog [(N-Me)G24, (N-Me)I26]-IAPP
      (IAPP-GI). For comparison, the effects of insulin, which is a natively occurring
      hIAPP aggregation inhibitor, rat IAPP (rIAPP), which is a natively non
      amyloidogenic hIAPP analog, and the hIAPP amyloid core peptide hIAPP(22-27) or
      NFGAIL were also studied. The aim of our study was to test whether and how the
      above peptides which have been shown to completely block or suppress hIAPP
      amyloidogenesis in bulk solution in vitro would also affect these processes in
      the presence of lipid membranes. To this end, attenuated total reflection Fourier
      transform infrared spectroscopy (ATR-FTIR) was applied. We find that IAPP-GI,
      NFGAIL-GI, insulin, and rIAPP are potent inhibitors of hIAPP fibrillization.
      Importantly, our data also suggest that the hetero-complexes of IAPP-GI, rIAPP,
      and insulin with hIAPP although non-amyloidogenic per se are still able to adsorb
      at the lipid membrane. By contrast, in the presence of NFGAIL-GI, interaction of
      hIAPP with the lipid membrane is completely abolished, consistent with NFGAIL-GI
      mediated sequestration of hIAPP via hetero-complexation in the aqueous phase
      mainly accounting for the observed strong effect of NFGAIL-GI on hIAPP
      fibrillogenesis at the lipid membrane interface. Finally, our studies show that
      once hIAPP is fibrillized at the water-lipid membrane interface with fibrils
      being attached to the lipid membrane, it cannot be disaggregated by all above
      peptides.

PMID- 20153101
TI  - Molecular basis for endotoxin neutralization by amphipathic peptides derived from
      the alpha-helical cationic core-region of NK-lysin.
AB  - An analysis of the interaction of the NK-lysin derived peptide NK-2 and of
      analogs thereof with bacterial lipopolysaccharide (LPS, endotoxin) was performed
      to determine the most important biophysical parameters for an effective LPS
      neutralization. We used microcalorimetry, FTIR spectroscopy, Zeta potential
      measurements, and small-angle X-ray scattering to analyze the peptide:LPS binding
      enthalpy, the accessible LPS surface charge, the fluidity of the LPS hydrocarbon
      chains, their phase transition enthalpy change, the aggregate structure of LPS,
      and how these parameters are modulated by the peptides. We conclude that (i) a
      high peptide:LPS binding affinity, which is facilitated by electrostatic and
      hydrophobic interactions and which leads to a positive Zeta potential, (ii) the
      formation of peptide-enriched domains, which destabilize the lipid packing,
      demonstrated by a drastic decrease of phase transition enthalpy change of LPS,
      and (iii) the multilamellarization of the LPS aggregate structure are crucial for
      an effective endotoxin neutralization by cationic peptides.

PMID- 20153102
TI  - Long-term survival and characterisation of human umbilical cord-derived
      mesenchymal stem cells on dermal equivalents.
AB  - During early embryogenesis, mesenchymal cells arise from the primitive epithelium
      and can revert to an epithelial phenotype by passing through mesenchymal-to
      epithelial transition (MET). Mesenchymal stem cells (MSC) of the Wharton's Jelly
      of the umbilical cord (UC-MSC) express pluripotency markers underlining their
      primitive developmental state. As mesenchymal stem cells from bone marrow (BM
      MSC) possess a strong propensity to ameliorate mesenchymal tissue damage, UC-MSC
      might also be able to differentiate into cells apart from the mesoderm, allowing
      replacement of ectodermal and mesodermal tissues. In this study, we analysed the
      possible epidermal differentiation of UC-MSC on dermal equivalents (DEs)
      consisting of collagen I/III with dermal fibroblasts and subjected to the culture
      conditions for tissue engineering of skin with keratinocytes. The culture
      conditions were further modified by pre-treating the cells with 5-azacytidine or
      by supplementing the medium with all trans retinoic acid. Interestingly, a
      subpopulation of UC-MSC (29%) co-expressed pan-cytokeratin (epithelial marker;
      pan-CK) and vimentin (mesenchymal marker) after isolation. Under the three
      dimensional conditions of skin, the number of pan-CK(+)-cells increased to >30%
      after 21 days of cultivation, while under osteogenic culture conditions the cells
      were pan-CK-negative, thus showing the influence of the artificial niche.
      Nevertheless, the pan-CK-expression was neither accompanied by typical epithelial
      morphology nor expression of other epidermal markers. The pan-CK-detection can be
      explained by the expression of cytokeratins in myofibroblasts. UC-MSC expressed
      alpha-smooth muscle actin after isolation and displayed all features of
      functional myofibroblasts like morphology, cell-mediated contraction of a
      collagen gel and production of components of the extracellular matrix (ECM). The
      treatment with all trans retinoic acid or 5-azacytidine could neither induce an
      epidermal differentiation nor enhance the myofibroblastic differentiation.
      Concluding, UC-MSC might be an interesting cell source to support the
      regeneration of wounds by their differentiation into myofibroblasts and their
      extensive synthesis of ECM components.

PMID- 20153103
TI  - Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human
      hepatocellular carcinoma cells and is effective via oral administration.
AB  - Cucurbitacin B is an anti-cancer drug candidate and its efficacy has been
      demonstrated in hepatocellular carcinoma (HCC). To explore its mechanism against
      HCC, BEL-7402 cells were treated with cucurbitacin B in vitro. Treatment with
      cucurbitacin B induced S phase arrest and apoptosis. The growth inhibition effect
      was associated with cyclin D1 and cdc-2 down regulations. Western blotting
      analysis of cell signaling molecules indicated that cucurbitacin B inhibited c
      Raf activation without affecting STAT3 phosphorylation. Moreover, in vivo study
      demonstrated that cucurbitacin B is effective against BEL-7402 xenograft when
      administrated orally.

PMID- 20153104
TI  - The establishment of a new mouse model with orthotopic esophageal cancer showing
      the esophageal stricture.
AB  - We established a promising new experimental animal model with an orthotopic
      xenograft of esophageal cancer that successfully represents poor oral intake, a
      major clinical feature of esophageal cancer. The advantage of this model is that
      no surgical technique is required, only the injection of a cell suspension by a
      needle and syringe via the esophageal lumen from the mouth, which provides a high
      reproducibility of tumor implantation and a rapid progress of outcome. We propose
      that this model is useful to study cancer-related outcomes and for developing new
      therapies for esophageal cancer, and we expect it to make a contribution to
      clinical practice.

PMID- 20153105
TI  - Adsorption and desorption behavior of herbicide diuron on various Chinese
      cultivated soils.
AB  - The adsorption-desorption behaviors of diuron were investigated in six cultivated
      soils of China. The effect of system pH and temperature were also studied. The
      data fitted the Freundlich equation very well. The adsorption K(F) values
      indicated the adsorption of diuron in the six soils was in the sequence of black
      soil (D)>yellow earth (F)>paddy soil (B)>yellow-brown soil (C)>yellow-cinnamon
      soil (A)>lateritic red earth (E). The adsorption K(F) and Freundlich exponents n
      were decreased when temperature was increased from 298 K to 318 K. However, the
      Gibb's free energy values were found less negative with the increasing
      temperature. Meanwhile, the extent of diuron adsorption on soil was at rather
      high level under low pH value conditions and decreased with increasing pH value.
      In addition, the desorption behavior of diuron in the six soils was in the
      sequence of lateritic red earth (E)>yellow-cinnamon soil (A)>paddy soil
      (B)>yellow earth (F)>yellow-brown soil (C)>black soil (D). At the same time,
      desorption hysteresis of diuron were observed in all of the tested soils. And the
      soil organic matter content may play an important role in the adsorption
      desorption behavior.

PMID- 20153106
TI  - Adsorption of methyl tertiary butyl ether on granular zeolites: Batch and column
      studies.
AB  - Methyl tertiary butyl ether (MTBE) has been shown to be readily removed from
      water with powdered zeolites, but the passage of water through fixed-beds of very
      small powdered zeolites produces high friction losses not encountered in flow
      through larger sized granular materials. In this study, equilibrium and kinetic
      adsorption of MTBE onto granular zeolites, a coconut shell granular activated
      carbon (CS-1240), and a commercial carbon adsorbent (CCA) sample was evaluated.
      In addition, the effect of natural organic matter (NOM) on MTBE adsorption was
      evaluated. Batch adsorption experiments determined that ZSM-5 was the most
      effective granular zeolite for MTBE adsorption. Further equilibrium and kinetic
      experiments verified that granular ZSM-5 is superior to CS-1240 and CCA in
      removing MTBE from water. No competitive adsorption effects between NOM and MTBE
      were observed for adsorption to granular ZSM-5 or CS-1240, however there was
      competition between NOM and MTBE for adsorption onto the CCA granules. Fixed-bed
      adsorption experiments for longer run times were performed using granular ZSM-5.
      The bed depth service time model (BDST) was used to analyze the breakthrough
      data.

PMID- 20153107
TI  - Environmentally friendly wood preservatives formulated with enzymatic-hydrolyzed
      okara, copper and/or boron salts.
AB  - Novel biocides, such as copper azole (CuAz) and ammoniacal copper quaternary
      (ACQ), are extensively used as substitutes for chromate copper arsenate (CCA) in
      wood preservation. However, the expense of these biocides has necessitated the
      development of cost-effective and environmentally friendly wood preservatives.
      This study was conducted to investigate the effectiveness against decaying fungi
      of the preservatives formulated with enzymatic-hydrolyzed okara (OK), which is an
      organic waste produced from the manufacture of tofu, CuCl(2) (CC) and/or
      Na(2)B(4)O(7).10H(2)O (B). With the addition of NH(4)OH as a dissociating agent,
      the addition of OK facilitated the target retention of most of the OK/CC and
      OK/CC/B preservative formulations in wood blocks. The OK-based wood preservatives
      (OK-WPs) were stable against hot-water leaching. When compared with control and
      CC-treated wood blocks, the leached wood blocks treated with OK/CC and OK/CC/B
      formulations showed excellent decay resistance against both Postia placenta and
      Gloeophyllum trabeum, especially when OK was hydrolyzed by Celluclast at a
      loading level of 0.1 ml/g. Scanning electron microscopy (SEM) and SEM-energy
      dispersive X-ray (SEM-EDX) spectrometry analyses demonstrated that preservative
      complexes, such as OK-CC and OK-CC-B, existed in the wood blocks treated with
      OK/CC and OK/CC/B formulations. This study results support the potential
      application of OK-WPs as environmentally friendly wood preservatives capable of
      replacing CuAz and ACQ.

PMID- 20153108
TI  - The evaporative drying of sludge by immersion in hot oil: Effects of oil type and
      temperature.
AB  - We investigated the evaporative drying by immersion in hot oil (EDIHO) method for
      drying sludge. This involved heating oil to a temperature higher than that needed
      for moisture to be evaporated from the sludge by turbulent heat and mass
      transfer. We fry-dried sewage and leather plant sludge for 10 min in each of four
      different oils (waste engine, waste cooking, refined waste, and B-C heavy) and
      three different temperatures (140 degrees C, 150 degrees C, and 160 degrees C).
      Drying efficiency was found to be greater for higher temperatures. However,
      giving consideration to energy efficiency we suggest that the optimal temperature
      for fry-drying sludge is 150 degrees C. At 150 degrees C, the water content of
      sewage sludge reduced from 78.9% to between 1.5% (with waste cooking oil) and
      3.8% (with waste engine oil). The reduction in water content for leather plant
      sludge fry-dried at 150 degrees C was from 81.6% to between 1% (with waste
      cooking oil) and 6.5% (with refined waste oil). The duration of the constant rate
      drying period was also influenced by the type of oil used: refined waste
      oil>waste engine oil>B-C heavy oil>waste cooking oil. The duration at 150 degrees
      C with waste cooking oil was 3 min for sewage sludge and 2 min for leather plant
      sludge. It is likely that the drying characteristics of oil are influenced by its
      thermal properties, including its specific heat, and molecular weight.

PMID- 20153109
TI  - Kinetics and thermodynamics of adsorption of ionizable aromatic compounds from
      aqueous solutions by as-prepared and oxidized multiwalled carbon nanotubes.
AB  - The adsorption of 1-naphthylamine, 1-naphthol and phenol on as-prepared and
      oxidized multiwalled carbon nanotubes (MWCNTs) has been investigated. The results
      illustrated that both as-prepared and oxidized MWCNTs showed high adsorption
      capacity for the three ionizable aromatic compounds (IACs) studied. Oxidation of
      MWCNTs increased the surface area and the pore volume, and introduced oxygen
      containing functional groups to the surfaces of MWCNTs, which depressed the
      adsorption of IACs on MWCNTs. Both Langmuir and Freundlich models described the
      adsorption isotherms very well and the adsorption thermodynamic parameters
      (DeltaG degrees, DeltaH degrees and DeltaS degrees) were measured. The adsorption
      for 1-naphthylamine, 1-naphthol and phenol is general spontaneous and
      thermodynamically favorable. The adsorption of phenol is an exothermic process,
      whereas the adsorption of 1-naphthylamine and 1-naphthol is an endothermic
      process. Results of this work are of great significance for the environmental
      application of MWCNTs for the removal of IACs from large volume of aqueous
      solutions.

PMID- 20153110
TI  - Degradation of carbofuran in aqueous solution by ultrasound and Fenton processes:
      Effect of system parameters and kinetic study.
AB  - To establish an efficient oxidation process for carbofuran degradation, the
      effects of some operating parameters such as dosages of H(2)O(2), Fe(2+) and
      initial carbofuran concentrations were observed during carbofuran degradation by
      the ultrasound process, Fenton process and a combined ultrasound/Fenton process.
      The degradation kinetics of carbofuran was also examined based on the
      experimental data. The results show that more than 99% of the carbofuran was
      degraded by the ultrasound/Fenton process within short reaction time periods.
      Increased dosages of H(2)O(2) and Fe(2+) enhanced the degradation of carbofuran
      in the ultrasound and Fenton oxidation processes, but initial carbofuran
      concentrations decreased carbofuran degradation in both the Fenton and
      ultrasound/Fenton processes. The degradation kinetics of carbofuran by the three
      oxidation processes was found to be in accordance with first-order reaction
      kinetics. The results provide fundamental information about the treatment of
      carbofuran wastewater and/or other pesticides by the ultrasound/Fenton oxidation
      process.

PMID- 20153111
TI  - Adsorption of copper(II) on multiwalled carbon nanotubes in the absence and
      presence of humic or fulvic acids.
AB  - The adsorption of Cu(II) on multiwalled carbon nanotubes (MWCNTs) as a function
      of pH and ionic strength in the absence and presence of humic acid (HA) or fulvic
      acid (FA) was studied using batch technique. The results indicated that the
      adsorption is strongly dependent on pH but independent of ionic strength. A
      positive effect of HA/FA on Cu(II) adsorption was found at pH <7.5, whereas a
      negative effect was observed at pH >7.5. The adsorption isotherms can be
      described better by the Freundlich model than by the Langmuir model in the
      absence and presence of HA/FA. Adsorption isotherms of Cu(II) at higher initial
      HA/FA concentrations are higher than those of Cu(II) at lower FA/HA
      concentrations. The thermodynamic data calculated from temperature-dependent
      adsorption isotherms suggested that the adsorption was spontaneous and enhanced
      at higher temperature. Results of this work suggest that MWCNTs may be a
      promising candidate for the removal of heavy metal ions from aqueous solutions.

PMID- 20153112
TI  - Regeneration of carbon nanotubes exhausted with dye reactive red 3BS using
      microwave irradiation.
AB  - Carbon nanotubes (CNTs) exhausted with dye reactive red 3BS were regenerated by
      microwave irradiation under N(2) atmosphere. High regeneration efficiency was
      achieved and the regeneration efficiency reached 92.8% after four cycles
      regeneration. The decrease in adsorption capacity was suggested to be due to the
      deposition of decomposition residues in CNT pores, which blocked the carbon
      porosity and decreased the specific surface area.

PMID- 20153113
TI  - Establishing aerosol exposure predictive models based on vibration measurements.
AB  - This paper establishes particulate exposure predictive models based on vibration
      measurements under various concrete drilling conditions. The whole study was
      conducted in an exposure chamber using a full-scale mockup of concrete drilling
      simulator to simulate six drilling conditions. For each drilling condition, the
      vibration of the three orthogonal axes (i.e., a(x), a(y), and a(z)) was measured
      from the hand tool. Particulate exposure concentrations to the total suspended
      particulate (C(TSP)), PM(10) (C(PM10)), and PM(2.5) (C(PM2.5)) were measured at
      the downwind side of the drilling simulator. Empirical models for predicting
      C(TSP), C(PM10) and C(PM2.5) were done based on measured a(x), a(y), and a(z)
      using the generalized additive model. Good agreement between measured aerosol
      exposures and vibrations was found with R(2)>0.969. Our results also suggest that
      a(x) was mainly contributed by the abrasive wear. On the other hand, a(y) and
      a(z) were mainly contributed by both the impact wear and brittle fracture wear.
      The approach developed from the present study has the potential to provide a
      cheaper and convenient method for assessing aerosol exposures from various
      emission sources, particularly when conducting conventional personal aerosol
      samplings are not possible in the filed.

PMID- 20153115
TI  - Spatial niche competition among helminth parasites in horse's large intestine.
AB  - The spatial distribution of large intestinal helminth parasites of 50 horses was
      studied. Both adult and mucosal larval stages were examined and counted within
      the ventral colon, dorsal colon and caecum. Thirty-three species of adult
      parasites were identified and their distribution in the three large intestinal
      regions reported, together with the localization of cyathostome encysted larvae
      and of empty mucosal cysts. In order to highlight interspecific interactions,
      both Spearman pairwise correlation (among all parasites) and multivariable
      negative binomial regression (among the most abundant parasites) were performed.
      Interactions among parasite species are very important from the ecological and
      parasitological point of view as they can modulate the abundance and the spatial
      distribution of parasites, as well as the composition of the infracommunity. The
      main results were: the selection of preferred sites of horse's large intestinal
      helminths has been confirmed; all statistically significant pairwise correlation
      coefficients (359 out of 666) were positive; the build up of multivariable
      regression models brought to light both negative and positive interactions; the
      most interesting competitive interactions have been observed between the most
      abundant and relatively large strongyle species: Strongylus edentatus and
      Strongylus vulgaris in the caecum and ventral colon. When S. edentatus is in the
      caecum, the favourite site of S. vulgaris, the latter decreases especially in the
      caecum. On the other hand, when S. edentatus is in the ventral colon, its
      favourite site, there is no negative relationship with S. vulgaris in the ventral
      colon and the positive correlation observed with bivariate analysis is
      maintained. The common belief that the horse large intestinal parasite community
      is isolationist, due to the absence of negative pairwise interaction, is
      therefore contradicted by the present study.

PMID- 20153116
TI  - Alighting and feeding behaviour of tabanid flies on horses, kangaroos and pigs.
AB  - Successful mechanical transmission of surra between animals by tabanid flies
      (Diptera: Tabanidae) depends to a large extent on the blood-feeding behaviour of
      the tabanid species prevalent in the area. We studied tabanid-host interactions
      in Australia to better predict risk of surra transmission and design intervention
      strategies. At least six tabanid species were observed alighting on horses, pigs
      and kangaroos, but the most abundant were Tabanus pallipennis Macquart,
      Pseudotabanus silvester Bergroth and T. townsvilli Ricardo. The behaviour of
      tabanids in terms of landing location on the host body, duration of feeding and
      the proportion completing the blood-meal varied with fly species and host
      species. The findings predict that some species of tabanid such as T. pallipennis
      should be better vectors and some species of host such as pigs should be better
      reservoirs of surra based on the inability of flies to feed to repletion and
      longer feeding durations. This will result in multiple feeds and increased risk
      of exposure to the infectious agent, respectively, which increases the risk of
      transmission. Insecticide treatments should target preferred feeding sites on the
      host's body.

PMID- 20153117
TI  - Usefulness of detection of specific IgM and IgG antibodies for diagnosis of
      clinical encephalitozoonosis in pet rabbits.
AB  - Encephalitozoon cuniculi is an obligate intracellular pathogen that has wide host
      distribution, but primary affects rabbits. This study presents a
      seroepidemiological study of E. cuniculi infection in 500 pet rabbits from the
      Czech Republic using ELISA capable of measuring IgM and IgG antibodies. Specific
      IgM antibodies, reflecting acute, reactivated infection or reinfection, were
      detected in 32.4% of all rabbits. IgG antibodies indicating chronic infection,
      were presented in 68.0% of all rabbits. The highest detection rate of IgM (54.4%)
      and IgG (86.1%) antibodies was ascertained in rabbits with neurological symptoms
      (n=79, group I). In rabbits with renal disorders (n=47, group II) 36.2% animals
      were specific IgM and 80.9% IgG positive. Out of 9 rabbits with ocular disorders
      (group III), 44.4% were positive for anti-E. cuniculi IgM and 77.8% for IgG
      antibodies. In rabbits with multiple signs (neurological and renal or ocular,
      n=16, group IV), 43.8% animals were specific IgM and 68.8% IgG positive. Out of
      287 rabbits with other disease (group V), 26.5% were positive for anti-E.
      cuniculi IgM and 64.1% for IgG antibodies. However, the high presence of IgM
      (24.2%) and IgG (51.6%) antibodies was detected in clinically healthy rabbits
      (n=62, group VI). Toxoplasma gondii infection should be considered as a
      differential diagnosis for neurological and ocular disorders in rabbits. Using
      ELISA, 19.2% from all rabbits were positive for specific anti-T. gondii IgG. The
      highest seropositivity was detected in group III (44.4%). Simultaneous testing of
      IgM and IgG specific antibodies give an indication of the infection status.
      Presence of IgM antibodies is indicative for active infection with requirement to
      institute proper antimicrosporidial therapy. As active infection was detected in
      considerably high numbers of rabbits with clinical signs that are not usually
      associated with E. cuniculi, and even in asymptomatic rabbits, detection of both
      isotypes of specific antibodies should be a routine part of a health check in
      rabbits.

PMID- 20153118
TI  - An autochthonous case of cutaneous bovine leishmaniasis in Switzerland.
AB  - The present case report describes a novel etiological agent of cutaneous
      leishmaniasis that appears for the first time in a cow. A similar agent had
      recently been described as causing autochthonous infections in horses of Germany
      and Switzerland. The infection in the cow was initially diagnosed upon clinical
      and immunohistological findings. Subsequent comparative sequence analysis of
      diagnostic PCR products from the internal transcribed spacer 1 (ITS1) of ssrRNA
      classified the respective isolate as neither Old World nor New World Leishmania
      species, but yielded complete identity of the analysed sequence with the above
      mentioned horse cases and 98% identity to Leishmania sp. siamensis, an organism
      recently identified in a visceral leishmaniasis patient from Thailand. The
      potential transmitting vectors for all these cases have not yet been identified.
      Future investigations will have to elucidate the veterinary-epidemiological
      relevance of this etiological agent, as well as biological parameters such as
      transmission mode and geographical origin and distribution.

PMID- 20153119
TI  - Trichinella infection in wild boars (Sus scrofa) from a protected area of
      Argentina and its relationship with the presence of humans.
AB  - In Argentina, Trichinella infection has been documented in humans and animals of
      several provinces since 1930. This zoonotic parasite infection has been recently
      detected in humans and pigs of a region historically considered as Trichinella
      free, suggesting the spread of these pathogens. The aim of the present work was
      to investigate the presence of Trichinella infection in wild boars (Sus scrofa)
      and in the human population living in a protected area. Trichinella infection has
      been investigated by serology (in humans and wild boars) and by artificial
      digestion of wild boar muscles. The isolated Trichinella larvae have been
      identified at the species level by multiplex PCR. A geographical information
      system has been used to collect environmental data. The results showed the
      circulation of Trichinella spiralis in wild boars with a low parasite burden, and
      suggest the influence of human behavior on the transmission. The transplacental
      passage of parasite is postulated. It follows that the declaration of region as
      Trichinella-free should be carefully established by means of extensive monitoring
      programs, not only in humans and domestic animals but also in wildlife.

PMID- 20153120
TI  - An evaluation of pain-related anxiety among daily cigarette smokers in terms of
      negative and positive reinforcement smoking outcome expectancies.
AB  - The present investigation sought to evaluate the unique explanatory relevance of
      pain-related anxiety in relation to negative and positive reinforcement smoking
      outcome expectancies among 135 (40.7% female; M(age) = 26.11, SD = 11.23) adult
      daily cigarette smokers. As predicted, pain-related anxiety was significantly
      related to greater expectancies that smoking will decrease negative affect, and
      lesser expectancies that smoking will result in positive outcomes. The observed
      effects were evident above and beyond the variance accounted for by gender,
      current level of non-specific bodily pain, daily cigarette use, relations with
      non-criterion outcome expectancies, and shared variance with anxiety sensitivity.
      Results suggest that there may be segments of the smoking population who are at
      relatively greater risk for certain expectancies for tobacco smoking by virtue of
      individual differences in pain-related anxiety.

PMID- 20153121
TI  - An investigation of relations between crystal methamphetamine use and
      posttraumatic stress disorder.
AB  - Evidence documents elevated rates of various types of drug use among people with
      posttraumatic stress disorder (PTSD). However, relatively little research has
      specifically examined crystal methamphetamine (CM) use among individuals with
      PTSD. The present study examined the relation between PTSD diagnostic status,
      PTSD symptom severity within symptom type clusters, and CM use histories among
      traumatic event-exposed individuals with versus without PTSD. Consistent with
      expectations, individuals with PTSD were significantly more likely to report CM
      use than trauma-exposed individuals without PTSD. Additionally, CM users with
      PTSD reported a longer duration of CM use than trauma-exposed CM users without
      PTSD. Finally, PTSD avoidance and hyperarousal symptoms, but not re-experiencing,
      were related to CM use. The potential clinical and research implications of the
      findings are discussed.

PMID- 20153122
TI  - Disturbed colonic motility contributes to anorectal symptoms and dysfunction
      after radiotherapy for carcinoma of the prostate.
AB  - PURPOSE: To evaluate the role of colonic motility in the pathogenesis of
      anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the
      prostate. PATIENTS AND METHODS: Thirty-eight patients, median age 71 (range, 50
      81) years with localized prostate carcinoma randomized to one of two radiation
      dose schedules underwent colonic transit scintigraphy and assessment of anorectal
      symptoms (questionnaire), anorectal function (manometry), and anal sphincteric
      morphology (endoanal ultrasound) before and at 1 month and 1 year after RT.
      RESULTS: Whole and distal colonic transit increased 1 month after RT, with faster
      distal colonic transit only persisting at 1 year. Frequency and urgency of
      defecation, fecal incontinence, and rectal bleeding increased 1 month after RT
      and persisted at 1 year. Basal anal pressures remained unchanged, but progressive
      reductions occurred in anal squeeze pressures and responses to increased intra
      abdominal pressure. Rectal compliance decreased progressively in the patients,
      although no changes in anorectal sensory function ensued. Radiotherapy had no
      effect on the morphology of the internal and external anal sphincters. Distal
      colonic retention was weakly related to rectal compliance at 1 month, but both
      faster colonic transit and reduced rectal compliance were more frequent with
      increased fecal urgency. At 1 year, a weak inverse relationship existed between
      colonic half-clearance time and frequency of defecation, although both faster
      whole-colonic transit and reduced rectal compliance occurred more often with
      increased stool frequency. CONCLUSION: Colonic dysmotility contributes to
      anorectal dysfunction after RT for carcinoma of the prostate. This has
      implications for improving the management of anorectal radiation sequelae.

PMID- 20153123
TI  - DNA repair alterations in children with pediatric malignancies: novel
      opportunities to identify patients at risk for high-grade toxicities.
AB  - PURPOSE: To evaluate, in a pilot study, the phosphorylated H2AX (gammaH2AX) foci
      approach for identifying patients with double-strand break (DSB) repair
      deficiencies, who may overreact to DNA-damaging cancer therapy. METHODS AND
      MATERIALS: The DSB repair capacity of children with solid cancers was analyzed
      compared with that of age-matched control children and correlated with treatment
      related normal-tissue responses (n = 47). Double-strand break repair was
      investigated by counting gammaH2AX foci in blood lymphocytes at defined time
      points after irradiation of blood samples. RESULTS: Whereas all healthy control
      children exhibited proficient DSB repair, 3 children with tumors revealed clearly
      impaired DSB repair capacities, and 2 of these repair-deficient children
      developed life-threatening or even lethal normal-tissue toxicities. The
      underlying mutations affecting regulatory factors involved in DNA repair pathways
      were identified. Moreover, significant differences in mean DSB repair capacity
      were observed between children with tumors and control children, suggesting that
      childhood cancer is based on genetic alterations affecting DSB repair function.
      CONCLUSIONS: Double-strand break repair alteration in children may predispose to
      cancer formation and may affect children's susceptibility to normal-tissue
      toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect
      DSB repair deficiencies and thus enables identification of children at risk for
      high-grade toxicities.

PMID- 20153124
TI  - T1N0 to T2N0 squamous cell carcinoma of the glottic larynx treated with
      definitive radiotherapy.
AB  - PURPOSE: To report the treatment outcomes of definitive radiotherapy (RT) for
      early-stage squamous cell carcinoma (SCCA) of the glottic larynx. METHODS AND
      MATERIALS: We retrospectively reviewed the medical records of 585 patients with
      T1N0 to T2N0 invasive SCCA of the glottic larynx treated between 1964 and 2006
      with RT alone. All patients had at least 2 years of follow-up, had histologic
      diagnosis of invasive SCCA, and received continuous-course RT. None of these
      patients received chemotherapy or had elective nodal RT. The probabilities of
      local control (LC), ultimate LC, ultimate LC with larynx preservation, neck
      control, cause-specific survival (CSS), and overall survival (OS) were calculated
      by the Kaplan-Meier product-limit method. RESULTS: The median follow-up for
      survivors was 12 years. Five-year LC rates were as follows: T1A, 94%; T1B, 93%;
      T2A, 80%; and T2B, 70%. Multivariate analysis revealed that overall treatment
      time greater than 41 days (p = 0.001) and poorly differentiated histology (p =
      0.016) adversely affected LC. Five-year rates of ultimate LC with laryngeal
      preservation were: T1A, 95%; T1B, 94%, T2A, 81%; and T2B, 74%. Twenty-four (4%)
      of 585 patients failed in the neck; only 7 neck failures (1%) were isolated. Five
      year CSS and OS rates were as follows: T1A, 97% and 82%; T1B, 99% and 83%; T2A,
      94% and 76%; and T2B, 90% and 78%, respectively. Ten (1.7%) patients had severe
      and/or fatal complications. One patient died of a radiation-induced carotid
      artery angiosarcoma. CONCLUSION: Based on our study results, RT cures a high
      proportion of patients with T1N0 to T2N0 glottic SCCAs and has a low rate of
      severe complications.

PMID- 20153125
TI  - [Operative delivery data in France for 2007: results of a national survey within
      teaching hospitals].
AB  - AIM: Clinical Practice Guidelines of the French College of Gynecologists and
      Obstetricians concerning operative deliveries were published in December 2008.
      That is why a national survey was performed for the year 2007 so as to obtain an
      inventory of obstetrical practices regarding the geographical distribution of the
      type of instrument used for operative deliveries following the level of each
      teaching hospital concerned. MATERIAL AND METHODS: We included in our study 49
      teaching hospitals from metropolitan France and the overseas departments and
      territories. For the year 2007, we noted the number of operative deliveries, the
      type of instrument used, as well as the level of the maternity concerned with its
      total number of patients, births, cesarean sections, vaginal deliveries, and
      episiotomies. RESULTS: We obtained data from all 49 centres. The mean number of
      deliveries per year was 2203 for level I teaching hospitals, 2060 for level II
      and 2720 for level III, respectively. The rate of operative delivery was quite
      different from one centre to the other, ranging from 5.3 to 34.1% of all births.
      Similarly, for the type of instrument used, there existed clear geographical
      disparities although the notion of "School's instrument" was not as preeminent as
      before since most centres used at least two instruments. Moreover, the rate of
      cesarean varied from 9 to 29.5% (all levels concerned) with a national mean rate
      of 20.7% for teaching hospitals. Finally, mean rate of episiotomies ranged from
      3.6 to 60%. DISCUSSION: This study showed that important differences existed
      between teaching hospitals in the use of instruments and that obstetrical
      practices are far from being uniform. However, in 2007, the routine use of more
      than one instrument in each centre was most usual, as opposed to the situation
      some decades ago. The use of obstetrical vacuum extractors has been largely
      disseminated. Each of the three types of instruments has specific indications and
      mastering at least two instruments seems more secure in the management of the
      numerous obstetrical situations. It is up to teaching hospitals to make sure that
      the use of at least two instruments is taught for operative deliveries. The
      recent publication of Clinical Practice Guidelines would probably help in
      standardizing operative deliveries in years to come.

PMID- 20153126
TI  - Perinatal nutrient restriction reduces nephron endowment increasing renal
      morbidity in adulthood: a review.
AB  - Perinatal malnutrition has been included among the causes of renal disease in
      adulthood. Here, we consider the relationships between early supply of specific
      nutrients (such as protein, fat, vitamins and electrolytes) and renal endowment.
      Prenatal and postnatal nutrition mismatch is also discussed. In addition, this
      article presents the role of nutrition of both mothers and pre-term infants on
      nephron endowment, with final practical considerations.

PMID- 20153127
TI  - Neurodevelopmental outcome after COX inhibitor treatment for patent ductus
      arteriosus.
AB  - AIM: To compare neurodevelopmental results in very low birth weight (VLBW)
      infants two years after successful or failed cyclooxygenase inhibitor treatment
      with either indomethacin or ibuprofen for a haemodynamically significant patent
      ductus arteriosus (hsPDA). METHODS: We retrospectively evaluated closure rates
      and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with
      indomethacin and 93 with ibuprofen. RESULTS: Indomethacin and ibuprofen therapy
      groups did not differ in their baseline clinical profile (median gestational age
      26.0 and 26.2wksd) in early (median CRIB 6 and 5, respiratory distress >2 degrees
      in 36 and 34 infants) and late morbidities (intraventricular hemorrhage >2
      degrees in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80
      and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome.
      The therapy failure group (54 infants) was characterized by lower median
      gestational age (25.0wksd) and higher mortality (17%). No differences were found
      in the neurodevelopmental outcome of the surviving infants with ligation as
      compared to the survivors with successful pharmacological closure of the PDA at
      24months corrected age. CONCLUSION: Use of either ibuprofen or indomethacin for
      closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW
      infants.

PMID- 20153128
TI  - Different pre-term formulas for different pre-term infants.
AB  - Optimal nutrition is one of the most important aspects in the care of pre-term
      infants, especially for the gestationally youngest ones. These infants should
      receive a supply of nutrients that can sustain growth similar to that of a third
      trimester normal foetus. Traditional pre-term formulas do not ensure an optimal
      protein supply except when fed at high volumes, with an excess of fat and
      carbohydrates. Formulas with a protein content of 2-2.5 g 100ml(-1) and a
      protein/energy (P:E) ratio of less than 3g 100 kcal(-1) are not the best choice
      for the very low birth weight (VLBW) infants. We have tested a new formulation
      designed for the nutrition of the VLBW infants that is characterised by a protein
      content of 2.9 g 100ml(-1) and a P:E ratio of 3.5 g 100 kcal(-1). The milk
      formula was well tolerated and associated with better weight gain compared with
      fortified breast milk (18.1 vs. 15.2 g kg(-1)day(-1); p=0.0015). These results
      were obtained with a noticeably lower fluid supply (157 vs. 177 ml kg day(-1);
      p<0.0001) and lower energy intake (130 vs. 151 kcal kg(-1)day(-1); p<0.0001).
      Infant length and head circumference did not differ significantly between groups.
      Currently, the use of a formula with a P:E ratio of 3.5 g 100 kcal(-1) appears to
      be safe and to represent the best choice available for the gestationally youngest
      infants.

PMID- 20153129
TI  - Modulating peripheral gonadotrophin levels affects follicular expression of mRNAs
      encoding insulin-like growth factor binding proteins in sheep.
AB  - Evidence suggests that the insulin-like growth factor binding proteins (IGFBPs)
      are involved in modulating the role that IGF-I and -II play in regulating
      follicular growth and development in sheep. However, little information exists as
      to the role that key peripheral factors play in regulating the expression of
      IGFBP components within the follicle. The present study investigated the
      regulatory effects of FSH and LH on gene expression for IGFBP-2 to -6 in ovine
      follicles, using bovine follicular fluid (bFF) and gonadotrophin-releasing
      hormone antagonist (GnRHa) model systems to perturb endogenous gonadotrophin
      secretion. Gene expression studies were carried out using in situ hybridisation
      with sheep-specific ribonucleotide probes. Treatment of ewes with bFF had few
      consistent effects on IGFBP-3 and -4 mRNA expression in follicles, whereas bFF
      treatment resulted in significant decreases in IGFBP-2 and IGFBP-6 mRNA
      expression in only medium follicles 60 h after onset of bFF, and in follicles 12h
      after the onset of bFF, respectively. Treatment of ewes with GnRHa resulted in
      transient significantly increased IGFBP-2 mRNA in healthy follicles in comparison
      to early atretic or atretic follicles 12h post-GnRHa (P<0.05), in IGFBP-3 mRNA in
      early atretic and atretic follicles 36 h post-GnRHa (P<0.001), and IGFBP-5 mRNA
      in follicles 12h post-GnRHa (P<0.001). In contrast, GnRHa treatment resulted in
      significant decreases in IGFBP-4 (P<0.001) and IGFBP-6 (P<0.01) mRNA expression
      in large follicles 36 h post-GnRHa, and atretic follicles by 60 h post-GnRHa,
      respectively. These data highlight that FSH and LH are involved, at least in
      part, in mediating the proliferative and differentiative changes in
      intrafollicular IGFBP levels that are observed during follicular growth and
      atresia in the sheep.

PMID- 20153130
TI  - Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography
      tandem mass spectrometry.
AB  - An ion-pair reversed phase liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method has been developed for the quantification of a phosphorothioate
      oligonucleotide (PS-OGN) PF-ODN and its metabolites 5'N-1/3'N-1, 5'N-2 and 5'N-3
      in rat plasma. Plasma samples were prepared with an initial
      phenol/dichloromethane liquid-liquid extraction followed by a solid phase
      extraction. Chromatographic separation was performed with a gradient system on a
      Phenomenex Gemini C(18) column using hexafluoro-2-propanol/triethylamine buffer
      and methanol as the mobile phase at a flow rate of 0.5mL/min. Except for 5'N-1
      and 3'N-1, which were coeluted and could not be differentiated by mass
      spectrometer, the other analytes were separated chromatographically and mass
      spectrometrically. The detection was carried out in multiple reaction monitoring
      (MRM) mode using a negative electrospray ionization (ESI) interface. The lower
      limit of quantification (LLOQ) achieved was 4.0ng/mL for PF-ODN and its four
      metabolites with acceptable precision and accuracy. Inter-day and intra-day RSD
      for three quality control (QC) levels across validation runs were less than 12.0%
      and the accuracy ranged from -9.6% to 6.0% for the analytes. This validated LC
      MS/MS method was applied to a preliminary pharmacokinetic study of PF-ODN in
      rats.

PMID- 20153131
TI  - Fulminant myocarditis associated with pandemic H1N1 influenza A virus in
      children.

PMID- 20153132
TI  - Heart failure patients with a lower educational level and better cognitive status
      benefit most from a self-management group programme.
AB  - OBJECTIVE: The Chronic Disease Self-Management Programme (CDSMP)was recently
      evaluated among patients with congestive heart failure (CHF) in a randomized
      controlled trial (n = 317) with twelve months of follow-up after the start of the
      programme. That trial demonstrated short-term improvements in cardiac-specific
      quality of life. The current study assessed which of the patients participating
      in this trial benefited most from the CDSMP with respect to cardiac-specific
      quality of life. METHODS: Subgroup analyses were conducted using mixed-effects
      linear regression models to assess the relationship between patient
      characteristics and the effects of the CDSMP on cardiac-specific quality of life.
      RESULTS: In the short term, patients with better cognitive status benefited more
      from the CDSMP than their poorer functioning counterparts. In addition, lower
      educated patients benefited more from the CDSMP than their higher educated
      counterparts during total follow-up. CONCLUSION: Subgroup effects were found for
      cognitive status and educational level. Future research should be performed to
      validate current findings and further explore the conditions under which CHF
      patients may benefit more from the programme. PRACTICE IMPLICATIONS: These
      results indicate that lower educated patients, in particular, should be
      encouraged to participate in the CDSMP. In addition, healthcare practitioners are
      recommended to take into account potential cognitive impairments of patients.

PMID- 20153133
TI  - Healthfulness of the U.S. food supply: little improvement despite decades of
      dietary guidance.
AB  - BACKGROUND: Every 5 years for the past several decades, the USDHHS and the U.S.
      Department of Agriculture have issued and updated the Dietary Guidelines for
      Americans, which form the basis of federal nutrition policy and have shown
      remarkable consistency across various editions among the major themes. PURPOSE:
      This paper examines whether the U.S. food supply is sufficiently balanced to
      provide the recommended proportions of various foods and nutrients per the amount
      of energy, whether this balance has shifted over time, and which areas of the
      food supply may have changed more than others. METHODS: The Healthy Eating Index
      2005 (HEI-2005) was used to measure the dietary quality of the U.S. food supply,
      from 1970 to 2007. Sources of data were the USDA's food availability data, loss
      adjusted food availability data, and nutrient availability data, and the U.S.
      Salt Institute's data on salt sold for human consumption. RESULTS: Total HEI-2005
      scores improved by about 10 points between 1970 and 2007, but they never achieved
      even 60 points on a scale from 0 to 100. Although meats and total grains were
      supplied generally in recommended proportions, total vegetables, total fruit,
      whole fruit, and milk were supplied in suboptimal proportions that changed very
      little over time. Saturated fat, sodium, and calories from solid fat, alcoholic
      beverages, and added sugars were supplied in varying degrees of unhealthy
      abundance over the years. Supplies of dark-green/orange vegetables and legumes
      and whole grains were entirely insufficient relative to recommendations, with
      virtually no change over time. CONCLUSIONS: Deliberate efforts on the part of
      policymakers, the agriculture sector, and the food industry are necessary to
      provide a supply of foods consistent with nutrition recommendations and to make
      healthy choices available to all.

PMID- 20153134
TI  - [A case study of occupational rhizarthrosis among octopus fishermen in the
      Mediterranean Sea].

PMID- 20153135
TI  - [Elderly people, precariousness, social handicap and length of stay: pilot study
      at the Lariboisiere-Fernand Widal Hospital Group in Paris].
AB  - OBJECTIVES: To administer a social handicap questionnaire associated with French
      DRGs (PMSI) to determine the social handicaps of a population hospitalized in a
      public health establishment and to measure the cost implications for the
      establishment due to increased length of stay (DMS). METHOD: A prospective pilot
      study has been carried out in the Lariboisiere-Fernand Widal Hospital Group in
      Paris targeting users 50 or more years old hospitalized for short stays in
      medicine, surgery and obstetrics. Data of the PMSI and answers to the
      questionnaire for hospitalisations longer than 24 hours have been exploited.
      RESULTS: Two hundred twenty-two stays from 8 to 23 November 2005 have been
      analyzed: 140 pertained to patients aged 50-69 years (27.8%) and 82 to patients
      aged 70 or more years (16.3%). Three-fourths of the persons aged 50-69 and 70 or
      over presented a social handicap: 45% showed a strong handicap and a third an
      average handicap. The three indicators "renter/owner", "interior comfort" and
      "family relations" were the major determinants of social handicap for those aged
      70 or more, 50-69 and 50 or more years. For the patients 70 years and over and
      those 50-69 years, with an average handicap, the indicator was "income" with the
      domain "patrimony." For strong handicaps, it was the indicator "scolarisation"
      for the 70 or more years and the indicator "income" for the 50-69 years old. When
      all classes and populations were pooled, the DMS was significantly lower than
      that of the ENC (p<0.001 for the 70 years and over; p<0.05 for the 50-69 years).
      With again all classes and populations pooled, patients 70 and over stayed in
      hospital 6.50 days less on average compared to data published by the ENC; those
      50-69 years stayed 3.57 days less. Persons aged 50 and over with a social
      handicap remained hospitalized on average more than 2.5 days: 2.2 days for the 70
      and over and 3.1 days for the 50-69 years group. In terms of hospital days that
      produces an increase of 18%, corresponding to a supplementary expenditure
      attributable to social handicap of approximately 5.9 million euros. CONCLUSION:
      This pilot study with a questionnaire disability social PMSI proposing specific
      aid, but also reducing the DMS, provides several promising information but also
      indicates the limits of our approach. Among these, we note in particular: (a) its
      regular feasibility requires constant supervision, wider and well-trained, (b)
      that the measurement of our tool can only be affirmed after its use in many
      patients, and (c) the classification of disability in social class could even be
      discussed again. We still wanted to explore whether through this initiative
      without much logistical, markers of interest had emerged, which seems to be the
      case.

PMID- 20153136
TI  - Management of treatment-related intermittent partial small bowel obstruction: the
      use of octreotide.

PMID- 20153137
TI  - Cultural factors affecting the differential performance of Israeli and
      Palestinian children on the Loewenstein Occupational Therapy Cognitive
      Assessment.
AB  - Cognitive performance is essential for children's functioning and may also
      predict school readiness. The suitability of Western standardized assessments for
      cognitive performance among children from different cultures needs to be
      elaborated. This study referred to the existence of differences in cognitive
      performance between and within children from the middle-east-Israeli and
      Palestinian on the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA),
      by elucidating cultural effects on the construct validity of the LOTCA using
      factor analysis. Participants included 101 Israeli and 125 Palestinian children
      from kindergarten, first and second grade who underwent the LOTCA. Factor
      analysis revealed four factors underlying items on the LOTCA, explaining the
      differences found between Israeli and Palestinian children in most of LOTCA
      subtests. Culture may affect the construct validity of the LOTCA and may explain
      the difference in performance between both cultural groups. LOTCA's validity as
      well as the validity of other instruments on which norms and decisions regarding
      the child's development and performance are made should be further evaluated
      among children from different cultural backgrounds.

PMID- 20153138
TI  - Percutaneous closure of a mitral perivalvular leak using three dimensional real
      time and color flow imaging.
AB  - The role of echocardiography, including three-dimensional (3D) echocardiography,
      during interventional procedures in the cardiac catheterization laboratory is
      continuing to expand as interventional cardiologists perform more catheter-based
      interventions. Echocardiography often complements angiographic imaging of cardiac
      structures and sometimes provides additional information not available by
      angiography and fluoroscopy. The closure of perivalvular leaks using catheter
      based techniques is one of the areas in which 3D echocardiography can be helpful.
      This case report describes the use of 3D real-time and color flow imaging during
      the closure of a mitral perivalvular leak. Three-dimensional echocardiography was
      used to assess the leak prior to intervention and the success of the intervention
      at the completion of the case.

PMID- 20153139
TI  - Functional magnetic resonance imaging of choice reaction time in chronic
      schizophrenia and first-degree relatives.

PMID- 20153140
TI  - Cognitive decline in schizophrenia from childhood to midlife: a 33-year
      longitudinal birth cohort study.
AB  - BACKGROUND: We examined cognitive deficits before and after onset of
      schizophrenia in a longitudinal study that: 1) covers a long time interval; 2)
      minimizes test unreliability by including the identical measure at both childhood
      and post-onset cognitive assessments; and 3) minimizes bias by utilizing a
      population-based sample in which participants were selected neither for signs of
      illness in childhood nor for being at risk for schizophrenia. METHODS:
      Participants in the present study, Developmental Insult and Brain Anomaly in
      Schizophrenia (DIBS), were ascertained from an earlier epidemiologic study
      conducted in Oakland, CA. The original version of the Peabody Picture Vocabulary
      Test (PPVT), a test of receptive vocabulary, was administered at age 5 or 9 and
      repeated as part of the DIBS study at an average age of 40. There were 10 DIBS
      cases with DSM-IV schizophrenia or schizoaffective disorder and 15
      demographically similar DIBS controls with both child and adult PPVT scores.
      RESULTS: Cases scored significantly lower than controls in childhood (d=0.95) and
      adulthood (d=1.67). Residualized scores indicating the number of SDs above or
      below one's predicted adult score revealed a mean case-control difference of 
      1.51SDs, consistent with significant relative decline over time among the cases
      (p<0.0013). CONCLUSIONS: In this prospective study, individuals who developed
      adult schizophrenia manifested impaired receptive vocabulary during childhood and
      further relative deterioration (or lack of expected improvement) between
      childhood and midlife. Limitations should also be acknowledged, including the
      small sample size and the fact that we cannot be certain when the continued
      deterioration took place.

PMID- 20153141
TI  - Genetic association study of KREMEN1 and DKK1 and schizophrenia in a Japanese
      population.
AB  - The aim of the current study was to examine the association of KREMEN1 and DKK1,
      two wnt pathway-related genes with schizophrenia in Japanese subjects. We
      genotyped 16 common genetic variants within the aforementioned genes and examined
      their associations with schizophrenia. Results demonstrated that a common variant
      in the promoter region of KREMEN1 might modulate the risk of schizophrenia in the
      Japanese. However, further replication will be needed for conclusive
      interpretation of the effect of this locus on the pathogenesis of schizophrenia.

PMID- 20153143
TI  - Medial prefrontal cortex hyperactivation during social exclusion in borderline
      personality disorder.
AB  - Frontal systems dysfunction and abandonment fears represent central features of
      borderline personality disorder (BPD). BPD subjects (n=10) and matched non
      psychiatric comparison subjects (n=10) completed a social-cognitive task with two
      confederates instructed to either include or exclude subjects from a
      circumscribed interaction. Evoked cerebral blood oxygenation in frontal cortex
      was measured using 16-channel functional near infrared spectroscopy. BPD subjects
      showed left medial prefrontal cortex hyperactivation during social exclusion
      suggesting potential dysfunction of frontolimbic circuitry.

PMID- 20153142
TI  - Working memory fMRI activation in cocaine-dependent subjects: association with
      treatment response.
AB  - Functional magnetic resonance imaging (fMRI) studies of early abstinence cocaine
      users offer information about the state of the brain when most cocaine users seek
      treatment. This study examined the relationship between pretreatment brain
      function and subsequent treatment response in 19 treatment-seeking early
      abstinence cocaine-dependent (CD) subjects. These subjects and 14 non-drug-using
      control subjects underwent fMRI while performing a working memory task with three
      levels of difficulty. CD subjects were then randomized to treatment studies.
      Results showed CD subjects had significantly lower (random effects, corrected for
      multiple comparisons) brain activation in caudate, putamen, cingulate gyrus,
      middle and superior frontal gyri, inferior frontal gyrus pars triangularis and
      pars opercularis, precentral gyrus, and thalamus compared with non-drug-using
      controls. Within CD subjects, thalamic activation significantly correlated with
      treatment response. This study shows CD subjects in early abstinence have
      alterations of brain function in frontal, striatal, and thalamic brain regions
      known to be part of a circuit associated with motor control, reward, and
      cognition. Subjects with pretreatment thalamic deactivation showed the poorest
      treatment response, possibly related to thalamic involvement in mesocortical and
      mesolimbic dopamine projections.

PMID- 20153144
TI  - Altered emotional information processing in borderline personality disorder: an
      electrophysiological study.
AB  - Emotional dysregulation is one of the key symptoms of patients with borderline
      personality disorder (BPD). In the present study it is hypothesized that
      borderline patients display a cortical hyper-responsivity to emotional stimuli
      compared with a healthy control group. Further, we aimed to examine whether BPD
      patients were able to suppress stimuli with negative emotional valence as well as
      healthy control participants could. This is the first study addressing the
      electrophysiological processing of emotional stimuli in BPD. The
      electrophysiological response to emotional information was studied among 30 BPD
      patients and compared with the response in 30 normal controls using event-related
      potentials (ERPs). Participants were shown pictures selected from the
      International Affective Picture System with neutral, positive, and negative
      valence. After performing an attentional task, the participants were asked to
      perform a reappraisal task. The assignment was to consciously suppress emotions
      that might occur after viewing pictures with an unpleasant content. Borderline
      patients displayed larger late positive potentials (LPP) to pictures with an
      unpleasant valence as compared with the control group, indicating an enhanced
      elaborative processing of unpleasant stimuli. However, they did not differ on the
      reappraisal task. Borderline patients show an enhanced emotional cortical
      reactivity to unpleasant stimuli as compared with a control group. This suggests
      an emotional dysfunctioning in BPD patients. This feature might be an important
      focus in the treatment of BPD.

PMID- 20153145
TI  - Voxel-based morphometry comparison between first episodes of psychosis with and
      without evolution to schizophrenia.
AB  - First episodes (FE) of psychosis may evolve or not to schizophrenia in ensuing
      years, but there is a lack of reliable predictors of which patients will have to
      face such an unfavorable outcome. Given the replicated structural alterations of
      the brain in schizophrenia, it seems advisable to assess whether the alterations
      of this kind that can be detected at the time of an initial psychotic episode are
      different depending on the outcome of the patients. To this end, here we applied
      voxel-based morphometry to assess whether the degree of cerebral abnormalities
      differ between 30 FE patients who evolved to schizophrenia in the ensuing 2years
      and another 14 FE patients who could not be diagnosed as such during that period.
      Forty-one controls were also included in the study. We found that the FE patients
      who evolved to schizophrenia had a significantly lower GM value than the controls
      bilaterally in the left dorsolateral prefrontal (BA 9) and in left anterior
      cingulate (BA 33) regions while the FE patients who did not develop schizophrenia
      showed a distinct, right-sided pattern of deviation (visual cortex, superior
      temporal gyrus and inferior frontal). The direct comparison between FE patients
      who evolved or not evolved to schizophrenia did not reveal significant
      differences. Taken together, our results support the notion that brain
      abnormalities may be different in psychotic FE patients depending on their
      evolution in the medium term.

PMID- 20153146
TI  - Manual validation of FreeSurfer's automated hippocampal segmentation in normal
      aging, mild cognitive impairment, and Alzheimer Disease subjects.
AB  - Hippocampal volume is reduced in Alzheimer Disease (AD) and has been proposed as
      a possible surrogate biomarker to aid early diagnosis. Whilst automated methods
      to segment the hippocampus from magnetic resonance images are available, manual
      segmentation, in spite of being time-consuming and unsuitable for large samples,
      is still the standard. In order to study the validity of FreeSurfer's automated
      method, we compared hippocampal automated measures with manual tracing in a
      sample composed of healthy elderly (N=41), Mild Cognitive Impairment (MCI)
      (N=23), and AD (N=25) subjects. Percent volume overlap, percent volume
      difference, correlations, and Bland-Altman plots were studied. Automated measures
      were slightly larger than hand tracing ones (mean difference 10%). Percent volume
      overlap showed good results, but was far from perfect (78%). Manual and automated
      volume correlations were approximately 0.84 and the Bland-Altman analysis showed
      acceptable interchangeability of methods. Within-group analysis demonstrated that
      patient samples obtained smaller values in validity indexes than controls.
      Globally, FreeSurfer's automated hippocampal volumetry showed adequate validity
      when compared to manual tracing, with a tendency to overestimation. Nevertheless,
      the greater difference between automated and manual segmentation in atrophic
      brains suggests that studies in AD based on this software could be more likely to
      produce false negatives.

PMID- 20153147
TI  - A time-saving and facilitating approach for segmentation of anatomically defined
      cortical regions: MRI volumetry.
AB  - In this study, we present an accurate, reliable, robust, and time-efficient
      technique for a semi-automatic segmentation of neuroanatomically defined cortical
      structures in Magnetic Resonance Imaging (MRI) scans. It involves manual drawing
      of the border of a region of interest (ROI), supported by three-dimensional (3D)
      visualization techniques (rendering), and a subsequent automatic tracing of the
      gray matter voxels inside the ROI by means of an automatic tissue classifier. The
      approach has been evaluated on a set of MRI scans of 75 participants selected
      from the Maastricht Aging Study (MAAS) and applied to cortical brain structures
      for both the left and right hemispheres, viz., the inferior prefrontal cortex
      (PFC); the orbital PFC; the dorsolateral PFC; the anterior cingulate cortex; and
      the posterior cingulate cortex. The use of a 3D surface-rendered brain can be
      rotated in any direction was invaluable in identifying anatomical landmarks on
      the basis of gyral and sulcal topography. This resulted in a high accuracy
      (anatomical correctness) and reliability: the intra-rater intra-class correlation
      coefficient (ICC) was between 0.96 and 0.99. Furthermore, the obtained time
      savings were substantial, i.e., up to a factor of 7.5 compared with fully manual
      segmentations.

PMID- 20153148
TI  - Short-TE proton magnetic resonance spectroscopy investigation in adolescents with
      attention-deficit hyperactivity disorder.
AB  - In this study, short echo time (1)H-magnetic resonance spectroscopy (MRS) was
      applied for quantification of neurometabolites using the LC Model algorithm in
      Taiwanese adolescents with attention-deficit hyperactivity disorder (ADHD).
      Proton magnetic resonance spectra were acquired bilaterally on the prefrontal
      area (part of the anterior cingulate gyrus and part of the medial frontal gyrus)
      in 15 adolescents with ADHD (average age of 13.88years) and 22 controls (average
      age of 14.85years). Absolute metabolite levels and ratios relative to creatine
      plus phosphocreatine (Cr+PCr) were obtained to be compared between groups.
      Results showed that adolescents with ADHD had significantly lower mean right
      prefrontal levels of Cr+PCr as compared with the controls. No significant
      differences between groups were noted in the remainder of the prefrontal
      metabolites. As for the group comparison of relative ratios, the N
      acetylaspartate/Cr+PCr ratio was significantly higher in the right prefrontal
      regions of ADHD adolescents. This finding provides evidence of a right prefrontal
      neurochemical alteration in ADHD adolescents, which is consistent with current
      ADHD theory of prefrontal neuropathology with developmental mechanism. In
      addition, it highlights the importance of the method in interpretation of MRS
      findings in the context of ADHD.

PMID- 20153149
TI  - High energy phosphate abnormalities normalize after antipsychotic treatment in
      schizophrenia: a longitudinal 31P MRS study of basal ganglia.
AB  - We reported increased high-energy phosphate metabolism in the basal ganglia of
      antipsychotic-naive schizophrenia patients using (31)P Magnetic Resonance
      Spectroscopy (MRS). These patients were followed up for 1 year and and reassessed
      using (31)P MRS. Fourteen (8 males) patients with DSM-IV schizophrenia and 14 (11
      males) healthy controls underwent (31)P MRS of sub-cortical structures
      (predominantly basal ganglia) twice (mean+/-S.D. interscan interval 1.15+/
      0.17year) on a 1.5T scanner. Total scores on the Positive and Negative Syndrome
      Scale (PANSS) decreased significantly after treatment in schizophrenia patients.
      Patients had significantly lower mean PCr/ATP ratios than healthy controls at
      baseline but not during the follow-up. In patients, there was a significant
      positive correlation between the magnitude of improvement in PANSS total scores
      and the extent of change in the PCr/ATP ratio. Findings support the hypothesis
      that reduction of energy demand or induction of decreased energy-demanding
      processes might underlie the mechanism of action of antipsychotics in
      schizophrenia.

PMID- 20153150
TI  - Brain activation during the perception of distorted body images in eating
      disorders.
AB  - Eating disorder (ED) patients have severe disturbances in the perception of body
      shape and weight. The authors investigated brain activation patterns during the
      perception of distorted body images in various subtypes of ED. Participants
      comprised 33 patients with EDs (11 with restricting-type anorexia nervosa (AN-R),
      11 with binging-purging type anorexia nervosa (AN-BP), 11 with bulimia nervosa
      (BN)) and 11 healthy women. Functional magnetic resonance imaging was used to
      examine cerebral response to morphed images of subjects' own bodies, as well as
      that of another woman. The amygdala was significantly activated in AN-R patients,
      AN-BP patients, and healthy women in response to their own fat-image, but this
      did not occur in BN patients. The prefrontal cortex (PFC) was significantly
      activated in AN-BP patients and healthy women, but not in AN-R and BN patients.
      Our results showed that the various EDs are different with respect to significant
      activation of the amygdala and PFC during the processing of participants' own fat
      image. Brain activation pattern differences between the various EDs may underlie
      cognitive differences with respect to distorted body image, and therefore might
      reflect a general failure to represent and evaluate one's own body in a realistic
      fashion.

PMID- 20153151
TI  - The association between the harm avoidance subscale of the Tridimensional
      Personality Questionnaire and serotonin transporter availability in the brainstem
      of male volunteers.
AB  - The relationship between harm avoidance scores of the Tridimensional Personality
      Questionnaire and serotonin transporter availability, as approximated using
      single photon emission computed tomography with [(123)I] ADAM, was examined. Our
      results showed a significant negative correlation between the harm avoidance
      total score, as well as the asthenia subscore, and serotonin transporter
      availability, particularly in males.

PMID- 20153152
TI  - Nanocharacterization and bactericidal performance of silver modified titania
      photocatalyst.
AB  - An environmental-friendly procedure for manufacturing silver (Ag) and titania
      (TiO(2)) nanocomposites in an aqueous solution is presented. This green synthetic
      approach results in the successful production of nanomaterials with high
      dispersion and crystallinity. The colloidal suspensions of the nanocomposites
      composed of metal and ceramic (Ag-TiO(2)) were found to be extremely stable over
      a prolonged time period. Morphologically, nanocomposites were found to be
      composed of near-spherical particles that were highly crystalline. The
      nanocomposites were mono-dispersed with particles varying in size from 20 to
      50nm, depending upon nanocomposite solution pH. Indexed metallic nanoscale silver
      exhibited a face-centered cubic (fcc) crystalline phase structure. Nanocomposite
      elemental composition studies indicated that the molar ratio of Ag and Ti was
      approximately 1-20. The binding energies and energy differences of Ag, Ti and O
      were well-indexed with their associated standard spectra. Nanocomposite optical
      absorption properties were consistent with noble metal nanoparticles. The
      zetapotential for the nanocomposites was higher at acidic pH and exhibited an
      absolute negative charge that apparently inhibited particle agglomeration.
      Escherichia coli (E. coli), a Gram-negative model microorganism was effectively
      inactivated using the nanocomposites under visible light at ambient temperature
      and pressure. The 'green chemistry' derived Ag-TiO(2) composites are applicable
      for the removal of biological impurities from drinking and underground water
      supplies. The results of the study indicated that nanocomposites could be
      specifically designed to prevent growth of bacteria in water.

PMID- 20153153
TI  - Modified tabu search approach for variable selection in quantitative structure
      activity relationship studies of toxicity of aromatic compounds.
AB  - OBJECTIVE: Variable selection is a key step in developing a successful
      quantitative structure-activity relationships (QSAR) analysis system. Tabu search
      (TS) can be used for variable selection which employs a flexible memory system to
      avoid convergence to local minima. But the convergence speed of TS depends on the
      initial solution and is slow. It usually reaches local minima since a single
      candidate solution is used to generate offspring. In the present paper, the TS
      algorithm was modified to assist TS to find the promising regions of the search
      space rapidly. METHODS AND MATERIALS: A version of modified TS algorithm is
      proposed to select variables in QSAR modeling and to predict toxicity of some
      aromatic compounds. In the modified TS, the information which shares mechanism
      among the best position of all iteration and the personal position is introduced
      in the step of generating neighbors of the given solution. The move function
      which directs the moving of the solution is recorded as tabu. The modified Cp
      statistic is employed as fitness function. RESULTS AND CONCLUSIONS: For
      comparison, the conventional TS and stepwise regression were also examined.
      Experimental results demonstrate that the modified TS is a useful tool for
      variable selection which converges quickly towards the optimal position.

PMID- 20153154
TI  - The treatment of hypercholesterolemic children: efficacy and safety of a
      combination of red yeast rice extract and policosanols.
AB  - BACKGROUND AND AIMS: The prevention of cardiovascular risk, as occurs in
      lipoprotein disorders, is required since childhood. Aim of the study was to
      evaluate, in a group of children affected by primary dyslipidemia, the efficacy,
      tolerability and safety of a short-term treatment with a dietary supplement
      containing red yeast rice extract and policosanols. METHODS AND RESULTS: 40
      children affected by heterozygous Familial Hypercholesterolemia (FH) (n=24) and
      Familial Combined Hyperlipidemia (FCH) (n=16), aged 8-16 years, were enrolled in
      a double-blind, randomized, placebo-controlled, cross-over trial. After a 4-week
      run-in period with only dietary advice, children received a dietary supplement
      containing 200mg red yeast rice extract, corresponding to 3mg of monacolins, and
      10mg policosanols once-daily and placebo for 8 weeks, separated by a 4-week
      washout period. Lipid profile was assessed after each treatment period. The
      dietary supplement, compared with the placebo, significantly reduced total
      cholesterol by 18.5% (p<0.001), LDL-C levels by 25.1% (p<0.001), and
      apolipoprotein B by 25.3% (p<0.001) when patients were considered as a whole
      group. Similar results were obtained when FH and FCH were considered separately
      and no significant difference between groups was detected. No significant
      differences were observed in HDL-C and apolipoprotein A-I levels. No adverse
      effects were detected when liver and muscular enzymes (AST, ALT, and CK) were
      determined. CONCLUSIONS: The treatment with a dietary supplement containing red
      yeast rice extract and policosanols has been for the first time successfully
      employed in hypercholesterolemic children. Results indicate this strategy as an
      effective, safe and well tolerated in a short-term trial.

PMID- 20153155
TI  - Antagonistic effects of two herbs in Zuojin Wan, a traditional Chinese medicine
      formula, on catecholamine secretion in bovine adrenal medullary cells.
AB  - In order to research the target of superior efficacy and lesser side effects,
      combination of herbal materials has been applied to phytotherapy for thousands of
      years in China and some other countries. Zuojin Wan (ZJW), a famous traditional
      Chinese medicine formula, is used in treating gastric diseases in China. It is
      composed of two herbs, Rhizoma Coptidis (RC) and Fructus Evodiae (FE) in the
      ratio of 6: 1(w/w). In the present study, we examined the effects of ZJW, RC, FE
      and active components isolated from these herbs on catecholamine (CA) secretion
      and intracellular calcium ([Ca(2+)](i)) in cultured bovine adrenal medullary
      cells. Extracts of ZJW and RC and berberine, palmatine and jatrorrhizine,
      components of RC, all inhibited CA secretion and rise in [Ca(2+)](i) induced by
      acetylcholine (ACh), veratridine (Ver) and/or 56 mM K(+). On the other hand,
      extract of FE, evodiamine and rutaecarpine, components of FE, stimulated CA
      secretion and rise in [Ca(2+)](i) induced by ACh. Furthermore, different
      proportions of RC and FE caused different responses in CA secretion. The present
      findings suggest that two herbs in ZJW have opposite effects, i.e., inhibitory
      effect of RC and stimulatory effect of FE, on CA secretion induced by
      acetylcholine in cultured bovine adrenal medullary cells.

PMID- 20153156
TI  - Processing and presentation of antigens derived from intracellular protozoan
      parasites.
AB  - Control of parasitic protozoan infections requires the generation of efficient
      innate and adaptive immune responses, and in most cases both CD8 and CD4 T cells
      are necessary for host survival. Since intracellular protozoa remodel the
      vacuolar compartments in which they reside, it is not obvious how their antigens
      enter the MHC class I and class II pathways. Studies using genetically engineered
      parasites have shown that host cell targeting, intracellular
      compartmentalization, subcellular localization of antigen within the parasite,
      and mechanism of invasion are important factors determining the presentation
      pathway utilized. The recent identification of endogenous parasite-derived CD8 T
      cell epitopes have helped confirm these concepts as well as provided new
      information on the processing pathways and the impact of parasite-stage specific
      antigen expression on the repertoire of responding T cells stimulated by
      infection. Elucidating the mechanisms governing antigen processing and
      presentation of intracellular protozoa may provide important insights needed for
      the rational design of effective vaccines.

PMID- 20153157
TI  - PSMB8 (LMP7) but not PSMB9 (LMP2) gene polymorphisms are associated to pigeon
      breeder's hypersensitivity pneumonitis.
AB  - Hypersensitivity Pneumonitis (HP) is a lung inflammatory disorder caused by
      inhalation of organic particles by a susceptible host. However, only a small
      proportion of individuals exposed to HP-associated antigens develop the disease,
      suggesting that additional host/environmental factors may play a role. We have
      previously found that genetic susceptibility associated to the major
      histocompatibility complex (MHC) plays an important role in this disease. The low
      molecular weight proteosome (LMP, currently named PSMB) genes code for subunits
      of the proteosome, a multimeric enzymatic complex that degrades proteins into
      peptides in order to be presented in the MHC class I pathway. We hypothesized
      that polymorphisms in PSMB8 or PSMB9 genes could be involved in the
      susceptibility to HP. Thus, in this study we analyzed the polymorphic site at
      amino acid position 60 (Arg/His) of the fourth exon in the PSMB9 gene and the
      amino acid position 49 (Gln/Lys) in the second exon of PSMB8 gene in 50 Mexican
      patients with HP and 50 healthy ethnically matched controls. PSMB typing was
      performed using polymerase chain reaction-restriction fragment length
      polymorphisms (PCR-RFLP). Our results demonstrated that HP patients had a
      significant increase of the PSMB8 KQ genotype frequency (OR = 7.25, CI = 2.61
      21.3; p = 0.000034). No differences were found in the distribution of PSMB9
      alleles/genotypes. However, PSMB9-RH/PSMB8 KQ haplotype was significantly
      increased in HP patients (OR = 6.77, CI = 1.34-65.31, p < 0.02). These findings
      suggest that PSMB8 KQ genotype could increase the risk to develop
      hypersensitivity pneumonitis.

PMID- 20153158
TI  - Long-term therapy with inhaled iloprost in patients with pulmonary hypertension.
AB  - AIMS: To investigate the long-term safety of inhaled iloprost in patients with
      pulmonary hypertension (pH), including idiopathic PAH (IPAH group) and other
      forms of pulmonary hypertension (PHother). METHODS AND RESULTS: Sixty-three
      patients (IPAH group, n=40, PHother n=23) were enrolled to receive inhaled
      iloprost either from baseline or after 3 months in a prospective, open-label 2
      year study. Iloprost was inhaled 6-9 times daily with a night pause employing a
      jet nebulizer delivering an inhaled single dose of 4microg at the mouthpiece. In
      the case of side effects the single dose was reduced to 2microg. Sixty patients
      received at least 1 dose of inhaled iloprost. Thirty-six patients completed at
      least 630 days of therapy (25 IPAH, 11 PHother), 19 patients dropped out
      prematurely and 8 patients died (3 IPAH, 5 PHother). There were no drug-induced
      toxicities and only mild to moderate side effects. The most common side effects
      were coughing and flushing. Two-year survival was estimated at 85% (IPAH group
      91%, PHother 78%). A modified analysis was performed to correct for differential
      drop-out. It included follow-up data from the premature discontinuations and
      revealed a 2-year survival of 87% [95% CI, 76%-98%] in the IPAH group while the
      predicted survival was 63%. The iloprost dose increased by 16% over 2 years.
      CONCLUSION: Inhaled iloprost is well tolerated as long-term therapy and no
      substantial dose increase is required. Although uncontrolled, the data suggest a
      long-term clinical benefit from continued therapy with inhaled iloprost.

PMID- 20153159
TI  - Regulatory T cells in transplantation: does extracellular adenosine triphosphate
      metabolism through CD39 play a crucial role?
AB  - Despite tremendous improvements in short-term renal allograft survival, many
      patients still have chronic rejection or side effects of nonspecific
      immunosuppression. The discovery of Foxp3(+) regulatory T cells (Tregs) has
      revolutionized the concepts in immunoregulation and offers perspectives for
      overcoming rejection. Recently, a subset of Foxp3(+)CD39(+) effector/memory-like
      Tregs (T(REM)) was identified. The role of CD39(+) Tregs in immunoregulation is
      supported by the occurrence of alopecia areata and experimental autoimmune
      encephalomyelitis in CD39-deficient mice and by the failure of CD39(-) Tregs to
      suppress contact hypersensitivity. In humans, CD39 polymorphisms have been
      associated with diabetes and nephropathy, and multiple sclerosis patients have
      reduced numbers of blood CD39(+) Tregs. Preliminary experiments in a murine
      transplantation model showed that CD39(+) Tregs can determine allograft outcome.
      CD39 degrades the extracellular adenosine triphosphate (ATP) released during
      tissue injury, which otherwise would trigger inflammation. Currently, our groups
      are assessing the role of CD39(+) Tregs and extracellular ATP metabolism in
      clinical transplantation and whether tolerogenic Treg profiles possess
      immunopredictive value, envisioning the development of clinical trials using
      CD39(+) Treg-based vaccination for autoimmunity or transplantation. This is a
      comprehensive review on the fundamentals of Treg biology, the potential role of
      ATP metabolism in immunoregulation, and the potential use of Treg-based
      immunotherapy in transplantation.

PMID- 20153160
TI  - Large-scale direct shear testing of municipal solid waste.
AB  - Large direct shear testing (300 mm x 300 mm box) of municipal solid waste (MSW)
      collected from a landfill located in the San Francisco Bay area was performed to
      gain insight on the shear response of MSW. The study investigated the effects of
      waste composition, confining stress, unit weight, and loading rate on the stress
      displacement response and shear strength of MSW. The amount and orientation of
      the fibrous waste materials in the MSW were found to play a critical role. The
      fibrous material had little effect on the MSW's strength when it was oriented
      parallel to the shear surface, as is typically the case when waste material is
      compressed vertically and then tested in a direct shear apparatus. Tests in which
      the fibrous material was oriented perpendicular to the horizontal shear surface
      produced significantly stronger MSW specimens. The test results indicate that
      confining stress and loading rate are also important factors. Based on 109 large
      scale direct shear tests, the shear strength of MSW at low moisture contents is
      best characterized by cohesion=15 kPa, friction angle=36 degrees at a normal
      stress of 1 atmosphere, and a decrease in the friction angle of 5 degrees for
      every log-cycle increase in normal stress.

PMID- 20153161
TI  - Mineralogy and pore water chemistry of a boiler ash from a MSW fluidized-bed
      incinerator.
AB  - This paper presents an investigation of the mineralogy and pore water chemistry
      of a boiler ash sampled from a municipal solid waste fluidized-bed incinerator,
      subject to 18 months of dynamic leaching in a large percolation column
      experiment. A particular focus is on the redox behaviour of Cr(VI) in relation to
      metal aluminium Al(0), as chromium may represent an environmental or health
      hazard. The leaching behaviour and interaction between Cr(VI) and Al(0) are
      interpreted on the basis of mineralogical evolutions observed over the 18-month
      period and of saturation indices calculated with the geochemical code PhreeqC and
      reviewed thermodynamic data. Results of mineralogical analyses show in particular
      the alteration of mineral phases during leaching (e.g. quartz and metal aluminium
      grains), while geochemical calculations suggest equilibria of percolating fluids
      with respect to specific mineral phases (e.g. monohydrocalcite and aluminium
      hydroxide). The combination of leaching data on a large scale and mineralogical
      analyses document the coupled leaching behaviour of aluminium and chromium, with
      chromium appearing in the pore fluids in its hexavalent and mobile state once
      metal aluminium is no longer available for chromium reduction.

PMID- 20153162
TI  - Gold nanoparticle-based colorimetric assay for cancer diagnosis.
AB  - A novel gold nanoparticle (GNP)-based colorimetric assay was developed for cancer
      diagnosis. This system is based on the noncrosslinking aggregation mechanism with
      a cationic protein kinase C (PKC) alpha-specific peptide substrate, which is used
      as a coagulant of citrate-coated GNP with anionic surface charges. The
      phosphorylation of peptide substrates by PKCalpha suppressed GNP aggregation,
      resulting in a red color, but in the case of non-phosphorylation, the color of
      the GNP solution changed from red to blue, indicating particle aggregation.
      Moreover, a correlation between the color change of the GNP dispersions and the
      level of activated PKCalpha was identified from experiments using cancer cell
      lines, or xenografted mouse cancer and normal mouse tissues. When our system was
      applied to human breast cancers and normal human breast tissues, cancer tissue
      lysates became red in color, indicating GNP dispersion, while all lysates from
      normal tissue turned the GNP solution blue. MALDI-TOF MS analysis and Western
      blotting experiment confirmed that these different results between cancer and
      normal tissues reflected the difference in PKCalpha activity. This study is the
      first report on the application of the GNP-based colorimetric assay to the
      diagnosis of cancer.

PMID- 20153163
TI  - Electrodeless QCM-D for lipid bilayer applications.
AB  - An electrodeless quartz crystal microbalance with dissipation monitoring (QCM-D)
      setup is used to monitor the formation of supported lipid bilayers (SLBs) on bare
      quartz crystal sensor surfaces. The kinetic behavior of the formation of a 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) SLB on SiO(2) surfaces is
      discussed and compared for three cases: (i) a standard SiO(2) film deposited onto
      the gold electrode of a quartz crystal, (ii) an electrodeless quartz crystal with
      a sputter-coated SiO(2) film, and (iii) an uncoated electrodeless quartz crystal
      sensor surface. We demonstrate, supported by imaging the SLB on an uncoated
      electrodeless surface using atomic force microscopy (AFM), that a defect-free,
      completely covering bilayer is formed in all three cases. Differences in the
      kinetics of the SLB formation on the different sensor surfaces are attributed to
      differences in surface roughness. The latter assumption is supported by imaging
      the different surfaces using AFM. We show furthermore that electrodeless quartz
      crystal sensors can be used not only for the formation of neutral SLBs but also
      for positively and negatively charged SLBs. Based on our results we propose
      electrodeless QCM-D to be a valuable technique for lipid bilayer and related
      applications providing several advantages compared to electrode-coated surfaces
      like optical transparency, longer lifetime, and reduced costs.

PMID- 20153164
TI  - Nonribosomal peptide synthetases: structures and dynamics.
AB  - Nonribosomal peptide synthetases (NRPSs) are large multimodular biocatalysts that
      utilize complex regiospecific and stereospecific reactions to assemble
      structurally and functionally diverse peptides that have important medicinal
      applications. During this ribosome-independent peptide synthesis, catalytic
      domains of NRPS select, activate or modify the covalently tethered reaction
      intermediates to control the iterative chain elongation process and product
      release. Recent advances in structural elucidation of domains, didomains, and an
      entire termination module revealed valuable insights into the mechanism of
      nonribosomal synthesis and are highlighted herein.

PMID- 20153165
TI  - Coupling of the hydrogen and polyhydroxyalkanoates (PHA) production through
      anaerobic digestion from Taihu blue algae.
AB  - Coupling bio-production of hydrogen and polyhydroxyalkanoates (PHA) from Taihu
      blue algae through metabolites circulation was investigated. It was found that
      the pH adjustment, especially basification was more practical and efficient than
      other methods for the pretreatment of blue algae before anaerobic digestion. On
      this occasion, SCOD, biogas accumulation and hydrogen content reached 26 mg/gTS,
      500 mL and 37.2%, and which were 4.3, 1.3 and 14.4 times of those of the control
      group, respectively. Secondly, amounts of both butyric acid and hydrogen could be
      further increased when blue algae was alkali pretreated at pH 13, as the
      accumulation of butyric acid, acetic acid and hydrogen reached 1.7, 1.4 and 3.8
      times compared to those of the control, respectively. Finally, the coupling bio
      production of hydrogen and PHA was conducted through pumping organic residues
      into PHA fermenter from anaerobic digester. Remarkably, it was found that the
      larger the pumping rate of carbon and nitrogen sources supply, the higher the
      yield of DCW and PHA could be expected by Bacillus cereus.

PMID- 20153166
TI  - Competitive transesterification of soybean oil with mixed methanol/ethanol over
      heterogeneous catalysts.
AB  - Methylesters and ethylesters of fatty acids were synthesized using homogeneous
      CH(3)ONa and CH(3)CH(2)ONa, anion exchanged resin, and CaO-La(2)O(3) catalysts.
      Methanol, ethanol, and methanol/ethanol mixtures were used as the alcohol feed
      for transesterification of soybean oil. With a homogeneous catalyst (CH(3)ONa)
      there was essentially no difference in conversion rates between methanolysis and
      ethanolysis in batch reactions. However, with a heterogeneous resin and CaO
      La(2)O(3) catalysts, significant differences in the conversion rates between the
      methanolysis and ethanolysis were observed. The formation rate of methylesters
      over a CaO-La(2)O(3) catalyst was higher than that of ethylesters, which may be
      attributable to a steric hindrance effect. Conversely, with a heterogeneous resin
      catalyst, the conversion rate of ethylester was higher than that of methylesters
      which may be attributable to the surface hydrophobicity of the anion exchanged
      resin. When the transesterification of soybean oil was carried out with an
      equimolar methanol/ethanol mixture, the yield ratio of methylester to ethylester
      formed within the first 30 min was 2.6 for the homogeneous catalyst (0.3%
      CH(3)ONa), and 3.4 for the heterogeneous CaO-La(2)O(3)catalyst. These differences
      in selectivity are likely due to both the higher reactivity of methoxide and to a
      steric hindrance effect of ethoxide on the catalyst surface. In addition, the
      transformation of methylester to ethylester was observed when a methanol/ethanol
      mixture was used.

PMID- 20153167
TI  - Economic assessment of biodiesel production from waste frying oils.
AB  - Waste frying oils (WFO) can be a good source for the production of biodiesel
      because this raw material is not part of the food chain, is low cost and can be
      used in a way that resolves environmental problems (i.e. WFO is no longer thrown
      into the sewage network). The goal of this article is to propose a method to
      evaluate the costs of biodiesel production from WFO to develop an economic
      assessment of this alternative. This method embraces a logistics perspective, as
      the cost of collection of oil from commercial producers and its delivery to
      biodiesel depots or plants can be relevant and is an issue that has been little
      explored in the academic literature. To determine the logistics cost, a
      mathematical programming model is proposed to solve the vehicle routing problem
      (VRP), which was applied in an important urban center in Brazil (Rio de Janeiro),
      a relevant and potential center for biodiesel production and consumption. Eighty
      one biodiesel cost scenarios were compared with information on the
      commercialization of biodiesel in Brazil. The results obtained demonstrate the
      economic viability of biodiesel production from WFO in the urban center studied
      and the relevance of logistics in the total biodiesel production cost.

PMID- 20153168
TI  - Conditioning of sewage sludge with electrolysis: effectiveness and optimizing
      study to improve dewaterability.
AB  - The potential benefits of electrolysis-conditioned sludge dewatering treatment
      were investigated in this paper. Focuses were placed on effectiveness and factors
      affecting such novel application of electrolysis process. Experiments have
      demonstrated that a significant improvement of sludge dewaterability evaluated by
      capillary suction time (CST) could be obtained at a relative low value of
      electrolysis voltage. A Box-Behnken experimental design based on the response
      surface methodology (RSM) was applied to evaluate the optimum of the influencing
      variables. The optimal values for electrolysis voltage, electrode distance and
      electrolysis time are 21 V, 5 cm and 12 min, respectively, at which the CST
      reduction efficiency of 18.8+/-3.1% could be achieved, this agreed with that
      predicted by an established polynomial model in this study.

PMID- 20153169
TI  - Preliminary enrichment and separation of genistein and apigenin from extracts of
      pigeon pea roots by macroporous resins.
AB  - Enrichment and separation of genistein and apigenin from extracts of pigeon pea
      roots were studied using eleven macroporous resins with different physical and
      chemical properties. ADS-5 resin showed the maximum effectiveness among the
      tested resins. The solute affinity towards ADS-5 resin at different temperatures
      was described in terms of Langmuir and Freundlich isotherms, and the equilibrium
      experimental data were well-fitted to the two isotherms. In order to optimize the
      operating parameters for separating genistein and apigenin, dynamic adsorption
      and desorption tests were carried out. After one run treatment with ADS-5 resin,
      the contents of genistein and apigenin in the product were 9.36-fold and 11.09
      fold increased with recovery yields of 89.78% and 93.41%, respectively. The
      process achieved easy and effective enrichment and separation of genistein and
      apigenin by using ADS-5 resin, and it is a promising basis for large-scale
      preparation of genistein and apigenin from pigeon pea or other plants extracts.

PMID- 20153170
TI  - A semi-empirical model for pressurised air-blown fluidized-bed gasification of
      biomass.
AB  - A process model for pressurised fluidized-bed gasification of biomass was
      developed using Aspen Plus simulation software. Eight main blocks were used to
      model the fluidized-bed gasifier, complemented with FORTRAN subroutines nested in
      the programme to simulate hydrocarbon and NH(3) formation as well as carbon
      conversion. The model was validated with experimental data derived from a PDU
      scale test rig operated with various types of biomass. The model was shown to be
      suitable for simulating the gasification of pine sawdust, pine and eucalyptus
      chips as well as forest residues, but not for pine bark or wheat straw.

PMID- 20153171
TI  - Study of the co-deoxy-liquefaction of biomass and vegetable oil for hydrocarbon
      oil production.
AB  - Hydrocarbon oil was obtained by co-deoxy-liquefaction of biomass and vegetable
      oil in the work. Results showed the weight ratio of biomass to vegetable oil
      exerted a great effect on the quality of obtained hydrocarbon oil. The optimum
      weight ratio of biomass to vegetable oil was 4.4:1, when alkanes with the content
      of 50.43% were detected in obtained hydrocarbon oil, with lower oxygen content of
      2.52%, which resulted in higher calorific value-up to 43.36 MJ kg(-1). At the
      same time, removal rate of carbonyl group of vegetable oil in the mixture reached
      at least 75.11%. The overall efficiency of the deoxy-liquefaction of biomass and
      the decarboxylation of vegetable oil were both enhanced by adding vegetable oil
      into biomass. Compared with the oils obtained from vegetable oil and biomass,
      respectively, distribution of hydrocarbon oil obtained from the mixture was much
      more similar to that of diesel oil.

PMID- 20153172
TI  - Simultaneous removal of organic matter and nitrogen from milking parlor
      wastewater by a magnetic activated sludge (MAS) process.
AB  - The magnetic activated sludge (MAS) process is a modification of the conventional
      activated sludge process to improve the solid-liquid separation characteristics.
      It was developed to reduce the production of excess sludge and the time required
      for the conventional activated sludge process. In this study, actual milking
      parlor wastewater was treated with a MAS process and no sludge was removed. The
      effectiveness of continuous aeration and intermittent aeration in removing
      organic matter and nitrogen were compared. Both processes were highly efficient
      at removing chemical oxygen demand (COD) (averaged 91% removal) and ammonium
      nitrogen (NH(4)-N) (averaged 99% removal). In marked contrast to the continuous
      aeration process, the 30-min aeration/90-min non-aeration cycle of the
      intermittent aeration process rapidly reduced the nitrate nitrogen (NO(3)-N)
      concentration to near-zero. This result indicates that NO(3)-N was almost
      completely denitrified via nitrite nitrogen (NO(2)-N) to nitrogen gas. Removal of
      organic material and nitrogen can be considered to have occurred simultaneously
      in the single tank of the MAS process.

PMID- 20153173
TI  - Methane production in low-cost, unheated, plug-flow digesters treating swine
      manure and used cooking grease.
AB  - A co-digestion investigation was conducted using small-scale digesters in Costa
      Rica to optimize their ability to treat animal wastewater and produce renewable
      energy. Increases in methane production were quantified when swine manure was co
      digested with used cooking grease in plug-flow digesters that operated at ambient
      temperate without mixing. The co-digestion experiments were conducted on 12 field
      scale digesters (250 L each) using three replications of four treatment groups:
      the control (T0), which contained only swine manure and no waste oil, and T2.5,
      T5, and T10, which contained 2.5%, 5%, and 10% used cooking grease (by volume)
      combined with swine manure. The T2.5 treatment had the greatest methane (CH(4))
      production (45 L/day), a 124% increase from the control, with a total biogas
      production of 67.3 L/day and 66.9% CH(4) in the produced biogas. Increasing the
      grease concentration beyond T2.5 produced biogas with a lower percentage of
      CH(4), and thus, did not result in any additional benefits. A batch study showed
      that methane production could be sustained for three months in digesters that co
      digested swine manure and used cooking grease without daily inputs. The
      investigation proved that adding small amounts of grease to the influent is a
      simple way to double energy production without affecting other digester benefits.

PMID- 20153174
TI  - Evaluation of a membrane biological reactor for reclaiming water, alkalinity,
      salts, phosphorus, and protein contained in a high-strength aquacultural
      wastewater.
AB  - The capacity of a membrane biological reactor to provide nitrification,
      denitrification, and enhanced biological phosphorus removal of a high-strength
      aquaculture backwash flow (control condition), or the same flow amended with
      100mg/L of NO(3)-N and 3mg/L of dissolved P (test condition), was assessed using
      only endogenous carbon. Permeate TSS and cBOD(5) concentrations were <1mg/L under
      control and test conditions, achieving 99.97-100% removal efficiencies,
      respectively. Permeate TN concentrations were 1.8+/-0.5mg/L and 2.1+/-1.4 mg/L,
      while permeate TP concentrations were 0.05+/-0.01 mg/L and 0.10+/-0.03 mg/L,
      respectively, under control and test conditions. Our findings suggest that
      permeate flow could be reclaimed to recycle alkalinity, salts, and heat for fish
      culture and that the waste activated sludge does not produce metals
      concentrations that would prevent its land application (reclaiming phosphorus) or
      prevent its use as a protein source in animal feeds.

PMID- 20153175
TI  - The biomass yielding process of xenobiotic degradation.
AB  - Yields of activated sludge and an Arthrobacter sp. biomass on organic xenobiotic
      2,4-dichlorophenoxyacetic acid (2,4-D) and on the intermediates of selected 2,4-D
      metabolism pathways were measured. Activated sludge yield on 2,4-D was lower by
      approximately 24-45% compared to the combined yields produced separately by the
      lower intermediates. For activated sludge, cell synthesis only consumed 33% of
      the electrons generated from 2,4-D oxidation, while the other 67% were used for
      energy. The high energy consumption, which was the primary cause of low activated
      sludge yield from 2,4-D degradation, occurred mainly in the catabolism of 2,4-D.
      The degrader sludge supplied this catabolism energy demand with the ATP contained
      in the biomass. As a result, the sludge's ATP contents suffered a deficit that
      was not fully remunerated after 2,4-D was degraded. Metabolism of the lower
      intermediates provided materials for further biomass growth and refilled part of
      the energy initially consumed.

PMID- 20153176
TI  - Using FTIR spectroscopy for rapid determination of lipid accumulation in response
      to nitrogen limitation in freshwater microalgae.
AB  - In this study Fourier transform infrared micro-spectroscopy (FTIR) was used to
      determine lipid and carbohydrate content over time in the freshwater microalgae
      Chlamydomonas reinhardtii and Scenedesmus subspicatus grown in batch culture in
      limiting concentrations of nitrogen (N). Both algae exhibited restricted cell
      division and increased cell size following N-limitation. FTIR spectra of cells in
      N-limited media showed increasing lipid:amide I and carbohydrate:amide I ratios
      over time. The use of lipid- and starch-staining dyes confirmed that the observed
      ratio changes were due to increased lipid and carbohydrate synthesis. These
      results demonstrate rapid metabolic responses of C. reinhardtii and S.
      subspicatus to changing nutrient availability, and indicate the efficiency of
      FTIR as a reliable method for high-throughput determination of lipid induction.

PMID- 20153177
TI  - The statistically optimized production of poly(gamma-glutamic acid) by batch
      fermentation of a newly isolated Bacillus subtilis RKY3.
AB  - For the production of poly(gamma-glutamic acid), a newly isolated Bacillus sp.
      RKY3 was phylogenetically identified as Bacillus subtilis based on its 16S rRNA
      gene sequence. The culture medium for the production of poly(gamma-glutamic acid)
      by B. subtilis RKY3 was optimized statistically. The parameters significantly
      affecting poly(gamma-glutamic acid) production were found to be glycerol,
      glutamic acid, yeast extract, and K(2)HPO(4). A further advanced statistical
      approach, central composite design, found the optimum levels of the screened
      variables as follows (gl(-1)): glycerol 17.6, glutamic acid 59.6; yeast extract
      2.7; K(2)HPO(4) 2.3. The predicted response as poly(gamma-glutamic acid)
      production under the statistically optimized conditions was 48.5 g l(-1), which
      was only 0.4% different from the maximum poly(gamma-glutamic acid) concentration
      (48.7 g l(-1)) observed at the validation experiment using 7-l lab-scale
      fermentor containing 3 l of working volume.

PMID- 20153178
TI  - Continuous high-solids corn liquefaction and fermentation with stripping of
      ethanol.
AB  - Removal of ethanol from the fermentor during fermentation can increase
      productivity and reduce the costs for dewatering the product and coproduct. One
      approach is to recycle the fermentor contents through a stripping column, where a
      non-condensable gas removes ethanol to a condenser. Previous research showed that
      this approach is feasible. Savings of $0.03 per gallon were predicted at 34% corn
      dry solids. Greater savings were predicted at higher concentration. Now the
      feasibility has been demonstrated at over 40% corn dry solids, using a continuous
      corn liquefaction system. A pilot plant, that continuously fed corn meal at more
      than one bushel (25 kg) per day, was operated for 60 consecutive days,
      continuously converting 95% of starch and producing 88% of the maximum
      theoretical yield of ethanol. A computer simulation was used to analyze the
      results. The fermentation and stripping systems were not significantly affected
      when the CO(2) stripping gas was partially replaced by nitrogen or air,
      potentially lowering costs associated with the gas recycle loop. It was concluded
      that previous estimates of potential cost savings are still valid.

PMID- 20153179
TI  - Methane production from rice straw with acclimated anaerobic sludge: effect of
      phosphate supplementation.
AB  - Rice straw particles were directly used as substrate for anaerobic digestion with
      acclimated sludge under room temperature and different levels of phosphate. Two
      obvious biogas production peaks were observed for all reactors, with biogas or
      methane yields of (0.33-0.35)m(3)/kg-VS loaded or (0.27-0.29)m(3) CH(4)/kg-VS
      loaded and average methane contents of 75.9-78.2%. A separated two-stage first
      order kinetic model was developed in this study and showed a good fit to the
      experimental data when this complicated process was divided into two stages. The
      average biogas and methane production rate constants were (0.027-0.031)d(-1) and
      (0.028-0.033)d(-1), respectively, increased by 2-3 times in the second stages
      than those in the first. The results indicated that an adequate level of
      phosphate addition (465 mg-P/L) could accelerate the biogasification process: 7
      13 days earlier appearance of the two peaks and shorter time needed for complete
      biogasification of rice straw.

PMID- 20153180
TI  - Biotransformation of ferulic acid to 4-vinylguaiacol by a wild and a diploid
      strain of Aspergillus niger.
AB  - Ferulic acid biotransformation has a number of interesting industrial uses.
      Ferulic acid biotransformation by the wild strain Aspergillus niger C28B25 and a
      diploid strain DAR2, obtained by parasexual recombination, was studied. The wild
      strain of A.niger C28B25 biotransforms ferulic acid to vanillic acid (VA); while
      the diploid strain DAR2 preferentially decarboxylates ferulic acid to 4
      vinylguaiacol (4VG). The latter was identified by mass spectroscopy, (1)H and
      (13)C nuclear magnetic resonance spectroscopy, and quantified by HPLC. The
      diploid strain A.niger DAR2 and the wild strain showed a ferulic acid conversion
      of 64% and 36%, respectively. Molar yields show that the formation of 4VG was
      preferred, being as much as 4.4 times higher than the formation of VA in diploid
      strain cultures. Differential regulation of enzymes involved in the
      biotransformation of ferulic acid may explain the accumulation of 4VG by diploid
      DAR2. This strain produced both 4VG and VA.

PMID- 20153181
TI  - Selected properties of particleboard panels manufactured from rice straws of
      different geometries.
AB  - The objective is to evaluate the primary mechanical and physical properties of
      particleboard made from hammer-milled rice straw particles of six different
      categories and two types of resins. The results show the performance of straw
      particleboards is highly dependent upon the straw particle size controlled by the
      opening size of the perforated plate inside the hammer-mill. The static bending
      and internal bonding strength of polymeric diphenylmethane diisocyanate (pMDI)
      resin-bonded boards initially increase then decrease with decreased particle
      size. The thickness swelling, water absorption, and linear expansion of
      particleboards decrease with increasing particle size. Compared with pMDI resin
      bonded panels, the rice straw particleboard bonded using urea-formaldehyde resin
      exhibits much poorer performance. The optimized panel properties, obtained when
      using 4% pMDI and straw particles hammer milled with a 3.18 mm opening perforated
      plate, exceeded the M-2 specification of American National Standard for Wood
      Particleboard.

PMID- 20153182
TI  - Hybrid composites made from recycled materials: moisture absorption and thickness
      swelling behavior.
AB  - In this research, hybrid composite materials were made from the combination of
      recycled newspaper fiber (RNF) and poplar wood flour (PWF) as reinforcement,
      recycled polypropylene (RPP) as polymer matrix, and maleated polypropylene (MAPP)
      as coupling agent, by using injection molding. The effects of weight fractions of
      fibers and coupling agent concentration on the physical properties of the
      composites in terms of water absorption and thickness were studied. Composites
      containing more fraction of RNF exhibited maximum water absorption during the
      whole duration of immersion. This effect can be explained by the presence of a
      high amount of holocellulose present in the RNF, compared to the PWF. The
      addition of MAPP exhibited a beneficial effect on both the water absorption and
      thickness swelling by improving the quality of adhesion between polymer and
      fibers.

PMID- 20153183
TI  - Design and synthesis of novel deoxybenzoin derivatives as FabH inhibitors and
      anti-inflammatory agents.
AB  - Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step
      of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria.
      The important role of this essential enzyme combined with its unique structural
      features and ubiquitous occurrence in bacteria has made it an attractive new
      target for the development of new FabH inhibitors. The synthesis and biological
      evaluation halide-deoxybenzoins derivatives are described in this Letter. Potent
      FabH inhibitory and selective anti-Gram-negative bacteria activities were
      observed in deoxybenzoin derivatives. Furthermore, compound 19 was able to reduce
      the ECE-induced IL-8 production in gastric mucosal cells significantly. Based on
      the biological data and molecular docking, compound 19 is a potential FabH
      inhibitor and anti-inflammatory agent deserving further research.

PMID- 20153184
TI  - Triterpene compounds isolated from Acer mandshuricum and their anti-inflammatory
      activity.
AB  - In our preliminary screening study on the anti-inflammatory activity, a new
      triterpene compound, aceranol acetate (1), was isolated along with five known
      compounds: beta-amyrin acetate (2); glutinol acetate (3); friedelin (4); glutinol
      (5); (3beta)-d-glucopyranoside-stigmast-5-en-3-yl (6), from the stems and leaves
      of Acer mandshuricum. The structure of the new triterpene was determined to be
      5alpha,6alpha-epidioxy-5beta,6beta-epoxy-9,13-dimethyl-25,26-dinoroleanan-3beta
      ol acetate by spectroscopic studies. Compounds 2-6 were isolated from this plant
      for the first. Five triterpene compounds (1-5) showed significant cytotoxic
      activity with GI(50) in the range of 11.1-17.9microM, whereas steroid compound
      (6) exhibited moderate activity against four human cancer cell lines (HL-60, SK
      OV-3, A549, and HT-29). Furthermore, the anti-inflammatory effects of compounds 1
      6 in the non-cytotoxic concentrations (1-100nM) were evaluated for the inhibitory
      activity of TNF-alpha secretion in the lipopolysaccharide (LPS)-stimulated murine
      RAW264.7 macrophage cell line. Among the compounds tested, compound 2 showed the
      strongest anti-inflammatory activity with the inhibition rate up to 38.40% at the
      concentration of 100nM, whereas other five compounds (2-6) exhibited moderate
      activity.

PMID- 20153185
TI  - Iodine scanning of a phenazine inhibitor of vacuolar sorting.
AB  - Affinity reagents are often used to address the target identification problem in
      chemical genetics. The design of such reagents so that the linker does not
      occlude interactions with protein targets is an ongoing challenge. This work
      describes a systematic approach to synthesize derivatives of a bioactive that
      should avoid interference with binding to targets and be readily converted to
      affinity reagents.

PMID- 20153186
TI  - S1P receptor mediated activity of FTY720 phosphate mimics.
AB  - Various carboxylic acids, phosphonic acids, sulfonic acids, tetrazoles as well as
      sulfonylhydantoins were prepared as phosphate mimics of the chiral aminophosphate
      1-P to act as agonists on the S1P(1) receptor. It was found that amino
      phosphonates and amino carboxylates are potent S1P(1) binders. beta-Amino acid 11
      could be shown to reversibly reduce blood lymphocyte counts in rats after po
      administration.

PMID- 20153187
TI  - Dioxo-triazines as a novel series of cathepsin K inhibitors.
AB  - A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS.
      A rapid exploratory programme led to the discovery of potent and selective
      cathepsin K inhibitors, typified by compound 24 which displayed IC(50) values of
      17nM against catK and >10,000nM in catL, catB and catS assays.

PMID- 20153188
TI  - Structure-activity relationships of norepinephrine reuptake inhibitors with
      benzothiadiazine dioxide or dihydrosulfostyril cores.
AB  - Two related series of selective norepinephrine reuptake inhibitors were
      synthesized based on 3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide or 3,4
      dihydrosulfostyril cores, and screened for monoamine reuptake inhibition.
      Structure-activity relationships were determined for the series' in vitro potency
      and selectivity versus serotonin or dopamine transporter inhibition, and analogs
      based on both cores were identified as potent and selective NRIs. The 3,4
      dihydrosulfostyril series was further tested for microsome stability, and
      compound 16j, which was optimized for both potency and stability, showed efficacy
      in an in vivo model of thermoregulatory dysfunction.

PMID- 20153189
TI  - SAR of PXR transactivation in benzimidazole-based IGF-1R kinase inhibitors.
AB  - The SAR of PXR transactivation by 3-(benzimidazol-2-yl)-pyridine-2-one based ATP
      competitive inhibitors of Insulin-like Growth Factor 1 Receptor kinase (IGF-1R)
      is discussed. Compounds without PXR transactivation, with in vivo antitumor
      activity, reduced protein binding and improved oral exposure are presented.

PMID- 20153190
TI  - Design, synthesis, and evaluation of indole compounds as novel inhibitors
      targeting Gp41.
AB  - A series of indole ring containing compounds were designed based on the structure
      of the gp41 complex in the region of the hydrophobic pocket. These compounds were
      synthesized using a Suzuki Coupling reaction, and evaluated using a fluorescence
      binding assay and cell-cell fusion assay. The observed inhibition constant of
      compound 7 was 2.1microM, and the IC(50) for cell-cell fusion inhibition was
      1.1microM. Assay data indicated that 7 is a promising lead compound for
      optimization into an effective low molecular weight fusion inhibitor.

PMID- 20153191
TI  - Effect of 3'-end capping of aptamer with various 2',4'-bridged nucleotides:
      Enzymatic post-modification toward a practical use of polyclonal aptamers.
AB  - The capping of the 3'-ends of thrombin binding aptamers (TBAs) with bridged
      nucleotides increased the nuclease resistances and the stabilities in human
      serum. The binding abilities of the aptamers were not affected by the capping.
      The capping could be simply executed via a one step enzymatic process using 2',4'
      bridged nucleoside 5'-triphosphate and terminal deoxynucleotidyl transferase.

PMID- 20153192
TI  - Regulation of gustatory physiology and appetitive behavior by the Drosophila
      circadian clock.
AB  - BACKGROUND: Circadian regulation of chemosensory processes is common in animals,
      but little is known about how circadian clocks control chemosensory systems or
      the consequences of rhythms in chemosensory system function. Taste is a major
      chemosensory gate used to decide whether or not an animal will eat, and the main
      taste organ in Drosophila, the proboscis, harbors autonomous circadian
      oscillators. Here we examine gustatory physiology, tastant-evoked appetitive
      behavior, and food ingestion to understand clock-dependent regulation of the
      Drosophila gustatory system. RESULTS: Here we report that single-unit responses
      from labellar gustatory receptor neurons (GRNs) to attractive and aversive
      tastants show diurnal and circadian rhythms in spike amplitude, frequency, and
      duration across different classes of gustatory sensilla. Rhythms in
      electrophysiological responses parallel behavioral rhythms in proboscis extension
      reflex. Molecular oscillators in GRNs are necessary and sufficient for rhythms in
      gustatory responses and drive rhythms in G protein-coupled receptor kinase 2
      (GPRK2) expression that mediate rhythms in taste sensitivity. Eliminating clock
      function in certain GRNs increases feeding and locomotor activity, mimicking a
      starvation response. CONCLUSIONS: Circadian clocks in GRNs control neuronal
      output and drive behavioral rhythms in taste responses that peak at a time of day
      when feeding is maximal in flies. Our results argue that oscillations in GPRK2
      levels drive rhythms in gustatory physiology and behavior and that GRN clocks
      repress feeding. The similarity in gustatory system organization and feeding
      behavior in flies and mammals, as well as diurnal changes in taste sensitivity in
      humans, suggest that our results are relevant to the situation in humans.

PMID- 20153193
TI  - Both interaction surfaces within cohesin's hinge domain are essential for its
      stable chromosomal association.
AB  - BACKGROUND: The cohesin complex that mediates sister chromatid cohesion contains
      three core subunits: Smc1, Smc3, and Scc1. Heterotypic interactions between Smc1
      and Smc3 dimerization domains create stable V-shaped Smc1/Smc3 heterodimers with
      a hinge at the center and nucleotide-binding domains (NBDs) at the ends of each
      arm. Interconnection of each NBD through their association with the N- and C
      terminal domains of Scc1 creates a tripartite ring, within which sister DNAs are
      thought to be entrapped (the ring model). Crystal structures show that the
      Smc1/Smc3 hinge has a toroidal shape, with independent "north" and "south"
      interaction surfaces on an axis of pseudosymmetry. The ring model predicts that
      sister chromatid cohesion would be lost by transient hinge opening. RESULTS: We
      find that mutations within either interface weaken heterodimerization of isolated
      half hinges in vitro but do not greatly compromise formation of cohesin rings in
      vivo. They do, however, reduce the residence time of cohesin on chromosomes and
      cause lethal defects in sister chromatid cohesion. This demonstrates that mere
      formation of rings is insufficient for cohesin function. Stable cohesion requires
      cohesin rings that cannot easily open. CONCLUSIONS: Either the north or south
      hinge interaction surface is sufficient for the assembly of V-shaped Smc1/Smc3
      heterodimers in vivo. Any tendency of Smc proteins with weakened hinges to
      dissociate will be suppressed by interconnection of their NBDs by Scc1. We
      suggest that transient hinge dissociation caused by the mutations described here
      is incompatible with stable sister chromatid cohesion because it permits
      chromatin fibers to escape from cohesin rings.

PMID- 20153194
TI  - Distinct retinal pathways drive spatial orientation behaviors in zebrafish
      navigation.
AB  - Navigation requires animals to adjust ongoing movements in response to pertinent
      features of the environment and select between competing target cues. The
      neurobiological basis of navigational behavior in vertebrates is hard to analyze,
      partly because underlying neural circuits are experience dependent. Phototaxis in
      zebrafish is a hardwired navigational behavior, performed at a stage when larvae
      swim by using a small repertoire of stereotyped movements. We established
      conditions to elicit robust phototaxis behavior and found that zebrafish larvae
      deploy directional orienting maneuvers and regulate forward swimming speed to
      navigate toward a target light. Using genetic analysis and targeted laser
      ablations, we show that retinal ON and OFF pathways play distinct roles during
      phototaxis. The retinal OFF pathway controls turn movements via retinotectal
      projections and establishes correct orientation by causing larvae to turn away
      from nontarget areas. In contrast, the retinal ON pathway activates the
      serotonergic system to trigger rapid forward swimming toward the target.
      Computational simulation of phototaxis with an OFF-turn, ON-approach algorithm
      verifies that our model accounts for key features of phototaxis and provides a
      simple and robust mechanism for behavioral choice between competing targets.

PMID- 20153195
TI  - Circadian clock gene Bmal1 is not essential; functional replacement with its
      paralog, Bmal2.
AB  - Most of the central circadian clock genes in the mouse exist as paralog pairs
      (Per1 and Per2, Cry1 and Cry2, Clock and Npas2) in which each gene of the pair
      must be knocked out to confer arrhythmicity. The only exception to this pattern
      is Bmal1 (also known as Mop3), the single knockout of which confers
      arrhythmicity, despite the presence of its paralog, Bmal2 (also known as Mop9).
      The knockout of Bmal1 also has significant effects on longevity, metabolism, etc.
      These results have led to the conclusion that Bmal1 is a singularly essential
      clock gene and that Bmal2 has a minimal role in the clock system. In contrast, we
      find that expression of Bmal2 from a constitutively expressed promoter can rescue
      the clock and metabolic phenotypes of Bmal1-knockout mice, including rhythmic
      locomotor activity, rhythmic metabolism, low body weight, and enhanced fat
      deposition. Combined with the data of Bunger and colleagues, who reported that
      knockout of Bmal1 downregulates Bmal2, we conclude that Bmal1 and Bmal2 form a
      circadian paralog pair that is functionally redundant and that, in the mouse,
      Bmal2 is regulated by Bmal1 such that knockout of Bmal1 alone results in a
      functionally double Bmal1 and Bmal2 knockout. Therefore, the role(s) of Bmal2 may
      be more important than has been appreciated heretofore.

PMID- 20153196
TI  - The kinesin-8 Kif18A dampens microtubule plus-end dynamics.
AB  - Motility is a fundamentally important property of most members of the kinesin
      superfamily, but a rare subset of kinesins are also able to alter microtubule
      dynamics. At kinetochore-microtubule plus ends, the kinesin-8 family member
      Kif18A is essential to align mitotic chromosomes at the spindle equator during
      cell division, but how it accomplishes this function is unclear. We report here
      that Kif18A is a plus-end-directed motor that inhibits the polymerization
      dynamics of microtubule plus ends without destabilizing them, distinguishing
      Kif18A from the budding yeast ortholog Kip3. In interphase cells, Kif18A uses
      this activity to reduce the overall dynamicity of microtubule plus ends and
      effectively constrains the distance over which plus ends grow and shrink. Our
      findings suggest that kinesin-8 family members have developed biochemically
      distinct activities throughout evolution and have implications for how Kif18A
      affects kinetochore-microtubule plus-end dynamics during mitosis in animal cells.

PMID- 20153197
TI  - A negative feedback signal that is triggered by peril curbs honey bee
      recruitment.
AB  - Decision making in superorganisms such as honey bee colonies often uses self
      organizing behaviors, feedback loops that allow the colony to gather information
      from multiple individuals and achieve reliable and agile solutions. Honey bees
      use positive feedback from the waggle dance to allocate colony foraging effort.
      However, the use of negative feedback signals by superorganisms is poorly
      understood. I show that conspecific attacks at a food source lead to the
      production of stop signals, communication that was known to reduce waggle dancing
      and recruitment but lacked a clear natural trigger. Signalers preferentially
      targeted nestmates visiting the same food source, on the basis of its odor.
      During aggressive food competition, attack victims increased signal production by
      43 fold. Foragers that attacked competitors or experienced no aggression did not
      alter signal production. Biting ambush predators also attack foragers at flowers.
      Simulated biting of foragers or exposure to bee alarm pheromone also elicited
      signaling (88-fold and 14-fold increases, respectively). This provides the first
      clear evidence of a negative feedback signal elicited by foraging peril to
      counteract the positive feedback of the waggle dance. As in intra- and
      intercellular communication, negative feedback may play an important, though
      currently underappreciated, role in self-organizing behaviors within
      superorganisms.

PMID- 20153198
TI  - CRT-1/calreticulin and the E3 ligase EEL-1/HUWE1 control hemidesmosome maturation
      in C. elegans development.
AB  - Hemidesmosomes connect the extracellular matrix (ECM) to intermediate filaments
      through ECM receptors and plakins (plectin and BPAG1e). They affect tissue
      integrity, wound healing, and carcinoma invasion. Although biochemical and time
      lapse studies indicate that alpha6beta4-integrin (ECM receptor) and plectin play
      a central role in modulating hemidesmosome disassembly, the mechanisms
      controlling hemidesmosome biogenesis in vivo remain poorly understood. The
      nematode C. elegans provides a powerful genetic model to address this issue. We
      performed a genome-wide RNA interference screen in C. elegans, searching for
      genes that decrease the viability of a weak VAB-10A/plakin mutant. We identified
      14 genes that have human homologs with predicted roles in different cellular
      processes. We further characterized two genes encoding the chaperone CRT
      1/calreticulin and the HECT domain E3 ubiquitin ligase EEL-1/HUWE1. CRT-1
      controls by as little as 2-fold the abundance of UNC-52/perlecan, an essential
      hemidesmosome ECM ligand. Likewise, EEL-1 fine tunes by 2-fold the abundance of
      myotactin, the putative hemidesmosome ECM receptor. CRT-1 and EEL-1 activities,
      and by extension other genes identified in our screen, are essential during
      embryonic development to enable hemidesmosomes exposed to mechanical tension to
      mature into a tension-resistant form. Our findings should help understand how
      hemidesmosome dynamics are regulated in vertebrate systems.

PMID- 20153200
TI  - WITHDRAWN: 15-year follow-up of PFC posterior cruciate retaining total knee
      arthroplasty.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 20153199
TI  - Drosophila timeless2 is required for chromosome stability and circadian
      photoreception.
AB  - In Drosophila, there are two timeless paralogs, timeless1 (tim1) and timeless2
      (tim2, or timeout). Phylogenetic analyses suggest that tim1 originated as a
      duplication of tim2 around the time of the Cambrian explosion. The function of
      tim1 as a canonical circadian component is well established, but the role of tim2
      in the fly is poorly understood. Many organisms possess a single tim2-like gene
      that has been implicated in DNA synthesis and, in the case of mammals, somewhat
      controversially, in circadian rhythmicity. Here we analyze the structure and the
      functional role of fly tim2. tim2 is a large locus (approximately 75 kb) that
      harbors several transcribed intronic sequences. Using insertional mutations and
      tissue-specific RNA interference-mediated downregulation, we find that tim2 is an
      essential gene required for normal DNA metabolism and chromosome integrity.
      Moreover, tim2 is involved in light entrainment of the adult circadian clock, via
      its expression in the T1 basket cells of the optic lobes. tim2's residual role in
      light entrainment thus provides an evolutionary link that may explain why its
      derived paralog, tim1, came to play such a major role in both circadian
      photosensitivity and core clock function.

PMID- 20153201
TI  - Conservative secondary structure motif of streptavidin-binding aptamers generated
      by different laboratories.
AB  - Aptamers that are selected in vitro from random pools of DNA or RNA molecules by
      SELEX (Systematic evolution of ligands by exponential enrichment) technique have
      been extensively explored for analytical and biomedical applications. Although
      many aptamers with high affinity and specificity against specific ligands have
      been reported, there is still a lack of well characterized DNA aptamers. Here we
      report the selection of a group of aptamer candidates (85 mer) against
      streptavidin. Through comparing the predicted secondary structures of all the
      candidates, a conservative bulge-hairpin structure section (about 29 mer) was
      found, and then it was determined to be the binding motif to streptavidin. This
      binding motif was further discovered to also exist in streptavidin-binding
      aptamers (SBAs) selected by three other laboratories using different methods. The
      primary sequences of this secondary structure motif are very different, only
      several nucleotides in the loop and bulge area are critical for binding and other
      nucleotides are variable. The streptavidin binding of all the SBAs could be
      competed by biotin implying that they bind to the same site on streptavidin.
      These results suggest that the evolution of SBA is predominated by specific
      groups on streptavidin. The highly variable sequence composition of streptavidin
      binding aptamer would make the design of aptameric sensor or device based on
      streptavidin more flexible and easy.

PMID- 20153202
TI  - Synthesis and characterization of novel 1,2,4-triazine derivatives with
      antiproliferative activity.
AB  - A series of novel small molecules with a 1,2,4-triazine scaffold was obtained
      according to a recently published and highly efficient synthetic route. Screening
      for antiproliferative and cytotoxic activity revealed distinct anticancer effects
      against the human leukemia cell line K-562 combined with a remarkable low
      cytotoxicity. All compounds were in agreement with the 'rule-of-five' claims by
      Lipinski and calculated logP(calc) values were experimentally confirmed
      (logP(exp)). For the most active compounds, in vitro serum albumin binding was
      investigated and structure-activity relationships were established.

PMID- 20153203
TI  - Characterization of anticancer properties of 2,6-diisopropylphenol
      docosahexaenoate and analogues in breast cancer cells.
AB  - The present study describes the characterization and evaluation of novel
      anticancer conjugates, 2,6-diisopropylphenol-docosahexaenoate (PP-DHA), and its
      analogues including 2,4-diisopropylphenol-docosahexaenoate (DIPP-DHA), 2
      isopropylphenol-docosahexaenoate (IPP-DHA), 2-cyclohexanephenol-docosahexaenoate
      (CHP-DHA) and phenol-docosahexaenoate (P-DHA) on breast cancer cell lines.
      Representative breast cancer cell lines, based on estrogen alpha receptor (ER)
      and oncogene Her-2 expression, were used and include MDA-MB-231 (ER-negative, Her
      2-negative), MCF-7 (ER-positive, Her-2-negative) AU565 (ER-negative, Her-2
      positive) and MDA-MB-361 (ER-positive, Her-2-positive). The PP-DHA conjugate
      significantly inhibited cell growth and induced cell loss in the breast cancer
      cell lines similarly; however, this conjugate was not effective against normal
      mammary epithelial cells. The effect of various conjugates were in PP-DHA>IPP
      DHA>DIPP-DHA>CHP-DHA>>P-DHA order. PP-DHA and IPP-DHA conjugates were stable in
      human and mouse serum. Furthermore, the non-hydrolyzable amide-linked conjugate
      analogues affected breast cancer cells in a manner similar to that of the ester
      linked conjugates. This suggests that ester-linked PP-DHA and IPP-DHA conjugates
      were stable during treatment to breast cancer cells due to structural hindrance.
      PP-DHA did not affect PPARalpha or PPARgamma activities but its anticancer
      effects appear to be mediated in part though the inhibition of histone
      deacetylase (HDAC) activity. Further experiments are needed to confirm their
      molecular target and to test the effectiveness of these compounds in an in vivo
      model for their anticancer properties. In conclusion, these results suggest that
      the novel PP-DHA and IPP-DHA conjugates and their amide derivatives may be useful
      for the treatment of breast cancer.

PMID- 20153204
TI  - Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA
      793887, a potent CDK inhibitor suitable for intravenous dosing.
AB  - We have recently reported CDK inhibitors based on the 6-substituted pyrrolo[3,4
      c]pyrazole core structure. Improvement of inhibitory potency against multiple
      CDKs, antiproliferative activity against cancer cell lines and optimization of
      the physico-chemical properties led to the identification of highly potent
      compounds. Compound 31 (PHA-793887) showed good efficacy in the human ovarian
      A2780, colon HCT-116 and pancreatic BX-PC3 carcinoma xenograft models and was
      well tolerated upon daily treatments by iv administration. It was identified as a
      drug candidate for clinical evaluation in patients with solid tumors.

PMID- 20153205
TI  - Bayesian statistical evaluation of peak area measurements in gamma spectrometry.
AB  - We analyze results from determinations of peak areas for a radioactive source
      containing several radionuclides. The statistical analysis was performed using
      Bayesian methods based on the usual Poisson model for observed counts. This model
      does not appear to be a very good assumption for the counting system under
      investigation, even though it is not questioned as a whole by the inferential
      procedures adopted. We conclude that, in order to avoid incorrect inferences on
      relevant quantities, one must proceed to a further study that allows us to
      include missing influence parameters and to select a model explaining the
      observed data much better.

PMID- 20153206
TI  - International exercise on 124Sb activity measurements.
AB  - An international exercise, registered as EUROMET project no. 907, was launched to
      measure both the activity of a solution of (124)Sb and the photon emission
      intensities of its decay. The same solution was sent by LNE-LNHB to eight
      participating laboratories. In order to identify possible biases, the
      participants were asked to use all possible activity measurement methods
      available in their laboratory and then to determine their reference value for
      comparison. Thus, measurement results from 4pibeta-gamma coincidence/anti
      coincidence counting, CIEMAT/NIST liquid-scintillation counting, 4pigamma
      counting with well-type ionization chambers and well-type crystal detectors were
      given. The results are compared and show a maximum discrepancy of about 1.6%:
      possible explanations are proposed.

PMID- 20153208
TI  - Electrical behavior of stored erythrocytes after exposure to gamma radiation and
      the role of alpha-lipoic acid as radioprotector.
AB  - The effects of gamma rays (25, 50 and 100 Gy) on stored erythrocytes were studied
      by measuring their dielectric properties and observing their morphology under
      scanning electron microscopy. Alpha lipoic acid (a potent natural antioxidant)
      was introduced prior to irradiation for radioprotection. It can be concluded that
      the dose level of 25 Gy can be considered a safe sterile dose; however,
      irradiation doses of 50 and 100 Gy should be applied with the addition of alpha
      acid to preserve the cell viability.

PMID- 20153207
TI  - Cationic technetium and rhenium complexes with pendant carbohydrates.
AB  - Three carbohydrate conjugated dipicolylamine chelators, 2-bis(2
      pyridinylmethyl)amino)ethyl 1-deoxy-1-thio-beta-D-glucopyranoside (L(1)), 2-bis(2
      pyridinylmethyl)amino)ethyl-beta-D-glucopyranoside (L(2)), and 2-bis(2
      pyridinylmethyl)amino)carboxamide-N-(2-amino-2-deoxy-D-glucopyranose) (L(3)) were
      complexed to the [M(CO)(3)](+) core (M=Tc, Re) and the properties of the
      resulting complexes were investigated. Synthesis and characterization of the
      chelator 2-bis(2-pyridinylmethyl)amino)ethyl 1-deoxy-1-thio-beta-D
      glucopyranoside (L(1)) and the corresponding Re complex are reported. All
      chelators were radiolabeled in high yield with [(99m)Tc(CO)(3)(H(2)O)(3)](+)
      (>98%) and [(186)Re(CO)(3)(H(2)O)(3)](+) (>80%). The chelators and Re-complexes
      were determined to not be substrates for the glucose metabolism enzyme
      hexokinase. However, the biodistribution of each of the (99m)Tc complexes
      demonstrated fast clearance from most background tissue, including >75% clearance
      of the activity in the kidneys and the liver within 2h post-injection.

PMID- 20153209
TI  - Valence-electron configuration of Ti and Ni in TixNi1-x alloys from Kbeta-to
      Kalpha X-ray intensity ratio studies.
AB  - Kbeta-to-Kalpha X-ray intensity ratios of Ti and Ni have been measured in pure
      metals and in alloys of Ti(x)Ni(1-x) (x=0.7, 0.6, 0.5, 0.4 and 0.3) following
      excitation by 22.69 keV X-rays from a 10 mCi (109)Cd radioactive point source.
      The valence-electron configurations of these metals were determined by
      corporation of measured Kbeta-to-Kalpha X-ray intensity ratios with the results
      of multiconfiguration Dirac-Fock calculation for various valence-electron
      configurations. Valence-electron configurations of 3d-transition metals in alloys
      indicate significant differences with respect to the pure metals. Our analysis
      indicates that these differences arise from delocalization and/or charge transfer
      phenomena in alloys. Namely, the observed change of the valence-electron
      configurations of metals in alloys can be explained with the transfer of 3d
      electrons from one element to the other element and/or the rearrangement of
      electrons between 3d and 4s, 4p states of individual metal atoms.

PMID- 20153211
TI  - Extraluminal cardiac paraganglioma: unexpected diagnosis of a large mediastinal
      mass.

PMID- 20153212
TI  - Left atrial isomerism: biventricular repair.
AB  - OBJECTIVE: Biventricular repair of hearts with left atrial isomerism often
      necessitates complex atrial and ventricular baffle procedures. We analysed our
      experience with an accent on baffle techniques. METHODS: From 1997 until 2008, 12
      patients (four male) with left atrial isomerism received biventricular repair.
      Their median age at surgery was 9 (range: 1-24) months. Four patients had
      dextrocardia. Nine patients presented with left superior vena cava, three with
      absent right superior vena cava, five with unroofed coronary sinus and nine
      others with inferior vena cava interruption with (hemi)azygos continuation.
      Anomalous pulmonary venous drainage was present in three patients. Eight had a
      monoatrium. Atrioventricular septal defect (AVSD) occurred in six (complete AVSD
      in two), One patient with complete AVSD had right pulmonary agenesia with long
      segment tracheal stenosis. Multiple VSDs presented in one whereas three patients
      had double-outlet right ventricle (DORV) (one with borderline LV hypoplasia). Two
      had previous pulmonary artery banding. Complex intra-atrial baffle constructions
      were performed in seven patients. Complete AVSDs were corrected using two patches
      and all other AVSDs had one patch repair. Multiple VSDs were closed directly.
      DORV patients had intraventricular tunnel repair. RESULTS: No early mortality
      occurred. Median follow-up was 54 (range: 2-134) months. One patient with
      complete AVSD and pulmonary agenesia died late after tracheal repair. Four
      patients needed five re-operations (closure of residual ASD (one), relief of left
      (two) or right (two) ventricular outflow obstruction, pulmonary artery branch
      plasty (one)). There was no atrial baffle stenosis. Four received a pacemaker.
      All survivors are in NYHA class I. CONCLUSIONS: Survival and functional status of
      left isomerism patients after biventricular repair is good. Complex repairs with
      atrial or ventricular baffles are frequent. Arrhythmias were common and pose a
      concern late after repair.

PMID- 20153213
TI  - Intramural coronary arteries and outcome of neonatal arterial switch operation.
AB  - OBJECTIVE: To evaluate the impact of coronary patterns with intramural arteries
      on the outcome of arterial switch operation (ASO) in neonates with transposition
      of the great arteries (TGA). METHODS: Between 1987 and 2008, 919 neonates
      underwent ASO for TGA. Forty-six (5.0%) had intramural coronary arteries.
      Intramural course involved the left main coronary artery in 28 of the 46 cases
      (61%), the left anterior descending artery in 12 patients (26%), the right
      coronary artery in three and both right and left coronary arteries in three
      cases. Various techniques were used to manage the coronary arteries: ASO without
      coronary relocation in one, ASO with coronary transfer as a single coronary
      button in nine and ASO with coronary transfer as two separate buttons in 36
      patients (additional pericardial patches were implanted to orientate the coronary
      button in nine cases or enlarge the coronary ostium in three cases). The
      intramural course was unroofed in most cases (after 1995). RESULTS: There were 13
      deaths (28%): two intra-operative, nine before discharge from the hospital and
      two after discharge; during the same period, overall mortality in the 873
      neonates with other coronary patterns was 3.9%. Actuarial survival at 10 years
      was 71 + or - 7%. Most deaths (11/13, i.e., 85%) were related to coronary
      complications. No time-trend effect was noted regarding mortality. Non-fatal
      coronary lesions were detected in eight patients (three with clinical evidence of
      myocardial infarction and five without). Five patients underwent re-operation for
      coronary revascularisation. Actuarial freedom from coronary events at 10 years
      was 46 + or - 10%. After a mean follow-up of 8.3 + or - 4.8 years, left
      ventricular function was normal in 97% of the survivors; minor ischaemic sequelae
      were present in two patients. CONCLUSIONS: Coronary patterns with intramural
      arteries remain associated with high coronary mortality and morbidity following
      neonatal ASO, even in the current era. The association of slit-like deformation
      of the ostium, stenosis of the intramural course and abnormal angle of take-off
      might explain the difficulty in coronary transfer. The technique of coronary
      transfer should be individually adapted to each anatomical situation. The place
      of patch ostioplasty of the intramural artery remains to be determined.

PMID- 20153214
TI  - Computed tomography-defined functional lung volume after segmentectomy versus
      lobectomy.
AB  - OBJECTIVE: Lung segmentectomy reduces the extent of resection required for
      lobectomy, but its resulting clinical benefits remain controversial. METHODS:
      Forty patients who underwent segmentectomy for stage I lung cancer over a 5-year
      period were matched to 40 patients who underwent lobectomy, using nearest
      available matching method with the estimated propensity score. We compared the
      functional volume of the ipsilateral lung to be resected, the ipsilateral lung to
      be preserved and the contralateral lung before, and 6 months after the operation,
      between the groups. Functional lung volume was defined as the lung volume
      representing normal attenuation (-600 to -910 Hounsfield units (HUs)) on computed
      tomography. We also compared the volumetric parameters to the spirometric
      parameters in 42 other patients, who underwent major lung resection for stage I
      lung cancer. RESULTS: We removed 11.6% of the functional lung volume by
      segmentectomy and 24.5% by lobectomy (P<0.001). However, the loss of the
      functional lung volume after segmentectomy was only 8.3% and that after lobectomy
      was 9.2%: this difference was not significant (P=0.7). Both the ipsilateral
      residual lung and the contralateral lung increased in functional volume more
      extensively after lobectomy than after segmentectomy. Increased postoperative
      functional lung volume was significantly correlated with improvement in
      postoperative pulmonary function (R=0.6, P<0.001). CONCLUSION: Although lung
      segmentectomy can reduce the extent of lung resection, it may not contribute to
      preserving postoperative functional lung volume because lobectomy promotes
      postoperative expansion of the bilateral residual lung, which compensates
      postoperative pulmonary functional loss to a greater extent than segmentectomy.

PMID- 20153215
TI  - Early operative mortality with tricuspid valve replacement does not simply depend
      on surgery itself; late-tricuspid regurgitation is a marker of late-stage
      myocardial and valvular heart disease.

PMID- 20153216
TI  - Randomised high- and low-dose heparin prophylaxis in patients undergoing
      thoracotomy for benign and malignant disease: effect on thrombo-elastography.
AB  - BACKGROUND: Both cancer patients and patients undergoing surgery are thought to
      be at an increased risk of thrombo-embolic events. Consequently, low-molecular
      weight heparin (LMWH) is administered to all such patients perioperatively. There
      is a lack of consensus in guidelines regarding the timing of administration and
      the dosage of thromboprophylactic agents. Studies have shown that thrombo
      elastography (TEG) is a useful test in assessing global haemostatic function, and
      has been validated in monitoring the dosage of LMWH. In this study, we assess the
      coagulation status of patients undergoing thoracic surgery with TEG, and the
      effectiveness of administered LMWH for thromboprophylaxis. METHODS: Thirty
      patients with primary lung cancer (LC) and 30 with benign lung disease (BL) were
      studied prospectively. Patients were randomised to receive subcutaneous LMWH 40
      mg once or twice per day perioperatively. Their coagulation status was monitored
      with TEG preoperatively and postoperatively for 3 consecutive days. RESULTS:
      Preoperative TEG parameters (k time, alpha angle and maximum amplitude (MA)) were
      within the normal range in both the LC and BL groups. Preoperative r time was
      prolonged in both the groups, but with no significant difference between the two
      groups (p>0.05). Postoperatively, r time was prolonged in some patients receiving
      LMWH twice daily, suggesting a possible adequate thromboprophylaxis in these
      patients only. CONCLUSION: This study demonstrates that the majority of patients
      with LC are not hypercoagulable. We also showed that LMWH once or twice a day
      might not provide sufficient thromboprophylaxis. We advocate screening for
      patients demonstrating hypercoagulable states and ensuring adequate
      thromboprophylaxis in this group of patients with careful monitoring.

PMID- 20153217
TI  - Spiroplasmas and phytoplasmas: microbes associated with plant hosts.
AB  - This review will focus on two distinct genera, Spiroplasma and 'Candidatus
      Phytoplasma,' within the class Mollicutes (which also includes the genus
      Mycoplasma, a concern for animal-based cell culture). As members of the
      Mollicutes, both are cell wall-less microbes which have a characteristic small
      size (1-2 microM in diameter) and small genome size (530 Kb-2220 Kb). These two
      genera contain microbes which have a dual host cycle in which they can replicate
      in their leafhopper or psyllid insect vectors as well as in the sieve tubes of
      their plant hosts. Major distinctions between the two genera are that most
      spiroplasmas are cultivable in nutrient rich media, possess a very characteristic
      helical morphology, and are motile, while the phytoplasmas remain recalcitrant to
      cultivation attempts to date and exhibit a pleiomorphic or filamentous shape.
      This review article will provide a historical over view of their discovery, a
      brief review of taxonomical characteristics, diversity, host interactions (with a
      focus on plant hosts), phylogeny, and current detection and elimination
      techniques.

PMID- 20153218
TI  - Cross comparison of rapid mycoplasma detection platforms.
AB  - The use of animal and plant derived raw materials in mammalian cell culture
      processes may provide a possible route of entry for adventitious contaminants
      such as mycoplasma. Mycoplasma contaminations of cell culture represent a serious
      challenge to the production of biotechnology derived therapeutics. The slow
      growing nature of mycoplasma can disguise their infection of cultures since cells
      may continue to proliferate, though at reduced levels and with lesser output of
      engineered protein. Rapid identification of mycoplasma contaminated cell cultures
      and materials enables a faster response time to prevent the spread of the
      contamination. We describe here the comparison of different mycoplasma detection
      methods: two nucleic acid-based technologies, the standard mycoplasma culture
      procedure, and a hybrid culture-quantitative PCR assay. In this study, a cell
      line infected with two species of mycoplasma was used to compare the different
      detection methods. Our data demonstrates that the two nucleic acid-based
      techniques are robust methods for detection of mycoplasma and have similar
      detection capability. In contrast, no mycoplasma was detected in the standard
      culture assay or in a hybrid culture-quantitative PCR assay. This shows a
      potential limitation of the culture assay that relies on the ability of
      mycoplasma to grow in broth media.

PMID- 20153219
TI  - The Ly49Q receptor plays a crucial role in neutrophil polarization and migration
      by regulating raft trafficking.
AB  - Neutrophils rapidly undergo polarization and directional movement to infiltrate
      the sites of infection and inflammation. Here, we show that an inhibitory MHC I
      receptor, Ly49Q, was crucial for the swift polarization of and tissue
      infiltration by neutrophils. During the steady state, Ly49Q inhibited neutrophil
      adhesion by preventing focal-complex formation, likely by inhibiting Src and PI3
      kinases. However, in the presence of inflammatory stimuli, Ly49Q mediated rapid
      neutrophil polarization and tissue infiltration in an ITIM-domain-dependent
      manner. These opposite functions appeared to be mediated by distinct use of
      effector phosphatase SHP-1 and SHP-2. Ly49Q-dependent polarization and migration
      were affected by Ly49Q regulation of membrane raft functions. We propose that
      Ly49Q is pivotal in switching neutrophils to their polarized morphology and rapid
      migration upon inflammation, through its spatiotemporal regulation of membrane
      rafts and raft-associated signaling molecules.

PMID- 20153220
TI  - Optimal germinal center responses require a multistage T cell:B cell adhesion
      process involving integrins, SLAM-associated protein, and CD84.
AB  - CD4(+) T cells deficient in signaling lymphocyte activation molecule (SLAM)
      associated protein (SAP) exhibit a selective impairment in adhesion to antigen
      presenting B cells but not dendritic cells (DCs), resulting in defective germinal
      center formation. However, the nature of this selective adhesion defect remained
      unclear. We found that whereas T cell:DC interactions were primarily integrin
      dependent, T cell:B cell interactions had both an early integrin-dependent phase
      and a sustained phase that also required SAP. We further found that the SLAM
      family member CD84 was required for prolonged T cell:B cell contact, optimal T
      follicular helper function, and germinal center formation in vivo. Moreover, both
      CD84 and another SLAM member, Ly108, mediated T cell adhesion and participated in
      stable T cell:B cell interactions in vitro. Our results reveal insight into the
      dynamic regulation of T cell:B cell interactions and identify SLAM family members
      as critical components of sustained T cell:B cell adhesion required for
      productive humoral immunity.

PMID- 20153222
TI  - Proper selection of patients for percutaneous embolo-sclerotherapy in patients
      with congenital vascular malformations (CVMs).
AB  - For the treatment of congenital vascular malformation (CVM), conservative,
      endovascular and/or surgical treatment have been sporadically attempted according
      to the type, location and clinical manifestations of the vascular lesions. At
      current practice, with no established treatment guidelines for CVM patients,
      there is much room for ineffective interventions and occurrence of complications
      related with the treatment. Therefore, it is important to select proper
      candidates for the endovascular or surgical treatment in CVM patients to avoid
      ineffective treatment and its complications and to obtain better treatment
      results. We describe the basic considerations before the selection of candidates
      for percutaneous embolo-sclerotherapy in patients with CVM based on our own
      experiences at a specialised CVM clinic.

PMID- 20153223
TI  - Stem cell therapy in PAD.
AB  - Critical limb ischemia (CLI) continues to form a substantial burden on Western
      health care. Despite recent advances in surgical and radiological vascular
      techniques, a large number of patients is not eligible for these
      revascularisation procedures and faces amputation as their ultimate treatment
      option. Growth factor therapy and stem cell therapy - both therapies focussing on
      augmenting postnatal neovascularisation - have raised much interest in the past
      decade. Based on initial pre-clinical and clinical results, both therapies appear
      to be promising strategies to augment neovascularisation and to reduce symptoms
      and possibly prevent amputation in CLI patients. However, the underlying
      mechanisms of postnatal neovascularisation are still incompletely understood.
      Both fundamental research as well as large randomised trials are needed for
      further optimisation of these treatment options, and will hopefully lead to
      needed advances in the treatment of no-option CLI patients in the near future.

PMID- 20153221
TI  - CD95-ligand on peripheral myeloid cells activates Syk kinase to trigger their
      recruitment to the inflammatory site.
AB  - Injury to the central nervous system initiates an uncontrolled inflammatory
      response that results in both tissue repair and destruction. Here, we showed
      that, in rodents and humans, injury to the spinal cord triggered surface
      expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L
      stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and
      metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase,
      ultimately leading to increased migration. Exclusive CD95L deletion in myeloid
      cells greatly decreased the number of neutrophils and macrophages infiltrating
      the injured spinal cord or the inflamed peritoneum after thioglycollate
      injection. Importantly, deletion of myeloid CD95L, but not of CD95 on neural
      cells, led to functional recovery of spinal injured animals. Our results indicate
      that CD95L acts on peripheral myeloid cells to induce tissue damage. Thus,
      neutralization of CD95L should be considered as a means to create a controlled
      beneficial inflammatory response.

PMID- 20153224
TI  - The education system to master endovascular aortic repair in Japan - the Japanese
      Committee for Stentgraft Management.
AB  - OBJECTIVE: The Japanese Committee for Stentgraft Management (JACSM) was
      established with the aim of ensuring the safe and proper reach of commercial
      stent grafts following their regulatory approval. This study examines the
      validity of the practice standards developed by JACSM. METHODS: JACSM comprises
      10 associations related to endovascular treatment. Based on the practice
      standards developed by JACSM, the status of practising institutions, practising
      surgeons, supervising surgeons and the results of follow-up surveys were
      analysed. RESULTS: In the 2.5 years following the establishment of JACSM, 298
      institutions have fulfilled the practice standards. The number of practising
      surgeons reached 493, and the number of supervising surgeons reached 177. There
      were 3089 registered cases up to June 2009. The present study analysed 1570 cases
      registered in the 2 years from July 2006 to June 2008. The hospital mortality
      rate was low (0.4%) in the follow-up surveys. CONCLUSIONS: Early results
      following the introduction of stent grafts were generally good. The procedure
      spread safely without the learning curve seen in the initial stages following
      introduction of new medical materials, indicating that the practice standards
      were appropriate.

PMID- 20153225
TI  - Why pyridine containing pyrido[2,3-d]pyrimidin-7-ones selectively inhibit CDK4
      than CDK2: insights from molecular dynamics simulation.
AB  - Designing selective cyclin-dependent kinase 4 (CDK4) inhibitors is an area of
      intense research to develop potential anticancer drugs. The molecular basis
      governing the selective inhibition of CDK4 by lig17 (6-bromo-8-cyclopentyl-2-(5
      piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one) has been
      investigated using molecular dynamics simulation. The positive charge on the
      ligand was determined to be an important contributor for CDK4 selectivity due to
      the electronegative nature of its active site. Similar studies on CDK2 indicated
      that Lys89 intrudes into the active site displacing the positive charge on lig17
      away from the active center. This intrusion was observed to propel a drastic
      conformational change in lig17, weakening its binding interactions with the
      protein. The pyridine nitrogen (N(AR)) of lig17 was capable of interacting with
      His95 (CDK4) through hydrogen bonding. N(AR) also showed a strong tendency to
      mediate protein-ligand interactions through a bridged water molecule, only when
      bound to CDK4. The G-loop of CDK4 was observed to fluctuate extensively when
      complexed with lig17 and a novel "flipping-out" mechanism exhibited by
      Tyr17(CDK4/CDK4-17) is reported in this study. Although these proteins have
      similar folds, the results from principal component analysis (PCA) indicate that
      CDK4 and CDK2 follow an anti-correlated behavior towards the accessibility of the
      active site.

PMID- 20153226
TI  - A comprehensive structure-activity analysis of protein kinase B-alpha (Akt1)
      inhibitors.
AB  - Protein kinase B (PKB, also known as Akt) belongs to the AGC subfamily of the
      protein kinase superfamily. Akt1 has been reported as a central player in
      regulation of metabolism, cell survival, motility, transcription and cell-cycle
      progression, among the signalling proteins that respond to a large variety of
      signals. In this study an attempt was made to understand structural requirements
      for Akt1 inhibition using conventional QSAR, k-nearest neighbour QSAR and novel
      GQSAR methods. With this intention, a wide variety of structurally diverse Akt1
      inhibitors were collected from various literature reports. The conventional QSAR
      analyses revealed the key role of Baumann's alignment independent topological
      descriptors along with other descriptors such as the number of hydrogen bond
      acceptors, hydrogen bond donors, rotatable bonds and aromatic oxygen (SaaOcount)
      along with molecular branching (chi3Cluster), alkene carbon atom type (SdsCHE
      index) in governing activity variation. Further, the GQSAR analyses show that
      chemical variations like presence of hetero-aromatic ring, flexibility, polar
      surface area and fragment length present in the hinge binding fragment (in the
      present case fragment D) are highly influential for achieving highly potent Akt1
      inhibitors. In addition, this study resulted in a k-nearest neighbour
      classification model with three descriptors suggesting the key role of oxygen
      (SssOE-index) and aromatic carbon (SaaCHE-index and SaasCE-index) atoms electro
      topological environment that differentiate molecules binding to Akt1 kinase or PH
      domain. The developed models are interpretable, with good statistical and
      predictive significance, and can be used for guiding ligand modification for the
      development of potential new Akt1 inhibitors.

PMID- 20153227
TI  - [Ezetimibe: caution in the face of doubt].

PMID- 20153228
TI  - [Clinical pathway for women with locally advanced breast cancer and neoadjuvant
      chemotherapy].
AB  - Breast cancer is a very important public health issue, due its high incidence and
      mortality. Neoadjuvant chemotherapy has proven to be a valid option in the
      treatment of operable breast cancer and a better aesthetic result if breast-
      tumour ratio is unfavourable. The administration of the therapy itself is
      complicated, but the difficulty lies mainly in the management of side effects or
      adverse effects of the treatment. The emergence of a new therapeutic applications
      need to be constantly reviewed, which combined with the high work loads in the
      oncology day hospital requires easily managed, standardised and updated
      methodologies. A method of choice would be the use of clinical pathways that are
      just emerging in Spain, but could be helpful in managing this disease. The aim of
      this publication is to share the design of a clinical path for this specific
      disease with the scientific community. The process of preparing this document has
      been work of reflection, literature review and unification of criteria that may
      be used to facilitate work within the Oncology Day Hospital, improving the
      records of the work involved, especially those related to nursing practice. Their
      evaluation would enable proposals to be defined for improving and facilitating
      evidence-based practice.

PMID- 20153230
TI  - [Profile of adolescents with social withdrawal admitted to a partial
      hospitalization unit of Mental Health].
AB  - OBJECTIVE: To analyse the general characteristics of teenagers admitted to the
      Day Care Unit who fulfilled the criteria of social withdrawal, in order to
      implement a specific action plan within the existing resources for adolescents.
      METHOD: In this retrospective descriptive observational study, data were
      collected from withdrawal adolescent teenagers admitted to the unit over the year
      2008. The data analysed were personal variables, diagnostic assessment on
      discharge, IQ assessment and Scale for Assessment of Communication and
      Interaction Skills and truancy. RESULTS: Of the 76 adolescents admitted to the
      unit, a total of 33 teenagers with social isolation were included in this study
      (43%). They had an average age of 15 years, an equal distribution between sexes
      and with a stay in the Unit 33 days longer than the general population studied.
      The average intellectual quotient of the social isolation group did not exceed
      the lower zone of the Weschler Scale (<80), and they scored below 50 points in
      the Scale for Assessment of Communication and Interaction Skills. CONCLUSIONS:
      The present research has enabled us to quantify the withdrawal phenomenon and
      some of its characteristics in a sample of adolescents admitted to the unit, in
      order to develop an interdisciplinary treatment program that allows us to address
      social withdrawal using a more holistic and effective approach.

PMID- 20153231
TI  - [Fibrinolysis in acute myocardial infarction in the emergency department of a
      general hospital].

PMID- 20153232
TI  - [Confidence, supervision and taking responsibility: changes in the development of
      autonomy in families who live with an adolescent with cystic fibrosis].
AB  - OBJECTIVE: A growing number of families with an adolescent who has cystic
      fibrosis can now envisage their child making the transition from adolescence to
      adulthood. Limited research has been conducted to date regarding the nature of
      the interactions between adolescents and their parents during the development of
      the adolescent's independence. METHOD: The aim of this qualitative case study was
      to explore the experience of families with an adolescent who has cystic fibrosis,
      at the pre-transfer stage from a paediatric clinic to adult care. A systemic
      framework was used to get a better understanding of this phenomenon. Semi
      directed interviews with seven families were conducted and a content analysis was
      performed. RESULTS: Features of the development of autonomy are characterised by
      three dimensions of the parental experience: (a) confidence that must be
      established between the adolescent and the parent, (b) adolescent's gradual
      increase of responsibility and (c) parent's supervision of the adolescent.
      CONCLUSIONS: This study gives new information on parental experience as regards
      the development of autonomy in adolescents who have cystic fibrosis. The results
      underline the importance of taking parental experience into consideration in
      order to support families in the development of the adolescent's autonomy.

PMID- 20153233
TI  - Clinical features of Malaysian children hospitalized with community-acquired
      seasonal influenza.
AB  - OBJECTIVES: The clinical impact of seasonal influenza is understudied in tropical
      countries. The aim of this study was to describe the clinical features and
      seasonal pattern of influenza in children hospitalized in Malaysia, and to
      identify predictors of severe disease. METHODS: Children hospitalized with
      community-acquired, laboratory-confirmed influenza at a teaching hospital in
      Kuala Lumpur, Malaysia during 2002-2007 were identified retrospectively. Clinical
      data were collected, and predictors of severe disease were identified by
      multivariate logistic regression. All influenza cases from 1982 to 2007 were also
      analyzed for seasonal patterns. RESULTS: A total of 132 children were included in
      the study, 48 (36.4%) of whom had underlying medical conditions. The mean age was
      2.5 years and 116 (87.9%) were <5 years old. The most common presenting features
      were fever or history of fever, cough, rhinitis, vomiting, and pharyngitis.
      Severe influenza was seen in 16 patients (12.1%; nine previously healthy),
      including 12 (9.1%; eight previously healthy) requiring intensive care. There
      were three (2.3%) deaths. Severe disease was associated with age <12 months,
      female sex, and absence of rhinitis on admission. Influenza was seen year-round,
      with peaks in November-January and May-July. CONCLUSIONS: Seasonal influenza has
      a considerable impact on children hospitalized in Malaysia, in both the healthy
      and those with underlying medical conditions.

PMID- 20153234
TI  - Endocarditis due to Gram-negative bacteria.

PMID- 20153235
TI  - Treatment of benign bone tumours of the hand using osteoscopy.
AB  - Curettage and bone grafting are used traditionally to treat benign bone tumours
      of the hand. Some authors are proposing minimally invasive treatment using
      endoscopy. Our purpose is to standardise this technique based on a study of the
      number and locations of entry points. This is a report on three benign metacarpal
      bone tumours treated with three different endoscopic approaches: multiportal,
      extended uniportal and oblique uniportal. In theory, the multiportal approach has
      several drawbacks: weakening of the bone cortex, a limited visual field and
      seepage of injectable phosphocalcic cement. The extended uniportal approach
      causes cortical defects, unacceptable in a minimally invasive technique. The
      oblique uniportal approach seems less troublesome; vision of the bone cavity is
      good, curettage of the tumour is complete, the bone cortex is undamaged and there
      is no leakage of injectable phosphocalcic cement. All things considered, the
      oblique osteoscopic uniportal approach seems to be the best option for the
      management of benign bone tumours of the hand.

PMID- 20153236
TI  - Large scale environmental applications of high power ultrasound.
AB  - In the present work, the use of high power ultrasound as a process tool for the
      removal of persistent organic pollutants (POPs) from soil and the treatment of
      bauxite red mud waste from the Bayer process is discussed. Laboratory scale
      experiments have confirmed that the application of high power ultrasound to
      slurries of contaminated soil and of bauxite ore can treat two major
      environmental problems cost-effectively. Destruction rates of POPs in soil of 90%
      and higher have been achieved whereas 85% iron oxide has been extracted from red
      mud waste leaving a low-iron fraction of approximately 50% by weight which is
      more environmentally friendly. A 4x4 kW pilot plant capable of treating 2.5
      tonnes of slurry per day has been commissioned to provide more accurate estimates
      of power and energy requirements to allow scale-up to industrial use.

PMID- 20153237
TI  - Inertial Gait Phase Detection for control of a drop foot stimulator Inertial
      sensing for gait phase detection.
AB  - An Inertial Gait Phase Detection system was developed to replace heel switches
      and footswitches currently being used for the triggering of drop foot
      stimulators. A series of four algorithms utilising accelerometers and gyroscopes
      individually and in combination were tested and initial results are shown.
      Sensors were positioned on the outside of the upper shank. Tests were performed
      on data gathered from a subject, sufferer of stroke, implanted with a drop foot
      stimulator and triggered with the current trigger, the heel switch. Data tested
      includes a variety of activities representing everyday life. Flat surface
      walking, rough terrain and carpet walking show 100% detection and the ability of
      the algorithms to ignore non-gait events such as weight shifts. Timing analysis
      is performed against the current triggering method, the heel switch. After
      evaluating the heel switch timing against a reference system, namely the Vicon
      370 marker and force plates system. Initial results show a close correlation
      between the current trigger detection and the inertial sensor based triggering
      algorithms. Algorithms were tested for stairs up and stairs down. Best results
      are observed for algorithms using gyroscope data. Algorithms were designed using
      threshold techniques for lowest possible computational load and with least
      possible sensor components to minimize power requirements and to allow for
      potential future implantation of sensor system.

PMID- 20153238
TI  - Probable REM sleep behaviour disorder and STN-DBS outcome in Parkinson's Disease.
AB  - OBJECTIVE: To assess whether the presence of probable REM sleep behaviour
      disorder (pRBD) influences the long-term outcome of Parkinson's Disease (PD)
      patients undergoing Subthalamic Nucleus Deep Brain Stimulation (STN-DBS).
      BACKGROUND: RBD is a parasomnia characterized by loss of muscular atonia and
      complex motor behaviours during REM sleep, frequently reported in PD patients.
      Recent evidence suggests that RBD is associated with akinetic rigid disease type
      and increased frequency of falls. We wondered whether the presence of RBD would
      also influence the long-term outcome of STN-DBS. METHODS: Forty-one consecutive
      PD patients treated with bilateral STN-DBS were assessed. The diagnosis of pRBD
      was based on a clinical interview investigating the occurrence of diagnostic
      criteria for RBD. The Unified Parkinson's Disease Rating Scale was used to
      compare the on- and off-medication conditions preoperatively and the on
      stimulation/on- and off-medication conditions 1 and 3 years postoperatively. The
      general linear model for multivariate measures was used to analyse the
      interaction of pRBD with STN-DBS outcome measures. RESULTS: pRBD was present in
      12 out of 41 patients (29%) undergoing STN-DBS. Patients with pRBD had a
      significantly poorer outcome three years after STN-DBS compared to patients
      without pRBD, in particular for axial symptoms. CONCLUSIONS: Our findings suggest
      that the presence of pRBD in PD patients undergoing STN-DBS may be associated
      with a less favourable outcome and a more prominent development of axial symptoms
      over time.

PMID- 20153239
TI  - Transnational health and treatment networks: meaning, value and place in health
      seeking amongst southern African migrants in London.
AB  - Drawing upon research undertaken with migrants from southern Africa living in
      London, this paper examines the important role played by transnational health
      networks in influencing individual's treatment seeking decisions. As well as
      exploring the ways in which these networks provide important sources of help and
      support for people in times of ill health, the paper examines the ways in which
      treatments from particular places and contexts carry certain associations,
      meanings and values, which are in turn, considered vital in influencing health
      care outcomes.

PMID- 20153240
TI  - The evolution of parasitism in plants.
AB  - The multiple independent origins of plant parasitism suggest that numerous
      ancestral plant lineages possessed the developmental flexibility to meet the
      requirements of a parasitic life style, including such adaptations as the ability
      to recognize host plants, form an invasive haustorium, and regulate the transfer
      of nutrients and other molecules between two different plants. In this review, we
      focus on the Orobanchaceae, which are unique among the parasitic plants in that
      extant member species include the full range of host dependence from facultative
      to obligate parasites. The recent emergence of genomic resources for these plants
      should provide new insights into parasitic plant evolution and enable the
      development of novel genetic strategies for controlling parasitic weeds.

PMID- 20153241
TI  - Advances in imaging RNA in plants.
AB  - Increasing evidence shows that many RNAs are targeted to specific locations
      within cells, and that RNA-processing pathways occur in association with specific
      subcellular structures. Compartmentation of mRNA translation and RNA processing
      helps to assemble large RNA-protein complexes, while RNA targeting allows local
      protein synthesis and the asymmetric distribution of transcripts during cell
      polarisation. In plants, intercellular RNA trafficking also plays an additional
      role in plant development and pathogen defence. Methods that allow the
      visualisation of RNA sequences within a cellular context, and preferably at
      subcellular resolution, can help to answer important questions in plant cell and
      developmental biology. Here, we summarise the approaches currently available for
      localising RNA in vivo and address the specific limitations inherent with plant
      systems.

PMID- 20153242
TI  - Towards a neural basis of music-evoked emotions.
AB  - Music is capable of evoking exceptionally strong emotions and of reliably
      affecting the mood of individuals. Functional neuroimaging and lesion studies
      show that music-evoked emotions can modulate activity in virtually all limbic and
      paralimbic brain structures. These structures are crucially involved in the
      initiation, generation, detection, maintenance, regulation and termination of
      emotions that have survival value for the individual and the species. Therefore,
      at least some music-evoked emotions involve the very core of evolutionarily
      adaptive neuroaffective mechanisms. Because dysfunctions in these structures are
      related to emotional disorders, a better understanding of music-evoked emotions
      and their neural correlates can lead to a more systematic and effective use of
      music in therapy.

PMID- 20153244
TI  - Hybrid sterility in plant: stories from rice.
AB  - Hybrid sterility is the most common form of postzygotic reproductive isolation in
      plants. The best-known example is perhaps the hybrid sterility between indica and
      japonica subspecies of Asian cultivated rice (Oryza sativa L.). Major progress
      has been reported recently in rice in identifying and cloning hybrid sterility
      genes at two loci regulating female and male fertility, respectively. Genetic
      analyses and molecular characterization of these genes, together with the results
      from other model organisms especially Drosophila, have advanced the understanding
      of the processes underlying reproductive isolation and speciation. These findings
      also have significant implications for crop genetic improvement, by providing the
      feasibility and strategies for overcoming intersubspecific hybrid sterility thus
      allowing the development of intersubspecific hybrids.

PMID- 20153243
TI  - High expression of excision repair cross-complementation group 1 protein predicts
      poor outcome in patients with nasopharyngeal cancer.
AB  - We evaluated the prognostic significance of excision repair cross-complementation
      group 1 protein (ERCC1) and thymidylate synthase (TS) in patients with
      nasopharyngeal cancer (NPC) treated with concurrent chemoradiotherapy (CCRT). Pre
      treatment tumor biopsy specimens from 41 patients with locally advanced NPC
      (stage I: 1, II: 10, III: 9, IV: 21 patients) were analyzed for ERCC1 and TS
      expression by immunohistochemistry. All patients were treated with one cycle of
      induction chemotherapy (5-fluorouracil 1000 mg/m(2)/day and cisplatin
      20mg/m(2)/day, days 1-4) followed by CCRT starting on day 22. CCRT consisted of
      radiotherapy (70 Gy/35 fractions for 7 weeks) with cisplatin 20mg/m(2)/day for 4
      days on weeks 1, 4, and 7 of radiotherapy. High expression of ERCC1 and TS was
      observed in 25 (60%) and 21 (51%) patients, respectively. High expression of
      ERCC1 was associated with WHO type 1 or 2 histology (p=0.045). With a median
      follow-up duration of 106 months (32-152 months) in survivors, the 5-year overall
      survival (OS) of all patients was 53%. In univariate analysis, 5-year OS (73%
      versus 39%, p=0.005) was significantly inferior in patients with high expression
      of ERCC1, while high expression of TS was not correlated with patient outcome. In
      multivariate analysis, high expression of ERCC1 was a significant independent
      prognostic factor for poor OS (p=0.029) along with WHO type 1 or 2 histology.
      High expression of ERCC1 protein may be a useful prognostic factor for poor
      outcome in patients with locally advanced NPC treated with CCRT.

PMID- 20153245
TI  - Grounding information security in healthcare.
AB  - PURPOSE: The objective of this paper is to show that grounded theory (GT),
      together with mixed methods, can be used to involve healthcare professionals in
      the design and enhancement of access control policies to Electronic Medical
      Record (EMR) systems. METHODS: The mixed methods applied for this research
      included, in this sequence, focus groups (main qualitative method that used
      grounded theory for the data analysis) and structured questionnaires (secondary
      quantitative method). RESULTS: Results showed that the presented methodology can
      be used to involve healthcare professionals in the definition of access control
      policies to EMR systems and explore these issues in a diversified and integrated
      way. The methodology allowed for the generation of great amounts of data in the
      beginning of the study and in a short time span. Results from the applied
      methodology revealed a first glimpse of the theories to be generated and
      integrated, with future research, into access control policies. CONCLUSIONS: The
      methodological research described in this paper is very rarely, if ever, applied
      in developing security tools such as access control. Nevertheless, it can be an
      effective way of involving healthcare professionals in the definition and
      enhancement of access control policies and in making information security more
      grounded into their workflows and daily practices.

PMID- 20153246
TI  - Enhanced spinal excitation from ankle flexors to knee extensors during walking in
      stroke patients.
AB  - OBJECTIVES: It is still unclear to what an extent altered reflex activity
      contributes to gait deficit following stroke. Spinal group I and group II
      excitations from ankle dorsiflexors to knee extensors were investigated during
      post-stroke walking. METHODS: Electrical stimulation was applied to the common
      peroneal nerve (CPN) in the early stance, and the short-latency biphasic
      excitation in Quadriceps motoneurones was evaluated from the Vastus Lateralis
      (VL) rectified and averaged (N=50) EMG activity in 14 stroke patients walking at
      0.6-1.6 km/h, and 14 control subjects walking at 3.2-4.8 and at 1 km/h. RESULTS:
      The second peak of the CPN-induced biphasic facilitation in VL EMG activity,
      which is likely mediated by group II excitatory pathways, was larger on the
      paretic side of the patients, as compared to their nonparetic side or control
      subjects, whatever their walking speed. CONCLUSIONS: The spinal, presumed group
      II, excitation from ankle dorsiflexors to knee extensors is particularly enhanced
      during post-stroke walking probably due to plastic adaptations in the descending
      control. SIGNIFICANCE: This adaptation may help to stabilize the knee in early
      stance when the patients have recover ankle dorsiflexor functions.

PMID- 20153247
TI  - The effect of subacute denervation on the electrical anisotropy of skeletal
      muscle: implications for clinical diagnostic testing.
AB  - OBJECTIVE: Applied electrical current flows preferentially along rather than
      across muscle fibers, a characteristic called anisotropy. In this study, we
      investigate the alteration in muscle anisotropy after denervation. METHODS: Eight
      adult male rats underwent sciatic nerve crush and the gastrocnemius was harvested
      from 1 to 2.5 weeks later. Muscle from 12 additional healthy rats was also
      obtained. Multifrequency electrical impedance measurements were made on the
      tissue and its conductivity and relative permittivity (i.e., its polarizability)
      calculated. Anisotropy of the tissue was determined by calculating conductivity
      and permittivity differences, subtracting transverse from longitudinal values.
      Muscle fiber and blood vessel quantification were also performed. RESULTS: The
      mean conductivity difference for sciatic crush animals was higher (p<0.05) than
      for the healthy animals across the frequency spectrum, due to a greater increase
      in longitudinal conductivity than in transverse conductivity. For example, at 10
      kHz, the conductivity difference was 0.15S/m for healthy animals and 0.29 S/m for
      post-crush animals. Relative permittivity difference values, however, were
      similar between groups. There was a strong correlation of conductivity anisotropy
      to muscle fiber size but not to blood vessel area. CONCLUSIONS: Anisotropy of
      muscle conductivity increases markedly after subacute denervation injury.
      SIGNIFICANCE: This alteration in anisotropy has direct relevance to the clinical
      application of electrical impedance myography. We also speculate that it may
      impact other forms of diagnostic testing, including needle electromyography and
      magnetic resonance imaging.

PMID- 20153248
TI  - Spinal DC stimulation in humans modulates post-activation depression of the H
      reflex depending on current polarity.
AB  - OBJECTIVE: Transcranial direct current stimulation induces long-lasting changes
      in cortical excitability in humans depending on the current used. Further,
      transcutaneous spinal application of direct current (tsDCS) induces plastic
      changes in spinal conduction properties, tested by somatosensory evoked
      potentials. To verify this thesis on plastic changes in spinal circuitry, we
      investigated the effects of tsDCS on H-reflex size and post-activation
      depression. METHODS: Ten healthy subjects participated in the study. The
      H(max)/M(max) ratio and H-reflex post-activation depression were evaluated
      before, at current offset, and 15 min after anodal, cathodal or sham tsDCS.
      Stimulation of the spinal cord (2.5 mA, 0.063 mA/cm(2), 0.056 C/cm(2)) was
      applied for 15 min at Th11 level. RESULTS: Anodal tsDCS induced a lasting
      decrease in H-reflex post-activation depression, while cathodal stimulation
      resulted in a sustained increase. Sham stimulation had no significant effects.
      The H(max)/M(max) ratio remained unchanged throughout all conditions. CONCLUSION:
      Anodal and cathodal tsDCS is a non-invasive and painless method that is able to
      induce lasting changes in the efficacy of the Ia fibre-motoneurone synapse.
      SIGNIFICANCE: Transcutaneous spinal DC stimulation might be a valuable new tool
      in modulating spinal motor pathways.

PMID- 20153249
TI  - Identification of the epileptogenic zone in patients with tuberous sclerosis:
      concordance of interictal and ictal epileptiform activity.
AB  - OBJECTIVE: In the majority of patients with tuberous sclerosis complex (TSC)
      multifocal epileptiform activity is present interictally. Therefore, its value in
      identifying epilepsy surgery candidates has been doubted. We hypothesize that
      dominant interictal epileptiform foci are concordant with the ictal onset zone in
      TSC patients. METHODS: Consistency and dominance of focal interictal epileptiform
      activity was assessed in 19 patients with a clinical definite diagnosis of TSC.
      The ictal onset zone was identified. Concordance between interictal en ictal
      findings was analyzed. If concordance was found epilepsy surgery was proposed.
      RESULTS: We found dominant, consistently present, focal interictal epileptiform
      activity in 14 of the 19 patients. Concordance between the dominant interictal
      focus and the ictal onset zone was found in 11 of the 14 patients (79%). In one
      patient the ictal onset zone could not be identified and discordance was present
      in two patients. Epilepsy surgery was performed in six patients rendering three
      of them seizure free, and one had a seizure reduction >90%. In these patients
      local concordance was found whereas regional concordance was found in the two
      patients who did not benefit from epilepsy surgery. CONCLUSIONS: A dominant as
      well as a consistent interictal focus is concordant with the ictal onset zone in
      the majority of TSC patients. SIGNIFICANCE: Future studies of TSC patients
      addressing the value of interictal foci in the consideration of epilepsy surgery,
      in absence of clear ictal onset zone, are necessary.

PMID- 20153250
TI  - Evaluation of the therapeutic effect of theta burst stimulation on drug-resistant
      auditory hallucinations in a schizophrenic patient and its impact on cognitive
      function and neuronal excitability: a case study.

PMID- 20153251
TI  - Genotoxicity evaluation in workers occupationally exposed to lead.
AB  - Lead (Pb) is a widely used heavy metal with a broad industrial usage.
      Nevertheless, Pb is a serious public health issue as it is one of the most
      widespread environmental and industrial toxins. The aim of this investigation was
      to assess the genotoxicity of Pb using the comet assay, micronucleus (MN) and
      chromosomal aberrations (CA) test. Blood and urinary Pb content, levels of delta
      aminolevulinic acid dehydratase in the erythrocytes (E-ALAD) and delta
      aminolevulinic acid in urine (U-ALA) were determined. The exposure associated
      oxidative stress was also studied. The study group comprised of 90 male Pb
      recovery unit workers and 90 matched controls. The results indicated that the
      exposed workers had a significantly higher mean comet tail length than that of
      controls (P<0.05). Analysis of micronuclei in buccal epithelial cells (BEC's) and
      peripheral blood lymphocytes (PBL) revealed that there was a significant increase
      in frequency of MN in exposed subjects than controls. The frequency of aberrant
      metaphases was also found to be significantly elevated in the Pb exposed workers.
      The levels of antioxidant enzymes were relatively reduced (P>0.05) while the rate
      of lipid peroxidation was higher in the exposed subjects. Blood and urinary Pb
      concentrations were found to be higher in exposed workers than in controls. E
      ALAD levels were reduced and U-ALA levels were elevated in the exposed subjects
      in comparison to controls. Results of analysis, taking the confounding factors
      into consideration provide evidence for the association of Pb exposure and
      genotoxicity, and predict the increased risk of cancer to the exposed workers. In
      view of the observed results, it can be strongly concluded that the workers
      comprise the risk group and adequate safety, precautionary and preventive
      measures could only minimize exposure and the related health hazards.

PMID- 20153252
TI  - Recognising the diversity of the athletes and activity participants we work with.

PMID- 20153253
TI  - The immunobiology of aluminium adjuvants: how do they really work?
AB  - Aluminium adjuvants potentiate the immune response, thereby ensuring the potency
      and efficacy of typically sparingly available antigen. Their concomitant critical
      importance in mass vaccination programmes may have prompted recent intense
      interest in understanding how they work and their safety. Progress in these areas
      is stymied, however, by a lack of accessible knowledge pertaining to the
      bioinorganic chemistry of aluminium adjuvants, and, consequently, the
      inappropriate application and interpretation of experimental models of their mode
      of action. The objective herein is, therefore, to identify the many ways that
      aluminium chemistry contributes to the wide and versatile armoury of its
      adjuvants, such that future research might be guided towards a fuller
      understanding of their role in human vaccinations.

PMID- 20153254
TI  - Crosstalk pathways between Toll-like receptors and the complement system.
AB  - The Toll-like receptors (TLRs) and complement are key innate defense systems that
      are triggered rapidly upon infection. Although both systems have been
      investigated primarily as separate entities, an emerging body of evidence
      indicates extensive crosstalk between complement and TLR signaling pathways.
      Analysis of these data suggests that the complement-TLR interplay reinforces
      innate immunity or regulates excessive inflammation, through synergistic or
      antagonistic interactions, respectively. However, the facility of complement and
      TLRs for communication is exploited by certain pathogens as a means to modify the
      host response in ways that favor the persistence of the pathogens. Further
      elucidation of regulatory links between complement and TLRs is essential for
      understanding their complex roles in health and disease.

PMID- 20153255
TI  - Change and the NHS workforce: ambivalence, anxiety and anger.

PMID- 20153256
TI  - Human ovarian tissue cryopreservation: quality of follicles as a criteria of
      effectiveness.
AB  - Experiments comparing vitrification and conventional freezing of mammalian
      ovarian tissue show that vitrification can also guarantee the storage of viable
      follicles after warming, but conventional freezing is more effective. The central
      goal of cryotechnology is the preservation of intact follicles. This article
      presents a critical opinion about the normality of follicles after vitrification
      of human ovarian tissue and microbial contamination as a result of direct contact
      of this tissue with liquid nitrogen at vitrification.

PMID- 20153257
TI  - Impact of epispadias repair on bladder growth in boys with classic bladder
      exstrophy.
AB  - OBJECTIVE: Growth of the bladder in children with bladder exstrophy is primarily
      responsible for later ability to void continently. Improvement in bladder
      capacity has been noted in some boys following epispadias repair. Does the timing
      of epispadias repair influence the ability of the bladder to grow? METHODS: Data
      were collected regarding bladder volume measurements, obtained under anesthesia
      using a standard technique, during yearly follow-up of boys with classic bladder
      exstrophy. Volume prior to epispadias repair was compared to the next volume
      measure following repair. Timing of epispadias repair was compared to changes in
      bladder capacity in 30 boys. Monthly increases in bladder capacity were
      calculated in boys repaired at <12 (4), 13-24 (12) and 25-48 (14) months.
      RESULTS: Patients who had surgery prior to 12 months of age had the highest rate
      of monthly increase in bladder capacity (2.40 cc/month). Monthly growth rates
      were 1.91 cc/month for patients repaired at 13-24 months and 1.18 cc/month for
      those repaired at 25-48 months. CONCLUSIONS: Epispadias repair does lead to early
      increase in bladder capacity in boys with classic bladder exstrophy. The monthly
      increases in bladder capacity are greater in boys <12 months. Improvement in
      bladder volume is less likely when epispadias is repaired after age 29 months.

PMID- 20153258
TI  - 46,XY pure gonadal dysgenesis: clinical presentations and management of the tumor
      risk.
AB  - PATIENTS: Eleven patients with 46,XY PGD were divided into two groups. Six
      symptomatic girls (group 1) were referred for amenorrhea (n = 3), gonadal tumor
      (n = 2) or campomelic dysplasia (n = 1). Five asymptomatic screened patients
      (group 2) were diagnosed as 46,XY PGD after familial investigation of the two
      probands with gonadal tumor. Bilateral gonadectomy was performed in all patients.
      RESULTS: In group 1, pathologic examination revealed an association of
      dysgerminoma with gonadoblastoma (n = 2), bilateral gonadoblastoma (n = 2) and
      streak gonads (n = 2). Prophylactic gonadectomy in asymptomatic patients (group
      2) also showed asymptomatic dysgerminoma with gonadoblastoma (n = 1), bilateral
      gonadoblastoma (n = 2) and streak gonads (n = 2). CONCLUSIONS: A gonadal tumor
      arising in a girl with pubertal delay may be related to dysgenesis of the gonad.
      Primary amenorrhea or diagnosis of dysgerminoma should warrant karyotype, and
      familial study if 46,XY PGD is found. Considering the high incidence of
      gonadoblastoma and the early occurrence of dysgerminoma, early bilateral
      gonadectomy is recommended.

PMID- 20153260
TI  - Behavioral deficit and decreased GABA receptor functional regulation in the
      cerebellum of epileptic rats: effect of Bacopa monnieri and bacoside A.
AB  - In the present study, the effects of Bacopa monnieri and its active component,
      bacoside A, on motor deficit and alterations of GABA receptor functional
      regulation in the cerebellum of epileptic rats were investigated. Scatchard
      analysis of [(3)H]GABA and [(3)H]bicuculline in the cerebellum of epileptic rats
      revealed a significant decrease in B(max) compared with control. Real-time
      polymerase chain reaction amplification of GABA(A) receptor subunits
      GABA(Aalpha1), GABA(Aalpha5,) and GABA(Adelta)-was downregulated (P<0.001) in the
      cerebellum of epileptic rats compared with control rats. Epileptic rats exhibit
      deficits in radial arm and Y-maze performance. Treatment with B. monnieri and
      bacoside A reversed these changes to near-control levels. Our results suggest
      that changes in GABAergic activity, motor learning, and memory deficit are
      induced by the occurrence of repetitive seizures. Treatment with B. monnieri and
      bacoside A prevents the occurrence of seizures thereby reducing the impairment of
      GABAergic activity, motor learning, and memory deficit.

PMID- 20153259
TI  - Monocytes differentiated with IL-15 support Th17 and Th1 responses to wheat
      gliadin: implications for celiac disease.
AB  - Interleukin (IL)-15 contributes to the immunopathogenesis of Celiac disease (CD).
      However, it is not clear how IL-15 affects APC that shape adaptive immune
      responses to the dietary antigen, gliadin. Using PBMC from healthy individuals,
      we show that monocytes differentiated with IL-15 (IL15-DC) produced IL-1beta, IL
      6, IL-15, IL-23, TNFalpha and CCL20 in response to pepsin-trypsin digested
      gliadin (PTG) and activated contact-dependent Th17 and Th1 responses from
      autologous CD4(+) T cells. Lower concentrations of IL-15 augmented IFNgamma
      responses to PTG in PBMC from CD patients compared to controls. Thus, IL-15
      supports Th17 and Th1 responses to a dietary antigen that is normally well
      tolerated in healthy individuals by generating IL15-DC. These potentially
      pathogenic immune responses may result in CD patients and not healthy individuals
      as a consequence of IL-15 hypersensitivity. Therefore, genetic and/or
      environmental factors that control IL-15 expression and responsiveness in the
      intestine likely participate in the pathogenesis of CD.

PMID- 20153261
TI  - The neurobiological substrates of behavioral manifestations during temporal lobe
      seizures: a neuroethological and ictal SPECT correlation study.
AB  - Ictal behavior coupled with SPECT findings during 28 seizures in patients with
      temporal lobe epilepsy (TLE) with unilateral hippocampal sclerosis (13 left; 15
      right) was displayed as flowcharts from right-sided (RTLE) plus left-sided (LTLE)
      seizures. Ictal SPECT was classified blind to neuroethology. Behaviors were
      categorized as ipsilateral to the epileptogenic zone (IL), contralateral to the
      epileptogenic zone (CL), or bilateral. SPECT intensity and region were
      categorized as IL or CL to the epileptogenic zone. All patients developed
      automatisms and had hyperperfusion in their temporal lobes. Patients' verbal
      responses to questions had statistical interactions in RTLE but not in LTLE sum.
      Most CL dystonic posturing was correlated to IL basal ganglia hyperperfusion.
      Basal ganglia activation occurred in seizures without dystonic posturing and CL
      manual automatisms, and lack of IL dystonic posturing and the presence of CL
      cerebellar hemispheric hyperperfusion were also observed. Coupling of
      neuroethology and SPECT findings reliably evaluates ictal behavior and
      functionality of associated brain areas.

PMID- 20153262
TI  - RNF8-dependent histone modifications regulate nucleosome removal during
      spermatogenesis.
AB  - During spermatogenesis, global nucleosome removal occurs where histones are
      initially replaced by transition proteins and subsequently by protamines. This
      chromatin reorganization is thought to facilitate the compaction of the paternal
      genome into the sperm head and to protect the DNA from damaging agents. Histone
      ubiquitination has been suggested to be important for sex chromosome inactivation
      during meiotic prophase and nucleosome removal at postmeiotic stages. However,
      the mechanisms regulating these ubiquitin-mediated processes are unknown. In this
      study, we investigate the role of the ubiquitin ligase RNF8 during
      spermatogenesis and find that RNF8-deficient mice are proficient in meiotic sex
      chromosome inactivation (MSCI) but deficient in global nucleosome removal.
      Moreover, we show that RNF8-dependent histone ubiquitination induces H4K16
      acetylation, which may be an initial step in nucleosome removal. Thus, our
      results show that RNF8 plays an important role during spermatogenesis through
      histone ubiquitination, resulting in trans-histone acetylation and global
      nucleosome removal.

PMID- 20153263
TI  - A higher-order complex containing AF4 and ENL family proteins with P-TEFb
      facilitates oncogenic and physiologic MLL-dependent transcription.
AB  - AF4 and ENL family proteins are frequently fused with MLL, and they comprise a
      higher order complex (designated AEP) containing the P-TEFb transcription
      elongation factor. Here, we show that AEP is normally recruited to MLL-target
      chromatin to facilitate transcription. In contrast, MLL oncoproteins fused with
      AEP components constitutively form MLL/AEP hybrid complexes to cause sustained
      target gene expression, which leads to transformation of hematopoietic
      progenitors. Furthermore, MLL-AF6, an MLL fusion with a cytoplasmic protein, does
      not form such hybrid complexes, but nevertheless constitutively recruits AEP to
      target chromatin via unknown alternative mechanisms. Thus, AEP recruitment is an
      integral part of both physiological and pathological MLL-dependent
      transcriptional pathways. Bypass of its normal recruitment mechanisms is the
      strategy most frequently used by MLL oncoproteins.

PMID- 20153264
TI  - Postimplant rectal dosimetry is not dependent on 103Pd or 125I seed activity.
AB  - PURPOSE: In this study, the effect of prostate brachytherapy seed activity on
      postimplant rectal dosimetry was evaluated in Pro-Qura (Prostate Brachytherapy
      Quality Assurance; Seattle, WA) proctored, community-based programs. METHODS AND
      MATERIALS: Twenty-three hundred patients (1563 iodine-125 [(125)I] and 737
      palladium-103 [(103)Pd]) from 78 brachytherapists with postimplant rectal
      dosimetry were identified. Seed activity was stratified into three tertiles for
      each isotope (<=0.300, 0.301-0.326, and >0.326 mCi/seed for (125)I and <=1.330,
      1.331-1.547, and >1.547 mCi/seed for (103)Pd). Postimplant dosimetry was
      performed in a standardized fashion. The rectum was contoured by outlining the
      outer rectal wall. The volume of the rectum receiving 100% of the prescription
      dose (R(100)) was calculated in cubic centimeters. The prostate V(100) and D(90)
      volumes were also calculated. RESULTS: The mean prostate volume was 35.8 and 32.3
      cm(3) for (125)I and (103)Pd. The median time to postimplant CT was 30 days. For
      (125)I, the V(100) increased from 91.0% to 93.7% (p=0.012) and the D(90)
      increased from 105.9% to 108.7% (p<0.001) for the lowest to the highest (125)I
      seed activities. In contrast, no significant changes in V(100) (p=0.751) or D(90)
      (p=0.200) were discerned when stratified by seed activity. For both isotopes,
      there was no correlation between seed activity and R(100), and R(100) was highest
      for the intermediate seed activities. Overall, the R(100) was lower for (103)Pd
      vs. (125)I (0.63 vs. 0.82 cm(3), p<0.001). CONCLUSIONS: Within the confines of
      seed activities used in this study, higher activity seeds did not result in a
      deleterious effect on rectal dose. Higher activity seeds were associated with
      improved prostate dosimetry for (125)I, whereas (103)Pd dosimetry was not
      dependent on seed activity.

PMID- 20153265
TI  - J wave syndromes.
AB  - The J wave, also referred to as an Osborn wave, is a deflection immediately
      following the QRS complex of the surface ECG. When partially buried in the R
      wave, the J wave appears as J-point elevation or ST-segment elevation. Several
      lines of evidence have suggested that arrhythmias associated with an early
      repolarization pattern in the inferior or mid to lateral precordial leads,
      Brugada syndrome, or arrhythmias associated with hypothermia and the acute phase
      of ST-segment elevation myocardial infarction are mechanistically linked to
      abnormalities in the manifestation of the transient outward current (I(to))
      mediated J wave. Although Brugada syndrome and early repolarization syndrome
      differ with respect to the magnitude and lead location of abnormal J-wave
      manifestation, they can be considered to represent a continuous spectrum of
      phenotypic expression that we propose be termed J-wave syndromes. This review
      summarizes our current state of knowledge concerning J-wave syndromes, bridging
      basic and clinical aspects. We propose to divide early repolarization syndrome
      into three subtypes: type 1, which displays an early repolarization pattern
      predominantly in the lateral precordial leads, is prevalent among healthy male
      athletes and is rarely seen in ventricular fibrillation survivors; type 2, which
      displays an early repolarization pattern predominantly in the inferior or
      inferolateral leads, is associated with a higher level of risk; and type 3, which
      displays an early repolarization pattern globally in the inferior, lateral, and
      right precordial leads, is associated with the highest level of risk for
      development of malignant arrhythmias and is often associated with ventricular
      fibrillation storms.

PMID- 20153266
TI  - Role of inflammation and oxidative stress in atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia seen in
      clinical practice. Increasing evidence indicates that inflammation and oxidative
      stress contribute to the pathogenesis of AF, but their role remains poorly
      defined. In addition, whether inflammation and oxidative stress are associated
      with particular types of AF is unclear. OBJECTIVE: The purpose of this study was
      to define the role of inflammation and oxidative stress in AF. METHODS: Using a
      case-control study design, 305 patients with AF were compared with 150 control
      patients. AF was categorized into lone and typical AF and further subcategorized
      as paroxysmal, persistent, or permanent AF. Serum concentrations of interleukin
      (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant
      protein (MCP)-1, vascular endothelial growth factor (VEGF), N-terminal pro-brain
      (B-type) natriuretic peptide (NTpBNP), and urinary F(2)-isoprostanes, a measure
      of oxidative stress, were measured. RESULTS: IL-6, IL-8, IL-10, TNF-alpha, MCP1,
      VEGF, and NTpBNP concentrations were independently associated with AF (all P
      <.05). However, F(2)-isoprostane excretion was not elevated (P = .50). Graded
      increases in TNF-alpha [median (interquartile range) 6.8 (3.4-11.3), 8.0 (5.6
      10.9), 10.1 (5.7-12.4) pg/mL, P <.05] and NTpBNP [170.6 (67.3-481.9), 681.39
      (310.3-1,439.0), 1,179.9 (653.1-2,096.0) pg/mL, P <.001] were seen among the
      subgroups of paroxysmal, persistent, and permanent AF, respectively. CONCLUSION:
      Inflammatory biomarkers were significantly increased in patients with AF,
      supporting a strong association between inflammation and AF. Surprisingly,
      urinary F(2)-isoprostanes, a sensitive index of systemic oxidative stress in
      vivo, were not increased in AF overall or in different subtypes of AF.

PMID- 20153267
TI  - Sympathetic preganglionic neurons project to superior cervical ganglion via C7
      spinal nerve in pup but not in adult rats.
AB  - We investigated the distribution of sympathetic preganglionic fibers in each
      spinal nerve of the brachial plexus, and its correlation with presence of
      Horner's syndrome in the pup and adult rats. According to surgical intervention
      to the C7-T1 spinal nerves in the right side, rats of 7 days postnatal (P7), P14
      and adulthood (24 for each age group) were subdivided into four subgroups of six
      each, respectively, i.e., C7 or C8 or T1 spared subgroup--where C7 or C8 or T1
      alone was kept intact with avulsion of the other two spinal nerves and division
      of the sympathetic chain caudal to the stellate ganglion; C7-T1 avulsed subgroup-
      where C7-T1 were all avulsed but the sympathetic chain kept intact. Fluoro-Gold
      (FG) was injected bilaterally into the superior cervical ganglion (SCG) for
      labeling of sympathetic preganglionic neurons (SPNs). Furthermore, Horner's
      syndrome was examined after avulsion of different spinal nerves for P14 and adult
      rats. In C7 spared subgroups, FG-labeled neurons accounted averagely for 16.9% in
      P7, 13.5 in P14 and 1.0 in adult rats, and difference was statistically
      significant between P7 and adults (Z=-2.9, P=0.004), P14 and adults (Z=-2.9,
      P=0.004). When both C7 and C8 were avulsed, Horner's syndrome was more prone to
      be produced in pups than in adults (chi(2)=4.2, P=0.04). These results indicate
      that some SPNs project to SCG via C7 in the pup, but this pathway disappears
      during postnatal development. It suggests that in newborns with brachial
      plexopathy, presence of Horner's syndrome may be correlated with avulsion of C7.

PMID- 20153268
TI  - Somatic genome variations interact with environment, genome and epigenome in the
      determination of the phenotype: A paradigm shift in genomics?

PMID- 20153269
TI  - Beyond postural drainage and percussion: Airway clearance in people with cystic
      fibrosis.
AB  - BACKGROUND: Evidence indicates that there are no statistically significant
      differences in effectiveness among the airway clearance techniques (ACTs) of
      active cycle of breathing, autogenic drainage, positive expiratory pressure (PEP)
      or oscillating PEP in the short-term, but are there differences in the long-term
      (one year)? The objective of the study was to demonstrate non-inferiority in the
      long-term. METHODS: Seventy-five people with cystic fibrosis entered the
      prospective, randomised controlled trial of these five different ACTs. The
      primary outcome measure was forced expiratory volume in one second (FEV(1)).
      Secondary outcome measures included exercise capacity and health related quality
      of life. RESULTS: Using intention to treat, data were available on 65 subjects at
      the end of the study period. There were no statistically significant differences
      among the regimens in the primary outcome measurement of FEV(1) (p=0.35).
      CONCLUSION: In different countries either one or several airway clearance
      regimens are used. This study provides evidence in support of current practices.

PMID- 20153270
TI  - Simultaneous quantitative determination of olmesartan and hydrochlorothiazide in
      human plasma and urine by liquid chromatography coupled to tandem mass
      spectrometry.
AB  - A specific, sensitive and rapid method based on high performance liquid
      chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was developed for
      the simultaneous determination of olmesartan (OLM) and hydrochlorothiazide (HCTZ)
      in human plasma and urine. Solid-phase extraction (SPE) was used to isolate the
      analytes from biological matrices followed by injection of the extracts onto a
      C(18) column with isocratic elution. Detection was carried out on a triple
      quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode
      using negative electrospray ionization (ESI). The method was validated over the
      concentration range of 1.00-1000 ng/mL and 5.00-5000 ng/mL for OLM in human
      plasma and urine as well as 0.500-200 ng/mL and 25.0-25,000 ng/mL for HCTZ in
      human plasma and urine, respectively. Inter- and intra-run precision of OLM and
      HCTZ were less than 15% and the accuracy was within 85-115% for both plasma and
      urine. The average extraction recoveries were 96.6% and 92.7% for OLM, and 87.2%
      and 72.1% for HCTZ in human plasma and urine, respectively. The linearity,
      recovery, matrix effect and stability were validated for OLM/HCTZ in human plasma
      and urine.

PMID- 20153271
TI  - Charlemagne was very tall, but not robust.
AB  - The left tibia of Charlemagne, the Medieval "Father of Europe" has been X-rayed
      and CT scanned to determine his still highly debated stature. We found the
      healthy bone to be long (430 mm) but rather not robust (total mid-shaft cross
      sectional area 473 mm(2), cortical area 352 mm(2)). Reconstructed stature of 1.84
      m falls at about 99% of Medieval heights, which would be ca. 1.95 m in present
      day Europe. Thus, tall stature indeed could have contributed to the success of
      "Charles the Great" as a king emperor and soldier.

PMID- 20153272
TI  - [Hospital admissions due to whooping cough: experience of the del nino hospital
      in Panama. Period 2001-2008].
AB  - INTRODUCTION: Bordetella pertussis (whooping cough) is a worldwide public health
      problem. It is estimated that there are about 20 to 40 million cases with 200,000
      400,000 deaths and is increasing in infants and adults. MATERIALS AND METHODS: An
      observational, retrospective study was made. We reviewed the epidemiologic
      surveillance notification forms from 2001 to 2008 period at the Epidemiology
      Department of Hospital Del Nino, a tertiary paediatric reference centre in Panama
      City. All pertussis (whooping cough) cases confirmed by PCR and cultures were
      selected. RESULTS: From a total of 759 notifications of suspected whooping cough
      cases, 180 confirmed cases using PCR and culture were analyzed for this study.
      The admission rate in all ages was 14.4/10,000 admissions, predominantly in < or
      =3 months with 42.76/10,000 admissions and which accounted for 75% of the cases.
      Cough was the most important symptom (91%). Cyanosis, leucocytosis and
      lymphocytosis were the most characteristic clinical findings when comparing
      positive pertussis with negative. More than two thirds of the subjects less than
      3 months of age had not been vaccinated at the time of admission. The death rate
      was 8.3%, more than half of them in subjects less than 1 month of age.
      CONCLUSIONS: Whooping cough is an important public health problem. Post-partum
      vaccination could be a strategy to reduce morbidity and mortality in infants less
      than 3 months of age.

PMID- 20153273
TI  - [Vitamin A deficiency and nutritional status in patients with Down's syndrome].
AB  - INTRODUCTION: Vitamin A deficiency (VAD) is a worldwide public health problem.
      Epidemiological studies of VAD prevalence have been conducted in individuals with
      chromosome load and genetic potential compared with the general population;
      however, there are few studies in patients with Down's syndrome (DS). The
      objective of this study was to determine the prevalence of VAD and analyse
      nutritional status in patients with DS. METHODS: A prospective and cross
      sectional study was performed, with 50 karyotypically normal (KN) individuals
      (10.4+/-3.7 years old) and 38 randomly selected patients with DS (8.2+/-4.1 years
      old). Serum retinol was determined by HPLC using the Bieri method, with an
      international reference standard to define VAD (serum retinol <20 microg/dL). The
      data were analysed using the SAS/STAT statistical program. RESULTS: The
      prevalence of VAD was 18.4% in individuals with DS and 4% in KN individuals (OR:
      5.42; 95% CI=0.93-40.64; p=0.02). Children with DS between two and six years old
      shown a significativily lower serum retinol (p=<0.05).The patients with DS also
      showed a significant decrease in height and weight compared to KN (p=<0.001).
      CONCLUSIONS: The prevalence of VAD detected in patients with DS could be
      considered a public health problem. Also, the chromosome 21 trisomy represent a
      risk factor associated with VAD.

PMID- 20153274
TI  - [3D-CT in the diagnosis of craniosynostosis].

PMID- 20153275
TI  - Use of Dermabond as a dressing for prominent ear correction: a sound alternative
      to head dressings.

PMID- 20153276
TI  - A rare complication after septoplasty procedure in a misdiagnosed submucous cleft
      palate case: palatal fistula.
AB  - Nasal septoplasty is a common and low-risk procedure performed very frequently in
      plastic surgery as well as in otorhinolaryngology. The development of a palatal
      perforation following a nasal septoplasty procedure is a very rare event with
      only a few cases reported in the literature. A patient with palatal fistula
      formation after septoplasty procedure is presented here, who was later on
      diagnosed with submucous cleft palate during the repair of the palatal fistula.

PMID- 20153277
TI  - Management of an unfortunate triad after breast reconstruction: pyoderma
      gangrenosum, full-thickness chest wall defect and Acinetobacter Baumannii
      Infection.
AB  - If diagnosed late, post-surgical pyoderma gangrenosum (PSPG) is a rare, tricky
      and potentially life-threatening complication. Once diagnosed, immunosuppressive
      agents may provoke further complications. Well-intentioned extensive serial
      debridement may cause deep skin and soft-tissue defects, requiring skin grafting
      and possible flap surgery. The combination of necessary immunosuppressive
      treatment, protracted hospital stay and broad-spectrum systemic antimicrobial
      therapy may encourage serious acquired multidrug resistance (MDR). We report an
      unfortunate triad following breast reconstruction of PSPG, full-thickness chest
      wall defect and MDR with Acinetobacter baumannii infection. Interdisciplinary
      treatment using free flap surgery and negative-pressure wound therapy with
      instillation therapy (V.A.C.Instill(R) Wound Therapy) enabled survival and
      complete wound closure.

PMID- 20153278
TI  - Supratrochlear artery based V-Y flap for partial eyebrow reconstruction.

PMID- 20153279
TI  - Treatment of genu recurvatum in hemiparetic adult patients: a systematic
      literature review.
AB  - INTRODUCTION AND METHODS: We carried out a systematic review of the literature on
      treatment of genu recurvatum in hemiparetic adult patients by searching the
      PubMed, Pedro, Trip Database and Science Direct databases. The following keywords
      were used: (recurvatum or hyperextension or knee) and (hemiplegia or
      hemiparesis). RESULTS: Nine articles met our selection criteria. Four assessed
      retraining methods (functional electric stimulation or electrogoniometric
      feedback), two assessed orthopaedic or neurosurgical treatments and three
      articles focused on orthoses. DISCUSSION AND CONCLUSION: Even though all the
      various treatments produced encouraging results, most of the reviewed studies
      presented methodological limitations. Moreover, none of the selected articles
      suggested a treatment strategy which takes account of the various aetiologies in
      genu recurvatum. On the basis of some of the reviewed articles and our own
      clinical experience, we propose an aetiology-specific treatment strategy for genu
      recurvatum patients. In a broad patient population, this categorization could
      form the basis for testing the specificity of each treatment method as a function
      of the cause of genu recurvatum. This approach could help confirm the clinical
      indications and identify the most appropriate treatment for each patient.

PMID- 20153280
TI  - Effects of running retraining after knee anterior cruciate ligament
      reconstruction.
AB  - OBJECTIVE: The aim of this study was to analyze the effect of running retraining
      on the recovery of the knee's functional and muscular properties after anterior
      cruciate ligament (ACL) reconstruction. METHODS: Eighty-five athletes who had
      undergone ACL reconstruction surgery were selected randomly to receive, or not to
      receive, controlled running training based on interval training and speed
      exercises. The effect of retraining was measured by the evolution of the knee's
      isokinetic strength deficit and progress (at angular speeds of 60 and 180 degrees
      /s), the knee laxity parameters and the score on the Lysholm Knee Scale from the
      4th to the 6th month after the surgery. Forty subjects were retrained and
      compared with 40 control-group subjects. The effect of the retraining program was
      studied in terms of the type of ACL reconstruction and the effect of time.
      RESULTS: After retraining, no difference was found for isokinetic knee strength
      deficit and progress, knee laxity and Lysholm Knee Score. The isokinetic strength
      deficit was influenced mainly by the type of ACL reconstruction. CONCLUSION: It
      would seem that running retraining has an insufficient effect on the muscular and
      functional recovery after ACL reconstruction, despite the fact that this type of
      training is well-tolerated.

PMID- 20153281
TI  - Influence of maxillary cortical bone thickness, implant design and implant
      diameter on stress around implants: a three-dimensional finite element analysis.
AB  - PURPOSE: There is no clear evidence of the factors that could improve implant
      biomechanics in the posterior maxilla. Thus, a finite element analysis was
      performed to investigate the effect of maxillary cortical bone thickness, implant
      design and diameter on stress around implants. METHODS: A total of 12 models of
      the posterior maxilla with implant were computer-simulated by varying the
      thickness of the alveolar cortical bone (1.5, 1.0, 0.5 or 0 mm) and implant
      characteristics (cylindrical implant of 4.1-mm diameter, screw-type implants of
      4.1-mm or 4.8-mm outer diameters). On top of each implant, forces were separately
      applied axially (100 N) and buccolingually (50 N), and the von Mises stresses
      were calculated. RESULTS: Regardless of load direction, implant design and
      diameter, cortical and cancellous bone stresses increased with the decrease of
      crestal cortical bone thickness. In the absence of crestal cortical bone,
      cancellous bone stresses were highest and, under axial load, were transferred to
      the sinus floor. Implant design and diameter influenced stress to a less extent,
      especially under buccolingual load and in the presence of crestal cortical bone.
      CONCLUSIONS: From a biomechanical viewpoint, to improve implant success odds in
      the posterior maxilla, rather than implant selection, careful preoperative
      evaluation of the cortical bone at the planned implant site is recommended. If
      this cortical bone is very thin or even lacking, implant treatment should be
      carried on with caution by progressive loading in the range of functional loads.

PMID- 20153282
TI  - Enhanced infection of liver sinusoidal endothelial cells in a mouse model of
      antibody-induced severe dengue disease.
AB  - Dengue virus (DENV) causes disease ranging from dengue fever (DF), a self-limited
      febrile illness, to the potentially lethal dengue hemorrhagic fever and dengue
      shock syndrome (DHF/DSS). DHF/DSS usually occurs in patients who have acquired
      DENV-reactive antibodies prior to infection, either from a previous infection
      with a heterologous DENV serotype or from an immune mother. Hence, it has been
      hypothesized that subneutralizing levels of antibodies exacerbate disease, a
      phenomenon termed antibody-dependent enhancement (ADE). However, given the lack
      of suitable animal models for DENV infection, the mechanism of ADE and its
      contribution to pathology remain elusive. Here we demonstrate in mice that DENV
      specific antibodies can sufficiently increase severity of disease so that a
      mostly nonlethal illness becomes a fatal disease resembling human DHF/DSS.
      Antibodies promote massive infection of liver sinusoidal endothelial cells
      (LSECs), resulting in increased systemic levels of virus. Thus, a subprotective
      humoral response may, under some circumstances, have pathological consequences.

PMID- 20153283
TI  - Finding of Parastrongylus cantonensis (Chen, 1935) in Rattus rattus in Tenerife,
      Canary Islands (Spain).
AB  - Parastrongylus cantonensis is a parasite of murid rodents that can infect humans
      and cause health problems as eosinophilic meningitis. Although it is endemic in
      south Asia, the Pacific islands, Australia, USA, and a few Caribbean islands, it
      has been extended to new geographical regions. In the Canary Islands (Spain) a
      survey of helminths of Rattus rattus, Rattus norvegicus and Mus musculus
      domesticus was carried out. Furthermore, five species of molluscs were examined
      for nematode larvae to determine whether they are potential intermediate hosts of
      P. cantonensis. Nematodes were found in the lungs of 15% of 67 R. rattus examined
      in Tenerife, one of the four studied islands, with a prevalence of 20% in the
      highest focus of infection. Based on morphological and molecular analysis, with
      the complete internal transcribed spacer 2 (ITS-2) and a fragment of the small
      subunit ribosomal RNA (SSU rRNA) nucleotide sequences, nematodes were identified
      as P. cantonensis. Larval nematodes found from snails and slugs were identified
      as third-stage (L(3)) Metastrongyloidea, but the molecular study showed that they
      did not belong to P. cantonensis. This is the first finding of angiostrongyliasis
      in rats in the Canary Islands (Spain). New molecular data for this species and
      Parastrongylus dujardini are reported. The presence of P. cantonensis in Tenerife
      could be of importance from the public health point of view. Further studies are
      required in order to look for other potential foci of infections in the Canary
      Islands.

PMID- 20153284
TI  - A review on Anopheles subpictus Grassi--a biological vector.
AB  - Anopheles subpictus is a complex of four isomorphic sibling species A, B, C and D
      and is recognized as a primary vector of malaria, a disease of great socio
      economic importance, in Australasian Zone, Celebes, Portuguese Timor and South
      East Asia and a secondary vector in Sri Lanka. This species is also a vector of
      some helminth and arboviruses. This species has been reported so far from
      nineteen countries of the Oriental and Australasian Zones. An. subpictus complex
      is the most abundant anopheline in most parts of the Indian subcontinent, with a
      widespread distribution eastwards and southwards to Papua New Guinea, westwards
      to Iran and northwards to China. Resistance to insecticide is alarming in many
      parts of the world. Different aspects of this important mosquito species
      including attempts related to its control have been discussed which will be
      highly useful to carry out further research.

PMID- 20153285
TI  - The ethics of improving African traditional medical practice: a response.

PMID- 20153286
TI  - Selection of reference genes for quantitative real-time reverse transcription
      polymerase chain reaction in concanavalin A-induced hepatitis model.
AB  - Quantitative real-time reverse transcription-polymerase chain reaction (Q-PCR)
      has become an indispensable technique for accurate determination of gene
      expression in various samples. In mice, intravenous injection of concanavalin A
      (ConA) leads to acute hepatitis and liver injury. Functional studies based on
      this model have provided insights for understanding the mechanisms of liver
      injury. However, no data have been reported to validate reference genes during
      the progression of ConA-induced hepatitis (CIH). In this study, IkappaBalpha and
      C/EBPbeta messenger RNA (mRNA) levels were examined using Q-PCR with ACTB as the
      reference gene after ConA injection. However, we got inconsistent results with
      previous reports determining IkappaBalpha and C/EBPbeta mRNA expression levels.
      The results indicate the necessity for stability analysis of candidate reference
      genes in the CIH model. geNorm, NormFinder, and BestKeeper software analysis
      indicates that ACTB is the most unstable gene during CIH progression among the 10
      reference genes tested, whereas RPLP0 or HPRT1 is the most stable one. This study
      demonstrates that some of the commonly used reference genes are inadequate for
      normalization of Q-PCR data due to their expression instability. Furthermore,
      this study validates HPRT1 and RPLP0 as appropriate reference genes for Q-PCR
      analysis in the CIH model.

PMID- 20153287
TI  - Holocarboxylase synthetase: correlation of protein localisation with biological
      function.
AB  - Holocarboxylase synthetase (HCS) governs the cellular fate of the essential
      micronutrient biotin (Vitamin H or B7). HCS is responsible for attaching biotin
      onto the biotin-dependent enzymes that reside in the cytoplasm and mitochondria.
      Evidence for an alternative role, viz the regulation of gene expression, has also
      been reported. Recent immunohistochemical studies reported HCS is primarily
      nuclear, inconsistent with the location of HCS activity. Improved understanding
      of biotin biology demands greater knowledge about HCS. Here, we investigated the
      localisation of HCS and its isoforms. Three variants were observed that differ at
      the N-terminus. All HCS isoforms were predominantly non-nuclear, consistent with
      the distribution of biotin protein ligase activity. Unlike the longer constructs,
      the Met(58) isoform was also detected in the nucleus--a novel observation
      suggesting shuttling activity between nucleus and cytoplasm. We resolved that the
      previous controversies in the literature are due to specificity and detection
      limitations that arise when using partially purified antibodies.

PMID- 20153288
TI  - Size-dependent neurotoxicity of beta-amyloid oligomers.
AB  - The link between the size of soluble amyloid beta (Abeta) oligomers and their
      toxicity to rat cerebellar granule cells (CGC) was investigated. Variation in
      conditions during in vitro oligomerization of Abeta(1-42) resulted in peptide
      assemblies with different particle size as measured by atomic force microscopy
      and confirmed by dynamic light scattering and fluorescence correlation
      spectroscopy. Small oligomers of Abeta(1-42) with a mean particle z-height of 1-2
      nm exhibited propensity to bind to phospholipid vesicles and they were the most
      toxic species that induced rapid neuronal necrosis at submicromolar
      concentrations whereas the bigger aggregates (z-height above 4-5 nm) did not bind
      vesicles and did not cause detectable neuronal death. A similar neurotoxic
      pattern was also observed in primary cultures of cortex neurons whereas Abeta(1
      42) oligomers, monomers and fibrils were non-toxic to glial cells in CGC cultures
      or macrophage J774 cells. However, both oligomeric forms of Abeta(1-42) induced
      reduction of neuronal cell densities in the CGC cultures.

PMID- 20153289
TI  - Stearoyl-CoA desaturase and insulin signaling--what is the molecular switch?
AB  - Increasing evidence suggests that stearoyl-CoA desaturase (SCD), the rate
      limiting enzyme of monounsaturated fatty acid biosynthesis, is an important
      factor in the pathogenesis of lipid-induced insulin resistance. Mice with a
      targeted disruption of the SCD1 gene have improved glucose tolerance compared to
      wild-type mice, despite lower fasting plasma insulin levels. Increased SCD
      activity has been found in insulin-resistant humans and animals, whereas SCD1
      deficiency attenuates both diet- and genetically-induced impairment of insulin
      action. Phosphorylation of serine and threonine residues on insulin receptor,
      insulin receptor substrates (IRS1 and IRS2), and on Akt has been shown to be the
      major step in insulin signaling that is altered due to the lack of SCD1. In this
      review we discuss perturbations in cell signaling and lipid metabolism cascades
      in insulin-sensitive tissues due to SCD1 deficiency. In particular, we address
      the role of cellular signaling molecules including free fatty acids, ceramides,
      fatty acyl-CoAs, AMP-activated protein kinase, protein tyrosine phosphatase 1B as
      well as of membrane fluidity. While the precise mechanism of SCD action on
      insulin signaling remains to be clarified, current findings on SCD point to a
      very promising novel target for the treatment of insulin resistance.

PMID- 20153291
TI  - Role of FtsH2 in the repair of Photosystem II in mutants of the cyanobacterium
      Synechocystis PCC 6803 with impaired assembly or stability of the CaMn(4)
      cluster.
AB  - The FtsH2 protease, encoded by the slr0228 gene, plays a key role in the
      selective degradation of photodamaged D1 protein during the repair of Photosystem
      II (PSII) in the cyanobacterium Synechocystis sp. PCC 6803. To test whether
      additional proteases might be involved in D1 degradation during high rates of
      photodamage, we have studied the synthesis and degradation of the D1 protein in
      DeltaPsbO and DeltaPsbV mutants, in which the CaMn(4) cluster catalyzing oxygen
      evolution is less stable, and in the D1 processing mutants, D1-S345P and
      DeltaCtpA, which are unable to assemble a functional cluster. All four mutants
      exhibited a dramatically increased rate of D1 degradation in high light compared
      to the wild-type. Additional inactivation of the ftsH2 gene slowed the rate of D1
      degradation dramatically and increased the level of PSII complexes. We conclude
      that FtsH2 plays a major role in the degradation of both precursor and mature
      forms of D1 following donor-side photoinhibition. However, this conclusion
      concerned only D1 assembled into larger complexes containing at least D2 and
      CP47. In the DeltapsbEFLJ deletion mutant blocked at an early stage in PSII
      assembly, unassembled D1 protein was efficiently degraded in the absence of FtsH2
      pointing to the involvement of other protease(s). Significantly, the DeltaPsbO
      mutant displayed unusually low levels of cellular chlorophyll at extremely low
      light intensities. The possibilities that PSII repair may limit the availability
      of chlorophyll for the biogenesis of other chlorophyll-binding proteins and that
      PsbO might have a regulatory role in PSII repair are discussed.

PMID- 20153292
TI  - Specific motifs of the V-ATPase a2-subunit isoform interact with catalytic and
      regulatory domains of ARNO.
AB  - We have previously shown that the V-ATPase a2-subunit isoform interacts
      specifically, and in an intra-endosomal acidification-dependent manner, with the
      Arf-GEF ARNO. In the present study, we examined the molecular mechanism of this
      interaction using synthetic peptides and purified recombinant proteins in protein
      association assays. In these experiments, we revealed the involvement of multiple
      sites on the N-terminus of the V-ATPase a2-subunit (a2N) in the association with
      ARNO. While six a2N-derived peptides interact with wild-type ARNO, only two of
      them (named a2N-01 and a2N-03) bind to its catalytic Sec7-domain. However, of
      these, only the a2N-01 peptide (MGSLFRSESMCLAQLFL) showed specificity towards the
      Sec7-domain compared to other domains of the ARNO protein. Surface plasmon
      resonance kinetic analysis revealed a very strong binding affinity between this
      a2N-01 peptide and the Sec7-domain of ARNO, with dissociation constant
      KD=3.44x10(-7) M, similar to the KD=3.13x10(-7) M binding affinity between wild
      type a2N and the full-length ARNO protein. In further pull-down experiments, we
      also revealed the involvement of multiple sites on ARNO itself in the association
      with a2N. However, while its catalytic Sec7-domain has the strongest interaction,
      the PH-, and PB-domains show much weaker binding to a2N. Interestingly, an
      interaction of the a2N to a peptide corresponding to ARNO's PB-domain was
      abolished by phosphorylation of ARNO residue Ser392. The 3D-structures of the non
      phosphorylated and phosphorylated peptides were resolved by NMR spectroscopy, and
      we have identified rearrangements resulting from Ser392 phosphorylation. Homology
      modeling suggests that these alterations may modulate the access of the a2N to
      its interaction pocket on ARNO that is formed by the Sec7 and PB-domains.
      Overall, our data indicate that the interaction between the a2-subunit of V
      ATPase and ARNO is a complex process involving various binding sites on both
      proteins. Importantly, the binding affinity between the a2-subunit and ARNO is in
      the same range as those previously reported for the intramolecular association of
      subunits within V-ATPase complex itself, indicating an important cell biological
      role for the interaction between the V-ATPase and small GTPase regulatory
      proteins.

PMID- 20153290
TI  - Role of calcineurin, hnRNPA2 and Akt in mitochondrial respiratory stress-mediated
      transcription activation of nuclear gene targets.
AB  - Pathophysiological conditions causing mitochondrial dysfunction and altered
      transmembrane potential (psim) initiate a mitochondrial respiratory stress
      response, also known as mitochondrial retrograde response, in a variety of
      mammalian cells. An increase in the cytosolic Ca2+ [Ca2+]c as part of this
      signaling cascade activates Ca2+ responsive phosphatase, calcineurin (Cn).
      Activation of IGF1R accompanied by increased glycolysis, invasiveness, and
      resistance to apoptosis is a phenotypic hallmark of C2C12 skeletal muscle cells
      subjected to this stress. The signaling is associated with activation and
      increased nuclear translocation of a number of transcription factors including a
      novel NFkappaB (cRel:p50) pathway, NFAT, CREB and C/EBPdelta. This culminates in
      the upregulation of a number of nuclear genes including Cathepsin L, RyR1, Glut4
      and Akt1. We observed that stress regulated transcription activation of nuclear
      genes involves a cooperative interplay between NFkappaB (cRel:p50), C/EBPdelta,
      CREB, and NFAT. Our results show that the functional synergy of these factors
      requires the stress-activated heterogeneous nuclear ribonucleoprotein, hnRNPA2 as
      a transcriptional coactivator. We report here that mitochondrial stress leads to
      induced expression and activation of serine threonine kinase Akt1. Interestingly,
      we observe that Akt1 phosphorylates hnRNPA2 under mitochondrial stress
      conditions, which is a crucial step for the recruitment of this coactivator to
      the stress target promoters and culmination in mitochondrial stress-mediated
      transcription activation of target genes. We propose that mitochondrial stress
      plays an important role in tumor progression and emergence of invasive
      phenotypes.

PMID- 20153293
TI  - Interaction of the N-terminal segment of HCV protein NS5A with model membranes.
AB  - We have identified a membrane-active region in the HCV NS5A protein by performing
      an exhaustive study of membrane rupture induced by a NS5A-derived peptide library
      on model membranes having different phospholipid compositions. We report the
      identification in NS5A of a highly membranotropic region located at the suggested
      membrane association domain of the protein. We report the binding and interaction
      with model membranes of two peptides patterned after this segment, peptides 1A
      and 1B, derived from the strains 1a_H77 and 1b_HC-4J respectively. We show that
      they insert into phospholipid membranes, interact with them, and are located in a
      shallow position in the membrane. The NS5A region where this segment resides
      might have an essential role in the membrane replication and/or assembly of the
      viral particle through the modulation of the replication complex, and
      consequently, directly implicated in the HCV life cycle.

PMID- 20153294
TI  - Unravelling the molecular basis of the selectivity of the HIV-1 fusion inhibitor
      sifuvirtide towards phosphatidylcholine-rich rigid membranes.
AB  - Sifuvirtide, a 36 amino acid negatively charged peptide, is a novel HIV-1 fusion
      inhibitor with improved antiretroviral activity. In this work we evaluated the
      physical chemistry foundation of the interaction of sifuvirtide with biomembrane
      model systems. Since this peptide has aromatic residues, fluorescence
      spectroscopy techniques were mostly used. The interaction was assessed by
      partition and quenching experiments. Results showed no significant interaction
      with large unilamellar vesicles composed by sphingomyelin and ceramide. In
      contrast, sifuvirtide presented selectivity towards vesicles composed by
      phosphatidylcholines (PC) in the gel phase, in opposition to fluid phase PC
      vesicles. The interaction of this peptide with gel phase PC membranes
      (K(p)=1.2x10(2)) is dependent on the ionic strength, which indicates the
      mediation of electrostatic interactions at an interfacial level. The effects of
      sifuvirtide on the lipid membranes' structural properties were further evaluated
      using dipole-potential membrane probes, zeta-potential, dynamic light scattering
      and atomic force microscopy measurements. The results show that sifuvirtide does
      not cause a noticeable effect on lipid bilayer structure, except for membranes
      composed by cationic phospholipids. Altogether, we can conclude that sifuvirtide
      presents a specific affinity towards rigid PC membranes, and the interaction is
      mediated by electrostatic factors, not affecting the membrane architecture.

PMID- 20153295
TI  - Yap is a novel regulator of C2C12 myogenesis.
AB  - The expression, regulation and function of mammalian Hippo pathway members in
      skeletal muscle is largely unknown. The aim of this study was thus to test the
      hypothesis that core members of the mammalian Hippo pathway are expressed in
      skeletal muscle and that the transcriptional co-factor Yap, a core member of the
      Hippo pathway, regulates C2C12 myogenesis. We found that the major components of
      the mammalian Hippo pathway including Yap are all expressed in skeletal muscles,
      C2C12 myoblasts and myotubes. In C2C12 myoblasts, Yap Ser127 phosphorylation is
      low and Yap localises to nuclei. Upon differentiation, Yap Ser127 phosphorylation
      increases approximately 20-fold and Yap translocates from the nucleus to the
      cytosol. To test whether the observed increase of Yap Ser127 phosphorylation is
      required for differentiation we overexpressed hYAP1 S127A, a mutant that can not
      be phosphorylated at Ser127, in C2C12 myoblasts. We found that overexpression of
      hYAP S127A prevented myotube formation, whereas the overexpression of wildtype
      hYAP1 or empty vector had no effect. In addition, more hYAP1 S127A overexpressing
      cells progressed through the S phase of the cell cycle and the expression of MRFs
      (myogenin, Myf5), Mef2c and cell cycle regulators (p21, cyclin D1) was
      significantly changed when compared to wildtype hYAP1 and empty vector
      overexpressing cells. This data suggests that the phosphorylation of Yap at
      Ser127 leads to a changed expression of MRFs and cell cycle regulators and is
      required for C2C12 myoblasts to differentiate into myotubes.

PMID- 20153296
TI  - Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression
      by a HIF-1 independent mechanism.
AB  - Flavonoids are a group of polyphenolic dietary compounds that have been proposed
      to possess chemopreventive properties against lung cancer. In this work we
      analyzed the effect of a group of 20 structurally related flavonoids, including
      flavones, flavonols and isoflavones, on the production of vascular endothelial
      growth factor (VEGF) induced by hypoxia in NCI-H157 cells. VEGF is the main
      regulator of physiological and pathological angiogenesis and is highly stimulated
      by hypoxia-inducible factor 1 (HIF-1). We found that apigenin, luteolin, fisetin
      and quercetin inhibited hypoxia-induced VEGF expression in the low micromolar
      range. Structure-activity relationships demonstrated that flavone derivatives
      were the most active compounds and that hydroxylation of the A ring at the
      positions 5 and 7 and of the B ring at the 4' position were important for this
      activity. Interestingly, only a group of VEGF inhibitors, including apigenin,
      flavone and 4',7-dihydroxiflavone, reduced the expression of HIF-1alpha under
      these conditions, whereas others, such as fisetin, luteolin, galangin or
      quercetin, induced HIF-1alpha expression while reducing those of VEGF. When cells
      were exposed to hypoxia in the presence of these flavonoids, HIF-1alpha
      translocated to the nucleus and interacted with p300/CBP, but this complex was
      transcriptionally inactive. Taken together these findings indicate that
      flavonoids impair VEGF transcription by an alternative mechanism that did not
      depend on nuclear HIF levels. We also found that flavonoids suppressed hypoxia
      induced STAT3 tyrosine phosphorylation and that this activity correlated with
      their potency as VEGF inhibitors, suggesting that inhibition of STAT3 function
      may play a role in this process.

PMID- 20153297
TI  - Audiovisual integration of emotional signals from music improvisation does not
      depend on temporal correspondence.
AB  - In the present study we applied a paradigm often used in face-voice affect
      perception to solo music improvisation to examine how the emotional valence of
      sound and gesture are integrated when perceiving an emotion. Three brief excerpts
      expressing emotion produced by a drummer and three by a saxophonist were
      selected. From these bimodal congruent displays the audio-only, visual-only, and
      audiovisually incongruent conditions (obtained by combining the two signals both
      within and between instruments) were derived. In Experiment 1 twenty musical
      novices judged the perceived emotion and rated the strength of each emotion. The
      results indicate that sound dominated the visual signal in the perception of
      affective expression, though this was more evident for the saxophone. In
      Experiment 2 a further sixteen musical novices were asked to either pay attention
      to the musicians' movements or to the sound when judging the perceived emotions.
      The results showed no effect of visual information when judging the sound. On the
      contrary, when judging the emotional content of the visual information, a
      worsening in performance was obtained for the incongruent condition that combined
      different emotional auditory and visual information for the same instrument. The
      effect of emotionally discordant information thus became evident only when the
      auditory and visual signals belonged to the same categorical event despite their
      temporal mismatch. This suggests that the integration of emotional information
      may be reinforced by its semantic attributes but might be independent from
      temporal features.

PMID- 20153298
TI  - Stimulus and response conflict in the color-word Stroop task: a combined electro
      myography and event-related potential study.
AB  - We aimed to separate stimulus and response conflict in a manual color-word Stroop
      task by combining electro-myography (EMG) and event-related brain potentials
      (ERPs). EMG served as a measure of response conflict by detecting incorrect
      response hand activation in correctly responded trials. Response conflict was
      enhanced in both the incongruent and congruent conditions relative to neutral
      conditions. This suggests that the Stroop conflict (incongruent vs. congruent
      condition) could be explained by stimulus conflict in our study and that response
      conflict was not restricted to the incongruent condition of the Stroop task.
      Incorrect response activity was detected in a neutral condition using words but
      not in a neutral condition with non-words. This suggests that the mere presence
      of task-irrelevant stimuli semantically related to task-relevant stimuli can
      prime incorrect response activity. The above factors are important to consider in
      studies which do not have any explicit measure of response conflict. We have
      detected a robust marker of Stroop conflict, the N450 ERP effect, which has been
      related to ACC activity. The N450 was probably affected by stimulus conflict in
      our study and it may be a marker of general conflict processing.

PMID- 20153299
TI  - An electrophysiological study of boundary conditions for control of recollection
      in the exclusion task.
AB  - Event-related potentials (ERPs) were collected in a memory retrieval task that
      was designed to assess the resolution with which people exerted control over
      memory retrieval. Participants were first required to indicate whether the
      objects denoted by concrete nouns (i) had pleasant or unpleasant connotations,
      (ii) were typically smaller or larger than a shoebox, or (iii) were easy or
      difficult to draw. They then completed a retrieval task where old (studied) and
      new words were presented. Participants pressed one key for words encountered in
      the drawing task, and a second key for all other test words (new words as well as
      those encountered in the pleasantness and size judgment tasks). The left-parietal
      ERP old/new effect--an electrophysiological index of recollection--was reliable
      for words from the drawing task only. This finding is consistent with the view
      that participants were successful at prioritising recollection of some kinds of
      information over others. The data also provide an insight into the resolution
      with which this prioritisation can be implemented, because there was little
      evidence of a left-parietal ERP old/new effect for words to which a size judgment
      was made, despite the fact that visual imagery is likely to have been employed
      for drawing as well as for size judgments.

PMID- 20153300
TI  - Noradrenergic lesion of the locus coeruleus increases the firing activity of the
      medial prefrontal cortex pyramidal neurons and the role of alpha2-adrenoceptors
      in normal and medial forebrain bundle lesioned rats.
AB  - Degeneration of noradrenergic neurons in the locus coeruleus (LC) and dysfunction
      of the prefrontal cortex were regarded as playing a specific role in the
      occurrence of non-motor symptoms in Parkinson's disease. The present study
      examined the spontaneous firing rate and firing pattern of medial prefrontal
      cortex (mPFC) pyramidal neurons, and effects of alpha(2)-adrenoceptor agonist UK
      14,304 and antagonist yohimbine on the neuronal activity in rats with 6
      hydroxydopamine lesions of the LC, medial forebrain bundle (MFB) and with
      combined MFB and LC lesions. The firing rate of mPFC pyramidal neurons in rats
      with lesions of the LC and with combine LC and MFB lesions is significantly
      higher than that of normal and MFB-lesioned rats and the firing pattern of these
      neurons in rats with lesions of the LC and with combine LC and MFB lesions also
      changed significantly towards more regular compared with normal and MFB-lesioned
      rats. The local administration of UK-14,304 in the mPFC inhibited the firing
      activity of the pyramidal neurons in normal rats and rats with lesions of the LC,
      MFB and with combined LC and MFB lesions, while yohimbine increased the firing
      activity of the pyramidal neurons. These results indicate that the lesions of the
      LC lead to hyperactivity of mPFC pyramidal neurons in normal and MFB-lesioned
      rats, and the postsynaptic alpha(2)-adrenoceptors may partially mediate the
      inhibitory effects of LC-noradrenergic system on the firing activity of pyramidal
      neurons in the mPFC, suggesting that LC-noradrenergic system plays an important
      role in the functional disorders of mPFC in Parkinson's disease.

PMID- 20153301
TI  - Sex differences in face gender recognition: an event-related potential study.
AB  - Multiple level neurocognitive processes are involved in face processing in
      humans. The present study examined whether the early face processing such as
      structural encoding is modulated by task demands that manipulate attention to
      perceptual or social features of faces and such an effect, if any, is different
      between men and women. Event-related brain potentials were recorded from male and
      female adults while they identified a low-level perceptual feature of faces
      (i.e., face orientation) and a high-level social feature of faces (i.e., gender).
      We found that task demands that required the processing of face orientations or
      face gender resulted in modulations of both the early occipital/temporal
      negativity (N170) and the late central/parietal positivity (P3). The N170
      amplitude was smaller in the gender relative to the orientation identification
      task whereas the P3 amplitude was larger in the gender identification task
      relative to the orientation identification task. In addition, these effects were
      much stronger in women than in men. Our findings suggest that attention to social
      information in faces such as gender modulates both the early encoding of facial
      structures and late evaluative process of faces to a greater degree in women than
      in men.

PMID- 20153302
TI  - Muscarinic modulation of TASK-like background potassium channel in rat carotid
      body chemoreceptor cells.
AB  - The carotid body is the main peripheral arterial chemoreceptor and it is
      essential to initiate the cardiovascular and respiratory compensatory reflex
      responses to a decrease in the arterial oxygen. The carotid body chemoreceptor
      (type-I) cells respond to hypoxia with membrane depolarization, voltage-gated
      Ca(2+) entry and secretion of transmitters. A key step in this response is the
      inhibition of a TASK-like background K(+) current. It has been reported that TASK
      K(+) channels can be modulated by G-protein coupled receptors, such as the
      muscarinic acetylcholine receptor (mAChRs). Since there is a proposed role for
      ACh as an autocrine/paracrine modulator of the carotid body function, we have
      investigated the possible regulation of the background K(+) current by mAChRs. In
      identified type-I cells, methacholine (100microM) or muscarine (50microM)
      increased intracellular Ca(2+) levels. In cell-attached patch recordings, TASK
      K(+) background channel activity was reduced by approximately 50% during mAChR
      activation and by the diacylglycerol analogue oleoylacetylglycerol (OAG,
      20microM). The co-application of both metacholine and OAG do not further inhibit
      K(+) channel activity. In addition, two chemically different inhibitors of
      protein kinase C activity, calphostin C (100nM) and chelerythrine (50microM) are
      both able to suppress the muscarinic inhibition of the TASK-like K(+) channel and
      to increase channel activity in the absence of mAChR agonists. Our results
      suggest a muscarinic regulation of the TASK-like K(+) current in rat carotid body
      type-I cells through a PLC/PKC-dependent pathway. Additionally, our findings are
      consistent with an autocrine/paracrine role for cholinergic autoreceptors present
      within the carotid body.

PMID- 20153303
TI  - Proposed mode of action of benzene-induced leukemia: Interpreting available data
      and identifying critical data gaps for risk assessment.
AB  - Mode of action is defined as a series of key biological events leading to an
      observed toxicological effect (for example, metabolism to a toxic entity, cell
      death, regenerative repair and tumors). It contrasts with mechanism of action,
      which generally involves a detailed understanding of the molecular basis for an
      effect. A framework to consider the weight of evidence for hypothesized modes of
      action in animals and their relevance to humans, has been widely adopted and used
      by government agencies and international organizations. The framework, developed
      and refined through its application in case studies for principally non-DNA
      reactive carcinogens, has more recently been extended to DNA-reactive
      carcinogens, non-cancer endpoints and different life stages. In addition to
      increasing transparency, use of the framework promotes consistency in decision
      making concerning adequacy of weight of evidence, facilitates peer input and
      review and identifies critical research needs. The framework provides an
      effective tool to facilitate discussion between the research and risk assessment
      communities on critical data gaps, which if filled, would permit more refined
      estimates of risk. As a basis for additionally coordinating and focusing research
      on critical data gaps in a risk assessment context, five key events in the mode
      of action for benzene-induced leukemia are proposed: (1) benzene metabolism via
      Cytochrome P450, (2) the interaction of benzene metabolites with target cells in
      the bone marrow, (3) formation of initiated, mutated target cells, (4) selective
      proliferation of the mutated cells and (5) production of leukemia. These key
      events are considered in a framework analysis of human relevance as a basis to
      consider appropriate next steps in developing research strategies.

PMID- 20153304
TI  - Contributions of selective knockout studies to understanding cholinesterase
      disposition and function.
AB  - The complete knockout of the acetylcholinesterase gene (AChE) in the mouse
      yielded a surprising phenotype that could not have been predicted from deletion
      of the cholinesterase genes in Drosophila, that of a living, but functionally
      compromised animal. The phenotype of this animal showed a sufficient compromise
      in motor function that precluded precise characterization of central and
      peripheral nervous functional deficits. Since AChE in mammals is encoded by a
      single gene with alternative splicing, additional understanding of gene
      expression might be garnered from selected deletions of the alternatively spliced
      exons. To this end, transgenic strains were generated that deleted exon 5, exon
      6, and the combination of exons 5 and 6. Deletion of exon 6 reduces brain AChE by
      93% and muscle AChE by 72%. Deletion of exon 5 eliminates AChE from red cells and
      the platelet surface. These strains, as well as knockout strains that selectively
      eliminate the AChE anchoring protein subunits PRiMA or ColQ (which bind to
      sequences specified by exon 6) enabled us to examine the role of the
      alternatively spliced exons responsible for the tissue disposition and function
      of the enzyme. In addition, a knockout mouse was made with a deletion in an
      upstream intron that had been identified in differentiating cultures of muscle
      cells to control AChE expression. We found that deletion of the intronic
      regulatory region in the mouse essentially eliminated AChE in muscle and
      surprisingly from the surface of platelets. The studies generated by these
      knockout mouse strains have yielded valuable insights into the function and
      localization of AChE in mammalian systems that cannot be approached in cell
      culture or in vitro.

PMID- 20153305
TI  - Cholinesterases regulation in the absence of ColQ.
AB  - Normal physiological activity of the neuromuscular junction (NMJ) requires that
      key molecules are clustered at the synapse. One of these molecules is
      acetylcholinesterase (AChE) that regulates acetylcholine levels. This enzyme
      exists under different isoforms but the predominant form at the NMJ is a collagen
      tailed enzyme. The collagen associated to AChE (ColQ) fulfills two functions. It
      anchors and accumulates AChE in the extracellular matrix. Mutations in ColQ lead
      to faint or no activity of AChE in the synaptic cleft. As a consequence, normal
      NMJ functioning is impaired and myasthenic syndromes are observed in patients
      bearing these mutations. Here, we investigated the effects of ColQ deficiency on
      cholinesterases mRNA levels and cluster formation. We show that overexpression of
      AChE but not ColQ in muscle cells is sufficient to drive the formation of AChE
      clusters. The absence of ColQ in muscle cells in vitro and in vivo leads to an
      increase in AChE(R) and AChE(T) mRNAs, corresponding to two isoforms of AChE.
      However, AChE activity is decreased in the medium of ColQ-deficient cells
      suggesting that AChE secretion is impaired. Butyrylcholinesterase (BChE) mRNAs
      are also upregulated in vivo. Since AChE and BChE can associate with PRiMA, a
      membrane anchor, we explored the pattern of expression of PRiMA in vitro and in
      vivo. The level of PRiMA transcripts is downregulated in the absence of ColQ.
      Therefore, AChE, BChE and PRiMA mRNA level modifications found in the absence of
      ColQ cannot compensate for the physiological defects observed at the ColQ
      deficient NMJs.

PMID- 20153306
TI  - Investigating the membrane orientation and transversal distribution of 17beta
      estradiol in lipid membranes by solid-state NMR.
AB  - 17beta-Estradiol (E(2)) is a potent estrogen, which modulates many important
      cellular functions by binding to specific estrogen receptors located in the cell
      nucleus and also on the plasma membrane. We have studied the membrane interaction
      of E(2) using a combination of solid-state NMR methods. (2)H NMR results indicate
      that E(2) does not cause a condensation effect of the surrounding phospholipids,
      which is contrary to the effects of cholesterol, and only very modest E(2)
      induced alterations of the membrane structure were detected. (1)H magic-angle
      spinning NMR showed well resolved signals from E(2) as well as of POPC in the
      membrane-lipid layer. Two-dimensional NOESY spectra revealed intense cross-peaks
      between E(2) and the membrane lipids indicating that E(2) is stably inserted into
      the membrane. The determination of intermolecular cross-relaxation rates revealed
      that E(2) is broadly distributed in the membrane with a maximum of the E(2)
      distribution function in the upper chain region of the membrane. We conclude that
      E(2) is highly dynamic in lipid membranes and may undergo rotations as it
      exhibits two polar hydroxyl groups on either side of the molecule.

PMID- 20153307
TI  - High-throughput tissue homogenization method and tissue-based quality control
      materials for a clinical assay of the intestinal disaccharidases.
AB  - BACKGROUND: The definitive biochemical test for the diagnosis of disaccharidase
      deficiencies is the determination of enzyme activities in small bowel mucosa.
      Traditional methods of tissue homogenization are limited by low throughput. Lack
      of tissue-based quality control materials is a limitation for clinical
      laboratories that perform tests of the intestinal disaccharidases. The objectives
      of this study were to develop a method for determining disaccharidase activities
      using a high-throughput homogenization method and to create matrix-appropriate
      quality control materials. METHODS: Intestinal mucosa was homogenized using three
      different methods. Activities of lactase, maltase, palatinase, and sucrase were
      determined by measuring glucose liberated from a hydrolysis reaction with
      disaccharide substrates and normalized to total protein concentration. Tissue
      based quality control materials were developed from pig intestine and pooled
      clinical specimens. RESULTS: A high-throughput homogenization method processed 24
      specimens in 2 min compared to 1 specimen per 2 min for traditional methods.
      There were no significant differences (p>0.90) in enzyme activities as a function
      of the homogenization method used. 92 determinations of enzyme activities from 23
      clinical specimens showed acceptable agreement (y=1.13x-6.6) and were highly
      correlated (r=0.95) as compared to results obtained by an external laboratory.
      Enzyme activities were variably inactivated by temperatures > or = 60 degrees C.
      Pig intestinal mucosa produced non-deficient enzyme activities while deficient
      activities were produced by combining equal volumes of unheated and heat
      inactivated homogenates pooled from clinical specimens. CONCLUSIONS: A high
      throughput method of tissue homogenization was more efficient than traditional
      methods and did not affect enzyme activities. Matrix-appropriate quality control
      materials can be created from pig intestine and pooled human homogenates.

PMID- 20153308
TI  - Prognostic value of established and novel biomarkers in patients with shortness
      of breath attending an emergency department.
AB  - OBJECTIVES: Acute dyspnea is a common cause for emergency department visits. The
      aim of this study was to evaluate the prognostic value of established and novel
      biomarkers in patients with acute dyspnea. DESIGN AND METHODS: We measured 10
      biomarkers [B-type natriuretic peptide (BNP), midregional pro-A-type natriuretic
      peptide (MR-proANP), midregional-proadrenomedullin (MR-proADM), copeptin, C
      terminal endothelin-1 precursor fragment (CT-proET-1), soluble ST2 (sST2),
      chromogranin A (CgA), adiponectin, proguanylin, and prouroguanylin] in 251
      consecutive patients with acute dyspnea presenting to the emergency department of
      a tertiary care hospital. Outcome measure was all-cause mortality at 1 year.
      RESULTS: At baseline decedents (n=62) had significantly higher median plasma
      concentrations of all 10 biomarkers than survivors (n=189). Applying univariate
      Cox proportional-hazard regression analyses, all biomarkers were significant
      outcome predictors displaying risk ratios (RR) from 1.4 to 2.4 (per 1 SD increase
      in log transformed values). In multivariate Cox proportional-hazard regression
      analysis, however, only MR-proANP (RR 1.6; 95% CI, 1.1-2.2; p=0.008), sST2 (RR
      1.7; 95% CI, 1.3-2.3; p<0.001), and CgA (RR 1.5; 95% CI, 1.2-1.9, p<0.001) were
      independently associated with 1-year mortality. We provide a possible explanation
      for the complementary prognostic value of those three biomarkers in our cohort,
      where coincidence of heart failure and inflammatory pulmonary disease was common
      and also related to worse outcome. CONCLUSIONS: Our evaluation of biomarkers in
      patients with acute dyspnea suggests that MR-proANP, sST2, and CgA are strong,
      independent and complementary outcome predictors. MR-proANP is considered a
      specific marker of cardiac stretch, sST2 might reflect both inflammation and
      cardiac stretch, and CgA obviously indicates neuroendocrine activation in various
      diseases.

PMID- 20153309
TI  - Multi-center determination of galectin-3 assay performance characteristics:
      Anatomy of a novel assay for use in heart failure.
AB  - BACKGROUND: Galectin-3 is a carbohydrate binding protein that plays many
      important regulatory roles in inflammation, immunity and cancer. Recent studies
      indicate that galectin-3 is a mediator of heart failure development and
      progression. Development of an improved assay for galectin-3 measurement was
      necessary for appropriate clinical assessment. Key analytical performance
      characteristics, the reference distribution and association of galectin-3 levels
      with clinical outcome in heart failure patients are defined. METHODS: A two-site
      ELISA test was examined for measurement matrix, imprecision, limits of blank,
      detection, and quantitation, as well as linearity, high-dose hook effect, storage
      stability, cross-reactivity with nine similar compounds, interference with 22
      common medications and icterus, lipemia and hemolysis, all in accordance with
      CLSI guidance. Also the effects of human anti-mouse antibodies and rheumatoid
      factor on recovery of galectin-3 were investigated. The reference interval was
      determined for 1092 ostensibly healthy individuals. The association of galectin-3
      concentrations with an outcome of mortality was examined in a preliminary
      analysis of 129 acute decompensated heart failure patients. RESULTS: Galectin-3
      results were equivalent when measured in serum or EDTA plasma. Imprecision
      studies demonstrated that the total CV was <10% at a low concentration of 6
      ng/mL, 7% near the mid-level concentration of 21 ng/mL, and 15% at the high level
      of 70 ng/mL. The limit of blank was 0.86 ng/mL, the limit of detection was 1.13
      ng/mL, and the limit of quantitation was 0.96 ng/mL. The linear measurement range
      was 0.96-130 ng/mL and there was no high-dose hook at levels up to 500 ng/mL. No
      cross-reactivity with nine compounds structurally related to galectin-3 and no
      interference from 22 common medications, icterus or lipemia was found. Hemolysis
      and presence of human anti-mouse antibodies or rheumatoid factor were found to be
      potential sources of interference. Samples can be stored for up to 15 days at
      either 22-28 degrees C or 2-8 degrees C before analysis; measurements are stable
      after storage at -20 degrees C or -70 degrees C for at least 6 months and through
      six freeze-thaw cycles. The 90th, 95th and 97.5th percentile of the normal
      reference interval was 17.6, 20.3 and 22.1 ng/mL, respectively. Galectin-3 in the
      acute decompensated heart failure patients ranged from 4.0 to 75 ng/mL; using a
      cutpoint of 22.1 ng/mL in an unadjusted analysis, galectin-3 values were
      associated with an outcome of death (p=0.035). Galectin-3 is associated with
      severity of heart failure as indicated by NYHA Class (p-value for trend, 0.017).
      CONCLUSION: This ELISA for galectin-3 measurement demonstrated acceptable
      analytical characteristics and was associated with mortality in a preliminary
      unadjusted analysis.

PMID- 20153310
TI  - HPLC-FLU detection of cortisol distribution in human hair.
AB  - OBJECTIVE: Recently cortisol level in hair is supposed to be a good biomarker of
      chronic stress. We had developed a new method based on HPLC-FLU for
      identification of cortisol in human hair and measured cortisol distribution of
      each 1-cm segment along hair shaft. DESIGN AND METHODS: Hair sample was
      pulverized and incubated in 0.1 M HCl and extracted with ethyl acetate. The
      extraction was derived with sulfuric acid. The derivative was extracted with SPE
      C18 column. RESULTS: The detection limit was 1 pg/mg, the intraday and interday
      precisions were 7.3% and 8.5%, and average recovery was 102.5+/-13.0%. Cortisol
      concentrations of 32 humans' hair ranged from 3.28 to 24.83 pg/mg. There was a
      distinct decline in the cortisol of 1-cm segment along hair shaft. CONCLUSIONS:
      This method showed that the precision was matched with mass spectroscopy. The
      cortisol in 1-cm hair segment sensitively reflects a retrospective calendar over
      1 month.

PMID- 20153311
TI  - Replication origins are already licensed in G1 arrested unfertilized sea urchin
      eggs.
AB  - Fertilization relieves the oocyte from a cell cycle arrest, inducing progression
      towards mitotic cycles. While the signalling pathways involved in oocyte to
      embryo transition have been widely investigated, how they specifically trigger
      DNA replication is still unclear. We used sea urchin eggs whose oocytes are
      arrested in G1 to investigate in vivo the molecular mechanisms regulating
      initiation of replication after fertilization. Unexpectedly, we found that CDC6,
      Cdt1 and MCM3, components of the pre-replication complexes (pre-RC) which license
      origins for replication, were already loaded on female chromatin before
      fertilization. This is the first demonstration of a cell cycle arrest in metazoan
      in which chromatin is already licensed for replication. In contrast pre-RC
      assemble on chromatin post-fertilization as in other organisms. These differences
      in the timing of pre-RC assembly are accompanied by differences in Cdk2
      requirement for DNA replication initiation between female and male chromatin post
      fertilization. Finally, we demonstrated that a concomitant inhibition of MAP
      kinase and ATM/ATR pathways releases the block to DNA synthesis. Our findings
      provide new insight into the mechanisms contributing to the release of G1 arrest
      and the control of S-phase entry at fertilization.

PMID- 20153312
TI  - Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute
      lung injury in mice.
AB  - Lipopolysaccharides from gram-negative bacteria are amongst the most common
      causative agents of acute lung injury, which is characterized by an inflammatory
      response, with cellular infiltration and the release of mediators/cytokines.
      There is evidence that bradykinin plays a role in lung inflammation in asthma but
      in other types of lung inflammation its role is less clear. In the present study
      we evaluated the role of the bradykinin B1 receptor in acute lung injury caused
      by lipopolysaccharide inhalation and the mechanisms behind bradykinin actions
      participating in the inflammatory response. We found that in C57Bl/6 mice, the
      bradykinin B1 receptor expression was up-regulated 24h after lipopolysaccharide
      inhalation. At this time, the number of cells and protein concentration were
      significantly increased in the bronchoalveolar lavage fluid and the mice
      developed airway hyperreactivity to methacholine. In addition, there was an
      increased expression of tumor necrosis factor-alpha, interleukin-1 beta and
      interferon-gamma and chemokines (monocytes chemotactic protein-1 and KC) in the
      bronchoalveolar lavage fluid and in the lung tissue. We then treated the mice
      with a bradykinin B1 receptor antagonist, R-954 (Ac-Orn-[Oic2, alpha-MePhe5, D
      betaNal7, Ile8]desArg9-bradykinin), 30 min after lipopolysaccharide
      administration. We observed that this treatment prevented the airway
      hyperreactivity as well as the increased cellular infiltration and protein
      content in the bronchoalveolar lavage fluid. Moreover, R-954 inhibited the
      expression of cytokines/chemokines. These results implicate bradykinin, acting
      through B1 receptor, in the development of acute lung injury caused by
      lipopolysaccharide inhalation.

PMID- 20153313
TI  - Expression of NR3B but not NR2D subunit of NMDA receptor in human blood
      lymphocytes can serve as a suitable peripheral marker for opioid addiction
      studies.
AB  - Glutamate is critically involved in opioid addiction. It has been suggested that
      neurotransmitter receptors expression in peripheral blood lymphocytes may reflect
      brain status. In the present study, using Real-time PCR, the mRNA expression of
      NR2D and NR3B subunits of NMDA glutamate receptor has been investigated in
      peripheral blood lymphocytes of four groups each comprising of 25 male
      individuals: opioid addicts, methadone maintained patients, long-term abstinent
      former opioid addicts, and non-addicted control subjects. We found that NR2D
      subunit mRNA expression was not changed in all three test groups in comparison to
      control subjects. However, the NR3B mRNA expression was significantly up
      regulated by the factors 9.11 (P<0.001), 10.07 (P<0.001) and 4.08 (P<0.05) in
      abstinent, addicted and methadone maintained subjects, respectively relative to
      control group. As a conclusion, our data indicate that the transcriptional level
      of the NR2D subunit of NMDA receptor is not regulated by chronic opioid
      addiction. However, it seems that the over-expression of NR3B subunit of NMDA
      receptor is a long lasting result of opioid abuse. In addition, considerable
      decrease in the up-regulated state of the NR3B subunit by methadone may represent
      another benefit of methadone therapy for opioid addicts and may serve as a
      suitable marker to evaluate the successfulness of therapy.

PMID- 20153314
TI  - Effects of cannabinoid receptor antagonists on maintenance and reinstatement of
      methamphetamine self-administration in rhesus monkeys.
AB  - Cannabinoid receptor antagonists have shown some promise as treatments capable of
      reducing abuse and relapse to a number of abused drugs. In rodents, such effects
      have been observed with methamphetamine self-administration. However, the effects
      of cannabinoid receptor antagonists on methamphetamine self-administration and
      relapse have not been studied in primates. In the present study, rhesus monkeys
      were trained to respond on a three-component operant schedule. During the first 5
      min component, fixed-ratio responses were reinforced by food, during the second
      90- or 180-min component fixed-ratio responses were reinforced by i.v.
      methamphetamine. The third component was identical to the first. There was a 5
      min timeout between each component. The effects of the cannabinoid receptor
      antagonists AM 251 and rimonabant were tested at various doses against self
      administration of 3microg/kg/injection methamphetamine, and 1mg/kg AM 251 and
      0.3mg/kg rimonabant were tested against the methamphetamine dose-effect function.
      The 1mg/kg dose of AM 251 was also tested for its ability to alter reinstatement
      of extinguished self-administration responding. The cannabinoid receptor
      antagonist AM 251 was found to reduce methamphetamine self-administration at
      doses that did not affect food-reinforced responding. The cannabinoid receptor
      antagonist rimonabant had similar, but less robust effects. AM 251 also prevented
      reinstatement of extinguished methamphetamine seeking that was induced by re
      exposure to a combination of methamphetamine and methamphetamine-associated cues.
      These results indicate that cannabinoid receptor antagonists might have
      therapeutic effects for the treatment of methamphetamine dependence.

PMID- 20153315
TI  - Preconditioning protects against oxidative injury involving hypoxia-inducible
      factor-1 and vascular endothelial growth factor in cultured astrocytes.
AB  - Tolerance to brain injury involves hypoxia-inducible factor-1 (HIF-1) and its
      target genes as the key pathway mediating a cascade of events including cell
      survival, energetics, and angiogenesis. In this study, we established the
      treatment paradigms for an in vitro model of tolerance to oxidative injury in
      primary astrocytic cultures and further examined the roles for the HIF-1
      signalling cascade. Isolated murine astrocytes were preconditioned with sub-toxic
      concentrations of HIF-1 inducers and subsequently exposed to a H(2)O(2) insult,
      where changes in cell viability and protein expression were determined.
      Preconditioning with non-damaging concentrations of desferrioxamine (DFO) and
      ethyl-3,4-dihydroxybenzoate (EDHB) significantly improved cellular viability
      after H(2)O(2) injury treatment. Time course studies revealed that DFO and EDHB
      treatments alone induced sequential activation of HIF-1 signal transduction where
      nuclear HIF-1alpha protein accumulation was detected as early as 2h, followed by
      downstream upregulation of intracellular and released VEGF from 4h and 8h
      onwards, respectively. The protective effects of DFO and EDHB preconditioning
      against H(2)O(2) injury were abolished by co-treatment with cycloheximide, an
      inhibitor of protein synthesis. Importantly, when the anti-HIF-1 compound, 3-(5'
      hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) was used, the cytoprotection and
      VEGF accumulation produced by DFO and EDHB preconditioning were diminished. These
      results indicate the essential role of the HIF-1 pathway in our model of
      tolerance against oxidative injury in cultured astrocytes, and suggest roles for
      astrocytic HIF-1 expression and VEGF release which may influence the function of
      surrounding cells and vasculature during oxidative stress-related brain diseases.

PMID- 20153316
TI  - Binding of [(3)H]A-778317 to native transient receptor potential vanilloid-1
      (TRPV1) channels in rat dorsal root ganglia and spinal cord.
AB  - A-778317 (1-((R)-5-tert-butyl-indan-1-yl)-3-isoquinolin-5-yl-urea) is a potent
      antagonist of human and rat transient receptor potential vanilloid-1 (TRPV1)
      receptors. We have previously reported that [(3)H]A-778317 is an excellent
      radioligand to study the recombinant human TRPV1 receptor in a heterologous
      expression system. These studies were extended to determine the feasibility of
      using [(3)H]A-778317 to label native TRPV1 channels in rat tissues. Saturable
      high-affinity binding of [(3)H]A-778317 was detected in membrane preparations of
      rat dorsal root ganglia (DRG) and spinal cord that was inhibited by TRPV1
      receptor agonists and antagonists. [(3)H]A-778317 labeled a single class of high
      affinity binding sites in both rat DRG and spinal cord membranes (K(D)=10 and
      8.4nM, respectively). The number of binding sites was 10-fold higher in rat DRG
      membranes than spinal cord membranes (B(max)=3.3 and 0.35pmol/mg protein,
      respectively). The pharmacology of the high-affinity binding sites was similar in
      rat DRG and spinal cord, but differed from the recombinant rat TRPV1 (rTRPV1)
      receptor expressed in transiently transfected HEK293-F cells. In particular, a
      large disparity in potency (>300-fold) was observed for the TRPV1 receptor
      agonist resiniferatoxin between native and recombinant rTRPV1 receptors. Our data
      indicate that the binding of [(3)H]A-778317 to native rTRPV1 channels is
      pharmacologically distinct, and perhaps more complex, than its binding to the
      recombinant rTRPV1 receptor.

PMID- 20153317
TI  - Adenosine receptors as drug targets.
AB  - There are four adenosine receptors, A(1), A(2A), A(2B) and A(3), together forming
      a defined subgroup of G protein coupled receptors. They are well conserved and
      widely expressed. The endogenous agonist, adenosine, has a minimal concentration
      in body fluids (20-200 nM) that is sufficient to slightly activate the receptors
      where they are very highly expressed-as in the basal ganglia, on fat cells and in
      the kidney. Here adenosine can play a physiological role and here antagonists
      such as caffeine can have effects in healthy individuals. Adenosine levels rise
      in stress and distress (up to 30 microM in ischemia) and tend to minimize the
      risk for adverse outcomes by increasing energy supply and decreasing cellular
      work, by stimulating angiogenesis, mediating preconditioning and having multiple
      effects on immune competent cells. These pathophysiological roles of adenosine
      also offer some potential drug targets, but the fact that adenosine receptors are
      involved in so many processes does not simplify drug development.

PMID- 20153318
TI  - Caveolin-1 mutants P132L and Y14F are dominant negative regulators of invasion,
      migration and aggregation in H1299 lung cancer cells.
AB  - Caveolin-1 is an essential protein constituent of caveolae. Accumulating evidence
      indicates that caveolin-1 may act as a positive regulator of cancer progression.
      In this study, we investigated the function of caveolin-1 in human lung cancer
      cells. Caveolin-1 knockdown inhibited cell proliferation and reduced focal
      adhesion kinase (Fak) phosphorylation. Matrix invasion and cell migration as well
      as expression and activity of matrix metalloproteases were attenuated following
      caveolin-1 RNAi-mediated knockdown or overexpression of Y14F and P132L mutants,
      demonstrating dominant-negative activity of these mutants. Time-lapse
      fluorescence microscopy revealed that caveolin-1 and its mutants P132L and Y14F
      are localized to the trailing edge of migrating cells during both random and
      directed cell movement, implying an active role of caveolin-1 in the migration
      process. Suppression of caveolin-1 function greatly elevated the percentage of
      H1299 cells exhibiting focal adhesions. In addition, cell aggregation was
      increased by wild type caveolin-1 and attenuated by both P132L and Y14F mutants.
      Overexpression of wild type caveolin-1 increased caveolae density, however, P132L
      and Y14F mutants did not affect caveolae formation, suggesting that in this
      respect that the mutants do not act in a dominant negative manner, and that
      effects of caveolin-1 on caveolae and cell invasion, migration, focal adhesion
      and aggregation, are separable. Our data provide novel mechanistic insights into
      the role of caveolin-1 in cell motility, invasiveness and aggregation, therefore,
      expanding our understanding of the tumor-promoting activities of caveolin-1 in
      advanced-stage cancer.

PMID- 20153319
TI  - Role of matrix metalloproteinases in recurrent corneal melting.
AB  - The aim of this study was to compare the presence and activity of matrix
      metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9 and 13 in human melted and cadaverous
      corneas. Twelve melted corneal specimens from three patients with rheumatoid
      arthritis, one patient with ocular cicatricial pemphigoid and one patient with
      melting attributed to spastic entropion and ten control corneal buttons were
      used. The presence of MMPs was detected using indirect enzyme
      immunohistochemistry. The active forms of MMP-2 and -9 and MMP-3 and -7 were
      examined by gelatin and casein zymography, respectively. The concentrations of
      active MMP-1 and -3 were measured using activity assays. Increased immunostaining
      intensity for MMP-1 and -9 was seen in the corneal epithelium and the anterior
      stroma of all, and for MMP-2, -3, -7 and -8 of almost all, melted corneas
      compared to the negative or slightly positive staining of the controls. The
      posterior stroma showed the presence of MMP-1, -2, -3 and -9 in almost all and of
      MMP-7 and -8 in half of all melted specimens. A markedly higher level of active
      MMP-2 was detected in six and active MMP-9 in all of eleven pathologic specimens
      compared to control specimens, using gelatin zymography. The proenzymes of MMP-3
      and -7 and the MMP-7 intermediate cleavage product were detected only in melted
      corneas using casein zymography. Significantly increased MMP-1 and -3 activity
      was also found in the melted corneas using activity assays. The markedly
      increased immunostaining for MMP-1, -2, -3, -7, -8 and -9 as well as the elevated
      levels of the active forms of MMP-1, -2, -3 and -9 in melted corneal specimens
      from patients with various diagnoses suggest that although different stimuli may
      trigger the pathways that lead to the destruction of the extracellular matrix,
      these enzymes could play a subsequent role in this process.

PMID- 20153320
TI  - Long-term observation of auto-cell transplantation in non-human primate reveals
      safety and efficiency of bone marrow stromal cell-derived Schwann cells in
      peripheral nerve regeneration.
AB  - Based on their differentiation ability, bone marrow stromal cells (MSCs) are a
      good source for cell therapy. Using a cynomolgus monkey peripheral nervous system
      injury model, we examined the safety and efficacy of Schwann cells induced from
      MSCs as a source for auto-cell transplantation therapy in nerve injury. Serial
      treatment of monkey MSCs with reducing agents and cytokines induced their
      differentiation into cells with Schwann cell properties at a very high ratio.
      Expression of Schwann cell markers was confirmed by both immunocytochemistry and
      reverse transcription-polymerase chain reaction. Induced Schwann cells were used
      for auto-cell transplantation into the median nerve and followed-up for 1year. No
      abnormalities were observed in general conditions. Ki67-immunostaining revealed
      no sign of massive proliferation inside the grafted tube. Furthermore, (18)F
      fluorodeoxygluocose-positron emission tomography scanning demonstrated no
      abnormal accumulation of radioactivity except in regions with expected
      physiologic accumulation. Restoration of the transplanted nerve was corroborated
      by behavior analysis, electrophysiology and histological evaluation. Our results
      suggest that auto-cell transplantation therapy using MSC-derived Schwann cells is
      safe and effective for accelerating the regeneration of transected axons and for
      functional recovery of injured nerves. The practical advantages of MSCs are
      expected to make this system applicable for spinal cord injury and other
      neurotrauma or myelin disorders where the acceleration of regeneration is
      expected to enhance functional recovery.

PMID- 20153321
TI  - The trypanosome Pumilio-domain protein PUF7 associates with a nuclear cyclophilin
      and is involved in ribosomal RNA maturation.
AB  - Proteins with Pumilio RNA binding domains (Puf proteins) are ubiquitous in
      eukaryotes. Some Puf proteins bind to the 3'-untranslated regions of mRNAs,
      acting to repress translation and promote degradation; others are involved in
      ribosomal RNA maturation. The genome of Trypanosoma brucei encodes eleven Puf
      proteins whose function cannot be predicted by sequence analysis. We show here
      that epitope-tagged TbPUF7 is located in the nucleolus, and associated with a
      nuclear cyclophilin-like protein, TbNCP1. RNAi targeting PUF7 reduced trypanosome
      growth and inhibited two steps in ribosomal RNA processing.

PMID- 20153322
TI  - Novel splice variant of mouse insulin2 mRNA: implications for insulin expression.
AB  - Insulin is a secreted peptide that controls glucose homeostasis in mammals, and
      insulin biosynthesis is regulated by glucose at many levels. Rodent insulin is
      encoded by two non-allelic genes. We have identified a novel splice variant of
      the insulin2 gene in mice that constitutes about 75% of total insulin2 mRNA. The
      alternate splicing does not alter the ORF but reduces the 5'UTR by 12 bases. A
      reporter gene containing the novel short 5'UTR, is more efficiently expressed in
      cells, suggesting that alternative splicing of insulin mRNA in mice could result
      in an additional level of regulation in insulin biosynthesis.

PMID- 20153323
TI  - New measures for estimating surface complementarity and packing at protein
      protein interfaces.
AB  - A number of methods exist that use different approaches to assess geometric
      properties like the surface complementarity and atom packing at the protein
      protein interface. We have developed two new and conceptually different measures
      using the Delaunay tessellation and interface slice selection to compute the
      surface complementarity and atom packing at the protein-protein interface in a
      straightforward manner. Our measures show a strong correlation among themselves
      and with other existing measures, and can be calculated in a highly time
      efficient manner. The measures are discriminative for evaluating biological, as
      well as non-biological protein-protein contacts, especially from large protein
      complexes and large-scale structural studies
      (http://pallab.serc.iisc.ernet.in/nip_nsc).

PMID- 20153324
TI  - The protein encoded by the functional steroid receptor RNA activator is a new
      modulator of ER alpha transcriptional activity.
AB  - The steroid receptor RNA activator gene (SRA1) encodes for a functional RNA (SRA)
      as well as a protein (SRAP). While several groups reported on SRA-RNA mechanism
      of action, SRAP exact function remains to be elucidated, mainly due to a lack of
      studies investigating the function of the protein independently of its RNA
      counterpart. Using two independent models to examine its specific functions, SRAP
      was found to enhance estrogen receptor alpha activity in a ligand and response
      element dependent manner. Our data therefore suggest that both transcript and
      protein products of the SRA1 gene co-modulate the transcriptional activity of
      steroid receptors.

PMID- 20153325
TI  - RNA interference-mediated suppression of xanthine dehydrogenase reveals the role
      of purine metabolism in drought tolerance in Arabidopsis.
AB  - We have previously demonstrated that RNA interference-mediated suppression of
      xanthine dehydrogenase (XDH), the rate-limiting enzyme in purine degradation,
      causes defects in the normal growth and development of Arabidopsis thaliana.
      Here, we investigated a possible role for XDH in drought tolerance, since this
      enzyme is also implicated in plant stress responses and acclimatization. When XDH
      suppressed lines were subjected to drought stress, plant growth was markedly
      reduced in conjunction with significantly enhanced cell death and H(2)O(2)
      accumulation. This drought-hypersensitive phenotype was reversed by pretreatment
      with exogenous uric acid, the catalytic product of XDH. These results suggest
      that fully functional purine metabolism plays a role in the Arabidopsis drought
      acclimatization.

PMID- 20153326
TI  - Physiological significance of selective degradation of p62 by autophagy.
AB  - Autophagy is a highly conserved bulk protein degradation pathway responsible for
      the turnover of long-lived proteins, disposal of damaged organelles, and
      clearance of aggregate-prone proteins. Thus, inactivation of autophagy results in
      cytoplasmic protein inclusions, which are composed of misfolded proteins and
      excess accumulation of deformed organelles, leading to liver injury, diabetes,
      myopathy, and neurodegeneration. Although autophagy has been considered non
      selective, growing lines of evidence indicate the selectivity of autophagy in
      sorting vacuolar enzymes and in the removal of aggregate-prone proteins, unwanted
      organelles and microbes. Such selectivity by autophagy enables diverse cellular
      regulations, similar to the ubiquitin-proteasome pathway. In this review, we
      introduce the selective turnover of the ubiquitin- and LC3-binding protein 'p62'
      through autophagy and discuss its physiological significance.

PMID- 20153327
TI  - Heat-shock protein 70 binds to a novel sequence in 5' UTR of tumor suppressor
      SMAR1 and regulates its mRNA stability upon Prostaglandin A2 treatment.
AB  - Here, we report Prostaglandin A2 (PGA2) induced binding of HSP70 to a novel site
      on phi1 SMAR1 5' UTR which stabilizes the wild type transcript and leads to
      subsequent increase in SMAR1 protein levels. SMAR1 mediated cell cycle arrest is
      perturbed in PGA2-treated cells when HSP70 is knocked-down. Contrarily HSP70,
      unlike SMAR1, is overexpressed in breast cancers. We demonstrate that this is
      because of the inability of HSP70 to bind to the phi17 SMAR1 UTR variant which is
      the predominant form in breast cancers.

PMID- 20153329
TI  - Reconstitution of the mitochondrial Hsp70 (mortalin)-p53 interaction using
      purified proteins--identification of additional interacting regions.
AB  - Previous studies have shown that the mammalian mitochondrial 70 kDa heat-shock
      protein (mortalin) can also be detected in the cytosol. Cytosolic mortalin binds
      p53 and by doing so, prevents translocation of the tumor suppressor into the
      nucleus. In this study, we developed a novel binding assay, using purified
      proteins, for tracking the interaction between p53 and mortalin. Our results
      reveal that: (i) P53 binds to the peptide-binding site of mortalin which enhances
      the ability of the former to bind DNA. (ii) An additional previously unknown
      binding site for mortalin exists within the C-terminal domain of p53.

PMID- 20153330
TI  - PINK1 is recruited to mitochondria with parkin and associates with LC3 in
      mitophagy.
AB  - Mutations in PTEN-induced putative kinase 1 (PINK1) cause recessive form of
      Parkinson's disease (PD). PINK1 acts upstream of parkin, regulating mitochondrial
      integrity and functions. Here, we show that PINK1 in combination with parkin
      results in the perinuclear mitochondrial aggregation followed by their
      elimination. This elimination is reduced in cells expressing PINK1 mutants with
      wild-type parkin. Although wild-type PINK1 localizes in aggregated mitochondria,
      PINK1 mutants localization remains diffuse and mitochondrial elimination is not
      observed. This phenomenon is not observed in autophagy-deficient cells. These
      results suggest that mitophagy controlled by the PINK1/parkin pathway might be
      associated with PD pathogenesis.

PMID- 20153328
TI  - Signal transduction to the permeability transition pore.
AB  - The permeability transition pore (PTP) is an inner mitochondrial membrane channel
      that has been thoroughly characterized functionally, yet remains an elusive
      molecular entity. The best characterized PTP-regulatory component, cyclophilin
      (CyP) D, is a matrix protein that favors pore opening. CyP inhibitors, CyP-D null
      animals, and in situ PTP readouts have established the role of PTP as an effector
      mechanism of cell death, and the growing definition of PTP signalling mechanisms.
      This review briefly covers the functional features of the PTP and the role played
      by its dysregulation in disease pathogenesis. Recent progress on PTP modulation
      by kinase/phosphatase signal transduction is discussed, with specific emphasis on
      hexokinase and on the Akt-ERK-GSK3 axis, which might modulate the PTP through CyP
      D phosphorylation.

PMID- 20153331
TI  - Design and characterization of a constitutively open KcsA.
AB  - The molecular nature of the structure responsible for proton sensitivity in KcsA
      has been identified as a charge cluster that surrounds the inner helical bundle
      gate. Here, we show that this proton sensor can be modified to engineer a
      constitutively open form of KcsA, amenable to functional, spectroscopic and
      structural analyses. By combining charge neutralizations for all acidic and basic
      residues in the cluster at positions 25, 117-122 and 124 (but not E118), a mutant
      KcsA is generated that displays constitutively open channel activity up to pH 9.
      The structure of this mutant revealed that full opening appears to be inhibited
      by lattice forces since the activation gate seems to be only on the early stages
      of opening.

PMID- 20153332
TI  - A method for rapid, ligation-independent reformatting of recombinant monoclonal
      antibodies.
AB  - Recombinant monoclonal antibodies currently dominate the protein biologics
      marketplace. The path from target antigen discovery and screening, to a
      recombinant therapeutic antibody can be time-consuming and laborious. We describe
      a set of expression vectors, termed mAbXpress, that enable rapid and sequence
      independent insertion of antibody variable regions into human constant region
      backbones. This method takes advantage of the In Fusion cloning system from
      Clontech, which allows ligation-free, high-efficiency insertion of the variable
      region cassette without the addition of extraneous amino acids. These modular
      vectors simplify the antibody reformatting process during the preliminary
      evaluation of therapeutic or diagnostic candidates. The resulting constructs can
      be used directly for transient or amplifiable, stable expression in mammalian
      cells. The effectiveness of this method was demonstrated by the creation of a
      functional, fully human anti-human CD83 monoclonal antibody.

PMID- 20153333
TI  - Expression and characterization of the chitinases from Serratia marcescens GEI
      strain for the control of Varroa destructor, a honey bee parasite.
AB  - Serratia marcescens GEI strain was isolated from the gut of the workers of
      Chinese honey bee Apis cerana and evaluated in the laboratory for the control of
      Varroa destructor, a parasite of western honey bee A. mellifera. The supernatant
      and the collected proteins by ammonium sulfate from the bacterial cultures showed
      a strong miticidal effect on the female mites, with 100% mite mortality in 5days.
      Heat (100 degrees C for 10min) and proteinase K treatment of the collected
      proteins destroyed the miticidal activity. The improved miticial activity of this
      bacterial strain on chitin medium indicated the involvement of chitinases. The
      expressed chitinases ChiA, ChiB and ChiC1 from S. marcescens GEI by recombinant
      Escherichia coli showed pathogenicity against the mites in the laboratory. These
      chitinases were active in a broad pH range (5-9) and the optimum temperatures
      were between 60 and 75 degrees C. Synergistic effects of ChiA and ChiB on the
      miticidal activity against V. destructor were observed. The workers of both honey
      bee species were not sensitive to the spraying and feeding chitinases. These
      results provided alternative control strategies for Varroa mites, by formulating
      chitinase agents and by constructing transgenetic honey bees.

PMID- 20153334
TI  - Phagocytosis of the protozoan parasite, Marteilia sydneyi, by Sydney rock oyster
      (Saccostrea glomerata) hemocytes.
AB  - QX disease is a fatal disease in Sydney rock oysters caused by the protozoan
      parasite Marteilia sydneyi. The current study investigates the phagocytosis of M.
      sydneyi by Sydney rock oyster hemocytes. It also compares the in vitro phagocytic
      activities of hemocytes from oysters bred for QX disease resistance (QXR) with
      those of wild-type oysters. After ingestion of M. sydneyi, hemocyte granules
      fused with phagosome membranes and the pH of phagosomes decreased. Significantly
      (p=<0.05) more phagosomes in QXR hemocytes showed obvious changes in pH within 40
      min of phagocytosis, when compared with wild-type hemocytes. Phenoloxidase
      deposition was also evident in phagosomes after in vitro phagocytosis. Most
      importantly, ingested and melanised M. sydneyi were detected in vivo among
      hemocytes from infected oysters. Overall, the data suggest that Sydney rock
      oyster hemocytes can recognise and phagocytose M. sydneyi, and that resistance
      against QX disease may be associated with enhanced phagolysosomal activity in QXR
      oysters.

PMID- 20153335
TI  - Beneficial effects of exercise training after myocardial infarction require full
      eNOS expression.
AB  - Exercise training attenuates left ventricular (LV) dysfunction after myocardial
      infarction (MI). It could be speculated that these effects of exercise are
      mediated by increased endothelial NO synthase (eNOS) activity. In the present
      study we tested the hypothesis that eNOS plays a critical role in the exercise
      induced amelioration of LV dysfunction after MI. MI or sham was induced in eNOS(
      /-), eNOS(+/-) and eNOS(+/+) mice. After 8 weeks of voluntary wheel running
      (approximately 7 km/day in all groups) or sedentary housing, global cardiac
      function was determined in vivo and (immuno)histochemistry was performed to
      assess cardiomyocyte size, fibrosis, capillary density and apoptosis in remote
      myocardium. At baseline eNOS(-/-) mice had higher mean aortic pressure compared
      to eNOS(+/-) and eNOS(+/+) mice, but had normal global cardiac function. MI
      resulted in marked LV remodeling, including cardiomyocyte hypertrophy and a
      reduction in capillary density, increased fibrosis and apoptosis, as well as LV
      systolic and diastolic dysfunction to the same extent in all genotypes. In
      eNOS(+/+) MI mice exercise abolished fibrosis and apoptosis in the remote
      myocardium, attenuated LV systolic dysfunction and ameliorated pulmonary
      congestion. These beneficial effects were lost in eNOS(+/-) and eNOS(-/-) mice,
      while LV systolic dysfunction and pulmonary congestion in eNOS(+/-) mice were
      exacerbated by exercise. In conclusion, the beneficial effects of exercise after
      MI on LV remodeling and dysfunction depend critically on endogenous eNOS. The
      observation that the lack of one eNOS allele is sufficient to negate all
      beneficial effects of exercise, strongly suggests that exercise depends on full
      eNOS expression.

PMID- 20153336
TI  - Solution structure of Gfi-1 zinc domain bound to consensus DNA.
AB  - Gfi-1 is a crucial transcriptional repressor for the precise regulation of cell
      proliferation and differentiation in hematopoiesis. Recently, this protein has
      also been demonstrated to be capable of restricting the proliferation of
      hematopoietic stem cells, a process that appears to be vital for the long-term
      competency of hematopoietic stem cells. These two seemingly opposite outcomes of
      regulation are likely to arise from its interactions with a variety of cellular
      partners. Such interactions can directly affect the genes that Gfi-1 recognizes
      through its DNA binding zinc-finger domain. In this work, we report the
      determination of the solution structure of Gfi-1 zinc fingers 3-5 in complex with
      a 16-mer consensus DNA using multidimensional NMR method. Unlike a proposed minor
      groove binding model based on methylation interference experiments, our structure
      clearly shows that Gfi-1 zinc fingers 3-5 bind into the major groove of the
      target DNA reminiscent of canonical C(2)H(2) zinc-finger domains. The fourth and
      fifth zinc fingers recognize the AATC core sequence by forming base-specific
      hydrogen bonds between the side chains of Asn382, Gln379, and Asp354 and the
      bases of the invariant adenines and cytosine. Overall, the current work provides
      valuable insight into the structural determinants for DNA binding specificity, in
      particular for the TCA triplet that has not been observed in any other structures
      of zinc finger-DNA complexes, as well as molecular rationales for a naturally
      occurring mutation that causes acute myeloid leukemia.

PMID- 20153337
TI  - Dynamical phase coexistence: a simple solution to the "savanna problem".
AB  - We introduce the concept of dynamical phase coexistence to provide a simple
      solution for a long-standing problem in theoretical ecology, the so-called
      "savanna problem". The challenge is to understand why in savanna ecosystems trees
      and grasses coexist in a robust way with large spatiotemporal variability. We
      propose a simple model, a variant of the contact process (CP), which includes two
      key extra features: varying external (environmental/rainfall) conditions and tree
      age. The system fluctuates locally between a woodland and a grassland phase,
      corresponding to the active and absorbing phases of the underlying pure contact
      process. This leads to a highly variable stable phase characterized by patches of
      the woodland and grassland phases coexisting dynamically. We show that the mean
      time to tree extinction under this model increases as a power-law of system size
      and can be of the order of 10,000,000 years in even moderately sized savannas.
      Finally, we demonstrate that while local interactions among trees may influence
      tree spatial distribution and the order of the transition between woodland and
      grassland phases, they do not affect dynamical coexistence. We expect dynamical
      coexistence to be relevant in other contexts in physics, biology or the social
      sciences.

PMID- 20153338
TI  - Essential molecular functions associated with the circular code evolution.
AB  - A circular code is a set of trinucleotides allowing the reading frames in genes
      to be retrieved locally, i.e. anywhere in genes and in particular without start
      codons, and automatically with a window of few nucleotides. In 1996, a common
      circular code, called X, was identified in large populations of eukaryotic and
      prokaryotic genes. Hence, it is believed to be an ancestral structural property
      of genes. A new computational approach based on comparative genomics is developed
      to identify essential molecular functions associated with circular codes. It is
      based on a quantitative and sensitive statistical method (FPTF) to identify three
      permuted trinucleotide sets in the three frames of genes, a flower automaton
      algorithm to determine if a trinucleotide set is a circular code or not, and an
      integrated Gene Ontology and Taxonomy (iGOT) database. By carrying out automatic
      circular code analyses on a huge number of gene populations where each population
      is associated with a particular molecular function, it identifies 266 gene
      populations having circular codes close to X. Surprisingly, their molecular
      functions include 98% of those covered by the essential genes of the DEG database
      (Database of Essential Genes). Furthermore, three trinucleotides GTG, AAG and
      GCG, replacing three trinucleotides of the code X and called "evolutionary"
      trinucleotides, significantly occur in these 266 gene populations. Finally, a new
      method developed to analyse and quantify the stability of a set of trinucleotides
      demonstrates that these evolutionary trinucleotides are associated with a
      significant increase of the stability of the common circular code X. Indeed, its
      stability increases from the 1502th rank to the 16th rank after the replacement
      of the three evolutionary trinucleotides among 9920 possible trinucleotide
      replacement sets.

PMID- 20153339
TI  - Role of endothelial cell-selective adhesion molecule in hematogeneous metastasis.
AB  - The spread of malignant cells from a localized tumor is thought to be directly
      related to the number of microvessels in the tumor. The endothelial cell
      selective adhesion molecule (ESAM) is a member of the immunoglobulin superfamily
      that mediates homophilic interactions between endothelial cells. Previous studies
      have indicated that ESAM regulates angiogenesis in the primary tumor growth and
      endothelial permeability. In this study, we aimed to further elucidate the role
      of ESAM in tumor metastasis through angiogenic processes. ESAM expression was
      higher in hypervascular metastatic tumor tissues than in normal tissues in human
      lungs. Cell culture studies found that conditioned medium from B16F10 melanoma
      cells increased ESAM expression in endothelial cells and promoted endothelial
      migration and tube formation. The B16F10 medium-induced endothelial migration and
      tube formation were significantly attenuated when ESAM was downregulated by siRNA
      transfection. Intravenous injection of B16F10 cells into ESAM+/+ and ESAM-/- mice
      for comparison of metastatic potential resulted in the number of metastatic lung
      nodules in ESAM-/- mice being 83% lower than of those in ESAM+/+ mice. The
      microvascular density in the tumor was also lower in ESAM-/- than in ESAM+/+
      mice. These findings indicate that ESAM regulates tumor metastasis through
      endothelial cell migration and tube formation in metastatic nodules. Inhibition
      of ESAM may therefore inhibit tumor metastasis by inhibiting the angiogenic
      processes.

PMID- 20153341
TI  - Effects of serotonin (5-HT)2 receptor ligands on depression-like behavior during
      nicotine withdrawal.
AB  - A pronounced withdrawal syndrome including depressed mood prevents cigarette
      smoking cessation. We tested if blockade or activation of serotonin (5-HT)(2)
      receptors affected the time of immobility (as an indirect measure of depression
      like behavior) in naive animals and in those withdrawn from chronic nicotine in
      the forced swim test (FST). The antidepressant imipramine was used as a control.
      In the FST, the selective 5-HT(2A) receptor antagonist M100,907 (1-2 mg/kg, but
      not 0.5 mg/kg), the selective 5-HT(2C) receptor antagonist SB 242,084 (0.3-1
      mg/kg, but not 0.1 mg/kg), the 5-HT(2C) receptor agonists Ro 60-0175 (10 mg/kg,
      but not 3 mg/kg) and WAY 163,909 (1.5-10 mg/kg, but not 0.75 mg/kg) as well as
      imipramine (30 mg/kg, but not 15 mg/kg) decreased the immobility time while the
      non-selective 5-HT(2) receptor agonist DOI (0.1-1 mg/kg) was inactive in naive
      rats. We found an increase in immobility time in rats that were withdrawn from
      nicotine exposure after 5 days of chronic nicotine treatment. This effect
      increased from day 1 until day 10 following withdrawal of nicotine, with maximal
      withdrawal effects on day 3. M100,907 (1 mg/kg), SB 242,084 (0.3 mg/kg), Ro 60
      0175 (3 mg/kg), WAY 163,909 (0.75-1.5 mg/kg) and imipramine (15-30 mg/kg)
      shortened the immobility time in rats that had been removed from nicotine
      exposure for 3 days. Locomotor activity studies indicated that the effects of SB
      242,084 might have been non-specific, as we noticed enhanced basal locomotion in
      naive rats. This data set demonstrates that 5-HT(2A) receptor antagonist and 5
      HT(2C) receptor agonists exhibited effects similar to antidepressant drugs and
      abolished the depression-like effects in nicotine-withdrawn rats. These drugs
      should be considered as adjuncts to smoking cessation therapy, to ameliorate
      abstinence-induced depressive symptoms.

PMID- 20153340
TI  - Pharmacokinetics and bioactivity of glial cell line-derived factor (GDNF) and
      neurturin (NTN) infused into the rat brain.
AB  - Convection-enhanced delivery (CED) of GDNF and NTN was employed to determine the
      tissue clearance of these factors from the rat striatum and the response of the
      dopaminergic system to a single infusion. Two doses of GDNF (15 and 3 microg) and
      NTN (10 microg and 2 microg) were infused into the rat striatum. Animals were
      euthanized 3, 7, 14, 21, and 28 days post-infusion. Brains were processed for
      ELISA, HPLC, and immunohistochemistry (IHC). Both doses of the infused GDNF
      resulted in a sharp increase in striatal GDNF levels followed by a rapid decrease
      between day 3 and 7. Interestingly, IHC revealed GDNF in the septum and the base
      of the brain 14 days after GDNF administration. Dopamine (DA) turnover was
      significantly increased in a dose-dependent manner for more than 7 days after a
      single GDNF infusion. NTN persisted in the brain for at least two weeks longer
      than GDNF. It also had more persistent effects on DA turnover, probably due to
      its precipitation in the brain at neutral pH after infusion. Our data suggest
      that daily or continuous dosing may not be necessary for delivering growth
      factors into the CNS.

PMID- 20153342
TI  - Microglia signaling as a target of donepezil.
AB  - Donepezil is a reversible and noncompetitive cholinesterase inhibitor. The drug
      is considered as a first-line treatment in patients with mild to moderate
      Alzheimer's disease. Recently, anti-inflammatory and neuroprotective effects of
      the drug have been reported. "Cholinergic anti-inflammation pathway" has major
      implications in these effects. Here, we present evidence that donepezil at 5-20
      microM directly acts on microglial cells to inhibit their inflammatory
      activation. Our conclusion is based on the measurement of nitric oxide and
      proinflammatory mediators using purified microglia cultures and microglia cell
      lines: donepezil attenuated microglial production of nitric oxide and tumor
      necrosis factor (TNF)-alpha, and suppressed the gene expression of inducible
      nitric oxide synthase, interleukin-1 beta, and TNF-alpha. Subsequent studies
      showed that donepezil inhibited a canonical inflammatory NF-kappaB signaling.
      Microglia/neuroblastoma coculture and animal experiments supported the anti
      inflammatory effects of donepezil. Based on the studies using nicotinic
      acetylcholine receptor antagonists, the donepezil inhibition of microglial
      activation was independent of acetylcholine and its receptor. Thus, inflammatory
      activation signaling of microglia may be one of the direct targets of donepezil
      in the central nervous system. It should be noted, however, that there is a large
      gap between the therapeutic dose of the drug used clinically and the
      concentration of the drug that exerts the direct action on microglial cells.

PMID- 20153343
TI  - Experience-dependent neural specialization during infancy.
AB  - The ability to recognize the difference among faces of another race or species
      declines from 6 to 9 months of age. During this time, perceptual biases are
      formed, leading to lasting deficits in recognizing individuals of other races and
      species. However, little is known about how early infant experience shapes the
      neural structures underlying face processing. Here we found neural
      specialization, in infants who received 3 months of training with six
      individually labeled monkey faces. However, neural specialization was not found
      after an equal amount of training with the same six faces labeled at the category
      level (i.e., all faces labeled "monkey") or when infants were exposed to faces
      without labels. These results suggest that neural specialization for faces
      requires learning at the individual level during infancy.

PMID- 20153344
TI  - The 7-hydroxylation of dehydroepiandrosterone in rat brain.
AB  - Dehydroepiandrosterone (DHEA) is an important neurosteroid with multiple
      functions in the central nervous system including neuroprotection. How DHEA
      exerts its neuroprotection function has not been fully elucidated. One possible
      mechanism is via its active metabolites, 7alpha-OH DHEA and 7beta-OH DHEA. The
      purpose of this research is to understand how DHEA is metabolized to 7alpha-OH
      DHEA and 7beta-OH DHEA by brain tissue. DHEA was incubated with rat brain
      microsomes and mitochondria and the 7alpha-OH DHEA and 7beta-OH DHEA formed by
      these fractions were analyzed by LC/MS. For the first time, we observed that DHEA
      could be metabolized to 7alpha-OH DHEA and 7beta-OH DHEA in mitochondria but the
      formation of 7alpha-OH DHEA and 7beta-OH DHEA demonstrated different enzymatic
      kinetic properties. Adding NADPH, an essential cofactor, to mitochondria
      incubation mixtures increased only the formation of 7alpha-OH DHEA, but not that
      of 7beta-OH DHEA. Addition of estradiol to the incubation mixtures inhibited only
      the formation of 7alpha-OH DHEA, but not that of 7beta-OH DHEA. Western blot
      analysis showed that both microsomes and mitochondria contained cytochrome P450
      7B. We also found that 7alpha-OH DHEA could be converted to 7beta-OH DHEA by rat
      brain homogenates. Our data suggest that 7alpha-OH DHEA and 7beta-OH DHEA are
      formed by different enzymes and that 7beta-OH DHEA can be formed from both DHEA
      and 7alpha-OH DHEA, although the overall level of 7beta-OH DHEA was very low.

PMID- 20153345
TI  - Autophagy is the predominant process induced by arsenite in human lymphoblastoid
      cell lines.
AB  - Arsenic is a widespread environmental toxicant with a diverse array of molecular
      targets and associated diseases, making the identification of the critical
      mechanisms and pathways of arsenic-induced cytotoxicity a challenge. In a variety
      of experimental models, over a range of arsenic exposure levels, apoptosis is a
      commonly identified arsenic-induced cytotoxic pathway. Human lymphoblastoid cell
      lines (LCL) have been used as a model system in arsenic toxicology for many
      years, but the exact mechanism of arsenic-induced cytotoxicity in LCL is still
      unknown. We investigated the cytotoxicity of sodium arsenite in LCL 18564 using a
      set of complementary markers for cell death pathways. Markers indicative of
      apoptosis (phosphatidylserine externalization, PARP cleavage, and sensitivity to
      caspase inhibition) were uniformly negative in arsenite exposed cells.
      Interestingly, electron microscopy, acidic vesicle fluorescence, and expression
      of LC3 in LCL 18564 identified autophagy as an arsenite-induced process that was
      associated with cytotoxicity. Autophagy, a cellular programmed response that is
      associated with both cellular stress adaptation as well as cell death appears to
      be the predominant process in LCL cytotoxicity induced by arsenite. It is
      unclear, however, whether LCL autophagy is an effector mechanism of arsenite
      cytotoxicity or alternatively a cellular compensatory mechanism. The ability of
      arsenite to induce autophagy in lymphoblastoid cell lines introduces a
      potentially novel mechanistic explanation of the well-characterized in vitro and
      in vivo toxicity of arsenic to lymphoid cells.

PMID- 20153346
TI  - The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is
      associated with S-nitrosoglutathione-induced apoptosis in human endothelial
      cells.
AB  - The pathophysiological relevance of S-nitrosoglutathione (GSNO)-induced
      endothelial cell injury remains unclear. The main objective of this study was to
      elucidate the molecular mechanisms of GSNO-induced oxidative stress in
      endothelial cells. Morphological evaluation through DAPI staining and propidium
      iodide (PI) flow cytometry was used to detect apoptosis. In cultured EA.hy926
      endothelial cells, exposure to GSNO led to a time- and dose-dependent apoptotic
      cascade. When intracellular reactive oxygen species (ROS) production was measured
      in GSNO-treated cells with the fluorescent probes 5-(and-6)-carboxy-2',7'
      dichlorofluorescein diacetate, we observed elevated ROS levels and a concomitant
      loss in mitochondrial membrane potential, indicating that GSNO-induced death
      signaling is mediated through a ROS-mitochondrial pathway. Importantly, we found
      that peroxynitrite formation and Omi/HtrA2 release from mitochondria were
      involved in this phenomenon, whereas changes of death-receptor dependent
      signaling were not detected in the same context. The inhibition of NADPH oxidase
      activation and Omi/HtrA2 by a pharmacological approach provided significant
      protection against caspase-3 activation and GSNO-induced cell death, confirming
      that GSNO triggers the death cascade in endothelial cells in a mitochondria
      dependent manner. Taken together, our results indicate that ROS overproduction
      and loss of mitochondrial Omi/HtrA2 play a pivotal role in reactive nitrogen
      species-induced cell death, and the modulation of these pathways can be of
      significant therapeutic benefit.

PMID- 20153347
TI  - Acrolein increases 5-lipoxygenase expression in murine macrophages through
      activation of ERK pathway.
AB  - Episodic exposure to acrolein-rich pollutants has been linked to acute myocardial
      infarction, and 5-lipoxygenase (5-LO) is involved in the production of matrix
      metalloproteinase-9 (MMP-9), which destabilizes atherosclerotic plaques. Thus,
      the present study determined the effect of acrolein on 5-LO/leukotriene B(4)
      (LTB(4)) production in murine macrophages. Stimulation of J774A.1 cells with
      acrolein led to increased LTB(4) production in association with increased 5-LO
      expression. Acrolein-evoked 5-LO expression was blocked by pharmacological
      inhibition of the ERK pathway, but not by inhibitors for JNK and p38 MAPK
      pathways. In line with these results, acrolein exclusively increased the
      phosphorylation of ERK among these MAPK, suggesting a role for the ERK pathway in
      acrolein-induced 5-LO expression with subsequent production of LTB(4). Among the
      receptor tyrosine kinases including epidermal growth factor receptor (EGFR) and
      platelet derived growth factor receptor (PDGFR), acrolein-evoked ERK
      phosphorylation was attenuated by AG1478, an EGFR inhibitor, but not by AG1295, a
      PDGFR inhibitor. In addition, acrolein-evoked 5-LO expression was also inhibited
      by inhibition of EGFR pathway, but not by inhibition of PDGFR pathway. These
      observations suggest that acrolein has a profound effect on the 5-LO pathway via
      an EGFR-mediated activation of ERK pathway, leading to acute ischemic syndromes
      through the generation of LTB(4), subsequent MMP-9 production and plaque rupture.

PMID- 20153348
TI  - The membrane estrogen receptor GPR30 mediates cadmium-induced proliferation of
      breast cancer cells.
AB  - Cadmium (Cd) is a nonessential metal that is dispersed throughout the
      environment. It is an endocrine-disrupting element which mimics estrogen, binds
      to estrogen receptor alpha (ERalpha), and promotes cell proliferation in breast
      cancer cells. We have previously published that Cd promotes activation of the
      extracellular regulated kinases, erk-1 and -2 in both ER-positive and ER-negative
      human breast cancer cells, suggesting that this estrogen-like effect of Cd is not
      associated with the ER. Here, we have investigated whether the newly appreciated
      transmembrane estrogen receptor, G-protein coupled receptor 30 (GPR30), may be
      involved in Cd-induced cell proliferation. Towards this end, we compared the
      effects of Cd in ER-negative human SKBR3 breast cancer cells in which endogenous
      GPR30 signaling was selectively inhibited using a GPR30 interfering mutant. We
      found that Cd concentrations from 50 to 500 nM induced a proliferative response
      in control vector-transfected SKBR3 cells but not in SKBR3 cells stably
      expressing interfering mutant. Similarly, intracellular cAMP levels increased
      about 2.4-fold in the vector transfectants but not in cells in which GPR30 was
      inactivated within 2.5 min after treatment with 500 nM Cd. Furthermore, Cd
      treatment rapidly activated (within 2.5 min) raf-1, mitogen-activated protein
      kinase kinase, mek-1, extracellular signal regulated kinases, erk-1/2, ribosomal
      S6 kinase, rsk, and E-26 like protein kinase, elk, about 4-fold in vector
      transfectants. In contrast, the activation of these signaling molecules in SKBR3
      cells expressing the GPR30 mutant was only about 1.4-fold. These results
      demonstrate that Cd-induced breast cancer cell proliferation occurs through GPR30
      mediated activation in a manner that is similar to that achieved by estrogen in
      these cells.

PMID- 20153349
TI  - Evaluation of two different metabolic hypotheses for dichloromethane toxicity
      using physiologically based pharmacokinetic modeling for in vivo inhalation gas
      uptake data exposure in female B6C3F1 mice.
AB  - Dichloromethane (DCM, methylene chloride) is a lipophilic volatile compound
      readily absorbed and then metabolized to several metabolites that may lead to
      chronic toxicity in different target organs. Physiologically based
      pharmacokinetic (PBPK) models are useful tools for calculation of internal and
      target organ doses of parent compound and metabolites. PBPK models, coupled with
      in vivo inhalation gas-uptake data, can be useful to estimate total metabolism.
      Previously, such an approach was used to make predictions regarding the
      metabolism and to make subsequent inferences of DCM's mode of action for
      toxicity. However, current evidence warrants re-examination of this approach. The
      goal of this work was to examine two different hypotheses for DCM metabolism in
      mice. One hypothesis describes two metabolic pathways: one involving cytochrome
      P450 2E1 (CYP2E1) and a second glutathione (GSH). The second metabolic hypothesis
      describes only one pathway mediated by CYP2E1 that includes multiple binding
      sites. The results of our analysis show that the in vivo gas-uptake data fit both
      hypotheses well and the traditional analysis of the chamber concentration data is
      not sufficient to distinguish between them. Gas-uptake data were re-analyzed by
      construction of a velocity plot as a function of increasing DCM initial
      concentration. The velocity (slope) analysis revealed that there are two
      substantially different phases in velocity, one rate for lower exposures and a
      different rate for higher exposures. The concept of a "metabolic switch," namely
      that due to conformational changes in the enzyme after one site is occupied - a
      different metabolic rate is seen - is also consistent with the experimental data.
      Our analyses raise questions concerning the importance of GSH metabolism for DCM.
      Recent research results also question the importance of this pathway in the
      toxicity of DCM. GSH-related DNA adducts were not formed after in vivo DCM
      exposure in mice and DCM-induced DNA damage has been detected in human lung
      cultures without GSH metabolism. In summary, a revised/updated metabolic
      hypothesis for DCM has been examined using in vivo inhalation data in mice
      combined with PBPK modeling that is consistent with up-to-date models of the
      active site for CYP2E1 and suggests that this pathway is the major metabolizing
      pathway for DCM metabolism.

PMID- 20153350
TI  - Characterization of a novel live attenuated infectious bronchitis virus vaccine
      candidate derived from a Korean nephropathogenic strain.
AB  - A nephropathogenic K2/01 strain of infectious bronchitis virus (IBV) was
      attenuated by 170 serial passages in embryonated chicken eggs for possible use as
      a future IBV vaccine strain. High-growth properties and narrow tissue tropisms
      (limited replication in respiratory tracts) were achieved by the adaptation
      process. Unlike the parent strain, the attenuated strain (K2p170) was safe in day
      old specific-pathogen-free chicks since replication of the virus did not induce
      mortality and nephritis, and rarely induced histological changes in the trachea
      and kidney after intraocular administration. In day-old broilers, even though
      coarse spray administration of K2p170 induced clinical signs, ciliostasis, and
      histopathological lesions in the trachea and the kidney, they were all comparable
      to birds vaccinated with commercial H120 vaccine. Despite restriction of viral
      replication in the respiratory tract, K2p170 elicited the production of antiserum
      with a neutralization index of 4.5. K2p170 provided almost complete protection
      against both two distinct subgroups of Korean nephropathogenic strain (KM91-like
      and QX-like subgroup). Furthermore, K2p170 provided significantly greater cross
      protection against two heterologous strains (Massachusetts and Korean respiratory
      strain) than those conferred by the commercial H120 vaccine. K2p170 also had no
      virulence reversion after five back passages in chickens. In conclusion, K2p170
      exhibits a fine balance between attenuation and immunogenicity, possesses cross
      protective efficacy, and merits further investigation as a potential live vaccine
      as an alternative means of protection against the recently emergent
      nephropathogenic IBV infection in many Eurasian countries.

PMID- 20153351
TI  - Estimating the influenza vaccine effectiveness in elderly on a yearly basis using
      the Spanish influenza surveillance network--pilot case-control studies using
      different control groups, 2008-2009 season, Spain.
AB  - We conducted a case-control and screening method studies to estimate influenza
      vaccine effectiveness (IVE) in the age group >or=65 years, based on the Spanish
      Influenza Sentinel Surveillance System (SISSS). Cases (influenza laboratory
      confirmed) were compared to influenza-negative ILI patients (test-negative) and
      patients without ILI since the beginning of the season (non-ILI). For the
      screening method, cases' vaccination coverage was compared to the vaccination
      coverage of the GPs' catchment population. The results suggested a protective
      effect of the vaccine against laboratory-confirmed influenza in elderly in 2008
      2009. The screening method and the test-negative control designs enable
      estimating IVE using exclusively SISSS data.

PMID- 20153352
TI  - Evaluation of Southern Hemisphere influenza vaccine recommendations.
AB  - In 1999, the World Health Organization switched from annual to semi-annual
      recommendations for influenza vaccine composition. We compared the antigenic
      match between recommendations and circulating viruses before and after 1999, in
      the Northern and Southern Hemispheres. Vaccine match proportion for A/H3N2
      viruses increased from 31% to 59% in the Southern Hemisphere (P<0.05), and is now
      comparable to that in the Northern Hemisphere. Vaccine match for influenza B
      decreased from approximately 100% to 33-54% in both hemispheres (P<0.05),
      following the unexpected resurgence of influenza B/Victoria in 1997. No estimate
      was available for influenza A/H1N1. We conclude that semi-annual vaccine
      recommendations are useful overall and discuss potential ways forward, including
      a recommendation for the improvement of vaccination policy and influenza
      surveillance in tropical areas.

PMID- 20153353
TI  - Porcine lactoferrin administration enhances peripheral lymphocyte proliferation
      and assists infectious bursal disease vaccination in native chickens.
AB  - The purpose of this study was to investigate the effects of dietary
      supplementation with recombinant porcine lactoferrin (rPLF) produced by yeast
      culture on peripheral lymphocyte proliferation and serum antibody titers in
      chickens vaccinated against the infectious bursal disease (IBD) virus. Treatment
      groups were fed with rPLF powder in their diet (2.0%, w/w), and the IBD vaccine
      was administrated at 1 and 3 weeks of age. At 8, 12, and 16 weeks after
      vaccination, serum IBD antibody titers were measured via the micro-method and T
      cell proliferation rates were evaluated. In gene expression analyses, rPLF
      treated chicken peripheral T lymphocytes were stimulated with concanavalin A
      (ConA) for 24h. The mRNA expression levels of interleukin-2 (IL-2), interferon
      gamma (IFN-gamma), interleukin-4 (IL-4), and interleukin-12 (IL-12) were
      determined using a semi-quantitative RT-PCR assay. The results revealed that the
      rPLF additive led to significant increases in serum IgG and IBD-specific antibody
      titers (P<0.05). The rPLF administration significantly increased chicken
      intestinal villous lengths and also enhanced the expression of IFN-gamma and IL
      12 in chicken T lymphocytes. These data suggest that rPLF enhances cell-mediated
      immunity and augment the ability of IBD vaccination to benefit chicken industry
      in disease resistance.

PMID- 20153354
TI  - Control of Salmonella Enteritidis and Salmonella Gallinarum in birds by using
      live vaccine candidate containing attenuated Salmonella Gallinarum mutant strain.
AB  - The ideal live vaccine to control Salmonella in commercial chicken flocks should
      engender protection against various strains. The purpose of the present study was
      to confirm the attenuation of a Salmonella Gallinarum (SG) mutant strain with
      deletion on genes cobS and cbiA, that are involved in the biosynthesis of
      cobalamin. Furthermore, evaluate its use as a live vaccine against Salmonella.
      For the evaluation of the vaccine efficacy, two experiments were conducted
      separately. Birds from a commercial brown line of chickens were used to perform
      challenge with SG wild type strain and birds from a commercial white line of
      chickens were used to perform challenge with Salmonella Enteritidis (SE) wild
      type strain. In both experiments, the birds were separated in three groups (A, B
      and C). Birds were orally vaccinated with the SG mutant as the following
      programme: group A, one dose at 5 days of age; group B, one dose at 5 days of age
      and a second dose at 25 days of age; and group C, birds were kept unvaccinated as
      controls. At 45 days of age, birds from all groups, including the control, were
      challenged orally by SG wild type (brown line) or SE wild type (white line).
      Lastly, another experiment was performed to evaluate the use of the SG mutant
      strain to prevent caecal colonization by SE wild type on 1-day-old broiler
      chicks. Mortality and systemic infection by SG wild type strain were assessed in
      brown chickens; faecal shedding and systemic infection by SE wild type were
      assessed in white chickens and caecal colonization was assessed in broiler
      chicks. Either vaccination with one or two doses of SG mutant, were capable to
      protect brown chickens against SG wild type. In the experiment with white
      chickens, only vaccination with two doses of SG mutant protected the birds
      against challenge with SE wild type. Although, SG mutant could not prevent caecal
      colonization in 1-day-old broiler chicks by the challenge strain SE wild type.
      Overall, the results indicated that SG mutant is a promising Salmonella live
      vaccine candidate that demonstrated good efficacy to control the infection by two
      serotypes of major importance to the poultry industry.

PMID- 20153355
TI  - Multistability property in cardiac ionic models of mammalian and human
      ventricular cells.
AB  - The underlying mechanisms of irregular cardiac rhythms are still poorly
      understood. Many experimental and modeling studies are aimed at identifying
      factors which cause cardiac arrhythmias. However, a lack of understanding of
      heart rhythm dynamical properties makes it difficult to uncover precise
      mechanisms of electrical instabilities, and hence to predict the onset of heart
      rhythm disorders. We review and compare the existing methods of studying cardiac
      dynamics, including restitution protocol (S1-S2), dynamic restitution protocol
      and multistability test protocol (S1-CI-S2). We focus on cardiac cell dynamics to
      elucidate regularities of heart rhythm. We demonstrate the advantages of our
      newly proposed systematic approach of analysis of cardiac cell dynamics using
      mammalian Luo Rudy 1991 and human ventricular Ten Tusscher 2006 single cell
      models under healthy and diseased conditions such as altered K(+) or Ca(2+)
      related currents. We investigate the role of ionic properties and the shape of an
      action potential on the nonlinear dynamics of electrical processes in
      periodically stimulated cardiac cells. We show the existence of multistability
      property for human ventricular cells. Moreover, the multistability is proposed to
      be an intrinsic property of cardiac cells, and is also suggested to be one of the
      mechanisms which could underlie the sudden triggering of life-threatening
      ventricular arrhythmias in the human heart.

PMID- 20153356
TI  - Context-dependent sensitization to ethanol in zebrafish (Danio rerio).
AB  - One of the most robust and readily measurable effects of moderate doses of
      ethanol on zebrafish behavior is locomotor hyperactivity. Two experiments were
      designed to examine the effects of repeated exposures to ethanol on ethanol
      induced locomotor hyperactivity, and to determine whether these effects are
      context-dependent. Adult, wild-type zebrafish were given repeated exposure to
      ethanol in the presence of one contextual stimulus (A), while exposed to water in
      the presence of a second contextual stimulus (B). Exposure to ethanol
      consistently induced locomotor hyperactivity. After repeated exposures, animals
      tested with ethanol in the ethanol-paired context (A) showed sensitization of
      locomotor activity. When tested with ethanol in the unpaired context (B),
      however, sensitization was not observed. When tested in the absence of ethanol,
      there were no differences in responding to the paired and unpaired stimuli. This
      is the first demonstration of ethanol-induced locomotor sensitization in
      zebrafish. Moreover, this sensitization was context-specific, indicating that
      learning can modify drug-induced behaviors in zebrafish.

PMID- 20153357
TI  - Dose-dependent dissociable effects of haloperidol on locomotion, appetitive
      responses, and consummatory behavior in water-deprived rats.
AB  - We studied whether a cascade of different phases of ingestive behavior were
      governed by different doses of the dopamine D2 receptor system. A wide spectrum
      of doses (0, 0.025, 0.05, 0.1, 0.2, and 0.4mg/kg) of a D2 receptor antagonist,
      haloperidol, were administered to 6 groups of water-deprived rats. 45min
      following administration of the drug a 15min water intake session was allowed to
      assess the effect on (a) locomotion, (b) appetitive response and (c) consummatory
      responses. The procedure was repeated for 5days. RESULTS: The doses of 0.025 to
      0.1mg/kg had no effects on any measured behavior compared with the control group.
      The 0.2mg/kg dose induced catalepsy during sessions 3 and 5 and impaired
      consummatory (decreased lick numbers and intake volume) behaviors during sessions
      1-5. The 0.4mg/kg dose affected appetitive behavior (increased latency to contact
      the water tube) during session 2 and consummatory behavior during all five water
      sessions. The 0.2mg/kg dose appeared to dissociate appetitive and consummatory
      behavior, and the 0.4mg/kg dose locomotor activity and motivational behavior
      (including consummatory and appetitive responses). These results, that the three
      elements of ingestive behavior (locomotion, appetitive responses, and
      consummatory behavior) have different sensitivity to haloperidol, suggest that
      separable D2 mechanisms are involved in governing the ingestive behavior.

PMID- 20153358
TI  - Vaccinating adolescent girls against human papillomavirus-Who decides?

PMID- 20153359
TI  - How equitable are colorectal cancer screening programs which include FOBTs? A
      review of qualitative and quantitative studies.
AB  - OBJECTIVE: To review published literature on the equity of participation in
      colorectal cancer screening amongst different population subgroups, in addition
      to identifying factors identified as barriers and facilitators to equitable
      screening. Studies were included in the review if they included FOBT as at least
      one of the screening tests. METHOD: Relevant published articles were identified
      through systematic electronic searches of selected databases and the examination
      of the bibliographies of retrieved articles. Studies of the association with
      colorectal cancer screening test participation, barriers to equitable
      participation in screening, and studies examining interventional actions to
      facilitate screening test participation were included. Data extraction and
      analysis was undertaken using an approach to the synthesis of qualitative and
      quantitative studies called Realist Review. RESULTS: Sixty-three articles were
      identified that met the inclusion criteria. SES status, ethnicity, age and gender
      have been found as predictors of colorectal cancer screening test participation.
      This review also found that the potential for equitable cancer screening test
      participation may be hindered by access barriers which vary amongst population
      sub-groups. CONCLUSION: This review provides evidence of horizontal inequity in
      colorectal cancer screening test participation, but limited understanding of the
      mechanism by which it is sustained, and few evidence-based solutions.

PMID- 20153360
TI  - Knowledge about health benefits of vitamin D in Queensland Australia.

PMID- 20153361
TI  - Using accelerometers and GPS units to identify the proportion of daily physical
      activity located in parks with playgrounds in New Zealand children.
AB  - OBJECTIVE: To identify the proportion of children's physical activity occurring
      in public parks with playgrounds. METHODS: Children (n=184) aged 5 to 10 years
      were recruited from schools located in two low socio-economic status communities
      in Dunedin, New Zealand. Accelerometers (Actigraph GT1M) and global positioning
      system units (Globalsat DG-100) were used to quantify and identify where physical
      activity had occurred over a 7-day period. Cross-sectional data were collected
      October to December 2007 (southern hemisphere spring) and the child's height and
      weight were measured at school. RESULTS: At least 84% of participants had
      accelerometer and global positioning system data available for five or more
      hourly periods per day, for at least 4 days. Overall, 1.9% of recorded activity
      took place at city parks (95% confidence interval: 1.4, 2.4), although this was
      2.7% (95% confidence intervals: 0.7, 4.6) among obese children. CONCLUSIONS:
      Accelerometers and GPS data was able to be successfully recorded and matched
      among this age group. The proportion of children's activity taking place in parks
      with playgrounds was low, although this may still be important for some
      subgroups.

PMID- 20153363
TI  - Structure characterization and antioxidant activity of a novel polysaccharide
      isolated from Ginkgo biloba.
AB  - A novel polysaccharide (GBP50S2) with antioxidant activity was isolated from
      Ginkgo biloba. The structure of GBP50S2 was elucidated on the basis of physico
      chemical and instrumental analyses, and its average molecular weight
      (Mw=2.30x10(5)) was determined by gel permeation chromatography. The backbone of
      GBP50S2 was composed of (1-->4)-linked alpha-d-mannopyranosyl residues which
      branched at O-3. The three branches consisted of beta-l-rhamnopyranosyl residues,
      (1-->4)-linked alpha-d-galactopyranosyl terminated with beta-l-rhamnopyranosyl
      residues, and (1-->3,4)-linked alpha-d-mannopyranosyl terminated with beta-l
      rhamnopyranosyl residues, respectively. In the in vitro antioxidant assay,
      GBP50S2 was found to possess DPPH radical-scavenging activity and hydroxyl
      radical-scavenging activity with an IC(50) value of 0.412 mg/mL and 0.482 mg/mL,
      respectively.

PMID- 20153362
TI  - Targeting anoikis resistance in prostate cancer metastasis.
AB  - Anoikis is a mode of apoptotic cell death, consequential to insufficient cell
      matrix interactions and a critical player in tumor angiogenesis and metastasis.
      The events involved in tumor cell progression toward metastasis potential are
      mediated by integrins, which upon engagement with components of the extracellular
      matrix (ECM), reorganize to form adhesion complexes. Targeting apoptotic players
      is of immense therapeutic significance since resistance to apoptosis is not only
      critical in conferring therapeutic failure to standard treatment strategies, but
      anoikis (apoptosis upon loss of anchorage and detachment from ECM) also plays an
      important role in angiogenesis and metastasis. The ability to survive in the
      absence of adhesion to the ECM, enables tumor cells to disseminate from the
      primary tumor site, invade a distant site and establish a metastatic lesion.
      Tumor cells can escape from detachment-induced apoptosis by controlling anoikis
      pathways, including the extrinsic death receptor pathway and the ECM-integrin
      mediated cell survival pathway. Considering the functional promiscuity of
      individual signaling effectors, it is critical to dissect the molecular networks
      mechanistically driving tumor cells to evade anoikis and embark on a metastatic
      spread. Resistance to die via anoikis dictates tumor cell survival and provides a
      molecular basis for therapeutic targeting of metastatic prostate cancer. Further
      dissection of critical anoikis signaling events will enable the therapeutic
      optimization of anoikis targeting to impair prostate cancer metastasis prior to
      its initiation. This review will discuss the molecular understanding of anoikis
      regulation in the tumor microenvironment and the in vivo pharmacological
      implementation of a novel class of antitumor-drugs to optimize apoptotic-based
      therapeutic targeting, bypassing anoikis-resistance to impair prostate cancer
      progression to metastasis. Potential combination strategies targeting tumor
      vascularity (via anoikis) and impairing tumor initiation (via "classic"
      apoptosis), provide strong therapeutic promise for metastatic prostate cancer by
      preventing the onset of metastasis.

PMID- 20153365
TI  - Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce
      cardiovascular risk.
AB  - Although statin therapy represents a cornerstone of cardiovascular disease (CVD)
      prevention, a major residual CVD risk (60-70% of total relative risk) remains,
      attributable to both modifiable and non-modifiable risk factors. Among the
      former, low levels of HDL-C together with elevated triglyceride (TG)-rich
      lipoproteins and their remnants represent major therapeutic targets. The current
      pandemic of obesity, metabolic syndrome, and type 2 diabetes is intimately
      associated with an atherogenic dyslipidemic phenotype featuring low HDL-C
      combined with elevated TG-rich lipoproteins and small dense LDL. In this context,
      there is renewed interest in pharmacotherapeutic strategies involving niacin and
      fibrates in monotherapy and in association with statins. This comprehensive,
      critical review of available data in dyslipidemic subjects indicates that niacin
      is more efficacious in raising HDL-C than fibrates, whereas niacin and fibrates
      reduce TG-rich lipoproteins and LDL comparably. Niacin is distinguished by its
      unique capacity to effectively lower Lp(a) levels. Several studies have
      demonstrated anti-atherosclerotic action for both niacin and fibrates. In
      contrast with statin therapy, the clinical benefit of fibrates appears limited to
      reduction of nonfatal myocardial infarction, whereas niacin (frequently
      associated with statins and/or other agents) exerts benefit across a wider range
      of cardiovascular endpoints in studies involving limited patient numbers. Clearly
      the future treatment of atherogenic dyslipidemias involving the lipid triad, as
      exemplified by the occurrence of the mixed dyslipidemic phenotype in metabolic
      syndrome, type 2 diabetes, renal, and auto-immune diseases, requires integrated
      pharmacotherapy targeted not only to proatherogenic particles, notably VLDL, IDL,
      LDL, and Lp(a), but also to atheroprotective HDL.

PMID- 20153364
TI  - Critical brain circuits at the intersection between stress and learning.
AB  - The effects of stressful life experience on learning are pervasive and vary
      greatly both within and between individuals. It is therefore unlikely that any
      one mechanism will underlie these complicated processes. Nonetheless, without
      identifying the necessary and sufficient circuitry, no complete mechanism or set
      of mechanisms can be identified. In this review, we provide two anatomical
      frameworks through which stressful life experience can influence processes
      related to learning and memory. In the first, stressful experience releases
      stress hormones, primarily from the adrenals, which directly impact brain areas
      engaged in learning. In the second, stressful experience indirectly alters the
      circuits used in learning via intermediary brain regions. Importantly, these
      intermediary brain regions are not integral to the stress response or learning
      itself, but rather link the consequences of a stressful experience with circuits
      used to learn associations. As reviewed, the existing literature provides support
      for both frameworks, with somewhat more support for the first but sufficient
      evidence for the latter which involves intermediary structures. Once we determine
      the circumstances that engage each framework and identify which one is most
      predominant, we can begin to focus our efforts on describing the neuronal and
      hormonal mechanisms that operate within these circuits to influence cognitive
      processes after stressful life experience.

PMID- 20153366
TI  - Personalized immunosuppressive therapy in pediatric heart transplantation:
      Progress, pitfalls and promises.
AB  - The use of the immunosuppressants has revolutionized organ transplantation,
      including pediatric heart transplantation (PHTx). Recent evidence has shown that
      pharmacogenomics holds the promise to maximize the likelihood of drug safety and
      efficacy after the drug and dose are tailored individually based on the
      translation of pharmacogenomics to patient care. In this review, the
      immunosuppressants used for the PHTx are introduced, including their similarities
      and differences in immunosuppressive mechanisms of action, and their unique
      clinical efficacy and safety issues in relation to genetic polymorphisms in the
      genes that encode drug-metabolizing enzymes, drug transporters and drug targets.
      In addition, genetic susceptibility to severe drug-associated complications and
      strategies for their prevention and treatment are discussed. Moreover, clinically
      important drug-drug, drug-herb, or drug-food interactions and the effects of
      demographic and clinical covariates of recipients and donors on clinical
      endpoints of the PHTx are summarized, respectively. All relevant data are focused
      mainly on the PHTx. Information provided in this review would be useful for
      pediatric patient care, in particular for personalized medication, because each
      and every valuable piece could be fitted to the big picture of how organ
      rejection would be delayed and even avoided after personalized immunosuppressive
      therapy.

PMID- 20153368
TI  - Dietary flavonoids in cancer therapy and prevention: substrates and inhibitors of
      cytochrome P450 CYP1 enzymes.
AB  - Flavonoids are polyphenolic compounds that have attracted the attention of the
      scientific community as the hallmark molecules responsible for cancer prevention
      by a plethora of different mechanisms. One of their most important
      characteristics, responsible for their cancer preventive properties, is their
      interaction with cytochrome P450 CYP1 enzymes. Flavonoids have traditionally been
      described as CYP1 inhibitors due to the inhibition of carcinogenic product
      formation and consequent blockage of the initiation stage of carcinogenesis.
      However, mounting evidence indicate that flavonoids are also capable of acting as
      CYP1 substrates, undergoing bioactivation to more antiproliferative agents within
      cancer cells. In this review, a comprehensive summary of the two models is
      presented. Structural features responsible for CYP1 inhibition or substrate
      turnover are discussed and limitations as well as discrepancies between
      procarcinogen-activating and 7-ethoxyresorufin-inhibition assay systems are
      further explored in vitro and in vivo. Moreover, a thorough investigation of the
      substrate specificity of flavonoids for the active site of CYP1 enzymes is
      undertaken. Finally, issues concerning the bioavailability and metabolic fate of
      these compounds in vivo are addressed. Ultimately, the mode of flavonoid action,
      in terms of CYP1 inhibition or CYP1-mediated bioactivation, is dependent on the
      lipophilicity or hydrophilicity of each compound. The degree of hydroxylation or
      methoxylation of the A and B rings is the major factor which determines the
      accessibility to the tumor site, in terms of hepatic and intestinal metabolism,
      and the introduction of the molecules to the CYP1 active site, respectively.

PMID- 20153369
TI  - Microsurgical approach to the spinal canal in rats.
AB  - The spinal cord of the rat has become a widely used model for biodynamic,
      pharmaceutical and neurological experiments. However, no standard procedure to
      approach the spinal cord in rats has been published in detail. We present a
      description of a dorsal approach to the spine, spinal canal and myelon of the
      rat. This approach provides sufficient exposure of the neural structures to
      perform extended microsurgery at the spinal nerve-roots, the lateral and dorsal
      myelon and vertebral structures under a surgical microscope. Perioperative
      management, anaesthesia and anatomical landmarks are discussed and common
      pitfalls are described.

PMID- 20153370
TI  - A bio-friendly and economical technique for chronic implantation of multiple
      microelectrode arrays.
AB  - Many neurophysiological experiments on rodents and non-human primates involve the
      implantation of more than one multi-electrode array to record from many regions
      of the brain. So called 'floating' microelectrode arrays are implanted in
      cortical regions of interest and are coupled via a flexible cable to their
      connectors which are fixed to the skull by a cement cap or a titanium pedestal,
      such as the Cereport system, which has been approved for human use. The use of
      bone cement has several disadvantages including the creation of infection prone
      areas at the interface with the skull and surrounding skin. Alternatively, the
      more biocompatible Cereport has a limited carrying capacity and is far more
      expensive. In this paper, we describe a new implantation technique, which
      combines the biocompatibility of titanium, a high carrying capacity with a
      minimal skull footprint, and a decreased chance of infection, all in a relatively
      inexpensive package. This technique utilizes an in-house fabricated 'Nesting
      Platform' (NP), mounted on a titanium headpost to hold multiple connectors above
      the skin, making the headpost the only transcutaneous object. The use of delrin,
      a durable, lightweight and easily machinable material, allows easy customization
      of the NP for a wide variety of floating electrodes and their connectors. The
      ultimate result is a longer survival time with superior neural recordings that
      can potentially last longer than with traditional implantation techniques.

PMID- 20153371
TI  - Improved signal processing approaches in an offline simulation of a hybrid brain
      computer interface.
AB  - In a conventional brain-computer interface (BCI) system, users perform mental
      tasks that yield specific patterns of brain activity. A pattern recognition
      system determines which brain activity pattern a user is producing and thereby
      infers the user's mental task, allowing users to send messages or commands
      through brain activity alone. Unfortunately, despite extensive research to
      improve classification accuracy, BCIs almost always exhibit errors, which are
      sometimes so severe that effective communication is impossible. We recently
      introduced a new idea to improve accuracy, especially for users with poor
      performance. In an offline simulation of a "hybrid" BCI, subjects performed two
      mental tasks independently and then simultaneously. This hybrid BCI could use two
      different types of brain signals common in BCIs - event-related desynchronization
      (ERD) and steady-state evoked potentials (SSEPs). This study suggested that such
      a hybrid BCI is feasible. Here, we re-analyzed the data from our initial study.
      We explored eight different signal processing methods that aimed to improve
      classification and further assess both the causes and the extent of the benefits
      of the hybrid condition. Most analyses showed that the improved methods described
      here yielded a statistically significant improvement over our initial study. Some
      of these improvements could be relevant to conventional BCIs as well. Moreover,
      the number of illiterates could be reduced with the hybrid condition. Results are
      also discussed in terms of dual task interference and relevance to protocol
      design in hybrid BCIs.

PMID- 20153372
TI  - An organotypic culture model to study nigro-striatal degeneration.
AB  - Functional and reliable in vitro models of Parkinson's disease (PD) are valuable
      for studying mechanisms of dopaminergic degeneration before proceeding to animal
      testing. At present, all in vitro models involve substitute cell types and thus
      their direct relevance to PD is questionable. Here, we describe an organotypic
      culture model which conserves the 3D architecture of the nigro-striatal pathway,
      together with the subventricular zone and cerebral cortex, and recapitulates a
      specific pattern of dopaminergic degeneration which is the principal hallmark of
      PD. The organotypic culture is kept in vitro for up to 12 days and dopaminergic
      degeneration is induced by the simple cutting of dopaminergic fibers. This
      organotypic model represents a rapid and useful method (30 min/pup for
      preparation and up to 12 days of cultivation) to investigate in vitro the
      mechanisms underlying neuronal death and protection, as well as neurogenesis and
      repair after nigro-striatal neurodegeneration.

PMID- 20153374
TI  - Characterization of lentiviral pseudotypes with influenza H5N1 hemagglutinin and
      their performance in neutralization assays.
AB  - Pseudotype reporter viruses are being used as safe, quantitative, and high
      throughput tools for assessing antibody neutralization for many viruses,
      including influenza. However, characterization of pseudotypes containing
      influenza hemagglutinin (HA-pseudotypes) is needed before this system is widely
      adopted for evaluating neutralizing antibodies in sera following vaccination or
      infection. In this report HA-pseudotype stocks were analyzed for HA content,
      stability, and performance in neutralization assays under various conditions. HA
      pseudotypes produced with HA genes of H5 strains representing clades 1, 2.2, and
      2.3.4 consistently contain similar HA contents, and infectivity was not greatly
      affected by the purity of the HA-pseudotype preparations or variations in storage
      conditions. HA-pseudotype neutralization titers using a reference serum panel
      were also consistent across a wide range of dilutions of HA-pseudotype stocks and
      correlated well with results from microneutralization assays involving
      replicating influenza. Concentrated HA-pseudotypes were further shown to work
      well in hemagglutination inhibition assays. Finally, antisera elicited by
      genetically modified HA, with changes in the polybasic cleavage site that have
      been used in some H5 vaccines and reduce pathogenicity, gave identical
      neutralization titers against HA-pseudotypes with wild type or modified HA. These
      findings support continued development of HA-pseudotypes as a robust tool for
      analyzing sera in vaccine and serologic studies.

PMID- 20153373
TI  - Development of a high-content screening assay to identify compounds interfering
      with the formation of the hepatitis C virus replication complex.
AB  - The hepatitis C virus (HCV) replicates its genome on a membrane-associated
      replication complex. These complexes are represented by "dot-like" structures on
      the endoplasmic reticulum when standard fluorescence microscopy techniques are
      applied. To screen compound libraries for inhibitors interfering with the
      formation of the HCV replication complex independent of RNA replication, an image
      based high-content screening assay was developed utilizing inducible expression
      of the HCV non-structural proteins NS3-5B in an U2-OS Tet-On cell line. An eGFP
      was fused to NS5A for the detection of replication complexes. The cell line was
      tightly regulated and the eGFP insertion within NS5A did not alter polyprotein
      processing. The NS5AeGFP signal colocalized with other non-structural proteins in
      "dot-like" structures. Accompanying image analysis tools were developed enabling
      the detection of changes in replication complex formation. Finally, the addition
      of a HCV NS3/4A protease inhibitor resulted in a dose-dependent reduction of "dot
      like" structures demonstrating the practicability of the assay.

PMID- 20153375
TI  - Assessment of the susceptibility of mutant HIV-1 to antiviral agents.
AB  - Traditional phenotypic assays used to assess the susceptibility of mutant human
      immunodeficiency virus type-1 (HIV-1) obtained from infected patients or from
      resistance selection to antiviral agents in cell culture are rather tedious and
      time consuming. To improve the efficiency of this process, a novel method was
      developed in which mutant viruses are captured with magnetic nano-beads and used
      to infect gag-GFP reporter cells to evaluate the extent of resistance conferred
      by the mutant viruses against antiviral agents. The optimal timing for measuring
      the inhibitory potencies of antiviral agents was found to be day 3 post-infection
      for integrase strand transfer inhibitors and protease inhibitors and day 4 for
      non-nucleoside reverse transcriptase inhibitors. Comparable EC(50) values were
      obtained when bead-captured breakthrough virus from in vitro resistance selection
      experiments and its matched site-directed mutagenesis virus were tested side by
      side in this assay. This assay protocol was also employed to evaluate the
      inhibitor susceptibility of breakthrough viruses collected from resistance
      selections that were conducted in the presence of increasing concentrations of an
      HIV-1 protease inhibitor. Taken together, these findings suggest that a rapid,
      sensitive, non-invasive, and homogeneous phenotypic assay has been developed for
      assessing the antiviral agent susceptibility of mutant viruses that emerge from
      in vitro resistance selection studies.

PMID- 20153376
TI  - Differentiation of Tomato yellow leaf curl virus and Tomato yellow leaf curl
      Sardinia virus using real-time TaqMan PCR.
AB  - During the past four decades, Tomato yellow leaf curl disease has become one of
      the major constraints in tomato production worldwide. In the Mediterranean basin,
      several isolates from two major Begomovirus species are involved in outbreaks and
      persistent epidemics. A real-time TaqMan PCR assay was developed and evaluated
      for the rapid and multiplex detection and differentiation of two begomoviruses
      often found in mixed infections in the region, Tomato yellow leaf curl virus
      (TYLCV) and Tomato yellow leaf curl Sardinia virus (TYLCSV). This assay was 1000
      fold more sensitive than conventional PCR assays described previously, allowing
      the use of simple template preparation methods and eliminating the need for total
      nucleic acid purification. The viral DNA template was obtained by spotting sap
      extract derived from TYLCV or TYLCSV infected tissues on a nylon membrane or by
      directly using crude plant extracts in the real-time reaction cocktail.
      Preliminary results showed that this method can successfully detect and
      discriminate virus species from infected tomato, bean, pepper and different weed
      species obtained from the Mediterranean basin, the USA and Japan, allowing the
      simple, fast and cost-effective testing of a large number of samples in
      certification schemes. The assay can also be used for the detection of these two
      begomovirus species in their whitefly vector biotypes of the Bemisia tabaci
      (Gennadius) species group.

PMID- 20153377
TI  - A novel multiplex real-time RT-PCR assay with FRET hybridization probes for the
      detection and quantitation of 13 respiratory viruses.
AB  - Quantitative multiplex real-time RT-PCR assays utilizing fluorescence resonance
      energy transfer (FRET) hybridization probes were developed for the detection of
      13 respiratory viruses, including well recognized viral causes (respiratory
      syncytial virus, influenza viruses A and B, parainfluenza viruses types 1, 2, and
      3, adenovirus) as well as viruses described recently as causes of acute
      respiratory tract infections (human coronaviruses NL63, HKU1, 229E, and OC43,
      human bocavirus, and human metapneumovirus). FRET probes have an improved
      toleration for single base mismatches than other probe chemistries, reducing the
      chances of missing highly variable RNA viruses. The assay could detect 2.5-25
      DNA/RNA copies/microl (2.5 x 10(3)-2.5 x 10(4) copies/ml). Validation on 91 known
      positive respiratory specimens indicated similar specificity as commercial direct
      immunofluorescence assays (IFA) or single-round PCRs used in initial
      identification. Screening of 270 IFA negative respiratory specimens identified
      new viruses in 40/270 (14.8%) cases and additional 79/270 (29.3%) well recognized
      viruses missed by routine diagnostic assays including 6.7% co-infections. All
      viruses could be detected in the clinical screening panel. The assays
      demonstrates an improved sensitivity and scope of detecting respiratory viruses
      relative to routine antigen detection assays while the quantitative utility may
      facilitate investigation of the role of co-infections and viral load in
      respiratory virus pathogenesis.

PMID- 20153367
TI  - Effects of tempol and redox-cycling nitroxides in models of oxidative stress.
AB  - Tempol is a redox-cycling nitroxide that promotes the metabolism of many reactive
      oxygen species (ROS) and improves nitric oxide bioavailability. It has been
      studied extensively in animal models of oxidative stress. Tempol has been shown
      to preserve mitochondria against oxidative damage and improve tissue oxygenation.
      Tempol improved insulin responsiveness in models of diabetes mellitus and
      improved the dyslipidemia, reduced the weight gain and prevented diastolic
      dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol
      protected many organs, including the heart and brain, from ischemia/reperfusion
      damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and
      progressive loss of renal function in models of salt and mineralocorticosteroid
      excess. It reduced brain or spinal cord damage after ischemia or trauma and
      exerted a spinal analgesic action. Tempol improved survival in several models of
      shock. It protected normal cells from radiation while maintaining radiation
      sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells
      accounted for a reduction in spontaneous tumor formation. Tempol was effective in
      some models of neurodegeneration. Thus, tempol has been effective in preventing
      several of the adverse consequences of oxidative stress and inflammation that
      underlie radiation damage and many of the diseases associated with aging. Indeed,
      tempol given from birth prolonged the life span of normal mice. However,
      presently tempol has been used only in human subjects as a topical agent to
      prevent radiation-induced alopecia.

PMID- 20153378
TI  - Effect of ritonavir and atazanavir on human subcutaneous preadipocyte
      proliferation and differentiation.
AB  - Protease inhibitors (PIs) have been implicated in the development of HIV
      associated lipodystrophy through a reduction in the differentiation of
      preadipocytes. While atazanavir (ATV) is associated with fewer clinical metabolic
      abnormalities in the short-term, the effects of long-term exposure are not known.
      ATV effects on preadipocyte replication or differentiation would indicate the
      potential for long-term problems. This study compared ritonavir (RTV) and ATV
      effects on preadipocyte replication and differentiation in human primary
      cultures. Preadipocytes from subcutaneous fat were studied in the presence of
      therapeutic concentrations of RTV and ATV for replication, differentiation, and
      adipokine secretion. The effects of the drugs on the expression of PPARgamma and
      related genes during differentiation were also assessed by real-time quantitative
      PCR. RTV induced a significant inhibition of preadipocyte proliferation,
      differentiation and adiponectin secretion. ATV at concentrations within the range
      of therapeutic levels did not affect differentiation or adiponectin secretion,
      but did have inhibitory effects on preadipocyte proliferation. Inhibition of
      differentiation by PIs was associated with decreased expression of PPARgamma,
      C/EBPalpha, and aP2 genes. In summary, although ATV at therapeutic levels has a
      smaller impact on adipogenesis, alterations in preadipocyte proliferation suggest
      the potential for adverse effects with long-term use.

PMID- 20153379
TI  - Practical application of bioinformatics by the multidisciplinary VIZIER
      consortium.
AB  - This review focuses on bioinformatics technologies employed by the EU-sponsored
      multidisciplinary VIZIER consortium (Comparative Structural Genomics of Viral
      Enzymes Involved in Replication, FP6 PROJECT: 2004-511960, active from 1 November
      2004 to 30 April 2009), to achieve its goals. From the management of the
      information flow of the project, to bioinformatics-mediated selection of RNA
      viruses and prediction of protein targets, to the analysis of 3D protein
      structures and antiviral compounds, these technologies provided a communication
      framework and integrated solutions for steady and timely advancement of the
      project. RNA viruses form a large class of major pathogens that affect humans and
      domestic animals. Such RNA viruses as HIV, Influenza virus and Hepatitis C virus
      are of prime medical concern today, but the identities of viruses that will
      threaten human population tomorrow are far from certain. To contain outbreaks of
      common or newly emerging infections, prototype drugs against viruses representing
      the Virus Universe must be developed. This concept was championed by the VIZIER
      project which brought together experts in diverse fields to produce a concerted
      and sustained effort for identifying and validating targets for antivirus therapy
      in dozens of RNA virus lineages.

PMID- 20153380
TI  - Effects of reversible inactivation of the medial septum on rat exploratory
      behavior in the elevated plus-maze using a test-retest paradigm.
AB  - The effect of intraseptal injections of lidocaine before a first or a second
      session in the elevated plus-maze, in a test-retest paradigm, was investigated.
      In addition to gross session analyses, a minute-by-minute analysis of the
      sessions was used to evaluate both anxiety and memory. Lidocaine injections
      before the test session produced increases in the frequency of entries, time
      spent and distance run in the open arms without affecting activity occurring in
      the closed arms. During the retest session, saline- and lidocaine-treated rats
      exhibited increased indices of anxiety and lidocaine-treated rats exhibited
      decreased closed-arm entries. The minute-by-minute analysis showed a faster
      decrease in anxiety-related behaviors during the test session by saline- than by
      lidocaine-treated rats and a significant decrease in closed-arm exploration by
      saline-treated rats, but not by lidocaine-treated ones. Lidocaine injection
      before the retest session produced increases in the frequency of entries, time
      spent and distance run in the open arms in the second session when compared with
      saline-treated rats. Minute-by-minute analysis showed an increase in the time
      spent in the open arms by lidocaine animals at the beginning of the retest
      session in comparison to saline animals and a significant decrease in closed-arm
      exploration by both groups. These results suggest that inactivation of the medial
      septum by lidocaine affects the expression of unconditioned and conditioned forms
      of anxiety in the elevated plus-maze and, in a lesser way, the acquisition and
      retention of spatial information.

PMID- 20153381
TI  - Enhanced habit-based learning and decreased neurogenesis in the adult hippocampus
      in a murine model of chronic social stress.
AB  - Stress can induce preferential engagement of habit learning mediated by the basal
      ganglia, relative to learning that involves complex spatial associations
      contributed by the hippocampal formation. We explored in mice the influence that
      chronic episodes of social stress exert on the selection of cognitive/spatial vs.
      habit-based learning strategies. Male mice were exposed to repeated episodes of
      social confrontation and were categorized as dominant, subordinate or
      undetermined according to quantitative ethologically relevant parameters of
      aggression. Mice were then trained in a conditional discrimination task in the T
      maze in the presence of allocentric cues until five correct choices were made.
      The T-maze was then turned 180 degrees and mice were categorized as "cue
      learners" or "place-learners" on the basis of their first response in the probe
      test. Mice showed a graded preference for place vs. cue learning strategies
      depending on their social categorization
      (control>undetermined>dominant>subordinate), which ranged from 55% in controls to
      only 10% in subordinate mice. The response of subordinate mice differed
      significantly from controls. Hippocampal neurogenesis was studied in the
      different groups of mice. In keeping with the tendency to engage habit learning,
      2,5-bromodeoxyuridine (BrdU) incorporation in the DG was reduced in mice that
      experienced agonistic encounters, and so was the expression of doublecortin, a
      marker for immature neurons. These observations suggest that chronic social
      stress impairs neurogenesis in the adult hippocampus, weakens spatial learning
      and strengthens habit-like responses.

PMID- 20153382
TI  - Development of a Real-Time PCR assay for quantitative assessment of uncultured
      freshwater zoosporic fungi.
AB  - Recently, molecular environmental surveys of the eukaryotic microbial community
      in lakes have revealed a high diversity of sequences belonging to uncultured
      zoosporic fungi. Although they are known as saprobes and algal parasites in
      freshwater systems, zoosporic fungi have been neglected in microbial food web
      studies. Recently, it has been suggested that zoosporic fungi, via the
      consumption of their zoospores by zooplankters, could transfer energy from large
      inedible algae and particulate organic material to higher trophic levels.
      However, because of their small size and their lack of distinctive morphological
      features, traditional microscopy does not allow the detection of fungal zoospores
      in the field. Hence, quantitative data on fungal zoospores in natural
      environments is missing. We have developed a quantitative PCR (qPCR) assay for
      the quantification of fungal zoospores in lakes. Specific primers were designed
      and qPCR conditions were optimized using a range of target and non-target
      plasmids obtained from previous freshwater environmental 18S rDNA surveys. When
      optimal DNA extraction protocol and qPCR conditions were applied, the qPCR assay
      developed in this study demonstrated high specificity and sensitivity, with as
      low as 100 18S rDNA copies per reaction detected. Although the present work
      focuses on the design and optimization of a new qPCR assay, its application to
      natural samples indicated that qPCR offers a promising tool for quantitative
      assessment of fungal zoospores in natural environments. We conclude that this
      will contribute to a better understanding of the ecological significance of
      zoosporic fungi in microbial food webs of pelagic ecosystems.

PMID- 20153383
TI  - Quantification of Pseudomonas fluorescens strains F113, CHA0 and Pf153 in the
      rhizosphere of maize by strain-specific real-time PCR unaffected by the
      variability of DNA extraction efficiency.
AB  - Pseudomonas fluorescens strains F113 and CHA0 are well-known plant growth
      promoting rhizobacteria (PGPR) often used as model strains in biocontrol
      experiments. To monitor their persistence in large scale field experiments,
      culture-independent methods are needed. In this study, a strain-specific real
      time PCR quantification tool was developed based on sequence-characterized
      amplified regions (SCAR) for P. fluorescens strains F113, CHA0 and Pf153.
      Differences in DNA extraction efficiencies from rhizosphere samples were
      circumvented using plasmid APA9 as internal standard to normalize C(T) values
      after real-time amplification. The detection limits of the real-time PCR assays
      for all three strains were approximately 10 cells for genomic DNA and
      10(4)cells/g rhizosphere for maize samples grown in different natural soils.
      Population sizes of the three strains in the rhizosphere of maize measured by the
      new real-time PCR approaches were similar to those measured by most probable
      number (MPN)-PCR. A persistence study of the three strains indicated that the
      strains persisted differently over a period of 5weeks. In conclusion the newly
      developed real-time PCR approach is a fast and resource efficient method for
      monitoring individual biocontrol strains in natural soil, which makes it an apt
      quantification tool for future large-scale field experiments.

PMID- 20153384
TI  - Behavioral analyses of transgenic mice harboring bipolar disorder candidate
      genes, IMPA1 and IMPA2.
AB  - The inositol depletion hypothesis proposes the inhibition of IMPase (myo-inositol
      monophosphatase) by lithium, a mood stabilizer, as a mechanism of lithium's
      efficacy. This hypothesis predicts that the upregulation of this biochemical
      pathway may underlie the pathophysiology of bipolar disorder. In favor of this
      idea, IMPA2 encoding IMPase is a candidate susceptibility gene for bipolar
      disorder and that the risk-conferring single nucleotide polymorphisms enhance the
      promoter activity of IMPA2. However, it is yet unknown whether such upregulation
      has a biological role in bipolar disorder. To address this issue, we generated
      transgenic mice for the two IMPase genes (IMPA1 and IMPA2). The expression levels
      of the transgene were robust in IMPA2 Tg lines, but moderate in IMPA1 Tg lines,
      when compared to those of endogenous proteins. The transgenic mice behaved
      normally under drug-naive conditions, and did not exhibit signs for manic change
      when an antidepressant amitriptyline was administrated. Interestingly, the male
      transgenic mice for IMPA2 exhibited a lithium-resistant phenotype in the forced
      swim test. The current study, as a whole, did not support a substantial role of
      the upregulation of IMPase in bipolar disorder, although the lithium
      insensitivity trait seen in IMPA2 transgenic mice might represent some aspect
      relevant to the inositol depletion hypothesis.

PMID- 20153385
TI  - Formulation, characterization and pulmonary deposition of nebulized celecoxib
      encapsulated nanostructured lipid carriers.
AB  - The aim of the current study was to encapsulate celecoxib (Cxb) in the
      nanostructured lipid carrier (Cxb-NLC) nanoparticles and evaluate the lung
      disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC
      nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate
      using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for
      physical and aerosol properties. In-vitro cytotoxicity studies were performed
      with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC
      and Cxb solution (Cxb-Soln) formulations were determined using the Inexpose
      system and Pari LC star jet nebulizer. The particle size and entrapment
      efficiency of the Cxb-NLC formulation were 217+/-20nm and >90%, respectively. The
      Cxb-NLC released the drug in controlled fashion, and in-vitro aerosolization of
      Cxb-NLC formulation showed an FPF of 75.6+/-4.6%, MMAD of 1.6+/-0.13microm and a
      GSD of 1.2+/-0.21. Cxb-NLC showed dose and time dependent cytotoxicity against
      A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUC(t)/D in lung
      tissues compared to the Cxb-Soln. The systemic clearance of Cxb-NLC was slower
      (0.93l/h) compared to the Cxb-Soln (20.03l/h). Cxb encapsulated NLC were found to
      be stable and aerodynamic properties were within the respirable limits.
      Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to
      solution formulation which will potentially lead to better patient compliance
      with minimal dosing intervals.

PMID- 20153387
TI  - Scaffold-free cell delivery for use in regenerative medicine.
AB  - The development of cell-based therapies for diseased tissues is one of the most
      promising research directions in regenerative medicine. Cell-delivery methods are
      an essential part of cell therapy concepts. Therapies with the potential to
      become clinical routine will only be possible if these methods ensure efficient
      engraftment and therapeutically-relevant number of cells survive. Here we provide
      an overview of three different scaffold-free cell-delivery concepts: (i) single
      cell delivery, (ii) cell sheet engineering and (iii) microtissue technology.

PMID- 20153386
TI  - Fibrin-mediated lentivirus gene transfer: implications for lentivirus
      microarrays.
AB  - We employed fibrin hydrogel as a bioactive matrix for lentivirus mediated gene
      transfer. Fibrin-mediated gene transfer was highly efficient and exhibited strong
      dependence on fibrinogen concentration. Efficient gene transfer was achieved with
      fibrinogen concentration between 3.75 and 7.5mg/ml. Lower fibrinogen
      concentrations resulted in diffusion of virus out of the gel while higher
      concentrations led to ineffective fibrin degradation by target cells. Addition of
      fibrinolytic inhibitors decreased gene transfer in a dose-dependent manner
      suggesting that fibrin degradation by target cells may be necessary for
      successful gene delivery. Under these conditions transduction may be limited only
      to cells interacting with the matrix thereby providing a method for spatially
      localized gene delivery. Indeed, when lentivirus-containing fibrin microgels were
      spotted in an array format gene transfer was confined to virus-containing fibrin
      spots with minimal cross-contamination between neighboring sites. Collectively,
      our data suggest that fibrin may provide an effective matrix for spatially
      localized gene delivery with potential applications in high-throughput lentiviral
      microarrays and in regenerative medicine.

PMID- 20153388
TI  - Microcapsules and microcarriers for in situ cell delivery.
AB  - In recent years, the use of transplanted living cells pumping out active factors
      directly at the site has proven to be an emergent technology. However a recurring
      impediment to rapid development in the field is the immune rejection of
      transplanted allo- or xenogeneic cells. Immunosuppression is used clinically to
      prevent rejection of organ and cell transplants in humans, but prolonged usage
      can make the recipient vulnerable to infections, and increase the likelihood of
      tumorigenesis of the transplanted cells. Cell microencapsulation is a promising
      tool to overcome these drawbacks. It consists of surrounding cells with a
      semipermeable polymeric membrane. The latter permits the entry of nutrients and
      the exit of therapeutic protein products, obtaining in this way a sustained
      delivery of the desirable molecule. The membrane isolates the enclosed cells from
      the host immune system, preventing the recognition of the immobilization cells as
      foreign. This review paper intends to overview the current situation in the cell
      encapsulation field and discusses the main events that have occurred along the
      way. The technical advances together with the ever increasing knowledge and
      experience in the field will undoubtedly lead to the realization of the full
      potential of cell encapsulation in the future.

PMID- 20153389
TI  - Feeding patterns and behaviors during home supplementation of underweight
      Malawian children with lipid-based nutrient supplements or corn-soy blend.
AB  - The way caregivers use supplementary food for undernourished children and
      integrate it into feeding patterns may influence the benefits achieved by
      supplementation. We studied feeding patterns and behaviors in 170 underweight 6
      17-month-olds who received either lipid-based nutrient supplements (LNS) (n=85)
      or corn-soy blend (CSB) (n=85) during a 12-week intervention trial in southern
      Malawi. Observational data were collected during one 11h home visit per
      participant. Differences were assessed by study group and by mode of serving LNS.
      Associations between selected caregiver behaviors and child growth were also
      tested. We found no difference between the CSB and LNS groups in mean number of
      feeding episodes per day or mean daily feeding time. Caregivers fed the child
      with a spoon, washed their hands before feeding, and there were leftovers
      significantly more often in the CSB than LNS group and when LNS mixed with
      porridge and plain LNS were compared. This suggests that differences between the
      groups were linked to the mode of serving LNS. Presence of leftovers was
      negatively associated with change in child's WAZ. Programs promoting LNS in
      Malawi should consider behaviors related to mode of serving and provide advice to
      caregivers in order to minimize leftovers during supplement use.

PMID- 20153390
TI  - Protein information content resides in rare peptide segments.
AB  - Discovering the informational rule(s) underlying structure-function relationships
      in the protein language is at the core of biology. Current theories have proven
      inadequate to explain the origins of biological information such as that found in
      nucleotide and amino acid sequences. Here, we demonstrate that the information
      content of an amino acid motif correlates with the motif rarity. A structured
      analysis of the scientific literature supports the theory that rare pentapeptide
      words have higher significance than more common pentapeptides in biological cell
      'talk'. This study expands on our previous research showing that the
      immunological information contained in an amino acid sequence is inversely
      related to the sequence frequency in the host proteome.

PMID- 20153391
TI  - Stimulation of N-cadherin-dependent neurite outgrowth by small molecule peptide
      mimetic agonists of the N-cadherin HAV motif.
AB  - N-cadherin is a cell adhesion molecule that promotes axon outgrowth and synapse
      formation during the development of the central nervous system. In addition, N
      cadherin promotes glial cell adhesion and myelination of axons. Therefore,
      stimulating N-cadherin function with N-cadherin agonists could be used
      therapeutically to promote regeneration of the nervous system and remyelination
      after injury or disease. In the extracellular domain of N-cadherin, the amino
      acid sequence HAV is required for N-cadherin-mediated adhesion and neurite
      outgrowth. The ADH-1 cyclic peptide, derived from the N-cadherin HAV site, is an
      effective antagonist of N-cadherin-mediated neurite outgrowth and is currently
      being tested in clinical trials for cancer chemotherapy. Of interest, a dimeric
      version of this cyclic peptide, N-Ac-CHAVDINGHAVDIC-NH(2), functions as an N
      cadherin agonist. This dimeric peptide agonist and the peptide antagonist ADH-1
      both have limitations as drugs due to their metabolic instability and lack of
      oral delivery. To address this issue Adherex Technologies Inc. generated a small
      molecule library of peptidomimetics to the HAV region of N-cadherin, which would
      be more amenable to therapeutic use. We screened the Adherex library for
      compounds that altered neurite outgrowth and identified eight N-cadherin agonists
      that stimulated N-cadherin-dependent neurite outgrowth. Five of these agonists
      also stimulated retinal cell migration. These small molecule agonists may be
      effective reagents for promoting axon growth and remyelination after injury or
      disease.

PMID- 20153392
TI  - The swaposin-like domain of potato aspartic protease (StAsp-PSI) exerts
      antimicrobial activity on plant and human pathogens.
AB  - Plant-specific insert domain (PSI) is a region of approximately 100 amino acid
      residues present in most plant aspartic protease (AP) precursors. PSI is not a
      true saposin domain; it is the exchange of the N- and C-terminal portions of the
      saposin like domain. Hence, PSI is called a swaposin domain. Here, we report the
      cloned, heterologous expression and purification of PSI from StAsp 1 (Solanum
      tuberosum aspartic protease 1), called StAsp-PSI. Results obtained here show that
      StAsp-PSI is able to kill spores of two potato pathogens in a dose-dependent
      manner without any deleterious effect on plant cells. As reported for StAPs (S.
      tuberosum aspartic proteases), the StAsp-PSI ability to kill microbial pathogens
      is dependent on the direct interaction of the protein with the microbial cell
      wall/or membrane, leading to increased permeability and lysis. Additionally, we
      demonstrated that, like proteins of the SAPLIP family, StAsp-PSI and StAPs are
      cytotoxic to Gram-negative and Gram-positive bacteria in a dose dependent manner.
      The amino acid residues conserved in SP_B (pulmonary surfactant protein B) and
      StAsp-PSI could explain the cytotoxic activity exerted by StAsp-PSI and StAPs
      against Gram-positive bacteria. These results and data previously reported
      suggest that the presence of the PSI domain in mature StAPs could be related to
      their antimicrobial activity.

PMID- 20153393
TI  - Chemical identification of nestin-immunoreactive neurons in the rat basal
      forebrain: a re-examination.
AB  - This study explores recently identified neurons that express the protein nestin
      in the medial septum-diagonal band of Broca (MS-DBB) of adult rats and humans.
      These nestin positive neurons from MS-DBB are known to project to the hippocampus
      and frontal cortex of the brain. However, their chemical identification has not
      been fully elucidated. In this study, we further investigated the chemical
      identity of the nestin-immunoreactive (ir) neurons in rats using double
      immunofluorescence labeling and single cell reverse transcription polymerase
      chain reaction (RT-PCR) techniques. The results of double labeling showed that
      all nestin-ir neurons exhibited choline acetyltransferase (ChAT) immunoreactivity
      in the MS-DBB of the basal forebrain. Conversely, only about 43% of the ChAT-ir
      neurons showed nestin immunoreactivity. In addition, a vast majority of the
      nestin-ir neurons (95%) were nerve growth factor receptor (NGFR) positive. The
      nestin-ir neurons were highly distributed in the rostral and intermediated
      regions of the MS-DBB. Single cell RT-PCR results showed that 90% of the nestin
      mRNA expressed neurons displayed ChAT mRNA expression as well, but neither the
      mRNA of the proteins glutamic acid decarboxylases 67 (GAD67) nor vesicular
      glutamate transporters (VGLUTs). These results provide the first evidence that
      nestin-ir neurons in the basal forebrain are a subpopulation of the classic
      cholinergic neurons. With high NGFR proteins activated in the nestin-ir neurons,
      we propose that the presence of nestin in the cholinergic neurons might be
      related to the survival and plasticity of the cholinergic neurons.

PMID- 20153394
TI  - n-3 long-chain fatty acids and regulation of glucose transport in two models of
      rat brain endothelial cells.
AB  - Several in vivo studies suggest that docosahexaenoic acid (22:6 n-3), the main n
      3 long-chain polyunsaturated fatty acids (LC-PUFA) of brain membranes, could be
      an important regulator of brain energy metabolism by affecting glucose
      utilization and the density of the two isoforms of the glucose transporter-1
      (GLUT1) (endothelial and astrocytic). This study was conducted to test the
      hypothesis that 22:6 n-3 in membranes may modulate glucose metabolism in brain
      endothelial cells. It compared the impact of 22:6 n-3 and the other two main LC
      PUFA, arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3), on fatty
      acid composition of membrane phospholipids, glucose uptake and expression of 55
      kDa GLUT1 isoform in two models of rat brain endothelial cells (RBEC), in primary
      culture and in the immortalized rat brain endothelial cell line RBE4. Without
      PUFA supplementation, both types of cerebral endothelial cells were depleted in
      22:6 n-3, RBE4 being also particularly low in 20:4 n-6. After exposure to
      supplemental 20:4 n-6, 20:5 n-3 or 22:6 n-3 (15microM, i.e. a physiological
      dose), RBEC and RBE4 avidly incorporated these PUFA into their membrane
      phospholipids thereby resembling physiological conditions, i.e. the PUFA content
      of rat cerebral microvessels. However, RBE4 were unable to incorporate
      physiological level of 20:4 n-6. Basal glucose transport in RBEC (rate of [(3)H]
      3-o-methylglucose uptake) was increased after 20:5 n-3 or 22:6 n-3
      supplementation by 50% and 35%, respectively, whereas it was unchanged with 20:4
      n-6. This increase of glucose transport was associated with an increased GLUT1
      protein, while GLUT1 mRNA was not affected. The different PUFA did not impact on
      glucose uptake in RBE4. Due to alterations in n-6 PUFA metabolism and weak
      expression of GLUT1, RBE4 seems to be less adequate than RBEC to study PUFA
      metabolism and glucose transport in brain endothelial cells. Physiological doses
      of n-3 LC-PUFA have a direct and positive effect on glucose transport and GLUT1
      density in RBEC that could partly explain decreased brain glucose utilization in
      n-3 PUFA-deprived rats.

PMID- 20153395
TI  - A2BP1 as a novel susceptible gene for primary biliary cirrhosis in Japanese
      patients.
AB  - Primary biliary cirrhosis (PBC) is a complex autoimmune liver disease with an
      etiology that remains to be conclusively elucidated. As such, we screened the
      human genome for genes that might influence PBC susceptibility or resistance
      using 400 microsatellite markers. A strong candidate gene indicated by
      susceptibility microsatellite markers was further evaluated by association
      analysis using single nucleotide polymorphisms (SNPs). A total of 126 patients
      with PBC and 95 healthy Japanese controls were enrolled. Four candidate
      susceptible regions and seven candidate protective regions were statistically
      associated with PBC. Because the D16S423 marker on chromosome 16p showed the
      strongest evidence of linkage, the protein-coding gene ataxin 2-binding protein 1
      (A2BP1) lying 27 kb on the centromeric side of D16S423 was targeted as a
      candidate susceptible gene. Seven SNPs (rs17139207, rs12926282, rs17139244,
      rs6500742, rs4146812, rs4124065, and rs889699) in the A2BP1 gene were genotyped
      in patients and controls. The rs17139244 SNP was found to be weakly associated
      with PBC in an additive model. The genotype frequency of the major C allele at
      rs6500742 was significantly associated with PBC, compared with healthy controls.
      This study showed a total of 11 candidate PBC susceptibility or resistance
      regions. In particular, the A2BP1 gene might play a pivotal role for
      susceptibility to PBC.

PMID- 20153396
TI  - Prostate cancer patients on androgen deprivation therapy develop persistent
      changes in adaptive immune responses.
AB  - Prostate cancer is a significant cause of morbidity and mortality among men
      worldwide. The cornerstone treatment for metastatic prostate cancer is androgen
      deprivation, which has known effects on prostate tissue apoptosis and thymic
      regrowth. These findings, together with interest in developing immune-based
      treatments for prostate cancer, lead us to question whether androgen deprivation
      causes changes in the adaptive immune responses of prostate cancer patients, and
      whether the timing of changes has implications for the sequencing of
      immunotherapies in combination with androgen deprivation. Peripheral blood
      mononuclear cells were obtained from patients before beginning androgen
      deprivation therapy (ADT) and at several time points thereafter. These cells were
      analyzed for the frequency of specific lymphocyte populations and their response
      to stimulation. The development of prostate antigen-specific immune responses was
      assessed using SEREX (serological identification of antigens by recombinant
      expression). Patients developed expansion of the naive T-cell compartment
      persisting over the course of androgen deprivation, together with an increase in
      effector-cell response to stimulation, and the generation of prostate tissue
      associated IgG antibody responses, implying a potential benefit to the use of ADT
      in combination with prostate cancer-directed immunotherapies. The optimal timing
      and sequence of androgen deprivation with immune-based therapies awaits future
      experimental evaluation.

PMID- 20153398
TI  - Dopaminergic drugs, paraphilic fantasies, paraphilic behaviours and creativity in
      Parkinson's disease.

PMID- 20153397
TI  - Immune "tolerance profiles" in donor bone marrow infused kidney transplant
      patients using multiple ex vivo functional assays.
AB  - Ex vivo identification of donor-specific unresponsiveness in organ transplant
      recipients is important for immunosuppression (IS) minimization. We tested three
      groups of stable living, related-donor kidney transplant patients up to 11 years
      postoperatively, i.e., 20 haploidenticals with donor bone marrow cell (DBMC)
      infusions, eight noninfused haploidentical controls (haplo controls), and 11 HLA
      identical controls (HLA-id), using multiple ex vivo immune assays. We observed
      that no patients developed donor-specific antibodies. The majority showed donor
      specific CTL unresponsiveness from year 1 onward. Thirteen of 20 DBMC recipients
      became specifically donor MLR nonreactive. Depletion of donor cells in DBMC
      recipients still MLR reactive increased donor-specific reactivity by 75% +/- 36%
      (p = 0.04). Adding them back in low concentration caused antigen specific
      inhibition. The frequencies of ELISPOT granzyme-B and interferon-gamma-producing
      cells somewhat paralleled the CTL and MLR responses. In the trans vivo DTH, 14 of
      19 DBMC recipients demonstrated donor-specific unresponsiveness and 16 of 19
      showed "linked suppression," vs none of eight and one of eight haplo controls and
      vs six of 10 and one of 10 HLA-ids, respectively. Most importantly, when all six
      assays were performed simultaneously, 10 of 18 DBMC, five of 10 HLA-ids, and no
      haplo controls were specifically donor unresponsive long term. We propose that a
      cluster analysis combining these assays will reveal tolerant recipients in whom
      IS minimization may safely be tested. This appears to have occurred in many DBMC
      infused recipients.

PMID- 20153400
TI  - Hypoxia-preconditioned adipose tissue-derived mesenchymal stem cell increase the
      survival and gene expression of engineered neural stem cells in a spinal cord
      injury model.
AB  - Hypoxic preconditioning (HP) is a novel strategy to make stem cells resistant to
      the ischemic environment they encounter after transplantation into injured
      tissue; this strategy improves survival of both the transplanted cells and the
      host cells at the injury site. Using both in vitro and in vivo injury models, we
      confirmed that HP-treated adipose tissue-derived mesenchymal stem cells (HP-AT
      MSCs) increased cell survival and enhanced the expression of marker genes in
      DsRed-engineered neural stem cells (NSCs-DsRed). Similar to untreated AT-MSCs, HP
      AT-MSCs had normal morphology and were positive for the cell surface markers
      CD90, CD105, and CD29, but not CD31. In three in vitro ischemic-mimicking injury
      models, HP-AT-MSCs significantly increased both the viability of NSCs-DsRed and
      the expression of DsRed and clearly reduced the number of annexin-V-positive
      apoptotic NSCs-DsRed and the expression of the apoptotic factor Bax. Consistent
      with the in vitro assay, co-transplantation of NSCs-DsRed with HP-AT-MSCs
      significantly improved the survival of the NSCs-DsRed, resulting in an increased
      expression of the DsRed reporter gene at the transplantation site in a rat spinal
      cord injury (SCI) model. These findings suggest that the co-transplantation of HP
      AT-MSCs with engineered NSCs can improve both the cell survival and the gene
      expression of the engineered NSCs, indicating that this novel strategy can be
      used to augment the therapeutic efficacy of combined stem cell and gene therapies
      for SCI.

PMID- 20153399
TI  - Kupffer cells participate in 2-butoxyethanol-induced liver hemangiosarcomas.
AB  - 2-Butoxyethanol increases hemangiosarcomas selectively in male mouse liver after
      chronic inhalation through mechanisms that have not fully been elucidated.
      Hemolysis, a primary toxic effect associated with 2-butoxyethanol exposure in
      rodents, increased hemosiderin (iron) deposition in Kupffer cells in the liver.
      These findings, along with the induction of hepatic neoplastic lesions, led to
      our hypothesis that the induction hemangiosarcomas by 2-butoxyethanol is due to
      the activation of Kupffer cells, subsequent to hemolysis, that results in the
      induction of DNA synthesis in target cells (endothelial cells); allowing for the
      selective proliferation of preneoplastic target cells and/or the promotion of new
      initiated cells. The present studies were conducted to determine whether Kupffer
      cells contributed to 2-butoxyethanol-induced endothelial DNA synthesis in the
      liver, thereby determining whether a linkage exists between these events. Male
      B6C3F1 mice were treated with 450 and 900 mg/kg 2-butoxyethanol (via daily
      gavage; 5x/week) for 7 days in the presence or absence of Kupffer cell depletion
      (via clodronate-encapsulated liposomes). 2-Butoxyethanol (450 and 900 mg/kg/day)
      increased the number of F4/80 stained cells (Kupffer cells) compared to controls
      (approximately 1.3- and approximately 1.6-fold over control, respectively).
      Clodronate liposome treatment reduced the number of Kupffer cells by >90%, as
      assessed by F4/80 immunohistochemistry. Increased hemolysis, measured by
      increases in relative spleen weights and decreased hematocrit was confirmed in 2
      butoxyethanol treated mice. The percentage of iron-stained endothelial cells
      increased by approximately 11-fold over control, and endothelial cell DNA
      synthesis increased approximately 1.7-fold over control in 2-butoxyethanol
      exposed mice. Importantly, Kupffer cell depletion reduced 2-butoxyethanol-induced
      iron staining and hepatic endothelial cell DNA synthesis. These studies provide
      evidence supporting the hypothesis that the Kupffer cell modulates 2
      butoxyethanol-induced endothelial cell DNA synthesis, and therefore may
      contribute to hemangiosarcoma induction by 2-butoxyethanol.

PMID- 20153401
TI  - Radiolabelled proteins for positron emission tomography: Pros and cons of
      labelling methods.
AB  - BACKGROUND: Dynamic biomedical research is currently yielding a wealth of
      information about disease-associated molecular alterations on cell surfaces and
      in the extracellular space. The ability to visualize and quantify these
      alterations in vivo could provide important diagnostic information and be used to
      guide individually-optimized therapy. Biotechnology can provide proteinaceous
      molecular probes with highly specific target recognitions. Suitably labelled,
      these may be used as tracers for radionuclide-based imaging of molecular disease
      signatures. If the labels are positron-emitting radionuclides, the superior
      resolution, sensitivity and quantification capability of positron emission
      tomography (PET) can be exploited. SCOPE OF REVIEW: This article discusses
      different approaches to labelling proteins with positron-emitting nuclides with
      suggestions made depending on the biological features of the tracers. MAJOR
      CONCLUSIONS: Factors such as matching biological and physical half-lives,
      availability of the nuclide, labelling yields, and influences of labelling on
      targeting properties (affinity, charge and lipophilicity, cellular processing and
      retention of catabolites) should be considered when selecting a labelling
      strategy for each proteinaceous tracer. GENERAL SIGNIFICANCE: The labelling
      strategy used can make all the difference between success and failure in a tracer
      application. This review emphasises chemical, biological and pharmacological
      considerations in labelling proteins with positron-emitting radionuclides.

PMID- 20153402
TI  - The effects of alcoholism on the human basolateral amygdala.
AB  - Alcohol affects gene expression in several brain regions. The amygdala is a key
      structure in the brain's emotional system and in recent years the crucial
      importance of the amygdala in drug-seeking and relapse has been increasingly
      recognized. In this study gene expression screening was used to identify genes
      involved in alcoholism in the human basolateral amygdala of male patients. The
      results show that alcoholism affects a broad range of genes and many systems
      including genes involved in synaptic transmission, neurotransmitter transport,
      structural plasticity, metabolism, energy production, transcription and RNA
      processing and the circadian cycle. In particular, genes involved in the
      glutamate system were affected in the alcoholic patients. In the amygdala the
      glutamate system is involved in the acquisition, consolidation, expression and
      extinction of associative learning, which is a vital part of addiction, and in
      alcohol abusers it is associated with withdrawal anxiety and neurodegeneration.
      Downregulation of the excitatory amino acid transporters GLAST, GLT-1 and the
      AMPA glutamate receptor 2 (GluR2) revealed by the microarray were confirmed by
      Western blots. The decreased expression of GLAST, GLT-1 and GluR2 in the
      alcoholic patients may increase glutamate tone and activity in the basolateral
      amygdala and this may contribute to neurodegeneration as well as the expression
      of associative memories and anxiety which underlie continued drug-seeking and
      chronic relapse.

PMID- 20153403
TI  - Calcium and cAMP signaling induced by gamma-hydroxybutyrate receptor(s)
      stimulation in NCB-20 neurons.
AB  - The NCB-20 neurohybridoma cells differentiated with dibutyryl-cyclic-AMP
      represent an interesting model to study several components of the gamma
      hydroxybutyrate (GHB) system in brain. In particular, an active Na(+)-dependent
      uptake and a depolarization-evoked release of GHB is expressed by these cells,
      together with high affinity specific binding sites for this substance. However,
      only little is known about cellular mechanisms following GHB receptor(s)
      stimulation in these neurons. Electrophysiological data indicate that GHB can
      differently affect Ca(2+) currents. L-type calcium channels were typically
      inhibited by GHB when NCB-20 cells were depolarized. In contrast, when NCB-20
      cells were at resting potential, GHB induced a specific Ca(2+) entry through T
      type calcium channels. In this study, we investigated the effect induced on
      cytosolic free Ca(2+) level and cAMP production by GHB receptor(s) stimulated
      with micromolar concentrations of GHB or structural analogues of GHB. Ca(2+)
      movements studied by cellular imaging were dose-dependently increased but
      disappeared for GHB concentrations >25 microM. In addition, nanomolar doses of
      GHB inhibited forskolin-stimulated adenylate cyclase. This effect was also
      rapidly desensitized at higher GHB concentrations. Acting as an antagonist, NCS
      382 decreased GHB receptor(s) mediated cAMP and calcium signals. The agonist NCS
      356 mimicked GHB effects which were not affected by the GABA(B) receptor
      antagonist CGP-55-845. Our results reveal the occurrence of Ca(2+)-dependent
      adenylate cyclase inhibition in NCB-20 neurons after GHB receptor(s) stimulation
      by GHB concentrations <50 microM. Above this dose, GHB effects were inactivated.
      In addition, at GHB concentrations exceeding 50 microM, GTP-gammaS binding was
      also reduced, confirming the desensitization of GHB receptor(s). Taken together,
      these results support the existence in NCB-20 neurons of GHB receptors belonging
      to GPCR family that may recruit various G protein subtypes.

PMID- 20153404
TI  - Higher order structure of aquaporin-4.
AB  - Unlike other mammalian AQPs, multiple tetramers of AQP4 associate in the plasma
      membrane to form peculiar structures called Orthogonal Arrays of Particles
      (OAPs), that are observable by freeze-fracture electron microscopy (FFEM).
      However, FFEM cannot give information about the composition of OAPs of different
      sizes, and due to its technical complexity is not easily applicable as a routine
      technique. Recently, we employed the 2D gel electrophoresis BN-SDS/PAGE that for
      the first time enabled the biochemical isolation of AQP4-OAPs from several
      tissues. We found that AQP4 protein is present in several higher-order complexes
      (membrane pools of supra-structures) which contain different ratios of M1/M23
      isoforms corresponding to AQP4-OAPs of different size. In this paper, we
      illustrate in detail the potentiality of 2D BN/SDS-PAGE for analyzing AQP4 supra
      structures, their relationship with the dystrophin glycoprotein complex and other
      membrane proteins, and their role as a specific target of Neuromyelitis Optica
      autoantibodies.

PMID- 20153405
TI  - Mesenchymal stem cells inhibition of chronic ethanol-induced oxidative damage via
      upregulation of phosphatidylinositol-3-kinase/Akt and modulation of extracellular
      signal-regulated kinase 1/2 activation in PC12 cells and neurons.
AB  - It is well known that chronic ethanol consumption damages CNS through oxidative
      stress which results in many dysfunctions. Recently, it has been demonstrated
      that as a promising strategy to treat several neurological diseases, transplanted
      bone marrow-derived mesenchymal stem cells (MSCs) can secrete lots of protective
      factors that in turn promote function recovery. In the present study, we assessed
      the potential effects of MSCs conditioned medium (MSC-CM) against chronic ethanol
      associated damage on PC12 cells and primary cortical neurons. We found that
      pretreatment with MSC-CM notably improved cell survival, prevented chronic
      ethanol-associated apoptosis and abolished the robust deterioration in oxidative
      status. In addition, we also discovered that chronic ethanol exposure induced an
      inactivation of phosphatidylinositol-3-kinase (PI3K)/Akt and a lasting activation
      of extracellular signal-regulated kinase 1/2 (ERK1/2) in both PC12 cells and
      primary cortical neurons which were able to be reversed by MSC-CM. The PI3K
      inhibitor (LY294002) was able to reduce the antioxidative and cytoprotective
      effects conferred by MSC-CM, in part, and the ERK1/2 inhibitor (PD98059) was able
      to elicit significant protection from chronic ethanol cytotoxicity but not rescue
      the deterioration in oxidative status induced by chronic ethanol. Taken together,
      these findings provide the first evidence that MSCs might have potent antioxidant
      action to shield the apoptotic impairment from chronic ethanol exposure in PC12
      cells and neurons, which is involved in upregulation of PI3K/Akt and modulation
      of ERK1/2 activation, at least partially.

PMID- 20153406
TI  - Expertise with pathological actions modulates a viewer's motor system.
AB  - Brain mechanisms for action understanding rely on matching the observed actions
      into the viewer's motor system. Health professionals, who treat patients affected
      by movement disorders as dystonia, frequently see hyperkinetic action patterns
      characterized by an overflow of muscle co-contractions. To avert an overload of
      the motor system during observation of those actions, they might need to look at
      dystonic motor symptoms in a cool, detached way. To investigate whether visual
      expertise about atypical movement kinematics influences the viewer's motor
      system, we applied transcranial magnetic stimulation to clinicians and to naive
      subjects, while they observed handwriting actions performed with two different
      kinematics: fluent and non-fluent. Crucially, the latter movement pattern was
      easily recognized by the clinicians as a typical expression of writer's cramp,
      whereas it was unknown to the naive subjects. Results showed that clinicians had
      similar corticospinal activation during observation of dystonic and healthy
      writings, whereas naive subjects were hyper-activated during observation of
      dystonic movements. Hyper-activation was selective for the muscles directly
      involved in the dystonic co-contractions and inversely correlated with subjective
      movement fluency scores, hinting at a fine-tuned association between the
      breakdown of observed movement fluency and corticospinal activation. These
      findings suggest that observation of unusual pathological actions differently
      modulates the viewer's motor system, depending on knowledge, visual expertise,
      and ability in recognizing suboptimal movement kinematics.

PMID- 20153407
TI  - Ethanol ingestion affects flight performance and echolocation in Egyptian fruit
      bats.
AB  - Ethanol, a potential toxin for vertebrates, is present in all fleshy fruits and
      its content increases as the fruit ripens. Previously, we found that the marginal
      value of food for Egyptian fruit bats, Rousettus aegyptiacus, decreases when its
      ethanol content exceeds 1%. Therefore, we hypothesized that, if ingested, food
      containing >1% ethanol is toxic to these bats, probably causing inebriation that
      will affect flight and echolocation skills. We tested this hypothesis by flying
      Egyptian fruit bats in an indoor corridor and found that after ingesting ethanol
      rich food bats flew significantly slower than when fed ethanol-free food. Also,
      the ingestion of ethanol significantly affected several variables of the bats'
      echolocation calls and behavior. We concluded that ethanol can be toxic to fruit
      bats; not only does it reduce the marginal value of food, but it also has
      negative physiological effects on their ability to fly competently and on their
      calling ability.

PMID- 20153408
TI  - Some effects of procedural variables on operant choice behavior.
AB  - Procedural variables are concerned with the way subjects contact stimulus,
      response, and reinforcer variables and relations in an experiment. Procedural
      variables may therefore be understood as tools that allow researchers and
      theorists to explore the generality of their conceptions of independent
      variables, behavioral processes, and quantitative laws of behavior. The present
      article reviews data from several studies showing how procedural variables can
      influence the outcome of operant choice experiments, even when nominal
      independent variables remain constant. An important theoretical issue raised by
      these data is whether researchers have most usefully identified the independent
      variables that they incorporate into their quantitative models. Particular
      attention is paid to how procedural variables can influence the measure of
      reinforcement frequency over time that best correlates with the distribution of
      choice responding over time.

PMID- 20153409
TI  - The impact of fossil calibrations, codon positions and relaxed clocks on the
      divergence time estimates of the native Australian rodents (Conilurini).
AB  - The native rodents are the most species-rich placental mammal group on the
      Australian continent. Fossils of native Australian rodents belonging to the group
      Conilurini are known from Northern Australia at 4.5Ma. These fossil assemblages
      already display a rich diversity of rodents, but the exact timing of their
      arrival on the Australian continent is not yet established. The complete
      mitochondrial genomes of two native Australian rodents, Leggadina lakedownensis
      (Lakeland Downs mouse) and Pseudomys chapmani (Western Pebble-mound mouse) were
      sequenced for investigating their evolutionary history. The molecular data were
      used for studying the phylogenetic position and divergence times of the
      Australian rodents, using 12 calibration points and various methods. Phylogenetic
      analyses place the native Australian rodents as the sister-group to the genus
      Mus. The Mus-Conilurini calibration point (7.3-11.0Ma) is highly critical for
      estimating rodent divergence times, while the influence of the different
      algorithms on estimating divergence times is negligible. The influence of the
      data type was investigated, indicating that amino acid data are more likely to
      reflect the correct divergence times than nucleotide sequences. The study on the
      problems related to estimating divergence times in fast-evolving lineages such as
      rodents, emphasize the choice of data and calibration points as being critical.
      Furthermore, it is essential to include accurate calibration points for fast
      evolving groups, because the divergence times can otherwise be estimated to be
      significantly older. The divergence times of the Australian rodents are highly
      congruent and are estimated to 6.5-7.2Ma, a date that is compatible with their
      fossil record.

PMID- 20153410
TI  - Methylmercury chloride induces alveolar type II epithelial cell damage through an
      oxidative stress-related mitochondrial cell death pathway.
AB  - Mercury, one of the widespread pollutants in the world, induces oxidative stress
      and dysfunction in many cell types. Alveolar type II epithelial cells are known
      to be vulnerable to oxidative stress. Alveolar type II epithelial cells produce
      and secrete surfactants to maintain morphological organization, biophysical
      functions, biochemical composition, and immunity in lung tissues. However, the
      precise action and mechanism of mercury on alveolar type II epithelial cell
      damage remains unclear. In this study, we investigate the effect and possible
      mechanism of methylmercury chloride (MeHgCl) on the human lung invasive carcinoma
      cell line (Cl1-0) and mouse lung tissue. Cl1-0 cells were exposed to MeHgCl (2.5
      10 microM) for 24-72 h. The results showed a decrease in cell viability and an
      increase in malondialdehyde (MDA) level and ROS production at 72 h after MeHgCl
      exposure in a dose-dependent manner. Caspase-3 activity, sub-G1 contents and
      annexin-V binding were dramatically enhanced in Cl1-0 cells treated with MeHgCl.
      MeHgCl could also activate Bax, release cytochrome c, and cleave poly(ADP-Ribose)
      polymerase (PARP), and decrease surfactant proteins mRNA levels. Moreover, in
      vivo study showed that mercury contents of blood and lung tissues were
      significantly increased after MeHgCl treatment in mice. The MDA levels in plasma
      and lung tissues were also dramatically raised after MeHgCl treatment. Lung
      tissue sections of MeHgCl-treated mice showed pathological fibrosis as compared
      with vehicle control. The mRNA levels of proteins in apoptotic signaling,
      including p53, mdm-2, Bax, Bad, and caspase-3 were increased in mice after
      exposure to MeHgCl. In addition, the mRNA levels of surfactant proteins (SPs),
      namely, SP-A, SP-B, SP-C, and SP-D (alveolar epithelial cell functional markers)
      were significantly decreased. These results suggest that MeHgCl activates an
      oxidative stress-induced mitochondrial cell death in alveolar epithelial cells.

PMID- 20153411
TI  - Crotonaldehyde induces oxidative stress and caspase-dependent apoptosis in human
      bronchial epithelial cells.
AB  - Crotonaldehyde is a widespread environmental pollutant and lipid peroxidation
      product. Crotonaldehyde is a risk factor for many diseases (e.g., chronic
      pulmonary inflammation). However, its toxicity and its mechanism of action have
      not been thoroughly investigated. The purpose of this study is to investigate
      crotonaldehyde-induced oxidative stress and mechanism of cell death in BEAS-2B
      cells. Crotonaldehyde caused decreases of intracellular reduced glutathione
      levels and increases of reactive oxygen species in a dose-dependent manner.
      Crotonaldehyde induced cell death by apoptosis, and gradually transitioned to
      necrosis at high dose of crotonaldehyde, as demonstrated by Annexin V-FITC/PI
      staining and cell morphology analysis. Crotonaldehyde-induced ATP decline
      observed in the study might partially account for the switch from apoptosis to
      necrosis. Mitochondria membrane potential, cytochrome c release, caspase-9, and
      caspase-3/7 activity were investigated, and the results suggest that
      crotonaldehyde-induced apoptosis was activated in a caspase-dependent way.
      Collectively, these results demonstrate crotonaldehyde induces cell oxidative
      stress and caspase-dependent apoptosis.

PMID- 20153412
TI  - Cell-specific targeting in the mouse inner ear using nanoparticles conjugated
      with a neurotrophin-derived peptide ligand: potential tool for drug delivery.
AB  - Cell specific targeting is an emerging field in nanomedicine. Homing of the
      multifunctional nanoparticles (MFNPs) is achieved by the conjugation of targeting
      moieties on the nanoparticle surface. The inner ear is an attractive target for
      new drug delivery strategies as it is hard to access and hearing loss is a
      significant worldwide problem. In this work we investigated the utility of a
      Nerve Growth Factor-derived peptide (hNgf_EE) functionalized nanoparticles (NPs)
      to target cells of the inner ear. These functionalized NPs were introduced to
      organotypic explant cultures of the mouse inner ear and to PC-12 rat
      pheochromocytoma cells. The NPs did not show any signs of toxicity. Specific
      targeting and higher binding affinity to spiral ganglion neurons, Schwann cells
      and nerve fibers of the explant cultures were achieved through ligand mediated
      multivalent binding to tyrosine kinase receptors and to p75 neurotrophin
      receptors. Unspecific uptake of NPs was investigated using NPs conjugated with
      scrambled hNgf_EE peptide. Our results indicate a selective cochlear cell
      targeting by MFNPs, which may be a potential tool for cell specific drug and gene
      delivery to the inner ear.

PMID- 20153413
TI  - PEG-benzofulvene copolymer hydrogels for antibody delivery.
AB  - Poly[monomethylnona(ethylene glycol) 1-methylene-3-(4-methylphenyl)-1H-indene-2
      carboxylate] (poly-1b) a new polymer based on a PEG-functionalized benzofulvene
      macromonomer have been investigated as hydrogel-based material for complexation
      and release of immunoglobulin (IgG) at physiological mimicking conditions. The
      polymer ability to complex human IgG has been studied by preparing
      copolymer/protein complexes obtained by spontaneous protein interactions onto
      polymer hydrogel aggregates, and the protein release rate has been evaluated at
      physiological conditions. SEM analysis was used to visualize the copolymer/IgG
      aggregates and its microstructured deposition. Moreover, rheological studies
      performed at 37 degrees C allowed determining hydrogel mechanical properties. On
      the basis of these information and NMR transverse relaxation measurements, the
      estimation of hydrogel mesh size distribution was possible. Finally, biological
      studies performed with poly-1b aqueous dispersions showed no cytotoxic effect on
      MCF-7 cell line, suggesting potential biocompatibility features for this polymer
      and making this new polymer a good potential candidate for the production of drug
      delivery systems.

PMID- 20153414
TI  - SLN for topical application in skin diseases--characterization of drug-carrier
      and carrier-target interactions.
AB  - The modes of drug-particle interactions considerably influence drug delivery by
      nanoparticulate carrier systems and drug penetration into the skin. The exact
      mechanism of the drug loading and its release are still ambiguous. Therefore, the
      loading process, the interaction of the agent and the lipid matrix of solid lipid
      nanoparticles (SLNs) as well as the uptake of the loaded agent by skin lipids
      were analysed by electron spin resonance (ESR) and parelectric spectroscopy (PS)
      using spin probes (TEMPO, TEMPOL, and CAT-1) as model drugs differing in their
      lipophilicity. The spin probes were closely attached to the particles lipid
      surface (TEMPO) or located in the layers of the surfactant (CAT-1), respectively.
      Furthermore, two distinct sub-compartments on the SLN were found. To simulate the
      processes at the phase boundary SLN dispersion/skin, skin lipid mixtures were
      prepared and the transfer process of the spin labels was followed by ESR
      tomography. Transfer rates were related to the lipophilicity of the spin probe,
      the lipid mixture and the applied pharmaceutical formulation, SLN dispersion and
      aqueous solution, respectively. In particular, SLN accelerated in particular the
      distribution of the lipophilic agents.

PMID- 20153415
TI  - Fermentation of lactose to bio-ethanol by yeasts as part of integrated solutions
      for the valorisation of cheese whey.
AB  - Cheese whey, the main dairy by-product, is increasingly recognized as a source of
      many bioactive valuable compounds. Nevertheless, the most abundant component in
      whey is lactose (ca. 5% w/v), which represents a significant environmental
      problem. Due to the large lactose surplus generated, its conversion to bio
      ethanol has long been considered as a possible solution for whey bioremediation.
      In this review, fermentation of lactose to ethanol is discussed, focusing on wild
      lactose-fermenting yeasts, particularly Kluyveromyces marxianus, and recombinant
      Saccharomyces cerevisiae strains. The early efforts in the screening and
      characterization of the fermentation properties of wild lactose-consuming yeasts
      are reviewed. Furthermore, emphasis is given on the latter advances in
      engineering S. cerevisiae strains for efficient whey-to-ethanol bioprocesses.
      Examples of industrial implementation are briefly discussed, illustrating the
      viability of whey-to-ethanol systems. Current developments on strain engineering
      together with the growing market for biofuels will likely boost the industrial
      interest in such processes.

PMID- 20153416
TI  - Knockdown of COPA, identified by loss-of-function screen, induces apoptosis and
      suppresses tumor growth in mesothelioma mouse model.
AB  - Malignant mesothelioma is a highly aggressive tumor arising from serosal surfaces
      of the pleura and is triggered by past exposure to asbestos. Currently, there is
      no widely accepted treatment for mesothelioma. Development of effective drug
      treatments for human cancers requires identification of therapeutic molecular
      targets. We therefore conducted a large-scale functional screening of
      mesothelioma cells using a genome-wide small interfering RNA library. We
      determined that knockdown of 39 genes suppressed mesothelioma cell proliferation.
      At least seven of the 39 genes-COPA, COPB2, EIF3D, POLR2A, PSMA6, RBM8A, and
      RPL18A-would be involved in anti-apoptotic function. In particular, the COPA
      protein was highly expressed in some mesothelioma cell lines but not in a pleural
      mesothelial cell line. COPA knockdown induced apoptosis and suppressed tumor
      growth in a mesothelioma mouse model. Therefore, COPA may have the potential of a
      therapeutic target and a new diagnostic marker of mesothelioma.

PMID- 20153417
TI  - Identification of human specific gene duplications relative to other primates by
      array CGH and quantitative PCR.
AB  - In order to identify human lineage specific (HLS) copy number differences (CNDs)
      compared to other primates, we performed pair wise comparisons (human vs.
      chimpanzee, gorilla and orangutan) by using cDNA array comparative genomic
      hybridization (CGH). A set of 23 genes with HLS duplications were identified, as
      well as other lineage differences in gene copy number specific of chimpanzee,
      gorilla and orangutan. Each species has gained more copies of specific genes
      rather than losing gene copies. Eleven of the 23 genes have only been observed to
      have undergone HLS duplication in Fortna et al. (2004) and in the present study.
      Then, seven of these 11 genes were analyzed by quantitative PCR in chimpanzee,
      gorilla and orangutan, as well as in other six primate species (Hylobates lar,
      Cercopithecus aethiops, Papio hamadryas, Macaca mulatta, Lagothrix lagothricha,
      and Saimiri sciureus). Six genes confirmed array CGH data, and four of them
      appeared to have bona fide HLS duplications (ABCB10, E2F6, CDH12, and TDG genes).
      We propose that these gene duplications have a potential to contribute to
      specific human phenotypes.

PMID- 20153418
TI  - Chronic stress alters the density and morphology of microglia in a subset of
      stress-responsive brain regions.
AB  - The current study, in parallel experiments, evaluated the impact of chronic
      psychological stress on physiological and behavioural measures, and on the
      activation status of microglia in 15 stress-responsive brain regions. Rats were
      subjected, for 14 days, to two 30 min sessions of restraint per day, applied at
      random times each day. In one experiment the effects of stress on sucrose
      preference, weight gain, core body temperature, and struggling behaviour during
      restraint, were determined. In the second experiment we used immunohistochemistry
      to investigate stress-induced changes in ionized calcium-binding adaptor molecule
      1 (Iba1), a marker constitutively expressed by microglia, and major
      histocompatibility complex-II (MHC-II), a marker often expressed on activated
      microglia, in a total of 15 stress-responsive nuclei. We also investigated
      cellular proliferation in these regions using Ki67 immunolabelling, to check for
      the possibility of microglial proliferation. Collectively, the results we
      obtained showed that chronic stress induced a significant increase in anhedonia,
      a decrease in weight gain across the entire observation period, a significant
      elevation in core body temperature during restraint, and a progressive decrease
      in struggling behaviour within and over sessions. With regard to microglial
      activation, chronic stress induced a significant increase in the density of Iba1
      immunolabelling (nine of 15 regions) and the number of Iba1-positive cells (eight
      of 15 regions). Within the regions that exhibited an increased number of Iba1
      positive cells after chronic stress, we found no evidence of a between group
      difference in the number of MHC-II or Ki67 positive cells. In summary, these
      results clearly demonstrate that chronic stress selectively increases the number
      of microglia in certain stress-sensitive brain regions, and also causes a marked
      transition of microglia from a ramified-resting state to a non-resting state.
      These findings are consistent with the view that microglial activation could play
      an important role in controlling and/or adapting to stress.

PMID- 20153419
TI  - Expression profile of multiple secretory phospholipase A(2) isoforms in the rat
      CNS: enriched expression of sPLA(2)-IIA in brainstem and spinal cord.
AB  - Phospholipases A(2) (PLA(2)) are enzymes which cleave the sn-2 ester bond in
      membrane phospholipids to release free fatty acids and lysophospholipids. The
      present study aimed to elucidate the expression profile of multiple secretory
      phospholipase A(2) (sPLA(2)) isoforms in the normal rat CNS with focus on sPLA(2)
      IIA in the brainstem and spinal cord. Quantitative RT-PCR analysis showed that
      sPLA(2)-IB expression was low throughout the CNS, sPLA(2)-IIA expression was high
      in the brainstem and spinal cord, sPLA(2)-IIC expression was high in the cerebral
      neocortex, hippocampus and thalamus/hypothalamus, sPLA(2)-V expression was high
      in the olfactory bulb and cerebellum, and sPLA(2)-X was expressed at very low
      levels in the normal CNS. Of the isoforms, sPLA(2)-IIA mRNA expression was
      highest in the brainstem and spinal cord suggesting that this could be the most
      relevant isoform in the ascending pain pathway. Western blot analysis showed high
      level of sPLA(2)-IIA expression in the brainstem and cervical, thoracic and
      lumbar spinal segments but low level of expression in other parts of the brain.
      sPLA(2)-IIA was localized by immunohistochemistry to the spinal trigeminal and
      facial motor nuclei and dorsal- and ventral-horns of the spinal cord. The enzyme
      was found on the endoplasmic reticulum of neuronal cell bodies and small diameter
      dendrites or dendritic spines at electron microscopy. The expression of sPLA(2)
      IIA in the dorsal horn and spinal trigeminal nucleus is consistent with previous
      results which showed an important role of CNS sPLA(2) in nociceptive
      transmission.

PMID- 20153420
TI  - Extracardiac ice formation during cryoballoon technique for atrial fibrillation.

PMID- 20153421
TI  - Essentials on qualitative research methods: clinical considerations for allied
      professionals.

PMID- 20153422
TI  - Early repolarization associated with sudden death: insights from noninvasive
      electrocardiographic imaging.

PMID- 20153423
TI  - Chronic exposure to cadmium and arsenic strongly influences concentrations of 8
      oxo-7,8-dihydro-2'-deoxyguanosine in urine.
AB  - Exposure to arsenic (As), cadmium (Cd), and lead (Pb) may generate oxidative
      stress, which can be assessed by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in
      urine, a sensitive marker of oxidatively damaged DNA. We have evaluated oxidative
      stress induced by chronic mixed exposure to As, Cd, and Pb, as well as the
      influence of As metabolism and nutritional status, i.e., levels of ferritin (Ft),
      selenium (Se), zinc (Zn), and manganese (Mn) and body weight. 8-OxodG was
      measured in urine from 212 women in early pregnancy from Matlab, in rural
      Bangladesh, using LC-MS/MS. Cd and Pb were analyzed in urine and erythrocytes,
      and Se, Mn, and Zn were analyzed in erythrocytes, all by ICPMS. As and As
      metabolites were analyzed in urine by HPLC-ICPMS. Ferritin was analyzed in plasma
      by radioimmunoassay. The median concentration of 8-oxodG was 8.3 nmol/L (adjusted
      for specific gravity), range 1.2-43, corresponding to a median of 4.7 microg/g
      creatinine, range 1.8-32. 8-OxodG was positively associated with urinary Cd
      (beta=0.32, p< 0.001), urinary As (beta=0.0007, p=0.001), the fraction of the
      monomethylated arsenic metabolite in urine (beta=0.0026, p=0.004), and plasma Ft
      (beta=0.20, p< 0.001). A joint effect was seen for urinary Cd and As, but whether
      this effect was additive or multiplicative was difficult to discern.

PMID- 20153424
TI  - Neonatal methamphetamine-induced corticosterone release in rats is inhibited by
      adrenal autotransplantation without altering the effect of the drug on
      hippocampal serotonin.
AB  - Rat neonatal methamphetamine exposure results in corticosterone release and
      learning and memory impairments in later life; effects also observed after
      neonatal stress. Previous attempts to test the role of corticosterone release
      after methamphetamine using corticosterone inhibitors were unsuccessful and
      adrenalectomy caused reductions in hippocampal serotonin greater than those
      caused by methamphetamine alone. Here we tested whether adrenal
      autotransplantation could be used to attenuate methamphetamine-induced
      corticosterone release without also altering the effects of the drug on
      serotonin. Adrenal autotransplantation surgery occurred on postnatal day 9
      followed by methamphetamine or saline treatment from postnatal day 11-20
      (10mg/kg/dosex4/day). Plasma corticosterone and hippocampal serotonin and 5
      hydroxyindoleacetic acid were determined 30min following the first treatment on
      each day between postnatal days 11-20. Adrenal autotransplantation attenuated
      neonatal methamphetamine-induced corticosterone release by approximately 70%
      initially, approximately 55% midway through treatment, and approximately 25% by
      the end of treatment. Methamphetamine reduced serotonin and 5-hydroxyindoleacetic
      acid in the hippocampus in the ADXA rats to the same degree as in SHAM rats. The
      data show that neonatal adrenal autotransplantation is an effective method for
      partially reducing treatment-induced corticosterone release while providing
      sufficient corticosterone to sustain normal growth and development. The method
      should be applicable to other models of developmental stress/corticosterone
      release.

PMID- 20153425
TI  - Neuroimmunomodulatory steroids in Alzheimer dementia.
AB  - Though pathobiochemical and neurochemical changes and accompanied morphological
      alterations in Alzheimer dementia are well known, the triggering mechanisms, if
      any, remain obscure. Important factors influencing the development and
      progression of Alzheimer disease include hormonal steroids and their metabolites,
      some of which may serve as therapeutic agents. This review focusses on major
      biochemical alterations in the brain of Alzheimer patients with respect to the
      involvement of steroids. It includes their role in impairment of fuel supply and
      in brain glycoregulation, with especial emphasis on glucocorticoids and their
      counter-regulatory steroids as dehydroepiandrosterone and its metabolites.
      Further, the role of steroids in beta-amyloid pathology is reviewed including
      alterations in tau-protein(s) phosphorylation. The (auto)immune theory of
      Alzheimer dementia is briefly outlined, pointing to the possible involvement of
      steroids in brain ageing, immunosenescence and neuronal apoptosis. Some effects
      of steroids are briefly mentioned on the formation and removal of reactive oxygen
      species and their effect on calcium flux and cytotoxicity. The recent biochemical
      research of Alzheimer disease focusses on molecular signalling at which steroids
      also take part. New findings may be anticipated when the mosaic describing the
      molecular mechanisms behind these events becomes more complete.

PMID- 20153426
TI  - Conversion of vitamin D3 to hormonally active 1alpha,25-dihydroxyvitamin D3 in
      cultured keratinocytes: relevance to cell growth and differentiation.
AB  - The regulatory potential of intracellularly generated calcitriol on growth and
      differentiation of cultured keratinocytes is determined by the degree of cell
      confluence and availability of the highly lipophilic substrate vitamin D3 to
      these cells. The enzymatic conversion of vitamin D3 to calcitriol is considerably
      elevated in the presence of the nontoxic surfactant copolymer pluronic F127 (120
      microg/ml medium) compared to the control without this agent. We found a positive
      correlation between the formation rate of calcitriol and inhibition of the 3H
      thymidine incorporation rate into the DNA of keratinocytes. Intracellularly
      generated calcitriol causes a clear increase of the cell diameter, and thus has a
      prodifferentiating effect on keratinocytes in vitro. These findings corroborate
      the hypothesis that UVB-induced production of vitamin D3 in human skin results in
      formation of substantial amounts of calcitriol in keratinocytes which suppress
      the growth and initiate differentiation of these cells.

PMID- 20153427
TI  - VDR microRNA expression and epigenetic silencing of vitamin D signaling in
      melanoma cells.
AB  - Malignant melanoma cells express the vitamin D receptor (VDR). However, some
      melanoma cell lines fail to respond to the antiproliferative effects of 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3). We reported previously that out of seven
      melanoma cell lines analyzed, three cell lines (MeWo, SK-Mel28, SM) respond to
      the antiproliferative effects of 1,25(OH)2D3, while the others (SK-Mel5, SK
      Mel25, IGR, Meljuso) are resistant. It was the aim of this study to investigate
      whether epigenetic mechanisms are of importance for the abrogation of vitamin D
      signaling in vitamin D resistant melanoma cells. We used the histone deacetylase
      inhibitor (HDACI) trichostatin A (TSA) and the DNA methyltransferase inhibitor
      (DNMTI) 5-azacytidine (5-Aza) to elucidate the effects of protein acetylation and
      of DNA hypermethylation on 1,25(OH)2D3-induced effects on cell proliferation,
      respectively. Additionally we analyzed the expression of VDR microRNA in
      1,25(OH)2D3-responding and resistant melanoma cells. TSA and 5-Aza exerted dose-
      and time-dependent antiproliferative effects on melanoma cell lines.
      Interestingly, combination therapy with 1,25(OH)2D3 and TSA exerted synergistic
      antiproliferative effects in a 1,25(OH)2D3-resistant melanoma cell line (IGR)
      (p<0.05). Combination therapy with 1,25(OH)2D3 and 5-Aza resulted in synergistic
      (MeWo after 72 h; p<0.05) or additive (other melanoma cell lines analyzed)
      antiproliferative effects. Additionally, we could show that VDR mRNA expression
      is relatively high in two of three 1,25(OH)2D3-responsive melanoma cells as
      compared to resistant cells, moreover this relatively high VDR expression is
      associated with low expression of miRNA125b in MeWo and SK-Mel28 cells. Our
      results suggest that the endogenous VDR mRNA level is inversely associated with
      expression of miRNA125b in melanoma cell lines analyzed. Moreover, miRNA125b may
      be involved in the regulation of VDR expression and in the resistance against
      1,25(OH)(2)D(3) in melanoma cells. It can be speculated whether miRNA125b may be
      of prognostic importance and/or may represent a therapeutic target for malignant
      melanoma. Drugs that influence epigenetic mechanisms might be promising
      therapeutics for the treatment of metastasized malignant melanoma, alone or in
      combination with antiproliferative or cytotoxic agents such as 1,25(OH)2D3.

PMID- 20153428
TI  - A genetic epilepsy rat model displays endophenotypes of psychosis.
AB  - The incidence of psychosis is increased in people with epilepsy, including
      idiopathic generalized epilepsies. To study the biological basis for this co
      morbidity, we compared GAERS, a genetic rat model of absence epilepsy, to non
      epileptic control rats (NEC). Mature, 14-week old GAERS showed enhanced
      amphetamine-induced locomotor hyperactivity - a feature also present in young (6
      week old) GAERS prior to epilepsy onset. Prepulse inhibition and its disruption
      by psychotropic drugs did not differ between strains, although GAERS displayed
      elevated startle responses at both epileptic and pre-epileptic ages. The
      frontoparietal cortex of GAERS displayed a twofold increase in the power of gamma
      (30-80 Hz) oscillations, a proposed neurophysiological correlate of psychosis.
      Radioligand binding autoradiography demonstrated reduced densities of dopamine
      transporters in the caudate nucleus and nucleus accumbens core and of dopamine D2
      receptors in the caudate nucleus. GAERS provide an opportunity to study the
      neurodevelopmental, genetic and therapeutic aspects of psychiatric comorbidities
      associated with epilepsy.

PMID- 20153429
TI  - Nano-interventions for neurodegenerative disorders.
AB  - With an increase in lifespan and changing population demographics, the incidence
      of central nervous system (CNS) diseases is expected to increase significantly in
      the 21st century. Contrary to common belief, it is recognized that
      neurodegenerative diseases may be multisystemic in nature and this presents
      numerous difficulties for the potential treatment of these disorders. This review
      focuses on applications in the nano-delivery of therapeutic agents across the
      blood-brain barrier. We explore various types of nanoparticles, ranging from
      polymerics to liposomes. A brief discussion of the pharmacokinetic parameters and
      specific targeting strategies of these nanoparticles follows, presenting
      suggestions for the mechanisms of cellular and intracellular uptake and possible
      toxicity considerations of nanoparticles.

PMID- 20153430
TI  - A new method for the purification of bioactive insulin-like growth factor-binding
      protein-3.
AB  - We present a novel efficient procedure for high level purification of human IGFBP
      3. Insulin-like growth factor-binding proteins (IGFBPs) are key regulators of
      insulin-like growth factor mediated signal transduction and thereby can
      profoundly influence cellular phenotypes. Certain IGFBPs, including IGFBP-3, have
      also been described to possess additional IGF-independent activities, which rely,
      at least in part, on their nuclear localization. However, the mechanisms of IGF
      independent biological activities of IGFBP-3 are not well understood. For the
      study of these functions, recombinant IGFBP-3 is used. However, it has
      traditionally been difficult to obtain recombinant protein in sufficient quality
      and quantity. Here we describe a new procedure for the purification of
      recombinant IGFBP-3 from cell culture supernatants involving a two-step affinity
      purification procedure. Using this new protocol, we obtained pure IGFBP-3 free of
      any visible contaminants. We also provide evidence that the protein purified in
      this way retains biological activity, to bind IGF and modulate IGF-dependent
      signal transduction. We also show that the purified protein produced by the new
      procedure is readily internalized by human fibroblasts, suggesting that this
      protein is also suitable to study intracellular trafficking of IGFBP-3.

PMID- 20153431
TI  - Expression and purification of a functional uric acid-xanthine transporter
      (UapA).
AB  - The Nucleobase-Ascorbate Transporters (NATs) family includes carriers with
      fundamental functions in uptake of key cellular metabolites, such as uric acid or
      vitamin C. The best studied example of a NAT transporter is the uric acid
      xanthine permease (UapA) from the model ascomycete Aspergillus nidulans. Detailed
      genetic and biochemical analyses have revealed much about the mechanism of action
      of this protein; however, the difficulties associated with handling eukaryotic
      membrane proteins have limited efforts to elucidate the precise structure
      function relationships of UapA by structural analysis. In this manuscript, we
      describe the heterologous overexpression of functional UapA as a fusion with GFP
      in different strains of Saccharomyces cerevisiae. The UapA-GFP construct
      expressed to 2.3 mg/L in a pep4Delta deletion strain lacking a key vacuolar
      endopeptidase and 3.8 mg/L in an npi1-1 mutant strain with defective Rsp5
      ubiquitin ligase activity. Epifluorescence microscopy revealed that the UapA-GFP
      was predominately localized to the plasma membrane in both strains, although a
      higher intensity of fluorescence was observed for the npi1-1 mutant strain plasma
      membrane. In agreement with these observations, the npi1-1 mutant strain
      demonstrated a approximately 5-fold increase in uptake of [(3)H]-xanthine
      compared to the pep4Delta deletion strain. Despite yielding the best results for
      functional expression, in-gel fluorescence of the UapA-GFP expressed in the npi1
      1 mutant strain revealed that the protein was subject to significant proteolytic
      degradation. Large scale expression of the protein using the pep4Delta deletion
      strain followed by purification produced mg quantities of pure, monodispersed
      protein suitable for further structural and functional studies. In addition, this
      work has generated a yeast cell based system for performing reverse genetics and
      other targeted approaches, in order to further understand the mechanism of action
      of this important model protein.

PMID- 20153432
TI  - Solution and electron microscopy characterization of lactococcal phage baseplates
      expressed in Escherichia coli.
AB  - We report here the characterization of several large structural protein complexes
      forming the baseplates (or part of them) of Siphoviridae phages infecting
      Lactococcus lactis: TP901-1, Tuc2009 and p2. We revisited a "block cloning"
      expression strategy and extended this approach to genomic fragments encoding
      proteins whose interacting partners have not yet been clearly identified.
      Biophysical characterization of some of these complexes using circular dichroism
      and size exclusion chromatography, coupled with on-line light scattering and
      refractometry, demonstrated that the over-produced recombinant proteins interact
      with each other to form large (up to 1.9MDa) and stable baseplate assemblies.
      Some of these complexes were characterized by electron microscopy confirming
      their structural homogeneity as well as providing a picture of their overall
      molecular shapes and symmetry. Finally, using these results, we were able to
      highlight similarities and differences with the well characterized much larger
      baseplate of the myophage T4.

PMID- 20153433
TI  - Recent advances in the production of proteins in insect and mammalian cells for
      structural biology.
AB  - The production of proteins in sufficient quantity and of appropriate quality is
      an essential pre-requisite for structural studies. Escherichia coli remains the
      dominant expression system in structural biology with nearly 90% of the
      structures in the Protein Data Bank (PDB) derived from proteins produced in this
      bacterial host. However, many mammalian and eukaryotic viral proteins require
      post-translation modification for proper folding and/or are part of large
      multimeric complexes. Therefore expression in higher eukaryotic cell lines from
      both invertebrate and vertebrate is required to produce these proteins. Although
      these systems are generally more time-consuming and expensive to use than
      bacteria, there have been improvements in technology that have streamlined the
      processes involved. For example, the use of multi-host vectors, i.e., containing
      promoters for not only E. coli but also mammalian and baculovirus expression in
      insect cells, enables target genes to be evaluated in both bacterial and higher
      eukaryotic hosts from a single vector. Culturing cells in micro-plate format
      allows screening of large numbers of vectors in parallel and is amenable to
      automation. The development of large-scale transient expression in mammalian
      cells offers a way of rapidly producing proteins with relatively high throughput.
      Strategies for selenomethionine-labelling (important for obtaining phase
      information in crystallography) and controlling glycosylation (important for
      reducing the chemical heterogeneity of glycoproteins) have also been reported for
      higher eukaryotic cell expression systems.

PMID- 20153434
TI  - Identification, characterization and genetic mapping of TLR1 loci in rainbow
      trout (Oncorhynchus mykiss).
AB  - Induction of innate immune pathways is critical for early anti-microbial defense
      but there is limited understanding of how teleosts recognize microbial molecules
      and activate these pathways. In mammals, Toll-like receptors (TLR) 1 and 2 form a
      heterodimer involved in recognizing peptidoglycans and lipoproteins of microbial
      origin. Herein, we identify and describe the rainbow trout (Oncorhynchus mykiss)
      TLR1 gene ortholog and its mRNA expression. Two TLR1 loci were identified from a
      rainbow trout bacterial artificial chromosome (BAC) library using DNA sequencing
      and genetic linkage analyses. Full length cDNA clone and direct sequencing of
      four BACs revealed an intact omTLR1 open reading frame (ORF) located on
      chromosome 14 and a second locus on chromosome 25 that contains a TLR1
      pseudogene. The duplicated trout loci exhibit conserved synteny with other fish
      genomes that extends beyond the TLR1 gene sequences. The omTLR1 gene includes a
      single large coding exon similar to all other described TLR1 genes, but unlike
      other teleosts it also has a 5' UTR exon and intron preceding the large coding
      exon. The omTLR1 ORF is predicted to encode an 808 amino-acid protein with 69%
      similarity to the Fugu TLR1 and a conserved pattern of predicted leucine-rich
      repeats (LRR). Phylogenetic analysis grouped omTLR1 with other fish TLR1 genes on
      a separate branch from the avian TLR1 and mammalian TLR1, 6 and 10. omTLR1
      expression levels in rainbow trout anterior kidney leukocytes were not affected
      by the human TLR2/6 and TLR2/1 agonists diacylated lipoprotein (Pam(2)CSK(4)) and
      triacylated lipoprotein (Pam(3)CSK(4)). However, due to the lack of TLR6 and 10
      genes in teleost genomes and up-regulation of TLR1 mRNA in response to LPS and
      bacterial infection in other fish species we hypothesize an important role for
      omTLR1 in anti-microbial immunity. Therefore, the identification of a TLR2
      ortholog in rainbow trout and the development of assays to measure ligand binding
      and downstream signaling are critical for future elucidation of omTLR1 functions.

PMID- 20153435
TI  - Antioxidant enzymes from the crab Scylla paramamosain: gene cloning and
      gene/protein expression profiles against LPS challenge.
AB  - Recent studies revealed that antioxidant enzymes play important roles in
      antioxidant responses caused by metabolic process or pathogen invasion. Catalase
      is one of these key enzymes which has been characterized and highly conserved
      from invertebrates to vertebrates. In the present study, a full-length cDNA
      sequence of catalase was cloned from the hemocyte suppression subtractive
      hybridization library of the crab Scylla paramamosain. The Sp-catalase (Sp-CAT)
      cDNA sequence contained 2551bp with an open reading frame of 1551bp encoding 517
      amino acid residues. The conserved catalytic active residues His-71, Asn-144 and
      Tyr-354 were predicted in the amino acid sequence of Sp-CAT. The deduced Sp-CAT
      protein had a calculated molecular mass of 59 kDa with an estimated isoelectric
      point of 6.4. Multiple alignment analysis revealed that the deduced amino acid
      sequence of Sp-CAT shared high identity (75.4%) with those of other species. The
      Sp-CAT mRNA transcripts were demonstrated in multiple tissues of normal S.
      paramamosain. After LPS challenge, the expression level of Sp-CAT gene was
      increased significantly in hemocyte at 3 and 6 h, and in hepatopancreas at 6 h,
      respectively, determined by quantitative real-time PCR. Furthermore, the
      activities of CAT and SOD were also measured in different tissues and serum after
      LPS challenge. The CAT activity was significantly increased at 3, 6, 24 and 48 h
      in hemocyte lysate, at 3 h in serum, and at 24 and 48 h in hepatopancreas after
      LPS challenge. In addition, the SOD activity was significantly induced at 3 and 6
      h in hemocyte lysate, 3 and 12 h in serum, 12 and 48 h in hepatopancreas post LPS
      stimulation, indicating a tissue and time-dependent antioxidant response in the
      crab. Taken together, these data demonstrated that a strong antioxidant response
      occurred in the LPS-challenged crab, which might be involved in the protection of
      host against microbial infections.

PMID- 20153436
TI  - Cloning of an orange-spotted grouper Epinephelus coioides heat shock protein 90AB
      (HSP90AB) and characterization of its expression in response to nodavirus.
AB  - The heat shock proteins (HSPs) family which consists of HSP90, HSP70, and low
      molecular mass HSPs are involved in chaperone activity. Here, we report the
      cloning and characterization of HSP90AB gene from orange-spotted grouper,
      Epinephelus coioides. The full-length of grouper HSP90AB was 727 amino acids and
      possessed an ATPase domain as well as an evolutionarily conserved molecular
      chaperone. The HSP90AB-green fluorescent protein fusion protein was evenly
      distributed in the cytoplasm. Immunohistochemistry (IHC) and real-time polymerase
      chain reaction (PCR) analyses indicated that the expression of grouper HSP90AB
      was marginally increased following nodavirus infection. Grouper E. coioides that
      received HSP90 inhibitor geldanamycin (GA) showed an increase in HSP90AB
      expression and growth of nodavirus supporting nodavirus replication.

PMID- 20153437
TI  - Using an improved Tol2 transposon system to produce transgenic zebrafish with
      epinecidin-1 which enhanced resistance to bacterial infection.
AB  - In order to advance the application of antimicrobial peptides in aquaculture,
      transgenic zebrafish expressing the antimicrobial peptide, epinecidin-1, were
      developed and are reported on here. First, we cloned the zebrafish mylz2 promoter
      for this purpose. To characterize the activity of the mylz2 promoter, various
      fragments of it were analyzed using a firefly luciferase transient expression
      assay, in which maximum promoter activity was found with a 2.5-kb fragment. In
      addition, the 2.5-kb fragment also expressed considerable red fluorescent
      proteins in skeletal muscles of transgenic zebrafish. Second, in order to improve
      the translation efficiency of the Tol2 transposase, we constructed untranslated
      regions (UTRs) of zebrafish ba1 globin flanked by a transposase. A transient
      embryonic excision assay (TEEA) and in vivo fluorescent observations showed high
      transposition efficiency during embryonic development. After optimization of the
      promoter and transgene efficiencies, transgenic zebrafish with the Epi-1/DsRed
      plasmid (pTLR-m2.5 K-K.Epinecidin-1/DsRed vector) were developed, and expressions
      of Epi-1/DsRed in muscles and blood were demonstrated by immunohistochemical
      staining techniques. Moreover, we also found that the Epi-1/DsRed gene was
      efficiently and significantly expressed in vivo against Vibrio vulnificus and
      Streptococcus agalactiae after injecting the bacteria and determining bacterial
      counts. A gene expression study using real-time RT-PCR revealed that Epi-1/DsRed
      itself induced endogenous MyD88 expression in vivo. After Epi-1/DsRed transgenic
      zebrafish were infected with V. vulnificus 204, interleukin (IL)-10, IL-22, IL
      26, lysozyme, toll-like receptor (TLR)1, TLR3, TLR4a, MyD88, and nuclear factor
      (NF)-kappaB activating protein-like were upregulated, but IL-1beta and tumor
      necrosis factor-alpha were downregulated at 12h post-infection; IL-21, complement
      component c3b, and NF-kappaB activating protein-like were downregulated, but
      MyD88 was upregulated at 24h post-infection. These results suggest that using
      epinecidin-1 as a transgene in zebrafish can effectively inhibit bacterial growth
      for up to 24h after infection.

PMID- 20153438
TI  - Opioid and non-opioid receptor-mediated immunoregulatory role of leucine
      enkephalin in teleost Channa punctatus.
AB  - Leucine-enkephalin (Leu-enk) is an endogenous opioid peptide and highly conserved
      throughout the vertebrates. Despite its conserved nature, the immunoregulatory
      property of Leu-enk is explored only in mammals. The present study describes the
      immunomodulatory role of Leu-enk in a lower vertebrate, spotted murrel Channa
      punctatus. Leu-enk increased the percentage phagocytosis and phagocytic index,
      though its stimulatory effect on phagocytosis markedly decreased at
      concentrations higher than 10(-9) M. Moreover, it had bell-shaped stimulatory
      effect also on the superoxide production by phagocytes. On the other hand, Leu
      enk showed bimodal effects on nitrite release. The lower concentrations of Leu
      enk produced inhibitory effect, while higher concentrations had stimulatory
      effect on nitrite release. Interestingly, the Leu-enk-induced increase in nitrite
      release was unaltered by non-selective opioid receptor antagonist though the same
      completely antagonized the inhibitory effect of Leu-enk on nitrite release and
      the stimulatory effect on phagocytosis and superoxide production. This suggests
      that the stimulatory effect of Leu-enk on nitrite production is mediated by the
      non-opioid receptor. Further, delta-opioid receptor was precisely seen involved
      in mediating the stimulatory effect of Leu-enk on phagocytosis and superoxide
      production, or inhibitory effect on nitrite release. It can be concluded that Leu
      enk regulates the innate immune response of splenic phagocytes acting via both
      opioid and non-opioid receptor in the fish C. punctatus.

PMID- 20153440
TI  - Antimicrobial activity in the tissues of Atlantic cod (Gadus morhua L.).
AB  - Antimicrobial peptides (AMP) are important components of the innate immune system
      in metazoans. They have been studied widely in several fishes, but little is
      known about these defence factors in Atlantic cod, which is thought to have a
      less sophisticated adaptive immune system compared to other teleosts. The aim of
      the present study was to screen for potential AMPs in various tissues of Atlantic
      cod and to examine their spectra of activity. Acidic crude extracts were prepared
      from thirteen tissues (i.e. mucus, gills, skin, intestine, rectum, head kidney,
      spleen, blood, gall bladder, liver, ovary, muscle and peritoneal wall). Following
      partial purification by solid-phase extraction, 78 fractions were obtained and
      these were assayed for antimicrobial activity using a two-layer radial diffusion
      assay. Some of the fractions prepared from several tissues examined had potent
      activity against the test bacteria. In general, acetonitrile rich fractions
      displayed higher antibacterial activity than the aqueous ones. The most potent
      fractions were obtained from the gall bladder and they exhibited potent
      antimicrobial activity against 8 of the 9 test bacteria, including the cod
      pathogen Vibrio anguillarum. Antibacterial activity was completely eliminated or
      reduced upon treatment with proteinase K in most fractions. Protein profiles
      obtained by SDS-PAGE and two-dimensional gel electrophoresis showed that
      antimicrobial activity of the partially purified tissue extracts might be due to
      cationic, low molecular weight peptides.

PMID- 20153439
TI  - Effect of endocrine disrupting chemicals on the transcription of genes related to
      the innate immune system in the early developmental stage of zebrafish (Danio
      rerio).
AB  - Health concerns regarding the potential interference of endocrine disrupting
      chemicals (EDCs) in the immune system of wildlife and humans have increased in
      recent years. However, the effects of EDCs in aquatic systems on the immune
      system of fish species has only received limited attention. In the present study,
      we found that the mRNA levels of TNFalpha, IFN, IL-1beta, IL-8, CXCL-Clc, and CC
      chemokine, which are closely related to the innate immune system, were affected
      in newly hatched zebrafish when exposed to EDCs, such as 17beta-estradiol,
      17alpha-ethynyestradiol, permethrin, atrazine and nonylphenol at various
      concentrations (0.1, 0.5, 2.5 and 12.5 microg/l) for three days during the embryo
      stage. However, the different EDCs displayed different potentials to change
      innate immune-related gene transcription. Among the selected chemicals,
      permethrin (PM) and 17beta-estradiol (E2) (12.5 microg/l) significantly increased
      the mRNA levels of many cytokines, exhibiting their most prominent impacts on the
      innate immune system of zebrafish. In addition, it was found that the mixture of
      the above five chemicals (2.5 microg/l each) had a greater effect on innate
      immune system-related gene transcription in zebrafish than equal amounts of the
      single compound. Moreover, the genes (such as Bcl2, Ucp2 and iNOS) relating to
      reactive oxygen species (ROS) and nitrogen reactive free radical production were
      also influenced by some EDCs and their mixture. We suggest that heavy oxidative
      stress and the balance of nitric oxide (NO) production lead to death of immune
      cells. These results may provide an explanation of the possible mode how EDCs
      influence the innate immune system in zebrafish. Taken together, the results
      obtained in the present study clearly demonstrate that EDCs and their mixtures in
      aquatic systems will greatly influence the immune system in fish, suggesting that
      the effects of EDCs on fish should be associated with immune toxicity.

PMID- 20153441
TI  - White shrimp Litopenaeus vannamei that received the hot-water extract of
      Gracilaria tenuistipitata showed protective innate immunity and up-regulation of
      gene expressions after low-salinity stress.
AB  - White shrimp Litopenaeus vannamei which had been immersed in seawater (35 per
      thousand) containing the hot-water extract of Gracilaria tenuistipitata at 0
      (control), 200, 400, and 600 mg L(-1) for 3 h, were subjected to a salinity
      transfer to 25 per thousand, and the immune parameters including hyaline cells
      (HCs), granular cells (GCs, including semi-granular cells), total haemocyte count
      (THC), phenoloxidase (PO) activity, respiratory burst (RB), superoxide dismutase
      (SOD) activity, haemolymph protein concentration, and transcripts of the
      lipopolysaccharide- and beta-glucan-binding protein (LGBP), peroxinectin (PX),
      and alpha2-macroglobulin (alpha2-M) were examined 6-96 h post-transfer. Shrimp
      with no exposure to the hot-water extract and no salinity transfer served as the
      background control. Results indicated that HCs, GCs, THC, PO activity, RB, SOD
      activity, and haemolymph protein concentration of shrimp immersed in 600 mg L(-1)
      extract were significantly higher than those of control shrimp at 6-12 h post
      transfer. Results also indicated that these parameters of shrimp immersed in 600
      mg L(-1) extract had returned to the background values at 12, 6, 12, 6, 12, 24,
      and 24 h post-transfer with significant transcripts of LGBP, PX, and alpha2-M at
      12 h, whereas these immune parameters in control shrimp had returned to the
      original values at 96 h post-transfer. It was therefore concluded that the innate
      immunity of L. vannamei which had been immersed in seawater containing the hot
      water extract of G. tenuistipitata exhibited a protective effect against low
      salinity stress as evidenced by increases in LGBP, PX, and alpha2-M transcripts,
      and earlier recovery of immune parameters.

PMID- 20153442
TI  - Optimising in vivo pharmacology studies--Practical PKPD considerations.
AB  - INTRODUCTION: It has become apparent in recent years that there is a need for a
      substantial improvement in the processes used to clarify the inter-relationships
      between a compound's pharmacokinetic (PK) characteristics, its target actions and
      its safety profile. This is particularly challenging because most of the
      techniques currently used to obtain meaningful data involve low efficiency animal
      studies. To maximize the value of such in vivo studies, time and resources need
      to be better utilized. One way of making major advances is to adopt an
      integrative approach to designing and analysing in vivo pharmacodynamic (PD)
      studies. In this paper we address experimental design issues related to
      maximizing the information content about target engagement. Refined integration
      of PK and PD (known as 'quantitative pharmacology' or a PKPD approach) is
      advocated, enabling clarification of the interdependence of a drug's
      pharmacological properties on its target physiological system(s) and its systemic
      exposure characteristics. METHODS: Several in vivo pharmacological Case Studies
      are presented which are used to illustrate the discussion of issues of
      experimental design. The impact of rate, extent and mode of administration is
      discussed from a pharmacological viewpoint, and we examine the consequences of
      temporal differences between concentration and response from the perspective of
      experimental design. We also consider the importance of differences in plasma
      protein binding (PPB) on our ability to assess a pharmacodynamic property or
      safety margin, and examine the usefulness of measuring ex vivo PPB. Finally, we
      outline the value of implementing a clearly pre-determined, integrated work flow
      to generate, validate and maximize in vivo PKPD or preclinical disease model
      data, and summarize the key issues of experimental design. RESULTS AND
      DISCUSSION: Quantitative pharmacological reasoning focuses on concentration
      response and response-time relationships with special emphasis on the impact of
      drugs on disease (Levy, 1993) and this perspective was written to raise awareness
      among in vivo scientists as to why PKPD integration is essential in their
      studies.

PMID- 20153443
TI  - The action potential and comparative pharmacology of stem cell-derived human
      cardiomyocytes.
AB  - INTRODUCTION: The cardiac action potential (CAP) of stem cell-derived human
      cardiomyocytes (SC-hCMs) is potentially the most powerful preclinical biomarker
      for cardiac safety and efficacy in humans. Our experiments tested this hypothesis
      by examining the CAP and relevant pharmacology of these cells. METHODS: The
      electrophysiological and pharmacological profiles of SC-hCMs were compared to
      rabbit and canine Purkinje fibers (PFs). Ventricular SC-hCMs provided the
      dominant electrophysiological phenotype (approximately 82%) in a population of
      ventricular, atrial and nodal cardiomyocytes (CMs). The effects of reference
      compounds were measured in SC-hCMs using perforated patch, current clamp
      recording. Selective inhibitors of I(Kr), I(Ks), I(Ca,L), and I(Na), and
      norepinephrine (NE), were tested on SC-hCM action potentials (APs). RESULTS: AP
      prolongation was observed upon exposure to hERG channel blockers (terfenadine,
      quinidine, cisapride, sotalol, E-4031 and verapamil), with significantly shorter
      latencies than in PF assays. For the torsadogenic compounds, terfenadine and
      quinidine, SC-hCM AP prolongation occurred at significantly lower concentrations
      than in canine or rabbit PF APs. Moreover, the I(Ks) blocker chromanol 293B
      prolonged APs from SC-hCMs, whereas both rabbit and canine PF assays are
      insensitive to I(Ks) blockers in the absence of adrenergic preconditioning. Early
      afterdepolarizations (EADs) were induced by 100 nM E-4031 and 100 nM cisapride in
      the SC-hCM assay, but not in the canine or rabbit PF assay. Selective inhibition
      of I(Na) and I(Ca,L) slowed V(max) and shortened AP duration, respectively. NE
      prolonged the AP duration of SC-hCMs. DISCUSSION: The CAP of SC-hCMs has been
      validated as a powerful preclinical biomarker for cardiac safety and efficacy. In
      addition to its human nature, the SC-hCM AP assay removes diffusion delays,
      reduces test compound consumption, demonstrates an overall pharmacological
      sensitivity that is greater than conventional rabbit or canine PF assays, and
      accurately predicts cardiac risk of known torsadogenic compounds.

PMID- 20153444
TI  - Load carrying during locomotion in the barnacle goose (Branta leucopsis): the
      effect of load placement and size.
AB  - Load carrying has been used to study the energetics and mechanics of locomotion
      in a range of taxa. Here we investigated the energetic and kinematic effects of
      trunk and limb loading in walking barnacle geese (Branta leucopsis). A directly
      proportional relationship between increasing back-load mass and metabolic rate
      was established, indicating that the barnacle goose can carry back loads (up to
      20% of body mass) more economically than the majority of mammals. The increased
      cost of supporting and propelling the body during locomotion is likely to account
      for a major proportion of the extra metabolic cost. Sternal loads up to 15% of
      body mass were approximately twice as expensive to carry as back loads. Given the
      key role in dorso-ventral movement of the sternum during respiration we suggest
      that moving this extra mass may account for the elevated metabolic rate. Loading
      the distal limb with 5% extra mass incurred the greatest proportional rise in
      metabolism, and also caused increases in stride length, swing duration and stride
      frequency during locomotion. The increased work required to move the loaded limb
      may explain the high cost of walking.

PMID- 20153445
TI  - Induction of cell death on Plasmodium falciparum asexual blood stages by Solanum
      nudum steroids.
AB  - Solanum nudum Dunal (Solanaceae) is a plant used in traditional medicine in
      Colombian Pacific Coast, from which five steroids denominated SNs have been
      isolated. The SNs compounds have antiplasmodial activity against asexual blood
      stages of Plasmodium falciparum strain 7G8 with an IC(50) between 20-87microM.
      However, their mode of action is unknown. Steroids regulate important cellular
      functions including cell growth, differentiation and death. Thus, the aim of this
      work was to determine the effects of S. nudum compounds on P. falciparum asexual
      blood stages and their association with cell death. We found that trophozoite and
      schizont stages were the most sensitive to SNs. By Giemsa-stained smears,
      induction of crisis forms was observed. Transmission electron microscopy of
      treated parasites showed morphological abnormalities such as a cytoplasm rich in
      vesicles and myelinic figures. The Mitochondria presented no morphological
      alterations and the nuclei showed no abnormal chromatin condensation. By the use
      of S. nudum compounds, cell death in P. falciparum was evident by a decrease in
      mitochondrial membrane potential, DNA fragmentation and cytoplasmic
      acidification. The asexual blood stages of P. falciparum showed some apoptotic
      like and autophagic-like cell death characteristics induced by SNs treatment.

PMID- 20153446
TI  - A novel DEAD box helicase Has1p from Plasmodium falciparum: N-terminal is
      essential for activity.
AB  - Helicases catalyze the opening of nucleic acid duplexes and are implicated in
      many nucleic acid metabolic cellular processes that require single stranded DNA
      or reorganization of RNA structure. Previously we have reported that Plasmodium
      falciparum genome contains a number of DEAD box helicases. In the present study
      we report the cloning, expression and characterization of one of the novel
      members of DEAD box family from P. falciparum. Our results indicate that it is a
      homologue of Has1p from yeast and it contains DNA and RNA unwinding, nucleic acid
      dependent ATPase and RNA binding activities. This enzyme can utilize all the
      nucleosidetriphosphates (NTPs) and deoxy nucleosidetriphosphates (dNTPs) for its
      unwinding activity. Using a truncated derivative of this protein we further
      report that the N-terminal region of the protein is essentially required for its
      activity. These studies suggest that besides the conserved helicase domain the
      highly variable N-terminal region also contributes in the activity of the
      protein.

PMID- 20153448
TI  - Early repolarization and ventricular fibrillation: vagally familiar?

PMID- 20153450
TI  - Understanding ethical issues, ICD, and DNR orders: an obstacle to imminent death?

PMID- 20153447
TI  - Altered lipid A structures and polymyxin hypersensitivity of Rhizobium etli
      mutants lacking the LpxE and LpxF phosphatases.
AB  - The lipid A of Rhizobium etli, a nitrogen-fixing plant endosymbiont, displays
      significant structural differences when compared to that of Escherichia coli. An
      especially striking feature of R. etli lipid A is that it lacks both the 1- and
      4'-phosphate groups. The 4'-phosphate moiety of the distal glucosamine unit is
      replaced with a galacturonic acid residue. The dephosphorylated proximal unit is
      present as a mixture of the glucosamine hemiacetal and an oxidized 2
      aminogluconate derivative. Distinct lipid A phosphatases directed to the 1 or the
      4'-positions have been identified previously in extracts of R. etli and Rhizobium
      leguminosarum. The corresponding structural genes, lpxE and lpxF, respectively,
      have also been identified. Here, we describe the isolation and characterization
      of R. etli deletion mutants in each of these phosphatase genes and the
      construction of a double phosphatase mutant. Mass spectrometry confirmed that the
      mutant strains completely lacked the wild-type lipid A species and accumulated
      the expected phosphate-containing derivatives. Moreover, radiochemical analysis
      revealed that phosphatase activity was absent in membranes prepared from the
      mutants. Our results indicate that LpxE and LpxF are solely responsible for
      selectively dephosphorylating the lipid A molecules of R. etli. All the mutant
      strains showed an increased sensitivity to polymyxin relative to the wild-type.
      However, despite the presence of altered lipid A species containing one or both
      phosphate groups, all the phosphatase mutants formed nitrogen-fixing nodules on
      Phaseolus vulgaris. Therefore, the dephosphorylation of lipid A molecules in R.
      etli is not required for nodulation but may instead play a role in protecting the
      bacteria from cationic antimicrobial peptides or other immune responses of
      plants.

PMID- 20153452
TI  - A combined metabolic/polymerization kinetic model on the microbial production of
      poly(3-hydroxybutyrate).
AB  - In the present work, an integrated dynamic metabolic/polymerization kinetic model
      is developed for the prediction of the intracellular accumulation profile and the
      molecular weight distribution of poly(3-hydroxybutyrate) (P(3HB) or PHB) produced
      in microbial cultures. The model integrates two different length/time scales by
      combining a polymerization kinetic model with a metabolic one. The bridging point
      between the two models is the concentration of the monomer unit (i.e. 3
      hydroxybutyryl-CoA) produced during the central aerobic carbon metabolism. The
      predictive capabilities of the proposed model are assessed by the comparison of
      the calculated biopolymer concentration and number average molecular weight with
      available experimental data obtained from batch and fed-batch cultures of
      Alcaligenes eutrophus and Alcaligenes latus. The accuracy of the proposed model
      was found to be satisfactory, setting this model a valuable tool for the design
      of the process operating profile for the production of different polymer grades
      with desired molecular properties.

PMID- 20153451
TI  - DmsD, a Tat system specific chaperone, interacts with other general chaperones
      and proteins involved in the molybdenum cofactor biosynthesis.
AB  - Many bacterial oxidoreductases depend on the Tat translocase for correct cell
      localization. Substrates for the Tat translocase possess twin-arginine leaders.
      System specific chaperones or redox enzyme maturation proteins (REMPs) are a
      group of proteins implicated in oxidoreductase maturation. DmsD is a REMP
      discovered in Escherichia coli, which interacts with the twin-arginine leader
      sequence of DmsA, the catalytic subunit of DMSO reductase. In this study, we
      identified several potential interacting partners of DmsD by using several in
      vitro protein-protein interaction screening approaches, including affinity
      chromatography, co-precipitation, and cross-linking. Candidate hits from these in
      vitro findings were analyzed by in vivo methods of bacterial two-hybrid (BACTH)
      and bimolecular fluorescence complementation (BiFC). From these data, DmsD was
      confirmed to interact with the general molecular chaperones DnaK, DnaJ, GrpE,
      GroEL, Tig and Ef-Tu. In addition, DmsD was also found to interact with proteins
      involved in the molybdenum cofactor biosynthesis pathway. Our data suggests that
      DmsD may play a role as a "node" in escorting its substrate through a cascade of
      chaperone assisted protein-folding maturation events.

PMID- 20153454
TI  - Characterisation of phase transition in adsorbed monolayers at the air/water
      interface.
AB  - Recent work has provided experimental and theoretical evidence that a first order
      fluid/condensed (LE/LC) phase transition can occur in adsorbed monolayers of
      amphiphiles and surfactants which are dissolved in aqueous solution. Similar to
      Langmuir monolayers, also in the case of adsorbed monolayers, the existence of a
      G/LE phase transition, as assumed by several authors, is a matter of question.
      Representative studies, at first performed with a tailored amphiphile and later
      with numerous other amphiphiles, also with n-dodecanol, provide insight into the
      main characteristics of the adsorbed monolayer during the adsorption kinetics.
      The general conditions necessary for the formation of a two-phase coexistence in
      adsorbed monolayers can be optimally studied using dynamic surface pressure
      measurements, Brewster angle microscopy (BAM) and synchrotron X-ray diffraction
      at grazing incidence (GIXD). A characteristic break point in the time dependence
      of the adsorption kinetics curves indicates the phase transition which is largely
      affected by the concentration of the amphiphile in the aqueous solution and on
      the temperature. Formation and growth of condensed phase domains after the phase
      transition point are visualised by BAM. As demonstrated by a tailored amphiphile,
      various types of morphological textures of the condensed phase can occur in
      different temperature regions. Lattice structure and tilt angle of the alkyl
      chains in the condensed phase of the adsorbed monolayer are determined using
      GIXD. The main growth directions of the condensed phase textures are correlated
      with the two-dimensional lattice structure. The results, obtained for the
      characteristics of the condensed phase after a first order main transition, are
      supported by experimental bridging to the Langmuir monolayers. Phase transition
      of adsorbing trace impurities in model surfactants can strongly affect the
      characteristics of the main component. Dodecanol present as minor component in
      aqueous sodium dodecylsulfate solution dominate largely the fundamental features
      of the adsorbed monolayer of the mixed dodecanol/SDS solutions at adsorption
      equilibrium. A theoretical concept on the basis of the quasi-chemical model and
      assumption of the entropy non-ideality has been developed which can well describe
      the experimental results of the diffusion kinetics of surfactant adsorption from
      solutions. The model regards the phase behaviour of adsorbed monolayers on the
      basis of the experimental results explicitly supported by the first order
      fluid/condensed phase transition and theoretical models assuming bimodal
      distribution between large aggregates (domains) and monomers and/or very small
      aggregates. Another simple theoretical model for the description of the
      coadsorption of surfactant mixtures, based on the additivity of the contributions
      brought by the solution components into the surface pressure is shown to be in
      qualitative agreement with the experimental data of mixed dodecanol/SDS
      solutions. The theoretical results corroborate the fact that the formed condensed
      phase (large aggregates) in the mixed monolayer consists mainly of dodecanol.

PMID- 20153453
TI  - Sp1 and Sp3 regulate transcription of the chicken GAS41 gene.
AB  - The 5'-flanking region of the chicken glioma-amplified sequence (GAS) 41 gene is
      close to the 3' end of the lysozyme gene and contains no typical TATA box, but
      several GC boxes. In this study, we have localized the GAS 41 promoter to this
      narrow region. Electrophoretic mobility shift assays and chromatin
      immunoprecipitation analyses revealed that Sp1 and Sp3 bind to this promoter.
      Mapping by a technique of indirect end labeling demonstrated that the Sp1-binding
      sites contained in this region exactly co-map with two previously identified
      DNase I hypersensitive (HS) sites, which suggests the important role of Sp1
      binding in maintaining an open chromatin structure of the GAS41 promoter. We
      further found that Sp1 and Sp3 strongly activate CAT expression controlled by the
      putative GAS41 promoter in Drosophila Schneider S2 cells and that deletion of the
      Sp1 sites resulted in a loss of promoter activity in chicken HD11 cells. The
      results indicate that transcription factors of the Sp family play an important
      role in the transcriptional regulation of the chicken GAS41 gene.

PMID- 20153455
TI  - Descriptive analyses of Turner syndrome: 49 cases in Tunisia.
AB  - Turner syndrome is linked to the absence or abnormality of one of the X
      chromosome leading to haplo-insufficiency of genes involved in the development
      and maintenance of the ovarian stock in women. We report the results of a 21-year
      retrospective study, conducted in 49 patients with Turner syndrome. The purpose
      of this study was to establish the clinical, hormonal, cytogenetic and evolutive
      pattern of a Tunisian population with Turner syndrome and to search for
      correlations between genotype and phenotype. The average age of our patients at
      diagnosis was 14 years (1 day-42 years). Twenty-four percent of them were
      diagnosed in adulthood (greater than or equal to 20 years). Turner syndrome was
      diagnosed later in the case of mosaicism (P=0.001). Short stature was present in
      85% of cases; it was more frequent among the youngest and monosomics. The
      dysmorphic syndrome was observed in 85% of cases; it was significantly more
      frequent in monosomics (P=0.003). Delayed puberty was present in 62.4% of cases,
      it was almost constant in monosomics (P=0.05). The loss of ovarian function was
      more severe in case of monosomia compared to other forms (P=0.04). Our results
      report a high frequency of autoimmune diseases (18/46 cases) including
      dysthyroidism (eight cases). Hepato biliary affections were more frequent in
      mosaicism compared to monosomy. The average final height was greater even in
      mosaicism estimated at 150.5 cm compared to 141 cm in monosomics and 138.8 cm in
      mosaics with abnormal structures.

PMID- 20153456
TI  - Macroergonomics and patient safety: the impact of levels on theory, measurement,
      analysis and intervention in patient safety research.
AB  - The study and practice of patient safety has seen a surge over the last 10 years.
      New resident training and staffing policies, health information technologies,
      error reporting systems, team models of care, training methods, patient
      involvement, information handoff strategies, just cultures, and many other
      interventions have been mandated or attempted to improve the safety of patient
      care. While some of these interventions focus on individual providers and others
      focus on organization-level changes, little, if any, patient safety research has
      purposefully sought to understand how variables at different levels, such as the
      provider level or organization level, interact to impact patient safety outcomes
      such as errors, adverse drug events, or patient harm. Looking at relationships
      across levels is important because adverse events might be related to variables
      at different levels; consider that adverse events may be nested within patients,
      patients nested within nurses and physicians, nurses and physicians nested within
      shifts, shifts nested within hospital units, and so forth. Because these nested
      levels exist, they may exert as yet untested influence on the levels below. In
      this paper the impact of levels on theory, measurement, analysis and intervention
      in patient safety research is discussed.

PMID- 20153457
TI  - Designing packaging to support the safe use of medicines at home.
AB  - In the light of a number of serious incidents in the UK resulting from accidental
      overdoses of methotrexate, this study investigated how the design of methotrexate
      packaging can influence patient safety, and aimed to collect evidence to provide
      a basis for the development of new concepts for revised designs by the
      pharmaceutical industry. The research found that patients using methotrexate
      experience a number of difficulties in using their medicines packaging, and as a
      result, resourcefully adopt a variety of "coping strategies" which may increase
      the risk of dosing errors. By investigating both the practice of methotrexate
      users, and the design of the system that supports methotrexate use, additional
      problems were observed across the healthcare system, meaning that the function of
      medicines packaging in ensuring safety may be even more critical than first
      suspected. As a result of this research the National Patient Safety Agency
      responded with a UK-wide programme of work to improve safety for patients, and
      continues to work with the pharmaceutical industry to develop more user-friendly
      packaging and labelling.

PMID- 20153458
TI  - Effects of fire fighter protective ensembles on mobility and performance.
AB  - Many studies have shown that fire fighter turnout gear and equipment may restrict
      mobility. The restriction of movement is usually due to a decrease in range of
      motion (ROM). It is important to know how much the decrease in ROM affects
      performance. The aim of this study was to determine the effects of fire fighter
      protective ensembles on mobility and performance by measuring static and dynamic
      range of motion (ROM) and job-related tasks. Eight healthy adults (5 males, 3
      females), aged 20-40 years, participated in this study. The study consisted of
      measuring a battery of motions and fire fighter specific tasks while wearing a
      standard fire fighter ensemble (SE) or regular light clothing (baseline or BL).
      Several BL ROM tests were significantly (p < 0.05) different from the SE test,
      including a decrease in shoulder flexion, cervical rotation and flexion, trunk
      lateral flexion, and stand and reach. There was a significant decrease in time
      from SE to baseline performing the one-arm search task and object lift. These
      overall findings support the need for a comprehensive ergonomic evaluation of
      protective clothing systems to ascertain human factors issues. The development of
      a Standard Ergonomics Test Practice for further use in laboratories that conduct
      personal protective systems evaluations using human test subjects is recommended.

PMID- 20153459
TI  - An experimental manipulation of responsibility in children: a test of the
      inflated responsibility model of obsessive-compulsive disorder.
AB  - The objective of this study was to investigate whether Salkovskis (1985) inflated
      responsibility model of obsessive-compulsive disorder (OCD) applied to children.
      In an experimental design, 81 children aged 9-12 years were randomly allocated to
      three conditions: an inflated responsibility group, a moderate responsibility
      group, and a reduced responsibility group. In all groups children were asked to
      sort sweets according to whether or not they contained nuts. At baseline the
      groups did not differ on children's self reported anxiety, depression, obsessive
      compulsive symptoms or on inflated responsibility beliefs. The experimental
      manipulation successfully changed children's perceptions of responsibility.
      During the sorting task time taken to complete the task, checking behaviours,
      hesitations, and anxiety were recorded. There was a significant effect of
      responsibility level on the behavioural variables of time taken, hesitations and
      check; as perceived responsibility increased children took longer to complete the
      task and checked and hesitated more often. There was no between-group difference
      in children's self reported state anxiety. The results offer preliminary support
      for the link between inflated responsibility and increased checking behaviours in
      children and add to the small but growing literature suggesting that cognitive
      models of OCD may apply to children.

PMID- 20153460
TI  - Predictors of outcome in residential cognitive and interpersonal treatment for
      social phobia: do cognitive and social dysfunction moderate treatment outcome?
AB  - BACKGROUND: The predictors of residential cognitive (RCT) and residential
      interpersonal Treatment (RIPT) for social phobia were explored. (1) Sotsky et al.
      (1991) found differential effects of CT and IPT for depression, suggesting that
      the level of cognitive or social dysfunction predicted differential outcome. We
      examined whether an analogous effect could be demonstrated in 10 weeks of
      residential treatment of 80 social phobia subjects. (2) We also included
      expectations, age of onset, severity of illness, concurrent anxiety, mood,
      avoidant personality disorder, and body dysmorphic disorder as predictors in this
      exploratory study. METHOD: Main outcome was the social phobia subscale of Social
      Phobia and Anxiety Inventory (SPAI SP). DSM-IV axis I and II interviews were
      completed. RESULTS: (1) Sotsky et al. (1991) findings were not reproduced.
      However, RIPT subjects with poor general functioning were less improved following
      treatment. Subjects with concurrent agoraphobia responded better with RCT than
      subjects without agoraphobia. (2) Age of onset and expectations were the most
      powerful predictors of post treatment outcome. CONCLUSION: Some patient
      characteristics appear to impact outcome with RIPT and RCT differentially. The
      findings are discussed.

PMID- 20153461
TI  - [Primary hyperhidrosis. Current status of surgical treatment].
AB  - Primary hyperhidrosis-PH is an excessive sweating without known etiology. The PH
      is more frequent in women and in palms, soles and axillae. Medical treatment is
      not effective. The objective of the surgery is to remove or to disconnect
      sympathetic ganglia T2 (craniofacial PH or facial blushing), T3 (palmar PH) and
      T3-T4 (axillary PH). The surgical techniques are mainly resection/transection,
      ablation with electrocoagulation, sympathetic block by clipping and
      radiofrequency. Anhidrosis is achieved in 95% of the patients. The overall rate
      of complications is less than 5% and these are minor complications. The most
      important unwanted effect is reflex sweating, presented in 48% of the patients.
      Reflex sweating is more frequent in back, thorax and abdomen and it appears
      independently of the surgical technique. Ninety percent of the patients are very
      satisfied after surgery. Nowadays, thoracic sympathetic surgery is the gold
      standard for primary hyperhidrosis.

PMID- 20153462
TI  - 3-Year-olds' comprehension, production, and generalization of Sesotho passives.
AB  - Researchers have long been puzzled by the challenge English passive constructions
      present for language learners, with adult-like comprehension and production
      emerging only around the age of 5. It has therefore been of significant interest
      that researchers of other languages, including the Bantu language Sesotho, have
      reported acquisition of the passive by the age of 3 (Demuth, 1989). Such reports
      have typically been based on spontaneous production data, calling for further
      investigation. This study carried out a series of experiments with Sesotho
      speaking 3-year-olds, testing their ability to comprehend the passive, produce
      the passive, and generalize novel verbs to passive frames. The results showed
      that passive comprehension was good, with no effect of actional/non-actional verb
      type. Elicited production of the passive was also good, with no difference
      between adversive and non-adversive verbs. Finally, all participants made both
      active and passive generalizations to novel verbs. These findings provide strong
      evidence that Sesotho-speaking 3-year-olds have robust, abstract knowledge of
      passive syntax. The paper concludes with a discussion of the factors that
      contribute to the early learning of the Sesotho passive, why acquisition of the
      passive may be delayed in English, and the implications for understanding
      grammatical development more generally.

PMID- 20153463
TI  - Impaired capacity for autonoetic reliving during autobiographical event recall in
      mild Alzheimer's disease.
AB  - The capacity to mentally travel back in time and relive past events via
      autonoetic consciousness has been shown to be compromised even in the early
      stages of Alzheimer's disease (AD). To further understand the unravelling of the
      recollective experience in pathological ageing, we investigated autobiographical
      memory (ABM) using the Episodic Autobiographical Memory Interview (EAMI) in
      thirty middle-aged and thirty healthy elderly controls, and twenty patients with
      mild AD. Of key interest was the recall of contextual details and the behavioural
      markers predictive of autonoetic reliving. AD patients exhibited significant
      difficulties in recalling contextual details across all life epochs on the EAMI
      manifesting in a negative temporal gradient from the Early Adulthood epoch
      onwards. Overall there was a low incidence of autonoetic consciousness during ABM
      recall across all participant groups and life epochs when compared with previous
      studies. AD patients showed a compromised capacity to mentally relive past
      memories (AD<healthy elderly<middle-aged controls), across all life epochs on the
      EAMI. AD patients tended to recall past events as semanticised accounts divested
      of rich sensory-perceptual imagery. The impoverished capacity to generate
      egocentric or self-referential imagery resulted in the production of fragmented
      and depersonalised accounts of formerly evocative events and likely stems from
      medial temporal and frontal pathology exhibited from early stages of the disease.

PMID- 20153464
TI  - Cortex covers 2008.

PMID- 20153465
TI  - [The importance of tricuspid murmur].

PMID- 20153466
TI  - [Severe pneumonia due to influenza A: any other cause?].

PMID- 20153467
TI  - Cross-border fertility care--International Committee Monitoring Assisted
      Reproductive Technologies global survey: 2006 data and estimates.
AB  - OBJECTIVE: To collect data on the prevalence and reasons for cross-border
      fertility care (CBFC). DESIGN: Retrospective survey conducted by the
      International Committee Monitoring Assisted Reproductive Technologies. SETTING:
      Forty-nine countries who have previously participated with the International
      Committee Monitoring Assisted Reproductive Technologies. PATIENT(S): Number of
      CBFC patients per country. INTERVENTION(S): Questionnaire. MAIN OUTCOME
      MEASURE(S): Number of CBFC patients and reason for travel. RESULT(S): The
      majority of replies were comprised of estimates for incoming and outgoing
      patients having CBFC. The main reasons for leaving a home country for CBFC
      included treatment anonymity and legality issues, whereas incoming patients most
      often traveled due to efficacy and access. CONCLUSION(S): Few countries are able
      to quantify numbers of patients having CBFC, although our data suggest that
      incoming treatment seekers are more easily numerated due to clinic registration
      procedures. Standardization of data collection and creation of national databases
      are needed to collect quantitative information that will help reproductive
      caregivers to provide support for patients having CBFC.

PMID- 20153468
TI  - Evaluation of erythrocyte band 3 phosphotyrosine level, glutathione content, CA
      125, and human epididymal secretory protein E4 as combined parameters in
      endometriosis.
AB  - OBJECTIVE: To investigate the biochemical parameters of the erythrocyte response
      to diamide-induced oxidative stress, alone or as adjuncts to serum values of CA
      125 and human epididymal secretory protein E4 (HE4), in the diagnosis and study
      of endometriosis. SETTING: University of Padova. DESIGN: Prospective study.
      PATIENT(S): Forty-five patients of reproductive age undergoing laparoscopy.
      INTERVENTION(S): All women were studied for endometriotic foci during
      laparoscopic surgery. Forty-one had laparoscopically and histologically confirmed
      endometriosis, and four did not. Twenty women with confirmed endometriosis were
      reassessed 1-4 months later. MAIN OUTCOME MEASURE(S): CA-125 and HE4 and two new
      parameters evaluated in erythrocytes after diamide-induced stress, that is, band
      3 tyrosine phosphorylation (Tyr-P) level and decrease in total glutathione
      content (DeltaGSH), were assessed in all patients. RESULT(S): In association with
      serum CA-125 levels but not with HE4, diamide-related erythrocyte band 3 Tyr-P
      and DeltaGSH were significantly higher in patients with endometriosis and were
      able to discriminate with high sensitivity and specificity between patients
      before and after surgery. CONCLUSION(S): Endometriosis is associated with an
      increase in systemic oxidative stress, affecting the antioxidative defenses of
      circulating erythrocytes. All related implications, including evaluation of other
      oxidative stress-related changes, warrant further study.

PMID- 20153469
TI  - Nerve fibers in ovarian endometriomas.
AB  - Ovarian endometriomas (n = 29) were innervated by mainly sympathetic and sensory
      fibers. These fibers may be involved in the generation of pain symptoms.

PMID- 20153470
TI  - Surrogate end points in women's health research: science, protoscience, and
      pseudoscience.
AB  - A surrogate end point (e.g., a laboratory test or image) serves as a proxy for a
      clinical end point of importance (e.g., fracture, thrombosis, or death). Adoption
      and use of surrogate end points lacking validation, especially in cardiovascular
      medicine, have caused thousands of patients' deaths, a serious violation of the
      ethical principle of beneficence.

PMID- 20153471
TI  - Persistent cognitive depressive symptoms are associated with coronary artery
      calcification.
AB  - OBJECTIVES: The association between depression and sub-clinical atherosclerosis
      remains unclear. By assessing depressive symptoms only at one point in time, most
      previous studies have failed to ascertain long-term exposure. We examined the
      association of long-term depressive symptoms assessed at three time points (over
      10 yrs) with a marker of sub-clinical atherosclerosis. METHODS: Participants
      included 454 healthy, non-medicated men and women from the Whitehall II
      epidemiological cohort without known cardiovascular disease (CVD). Depressive
      symptoms were assessed at three time points (over 10 yrs) and coronary
      atherosclerosis was assessed at follow-up in terms of coronary artery
      calcification (CAC). RESULTS: 18.9% of the sample reported depressive symptoms at
      least once during follow-up. Participants that were persistently depressed had
      over a two-fold increased risk of detectable CAC (Agatston score>0) (odds ratio
      [OR]=2.56, 95% CI, 1.14-5.78) and high CAC (Agatston score > or = 100) (OR=2.36,
      1.04-5.35) compared with never depressed after adjustment for age, sex, and a
      range of conventional cardiac risk factors. These associations were more robust
      in men. Participants who were depressed on only one occasion were not at elevated
      risk of CAC. CONCLUSIONS: Persistent cognitive symptoms of depression assessed
      over several time points, but not on a single occasion, are related to sub
      clinical coronary atherosclerosis in men free of known CVD and diabetes.

PMID- 20153472
TI  - ESR1 genetic variants, haplotypes and the risk of coronary heart disease and
      ischemic stroke in the Finnish population: a prospective follow-up study.
AB  - Association of estrogen receptor 1 (ESR1) gene variants and risk of coronary
      heart disease (CHD) and ischemic stroke was evaluated in the FINRISK-study. From
      14,140 individuals, 2225 were selected for genotyping using a case-cohort design.
      Time-to-event analysis showed that the CC genotype of -397T/C ERS1 gene
      contributed to higher risk of CHD only in men (HR, 1.68, CI 1.03-2.74). The 
      351A/G polymorphism was not independently associated with CHD. Haplotype analysis
      of these two variants indicated that in men, haplotype TA conferred lower risk of
      CHD (HR=0.72, CI 0.55-0.95), whereas men with haplotype CA had 1.8 higher risk of
      CHD events (CI 1.21-2.77), compared to other haplotypes. No association was found
      with ischemic stroke. Our study suggests that the minor allele -397C of the ESR1
      gene confers risk of CHD among Finnish men, both in homozygous state and as part
      of a haplotype with the -351A allele.

PMID- 20153473
TI  - Association of plaque in the carotid and coronary arteries, using MDCT
      angiography.
AB  - OBJECTIVE: Associations between various plaque types in coronary and carotid
      arteries using multidetector row computed tomography (MDCT) have not yet been
      reported. We evaluated MDCT correlation of total plaque and various plaque
      subtypes in carotid and coronary arteries. METHODS: We studied 62 patients who
      had both carotid and cardiac computed tomography angiography (CTA). The plaque in
      each vascular segment was classified as non-calcified, calcified or mixed.
      RESULTS: The average age of this population was 68+/-22 years, 63% males. Total
      plaque in the carotid artery correlated with total, calcified and mixed plaque in
      the coronary artery (all P<0.001). Calcified plaque in the carotid artery was
      associated with total and calcified plaque in the coronary bed (P<0.001). Non
      calcified coronary plaque was not associated with carotid plaque. CONCLUSION:
      Total plaque in coronary and carotid arteries are highly correlated.

PMID- 20153474
TI  - A high performance liquid chromatography-electrochemical array method for the
      measurement of oxidative/nitrative changes in human urine.
AB  - Oxidative stress has been implicated in various pathologies as well as in
      environmental pollutant-induced negative health outcomes. In this work we have
      developed an analytical method to measure oxidative stress markers namely m-, o
      tyrosine, 3-chlorotyrosine, 3-nitrotyrosine, and the DNA damage marker 8-hydroxy
      deoxyguanosine in human urine. The method involves the base hydrolysis of the
      urine sample followed by solid phase extraction of target analytes using a
      reverse phase polymeric sorbent column prior to the HPLC-EC analysis. The
      recovery studies indicated that the overall method recovery for all analytes were
      >60%. The limit of quantification of all target analytes was <10nM with a linear
      range from 2 nM to 150 microM. The applicability of this method is demonstrated
      by analyzing the above markers in healthy human urine (n=10) samples.

PMID- 20153475
TI  - Retention indices and quantum-chemical descriptors of aromatic compounds on
      stationary phases with chemically bonded copper complexes.
AB  - In this paper, Kovats retention indices determined on stationary phases with
      chemically bonded copper complexes were correlated with molecular structural
      parameters for aromatic compounds. Principal component regression (PCR) was
      applied to extract principal components from the set of 13 descriptors compiled
      in 5 theoretical models. Extracted components were used to model theoretical
      retention indices. Significant correlations were found among the retention
      indices of these compounds and, among others: molecular surface and molecule
      area, boiling point, HOMO and LUMO energies, dipole moment, dielectric energy,
      and double bond count. These correlations provide insights into the mechanism of
      chromatographic retention at the molecular level for the packings and the
      compounds under study.

PMID- 20153476
TI  - A high throughput dried DMSO LogD lipophilicity measurement based on 96-well
      shake-flask and atmospheric pressure photoionization mass spectrometry detection.
AB  - A rapid throughput octanol-water lipophilicity measurement based on 96-well shake
      flask and LC/UV/APPI/MS is described. The method utilizes central liquid storage
      where compounds are stored as 10 mM solutions in dimethyl sulfoxide (DMSO). The
      DMSO is subsequently removed to generate solid like material used for LogD
      measurement. The removal of DMSO minimizes the concern for potential DMSO
      cosolvent effect on the measured value. Sample preparation is automated using a
      liquid handling workstation with 96-well pipetter. Both octanol and buffer phases
      are quantified using state of the art ultra-high pressure HPLC coupled with a
      superficially diffused core reversed-phase column and an atmospheric pressure
      photo ionization mass spectrometer. The throughput of the method is two days for
      a batch of 96 compounds. The method has been validated using 72 literature
      compounds with diverse ionization and LogD values ranging from -2 to +6. The
      observed coefficient of determination r(2) is 0.9973.

PMID- 20153477
TI  - Impact of the antimicrobial peptide Novicidin on membrane structure and
      integrity.
AB  - We have studied the impact of an 18-residue cationic antimicrobial peptide
      Novicidin (Nc) on the structure and integrity of partially anionic lipid
      membranes using oriented circular dichroism (OCD), quartz crystal microbalance
      with dissipation (QCM-D), dual polarization interferometry (DPI), calcein dye
      leakage and fluorescence spectroscopy. OCD consistently showed that Nc is bound
      in an alpha-helical, surface bound state over a range of peptide to lipid (P/L)
      ratios up to ~1:15. Realignment of Nc at higher P/L ratios correlates to loss of
      membrane integrity as shown by Laurdan fluorescence spectroscopy and by loss of
      lipid alignment in DPI analysis. Laurdan generalized polarity shows a decrease in
      water accessibility or mobility in the hydrophobic/hydrophilic interface of the
      lipid membrane, consistent with rearrangement of lipid packing. QCM-D studies on
      the interaction of Nc with lipid membranes emphasize the importance of including
      the dissipation factor in data analysis, revealing formation of a highly hydrated
      film after exposure to >=3 MUM Nc. Our findings suggest a carpet mechanism of
      membrane disruption in which peptide binding first induces leakage at a critical
      surface concentration, probably through formation of transient pores or transient
      disruption of the membrane integrity, followed by more extensive membrane
      disintegration at higher P/L ratios.

PMID- 20153478
TI  - The effect of calcium ions and sodium silicate on the adsorption of a model
      anionic flotation collector on magnetite studied by ATR-FTIR spectroscopy.
AB  - Previous studies have shown that agglomeration of the magnetite concentrate after
      reverse flotation of apatite is negatively affected by the collector species
      adsorbed on the surface of magnetite. In this work, the effect of ionic strength,
      calcium ions and sodium silicate on the unwanted adsorption of a model anionic
      flotation collector on synthetic magnetite was studied in situ using attenuated
      total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The amount
      of collector adsorbed was found to increase with increasing ionic strength at pH
      8.5 providing evidence to the contribution of electrostatic forces to the
      adsorption of the collector. Adding sodium silicate to the system resulted in a
      threefold decrease in the amount of collector adsorbed compared to when no sodium
      silicate was added, confirming the depressing activity of sodium silicate on
      magnetite. Calcium ions were shown to increase the adsorption of both the
      collector and sodium silicate on magnetite. The depressing effect of sodium
      silicate on collector adsorption was completely suppressed in the presence of
      calcium ions under the conditions studied. Furthermore, the amount of collector
      adsorbed on magnetite from the silicate-collector solution increased 14 times
      upon addition of calcium ions suggesting that calcium ions in the process water
      may increase undesired adsorption of the collector on the iron oxide.

PMID- 20153479
TI  - Synthesis and cytotoxicity assessment of superparamagnetic iron-gold core-shell
      nanoparticles coated with polyglycerol.
AB  - Core-shell iron-gold (Fe@Au) nanoparticles were synthesized by a facile reverse
      micelle procedure and the effect of water to surfactant molar ratio (w) on the
      size, size distribution and magnetic properties of the nanoparticles was studied.
      MTT assay was utilized to evaluate the cell toxicity of the nanoparticles. To
      functionalize the particles for MRI imaging and targeted drug delivery, the
      particles were coated by polyglycerol through capping with thiol followed by
      polymerization of glycidol. The characteristics of the particles were examined by
      X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample
      magnetometer (VSM), UV-visible spectroscopy, and Fourier transform infrared
      spectroscopy (FT-IR). It was found that the size and size distribution of the
      nanoparticles increase by increasing the water to surfactant molar ratio (w). The
      particles were spherical in shape with a thin layer of gold. Complementary growth
      of the gold shell on the iron core was noticed. Meanwhile, two types of
      agglomeration including magnetic beads and magnetic colloidal nanocrystals
      clusters were observed dependent on the w-value. The magnetic measurement studies
      revealed the superparamagnetic behavior of the nanoparticles. MTT assay result
      indicated the synthesized nanoparticles are nontoxic that will be useful for
      biomedical applications.

PMID- 20153480
TI  - Characterization of strains of ovine transmissible spongiform encephalopathy with
      a short PrPd profiling method.
AB  - Scrapie is the transmissible spongiform encephalopathy (TSE) that naturally
      affects sheep and goats; these species are also susceptible to experimental
      infection with the bovine spongiform encephalopathy (BSE) agent. Discrimination
      between different strains of sheep scrapie and ovine BSE has been achieved by
      descriptive and quantitative profiling of deposits of the disease-associated
      prion protein (PrPd) in different areas of the brain, but this process is time
      consuming and difficult to standardize between laboratories. The present paper
      describes an alternative PrPd profiling method that is less demanding and
      addresses these difficulties. It is based on the scoring of similar 14 PrPd types
      in 11 precisely defined areas of the telencephalon. When applied to 48 archived
      cases of experimental sheep BSE, SSBP/1, CH1641 and natural scrapie, it gave
      comparable results to the original profiling method, previously conducted on the
      same brains, and allowed differentiation between the different infectious
      sources. This new 'short PrPd profiling' method has the advantages of being less
      time-consuming and easier to standardize, so that it can be readily adopted by
      different laboratories to provide comparable results.

PMID- 20153481
TI  - The development of analogy making in children: cognitive load and executive
      functions.
AB  - The aim of the current study was to investigate the performance of 6-, 8-, and 14
      year-olds on an analogy-making task involving analogies in which there are
      competing perceptual and relational matches. We hypothesized that the selection
      of the common relational structure requires the inhibition of other salient
      features, in particular, perceptual matches. Using an A:B::C:D paradigm, we
      showed that children's performance in analogy-making tasks depends crucially on
      the nature of the distractors. Children chose more perceptual distractors having
      a common feature with C compared with A or B (Experiment 1). In addition, they
      were also influenced by unstructured random textures. When measuring reaction
      times instead of accurate responses, only the 8-year-olds' reaction times were
      significantly influenced by perceptual distractors. The 6-year-olds seemed to
      select the first match they noticed, and the 14-year-olds were not influenced (or
      much less influenced) by featural distractors. These results are compatible with
      an analogy-making account based on varying limitations in executive functioning
      at different ages.

PMID- 20153482
TI  - Low-frequency repetitive transcranial magnetic stimulation and off-phase motor
      symptoms in Parkinson's disease.
AB  - Repetitive transcranial magnetic stimulation (rTMS) can modulate cortical
      excitability and activation and consequently may affect clinical symptoms in
      neurological conditions characterized by altered motor cortex functions. There
      are conflicting reports whether low-frequency rTMS has any clinical effects in
      Parkinson's disease (PD). Ten patients with PD had rTMS (1800 stimuli at just
      below active motor threshold intensity) at 1Hz rate delivered over the motor
      cortex for four consecutive days on two separate occasions. On one of these real
      rTMS was used and on the other sham rTMS (placebo) was used. Evaluations with
      UPDRS Part 3 (Motor Scale) were done in practically defined off-phase at the
      baseline and one day after the end of each of the treatment series. Neither total
      Motor Scale scores nor subscores for axial symptoms, rigidity, bradykinesia, and
      tremor showed any significant difference. The results do not confirm presence of
      residual beneficial clinical after-effects of consecutive daily applications of
      low-frequency rTMS on motor symptoms in PD, at least when 1800 stimuli at
      subthreshold intensity are applied for four days.

PMID- 20153483
TI  - Distribution, transport and exchanges of fine sediment, with tidal power
      implications: Severn Estuary, UK.
AB  - The Severn, a hypertidal, high turbidity estuary, has a bed largely stripped of
      unconsolidated sediment. Its inter-tidal zone is mainly mudflats, the universal
      erosional trend of which is now proven. These are a source for sub-tidal mud
      accumulations in Newport Deep, much of Bridgwater Bay, less so in Bristol Deep
      and Cardiff Roads. The main estuary turbidity maximum is dominated by its
      exceptional turbidity and the cycling of this on two tidal timescales. It is the
      means to exchange fines between sources and sinks. It shows discontinuities in
      three planes - lutoclines, suspended sediment fronts and slug flow. Much of the
      estuary is verging on or actually barren. It has been designated under EU
      legislation for its fine sediment-induced naturally-depauperate nature. This is
      invalid as it is complicated by large scale ecosystem collapse due to climate
      change. Building a Cardiff-Weston barrage would induce a large rise in faunal
      abundance and biodiversity.

PMID- 20153484
TI  - Birds of the Severn Estuary and Bristol Channel: their current status and key
      environmental issues.
AB  - The Severn Estuary and Bristol Channel encompass a number of designated sites
      supporting populations of waterbirds and seabirds that are of national or
      international importance, including the Severn Estuary and Burry Inlet Special
      Protection Areas (SPAs)/Ramsar Sites and Carmarthen Bay, the UK's first marine
      SPA. Here, we provide an overview of the present numbers and trends of the
      waterbirds and seabirds using these sites, updating previous reviews undertaken
      prior to these designations. We further provide a summary of the main issues that
      have affected the status of the area's bird populations. Declines in the numbers
      of waders on the Severn Estuary and the southwest over the last two decades have
      been linked to climate change. The Sea Empress oil-spill impacted both breeding
      seabirds and the wintering Common Scoters in Carmarthen Bay, though numbers of
      the latter recovered 3years after the spill. At the Burry Inlet, Oystercatcher
      numbers have fallen over the last 25years and considerable research has been
      undertaken into the conflict with cockle and mussel fisheries. A long-term study
      at Cardiff Bay, at the mouth of the Severn, revealed a significant impact on the
      survival of Redshanks following its impoundment and has helped to further
      understanding of responses of waterbirds to estuarine habitat loss. The potential
      impacts of the construction of a tidal power scheme on the Severn Estuary are
      also discussed.

PMID- 20153485
TI  - A review of sediment dynamics in the Severn Estuary: influence of flocculation.
AB  - This paper provides a review and critique of the distributions and
      characteristics of non-cohesive and cohesive sediments within the Severn Estuary,
      with particular reference to floc properties. The estuary is hyper-tidal and,
      consequently, highly turbid along most of its length and it generally has two
      turbidity maxima. In the upper reaches of the estuary, suspended particulate
      matter (SPM) concentrations can be in excess of 10 g l(-1) for river flows up to
      50 m(3)s(-1), rising to over 50 g l(-1) during periods of lower river flow. The
      lower estuary turbidity maximum originates in the vicinity of Bridgwater Bay
      where SPM concentrations may vary between 0.1-200 g l(-1). The formation of fluid
      mud is coupled to the spring-neap cycle and strong vertical gradients in SPM
      concentrations produce turbulence damping and drag reduction effects, and hence
      impair the ability of the flow to transport sediments. Flocculation is an
      important mechanism for controlling the behaviour of fine sediments and mean
      settling velocities of flocs vary between 0.8-6 mm s(-1). A secondary consequence
      of flocculation is the formation of mud:sand mixtures in turbid suspensions.
      Improved understanding of the significance of flocculation processes is crucial
      as they may exert an influence on the mechanism by which adsorbed contaminants
      are transported in the system.

PMID- 20153486
TI  - Undermining the integrated maritime policy.
AB  - The European Union's Integrated Maritime Policy is intended in part to co
      ordinate sectoral policies, to achieve joined-up thinking and action and overcome
      the inconsistency between policy approaches that has led to the degradation of
      European seas. An integrated governance would be relatively straight-forward if
      the different interests and actors were operating on the basis of shared values,
      but they are not. While the fisheries sector, whether large or small-scale, is
      driven by a commercial imperative which tends towards the greatest extraction of
      the resource possible, environmentalists would champion the removal of all human
      impacts, other than redress activity, as the optimum state for the ecosystem.
      However, the greatest impediment to an integrated approach is the failure to
      subject the EU's Common Fisheries Policy to the objectives of the Integrated
      Maritime Policy. Instead, all decisions concerning fisheries will continue to be
      made in accordance with the Fisheries Regulation which demands exploitation of
      the fragile resource. Attention needs to be given to how EU fisheries policy is
      to acquire values beyond that of commercial extraction for immediate economic
      benefit so that it may cohere with objectives of the Integrated Maritime Policy
      and aid the regeneration of the seas.

PMID- 20153487
TI  - Effect of 2 weeks of sprint interval training on health-related outcomes in
      sedentary overweight/obese men.
AB  - The aim of this study was to investigate the effects of very high intensity
      sprint interval training (SIT) on metabolic and vascular risk factors in
      overweight/obese sedentary men. Ten men (age, 32.1 +/- 8.7 years; body mass
      index, 31.0 +/- 3.7 kg m(-2)) participated. After baseline metabolic,
      anthropometric, and fitness measurements, participants completed a 2-week SIT
      intervention, comprising 6 sessions of 4 to 6 repeats of 30-second Wingate
      anaerobic sprints on an electromagnetically braked cycle ergometer, with 4.5
      minute recovery between each repetition. Metabolic, anthropometric, and fitness
      assessments were repeated post-intervention. Both maximal oxygen uptake (2.98 +/-
      0.15 vs 3.23 +/- 0.14 L min(-1), P = .013) and mean Wingate power (579 +/- 24 vs
      600 +/- 19 W, P = .040) significantly increased after 2 weeks of SIT. Insulin
      sensitivity index (5.35 +/- 0.72 vs 4.34 +/- 0.72, P = .027) and resting fat
      oxidation rate in the fasted state (0.13 +/- 0.01 vs 0.11 +/- 0.01 g min(-1), P =
      .019) were significantly higher and systolic blood pressure (121 +/- 3 vs 127 +/-
      3 mm Hg, P = .020) and resting carbohydrate oxidation in the fasted state (0.03
      +/- 0.01 vs 0.08 +/- 0.02 g min(-1), P = .037) were significantly lower 24 hours
      post-intervention compared with baseline, but these changes were no longer
      significant 72 hours post-intervention. Significant decreases in waist (98.9 +/-
      3.1 vs 101.3 +/- 2.7 cm, P = .004) and hip (109.8 +/- 2.2 vs 110.9 +/- 2.2 cm, P
      = .017) circumferences compared with baseline were also observed after the
      intervention. Thus, 2 weeks of SIT substantially improved a number of metabolic
      and vascular risk factors in overweight/obese sedentary men, highlighting the
      potential for this to provide an alternative exercise model for the improvement
      of vascular and metabolic health in this population.

PMID- 20153488
TI  - Does long-term metformin treatment increase cardiac lipoprotein lipase?
AB  - Acute activation of adenosine monophosphate-activated protein kinase (AMPK) or
      jumps in cardiac work increased cardiac endothelial lipoprotein lipase (LPL), yet
      it is unclear whether chronic AMPK activation maintains this elevated LPL. To
      activate AMPK chronically, metformin at low (300 mg/kg/d) and high dose (600
      mg/kg/d) was administered in drinking water for 14 days. Control, metformin
      treated, and 5-amino-imidazole-4-carboxamide riboside (AICAR)-treated (0.5
      mmol/L) ex vivo hearts were perfused to investigate uptake of triacylglycerol and
      cardiac LPL activity. For perfused rat hearts, increased uptake of labeled
      Intralipid and beta-oxidation of Intralipid-fatty acid were noted for both AICAR
      (P < .05) and high-dose metformin (P < .01). Intralipid incorporation into tissue
      lipids was decreased by AICAR (P < .05) and increased after high-dose metformin
      (P < .05), the increase manifest as enhanced triacylglycerol deposition (P <
      .05). Low-dose metformin did not alter lipid uptake or tissue deposition. Both
      high-dose metformin and AICAR decreased cardiac acetyl-coenzyme A carboxylase
      activity (P < .01). Heparin-releasable LPL was increased after treatment with
      AICAR (P < .05) and high-dose metformin (P < .01). Low-dose metformin did not
      alter cardiac LPL. High-dose metformin doubled immunoreactive AMPK and phospho
      AMPK protein (P < .001) and increased phosphorylation of p38-mitogen-activated
      protein kinase (P < .05). After heparin pretreatment, the rate of recruitment of
      LPL to the cardiac endothelium was increased by AICAR (P < .05) but not by high
      dose metformin. These data suggest that AMPK activation increased cardiac
      endothelial LPL, yet acute and chronic activation of AMPK may yield increased LPL
      through differing mechanisms.

PMID- 20153489
TI  - Effects of diabetes family history and exercise training on the expression of
      adiponectin and leptin and their receptors.
AB  - Daughters of diabetes patients have lower insulin sensitivity than women with no
      diabetes family history, but increase insulin sensitivity to a greater extent
      with exercise training. This study aimed to determine whether differences in
      circulating concentrations of adiponectin and leptin, and adipose tissue
      expression of their genes and receptors played a role. Women offspring of
      patients with type 2 diabetes mellitus (n = 34; age, 35.6 +/- 7.0 years; body
      mass index, 28.1 +/- 5.1 kg/m2) and matched controls with no diabetes family
      history (n = 36; age, 33.6 +/- 6.1 years; body mass index, 27.3 +/- 4.7 kg/m2)
      participated. Blood and abdominal subcutaneous adipose tissue samples were
      obtained at baseline and after a controlled 7-week endurance-type exercise
      intervention (sessions were performed at 65%-80% of maximum heart rate). At
      baseline, no significant differences were observed between groups in circulating
      leptin or adiponectin concentrations, or expression of their genes or receptors.
      In response to exercise, plasma leptin decreased more in offspring than controls
      (-32.2% vs -7.3%, P = .005 for interaction); and the long isoform of the leptin
      receptor messenger RNA (mRNA) increased significantly only in the offspring
      (+39.4%, P = .026 vs +7.7%, P = .892). Leptin mRNA decreased similarly in both
      groups (-24.7% vs -25.0%, P < .05 for both). Furthermore, changes in plasma
      leptin (r = -0.432, P < .001) and leptin mRNA (r = -0.298, P = .019) correlated
      significantly with changes in insulin sensitivity. Plasma adiponectin decreased
      similarly in both groups (-12.1% vs -15.2%, P < .01 for both), but no significant
      changes were observed in adiponectin-related gene expression. This work shows
      that exercise training has differing effects on leptin-related variables between
      women with and without a diabetes family history and suggests that these
      molecular differences may contribute to the differential effects of exercise
      training on insulin sensitivity between these 2 groups.

PMID- 20153490
TI  - Assessment of non-insulin-mediated glucose uptake: association with body fat and
      glycemic status.
AB  - In the fasting state, approximately 83% of glucose uptake occurs via non-insulin
      mediated mechanisms. A widely accepted static rate for NIMGU is 1.62 mg kg(
      1).min(-1). To investigate the variability of NIMGU, we examined differences by
      glucose tolerance, sex, age, race (American Indian/African American/Caucasian),
      and adiposity in 616 volunteers (including individuals with normal glucose
      regulation [NGR] and impaired glucose regulation [IGR] and diabetes mellitus
      [DM]) using data from euglycemic-hyperinsulinemic clamp experiments. NIMGU was
      determined by plotting basal glucose output and insulin action against fasting
      and steady-state clamp insulin. The intercept with the y-axis after extrapolation
      was interpreted as NIMGU at zero insulin. Body composition was determined by dual
      energy x-ray absorptiometry; and glucose regulation, by a 75-g oral glucose
      tolerance test. Energy expenditure was measured by indirect calorimetry in a
      metabolic chamber. In individuals with NGR (n = 385), NIMGU was 1.63 mg
      kg(estimated metabolic body size (fat free mass + 17.7 kg))(-1) min(-1) (95%
      confidence interval, 1.59-1.66). NIMGU increased with IGR and DM (IGR: n = 189,
      1.67 [1.62-1.72]; DM: n = 42, 2.39 [2.29-2.49]; P < .0001 across groups). NIMGU
      did not differ by sex (P = .13), age (P = .22), or race (P = .06); however, NIMGU
      was associated with percentage body fat (r(2) = 0.04, P < .0001). Furthermore,
      NIMGU was positively associated with 24-hour and sleep energy expenditure (r(2) =
      0.002, P = .03; r(2) = 0.01, P < .01). Extrapolated NIMGU in individuals with NGR
      is remarkably consistent with previously published data. Our results indicate
      that NIMGU is associated with adiposity. NIMGU increases with declining glucose
      tolerance perhaps to preserve glucose uptake during increased insulin resistance.

PMID- 20153491
TI  - Demonstration of increased toll-like receptor 2 and toll-like receptor 4
      expression in monocytes of type 1 diabetes mellitus patients with microvascular
      complications.
AB  - Type 1 diabetes mellitus (T1DM) is associated with increased microvascular
      complications and is a proinflammatory state. The toll-like receptors (TLRs) are
      pattern recognition receptors on monocytes and important in atherosclerosis. We
      have shown increased TLR2 and TLR4 expression on monocytes of T1DM compared with
      controls. In this report, we tested the surface expression of TLR2 and TLR4 on
      monocytes of T1DM patients with microvascular complications (T1DM-MV) compared
      with those without (T1DM) and healthy controls. The study was performed at the
      University of California Davis. Healthy controls (n = 31), T1DM patients (n =
      31), and T1DM-MV patients (n = 34) were included. The TLR2 and TLR4 surface
      expression was significantly increased in T1DM-MV monocytes compared with T1DM
      and controls (P < .01). In addition, nuclear factor kappaB activity and
      interleukin-1beta release were significantly increased in monocytes from T1DM-MV
      compared with T1DM (P < .005). Thus, we make the novel observation that TLR2 and
      TLR4 expression and signaling are increased in T1DM-MV compared with T1DM and may
      contribute to the accentuated proinflammatory state and complications of T1DM.

PMID- 20153492
TI  - Effects of adrenaline on whole-body glucose metabolism and insulin-mediated
      regulation of glycogen synthase and PKB phosphorylation in human skeletal muscle.
AB  - In the present study, we investigated the effect of adrenaline on insulin
      mediated regulation of glucose and fat metabolism with focus on regulation of
      skeletal muscle PKB, GSK-3, and glycogen synthase (GS) phosphorylation. Ten
      healthy subjects (5 men and 5 women) received a 240-minute intravenous infusion
      of adrenaline (0.05 MUg/[kg min]) or saline; after 120 minutes, a
      hyperinsulinemic-euglycemic clamp was added. Adrenaline infusion increased blood
      glucose concentration by approximately 50%, but the hyperinsulinemic clamp
      normalized blood glucose within 30 minutes. Glucose infusion rate during the last
      hour was approximately 60% lower during adrenaline infusion compared with saline
      (4.3 +/- 0.5 vs 11.2 +/- 0.6 mg/kg lean body mass per minute). Insulin increased
      PKB Ser473, PKB Thr308, and GSK-3beta Ser9 phosphorylation in skeletal muscles;
      coinfusion of adrenaline did not influence insulin-stimulated PKB and GSK-3
      phosphorylation. Adrenaline alone did not influence phosphorylation of PKB and
      GSK-3beta. Insulin increased GS fractional activity and decreased GS Ser641 and
      Ser645,649,653,657 phosphorylation. In the presence of adrenaline, insulin did
      neither activate GS nor dephosphorylate GS Ser641. Surprisingly, GS Ser7
      phosphorylation was not influenced by adrenaline. Adrenaline increased plasma
      lactate concentration; and muscle glycogen content was reduced in skeletal muscle
      the day after adrenaline infusion, supporting that insulin does not stimulate
      glycogen synthesis in skeletal muscles when adrenaline is present. In conclusion,
      adrenaline did not influence basal or insulin-stimulated PKB and GSK-3beta
      phosphorylation in muscles, but completely blocked insulin-mediated GS activation
      and Ser641 dephosphorylation. Still, insulin normalized adrenaline-mediated
      hyperglycemia.

PMID- 20153493
TI  - Canine ABCB4: Tissue expression and cDNA structure.
AB  - The ABCB gene subfamily of ABC (ATP-binding cassette) transporters is responsible
      for transporting a wide spectrum of molecules including peptides, iron, bile
      salts, drugs, and phospholipids. In humans, ABCB4 appears to be exclusively
      expressed on the apical membrane of hepatocytes where it translocates
      phosphatidylcholine from the inner to the outer leaflet of the canalicular
      membrane. Functional alterations in the ABCB4 transporter are associated with a
      number of cholestatic syndromes in humans. Because of its role in biliary lipid
      homeostasis in humans, investigation of the ABCB4 gene in dogs is warranted.
      Thus, the full cDNA sequence of canine ABCB4 was elucidated and its mRNA and
      protein expression levels in tissues were determined. Canine ABCB4 consists of
      3804 nucleotides spanning 26 exons and is 89% identical to human ABCB4.
      Expression of ABCB4 in canine liver supports a potential role for the protein in
      normal biliary function similar to that in humans. The function of ABCB4
      expressed in brain tissue has yet to be determined.

PMID- 20153494
TI  - Effects of anionic salts supplementation on blood pH and mineral status, energy
      metabolism, reproduction and production in transition dairy cows.
AB  - The objectives of this study were to determine the effects of a pre-partum diet
      with lower than recommended (DCAD=-82 mEq/kg of dietary DM) amounts of anionic
      salts on metabolism, health, reproductive performance and milk production in
      dairy cows. Sixty Holstein multiparous cows were enrolled 21 days prior to
      expected calving date. The animals were randomly assigned to receive one of two
      rations: 30 cows received anionic ration [-82 mEq (NA+K-Cl-S)/kg of DM] for 21 d
      to parturition and the other group (n=30) were fed a usual dry period ration
      (+192 mEq/kg of DM). Serum samples obtained at days -21, +3 and +21 relative to
      calving were analyzed for beta-hydroxybutyrate (BHBA), non-esterified fatty acids
      (NEFA), glucose, calcium (Ca), inorganic phosphorus, magnesium, chloride, sodium,
      potassium, cholesterol, urea, creatinine, total protein, albumin, and aspartate
      aminotransferase (AST). Urine pH declined from 8.4 at 21 d before calving (pre
      treatment) to 6.2 at day 7 pre-partum in the treatment group. Repeated-measure
      mixed model analysis indicated that the concentrations of Ca were significantly
      increased and creatinine, and AST were significantly decreased by lowering DCAD.
      The concentrations of BHBA, NEFA and glucose were not affected by treatment. The
      incidence of milk fever and culling were 5 and 11 times higher in the control
      group in comparison with the treatment group, respectively. The intervals from
      calving to first breeding and to pregnancy were not influenced by treatment.
      There was no group effect on average daily milk yield or fat percentage.

PMID- 20153496
TI  - Transient perioperative pharmacologic inhibition of muscularis macrophages as a
      target for prophylaxis of postoperative ileus does not affect anastomotic healing
      in mice.
AB  - BACKGROUND: Postoperative ileus is mediated through a severe inflammation of the
      tunica muscularis. Inhibition of initially involved muscularis macrophages could
      be a promising clinical approach to prevent postoperative ileus. The aim of this
      study was to investigate whether pharmacologic or genetic depletion of these
      inflammatory cells influences anastomotic healing. METHODS: Standardized ileal
      anastomoses were performed and the mice were randomized into 4 groups: (1) wild
      type; (2) pharmacologically depleted and inactivated, by means of chlodronate
      liposomes and gadolinium chloride; (3) heterozygous osteopetrosis littermates;
      (4) genetically depleted osteopetrosis mutant mice. Tissues from the anastomoses
      were removed 2, 5, and 14 days after surgery and used for molecular (collagen 1
      and 3, matrix metalloproteinases 2, 9, and 13 expressions), histochemical
      (anastomotic healing score, cross polarization microscopy) and functional
      (anastomotic bursting pressure) investigations. RESULTS: RT-PCR measurements
      demonstrated that the investigated genetic events were similar between controls
      and macrophage-depleted groups. Comparison of histologic healing scores and
      bursting pressure values showed no significant differences between the groups.
      Finally, cross polarization microscopy on picrosirius-red stained sections
      revealed no obvious disturbance in production and deposition of collagen.
      CONCLUSION: In our current model we demonstrate that transient perioperative
      pharmacologic and genetic muscularis macrophage inhibition does not affect
      intestinal anastomotic healing. These results call for further investigations to
      establish a pharmacologic prophylaxis for the prevention of postoperative ileus.

PMID- 20153495
TI  - Incidence and risk factors for community-acquired hepatitis C infection from
      birth to 5 years of age in rural Egyptian children.
AB  - A prospective study in three Egyptian villages (A, B and C) having a high
      prevalence of hepatitis C virus (HCV) infection examined incidence of community
      acquired HCV infection in children; 2852 uninfected infants were prospectively
      followed from birth for up to 5.5 years. Fifteen seroconverted for either HCV
      antibodies and/or HCV-RNA (incidence of 0.53%). Ten had both anti-HCV and HCV
      RNA; four had only anti-HCV; and one had HCV-RNA in the absence of antibody. The
      incidence rate at all ages was 2.7/1000 person-years (PY). It was 3.8/1000 PY
      during infancy and 2.0/1000 PY for the 1-5-years age group. Hospitalization and
      low birth weight increased the risk of infection; while living in village B, the
      family having a higher socioeconomic status, and advanced maternal education were
      protective. Six of eight HCV-infected infants reported iatrogenic exposures (e.g.
      hospitalization, therapeutic injections, ear piercing) prior to infection whereas
      only 2/7 children older than 1 year reported these exposures. Having an HCV
      positive mother was the only other reported risk in two of these older children.
      The virus cleared in six (40%) children by the end of follow-up. Health education
      targeting iatrogenic exposures and focusing on risk factors could reduce HCV
      infection in children in high-risk populations.

PMID- 20153497
TI  - Microbubble mediated sonoporation of cells in suspension: clonogenic viability
      and influence of molecular size on uptake.
AB  - This work investigates whether the application of sonoporation is limited by the
      size of a macromolecule being delivered and by the ability of cells to
      proliferate following uptake. KHT-C cells in suspension were exposed to
      variations in ultrasound pressure (0-570 kPa) and microbubble shell-type (lipid
      and protein) at fixed settings of 500 kHz centre frequency, 32 micros pulse
      duration, 3 kHz pulse repetition frequency and 2 min insonation. Reversible
      permeability (P(R)), defined as the number of cells stained with FITC-dextran and
      unstained with propidium iodide (i.e., PI-viable), was measured with flow
      cytometry for marker molecules ranging from 10 kDa to 2 MDa in size. Viable
      permeability (P(V)) defined as the number of permeabilised cells that maintained
      their ability to proliferate, was measured by clonogenic assay. Comparable
      intracellular delivery of all sizes of molecules was achieved, indicating that
      intracellular delivery of common therapeutic drugs may not be limited by
      molecular size. Maximum P(R)'s of 80% (at 10 kDa) and 55% (at 10 kDa) were
      achieved with lipid coated bubbles at 3.3% v/v and protein coated bubbles at 6.7%
      v/v concentrations. The PI-viability was approximately 80% at 570 kPa in both
      cases. The maximum P(V) achieved with both agents was 22%, while inducing a lower
      overall clonogenic viability with the lipid (39%) compared to the protein (56%)
      shelled bubbles. This study demonstrates that large macromolecules, up to 2 MDa
      in size, can be delivered with high efficiency to cells which undergo reversible
      permeabilisation, maintaining long-term viability in approximately half of the
      cells.

PMID- 20153498
TI  - Estimating the toxicities of organic chemicals in activated sludge process.
AB  - The experimental logEC50 toxicity values of 104 compounds causing bioluminescent
      repression of the bacterium strain Pseudomonas isolated from an industrial
      wastewater were studied. Using the Best Multilinear Regression method implemented
      in CODESSA PRO, models with up to 8 theoretical descriptors were obtained.
      Utilizing a rigorous descriptor selection and validation procedure a reliable
      QSAR model with four parameters was selected as best. The proposed model
      emphasizes the importance of the halogen atoms presented in each compound, the
      possibility of H-bond formation and the flexibility and degree of branching of
      the molecules. As pointed out by many researchers, the contribution of the
      octanol-water partition coefficient to the explanation of the toxicity effect was
      also found to be significant. In addition, the model currently proposed was
      compared to those reported earlier and its advantages were discussed in detail.

PMID- 20153499
TI  - On the role of metabolic activity on the transport und deposition of Pseudomonas
      fluorescens in saturated porous media.
AB  - A study was conducted to understand the role of cell concentration and metabolic
      state in the transport and deposition behaviour of Pseudomonas fluorescens with
      and without substrate addition. Column experiments using the short-pulse
      technique (pulse was equivalent to 0.028 pore volume) were performed in quartz
      sand operating under saturated conditions. For comparison, experiments with
      microspheres and inactive (killed) bacteria were also conducted. The effluent
      concentrations, the retained particle concentrations and the cell shape were
      determined by fluorescent microscopy. For the transport of metabolically-active
      P. fluorescens without substrate addition a bimodal breakthrough curve was
      observed, which could be explained by the different breakthrough behaviour of the
      rod-shaped and coccoidal cells of P. fluorescens. The 70:30 rod/coccoid ratio in
      the influent drastically changed during the transport and it was about 20:80 in
      the effluent and in the quartz sand packing. It was assumed that the active rod
      shaped cells were subjected to shrinkage into coccoidal cells. The change from
      active rod-shaped cells to coccoidal cells could be explained by oxygen
      deficiency which occurs in column experiments under saturated conditions. Also
      the substrate addition led to two consecutive breakthrough peaks and to more
      bacteria being retained in the column. In general, the presence of substrate made
      the assumed stress effects more pronounced. In comparison to microspheres and
      inactive (killed) bacteria, the transport of metabolically-active bacteria with
      and without substrate addition is affected by differences in physiological state
      between rod-shaped and the formed stress-resistant coccoidal cells of P.
      fluorescens.

PMID- 20153500
TI  - An investigation into the N- and C-capping effects of glycine in cavitand-based
      four-helix bundle proteins.
AB  - The capping efficiency of glycine on cavitand-based synthetic four-helix bundles
      was investigated. Glycine, a common C-capping amino acid, has always been
      included as a C-terminal residue in our de novo peptides, although the exact
      contribution of the glyince cap to the overall stability and structure of the
      caviteins had not previously been examined. The uncapped proteins were found to
      be less helical according to their CD spectra. In addition, the H/D exchange
      experiments suggested that the uncapped caviteins were more conformationally
      flexible. Capped and uncapped caviteins exhibited similar deltaG(degrees)(H(2)O)
      values of unfolding. Overall, it can be concluded that glycine caps are useful,
      as they reduce helical unravelling and enhance helicity, and thus, glycine will
      be included as a C-terminal residue in future de novo peptide sequences.

PMID- 20153501
TI  - Halonitromethanes formation in wastewater treatment plant effluents.
AB  - Halonitromethanes (HNMs) constitute one class of emerging disinfection by
      products with high potential health risks. This study investigated the formation
      and occurrence of HNMs under different disinfection scenarios and the presence of
      their precursors in municipal wastewater treatment plant (WWTPs) effluents.
      Formation potential tests performed on WWTP effluents revealed that HNM formation
      occurred in the order of ozonation-chlorination >> ozonation-chloramination >
      chlorination > chloramination. Ozonation alone did not produce any HNM. Municipal
      WWTP effluents contained some reactive HNM precursors, possibly the by-products
      of biological treatment processes and/or some moiety of industry or household
      origin. No effects of nitrate on the formation of HNMs were observed in this
      study, and nitrification in WWTPs appears to remove appreciable portion of HNM
      precursors, especially those reactive to chlorine. UV disinfection using low
      pressure lamps in municipal WWTPs had negligible impact on HNM formation
      potential. HNM concentrations in the effluents of selected WWTPs were either non
      detectable or less than minimum reporting level, except for one WWTP that gave
      trichloronitromethane concentrations in the range of 0.9-1.5 microg L(-1). No
      HNMs were observed in the effluents disinfected with UV radiation. Therefore, it
      appears the typical wastewater disinfection processes involving chlorination or
      UV treatment in WWTPs do not produce significant amounts of HNMs.

PMID- 20153502
TI  - Sensitivity of New Zealand mudsnail Potamopyrgus antipodarum (Gray) to a specific
      aromatase inhibitor.
AB  - The freshwater prosobranch Potamopyrgus antipodarum (Molluska, Hydrobiidea, Smith
      1889) has been proposed as a suitable species to assess the impact of endocrine
      disrupting compounds (EDC) in aquatic ecosystems. Steroid hormone biosynthesis
      pathway is potentially an important target for EDC, and vertebrate-like sex
      steroids seem to play a functional role in the control of mollusk reproduction.
      To assess the response and the sensitivity of P. antipodarum to disrupters of the
      steroid hormone biosynthesis pathway, we have experienced the action of a
      specific vertebrate aromatase inhibitor, fadrozole, acting on 17beta-estradiol
      synthesis in two separate 28 and 42d exposures. Fadrozole had effects consistent
      with the expected mechanism of action. A decrease of the reproduction parameters
      (such as on the number of neonates and number of embryos in the brood pouch) in a
      dose-dependant manner was observed. The steroids levels were also impaired with
      the ratio 17beta-estradiol/testosterone decreased by half in exposed snails. This
      shift of the steroids balance was accompanied by some alteration in the gonads
      histology and immunohistochemistry in fadrozole-exposed snails. This study
      highlights the value role of P. antipodarum as a test species for assessing EDC
      effects in aquatic wildlife.

PMID- 20153503
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptosis of articular chondrocytes
      in culture.
AB  - Positive associations of halogenated aromatic hydrocarbons and arthritis have
      been reported in human populations. Although 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), the most potent congener of its class, is associated with musculoskeletal
      dysfunctions in humans and animals, its role on arthritis remains unknown.
      Apoptosis of chondrocytes has become a focus of interest in the pathogenesis of
      arthritis. We investigated the potential of TCDD as an inducer of chondrocyte
      apoptosis and evaluated its mechanism of action. Rabbit chondrocytes in culture
      were exposed to TCDD. Responses of dioxin-responsive genes and enzyme activity
      were analyzed by RT-PCR and EROD assay, respectively. Generation of reactive
      oxygen species (ROS) and nitric oxide (NO) were also determined. A panel of
      different approaches including caspase-3 assay, ELISA, flow cytometry, and TUNEL
      staining was utilized to detect apoptotic effects. Dioxin induced mRNAs of dioxin
      responsive genes and EROD activity in an AhR-dependent manner. Dose-dependent
      increases in ROS and NO production were observed. All apoptosis detection
      techniques used in this study revealed an increase of apoptotic effects in a dose
      dependent manner. The increase of apoptosis was blocked by inhibitors of ROS or
      NO, suggesting that apoptotic effects may be mediated via ROS- and NO-dependent
      pathways. This is a first report to demonstrate the potential of TCDD to induce
      apoptosis in chondrocytes, which could be an initial process in cartilage
      degradation. This finding may shed a new light in studying the possible role of
      environmental pollutants in the etiology of arthritis.

PMID- 20153504
TI  - The occurrence of persistent chlorinated and brominated organic contaminants in
      the European eel (Anguilla anguilla) in Irish waters.
AB  - The European eel (Anguilla anguilla) is a relatively high lipid, long lived
      species capable of living in a variety of brackish, fresh and marine habitats. As
      such, eels can accumulate organic pollutants and have been incorporated into
      environmental monitoring programs as a suitable "bioindicator" species for the
      determination of the levels of organic contaminants within different water
      bodies. The global eel stock is now in decline and while the cause of the
      collapse remains unidentified, it is likely to include a combination of
      anthropogenic mortality in addition to environmental degradation. This study
      provides valuable data on a range of contaminants (PCDD/Fs, PCBs, OCPs, PBDEs,
      HBCD, TBBPA and PBBs) and extractable lipid levels in eel muscle tissue collected
      from five Irish catchments. Extractable lipid levels were lower in the yellow
      eels compared to those in the silver eels. These levels were similar to those
      reported elsewhere and it has been posited that a decline in the lipid content in
      yellow eels may have consequences for the future viability of the stock. With the
      exception of higher substituted dioxins (especially OCDD), in three samples
      collected from one catchment (Burrishoole) in the West of Ireland, POP levels in
      general were determined to be low in eels from Irish waters compared to those in
      other countries.

PMID- 20153505
TI  - JAK2 V617F mutation is uncommon in patients with the 3q21q26 syndrome.
AB  - The 3q21q26 syndrome is recognized as a distinct clinicopathologic entity.
      Patients have a myeloid neoplasm associated with 3q21q26 cytogenetic
      abnormalities and present with anemia, leukopenia, and either thrombocytosis or a
      normal platelet count associated with dysplasia. To determine if JAK2 V617F
      mutation is implicated in the abnormal thrombopoiesis of the 3q21q26 syndrome, we
      analyzed bone marrow samples of 12 patients, including 10 patients with acute
      myeloid leukemia and 2 patients with a myelodysplastic syndrome, associated with
      either inv(3)(q21;q26) or t(3;3)(q21;q26). The platelet count ranged from 142 to
      597 x 10(3)/microL. Using polymerase chain reaction and pyrosequencing assays, no
      evidence of JAK2 V617F was identified in 11 of 12 cases. A JAK2 V617F mutation
      was identified in one patient who had acute myeloid leukemia with concurrent mast
      cell disease. Separate DNA analysis of myeloblasts and mast cells after laser
      capture microdissection confirmed that JAK2 V617F was present in both components.
      We conclude that JAK2 V617F mutation is uncommon in the 3q21q26 syndrome and that
      its presence may indicate an unusual coexistence of a myeloproliferative
      neoplasm.

PMID- 20153506
TI  - S100P is a novel marker to identify intraductal papillary mucinous neoplasms.
AB  - Intraductal papillary mucinous neoplasms of the pancreas are subclassified based
      on morphological features, and different immunohistochemical profiles have been
      identified in association with the subtypes. We previously reported that S100P
      was an early developmental marker of pancreatic carcinogenesis and that there was
      higher S100P expression in intraductal papillary mucinous neoplasms than in
      normal pancreatic ductal epithelium. However, there have been no reports on novel
      diagnostic markers to distinguish intraductal papillary mucinous neoplasm from
      nonneoplastic lesions. Surgical specimens of intraductal papillary mucinous
      neoplasm obtained from 105 patients were investigated using immunohistochemistry.
      S100P expression was not detected in normal pancreatic ductal epithelium but was
      detected in all intraductal papillary mucinous neoplasm cells (100%) with diffuse
      nuclear or nuclear/cytoplasmic staining. MUC5AC was also expressed in most of the
      intraductal papillary mucinous neoplasms (102/105; 97%). Furthermore, S100P was
      clearly expressed in the invasive component of intraductal papillary mucinous
      neoplasms (32/32; 100%), including perineural and lymphatic and minimal invasion.
      On the other hand, MUC5AC was expressed in only 23 cases of 32 invasive
      components (P < .01). These data suggest that the S100P antibody may be a useful
      marker for detecting all types of intraductal papillary mucinous neoplasms.

PMID- 20153508
TI  - Mediastinal germ cell tumors with an angiosarcomatous component: a report of 12
      cases.
AB  - The development of an angiosarcomatous component in germ cell tumors is rare.
      Here we studied 12 cases of mediastinal germ cell tumors with an angiosarcomatous
      component. All patients were men with a mean age of 34 years (range, 24-49
      years). No patient had a documented testicular germ cell tumor. The mean size of
      mediastinal tumors was 12.9 cm (range, 5.5-16.0 cm). Grossly, the tumors were
      cystic with variegated hemorrhagic, mucinous, and fleshy solid areas.
      Microscopically, all tumors were composed of germ cell tumor. The most common
      germ cell tumor component was teratoma (n = 10); and other germ cell tumor
      components included seminoma (n = 3), yolk sac tumor (n = 3), embryonal carcinoma
      (n = 2), and choriocarcinoma (n = 1). The angiosarcomatous component was present
      in primary mediastinal tumors (n = 6), metastasis (n = 3), or both primary
      mediastinal tumor and metastasis (n = 3). The angiosarcomatous component
      accounted for an average of 30% (range, 5%-95%) of the primary mediastinal tumor.
      In addition, other non-germ cell components, including rhabdomyosarcoma (n = 3),
      leiomyosarcoma (n = 1), and poorly differentiated carcinoma (n = 1), were also
      present in the tumors. Of the 10 patients with follow-up available, all patients
      developed metastasis (n = 8) or local recurrence (n = 2); 7 died of disease at a
      mean of 33 months (range, 21-75 months), and 3 patients were alive at a mean of
      75 months (range, 5-120 months). Our findings suggest that the presence of an
      angiosarcomatous component in mediastinal germ cell tumor, even in a small
      amount, is associated with a poor clinical outcome.

PMID- 20153509
TI  - Clinicopathologic study of 53 metaplastic breast carcinomas: their elements and
      prognostic implications.
AB  - Metaplastic carcinoma of the breast is a relatively rare cancer and includes
      various histologic types. In this cancer, metaplastic elements are heterogeneous
      and sometimes mixed. We investigated, by histopathologic means, these elements
      and clinical implications that could indicate the clinical course (including the
      prognosis). Fifty-three metaplastic breast carcinoma cases and their prognoses
      were investigated by initially examining the presence or absence of spindle-cell
      elements, and then the presence or absence of other elements. Spindle cells were
      classified as high or low grade. The number of spindle-cell-positive cases was 24
      (45%) of 53. The 24 spindle-cell (+) cases were subdivided into 12 high-grade
      (HGsp) (distant metastatic rate per 100 person-years, 13.27) and 12 low-grade
      (LGsp) (0.00) patients. Spindle-cell (-) cases were subdivided into 22 pure
      squamous cell carcinomas (5.93) and 7 matrix-producing carcinomas (0.00). There
      were significant differences among the 4 groups with regard to the disease-free
      period (P = .0081, log-rank test). The distant metastatic risks in the HGsp and
      pure squamous cell carcinomas groups were significantly higher than that in the
      matrix-producing carcinoma + LGsp group (nonmetastatic groups) after controlling
      for the effects of tumor size and lymph node metastasis (P = .019 and P = .016,
      respectively, Poisson regression model). The presence of high-grade spindle cells
      was related to the prognosis, and some histologic subtypes may be important with
      respect to the prognosis. The presence of high-grade spindle cells in metaplastic
      breast carcinoma may indicate aggressive behavior.

PMID- 20153510
TI  - Candida albicans-associated necrotizing vasculitis producing life-threatening
      gastrointestinal hemorrhage.
AB  - Patients undergoing treatment of acute lymphoblastic leukemia are at risk for
      fungal infections including disseminated candidiasis. We describe a case of
      systemic Candida albicans infection associated with life-threatening
      gastrointestinal hemorrhage due to unusual necrotizing vasculitis involving the
      gastrointestinal tract. We explore the association between Candida and such
      vasculopathy.

PMID- 20153511
TI  - Mixed infection of Trypanosoma cruzi I and II in a Colombian cardiomyopathic
      patient.
AB  - The Trypanosoma cruzi taxon is composed of 2 major lineages, T cruzi I and T
      cruzi II. The clinical symptoms of Chagas disease are highly variable, and their
      geographic distribution is correlated with the distribution of the parasite
      lineages. In Colombia and northern South America, T cruzi I lineage is associated
      with chagasic cardiomyopathy. Alternatively, in the countries south cone of South
      America, there is a predominance of T cruzi II, which is associated with
      cardiomyopathy and digestive diseases. We report for the first time a mixed
      infection consisting of both T cruzi I and T cruzi II detected in the esophagus
      and in the heart, respectively, of a cardiomyopathic patient from an endemic area
      in Santander, Colombia. This finding has epidemiological relevance related to the
      association of T cruzi II with the clinical manifestations of Chagas disease and
      its frequency in Colombia and countries in northern South America.

PMID- 20153513
TI  - Infantile hemangioendothelioma with elevated serum alpha fetoprotein: report of 2
      cases with immunohistochemical analysis.
AB  - Infantile hemangioendothelioma is the most common benign mesenchymal tumor of the
      liver presenting during the first 6 months of life. Serum alpha fetoprotein is an
      important tumor marker for hepatoblastoma, hepatocellular carcinoma, and germ
      cell tumors. However, it is rarely elevated in patients with hepatic infantile
      hemangioendothelioma. In such cases, surgery may be done to rule out malignancies
      when alpha fetoprotein levels are high. The etiology of the elevated alpha
      fetoprotein level has not yet been elucidated. We report 2 cases of solitary
      hepatic infantile hemangioendothelioma and demonstrate immunohistochemically that
      hepatocytes near or entrapped within the tumor were the source of the increased
      serum levels of alpha fetoprotein explaining the unusual clinical presentation.

PMID- 20153512
TI  - Mammalian target of rapamycin is a biomarker of poor survival in metastatic
      serous ovarian carcinoma.
AB  - The AKT signaling pathway is crucial for cancer cell survival. The objective of
      this study was to analyze the expression and clinical role of this pathway in
      serous ovarian carcinoma. Phospho-AKT and phospho-mammalian target of rapamycin
      protein expression was studied in 269 ovarian carcinomas (159 effusions, 38
      primary carcinomas, 72 solid metastases) using immunohistochemistry. The
      association between AKT, mammalian target of rapamycin, and DJ-1 in effusions was
      quantitatively analyzed using flow cytometry. AKT phosphorylation status in
      effusions was further studied using Western blotting. Phospho-AKT and phospho
      mammalian target of rapamycin were detected in the majority of tumors at all
      anatomical sites. Phospho-AKT expression in effusions was higher in grade 3
      versus grades 1 and 2 tumors (P = .013). Flow cytometry analysis showed
      association between AKT, mammalian target of rapamycin, and DJ-1 expression (P <
      .001). Higher phospho-AKT Thr308/pan-AKT ratio by Western blotting was associated
      with more advanced International Federation of Gynecology and Obstetrics stage (P
      = .018) and a trend for poor response to chemotherapy at first disease recurrence
      (P = .051). Higher phospho-mammalian target of rapamycin protein expression in
      effusions by immunohistochemistry was associated with poor progression-free
      survival for patients with postchemotherapy effusions (P = .005). Phospho
      mammalian target of rapamycin was an independent predictor of poor progression
      free survival for patients with postchemotherapy effusions (P = .03). The
      association between activated AKT and mammalian target of rapamycin expression
      and clinicopathologic parameters of aggressive disease, including shorter patient
      survival, provides further evidence regarding the central role of this signaling
      pathway in ovarian carcinoma.

PMID- 20153514
TI  - Ryegrass uptake of carbamazepine and ibuprofen applied by urine fertilization.
AB  - Human urine is a potential alternative fertilizer for agriculture. However, its
      usage is associated with a risk of spreading pharmaceutical residues to fields.
      The individual and combined behavior of carbamazepine and ibuprofen was
      investigated by GC/MS analysis in a greenhouse experiment using ryegrass
      fertilized with pharmaceutical-spiked urine. Only carbamazepine could be detected
      in soil, roots, and aerial plant parts. Fifty-three per cent of carbamazepine
      originally present in the urine was recovered in soil samples taken after three
      months. Additionally, 34% of carbamazepine was found in aerial plant parts and
      0.3% in roots. Model calculations showed that neither roots nor Casparian strip
      posed a considerable barrier to uptake. Carbamazepine transport was clearly
      driven by transpiration. Ibuprofen was not detected in the soil or in any plant
      parts after three months. This was assumed to be due to biodegradation of
      ibuprofen. Carbamazepine and ibuprofen, singly or in combination, did not
      adversely affect the growth of ryegrass.

PMID- 20153515
TI  - Formation of procoagulant microparticles and properties.
AB  - The platelet procoagulant response consists of providing a catalytic surface
      where vitamin K-dependent clotting factors can interact with cofactors to form
      the characteristic enzyme complexes of the cascade culminating in the generation
      of sufficient thrombin for effective hemostasis. The essential element allowing
      such a local concentration is the anionic aminophospholipid phosphatidylserine,
      sequestered in the inner leaflet of the plasma membrane of resting cells but
      swiftly translocated to the outer leaflet after stimulation. Phosphatidylserine
      egress is followed by the shedding of membrane fragments, the so-called
      microparticles or microvesicles, also endowed with procoagulant properties more
      particularly when they harbor tissue factor, the major initiator of blood
      coagulation reactions. Furthermore, because microparticles hijack a number of
      membrane and cytoplasmic components from the cells they derive, they can elicit
      various responses in proximal or remote cells they interact with and can
      therefore be viewed as intercellular "macromessengers". Although several
      regulatory mechanisms have been proposed, the main actors responsible for the
      whole process of phosphatidylserine transmembrane redistribution and subsequent
      microparticle release remain to be identified.

PMID- 20153516
TI  - Hydroxyapatite nanorods as novel fillers for improving the properties of dental
      adhesives: Synthesis and application.
AB  - OBJECTIVES: This study evaluates the hypothesis that the incorporation of fibrous
      hydroxyapatite nanoparticles with high crystallinity and high aspect ratio,
      synthesized by hydrothermal method, into an experimental ethanol-based one-bottle
      dentin adhesive, improves the mechanical properties of the adhesive layer, and
      accordingly increases the bond strength to dentin. METHODS: Hydroxyapatite
      nanorods were synthesized using a simple hydrothermal procedure. First, the
      HPO(4)(2)-containing solution was added drop-wise into the Ca(2+)-containing
      solution while the molar ratio of Ca/P was adjusted at 1.67. The HAp precursor
      was then treated hydrothermally at 200 degrees C for 60h. The resulting powder
      was characterized using XRD, FTIR, SEM, TEM, and EDXA. The synthesized HAp
      nanorods were added to an experimental one-bottle dentin adhesive followed by the
      characterization of the filled adhesive. The diametral tensile strength, flexural
      strength, flexural modulus, and the microshear bond strength to the dentin of
      human premolars of seven adhesive systems containing different nanorod contents
      were evaluated. The distribution of the filler was determined using EDX-mapping.
      The depth of cure was also evaluated using scraping technique. Moreover, after
      microshear testing, the fracture cross-section was observed using SEM to
      determine the mode of failure involved. The colloidal stability was studied using
      a separation analyzer and also zeta potential measurement. Data were analyzed
      using one-way analysis of variance followed by the Tukey test. RESULTS: The
      results confirmed the high purity, high crystallinity, and high aspect ratio of
      synthesized HAp nanorods. The diametral tensile strength of nanorod containing
      adhesive system appeared to increase when 0.2-0.5wt.% HAp nanorods were
      incorporated (p<0.05). A similar trend was observed in the flexural test
      providing higher flexural strength at filler contents of 0.2-0.5wt.% while
      flexural modulus remained unchanged. The highest microshear bond strength was
      also obtained at 0.2wt.% filler content (p<0.05). The improved properties of the
      new adhesive system might be due to the high crystallinity and high aspect ratio
      of the nanorods. SEM observation of debonded surfaces revealed that most
      specimens showed an adhesive failure from the adhesive-dentin interface. Energy
      dispersive X-ray (EDX) mapping confirmed the uniform distribution of nanorods in
      the adhesive matrix. The colloidal stability studies indicated that synthesized
      hydroxyapatite nanorods have high colloidal stability in the dental adhesive
      solution. Indeed, the nanorods are well dispersed and protected from aggregation
      by their high surface charge confirmed by zeta potential measurement.
      SIGNIFICANCE: Hydroxyapatite-based composites have shown promising bioactivity.
      However, the knowledge about the influence of the nano-sized HAp on the
      properties of the dental materials, especially dentin bonding adhesives, is yet
      insufficient. The nanorod containing adhesive system presented here might be
      considered to have practical applications in dental clinics.

PMID- 20153517
TI  - Factors that influence the accuracy of adolescent proxy reporting of parental
      characteristics: a research note.
AB  - Socioeconomic status (SES) is considered to be an important marker of physical,
      mental, and social outcomes. However, methods used to gather socioeconomic
      information vary widely in terms of both the indicators of SES used (e.g.,
      education, occupation, income, etc.) and data collection strategies. In
      particular, studies of adolescents often rely on children's proxy reports of
      measures of parents' SES. There is disagreement in the literature regarding
      children's ability to reliably serve as proxy respondents for their parents.
      Using data from the National Longitudinal Study of Adolescent Health, a
      nationally representative sample of adolescents and their parents, we assess the
      accuracy of children's proxy reports of mothers' education and receipt of public
      assistance. Results show that accuracy of children's proxy reports varies by
      children's age, gender, and race; however, social class largely accounts for race
      differences found.

PMID- 20153518
TI  - Psychosocial working conditions, school sense of coherence and subjective health
      complaints. A multilevel analysis of ninth grade pupils in the Stockholm area.
AB  - This study explores the psychosocial working conditions of 7930 Swedish 9th grade
      students, distributed over 475 classes and 130 schools, in relation to their
      subjective health using multilevel modeling. At the individual level, students
      with "strained" working conditions in school (i.e. those experiencing a high
      level of demands in combination with a low level of control) demonstrated
      significantly worse health compared to students in "low-strain" situations.
      "Strained" conditions in combination with a weak school-related sense of
      coherence were especially unfavourable for health. These findings remained
      significant when support from teachers, school marks, norm-breaking behaviours,
      family-relations and certain class- and school-contextual conditions were
      adjusted for. Thus, while demands are an essential part of school work, this
      study suggests that high levels of control and a strong school-related sense of
      coherence can protect against the more detrimental effects on health that high
      demands at school may cause.

PMID- 20153519
TI  - Health effects of hot weather: from awareness of risk factors to effective health
      protection.
AB  - Because of the increasing concerns about climate change and deadly heatwaves in
      the past, the health effects of hot weather are fast becoming a global public
      health challenge for the 21st century. Some cities across the world have
      introduced public health protection measures, with the timely provision of
      appropriate home-based prevention advice to the general public being the most
      crucial point of intervention. In this Review, we report current epidemiological
      and physiological evidence about the range of health effects associated with hot
      weather, and draw attention to the interplay between climate factors, human
      susceptibility, and adaptation measures that contribute to heat burdens. We focus
      on the evidence base for the most commonly provided heat-protection advice, and
      make recommendations about the optimum clinical and public health practice that
      are expected to reduce health problems associated with current and future hot
      weather.

PMID- 20153520
TI  - An cell-assembly derived physiological 3D model of the metabolic syndrome, based
      on adipose-derived stromal cells and a gelatin/alginate/fibrinogen matrix.
AB  - One of the major obstacles in drug discovery is the lack of in vitro three
      dimensional (3D) models that can capture more complex features of a disease.Here
      we established a in vitro physiological model of the metabolic syndrome (MS)
      using cell-assembly technique (CAT), which can assemble cells into designated
      places to form complex 3D structures. Adipose-derived stromal (ADS) cells were
      assembled with gelatin/alginate/fibrinogen. Fibrin was employed as an effective
      material to regulate ADS cell differentiation and self-organization along with
      other methods. ADS cells differentiated into adipocytes and endothelial cells,
      meanwhile, the cells were induced to self-organize into an analogous tissue
      structure. Pancreatic islets were then deposited at designated locations and
      constituted the adipoinsular axis with adipocytes. Analysis of the factors
      involved in energy metabolism showed that this system could capture more
      pathological features of MS. Drugs known to have effects on MS showed accordant
      effects in this system, indicating that the model has potential in MS drug
      discovery. Overall, this study demonstrated that cell differentiation and self
      organization can be regulated by techniques combined with CAT. The model
      presented could result in a better understanding of the pathogenesis of MS and
      the development of new technologies for drug discovery.

PMID- 20153522
TI  - Enhancing in vivo vascularized bone formation by cobalt chloride-treated bone
      marrow stromal cells in a tissue engineered periosteum model.
AB  - The periosteum plays an indispensable role in both bone formation and bone defect
      healing. In this study we constructed an artificial in vitro periosteum by
      incorporating osteogenic differentiated bone marrow stromal cells (BMSCs) and
      cobalt chloride (CoCl(2))-treated BMSCs. The engineered periostea were implanted
      both subcutaneously and into skull bone defects in SCID mice to investigate
      ectopic and orthotopic osteogenesis and vascularization. After two weeks in
      subcutaneous and four weeks in bone defect areas, the implanted constructs were
      assessed for ectopic and orthotopic osteogenesis and vascularization by micro-CT,
      histomorphometrical and immunohistochemical methods. The results showed that
      CoCl(2) pre-treated BMSCs induced higher degree of vascularization and enhanced
      osteogenesis within the implants in both ectopic and orthotopic areas. This study
      provided a novel approach using BMSCs sourced from the same patient for both
      osteogenic and pro-angiogenic purposes in constructing tissue engineered
      periosteum to enhance vascularized osteogenesis.

PMID- 20153521
TI  - The enhanced characteristics of osteoblast adhesion to photofunctionalized
      nanoscale TiO2 layers on biomaterials surfaces.
AB  - Recently, UV photofunctionalization of titanium has been shown to be effective in
      enhancing osteogenic environment around this functional surface, in particular
      for the use of endosseous implants. However, the underlying mechanism remains
      unknown and its potential application to other tissue engineering materials has
      never been explored. We determined whether adhesion of a single osteoblast is
      enhanced on UV-treated nano-thin TiO(2) layer with virtually no surface roughness
      or topographical features. Rat bone marrow-derived osteoblasts were cultured on
      UV-treated or untreated 200-nm thick TiO(2) sputter-coated glass plates. After an
      incubation of 3 h, the mean critical shear force required to initiate detachment
      of a single osteoblast was determined to be 1280 +/- 430 nN on UV-treated TiO(2)
      surfaces, which was 2.5-fold greater than the force required on untreated TiO(2)
      surfaces. The total energy required to complete the detachment was 37.0 +/- 23.2
      pJ on UV-treated surfaces, 3.5-fold greater than that required on untreated
      surfaces. Such substantial increases in single cell adhesion were also observed
      for osteoblasts cultured for 24 h. Osteoblasts on UV-treated TiO(2) surfaces were
      larger and characterized with increased levels of vinculin expression and focal
      contact formation. However, the density of vinculin or focal contact was not
      influenced by UV treatment. In contrast, both total expression and density of
      actin fibers increased on UV-treated surfaces. Thin layer TiO(2) coating and UV
      treatment of Co-Cr alloy and PTFE membrane synergistically resulted in a
      significant increase in the ability of cell attachment and osteoblastic
      production of alkaline phosphatase. These results indicated that the adhesive
      nature of a single osteoblast is substantially enhanced on UV-treated TiO(2)
      surfaces, providing the first evidence showing that each individual cell attached
      to these surfaces is substantially more resistant to exogenous load potentially
      from blood and fluid flow and mechanical force in the initial stage of in vivo
      biological environment. This enhanced osteoblast adhesion was supported
      synergistically but disproportionately by enhancement in focal adhesion and
      cytoskeletal developments. Also, this study demonstrated that UV treatment is
      effective on nano-thin TiO(2) depositioned onto non-Ti materials to enhance their
      bioactivity, providing a basis for TiO(2)-mediated photofunctionalization of
      biomaterials, a new method of developing functional biomaterials.

PMID- 20153523
TI  - The effect of grafted methoxypoly(ethylene glycol) chain length on the inhibition
      of respiratory syncytial virus (RSV) infection and proliferation.
AB  - Respiratory syncytial virus (RSV) is a significant cause of morbidity in humans.
      To date, no effective treatments exist and current prophylactic therapy access is
      limited and is only approximately 50% effective. To attenuate the risk of RSV
      infection, we hypothesized that bioengineering of either the virus particle or
      host cell via the covalent grafting of methoxypoly(ethylene glycol) [mPEG] would
      prevent infection. To this end, the anti-viral effects of grafting concentration,
      linker chemistry and polymer length on RSV infection was assessed. For viral
      modification, short chain polymers (2 kDa) were significantly more effective than
      long chain (20 kDa) polymers. In contrast, modification of host cells with small
      polymers provided no (approximately 0%) protection while long chain polymers
      effectively prevented infection. For example, at 48 hours post-infection at a
      multiplicity of infection of 0.5 and grafting concentrations of 5, 7.5, and 15
      mm, 20 kDa mPEG decreased infection by 45, 83, and 91%, respectively.
      Importantly, both viral and host cell PEGylation strategies were able to provide
      near complete protection against RSV infection of both non-polarized and
      polarized cells. In conclusion, mPEG-modification of either RSV or the host cell
      is a highly effective prophylactic strategy for preventing viral infection.

PMID- 20153524
TI  - The behaviour of neural stem cells on polyhydroxyalkanoate nanofiber scaffolds.
AB  - Polyhydroxyalkanoates (PHA) have demonstrated their potentials as medical implant
      biomaterials. Neural stem cells (NSCs) grown on/in PHA scaffolds may be useful
      for repairing central nervous system (CNS) injury. To investigate this
      possibility, nanofiber matrices (scaffolds) prepared from several PHA via a novel
      phase separation process were studied to mimic natural extracellular matrix
      (ECM), and rat-derived NSCs grown in the PHA matrices were characterized
      regarding their in vitro differentiation behaviors. All three PHA materials
      including poly(3-hydroxybutyrate) (PHB), copolymer of 3-hydroxybutyrate and 4
      hydroxybutyrate (P3HB4HB), and copolymer of 3-hydroxybutyrate and 3
      hydroxyhexanoate (PHBHHx) supported NSC growth and differentiation both on their
      2D films and 3D matrices. Among three PHA nanofiber matrices, PHBHHx one showed
      the strongest potentials to promote NSC differentiation into neurons which is
      beneficial for CNS repair. Compared to the 2D films, 3D nanofiber matrices
      appeared to be more suitable for NSC attachment, synaptic outgrowth and
      synaptogenesis. It was suggested that PHBHHx nanofiber scaffolds (matrices) that
      promote NSC growth and differentiation, can be developed for treating central
      nervous system injury.

PMID- 20153525
TI  - Potent in vitro chondrogenesis of CD105 enriched human adipose-derived stem
      cells.
AB  - Adipose-derived stem cells (ASCs) are considered as a promising cell source for
      cartilage regeneration. However, the heterogeneity of this cell source may affect
      their ability in cartilage formation. It is therefore necessary to establish an
      efficient method for isolating the cells that have chondrogenic potential. To
      date, no specific markers have been reported to be able to isolate such a cell
      population from human adipose tissue. In recent studies, endoglin (CD105) has
      been known as a relatively specific marker for identifying mesenchymal stem
      cells, but no studies show it is related to chondrogenic potential of human ASCs.
      In this study, human cells from adipose tissue were isolated, cultured, and
      sorted according to CD105 expression. The sorted cells were then subjected to
      adipogenic, osteogenic, and chondrogenic induction to confirm their multi
      potentiality. In adipogenic conditions, CD105- cells showed stronger Oil Red
      staining and higher expression of adipose-specific genes compared to CD105+
      cells. By contrast, CD105+ cells exhibited better osteogenic potential with
      stronger Alizarin Red staining and higher expression of osteogenic specific genes
      than CD105- cells. Noticeably, CD105+ cells also exhibited a much stronger
      chondrogenic potential than CD105- cells, with stronger collagen II staining and
      higher gene expression of collagen II and aggrecan. Most importantly, CD105+
      cells could form a homogeneous cartilage-like tissue when seeded into a
      biodegradable scaffold and cultured in chondrogenic media for 8 weeks. These
      results indicate that sorting of ASC subpopulation with CD105 as a marker may
      allow better in vitro chondrogenesis and thus provide an important implications
      for cartilage regeneration and reconstruction using autologous cells from adipose
      tissue.

PMID- 20153526
TI  - Sustained clinical remission despite suboptimal molecular response to imatinib in
      e1a2 BCR-ABL chronic myeloid leukemia.

PMID- 20153527
TI  - Who spares the rod? Religious orientation, social conformity, and child abuse
      potential.
AB  - OBJECTIVE: Relatively little research has investigated the connection between
      religiosity and physical child abuse risk. Certain aspects, such as specific
      religious orientation or beliefs, and cognitive schema, such as socially
      conformist beliefs, may account for the connection that some have claimed
      increase religious parents' abuse potential. The current study examined whether
      greater Extrinsic religiosity, but not Intrinsic religiosity, was associated with
      elevated physical abuse potential. Those who hold a literal interpretation of the
      Bible and attend church more frequently were also expected to evidence increased
      abuse risk. Additionally, the role of social conformity in mediating or
      moderating the association between religiosity and abuse potential was
      investigated. METHODS: Two hundred and seven regularly attending Christians of
      various denominations completed self-report measures of religiosity, social
      conformity, and child abuse potential. RESULTS: Findings indicate that Extrinsic
      religiosity was associated with increased physical abuse potential, with greater
      social conformity further moderating this association. Intrinsic religious
      orientation was not associated with abuse risk. Further, those who consider the
      Bible to be literally true were more socially conformist and evidenced greater
      abuse risk. CONCLUSIONS: For those working with religious parents, the particular
      nature of religiosity needs to be considered when interpreting a connection
      between religiosity and abuse risk, as well as the potential attitudes the parent
      holds regarding the need for conformity. Given the complexity of religiosity,
      future research should explore other potential mediating and moderating factors
      that could further clarify its connection to physical abuse risk. PRACTICE
      IMPLICATIONS: Clarifying how religiosity relates to child abuse risk has
      implications for professionals working with the vast numbers of parents for whom
      religion is a visible force in their daily lives. Findings from the present study
      suggest that professionals should consider the underlying motivation for an
      individual's religion as well as the importance the individual places on
      conformity. Religiosity per se may not be as critical to predicting physical
      abuse risk as selected approaches to religion or particular attitudes the
      religious individual assumes in their daily life.

PMID- 20153529
TI  - Complexes with anti-epitope tag IgGs improve the therapeutic potential of epitope
      tagged antibody fragments.
AB  - The use of recombinant antibody fragments (rAbF) as therapeutic agents is
      compromised by shorter serum persistences than IgG therapeutics and their
      inability to mediate Fc-dependent effector functions. Here, we show that the
      strategy of complex formation between epitope-tagged rAbFs and anti-epitope IgG
      monoclonal antibodies (mAb) can improve the therapeutic potential of rAbFs by
      both enhancing their serum persistence and conferring on them the ability to
      recruit Fc-mediated effector functions. These two mechanistic aspects of this
      strategy were demonstrated using c-myc- and 6xHis-tagged Fab and scFv rAbFs, both
      directed against Pseudomonas aeruginosa O6ad, in combination with two different
      murine anti-epitope tag IgGs, anti-5xHis IgG (Penta-His) and anti-c-myc IgG
      (9E10). Further enhancement of this strategy for the employment of rAbFs as
      therapeutics is discussed.

PMID- 20153531
TI  - Re: migratory foreign body of neck in a battered baby: a case report.

PMID- 20153530
TI  - Topology of the membrane-bound form of complement protein C9 probed by
      glycosylation mapping, anti-peptide antibody binding, and disulfide modification.
AB  - The two N-linked oligosaccharides in native human C9 were deleted by site
      specific mutagenesis. This aglycosyl-C9 did not differ from its native form in
      hemolytic and bactericidal activity. A new N-glycosylation site (K311N/E313T) was
      introduced into the turn of a helix-turn-helix [HTH] fold that had been
      postulated to form a transmembrane hairpin in membrane-bound C9. This
      glycosylated form of human C9 was as active as the native protein suggesting that
      the glycan chain remains on the external side of the membrane and that
      translocation of this hairpin is not required for membrane anchoring.
      Furthermore, flow cytometry provided evidence for the recognition of membrane
      bound C9 on complement-lysed ghosts by an antibody specific for the HTH fold. A
      new N-glycosylation site (P26N) was also introduced close to the N-terminus of C9
      to test whether this region was involved in C9 polymerization, which is thought
      to be required for cytolytic activity of C9. Again, this glycosylated C9 was as
      active as native C9 and could be induced to polymerize by heating or incubation
      with metal ions. The two C-terminal cystines within the MACPF domain could be
      eliminated partially or completely without affecting the hemolytic activity. Free
      sulfhydryl groups of unpaired cysteines in such C9 mutants are blocked since they
      could not be modified with SH-specific reagents. These results are discussed with
      respect to a recently proposed model that, on the basis of the MACPF structure in
      C8alpha, envisions membrane insertion of C9 to resemble the mechanism by which
      cholesterol-dependent cytolysins enter a membrane.

PMID- 20153532
TI  - Multiple sclerosis - candidate mechanisms underlying CNS atrophy.
AB  - Recently it has become clear that the neuronal compartment plays a more important
      role than previously thought in the pathology of multiple sclerosis. Apart from
      demyelination, neuronal pathology is apparently largely responsible for the brain
      atrophy that can be observed early on and throughout the course of the disease.
      The loss of axons and their neurons in the course of chronic neuroinflammation is
      a major factor determining long-term disability in patients. The actual steps
      leading from immune attack against the myelin sheath to neuronal damage are not
      yet fully clear. Here we review key findings about direct axonal damage
      processes, demyelination-related neuronal pathology and cell-body pathology, the
      major pathologic correlates that underlie brain atrophy in MS.

PMID- 20153533
TI  - Feeding mechanics as the basis for differential uptake of the neurotoxin domoic
      acid by oysters, Crassostrea virginica, and mussels, Mytilus edulis.
AB  - The neurotoxin domoic acid (DA), produced by diatoms Pseudo-nitzschia spp., is
      transferred to humans via consumption of contaminated bivalves. This study
      examines feeding mechanisms, namely reduced filtration, pre-ingestive rejection
      and poor absorption, that might explain the comparatively low DA levels commonly
      found in oysters during toxic Pseudo-nitzschia blooms. Clearance rate (CR),
      absorption efficiency (AE) of organic matter and selective rejection in
      pseudofeces of oysters (Crassostrea virginica) and mussels (Mytilus edulis) were
      investigated in relation to the DA levels accumulated during 2-wk, simultaneous
      exposure to toxic Pseudo-nitzschia multiseries. Effects of temperature and P.
      multiseries cell size were also tested to identify conditions, if any, under
      which oysters can accumulate unsafe DA levels. Oysters accumulated 3.0-7.5x less
      DA than mussels from a short-celled P. multiseries clone (length=24microm) at 12
      degrees C. This was related to the 7.4-8.5x lower CRs determined for oysters
      relative to mussels at this temperature. Exposure to a longer-celled P.
      multiseries clone (81microm) resulted in up to 70x lower toxin levels in oysters
      compared to mussels, which was attributed to differential feeding selectivity.
      Mussels were unable to discriminate between long- and short-celled P. multiseries
      clones from a mixed suspension, whereas oysters were previously shown to
      preferentially reject long cells (>70microm) in pseudofeces. Both bivalves
      selectively rejected P. multiseries cells from mixed suspensions containing a
      flagellate but not another diatom. AE of organics from P. multiseries cells by
      oysters and mussels was comparably low (42 and 39%, respectively) and thus
      unlikely to explain their differential DA accumulation. CR and DA uptake by
      oysters were negligible at <or=4 degrees C but increased with increasing
      temperature up to 18 degrees C, although mean DA levels barely attained the
      regulatory limit (20microg g(-1)) when oysters were exposed to long P.
      multiseries cells. The maximum DA levels accumulated by mussels (320microg g(-1))
      and oysters (44microg g(-1)) exposed to short P. multiseries cells in our study
      support the inter-specific differences in toxicity during Pseudo-nitzschia
      blooms, which are expected to be exacerbated at lower temperatures and when long
      cells or chains are dominant. Additionally, when alternate, non-diatom
      phytoplankton species are present, both bivalves can feed selectively and thus
      accumulate much lower DA levels than those predicted from their overall CRs. Our
      results provide support for the evaluation of species-specific management of DA
      contaminated shellfish and need to be considered in modeling DA toxin kinetics of
      the two target species.

PMID- 20153534
TI  - Social support and long-term mortality in the elderly: role of comorbidity.
AB  - Several studies have demonstrated a global increase in morbidity and mortality in
      elderly subjects with low social support or high comorbidity. However, the
      relationship between social support and comorbidity on long-term mortality in
      elderly people is not yet known. Thus, the present study was performed to
      evaluate the relationship between social support and comorbidity on 12-year
      mortality of elderly people. A random sample of 1288 subjects aged 65-95 years
      interviewed in 1992 was studied. Comorbidity by Charlson Comorbidity Index (CCI)
      score and Social Support by a scale in which total score ranges from 0 to 17,
      assigning to lowest social support the highest score, were evaluated. At 12-year
      follow-up, mortality progressively increase with low social support and
      comorbidity increasing (from 41.5% to 66.7% and from 41.2% to 68.3%,
      respectively; p<0.001). Moreover, low social support progressively increases with
      comorbidity increasing (and 12.4+/-2.5 to 14.3+/-2.6; p<0.001). Accordingly,
      multivariate analysis shows an increased mortality risk of 23% for each increase
      of tertile of social support scale (Hazard ratio=HR=1.23; 95% CI=1.01-1.51;
      p=0.045). Moreover, when the analysis was performed considering different degrees
      of comorbidity we found that social support level was predictive of mortality
      only in subjects with the highest comorbidity (HR=1.39; 95% CI=1.082-1.78;
      p=0.01). Thus, low social support is predictive of long-term mortality in the
      elderly. Moreover, the effect of social support on mortality increases in
      subjects with the highest comorbidity.

PMID- 20153535
TI  - Falls in the elderly of the Family Health Program.
AB  - This study aims to determine the factors that may be related to falls in the
      elderly assisted by the Family Health Program (FHP). Elderly individuals aged 60
      years or over, who were assisted by the FHP primary care system (n=2209),
      responded to a sociodemographic and health questionnaire. Mental health was
      evaluated using the Geriatric Depression Scale (GDS) and quality of life was
      assessed by the Medical Outcome Study Short-Form Health Survey (SF-36). In order
      to verify which independent variables affected the occurrence of falls, logistic
      regression analysis was performed. 27.1% of the sample reported one fall during
      the previous year, and 8.7% were recurrent fallers over the same period. The
      factors considered in the final model for falls were: age over 80 years-old,
      female gender, the presence of more than eight associated diseases, need for
      hospitalization during the previous year and appointments outside the FHP
      routine, hearing complaints, GDS score over 11 points, and emotional problems SF
      36 score between 25 and 74 points. The factors included in the final model for
      falls can be easily identified and properly overcome by FHP strategy. Patient
      falling history investigation should thus form part of the FHP team routine. This
      concern should be reinforced when it comes to women aged 80 years and over.

PMID- 20153536
TI  - Prevalence of Mycobacterium avium subsp. paratuberculosis infection in adult
      Danish non-dairy cattle sampled at slaughter.
AB  - A voluntary, risk-based control program for paratuberculosis in dairy herds was
      started in 2006 in Denmark. The program does not include non-dairy herds, and the
      occurrence of Mycobacterium avium subsp. paratuberculosis (MAP) in these herds is
      unknown. The objective of this study was to establish the prevalence of MAP
      infected adult non-dairy cattle in Denmark. Serum samples were collected between
      October, 2008 and January, 2009 from every 6th animal over 24 months of age, sent
      to slaughter to Danish slaughterhouses from non-dairy herds. The final sample
      included 2345 cattle of 13 different breeds, with the largest breed group being
      crossbreds (of unknown breeds) (30%) and three dairy breeds (Danish Holstein,
      Danish Jersey and Danish Red Cattle) comprising 27% of the samples. The serum
      samples were tested using a MAP specific antibody ELISA (IDScreen) and positives
      were defined as the sample-to-positive ratio greater than 0.60. Estimation of the
      breed-specific apparent prevalences, true prevalences (TP), and true prevalences
      with a random effect of breed was done in a Bayesian analysis. Information about
      test sensitivity and specificity were based on literature data and expert
      information. Regardless of the method of analysis, the estimated prevalences
      showed similar differences between breeds. The dairy breeds Danish Jersey, Danish
      Holstein and Danish Red Cattle were ranked highest (i.e. with highest prevalence)
      (TP medians: 13, 10, and 6, respectively). Combined, the dairy breeds had a
      significantly higher prevalence than the other breeds, median TP (dairy)=15.7%
      vs. median TP (non-dairy)=0.8%. For the individual non-dairy breeds, the median
      estimates were generally higher, illustrating the problems of ranking groups
      based on relatively small sample sizes.

PMID- 20153537
TI  - The effects of a sick pay reform on absence and on health-related outcomes.
AB  - We evaluate the effects of a reduction in sick pay from 100 to 80% of the wage.
      Unlike previous literature, apart from absence from work, we also consider
      effects on doctor/hospital visits and subjective health indicators. We also add
      to the literature by estimating both switch-on and switch-off effects, because
      the reform was repealed 2 years later. We find a 2-day reduction in the number of
      days of absence. Quantile regression reveals higher point estimates (both in
      absolute and relative terms) at higher quantiles, meaning that the reform
      predominantly reduced long durations of absence. In terms of health, the reform
      reduced the average number of days spent in hospital by almost half a day, but we
      cannot find robust evidence for negative effects on health outcomes or perceived
      liquidity constraints.

PMID- 20153538
TI  - The influence of environmental factors on growth and interactions between
      Embellisia allii and Fusarium oxysporum f. sp. cepae isolated from garlic.
AB  - Embellisia allii results in the formation of a bulb canker and black soot on the
      surface of different alliums and it has been frequently detected on garlic bulbs
      together with the spoilage fungus, Fusarium oxysporum f. sp. cepae, which causes
      bulb basal plate rot. In this study, the influence of water activity (a(w)) and
      temperature on mycelial growth of E. allii and F. oxysporum f. sp. cepae,
      conidial size and sporulation of E. allii, interactions between E. allii and F.
      oxysporum f. sp. cepae, Index of Dominance (I(D)), and in situ virulence on
      garlic were examined. Mycelial growth of E. allii was optimal (5.97 mm/day) at
      0.995 a(w) and 25 degrees C, slower at 30 degrees C. However, almost no growth
      occurred at 0.937 a(w)/30 degrees C. F. oxysporum f. sp. cepae grew faster than
      E. allii, (6.3-7.4mm/day) at 30 degrees C. Interactions between E. allii and F.
      oxysporum f. sp. cepae were influenced by a(w) and temperature. Sporulation of E.
      allii was more abundant on PDA than on MEA, especially at high a(w) (0.995) and
      low temperature (20 degrees C), but almost no sporulation occurred at 30 degrees
      C regardless of nutritional medium or a(w) level. The spore length of E. allii
      was longer on PDA than MEA, and was significantly influenced by water
      availability. F. oxysporum f. sp. cepae was competitive against E. allii and had
      a higher I(D) value in comparison with E. allii especially at a higher
      temperature (30 degrees C). In situ virulence tests showed that E. allii was
      weakly virulent on the garlic bulb cloves while that of F. oxysporum f. sp. cepae
      was highly dependent on a(w).

PMID- 20153539
TI  - Phage adsorption to Lactobacillus plantarum: influence of physiological and
      environmental factors.
AB  - Bacteriophage infection of lactic acid bacteria (LAB) constitutes one of the
      major problems in the dairy industry, causing economic losses and a constant risk
      of low quality and/or unsafe foods. The first step in the phage biology is the
      adsorption on the host cell surface. In a previous study, a remarkable thermal,
      chemical and photocatalytic resistance was demonstrated by four phages of
      Lactobacillus plantarum (ATCC 8014-B1, ATCC 8014-B2, FAGK1 and FAGK2). In the
      present work, these phages were used to characterize the adsorption process on L.
      plantarum ATCC 8014. Clearly, the characterization of this process could increase
      the possibilities of design useful strategies in order to prevent phage
      infections. The influence of Ca(2+), temperature, pH and physiological cell state
      on phage adsorption was investigated. Burst sizes of phages ATCC 8014-B1 and ATCC
      8014-B2 were 60 and 83 PFU/infective centre, respectively. The four phages
      exhibited a high infectivity even at pH 4 and pH 11. Calcium or magnesium ions
      were not indispensable for cell lysis and plaque formation, and more than 99% of
      phage particles were adsorbed either in the presence or absence of Ca(2+), after
      15 min at 37 degrees C. Phage adsorption was only partially affected at 50
      degrees C, while reached its maximum between 30 and 42 degrees C. The highest
      adsorption values (99.9%) were observed from pH 5 to 7, after 30 min at 37
      degrees C. Adsorption rates decreased after the thermal inactivation of cells,
      though, when 20 microg/ml of chloramphenicol was used, adsorption values were
      similar on treated and untreated cells. All these results showed that the
      adsorption process was only partially affected by a few conditions: thermally
      killed host cells, an incubation temperature of 50 degrees C and pH values of 9
      and 10. Nevertheless, and unfortunately, those conditions are not commonly
      applied during fermented food manufacturing, thus restricting highly the
      application of strategies currently available to reduce phage infections in
      industrial environments. This work also contributes to increase the currently
      knowledge on the biological aspects of L. plantarum bacteriophages.

PMID- 20153540
TI  - Antimicrobial action of the American cranberry constituents; phenolics,
      anthocyanins, and organic acids, against Escherichia coli O157:H7.
AB  - We investigated the antimicrobial effect of constituents of the American
      cranberry (Vaccinium macrocarpon); sugar plus organic acids, phenolics, and
      anthocyanins, against Escherichia coli O157:H7. Each fractional component was
      assayed over a 24-h period with 5-log initial inocula to determine the minimal
      inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and log
      CFU/ml reductions, at their native pH and neutral pH. Each fraction produced
      significant reductions (P<0.05) at the native pH: MICs for sugars plus organic,
      phenolics, and anthocyanins were 5.6/2.6 Brix/acid (citric acid equivalents)
      2.70g/L (gallic acid equivalent), and 14.80mg/L (cyanidin-3-glucoside
      equivalent), respectively. Sugars plus organic acids at native pH (3) produced a
      reduction below detectable limits (<1 log CFU/ml) compared to the control at 24h
      for 11.3/5.2 and 5.6/2.6 Brix/acid. Phenolics at native pH (4) produced
      reductions below detectable limits compared to the control at 24h and initial
      inocula for treatments of 5.40 and 2.70g/L. Anthocyanins at native pH (2)
      produced reductions below detectable limits for treatments of 29.15 and 14.80mg/L
      cyanidin-3-glucoside equivalents. Neutralized phenolics and anthocyanins had the
      same MIC and MBC as those at their native pH. Neutralized sugars plus organic
      acids did not inhibit bacterial growth compared to the control. Neutralized
      phenolics reduced bacteria below detectable limits in treatments of 5.40g/L and
      2.70g/L compared to the control. Neutralized anthocyanins reduced bacterial
      growth below detectable limits at the concentration of 29.15mg/L, but at
      14.80mg/L there was no significant reduction. Stationary-phase cells of E. coli
      O157:H7 were treated with 5% of each fraction in 0.8% NaCl for 20min and viewed
      under transmission electron microscopy. All fractions caused significant damage
      compared the control. Sugars plus organic acids caused visible osmotic stress,
      while phenolics and anthocyanins caused disintegration of the outer membrane.

PMID- 20153541
TI  - Detection and quantification of Aspergillus section Flavi spp. in stored peanuts
      by real-time PCR of nor-1 gene, and effects of storage conditions on aflatoxin
      production.
AB  - Aspergillus flavus and A. parasiticus are the main species from section Flavi
      responsible for aflatoxin accumulation in stored peanuts. A real-time PCR (RT
      PCR) system directed against the nor-1 gene of the aflatoxin biosynthetic pathway
      as target sequence was applied to monitor and quantify Aspergillus section Flavi
      population in peanuts. Kernels were conditioned at four water activity (a(W))
      levels and stored during a 4-month period. The quantification of fungal genomic
      DNA in naturally contaminated peanut samples was performed using TaqMan
      fluorescent probe technology. Sensitivity tests demonstrated that DNA amounts
      accounting for a single conidium of A. parasiticus RCP08300 can be detected. A
      standard curve relating nor-1 copy numbers to colony forming units (cfu) was
      constructed. Counts of species of Aspergillus section Flavi from unknown samples
      obtained by molecular and conventional count (CC) methodologies were compared. A
      correlation between cfu data obtained by RT-PCR and CC methods was observed
      (r=0.613; p<0.0001); and the former always showed values higher by 0.5-1 log
      units. A decrease of fungal density was observed throughout the storage period,
      regardless of the quantification methodology applied. Total aflatoxin levels
      ranging from 1.1 to 200.4 ng/g were registered in peanuts conditioned at the
      higher a(W) values (0.94-0.84 a(W)). The RT-PCR assay developed appears to be a
      promising tool in the prediction of potential aflatoxigenic risk in stored
      peanuts, even in case of low-level infections, and suitable for rapid, automated
      and high throughput analysis.

PMID- 20153542
TI  - Comparison of clinical-metabolic monitoring and outcomes and coronary risk status
      in people with type 2 diabetes from Australia, France and Latin America.
AB  - AIM: To compare clinical-metabolic monitoring and coronary risk status in people
      with type 2 diabetes from Australia, France and Latin America. METHODS:
      Retrospective analysis of data collected at primary care (except ANDIAB-
      secondary care) [corrected] matched for age, gender and disease duration.
      Measurements included participants' characteristics, performance frequency of
      clinical-metabolic process indicators, and percentage of clinical-metabolic
      outcomes at recommended target values. RESULTS: The weighted mean of the
      percentage of process performance was within 68 to 81%; that of outcomes at
      target dropped to 29 to 45%. Although statistically significant, differences
      among groups were far from those in healthcare budgets, and probably only of
      marginal clinical impact. The percentage of patients with low, slight or high
      coronary risk was similar in the three groups, with most people at high or very
      high risk. CONCLUSIONS: Despite the high difference in health per capita
      investment and system characteristics among countries, the study populations had
      striking similarities regarding the low percentage of participants who achieved
      cardiovascular risk factor and diabetes treatment goals. Therefore, differences
      in health budget and system characteristics would not be the main drivers in care
      quality. Diabetes education at every level and quality care registries would
      contribute to improve this situation and assess such improvement.

PMID- 20153543
TI  - The clinical and economic burden of non-adherence with oral bisphosphonates in
      osteoporotic patients.
AB  - OBJECTIVES: This study aims to estimate the clinical and economic burden of non
      adherence with oral bisphosphonates in osteoporotic patients and the potential
      cost-effectiveness of adherence-enhancing interventions. METHODS: A validated
      Markov microsimulation model estimated costs and outcomes (i.e. the number of
      fractures and the quality-adjusted life-year (QALY)) for three adherence
      scenarios: no treatment, real-world adherence and full adherence over 3 years.
      The real-world adherence scenario employed data from a published observational
      study. The incremental cost per QALY gained was estimated and compared across the
      three adherence scenarios. RESULTS: The number of fractures prevented and the
      QALY gain obtained at real-world adherence levels represented only 38.2% and
      40.7% of those expected with full adherence, respectively. The cost per QALY
      gained of real-world adherence compared with no treatment was estimated at euro
      10279, and full adherence was found to be cost-saving compared with real-world
      adherence. CONCLUSIONS: This study suggests that more than half of the potential
      clinical benefits from oral bisphosphonates in patients with osteoporosis are
      lost due to poor adherence with treatment. Depending on their cost, interventions
      with improved adherence to therapy have the potential to be an attractive use of
      resources.

PMID- 20153544
TI  - Global immunization policy making processes.
AB  - This paper reports the results of a global survey on the topic of national
      immunization policy development. Countries reported on actors involved, sources
      of evidence consulted, challenges faced and desired changes in their immunization
      policy development processes. Most countries had established or would like to
      establish a national Immunization Technical Advisory Group (ITAG). Countries
      reported using many sources of information; the most valued being those from the
      World Health Organization (WHO). Common challenges of immunization policy
      development reported include funding, capturing the epidemiology of disease and
      coordination of government and stakeholders.

PMID- 20153546
TI  - The gene encoding the catalytically inactive beta-amylase BAM4 involved in starch
      breakdown in Arabidopsis leaves is expressed preferentially in vascular tissues
      in source and sink organs.
AB  - Genetic studies in Arabidopsis thaliana have shown that two members of the beta
      amylase (BAM) family BAM3 and BAM4 are required for leaf starch breakdown at
      night. Both are plastid proteins and while BAM3 encodes an active BAM, BAM4 is
      not an active alpha-1,4-glucan hydrolase. To gain further insight into the
      possible function of BAM4 we constructed reporter genes using promoters for both
      BAM3 and BAM4 genes, driving beta-glucuronidase (GUS) and luciferase (LUC)
      expression in transgenic Arabidopsis plants. Both promoters directed expression
      in vascular tissue throughout the plant including cotyledons, leaves, petioles,
      stems, petals, siliques and roots. Tissue sections showed expression to be
      focused in phloem cells in stem and petiole. The BAM3 promoter was also expressed
      strongly throughout the photosynthetic tissues of leaves, sepals and siliques,
      whereas the BAM4 promoter was not. Conversely, the BAM4 promoter was active in
      root tip but the BAM3 promoter was not. To confirm these expression patterns and
      to compare with expression of other starch genes we carried-out RT-PCR analysis
      on RNA from vascular (replum) and non-vascular (valve) tissues of siliques. This
      confirmed that BAM4 expression together with RAM1 (BAM5) and GWD2 genes is
      stronger in the replum than the valve, whereas BAM3 is strong in both tissues.
      These results show that even though BAM3 and BAM4 genes apparently interact
      genetically in leaf starch metabolism, BAM4 is preferentially expressed in non
      photosynthetic vascular tissue, so revealing a potentially greater level of
      complexity in the control of starch breakdown than had previously been
      recognised.

PMID- 20153547
TI  - Economic healthcare costs of Clostridium difficile infection: a systematic
      review.
AB  - Clostridium difficile infection (CDI) is the leading cause of infectious
      diarrhoea in hospitalised patients. CDI increases patient healthcare costs due to
      extended hospitalisation, re-hospitalisation, laboratory tests and medications.
      However, the economic costs of CDI on healthcare systems remain uncertain. The
      purpose of this study was to perform a systematic review to summarise available
      studies aimed at defining the economic healthcare costs of CDI. We conducted a
      literature search for peer-reviewed studies that investigated costs associated
      with CDI (1980 to present). Thirteen studies met inclusion and exclusion
      criteria. CDI costs in 2008 US dollars were calculated using the consumer price
      index. The total and incremental costs for primary and recurrent CDI were
      estimated. Of the 13, 10 were from the USA and one each from Canada, UK, and
      Ireland. In US-based studies incremental cost estimates ranged from $2,871 to
      $4,846 per case for primary CDI and from $13,655 to $18,067 per case for
      recurrent CDI. US-based studies in special populations (subjects with irritable
      bowel disease, surgical inpatients, and patients treated in the intensive care
      unit) showed an incremental cost range from $6,242 to $90,664. Non-US-based
      studies showed an estimated incremental cost of $5,243 to $8,570 per case for
      primary CDI and $13,655 per case for recurrent CDI. Economic healthcare costs of
      CDI were high for primary and recurrent cases. The high cost associated with CDI
      justifies the use of additional resources for CDI prevention and control.

PMID- 20153549
TI  - Swine influenza (novel H1N1): algorithms and common sense.

PMID- 20153548
TI  - Epidemiology and clonality of multidrug-resistant Acinetobacter baumannii from a
      healthcare region in Hong Kong.
AB  - We assessed the risk factors and molecular epidemiology of multidrug-resistant
      Acinetobacter baumannii (MDR-AB) in Hong Kong. The patients were treated in five
      hospitals in a healthcare region during 2005-2006. We performed genomic
      identification by amplified rRNA gene restriction analysis (ARDRA) and
      investigated the existence of metallo-beta-lactamases and the clonality of
      representative MDR-AB strains by phenotypic and molecular methods. Forty-five
      subjects with MDR-AB were compared with 135 controls (patients with no MDR-AB).
      In the logistic regression, chronic wound (odds ratio: 29.5, 95% confidence
      interval: 8.1-107.2; P<0.001) was the only factor independently associated with
      MDR-AB colonisation or infection. ARDRA identified all 45 MDR-AB as genomic
      species 2TU. Pulsed-field gel electrophoresis clustered all except two isolates
      into two clonal types, designated HKU1 and HKU2 with 24 and 19 isolates,
      respectively. The main features of HKU1 strains were ST26, adeB type XII,
      positivity for bla(OxA-23-like) and bla(OxA-51-like) genes and high level
      resistance to carbapenems. Most HKU1 strains retained susceptibility to
      gentamicin, cotrimoxazole and minocycline. By contrast, HKU2 strains exhibited
      ST22, adeB type II, and were usually positive only for the bla(OxA-51-like) gene
      and resistant to gentamicin, cotrimoxazole and minocycline. Both clones were
      found to have disseminated widely. In conclusion, clonal expansion is playing
      major roles in the increase of MDR-AB in these hospitals in Hong Kong. The
      findings highlight the need to enhance infection control measures.

PMID- 20153550
TI  - Clean Hands for Life: results of a large, multicentre, multifaceted, social
      marketing hand-hygiene campaign.
AB  - A year-long multifaceted hand-hygiene campaign entitled Clean Hands for Life
      targeting individual, environmental and organisational factors that influence
      healthcare worker (HCW) hand-hygiene behaviour was implemented in 36 acute and
      long-term care facilities in Vancouver Coastal Health region. The campaign
      involved rotation of ten novel posters, two poster contests, and distribution of
      multiple promotional items. A social marketing approach was used to implement and
      monitor the effectiveness of the campaign. Evaluation included quality assurance
      surveys, staff surveys (baseline, mid- and post-campaign), and focus groups. A
      total of 141 poster contest submissions was received, 5452 staff surveys
      completed and 14 focus groups conducted. Overall knowledge of the importance of
      hand-hygiene and intention to clean hands was high at baseline. No significant
      differences were observed when mid- and post-campaign scores were compared to
      baseline. The majority (89.5%) of HCWs reported that they preferred soap and
      water over alcohol hand gel. A significant increase in the self-reported use of
      hand-hygiene products was observed particularly among HCWs not providing direct
      patient care. Barriers to hand-hygiene included inappropriate placement of sinks,
      traffic flow issues, inadequately stocked washrooms, workload and time
      constraints. Organisational support was visible throughout the campaign. The
      results showed that social marketing is an effective approach in engaging HCWs.
      Hand-hygiene campaigns that focus almost exclusively on increasing awareness
      among HCWs may not be as successful as multifaceted campaigns or campaigns that
      target identified barriers to hand-hygiene.

PMID- 20153551
TI  - Nosocomial swine influenza (H1N1) pneumonia: lessons learned from an illustrative
      case.
AB  - In the spring of 2009, our institution found itself at the epicentre of the
      "herald wave" of the swine influenza (H1N1) pandemic in New York. We were
      inundated with hundreds of patients exhibiting influenza-like illnesses (ILIs),
      presenting for rapid influenza A testing. During this pandemic, an infant with
      newly diagnosed acute lymphatic leukaemia (ALL) was admitted for induction
      chemotherapy. After being in hospital for a week, she developed high fever and
      shortness of breath, although her chest X-ray was clear. She was admitted to the
      paediatric intensive care unit (PICU) for mechanical ventilation. As we were in
      the midst of the pandemic, diagnosis of H1N1 pneumonia was considered and reverse
      transcription-polymerase chain reaction for H1N1 was positive. Contact
      investigation revealed that none of her family members/visitors had been in
      recent/close contact with anyone with ILI/H1N1. The investigation also revealed
      that paediatric healthcare staff, in contact with H1N1 patients, had rotated into
      PICU to care for the patient. Although no specific individual could be
      identified, it seems likely that H1N1 was transmitted to the patient by a
      healthcare worker who worked both in the paediatric ward and the PICU. This is
      the first known case of nosocomial paediatric transmission of H1N1 pneumonia.

PMID- 20153552
TI  - Four country healthcare-associated infection prevalence survey: pneumonia and
      lower respiratory tract infections.
AB  - In 2006, the Hospital Infection Society was funded by the respective health
      services in England, Wales, Northern Ireland and the Republic of Ireland to
      conduct a prevalence survey of healthcare-associated infection (HCAI). Here, we
      report the prevalence of pneumonia and lower respiratory tract infection other
      than pneumonia (LRTIOP) in these four countries. The prevalence of all HCAIs was
      7.59% (5743 out of 75 694). Nine hundred (15.7%) of these infections were
      pneumonia, and 402 (7.0%) were LRTIOP. The prevalence of both infections was
      higher for males than for females, and increased threefold from those aged <35 to
      those aged >85 years (P<0.001). At the time of the survey or in the preceding
      seven days, 23.7% and 18.2% of patients with pneumonia and LRTIOP, respectively,
      were mechanically ventilated compared to 5.2% of patients in the whole study
      population. Meticillin-resistant Staphylococcus aureus (MRSA) was the cause of
      pneumonia and LRTIOP in 7.6% and 18.1% of patients, respectively (P<0.001). More
      patients with LRTIOP (4.2%) had concurrent diarrhoea due to Clostridium difficile
      compared to patients with pneumonia (2.4%), but this did not reach statistical
      significance. Other HCAIs were present in 137 (15.2%) of patients with pneumonia
      and 66 (16.4%) of those with LRTIOP. The results suggest that reducing
      instrumentation, such as mechanical ventilation where possible, should help
      reduce infection. The higher prevalence of MRSA as a cause of LRTIOP suggests a
      lack of specificity in identifying the microbial cause and the association with
      C. difficile emphasises the need for better use of antibiotics.

PMID- 20153553
TI  - Impact of active surveillance on meticillin-resistant Staphylococcus aureus
      transmission and hospital resource utilisation.
AB  - The utility of active surveillance cultures (ASCs) for meticillin-resistant
      Staphylococcus aureus (MRSA) has been a controversial aspect of infection
      prevention. This prospective cohort study analyses the effect of ASCs for MRSA on
      hospital-acquired infections in a tertiary care hospital (hospital 1) and a
      community-based hospital (hospital 2). Both hospitals have high MRSA prevalence
      and are part of a large healthcare system in southeastern Michigan. Hospital
      acquired infections in the intensive care unit (ICU) and in the rest of the
      hospital were compared before and after the implementation of ASCs in the ICUs.
      Patients in hospital 1 with evidence of MRSA colonisation from ASCs were placed
      in contact isolation during their stay in the ICU; patients from hospital 2
      remained in contact isolation throughout their hospital stay. Prevalence of MRSA
      colonisation on admission to the ICU was 23% and 13% in hospitals 1 and 2,
      respectively. Average incidence of new colonisation during the study period was
      1.85 per 1000 patient-days and 3.47 per 1000 patient-days in hospitals 1 and 2,
      respectively. A decrease in ventilator-associated pneumonia (VAP) occurred in
      both hospitals, whereas decrease in hospital-wide nosocomial MRSA infection was
      demonstrated only in hospital 2. We conclude that, in addition to standard
      infection prevention initiatives, ASC with contact precautions can be effective
      in reducing the incidence of VAP and nosocomial MRSA infection in healthcare
      communities with endemic MRSA.

PMID- 20153554
TI  - Nasal meticillin-resistant Staphylococcus aureus carriage among intensive care
      unit hospitalised adult patients in a Taiwanese medical centre: one time-point
      prevalence, molecular characteristics and risk factors for carriage.
AB  - From 25 June to 11 July 2008, a total of 177 adult patients hospitalised in an
      intensive care unit (ICU) (94 in medical ICUs and 83 in surgical ICUs) at a
      tertiary care hospital were screened for nasal carriage of meticillin-resistant
      Staphylococcus aureus (MRSA) by polymerase chain reaction. The overall prevalence
      of S. aureus and MRSA nasal carriage among the patients was 42% and 32%,
      respectively. MRSA carriage rate of the patients hospitalised in medical ICUs was
      significantly higher than that of those hospitalised in surgical ICUs (47% vs
      16%, P<0.001). Multivariate logistic regression analysis revealed that pneumonia,
      chronic obstructive pulmonary disease, current MRSA infection, and medical ICU
      admission were independent predictors for nasal carriage of MRSA. Of the 38 MRSA
      isolates available for molecular analysis, a total of six pulsed-field gel
      electrophoresis (PFGE) patterns with two major patterns (F, 42%; A, 37%) were
      identified. Most MRSA isolates belonged to one of two major clones characterised
      as sequence type 5/PFGE F/staphylococcal cassette chromosome mec (SCCmec)
      II/Panton-Valentine leucocidin (PVL) genes negative (34%) and ST239/PFGE A/SCCmec
      III/PVL negative (26%), both clones being associated with healthcare-associated
      (HA) clones in Taiwan. Six isolates (16%) were characterised as ST59/SCCmec IV or
      V(T) and were associated with community strains in Taiwan. In conclusion, 32% of
      ICU hospitalised adult patients in a Taiwanese tertiary care teaching hospital
      between June and July 2008 were colonised with MRSA in their nares. Though most
      isolates were HA-MRSA, community strains accounted for a proportion of the
      isolates.

PMID- 20153555
TI  - [Prognostic factors of mortality in a cohort of patients with in-hospital
      cardiorespiratory arrest].
AB  - OBJECTIVE: To define the prognostic factors related with mortality of patients
      who suffer cardiorespiratory arrest (CRA) in the hospital, according to Utstein
      style guidelines. DESIGN: A descriptive and prospective study covering a 30-month
      consecutive period of all the patients who suffered at least one episode of in
      hospital CRA. A Cox regression multivariate analysis was made to identify the
      independent factors associated with mortality. SETTING: A medical-surgical center
      in Hospital "Virgen de las Nieves" (HUVN), Granada (Spain). PATIENTS: All the
      patients attended due to CRA in the hospital, except for those occurring in the
      operating and recovery room areas. They were followed-up to hospital discharge.
      MAIN VARIABLES: Mortality on hospital discharge. RESULTS: 203 patients who
      suffered at least one cardiorespiratory arrest in the hospital, with a median age
      of 67 years and preponderance of male (60.6%). The most common location was in
      intensive care medicine unit (48%) and cardiac etiology (62%). Hospital survival
      rate was 23.15%. In multivariate analysis, strong predictors of mortality were
      administration of any dose of epinephrine during resuscitation maneuvers (OR 3.4;
      CI 95%. 1.6-7), total duration of resuscitation (HR 1.018; CI 95%, 1.012-1.024)
      and as protective factors the first ventricular fibrillation/ventricular
      tachycardia rhythm with no pulse (HR 0.6; CI 95%, 0.4-0.9) and witnessed by a
      doctor (HR 0.6; CI 95%, 0.5-0.9). CONCLUSIONS: The type of witness was identified
      among the predictors of mortality on hospital discharge after an episode of
      cardiac arrest. This becomes important because the qualification of healthcare
      personnel can be improved through adequate training.

PMID- 20153556
TI  - [Impact of the Tobacco Law on the workplace: a follow up study of a cohort of
      workers in Spain 2005-2007].
AB  - OBJECTIVE: The aim of this study is to describe the changes caused by the Law on
      Tobacco and its consumption in workers who are active smokers. DESIGN: A post
      intervention follow up study of a cohort of users. SETTING: Health Centres in
      Valencia and Majorca. PARTICIPANTS: Users who attended health centres.
      INTERVENTION: The field work consisted of each patient filling in a case report
      form with the requested information. MAIN MEASUREMENTS: The variables collected
      were, sex, place of work, education level, number of workers in the company,
      number of cigarettes smoked. They were told that on the following day they had to
      count the cigarettes smoked throughout the day, noting whether they had been
      smoked during or outside working hours. If they smoked during working hours, they
      reported whether it was inside or outside the workplace. On the following day
      they were telephoned to let us know the number of cigarettes smoked. This
      telephone call was repeated at six months and eighteen months. RESULTS: Smoking
      prevalence and the number of cigarettes smoked in the workplace has been reduced
      by 9% per month. The variables associated with compliance with the law were
      education level, the sex of the worker, and the size of the company. CONCLUSIONS:
      The coming into force of the Tobacco Law has been effective.

PMID- 20153557
TI  - [Peritoneo-scrotal communication: demonstration by 99mTc nanocoloid
      scintigraphy].

PMID- 20153558
TI  - The changing etiology of fever of intermediate duration.
AB  - BACKGROUND: Fever of intermediate duration (FID) is a common condition.
      Currently, its most frequent causes are not well defined. METHODS: Prospective
      study of FID cases attended at a hospital in 2 periods: 1983-1989 and 2004-2005.
      Blood cultures and serologic studies for Brucella melitensis, Coxiella burnetii,
      Rickettsia typhi, Rickettsia conorii, cytomegalovirus, and Epstein-Barr virus
      were performed on all patients. Other microbiological, serological, radiological,
      or invasive procedures were performed according to clinician-in-charge criteria.
      RESULTS: A total of 505 patients were included from 1983 to 1989, and 179 from
      2004 to 2005. A diagnosis was reached in 410 (81.1%) and 109 patients (60.9%),
      respectively. The cause of FID was an infectious disease in 389 patients from the
      first period (94.8% of those with a final diagnosis) and 92 from the second
      (84.4%). Most were systemic infections, 328 (80%) in 1983-1989 and 74 (67.8%) in
      2004-2005, followed by focal infections, 9.5% and 16.5%, respectively. Q fever
      was the most frequent etiology in both periods. In 2004-2005, brucellosis
      decreased and HIV infection emerged as a cause of FID. The origin of FID was non
      infectious in 5.1% and 15.5%, respectively. CONCLUSIONS: Q fever is the most
      frequent cause of FID in southern Spain. Studies over time are needed to identify
      changes in the etiologic spectrum of this condition. Important viral etiologies,
      such as HIV infection, may be detected as causes of FID. Further studies are
      needed to determine the importance of other agents as causes of FID.

PMID- 20153559
TI  - Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of
      chalcones and influence of A-ring modifications on the pharmacological effect.
AB  - Besides 2',4'-dihydroxy-4,6'-dimethoxy-3'-prenylchalcone (1) and 4-acetoxy-2',4'
      dihydroxy-6'-methoxy-3'-prenylchalkon (2), both phase II metabolites of
      xanthohumol in rats, also a principally new chalcone 3'-coumaroyl-2',4,4'
      trihydroxy-6'-methoxychalcone (3), structurally derived from helichrysetin (4) by
      introducing a second coumaroyl substructure at C-3' was synthesized. Furthermore
      new chalcones were synthesized by combination of the B-Ring fragments of
      helichrysetin, xanthohumol, xanthohumol C and xanthohumol H with ferulic or
      caffeic acid moieties in Ring A. Compound 3 showed the highest cytotoxic activity
      against HeLa cells with an IC50 value of 7.3+/-0.4 microM. Anti-oxidative effects
      were determined in the ORAC assay and revealed very strong activity for 3 and 3
      methoxyhelichrysetin (6) exhibiting 7.7+/-0.3 and 6.0+/-1.3 Trolox equivalents,
      respectively. The anti-inflammatory activity of all compounds was measured in an
      in vitro ICAM-1 assay with human microvascular endothelial cells (HMEC-1) and
      compared with the activity of other structurally related chalcones. The results
      showed increasing anti-inflammatory activity for the new synthetic chalcones
      exhibiting a caffeoyl substructure with 3-hydroxyhelichrysetin (5) and 3
      hydroxyxanthohumol H (14) being the most active. At 10 microM the TNFalpha
      induced expression of ICAM-1 was significantly reduced to 65.8 and 69.6% of
      control, respectively.

PMID- 20153560
TI  - Synthesis and preliminary evaluation of peptidomimetic inhibitors of human beta
      secretase.
AB  - Based on the structure of OM99-2 and the X-ray crystal structure of its complex
      with beta-secretase, a series of compounds containing the Leu*Ala hydroxyethylene
      isostere as a scissile bond substitution were designed. 31 compounds were
      synthesized and their beta-secretase inhibition activities were measured. It was
      found that isobutyl group was a better R3 substitution as C-terminus in our
      target compounds, and 4-nitrobenzyl group was the best R2 side chain. With the
      aid of molecular modeling, the binding modes of compounds 9 and 22 with beta
      secretase were compared. The result revealed a stronger bonding mode of 22 than
      9. This explored that the optimal length of this series of peptidomimetic
      inhibitors was P3-P2'. The molecular weights of compounds with this length are
      around 600.

PMID- 20153561
TI  - Theoretical models of pentamidine analogs activity based on their DNA minor
      groove complexes.
AB  - The B-DNA binding property of pentamidine analogs was analyzed employing
      molecular dynamic simulations and UV-vis absorption spectroscopy. Their AATT and
      ATAT sequence preferences were also examined. In theoretical energy computations,
      we considered two solvation models: the implicit model I, where the solvent is
      characterized by a dielectric constant and the explicit model E, where water
      molecules are treated as discrete entities. The binding energy correlates well
      with the increase of melting temperature of the 5'-d(CGCGAATTCGCG)(2)-3' and 5'
      d(CGCGATATCGCG)(2)-3' dodecamers after complexation with ligands (DeltaTm), and
      deduced models predicted adequately the DNA affinities of the studied diamidines.

PMID- 20153562
TI  - Synthesis, characterization and cytotoxicity of iodo-bridged binuclear
      platinum(II) complexes.
AB  - Seven new iodo-bridged binuclear platinum(II) complexes [Pt(L)I2]2 (1-7) (L=n
      butylamine, isopropylamine, m-toluidine, p-toluidine, diethylamine, N
      methylaniline and aniline) have been synthesized and characterized by elemental
      analysis, conductivity, thermal analysis, IR, 1H NMR and mass spectra techniques.
      The cytotoxicity was tested by MTT assay. The results indicate that they have
      selectivity against tested carcinoma cell lines. For example, the complexes (3
      and 7) have better cytotoxicity than cisplatin against Bel-7402 cell line, the
      complexes (2-5 and 7) have better cytotoxicity than cisplatin against Hela cell
      line. The results suggest that the species of amine has important effect on
      cytotoxicity, when L=m-toluidine, p-toluidine and aniline, the complexes have
      better cytotoxicity against tested carcinoma cell lines.

PMID- 20153563
TI  - Hybrids of 3alpha-methoxyserrat-14-en-21beta-ol (PJ-1) and 3beta-methoxyserrat-14
      en-21beta-ol (PJ-2) and various anti-oxidants as cancer chemopreventive agents.
AB  - 3alpha-methoxyserrat-14-en-21beta-ol (1) and 3beta-methoxyserrat-14-en-21beta-ol
      (2) and their conjugates with curcumin, kojic acid, quercetin, and baicalein (3
      18), as well as new analogs (19-24) derived from 1 and 2, were tested for their
      inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation
      induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of
      16 (IC50=330 mol ratio/32 pmol/TPA), 9 (IC50=335), 10 (IC50=338), and 15
      (IC50=350) were stronger than those of the other compounds and the positive
      control, oleanolic acid (IC50=449). Compounds 15 and 16, which are conjugates of
      one molecule each of 1 or 2 and quercetin, inhibited mouse skin tumor promotion
      in an in vivo two-stage carcinogenesis model. The in vivo two-stage mouse skin
      carcinogenesis test employed 7,12-dimethylbenz[a]anthracene (DMBA) as an
      initiator and TPA as a promoter.

PMID- 20153564
TI  - Catalytic nanomedicine: a new field in antitumor treatment using supported
      platinum nanoparticles. In vitro DNA degradation and in vivo tests with C6 animal
      model on Wistar rats.
AB  - Novel nanostructured TiO2 and SiO2 based biocatalysts, with 3-4 wt. % of Pt have
      been developed. The obtained materials exhibit a high surface area together with
      a broad pore size distribution. The method of synthesis allowed obtaining high
      dispersed platinum metal nanoparticles. In vitro DNA reactivity test of the
      biocatalysts were carried out by electrophoresis and formation of DNA adducts was
      observed. The most active biocatalyst was H2PtCl6/SiO2. These biocatalysts were
      also tested in an experimental model of C6 brain tumours in Wistar rats.
      Administration of the material was made by stereotactic brain surgery to place it
      directly in the malignant tissue. A significant decrease in tumour size and
      weight as well as morphologic changes in cancer cells were observed.

PMID- 20153565
TI  - Computational screening for membrane-directed inhibitors of mast cell activation.
AB  - Receptor-mediated signaling events frequently depend on the integrity of their
      membrane environments. Only a limited number of compounds are currently available
      that are known or thought to modulate membrane environments and affect signaling
      events without disrupting membrane structure. Among these are alkylphospholipids
      including the drug miltefosine that is approved for the treatment of breast
      cancer and leishmaniasis. In addition, miltefosine has recently been shown to
      block immunoglobulin E receptor-dependent mast cell activation. On the basis of
      these findings, we have explored other alkylphospholipids as potential inhibitors
      of mast cell activation and confirmed the inhibitory activity of five molecules.
      By comparing the head groups of these alkylphospolipids common pharmacophore
      features were determined. Through computational screening utilizing this
      pharmacophore information a new lipid-like inhibitory chemotype was identified
      that blocked mast cell activation with potency comparable to miltefosine.

PMID- 20153566
TI  - Investigation on the isoform selectivity of histone deacetylase inhibitors using
      chemical feature based pharmacophore and docking approaches.
AB  - A three dimensional (3D) chemical feature based pharmacophore model was developed
      for selective histone deacetylase 1 (HDAC1) inhibitors, which provides an
      efficient way to discuss the isoform selectivity of HDAC inhibitors. In contrast
      to the classical pan-HDAC pharmacophore, two hydrophobic features (HY and HYAr2)
      were found in the chemical feature based pharmacophore model, which might be
      responsible for the selectivity of HDAC1 inhibitions. Molecular docking also
      highlighted the two hydrophobic features, which are located in the internal
      cavity adjacent to the active site. The results contribute to our understanding
      of the molecular mechanism underlying the selectivity of HDAC1 inhibitors and
      suggest a possible target region to design novel selective HDAC1 inhibitors.

PMID- 20153567
TI  - Prediction of air to liver partition coefficient for volatile organic compounds
      using QSAR approaches.
AB  - In this work a quantitative structure-activity relationship (QSAR) technique was
      developed to investigate the air to liver partition coefficient (log Kliver) for
      volatile organic compounds (VOCs). Suitable set of molecular descriptors was
      calculated and the important descriptors were selected by GA-PLS methods. These
      variables were served as inputs to generate neural networks. After optimization
      and training of the networks, they were used for the calculation of log Kliver
      for the validation set. The root mean square errors for the neural network
      calculated log Kliver of training, test, and validation sets are 0.100, 0.091,
      and 0.112, respectively. Results obtained reveal the reliability and good
      predictivity of neural network for the prediction of air to liver partition
      coefficient for volatile organic compounds.

PMID- 20153568
TI  - Photodynamic inactivation of Escherichia coli and Streptococcus mitis by cationic
      zinc(II) phthalocyanines in media with blood derivatives.
AB  - The photodynamic inactivation (PDI) of Escherichia coli and Streptococcus mitis
      sensitized by cationic phthalocyanines was studied in different media containing
      blood derivatives. First, the activity of zinc(II) tetramethyltetrapyridino[3,4
      b:3',4'-g:3'',4''-l:3''',4'''-q]porphyrazinium (ZnAPc4+), zinc(II) 2,9,16,23
      tetrakis[4-(N-methylpyridyloxy)]phthalocyanine (ZnPPc4+) and zinc(II) 2,9,16,23
      tetrakis[2-(N,N,N-trimethylamino)ethoxy]phthalocyanine (ZnEPc4+) were compared to
      photoinactivate these bacteria in saline solutions. After visible light
      irradiation, a higher photoinactivation of E. coli cells was found for ZnPPc4+,
      while ZnEPc4+ was the more effective sensitizer to eradicate S. mitis cells. In
      the presence of human red blood (HRB) cells, two aspects were analyzed: the
      photohemolysis induced by these cationic phthalocyanines and the PDI of bacteria
      in medium containing erythrocytes. The highest photohemolytic damage was produced
      by ZnPPc4+, which can be avoided using azida ion as photoprotective quencher. In
      both bacteria, the photoinactivation is possible in presence of HRB cells.
      Mainly, ZnEPc4+ is effective to photoinactivate S. mitis with a low hemolysis of
      erythrocytes. However, inactivation of E. coli by ZnPPc4+ decreases in medium
      with HRB cells, further when azide ion is added to avoid hemolysis. The presence
      of plasma considerable reduces the photocytotoxic effect, which mainly affects
      the eradication of E. coli. However, the PDI of S. mitis by ZnEPc4+ is even
      possible in presence of blood derivatives.

PMID- 20153569
TI  - Synthesis and characterization of neurostatin-related compounds with high
      inhibitory activity of glioma growth.
AB  - O-acetyl-ganglioside neurostatin, (Galbeta1-->3GalNAcbeta1-->4[9-O-Ac
      Neu5Acalpha2-->8Neu5Acalpha2-->3]Galbeta1-->4Glcbeta1-->1'-ceramide), is a
      natural GD1b-derived inhibitor of astroblast and astrocytoma division, whose
      structure and purification method limits its availability and stability.
      Therefore, we set-up the reaction to obtain O-acetylated and O-butyrylated
      neurostatin analogs by chemical synthesis, in order to improve its availability
      and stability. The compounds antitumoral activity was evaluated on U373MG and C6
      glioblastoma cells, observing that the O-acetylation-dependent increase in the
      inhibitory activity was enhanced by O-butyrylation, with no further improvement
      with the multi-substitution, pointing to the initial conformational change and
      the stability change as responsible of its function. These results open the
      possibility for the application of the neurostatin-related compounds to in-vivo
      tumoral models.

PMID- 20153570
TI  - Relation of ghrelin, leptin and inflammatory markers to nutritional status in
      active pulmonary tuberculosis.
AB  - BACKGROUNDS & AIMS: Malnutrition is a prominent feature of tuberculosis. Little
      is known about the role of the appetite-related hormones, ghrelin and leptin, in
      malnutrition in tuberculosis. This study was undertaken to determine whether
      ghrelin and leptin contribute to malnutrition in active pulmonary tuberculosis.
      METHODS: Nutritional parameters and plasma levels of ghrelin, leptin, and
      inflammatory cytokines were measured before treatment and after clinical
      improvement following anti-tuberculosis chemotherapy in 23 tuberculosis subjects
      and 23 healthy controls prospectively. Patients were divided into well-nourished
      (n=15) and malnourished (n=8) groups. RESULTS: Ghrelin but not leptin levels were
      significantly lower in the malnourished tuberculosis group than in the well
      nourished tuberculosis group [44.0 (43.0-54.0) vs. 122 (108-158)pg/mL; p<0.05].
      Malnutrition score was negatively correlated to ghrelin (rho=-0.76, p<0.01) but
      not to leptin levels. TNF-alpha and IL-6 levels were significantly higher in the
      malnourished tuberculosis group than in the well-nourished tuberculosis group and
      controls. Plasma levels of ghrelin tended to decrease as inflammatory cytokines
      increased before treatment. CONCLUSIONS: Decreased plasma ghrelin levels, in
      addition to increased plasma inflammatory cytokine levels, may be associated with
      malnutrition in active pulmonary tuberculosis.

PMID- 20153571
TI  - Short communication articles published in BJOMS during 2008-2009--an analysis of
      types of submission and subject material.
AB  - The British Journal of Oral and Maxillofacial Surgery (BJOMS) accepts many types
      of papers that include leading articles, reviews, full length articles, and short
      communications. Many of the latter are isolated case reports of rare or
      interesting pathology, or personal experience of a difficult or unexpected
      complication. Case reports are considered to have a relatively low value in the
      advancement of medical knowledge, and with increasing pressure for space in paper
      publications, many journals now limit them to online publication only. We
      evaluated all 142 short communications published in BJOMS during 2008/2009. Most
      (87%) were single case reports, and they covered virtually the whole remit of the
      specialty. There were also 14 formal studies that included two laboratory-based
      research projects; these were excluded from the analysis. We used established
      criteria to assess the possible educational value of each publication, and found
      that 61/128 papers (48%), while interesting and informative, probably added
      little to existing knowledge. The remaining papers described new or unreported
      cases, rare or unexpected outcomes, and adverse effects or complications of
      treatment. We discuss the possible implications of this study for readers of
      BJOMS and for the journal itself.

PMID- 20153573
TI  - Defining near misses: towards a sharpened definition based on empirical data
      about error handling processes.
AB  - Medical errors in health care still occur frequently. Unfortunately, errors
      cannot be completely prevented and 100% safety can never be achieved. Therefore,
      in addition to error reduction strategies, health care organisations could also
      implement strategies that promote timely error detection and correction.
      Reporting and analysis of so-called near misses - usually defined as incidents
      without adverse consequences for patients - are necessary to gather information
      about successful error recovery mechanisms. This study establishes the need for a
      clearer and more consistent definition of near misses to enable large-scale
      reporting and analysis in order to obtain such information. Qualitative incident
      reports and interviews were collected on four units of two Dutch general
      hospitals. Analysis of the 143 accompanying error handling processes demonstrated
      that different incident types each provide unique information about error
      handling. Specifically, error handling processes underlying incidents that did
      not reach the patient differed significantly from those of incidents that reached
      the patient, irrespective of harm, because of successful countermeasures that had
      been taken after error detection. We put forward two possible definitions of near
      misses and argue that, from a practical point of view, the optimal definition may
      be contingent on organisational context. Both proposed definitions could yield
      large-scale reporting of near misses. Subsequent analysis could enable health
      care organisations to improve the safety and quality of care proactively by (1)
      eliminating failure factors before real accidents occur, (2) enhancing their
      ability to intercept errors in time, and (3) improving their safety culture.

PMID- 20153574
TI  - Anaphylaxis to mefenamic acid in a patient with new onset of systemic lupus
      erythematosus.

PMID- 20153575
TI  - The prevalence of aspirin-induced asthma in Saudian asthmatic patients.
AB  - BACKGROUND: Aspirin-induced asthma (AIA), is a distinct clinical syndrome
      affecting some asthmatic patients. Although the name of the condition relates to
      aspirin, it is well established that affected patients are cross-sensitive to all
      non-steroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: Assessing the
      prevalence of AIA among Saudian asthmatic patients. METHODS: This is a
      retrospective study of the medical records of asthmatic patients. RESULTS: The
      prevalence of AIA in the patients studied was found to be 12.6%. Statistical
      analyses indicated that AIA was associated with more severe asthma [odds ratio
      (OR) (95% Confidence interval (CI)) in Group I cases 2.86 (1.24 to 6.59)
      respectively (p<0.05)]. The results showed that some allergic conditions were
      significantly more common in Group I for allergic rhinitis (OR=2.19, 95% CI 0.89
      5.37, p<0.05), pollinosis (OR=1.59, 95% CI 0.85-2.98, p<0.05) for antibiotic
      allergy (OR=1.25, 95% CI 0.65-2.41, p<0.05) and for atopic dermatitis (OR=1.34,
      95% CI 0.70-2.55, p<0.05). Family history of allergy had a more significant role
      in Group I cases (OR=1.27, 95% CI 0.68-2.37, p<0.05). No gender difference on
      asthma severity was detected in either group (Chi(2)=2.19, p>0.05). CONCLUSION:
      The prevalence of respiratory symptoms triggered by aspirin/NSAID use was 12.6%
      in the asthmatics studied. AIA appears to be a significant problem and further
      investigations of the mechanisms of these responses and the possible link between
      this syndrome and other allergic co-morbidities are required.

PMID- 20153576
TI  - Inhibition of the transcriptional function of p53 by EWS-Fli1 chimeric protein in
      Ewing Family Tumors.
AB  - The chromosomal translocation t(11;22)(q24;q12) generates the EWS-Fli1 fusion
      gene, which contributes to the development of Ewing Family Tumors (EFTs).
      Although p53 mutations are found only in 5-20% of EFTs, the p53 pathway is
      thought to be abrogated in EFTs. The role of EWS-Fli1 in the p53 pathway in the
      tumor is still poorly understood. In this study, using immunoprecipitation and co
      localization, we show that EWS-Fli1 interacts with p53 within the nucleus in
      vivo. The introduction of EWS-Fli1 resulted in significant reduction of promoter
      activities and mRNA levels of p21 and mdm2, meanwhile it canceled p53-dependent
      growth suppression. In contrast, knockdown of EWS-Fli1 expression mediated by
      small interfering RNAs (siRNA) also augmented the induction of p21 and mdm2 in
      response to DNA damage. Furthermore, using serial deletion constructs of the EWS
      Fli1 fusion protein, we determined that EWS-Fli1 binding to p53 as well as
      inhibition of p21 and mdm2 promoter activities was mediated by its N-terminal
      domain (amino acid residues 65-109). These observations suggest that the N
      terminal region of EWS-Fli1 might associate with p53 and impair its
      transcriptional activity, subsequently inhibiting the expression of its
      downstream genes. These results might provide new insight into the oncogenesis of
      EFTs by EWS-Fli1 via the inhibition of p53 function.

PMID- 20153577
TI  - Field rates for natural attenuation of arsenic in Tinto Santa Rosa acid mine
      drainage (SW Spain).
AB  - Reactive transport modelling of the main processes related to the arsenic natural
      attenuation observed in the acid mine drainage (AMD) impacted stream of Tinto
      Santa Rosa (SW Spain) was performed. Despite the simplicity of the kinetic
      expressions used to deal with arsenic attenuation processes, the model reproduced
      successfully the major chemical trends observed along the acid discharge. Results
      indicated that the rate of ferrous iron oxidation was similar to the one obtained
      in earlier field studies in which microbial catalysis is reported to occur. With
      regard to the scaled arsenic oxidation rate, it is one order of magnitude faster
      than the values obtained under laboratory conditions suggesting the existence of
      a catalytic agent in the natural system. Schwertmannite precipitation rate, which
      was represented by a simple kinetic expression relying on Fe(III) and pH, was in
      the range calculated for other AMD impacted sites. Finally, the obtained
      distribution coefficients used for representing arsenic sorption onto Fe(III)
      precipitates were lower than those deduced from reported laboratory data. This
      discrepancy is attributed to a decrease in the schwertmannite arsenate sorption
      capacity as sulphate increases in the solution.

PMID- 20153578
TI  - Influence of velocity gradient in a hydraulic flocculator on NOM removal by
      aerated spiral-wound ultrafiltration membranes (ASWUF).
AB  - A hydraulic coagulation-flocculation processes combined with aerated spiral-wound
      ultrafiltration membranes (ASWUF) was designed with the objective of improving
      natural organic matter (NOM) removal by ASWUF in the treatment of water for human
      consumption. The pilot-scale experimental system had capacity for treating 0.9
      m(3)/h. Dosage of Cl(3)Fe as coagulant and hydraulic retention time (HRT) were
      calculated to generate microflocculation and different velocity gradients (G=27,
      47, 87 and 104 s(-1)) were applied in the hydraulic flocculator. Operating alone,
      the ASWUF system achieved an NOM removal performance of 39% without problems of
      membrane clogging, although there was a significant correlation between effluent
      and influent quality. Application of microflocculation achieved considerable
      improvement in NOM removal, but values of G< or =87 s(-1) resulted in rapid
      clogging of the membrane due to flocs disintegration in the aerated membrane
      tank. Particle analysis revealed that the reduction of the velocity gradient had
      the effect of inclining the particle size distribution towards larger sizes,
      affecting both NOM removal capacity and membrane clogging. For G=104 s(-1) an NOM
      removal yield of 90% was reached, while transmembrane pressure (TMP) was
      stabilised as a result of the control of membrane clogging.

PMID- 20153579
TI  - Heavy metal concentrations and toxicity in water and sediment from stormwater
      ponds and sedimentation tanks.
AB  - Sedimentation is a widely used technique in structural best management practices
      to remove pollutants from stormwater. However, concerns have been expressed about
      the environmental impacts that may be exerted by the trapped pollutants. This
      study has concentrated on stormwater ponds and sedimentation tanks and reports on
      the accumulated metal concentrations (Cd, Cr, Ni, Pb, and Zn) and the associated
      toxicity to the bacteria Vibrio fischeri. The metal concentrations are compared
      with guidelines and the toxicity results are assessed in relation to samples for
      which metal concentrations either exceed or conform to these values. The water
      phase metal concentrations were highest in the ponds whereas the sedimentation
      tanks exhibited a distinct decrease towards the outlet. However, none of the
      water samples demonstrated toxicity even though the concentrations of Cu, Pb, and
      Zn exceeded the threshold values for the compared guidelines. The facilities with
      higher traffic intensities had elevated sediment concentrations of Cr, Cu, Ni,
      and Zn which increased towards the outlet for the sedimentation tanks in
      agreement with the highest percentage of fine particles. The sediments in both
      treatment facilities exhibited the expected toxic responses in line with their
      affinity for heavy metals but the role of organic carbon content is highlighted.

PMID- 20153580
TI  - Advanced purification of petroleum refinery wastewater by catalytic vacuum
      distillation.
AB  - In our work, a new process, catalytic vacuum distillation (CVD) was utilized for
      purification of petroleum refinery wastewater that was characteristic of high
      chemical oxygen demand (COD) and salinity. Moreover, various common promoters,
      like FeCl(3), kaolin, H(2)SO(4) and NaOH were investigated to improve the
      purification efficiency of CVD. Here, the purification efficiency was estimated
      by COD testing, electrolytic conductivity, UV-vis spectrum, gas chromatography
      mass spectrometry (GC-MS) and pH value. The results showed that NaOH promoted CVD
      displayed higher efficiency in purification of refinery wastewater than other
      systems, where the pellucid effluents with low salinity and high COD removal
      efficiency (99%) were obtained after treatment, and the corresponding pH values
      of effluents varied from 7 to 9. Furthermore, environment estimation was also
      tested and the results showed that the effluent had no influence on plant growth.
      Thus, based on satisfied removal efficiency of COD and salinity achieved
      simultaneously, NaOH promoted CVD process is an effective approach to purify
      petroleum refinery wastewater.

PMID- 20153581
TI  - Pain - not just a feeling, but a working brain.

PMID- 20153582
TI  - Cause or effect? Deconditioning and chronic low back pain.

PMID- 20153584
TI  - Acute and chronic stress increase DHEAS concentrations in rhesus monkeys.
AB  - Most studies on the stress-responsiveness of the hypothalamic-pituitary-adrenal
      (HPA) axis have focused on glucocorticoids, while few studies have investigated
      the adrenal secretion of dehydroepiandrosterone sulfate (DHEAS), which is unique
      to primates. Monkeys were chair-restrained for 2h per day for seven consecutive
      days, and blood samples were collected upon placement in the chair, and at 15,
      30, 60 and 120 min later. Like cortisol, DHEAS concentrations increased
      throughout the initial session of chair restraint (acute stress). Unlike the
      cortisol response, which decreased after repeated exposure to the stressor, the
      DHEAS response was sustained throughout the seventh session of restraint (chronic
      stress) and response to the seventh session of restraint did not differ from the
      DHEAS response to the initial session. Like cortisol, DHEAS concentrations showed
      a diurnal rhythm with higher concentrations in the morning compared to the
      evening and a decrease in response to dexamethasone (DEX) administration. After
      repeated exposure to the stressor, the suppression of DHEAS in response to
      dexamethasone was more complete, suggesting an increase in negative feedback
      sensitivity. These data show that DHEAS concentrations increase in response to
      both acute and chronic (repeated) stress and provide another measure of HPA
      activity that parallels cortisol during acute responses to stress but diverges in
      chronic or repeated stress.

PMID- 20153585
TI  - Natural variations in maternal and paternal care are associated with systematic
      changes in oxytocin following parent-infant contact.
AB  - Animal studies have demonstrated that the neuropeptide oxytocin (OT) plays a
      critical role in processes of parent-infant bonding through mechanisms of early
      parental care, particularly maternal grooming and contact. Yet, the involvement
      of OT in human parenting remains poorly understood, no data are available on the
      role of OT in the development of human fathering, and the links between patterns
      of parental care and the OT response have not been explored in humans. One
      hundred and twelve mothers and fathers engaged in a 15-min play-and-contact
      interaction with their 4-6-month-old infants and interactions were micro-coded
      for patterns of parental touch. Results showed that baseline levels of plasma and
      salivary OT in mothers and fathers were similar, OT levels in plasma and saliva
      were inter-related, and OT was associated with the parent-specific mode of
      tactile contact. Human mothers who provided high levels of affectionate contact
      showed an OT increase following mother-infant interaction but such increase was
      not observed among mothers displaying low levels of affectionate contact. Among
      fathers, only those exhibiting high levels of stimulatory contact showed an OT
      increase. These results demonstrate consistency in the neuroendocrine basis of
      human parental interactions with those seen in other mammals. The findings
      underscore the need to provide opportunities for paternal care to trigger the
      biological basis of fatherhood and suggest that interventions that permit social
      engagement may be recommended in conditions of diminished maternal-infant
      contact, such as prematurity or postpartum depression.

PMID- 20153586
TI  - Alcoholism, associated risk factors, and harsh parenting among fathers: Examining
      the role of marital aggression.
AB  - This study utilized a longitudinal design to examine relations between paternal
      alcoholism, paternal psychopathology, marital aggression and fathers' harsh
      parenting behavior in a sample of children with alcoholic (n = 89) and non
      alcoholic (n = 94) fathers. Structural Equation Modeling revealed that paternal
      alcoholism, depression, and antisocial behavior at 12 months of child age each
      predicted higher levels of marital aggression at 36 months. Moreover, after
      controlling for prior parenting, marital aggression was predictive of harsher
      parenting at kindergarten. Alcoholism and psychopathology were not directly
      predictive of harsh parenting with marital aggression included in the model, thus
      indicating that marital aggression is mediating the relation between paternal
      risk factors and parenting outcome. Results of this study suggest that one
      pathway linking fathers' alcohol diagnosis to harsh parenting is via marital
      aggression.

PMID- 20153587
TI  - Perceptions of alcohol policy and drinking behavior: Results of a latent class
      analysis of college student drinkers.
AB  - OBJECTIVE: The purpose of this study was to extend the limited research on
      college student support for alcohol control policies by using a latent class
      analysis to examine the shared characteristics of drinking students who support
      or oppose such policies. METHODS: We used data from a sample of 2393 students
      drawn from a larger study on high risk drinking at a mid-western university. Data
      was collected between October 2005 and May 2007. We conducted a latent class
      analysis to identify sub-groups of drinking students based on relevant variables.
      RESULTS: The results of the latent class analysis yielded a model which could
      correctly classify 90% of the students taking the survey into one of four
      "classes" based upon their response to four items on the questionnaire.
      CONCLUSIONS: Interventions would benefit from approaches that target both student
      perceptions and specific policies that are most conducive to student support and
      engagement.

PMID- 20153588
TI  - Model of pulmonary fluid traffic homeostasis based on respiratory cycle pressure,
      bidirectional bronchiolo-pulmonar shunting and water evaporation.
AB  - The main puzzle of the pulmonary circulation is how the alveolar spaces remain
      dry over a wide range of pulmonary vascular pressures and blood flows. Although
      normal hydrostatic pressure in pulmonary capillaries is probably always below 10
      mmHg, well bellow plasma colloid pressure of 25 mmHg, most textbooks state that
      some fluid filtration through capillary walls does occur, while the increased
      lymph drainage prevents alveolar fluid accumulation. The lack of a measurable
      pressure drop along pulmonary capillaries makes the classic description of
      Starling forces unsuitable to the low pressure, low resistance pulmonary
      circulation. Here presented model of pulmonary fluid traffic describes lungs as a
      matrix of small vascular units, each consisting of alveoli whose capillaries are
      anastomotically linked to the bronchiolar capillaries perfused by a single
      bronchiolar arteriole. It proposes that filtration and absorption in pulmonary
      and in bronchiolar capillaries happen as alternating periods of low and of
      increased perfusion pressures. The model is based on three levels of filtration
      control: short filtration phases due to respiratory cycle of the whole lung are
      modulated by bidirectional bronchiolo-pulmonar shunting independently in each
      small vascular unit, while fluid evaporation from alveolar groups further tunes
      local filtration. These mechanisms are used to describe a self-sustaining
      regulator that allows optimal fluid traffic in different settings. The proposed
      concept is used to describe development of pulmonary edema in several clinical
      entities (exercise in wet or dry climate, left heart failure, people who rapidly
      move to high altitudes, acute cyanide and carbon monoxide poisoning, large
      pulmonary embolisms).

PMID- 20153589
TI  - Differences in two-component signal transduction proteins among the genus
      Brucella: implications for host preference and pathogenesis.
AB  - Two-component systems (TCSs) are the predominant bacterial signal transduction
      mechanisms. Species of the genus Brucella are genetically highly related and
      differ mainly in mammalian host adaptation and pathogenesis. In this study, TCS
      proteins encoded in the available genome sequences of Brucella species have been
      identified using bioinformatic methods. All the Brucella species share an
      identical set of TCS proteins, and the number of TCS proteins in the closely
      related opportunistic human pathogen Ochrobactrum anthropi was higher than in
      Brucella species as expected from its lifestyle. O. anthropi lacks orthologs of
      the Brucella TCSs NodVW, TceSR and TcfSR, suggesting that these TCS proteins
      could be necessary for the adaptation of Brucella as an intracellular pathogen.
      This genomic analysis revealed the presence of a differential distribution of TCS
      pseudogenes among Brucella species. Moreover, there were also differences in TCS
      pseudogenes between strains belonging to the same Brucella species, and in
      particular between B. suis biovars 1 and 2.

PMID- 20153590
TI  - The functional effects of nutrients on enterocyte proliferation and intestinal
      ion transport in early infancy.
AB  - Nutrition has a key role in the modulation of the developing intestine in early
      infancy, and nutrients are able to modulate several intestinal functions
      including nutrient absorption, ion transport, cell growth and differentiation,
      motility and immunomodulation. Such modulation is exerted in part through a
      direct interaction between a single nutrient and the enterocyte. Two functions-
      ion transport and cell growth--are closely connected and appear to be modulated
      by nutrients. This is supported by the finding that a single nutrient (e.g. zinc)
      stimulates ion absorption and also promotes enterocyte growth. Interestingly,
      intracellular signalling for either effect is similar and involves mitogen
      activated protein kinase. Other nutrients also modulate enterocyte function and
      there is evidence that their effect may depend on their side of action (apical or
      basolateral) and concentration. Knowledge of the interaction between nutrients
      and enterocytes may be exploited to obtain clinical effects using nutrition as a
      long-term treatment for intestinal and non-intestinal conditions.

PMID- 20153591
TI  - Save antibiotics. What can be done to prevent a forecasted disaster! Suggestions
      to promote the development of new antibiotics.
AB  - New antibiotics are needed because of the increasing resistance of bacteria but
      they will be available in years to come only if drastic changes are implemented
      in development strategies, evaluation, use, and financing. Over the last decade,
      various opinions were stated and limited action was undertaken. Optimizing
      antibiotic use (as the "antibiotic plan" in France) was indispensable, but the
      process is still on going, and this is only part of the problem. Major questions
      are recurrently raised such as improvement of development procedures for new
      antibiotics, optimizing diagnostic methods, innovating financing modalities, or
      rescue of "old" antibiotics at risk of being withdrawn from the market. The
      symposium organized in September 2009 by the Swedish EU presidency helped to
      support previous recommendations. But conclusions remain unspecific. The
      propositions which are made here, after a work session, have for aim to be more
      detailed and innovating, even if they can be discussed, or even provocative.

PMID- 20153592
TI  - Phylogenetic diversity and antimicrobial activities of bryozoan-associated
      bacteria isolated from Mediterranean and Baltic Sea habitats.
AB  - To date, only a small number of investigations covering microbe-bryozoa
      associations have been carried out. Most of them have focused on a few bryozoan
      species and none have covered the antibacterial activities of associated
      bacteria. In the current study, the proportion and phylogenetic classification of
      Bryozoan-associated bacteria with antimicrobial properties were investigated.
      Twenty-one specimens of 14 different bryozoan species were collected from several
      sites in the Baltic and the Mediterranean Sea. A total of 340 associated bacteria
      were isolated, and 101 displayed antibiotic activities. While antibiosis was
      predominantly directed against Gram-positive test strains, 16S rRNA gene
      sequencing revealed affiliation of the isolates to Gram-negative classes
      (Flavobacteria, Alpha- and Gammaproteobacteria). One isolate was related to the
      Gram-positive Actinobacteria. The sequences were grouped into 27 phylotypes on
      the basis of similarity values >or=99.5%. A host-specific affiliation was not
      revealed as members of the same phylotype were derived from different bryozoan
      species. Site-specific patterns, however, were demonstrated. Strains of the
      genera Sphingomonas and Alteromonas were exclusively isolated from Mediterranean
      sites, whereas Shewanella, Marinomonas and Vibrio-related isolates were only from
      Baltic sites. Although Pseudoalteromonas affiliated strains were found in both
      habitats, they were separated into respective phylotypes. Isolates with 16S rDNA
      similarity values <98%, which could possibly represent new species, belonged to
      the genera Shewanella, Pseudoalteromonas and Tenacibaculum.

PMID- 20153593
TI  - Evaluation of the use of multilocus sequence analysis (MLSA) to resolve taxonomic
      conflicts within the genus Marichromatium.
AB  - Four species of marine purple sulfur bacteria of the genus Marichromatium have
      been validly described. A recent re-analysis of the 16S rRNA-based similarity and
      genomic DNA-DNA hybridizations (DDH) of the type strains [33] suggested that some
      of them are so closely related that they can be considered heterotypic synonyms.
      Here, we report on the evaluation of the multilocus sequence analysis approach
      (MLSA) for nine Marichromatium strains in order to resolve their intrageneric
      genealogical relationships. MLSA was based on six protein-coding genes (gyrB,
      recA, fusA, dnaK, pufM, and soxB), and the results were comparable to DDH. The
      phylogenetic tree constructed with the concatenated sequences, which also
      included the 16S rRNA gene and the internal transcriber spacer ITS region
      (4331bp), separated the nine strains in four lineages that reflected the four
      Marichromatium species. The reconstructed phylogenetic tree based on
      concatenation of six protein-coding genes was also highly congruent with the tree
      topology based on the 16S rRNA gene.

PMID- 20153594
TI  - Identification, isolation and characterization of new impurity in rabeprazole
      sodium.
AB  - Rabeprazole sodium [1] is a proton pump inhibitor, used as an antiulcerative.
      During the manufacturing of rabeprazole sodium, we observed an unknown impurity
      at levels 0.05-0.1% in HPLC analysis along with the known potential impurities.
      This new unknown impurity was isolated using preparative liquid chromatography.
      Based on the complete spectral analysis ((1)H NMR, (13)C NMR, DEPT, Mass and IR),
      this new impurity was designated as 2-[[(3-methyl-4-(methylthio)-2
      pyridinyl)methyl]sulfinyl]-1H-benzimidazole (methylthio impurity of rabeprazole).
      Impurity isolation, structure elucidation and probable formation mechanism was
      discussed.

PMID- 20153595
TI  - Selectively preparative purification of aristolochic acids and aristololactams
      from Aristolochia plants.
AB  - A novel method has been developed for the purification of aristolochic acids and
      aristololactams compounds from Aristolochia plants, a kind of typically toxic
      traditional Chinese medicine. In this method, Oligo (ethylene glycol) separation
      column which has "clustering function" for compounds in TCMs was used to produce
      the fractions containing the compounds with similar structures. A four-channel
      parallel preparative HPLC with C18 separation column was employed to purify the
      target compounds. The extraction sample of the blending of Radix Aristolochiae,
      Fructus Aristolochiae and Caulis Aristolochiae Manshuriensis was used to develop
      the method. Then, four aristolochic acids and three aristololactams were obtained
      using this method and the chemical identification was confirmed by Q-TOF-MS, (1)H
      NMR and (13)C NMR. Thus, this method can deal with more than one traditional
      Chinese medicine simultaneously. Additionally, the results demonstrated that this
      method was an effective way to purify target compounds selectively from TCMs.

PMID- 20153596
TI  - An LC-MS/MS method for the simultaneous determination of chlorogenic acid,
      forsythiaside A and baicalin in rat plasma and its application to pharmacokinetic
      study of shuang-huang-lian in rats.
AB  - An LC-MS/MS method was developed for the simultaneous determination of
      chlorogenic acid, forsythiaside A and baicalin, three major ingredients in Shuang
      huang-lian preparations, in rat plasma. Following extraction by methanol-ethyl
      acetate-trifluoroacetic acid (49:49:2, v/v/v), the extracted analytes were
      separated on a reverse phase C12 column using a gradient mobile phase system of
      acetonitrile-water containing 0.1% formic acid. The limits of quantification were
      between 1.0 and 2.1ng/mL, the precision was <7% and the accuracy was between 94%
      and 107%. The validated method was applied to a comparative pharmacokinetic study
      in rats after administration of Shuang-huang-lian solutions via intravenous,
      peroral or intratracheal routes. The results showed that the three chemical
      markers were more rapidly and thoroughly absorbed following pulmonary delivery as
      compared with peroral administration.

PMID- 20153597
TI  - A randomized trial of pictorial versus prose-based medication information
      pamphlets.
AB  - OBJECTIVE: The goal of this study was to compare prose and pictorial-based
      information pamphlets about the medication methotrexate in the domains of free
      recall, cued recall, comprehension and utility. METHODS: A single blind,
      randomized trial of picture versus prose-based information pamphlets including
      100 participants aged 18-65 years of age, who had not completed high school,
      could read English, and had no prior knowledge about methotrexate. Superiority of
      pamphlet type was assessed using immediate free recall, cued recall and
      comprehension. RESULTS: There were no differences between picture and prose
      pamphlets in free recall, cued recall, and comprehension either immediately or
      after a 1-week interval. Immediate free recall of important information was 17
      26%; free recall fell even lower to 7-16% after 1 week. The pictorial pamphlet
      was preferred over the prose-based pamphlet. CONCLUSION: This study found no
      benefit in free recall, cued recall, or comprehension through the addition of
      pictograms to a simple prose-based medication pamphlet. PRACTICE IMPLICATIONS: In
      order for them to be effective in clinical practice, even simple medication
      information pamphlets that have been assessed for patients' ability to comprehend
      them cannot be used as the sole means for conveying important medication-related
      information to patients.

PMID- 20153598
TI  - [H1N1 Pandemic flu vaccination: an update on December 18th 2009].

PMID- 20153599
TI  - [Hospitalized patients with 2009 H1N1 influenza in intensive care unit over the
      world, epidemiological assessment in January 2010].

PMID- 20153600
TI  - Acute respiratory distress syndrome following 2009 H1N1 virus pandemic: when ECMO
      come to the patient bedside.

PMID- 20153601
TI  - [Ruptured subcapsular haematoma of the liver. An observed case in an isolated
      maternity of Gabon].

PMID- 20153602
TI  - [What future for a vaccine against tobacco?].

PMID- 20153603
TI  - Development and validation of a questionnaire to measure the service needs of
      families with children with developmental disabilities.
AB  - The aim of this project was to develop and validate a Service Needs Questionnaire
      (SNQ) on the service needs of families with children with developmental
      disabilities. The SNQ and a measure of parenting stress were administered to 105
      parents of children diagnosed with learning/behaviour problems and 233 parents of
      children attending primary schools. Initial Rasch analysis results indicated
      inadequate distinction of the categories and the fit statistics of three items
      were outside the acceptable range. The categories were collapsed and the removal
      of two misfitting items resulted in a scale which conformed to the Rasch
      expectations. For validity, the scale correlated positively with parenting
      stress, and it could differentiate between parents of children diagnosed with
      learning/behaviour problems and those attending primary schools. The internal
      consistency estimate (the Cronbach alpha) was above .70. The SNQ could be used to
      help identify the needs of families with children with developmental
      disabilities.

PMID- 20153604
TI  - 3D segmentation of coronary arteries based on advanced mathematical morphology
      techniques.
AB  - In this article, we propose an automatic algorithm for coronary artery
      segmentation from 3D X-ray data sequences of a cardiac cycle (3D-CT scan, 64
      detectors, 10 phases). This method is based on recent mathematical morphology
      techniques (some of them being extended in this article). It is also guided by
      anatomical knowledge, using discrete geometric tools to fit on the artery shape
      independently from any perturbation of the data. The application of the method on
      a validation dataset (60 images: 20 patients in 3 phases) led to 90% correct (and
      automatically obtained) segmentations, the 10% remaining cases corresponding to
      images where the SNR was very low.

PMID- 20153605
TI  - The effect of injectable calcium phosphate cement on bone anchorage of titanium
      implants: an experimental feasibility study in dogs.
AB  - Calcium phosphate has high osteotransductive potential. The injectable form of
      calcium phosphate cement (ICAP) can be used as an adjunctive supportive agent for
      dental implants. The aim of this study was to assess the effect of an ICAP on the
      reverse torque resistance of titanium implants. Two implant beds (total 24) were
      prepared in each proximal tibia of 6 beagles. ICAP was injected into one of
      prepared implant beds (test) and the implant was inserted. The next implant was
      inserted without ICAP to serve as control. Three dogs were killed after 2 weeks
      and 3 after 12 weeks. Retrieved implants were subjected to reverse torque test.
      Results were analyzed with Student's t-test. Scanning electron microscope (SEM)
      was used for further evaluation. Mean torque values in 2-week healed implants
      were 52.48 N cm and 50.57 N cm for test and control implants, respectively
      (p=0.4). 12-week healed implants showed 81.61 N cm and 76.71 N cm for test and
      control implants, respectively (p=0.14). Results indicated no statistical
      difference between test and control implants for either healing time. SEM images
      of tested samples revealed close contact between the bone-ICAP-titanium surface.
      ICAP must be tested on further developed experimental models.

PMID- 20153606
TI  - Whole-genome linkage scan for epilepsy-related photosensitivity: a mega-analysis.
AB  - Photoparoxysmal response (PPR) is considered to be a risk factor for idiopathic
      generalised epilepsy (IGE) and it has a strong genetic basis. Two genome-wide
      linkage studies have been published before and they identified loci for PPR at
      6p21, 7q32, 13q13, 13q31 and 16p13. Here we combine these studies, augmented with
      additional families, in a mega-analysis of 100 families. Non-parametric linkage
      analysis identified three suggestive peaks for photosensitivity, two of which are
      novel (5q35.3 and 8q21.13) and one has been found before (16p13.3). We found no
      evidence for linkage at four previously detected loci (6p21, 7q32, 13q13 and
      13q31). Our results suggest that the different family data sets are not linked to
      a shared locus. Detailed analysis showed that the peak at 16p13 was mainly
      supported by a single subset of families, while the peaks at 5q35 and 8q21 had
      weak support from multiple subsets. Family studies clearly support the role of
      PPR as a risk factor for IGE. This mega-analysis shows that distinct loci seem to
      be linked to subsets of PPR-positive families that may differ in subtle clinical
      phenotypes or geographic origin. Further linkage studies of PPR should therefore
      include in-depth phenotyping to make appropriate subsets and increase genetic
      homogeneity.

PMID- 20153607
TI  - P50 gating in deficit and nondeficit schizophrenia.
AB  - Dysfunctional auditory sensory processing has generally been found in
      schizophrenia and it has been suggested that these deficits might be related to
      clinical and psychosocial variables. The present study included P50 recordings
      using a simple-paired click auditory evoked potential paradigm in sixty patients
      with deficit schizophrenia (DS), sixty patients with nondeficit schizophrenia
      (NDS), and sixty comparison subjects. The Schedule for the Deficit Syndrome was
      used to categorize patients as DS or NDS. The two patient groups did not differ
      in clinical variables, except for higher negative dimension and lower community
      outcome scores in DS than in NDS patients. There were no differences in P50
      ratios between deficit and nondeficit subgroups; compared with normal subjects
      both groups of schizophrenia patients showed impaired P50 ratios (p<0.0001). This
      ratio appears to be independent of positive and negative symptoms. However,
      impairment in P50 gating correlated with poorer community outcome. The data
      document the existence of early auditory sensory processing abnormalities in DS
      and NDS, and might suggest that common neuronal network abnormalities underlie
      both forms of schizophrenia. Deficient P50 gating may be associated with impaired
      functional outcome in schizophrenia.

PMID- 20153609
TI  - Three-pulse spin echo signals from quadrupolar nuclei in magnetic materials.
AB  - The time evolutions of the three-pulse spin echo signals from quadrupolar nuclei
      (63)Cu and (53)Cr in ferromagnetic CuCr(2)S(4):Sb have been investigated at the
      temperature T=77K. The experimental results were well explained by the developed
      theory of the time evolutions of the three-pulse echoes. The main assumption of
      this theory is the assumption that the temporal fluctuations in the electron
      magnetization lead to the fluctuations in the hyperfine and quadrupole
      interaction Hamiltonians.

PMID- 20153608
TI  - Differential fractional anisotropy abnormalities in adolescents with ADHD or
      schizophrenia.
AB  - Schizophrenia and Attention-Deficit/Hyperactivity Disorder (ADHD) are associated
      with similar deficits in working memory, attention, and inhibition. Both
      disorders also involve abnormalities of white matter integrity, possibly
      reflecting neural communication disruptions. There are likely some regional white
      matter abnormalities that underlie the common cognitive impairment, though also
      some regional abnormalities unique to each disorder. We used diffusion tensor
      imaging (DTI) to compare white matter integrity, as indicated by fractional
      anisotropy (FA), in adolescents with schizophrenia (n=15) or ADHD (n=14) and
      healthy controls (n=26). Schizophrenia patients had uniquely low FA, relative to
      the other two groups, in bilateral cerebral peduncles, anterior and posterior
      corpus callosum, right anterior corona radiata, and right superior longitudinal
      fasciculus. ADHD patients had uniquely high FA in left inferior and right
      superior frontal regions. Both clinical groups had lower FA than controls in left
      posterior fornix. The two disorders generally demonstrated distinct patterns of
      abnormal connectivity suggesting that common cognitive and behavioral deficits
      derive from distinct sources, though the posterior fornix may be involved in both
      disorders. Schizophrenia was associated with abnormally low FA in widespread
      circuitry indicative of general connectivity disruptions, whereas ADHD was
      associated with abnormally high FA in frontal networks that may indicate impaired
      branching of fibers.

PMID- 20153610
TI  - Cerium binding activity of different pectin compounds in aqueous solutions.
AB  - Cerium binding activity of different water soluble pectin compounds varying
      according to their degree of esterification and insoluble calcium pectate beads
      in aqueous solution was studied in a batch sorption system. The cerium uptake by
      all pectin compounds was highest within the pH range from 4.0 to 6.0. The binding
      capacities and rates of cerium ions by pectin compounds were evaluated. The
      Langmuir, Freundlich and BET sorption models were applied to describe the
      isotherms and constants. Sorption isothermal data could be well interpreted by
      the Langmuir equation. The results obtained through the study suggest that pectin
      compounds are favorable sorbents. The largest amount of cerium ions is bound by
      pectin with the degree of esterification close to zero. Therefore, it can be
      concluded that low esterified pectins are more effective substances for
      elimination of cerium ions from aqueous disposals.

PMID- 20153611
TI  - Three new freshwater species of centrohelid heliozoans: Acanthocystis crescenta
      sp. nov., A. kirilli sp. nov., and Choanocystis minima sp. nov.
AB  - Three new species of centrohelid heliozoans Acanthocystis crescenta, A. kirilli,
      and Choanocystis minima from two freshwater lakes of Valamo Island (North-Western
      Russia) were studied using light- and scanning electron microscopy. The main
      apomorphy of A. kirilli are slightly branched radial scales. Acanthocystis
      crescenta has characteristic radial scales with crescent-like structures on their
      tips. Cell diameter of these two species does not exceed 10 microm. Radial scales
      of C. minima have truncated tips and lack apical teeth; plate scales of this
      species are oviform, without lateral notches or central rib. The latter organism
      is the smallest heliozoan species known; the diameter of its body is about 3
      microm. The possible domination of small heliozoans in the cryptic diversity of
      centrohelids is discussed.

PMID- 20153612
TI  - The direct economic cost of pharmacologically-treated diabetes in Italy-2006. The
      ARNO observatory.
AB  - AIMS/HYPOTHESIS: To estimate the prevalence and the direct cost of
      pharmacologically-treated diabetes in Italy. METHODS: The ARNO observatory
      database, containing the 20-year medical prescriptions of over 10 million Italian
      people, was used. Ten-year longitudinal data were available in 22 Local Health
      Districts (LHD). Subjects were classified as having diabetes when prescribed
      glucose-lowering drugs (oral agents or insulin) (311,979 individuals in 2006).
      The direct cost was calculated as the sum of drug use, financial compensation by
      LHD for the inpatient (hospital DRG) and outpatient activities (consultations,
      laboratory tests, radiology, etc.), all regulated by government contracts.
      Individuals with diabetes were compared with pharmacologically-treated subjects
      without diabetes, pair-matched for age, sex and general practitioner. RESULTS: In
      the 10-year period, the prevalence of pharmacologically-treated diabetes
      increased from 3.08% to 4.45% (P for trend, <0.001). The average pro capita cost
      totaled ?2,589 in 2006 (95% confidence interval (CI), 2,584-2,594), corresponding
      to a rate ratio vs. no-diabetes of 1.54 (95% CI, 1.50-1.56). The cost of drugs
      was ? 827 (rate ratio, 1.80 vs. no-diabetes; 95% CI, 1.79-1.82), that of service
      use, ? 488 (rate ratio, 1.07 (0.93-1.25). Only 20% of the pharmaceutical cost was
      due to glucose-lowering drugs, a percentage stable through the years. The cost of
      any hospital admission, as defined by DRGs, was independent of diabetes, but the
      overall cost was much higher in diabetes due to much higher admission rates.
      Cardiovascular complications and renal failure accounted for the large majority
      of excess hospital cost. CONCLUSION: The direct economic burden of
      pharmacologically-treated diabetes on the National Health System is very high,
      due to the growing prevalence of disease and the cost of complications.

PMID- 20153613
TI  - Cardiovascular events in patients with antiphospholipid antibodies: strategies of
      prevention.
AB  - Antiphospholipid antibodies are a heterogeneous group of auto-antibodies against
      phospholipids-binding proteins. The antiphospholipid syndrome is an autoimmune
      disorder characterized by the clinical association of antiphospholipid antibodies
      with a condition of hypercoagulability that can affect any blood vessel.
      Involvement of larger vessels, such as arteries or veins, manifests in the form
      of thrombosis or thromboembolism, whereas involvement of small vessels manifests
      as thrombotic micro-angiopathy. The antiphospholipid syndrome is also
      characterized by the presence of recurrent fetal loss. Patients who are
      persistently positive for antiphospholipid tests, and who have an arterial
      thrombosis or venous thrombosis history, are at increased risk of recurrence.
      Oral anticoagulant therapy is the mainstay of treatment for the thrombotic
      manifestations of the syndrome. Therapy with anticoagulant drugs should be long
      term. On the other hand, although the thromboembolic potential of
      antiphospholipid antibodies has been well documented, there is still no general
      consensus on the prophylactic treatment of antiphospholipid antibodies carriers
      who have never developed vascular/obstetric manifestations. The effect of primary
      prophylaxis in antiphospholipid antibodies positive individuals is not well known
      and no evidence-based recommendations exist for thrombosis prevention in these
      individuals. However, the presence of risk factors for thrombosis increases the
      risk of first event of antiphospholipid antibodies positive patients. In
      conclusion, there is still much to learn on primary prophylaxis of asymptomatic
      antiphospholipid antibodies carriers. Hopefully, evidence-based guidelines will
      be available in the future.

PMID- 20153614
TI  - Plasma adiponectin concentration is strongly associated with VLDL-TG catabolism
      in postmenopausal women.
AB  - BACKGROUND AND AIMS: To investigate associations between plasma adiponectin
      concentration and very-low density lipoprotein-triglyceride (VLDL-TG) secretion
      and catabolism in postmenopausal women. METHODS AND RESULTS: This cross-sectional
      study included 30 postmenopausal women. Plasma adiponectin concentration was
      measured by ELISA. Insulin sensitivity was assessed by a 2-h euglycemic
      hyperinsulinemic clamp. Fasting plasma glucose (FPG) and 2-hour plasma glucose
      (2hPG) were measured during an oral glucose tolerance test. The calculation of
      VLDL-TG fractional catabolic rate (FCR) and VLDL-TG total secretion rate (TSR)
      were based on the monoexponential decrease of TG-[2H5] glycerol values obtained
      following the administration of a 2H5-glycerol bolus. Plasma adiponectin
      concentration was negatively associated with VLDL-TG TSR (r=-0.50; p=0.005) and
      positively associated with VLDL-TG FCR (r=0.54; p<0.002). This latter association
      remained significant after further adjustments for insulin sensitivity, visceral
      adipose tissue, HDL-C, FPG and 2hPG concentrations. In a multivariate model
      including adiponectin, insulin sensitivity and 2hPG, plasma adiponectin level was
      the strongest correlate of VLDL-TG FCR. CONCLUSIONS: Elevated plasma adiponectin
      concentration is associated with a favourable VLDL-TG metabolism.

PMID- 20153615
TI  - Nutrient intake in relation to central and overall obesity status among elderly
      people living in the Mediterranean islands: the MEDIS study.
AB  - BACKGROUND AND AIM: The aim of the present work was to evaluate the relationship
      between energy-generating nutrients and the presence of central and overall
      obesity after correcting for socio-demographic, lifestyle and clinical
      characteristics, among healthy elders. METHODS AND RESULTS: During 2005-2007, 553
      elderly men and 637 elderly women (mean age 74+/-7years) from eight Mediterranean
      islands in Greece and Cyprus, were enrolled. The retrieved information included
      demographic, bio-clinical and dietary characteristics. MedDietScore assessed
      adherence to the Mediterranean dietary pattern. The prevalence of obesity was 27%
      in males and 39% in females (p<0.001), while 73% of males and 87% of females had
      central obesity. The prevalence of diabetes, hypercholesterolemia and
      hypertension was higher in the obese than in the non-obese participants (p<0.01).
      After adjusting for various confounders, a 1% increase in carbohydrate
      consumption was associated with a 12% (95% CI 0.78-0.99) lower likelihood of
      having central obesity, while a 1% increase in carbohydrate and protein
      consumption was associated with a 14% (95% CI 0.78-0.95) and 16% (95% CI 0.72
      0.97) lower likelihood of being obese, respectively. Vegetable protein was found
      to be associated with a 15% (95% CI 0.77-0.93) lower likelihood of being obese
      while, only low glycemic index carbohydrates seem to be associated with a 6% (95%
      CI 0.90-0.98) lower likelihood of having central obesity. CONCLUSIONS: The
      presented findings suggest that a diet high in carbohydrates and vegetable
      protein is associated with a lower likelihood of being obese and may help elderly
      people to preserve normal weight.

PMID- 20153616
TI  - Body fat distribution and C-reactive protein--a principal component analysis.
AB  - BACKGROUND AND AIMS: To assess, using principal component analysis, the
      independent associations of general, central and peripheral subcutaneous fat with
      high-sensitivity C-reactive protein (hs-CRP), in men and women from the general
      population. METHODS AND RESULTS: We studied 833 women and 486 men, randomly
      selected from the non-institutionalized population of Porto, Portugal, with
      information on hs-CRP (<=10 mg/l) and anthropometrics (1999-2003). Body mass
      index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and a skinfold
      composite index to estimate the proportion of arm subcutaneous fat (PSFA), were
      ascertained by trained personnel. Beta regression coefficients were obtained from
      generalized linear models with adjustment for the main confounders. Direct
      associations were found between BMI, WC, WHR and hs-CRP. PSFA was inversely
      associated with hs-CRP in women (beta=-0.080, p-trend=0.010). Since the
      anthropometric measures were strongly correlated, we used principal component
      analysis to identify new independent anthropometric factors. The first one,
      representing a generalized fat distribution (high BMI and WC), was directly
      associated with hs-CRP (beta=0.226, p-trend<0.001 in women; beta=0.138, p
      trend=0.002 in men). The second factor, characterized by a high PSFA, showed an
      inverse association with hs-CRP in women (beta=-0.071, p-trend=0.048). The third
      factor, representing a central pattern of fat distribution (low BMI, but high WC
      and high WHR), was directly associated with hs-CRP in men (beta=0.090, p
      trend=0.005). CONCLUSION: A central pattern of fat distribution is directly
      associated with hs-CRP levels in men, while a high proportion of peripheral
      subcutaneous fat seems to be inversely associated with hs-CRP, but only in women.

PMID- 20153617
TI  - Abdominal subcutaneous adipose tissue morphology in a patient with a dominant
      negative mutation (P467L) in the nuclear receptor peroxisome proliferator
      activated receptor-gamma (PPARG) gene.

PMID- 20153619
TI  - Low-fat dairy consumption reduces systolic blood pressure, but does not improve
      other metabolic risk parameters in overweight and obese subjects.
AB  - BACKGROUND AND AIMS: Epidemiological studies have indicated a negative relation
      between low-fat dairy consumption and the metabolic syndrome. However, evidence
      from intervention studies is scarce. Our aim was to investigate the effects of
      daily consumption of low-fat dairy products on metabolic risk parameters in
      overweight and obese men and women. METHODS AND RESULTS: Thirty-five healthy
      subjects (BMI>27 kg/m(2)) consumed low-fat dairy products (500 mL low-fat milk
      and 150 g low-fat yogurt) or carbohydrate-rich control products (600 mL fruit
      juice and 3 fruit biscuits) daily for 8 weeks in random order. Compared with the
      control period, systolic blood pressure was decreased by 2.9 mm Hg (95%
      confidence interval (CI), -5.5 to -0.3 mm Hg; P=0.027), while the difference in
      diastolic blood pressure did not reach statistical significance (95% CI, -3.4 to
      0.3 mm Hg; P=0.090). Low-fat dairy consumption decreased HDL-cholesterol
      concentrations by 0.04 mmol/L (95% CI, -0.07 to -0.01 mmol/L; P=0.021) and apo A
      1 concentrations by 0.04 g/L (95% CI, -0.07 to -0.01 g/L; P=0.016) compared with
      control. Serum total cholesterol, LDL-cholesterol, apo B, triacylglycerols, non
      esterified fatty acids, glucose, insulin, C-reactive protein and plasminogen
      activator inhibitor-1 were unchanged. CONCLUSION: We conclude that in overweight
      and obese subjects, daily intake of low-fat dairy products for 8 weeks decreased
      systolic blood pressure, but did not improve other metabolic risk factors related
      to the metabolic syndrome.

PMID- 20153620
TI  - Pisiferdiol and pisiferic acid isolated from Chamaecyparis pisifera activate
      protein phosphatase 2C in vitro and induce caspase-3/7-dependent apoptosis via
      dephosphorylation of Bad in HL60 cells.
AB  - Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates and
      regulates apoptosis, stress response and growth-related pathways. In the course
      of screening for PP2C activators from natural sources, we isolated abietane-type
      diterpenes, pisiferdiol and pisiferic acid from Chamaecyparis pisifera.
      Pisiferdiol having a unique seven-membered ring showed more specific PP2C
      activation activity (1.3-fold at 100 microM) than pisiferic acid having a normal
      six-membered ring and oleic acid, which is known to activate PP2C. Pisiferdiol
      and pisiferic acid showed mixed-type activation with respect to alpha-casein, and
      this differed from the non-competitive activation of oleic acid in vitro. In
      vivo, the cytotoxicity of pisiferdiol toward human promyelocytic leukemia cell
      line HL60 with an IC(50) value of 18.3 microM was 2-fold and 7-fold stronger than
      those of pisiferic acid and oleic acid, and pisiferdiol induced apoptosis through
      a caspase 3/7-dependent mechanism involving the dephosphorylation of Bad(1),
      which is a PP2C substrate. We thus conclude that pisiferdiol and pisiferic acid
      are novel PP2C activators, and the more specific activator, pisiferdiol, may be a
      useful chemical probe to study PP2C-mediated signaling pathways, and a lead
      compound for pharmaceutical agents.

PMID- 20153618
TI  - Pericardial fat is associated with carotid stiffness in the Multi-Ethnic Study of
      Atherosclerosis.
AB  - BACKGROUND AND AIMS: Arterial stiffness is a prominent feature of vascular aging
      and a risk factor for cardiovascular disease (CVD). Fat around the heart and
      blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness
      via a local paracrine effect of adipose tissue on the surrounding vasculature.
      Thus, we determined the association between Pfat and carotid stiffness in 5770
      participants (mean age 62 years, 53% female, 25% African American, 24% Hispanic,
      and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis. METHODS AND
      RESULTS: Pfat was measured by computed tomography, and ultrasonography of the
      common carotid artery was used to calculate the distensibility coefficient (DC)
      and Young's modulus (YM). Lower DC and higher YM values indicate stiffer
      arteries. Pfat quartile was highly associated with demographic, behavioral,
      anthropometric, hemodynamic, metabolic, and disease variables in both men and
      women. After adjusting for height, clinical site, CVD risk factors, and
      medications, a 1 standard deviation (41.91 cm(3)) increment in Pfat was
      associated with a 0.00007+/-0.00002 1/mm Hg lower DC (p=0.0002) in men and a
      48.1+/-15.1 mm Hg/mm higher YM in women (p=0.002). Additional adjustment for C
      reactive protein, coronary artery calcification, and carotid intima-media
      thickness had only modest effects. More importantly, adjusting for body mass
      index and waist circumference did not significantly change the overall results.
      CONCLUSION: Higher Pfat is associated with higher carotid stiffness, independent
      of traditional CVD risk factors and obesity.

PMID- 20153621
TI  - Antisecretory, antioxidative and antiapoptotic effects of montelukast on pyloric
      ligation and water immersion stress induced peptic ulcer in rat.
AB  - In the present study, we tried to explore the mechanism of montelukast as an
      antiulcerogenic agent in pyloric ligation (PL) and water immersion stress (WIS)
      induced peptic ulcer. The ameliorative effects of montelukast (5, 10, and 20
      mg/kg, p.o.) on gastric volume and total acidity were studied in PL model. We
      have investigated the alteration in the ulcerative index, thiobarbituric acid
      reactive substances, reduced glutathione, activity of myeloperoxidase, and total
      calcium level in both models. Estimation of DNA fragmentation by gel
      electrophoresis was also performed. Medium and higher doses of montelukast showed
      significant (p<0.05) ameliorative potential on all the above parameters as
      compared with omeprazole treated group. DNA fragmentation pattern clearly
      indicated the antiapoptotic effect of montelukast in preventing mucosal erosion
      in both models. Hence, the gastroprotective effect of montelukast may be
      attributed to its antisecretory, antioxidative along with its antiapoptotic
      effect.

PMID- 20153622
TI  - Host-microbe interactions in the developing zebrafish.
AB  - The amenability of the zebrafish to in vivo imaging and genetic analysis has
      fueled expanded use of this vertebrate model to investigate the molecular and
      cellular foundations of host-microbe relationships. Study of microbial encounters
      in zebrafish hosts has concentrated on developing embryonic and larval stages,
      when the advantages of the zebrafish model are maximized. A comprehensive
      understanding of these host-microbe interactions requires appreciation of the
      developmental context into which a microbe is introduced, as well as the effects
      of that microbial challenge on host ontogeny. In this review, we discuss how in
      vivo imaging and genetic analysis in zebrafish has advanced our knowledge of host
      microbe interactions in the context of a developing vertebrate host. We focus on
      recent insights into immune cell ontogeny and function, commensal microbial
      relationships in the intestine, and microbial pathogenesis in zebrafish hosts.

PMID- 20153623
TI  - Vitamin E status and metabolism in adult and aged aryl hydrocarbon receptor null
      mice.
AB  - The aryl hydrocarbon receptor (AhR) is involved in regulation of mechanisms for
      detoxification of xenobiotics, as well as vitamin A metabolism. Vitamin E is a
      fat-soluble nutrient whose metabolism is initialized via the cytochrome P450
      system. Thus, AhR absence could alter hepatic regulation of alpha-tocopherol
      metabolism. To test this hypothesis, we assessed vitamin E status in adult (2-5
      m) and old (21-22 m), wild-type and AhR-null mice. Plasma alpha-tocopherol
      concentrations in AhR-null mice (2.3+/-1.2 MUmol/L, n=19) were lower than those
      of wild-type mice (3.2+/-1.2, n=17, P=.0131); those in old mice (3.2+/-1.2, n=20)
      were higher than those of adults (2.2+/-1.0, n=16, P=.0075). Hepatic alpha
      tocopherol concentrations were not different between genotypes, but were nearly
      double in old (32+/-8 nmol/g, n=20) as compared with adult mice (17+/-2, n=16,
      P<.0001). Hepatic Cyp3a concentrations in AhR-null mice were greater than those
      in wild-type mice (P=.0011). Genotype (P=.0047), sex (P<.0001) and age (P<.0001)
      were significant modifiers of liver alpha-tocopherol metabolite (alpha-CEHC)
      concentrations. In general, Cyp3a concentrations correlated with hepatic alpha
      tocopherol (r=0.3957, P<.05) and alpha-CEHC (r=0.4260, P<.05) concentrations.
      Since there were no significant genotype differences in the hepatic alpha- or
      gamma-tocopherol concentrations, AhR-null mice did not have dramatically altered
      vitamin E metabolism. Since they did have higher hepatic alpha-CEHC
      concentrations, these data suggest metabolism was up-regulated in the AhR-null
      mice in order to maintain the hepatic tocopherol concentrations similar to those
      of wild-type mice.

PMID- 20153624
TI  - alpha-Tocopherol is an effective Phase II enzyme inducer: protective effects on
      acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal
      pigment epithelial cells.
AB  - Vitamin E has long been identified as a major lipid-soluble chain-breaking
      antioxidant in mammals. alpha-Tocopherol is a vitamin E component and the major
      form in the human body. We propose that, besides its direct chain-breaking
      antioxidant activity, alpha-tocopherol may exert an indirect antioxidant activity
      by enhancing the cell's antioxidant system as a Phase II enzyme inducer. We
      investigated alpha-tocopherol's inducing effect on Phase II enzymes and its
      protective effect on acrolein-induced toxicity in a human retinal pigment
      epithelial (RPE) cell line, ARPE-19. Acrolein, a major component of cigarette
      smoke and also a product of lipid peroxidation, at 75 MUmol/L over 24 h, caused
      significant loss of ARPE-19 cell viability, increased oxidative damage, decreased
      antioxidant defense, inactivation of the Keap1/Nrf2 pathway, and mitochondrial
      dysfunction. ARPE-19 cells have been used as a model of smoking- and age-related
      macular degeneration. Pretreatment with alpha-tocopherol activated the Keap1/Nrf2
      pathway by increasing Nrf2 expression and inducing its translocation to the
      nucleus. Consequently, the expression and/or activity of the following Phase II
      enzymes increased: glutamate cysteine ligase, NAD(P)H:quinone oxidoreductase 1,
      heme-oxygenase 1, glutathione S-transferase and superoxide dismutase; total
      antioxidant capacity and glutathione also increased. This antioxidant defense
      enhancement protected ARPE-19 cells from an acrolein-induced decrease in cell
      viability, lowered reactive oxygen species and protein oxidation levels, and
      improved mitochondrial function. These results suggest that alpha-tocopherol
      protects ARPE-19 cells from acrolein-induced cellular toxicity, not only as a
      chain-breaking antioxidant, but also as a Phase II enzyme inducer.

PMID- 20153626
TI  - High sensitive detection of cancer cell with a folic acid-based boron-doped
      diamond electrode using an AC impedimetric approach.
AB  - An electrochemical impedance method at a fixed frequency (10Hz) is used to detect
      folate receptor-rich cancer cells with the interaction between folic acid
      immobilized on gold nanoparticles deposited on boron-doped diamond (BDD)
      electrode surface and its receptor over-expressed on cancer cell membrane without
      additional labeling. Experimental results have shown that the BDD electrode
      modified with folic acid can clearly denote folate receptor-rich cancer cells,
      such as HeLa cells, at a concentration down to 10 cells mL(-1). The high
      sensitivity of BDD electrode is resulted from the change of field effect and
      surface charge density of BDD after cancer cells attachment. The BDD electrodes
      can be regenerated with 0.1M citric acid/glycine/HC1 at pH 3.0 and used seven
      times again. Therefore, electrochemical technique with BDD electrode has been
      introduced for cancer cells detection and a simple method to detect folate
      receptor-rich cancer cells without additional labeling has been developed.

PMID- 20153625
TI  - Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with
      implications for colon cancer chemoprevention.
AB  - The nuclear vitamin D receptor (VDR) mediates the actions of 1,25
      dihydroxyvitamin D(3) (1,25D) to regulate gene transcription. Recently, the
      secondary bile acid, lithocholate (LCA), was recognized as a novel VDR ligand.
      Using reporter gene and mammalian two-hybrid systems, immunoblotting, competitive
      ligand displacement and quantitative real-time PCR, we identified curcumin (CM),
      a turmeric-derived bioactive polyphenol, as a likely additional novel ligand for
      VDR. CM (10(-5) M) activated transcription of a luciferase plasmid containing the
      distal vitamin D responsive element (VDRE) from the human CYP3A4 gene at levels
      comparable to 1,25D (10(-8) M) in transfected human colon cancer cells (Caco-2).
      While CM also activated transcription via a retinoid X receptor (RXR) responsive
      element, activation of the glucocorticoid receptor (GR) by CM was negligible.
      Competition binding assays with radiolabeled 1,25D confirmed that CM binds
      directly to VDR. In mammalian two-hybrid assays employing transfected Caco-2
      cells, CM (10(-5) M) increased the ability of VDR to recruit its heterodimeric
      partner, RXR, and steroid receptor coactivator-1 (SRC-1). Real-time PCR studies
      revealed that CM-bound VDR can activate VDR target genes CYP3A4, CYP24, p21 and
      TRPV6 in Caco-2 cells. Numerous studies have shown chemoprotection by CM against
      intestinal cancers via a variety of mechanisms. Small intestine and colon are
      important VDR-expressing tissues where 1,25D has known anticancer properties that
      may, in part, be elicited by activation of CYP-mediated xenobiotic detoxification
      and/or up-regulation of the tumor suppressor p21. Our results suggest the novel
      hypothesis that nutritionally-derived CM facilitates chemoprevention via direct
      binding to, and activation of, VDR.

PMID- 20153627
TI  - In situ passive solid-phase adsorption of micro-algal biotoxins as a monitoring
      tool.
AB  - Laboratory and field studies of the passive solid-phase adsorption toxin tracking
      (SPATT) method have been carried out around the world. A wide range of marine
      micro-algal toxins have been detected and the potential of the method to provide
      reliable, sensitive, time-integrated sampling to monitor the occurrence of toxic
      algal bloom events has been demonstrated. The method has several important
      advantages over current phytoplankton and shellfish monitoring methods. Trials of
      various adsorption substrates have been carried out and the best candidates have
      been selected for the lipophilic marine biotoxin groups; however, research
      continues to locate suitable substrates for the more polar water-soluble
      compounds such as domoic acid and the saxitoxins. The technique has also been
      successfully applied to the detection of a range of freshwater cyanobacterial
      toxins.

PMID- 20153628
TI  - Paramutation in maize: RNA mediated trans-generational gene silencing.
AB  - Paramutation involves trans-interactions between alleles or homologous sequences
      that establish distinct gene expression states that are heritable for
      generations. It was first described in maize by Alexander Brink in the 1950s,
      with his studies of the red1 (r1) locus. Since that time, paramutation-like
      phenomena have been reported in other maize genes, other plants, fungi, and
      animals. Paramutation can occur between endogenous genes, two transgenes or an
      endogenous gene, and transgene. Recent results indicate that paramutation
      involves RNA-mediated heritable chromatin changes and a number of genes
      implicated in RNAi pathways. However, not all aspects of paramutation can be
      explained by known mechanisms of RNAi-mediated transcriptional silencing.

PMID- 20153630
TI  - Common predisposition alleles for moderately common cancers: bladder cancer.
AB  - Bladder cancer is the 5th commonest cancer and two major risk factors are smoking
      and occupational chemical exposure. There is also evidence of a genetic component
      to its aetiology. Candidate gene studies have mostly focused on genes involved in
      adduct metabolism and DNA repair, including a recent consortium-based meta
      analysis. Recently, two genome-wide association studies in bladder cancer have
      been published and a third is awaited with interest. These first two studies have
      identified three SNPs of genome-wide significance, two located within the 8q24
      'gene desert'. These SNPs are positioned near or within loci of genes potentially
      implicated in cancer predisposition, namely MYC, TP63 and PSCA, although the
      functional significance of this is as yet unclear.

PMID- 20153631
TI  - Limited impact of free ammonia on Nitrobacter spp. inhibition assessed by
      chemical and molecular techniques.
AB  - Free ammonia has long been identified as a nitrite oxidation inhibitor. However,
      past attempts to use this compound to eliminate nitrite oxidation and thereby
      promote more efficient nitrogen removal strategies during biological wastewater
      treatment have often failed. Additionally, contradictory results exist in the
      literature where direct measurements of free ammonia inhibition of nitrite
      oxidation have been reported. In this study, suspended biomass samples (nitrifier
      enriched activated sludge) were collected from a bench scale nitrification
      reactor with Nitrobacter spp. as the dominant nitrite oxidizer and subjected to
      batch respirometric experiments designed to quantify free ammonia inhibition of
      nitrite oxidization. A variety of data including ammonia, nitrite, and nitrate
      conversion rates, oxygen consumption rates, and Nitrobacter ribosomal RNA
      transcript abundance, a molecular indicator of growth activity, were used to
      assess nitrite oxidation and growth activity. Both the traditional and molecular
      activity assessments indicated that free ammonia had a limited inhibitory effect
      on Nitrobacter spp. In fact, the pH changes necessary to induce high free ammonia
      concentrations (>10mg-N/L) had a demonstrably more important inhibiting effect on
      nitrite oxidation than free ammonia. In contrast, during high ammonia oxidizing
      activity (5.3mg-N/L/h), low nitrite oxidation rates (0.2mg-N/L/h) and severely
      impaired Nitrobacter spp. growth activity, indicated by a low abundance of the
      Nitrobacter spp. ribosomal gene transcript relative to the ribosomal gene (0.08),
      were measured. The findings suggest that pH changes and ammonia oxidizing
      bacteria activity are more important factors limiting Nitrobacter spp. mediated
      nitrite oxidation, rather than the free ammonia concentration.

PMID- 20153629
TI  - New functions for an old variant: no substitute for histone H3.3.
AB  - Histone proteins often come in different variants serving specialized functions
      in addition to their fundamental role in packaging DNA. The metazoan histone H3.3
      has been most closely associated with active transcription. Its role in histone
      replacement at active genes and promoters is conserved to the single histone H3
      in yeast. However, recent genetic studies in flies have challenged its importance
      as a mark of active chromatin, and revealed unexpected insights into essential
      functions of H3.3 in the germline. With strikingly little amino acid sequence
      difference to the canonical H3, H3.3 therefore accomplishes a surprising variety
      of cellular and developmental processes.

PMID- 20153632
TI  - Vermicompost derived from different feedstocks as a plant growth medium.
AB  - This study determined feedstock effects on earthworm populations and the quality
      of resulting vermicomposts produced from different types of feedstocks using
      different vermicomposting durations. Feedstock combinations (Kitchen Paper Waste
      (KPW), Kitchen Yard Waste (KYW), Cattle Manure Yard Waste (CMY)), three durations
      of vermicomposting (45, 68 or 90 days), and two seed germination methods (with
      two concentrations of vermicompost) for radish, marigold and upland cress, served
      as the independent variables. The worms (Eisenia fetida) doubled their weight by
      day 68 in KPW and CMY vermicomposts and day 90 KPW vermicompost produced the
      greatest weight of worms. The direct seed germination method (seeding into soil
      or vermicompost-soil mixtures) indicated that KPW and KYW feedstocks decreased
      germination compared to the control, even in mature vermicompost. Seed
      germination was greater in the water extract method; however, most of the
      vermicompost extracts suppressed germination of the three seed species compared
      to the water controls. Vermicomposts from all three feedstocks increased leaf
      area and biomass compared to the control, especially in the 10% vermicompost:soil
      mix. Thus, seed germination and leaf area or plant biomass for these three
      species are contrasting vermicompost quality indicators.

PMID- 20153633
TI  - Investigation on thermochemical behaviour of low rank Malaysian coal, oil palm
      biomass and their blends during pyrolysis via thermogravimetric analysis (TGA).
AB  - This study aims to investigate the behaviour of Malaysian sub-bituminous coal
      (Mukah Balingian), oil palm biomass (empty fruit bunches (EFB), kernel shell
      (PKS) and mesocarp fibre (PMF)) and their respective blends during pyrolysis
      using thermogravimetric analysis (TGA). The coal/palm biomass blends were
      prepared at six different weight ratios and experiments were carried out under
      dynamic conditions using nitrogen as inert gas at various heating rates to ramp
      the temperature from 25 degrees C to 900 degrees C. The derivative
      thermogravimetric (DTG) results show that thermal decomposition of EFB, PMF and
      PKS exhibit one, two and three distinct evolution profiles, respectively.
      Apparently, the thermal profiles of the coal/oil palm biomass blends appear to
      correlate with the percentage of biomass added in the blends, thus, suggesting
      lack of interaction between the coal and palm biomass. First-order reaction model
      were used to determine the kinetics parameters for the pyrolysis of coal, palm
      biomass and their respective blends.

PMID- 20153634
TI  - Simultaneous sulfate reduction and copper removal by a PVA-immobilized sulfate
      reducing bacterial culture.
AB  - The effect of a sulfate reducing bacteria immobilized in polyvinyl alcohol (PVA)
      on simultaneous sulfate reduction and copper removal was investigated. Batch
      experiments were designed using central composite design (CCD) with two
      parameters, i.e. the copper concentration (10-100mg/L), and the quantity of
      immobilized SRB in culture solution (19-235 mg of VSS/L). Response surface
      methodology (RSM) was used to model the experimental data, and to identify
      optimal conditions for the maximum sulfate reduction and copper removal. Under
      optimum condition, i.e. approximately 138.5mg VSS/L of sulfate reducing bacteria
      immobilized in PVA, and approximately 51.5mg/L of copper, the maximum sulfate
      reduction rate was 1.57 d(-1) as based on the first-order kinetic equation. The
      data demonstrate that immobilizing sulfate reducing bacteria in PVA can enhance
      copper removal and the resistance of the bacteria towards copper toxicity.

PMID- 20153635
TI  - Fed-batch cultivation of Arthrospira (Spirulina) platensis: potassium nitrate and
      ammonium chloride as simultaneous nitrogen sources.
AB  - Arthrospiraplatensis was cultivated in minitanks at 13 klux, using a mixture of
      KNO(3) and NH(4)Cl as nitrogen source. Fed-batch daily supply of NH(4)Cl at
      exponentially-increasing feeding rate allowed preventing ammonia toxicity and
      nitrogen deficiency, providing high maximum cell concentration (X(m)) and high
      quality biomass (21.85 mg chlorophyll g cells(-1); 20.5% lipids; 49.8% proteins).
      A central composite design combined to response surface methodology was utilized
      to determine the relationships between responses (X(m), cell productivity and
      nitrogen-to-cell conversion factor) and independent variables (KNO(3) and NH(4)Cl
      concentrations). Under optimum conditions (15.5mM KNO(3); 14.1mM NH(4)Cl), X(m)
      was 4327 mg L(-1), a value almost coincident with that obtained with only 25.4mM
      KNO(3), but more than twice that obtained with 21.5mM NH(4)Cl. A 30%-reduction of
      culture medium cost can be estimated when compared to KNO(3)-batch runs, thus
      behaving as a cheap alternative for the commercial production of this
      cyanobacterium.

PMID- 20153636
TI  - The direct pyrolysis and catalytic pyrolysis of Nannochloropsis sp. residue for
      renewable bio-oils.
AB  - Nannochloropsis sp. (a kind of green microalga) residue was pyrolyzed without
      catalyst or with different amount of HZSM-5 catalyst in a fixed bed reactor in
      nitrogen flow. The effects of pyrolysis parameters such as temperature and
      catalyst-to-material ratio on product yields were studied. The bio-oils obtained
      were analyzed by elemental, GC-MS and FTIR analysis. The results indicated that
      the bio-oils from catalytic pyrolysis of Nannochloropsis sp. residue (BOCP) had
      lower oxygen content (19.5 wt.%) and higher heating-value (32.7 MJ kg(-1)) than
      those obtained from direct pyrolysis (BODP) which had an oxygen content of 30.1
      wt.% and heating-value of 24.6 MJ kg(-1). The BODP mainly consisted of long
      carbon chain compounds with various terminal groups (LCTG), while the BOCP mainly
      consisted of aromatic hydrocarbons. These properties of bio-oils demonstrated
      that the Nannochloropsis sp. residue can be used as a renewable energy resource
      and chemical feedstock.

PMID- 20153637
TI  - Molybdo-vanado-phosphate heteropolyanion catalyzed pulp ozonation in
      acetone/water solution. Part 1. Effect of process variables.
AB  - The effect of solvent and catalyst concentration, pH and ionic strength on ozone
      bleaching of commercial eucalyptus kraft pulp in acetone-water solution in the
      presence of Keggin-type heteropolyanion [PMo(7)V(5)O(40)](8-) (HPA-5) has been
      examined and compared with conventional (solvent/catalyst free) ozonation
      systems. The solvent content and medium acidity were found to be the principal
      factors affecting ozonation efficiency. Increase in acetone concentration from 6%
      to 60% (w/w) led to gain in pulp brightness by 20.6% and delignification degree
      by 28.4%. Within the operative pH 1-2 range required for ozonation, the increase
      in pulp brightness by 7.6% and delignification degree by 18.1% was observed with
      acidity change from pH 1 to 2. The HPA-5 concentration of 1mM was found to be
      optimal for effective pulp ozonation in acetone solution. The role of the Donnan
      effect was examined. Increase in ionic strength (cation concentration) up to 0.25
      M caused significant bleaching improvement.

PMID- 20153638
TI  - Enhanced production of longer side-chain polyhydroxyalkanoic acid with omega
      aromatic group substitution in phaZ-disrupted Pseudomonas fluorescens BM07 mutant
      through unrelated carbon source cometabolism and salicylic acid beta-oxidation
      inhibition.
AB  - The deletion of the intracellular polyhydroxyalkanoate (PHA) depolymerase gene
      (phaZ) in Pseudomonas fluorescens BM07 was found to increase more efficiently the
      levels of longer medium-chain-length (MCL) omega-aromatic monomer-units than in
      the wild-type strain when the cells were grown with a mixture of fructose and MCL
      omega-aromatic fatty acid in the presence of salicylic acid that is known as a
      beta-oxidation inhibitor in BM07 strain. When 11-phenoxyundecanoic acid was used
      as co-carbon source, the longest monomer-unit 3-hydroxy-11-phenoxyundecanoate,
      not reported in literature yet, was incorporated into the polymer chain up to
      approximately 10 mol%. An advantage of salicylic acid inhibition technique is
      that salicylic acid is not metabolized in BM07 strain, thus, the effective
      concentration of the inhibitor remaining constant throughout the cultivation. In
      conclusion, this new technique could be exploited for the enhanced production of
      side-chain modulated functional MCL-PHA with improved physicochemical properties
      in P. fluorescens BM07.

PMID- 20153639
TI  - Performance and emissions of a spark-ignited engine driven generator on biomass
      based syngas.
AB  - The emergence of biomass based energy warrants the evaluation of syngas from
      biomass gasification as a fuel for personal power systems. The objectives of this
      study were to determine the performance and exhaust emissions of a commercial 5.5
      kW generator modified for operation with 100% syngas at different syngas flows
      and to compare the results with those obtained for gasoline operation at same
      electrical power. The maximum electrical power output for syngas operation was
      1392 W and that for gasoline operation was 2451 W. However, the overall
      efficiency of the generator at maximum electrical power output for both the fuels
      were found to be the same. The concentrations of CO and NO(x) in the generator
      exhaust were lower for the syngas operation, respectively by 30-96% and 54-84%
      compared to the gasoline operation. However, the concentrations of CO(2) in the
      generator exhaust were significantly higher by 33-167% for the syngas operation.

PMID- 20153640
TI  - Expression, purification and use of the soluble domain of Lactobacillus paracasei
      beta-fructosidase to optimise production of bioethanol from grass fructans.
AB  - Microbial inulinases find application in food, pharmaceutical and biofuel
      industries. Here, a novel Lactobacillus paracasei beta-fructosidase was
      overexpressed as truncated cytosolic protein ((t)fosEp) in Escherichia coli.
      Purified (t)fosEp was thermostable (10-50 degrees C) with a pH optimum of 5; it
      showed highest affinity for bacterial levan (beta[2-6] linked fructose) followed
      by nystose, chicory inulin, 1-kestose (beta[2-1] linkages) and sucrose (K(m)
      values of 0.5, 15, 15.6, 49 and 398 mM, respectively). Hydrolysis of polyfructose
      moieties in agriculturally-sourced grass juice (GJ) with (t)fosEp resulted in the
      release of >13 mg/ml more bioavailable fructose than was measured in untreated
      GJ. Bioethanol yields from fermentation experiments with Brewer's yeast and
      GJ+(t)fosEp were >25% higher than those achieved using untreated GJ feedstock
      (36.5[+/-4.3] and 28.2[+/-2.7]mg ethanol/ml, respectively). This constitutes the
      first specific study of the potential to ferment ethanol from grass juice and the
      utility of a novel core domain of beta-fructosidase from L. paracasei.

PMID- 20153641
TI  - Solid-liquid extraction of alkali metals and organic compounds by leaching of
      food industry residues.
AB  - Leaching was studied for its application in extracting inorganic and organic
      constituents from fresh fermented grape pomace, air-dried fermented grape pomace
      and air-dried sugar beet pulp. Samples of each feedstock were leached in water at
      ambient temperature for 30 or 120 min at dry solid-to-liquid ratios of 1/20 and
      1/50 kg/L. Leaching removed 82% of sodium, 86% of potassium, and 76% of chlorine
      from sugar beet pulp, and reduced total ash concentration in air-dry fermented
      grape pomace from 8.2% to 2.9% of dry matter, 8.2% to 4.4% in fresh fermented
      grape pomace, and 12.5% to 5.4% in sugar beet pulp. Glycerol (7-11 mg/dry g),
      ethanol (131-158 mg/dry g), and acetic acid (24-31 mg/dry g) were also extracted
      from fermented grape pomace. These results indicate that leaching is a beneficial
      pretreatment step for improving the quality of food processing residues for
      thermochemical and biochemical conversion.

PMID- 20153642
TI  - Synthesis and characterization of a novel iNOS/Akt inhibitor Se,Se'-1,4
      phenylenebis(1,2-ethanediyl)bisisoselenourea (PBISe)--against colon cancer.
AB  - Our studies demonstrate that substitution of sulfur with selenium in known iNOS
      inhibitor increases the compound's potency by several folds in variety of
      different cancers cell lines tested. Hence, this approach may be used as a
      strategy to increase the efficacy of the anticancer agents.

PMID- 20153643
TI  - Optimization of 5-vinylaryl-3-pyridinecarbonitriles as PKCtheta inhibitors.
AB  - Analog 8, a 3-pyridinecarbonitrile with an (E)-2-[6-[(4-methylpiperazin-1
      yl)methyl]pyridin-2-yl]vinyl group at C-5, had an IC(50) value of 1.1 nM for the
      inhibition of PKCtheta and potently blocked the production of IL-2 in both
      stimulated murine T cells (IC(50)=34 nM) and human whole blood (IC(50)=500 nM).

PMID- 20153644
TI  - Bisleuconothine A, an eburnane-aspidosperma bisindole alkaloid from Leuconotis
      griffithii.
AB  - A new bisindole alkaloid, bisleuconothine A (1) consisting of an eburnane
      aspidosperma type skeleton, was isolated from the bark of Leuconotis griffithii.
      The structure including absolute stereochemistry was elucidated on the basis of
      2D NMR data and X-ray analysis. Bisleuconothine A (1) showed cell growth
      inhibitory activity against various human cancer cell lines.

PMID- 20153646
TI  - Indirubin derivatives as potent FLT3 inhibitors with anti-proliferative activity
      of acute myeloid leukemic cells.
AB  - Indirubin derivatives were identified as potent FLT3 tyrosine kinase inhibitors
      with anti-proliferative activity at acute myeloid leukemic cell lines, RS4;11 and
      MV4;11 which express FLT3-WT and FLT3-ITD mutation, respectively. Among several 5
      and 5'-substituted indirubin derivatives, 5-fluoro analog, 13 exhibited potent
      inhibitory activity at FLT3 (IC(50)=15 nM) with more than 100-fold selectivity
      versus 6 other kinases and potent anti-proliferative effect for MV4;11 cells
      (IC(50)=72 nM) with 30-fold selectivity versus RS4;11 cells. Cell cycle analysis
      indicated that compound 13 induced cell cycle arrest at G(0)/G(1) phase in MV4;11
      cells.

PMID- 20153645
TI  - Discovery of novel inhibitors for DHODH via virtual screening and X-ray
      crystallographic structures.
AB  - Amino-benzoic acid derivatives 1-4 were found to be inhibitors for DHODH by
      virtual screening, biochemical, and X-ray crystallographic studies. X-ray
      structures showed that 1 and 2 bind to DHODH as predicted by virtual screening,
      but 3 and 4 were found to be structurally different from the corresponding
      compounds initially identified by virtual screening.

PMID- 20153647
TI  - The identification of a selective dopamine D2 partial agonist, D3 antagonist
      displaying high levels of brain exposure.
AB  - The identification of a highly selective D(2) partial agonist, D(3) antagonist
      tool molecule which demonstrates high levels of brain exposure and selectivity
      against an extensive range of dopamine, serotonin, adrenergic, histamine, and
      muscarinic receptors is described.

PMID- 20153648
TI  - Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors:
      part 1.
AB  - A series of pyrazole-based thioethers were prepared and found to be potent
      cathepsin S inhibitors. A crystal structure of 13 suggests that the thioether
      moiety may bind to the S3 pocket of the enzyme. Additional optimization led to
      the discovery of aminoethylthioethers with improved enzymatic activity and
      submicromolar cellular potency.

PMID- 20153649
TI  - Evaluation of sentinel node biopsy by combined fluorescent and dye method and
      lymph flow for breast cancer.
AB  - BACKGROUND: Conservative breast resection with subsequent sentinel lymph node
      biopsy (SNB) is an increasingly popular initial approach for the treatment of
      breast cancer due to decreased invasiveness. SNB is a shorter procedure with
      fewer side effects than more substantial surgical procedures, but it sometimes
      fails to identify metastatic disease. Therefore, a highly sensitive and
      convenient method is needed to identify sentinel lymph nodes (SLN) with a high
      probability of containing disease in SNB. We compared the combination of
      radioisotope or dye with a fluorescence compound to analyze lymph flow to
      identify targets for SNB. MATERIALS AND METHODS: We examined patients with breast
      cancer lacking metastases in the axillary lymph node (ALN). Two methods for
      targeted SNB were developed: (1) Indocyanine Green (ICG) and Patent blue were
      injected into the skin overlying the tumor and sub-areolar region just before the
      surgical procedure. (2) ICG and radiocolloid were injected into the skin
      overlying the tumor and sub-areolar region. The draining fluorescent lymphatic
      duct was visualized using a Photodynamic Eye (PDE). We removed the SLNs that were
      identified by the dye and fluorescence imaging methods. Method 1 was applied to
      113 patients undergoing SNB, and 29 patients were treated with Method 2. In our
      study, patients were grouped by lymph flow into two types: Type C demonstrated
      convergence to one lymph duct. Type S demonstrated separate lymph ducts. RESULTS:
      Using the fluorescence imaging method, 99.3% of SLNs were identified, and 3.8
      SLNs per patient were seen. The SLN identification rates for Patent blue dye and
      radiocolloid were 92.9% and 100%, respectively, while 1.9 and 2.0 SLNs per
      patient, respectively, were seen with these methods. We classified two types of
      lymph flow based on the pattern of lymphatic drainage. Type C converged to a
      single lymph duct, while Type S drained to separate ducts. Type S lymph drainage
      was seen in 29/142 patients (20.4%), and Type C drainage was found in 113/141
      patients (79.6%). Of the patients with Type S drainage, there were 4.1 SLNs per
      patient, but only 3.4 SLNs per patient were seen in individuals with Type C
      drainage. Forty cases had metastases found in the ALNs, and five of these cases
      were dye-negative and fluorescence-positive. Among these cases, the average
      number of SLNs identified was one. CONCLUSION: The combination of fluorescence
      with a visible dye is a highly sensitive method for SLN identification. When SNB
      is guided by only the dye method, there is a risk of missing appropriate SLNs in
      patients with Type S lymph drainage or weak dye staining. The use of a
      fluorescence method together with dye could increase sensitivity of detection in
      these cases. Furthermore, fluorescent methods are ideal for hospitals that cannot
      use conventional radioactive measures.

PMID- 20153650
TI  - Exploring the caves: cavins, caveolins and caveolae.
AB  - Caveolae are ampullate (flask-shaped) invaginations that are abundant in the
      plasma membrane of many mammalian cell types. Although caveolae are implicated in
      a wide range of processes including endothelial transcytosis, lipid homeostasis
      and cellular signalling, a detailed molecular picture of many aspects of their
      function has been elusive. Until recently, the only extensively characterised
      protein components of caveolae were the caveolins. Recently, data from several
      laboratories have demonstrated that a family of four related proteins, termed
      cavins 1-4, plays key roles in caveolar biogenesis and function. Salient
      properties of the cavin family include their propensity to form complexes with
      each other and their different but overlapping tissue distribution. This review
      summarises recent data on the cavins, and sets them in the context of open
      questions on the construction and function of caveolae. The discovery of cavins
      implies that caveolae might have unexpectedly diverse structural properties, in
      accord with the wide range of functions attributed to these 'little caves'.

PMID- 20153651
TI  - Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular
      activity.
AB  - A series of novel thiophene derivatives was designed, synthesized and their
      activities as competitive inhibitors of protein tyrosine phosphatase (PTPs) 1B
      (PTP1B) inhibitors were evaluated. All the compounds showed inhibitory potencies,
      and 10 of these exhibited moderate inhibitory activities with IC(50) values less
      than 10 microM. The activity of the most potent compound P28 (IC(50)=2.1 microM)
      was 15 times higher than that of the hit compound P01. Further, four
      representative compounds (P19, P22, P28, and P31) demonstrated remarkably high
      selectivities against other PTPs (e.g., PTPalpha, LAR, CD45, and TCPTP); P19
      exhibited greater than sixfold selectivity over highly homologous TCPTP. More
      importantly, these compounds are permeable to cell membranes. The treatment of
      CHO-K1 cells with P28 (10 microM) resulted in increased phosphorylation of AKT,
      which suggested extensive cellular activity of this compound. The novel chemical
      entities reported in this study could be used for overcoming the poor selectivity
      and low cellular activity of PTP1B inhibitors and might represent a starting
      point for development of therapeutic PTP inhibitors.

PMID- 20153652
TI  - Searching for multi-target antipsychotics: Discovery of orally active
      heterocyclic N-phenylpiperazine ligands of D2-like and 5-HT1A receptors.
AB  - We described herein the design, synthesis, and pharmacological evaluation of N
      phenylpiperazine heterocyclic derivatives as multi-target compounds potentially
      useful for the treatment of schizophrenia. The isosteric replacement of the
      heterocyclic ring at the biaryl motif generating pyrazole, 1,2,3-triazole, and 2
      methylimidazole[1,2-a]pyridine derivatives resulted in 21 analogues with
      different substitutions at the para-biaryl and para-phenylpiperazine positions.
      Among the compounds prepared, 4 (LASSBio-579) and 10 (LASSBio-664) exhibited an
      adequate binding profile and a potential for schizophrenia positive symptoms
      treatment without cataleptogenic effects. Structural features of this molecular
      scaffold are discussed regarding binding affinity and selectivity for D(2)-like,
      5-HT(1A), and 5-HT(2A) receptors.

PMID- 20153653
TI  - Antifungal 3,5-disubstituted furanones: From 5-acyloxymethyl to 5-alkylidene
      derivatives.
AB  - 5-Acetoxymethyl-3-(4-bromophenyl)-2,5-dihydrofuran-2-one previously described as
      highly antifungally active was found to provide the corresponding 5-methylene
      derivative via an unusual DMSO-promoted elimination of the ester group at C5
      under antifungal assay conditions. Since the latter possessed nearly the same
      antifungal effect as that originally reported for the former, the 5-acetoxymethyl
      furanone just served as a precursor of the actual antifungally active species. A
      few series of compounds with alkyloxy, aryloxy and alkylidene substituents at C5
      of the parent furanone structure were therefore prepared and evaluated. In line
      with the ease of elimination of the substituent from C5, low activities of the 5
      alkoxy compounds were observed. On the other hand, their 5-aryloxymethyl
      congeners were found to be capable of liberating the antifungally active 5
      methylene furanone into the testing medium. The antifungal effect of the 5
      alkylidene derivatives was highly sensitive to substitution of the alkylidene
      moiety; a substituent in the allylic position was necessary for a compound to
      retain high activity. Parallel evaluation of cytostatic activity showed moderate
      activities of the antifungally active derivatives against HeLa S3 and CCRF-CEM
      lines. Cell cycle analysis of CCRF-CEM cells following the treatment with 5
      methylene-3-(4-bromophenyl)-2,5-dihydrofuran-2-one revealed that this compound is
      a necrotic agent.

PMID- 20153654
TI  - Design, synthesis, and preliminary pharmacological evaluation of new
      imidazolinones as L-DOPA prodrugs.
AB  - L-DOPA, the immediate biological precursor of dopamine, is still considered the
      drug of choice in the treatment of Parkinson's disease. However, therapy with L
      DOPA is associated with a number of acute problems. With the aim to increase the
      bioavailability after oral administration, we designed a multi-protected L-DOPA
      prodrugs able to release the drug by both spontaneous chemical or enzyme
      catalyzed hydrolysis. The new compounds have been synthesized and preliminarily
      evaluated for their water solubility, log P, chemical stability, and enzymatic
      stability. The results indicate that the incorporation of the amino acidic moiety
      of L-DOPA into an imidazoline-4-one ring provides prodrugs sufficiently stable to
      potentially cross unchanged the acidic environment of the stomach, and to be
      absorbed from the intestine. They also might be able to release L-DOPA in human
      plasma after enzymatic hydrolysis. The ability of prodrugs 6a-b to increase basal
      levels of striatal DA, and influence brain neurochemistry associated with
      dopaminergic activity following oral administration, as well as the radical
      scavenging activity against DPPH for compounds 6a-b and 15a are also reported.

PMID- 20153655
TI  - Selective benzimidazole inhibitors of the antigen receptor-mediated NF-kappaB
      activation pathway.
AB  - Dysregulated antigen receptor-mediated NF-kappaB activation can contribute to
      development of autoimmunity, chronic inflammation, and malignancy. A chemical
      biology screening strategy has identified a substituted benzimidazole that
      selectively inhibits antigen receptor-mediated NF-kappaB activation without
      blocking other NF-kappaB activation pathways. A library of analogs was
      synthesized and the structure-activity relationship and metabolic stability for
      the series is presented.

PMID- 20153656
TI  - Design, synthesis and antimicrobial properties of non-hemolytic cationic alpha
      cyclopeptoids.
AB  - The synthesis and screening of neutral and cationic, linear and cyclic peptoids
      (N-alkylglycine peptidomimetics) is described. Structure-activity relationship
      studies show that the in vitro activities of the tested peptoids depend on both
      cyclization and decoration with cationic groups. The most powerful N-lysine
      cyclopeptoid derivatives showed good antifungal activity against Candida albicans
      (ATCC90029 and L21) and Candida famata (SA550, Amph B-resistant) and low
      hemolytic activity. The effects of the cyclic peptoids on membrane
      permeabilization were evaluated by the propidium iodide exclusion assay.

PMID- 20153657
TI  - Transfer of 238U, 230Th, 226Ra, and 210Pb from soils to tree and shrub species in
      a Mediterranean area.
AB  - The soil-to-plant transfer factors of natural uranium isotopes ((238)U and
      (234)U), (230)Th, (226)Ra, and (210)Pb were studied in a disused uranium mine
      located in the Extremadura region in the south-west of Spain. The plant samples
      included trees (Quercus ilex, Quercus suber, and Eucalyptus cameldulensis) and
      one shrub (Cytisus multiflorus). All of them are characteristic of Mediterranean
      environments. The activity concentrations in leaves and fruit were determined for
      the tree species at different stages of growth. For the shrub, the total above
      ground fraction was considered in three seasons. For old leaves and fruit, the
      highest activity concentrations were found in Eucalyptus cameldulensis for all
      the radionuclides studied, except in the case of (230)Th that presented similar
      activity concentrations in all of the tree species studied. In every case, the
      transfer to fruit was less than the transfer to leaves. In the shrub, the results
      depended on the season of sampling, with the highest value obtained in spring and
      the lowest in autumn. Important correlations were obtained for (238)U and (226)Ra
      between the activity ratio in soils with that in leaves or fruit.

PMID- 20153658
TI  - Xyloglucan endotransglycosylases (XETs) from germinating nasturtium (Tropaeolum
      majus) seeds: isolation and characterization of the major form.
AB  - Five forms of xyloglucan endotransglycosylase/hydrolase (XTH) differing in their
      isoelectric points (pI) were detected in crude extracts from germinating
      nasturtium seeds. Without further fractionation, all five forms behaved as
      typical endotransglycosylases since they exhibited only transglycosylating (XET)
      activity and no xyloglucan-hydrolysing (XEH) activity. They all were
      glycoproteins with identical molecular mass, and deglycosylation led to a
      decrease in molecular mass from approximately 29 to 26.5 kDa. The major enzyme
      form having pI 6.3, temporarily designated as TmXET(6.3), was isolated and
      characterized. Molecular and biochemical properties of TmXET(6.3) confirmed its
      distinction from the XTHs described previously from nasturtium. The enzyme
      exhibited broad substrate specificity by transferring xyloglucan or
      hydroxyethylcellulose fragments not only to oligoxyloglucosides and cello
      oligosaccharides but also to oligosaccharides derived from beta-(1,4)-d
      glucuronoxylan, beta-(1,6)-d-glucan, mixed-linkage beta-(1,3; 1,4)-d-glucan and
      at a relatively low rate also to beta-(1,3)-gluco-oligosaccharides. The
      transglycosylating activity with xyloglucan as donor and cello-oligosaccharides
      as acceptors represented 4.6%, with laminarioligosaccharides 0.23%, with mixed
      linkage beta-(1,3; 1,4)-d-gluco-oligosaccharides 2.06%, with beta-(1,4)-d
      glucuronoxylo-oligosaccharides 0.31% and with beta-(1,6)-d-gluco-oligosaccharides
      0.69% of that determined with xyloglucan oligosaccharides as acceptors. Based on
      the sequence homology of tryptic fragments with the sequences of known XTHs, the
      TmXET(6.3) was classified into group II of the XTH phylogeny of glycoside
      hydrolase family GH16.

PMID- 20153659
TI  - Cadaverine turnover in soybean seedlings using 15N-labelled lysine and
      cadaverine.
AB  - The synthesis and translocation of the diamine cadaverine during soybean (Glycine
      max L. Meer cv. Sakai) germination were studied using 15N-labelled lysine (the
      cadaverine precursor) and 15N-labelled cadaverine, both under light/dark (12 h/12
      h) and total dark germinating conditions. 15N-cadaverine and non-labelled
      polyamines were simultaneously detected using ionspray ionization-mass
      spectrometry. Both 15N-cadaverine and 15N-lysine were taken up by soybean. 15N
      lysine was transported to the shoot and root and converted into 15N-cadaverine,
      whereas relatively little 15N-cadaverine was formed from 15N-lysine in the
      cotyledon. The acropetal translocation of 15N-cadaverine from the cotyledon to
      the shoot seemed to predominate over basipetal transport to the root. Although no
      other 15N-derivatised polyamines were found, supplying exogenous 15N-lysine
      seemed to indirectly affect the metabolism of 14N putrescine, spermidine and
      spermine, while no significant effect was detected after supplying 15N
      cadaverine.

PMID- 20153660
TI  - A safe and reproducible anastomotic technique for minimally invasive Ivor Lewis
      oesophagectomy: the circular-stapled anastomosis with the trans-oral anvil.
AB  - OBJECTIVES: In expert hands, the intrathoracic oesophago-gastric anastamosis
      usually provides a low rate of strictures and leaks. However, anastomoses can be
      technically challenging and time consuming when minimally invasive techniques are
      used. We present our preliminary results of a standardised 25 mm/4.8mm circular
      stapled anastomosis using a trans-orally placed anvil. MATERIALS AND METHODS: We
      evaluated a prospective cohort of 37 consecutive patients offered minimally
      invasive Ivor Lewis oesophagectomy at a tertiary referral centre. The oesophago
      gastric anastomosis was created using a 25-mm anvil (Orvil, Autosuture, Norwalk,
      CT, USA) passed trans-orally, in a tilted position, and connected to a 90-cm long
      polyvinyl chloride delivery tube through an opening in the oesophageal stump. The
      anastomosis was completed by joining the anvil to a circular stapler (end-to-end
      anastomosis stapler (EEA XL) 25 mm with 4.8-mm staples, Autosuture, Norwalk, CT,
      USA) inserted into the gastric conduit. Primary outcomes were leak and stricture
      rates. RESULTS: Thirty-seven patients (mean age 65 years) with distal oesophageal
      adenocarcinoma (n=29), squamous cell cancer (n=5) or high-grade dysplasia in
      Barrett's oesophagus (n=3) underwent an Ivor Lewis oesophagectomy between October
      2007 and August 2009. The abdominal portion was operated laparoscopically in 30
      patients (81.1%). The thoracic portion was done using a muscle-sparing mini
      thoracotomy in 23 patients (62.2%) and thoracoscopic techniques in 14 patients
      (37.8%). There were no intra-operative technical failures of the anastomosis or
      deaths. Five patients had strictures (13.5%) and all were successfully treated
      with endoscopic dilations. One patient had an anastomotic leak (2.7%) that was
      successfully treated by re-operation and endoscopic stenting of the anastomosis.
      DISCUSSION: The circular-stapled anastomosis with the trans-oral anvil allows for
      an efficient, safe and reproducible anastomosis. This straightforward technique
      is particularly suited to the completely minimally invasive Ivor Lewis
      oesophagectomy.

PMID- 20153661
TI  - Bronchoscopic balloon dilatation of tracheobronchial stenosis: long-term follow
      up.
AB  - OBJECTIVES: Bronchoscopic balloon dilatation (BBD) has become a valuable tool in
      the treatment of tracheobronchial stenosis (TBS). The objective of this study was
      to assess the short- and long-term effects of BBD. METHODS: A retrospective study
      that included all patients with confirmed, symptomatic stenosis, who underwent
      BBD between 2002 and 2008. A total of 92 BBD procedures were performed in 35
      patients at our institute. Lung function studies were recorded for all patients
      before, immediately after and 1 month following the BBD. Long-term follow-up was
      for a mean of 33+/-4 months. RESULTS: All patients had initial success, including
      increased airway dimensions and symptom relief. No complications were noted
      related to BBD. Forced expiratory volume after one second (FEV(1)) was
      significantly increased after BBD (10.5%, p=0.03). These effects persisted for at
      least 1 month. Long-term follow-up, however, demonstrated the need for stent
      placement in 25 of 35 patients (71%), 210+/-91 days after BBD. Ten of 35 patients
      died 456+/-119 days after BBD due to progression of primary disease; all deaths
      were unrelated to the BBD procedures. CONCLUSIONS: BBD is a safe method that
      offers immediate symptomatic relief in both tracheal and bronchial stenosis.
      However, BBD is a temporary measure, as many patients will require definitive or
      additional treatment with laser or stent placement.

PMID- 20153662
TI  - Four-dimensional cardiac computed tomography in mitral valve endocarditis
      obstructing the left ventricle outflow tract.

PMID- 20153663
TI  - Anti-inflammatory haemoglobin scavenging monocytes are induced following coronary
      artery bypass surgery.
AB  - OBJECTIVE: Circulating monocytes may counter systemic pro-inflammatory and
      haemolytic insults through the expression and shedding of the haemoglobin
      scavenger receptor (CD163). This prospective study aims to assess the effects of
      coronary artery bypass grafting with and without cardiopulmonary bypass (CPB) on
      haemoglobin scavenging and anti-inflammatory monocyte behaviour. METHODS: Forty
      consecutive patients underwent coronary surgery using CPB (n=20) and off-pump
      (n=20) techniques. Peri-operative blood samples were taken until the fifth day
      following surgery and statistical comparison performed to baseline using group-
      and subject-based analysis. Monocyte receptor expression and plasma
      concentrations of anti-inflammatory molecules were measured by flow cytometry and
      enzyme-linked immunosorbent assay, respectively. RESULTS: Monocyte CD163
      expression was significantly elevated post-operatively in both surgical groups
      with (p=0.001) and without CPB (p=0.000) at 24-48h. By contrast, shed CD163
      (p=0.02) and haemoglobin-haptoglobin complexes (p=0.000) in plasma were only
      significantly elevated in the on-pump group at 2-4h. Subject-based analysis
      demonstrated that CPB is an independent predictor of monocyte CD163 (p=0.002) and
      plasma sCD163 (p=0.01) concentration adjusting for the measurement timing.
      Significant downregulation of the monocyte major histocompatibility complex II
      receptor was observed in both surgical groups, whereas lipopolysaccharide
      receptor (CD14) expression only declined following on-pump surgery. The anti
      inflammatory cytokine interleukin (IL)-10 was elevated post-operatively in both
      surgical groups peaking earlier in the on-pump group (2h) versus off-pump group
      (4h). The immunoregulatory IL-6 cytokine was significantly upregulated at 4h in
      both groups. CONCLUSION: Coronary artery bypass surgery induces monocyte
      associated anti-inflammatory and immunoregulatory responses. There was no
      significant difference in haemolysis although the effect on monocyte CD163 and
      plasma sCD163 concentration was significantly different between the two groups.
      Compensation for varying pro-inflammatory and haemolytic insults may explain the
      differences observed. Therapeutic strategies for inducing such desirable
      circulating monocytes may potentially improve surgical outcome and patient
      recovery.

PMID- 20153664
TI  - Effect of induction chemotherapy on lung function and exercise capacity in
      patients affected by malignant pleural mesothelioma.
AB  - OBJECTIVES: The effect of induction chemotherapy (IC) on lung function and
      exercise capacity in patients with malignant pleural mesothelioma (MPM) has not
      been largely examined. The aim of this study was to evaluate the changes in
      pulmonary function and oxygen consumption following IC in patients with MPM.
      METHODS: Between 2004 and 2009, 36 consecutive patients (mean age 62.1 + or - 1.5
      years, M/F = 25/11) were prospectively investigated. Data concerning medical
      history, histology, staging and response to chemotherapy were collected. All
      patients underwent pulmonary function test before (in the absence of pleural
      effusion) and after chemotherapy (platinum-based agent plus pemetrexed); 23 out
      of 36 patients also performed a cardiopulmonary incremental exercise test.
      RESULTS: An epithelioid histotype was documented in 88.8% of patients. A partial
      response to chemotherapy was observed in 44.5% of cases and 36.1% of patients
      experienced grade 2-3 toxicity. A significant improvement in forced expiratory
      volume in 1s (FEV(1)) (0.13 + or - 0.30 l; P = 0.01), in VO(2) peak (1.76 + or -
      2.91 ml kg(-1) min(-1); P = 0.005), in PaO(2) at rest (4.76 + or - 9.84 mmHg; P =
      0.03) and in PaO(2) at peak exercise (6.26 + or - 12.72 mmHg; P = 0.04) was
      detected. The diffusion capacity of the lung for carbon monoxide (DLCO) also
      increased (1.25 + or - 4.68 ml min(-1) mmHg(-1)), although not significantly (P =
      0.20). The stratified analysis based on the response to IC showed a significant
      improvement in FEV(1), forced vital capacity (FVC) and vital capacity (VC) (both
      absolute and percentage of predicted values) only in patients with a partial
      response. CONCLUSIONS: An improvement in lung function and exercise capacity was
      seen after IC in patients with MPM. These data suggest that IC does not
      compromise cardiopulmonary performance in this subset of patients.

PMID- 20153665
TI  - Genetic variation at the CCR5/CCR2 gene cluster and risk of psoriasis and
      psoriatic arthritis.
AB  - OBJECTIVES: Inflammation plays a major role in psoriasis (Ps). The variation at
      several genes that encode components of the inflammatory pathways have been
      linked to the risk for Ps. Our objective was to examine the association between
      Ps and three polymorphisms at the chemokine receptors CCR5 and CCR2. METHODS: A
      total of 382 Ps patients and 500 healthy controls from Spain were genotyped for
      the CCR5-32bp deletion (DeltaCCR5), the rs1799988 (CCR5 promoter), and the CCR2
      I64V (rs1799864) polymorphisms. RESULTS: Allele and genotype frequencies did not
      differ between patients and controls for any of the three polymorphisms. However,
      the frequency of the CCR2-64I carriers was significantly higher in the patients
      who developed arthritis (n=81) compared to patients without arthritis (p=0.0007).
      CONCLUSIONS: Our work suggests that the genetic variation at the CCR2/CCR5 genes
      did not contribute to the risk for Ps, but CCR2 polymorphisms could modulate the
      risk for arthritis in patients with psoriasis.

PMID- 20153666
TI  - The growth and long term survival of Acholeplasma laidlawii in media products
      used in biopharmaceutical manufacturing.
AB  - Acholeplasma laidlawii is a potential contaminant of bovine serum and has also
      been found as a contaminant in serum free cell culture media products. Anecdotal
      evidence of A. laidlawii contamination of tryptone soya broth circulated for a
      number of years before it was acknowledged that the organism could contaminate
      microbiological broth powders. The occasional occurrence of A. laidlawii in broth
      powders and possibly in powdered components of cell culture media as part of the
      normal bioburden poses a serious threat to routine pharmaceutical and
      biopharmaceutical operations where filtration is the sterilisation method of
      choice. Absence of visual evidence of contamination cannot be relied upon as
      there is variation with both organism strain and media product in the ability to
      produce turbidity. Strains of A. laidlawii which have been isolated from broth
      powders are not significantly different in temperature or media preferences from
      other strains. A. laidlawii is capable of growing to high titre at refrigeration
      and ambient temperatures in unsupplemented bacteriological sterility media or
      serum free cell culture media and can survive for prolonged periods in these
      products.

PMID- 20153667
TI  - Clinical outcome of acute leg ischaemia due to thrombosed popliteal artery
      aneurysm: systematic review of 895 cases.
AB  - OBJECTIVES: A systematic review was performed to summarise outcomes of acute
      thrombosed popliteal artery aneurysms (PAAs) treated with thrombolysis or
      thrombectomy followed by bypass. METHODS: A systematic review was conducted of
      data on acute thrombosed PAAs dated 1 January 1990 through 30 June 2008 using the
      Cochrane Library, MEDLINE and EMBASE databases. Primary endpoint was limb
      salvage; secondary endpoints were mortality and patency of the bypasses. RESULTS:
      Eight prospective studies and 25 retrospective studies with 895 patients
      presenting with acute ischaemia were included. No randomised trials were
      included. The mortality rate after surgical repair was 3.2% (95% confidence
      interval (C.I.) 1.8-4.6). The amputation rate was 14.1% (95% C.I. 11.8-16.4).
      Thrombolysis before surgery did not result in a significant reduction of the
      number of amputations, compared with surgery (thrombectomy and bypass) alone. The
      mean primary patency rates of the bypasses at 1, 3 and 5 years were 79%, 77% and
      74%, respectively, in the 'thrombolysis' group and 71% (P=0.026), 54% (P=0.164)
      and 45% (P=0.249) in the 'thrombectomy' group. No distinction could be made
      regarding secondary patency and limb-salvage rates between the groups owing to
      insufficient data. CONCLUSIONS: Preoperative and intra-operative thrombolyses
      result in a significant improvement in 1-year primary graft patency rates, but do
      not result in a significant reduction for amputations compared with surgery
      alone.

PMID- 20153668
TI  - Cryoplasty of the venous anastomosis for prevention of intimal hyperplasia in a
      validated porcine arteriovenous graft model.
AB  - OBJECTIVES: Cryoplasty combines conventional angioplasty - percutaneous
      transluminal angioplasty (PTA) - with cold thermal energy. In this animal study,
      we investigated if preventive cryoplasty could reduce intimal hyperplasia (IH) at
      the venous anastomosis. DESIGN: We investigated cryoplasty versus PTA of the
      venous anastomosis in a validated porcine, bilateral, arteriovenous graft model.
      ANIMALS AND METHODS: In 12 pigs, 24 expanded polytetrafluoroethylene (ePTFE)
      grafts were bilaterally inserted between the common carotid artery and internal
      jugular vein. Directly after surgery, one venous anastomosis was treated with
      cryoplasty at -10 degrees C, the contralateral anastomosis with conventional PTA.
      At 4 weeks, graft flow was measured, quantitative angiography was performed and
      grafts with adjacent vessels were excised for histological analysis. RESULTS: Due
      to a number of thromboses, data for paired analysis were available from eight
      pigs. Angiographic outflow vein diameter and graft blood flow were not different
      between treatment groups. Compared with the control group, IH at the venous
      anastomosis was reduced by 47% (P=0.21) and intima/media ratio was reduced by 45%
      (P=0.07) by cryoplasty. Effects were most profound in those animals that tended
      to develop most IH. CONCLUSION: Our results suggest that preventive cryoplasty of
      the venous anastomosis might help to reduce IH in those cases that develop most
      profound IH.

PMID- 20153669
TI  - The structure of the dorsal raphe nucleus and its relevance to the regulation of
      sleep and wakefulness.
AB  - Serotonergic (5-HT) cells in the rat dorsal raphe nucleus (DRN) appear in
      topographically organized groups. Based on cellular morphology, expression of
      other neurotransmitters, afferent and efferent connections and functional
      properties, 5-HT neurons of the DRN have been grouped into six cell clusters. The
      subdivisions comprise the rostral, ventral, dorsal, lateral, caudal and
      interfascicular parts of the DRN. In addition to 5-HT cells, neurons containing
      gamma-aminobutyric acid (GABA), glutamate, dopamine, nitric oxide and the
      neuropeptides corticotropin-releasing factor, substance P, galanin,
      cholecystokinin, neurotensin, somatostatin, vasoactive intestinal peptide,
      neuropeptide Y, thyrotropin-releasing hormone, growth hormone, leu-enkephalin,
      met-enkephalin and gastrin have been characterized in the DRN. Moreover, numerous
      brain areas have neurons that project to the DRN and express monoamines
      (norepinephrine, histamine), amino acids (GABA, glutamate), acetylcholine or
      neuropeptides (orexin, melanin-concentrating hormone, corticotropin-releasing
      factor and substance P) that directly or indirectly, through local circuits,
      regulate the activity of 5-HT cells. The 5-HT cells predominate along the midline
      of the rostral, dorsal and ventral subdivisions of the DRN and outnumber the non
      5-HT cells occurring in the raphe nucleus. The GABAergic and glutamatergic
      neurons are clustered mainly in the lateral and dorsal subdivisions of the DRN,
      respectively. The 5-HT(1A) receptor is located on the soma and the dendrites of 5
      HT neurons and at postsynaptic sites (outside the DRN). It is expressed, in
      addition, by non-5-HT cells of the DRN. The 5-HT(1B) receptor is located at
      presynaptic and postsynaptic sites (outside the boundaries of the DRN). It has
      been described also in the ventromedial DRN where it is expressed by non-5-HT
      cells. The 5-HT(2A) and 5-HT(2C) receptors are located within postsynaptic
      structures. At the level of the DRN the 5-HT(2A) and 5-HT(2C) receptor-containing
      cells are predominantly GABAergic interneurons and projection neurons. Within the
      boundaries of the DRN the 5-HT(3) receptor is expressed by, among others,
      glutamatergic interneurons. 5-HT(7) receptors in the DRN are not localized to
      serotonergic neurons but, at least in part, to GABAergic cells and terminals. The
      complex structure of the DRN may have important implications for neural
      mechanisms underlying 5-HT modulation of wakefulness and REM sleep.

PMID- 20153670
TI  - The role of dorsal raphe nucleus serotonergic and non-serotonergic neurons, and
      of their receptors, in regulating waking and rapid eye movement (REM) sleep.
AB  - Based on electrophysiological, neurochemical, genetic and neuropharmacological
      approaches it is currently accepted that serotonin (5-HT) functions to promote
      waking (W) and to inhibit rapid-eye movement sleep (REMS). The serotonin
      containing neurons of the dorsal raphe nucleus (DRN) provide part of the
      serotonergic innervation of the telencephalon, diencephalon, mesencephalon and
      rhombencephalon of laboratory animals and man. The DRN has been subdivided into
      several clusters on the basis of differences in cellular morphology, expression
      of other neurotransmitters and afferent and efferent connections. These
      differences among subpopulations of 5-HT neurons may have important implications
      for neural mechanisms underlying 5-HT modulation of sleep and waking. The DRN
      contains 5-HT and non-5-HT neurons. The latter express a variety of substances
      including dopamine, gamma-aminobutyric acid (GABA) and glutamate. In addition,
      nitric oxide and a number of neuropeptides have been characterized in the DRN.
      Available evidence tends to indicate that non-5-HT cells contribute to the
      regulation of the activity of 5-HT neurons during the sleep-wake cycle through
      local circuits and/or their mediation of the effects of afferent inputs. Mutant
      mice that do not express 5-HT(1A) or 5-HT(1B) receptor exhibit greater amounts of
      REMS than their wild-type couterparts. 5-HT(2A) and 5-HT(2C) receptor knockout
      mice show a significant increase of W and a reduction of slow wave sleep that is
      related, at least in part, to the increased release of norepinephrine and
      dopamine. A normal circadian sleep pattern is observed in 5-HT(7) receptor
      knockout mice; however, the mutants spend less time in REMS. Local microinjection
      of 5-HT(1B), 5-HT(2A/2C), 5-HT(3) and 5-HT(7) receptor agonists into the DRN
      selectively suppresses REMS in the rat. In contrast, microinjection of 5-HT(1A)
      receptor agonists promotes REMS. Similarly, local administration of the melanin
      concentrating hormone or the GABA(A) receptor agonist muscimol produces an
      increase of REMS in the rat. Presently, there are no data on the effect of local
      infusion into the DRN of noradrenergic, dopaminergic, histaminergic, orexinergic
      and cholinergic agonists on sleep variables in laboratory animals.

PMID- 20153671
TI  - Improving the sensitivity of Salmonella testing in horses: how good is good
      enough?

PMID- 20153672
TI  - Two unusual clinical and radiological presentations of biotinidase deficiency.
AB  - Biotinidase deficiency is due to a defect in recycling of biotin and is a
      treatable autosomal recessive inherited disorder. We describe two cases with
      unusual presenting symptoms and rarely described MRI findings. We propose that
      the diagnosis of biotinidase deficiency should be considered when there are
      symmetrical MRI changes in the medial thalamus, dorsal brainstem, medulla and
      spinal cord as in our two cases. As long as there isn't newborn screening for
      biotinidase deficiency in the UK; increased awareness of this disorder and
      recognition of biotinidase deficiency as a cause of bilateral symmetrical MRI
      patterns similar to our patients, would facilitate early diagnosis and prevent
      many of the devastating neurological sequelae associated with missing the
      condition.

PMID- 20153673
TI  - Maternally inherited hearing loss is associated with the novel mitochondrial tRNA
      Ser(UCN) 7505T>C mutation in a Han Chinese family.
AB  - Mutations in mitochondrial DNA (mtDNA) have been found to be one of the most
      important causes of sensorineural hearing loss. We report here a clinical,
      genetic, molecular and biochemical characterization of a Han Chinese pedigree
      with maternally transmitted nonsyndromic hearing impairment. Seven of nine
      matrilineal relatives exhibited a variable severity and age-at-onset (8 years
      old) of hearing loss. Mutational analysis of mtDNA identified the novel
      homoplasmic tRNA(Ser(UCN)) 7505T>C mutation and other 37 variants belonging to
      haplogroup F1. The 7505T>C mutation, which is absent in 449 Chinese controls, is
      located at a highly conserved base-pairing (10A-20U) of tRNA(Ser(UCN)). The
      abolishment of 10A-20U base-pairing likely alters the tRNA(Ser(UCN)) metabolism.
      Functional significant of this mutation was supported by approximately 65%
      reductions in the level of tRNA(Ser(UCN)) observed in the lymphoblastoid cell
      lines carrying the 7505T>C mutation, compared with the wild-type cell lines. This
      reduced tRNA level is below the proposed threshold to support a normal
      respiration in lymphoblastoid cells. Furthermore, the highly conserved tRNA(Ala)
      5587T>C and Cytb C93Y variants may have a modifying role of deafness expression
      associated with the 7505T>C mutation. However, genotyping analysis of nuclear
      modifier gene TRMU and the prominent deafness-cause gene GJB2 failed to detect
      any mutations in the member of this family. These data strongly indicate that the
      novel tRNA(Ser(UCN)) 7505T>C mutation is involved in maternally transmitted
      hearing loss. However, other genetic, epigenetic or environmental factors may
      contribute to the phenotypic variability of this family. Our findings will be
      helpful for counseling families of maternally inherited hearing loss.

PMID- 20153674
TI  - [Adverse unidentified transfusion reactions in five French regions: analysis,
      results, propositions].
AB  - OBJECTIVE: Adverse transfusion effects with "unidentified diagnosis" are yearly
      notified on the French national database "e-FIT" in various numbers and with high
      interregional discrepancies. The aim of this work was to analyse them in order do
      reach a better understanding of these notifications. RESULTS: On a total of 2499
      "Fiches d'Effets Indesirables Receveurs" (FEIR) registered in 2006 in five French
      regions, 416 with "unidentified diagnosis" were analysed. Fifty-seven percent of
      them were kept classified in "unidentified diagnosis". Forty-three per cent of
      FEIR were reclassified, some in already proposed diagnostic categories (100 EIR),
      some in new proposed diagnostic categories (80 EIR) as: pathological context of
      the patient, pains linked to transfusion, hypotension. CONCLUSION: The study
      confirms the necessity to re-examine the French notification system. It
      underlines the insufficiency of clinical and biological investigations, which
      could allow to reach accurate diagnosis. It gives prominence the necessity of
      taking into account the patient's pathology and targets at least two diagnoses of
      transfusion adverse effects which are not yet proposed on the FEIR model. This
      work brings an overture about evolution of the French haemovigilance database
      which will involve further developments.

PMID- 20153675
TI  - Education on sensor-augmented pump use improves glucose control in type 1
      diabetic patients.

PMID- 20153676
TI  - Total adiponectin does not predict cardiovascular events in middle-aged men in a
      prospective, long-term follow-up study.
AB  - AIM: Plasma total adiponectin is a marker of insulin resistance, but its role in
      predicting cardiovascular events is unclear. We aimed to investigate the role of
      adiponectin as a predictor of cardiovascular risk in middle-aged men, and to
      describe the association between adiponectin and glucose metabolism. METHODS: In
      this population-based prospective study of middle-aged men (n=3885), total
      adiponectin was analyzed. All individuals had undergone an oral glucose tolerance
      test (OGTTs), and the mean follow-up duration was 27 years. Regression analyses
      were carried out for indices of glucose metabolism in relation to quintiles (Q1
      Q5) of total adiponectin levels. After stratification for smoking or not, the
      association between total adiponectin and the first incidence of fatal or non
      fatal cardiovascular disease (CVD) was analyzed, using Cox's proportional-hazards
      regression model. RESULTS: In a separate multiple-regression analysis and after
      adjusting for possible confounders, the relationship between adiponectin levels
      and markers of glucose metabolism were found to be significant (P<0.05). However,
      adiponectin did not independently predict the risk of stroke, coronary events, or
      a combination of these two outcomes. CONCLUSION: Levels of total plasma
      adiponectin are not useful for predicting long-term cardiovascular events in
      middle-aged men, but are strongly associated with glucose metabolism and markers
      of insulin resistance.

PMID- 20153677
TI  - New tools for diagnosing spondyloarthropathy.
AB  - Ankylosing spondylitis (AS) in its established and early forms accounts for more
      than 5% of all cases of chronic low back pain. Attention has focused recently on
      decreasing the time from symptom onset to the diagnosis of AS, which currently
      ranges from five to 10 years. An earlier diagnosis would lead to improved
      management, in particular thanks to the recent introduction and continuing
      development of biotherapies, such as TNFalpha antagonists, and new imaging
      techniques, including Doppler ultrasonography and magnetic resonance imaging have
      proved capable of detecting early signs of AS. Biotherapies not only improve the
      symptoms, but may also slow or halt the progression of the inflammatory lesions
      before the development of radiographic changes. Current criteria for AS (New
      York, Amor, and ESSG) are classification criteria that provide useful diagnostic
      orientation in clinical practice but have inadequate sensitivity for the
      diagnosis of recent-onset AS. Several groups have been working on means of
      improving the early diagnosis of AS. An algorithm for the early diagnosis of
      axial AS developed by Rudwaleit et al. needs to be confirmed by prospective
      studies. The Assessment of SpondyloArthritis international Society (ASAS) has
      just issued new diagnostic criteria for AS that performed well in a large cohort
      of patients with recent-onset low back pain.

PMID- 20153678
TI  - Thoracic spinal cord compression by a tophus.
AB  - We report a case of thoracic (T10) spinal cord compression by a tophus in a
      patient with known chronic gout. Spastic paraplegia developed gradually over 6
      months in this 43-year-old man with hypertension, alcohol abuse, and chronic
      gouty arthritis with tophi. Magnetic resonance imaging and computed tomography
      visualized an intradural nodule measuring 1.5cm in diameter at the level of T10,
      as well as geodes in the left T10 lamina and left T9-T10 articular processes. The
      nodule was removed surgically and shown by histological examination to be a
      tophus. The neurological impairments resolved rapidly and completely. We found
      about 60 similar cases in the literature. Spinal cord compression in a patient
      with chronic gout can be caused by a tophus.

PMID- 20153679
TI  - [Radiation-induced breast angiosarcoma following breast-conserving therapy.
      Report of two cases].
AB  - Breast angiosarcoma is a rare but serious complication of radiotherapy. We report
      two cases of radiation-induced breast angiosarcoma in two patients having
      benefited from breast conserving surgery with radiation. We shall put emphasis on
      the etiopathogeny of these tumours and their clinical and therapeutic aspects.

PMID- 20153680
TI  - [Is over increase in pelvic ultrasound and MRI justified?].

PMID- 20153681
TI  - [Smoking during pregnancy and smoking clinics].
AB  - OBJECTIVES: France has the highest rate in Europe for smoking during pregnancy,
      the first cause of preterm birth. PATIENTS AND METHODS: We aimed to study the
      accessibility of smoking clinics for pregnant women in Picardy. A woman simulated
      by phone a request for a visit. RESULTS: Smoking cessation visits are poorly
      publicized. The mean delay for a visit is nine days (range: 2-42). Only eight
      centers out of 21 could reduce the delay when it was stressed that the request
      was for a pregnant woman, reducing the delay to seven days (range: 1-16). None of
      the centres has checked for this condition. DISCUSSION AND CONCLUSION: Smoking is
      a major burden. Inconsistencies in the French healthcare system are reviewed.
      Professionals' involvement in smoking cessation programs must be improved,
      however consistency in the support from health care authorities is needed.

PMID- 20153682
TI  - [Modalities for the functionning of a Care Center for women at high risk for
      breast and ovarian cancers: The French experience of Tenon Hospital].
AB  - High risk may be defined as either an absolute risk greater than 20 % or a
      relative risk greater than 4. Concerning breast and ovarian cancer, high risk
      patients include carriers of a constitutive deleterious mutation of BRCA1 or
      BRCA2 genes, patients with a significant family history of breast or ovarian
      cancer, and patients who have been diagnosed a benign breast lesion with a high
      risk of degeneration, i.e. atypical hyperplasia. Following up such patients
      relies on specific strategies. A center including a large panel of physicians
      involved in the various modalities for patients' management (geneticians,
      radiologists, gynecologists, plastic surgeons, pathologists, endocrinologists,
      psychologists, medical oncologists) has been created at Tenon Hospital with this
      purpose. The collaboration of these different specialists with the referent
      physician of the patient allows for the definition and the implementation of a
      patient-centered follow-up continuously updated to take into account the
      different periods of a woman's life, according to best practices recommendations
      and the evolving state-of-the art.

PMID- 20153684
TI  - Tear osmolarity measurement using the TearLab Osmolarity System in the assessment
      of dry eye treatment effectiveness.
AB  - PURPOSE: To evaluate the efficacy of three commercially available lubricant eye
      drops for the treatment of mild, dry, irritated eyes. METHODS: Randomized,
      investigator-masked evaluation of 60 patients in which 20 patients used
      carboxymethylcellulose sodium (CMC), 0.5% (Cellufresh), Allergan Inc., Irvine,
      CA) (group 1); 20 patients used a drop containing polyethylene glycol 400, 2.5%
      and sodium hyaluronate (Blink Intensive Tears, Abbott Medical Optics Inc., Santa
      Ana, CA) (group 2); and 20 patients used HP Guar 0.18% (Systane, Alcon
      Laboratories Inc., Ft. Worth, TX) (group 3). Study visits were at baseline and 1
      month. Tests performed at both visits included Schirmer, tear-film break-up time
      (TBUT), visual acuity, fluorescein staining, tear osmolarity and wavefront
      aberrometry. Osmolarity testing was performed prior to instillation of the
      lubricant eye drops and then a final time 5min after instillation of the drop at
      both day 1 and day 30. Tear osmolarity was performed only in the right eye and
      only one time before and after instillation of lubricant eye drops. RESULTS: At
      day 1 the mean reduction in osmolarity 5min after instillation of the lubricant
      eye drop was, -5.0+/-1.9 in group 1, -9.0+/-4.2 in group 2 and -5.0+/-2.2 in
      group 3. At day 30 the mean reduction in osmolarity 5min after instillation of
      the lubricant eye drop was, -5.6+/-2.3mOsm/L in group 1; -9.9+/-2.8mOsm/L in
      group 2 and -4.5+/-1.8mOsm/L in group 3. The differences were statistically
      significant between groups 1 and 2, and 2 and 3. There was a reduction of
      osmolarity from day 1 to day 30 but the differences were not statistically
      significant. We feel that after a 30-day treatment with the lubricant eye drops,
      the lower osmolarity values could indicate that the tear film is progressing
      towards a more normal osmolarity value. A future study could examine the tear
      osmolarity value after 60 or 90 days of usage. LogMAR best-corrected visual
      acuity (BCVA) results showed an improvement in group 2 compared with baseline
      with no change in BCVA in groups 1 and 3. There was no statistically significant
      change from day 1 to 1 month in TBUT, while the Schirmer test showed an
      improvement in all groups at 1 month. CONCLUSIONS: Assessment of tear osmolarity
      provides the most objective, measurable test for determining improvement in dry
      eye patients. The instillation of any artificial tear or lubricant eye drop
      should decrease the tear-film osmolarity. The results found that polyethylene
      glycol 400, 0.25% and sodium hyaluronate (Blink Intensive Tears) significantly
      improved tear osmolarity compared with carboxymethylcellulose sodium (CMC), 0.5%
      (Cellufresh) and HP Guar 0.18% (Systane after instillation.

PMID- 20153683
TI  - Statistically optimal perception and learning: from behavior to neural
      representations.
AB  - Human perception has recently been characterized as statistical inference based
      on noisy and ambiguous sensory inputs. Moreover, suitable neural representations
      of uncertainty have been identified that could underlie such probabilistic
      computations. In this review, we argue that learning an internal model of the
      sensory environment is another key aspect of the same statistical inference
      procedure and thus perception and learning need to be treated jointly. We review
      evidence for statistically optimal learning in humans and animals, and re
      evaluate possible neural representations of uncertainty based on their potential
      to support statistically optimal learning. We propose that spontaneous activity
      can have a functional role in such representations leading to a new, sampling
      based, framework of how the cortex represents information and uncertainty.

PMID- 20153685
TI  - The publication echo: effects of retrieving literature in PubMed by year of
      publication.
AB  - OBJECTIVES: In PubMed search forms, the publication date refers to both the date
      of electronic and printed publication. This fact is documented in PubMed, but
      difficult to anticipate by the users and can provoke misinterpretations of search
      results. The Technical Note aims at systematically investing the effect (referred
      to as the publication echo), clarifying onset and extent of the publication echo,
      and comments on its impact. METHODS: Papers with ambiguous publication dates are
      systematically retrieved and a trend analysis with seasonal decomposition on
      monthly publication data is performed. RESULTS: First doubled search results were
      found for 1999, their number since then rapidly increasing. Up to 17.6% of all
      articles of a year are found to be published electronically and in print, which
      can be before or afterwards. Maximum delay between the two dates is three years,
      except for one singular publication, where it is five years. Publication trends
      are exponential and linear when considering echoed and echo-cleaned data,
      respectively. CONCLUSIONS: As a conclusion, we suggest using a query formulation
      that unambiguously retrieves literature from PubMed by the date of publication.

PMID- 20153686
TI  - Effect of movement on SEPs generated by dorsal column nuclei.
AB  - OBJECTIVE: To investigate the effect of the voluntary movement on the amplitude
      of the somatosensory evoked potentials (SEPs) recorded by an epidural electrode
      at level of the dorsal column nuclei (DCN). METHODS: Five patients, suffering
      from chronic pain resistant to pharmacological treatment, underwent an epidural
      electrode implant at high cervical spinal cord level (C2) for neuromodulation.
      After tibial nerve stimulation, SEPs were recorded from the epidural electrode
      contacts, from a Cz lead, and from two electrodes placed over the 12th dorsal
      vertebra and 4th lumbar vertebra, respectively. SEPs were recorded at rest and
      during a voluntary flexo-extension movement of the stimulated foot. Beyond the
      low-frequency SEPs, also the high-frequency oscillations (HFOs), obtained by
      filtering the recorded traces by means of a 1000-2000 Hz bandpass offline, were
      analysed. RESULTS: The epidural electrode contacts recorded a triphasic potential
      (P1-N1-P2), whose negative peak showed a latency similar to that of the P30 far
      field response obtained from the scalp. The epidural potential amplitude was
      significantly decreased by the voluntary movement, as compared to the rest
      (p<0.01). A main HFO peak, identifiable at around 1200 Hz, was significantly
      lower in amplitude during movement than at rest (p=0.008). CONCLUSIONS: Our
      findings suggest that the epidural C2 triphasic wave is a potential arising from
      DCN. The low-frequency epidural SEP component is subtended by a 1200 Hz HFO,
      probably generated by post-synaptic events. SIGNIFICANCE: The amplitude reduction
      of the DCN response during movement is possibly due to decreased excitability of
      the DCN neurons receiving the somatosensory ascending input.

PMID- 20153687
TI  - Complex regional pain syndrome as a complication to electroneuronography.

PMID- 20153688
TI  - Light sleep and sleep time misperception - relationship to alpha-delta sleep.
AB  - OBJECTIVE: We investigated the association of alpha-delta sleep (A-DS) with: (1)
      perception of light sleep and (2) discrepancy between subjective and objective
      sleep duration. METHODS: We analyzed data from 5764 individuals who underwent
      polysomnography (PSG) and replied questions about quantity and quality of sleep,
      including sleep depth. The difference between objectively recorded sleep time and
      subjectively estimated sleep time was calculated. Alpha-delta sleep (A-DS) was
      visually scored in a scale from 1 to 4, based on the density and overnight
      duration of alpha activity and confirmed using spectral array of the
      electroencephalographic activity. RESULTS: A-DS scores 1-4 occurred in,
      respectively, 37.9%; 31.3%; 20.5%; and 6.2% of the cases. ANOVA showed
      significant difference of light sleep sensation (p<0.001) and sleep time
      underestimation (p<0.001) among the four A-DS categories. Regression to explain
      both light sleep and sleep time underestimation, controlling for confounders,
      confirmed A-DS as a significant regressor. CONCLUSIONS: This study of a large
      prospective sample provides evidence for the association of alpha-delta sleep
      with subjective sensation of light sleep and with sleep time underestimation.
      SIGNIFICANCE: Alpha-delta sleep may be a marker of the physiological disorder
      underlying light sleep and sleep state misperception.

PMID- 20153689
TI  - EEG features and epilepsy in MECP2-mutated patients with the Zappella variant of
      Rett syndrome.
AB  - OBJECTIVE: To assess the presence/absence of peculiar EEG features and epilepsy
      in MECP2-mutated Rett patients with the Zappella-Rett variant (Z-RTT) also known
      as preserved speech variant. METHODS: Retrospective analysis of 16 (age 19.4+/
      8.4years; range 8-38years) MECP2 mutated Z-RTT cases, including 11 high or
      intermediate performance (HIP), and five low-performance (LP) patients was
      performed. Peculiar EEG features were analyzed as a function of the HIP or LP Z
      RTT categories: (1) centro-temporal spikes, (2) multifocal EEG activity, (3) EEG
      encephalopathy (i.e. multifocal EEG activity associated with the presence of
      background slowing and diffuse slow activity), (4) spindles and K-complex.
      Furthermore, we assessed the occurrence of epilepsy. Correlations between
      electroclinical features and category of Z-RTT genotype (missense or truncation
      mutation) were also tested. RESULTS: The Z-RTT HIP group showed a very abnormal
      EEG (presence of centro-temporal spikes: p=0.004808), although the cases studied
      were not epileptogenic and did not develop encephalopathy. The LP group showed
      multifocal EEG activity (p=0.000229), EEG encephalopathy (p=0.000229) and
      epilepsy (p=0.299451). No significant differences between the prevalence of
      centro-temporal spikes, multifocal EEG activity, EEG encephalopathy, and epilepsy
      between the patients with the truncation or missense mutation were observed.
      CONCLUSIONS: EEG electrophysiological patterns and epileptogenic susceptibility
      differ in Z-RTT according to the level of performance (i.e. HIP or LP).
      SIGNIFICANCE: These results indicate that HIP and LP Z-RTT should be considered
      as distinct entities, not only on a clinical basis, but also as it concerns EEG
      features and epileptogenic susceptibility. These results could offer support in
      the practical management of patients and family counseling.

PMID- 20153690
TI  - Interactions of glutamate and capsaicin-evoked muscle pain on jaw motor functions
      of men.
AB  - OBJECTIVE: The aim of the study was to investigate the interaction between
      glutamate and capsaicin-evoked muscle pain on human jaw motor functions. METHODS:
      Fifteen male volunteers participated. Glutamate or capsaicin or isotonic saline,
      in a paired-sequence order, was injected randomly into the right or left masseter
      muscle. Two injections were given in a double-blinded design 25 min apart in one
      session/week over four weeks: isotonic saline (A1) followed by glutamate (A2),
      capsaicin (B1) followed by glutamate (B2), isotonic saline (C1) followed by
      capsaicin (C2), and glutamate (D1) followed by capsaicin (D2). The resting
      electromyographic (EMG) activity of the right and left masseter muscles, maximum
      voluntary bite force (MVBF), and maximum voluntary jaw opening (MVJO) were
      recorded before and after injection and subsequently at 5-min intervals for 50
      min. The pain intensity was recorded on a 0-10 numerical rating scale during each
      MVBF or MVJO jaw function. RESULTS: Resting EMG activity was significantly
      increased after 5 min of D2 (ANOVA: P=0.028) injection. The percentage change
      (compared with baseline) in EMG activity was significantly different between D2
      (116.1+/-6.1%) and C2 (102.1+/-3.4%) injections (paired t-test: P=0.039). The
      MVBF and MVJO were significantly decreased after injection of glutamate or
      capsaicin, however, there was no significant difference in the relative decrease
      between A2 and B2, or between C2 and D2 at any time point (P>0.152). There was a
      significantly higher peak pain rating after D2 compared to C2 during MVBF or MVJO
      (P<0.022), whereas no significant difference in peak pain ratings was found
      between A2 and B2 (P>0.084). There were significant negative correlations between
      pain ratings and MVBF or MVJO (Pearson correlation: P<0.001). CONCLUSIONS: The
      results indicate that intramuscular administration of glutamate and capsaicin
      induces muscle pain which has the potential to perturb some normal jaw motor
      functions. SIGNIFICANCE: The present findings suggest that peripheral glutamate
      and capsaicin receptor mechanisms interact to affect some jaw motor as well as
      sensory (i.e. pain) functions and provide new insights into the complexity of
      orofacial pain. Management approaches that target the peripheral nervous system
      and receptor mechanisms may prevent such changes in jaw motor function.

PMID- 20153691
TI  - The use of EEG in Alzheimer's disease, with and without scopolamine - a pilot
      study.
AB  - OBJECTIVE: To use multivariate statistical analysis of EEG data in order to
      separate EEGs of patients with Alzheimer's disease (AD) from controls. A group of
      individuals with mild cognitive impairment (MCI) was evaluated using the same
      methodology. Additionally, the effects of scopolamine on this separation are
      studied. METHODS: Statistical pattern recognition (SPR) is used in conjunction
      with information extracted from EEGs before and after administration of
      scopolamine. RESULTS: There was complete separation of the AD group and controls
      before administration of scopolamine. The separation increased after scopolamine
      had been given. Of the 10 MCI individuals, five seemed to belong to the AD group.
      Three of those progressed to AD within 1 year and one after 3 years. CONCLUSIONS:
      Using SPR on EEG recordings it is possible to separate AD from controls. This
      separation can be increased by the use of scopolamine but the medication is not a
      prerequisite for classification. The results indicate that SPR is useful for
      predicting progress of MCI to AD. SIGNIFICANCE: EEG registration is a simple and
      noninvasive method. If these results are confirmed in other studies, this method
      could be more widely applied than the highly specialized methods used today in
      detection of early AD.

PMID- 20153692
TI  - Magnetic and electric stimulation to elicit the masseteric exteroceptive
      suppression period.
AB  - OBJECTIVES: The present study compared the perception of electric and magnetic
      stimuli for reflex appearance threshold (RT) and reflex saturation threshold (RS)
      of the exteroceptive suppression reflex (ES) in the masseter muscle. METHODS:
      Twelve healthy males and 12 females (age: 24.2+/-3.2 years) participated. The
      surface EMG was recorded from the left masseter muscle. The stimulus intensities
      were set as multiple values of the sensory threshold (ST), and were applied to
      the skin above the left mental nerve. Subjects reported the perceived intensity
      of the stimulus on a numeric rating scale (NRS) at RT and RS for the early and
      late ES (ES1 and ES2, respectively). RESULTS: ES2 had a lower RT and RS compared
      to ES1 in electric and magnetic stimulation. Significantly lower NRS values at RT
      and RS were found with painless magnetic stimulation compared to electric
      stimulation (p<0.01). CONCLUSIONS: In contrast to electrical stimulation, both
      ES1 and ES2 appeared and saturated with painless magnetic stimuli. SIGNIFICANCE:
      The present results indicate that both ES1 and ES2 have a non-nociceptive origin.
      Painless magnetic stimuli will be an advantage in ES reflex examinations for
      various orofacial pain conditions.

PMID- 20153693
TI  - An evaluation of the use of the LSU rRNA D1-D5 domain for DNA-based taxonomy of
      eukaryotic protists.
AB  - Diagnostic signature DNA sequences are important tools for the identification of
      species. There is an active debate in the literature on the choice of the best
      markers applicable for a broad range of organisms. Protists have seldom been
      included in these evaluations. Mitochondrial gene sequences are inappropriate for
      protists since several groups do not possess mitochondria. Here we studied the
      application of the large subunit (LSU) rRNA gene fragments (D1-D5) regarding
      their usefulness to discriminate between a wide range of heterotrophic
      nanoflagellates. Phylogenetic analyses based on the LSU rRNA fragments showed
      similar results compared to phylogenetic trees based on the small subunit (SSU)
      rRNA. The data set indicates the power of the use of the D1-D5 region as a marker
      for a DNA-based taxonomy. Our results, together with the available sequences in
      Genbank, form a comprehensive database for unicellular eukaryotes, especially
      heterotrophic flagellates. It is now possible to assign new sequences to the
      different groups of heterotrophic flagellates which we have tested for different
      closely related Cercomonas and Paracercomonas strains from groundwater.

PMID- 20153694
TI  - Phospholipase PlaB is a new virulence factor of Legionella pneumophila.
AB  - We previously identified Legionella pneumophila PlaB as the major cell-associated
      phospholipase A/lysophospholipase A with contact-dependent hemolytic activity. In
      this study, we further characterized this protein and found it to be involved in
      the virulence of L. pneumophila. PlaB was mainly expressed and active during
      exponential growth. Active PlaB was outer membrane-associated and at least in
      parts surface-exposed. Transport to the outer membrane was not dependent on the
      type I (T1SS), II (T2SS), IVB (T4BSS) or Tat secretion pathways. Furthermore,
      PlaB activity was not dependent on the presence of the macrophage infectivity
      potentiator (Mip) or the major secreted zinc metalloproteinase A (MspA). Despite
      the fact that PlaB is not essential for replication in protozoa or macrophage
      cell lines, we found that plaB mutants were impaired for replication in the lungs
      and dissemination to the spleen in the guinea pig infection model. Histological
      sections monitored less inflammation and destruction of the lung tissue after
      infection with the plaB mutants compared to L. pneumophila wild type. Taken
      together, PlaB is the first phospholipase A/lysophospholipase A with a confirmed
      role in the establishment of Legionnaires' disease.

PMID- 20153695
TI  - Oxidative damage in foundry workers occupationally co-exposed to PAHs and metals.
AB  - Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) has been
      reported in foundries. A higher risk for DNA damage or oxidative damage lesions
      was also found in occupationally PAH-exposed groups. The aim of this study was to
      assess PAH exposure by urinary excretion of 1-hydroxypyrene (1-OHP), a biological
      exposure marker. Furthermore, we aimed to evaluate the oxidative damage of
      foundry workers with different job tasks and the association between 1-OHP, metal
      exposure and oxidative damage in foundry workers exposed to pervasive
      carcinogens. A higher concentration of 1-OHP was found in the exposed group
      (0.322+/-0.289 microg/g creatinine) relative to the control group (0.178+/-0.289
      microg/g creatinine) (p<0.05). Moreover, higher levels of 1-OHP were found in
      workers involved in manufacturing processes (0.346 microg/g creatinine) compared
      to administrative workers (0.018 microg/g creatinine). A positive correlation was
      identified between levels of 1-OHP and 8-hydroxydeoxyguanosine (8-OH-dG), DNA
      strand breakage and malondialdehyde (MDA) in all study subjects. However, when
      foundry workers were considered based on their specific job categories, a similar
      trend for 1-OHP and three oxidative damage markers was only found for DNA strand
      breakage, but not for 8-OH-dG or MDA. Other factors such as furnace equipment,
      PAH types, and job categories may contribute to different PAH emissions. The
      study also suggested that co-exposure to metal and PAHs, and smoking status in
      foundry industries may also cause the oxidative damage in foundry workers.

PMID- 20153696
TI  - Coronary artery anatomy and apical sparing in apical ballooning syndrome:
      implications for diagnosis and aetiology.
AB  - BACKGROUND: Apical ballooning syndrome (ABS) is characterised by transient
      regional systolic dysfunction involving the left ventricular apex and mid
      myocardial segments. The absence of obstructive coronary disease is required in
      some diagnostic criteria. Some investigators have suggested that a long "wrap
      around" left anterior descending (LAD) artery may explain the pattern of regional
      wall motion abnormalities. METHODS AND RESULTS: We reviewed the coronary
      angiograms and ventriculograms findings in a prospective ABS cohort of 46
      patients (mean age 63+/-13, female 96%). Normal smooth coronary arteries were
      observed in 54%, with 30% having minor irregularities. Moderate or severe
      coronary artery lesions were identified in 7 (15%) patients, including 4 with
      moderate LAD disease. The extent of the LAD artery around the left ventricular
      apex to the diaphragmatic surface of the heart was scored. This score was
      compared to 60 consecutive gender-matched control patients without ABS and no
      observed difference between the two groups (p=0.62). 42% had sparing of LV apical
      akinesis which was independent of the LAD extent. CONCLUSION: Moderate or severe
      coronary artery stenosis may co-exist in a small proportion of patients with ABS.
      Exclusion of these patients will underestimate the true incidence of ABS. The
      prevalence of "wrap-around" LAD is similar in ABS and non-ABS patients. Apical
      sparing in ABS is more consistent with aetiological hypotheses implicating LV
      stunning due to acutely elevated LV wall stress, rather than single or multi
      vessel coronary spasm.

PMID- 20153697
TI  - MICA polymorphism: biology and importance in immunity and disease.
AB  - The human major histocompatibility complex class I chain-related gene A (MICA) is
      one of the genes in the HLA class I region of chromosome 6. Unlike HLA classical
      class I gene products, MICA does not present any antigen but acts as a ligand for
      several immune cells including natural killer (NK) cells bearing NKG2D receptors.
      MICA is the member of the non-classical class I family that displays the greatest
      degree of polymorphism. MICA alleles can be divided into two large groups with
      the polymorphisms found in alpha3 domains. This division could be explained by a
      possible polyphyletic origin that is in line with recent findings from
      evolutionary, population and functional studies of this gene. MICA polymorphisms
      are associated with a number of diseases related to NK activity, such as viral
      infection, cancer and allograft rejection or graft-versus-host disease (GVHD).
      The mechanisms underlying these associations include NK cell-mediated
      cytotoxicity and MICA shedding to produce immunosuppressive soluble MICA
      particles. The MICA-induced humoral response has attracted interest recently
      because of its possible role in graft rejection in solid organ transplantation.
      Here, we discuss the genetics and biology of the MICA gene and its products, and
      their importance in disease.

PMID- 20153698
TI  - Oxidative stress status and lipid profiles of diabetic pregnant rats exposed to
      cigarette smoke.
AB  - This study aimed to evaluate the oxidative stress status and the concentrations
      of triglycerides, cholesterol and total proteins of pregnant rats exposed to the
      association of diabetes and cigarette smoke. Female Wistar rats were randomly
      distributed in four experimental groups, according to presence or not of diabetes
      and the exposure or not to cigarette smoke. Diabetes was induced by
      streptozotocin (40 mg/kg i.v.) and exposure to cigarette smoke was for 30 min,
      twice a day, for 2 months. At day 21 of pregnancy, blood was collected for total
      protein, triglyceride, cholesterol and oxidative stress determinations. Data were
      analysed by ANOVA followed by Student-Newman-Keuls test (P<0.05). The association
      of diabetes and exposure to cigarette smoke was related to the incidence of
      hypertriglyceridaemia, and this result was due to the severe diabetes and not to
      exposure to smoke. There was no alteration to protein metabolism in pregnant
      rats. Diabetes and cigarette smoke exposure led to the activation of the
      antioxidant system in an attempt to detoxify the organism in face of high lipid
      peroxidation, which can be characterized by the determination of reactive
      substances to thiobarbituric acid.

PMID- 20153699
TI  - Successful surgical correction of an extreme form of ectopic penis.
AB  - Reported here is the successful multi-staged repair of a rare case of complete
      penoscrotal transposition with ectopic penis. The need to evaluate for associated
      anomalies is discussed.

PMID- 20153700
TI  - Prospective randomized trial comparing dissection with Plastibell(r)
      circumcision.
AB  - OBJECTIVE: To compare and evaluate dissection and Plastibell((r)) circumcision
      techniques for the treatment of phimosis. METHODS: In 2006-2007, 125 children
      were submitted to circumcision by the same surgeon. The children were randomly
      divided into two groups (PD: Plastibell((r)) and DC: dissection). In both groups
      the surgery was performed under general anesthesia and dorsal penile block. The
      dissection circumcision used the double circular incision technique. Follow-up
      was done on days 15, 45 and 90 after surgery. RESULTS: Sixty-eight patients were
      included in DC and 57 in PD. The mean age at surgery was 71.76 +/- 31.56 months
      for DC and 70.95 +/- 31.73 months for PD. There was no difference in Kayaba's
      classification for phimosis or indication for surgery between the groups.
      Surgical time for DC was 14.64 +/- 1.93 min and for PD 3.29 +/- 1.48 min (P <
      0.001). The incidence of immediate complications was similar, but late
      complications, especially adhesions, were greater in DC (P < 0.01). The use of
      pain medication (paracetamol) was similar during the first 2 days after surgery,
      but was greater in PD from the 3rd day after surgery (P < 0.05). CONCLUSIONS:
      Plastibell((r)) circumcision has a shorter surgical duration with fewer late
      complications, but requires more analgesic medication after the 3rd day post
      surgery.

PMID- 20153701
TI  - Knowledge, attitudes and practices with respect to epilepsy among student nurses
      and laboratory assistants in the South West Region of Cameroon.
AB  - OBJECTIVE: This study was designed as part of a series of studies mandated by the
      Cameroon Ministry of Public Health (National Epilepsy Control Program) to obtain
      new data for improvement of the epilepsy teaching program in schools training
      health personnel in the South West Region of Cameroon. METHOD: A 12-item
      semistructured questionnaire was self-administered to 340 student nurses and
      laboratory assistants in five training schools for health personnel in the South
      West Region of Cameroon. RESULTS: All of them had heard about epilepsy, 86.5%
      knew someone with epilepsy, 88.5% had witnessed a seizure, but only 48.8% had
      read about epilepsy. About 33% and 52% would, respectively, object to their
      children associating with and marrying people with epilepsy (PWE). About 15.3%
      believed that epilepsy is a form of insanity, 10% thought epilepsy is contagious,
      67.4% (P<0.001) would recommend medical treatment for epilepsy, 22% would offer
      prayers only, and 6% would recommend traditional medicine. Independent predictors
      of attitudes were: acquaintance with someone with epilepsy, knowledge of the
      cause of epilepsy, the belief that epilepsy is contagious or is a form of
      insanity, being male, and being in the first year of studies. CONCLUSION: The
      knowledge level in this student sample is high, but the relatively low proportion
      of respondents who have read about epilepsy suggests that the observed high level
      of awareness of epilepsy may be from knowledge gained in the community; thus,
      there exist knowledge gaps. Therefore, a teaching course on epilepsy needs to be
      introduced into the curriculum of these training schools as early as the first
      year of studies. The course content must take into account the belief and value
      systems of the community and address misconceptions about epilepsy.

PMID- 20153702
TI  - Platelet proinflammatory activity in clinically stable patients with CF starts in
      early childhood.
AB  - BACKGROUND: Early onset chronic inflammation is present in CF. Platelets may
      contribute to inflammation by cytokine release and interaction with leukocytes.
      METHODS: Parameters of platelet proinflammatory function (soluble CD62P, soluble
      CD40L, the percentage of platelet-leukocyte aggregates, platelet CD62P) and
      platelet procoagulatory function (PAC-1-binding to activated integrin
      alpha(IIb)beta(3) and expression of integrin alpha(IIb)beta(3)=CD41a) were
      measured in patients and controls. RESULTS: Levels of sCD62P, sCD40L were
      increased in CF irrespective of age and activity of inflammation. The number of
      platelet-leukocyte aggregates was elevated in older CF patients. PAC-1-binding to
      platelets decreased with growing activity of inflammation. Exocytosis of CD41a
      upon platelet activation was reduced. CONCLUSION: In CF, platelet proinflammatory
      activity is increased at very young age already and might promote inflammation
      and tissue damage. On the other hand, platelets seem to downregulate the
      activation of their most important integrin (alpha(IIb)beta(3)) for clot
      formation.

PMID- 20153703
TI  - Determination of melamine and cyanuric acid in human urine by a liquid
      chromatography tandem mass spectrometry.
AB  - Melamine was found to be the etiological factor for the urinary stones epidemic
      in infants and young children in China in 2008. Urine level of melamine and its
      analog cyanuric acid may be useful markers for the evaluation of toxic effects.
      Liquid chromatography tandem mass spectrometry methods for the individual
      determination of melamine and cyanuric acid in human urine are described. Using
      isotope labeled internal standards during liquid-liquid extraction, the method
      was fully validated by verifying specificity, linearity, LLOQ, intra- and inter
      assay precision and accuracy, matrix effect, recovery and stability. Calibration
      curves with good linearity (r=0.9999) over the concentration range from 10 to
      5000 ng/ml, intra-assay precision <10% and inter-assay precision <15%, accuracy
      between 93.0 and 111.6% were obtained with multiple reaction monitoring mode for
      melamine and cyanuric acid in human urine. The methods were successfully applied
      to the analysis of urine samples collected from 86 infants and 110 adults.

PMID- 20153704
TI  - Replacement of acetonitrile by ethanol as solvent in reversed phase
      chromatography of biomolecules.
AB  - Acetonitrile, which is a by-product of acrylonitrile synthesis, is the commonly
      used solvent in ion-pair reversed phase chromatography. In consequence of the
      decreasing demand for acrylonitrile due to the financial crisis, a worldwide
      shortage of acetonitrile is observed. Therefore, the aim of this study was to
      establish ion-pair reversed phase chromatographic assays using alternative
      eluents for acetonitrile and to decrease costs incurred hereby. We compared the
      performance of ion-pair reversed phase chromatography using acetonitrile with the
      alternative eluents methanol, ethanol and n-propanol, using monolithic reversed
      phase C5 as well as C18 chromatography columns. We used triethylammonium acetate
      (TEAA) and tetrabutylammonium sulfate (TBA) as representative cationic ion-pair
      reagents and trifluoroacetic acid (TFA) as representative anionic ion-pair
      reagent. For covering a large field of applications, we fractionated
      representative low, middle and high-molecular weight biomolecules, in particular
      dinucleoside polyphosphates, peptides, proteins and tryptic digested human serum
      albumin. Whereas the chromatographic characteristics of both methanol and n
      propanol were partly insufficient, ethanol was characterised equally or partly
      even better in the matter of elution strength and separation quality compared to
      the eluent water-acetonitrile. In conclusion, ethanol is an appropriate
      alternative for acetonitrile in ion-pair reversed phase chromatography of
      biomolecules.

PMID- 20153705
TI  - Development and validation of a dried blood spot-LC-APCI-MS assay for estimation
      of canrenone in paediatric samples.
AB  - A selective and sensitive liquid chromatography (LC)-atmospheric pressure
      chemical ionisation (APCI)-mass spectroscopic (MS) assay of canrenone has been
      developed and validated employing Dried Blood Spots (DBS) as the sample
      collection medium. DBS samples were prepared by applying 30 microl of spiked
      whole blood onto Guthrie cards. A 6mm disc was punched from the each DBS and
      extracted with 2 ml of methanolic solution of 17alpha-methyltestosterone
      (Internal Standard). The methanolic extract was evaporated to dryness and
      reconstituted in acetonitrile:water (1:9, v/v). The reconstituted solution was
      further subjected to solid phase extraction using HLB cartridges. Chromatographic
      separation was achieved using Waters Sunfire C18 reversed-phase column using
      isocratic elution, followed by a high organic wash to clear late eluting/highly
      retained components. The mobile phase consisted of methanol:water (60:40, v/v)
      pumped at a flow rate of 0.3 ml/min. LC-APCI-MS detection was performed in the
      selected-ion monitoring (SIM) mode using target ions at m/z 341.1 and 303.3 for
      canrenone and internal standard respectively. The selectivity of the method was
      established by analysing DBS samples from 6 different sources (individuals). The
      calibration curve for canrenone was found to be linear over 25-1000 ng/ml
      (r>0.994). Accuracy (% RE) and precision (% CV) values for within and between day
      were <20% at the lower limit of quantification (LLQC) and <15% at all other
      concentrations tested. The LLOQ of the method was validated at 25 ng/ml. Clinical
      validation of the method was achieved by employing the validated method for
      analysis of 160 DBS samples from 37 neonatal and paediatric patients.

PMID- 20153706
TI  - [Prevalence of metabolic syndrome and consistency in its diagnosis in type 2
      diabetic patients in Spain].
AB  - OBJECTIVE: To determine the prevalence of metabolic syndrome, the degree of
      consistency among World Health Organization (WHO), The Third Report National
      Cholesterol Education Program (NCEP-ATP III) and the International Diabetes
      Federation (IDF) diagnostic criteria and the relationship with cardiovascular
      risk in a Spanish population of patients with type 2 diabetes. MATERIAL AND
      METHODS: This descriptive, epidemiologic, multicenter and cross-sectional study
      included 1259 patients with type 2 diabetes. The primary variable was diagnosis
      of metabolic syndrome according to WHO, NCEP-ATP III and IDF criteria. RESULTS:
      The prevalence of metabolic syndrome was 71.5% (WHO), 78.2% (NCEP-ATP III), and
      89.5% (IDF). The prevalence of metabolic syndrome was higher in sedentary
      diabetic patients (WHO=79.3%, NCEP-ATP III=86.2%, and IDF=93.9) than in those who
      exercised moderately (WHO=61.4%, NCEP-ATP III=73.2%, and IDF=85.5%, [p<0.001]).
      The percentage of patients with metabolic syndrome and moderate/high
      cardiovascular risk was 38.9% (WHO), 33.6% (NCEP-ATP III), and 30.1%, (IDF).
      Consistency among WHO, NCEP-ATP III and IDF criteria was low. Only comparison of
      WHO vs NCEP-ATP III criteria was acceptable (k=0.52 [0.46-0.58]). CONCLUSIONS:
      The prevalence of metabolic syndrome in patients with type 2 diabetes in Spain is
      high, even when the low consistency among WHO, NCEP-ATP III and IDF criteria is
      considered. A standard definition of metabolic syndrome, according to routine
      clinical practice, is needed. Cardiovascular risk is greater when OMS and NCEP
      ATP III criteria are used for the diagnosis of metabolic syndrome compared with
      IDF criteria.

PMID- 20153707
TI  - [Consensus conference on acute bronchiolitis (II): epidemiology of acute
      bronchiolitis. Review of the scientific evidence].
AB  - A review of the evidence on epidemiology, risk factors, etiology and clinical
      etiological profile of acute bronchiolitis is presented. The frequency estimates
      are very heterogeneous; in the population under two years the frequency of
      admission for bronchiolitis is between 1 and 3.5%, primary care consultations
      between 4 and 20% and emergency visits between 1 and 2%. The frequency of
      admissions for respiratory infection by respiratory syncytial virus in the risk
      population is: in premature infants < or =32 weeks of gestation between 4.4 and
      18%, in patients with bronchopulmonary dysplasia between 7.3 and 42%, and in
      infants with congenital heart disease between 1.6 and 9.8%. The main risk factors
      are: prematurity, chronic lung disease or bronchopulmonary dysplasia, congenital
      heart disease and age less than 3-6 months at onset of the epidemic. Other
      factors are: older siblings or day care attendance, male gender, exposure to
      smoking, breastfeeding for less than 1-2 months and variables associated with
      lower socioeconomic status. Respiratory syncytial virus is the dominant
      etiological agent, constituting just over half the cases (median 56%; interval
      27% to 73%). Other viruses implicated, in descending order of frequency, are
      rhinovirus, adenovirus, metapneumovirus, influenza viruses, parainfluenza,
      enterovirus and bocavirus. In studies with genomic detection techniques, between
      20 and 25% of cases the virus involved is not identified and between 9% and 27%
      of cases have viral co-infection. Although respiratory syncytial virus
      bronchiolitis shows more wheezing and retractions, longer duration of respiratory
      symptoms and oxygen therapy and are associated with lower use of antibiotics.
      This pattern is associated with the younger age of the patients and does not help
      us to predict the etiology. In general, the etiological identification is not
      useful for the management of patients. However, in young infants (<3 months) with
      febrile bronchiolitis in the hospital environment, conservative management may
      help these patients and avoid diagnostic and therapeutic procedures.

PMID- 20153708
TI  - [Consensus conference on acute bronchiolitis (I): methodology and
      recommendations].
AB  - The recommendations of the Consensus Conference "Diagnostic and Therapeutic
      Management of Acute Bronchiolitis" are presented. Evidence on the frequency of
      bronchiolitis in the general population and risk groups, risk factors and markers
      of severe forms, severity scores and the clinical-etiological profile is
      summarized. The commonly used diagnostic tests are ineffective in the management
      of the disease; oxygen saturation measurement is considered necessary only in the
      initial assessment or to monitor changes in patients with respiratory distress.
      Other tests such as chest radiograph, rapid diagnostic tests for respiratory
      virus infection and screening tests for bacterial infection should be used only
      very selectively. There is sufficient evidence on the lack of effectiveness of
      most interventions tested in bronchiolitis. Apart from oxygen therapy, fluid
      therapy, aspiration of secretions and ventilation support, few treatment options
      will be beneficial. Only in moderate-severe bronchiolitis would it be justified
      to test a treatment with inhaled bronchodilators (salbutamol or epinephrine) with
      or without hypertonic saline solution. Heliox and non-invasive ventilation
      techniques could be used in cases with respiratory failure, methylxanthine in
      patients with apnea and surfactant in intubated critically ill patients. No
      treatment has proved effective in preventing persistence or recurrence of post
      bronchiolitis symptoms. As for prevention of bronchiolitis, only palivizumab
      slightly reduces the risk of admissions for lower respiratory infections by
      respiratory syncytial virus, although its high cost justifies its use only in a
      small group of high-risk patients.

PMID- 20153709
TI  - The effects of exercise on body satisfaction and affect.
AB  - This research used ecological momentary assessment to examine the effects of
      exercise on state body dissatisfaction and affect in 33 undergraduate females
      with high trait body dissatisfaction and 28 with low trait body dissatisfaction
      who exercised at least three times weekly. Trait body dissatisfaction was
      investigated as a moderator of the effects of exercise as well as different
      motivations for exercise. Results indicated all participants experienced lower
      state body dissatisfaction and negative affect and greater positive affect post
      exercise. Trait body dissatisfaction moderated the association between
      motivations and exercise effects. Appearance and weight motivations were related
      to higher state body dissatisfaction for all individuals. Fitness and health
      motivations were related to higher state body dissatisfaction for high trait body
      dissatisfied individuals and lower state body dissatisfaction for low trait body
      dissatisfied individuals. Thus, although exercise has positive effects on body
      dissatisfaction and affect for high frequency exercisers, their exercise
      motivations impact these effects.

PMID- 20153710
TI  - A peculiar case of spontaneous bilateral mammary implant capsule detachment.

PMID- 20153711
TI  - Quantitation of ceramides in nude mouse skin by normal-phase liquid
      chromatography and atmospheric pressure chemical ionization mass spectrometry.
AB  - A sensitive and accurate normal-phase liquid chromatography and atmospheric
      pressure chemical ionization mass spectrometry (LC-APCI-MS) method for
      determining the standard ceramide [NS] (Cer[NS]) was developed and validated so
      as to improve the traditional thin-layer chromatography (TLC) technique and LC
      electrospray ionization (ESI)-MS method to profile and quantify ceramides in nude
      mouse skin. Normal-phase LC-APCI-MS was optimized to separate the nine classes of
      ceramides presented in the stratum corneum (SC) of nude mouse skin. A normal
      phase silica column eluted with the gradient system from heptane:acetone/butanol
      (90:10, v/v) of 75:25 to 100% acetone/butanol (90:10, v/v) (with each solvent
      containing 0.1% [v/v] triethylamine and 0.1% [v/v] formic acid) at a flow rate of
      0.8 ml/min was found to be optimal for analyzing standard Cer[NS]. The analysis
      of Cer[NS] was validated and employed as the standard for constructing a
      calibration curve to quantitate all classes of ceramides. This method was applied
      to profile the classes and contents of ceramides in the SC of nude mouse skin and
      proved to be workable. It was concluded that this improved method can be used to
      directly detect and quantify all classes of ceramides in the SC of nude mouse
      skin and that it is more convenient and labor-saving than the traditional TLC
      method.

PMID- 20153712
TI  - PKA-mediated effect of MAS receptor in counteracting angiotensin II-stimulated
      renal Na+-ATPase.
AB  - We showed previously that angiotensin-(1-7) [Ang-(1-7)] reversed stimulation of
      proximal tubule Na+-ATPase promoted by angiotensin II (Ang II) through a D-ala(7)
      Ang-(1-7) (A779)-sensitive receptor. Here we investigated the signaling pathway
      coupled to this receptor. According to our data, Ang-(1-7) produces a MAS
      mediated reversal of Ang II-stimulated Na+-ATPase by a Gs/PKA pathway because:
      (1) the Ang-(1-7) effect is reversed by GDPbetaS, an inhibitor of trimeric G
      protein and Gs polyclonal antibody. Cholera toxin, an activator of Gs protein,
      mimicked it; (2) in the presence of Ang II, Ang-(1-7) increased the PKA activity
      10-fold; (3) the peptide inhibitor of PKA blocked the Ang-(1-7) effect on Ang II
      stimulated Na+-ATPase; (4) Ang-(1-7) reverses the Ang II-stimulated PKC activity;
      (5) cAMP mimicked the Ang-(1-7) effect on the Ang II-stimulated Na+-ATPase. Our
      results provide new understanding about the signaling mechanisms coupled to MAS
      receptor-mediated renal Ang-(1-7) effects.

PMID- 20153713
TI  - Inhibition of human arginase I by substrate and product analogues.
AB  - Human arginase I is a binuclear manganese metalloenzyme that catalyzes the
      hydrolysis of L-arginine to generate L-ornithine and urea. We demonstrate that N
      hydroxy-L-arginine (NOHA) binds to this enzyme with K(d)=3.6 microM, and nor-N
      hydroxy-L-arginine (nor-NOHA) binds with K(d)=517 nM (surface plasmon resonance)
      or K(d) approximately 50 nM (isothermal titration calorimetry). Crystals of human
      arginase I complexed with NOHA and nor-NOHA afford 2.04 and 1.55 A resolution
      structures, respectively, which are significantly improved in comparison with
      previously-determined structures of the corresponding complexes with rat arginase
      I. Higher resolution structures clarify the binding interactions of the
      inhibitors. Finally, the crystal structure of the complex with L-lysine (K(d)=13
      microM) is reported at 1.90 A resolution. This structure confirms the importance
      of hydrogen bond interactions with inhibitor alpha-carboxylate and alpha-amino
      groups as key specificity determinants of amino acid recognition in the arginase
      active site.

PMID- 20153714
TI  - Characterizing the effect of nitrosative stress in Saccharomyces cerevisiae.
AB  - Nitrosative stress has various pathophysiological implications. We here present a
      detailed characterization on the effect of nitrosative stress in Saccharomyces
      cerevisiae wild-type (Y190) and its isogenic flavohemoglobin mutant (Deltayhb1)
      strain grown in presence of non fermentable carbon source. On addition of sub
      toxic dose of nitrosating agent both the strains showed microbiostatic effect.
      Cellular respiration was found to be significantly affected in both the strains
      in presence sodium nitroprusside. Although there was no alteration in
      mitochondrial permeability potential changes and reactive oxygen species
      production in both the strains but the cellular redox status is differentially
      regulated in Deltayhb1 strain both in cytosol and in mitochondria indicating
      cellular glutathione is the major player in absence of flavohemoglobin. We also
      found important role(s) of various redox active enzymes like glutathione
      reductase and catalase in protection against nitrosative stress. This is the
      first report of its kind where the effect of nitrosative stress has been
      evaluated in S. cerevisiae cytosol as well as in mitochondria under respiratory
      proficient conditions.

PMID- 20153715
TI  - 1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT
      human keratinocytes.
AB  - Selected biological effects of 1,4-naphthoquinone, menadione (2-methyl-1,4
      naphthoquinone) and structurally related quinones from natural sources--the 5
      hydroxy-naphthoquinones juglone, plumbagin and the 2-hydroxy-naphthoquinones
      lawsone and lapachol--were studied in human keratinocytes (HaCaT). 1,4
      naphthoquinone and menadione as well as juglone and plumbagin were highly
      cytotoxic, strongly induced reactive oxygen species (ROS) formation and depleted
      cellular glutathione. Moreover, they induced oxidative DNA base damage and
      accumulation of DNA strand breaks, as demonstrated in an alkaline DNA unwinding
      assay. Neither lawsone nor lapachol (up to 100 microM) were active in any of
      these assays. Cytotoxic and oxidative action was paralleled by stimulation of
      stress signaling: all tested quinones except lawsone and lapachol strongly
      induced phosphorylation of the epidermal growth factor receptor (EGFR) and the
      related ErbB2 receptor tyrosine kinase. EGFR activation by plumbagin, juglone and
      menadione was attenuated by a superoxide dismutase mimetic, indicating that ROS
      related mechanisms contribute to EGFR activation by these naphthoquinones.

PMID- 20153717
TI  - Hypoxia and mitochondrial oxidative metabolism.
AB  - It is now clear that mitochondrial defects are associated with a large variety of
      clinical phenotypes. This is the result of the mitochondria's central role in
      energy production, reactive oxygen species homeostasis, and cell death. These
      processes are interdependent and may occur under various stressing conditions,
      among which low oxygen levels (hypoxia) are certainly prominent. Cells exposed to
      hypoxia respond acutely with endogenous metabolites and proteins promptly
      regulating metabolic pathways, but if low oxygen levels are prolonged, cells
      activate adapting mechanisms, the master switch being the hypoxia-inducible
      factor 1 (HIF-1). Activation of this factor is strictly bound to the
      mitochondrial function, which in turn is related with the oxygen level. Therefore
      in hypoxia, mitochondria act as [O2] sensors, convey signals to HIF-1 directly or
      indirectly, and contribute to the cell redox potential, ion homeostasis, and
      energy production. Although over the last two decades cellular responses to low
      oxygen tension have been studied extensively, mechanisms underlying these
      functions are still indefinite. Here we review current knowledge of the
      mitochondrial role in hypoxia, focusing mainly on their role in cellular energy
      and reactive oxygen species homeostasis in relation with HIF-1 stabilization. In
      addition, we address the involvement of HIF-1 and the inhibitor protein of F1F0
      ATPase in the hypoxia-induced mitochondrial autophagy.

PMID- 20153716
TI  - Cholesterol and peroxidized cardiolipin in mitochondrial membrane properties,
      permeabilization and cell death.
AB  - Mitochondria are known to actively regulate cell death with the final phenotype
      of demise being determined by the metabolic and energetic status of the cell.
      Mitochondrial membrane permeabilization (MMP) is a critical event in cell death,
      as it regulates the degree of mitochondrial dysfunction and the release of
      intermembrane proteins that function in the activation and assembly of caspases.
      In addition to the crucial role of proapoptotic members of the Bcl-2 family, the
      lipid composition of the mitochondrial membranes is increasingly recognized to
      modulate MMP and hence cell death. The unphysiological accumulation of
      cholesterol in mitochondrial membranes regulates their physical properties,
      facilitating or impairing MMP during Bax and death ligand-induced cell death
      depending on the level of mitochondrial GSH (mGSH), which in turn regulates the
      oxidation status of cardiolipin. Cholesterol-mediated mGSH depletion stimulates
      TNF-induced reactive oxygen species and subsequent cardiolipin peroxidation,
      which destabilizes the lipid bilayer and potentiates Bax-induced membrane
      permeabilization. These data suggest that the balance of mitochondrial
      cholesterol to peroxidized cardiolipin regulates mitochondrial membrane
      properties and permeabilization, emerging as a rheostat in cell death.

PMID- 20153718
TI  - Pore-forming properties of the Bacillus thuringiensis toxin Cry9Ca in Manduca
      sexta brush border membrane vesicles.
AB  - The toxicity and pore-forming ability of the Bacillus thuringiensis Cry9Ca
      insecticidal toxin, its single-site mutants, R164A and R164K, and the 55-kDa
      fragment resulting from its proteolytic cleavage at residue 164 were investigated
      using Manduca sexta neonate larvae and fifth-instar larval midgut brush border
      membrane vesicles, respectively. Neither the mutations nor the proteolytic
      cleavage altered Cry9Ca toxicity. Compared with Cry1Ac, Cry9Ca and its mutants
      formed large poorly selective pores in the vesicles. Pore formation was highly
      dependent on pH, however, especially for wild-type Cry9Ca and both mutants.
      Increasing pH from 6.5 to 10.5 resulted in an irregular step-wise decrease in
      membrane permeabilization that was not related to a change in the ionic
      selectivity of the pores. Pore formation was much slower with Cry9Ca and its
      derivatives, including the 55-kDa fragment, than with Cry1Ac and its rate was not
      influenced by the presence of protease inhibitors or a reducing agent.

PMID- 20153719
TI  - Erythrocyte death in vitro induced by starvation in the absence of Ca(2+).
AB  - Human erythrocytes (RBCs), stored at 4 degrees C under nominal absence of
      external energy sources and calcium ions, show a gradual decrease in membrane
      roughness (R(rms)) at the end of which the appearance of morphological phenomena
      (spicules, vesicles and spherocytes) is observed on the cell membrane, phenomena
      that can mainly be ascribed to the ATP-dependent disconnection of the cortical
      cytoskeleton from the lipid bilayer. After depletion of the intracellular energy
      sources obtained under the extreme conditions chosen, treatment with a minimal
      rejuvenation solution makes the following remarks possible: (i) RBCs are able to
      regenerate adenosine triphosphate (ATP) and 2,3-bisphosphoglycerate only up to 4
      days of storage at 4 degrees C, whereas from the eighth day energy stocks cannot
      be replenished because of a disorder in the transmembrane mechanisms of
      transport; (ii) the RBCs' roughness may be restored to the initial value (i.e.
      that observed in fresh RBCs) only in samples stored up to 4-5 days, whereas after
      the eighth day of storage the rejuvenation procedure appears to be inefficient;
      (iii) membrane physical properties - as measured by R(rms) - are actually
      controlled by the metabolic production of ATP, necessary to perform the RBCs'
      basic functions; (iv) once energy stores cannot be replenished, a regulated
      sequence of the morphological events (represented by local buckles that lead to
      formation of spicules and vesicles of the lipid bilayer with generation of
      spherocytes) is reminiscent of the RBCs' apoptotic final stages; (v) the
      morphological phenomenology of the final apoptotic stages is passive (i.e.
      determined by simple mechanical forces) and encoded in the mechanical properties
      of the membrane-skeleton; and (vi) necrotic aspects (e.g. disruption of cell
      membrane integrity, so that intracellular protein content is easily released)
      ensue when RBCs are almost totally (> or =90%) depleted in an irreversible way of
      the energetic stores.

PMID- 20153720
TI  - Influence of the nature of the sterol on the behavior of palmitic acid/sterol
      mixtures and their derived liposomes.
AB  - The phase behavior of mixtures formed with palmitic acid (PA) and one of the
      following sterols (dihydrocholesterol, ergosterol, 7-dehydrocholesterol,
      stigmasterol and stigmastanol), in a PA/sterol molar ratio of 3/7, has been
      characterized by IR and (2)H NMR spectroscopy at different pH. Our study shows
      that it is possible to form liquid-ordered (lo) lamellar phases with these binary
      non-phospholipid mixtures. The characterization of alkyl chain dynamics of PA in
      these systems revealed the large ordering effect of the sterols. It was possible
      to extrude these systems, using standard extrusion techniques, to form large
      unilamellar vesicles (LUVs), except in the case of ergosterol-containing mixture.
      The resulting LUVs displayed a very limited passive permeability consistent with
      the high sterol concentration. In addition, the stability of these PA/sterol self
      assembled bilayers was also found to be pH-sensitive, therefore, potentially
      useful as nanovectors. By examining different sterols, we could establish some
      correlations between the structure of these bilayers and their permeability
      properties. The structure of the side chain at C17 of the sterol appears to play
      a prime role in the mixing properties with fatty acid.

PMID- 20153721
TI  - Phosphorylated SAP155, the spliceosomal component, is localized to chromatin in
      postnatal mouse testes.
AB  - SAP155 is an essential component of the spliceosome and its phosphorylation is
      required for splicing catalysis, but little is known concerning its expression
      and regulation during spermatogenesis in postnatal mouse testes. We report that
      SAP155 is ubiquitously expressed in nuclei of germ and Sertoli cells within the
      seminiferous tubules of 6- and 35-day postpartum (dpp) testes. Analyses by
      fractionation of testes revealed that (1) phosphorylated SAP155 was found in the
      fraction containing nuclear structures at 6 dpp in amounts much larger than that
      at other ages; (2) non-phosphorylated SAP155 was detected in the fraction
      containing nucleoplasm; and (3) phosphorylated SAP155 was preferentially
      associated with chromatin. Our findings suggest that the active spliceosome,
      containing phosphorylated SAP155, performs pre-mRNA splicing on chromatin
      concomitant with transcription during testicular development.

PMID- 20153722
TI  - MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis
      and eNOS activity.
AB  - Mechanical forces associated with blood flow play an important role in regulating
      vascular signaling and gene expression in endothelial cells (ECs). MicroRNAs
      (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the
      expression of genes involved in diverse cell functions, including
      differentiation, growth, proliferation, and apoptosis. miRNAs are known to have
      an important role in modulating EC biology, but their expression and functions in
      cells subjected to shear stress conditions are unknown. We sought to determine
      the miRNA expression profile in human ECs subjected to unidirectional shear
      stress and define the role of miR-21 in shear stress-induced changes in EC
      function. TLDA array and qRT-PCR analysis performed on HUVECs exposed to
      prolonged unidirectional shear stress (USS, 24h, 15 dynes/cm(2)) identified 13
      miRNAs whose expression was significantly upregulated (p<0.05). The miRNA with
      the greatest change was miR-21; it was increased 5.2-fold (p=0.002) in USS
      treated versus control cells. Western analysis demonstrated that PTEN, a known
      target of miR-21, was downregulated in HUVECs exposed to USS or transfected with
      pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and
      increased eNOS phosphorylation and nitric oxide (NO(*)) production. These data
      demonstrate that shear stress forces regulate the expression of miRNAs in ECs,
      and that miR-21 influences endothelial biology by decreasing apoptosis and
      activating the NO(*) pathway. These studies advance our understanding of the
      mechanisms by which shear stress forces modulate vascular homeostasis.

PMID- 20153723
TI  - Ly49Q, an ITIM-bearing NK receptor, positively regulates osteoclast
      differentiation.
AB  - Osteoclasts, multinucleated cells that resorb bone, play a key role in bone
      remodeling. Although immunoreceptor tyrosine-based activation motif (ITAM)
      mediated signaling is critical for osteoclast differentiation, the significance
      of immunoreceptor tyrosine-based inhibitory motif (ITIM) has not been well
      understood. Here we report the function of Ly49Q, an Ly49 family member
      possessing an ITIM motif, in osteoclastogenesis. Ly49Q is selectively induced by
      receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)
      stimulation in bone marrow-derived monocyte/macrophage precursor cells (BMMs)
      among the Ly49 family of NK receptors. The knockdown of Ly49Q resulted in a
      significant reduction in the RANKL-induced formation of tartrate-resistance acid
      phosphatase (TRAP)-positive multinucleated cells, accompanied by a decreased
      expression of osteoclast-specific genes such as Nfatc1, Tm7sf4, Oscar, Ctsk, and
      Acp5. Osteoclastogenesis was also significantly impaired in Ly49Q-deficient cells
      in vitro. The inhibitory effect of Ly49Q-deficiency may be explained by the
      finding that Ly49Q competed for the association of Src-homology domain-2
      phosphatase-1 (SHP-1) with paired immunoglobulin-like receptor-B (PIR-B), an ITIM
      bearing receptor which negatively regulates osteoclast differentiation.
      Unexpectedly, Ly49Q deficiency did not lead to impaired osteoclast formation in
      vivo, suggesting the existence of a compensatory mechanism. This study provides
      an example in which an ITIM-bearing receptor functions as a positive regulator of
      osteoclast differentiation.

PMID- 20153724
TI  - Daxx is reciprocally regulated by Mdm2 and Hausp.
AB  - Daxx is a multifunctional protein, regulating a wide range of important functions
      including apoptosis and transcription. However, the way Daxx is regulated is
      poorly understood. In our previous studies, we have found that Daxx forms a
      complex with the E3 ubiquitin ligase Mdm2 and the de-ubiquitinase Hausp. In the
      present work, we show that Daxx is ubiquitinated by Mdm2 in both in vitro and in
      vivo systems and Mdm2 reduces Daxx expression upon over-expression. We further
      demonstrate that Hausp critically controls the cellular level of Daxx most likely
      by inducing Daxx de-ubiquitination. These results reveal Mdm2 and Hausp as
      important regulators for Daxx functions by controlling Daxx ubiquitination and
      stability.

PMID- 20153725
TI  - Nonmuscle myosin II localization is regulated by JNK during Drosophila larval
      wound healing.
AB  - We investigated cell shape changes during wound closure in the Drosophila larval
      epidermis. During reepithelialization, epidermal cells permanently change shape
      from pentagonal or hexagonal to irregular forms. This process requires zipper, a
      gene encoding the Drosophila nonmuscle myosin II heavy chain. Following wounding,
      myosin II is localized at the wound margin and at the rear end of individual
      cells located within several rows from the wound hole. The c-Jun N-terminal
      kinase (JNK) pathway is essential for this myosin II localization. These results
      suggest that not only the wound leading edge but also the cells lying distal to
      the leading edge cells actively participate in epithelial cell sheet migration
      during wound hole closure.

PMID- 20153726
TI  - Alpha-lipoic acid inhibits hepatic PAI-1 expression and fibrosis by inhibiting
      the TGF-beta signaling pathway.
AB  - Accumulating evidence suggests that plasminogen activator inhibitor (PAI)-1 plays
      an important role in the development of hepatic fibrosis via its involvement in
      extracellular matrix remodeling. We previously reported that alpha-lipoic acid
      (ALA), a naturally occurring thiol antioxidant, prevents hepatic steatosis by
      inhibiting the expression of sterol regulatory element binding protein-1c. The
      aim of the present study was to determine whether ALA prevents hepatic PAI-1
      expression and fibrosis through the inhibition of multiple TGF-beta-mediated
      molecular mediators. We investigated whether ALA inhibited the development of
      hepatic fibrosis in mice following bile duct ligation (BDL), an established
      animal model of liver fibrosis. We found that ALA markedly inhibited BDL-induced
      hepatic fibrosis and PAI-1 expression. We also found that ALA attenuated TGF-beta
      stimulated PAI-1 mRNA expression, and inhibited PAI-1 promoter activity in liver
      cells; this effect was mediated by Smads and the JNK and ERK pathways. The
      results of the present study indicate that ALA inhibits hepatic PAI-1 expression
      through inhibition of TGF-beta-mediated molecular mediators, including Smad3,
      AP1, and Sp1, and prevents the development of BDL-induced hepatic fibrosis. These
      findings suggest that ALA may have a clinical application in preventing the
      development and progression of hepatic fibrosis.

PMID- 20153727
TI  - The immunological and chemical detection of N-(hexanoyl)phosphatidylethanolamine
      and N-(hexanoyl)phosphatidylserine in an oxidative model induced by carbon
      tetrachloride.
AB  - Lipid peroxidation products have a high reactivity against the primary amino
      groups of biomolecules such as aminophospholipids, proteins, and DNA. Until now,
      many papers have reported about the modification of biomolecules derived from
      lipid peroxides. Our group has also reported that aminophospholipids, such as
      phosphatidylethanolamine (PE), can be modified by lipid peroxidation including 13
      hydroperoxyoctadecadienoic acid (13-HPODE). The aim of this study was to examine
      the oxidative stress in vivo by detecting the formation of N
      (hexanoyl)phosphatidylethanolamine (HEPE) and N-(hexanoyl)phosphatidylserine
      (HEPS), a novel hexanoyl adduct, using a liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) and a monoclonal antibody. Consequently, we observed that
      the formation of HEPE and HEPS occurred in the red blood cell (RBC) ghosts
      modified by 13-HPODE and the oxidative stress model induced by carbon
      tetrachloride (CCl(4)) using LC/MS/MS monitoring hexanoyl ethanolamine (HEEA), a
      head group of HEPE, and hexanoyl serine (HESE) as a part of HEPS. Furthermore, we
      obtained a novel type of monoclonal antibody against HEPE. This antibody could
      recognize HEPE in the liver of rats with oxidative stress in vivo.

PMID- 20153728
TI  - Spred2 is involved in imatinib-induced cytotoxicity in chronic myeloid leukemia
      cells.
AB  - Spreds, a recently established class of negative regulators of the Ras-ERK
      (extracellular signal-regulated kinase) pathway, are involved in hematogenesises,
      allergic disorders and tumourigenesis. However, their role in hematologic
      neoplasms is largely unknown. Possible effects of Spreds on other signal pathways
      closely related to Ras-ERK have been poorly investigated. In this study, we
      investigated the in vitro effects of Spred2 on chronic myeloid leukemia (CML)
      cells. In addition to inhibiting the well-established Ras-ERK cascade, adenovirus
      mediated Spred2 over-expression inhibits constitutive and stem cell factor (SCF)
      stimulated sphingosine kinase-1 (SPHK1) and Mcl-1 expression, as well as
      inhibiting proliferation and inducing apoptosis in CML cells. In K562 cells and
      primary CML cells, imatinib induces endogenous Spred2 expression. Spred2
      silencing by stable RNA interference partly protects K562 cells against imatinib
      induced apoptosis. Together, these data implicate Spred2 in imatinib-induced
      cytotoxicity in CML cells, possibly by inhibiting the Ras-ERK cascade and the pro
      survival signaling molecules SPHK1 and Mcl-1. These findings reveal potential
      targets for selective therapy of CML.

PMID- 20153729
TI  - Hypoxia-reoxygenation increase invasiveness of PANC-1 cells through Rac1/MMP-2.
AB  - Pancreatic cancer is an aggressive malignancy with proclivity to early
      metastasis. High expression and activation of the collagenase matrix
      metalloproteinase-2 (MMP-2) have been found in human pancreatic cancer tissues,
      being these increased levels of active MMP-2 correlated to tumor invasion and
      metastasis. Hypoxia and reoxygenation (H-R) are critical pathophysiological
      conditions during ischemia-reperfusion injury, which has been shown to enhance
      both invasion and metastasis. In the present study, we investigated the effects
      of H-R on MMP-2 levels and the invasiveness properties of human pancreatic cancer
      cells PANC-1. Using specific inhibitors, we found that H-R treatment of these
      tumor cells induced secretion and activation of MMP-2, which was required for H-R
      stimulated basement membrane degradation and cell invasion. Our results also
      indicate that signaling events involved in H-R-enhanced PANC-1 invasiveness
      comprehend PI3K-dependent activation of Rac1, which mediated the formation of
      NADPH-generated reactive oxygen species responsible for MMP-2 secretion and
      activation.

PMID- 20153730
TI  - Biochemical analysis of Lgt3, a glycosyltransferase of the bacterium Moraxella
      catarrhalis.
AB  - The lipooligosaccharide (LOS) of Moraxella catarrhalis is unusual in that it
      lacks heptose. The sugar linking oligosaccharide to Lipid A is a trisubstituted
      glucose. A single enzyme, Lgt3, is suggested to trisubstitute this core sugar.
      The lgt3 gene encodes two distinct domains with high similarity to
      glucosyltransferases of the GT-A superfamily, thus encoding a bidomain,
      multifunctional glucosyltransferase. To characterise Lgt3, the gene was amplified
      from M. catarrhalis, expressed in Escherichia coli, and purified. Analysis of its
      glycosyltransferase catalytic activity ascertained the pH and temperature optima
      for Lgt3. The donor specificity and acceptor specificity were examined. This
      study confirms that Lgt3 is a glucosyltransferase which catalyses addition of
      glucose to its cognate receptor, a terminal glucose presented as the core region
      of LOS.

PMID- 20153731
TI  - Bioaccumulation and toxicity of gold nanoparticles after repeated administration
      in mice.
AB  - Gold nanoparticles (GNPs) offer a great promise in biomedicine. Currently, there
      is no data available regarding the accumulation of nanoparticles in vivo after
      repeated administration. The purpose of the present study was to evaluate the
      bioaccumulation and toxic effects of different doses (40, 200, and 400
      microg/kg/day) of 12.5 nm GNPs upon intraperitoneal administration in mice every
      day for 8 days. The gold levels in blood did not increase with the dose
      administered, whereas in all the organs examined there was a proportional
      increase on gold, indicating efficient tissue uptake. Although brain was the
      organ containing the lowest quantity of injected GNPs, our data suggest that GNPs
      are able to cross the blood-brain barrier and accumulate in the neural tissue.
      Importantly, no evidence of toxicity was observed in any of the diverse studies
      performed, including survival, behavior, animal weight, organ morphology, blood
      biochemistry and tissue histology. The results indicate that tissue accumulation
      pattern of GNPs depend on the doses administered and the accumulation of the
      particles does not produce sub-acute physiological damage.

PMID- 20153732
TI  - Myeloperoxidase increased cardiomyocyte protein nitration in mice subjected to
      nonlethal mechanical trauma.
AB  - Nonlethal mechanical trauma causes cardiomyocyte apoptosis which contributes to
      posttraumatic cardiac dysfunction. Apoptosis is positively correlated with
      protein nitration in the traumatic heart. However, the mechanisms responsible for
      the cardiomyocyte protein nitration remain unclear. The present study was
      designed to identify whether myeloperoxidase may contribute to protein nitration
      in nonlethal mechanical trauma and subsequent cardiomyocyte apoptosis, and, if
      so, to determine the possible mechanisms responsible. We used Noble-Collip drum
      to make nonlethal traumatic mice models. Male adult C57B16/J mice were placed in
      the Noble-Collip drum and subjected to a total of 200 revolutions at a rate of 40
      r/min. Then myeloperoxidase activity and release, protein nitration,
      cardiomyocyte apoptosis, endothelial function and intercellular adhesion molecule
      1 expression were determined. Nonlethal mechanical trauma was characterized by
      the 100% survival rate during the first 24 h after trauma, the lack of
      circulatory shock and without direct heart injury. However, myeloperoxidase
      activity significantly increased 6 h after trauma, and reached a maximum level 12
      h after trauma. Obviously, protein nitration and cardiomyocyte apoptosis
      increased 12h after trauma and could be blocked by administration of R15.7, a
      monoclonal antibody that blocks polymorphonuclear neutrophils adhesion. Moreover,
      endothelial dysfunction and intercellular adhesion molecule-1 upregulation were
      observed in traumatic mice. Our present study demonstrated for the first time
      that myeloperoxidase caused protein nitration and cardiomyocyte apoptosis in
      nonlethal traumatic mice. Inhibition of polymorphonuclear neutrophils adhesion
      and antinitration treatments may be novel measures in reducing posttraumatic
      cardiomyocyte apoptosis and secondary heart injury.

PMID- 20153733
TI  - Abnormal expression and spatiotemporal change of Slit2 in neurons and astrocytes
      in temporal lobe epileptic foci: A study of epileptic patients and experimental
      animals.
AB  - Repellent guidance molecules provide targeting information to outgrowing axons
      along predetermined pathways during development. These molecules may also play a
      role in synaptic reorganization in the adult brain and thereby promote
      epileptogenesis. Our aim was to investigate the expression of Slit2, one of
      repellent guidance molecules, in temporal lobe epileptic foci from epileptic
      patients and experimental animals. Thirty-five temporal neocortex tissue samples
      from patients with intractable temporal lobe epilepsy (TLE) and fifteen
      histological normal temporal lobes from controls were selected. Fifty-four
      Sprague-Dawley rats were divided randomly into six groups, including five groups
      with epilepsy induced by lithium-pilocarpine administration and one control
      group. Temporal lobe tissue samples were taken from rats at 1, 7, 14, 30, and 60
      days post-seizure and from controls. Expression of Slit2 was assessed by
      immunohistochemistry, immunofluorescence, and Western blot analysis. Slit2 was
      mainly expressed in neurons in human controls and in both neurons and astrocytes
      in TLE patients. Slit2 expression was significantly higher in TLE patients as
      compared with the controls. Slit2-positive cells were mainly neurons in the rat
      temporal lobe tissues of the control group, the acute period group, and the
      latent period group, while the Slit2-positive cells were mainly astrocytes in
      chronic phase. Compared with controls, Slit2 expression in animals in the TLE
      group gradually decreased from days 1 to 14 post-seizure, but then increased over
      the levels seen in controls, to peak levels at days 30 and 60. These results
      suggest that Slit2 may play an important role in the pathogenesis of TLE.

PMID- 20153734
TI  - Enhanced expression of the neuronal K+/Cl- cotransporter, KCC2, in spontaneously
      depressed Flinders Sensitive Line rats.
AB  - We used Flinder Sensitive Line (FSL) rats, a genetic model of unipolar
      depression, to examine whether changes in central GABAergic transmission are
      associated with a depressed phenotype. FSL rats showed an increased behavioral
      response to low doses of diazepam, as compared to either Sprague Dawley (SD) or
      Flinder Resistant Line (FRL) rats used as controls. Diazepam at a dose of 0.3
      mg/kg, i.p., induced a robust impairment of motor coordination in FSL rats, but
      was virtually inactive in SD or FRL rats. The increased responsiveness of FSL
      rats was not due to changes in the brain levels of diazepam or its active
      metabolites, or to increases in the number or affinity of benzodiazepine
      recognition sites, as shown by the analysis of [(3)H]-flunitrazepam binding in
      the hippocampus, cerebral cortex or cerebellum. We therefore examined whether FSL
      rats differed from control rats for the expression levels of the K(+)/Cl(-)
      cotransporter, KCC2, which transports Cl(-) ions out of neurons, thus creating
      the concentration gradient that allows Cl(-) influx through the anion channel
      associated with GABA(A) receptors. Combined immunoblot and immunohistochemical
      data showed a widespread increase in KCC2 expression in FSL rats, as compared
      with control rats. The increase was more prominent in the cerebellum, where KCC2
      was largely expressed in the granular layer. These data raise the interesting
      possibility that a spontaneous depressive state in animals is associated with an
      amplified GABAergic transmission in the CNS resulting from an enhanced expression
      of KCC2.

PMID- 20153735
TI  - Metabotropic glutamate receptors modulate glutamatergic and GABAergic synaptic
      transmission in the central nucleus of the inferior colliculus.
AB  - Fast glutamatergic and GABAergic transmission in the central nucleus of the
      inferior colliculus (ICC), a major auditory midbrain structure, is mediated
      respectively by alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid (AMPA)
      and gamma-aminobutyric acid (GABA)(A) receptors. In this study, we used whole
      cell patch clamp recordings in brain slices to investigate the effects of
      activation of metabotropic glutamate receptors (mGluRs) on synaptic responses
      mediated by AMPA and GABA(A) receptors in ICC neurons of young rats. Excitatory
      and inhibitory postsynaptic currents (EPSCs and IPSCs) mediated respectively by
      AMPA and GABA(A) receptors were elicited by stimulation of the lateral lemniscus,
      the major afferent pathway to the ICC. The agonists for groups I and II mGluRs,
      (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD), and for group III
      mGluRs, L-2-amino-3-hydroxypropanoic acid 3-phosphate (L-SOP), did not affect
      intrinsic membrane properties of the ICC neurons. The agonist for group II
      mGluRs, (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0] hexane-4,6-dicarboxylic acid
      (LY379268), significantly reduced the AMPA receptor-mediated EPSCs and GABA(A)
      receptor-mediated IPSCs. The effects were reversed by the group II mGluR
      antagonist, (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)
      propanoic acid (LY341495). The agonists for groups I and III, (RS)-3,5
      dihydroxyphenylglycine (DHPG) and L-SOP, respectively, did not affect AMPA or
      GABA(A) receptor-mediated responses. The reduction of the synaptic responses by
      LY379268 was accompanied by a substantial increase in a ratio of the second to
      the first AMPA receptor-mediated EPSCs and GABA(A) receptor-mediated IPSCs to
      paired-pulse stimulation. The results suggest that group II mGluRs regulate both
      fast glutamatergic and GABAergic synaptic transmission in the ICC, probably
      through a presynaptic mechanism due to reduction of transmitter release.

PMID- 20153736
TI  - Hypoxic preconditioning provides neuroprotection and increases vascular
      endothelial growth factor A, preserves the phosphorylation of Akt-Ser-473 and
      diminishes the increase in caspase-3 activity in neonatal rat hypoxic-ischemic
      model.
AB  - Vascular endothelial growth factor A (VEGF) likely plays a role in the hypoxic
      preconditioning (PC) induced tolerance to subsequent hypoxic-ischemic (HI) injury
      to the brain. However, limited data is available concerning VEGF in the
      developing brain after HI following PC. Neuroprotection by VEGF involves
      activation of Akt which inhibits apoptotic processes that contribute
      significantly to the brain injury in neonatal HI. We evaluated whether PC
      provides neuroprotection and affects VEGF, Akt and caspase-3 following HI in the
      developing rat brain. Newborn rats (6 days) were subjected to normoxia (21% O(2))
      or PC (8% O(2)) for 3h followed by 24h of reoxygenation. The rats then had the
      right carotid artery permanently ligated followed by 140 min of hypoxia (8% O(2))
      (HI or PC+HI). Brains from rats at the corresponding age without any exposure to
      PC or HI were examined for comparison (Sham). PC significantly reduced brain
      damage as measured by weight loss of the right hemisphere at 22 days after HI and
      by gross and microscopic morphology. PC amplified and prolonged the induction of
      mRNA of VEGF splice variants measured by real-time RT-PCR and enhanced the
      increase in VEGF protein measured by ELISA in brain following HI. PC preserved
      the phosphorylation of Akt-Ser-473 and diminished the increase in caspase-3
      activity in brain following HI. We conclude that PC provides neuroprotection and
      augments and preserves the increase in VEGF following HI in the newborn rat brain
      which may play an important role in neuroprotection.

PMID- 20153737
TI  - Alpha-ketoisocaproic acid and leucine provoke mitochondrial bioenergetic
      dysfunction in rat brain.
AB  - Patients affected by maple syrup urine disease (MSUD) present severe neurological
      symptoms and brain abnormalities, whose pathophysiology is poorly known. In the
      present study we investigated the in vitro effects of leucine (Leu), alpha
      ketoisocaproic acid (KIC) and alpha-hydroxyisovaleric acid (HIV), respectively,
      the branched-chain amino, keto and hydroxy acids that most accumulate in MSUD, on
      brain bioenergetic homeostasis, evaluating respiratory parameters obtained by
      oxygen consumption, membrane potential (Psim), NAD(P)H content, swelling and
      citric acid cycle enzyme activities in mitochondrial preparations from rat
      forebrain using glutamate plus malate, succinate or alpha-ketoglutarate as
      respiratory substrates. KIC increased state 4 and decreased the respiratory
      control ratio with all substrates, in contrast with Leu and HIV. Furthermore, KIC
      and Leu, but not HIV, decreased state 3 using alpha-ketoglutarate. A KIC-induced
      selective inhibition of alpha-ketoglutarate dehydrogenase activity was also
      verified, with no alteration of the other citric acid cycle activities. The ADP/O
      ratio and the mitochondrial NAD(P)H levels were also reduced by KIC using
      glutamate/malate and alpha-ketoglutarate. In addition, KIC caused a reduction in
      the Psim when alpha-ketoglutarate was the substrate. Finally, KIC was not able to
      induce mitochondrial swelling. The present data indicate that KIC acts as an
      uncoupler of oxidative phosphorylation and as a metabolic inhibitor possibly
      through its inhibitory effect on alpha-ketoglutarate dehydrogenase activity,
      while Leu acts as a metabolic inhibitor. It is suggested that impairment of
      mitochondrial homeostasis caused by the major metabolites accumulating in MSUD
      may be involved in the neuropathology of this disease.

PMID- 20153738
TI  - Differential influence of non-synaptic mechanisms in two in vitro models of
      epileptic field bursts.
AB  - Non-synaptic interactions are known to promote epileptiform activity through
      mechanisms that have primarily been studied in one particular in vitro model (low
      Ca(2+) model). Here we characterize another non-synaptic model, where ictal-like
      field bursts are induced in the CA1 area of rat hippocampal slices by exposure to
      Cs(+) (4-5mM) together with blockers of fast chemical synaptic transmission, and
      compare it with the low Ca(2+) model. The Cs-induced field bursts were blocked by
      1 microM tetrodotoxin, but persisted in the presence of 200 microM Cd(2+) or 300
      microM Ni(2+). Hyperosmotic condition (addition of 30 mM sucrose), reduced burst
      amplitude, but, unlike field bursts induced by 0mM Ca(2+)/5.25 mM K(+), sucrose
      had no effect on frequency or duration. Intracellular alkalinization
      acidification sequence induced by NH(4)Cl potentiated and blocked, respectively,
      the field bursts. Octanol (100-250 microM) blocked all activity in most
      experiments. A quantitative comparison of three gap junction antagonists
      (carbenoxolone (100 microM), quinidine (100-250 microM), and endothelin-3 (1-2
      microM)) indicated that gap junction communication is implicated in both models.
      However, endothelin-3 had selective effect on the low Ca(2+)-induced field burst.
      The data suggest that extracellular space-dependent processes, including field
      effects, significantly contribute to ongoing field burst activity, whereas
      initiation of a field burst can occur with or without the aid of such
      interactions, depending on the level of neuronal excitability. Gap junctions seem
      to have a general role in initiating field bursts. However, the contribution to
      this effect from neuronal versus glial connexin types differs in the two
      epileptic models studied.

PMID- 20153739
TI  - Regulation of the nicotinic receptor alpha7 subunit by chronic stress and
      corticosteroids.
AB  - The alpha7 subunit of the nicotinic acetylcholine receptor (NAchRalpha7) is one
      of the principal brain receptors for nicotine and is thought to be a mediator of
      nicotine's pro-cognitive effects. While nicotine is known to interact with the
      stress axis, little is known about the effect of stress or corticosteroids on the
      expression in the hippocampus, a brain region important to both cognition and
      stress reactivity. We examined the effects of chronic (21 day) restraint stress
      (CRS) and adrenalectomy with hormone replacement with the selective
      mineralocorticoid receptor (MR) agonist aldosterone, the selective glucocorticoid
      receptor (GR) agonist RU28,362 or corticosterone for 7 days, on the hippocampal
      expression of NAchRalpha7 mRNA and protein, as measured by (125)I alpha
      Bungarotoxin autoradiography. We found that CRS increased the levels of
      NAchRalpha7 mRNA in the CA1, CA3 and dentate gyrus while levels of the protein
      were lowered by the same treatment. Corticosteroid replacement showed a GR
      specific increase in NAchRalpha7 mRNA, consistent with a corticosteroid mediated
      effect of CRS. While the mechanism behind these observations is as yet unclear,
      they may be neuroprotective against the damaging effects of CRS or an example of
      adaptation to the allostatic load produced by CRS.

PMID- 20153740
TI  - Abnormal gene expression in cerebellum of Npc1-/- mice during postnatal
      development.
AB  - Niemann-Pick Type C (NPC) disease is an autosomal recessive neurodegenerative
      disorder with abnormal lipid storage as the major cellular pathologic hallmark.
      Genetic analyses have identified mutations in NPC1 gene in the great majority of
      cases, while mutations in NPC2 account for the remainders. Yet little is known
      regarding the cellular mechanisms responsible for NPC pathogenesis, especially
      for neurodegeneration, which is the usual cause of death. To identify critical
      steps that could account for the pathological manifestations of the disease in
      one of the most affected brain structures, we performed global gene expression
      analysis in the cerebellum from 3-week old Npc1+/+ and Npc1-/- mice with two
      different microarray platforms (Agilent and Illumina). Differentially expressed
      genes identified by both microarray platforms were then subjected to KEGG pathway
      analysis. Expression of genes in six pathways was significantly altered in Npc1-/
      mice; functionally, these signaling pathways belong to the following three
      categories: (1) steroid and terpenoid biosynthesis, (2) immune response, and (3)
      cell adhesion/motility. In addition, the expression of several proteins involved
      in lipid transport was significantly altered in Npc1-/- mice. Our results provide
      novel molecular insight regarding the mechanisms of pathogenesis in NPC disease
      and reveal potential new therapeutic targets.

PMID- 20153741
TI  - Apo(a) phenotyping and long-term prognosis for coronary artery disease.
AB  - OBJECTIVES: Identify whether the plasma concentration of Lp(a), apo(a) size or a
      greater affinity for fibrin predict the likelihood of cardiac death, non-fatal
      myocardial infarction, unstable angina, the need for additional
      revascularization, and stroke (MACCE). DESIGN AND METHODS: We analyzed the
      clinical prognosis of 68 patients with coronary artery disease included in a case
      controlled study which evaluated Lp(a) concentration, apo(a) size, and Lp(a)
      fibrin-binding. Cohort was conducted over a median of 8 years. We used Kaplan
      Meier survival tables to evaluate cardiovascular and cerebrovascular events in
      the follow-up period. RESULTS: Apo(a) isoforms of small size are predictors of
      MACCE. We find an association between Lp(a) concentration and apo(a) fibrin
      binding with major adverse cardiovascular and cerebrovascular events, although
      without statistically significant results. CONCLUSIONS: Small-sized apo(a)
      isoforms are an independent risk factor for MACCE in patients with coronary
      artery disease in follow-up. Lp(a) plasma concentration and apo(a) fibrin-binding
      were associated, although not significant.

PMID- 20153742
TI  - Pediatric reference intervals for immunoglobulin G and its subclasses with
      Siemens immunonephelometric assays.
AB  - OBJECTIVE: To determine the pediatric reference intervals for the Dade Behring
      IgG subclass reagents. DESIGN AND METHODS: Blood samples of healthy children and
      adolescents were analyzed to determine the level of immunoglobulin G (IgG) and
      the IgG subclass using the reagents of Dade Behring Marburg GmbH. RESULTS: The
      reference intervals categorized by age were reported from a total of 436 samples.
      There was an excellent correlation between the total IgG and the sum of the IgG
      subclasses. CONCLUSIONS: Our data provide the missing pediatric reference
      intervals and enable the use of the Dade Behring nephelometric IgG subclass
      reagents in children and adolescents.

PMID- 20153744
TI  - Estrogen represses SOX9 during sex determination in the red-eared slider turtle
      Trachemys scripta.
AB  - Production of male offspring in viviparous eutherian mammals requires a sex
      determining mechanism resistant to maternal hormones. This constraint is relaxed
      in egg-laying species, which are sensitive to hormones during sex determination
      and often use an increase in aromatase, the estrogen-synthesizing enzyme, as a
      key feminizing signal. In the turtle Trachemys scripta, sex is normally
      determined by temperature, but estrogen treatment overrides this cue and leads
      exclusively to female development. We assessed whether the expression of SOX9, a
      central male sex-determining gene in mammals, or three other conserved
      transcription factors (WT1, GATA4, and LHX9) was regulated by estrogen signaling
      in the turtle. As in mice, all somatic cell types in the immature turtle gonad
      initially expressed WT1 and GATA4, whereas SOX9 was restricted to the Sertoli
      precursors and LHX9 to the coelomic epithelium and interstitium. After the
      bipotential period, SOX9 was abruptly down-regulated at the female temperature.
      Strikingly, embryos treated with beta-estradiol at the male temperature lost SOX9
      expression more than two stages earlier than controls, though WT1, GATA4, and
      LHX9 were unaffected. Conversely, inhibition of estrogen synthesis and signaling
      prevented or delayed SOX9 down-regulation at the female temperature. These
      results suggest that endogenous estrogen feminizes the medulla of the bipotential
      turtle gonad by inhibiting SOX9 expression. This mechanism may be involved in the
      male-to-female sex reversal in wild populations exposed to environmental
      estrogens, and is consistent with results showing that the estrogen receptor
      represses Sox9 to block transdifferentiation of granulosa cells into Sertoli-like
      cells in the adult mouse ovary.

PMID- 20153743
TI  - Development and validation of a comprehensive mutation and deletion detection
      assay for SDHB, SDHC, and SDHD.
AB  - BACKGROUND: Lack of sequencing validation and complexity of deletion testing
      hinder genetic diagnosis of SDH-associated paraganglioma/pheochromocytoma.
      METHODS: We developed sequencing assays and multiplex ligation-dependent probe
      amplification (MLPA) deletion detection for SDHB, SDHC and SDHD. Clinical
      performance was validated on 141 blinded samples, previously tested at NIH.
      RESULTS: Sequencing and deletion detection were highly reproducible and agreed
      with previous NIH results in 99.3% and 100%, respectively. CONCLUSIONS: DNA
      sequencing combined with MLPA allows reliable and simplified genotyping of SDHB,
      SDHC and SDHD.

PMID- 20153745
TI  - The putative antidepressant DOV 216,303, a triple reuptake inhibitor, increases
      monoamine release in the prefrontal cortex of olfactory bulbectomized rats.
AB  - The first line of antidepressant treatment nowadays are selective serotonin
      reuptake inhibitors. Although they are relatively safe to use, selective
      serotonin reuptake inhibitors (SSRIs) can induce severe side effects. New
      promising antidepressants may be the triple monoamine reuptake inhibitors, which
      not only enhance serotonin and norepinephrine neurotransmission, but also
      increase brain dopamine levels. Recently it has been shown that one of the triple
      reuptake inhibitors, DOV 216,303 has antidepressant-like effects in the olfactory
      bulbectomy (OBX) model of depression, but the alterations in monoaminergic
      neurotransmission in these animals are still unknown. In the present study we
      investigated not only the effect of acute, but also chronic treatment of DOV
      216,303 in OBX rats on monoamine and metabolite levels. The main results are
      decreased baseline dopamine levels in the prefrontal cortex one day after OBX,
      while 38days after OBX no difference could be observed in monoamine levels after
      vehicle treatment. Treatment with DOV 216,303 leads to increased extracellular
      levels of serotonin and norepinephrine neurotransmission, but also increased
      dopamine levels in OBX animals as well as their controls. This increase could be
      observed after one single administration, but also after chronic treatment.
      However, a DOV 216,303 challenge in chronically treated animals resulted in lower
      monoamine concentrations than the same challenge in untreated animals. More
      research is needed to investigate this seemingly hyporesponsivity to chronic DOV
      216,303 treatment.

PMID- 20153746
TI  - Age-related accumulation of 3-nitrotyrosine and nitro-A2E in human Bruch's
      membrane.
AB  - Age-related macular degeneration (AMD) is a disease leading to severe visual loss
      and legal blindness in the elderly population. The pathophysiology of AMD is
      complex and may include genetic predispositions, accumulation of lipofuscin and
      drusen, local inflammation and neovascularization. Recently four independent
      research groups have identified a commonly inherited variant (Y402H) of the
      complement factor H gene in the genome from different groups of AMD patients. The
      Y402H variant of CFH significantly increases the risk of AMD and links the
      genetics of the disease with inflammation. During inflammation there is
      activation of inducible nitric oxide synthase and release of nitric oxide, which
      in principal could lead to non-enzymatic nitration within extracellular deposits
      and/or intrinsic extracellular matrix protein components of human Bruch's
      membrane. We have identified two biomarkers for non-enzymatic nitration in aged
      human Bruch's membrane, indicative of inflammation, that include 3-nitrotyrosine
      identified in Bruch's membrane preparations and nitrated A2E from the lipid
      soluble extract of the Bruch's membrane preparation. Approximately 30-40 times
      more A2E is observed in samples of the organic soluble extract of lipofuscin
      compared to the extract of Bruch's membrane. It is of interest to note that
      although A2E is a major constituent of RPE lipofuscin, nitrated A2E could not be
      detected in RPE extracts. We show here that nitro-A2E is a specific biomarker of
      nitrosative stress in Bruch's membrane and its concentration correlates directly
      with tissue age.

PMID- 20153747
TI  - Effect of estrogen on electroretinographic responses in streptozotocin-induced
      diabetic female rats.
AB  - The aim of this study is to investigate the effects of estrogen on functional
      changes in the retinas of streptozotocin (STZ)-induced diabetic rats by using an
      electroretinography. Female rats were randomly divided into four treatment
      groups: (1) Control (sham operation and vehicle administration); (2) STZ (sham
      operation and STZ administration); (3) OVX (ovariectomy and vehicle
      administration); and (4) OVX + STZ (ovariectomy and STZ administration). Full
      field electroretinograms (ERGs) were recorded before OVX and STZ administration
      and 4 and 12 weeks after STZ administration. At 4 weeks after STZ administration,
      although there were no differences in the STZ and OVX groups compared with the
      Control group, the amplitude of the cone-response was significantly lower in the
      OVX + STZ group than in the Control group (P = 0.013). At 12 weeks after STZ
      administration, this response showed a similar tendency in the STZ and the OVX +
      STZ groups. At 12 weeks after STZ administration, the implicit times of OP3 and
      OP4 and of the cone-response were significantly delayed in the STZ and OVX + STZ
      groups (OP3: P = 0.030 and 0.050, OP4: P = 0.0060 and 0.0053, cone-response: P =
      0.014 and 0.039), compared with in the Control group. Thus, the retinal functions
      in STZ-induced diabetic female rats were aggravated by OVX. OVX-induced estrogen
      deficiency resulted in earlier changes in the amplitudes of cone-response,
      especially in the diabetes, although this is a transient effect and it is
      difficult to explain. Recognizing the early neurosensory change would enable a
      better understanding of the effect of estrogen in the retina.

PMID- 20153748
TI  - A single parasite gene determines strain-specific protective immunity against
      malaria: the role of the merozoite surface protein I.
AB  - Despite many decades of research, no registered vaccine against the pathogenic
      blood stages of the malaria parasite exists, translating into the loss of many
      hundreds of thousands of young lives each year in tropical Africa. Although many
      parasite proteins have been shown to induce immune responses in the host, proof
      for their induction of protective immunity is still lacking. We previously
      reported a novel genetic approach called linkage group selection (LGS) for rapid
      identification of target antigens of strain-specific protective immunity (SSPI)
      against malaria. In preliminary LGS experiments, we crossed two genetically
      distinct strains of Plasmodium chabaudi chabaudi and subjected their progeny to
      selection in strain-specifically immunised mice, measuring the effects of SSPI
      selection with low coverage/resolution genetic markers. In the present study,
      through application of high coverage/resolution, single nucleotide polymorphism
      (SNP) markers spanning all 14 parasite chromosomes, we analysed 35 SSPI selection
      events on different populations of progeny parasites. Here we report a
      comprehensive high resolution genome-wide analysis of the effects of strain
      specific immune selection on blood stage parasites. Our analyses consistently
      identify a single genomic region spanning approximately 79kb on chromosome 8 as
      the region controlling SSPI. Within this region, one gene (that of merozoite
      surface protein 1, MSP-1) accounted for >60% of genetic polymorphism and was most
      frequently under greatest reduction under SSPI. These results, combined with
      those of an independent LGS analysis of a different genetic cross with different
      parental strains, demonstrate that more than any other locus, the gene for MSP-1
      determines the effect of strain-specific protective immunity against malaria in
      these host-parasite combinations. Our results provide unique insight into the
      precise timing of the parasite killing immune response against progeny parasites
      carrying specific alleles of MSP-1; these findings pave the way for investigating
      which part(s) of this highly polymorphic molecule mediate the protective immune
      response.

PMID- 20153749
TI  - Influence of blood meal on the responsiveness of olfactory receptor neurons in
      antennal sensilla trichodea of the yellow fever mosquito, Aedes aegypti.
AB  - In female Aedes aegypti L. mosquitoes, a blood meal induces physiological and
      behavioral changes. Previous studies have shown that olfactory receptor neurons
      (ORNs) housed in grooved peg sensilla on the antennae of Ae. aegypti down
      regulate their sensitivity to lactic acid, a key component driving host-seeking
      behavior, which correlates with observed changes in the host-seeking behavior of
      this species. In the present study, we performed electrophysiological recordings
      from the most abundant antennal sensillum type, sensilla trichodea. Our results
      indicate that the response spectra of ORNs contained within most trichoid
      sensilla do not change in response to blood feeding. However, we observe an
      increase in sensitivity to primarily indole and phenolic compounds in neurons
      housed within four of the five functional types of short blunt tipped II trichoid
      sensilla, both at 24 and 72h post-blood feeding, which was more pronounced at 24h
      than 72h. Furthermore, sensitivity to undecanone, acetic acid and propionic acid
      was observed to increase 72h post-blood meal. Considering the timing of these
      changes, we believe that these neurons may be involved in driving the orientation
      behavior of female mosquitoes to oviposition sites, which are known to release
      these compounds.

PMID- 20153750
TI  - Evidence for a role of immunoproteasomes in regulating cardiac muscle mass in
      diabetic mice.
AB  - The ubiquitin-proteasome system plays an important role in regulating muscle
      mass. Inducible immunoproteasome subunits LMP-2 and LMP-7 are constitutively
      expressed in the heart; however, their regulation and functions are poorly
      understood. We here investigated the hypothesis that immunoproteasomes regulate
      cardiac muscle mass in diabetic mice. Type 1 diabetes was induced in wildtype
      mice by streptozotocin. After hyperglycemia developed, insulin and the proteasome
      inhibitor epoxomicin were used to treat diabetic mice for 6weeks. Isolated mouse
      hearts were perfused with control or high glucose solution. Catalytic proteasome
      beta-subunits and proteolytic activities were analyzed in the heart by
      immunoblotting and fluorogenic peptide degradation assays, respectively. Insulin
      and epoxomicin blocked loss of heart weight and improved cardiac function in
      diabetic mice. LMP-7 and its corresponding chymotryptic-like proteasome activity
      were increased in diabetic hearts and high glucose-treated hearts. Myosin heavy
      chain protein was decreased in diabetic hearts, which was largely reversed by
      epoxomicin. High glucose decreased LMP-2 protein levels in perfused hearts. In
      diabetic hearts, LMP-2 expression was downregulated whereas expression of the
      phosphatase and tensin homologue deleted on chromosome ten (PTEN) and the muscle
      atrophy F-box were upregulated. Moreover, mice with muscle-specific knockout of
      PTEN gene demonstrated increased cardiac muscle mass, while mice with LMP-2
      deficiency demonstrated PTEN accumulation, muscle mass loss, and contractile
      impairment in the heart. Therefore, we concluded that high glucose regulates
      immunoproteasome subunits and modifies proteasome activities in the heart, and
      that dysregulated immunoproteasome subunits may mediate loss of cardiac muscle
      mass in experimental diabetic mice.

PMID- 20153751
TI  - The antinociceptive effect of acetylsalicylic acid is differently affected by a
      CB1 agonist or antagonist and involves the serotonergic system in rats.
AB  - AIMS: Combinations of non-steroidal anti-inflammatory drugs (NSAIDs) and
      cannabinoids are promising because of their potential synergistic effects in
      analgesia, resulting in a reduction in dosage and minimizing adverse reactions.
      The analgesic effect of acetylsalicylic acid (ASA), probably due to a central
      mechanism, also implicates changes in the central monoaminergic system.
      Therefore, we decided to evaluate the antinociceptive interaction between the
      CB(1) receptor agonist, HU210, and ASA in tests involving central pain in rats as
      well as the implication of the central serotonergic system thereon. MAIN METHODS:
      The selective CB(1) antagonist SR141716A and the potent cannabinoid agonist HU210
      were evaluated alone and in combination with ASA in both algesimetric tests (hot
      plate and formalin tests) and for 5-HT activity and 5-HT(2) receptor density and
      affinity. KEY FINDINGS: ASA or HU210 alone showed a dose-dependent effect in both
      tests. HU210, at an inactive dose, significantly increased the antinociceptive
      effect of the sub-active dose of ASA. SR141716A (1.5mg/kgi.p.) was ineffective
      per se and failed to modify antinociception induced by the HU210 plus ASA
      combination in either test. HU210 plus ASA significantly decreased the 5-HIAA/5
      HT ratio and the 5-HT(2) receptor density in the frontal cortex, changes not
      antagonized by SR141716A. SIGNIFICANCE: The present study provides evidence that
      mutual potentiation of the antinociceptive effects of HU210 and ASA may, at least
      partly, depend on serotonergic mechanisms, with an indirect participation of
      cannabinodiergic mechanism. In conclusion, combinations of low doses of
      cannabinoids and NSAIDs may be of interest from the therapeutic point of view.

PMID- 20153752
TI  - Increased expression of cdk5/p25 in N2a cells leads to hyperphosphorylation and
      impaired axonal transport of neurofilament proteins.
AB  - AIMS: Alzheimer's disease (AD) is the leading cause of dementia. The increased
      cdk5 expression and enhanced phosphorylation of tau and NFs have been seen in AD
      patients. Our study aimed at investigating the effects of increased cdk5 activity
      on axonal transport of neurofilaments (NFs). MAIN METHODS: In this study, we used
      a molecular engineering approach to overexpress cdk5/p25 in neuroblastoma N2a
      cells and investigated the effects on axonal transport with live cell imaging
      techniques. KEY FINDINGS: In stably transfected cells, there was a 2.5-fold
      increase in cdk5 activity compared to non-transfected cells, which in turn led to
      a dramatic increase in phosphorylation of NFs and tau at several phosphorylation
      sites. Using time-lapse imaging technology, the transport of NFs was captured in
      the cells overexpressing cdk5/p25, which were also transiently transfected with
      fluorescence protein linked to the N-terminus of NF-M (EGFP-NFM). The cdk5/p25
      cells displayed significantly slower rates of axonal transport of NFs, with
      accumulation of immobile NF clusters observed in the cell body. Roscovitine, an
      inhibitor of cdk5, significantly reversed this defect in axonal transport.
      SIGNIFICANCE: These results suggest that increased cdk5 activity found in AD
      subjects may be crucially related to the pathogenesis of AD via an underlying
      mechanism by which it promotes accumulation of excessively phosphorylated
      cytoskeletal NF proteins, leading to the enduring impairment of axonal transport
      of NFs.

PMID- 20153753
TI  - Involvement of the nitric oxide/(C)GMP/K(ATP) pathway in antinociception induced
      by exercise in rats.
AB  - AIMS: Physical exercise is responsible for increasing the nociceptive threshold.
      The present study aimed to investigate the involvement of the nitric
      oxide/(C)GMP/K(ATP) pathway in antinociception induced by acute aerobic exercise
      (AAc) in rats. MAIN METHODS: Wistar rats performed exercise in a rodent
      treadmill, according to an AAc protocol. The nociceptive threshold was measured
      by mechanical and thermal nociceptive tests (paw-withdrawal, tail-flick and face
      flick). To investigate the involvement of the NO/(C)GMP/K(ATP) pathway the
      following nitric oxide synthase (NOS) unspecific and specific inhibitors were
      used: N-nitro-l-arginine (NOArg), Aminoguanidine, N(5)-(1-Iminoethyl)-l-ornithine
      dihydrocloride (L-NIO), N(omega)-Propyl-l-arginine (L-NPA); guanylyl cyclase
      inhibitor, 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ); and K(ATP) channel
      blocker, Glybenclamide; all administered subcutaneously at a dose of 2mg/kg 10min
      before exercise started. Plasma and cerebrospinal fluid (CSF) nitrite levels were
      determined by spectrophotometry. KEY FINDINGS: In the paw-withdrawal, tail-flick
      and face-flick tests, the AAc protocol produced antinociception, which lasted for
      more than 15min. This effect was significantly reversed (P<0.05) by NOS specific
      and unspecific inhibitors, guanylyl cyclase inhibitor (ODQ) and K(ATP) channel
      blocker (Glybenclamide). Acute exercise was also responsible for increasing
      nitrite levels in both plasma and cerebrospinal fluid. SIGNIFICANCE: Taken
      together, these results suggest that the NO/(C)GMP/K(ATP) pathway participates in
      antinociception induced by exercise.

PMID- 20153754
TI  - A natural propenoic acid derivative activates peroxisome proliferator-activated
      receptor-beta/delta (PPARbeta/delta).
AB  - AIMS: Previous studies showed that natural prenyloxyphenylpropanoid derivatives
      have potent biological properties in vivo. Given the structural similarities
      between these compounds and known peroxisome proliferator-activated receptor
      (PPAR) agonists, the present study examined the hypothesis that propenoic acid
      derivatives activate PPARs. MAIN METHODS: Chimeric reporter assays were performed
      to identify propenoic acid derivates that could activate PPARs. Quantitative
      polymerase chain reaction (qPCR) analysis of wild-type and Pparbeta/delta-null
      mouse primary keratinocytes was performed to determine if a test compound could
      specifically activate PPARbeta/delta. A human epithelial carcinoma cell line and
      primary mouse keratinocytes were used to determine the effect of the compound on
      cell proliferation. KEY FINDINGS: Three of the propenoic acid derivatives
      activated PPARs, with the greatest efficacy being observed with prenyloxycinnamic
      acid derivatives 4'-geranyloxyferulic acid (compound 1) for PPARbeta/delta.
      Compound 1 increased expression of a known PPARbeta/delta target gene through a
      mechanism that requires PPARbeta/delta. Inhibition of cell proliferation by
      compound 1 was found in a human epithelial carcinoma cell line. SIGNIFICANCE:
      Results from these studies demonstrate that compound 1 can activate
      PPARbeta/delta and inhibit cell proliferation of a human skin cancer cell line,
      suggesting that the biological effects of 4'-geranyloxyferulic acid may be
      mediated in part by activating this PPAR isoform.

PMID- 20153755
TI  - Amphetamine treatment during early postnatal development transiently restricts
      somatic growth.
AB  - AIMS: Restricted somatic growth during fetal or early postnatal periods has been
      suggested to serve as a predictive indicator for neuroanatomical changes and
      behavioral impairments during adulthood. Here, the effects of d-amphetamine
      sulfate (AMPH) exposure during the brain growth spurt period on this potential
      indicator were evaluated. MAIN METHODS: Rats received 0, 5, 15 or 25mg/kg/day of
      AMPH via two daily intragastric intubations from PD4-9. Body weight data were
      collected every other day from PD1 to 21, and then weekly until PD59. On PD9, a
      subset of animals was terminated 90min after the last amphetamine treatment and
      the weights of the cortex, cerebellum, and brainstem were collected. Weights of
      these brain regions from young adult rats were also assessed on PD68. KEY
      FINDINGS: AMPH exposure during early postnatal development limited somatic growth
      in a dose-related manner, with significantly lower body weights in animals
      assigned to the AMPH 25 and AMPH 15 groups. However, this was transient in
      nature, with no significant difference in weight observed after pups were weaned
      on PD21. Further, no differences in brain weight were observed at either age as a
      result of AMPH exposure. SIGNIFICANCE: These findings support the idea that
      developmental AMPH exposure transiently restricts somatic growth. Moreover, the
      lack of effect on brain weight shows that AMPH differentially affects somatic and
      brain growth. The current findings suggest that in addition to the immediate
      effects on body weight, amphetamine may alter the rate of growth, and increase
      the risk for weight-related adult diseases.

PMID- 20153756
TI  - Cholestasis induced nephrotoxicity: the role of endogenous opioids.
AB  - AIMS: Elevated levels of endogenous opioids play a pivotal role in several
      deleterious consequences of cholestasis. Renal dysfunction occurs in cholestasis
      but its exact mechanism is still unknown. In this study, we investigated the role
      of endogenous opioids in cholestasis induced nephrotoxicity. MAIN METHODS: Thirty
      five rats were divided into five groups. In groups 1 and 2 BDL rats received
      either daily subcutaneous 20mg/kg of naltrexone or its vehicle, for 7days after
      BDL. In groups 3 and 4, BDL or Sham rats received no injections. In group 5,
      normal rats received subcutaneous injections of 20mg/kg/day of naltrexone for
      7days. At the 7th day, 24h urine was collected to measure urinary N-acetyl-beta-D
      glucosaminidase (NAG) as an early marker of renal tubular injury. Kidney samples
      were then collected for light and electron microscopic studies. KEY FINDINGS: BDL
      significantly increased NAG activity compared to sham groups. Naltrexone
      significantly reversed NAG activity to normal levels in BDL animals. Naltrexone
      treatment in BDL animals also significantly reversed ALT and AST to their normal
      levels. In light and electron microscopic studies, there were significant
      structural alterations in BDL samples, which were mostly prevented in naltrexone
      treated BDL animals. SIGNIFICANCE: Significant changes in urinary NAG activity
      and renal morphology of cholestatic rats were reversed by naltrexone treatment.
      These results suggest a possible role for endogenous opioids in inducing
      cholestatic nephrotoxicity.

PMID- 20153757
TI  - Modeling erythropoiesis subject to malaria infection.
AB  - A mathematical model of erythropoiesis subject to malaria infection is developed
      by combining ideas from previous models that addressed only one of the two
      phenomena. The nature of the model allows one to account for suppression of
      erythropoiesis by the toxin hemozoin, which is a by-product of digested
      hemoglobin. Following the derivation of the model, numerical simulations are
      performed and show that the number of parasites produced per bursting erythrocyte
      has the most significant effect of erythropoiesis. It is also shown that removing
      hemozoin may be an effective method for aiding the recovery of the erythrocyte
      population, but is not effective in maintaining a healthy population in the early
      stages of infection. The second half of the paper introduces an implicit finite
      difference scheme that was used to perform the simulations previously mentioned.
      An existence-uniqueness result is then provided via the numerical method.

PMID- 20153758
TI  - Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human
      cells.
AB  - The formation of 8-hydroxyguanine (8-OH-Gua, 7,8-dihydro-8-oxoguanine) in DNA and
      in the nucleotide pool results in G:C-->T:A and A:T-->C:G substitution mutations,
      respectively, due to the ability of 8-OH-Gua to pair with both C and A. In this
      study, shuttle plasmid DNAs containing 8-OH-Gua paired with C and A in the supF
      gene were transfected into human 293T cells, in which specialized DNA polymerases
      were knocked-down. The DNAs replicated in the cells were recovered and then
      introduced into an indicator strain of Escherichia coli. Mutation analysis
      indicated that the knock-downs of DNA polymerases eta and zeta by siRNAs enhanced
      the G:C-->T:A mutations caused by 8-OH-Gua:C. The 8-OH-Gua:C-induced mutation
      frequency was not further increased by double knock-downs of DNA polymerases eta
      and zeta, suggesting that the two DNA polymerases work in the same pathway. In
      addition, the reduction of DNA polymerase eta slightly decreased the A:T-->C:G
      substitutions caused by 8-OH-Gua:A. These results suggest that DNA polymerases
      eta and zeta are involved in the bypass of 8-OH-Gua in human cells.

PMID- 20153759
TI  - Influence of BDNF and COMT polymorphisms on emotional decision making.
AB  - Decision making is an important brain function. Although little is known about
      the genetic basis of decision making, it has been suggested that it is mediated
      by the modulation of neurotransmitter systems. We investigated how the BDNF
      Val66Met and COMT Val158Met polymorphisms affect emotional decision making using
      the Iowa Gambling Task (IGT). One hundred sixty-eight healthy Korean college
      students (93 males, 75 females) with a complete dataset were included in the data
      analysis. The IGT and genotyping for the polymorphisms of BDNF Val66Met and COMT
      Val158Met were performed. Both Met/Met and Val/Met of the BDNF Val66Met
      polymorphism were significantly associated with a lower mean score of blocks 3-5
      of the IGT and with less improvement from block 1 to block 3-5 than the Val/Val.
      However, the BDNF was not significantly associated with the score of block 1, and
      the COMT Val158Met polymorphism produced no significant effect on IGT
      performance. No interaction effect was observed between the BDNF and the COMT for
      the IGT. These findings suggest the BDNF Val66Met may affect the emotional
      decision making performance.

PMID- 20153760
TI  - A mutant thyroid hormone receptor alpha1 alters hippocampal circuitry and reduces
      seizure susceptibility in mice.
AB  - Thyroid hormone deficiency during early developmental stages causes a multitude
      of functional and morphological deficits in the brain. In the present study we
      investigate the effects of a mutated thyroid hormone receptor TR alpha 1 and the
      resulting receptor-mediated hypothyroidism on the development of GABAergic
      neurotransmission and seizure susceptibility of neuronal networks. We show that
      mutant mice have a strong resistance to seizures induced by antagonizing the
      GABA(A) receptor complex. Likewise the hippocampal network of mutant mice shows a
      decreased likelihood to transform physiological into pathological rhythmic
      network activity such as seizure-like interictal waves. As we demonstrate the
      cellular basis for this behavior is formed by the excitatory nature of GABAergic
      neurotransmission in the mutant mice, possibly caused by altered Cl(-)
      homeostasis, and/or the altered patterning of calretinin-positive cells in the
      hippocampal hilus. This study is, to our knowledge, the first to show an effect
      of maternal and early postnatal hypothyroidism via TR alpha 1 on the development
      of GABAergic neurotransmission and susceptibility to epileptic seizures.

PMID- 20153761
TI  - Do our brain hemispheres exchange some stimulus aspects better than others?
AB  - The communication between the two brain hemispheres involves considerable
      information losses. This study investigated whether these losses might be reduced
      for frequently processed stimulus attributes and currently attended stimulus
      properties. It was assumed that size should be more often processed than
      animateness, since estimating object size is essential for motor planning. Thus,
      if the transfer deficits were curbed for frequently processed stimulus aspects,
      then they should be smaller for size than for animateness. By contrast, if the
      transfer losses were reduced for currently attended stimulus features, then they
      should depend on the task: in a size judgement task they should be smaller for
      size, and in an animateness judgement task they should be smaller for
      animateness. To test the interhemispheric transmission of the two stimulus
      properties, a lateralized priming paradigm was implemented, in which one group of
      participants judged targets according to their size and another group according
      to their animateness. It was found that the transfer deficits were virtually
      absent for size, but very pronounced for animateness. Hence, the present data
      provide the first evidence that interhemispheric transmission losses vary for
      particular stimulus features and that they may be reduced with practice. Since
      there was no priming for unattended stimulus properties, it remains open whether
      attention to certain stimulus aspects can improve the interhemispheric exchange
      as well.

PMID- 20153762
TI  - Theory of mind deficits in patients with acquired brain injury: a quantitative
      review.
AB  - Impaired theory of mind (ToM) reasoning is considered an underlying cause of
      social cognition deficits in patients with acquired brain injury (ABI). However,
      the literature does not agree on the severity of ToM impairment in this clinical
      population, nor does it coincide on the proper tools for its assessment. In this
      paper, we use a meta-analytic approach to review 26 studies which compare the
      performance of ABI patients and healthy controls in four widely-used ToM tasks:
      first-order belief task, second order belief task, understanding indirect speech
      (IS) and social faux pas. Overall, patients show moderate to severe ToM
      impairment. The latter appears in faux pas (effect size=0.70) and understanding
      IS tasks (ES=0.87), while moderate impairment can be seen in second-order
      (ES=0.60) and first-order belief tasks (ES=0.52). The severity of ToM impairment
      was influenced by ratio of patients with frontal lobe lesion, ratio of patients
      with right hemisphere injury, type of belief task, and heterogeneity of the
      sample's etiology. Our results provide important quantitative evidence on the
      severity of ToM deficits in the ABI population, while identifying variables that
      influence these deficits. Implications for basic and clinical neuropsychology are
      discussed.

PMID- 20153763
TI  - Conceptual proposition selection and the LIFG: neuropsychological evidence from a
      focal frontal group.
AB  - Much debate surrounds the role of the left inferior frontal gyrus (LIFG).
      Evidence from lesion and neuroimaging studies suggests the LIFG supports a
      selection mechanism used in single word generation. Single case studies of
      dynamic aphasic patients with LIFG damage concur with this and extend the finding
      to selection of sentences at the conceptual preparation stage of language
      generation. A neuropsychological group with unselected focal frontal and non
      frontal lesions is assessed on a sentence generation task that varied the number
      of possible conceptual propositions available for selection. Frontal patients
      with LIFG damage when compared to Frontal patients without LIFG damage and
      Posterior patients were selectively impaired on sentence generation tests only
      when stimuli activated multiple conceptual propositions that compete with each
      other for selection. We found that this selective impairment is critical for
      reduced speech rate, the core deficit of dynamic aphasia, and we would argue it
      is causative for one form of dynamic aphasia associated with LIFG lesions. These
      results provide evidence that the LIFG is crucial for selecting among multiple
      competing conceptual propositions for language generation.

PMID- 20153764
TI  - Coherent motion processing in autism spectrum disorder (ASD): an fMRI study.
AB  - A deficit in global motion processing caused by a specific dysfunction of the
      visual dorsal pathway has been suggested to underlie perceptual abnormalities in
      subjects with autism spectrum disorders (ASD). However, the neural mechanisms
      associated with abnormal motion processing in ASD remain poorly understood. We
      investigated brain responses related to the detection of coherent and random
      motion in 15 male subjects with ASD and 15 age- and IQ-matched healthy controls
      (aged 13-19 years) using event-related functional magnetic resonance imaging
      (fMRI). Behaviorally, no significant group differences were observed between
      subjects with ASD and controls. Neurally, subjects with ASD showed increased
      brain activation in the left primary visual cortex across all conditions compared
      with controls. A significant interaction effect between group and condition was
      observed in the right superior parietal cortex resulting from increased neural
      activity in the coherent compared with the random motion conditions only in the
      control group. In addition, neural activity in area V5 was not differentially
      modulated by specific motion conditions in subjects with ASD. Functional
      connectivity analyses revealed positive correlations between the primary visual
      cortex and area V5 within both hemispheres, but no significant between-group
      differences in functional connectivity patterns along the dorsal stream. The data
      suggest that motion processing in ASD results in deviant activations in both the
      lower and higher processing stages of the dorsal pathway. This might reflect
      differences in the perception of visual stimuli in ASD, which possibly result in
      impaired integration of motion signals.

PMID- 20153765
TI  - Cytotoxic proteins of Amanita virosa Secr. mushroom: purification,
      characteristics and action towards mammalian cells.
AB  - A new hemolytic lectin was purified from the fruit bodies of Amanita virosa Secr.
      mushroom by the affinity chromatography on the cross-linked ovomucin. This lectin
      destroyed erythrocytes of human and animals of various species, and its hemolytic
      activity decreased in the row: rabbit > rat > human > dog. The erythrocytes of
      sheep, cow and carp were resistant to such hemolytic action of the lectin (1
      mg/mL). The lectin-mediated hemolysis was blocked by the polyethylene glycol with
      molecular mass over 1350. A. virosa lectin, unlike Amanita phalloides lectin, did
      not interact with tested monosaccharides. However, the 4-nitrophenyl derivates of
      the monosaccharides inhibited the action of A. virosa lectin which did not prefer
      targeting O-type glycoproteins over the N-type glycoproteins. Murine leukemia
      cells of L1210 line and human leukemia T-cells of CEM T4 and Jurkat lines were
      shown to be sensitive to toxic effect of the lectin and another protein toxovirin
      isolated from A. virosa fruit bodies It was found that toxovirin possessed an
      enzymatic activity of L-amino acid oxidase. Since both toxic proteins--the lectin
      and toxovirin--are sensitive to an elevated temperature, it is suggested that
      they play a significant role in human poisoning only when the unbaked mushroom is
      eaten.

PMID- 20153766
TI  - Effects of aging and gender on muscle mass and regulation of Akt-mTOR-p70s6k
      related signaling in the F344BN rat model.
AB  - Sarcopenia is the loss of muscle mass and strength which occurs with aging.
      Whether the molecular basis of sarcopenia differs with muscle type and across sex
      is not well understood. Here we examine how aging affects the regulation of
      protein kinase B (Akt), the mammalian target of rapamycin (mTOR), AMP activated
      kinase (AMPK), p70 ribosomal S6 kinase (p70s6k), S6 ribosomal protein (rps6) and
      calcineurin (CaN) in the slow soleus and fast extensor digitorum longus (EDL)
      muscles of 6- (adult), 30- (aged), and 36-month (very aged) male and 6- (adult),
      26- (aged), and 30-month (very aged) female Fischer 344xBrown Norway (F344BN)
      rats. In male animals, soleus and EDL muscle to body weight ratios decreased
      steadily with age while in the females, losses remained unchanged after 26
      months. These age-related changes in the degree of muscle atrophy across sex were
      associated with differences in the regulation of Akt, mTOR, and p70s6k in the
      slow-twitch soleus and the regulation of AMPK, 4EBP1, p70s6k and rpS6 in the fast
      twitch EDL. Irrespective of muscle type, aging in both the genders was associated
      with increased calcineurin expression. Taken together, these data suggest that
      indices of protein synthesis and muscle adaptation are regulated differently with
      aging in different muscle types and sex.

PMID- 20153767
TI  - Characterization and antioxidant activity of two low-molecular-weight
      polysaccharides purified from the fruiting bodies of Ganoderma lucidum.
AB  - Two low-molecular-weight polysaccharides, GLP(L)1 and GLP(L)2, purified from a
      crude Ganoderma lucidum polysaccharide preparation GLPP were investigated for
      their physicochemical properties, structure characterization and antioxidant
      activities. The results indicated that GLP(L)1 was a glucan with an average
      molecular weight of 5.2kDa, while GLP(L)2 was composed of glucose, galactose and
      mannose in a ratio of 29:1.8:1.0 with the average molecular weight of 15.4kDa.
      GLP(L)1 and GLP(L)2 had similar structure characteristic which contained linkages
      such as -->3)-Glcp-(1-->, -->4)-Glcp-(1-->, -->6)-Glcp-(1-->, -->3,6)-Glcp-(1-->,
      and -->4,6)-Glcp-(1--> in the percentage ratio of 21.9:20.3:23.7:24.0:3.7 and
      23.0:34.6:7.0:14.1:3.0 in the backbone or branches, respectively. Antioxidant
      results showed that both GLP(L)1 and GLP(L)2 exhibited antioxidant activities
      while GLP(L)1 was more effective in free radicals scavenging and Fe(2+)
      chelating. Low-molecular-weight polysaccharide seems to play an important role in
      the exploration of natural antioxidants in food industry and pharmaceuticals.

PMID- 20153768
TI  - Isolation, gene cloning and expression profile of a pathogen recognition protein:
      a serine proteinase homolog (Sp-SPH) involved in the antibacterial response in
      the crab Scylla paramamosain.
AB  - To identify the frontline defense molecules against microbial infection in the
      crab Scylla paramamosain, a live crab pathogenic microbe, Vibrio
      parahaemolyticus, was recruited as an affinity matrix to isolate innate immune
      factors from crab hemocytes lysate. Interestingly, a serine proteinase homolog
      (Sp-SPH) was obtained together with an antimicrobial peptide
      antilipopolysaccharide factor (Sp-ALF). We then determined the full-length cDNA
      sequence of Sp-SPH, which contained 1298bp with an open reading frame of 1107bp
      encoding 369 amino acid residues. Multiple alignment analysis showed that the
      deduced amino acid sequences of Sp-SPH shared overall identity (83.8%) with those
      of SPH-containing proteins from other crab species. Tissue distribution analysis
      indicated that the Sp-SPH transcripts were present in various tissues including
      eye stalk, subcuticular epidermis, gill, hemocyte, stomach, thorax ganglion,
      brain and muscle of S. paramamosain. The Sp-SPH was highly expressed in selected
      different development stages including embryo (I, II, III and V), zoea (I),
      megalopa, and juvenile. Importantly, the prophenoloxidase was also present in the
      embryos, zoea, juvenile and adult crabs, but relatively lower in megalopa
      compared to those of other stages. Furthermore, the Sp-SPH mRNA expression showed
      a statistically significant increase (P<0.05) in both hemocyte and subcuticular
      epidermis at 24h, and in gill at 96h after challenge of V. parahaemolyticus
      determined by quantitative real-time PCR. Taken together, the live-bacterial
      binding activity and the acute-phase response against bacterial infection of Sp
      SPH suggested that it might function as an innate immune recognition molecule and
      play a key role in host defense against microbe invasion in the crab S.
      paramamosain.

PMID- 20153769
TI  - The neurobiology of repetitive behavior: ...and men.
AB  - In young, typically developing children, repetitive behavior similar to that in
      certain neuropsychiatric syndromes is common. Whereas this behavior is adaptive
      in typical development, in many disorders it forms a core component of symptoms
      and causes prominent impairment in the daily life of affected individuals.
      Understanding the neurobiological mechanisms involved repetitive behavior will
      improve our understanding of the pathogenesis of developmental neuropsychiatric
      disorders, stimulating novel approaches to these conditions. However, studies on
      the neurobiology of human repetitive behavior have often been limited to distinct
      conditions and generalization has been hindered by inconsistent terminology. In
      this paper, we synthesize the 'disorder-driven' literature, building on findings
      from fundamental animal research and translational models. These findings suggest
      a model for classifying repetitive behavior by its neuroanatomical correlates.

PMID- 20153770
TI  - Unselected hepatitis C screening of men who have sex with men attending sexual
      health clinics.
AB  - Sexual transmission of hepatitis C (HCV) between HIV positive men who have sex
      with men (MSM) is increasingly being reported. There is limited and conflicting
      data as to whether HIV negative MSM are at increased risk of infection. Local
      directorate guidelines recommended HCV testing only in MSM having a sexual
      transmitted infection (STI) screen who disclosed risk factors. In 2007 we
      introduced unselected screening into routine practice within our sexual health
      clinics. This report reviews the results of this change in our practice. Over 6
      months, 3365 MSM attended for STI screening. Of 2309 MSM who agreed to be
      screened for HCV (69%) the prevalence of HCV was 0.65% (95% CI 0.36-1.1). This is
      similar to the prevalence of HCV in the general population within England. We
      conclude that unselected screening of MSM for HCV within our sexual health
      services is not currently justified.

PMID- 20153771
TI  - Parvovirus B19 infection associated with Hashimoto's thyroiditis in adults.
AB  - OBJECTIVE: Parvovirus B19 is a common human pathogen, which has been linked to
      autoimmune diseases recently. The aim of the study is to evaluate whether B19 is
      involved in adult Hashimoto's thyroiditis (HT). METHODS: Eighty-six thyroid
      tissues from the adult patients with a spectrum of thyroid disorders were
      examined for B19 DNA and capsid protein by nested PCR, in-situ hybridization and
      immunohistochemistry. The presence of viral DNA in HT epithelium was studied by
      laser-capture microdissection and sequencing of PCR products. The expressions of
      nuclear factor-kappaB (NF-kappaB) and interleukin-6 were investigated by
      immunohistochemistry. RESULTS: B19 DNA was significantly present in HT tissues by
      both PCR (29/32, 90.6%) and in-situ hybridization (23/32, 71.9%, all p < 0.01)
      compared with normal thyroid tissue (7/16, 43.8%; 2/16, 12.5%). Laser-capture
      microdissection further confirmed this difference. B19 capsid protein in HT group
      was significantly higher than that in all the control groups (p < 0.01), and the
      expression of NF-kappaB and interleukin-6 in HT tissues was up-regulated. NF
      kappaB was well co-localized with B19 protein in thyroid epithelia by double
      labeling immunofluorescence and confocal microscopy. CONCLUSIONS: The presence of
      B19 nuclear acid and viral protein was significantly common in HT tissues and it
      suggested a possible role of B19 in adult HT.

PMID- 20153772
TI  - Re: Rapid influenza diagnostic test during the outbreak of the novel influenza
      A/H1N1 2009 in Thailand: an experience with better test performance in resource
      limited setting.

PMID- 20153773
TI  - Empiric albendazole therapy and new onset seizures--a cautionary note.

PMID- 20153774
TI  - Optimizing Drosophila olfactory learning with a semi-automated training device.
AB  - Drosophila olfactory aversive conditioning has served as a powerful model system
      with which to elucidate the molecular and neuronal mechanisms underlying memory
      formation. In the typical protocol, flies are exposed to a constant odor stream
      while receiving a pulsed electric shock in the conditioning tube of a manual
      apparatus. We have devised a simple, low-cost semi-automated conditioning
      apparatus that computationally controls the delivery of odor and shock. A
      semiconductor-based odor sensor is employed to monitor the change of odor
      concentration in the training tube. The system thus allows electric shocks to be
      precisely matched with odor concentration in the training tube. We found that
      short-term memory performance was improved with a pulsed odor flow protocol, in
      which odor is presented in short pulses, each paired with electric shock, rather
      than as a constant flow. The effect of pulsed odor flow might be ascribed to the
      phenomenon of 'conditioned approach', where approach toward an odor is induced
      when the electric shock is presented before odor pulse ends. Our data shows that
      the system is applicable to the study of olfactory memory formation and to the
      examination of conditioning parameters at a level of detail not practical with a
      manual apparatus.

PMID- 20153775
TI  - In vitro antiviral activity of some uridine derivatives of 2-deoxy sugars against
      classical swine fever virus.
AB  - Classical swine fever virus glycoproteins: E2, E(rns) (E0) and E1 are detected on
      the external part of viral particles and play a major role in the initial stages
      of viral infection. They form heterodimeric and homodimeric complexes needed to
      effectively infect host cells. Some glycosylation inhibitors, such as
      tunicamycin, which act at the early stages of glycan chain processing, can
      influence, not only glycosylation, but also the stability of E2 and E(rns)
      glycoproteins, effectively inhibiting the formation of glycoprotein complexes and
      virus yield. In our study we tested two of newly designed uridine derivatives of
      2-deoxy sugars, IW3 and IW7 mimicking part of tunicamycin. We showed that
      inhibitors effectively arrest viral growth with IC(50) of 9 and 7microg/ml
      respectively, without significant toxicity for mammalian cells. Moreover, IW3 and
      IW7 reduced the formation of viral glycoproteins E2 and E(rns) in a dose
      dependent manner. These compounds were further studied in order to elucidate the
      molecular mechanism of the antiviral effect using mammalian SK6 and insect Sf9
      cell lines. We found that they inhibit N-glycosylation process of viral proteins
      at the late stage of glycan modification characteristic for mammalian cells. Due
      to the observed antiviral effect accompanied by low cytotoxicity, these
      inhibitors are potential candidates for anti-pestivirus therapy.

PMID- 20153776
TI  - Reverse micelle-encapsulated recombinant baculovirus as an oral vaccine against
      H5N1 infection in mice.
AB  - Induction of mucosal immunity through oral immunization is an effective way to
      control influenza infection. In this study, baculovirus displaying influenza
      hemagglutinin was encapsulated within a reverse micelle structure of
      phosphatidylcholine and delivered into the gastrointestinal tract of mice to
      study its efficacy as an oral vaccine against cross-clade H5N1 infection. Mice
      vaccinated with encapsulated baculovirus displaying HA (En-BacHA) showed
      significantly enhanced HA specific serum IgG and mucosal IgA antibodies, and
      higher hemagglutination inhibition (HI) titers, when compared to its non
      encapsulated form (BacHA). Estimation of serum neutralizing antibodies also
      indicated that En-BacHA formulation was able to induce strong cross-clade
      neutralization against heterologous H5N1 strains (clade 1.0, clade 2.1, clade 4.0
      and clade 8.0). Further, mice vaccinated with En-BacHA alone were able to confer
      100% protection against 5MLD50 of HPAI heterologous H5N1 strain (clade 1).
      Inclusion of recombinant cholera toxin B subunit as a mucosal adjuvant in the
      vaccine formulation did not show any significant effect in both systemic and
      mucosal immune responses. Oral delivery of encapsulated recombinant H5 HA
      expressed on baculovirus surface is an effective way to prime the immune system
      against H5N1 infection in mice and will have no biosafety concerns associated
      with their production or administration.

PMID- 20153777
TI  - A high-throughput assay using dengue-1 virus-like particles for drug discovery.
AB  - Dengue virus (DENV) is a mosquito-borne flavivirus responsible for 50-100 million
      human infections each year. The development of DENV chemotherapy requires high
      throughput screening (HTS) assays. A dengue virus-like particle (VLP) has been
      constructed using viral structural proteins to package a Renilla luciferase
      reporter replicon. VLP could be produced by either the sequential electroporation
      of the replicon RNAs and the structural gene RNAs or by electroporating replicon
      RNA into a stable cell line expressing the structural proteins. In both
      approaches, the key to produce high titer VLP (3x10(6)foci-forming unit/ml) is to
      use low temperature (30 degrees C) in the packaging step. In addition, exogenous
      expression of host protease furin increased VLP infectivity. The infection could
      be blocked by antibodies against viral envelope protein and by an inhibitor of
      viral NS5 polymerase, but not by an inhibitor of host alpha-glucosidase
      (castanospermine). The VLP infection assay was optimized for HTS in a 384-well
      format with consistent and robust signal, providing a simple and rapid cell-based
      assay for screening inhibitors against DENV entry, translation, and replication
      in an HTS format.

PMID- 20153778
TI  - Peripheral and cerebral metabolic abnormalities of the tryptophan-kynurenine
      pathway in a murine model of major depression.
AB  - Occurring both peripherally and centrally, the kynurenine pathway (KP) - an
      alternative pathway to 5-HT synthesis from tryptophan (TRP) - could be of
      particular value to better understand the link between peripheral changes of
      circulating levels of glucocorticoids (GC)/proinflammatory cytokines and altered
      neurotransmission observed in depressed patients. Indeed, it is activated by
      these mediators of stress and can produce several neuroactive compounds like
      quinolinic acid (QUIN) and kynurenic acid (KYNA) that can respectively increase
      and decrease glutamate concentration in brain. In order to characterize the role
      of both the peripheral and cerebral KP in the pathophysiology of depressive
      disorders, we used the Unpredictable Chronic Mild Stress (UCMS) to induce a
      depressive-like syndrome and we then measured the level of relevant TRP-KYN
      pathway metabolites: KYN, 3-hydroxykynurenine (3HK; precursor of QUIN) and KYNA.
      We also measured TRP-5HT pathway metabolites: TRP, 5-HT, 5-HIAA. We showed that
      UCMS increased TRP catabolism along the KP in the periphery. 5-HT and KYN were
      found to be strongly negatively correlated in all brain structures of control
      mice and of UCMS mice except in the hippocampus. More importantly we found that
      KYN was preferentially metabolized along the QUIN pathway at the subcortical
      level (amygdala/striatum) whereas, at the cortical level (cingulate cortex), the
      QUIN pathway was reduced. Considering the role of these metabolites on the
      glutamatergic neurotransmission, we propose that such KP alterations could
      participate to the cortical/subcortical glutamatergic alterations reported in
      depressed patients.

PMID- 20153779
TI  - Spatial memory deficits and thalamic serotonergic metabolite change in thiamine
      deficient rats.
AB  - The purposes of the present study were to verify the effects of a severe thiamine
      deficiency episode on spatial cognitive aspects and thalamic serotonergic
      parameters. The animals were submitted to a severe thiamine deficiency treatment
      that was interrupted after the onset of the last neurological signs. The results
      obtained confirm previous findings about TD deficiency effects on cognitive
      function and, further show that this vitamin increases the thalamic serotonine
      metabolite, 5-hidroxyindolacetic acid (5-HIAA), level. In addition, the present
      data shed light on the importance of this metabolite in spatial cognitive
      function.

PMID- 20153780
TI  - Locomotion analysis of Sprague-Dawley rats before and after injecting 6-OHDA.
AB  - The hypothesis that changes in measured ground reaction forces and time
      parameters during locomotion can noninvasively detect Parkinsonism in unilateral
      6-OH dopamine (6-OHDA) lesioned rats is tested. It was found that changes of
      seven locomotion parameters can be used to construct a logistic regression model
      with a detection sensitivity and specificity of over 90% as compared to non
      lesioned rats. Comparisons between this model and other neurological and
      neuromuscular disorders are presented.

PMID- 20153781
TI  - Selective lesions of the dorsomedial striatum impair serial spatial reversal
      learning in rats.
AB  - Impairments in reversal learning have been attributed to orbitofrontal cortex
      (OFC) dysfunction in many species. However, the role of subcortical areas
      interconnected with the OFC such as the striatum remains poorly understood. This
      study directly evaluated the contribution of core and shell sub-regions of the
      nucleus accumbens (NAc), dorsomedial (DMS) and dorsolateral (DLS) striatum to
      reversal learning of an instrumental two-lever spatial discrimination task in
      rats. Selective NAc core, DMS and DLS lesions were achieved with microinjections
      of quinolinic acid and NAc shell lesions with ibotenic acid. Damage to NAc core
      or shell did not affect retention of a previously acquired instrumental spatial
      discrimination. In contrast, DLS and DMS lesions produced changes in aspects of
      discrimination performance such as the latency to collect earned food pellets.
      Neither NAc core or shell lesions nor DLS lesions affected the main indices of
      reversal performance. Conversely, DMS lesion rats showed a significant impairment
      in reversal learning. DMS damage increased the number of errors to reach criteria
      that were perseverative in nature. The deficit in reversal learning in DMS lesion
      rats was not associated with an impairment to extinguish instrumental responding.
      There were no effects on spontaneous locomotor activity. Our data are in
      agreement with recent work showing that lesions of the medial striatum in
      marmoset monkeys produce perseverative impairments during a serial visual
      discrimination reversal task and support the hypothesis that dorsomedial striatal
      dysfunction contributes to pathological perseveration, which is a common feature
      of many psychiatric disorders.

PMID- 20153783
TI  - Participation of extracellular Ca(2+) or ghrelin in peptide-mediated contraction
      of strips from rat urinary bladder.
AB  - Many neuropeptides, like angiotensins and vasopressin, are involved in the
      regulation of urinary bladder contractile activity. They activate the inositol
      triphosphate signal pathway and increase intracellular calcium concentration. To
      determine the effect of ghrelin and extracellular calcium on the amplitude and
      force of angiotensin and vasopressin-mediated contractions of detrusor, we used
      strips from urinary bladder of Wistar rats. The obtained preparations were
      stimulated with Angiotensin II (Ang II) and arginine-vasopressin (AVP),
      independently and in combination with CaCl(2) or ghrelin. The simultaneous
      application of peptide and CaCl(2) increased the amplitude and the integral force
      (AUC) of muscle contraction for both neuropeptides. If ghrelin was applied to the
      preparation 30min prior to application of Ang II, it prevented the development of
      typical Ang II-mediated contraction. Ghrelin did not affect the amplitude of AVP
      mediated contraction, but significantly lowered its integral force. Our
      experimental data indicate that the increase of calcium in the extracellular
      fluid possesses a synergistic effect on the neuropeptide-mediated contraction.
      The effects of ghrelin on Ang II- and AVP-mediated contractions allow us to
      express the assumption that the urinary bladder cells probably have ghrelin
      receptors which do not activate phospholipase C signal pathway.

PMID- 20153784
TI  - A conserved function for Inp2 in peroxisome inheritance.
AB  - In budding yeast Saccharomyces cerevisiae, the peroxisomal protein Inp2 is
      required for inheritance of peroxisomes to the bud, by connecting the organelles
      to the motor protein Myo2 and the actin cytoskeleton. Recent data suggested that
      the function of Inp2 may not be conserved in other yeast species. Using in silico
      analyses we have identified a weakly conserved Inp2-related protein in 18 species
      of budding yeast and analyzed the role of the identified protein in the
      methylotrophic yeast Hansenula polymorpha in peroxisome inheritance. Our data
      show that H. polymorpha Inp2 locates to peroxisomes, interacts with Myo2, and is
      essential for peroxisome inheritance.

PMID- 20153785
TI  - Traces of fear in the neural web--magnetoencephalographic responding to arousing
      pictorial stimuli.
AB  - The concept of a 'fear network', i.e. an interconnected set of neural
      representations has been instrumental in explaining symptoms and their
      maintenance in anxiety disorders. The neural representations include both,
      response propositions such as flight or freezing and chunks of memory,
      conceptualized as Hebbian cell assemblies. Consequently, the fear network
      undergoes neuroplastic modifications, for instance, incremental enlargements with
      repeated exposure to threat and danger. This will in turn modify future
      processing of sensory stimuli and ultimately lead to an altered architecture of
      the brain's processing machinery and information processing modes. Using repeated
      exposure to traumatic stress as a model to study these processes, we summarize a
      series of magnetoencephalographic investigations from our laboratory, which
      demonstrate a characteristic pattern of early activation (before 100 ms latency
      to the eliciting stimulus) in fronto-cortical circuits by high-arousing, aversive
      pictorial and verbal stimuli in individuals presenting with posttraumatic stress
      disorder (PTSD). We propose that this pattern reflects a preference of stressed
      brains to engage a 'low road' sensory processing, which is fast but uncoupled
      from prefrontal regulatory control and which easily activates an alarm response,
      whereas less emphasis is given the more careful and contextual processing via the
      'high road' along the ventral stream. As a result, the brain's architecture is
      changed from a careful analyzer of the environment to a rapid threat detector
      with a low threshold to engage in costly defense.

PMID- 20153782
TI  - Effects of eszopiclone and zolpidem on sleep-wake behavior, anxiety-like behavior
      and contextual memory in rats.
AB  - At present, eszopiclone and zolpidem are the most commonly prescribed drugs for
      treating insomnia. Despite the established relationship between sleep disturbance
      and anxiety, it remains unknown whether targeted treatment for insomnia may
      affect acute anxiety. Therefore, the objective of this study was to examine the
      effects of three different doses (1, 3, and 10mg/kg) of eszopiclone and zolpidem
      on the states of sleep and wakefulness, levels of anxiety-like behavior, and long
      term contextual memory in footshock-induced anxious rats. The results of this
      study demonstrated that the administration of eszopiclone and zolpidem both were
      equally effective in attenuating footshock stressor-induced suppression of slow
      wave sleep (SWS). The administration of eszopiclone at 1mg/kg or zolpidem at 1
      and 3mg/kg doses showed a tendency for attenuating stressor-induced suppression
      of REM sleep. However, the REM sleep attenuating effects of these drugs
      disappeared when they were administered at higher doses. The administration of
      eszopiclone at 3 and 10mg/kg doses and zolpidem at all three doses reduced the
      power of electroencephalographic theta band frequencies during wakefulness. In
      addition, the administration of eszopiclone at 1 and 3mg/kg doses suppressed
      stressor-induced anxiety-like behavior. The administration of zolpidem at 1, 3,
      or 10mg/kg doses was not effective in attenuating stressor-induced anxiety-like
      behavior. Contextual memory after administration of eszopiclone at 1mg/kg dose
      had no effects, but was reduced significantly with increased dosage. Contextual
      memory after administration of zolpidem, at all three doses, was severely
      disrupted. The results of this study suggest that eszopiclone at a low dose could
      be used effectively to control anxiety and anxiety-induced insomnia.

PMID- 20153786
TI  - Aesthetic judgments of music in experts and laypersons--an ERP study.
AB  - We investigated whether music experts and laypersons differ with regard to
      aesthetic evaluation of musical sequences. 16 music experts and 16 music
      laypersons judged the aesthetic value (beauty judgment task) as well as the
      harmonic correctness (correctness judgment task) of chord sequences. The
      sequences consisted of five chords with the final chord sounding congruous,
      ambiguous or incongruous relative to the harmonic context established by the
      preceding four chords. On behavioural measures, few differences were observed
      between experts and laypersons. However, several differences in event-related
      potential (ERP) parameters were observed in auditory, cognitive and aesthetic
      processing of chord cadences between experts and laypersons. First, established
      ERP effects known to reflect the processing of harmonic rule violation were
      investigated. Here, differences between the groups were observed in the
      processing of the mild violation - experts and laypersons differed in their early
      brain responses to the beginning of the chord sequence. Furthermore, ERP data
      indicated distinctions between experts and laypersons in aesthetic evaluation at
      three different stages. Firstly, during the interval of task-cue presentation, a
      stronger contingent negative variation (CNV) to the beauty judgment task was
      observed for experts, indicating that experts invest more effort into preparation
      for aesthetic processes than into correctness judgments. Secondly, during the
      first four chords, preparation for the correctness judgment required more
      exertion on the laypersons' side. Thirdly, during the last chord, laypersons
      showed a larger late and widespread positivity for the beauty compared to the
      correctness judgment, indicating a stronger reliance on internal affective states
      while forming a judgment.

PMID- 20153787
TI  - Prolongation and enhancement of the anti-apoptotic effects of PTD-Hsp27 fusion
      proteins using an injectable thermo-reversible gel in a rat myocardial infarction
      model.
AB  - Ischemic heart disease has emerged as a leading cause of death worldwide.
      Conventional surgery-based therapy for this disease, especially myocardial
      infarction, requires additional pharmaceutical agents using heart's endogenous
      protective mechanism to suppress the progress and recurrence of the disease. Heat
      shock protein 27 (Hsp27) has been considered to be a potentially therapeutic
      protein for the treatment of ischemic heart disease due to its anti-apoptotic and
      protective effects on cardiomyocytes under stressful conditions. Despite the
      potency of Hsp27, low transduction efficiency, protein instability, and a short
      half-life in the body have limited its in vivo applications. Protein transduction
      domains (PTD) were recombinantly fused with Hsp27 to enhance transduction
      efficiency. Although the intracellular delivery of the PTD-Hsp27 fusion proteins
      was significantly enhanced compared with Hsp27, the instability and short half
      life of the PTD-Hsp27 fusion proteins still need to be improved for in vivo
      applications. Injectable thermo-reversible gel system was developed and found to
      be effective in stabilizing and retarding the release of the PTD-Hsp27 fusion
      proteins both in vitro and in vivo. PTD-Hsp27-loaded thermo-reversible gels were
      locally administered to the heart muscle in a ligation/reperfused rat myocardial
      infarction model and the long-term therapeutic efficacy was observed by measuring
      the inhibition of apoptosis and the area of fibrosis.

PMID- 20153788
TI  - Transungual iontophoresis of lithium and sodium: effect of pH and co-ion
      competition on cationic transport numbers.
AB  - Iontophoresis has been proposed as an alternative method to deliver drugs into
      and across the nail plate. However, the knowledge about the rules governing
      transungual iontophoretic transport numbers is still uncomplete. This work
      investigated the iontophoretic and passive transungual fluxes of sodium and
      lithium and the effect of pH and co-ion competition on the cations' transport
      numbers. The objective was to further investigate whether nails show cation
      permselectivity at physiological pH and to improve our understanding of transport
      numbers during transungual iontophoresis. The donor solutions comprised the
      single ion and binary mixtures of the two cations at different pH. Sodium and
      lithium iontophoretic fluxes showed low inter-nail variability and were
      significantly greater than passive fluxes. Cationic transport numbers clearly
      increased as the pH was sequentially raised from 4.0 to 5.0 and then to 7.0, in
      agreement with a net negative charge of the human nails at physiological pH.
      Sodium transport number was maximal when the ion was formulated as a single ion
      (absence of competing co-ions) and decreased as the molar fraction of lithium was
      increased in the vehicle. The magnitude of the transport numbers measured and
      their response to changes in the cations' molar fraction and pH in the donor
      solution were remarkably similar to those observed during the transdermal
      iontophoresis. The ratio of lithium and sodium transport numbers was directly
      proportional to their relative concentration ratios; the proportionality constant
      being remarkably similar in the 4.0-7.0 pH range as well as to the ratio of the
      cations' aqueous mobilities. Another interesting similarity with transdermal
      iontophoresis was the existence of a cationic transport number threshold. On the
      whole, this work provided some key information about nail permselectivity and
      transungual transport numbers which will assist to formulate efficiently
      therapeutic compounds to be delivered iontophoretically into and across the nail
      plate.

PMID- 20153789
TI  - Multicomponent chemical enhancer formulations for transdermal drug delivery: more
      is not always better.
AB  - Chemical permeation enhancers can permeabilize the human skin to enable
      transdermal delivery of drugs, but their use is often limited by the accompanying
      skin irritation. Novel chemical enhancer combinations based on synergistic
      interactions amongst their components have the potential to address this
      limitation. However, discovery of such combinations requires screening of large
      libraries of chemicals and the size of such libraries increases exponentially
      with the number of ingredients in the formulation. Therefore, it becomes
      important to develop heuristic rules for optimizing such libraries, especially at
      higher orders. In the present study, a formulation library containing binary,
      ternary and quaternary combinations was designed using a common pool of 10
      chemical enhancers and was screened for skin permeation enhancement. The key
      question was whether increasing the number of ingredients in the formulation
      yields increased permeation enhancement. Formulation potencies and synergies were
      analyzed to elucidate the role played by the formulation order. Ternary
      formulations exhibited the best cost to benefit ratio as judged by the fraction
      of total formulations that provide high potency.

PMID- 20153790
TI  - Th1 (CXCL10) and Th2 (CCL2) chemokine expression in patients with immune
      thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an acquired organ-specific autoimmune disease
      with a polarization of T(h)1. Both the T(h)1 chemokine CXCL10 and T(h)2 chemokine
      CCL2 have been studied in several autoimmune diseases, but the status of these
      chemokines in ITP is still unknown. The aims of this study were to determine the
      expression of CXCL10 and CCL2 and their receptors, CXCR3 and CCR2, in ITP
      patients, and to conduct a preliminary study of the pathogenic roles of these
      factors in ITP. Plasma samples from 49 patients with ITP and 24 normal healthy
      subjects were assayed for CXCL10 and CCL2 plasma concentration by enzyme-linked
      immunosorbent assay. Real-time quantitative polymerase chain reaction was
      performed to determine the mRNA expression of these chemokines and their
      receptors in the PBMNC of 24 normal controls and 28 active ITP patients as well
      as splenocytes of nine ITP patients. The CXCL10 levels in the plasma samples from
      patients with active ITP were significantly higher than those from healthy
      controls (p = 0.007) and decreased to normal levels in patients with remission
      ITP. In contrast, CCL2 levels were similar in patients with active disease,
      patients in remission, and control subjects. PBMNC of patients with active
      disease expressed more CXCL10 mRNA (p = 0.031) but less CCR2 mRNA (p = 0.005).
      Lower peripheral platelet count correlated with higher CXCL10 levels and
      CXCL10/CCL2 ratios. Our study demonstrated that plasma levels of CXCL10 and
      CXC10/CCL2 ratio were higher in patients with active ITP than in healthy donors,
      and had an association with platelet counts of the patients. CXCL10 might be a
      pathogenic factor of this disorder.

PMID- 20153791
TI  - STAT4 gene influences genetic predisposition to ulcerative colitis but not
      Crohn's disease in the Spanish population: a replication study.
AB  - Recently, the signal transducer and activator of transcription 4 (STAT4) gene has
      been associated with multiple autoimmune diseases. Interestingly, a recent work
      showed that the T allele of the rs7574865 STAT4 SNP was associated with
      inflammatory bowel disease (IBD) in a Spanish population. The aim of the present
      study was to reevaluate the role of the STAT4 rs7574865 polymorphism on IBD. The
      present case-control study included 498 Crohn's disease (CD) patients, 402
      ulcerative colitis (UC) patients, and 1296 healthy matched controls. Genotyping
      was performed using a PCR system with a pre-developed TaqMan allelic
      discrimination assay for the rs7574865 STAT4 SNP. Moreover, a meta-analysis was
      performed with the previous work in a Spanish population and the current study,
      including a final sample size of 1574 IBD patients (820 with CD and 754 with UC)
      and 2012 healthy controls. No evidence of association was found for the current
      case-control study (CD: p = 0.23, OR = 0.9, 95% CI = 0.75-1.1; UC: p = 0.17, OR =
      1.14, 95% CI = 0.95-1.38). However, the meta-analysis showed that the STAT4
      rs7574865 T allele was significantly associated with susceptibility to UC (p =
      0.012 pooled; OR = 1.20, 95% CI = 1.04-1.39) but not CD (p = 0.71 pooled; OR =
      0.93, 95% CI = 0.65-1.34). Our data suggest that the rs7574865 STAT4 SNP is a
      genetic susceptibility variant for UC but not CD in the Spanish population.

PMID- 20153792
TI  - Evaluation of hepatic changes and local and systemic immune responses in goats
      immunized with recombinant Peroxiredoxin (Prx) and challenged with Fasciola
      hepatica.
AB  - Protection against Fasciola hepatica in goats immunized with Peroxiredoxin (Prx)
      was assessed. The experimental trial consisted of three groups of seven animals;
      group 1 were unimmunized and uninfected, group 2 were immunized with adjuvant
      only and group 3 were immunized with recombinant Prx in adjuvant (immunized and
      infected). Immunization with Prx in Quil A adjuvant, group 3, induced a reduction
      in fluke burden of 33.04% when compared to adjuvant control, group 2, although
      this difference was not significant. The hepatic gross and microscopical
      morphometric study revealed lower damage in the Prx-immunized compared to group 2
      (p<0.05). Furthermore, immunohistochemical studies revealed that the Prx
      immunized group exhibited reduced infiltration of CD4(+), CD8(+), IFN-gamma(+)
      and TCR(+) (p<0.05); and CD2(+) and IL-4(+) (p<0.001) in hepatic lesions. Levels
      of anti-Prx serum IgG in group 3 showed a significant increase at the 4th week
      after challenge infection compared with group 2 (p<0.0001). This is the first
      report of ruminant immunization with recombinant Prx of F. hepatica. The study
      shows that this vaccine significantly reduces hepatic damage and encourages
      further studies to improve the vaccine efficacy.

PMID- 20153793
TI  - Improved anamnestic response among adolescents boosted with a higher dose of the
      hepatitis B vaccine.
AB  - Some hepatitis B vaccine booster studies have suggested waning of vaccine-induced
      immunity in adolescents vaccinated starting at birth. Those studies, however,
      used a pediatric formulation of the hepatitis B vaccine as a booster to detect
      anamnestic response. We compared adolescents boosted with an adult dose of
      hepatitis B vaccine with those boosted with a pediatric dose. Among adolescents
      who had lost protective antibody levels against hepatitis B, a higher proportion
      had an anamnestic response when boosted with the adult dose (60.0% vs. 43.8%).
      Thus, higher antigen concentrations may be required to elicit an adequate immune
      memory response. Despite improved anamnestic response, our study still raises
      concerns about whether children immunized in early infancy will remain protected
      from hepatitis B as they age into adulthood.

PMID- 20153794
TI  - A whole genome transcriptional analysis of the early immune response induced by
      live attenuated and inactivated influenza vaccines in young children.
AB  - The protective mechanisms of influenza vaccines in young children are not
      completely understood. A phase 2 clinical study was conducted in 85 children 12
      35 months of age to describe and compare the immune responses to live attenuated
      influenza vaccine (LAIV) with trivalent inactivated influenza vaccine (TIV). To
      better understand the biology of vaccine effects, oligonucleotide microarrays
      were employed to measure the genome-wide changes in transcript profiles in whole
      blood at approximately 7 days after 1 dose of LAIV or TIV. Of the total 265
      differentially expressed genes identified in this study, 6 clusters of genes were
      identified to be tightly coexpressed, many of which are likely modulated by
      cytokines including type 1 interferons (IFNs) and granulocyte-macrophage colony
      stimulating factor. Additional functional analyses revealed that the type 1 IFN
      pathway and cell cycle regulation-related genes are enriched in the 6 coexpressed
      gene sets. Promoter characterization of these coexpressed genes also supported
      this conclusion. Moreover, it is suggested that the IFN-stimulated response
      element is likely to be a potential bidirectional promoter, and the
      CCAAT/enhancer-binding protein might cooperate with the E2F transcription factor
      family in the regulation of the cell cycle in the early immune response induced
      by the influenza vaccine. Overall, our study clearly indicates that the
      expression profile changes induced by LAIV are significantly different from those
      induced by TIV. These results suggest that the pattern of overexpression of type
      1 IFN-stimulated genes can potentially be used as a biomarker to identify the
      early vaccination response of LAIV and may also explain, to a certain extent,
      previous clinical study observations of LAIV-induced protection against influenza
      like illness in the first 2 weeks after administration.

PMID- 20153795
TI  - Enhancing therapy of B16F10 melanoma efficacy through tumor vaccine expressing
      GPI-anchored IL-21 and secreting GM-CSF in mouse model.
AB  - In the present study, we developed the tumor vaccine expressing IL-21 in the GPI
      anchored form together with secreting GM-CSFs and investigated its antitumor
      efficacy in C57BL/6 mouse model. The fusion genes containing IL-21 and the GPI
      anchor signal sequence were acquired by overlaping PCR, inserted into the
      downstream of two multi-clone sites in recombinant plasmid pRSC/GM-CSFs to form
      pRSC/IL-21-gpi-GM-CSFs that was transfected into the B16F10 cells. The tumor cell
      vaccine B16F10/IL-21-gpi-GM-CSFs was identified by reverse transcription PCR, IFA
      and FCM, respectively. The results showed that the pRSC/IL-21-gpi-GM-CSFs had no
      cell cycle and proliferative state impact on the B16F10 cells after transfected,
      and that the tumor vaccine B16F10/IL-21-gpi-GM-CSFs increased the cytotoxicities
      of NK cells and CD8(+)CTL, enhanced the level of serum IFN-gamma, augmented
      therapy of tumor effect and prolonged survival time in the tumor-bearing mice
      immunized with the tumor vaccine B16F10/IL-21-gpi-GM-CSFs. The data that we
      presented here provided a rationale and practical platform for clinical testing
      of enhancing cell therapy of B16F10 melanoma efficacy by modified tumor vaccine
      expressing GPI-anchored IL-21 and secreting GM-CSF.

PMID- 20153796
TI  - A comparison of the use of economics in vaccine expert reviews.
AB  - We reviewed how health economics has been included in the vaccine expert review
      processes in a sample of countries. We identified two kinds of review processes -
      those in which vaccines and drugs are assessed using a common process, and those
      in which vaccines are assessed within the infectious disease framework. In either
      process, the countries recommend that their national pharmaco-economic (i.e.,
      guidelines developed for drugs) guidelines be used to conduct the studies,
      although the guidelines themselves differ between countries. As a result of these
      factors, the decision process and the study outcomes can differ between
      countries, but because the vaccine adoption process includes other criteria as
      well, economic factors will not necessarily alter the outcome.

PMID- 20153797
TI  - The secretome of a recombinant BCG substrain reveals differences in hypothetical
      proteins.
AB  - Tuberculosis remains a major human health problem worldwide, and strategies for
      its prevention include the generation and characterization of new recombinant
      vaccines containing immunodominant antigens from Mycobacterium tuberculosis. By
      comparing the secretomes of wild-type Mycobacterium bovis and a PstS1-recombinant
      M. bovis BCG vaccine substrain (rBCG38), we identified six conserved hypothetical
      proteins (BCG2696, BCG1674, BCG0372, BCG0427, BCG2436c, and BCG3053) that are
      differentially expressed. Our findings will aid in the identification of highly
      immunogenic proteins present in rBCG.

PMID- 20153798
TI  - Adverse health effects of anabolic-androgenic steroids.
AB  - Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone.
      Illegally, these drugs are regularly self-administered by body builders and power
      lifters to enhance their sportive performance. Adverse side effects of AAS
      include sexual dysfunction, alterations of the cardiovascular system, psyche and
      behavior, and liver toxicity. However, severe side effects appear only following
      prolonged use of AAS at high dose and their occurrence is limited. Occasionally,
      AAS abuse may be linked to certain social and psychological traits of the user,
      like low self-esteem, low self-confidence, suffered hostility, childhood conduct
      disorder, and tendency to high-risk behavior. The overwhelming stereotype about
      AAS is that these compounds cause aggressive behavior in males. However, the
      underlying personality traits of a specific subgroup of the AAS abusers, who show
      aggression and hostility, may be relevant, as well. Use of AAS in combination
      with alcohol largely increases the risk of violence and aggression. The
      dependence liability of AAS is very low, and withdrawal effects are relatively
      mild. Based on the scores for acute and chronic adverse health effects, the
      prevalence of use, social harm and criminality, AAS were ranked among 19 illicit
      drugs as a group of drugs with a relatively low harm.

PMID- 20153799
TI  - Changes in hippocampal connexin 36 mRNA and protein levels during epileptogenesis
      in the kindling model of epilepsy.
AB  - OBJECTIVE: Identification of key molecular changes occurring during
      epileptogenesis provides better understanding of epilepsy and helps to develop
      strategies to modify those changes and thus, block the epileptogenic process. Gap
      junctional communication is thought to be involved in epileptogenesis. This
      communication can be affected by changes in expression of gap junctional protein
      subunits called connexins (Cxs). One of the main brain regions involved in
      epileptogenesis is the hippocampus in which there is a network of gap junctional
      communication between different cell types. METHOD: Cx36 and Cx43 expressions at
      both mRNA and protein level were measured in rat hippocampus during
      epileptogenesis in the kindling model of epilepsy. RESULTS: Cx36 expression at
      both mRNA and protein level was upregulated during acquisition of focal seizures
      but returned to basal level after acquisition of secondarily-generalized
      seizures. No change in Cx43 gene and protein expression was found during kindling
      epileptogenesis. CONCLUSION: These results further point out the significance of
      Cx36 as a target to modify epileptogenic process and to develop antiepileptogenic
      treatments.

PMID- 20153800
TI  - Extracellular phospholipases in atherosclerosis.
AB  - Phospholipases A2 (PLA2) are a family of enzymes that catalyze the hydrolysis of
      the sn-2 ester bond of glycerophospholipids liberating lysophospholipids and free
      fatty acids; important second messengers involved in atherogenesis. Plasma PAF
      acetylhydrolase (PAF-AH) or Lp-PLA2 is a Ca(2+)-independent PLA2 which is
      produced by monocyte-derived macrophages and by activated platelets, and
      circulates in plasma associated with lipoproteins. PAF-AH catalyzes the removal
      of the acetyl/short acyl group at the sn-2 position of PAF and oxidized
      phospholipids produced during inflammation and oxidative stress. In humans, PAF
      AH is mainly associated with small dense LDL and to a lesser extent with HDL and
      with lipoprotein(a). PAF-AH is N-glycosylated prior to secretion which diminishes
      its association with HDL raising the question of its distribution between the
      proatherogenic LDL vs the antiatherogenic HDL. Hypercholesterolemic patients have
      higher plasma PAF-AH activity which is reduced upon hypolipidemic therapy. PAF-AH
      specific inhibitor darapladib stabilizes human and swine plaques, therefore
      challenging the antiatherogenic potential of PAF-AH shown in small animal models.
      Among secreted PLA2s (sPLA2), the group X sPLA2 (PLA2GX), due to its very high
      activity towards phosphatidylcholine the main phospholipid of LDL, became an
      attractive target in atherosclerosis. We showed that PLA2GX is present in human
      atherosclerotic lesions and that the PLA2GX-phospholipolysed LDL triggers human
      macrophage-foam cell formation. In contrast to other sPLA2s, including group IB,
      IIA and V, PLA2GX can efficiently hydrolyze PAF present in lipoproteins or
      vesicles indicating that PLA2GX may be a novel player in PAF regulation upon
      inflammatory processes. By a genetic approach we uncovered a relatively rare
      polymorphism (Arg38Cys) which produces a catalytically inactive PLA2GX; although
      no association was observed with cardiovascular risk factors in the AtheroGene
      study, this result should be replicated in cohorts of other inflammatory
      diseases. We anticipate that mores studies will be necessary to sort out the
      exact role of extracellular PLA2 family members in atherosclerosis initiation and
      progression.

PMID- 20153801
TI  - Novel families of antimicrobial peptides with multiple functions from skin of
      Xizang plateau frog, Nanorana parkeri.
AB  - Xizang plateau frog (Nanorana parkeri) captured in Lhasa, Tibet, China, solely
      lives in the subtropical plateau, where there is strong ultraviolet radiation and
      long duration of sunshine. Considering its harsh living environment, the frog's
      innate defense against microbes and environmental stress was investigated. In
      current study, three antimicrobial peptides (AMPs) were purified and
      characterized from the skin secretion of N. parkeri. The coding cDNA sequences
      were also cloned from the skin cDNA library of N. parkeri. By structural
      characterization, two peptides were identified belonging to Japonicin-1 family,
      and named as Japonicin-1Npa (FLLFPLMCKIQGKC) and Japonicin-1Npb (FVLPLVMCKILRKC).
      The third peptide isolated named Parkerin with a unique sequence of
      GWANTLKNVAGGLCKITGAA did not show similarity to any known amphibian AMPs. Multi
      functions of three AMPs were examined (antioxidant, MCD, hemolytic etc). Their
      solution structures determined by CD and antimicrobial mechanisms investigated by
      SEM are very well consistent with their functional characters. Current result
      suggests that these novel multi-functional AMPs could play an important role in
      defending N. parkeri against environmental oxidative stress and pathogenic
      microorganisms, which may partially reveal the ecological adaptation of these
      plateau-living amphibians.

PMID- 20153802
TI  - Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4
      axis: further evidence that innate immunity orchestrates the mobilization of
      hematopoietic stem/progenitor cells.
AB  - OBJECTIVE: Having previously demonstrated that the complement system modulates
      mobilization of hematopoietic stem/progenitor cells (HSPC) in mice, we
      investigated the involvement of C5 cleavage fragments (C5a/(desArg)C5a) in human
      HSPC mobilization. MATERIALS AND METHODS: C5 cleavage fragments in the plasma
      were evaluated by enzyme-linked immunosorbent assay using human anti-(desArg)C5a
      antibody, and expression of the C5a/(desArg)C5a receptor (CD88) in hematopoietic
      cells by flow cytometry. We also examined the chemotactic responses of
      hematopoietic cells to C5 cleavage fragments and expression of stromal cell
      derived factor-1 (SDF-1)-degrading proteases that perturb retention of HSPC in
      bone marrow, namely matrix metalloproteinase (MMP)-9, membrane type (MT) 1-MMP,
      and carboxypeptidase M. RESULTS: We found that plasma levels of (desArg)C5a are
      significantly higher in patients who are good mobilizers and correlate with
      CD34(+) cell and white blood cell counts in mobilized peripheral blood. C5
      cleavage fragments did not chemoattract myeloid progenitors (colony-forming unit
      granulocyte-macrophage), but (desArg)C5a did strongly chemoattract mature
      nucleated cells. Consistently, CD88 was not detected on CD34(+) cells, but
      appeared on more mature myeloid precursors, monocytes, and granulocytes.
      Moreover, granulocyte colony-stimulating factor-mobilized peripheral blood
      mononuclear cells and polymorphonuclear cells had a significantly higher
      percentage of cells expressing CD88 than nonmobilized peripheral blood.
      Furthermore, C5a stimulation of granulocytes and monocytes decreased CXCR4
      expression and chemotaxis toward an SDF-1 gradient and increased secretion of MMP
      9 and expression of MT1-MMP and carboxypeptidase M. CONCLUSION: C5 cleavage
      fragments not only induce a highly proteolytic microenvironment in human bone
      marrow, which perturbs retention through the CXCR4/SDF-1 axis, but also strongly
      chemoattracts granulocytes, promoting their egress into mobilized peripheral
      blood, which is crucial for subsequent mobilization of HSPC.

PMID- 20153803
TI  - The nuclear isoform of the LIM domain protein Trip6 integrates activating and
      repressing signals at the promoter-bound glucocorticoid receptor.
AB  - Trip6 belongs to a family of cytosolic LIM domain proteins involved in cell
      adhesion and migration. Recent findings show that these proteins also regulate
      transcription. We have previously reported that nTrip6, a nuclear isoform of
      Trip6, acts as a co-activator for AP-1 and NF-kappaB transcription factors. Here
      we report that nTrip6 is an essential regulator of glucocorticoid receptor (GR)
      transcriptional activity. nTrip6 is recruited to GR-bound promoters through an
      interaction with GR, and increases GR-mediated transcription. nTrip6 is also
      essential for the transrepression of GR by NF-kappaB and AP-1. The interaction of
      nTrip6 with NF-kappaB and AP-1 at a GR-bound promoter is required for the
      repression. Thus, nTrip6 serves as the molecular mediator of the crosstalk
      between nuclear receptors and other transcription factors in that it assembles
      these factors at promoters. Our results reveal an essential role for LIM domain
      proteins in the integration of positive and negative signals at target promoters.

PMID- 20153804
TI  - Pituitary senescence: the evolving role of Pttg.
AB  - Despite the high prevalence of pituitary adenomas they are invariably benign,
      indicative of unique intrinsic mechanisms controlling pituitary cell
      proliferation. Cellular senescence is characterized by a largely irreversible
      cell cycle arrest and constitutes a strong anti-proliferative response, which can
      be triggered by DNA damage, chromosomal instability and aneuploidy, loss of tumor
      suppressive signaling or oncogene activation. In vivo senescence is an important
      protective mechanism against cancer. Here we discuss prospective mechanisms
      underlying senescence-associated molecular pathways activated in benign pituitary
      adenomas. Both deletion and over-expression of pituitary tumor transforming gene
      (Pttg) promote chromosomal instability and aneuploidy. Pttg deletion abrogates
      tumor development by activating p53/p21-dependent senescence pathways. Abundant
      PTTG in GH-secreting pituitary adenomas also triggers p21-dependent senescence.
      Pituitary p21 may therefore safeguard against further chromosomal instability by
      constraining pituitary tumor growth. These observations point to senescence as a
      target for effective therapy for both tumor silencing and growth restraint
      towards development of pituitary malignancy.

PMID- 20153806
TI  - Genetics and phenomics of hypothyroidism and goiter due to TPO mutations.
AB  - Thyroid peroxidase (TPO) is a heme binding protein localized on the apical
      membrane of the thyrocyte. TPO enzymatic activity is essential for thyroid
      hormonogenesis. Inactivating mutations form the molecular basis for a specific
      subtype of congenital hypothyroidism: thyroid dyshormonogenesis due to an iodide
      organification defect. The most common phenotype of this autosomal recessive
      disease is a total iodide organification defect, with severe and permanent
      hypothyroidism as a consequence. Currently 61 properly annotated mutations in the
      TPO gene have been reported, of which the majority are missense mutations.
      Functional data of most missense mutations is not available, making it necessary
      to revert to in silico methods for functional interpretation of mutations. We
      hypothesize that iodine status is the main phenomic modifier of TPO function.

PMID- 20153805
TI  - Genetics and phenomics of hypothyroidism and goiter due to NIS mutations.
AB  - Molecular cloning of the NIS gene in 1996 allowed examination of the molecular
      basis of congenital hypothyroidism due to iodide transport defect (ITD) many
      years after the first case was described by Federman et al. in 1958. Since 1997,
      when the first NIS mutation causing ITD was identified and characterized, 12
      different NIS molecular defects have been described in 31 ITD patients.
      Interestingly, marked clinical heterogeneity between patients with the same NIS
      mutation and in patients with different mutations in the NIS gene without a clear
      genotype-phenotype correlation has been observed. The study of NIS mutations as
      the molecular basis of ITD has not only yielded extremely valuable
      structure/function information on NIS, but has also provided an important tool
      for preclinical diagnosis and genetic counseling of ITD patients.

PMID- 20153807
TI  - P200 and phonological processing in Chinese word recognition.
AB  - The present study examined the relationship between P200 and phonological
      processing in Chinese word recognition. Participants did a semantic judgment task
      on pairs of words. The critical pairs were all semantically unrelated in one of
      three conditions: homophonic, rhyme, or phonologically unrelated. Noting the
      possibility that P200 may be affected by phonological similarity and orthographic
      similarity and that literature studies may not have assessed such effects
      separately, the present study used visually dissimilar word pairs sharing no
      phonetic radicals. Relative to the control pairs, both the homophonic and rhyme
      pairs elicited a significantly larger P200 with a scalp distribution centering at
      the centro-parietal areas. The results present strong evidence that P200 can be
      modulated by lexical phonology alone, independent of sub-lexical phonology, or
      lexical or sub-lexical orthography. P200 effects were comparable in amplitude and
      topography between the homophonic and the rhyme conditions, suggesting that P200
      is sensitive to phonology at both the syllabic and the sub-syllabic levels.

PMID- 20153808
TI  - Electrophysiological correlates of early processing of visual word recognition:
      N2 as an index of visual category feature processing.
AB  - A fundamental question in second language learning is how the brain separates
      inputs from different languages into distinct representation systems prior to
      semantic activation. The present study investigated this question using a silent
      reading task in which Latin letters and simple Chinese characters (including real
      characters and pseudocharacters) appeared randomly for 100 milliseconds (ms).
      High-density event-related potentials were employed to record the
      electrophysiological correlates of visual word recognition prior to motor
      response. The results showed that real Chinese characters and pseudocharacters
      produced a larger N2 response than letters within 200-300ms time window. However,
      no significant differences between real Chinese characters and pseudocharacters
      were found. The separation of two languages into their own systems might occur in
      the time window when N2 was elicited. The segregation of real Chinese characters
      and pseudocharacters was observed in a later time window (350-450ms). The
      category feature processing of stimuli might be responsible for the N2 response;
      the processing allows stimuli of the same category to be analyzed in their
      specific units and distinguishes different stimuli.

PMID- 20153809
TI  - Amyloid load in nondemented brains correlates with APOE e4.
AB  - 179 Cognitively healthy adults enrolled in the Sun Health Brain Donation program
      between 7/91 and 12/07 were at least 60 years old and nondemented at the time of
      death (21 had developed mild cognitive impairment [MCI]). Amyloid plaque density,
      congophilic amyloid angiopathy (CAA), and neurofibrillary tangle (NFT) density
      scores were based on CERAD criteria and compared in apolipoprotein E (APOE) e4
      carriers (n=42) and noncarriers (NC) (n=137). Mean age (83.4+/-.6), gender (45%
      women), interval between death and brain harvest (3.1+/-2.4h), and brain weight
      (1200+/-119 g) did not differ between e4 carriers (n=42) and NC. Total plaque
      density was higher in e4 carriers than NC (6.8+/-4.9 vs. 4.3+/-4.4, p=.002), and
      this was true in each of 5 subregions examined. Total CAA (p=.002) and all
      subregion CAA burden was also higher in e4 carriers. Total neuritic plaque
      density (1.2+/-1.0 vs. 1.0+/-1.0, p=.18) and total NFT density (3.9+/-2.4 vs.
      3.6+/-2.3, p=.50) did not differ between e4 carriers and NC, nor in any
      subregion. Eliminating the 21 with MCI did not alter these results. Nondemented
      APOE e4 carriers over age 60 have a higher burden of total parenchymal and
      vascular amyloid neuropathology than NC, but no difference in neuritic plaque and
      NFT pathology.

PMID- 20153810
TI  - Neuronal activities of forebrain structures with respect to bladder contraction
      in cats.
AB  - The forebrain is one of the important suprapontine micturition centres. Previous
      studies have shown that electrical stimulation of the frontal lobe and the
      anterior cingulate gyrus elicited either inhibition or facilitation of bladder
      contraction. Patients with frontal lobe tumours and aneurysms showed micturition
      disorders. Functional brain imaging studies showed that several parts of the
      forebrain are activated during bladder filling. We aimed to examine neuronal
      activities of forebrain structures with respect to bladder contraction in cats.
      In 14 adult male cats under ketamine anaesthesia in which a spontaneous
      isovolumetric bladder-contraction/relaxation cycle had been generated, we carried
      out extracellular single-unit recording in forebrain with respect to the
      contraction/relaxation cycles in the bladder. We recorded 112 neurons that were
      related to the bladder-contraction/relaxation cycles. Ninety-four neurons were
      found to be tonically activated during the bladder-relaxation phase, whereas the
      remaining 18 neurons were tonically activated during the bladder-contraction
      phase. Both types of neuron were widely distributed around the cruciate sulcus.
      Most were located medially (medial and superior frontal gyrus) and the rest were
      located laterally (middle and inferior frontal gyrus). Neurons recorded in
      forebrain structures were activated with respect to the contraction/relaxation
      cycles in the bladder. Forebrain structures may have a significant role in
      regulating bladder contraction in cats.

PMID- 20153811
TI  - Cytokines and chemokines in viral encephalitis: a clinicoradiological
      correlation.
AB  - Japanese encephalitis (JE) is the commonest encephalitis in South East Asia
      associated with high morbidity and mortality. Neuronal injury is attributed to a
      number of proinflammatory cytokines. This study evaluates cerebrospinal fluid
      (CSF) cytokines and chemokines in encephalitis and correlates these with clinical
      and magnetic resonance imaging (MRI) findings. We examined 14 patients with
      encephalitis (8 JE, 1 dengue, 5 nonspecific encephalitis) and 10 healthy
      controls. CSF cytokines (IL-1beta, IL-6, IL-10, IL-12p70, TNF-alpha, IL-8) and
      chemokines (IP-10, MCP-1, MIG, IL-8 and RANTES) were estimated using Cytometric
      Bead Array, compared with controls and were correlated with severity of
      encephalitis, radiological findings and presence of movement disorders. Median
      age of the patients was 25.5 (range 6-55 years); 6 had seizures, 10 movement
      disorders and 6 out of 11 had MRI abnormalities. The MRI abnormalities included
      thalamic involvement in 5, basal ganglia and mid brain in 3 each and cortical
      involvement in 2 patients. Both the patients with cortical involvement had
      seizures and 5 of the 10 patients with movement disorders had thalamic, basal
      ganglia and/or mid brain involvement. There was significant increase in IL-6
      (p=0.01), RANTES (p=0.02) and IL-8 (p=0.02) in encephalitis compared to controls
      but there was no difference in IL12p70, TNF-alpha, IL-10, IL-1beta and MCP-1.
      Cytokines and chemokines did not correlate with severity of encephalitis,
      radiological changes and presence of movement disorders. CSF IL-6, IL-8 and
      RANTES were significantly higher in encephalitis patients compared to controls.

PMID- 20153812
TI  - Muscle transfection and permeabilization induced by electrotransfer or pluronic
      L64: Paired study by optical imaging and MRI.
AB  - BACKGROUND: Muscle transfection by electrotranfer is an efficient currently used
      procedure. Recently, the block copolymer pluronic L64 has been reported to
      improve muscle transfection. Both procedures are known to permeabilize muscle
      fibres. Relation between muscle transfection and permeabilization by
      electrotransfer and L64 was investigated herein. METHODS: Muscle transfection was
      evaluated by optical detection of the luciferase reporter gene activity. Muscle
      permeabilization was evaluated by the uptake of the T1 contrast agent gadolinium
      Dotarem (Gd-DOTA) using Magnetic resonance imaging (MRI). Histological
      examination of muscle sections was also performed. RESULTS: Electrotransfer and
      L64 (at a 0.25% concentration) similarly improved muscle transfection, although
      the interindividual variability was higher for pluronic. On the same animals, the
      permeabilized volume to the Gd-DOTA was significantly increased after
      electrotransfer, and L64 from 0.1% to 1%. The concentration of the Gd-DOTA in the
      permeabilized volume was significantly increased after electrotransfer and L64 at
      0.5% and 1%. By histological observation, the inflammation was maximum at day 3
      after electrotransfer or L64 injection, and mostly reversed after 7 days. The
      permeabilized volume and the transfection level correlated for the set of all the
      conditions tested. However, no significant correlation was observed between Gd
      DOTA concentration and transfection. GENERAL SIGNIFICANCE: It is possible to use
      successively on the same animals MRI and optical imaging for paired studies of
      muscle transfection and permeabilization. Permeabilization is possibly not
      related to gene transfer but it indicates membrane modification related to
      transfection by the electrotransfer or co-injection of DNA with the L64.

PMID- 20153813
TI  - Spatio-temporal dynamics of olfactory processing in the human brain: an event
      related source imaging study.
AB  - Although brain structures involved in central nervous olfactory processing in
      humans have been well identified with functional neuroimaging, little is known
      about the temporal sequence of their activation. We recorded olfactory event
      related potentials (ERP) to H(2)S stimuli presented to the left and right nostril
      in 12 healthy subjects. Topographic and source analysis identified four distinct
      processing steps between 200 and 1000 ms. Activation started ipsilateral to the
      stimulated nostril in the mesial and lateral temporal cortex (amygdala,
      parahippocampal gyrus, superior temporal gyrus, insula). Subsequently, the
      corresponding structures on the contralateral side became involved, followed by
      frontal structures at the end of the activation period. Thus, based on EEG
      related data, current results suggest that olfactory information in humans is
      processed first ipsilaterally to the stimulated nostril and then activates the
      major relays in olfactory information processing in both hemispheres. Most
      importantly, the currently described techniques allow the investigation of the
      spatial processing of olfactory information at a high temporal resolution.

PMID- 20153815
TI  - Telithromycin blocks neuromuscular transmission and inhibits nAChR currents in
      vitro.
AB  - Telithromycin, a ketolide antibiotic, is reported to exacerbate myasthenia
      gravis, potentially leading to respiratory failure and death. However,
      telithromycin is not associated with neuromuscular effects in animal toxicity
      studies. The objective of this study was to examine the effect of telithromycin
      on the neuromuscular junction in the isolated rat phrenic nerve-diaphragm
      preparation and to investigate its postsynaptic effects on the muscle-like
      nicotinic acetylcholine (ACh) receptors expressed on human TE671 cells.
      Telithromycin decreased the twitch contraction force of the rat diaphragm muscle
      in response to phrenic nerve stimulation in a concentration-dependent manner with
      an IC(50) of 22.3 microM and a maximal inhibition of approximately 70%. The trans
      membrane current from the ACh receptors expressed in the TE671
      neuromedulloblastoma cells was recorded in the whole-cell patch-clamp
      configuration. When applied to the TE671 cells, telithromycin caused a dose
      dependent inhibition of the nicotinic ACh current with an IC(50) of 3.5 microM
      and maximal inhibition of nearly 100%. These results indicate that telithromycin
      inhibits postsynaptic nicotinic ACh receptors in vitro and partially blocks
      neuromuscular transmission in the isolated rat phrenic nerve-diaphragm
      preparation. Based on these findings, we propose that exacerbation of myasthenia
      gravis reported in some patients taking telithromycin results in part from
      postsynaptic neuromuscular transmission block.

PMID- 20153814
TI  - Sensory afferent and hypoxia-mediated activation of nucleus tractus solitarius
      neurons that project to the rostral ventrolateral medulla.
AB  - The nucleus tractus solitarius (nTS) of the brainstem receives sensory afferent
      inputs, processes that information, and sends projections to a variety of brain
      regions responsible for influencing autonomic and respiratory output. The nTS
      sends direct projections to the rostral ventrolateral medulla (RVLM), an area
      important for cardiorespiratory reflexes and homeostasis. Since the net reflex
      effect of nTS processing ultimately depends on the properties of output neurons,
      we determined the characteristics of these RVLM-projecting nTS neurons using
      electrophysiological and immunohistochemical techniques. RVLM-projecting nTS
      neurons were identified by retrograde tracers. Patch clamp analysis in the
      horizontal brainstem nTS slice demonstrated that RVLM-projecting nTS cells
      exhibit constant latency solitary tract evoked excitatory postsynaptic currents
      (EPSCs), suggesting they receive strong monosynaptic contacts from visceral
      afferents. Three distinct patterns of action potential firing, associated with
      different underlying potassium currents, were observed in RVLM-projecting cells.
      Following activation of the chemoreflex in conscious animals by 3 h of acute
      hypoxia, 11.2+/-1.9% of the RVLM-projecting nTS neurons were activated, as
      indicated by positive Fos-immunoreactivity. Very few RVLM-projecting nTS cells
      were catecholaminergic. Taken together, these data suggest that RVLM projecting
      nTS neurons receive strong monosynaptic inputs from sensory afferents and a
      subpopulation participates in the chemoreflex pathway.

PMID- 20153816
TI  - Pharmaceutical nanoparticles--from their innovative origin to their future.

PMID- 20153817
TI  - Justice, insurance, and biomarkers of aging.
AB  - Insurers will want to use biomarkers of aging to decide whom to insure and how
      much to charge. If insurers are allowed to use biomarker information, then people
      whose biomarkers indicate shorter or more afflicted lives will find insurance
      harder to get and more expensive, while the longer-lived and less afflicted will
      find it cheaper and easier to get. If insurers are forbidden to use such
      information, then these two groups will be in a more equal position with regards
      to insurance-as they are now, in the absence of such information. Does society
      have a moral responsibility to address such natural inequalities? If so, then
      insurers should be forbidden to use such information. I will discuss arguments on
      both sides of this issue, and argue that justice requires preventing insurers
      from obtaining and using biomarker information.

PMID- 20153818
TI  - Perspectives on the mitochondrial etiology of replicative aging in yeast.
AB  - In a now classical paper, Denham Harman suggested that free radicals produced
      during mitochondrial respiration cause cumulative oxidative damage, resulting in
      aging and age-related disorders and pathologies. Proponents of this hypothesis
      have focused their attention, not surprisingly, on mitochondria arguing that
      these organelles may serve as the biological clock for aging. Indeed, work on
      many models, including filamentous fungi, nematodes, and mammals have revealed
      that age-dependent reorganizations of the mitochondrial DNA (mtDNA) may play a
      central role in the aging of these organisms. Furthermore, genetic alterations of
      mitochondrial function may either shorten or extend life span. In this paper, we
      focus on the role of mitochondria in the replicative aging of yeast mother cells,
      whether this role of mitochondria is really a linked to altered ROS production
      and/or respiration, and highlight some important questions that remain to be
      answered.

PMID- 20153819
TI  - Intracerebroventricular ouabain administration induces oxidative stress in the
      rat brain.
AB  - Intracerebroventricular (ICV) injection of ouabain (a potent Na(+)/K(+)-ATPase
      inhibitor) in rats resulted in manic-like effects. There is an emerging body of
      data indicating that major neuropsychiatric disorders, such as bipolar disorder
      and schizophrenia, are associated with increased oxidative stress. In this study,
      we investigated the effects of ICV ouabain injection on oxidative stress
      parameters in total tissue of rat brain. Our findings demonstrated that ICV
      injection increased thiobarbituric acid reactive species levels and protein
      carbonyl generation in the prefrontal cortex and hippocampus of rats. Moreover,
      the activity of the antioxidants enzymes catalase and superoxide dismutase was
      altered in several areas of the rat brain and cerebrospinal fluid of ICV ouabain
      subjected rats. These results showed that Na(+)/K(+)-ATPase inhibition can lead
      to oxidative stress in the brain of rats.

PMID- 20153820
TI  - Characterization of a Caenorhabditis elegans glc seven-like phosphatase (gsp)
      orthologue from Haemonchus contortus (Nematoda).
AB  - A full-length complementary DNA (cDNA; designated Hc-stp-1) encoding a
      serine/threonine phosphatase (Hc-STP-1) was isolated from Haemonchus contortus, a
      strongylid nematode parasite of small ruminants. Hc-stp-1 was shown to be
      transcribed in males of both adults and fourth-stage larvae, but not in females,
      early larval stages or eggs. The full-length gene (2854 bp) contained ten exons
      and nine introns, and encoded a cDNA of 951 bp. Comparisons of the conceptually
      translated protein (316 amino acids, estimated at approximately 35 kDa) with
      serine/threonine phosphatases (STPs) from other organisms revealed the presence
      of the conserved motif LRGNHE. Structural analysis, by comparative modelling,
      confirmed strict conservation of residues and features involved in catalytic
      activity, and variation in the ligand-binding interface. Phylogenetic analysis of
      amino acid sequence data revealed that Hc-STP-1 clustered with STPs from other
      nematodes (including Caenorhabditis elegans, Trichostrongylus vitrinus,
      Oesophagostomum dentatum, Ascaris suum and Brugia malayi) to the exclusion of
      STPs from other organisms. The protein was inferred to be most closely related to
      the PP1 class of STPs of C. elegans, within a group containing STPs encoded,
      amongst others, by the genes gsp-3 and gsp-4 in this free-living nematode. The
      functions of proteins GSP-3 and GSP-4 are known to be central to spermatogenesis
      and other male-specific processes in C. elegans. The findings from the present
      and previous studies support the proposal that Hc-stp-1 and its product play a
      significant role in reproductive and/or developmental processes in maturing or
      adult male H. contortus.

PMID- 20153823
TI  - ISG15 and immune diseases.
AB  - ISG15, the product of interferon (IFN)-stimulated gene 15, is the first
      identified ubiquitin-like protein, consisting of two ubiquitin-like domains.
      ISG15 is synthesized as a precursor in certain mammals and, therefore, needs to
      be processed to expose the C-terminal glycine residue before conjugation to
      target proteins. A set of three-step cascade enzymes, an E1 enzyme (UBE1L), an E2
      enzyme (UbcH8), and one of several E3 ligases (e.g., EFP and HERC5), catalyzes
      ISG15 conjugation (ISGylation) of a specific protein. These enzymes are unique
      among the cascade enzymes for ubiquitin and other ubiquitin-like proteins in that
      all of them are induced by type I IFNs or other stimuli, such as exposure to
      viruses and lipopolysaccharide. Mass spectrometric analysis has led to the
      identification of several hundreds of candidate proteins that can be conjugated
      by ISG15. Some of them are type I IFN-induced proteins, such as PKR and RIG-I,
      and some are the key regulators that are involved in IFN signaling, such as JAK1
      and STAT1, implicating the role of ISG15 and its conjugates in type I IFN
      mediated innate immune responses. However, relatively little is known about the
      functional significance of ISG15 induction due to the lack of information on the
      consequences of its conjugation to target proteins. Here, we describe the recent
      progress made in exploring the biological function of ISG15 and its reversible
      modification of target proteins and thus in their implication in immune diseases.

PMID- 20153822
TI  - Functional analysis of H. sapiens DNA polymerase gamma spacer mutation W748S with
      and without common variant E1143G.
AB  - Mitochondrial DNA polymerase, POLG, is the sole DNA polymerase found in animal
      mitochondria. In humans, POLGalpha W748S in cis with an E1143G mutation has been
      linked to a new type of recessive ataxia, MIRAS, which is the most common
      inherited ataxia in Finland. We investigated the biochemical phenotypes of the
      W748S amino acid change, using recombinant human POLG. We measured processive and
      non-processive DNA polymerase activity, DNA binding affinity, enzyme
      processivity, and subunit interaction with recombinant POLGbeta. In addition, we
      studied the effects of the W748S and E1143G mutations in primary human cell
      cultures using retroviral transduction. Here, we examined cell viability,
      mitochondrial DNA copy number, and products of mitochondrial translation. Our
      results indicate that the W748S mutant POLGalpha does not exhibit a clear
      biochemical phenotype, making it indistinguishable from wild type POLGalpha and
      as such, fail to replicate previously published results. Furthermore, results
      from the cell models were concurrent with the findings from patients, and support
      our biochemical findings.

PMID- 20153821
TI  - Roles for the type III TGF-beta receptor in human cancer.
AB  - Transforming growth factor beta (TGF-beta) superfamily ligands have important
      roles in regulating cellular homeostasis, embryonic development, differentiation,
      proliferation, immune surveillance, angiogenesis, motility, and apoptosis in a
      cell type and context specific manner. TGF-beta superfamily signaling pathways
      also have diverse roles in human cancer, functioning to either suppress or
      promote cancer progression. The TGF-beta superfamily co-receptor, the type III
      TGF-beta receptor (TbetaRIII, also known as betaglycan) mediates TGF-beta
      superfamily ligand dependent as well as ligand independent signaling to both Smad
      and non-Smad signaling pathways. Loss of TbetaRIII expression during cancer
      progression and direct effects of TbetaRIII on regulating cell migration,
      invasion, proliferation, and angiogenesis support a role for TbetaRIII as a
      suppressor of cancer progression and/or as a metastasis suppressor. Defining the
      physiological function and mechanism of TbetaRIII action and alterations in
      TbetaRIII function during cancer progression should enable more effective
      targeting of TbetaRIII and TbetaRIII mediated functions for the diagnosis and
      treatment of human cancer.

PMID- 20153825
TI  - Mitochondrial bioenergetics and dynamics interplay in complex I-deficient
      fibroblasts.
AB  - BACKGROUND: Complex I (CI) deficiency is the most frequent cause of OXPHOS
      disorders. Recent studies have shown increases in reactive oxygen species (ROS)
      production and mitochondrial network disturbances in patients' fibroblasts
      harbouring mutations in CI subunits. OBJECTIVES: The present work evaluates the
      impact of mutations in the NDUFA1 and NDUFV1 genes of CI on mitochondrial
      bioenergetics and dynamics, in fibroblasts from patients suffering isolated CI
      deficiency. RESULTS: Decreased oxygen consumption rate and slow growth rate were
      found in patients with severe CI deficiency. Mitochondrial diameter was slightly
      increased in patients' cells cultured in galactose or treated with 2'
      deoxyglucose without evidence of mitochondrial fragmentation. Expression levels
      of the main proteins involved in mitochondrial dynamics, OPA1, MFN2, and DRP1,
      were slightly augmented in all patients' cells lines. The study of mitochondrial
      dynamics showed delayed recovery of the mitochondrial network after treatment
      with the uncoupler carbonyl cyanide m-chlorophenyl hydrazone (cccp) in patients
      with severe CI deficiency. Intracellular ROS levels were not increased neither in
      glucose nor galactose medium in patients' fibroblasts. CONCLUSION: Our main
      finding was that severe CI deficiency in patients harbouring mutations in the
      NDUFA1 and NDUFV1 genes is linked to a delayed mitochondrial network recovery
      after cccp treatment. However, the CI deficiency is neither associated with
      massive mitochondrial fragmentation nor with increased ROS levels. The different
      genetic backgrounds of patients with OXPHOS disorders would explain, at least
      partially, differences in the pathophysiological manifestations of CI deficiency.

PMID- 20153824
TI  - Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood
      pressure regulation.
AB  - Complex interactions between genes and environment result in a sodium-induced
      elevation in blood pressure (salt sensitivity) and/or hypertension that lead to
      significant morbidity and mortality affecting up to 25% of the middle-aged adult
      population worldwide. Determining the etiology of genetic and/or environmentally
      induced high blood pressure has been difficult because of the many interacting
      systems involved. Two main pathways have been implicated as principal
      determinants of blood pressure since they are located in the kidney (the key
      organ responsible for blood pressure regulation), and have profound effects on
      sodium balance: the dopaminergic and renin-angiotensin systems. These systems
      counteract or modulate each other, in concert with a host of intracellular second
      messenger pathways to regulate sodium and water balance. In particular, the G
      protein-coupled receptor kinase type 4 (GRK4) appears to play a key role in
      regulating dopaminergic-mediated natriuresis. Constitutively activated GRK4 gene
      variants (R65L, A142V, and A486V), by themselves or by their interaction with
      other genes involved in blood pressure regulation, are associated with essential
      hypertension and/or salt-sensitive hypertension in several ethnic groups.
      GRK4gamma ?142V?transgenic mice are hypertensive on normal salt intake while
      GRK4gamma? 486V? transgenic mice develop hypertension only with an increase in
      salt intake. GRK4 gene variants have been shown to hyperphosphorylate,
      desensitize, and internalize two members of the dopamine receptor family, the
      D(1) (D(1)R) and D(3) (D(3)R) dopamine receptors, but also increase the
      expression of a key receptor of the renin-angiotensin system, the angiotensin
      type 1 receptor (AT(1)R). Knowledge of the numerous blood pressure regulatory
      pathways involving angiotensin and dopamine may provide new therapeutic
      approaches to the pharmacological regulation of sodium excretion and ultimately
      blood pressure control.

PMID- 20153826
TI  - Matrix metalloproteinase-3 in articular cartilage is upregulated by joint
      immobilization and suppressed by passive joint motion.
AB  - Both underloading and overloading of joints can lead to articular cartilage
      degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here
      we examine the effects of reduced loading of rat hindlimbs on articular cartilage
      expression of MMP-3, which not only digests matrix components but also activates
      other proteolytic enzymes. We show that hindlimb immobilization resulted in
      elevated MMP-3 mRNA expression at 6h that was sustained throughout the 21day
      immobilization period. MMP-3 upregulation was higher in the medial condyle than
      the lateral, and was greatest in the superficial cartilage zone, followed by
      middle and deep zones. These areas also showed decreases in safranin O staining,
      consistent with reduced cartilage proteoglycan content, as early as 7days after
      immobilization. One hour of daily moderate mechanical loading, applied as passive
      joint motion, reduced the MMP-3 and ADAMTS-5 increases that resulted from
      immobilization, and also prevented changes in safranin O staining. Intra
      articular injections of an MMP-3 inhibitor, N-isobutyl-N-(4
      methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), dampened the catabolic
      effects of a 7day immobilization period, indicating a likely requirement for MMP
      3 in the regulation of proteoglycan levels through ADAMTS-5. These results
      suggest that biomechanical forces have the potential to combat cartilage
      destruction and can be critical in developing effective therapeutic strategies.

PMID- 20153827
TI  - Adult equine bone marrow stromal cells produce a cartilage-like ECM mechanically
      superior to animal-matched adult chondrocytes.
AB  - Our objective was to evaluate the age-dependent mechanical phenotype of bone
      marrow stromal cell- (BMSC-) and chondrocyte-produced cartilage-like neo-tissue
      and to elucidate the matrix-associated mechanisms which generate this phenotype.
      Cells from both immature (2-4 month-old foals) and skeletally-mature (2-5 year
      old adults) mixed-breed horses were isolated from animal-matched bone marrow and
      cartilage tissue, encapsulated in self-assembling-peptide hydrogels, and cultured
      with and without TGF-beta1 supplementation. BMSCs and chondrocytes from both
      donor ages were encapsulated with high viability. BMSCs from both ages produced
      neo-tissue with higher mechanical stiffness than that produced by either young or
      adult chondrocytes. Young, but not adult, chondrocytes proliferated in response
      to TGF-beta1 while BMSCs from both age groups proliferated with TGF-beta1. Young
      chondrocytes stimulated by TGF-beta1 accumulated ECM with 10-fold higher sulfated
      glycosaminoglycan content than adult chondrocytes and 2-3-fold higher than BMSCs
      of either age. The opposite trend was observed for hydroxyproline content, with
      BMSCs accumulating 2-3-fold more than chondrocytes, independent of age. Size
      exclusion chromatography of extracted proteoglycans showed that an aggrecan-like
      peak was the predominant sulfated proteoglycan for all cell types. Direct
      measurement of aggrecan core protein length and chondroitin sulfate chain length
      by single molecule atomic force microscopy imaging revealed that, independent of
      age, BMSCs produced longer core protein and longer chondroitin sulfate chains,
      and fewer short core protein molecules than chondrocytes, suggesting that the
      BMSC-produced aggrecan has a phenotype more characteristic of young tissue than
      chondrocyte-produced aggrecan. Aggrecan ultrastructure, ECM composition, and
      cellular proliferation combine to suggest a mechanism by which BMSCs produce a
      superior cartilage-like neo-tissue than either young or adult chondrocytes.

PMID- 20153828
TI  - Identification and characterization of an androgen-responsive Kap promoter
      enhancer located in the intron II region of human angiotensinogen gene.
AB  - Transgenic expression of the human angiotensinogen (HAGT) gene directed by the
      mouse kidney androgen-regulated protein (Kap) gene promoter is proximal tubule
      cell-specific and androgen-regulated in vivo. The same Kap promoter fragment did
      not support similar regulation of other genes, but a transgene based on the
      original chimeric KAP-hAGT construct successfully directed NHE3 to kidney,
      suggesting that sequences within the HAGT gene fragment of the construct
      contributed to the regulation of its expression in vivo. In the present study,
      androgen-responsive regulatory sequences in the HAGT gene portions of the
      transgene were examined in transfected renal cells. A 1.4-kb enhancer between
      exons 2 and 3 was identified that increased the basal expression of Kap promoter
      1.5- to 2-fold, its induction by dihydrotestosterone (DHT) 2- to 3-fold and its
      induction by dexamethasone (Dex) 4- to 5-fold. Sequence analysis revealed two
      potential hormone-responsive elements. Mutational assays and electrophoretic
      mobility shift assay showed one of these elements was androgen-specific. These
      findings may influence future strategies for the design of inducible, cell
      specific transgenes.

PMID- 20153829
TI  - Synthesis and biological evaluation of 6-methyl analog of 1alpha,25
      dihydroxyvitamin D3.
AB  - Among more than 3000 analogs of 1alpha,25-dihydroxyvitamin D3 synthesized to
      date, only a few were characterized by structural modifications in the seco-B
      ring. The compounds alkylated at C-6 seemed to be interesting targets for
      synthetic efforts. Such vitamin D analogs easily undergo thermal conversion to
      their previtamin forms. The results of molecular modeling indicate that
      significant deviation from planarity must be present in their molecules
      associated with the interaction of the 6-alkyl substituent and hydrogens from the
      C-ring. The synthesis of the analog of 1alpha,25-(OH)2D3, being characterized by
      the presence of the 6-methyl group, is reported here, together with the results
      of preliminary testing of its biological potency. This 6-alkylated compound was
      efficiently prepared using a novel stereoconvergent strategy in which the ring A
      and the triene unit of the vitamin D skeleton are constructed by a one-pot Pd
      catalyzed tandem cyclization-Negishi coupling process.

PMID- 20153830
TI  - Impaired cerebellar development and deficits in motor coordination in mice
      lacking the neuronal protein BM88/Cend1.
AB  - During nervous system development, neural progenitors arise in proliferative
      zones, then exit the cell cycle and differentiate as they migrate away from these
      zones. The neuronal protein BM88/Cend1 has been implicated in coordination of
      cell cycle exit and differentiation of neuronal precursors. To further elucidate
      its function we generated Cend1 knock-out mice and analyzed their phenotype
      during postnatal cerebellar development. Cend1(-/-) mice showed no overt
      abnormalities in the gross anatomy of the cerebellum or other brain regions.
      However, detailed analysis revealed alterations in cerebellar layering arising
      from increased proliferation of granule cell precursors, delayed radial granule
      cell migration and impaired Purkinje cell differentiation. Accordingly,
      expression of Patched1, cyclin D1, reelin and brain-derived neurotrophic factor,
      which correlate with morphological development of the cerebellum, was altered in
      Cend1(-/-) mice. The observed anatomical and molecular alterations were
      accompanied by deficits in motor behaviour. Our results suggest that Cend1 is
      required for normal cerebellar development.

PMID- 20153832
TI  - Molecular evidence for the existence of lipopolysaccharide-induced TNF-alpha
      factor (LITAF) and Rel/NF-kB pathways in disk abalone (Haliotis discus discus).
AB  - The lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel family nuclear
      factor kappaB (Rel/NF-kB) are two important transcription factors which play
      major roles in the regulating inflammatory cytokine, apoptosis and immune related
      genes. Here, we report the discovery of disk abalone LITAF (AbLITAF) and Rel/NF
      kB (AbRel/NF-kB) homologues and their immune responses. Full-length cDNA of
      AbLITAF consists of 441 bp open reading frame (ORF) that translates into putative
      peptide of 147 aa. Analysis of AbLITAF sequence showed it has characteristic
      LITAF (Zn(+2)) binding domain with two CXXC motifs. Phylogenetic analysis results
      further revealed that AbLITAF is a member of LITAF family. AbRel/NF-kB is 584 aa
      protein that contains several characteristic motifs including Rel homology domain
      (RHD), Rel protein signature, DNA binding motif, nuclear localization signal
      (NLS) and transcription factor immunoglobulin - like fold (TIG) similar to their
      invertebrate and vertebrate counterparts. Tissue specific analysis results showed
      that both AbLITAF and AbRel/NF-kB mRNA was expressed ubiquitously in all selected
      tissues in constitutive manner. However, constitutive expression of AbLITAF was
      higher than AbRel/NF-kB in all tissues except mantle. Upon immune challenge by
      bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Lysteria
      monocytogenes) and viral hemoragic septicemia virus (VHSV), AbLITAF showed the
      significant up-regulation in gills while AbRel/NF-kB transcription was not change
      significantly. Based on transcriptional response against immune challenge, we
      could suggest that regulation of TNF-alpha expression may have occurred mainly by
      LITAF activation rather than NF-kB in disk abalone. The cumulative data from
      other molluscs and our data with reference to TNF-alpha, LITAF and Rel/NF-kB from
      disk abalone provide strong evidence that LITAF and NF-kB are independent
      pathways likely to occur throughout the Phylum mollusca.

PMID- 20153831
TI  - Rapid purification of helicase proteins and in vitro analysis of helicase
      activity.
AB  - Most processes involving an organism's genetic material, including replication,
      repair and recombination, require access to single-stranded DNA as a template or
      reaction intermediate. To disrupt the hydrogen bonds between the two strands in
      double-stranded DNA, organisms utilize proteins called DNA helicases. DNA
      helicases use duplex DNA as a substrate to create single-stranded DNA in a
      reaction that requires ATP hydrolysis. Due to their critical role in cellular
      function, understanding the reaction catalyzed by helicases is essential to
      understanding DNA metabolism. Helicases are also important in many disease
      processes due to their role in DNA maintenance and replication. Here we discuss
      ways to rapidly purify helicases in sufficient quantity for biochemical analysis.
      We also briefly discuss potential substrates to use with helicases to establish
      some of their critical biochemical parameters. Through the use of methods that
      simplify the study of helicases, our understanding of these essential proteins
      can be accelerated.

PMID- 20153833
TI  - Improved tractography alignment using combined volumetric and surface
      registration.
AB  - Previously we introduced an automated high-dimensional non-linear registration
      framework, CVS, that combines volumetric and surface-based alignment to achieve
      robust and accurate correspondence in both cortical and sub-cortical regions
      (Postelnicu et al., 2009). In this paper we show that using CVS to compute cross
      subject alignment from anatomical images, then applying the previously computed
      alignment to diffusion weighted MRI images, outperforms state-of-the-art
      techniques for computing cross-subject alignment directly from the DWI data
      itself. Specifically, we show that CVS outperforms the alignment component of
      TBSS in terms of degree-of-alignment of manually labeled tract models for the
      uncinate fasciculus, the inferior longitudinal fasciculus and the corticospinal
      tract. In addition, we compare linear alignment using FLIRT based on either
      fractional anisotropy or anatomical volumes across-subjects, and find a
      comparable effect. Together these results imply a clear advantage to aligning
      anatomy as opposed to lower resolution DWI data even when the final goal is
      diffusion analysis.

PMID- 20153834
TI  - A group model for stable multi-subject ICA on fMRI datasets.
AB  - Spatial Independent Component Analysis (ICA) is an increasingly used data-driven
      method to analyze functional Magnetic Resonance Imaging (fMRI) data. To date, it
      has been used to extract sets of mutually correlated brain regions without prior
      information on the time course of these regions. Some of these sets of regions,
      interpreted as functional networks, have recently been used to provide markers of
      brain diseases and open the road to paradigm-free population comparisons. Such
      group studies raise the question of modeling subject variability within ICA: how
      can the patterns representative of a group be modeled and estimated via ICA for
      reliable inter-group comparisons? In this paper, we propose a hierarchical model
      for patterns in multi-subject fMRI datasets, akin to mixed-effect group models
      used in linear-model-based analysis. We introduce an estimation procedure, CanICA
      (Canonical ICA), based on i) probabilistic dimension reduction of the individual
      data, ii) canonical correlation analysis to identify a data subspace common to
      the group iii) ICA-based pattern extraction. In addition, we introduce a
      procedure based on cross-validation to quantify the stability of ICA patterns at
      the level of the group. We compare our method with state-of-the-art multi-subject
      fMRI ICA methods and show that the features extracted using our procedure are
      more reproducible at the group level on two datasets of 12 healthy controls: a
      resting-state and a functional localizer study.

PMID- 20153835
TI  - Troubleshooting methods for APP processing in vitro.
AB  - INTRODUCTION: The amyloid hypothesis states that Abeta is the main trigger for
      Alzheimer's disease. This report is focused in the study of the processing of the
      Amyloid Precursor Protein (APP) as a procedure to investigate the molecular
      mechanisms that may result in changes in the levels of Abeta. METHODS: Here we
      analyse different methodologies for Abeta determination, soluble APP, APP-Carboxy
      terminus fragments (CTFs) and enzymes for synthesis (secretases) and degradation
      of Abeta. In addition the advantages and disadvantages of different methodologies
      are discussed. DISCUSSION: The potential value of these procedures is described
      in the context of the function of APP and the different fragments derived from
      its cleavage.

PMID- 20153836
TI  - Chronic kidney disease, thrombotic microangiopathy, and hypertension following T
      cell-depleted hematopoietic stem cell transplantation.
AB  - Chronic kidney disease (CKD) is now an accepted long-term complication of
      allogeneic hematopoietic stem cell transplantation. Calcineurin inhibitors (CNI),
      which are used for prophylaxis and treatment of graft-versus-host disease (GVHD),
      have been associated with the development of nephrotoxicity. Hypertension (HTN)
      and thrombotic microangiopathy (TMA) are 2 comorbidities linked to CKD. T cell
      depletion (TCD) of stem cell grafts can obviate the need for the use of CNI. We
      conducted a retrospective analysis of 100 patients who underwent TCD
      transplantation: 30 in group A were conditioned without total-body radiation
      (TBI) and 70 in group B received a TBI containing regimen. None of the patients
      received CNI. The median age was 55.5 and 45 years for groups A and B,
      respectively. Eleven patients developed TMA, all in group B. The 2-year
      cumulative incidence of sustained CKD was 29.2% and 48.8% in group A and group B,
      respectively, with a mean follow-up of at least 21 months. CKD free survival was
      better in the non-TBI group (P = .046). Multivariable survival analysis revealed
      that exposure to TBI, older age, and TMA were risk factors for CKD. The incidence
      of new onset or worsening HTN was 6.7% and 25.7% (P = .03) in group A and B,
      respectively. The use of TBI (P = .0182) and diagnosis of TMA (P = .0006)
      predisposed patients to the development of HTN using univariable logistic
      regression models. Thus, despite the absence of CNI, a proportion of these older
      patients in both groups developed CKD and HTN.

PMID- 20153837
TI  - Functional analysis of the pH responsive pathway Pal/Rim in the phytopathogenic
      basidiomycete Ustilago maydis.
AB  - The most important mechanism for fungal response to the environmental pH is the
      Rim or Pal pathway. Details on its operation are known through the analysis of
      ascomycete fungi. In this study we analyzed whether this pathway is conserved in
      a basidiomycete, Ustilago maydis. We could identify only five homologues of the
      seven known components of the pathway in the U. maydis as well as in other
      basidiomycete genomes. We determined that only genes encoding Rim20/PalA,
      Rim13/PalB and Rim23/PalC, that constitute the endosomal membrane complex, and
      Rim9/PalI of the complex located at the plasma membrane are conserved, but this
      latter lacked a detectable role in signal transduction. Mutants in this pathway
      showed a pleiotropic phenotype, but dimorphism and virulence were not affected.
      Our data reveal that the Rim/Pal pathway is conserved in basidiomycetes, but with
      notable differences to the ascomycete systems.

PMID- 20153838
TI  - Characterization of alpha-phosphoglucomutase isozymes from Toxoplasma gondii.
AB  - The Toxoplasma gondii genome project has revealed two putative isoforms (TgPGM-I
      and TgPGM-II) of alpha-phosphoglucomutase (EC 5.4.2.2). We obtained recombinant
      proteins of these isoforms from the Beverley strain of T. gondii and
      characterized their properties, particularly the kinetic properties of these
      isoforms. The specific activities of TgPGM-I and TgPGM-II for alpha-D-glucose 1
      phosphate were 338+/-9 and 84+/-6micromol/min/mg protein, respectively, at 37
      degrees C under optimal conditions. The Kcat and Km values of TgPGM-I were 398+/
      11/s and 0.19+/-0.03mM and those for TgPGM-II were 93+/-7/s and 3.53+/-0.91mM,
      respectively, for alpha-d-glucose 1-phosphate. Magnesium ions were the most
      effective divalent cations for both the enzyme activities. The maximum activities
      of both the enzymes were obtained in the presence of more than 0.2mM alpha-D
      glucose 1,6-bisphosphate. Although both enzymes were attached to the alpha
      phosphohexomutase superfamily, amino acid sequence homology between TgPGM-I and
      TgPGM-II showed very low overall identity (25%). No alpha-phosphomannomutase (EC
      5.4.2.8) activity was detected for either enzyme. The data indicated that TgPGM
      I, but not TgPGM-II, may play an important role in alpha-D-glucose 6-phosphate
      production.

PMID- 20153839
TI  - Limited cholesterol depletion causes aggregation of plasma membrane lipid rafts
      inducing T cell activation.
AB  - Acute cholesterol depletion is generally associated with decreased or abolished T
      cell signalling but it can also cause T cell activation. This anomaly has been
      addressed in Jurkat T cells using progressive cholesterol depletion with methyl
      beta-cyclodextrin (MBCD). At depletion levels higher than 50% there is
      substantial cell death, which explains reports of signalling inhibition. At 10
      20% depletion levels, tyrosine phosphorylation is increased, ERK is activated and
      there is a small increase in cytoplasmic Ca(2+). Peripheral actin polymerisation
      is also triggered by limited cholesterol depletion. Strikingly, the lipid raft
      marker GM1 aggregates upon cholesterol depletion and these aggregated domains
      concentrate the signalling proteins Lck and LAT, whereas the opposite is true for
      the non lipid raft marker the transferrin receptor. Using PP2, an inhibitor of
      Src family kinase activation, it is demonstrated that the lipid raft aggregation
      occurs independently of and thus upstream of the signalling response. Upon
      cholesterol depletion there is an increase in overall plasma membrane order,
      indicative of more ordered domains forming at the expense of disordered domains.
      That cholesterol depletion and not unspecific effects of MBCD was behind the
      reported results was confirmed by performing all experiments with MBCD
      cholesterol, when no net cholesterol extraction took place. We conclude that non
      lethal cholesterol depletion causes the aggregation of lipid rafts which then
      induces T cell signalling.

PMID- 20153840
TI  - Apolipoprotein A-V associates with intrahepatic lipid droplets and influences
      triglyceride accumulation.
AB  - Apolipoprotein A-V (apoA-V), secreted solely by the liver, is a low abundance
      protein that strongly influences plasma triglyceride (TG) levels. In vitro, in
      transfected hepatoma cell lines apoA-V is largely retained within the cell in
      association with cytosolic lipid droplets (LD). To evaluate if this is true in
      vivo, in the present study the amount of apoA-V in the plasma compartment versus
      liver tissue was determined in APOA5 transgenic (Tg) mice. The majority of total
      apoA-V ( approximately 80%) was in the plasma compartment. Injection of APOA5 Tg
      mice with heparin increased plasma apoA-V protein levels by approximately 25%
      indicating the existence of a heparin-releasable pool. Intrahepatic apoA-V was
      associated with LD isolated from livers of wild type (WT) and APOA5 Tg mice.
      Furthermore, livers from APOA5 Tg mice contained significantly higher amounts of
      TG than livers from WT or apoa5 knockout mice suggesting that apoA-V influences
      intrahepatic TG levels.

PMID- 20153841
TI  - First cleavages, preblastula and blastula in the parthenogenetic mite
      Archegozetes longisetosus (Acari, Oribatida) indicate holoblastic rather than
      superficial cleavage.
AB  - The mode of cleavage in the Acari is generalized as superficial or intralecithal,
      with a preceding phase of total (holoblastic) cleavage, but the knowledge is
      fragmentary and conclusions have been inconsistent, even when relating to the
      same species. Since no data about early embryology is available for the speciose
      group Oribatida, we studied Archegozetes longisetosus using transmission electron
      microscopy. We focused on early cleavages and the formation of the blastula, as
      these are the important and controversial points in early embryology of the
      Acari. We expected, as postulated for other acarine eggs, the early cleavages to
      be holoblastic and followed by a superficial preblastoderm stage. The early
      cleavages of A. longisetosus are holoblastic and blastomeres give rise to yolk
      free micromeres and macromeres containing all the yolk. In contrast to
      expectations, the micromeres do not form a superficial preblastoderm layer. They
      are scattered along the embryonic surface and form an external, monocellular
      layer that covers the whole surface of the embryo. Since each of the existing TEM
      studies of mites shows this same pattern, and since this specialized form of
      total cleavage seems to be unique in Chelicerata, it may be the general mode of
      cleavage in Acari. However, the question will require much more investigation,
      especially since most data relate to the Actinotrichida and very few are
      currently available for species in the other major group, the Anactinotrichida.

PMID- 20153842
TI  - Expression of two novel transcripts in the mouse definitive endoderm.
AB  - Here we describe the expression of two novel transcripts, Ende (AK014119) and Npe
      (AK084355), during early mouse embryogenesis. Ende mRNA was first detected at
      embryonic day (E) 7.0 in a small population of epiblast cells in the distal half
      of the embryo. At E7.5, Ende was expressed by newly formed definitive endoderm
      cells in the proximal half of the embryo, and was not expressed in extra
      embryonic endoderm. This expression pattern then changed to the ventral aspect of
      the developing foregut pocket and the entire hindgut pocket at E8.0-8.5, before
      becoming restricted to the foregut overlying the heart and the posterior-most
      hindgut. By E9.25 Ende expression was also observed in the posterior half of the
      ventral neural tube. Thus, Ende was expressed dynamically and in specific
      populations of the definitive endoderm from E7.0 to E8.5. We found Npe expression
      to be restricted to the node/posterior notochord region at the distal tip of the
      embryo between E7.0 and E8.0. By E9.5, Npe expression was observed in the
      posterior-most population of dorsal hindgut cells and notochord cells. Given
      their expression in mouse definitive endoderm populations, Ende and Npe will be
      valuable tools to study formation and development of this tissue.

PMID- 20153843
TI  - The fixed structure of Licochalcone A by alpha, beta-unsaturated ketone is
      necessary for anti-inflammatory activity through the inhibition of NF-kappaB
      activation.
AB  - Glycyrrhiza inflata has been used as a traditional medicine with anti
      inflammatory activity. Previously, we reported that a major component,
      Licochalcone A, potently inhibited TNFalpha-induced NF-kappaB activation by
      inhibiting IKKbeta activation. In this study, we investigated whether the fixed
      structure of Licochalcone A by alpha, beta-unsaturated ketone is required for its
      inhibitory effect of NF-kappaB activation. Interestingly, reduced Licochalcone A,
      which lacks a double bond, failed to inhibit TNFalpha-induced NF-kappaB
      activation. Whereas Licochalcone A potently inhibited TNFalpha-induced IKK
      activation, IkappaBalpha degradation, nuclear localization of NF-kappaB and its
      DNA binding activity, no inhibitory effect was observed by reduced Licochalcone
      A. In addition, TNFalpha-induced expression of inflammatory cytokines, CCL2/MCP-1
      and CXCL1/KC, was clearly inhibited by Licochalcone A but not reduced
      Licochalcone A. As a result, culture media pretreated with Licochalcone A but not
      reduced Licochalcone A following TNFalpha stimulation significantly inhibited the
      chemotactic activity of neutrophils. Furthermore, acute carrageenan-induced paw
      edema in mice was markedly inhibited by administration of Licochalcone A but not
      reduced Licochalcone A. Taken together, it is suggested that Licochalcone A is a
      promising anti-inflammatory drug in vivo and its fixed structure is critical for
      anti-inflammatory activity.

PMID- 20153845
TI  - Strategies towards high-quality binary protein interactome maps.
AB  - Many processes in a cell depend on protein-protein interactions (PPIs) and
      perturbations of these interactions can lead to diseases. Comprehensive knowledge
      of PPI networks will not only give us information on how the cell is organized,
      but will also provide new drug targets. Current binary PPI networks are mainly
      generated by high-throughput yeast two-hybrid. Due to the small overlap of these
      maps, it has long been assumed that these maps are of low quality containing many
      false positives. However, by using an orthogonal two-hybrid method, MAPPIT
      (mammalian protein-protein interaction trap), these maps were shown to be of high
      quality suggesting that the limited overlap is likely due to low sensitivity and
      not to low specificity.

PMID- 20153844
TI  - Chronic intermittent hypoxia augments chemoreflex control of sympathetic
      activity: role of the angiotensin II type 1 receptor.
AB  - Chronic exposure to intermittent hypoxia (CIH) increases carotid sinus nerve
      activity in normoxia and in response to acute hypoxia. We hypothesized that CIH
      augments basal and chemoreflex-stimulated sympathetic outflow through an
      angiotensin receptor-dependent mechanism. Rats were exposed to CIH for 28 days: a
      subset was treated with losartan. Then, lumbar sympathetic activity was recorded
      under anesthesia during 20-s apneas, isocapnic hypoxia, and potassium cyanide. We
      measured carotid body superoxide production and expression of angiotensin II type
      1 receptor, neuronal nitric oxide synthase, and NADPH oxidase. Sympathetic
      activity was higher in CIH vs. control rats at baseline, during apneas and
      isocapnic hypoxia, but not cyanide. Carotid body superoxide production and
      expression of angiotensin II type 1 receptor and gp91(phox) subunit of NADPH
      oxidase were elevated in CIH rats, whereas expression of neuronal nitric oxide
      synthase was reduced. None of these differences were evident in animals treated
      with losartan. CIH-induced augmentation of chemoreflex sensitivity occurs, at
      least in part, via the renin-angiotensin system.

PMID- 20153846
TI  - DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase
      extraction of young adult versus aged gastrocnemius tissue.
AB  - Contractile weakness and loss of muscle mass are critical features of the aging
      process in mammalians. Age-related fibre wasting has a profound effect on muscle
      metabolism, fibre type distribution and the overall physiological integrity of
      the neuromuscular system. This study has used mass spectrometry-based proteomics
      to investigate the fate of the aging rat muscle proteome. Using nonionic
      detergent phase extraction, this report shows that the aged gastrocnemius muscle
      exhibits a generally perturbed protein expression pattern in both the detergent
      extracted fraction and the aqueous protein complement from senescent muscle
      tissue. In the detergent-extracted fraction, the expression of ATP synthase,
      isocitrate dehydrogenase, enolase, tropomyosin and beta-actin was increased.
      Different isoforms of creatine kinase and prohibitin showed differential changes.
      In the aqueous fraction, malate dehydrogenase, sulfotransferase, triosephosphate
      isomerase, aldolase, cofilin-2 and lactate dehydrogenase showed increased levels.
      Interestingly, differential effects on dissimilar 2-D spots of the same protein
      species were shown for Cu/Zn superoxide dismutase, albumin, annexin A4 and
      phosphoglycolate phosphatase. Mitochondrial Hsp60, Hsp71 and nucleoside
      diphosphate kinase B exhibited a reduced abundance in aged muscle. The majority
      of altered proteins were found to be involved in mitochondrial metabolism,
      glycolysis, metabolic transportation, regulatory processes, the cellular stress
      response, detoxification mechanisms and muscle contraction.

PMID- 20153847
TI  - Response of Pseudomonas putida KT2440 to phenol at the level of membrane
      proteome.
AB  - This study led to the extension and refinement of our current model for the
      global response of Pseudomonas putida KT2440 to phenol by getting insights into
      the adaptive response mechanisms involving the membrane proteome. A two
      dimensional gel electrophoresis based protocol was optimized to allow the
      quantitative comparison of membrane proteins, by combining inner and outer
      membrane fractionation with membrane protein solubilization using the detergent
      dodecylmaltoside. Following phenol exposure, a coordinate increased content of
      protein subunits of known or putative solvent efflux pump systems (e.g. TtgA,
      TtgC, Ttg2A, Ttg2C, and PP_1516-7) and a decreased content of porins OprB, OprF,
      OprG and OprQ was registered, consistent with an adaptive response to reduce
      phenol intracellular concentration. This adaptive response may in part be
      mediated by post-translational modifications, as suggested by the relative
      content of the multiple forms identified for a few porins and efflux pump
      subunits. Results also suggest the important role of protein chaperones, of cell
      envelope and cell surface and of a more active respiratory chain in the response
      to phenol. All these mechanistic insights may be extended to Pseudomonas
      adaptation to solvents, of possible impact in biodegradation, bioremediation and
      biocatalysis.

PMID- 20153848
TI  - A new chemical approach to differentiate carboxy terminal peptide fragments in
      cyanogen bromide digests of proteins.
AB  - We present a novel approach to perform C-terminal sequence analysis by
      discriminating the C-terminal peptide in a mass spectral analysis of a CNBr
      digest. During CNBr cleavage, all Met-Xxx peptide bonds are cleaved and the
      generated internal peptides all end with a homoserine lactone (hsl)-derivative.
      The partial opening of the hsl-derivatives, by using a slightly basic buffer
      solution, results in the formation of m/z doublets (Deltam=18 Da) for all
      internal peptides and allows to identify the C-terminal peptide which appears as
      a singlet in the mass spectra. Using two model proteins we demonstrate that this
      approach can be applied to study proteins purified in gel or in solution. The
      chemical opening of the hsl-derivative does not require any sample clean-up and
      therefore, the sensitivity of the C-terminal sequencing approach is increased
      significantly. Finally, the new protocol was applied to characterize the C
      terminal sequence of two recombinant proteins. Tandem mass spectrometry by MALDI
      TOF/TOF allowed to identify the sequence of the C-terminal peptides. This novel
      approach will allow to perform a proteome-wide study of C-terminal proteolytic
      processing events in a high-throughput fashion.

PMID- 20153849
TI  - Cell-mediated BMP-2 liberation promotes bone formation in a mechanically unstable
      implant environment.
AB  - The flexible alloplastic materials that are used in bone-reconstruction surgery
      lack the mechanical stability that is necessary for sustained bone formation,
      even if this process is promoted by the application of an osteogenic agent, such
      as BMP-2. We hypothesize that if BMP-2 is delivered gradually, in a cell-mediated
      manner, to the surgical site, then the scaffolding material's lack of mechanical
      stability becomes a matter of indifference. Flexible discs of Ethisorb were
      functionalized with BMP-2, which was either adsorbed directly onto the material
      (rapid release kinetics) or incorporated into a calcium-phosphate coating (slow
      release kinetics). Unstabilized and titanium-plate-stabilized samples were
      implanted subcutaneously in rats and retrieved up to 14 days later for a
      histomorphometric analysis of bone and cartilage volumes. On day 14, the bone
      volume associated with titanium-plate-stabilized discs bearing an adsorbed depot
      of BMP-2 was 10-fold higher than that associated with their mechanically
      unstabilized counterparts. The bone volume associated with discs bearing a
      coating-incorporated depot of BMP-2 was similar in the mechanically unstabilized
      and titanium-plate-stabilized groups, and comparable to that associated with the
      titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2. Hence, if an
      osteogenic agent is delivered in a cell-mediated manner (via coating
      degradation), ossification can be promoted even within a mechanically unstable
      environment.

PMID- 20153850
TI  - Repair of a segmental long bone defect in human by implantation of a novel
      multiple disc graft.
AB  - Large segmental defects of the weight bearing long bones are very difficult to
      reconstruct. Current treatment options are afflicted with several limitations and
      disadvantages. We describe a novel approach to regenerate a segmental long bone
      defect in a patient using a multiple disc graft. Decellularized bovine trabecular
      bone discs were seeded with autologous bone marrow cells and cultured in a
      perfusion chamber for three weeks. Multiple cell-seeded discs were implanted to
      close a 72 mm defect of the distal tibia in a 58-year-old woman, and fixed by an
      intramedullary nail. Bone formation was assessed non-invasively by plain
      radiographs and 18F-labeled sodium fluoride-based co-registration of positron
      emission- and computed tomography (PET/CT). Bone was actively formed around the
      grafted defect as early as six weeks after surgery. Because the tibia was
      sufficiently stabilized, the patient was able to freely walk with full weight
      bearing 6 weeks after surgery. The uneventful two-year follow-up and the
      satisfaction of the patient demonstrated the success of the procedure. Therefore
      the use of multiple cell-seeded disc grafts can be considered as a treatment
      alternative for patients with segmental long bone defects.

PMID- 20153851
TI  - 17beta-Estradiol accentuates contractility of rat genioglossal muscle via
      regulation of estrogen receptor alpha.
AB  - OBJECTIVE: This study in rat genioglossus muscle (GG) was designed to test the
      hypothesis that the effects of estrogen are at least in part, meditated directly
      by the estrogen receptors (ERs) of muscle. DESIGN: Eighty-eight-week-old female
      Sprague-Dawley rats were randomly assigned to five groups: (1) normal animals
      (Normal); (2) sham operation animals (Sham); (3) ovariectomized animals without
      estrogen replacement (OVX); (4) ovariectomized animals with olive oil replacement
      (OVX+O); (5) ovariectomized animals with 17beta-estradiol replacement (OVX+E2).
      Six weeks later, GG was assessed in vivo for contractile properties and further
      analysis for ERs expression was carried out including real-time quantitative RT
      PCR, immunohistochemistry and Western blotting. RESULTS: The maximal twitch
      tension, 70%-decay time and fatigue index of GG decreased significantly in OVX
      group when compared with Normal group (P<0.05, P<0.05, P<0.05). However, all the
      three parameters reversed in OVX+E2 group especially fatigue index. Further
      analysis showed a clear expression of ERalpha and ERbeta in rat GG. The
      expression of both ERalpha protein and ERalpha mRNA was both significantly
      decreased in OVX group (P<0.05) and recovered back to previous level after
      receiving 17beta-estradiol replacement (P<0.05). But neither ERbeta protein nor
      ERbeta mRNA was regulated by estrogen deprivation and replacement. CONCLUSION:
      The results demonstrated that the contractility of GG was accentuated by
      estrogen. Moreover, these effects were at least in part, meditated directly via
      regulation of the expression of ERalpha. It might contribute to the protective
      effects of estrogen on the patency of upper airway and the pathogenesis of
      obstructive sleep apnea hypopnoea syndrome.

PMID- 20153852
TI  - Structure and solution properties of enzymatically synthesized glycogen.
AB  - Recently, a new enzymatic process for glycogen production was developed. In this
      process, short-chain amylose is used as a substrate for branching enzymes (BE, EC
      2.4.1.18). The molecular weight of the enzymatically synthesized glycogen (ESG)
      depends on the size and concentration of the substrate. Structural and
      physicochemical properties of ESG were compared to those of natural source
      glycogen (NSG). The average chain length, interior chain length, and exterior
      chain length of ESG were 8.2-11.6, 2.0-3.3, and 4.2-7.6, respectively. These
      values were within the range of variation of NSG. The appearances of both ESG and
      NSG in solution were opalescent (milky white and slightly bluish). Furthermore,
      transmission electron microscopy and atomic force microscopy showed that ESG
      molecules formed spherical particles, and that there were no differences between
      ESG and NSG. Viscometric analyses also showed the spherical nature of both
      glycogens. When ESG and NSG were treated with pullulanase, a glucan-hydrolyzing
      enzyme known to degrade glycogen only on its surface portion, both glycogens were
      similarly degraded. These analyses revealed that ESG shares similar molecular
      shapes and surface properties with NSG.

PMID- 20153853
TI  - Circulating maternal testosterone concentrations at 18 weeks of gestation predict
      circulating levels of antimullerian hormone in adolescence: a prospective cohort
      study.
AB  - This prospective study was established to determine the impact of maternal
      circulating androgen levels during normal pregnancy on ovarian function, as
      determined by early follicular phase antimullerian hormone (AMH) levels, inhibin
      B levels, and antral follicle count (AFC) in 244 female offspring in adolescence.
      Maternal circulating total testosterone levels at 18 weeks' gestation were
      statistically significantly correlated with early follicular-phase circulating
      AMH levels in female adolescent offspring, but no other statistically significant
      correlations were determined among the maternal androgens at 18 or 34 weeks of
      gestation and the markers of adolescent ovarian function.

PMID- 20153854
TI  - Decrease of mitochondrial DNA level in sperm from patients infected with human
      immunodeficiency virus-1 linked to nucleoside analogue reverse transcriptase
      inhibitors.
AB  - OBJECTIVE: To study sperm parameters in patients infected with human
      immunodeficiency virus (HIV)-1 and to analyze mitochondrial DNA (mtDNA) in sperm
      according to the HIV treatment. DESIGN: Observational study. SETTING: University
      affiliated teaching hospital. PATIENT(S): Thirty-two patients infected with HIV-1
      and 31 noninfected healthy men provided semen samples. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): After DNA extraction, mtDNA level was assessed using
      real-time polymerase chain reaction (PCR) (LightCycler) in whole semen and in
      selected spermatozoa from 90% density centrifugation gradients. For each sample,
      mtDNA and beta-globin gene sequences were amplified and PCR products were
      quantified. The mtDNA-to-beta-globin ratio expressed the number of mtDNA copies
      per cell. RESULT(S): Compared with the control group, several sperm parameters
      were altered in patients with HIV. The number of mtDNA copies per cell in whole
      semen was increased in HIV-infected patients (6.3+/-6.3 vs. 3.5+/-3.2). However,
      there was no statistically significant difference in mtDNA copy number in the
      spermatozoa obtained after density gradient centrifugation. The number of
      nucleoside analogue reverse transcriptase inhibitors (NRTI) taken by patients
      during treatment significantly influenced the mtDNA level in sperm (1 NRTI 7.6+/
      8.1, 2 NRTIs 7.0+/-5.1, 3 NRTIs 3.2+/-2.1). CONCLUSION(S): Using a specific
      method to measure sperm mtDNA, we demonstrated a decrease of mtDNA copies in
      spermatozoa after use of NRTIs with known mitochondrial toxicity.

PMID- 20153855
TI  - Detection of enlarged yolk sac on early ultrasound is associated with adverse
      pregnancy outcomes.
AB  - Pregnancies with mean yolk sac diameter>or=5 mm on early ultrasound require
      monitoring and counseling about a threefold increased risk for first-trimester
      loss independent of maternal risk factors such as age, body mass index,
      polycystic ovary syndrome, smoking, and diabetes. In addition, our study shows
      for the first time that enlarged yolk sac diameter may be associated with an
      increased risk of preterm delivery.

PMID- 20153856
TI  - Fertility preservation following torsion and severe ischemic injury of a solitary
      testis.
AB  - OBJECTIVE: To present a case of solitary testicular torsion and an adolescent
      faced with future hypogonadism and infertility. DESIGN: Case report. SETTING:
      University-affiliated teaching hospital. PATIENT(S): A 16-year-old male with
      solitary testicular torsion of >8 hours' duration. INTERVENTION(S): Immediate
      scrotal exploration, orchiopexy, and sperm cryopreservation. MAIN OUTCOME
      MEASURE(S): Maintenance of testosterone production and determination of
      preservation after detorsion of an ischemic testis. RESULT(S): Color flow Doppler
      ultrasound showed markedly decreased flow to solitary testis. A subjectively dead
      testis was seen upon scrotal exploration, with the decision to proceed with
      orchiopexy. Semen analysis of cryopreserved specimen 50 hours after onset of
      symptoms showed 1.4 mL, normal sperm concentration (89 million/mL), 67% motility,
      and 28% World Health Organization morphology. Normal levels of testosterone were
      found at 4 and 12 weeks after surgery. Testicular salvage with normal
      intratesticular blood flow was seen by ultrasound at 4 and 12 weeks after
      surgery. CONCLUSION(S): To our knowledge, this is the first reported case of
      testicular salvage after torsion of a solitary testicle with subsequent normal
      semen analysis and cryopreservation. This demonstrates the need to attempt
      salvage even in cases of subjectively dead testicle and the importance of
      offering expedient sperm cryopreservation in such cases.

PMID- 20153857
TI  - Triage during the week of the Sichuan earthquake: a review of utilized patient
      triage, care, and disposition procedures.
AB  - OBJECTIVES: There exists no standard hospital emergency department (ED) triage
      procedure model for earthquake victims. This study provides an overview of the
      hospital triage procedure used for patients evaluated and treated at the West
      China Hospital of Sichuan University, Chengdu in the Sichuan province of China,
      following the May 12, 2008 Wenchuan earthquake. METHODS: Emergency triage and
      treatment teams were comprised of senior emergency medicine (EM) attending
      physician, junior EM attending physician, EM residents, and specialty surgeons.
      Retrospective analysis of the hospital medical records of 2283 earthquake victims
      was performed. Victims' demographic data, triage process and group assignments,
      diagnoses and dispositions were reviewed. RESULTS: In the 2 weeks following the
      Wenchuan earthquake, 2283 total patients with earthquake-related injuries were
      admitted to our hospital. 54 victims (2.4%) were lost to follow up. Patients were
      triaged into four main groups: resuscitation (n=6), urgent treatment (n=369),
      delayed treatment (n=1502), and minor injuries (n=406). 68.9% (1572/2283) of the
      patients were admitted to the hospital during the 15 days after the earthquake.
      The overall hospital mortality rate was 1.0% (15/1572). 1304 victims were
      transferred to nearby hospitals after initial treatment, stabilization, or
      surgery. CONCLUSIONS: Proper triage strategy should be established prior to the
      onset of a mass casualty event and should be appropriate to both the severity of
      the disaster and the accepting facility resource availability. Triage methods
      utilizing multi-specialty treatment teams and dynamic hospital-wide coordination
      are critical for efficient, efficacious patient management. Hopefully, sharing
      with the emergency medicine community the arduous challenges we faced in the wake
      of the Wenchuan earthquake will be useful for planning the response to future
      disasters.

PMID- 20153858
TI  - High-intensity focused ultrasound treatment for non-neoplastic epithelial
      disorders of the vulva.
AB  - OBJECTIVE: To assess the efficacy of high-intensity focused ultrasound (HIFU)
      treatment in patients with non-neoplastic epithelial disorders of the vulva.
      METHOD: We reviewed 41 cases of lichen sclerosus, 38 cases of squamous cell
      hyperplasia, and 17 mixed cases treated by HIFU from April 2004 to July 2008 at
      the Women's Hospital of Zhejiang University School of Medicine. Biopsy specimens
      were assessed with light microscopy before and after treatment. RESULTS: Pruritus
      and signs of vulvar lesions were dramatically improved following HIFU treatment,
      without severe complications, and 90.23% of the patients were cured or had their
      symptoms improved 6months after treatment. On light microscopy, pigmentation and
      epithelial structures were recovered and dermal lymphocytic infiltration was
      reduced. The response rates were lower and complication rates higher among lichen
      sclerosus than among squamous cell hyperplasia cases (P<0.05 for both).
      CONCLUSION: Treatment with HIFU may be safe and effective in cases of vulvar
      dystrophy.

PMID- 20153859
TI  - Variability of residual platelet function despite clopidogrel treatment in
      patients with peripheral arterial occlusive disease.
AB  - Residual platelet function despite treatment with clopidogrel may predict an
      unfavourable cardiovascular outcome. The majority of studies have investigated
      the effects of clopidogrel administration in conjunction with aspirin in patients
      undergoing percutaneous coronary intervention. The primary objective of the
      present study was to assess the platelet response to clopidogrel in the absence
      of aspirin in patients with peripheral arterial occlusive disease (PAOD) and to
      investigate whether non-responsiveness to clopidogrel is reproducible during long
      term follow-up. Fifty-four clinically stable PAOD patients on a maintenance dose
      of 75 mg/d clopidogrel were enrolled in this study. Platelet function was
      assessed at baseline and after a median follow-up of 18 months using light
      transmittance aggregometry (LTA) with 2 microM ADP as an agonist. HPLC-coupled
      mass spectrometry was used to detect clopidogrel and clopidogrel carboxylic acid,
      the main metabolite of clopidogrel. Residual platelet function, as defined by
      late aggregation values within the reference range (i.e., >43%), was observed in
      35.2% of patients at baseline and 17.6% during follow-up. During the observation
      period, 26.5% had switched from responder to non-responder status or vice versa.
      Among non-responders, either clopidogrel or its metabolite was detected in 89.5%
      and 83.3% of patients at baseline and at follow-up, respectively. We conclude
      that non-responsiveness to clopidogrel as determined by ADP-induced LTA is not
      stable over time. This phenomenon cannot be attributed to non-compliance alone.

PMID- 20153860
TI  - Quantitative assessment of moisture damage for cacao bean quality using two
      dimensional gas chromatography combined with time-of-flight mass spectrometry and
      chemometrics.
AB  - Quality control of cacao beans is a significant issue in the chocolate industry.
      In this report, we describe how moisture damage to cacao beans alters the
      volatile chemical signature of the beans in a way that can be tracked
      quantitatively over time. The chemical signature of the beans is monitored via
      sampling the headspace of the vapor above a given bean sample. Headspace vapor
      sampled with solid-phase micro-extraction (SPME) was detected and analyzed with
      comprehensive two-dimensional gas chromatography combined with time-of-flight
      mass spectrometry (GCxGC-TOFMS). Cacao beans from six geographical origins (Costa
      Rica, Ghana, Ivory Coast, Venezuela, Ecuador, and Panama) were analyzed. Twenty
      nine analytes that change in concentration levels via the time-dependent moisture
      damage process were measured using chemometric software. Biomarker analytes that
      were independent of geographical origin were found. Furthermore, prediction
      algorithms were used to demonstrate that moisture damage could be verified before
      there were visible signs of mold by analyzing subsets of the 29 analytes. Thus, a
      quantitative approach to quality screening related to the identification of
      moisture damage in the absence of visible mold is presented.

PMID- 20153861
TI  - A novel TiO2 nanotube array/Ti wire incorporated solid-phase microextraction
      fiber with high strength, efficiency and selectivity.
AB  - A novel solid-phase microextraction (SPME) fiber is fabricated through the
      anodization of Ti wire substrates in an electrolyte containing ethylene glycol
      and NH(4)F. By a combination of field emission scanning electron microscope and X
      ray photoelectron spectroscope studies, it is shown that perpendicularly
      orientated and well-aligned TiO(2) nanotubes are grown in situ on the Ti wire
      substrate. The SPME fiber coupled with gas chromatograph (GC) is then used to
      extract polycyclic aromatic hydrocarbons (PAHs), anilines, phenols, and alkanes
      from standard and real water samples, and exhibits high selectivity for PAHs.
      After the optimization of adsorption factors (pH, ionic strength, time and
      temperature) and desorption factors (time and temperature) of the SPME fiber for
      PAHs, the limit of detection (LOD) of less than 0.1 microg L(-1) is achieved, and
      the calibration curves are all linear (R(2)> or =0.9898) in the range from 0.1 to
      1000 microg L(-1). Beyond that, the SPME fiber has high strength, large surface
      area, good stability at high temperature and in acid and alkali solutions, and
      long service life, making it have strong application potentials in the selective
      extraction of PAHs from complex samples at trace levels.

PMID- 20153862
TI  - Steady viscoelastic fluid flow between parallel plates under electro-osmotic
      forces: Phan-Thien-Tanner model.
AB  - The electro-osmotic flow of a viscoelastic fluid between parallel plates is
      investigated analytically. The rheology of the fluid is described by the Phan
      Thien-Tanner model. This model uses the Gordon-Schowalter convected derivative,
      which leads to a non-zero second normal stress difference in pure shear flow. A
      nonlinear Poisson-Boltzmann equation governing the electrical double-layer field
      and a body force generated by the applied electrical potential field are included
      in the analysis. Results are presented for the velocity and stress component
      profiles in the microchannel for different parametric values that characterize
      this flow. Equations for the critical shear rates and maximum electrical
      potential that can be applied to maintain a steady fully developed flow are
      derived and discussed.

PMID- 20153863
TI  - Adsorption of Pd(II) complexes from chloride solutions obtained by leaching
      chlorinated spent automotive catalysts on ion exchange resin Diaion WA21J.
AB  - It was found that Rh, Pd and Pt contained in the spent ceramic automotive
      catalysts could be effectively extracted by dry chlorination with chlorine. In
      order to concentrate Pd(II) contained in the chloride solution obtained from the
      dry chlorination process, thermodynamic and kinetics studies for adsorption of
      Pd(II) complexes from the chloride solutions on anionic exchange resin Diaion
      WA21J were carried out. It was found that Pd, Pt, Rh, Al, Fe, Si, Zn and Pb from
      the chloride solution could be adsorbed on the resin. The isothermal adsorption
      of Pd(II) was found to fit Freundlich, Langmuir and Dubinin-Kaganer-Radushkevich
      models under the adsorption conditions. The adsorption of Pd(II) on the resin was
      favorable according to the values of 1/n and R(L) from Freundlich and Langmuir
      adsorption isotherms, respectively. The maximum monolayer adsorption capacities
      Q(max) based on Langmuir adsorption isotherms were 5.70, 4.84 and 4.05 mg/g and
      the corresponding value X(m) based on Dubinin-Kaganer-Radushkevich were 5.55,
      4.69 and 4.01 mg/g at temperatures 18 degrees C, 28 degrees C and 40 degrees C,
      respectively. The apparent adsorption energies (E(ad)) based on Dubinin-Kaganer
      Radushkevich isotherm were -15.43, -16.22 and -23.57 kJ/mol for the temperatures
      18 degrees C, 28 degrees C and 40 degrees C, respectively. Chemical adsorption
      was a main mechanism involved in the adsorption process. Pd(II) adsorption on the
      resin could be accelerated by increasing the adsorption temperature. The
      adsorption of Pd(II) from the chloride solution on the resin underwent pseudo
      first order kinetic process and the apparent adsorption activation energy E(a)
      was 15.0 kJ/mol. The intra-particle diffusion was a main rate controlling step in
      the Pd(II) adsorption process under the adsorption conditions.

PMID- 20153864
TI  - Severe renal failure in a dog resembling human focal segmental
      glomerulosclerosis.
AB  - A case of renal disease in a dog resembling human focal segmental
      glomerulosclerosis is presented. A kidney biopsy from this animal showed focal
      glomerular sclerosis, with variable distribution, affecting the perihilar and
      peripheral segments of the glomerular tuft. Non-sclerotic glomeruli were markedly
      enlarged. Interstitial fibrosis in association with tubular atrophy affected
      approximately 20% of the area of the biopsy. Immunofluorescence labelling showed
      immunoglobulin M deposits entrapped in segmental sclerotic areas and
      ultrastructural examination revealed segmental sclerosis and obliteration of
      capillaries, vacuolation of podocytes and diffuse effacement of foot processes.
      The dog was humanely destroyed 1 month later. At necropsy examination there was
      severe end-stage kidney disease with interstitial fibrosis involving more than
      60% of the renal tissue. The clinical course and the microscopical,
      immunofluorescence and ultrastructural findings in this case have similarity to
      focal segmental glomerulosclerosis in man.

PMID- 20153865
TI  - Ovine heritable arthrogryposis multiplex congenita with probable lethal autosomal
      recessive mutation.
AB  - A novel congenital syndrome in lambs is described that is characterized by: (1)
      kyphoscoliosis (severe curvature, hunching and twisting of the thoracic spine,
      with associated abnormalities of the ribs and sternum), (2) distal arthrogryposis
      of the carpal and tarsal joints, and (3) cleft hard and soft palate or
      palatoschisis (a median fissure of the palate). Male and female lambs are
      affected equally and in multiple births there may be only one affected lamb. The
      affected lambs are born full term, but die shortly after birth because they are
      unable to start breathing. Affected lambs have slightly reduced bodyweight (due
      to low muscle mass) compared with normal newborn lambs of the same flock. The
      syndrome is remarkably similar to the recently described bovine heritable
      arthrogryposis multiplex congenita in the Angus breed. Genetic analysis of the
      flock by means of DNA microsatellite markers, together with study of the
      reproductive management of the flock, allowed us to discount an environmental
      aetiology (e.g. intoxications or infections). In contrast, evidence supports an
      autosomal recessive inherited disease for which the name ovine heritable
      arthrogryposis multiplex congenita is proposed.

PMID- 20153866
TI  - Disseminated infection with Mycobacterium genavense in a grizzled giant squirrel
      (Ratufa macroura) associated with the isolation of an unknown Mycobacterium.
AB  - Disseminated infection with Mycobacterium genavense was diagnosed in an adult
      grizzled giant squirrel (Ratufa macroura). Microscopical examination showed
      granulomatous inflammation in the brain, kidneys, lungs and maxilla with
      intracellular acid-fast bacilli. M. genavense and a novel species of
      Mycobacterium (proposed name 'Mycobacterium lipsiensis') were identified.

PMID- 20153867
TI  - Immunohistochemical expression of caveolin-1 in normal and neoplastic canine
      mammary tissue.
AB  - Caveolins are the major structural proteins of caveolae and play a role in tumour
      surveillance. The expression of caveolin-1 (Cav-1) was investigated
      immunohistochemically in samples of normal canine mammary tissue (n=5), benign
      (n=23) and malignant (n=45) mammary tumours, tumour emboli (n=10) and metastatic
      lesions (n=10). Cav-1 was not expressed by normal luminal epithelium, but was
      consistently expressed by normal myoepithelial cells. There was no epithelial
      expression of Cav-1 by the benign mammary lesions, but the molecule was detected
      in 35.6% of the malignant lesions, 80% of the tumour emboli and in 40% of the
      metastatic lesions. These findings link increased expression of Cav-1 to
      neoplastic transformation and suggest that Cav-1 expression is associated with
      more malignant canine mammary tumours and their vascular invasion and regional
      lymph node metastasis.

PMID- 20153868
TI  - Caveolin-1 in diagnosis and prognosis of canine mammary tumours: comparison of
      evaluation systems.
AB  - Caveolin-1 (Cav-1) is a major structural protein of caveolae, plasma membrane
      invaginations related to several cellular processes including regulation of
      signal transduction. In recent years there has been some controversy regarding
      the distribution of Cav-1 in normal and neoplastic mammary cell types, which may
      be attributed to different scoring systems adopted in different studies. The
      present study compares Cav-1 immunoexpression in normal (n=17) and neoplastic
      (n=79) canine mammary tissues assessed by two different scoring methods
      (previously reported by others with conflicting results) and associates Cav-1
      expression with metastasis and overall survival (OS). Results obtained with both
      scoring methods were similar, revealing absence of immunoreactivity in normal
      luminal epithelium and in benign neoplasms and clearly associating Cav-1
      expression with malignant transformation. The data suggest that Cav-1 expression
      is associated with highly malignant subtypes of mammary tumours (i.e. basal-like
      carcinoma), invasion and metastasis, thus supporting the hypothesis that it may
      play a major role in the epithelial-mesenchymal transition process. Furthermore,
      one of the scoring systems employed associated Cav-1 expression with unfavourable
      prognosis in canine mammary carcinomas, showing a strong correlation between Cav
      1-positive carcinomas and shorter OS.

PMID- 20153869
TI  - Atypical interstitial pneumonia in grazing adult red deer (Cervus elaphus).
AB  - A herd of red deer experienced a small outbreak of atypical interstitial
      pneumonia on two occasions 3 years apart. The first occasion involved the death
      of two of a group of 70 hinds and the second outbreak involved a single death in
      a similar sized group. On both occasions a number of the adults exhibited
      increased respiratory effort, particularly on exercise. Both outbreaks occurred
      in July, a few days after moving the herd from a close grazed grass paddock to an
      aftermath paddock, which had regrown to a good sward. The history and pathology
      is reminiscent of 3-methyl indole toxicity in cattle.

PMID- 20153870
TI  - Metastatic extra-adrenal sympathetic paraganglioma in a horse.
AB  - Post-mortem examination was performed on a horse that died after exhibiting signs
      of colic. Gross findings included haemoperitoneum and a large round encapsulated
      mass located in the sublumbar area cranial to the left kidney. On sectioning the
      mass was solid red to brown and small nodules of similar tissue were noted at the
      periphery of the mass. The spleen was firm and three nodules were found in one
      thyroid gland. Microscopically, the abdominal mass, adjacent nodules, the spleen
      and one thyroid nodule consisted of clusters and cords of round to oval
      neoplastic cells, separated by a fine collagen and reticulin fibre network.
      Immunohistochemically, tumour cells expressed chromogranin A, synaptophysin and
      neuron-specific enolase, but did not express cytokeratin. The findings were
      consistent with a metastatic extra-adrenal sympathetic paraganglioma.

PMID- 20153871
TI  - Borna disease in an adult alpaca stallion (Lama pacos).
AB  - Borna disease (BD) was diagnosed in a 2-year-old male alpaca with a history of
      chronic suppressed sexual desire and acute stretching convulsions. Microscopical
      examination of the central nervous system revealed non-purulent
      meningoencephalitis with mononuclear perivascular cuffing. The diagnosis was
      confirmed by immunohistochemistry, in-situ hybridization, polymerase chain
      reaction (PCR) and sequencing of PCR products and alignment with known Borna
      disease virus sequences. Serological screening of the herd was performed. This is
      the first detailed report of naturally occurring BD in alpacas.

PMID- 20153872
TI  - Posterior or lateral involvement in nonanterior wall infarction. What's in a
      name?

PMID- 20153873
TI  - How many leads through persistent left superior vein cava and coronary sinus?
AB  - In the modern implanting era with progressive expanding indications to
      resynchronization therapy, upgrading procedure is a relatively common event.
      Persistent left superior vena cava (PLSVC), the most common venous abnormality,
      may exacerbate technical difficulties. We describe the procedure of upgrading
      from a dual chamber pacemaker to resynchronization/defibrillation system with a
      total of 4 leads through a PLSVC entering a dilated coronary sinus (CS) never
      described before. The case report, in addition to the description of a unique
      technical approach, raises a lot of clinical questions about how many leads we
      can introduce in such a venous structure and inside CS without hemodynamic impact
      on venous drainage potentially leading to life-threatening situations.

PMID- 20153874
TI  - Insulin resistance and metabolic syndrome in patients with nonfunctioning adrenal
      incidentalomas: a cause-effect relationship?
AB  - The objective of the study was to assess insulin resistance (IR) and metabolic
      syndrome (MS) in patients with nonfunctioning adrenal incidentalomas (NFAIs).
      Among a total cohort of 46 patients with adrenal incidentalomas, we studied 29
      patients with NFAIs (mean age, 54 +/- 9 years; body mass index, 29 +/- 3 kg/m(2))
      and 37 age-, sex-, and body mass index-matched healthy controls. Besides the
      endocrine workup, IR was evaluated using fasting glucose and insulin
      concentrations, homeostasis model assessment of IR, and quantitative insulin
      sensitivity check index. In a subgroup of patients undergoing an oral glucose
      tolerance test, Matsuda index and total area under the curve for glucose and
      insulin were also evaluated. Total cholesterol, high-density lipoprotein, low
      density lipoprotein, triglycerides, and other biochemical parameters were
      measured with standard techniques. Body composition was determined with dual
      energy x-ray absorptiometry. Patients with NFAIs exhibited higher fasting
      glucose, insulin, and homeostasis model assessment of IR values; decreased
      quantitative insulin sensitivity check index and Matsuda index; and an increased
      although not statistically significant-area under the curve for glucose and
      insulin compared with controls (P < .05). In addition, they exhibited higher
      systolic and diastolic blood pressure, triglycerides, and gamma
      glutamyltransferase and lower high-density lipoprotein cholesterol levels
      compared with controls (P < .05). Patients with NFAIs were all obese with a
      central type of fat accumulation and increased appendicular lean mass. Indices of
      IR showed a positive correlation with indices of MS (P < .05), but no correlation
      with markers of hormonal activity. Nonfunctioning adrenal incidentalomas are
      characterized by IR, hypertension, dyslipidemia, and fatty liver disease, all of
      them being components of MS. Thus, patients with NFAIs should be screened for MS
      during their initial workup to identify those at cardiometabolic risk and
      implement the appropriate interventions.

PMID- 20153875
TI  - Influence of macronutrient intake and anthropometric characteristics on plasma
      insulin after eccentric exercise.
AB  - To increase understanding of the interaction between macronutrients and insulin
      resistance (IR), this study sought to determine the influence of macronutrient
      intake and anthropometric differences on IR and inflammation responses to
      eccentric resistance exercise. Men and women (n = 12, 19-36 years old)
      participated in a crossover study and completed 6 sets of 10 unilateral maximal
      eccentric contractions of the elbow flexors and extensors followed by controlled
      diet conditions for the first 8 hours postexercise of carbohydrate/fat/protein
      proportions of either 75%/15%/10% (CHO) or 6%/70%/24% (FAT/PRO). Fasting glucose,
      insulin, homeostatic model assessment (HOMA) variables, and interleukin (IL)
      1beta were measured preexercise and 23 hours postexercise (additional measures of
      glucose and insulin 1 hour after meals consumed 0.5, 3, and 7 hours
      postexercise). Insulin increased more (P < .01) in the CHO compared with the
      FAT/PRO condition at 1.5, 4, and 8 hours postexercise. Insulin, HOMA-IR, and HOMA
      beta-cell function increased 23 hours postexercise in both conditions, whereas IL
      1beta increased 23 hours postexercise only in the CHO condition. Magnitude of
      change (Delta) for these variables associated positively with body mass index
      (BMI) and waist to hip ratio (WHR) in the CHO and inversely in the FAT/PRO
      condition; that is, r = 0.53 (P = .10) and r = -0.82 (P < .01) for BMI vs Delta
      insulin in CHO and FAT/PRO conditions, respectively. The Delta IL-1beta
      associated with BMI (r = 0.62, P < .05) and WHR (r = 0.84, P < .01) in the CHO
      condition. The CHO enhanced IR and inflammation as BMI and WHR increased, whereas
      fat and protein enhanced IR as BMI and WHR decreased. Thus, BMI and WHR may need
      to be taken into account in the development of nutritional strategies to prevent
      IR.

PMID- 20153876
TI  - The effect of mixing two herbicides mesotrione and nicosulfuron on their
      photochemical reactivity on cuticular wax film.
AB  - There are growing concerns about the environmental impacts of pesticides with a
      consequent increasing demand for meaningful and accurate information on their
      consumption and use pattern. Pesticides reactivity towards light is rarely
      considered at the leaf surface after crop treatment although it is directly
      impacting the pesticide efficiency. We have established a test on thin wax films
      which mimic well the leaf surface. Under simulated solar light herbicides
      mesotrione and nicosulfuron as well as their mixture are photoreactive. For both
      herbicides considered separately, there is a strong accelerating effect of
      adjuvants compared to the pure active ingredient. Mesotrione, a triketonic
      herbicide was very reactive with a half-life of photolysis of 2h. Nicosulfuron, a
      sulfonylurea, has a half-life of photolysis of 32 h. The mixing of the two
      formulated herbicides had an accelerating effect on both herbicide decay rates.
      The products formed when considering the pure molecule were mainly the result of
      photohydrolysis, oxidation and cyclisation. While pesticide photostability on
      crops is not evaluated for registration, this study demonstrates that these
      photochemical tests could be useful to improve the pesticide effectiveness and
      reduce the applied dose.

PMID- 20153877
TI  - Oxidative stress responses of Daphnia magna exposed to TiO(2) nanoparticles
      according to size fraction.
AB  - Size is one of important factors determining titanium dioxide nanoparticle
      (TiO(2) NP) toxicity since penetration is eased with decreasing particle size and
      bioavailability is increased. The effect of particle size on oxidative stress
      against titanium dioxide nanoparticle (TiO(2) NP) exposure to Daphnia magna was
      investigated with both acute and chronic toxicity tests. Experiments on
      biochemical responses, repeatedly performed after size fractionation of the NPs
      using filtration, focused on the activities of four antioxidant enzymes: catalase
      (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione
      S-transferase (GST). In the chronic bioassay, the mortality was significantly
      increased at TiO(2) NP concentrations of 5 and 10mg/L; however, no reduction of
      the reproduction ability was observed. Biochemical measurements showed that
      TiO(2) NP exposure significantly increased the antioxidant enzyme activities in
      D. magna. CAT, GPX and GST, but not SOD, showed a concentration-dependent
      increase. In terms of size fraction, particles ranging from 400 to 800nm
      exhibited an increase of antioxidant enzyme activities in GST and GPX. These
      biochemical level observations suggested that TiO(2) NP toxicity was mediated by
      reactive oxygen species (ROS) generation via oxidative stress in D. magna. The
      increased mortality at the concentration of 5mg/L in the chronic bioassay was
      attributed to accumulated TiO(2) NPs in the intestine of D. magna, which might
      induce effects such as oxidative stress relating to the induction of antioxidant
      enzymes.

PMID- 20153878
TI  - Disposal of water treatment wastes containing arsenic - a review.
AB  - Solid waste management in developing countries is often unsustainable, relying on
      uncontrolled disposal in waste dumps. Particular problems arise from the disposal
      of treatment residues generated by removing arsenic (As) from drinking water
      because As can be highly mobile and has the potential to leach back to ground and
      surface waters. This paper reviews the disposal of water treatment wastes
      containing As, with a particular emphasis on stabilisation/solidification (S/S)
      technologies which are currently used to treat industrial wastes containing As.
      These have been assessed for their appropriateness for treating As containing
      water treatment wastes. Portland cement/lime mixes are expected (at least in
      part) to be appropriate for wastes from sorptive filters, but may not be
      appropriate for precipitative sludges, because ferric flocs often used to sorb As
      can retard cement hydration. Brine resulting from the regeneration of activated
      alumina filters is likely to accelerate cement hydration. Portland cement can
      immobilize soluble arsenites and has been successfully used to stabilise As-rich
      sludges and it may also be suitable for treating sludges generated from
      precipitative removal units. Oxidation of As(III) to As(V) and the formation of
      calcium-arsenic compounds are important immobilisation mechanisms for As in
      cements. Geopolymers are alternative binder systems that are effective for
      treating wastes rich in alumina and metal hydroxides and may have potential for
      As wastes generated using activated alumina. The long-term stability of cemented,
      arsenic-bearing wastes is however uncertain, as like many cements, they are
      susceptible to carbonation effects which may result in the subsequent re-release
      of As.

PMID- 20153879
TI  - Current status on tissue factor activation of factor VIIa.
AB  - Free factor VIIa displays a zymogen-like behavior with low intrinsic activity.
      Formation of a complex between factor VIIa and tissue factor is necessary to
      enhance the procoagulant activity of factor VIIa, not only by providing membrane
      localization, substrate exosites and positioning the active site at an
      appropriate distance above the surface but also by allosteric enhancement of the
      enzymatic activity, and this event signals initiation of blood coagulation. The
      interaction is of high affinity and all the domains are engaged at the interface.
      The crosstalk between the protease domain of factor VIIa, in particular residue
      Met-306, and the N-terminal domain of tissue factor provides the starting point
      for the allosteric activation of factor VIIa. The pathway(s) of conformational
      transitions in factor VIIa ensuing tissue factor binding has not been entirely
      mapped. The present paper is a brief compilation of our current knowledge of the
      allosteric mechanism by which tissue factor induces and stabilizes the active
      conformation of factor VIIa.

PMID- 20153880
TI  - Use of the Delphi method to facilitate antithrombotics prescription during
      pregnancy.
AB  - INTRODUCTION: Management of pregnant women at risk for venous thromboembolism
      (VTE) remains complex. Guidelines do not definitively fix optimal strategies due
      to limited trial data. Our objective was to build an easy-to-use tool allowing
      individualised, risk-adapted prophylaxis. MATERIALS AND METHODS: A Delphi
      exercise was conducted to collect 19 French experts' opinions on pregnancy
      related VTE. RESULTS: Experts with an active interest in clinical research and
      care of VTE and placental vascular complications were selected. The risk score
      was classified by an anonymous computer vote. A scoring system for VTE risk in
      pregnant women was developed, each score being associated with a specific
      treatment: graduated elastic compression stockings, aspirin, prophylactic Low
      Molecular Weight Heparin (LMWH: variable durations), or adjusted-dose of LMWH
      through pregnancy and postpartum. CONCLUSIONS: Our simple consensual scoring
      system offers an individual estimation of thrombosis risk during pregnancy
      together with its related therapeutic strategy, in accordance with most of the
      new international recommendations. The accuracy of our individual risk score
      based therapeutic guidance is currently being prospectively evaluated in a
      multicenter trial.

PMID- 20153881
TI  - Reduction in patient-reported acute morbidity in prostate cancer patients treated
      with 81-Gy Intensity-modulated radiotherapy using reduced planning target volume
      margins and electromagnetic tracking: assessing the impact of margin reduction
      study.
AB  - OBJECTIVE: To investigate whether patient-reported quality of life after high
      dose external beam intensity-modulated radiotherapy for prostate cancer can be
      improved by decreasing planning target volume margins while using real-time tumor
      tracking. METHODS: Study patients underwent radiotherapy with nominal 3-mm
      margins and electromagnetic real-time tracking. Morbidity was assessed before and
      at the end of radiotherapy using Expanded Prostate Cancer Index Composite (EPIC)
      questionnaires. Changes in scores were compared between the Assessing Impact of
      Margin Reduction (AIM) study cohort and the comparator Prostate Cancer Outcomes
      and Satisfaction with Treatment Quality Assessment (PROST-QA) cohort, treated
      with conventional margins. RESULTS: The 64 patients in the prospective AIM study
      had generally less favorable clinical characteristics than the 153 comparator
      patients. Study patients had similar or slightly poorer pretreatment EPIC scores
      than comparator patients in bowel, urinary, and sexual domains. AIM patients
      receiving radiotherapy had less bowel morbidity than the comparator group as
      measured by changes in mean bowel and/or rectal domain EPIC scores from
      pretreatment to 2 months after start of treatment (-1.5 vs -16.0, P = .001).
      Using a change in EPIC score >0.5 baseline standard deviation as the measure of
      clinical relevance, AIM study patients experienced meaningful decline in only 1
      health-related quality of life domain (urinary) whereas decline in 3 health
      related quality of life domains (urinary, sexual, and bowel/rectal) was observed
      in the PROST-QA comparator cohort. CONCLUSIONS: Prostate cancer patients treated
      with reduced margins and tumor tracking had less radiotherapy-related morbidity
      than their counterparts treated with conventional margins. Highly contoured
      intensity-modulated radiotherapy shows promise as a successful strategy for
      reducing morbidity in prostate cancer treatment.

PMID- 20153882
TI  - A new simple technique of laparoscopic temporary ovarian suspension in addition
      to ovarian cryopreservation for women prior to posterior pelvic radiation.

PMID- 20153883
TI  - Does the number of nodes removed impact survival in vulvar cancer patients with
      node-negative disease?
AB  - OBJECTIVE: To determine if the extent of lymphadenectomy as determined by lymph
      node count from an inguinal-femoral lymph node dissection for vulvar cancer
      impacts overall survival (OS) and disease-specific survival (DSS) in patients
      with node-negative disease. METHODS: Patients with stage I, II and III squamous
      cell carcinoma of the vulva who underwent primary inguinal-femoral nodal
      dissection were identified from the Surveillance, Epidemiology and End Results
      Program between 1988 and 2003. Patients were divided into 2 groups, those with
      <or=10 nodes and those with >10 nodes removed, and analyzed according to stage.
      All patients with histologically positive nodes were excluded. Log-rank test was
      done for univariate analysis. Cox regression method was used for multivariate
      analysis. RESULTS: Squamous cell vulvar cancer was identified in 1030 patients.
      Statistically significant differences were seen on univariate analysis of OS
      between stage II and III patients with <or=10 and >10 nodes removed. The
      difference in 5-year DSS survival was statistically significant only for patients
      with stage III disease. On multivariate analysis age, stage and number of lymph
      nodes removed were all found to be significant variables affecting OS and DSS.
      CONCLUSIONS: The removal of greater than 10 lymph nodes was associated with a
      significant improvement in DSS in patients with stage III vulvar carcinoma. This
      improvement in survival may be due to removal of micrometastatic disease in the
      inguinal lymph nodes. These data suggest that a thorough inguinal-femoral lymph
      node dissection should be performed in patients with advanced-stage node-negative
      vulvar carcinoma.

PMID- 20153884
TI  - Decreased severity of ovarian cancer and increased survival in hens fed a
      flaxseed-enriched diet for 1 year.
AB  - OBJECTIVE: With the exception of the laying hen, no other animal model of
      spontaneous ovarian surface epithelial cancer replicates the human disease.
      Flaxseed is the richest vegetable source of omega-3 fatty acids, which are
      chemopreventive in breast cancer and may be important in other cancers. The
      objective of this study was to determine if a flaxseed-enriched diet had a
      chemopreventive effect on ovarian cancer in the laying hen. METHODS: White
      Leghorn hens were fed with 10% flaxseed-enriched or standard diet for 1 year. The
      incidence and severity of ovarian cancer were determined by gross pathology and
      histology in the two groups. General health markers were also measured. Eggs were
      collected and analyzed by gas chromatography to determine omega-3 fatty acid
      levels. RESULTS: A significant reduction in late stage ovarian tumors was
      detected in the flaxseed-fed hens. Incidence rates of ovarian cancer were not
      significantly different between the two groups. The results indicate that a
      flaxseed diet increases overall survival in the laying hen. Flaxseed-fed hens'
      eggs incorporated significantly more omega-3 fatty acids compared to control
      hens. CONCLUSIONS: These findings show that 10% flaxseed supplementation for 1
      year in the laying hen results in a significant reduction in the severity of
      ovarian cancer, but no change in the incidence of the disease. Hens fed flaxseed
      had overall better health and reduced mortality. These findings may provide the
      basis for a clinical trial that evaluates the efficacy of flaxseed as a
      chemosuppressant of ovarian cancer in women.

PMID- 20153885
TI  - Mismatch repair status and outcomes after adjuvant therapy in patients with
      surgically staged endometrial cancer.
AB  - OBJECTIVES: To determine whether DNA mismatch repair (MMR) modifies the response
      to chemotherapy or radiotherapy in patients with endometrial cancer. METHODS:
      Immunohistochemistry (IHC) for the DNA MMR proteins MLH1, MSH2, MSH6, and PMS2
      was performed on a tissue microarray of specimens of primary endometrial cancer.
      MMR deficiency was defined as lack of expression of one or more proteins.
      Expression of all proteins classified a tumor as having an intact MMR system.
      Recurrence rates were calculated for women treated with platinum-based
      chemotherapy or pelvic external beam radiation. Comparisons were made using the
      log-rank test. Multiple comparisons were controlled for by utilizing the
      Bonferroni correction method. RESULTS: Four hundred seventy-seven cases of
      endometrial cancer were evaluated on a tissue microarray (TMA). One hundred fifty
      eight patients (41%) received chemotherapy. Sixty-six patients (17%) received
      pelvic teletherapy. Overall and progression-free survival were not different
      between patients whose tumors had intact MMR and those with defective MMR when
      stratified by adjuvant treatment with radiation or chemotherapy. Subgroup
      analyses stratified by histology (non-endometrioid versus endometrioid) and stage
      did show significant survival differences. There was a significant increase in
      overall (p=0.003) and progression-free (p=0.004) survival in those with MMR
      deficient, non-endometrioid tumors treated with teletherapy compared to those
      with an intact MMR system. Improved progression-free survival was noted in
      patients with intact MMR with stage III/IV disease treated with adjuvant
      chemotherapy (p=0.031). CONCLUSIONS: Subgroups of patients with non-endometrioid
      endometrial cancer and defective MMR may have improved survival after adjuvant
      radiotherapy. Patients with advanced stage endometrial cancer and defects in
      mismatch repair may receive less benefit from adjuvant chemotherapy.

PMID- 20153886
TI  - Survival outcomes for women undergoing type III robotic radical hysterectomy for
      cervical cancer: a 3-year experience.
AB  - OBJECTIVES.: To assess progression-free (PFS) and overall survival (OS) for women
      with cervical cancer who underwent type III robotic radical hysterectomy (RRH).
      METHODS.: A retrospective analysis of women who underwent RRH from 2005 to 2008
      was performed. The data analyzed included patient demographics, histology,
      clinical stage, surgical margins, lymph node and disease status. Comparison was
      made to a group of historical open radical hysterectomies. Survival statistics
      were analyzed using the Kaplan-Meier method. RESULTS.: Seventy-one women
      underwent attempted RRH during the study period. Eight were excluded from
      analysis, 4 for non-cervical primary and 4 cases aborted due to extent of
      disease. Squamous was the most common histology (62%) followed by adenocarcinoma
      (32%). Median patient age was 43 years. There was one intraoperative complication
      (asystole after induction) and two postoperative complications (ICU admission to
      rule out myocardial infarction and reoperation for cuff dehiscence). Of the
      patients who underwent RRH, 32% received whole-pelvis radiation with chemo
      sensitization. The median follow-up was 12.2 months (range 0.2-36.3 months).
      Kaplan-Meier survival analysis demonstrated 94% PFS and OS at 36 months due to
      the recurrence and death of one patient. Compared with a historical cohort at our
      institution, there was no statistically significant difference in PFS (P=0.27) or
      OS (P=0.47). CONCLUSIONS.: RRH is safe and feasible and has been shown to be
      associated with improved operative measures. This study shows that at 3 years,
      RRH appears to have PFS and OS equivalent to that of traditional laparotomy.
      Longer follow-up is needed, but early data are supportive of at least equivalent
      oncologic outcomes compared with other surgical modalities.

PMID- 20153887
TI  - Peripheral mechanisms for vocal production in birds - differences and
      similarities to human speech and singing.
AB  - Song production in songbirds is a model system for studying learned vocal
      behavior. As in humans, bird phonation involves three main motor systems
      (respiration, vocal organ and vocal tract). The avian respiratory mechanism uses
      pressure regulation in air sacs to ventilate a rigid lung. In songbirds sound is
      generated with two independently controlled sound sources, which reside in a
      uniquely avian vocal organ, the syrinx. However, the physical sound generation
      mechanism in the syrinx shows strong analogies to that in the human larynx, such
      that both can be characterized as myoelastic-aerodynamic sound sources.
      Similarities include active adduction and abduction, oscillating tissue masses
      which modulate flow rate through the organ and a layered structure of the
      oscillating tissue masses giving rise to complex viscoelastic properties.
      Differences in the functional morphology of the sound producing system between
      birds and humans require specific motor control patterns. The songbird vocal
      apparatus is adapted for high speed, suggesting that temporal patterns and fast
      modulation of sound features are important in acoustic communication. Rapid
      respiratory patterns determine the coarse temporal structure of song and maintain
      gas exchange even during very long songs. The respiratory system also contributes
      to the fine control of airflow. Muscular control of the vocal organ regulates
      airflow and acoustic features. The upper vocal tract of birds filters the sounds
      generated in the syrinx, and filter properties are actively adjusted. Nonlinear
      source-filter interactions may also play a role. The unique morphology and
      biomechanical system for sound production in birds presents an interesting model
      for exploring parallels in control mechanisms that give rise to highly convergent
      physical patterns of sound generation. More comparative work should provide a
      rich source for our understanding of the evolution of complex sound producing
      systems.

PMID- 20153889
TI  - Treating HIV infection with drugs for HSV-2 infection?

PMID- 20153890
TI  - The electron beam deposition of titanium on polyetheretherketone (PEEK) and the
      resulting enhanced biological properties.
AB  - The surface of polyetheretherketone (PEEK) was coated with a pure titanium (Ti)
      layer using an electron beam (e-beam) deposition method in order to enhance its
      biocompatibility and adhesion to bone tissue. The e-beam deposition method was a
      low-temperature coating process that formed a dense, uniform and well
      crystallized Ti layer without deteriorating the characteristics of the PEEK
      implant. The Ti coating layer strongly adhered to the substrate and remarkably
      enhanced its wettability. The Ti-coated samples were evaluated in terms of their
      in vitro cellular behaviors and in vivo osteointegration, and the results were
      compared to a pure PEEK substrate. The level of proliferation of the cells (MC3T3
      E1) was measured using a methoxyphenyl tetrazolium salt (MTS) assay and more than
      doubled after the Ti coating. The differentiation level of cells was measured
      using the alkaline phosphatase (ALP) assay and also doubled. Furthermore, the in
      vivo animal tests showed that the Ti-coated PEEK implants had a much higher bone
      in-contact (BIC) ratio than the pure PEEK implants. These in vitro and in vivo
      results suggested that the e-beam deposited Ti coating significantly improved the
      potential of PEEK for hard tissue applications.

PMID- 20153888
TI  - Daily acyclovir for HIV-1 disease progression in people dually infected with HIV
      1 and herpes simplex virus type 2: a randomised placebo-controlled trial.
AB  - BACKGROUND: Most people infected with HIV-1 are dually infected with herpes
      simplex virus type 2. Daily suppression of this herpes virus reduces plasma HIV-1
      concentrations, but whether it delays HIV-1 disease progression is unknown. We
      investigated the effect of acyclovir on HIV-1 progression. METHODS: In a trial
      with 14 sites in southern Africa and east Africa, 3381 heterosexual people who
      were dually infected with herpes simplex virus type 2 and HIV-1 were randomly
      assigned in a 1:1 ratio to acyclovir 400 mg orally twice daily or placebo, and
      were followed up for up to 24 months. Eligible participants had CD4 cell counts
      of 250 cells per mL or higher and were not taking antiretroviral therapy. We used
      block randomisation, and patients and investigators were masked to treatment
      allocation. Effect of acyclovir on HIV-1 disease progression was defined by a
      primary composite endpoint of first occurrence of CD4 cell counts of fewer than
      200 cells per microL, antiretroviral therapy initiation, or non-trauma related
      death. As an exploratory analysis, we assessed the endpoint of CD4 falling to
      <350 cells per microL. Analysis was by intention to treat. The trial is
      registered with ClinicalTrials.gov, number NCT00194519. FINDINGS: At enrollment,
      the median CD4 cell count was 462 cells per microL and median HIV-1 plasma RNA
      was 4.1 log(10) copies per microL. Acyclovir reduced risk of HIV-1 disease
      progression by 16%; 284 participants assigned acyclovir versus 324 assigned
      placebo reached the primary endpoint (hazard ratio [HR] 0.84, 95% CI 0.71-0.98,
      p=0.03). In those with CD4 counts >or=350 cells per microL, aciclovir delayed
      risk of CD4 cell counts falling to <350 cells per microL by 19% (0.81, 0.71-0.93,
      p=0.002) INTERPRETATION: The role of suppression of herpes simplex virus type 2
      in reduction of HIV-1 disease progression before initiation of antiretroviral
      therapy warrants consideration. FUNDING: Bill & Melinda Gates Foundation.

PMID- 20153891
TI  - Biodegradable polyamino acid-based polycations as safe and effective gene carrier
      minimizing cumulative toxicity.
AB  - Gene delivery using cationic polymers has attracted much attention due to their
      potential advantages, such as large DNA loading capacity, ease of large-scale
      production, and reduced immunogenicity. We recently reported that polyplexes from
      poly[N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide] (P[Asp(DET)]), having an
      efficient endosomal escape due to pH-selective membrane destabilization, showed
      high transfection efficiency with minimal toxicity. Pharmacogenomic analysis
      demonstrated that P[Asp(DET)] also provided long-term security after
      transfection. We hypothesized that the biodegradability of P[Asp(DET)] played a
      significant role in achieving effective transfection. Gel permeation
      chromatography (GPC) and electrospray ionization mass spectrometry (ESI-MS)
      measurements of P[Asp(DET)] revealed their ability to undergo rapid degradation.
      In contrast, a derivative polycation, N-substituted polyglutamide (P[Glu(DET)]),
      showed no degradability, indicating that the degradation of P[Asp(DET)] was
      induced by a specific self-catalytic reaction between the PAsp backbone and the
      side-chain amide nitrogen. Degradation products of P[Asp(DET)] caused no
      cytotoxicity, even at high concentrations in the culture medium. Repeated
      transfection by administering the polyplexes for every 24h showed that
      biodegradable P[Asp(DET)] provided a continuous increase in transgene expression,
      while non-degradable P[Glu(DET)] showed a decrease in transgene expression after
      48h, coupled with fluctuations in expression profiles of endogenous genes. In
      vivo intraperitoneal injection of P[Asp(DET)] induced minimal inflammatory
      cytokine induction to a level comparable to that of normal saline. These results
      indicate that the biodegradability of P[Asp(DET)] played a key role in achieving
      safe and sustained transgene expression, by minimizing cumulative toxicity caused
      by polycations remaining in cells or in the body.

PMID- 20153892
TI  - Factors influencing osteoblast maturation on microgrooved titanium substrata.
AB  - In this study, we demonstrate surfaces with various dimensions of microgrooves
      fabricated by photolithography and subsequent acid etching that enhance various
      characteristics of titanium. Microgrooves with truncated V-shape in cross-section
      from 15 to 90 microm widths enabled us to report their exclusive effects on
      altering the surface chemistry and on enhancing the surface hydrophilicity, serum
      protein adsorption and osteoblast maturation on titanium substrata in a
      microgroove dimension-dependent manner. Further, acid etching and measurement
      direction separately affected the surface hydrophilicity results. By multiple
      correlation and regression analyses, surface chemistry, surface hydrophilicity
      and serum protein adsorption were determined to be the significant influential
      factors on osteoblast maturation. Within the limitations of this study, we
      conclude that combined submicron- and microtopography with relevant micro
      dimension and structure enhance various characteristics of titanium, including
      surface hydrophilicity, which act as the essential factors influencing the
      osteoblast maturation on microgrooved titanium substrata.

PMID- 20153893
TI  - Antibiotic-releasing porous polymethylmethacrylate constructs for osseous space
      maintenance and infection control.
AB  - The use of a strategy involving space maintenance as the initial step of a two
      stage regenerative medicine approach toward reconstructing significant bony or
      composite tissue defects in the craniofacial area, preserves the void volume of
      bony defects and could promote soft tissue healing prior to the subsequent
      definitive repair. One of the complications with a biomaterial-based space
      maintenance approach is local infection, which requires early, effective
      eradication, ideally through local antibiotic delivery. The purpose of this study
      is to develop a dual function implant material for maintaining osseous space and
      releasing an antibiotic to eliminate local infection in bony defects. Colistin, a
      polymyxin antibiotic, was chosen specifically to address infections with
      Acinetobacter species, the most common pathogen associated with combat-related
      traumatic craniofacial injuries. Porous polymethylmethacrylate (PMMA) constructs
      incorporating poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated
      by mixing a clinically used bone cement formulation of PMMA powder and
      methylmethacrylate liquid with a carboxymethylcellulose (CMC) hydrogel (40 or 50
      wt%) to impart porosity and PLGA microspheres (10 or 15 wt%) loaded with colistin
      to control drug release. The PMMA/CMC/PLGA construct featured mild setting
      temperature, controllable surface/bulk porosity by incorporation of the CMC
      hydrogel, reasonably strong compressive properties, and continuous drug release
      over a period of 5 weeks with total drug release of 68.1-88.3%, depending on the
      weight percentage of CMC and PLGA incorporation. The concentration of released
      colistin was well above its reported minimum inhibitory concentration against
      susceptible species for 5 weeks. This study provides information on the
      composition parameters that enable viable porosity characteristics/drug release
      kinetics of the PMMA/CMC/PLGA construct for the initial space maintenance as part
      of a two-stage regenerative medicine approach.

PMID- 20153894
TI  - Extended delivery of hydrophilic drugs from silicone-hydrogel contact lenses
      containing vitamin E diffusion barriers.
AB  - This paper proposes an approach for increasing drug release durations from
      contact lenses and other biomedical devices by in situ creation of transport
      barriers of Vitamin E that force drug molecules to diffuse through long tortuous
      path. Results show that the increase in release duration is quadratic in Vitamin
      E loading, which is consistent with proposed mathematical models. Loadings of 10
      and 40% Vitamin E increase release time of timolol by a factor of about 5 and
      400, respectively for NIGHT&DAY lens. Similar results have been obtained for
      other hydrophilic drugs including fluconazole and dexamethasone 21-disodium
      phosphate (DXP). Vitamin E loading in the NIGHT&DAY lens leads to slight increase
      in lens sizes (6.5% increase for 30% loading), a slight reduction in oxygen
      diffusion (about 40% reduction for 75% loading), and a more significant reduction
      in the ion permeability (50% reduction for 10% loading). Additionally, Vitamin E
      loading has a beneficial effect of blocking UV radiation which will reduce the
      corneal damage due to UV light.

PMID- 20153895
TI  - Cell surface topology creates high Ca2+ signalling microdomains.
AB  - It has long been speculated that cellular microdomains are important for many
      cellular processes, especially those involving Ca2+ signalling. Measurements of
      cytosolic Ca2+ report maximum concentrations of less than few micromolar, yet
      several cytosolic enzymes require concentrations of more than 20 microM Ca2+ to
      be activated. In this paper, we have resolved this apparent paradox by showing
      that the surface topology of cells represents an important and hitherto
      unrecognized feature for generating microdomains of high Ca2+ in cells. We show
      that whereas the standard modeling assumption of a smooth cell surface predicts
      only moderate localized effects, the more realistic "wrinkled" surface topology
      predicts that Ca2+ concentrations up to 80 microM can persist within the folds of
      membranes for significant times. This intra-wrinkle location may account for 5%
      of the total cell volume. Using different geometries of wrinkles, our simulations
      show that high Ca2+ microdomains will be generated most effectively by long
      narrow membrane wrinkles of similar dimensions to those found experimentally.
      This is a new concept which has not previously been considered, but which has
      ramifications as the intra-wrinkle location is also a strategic location at which
      Ca2+ acts as a regulator of the cortical cytoskeleton and plasma membrane
      expansion.

PMID- 20153897
TI  - Thiopurine S-methyltransferase gene polymorphism and 6-mercaptopurine dose
      intensity in Indian children with acute lymphoblastic leukemia.
AB  - The prevalence of thiopurine S-methyltransferase (TPMT) polymorphism and its
      association with clinical and hematological toxicities was retrospectively
      analyzed in 71 Indian children with acute lymphoblastic leukemia (ALL). Only
      heterozygous TPMT alleles were observed (10%, 7/71) with relative frequencies
      being *1/*3C (4.2%), *1/*2 (4.2%) and *1/*3A (1.4%). The median 6-mercaptopurine
      dose administered during the maintenance therapy was 31% lower among patients
      with heterozygous TPMT alleles versus the rest (32.1mg/m(2)/day and
      46.2mg/m(2)/day, p=0.005), though the myelosuppression and toxicities were
      similar in both the groups. Identification of TPMT genotype appears to be
      important in making the ALL treatment more effective and less toxic.

PMID- 20153896
TI  - Contributions of SERCA pump and ryanodine-sensitive stores to presynaptic
      residual Ca2+.
AB  - The presynaptic Ca2+ signal, which triggers vesicle release, disperses to a
      broadly distributed residual [Ca2+] ([Ca2+](res)) that plays an important role in
      synaptic plasticity. We have previously reported a slowing in the decay
      timecourse of [Ca2+](res) during the second of paired pulses. In this study, we
      investigated the contributions of organelle and plasma membrane Ca2+ flux
      pathways to the reduction of effectiveness of [Ca2+](res) clearance during short
      term plasticity in Schaffer collateral terminals in the CA1 field of the
      hippocampus. We show that the slowed decay timecourse is mainly the result of a
      transport-dependent Ca2+ clearance process; that presynaptic caffeine-sensitive
      Ca2+ stores are not functionally loaded in the unstimulated terminal, but that
      these stores can effectively take up Ca2+ even during high frequency trains of
      stimuli; and that a rate limiting step of sarco-endoplasmic reticulum Ca2+-ATPase
      (SERCA) kinetics following the first pulse is responsible for a large portion of
      the observed slowing of [Ca2+](res) clearance during the second pulse. We were
      able to accurately fit our [Ca2+](res) data with a kinetic model based on these
      observations and this model predicted a reduction in availability of unbound
      SERCA during paired pulses, but no saturation of Ca2+ buffer in the endoplasmic
      reticulum.

PMID- 20153898
TI  - Molecular mechanisms involved in the inactivation of the first component of human
      complement by Trypanosoma cruzi calreticulin.
AB  - Trypanosoma cruzi (T. cruzi), the agent of Chagas' disease, the sixth most
      important neglected tropical disease worldwide, causes 50,000 deaths per year in
      Latin America. T. cruzi calreticulin (TcCRT), a highly pleiotropic chaperone
      molecule, plays important roles in several host/parasite interactions. Among
      other functions, we have previously shown that TcCRT, translocated from the
      endoplasmic reticulum to the area of flagellar emergence, binds human C1q and
      inhibits activation of the classical pathway in vitro. Based on a series of in
      vitro experiments, we propose here two mechanisms to explain how TcCRT inhibits
      the classical pathway at the initial stages of C1 (q, r, s) activation. First,
      TcCRT interacts in vitro with both solid phase bound active C1s and C1, but
      impairment of C4 activating capacity is evident only when the serine proteases
      are within the structural context of the macromolecular first component. Although
      C1s activity, in this context, is inhibited by TcCRT, the serine protease is not
      displaced from the C1 complex. Second, TcCRT prevents C1 formation, by
      interfering with the ability of the (C1r-C1s)(2) tetramer to bind C1q. These
      complement inhibitory effects are better explained by direct interaction of the
      parasite protein with C1, rather than by the TcCRT capacity to bind calcium, an
      essential element for the functional integrity of C1.

PMID- 20153899
TI  - A 10-year prospective audit of LASIK outcomes for myopia in 37,932 eyes at a
      single institution in Asia.
AB  - PURPOSE: This study evaluates the efficacy, predictability and safety of LASIK
      surgery as a treatment for myopia performed as part of a large-scale, prospective
      clinical audit spanning 10 years in an Asian study population and to evaluate the
      outcomes and trends. DESIGN: Prospective, nonrandomized, single-center,
      multisurgeon study. PARTICIPANTS: We included 37,932 eyes of 19,753 patients that
      underwent myopic LASIK at the Singapore National Eye Centre between 1998 and
      2007. METHODS: All eyes underwent LASIK as a treatment for myopia. Pre- and
      postoperative refractions, uncorrected visual acuity (UCVA), and best-corrected
      visual acuity (BCVA) were documented. MAIN OUTCOMES MEASURES: Safety, efficacy,
      refractive predictability, treatment trends, retreatment rates, and complications
      for mild, moderate, and high myopia according to spherical equivalence (SE) of
      less than -5.00 diopters (D), -5.00 D or more to less than -10.0 D, and -10.00 D
      or more, respectively. RESULTS: Patients' median age was 32 years (mean, 33.0+/
      7.9 years); there were 6832 males (34.6%) and 12,921 females included. Patients
      were predominantly ethnic Chinese (90.5%). Mean follow-up time was 68.8 days. The
      mean spherical error corrected was -5.90+/-2.57 D (median, -5.625 D), and
      outcomes were categorized into low, moderate, or high myopia. The UCVA achieving
      > or =20/40 has been consistently above 90% since 2000, with 72.8% achieving > or
      =20/20. More than 93.0% of eyes achieved within +/-1.00 D target in the last 4
      years. An improvement in safety was observed since the start of the study, with
      the best outcomes observed in 2007; loss of 1 and 2 Snellen line BCVA
      postoperatively was 2.4% and 0.1%, respectively. The overall retreatment rate was
      3.8%; 91% of retreated eyes achieved UCVA of > or =20/30. Between 1998 and 2007,
      there was a significant improvement in postoperative UCVA and BCVA (P<0.001).
      CONCLUSIONS: Myopic LASIK performed in Asian eyes within a comprehensive LASIK
      clinical program with appropriate clinical audit governance can be safe and
      effective, with high refractive predictability. Improvements in the nomograms to
      prevent undercorrection and to compensate for myopic regression have led to
      better efficacy after LASIK, with an increasing percentage of patients achieving
      20/15 visual acuity postoperatively.

PMID- 20153900
TI  - Vitamin E and age-related macular degeneration in a randomized trial of women.
AB  - OBJECTIVE: To test whether alternate day vitamin E affects the incidence of age
      related macular degeneration (AMD) in a large-scale randomized trial of 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 of natural-source vitamin E on alternate days
      or placebo. MAIN OUTCOME MEASURES: Incident AMD responsible for a reduction in
      best-corrected visual acuity to 20/30 or worse based on self-report confirmed by
      medical record review. RESULTS: After 10 years of treatment and follow-up, there
      were 117 cases of AMD in the vitamin E group and 128 cases in the placebo group
      (relative risk, 0.93; 95% confidence interval, 0.72-1.19). CONCLUSIONS: In a
      large-scale randomized trial of female health professionals, long-term alternate
      day use of 600 IU of natural-source vitamin E had no large beneficial or harmful
      effect on risk of AMD.

PMID- 20153901
TI  - The effect of amantadine on corneal endothelium in subjects with Parkinson's
      disease.
AB  - OBJECTIVE: To evaluate the effect of amantadine on corneal endothelial cells in
      subjects with Parkinson's disease. DESIGN: Cross-sectional study. PARTICIPANTS: A
      total of 169 subjects (169 eyes) taking amantadine orally for Parkinson's disease
      and the same number of age- and gender-matched controls. METHODS: Endothelial
      indices were compared between the amantadine-treated and age-matched control
      groups. The amantadine-treated group was divided into 3 subgroups according to
      the cumulative dose and duration of treatment. Endothelial changes were compared
      between the amantadine group and the normal control group, and among subgroups.
      MAIN OUTCOME MEASURES: Slit-lamp biomicroscopy, central corneal thickness (CCT),
      endothelial cell density (ECD), coefficient of variation, and hexagonality.
      RESULTS: The amantadine group had significantly lower ECD (mean +/- standard
      error; 2662.47+/-29.06 vs. 2784.72+/-25.89, P = 0.002), lower hexagonality
      (56.94+/-1.07 vs. 60.97+/-0.87, P = 0.004), and greater coefficient of variation
      (35.59+/-0.57 vs. 32.66+/-0.52, P = 0.000) compared with the age-matched control
      group. Longer duration and higher cumulative dose amantadine therapy led to a
      greater reduction in ECD (P<0.05) compared with the normal age-matched control
      group. CONCLUSIONS: Amantadine is more likely to have an effect on corneal
      endothelial cells in a dose-dependent manner when used long-term.

PMID- 20153902
TI  - Intentional and unintentional nonadherence to ocular hypotensive treatment in
      patients with glaucoma.
AB  - OBJECTIVE: To determine the rate of intentional and unintentional nonadherence in
      glaucoma patients and to identify associations between adherence behavior and
      patients' beliefs. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred
      thirty-one glaucoma patients using topical eye drops for at least 6 months.
      METHODS: Interviewer-administered surveys. MAIN OUTCOME MEASURES: Self-reported
      adherence and beliefs about glaucoma and its treatment were assessed using the
      Reported Adherence to Medication scale, the Brief Illness Perception
      Questionnaire, and the Beliefs about Medicines-Specific Questionnaire. RESULTS:
      Overall, 59 (45%) participants reported some degree of nonadherence, among whom
      39 (66.1%) reported unintentional nonadherence (e.g., forgetting), 10 (16.9%)
      reported intentional nonadherence (deliberate nonadherence), and 10 (16.9%)
      reported both forms of nonadherence. Compared with adherers, nonadherers were
      significantly younger, were less likely to have other nonocular health conditions
      or to use medicines other than their eye drops, and reported lower belief in the
      necessity of eye drops for glaucoma (P<0.05). Degree of unintentional
      nonadherence was associated with lower belief in necessity of eye drops, whereas
      degree of intentional nonadherence was associated with concerns about eye drops.
      CONCLUSIONS: Strategies aimed at improving adherence in glaucoma patients need to
      address both intentional and unintentional dimensions. Interventions focused on
      eliciting and addressing patients' beliefs and concerns about their eye drops
      require evaluation.

PMID- 20153903
TI  - Long-term treatment of multiple sclerosis with glatiramer acetate: natural
      history of the subtypes of anti-glatiramer acetate antibodies and their
      correlation with clinical efficacy.
AB  - A retrospective phase IV study was designed to evaluate the anti-GA antibody
      subtypes, test their in vitro neutralizing activity and correlate these
      parameters with the clinical efficacy, in long-term GA treatment of MS patients.
      Serum samples from 153 MS patients, 126 treated with GA for 2 to 15 years (mean
      6.6 years) and 27 treated for <2 years, were collected. Anti-myelin basic protein
      (MBP) and anti-GA antibodies were measured by specific ELISA. Neutralizing
      activity was determined by the capacity of the serum to inhibit the proliferation
      of GA-specific T-cells. Anti-GA antibodies were detected even after very long
      treatment periods, although at lower levels. Anti-MBP reactivity remained
      consistently negative. The IgG2 isotype of anti-GA antibodies and the multiple
      sclerosis severity scale (MSSS) was lower in the long-term treated patients
      P=0.0003 and 0.016 respectively. The neutralizing activity of anti-GA antibodies
      was insignificant. Our results indicate that the clinical efficacy of GA
      treatment could be associated with a decrease in anti-GA IgG2 isotype in long
      term GA-treated patients.

PMID- 20153904
TI  - Reliability analysis of time series force plate data of community dwelling older
      adults.
AB  - Frequency-based analysis of body sway has been used to distinguish between
      healthy young, healthy elderly adults and elderly adults with Huntingtons
      disease. Our aim was to assess the reliability of spectral-based outcomes of the
      centre of pressure (CoP) kinematics in order to determine if these outcomes could
      be tested for their capability to distinguish between elderly fallers and non
      fallers in a future study. We have studied balance for 30 community dwelling
      healthy older adults 60 years or older. Four test conditions were used. Three
      successive trials were performed for each condition. CoP kinematics were
      estimated with a force platform with three strain gauges set in a triangular
      position. The frequency content of these signals was estimated. Intrasession
      correlation coefficients (ICC's) were then calculated for all test conditions.
      The reliability of the selected parameters varied between low and high (ICC 0.652
      0.939). The ICC's for the narrow stance tests were higher compared to tests with
      normal standing conditions (0.771-0.94) to (0.652-0.865). The highest value was
      obtained in the high frequency band (0.939). These measures should be viewed with
      caution when screening geriatric patients because their reliability cannot always
      be assumed.

PMID- 20153905
TI  - Radiotherapy in early stage Hodgkin's lymphoma: The importance of volume and
      treatment position.
AB  - This planning study in Hodgkin's disease confirmed smaller irradiated volumes and
      subsequently lower doses to lungs, heart and breasts for involved node
      radiotherapy compared to involved field irradiation. However, shifting the arms
      from alongside the body to above the head offsets the observed benefit on dose to
      heart and breasts.

PMID- 20153906
TI  - Retrospective analysis of definitive radiotherapy for patients with superficial
      esophageal carcinoma: Consideration of the optimal treatment method with a focus
      on late morbidity.
AB  - PURPOSE: To evaluate the clinical efficacy of definitive radiotherapy for
      patients with superficial esophageal cancer. MATERIAL AND METHODS: From 1990
      through 2006, 97 patients with stage I disease were treated with radiotherapy
      with or without chemotherapy. All patients were diagnosed with panesophagoscopy
      and computed tomography. Chemotherapy was added in 61 patients, and intra
      cavitary brachytherapy (ICBT) was used in 27 patients. RESULTS: The patients were
      90 men and seven women with a median age of 65.7 years (range; 41-89). At last
      follow-up with a median follow-up duration of 35.7 months, 3 year-overall and
      progression-free survival (PFS) rates were 81.5% (95% C.I. = 73.3-89.7%) and
      55.8% (95% C.I. = 45.2-66.4%), respectively. Shorter tumor length was a
      significantly favorable factor for the PFS rate (P = 0.02) and local failure-free
      (LFF) rate (P = 0.007) on both univariate and multivariate analyses. Although the
      addition of ICBT had no apparent benefit for survival or tumor control, the rate
      of severe adverse effects including lethal esophageal ulcers, showed a higher
      tendency in patients receiving ICBT. CONCLUSIONS: Our results regarding efficacy
      from the viewpoint of organ preservation are promising. Special care would be
      taken for the use of ICBT for patients with superficial esophageal cancer,
      especially if they have received chemoradiotherapy.

PMID- 20153907
TI  - Prognostic significance of CD24 protein expression in patients treated with
      adjuvant radiotherapy after radical hysterectomy for cervical squamous cell
      carcinoma.
AB  - BACKGROUND AND PURPOSE: The CD24 marker is expressed in various carcinomas and is
      associated with shorter survival rates. We evaluated the prognostic significance
      of CD24 protein overexpression in patients treated with post-operative
      radiotherapy (RT) after surgery, and its prognostic significance and specific
      role stratified by adjuvant treatment modalities. MATERIALS AND METHODS: We
      determined the CD24 expression status of 140 patients with cervical squamous cell
      carcinoma treated with RT alone or with chemoradiotherapy (CRT) after radical
      hysterectomy procedures. RESULTS: CD24 expression was detected in 59 patients
      (42%) and was significantly associated with locoregional failure-free survival
      (LRFFS) (p=0.0218), distant metastasis-free survival (DMFS) (p=0.0001), and
      overall survival (OS) (p=0.0053). In the multivariate analysis, CD24 positivity
      was also significantly associated with DMFS (p=0.025) and OS (p=0.045). CD24
      expression stratified by post-operative treatments (CRT or RT alone) was
      associated with DMFS (p=0.0001) but not with LRFFS (p=0.4423) in the CRT group.
      However, CD24 expression was associated with LRFFS (p=0.0198) but not with DMFS
      (p=0.5269) in the RT alone group. CONCLUSIONS: CD24 expression is an independent
      prognostic marker in patients with cervical squamous cell carcinoma, even
      adjuvant treatment after surgery. And this study reveals different prognostic
      role of CD24 expression in two subgroups treated differently after surgery.
      Therefore, new therapeutic strategies targeting CD24 expression stratified by
      subgroups might have important clinical implications.

PMID- 20153908
TI  - The European Society of Therapeutic Radiology and Oncology-European Institute of
      Radiotherapy (ESTRO-EIR) report on 3D CT-based in-room image guidance systems: a
      practical and technical review and guide.
AB  - The past decade has provided many technological advances in radiotherapy. The
      European Institute of Radiotherapy (EIR) was established by the European Society
      of Therapeutic Radiology and Oncology (ESTRO) to provide current consensus
      statement with evidence-based and pragmatic guidelines on topics of practical
      relevance for radiation oncology. This report focuses primarily on 3D CT-based in
      room image guidance (3DCT-IGRT) systems. It will provide an overview and current
      standing of 3DCT-IGRT systems addressing the rationale, objectives, principles,
      applications, and process pathways, both clinical and technical for treatment
      delivery and quality assurance. These are reviewed for four categories of
      solutions; kV CT and kV CBCT (cone-beam CT) as well as MV CT and MV CBCT. It will
      also provide a framework and checklist to consider the capability and
      functionality of these systems as well as the resources needed for
      implementation. Two different but typical clinical cases (tonsillar and prostate
      cancer) using 3DCT-IGRT are illustrated with workflow processes via feedback
      questionnaires from several large clinical centres currently utilizing these
      systems. The feedback from these clinical centres demonstrates a wide variability
      based on local practices. This report whilst comprehensive is not exhaustive as
      this area of development remains a very active field for research and
      development. However, it should serve as a practical guide and framework for all
      professional groups within the field, focussed on clinicians, physicists and
      radiation therapy technologists interested in IGRT.

PMID- 20153909
TI  - Is pain the cause of altered biomechanical functions in back pain sufferers?
AB  - Alterations in movement patterns and muscle activities of the lumbar spine are
      frequently observed in patients with back pain. However there is considerable
      disagreement as to the underlying causative mechanisms. It is imperative to
      identify these mechanisms so that clinical management can be rationalized. One
      popular theory suggests these alterations are "pain-driven". This review presents
      a systematic appraisal, including effect size calculation of studies utilizing
      experimentally induced pain and experimental pain relief models to explore this
      concept. Fifteen studies were identified using MEDLINE and a review of reference
      lists. Experimentally induced pain did produce changes in electromyography and
      gait-related kinematics. However these effects were not universal. Experimental
      pain relief studies produced mixed results for improving maximal muscle function.
      These methodologies shared similar threats to validity and failed to fully answer
      the question due to methodological limitations; however possible mechanisms as to
      the effects of pain are discussed. Further research is required to resolve if
      pain is indeed the variable driving functional changes in kinematics and muscle
      functions observed in back pain sufferers, and if it is to what degree. Only then
      can management strategies begin to be rationalized.

PMID- 20153910
TI  - Competition and integration in Swedish health care.
AB  - Despite of an insignificant track record of quasi-market models in Sweden, new
      models of this kind have recently been introduced in health care; commonly
      referred to as "choice of care". This time citizens act as purchasers; choosing
      the primary care centre or family physician they want to be treated by, which, in
      turn, generates a capitation payment to the chosen unit. Policy makers believe
      that such systems will be self-remedial, that is, as a result of competition the
      strong providers survive while unprofitable ones will be eliminated. Because of
      negative consequences of the fragmented health care delivery, policy makers at
      the same time also promote different forms of integrated health care
      arrangements. One example is "local health care", which could be described as an
      upgraded community-oriented primary care, supported by adaptable hospital
      services, fitting the needs of a local population. This article reviews if it is
      possible to combine this kind of integrated care system with a competition driven
      model of governance, or if they are incompatible. The findings indicate that some
      choice of care schemes could hamper the development of integration in local
      health care. However, geographical monopolies like local health care, enclosed in
      a non-competitive context, lack the stimulus of competition that possibly
      improves performance. Thus, it could be argued that if choice of care and local
      health care should be combined, patients ought to choose between integrated
      health care arrangements and not among individual health professionals.

PMID- 20153911
TI  - Population-based patterns and cost of management of metastatic non-small cell
      lung cancer after completion of chemotherapy until death.
AB  - BACKGROUND: The aim of this study was to examine the patterns and costs of
      management of non-small cell lung cancer (NSCLC) after completion of chemotherapy
      until death in a population of patients in Manitoba, Canada. PATIENTS AND
      METHODS: Stage IIIB and IV NSCLC patients diagnosed between January 1997 and June
      2000 who received chemotherapy as the primary treatment, completed their
      chemotherapy and survived for at least 28 days since their last treatment, and
      were on best supportive care (BSC) were selected. Treatment, services received,
      costs, and survival were determined by chart review and examining various
      databases including the Manitoba Cancer Registry, medical claims,
      hospitalizations, and prescription drugs. Costs of treatment, average cost per
      patient, and lifetime treatment costs were calculated. RESULTS: Of the 2463
      patients diagnosed with NSCLC over the study period, 150 patients matched our
      study criteria. From the beginning of the first chemotherapy treatment, the
      median survival time was 31.8 weeks, while from the date of BSC the median
      survival time was 13.8 weeks. The average cost per case was $10,805 from last
      date of chemotherapy and $8654 during the BSC period. The average cost per
      patient-month ranged from $1645 to $1792 in current prices. Lifetime treatment
      costs ranged from $8702 to $11,057. Hospitalizations accounted for 80% of the
      total treatment costs. CONCLUSION: The largest overall component of cost after
      the end of chemotherapy was hospitalizations. Effective new therapies that reduce
      the episodes of hospitalizations would have a significant impact on decreasing
      aggregate costs.

PMID- 20153912
TI  - Phase I/II trial of gemcitabine plus oral TS-1 in elderly patients with advanced
      non-small cell lung cancer: Thoracic oncology research group study 0502.
AB  - A phase I/II trial of TS-1 combined with gemcitabine was designed to determine
      the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the
      efficacy and toxicity in elderly patients with advanced non-small cell lung
      cancer (NSCLC). Patients older than 70 years of age received TS-1 orally b.i.d.
      on days 1-14 and gemcitabine intravenously on days 8 and 15 every 4 weeks. In
      phase I (n=22), each cohort received escalating doses of TS-1 (30-40 mg/m(2)
      b.i.d.) and gemcitabine (800-1000 mg/m(2)); MTD was 40 mg/m(2) b.i.d. TS-1 and
      1000 mg/m(2) gemcitabine; RD was 30 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2)
      gemcitabine. Dose-limiting toxicities included a grade 3 infection, skin
      toxicity, and stomatitis. In phase II (n=37), the overall response rate was 27%
      (90% confidence interval (CI): 15-42%) and the median time to progression and
      overall survival were 4.2 months (90% CI: 3.2-5.7) and 12.9 months (90% CI: 10.4
      14.7), respectively. The most common grade 3 or higher toxicity was neutropenia
      (45.9%), and thrombocytopenia was observed in 13.5% of patients. Two cases each
      of grade 3 pneumonitis and skin toxicity were observed, but nonhematological
      toxicities occurred at generally low frequencies. TS-1 with gemcitabine is a
      promising doublet regimen in elderly patients with advanced NSCLC with acceptable
      toxicities.

PMID- 20153913
TI  - Is risk of pleural mesothelioma an environmental risk outside Turkey? A study on
      immigrants to Sweden.

PMID- 20153914
TI  - [Contribution of in vivo confocal microscopy to diagnosis of invasive ocular
      surface squamous neoplasia: a case report].
AB  - INTRODUCTION: Ocular surface squamous neoplasia (OSSN) is the most common
      conjunctival and limbic malignant tumor that could resemble a pterygium in the
      early phase of the disease. CASE REPORT: We report the case of a woman who
      presented with a limbic tumor of the left eye that was mistakenly diagnosed as a
      pterygium. An in vivo confocal microscopy examination using the HRTII Rostock
      Cornea Module and a surgical biopsy were performed. The in vivo confocal
      microscopy findings and the slit lamp examination showed characteristics that
      strongly supported the diagnosis of OSSN, and the histological examination of
      both biopsy and surgical exeresis (exenteration) confirmed the diagnosis of
      epidermoid carcinoma. CONCLUSION: This case report underlines the value of in
      vivo confocal microscopy in the diagnosis of OSSN, particularly epidermoid
      carcinoma. This device could be helpful for the early differential diagnosis with
      pterygium.

PMID- 20153915
TI  - Synthesis and biological activity of Delta-5,6-norcantharimides: importance of
      the 5,6-bridge.
AB  - Cantharidin (1) and norcantharidin (2) are potent protein phosphatase 1 and 2A
      inhibitors that also display high levels of anticancer activity against a broad
      range of tumor cells lines. Surprisingly, Delta-5,6-ethyl norcantharidin (3, cis
      tetrahydrofurano[3,4-c]furan-1,3-dione) displays neither phosphatase inhibition
      nor anticancer activity. This suggests that the 5,6-ethyl bridge is pivotal to
      both anti-cancer and protein phosphatase activity. Additionally bioisosteric
      replacement of the ethereal oxygen has no effect on biological activity nor does
      modification of the anhydride moiety. Unlike the parent norcantharidin, anhydride
      ring opening has no effect on either protein phosphatase inhibition or anti
      cancer activity. Additionally, this work highlights the discovery of the octyl
      substituted, cis-5-benzyl-2-hexyltetrahydro-2H,3aH-pyrrolo[3,4-c]pyrrole-1,3
      dione, 9p, and the octyl substituted, cis-octyltetrahydro-5H-furo[3,4-c]pyrrole
      4,6-dione, 8p, as two new cytotoxic agents which are equipotent (9p) with, and
      more potent (8p) than norcantharidin.

PMID- 20153916
TI  - Proximal humerus fracture rotational stability after fixation using a locking
      plate or a fixed-angle locked nail: the role of implant stiffness.
AB  - BACKGROUND: Fixed-angle locked devices have been developed to improve internal
      fixation of proximal humerus fractures. Available low-profile precontoured
      locking plates and intramedullary nails with fixed-angle interlocks are currently
      favored by most surgeons in this setting. The aim of this study was to assess the
      relative stability of these two methods of fixation under torsion load. METHODS:
      A surgical neck osteotomy was created in six pairs of embalmed humeri. In each
      pair, one specimen was secured with a titanium locking-compression plate, and the
      contralateral was secured with a titanium nail with a proximal locked spiral
      blade. The specimens were first tested cyclically in internal-external rotation
      for 10,000 cycles to evaluate interfragmentary motion (dynamic study). At the end
      of the cyclic testing, the specimens were loaded to failure in external rotation
      to measure torque to failure and construct stiffness (static study). FINDINGS:
      There were no significant differences in interfragmentary motion between the two
      fixation devices in the dynamic study. When tested to failure, fixation with the
      locking plate tolerated on average 20 more degrees in torsion before failure, and
      demonstrated higher torsional load to failure and less torsional stiffness
      (P<0.05). INTERPRETATION: Both locking plates and locked intramedullary nails may
      provide enough stability to avoid secondary displacement of proximal humerus
      fractures during early physical therapy. Locking plates demonstrated superior
      biomechanical properties under high rotational loads than locked intramedullary
      nails in a cadaveric proximal humerus two-part osteotomy model, and could provide
      more protection against unexpected high torsion loads.

PMID- 20153917
TI  - Prevalence and risk factors for CKD in spouses and relatives of hemodialysis
      patients.
AB  - BACKGROUND: A higher prevalence of chronic kidney disease (CKD) has been found in
      genetic relatives of patients with end-stage renal disease. However, the risk of
      CKD in nongenetic spouses of patients with end-stage renal disease is still
      unknown. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 196 first-
      and second-degree relatives and 95 spouses of 178 hemodialysis (HD) patients were
      enrolled. Two sex- and age-stratified matched counterpart controls were randomly
      selected from the population of a community screening program for CKD.
      PREDICTORS: Relatives or spouses of HD patients and kidney disease risk factors.
      OUTCOMES: Prevalence of CKD (albuminuria or low estimated glomerular filtration
      rate). MEASUREMENT: Albuminuria (urine albumin-creatinine ratio > or = 30 mg/g),
      low estimated glomerular filtration rate (<60 mL/min/1.73 m(2)), and kidney
      disease risk factors of age, hypertension, diabetes mellitus, metabolic syndrome,
      and lifestyle. RESULTS: A significantly higher prevalence of CKD was found in
      relatives (15.8% vs 7.5%; P = 0.01) and spouses (41.1% vs 15.8%; P < 0.001) of HD
      patients compared with their counterpart controls. Multiple logistic regression
      analysis showed that age (OR, 1.05) and hypertension (OR, 3.13) were significant
      independent risk factors for CKD in relatives of HD patients, whereas diabetes
      mellitus (OR, 3.51) was a significant risk factor for CKD in spouses of HD
      patients. For all pooled participants, being relatives (OR, 2.55) or spouses (OR,
      2.80) of HD patients, age (OR, 1.06), female sex (OR, 1.81), diabetes mellitus
      (OR, 3.95), hypertension (OR, 1.85), and hyperuricemia (OR, 2.06) were
      independent significant risk factors for CKD. LIMITATIONS: Cross-sectional
      research design, single laboratory measurement, and limited numbers of
      participants. CONCLUSIONS: A comprehensive screening program for CKD is equally
      important in both relatives and spouses of HD patients, especially for
      participants with the renal risk factors of older age, hypertension, and diabetes
      mellitus. Spousal concordance of CKD suggests that the shared environmental
      factors and health behaviors might have important roles in the development of
      CKD.

PMID- 20153918
TI  - CKD in a patient with pancreatic carcinoma.

PMID- 20153919
TI  - Sonographic lesions in fecal incontinence of obstetric origin Obstetric sphinter
      rupture.

PMID- 20153920
TI  - Reproductive fitness advantage of BCR-ABL expressing leukemia cells.
AB  - Mutations in oncogenes and tumor suppressor genes confer a fitness advantage to
      cells that can lead to cancer. The tumor phenotype normally results from the
      interaction of many mutant genes making it difficult to estimate the fitness
      advantage provided by any oncogene, except when tumors depend on one oncogene
      only. We utilize a model of chronic myeloid leukemia (CML), to quantitate the
      fitness advantage conferred by expression of BCR-ABL in hematopoietic cells from
      in vivo patient data. We show that BCR-ABL expression provides a high fitness
      advantage, which explains why this single mutation drives the chronic phase of
      CML.

PMID- 20153922
TI  - Fusicoccin-A selectively induces apoptosis in tumor cells after interferon-alpha
      priming.
AB  - Active small molecules have a high potential for the development into new anti
      cancer drugs. Here we analysed the effect of the natural occurring fusicoccanes,
      Fusicoccin-A (FC), Ophiobolin-A (OPH-A) and Ophiobolin-I (OPH-I) on various tumor
      cell lines. Both FC and OPH-A inhibit tumor cell growth efficiently, in contrast
      to OPH-I. Further analysis showed that FC is tumor specific, and that its
      efficacy can be enhanced by combining it with the cytokine interferon-alpha (IFN
      alpha). In this, IFN-alpha primes the tumor cells for apoptosis induction by FC,
      in which DR4 and the TRAIL pathway plays an important role. Healthy cells
      (HUVECs, Human Umbilical Vein Endothelial Cells) are far less sensitive to IFN
      alpha/FC treatment and need the continuous presence of both compounds in order to
      achieve a growth reduction. This differential response between healthy and tumor
      cells indicates that the IFN-alpha/FC treatment is a promising new cancer
      treatment, especially when IFN-alpha and FC are used sequentially.

PMID- 20153921
TI  - EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization
      of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity.
AB  - EGFR and its constitutively activated variant EGFRvIII are linked to glioblastoma
      resistance to therapy, the mechanisms underlying this association, however, are
      still unclear. We report that in glioblastoma, EGFR/EGFRvIII paradoxically co
      expresses with p53-upregulated modulator of apoptosis (PUMA), a proapoptotic
      member of the Bcl-2 family of proteins primarily located on the mitochondria.
      EGFR/EGFRvIII binds to PUMA constitutively and under apoptotic stress, and
      subsequently sequesters PUMA in the cytoplasm. The EGFR-PUMA interaction is
      independent of EGFR activation and is sustained under EGFR inhibition. A Bcl
      2/Bcl-xL inhibitor that mimics PUMA activity sensitizes EGFR/EGFRvIII-expressing
      glioblastoma cells to Iressa. Collectively, we uncovered a novel kinase
      independent function of EGFR/EGFRvIII that leads to tumor drug resistance.

PMID- 20153923
TI  - The ubiquitin-proteasome system is inhibited by p53 protein expression in human
      ovarian cancer cells.
AB  - The ubiquitin-proteasome system (UPS) and autophagy provide major cellular
      pathways for protein degradation. Since the p53 pathway controls autophagy, we
      investigated whether p53 regulates UPS in ovarian tumour cell lines. A reporter
      cell line (SKOV3-EGFPu) was established to measure UPS function against a
      constant genetic background. Transient expression of either wild type or mutant
      p53 in SKOV3-EGFPu cells reduced UPS activity as compared to vector control.
      These results, together with those from endogenous p53 expression in seven
      ovarian cancer cell lines, suggest that expression of both wild-type and mutant
      p53 protein impairs UPS function. Thus, p53 expression may regulate protein
      homeostasis by down-regulating UPS function in response to cellular stress.

PMID- 20153924
TI  - The BH3-mimetic GX15-070 induces autophagy, potentiates the cytotoxicity of
      carboplatin and 5-fluorouracil in esophageal carcinoma cells.
AB  - Despite improvements in both surgical techniques and radio- and chemo-therapy
      regimens, the prognosis of esophageal cancer is poor. In pursuit of novel
      effective strategy, this study examined the effect of the BH3-mimetic GX15-070 on
      esophageal carcinoma cells. We discovered that GX15-070 inhibited the growth of
      esophageal cancer cells. There was synergism between GX15-070 and carboplatin or
      5-fluorouracil. GX15-070 induced autophagy in esophagus cancer cell line EC9706
      and osteosarcoma cancer cell line U2OS. 3-methyladenine and chloroquine,
      inhibitors of autophagy with distinct mechanisms, potentiated the cytotoxicity of
      GX15-070. In conclusion, GX15-070 inhibits growth of esophageal cancer cells.

PMID- 20153925
TI  - MYCN oncoprotein targets and their therapeutic potential.
AB  - The MYCN oncogene encodes a transcription factor which is amplified in up to 40%
      of high risk neuroblastomas. MYCN amplification is a well-established poor
      prognostic marker in neuroblastoma, however the role of MYCN expression and the
      mechanisms by which it acts to promote an aggressive phenotype remain largely
      unknown. This review discusses the current evidence identifying the direct and
      indirect downstream transcriptional targets of MYCN from recent studies, with
      particular reference to how MYCN affects the cell cycle, DNA damage response,
      differentiation and apoptosis in neuroblastoma.

PMID- 20153926
TI  - Characterization of the microbial community from the marine sediment of the
      Venice lagoon capable of reductive dechlorination of coplanar polychlorinated
      biphenyls (PCBs).
AB  - The native microbial community of a contaminated sediment from Brentella Canal
      (Venice Lagoon, Italy) was enriched in slurry microcosms consisting of sterile
      sediment suspended in sterile site water in the presence of 3,3',4,4'
      tetrachlorobiphenyl, 3,3',4,4',5- and 2,3',4,4',5-pentachlorobiphenyls,
      3,3',4,4',5,5'- and 2,3,3',4,4',5-hexachlorobiphenyls. The enrichment cultures
      were characterized at each subculturing step by 16S rRNA gene Terminal
      Restriction Fragment Length Polymorphism (T-RFLP) and Denaturing Gradient Gel
      Electrophoresis (DGGE) analysis. About 90% of spiked polychlorinated biphenyls
      (PCBs) were stoichiometrically converted into di- and tri-chlorinated congeners
      by each enriched culture via dechlorination of flanked para chlorines and ortho
      flanked meta chlorines. A 2-fold increase in PCB-dechlorination rate, the
      disappearance of lag phase, as well as a remarkable increase of sulfate
      consumption and a decline of methanogenic activity, were observed throughout
      subculturing. A reduction of complexity of the archaeal community, which was
      composed by Methanomicrobiales and Methanosarcinales, was also observed as a
      result of culture enrichment. The bacterial community included members of the
      Alpha, Gamma, Delta and Epsilon divisions of Proteobacteria, Firmicutes and
      Chloroflexi. Two sequence phylotypes related to the genus Sulforovum and the
      species Desulfococcus multivorans and two Chloroflexi enriched throughout
      subculturing, thus suggesting that these bacteria were involved in PCB
      dechlorination in the marine sediments of Brentella canal.

PMID- 20153927
TI  - Scanning electron microscopic study of hazardous waste flakes of polyethylene
      terephthalate (PET) by aminolysis and ammonolysis.
AB  - Polyethylene terephthalate (PET) waste flakes were degraded with aqueous
      methylamine and aqueous ammonia, respectively at room temperature in the presence
      and absence of quaternary ammonium salt as a catalyst for different periods of
      time. The aminolysed and ammonolysed PET samples were investigated for the
      surface morphology with the help of scanning electron micrograph (SEM). It shows
      that the semi-crystalline PET waste samples reduce to monodisperse rods before
      fully degradation to the end products. The presence of the catalyst provides site
      for degradation of PET waste and enhances the rate of degradation. The SEM shows
      early developments of fissures in comparison to the one in absence of quaternary
      ammonium salt used as catalyst.

PMID- 20153928
TI  - Dye removal from aqueous solution by magnetic alginate beads crosslinked with
      epichlorohydrin.
AB  - Innovative magnetic alginate beads are used to remove organic pollutants from
      aqueous solution under different experimental conditions. These alginate beads
      (EpiMAB) are prepared by an extrusion technique and crosslinked with
      epichlorohydrin. They contain both magnetic nanoparticles and activated carbon
      (AC). With the addition of magnetic properties, the beads can be easily recovered
      or manipulated with an external magnetic field. Their capacity to adsorb
      pollutants is linked to encapsulated AC and to active sites coming from both
      magnetic nanoparticles and alginate. The efficiency of the beads as biosorbent
      for the removal of dyes is assessed using methyl orange (MO) and methylene blue
      (MB) as model molecules. The dye uptake is found to vary with the initial
      concentration and the charge of the adsorbed molecule. The Langmuir equation fits
      well the adsorption data with maximum adsorption capacities of 0.02 mmol/g for MO
      and 0.7 mmol/g for MB. Kinetics experiments are performed to evaluate the
      equilibrium time; the pseudo-second-order kinetic model adequately describes the
      experimental data. The influence of the pH of the solution on adsorption is also
      investigated and a comparison with alginate beads crosslinked by calcium ions is
      made.

PMID- 20153929
TI  - Sympathetic skin response following painful electrical stimulation is increased
      in major depression.
AB  - Patients with major depressive disorder have repeatedly been described to exhibit
      increased thresholds upon experimentally applied pain stimuli to the skin as
      compared to respective controls. Since the sensory-discriminative component of
      stimulus perception, e.g. for warmth, cold and vibration, appears to be unaltered
      in depression, higher central nervous centres have been assumed to cause this
      phenomenon. To date, hardly any attention has been paid to the efferent
      components of the noxious reflex loop. Here, we aimed to assess the autonomic
      reaction upon a painful stimulus and to examine whether this is likewise reduced
      in major depression. For this purpose, sympathetic skin response was obtained
      from 22 patients with major depression and 20 matched controls. To induce
      sympathetic skin responses, we applied either noxious electrical stimuli (12 and
      18 mA) or innocuous acoustic stimuli (85 dB SPL). Pain intensity was rated using
      a numeric analogue scale. In contrast to our a priori hypothesis patients showed
      shorter latencies and higher amplitudes of skin potentials upon noxious
      stimulation, i.e. a stronger sympathetic response. Intriguingly, the noxious
      stimuli were still perceived less painful in the patient group. Pain perception
      weakly correlated with disease severity. From these data, we conclude that
      despite the diminished pain perception, the autonomic reflex loop following
      noxious stimulation is not affected in patients with major depressive disorder,
      and that the increase in sympathetic outflow is not directly related to the
      perceived pain as in controls, but might rather be attributed to the autonomic
      dysfunction known for the disease.

PMID- 20153930
TI  - Alteration of GABAergic and glycinergic mechanisms by lidocaine injection in the
      rostral ventromedial medulla of neuropathic rats.
AB  - Attenuation of neuropathic manifestations in experimental animals, by lidocaine
      injection in the rostral ventro-medial medulla (RVM), has been traditionally
      attributed to selective block of a descending pain facilitatory system. However,
      the presence of descending fibers carrying this effect and the selective action
      of lidocaine on the facilitatory neurons, have not been supported by convincing
      experimental evidence. The present study aimed to investigate the mechanisms
      underlying the hypoalgesic action of lidocaine injection in the brainstem.
      Several groups of rats were subjected to mononeuropathy on their left hind paws,
      according to the model of spared nerve injury, and were subsequently implanted
      with guide cannulae in the RVM. After recovery, rats received injections of
      lidocaine, GABA and glycine agonists or antagonists and their effects were
      assessed on behavioral tests of allodynia and hyperalgesia. Injections of
      lidocaine at doses ranging between 0.05% and 2% produced attenuation at high
      doses and no effects or increasing hyperalgesia at low doses. GABA and glycine
      agonists increased neuropathic manifestations while their antagonists elicited
      the opposite effects. A combined injection of GABA agonist or glycine with
      lidocaine (0.5%) prevented the inhibitory effects of lidocaine injection alone.
      Our results are in line with the abundant documentation on the alteration of the
      function of inhibitory neurons by lidocaine and reveal a possible action of the
      injected high doses on the GABAergic and glycinergic neurons in the RVM. The
      resulting block of the inhibitory tone exerted by these neurons can lead to a
      release of the descending pain inhibitory systems.

PMID- 20153931
TI  - Performance of a Metarhizium anisopliae-treated semiochemical-baited trap in
      reducing Amblyomma variegatum populations in the field.
AB  - Experiments were carried out to evaluate the efficacy of Metarhizium anisopliae
      (Metsch.) Sorok. (Ascomycota: Hypocreales)-treated semiochemical-baited traps for
      control of Amblyomma variegatum Fabriscius (Acari: Ixodidae) under field
      conditions. Unfed A. variegatum adults (118) were seeded in each 100-m plot and
      allowed to acclimatise for 3 days. On the fourth day (Day 4), an emulsifiable
      formulation of M. anisopliae (consisting of 49.5% sterile distilled water, fungal
      conidia, 49.5% corn oil and 1% Tween 80) titrated at 10(9)conidia ml(-1) was
      applied in semiochemical-baited traps (900 cm(2)) which were placed at five spots
      within the plot. The control and fungal treatments were repeated after 14 and 28
      days soon after rotating the traps clockwise (45 degrees ) in order to cover
      different sections of the plot. In the control plots, emulsifiable formulation
      without fungus was applied in the semiochemical-baited traps. Six weeks after the
      initiation of the experiments, five semiochemical-baited traps (untreated) were
      deployed in each plot for 3 successive days to trap ticks in the treated and
      control plots. The percentage of ticks recovered in the fungus-treated plots were
      significantly lower (31.1+/-5.2%) than in the control plots (85.6+/-3%)
      (P<0.001), which represented a relative tick reduction of 63.7%. Mortality of
      93.8+/-2.3% was observed among the ticks that were recovered from the field and
      maintained in the laboratory for 2 weeks; while only 3.3+/-0.9% died from the
      control plots. The results of this study open up the possibility of developing an
      environmentally friendly and low cost application strategy to control Amblyomma
      ticks.

PMID- 20153932
TI  - The control of inhibited fourth-stage larvae of Haemonchus contortus and
      Teladorsagia spp. in sheep in Australia with monepantel.
AB  - Monepantel is the first molecule from the amino-acetonitrile derivatives to be
      developed for controlling gastro-intestinal nematodes in sheep. Two studies were
      undertaken to examine the drug's efficacy against inhibited fourth-stage larvae
      of Haemonchus contortus and Teladorsagia spp. in sheep when administered as an
      oral solution at 2.5mg/kg bodyweight. In study 1, efficacy was 99.7% against H.
      contortus (p<0.0001) and in study 2, 99.8% against Teladorsagia spp. (p<0.0001).
      This population consisted of 93% T. circumcincta and 7% T. trifurcata. In
      conclusion, monepantel is a highly effective treatment against inhibited fourth
      stage larvae of H. contortus and Teladorsagia spp. and the studies reported here
      provide the first published evidence of efficacy of this new anthelmintic against
      these parasites.

PMID- 20153933
TI  - The international trade in reptiles (Reptilia)--the cause of the transfer of
      exotic ticks (Acari: Ixodida) to Poland.
AB  - The problem of the unnatural transfer of exotic ticks (Acari: Ixodida) on
      reptiles (Reptilia) imported to Poland is presented. In the period from 2003 to
      2007, 382 specimens of reptiles belonging to the following genera were
      investigated: Testudo, Iguana, Varanus, Gongylophis, Python, Spalerosophis,
      Psammophis. The reptiles most infested with ticks are imported to Poland from
      Ghana in Africa, and are the commonly bred terrarium reptiles: Varanus
      exanthematicus and Python regius. As a result of the investigations, the transfer
      of exotic ticks on reptiles to Poland was confirmed. There were 2104 specimens of
      the genera Amblyomma and Hyalomma. The following species were found: Amblyomma
      exornatum Koch, 1844, Amblyomma flavomaculatum (Lucas, 1846), Amblyomma latum
      Koch, 1844, Amblyomma nuttalli Donitz, 1909, Amblyomma quadricavum (Schulze,
      1941), Amblyomma transversale (Lucas, 1844), Amblyomma varanense (Supino, 1897),
      Amblyomma sp. Koch, 1844, Hyalomma aegyptium (Linnaeus, 1758). All the species of
      ticks of genus Amblyomma revealed have been discovered in Poland for the first
      time. During the research, 13 cases of anomalies of morphological structure were
      confirmed in the ticks A. flavomaculatum, A. latum and H. aegyptium. The
      expanding phenomenon of the import of exotic reptiles in Poland and Central
      Europe is important for parasitological and epidemiological considerations, and
      therefore requires monitoring and wide-ranging prophylactic activities to prevent
      the inflow of exotic parasites to Poland.

PMID- 20153934
TI  - Herpes and acoustic neuromas: is there a cause and effect to observe?
AB  - Acoustic neuromas are a result of damage to the affected nerve function and can
      potentially press surrounding tissues. Although some sources suggest that
      observation is the treatment of choice for only those over 65 years of age and
      those unable to tolerate undergoing surgery or radiosurgery, most affected
      individuals should strongly consider not doing any aggressive therapies. Herpes
      has already been shown to mimic acoustic neuroma clinically, but growing evidence
      suggests that it is likely the cause of most cases of this entity.

PMID- 20153936
TI  - Identification and characterization of spiralin-like protein SLP25 from
      Spiroplasma eriocheiris.
AB  - Spiroplasma eriocheiris causes tremor disease (TD) of Chinese mitten crab
      Eriocheir sinensis, but little is known about the molecular characterization of
      this pathogen. The present study was undertaken to identify a unique gene of
      spiroplasma, spiralin-like protein (SLP25) and analyze its character. The full
      length DNA of SLP25 is 699 bp encodes a protein of 232 amino acid residues. The
      theoretical isoelectric point and molecular weight for the SLP25 are 4.50 and
      24.67 kDa, respectively. The similarity of SLP25 deduced amino acid sequence,
      shared with the spiralin from other species, indicated that the gene might be a
      member of the spiralin family. After cloning the SLP25, the gene was site-mutated
      from TGA to TGG and transcribed in E. coli to full expression of the recombinant
      SLP25. Anti-SLP25 serum was prepared by immunization of rabbits. The titer of
      anti-SLP25 serum was about 1:20000. A SLP25 band was detected by anti-SLP25
      antibody using the total proteins of S. eriocheiris. A specific immunoreactive
      band was detected when anti-S. eriocheiris serum was opposed to the recombinant
      protein. This finding suggests that SLP25 could be a good antigen for
      immunodiagnosis of TD of E. sinensis.

PMID- 20153935
TI  - A pharmacogenetic model of naltrexone-induced attenuation of alcohol consumption
      in rhesus monkeys.
AB  - BACKGROUND: Variation at the human mu-opioid receptor has been associated with
      alcohol abuse. The A118G (N40D) polymorphism in humans is functionally mimicked
      by the C77G (P26R) polymorphism in rhesus monkeys; both show similar in vitro
      influences on ligand binding and in vivo correlations with physiological measures
      as well as behavioral measures including predilection towards alcohol
      consumption. Naltrexone, an antagonist at the receptor, has been used to treat
      alcoholism in humans and has been reported to show differences in effectiveness
      depending on genotype. METHODS: Here we describe a study in which we a priori
      selected rhesus monkeys based on genotype at the OPRM1 C77G single nucleotide
      polymorphism, trained them to self-administer alcohol, and assessed naltrexone
      responsiveness. RESULTS: Alcohol intake in rhesus monkeys varied with genotype
      across a range of alcohol concentrations (0.5-4%, w/v) such that animals with the
      G/G genotype drank consistently more alcohol than those animals with the C/C
      genotype. Additionally, naltrexone attenuated alcohol drinking in a dose- and
      genotype-dependent manner. Animals harboring the G/G genotype were more sensitive
      to the effects of naltrexone and showed greater reductions in alcohol consumption
      at lower naltrexone doses compared to animals with a C/G or C/C genotype.
      CONCLUSIONS: This preliminary study demonstrates a pharmacogenomic response to
      naltrexone in rhesus monkeys that parallels that seen in humans. This finding
      provides a basis for developing a pharmacogenetic animal model for naltrexone
      effect that can expand further our understanding of the causes and treatments of
      alcohol use disorders.

PMID- 20153937
TI  - Virological and pathological findings in Bluetongue virus serotype 8 infected
      sheep.
AB  - Twenty-seven sheep of the four most common Swiss breeds and the English breed
      Poll Dorset were experimentally infected with a northern European field strain of
      bluetongue virus serotype 8 (BTV-8). Animals of all breeds developed clinical
      signs, viremia and pathological lesions, demonstrating that BTV-8 is fully
      capable of replicating and inducing bluetongue disease (BT) in the investigated
      sheep. Necropsy performed between 10 and 16 days post-infectionem (d.p.i.)
      revealed BT-typical hemorrhages, effusions, edema, erosions and activation of
      lymphatic tissues. Hemorrhages on the base of the Arteria pulmonalis and the left
      Musculus papillaris subauricularis were frequently present. Histology confirmed
      the macroscopical findings. Using a score system, clinical manifestation and
      pathology were found to be significantly related. Furthermore, clinical signs and
      fever were shown to be indicative for the concurrent presence of high amounts of
      viral ribonucleic acid (RNA) in blood. Spleen, lung, lymph nodes and tonsils from
      all animals were analyzed regarding viral RNA loads and infectivity using real
      time reverse transcriptase PCR (rRT-PCR) and virus isolation in cell culture,
      respectively. The highest amount of viral RNA was detected in spleen and lung and
      rRT-PCR revealed to be a more sensitive method for virus detection compared to
      virus isolation. A long-term follow-up was performed with three sheep showing
      that BTV-8 viral RNA in blood was present up to 133 d.p.i. and in certain tissues
      even on 151 d.p.i. No significant breed-related differences were observed
      concerning clinicopathological picture and viremia, and the Swiss sheep were as
      susceptible to BTV-8 infection as Poll Dorset sheep, demonstrating a remarkably
      high virulence of BTV-8 for indigenous sheep breeds.

PMID- 20153938
TI  - Use of citrate adonitol agar as a selective medium for the isolation of
      Escherichia fergusonii from a captive reindeer herd.
AB  - Escherichia fergusonii is an emerging potentially zoonotic organism which has
      been recovered from a broad range of human and animal sources. Efforts to recover
      E. fergusonii from mixed flora hitherto however have been constrained by the lack
      of a suitable selective medium for its isolation. This paper reports for the
      first time the recovery of E. fergusonii from reindeer carcases in a wildlife
      park and the use of citrate adonitol agar to selectively screen for the presence
      of this organism in faecal samples from further animals in the park, and reindeer
      in their natural habitat in Norway.

PMID- 20153939
TI  - Evaluation of humoral and antigen-specific T-cell responses after vaccination of
      pigs against pseudorabies in the presence of maternal antibodies.
AB  - In this study the influence of maternal immunity against pseudorabies virus (PRV)
      on the development of humoral and T-cell mediated immune (CMI) responses was
      investigated under the experimental condition. Pigs born to immune sows were
      vaccinated with gE-deleted vaccine according to five different schedules.
      Peripheral blood mononuclear cells (PBMC), collected after vaccination, were used
      for PRV-induced lymphocyte proliferation assay (LPA). Antibodies to the gB and gE
      of PRV in serum were determined using ELISA kits. Maternally derived antibodies
      (MDA) in the serum of unvaccinated piglets born to immune sows were above the
      level considered to be positive until about 10-11 weeks of life. The active
      humoral as well as CMI responses was the highest in group vaccinated at 10 and 14
      weeks of age. The results of this study suggest that MDA may disturb or even
      block development of active humoral response. Early priming of T-cells with
      attenuated gE-deleted PRV vaccine in the presence of MDA could be successful, but
      obtaining a long-term cellular immunity at least one booster is required.

PMID- 20153940
TI  - Isolation and genetic characterization of H3N8 equine influenza virus from
      donkeys in China.
AB  - During the 2007 outbreak of equine influenza (EIV) in China, an influenza virus
      designated A/donkey/Xinjiang/5/2007 (donkey/Xinjiang/2007) was isolated from a
      symptomatic donkey in Xinjiang Uygur Autonomous Region, China. To analyze the
      genetic evolution of the new isolate, the hemagglutinin (HA) gene of
      donkey/Xinjiang/2007 was amplified and sequenced. Sequence alignment, prediction
      of glycosylation sites and phylogenetic analysis of the HA1 protein of
      donkey/Xinjiang/2007 showed most similarity to the Florida sublineage clade 2 of
      the American lineage of equine influenza viruses. The HA1 sequence of
      donkey/Xinjiang/2007 had high identity with the Chinese EIV strains isolated in
      recent years and had low identity with A/swine/Anhui/1/2006, a horse-derived
      influenza virus isolated from pigs in China. Compared with vaccine strains, the
      HA1 amino acid sequence of donkey/Xinjiang/2007 varied in the five putative
      antigenic sites to different degrees and distributed in a different branch of the
      HA1 phylogenetic tree. Our findings provide further evidence of an American H3N8
      equine influenza virus in China in addition to the European H3N8 equine influenza
      virus. Accordingly, a vaccine against equine influenza in China should contain
      components of both strains of viruses to prevent widespread infection.

PMID- 20153941
TI  - General movements in the perinatal period and its relation to echogenicity
      changes in the brain.
AB  - BACKGROUND: In preterm born infants abnormal general movements (GMs) generally
      normalize before three months post term, but may persist when perinatal brain
      injury is present. AIMS: To assess the continuity of GM quality from fetal to
      early neonatal period and its relation to brain echogenicity changes. STUDY
      DESIGN: Prospective study examining GMs and three vulnerable brain areas before
      and 7days after birth. The quality of GMs was classified as normal or abnormal by
      Gestalt-perception. The brain was examined for moderate echogenicity changes
      (periventricular: brighter than choroid plexus, intraventricular: filling equal
      or more than 50% of the ventricle, and locally increased basal ganglia/thalami).
      SUBJECTS: 94 fetuses from pregnancies complicated by preterm hypertensive
      disorders or labour at a gestational age between 26 and 34weeks. OUTCOMES
      MEASURES: Correlations of fetal GMs, echogenicity changes, and clinical
      parameters (e.g. gestational age, parity, hypertensive disorders or preterm
      labour, oligohydramnios and fetal growth restriction) with neonatal GMs. RESULTS:
      Fetal GMs were abnormal in 64%, normalizing in 68% within 7days after birth.
      Fetal GMs were significantly related to postnatal GMs (p=0.045). Moderate fetal
      brain echogenicity changes and clinical parameters were not significantly related
      to neonatal GM. CONCLUSIONS: In this population of pregnancies compromised by
      hypertensive disorders or preterm labour fetal GMs correlated with neonatal GMs.
      Presence of moderate echogenicity changes in the fetal brain was not related to
      neonatal GMs.

PMID- 20153942
TI  - Visual performance and brain structures in the developing brain of pre-term
      infants.
AB  - The presence of abnormal visual function has been related to overt lesions in the
      thalami, peritrigonal white matter (such as cavitational-necrotic periventricular
      leucomalacia) and optic radiations, and also to the extent of occipital cortex
      involvement. The normal development of visual function seems to depend on the
      integrity of a network that includes not only optic radiations and the primary
      visual cortex but also other cortical and subcortical areas, such as the frontal
      or temporal lobes or basal ganglia, which have been found to play a topical role
      in the development of vision. Therefore, the complex functions and functional
      connectivity of the developing brain of premature infants can be studied only
      with highly sophisticated techniques such as diffusion tensor tractography. The
      combined use of visual tests and neonatal structural and functional neuroimaging,
      which have become available for newborn infants, provides a better understanding
      of the correlation between structure and function from early life. This appears
      to be particularly relevant considering the essential role of early visual
      function in cognitive development. The identification of early visual impairment
      is also important, as it allows for early enrolment in intervention programmes.
      The association of clinical and functional studies to newer imaging techniques,
      which are being increasingly used also in neonates, are likely to provide further
      information on early aspects of vision and the mechanisms underlying brain
      plasticity, which are still not fully understood. Early exposure to a difficult
      postnatal environment together with early and unexpected removal from a
      protective milieu are exclusive and peculiar factors of prematurity that
      interfere with the normal development of the visual system in pre-term babies.
      The problem is further compounded by the influence of different perinatal brain
      lesions affecting the developing brain of premature babies. Nevertheless, in the
      last few decades, there have been considerable advances in our understanding of
      the development of vision in pre-term infants during early infancy. This has
      mainly been due to the development of age-specific tests assessing various
      aspects of visual function, from ophthalmological examination to more cortical
      aspects of vision, such as the ability to process orientation or different
      aspects of visual attention [1-7]. Improvements in understanding very early and
      specific neurological impairments in neurological functions have been reported in
      pre-term infants, known to be at risk of developing visual and visual-perceptual
      impairment. These impairments are due not only to retinopathy, a common finding
      in premature infants, but also to cerebral (central) visual impairment, secondary
      to brain lesions affecting the central visual pathway.

PMID- 20153943
TI  - Freezing canine sperm: comparison of semen extenders containing Equex and LDL
      (Low Density Lipoproteins).
AB  - Chicken egg yolk is held as an excellent cryoprotective agent for freezing canine
      semen. Recent advances have enabled the extraction of low density lipoproteins
      from egg yolk, which are responsible for the cryoprotective abilities of the
      latter. The objective of this article was to compare 3 semen extenders for
      freezing canine semen: 2 containing egg yolk (Tris egg yolk and Equex STAMP) and
      one containing 6% LDL. After freezing and thawing 20 ejaculates from 5 different
      dogs, the 6% LDL extender produced 50% mobile spermatozoa, compared with 48% with
      the Equex extender and 27.7% with the extender containing egg yolk alone (EY). In
      vitro functional tests demonstrated that the integrity of the plasma membrane
      (hypoosmotic test) was respected in 65-66% of spermatozoa as a function of the
      extender; DNA integrity was respected in more than 97% of the spermatozoa. The
      Equex extender provided superior acrosome integrity (FITC/PSA test): 68.4%
      compared with 55.1% with LDL and 53.3% with egg yolk. However, the 6% LDL
      extender resulted in fewer spermatozoal anomalies (Spermac test), with 54.6%
      normal spermatozoa compared to 53.6% for Equex and 53.3% with the egg yolk. All
      six of the bitches inseminated artificially via the intra-uterine route
      (Scandinavian technique) using semen frozen in the 6% LDL extender became
      pregnant. The LDL extender resulted in percentages of mobile spermatozoa and
      movement characteristics that were as good if not better than those obtained with
      the reference extenders following thawing. The 6% LDL extender appears to have
      the same cryoprotective qualities as the reference diluent, Equex STAMP.

PMID- 20153944
TI  - Increased reproductive success in the white American mink (Neovison vison) with
      chronic dietary beta-sitosterol supplement.
AB  - Beta-sitosterol is a weakly estrogenic phytosterol used in functional foods to
      lower elevated serum cholesterol concentrations. It has been reported to cause
      reproductive disturbances in fish and lower the sperm count of rodents but, in
      contrast, there were indications of enhanced reproduction in a preliminary study
      on the brown American mink (Neovison vison). In the present experiment the
      effects of chronic dietary beta-sitosterol exposure on the reproduction of the
      American mink were evaluated with a large number of experimental animals. Male
      and female finnwhite mink (n=200)--a previously uninvestigated color type with
      lower reproductive success compared to brown mink--were exposed to 50 mg beta
      sitosterol kg(-1)d(-1) for 10 months and compared with 200 control animals. After
      3 months in November, 15 males per group were sacrificed and their biochemical
      variables determined. The serum glucose and high-density lipoprotein cholesterol
      concentrations were lower in the beta-sitosterol-exposed group, while other
      effects were minor. The females were mated with the top-rated males (4-5:1) in
      March and their reproductive performance was determined. The reproductive success
      increased in the beta-sitosterol group with significantly fewer barren females
      and a higher number of successfully reproducing females than in the control
      group, which supports previous studies on brown mink and voles indicating that
      beta-sitosterol could be used to enhance the reproductive performance of these
      mammals.

PMID- 20153945
TI  - Occupational activity is associated with knee cartilage morphology in females.
AB  - INTRODUCTION: Knee osteoarthritis (OA) is a major cause of pain and disability in
      women, becoming a major health problem in mid to later life. A better
      understanding of factors contributing to deleterious structural knee changes may
      be important for preventing OA. In men, occupations associated with frequent knee
      bending have been shown to be associated with damage to knee cartilage. This has
      not been examined in women. The aim of this study was to examine the effect of
      occupational specific knee activities on tibial and patella cartilage morphology
      among healthy females. METHODS: 96 females aged 26-62 years with no history of
      knee injury or symptoms were recruited as part of a study of community-based
      study of lifestyle factors on knee health. Occupational activity data examining
      the frequency of tasks such as heavy lifting, knee bending, stair climbing,
      walking and standing were obtained by questionnaire. Tibial and patella cartilage
      volumes and defects were measured from magnetic resonance imaging using validated
      methods. RESULTS: Heavy lifting/bending/squatting, knee bending, stair climbing
      and walking were all associated with an increased risk of patella, but not
      tibial, cartilage defects (odds ratio 1.8-2.9; p<or=0.05) after adjustment for
      potential confounders, including knee alignment and radiographic joint space
      narrowing. There was a trend towards knee bending being associated with a
      reduction in patella cartilage volume (p=0.07). CONCLUSION: Our results
      demonstrate that asymptomatic adult females with occupations requiring frequent
      knee bending have patella, but not tibial cartilage damage. These findings
      suggest that vocational tasks requiring knee bending are detrimental to the
      structure of cartilage in females and may be an area to consider in the
      prevention of knee OA.

PMID- 20153946
TI  - Testosterone and the aging male: to treat or not to treat?
AB  - It is well-established that total testosterone (TT) in men decreases with age and
      that bioavailable testosterone (bio-T) falls to an even greater extent. The
      clinical relevance of declining androgens in the aging male and use of
      testosterone replacement therapy (TRT) in this situation is controversial. Most
      studies have been short term and there are no large randomized placebo-controlled
      trials. Testosterone has many physiological actions in: muscles, bones,
      hematopoietic system, brain, reproductive and sexual organs, adipose tissue.
      Within these areas it stimulates: muscle growth and maintenance, bone development
      while inhibiting bone resorption, the production of red blood cells to increase
      hemoglobin, libido, enhanced mood and cognition, erectile function and lipolysis.
      Anabolic deficits in aging men can induce: frailty, sarcopenia, poor muscle
      quality, muscle weakness, hypertrophy of adipose tissue and impaired
      neurotransmission. The aging male with reduced testosterone availability may
      present with a wide variety of symptoms which in addition to frailty and weakness
      include: fatigue, decreased energy, decreased motivation, cognitive impairment,
      decreased self-confidence, depression, irritability, osteoporotic pain and the
      lethargy of anemia. In addition, testosterone deficiency is also associated with
      type-2 diabetes, the metabolic syndrome, coronary artery disease, stroke and
      transient ischemic attacks, and cardiovascular disease in general. Furthermore,
      there are early studies to suggest that TRT in men with low testosterone levels
      may improve metabolic status by: lowering blood sugar and HbA1C in men with type
      2 diabetes, reducing abdominal girth, ameliorating features of the metabolic
      syndrome, all of which may be protective of the cardiovascular system. The major
      safety issue is prostate cancer but there is no evidence that supports the idea
      that testosterone causes the development of a de novo cancer. So on balance in a
      man with symptoms of hygonadism and low or lowish levels of testosterone with no
      evidence of prostate cancer such as a normal PSA a therapeutic (4-6 months) trial
      of TRT is justified. Treatment and monitoring of this duration will determine
      whether the patient is responsive.

PMID- 20153947
TI  - [Allergic risk during paediatric anaesthesia].
AB  - OBJECTIVES: To propose the different modalities of management of the allergic
      risk occurring during paediatric anaesthesia. STUDY DESIGN: Literature analysis.
      METHODS: Literature research using the Medline((R)) database and MeSH format
      according to keywords, including publications in French and English since 1982.
      RESULTS: The overall incidence for anaphylactic reactions was estimated at one in
      7741 anaesthetic procedures during paediatric anaesthesia. Latex anaphylaxis was
      mostly involved with an incidence at one in 10,159 anesthetic procedures. The
      risk factors of latex sensitization are known. Primary latex prophylaxis is
      efficient in patients at risk of latex sensitization. In contrast to adults,
      neuromuscular blocking agents (NMBAs) are rarely involved in children, with an
      incidence at 1 in 81,275 anaesthetic procedures. The Ring and Messmer clinical
      scale allows quantifying the severity and helps managing the care of immediate
      hypersensitivity reactions. Clinical symptoms associate cardiovascular,
      respiratory and cutaneous-mucous signs according to different severity grades.
      Epinephrine associated to fluid loading, remains the first-line agent in case of
      severe reactions. The allergological assessment is key to the management of these
      reactions and is required in order to identify the mechanism of the reaction and
      the culprit drug or substance involved. CONCLUSIONS: Allergic reactions to NMBAs
      occurring during paediatric anaesthesia are rare whereas those with latex are
      more frequent. Therefore, the reduction of the allergic risk during paediatric
      anaesthesia essentially requires a latex-free environment.

PMID- 20153948
TI  - Food refusal in children: a review of the literature.
AB  - Food refusal is a severe feeding problem in which children refuse to eat all or
      most foods presented and exhibit problems with growth. This review discusses the
      definition, etiology, and interventions pertaining to food refusal. The
      interventions utilized for food refusal typically consist of several treatment
      components. These treatment components are reviewed and implications for future
      interventions are discussed.

PMID- 20153949
TI  - Movement disorders in a twins pair: a casual expression or genetic determination?
AB  - A twin study is an excellent means of assessing the contribution of heritability
      to motor behaviour. We present a movement video-analysis of a monozygotic twins
      pair with a motor repertoire which is almost totally constituted by persistent
      and subcontinuous motor stereotypies. PURPOSE: The specific aim of this study is
      to verify the heritable quantum of motor behaviour and to determine which among
      the motor patterns we analysed are more likely to be conditioned by inheritance.
      METHODS: Stereotyped movements were videotaped in two standardized sessions: at
      rest and in relation to preordained sensory stimulations. We estimated the
      concordance index (CI) between the observers to evaluate the reliability of the
      observations. The validity was accepted as being CI>0.80. RESULTS: The results
      showed a very high concordance rate (>90%) for all the stereotypies analysed. An
      almost superimposable trend of the stereotyped movements was found both at rest
      and in relation to the sensory stimulations. CONCLUSIONS: Such strong data
      suggest that genetic factors have a primary influence on all the movement
      disorders analysed. This study contributes to a better understanding of the
      complex relationships between genes and functions.

PMID- 20153950
TI  - Screening for medical disease--nervous system disorders.
AB  - NARRATIVE REVIEW: In general, nervous system disorders present with changes in
      sensation, strength, and cognitive function that must be recognized early for the
      timely referral often needed for optimal outcome. This article summarizes
      screening for nervous system disorders in patients who present to the hand
      therapist and the typical findings associated with common neurologic disorders.
      Recommendations for referral by the hand therapist of patients with a screening
      examination consistent with a nervous system disorder are also presented. Central
      nervous system (CNS) disorders discussed in this article include stroke,
      traumatic brain and spinal cord injury, CNS tumors, Parkinson disease, dementia,
      epilepsy, and multiple sclerosis. This is followed by a discussion of the
      peripheral nervous system (PNS) disorders of acquired and hereditary
      polyneuropathies, Guillain-Barre syndrome and myasthenia gravis. Lastly, there is
      a brief discussion of amyotrophic lateral sclerosis, a disorder affecting both
      the CNS and PNS. LEVEL OF EVIDENCE: 5.

PMID- 20153951
TI  - Seizure severity and duration in the cortical stimulation model of experimental
      epilepsy in rats: a longitudinal study.
AB  - The aim of this study was to determine the current intensities necessary to
      elicit three levels of varying EEG and behavioural phenomena with electrical
      stimulation, and also to determine the consistency of the EEG and behavioural
      components of the triggered seizures over time. Electrical stimulation of the
      primary motor/somatosensory cortex was performed in 16 adult rats with
      multichannel microwire electrode arrays. Stimulation was delivered at a frequency
      of 60 Hz (1 ms pulse width), for 2 s duration, as biphasic rectangular pulses
      over four of the eight available electrode pairs. Current intensity thresholds
      for interruption of normal behaviour, epileptiform afterdischarge (EAD) longer
      than 5 s and motor seizures with Racine severity greater than 3 were not
      correlated to time post-surgery. The Racine threshold was shown to be negatively
      correlated to the EAD duration and Racine severity of seizures elicited in the
      following sessions. Seizures were reliably generated in rats through cortical
      stimulation with microwire electrode arrays and these seizures were not shown to
      be subject to any kindling type effects up to 53 days post-implantation. Both the
      electrographic duration and behavioural severity of stimulated seizures remained,
      on average, constant during this experimental period. Approximately one-third of
      stimulations did not cause observable motor seizures and of those that did result
      in seizures, forelimb clonus was the most common manifestation and the mean EAD
      duration was 18.5 s. No damage beyond that caused by surgical implantation of
      electrodes was observed in the histological analyses of stimulated and non
      stimulated tissue. The consistency, duration and severity of seizures within this
      timeframe make this cortical stimulation model suitable for investigations into
      novel therapeutic interventions for epilepsy that require a known seizure focus.

PMID- 20153952
TI  - Neuroanatomic and cognitive abnormalities related to herpes simplex virus type 1
      in schizophrenia.
AB  - Herpes simplex virus 1 (HSV-1) tends to replicate in the temporal cortex and can
      damage the limbic system. The presence of serum antibodies to HSV-1 is associated
      with cognitive impairment in adults with schizophrenia, suggesting that cerebral
      gray matter abnormalities might distinguish patient subgroups defined by HSV-1
      exposure. We assessed 43 adult outpatients with schizophrenia. The assessment
      included clinical interviews, neurocognitive testing, anatomic brain magnetic
      resonance imaging and measures of serum IgG antibodies specific to herpes simplex
      viruses 1 and 2. We then compared 25 patients who tested positive for antibodies
      to HSV-1 with 15 who were seronegative for both HSV-1 and HSV-2. The seropositive
      patients performed significantly worse than the seronegative patients on four
      neuropsychological measures of psychomotor speed, executive functioning, and
      explicit verbal memory. Voxel-based morphometric analyses revealed that the same
      patients showed reduced gray matter volume in the anterior cingulate and areas of
      the cerebellum. Finally, performance on the test of psychomotor speed and
      executive functioning that showed the largest between- group effect size
      correlated with reduced gray matter volume in some of the same brain regions
      (cingulate and cerebellum) that distinguished the two HSV-1 subgroups. In these
      outpatients with schizophrenia, HSV-1 seropositivity and performance on a
      cognitive test that is highly sensitive to it co-localize to closely overlapping
      brain regions.

PMID- 20153953
TI  - Co-occurrence of neurodevelopmental genes in etiopathogenesis of autism and
      schizophrenia.

PMID- 20153954
TI  - Time-to-pregnancy and risk of schizophrenia.
AB  - Schizophrenia has been linked to advanced paternal age, but the explanation is
      unknown. We questioned whether the incidence of schizophrenia would be related to
      male reproductive capacity, as reflected in the time taken to conceive. We
      measured the incidence of schizophrenia in relation to time to conception in a
      sub-group of 12,269 in the Jerusalem cohort whose mothers, interviewed post
      partum, reported that the pregnancy had been intended. Compared with those
      conceived in less than 3 months, the unadjusted relative risks (RR) of
      schizophrenia associated with conception-waits of 3-5, 6-11 and 12+ months were
      1.10 (95% confidence interval, 0.62-1.94), 1.41 (0.79-2.52) and 1.88 (1.05-3.37)
      with p for trend=0.035. This trend was attenuated somewhat by adjusting for
      paternal age, and was observed more strongly in offspring of fathers aged 30+
      (p=.010). These findings suggest that factors associated with fecundability,
      either male or female, may contribute to the risk of schizophrenia.

PMID- 20153955
TI  - Iron/ethylcellulose (core/shell) nanoplatform loaded with 5-fluorouracil for
      cancer targeting.
AB  - Even though 5-fluorouracil has been demonstrated to display antitumor activity
      against a wide variety of cancers, high doses are needed to bring out the
      required therapeutic activity that could simultaneously lead to severe side
      effects. We hypothesized that the efficient delivery of 5-fluorouracil to tumors
      using a magnetic nanoplatform could reduce the dose required to obtain sufficient
      anticancer response. Thus, we have formulated a 5-fluorouracil-loaded magnetic
      nanomedicine consisting of a magnetic core (iron) and a biocompatible polymeric
      shell (ethylcellulose). These core/shell nanoparticles were synthesized by an
      emulsion solvent evaporation process, and 5-fluorouracil loading was assayed by
      surface incorporation onto the preformed nanocomposites, and by drug
      incorporation into the magnetic colloid. The contributions of both the surface
      and the polymeric network to the overall drug loading were investigated by means
      of optical absorbance and electrophoretic mobility determinations. 5-Fluorouracil
      entrapment into the polymeric matrix yielded a higher drug loading and a slower
      drug release profile as compared with drug adsorption. These preliminary results
      suggest the potential of this stimuli-sensitive drug carrier for cancer
      targeting.

PMID- 20153956
TI  - A machine learning-based approach to prognostic analysis of thoracic
      transplantations.
AB  - OBJECTIVE: The prediction of survival time after organ transplantations and
      prognosis analysis of different risk groups of transplant patients are not only
      clinically important but also technically challenging. The current studies, which
      are mostly linear modeling-based statistical analyses, have focused on small sets
      of disparate predictive factors where many potentially important variables are
      neglected in their analyses. Data mining methods, such as machine learning-based
      approaches, are capable of providing an effective way of overcoming these
      limitations by utilizing sufficiently large data sets with many predictive
      factors to identify not only linear associations but also highly complex, non
      linear relationships. Therefore, this study is aimed at exploring risk groups of
      thoracic recipients through machine learning-based methods. METHODS AND MATERIAL:
      A large, feature-rich, nation-wide thoracic transplantation dataset (obtained
      from the United Network for Organ Sharing-UNOS) is used to develop predictive
      models for the survival time estimation. The predictive factors that are most
      relevant to the survival time identified via, (1) conducting sensitivity analysis
      on models developed by the machine learning methods, (2) extraction of variables
      from the published literature, and (3) eliciting variables from the medical
      experts and other domain specific knowledge bases. A unified set of predictors is
      then used to develop a Cox regression model and the related prognosis indices. A
      comparison of clustering algorithm-based and conventional risk grouping
      techniques is conducted based on the outcome of the Cox regression model in order
      to identify optimal number of risk groups of thoracic recipients. Finally, the
      Kaplan-Meier survival analysis is performed to validate the discrimination among
      the identified various risk groups. RESULTS: The machine learning models
      performed very effectively in predicting the survival time: the support vector
      machine model with a radial basis Kernel function produced the best fit with an
      R(2) value of 0.879, the artificial neural network (multilayer perceptron-MLP
      model) came the second with an R(2) value of 0.847, and the M5 algorithm-based
      regression tree model came last with an R(2) value of 0.785. Following the
      proposed method, a consolidated set of predictive variables are determined and
      used to build the Cox survival model. Using the prognosis indices revealed by the
      Cox survival model along with a k-means clustering algorithm, an optimal number
      of "three" risk groups is identified. The significance of differences among these
      risk groups are also validated using the Kaplan-Meier survival analysis.
      CONCLUSIONS: This study demonstrated that the integrated machine learning method
      to select the predictor variables is more effective in developing the Cox
      survival models than the traditional methods commonly found in the literature.
      The significant distinction among the risk groups of thoracic patients also
      validates the effectiveness of the methodology proposed herein. We anticipate
      that this study (and other AI based analytic studies like this one) will lead to
      more effective analyses of thoracic transplant procedures to better understand
      the prognosis of thoracic organ recipients. It would potentially lead to new
      medical and biological advances and more effective allocation policies in the
      field of organ transplantation.

PMID- 20153957
TI  - Gastroesophageal reflux disease and graft failure after lung transplantation.
AB  - In spite of advances in lung transplantation, the median survival after lung
      transplant remains less than 5 years, an outcome that is significantly worse than
      other solid organ transplants. Efforts to understand the unique hurdles faced in
      lung transplant have revealed gastroesophageal reflux disease (GERD) as a risk
      factor for ultimate graft failure. The link between GERD and chronic lung
      rejection parallels the association between GERD and other forms of lung disease
      such as idiopathic pulmonary fibrosis. Understanding how GERD predisposes to
      graft failure is an important issue as it may lead to therapies such as surgical
      correction that aim to lessen the exposure of the pulmonary epithelium to gastric
      contents. Here, we review the link between GERD and lung disease and discuss the
      preclinical and clinical studies that are starting to elucidate a mechanism for
      this association.

PMID- 20153959
TI  - Frameless single-session robotic radiosurgery of liver metastases in colorectal
      cancer patients.
AB  - INTRODUCTION: Due to advanced chemotherapy regimens, patients presenting with
      residual liver metastases of colorectal cancer (CRC) has increased. Surgery of
      residual metastases enhances overall survival, but surgical resection is often
      limited. Less invasive techniques have been invented to enhance local disease
      control. We investigated in a selected patient cohort local control of liver
      metastasis from CRC using robotic radiosurgery. METHODS AND MATERIALS: In this
      study patients with colorectal liver metastases were prospectively followed after
      having been treated with single-session radiosurgery using a robotic image-guided
      device and real-time tumour tracking. The primary end-point was local control
      (LC); secondary end-points were toxicity, progression-free survival (PFS) and
      overall survival (OS). Extrahepatic metastases were excluded using a whole body
      (PET-CT: positron emission tomography computed tomography). Follow up was done by
      liver MRI every 3 months post-treatment. RESULTS: Fourteen patients (median age
      65 years), with a total of 19 colorectal liver metastases were treated with 24 Gy
      in one fraction. Median follow up was 16.8 months. A one-year LC rate of 87% and
      a median PFS of 9.2 months were reached. DISCUSSION: Frameless robotic image
      guided radiosurgery with real-time tumour tracking as an effective treatment for
      patients with colorectal liver metastases. This technique enhances the
      possibilities of multidisciplinary oncological concepts.

PMID- 20153958
TI  - Genomic imprinting-an epigenetic gene-regulatory model.
AB  - Epigenetic mechanisms (Box 1) are considered to play major gene-regulatory roles
      in development, differentiation and disease. However, the relative importance of
      epigenetics in defining the mammalian transcriptome in normal and disease states
      is unknown. The mammalian genome contains only a few model systems where
      epigenetic gene regulation has been shown to play a major role in transcriptional
      control. These model systems are important not only to investigate the biological
      function of known epigenetic modifications but also to identify new and
      unexpected epigenetic mechanisms in the mammalian genome. Here we review recent
      progress in understanding how epigenetic mechanisms control imprinted gene
      expression.

PMID- 20153960
TI  - Pyrolysis and combustion of oil palm stone and palm kernel cake in fixed-bed
      reactors.
AB  - The main objective of this research was to investigate the main characteristics
      of the thermo-chemical conversion of oil palm stone (OPS) and palm kernel cake
      (PKC). A series of combustion and pyrolysis tests were carried out in two fixed
      bed reactors. The effects of heating rate at the temperature of 700 degrees C on
      the yields and properties of the pyrolysis products were investigated. The
      results from the combustion experiments showed that the burning rates increased
      with an increase in the air flow rate. In addition, the FLIC code was used to
      simulate the combustion of the oil palm stone to investigate the effect of
      primary air flow on the combustion process. The FLIC modelling results were in
      good agreement with the experimental data in terms of predicting the temperature
      profiles along the bed height and the composition of the flue gases.

PMID- 20153961
TI  - Effect of nitrogen sources and vitamins on ligninolytic enzyme production by some
      white-rot fungi. Dye decolorization by selected culture filtrates.
AB  - The effect of amino acids, complex nitrogen sources and vitamin addition on
      Trametes trogii, Trametes villosa and Coriolus versicolor var. antarcticus
      ligninolytic enzyme production, was evaluated. Dye decolorization by their
      culture filtrates was compared. Glutamic acid followed by peptone, were the best
      N sources for laccase and manganese peroxidase production. The three fungi
      produced two laccase isoenzymes (molecular weights from 38 up to 150 kDa); their
      pattern of production was not affected by medium composition. Although the
      response was not uniform, vitamin addition sometimes stimulated ligninolytic
      enzyme production, but never inhibited it. Thiamine induced manganese peroxidase
      production. T. trogii grown in glutamic acid produced culture filtrates with the
      highest laccase (188.3 U/ml) and manganese peroxidase activities (4.5 U/ml),
      rendering the best results in decolorization. These crude filtrates were able to
      decolorize in half hour (at pH 4.5, 30 degrees C): 13%, 23%, 40%, 46%, 82%, 94%
      and 95% of Gentian Violet, Xylidine, Congo Red, Malachite Green, Remazol
      Brilliant Blue R, Indigo Carmine and Anthraquinone Blue, respectively.

PMID- 20153962
TI  - Extraction optimization and in vivo antioxidant activities of exopolysaccharide
      by Morchella esculenta SO-01.
AB  - Response surface methodology was used to optimize extraction parameters for
      Morchella esculenta SO-01 exopolysaccharide (EPS) produced during submerged
      culture. The optimum conditions for EPS extraction were predicted to be,
      concentration at 84.07 degrees C, precipitation for 22.19 h and pH 8.44, and EPS
      production was estimated at 5.45 g/L. The actual yield of EPS under these
      conditions was 5.32 g/L. The antioxidant capacity of the EPS was measured in vivo
      after filling the stomach with different doses of EPS and results showed that the
      activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of
      blood, spleen, liver, heart, and kidney were increased by 125%, 46.11%, 23.33%,
      12.19%, 41.29%, and 63.24%, 63.12%, 166.54%, 98.01%, 57.68%, respectively, and
      that malonaldehyde (MDA) of blood, spleen, liver, heart, and kidney were
      decreased by 21.80%, 67.84%, 28.48%, 56.15%, 41.62%. The results provide a
      reference for large-scale extraction of EPS by M. esculenta SO-01 in industrial
      fermentation.

PMID- 20153963
TI  - Synthesis and evaluation of 2-pyridylbenzothiazole, 2-pyridylbenzoxazole and 2
      pyridylbenzofuran derivatives as 11C-PET imaging agents for beta-amyloid plaques.
AB  - The syntheses and SAR of new series of beta-amyloid binding agents are reported.
      The effort to optimize signal-to-background ratios for these ligands are
      described. Compounds 8, 21 and 30 displayed desirable lipophilicity and
      pharmacokinetic properties. Compounds 8 and 21 were evaluated with in vitro
      autoradiographic studies and in vivo in APP/PS1 transgenic mice. It is shown that
      it was possible to increase the signal-to-background ratios compared to PIB 1, as
      demonstrated by compounds 8 and 21.

PMID- 20153964
TI  - Substituted fused bicyclic pyrrolizinones as potent, orally bioavailable hNK1
      antagonists.
AB  - Previous work on human NK(1) (hNK(1)) antagonists in which the core of the
      structure is a 5,5-fused pyrrolizinone has been disclosed. The structural
      activity-relationship studies on simple alpha- and beta-substituted compounds of
      this series provided several potent and bioavailable hNK(1) antagonists that
      displayed excellent brain penetration as observed by their good efficacy in the
      gerbil foot-tapping (GFT) model assay. Several of these compounds exhibited 100%
      inhibition of the foot-tapping response at 0.1 and 24h with ID(50)'s of less than
      1 mpk. One particular alpha-substituted compound (2b) had an excellent
      pharmacokinetic profile across preclinical species with reasonable in vivo
      functional activity and minimal ancillary activity.

PMID- 20153965
TI  - Becker muscular dystrophy patients with deletions around exon 51; a promising
      outlook for exon skipping therapy in Duchenne patients.
AB  - Theoretically, 13% of patients with Duchenne muscular dystrophy may benefit from
      antisense-mediated skipping of exon 51 to restore the reading frame, which
      results in the production of a shortened dystrophin protein. We give a detailed
      description with longitudinal follow up of three patients with Becker muscular
      dystrophy with in-frame deletions in the DMD gene encompassing exon 51. Their
      internally deleted, but essentially functional, dystrophins are identical to
      those that are expected as end products in DMD patients treated with the exon 51
      skipping therapy. The mild phenotype encourages further development of exon 51
      skipping therapy.

PMID- 20153966
TI  - Cell cycle control of mammalian neural stem cells: putting a speed limit on G1.
AB  - The potential to increase unlimitedly in number and to generate differentiated
      cell types is a key feature of somatic stem cells. Within the nervous system,
      cellular and environmental determinants tightly control the expansion and
      differentiation of neural stem cells. Importantly, a number of studies have
      indicated that changes in cell cycle length can influence development and
      physiopathology of the nervous system, and might have played a role during
      evolution of the mammalian brain. Specifically, it has been suggested that the
      length of G1 can directly influence the differentiation of neural precursors.
      This has prompted the proposal of a model to explain how manipulation of G1
      length can be used to expand neural stem cells. If validated in non-neural
      systems, this model might provide the means to control the proliferation vs.
      differentiation of somatic stem cells, which will represent a significant advance
      in the field.

PMID- 20153967
TI  - Induced pulsation of a continuous-flow total artificial heart in a mock
      circulatory system.
AB  - BACKGROUND: We studied the hemodynamic effects of inducing an artificial pulse in
      a continuous-flow total artificial heart consisting of 2 axial-flow pumps in a
      mock circulatory system. METHODS: We varied the amplitude (maximum minus minimum
      speed), beat rate and systolic duration of the left pump, right pump or both.
      Mean left and right pump speeds were maintained at 11 and 8 krpm, respectively.
      Flow rates and arterial and filling pressures were measured in the systemic and
      pulmonary portions of the mock circulation. Pulse pressure, pulse flow,
      pulsatility index and surplus hemodynamic energy (SHE) were calculated. The
      percent change in mean left atrial pressure (LAP) during each induced pulsatility
      condition was compared with that observed during continuous flow. RESULTS:
      Systemic pulse pressures of 17 to 61 mm Hg were attained when the left pump was
      pulsed, regardless of right pump pulsatility settings. The pulse pressure was
      directly related to the systolic duration and inversely related to the left pump
      beat rate. SHE ranged from 0.1 to 3.0 mm Hg, and its changes were comparable to
      those in pulse pressure. The LAP was reduced by left pump pulsation, but a
      maximal reduction (<or=77%) relative to continuous flow was achieved when the two
      pumps were copulsed or counterpulsed at a slow rate (10 bpm). CONCLUSIONS: This
      approach provided maximal flow pulsatility and an adequate reduction in LAP,
      which may be elevated in recipients of a cardiac replacement device. Further
      bench and in vivo experiments are needed to assess pump synchronization modes.

PMID- 20153969
TI  - Outcome following splenectomy in cats.
AB  - No studies have yet examined whether there are prognostic factors for survival
      for cats undergoing splenectomies. The medical records of 19 cats that had
      complete splenectomy were reviewed for information on preoperative,
      intraoperative, and postoperative factors. The most common presenting signs were
      a palpable abdominal mass in 58% and anorexia in 47% of the cats. Mast cell
      tumors were the most common reason for splenectomy and were found in 10/19 cats
      (53%); followed by hemangiosarcoma in 4/19 (21%); and lymphoma in 2/19 (11%). The
      Kaplan-Meier median survival time (MST) was 197 days, with a range from 2 days to
      1959 days. Three cats were noted to have preoperative weight loss, and this was
      the only factor that had prognostic significance for survival following surgery.
      For cats with weight loss the MST was 3 days, for cats with no weight loss noted
      the MST was 293 days (P=0.008).

PMID- 20153970
TI  - Attentional and perceptual impairments in Parkinson's disease with visual
      hallucinations.
AB  - Visual hallucinations (VH) are common in Parkinson's Disease (PD). Both deficits
      of perception and attention seem to play a role in the pathogenesis of VH in PD.
      However, the possible coexistence of impairments in attention and visual
      perception in PD with VH is not known. This study investigated both attention and
      visual perception in non-demented PD patients with VH, compared to PD patients
      without VH and healthy controls. Fourteen participants were included in each
      group. All patients were assessed with sustained visual attention and object and
      space perception tests. Only PD patients with VH showed impairments on object and
      space perception. In addition, PD patients with and without VH showed impairments
      on sustained visual attention, being more severely affected in PD patients with
      VH. Only in PD patients with VH sustained visual attention was associated with a
      decreased object and space perception. The results of our study thus suggest that
      in PD patients with VH an impairment of object and space perception, possibly in
      association with a decreased sustained visual attention, might play a role in the
      pathogenesis of VH.

PMID- 20153972
TI  - A methodology to enhance spatial understanding of disease outbreak events
      reported in news articles.
AB  - PURPOSE: The emergence and re-emergence of disease outbreaks of international
      concern in the last several years has raised the importance of health
      surveillance systems that exploit the open media for their timely and precise
      detection of events. However, one of the key barriers faced by current event
      based health surveillance systems is in identifying fine-grained terms for an
      outbreak's geographical location. In this article, we present a method to tackle
      this problem by associating each reported event with the most specific spatial
      information available in a news report. This would be useful not only for health
      surveillance systems, but also for other event-centered processing systems.
      METHODS: To develop an automated spatial attribute annotation system, we first
      created a gold standard corpus for training a machine learning model. Since the
      qualitative analysis on data suggested that the event class might have an impact
      on the spatial attribute annotation, we also developed an event classification
      system to incorporate event class information into the spatial attribute
      annotation model. To automatically recognize the spatial attribute of events,
      several approaches, ranging from a simple heuristic technique to a more
      sophisticated approach based on a state-of-the-art Conditional Random Fields
      (CRFs) model were explored. Different feature sets were incorporated into the
      model and compared. RESULTS: The evaluations were conducted on 100 outbreak news
      articles. Spatial attribute recognition performance was evaluated based on three
      metrics; precision, recall and the harmonic mean of precision and recall (F
      score). Among three strategies proposed in this article, the CRF model appeared
      to be the most promising for spatial attribute recognition with a best
      performance of 85.5% F-score (86.3% precision and 84.7% recall). CONCLUSION: We
      presented a methodology for associating each event in media outbreak reports with
      their spatial attribute at the finest level of granularity. Our goal has been to
      provide a means for enhancing the spatial understanding of outbreak-related
      events. Evaluation studies showed promising results for automatic spatial
      attribute annotation. In the future, we plan to explore more features, such as
      semantic correlation between words, that maybe useful for the spatial attribute
      annotation task.

PMID- 20153971
TI  - Genetic control of root development in rice, the model cereal.
AB  - Cereals possess a fibrous root system that is mainly composed of crown roots that
      emerge postembryonically from the nodes of the stem. Because the root system is
      not directly accessible and consequently difficult to study, it remains a target
      for breeders to improve the ability of plants to exploit the mineral and water
      resources of the soil. Breeding for root architecture necessitates identifying
      the genetic determinants of root development. This research is now underway in
      cereals, particularly in rice, the monocot model species. In this review, we
      examine recent data identifying genes that govern root development in cereals,
      such as ARL1/CRL1 in rice and RTCS in maize which encodes a conserved lateral
      organ boundary domain transcription factor involved in crown root initiation and
      development in response to auxin. Finally, we discuss the detection and
      validation of root development quantitative trait loci.

PMID- 20153973
TI  - Are hepatitis B virus "subgenotypes" defined accurately?
AB  - BACKGROUND: Recently, several novel hepatitis B virus (HBV) subgenotypes have
      been introduced that do not meet proper definition of "subgenotypes". In
      particular for HBV genotype A, such novel subgenotypes have been reported.
      OBJECTIVE: To comprehensively reanalyse all HBV subgenotypes A, and to propose a
      novel, consistent alternative for HBV classification. STUDY DESIGN: All HBV full
      length genome subgenotypes A1-A6 were reanalysed using phylogenetic
      reconstruction and genetic distance calculation in order to study their
      evolutionary relationships. RESULTS: Phylogenetic analysis based on the complete
      genome sequence of subgenotype A strains revealed four distinct clusters
      supported by high bootstrap values, whereas only the three groups A1, A2 and A6
      could be assigned as subgenotypes. Previously introduced subgenotype A3,
      "tentative A4" and A5 clustered together in one main branch and were designated
      as "quasi-subgenotypes". Also genetic distances failed to classify these three
      groups as definite subgenotypes. These results advocate for a new classification
      of HBV genotype A into subgenotype A1, A2, "quasi-subgenotype A3" and A4.
      CONCLUSION: Detailed phylogenetic analysis of the complete genome sequences
      demonstrates that some of available HBV genotype A strains may not be considered
      as definite "subgenotypes". These strains, which are mainly of African origin,
      could be considered as "quasi-subgenotypes" which puts them in between the
      "clade" and "subgenotype" definition. Geographical origin may have a key role in
      further classification of HBV subgenotypes.

PMID- 20153974
TI  - Detection and characterization of human parechoviruses in archived cell cultures,
      in Hungary.
AB  - BACKGROUND: Human parechoviruses (HPeV) belonging to the family Picornaviridae
      are widespread enteric pathogens and associated with various clinical symptoms in
      humans. OBJECTIVES: There is no report for detection of the circulating
      parechoviruses in Central Europe. The aim of this retrospective study was to
      detect and characterize human parechoviruses in cell cultures with "enterovirus"
      like cytophatic effect (CPE) archived between 1990 and 2000, in Hungary. STUDY
      DESIGN: Fecal samples from children with symptoms of gastroenteritis under age of
      10 were cultured as a previous routine diagnostic laboratory protocol for
      "enterovirus". Cell cultures indicating CPE were archived and deeply chilled (-80
      degrees C) from minimum 2 individuals (2-12 patients) in each year. Specimens
      were tested retrospectively, in 2009, for HPeV by reverse transcription-PCR (RT
      PCR) method using 5'UTR conserved primers. Specific primer pairs were designed to
      determine the complete nucleotide sequence of the structural region (VP0-VP3-VP1)
      of HPeV. RESULTS: Nine (9.1%) of 66 archived samples were found to be HPeV
      positive. Six (67%) samples were identified as HPeV1, 2 (22%) were HPeV4 and 1
      could not be determined. Three HPeV1 clusters were identified according to the
      isolation date originated from years 1990/1991, 1992/1995 and 1998. CONCLUSIONS:
      This is the first detection of human parechoviruses in Central Europe. Detection
      and genetic characterization of HPeV in available historical samples infected
      with previously unidentifiable agents with "enterovirus-like" cytopathogenic
      effect help to understand the genetic diversity and evolution of these viruses.

PMID- 20153975
TI  - Emergence of a genomic variant of the recombinant 2k/1b strain during a mixed
      Hepatitis C infection: a case report.
AB  - To date, few natural intergenotypic recombinant hepatitis C virus (HCV) strains
      have been characterized. A recombinant strain 2k/1b was detected for one HCV RNA
      positive individual who had just completed therapy for HCV 3a genotype infection.
      In the present report, five serum samples collected over the pre- and post
      treatment periods were used to investigate all the present HCV strains and the
      change over time of the infection pattern. Interestingly, the 2k/1b strain was
      already present during the genotype 3a infection and persisted during treatment.
      In the specimen collected three months post-treatment, two distinct strains,
      2k/1b and type 1, were found and then one 2k/1b strain in the subsequent ones. A
      genomic variant of the HCV RF1_2k/1b strain was identified. It was part of a
      mixed HCV infection and persisted and re-emerge after eradication of the dominant
      subtype 3a. This case indicates that HCV co-infection screening after relapse
      should be an alternative to explain the lack of response to treatment and the
      necessity to carefully study the epidemic spreading of this recombinant strain.

PMID- 20153976
TI  - HIV-1 elite controllers: beware of super-infections.
AB  - Super- and co-infection with HIV-1 are generally associated with accelerated
      disease progression. We report on the outcome of super-infection in two HIV-1
      infected individuals previously known as elite controllers. Both presented an
      acute retroviral syndrome following super-infection and showed an immuno
      virological progression thereafter. Host genotyping failed to reveal any of the
      currently recognized protective factors associated with slow disease progression.
      This report indicates that elite controllers should be informed of the risk of
      super-infection, and illustrates the complexity of mounting broad anti-HIV
      immunity.

PMID- 20153977
TI  - Serum nitrite and nitrate levels in children with obstructive sleep-disordered
      breathing.
AB  - BACKGROUND: Diminished nitric oxide (NO) levels have been reported in adults with
      obstructive sleep apnea but no data are available for children with obstructive
      sleep-disordered breathing (SDB). OBJECTIVES: To assess levels of serum NO
      metabolites in children with SDB and to explore the effects of NO metabolites,
      SDB and their interaction on blood pressure. METHODS: Morning nitrite, the sum of
      nitrite and nitrate (NO(x)), and the average of evening and morning blood
      pressure were assessed in children with SDB referred for polysomnography and in
      controls without SDB. RESULTS: Forty-three children with SDB (age: 5.8+/-2.1
      years) had moderate-to-severe nocturnal hypoxemia (SpO(2) nadir: 85.6+/-4%), 54
      subjects (6.6+/-2.7 years) had mild hypoxemia (SpO(2) nadir: 91.4+/-1.3%) and 20
      subjects were controls free of SDB (6.7+/-3.7 years). Subjects with moderate-to
      severe hypoxemia had significantly lower ln-transformed NO metabolites (1.4+/
      0.7, nitrites; 2.6+/-0.5, NO(x)) compared to those with mild hypoxemia (1.9+/
      0.8, nitrites; 3+/-0.6, NO(x)) and controls (2.2+/-0.7, nitrite; 3+/-0.6, NO(x);
      p<0.05). The effects of NO metabolites and SDB or their interaction on blood
      pressure were not significant (p>0.05). CONCLUSIONS: Moderate-to-severe hypoxemia
      accompanying SDB is associated with reduced concentrations of morning serum NO
      metabolites, but NO levels do not seem to affect blood pressure.

PMID- 20153978
TI  - Surviving childhood and reproductive-age malignancy: effects on fertility and
      future parenthood.
AB  - Annually, more than 50,000 cancer diagnoses are made in the USA in patients under
      the age of 35 years. Despite this staggering statistic, medical advancements have
      substantially improved survival rates. Thus, for both male and female patients
      with cancer, quality-of-life issues, such as fertility preservation and
      parenthood, have become an essential component of treatment. Unfortunately, many
      of the treatments to eradicate malignant processes can also compromise
      reproductive function. In these cases, fertility preservation should be discussed
      and initiated with early treatment planning, to allow the best chance for future
      parenthood, when appropriate. The effects of cancer and cancer treatments on
      fertility and future parenthood, including health risks for patients, their
      gametes, and offspring are discussed.

PMID- 20153979
TI  - Improving nurses' ability to identify anatomic location and leads on 12-lead
      electrocardiograms with ST elevation myocardial infarction.
AB  - BACKGROUND: ST segment elevation on the electrocardiogram (ECG) signifies
      complete occlusion of a coronary artery. Nurses play a significant role in
      obtaining, interpreting, and communicating 12-lead ECG findings. AIMS: We
      evaluate a hand held paper tool to determine if it assists nurses; (1) identify
      the presence of ST elevation myocardial infarction (STEMI), (2) location, and (3)
      leads. METHODS: A pre-test/post-test design was used. At pre-test, nurses from
      the emergency department (ED), coronary care unit (CCU), and the progressive care
      (PC) were given 6 patient scenarios (3 STEMI and 3 non-STEMI) and a corresponding
      12-lead ECG. This was followed by a brief in-service on how to use the hand held
      tool. The nurse then interpret the same six ECGs (in a different order) using the
      hand held tool. RESULTS: Seventy-five nurses participated. Identification of
      STEMI location improved when the tool was used. Lead identification improved in 2
      of the 3 STEMI scenarios. Overall, nurses' ability to correctly identify the 3
      non-ischemic ECGs was low, and in one ECG was lower when the tool was used.
      CONCLUSION: For ECGs with a STEMI pattern an easy-to-learn tool improves nurses'
      ability to identify STEMI location. Nurses require education for identifying ECG
      leads, and non-ischemic ECG patterns.

PMID- 20153980
TI  - Shaping of iNKT cell repertoire after unrelated cord blood transplantation.
AB  - Invariant natural killer T (iNKT) cells have a pivotal role in immune regulation,
      tumor surveillance, and the induction of allograft tolerance. In this report, we
      analyze the recovery of iNKT cells after unrelated cord blood transplantation
      (UCBT) of adult patients with high-risk acute myeloid leukemia. We found that
      iNKT cells were reconstituted within 1 month after UCBT, at the same time as NK
      cells and before conventional T cells. These iNKT cells displayed a unique
      primed/central memory CD4(+)CD45RO(+)CCR7(+)CD62L(+) phenotype soon after the
      transplant. Interestingly, the functional competence of these cells was poor,
      except for their high GM-CSF production capacity. However, this post-graft
      functionally immature state was transient and all of the patients tested had
      fully functional iNKT cells 3 to 6 months post-UCBT and high cytolytic capacity
      for destroying primary CD1d(+) myeloid blast cells. Our results raise the
      possibility that iNKT cells might play a key role in graft-versus-leukemia
      activity after UCBT.

PMID- 20153981
TI  - The effect of seizures on working memory and executive functioning performance.
AB  - The aim of this study was to assess whether duration of seizure disorder and
      lifetime seizure load are associated with deficits in higher cognitive functions
      in patients with temporal lobe epilepsy (TLE) (N=207) or psychogenic nonepileptic
      seizures (PNES) (N=216). Multivariate regression analyses revealed that age at
      onset, duration, and group assignment were significant predictors of
      neuropsychological performance (all P<or=0.02), with group having a moderating
      relationship. Univariate analyses revealed different patterns of predictor
      effects on cognitive functioning within each diagnostic group. An impairment
      index was calculated for each individual, and univariate analyses revealed that
      age at TLE but not PNES onset was the only significant predictor of impairment
      (b=-0.005, P<0.001). The results suggest that earlier age at seizure onset,
      longer duration, and higher lifetime seizure frequency affect cognitive
      functioning in both the TLE and PNES groups, but differently within each group.
      These results have implications for early diagnosis and intervention in both
      groups.

PMID- 20153982
TI  - Acute administration of docosahexaenoic acid increases resistance to
      pentylenetetrazol-induced seizures in rats.
AB  - OBJECTIVE: Docosahexaenoic acid (DHA), an omega-3 fatty acid, has been reported
      to raise seizure thresholds. The purpose of the present study was to test the
      acute anticonvulsant effects of unesterified DHA in rats, using the maximal
      pentylenetetrazol (PTZ) seizure model, and also to examine DHA incorporation and
      distribution into blood serum total lipids and brain phospholipids and
      unesterified fatty acids. Sedation was measured to monitor for the potential
      toxicity of DHA. METHODS: Male Wistar rats received subcutaneous injections of
      saline, oleic acid (OA), or DHA. An initial pilot study (Experiment 1)
      established 400mg/kg as an effective dose of DHA in the maximal PTZ seizure test.
      A subsequent time-response study, using 400mg/kg (Experiment 2), established 1
      hour as an effective postinjection interval for administering DHA subcutaneously.
      A final study (Experiment 3) comprised two different groups. The first group
      ("seizure-tested rats") received saline, OA, or DHA (400mg/kg) subcutaneously,
      and were seizure tested in the maximal PTZ test 1 hour later to confirm the
      seizure latency measurements at that time. The second group ("assay rats")
      received identical subcutaneous injections of saline, OA, or DHA (400mg/kg). One
      hour postinjection, however, they were sacrificed for assay rather than being
      seizure tested. Assays involved the analysis of serum and brain DHA. Sedation was
      measured in both Experiment 3 groups during the 1-hour period prior to seizure
      testing or sacrifice. RESULTS: As noted above, 400mg/kg proved to be an effective
      subcutaneous dose of DHA (Experiment 1), and 1 hour proved to be the most
      effective injection-test interval (Experiment 2). In Experiment 3, in the seizure
      tested animals, subcutaneous administration of 400mg/kg of DHA significantly
      increased latency to PTZ seizure onset 1 hour postinjection relative to the
      saline- and OA-injected controls, which did not differ significantly from each
      other (P>0.05). In the assay animals, no significant effects of treatment on
      blood serum total lipids or on brain phospholipid or unesterified fatty acid
      profiles (P>0.05) were observed. There were also no differences in sedation among
      the three groups (P>0.05). CONCLUSION: DHA increases resistance to PTZ-induced
      seizures without altering measures of sedation and, apparently, without changing
      DHA concentrations in serum or brain.

PMID- 20153983
TI  - Catatonia in encephalitis and nonconvulsive seizures: a case report and review of
      the literature.
AB  - A 20-year-old woman was admitted for psychosis. On further investigation, she was
      found to be have viral encephalitis and generalized nonconvulsive seizures. After
      the seizures were controlled, she remained in a prolonged catatonic state.
      Repeated intravenous benzodiazepine administration, improved her cognition
      dramatically. This case emphasizes that catatonia may occur after encephalitis
      and nonconvulsive seizures.

PMID- 20153985
TI  - Technical aspects and perspectives of the vaginal mold applicator for
      brachytherapy of gynecologic malignancies.
AB  - PURPOSE: The importance of the quality of cervical cancer brachytherapy
      applicators has been reported, suggesting a direct influence of competent
      technical implant performance on outcome. In our institute, an original
      brachytherapy technique based on the use of a molded applicator for genital tract
      brachytherapy has been applied routinely in clinical practice. Here, we report
      the technical aspects of this customized applicator and perspectives on its use.
      TECHNICAL ASPECTS: The first step consists of a vaginal impression that
      accurately shows the topography and extension of the tumor as well as the anatomy
      of the vagina and cervix. From this impression, an acrylic applicator is made.
      Then, the intended positions of the vaginal catheters are drawn on the surface of
      the mold by the radiation oncologist. Two plastic vaginal catheters are
      introduced and fixed on the internal surface of the molded applicator. A hole for
      the cervical os is made through which the uterine probe will be positioned.
      PERSPECTIVES: This method allows for high specificity within the framework of a
      modern brachytherapy procedure, integrating the tumor topography, anatomy of the
      patient, and internal movements of target and critical volumes. This technique
      has been successfully extended to other tumor locations, such as genital tract
      rhabdomyosarcoma in children and postoperative endocavitary brachytherapy in
      patients with endometrial cancer. CONCLUSION: Customization of a vaginal
      brachytherapy applicator allows for the maintenance of morphologic optimization
      throughout the treatment course, which better takes into account a fourth
      dimension: internal organ motion during the course of brachytherapy.

PMID- 20153984
TI  - Partial vs. whole breast irradiation in a community hospital: a retrospective
      cohort analysis of 200 patients.
AB  - PURPOSE: We compared patients undergoing partial breast irradiation (PBI) with
      the MammoSite applicator (Cytyc Corp., Marlborough, MA) to a similar group of
      patients who underwent whole breast irradiation with external beam radiotherapy.
      METHODS AND MATERIALS: Stage 0-IIA breast cancer patients satisfying American
      Brachytherapy Society selection criteria and receiving accelerated PBI with the
      MammoSite system (n=100) were compared for toxicities with similarly staged
      patients receiving whole breast irradiation using tangential portals (n=100). The
      MammoSite applicator treatment was prescribed to a total dose of 34 Gy. External
      beam doses generally ranged from 60 to 66 Gy. RESULTS: Based on common toxicity
      criteria scores for acute toxicities, MammoSite patients experienced less
      cutaneous toxicity, fatigue, and breast pain and had higher Karnofsky performance
      status scores during the acute period than external beam patients but experienced
      more seroma pain during followup. These results were both statistically
      significant and clinically meaningful. CONCLUSIONS: In our institutional
      experience, PBI using the MammoSite applicator produces less acute toxicity than
      external beam radiotherapy of the whole breast but is associated with an
      increased incidence of seroma pain. The rate of disease recurrence in both
      cohorts was low.

PMID- 20153986
TI  - The effects of adrenalectomy and autonomic blockades on the exercise tachycardia
      in conscious rats.
AB  - Heart rate (HR) during exercise is controlled by cardiac sympathetic (CSNA) and
      vagal (CVNA) efferent nerve activity and plasma catecholamines. To determine
      their relative contribution to the exercise tachycardia, we examined the effects
      of adrenalectomy (ADX) and autonomic blockades on the HR response during
      treadmill exercise for 32min in 13 conscious rats. The baseline HR was not
      influenced by ADX, suggesting no significant role of adrenal catecholamines on
      the baseline HR. Since the baseline HR was increased 61beats/min by atropine
      methyl nitrate (1.5mg/kg) and decreased 26beats/min by atenolol (3mg/kg), CVNA
      determined the baseline HR more than CSNA. ADX did not affect the immediate
      increase in HR at 0-12s from the exercise onset but reduced the subsequent
      increase in HR at 13-30s. These increases in HR at the early period of exercise
      were more blunted by atenolol than atropine. On the other hand, the peak
      tachycardia response of 99+/-8beats/min at the end of exercise, which was the
      same between the intact and ADX conditions, was blunted to 73% by atenolol, to
      77% by atropine, and to 35% by combined atenolol and atropine, respectively. In
      conclusion, it is likely that the tachycardia at the beginning of dynamic
      exercise is predominantly determined by the cardiac autonomic nerve activity,
      especially by a prompt increase in CSNA, and that the hormonal mechanism due to
      adrenal epinephrine contributes to a further increase in HR approximately in 13s
      from the onset of exercise.

PMID- 20153987
TI  - Simultaneous quantification of carteolol and dorzolamide in rabbit aqueous humor
      and ciliary body by liquid chromatography/atmospheric pressure chemical
      ionization mass spectrometry.
AB  - A rapid, sensitive and selective method for the simultaneous quantification of
      carteolol and dorzolamide in rabbit aqueous humor (AH) and ciliary body (CB) has
      been developed and validated using reversed phase-high performance liquid
      chromatography (RP-HPLC) with isocratic elution coupled with atmospheric pressure
      chemical ionization mass spectrometry/mass spectrometry (APCI-MS/MS). The
      analytes and nadolol (used as internal standard, IS) were purified from AH by
      protein precipitation. The sample preparation from CB was based on a two steps
      extraction procedure at different pH, utilizing a liquid-liquid extraction with a
      mixture of ethyl acetate, toluene and isopropanol 50:40:10 (v/v) at pH 8,
      followed by a second extraction with ethyl acetate at pH 11. The combined organic
      extracts were then back extracted into 0.1% aqueous trifluoroacetic acid (TFA).
      The accuracy and precision values, calculated from three different sets of
      quality control samples analyzed in sestuplicate on three different days, were
      within the generally accepted criteria for analytical methods (<15%). The assay
      proved to be accurate and precise when applied to the in vivo study of carteolol
      and dorzolamide in rabbit AH and CB after single administration of an eye drops
      containing both drugs.

PMID- 20153988
TI  - Identification and characterization of oxidation and deamidation sites in
      monoclonal rat/mouse hybrid antibodies.
AB  - Oxidation of methionine residues and deamidation of asparagine residues are the
      major causes of chemical degradation of biological pharmaceuticals. The mechanism
      of these non-enzymatic chemical reactions has been studied in great detail.
      However, the identification and quantification of oxidation and deamidation sites
      in a given protein still remains a challenge. In this study, we identified and
      characterized several oxidation and deamidation sites in a rat/mouse hybrid
      antibody. We evaluated the effects of the sample preparation on oxidation and
      deamidation levels and optimized the peptide mapping method to minimize oxidation
      and deamidation artifacts. Out of a total number of 18 methionine residues, we
      identified six methionine residues most susceptible to oxidation. We determined
      the oxidation rate of the six methionine residues using 0.05% H(2)O(2) at
      different temperatures. Methionine residue 256 of the mouse heavy chain showed
      the fastest rate of oxidation under those conditions with a half life of
      approximately 200 min at 4 degrees C and 27 min at 37 degrees C. We identified
      five asparagine residues prone to deamidation under accelerated conditions of pH
      8.6 at 37 degrees C. Kinetic characterization of the deamidation sites showed
      that asparagine residue 218 of the rat heavy chain exhibited the fastest rate of
      deamidation with a half live of 1.5 days at pH 8.6 and 37 degrees C. Analysis of
      antibody isoforms using free flow electrophoresis showed that deamidation is the
      major cause of the charged variants of this rat/mouse hybrid antibody.

PMID- 20153990
TI  - "But I Like My Body": Positive body image characteristics and a holistic model
      for young-adult women.
AB  - Extant body image research has provided a rich understanding of negative body
      image but a rather underdeveloped depiction of positive body image. Thus, this
      study used Grounded Theory to analyze interviews from 15 college women classified
      as having positive body image and five body image experts. Many characteristics
      of positive body image emerged, including appreciating the unique beauty and
      functionality of their body, filtering information (e.g., appearance commentary,
      media ideals) in a body-protective manner, defining beauty broadly, and
      highlighting their body's assets while minimizing perceived imperfections. A
      holistic model emerged: when women processed mostly positive and rejected
      negative source information, their body investment decreased and body evaluation
      became more positive, illustrating the fluidity of body image. Women reciprocally
      influenced these sources (e.g., mentoring others to love their bodies,
      surrounding themselves with others who promote body acceptance, taking care of
      their health), which, in turn, promoted increased positive source information.

PMID- 20153991
TI  - Revision reduction malarplasty with coronal approach.
AB  - BACKGROUND: Although reduction malarplasty is one of the most popular aesthetic
      surgical procedures in Asia, there have been a few reports of complications or
      unfavourable results. A poor understanding of the repositioning vector of the
      malar segment or improper fixation can result in unsatisfactory outcomes, such as
      non-union or inferolaterally displaced malunion of the malar complex. The authors
      present some revision malarplasty cases of patients with unfavourable or
      complicated outcomes to emphasise the importance of accurate repositioning and
      firm fixation of the malar complex in reduction malarplasty. METHODS: A total of
      20 patients underwent revision malarplasty by the coronal approach after an
      unfavourable primary reduction malarplasty. The major complaints included cheek
      drooping, depression, asymmetry and overcorrection. After repositioning the
      inferolaterally displaced malar complex to the appropriate position and obtaining
      bone-to-bone contact, rigid fixation was performed with a plate and screw. The
      calvarian bone was grafted to the bony gap. Midface and forehead lifts were also
      performed when indicated. RESULTS: Most patients had satisfactory results without
      severe complications. Two patients required a secondary revision due to asymmetry
      and non-union. Three patients developed frontal palsies, which were all
      temporary. CONCLUSION: Precise repositioning of the malar complex and firm
      fixation are essential for reduction malarplasty. The coronal approach is
      recommended when encountering unfavourable results or complications because it
      offers a wide surgical field for repositioning and fixation of the malar complex.

PMID- 20153992
TI  - Women's experiences when ultrasound examinations give unexpected findings in the
      second trimester.
AB  - BACKGROUND: In Norway pregnant women who are not regarded to be in a risk group
      are offered one routine ultrasound around the 18(th) week of pregnancy. If
      serious abnormalities are diagnosed, the women may apply for a termination.
      RESEARCH QUESTION: The aim of this study was to describe and understand some
      pregnant women's thoughts, feelings and dilemmas of choice when unexpected
      findings were diagnosed after a routine ultrasound examination. METHODS: This
      study was based on 22 semi-structured life world interviews. The women
      interviewed were informed of unexpected findings after undergoing routine
      ultrasound examinations around the 18(th) week of pregnancy. The analysis of the
      data was inspired by phenomenological research and followed the meaning
      condensation approach described by Kvale (1). RESULTS: The informants'
      experiences are presented by showing how they described shifts between juxtaposed
      emotional states: hope-acceptance, distancing-denial and grief-guilt. All of the
      informants described these swings between different emotions as a state of
      continuous chaos. DISCUSSION: The discovery of abnormality in a wanted child at a
      late stage of pregnancy can evoke an emotional crisis for women. All the
      informants in this study described swings between different emotions as being in
      a state of continuous chaos. The women had to make difficult choices regarding
      their own future and that of their child. CONCLUSION: Eliminating the anxiety and
      anguish experienced by women following a diagnosis of fetal abnormality is
      impossible. It must be possible, however, to mitigate their distress. Further
      research should develop methods to prepare women for coping in crises like these.

PMID- 20153989
TI  - Recent advances in the regulation of cholangiocyte proliferation and function
      during extrahepatic cholestasis.
AB  - Bile duct epithelial cells (i.e., cholangiocytes), which line the intrahepatic
      biliary epithelium, are the target cells in a number of human cholestatic liver
      diseases (termed cholangiopathies). Cholangiocyte proliferation and death is
      present in virtually all human cholangiopathies. A number of recent studies have
      provided insights into the key mechanisms that regulate the proliferation and
      function of cholangiocytes during the pathogenesis of cholestatic liver diseases.
      In our review, we have summarised the most important of these recent studies over
      the past 3 years with a focus on those performed in the animal model of
      extrahepatic bile duct ligation. In the first part of the review, we provide
      relevant background on the biliary ductal system. We then proceed with a general
      discussion of the factors regulating biliary proliferation performed in the
      cholestatic animal model of bile duct ligation. Further characterisation of the
      factors that regulate cholangiocyte proliferation and function will help in
      elucidating the mechanisms regulating the pathogenesis of biliary tract diseases
      in humans and in devising new treatment approaches for these devastating
      diseases.

PMID- 20153993
TI  - Prevalence of human papillomavirus infection among young women in North India.
AB  - BACKGROUND: The number of women infected with human papillomavirus (HPV) and the
      distribution of the HPV genotypes vary across populations and with age.
      OBJECTIVE: To determine the prevalence and genotype distribution of HPV in young
      married women aged 16-24 years. METHODS: 1300 women residing in an urban slum in
      Delhi donated samples of exfoliated cervical cells that were collected by the
      Digene((R)) kit and tested for the presence of HPV DNA by two techniques in
      parallel, i.e., PCR using PGMY consensus primers for all HPV types and the Digene
      HPV test (Hybrid Capture 2 (HC2) Probe B for high-risk (hr) types. Genotyping was
      done on all HPV positive samples using the Roche reverse line blot assay.
      RESULTS: HPV infection was detected in 91/1300 (7%) samples by PCR and 110/1300
      (8.4%) samples by HC2. Genotyping identified 20 high-risk and 11 low-risk types.
      HPV16 was the commonest high-risk type (3%) followed by HPV52 (1.2%) and HPV51
      (0.8%). Among low-risk types, HPV62 was the commonest (0.8%), followed by HPV84
      and HPV89 (0.5% each). Multiple infections were found in 3% of the HPV positive
      samples. CONCLUSION: A wide spectrum of HPV genotypes is seen in this young
      population. Knowledge about HPV types prevalent in communities in different
      regions of India would be useful in devising the optimum strategy for cervical
      cancer prevention.

PMID- 20153994
TI  - Uro-dermatological problems of a construction worker: paraaminobenzoic acid as a
      systemic photosensitizer.
AB  - A 51-year-old man suffered from an acute eczematous rash confined to the air- and
      light-exposed areas of the skin. As a construction worker he was exposed to
      common occupational allergens such as epoxy resins, but there was also remarkable
      holiday-associated sun exposure. He did not use any sunscreen agents. Several
      weeks before the onset of skin eruptions, conservative treatment of Peyronie's
      disease with oral PotabaTM (potassium paraaminobenzoate) had been started.
      Airborne contact dermatitis to volatile allergens was ruled out, while
      photopatchtesting revealed photoallergy to paraaminobenzoic acid (PABA). In
      sunscreens, PABA has mostly been abandoned due to its known topical
      photosensitization properties, but it has not yet been recognized as a systemic
      photosensitizer.

PMID- 20153995
TI  - Modulation of CD86 expression in skin dendritic cells does not always correlate
      with changes in DC motility, migration and allostimulatory functions.
AB  - CD86 expression is a well-known activation marker of dendritic cells (DC). In
      this study, we compared the level of CD86 expression in monocyte-derived skin DC
      with their motility, migratory abilities and allostimulatory capabilities. We
      show that motility and migration could be uncoupled from activation and that the
      immune response-modulating effects of certain compounds may correlate with down
      regulation of CD86 expression rather than with effects on motility and migration.

PMID- 20153996
TI  - Woolly hair with alopecia areata in a Caucasian girl.

PMID- 20153997
TI  - Melanoma under 18 years and pregnancy: report of three cases.
AB  - Melanoma is an uncommon tumour in childhood. Only isolated cases in pregnant
      patients younger than 18 years old have been previously described, therefore the
      biological behaviour of cutaneous melanoma in this group of age remains largely
      unknown. We report a single-institution experience with three patients who
      developed cutaneous melanoma before the age of 18 years and became pregnant
      concomitantly or during the course of the disease. High tumour thickness was
      attributed to later diagnosis and could be responsible for the aggressive
      biological behaviour in these patients. This delay was in part due to patients
      considering changes in nevi to be normal during pregnancy. The effect of
      pregnancy on the prognosis of patients with melanoma, particularly the role of
      hormonal and immunological factors on clinical outcome, survival and risk of
      developing metastases, as well as the differences between adolescent and adult
      populations are still controversial. Since there are no specific treatment
      strategies for this group of patients, treatment recommendations should be
      established according to adult experience.

PMID- 20153998
TI  - Gelatinases may play an important role in the progression of extramammary Paget's
      disease.

PMID- 20153999
TI  - [Molecular diagnosis and therapeutic measures in patients with dyskeratosis
      congenita].
AB  - Dyskeratosis congenita is a rare genetically heterogeneous disorder characterized
      by bone marrow failure and premature ageing. Current knowledge on clinical
      manifestations, molecular pathomechanisms, diagnostic criteria and therapeutic
      possibilities of patients with dyskeratosis congenita are described. Mutation
      analysis of the gene encoding for dyskerin revealed the c.IVS2-5C>G splice site
      mutation. The importance of early diagnosis in order to prevent severe invasive
      infections and non-infectious complications is emphasized. Family screening is
      important to identify carriers as prenatal genetic diagnosis conveys great
      benefits for family planning.

PMID- 20154000
TI  - [Prediction of the disease course in inflammatory bowel diseases].
AB  - Clinical presentation at diagnosis and disease course of both Crohn's disease
      (CD) and ulcerative colitis (UC) are heterogeneous and variable over time. During
      follow up, intestinal strictures or perforation may eventually develop at most
      patients with CD, and significant number of patients will undergo surgery. Much
      emphasis was laid in recent years on the determination of important predictive
      factors. Since early introduction of immunomodulators and/or biologicals might be
      justified in patients at risk for disease progression, so it is important to
      identify these patients as soon as possible. This review article summarizes the
      available literature on important clinical, endoscopic, fecal,
      serological/routine laboratory and genetic factors and hopefully will assist
      clinicians in the decision making of daily practice when choosing the treatment
      strategy for their patients with inflammatory bowel diseases.

PMID- 20154002
TI  - [Rockefeller fellows: Hungarian pathologists].

PMID- 20154001
TI  - [Women's knowledge about cervical cancer].
AB  - The human papillomavirus-infection is one of the most frequent sexually
      transmitted disease; it is detectable in nearly all cases of cervical cancer.
      Nowadays, the incidence of cervical cancer is unacceptable high. AIM: Our aim was
      to evaluate women's knowledge about the human papillomaviruses and cervical
      cancer. We tried to determine the possible connection between the higher
      mortality rates, the low participation rate of screenings and the knowledge about
      cervical cancer. METHODS: The related questionnaire contained 18 questions and
      was filled in by 422 women in certain cities and villages. The completed
      questionnaires were classified by age, place of residence, qualification,
      children in family, and human papillomavirus vaccination in anamnesis. RESULTS:
      The results showed that almost half of the women had a basic knowledge, but the
      number of correct answers to functional questions (e.g. "How can one decrease the
      risk of infection?") were less than it was expected according to the
      international literature. 56% of the women knew that the cervical cancer mainly
      caused by viruses, but only 17% of them named the right combination of the risk
      factors. The rate of correct answers was much lower in high school circles and
      42% of the women knew that males can be infected by human papillomaviruses. Only
      44% of them participate on cervical cancer screening once a year and 43% of them
      thought that cervical cancer and precancerous lesions do not mean serious risk
      and danger. 80% of the women knew that screening involves smear taking. The
      significance of knowledge level differences between groups was estimated by chi 2
      -probe. CONCLUSIONS: On the basis of the results, half of the women said to be
      familiar with the basic questions. In our opinion, it can be a beneficial
      consequence of educational campaigns. Although there were several issues, which
      were implemented by not more than 20% of correct answers.

PMID- 20154003
TI  - [Frigyes Karinthy and medicine].

PMID- 20154005
TI  - Closing plant stomata requires a homolog of an aluminum-activated malate
      transporter.
AB  - Plant stomata limit both carbon dioxide uptake and water loss; hence, stomatal
      aperture is carefully set as the environment fluctuates. Aperture area is known
      to be regulated in part by ion transport, but few of the transporters have been
      characterized. Here we report that AtALMT12 (At4g17970), a homolog of the
      aluminum-activated malate transporter (ALMT) of wheat, is expressed in guard
      cells of Arabidopsis thaliana. Loss-of-function mutations in AtALMT12 impair
      stomatal closure induced by ABA, calcium and darkness, but do not abolish either
      the rapidly activated or the slowly activated anion currents previously
      identified as being important for stomatal closure. Expressed in Xenopus oocytes,
      AtALMT12 facilitates chloride and nitrate currents, but not those of organic
      solutes. Therefore, we conclude that AtALMT12 is a novel class of anion
      transporter involved in stomatal closure.

PMID- 20154006
TI  - Dietary n-3 LCPUFA from fish oil but not alpha-linolenic acid-derived LCPUFA
      confers atheroprotection in mice.
AB  - The atheroprotective potential of n-3 alpha-linolenic acid (ALA) has not yet been
      fully determined, even in murine models of atherosclerosis. We tested whether ALA
      derived, n-3 long chain polyunsaturated fatty acids (LCPUFA) could offer
      atheroprotection in a dose-dependent manner. Apolipoprotein B (ApoB)100/100LDLr-/
      mice were fed with diets containing two levels of ALA from flaxseed oil for 16
      weeks. Fish oil- and cis-monounsaturated-fat-enriched diets were used as positive
      and negative controls, respectively. The mice fed cis-monounsaturated fat and ALA
      enriched diets exhibited equivalent plasma total cholesterol (TPC) and LDL
      cholesterol (LDL-c) levels; only mice fed the fish-oil diet had lower TPC and LDL
      c concentrations. Plasma LDL-CE fatty acid composition analysis showed that ALA
      enriched diets lowered the percentage of atherogenic cholesteryl oleate compared
      with cis-monounsaturated-fat diet (44% versus 55.6%) but not as efficiently as
      the fish-oil diet (32.4%). Although both ALA and fish-oil diets equally enriched
      hepatic phospholipids with eicosapentaenoic acid (EPA) and ALA-enriched diets
      lowered hepatic cholesteryl ester (CE) levels compared with cis-monounsaturated
      fat diet, only fish oil strongly protected from atherosclerosis. These outcomes
      indicate that dietary n-3 LCPUFA from fish oil and n-3 LCPUFA (mostly EPA)
      synthesized endogenously from ALA were not equally atheroprotective in these
      mice.

PMID- 20154008
TI  - A comparison of nephron number, glomerular volume and kidney weight in Senegalese
      Africans and African Americans.
AB  - BACKGROUND: Low nephron number is determined in utero and is a proposed risk for
      essential hypertension. Glomerular volume is inversely correlated with nephron
      number, and genetic and environmental factors that determine nephron number are
      thought to determine glomerular volume. This study compared total glomerular
      (nephron) number (N(glom)), mean glomerular volume (V(glom)) and kidney weight in
      two geographically separated black populations with significant common genetic
      ancestry. METHODS: Unbiased stereology was used to determine N(glom) and V(glom)
      in kidneys collected at coronial autopsy in an age- and sex-matched sample of 39
      adult Africans from Dakar in Senegal, West Africa and 39 African Americans from
      Mississippi in the USA. RESULTS: African Americans were taller and heavier than
      their Senegalese counterparts. N(glom) was remarkably similar-with a geometric
      mean of 937 967 in Senegalese and 904 412 in African Americans (P = 0.62).
      V(glom) was correlated inversely with N(glom) and directly with body surface area
      in both groups, but V(glom) was 54% greater in African Americans than in
      Senegalese Africans [8.30 +/- 2.92 (SD) and 5.38 +/- 1.25 microm(3) x 10(6),
      respectively] and remained significantly larger (38%) after adjustment for body
      size. V(glom) increased with age in African Americans, but not in the Senegalese.
      Kidney weight was larger in African Americans (P < 0.0001), but kidney-to-body
      weight ratio was not different between groups. CONCLUSIONS: Despite similar
      nephron numbers, a common genetic constitution, and even in relation to current
      body size, African Americans have larger V(glom) than Senegalese subjects. This
      may mark exposure to environmental stressors or hereditary traits concentrated in
      the population's relocation to North America.

PMID- 20154009
TI  - Cohort profile: Hlabisa HIV treatment and care programme.

PMID- 20154010
TI  - Gene function prediction from synthetic lethality networks via ranking on demand.
AB  - MOTIVATION: Synthetic lethal interactions represent pairs of genes whose
      individual mutations are not lethal, while the double mutation of both genes does
      incur lethality. Several studies have shown a correlation between functional
      similarity of genes and their distances in networks based on synthetic lethal
      interactions. However, there is a lack of algorithms for predicting gene function
      from synthetic lethality interaction networks. RESULTS: In this article, we
      present a novel technique called kernelROD for gene function prediction from
      synthetic lethal interaction networks based on kernel machines. We apply our
      novel algorithm to Gene Ontology functional annotation prediction in yeast. Our
      experiments show that our method leads to improved gene function prediction
      compared with state-of-the-art competitors and that combining genetic and
      congruence networks leads to a further improvement in prediction accuracy.

PMID- 20154011
TI  - Surface area accounts for the relation of gray matter volume to reading-related
      skills and history of dyslexia.
AB  - It is unknown whether the abnormalities in brain structure and function observed
      in dyslexic readers are congenital or arise later in development. Analyzing the 2
      components of gray matter volume separately may help in differentiating these
      possibilities. Gray matter volume is the product of cortical surface area,
      determined during prenatal brain development, and cortical thickness, determined
      during postnatal development. For this study, 16 adults with a history of
      phonological dyslexia and 16 age- and gender-matched controls underwent magnetic
      resonance imaging and an extensive battery of tests of reading-related skills.
      Cortical surface area and gray matter volume measures of the whole brain, the
      inferior frontal gyrus, and the fusiform gyrus were similarly related to
      phonological skills and a history of dyslexia. There was no relationship between
      cortical thickness and phonological skills or history of dyslexia. Because
      cortical surface area reflects cortical folding patterns determined prenatally,
      this suggests that brain differences in dyslexia are rooted in early cortical
      development and are not due to compensatory changes that occur during postnatal
      development and would be expected to influence cortical thickness. This study
      demonstrates the importance of examining the separate components of gray matter
      volume when studying developmental abnormalities.

PMID- 20154012
TI  - Reactive mechanism of cognitive control system.
AB  - The prefrontal cortex (PFC) is thought to modulate the neural network state in
      favor of the processing of task-relevant sensory information prior to the
      presentation of sensory stimuli. However, this proactive control mechanism cannot
      always optimize the network state because of intrinsic fluctuation of neural
      activity upon arrival of sensory information. In the present study, we have
      investigated an additional control mechanism, in which the control process to
      regulate the behavior is adjusted to the trial-by-trial fluctuation in neural
      representations of sensory information. We asked normal human subjects to perform
      a variant of the Stroop task. Using functional magnetic resonance imaging, we
      isolated cognitive conflict at a sensory processing stage on a single-trial basis
      by calculating the difference in activation between task-relevant and task
      irrelevant sensory areas. Activation in the dorsolateral PFC (DLPFC) covaried
      with the neural estimate of sensory conflict only on incongruent trials. Also,
      the coupling between the DLPFC and anterior cingulate cortex (ACC) was tighter on
      high-sensory conflict trials with fast response. The results suggest that
      although detection of sensory conflict is achieved by the DLPFC, online
      behavioral adjustment is achieved by interactive mechanisms between the DLPFC and
      ACC.

PMID- 20154014
TI  - Generation of glutamatergic neurons from postnatal and adult subventricular zone
      with pyramidal-like morphology.
AB  - The mammalian subventricular zone (SVZ) contains progenitors derived from
      cerebral cortex radial glia cells, which give rise to glutamatergic pyramidal
      neurons during embryogenesis. However, during postnatal life, SVZ generates
      neurons that migrate and differentiate into olfactory bulb gamma-aminobutyric
      acid (GABA)ergic interneurons. In this work, we tested if SVZ cells are able to
      produce glutamatergic neurons if confronted with the embryonic cortical
      ventricular zone environment. Different from typical SVZ chain migration, cells
      from P9-P11 SVZ explants migrate into embryonic cortical slices individually,
      many of which radially oriented. An average of 82.5% of green fluorescent protein
      positive cells were immunolabeled for neuronal marker class III beta-tubulin.
      Invading cells differentiate into multiple morphologies, including a pyramidal
      like morphotype. A subset of these cells are GABAergic; however, about 28% of SVZ
      derived cells are immunoreactive for glutamate. Adult SVZ explants also give rise
      to glutamatergic neurons in these conditions. Taken together, our results
      indicate that SVZ can be a source of glutamatergic cortical neurons when
      submitted to proper environmental cues.

PMID- 20154019
TI  - Development of high-resolution molecular phase-contrast stereoscopic X-ray
      imaging for accurate cancer diagnostics.
AB  - A new high-resolution molecular phase-contrast stereoscopic X-ray imaging (PSXI)
      modality is under development. It is aimed at offering oncologists and
      radiologists a system solution to discover and locate early-stage cancers and to
      assess tumour characteristics and therapeutic responses. The method is primarily
      developed for clinical implementation of biologically optimised target-specific
      cancer therapy to maximise cure and improve quality of life of cancer patients.
      The investigations here indicate theoretically that it is possible to achieve
      high-resolution and high-contrast 3D medical imaging with the PSXI technique at
      relatively low dose, almost an order of magnitude lower than those used in
      conventional computed tomography (CT) imaging, depending on image resolution and
      contrast of interest. Unique features of this new molecular imaging modality will
      be discussed in comparison with currently available molecular imaging modalities,
      such as positron emission tomography-computed tomography and magnetic resonance
      spectroscopic imaging. Some challenging issues with respect to the possible use
      of nanotechnology with the new molecular imaging modality will also be discussed.

PMID- 20154013
TI  - Dissociable connectivity within human angular gyrus and intraparietal sulcus:
      evidence from functional and structural connectivity.
AB  - The inferior parietal lobule (IPL) of the human brain is a heterogeneous region
      involved in visuospatial attention, memory, and mathematical cognition. Detailed
      description of connectivity profiles of subdivisions within the IPL is critical
      for accurate interpretation of functional neuroimaging studies involving this
      region. We separately examined functional and structural connectivity of the
      angular gyrus (AG) and the intraparietal sulcus (IPS) using probabilistic
      cytoarchitectonic maps. Regions-of-interest (ROIs) included anterior and
      posterior AG subregions (PGa, PGp) and 3 IPS subregions (hIP2, hIP1, and hIP3).
      Resting-state functional connectivity analyses showed that PGa was more strongly
      linked to basal ganglia, ventral premotor areas, and ventrolateral prefrontal
      cortex, while PGp was more strongly connected with ventromedial prefrontal
      cortex, posterior cingulate, and hippocampus-regions comprising the default mode
      network. The anterior-most IPS ROIs, hIP2 and hIP1, were linked with ventral
      premotor and middle frontal gyrus, while the posterior-most IPS ROI, hIP3, showed
      connectivity with extrastriate visual areas. In addition, hIP1 was connected with
      the insula. Tractography using diffusion tensor imaging revealed structural
      connectivity between most of these functionally connected regions. Our findings
      provide evidence for functional heterogeneity of cytoarchitectonically defined
      subdivisions within IPL and offer a novel framework for synthesis and
      interpretation of the task-related activations and deactivations involving the
      IPL during cognition.

PMID- 20154020
TI  - Studies of patient doses in interventional radiological examinations.
AB  - In Russia, especially in big cities like St. Petersburg, the annual number of
      interventional radiological (IR) examinations for both diagnostic and treatment
      purposes is increasing continuously. However, IR examinations might involve high
      patient doses and even the risk of skin injures that should be prevented. In this
      study, the exposure of patients caused by these examinations was analysed.
      Methods for the estimation of the effective dose (risk reduction of stochastic
      effects) were proposed. Thresholds for kerma-area product values that correspond
      to the occurrence of skin injury are also given.

PMID- 20154021
TI  - Main features of the tomographic reconstruction algorithm OPED.
AB  - This paper discusses the advantages of both geometry of data required for the
      reconstruction algorithm, orthogonal polynomial expansion on disc (OPED), and
      polynomial structure of this algorithm. We show that this type of geometry is a
      result of special parameterisation used within the OPED formalism. The
      practicability of the OPED data geometry is discussed and it is shown that the
      data of such geometry can be acquired directly. A method of reducing typical
      artefacts by using the polynomial structure of the algorithm is summarised as
      well.

PMID- 20154022
TI  - Paediatric CT examinations in 19 developing countries: frequency and radiation
      dose.
AB  - The aims of this study were to investigate the frequency of computed tomography
      (CT) examinations for paediatric patients below 15 y of age in 128 CT facilities
      in 28 developing countries of Africa, Asia and Eastern Europe and to assess the
      magnitude of CT doses. Radiation dose data were available from 101 CT facilities
      in 19 countries. The dose assessment was performed in terms of weighted CT dose
      index (CTDI(w)), volume CT index and dose length product (DLP) for chest, chest
      (high resolution), lumbar spine, abdomen and pelvis CT examinations using
      standard methods. The results show that on average the frequency of paediatric CT
      examinations was 20, 16 and 5 % of all CT examinations in participating centres
      in Africa, Asia and Eastern Europe, respectively. Eleven CT facilities in six
      countries were found to use adult CT exposure parameters for paediatric patients,
      thus indicating limited awareness and the need for optimisation. CT images were
      of adequate quality for diagnosis. The CTDI(w) variations ranged up to a factor
      of 55 (Africa), 16.3 (Asia) and 6.6 (Eastern Europe). The corresponding DLP
      variations ranged by a factor of 10, 20 and 8, respectively. Generally, the
      CTDI(w) and DLP values in Japan are lower than the corresponding values in the
      three regions in this study. The study has indicated a stronger need in many
      developing countries to justify CT examinations in children and their
      optimisation. Awareness, training and monitoring of radiation doses is needed as
      a way forwards.

PMID- 20154023
TI  - Wide dissemination of OXA-23-producing carbapenem-resistant Acinetobacter
      baumannii clonal complex 22 in multiple cities of China.
AB  - OBJECTIVES: In this study, multilocus sequence typing (MLST) was used to describe
      the genetic backgrounds of carbapenem-resistant Acinetobacter baumannii (CRAB)
      and carbapenem-susceptible A. baumannii (CSAB) from multiple cities of China.
      METHODS: One hundred and fifty-two CRAB and 74 CSAB isolates obtained from 16
      cities of China were selected for molecular characterization by MLST. eBURST was
      used to cluster sequence types (STs) into clonal complex (CCs) and infer
      evolutionary descent. PCR was used to detect carbapenemase-encoding genes and
      bla(AmpC) with the upstream element ISAba1. RESULTS: CSAB showed more diverse
      genetic backgrounds than CRAB since 36 distinct STs were identified in CSAB while
      only 8 STs were identified in CRAB. ST22 and its three single-locus variants, all
      clustered into CC22, were the most prominent STs, accounting for 86.8% of CRAB
      and 45.9% of CSAB, distributed in all 16 cities and possessing more noticeable
      antibiotic resistance than other STs. PCR amplification was positive for bla(OXA
      23) in most CRAB isolates but negative in CSAB isolates. The presence of ISAba1
      upstream of bla(AmpC) was variable in distinct STs of CRAB. eBURST reveals that
      CC22 is the largest group in the Pubmlst database, which also contains ST6
      previously identified in a European clone II isolate as a member of a subgroup of
      CC22. CONCLUSIONS: We describe the wide dissemination of CRAB CC22 in China. The
      close relatedness between CC22 and European clone II implies the probable global
      spread of CC22. It is inferred that ST22-CSAB evolves to ST22-CRAB through
      acquiring bla(OXA-23) as a determinative factor.

PMID- 20154024
TI  - Modelling response to HIV therapy without a genotype: an argument for viral load
      monitoring in resource-limited settings.
AB  - In the absence of widespread access to individualized laboratory monitoring,
      which forms an integral part of HIV patient management in resource-rich settings,
      the roll-out of highly active antiretroviral therapy (HAART) in resource-limited
      settings has adopted a public health approach based on standard HAART protocols
      and clinical/immunological definitions of therapy failure. The cost-effectiveness
      of HIV-1 viral load monitoring at the individual level in such settings has been
      debated, and questions remain over the long-term and population-level impact of
      managing HAART without it. Computational models that accurately predict
      virological response to HAART using baseline data including CD4 count, viral load
      and genotypic resistance profile, as developed by the Resistance Database
      Initiative, have significant potential as an aid to treatment selection and
      optimization. Recently developed models have shown good predictive performance
      without the need for genotypic data, with viral load emerging as by far the most
      important variable. This finding provides further, indirect support for the use
      of viral load monitoring for the long-term optimization of HAART in resource
      limited settings.

PMID- 20154025
TI  - Intermittent high glucose exacerbates the aberrant production of adiponectin and
      resistin through mitochondrial superoxide overproduction in adipocytes.
AB  - Hypoadiponectinemia and hyperresistinemia may be important in mediating signals
      from adipocytes to insulin-sensitive tissue and vasculature. However, the
      mechanism that mediates the aberrant production of adipokines remains poorly
      understood. In this study, we have investigated the effect of intermittent high
      glucose on the expression of adiponectin and resistin, and the production of 8
      hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine in the adipocytes, either in the
      presence or in the absence of Mn(III) tetrakis(4-benzoic acid) porphyrin chloride
      (MnTBAP) or thenoyltrifluoroacetone (TTFA). 3T3-L1 adipocytes were incubated for
      72 h in media containing different glucose concentrations: 5 mmol/l, 20 mmol/l, 5
      mmol/l alternating with 20 mmol/l glucose, with or without MnTBAP and TTFA. We
      measured the expression of resistin and adiponectin. The production of
      nitrotyrosine and 8-OHdG as oxidative stress parameter was measured. Both
      constant and intermittent high glucose significantly suppressed the expression
      and secretion of adiponectin, and increased expression and secretion of resistin
      in mature adipocytes compared to normal glucose conditions. However, these
      effects were significantly greater under intermittent high glucose conditions
      compared to constant high glucose. The levels of nitrotyrosine and 8-OHdG were
      significantly elevated under both intermittent and constant high glucose
      conditions, the effect being greater under intermittent high glucose. In
      addition, the antioxidants MnTBAP or TTFA reversed the aberrant production of
      adiponectin and resistin, as well as overproduction of nitrotyrosine and 8-OHdG
      in adipocytes induced by constant or intermittent high glucose. Intermittent high
      glucose exacerbates the aberrant production of adiponectin and resistin through
      reactive oxygen species overproduction at the mitochondrial transport chain level
      in adipocytes, indicating that glycemic variability has important pathological
      effects on the secretion of adipokines.

PMID- 20154026
TI  - Recycling waste brick from construction and demolition of buildings as pozzolanic
      materials.
AB  - This investigation elucidates the pozzolic characteristics of pastes that contain
      waste brick from building construction and demolition wastes. The TCLP leaching
      concentrations of waste brick for the target cations or heavy metals were all
      lower than the current regulatory thresholds of the Taiwan EPA. Waste brick had a
      pozzolanic strength activity index of 107% after 28 days. It can be regarded as a
      strong pozzolanic material. The compressive strengths of waste brick blended
      cement (WBBC) that contain 10% waste brick increased from 71.2 MPa at 28 days to
      75.1 MPa at 60 days, an increase of approximately 5% over that period. At 28
      days, the pozzolanic reaction began, reducing the amount of Ca(OH)(2) and
      increasing the densification. The intensity of the peak at 3640 cm(- 1)
      associated with Ca(OH)(2) is approximately the same for ordinary Portland cement
      (OPC) pastes. The hydration products of all the samples yield characteristics
      peaks at 978 cm(-1) associated with C-S-H, and at ~3011 cm(-1) and 1640 cm(-1)
      associated with water. The samples yield peaks at 1112 cm(-1), revealing the
      formation of ettringite. In WBBC pastes, the ratio Q(2)/Q(1) increases with
      curing time. These results demonstrate that increasing the curing time increases
      the number of linear polysilicate anions in C-S-H. Experimental results reveal
      that waste brick has potential as a pozzolanic material in the partial
      replacement of cement.

PMID- 20154028
TI  - Ethical issues in laboratory medicine.

PMID- 20154027
TI  - Npr2, yeast homolog of the human tumor suppressor NPRL2, is a target of Grr1
      required for adaptation to growth on diverse nitrogen sources.
AB  - Npr2, a putative "nitrogen permease regulator" and homolog of the human tumor
      suppressor NPRL2, was found to interact with Grr1, the F-box component of the
      SCF(Grr1) (Skp1-cullin-F-box protein complex containing Grr1) E3 ubiquitin
      ligase, by mass spectrometry-based multidimensional protein identification
      technology. Npr2 has two PEST sequences and has been previously identified among
      ubiquitinated proteins. Like other Grr1 targets, Npr2 is a phosphoprotein.
      Phosphorylated Npr2 accumulates in grr1Delta mutants, and Npr2 is stabilized in
      cells with inactivated proteasomes. Phosphorylation and instability depend upon
      the type I casein kinases (CK1) Yck1 and Yck2. Overexpression of Npr2 is
      detrimental to cells and is lethal in grr1Delta mutants. Npr2 is required for
      robust growth in defined medium containing ammonium or urea as a nitrogen source
      but not for growth on rich medium. npr2Delta mutants also fail to efficiently
      complete meiosis. Together, these data indicate that Npr2 is a phosphorylation
      dependent target of the SCF(Grr1) E3 ubiquitin ligase that plays a role in cell
      growth on some nitrogen sources.

PMID- 20154029
TI  - Filling the gaps in undergraduate teaching of clinical biochemistry.

PMID- 20154030
TI  - Histopathological reporting of pT4 tumour stage in colorectal carcinomas: dotting
      the 'i's and crossing the 't's.
AB  - A histological diagnosis of pT4 stage is used as the basis for offering adjuvant
      therapy to patients with colorectal cancer. Histological features diagnostic of
      pT4 stage in colorectal cancer include: (1) presence of tumour perforation, (2)
      invasion of an adjacent organ, (3) direct or discontinuous tumour extending to
      the non-peritonealised resection margin, and (4) tumour breaching the visceral
      peritoneum. Histological parameters to identify these features are not always
      entirely straightforward, making recognition of pT4 stage difficult at times. The
      presence of a cellular mesothelial reaction and/or inflammation extending to the
      serosal surface causes considerable confusion and may result in upstaging pT3
      tumours. Conversely, involvement of the non-peritonealised margin in colonic
      tumours other than rectal cancers is at a risk of being understaged. Audits have
      shown that significant differences remain in the frequency with which serosal
      involvement is found between individual pathologists and multidisciplinary teams.
      The recognition of the criteria that define pT4a and pT4b subsets in pT4 stage to
      highlight different therapeutic connotations is not universally accepted, and
      this is likely to affect future reporting of the subsets. The review article
      highlights the contentious issues in histopathological recognition of pT4 tumour
      stage based on microscopic parameters in colorectal cancer.

PMID- 20154031
TI  - Primary localised pleural neurofibroma: expanding the spectrum of spindle cell
      tumours of the pleura.
AB  - AIMS: Primary localised pleural neoplasms are a rare group of thoracic tumours,
      with solitary fibrous tumour representing the most frequently encountered entity.
      Two cases of localised pleural neurofibromas involving the pleura are described.
      METHODS AND RESULTS: The patients were both female: 78 and 29 years of age. In
      the former a pleural-based lesion was identified on a chest radiograph after she
      presented with shoulder pain. The second patient was known to have
      neurofibromatosis type I, and the pleural lesion was found incidentally during
      excision of a metastatic malignant peripheral nerve sheath tumour of the lung.
      Both tumours were localised and composed histologically of bland neoplastic
      spindle cells embedded in a loose collagenous matrix. There was variable
      immunoreactivity for S100 and CD34, while ultrastructure examination in the two
      cases showed a mixture of nerve sheath cell types. CONCLUSION: To the best of the
      authors' knowledge, localised neurofibromas have not been previously reported
      within the pleura. The presence of a bland spindle cell pleural neoplasm
      immunoreactive for CD34 may potentially be mistaken for a solitary fibrous
      tumour. While distinction is usually achieved on close attention to the
      histological features, staining with S100 protein, especially in small biopsies,
      should be considered to exclude a neurofibroma.

PMID- 20154032
TI  - Cardiac findings in leptospirosis.
AB  - BACKGROUND/AIM: In leptospirosis, although cardiac involvement in the form of ECG
      changes and myocarditis is known, it is not considered to be significant. This
      study analysed cardiac changes in leptospirosis. METHODS: Twenty-four hearts from
      patients who had died from leptospirosis were studied. Detailed gross and light
      microscopic examination was carried out. RESULTS: Myocarditis was noted in 96% of
      cases. Endocardial inflammation was seen in 50% of cases. This endocardial
      inflammation correlates with vasculitis, which is the principal pathogenetic
      mechanism of the disease. CONCLUSIONS: There is definite cardiac involvement in
      leptospirosis, which even though not symptomatically evident, may add to the
      morbidity or be contributory to the mortality associated with the disease. In
      addition, a possibility of dilated cardiomyopathy as a delayed consequence of
      severe myocarditis remains, and may need evaluation.

PMID- 20154033
TI  - Angiomatoid fibrous histiocytoma including cases with pleomorphic features
      analysed by fluorescence in situ hybridisation.
AB  - BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare soft-tissue tumour
      of uncertain differentiation and low metastatic potential. Cytogenetics and/or
      molecular genetics have revealed that most have a rearrangement of the EWSR1
      gene, whereas a FUS gene rearrangement is present in a minority of cases.
      Although some cases of AFH display striking pleomorphism and mitotic activity,
      there are no known clinical, morphological or genetic factors that predict
      metastasis. The authors present clinicopathological features of AFH, including
      cases showing a pleomorphic histological appearance, and results of fluorescence
      in situ hybridisation analysis of EWSR1 and FUS rearrangements. METHODS: Tumour
      samples from 10 patients were subjected to clinicopathological and
      immunohistochemical analysis and dual-colour fluorescence in situ hybridisation
      for EWSR1 and FUS with split-signal probes. RESULTS: All cases showed clinical
      features (sites: extremities followed by trunk; age: adolescent to young adult),
      morphology (multinodular proliferation of spindle cells, lymphoid cuffs and
      pseudovascular spaces) and immunohistochemical results (more than half were
      positive for CD68, CD99, desmin and epithelial membrane antigen) typical of AFH.
      There were two local recurrences in each of two patients. Two patients developed
      distant metastases and died from the disease; tumours of these two patients
      showed focal proliferation of large pleomorphic cells with hyperchromatic nuclei
      and high proliferative activity (>10/10 high-power field and Ki-67 labelling
      index >10%). There were no clinical, histological or immunohistochemical
      differences between the nine cases with EWSR1 rearrangement and one case with FUS
      rearrangement. CONCLUSIONS: Wide surgical excision and careful follow-up are
      necessary for patients with AFH in view of its risk of local recurrence and
      metastasis leading to a fatal outcome.

PMID- 20154034
TI  - The role of fine-needle aspiration in the diagnosis of thyroid lymphoma: a
      retrospective study of nine cases and review of published series.
AB  - AIMS: To review the clinicopathological, cytomorphological and immunophenotyping
      data from new cases and published series of thyroid lymphoma diagnosed by fine
      needle aspiration (FNA), in order to identify useful diagnostic features.
      METHODS: Cases from 1988 to 2009 with an FNA diagnosis of thyroid lymphoma were
      selected from hospital records. An electronic MEDLINE and EMBASE search retrieved
      published series from 1980 to 2009. Available clinical, cytomorphological and
      immunophenotyping data from all cases were collected. In our cases, cytology
      slides and available surgical specimens were also reviewed. RESULTS: There were
      nine cases from eight of our patients, and 70 reviewed cases from eight series
      with at least four patients each. The most common presentation was a rapidly
      enlarging thyroid mass. Average patient age was 61 years in reviewed cases and 72
      years in our cases. Large-cell lymphoma was the predominant subtype, revealing
      relatively monotonous populations of large, abnormal lymphoid cells. One of our
      cases, later diagnosed as marginal zone lymphoma, showed small lymphocytes with
      plasmacytoid features. Immunoprofiling information was available in five of our
      cases (three by immunocytochemistry and two by laser scanning cytometry) and in
      34 reviewed cases (22 by immunocytochemistry, six by flow cytometry, and six by
      flow cytometry or immunocytochemistry). CONCLUSIONS: Cytological diagnosis of
      thyroid lymphoma requires careful analysis of morphological, clinical and
      immunophenotypic information. The presented data suggest certain helpful
      features: a fast-growing nodule in an elderly patient, a monotonous population of
      large abnormal cells in a background of lymphoglandular bodies, a predominant
      population of plasmacytoid lymphocytes, and immunophenotyping demonstrating light
      chain restriction.

PMID- 20154035
TI  - Quick-multiplex-consensus (QMC)-PCR followed by high-resolution melting: a simple
      and robust method for mutation detection in formalin-fixed paraffin-embedded
      tissue.
AB  - BACKGROUND: Mutation detection in tumours will become increasingly important in
      pathological diagnosis as 'predictive' mutations are identified. A cheap and
      reliable test that works on formalin-fixed paraffin-embedded (FFPE) tissue is
      required. METHODS: The quick-multiplex-consensus (QMC)-PCR protocol was developed
      to be used with high-resolution melting (HRM) analysis. The assay was compared
      with Sanger sequencing. Robustness of the assay was tested in DNA from FFPE
      tissue. RESULTS: QMC-PCR with HRM could detect a minimum of 2.5% of mutant
      alleles (compared with 20% detectable for Sanger sequencing). Ten mutation
      hotspots in KRAS, BRAF, PIK3CA and CDC4 were screened in 29 cell lines with 100%
      sensitivity and specificity. Forty-three FFPE colorectal tumours were sequenced
      for hotspots in KRAS and PIK3CA and then screened by QMC-PCR. There was 100%
      sensitivity, although, of 21 mutations detected by QMC-PCR, 16 were confirmed by
      sequencing (71% specificity, positive predictive value 76%). All 43 samples were
      then screened for mutations in all 10 hotspots. Of 430 tests, 43 (10%) showed
      aberrant melting and 36 were confirmed mutant (positive predictive value 84%). As
      our technique is more sensitive than direct sequencing, the remaining seven tests
      are probably sequencing false-negatives. Precision tests showed that there was
      little intra-assay and interassay variation. CONCLUSIONS: QMC-PCR with HRM is a
      simple, robust and inexpensive technique which had greater sensitivity than
      Sanger sequencing. It allows multiple mutation hotspots to be rapidly screened
      and is thus highly suited to mutation detection in DNA derived from FFPE tissues.

PMID- 20154036
TI  - TCR-Vbeta flow cytometric analysis of peripheral blood for assessing clonality
      and disease burden in patients with T cell large granular lymphocyte leukaemia.
AB  - AIMS: T cell large granular lymphocytes (T-LGLs) are commonly increased in
      reactive conditions as well as T-LGL leukaemia. This differential diagnosis often
      requires a combined assessment of clonality and tumour burden. In this study we
      assessed the utility of flow cytometric (FC) analysis of T cell receptor beta
      chain variable region (TCR-Vbeta) expression by using 24 antibodies reactive to
      70% of the TCR-Vbeta repertoire. METHODS: Analyses were performed on peripheral
      blood samples obtained from 20 patients with a confirmed diagnosis of T-LGL
      leukaemia and 18 patients without known T cell lymphoproliferative diseases.
      RESULTS: The results were compared with TCR gene rearrangement status assessed by
      PCR. By FC analysis, 19/20 T-LGL leukaemia cases were CD3+CD8+ and one case was
      CD3+CD4+. All the cases demonstrated at least one immunophenotypic aberration,
      with altered CD5 expression being most frequent. Abnormal Vbeta expression was
      detected by FC in 19 of 20 (95%) T-LGL leukaemia cases, but in none of the
      controls; this showed 100% concordance with TCR gene rearrangement studies. In
      addition to establishing clonality, FC Vbeta analysis enables calculation of
      absolute numbers of clonal T cells; this is important in monitoring tumour burden
      after treatment. CONCLUSIONS: It is concluded that FC Vbeta analysis is a fast,
      reliable and quantitative method that can simultaneously assess T-LGL leukaemia
      clonality and tumour burden.

PMID- 20154037
TI  - Effect of hydroxyurea on the transfusion requirements in patients with severe HbE
      beta-thalassaemia: a genotypic and phenotypic study.
AB  - BACKGROUND: Haemoglobin E (HbE)-beta-thalassaemia has a very variable clinical
      presentation. The management of severe cases that are often transfusion dependent
      is similar to that of cases of beta-thalassaemia major; however, this is often
      not possible in India because of its high cost and the lack of availability of
      safe blood at many places. Thus there was a need for a drug such as hydroxyurea,
      which is known to reduce the transfusion requirements of patients with
      thalassaemia intermedia. This study was undertaken to evaluate the response of
      Indian patients with HbE-beta-thalassaemia to hydroxyurea. MATERIALS AND METHODS:
      11 patients with HbE-beta-thalassaemia receiving regular transfusion plus two
      less frequently transfused patients were selected for hydroxyurea therapy.
      Clinical and haematological evaluation was performed before and after treatment
      for 2 years. Molecular studies included beta-globin genotype, beta-globin gene
      haplotype, Xmn I polymorphism and alpha-genotyping. RESULTS: Four clinically
      severe patients became transfusion independent (responders) after hydroxyurea
      therapy, four patients showed a reduction in their transfusion requirements
      (partial responders), and three patients were non-responders. Responders showed a
      statistically significant increase in Hb, mean corpuscular volume, mean cell Hb,
      fetal Hb and F cells with a reduction in their transfusion requirements. A
      reduction in serum ferritin concentration was also seen in responders and non
      responders. CONCLUSIONS: Genetic markers such as Xmn I polymorphism and alpha
      gene deletions were not always beneficial for the response to hydroxyurea
      therapy. Thus many more markers and a larger cohort need to be studied to predict
      the response in these patients.

PMID- 20154038
TI  - Association between hypoparathyroidism and defective T cell immunity in 22q11.2
      deletion syndrome.
AB  - AIMS: Although poor thymic function leading to viral and fungal infections can be
      a feature of chromosome 22q11.2 deletion syndrome, most patients have relatively
      normal immunity. The aim of this study was to investigate which clinical and
      laboratory parameters best predict the likelihood of serious or recurrent
      infections in patients with this syndrome. METHODS: Clinical and laboratory
      parameters from 64 patients with 22q11.2 deletion syndrome referred to two
      immunology centres in the north of England were studied retrospectively. RESULTS:
      31 (48%) patients had no problems with infection, 21 (33%) had bacterial
      infections, and 12 (19%) had recurrent or persistent thrush and/or viral
      enteritis and bronchiolitis, the latter suggestive of a significant T cell
      immunodeficiency. Patients with a history of thrush/viral infections, but not
      those with bacterial infections, had significantly lower CD4+ and CD8+ T
      lymphocyte numbers (relative risk (95% CI) 0.3 (0.1 to 0.8)) and
      phytohaemagglutinin mitogen responses (0.4 (0.2 to 0.8)) adjusted for age at
      testing. Hypoparathyroidism was associated with low T lymphocyte numbers and
      function (p<0.05) as well as an increased risk of thrush/viral infections
      (p<0.0001) after adjusting for age at testing. CONCLUSIONS: 22q11.2 syndrome
      patients with hypoparathyroidism are more likely to have a clinically significant
      T cell immunodeficiency and lower laboratory parameters of T cell function, with
      a higher risk of thrush and viral bronchiolitis and enteritis. Measurement of
      absolute CD3 count is a simple and accurate predictor of fungal/viral infection
      risk, with phytohaemagglutinin mitogen responses providing little or no further
      value in most patients.

PMID- 20154039
TI  - Serum CA19.9 levels are commonly elevated in primary ovarian mucinous tumours but
      cannot be used to predict the histological subtype.
AB  - AIMS: CA19.9 is a monosialoganglioside secreted by mucinous tumours of the
      gastrointestinal tract, including the pancreas and biliary tree. Limited studies
      have shown that this tumour marker may also be elevated in primary ovarian
      mucinous neoplasms, but no study has assessed whether serum CA19.9 levels can be
      used to predict if a primary ovarian mucinous tumour is benign, borderline or
      malignant. The aim of this study was to correlate the serum CA19.9 level with the
      histological features in a large series of primary ovarian mucinous neoplasms.
      METHODS: 144 cases of primary ovarian mucinous neoplasm (79 benign, 45 borderline
      and 20 malignant) were identified in which a preoperative serum CA19.9 level had
      been performed. The association between the serum levels and the histological
      subtype and a variety of other parameters was investigated. In a subset of cases,
      immunohistochemical staining for CA19.9 was performed on tumour blocks. RESULTS:
      Serum CA19.9 levels were elevated in 27%, 38% and 40% of mucinous cystadenomas,
      borderline mucinous tumours and mucinous carcinomas, respectively. Markedly
      elevated levels of serum CA19.9 were observed in each group, with the highest
      serum CA19.9 measurements being noted in borderline mucinous tumours. There was
      no relationship between the serum CA19.9 level and whether the tumours were
      benign, borderline or malignant (Kruskal-Wallis test p value=0.32). A weak but
      statistically significant correlation was found between tumour maximum dimension
      and CA19.9 level (Spearman's rank correlation coefficient=0.17, p=0.04). In those
      cases in which CA19.9 immunohistochemistry was performed, all tumours showed
      positive staining for CA19.9, with 60% of these cases being associated with an
      elevated serum CA19.9 level. CONCLUSION: Preoperative CA19.9 levels cannot be
      used to predict whether a suspected ovarian mucinous tumour is benign, borderline
      or malignant. Markedly elevated serum levels (>1000 U/ml) may be found in benign
      mucinous neoplasms as well as in borderline and malignant tumours.

PMID- 20154040
TI  - Composite renal cell carcinoma with clear cell renal cell carcinomatous and
      carcinoid tumoral elements: a first case report.
AB  - Renal endocrine tumours are extremely rare, and carcinoid tumoral elements in
      renal cell carcinoma have never been reported. This is the first report of a
      composite renal cell carcinoma containing a clear cell renal cell carcinoma
      associated with carcinoid tumoral elements, in a patient with synchronous
      metastatic disease. In the absence of specific radiological and clinical
      manifestations, typical morphological features as well as an immunostaining
      profile of neuroendocrine differentiation were identified by microscopy.
      Secondary nodal and liver localisations were characterised by carcinoid elements
      only. Despite antiangiogenic therapy, liver metastasis progressed, suggesting
      that adjuvant therapy cannot be based on the presence of the clear cell renal
      cell carcinoma component. In this context, extensive tissue sampling is
      recommended to reveal the endocrine component that is the most aggressive element
      of such a composite carcinoma.

PMID- 20154041
TI  - Leiomyoma of the gallbladder: a case report with review of the literature and
      discussion of the differential diagnosis.
AB  - Mesenchymal neoplasms of the gallbladder are rare, and most represent sarcomas of
      various histological types. To our knowledge, only a few patients with multiple
      Epstein-Barr virus (EBV)-associated smooth muscle tumours of the gallbladder in
      the setting of immunodeficiency have been reported in the English literature, but
      no single case of conventional leiomyoma has been well documented to date. A case
      of gallbladder leiomyoma in a healthy 34-year-old woman is described here. The
      tumour was found incidentally on a routine ultrasound examination and was removed
      by simple cholecystectomy. The patient is alive and well at last follow-up, 6
      months after surgery. Histology and immunohistochemistry were consistent with a
      benign smooth muscle neoplasm that is very similar to conventional uterine
      leiomyoma. The tumour was negative for both EBV-encoded nuclear RNAs and EBV
      latent membrane antigen. The patient had no history of uterine leiomyoma or other
      neoplasms or clinical evidence of an immune defect. Leiomyoma should be included
      in the differential diagnosis of spindle cell tumours of the gallbladder and must
      be distinguished from leiomyosarcoma and the rare gastrointestinal stromal tumour
      like neoplasms reported recently at this unusual anatomical site.

PMID- 20154042
TI  - A meningeal myofibroblastic neoplasm related to solitary fibrous tumour and
      associated with a malignant neuroblastic element.
AB  - BACKGROUND: Solitary fibrous tumour (SFT) is a rare mesenchymal tumour now
      described at many locations, including the meninges. Intracranial SFT closely
      resembles meningioma clinically and radiologically, and, like meningioma, reports
      of meningeal SFT suggest a relatively benign behaviour after complete resection.
      Histopathological features distinguishing SFT from meningioma include variable
      cellularity, spindle cells arranged in fascicles, staghorn blood vessels and
      immunopositivity for CD34. CLINICAL PRESENTATION: The case is reported of a 60
      year-old man with an anterior cranial fossa meningeal-based mass, which was
      resected. Histology showed some features in common with SFT (variable
      cellularity, spindled morphology, CD34 expression), but included an epithelioid
      element with cytokeratin and desmin immunopositivity, and lacked the
      characteristic vascular pattern of SFT. Histological features of meningioma were
      lacking. Recurrence of the tumour with extracranial extension 9 years later
      resulted in death of the patient. Histological examination revealed similar
      biphasic epithelioid and spindled CD34-immunopositive appearance to the earlier
      tumour, but in addition showed a high-grade element resembling olfactory
      neuroblastoma. CONCLUSION: This case report is of a meningeal-based mesenchymal
      neoplasm with histological similarities to SFT. Its morphology and
      immunophenotype, however, are distinct from SFT and hence it is proposed that it
      is a newly described entity. In addition, recurrence of the tumour with a high
      grade neuroblastic element has, to our knowledge, not previously been described
      in SFT.

PMID- 20154043
TI  - Calculi and intracellular ochronosis in the submandibular tissues from a patient
      with alkaptonuria.
AB  - Alkaptonuria (AKU) is a rare autosomal recessive condition caused by deficiency
      of the enzyme homogentisate 1,2 dioxygenase, resulting in widespread deposition
      of oxidised homogentisic acid (HGA) polymer, primarily in joint tissues but also
      in other connective tissues. Macroscopic pigmentation of connective tissues in
      AKU is well documented and is the end point of a process that is not understood.
      Deposition in less common regions may provide clues to the pigment formation
      process. This is the first report of detection of ochronotic pigment in acinar
      cells and lumina in the submandibular gland of a patient with AKU. Deposition was
      noted in the apical region of the cells. A lobar duct presented a large calculus
      with unusual deposits possibly associated with calcium salts. This report
      highlights the effect that local and intracellular factors may have on converting
      HGA into polymeric derivatives in the absence of an extracellular matrix.

PMID- 20154050
TI  - Acute cough in adults.

PMID- 20154049
TI  - Short term and intermediate term comparison of endarterectomy versus stenting for
      carotid artery stenosis: systematic review and meta-analysis of randomised
      controlled clinical trials.
AB  - OBJECTIVE: To evaluate the relative short term safety and intermediate term
      efficacy of carotid endarterectomy versus carotid artery stenting. DESIGN:
      Systematic review and meta-analysis. DATA SOURCES: BIOSIS, Embase, Medline, the
      Cochrane central register of controlled trials, International Pharmaceutical
      Abstracts database, ISI Web of Science, and Google scholar and bibliographies,
      from 1 January 1990 to 25 July 2009. STUDY SELECTION: Randomised controlled
      trials comparing carotid endarterectomy with carotid artery stenting in patients
      with carotid artery stenosis with or without symptoms. DATA EXTRACTION: Primary
      end point was a composite of mortality or stroke. Secondary end points were
      death, stroke, myocardial infarction, or facial neuropathy (as individual end
      points), and mortality or disabling stroke (as a composite end point). DATA
      SYNTHESIS: 11 trials were included (4796 patients); 10 reported on short term
      outcomes (n=4709) and nine on intermediate term outcomes (1-4 years). The
      periprocedural risk of mortality or stroke was lower for carotid endarterectomy
      (odds ratio 0.67, 95% confidence interval 0.47 to 0.95; P=0.025) than for carotid
      stenting, mainly because of a decreased risk of stroke (0.65, 0.43 to 1.00;
      P=0.049), whereas the risk of death (1.14, 0.56 to 2.31; P=0.727) and the
      composite end point mortality or disabling stroke (0.74, 0.53 to 1.05; P=0.088)
      did not differ significantly. The odds of periprocedural myocardial infarction
      (2.69, 1.06 to 6.79; P=0.036) or cranial nerve injury (10.2, 4.0 to 26.1;
      P<0.001) was higher in the carotid endarterectomy group than in the carotid
      stenting group. In the intermediate term, the two treatments did not differ
      significantly for stroke or death (hazard ratio 0.90, 95% confidence interval
      0.74 to 1.1; P=0.314). CONCLUSIONS: Carotid endarterectomy was found to be
      superior to carotid artery stenting for short term outcomes but the difference
      was not significant for intermediate term outcomes; this difference was mainly
      driven by non-disabling stroke. Significantly fewer cranial nerve injuries and
      myocardial infarctions occurred with carotid artery stenting.

PMID- 20154051
TI  - Carotid artery stenosis.

PMID- 20154053
TI  - Behavioral norms for condensed moral vignettes.
AB  - Moral judgment is an evaluation of the actions and character of a person made
      with respect to societal norms. Although many types of vignettes have been used
      in previous studies on moral beliefs and judgment, what is missing is a set of
      standardized common vignettes based in real life. The goal of this study was to
      provide researchers with stimuli that have values on several dimensions
      pertaining to moral judgment and whose underlying components are known. These
      values will allow researchers to select stimuli based on standardized ratings
      rather than on the results of pilot studies, while avoiding the limitations of
      the classic, abstract moral scenarios. Our study was composed of three phases,
      (i) collecting and shortening the vignettes, (ii) obtaining ratings of the
      vignettes on several dimensions including emotional intensity, degree of social
      norm violation, and level of harm or benefit caused and (iii) determining the
      underlying components of the vignettes by performing a factor analysis. We found
      three components that accounted for most of the variance: norm violation, social
      affect and intention. The resulting vignettes can be used in future parametric
      studies on moral judgment in behavioral, neuropsychological and functional
      imaging experiments.

PMID- 20154054
TI  - Attentional and executive dysfunction as predictors of smoking within the
      Childhood Cancer Survivor Study cohort.
AB  - INTRODUCTION: Previous research has suggested that childhood cancer survivors
      initiate smoking at rates approaching those of healthy individuals, even though
      smoking presents unique risks to survivors. The present study explores whether
      the attentional and executive functioning (EF) deficits associated with cancer
      and treatment place survivors of childhood cancer at increased risk for smoking.
      METHODS: Data from the Childhood Cancer Survivor Study were examined to identify
      concurrent and longitudinal correlates of tobacco use. We explored whether
      childhood attention problems and adulthood executive dysfunction were associated
      with smoking among adult survivors of childhood cancer. RESULTS: Childhood
      attention problems emerged as a striking predictor of adult smoking nearly a
      decade later on average. Nearly half (40.4%) of survivors who experienced
      attention problems in childhood reported a history of smoking, a significantly
      higher rate of ever smoking, than reported by those without childhood attention
      problems (relative risk [RR] = 1.53, 95% CI = 1.31-1.79). Furthermore, they were
      nearly twice as likely to be current smokers in adulthood compared with those
      without childhood attention problems (RR = 1.71, 95% CI = 1.38-2.11). Similar
      associations were found between components of adult executive dysfunction and
      adult smoking. DISCUSSION: Childhood cancer and treatment are associated with
      subsequent deficits in attention and EF. Early detection of these deficits will
      allow clinicians to identify patients who are at increased risk for smoking, an
      important step in promoting and maintaining health in this medically vulnerable
      population.

PMID- 20154059
TI  - China's chances, China's choices in global tobacco control.

PMID- 20154055
TI  - Preventing postpartum smoking relapse among diverse low-income women: a
      randomized clinical trial.
AB  - INTRODUCTION: Postpartum relapse rates are high among women who spontaneously
      quit smoking during pregnancy. This randomized clinical trial tested a Motivation
      and Problem-Solving (MAPS) treatment for reducing postpartum relapse among
      diverse low-income women who quit smoking during pregnancy (N = 251; 32% Black,
      30% Latino, and 36% White; 55% <$30,000/year household income). METHODS: Pregnant
      women were randomly assigned to MAPS/MAPS+ or Usual Care (UC). Continuation ratio
      logit models were used to examine differences in biochemically confirmed
      continuous abstinence at Weeks 8 and 26 postpartum by treatment group and
      moderators of the treatment effect. Analyses controlled for age, race/ethnicity,
      partner status, education, smoking rate, and the number of smokers in the
      participant's environment. RESULTS: MAPS/MAPS+ was more efficacious than UC in
      the prevention of postpartum relapse (p = .05). An interaction between treatment
      and the number of cigarettes smoked per day before quitting approached
      significance (p = .09), suggesting that the MAPS/MAPS+ treatment effect was
      stronger among women who smoked more cigarettes per day. DISCUSSION: MAPS, a
      holistic and dynamic approach to changing behavior using a combined motivational
      enhancement and social cognitive approach, is a promising intervention for
      postpartum smoking relapse prevention among low-income women, which may have
      particular relevance for women with higher prequit smoking rates.

PMID- 20154061
TI  - Electronic nicotine delivery devices: ineffective nicotine delivery and craving
      suppression after acute administration.

PMID- 20154062
TI  - Strain-dependent differences in electrogenic secretion of electrolytes across
      mouse colon epithelium.
AB  - Mice have proven to be powerful models for the study of human physiology and
      pathophysiology. With the advent of techniques for genomic manipulation, the
      possibilities for studying inherited diseases in this convenient laboratory
      mammal are increasing by the day. It has been reported that when knocking out or
      otherwise modifying genes of interest in mice, the phenotype obtained can vary
      markedly depending on the genetic background of the animals used in the study.
      The aim of this work was to study whether the genetic background can influence
      the characteristics of fluid and electrolyte transepithelial transport in the
      distal colon of three mouse strains most in use in our and other laboratories.
      Ussing chamber recordings revealed that the colons of C57Bl/6J, Sv 129 and Black
      Swiss animals have distinctive responses to the calcium agonists carbachol and
      histamine that are not explained by the presence of different types of muscarinic
      and histaminergic receptors in these tissues. We have also found differences in
      the cAMP-activated, KCNMA1-channel-dependent potassium secretion between the
      strains. We interpret this to indicate a unique distribution of KCNMA1 channels
      in lower parts of the crypt of Sv 129 colonic epithelium compared with that of
      C57Bl/6J and Black Swiss animals. The reported differences should be taken into
      account when choosing the genetic background of animals to be used for genetic
      modification.

PMID- 20154063
TI  - Benign breast disease and subsequent breast cancer: English record linkage
      studies.
AB  - BACKGROUND: Benign breast disease (BBD) increases the risk of breast cancer, but
      details of the relationship would benefit from further study in the UK. METHODS:
      Analysis of linked statistical abstracts of hospital data, including a cohort of
      20 976 women with BBD in an Oxford data set and 89 268 such women in an English
      national data set. RESULTS: Rate ratios (RRs) for breast cancer, comparing BBD
      and comparison cohorts in these two data sets, were 2.3 (95% CI: 2.2-2.5) and 3.2
      (3.0-3.3), respectively. RRs rose with increasing age at BBD diagnosis and
      remained elevated for at least 20 years after diagnosis. RRs were particularly
      high for a relatively small number of cancers occurring in the first few months
      after BBD diagnosis. CONCLUSIONS: Our findings accord well with those in other
      large studies, mostly done in the USA, in showing a sustained long-term cancer
      risk after BBD. They also demonstrate that known long-term risks of disease can
      be reliably identified from linked routine administrative hospital statistics.
      Most other studies omit cancers in the first few months after BBD. Such cases
      presumably either misdiagnosed or miscoded-merit further study to determine
      whether in fact they include diagnoses of cancer that were initially missed.

PMID- 20154064
TI  - Heat shock protein 90 inhibitors attenuate inflammatory responses in
      atherosclerosis.
AB  - AIMS: Heat shock protein 90 (HSP90) is a ubiquitous chaperone involved in the
      folding, activation, and assembly of many proteins. HSP90 inhibitors [17
      allylamino-17-demethoxygeldamycin (17-AAG)/17-dimethyl aminothylamino-17
      demethoxygeldanamycin hydrochloride (17-DMAG)] bind to and inactivate HSP90,
      increasing the heat shock response and suppressing different signalling pathways.
      We aim to investigate the effect of HSP90 inhibitors in the modulation of
      inflammatory responses during atherogenesis. METHODS AND RESULTS: In human
      atherosclerotic plaques, HSP90 immunostaining was increased in inflammatory
      regions and in plaques characterized by lower cap thickness. In cultured human
      macrophages and vascular smooth muscle cells, treatment with either 17-AAG or 17
      DMAG increased HSP70 expression and reduced transcription factor [signal
      transducers and activators of transcription (STAT) and nuclear factor-kappaB (NF
      kappaB)] activation and chemokine expression induced by proinflammatory
      cytokines. In vivo, hyperlipidaemic ApoE(-/-) mice were randomized to 17-DMAG (2
      mg/kg every 2 days, n = 11) or vehicle injected (n = 9) during 10 weeks.
      Atherosclerotic plaques of mice treated with 17-DMAG displayed increased HSP70
      expression and diminished NF-kappaB and STAT activation, along with decreased
      lesion, lipid, and macrophage content, compared with vehicle-injected mice. In
      addition, treatment with 17-DMAG significantly reduced monocyte chemoattractant
      protein-1 levels, both in plaques and in plasma. CONCLUSION: HSP90 expression is
      associated with features of plaque instability in advanced human lesions. HSP90
      inhibitors reduce inflammatory responses in atherosclerosis, suggesting that
      HSP90 could be a novel therapeutic target in atherosclerosis.

PMID- 20154065
TI  - Gadd45beta is a novel mediator of cardiomyocyte apoptosis induced by
      ischaemia/hypoxia.
AB  - AIMS: Because apoptotic death plays a critical role in cardiomyocyte loss during
      ischaemic heart injury, a detailed understanding of the mechanisms involved is
      likely to have a substantial impact on the optimization and development of
      treatment strategies. The goal of this study was to assess gene profiling during
      ischaemia/hypoxia and to evaluate the functions of ischaemia/hypoxia-responsive
      genes in in vivo and in vitro ischaemia/hypoxia-induced cardiomyocyte apoptosis
      models. METHODS AND RESULTS: DNA microarray analysis and real-time polymerase
      chain reaction were performed on hearts obtained from an in vivo rat transient
      ischaemia model and on neonatal rat cardiomyocytes from an in vitro hypoxia
      model. Three genes, namely Ddit4, Gadd45beta and Atf3, were found to be up
      regulated in vivo and in vitro. Using loss-of-function and gain-of-function
      techniques, the functions of these ischaemia/hypoxia-responsive genes were
      evaluated. Ischaemia/hypoxia-induced cardiomyocyte apoptosis was remarkably
      attenuated by the small interfering RNA-mediated down-regulation of Gadd45beta in
      vivo and in vitro, whereas ectopic Gadd45beta expression significantly aggravated
      hypoxia-induced apoptosis in vitro. CONCLUSION: These results suggest that
      Gadd45beta is a key player in ischaemia/hypoxia-induced apoptotic cardiomyocyte
      death, and that strategies based on its inhibition might be of benefit in the
      treatment of acute ischaemic heart disease.

PMID- 20154067
TI  - Association of HLA-A, -B and -DRB1 genotype with birthweight and CD34+ cell
      content: analysis of Korean newborns and their cord blood.
AB  - Birthweight and the hematopoietic progenitor cell content in cord blood affect
      and reflect fetal development, and MHC has been reported to play an important
      role in intrauterine growth. In this study, we assessed HLA-A, -B and -DRB1
      polymorphisms, birthweight and cord blood CD34(+) cell content in 1628 full-term
      healthy neonates to identify the HLA alleles that are associated with fetal
      growth in Koreans. HLA-A*31, B*47, B*51, DRB1*04 showed positive association and
      HLA-A*03, A*24, A*30, B*07, B*52, B*58, DRB1*03 showed negative association with
      birthweight and/or CD34(+) cell content; additionally, there was a greater
      association in homozygotes than heterozygotes revealed in the trend analysis of
      birthweight centile with candidate allele zygosity (A*24, P= 0.018; DRB1*04, P=
      0.047). Among these alleles, HLA-A*24 and DRB1*03 showed significant negative
      association with birthweight and/or CD34(+) cell content after Bonferroni
      correction, suggesting a significant association of these alleles with fetal
      growth in late pregnancy (A*24, P= 0.002, P(c) = 0.026; DRB1*03, P < 0.001, P(c)
      < 0.001). Various populations should be analyzed to identify different or
      consistent factors among ethnicities. Furthermore, a larger scale study that
      includes pre-terms will aid in the comprehensive understanding of these
      associations.

PMID- 20154066
TI  - Extracellular matrix, inflammation, and the angiogenic response.
AB  - Inflammation and angiogenesis are frequently coupled in pathological situations
      such as atherosclerosis, diabetes, and arthritis. The inflammatory response
      increases capillary permeability and induces endothelial activation, which, when
      persistent, results in capillary sprouting. This inflammation-induced
      angiogenesis and the subsequent remodelling steps are in large part mediated by
      extracellular matrix (ECM) proteins and proteases. The focal increase in
      capillary permeability is an early consequence of inflammation, and results in
      the deposition of a provisional fibrin matrix. Subsequently, ECM turnover by
      proteases permits an invasive program by specialized endothelial cells whose
      phenotype can be regulated by inflammatory stimuli. ECM activity also provides
      specific mechanical forces, exposes cryptic adhesion sites, and releases
      biologically active fragments (matrikines) and matrix-sequestered growth factors,
      all of which are critical for vascular morphogenesis. Further matrix remodelling
      and vascular regression contribute to the resolution of the inflammatory response
      and facilitate tissue repair.

PMID- 20154068
TI  - A potential role for keratinocyte growth factor and clarithromycin in the
      treatment of paraquat overdose.

PMID- 20154069
TI  - Gaseous emboli during off-pump surgery with T-graft technique, two different
      mechanisms.
AB  - OBJECTIVES: Gaseous embolism is a possible complication during off-pump coronary
      surgery with the use of a blower and can cause ischemic injuries. We describe two
      different possible mechanisms of carbon-dioxide embolization. METHODS: Out of
      2196 coronary bypass surgeries, between 1 January 2007 and 31 December 2009,
      there were 977 off-pump operations. Two off-pump cases (0.2%) had gaseous (carbon
      dioxide) emboli that migrated against blood stream proximally through T
      anastomoses and then into the native coronary vessels. These emboli caused a
      temporary haemodynamic deterioration in other territories. Two types of T
      anastomoses were included [saphenous vein on left internal thoracic artery (LITA)
      or right internal thoracic artery (RITA) on LITA]. RESULTS: Simple procedures and
      measurements were necessary but enough to regain haemodynamic stability. There
      was no effect on the postoperative outcome. CONCLUSION: We have concluded that
      carbon-dioxide emboli can also cause massive but temporary haemodynamic
      deterioration during off-pump surgery despite higher solubility in blood. The
      blower should be used only when a bull-dog clamp is applied on the graft. Also,
      proper de-airing and flushing of grafts is very important and avoids consequences
      of the trapped small emboli.

PMID- 20154070
TI  - Cardiac myxoma mimicking extension of renal cell carcinoma.
AB  - Cardiac myxomas are the commonest benign tumour of the heart. We are describing a
      rare presentation of a myxoma in a patient with renal cell carcinoma (RCC). Since
      there was no single reported case of myxoma with RCC, a presumptive diagnosis of
      RCC with right atrial extension of tumour thrombus was made. Both the tumours
      were resected in the same operation by radical nephrectomy with open heart
      surgery.

PMID- 20154071
TI  - Helmet continuous positive airway pressure vs oxygen therapy to improve
      oxygenation in community-acquired pneumonia: a randomized, controlled trial.
AB  - OBJECTIVE: Our objective was to evaluate the efficacy of noninvasive continuous
      positive airway pressure (CPAP) delivered by helmet in improving oxygenation in
      comparison with oxygen therapy in community-acquired pneumonia (CAP). METHODS:
      This was a multicenter, randomized, controlled trial enrolling patients with CAP
      admitted to an ED with moderate hypoxemic acute respiratory failure (ARF)
      (Pa(O(2))/Fi(O(2)) ratio > or = 210 and < or = 285). Patients were randomized to
      helmet CPAP or standard oxygen therapy (control group). The primary end point was
      the time to reach a Pa(O(2))/Fi(O(2)) ratio > 315. After reaching this value,
      patients randomized to CPAP were switched to oxygen, and the proportion of
      subjects who could maintain a Pa(O(2))/Fi(O(2)) ratio > 315 at 1 h was recorded.
      RESULTS: Forty-seven patients were recruited: 20 randomized to CPAP and 27 to
      controls. Patients randomized to CPAP reached the end point in a median of 1.5 h,
      whereas controls reached the end point in 48 h (P < .001). The proportion of
      patients who reached the primary end point was 95% (19/20) among the CPAP group
      and 30% (8/27) among controls (P < .001). One hour after reaching the primary end
      point, 2/14 patients in the CPAP group maintained a Pa(O(2))/Fi(O(2)) value >
      315. CONCLUSIONS: CPAP delivered by helmet rapidly improves oxygenation in
      patients with CAP suffering from a moderate hypoxemic ARF. This trial represents
      a proof-of-concept evaluation of the potential usefulness of CPAP in patients
      with CAP.

PMID- 20154072
TI  - Cigarette smoking as a cause of cancers other than lung cancer: an exploratory
      study using the Surveillance, Epidemiology, and End Results Program.
AB  - BACKGROUND: Cigarette smoking is causally related to several cancers,
      particularly lung cancer, yet for some cancers there are inconsistent
      associations. This study investigates the association of smoking with other
      cancers by correlating them with the regional incidence rates for lung cancer,
      which was used as a proxy for cigarette smoking. This ecologic approach relating
      cigarette smoking to cancer using a large database avoids the limitations and
      bias present in case-control and cohort studies. METHODS: Based on the assumption
      that regions with a high rate of lung cancer also have a high rate of cigarette
      smoking, our original hypothesis is that these high-intensity regions will also
      have high rates of other cancers if they are associated with cigarette smoking.
      Linear regression and correlation analysis of regional incidence rates for lung
      cancer, obtained from the Surveillance, Epidemiology, and End Results (SEER)
      Program, were plotted with incidence rates of other cancers to determine the
      association between lung cancer and the other cancers. RESULTS: Cancers that have
      a strong correlation with cigarette smoking in the literature also demonstrate a
      strong correlation with lung cancer. These cancers included urinary bladder,
      laryngeal, esophageal, colorectal, and kidney cancer. A number of cancers showed
      a weak association with cigarette smoking, such as pancreatic and liver cancer.
      Other cancers showed no correlation, such as ovarian and prostate cancer.
      CONCLUSIONS: Cancers that respectively showed a strong or absent correlation with
      lung cancer in the SEER Program were similarly strongly or weakly correlated with
      cigarette smoking in the literature. Cancers with borderline correlations show
      ambiguous results or confounding variables in the literature.

PMID- 20154073
TI  - Combined endoscopic-endobronchial ultrasound-guided fine-needle aspiration of
      mediastinal lymph nodes through a single bronchoscope in 150 patients with
      suspected lung cancer.
AB  - BACKGROUND: For mediastinal lymph nodes, biopsies must often be performed to
      accurately stage lung cancer. Endobronchial ultrasound-guided transbronchial
      needle aspiration (EBUS-TBNA) allows real-time guidance in sampling paratracheal,
      subcarinal, and hilar lymph nodes, and endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA) can sample mediastinal lymph nodes located adjacent to the
      esophagus. Nodes can be sampled and staged more completely by combining these
      procedures, but to date use of two different endoscopes has been required. We
      examined whether both procedures could be performed with a single endobronchial
      ultrasound bronchoscope. METHODS: Consecutive patients with a presumptive
      diagnosis of non-small cell lung cancer (NSCLC) underwent endoscopic staging by
      EBUS-TBNA and EUS-FNA through a single linear ultrasound bronchoscope. Surgical
      confirmation and clinical follow-up was used as the reference standard. RESULTS:
      Among 150 evaluated patients, 139 (91%; 83 men, 56 women; mean age 57.6 years)
      were diagnosed with NSCLC. In these 139 patients, 619 nodes were endoscopically
      biopsied: 229 by EUS-FNA and 390 by EBUS-TBNA. Sensitivity was 89% for EUS-FNA
      and 92% for EBUS-TBNA. The combined approach had a sensitivity of 96% and a
      negative predictive value of 95%, values higher than either approach alone. No
      complications occurred. CONCLUSIONS: The two procedures can easily be performed
      with a dedicated linear endobronchial ultrasound bronchoscope in one setting and
      by one operator. They are complementary and provide better diagnostic accuracy
      than either one alone. The combination may be able to replace more invasive
      methods as a primary staging method for patients with lung cancer.

PMID- 20154074
TI  - The effects of hypoxia on markers of coagulation and systemic inflammation in
      patients with COPD.
AB  - BACKGROUND: It has been demonstrated that there is an increased risk of venous
      thromboembolism (VTE) during air travel on flights of long duration. Patients
      with COPD are also at increased risk of VTE, particularly during exacerbations,
      possibly because of a hypercoagulable state secondary to hypoxia and/or
      heightened systemic inflammation. We investigated the effects of hypoxia on
      indices of coagulation and systemic inflammation in patients with COPD. METHODS:
      Twenty clinically stable patients with mild COPD were recruited. Patients were
      randomized to receive either medical air or 100% nitrogen through a 40% venturi
      mask at a flow rate of 10 L/min for 2 h. Blood was sampled for thrombin
      antithrombin complex (TAT), prothrombin activation fragments 1 + 2 (F(1 + 2)),
      von Willebrand factor antigen (VWF:Ag), D-dimer, and interleukin-6 (IL-6) at
      baseline and after 2 h. RESULTS: Patients in the hypoxia and control groups were
      similar in terms of age, sex, pack-years smoked, and severity of airflow
      obstruction. There was no difference in baseline TAT, F(1 + 2), VWF:Ag, D-dimer,
      or IL-6 levels between groups. In the control group, there was no change in
      markers of coagulation or systemic inflammation over the 2-h study. In patients
      who underwent hypoxic challenge, there was an increase in TAT (P < .001), F(1 +
      2) (P < .01), and IL-6 (P < .01), whereas D-dimer and VWF:Ag levels were
      unchanged. CONCLUSIONS: This study demonstrates that a 2-h hypoxic challenge in
      patients with COPD results in coagulation activation in conjunction with an
      increase in systemic inflammation.

PMID- 20154075
TI  - Resistant pathogens in nonnosocomial pneumonia and respiratory failure: is it
      time to refine the definition of health-care-associated pneumonia?
AB  - BACKGROUND: The concept of health-care-associated pneumonia (HCAP) exists to
      identify patients infected with highly resistant pathogens. It is unclear how
      precise this concept is and how well it performs as a screening tool for
      resistance. METHODS: We retrospectively identified patients presenting to the
      hospital with pneumonia complicated by respiratory failure. We examined the
      microbiology of these infections based on pneumonia type and determined the
      sensitivity and specificity of HCAP as a screen for resistance. Through logistic
      regression and modeling, we created a scoring tool for determining who may be
      infected with resistant pathogens. RESULTS: The cohort included 190 subjects (37%
      with ARDS) and we noted resistant pathogens in 33%. Resistance was more common in
      HCAP (78% vs 44%, P = .001). HCAP alone performed poorly as a screening test
      (sensitivity and specificity 78.3% and 56.2%, respectively). Variables
      independently associated with a resistant organism included immunosuppression
      (adjusted odds ratio [AOR] 4.85, P < .001), long-term care admission (AOR 2.36, P
      = .029), and prior antibiotics (AOR 2.12, P = .099). A decision rule based only
      on these factors performed moderately well at identifying resistant infections.
      The presence of HCAP itself, based on meeting defined criteria, was not
      independently associated with resistance using logistic regression to control for
      covariates. CONCLUSIONS: HCAP is common in patients presenting to the hospital
      with pneumonia leading to respiratory failure. The HCAP concept does not
      correlate well with the presence of infection due to a resistant pathogen. A
      simpler clinical decision rule based on select HCAP criteria performs as well as
      the HCAP concept for potentially guiding antibiotic decision making.

PMID- 20154076
TI  - Obstructive sleep apnea is common and independently associated with atrial
      fibrillation in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated with arrhythmias and
      cardiovascular death. Left atrial enlargement and atrial fibrillation (AF) are
      considered markers for death due to heart failure in patients with HCM.
      Obstructive sleep apnea (OSA) is independently associated with heart remodeling
      and arrhythmias in other populations. We hypothesized that OSA is common and is
      associated with heart remodeling and AF in patients with HCM. METHODS: We
      evaluated 80 consecutive stable patients with a confirmed diagnosis of HCM by
      sleep questionnaire, blood tests, echocardiography, and sleep study (overnight
      respiratory monitoring). RESULTS: OSA (apnea-hypopnea index [AHI] > 15 events/h)
      was present in 32 patients (40%). Patients with OSA were significantly older (56
      [41-64] vs 38.5 [30-53] years, P < .001) and presented higher BMI (28.2 +/- 3.5
      vs 25.2 +/- 5.2 kg/m(2), P < .01) and increased left atrial diameter (45 [42
      52.8] vs 41 [39-47] mm, P = .01) and aorta diameter (34 [30-37] vs 29 [28-32] mm,
      P < .001), compared with patients without OSA. Stepwise multiple linear
      regression showed that the AHI (P = .05) and BMI (P = .06) were associated with
      left atrial diameter. The AHI was the only variable associated with aorta
      diameter (P = .01). AF was present in 31% vs 6% of patients with and without OSA,
      respectively (P < .01). OSA (P = .03) and left atrial diameter (P = .03) were the
      only factors independently associated with AF. CONCLUSIONS: OSA is highly
      prevalent in patients with HCM and it is associated with left atrial and aortic
      enlargement. OSA is independently associated with AF, a risk factor for
      cardiovascular death in this population.

PMID- 20154077
TI  - Real prevalence of pulmonary right-to-left shunt according to genotype in
      patients with hereditary hemorrhagic telangiectasia: a transthoracic contrast
      echocardiography study.
AB  - BACKGROUND: Transthoracic contrast echocardiography (TTCE) can detect pulmonary
      right-to-left shunting (RLS) and is used to screen for pulmonary arteriovenous
      malformations (PAVMs) in patients with hereditary hemorrhagic telangiectasia
      (HHT). We studied the prevalence and size of pulmonary RLS in HHT type 1, HHT
      type 2, and HHT-negative controls, and its positive predictive value (PPV) and
      negative predictive value (NPV) for PAVMs that can be treated by embolotherapy.
      METHODS: In 343 consecutive persons referred for possible HHT as first-degree
      family members of index patients a TTCE and chest CT scan were performed. All
      persons were offered genetic analysis. RESULTS: An HHT-causing mutation was
      confirmed in 92 (mean age 41 +/- 15 y; 59% female) HHT1 relatives and in 97 (mean
      age 47 +/- 14 y; 52% female) HHT2 relatives. TTCE showed a pulmonary RLS in 78
      (85%) HHT1- and 34 (35%) HHT2-related mutation carriers, respectively (P <
      .0001). In HHT1 relatives, 29 of 53 (55%) PAVMs and in HHT2 relatives three of 17
      (18%) PAVMS were treated, resulting in a PPV of TTCE for treatable PAVMs of 36.3%
      and 8.3%, respectively. The accompanying NPV was 100%. A minimal, moderate, or
      large shunt was present in 12 (13%), 24 (26%), and 42 (46%) HHT1-related, and in
      20 (21%), 6 (6%), and 8 (8%) HHT2-related mutation carriers, respectively (P for
      trend < .0001). A large shunt predicted treatable PAVMs in 55.8% of HHT1
      relatives and 37.5% of HHT2 relatives. TTCE was positive in four (6%) of 63
      persons without HHT. CONCLUSIONS: A pulmonary shunt on TTCE is more prevalent and
      larger in HHT1- compared with HHT2-related mutation carriers. Shunt grading is
      helpful to predict treatable PAVMs, particularly in the HHT2 group. TTCE is also
      positive in a small fraction of persons without HHT.

PMID- 20154078
TI  - A comparison of obese and nonobese people with asthma: exploring an asthma
      obesity interaction.
AB  - OBJECTIVE: The objectives of our study were to compare patient characteristics
      and severity of disease in obese and normal-weight-confirmed people with asthma
      and to explore reasons for misdiagnosis of asthma, including potential
      interactions with obesity. METHODS: We randomly selected patients with physician
      diagnosed asthma from eight Canadian cities. Asthma diagnosis was confirmed via a
      sequential lung function testing algorithm. Logistic analysis was conducted to
      compare obese and normal-weight-confirmed people with asthma and to assess
      characteristics associated with misdiagnosis of asthma. Interaction with obesity
      was investigated. RESULTS: Complete assessments were obtained on 496 subjects who
      reported physician-diagnosed asthma (242 obese and 254 normal-weight subjects);
      346 had asthma confirmed with sequential lung testing, and in 150 subjects a
      diagnosis of asthma was ruled out. Obese subjects with asthma were significantly
      more likely to be men, have a history of hypertension and gastroesophageal reflux
      disease, and have a lower FEV(1) compared with normal-weight subjects with
      asthma. Older subjects, men, and subjects with higher FEV(1) were more likely to
      have received misdiagnoses of asthma. Obesity was not an independent predictor of
      misdiagnosis, however there was an interaction between obesity and urgent visits
      for respiratory symptoms. The odds ratio for receiving a misdiagnosis of asthma
      for obese individuals as compared with normal-weight individuals was 4.08 (95%
      CI, 1.23-13.5) for those with urgent visits in the past 12 months. CONCLUSIONS:
      Obese people with asthma have lower lung function and more comorbidities compared
      with normal-weight people with asthma. Obese individuals who make urgent visits
      for respiratory symptoms are more likely to receive a misdiagnosis of asthma.

PMID- 20154079
TI  - Medical thoracoscopy vs CT scan-guided Abrams pleural needle biopsy for diagnosis
      of patients with pleural effusions: a randomized, controlled trial.
AB  - BACKGROUND: In cases of pleural effusion, tissue samples can be obtained through
      Abrams needle pleural biopsy (ANPB), thoracoscopy, or cutting-needle pleural
      biopsy under the guidance of CT scan (CT-CNPB) for histopathologic analysis. This
      study aimed to compare the diagnostic efficiency and reliability of ANPB under CT
      scan guidance (CT-ANPB) with that of medical thoracoscopy in patients with
      pleural effusion. METHODS: Between January 2006 and January 2008, 124 patients
      with exudative pleural effusion that could not be diagnosed by cytologic analysis
      were included in the study. All patients were randomized after the CT scan was
      performed. Patients either underwent CT-ANPB or thoracoscopy. The two groups were
      compared in terms of diagnostic sensitivity and complications associated with the
      methods used. RESULTS: Of the 124 patients, malignant mesothelioma was diagnosed
      in 33, metastatic pleural disease in 47, benign pleural disease in 42, and two
      were of indeterminate origin. In the CT-ANPB group, the diagnostic sensitivity
      was 87.5%, as compared with 94.1% in the thoracoscopy group; the difference was
      not statistically significant (P = .252). No difference was identified between
      the sensitivities of the two methods based on the cause, the CT scan findings,
      and the degree of pleural thickening. Complication rates were low and acceptable.
      CONCLUSION: We recommend the use of CT-ANPB as the primary method of diagnosis in
      patients with pleural thickening or lesions observed by CT scan. In patients with
      only pleural fluid appearance on CT scan and in those who may have benign pleural
      pathologies other than TB, the primary method of diagnosis should be medical
      thoracoscopy. TRIAL REGISTRATION: clinicaltrials.gov; Identifier: NCT00720954.

PMID- 20154080
TI  - Small- and moderate-size right-to-left shunts identified by saline contrast
      echocardiography are normal and unrelated to migraine headache.
AB  - BACKGROUND: We suspected, based on clinical experience, that the prevalence of
      both intracardiac and pulmonary arteriovenous malformations (PAVMs) is higher
      than previously reported in a healthy population when using modern ultrasound
      technology combined with a rigorous saline contrast echocardiogram (SCE)
      protocol. We hypothesized the prevalence of right-to-left shunts (RLSs) would be
      so high when using this sensitive technique that there would be no significant
      association of RLS with migraine headache. METHODS: We recruited 104 healthy
      volunteers to undergo an SCE followed by completion of a migraine questionnaire.
      The SCEs were meticulously graded for shunt size and location based on left-sided
      heart contrast quantity and timing. The migraine headache questionnaire was
      graded by a neurologist blinded to SCE results. RESULTS: One hundred four
      subjects underwent the study protocol. We found 71% of subjects exhibited
      evidence of RLS. Patent foramen ovale (PFO) was identified in 40 (38%), PAVM was
      identified in 29 (28%), and five subjects had evidence of both (5%). Based on
      questionnaires, 42 (40%) of the subjects had migraine headache (29% with aura).
      There was no significant association of migraine headache with PFO (OR, 0.59; 95%
      CI, 0.16-2.12; P = .54) or PAVM (OR, 0.8; 95% CI, 0.34-1.9; P = .67), although
      only 13 (13%) of the subjects had evidence of large RLS. CONCLUSIONS: When using
      modern ultrasound technology combined with a rigorous SCE technique, the majority
      of healthy subjects demonstrate some degree of RLS. PAVM in an otherwise healthy
      population is common. Small- and moderate-size RLSs do not appear to be
      significantly associated with migraine headache.

PMID- 20154081
TI  - Immunosuppressive cyclosporin A activates AKT in keratinocytes through PTEN
      suppression: implications in skin carcinogenesis.
AB  - Non-melanoma skin cancer, the most common neoplasia after solid organ
      transplantation, causes serious morbidity and mortality and is related to sun
      exposure. Cyclosporin A (CsA) has been used widely to prevent rejection in organ
      transplantation. The mechanism of CsA action in causing cancer was thought to be
      well understood via immunosuppression. Here, we show that CsA promotes primary
      skin tumor growth in immune-deficient mice and keratinocyte growth in vitro. In
      addition, CsA enhances keratinocyte survival from removal of extracellular matrix
      or UVB radiation. At the molecular level, CsA increases AKT activation after
      serum treatment and UVB irradiation. Furthermore we found that expression of
      PTEN, the negative regulator of AKT activation, is significantly reduced post-CsA
      in human HaCaT and A431 cells and in mouse skin in vivo. CsA-induced PTEN down
      regulation occurs at the transcription level and is epidermal growth factor
      receptor-dependent. Such PTEN suppression is required for increased AKT
      activation. Inhibition of AKT activation abolishes CsA-promoted growth and
      survival, indicating that AKT hyperactivation is essential for both growth and
      survival of CsA-treated cells. In addition, mTOR signaling as a known AKT
      downstream pathway is required for CsA-enhanced growth and survival. Taken
      together, we have identified the PTEN/AKT pathway as new molecular targets of CsA
      in epidermal keratinocytes, suggesting a previously unknown mechanism in CsA
      enhanced skin carcinogenesis. Our findings challenge assumptions about how CsA
      associated tumors arise in skin.

PMID- 20154082
TI  - Heparan sulfate chain valency controls syndecan-4 function in cell adhesion.
AB  - Fibroblasts null for the transmembrane proteoglycan, syndecan-4, have an altered
      actin cytoskeleton, compared with matching wild-type cells. They do not organize
      alpha-smooth muscle actin into bundles, but will do so when full-length syndecan
      4 is re-expressed. This requires the central V region of the core protein
      cytoplasmic domain, though not interactions with PDZ proteins. A second key
      requirement is multiple heparan sulfate chains. Mutant syndecan-4 with no chains,
      or only one chain, failed to restore the wild-type phenotype, whereas those
      expressing two or three were competent. However, clustering of one-chain syndecan
      4 forms with antibodies overcame the block, indicating that valency of
      interactions with ligands is a key component of syndecan-4 function. Measurements
      of focal contact/adhesion size and focal adhesion kinase phosphorylation
      correlated with syndecan-4 status and alpha-smooth muscle actin organization,
      being reduced where syndecan-4 function was compromised by a lack of multiple
      heparan sulfate chains.

PMID- 20154083
TI  - High temperature requirement A3 (HtrA3) promotes etoposide- and cisplatin-induced
      cytotoxicity in lung cancer cell lines.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Here we show
      for the first time that HtrA3 is a mitochondrial stress-response factor that
      promotes cytotoxicity to etoposide and cisplatin in lung cancer cell lines.
      Exogenous expression of wild type HtrA3 domain variants significantly attenuated
      cell survival with etoposide and cisplatin treatment in lung cancer cell lines
      H157 and A549 compared with expression of protease inactive mutants (S305A) or
      vector control. Conversely, HtrA3 suppression promoted cell survival with
      etoposide and cisplatin treatment in lung cancer cell lines Hop62 and HCC827.
      Survival was attenuated by re-expression of wild type HtrA3 variants during
      treatment but not by protease inactive mutants or vector control. HtrA3 also co
      fractionated and co-localized with mitochondrial markers with both endogenous and
      exogenous expression in normal lung and lung cancer cell lines but was
      translocated from mitochondria following etoposide treatment. Moreover, HtrA3
      translocation from mitochondria correlated with an increase in cell death that
      was attenuated by either HtrA3 suppression or Bcl-2 overexpression. Taken
      together, these results suggest that HtrA3 may be a previously uncharacterized
      mitochondrial cell death effector whose serine protease function may be crucial
      to modulating etoposide- and cisplatin-induced cytotoxicity in lung cancer cell
      lines.

PMID- 20154084
TI  - Roles of the lipid-binding motifs of Atg18 and Atg21 in the cytoplasm to vacuole
      targeting pathway and autophagy.
AB  - Atg18 and Atg21 are homologous WD-40 repeat proteins that bind phosphoinositides
      via a novel conserved Phe-Arg-Arg-Gly motif and function in autophagy-related
      pathways. Atg18 is required for the cytoplasm to vacuole targeting (Cvt) pathway
      and autophagy, whereas Atg21 is only required for the Cvt pathway. Currently, the
      functions of both proteins are poorly understood. Here, we examined the
      relationship between the phosphatidylinositol 3-phosphate (PtdIns(3)P)-binding
      abilities of Atg18 and Atg21 and autophagy by expressing variants of these
      proteins that have mutations in their phosphoinositide-binding motifs. Cells
      expressing PtdIns(3)P-binding mutants of both these proteins showed highly
      reduced autophagy. Furthermore, the localization of components of two related
      ubiquitin-like protein conjugation systems, Atg8 and Atg16, to the phagophore
      assembly site is affected. Consistent with the aberrant localization of the above
      Atg proteins, precursor Ape1, a cargo of the Cvt pathway and autophagy, is
      partially protease-sensitive in starvation conditions. This finding suggests a
      requirement for the PtdIns(3)P binding capability of Atg18 and Atg21 in efficient
      completion of the sequestering autophagic vesicles. Finally, using a multiple
      knock-out strain, we found that Atg18 and Atg21 facilitate the recruitment of
      Atg8-PE to the site of autophagosome formation and protect it from premature
      cleavage by Atg4, which represents a key aspect of post-translational autophagy
      regulation. Taken together, our results suggest that PtdIns(3)P binding by at
      least Atg18 or Atg21 is required for robust autophagic activity and that the
      PtdIns(3)P-binding motifs of Atg18 and Atg21 can compensate for one another in
      the recruitment of Atg components that are dependent on PtdIns(3)P for their
      phagophore assembly site association.

PMID- 20154085
TI  - Self-assembly of severe acute respiratory syndrome coronavirus membrane protein.
AB  - Coronavirus membrane (M) protein can form virus-like particles (VLPs) when
      coexpressed with nucleocapsid (N) or envelope (E) proteins, suggesting a pivotal
      role for M in virion assembly. Here we demonstrate the self-assembly and release
      of severe acute respiratory syndrome coronavirus (SARS-CoV) M protein in medium
      in the form of membrane-enveloped vesicles with densities lower than those of
      VLPs formed by M plus N. Although efficient N-N interactions require the presence
      of RNA, we found that M-M interactions were RNA-independent. SARS-CoV M was
      observed in both the Golgi area and plasma membranes of a variety of cells.
      Blocking M glycosylation does not appear to significantly affect M plasma
      membrane labeling intensity, M-containing vesicle release, or VLP formation.
      Results from a genetic analysis indicate involvement of the third transmembrane
      domain of M in plasma membrane-targeting signal. Fusion proteins containing M
      amino-terminal 50 residues encompassing the first transmembrane domain were found
      to be sufficient for membrane binding, multimerization, and Golgi retention.
      Surprisingly, we found that fusion proteins lacking all three transmembrane
      domains were still capable of membrane binding, Golgi retention, and interacting
      with M. The data suggest that multiple SARS-CoV M regions are involved in M self
      assembly and subcellular localization.

PMID- 20154086
TI  - Activation and stiffness of the inhibited states of F1-ATPase probed by single
      molecule manipulation.
AB  - F(1)-ATPase (F(1)), a soluble portion of F(o)F(1)-ATP synthase (F(o)F(1)), is an
      ATP-driven motor in which gammaepsilon subunits rotate in the alpha(3)beta(3)
      cylinder. Activity of F(1) and F(o)F(1) from Bacillus PS3 is attenuated by the
      epsilon subunit in an inhibitory extended form. In this study we observed ATP
      dependent transition of epsilon in single F(1) molecules from extended form to
      hairpin form by fluorescence resonance energy transfer. The results justify the
      previous bulk experiments and ensure that fraction of F(1) with hairpin epsilon
      directly determines the fraction of active F(1) at any ATP concentration. Next,
      mechanical activation and stiffness of epsilon-inhibited F(1) were examined by
      the forced rotation of magnetic beads attached to gamma. Compared with ADP
      inhibition, which is another manner of inhibition, rotation by a larger angle was
      required for the activation from epsilon inhibition when the beads were forced to
      rotate to ATP hydrolysis direction, and more torque was required to reach the
      same rotation angle when beads were forced to rotate to ATP synthesis direction.
      The results imply that if F(o)F(1) is resting in the epsilon-inhibited state,
      F(o) motor must transmit to gamma a torque larger than expected from
      thermodynamic equilibrium to initiate ATP synthesis.

PMID- 20154087
TI  - Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down
      regulation of cell survival proteins and up-regulation of death receptors.
AB  - Whether celastrol, a triterpene from traditional Chinese medicine, can modulate
      the anticancer effects of TRAIL, the cytokine that is currently in clinical
      trial, was investigated. As indicated by assays that measure plasma membrane
      integrity, phosphatidylserine exposure, mitochondrial activity, and activation of
      caspase-8, caspase-9, and caspase-3, celastrol potentiated the TRAIL-induced
      apoptosis in human breast cancer cells, and converted TRAIL-resistant cells to
      TRAIL-sensitive cells. When examined for its mechanism, we found that the
      triterpene down-regulated the expression of cell survival proteins including
      cFLIP, IAP-1, Bcl-2, Bcl-xL, survivin, and XIAP and up-regulated Bax expression.
      In addition, we found that celastrol induced the cell surface expression of both
      the TRAIL receptors DR4 and DR5. This increase in receptors was noted in a wide
      variety of cancer cells including breast, lung, colorectal, prostate, esophageal,
      and pancreatic cancer cells, and myeloid and leukemia cells. Gene silencing of
      the death receptor abolished the effect of celastrol on TRAIL-induced apoptosis.
      Induction of the death receptor by the triterpenoid was found to be p53
      independent but required the induction of CAAT/enhancer-binding protein
      homologous protein (CHOP), inasmuch as gene silencing of CHOP abolished the
      induction of DR5 expression by celastrol and associated enhancement of TRAIL
      induced apoptosis. We found that celastrol also induced reactive oxygen species
      (ROS) generation, and ROS sequestration inhibited celastrol-induced expression of
      CHOP and DR5, and consequent sensitization to TRAIL. Overall, our results
      demonstrate that celastrol can potentiate the apoptotic effects of TRAIL through
      down-regulation of cell survival proteins and up-regulation of death receptors
      via the ROS-mediated up-regulation of CHOP pathway.

PMID- 20154088
TI  - Distinct role of Kruppel-like factor 11 in the regulation of prostaglandin E2
      biosynthesis.
AB  - Kruppel-like factor (KLF) proteins are emerging as key regulators of lipid
      metabolism, diabetes, and the biosynthesis of immunological cytokines. However,
      their role in the synthesis of prostaglandins, widely known biochemical mediators
      that act in a myriad of cell biological processes remain poorly understood.
      Consequently, in this study a comprehensive investigation at the cellular,
      biochemical, and molecular levels reveal that KLF11 inhibits prostaglandin E(2)
      synthesis via transcriptional silencing of the promoter of its biosynthetic
      enzyme, cytosolic phospholipase A2alpha. Mechanistically, KLF11 accomplishes this
      function by binding to the promoter via specific GC-rich sites and recruiting the
      Sin3-histone deacetylase chromatin remodeling complex. Further functional
      characterization reveals that this function of KLF11 can be reversed by epidermal
      growth factor receptor-AKT-mediated post-translational modification of threonine
      56, a residue within its Sin3-binding domain. This is the first evidence
      supporting a relevant role for any KLF protein in doing both: transcriptionally
      inhibiting prostaglandin biosynthesis and its reversibility by an epidermal
      growth factor receptor-AKT signaling-mediated posttranslational mechanisms.

PMID- 20154089
TI  - Endogenous proteolytic cleavage of disease-associated prion protein to produce C2
      fragments is strongly cell- and tissue-dependent.
AB  - The abnormally folded form of the prion protein (PrP(Sc)) accumulating in nervous
      and lymphoid tissues of prion-infected individuals can be naturally cleaved to
      generate a N-terminal-truncated fragment called C2. Information about the
      identity of the cellular proteases involved in this process and its possible role
      in prion biology has remained limited and controversial. We investigated PrP(Sc)
      N-terminal trimming in different cell lines and primary cultured nerve cells, and
      in the brain and spleen tissue from transgenic mice infected by ovine and mouse
      prions. We found the following: (i) the full-length to C2 ratio varies
      considerably depending on the infected cell or tissue. Thus, in primary neurons
      and brain tissue, PrP(Sc) accumulated predominantly as untrimmed species, whereas
      efficient trimming occurred in Rov and MovS cells, and in spleen tissue. (ii)
      Although C2 is generally considered to be the counterpart of the PrP(Sc)
      proteinase K-resistant core, the N termini of the fragments cleaved in vivo and
      in vitro can actually differ, as evidenced by a different reactivity toward the
      Pc248 anti-octarepeat antibody. (iii) In lysosome-impaired cells, the ratio of
      full-length versus C2 species dramatically increased, yet efficient prion
      propagation could occur. Moreover, cathepsin but not calpain inhibitors markedly
      inhibited C2 formation, and in vitro cleavage by cathepsins B and L produced
      PrP(Sc) fragments lacking the Pc248 epitope, strongly arguing for the primary
      involvement of acidic hydrolases of the endolysosomal compartment. These findings
      have implications on the molecular analysis of PrP(Sc) and cell pathogenesis of
      prion infection.

PMID- 20154090
TI  - Ubiquilin modifies TDP-43 toxicity in a Drosophila model of amyotrophic lateral
      sclerosis (ALS).
AB  - TDP-43 (43-kDa TAR DNA-binding protein) is a major constituent of ubiquitin
      positive cytosolic aggregates present in neurons of patients with amyotrophic
      lateral sclerosis (ALS) and ubiquitin-positive fronto-temporal lobar degeneration
      (FTLD-U). Inherited mutations in TDP-43 have been linked to familial forms of
      ALS, indicating a key role for TDP-43 in disease pathogenesis. Here, we describe
      a Drosophila melanogaster model of TDP-43 proteinopathy. Expression of wild-type
      human TDP-43 protein in Drosophila motor neurons led to motor dysfunction and
      dramatic reduction of life span. Interestingly, coexpression of ubiquilin 1, a
      previously identified TDP-43-interacting protein with suspected functions in
      autophagy and proteasome targeting, reduced steady-state TDP-43 expression but
      enhanced the severity of TDP-43 phenotypes. Finally, ectopically expressed TDP-43
      was largely localized to motor neuron nuclei, suggesting that expression of wild
      type TDP-43 alone is detrimental even in the absence of cytosolic aggregation.
      Our findings demonstrate that TDP-43 exerts cell-autonomous neurotoxicity in
      Drosophila and further imply that dose-dependent alterations of TDP-43 nuclear
      function may underlie motor neuron death in ALS.

PMID- 20154091
TI  - The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with
      the clathrin machinery.
AB  - Rabs constitute the largest family of monomeric GTPases, yet for the majority of
      Rabs relatively little is known about their activation and recruitment to vesicle
      trafficking pathways. We recently identified connecdenn (DENND1A), which contains
      an N-terminal DENN (differentially expressed in neoplastic versus normal cells)
      domain, a common and evolutionarily ancient protein module. Through its DENN
      domain, connecdenn functions enzymatically as a guanine-nucleotide exchange
      factor (GEF) for Rab35. Here we identify two additional connecdenn family members
      and demonstrate that all connecdenns function as Rab35 GEFs, albeit with
      different levels of activity. The DENN domain of connecdenn 1 and 2 binds Rab35,
      whereas connecdenn 3 does not, indicating that Rab35 binding and activation are
      separable functions. Through their highly divergent C termini, each of the
      connecdenns binds to clathrin and to the clathrin adaptor AP-2. Interestingly,
      all three connecdenns use different mechanisms to bind AP-2. Characterization of
      connecdenn 2 reveals binding to the beta2-ear of AP-2 on a site that overlaps
      with that used by the autosomal recessive hypercholesterolemia protein and
      betaarrestin, although the sequence used by connecdenn 2 is unique. Loss of
      connecdenn 2 function through small interference RNA knockdown results in an
      enlargement of early endosomes, similar to what is observed upon loss of Rab35
      activity. Our studies reveal connecdenn DENN domains as generalized GEFs for
      Rab35 and identify a new AP-2-binding motif, demonstrating a complex link between
      the clathrin machinery and Rab35 activation.

PMID- 20154092
TI  - Real-time structural transitions are coupled to chemical steps in ATP hydrolysis
      by Eg5 kinesin.
AB  - At the biochemical level, motor proteins are enzymatic molecules that function by
      converting chemical energy into mechanical motion. The key element for energy
      transduction and a major unresolved question common for all motor proteins is the
      coordination between the chemical and conformational steps in ATP hydrolysis.
      Here we show time-lapse monitoring of an in vitro ATP hydrolysis reaction by the
      motor domain of a human Kinesin-5 protein (Eg5) using difference Fourier
      transform infrared spectroscopy and UV photolysis of caged ATP. In this first
      continuous observation of a biological reaction coordinate from substrate to
      product, direct spectral markers for two catalytic events are measured: proton
      abstraction from nucleophilic water by the catalytic base and formation of the
      inorganic phosphate leaving group. Simultaneous examination of conformational
      switching in Eg5, in parallel with catalytic steps, shows structural transitions
      in solution consistent with published crystal structures of the prehydrolytic and
      ADP-bound states. In addition, we detect structural modifications in the Eg5
      motor domain during bond cleavage between the beta- and gamma-phosphates of ATP.
      This conclusion challenges mechanochemical models for motor proteins that utilize
      only two stages of the catalytic cycle to drive force and motion.

PMID- 20154094
TI  - Does a home-based strength and balance programme in people aged > or =80 years
      provide the best value for money to prevent falls? A systematic review of
      economic evaluations of falls prevention interventions.
AB  - OBJECTIVES: To investigate the value for money of strategies to prevent falls in
      older adults living in the community. DESIGN: Systematic review of peer reviewed
      journal articles reporting an economic evaluation of a falls prevention
      intervention as part of a randomised controlled trial or a controlled trial, or
      using an analytical model. MEDLINE, PUBMED, EMBASE and NHS EED databases were
      searched to identify cost-effectiveness, cost-utility and cost-benefit studies
      from 1945 through July 2008. MAIN OUTCOME MEASURES: The primary outcome measure
      was incremental cost-effectiveness, cost-utility and cost-benefit ratios in the
      reported currency and in pounds sterling at 2008 prices. The quality of the
      studies was assessed using two instruments: (1) an economic evaluation checklist
      developed by Drummond and colleagues and (2) the Quality of Health Economic
      Studies instrument. RESULTS: Nine studies meeting our inclusion criteria included
      eight cost-effectiveness analyses, one cost-utility and one cost-benefit
      analysis. Three effective falls prevention strategies were cost saving in a
      subgroup of PARTICIPANTS: (1) an individually customised multifactorial programme
      in those with four or more of the eight targeted fall risk factors, (2) the home
      based Otago Exercise Programme in people > or =80 years and (3) a home safety
      programme in the subgroup with a previous fall. These three findings were from
      six studies that scored > or =75% on the Quality of Health Economic Studies
      instrument. CONCLUSIONS: Best value for money came from effective single factor
      interventions such as the Otago Exercise Programme which was cost saving in
      adults 80 years and older. This programme has broad applicability thus warranting
      warrants health policy decision-makers' close scrutiny.

PMID- 20154095
TI  - Irritable walls: the plant extracellular matrix and signaling.

PMID- 20154096
TI  - Metabolome and photochemical analysis of rice plants overexpressing Arabidopsis
      NAD kinase gene.
AB  - The chloroplastic NAD kinase (NADK2) is reported to stimulate carbon and nitrogen
      assimilation in Arabidopsis (Arabidopsis thaliana), which is vulnerable to high
      light. Since rice (Oryza sativa) is a monocotyledonous plant that can adapt to
      high light, we studied the effects of NADK2 expression in rice by developing
      transgenic rice plants that constitutively expressed the Arabidopsis
      chloroplastic NADK gene (NK2 lines). NK2 lines showed enhanced activity of NADK
      and accumulation of the NADP(H) pool, while intermediates of NAD derivatives were
      unchanged. Comprehensive analysis of the primary metabolites in leaves using
      capillary electrophoresis mass spectrometry revealed elevated levels of amino
      acids and several sugar phosphates including ribose-1,5-bisphosphate, but no
      significant change in the levels of the other metabolites. Studies of chlorophyll
      fluorescence and gas change analyses demonstrated greater electron transport and
      CO2 assimilation rates in NK2 lines, compared to those in the control. Analysis
      of oxidative stress response indicated enhanced tolerance to oxidative stress in
      these transformants. The results suggest that NADP content plays a critical role
      in determining the photosynthetic electron transport rate in rice and that its
      enhancement leads to stimulation of photosynthesis metabolism and tolerance of
      oxidative damages.

PMID- 20154097
TI  - Multiple roles and interaction factors of an E-box element in Chlamydomonas
      reinhardtii.
AB  - The two subunits of the circadian RNA-binding protein CHLAMY1 from Chlamydomonas
      reinhardtii are involved in maintaining period (C1 subunit) and phase (C3
      subunit) of the circadian clock. C1 coregulates the level of C3. Overexpression
      of C1 causes a parallel increase in C3. Both subunits can also integrate
      temperature information, resulting in hyperphosphorylation of C1 and up
      regulation of C3 at low temperature. Temperature-dependent up-regulation of C3 is
      mediated predominantly by an E-box element and only partially by two DREB1A-boxes
      that are situated within the C3 promoter. The E-box element is also involved in
      circadian C3 expression. Here, we show that the C3 promoter region drives C3
      coregulation by C1. We also found that replacement of the E-box prevents the
      coregulation of C3 in strains overexpressing C1. In contrast, replacement of any
      of the two DREB1A-boxes does not influence either the coregulation of C3 by
      increased levels of C1 or circadian C3 expression. Thus, the E-box has multiple
      key roles, including temperature-dependent up-regulation of C3, its circadian
      expression, and its coregulation by C1. Using mobility shift assays and DNA
      affinity chromatography along with mass spectrometry, we characterized proteins
      binding specifically to the E-box region and identified five of them. By
      immunoblotting, we could further show that C3 that was detected in nuclear
      extracts can be found in the E-box-binding protein complex. Our data indicate a
      complex transcriptional mechanism of C3 up-regulation and a positive feedback of
      C3 on its own promoter region.

PMID- 20154098
TI  - Phytochrome regulation of branching in Arabidopsis.
AB  - The red light:far-red light ratio perceived by phytochromes controls plastic
      traits of plant architecture, including branching. Despite the significance of
      branching for plant fitness and productivity, there is little quantitative and
      mechanistic information concerning phytochrome control of branching responses in
      Arabidopsis (Arabidopsis thaliana). Here, we show that in Arabidopsis, the
      negative effects of the phytochrome B mutation and of low red light:far-red light
      ratio on branching were largely due to reduced bud outgrowth capacity and an
      increased degree of correlative inhibition acting on the buds rather than due to
      a reduced number of leaves and buds available for branching. Phytochrome effects
      on the degree of correlative inhibition required functional BRANCHED1 (BRC1),
      BRC2, AXR1, MORE AXILLARY GROWTH2 (MAX2), and MAX4. The analysis of gene
      expression in selected buds indicated that BRC1 and BRC2 are part of different
      gene networks. The BRC1 network is linked to the growth capacity of specific
      buds, while the BRC2 network is associated with coordination of growth among
      branches. We conclude that the branching integrators BRC1 and BRC2 are necessary
      for responses to phytochrome, but they contribute differentially to these
      responses, likely acting through divergent pathways.

PMID- 20154099
TI  - The catalytic and protein-protein interaction domains are required for APM1
      function.
AB  - Aminopeptidase M1 (APM1) is essential for embryonic, vegetative, and reproductive
      development in Arabidopsis (Arabidopsis thaliana). Here, we show that, like
      mammalian M1 proteases, APM1 appears to have distinct enzymatic and protein
      protein interaction domains and functions as a homodimer. Arabidopsis seedlings
      treated with ezetimibe, an inhibitor of M1 protein-protein interactions, mimicked
      a subset of apm1 phenotypes distinct from those resulting from treatment with PAQ
      22, an inhibitor of M1 catalytic activity, suggesting that the APM1 catalytic and
      interaction domains can function independently. apm1-1 knockdown mutants
      transformed with catalytically inactive APM1 did not prevent seedling lethality.
      However, apm1-2 has a functional enzymatic domain but lacks the carboxyl (C)
      terminus, and transformation with catalytically inactive APM1 rescued the mutant.
      Overexpression of human insulin-responsive aminopeptidase/oxytocinase rescued all
      apm1 phenotypes, suggesting that the catalytic activity was sufficient to
      compensate for loss of APM1 function, while overexpression of catalytically
      inactive insulin-responsive aminopeptidase/oxytocinase only rescued apm1-2.
      Increased catalytic activity alone is not sufficient to compensate for loss of
      APM1 function, as overexpression of another Arabidopsis M1 family member lacking
      an extended C terminus did not rescue apm1-1. The protein interactions
      facilitating enzymatic activity appear to be dependent on the C terminus of APM1,
      as transformation with an open reading frame containing an internal deletion of a
      portion of the C terminus or a point mutation in a dileucine motif did not rescue
      the mutant. These results suggest that both the catalytic and interaction domains
      are necessary for APM1 function but that APM1 function and dimerization do not
      require these domains to be present in the same linear molecule.

PMID- 20154100
TI  - Annexins: components of the calcium and reactive oxygen signaling network.

PMID- 20154101
TI  - Antidiabetic effect of some medicinal plants of Oriental Morocco in neonatal non
      insulin-dependent diabetes mellitus rats.
AB  - The goal of the present study is to test the effect of water extract (WE) of four
      medicinal plants used as antidiabetics in Eastern Morocco (Arbutus unedo: Au,
      Ammoides pusilla: Ap, Thymelaea hirsuta: Th, and Urtica dioica: Ud). These plants
      are used in cooking to bring out the flavor in a dish or to complement it. The
      first experiment was realized in order to determine the antidiabetic effect of
      the WE of these plants during 5 weeks' treatment. Seven groups of Wistar rats
      were used: Healthy controls, neonatal streptozotocin (n-stz) induced-diabetic
      rats (90 mg/kg; intraperitoneally [i.p.]), n-stz + tolbutamide (400 mg/l), and 4
      groups n-stz + WE of plants (400 mg/l, drink water). The percentages of Plasma
      glucose lowering effect were, respectively for Au, Ap, Th, Ud and tolbutamide:
      31.6 % p<0.01, 27.4 % p<0.05, 38.2 % p<0.01, 13 % and 33.9 % p<0.05 when compared
      with untreated diabetic controls. In a second experiment, oral glucose tolerance
      tests were carried out in n-stz induced-diabetic rats. The i.p. administration of
      the water extract (WE) of Ap and Ud (150 mg/kg) 30 minutes before the glucose
      overload (2 g/kg) showed a significant reduction glycemia, respectively of 36 %
      at 60 min (p<0.05) and 50 % at 180 min (p<0.05) after glucose overload compared
      with controls. In contrast, the effect of WE of Au and Th (150 mg/kg, i.p.) was
      not significant. The in vitro study of glucose utilization by isolated rat
      hemidiaphragm suggests that these extracts in combination with insulin potentiate
      its activity and enhance the utilization of glucose. In conclusion, it seems that
      these plants possess antidiabetic activity.

PMID- 20154102
TI  - Granisetron ameliorates acetic acid-induced colitis in rats.
AB  - Inflammatory bowel disease (IBD) is a chronically relapsing inflammation of the
      gastrointestinal tract, of which the definite etiology remains ambiguous.
      Considering the adverse effects and incomplete efficacy of currently administered
      drugs, it is indispensable to explore new candidates with more desirable
      therapeutic profiles. 5-HT( 3) receptor antagonists have shown analgesic and anti
      inflammatory properties in vitro and in vivo. This study aims to investigate
      granisetron, a 5-HT( 3) receptor antagonist, in acetic acid-induced rat colitis
      and probable involvement of 5-HT(3) receptors. Colitis was rendered by
      instillation of 1 mL of 4% acetic acid (vol/vol) and after 1 hour, granisetron (2
      mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, 5 mg/kg), a 5
      HT( 3) receptor agonist, or granisetron + mCPBG was given intraperitoneally.
      Twenty-four hours following colitis induction, animals were sacrificed and distal
      colons were assessed macroscopically, histologically and biochemically
      (malondialdehyde, myeloperoxidase, tumor necrosis factor-alpha, interleukin-1
      beta and interleukin-6). Granisetron or dexamethasone significantly (p < .05)
      improved macroscopic and histologic scores, curtailed myeloperoxidase activity
      and diminished colonic levels of inflammatory cytokines and malondialdehyde. The
      protective effects of granisetron were reversed by concurrent administration of
      mCPBG. Our data suggests that the salutary effects of granisetron in acetic acid
      colitis could be mediated by 5-HT(3) receptors.

PMID- 20154103
TI  - Requirements for construction of a functional hybrid complex of photosystem I and
      [NiFe]-hydrogenase.
AB  - The development of cellular systems in which the enzyme hydrogenase is
      efficiently coupled to the oxygenic photosynthesis apparatus represents an
      attractive avenue to produce H(2) sustainably from light and water. Here we
      describe the molecular design of the individual components required for the
      direct coupling of the O(2)-tolerant membrane-bound hydrogenase (MBH) from
      Ralstonia eutropha H16 to the acceptor site of photosystem I (PS I) from
      Synechocystis sp. PCC 6803. By genetic engineering, the peripheral subunit PsaE
      of PS I was fused to the MBH, and the resulting hybrid protein was purified from
      R. eutropha to apparent homogeneity via two independent affinity
      chromatographical steps. The catalytically active MBH-PsaE (MBH(PsaE)) hybrid
      protein could be isolated only from the cytoplasmic fraction. This was
      surprising, since the MBH is a substrate of the twin-arginine translocation
      system and was expected to reside in the periplasm. We conclude that the
      attachment of the additional PsaE domain to the small, electron-transferring
      subunit of the MBH completely abolished the export competence of the protein.
      Activity measurements revealed that the H(2) production capacity of the purified
      MBH(PsaE) fusion protein was very similar to that of wild-type MBH. In order to
      analyze the specific interaction of MBH(PsaE) with PS I, His-tagged PS I lacking
      the PsaE subunit was purified via Ni-nitrilotriacetic acid affinity and
      subsequent hydrophobic interaction chromatography. Formation of PS I-hydrogenase
      supercomplexes was demonstrated by blue native gel electrophoresis. The results
      indicate a vital prerequisite for the quantitative analysis of the MBH(PsaE)-PS I
      complex formation and its light-driven H(2) production capacity by means of
      spectroelectrochemistry.

PMID- 20154104
TI  - Effects of simulated Mars conditions on the survival and growth of Escherichia
      coli and Serratia liquefaciens.
AB  - Escherichia coli and Serratia liquefaciens, two bacterial spacecraft contaminants
      known to replicate under low atmospheric pressures of 2.5 kPa, were tested for
      growth and survival under simulated Mars conditions. Environmental stresses of
      high salinity, low temperature, and low pressure were screened alone and in
      combination for effects on bacterial survival and replication, and then cells
      were tested in Mars analog soils under simulated Mars conditions. Survival and
      replication of E. coli and S. liquefaciens cells in liquid medium were evaluated
      for 7 days under low temperatures (5, 10, 20, or 30 degrees C) with increasing
      concentrations (0, 5, 10, or 20%) of three salts (MgCl(2), MgSO(4), NaCl)
      reported to be present on the surface of Mars. Moderate to high growth rates were
      observed for E. coli and S. liquefaciens at 30 or 20 degrees C and in solutions
      with 0 or 5% salts. In contrast, cell densities of both species generally did not
      increase above initial inoculum levels under the highest salt concentrations (10
      and 20%) and the four temperatures tested, with the exception that moderately
      higher cell densities were observed for both species at 10% MgSO(4) maintained at
      20 or 30 degrees C. Growth rates of E. coli and S. liquefaciens in low salt
      concentrations were robust under all pressures (2.5, 10, or 101.3 kPa),
      exhibiting a general increase of up to 2.5 orders of magnitude above the initial
      inoculum levels of the assays. Vegetative E. coli cells were maintained in a Mars
      analog soil for 7 days under simulated Mars conditions that included temperatures
      between 20 and -50 degrees C for a day/night diurnal period, UVC irradiation (200
      to 280 nm) at 3.6 W m(-2) for daytime operations (8 h), pressures held at a
      constant 0.71 kPa, and a gas composition that included the top five gases found
      in the martian atmosphere. Cell densities of E. coli failed to increase under
      simulated Mars conditions, and survival was reduced 1 to 2 orders of magnitude by
      the interactive effects of desiccation, UV irradiation, high salinity, and low
      pressure (in decreasing order of importance). Results suggest that E. coli may be
      able to survive, but not grow, in surficial soils on Mars.

PMID- 20154105
TI  - Changes in denitrifier abundance, denitrification gene mRNA levels, nitrous oxide
      emissions, and denitrification in anoxic soil microcosms amended with glucose and
      plant residues.
AB  - In agricultural cropping systems, crop residues are sources of organic carbon
      (C), an important factor influencing denitrification. The effects of red clover,
      soybean, and barley plant residues and of glucose on denitrifier abundance,
      denitrification gene mRNA levels, nitrous oxide (N(2)O) emissions, and
      denitrification rates were quantified in anoxic soil microcosms for 72 h. nosZ
      gene abundances and mRNA levels significantly increased in response to all
      organic carbon treatments over time. In contrast, the abundance and mRNA levels
      of Pseudomonas mandelii and closely related species (nirS(P)) increased only in
      glucose-amended soil: the nirS(P) guild abundance increased 5-fold over the 72-h
      incubation period (P < 0.001), while the mRNA level significantly increased more
      than 15-fold at 12 h (P < 0.001) and then subsequently decreased. The nosZ gene
      abundance was greater in plant residue-amended soil than in glucose-amended soil.
      Although plant residue carbon-to-nitrogen (C:N) ratios varied from 15:1 to 30:1,
      nosZ gene and mRNA levels were not significantly different among plant residue
      treatments, with an average of 3.5 x 10(7) gene copies and 6.9 x 10(7)
      transcripts g(-1) dry soil. Cumulative N(2)O emissions and denitrification rates
      increased over 72 h in both glucose- and plant-tissue-C-treated soil. The nirS(P)
      and nosZ communities responded differently to glucose and plant residue
      amendments. However, the targeted denitrifier communities responded similarly to
      the different plant residues under the conditions tested despite changes in the
      quality of organic C and different C:N ratios.

PMID- 20154106
TI  - Distribution of virulence factors and molecular fingerprinting of Aeromonas
      species isolates from water and clinical samples: suggestive evidence of water-to
      human transmission.
AB  - A total of 227 isolates of Aeromonas obtained from different geographical
      locations in the United States and different parts of the world, including 28
      reference strains, were analyzed to determine the presence of various virulence
      factors. These isolates were also fingerprinted using biochemical identification
      and pulse-field gel electrophoresis (PFGE). Of these 227 isolates, 199 that were
      collected from water and clinical samples belonged to three major groups or
      complexes, namely, the A. hydrophila group, the A. caviae-A. media group, and the
      A. veronii-A. sobria group, based on biochemical profiles, and they had various
      pulsotypes. When virulence factor activities were examined, Aeromonas isolates
      obtained from clinical sources had higher cytotoxic activities than isolates
      obtained from water sources for all three Aeromonas species groups. Likewise, the
      production of quorum-sensing signaling molecules, such as N-acyl homoserine
      lactone, was greater in clinical isolates than in isolates from water for the A.
      caviae-A. media and A. hydrophila groups. Based on colony blot DNA hybridization,
      the heat-labile cytotonic enterotoxin gene and the DNA adenosine
      methyltransferase gene were more prevalent in clinical isolates than in water
      isolates for all three Aeromonas groups. Using colony blot DNA hybridization and
      PFGE, we obtained three sets of water and clinical isolates that had the same
      virulence signature and had indistinguishable PFGE patterns. In addition, all of
      these isolates belonged to the A. caviae-A. media group. The findings of the
      present study provide the first suggestive evidence of successful colonization
      and infection by particular strains of certain Aeromonas species after
      transmission from water to humans.

PMID- 20154107
TI  - Environmental determinants of and impact on childhood asthma by the bacterial
      community in household dust.
AB  - Asthma increased dramatically in the last decades of the 20th century and is
      representative of chronic diseases that have been linked to altered microbial
      exposure and immune responses. Here we evaluate the effects of environmental
      exposures typically associated with asthma protection or risk on the microbial
      community structure of household dust (dogs, cats, and day care). PCR-denaturing
      gradient gel analysis (PCR-DGGE) demonstrated that the bacterial community
      structure in house dust is significantly impacted by the presence of dogs or cats
      in the home (P = 0.0190 and 0.0029, respectively) and by whether or not children
      attend day care (P = 0.0037). In addition, significant differences in the dust
      bacterial community were associated with asthma outcomes in young children,
      including wheezing (P = 0.0103) and specific IgE (P = 0.0184). Our findings
      suggest that specific bacterial populations within the community are associated
      with either risk or protection from asthma.

PMID- 20154109
TI  - New vector system for random, single-step integration of multiple copies of DNA
      into the Rhodococcus genome.
AB  - We designed a new vector system for creating a random mutant library with
      multiple integrations of DNA fragments into the Rhodococcus genome in a single
      step. For this, we cotransformed two vectors into Rhodococcus by electroporation:
      pTip-istAB-sacB regulates the expression of the transposase (IstA) and its helper
      protein (IstB) under the influence of a thiostrepton-inducible promoter, and
      pRTSK-sacB provides the transposable-marker DNA. Both are multicopy vectors that
      are stable in the host cells; transposition of the transposable-marker DNA occurs
      only after the induction of IstA/IstB expression. With the addition of
      thiostrepton, all cultured cells harboring the two vectors, irrespective of the
      volume, can be mutated by random insertion of the transposable-marker DNA into
      their genome. Among the generated mutants examined, 30% showed multiple (two to
      five) insertion copies. The multiple integrated DNA copies were stable in the
      genome for more than 80 generations of serial growth without the addition of any
      selective antibiotics. This system can also be used for integrating various copy
      numbers of stably maintained protein expression cassettes in the host cell genome
      to modulate the expression level of biologically active recombinant proteins. We
      successfully applied this system to integrate multiple copies of expression
      cassettes for proline iminopeptidase and vitamin D(3) hydroxylase into the
      Rhodococcus genome and verified that the clones containing double or multiple
      copies of the integrated cassettes produced higher levels and showed higher
      enzymatic activities of the target protein than clones with only a single copy of
      integration.

PMID- 20154110
TI  - Identification and analysis of the biosynthetic gene cluster encoding the
      thiopeptide antibiotic cyclothiazomycin in Streptomyces hygroscopicus 10-22.
AB  - Thiopeptide antibiotics are an important class of natural products resulting from
      posttranslational modifications of ribosomally synthesized peptides.
      Cyclothiazomycin is a typical thiopeptide antibiotic that has a unique bridged
      macrocyclic structure derived from an 18-amino-acid structural peptide. Here we
      reported cloning, sequencing, and heterologous expression of the cyclothiazomycin
      biosynthetic gene cluster from Streptomyces hygroscopicus 10-22. Remarkably,
      successful heterologous expression of a 22.7-kb gene cluster in Streptomyces
      lividans 1326 suggested that there is a minimum set of 15 open reading frames
      that includes all of the functional genes required for cyclothiazomycin
      production. Six genes of these genes, cltBCDEFG flanking the structural gene
      cltA, were predicted to encode the enzymes required for the main framework of
      cyclothiazomycin, and two enzymes encoded by a putative operon, cltMN, were
      hypothesized to participate in the tailoring step to generate the tertiary
      thioether, leading to the final cyclization of the bridged macrocyclic structure.
      This rigorous bioinformatics analysis based on heterologous expression of
      cyclothiazomycin resulted in an ideal biosynthetic model for us to understand the
      biosynthesis of thiopeptides.

PMID- 20154111
TI  - Regulation of morphogenesis and biocontrol properties in Trichoderma virens by a
      VELVET protein, Vel1.
AB  - Mycoparasitic strains of Trichoderma are applied as commercial biofungicides for
      control of soilborne plant pathogens. Although the majority of commercial
      biofungicides are Trichoderma based, chemical pesticides, which are ecological
      and environmental hazards, still dominate the market. This is because
      biofungicides are not as effective or consistent as chemical fungicides. Efforts
      to improve these products have been limited by a lack of understanding of the
      genetic regulation of biocontrol activities. In this study, using gene knockout
      and complementation, we identified the VELVET protein Vel1 as a key regulator of
      biocontrol, as well as morphogenetic traits, in Trichoderma virens, a commercial
      biocontrol agent. Mutants with mutations in vel1 were defective in secondary
      metabolism (antibiosis), mycoparasitism, and biocontrol efficacy. In nutrient
      rich media they also lacked two types of spores important for survival and
      development of formulation products: conidia (on agar) and chlamydospores (in
      liquid shake cultures). These findings provide an opportunity for genetic
      enhancement of biocontrol and industrial strains of Trichoderma, since Vel1 is
      very highly conserved across three Trichoderma species.

PMID- 20154112
TI  - Role of Geobacter sulfurreducens outer surface c-type cytochromes in reduction of
      soil humic acid and anthraquinone-2,6-disulfonate.
AB  - Deleting individual genes for outer surface c-type cytochromes in Geobacter
      sulfurreducens partially inhibited the reduction of humic substances and
      anthraquinone-2,6,-disulfonate. Complete inhibition was obtained only when five
      of these genes were simultaneously deleted, suggesting that diverse outer surface
      cytochromes can contribute to the reduction of humic substances and other
      extracellular quinones.

PMID- 20154108
TI  - Census of the viral metagenome within an activated sludge microbial assemblage.
AB  - The viral metagenome within an activated sludge microbial assemblage was sampled
      using culture-dependent and culture-independent methods and compared to the
      diversity of activated sludge bacterial taxa. A total of 70 unique cultured
      bacterial isolates, 24 cultured bacteriophages, 829 bacterial metagenomic clones
      of 16S rRNA genes, and 1,161 viral metagenomic clones were subjected to a
      phylogenetic analysis.

PMID- 20154113
TI  - Sequence-based analysis of secondary-metabolite biosynthesis in marine
      actinobacteria.
AB  - A diverse collection of 60 marine-sediment-derived Actinobacteria representing 52
      operational taxonomic units was screened by PCR for genes associated with
      secondary-metabolite biosynthesis. Three primer sets were employed to
      specifically target adenylation domains associated with nonribosomal peptide
      synthetases (NRPSs) and ketosynthase (KS) domains associated with type I modular,
      iterative, hybrid, and enediyne polyketide synthases (PKSs). In total, two-thirds
      of the strains yielded a sequence-verified PCR product for at least one of these
      biosynthetic types. Genes associated with enediyne biosynthesis were detected in
      only two genera, while 88% of the ketosynthase sequences shared greatest homology
      with modular PKSs. Positive strains included representatives of families not
      traditionally associated with secondary-metabolite production, including the
      Corynebacteriaceae, Gordoniaceae, Intrasporangiaceae, and Micrococcaceae. In four
      of five cases where phylogenetic analyses of KS sequences revealed close
      evolutionary relationships to genes associated with experimentally characterized
      biosynthetic pathways, secondary-metabolite production was accurately predicted.
      Sequence clustering patterns were used to provide an estimate of PKS pathway
      diversity and to assess the biosynthetic richness of individual strains. The
      detection of highly similar KS sequences in distantly related strains provided
      evidence of horizontal gene transfer, while control experiments designed to
      amplify KS sequences from Salinispora arenicola strain CNS-205, for which a
      genome sequence is available, led to the detection of 70% of the targeted PKS
      pathways. The results provide a bioinformatic assessment of secondary-metabolite
      biosynthetic potential that can be applied in the absence of fully assembled
      pathways or genome sequences. The rapid identification of strains that possess
      the greatest potential to produce new secondary metabolites along with those that
      produce known compounds can be used to improve the process of natural-product
      discovery by providing a method to prioritize strains for fermentation studies
      and chemical analysis.

PMID- 20154114
TI  - Fermentation of glycerol to succinate by metabolically engineered strains of
      Escherichia coli.
AB  - The fermentative metabolism of Escherichia coli was reengineered to efficiently
      convert glycerol to succinate under anaerobic conditions without the use of
      foreign genes. Formate and ethanol were the dominant fermentation products from
      glycerol in wild-type Escherichia coli ATCC 8739, followed by succinate and
      acetate. Inactivation of pyruvate formate-lyase (pflB) in the wild-type strain
      eliminated the production of formate and ethanol and reduced the production of
      acetate. However, this deletion slowed growth and decreased cell yields due to
      either insufficient energy production or insufficient levels of electron
      acceptors. Reversing the direction of the gluconeogenic phosphoenolpyruvate
      carboxykinase reaction offered an approach to solve both problems, conserving
      energy as an additional ATP and increasing the pool of electron acceptors
      (fumarate and malate). Recruiting this enzyme through a promoter mutation (pck*)
      to increase expression also increased the rate of growth, cell yield, and
      succinate production. Presumably, the high NADH/NAD(+) ratio served to establish
      the direction of carbon flow. Additional mutations were also beneficial. Glycerol
      dehydrogenase and the phosphotransferase-dependent dihydroxyacetone kinase are
      regarded as the primary route for glycerol metabolism under anaerobic conditions.
      However, this is not true for succinate production by engineered strains.
      Deletion of the ptsI gene or any other gene essential for the phosphotranferase
      system was found to increase succinate yield. Deletion of pflB in this background
      provided a further increase in the succinate yield. Together, these three core
      mutations (pck*, ptsI, and pflB) effectively redirected carbon flow from glycerol
      to succinate at 80% of the maximum theoretical yield during anaerobic
      fermentation in mineral salts medium.

PMID- 20154115
TI  - Molecular epidemiology of Campylobacter jejuni in a geographically isolated
      country with a uniquely structured poultry industry.
AB  - In New Zealand the number of campylobacteriosis notifications increased markedly
      between 2000 and 2007. Notably, this country's poultry supply is different than
      that of many developed countries as the fresh and frozen poultry available at
      retail are exclusively of domestic origin. To examine the possible link between
      human cases and poultry, a sentinel surveillance site was established to study
      the molecular epidemiology of Campylobacter jejuni over a 3-year period from 2005
      to 2008 using multilocus sequence typing. Studies showed that 60.1 to 81.4% of
      retail poultry carcasses from the major suppliers were contaminated with C.
      jejuni. Differences were detected in the probability and level of contamination
      and the relative frequency of genotypes for individual poultry suppliers and
      humans. Some carcasses were contaminated with isolates belonging to more than one
      sequence type (ST), and there was evidence of both ubiquitous and supplier
      associated strains, an epidemiological pattern not recognized yet in other
      countries. The common poultry STs were also common in human clinical cases,
      providing evidence that poultry is a major contributor to human infection. Both
      internationally rare genotypes, such as ST-3069 and ST-474, and common genotypes,
      such as ST-45 and ST-48, were identified in this study. The dominant human
      sequence type in New Zealand, ST-474, was found almost exclusively in isolates
      from one poultry supplier, which provided evidence that C. jejuni has a
      distinctive molecular epidemiology in this country. These results may be due in
      part to New Zealand's geographical isolation and its uniquely structured poultry
      industry.

PMID- 20154116
TI  - Stable isotope probing analysis of interactions between ammonia oxidizers.
AB  - The response of natural microbial communities to environmental change can be
      assessed by determining DNA- or RNA-targeted changes in relative abundance of 16S
      rRNA gene sequences by using fingerprinting techniques such as denaturing
      gradient gel electrophoresis (DNA-DGGE and RNA-DGGE, respectively) or by stable
      isotope probing (SIP) of 16S rRNA genes following incubation with a (13)C-labeled
      substrate (DNA-SIP-DGGE). The sensitivities of these three approaches were
      compared during batch growth of communities containing two or three Nitrosospira
      pure or enriched cultures with different tolerances to a high ammonia
      concentration. Cultures were supplied with low, intermediate, or high initial
      ammonia concentrations and with (13)C-labeled carbon dioxide. DNA-SIP-DGGE
      provided the most direct evidence for growth and was the most sensitive, with
      changes in DGGE profiles evident before changes in DNA- and RNA-DGGE profiles and
      before detectable increases in nitrite and nitrate production. RNA-DGGE provided
      intermediate sensitivity. In addition, the three molecular methods were used to
      follow growth of individual strains within communities. In general, changes in
      relative activities of individual strains within communities could be predicted
      from monoculture growth characteristics. Ammonia-tolerant Nitrosospira cluster 3b
      strains dominated mixed communities at all ammonia concentrations, and ammonia
      sensitive strains were outcompeted at an intermediate ammonia concentration.
      However, coexistence of ammonia-tolerant and ammonia-sensitive strains occurred
      at the lowest ammonia concentration, and, under some conditions, strains
      inhibited at high ammonia in monoculture were active at high ammonia in mixed
      cultures, where they coexisted with ammonia-tolerant strains. The results
      therefore demonstrate the sensitivity of SIP for detection of activity of
      organisms with relatively low yield and low activity and its ability to follow
      changes in the structure of interacting microbial communities.

PMID- 20154117
TI  - Polyphasic analyses of methanogenic archaeal communities in agricultural biogas
      plants.
AB  - Knowledge of the microbial consortia participating in the generation of biogas,
      especially in methane formation, is still limited. To overcome this limitation,
      the methanogenic archaeal communities in six full-scale biogas plants supplied
      with different liquid manures and renewable raw materials as substrates were
      analyzed by a polyphasic approach. Fluorescence in situ hybridization (FISH) was
      carried out to quantify the methanogenic Archaea in the reactor samples. In
      addition, quantitative real-time PCR (Q-PCR) was used to support and complete the
      FISH analysis. Five of the six biogas reactors were dominated by hydrogenotrophic
      Methanomicrobiales. The average values were between 60 to 63% of archaeal cell
      counts (FISH) and 61 to 99% of archaeal 16S rRNA gene copies (Q-PCR). Within this
      order, Methanoculleus was found to be the predominant genus as determined by
      amplified rRNA gene restriction analysis. The aceticlastic family
      Methanosaetaceae was determined to be the dominant methanogenic group in only one
      biogas reactor, with average values for Q-PCR and FISH between 64% and 72%.
      Additionally, in three biogas reactors hitherto uncharacterized but potentially
      methanogenic species were detected. They showed closest accordance with
      nucleotide sequences of the hitherto unclassified CA-11 (85%) and ARC-I (98%)
      clusters. These results point to hydrogenotrophic methanogenesis as a predominant
      pathway for methane synthesis in five of the six analyzed biogas plants. In
      addition, a correlation between the absence of Methanosaetaceae in the biogas
      reactors and high concentrations of total ammonia (sum of NH(3) and NH(4)(+)) was
      observed.

PMID- 20154118
TI  - Laccase and its role in production of extracellular reactive oxygen species
      during wood decay by the brown rot basidiomycete Postia placenta.
AB  - Brown rot basidiomycetes initiate wood decay by producing extracellular reactive
      oxygen species that depolymerize the structural polysaccharides of
      lignocellulose. Secreted fungal hydroquinones are considered one contributor
      because they have been shown to reduce Fe(3+), thus generating perhydroxyl
      radicals and Fe(2+), which subsequently react further to produce biodegradative
      hydroxyl radicals. However, many brown rot fungi also secrete high levels of
      oxalate, which chelates Fe(3+) tightly, making it unreactive with hydroquinones.
      For hydroquinone-driven hydroxyl radical production to contribute in this
      environment, an alternative mechanism to oxidize hydroquinones is required. We
      show here that aspen wood undergoing decay by the oxalate producer Postia
      placenta contained both 2,5-dimethoxyhydroquinone and laccase activity. Mass
      spectrometric analysis of proteins extracted from the wood identified a putative
      laccase (Joint Genome Institute P. placenta protein identification number
      111314), and heterologous expression of the corresponding gene confirmed this
      assignment. Ultrafiltration experiments with liquid pressed from the biodegrading
      wood showed that a high-molecular-weight component was required for it to oxidize
      2,5-dimethoxyhydroquinone rapidly and that this component was replaceable by P.
      placenta laccase. The purified laccase oxidized 2,5-dimethoxyhydroquinone with a
      second-order rate constant near 10(4) M(-1) s(-1), and measurements of the
      H(2)O(2) produced indicated that approximately one perhydroxyl radical was
      generated per hydroquinone supplied. Using these values and a previously
      developed computer model, we estimate that the quantity of reactive oxygen
      species produced by P. placenta laccase in wood is large enough that it likely
      contributes to incipient decay.

PMID- 20154119
TI  - The genome sequence of Psychrobacter arcticus 273-4, a psychroactive Siberian
      permafrost bacterium, reveals mechanisms for adaptation to low-temperature
      growth.
AB  - Psychrobacter arcticus strain 273-4, which grows at temperatures as low as -10
      degrees C, is the first cold-adapted bacterium from a terrestrial environment
      whose genome was sequenced. Analysis of the 2.65-Mb genome suggested that some of
      the strategies employed by P. arcticus 273-4 for survival under cold and stress
      conditions are changes in membrane composition, synthesis of cold shock proteins,
      and the use of acetate as an energy source. Comparative genome analysis indicated
      that in a significant portion of the P. arcticus proteome there is reduced use of
      the acidic amino acids and proline and arginine, which is consistent with
      increased protein flexibility at low temperatures. Differential amino acid usage
      occurred in all gene categories, but it was more common in gene categories
      essential for cell growth and reproduction, suggesting that P. arcticus evolved
      to grow at low temperatures. Amino acid adaptations and the gene content likely
      evolved in response to the long-term freezing temperatures (-10 degrees C to -12
      degrees C) of the Kolyma (Siberia) permafrost soil from which this strain was
      isolated. Intracellular water likely does not freeze at these in situ
      temperatures, which allows P. arcticus to live at subzero temperatures.

PMID- 20154120
TI  - Isolation of novel extreme-tolerant cyanobacteria from a rock-dwelling microbial
      community by using exposure to low Earth orbit.
AB  - Many cyanobacteria are known to tolerate environmental extremes. Motivated by an
      interest in selecting cyanobacteria for applications in space, we launched rocks
      from a limestone cliff in Beer, Devon, United Kingdom, containing an epilithic
      and endolithic rock-dwelling community of cyanobacteria into low Earth orbit
      (LEO) at a height of approximately 300 kilometers. The community was exposed for
      10 days to isolate cyanobacteria that can survive exposure to the extreme
      radiation and desiccating conditions associated with space. Culture-independent
      (16S rRNA) and culture-dependent methods showed that the cyanobacterial community
      was composed of Pleurocapsales, Oscillatoriales, and Chroococcales. A single
      cyanobacterium, a previously uncharacterized extremophile, was isolated after
      exposure to LEO. We were able to isolate the cyanobacterium from the limestone
      cliff after exposing the rock-dwelling community to desiccation and vacuum (0.7 x
      10(-3) kPa) in the laboratory. The ability of the organism to survive the
      conditions in space may be linked to the formation of dense colonies. These
      experiments show how extreme environmental conditions, including space, can be
      used to select for novel microorganisms. Furthermore, it improves our knowledge
      of environmental tolerances of extremophilic rock-dwelling cyanobacteria.

PMID- 20154121
TI  - Experimental adaptation of Burkholderia cenocepacia to onion medium reduces host
      range.
AB  - It is unclear whether adaptation to a new host typically broadens or compromises
      host range, yet the answer bears on the fate of emergent pathogens and symbionts.
      We investigated this dynamic using a soil isolate of Burkholderia cenocepacia, a
      species that normally inhabits the rhizosphere, is related to the onion pathogen
      B. cepacia, and can infect the lungs of cystic fibrosis patients. We hypothesized
      that adaptation of B. cenocepacia to a novel host would compromise fitness and
      virulence in alternative hosts. We modeled adaptation to a specific host by
      experimentally evolving 12 populations of B. cenocepacia in liquid medium
      composed of macerated onion tissue for 1,000 generations. The mean fitness of all
      populations increased by 78% relative to the ancestor, but significant variation
      among lines was observed. Populations also varied in several phenotypes related
      to host association, including motility, biofilm formation, and quorum-sensing
      function. Together, these results suggest that each population adapted by fixing
      different sets of adaptive mutations. However, this adaptation was consistently
      accompanied by a loss of pathogenicity to the nematode Caenorhabditis elegans; by
      500 generations most populations became unable to kill nematodes. In conclusion,
      we observed a narrowing of host range as a consequence of prolonged adaptation to
      an environment simulating a specific host, and we suggest that emergent pathogens
      may face similar consequences if they become host-restricted.

PMID- 20154122
TI  - Characterization of environmentally persistent Escherichia coli isolates leached
      from an Irish soil.
AB  - Soils are typically considered to be suboptimal environments for enteric
      organisms, but there is increasing evidence that Escherichia coli populations can
      become resident in soil under favorable conditions. Previous work reported the
      growth of autochthonous E. coli in a maritime temperate Luvic Stagnosol soil, and
      this study aimed to characterize, by molecular and physiological means, the
      genetic diversity and physiology of environmentally persistent E. coli isolates
      leached from the soil. Molecular analysis (16S rRNA sequencing, enterobacterial
      repetitive intergenic consensus PCR, pulsed-field gel electrophoresis, and a
      multiplex PCR method) established the genetic diversity of the isolates (n = 7),
      while physiological methods determined the metabolic capability and environmental
      fitness of the isolates, relative to those of laboratory strains, under the
      conditions tested. Genotypic analysis indicated that the leached isolates do not
      form a single genetic grouping but that multiple genotypic groups are capable of
      surviving and proliferating in this environment. In physiological studies,
      environmental isolates grew well across a broad range of temperatures and media,
      in comparison with the growth of laboratory strains. These findings suggest that
      certain E. coli strains may have the ability to colonize and adapt to soil
      conditions. The resulting lack of fecal specificity has implications for the use
      of E. coli as an indicator of fecal pollution in the environment.

PMID- 20154123
TI  - Di-adenosine tetraphosphate (Ap4A) metabolism impacts biofilm formation by
      Pseudomonas fluorescens via modulation of c-di-GMP-dependent pathways.
AB  - Dinucleoside tetraphosphates are common constituents of the cell and are thought
      to play diverse biological roles in organisms ranging from bacteria to humans. In
      this study we characterized two independent mechanisms by which di-adenosine
      tetraphosphate (Ap4A) metabolism impacts biofilm formation by Pseudomonas
      fluorescens. Null mutations in apaH, the gene encoding nucleoside tetraphosphate
      hydrolase, resulted in a marked increase in the cellular level of Ap4A.
      Concomitant with this increase, Pho regulon activation in low-inorganic-phosphate
      (P(i)) conditions was severely compromised. As a consequence, an apaH mutant was
      not sensitive to Pho regulon-dependent inhibition of biofilm formation. In
      addition, we characterized a Pho-independent role for Ap4A metabolism in
      regulation of biofilm formation. In P(i)-replete conditions Ap4A metabolism was
      found to impact expression and localization of LapA, the major adhesin regulating
      surface commitment by P. fluorescens. Increases in the level of c-di-GMP in the
      apaH mutant provided a likely explanation for increased localization of LapA to
      the outer membrane in response to elevated Ap4A concentrations. Increased levels
      of c-di-GMP in the apaH mutant were associated with increases in the level of
      GTP, suggesting that elevated levels of Ap4A may promote de novo purine
      biosynthesis. In support of this suggestion, supplementation with adenine could
      partially suppress the biofilm and c-di-GMP phenotypes of the apaH mutant. We
      hypothesize that changes in the substrate (GTP) concentration mediated by altered
      flux through nucleotide biosynthetic pathways may be a significant point of
      regulation for c-di-GMP biosynthesis and regulation of biofilm formation.

PMID- 20154124
TI  - The twists and turns of enzyme function.

PMID- 20154126
TI  - Organization of the electron transfer chain to oxygen in the obligate human
      pathogen Neisseria gonorrhoeae: roles for cytochromes c4 and c5, but not
      cytochrome c2, in oxygen reduction.
AB  - Although Neisseria gonorrhoeae is a prolific source of eight c-type cytochromes,
      little is known about how its electron transfer pathways to oxygen are organized.
      In this study, the roles in the respiratory chain to oxygen of cytochromes c(2),
      c(4), and c(5), encoded by the genes cccA, cycA, and cycB, respectively, have
      been investigated. Single mutations in genes for either cytochrome c(4) or c(5)
      resulted in an increased sensitivity to growth inhibition by excess oxygen and
      small decreases in the respiratory capacity of the parent, which were
      complemented by the chromosomal integration of an ectopic, isopropyl-beta-d
      thiogalactopyranoside (IPTG)-inducible copy of the cycA or cycB gene. In
      contrast, a cccA mutant reduced oxygen slightly more rapidly than the parent,
      suggesting that cccA is expressed but cytochrome c(2) is not involved in electron
      transfer to cytochrome oxidase. The deletion of cccA increased the sensitivity of
      the cycB mutant to excess oxygen but decreased the sensitivity of the cycA
      mutant. Despite many attempts, a double mutant defective in both cytochromes c(4)
      and c(5) could not be isolated. However, a strain with the ectopically encoded,
      IPTG-inducible cycB gene with deletions in both cycA and cycB was constructed:
      the growth and survival of this strain were dependent upon the addition of IPTG,
      so gonococcal survival is dependent upon the synthesis of either cytochrome c(4)
      or c(5). These results define the gonococcal electron transfer chain to oxygen in
      which cytochromes c(4) and c(5), but not cytochrome c(2), provide alternative
      pathways for electron transfer from the cytochrome bc(1) complex to the terminal
      oxidase cytochrome cbb(3).

PMID- 20154125
TI  - Analysis of protein expression regulated by the Helicobacter pylori ArsRS two
      component signal transduction system.
AB  - Previous studies have shown that the Helicobacter pylori ArsRS two-component
      signal transduction system contributes to acid-responsive gene expression. To
      identify additional members of the ArsRS regulon and further investigate the
      regulatory role of the ArsRS system, we analyzed protein expression in wild-type
      and arsS null mutant strains. Numerous proteins were differentially expressed in
      an arsS mutant strain compared to a wild-type strain when the bacteria were
      cultured at pH 5.0 and also when they were cultured at pH 7.0. Genes encoding 14
      of these proteins were directly regulated by the ArsRS system, based on observed
      binding of ArsR to the relevant promoter regions. The ArsRS-regulated proteins
      identified in this study contribute to acid resistance (urease and amidase),
      acetone metabolism (acetone carboxylase), resistance to oxidative stress
      (thioredoxin reductase), quorum sensing (Pfs), and several other functions. These
      results provide further definition of the ArsRS regulon and underscore the
      importance of the ArsRS system in regulating expression of H. pylori proteins
      during bacterial growth at both neutral pH and acidic pH.

PMID- 20154127
TI  - Cell surface xylanases of the glycoside hydrolase family 10 are essential for
      xylan utilization by Paenibacillus sp. W-61 as generators of xylo-oligosaccharide
      inducers for the xylanase genes.
AB  - Paenibacillus sp. W-61 is capable of utilizing water-insoluble xylan for carbon
      and energy sources and has three xylanase genes, xyn1, xyn3, and xyn5. Xyn1,
      Xyn3, and Xyn5 are extracellular enzymes of the glycoside hydrolase (GH) families
      11, 30, and 10, respectively. Xyn5 contains several domains including those of
      carbohydrate-binding modules (CBMs) similar to a surface-layer homologous (SLH)
      protein. This study focused on the role of Xyn5, localized on the cell surface,
      in water-insoluble xylan utilization. Electron microscopy using immunogold
      staining revealed Xyn5 clusters over the entire cell surface. Xyn5 was bound to
      cell wall fractions through its SLH domain. A Deltaxyn5 mutant grew poorly and
      produced minimal amounts of Xyn1 and Xyn3 on water-insoluble xylan. A Xyn5 mutant
      lacking the SLH domain (Xyn5DeltaSLH) grew poorly, secreting Xyn5DeltaSLH into
      the medium and producing minimal Xyn1 and Xyn3 on water-insoluble xylan. A mutant
      with an intact xyn5 produced Xyn5 on the cell surface, grew normally, and
      actively synthesized Xyn1 and Xyn3 on water-insoluble xylan. Quantitative reverse
      transcription-PCR showed that xylobiose, generated from water-insoluble xylan
      decomposition by Xyn5, is the most active inducer for xyn1 and xyn3. Luciferase
      assays using a Xyn5-luciferase fusion protein suggested that xylotriose is the
      best inducer for xyn5. The cell surface Xyn5 appears to play two essential roles
      in water-insoluble xylan utilization: (i) generation of the xylo-oligosaccharide
      inducers of all the xyn genes from water-insoluble xylan and (ii) attachment of
      the cells to the substrate so that the generated inducers can be immediately
      taken up by cells to activate expression of the xyn system.

PMID- 20154128
TI  - Dual control of Sinorhizobium meliloti RpoE2 sigma factor activity by two PhyR
      type two-component response regulators.
AB  - RpoE2 is an extracytoplasmic function (ECF) sigma factor involved in the general
      stress response of Sinorhizobium meliloti, the nitrogen-fixing symbiont of the
      legume plant alfalfa. RpoE2 orthologues are widely found among
      alphaproteobacteria, where they play various roles in stress resistance and/or
      host colonization. In this paper, we report a genetic and biochemical
      investigation of the mechanisms of signal transduction leading to S. meliloti
      RpoE2 activation in response to stress. We showed that RpoE2 activity is
      negatively controlled by two paralogous anti-sigma factors, RsiA1 (SMc01505) and
      RsiA2 (SMc04884), and that RpoE2 activation by stress requires two redundant
      paralogous PhyR-type response regulators, RsiB1 (SMc01504) and RsiB2 (SMc00794).
      RsiB1 and RsiB2 do not act at the level of rpoE2 transcription but instead
      interact with the anti-sigma factors, and we therefore propose that they act as
      anti-anti-sigma factors to relieve RpoE2 inhibition in response to stress. This
      model closely resembles a recently proposed model of activation of RpoE2-like
      sigma factors in Methylobacterium extorquens and Bradyrhizobium japonicum, but
      the existence of two pairs of anti- and anti-anti-sigma factors in S. meliloti
      adds an unexpected level of complexity, which may allow the regulatory system to
      integrate multiple stimuli.

PMID- 20154129
TI  - Increase in rhamnolipid synthesis under iron-limiting conditions influences
      surface motility and biofilm formation in Pseudomonas aeruginosa.
AB  - Iron is an essential element for life but also serves as an environmental signal
      for biofilm development in the opportunistic human pathogen Pseudomonas
      aeruginosa. Under iron-limiting conditions, P. aeruginosa displays enhanced
      twitching motility and forms flat unstructured biofilms. In this study, we
      present evidence suggesting that iron-regulated production of the biosurfactant
      rhamnolipid is important to facilitate the formation of flat unstructured
      biofilms. We show that under iron limitation the timing of rhamnolipid expression
      is shifted to the initial stages of biofilm formation (versus later in biofilm
      development under iron-replete conditions) and results in increased bacterial
      surface motility. In support of this observation, an rhlAB mutant defective in
      biosurfactant production showed less surface motility under iron-restricted
      conditions and developed structured biofilms similar to those developed by the
      wild type under iron-replete conditions. These results highlight the importance
      of biosurfactant production in determining the mature structure of P. aeruginosa
      biofilms under iron-limiting conditions.

PMID- 20154130
TI  - Central role of the early colonizer Veillonella sp. in establishing multispecies
      biofilm communities with initial, middle, and late colonizers of enamel.
AB  - Human dental biofilm communities comprise several species, which can interact
      cooperatively or competitively. Bacterial interactions influence biofilm
      formation, metabolic changes, and physiological function of the community. Lactic
      acid, a common metabolite of oral bacteria, was measured in the flow cell
      effluent of one-, two- and three-species communities growing on saliva as the
      sole nutritional source. We investigated single-species and multispecies
      colonization by using known initial, early, middle, and late colonizers of
      enamel. Fluorescent-antibody staining and image analysis were used to quantify
      the biomass in saliva-fed flow cells. Of six species tested, only the initial
      colonizer Actinomyces oris exhibited significant growth. The initial colonizer
      Streptococcus oralis produced lactic acid but showed no significant growth. The
      early colonizer Veillonella sp. utilized lactic acid in two- and three-species
      biofilm communities. The biovolumes of all two-species biofilms increased when
      Veillonella sp. was present as one of the partners, indicating that this early
      colonizer promotes mutualistic community development. All three-species
      combinations exhibited enhanced growth except one, i.e., A. oris, Veillonella
      sp., and the middle colonizer Porphyromonas gingivalis, indicating specificity
      among three-species communities. Further specificity was seen when Fusobacterium
      nucleatum (a middle colonizer), Aggregatibacter actinomycetemcomitans (a late
      colonizer), and P. gingivalis did not grow with S. oralis in two-species
      biofilms, but inclusion of Veillonella sp. resulted in growth of all three
      species combinations. We propose that commensal veillonellae use lactic acid for
      growth in saliva and that they communicate metabolically with initial, early,
      middle, and late colonizers to establish multispecies communities on enamel.

PMID- 20154131
TI  - Heterochronic phosphorelay gene expression as a source of heterogeneity in
      Bacillus subtilis spore formation.
AB  - In response to limiting nutrient sources and cell density signals, Bacillus
      subtilis can differentiate and form highly resistant endospores. Initiation of
      spore development is governed by the master regulator Spo0A, which is activated
      by phosphorylation via a multicomponent phosphorelay. Interestingly, only part of
      a clonal population will enter this developmental pathway, a phenomenon known as
      sporulation bistability or sporulation heterogeneity. How sporulation
      heterogeneity is established is largely unknown. To investigate the origins of
      sporulation heterogeneity, we constructed promoter-green fluorescent protein
      (GFP) fusions to the main phosphorelay genes and perturbed their expression
      levels. Using time-lapse fluorescence microscopy and flow cytometry, we showed
      that expression of the phosphorelay genes is distributed in a unimodal manner.
      However, single-cell trajectories revealed that phosphorelay gene expression is
      highly dynamic or "heterochronic" between individual cells and that stochasticity
      of phosphorelay gene transcription might be an important regulatory mechanism for
      sporulation heterogeneity. Furthermore, we showed that artificial induction or
      depletion of the phosphorelay phosphate flow results in loss of sporulation
      heterogeneity. Our data suggest that sporulation heterogeneity originates from
      highly dynamic and variable gene activity of the phosphorelay components,
      resulting in large cell-to-cell variability with regard to phosphate input into
      the system. These transcriptional and posttranslational differences in
      phosphorelay activity appear to be sufficient to generate a heterogeneous
      sporulation signal without the need of the positive-feedback loop established by
      the sigma factor SigH.

PMID- 20154132
TI  - Protecting against antimicrobial effectors in the phagosome allows SodCII to
      contribute to virulence in Salmonella enterica serovar Typhimurium.
AB  - Salmonella enterica serovar Typhimurium replicates in macrophages, where it is
      subjected to antimicrobial substances, including superoxide, antimicrobial
      peptides, and proteases. The bacterium produces two periplasmic superoxide
      dismutases, SodCI and SodCII. Although both are expressed during infection, only
      SodCI contributes to virulence in the mouse by combating phagocytic superoxide.
      The differential contribution to virulence is at least partially due to inherent
      differences in the SodCI and SodCII proteins that are independent of enzymatic
      activity. SodCII is protease sensitive, and like other periplasmic proteins, it
      is released by osmotic shock. In contrast, SodCI is protease resistant and is
      retained within the periplasm after osmotic shock, a phenomenon that we term
      "tethering." We hypothesize that in the macrophage, antimicrobial peptides
      transiently disrupt the outer membrane. SodCII is released and/or phagocytic
      proteases gain access to the periplasm, and SodCII is degraded. SodCI is tethered
      within the periplasm and is protease resistant, thereby remaining to combat
      superoxide. Here we test aspects of this model. SodCII was released by the
      antimicrobial peptide polymyxin B or a mouse macrophage antimicrobial peptide
      (CRAMP), while SodCI remained tethered within the periplasm. A Salmonella pmrA
      constitutive mutant no longer released SodCII in vitro. Moreover, in the
      constitutive pmrA background, SodCII could contribute to survival of Salmonella
      during infection. SodCII also provided a virulence benefit in mice genetically
      defective in production of CRAMP. Thus, consistent with our model, protecting the
      outer membrane against antimicrobial peptides allows SodCII to contribute to
      virulence in vivo. These data also suggest direct in vivo cooperative
      interactions between macrophage antimicrobial effectors.

PMID- 20154133
TI  - Role of FlgT in anchoring the flagellum of Vibrio cholerae.
AB  - Flagellar motility has long been regarded as an important virulence factor. In
      Vibrio cholerae, the single polar flagellum is essential for motility as well as
      for proper attachment and colonization. In this study, we demonstrate that the
      novel flagellar protein FlgT is involved in anchoring the flagellum to the V.
      cholerae cell. A screen for novel colonization factors by use of TnphoA
      mutagenesis identified flgT. An in-frame deletion of flgT established that FlgT
      is required for attachment, colonization, and motility. Transmission electron
      microscopy revealed that while the flgT mutant is capable of assembling a
      phenotypically normal flagellum, the flgT population is mostly aflagellate
      compared to the wild-type population. Further analyses indicated that the
      flagellum of the flgT mutant is released into the culture supernatant from the
      cell upon completion of assembly. Additionally, hook basal body complexes appear
      to be released along with the filament. These results indicate that FlgT
      functions to stabilize the flagellar apparatus at the pole of the cell.

PMID- 20154134
TI  - Polymyxin B resistance in El Tor Vibrio cholerae requires lipid acylation
      catalyzed by MsbB.
AB  - Antimicrobial peptides are critical for innate antibacterial defense. Both Gram
      negative and Gram-positive microbes have mechanisms to alter their surfaces and
      resist killing by antimicrobial peptides. In Vibrio cholerae, two natural
      epidemic biotypes, classical and El Tor, exhibit distinct phenotypes with respect
      to sensitivity to the peptide antibiotic polymyxin B: classical strains are
      sensitive and El Tor strains are relatively resistant. We carried out mutant
      screens of both biotypes, aiming to identify classical V. cholerae mutants
      resistant to polymyxin B and El Tor V. cholerae mutants sensitive to polymyxin B.
      Insertions in a gene annotated msbB (encoding a predicted lipid A secondary
      acyltransferase) answered both screens, implicating its activity in antimicrobial
      peptide resistance of V. cholerae. Analysis of a defined mutation in the El Tor
      biotype demonstrated that msbB is required for resistance to all antimicrobial
      peptides tested. Mutation of msbB in a classical strain resulted in reduced
      resistance to several antimicrobial peptides but in no significant change in
      resistance to polymyxin B. msbB mutants of both biotypes showed decreased
      colonization of infant mice, with a more pronounced defect observed for the El
      Tor mutant. Mass spectrometry analysis showed that lipid A of the msbB mutant for
      both biotypes was underacylated compared to lipid A of the wild-type isolates,
      confirming that MsbB is a functional acyltransferase in V. cholerae.

PMID- 20154136
TI  - The second extracellular loop of pore-forming subunits of ATP-binding cassette
      transporters for basic amino acids plays a crucial role in interaction with the
      cognate solute binding protein(s).
AB  - In the thermophile Geobacillus stearothermophilus, the uptake of basic amino
      acids is mediated by an ABC transporter composed of the substrate binding protein
      (receptor) ArtJ and a homodimer each of the pore-forming subunit, ArtM, and the
      nucleotide-binding subunit, ArtP. We recently identified two putative binding
      sites in ArtJ that might interact with the Art(MP)(2) complex, thereby initiating
      the transport cycle (A. Vahedi-Faridi et al., J. Mol. Biol. 375:448-459, 2008).
      Here we investigated the contribution of charged amino acid residues in the
      second extracellular loop of ArtM to contact with ArtJ. Our results demonstrate a
      crucial role for residues K177, R185, and E188, since mutations to oppositely
      charged amino acids or glutamine led to a complete loss of ArtJ-stimulated ATPase
      activity of the complex variants in proteoliposomes. The defects could not be
      suppressed by ArtJ variants carrying mutations in site I (K39E and K152E) or II
      (E163K and D170K), suggesting a more complex interplay than that by a single salt
      bridge. These findings were supported by cross-linking assays demonstrating
      physical proximity between ArtJ(N166C) and ArtM(E182C). The importance of
      positively charged residues for receptor-transporter interaction was underscored
      by mutational analysis of the closely related transporter HisJ/LAO-HisQMP(2) of
      Salmonella enterica serovar Typhimurium. While transporter variants with mutated
      positively charged residues in HisQ displayed residual ATPase activities,
      corresponding mutants of HisM could no longer be stimulated by HisJ/LAO.
      Interestingly, the ATPase activity of the HisQM(K187E)P(2) variant was inhibited
      by l- and d-histidine in detergent, suggesting a role of the residue in
      preventing free histidine from gaining access to the substrate binding site
      within HisQM.

PMID- 20154135
TI  - Strains of the East Asian (W/Beijing) lineage of Mycobacterium tuberculosis are
      DosS/DosT-DosR two-component regulatory system natural mutants.
AB  - As part of our ongoing efforts to uncover the phenotypic consequences of genetic
      variability among clinical Mycobacterium tuberculosis isolates, we previously
      reported that isolates of the "East Asian" or "W/Beijing" lineage constitutively
      overexpress the coordinately regulated transcriptional program known as the DosR
      regulon under standard in vitro conditions. This phenotype distinguishes the
      W/Beijing lineage from all other M. tuberculosis lineages, which normally induce
      expression of this regulon only once exposed to low oxygen or nitric oxide, both
      of which result in inhibition of bacterial respiration and replication.
      Transcription of the DosR regulon is controlled through a two-component
      regulatory system comprising the transcription factor DosR and two possible
      cognate histidine sensor kinases, DosS and DosT. Through sequence analysis of a
      carefully selected set of isolates representing each of the major M. tuberculosis
      lineages, we describe herein a naturally occurring frameshift mutation in the
      gene encoding the DosT sensor kinase for isolates of the most recently evolved
      W/Beijing sublineages. Intriguingly, the occurrence of the frameshift mutation
      correlates precisely with the appearance of the constitutive DosR regulon
      phenotype displayed by the same "modern" W/Beijing strains. However,
      complementation studies have revealed that the mutation in dosT alone is not
      directly responsible for the constitutive DosR regulon phenotype. Our data serve
      to highlight the evolutionary pressure that exists among distinct M. tuberculosis
      lineages to maintain tight control over DosR regulon expression.

PMID- 20154137
TI  - The abi proteins and their involvement in bacteriocin self-immunity.
AB  - The Abi protein family consists of putative membrane-bound metalloproteases.
      While they are involved in membrane anchoring of proteins in eukaryotes, little
      is known about their function in prokaryotes. In some known bacteriocin loci, Abi
      genes have been found downstream of bacteriocin structural genes (e.g., pln locus
      from Lactobacillus plantarum and sag locus from Streptococcus pyogenes), where
      they probably are involved in self-immunity. By modifying the profile hidden
      Markov model used to select Abi proteins in the Pfam protein family database, we
      show that this family is larger than presently recognized. Using bacteriocin
      associated Abi genes as a means to search for novel bacteriocins in sequenced
      genomes, seven new bacteriocin-like loci were identified in Gram-positive
      bacteria. One such locus, from Lactobacillus sakei 23K, was selected for further
      experimental study, and it was confirmed that the bacteriocin-like genes (skkAB)
      exhibited antimicrobial activity when expressed in a heterologous host and that
      the associated Abi gene (skkI) conferred immunity against the cognate
      bacteriocin. Similar investigation of the Abi gene plnI and the Abi-like gene
      plnL from L. plantarum also confirmed their involvement in immunity to their
      cognate bacteriocins (PlnEF and PlnJK, respectively). Interestingly, the immunity
      genes from these three systems conferred a high degree of cross-immunity against
      each other's bacteriocins, suggesting the recognition of a common receptor. Site
      directed mutagenesis demonstrated that the conserved motifs constituting the
      putative proteolytic active site of the Abi proteins are essential for the
      immunity function of SkkI, and to our knowledge, this represents a new concept in
      self-immunity.

PMID- 20154138
TI  - Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination.
AB  - In order to balance the cellular requirements for copper with its toxic
      properties, an elegant set of mechanisms has evolved to regulate and buffer
      intracellular copper. The X-linked inhibitor of apoptosis (XIAP) protein was
      recently identified as a copper-binding protein and regulator of copper
      homeostasis, although the mechanism by which XIAP binds copper in the cytosol is
      unclear. Here we describe the identification of the copper chaperone for
      superoxide dismutase (CCS) as a mediator of copper delivery to XIAP in cells. We
      also find that CCS is a target of the E3 ubiquitin ligase activity of XIAP,
      although interestingly, ubiquitination of CCS by XIAP was found to lead to
      enhancement of its chaperone activity toward its physiologic target, superoxide
      dismutase 1, rather than proteasomal degradation. Collectively, our results
      reveal novel links among apoptosis, copper metabolism, and redox regulation
      through the XIAP-CCS complex.

PMID- 20154139
TI  - A novel conserved phosphotyrosine motif in the Drosophila fibroblast growth
      factor signaling adaptor Dof with a redundant role in signal transmission.
AB  - The fibroblast growth factor receptor (FGFR) signals through adaptors
      constitutively associated with the receptor. In Drosophila melanogaster, the FGFR
      specific adaptor protein Downstream-of-FGFR (Dof) becomes phosphorylated upon
      receptor activation at several tyrosine residues, one of which recruits Corkscrew
      (Csw), the Drosophila homolog of SHP2, which provides a molecular link to mitogen
      activated protein kinase (MAPK) activation. However, the Csw pathway is not the
      only link from Dof to MAPK. In this study, we identify a novel phosphotyrosine
      motif present in four copies in Dof and also found in other insect and vertebrate
      signaling molecules. We show that these motifs are phosphorylated and contribute
      to FGF signal transduction. They constitute one of three sets of phosphotyrosines
      that act redundantly in signal transmission: (i) a Csw binding site, (ii) four
      consensus Grb2 recognition sites, and (iii) four novel tyrosine motifs. We show
      that Src64B binds to Dof and that Src kinases contribute to FGFR-dependent MAPK
      activation. Phosphorylation of the novel tyrosine motifs is required for the
      interaction of Dof with Src64B. Thus, Src64B recruitment to Dof through the novel
      phosphosites can provide a new link to MAPK activation and other cellular
      responses. This may give a molecular explanation for the involvement of Src
      kinases in FGF-dependent developmental events.

PMID- 20154140
TI  - The nematode eukaryotic translation initiation factor 4E/G complex works with a
      trans-spliced leader stem-loop to enable efficient translation of
      trimethylguanosine-capped RNAs.
AB  - Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex
      to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G
      mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG)
      cap and a sequence, the SL, to the 5' end of mRNAs. Efficient translation of TMG
      capped mRNAs in nematodes requires the SL sequence. Here we define a core set of
      nucleotides and a stem-loop within the 22-nucleotide nematode SL that stimulate
      translation of mRNAs with a TMG cap. The structure and core nucleotides are
      conserved in other nematode SLs and correspond to regions of SL1 required for
      early Caenorhabditis elegans development. These SL elements do not facilitate
      translation of m(7)G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or
      plant translation systems. Similar stem-loop structures in phylogenetically
      diverse SLs are predicted. We show that the nematode eukaryotic translation
      initiation factor 4E/G (eIF4E/G) complex enables efficient translation of the TMG
      SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is
      determined by eIF4E/G interaction with the cap and the SL RNA, although the SL
      does not increase the affinity of eIF4E/G for capped RNA. These results suggest
      that the mRNA 5' untranslated region (UTR) can play a positive and novel role in
      translation initiation through interaction with the eIF4E/G complex in nematodes
      and raise the issue of whether eIF4E/G-RNA interactions play a role in the
      translation of other eukaryotic mRNAs.

PMID- 20154141
TI  - Alternative chromatin structures of the 35S rRNA genes in Saccharomyces
      cerevisiae provide a molecular basis for the selective recruitment of RNA
      polymerases I and II.
AB  - In all eukaryotes, a specialized enzyme, RNA polymerase I (Pol I), is dedicated
      to transcribe the 35S rRNA gene from a multicopy gene cluster, the ribosomal DNA
      (rDNA). In certain Saccharomyces cerevisiae mutants, 35S rRNA genes can be
      transcribed by RNA polymerase II (Pol II). In these mutants, rDNA silencing of
      Pol II transcription is impaired. It has been speculated that upstream activating
      factor (UAF), which binds to a specific DNA element within the Pol I promoter,
      plays a crucial role in forming chromatin structures responsible for polymerase
      specificity and silencing at the rDNA locus. We therefore performed an in-depth
      analysis of chromatin structure and composition in different mutant backgrounds.
      We demonstrate that chromatin architecture of the entire Pol I-transcribed region
      is substantially altered in the absence of UAF, allowing RNA polymerases II and
      III to access DNA elements flanking a Pol promoter-proximal Reb1 binding site.
      Furthermore, lack of UAF leads to the loss of Sir2 from rDNA, correlating with
      impaired Pol II silencing. This analysis of rDNA chromatin provides a molecular
      basis, explaining many phenotypes observed in previous genetic analyses.

PMID- 20154142
TI  - Notch exhibits ligand bias and maneuvers stage-specific steering of neural
      differentiation in embryonic stem cells.
AB  - Notch dictates multiple developmental events, including stem cell maintenance and
      differentiation, through intercellular communication. However, its temporal
      influence during early development and, of particular interest, its regulation of
      binary fate decision at different stages during neurogenesis are among the least
      explored. Here, using an embryonic stem cell (ESC) model, we have deciphered
      Notch ligand preference during ESC commitment to different germ layers and
      determined the stage-specific temporal effect of Notch during neural
      differentiation. ESCs during maintenance remain impervious to Notch inhibition.
      However, Notch activation promotes differentiation even in the presence of
      leukemia inhibitory factor (LIF), displaying ligand preference-associated lineage
      discrimination, where Jagged-1 favors neural commitment and Delta-like-4 favors
      the mesoderm. This differential ligand action involves a combination of Notch
      receptors influencing specific downstream target gene expression. Though Notch
      activation during early neural differentiation specifically promotes neural stem
      cells or early neural progenitors and delays their maturation, its inhibition
      promotes late neural progenitors and expedites neurogenesis, with a preference
      for neurons over glia. However, gliogenesis is promoted upon Notch activation
      only when executed in combination with ciliary neurotrophic factor. Thus, our
      investigation underscores a multifaceted role of Notch, demonstrating the
      interdependency of ligand usage and lineage specification and Notch acting as a
      master switch, displaying stage-specific influence on neurogenesis.

PMID- 20154143
TI  - Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and
      subsequent degradation.
AB  - Hedgehog (Hh) signaling in vertebrates depends on intraflagellar transport (IFT)
      within primary cilia. The Hh receptor Patched is found in cilia in the absence of
      Hh and is replaced by the signal transducer Smoothened within an hour of Hh
      stimulation. By generating antibodies capable of detecting endogenous pathway
      transcription factors Gli2 and Gli3, we monitored their kinetics of accumulation
      in cilia upon Hh stimulation. Localization occurs within minutes of Hh addition,
      making it the fastest reported readout of pathway activity, which permits more
      precise temporal and spatial localization of Hh signaling events. We show that
      the species of Gli3 that accumulates at cilium tips is full-length and likely not
      protein kinase A phosphorylated. We also confirmed that phosphorylation and
      betaTrCP/Cul1 are required for endogenous Gli3 processing and that this is
      inhibited by Hh. Surprisingly, however, Hh-dependent inhibition of processing
      does not lead to accumulation of full-length Gli3, but instead renders it labile,
      leading to its proteasomal degradation via the SPOP/Cul3 complex. In fact, full
      length Gli3 disappears with faster kinetics than the Gli3 repressor, the latter
      not requiring SPOP/Cul3 or betaTrCP/Cul1. This may contribute to the increased
      Gli3 activator/repressor ratios found in IFT mutants.

PMID- 20154144
TI  - Uncoupling of expression of an intronic microRNA and its myosin host gene by exon
      skipping.
AB  - The ancient MYH7b gene, expressed in striated muscle and brain, encodes a
      sarcomeric myosin and the intronic microRNA miR-499. We find that skipping of an
      exon introduces a premature termination codon in the transcript that
      downregulates MYH7b protein production without affecting microRNA expression.
      Among other genes, endogenous miR-499 targets the 3' untranslated region of the
      transcription factor Sox6, which in turn acts as a repressor of MYH7b
      transcriptional activity. Thus, concerted transcription and alternative splicing
      uncouple the level of expression of MYH7b and miR-499 when their coexpression is
      not required.

PMID- 20154145
TI  - The chaperone-like protein HYPK acts together with NatA in cotranslational N
      terminal acetylation and prevention of Huntingtin aggregation.
AB  - The human NatA protein N(alpha)-terminal-acetyltransferase complex is responsible
      for cotranslational N-terminal acetylation of proteins with Ser, Ala, Thr, Gly,
      and Val N termini. The NatA complex is composed of the catalytic subunit hNaa10p
      (hArd1) and the auxiliary subunit hNaa15p (hNat1/NATH). Using immunoprecipitation
      coupled with mass spectrometry, we identified endogenous HYPK, a Huntingtin (Htt)
      interacting protein, as a novel stable interactor of NatA. HYPK has chaperone
      like properties preventing Htt aggregation. HYPK, hNaa10p, and hNaa15p were
      associated with polysome fractions, indicating a function of HYPK associated with
      the NatA complex during protein translation. Knockdown of both hNAA10 and hNAA15
      decreased HYPK protein levels, possibly indicating that NatA is required for the
      stability of HYPK. The biological importance of HYPK was evident from HYPK
      knockdown HeLa cells displaying apoptosis and cell cycle arrest in the G(0)/G(1)
      phase. Knockdown of HYPK or hNAA10 resulted in increased aggregation of an Htt
      enhanced green fluorescent protein (Htt-EGFP) fusion with expanded polyglutamine
      stretches, suggesting that both HYPK and NatA prevent Htt aggregation.
      Furthermore, we demonstrated that HYPK is required for N-terminal acetylation of
      the known in vivo NatA substrate protein PCNP. Taken together, the data indicate
      that the physical interaction between HYPK and NatA seems to be of functional
      importance both for Htt aggregation and for N-terminal acetylation.

PMID- 20154146
TI  - OGFOD1, a novel modulator of eukaryotic translation initiation factor 2alpha
      phosphorylation and the cellular response to stress.
AB  - Cells possess mechanisms that permit survival and recovery from stress, several
      of which regulate the phosphorylation of eukaryotic translation initiation factor
      2alpha (eIF2alpha). We identified the human OGFOD1 protein as a novel stress
      granule component that regulates the phosphorylation of eIF2alpha and the
      resumption of translation in cells recovering from arsenite-induced stress.
      Coimmunoprecipitation studies revealed that OGFOD1 associates with a small subset
      of stress granule proteins (G3BP1, USP10, Caprin1, and YB-1) and the ribosome in
      both unstressed and stressed cells. Overexpression of OGFOD1 led to increased
      abundance of phosphorylated eIF2alpha, both in unstressed cells and in cells
      exposed to arsenite-induced stress, and to accelerated apoptosis during stress.
      Conversely, knockdown of OGFOD1 resulted in smaller amounts of phosphorylated
      eIF2alpha and a faster accumulation of polyribosomes in cells recovering from
      stress. Finally, OGFOD1 interacted with both eIF2alpha and the eIF2alpha kinase
      heme-regulated inhibitor (HRI), which was identified as a novel stress granule
      resident. These findings argue that OGFOD1 plays important proapoptotic roles in
      the regulation of translation and HRI-mediated phosphorylation of eIF2alpha in
      cells subjected to arsenite-induced stress.

PMID- 20154147
TI  - The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the
      inner and outer membranes.
AB  - Dynamic interactions between components of the outer (OM) and inner (IM)
      membranes control a number of critical mitochondrial functions such as channeling
      of metabolites and coordinated fission and fusion. We identify here the
      mitochondrial AAA(+) ATPase protein ATAD3A specific to multicellular eukaryotes
      as a participant in these interactions. The N-terminal domain interacts with the
      OM. A central transmembrane segment (TMS) anchors the protein in the IM and
      positions the C-terminal AAA(+) ATPase domain in the matrix. Invalidation studies
      in Drosophila and in a human steroidogenic cell line showed that ATAD3A is
      required for normal cell growth and cholesterol channeling at contact sites.
      Using dominant-negative mutants, including a defective ATP-binding mutant and a
      truncated 50-amino-acid N-terminus mutant, we showed that ATAD3A regulates
      dynamic interactions between the mitochondrial OM and IM sensed by the cell
      fission machinery. The capacity of ATAD3A to impact essential mitochondrial
      functions and organization suggests that it possesses unique properties in
      regulating mitochondrial dynamics and cellular functions in multicellular
      organisms.

PMID- 20154148
TI  - Mechanisms of recombination between diverged sequences in wild-type and BLM
      deficient mouse and human cells.
AB  - Double-strand breaks (DSBs) are particularly deleterious DNA lesions for which
      cells have developed multiple mechanisms of repair. One major mechanism of DSB
      repair in mammalian cells is homologous recombination (HR), whereby a homologous
      donor sequence is used as a template for repair. For this reason, HR repair of
      DSBs is also being exploited for gene modification in possible therapeutic
      approaches. HR is sensitive to sequence divergence, such that the cell has
      developed ways to suppress recombination between diverged ("homeologous")
      sequences. In this report, we have examined several aspects of HR between
      homeologous sequences in mouse and human cells. We found that gene conversion
      tracts are similar for mouse and human cells and are generally < or =100 bp, even
      in Msh2(-)(/)(-) cells which fail to suppress homeologous recombination. Gene
      conversion tracts are mostly unidirectional, with no observed mutations.
      Additionally, no alterations were observed in the donor sequences. While both
      mouse and human cells suppress homeologous recombination, the suppression is
      substantially less in the transformed human cells, despite similarities in the
      gene conversion tracts. BLM-deficient mouse and human cells suppress homeologous
      recombination to a similar extent as wild-type cells, unlike Sgs1-deficient
      Saccharomyces cerevisiae.

PMID- 20154149
TI  - Cadherins and Pak1 control contact inhibition of proliferation by Pak1-betaPIX
      GIT complex-dependent regulation of cell-matrix signaling.
AB  - It is crucial for organ homeostasis that epithelia have effective mechanisms to
      restrict motility and cell proliferation in order to maintain tissue
      architecture. On the other hand, epithelial cells need to rapidly and transiently
      acquire a more mesenchymal phenotype, with high levels of cell motility and
      proliferation, in order to repair epithelia upon injury. Cross talk between cell
      cell and cell-matrix signaling is crucial for regulating these transitions. The
      Pak1-betaPIX-GIT complex is an effector complex downstream of the small GTPase
      Rac1. We previously showed that translocation of this complex from cell-matrix to
      cell-cell adhesion sites was required for the establishment of contact inhibition
      of proliferation. In this study, we provide evidence that this translocation
      depends on cadherin function. Cadherins do not recruit the complex by direct
      interaction. Rather, we found that inhibition of the normal function of cadherin
      or Pak1 leads to defects in focal adhesion turnover and to increased signaling by
      phosphatidylinositol 3-kinase. We propose that cadherins are involved in
      regulation of contact inhibition by controlling the function of the Pak1-betaPIX
      GIT complex at focal contacts.

PMID- 20154150
TI  - HSP70 and its cochaperone CPIP promote potyvirus infection in Nicotiana
      benthamiana by regulating viral coat protein functions.
AB  - This study demonstrates that heat shock protein 70 (HSP70) together with its
      cochaperone CPIP regulates the function of a potyviral coat protein (CP), which
      in turn can interfere with viral gene expression. HSP70 was copurified as a
      component of a membrane-associated viral ribonucleoprotein complex from Potato
      virus A-infected plants. Downregulation of HSP70 caused a CP-mediated defect
      associated with replication. When PVA CP was expressed in trans, it interfered
      with viral gene expression and replication-associated translation (RAT). However,
      CP produced in cis interfered specifically with RAT. CPIP binds to potyviral CP,
      and overexpression of CPIP was sufficient to restore RAT inhibited by expression
      of CP in trans. Restoration of RAT was dependent on the ability of CPIP to
      interact with HSP70 since expression of a J-domain mutant, CPIP(Delta66), had
      only a minor effect on RAT. CPIP-mediated delivery of CP to HSP70 promoted CP
      degradation by increasing its ubiquitination when assayed in the absence of virus
      infection. In conclusion, CPIP and HSP70 are crucial components of a distinct
      translation activity that is associated with potyvirus replication.

PMID- 20154151
TI  - The central element protein ZEP1 of the synaptonemal complex regulates the number
      of crossovers during meiosis in rice.
AB  - ZEP1, a transverse filament (TF) protein, is the rice (Oryza sativa) homolog of
      Arabidopsis thaliana ZYP1. In the Tos17-insertional zep1 mutants, homologous
      chromosomes align along the entire length of the chromosome, but the synaptonemal
      complex is not assembled in early prophase I. Crossovers are well formed, and 12
      bivalents could be detected from diakinesis to metaphase I, which leads to equal
      chromosomal segregation in anaphase I. Moreover, the number of crossovers has a
      tendency to be increased compared with that in the wild type. These phenomena are
      different from the TF mutants identified so far in other organisms. Chiasma
      terminalization of the bivalent, which occurs frequently in the wild type, seldom
      occurred in zep1. Transmission electron micrographs and immunodetection using an
      antibody against ZEP1 showed that ZEP1 is the central element of the synaptonemal
      complex. Although PAIR2 and MER3 were loaded normally in zep1, their dissociation
      was delayed severely compared with the wild type. In addition, ZEP1 is reloaded
      onto chromosomes in early microspores as the chromosome decondense, suggesting
      that ZEP1 might have other biological functions during this process.

PMID- 20154152
TI  - The Arabidopsis thaliana STYLISH1 protein acts as a transcriptional activator
      regulating auxin biosynthesis.
AB  - The establishment and maintenance of auxin maxima in vascular plants is regulated
      by auxin biosynthesis and polar intercellular auxin flow. The disruption of
      normal auxin biosynthesis in mouse-ear cress (Arabidopsis thaliana) leads to
      severe abnormalities, suggesting that spatiotemporal regulation of auxin
      biosynthesis is fundamental for normal growth and development. We have shown
      previously that the induction of the SHORT-INTERNODES/STYLISH (SHI/STY) family
      member STY1 results in increased transcript levels of the YUCCA (YUC) family
      member YUC4 and also higher auxin levels and auxin biosynthesis rates in
      Arabidopsis seedlings. We have also shown previously that SHI/STY family members
      redundantly affect development of flowers and leaves. Here, we further examine
      the function of STY1 by analyzing its DNA and protein binding properties. Our
      results suggest that STY1, and most likely other SHI/STY members, are DNA binding
      transcriptional activators that target genes encoding proteins mediating auxin
      biosynthesis. This suggests that the SHI/STY family members are essential
      regulators of auxin-mediated leaf and flower development. Furthermore, the lack
      of a shoot apical meristem in seedlings carrying a fusion construct between STY1
      and a repressor domain, SRDX, suggests that STY1, and other SHI/STY members, has
      a role in the formation and/or maintenance of the shoot apical meristem, possibly
      by regulating auxin levels in the embryo.

PMID- 20154153
TI  - Factors influencing the differentiation of bovine preadipocytes in vitro.
AB  - Our objectives were to isolate bovine stromal-vascular cells using explants and
      to determine media components that promote differentiation into mature adipocytes
      for studies of lipogenic enzyme regulation. Stromal-vascular cells were grown
      from explants and treated with differentiation media for 8 d after reaching
      confluence. Differentiation was assessed by measuring radiolabeled acetate
      incorporation into lipids, glycerol-3-phosphate dehydrogenase activity, and the
      mRNA expression of fatty acid binding protein-4, PPAR-gamma, and acetyl-CoA
      carboxylase-alpha (ACCalpha). After 8 d of differentiation, medium containing 10
      microg/mL of insulin, 0.25 microM dexamethasone, 0.5 mM isobutylmethylxanthine, 1
      mM octanoate, and 2% Intralipid (Fisher Scientific, Suwanee, GA) produced greater
      acetate incorporation (P < 0.001) and glycerol-3-phosphate dehydrogenase activity
      (P < 0.001) compared with other media tested. This differentiation medium also
      increased mRNA expression of fatty acid binding protein-4, PPARgamma, and
      ACCalpha by 180-, 7-, and 3-fold, respectively, compared with undifferentiated
      control cells (P < 0.05). To further improve the differentiation protocol, the
      effects of Intralipid, rosiglitazone, and troglitazone were examined. Removal of
      2% Intralipid did not improve any differentiation measures. Addition of
      rosiglitazone (1 microM), a PPAR-gamma agonist, increased acetate incorporation
      and ACCalpha mRNA (P < 0.01). Addition of troglitazone (5 microM), another PPAR
      gamma agonist, increased acetate incorporation to a similar extent as
      rosiglitazone and produced the greatest expression of ACCalpha mRNA (P < 0.01),
      but was not superior to medium that included rosiglitazone for any other
      differentiation measures. Cell-seeding density influences the cell divisions
      required to reach confluence, and increased plating density (2 x 10(4)
      cells/cm(2) vs. 6.7 x 10(3) cells/cm(2)) increased acetate incorporation by 100%
      (P < 0.001). Differentiating stromal-vascular cells in the presence of trans-10,
      cis-12 CLA inhibited differentiation of stromal-vascular cells into mature
      adipocytes, reducing radiolabeled acetate incorporation into lipids (P < 0.001),
      stearoyl-CoA desaturase-1 mRNA (P < 0.05) and protein abundance (P < 0.05), and
      ACCalpha protein abundance (P < 0.05). We have developed a method to
      differentiate primary bovine adipocytes, which will allow us to study the
      regulation of lipogenic enzymes by nutrient and endocrine factors.

PMID- 20154154
TI  - Induction of peroxisomal proliferator-activated receptor gamma and peroxisomal
      proliferator-activated receptor gamma coactivator 1 by unsaturated fatty acids,
      retinoic acid, and carotenoids in preadipocytes obtained from bovine white
      adipose tissue1,2.
AB  - The importance of dietary fat components, such as fatty acids, in the expression
      of multiple genes is clear. In the case of beef cattle, fat in the form of fatty
      acids (saturated or unsaturated), vitamin A (mainly retinoic acid), or
      carotenoids (beta-carotene and lutein) is obtained from dietary feed or pasture.
      The aim of this work was to study the effect of fatty acids (phytanic and
      pristanic acids), vitamin A (all-trans and 9-cis retinoic acid), and carotenoids
      (beta-carotene and lutein) on the expression of PPARgamma and its coactivator PGC
      1alpha during differentiation of bovine white adipose tissue. Samples were
      collected at slaughter from subcutaneous adipose tissue and processed in a
      solution containing type II collagenase for 2 h at 37 degrees C. Cells were
      resuspended in basal medium, Dulbecco's modified Eagle's medium containing 5%
      fetal bovine serum, plated on 24-well culture plates at a density of 1 x 10(4)
      cells/cm(2), and incubated at 37 degrees C in a 5% CO(2) atmosphere. Preadipocyte
      differentiation after reaching confluence was induced by various treatments:
      rosiglitazone (20 microM); unsaturated fatty acids: phytanic acid (25, 50, 100
      microM) and pristanic acid (25, 50, 100 microM); retinoids: 9-cis retinoic acid
      (0.5, 0.75, 1 microM) and all-trans retinoic acid (0.5, 0.75, 1 microM); and
      carotenoids: beta-carotene (10, 20, 30 microM) and lutein (10, 20, 30 microM).
      Expression of PPARgamma and PGC-1alpha was measured in differentiated cells.
      Phytanic acid, all-trans retinoic acid, and 9-cis retinoic acid were the best
      activators of PPARgamma expression, and the combination of 9-cis and all-trans
      retinoic acid was the best activator of PGC-1alpha expression (P < 0.05).
      Therefore, these are powerful agents for the promotion of bovine adipogenesis and
      constitute promising compounds to be used in bovine fattening.

PMID- 20154155
TI  - Fatty acid profile of colostrum and milk of ewes supplemented with fish meal and
      the subsequent plasma fatty acid status of their lambs.
AB  - The objectives of the current study were to 1) determine whether a fish-meal
      supplemented diet fed to ewes during late gestation and early lactation would
      increase the proportion of docosahexaenoic acid (22:6n-3) in colostrum and milk
      and 2) examine the subsequent effect on the plasma fatty acid profile of nursing
      lambs. Eight gestating ewes (Rideau-Arcott; 97 +/- 5 kg of initial BW; 100 d of
      gestation) were used in a completely randomized design. Ewes were individually
      housed and fed a control diet (supplemented with soybean meal) or a fish-meal
      supplemented diet for 6 wk before lambing and throughout 7 wk of lactation.
      Colostrum at d 0 and milk samples at d 36 and 49 of lactation were collected.
      Blood samples were collected from lambs throughout the preweaning period (at 0,
      36, and 49 d of age). Fatty acids of the samples were analyzed by GLC. The ewes
      fed the fish-meal-supplemented diet had greater (P <or= 0.013) percentages (g/100
      g of total fatty acids) of eicosapentaenoic acid (20:5n-3, 0.16 vs. 0.08),
      docosahexaenoic acid (0.33 vs. 0.09), total n-3-PUFA (2.72 vs. 1.91), total CLA
      (0.83 vs. 0.64), and total very long chain n-3-PUFA (>C18, 0.70 vs. 0.38), in
      colostrum and milk compared with the ewes fed the control diet. However, these
      fatty acids, excluding total n-3-PUFA, did not change over time, nor was there an
      interaction between diet and time. The percentage of total SFA was increased (P =
      0.012) linearly over time without having any diet effect. The ratio of n-6-PUFA
      to n-3-PUFA in colostrum and milk from the control group was greater (P = 0.003)
      than that of the fish-meal-supplemented group. This ratio was decreased over time
      (P = 0.001). At birth (d 0), lambs born to the fish-meal-supplemented ewes had
      greater (P = 0.001) plasma concentrations (g/100 g of total fatty acids) of
      eicosapentaenoic acid, docosahexaenoic acid, and total very long chain n-3-PUFA
      than the lambs born to the control ewes. The concentrations of these fatty acids
      were further increased over time (P = 0.001) for the lambs nursing ewes fed the
      fish-meal-supplemented diet. The present findings suggest that the concentrations
      of docosahexaenoic acid in ewe colostrum and milk can be enhanced through diet
      supplementation with fish meal. The docosahexaenoic acid status of their suckling
      lambs can also be further enhanced, and this may contribute to improve neural
      tissue development and overall performance of suckling lambs.

PMID- 20154156
TI  - Using alfalfa leaf meal as a supplement in late-gestation beef heifer and nursing
      beef calf diets.
AB  - Two experiments were conducted to investigate using alfalfa leaf meal (ALM; 22%
      CP, DM basis) in beef cattle diets. In Exp. 1, a total of 24 late-gestation Angus
      heifers (initial BW 470 +/- 9 kg) were blocked by BW, calving date, and BCS to 1
      of 4 dietary treatments in a randomized complete block design. All heifers were
      offered a basal hay diet (7.4% CP and 67.6% NDF, DM basis). Treatments were
      arranged as a 2 x 2 factorial consisting of CP supplied at 100 or 112.5% of the
      recommended daily intake using either soybean meal (SBM) or ALM as the
      supplemental protein source. Treatments were fed for an average of 100 d before
      calving. Total DMI was unaffected by supplemental protein source, although
      heifers consumed more (P < 0.001) ALM supplement than SBM supplement at the
      expense of hay and corn. Feeding 112.5% of recommended CP to heifers increased
      precalving rate of BW gain (P = 0.004) and DM digestibility (P = 0.003). Protein
      source did not affect DM digestibility (P = 0.17). Neither supplemental protein
      source nor protein amount affected changes in BCS or calving traits. In Exp. 2,
      replicates of treatments were conducted over 2 consecutive years at 2 locations
      in northern Minnesota to determine the effects of including ALM in creep-fed
      supplements on nursing calf performance, supplement BW gain efficiency (GF; BW
      gain over control/supplement intake), and cow performance. Treatments were
      control (no supplement), ALM supplement (58% ALM, as-fed basis), or a wheat
      middling- and soybean hull-based supplement (MIDD). Milk intake (estimated by the
      weigh-suckle-weigh technique) was similar among treatments. Creep-fed calves had
      greater (P < 0.001) ADG than control calves, whereas calves offered MIDD tended
      to have greater ADG (P = 0.05) than those offered ALM (1.38 vs. 1.30 kg/d,
      respectively). Calves offered MIDD had greater (P < 0.001) creep feed DMI than
      those offered ALM (2.6 vs. 1.3 kg/d, respectively). A year x treatment
      interaction was noted for GF (P = 0.02). In yr 1, GF for calves offered ALM was
      greater (P = 0.006) than GF for calves offered MIDD, but in yr 2, there were no
      differences. Alfalfa leaf meal may substitute for SBM in beef heifer wintering
      diets and conventional creep feed ingredients. When included in creep feed diets,
      ALM can result in slightly less ADG and less DMI, but supplement conversion
      efficiency may be increased.

PMID- 20154157
TI  - Growth characteristics, reproductive performance, and evaluation of their
      associative relationships in Brangus cattle managed in a Chihuahuan Desert
      production system1.
AB  - Balancing growth and reproductive performance in beef cattle managed in desert
      environments is challenging. Our objectives were to 1) evaluate trends in growth
      and reproductive traits, and 2) assess associative relationships between growth
      characteristics and reproductive performance in a Brangus herd managed in a
      Chihuahuan Desert production system from 1972 to 2006. Data were from bull (n =
      597) and heifer calves (n = 585; 1988 to 2006) and cows (n = 525; repeated
      records of cows, n = 2,611; 1972 to 2006). Variables describing the growth curve
      of each cow were estimated using a nonlinear logistic function (each cow needed 6
      yr of data). Mixed-effect models and logistic regression were used to analyze
      trends across years in growth and reproductive traits (both continuous and
      categorical). For continuous traits of calves, a slight cubic response (P < 0.01)
      described the dynamics of birth weight, 205-d BW, and 365-d BW across years. For
      categorical traits of females, positive linear trends (P < 0.05) across years
      were observed in percent pregnant as yearlings, calved at 2 yr of age, and first
      calf heifer rebreeding (slopes ranged from 0.007 to 0.014%/yr). Autumn cow BW
      increased gradually until 1997 (509 kg +/- 8.8) and then decreased gradually by
      0.6 kg/yr, whereas pregnancy percentage decreased gradually until 1995 (78.4% +/-
      1.0) and then increased slightly by 0.2%/yr. A quadratic effect best described
      the dynamics of these 2 variables across years (P < 0.01) as well as estimates
      describing the growth curve of each cow. Specifically, asymptotic BW and age
      increased (P < 0.05) from 1972 to 1983 and 1990, respectively. Asymptotic age
      then decreased by 27% from 1983 to 1996 (P < 0.05). The maturing rate index was
      negatively correlated with age at first calving and calving interval (r = -0.42
      and -0.18, P < 0.01), which suggested that early-maturing cows had enhanced
      fertility in this environment and production system. In summary, minimal changes
      were observed in measures of growth in bulls and heifers in a Brangus herd
      managed in the Chihuahuan Desert. Opposing relationships were observed among
      measures of cow size and fertility; as growth curves shifted toward earlier
      maturity, measures of reproductive performance suggested that fertility improved.

PMID- 20154158
TI  - Effect of supplemental ground flaxseed fed to beef cattle grazing summer native
      range on the northern Great Plains.
AB  - Two experiments were conducted simultaneously to evaluate the effects of
      supplemental ground flaxseed on site and extent of digestion and growth
      performance in beef cattle grazing summer native range. Six Angus heifers
      (initial BW 367 +/- 8.0 kg) fitted with ruminal and duodenal cannulas were used
      in Exp. 1, and 18 Angus cross steers (initial BW 368 +/- 4.6 kg) were used in
      Exp. 2. Cattle from both experiments were allotted to 1 of 3 individually fed
      treatments: grazing only (CON), grazing plus a cracked corn-soybean meal
      supplement fed at 0.32% of BW once daily (CRN), or grazing plus ground flaxseed
      fed at 0.18% of BW once daily (FLX). In Exp. 1, supplement did not affect (P =
      0.24) masticate in vitro OM digestibility; however, between supplemented
      treatments, cattle fed FLX tended (P = 0.10) to select a lesser quality masticate
      than corn-fed cattle. Forage OM intake was not affected (P = 0.17) by
      supplementation, nor was there a difference (P = 0.51) between CRN and FLX. A
      quadratic (P = 0.001) response was observed for forage OM intake as the grazing
      season advanced. Duodenal and fecal OM flows were not different (P >or= 0.42)
      across treatments. Therefore, true ruminal and total tract OM digestibilities did
      not differ (P >or= 0.40) between CON and supplement treatments, and total tract
      digestibility was greater (P = 0.04) for CRN than FLX. Total duodenal N flow did
      not differ (P = 0.20) across treatments, but responded quadratically (P = 0.03)
      with advancing season. True ruminal N digestibility was not affected by
      supplementation (P >or= 0.20). Likewise, ruminal NDF digestibility did not differ
      (P = 0.29) with supplementation, and CRN was not different (P = 0.27) from FLX.
      In Exp. 2, there was a treatment x period interaction for forage intake (P <
      0.001), ADG (P = 0.001), and feed efficiency (P < 0.001). Supplement did not
      change (P = 0.34) forage intake compared with CON, but it was greater for CRN
      than FLX (P < 0.001). Nevertheless, ADG was greater for supplemented steers (P <
      0.001) compared with CON, but did not differ (P = 0.41) between CRN and FLX. Feed
      efficiency was improved (P < 0.001) for supplemented steers and was greater (P =
      0.01) for FLX than CRN. Although ground flaxseed reduced digestibility compared
      with a corn-soybean supplement, this reduction in diet digestibility did not
      negatively affect the growth performance of grazing steers.

PMID- 20154159
TI  - Modeling the relationship between scanned rump and 12th-rib fat in young
      temperate and tropical bovines: model development and evaluation.
AB  - A decision support tool for predicting subcutaneous fat depths called BeefSpecs,
      based on the Davis growth model (DGM), has been developed by the Cooperative
      Research Centre for Beef Genetic Technologies. Currently, the DGM predicts 12th
      rib fat thickness (RFT, mm). To allow predictions of fat thickness at the P8 rump
      (P8FT, mm) site, the standard carcass fat measurement in the Australian beef
      industry, a relationship was developed between ultrasound RFT and P8FT in steers
      and heifers from temperate (Angus, Hereford, Shorthorn, and Murray Grey) and
      tropical (Brahman, Belmont Red, and Santa Gertrudis) breed types. Model
      development involved fitting various combinations of sex, breed type (BrT), BW,
      age, and RFT to produce 6 models. The models were challenged with data from 3
      independent data sets: 1) Angus steers from 2.4 generations of divergent
      selection for and against residual feed intake; 2) 2 tropically adapted genotypes
      [Brahman and tropically adapted composites (combinations of Belmont Red,
      Charbray, Santa Gertrudis, Senepol, and Brahman breeds)]; and 3) a study using
      sires from Charolais, Limousin, Belgian Blue, and Black and Red Wagyu breeds and
      3 genetic lines of Angus to create divergence in progeny in terms of genetic
      potential for intramuscular fat percent and retail beef yield. When challenged
      with data from Angus cattle, the mean biases (MB, mm) for models A to F were 
      1.23, -0.56, -0.56, -0.02, 0.14, and 0.04, and the root mean square errors of
      predictions (mm) were 1.53, 0.97, 0.97, 0.92, 0.93, and 0.91, respectively. When
      challenged with data from Brahman cattle, MB were 0.04, -0.22, -0.14, 0.05, 
      0.11, and 0.02 and root mean square errors of predictions were 1.30, 1.29, 1.27,
      1.23, 1.37, and 1.29, respectively. Generally, model accuracy indicated by MB
      tended to be less for model E, which contained age rather than BW as a covariate.
      Models B and C were generally robust when challenged with data from Angus,
      Brahman, and Tropical Composite cattle as well as crossbred cattle with temperate
      sires. Model D, which did not contain age, performed the most consistently and
      was selected for inclusion in the DGM: P8FT, mm = -3.6 (+/-0.14) + 1.3 (+/-0.13)
      x sex + 0.11 (+/-0.13) x BrT + 0.014 (+/-4.8E(-4)) x BW + 0.96 (+/-0.01) x RFT -
      0.73 (+/-0.08) x sex x BrT - 3.8E(-3) (+/-4.2E(-4)) x sex x BW - 0.09 (+/-0.01) x
      sex x RFT + 1.3E(-3) (+/-3.7E(-4)) x BrT x BW + 0.24 (+/-0.01) x BrT x RFT
      (adjusted R(2) = 0.86; SE = 0.013). Model D has been implemented in BeefSpecs to
      predict P8FT.

PMID- 20154160
TI  - Effects of exposure to calves persistently infected with bovine viral diarrhea
      virus type 1b and Mannheimia haemolytica challenge on animal performance,
      nitrogen balance, and visceral organ mass in beef steers.
AB  - Bovine viral diarrhea viruses (BVDV) have been isolated alone or in combination
      with other viral and bacterial pathogens in animals diagnosed with bovine
      respiratory disease (BRD), a disease causing major economic loss to the feedlot
      industry. The objective of this experiment was to determine the effects of
      Mannheimia haemolytica challenge after short-term exposure (72 h) to bovine viral
      diarrhea virus type 1b (BVDV1b) persistently infected (PI) calves on performance,
      N balance, and organ mass in finishing cattle. Treatments (6 steers/treatment;
      initial BW = 314 +/- 31 kg) were 1) steers not exposed to steers PI with BVDV nor
      challenged with M. haemolytica (control; CON); 2) steers exposed to 2 steers PI
      with BVDV1b (BVD) for 72 h; 3) steers intratracheally challenged with M.
      haemolytica (MH); or 4) steers exposed to 2 steers PI with BVDV1b for 72 h and
      challenged with M. haemolytica (BVD+MH). There were 12 h between exposure to PI
      steers and challenge with M. haemolytica. Steers were housed in metabolism
      stanchions during the first 5 d after the M. haemolytica challenge and on d 7 to
      11, 28 to 32, and for 5 d before slaughter (average 119 d on feed) to determine N
      balance and were weighed every 28 d. At slaughter, carcass and organ mass data
      were collected. Data were analyzed as a randomized complete block design with a 2
      x 2 factorial arrangement of treatments, and steer was used as the experimental
      unit. From d -3 (beginning of PI steer exposure) to 4, steers challenged with M.
      haemolytica had less (P = 0.04) ADG than steers not challenged with M.
      haemolytica. In addition, steers exposed to steers PI with BVDV tended (P = 0.09)
      to have less ADG and G:F across the entire finishing period than steers not
      exposed to BVDV. Before slaughter, retained N expressed as grams per day (P =
      0.03) and as a percentage of N intake (P = 0.04) was less in BVD steers compared
      with steers not exposed to BVDV. There were no effects (P > 0.10) of BVDV
      exposure or M. haemolytica challenge on empty BW (EBW) or carcass
      characteristics. Expressed as a percentage of EBW, HCW was less (P = 0.02) and
      total offal weight was greater (P = 0.02) for steers challenged with M.
      haemolytica compared with steers not challenged. Results are in agreement with
      those reported in larger scale finishing studies and suggest that acute exposure
      to BRD-related pathogens can have long-term effects on animal performance.

PMID- 20154161
TI  - The nutritional value of expeller-pressed canola meal for grower-finisher pigs.
AB  - Expeller-pressed (EP) canola meal contains more residual oil than solvent
      extracted canola meal and might be an attractive feedstuff for swine, but it has
      been poorly characterized. In Exp. 1, six ileal-cannulated barrows (36 kg of BW)
      were fed at 3x maintenance either a 44% EP canola meal diet or a N-free diet in a
      crossover design to measure energy and AA digestibility and calculate
      standardized ileal digestible (SID) AA and NE content, with 6 observations per
      diet. Each period consisted of a 5-d diet adaptation and a 2-d feces and 3-d
      digesta collection. The EP canola meal contained (% of DM) 38.5% CP, 13.3% ether
      extract, 2.42% Lys, 1.54% Thr, 0.62% Met, and 23.2 micromol/g of glucosinolates.
      Apparent total tract energy digestibility was 75.0% and the DE and predicted NE
      content were 3.77 and 2.55 Mcal/kg (in DM), respectively. The SID AA content (%
      of DM) was 1.77% Lys, 1.04% Thr, and 0.52% Met. In Exp. 2, a total of 1,100 pigs
      (25 kg of BW) housed in 50 pens were fed 5 dietary regimens with 0, 7.5, 15, and
      22.5% or decreasing amounts (22.5, 15, 7.5, and 0%, respectively) of EP canola
      meal over 4 phases to validate performance and carcass characteristics. Diets
      were formulated to contain equal NE:SID Lys for each growth phase (g/Mcal; 4.04,
      d 0 to 25; 3.63, d 26 to 50; 3.23, d 51 to 77; 2.83, d 78 to 90). At slaughter,
      carcass characteristics were measured for all pigs, and jowl fat was sampled for
      2 pigs per pen. For d 51 to 90, the 22.5% EP canola meal regimen was reduced to
      18% (22.5/18%) because of decreased ADFI in phases 1 and 2. Overall (d 0 to 90),
      increasing dietary EP canola meal linearly decreased (P < 0.001) ADG and ADFI and
      linearly increased (P < 0.01) G:F. For 0 and 22.5/18% EP canola meal,
      respectively, ADG was 978 and 931 g/d, ADFI was 2.77 and 2.58 kg/d, and G:F was
      0.366 and 0.378. Increasing dietary EP canola meal did not alter the carcass
      backfat thickness, loin depth, or jowl fat fatty acid profile. Pigs fed 22.5/18%
      EP canola meal reached slaughter weight 3 d after (P < 0.05) pigs fed 0% EP
      canola meal. In summary, EP canola meal provided adequate energy and AA; however,
      ADG was reduced by 3 g/d per 1% of EP canola meal inclusion, likely because of
      increased dietary glucosinolates. Thus, the amount of EP canola meal included in
      swine diets should be targeted to an expected growth performance and carcass
      quality. Finally, diets formulated to contain an equal NE and SID AA content did
      not entirely eliminate the risks for reduced growth performance associated with
      inclusion of an alternative feedstuff.

PMID- 20154162
TI  - Energy utilization in pigs selected for high and low residual feed intake.
AB  - Genetic selection on residual feed intake (RFI) can be used as an alternative
      method to G:F to improve feed efficiency in pigs. The objective of this study was
      to determine the effects of selection for RFI on digestive and metabolic
      utilization of energy in 2 lines of purebred French Large White castrated male
      pigs obtained from a divergent selection experiment over 6 generations. The
      RFI(+) (high RFI) line consumed more feed than predicted from performance
      compared with the RFI(-) (low RFI) line. Digestibility of energy and nutrients,
      total heat production (HP), HP related to physical activity, and energy and N
      balance were measured in respiration chambers for a 6-d period in pigs offered
      feed ad libitum. Pigs remained in the chamber for an additional day and did not
      receive any feed to estimate the fasting HP and calculate the thermic effect of
      feeding. Five pairs of 2 littermates from the same farrowing batch were used in
      each line. Because 2 respiration chambers were available for the trial, pigs were
      measured regularly during the 25- to 95-kg growing period. Two pigs per chamber
      were used until pigs reached 45 kg of BW, and 1 pig per chamber was used
      thereafter. Individual feed intake and BW gain were measured continuously from
      weaning to the end of the trial. Pigs were fed 3 diets with decreasing CP
      contents during the 25 to 45 (period 1), 45 to 65 (period 2), and 65 to 95
      (period 3) kg of BW periods. Average daily feed intake was greater in RFI(+) pigs
      than in RFI(-) pigs between 25 and 65 kg of BW (2,128 vs. 1,891 g/d; P < 0.01)
      and G:F was 8% greater in RFI(-) pigs compared with RFI(+) pigs (P < 0.01). There
      was no line effect on digestibility coefficients or N retention, irrespective of
      the experimental period studied. Nitrogen retention was 31.2, 28.7, and 20.8 g/d
      at periods 1, 2, and 3, respectively (P < 0.001). The HP was greater in RFI(+)
      pigs than in RFI(-) pigs (1,497 vs. 1,383 kJ.kg of BW(-0.60).d(-1); P < 0.01),
      with no subsequent line effect on energy retention. The activity-related HP
      tended to be greater in RFI(+) pigs than in RFI(-) pigs (250 vs. 218 kJ.kg of BW(
      0.60).d(-1); P = 0.09), and the fasting HP was 10% greater (P = 0.04) in RFI(+)
      pigs than in RFI(-) pigs (846 vs. 771 kJ.kg of BW(-0.60).d(-1)). The thermic
      effect of feeding, expressed as a percentage of ME intake, was the same for both
      lines of pigs (average, 14.7%). In conclusion, the RFI(+) pigs are energetically
      less efficient because of their greater HP related to physical activity and basal
      metabolic rate.

PMID- 20154163
TI  - Digestibility and nutrient retention of perennial peanut and bermudagrass hays
      for mature horses.
AB  - Mature horses were used to determine apparent DM, OM, NDF, and CP digestibility
      values of 2 bermudagrass (BG; Cynodon dactylon) hays, Coastal (CB) and Tifton 85
      (T85), and Florigraze perennial peanut (PP; Arachis glabrata) hay. In addition,
      N, Ca, and P balances were determined in horses fed those hays. Five mature
      Thoroughbred geldings and 1 Quarter Horse gelding (mean initial BW = 542 +/- 37
      kg) were used (5 horses for the last period) in a 3 x 3 repeated Latin square
      design, with 2 horses per hay and 3 adjustment and collection periods. Horses
      were randomly assigned to pairs and the initial hay to be fed. Each period
      consisted of a 10-d adjustment phase, followed by a 4-d total fecal and urine
      collection phase. Horses were fed at 1.5 (period 1), 1.7 (period 2), or 2%
      (period 3) of their BW daily (DM basis). The 2 BG were grown under similar
      conditions, with CB and T85 being cut at 4 and 5 wk of regrowth, respectively,
      and PP being of a late first cutting. The compositions (DM basis) of PP, CB, and
      T85, respectively, were 93, 94, and 93% DM; 92, 94, and 94% OM; 46, 73, and 77%
      NDF; 34, 37, and 42% ADF; 11, 10, and 8% CP; 1.10, 0.28, 0.27% Ca; and 0.19,
      0.15, and 0.19% P, respectively. Least squares means (pooled SE) for apparent
      digestibility of PP, CB, and T85, respectively, were 65, 53, and 52% (1) DM
      digestibility; 67, 53, and 52% (1) OM digestibility; 44, 50, and 46% (4) NDF
      digestibility; and 66, 60, and 57% (1) CP digestibility. Digestibility values of
      DM and OM were greater (P < 0.001) for PP than for the BG. Digestibility of CP
      was greater (P = 0.001) for PP than for CB or T85, with no difference (P = 0.37)
      between PP and BG hays in NDF digestibility. There were no differences between CB
      and T85 for DM digestibility (P = 0.67), OM digestibility (P = 0.59), CP
      digestibility (P = 0.11), and NDF digestibility (P = 0.48). Nitrogen (P = 0.01)
      and P balances (P = 0.04) were greater for PP than BG hays, whereas N balance of
      CB was greater (P = 0.01) than that of T85. There were no differences among all
      hays in Ca balance (P = 0.54) and between the BG in P balance (P = 0.34). Results
      indicated that PP, CB, and T85 are suitable forages for horses.

PMID- 20154164
TI  - Effects of exposure to calves persistently infected with bovine viral diarrhea
      virus type 1b and subsequent infection with Mannheima haemolytica on clinical
      signs and immune variables: model for bovine respiratory disease via viral and
      bacterial interaction.
AB  - The objective was to determine effects of an intratracheal Mannheimia haemolytica
      challenge after 72-h exposure to bovine viral diarrhea virus type 1b (BVDV1b)
      persistently infected (PI) calves on serum antibody production, white blood cell
      count (WBC), cytokine concentrations, and blood gases in feedlot steers. Twenty
      four steers (initial BW = 314 +/- 31 kg) were randomly allocated to 1 of 4
      treatments (6 steers/treatment) arranged as a 2 x 2 factorial. Treatments were 1)
      steers not exposed to steers PI with BVDV nor challenged with M. haemolytica
      (control; CON); 2) steers exposed to 2 steers PI with BVDV for 72 h (BVD); 3)
      steers intratracheally challenged with M. haemolytica (MH); and 4) steers exposed
      to 2 steers PI with BVDV for 72 h and challenged with M. haemolytica (BVD+MH).
      There were 12 h between exposure to PI steers and challenge with M. haemolytica.
      Rectal temperature was increased (P < 0.001) for MH and BVD+MH during the initial
      24 h after the M. haemolytica challenge. For MH and BVD+MH, total WBC count was
      increased (P < 0.01) at 36 h post M. haemolytica challenge compared with CON,
      whereas in BVD steers, WBC count was decreased (P < 0.01). Total lymphocyte count
      was increased (P = 0.004) during the initial 72 h post BVDV exposure for the BVD
      and BVD+MH groups compared with MH and CON, and this difference remained at 96 h
      post M. haemolytica challenge. An increased (P < 0.001) total neutrophil count
      was observed during the initial 36 h for the MH group and at 72 h for the BVD+MH
      challenge group. Interleukin 1beta, IL-6, and tumor necrosis factor alpha
      (TNFalpha) concentrations were greater (P <or= 0.04) in BVD steers than steers
      not exposed to BVDV, and interferon gamma, IL-1beta, and TNFalpha were greater (P
      <or= 0.02) in MH steers than in steers not challenged with M. haemolytica. There
      were BVD x MH interactions (P <or= 0.04) for plasma carbon dioxide, carbonic
      acid, and sodium bicarbonate concentrations. Challenge with M. haemolytica
      decreased carbon dioxide, carbonic acid, and sodium bicarbonate concentrations to
      a greater extent when steers were not exposed to PI steers compared with steers
      exposed to BVDV. We conclude that the challenge model was successful at inducing
      bovine respiratory disease (BRD) associated with BVDV and M. haemolytica.
      Understanding the physiological changes in morbid animals will lead to improved
      strategies for decreasing severity and economic losses associated with BRD.

PMID- 20154165
TI  - Effects of crude glycerin on performance and carcass characteristics of finishing
      wether lambs.
AB  - The objective of this study was to evaluate the effects of crude glycerin on
      performance and carcass characteristics in finishing wether lambs. Thirty black
      faced, Suffolk-cross wether lambs (44.1 +/- 5.6 kg initial BW) were stratified
      and blocked by BW to 1 of 5 individually fed, isocaloric, isonitrogenous dietary
      treatments containing 0, 5, 10, 15, or 20% crude glycerin (88% pure) on a DM
      basis. Diets were fed once daily for ad libitum consumption and contained 15%
      chopped hay, approximately 25% dried distillers grains with solubles, and the
      specified treatment combination of cracked corn replaced with increasing amounts
      of crude glycerin. Wethers were weighed on 14-d intervals and were selected for
      slaughter when they reached an approximate 12th-rib fat depth of 0.51 cm (28 to
      84 d on trial). Carcass characteristics were collected after a 48-h chill. Dry
      matter intake (linear, P = 0.004) and ADG (quadratic, P = 0.05) increased with
      increasing concentrations of glycerin in the diet during the first 14 d of the
      feeding period. Similarly, G:F tended to increase quadratically (P = 0.06) with
      increasing concentrations of crude glycerin in the diet during the first 14 d.
      However, there were no differences among treatments for final BW, days on feed,
      or cumulative DMI, cumulative ADG, and cumulative G:F (P >or= 0.11). Body wall
      thickness, dressing percent, HCW, LM area, flank streaking, leg score,
      conformation score, quality grade, yield grade, and percent boneless, closely
      trimmed retail cuts did not differ (P >or= 0.21). Adding up to 15% crude glycerin
      to finishing wether diets improved feedlot performance, particularly during the
      first 14 d, without any concomitant effect on carcass characteristics.

PMID- 20154166
TI  - Community and occupational health concerns in pork production: a review.
AB  - Public concerns relative to adverse consequences of large-scale livestock
      production have been increasingly voiced since the late 1960s. Numerous regional,
      national, and international conferences have been held on the subject since 1994.
      This paper provides a review of the literature on the community and occupational
      health concerns of large-scale livestock production with a focus on pork
      production. The industry has recognized the concerns of the public, and the
      national and state pork producer groups are including these issues as an
      important component of their research and policy priorities. One reason large
      scale livestock production has raised concern is that a significant component of
      the industry has separated from traditional family farming and has developed like
      other industries in management, structure, and concentration. The magnitude of
      the problem cited by environmental groups has often been criticized by the pork
      production industry for lack of science-based evidence to document environmental
      concerns. In addition to general environmental concerns, occupational health of
      workers has become more relevant because many operations now are employing more
      than 10 employees, which brings many operations in the United States under the
      scrutiny of the US Occupational Safety and Health Administration. In this paper,
      the scientific literature is reviewed relative to the science basis of
      occupational and environmental impacts on community and worker health. Further,
      recommendations are made to help promote sustainability of the livestock industry
      within the context of maintaining good stewardship of our environmental and human
      capital.

PMID- 20154167
TI  - The effect of dentition on feeding development in piglets and on their growth and
      behavior after weaning.
AB  - The objectives of this study were to determine the effects of dentition on feed
      oriented behavior and feed consumption before weaning at 28 d, and whether
      premolar eruption or occlusion at the time of weaning influenced postweaning
      growth or behavior. Over 3 trials, 24 litters of Yorkshire piglets (n = 233) were
      provided with creep feed marked with 1% chromic oxide on d 5. Dental exams were
      performed on d 2, 6, 9, 13, 16, 20, 23, and 27. Fecal samples were visually
      assessed for feed consumption (via fecal color) on the same day as dental exams,
      beginning on d 6. The duration of time spent at, and frequency of visits to, the
      creep feeder were determined from continuous video recordings on d 7, 10, 14, 17,
      21, and 24 for 6 h/d (0700 to 1000 h, 1300 to 1600 h). After weaning, behavior
      was recorded every 5 min for three 2-h time periods (0600 to 0800 h, 1100 to 1300
      h, and 1600 to 1800 h) on d 2, 4, 6, 8, 10, and 12. Piglets younger than 17 d
      with their premolars erupted and occluded spent less time at the creep feeder and
      visited it less often than piglets without their premolars erupted and occluded
      [duration: p(3) (premolar position 3 on maxilla), d 7 (P = 0.005); p(4) (premolar
      position 4 on mandible), d 7 (P < 0.0001), d 10 (P = 0.003); p(4 )(premolar
      position 4 on maxilla), d 17 (P = 0.012); occlusion, d 7 (P < 0.0001), d 10 (P =
      0.0004); visits: p(3), d 7 (P < 0.0001); p(4), d 7 (P < 0.0001), d 10 (P =
      0.001); p(3 )(premolar position 3 on mandible), d 14 (P = 0.037); p(4), d 17 (P =
      0.024); occlusion, d 7 (P < 0.0001), d 10 (P = 0.003)]. By d 21 of age, this
      trend reversed such that piglets with premolars erupted and occluded spent more
      time at the feeder and visited it more frequently [duration: p(3), d 24 (P =
      0.025); p(4), d 24 (P = 0.0005); occlusion, d 21 (P = 0.001), d 24 (P = 0.0001);
      visits: p(3), d 21 (P = 0.0002), d 24 (P < 0.0001); p(4), d 24 (P = 0.0002);
      occlusion, d 21 (P < 0.0001), d 24 (P < 0.0001)]. The percentages of piglets with
      positive fecal scores were 0, 1.4, 4.6, 8.0, 29.0, 44.9, and 60.6% on d 7, 10,
      14, 17, 21, 24, and 27, respectively (P < 0.0001 between each day). No
      associations were found between the eruption or occlusion of premolars and feed
      consumption before weaning (P > 0.05), and no dental measures influenced growth
      rates (P > 0.10) or behavior (P > 0.10) after weaning. A more precise method may
      be necessary for detecting associations between dental eruption and feed
      consumption. However, the behavioral results indicate that, before weaning at 28
      d, younger piglets are inhibited from feeding when their premolars first erupt,
      whereas older piglets with a more advanced dentition are more attracted to feed.

PMID- 20154168
TI  - Estimated gene frequencies of GeneSTAR markers and their size of effects on meat
      tenderness, marbling, and feed efficiency in temperate and tropical beef cattle
      breeds across a range of production systems.
AB  - The objectives of this study were to use genotypes for 12 commercially available
      GeneSTAR gene markers on 12,330 animals to estimate gene frequencies of the
      markers across a range of beef cattle breeds and to determine the effects of
      these markers on target traits using a subset of animals with both genotypic and
      phenotypic data (n = 9,414) for at least one trait. Tenderness markers (T1, T2,
      T3, T4) were assessed against shear force of 2 muscles, marbling markers (M1, M2,
      M3, M4) were assessed against intramuscular fat percent and marbling score, and
      the feed-efficiency markers (N1, N2, N3, N4) were assessed on daily feed intake
      and residual feed intake. Animals used were from 5 beef cattle research
      populations: Beef Cooperative Research Centre 1 (CRC1) temperate breeds (Angus,
      Hereford, Murray Grey, Shorthorn; n = 3,721), Beef CRC1 tropical breeds (Brahman,
      Santa Gertrudis, Belmont Red; n = 3,899), Beef CRC2 tropically adapted genotypes
      (Brahman and Tropical Composite; n = 4,446), and progeny test programs in Angus
      (n = 742) and Shorthorn (n = 347). Gene frequencies varied significantly across
      breeds and markers, with 86% of the markers estimated to be in Hardy-Weinberg
      equilibrium. Tenderness markers T1 and T2 had significant effects (P < 0.0001) on
      shear force, with the size and direction of effects consistent across the range
      of breeds for the 3 populations with phenotypes. However, sizes of marker effects
      differed across muscles and reduced upon tenderstretch hanging. Marker T3 was not
      significant (P > 0.05) in CRC1 temperate breeds but was significant (P < 0.0001)
      in tropically adapted breeds, with a large effect in Brahman. Marker T4 was
      significant for shear force in 2 CRC1 tropical breeds but with a different
      favorable allele. The 4 marbling markers were generally not significantly
      associated with intramuscular fat percent or marbling score across the 5
      populations studied. Feed-efficiency markers N3 and N4 were significantly
      associated with residual feed intake and daily feed intake in the CRC1 temperate
      data set, in which a subset of the CRC1 data was used in their discovery, but
      were not significant in the other 4 populations. Markers N1 and N2 were generally
      not significant, but when they were significant, their direction of effects
      differed. The 12 GeneSTAR markers were studied in populations consisting of
      different breeds and genetic variability and showed gene frequencies and
      estimated effects that varied greatly across traits, suggesting large differences
      between the markers for their utility as selection tools in these populations.

PMID- 20154169
TI  - The effects of 12, 30, or 48 hours of road transport on the physiological and
      behavioral responses of sheep.
AB  - To identify long-distance transport durations compatible with acceptable animal
      welfare, the aim of this study was to determine the responses of healthy sheep to
      road transport under good conditions for 12, 30, or 48 h. Merino ewes (n = 120;
      46.9 +/- 0.39 kg) were allocated to road transport treatments of 12, 30, or 48 h,
      with 2 replicates per treatment. Blood and urine samples and BW were taken
      pretransport and at 0, 24, 48, and 72 h posttransport. Lying time was measured
      using data loggers. Increasing transport durations resulted in reduced (P <
      0.001) BW and increased (P < 0.05) hemoconcentration, but these effects did not
      exceed clinically normal ranges for any transport duration, and sheep generally
      recovered to pretransport values within 72 h posttransport. Sheep transported for
      30 and 48 h had less BW on arrival than sheep transported for 12 h (P < 0.001).
      There were no differences (P > 0.05) between the 12- and 30-h treatments in sheep
      BW at 24, 48, or 72 h after arrival. Sheep transported for 30 and 48 h had
      greater total plasma protein concentrations on arrival than sheep transported for
      12 h (P < 0.001). Although the white cell count and neutrophil:lymphocyte ratio
      increased with transport, there were no consistent effects of transport duration.
      There were also no effects (P = 0.10) of transport duration on plasma cortisol
      concentrations. There were no treatment differences (P > 0.05) in lying times
      during the first 18 h after arrival. Sheep transported for 30 or 48 h lay down
      less (P < 0.05) than sheep transported for 12 h between 18 and 24 h after
      arrival, but there were no other differences over 72 h. These findings indicate
      that healthy adult sheep, transported under good conditions, can tolerate
      transport durations of up to 48 h without undue compromise to their welfare.

PMID- 20154170
TI  - Temperament traits of beef calves measured under field conditions and their
      relationships to performance.
AB  - A total of 3,050 German Angus (Aberdeen Angus x German dual-purpose breeds),
      Charolais, Hereford, Limousin, and German Simmental calves were used to examine
      temperament traits of beef cattle using 2 different test procedures. The chute
      test and the flight-speed test have been validated in terms of routine on-farm
      applicability. Behavior tests were performed in 2006 and 2007 on 24 commercial
      beef cattle farms located in the northern and eastern part of Germany. A single,
      trained observer assigned subjective scores to characterize the behavior of each
      animal during restraint in the head gate (calm, restless shifting, squirming,
      vigorous movement, violent struggling) and when leaving the chute (walk, trot,
      run, jumping out of the chute). Breed was a significant source of variation in
      chute scores and flight-speed scores (P < 0.001). Charolais and Limousin cattle
      had the greatest scores in both traits, whereas Herefords had the least (P <
      0.001) chute scores. German Angus and Hereford calves had the least (P < 0.001)
      flight-speeds, indicating that these breeds have a more favorable temperament.
      Temperament scores differed significantly between male and female calves (P <
      0.01), with females scoring better for both traits. Average daily BW gains of the
      calves were significantly influenced by effects of breed (P < 0.001) and sex (P <
      0.001) of the calves. Heritabilities were estimated for chute- and flight-speed
      scores of beef cattle. They were least for chute score and flight-speed score of
      Limousin cattle with values of 0.11. In contrast, greatest heritabilities were
      0.33 for chute score and 0.36 for flight-speed score of Hereford cattle. Genetic
      correlations were estimated among both temperament traits, with values between
      0.57 and 0.98. Chute scores and visual flight-speed scores were negatively
      correlated with daily BW gain of the calves in most breeds. The results presented
      in this paper indicate that on-farm evaluation of beef cattle temperament is
      possible, either using the chute test or the flight-speed test. Genetic selection
      seems to be promising to improve temperament traits of beef cattle without
      decreasing production traits like ADG of the calves.

PMID- 20154171
TI  - Calving day and age at first calving in Angus heifers.
AB  - Because of difficulties in data collection and analysis, in most breeds there
      have been limited ways to evaluate fertility in females on a between-herd basis.
      The objective of this study was to determine the heritabilities (direct and
      maternal) for CD (calving day) and AFC (age at first calving) in American Angus
      heifers and to evaluate the potential for using these traits in genetic
      improvement of female fertility. Records (n = 2,082) from 2 herds were used.
      Calving day was defined as the calving date of a heifer minus the first calving
      date in her contemporary group. To avoid bias, noncalving heifers were assigned a
      penalty record CD of 30, 60, and 90 d after the last CD in that contemporary
      group. These assigned CD were also used to give open heifers a predicted AFC.
      Data were analyzed by MTDFREML using a general linear animal model. Fixed effects
      included herd-year, service sire of the heifer, and age of dam, and a covariate
      of age of the heifer at the start of the breeding season (for CD only). A model
      including a maternal effect was also analyzed. Heritabilities for CD using a
      direct model were 0.07 +/- 0.04, 0.10 +/- 0.05, and 0.11 +/- 0.05, for each
      penalty adjustment, respectively. Average, minimum, and maximum estimated
      breeding values (in days) for sires of heifers for the 3 adjustments were -0.7, 
      10.6, and 9.8; -1.1, -17.2, and 16.5; and -1.6, -22.6, and 19.5. The estimates of
      heritability for AFC using a direct model did not differ for the different
      adjustments for penalty records and were 0.28 +/- 0.06. Average, minimum, and
      maximum estimated breeding values (in days) for sires of heifers for the 3
      adjustments were -0.6, -46.6, and 45.9; -1.2, -50.1, and 51.6; and -1.7, -52.9,
      and 56.7. In a direct-maternal model, direct heritabilities for CD decreased
      slightly, and for AFC increased to 0.66 +/- 0.14. The maternal heritabilities and
      direct-maternal genetic correlations were 0.08 +/- 0.05 and -0.18 +/- 0.58 for
      CD, and 0.32 +/- 0.08 and -0.85 +/- 0.06 for AFC. Although AFC had a greater
      heritability and a wider range of breeding values than CD, the negative direct
      maternal genetic correlation indicated that selecting on AFC may favor heifers
      that are themselves born later in the season. Therefore, CD may be more useful
      than AFC in selecting for female fertility in beef cattle.

PMID- 20154172
TI  - Response to selection for bacterial cold water disease resistance in rainbow
      trout.
AB  - A family-based selection program was initiated at the National Center for Cool
      and Cold Water Aquaculture in 2005 to improve resistance to bacterial cold water
      disease (BCWD) in rainbow trout. The objective of this study was to estimate
      response to 2 generations of selection. A total of 14,841 juvenile fish (BW = 3.1
      g; SD = 1.1 g) from 230 full-sib families and 3 randomly mated control lines were
      challenged intraperitoneally with Flavobacterium psychrophilum, the bacterium
      that causes BCWD, and mortalities were observed for 21 d. Selection was applied
      to family EBV derived from a proportional-hazards frailty (animal) model while
      constraining rate of inbreeding to <or=1% per generation. After adjusting for
      nongenetic effects, survival rate of select-line families increased by 24.6 +/-
      6.8 and 44.7 +/- 6.7 (cumulative) percentage points after 1 and 2 generations of
      selection, respectively (P < 0.01). Genetic trend, estimated from a linear animal
      model that fit genetic group effects, was 19.0 +/- 4.1 percentage points per
      generation and approached significance (P = 0.07). Heritability estimates from
      the proportional-hazards frailty model and linear animal model were similar (0.22
      and 0.23, respectively), and family EBV from both models were highly correlated (
      0.92). Accuracy of selection, estimated as the correlation between mid-parent EBV
      and progeny survival rate, was 0.20 (P < 0.01) for the proportional-hazards
      frailty model and 0.18 (P = 0.01) for the linear animal model. Accuracy estimates
      were not different (P = 0.81) between the models. This study demonstrates that
      selective breeding can be effective for improving resistance to experimental BCWD
      challenge in rainbow trout.

PMID- 20154173
TI  - Welfare applications of genetically engineered animals for use in agriculture.
AB  - The application of genetic engineering to food animals is often viewed as a means
      to further increase animal productivity without regard for the welfare of the
      resulting animals. We offer the perspective that, on the contrary, genetic
      engineering can, and is, being used to improve animal welfare in modern
      production systems. Several examples are cited from the current work in the field
      of animal genetic engineering that should be included in the debate over whether
      genetically engineered animals should be used in production agriculture. The
      current debate has slowed the advancement of this technology, which could play a
      key role in improving animal welfare and sustainability, without considering the
      potential benefits.

PMID- 20154174
TI  - Selection to reduce residual feed intake in pigs produces a correlated response
      in juvenile insulin-like growth factor-I concentration.
AB  - Data from a selection experiment for residual feed intake (RFI) were used to
      estimate genetic correlations between measures of efficiency and performance
      traits with juvenile IGF-I, and to demonstrate direct and correlated responses to
      selection. The heritability of IGF-I was 0.28 +/- 0.06 and genetic correlations
      of IGF-I with feed intake (0.26 +/- 0.17), backfat (0.52 +/- 0.11), and feed
      conversion ratio (0.78 +/- 0.14) were moderate to large. The estimated and
      realized genetic correlations between RFI and IGF-I were 0.63 +/- 0.15 and 0.84.
      In contrast, genetic correlations between IGF-I and lifetime or test period
      growth did not differ (P > 0.05) significantly from zero (0.06 +/- 0.14 and -0.19
      +/- 0.14). Selection for decreased RFI produced a direct response in RFI, as
      expected, and was accompanied by downward correlated responses in ADFI, juvenile
      IGF-I, backfat, and growth traits, listed in order of decreasing relative
      magnitude, and an increased loin muscle area. The correlated response in IGF-I to
      selection on RFI demonstrates that this physiological measure is genetically
      associated with efficiency, and is thus useful as an early information source to
      estimate genetic merit for efficiency before performance testing. Decreased
      juvenile IGF-I is associated with leaner, more efficient animals.

PMID- 20154175
TI  - Production of fertile zebrafish (Danio rerio) possessing germ cells (gametes)
      originated from primordial germ cells recovered from vitrified embryos.
AB  - This study aimed to produce fertile zebrafish (Danio rerio) possessing germ cells
      (gametes) that originated from cryopreserved primordial germ cells (PGCs). First,
      to improve the vitrification procedure of PGCs in segmentation stage embryos,
      dechorionated yolk-intact and yolk-removed embryos, the PGCs of which were
      labeled with green fluorescent protein, were cooled rapidly after serial
      exposures to equilibration solution (ES) and vitrification solution (VS), which
      contained ethylene glycol, DMSO, and sucrose. Yolk removal well prevented ice
      formation in the embryos during cooling and improved the viability of
      cryopreserved PGCs. The maximum recovery rate of live PGCs in the yolk-removed
      embryos vitrified after optimum exposure to ES and VS was estimated to be about
      90%, and about 50% of the live PGCs showed pseudopodial movement. Next, to
      elucidate the ability of cryopreserved PGCs to differentiate into functional
      gametes, PGCs recovered from the yolk-removed embryos (striped-type) that were
      vitrified under the optimum exposure to ES and VS were transplanted individually
      into 218 sterilized recipient blastulae (golden-type). Two days after the
      transplantation, 7.5% (14/187) of morphologically normal embryos had PGC(s) in
      the genital ridges. Six (5 males and 1 female) of the 14 recipient embryos
      developed into mature fish and generated progeny with characteristics inherited
      from PGC donors. In conclusion, we demonstrated the successful cryopreservation
      of PGCs by vitrification of yolk-removed embryos and the production of fertile
      zebrafish possessing germ cells that originated from the PGCs in vitrified
      embryos.

PMID- 20154176
TI  - THY1 is a conserved marker of undifferentiated spermatogonia in the pre-pubertal
      bull testis.
AB  - The undifferentiated spermatogonial population consists of stem and progenitor
      germ cells which function to provide the foundation for spermatogenesis. The stem
      cell component, termed spermatogonial stem cells (SSCs), is capable of self
      renewal and differentiation. These unique attributes have made them a target for
      novel technologies to enhance reproductive function in males. With bulls, culture
      and transplantation of SSCs have the potential to enhance efficiency of cattle
      production and provide a novel avenue to generate transgenic animals. Isolation
      of SSCs is an essential component for the development of these techniques. In
      rodents and non-human primates, undifferentiated spermatogonia and SSCs express
      the surface marker THY1. The hypothesis tested in this study was that THY1 is a
      conserved marker of the undifferentiated spermatogonial population in bulls. Flow
      cytometric analyses showed that the THY1+ cell fraction comprises a rare sub
      population in testes of pre-pubertal bulls. Immunocytochemical analyses of the
      isolated THY1+ fraction for expression of VASA showed that this cell population
      is comprised mostly of germ cells. Additionally, expression of the
      undifferentiated spermatogonial specific transcription factor promyelocytic
      leukemia zinc finger (PLZF, ZBTB16) protein was found to be enriched in the
      isolated THY1+ testis cell fraction. Lastly, xenogeneic transplantation of bull
      testis cells into seminiferous tubules of immunodeficient mice resulted in
      greater than sixfold more colonies from isolated THY1+ cells compared to the
      unselected total testis cell population indicating SSC enrichment. Collectively,
      these results demonstrate that THY1 is a marker of undifferentiated spermatogonia
      in testes of pre-pubertal bulls, and isolation of THY1+ cells results in their
      enrichment from the total testis cell population.

PMID- 20154177
TI  - The role of RXFP2 in mediating androgen-induced inguinoscrotal testis descent in
      LH receptor knockout mice.
AB  - LH receptor knockout (LhrKO) male mice exhibit a bilateral cryptorchidism
      resulting from a developmental defect in the gubernaculum during the
      inguinoscrotal phase of testis descent, which is corrected by testosterone
      replacement therapy (TRT). In vivo and in vitro experiments were conducted to
      investigate the roles of the androgen receptor (AR) and RXFP2 signals in
      regulation of gubernacular development in LhrKO animals. This study demonstrated
      that AR and RXFP2 proteins were expressed in the gubernaculum during the entire
      postnatal period. TRT normalized gubernacular RXFP2 protein levels inLhrKO mice.
      Organ and primary cell cultures of gubernacula showed that 5alpha
      dihydrotestosterone (DHT) upregulated the expression of Rxfp2 which was abolished
      by the addition of an AR antagonist, flutamide. A single s.c. testosterone
      injection also led to a significant increase in Rxfp2 mRNA levels in a time
      dependent fashion in LhrKO animals. DHT, natural and synthetic insulin-like
      peptide 3 (INSL3), or relaxin alone did not affect proliferation of gubernacular
      mesenchymal cells, while co-treatments of DHT with either INSL3 or relaxin
      resulted in an increase in cell proliferation, and they also enhanced the
      mesenchymal cell differentiation toward the myogenic pathway, which included a
      decrease in a mesenchymal cell marker, CD44 and the expression of troponin. These
      effects were attenuated by the addition of flutamide, siRNA-mediated Rxfp2
      knockdown, or by an INSL3 antagonist. Co-administration of an INSL3 antagonist
      curtailed TRT-induced inguinoscrotal testis descent in LhrKO mice. Our findings
      indicate that the RXFP2 signaling pathway plays an important role in mediating
      androgen action to stimulate gubernaculum development during inguinoscrotal
      testis descent.

PMID- 20154178
TI  - Dynamics of traditional metabolic risk factors associate with specific causes of
      death in old age.
AB  - BACKGROUND: In contrast to middle age, higher body mass index (BMI), cholesterol
      levels, and blood pressures associate no longer with increased mortality in old
      age. With increasing age, these risk factors are prone to change over time. It is
      unclear whether dynamics of these traditional metabolic risk factors in late life
      associate with mortality and whether they occur in concert with each other.
      METHODS: Within the Leiden 85-plus Study, a prospective population-based study of
      599 participants aged 85 years, participants were annually assessed during a 5
      year follow-up period and observed for mortality for 10 years. RESULTS: BMI,
      total cholesterol levels, glucose levels, and blood pressures declined and HDL
      cholesterol levels increased between ages 85 and 90 years (all p < .005).
      Participants who died at age 90 years had stronger annual declines in BMI, total
      cholesterol levels, and diastolic blood pressure and weaker increases in HDL
      cholesterol levels than participants who survived until the end of follow-up (all
      p < or = .001). In a principal component analysis, annual changes in total, LDL,
      and HDL cholesterol levels; blood pressures; and glucose, albumin, hemoglobin,
      leukocyte, and C-reactive protein levels grouped together in one component (all
      correlation r with component >.40), which associated with all-cause and cancer
      mortality. CONCLUSIONS: In old age, larger declines in BMI, total cholesterol
      levels, and blood pressures and weaker increases in HDL cholesterol levels
      associate with mortality. We identified distinct clustering in the dynamics of
      these traditional metabolic risk factors and indicators of health and disease in
      a profile that is suggestive of underlying wasting disease.

PMID- 20154179
TI  - Impaired depth perception and restricted pitch head movement increase obstacle
      contacts when dual-tasking in older people.
AB  - BACKGROUND: Trips are the largest contributor to falls in older people, yet
      little is known about the underlying physiological mechanisms for safe obstacle
      negotiation. The aims of the study were to determine (i) the effect of a
      secondary visual task on obstacle contacts when older people negotiated an
      obstacle course and (ii) physiological factors associated with obstacle contacts.
      METHODS: Thirty community-living adults aged 65 years and older walked along a
      14.5-m walkway containing 21 obstacles with and without a secondary task. The
      secondary task required participants to call out a series of letters presented in
      front of them at head height and the suit of a playing card framed on the
      sidewall. Obstacle contacts, secondary task errors, eye peak-to-peak pitch
      amplitude and head peak-to-peak pitch amplitude (PA-H), and head angle in pitch
      were measured. Participants also completed assessments of sensorimotor function
      and balance. RESULTS: Compared with the obstacle-only trials, participants
      performed the dual-task trials more slowly (p < .001), contacted more obstacles
      (p = .032), showed greater PA-H (p < .001), and an extended head position (p <
      .001). Most participants also made secondary task errors. Regression analysis
      revealed that depth perception was the only significant determinant of obstacle
      contacts (explaining 20.6% of the variance) in the obstacle-only task and that
      depth perception and PA-H were independent and significant determinants of
      obstacle contacts (explaining 42.3% of the variance) in the dual task.
      CONCLUSION: The findings demonstrate the importance of depth perception and head
      movement for safe negotiation of obstacles in older people and suggest that depth
      perception in particular should form part of fall risk assessments.

PMID- 20154180
TI  - First-order correct bootstrap support adjustments for splits that allow
      hypothesis testing when using maximum likelihood estimation.
AB  - The most frequent measure of phylogenetic uncertainty for splits is bootstrap
      support. Although large bootstrap support intuitively suggests that a split in a
      tree is well supported, it has not been clear how large bootstrap support needs
      to be to conclude that there is significant evidence that a hypothesized split is
      present. Indeed, recent work has shown that bootstrap support is not first-order
      correct and thus cannot be directly used for hypothesis testing. We present
      methods that adjust bootstrap support values in a maximum likelihood (ML) setting
      so that they have an interpretation corresponding to P values in conventional
      hypothesis testing; for instance, adjusted bootstrap support larger than 95%
      occurs only 5% of the time if the split is not present. Through examples and
      simulation settings, it is found that adjustments always increase the level of
      support. We also find that the nature of the adjustment is fairly constant across
      parameter settings. Finally, we consider adjustments that take into account the
      data-dependent nature of many hypotheses about splits: the hypothesis that they
      are present is being tested because they are in the tree estimated through ML.
      Here, in contrast, we find that bootstrap probability often needs to be adjusted
      downwards.

PMID- 20154181
TI  - Understanding the vertebrate immune system: insights from the reptilian
      perspective.
AB  - Reptiles are ectothermic amniotes, providing the key link between ectothermic
      anamniotic fishes and amphibians, and endothermic amniotic birds and mammals. A
      greater understanding of reptilian immunity will provide important insights into
      the evolutionary history of vertebrate immunity as well as the growing field of
      eco-immunology. Like mammals, reptile immunity is complex and involves innate,
      cell-mediated and humoral compartments but, overall, there is considerably less
      known about immune function in reptiles. We review the current literature on each
      branch of the reptilian immune system, placing this information in context to
      other vertebrates. Further, we identify key areas that are prime for research as
      well as areas that are lagging because of lack of reagents in non-model systems.

PMID- 20154182
TI  - Venom kinematics during prey capture in Conus: the biomechanics of a rapid
      injection system.
AB  - Cone snails use an extensile, tubular proboscis as a conduit to deliver a potent
      cocktail of bioactive venom peptides into their prey. Previous studies have
      focused mainly on understanding the venom's role in prey capture but successful
      prey capture requires both rapid physiological and biomechanical mechanisms.
      Conus catus, a fish-hunting species, uses a high-speed hydraulic mechanism to
      inject its hollow, spear-like radular tooth into prey. We take an integrated
      approach to investigating the biomechanics of this process by coupling kinematic
      studies with morphological analyses. Taking advantage of the opaque venom and
      translucent proboscis of a mollusc-hunting juvenile cone snail, Conus pennaceus,
      we have determined that a high-speed prey capture mechanism is not unique to cone
      species that hunt fish prey. Two morphological structures were found to play
      crucial roles in this process. A constriction of the lumen near the tip of the
      proboscis, composed of tall epithelial cells densely packed with microfilaments,
      impedes forward movement of the radular tooth prior to its propulsion. Proximal
      to the constriction, a muscular sphincter was found to regulate venom flow and
      pressurization in the proboscis. In C. pennaceus, the rapid appearance and
      flushing of venom within the proboscis during prey capture suggests a mechanism
      involving the delivery of a discrete quantity of venom. The interplay between
      these elements provides a unique and effective biomechanical injection system for
      the fast-acting cone snail venom peptides.

PMID- 20154184
TI  - Biomechanics of locomotion in Asian elephants.
AB  - Elephants are the biggest living terrestrial animal, weighing up to five tons and
      measuring up to three metres at the withers. These exceptional dimensions provide
      certain advantages (e.g. the mass-specific energetic cost of locomotion is
      decreased) but also disadvantages (e.g. forces are proportional to body volume
      while supportive tissue strength depends on their cross-sectional area, which
      makes elephants relatively more fragile than smaller animals). In order to
      understand better how body size affects gait mechanics the movement of the centre
      of mass (COM) of 34 Asian elephants (Elephas maximus) was studied over their
      entire speed range of 0.4-5.0 m s(-1) with force platforms. The mass-specific
      mechanical work required to maintain the movements of the COM per unit distance
      is approximately 0.2 J kg(-1) m(-1) (about 1/3 of the average of other animals
      ranging in size from a 35 g kangaroo rat to a 70 kg human). At low speeds this
      work is reduced by a pendulum-like exchange between the kinetic and potential
      energies of the COM, with a maximum energy exchange of approximately 60% at 1.4 m
      s(-1). At high speeds, elephants use a bouncing mechanism with little exchange
      between kinetic and potential energies of the COM, although without an aerial
      phase. Elephants increase speed while reducing the vertical oscillation of the
      COM from about 3 cm to 1 cm.

PMID- 20154183
TI  - Chloride channel ClC-3 in gills of the euryhaline teleost, Tetraodon
      nigroviridis: expression, localization and the possible role of chloride
      absorption.
AB  - Previous studies have reported the mechanisms of ion absorption and secretion by
      diverse membrane transport proteins in gills of various teleostean species. To
      date, however, the chloride channel expressed in the basolateral membrane of
      mitochondrion-rich (MR) cells for Cl(-) uptake in freshwater (FW) fish is still
      unknown. In this study, the combination of bioinformatics tools [i.e. National
      Center for Biotechnology Information (NCBI) database, Tetraodon nigroviridis
      (spotted green pufferfish) genome database (Genoscope), BLAT and BLASTn] were
      used to identify the gene of ClC-3 (TnClC-3), a member of the CLC chloride
      channel family in the T. nigroviridis genome. RT-PCR analysis revealed that the
      gene encoding for the ClC-3 protein was widely expressed in diverse tissues (i.e.
      gill, kidney, intestine, liver and brain) of FW- and seawater (SW)-acclimated
      pufferfish. In whole-mount double immunofluorescent staining, branchial ClC-3
      like immunoreactive protein was localized to the basolateral membrane of
      Na(+)/K(+)-ATPase (NKA) immunoreactive cells in both the FW- and SW-acclimated
      pufferfish. In response to salinity, the levels of transcript of branchial TnClC
      3 were similar between FW and SW fish. Moreover, the membrane fraction of ClC-3
      like protein in gills was 2.7-fold higher in FW compared with SW pufferfish. To
      identify whether the expression of branchial ClC-3-like protein specifically
      responded to lower environmental [Cl(-)], the pufferfish were acclimated to
      artificial waters either with a normal (control) or lower Cl(-) concentration
      (low-Cl). Immunoblotting of membrane fractions of gill ClC-3-like protein showed
      the expression was about 4.3-fold higher in pufferfish acclimated to the low-Cl
      environment than in the control group. Furthermore, branchial ClC-3-like protein
      was rapidly elevated in response to acute changes of environmental salinity or
      [Cl(-)]. Taken together, pufferfish ClC-3-like protein was expressed in the
      basolateral membrane of gill MR cells, and the protein amounts were stimulated by
      hyposmotic and low-Cl environments. The enhancement of ClC-3-like protein may
      trigger the step of basolateral Cl(-) absorption of the epithelium to carry out
      iono- and osmoregulatory functions of euryhaline pufferfish gills.

PMID- 20154185
TI  - The influence of tendon compliance on muscle power output and efficiency during
      cyclic contractions.
AB  - Muscle power output and efficiency during cyclical contractions are influenced by
      the timing and duration of stimulation of the muscle and the interaction of the
      muscle with its mechanical environment. It has been suggested that tendon
      compliance may reduce the energy required for power production from the muscle by
      reducing the required shortening of the muscle fibres. Theoretically this may
      allow the muscle to maintain both high power output and efficiency during
      cyclical contraction; however, this has yet to be demonstrated experimentally. To
      investigate how tendon compliance might act to increase muscle power output
      and/or efficiency, we attached artificial tendons of varying compliance to muscle
      fibre bundles in vitro and measured power output and mechanical efficiency during
      stretch-shorten cycles (2 Hz) with a range of stretch amplitudes and stimulation
      patterns. The results showed that peak power, average power output and efficiency
      (none of which can have direct contributions from the compliant tendon) all
      increased with increasing tendon compliance, presumably due to the tendon acting
      to minimise muscle energy use by allowing the muscle fibres to shorten at optimal
      speeds. Matching highly compliant tendons with a sufficiently large amplitude
      length change and appropriate stimulation pattern significantly increased the net
      muscle efficiency compared with stiff tendons acting at the same frequency. The
      maximum efficiency for compliant tendons was also similar to the highest value
      measured under constant velocity and force conditions, which suggests that tendon
      compliance can maximise muscle efficiency in the conditions tested here. These
      results provide experimental evidence that during constrained cyclical
      contractions, muscle power and efficiency can be enhanced with compliant tendons.

PMID- 20154186
TI  - Mounting a specific immune response increases energy expenditure of the
      subterranean rodent Ctenomys talarum (tuco-tuco): implications for intraspecific
      and interspecific variation in immunological traits.
AB  - It was recently hypothesised that specific induced defences, which require
      substantial time and resources and are mostly beneficial against repeated
      infections, are more likely to be favoured in 'slow-living-pace' species.
      Therefore, understanding how different types of immune defences might vary with
      life history requires knowledge of the costs and benefits of defence components.
      Studies that have explored the energetic costs of immunity in vertebrates have
      done so with a focus primarily on birds and less so on mammals, particularly
      surface-dwelling rodents. In this study, we evaluated whether an experimental
      induction of the immune system with a non-pathogenic antigen elevates the
      energetic expenditure of a subterranean rodent: Ctenomys talarum (tuco-tucos). In
      both seasons studied, a significant increase in oxygen consumption was verified
      in immune-challenged tuco-tucos injected with sheep red blood cells (SRBC)
      compared with control animals. The increase in oxygen consumption 10 days after
      the exposure to SRBC was lower for female tuco-tucos monitored in the breeding
      season compared with females in the non-breeding season. Interestingly, antibody
      titres of female tuco-tucos did not decrease during the breeding season. Our
      results add new insight into the role of other factors such as basal metabolic
      rate or degree of parasite exposure besides 'pace of life' in modulating the
      interspecific immunological variation observed in natural populations of mammals.

PMID- 20154187
TI  - Allometry of hummingbird lifting performance.
AB  - Vertical lifting performance in 67 hummingbird species was studied across a 4000
      m elevational gradient. We used the technique of asymptotic load-lifting to
      elicit maximum sustained muscle power output during loaded hovering flight. Our
      analysis incorporated direct measurements of maximum sustained load and
      simultaneous wingbeat kinematics, together with aerodynamic estimates of mass
      specific mechanical power output, all within a robust phylogenetic framework for
      the Trochilidae. We evaluated key statistical factors relevant to estimating
      slopes for allometric relationships by performing analyses with and without
      phylogenetic information, and incorporating species-specific measurement error.
      We further examined allometric relationships at different elevations because this
      gradient represents a natural experiment for studying physical challenges to
      animal flight mechanics. Maximum lifting capacity (i.e. vertical force
      production) declined with elevation, but was either isometric or negatively
      allometric with respect to both body and muscle mass, depending on elevational
      occurrence of the corresponding taxa. Maximum relative muscle power output
      exhibited a negative allometry with respect to muscle mass, supporting
      theoretical predictions from muscle mechanics.

PMID- 20154188
TI  - Fitness costs may explain the post-colonisation erosion of phenotypic plasticity.
AB  - Many organisms can adjust their phenotypes to match local environmental
      conditions via shifts in developmental trajectories, rather than relying on
      changes in gene frequencies wrought by natural selection. Adaptive developmental
      plasticity confers obvious benefits in terms of rapid response and higher mean
      fitness, so why is it not more common? Plausibly, adaptive plasticity also
      confers a cost; reshaping the phenotype takes time and energy, so that canalised
      control of trait values enhances fitness if the optimal phenotype remains the
      same from one generation to the next. Although this idea is central to
      interpreting the fitness consequences of adaptive plasticity, empirical data on
      costs of plasticity are scarce. In Australian tiger snakes, larger relative head
      size enhances maximal ingestible prey size on islands containing large prey. The
      trait arises via adaptive plasticity in snake populations on newly colonised
      islands but becomes genetically canalised on islands where snakes have been
      present for much longer periods. We experimentally manipulated relative head size
      in captive neonatal snakes to quantify the costs of adaptive plasticity. Although
      small-headed snakes were able to increase their head sizes when offered large
      prey, the delay in doing so, and their inability to consume large prey at the
      outset, significantly reduced their growth rates relative to conspecifics with
      larger heads at the beginning of the experiment. This study describes a proximate
      cause to the post-colonisation erosion of developmental plasticity recorded in
      tiger snake populations.

PMID- 20154189
TI  - Development of aerobic and anaerobic metabolism in cardiac and skeletal muscles
      from harp and hooded seals.
AB  - In diving animals, skeletal muscle adaptations to extend underwater time despite
      selective vasoconstriction include elevated myoglobin (Mb) concentrations, high
      acid buffering ability (beta) and high aerobic and anaerobic enzyme activities.
      However, because cardiac muscle is perfused during dives, it may rely less
      heavily on Mb, beta and anaerobic pathways to support contractile activity. In
      addition, because cardiac tissue must sustain contractile activity even before
      birth, it may be more physiologically mature at birth and/or develop faster than
      skeletal muscles. To test these hypotheses, we measured Mb levels, beta and the
      activities of citrate synthase (CS), beta-hydroxyacyl-CoA dehydrogenase (HOAD)
      and lactate dehydrogenase (LDH) in cardiac and skeletal muscle samples from 72
      harp and hooded seals, ranging in age from fetuses to adults. Results indicate
      that in adults cardiac muscle had lower Mb levels (14.7%), beta (55.5%) and LDH
      activity (36.2%) but higher CS (459.6%) and HOAD (371.3%) activities (all P<0.05)
      than skeletal muscle. In addition, while the cardiac muscle of young seals had
      significantly lower [Mb] (44.7%) beta (80.7%) and LDH activity (89.5%) than
      adults (all P<0.05), it was relatively more mature at birth and weaning than
      skeletal muscle. These patterns are similar to those in terrestrial species,
      suggesting that seal hearts do not exhibit unique adaptations to the challenges
      of an aquatic existence.

PMID- 20154190
TI  - Gene expression profiling of genetically determined growth variation in bivalve
      larvae (Crassostrea gigas).
AB  - Growth rates in animals are governed by a wide range of biological factors, many
      of which remain poorly understood. To identify the genes that establish growth
      differences in bivalve larvae, we compared expression patterns in contrasting
      phenotypes (slow- and fast-growth) that were experimentally produced by genetic
      crosses of the Pacific oyster Crassostrea gigas. Based on transcriptomic
      profiling of 4.5 million cDNA sequence tags, we sequenced and annotated 181 cDNA
      clones identified by statistical analysis as candidates for differential growth.
      Significant matches were found in GenBank for 43% of clones (N=78), including 34
      known genes. These sequences included genes involved in protein metabolism,
      energy metabolism and regulation of feeding activity. Ribosomal protein genes
      were predominant, comprising half of the 34 genes identified. Expression of
      ribosomal protein genes showed non-additive inheritance - i.e. expression in fast
      growing hybrid larvae was different from average levels in inbred larvae from
      these parental families. The expression profiles of four ribosomal protein genes
      (RPL18, RPL31, RPL352 and RPS3) were validated by RNA blots using additional,
      independent crosses from the same families. Expression of RPL35 was monitored
      throughout early larval development, revealing that these expression patterns
      were established early in development (in 2-day-old larvae). Our findings (i)
      provide new insights into the mechanistic bases of growth and highlight genes not
      previously considered in growth regulation, (ii) support the general conclusion
      that genes involved in protein metabolism and feeding regulation are key
      regulators of growth, and (iii) provide a set of candidate biomarkers for
      predicting differential growth rates during animal development.

PMID- 20154191
TI  - Insect form vision as one potential shaping force of spider web decoration
      design.
AB  - Properties of prey sensory systems are important factors shaping the design of
      signals generated by organisms exploiting them. In this study we assessed how
      prey sensory preference affected the exploiter signal design by investigating the
      evolutionary relationship and relative attractiveness of linear and cruciate form
      web decorations built by Argiope spiders. Because insects have an innate
      preference for bilaterally symmetrical patterns, we hypothesized that cruciate
      form decorations were evolved from linear form due to their higher visual
      attractiveness to insects. We first reconstructed a molecular phylogeny of the
      Asian members of the genus Argiope using mitochondrial markers to infer the
      evolutionary relationship of two decoration forms. Results of ancestral character
      state reconstruction showed that the linear form was ancestral and the cruciate
      form derived. To evaluate the luring effectiveness of two decoration forms, we
      performed field experiments in which the number and orientation of decoration
      bands were manipulated. Decoration bands arranged in a cruciate form were
      significantly more attractive to insects than those arranged in a linear form, no
      matter whether they were composed of silks or dummies. Moreover, dummy decoration
      bands arranged in a cruciate form attracted significantly more insects than those
      arranged in a vertical/horizontal form. Such results suggest that pollinator
      insects' innate preference for certain bilateral or radial symmetrical patterns
      might be one of the driving forces shaping the arrangement pattern of spider web
      decorations.

PMID- 20154192
TI  - Dual control of cytosolic metals by lysosomal transporters in lobster
      hepatopancreas.
AB  - This study describes the membrane transport mechanisms used by lobster (Homarus
      americanus) hepatopancreatic epithelial lysosomes to accumulate and sequester
      heavy metals from the cytosol, and thereby aid in the regulation of these ions
      entering the animal from dietary constituents. The present investigation extends
      previous work describing lysosomal metal uptake by cation exchange with protons
      and suggests that a second, parallel, lysosomal transport process involving metal
      thiol conjugates may work in conjunction with the cation antiporter to control
      cytoplasmic metal concentrations. Transport of (65)Zn(2+) by lysosomal membrane
      vesicles (LMV) incubated in 1 mmol l(-1) glutathione (GSH) was not significantly
      different from metal transport in the absence of the tripeptide. However,
      preloading LMV with 1 mmol l(-1) alpha-ketoglutarate (AKG), and then incubating
      in a medium containing 1 mmol l(-1) GSH, more than doubled metal uptake, compared
      with vesicles equilibrated with chloride or possessing an outwardly directed
      chloride gradient. Kinetic analysis of lysosomal (65)Zn(2+) influx as a function
      of zinc concentration, in vesicles containing 1 mmol l(-1) AKG and incubated in 1
      mmol l(-1) GSH, revealed the presence of a sigmoidal, low affinity, high capacity
      carrier process transporting the metal into the organelle. These data indicated
      the possible presence of an organic anion exchanger in lobster lysosomal
      membranes. Western blot analysis of LMV with a rabbit anti-rat OAT1 antibody
      showed the presence of an orthologous OAT1-like protein (approximate molecular
      mass of 80 kDa) signal from these membranes. These results, and those published
      previously, suggest the occurrence of two metal transporters on hepatopancreatic
      membranes, a high affinity, low capacity cation antiporter and a low affinity,
      high capacity organic anion exchanger. Together these two systems have the
      potential to regulate cytoplasmic metals over a wide concentration range.

PMID- 20154193
TI  - Changes in rabbit jaw-muscle activity parameters in response to reduced
      masticatory load.
AB  - Mechanical food properties influence the neuromuscular activity of jaw-closing
      muscles during mastication. It is, however, unknown how the activity profiles of
      the jaw muscles are influenced by long-term alterations in masticatory load. In
      order to elucidate the effect of reduced masticatory load on the daily habitual
      activity profiles of three functionally different jaw muscles, the
      electromyograms of the masseter, temporalis and digastric muscles were recorded
      telemetrically in 16 male rabbits between seven and 20 weeks of age. Starting at
      eight weeks of age the experimental animals were fed significantly softer pellets
      than the control animals. Daily muscle activity was quantified by the relative
      duration of muscle use (duty time), burst number and burst length in relation to
      multiple activity levels. The daily duty time and burst number of the masseter
      muscle were significantly lower in the experimental group than in the control
      group at 5% and 10% of the maximum activity during the two weeks following the
      change in food hardness. By contrast, altered food hardness did not significantly
      influence the activity characteristics of the temporalis and digastric muscles.
      The findings suggest that a reduction in masticatory load decreases the
      neuromuscular activity of the jaw-closing muscles that are primarily responsible
      for force generation during mastication. This decrease is most pronounced in the
      weeks immediately following the change in food hardness and is limited to the
      activity levels that reflect muscle contractions during chewing. These findings
      support the conclusion that the masticatory system manifests few diet-specific
      long-term changes in the activity profiles of jaw muscles.

PMID- 20154194
TI  - Tracking the oxidative kinetics of carbohydrates, amino acids and fatty acids in
      the house sparrow using exhaled 13CO2.
AB  - Clinicians commonly measure the (13)CO(2) in exhaled breath samples following
      administration of a metabolic tracer (breath testing) to diagnose certain
      infections and metabolic disorders. We believe that breath testing can become a
      powerful tool to investigate novel questions about the influence of ecological
      and physiological factors on the oxidative fates of exogenous nutrients. Here we
      examined several predictions regarding the oxidative kinetics of specific
      carbohydrates, amino acids and fatty acids in a dietary generalist, the house
      sparrow (Passer domesticus). After administering postprandial birds with 20 mg of
      one of seven (13)C-labeled tracers, we measured rates of (13)CO(2) production
      every 15 min over 2 h. We found that sparrows oxidized exogenous amino acids far
      more rapidly than carbohydrates or fatty acids, and that different tracers
      belonging to the same class of physiological fuels had unique oxidative kinetics.
      Glycine had a mean maximum rate of oxidation (2021 nmol min(-1)) that was
      significantly higher than that of leucine (351 nmol min(-1)), supporting our
      prediction that nonessential amino acids are oxidized more rapidly than essential
      amino acids. Exogenous glucose and fructose were oxidized to a similar extent
      (5.9% of dose), but the time required to reach maximum rates of oxidation was
      longer for fructose. The maximum rates of oxidation were significantly higher
      when exogenous glucose was administered as an aqueous solution (122 nmol min(
      1)), rather than as an oil suspension (93 nmol min(-1)), supporting our
      prediction that exogenous lipids negatively influence rates of exogenous glucose
      oxidation. Dietary fatty acids had the lowest maximum rates of oxidation (2-6
      nmol min(-1)), and differed significantly in the extent to which each was
      oxidized, with 0.73%, 0.63% and 0.21% of palmitic, oleic and stearic acid tracers
      oxidized, respectively.

PMID- 20154195
TI  - The influence of foot posture on the cost of transport in humans.
AB  - Although humans appear to be specialized for endurance running, the plantigrade
      posture of our feet, in which the heel contacts the substrate at the beginning of
      a step, seems incompatible with economical running. In this study, we tested the
      hypothesis that plantigrade foot posture reduces the energetic cost of transport
      (COT) during walking in humans. When human subjects walked with their heels
      slightly elevated in a 'low-digitigrade' posture, COT increased by 53% above that
      of normal plantigrade walking. By contrast, there was no difference in COT when
      subjects ran with digitigrade versus plantigrade foot posture. Stride frequency
      increased and stride length decreased when subjects switched to digitigrade
      walking; however, this change did not influence the COT. Additionally, we found
      that possible reductions in postural stability appear not to have caused the
      elevated cost of digitigrade walking. Digitigrade walking, however, did (1)
      increase the external mechanical work performed by the limbs; (2) reduce the
      pendular exchange of kinetic and potential energy of the center of mass; (3)
      increase the average ground reaction force moment at the ankle joint; and (4)
      increase the recruitment of major extensor muscles of the ankle, knee, hip and
      back. These observations suggest that plantigrade foot posture improves the
      economy of walking. Relative to other mammals, humans are economical walkers, but
      not economical runners. Given the great distances hunter-gatherers travel, it is
      not surprising that humans retained a foot posture, inherited from our more
      arboreal great ape ancestors, that facilitates economical walking.

PMID- 20154196
TI  - Low plasticity in digestive physiology constrains feeding ecology in diet
      specialist, zebra finch (Taeniopygia guttata).
AB  - It can be hypothesized that species with a wide or variable food niche are able
      to adjust their digestive physiology to current food type. In diet specialists,
      however, the capacity for such presumably costly plasticity is not necessary and
      flexibility of digestive physiology should be lower. Recently, we found that
      ontogenetic changes in the activity of digestive enzymes in house sparrow, a
      species that gradually consumes more carbohydrates during ontogeny, are strongly
      modified by diet composition. In the present study we examined digestive
      flexibility of nestling and adult zebra finches, typical diet specialists that
      consume only seeds after hatching. Both adult and nestling zebra finches could
      not thrive on a protein-rich and carbohydrate-free diet that supported normal
      development of young house sparrows. Mass-specific activity of intestinal
      carbohydrases (maltase and sucrase) was not elevated by higher diet carbohydrate
      content in both nestling and adult birds. Mass-specific activity of maltase
      changed less during ontogenetic development in zebra finch than in house sparrow.
      We conclude that the digestive physiology of zebra finch is adapted to process
      carbohydrate-rich food after hatching and is much less flexible than in house
      sparrow. We hypothesize that this difference might reflect the lack of a diet
      switch during ontogeny or result from high specialization to a narrow diet niche.

PMID- 20154198
TI  - In situ cardiac function in Atlantic cod (Gadus morhua): effects of acute and
      chronic hypoxia.
AB  - Recent in vivo experiments on Atlantic cod (Gadus morhua) acclimated to chronic
      hypoxia (6-12 weeks at 10 degrees C; Pw(O(2)) approximately 8-9 kPa) revealed a
      considerable decrease in the pumping capacity of the heart. To examine whether
      this diminished cardiac performance was due to the direct effects of chronic
      moderate hypoxia on the myocardium (as opposed to alterations in neural and/or
      hormonal control), we measured the resting and maximum in situ function of hearts
      from normoxia- and hypoxia-acclimated cod: (1) when initially perfused with
      oxygenated saline; (2) at the end of a 15 min exposure to severe hypoxia (P(O(2))
      approximately 0.6 kPa); and (3) 30 min after the hearts had been reperfused with
      oxygenated saline. Acclimation to hypoxia did not influence resting (basal) in
      situ cardiac performance during oxygenated or hypoxic conditions. However, it
      caused a decrease in maximum cardiac output (Q(max)) under oxygenated conditions
      (from 49.5 to 40.3 ml min(-1) kg(-1); by 19%), that was due to diminished values
      for maximum stroke volume (V(S)) and scope for V(S). Severe hypoxia reduced in
      both groups to approximately 20 ml min(-1) kg(-1), yet, the hearts of hypoxia
      acclimated fish were better able to sustain this level of Q under hypoxia, and
      the recovery of Q(max) (as compared with initial values under oxygenated
      conditions) was significantly improved (94% vs 83%). These data show that
      acclimation to hypoxia has a direct effect on cod myocardial function and/or
      physiology, and suggest that the cod heart shows some adaptations to prolonged
      hypoxia.

PMID- 20154197
TI  - Effect of acute and chronic hypoxia on the swimming performance, metabolic
      capacity and cardiac function of Atlantic cod (Gadus morhua).
AB  - Low water oxygen content (hypoxia) is a common feature of many freshwater and
      marine environments. However, we have a poor understanding of the degree to which
      diminished cardiac function contributes to the reduction in fish swimming
      performance concomitant with acute exposure to hypoxia, or how fish
      cardiorespiratory physiology is altered by, or adapts to, chronic hypoxia. Thus,
      we acclimated adult Atlantic cod (Gadus morhua) to either approximately 8-9 kPa
      O(2) (40-45% air saturation) or approximately 21 kPa O(2) (100% air saturation;
      normoxia) for 6-12 weeks at 10 degrees C, and subsequently measured metabolic
      variables [routine oxygen consumption (M(O(2)), maximum (M(O(2)), metabolic
      scope] and cardiac function (cardiac output, Q; heart rate, f(H); and stroke
      volume, V(S)) in these fish during critical swimming speed (U(crit)) tests
      performed at both levels of water oxygenation. Although surgery (flow probe
      implantation) reduced the U(crit) of normoxia-acclimated cod by 14% (from 1.74 to
      1.50 BL s(-1)) under normoxic conditions, exposure to acute hypoxia lowered the
      U(crit) of both groups (surgery and non-surgery) by approximately 30% (to 1.23
      and 1.02 BL s(-1), respectively). This reduction in swimming performance was
      associated with large decreases in maximum M(O(2)) and metabolic scope (> or =
      50%), and maximum f(H) and Q (by 16 and 22%), but not V(S). Long-term acclimation
      to hypoxia resulted in a significant elevation in normoxic metabolic rate as
      compared with normoxia-acclimated fish (by 27%), but did not influence normoxic
      or hypoxic values for U(crit), maximum M(O(2)) or metabolic scope. This was
      surprising given that resting and maximum values for Q were significantly lower
      in hypoxia-acclimated cod at both levels of oxygenation, because of lower values
      for V(S). However, hypoxia-acclimated cod were able to consume more oxygen for a
      given cardiac output. These results provide important insights into how fish
      cardiorespiratory physiology is impacted by short-term and prolonged exposure to
      hypoxia, and further highlight the tremendous capacity of the fish
      cardiorespiratory system to deal with environmental challenges.

PMID- 20154199
TI  - Muscle activity and hydrodynamic function of pelvic fins in trout (Oncorhynchus
      mykiss).
AB  - Contrary to the previous premise that pelvic fins lacked obvious function, recent
      work on three-dimensional fin motions suggests that pelvic fins actively control
      stability and speed in slowly swimming trout. This study used electromyography to
      measure pelvic fin muscle activity and particle imaging velocimetry to quantify
      flow along the ventral body region to test this hypothesis. Fish swam at slow
      speeds (0.13-1.36 BL s(-1)) while being filmed with three high speed cameras.
      Three-dimensional kinematics were captured for all trials. During EMG trials
      pelvic fin muscle activity was synchronized to kinematic motion, during particle
      imaging velocimetry trials, a laser light-sheet was used to visualize the flow
      surrounding the ventral aspect of the fish. Four main conclusions are reached:
      first, pelvic fins are actively oscillated during slow-speed swimming;
      antagonistic abductor and adductor muscles contracted simultaneously, their
      collective action producing a unique contralateral oscillating behaviour in the
      fins. Second, pelvic fins slow the flow along the ventral side affecting pitch
      and yaw instabilities; flow upstream of the pelvic fins is slowed by 0.02 m s(-1)
      and flow downstream of the pelvic fins is slowed by 0.034 m s(-1) compared with
      free stream flow. Third, pelvic fin wake influences anal fin angle of attack;
      flow angle in the wake of the pelvic fin was 33.84+/-2.4 deg. (max) and -11.83+/
      11.2 deg. (min) compared with the free stream flow angle of 1.27+/-0.1 deg.
      Fourth, pelvic fins appear to actively damp body oscillation during slow-speed
      swimming, providing drag to help control speed and stabilize the body position
      during slow-speed swimming.

PMID- 20154200
TI  - Perfusion with cAMP analogue affects pheromone-sensitive trichoid sensilla of the
      hawkmoth Manduca sexta in a time-dependent manner.
AB  - Octopamine causes time-dependent disadaptation of pheromone-sensitive olfactory
      receptor neurons (ORNs) of Manduca sexta. Because the majority of insect
      octopamine receptors are positively coupled to adenylyl cyclases we examined
      whether cyclic adenosine monophosphate (cAMP) mimics octopamine-dependent
      modulation of pheromone transduction in a time-dependent manner. Long-term tip
      recordings of single trichoid sensilla of Manduca sexta were performed during
      three zeitgeber times (ZTs, ZT 0=lights on), while stimulating the sensilla with
      two doses of the main pheromone component bombykal in a non-adapting protocol.
      The membrane-permeable cAMP analogue 8bcAMP increased the normalized sensillar
      potential amplitude in a time- and bombykal dose-dependent way. At the higher
      bombykal dose only, the applied 8bcAMP antagonized an endogenous decrease in the
      mean sensillar potential amplitude at ZT 1-4 and ZT 8-11 when ORNs were adapted
      but not at ZT 22-1, when ORNs were sensitized. In contrast to octopamine, 8bcAMP
      did not consistently affect the initial pheromone-dependent action potential
      frequency, the phasic/tonic response pattern, or the time-dependent shift to
      lower mean action potential frequencies at ZT 8-11. Furthermore, 8bcAMP increased
      the spontaneous action potential frequency time dependently, but differently from
      octopamine. In conclusion, our results show that cAMP only partly mimics the
      octopamine-dependent disadaptation of olfactory receptor neurons during
      photophase, apparently due to another missing octopamine-dependent synergistic
      factor such as defined intracellular calcium levels.

PMID- 20154202
TI  - Mutant mouse models: phenotypic relationships to domains of psychopathology and
      pathobiology in schizophrenia.
AB  - The present series of review articles seeks to elaborate how current findings in
      mutant mice may inform on the relationship between candidate genes and individual
      psychopathological and pathobiological aspects of schizophrenia. Each of the
      authors focuses on an overlapping selection of both well-characterized and
      emergent candidate genes, as identified through association and linkage studies
      and/or via their involvement in putative pathophysiological mechanisms,
      particularly those relating to dopaminergic and glutamatergic processes.

PMID- 20154201
TI  - The neural underpinnings of associative learning in health and psychosis: how can
      performance be preserved when brain responses are abnormal?
AB  - Associative learning experiments in schizophrenia and other psychoses reveal
      subtle abnormalities in patients' brain responses. These are sometimes
      accompanied by intact task performance. An important question arises: How can
      learning occur if the brain system is not functioning normally? Here, we examine
      a series of possible explanations for this apparent discrepancy: (1) standard
      brain activation patterns may be present in psychosis but partially obscured by
      greater noise, (2) brain signals may be more sensitive to real group differences
      than behavioral measures, and (3) patients may achieve comparable levels of
      performance to control subjects by employing alternative or compensatory neural
      strategies. We consider these explanations in relation to data from causal- and
      reward-learning imaging experiments in first-episode psychosis patients. The
      findings suggest that a combination of these factors may resolve the question of
      why performance is sometimes preserved when brain patterns are disrupted.

PMID- 20154203
TI  - SHIP is required for dendritic cell maturation.
AB  - Although several groups have investigated the role of SHIP in macrophage (M)
      development and function, SHIP's contribution to the generation, maturation, and
      innate immune activation of dendritic cells (DCs) is poorly understood. We show
      herein that SHIP negatively regulates the generation of DCs from bone marrow
      precursors in vitro and in vivo, as illustrated by the enhanced expansion of DCs
      from SHIP(-/-) GM-CSF cultures, as well as increased numbers of DCs in the
      spleens of SHIP-deficient mice. Interestingly, however, these SHIP(-/-) DCs
      display a relatively immature phenotype and secrete substantially lower levels of
      IL-12 after TLR ligand stimulation than wild type DCs. This, in turn, leads to a
      dramatically reduced stimulation of Ag-specific T cell proliferation and Th1 cell
      responses in vitro and in vivo. This immature phenotype of SHIP(-/-) DCs could be
      reversed with the PI3K inhibitors LY294002 and wortmannin, suggesting that SHIP
      promotes DC maturation by reducing the levels of the PI3K second messenger
      phosphatidylinositol-3,4,5-trisphosphate. These results are consistent with SHIP
      being a negative regulator of GM-CSF-derived DC generation but a positive
      regulator of GM-CSF-derived DC maturation and function.

PMID- 20154204
TI  - V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate
      sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenous
      leukemia cells.
AB  - Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine
      kinase, is highly effective against chronic myelogenous leukemia (CML) cells.
      However, because 20-30% of patients affected by CML display either primary or
      secondary resistance to imatinib, intentional activation of Vgamma9Vdelta2 T
      cells by phosphoantigens or by agents that cause their accumulation within cells,
      such as zoledronate, may represent a promising strategy for the design of a novel
      and highly innovative immunotherapy capable to overcome imatinib resistance. In
      this study, we show that Vgamma9Vdelta2 T lymphocytes recognize, trogocytose, and
      efficiently kill imatinib-sensitive and -resistant CML cell lines pretreated with
      zoledronate. Vgamma9Vdelta2 T cell cytotoxicity was largely dependent on the
      granule exocytosis- and partly on TRAIL-mediated pathways, was TCR-mediated, and
      required isoprenoid biosynthesis by zoledronate-treated CML cells. Importantly,
      Vgamma9Vdelta2 T cells from patients with CML can be induced by zoledronate to
      develop antitumor activity against autologous and allogeneic zoledronate-treated
      leukemia cells, both in vitro and when transferred into immunodeficient mice in
      vivo. We conclude that intentional activation of Vgamma9Vdelta2 T cells by
      zoledronate may substantially increase their antileukemia activities and
      represent a novel strategy for CML immunotherapy.

PMID- 20154205
TI  - Differential recruitment of activating and inhibitory Fc gamma RII during
      phagocytosis.
AB  - Human myeloid cells express both activating and inhibitory receptors of the
      FcgammaRII family. FcgammaRIIA mediates processes associated with cell
      activation, including phagocytosis of IgG-opsonized particles, whereas
      coengagement of the inhibitory FcgammaRIIB downregulates such signaling. We
      analyzed the relative recruitment of these two receptors during phagocytosis of
      IgG-coated particles by ts20 Chinese hamster fibroblast cells cotransfected with
      both receptors carrying distinguishable fluorescent protein tags. We found that
      FcgammaRIIA is substantially enriched at sites of particle binding relative to
      its inhibitory counterpart, with a greater than 2-fold increase in the local
      ratio of activating to inhibitory receptor compared with that for the plasma
      membrane as a whole. Experiments with chimeric receptors revealed that the
      preferential enrichment of FcgammaRIIA results from differences between the
      extracellular domains of the receptors, and indicated that the lesser recruitment
      of FcgammaRIIB limits its ability to effectively inhibit FcgammaRIIA-mediated
      phagocytosis. Mutagenesis studies indicated that FcgammaRIIA residues leucine 132
      and phenylalanine 160, which lie in IgG-binding regions of FcgammaRIIA and which
      differ in FcgammaRIIB, both contribute to the local relative enrichment of
      FcgammaRIIA by increasing its affinity for IgG1 relative to that of FcgammaRIIB.
      In human monocytes, engagement of approximately equal amounts of FcgammaRIIB was
      required to substantially inhibit FcgammaRIIA-mediated phagocytosis. These
      results demonstrate that differences in affinity for IgG between activating and
      inhibitory FcgammaR can result in substantial local changes in their relative
      concentrations during phagocytosis, with important functional consequences.

PMID- 20154207
TI  - Splicing of distant peptide fragments occurs in the proteasome by
      transpeptidation and produces the spliced antigenic peptide derived from
      fibroblast growth factor-5.
AB  - Peptide splicing is a newly described mode of production of antigenic peptides
      presented by MHC class I molecules, whereby two noncontiguous fragments of the
      parental protein are joined together after excision of the intervening segment.
      Three spliced peptides have been described. In two cases, splicing involved the
      excision of a short intervening segment of 4 or 6 aa and was shown to occur in
      the proteasome by transpeptidation resulting from the nucleophilic attack of an
      acyl-enzyme intermediate by the N terminus of the other peptide fragment. For the
      third peptide, which is derived from fibroblast growth factor-5 (FGF-5), the
      splicing mechanism remains unknown. In this case, the intervening segment is 40
      aa long. This much greater length made the transpeptidation model more difficult
      to envision. Therefore, we evaluated the role of the proteasome in the splicing
      of this peptide. We observed that the spliced FGF-5 peptide was produced in vitro
      after incubation of proteasomes with a 49-aa-long precursor peptide. We evaluated
      the catalytic mechanism by incubating proteasomes with various precursor
      peptides. The results confirmed the transpeptidation model of splicing. By
      transfecting a series of mutant FGF-5 constructs, we observed that reducing the
      length of the intervening segment increased the production of the spliced
      peptide, as predicted by the transpeptidation model. Finally, we observed that
      trans-splicing (i.e., splicing of fragments from two distinct proteins) can occur
      in the cell, but with a much lower efficacy than splicing of fragments from the
      same protein.

PMID- 20154206
TI  - Characterizing the dynamics of CD4+ T cell priming within a lymph node.
AB  - Generating adaptive immunity postinfection or immunization requires physical
      interaction within a lymph node T zone between Ag-bearing dendritic cells (DCs)
      and rare cognate T cells. Many fundamental questions remain regarding the
      dynamics of DC-CD4+ T cell interactions leading to priming. For example, it is
      not known how the production of primed CD4+ T cells relates to the numbers of
      cognate T cells, Ag-bearing DCs, or peptide-MHCII level on the DC. To address
      these questions, we developed an agent-based model of a lymph node to examine the
      relationships among cognate T cell frequency, DC density, parameters
      characterizing DC-T cell interactions, and the output of primed T cells. We found
      that the output of primed CD4+ T cells is linearly related to cognate frequency,
      but nonlinearly related to the number of Ag-bearing DCs present during infection.
      This addresses the applicability of two photon microscopy studies to
      understanding actual infection dynamics, because these types of experiments
      increase the cognate frequency by orders of magnitude compared with physiologic
      levels. We found a trade-off between the quantity of peptide-major
      histocompatibility class II on the surface of individual DCs and number of Ag
      bearing DCs present in the lymph node in contributing to the production of primed
      CD4+ T cells. Interestingly, peptide-major histocompatibility class II t(1/2)
      plays a minor, although still significant, role in determining CD4+ T cell
      priming, unlike the primary role that has been suggested for CD8+ T cell priming.
      Finally, we identify several pathogen-targeted mechanisms that, if altered in
      their efficiency, can significantly effect the generation of primed CD4+ T cells.

PMID- 20154208
TI  - Small-molecule inhibitors of vascular adhesion protein-1 reduce the accumulation
      of myeloid cells into tumors and attenuate tumor growth in mice.
AB  - Vascular adhesion protein-1 (VAP-1) is an endothelial, cell surface-expressed
      oxidase involved in leukocyte traffic. The adhesive function of VAP-1 can be
      blocked by anti-VAP-1 Abs and small-molecule inhibitors. However, the effects of
      VAP-1 blockade on antitumor immunity and tumor progression are unknown. In this
      paper, we used anti-VAP-1 mAbs and small-molecule inhibitors of VAP-1 in B16
      melanoma and EL-4 lymphoma tumor models in C57BL/6 mice. Leukocyte accumulation
      into tumors and neoangiogenesis were evaluated by immunohistochemistry, flow
      cytometry, and intravital videomicroscopy. We found that both anti-VAP-1 Abs and
      VAP-1 inhibitors reduced the number of leukocytes in the tumors, but they
      targeted partially different leukocyte subpopulations. Anti-VAP-1 Abs selectively
      inhibited infiltration of CD8-positive lymphocytes into tumors and had no effect
      on accumulation of myeloid cells into tumors. In contrast, the VAP-1 inhibitors
      significantly reduced only the number of proangiogenic Gr-1(+)CD11b(+) myeloid
      cells in melanomas and lymphomas. Blocking of VAP-1 by either means left tumor
      homing of regulatory T cells and type 2 immune-suppressing monocytes/macrophages
      intact. Notably, VAP-1 inhibitors, but not anti-VAP-1 Abs, retarded the growth of
      melanomas and lymphomas and reduced tumor neoangiogenesis. The VAP-1 inhibitors
      also reduced the binding of Gr-1(+) myeloid cells to the tumor vasculature. We
      conclude that tumors use the catalytic activity of VAP-1 to recruit myeloid cells
      into tumors and to support tumor progression. Small-molecule VAP-1 inhibitors
      therefore might be a potential new tool for immunotherapy of tumors.

PMID- 20154209
TI  - The p110 delta isoform of phosphatidylinositol 3-kinase controls the quality of
      secondary anti-Leishmania immunity by regulating expansion and effector function
      of memory T cell subsets.
AB  - We showed previously that mice with an inactivating knockin mutation in the
      p110delta isoform of PI3K (referred to as p110delta(D910A) mice) displayed
      enhanced primary resistance to Leishmania major despite mounting paradoxically
      impaired T cell responses. In this study, we show that p110delta(D910A) mice are
      impaired in their secondary (memory) anti-Leishmania responses in vitro and in
      vivo. Following secondary L. major challenge, p110delta(D910A) mice exhibited
      reduced delayed-type hypersensitivity response and weaker parasite control
      compared to wild-type mice. Using adoptive transfer experiments, we show that
      immune T cells from healed p110delta(D910A) mice were impaired in their
      proliferation and effector cytokine (IFN-gamma) responses upon L. major
      challenge. Interestingly, Leishmania-reactive T cells from healed
      p110delta(D910A) mice contain severalfold lower numbers of CD62L(lo) and CD62(hi)
      T cells than those from healed wild-type mice. The reduction in numbers of
      CD62L(lo) T cells in p110delta(D910A) mice is due to failure of their CD62L(hi) T
      cells to downregulate CD62L expression in response to L. major. Furthermore,
      although CD62L(lo) cells from p110delta(D910A) mice could home efficiently to
      lymphoid organs, their ability to exit these tissues and emigrate to cutaneous
      sites of infection was greatly impaired. Collectively, our data identify PI3K
      signaling as important events that control memory T cell subset differentiation,
      generation, effector function, and recruitment to cutaneous tissues and suggest
      that manipulating this pathway could provide means of enhancing desired memory T
      cell subset, response during vaccination, or both.

PMID- 20154210
TI  - Essential role of mitochondrial antiviral signaling, IFN regulatory factor
      (IRF)3, and IRF7 in Chlamydophila pneumoniae-mediated IFN-beta response and
      control of bacterial replication in human endothelial cells.
AB  - Chlamydophila pneumoniae infection of the vascular wall as well as activation of
      the transcription factor IFN regulatory factor (IRF)3 have been linked to
      development of chronic vascular lesions and atherosclerosis. The innate immune
      system detects invading pathogens by use of pattern recognition receptors, some
      of which are able to stimulate IRF3/7 activation and subsequent type I IFN
      production (e. g., IFN-beta). In this study, we show that infection of human
      endothelial cells with C. pneumoniae-induced production of IFN-beta, a cytokine
      that so far has been mainly associated with antiviral immunity. Moreover, C.
      pneumoniae infection led to IRF3 and IRF7 nuclear translocation in HUVECs and RNA
      interference experiments showed that IRF3 and IRF7 as well as the mitochondrial
      antiviral signaling (MAVS) were essential for IFN-beta induction. Finally, C.
      pneumoniae replication was enhanced in endothelial cells in which IRF3, IRF7, or
      MAVS expression was inhibited by small interfering RNA and attenuated by IFN-beta
      treatment. In conclusion, C. pneumoniae infection of endothelial cells activates
      an MAVS-, IRF3-, and IRF7-dependent signaling, which controls bacterial growth
      and might modulate development of vascular lesions.

PMID- 20154211
TI  - Lineage-specific combinatorial action of enhancers regulates mouse erythroid
      Gata1 expression.
AB  - Precise spatiotemporal control of Gata1 expression is required in both early
      hematopoietic progenitors to determine erythroid/megakaryocyte versus
      granulocyte/monocyte lineage output and in the subsequent differentiation of
      erythroid cells and megakaryocytes. An enhancer element upstream of the mouse
      Gata1 IE (1st exon erythroid) promoter, mHS-3.5, can direct both erythroid and
      megakaryocytic expression. However, loss of this element ablates only
      megakaryocytes, implying that an additional element has erythroid specificity.
      Here, we identify a double DNaseI hypersensitive site, mHS-25/6, as having
      erythroid but not megakaryocytic activity in primary cells. It binds an
      activating transcription factor complex in erythroid cells where it also makes
      physical contact with the Gata1 promoter. Deletion of mHS-25/6 or mHS-3.5 in
      embryonic stem cells has only a modest effect on in vitro erythroid
      differentiation, whereas loss of both elements ablates both primitive and
      definitive erythropoiesis with an almost complete loss of Gata1 expression.
      Surprisingly, Gata2 expression was also concomitantly low, suggesting a more
      complex interaction between these 2 factors than currently envisaged. Thus,
      whereas mHS-3.5 alone is sufficient for megakaryocytic development, mHS-3.5 and
      mHS-25/6 collectively regulate erythroid Gata1 expression, demonstrating lineage
      specific differences in Gata1 cis-element use important for development of these
      2 cell types.

PMID- 20154212
TI  - Development of multilineage adult hematopoiesis in the zebrafish with a runx1
      truncation mutation.
AB  - Runx1 is required for the emergence of hematopoietic stem cells (HSCs) from
      hemogenic endothelium during embryogenesis. However, its role in the generation
      and maintenance of HSCs during adult hematopoiesis remains uncertain. Here, we
      present analysis of a zebrafish mutant line carrying a truncation mutation, W84X,
      in runx1. The runx1(W84X/W84X) embryos showed blockage in the initiation of
      definitive hematopoiesis, but some embryos were able to recover from a larval
      "bloodless" phase and develop to fertile adults with multilineage hematopoiesis.
      Using cd41-green fluorescent protein transgenic zebrafish and lineage tracing, we
      demonstrated that the runx1(W84X/W84X) embryos developed cd41(+) HSCs in the
      aorta-gonad-mesonephros region, which later migrated to the kidney, the site of
      adult hematopoiesis. Overall, our data suggest that in zebrafish adult HSCs can
      be formed without an intact runx1.

PMID- 20154213
TI  - Molecular response to treatment redefines all prognostic factors in children and
      adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184
      patients of the AIEOP-BFM ALL 2000 study.
AB  - The Associazione Italiana di Ematologia Oncologia Pediatrica and the Berlin
      Frankfurt-Munster Acute Lymphoblastic Leukemia (AIEOP-BFM ALL 2000) study has for
      the first time introduced standardized quantitative assessment of minimal
      residual disease (MRD) based on immunoglobulin and T-cell receptor gene
      rearrangements as polymerase chain reaction targets (PCR-MRD), at 2 time points
      (TPs), to stratify patients in a large prospective study. Patients with precursor
      B (pB) ALL (n = 3184) were considered MRD standard risk (MRD-SR) if MRD was
      already negative at day 33 (analyzed by 2 markers, with a sensitivity of at least
      10(-4)); MRD high risk (MRD-HR) if 10(-3) or more at day 78 and MRD intermediate
      risk (MRD-IR): others. MRD-SR patients were 42% (1348): 5-year event-free
      survival (EFS, standard error) is 92.3% (0.9). Fifty-two percent (1647) were MRD
      IR: EFS 77.6% (1.3). Six percent of patients (189) were MRD-HR: EFS 50.1% (4.1; P
      < .001). PCR-MRD discriminated prognosis even on top of white blood cell count,
      age, early response to prednisone, and genotype. MRD response detected by
      sensitive quantitative PCR at 2 predefined TPs is highly predictive for relapse
      in childhood pB-ALL. The study is registered at http://clinicaltrials.gov:
      NCT00430118 for BFM and NCT00613457 for AIEOP.

PMID- 20154214
TI  - Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization,
      secondary mediators, and Rac.
AB  - The C-type lectin-like receptor 2 (CLEC-2) activates platelets through Src and
      Syk tyrosine kinases via a single cytoplasmic YxxL motif known as a hem
      immunoreceptor tyrosine-based activation motif (hemITAM). Here, we demonstrate
      using sucrose gradient ultracentrifugation and methyl-beta-cyclodextrin treatment
      that CLEC-2 translocates to lipid rafts upon ligand engagement and that
      translocation is essential for hemITAM phosphorylation and signal initiation.
      HemITAM phosphorylation, but not translocation, is also critically dependent on
      actin polymerization, Rac1 activation, and release of ADP and thromboxane A(2)
      (TxA(2)). The role of ADP and TxA(2) in mediating phosphorylation is dependent on
      ligand engagement and rac activation but is independent of platelet aggregation.
      In contrast, tyrosine phosphorylation of the GPVI-FcRgamma-chain ITAM, which has
      2 YxxL motifs, is independent of actin polymerization and secondary mediators.
      These results reveal a unique series of proximal events in CLEC-2 phosphorylation
      involving actin polymerization, secondary mediators, and Rac activation.

PMID- 20154215
TI  - Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a
      mediator of tip cell morphology and branching.
AB  - The development of the vertebrate vascular system is mediated by both genetic
      patterning of vessels and by angiogenic sprouting in response to hypoxia. Both of
      these processes depend on the detection of environmental guidance cues by
      endothelial cells. A specialized subtype of endothelial cell known as the tip
      cell is thought to be involved in the detection and response to these cues, but
      the molecular signaling pathways used by tip cells to mediate tissue
      vascularization remain largely uncharacterized. To identify genes critical to tip
      cell function, we have developed a method to isolate them using laser capture
      microdissection, permitting comparison of RNA extracted from endothelial tip
      cells with that of endothelial stalk cells using microarray analysis. Genes
      enriched in tip cells include ESM-1, angiopoietin-2, and SLP-76. CXCR4, a
      receptor for the chemokine stromal-cell derived factor-1, was also identified as
      a tip cell-enriched gene, and we provide evidence for a novel role for this
      receptor in mediating tip cell morphology and vascular patterning in the neonatal
      retina.

PMID- 20154216
TI  - STAT3 is constitutively phosphorylated on serine 727 residues, binds DNA, and
      activates transcription in CLL cells.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western
      hemisphere, but its pathogenesis is still poorly understood. Constitutive
      tyrosine phosphorylation (p) of signal transducer and activator of transcription
      (STAT) 3 occurs in several solid tumors and hematologic malignancies. In CLL,
      however, STAT3 is constitutively phosphorylated on serine 727, not tyrosine 705,
      residues. Because the biologic significance of serine pSTAT3 in CLL is not known,
      we studied peripheral blood cells of 106 patients with CLL and found that,
      although tyrosine pSTAT3 was inducible, serine pSTAT3 was constitutive in all
      patients studied, regardless of blood count, disease stage, or treatment status.
      In addition, we demonstrated that constitutive serine pSTAT3 translocates to the
      nucleus by the karyopherin-beta nucleocytoplasmic system and binds DNA.
      Dephosphorylation of inducible tyrosine pSTAT3 did not affect STAT3-DNA binding,
      suggesting that constitutive serine pSTAT3 binds DNA. Furthermore, infection of
      CLL cells with lentiviral STAT3-small hairpin RNA reduced the expression of
      several STAT3-regulated survival and proliferation genes and induced apoptosis,
      suggesting that constitutive serine pSTAT3 initiates transcription in CLL cells.
      Taken together, our data suggest that constitutive phosphorylation of STAT3 on
      serine 727 residues is a hallmark of CLL and that STAT3 be considered a
      therapeutic target in this disease.

PMID- 20154217
TI  - Efficacy of the JAK2 inhibitor INCB16562 in a murine model of MPLW515L-induced
      thrombocytosis and myelofibrosis.
AB  - The discovery of JAK2 and MPL mutations in patients with myeloproliferative
      neoplasms (MPNs) provided important insight into the genetic basis of these
      disorders and led to the development of JAK2 kinase inhibitors for MPN therapy.
      Although recent studies have shown that JAK2 kinase inhibitors demonstrate
      efficacy in a JAK2V617F murine bone marrow transplantation model, the effects of
      JAK2 inhibitors on MPLW515L-mediated myeloproliferation have not been
      investigated. In this report, we describe the in vitro and in vivo effects of
      INCB16562, a small-molecule JAK2 inhibitor. INCB16562 inhibited proliferation and
      signaling in cell lines transformed by JAK2 and MPL mutations. Compared with
      vehicle treatment, INCB16562 treatment improved survival, normalized white blood
      cell counts and platelet counts, and markedly reduced extramedullary
      hematopoeisis and bone marrow fibrosis. We observed inhibition of STAT3 and STAT5
      phosphorylation in vivo consistent with potent inhibition of JAK-STAT signaling.
      These data suggest JAK2 inhibitor therapy may be of value in the treatment of
      JAK2V617F-negative MPNs. However, we did not observe a decrease in the size of
      the malignant clone in the bone marrow of treated mice at the end of therapy,
      which suggests that JAK2 inhibitor therapy, by itself, was not curative in this
      MPN model.

PMID- 20154218
TI  - Impact of interactions of cellular components of the bone marrow microenvironment
      on hematopoietic stem and progenitor cell function.
AB  - Hematopoietic stem (HSC) and progenitor (HPC) cell fate is governed by intrinsic
      and extrinsic parameters. We examined the impact of hematopoietic niche elements
      on HSC and HPC function by analyzing the combined effect of osteoblasts (OBs) and
      stromal cells (SCs) on Lineage(-)Sca-1(+)CD117(+) (LSK) cells. CFU expansion and
      marrow repopulating potential of cultured Lineage(-)Sca-1(+)CD117(+) cells were
      significantly higher in OB compared with SC cultures, thus corroborating the
      importance of OBs in the competence of the hematopoietic niche. OB-mediated
      enhancement of HSC and HPC function was reduced in cocultures of OBs and SCs,
      suggesting that SCs suppressed the OB-mediated hematopoiesis-enhancing activity.
      Although the suppressive effect of SC was mediated by adipocytes, probably
      through up-regulation of neuropilin-1, the OB-mediated enhanced hematopoiesis
      function was elaborated through Notch signaling. Expression of Notch 2, Jagged 1
      and 2, Delta 1 and 4, Hes 1 and 5, and Deltex was increased in OB cultures and
      suppressed in SC and OB/SC cultures. Phenotypic fractionation of OBs did not
      segregate the hematopoiesis-enhancing activity but demonstrated that this
      function is common to OBs from different anatomic sites. These data illustrate
      that OBs promote in vitro maintenance of hematopoietic functions, including
      repopulating potential by up-regulating Notch-mediated signaling between HSCs and
      OBs.

PMID- 20154219
TI  - CLEC-2 activates Syk through dimerization.
AB  - The C-type lectin receptor CLEC-2 activates platelets through Src and Syk
      tyrosine kinases, leading to tyrosine phosphorylation of downstream adapter
      proteins and effector enzymes, including phospholipase-C gamma2. Signaling is
      initiated through phosphorylation of a single conserved tyrosine located in a
      YxxL sequence in the CLEC-2 cytosolic tail. The signaling pathway used by CLEC-2
      shares many similarities with that used by receptors that have 1 or more copies
      of an immunoreceptor tyrosine-based activation motif, defined by the sequence
      Yxx(L/I)x(6-12)Yxx(L/I), in their cytosolic tails or associated receptor chains.
      Phosphorylation of the conserved immunoreceptor tyrosine-based activation motif
      tyrosines promotes Syk binding and activation through binding of the Syk tandem
      SH2 domains. In this report, we present evidence using peptide pull-down studies,
      surface plasmon resonance, quantitative Western blotting, tryptophan fluorescence
      measurements, and competition experiments that Syk activation by CLEC-2 is
      mediated by the cross-linking through the tandem SH2 domains with a stoichiometry
      of 2:1. In support of this model, cross-linking and electron microscopy
      demonstrate that CLEC-2 is present as a dimer in resting platelets and converted
      to larger complexes on activation. This is a unique mode of activation of Syk by
      a single YxxL-containing receptor.

PMID- 20154220
TI  - Cyclophosphamide enhances immunity by modulating the balance of dendritic cell
      subsets in lymphoid organs.
AB  - Cyclophosphamide (CTX), a commonly used chemotherapeutic agent can enhance immune
      responses. The ability of CTX to promote the proliferation of effector T cells
      and abrogate the function of regulatory T cells (Tregs) has been described. In
      this study, we examined the effects of CTX treatment on dendritic cell (DC)
      subsets and the subsequent outcome on the effector and suppressive arms of
      adaptive immunity. In secondary lymphoid tissues, tissue-derived migratory DCs
      (migratory DCs), lymphoid tissue-resident DCs (resident DCs), and plasmacytoid
      DCs (pDCs) are well described. CTX has profound and selective cytotoxic effects
      on CD8(+) resident DCs, but not skin-derived migratory DCs or pDCs in lymph nodes
      (LNs) and spleen, causing an imbalance among these DC subsets. CTX treatment
      increases the potency of DCs in antigen presentation and cytokine secretion, and
      partially inhibits the suppressor activity of Tregs. Adoptive transfer of CD8(+)
      DCs can reconstitute this population in regional draining LNs and abrogate the
      immune-enhancing effects of CTX in vivo. These findings demonstrate that CTX may
      improve immune responses by preferentially depleting CD8(+) lymphoid-resident
      DCs, which leads to diminished Treg suppression and enhanced effector T-cell
      function in vivo.

PMID- 20154221
TI  - Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome.
AB  - Trisomy of human chromosome 21 (Hsa21) results in Down syndrome (DS), a disorder
      that affects many aspects of physiology, including hematopoiesis. DS children
      have greatly increased rates of acute lymphoblastic leukemia and acute
      megakaryoblastic leukemia (AMKL); DS newborns present with transient
      myeloproliferative disorder (TMD), a preleukemic form of AMKL. TMD and DS-AMKL
      almost always carry an acquired mutation in GATA1 resulting in exclusive
      synthesis of a truncated protein (GATA1s), suggesting that both trisomy 21 and
      GATA1 mutations are required for leukemogenesis. To gain further understanding of
      how Hsa21 contributes to hematopoietic abnormalities, we examined the Tc1 mouse
      model of DS, which carries an almost complete freely segregating copy of Hsa21,
      and is the most complete model of DS available. We show that although Tc1 mice do
      not develop leukemia, they have macrocytic anemia and increased extramedullary
      hematopoiesis. Introduction of GATA1s into Tc1 mice resulted in a synergistic
      increase in megakaryopoiesis, but did not result in leukemia or a TMD-like
      phenotype, demonstrating that GATA1s and trisomy of approximately 80% of Hsa21
      perturb megakaryopoiesis but are insufficient to induce leukemia.

PMID- 20154222
TI  - Root secretion of phytochemicals in Arabidopsis is predominantly not influenced
      by diurnal rhythms.
AB  - Root-secreted phytochemicals mediate multiple interactions in the rhizosphere.
      The root exudation process can be altered by various biotic factors, including
      pathogenic and non-pathogenic microbes, and abiotic factors like temperature and
      soil moisture. It has been suggested that root secretion of specific flavonoids
      is influenced by diurnal rhythms (by light or dark) but a comprehensive analysis
      of the overall secretion of phytochemicals in response to diurnal rhythms has not
      been studied. In this study, we analyzed the effect of light/dark cycles on root
      exudation profiles using Arabidopsis as a model plant. Our results reveal that
      the root secretion of phytochemicals is partly regulated by the diurnal light
      cycle and follows two main patterns of secretion: (1) the large majority of
      phytochemicals in the exudates showed no diurnal pattern in their secretion, and
      (2) a few compounds showed a diurnal pattern in their secretion: three compounds
      increased in secretion only under light; two compounds increased in secretion
      only while it was dark; and two compounds increased in secretion during the
      transition from dark to light. Root-specific ABC transporters have been
      implicated in root exudation; an analysis of the gene expression patterns of ABC
      transporters in the roots of Arabidopsis at specific time points revealed that
      none of the ABC transporters followed a diurnal expression pattern, suggesting
      that they are expressed constantly during the day and night. Similarly, we
      analyzed the expression in roots of genes involved in secondary metabolite
      biosynthesis and found that some of the genes involved in phenylpropanoid and
      glucosinolate biosynthesis (i.e. 4-coumarate-CoA ligases (4CL1 and 4CL2),
      flavonol synthases (FS1 and FS2), and CYP79B3) followed distinct diurnal
      expression patterns. Overall, we have discovered that while root exudation of the
      majority of phytochemicals is constitutive, the secretion of a few compounds
      follows a diurnal rhythm, which is in accordance with the expression of some
      genes involved in secondary metabolism.

PMID- 20154223
TI  - Induction of human beta-defensin-2 in pulmonary epithelial cells by Legionella
      pneumophila: involvement of TLR2 and TLR5, p38 MAPK, JNK, NF-kappaB, and AP-1.
AB  - Legionella pneumophila is an important causative agent of severe pneumonia in
      humans. Human alveolar epithelium is an effective barrier for inhaled
      microorganisms and actively participates in the initiation of innate host
      defense. Induction of antimicrobial peptide human beta-defensin-2 (hBD-2) by
      various stimuli in epithelial cells has been reported. However, the mechanisms by
      which bacterial infections enhance hBD-2 expression remain poorly understood. In
      this study, we investigated the effect of the pulmonary pathogen L. pneumophila
      on induction of hBD-2 in human pulmonary epithelial cells. Infection with L.
      pneumophila markedly increased hBD-2 production, and the response was attenuated
      in Toll-like receptor (TLR) 2 and TLR5 transient knockdown cells. Furthermore,
      pretreatment with SB-202190 (an inhibitor of p38 MAPK) and JNK II (an inhibitor
      of c-Jun NH(2)-terminal kinase), but not U0126 (an inhibitor of ERK), reduced L.
      pneumophila-induced hBD-2 release in A549 cells. L. pneumophila-induced hBD-2
      liberation was mediated via recruitment of NF-kappaB and AP-1 to the hBD-2 gene
      promoter. Additionally, we showed that exo- and endogenous hBD-2 elicited a
      strong antimicrobial effect towards L. pneumophila. Together, these results
      suggest that L. pneumophila induces hBD-2 release in A549 cells, and the
      induction seems to be mediated through TLR2 and TLR5 as well as activation of p38
      MAPK, JNK, NF-kappaB, and AP-1.

PMID- 20154224
TI  - Bleomycin induces the extrinsic apoptotic pathway in pulmonary endothelial cells.
AB  - Bleomycin, a chemotherapeutic agent, can cause pulmonary fibrosis in humans and
      is commonly used to induce experimental pulmonary fibrosis in rodents. In cell
      culture, bleomycin causes single- and double-stranded DNA breaks and produces
      reactive oxidative species, both of which require iron (Fe(2+)) and O(2). The
      mechanism of bleomycin-induced apoptosis is controversial due to its complexity.
      We investigated bleomycin apoptotic signaling events in primary pulmonary
      endothelial cells. Time course experiments revealed that bleomycin induced
      apoptosis within 4 h. Caspase-8, the initiator caspase for the extrinsic pathway,
      was activated within 2 h and preceded activation of the effector caspases-3 and 
      6 (4 h). Caspase-9, the initiator of the intrinsic pathway and release of
      cytochrome c from the mitochondria were not detected at these time points.
      Bleomycin induced the expression of Bcl-2 and Bcl-x(L), Bcl-2 family member
      proteins that protect cells from the mitochondria-dependent intrinsic apoptosis.
      Real-time quantitative RT-PCR results demonstrated that, at 4-8 h, bleomycin
      induced expression of TNF and TNF receptor family genes known to induce the
      extrinsic apoptotic pathway. Silencing of the death receptor adaptor protein Fas
      associated death domain by short interfering RNA significantly reduced bleomycin
      induced apoptosis. Apoptosis was also abrogated by caspase-8 inhibition, but only
      slightly reduced by caspase-3 inhibition. Together, these data suggest that
      bleomycin initiates apoptosis via the extrinsic pathway.

PMID- 20154225
TI  - Reactivity of mouse alveolar macrophages to cigarette smoke is strain dependent.
AB  - Cigarette smoke (CS) is a main risk factor in chronic obstructive pulmonary
      disease (COPD), but only 20% of smokers develop COPD, suggesting genetic
      predisposition. Animal studies have shown that C57BL/6J mice are sensitive to CS
      and develop emphysema, whereas Institute of Cancer Research (ICR) mice are not.
      To investigate the potential factors responsible for the different susceptibility
      of ICR and C57BL/6J mice to CS, we evaluated in alveolar macrophages (AMs)
      isolated from these strains of mice the possible mechanisms involved in the
      inflammatory and oxidative responses induced by CS. Lactate dehydrogenase (LDH)
      release revealed that C57BL/6J AMs were more susceptible to CS extract (CSE)
      toxicity than ICR. Differences were observed in inflammatory and oxidative
      response after CSE exposure. Proinflammatory cytokines and matrix
      metalloproteinases (MMPs) were increased in C57BL/6J but not ICR AMs. Control
      C57BL/6J AMs showed a higher baseline production of reactive oxygen species (ROS)
      and H(2)O(2) with lower baseline levels of GSH, nuclear factor erythroid 2
      related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase
      (GPX2). This was associated with reduced histone deacetylase-2 (HDAC2)
      expression, activation of NF-kappaB, and higher basal levels of TNF-alpha and IL
      6. CSE induced a decrease in HDAC2 protein levels in both C57BL/6J and ICR AMs;
      however, the level of HDAC2 was significantly lower in C57BL/6 than in ICR AMs.
      Furthermore, CSE enhanced NF-kappaB-dependent cytokine release only in C57BL/6J
      AMs. We suggest that an imbalance in oxidative stress decreases HDAC2 levels and
      facilitates NF-kappaB binding, resulting in a proinflammatory response in
      C57BL/6J but not in ICR AMs. These results could contribute in understanding the
      different susceptibility to CS of these strains of mice.

PMID- 20154232
TI  - Functional impairment in chronic fatigue syndrome, fibromyalgia, and multiple
      chemical sensitivity.
AB  - OBJECTIVE: To characterize patients diagnosed with multiple chemical sensitivity
      (MCS), chronic fatigue syndrome (CFS), or fibromyalgia (FM), to compare their
      level of function with Canadian population average values, and to assess factors
      associated with function. DESIGN: Chart review and abstraction of clinical
      information. SETTING: The Environmental Health Clinic (EHC) at Women's College
      Hospital in Toronto, Ont, which is a provincial referral centre for patients with
      illnesses with suspected environmental links, especially MCS, CFS, and FM.
      PARTICIPANTS: A total of 128 consecutive patients diagnosed with 1 or more of
      MCS, CFS, or FM, seen between January 2005 and March 2006 at the EHC. MAIN
      OUTCOME MEASURES: Demographic and socioeconomic characteristics, comorbid
      diagnoses, duration of illness, health services usage, life stresses, helpful
      therapeutic strategies, and functional impairment measured by the Short Form-36,
      compared with Canadian population average values. Factors significantly
      associated with function in bivariate analyses were included in multiple linear
      and logistic regression models. RESULTS: The patient population was predominantly
      female (86.7%), with a mean age of 44.6 years. Seventy-eight patients had
      discrete diagnoses of 1 of MCS, CFS, or FM, while the remainder had 2 or 3
      overlapping diagnoses. Most (68.8%) had stopped work, and on average this had
      occurred 3 years after symptom onset. On every Short Form-36 subscale, patients
      had markedly lower functional scores than population average values, more so when
      they had 2 or 3 of these diagnoses. Having FM, younger age at onset, and lower
      socioeconomic status were most consistently associated with poor function.
      CONCLUSION: Patients seen at the EHC demonstrated marked functional impairment,
      consistent with their reported difficulties working and caring for their homes
      and families during what should be their peak productive years. Early
      comprehensive assessment, medical management, and social and financial support
      might avoid the deterioration of function associated with prolonged illness.
      Education and information resources are required for health care professionals
      and the public, along with further etiologic and prognostic research.

PMID- 20154226
TI  - In vivo role of leukocyte ADAM17 in the inflammatory and host responses during E.
      coli-mediated peritonitis.
AB  - Inflammation is the body's initial response to infection, which is harmful when
      excessive, as exemplified in sepsis inflammatory syndromes. Ectodomain shedding
      by the membrane metalloprotease ADAM17 is an emerging regulator of inflammation,
      as it directs the activity of various inflammatory modulators. At this time,
      however, little is known about the in vivo function of ADAM17. Here, we show that
      ADAM17-deficient leukocytes afforded mice a survival benefit following
      Escherichia coli-mediated peritoneal sepsis, which was associated with a
      reduction in systemic proinflammatory cytokine levels and bacterial burden. A
      more rapid yet transitory neutrophil infiltration into the peritoneal cavity of
      conditional ADAM17 knockout mice was observed when compared with control mice,
      suggesting a mechanism for their enhanced clearance of bacteria. Preventing the
      shedding of L-selectin augments neutrophil recruitment, and we show that L
      selectin shedding by peritoneal neutrophils in conditional ADAM17 knockout mice
      was impaired. Moreover, their peritoneal TNF-alpha levels were markedly lower
      than control mice following E. coli challenge. These events indicate key
      molecular processes involved in the altered time course of neutrophil recruitment
      in conditional ADAM17 knockout mice. Overall, our study provides novel in vivo
      evidence of the instrumental role of ADAM17 in modulating inflammation and host
      resistance during Gram-negative bacterial infection.

PMID- 20154233
TI  - Nipissing District Developmental Screen: patterns of use by physicians in
      Ontario.
AB  - OBJECTIVE: To determine if providing the Nipissing District Developmental Screen
      (NDDS) free of charge is associated with increased use of this measure and to
      investigate regional variations in the use of the NDDS in Ontario. DESIGN:
      Retrospective analysis of purchasing data from before the NDDS was available at
      no cost compared with analysis of the results of a brief questionnaire completed
      by those downloading the NDDS for free. SETTING: Ontario. PARTICIPANTS: Users of
      the NDDS. INTERVENTION: Provision of free on-line access to the NDDS. MAIN
      OUTCOME MEASURES: Patterns of purchasing or downloading of the NDDS by FPs and
      health care professionals (HCPs) before and after implementation of the program.
      RESULTS: Before the program, 91 FPs (0.9% of FPs in Ontario) purchased the NDDS,
      and an additional 129 FPs (1.3% of FPs in Ontario) downloaded the NDDS in the
      year after the start of the program. Including all other HCPs increased the
      estimated number of users to 504 (representing an estimated 5.0% of all FPs in
      Ontario). Adjusting for group practice increased the estimate to 16.5% of all FPs
      in Ontario who had access to the NDDS. There were no significant differences in
      NDDS usage by FPs between central, southwestern, and northern Ontario (P > .05).
      Significantly fewer FPs in eastern Ontario accessed the NDDS than FPs in other
      areas of the province did (P < .001). CONCLUSION: Despite measures to increase
      usage, only a small number of FPs access the NDDS in Ontario. However, free
      access to the NDDS does seem to contribute to removing barriers to screening, as
      indicated by a 3-fold increase in the number of FPs accessing the NDDS. Further
      research is required to investigate the reasons for these trends so that
      effective methods to increase the use of developmental screening measures in
      clinical practice can be implemented.

PMID- 20154234
TI  - Methods for a study of Anticipatory and Preventive multidisciplinary Team Care in
      a family practice.
AB  - BACKGROUND T o examine the methodology used to evaluate whether focusing the work
      of nurse practitioners and a pharmacist on frail and at-risk patients would
      improve the quality of care for such patients. DESIGN: Evaluation of methodology
      of a randomized controlled trial including analysis of quantitative and
      qualitative data over time and analysis of cost-effectiveness. SETTING: A single
      practice in a rural area near Ottawa, Ont. PARTICIPANTS: A total of 241 frail
      patients, aged 50 years and older, at risk of experiencing adverse health
      outcomes. INTERVENTION: At-risk patients were randomly assigned to receive
      Anticipatory and Preventive Team Care (from their family physicians, 1 of 3 nurse
      practitioners, and a pharmacist) or usual care. MAIN OUTCOME MEASURES: The
      principal outcome for the study was the quality of care for chronic disease
      management. Secondary outcomes included other quality of care measures and
      evaluation of the program process and its cost-effectiveness. This article
      examines the effectiveness of the methodology used. Quantitative data from
      surveys, administrative databases, and medical records were supplemented with
      qualitative information from interviews, focus groups, work logs, and study
      notes. CONCLUSION: Three factors limit our ability to fully demonstrate the
      potential effects of this team structure. For reasons outside our control, the
      intervention duration was shorter than intended; the practice's physical layout
      did not facilitate interactions between the care providers; and contamination of
      the intervention effect into the control arm cannot be excluded. The study used a
      randomized design, relied on a multifaceted approach to evaluating its effects,
      and used several sources of data. TRIAL REGISTRATION NUMBER NCT00238836
      (CONSORT).

PMID- 20154235
TI  - If only we could predict the future!

PMID- 20154237
TI  - Safety of long-acting beta2-agonists in the management of asthma: a Primary Care
      Respiratory Alliance of Canada perspective.

PMID- 20154239
TI  - Must family physicians use spirometry in managing asthma patients?: YES.

PMID- 20154240
TI  - Must family physicians use spirometry in managing asthma patients?: NO.

PMID- 20154241
TI  - One-sided arguments.

PMID- 20154244
TI  - Treatment of heartburn and acid reflux associated with nausea and vomiting during
      pregnancy.
AB  - QUESTION: In addition to suffering from nausea and vomiting of pregnancy, which
      is being treated with antiemetics, some of my pregnant patients complain of
      heartburn and acid reflux. Should these symptoms also be treated and, if so,
      which acid-reducing medications are safe for use during pregnancy? ANSWER:
      Increased severity of nausea and vomiting of pregnancy is associated with the
      presence of heartburn and acid reflux. Antacids, histamine-2 receptor
      antagonists, and proton pump inhibitors can be used safely during pregnancy, as
      large studies have been published with no evidence of adverse fetal effects.

PMID- 20154243
TI  - Helping patients with localized prostate cancer reach treatment decisions.
AB  - OBJECTIVE: To highlight the role of psychosocial variables in treatment decision
      making for patients with localized prostate cancer and how family physicians can
      be of most help to such patients in facilitating good treatment choices. QUALITY
      OF EVIDENCE: PubMed was searched, and articles relevant to the psychosocial
      aspects of localized prostate cancer treatment decision making were included.
      Articles were excluded when they clearly specified inclusion of men with
      metastatic disease. This is not a systematic review, and recommendations made are
      drawn from studies of level II or III evidence. MAIN MESSAGE: The optimal
      strategy for managing localized prostate cancer has not been established and
      currently includes a number of potential options: active surveillance, radical
      prostatectomy, external beam radiotherapy, brachytherapy, and cryoablation.
      Consequently, men often struggle during the decision-making process, and some
      later regret their decisions. With an increased awareness of the psychosocial
      aspects of patient decision making, family physicians can help patients make
      better decisions. CONCLUSION: Family physicians can help minimize the decisional
      regret experienced by patients after treatment by encouraging patients to
      consider their values and social supports, as well as the accuracy and
      appropriateness of the information used in the decision-making process.

PMID- 20154245
TI  - ADHD stimulants and their effect on height in children.
AB  - QUESTION: Many more children today are diagnosed and treated for attention
      deficit hyperactivity disorder. Parents frequently ask me if the stimulant
      medications their children receive might affect their height as adults. What
      should I tell them? ANSWER: Stimulant medications, including methylphenidate and
      amphetamine, are safe and effective in children and adolescents with attention
      deficit hyperactivity disorder. Research on the issue of growth suppression is
      lacking, mostly owing to insufficient follow-up on patients' final heights. In
      general, the rate of height loss seems relatively small and is likely reversible
      with withdrawal of treatment. Clinical presentation and academic achievements
      should be the key to determining which drug to prescribe, the preparation, and
      the dose.

PMID- 20154246
TI  - Forms for father: military Veteran with unmet health care needs.

PMID- 20154247
TI  - Gastric dilatation as a cause of acute respiratory distress.

PMID- 20154248
TI  - Question: can you identify this condition? Answer: congenital dermal sinus with a
      tethered cord.

PMID- 20154249
TI  - Question: can you identify this condition? Answer: leukocoria.

PMID- 20154252
TI  - Mentoring in medicine.

PMID- 20154251
TI  - Tobacco-related medical education and physician interventions with parents who
      smoke: Survey of Canadian family physicians and pediatricians.
AB  - OBJECTIVE: To examine the relationship between physicians' tobacco-related
      medical training and physicians' confidence in their tobacco-related skills and
      smoking-related interventions with parents of child patients. DESIGN: Mailed
      survey. SETTING: Canada. PARTICIPANTS: The survey was mailed to 800 family
      physicians and 800 pediatricians across Canada, with a corrected response rate of
      65% (N = 900). MAIN OUTCOME MEASURES: Physicians' self-reported tobacco-related
      education, knowledge, and skills, as well as smoking-related interventions with
      parents of child patients. Cochran-Mantel-Haenszel chi(2) tests were used to
      examine relationships between variables, controlling for tobacco-control
      involvement and physician specialty. Data analysis was conducted in 2008.
      RESULTS: Physicians reporting tobacco-related medical education were more likely
      to report being "very confident" in advising parents about the effects of smoking
      and the use of a variety of cessation strategies (P < .05). Furthermore,
      physicians with tobacco-related training were more likely to help parents of
      child patients quit smoking whether or not the children had respiratory problems
      (P < .05). Physicians with continuing medical education in this area were more
      likely to report confidence in their tobacco-related skills and to practise more
      smoking-related interventions than physicians with other forms of training.
      CONCLUSION: There is a strong relationship between medical education and
      physicians' confidence and practices in protecting children from secondhand
      smoke. Physicians with continuing medical education training are more confident
      in their tobacco-related skills and are more likely to practise smoking-related
      interventions than physicians with other tobacco-related training.

PMID- 20154256
TI  - High levels of fatty acids increase contractile function of neonatal rabbit
      hearts during reperfusion following ischemia.
AB  - In the neonatal heart the transition from using carbohydrates to using fatty
      acids has not fully matured and oxidative metabolism/ATP generation may be
      limiting contractile function after ischemia. This study tested the hypothesis
      that increasing fatty acid availability increases recovery of left ventricular
      (LV) work by increasing palmitate oxidation, tricarboxylic acid (TCA) cycle
      activity, and ATP generation. Isolated working hearts from 7-day-old rabbits were
      perfused with Krebs solution containing low (0.4 mM) or high (2.4 mM) palmitate
      and 5.5 mM glucose. Hearts were subjected to 35-min global ischemia before 40-min
      reperfusion, and rates of glycolysis, glucose oxidation, and palmitate oxidation
      were assessed. LV work was similar before ischemia but was greater during
      reperfusion in hearts perfused with 2.4 mM palmitate compared with hearts
      perfused with 0.4 mM palmitate [6.98 +/- 0.14 (n = 15) vs. 3.01 +/- 0.23 (n = 16)
      mJ.beat(-1).g dry wt(-1); P < 0.05]. This was accompanied by increased LV energy
      expenditure during reperfusion [35.98 +/- 0.16 (n = 8) vs. 19.92 +/- 0.18 (n = 6)
      mJ.beat(-1).g dry wt(-1); P < 0.05]. During reperfusion the rates of palmitate
      oxidation [237.5 +/- 28.10 (n = 7) vs. 86.0 +/- 9.7 (n = 6) nmol.g dry wt(
      1).min(-1); P < 0.05], total TCA cycle activity [2.65 +/- 0.39 (n = 7) vs. 1.36
      +/- 0.14 (n = 6) micromol acetyl-CoA.g dry wt(-1).min(-1); P < 0.05], and ATP
      generation attributable to palmitate oxidation [26.6 +/- 3.1 (n = 7) vs. 12.6 +/-
      1.7 (n = 6) micromol.g dry wt(-1).min(-1); P < 0.05] were greater in hearts
      perfused with 2.4 mM palmitate. These data indicate that the neonatal heart has
      decreased energy reserve, and, in contrast to the mature heart, increasing
      availability of fatty acid substrate increases energy production and improves
      recovery of function after ischemia.

PMID- 20154257
TI  - Impact of anti-apoptotic and anti-oxidative effects of bone marrow mesenchymal
      stem cells with transient overexpression of heme oxygenase-1 on myocardial
      ischemia.
AB  - Although mesenchymal stem cells (MSCs) have therapeutic potential for tissue
      injury, intolerance and poor cell viability limit their reparative capability.
      Therefore, we examined the impact of bone marrow-derived MSCs, in which heme
      oxygenase-1 (HO-1) was transiently overexpressed, on the repair of an ischemic
      myocardial injury. When MSCs and HO-1-overexpressed MSCs (MSC(HO-1)) were exposed
      to serum deprivation/hypoxia or H(2)O(2)-induced oxidative stress, MSC(HO-1)
      exhibited increased resistance to cell apoptosis compared with MSCs (17 +/- 1 vs.
      30 +/- 2%, P < 0.05) and were markedly resistant to cell death (2 +/- 1 vs. 32 +/
      2%, P < 0.05). Under these conditions, vascular endothelial growth factor (VEGF)
      production was 2.1-fold greater in MSC(HO-1) than in MSCs. Pretreatment of MSCs
      and MSC(HO-1) with phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B
      (Akt) pathway inhibitors such as LY-294002 (50 muM) or wortmannin (100 nM)
      significantly decreased VEGF production. In a rat infarction model with MSCs or
      MSC(HO-1) (5 x 10(6) +/- 0.1 x 10(6) cells/rat) transplantation, the number of
      TdT-mediated dUTP nick end-labeling-positive cells was significantly lower in the
      MSC(HO-1) group than in the MSC group (12.1 +/- 1.0 cells/field vs. 26.5 +/- 2.6,
      P < 0.05) on the 4th day after cell transplantation. On the 28th day, increased
      capillary density associated with decreased infarction size was observed in the
      MSC(HO-1) group (1,415 +/- 47/mm(2) with 21.6 +/- 2.3%) compared with those in
      the MSCs group (1,215 +/- 43/mm(2) with 28.2 +/- 2.3%, P < 0.05), although
      infarction size relative to area at risk was not different in each group at 24 h
      after transplantation. These results demonstrate that MSC(HO-1) exhibit markedly
      enhanced anti-apoptotic and anti-oxidative capabilities compared with MSCs, thus
      contributing to improved repair of ischemic myocardial injury through cell
      survival and VEGF production associated with the PI 3-kinase/Akt pathway.

PMID- 20154258
TI  - RhoA-Rho kinase signaling mediates endothelium- and endoperoxide-dependent
      contractile activities characteristic of hypertensive vascular dysfunction.
AB  - Hypertensive vasomotor dysfunction is defined by endothelium-dependent
      contractions involving prostaglandins and ROS. Since both thromboxane-prostanoid
      receptor (TPr) signaling and ROS activate RhoA-Rho kinase (ROCK) in vascular
      smooth muscle (VSM) preparations, we hypothesized that enhanced endothelium
      dependent contraction in the common carotid artery (CCA) of spontaneously
      hypertensive rats (SHRs) is ROCK mediated. ACh-stimulated contractions were
      approximately twofold greater in SHRs versus normotensive Wistar-Kyoto (WKY)
      rats, abolished by endothelial denudation or cyclooxygenase (COX)-1 inhibition,
      and nearly eliminated by TPr blockade. RhoA but not ROCK-II protein expression
      was increased ( approximately 50%) in the SHR CCA. Inhibition of ROCK, but not
      protein kinase C, caused a dose-dependent reduction in endothelium-dependent
      contractions to ACh across strains, with the highest dose mirroring the effect of
      high-dose TPr antagonism. Conversely, ROCK inhibition caused dose-dependent and
      endothelium- and nitric oxide-independent relaxation in CCAs precontracted with
      the TPr agonist U-46619. Prostacyclin was the predominant prostaglandin produced
      by ACh-stimulated CCAs, with greater than twofold more prostacyclin released from
      SHR versus WKY rats, and its production was unaffected by ROCK inhibition. RhoA
      activation was approximately twofold higher in quiescent SHR CCAs compared with
      those from WKY rats and was significantly increased by ACh stimulation.
      Augmentation of chemical superoxide quenching with tiron or inhibition of the
      NADPH oxidase-derived superoxide-producing pathway with apocynin reduced ACh
      stimulated contractile activity in SHR more than in WKY rats, whereas the SOD
      mimetic tempol amplified the response. Exposure of CCAs to exogenous H(2)O(2)
      caused contractions, similar to ACh stimulation, that were greater in SHR than in
      WKY rats, abolished by COX-1 inhibition, and highly attenuated by TPr blockade or
      ROCK inhibition. These results indicate that RhoA-ROCK may act as a molecular
      switch, transducing signals from endothelium-derived prostaglandin(s) and ROS,
      which are overproduced in SHR CCAs, to "turn on" VSM contractile pathways, thus
      mediating the enhanced endothelium- and endoperoxide-dependent vascular
      contractions characteristic of hypertension, among other cardiovascular disease
      states, such as diabetes and aging.

PMID- 20154259
TI  - RT variability unrelated to heart period and respiration progressively increases
      during graded head-up tilt.
AB  - Open-loop linear parametric models were exploited to describe ventricular
      repolarization duration (VRD) variability during graded head-up tilt. Surface ECG
      and thoracic movements were recorded in 15 healthy humans (age: 24-54 yr, median:
      28 yr; 6 women and 9 men). Tilt table inclinations ranged from 15 to 90 degrees
      and were varied in steps of 15 degrees . All subjects underwent recordings at
      every step in random order. Heart period was assessed as the time difference
      between two consecutive R-wave peaks (RR) and the respiratory signal (R) as the
      sampling of the thoracic movement signal at the R-wave peaks. VRD was measured
      automatically as the temporal difference between the R-wave peak and T-wave apex
      (RT(a)) or T-wave end (RT(e)). The best model decomposed RT variability as due to
      RR changes (RR-related RT variability) to direct respiratory-related inputs (R
      related RT variability) and to unknown rhythmical sources unrelated to RR changes
      and R (RR-R-unrelated RT variability). Using this model, RT(e) variability was
      found to be less predictable than RT(a) variability and composed of a smaller
      fraction of RR-related RT variability and a larger fraction of RR-R-unrelated RT
      variability. Predictability progressively decreased with tilt table angles,
      suggesting increased complexity of RT regulation. RT variance progressively
      increased with tilt table inclination. This increase was characterized by a
      gradual rise of the amount of RR-R-unrelated RT variability, whereas the amount
      of RR-related RT variability remained unchanged. These results suggest that the
      amount of RT variability, complexity of RT dynamics, and amount of RR-R-unrelated
      RT variability increase with the magnitude of the sympathetic drive directly
      related to tilt table inclination. We propose the utilization of the amount of RR
      R-unrelated RT variability instead of overall RT variability as an indirect
      measure of autonomic regulation directed to ventricles.

PMID- 20154260
TI  - Increased muscle sympathetic nerve activity acutely alters conduit artery shear
      rate patterns.
AB  - Escalating evidence indicates that disturbed flow patterns, characterized by the
      presence of retrograde and oscillatory shear stress, induce a proatherogenic
      endothelial cell phenotype; however, the mechanisms underlying oscillatory shear
      profiles in peripheral conduit arteries are not fully understood. We tested the
      hypothesis that acute elevations in muscle sympathetic nerve activity (MSNA) are
      accompanied by increases in conduit artery retrograde and oscillatory shear.
      Fourteen healthy men (25 +/- 1 yr) performed three sympathoexcitatory maneuvers:
      graded lower body negative pressure (LBNP) from 0 to -40 Torr, cold pressor test
      (CPT), and 35% maximal voluntary contraction handgrip followed by postexercise
      ischemia (PEI). MSNA (microneurography; peroneal nerve), arterial blood pressure
      (finger photoplethysmography), and brachial artery velocity and diameter (duplex
      Doppler ultrasound) in the contralateral arm were recorded continuously. All
      maneuvers elicited significant increases in MSNA total activity from baseline (P
      < 0.05). Retrograde shear (-3.96 +/- 1.2 baseline vs. -8.15 +/- 1.8 s(-1), -40
      LBNP, P < 0.05) and oscillatory shear index (0.09 +/- 0.02 baseline vs. 0.20 +/-
      0.02 arbitrary units, -40 LBNP, P < 0.05) were progressively augmented during
      graded LBNP. In contrast, during CPT and PEI, in which MSNA and blood pressure
      were concomitantly increased (P < 0.05), minimal or no changes in retrograde and
      oscillatory shear were noted. These data suggest that acute elevations in MSNA
      are associated with an increase in conduit artery retrograde and oscillatory
      shear, an effect that may be influenced by concurrent increases in arterial blood
      pressure. Future studies should examine the complex interaction between MSNA,
      arterial blood pressure, and other potential modulatory factors of shear rate
      patterns.

PMID- 20154261
TI  - Novel bradykinin signaling in adult rat cardiac myocytes through activation of
      p21-activated kinase.
AB  - Although bradykinin (BK) is known to exert effects on the myocardium, its
      intracellular signaling pathways remain poorly understood. Experiments in other
      cell types indicated that p21-activated kinase-1 (Pak1), a Ser/Thr kinase
      downstream of small monomeric G proteins, is activated by BK. We previously
      reported that the expression of active Pak1 in adult cardiac myocytes induced
      activation of protein phosphatase 2A and dephosphorylation of myofilament
      proteins (Ke et al. Circ Res 94: 194-200, 2004). In experiments reported here, we
      tested the hypothesis that BK signals altered protein phosphorylation in adult
      rat cardiac myocytes through the activation and translocation of Pak1. Treatment
      of myocytes with BK resulted in the activation of Pak1 as demonstrated by
      increased autophosphorylation at Thr423 and a diminished striated localization,
      which is present in the basal state. BK induced dephosphorylation of both cardiac
      troponin I and phospholamban. Treatment of isolated myocytes with BK also blunted
      the effect of isoproterenol to enhance peak Ca(2+) and relaxation of Ca(2+)
      transients. Protein phosphatase 2A was demonstrated to associate with both Pak 1
      and phospholamban. Our studies indicate a novel signaling mechanism for BK in
      adult rat cardiac myocytes and support our hypothesis that Pak 1 is a significant
      regulator of phosphatase activity in the heart.

PMID- 20154262
TI  - Targeted inhibition of activin receptor-like kinase 5 signaling attenuates
      cardiac dysfunction following myocardial infarction.
AB  - Following myocardial infarction (MI), the heart undergoes a pathological process
      known as remodeling, which in many instances results in cardiac dysfunction and
      ultimately heart failure and death. Transforming growth factor-beta (TGF-beta) is
      a key mediator in the pathogenesis of cardiac remodeling following MI. We thus
      aimed to inhibit TGF-beta signaling using a novel orally active TGF-beta type I
      receptor [activin receptor-like kinase 5 (ALK5)] inhibitor (GW788388) to
      attenuate left ventricular remodeling and cardiac dysfunction in a rat model of
      MI. Sprague-Dawley rats underwent left anterior descending coronary artery
      ligation to induce experimental MI and then were randomized to receive GW788388
      at a dosage of 50 mg.kg(-1).day(-1) or vehicle 1 wk after surgery. After 4 wk of
      treatment, echocardiography was performed before the rats were euthanized.
      Animals that received left anterior descending coronary artery ligation
      demonstrated systolic dysfunction, Smad2 activation, myofibroblasts accumulation,
      collagen deposition, and myocyte hypertrophy (all P < 0.05). Treatment with
      GW788388 significantly attenuated systolic dysfunction in the MI animals,
      together with the attenuation of the activated (phosphorylated) Smad2 (P < 0.01),
      alpha-smooth muscle actin (P < 0.001), and collagen I (P < 0.05) in the
      noninfarct zone of MI rats. Cardiomyocyte hypertrophy in MI hearts was also
      attenuated by ALK5 inhibition (P < 0.05). In brief, treatment with a novel TGF
      beta type I receptor inhibitor, GW788388, significantly reduced TGF-beta
      activity, leading to the attenuation of systolic dysfunction and left ventricular
      remodeling in an experimental rat model of MI.

PMID- 20154263
TI  - Strain-dependent susceptibility for hypertension in mice resides in the natural
      killer gene complex.
AB  - Hypertension is associated with chronic vascular inflammation. We tested the
      hypothesis that the sensitivity to develop hypertension and vascular remodeling
      depends on the immunological background. Blood pressure, vascular remodeling,
      endothelial function, vascular architecture (number of collateral arteries), and
      expression of inflammatory cytokines were determined in mice that received N(G)
      nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthesis. We
      studied C57BL/6, BALB/c, and BALB.B6-Cmv1r mice, a congenic strain where the
      natural killer (NK) gene complex of C57BL/6 mice is introduced in the BALB/c
      background. During a 4-wk treatment with l-NAME, blood pressure initially
      increased in both C57BL/6 and BALB/C mice, but after 4 wk, only C57BL/6 mice
      showed a significant increase in mean arterial blood pressure (+53 mmHg; P <
      0.001) and small artery inward remodeling. Endothelial function and vascular
      design were significantly different between C57BL/6 mice and BALB/C mice. The
      inflammatory response was similar in C57BL/6 and BALB/C mice, except for the
      leukocyte marker CD11b. Cellular colocalization of CD11b with NK1.1 indicated the
      recruitment of NK cells in C57BL/6 mice. Congenic BALB.B6-Cmv1r mice showed the
      same endothelial response and vascular architecture as BALB/c mice. However,
      BALB.B6-Cmv1r mice displayed a similar sensitivity to hypertension and vascular
      remodeling as C57BL/6 mice. In conclusion, we have identified the NK gene complex
      as an important determinant in the genetically determined sensitivity to develop
      l-NAME-induced hypertension in mice.

PMID- 20154264
TI  - Ac-SDKP inhibits transforming growth factor-beta1-induced differentiation of
      human cardiac fibroblasts into myofibroblasts.
AB  - N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits collagen production and
      cell proliferation in cultured rat cardiac fibroblasts, but its effect on
      differentiation of fibroblasts into myofibroblasts is not known. High amounts of
      transforming growth factor-beta1 (TGF-beta1) have been found in fibrotic cardiac
      tissue. TGF-beta1 converts fibroblasts into myofibroblasts, which produce more
      extracellular matrix proteins than fibroblasts. We hypothesized that 1) Ac-SDKP
      inhibits TGF-beta1-induced differentiation of fibroblasts into myofibroblasts;
      and 2) this effect is mediated in part by blocking phosphorylation of small
      mothers-against-decapentaplegic (Smad) 2 and extracellular signal-regulated
      kinase (ERK) 1/2. For this study, we used human fetal cardiac fibroblasts (HCFs),
      which do not spontaneously become myofibroblasts when cultured at low passages.
      We investigated the effect of Ac-SDKP on TGF-beta1-induced HCF transformation
      into myofibroblasts, Smad2 and ERK1/2 phosphorylation, Smad7 expression, cell
      proliferation, and collagen production. We also investigated TGF-beta1 production
      by HCFs stimulated with endothelin-1 (ET-1). As expected, HCFs treated with TGF
      beta1 transformed into myofibroblasts as indicated by increased expression of
      alpha-smooth muscle actin and a higher proportion of the embryonic isoform of
      smooth muscle myosin compared with untreated cells. TGF-beta1 also increased
      Smad2 and ERK1/2 phosphorylation but did not affect Smad7 expression. In
      addition, TGF-beta1 stimulated HCF proliferation as indicated by an increase in
      mitochondrial dehydrogenase activity and collagen production (hydroxyproline
      assay). Ac-SDKP significantly inhibited all of the effects of TGF-beta1. It also
      inhibited ET-1-stimulated TGF-beta1 production. We concluded that Ac-SDKP
      markedly suppresses differentiation of human cardiac fibroblasts into
      myofibroblasts, probably by inhibiting the TGF-beta/Smad/ERK1/2 signaling
      pathway, and thus mediating its anti-fibrotic effects.

PMID- 20154265
TI  - Hydrogen sulfide protects cardiomyocytes from hypoxia/reoxygenation-induced
      apoptosis by preventing GSK-3beta-dependent opening of mPTP.
AB  - Hydrogen sulfide (H(2)S) is an endogenously generated gaseous transmitter, which
      has recently been suggested to regulate cardiovascular functions. The present
      study aims to clarify the mechanisms underlying the cardioprotective effects of
      H(2)S. Signaling elements were examined in cardiomyocytes cultured under
      hypoxia/reoxygenation conditions and in a rat model of ischemia-reperfusion. In
      cultured cardiomyocytes, sodium hydrosulfide (NaHS; 10, 30, and 50 mumol/l)
      showed concentration-dependent inhibitory effects on cardiomyocyte apoptosis
      induced by hypoxia/reoxygenation. These effects were associated with an increase
      in phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) (Ser9) and a
      decrease in Bax translocation, caspase-3 activation, and mitochondrial
      permeability transition pore (mPTP) opening. Transfection of a phosphorylation
      resistant mutant of GSK-3beta at Ser9 attenuated the effects of NaHS in reducing
      cardiomyocyte apoptosis, Bax translocation, caspase-3 activation, and mPTP
      opening. In a rat model of ischemia-reperfusion, NaHS administration reduced
      myocardial infarct size and increased the phosphorylation of GSK-3beta (Ser9) at
      a dose of 30 mumol/kg. In conclusion, the H(2)S donor prevents cardiomyocyte
      apoptosis by inducing phosphorylation of GSK-3beta (Ser9) and subsequent
      inhibition of mPTP opening.

PMID- 20154266
TI  - Human CD4- 8- T cells are a distinctive immunoregulatory subset.
AB  - Human CD4(-)8(-) T cells are a minor subset quantitatively but potentially
      important in immunity because they are predominantly distributed at body
      surfaces, and their number and activities increase in autoimmune diseases and
      decrease with aging. Distinguishing characteristics of CD4(-)8(-) T cells are
      found to include a unique profile of cytokines, including Serpin E1, which is not
      generated by other T cells, MIF, and TGF-beta. At 2-5% of the total in mixtures
      with CD4 + CD8 T cells, CD4(-)8(-) T cells enhance the generation of IFN-gamma
      and IL-17 by up to 12- and 5-fold, respectively, without contributing either
      cytokine or affecting cytokine production by NK/NKT cells. CD4(-)8(-) T cell
      derived MIF is their major enhancer and TGFbeta their principal inhibitor of CD4
      and CD8 T cell cytokine production. Decreases in CD4(-)8(-) T cell effects may
      diminish protective immunity in aging, whereas increases may augment the severity
      of autoimmune diseases.

PMID- 20154267
TI  - Obox4 critically regulates cAMP-dependent meiotic arrest and MI-MII transition in
      oocytes.
AB  - Extra follicular oocytes spontaneously resume meiosis in vitro, but the intact
      germinal vesicle (GV) is retained if the oocytes are cultured in medium
      containing phosphodiesterase (PDE) inhibitors or cAMP analogues. On the basis of
      our finding that Obox4 is prominently expressed in oocytes, the present study was
      conducted to determine the functional role of the homeodomain-containing factor
      Obox4 during in vitro oocyte maturation. After microinjection of Obox4 dsRNA into
      the cytoplasm of GV oocytes cultured in M16 medium, oocytes were arrested at
      metaphase I (MI, 77.7%) and metaphase II (MII, 22.3%). Surprisingly, however, 89%
      of Obox4 RNAi-treated oocytes resumed meiosis and developed to MI and MII when
      cultured in medium containing 0.2 mM 3-isobutyl-1-methyl-xanthine (IBMX), in
      which untreated oocytes maintain intact GVs. Spindles were aberrant, and
      chromosomes were severely aggregated with decreased MPF and MAP kinase activities
      in arrested MI oocytes after exposure to Obox4 RNAi. Oocytes overexpressing Obox4
      retained intact GVs when cultured in M16 medium. Taken together, for the first
      time to our knowledge, these findings indicate that Obox4 plays a key role in the
      cAMP-dependent signaling cascades that maintain GV arrest. Oocytes not expressing
      Obox4 failed to maintain intact GVs in IBMX-supplemented medium, while GVs
      remained intact when oocytes were kept in plain medium and overexpressing Obox4,
      suggesting that Obox4 plays a critical role in cAMP-dependent cascade for
      maintaining intact GVs.

PMID- 20154268
TI  - Proteinase-activated receptor-2 up-regulation by Fcgamma-receptor activation in
      human neutrophils.
AB  - We shed new light on the expression and function of the proteinase-activated
      receptor (PAR) family, associated with inflammation and hyperalgesia, in human
      granulocytes. Resting cells expressed constitutive levels of PAR-2 and PAR-3 mRNA
      but not PAR-1 or PAR-4. Based on flow cytometry, stimulation with opsonized
      bacteria (Bop) specifically up-regulated cell surface expression of PAR-2 in a
      concentration-dependent and time-dependent manner, independent of transcription
      or de novo protein synthesis. Primary granules were identified as a source of
      preformed PAR-2 that can readily be mobilized at the surface on fusion with the
      plasma membrane. Cellular response to PAR-2 activation, measured as changes in
      intracellular calcium concentration, was enhanced in PAR-2 up-regulated cells.
      Increase of cell-surface PAR-2 and of cell responsiveness were dependent
      specifically on the engagement of immunoglobulin (Ig)-binding receptors.
      Together, our results reveal that mobilization of intracellular granules, in
      response to Ig-receptor activation, up-regulates PAR-2 surface expression and
      makes neutrophils more responsive to proteinase activity. This enhanced response
      to PAR-2 activation indicates that molecular communication between pain and
      inflammation may be more important than previously believed.

PMID- 20154269
TI  - BCL2 and CASP8 regulation by NF-kappaB differentially affect mitochondrial
      function and cell fate in antiestrogen-sensitive and -resistant breast cancer
      cells.
AB  - Resistance to endocrine therapies remains a major problem in the management of
      estrogen receptor-alpha (ER)-positive breast cancer. We show that inhibition of
      NF-kappaB (p65/RELA), either by overexpression of a mutant IkappaB (IkappaBSR) or
      a small-molecule inhibitor of NF-kappaB (parthenolide; IC(50)=500 nM in tamoxifen
      resistant cells), synergistically restores sensitivity to 4-hydroxytamoxifen
      (4HT) in resistant MCF7/RR and MCF7/LCC9 cells and further sensitizes MCF-7 and
      MCF7/LCC1 control cells to 4HT. These effects are independent of changes in
      either cell cycle distribution or in the level of autophagy measured by
      inhibition of p62/SQSTM1 expression and cleavage of LC3. NF-kappaB inhibition
      restores the ability of 4HT to decrease BCL2 expression, increase mitochondrial
      membrane permeability, and induce a caspase-dependent apoptotic cell death in
      resistant cells. Each of these effects is reversed by a caspase 8 (CASP8)
      specific inhibitor that blocks enzyme-substrate binding. Thus, increased
      activation of NF-kappaB can alter sensitivity to tamoxifen by modulating CASP8
      activity, with consequent effects on BCL2 expression, mitochondrial function, and
      apoptosis. These data provide significant new insights into how molecular
      signaling affects antiestrogen responsiveness and strongly suggest that a
      combination of parthenolide and tamoxifen may offer a novel therapeutic approach
      to the management of some ER-positive breast cancers.

PMID- 20154270
TI  - Two isoforms of human RNA polymerase III with specific functions in cell growth
      and transformation.
AB  - Transcription in eukaryotic nuclei is carried out by DNA-dependent RNA
      polymerases I, II, and III. Human RNA polymerase III (Pol III) transcribes small
      untranslated RNAs that include tRNAs, 5S RNA, U6 RNA, and some microRNAs.
      Increased Pol III transcription has been reported to accompany or cause cell
      transformation. Here we describe a Pol III subunit (RPC32beta) that led to the
      demonstration of two human Pol III isoforms (Pol IIIalpha and Pol IIIbeta).
      RPC32beta-containing Pol IIIbeta is ubiquitously expressed and essential for
      growth of human cells. RPC32alpha-containing Pol IIIalpha is dispensable for cell
      survival, with expression being restricted to undifferentiated ES cells and to
      tumor cells. In this regard, and most importantly, suppression of RPC32alpha
      expression impedes anchorage-independent growth of HeLa cells, whereas ectopic
      expression of RPC32alpha in IMR90 fibroblasts enhances cell transformation and
      dramatically changes the expression of several tumor-related mRNAs and that of a
      subset of Pol III RNAs. These results identify a human Pol III isoform and
      isoform-specific functions in the regulation of cell growth and transformation.

PMID- 20154272
TI  - When to go FISHing.

PMID- 20154273
TI  - Canadian Association of Pathologists-Association canadienne des pathologistes
      National Standards Committee/Immunohistochemistry: best practice recommendations
      for standardization of immunohistochemistry tests.
AB  - Immunohistochemical and immunocytochemical assays are highly complex diagnostic
      analyses used to aid in the accurate identification and biologic characterization
      of tissue types in neoplastic and nonneoplastic diseases. Immunohistochemical
      tests are applied mainly to the diagnosis of neoplasms. Some immunohistochemical
      tests provide information of important prognostic and predictive value in
      selected human neoplasms and, as such, are often critical for the appropriate and
      effective treatment of patients. This document provides recommendations and
      opinions of the Canadian Association of Pathologists-Association canadienne des
      pathologistes National Standards Committee/Immunohistochemistry relevant to
      clinical immunohistochemical terminology, classification of immunohistochemical
      tests based on risk assessment, and quality control and quality assurance and
      summarizes matters to be considered for appropriate
      immunohistochemical/immunocytochemical test development, performance, and
      interpretation in diagnostic pathology and laboratory medicine.

PMID- 20154274
TI  - Evidence levels for publications in pathology and laboratory medicine.

PMID- 20154271
TI  - Disruption of angiogenesis and tumor growth with an orally active drug that
      stabilizes the inactive state of PDGFRbeta/B-RAF.
AB  - Kinases are known to regulate fundamental processes in cancer including tumor
      proliferation, metastasis, neovascularization, and chemoresistance. Accordingly,
      kinase inhibitors have been a major focus of drug development, and several kinase
      inhibitors are now approved for various cancer indications. Typically, kinase
      inhibitors are selected via high-throughput screening using catalytic kinase
      domains at low ATP concentration, and this process often yields ATP mimetics that
      lack specificity and/or function poorly in cells where ATP levels are high.
      Molecules targeting the allosteric site in the inactive kinase conformation (type
      II inhibitors) provide an alternative for developing selective inhibitors that
      are physiologically active. By applying a rational design approach using a
      constrained amino-triazole scaffold predicted to stabilize kinases in the
      inactive state, we generated a series of selective type II inhibitors of
      PDGFRbeta and B-RAF, important targets for pericyte recruitment and endothelial
      cell survival, respectively. These molecules were designed in silico and screened
      for antivascular activity in both cell-based models and a Tg(fli1-EGFP) zebrafish
      embryogenesis model. Dual inhibition of PDGFRbeta and B-RAF cellular signaling
      demonstrated synergistic antiangiogenic activity in both zebrafish and murine
      models of angiogenesis, and a combination of previously characterized PDGFRbeta
      and RAF inhibitors validated the synergy. Our lead compound was selected as an
      orally active molecule with favorable pharmacokinetic properties which
      demonstrated target inhibition in vivo leading to suppression of murine
      orthotopic tumors in both the kidney and pancreas.

PMID- 20154275
TI  - Immunohistochemical evaluation of p16INK4A, E-cadherin, and cyclin D1 expression
      in melanoma and Spitz tumors.
AB  - We evaluated the usefulness of immunohistochemical examination for E-cadherin,
      p16, and cyclin D1 in discriminating melanoma from Spitz tumors. Immunoperoxidase
      staining was performed on formalin-fixed tissue specimens from 46 Spitz tumors
      and 42 concurrent melanoma specimens. The percentages of immunoreactive
      melanocytes in the epidermis and dermis were estimated semiquantitatively.
      Qualitatively abnormal immunoreactivity patterns were also tabulated. Dermal p16
      immunoreactivity was the best quantitative discriminator: decreased nuclear
      immunoreactivity (<25% of dermal melanocytes) was 3-fold more likely in melanoma
      than in Spitz tumors (P = .004). Loss of both nuclear and cytoplasmic dermal p16
      immunoreactivity was 8-fold more likely in melanoma (P = .01). Qualitative
      irregularities in the zonal distribution of E-cadherin immunoreactivity were 2
      fold higher in melanoma (P = .01), but these were often focal or subtle. There
      was no statistically significant difference in cyclin D1 immunoreactivity. In
      atypical Spitz tumors, the dermal p16 immunoreactivity and frequency of
      qualitative E-cadherin abnormalities were intermediate between those of ordinary
      Spitz nevi and melanoma. Also, contrasting immunoreactivity patterns were helpful
      in determining Breslow thickness in specimens containing melanoma and contiguous
      dermal nevi.

PMID- 20154276
TI  - Pathologic findings in novel influenza A (H1N1) virus ("Swine Flu") infection:
      contrasting clinical manifestations and lung pathology in two fatal cases.
AB  - Although novel influenza A (H1N1) virus infection has assumed pandemic
      proportions, there are few reports of the pathologic findings. Herein we describe
      the pathologic findings of novel influenza A (H1N1) infection based on findings
      in 2 autopsy cases. The first patient, a 36-year-old man, had flu-like symptoms;
      oseltamivir (Tamiflu) therapy was started 8 days after onset of symptoms, and he
      died on day 15 of his illness. At autopsy, the main finding was diffuse alveolar
      damage with extensive fresh intra-alveolar hemorrhage. The second patient, a 46
      year-old woman with alcoholism, was found unresponsive in a basement and brought
      to the hospital intoxicated and confused. Her condition deteriorated rapidly, and
      she died 4 days after admission. The main autopsy finding was acute
      bronchopneumonia with gram-positive cocci, intermixed with diffuse alveolar
      damage. The pathologic findings in these contrasting cases of novel influenza A
      (H1N1) infection are similar to those previously described for seasonal
      influenza. The main pathologic abnormality in fatal cases is diffuse alveolar
      damage, but it may be overshadowed by an acute bacterial bronchopneumonia.

PMID- 20154277
TI  - Shape is not associated with the origin of pericolonic tumor deposits.
AB  - Pericolonic tumor deposits (PTDs) are associated with an adverse outcome in
      colorectal cancer. According to the International Union Against Cancer they are
      classified as N1 or V1/V2 depending on their shape. This recommendation, however,
      is not well supported by the literature. To elucidate the origin of PTDs, we
      performed a histomorphologic study of 69 PTDs, which were found in 7 of 21
      colorectal specimens using the whole-mount step-section technique. Depending on
      the origin, the nodules were classified as venous invasions, lymphatic invasions,
      nerve sheath infiltrations, free PTDs, and continuous growth in 18 (26%), 3 (4%),
      6 (9%), 34 (49%), and 8 (12%) of 69 PTDs, respectively. Polycyclic and oval-round
      shapes were identified in all categories. Continuous growth was found only within
      the inner third of the adhering fat, whereas the other morphologic features were
      found in all regions. The data of this study do not support PTD classification on
      the basis of their shape.

PMID- 20154278
TI  - Conjunctive p16INK4a testing significantly increases accuracy in diagnosing high
      grade cervical intraepithelial neoplasia.
AB  - The histopathologic interpretation of cervical intraepithelial neoplasia (CIN) is
      subject to a high level of interobserver variability and a substantial number of
      false-positive and false-negative results. We assessed the impact of the
      conjunctive interpretation of p16(INK4a)-immunostained slides on the accuracy of
      community-based pathologists in diagnosing high-grade cervical intraepithelial
      neoplasia (CIN; CIN 2 and CIN 3) in biopsy specimens. Twelve pathologists
      rendered independent diagnoses on a set of 500 H&E-stained cervical punch and
      conization specimens. Results were compared with a dichotomized "gold standard"
      established by consensus of 3 gynecopathology experts. When p16(INK4a)
      immunostained slides were added and conjunctively interpreted with the H&E
      stained slides, a significant increase in diagnostic accuracy for the detection
      of high-grade CIN was observed (P = .0004). Sensitivity for high-grade CIN was
      increased by 13%, cutting the rate of false-negative results in half. Agreement
      of community-based pathologists in diagnosing high-grade CIN was significantly
      improved (mean kappa values advanced from 0.566 to 0.749; P < .0001).
      Reproducibility of p16(INK4a) stain interpretation was excellent (kappa = 0.899).
      Our results show that conjunctive interpretation of p16(INK4a)-stained slides
      could significantly improve the routine interpretation of cervical
      histopathology.

PMID- 20154279
TI  - PAX5 expression in nonhematopoietic tissues. Reappraisal of previous studies.
AB  - The Pax gene family encodes transcription factors with similar structures but
      distinctive roles in development and with limited expression in adult tissues.
      Reexpression of PAX proteins is frequently observed in human cancers, reflecting
      recapitulation of embryologic or developmental function. Defining expression of
      PAX family members is important in the immunohistochemical differential diagnosis
      of cancer, understanding oncogenesis, and defining targets for therapy.
      Immunostaining for PAX5 has become a commonly used technique in differential
      diagnosis of B-lineage hematologic malignancies. In seeking to define the range
      and degree of expression of PAX5 in nonhematologic pediatric cancers by
      immunohistochemical analysis with the anti-PAX5 monoclonal antibody routinely
      used in research and diagnosis, we observed strong immunostaining in a number of
      malignant tissues, including Wilms tumor. The pattern of expression of PAX5 in
      Wilms tumor was found to be identical to that of PAX2, raising the possibility of
      antibody cross-reactivity. This was subsequently confirmed by Western blotting
      and immunostaining of transfected cells and quantitative reverse transcriptase
      polymerase chain reaction. Since the same PAX5 monoclonal antibody has been used
      consistently in the literature, these findings indicate a need for reappraisal of
      published PAX5 immunostaining results.

PMID- 20154280
TI  - Hormone receptor and c-ERBB2 status in distant metastatic and locally recurrent
      breast cancer. Pathologic correlations and clinical significance.
AB  - Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are
      therapeutically and prognostically important markers in the management of breast
      carcinoma. They are not always analyzed in distant metastatic and locally
      recurrent breast cancers. We compared immunohistochemical expression in a series
      of primary breast carcinomas with their distant metastases (n = 72) and local
      recurrences (n = 45) and analyzed the impact of any changes on survival.
      Discordance rates between primary and metastatic and between primary and locally
      recurrent lesions, respectively, were 18% (13/72) and 13% (6/45) for ER, 42%
      (30/72) and 33% (15/45) for PR, and 7% (5/72) and 2% (1/45) for c-ERBB2. There
      was statistically significant discordance between primary and metastatic PR
      status (P = .017; kappa = 0.201). Among locally recurrent tumors, 15 (33%) of 45
      revealed discordance for PR (P = .006; kappa = 0.366). We observed a trend for
      shorter survival among women with ER- metastatic and locally recurrent tumors
      regardless of the primary tumor ER status. Our findings suggest a benefit for
      routine evaluation of ER, PR, and c-ERBB2 status in distant metastatic and
      locally recurrent breast cancer for therapeutic and prognostic purposes.

PMID- 20154281
TI  - The usefulness of IgG and IgM immunostaining of periportal inflammatory cells
      (plasma cells and lymphocytes) for the distinction of autoimmune hepatitis and
      primary biliary cirrhosis and their staining pattern in autoimmune hepatitis
      primary biliary cirrhosis overlap syndrome.
AB  - Autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome (OS)
      is a vaguely defined entity demonstrating features of AIH and PBC. We
      investigated the usefulness of IgG and IgM immunostaining for the distinction of
      AIH and PBC and their staining pattern in cases of possible OS. The approximate
      quantity of IgG+ and IgM+ periportal inflammatory cells in immunohistochemical
      analysis were compared in cases of AIH, PBC, and OS. AIH cases showed predominant
      IgG immunostaining of periportal inflammatory cells. A significant number of PBC
      cases also demonstrated IgG predominance rather than IgM. Six OS cases had IgG
      predominance, 4 had IgM predominance, and 1 was equivocal. The usefulness of IgG
      and IgM immunostaining is limited in PBC cases with IgM predominance for
      excluding AIH. IgG predominance is not specific for AIH. OS does not demonstrate
      either IgG or IgM predominance (P > .2) and does not help classify OS into either
      category.

PMID- 20154282
TI  - Responding to large-scale testing errors.
AB  - Extensive use of automation in the clinical laboratory creates the potential for
      systematic errors that affect a large number of patient results before the error
      is discovered. When a large-scale testing error is found, the approaches
      recommended for responding to individual medical mishaps are often inadequate.
      This report uses 2 case studies to illustrate some of the unique challenges
      facing laboratory managers confronted with a large-scale testing error. We
      identify 9 distinct constituencies that may be impacted by large-scale testing
      errors, each of which requires laboratory management's thoughtful and timely
      attention.

PMID- 20154283
TI  - Postmortem redistribution of fentanyl in blood.
AB  - Fentanyl concentrations were measured in postmortem specimens collected in 20
      medical examiner cases from femoral blood (FB), heart blood (HB), heart tissue,
      liver tissue, and skeletal muscle. Unique was a subset of 7 cases in which FB was
      obtained at 2 postmortem intervals, shortly after death (FB1) and at autopsy
      (FB2). The mean collection times of FB1 and FB2 after death were 4.0 and 21.6
      hours, respectively. Fentanyl concentrations for FB1 and FB2 ranged from
      undetectable to 14.6 microg/L (mean, 4.6 microg/L) and 2.0 to 52.5 microg/L
      (mean, 17.3 microg/L), respectively. Corresponding mean HB, liver tissue, and
      heart tissue fentanyl concentrations were 29.8 microg/L, 109.7 mg/kg, and 103.4
      mg/kg, respectively. The fentanyl HB/FB1 ratio (mean, 8.39) was higher compared
      with the corresponding HB/FB2 ratio (mean, 3.48). These results suggest that
      postmortem redistribution of fentanyl can occur in FB.

PMID- 20154284
TI  - A rapid and simple high-performance liquid chromatography assay for the
      leflunomide metabolite, teriflunomide (A77 1726), in renal transplant recipients.
AB  - Leflunomide (Arava), a drug with immunosuppressive and antiviral effects, is
      being used in renal transplant recipients, primarily for its action against BK
      polyomavirus (BKV), which affects 1% to 10% of renal transplant recipients and
      often causes failure of grafted kidneys. Leflunomide effects are solely due to an
      active metabolite, teriflunomide (formerly A77 1726). Trough blood concentrations
      of teriflunomide exceeding 40 microg/mL (148 micromol/L) are associated with
      progressive clearance of BKV. Toxic effects become increasingly apparent at
      higher concentrations. We have developed a rapid, simple, and robust high
      performance liquid chromatography (HPLC) method for therapeutic monitoring of
      teriflunomide in renal transplant recipients. Sample preparation is rapid, and
      each HPLC separation takes about 7 minutes. Intraday and interday coefficients of
      variation were 1.5% or less and 5.6% or less, respectively. The method was linear
      to 200 microg/mL (740 micromol/L), which is well above teriflunomide
      concentrations that are likely to be observed.

PMID- 20154285
TI  - Platelet count and prothrombin time help distinguish thrombotic thrombocytopenic
      purpura-hemolytic uremic syndrome from disseminated intravascular coagulation in
      adults.
AB  - Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) and
      disseminated intravascular coagulation (DIC) may have identical manifestations in
      adults. Because TTP-HUS is 90% fatal without plasma exchange, prompt diagnosis is
      essential. To test the hypothesis that routine laboratory assays can discriminate
      between the 2 entities, we retrospectively identified adult patients with TTP-HUS
      and matched each with 2 patients with DIC. Although the platelet count,
      prothrombin time (PT), and partial thromboplastin time were different (P < .05)
      between the 2 patient groups, after regression analysis, only PT and profound
      thrombocytopenia remained associated with TTP-HUS (P = .001 and P = .003,
      respectively). A platelet count of less than 20 x 10(3)/microL (20 x 10(9)/L) and
      a PT within 5 seconds of the upper limit of the reference interval had a
      specificity of 92% for TTP-HUS. Our data confirm that readily available
      laboratory assays in the proper clinical scenario can increase the likelihood of
      TTP-HUS over DIC.

PMID- 20154286
TI  - Clinicopathologic features of agranulocytosis in the setting of levamisole
      tainted cocaine.
AB  - Levamisole is a known contaminant of cocaine and, via this route, has been
      associated with otherwise unexplained agranulocytosis. Levamisole is currently
      present in the majority of cocaine samples seized by the US Drug Enforcement
      Agency. We identified 20 cases of unexplained agranulocytosis in our practice
      locations of Albuquerque, NM, and Vancouver, Canada. Epidemiologic investigation
      revealed recent or ongoing cocaine use in 14 cases (70%). Certain morphologic
      features, including circulating plasmacytoid lymphocytes, increased bone marrow
      plasma cells, and mild megakaryocytic hyperplasia, were associated with the
      cocaine-exposed group. Of 5 patients tested, 3 (60%) were HLA-B27+ and showed
      antineutrophil antibodies, consistent with known associations of levamisole
      induced agranulocytosis. One patient, who was positive for cocaine and levamisole
      by toxicology testing, died of infectious complications. Inadvertent consumption
      of levamisole via cocaine is a severely under-appreciated risk factor for
      agranulocytosis, and specific laboratory features are suggestive of this
      etiology.

PMID- 20154287
TI  - C-C chemokine receptor 1 expression in human hematolymphoid neoplasia.
AB  - Chemokine receptor 1 (CCR1) is a G protein-coupled receptor that binds to members
      of the C-C chemokine family. Recently, CCL3 (MIP-1alpha), a high-affinity CCR1
      ligand, was identified as part of a model that independently predicts survival in
      patients with diffuse large B-cell lymphoma (DLBCL). However, the role of
      chemokine signaling in the pathogenesis of human lymphomas is unclear. In normal
      human hematopoietic tissues, we found CCR1 expression in intraepithelial B cells
      of human tonsil and granulocytic/monocytic cells in the bone marrow.
      Immunohistochemical analysis of 944 cases of hematolymphoid neoplasia identified
      CCR1 expression in a subset of B- and T-cell lymphomas, plasma cell myeloma,
      acute myeloid leukemia, and classical Hodgkin lymphoma. CCR1 expression
      correlated with the non-germinal center subtype of DLBCL but did not predict
      overall survival in follicular lymphoma. These data suggest that CCR1 may be
      useful for lymphoma classification and support a role for chemokine signaling in
      the pathogenesis of hematolymphoid neoplasia.

PMID- 20154288
TI  - Acute promyelocytic leukemia at time of relapse commonly demonstrates cytogenetic
      evidence of clonal evolution and variability in blast immunophenotypic features.
AB  - Despite the success of the current therapy for patients with acute promyelocytic
      leukemia (APL), relapse occurs in up to 30% of patients. The characteristics of
      relapsed APL are not well described. We evaluated a group of APL cases at relapse
      and compared the clinicopathologic, immunophenotypic, molecular, and cytogenetic
      findings with those at initial diagnosis. From a group of 207 patients with APL,
      in 38 patients morphologic evidence of relapse developed. In 30 patients relapse
      was isolated to bone marrow, and 8 had extramedullary disease. Blasts were
      morphologically stable in 37 patients. Changes in the immunophenotypic profile
      were common, the most frequent being gain of CD34, HLA-DR, or CD33 and
      attenuation or loss of CD13. Cytogenetic changes were common at relapse. The size
      of the PML-RARalpha fusion transcript was invariable. We conclude that changes in
      the immunophenotype and cytogenetic evidence of clonal evolution are common in
      APL at the time of relapse.

PMID- 20154289
TI  - Molecular diversity of hemoglobin H disease in India.
AB  - This study was undertaken to evaluate the variable clinical expression of
      hemoglobin (Hb) H disease in India. For the study, alpha genotyping was done in 8
      patients with Hb H disease using multiplex polymerase chain reaction and DNA
      sequencing. The study revealed that 4 genotypes (- -(SEA)/ -alpha(3.7), - -(SA)/
      alpha(3.7), - -(SEA)/-alpha(3.7 Sallanches), - -alpha(3.7)/-alpha(3.7
      Sallanches)) were responsible for Hb H disease, the alpha+ thalassemia mutation (
      alpha(3.7) deletion) being the most common defect. The nondeletional mutation Hb
      Sallanches (alpha 2 codon 104 G --> A) was seen in 3 cases. Two unique and novel
      genotypes leading to Hb H disease were characterized (- -(SEA)/-alpha(3.7
      Sallanches) and -alpha(3.7)/-alpha(3.7 Sallanches)). Because a majority of
      patients with Hb H disease do not have severe manifestations, prenatal diagnosis
      is usually unwarranted in India.

PMID- 20154291
TI  - CAM5.2 is not identical to cytokeratins 8 and 18.

PMID- 20154292
TI  - Binding of an acceptor substrate analog enhances the enzymatic activity of human
      blood group B galactosyltransferase.
AB  - The hydrolysis of the donor substrate uridine diphosphate galactose (UDP-Gal) by
      human blood group B galactosyltransferase (GTB) has been followed by nuclear
      magnetic resonance in the presence and in the absence of an acceptor substrate
      analog. It is observed that the presence of the acceptor substrate analog
      promotes hydrolysis of UDP-Gal. Subsequent analysis of the kinetics of the
      enzymatic hydrolysis suggests that this effect is due to an increased affinity of
      GTB for UDP-Gal in the presence of the acceptor analog. Isothermal titration
      calorimetry experiments substantiate this conclusion. As hydrolysis may be
      understood as a glycosyl transfer reaction where water serves as universal
      acceptor, we suggest that in general the binding of acceptor substrates to
      retaining glycosyltransferases modulates the rate of glycosyl transfer. In fact,
      this may point to a general mechanism used by retaining glycosyltransferases to
      discriminate acceptor substrates under physiological conditions.

PMID- 20154293
TI  - Practical, individualized dosing: 21st century therapeutics and the clinical
      pharmacometrician.

PMID- 20154294
TI  - Quantifying pain relief following administration of a novel formulation of
      paracetamol (acetaminophen).
AB  - This article describes how a model-based analysis was used to aid development of
      a novel formulation technology. Paracetamol (acetaminophen) was used as the
      motivating example with 4 different formulations (2 developmental and 2
      commercial) compared using stochastic (Monte Carlo) pharmacokinetic (PK)
      pharmacodynamic (PD) simulations to explore potential differences in
      pharmacodynamic outcomes. PK models were developed from data collected during an
      intensively sampled, 4-arm crossover trial in 25 fasted healthy subjects,
      administered 1 g of paracetamol in 4 different formulations. The PK models were
      linked to a previously published PD model that quantified pain relief over time
      following tonsillectomy. The number needed to treat (NNT) was the primary numeric
      used to compare effectiveness. The developmental formulations were likely to
      produce faster and greater analgesia with an NNT (compared with placebo) to
      reduce pain by 50% over a 45-minute interval post dose of 2.75 and 2.88 compared
      with 4.31 and 3.2 for the commercial products. Over the course of 1 hour, all
      formulations were comparable. The stochastic simulations provided support that
      the novel formulation technology was likely to provide a clinically meaningful
      advantage and should be developed further.

PMID- 20154295
TI  - Agency and communication challenges in discussions of informed consent in
      pediatric cancer research.
AB  - In this article we examine the discourse of four focus groups we conducted at a
      pediatric research hospital in which we queried teenage patients, parents,
      nurses, and physicians about their perceptions of the informed consent process in
      research. Autonomy, as the goal of informed consent, is a murky concept, with
      some ethicists questioning the possibility that it can ever be attained. We argue
      that it might be more productive to consider agency, which we define as language
      and action that are constructed, negotiated, and maintained through effective
      communication. Our goal was to understand how individuals rhetorically
      constructed agency in discussions of informed consent experiences. After
      transcribing and coding the focus group interviews, we identified six aspects of
      agency in participants' discourse: (a) defining roles, (b) seeking information,
      (c) providing information, (d) supporting others, (e) making decisions, and (f)
      claiming agency for self. Examining these aspects of agency indicated that
      efforts to improve the informed consent process must address: (a) status
      differentials, (b) role definitions, (c) information flow, and (d) relationships.

PMID- 20154296
TI  - Tell me--show me: using combined focus group and photovoice methods to gain
      understanding of health issues in rural Guatemala.
AB  - As health researchers, our training is more literary than visual. We are only
      beginning to learn about the value of photography as a qualitative data
      collection method. In this article we describe a project utilizing focus groups
      and photovoice, sequentially, to gather information about health-related
      conditions in rural Guatemala. In the first phase, the perceptions of a group of
      comadronas (birth attendants) were elicited using traditional focus group
      methodology. In the second phase, conducted several months later, the photovoice
      method was utilized. During this phase, the same participants viewed and
      responded to photographs taken during the intervening period by some of the phase
      one participants. The findings from this two-phase approach support those from
      other studies that suggest that photovoice provides more in-depth data and the
      potential for bringing out additional information that might not emerge during
      traditional interviews or focus group discussions.

PMID- 20154297
TI  - Analyzing interactional contexts in a data-sharing focus group.
AB  - In this article we describe the use of a data-sharing focus group for
      triangulation with face-to-face interviews. In contrast to member-checking
      triangulation, this focus group was undertaken to provide a different
      interactional context to analyze moral discourses in talk about asthma medicine
      taking. Using principles of discursive psychology to analyze data, participants
      adopted strategies to manage dilemmas of identification with research findings.
      Talk about medicine taking was contextualized to the demands of the interaction.
      Strategies included avoiding direct reference to findings; collectively aligning
      with medical perspectives; and using stories to carry opinions. Participants also
      expressed moral discourses around managing asthma in everyday life. These
      discursive variations strengthened assertions of the role of morality in
      participants' talk and highlighted advantages in engaging with participants'
      strategies in focus groups. Different viewpoints identified in this research
      create problems for member checking, suggesting that researchers need to be
      sensitive in considering methods of sharing data with participants.

PMID- 20154298
TI  - Superwoman schema: African American women's views on stress, strength, and
      health.
AB  - Researchers have suggested that health disparities in African American women,
      including adverse birth outcomes, lupus, obesity, and untreated depression, can
      be explained by stress and coping. The Strong Black Woman/Superwoman role has
      been highlighted as a phenomenon influencing African American women's experiences
      and reports of stress. The purpose of this study was to develop a preliminary
      conceptual framework for Superwoman Schema (SWS) by exploring women's
      descriptions of the Superwoman role; perceptions of contextual factors, benefits,
      and liabilities; and beliefs regarding how it influences health. Analysis of
      eight focus group discussions with demographically diverse African American women
      yielded themes characterizing the Superwoman role and personal or sociohistorical
      contextual factors. Participants reported that the Superwoman role had benefits
      (preservation of self and family or community) and liabilities (relationship
      strain, stress-related health behaviors, and stress embodiment). The SWS
      framework might be used to enhance future research on stress and African American
      women's health.

PMID- 20154299
TI  - Using focus groups in community-based participatory research: challenges and
      resolutions.
AB  - A community-based participatory approach requires that community members be
      involved in all phases of the research process. We describe three focus group
      studies with American Indians in Kansas and Missouri, using a newly developed
      method of conducting and analyzing focus groups with community input (72 focus
      groups, 519 participants). We conducted two needs assessment studies focused on
      barriers to breast and colorectal cancer screening and one study focused on
      Internet use for gathering health information. Community members and researchers
      collaborated to develop guides for the focus group moderators. Community
      organizations and our community advisory board conducted recruitment, and we
      trained and employed community members as moderators, assistant moderators, and
      analysts. Our community partners also helped with dissemination of research
      findings to their constituents. The methodologic approach and data from these
      three studies will allow us to more appropriately address health disparities in
      the American Indian community, with full community support for our research.

PMID- 20154300
TI  - Culturally sensitive care 1969-2000: the Indian Chicano Health Center.
AB  - The provision of culturally competent health care is a priority for providers
      across the United States. However, for biomedicine, what does the provision of
      culturally sensitive, culturally competent care actually mean? To address this
      question, I use a case study of 30 years of practice at an urban free clinic
      founded to provide culturally sensitive health care. The model of culturally
      sensitive health care presented is compared to the U.S. Department of Health and
      Human Services standards for providing culturally and linguistically appropriate
      care (CLAS). I conclude that, for the most part, the urban free clinic founders
      and community participants through its history generated similar responses to
      CLAS in their effort to effectively serve Latino/Latina and Native American
      populations. However, the order in which the urban free clinic implemented
      cultural sensitivity measures seems to follow the theoretical concept of cultural
      lag, where material/nonmaterial culture transference differs in situations of
      culture contact and social change.

PMID- 20154301
TI  - Conceptualizing community: the experience of mental health consumers.
AB  - In this article we describe a focus group study of the perspectives of diverse
      groups of mental health consumers on the concept of community. We identify the
      core domains that constitute the notion of community, and commonalities and
      differences in the perception of community along the lines of ethnicity and
      sexual orientation/gender identity. Seven focus groups were conducted with a
      total of 62 participants. Transcripts were analyzed using the grounded theory
      approach.Two domains-togetherness and community acceptance-emerged as common to
      four types of communities that were most frequently mentioned in the focus group
      discussion. Our findings show that identities other than those associated with
      mental illness and the role of service user are critical to the understanding of
      the psychological sense of community among persons with psychiatric disabilities.
      We suggest that mental health providers empower consumers to expand their
      "personal communities" beyond that of mental health clients using their diverse
      identities, and design interventions for addressing the stigma emanating from
      identities that are discriminated against by the wider society.

PMID- 20154302
TI  - The GHESKIO refugee camp after the earthquake in Haiti--dispatch 2 from Port-au
      Prince.

PMID- 20154303
TI  - Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell
      carcinoma (RCC): a report from the Juvenile RCC Network.
AB  - BACKGROUND: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype
      affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted
      therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents
      and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients.
      PATIENTS AND METHODS: Patients with Xp11 translocation/TFE3 fusion gene
      metastatic RCC who had received targeted therapy were identified. Nuclear TFE3
      positivity was confirmed by reviewing pathology slides. Responses according to
      RECIST criteria, progression-free survival (PFS), and overall survival (OS) were
      analyzed. RESULTS: Overall, 53 patients were identified; 23 had metastatic
      disease, and of these 21 had received targeted therapy (median age 34 years).
      Seven patients achieved an objective response. In first line, median PFS was 8.2
      months [95% confidence interval (CI) 2.6-14.7 months] for sunitinib (n = 11)
      versus 2 months (95% CI 0.8-3.3 months) for cytokines (n = 9) (log-rank P =
      0.003). Results for further treatment (second, third, or fourth line) were as
      follows: all three patients receiving sunitinib had a partial response (median
      PFS 11 months). Seven of eight patients receiving sorafenib had stable disease
      (median PFS 6 months). One patient receiving mTOR inhibitors had a partial
      response and six patients had stable disease. Median OS was 27 months with a 19
      months median follow-up. CONCLUSION: In Xp11 translocation RCC, targeted therapy
      achieved objective responses and prolonged PFS similar to those reported for
      clear-cell RCC.

PMID- 20154304
TI  - Predictive values of hCG clearance for risk of methotrexate resistance in low
      risk gestational trophoblastic neoplasias.
AB  - BACKGROUND: Early identification of patients at high risk for chemoresistance
      among those treated with methotrexate (MTX) for low-risk gestational
      trophoblastic neoplasia (GTN) is needed. We modeled human chorionic gonadotropin
      (hCG) decline during MTX therapy using a kinetic population approach to calculate
      individual hCG clearance (CL(hCG)) and assessed the predictive value of CL(hCG)
      for MTX resistance. PATIENTS AND METHODS: A total of 154 patients with low-risk
      GTN treated with 8-day MTX regimen were retrospectively studied. NONMEM was used
      to model hCG decrease equations between day 0 and day 40 of chemotherapy.
      Receiver operating characteristic curve analysis defined the best CL(hCG)
      threshold. Univariate/multivariate survival analyses determined the predictive
      value of CL(hCG) and compared it with published predictive factors. RESULTS: A
      monoexponential equation best modeled hCG decrease: hCG(t) = 3900 x e(-0.149 x
      t). Median CL(hCG) was 0.57 l/day (quartiles: 0.37-0.74). Only choriocarcinoma
      pathology [yes versus no: hazard ratio (HR) = 6.01; 95% confidence interval (CI)
      2.2-16.6; P < 0.001] and unfavorable CL(hCG) quartile (< or =0.37 versus >0.37
      l/day: HR = 6.75; 95% CI 2.7-16.8; P < 0.001) were significant independent
      predictive factors of MTX resistance risk. CONCLUSION: In the second largest
      cohort of low-risk GTN patients reported to date, choriocarcinoma pathology and
      CL(hCG) < or =0.37 l/day were major independent predictive factors for MTX
      resistance risk.

PMID- 20154305
TI  - A doubly robust test for gene-environment interaction in family-based studies of
      affected offspring.
AB  - We develop a locally efficient test for (multiplicative) gene-environment
      interaction in family studies that collect genotypic information and
      environmental exposures for affected offspring along with genotypic information
      for their parents or relatives. The proposed test does not require modeling the
      effects of environmental exposures and is doubly robust in the sense of being
      valid if either a model for the main genetic effect holds or a model for the
      expected environmental exposure (given the offspring affection status and
      parental mating types) but not necessarily both. It extends the FBAT-I to allow
      for missing parental mating types and families of arbitrary size. Simulation
      studies and the analysis of an Alzheimer's disease study confirm the adequate
      performance of the proposed test.

PMID- 20154306
TI  - An examination of special focus facility nursing homes.
AB  - PURPOSE: Nursing facilities that are determined to have a greater number of
      quality problems, more serious problems than average, and a demonstrated pattern
      of quality problems are included in the Special Focus Facility (SFF) initiative.
      The purpose of this research was to provide descriptive information on these SFFs
      and to examine the quality characteristics of these facilities. DESIGN AND
      METHODS: The 1997 through 2008 On-line Survey, Certification And Reporting data
      and 2003 through 2008 Nursing Home Compare data were used. Descriptive analyses,
      including t tests, were used to compare the 2 groups of facilities (i.e., SFF
      nursing facilities and non-SFF nursing facilities). RESULTS: Staffing for
      registered nurses and nurse aides was lower in SFFs; all citations, quality of
      care citations, and J, K, and L citations were more frequent in SFFs; and quality
      indicators such as pressure ulcers and use of antipsychotic drugs were more
      prevalent in SFFs. IMPLICATIONS: SFF targeting would appear to be accurate with
      respect to nursing facilities having multiple poor quality issues and chronic
      poor quality.

PMID- 20154307
TI  - The impact of special focus facility nursing homes on market quality.
AB  - PURPOSE: Special Focus Facilities (SFFs) are nursing facilities designated by the
      Centers for Medicare & Medicaid Services to be of chronic poor quality.
      Relatively few nursing facilities are included in this initiative. The purpose of
      this research was to examine whether nursing facilities included in the 2007 SFF
      initiative subsequently influenced the quality of other facilities in their
      market. DESIGN AND METHODS: The 2007 On-line Survey, Certification and Reporting
      data and 2007 through 2008 Nursing Home Compare data were used. Multivariate
      analyses examining the quality indicators at the county level were used to
      examine the market influence of SFFs. RESULTS: Of the 135 nursing facilities
      included in the 2007 SFF initiative, 58 (i.e., 42%) have shown significant
      improvement in quality. When examining all nursing facilities, of the 22
      multivariate models 6 showed that the quality indicators of non-SFFs were
      significantly different in counties with SFFs. When examining nursing facilities
      with the lowest quality, of the 22 multivariate models 10 showed that the quality
      indicators of non-SFFs were significantly different in counties with SFFs.
      IMPLICATIONS: The use of the SFF initiative may have influenced aggregate market
      level nursing facility quality.

PMID- 20154308
TI  - High incidence of Salmonella Dublin in cattle and sheep.

PMID- 20154309
TI  - Occurrence of Mycoplasma hyopneumoniae infections in suckling and nursery pigs in
      a region of high pig density.
AB  - The occurrence of Mycoplasma hyopneumoniae infections in young pigs was surveyed
      in a retrospective study of 1122 datasets obtained from routine diagnostics where
      either suckling or nursery pigs were examined for M hyopneumoniae in lung tissue.
      Findings were correlated with the presence of lung lesions, detection of other
      respiratory pathogens, vaccination history and parameters describing the herd of
      origin. The prevalence of M hyopneumoniae in lung tissue from 201 suckling pigs
      was 2.0 per cent and, therefore, significantly lower than in lung tissue from 921
      nursery pigs, which was 9.3 per cent. Previous use of antimicrobials and the
      vital status of the pigs when delivered for postmortem examination did not
      influence the detection of M hyopneumoniae infection. The presence of the porcine
      reproductive and respiratory syndrome virus (PRRSV)-EU genotype, Pasteurella
      multocida, Haemophilus parasuis, Mycoplasma hyorhinis or Streptococcus suis was
      correlated with a higher probability of also finding M hyopneumoniae. The history
      of vaccination, the time of the first or second application, and the type of
      vaccine (one- versus two-shot) did not influence the detection of M
      hyopneumoniae. A correlation between the type of herd and the presence of M
      hyopneumoniae was statistically insignificant and no effect of farrowing rhythm
      could be confirmed.

PMID- 20154310
TI  - Malignant histiocytosis and other causes of death in Bernese mountain dogs in
      Denmark.
AB  - To determine the causes of death in Bernese mountain dogs, to assess the
      prevalence of malignant histiocytosis in the Danish Bernese mountain dog
      population, and to assess whether a hereditary pattern for this disease exists,
      756 questionnaires were sent to members of the Danish Bernese Mountain Dog Club
      requesting information regarding the life span and causes of death of their dogs.
      A response rate of 57.7 per cent was achieved, giving information for 812 dogs,
      of which 290 had died. The average life span was 7.1 years. The most prevalent
      causes of death were neoplasia (42.1 per cent), old age (10.3 per cent), kidney
      disease (6.9 per cent), infection (5.9 per cent), skeletal problems (5.2 per
      cent), heart disease (3.8 per cent) and behavioural causes (3.5 per cent).
      Thirteen dogs were diagnosed with malignant histiocytosis, 11 of which were
      genealogically related.

PMID- 20154311
TI  - Surveillance for exotic ticks on companion animals in the UK.

PMID- 20154312
TI  - Ultrasonographic determination of body wall thickness at standing left laparotomy
      site in dairy cows.

PMID- 20154313
TI  - Pathological abnormalities of the reproductive tracts of ewes in Basra, Iraq.

PMID- 20154314
TI  - Use of local hyperthermia to treat sporotrichosis in a cat.

PMID- 20154316
TI  - A public or private profession?

PMID- 20154317
TI  - Vaccination against bovine TB with Mycobacterium microti.

PMID- 20154318
TI  - Official Veterinarian fee review.

PMID- 20154319
TI  - Official Veterinarian fee review.

PMID- 20154320
TI  - Official Veterinarian fee review.

PMID- 20154322
TI  - Apparent low toxicity of yew for roe deer (Capreolus capreolus).

PMID- 20154323
TI  - PMWS in pigs in Iceland.

PMID- 20154324
TI  - Fibril morphology and tendon mechanical properties in patellar tendinopathy:
      effects of heavy slow resistance training.
AB  - BACKGROUND: Patellar tendinopathy is characterized by pathologic abnormalities.
      Heavy slow resistance training (HSR) is effective in the management of patellar
      tendinopathy, but the underlying functional mechanisms remain elusive. PURPOSE:
      To investigate fibril morphology and mechanical properties in patellar
      tendinopathy and the effect of HSR on these properties. STUDY DESIGN: Cohort
      study; Level of evidence, 2. METHODS: Eight male patients with patellar
      tendinopathy completed 12 weeks of HSR. Nine healthy subjects served as controls.
      Assessments were conducted at baseline and at 12 weeks. Patients assessed
      symptoms/function and maximal tendon pain during activity. Tendon biopsy samples
      were analyzed for fibril density, volume fraction, and mean fibril area. Tendon
      mechanical properties were assessed using force and ultrasonography samplings.
      RESULTS: Patients improved in symptoms/function (P = .02) and maximal tendon pain
      during activity (P = .008). Stiffness and modulus of control and tendinopathy
      tendons were similar at baseline. Stiffness remained unaffected in control
      tendons (3487 +/- 392 to 3157 +/- 327 N/mm, P = .57) but declined in
      tendinopathic tendons at 12 weeks (3185 +/- 187 to 2701 +/- 201 N/mm, P = .04).
      At baseline, fibril volume fraction was equal, fibril density smaller (P = .03),
      and mean fibril area tended to be higher in tendinopathy versus controls (P =
      .07). Fibril morphology remained unchanged in controls but fibril density
      increased (70% +/- 18%, P = .02) and fibril mean area decreased (-26% +/- 21%, P
      = .04) in tendinopathic tendons after HSR. CONCLUSION: Fibril morphology is
      abnormal in tendinopathy, but tendon mechanical properties are not. Clinical
      improvements after HSR were associated with changes in fibril morphology toward
      normal fibril density and mean fibril area. Heavy slow resistance training
      improved the clinical outcome of patellar tendinopathy, and these improvements
      were associated with normalization of fibril morphology, most likely due to a
      production of new fibrils.

PMID- 20154325
TI  - MutLalpha and proliferating cell nuclear antigen share binding sites on MutSbeta.
AB  - MutSbeta (MSH2-MSH3) mediates repair of insertion-deletion heterologies but also
      triggers triplet repeat expansions that cause neurological diseases. Like other
      DNA metabolic activities, MutSbeta interacts with proliferating cell nuclear
      antigen (PCNA) via a conserved motif (QXX(L/I)XXFF). We demonstrate that MutSbeta
      PCNA complex formation occurs with an affinity of approximately 0.1 microM and a
      preferred stoichiometry of 1:1. However, up to 20% of complexes are multivalent
      under conditions where MutSbeta is in molar excess over PCNA. Conformational
      studies indicate that the two proteins associate in an end-to-end fashion in
      solution. Surprisingly, mutation of the PCNA-binding motif of MutSbeta not only
      abolishes PCNA binding, but unlike MutSalpha, also dramatically attenuates
      MutSbeta-MutLalpha interaction, MutLalpha endonuclease activation, and
      bidirectional mismatch repair. As predicted by these findings, PCNA competes with
      MutLalpha for binding to MutSbeta, an effect that is blocked by the cell cycle
      regulator p21(CIP1). We propose that MutSbeta-MutLalpha interaction is mediated
      in part by residues ((L/I)SRFF) embedded within the MSH3 PCNA-binding motif. To
      our knowledge this is the first case where residues important for PCNA binding
      also mediate interaction with a second protein. These findings also indicate that
      MutSbeta- and MutSalpha-initiated repair events differ in fundamental ways.

PMID- 20154326
TI  - Flavobacterium ponti sp. nov., isolated from seawater.
AB  - A Gram-stain-negative, non-flagellated, non-gliding, yellow-pigmented and rod
      shaped bacterial strain, designated GSW-R14(T), was isolated from seawater of
      Geoje Island in the South Sea, Korea. Strain GSW-R14(T) grew optimally at 25 
      degrees C, at pH 7.0-8.0 and in the presence of 2 % (w/v) NaCl. Phylogenetic
      analyses based on 16S rRNA gene sequences showed that strain GSW-R14(T) belonged
      to the genus Flavobacterium, joining Flavobacterium gelidilacus LMG 21477(T) by a
      bootstrap resampling value of 100 %. Strain GSW-R14(T) exhibited 97.6 % 16S rRNA
      gene sequence similarity to F. gelidilacus LMG 21477(T) and similarities of 91.2
      95.2 % to other members of the genus Flavobacterium. Strain GSW-R14(T) contained
      MK-6 as the predominant menaquinone. The fatty acid profile of strain GSW-R14(T)
      was similar to that of F. gelidilacus LMG 21477(T). The DNA G+C content of strain
      GSW-R14(T) was 31.4 mol% and its DNA-DNA relatedness with F. gelidilacus LMG
      21477(T) was 31 %. Strain GSW-R14(T) could be distinguished from F. gelidilacus
      and the other species of the genus Flavobacterium by its phylogenetic and genetic
      distinctiveness and by several phenotypic properties. On the basis of these data,
      strain GSW-R14(T) is considered to represent a novel species of the genus
      Flavobacterium, for which the name Flavobacterium ponti sp. nov. is proposed; the
      type strain is GSW-R14(T) (=KCTC 22802(T) =CCUG 58402(T)).

PMID- 20154327
TI  - Thermasporomyces composti gen. nov., sp. nov., a thermophilic actinomycete
      isolated from compost.
AB  - A thermophilic, Gram-positive bacterium that formed a branched vegetative
      mycelium was isolated from compost. The strain, designated I3(T), grew at
      temperatures between 35 and 62  degrees C, with optimum growth at 50-55  degrees
      C. No growth was observed below 29  degrees C or above 65  degrees C. The pH
      range for growth was 5.7-10.0, the pH for optimum growth was 7.0 and no growth
      was observed below pH 5.6 or above pH 10.8. The DNA G+C content of strain I3(T)
      was 69.2 mol%. The major fatty acids found were C(15 : 0) iso (14.2 %), C(15 : 0)
      anteiso (12.1 %), C(17 : 0) iso (16.3 %) and C(17 : 0) anteiso (21.7 %). The
      major menaquinones were MK-9(H(4)), MK-10(H(4)) and MK-11(H(4)). The cell wall
      contained glutamic acid, glycine, alanine and ll-diaminopimelic acid in a molar
      ratio of 1.0 : 3.9 : 0.6 : 0.5. The polar lipids consisted of ninhydrin-positive
      phosphoglycolipids, phosphatidylglycerol, diphosphatidylglycerol and an unknown
      glycolipid. The cell-wall sugars were rhamnose and arabinose. 16S rRNA gene
      sequence analysis assigned this actinomycete to the family Nocardioidaceae, but
      its 16S rRNA gene sequence shared no more than 95.5 % similarity with those of
      other members of the family. The chemotaxonomic and phenotypic characteristics of
      strain I3(T) differed in some respects from those of members of the genus
      Actinopolymorpha, the most closely related genus. Therefore, strain I3(T)
      represents a novel species in a new genus of the family Nocardioidaceae, for
      which the name Thermasporomyces composti gen. nov., sp. nov. is proposed. The
      type strain of the type species is I3(T) (=JCM 16421(T)=DSM 22891(T)).

PMID- 20154328
TI  - Phycicoccus cremeus sp. nov., isolated from forest soil, and emended description
      of the genus Phycicoccus.
AB  - A bacterial strain, designated V2M29(T), was isolated from forest soil collected
      in the Changbai Mountains, Heilongjiang Province, China. Cells of strain V2M29(T)
      were Gram-positive, rod-shaped (0.5-0.8 MUm in diameter and 1.5-2.0 MUm in
      length), strictly aerobic and non-motile. Colonies produced on R2A agar plates
      were creamy, smooth, circular and 0.3-0.8 mm in diameter. Strain V2M29(T) grew at
      14-35  degrees C (optimum, 29  degrees C), at pH 4.1-10.0 (optimum, pH 7.0-8.0)
      and in the presence of 0-7.0 % (w/v) NaCl (optimum, 0-2.0 %). Strain V2M29(T)
      contained MK-8(H(4)) as the major respiratory quinone and iso-C(15 : 0) (20.9 %),
      iso-C(16 : 0) (18.5 %), C(17 : 1)omega8c (16.7 %) and 10-methyl-C(17 : 0) (9.2 %)
      as the major cellular fatty acids. The cell-wall peptidoglycan type was based on
      meso-2,6-diaminopimelic acid and the acyl type of the muramic acid was acetyl.
      Diphosphatidylglycerol, phosphatidylinositol and six unknown glycolipids were the
      major polar lipids. The G+C content of the DNA was 72.0 mol% (T(m)). 16S rRNA
      gene sequence analysis indicated that strain V2M29(T) was phylogenetically
      related to members of the genus Phycicoccus, with sequence similarities ranging
      from 96.6-97.8 %. The DNA-DNA relatedness values of strain V2M29(T) to
      Phycicoccus dokdonensis DS-8(T) and Phycicoccus bigeumensis DSM 19264(T) were
      32.5+/-3.3 % and 29.2+/-2.3 %, respectively. Based on these results, it is
      concluded that strain V2M29(T) represents a novel species of the genus
      Phycicoccus, for which the name Phycicoccus cremeus sp. nov. is proposed, with
      V2M29(T) (=CGMCC 1.6963(T) =NBRC 104261(T)) as the type strain.

PMID- 20154329
TI  - Streptomyces hyderabadensis sp. nov., an actinomycete isolated from soil.
AB  - A novel actinomycete, designated strain OU-40(T), was isolated from farm soil
      collected from the Hyderabad region of Andhra Pradesh, southern India. The strain
      was found to have morphological and chemotaxonomic characteristics typical of
      species of the genus Streptomyces. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that strain OU-40(T) belonged to the genus Streptomyces, and
      was related most closely to Streptomyces pactum NBRC 13433(T) (99.0 % sequence
      similarity), Streptomyces olivaceus NBRC 12805(T) (99.0 %) and Streptomyces
      parvulus NBRC 13193(T) (98.8 %). Strain OU-40(T) could be distinguished from the
      type strains of its closest phylogenetic relatives based on levels of DNA-DNA
      relatedness and comparison of morphological and phenotypic data. It is therefore
      concluded that strain OU-40(T) represents a novel species of the genus
      Streptomyces, for which the name Streptomyces hyderabadensis sp. nov. is
      proposed. The type strain is OU-40(T) (=CCTCC AA 209024(T) =PCM 2692(T)).

PMID- 20154330
TI  - Gordonia humi sp. nov., isolated from soil.
AB  - A Gram-stain-positive, non-endospore-forming actinobacterium (CC-12301(T)) was
      isolated from soil attached to a spawn used in the laboratory to grow the edible
      mushroom Agaricus brasiliensis. Based on 16S rRNA gene sequence similarities,
      strain CC-12301(T) was shown to belong to the genus Gordonia and was most closely
      related to the type strains of Gordonia hydrophobica (97.6 % similarity),
      Gordonia terrae (97.5 %), Gordonia amarae (97.5 %) and Gordonia malaquae (97.4
      %). The quinone system was determined to consist predominantly of menaquinone MK
      9(H(2)), minor amounts of MK-8(H(2)) and MK-7(H(2)). The polar lipid profile
      consisted of the major compounds diphosphatidylglycerol and
      phosphatidylethanolamine, moderate amounts of two phosphatidylinositol mannosides
      and phosphatidylinositol and minor amounts of phosphatidylglycerol, three
      unidentified glycolipids, two phosphoglycolipids and a phospholipid. Mycolic
      acids were present. These chemotaxonomic traits and the major fatty acids, which
      were C(16 : 1) cis9, C(16 : 0), C(18 : 1) and tuberculostearic acid (10-methyl
      C(18 : 0)), supported the affiliation of strain CC-12301(T) to the genus
      Gordonia. The results of physiological and biochemical tests allowed clear
      phenotypic differentiation of strain CC-12301(T) from the most closely related
      Gordonia species. Strain CC-12301(T) therefore represents a novel species, for
      which the name Gordonia humi sp. nov. is proposed, with the type strain CC
      12301(T) (=DSM 45298(T) =CCM 7727(T)).

PMID- 20154331
TI  - Methanoregula boonei gen. nov., sp. nov., an acidiphilic methanogen isolated from
      an acidic peat bog.
AB  - A novel acidiphilic, hydrogenotrophic methanogen, designated strain 6A8(T), was
      isolated from an acidic (pH 4.0-4.5) and ombrotrophic (rain-fed) bog located near
      Ithaca, NY, USA. Cultures were dimorphic, containing thin rods (0.2-0.3 MUm in
      diameter and 0.8-3.0 MUm long) and irregular cocci (0.2-0.8 MUm in diameter). The
      culture utilized H(2)/CO(2) to produce methane but did not utilize formate,
      acetate, methanol, ethanol, 2-propanol, butanol or trimethylamine. Optimal growth
      conditions were near pH 5.1 and 35  degrees C. The culture grew in basal medium
      containing as little as 0.43 mM Na(+) and growth was inhibited completely by 50
      mM NaCl. To our knowledge, strain 6A8(T) is one of the most acidiphilic (lowest
      pH optimum) and salt-sensitive methanogens in pure culture. Acetate, coenzyme M,
      vitamins and yeast extract were required for growth. It is proposed that a new
      genus and species be established for this organism, Methanoregula boonei gen.
      nov., sp. nov. The type strain of Methanoregula boonei is 6A8(T) (=DSM 21154(T)
      =JCM 14090(T)).

PMID- 20154332
TI  - Marinobacterium coralli sp. nov., isolated from mucus of coral (Mussismilia
      hispida).
AB  - A Gram-negative, aerobic bacterium, designated R-40509(T), was isolated from
      mucus of the reef builder coral (Mussismilia hispida) located in the Sao
      Sebastiao Channel, Sao Paulo, Brazil. The strain was oxidase-positive and
      catalase-negative, and required Na(+) for growth. Its phylogenetic position was
      in the genus Marinobacterium and the closest related species were Marinobacterium
      sediminicola, Marinobacterium maritimum and Marinobacterium stanieri; the isolate
      exhibited 16S rRNA gene sequence similarities of 97.5-98.0 % with the type
      strains of these species. 16S rRNA gene sequence similarities with other type
      strains of the genus Marinobacterium were below 96 %. DNA-DNA hybridizations
      between strain R-40509(T) and the type strains of the phylogenetically closest
      species of the genus Marinobacterium revealed less than 70 % DNA-DNA relatedness,
      supporting the novel species status of the strain. Phenotypic characterization
      revealed that the strain was able to grow at 15-42  degrees C and in medium
      containing up to 9 % NaCl. The isolate could be differentiated from
      phenotypically related species by several features, including its ability to
      utilize d-alanine, l-alanine, bromosuccinic acid, beta-hydroxybutyric acid and
      alpha-ketovaleric acid, but not acetate or l-arabinose. It produced acetoin
      (Voges-Proskauer), but did not have esterase lipase (C8) or catalase activities.
      It possessed C(18 : 1)omega7c (35 %), summed feature 3 (iso-C(15 : 0) 2-OH and/or
      C(16 : 1)omega7c; 25 %) and C(16 : 0) (22 %) as major cellular fatty acids. The
      DNA G+C content was 58.5 mol%. The name Marinobacterium coralli sp. nov. is
      proposed to accommodate this novel isolate; the type strain is R-40509(T) (=LMG
      25435(T) =CAIM 1449(T)).

PMID- 20154333
TI  - Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural
      characterization and immunoreactivity in cerebrospinal fluid.
AB  - Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer).
      The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by
      electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear
      magnetic resonance (NMR) spectroscopy complementing previous NMR spectroscopy and
      gas chromatography-mass spectrometry to be 3-O-acetyl-sphingosine-GalCer
      derivatives with galactose O-acetyl modifications. FMC-5 and FMC-6 are 3-O-acetyl
      sphingosine-2,3,4,6-tetra-O-acetyl-GalCer with nonhydroxy and hydroxy-N-fatty
      acids, while FMC-7 has an additional O-acetylation of the 2-hydroxy-fatty acid.
      The immuno-reactivity in human cerebrospinal fluid (CSF) to these acetylated
      glycolipids was examined in central nervous system (CNS) infectious disease,
      noninflammatory disorders, and multiple sclerosis (MS). Screening for lipid
      binding in MS and other neurological disease groups revealed that the greatest
      anti-hydrophobic FMC reactivity was observed in the inflammatory CNS diseases
      (meningitis, meningo-encephalitis, and subacute sclerosing panencephalitis). Some
      MS patients had increased reactivity with the hydrophobic FMCs and with
      glycoglycerophospholipid MfGL-II from Mycoplasma fermentans. The cross-reactivity
      of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility
      that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease
      are linked.

PMID- 20154334
TI  - The rise and fall of rosiglitazone.

PMID- 20154335
TI  - Proteome analysis of the penicillin producer Penicillium chrysogenum:
      characterization of protein changes during the industrial strain improvement.
AB  - Proteomics is a powerful tool to understand the molecular mechanisms causing the
      production of high penicillin titers by industrial strains of the filamentous
      fungus Penicillium chrysogenum as the result of strain improvement programs.
      Penicillin biosynthesis is an excellent model system for many other bioactive
      microbial metabolites. The recent publication of the P. chrysogenum genome has
      established the basis to understand the molecular processes underlying penicillin
      overproduction. We report here the proteome reference map of P. chrysogenum
      Wisconsin 54-1255 (the genome project reference strain) together with an in-depth
      study of the changes produced in three different strains of this filamentous
      fungus during industrial strain improvement. Two-dimensional gel electrophoresis,
      peptide mass fingerprinting, and tandem mass spectrometry were used for protein
      identification. Around 1000 spots were visualized by "blue silver" colloidal
      Coomassie staining in a non-linear pI range from 3 to 10 with high resolution,
      which allowed the identification of 950 proteins (549 different proteins and
      isoforms). Comparison among the cytosolic proteomes of the wild-type NRRL 1951,
      Wisconsin 54-1255 (an improved, moderate penicillin producer), and AS-P-78 (a
      penicillin high producer) strains indicated that global metabolic reorganizations
      occurred during the strain improvement program. The main changes observed in the
      high producer strains were increases of cysteine biosynthesis (a penicillin
      precursor), enzymes of the pentose phosphate pathway, and stress response
      proteins together with a reduction in virulence and in the biosynthesis of other
      secondary metabolites different from penicillin (pigments and isoflavonoids). In
      the wild-type strain, we identified enzymes to utilize cellulose, sorbitol, and
      other carbon sources that have been lost in the high penicillin producer strains.
      Changes in the levels of a few specific proteins correlated well with the
      improved penicillin biosynthesis in the high producer strains. These results
      provide useful information to improve the production of many other bioactive
      secondary metabolites.

PMID- 20154336
TI  - Comprehensive sequence analysis of the human IL23A gene defines new variation
      content and high rate of evolutionary conservation.
AB  - A newly described heterodimeric cytokine, interleukin-23 (IL-23) is emerging as a
      key player in both the innate and the adaptive T helper (Th)17 driven immune
      response as well as an initiator of several autoimmune diseases. The rate
      limiting element of IL-23 production is believed to be driven by expression of
      the unique p19 subunit encoded by IL23A. We set out to perform comprehensive DNA
      sequencing of this previously under-studied gene in 96 individuals from two
      evolutionary distinct human population groups, Southern African Bantu and
      European. We observed a total of 33 different DNA variants within these two
      groups, 22 (67%) of which are currently not reported in any available database.
      We further demonstrate both inter-population and intra-species sequence
      conservation within the coding and known regulatory regions of IL23A, supporting
      a critical physiological role for IL-23. We conclude that IL23A may have
      undergone positive selection pressure directed towards conservation, suggesting
      that functional genetic variants within IL23A will have a significant impact on
      the host immune response.

PMID- 20154337
TI  - Advanced glycation end-products, anti-hypertensive treatment and diastolic
      function in patients with hypertension and diastolic dysfunction.
AB  - AIMS: To investigate the relationship between advanced glycation end-products
      (AGEs) and diastolic function and the response to blood pressure treatment in
      patients with hypertension and diastolic dysfunction. METHODS AND RESULTS: Data
      were analysed from 97 patients (aged 65 +/- 10 years, 36% male) who were randomly
      assigned to 6 months open-label treatment with either eprosartan on top of other
      anti-hypertensive drugs (n = 47) or other anti-hypertensive drugs alone (n = 50).
      Tissue AGE accumulation was measured using a validated skin-autofluorescence
      (skin-AF) reader (n = 26). Plasma N(epsilon)-(carboxymethyl)lysine (CML),
      N(epsilon)-(carboxyethyl)lysine (CEL), and pentosidine were measured by LC-MS/MS
      and HPLC. Diastolic function was assessed using echocardiography. Blood pressure
      was reduced from 157/91 to 145/84 mmHg (P < 0.001) in the eprosartan group and
      from 158/91 to 141/83 mmHg (P < 0.001) in the control group. No effect of
      eprosartan was found on AGE levels. In patients with baseline skin-AF < median,
      E/A ratio (P = 0.04) and the mean peak early-diastolic filling velocity (E')
      improved (P = 0.001). In contrast, in patients with skin-AF levels > median, E/A
      ratio (P = 0.84) and mean E' (P = 0.32) remained unchanged. CONCLUSION: Although
      eprosartan did not decrease levels of AGEs, patients with lower skin-AF at
      baseline showed a larger improvement in diastolic function in response to either
      anti-hypertensive treatment compared with patients with higher skin-AF.

PMID- 20154338
TI  - Quantitative detection of multiple gene promoter hypermethylation in tumor
      tissue, serum, and cerebrospinal fluid predicts prognosis of malignant gliomas.
AB  - Aberrant promoter hypermethylation of several known or putative tumor suppressor
      genes occurs frequently during the malignant transformation in gliomas. We
      hypothesized that quantitative analysis of methylated genes will provide
      prognostic values in malignant glioma patients. We used an immunocapturing
      approach followed by real-time polymerase chain reaction analysis to detect
      altered patterns of promoter methylation in O-6-methylguanine-DNA
      methyltransferase (MGMT), p16INK4a, tissue inhibitor of metalloproteinase-3 (TIMP
      3), and thrombospondin 1 (THBS1). The tumor tissue and paired serum as well as
      cerebrospinal fluid (CSF) from 66 patients with malignant gliomas were studied.
      Serum and CSF from 20 age-matched noncancer individuals were used as control.
      Promoter hypermethylation in MGMT, p16INK4a, TIMP-3, and THBS1 was detected at
      high frequencies in tumor tissue, serum, and CSF. None of the control serum or
      CSF showed aberrant methylation. Hypermethylation in serum and CSF DNA was all
      accompanied with methylation in the corresponding tumor tissues with 100%
      specificity. Highly elevated MGMT, p16INK4a, and THBS1 methylation levels in
      gliomas serum were the sole independent factors predicting inferior overall
      survival in this cohort. For progression-free survival, hypermethylation of MGMT
      and THBS1 in CSF were the independent prognostic factors. Multiple gene promoter
      hypermethylation analysis appears to be promising as a prognostic factor in
      glioma and as a mini-invasive tumor marker in serum and/or CSF DNA. Evaluation of
      these changes may help in selecting glioma patients for optimal adjuvant
      treatments and modifying chemotherapy.

PMID- 20154339
TI  - Plant thymidine kinase 1: a novel efficient suicide gene for malignant glioma
      therapy.
AB  - The prognosis for malignant gliomas remains poor, and new treatments are urgently
      needed. Targeted suicide gene therapy exploits the enzymatic conversion of a
      prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this
      therapeutic strategy has been considered a promising regimen for central nervous
      system (CNS) tumors, several obstacles have been encountered such as inefficient
      gene transfer to the tumor cells, limited prodrug penetration into the CNS, and
      inefficient enzymatic activity of the suicide gene. We report here the cloning
      and successful application of a novel thymidine kinase 1 (TK1) from the tomato
      plant, with favorable characteristics in vitro and in vivo. This enzyme (toTK1)
      is highly specific for the nucleoside analog prodrug zidovudine (azidothymidine,
      AZT), which is known to penetrate the blood-brain barrier. An important feature
      of toTK1 is that it efficiently phosphorylates its substrate AZT not only to AZT
      monophosphate, but also to AZT diphosphate, with excellent kinetics. The
      efficiency of the toTK1/AZT system was confirmed when toTK1-transduced human
      glioblastoma (GBM) cells displayed a 500-fold increased sensitivity to AZT
      compared with wild-type cells. In addition, when neural progenitor cells were
      used as delivery vectors for toTK1 in intracranial GBM xenografts in nude rats,
      substantial attenuation of tumor growth was achieved in animals exposed to AZT,
      and survival of the animals was significantly improved compared with controls.
      The novel toTK1/AZT suicide gene therapy system in combination with stem cell
      mediated gene delivery promises new treatment of malignant gliomas.

PMID- 20154340
TI  - Efficient recovery of dysferlin deficiency by dual adeno-associated vector
      mediated gene transfer.
AB  - Deficiency of the dysferlin protein presents as two major clinical phenotypes:
      limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Dysferlin is known
      to participate in membrane repair, providing a potential hypothesis to the
      underlying pathophysiology of these diseases. The size of the dysferlin cDNA
      prevents its direct incorporation into an adeno-associated virus (AAV) vector for
      therapeutic gene transfer into muscle. To bypass this limitation, we split the
      dysferlin cDNA at the exon 28/29 junction and cloned it into two independent AAV
      vectors carrying the appropriate splicing sequences. Intramuscular injection of
      the corresponding vectors into a dysferlin-deficient mouse model led to the
      expression of full-length dysferlin for at least 1 year. Importantly, systemic
      injection in the tail vein of the two vectors led to a widespread although weak
      expression of the full-length protein. Injections were associated with an
      improvement of the histological aspect of the muscle, a reduction in the number
      of necrotic fibers, restoration of membrane repair capacity and a global
      improvement in locomotor activity. Altogether, these data support the use of such
      a strategy for the treatment of dysferlin deficiency.

PMID- 20154341
TI  - Genome-wide association study of homocysteine levels in Filipinos provides
      evidence for CPS1 in women and a stronger MTHFR effect in young adults.
AB  - Plasma homocysteine (Hcy) level is associated with cardiovascular disease and may
      play an etiologic role in vascular damage, a precursor for atherosclerosis. We
      performed a genome-wide association study for Hcy in 1786 unrelated Filipino
      women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The most
      strongly associated single-nucleotide polymorphism (SNP) (rs7422339, P = 4.7 x
      10(-13)) encodes Thr1405Asn in the gene CPS1 and explained 3.0% of variation in
      the Hcy level. The widely studied MTHFR C677T SNP (rs1801133) was also highly
      significant (P = 8.7 x 10(-10)) and explained 1.6% of the trait variation. We
      also genotyped these two SNPs in 1679 CLHNS young adult offspring. The MTHFR
      C677T SNP was strongly associated with Hcy (P = 1.9 x 10(-26)) and explained
      approximately 5.1% of the variation in the offspring. In contrast, the CPS1
      variant was significant only in females (P = 0.11 in all; P = 0.0087 in females).
      Combined analysis of all samples confirmed that the MTHFR variant was more
      strongly associated with Hcy in the offspring (interaction P = 1.2 x 10(-5)).
      Furthermore, although there was evidence for a positive synergistic effect
      between the CPS1 and MTHFR SNPs in the offspring (interaction P = 0.0046), there
      was no significant evidence for an interaction in the mothers (P = 0.55). These
      data confirm a recent finding that CPS1 is a locus influencing Hcy levels in
      women and suggest that genetic effects on Hcy may differ across developmental
      stages.

PMID- 20154343
TI  - An ovine transgenic Huntington's disease model.
AB  - Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative
      disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin
      (HTT) gene [Huntington's Disease Collaborative Research Group (1993) A novel gene
      containing a trinucleotide repeat that is expanded and unstable on Huntington's
      disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell,
      72, 971-983]. Despite identification of the gene in 1993, the underlying life
      long disease process and effective treatments to prevent or delay it remain
      elusive. In an effort to fast-track treatment strategies for HD into clinical
      trials, we have developed a new large-animal HD transgenic ovine model. Sheep,
      Ovis aries L., were selected because the developmental pattern of the ovine basal
      ganglia and cortex (the regions primarily affected in HD) is similar to the
      analogous regions of the human brain. Microinjection of a full-length human HTT
      cDNA containing 73 polyglutamine repeats under the control of the human promotor
      resulted in six transgenic founders varying in copy number of the transgene.
      Analysis of offspring (at 1 and 7 months of age) from one of the founders showed
      robust expression of the full-length human HTT protein in both CNS and non-CNS
      tissue. Further, preliminary immunohistochemical analysis demonstrated the
      organization of the caudate nucleus and putamen and revealed decreased expression
      of medium size spiny neuron marker DARPP-32 at 7 months of age. It is anticipated
      that this novel transgenic animal will represent a practical model for
      drug/clinical trials and surgical interventions especially aimed at delaying or
      preventing HD initiation. New sequence accession number for ovine HTT mRNA:
      FJ457100.

PMID- 20154342
TI  - Functional conservation of human Spastin in a Drosophila model of autosomal
      dominant-hereditary spastic paraplegia.
AB  - Mutations in spastin are the most frequent cause of the neurodegenerative disease
      autosomal dominant-hereditary spastic paraplegia (AD-HSP). Drosophila
      melanogaster lacking spastin exhibit striking behavioral similarities to human
      patients suffering from AD-HSP, suggesting conservation of Spastin function
      between the species. Consistent with this, we show that exogenous expression of
      wild-type Drosophila or human spastin rescues behavioral and cellular defects in
      spastin null flies equivalently. This enabled us to generate genetically
      representative models of AD-HSP, which arises from dominant mutations in spastin
      rather than a complete loss of the gene. Flies co-expressing one copy of wild
      type human spastin and one encoding the K388R catalytic domain mutation in the
      fly spastin null background, exhibit aberrant distal synapse morphology and
      microtubule distribution, similar to but less severe than spastin nulls. R388 or
      a separate nonsense mutation act dominantly and are furthermore sufficient to
      confer partial rescue, supporting in vitro evidence for additional, non-catalytic
      Spastin functions. Using this model, we tested the observation from human
      pedigrees that S44L and P45Q are trans-acting modifiers of mutations affecting
      the Spastin catalytic domain. As in humans, both L44 and Q45 are largely silent
      when heterozygous, but exacerbate mutant phenotypes when expressed in trans with
      R388. These transgenic 'AD-HSP' flies therefore provide a powerful and tractable
      model to enhance our understanding of the cellular and behavioral consequences of
      human spastin mutations and test hypotheses directly relevant to the human
      disease.

PMID- 20154344
TI  - Onset of peripheral arterial disease: role of endothelin in endothelial
      dysfunction.
AB  - OBJECTIVES: Endothelial dysfunction and inflammation are understood to contribute
      to the onset of peripheral arterial disease (PAD), and endothelin (ET) may play
      an important role in this process. This study investigated the role of ET in PAD,
      and its relationships with symptoms, endothelial dysfunction and inflammation.
      METHODS AND RESULTS: This cross-sectional study enrolled 141 participants: 66
      patients with PAD and intermittent claudication, 37 patients with PAD and
      critical ischemia, and 38 healthy controls aged under 35 years. There were no
      gender distribution differences between control and diseased groups. Moreover, no
      differences were observed in age or cardiovascular risk factors distribution
      between patients with critical ischemia and patients with claudication. Plasma ET
      concentrations were significantly higher in patients vs. controls (8.76+/-77.1
      vs. 6.45+/-0.89 pmol/l, respectively; P=0.002). Nevertheless, patients with
      claudication exhibited significantly higher plasma ET concentrations vs. patients
      with critical ischemia (10.97+/-7.9 vs. 4.82+/-2.57 pmol/l, respectively;
      P<0.001). Otherwise, significantly greater serum concentrations of C-reactive
      protein (CRP) were observed in patients with critical ischemia vs. patients with
      claudication (16.94 vs. 4.73 mg/l, respectively; P=0.001) and controls (0.96
      mg/l; P=0.001). Plasma concentrations of ET had a modest negative correlation
      with serum concentrations of CRP (-0.165; P=0.095). CONCLUSION: Plasma
      concentrations of ET in patients with PAD are greatest in early disease; ET
      concentrations decrease substantially and inflammation arises as disease
      advances. Serum CRP concentrations exhibit a modest negative correlation with
      those of ET.

PMID- 20154345
TI  - Three-dimensional transesophageal echocardiography in Ebstein's anomaly.
AB  - Three-dimensional (3D) transthoracic echocardiography has advantages over
      traditional two-dimensional (2D) echocardiography in visualizing tricuspid valve
      morphology in Ebstein's anomaly. We describe the application of intra-operative
      3D transesophageal echocardiography during a tricuspid valve repair procedure in
      a patient with Ebstein's anomaly. Intra-operatively three-dimensional
      transesophageal echocardiographic (3D TEE) data sets revealed morphology and
      function of the tricuspid valve, right ventricle outflow tract (RVOT) and
      pulmonary valve before and after repair. Tricuspid valve leaflet morphology and
      coaptation as visualized with 3D TEE proved to be consistent with intra-operative
      findings. Analysis of the tricuspid valve, RVOT and pulmonary valve in the multi
      planar review (MPR) mode revealed a bicuspid pulmonary valve, which had not been
      noticed on the preoperative 2D echocardiographic work-up. In this patient with
      Ebstein's anomaly, 3D TEE provided additional information on morphology and
      function of tricuspid valve, RVOT and pulmonary valve.

PMID- 20154346
TI  - Which cannulation (ascending aortic cannulation or peripheral arterial
      cannulation) is better for acute type A aortic dissection surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was 'Which cannulation (ascending aortic
      cannulation or peripheral arterial cannulation) is better for acute type A aortic
      dissection surgery?' Altogether 393 papers were found using the reported search,
      of which 14 represented the best evidence to answer the clinical question. The
      authors, journal, date and country of publication, patient group studied, study
      type, relevant outcomes and results of these papers are tabulated. Femoral artery
      cannulation has the highest rate of mortality, stroke rate and other
      complications including retrograde cerebral embolization, organ malperfusion and
      perfusion of the false lumen. Five out of 14 papers were found to be reporting in
      favour of axillary (or subclavian) artery cannulation over femoral artery
      cannulation. In a total of 1829 patients evaluated in these studies, 1068
      patients demonstrated a significantly lower complication rate with axillary
      artery cannulation than femoral artery cannulation. Some of the larger studies
      showed femoral artery cannulation has higher mortality and stroke rates ranging
      from 6.5% to 40% and 3% to 17%, respectively. Meanwhile, mortality and stroke
      rates were ranging from 3% to 8.6% and 1.75% to 4%, respectively, in the favour
      of axillary artery cannulation. A total of seven studies evaluated direct aortic
      cannulation for the establishment of cardiopulmonary bypass (CPB). They
      demonstrated mortality and stroke rates from 0% to 15% and 3.8% to 21%,
      respectively. Central cannulation has promising results with a lower mortality
      rate but a higher stroke rate. Direct cannulation of the true lumen is a
      promising method for quick and easy establishment of CPB. Axillary artery
      cannulation with a side graft, although it takes more time to construct, is
      proven to be safe and straightforward, with fewer local and systemic
      complications including lower mortality and neurological complications.

PMID- 20154347
TI  - Impact of number and site of lymph node invasion on survival of adenocarcinoma of
      esophagogastric junction.
AB  - Lymph node involvement in adenocarcinoma of the esophagogastric junction (EGJ) is
      similar to that of gastric cancer. The impact on survival of the number and site
      of lymph nodes involved in a subgroup of patients undergone surgery for
      adenocarcinoma of EGJ is reported. Sixty-four patients undergone transthoracic
      esophagectomy with two-field lymphadenectomy for adenocarcinoma of the EGJ were
      retrospectively assessed. Five-year survival according to AJCC gastric cancer
      nodal classification and central node invasion was evaluated. In N0 patients
      survival was assessed in relation to the number of lymph nodes removed. Five-year
      survival was 72% in N0, 46% in N1 and 0% in N2 and N3 group. Intergroup
      differences were statistically significant (P<0.05) except between N2 and N3
      groups. Overall survival was different depending on the infiltration of distal or
      proximal site nodes, 23% vs. 58% (P<0.05); in N0 patients it was related to the
      number of lymph nodes removed (83% >15 vs. 57% <15, P<0.05). Classification of
      lymph node involvement in adenocarcinoma of the EGJ by gastric cancer criteria is
      adequate for prognostic purposes. The involvement of distal nodes in all cases
      and the removal of <15 nodes in N0 group resulted as independent negative
      predictive factors.

PMID- 20154348
TI  - Genetic diversity and population structure in the tomato-like nightshades Solanum
      lycopersicoides and S. sitiens.
AB  - BACKGROUND AND AIMS: Two closely related, wild tomato-like nightshade species,
      Solanum lycopersicoides and Solanum sitiens, inhabit a small area within the
      Atacama Desert region of Peru and Chile. Each species possesses unique traits,
      including abiotic and biotic stress tolerances, and can be hybridized with
      cultivated tomato. Conservation and utilization of these tomato relatives would
      benefit from an understanding of genetic diversity and relationships within and
      between populations. METHODS: Levels of genetic diversity and population genetic
      structure were investigated by genotyping representative accessions of each
      species with a set of simple sequence repeat (SSR) and allozyme markers. KEY
      RESULTS: As expected for self-incompatible species, populations of S.
      lycopersicoides and S. sitiens were relatively diverse, but contained less
      diversity than the wild tomato Solanum chilense, a related allogamous species
      native to this region. Populations of S. lycopersicoides were slightly more
      diverse than populations of S. sitiens according to SSRs, but the opposite trend
      was found with allozymes. A higher coefficient of inbreeding was noted in S.
      sitiens. A pattern of isolation by distance was evident in both species,
      consistent with the highly fragmented nature of the populations in situ. The
      populations of each taxon showed strong geographical structure, with evidence for
      three major groups, corresponding to the northern, central and southern elements
      of their respective distributions. CONCLUSIONS: This information should be useful
      for optimizing regeneration strategies, for sampling of the populations for genes
      of interest, and for guiding future in situ conservation efforts.

PMID- 20154350
TI  - Chronotropic incompetence: a never-ending story.

PMID- 20154349
TI  - Impact of the control of symptomatic paroxysmal atrial fibrillation on health
      related quality of life.
AB  - AIMS: Patients with atrial fibrillation (AF) consider the related symptoms
      disruptive to their quality of life (QoL). This study aimed to evaluate the
      impact of the control of symptomatic paroxysmal AF (PAF) on QoL. METHODS AND
      RESULTS: Patients with symptomatic PAF were treated for 48 weeks with open-label
      flecainide acetate controlled release (Flec CR). Quality of life was assessed by
      SF-36 and Atrial Fibrillation Severity Scale scores at baseline, Week 12 (W12),
      W24, and W48. Of the 229 treated patients, 217 were analysed for QoL (123 with
      controlled and 94 with uncontrolled symptomatic PAF at inclusion). The controlled
      group had a similar or better QoL (SF-36) at baseline compared with a reference
      population (significantly better for: physical functioning, bodily pain, and
      physical component). The uncontrolled group had an inferior QoL (significantly
      worse for: role physical, general health, vitality, role emotional, social
      functioning, mental health, and mental component). When treated with Flec CR, the
      controlled group baseline QoL scores were maintained and the uncontrolled group
      scores were improved to a level comparable to the controlled group scores. Safety
      findings reflect the known clinical safety profile of flecainide acetate.
      CONCLUSION: In this study, patients with uncontrolled symptomatic PAF at baseline
      had an inferior QoL to those with controlled symptomatic PAF. Following treatment
      with controlled-release flecainide acetate, their QoL improved to a level
      comparable to controlled patients.

PMID- 20154351
TI  - Blockade of dopamine activity in the nucleus accumbens impairs learning
      extinction of conditioned fear.
AB  - Three experiments used rats to investigate the role of dopamine activity in
      learning to inhibit conditioned fear responses (freezing) in extinction. In
      Experiment 1, rats systemically injected with the D2 dopamine antagonist,
      haloperidol, froze more across multiple extinction sessions and on a drug-free
      retention test than control rats. In Experiment 2, rats extinguished under an
      intracerebroventricular (ICV) infusion of haloperidol suppressed fear responses
      across extinction but froze more on a subsequent drug-free retention test than
      control rats. In Experiment 3, rats extinguished under an infusion of haloperidol
      in the nucleus accumbens were impaired in suppressing fear responses across
      extinction and froze more on subsequent drug-free retention test than control
      rats. These results show that learning to inhibit fear responses in extinction
      requires dopamine activity in the nucleus accumbens. They were interpreted to
      mean that dopaminergic activity in the nucleus accumbens regulates the prediction
      error required for learning to inhibit fear responses in extinction.

PMID- 20154352
TI  - Synapsin is selectively required for anesthesia-sensitive memory.
AB  - Odor-shock memory in Drosophila melanogaster consists of heterogeneous components
      each with different dynamics. We report that a null mutant for the evolutionarily
      conserved synaptic protein Synapsin entails a memory deficit selectively in early
      memory, leaving later memory as well as sensory motor function unaffected.
      Notably, a consolidated memory component remaining after cold-anesthesia is not
      impaired, suggesting that only anesthesia-sensitive memory [ASM] depends on
      Synapsin. The lack of Synapsin does not further impair the memory deficit of
      mutants for the rutabaga gene encoding the type I adenylyl cyclase. This suggests
      that cAMP signaling, through a Synapsin-dependent mechanism, may underlie the
      formation of a labile memory component.

PMID- 20154353
TI  - Ventral lateral geniculate input to the medial pons is necessary for visual
      eyeblink conditioning in rats.
AB  - The conditioned stimulus (CS) pathway that is necessary for visual delay eyeblink
      conditioning was investigated in the current study. Rats were initially given
      eyeblink conditioning with stimulation of the ventral nucleus of the lateral
      geniculate (LGNv) as the CS followed by conditioning with light and tone CSs in
      separate training phases. Muscimol was infused into the medial pontine nuclei
      (MPN) after each training phase to examine conditioned response (CR) retention to
      each CS. The spread of muscimol infusions targeting the MPN was examined with
      fluorescent muscimol. Muscimol infusions into the MPN resulted in a severe
      impairment in retention of CRs with the LGNv stimulation and light CSs. A less
      severe impairment was observed with the tone CS. The results suggest that CS
      information from the LGNv and light CSs is relayed to the cerebellum through the
      MPN. Retrograde tracing with fluoro-gold (FG) showed that the LGNv and nucleus of
      the optic tract have ipsilateral projections to the MPN. Unilateral inputs to the
      MPN from the LGNv and nucleus of the optic tract may be part of the visual CS
      pathway that is necessary for visual eyeblink conditioning.

PMID- 20154354
TI  - Role of the basolateral amygdala in the reinstatement and extinction of fear
      responses to a previously extinguished conditioned stimulus.
AB  - Four experiments used rats to study the role of the basolateral amygdala (BLA) in
      the reinstatement and extinction of fear responses (freezing) to a previously
      extinguished conditioned stimulus (CS). In Experiment 1, BLA inactivation before
      pairing the extinguished CS with the shock unconditioned stimulus (US) or before
      US-alone exposure impaired the restoration and the reinstatement of fear
      responses to the extinguished CS. In Experiment 2, BLA inactivation before
      extinction impaired long-term inhibition of fear responses, but its inactivation
      before extinction of fear responses restored by CS-US pairing did not impair long
      term inhibition. In Experiment 3, BLA inactivation before extinction of fear
      responses or before the extinction of fear responses reinstated by US-alone
      exposure impaired long-term inhibition. In Experiment 4, BLA inactivation did not
      impair long-term inhibition of fear responses reinstated by US-alone exposure if
      the context where the US-alone exposure occurred had been previously
      extinguished. These results confirm that the BLA is critical for both learning
      fear and fear inhibition, but not for relearning this inhibition. The results are
      consistent with the view that reinstatement is due to the extinguished CS being
      tested in a dangerous context and are discussed in terms of a contemporary neural
      model of fear inhibition.

PMID- 20154355
TI  - Perirhinal cortex is necessary for acquiring, but not for retrieving object-place
      paired association.
AB  - Remembering events frequently involves associating objects and their associated
      locations in space, and it has been implicated that the areas associated with the
      hippocampus are important in this function. The current study examined the role
      of the perirhinal cortex in retrieving familiar object-place paired associates,
      as well as in acquiring novel ones. Rats were required to visit one of two
      locations of a radial-arm maze and choose one of the objects (from a pair of
      different toy objects) exclusively associated with a given arm. Excitotoxic
      lesions of the perirhinal cortex initially impaired the normal retrieval of
      object-place paired-associative memories that had been learned presurgically, but
      the animals relearned gradually to the level of controls. In contrast, when
      required to associate a novel pair of objects with the same locations of the
      maze, the same lesioned rats were severely impaired with minimal learning, if
      any, taking place throughout an extensive testing period. However, the lesioned
      rats were normal in discriminating two different objects presented in a fixed arm
      in the maze. The results suggest that the perirhinal cortex is indispensable to
      forming discrete representations for object-place paired associates. Its role,
      however, may be compensated for by other structures when familiar object-place
      paired associative memories need to be retrieved.

PMID- 20154356
TI  - Recognition memory: adding a response deadline eliminates recollection but spares
      familiarity.
AB  - A current controversy in memory research concerns whether recognition is
      supported by distinct processes of familiarity and recollection, or instead by a
      single process wherein familiarity and recollection reflect weak and strong
      memories, respectively. Recent studies using receiver operating characteristic
      (ROC) analyses in an animal model have shown that manipulations of the memory
      demands can eliminate the contribution of familiarity while sparing recollection.
      Here it is shown that a different manipulation, specifically the addition of a
      response deadline in recognition testing, results in the opposite performance
      pattern, eliminating the contribution of recollection while sparing that of
      familiarity. This dissociation, combined with the earlier findings, demonstrates
      that familiarity and recollection are differentially sensitive to specific memory
      demands, strongly supporting the dual process view.

PMID- 20154357
TI  - Role of amygdala and hippocampus in the neural circuit subserving conditioned
      defeat in Syrian hamsters.
AB  - We examined the roles of the amygdala and hippocampus in the formation of
      emotionally relevant memories using an ethological model of conditioned fear
      termed conditioned defeat (CD). Temporary inactivation of the ventral, but not
      dorsal hippocampus (VH, DH, respectively) using muscimol disrupted the
      acquisition of CD, whereas pretraining VH infusions of anisomycin, a protein
      synthesis inhibitor, failed to block CD. To test for a functional connection
      between the VH and basolateral amygdala (BLA), we used a classic functional
      connectivity design wherein injections are made unilaterally in brain areas
      either on the same or opposite sides of the brain. A functional connection
      between the BLA and VH necessary for the acquisition of CD could not be found
      because unilateral inactivation of either BLA alone (but not either VH alone) was
      sufficient to disrupt CD. This finding suggested instead that there may be a
      critical functional connection between the left and right BLA. In our final
      experiment, we infused muscimol unilaterally in the BLA and assessed Fos
      immunoreactivity on the contralateral side following exposure to social defeat.
      Inactivation of either BLA significantly reduced defeat-induced Fos
      immunoreactivity in the contralateral BLA. These experiments demonstrate for the
      first time that whereas the VH is necessary for the acquisition of CD, it does
      not appear to mediate the plastic changes underlying CD. There also appears to be
      a critical interaction between the two BLAs such that bilateral activation of
      this brain area must occur in order to support fear learning in this model, a
      finding that is unprecedented to date.

PMID- 20154358
TI  - Assessment of the role of MAP kinase in mediating activity-dependent
      transcriptional activation of the immediate early gene Arc/Arg3.1 in the dentate
      gyrus in vivo.
AB  - Different physiological and behavioral events activate transcription of
      Arc/Arg3.1 in neurons in vivo, but the signal transduction pathways that mediate
      induction in particular situations remain to be defined. Here, we explore the
      relationships between induction of Arc/Arg3.1 transcription in dentate granule
      cells in vivo and activation of mitogen-activated protein (MAP) kinase as
      measured by extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation. We show
      that ERK1/2 phosphorylation is strongly induced in dentate granule cells within
      minutes after induction of perforant path long-term potentiation (LTP). Phospho
      ERK staining appears in nuclei within minutes after stimulation commences, and
      ERK phosphorylation returns to control levels within 60 min. Electroconvulsive
      seizures, which strongly induce prolonged Arc/Arg3.1 transcription in dentate
      granule cells, induced ERK1/2 phosphorylation in granule cells that returned to
      control levels within 30 min. Following 30, 60, and 120 min of exploration in a
      novel complex environment, Arc/Arg3.1 transcription was activated in many more
      granule cells than stained positively for p-ERK at all time points. Although
      Arc/Arg3.1 transcription was induced in most pyramidal neurons in CA1 following
      exploration, very few pyramidal neurons exhibited nuclear p-ERK1/2 staining.
      Local delivery of U0126 during the induction of perforant path LTP blocked
      transcriptional activation of Arc/Arg3.1 in a small region near the injection
      site and blocked Arc/Arg3.1 protein expression over a wider region. Our results
      indicate that activation of Arc/Arg3.1 transcription in dentate granule cells in
      vivo is mediated in part by MAP kinase activation, but other signaling pathways
      also contribute, especially in the case of Arc/Arg3.1 induction in response to
      experience.

PMID- 20154359
TI  - Protein complex of Drosophila ATRX/XNP and HP1a is required for the formation of
      pericentric beta-heterochromatin in vivo.
AB  - ATRX belongs to the family of SWI2/SNF2-like ATP-dependent nucleosome remodeling
      molecular motor proteins. Mutations of the human ATRX gene result in a severe
      genetic disorder termed X-linked alpha-thalassemia mental retardation (ATR-X)
      syndrome. Here we perform biochemical and genetic analyses of the Drosophila
      melanogaster ortholog of ATRX. The loss of function allele of the Drosophila
      ATRX/XNP gene is semilethal. Drosophila ATRX is expressed throughout development
      in two isoforms, p185 and p125. ATRX185 and ATRX125 form distinct multisubunit
      complexes in fly embryo. The ATRX185 complex comprises p185 and heterochromatin
      protein HP1a. Consistently, ATRX185 but not ATRX125 is highly concentrated in
      pericentric beta-heterochromatin of the X chromosome in larval cells. HP1a
      strongly stimulates biochemical activities of ATRX185 in vitro. Conversely,
      ATRX185 is required for HP1a deposition in pericentric beta-heterochromatin of
      the X chromosome. The loss of function allele of the ATRX/XNP gene and mutant
      allele that does not express p185 are strong suppressors of position effect
      variegation. These results provide evidence for essential biological functions of
      Drosophila ATRX in vivo and establish ATRX as a major determinant of pericentric
      beta-heterochromatin identity.

PMID- 20154361
TI  - Inflammation and insulin resistance induced by trans-10, cis-12 conjugated
      linoleic acid depend on intracellular calcium levels in primary cultures of human
      adipocytes.
AB  - We previously demonstrated that trans-10, cis-12 (10,12) conjugated linoleic acid
      (CLA) induced inflammation and insulin resistance in primary human adipocytes by
      activating nuclear factor kappaB (NFkappaB) and extracellular signal-related
      kinase (ERK) signaling. In this study, we demonstrated that the initial increase
      in intracellular calcium ([Ca2+]i) mediated by 10,12 CLA was attenuated by TMB-8,
      an inhibitor of calcium release from the endoplasmic reticulum (ER), by BAPTA, an
      intracellular calcium chelator, and by D609, a phospholipase C (PLC) inhibitor.
      Moreover, BAPTA, TMB-8, and D609 attenuated 10,12 CLA-mediated production of
      reactive oxygen species (ROS), activation of ERK1/2 and cJun-NH2-terminal kinase
      (JNK), and induction of inflammatory genes. 10,12 CLA-mediated binding of
      NFkappaB to the promoters of interleukin (IL)-8 and cyclooxygenase (COX)-2 and
      induction of calcium-calmodulin kinase II (CaMKII) beta were attenuated by TMB-8.
      KN-62, a CaMKII inhibitor, also suppressed 10,12 CLA-mediated ROS production and
      ERK1/2 and JNK activation. Additionally, KN-62 attenuated 10,12 CLA induction of
      inflammatory and integrated stress response genes, increase in prostaglandin
      F2alpha, and suppression of peroxisome proliferator activated receptor gamma
      protein levels and insulin-stimulated glucose uptake. These data suggest that
      10,12 CLA increases inflammation and insulin resistance in human adipocytes, in
      part by increasing [Ca2+]i levels, particularly calcium from the ER.

PMID- 20154362
TI  - Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid
      droplet formation in human adipocytes.
AB  - Both insulin and the cell death-inducing DNA fragmentation factor-alpha-like
      effector (CIDE) family play important roles in apoptosis and lipid droplet
      formation. However, regulation of the CIDE family by insulin and the contribution
      of the CIDE family to insulin actions remain unclear. Here, we investigated
      whether insulin regulates expression of the CIDE family and which subtypes
      contribute to insulin-induced anti-apoptosis and lipid droplet formation in human
      adipocytes. Insulin decreased CIDEA and increased CIDEC but not CIDEB mRNA
      expression. Starvation-induced apoptosis in adipocytes was significantly
      inhibited when insulin decreased the CIDEA mRNA level. Small interfering RNA
      mediated depletion of CIDEA inhibited starvation-induced apoptosis similarly to
      insulin and restored insulin deprivation-reduced adipocyte number, whereas CIDEC
      depletion did not. Lipid droplet size of adipocytes was increased when insulin
      increased the CIDEC mRNA level. In contrast, insulin-induced enlargement of lipid
      droplets was markedly abrogated by depletion of CIDEC but not CIDEA. Furthermore,
      depletion of CIDEC, but not CIDEA, significantly increased glycerol release from
      adipocytes. These results suggest that CIDEA and CIDEC are novel genes regulated
      by insulin in human adipocytes and may play key roles in the effects of insulin,
      such as anti-apoptosis and lipid droplet formation.

PMID- 20154363
TI  - Fanconi syndrome in lymphoma patients: report of the first case series.
AB  - BACKGROUND: Fanconi syndrome (FS) is a generalized transport defect in the
      proximal renal tubule leading to renal losses of phosphate, calcium, uric acid,
      bicarbonates as well as glucose, amino acids and other organic compounds. It is
      caused by inherited or acquired disorders including low mass or high mass
      multiple myeloma. OBJECTIVES: To report the first case series of patients with
      lymphoma and FS. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Patients with
      lymphoma and FS were identified in the nephrology department of two teaching
      hospitals in Paris, France and Ghent, Belgium. FS was defined by the presence of
      at least three out of the four following criteria: hypophosphataemia, metabolic
      acidosis, normoglycaemic glucosuria and hypokalaemia. Patients files were
      reviewed and relevant data were collected. RESULTS: Eight patients with lymphoma
      and FS were identified. In six patients, the lymphoma was of the acute T cell
      leukaemia/lymphoma (ATLL) type, related to human T cell lymphotropic virus 1
      (HTLV1) infection. In all patients, FS was severe requiring supplementation. A
      kidney biopsy performed in a patient with post-transplantation primary renal
      lymphoma disclosed intense proximal tubule infiltration by lymphomatous cells. In
      one patient with ATLL, FS features regressed following the successful treatment
      of lymphoma. CONCLUSION: Patients with lymphoma require careful monitoring for
      features of FS; lymphoma should also be added to the spectrum of disorders
      associated to FS. Prospective studies are needed to ascertain the implication of
      HTLV1 in the genesis of FS.

PMID- 20154364
TI  - BMP-7 stops TGF-{beta} in peritoneal fibrosis.

PMID- 20154365
TI  - Impact of restrictive fluid balance focused to increase lung procurement on renal
      function after kidney transplantation.
AB  - BACKGROUND: Restrictive management of fluid status has been proposed to increase
      the rates of lung grafts available for transplant. However, no studies have
      supported the effect of this negative fluid balance in the kidney graft
      recipients. METHODS: We evaluated the effect of restrictive fluid balance in
      brain-dead donors and their impact in 404 kidney recipients using Kaplan-Meier
      curves and Cox regression for long-term effects, and logistic regression for
      short-term effects. Our primary interest was graft survival and the second was
      occurrence of delayed graft function (DGF). RESULTS: A negative or equalized
      fluid balance with a central venous pressure (CVP) <6 mm Hg affects neither graft
      survival in kidney recipients (P = 0.983) nor the development of DGF (P = 0.573).
      A positive fluid balance between brain death and organ retrieval does not reduce
      either the risk of graft survival or the risk of DGF. CONCLUSION: We concluded
      that restrictive management of fluid balance in a multiorgan donor supports
      adequate perfusion to vital organ systems even with a CVP <6 mm Hg. A strict
      fluid balance could avoid volume overload and lung neurogenic oedema, increasing
      the rate of lung grafts available for transplant without impacting either kidney
      graft survival or DGF development.

PMID- 20154366
TI  - pH-induced fabrication of DNA/chitosan/alpha-ZrP nanocomposite and DNA release.
AB  - With positively charged chitosan as an intermediary, herring sperm DNA was
      intercalated into the interlayer galleries of negatively charged alpha-ZrP to
      form DNA/chitosan/alpha-ZrP ternary hybrids at pH 5.5. Fourier-transform IR, x
      ray diffraction and scanning electron microscopy confirmed not only the
      coexistence of DNA, chitosan and alpha-ZrP in the composite but also the layered
      composite structure with an interlayer distance of 4.25 nm. Circular dichroism
      (CD) and UV spectroscopic studies disclosed that the restraint of DNA by the
      layered alpha-ZrP favors stabilization of the double-helical conformation of DNA
      and enhances the denaturation temperature. The intercalated DNA can be
      effectively released from the ternary nanocomposites at pHs higher than 6.5, and
      the released DNA displayed a similar CD spectrum to that of free DNA. The current
      research displays the promising potential to obtain a non-viral gene vector by
      intercalating DNA into negatively charged inorganic layered materials in the
      presence of a positively charged intermediary.

PMID- 20154367
TI  - Electrical characterization of strained and unstrained silicon nanowires with
      nickel silicide contacts.
AB  - We present electrical characterization of nickel monosilicide (NiSi) contacts
      formed on strained and unstrained silicon nanowires (NWs), which were fabricated
      by top-down processing of initially As(+) implanted and activated strained and
      unstrained silicon-on-insulator (SOI) substrates. The resistivity of doped Si NWs
      and the contact resistivity of the NiSi to Si NW contacts are studied as
      functions of the As(+) ion implantation dose and the cross-sectional area of the
      wires. Strained silicon NWs show lower resistivity for all doping concentrations
      due to their enhanced electron mobility compared to the unstrained case. An
      increase in resistivity with decreasing cross section of the NWs was observed for
      all implantation doses. This is ascribed to the occurrence of dopant
      deactivation. Comparing the silicidation of uniaxially tensile strained and
      unstrained Si NWs shows no difference in silicidation speed and in contact
      resistivity between NiSi/Si NW. Contact resistivities as low as 1.2 x 10(-8)
      Omega cm(-2) were obtained for NiSi contacts to both strained and unstrained Si
      NWs. Compared to planar contacts, the NiSi/Si NW contact resistivity is two
      orders of magnitude lower.

PMID- 20154368
TI  - Nonlinear vibrational analysis of single-layer graphene sheets.
AB  - Recent experiments have shown the applicability of single-layer graphene sheets
      (SLGSs) as electromechanical resonators. Existing theoretical models, based on
      linear continuum or atomistic methods, are limited to the study of linear
      vibrations of SLGSs. Here we introduce a hybrid atomistic-structural element
      which is capable of modelling nonlinear behaviour of graphene sheets. This hybrid
      element is based on an empirical inter-atomic potential function and can model
      the nonlinear dynamic response of SLGSs. Using this element, nonlinear
      vibrational analysis of SLGSs is performed. It is shown that the nonlinear
      vibrational analysis of SLGSs predicts significantly higher fundamental
      frequencies. Also, the effects of vibration amplitude as well as the geometry of
      the SLGSs on the fundamental frequency are studied and predictive relations
      between the fundamental frequency, the SLGS length and the non-dimensional
      vibration amplitude are presented. The results are verified with experimental
      observations and are in remarkable agreement.

PMID- 20154369
TI  - Nitrogen doping of nanoporous WO3 layers by NH3 treatment for increased visible
      light photoresponse.
AB  - Nanoporous WO(3) layers were grown by electrochemical anodization of W in a
      fluoride containing electrolyte. These layers were exposed to a thermal treatment
      in NH(3) to achieve nitrogen doping of the material. The morphology, crystal
      structure, composition and photoresponse of pure and nitrogen doped WO(3) were
      compared using scanning electron microscopy, x-ray diffraction, x-ray
      photoelectron spectroscopy, and photoelectrochemical measurements. The results
      clearly show that successful nitrogen doping into WO(3) layers can be achieved by
      controlling the temperature and time during the NH(3) treatment. Most
      importantly, it is demonstrated that for the nitrogen doped WO(3) layers the
      photocurrent is significantly enhanced in the visible light region.

PMID- 20154370
TI  - Batch-processed carbon nanotube wall as pressure and flow sensor.
AB  - A pressure and flow sensor based on the electrothermal-thermistor effect of a
      batch-processed carbon nanotube wall (CNT wall) is presented. The negative
      temperature coefficient of resistance (TCR) of CNTs and the temperature dependent
      tunneling rate through the CNT/silicon junction enable vacuum pressure and flow
      velocity sensing because the heat transfer rate between CNTs and the surrounding
      gas molecules differs depending on pressure and flow rate. The CNT walls are
      synthesized by thermal chemical vapor deposition (CVD) on an array of
      microelectrodes fabricated on a silicon-on-insulator (SOI) wafer. The CNTs are
      self-assembled between the microelectrodes and substrate across the thickness of
      a buried oxide layer during the synthesis process, and the simple batch
      fabrication results in high throughput and yield. A wide pressure range, down to
      3 x 10(-3) from 10(5) Pa, and a nitrogen flow velocity range between 1 and 52.4
      mm s(-1), are sensed. Further experimental characterizations of the bias voltage
      dependent response of the sensor as a vacuum pressure gauge are presented.

PMID- 20154371
TI  - Biological evaluation of layered double hydroxides as efficient drug vehicles.
AB  - Recently there has been a rapid expansion of the development of bioinorganic
      hybrid systems for safe drug delivery. Layered double hydroxides (LDH), a variety
      of available inorganic matrix, possess great promise for this purpose. In this
      study, an oxidative stress biomarker system, including measurement of reactive
      oxygen species, glutathione content, endogenous nitric oxide, carbonyl content in
      proteins, DNA strand breaks and DNA-protein crosslinks, was designed to evaluate
      the biocompatibility of different concentrations of nano-Zn/Al-LDH with a Hela
      cell line. The drug delivery activity of the LDH-folic-acid complex was also
      assessed. The resulting data clearly demonstrated that nano-LDH could be applied
      as a relatively safe drug vehicle with good delivery activity, but with the
      caveat that the effects of high dosages observed here should not be ignored when
      attempting to maximize therapeutic activity by increasing LDH concentration.

PMID- 20154372
TI  - Synthesis of boron nitride nanotubes by boron ink annealing.
AB  - Ball-milling and annealing is one effective method for the mass production of
      boron nitride nanotubes (BNNTs). We report that the method has been modified to a
      boron (B) ink annealing method. In this new process, the nanosize ball-milled B
      particles are mixed with metal nitrate in ethanol to form an ink-like solution,
      and then the ink is annealed in nitrogen-containing gas to form nanotubes. The
      new method greatly enhances the yield of BNNTs, giving a higher density of
      nanotubes. These improvements are caused by the addition of metal nitrate and
      ethanol, both of which can strongly boost the nitriding reaction, as revealed by
      thermogravimetric analysis. The size and structure of BNNTs can be controlled by
      varying the annealing conditions. This high-yield production of BNNTs in large
      quantities enables the large-scale application of BNNTs.

PMID- 20154373
TI  - Dynamic synergy of graphitic nanoplatelets and multi-walled carbon nanotubes in
      polyetherimide nanocomposites.
AB  - Hybridizing graphitic nanoplatelets (GNP) with commercially functionalized multi
      walled carbon nanotubes (MWCNTs) in a polyetherimide (PEI) composite at a total
      loading of 0.5 wt% resulted in considerable improvements in electrical
      conductivity, thermal conductivity and dynamic mechanical properties, compared to
      solely GNP or solely MWCNT composites at the same total loading. The results
      reveal a synergistic interaction between the GNPs and MWCNTs based on GNP
      protection against fragmentation of the MWCNTs during high power sonication,
      while still allowing full dispersion of both fillers, by providing a shielding
      mechanism against MWCNT damage during dispersion processing. A new process for
      molecular level dispersion of exfoliated GNPs in PEI is also reported. Field
      emission scanning electron microscopy revealed strong interactions between PEI
      and the flat surfaces of GNPs and effectively intercalated GNP morphology within
      the matrix. GNPs alone can also produce excellent electrical conductivity
      improvements: at 1.0 wt% of GNP, electrical conductivity of the composite
      increased by 11 orders of magnitude and the percolation threshold was determined
      to be between 0.5 and 1.0 wt% of GNP.

PMID- 20154374
TI  - Metal-modified and vertically aligned carbon nanotube sensors array for landfill
      gas monitoring applications.
AB  - Vertically aligned carbon nanotube (CNT) layers were synthesized on Fe-coated low
      cost alumina substrates using radio-frequency plasma enhanced chemical vapour
      deposition (RF-PECVD) technology. A miniaturized CNT-based gas sensor array was
      developed for monitoring landfill gas (LFG) at a temperature of 150 degrees C.
      The sensor array was composed of 4 sensing elements with unmodified CNT, and CNT
      loaded with 5 nm nominally thick sputtered nanoclusters of platinum (Pt),
      ruthenium (Ru) and silver (Ag). Chemical analysis of multicomponent gas mixtures
      constituted of CO(2), CH(4), H(2), NH(3), CO and NO(2) has been performed by the
      array sensor responses and pattern recognition based on principal component
      analysis (PCA). The PCA results demonstrate that the metal-decorated and
      vertically aligned CNT sensor array is able to discriminate the NO(2) presence in
      the multicomponent mixture LFG. The NO(2) gas detection in the mixture LFG was
      proved to be very sensitive, e.g.: the CNT:Ru sensor shows a relative change in
      the resistance of 1.50% and 0.55% for NO(2) concentrations of 3.3 ppm and 330 ppb
      dispersed in the LFG, respectively, with a wide NO(2) gas concentration range
      measured from 0.33 to 3.3 ppm, at the sensor temperature of 150 degrees C. The
      morphology and structure of the CNT networks have been characterized by scanning
      electron microscopy (SEM), transmission electron microscopy (TEM) and Raman
      spectroscopy. A forest-like nanostructure of vertically aligned CNT bundles in
      the multi-walled form appeared with a height of about 10 microm and a single-tube
      diameter varying in the range of 5-35 nm. The intensity ratio of the Raman
      spectroscopy D-peak and G-peak indicates the presence of disorder and defects in
      the CNT networks. The size of the metal (Pt, Ru, Ag) nanoclusters decorating the
      CNT top surface varies in the range of 5-50 nm. Functional characterization based
      on electrical charge transfer sensing mechanisms in the metal-modified CNT
      chemoresistor array demonstrates high sensitivity by providing minimal sub-ppm
      level detection, e.g., download up to 100 ppb NO(2), at the sensor temperature of
      150 degrees C. The gas sensitivity of the CNT sensor array depends on operating
      temperature, showing a lower optimal temperature of maximum sensitivity for the
      metal-decorated CNT sensors compared to unmodified CNT sensors. Results indicate
      that the recovery mechanisms in the CNT chemiresistors can be altered by a rapid
      heating pulse from room temperature to about 110 degrees C. A comparison of the
      NO(2) gas sensitivity for the chemiresistors based on disorderly networked CNTs
      and vertically aligned CNTs is also reported. Cross-sensitivity towards relative
      humidity of the CNT sensors array is investigated. Finally, the sensing
      properties of the metal-decorated and vertically aligned CNT sensor arrays are
      promising to monitor gas events in the LFG for practical applications with low
      power consumption and moderate sensor temperature.

PMID- 20154375
TI  - Spatially resolved Raman spectroscopy on indium-catalyzed core-shell germanium
      nanowires: size effects.
AB  - The structure of indium-catalyzed germanium nanowires is investigated by atomic
      force microscopy, scanning confocal Raman spectroscopy and transmission electron
      microscopy. The nanowires are formed by a crystalline core and an amorphous
      shell. We find that the diameter of the crystalline core varies along the
      nanowire, down to few nanometers. Phonon confinement effects are observed in the
      regions where the crystalline region is the thinnest. The results are consistent
      with the thermally insulating behavior of the core-shell nanowires.

PMID- 20154377
TI  - Morphology control of a polythiophene-fullerene bulk heterojunction for
      enhancement of the high-temperature stability of solar cell performance by a new
      donor-acceptor diblock copolymer.
AB  - A well defined diblock copolymer (P3HT-b-C(60)) based on regioregular poly(3
      hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) was
      synthesized via two controlled polymerization steps and used as a compatibilizer
      for the P3HT/PCBM blend, which has widely been used as an active layer in bulk
      heterojunction polymer solar cells. The addition of a small amount of P3HT-b
      C(60) results in not only the reduction of phase size of P3HT/PCBM blend but also
      the suppression of macrophase separation for long-time thermal annealing owing to
      the preferential location of the diblock copolymers at the interface between P3HT
      and PCBM phases. The morphology change with the annealing time is closely related
      to the change of the power conversion efficiency (PCE) of solar cells: the PCE of
      P3HT/PCBM greatly decreases with increasing annealing time while the addition of
      P3HT-b-C(60) significantly reduces the decrease of PCE for long-time thermal
      annealing.

PMID- 20154378
TI  - Size-controlled growth of colloidal gold nanoplates and their high-purity
      acquisition.
AB  - A facile while flexible approach to size-controllable high-purity colloidal gold
      nanoplates has been presented. By adjusting the quantity of seeds and I(-)
      through a seed-mediated, cetyltrimethylammonium bromide (CTABr)-assisted
      synthetic system, the edge length of the gold nanoplates can be adjusted from 140
      to 30 nm without changing their thickness or crystal structure. By simply
      increasing the ion concentration of the reaction solution, the as-prepared gold
      nanoplates can be deposited due to the different electrostatic aggregation
      effects between nanoplates and spherical nanoparticles. Effective storage methods
      to keep the structural and optical stability of these gold nanoplates are also
      proposed.

PMID- 20154376
TI  - Nanoconjugated vancomycin: new opportunities for the development of anti-VRSA
      agents.
AB  - More than 90% of Staphylococcus strains are resistant to penicillin. In 1961 S.
      aureus developed resistance to methicillin (MRSA), invalidating almost all
      antibiotics, including the most potent beta-lactams. Vancomycin, a glycopeptide
      antibiotic, was used for the treatment of MRSA in 1980. Vancomycin inhibits the
      bio-synthesis of peptidoglycan and the assembly of NAM-NAG-polypeptide into the
      growing peptidoglycan chain. Vancomycin resistant S. aureus (VRSA) first appeared
      in the USA in 2002. Folic acid tagged chitosan nanoparticles are used as Trojan
      horses to deliver vancomycin into bacterial cells. These nanoparticles are
      biocompatible and biodegradable semisynthetic polymers. These nanosized vehicles
      enhance the transport of vancomycin across epithelial surfaces and show its
      efficient drug action, which has been understood from studies of the minimum
      inhibitory concentration and minimum bactericidal concentration of nanoparticles
      of a chitosan derivative loaded with vancomycin. Tolerance values distinctly show
      that vancomycin loaded into nanoconjugate is very effective and has a strong
      bactericidal effect on VRSA.

PMID- 20154379
TI  - Multi-walled carbon nanotubes affect drug transport across cell membrane in rat
      astrocytes.
AB  - The impact of carbon nanotubes on the cell membrane is an aspect of particular
      importance and interest in the study of carbon nanotubes' interactions with
      living systems. One of the many functions of the cell membrane is to execute
      substance transport into and out of the cell. We investigated the influence of
      multi-walled carbon nanotubes (MWCNTs) on the transport of several compounds
      across in the cell membrane of rat astrocytes using flow cytometry. These
      compounds are fluorescein diacetate, carboxyfluorescein diacetate, rhodamine 123
      and doxorubicin, which are prosubstrate/substrates of multidrug transporter
      proteins. Results showed that MWCNTs significantly inhibited cellular uptake of
      doxorubicin but not the other drugs and the mode of loading made a significant
      difference in doxorubicin uptake. Retention of fluorescein, carboxyfluorescein
      and rhodamine 123 was remarkably higher in MWCNT-exposed cells after an efflux
      period. A kinetics study also demonstrated slower efflux of intracellular
      fluorescein and rhodamine 123. Data presented in this paper suggest that MWCNTs
      could affect drug transport across cell membranes. The implications of the
      findings are discussed.

PMID- 20154380
TI  - Combination of adenovirus and cross-linked low molecular weight PEI improves
      efficiency of gene transduction.
AB  - Recombinant adenovirus (Ad)-mediated gene therapy is an exciting novel strategy
      in cancer treatment. However, poor infection efficiency with coxsackievirus and
      adenovirus receptor (CAR) down-regulated cancer cell lines is one of the major
      challenges for its practical and extensive application. As an alternative method
      of viral gene delivery, a non-viral carrier using cationic materials could
      compensate for the limitation of adenovirus. In our study, adenovectors were
      complexed with a new synthetic polymer PEI-DEG-bis-NPC (PDN) based on
      polyethylenimine (PEI), and then the properties of the vehicle were characterized
      by measurement of size distribution, zeta potential and transmission electron
      microscopy (TEM). Enhancement of gene transduction by Ad/PDN complexes was
      observed in both CAR-overexpressing cell lines (A549) and CAR-lacking cell lines
      (MDCK, CHO, LLC), as a result of facilitating binding and cell uptake of
      adenoviral particles by the cationic component. Ad/PDN complexes also promoted
      the inhibition of tumor growth in vivo and prolonged the survival time of tumor
      bearing mice. These data suggest that a combination of viral and non-viral gene
      delivery methods may offer a new approach to successful cancer gene therapy.

PMID- 20154381
TI  - Probing polymer deformation profiles at varying depths in nanoimprint
      lithography.
AB  - We use immiscible polystyrene (PS)/polyacrylic acid (PAA) bilayer films as resist
      materials for nanoimprint lithography to probe the deformation profiles of the
      resist after the cavity filling process. By systematically varying the
      composition of the bilayers, we determined the deformation profiles of the
      bilayer resists at different depths after filling the 240 and 480 nm wide
      cavities. A single-peak deformation mode was observed for the bilayer films when
      the thickness of the top PS layer is less than the minimum thickness (H(c))
      needed to completely fill the cavities. This is in good agreement with
      simulations based on pressure-driven viscous flow. However, for bilayers with a
      PS layer thickness close to H(c), a dual-peak deformation mode was observed near
      the entrance of the cavities, which is attributed to the stronger shear thinning
      of the polymer resist around these corners.

PMID- 20154382
TI  - Step-and-repeat process for thermal nanoimprint lithography.
AB  - We present a step-and-repeat process for thermal nanoimprint lithography. For the
      selective heating and imprinting, a spin-coated polystyrene layer is exposed to
      infra-red rays from a halogen lamp (intensity approximately 500 W) with a metal
      covered glass while pressed with a transparent polymer mold (Young's modulus
      approximately 300 MPa) under a pressure of approximately 4 bar for 60-120 s.
      During imprinting, the non-irradiated region is protected by a metal screen and a
      heat sink consisting of a copper block at the bottom which prevents the pattern
      collapse by lateral heat conduction from the irradiated region.

PMID- 20154383
TI  - Gold hybrid nanoparticles for targeted phototherapy and cancer imaging.
AB  - Gold and iron oxide hybrid nanoparticles (HNPs) synthesized by the thermal
      decomposition technique are bio-functionalized with a single chain antibody,
      scFv, that binds to the A33 antigen present on colorectal cancer cells. The HNP
      scFv conjugates are stable in aqueous solution with a magnetization value of 44
      emu g(-1) and exhibit strong optical absorbance at 800 nm. Here we test this
      material in targeting, imaging and selective thermal killing of colorectal cancer
      cells. Cellular uptake studies showed that A33-expressing cells take up the
      A33scFv-conjugated HNPs at a rate five times higher than cells that do not
      express the A33 antigen. Laser irradiation studies showed that approximately 53%
      of the A33-expressing cells exposed to targeted HNPs are killed after a six
      minute laser treatment at 5.1 W cm(-2) using a 808 nm continuous wave laser diode
      while < 5% of A33-nonexpressing cells are killed. At a higher intensity, 31.5 W
      cm(-2), the thermal destruction increases to 99 and 40% for A33-expressing cells
      and A33 nonexpressing cells, respectively, after 6 min exposure. Flow cytometric
      analyses of the laser-irradiated A33 antigen-expressing cells show apoptosis
      related cell death to be the primary mode of cell death at 5.1 W cm(-2), with
      increasing necrosis-related cell death at higher laser power. These results
      suggest that this new class of bio-conjugated hybrid nanoparticles can
      potentially serve as an effective antigen-targeted photothermal therapeutic agent
      for cancer treatment as well as a probe for magnetic resonance-based imaging.

PMID- 20154384
TI  - Influencing factors in the occurrence of injured coliforms in the drinking water
      distribution system in the city of La Plata, Argentina.
AB  - The objective of this study was to evaluate the influencing factors in the
      occurrence of coliforms in the drinking water in La Plata (Argentina) from June
      1999 to June 2001. A total of 180 samples were collected from Rio de La Plata
      (102 samples) and Puelche Aquifer (78 samples); 45 samples were collected for
      each of the four seasons. The membrane filter procedure was used for isolating
      bacteria, and each sample was tested for chlorine and pH. The highest percentage
      of samples positive for coliforms in the two tested media was obtained in summer
      while the highest percentage of negative samples was obtained in winter. No
      Escherichia coli was isolated. The percentage of injured coliforms fluctuated
      between 70 and 100%. The most frequently isolated bacteria was Enterobacter
      cloacae in summer, Enterobacter agglomerans in autumn and Klebsiella oxytoca in
      winter and spring. Significant correlations were observed between coliforms and
      the distance from the initial treatment point, and with the level of free
      chlorine. We conclude that drinking water contamination in La Plata occurs in the
      distribution system due to increased temperatures and reduced disinfectant
      levels, which result in bacterial regrowth.

PMID- 20154385
TI  - Evaluating a composite cartridge for small system drinking water treatment.
AB  - A pilot-scale evaluation was conducted at the U.S. Environmental Protection
      Agency (EPA) Test & Evaluation (T&E) Facility in Cincinnati, Ohio, on a multi
      layer, cartridge-based system that combines physical filtration with carbon
      adsorption and ultraviolet (UV) light disinfection to serve as a home-base water
      treatment security device against accidental or intentional contaminant events.
      The system was challenged with different levels of turbidity, a number of
      biological contaminants including Bacillus subtilis, Escherichia coli, MS2
      bacteriophage and Polystyrene Latex (PSL) beads as a surrogate for
      Cryptosporidium and a number of chemical contaminants including super
      chlorination, methyl tertiary butyl ether (MTBE), water chlorination disinfection
      byproducts (DBPs) and diazinon. The results demonstrated that the performance of
      the system varies as a function of the specific contaminant or surrogate. The
      overall performance indicated the potential of the system to improve the quality
      and safety of household water and to serve as an additional treatment barrier in
      circumstances where there is little or no treatment or where the quality of
      treated water may have deteriorated during distribution. The results also
      demonstrated that B. subtilis spore can serve as a more conservative surrogate
      for Cryptosporidium than PSL beads.

PMID- 20154386
TI  - Rainwater harvesting: quality assessment and utilization in The Netherlands.
AB  - The use of roof-collected rainwater as a freely available and sustainable
      alternative to drinking water produced by drinking water companies increases
      worldwide. Initially, rainwater is free of microbial contamination, but it may
      become contaminated by animals and humans or, alternatively, human pathogens may
      grow in stored rainwater resulting in a significant human health risk from
      infectious diseases. This three-year study demonstrated that rainwater stored in
      different reservoirs in The Netherlands was frequently faecally contaminated and
      incidentally contained potential human pathogens such as Campylobacter,
      Cryptosporidium, Giardia, Aeromonas hydrophila and Legionella. Analysis of
      samples during a period with variable weather conditions showed a correlation
      between rainfall intensity and faecal indicator counts and increased detection of
      pathogens after heavy rainfall incidents. Outside temperature had a limited
      effect on both the temperature and the microbiological quality of the water in
      the reservoirs, which did not comply with Dutch drinking water legislation and
      should thus not be consumed without treatment. In general, a health risk may
      arise from exposure to pathogens when contaminated droplets are inhaled, ingested
      or come into contact with the skin. Health risks may be reduced by regular
      cleaning of the collection, storage and transport means, but to assess their
      efficacy field intervention studies are required.

PMID- 20154387
TI  - The quality of drinking water stored in canteens of field soldiers as a potential
      source of enteric diseases.
AB  - Israel Defense Forces (IDF) guidelines for drinking water require the use of
      water only from sources that have been inspected and authorized by a medical
      expert. This study aimed to compare canteen water quality of two military units
      (infantry and armoured corps), to search for sources of possible microbial
      contamination and to look for any impact on gastrointestinal symptoms.
      Statistical analysis revealed that canteens of armoured corp soldiers were
      significantly more contaminated compared to those of infantry soldiers. Outdoor
      taps and water in trailers were found to harbour significantly higher numbers of
      microbial indicators compared to showers/lavatory sources; however, the numbers
      were much lower compared to canteens. Canteen water retention for more than one
      day revealed significantly increased numbers of examined microbial parameters,
      possibly due to secondary contamination or regrowth. Gastrointestinal symptoms
      were not significantly different between the two units despite the significant
      canteen water quality difference. An odds ratio evaluation was conducted on 45
      exposure-illness combinations based on gastrointestinal symptoms, exposure and
      soldiers affiliation. Out of these 45 combinations only 14 resulted in odds ratio
      > 1, where 3 had high values (7.44, 7.46 and 11.2) suggesting a possible
      connection between diarrhoea and/or vomiting versus coliphages and faecal
      coliforms.

PMID- 20154388
TI  - Genes encoding tetracycline resistance in a full-scale municipal wastewater
      treatment plant investigated during one year.
AB  - Tetracycline-resistant bacteria and genes encoding tetracycline resistance are
      common in anthropogenic environments. We studied how wastewater treatment affects
      the prevalence and concentration of two genes, tetA and tetB, that encode
      resistance to tetracycline. Using real-time polymerase chain reaction (PCR) we
      analysed wastewater samples collected monthly for one year at eight key-sites in
      a full-scale municipal wastewater treatment plant (WWTP). We detected tetA and
      tetB at each sampling site and the concentration of both genes, expressed per
      wastewater volume or per total-DNA, decreased over the treatment process. The
      reduction of tetA and tetB was partly the result of the sedimentation process.
      The ratio of tetA and tetB, respectively, to total DNA was lower in or after the
      biological processes. Taken together our data show that tetracycline resistance
      genes occur throughout the WWTP, and that the concentrations are reduced under
      conventional operational strategies.

PMID- 20154389
TI  - Supply system factors associated with microbiological drinking water safety in
      regional New South Wales, Australia, 2001-2007.
AB  - AIM: To determine factors associated with microbiological safety of public
      drinking water systems in regional New South Wales (NSW), Australia. METHOD: We
      analysed 107,000 end-user drinking water samples for an association between
      detection of Escherichia coli and drinking water system features, sample year and
      season using NSW Health Drinking Water Monitoring Program data, 2001-2007. We
      used negative binomial generalized estimating equations with adjustment for
      autocorrelation and clustering. RESULTS: We detected E. coli in over 2% of
      samples from 40% (129/323) of systems. E. coli detection was significantly more
      common in earlier years and during summer (p<0.001). On multivariate analysis E.
      coli detection was significantly associated with smaller systems; watercourse
      sources; no disinfection or disinfection with ultraviolet only; and higher post
      treatment mean turbidity (all p< or =0.01). Detection was most strongly
      associated with lack of disinfection (incidence rate ratio 12.6, p<0.001) and
      smaller supply systems (1% reduction in E. coli detection for each 1,000 person
      increase in supply population, p=0.004). Ultraviolet disinfection alone was the
      least effective disinfection method (p<0.001). CONCLUSION: Even in developed
      countries, drinking water systems without disinfection or serving small
      populations appear vulnerable to the effects of faecal contamination, which
      presents a risk of waterborne disease outbreaks.

PMID- 20154390
TI  - Detection and phylogenetic analysis of hepatitis A virus and norovirus in marine
      recreational waters of Mexico.
AB  - An investigation was conducted to determine hepatitis A virus (HAV) and norovirus
      (NV) presence in marine recreational waters (MRWs) from two Mexican tourists
      beaches (Altata and Mazatlan), located at the northwestern state of Sinaloa,
      Mexico. Also, Binary Logistic Regression (BLR) analyses were conducted between
      physicochemical parameters (temperature, turbidity and salinity) and viral
      organisms (HAV and NV). A total of 32 MRWs samples were collected from April to
      July of 2006. Samples were processed according to the Environmental Protection
      Agency (EPA) adsorption-elution method. Overall, 18 MRWs samples (56.3%) were
      positive for HAV and NV; 4 (22.2%) were obtained from Altata and 14 (77.8%) from
      Mazatlan. HAV was detected in 3 MRWs samples (9.4%) and NV in 15 samples (46.8%).
      Phylogenetic analysis showed the presence of genotype I sub genotype B for HAV
      and NV genogroup II. BLR analysis showed significant correlations between NV and
      physicochemical parameters (temperature, turbidity and salinity) (p=0.017,
      p=0.08, p=0.048, respectively). No significant correlation between
      physicochemical parameters and HAV was observed. The results indicated that MRW
      quality of Sinaloa beaches is affected by human faecal pollution. Viral
      surveillance programs should be implemented to minimize health risks to bathers.

PMID- 20154391
TI  - Diversity and antifungal susceptibility of yeasts isolated by multiple-tube
      fermentation from three freshwater lakes in Brazil.
AB  - The diversity and antifungal resistance of yeasts able to grow at 37 degrees C
      and the occurrence of bacterial indicators of water quality were studied in three
      lakes in Southeastern Brazil. The densities of yeasts, Escherichia coli,
      Enterococcus spp. and Pseudomonas aeruginosa were determined by the multiple-tube
      fermentation technique, and counts of heterotrophic bacteria were determined
      using the pour plate method. The yeasts were identified using physiological and
      molecular techniques and their resistance to amphotericin B, itraconazole and
      fluconazole was tested. Yeast occurrence was significantly correlated only with
      the density of fecal coliforms. Candida krusei, C. guilliermondii and C.
      tropicalis, the most frequently isolated yeast species, are associated with fecal
      contamination of water by warm-blooded animals. Yeast isolates were most
      resistant to amphotericin B (21.7%), followed by itraconazole (20%) and then
      fluconazole (2.8%). In addition to tests for the fecal coliform group, the
      density of yeasts grown at 37 degrees C could be used as a complementary
      microbial indicator that aquatic environments contain organic matter of human
      origin. The incidence of yeast species resistant to three antifungal drugs shows
      that these microorganisms could pose a health risk to the people who use these
      lakes for recreation.

PMID- 20154392
TI  - The degradation of diethyl phthalate (DEP) during ozonation: oxidation by
      products study.
AB  - The degradation of diethyl phthalate (DEP) in an aqueous solution during
      ozonation was investigated by identifying the oxidation intermediates using GC
      MS. The experiments were carried out in semi-batch mode with a 1.5 mg l(-1)-min
      ozone dose. The proposed degradation pathways were divided into hydrolysis of the
      aliphatic chain (pathway (A)) and hydroxylation resulting from OH attack in the
      aromatic ring (pathway (B)). With increasing ozone dose, the aromatic ring of DEP
      was opened and acidic compounds, such as malonic acid, succinic acid and glutaric
      acid were formed. In addition, the ozonation of DEP for 18 min induced hydrogen
      peroxide (H(2)O(2)) generation at levels six times higher than pure water. Of the
      intermediates indentified, phthalic acid (PA) and phthalic anhydride (PAH)
      enhanced the degradation of DEP by promoting ozone decomposition.

PMID- 20154393
TI  - A Cryptosporidium hominis outbreak in north-west Wales associated with low oocyst
      counts in treated drinking water.
AB  - An outbreak in the autumn of 2005 resulted in 218 confirmed cases of
      Cryptosporidium hominis. The attack rate (relative risk 4.1, 95%CI 2.8-9.1) was
      significantly higher in the population supplied by Cwellyn Water Treatment Works
      (WTW). A case-control study demonstrated a statistically significant association
      (odds ratio 6.1, 95% CI 1.8-23.8) between drinking unboiled tap water and C.
      hominis infection. The association remained significant in a logistic regression
      analysis, with an adjusted odds ratio of 1.30 (95 CI 1.05-1.61) per glass of
      unboiled tap water consumed per day. This evidence together with environmental
      and associated microbiological investigations, and the absence of effective
      treatment to remove Cryptosporidium oocysts at the WTW, led to the conclusion
      that the outbreak was waterborne. Oocyst counts in final treated water at the WTW
      and at different points in the distribution system were consistently very low,
      maximum count in continuous monitoring 0.08 oocysts per 10 litres. Data from
      continuous monitoring and the epidemic curve is consistent with the hypothesis
      that low numbers of oocysts of C hominis were present in treated water
      continuously during the outbreak and these were of sufficient infectivity to
      cause illness. All surface water derived water supplies present a potential risk
      to human health and appropriate control measures should be in place to minimise
      these risks.

PMID- 20154394
TI  - Detection of Cryptosporidium species and sources of contamination with
      Cryptosporidium hominis during a waterborne outbreak in north west Wales.
AB  - As part of investigations into the cause of a waterborne outbreak of
      Cryptosporidium hominis infection linked to a mains water supply, surface waters
      and wastewater treatment plants were tested for Cryptosporidium spp. Oocyst
      counts in base flow surface water samples ranged from nil to 29 per 10 l. Oocyst
      counts in effluent from a community wastewater treatment plant were up to 63 fold
      higher and breakout from one septic tank five logs higher. There were no peak
      (storm) flow events during the investigation. C. hominis, four named genotypes
      (cervine, muskrat II, rat, W19) and six new small subunit ribosomal RNA gene
      sequences were identified. Four of the new sequences were closely related to
      Cryptosporidium muskrat genotype I, one was closely related to the fox genotype
      and one to Cryptosporidium canis. C. hominis was found extensively in the
      catchment, but only at sites contaminated by wastewater, and in the treated water
      supply to the affected area. All were gp60 subtype IbA10G2, the outbreak subtype.
      Multiple routes of contamination of the reservoir were identified, resulting in
      persistent detection of low numbers of oocysts in the final water. This work
      demonstrates the utility of genotyping Cryptosporidium isolates in environmental
      samples during outbreak investigations.

PMID- 20154395
TI  - Reducing the impact of summer cattle grazing on water quality in the Sierra
      Nevada Mountains of California: a proposal.
AB  - The Sierra Nevada Mountain range serves as an important source of drinking water
      for the State of California. However, summer cattle grazing on federal lands
      affects the overall water quality yield from this essential watershed as cattle
      manure is washed into the lakes and streams or directly deposited into these
      bodies of water. This organic pollution introduces harmful microorganisms and
      also provides nutrients such as nitrogen and phosphorus which increase algae
      growth causing eutrophication of otherwise naturally oligotrophic mountain lakes
      and streams. Disinfection and filtration of this water by municipal water
      districts after it flows downstream will become increasingly costly. This will be
      compounded by increasing surface water temperatures and the potential for toxins
      release by cyanobacteria blooms. With increasing demands for clean water for a
      state population approaching 40 million, steps need to be implemented to mitigate
      the impact of cattle on the Sierra Nevada watershed. Compared to lower
      elevations, high elevation grazing has the greatest impact on the watershed
      because of fragile unforgiving ecosystems. The societal costs from non-point
      pollution exceed the benefit achieved through grazing of relatively few cattle at
      the higher elevations. We propose limiting summer cattle grazing on public lands
      to lower elevations, with a final goal of allowing summer grazing on public lands
      only below 1,500 m elevation in the Central and Northern Sierra and 2,000 m
      elevation in the Southern Sierra.

PMID- 20154396
TI  - Knowledge of measures to safeguard harvested rainwater quality in rural domestic
      households.
AB  - Given the possibility of waterborne diseases caused by inappropriate rainwater
      harvesting systems, a survey was conducted in Uganda to assess existing knowledge
      of both physical and non-physical measures that safeguard harvested rainwater.
      Households who had received rainwater tanks were assessed on issues related to
      harvested rainwater quality. The study shows that 84% of respondents were aware
      of various sources of rainwater contamination, but only 5% were aware that they
      needed to adjust use of rainwater, depending on whether they cleaned the tank or
      not. Most of the respondents were not aware that gutter cleaning was necessary to
      improve water quality. Indeed, as the water from the collection surface is
      channelled through gutters, a number of measures need to be taken to control the
      entry of contaminations and subsequent growth of pathogens in the tank, e.g.
      first flush diverts, installation of filters, chemical use and mesh cleaning. The
      majority, however, did not take adequate care of the gutters and this impacts on
      health and social livelihood. Overall, the findings emphasize the need to provide
      more information to households when installing water harvesting tanks to ensure
      that the harvested rainwater is of high quality.

PMID- 20154397
TI  - Analysis of the evolution in the circulation of HAV and HEV in eastern Spain by
      testing urban sewage samples.
AB  - The aim of the study was to analyse the evolution of the prevalence of HAV and
      HEV in the population of eastern Spain by analysing the viruses excreted in urban
      sewage. Raw urban sewage samples were collected and analysed during several years
      using RT-PCR techniques and sequencing analysis. Two limiting regions were
      analysed, one of them having implemented HAV vaccination programs. Acute
      symptomatic HEV cases were also examined. Results were compared with those from
      previous studies in the area using identical methodology. The percentage of
      positive HAV samples in urban sewage fell from 57.4% to 3.1% in 5-10 years in the
      two studied areas in Spain. Around 30% of the urban sewage samples were positive
      for HEV in the absence of agricultural sources of contamination. HEV RNA was also
      detected in four clinical cases of acute hepatitis. The dramatic reduction in the
      presence of HAV in raw urban sewage observed in eastern Spain could be most
      likely related to the general improvement in sanitation. However, these
      improvements would not have an equivalent effect on the circulation of HEV and
      this observation could be explained by the presence of animal reservoirs for HEV,
      which act as external sources of infections.

PMID- 20154398
TI  - Assessment of E. coli and Salmonella spp. infection risks associated with
      different fecal sludge disposal practices in Thailand.
AB  - The proper management of fecal sludge (FS), to block the transmission pathways of
      pathogens, is rarely enforced in many parts of the world. Health risks associated
      with different disposal practices of FS in peri-urban settings of a large
      metropolis in Thailand were assessed; Tha Klong sub-district with indiscriminate
      FS dumping, and Klong Luang sub-district which has an FS treatment system. The
      study showed that indiscriminate FS dumping from along the canal banks and
      discharge of market waste were likely the major sources of E. coli and Salmonella
      spp. in contamination of the canal water. The increased microbial pathogen
      concentrations near the FS treatment facility also indicated contamination risks
      from poorly designed treatment facilities. Quantitative microbial risk assessment
      (QMRA) indicated very high water-related infection risk levels compared to the
      actual locally recorded disease occurrences. These results indicated that the
      QMRA model needs to be modified to take account of immunological differences
      between populations in developed countries, where the model was developed, and
      developing countries. In addition, further sensitivity factors are needed to
      reflect different societal behavior patterns, and therefore contact with
      potentially contaminated water, in different sub-populations of many less
      developed communities.

PMID- 20154399
TI  - Estimators of annual probability of infection for quantitative microbial risk
      assessment.
AB  - Four estimators of annual infection probability were compared pertinent to
      Quantitative Microbial Risk Analysis (QMRA). A stochastic model, the Gold
      Standard, was used as the benchmark. It is a product of independent daily
      infection probabilities which in turn are based on daily doses. An alternative
      and commonly-used estimator, here referred to as the Naive, assumes a single
      daily infection probability from a single value of daily dose. The typical use of
      this estimator in stochastic QMRA involves the generation of a distribution of
      annual infection probabilities, but since each of these is based on a single
      realisation of the dose distribution, the resultant annual infection probability
      distribution simply represents a set of inaccurate estimates. While the medians
      of both distributions were within an order of magnitude for our test scenario,
      the 95th percentiles, which are sometimes used in QMRA as conservative estimates
      of risk, differed by around one order of magnitude. The other two estimators
      examined, the Geometric and Arithmetic, were closely related to the Naive and use
      the same equation, and both proved to be poor estimators. Lastly, this paper
      proposes a simple adjustment to the Gold Standard equation accommodating periodic
      infection probabilities when the daily infection probabilities are unknown.

PMID- 20154400
TI  - The occurrence and sources of Campylobacter spp., Salmonella enterica and
      Escherichia coli O157:H7 in the Salmon River, British Columbia, Canada.
AB  - In this study, we wished to assess the prevalence and determine the sources of
      three zoonotic bacterial pathogens (Salmonella, Campylobacter, and Escherichia
      coli O157:H7) in the Salmon River watershed in southwestern British Columbia.
      Surface water, sewage, and animal faecal samples were collected from the
      watershed. Selective bacterial culture and PCR techniques were used to isolate
      these three pathogens and indicator bacteria from these samples and characterize
      them. Campylobacter was the most prevalent pathogen in all samples, followed by
      Salmonella, and E. coli O157:H7. E. coli O157:H7 and Salmonella isolation rates
      from water, as well as faecal coliform densities correlated positively with
      precipitation, while Campylobacter isolation rates correlated negatively with
      precipitation. Analysis of DNA extracted from water samples for the presence of
      Bacteroides host-species markers, and comparisons of C. jejuni flaA-RFLP types
      and Salmonella serovars from faecal and water samples provided evidence that
      human sewage and specific domestic and wild animal species were sources of these
      pathogens; however, in most cases the source could not be determined or more than
      one source was possible. The frequent isolation of these zoonotic pathogens in
      the Salmon River highlights the risks to human health associated with intentional
      and unintentional consumption of untreated surface waters.

PMID- 20154401
TI  - An international review of the challenges associated with securing 'buy-in' for
      water safety plans within providers of drinking water supplies.
AB  - Since publication of the 3rd Edition of the World Health Organisation (WHO)
      Drinking Water Quality guidelines, global adoption of water safety plans (WSPs)
      has been gathering momentum. Most guidance lists managerial commitment and 'buy
      in' as critical to the success of WSP implementation; yet the detail on how to
      generate it is lacking. This commentary discusses aspects of managerial
      commitment to WSPs. We argue that the public health motivator should be clearer
      and a paramount objective and not lost among other, albeit legitimate, drivers
      such as political or regulatory pressures and financial efficiency.

PMID- 20154402
TI  - Detection of Giardia and Cryptosporidium cysts/oocysts in watersheds and drinking
      water sources in Brazil urban areas.
AB  - The protozoan parasites Giardia and Cryptosporidium have been described as
      important waterborne disease pathogens, and are associated with severe
      gastrointestinal illnesses. The objective of this paper was to investigate the
      presence of Giardia cysts and Cryptosporidium oocysts in samples from watershed
      catchments and treated water sources. A total of 25 water samples were collected
      and examined according to the US EPA--Method 1623, 2005, consisting of 12 from
      drinking water and 13 from raw water. Positive samples from raw water for Giardia
      cysts and Cryptosporidium oocysts were 46.1 and 7.6%, respectively. In finished
      water, positive samples were 41.7% for Giardia cysts and 25.0% for
      Cryptosporidium oocysts. Concentrations of Giardia cysts found in raw water
      samples ranged from "not detected" to 3.4 cysts/L, whereas concentrations of
      Cryptoporidium oocysts ranged from "not detected" to 0.1 oocysts/L. In finished
      water, Giardia concentrations ranged from "not detected" to 0.06 cysts/L, and
      Cryptosporidium, from "not detected" to 0.01 oocysts/L. Concentrations of Giardia
      cysts and Cryptosporidium oocysts were not high in the samples analyzed.
      Nevertheless, the results of this study highlight the need to monitor these
      organisms in both raw and drinking water.

PMID- 20154403
TI  - Waon therapy for cardiovascular disease: innovative therapy for the 21st century.
AB  - Waon therapy is a form of thermal treatment in a dry sauna maintained at a
      temperature of 60 degrees C, which differs from the traditional sauna. Waon
      therapy reportedly improves the hemodynamics, cardiac function, ventricular
      arrhythmias, vascular endothelial function, neurohormonal factors, sympathetic
      nervous system function, and symptoms in patients with chronic heart failure
      (CHF). It has also been demonstrated that the molecular mechanism by which Waon
      therapy improves vascular flow and endothelial function involves increased
      expression of endothelial nitric oxide synthase (eNOS). Furthermore, in a mouse
      model of hindlimb ischemia, repeated Waon therapy increased eNOS protein
      expression, blood flow, and capillary density. Moreover, Waon therapy did not
      increase blood flow and capillary density in eNOS-deficient mice, indicating that
      eNOS is a critical regulator of the angiogenesis induced by this therapy.
      Moreover, repeated Waon therapy is effective for patients with severe peripheral
      arterial disease (PAD), as evidenced by substantial decrease in pain scores,
      increases in both ankle-brachial pressure index and blood flow assessed by laser
      Doppler perfusion imaging, and by formation of new collateral vessels on
      angiography. In addition, ischemic ulcers heal or improve markedly. In
      conclusion, Waon therapy is an innovative and highly promising strategy for
      treating CHF and PAD.

PMID- 20154404
TI  - Combination therapy with olmesartan and azelnidipine improves EDHF-mediated
      responses in diabetic apolipoprotein E-deficient mice.
AB  - BACKGROUND: The endothelium modulates vascular tone by synthesizing and releasing
      several vasodilating factors, including vasodilator prostaglandins, nitric oxide
      (NO) and endothelium-derived hyperpolarizing factor (EDHF). In the present study,
      we examined whether an angiotensin-receptor blocker, a calcium-channel blocker or
      their combination improved EDHF-mediated responses in diabetic apolipoprotein E
      deficient (ApoE(-/-)) mice. METHODS AND RESULTS: We used male C57BL/6N (control)
      and streptozocin-induced diabetic ApoE(-/-) mice. The diabetic ApoE(-/-) mice
      were administered oral vehicle (untreated), olmesartan (OLM, 30 mgxkg(-1)xday(
      1)), azelnidipine (AZL, 10 mgxkg(-1)xday(-1)), their combination (OLM + AZL), or
      hydralazine (HYD 5 mgxkg(-1)xday(-1)) for 5 weeks. In the untreated group,
      systolic blood pressure was significantly higher and both EDHF-mediated
      relaxation and endothelium-dependent hyperpolarization were markedly reduced as
      compared with the control group. Although EDHF-mediated relaxation was not
      significantly improved in the HYD, OLM and AZL groups, it was significantly
      improved in the OLM + AZL group, as was also the case with phosphorylation of Akt
      and endothelial NO synthase (eNOS). In contrast, the endothelium-independent
      relaxation response to sodium nitroprusside or NS-1619 (a direct opener of K(Ca)
      channels) was unaltered in any group. CONCLUSIONS: OLM + AZL may improve the
      severely impaired EDHF-mediated responses in diabetic ApoE(-/-) mice, in which
      activation of the endothelial Akt - eNOS pathway may be involved.

PMID- 20154405
TI  - A randomized controlled open comparative trial of varenicline vs nicotine patch
      in adult smokers: efficacy, safety and withdrawal symptoms (the VN-SEESAW study).
AB  - BACKGROUND: It has been suggested that anti-smoking therapy gives encouraging
      results, but this has not been verified by well-randomized study protocols. The
      present study was a randomized controlled trial of varenicline vs nicotine patch
      in adult smokers for comparison of efficacy, safety and withdrawal symptoms.
      METHODS AND RESULTS: The 32 adult smokers were randomly divided into a
      varenicline group (VG, n=16) and a nicotine patch group (NG, n=16). The primary
      endpoints were the 12- and 24-week smoking-abstinence rates, safety and
      withdrawal symptoms including stress. No significant difference in abstinence
      rates was observed between the 2 groups over weeks 9-12 (71.4% vs 78.6% in the VG
      and NG, respectively), and weeks 9-24 (64.3% vs 71.4%, respectively). The
      frequencies of inability to concentrate at 2, 4, and 8 weeks, and wakeful nights
      at 2 weeks were higher in the VG than in the NG. Adverse side-effects associated
      with a gastrointestinal disorder occurred in 14 cases and 1 case in the VG and
      NG, respectively, and skin allergy was seen in 0 and 9 cases, respectively.
      CONCLUSIONS: The selection of treatment depends on the balance of desired
      acuteness of cessation of smoking and side-effects, such as psychiatric and
      gastrointestinal problems or skin allergy.

PMID- 20154406
TI  - A 3-year clinical outcome after percutaneous coronary intervention using
      sirolimus-eluting stent and off-pump coronary artery bypass grafting for the
      treatment of diabetic patients with multivessel disease.
AB  - BACKGROUND: There are few data to compare the long-term efficacy of sirolimus
      eluting stent (SES) and off-pump coronary artery bypass grafting (OPCAB) for
      diabetic patients with multivessel disease (MVD). METHODS AND RESULTS: In a
      single-center non-randomized registry, 208 diabetic patients with MVD were
      examined (SES group: n=92, OPCAB group: n=116). The occurrence of major adverse
      cardiac and cerebrovascular events (MACCE, defined as all-cause death, non-fatal
      myocardial infarction, cerebrovascular event, and repeat revascularization) was
      compared between the 2 groups. Fasting blood glucose level, type of diabetic
      treatment and the prevalence of diabetic major vascular complications were
      similar between groups. The SES group had a significantly higher prevalence of 2
      vessel disease and a significantly lower prevalence of 3-vessel disease compared
      with the OPCAB group. During the follow-up period (mean: 42+/-8 months), the rate
      of revascularization was significantly higher in the SES group than the OPCAB
      group (21% vs 6.9%, P=0.003). On the other hand, there was a significant higher
      occurrence of cerebrovascular events in the OPCAB group. Finally, the cumulative
      MACCE was similar between the 2 groups (27% vs 23%, P=0.492). CONCLUSIONS: At the
      3-year clinical follow-up, the prevalence of MACCE in diabetic patients with MVD
      was comparable between the SES and the OPCAB groups.

PMID- 20154407
TI  - Prospective electrocardiogram-gated axial 64-detector computed tomographic
      angiography vs retrospective gated helical technique to assess coronary artery
      bypass graft anastomosis: comparison of image quality and patient radiation dose.
AB  - BACKGROUND: In the present study the effective dose and image quality at distal
      anastomoses were retrospectively compared between prospective electrocardiogram
      (ECG)-gated axial and retrospective ECG-gated helical techniques on 64-detector
      computed tomographic (CT) angiography following coronary artery bypass graft
      surgery. METHODS AND RESULTS: Following bypass surgery, 52 patients with a heart
      rate <65 beats/min underwent CT angiography: 26 patients each with prospective
      and retrospective ECG gating techniques. The effective dose was compared between
      the 2 groups using a 4-point scale (4, excellent; 1, poor) to grade the quality
      of curved multiplanar reformation images at distal anastomoses. Patient
      characteristics of the 2 groups were well matched, and the same CT scan
      parameters were used for both, except for the interval between surgery and CT
      examination, tube current, and image noise index. Image quality scores did not
      differ significantly (3.26+/-0.95 vs 3.35+/-0.87; P=0.63), but the effective dose
      was significantly lower in the prospective (7.3+/-1.8 mSv) than in the
      retrospective gating group (23.6+/-4.5 mSv) (P<0.0001). CONCLUSIONS: Following
      bypass surgery, 64-detector CT angiography using prospective ECG gating is
      superior to retrospective gating in limiting the radiation dose and maintaining
      the image quality of distal anastomoses.

PMID- 20154408
TI  - Fasudil hydrochloride induces osteoblastic differentiation of stromal cell lines,
      C3H10T1/2 and ST2, via bone morphogenetic protein-2 expression.
AB  - Rho-kinase (ROK), downstream of the mevalonate pathway, is detrimental to
      vessels, and suppressing its activity is a target for the treatment of human
      disease such as coronary artery disease and pulmonary hypertension. Recent
      studies have shown that ROK has a crucial role in bone metabolism. However, the
      role of ROK in stromal cells is still unclear. The present study was undertaken
      to investigate the effect of a ROK inhibitor, fasudil hydrochloride, on stromal
      cell lines, C3H10T1/2 and ST2. In both cells, Fasudil significantly stimulated
      alkaline phosphatase activity and enhanced cell mineralization. Moreover, fasudil
      significantly increased the mRNA expression of collagen-I, osteocalcin, and bone
      morphogenetic protein-2 (BMP-2). Supplementation of noggin, a BMP-2 antagonist,
      significantly reversed the fasudil-induced collagen-I and osteocalcin mRNA
      expression in both cells. These findings suggest that fasudil induces the
      osteoblastic differentiation of stromal cells via enhancing BMP-2 expression, and
      that this drug might be beneficial for not only atherosclerosis but also
      osteoporosis by promoting bone formation.

PMID- 20154409
TI  - [Current state and perspectives of pharmacological and non-pharmacological
      treatment of atrial fibrillation: overview].

PMID- 20154410
TI  - [Best strategy for the treatment of atrial fibrillation: reconsideration after
      randomized multicenter clinical trials in Japan].

PMID- 20154411
TI  - [Upstream approach for atrial fibrillation].

PMID- 20154412
TI  - [Downstream approaches to atrial fibrillation: the new rhythm control drugs and
      promising targets].

PMID- 20154413
TI  - [Non-pharmacological therapy for atrial fibrillation: catheter ablation based on
      extensive pulmonary vein isolation].

PMID- 20154414
TI  - [Third-party accreditation (external evaluation) for self-management of animal
      experiments].

PMID- 20154415
TI  - [Transporters involved in hepatobiliary transport of drugs].

PMID- 20154416
TI  - [Applications of PET imaging in the preclinical stage of drug development].

PMID- 20154417
TI  - [Prediction of the pharmacokinetics of clinical candidates in humans from in
      vitro data].

PMID- 20154418
TI  - Cloning and characterization of the rhesus monkey nociceptin/orphanin FQ
      receptor.
AB  - We succeeded in cloning the rhesus monkey nociceptin/orphanin FQ peptide (NOP)
      receptor. The nucleotide sequence and amino acid sequence of the rhesus monkey
      NOP receptor were 95.9% and 97.8%, respectively, identical to the human NOP
      receptor. There was no significant difference between the rhesus monkey NOP
      receptor and the human NOP receptor in the binding affinity of [(125)I]
      [Thy(14)]nociceptin and the binding of [(35)S]guanosine 5'-O-(gamma
      thio)triphospate ([(35)S]GTPgammaS) stimulated by nociceptin/orphanin FQ (N/OFQ).
      A selective NOP receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl-3
      hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one ((+)-J
      113397) inhibited the [(35)S]GTPgammaS binding activated by N/OFQ using the
      membrane of the rhesus monkey NOP receptor. The antagonistic activity of (+)-J
      113397 to the rhesus monkey NOP receptor was comparable to that to the human NOP
      receptor. Thus, N/OFQ acts via activation of the NOP receptor in both human and
      rhesus monkeys without significant species differences.

PMID- 20154419
TI  - An insertion of intracisternal A-particle retrotransposon in a novel member of
      the phosphoglycerate mutase family in the lew allele of mutant mice.
AB  - Intracisternal A-particle retrotransposons (IAPs) are known, moveable, retrovirus
      like elements and are defective in envelope protein synthesis in the mouse
      genome. Insertion of IAP elements can either interupt or enhance gene function or
      expression. Using a mouse model called lethal wasting (lew), we recently
      identified the insertion of an IAP sequence in a gene, 9630033F20Rik, that
      contains domains involved in glycolysis. The expression pattern of the
      9630033F20Rik gene between various normal and diseased tissues was determined by
      semi-quantitative RT-PCR. The effect of the insertion mutation in 9630033F20Rik
      on glycolysis in heart, muscle, and brain tissues was further investigated using
      oligonuleotide microarray analysis. Results indicated that the expression of
      9630033F20Rik is ubiquitous and its signal is relatively higher in heart and
      brain tissues. The insertion caused the deletion of exon 5 and decreased
      expression of this gene in all the tissues studied in the lew mice. Changes in
      the expression levels of glycolytic genes mainly occured in muscle tissue,
      raising a possibility that 9630033F20Rik may function as one of the
      transcriptional regulators of glycolytic genes in skeletal muscle. However,
      considering the fact that a single nucleotide mutation in vesicle-associated
      membrane protein 1 (VAMP1) has been reported as the causal gene for the lew
      mouse, how much of an impact the IAP insertion in the lew mouse phenotype has on
      glycolytic genes compared to the effect from the VAMP1 mutation responsible for
      the lew mouse phenotype should be further investigated.

PMID- 20154420
TI  - Molecular cloning, characterization and tissue distribution of six splice
      variants of activin type IIA receptor (ActRIIA) from grass carp (Ctenopharyngodon
      idellus).
AB  - Activin type II receptor (ActRII) is crucial for the assembly of the
      ligand/receptor complex and the activation of downstream cascades in activin
      signaling pathway. In this study, we identified six variants of grass carp
      ActRIIA which can be generated through three alternative splicing events (defined
      as AS1, AS2 and AS3). AS1 induces a spliced segment encoding 14 amino acids
      located in the external juxtamembrane region of the receptor. However, both AS2
      and AS3 occur at the same cleavage site of kinase domain and induce a premature
      termination codon. Indeed, AS2 inserts a fragment of 79 bp while AS3 generates a
      new 3' terminal of cDNA with poly(A) signals. The full length cDNA of the
      shortest variant was shown to be 2001 bp encoding 514 amino acids with sequence
      identity of 79-95% to counterparts in other species. Homology modeling studies
      showed grass carp ActRIIA exhibits a characteristic three-finger toxin fold in
      the extracellular domain and a conserved bilobal architecture in the
      intracellular kinase domain. Semi-quantitative RT-PCR analysis revealed that six
      variants showed different expression patterns in selected tissues of grass carp.
      This study will be helpful for a better understanding of the physiological role
      of activin signaling in lower vertebrates.

PMID- 20154421
TI  - Distribution of complete and defective copies of the Tol1 transposable element in
      natural populations of the medaka fish Oryzias latipes.
AB  - DNA-based transposable elements are present in the genomes of various organisms,
      and generally occur in autonomous and nonautonomous forms, with a good
      correspondence to complete and defective copies, respectively. In vertebrates,
      however, the vast majority of DNA-based elements occur only in the nonautonomous
      form. Until now, the only clear exception known has been the Tol2 element of the
      medaka fish, which still causes mutations in genes of the host species. Here, we
      report another exception: the Tol1 element of the same species. This element was
      thought likely to be a "dead" element like the vast majority of vertebrate
      elements, but recent identification of an autonomous Tol1 copy in a laboratory
      medaka strain gave rise to the possibility that the element is still "alive" in
      medaka natural populations. We examined variation in the structure of Tol1 copies
      through genomic Southern blot analysis, and revealed that 10 of the 32 fish
      samples examined contained full-length Tol1 copies in their genomes. The
      frequency at which these copies occur among Tol1 copies is at most 0.5%, yet some
      of them still have the ability to produce a functional transposase. The medaka
      fish thus harbors two active DNA-based elements in its genome, and is in this
      respect unique among vertebrates.

PMID- 20154422
TI  - Transgenic Drosophila simulans strains prove the identity of the speciation gene
      Lethal hybrid rescue.
AB  - Speciation genes are responsible for genetic incompatibilities in hybrids of
      incipient species and therefore participate in reproductive isolation leading to
      complete speciation. Hybrid males between Drosophila melanogaster females and D.
      simulans males die at late larval or prepupal stages due to a failure in
      chromosome condensation during mitosis. However a mutant male of D. simulans,
      named Lethal hybrid rescue (Lhr), produces viable hybrid males when crossed to
      females of D. melanogaster. Recently the Lhr gene has been proposed as
      corresponding to the CG18468 gene in D. melanogaster. However this identification
      relied on sequence characteristics more than on a precise mapping and the use of
      the GAL4/UAS system to drive the transgene in D. melanogaster might have
      increased the complexity of interaction. Thus here we propose an independent
      identification of the Lhr gene based on a more precise mapping and transgenic
      experiments in D. simulans. We have mapped the Lhr gene by using Single
      Nucleotide Polymorphisms (SNPs) and identified within the candidate region the
      gene homologous to CG18468 as the Lhr gene as it was previously reported.
      Transgenic experiments in D. simulans with the native promoter of CG18468 prove
      that it is the Lhr gene of D. simulans by inducing the lethality of the hybrid
      males.

PMID- 20154423
TI  - Molecular characterization of mutations induced by gamma irradiation in rice.
AB  - In order to analyze mutations induced by gamma irradiation in higher plants, we
      irradiated rice with gamma rays and screened for mutations expressing phenotypes
      of glutinous endosperm (wx), chlorophyll b deficiency, endosperm protein
      deficiency, gibberellin-related dwarfism, and shortened plastochron-in order to
      clarify types of mutations. Nucleotide sequence analysis showed that the most
      frequent mutation induced by gamma rays was deletion, particularly small
      deletion. Of the 24 mutations, 15 were small deletions (1-16 bp), four were large
      deletions (9.4-129.7 kbp), three were single-base substitutions, and two were
      inversions. Deletions 100 bp-8 kbp in length were not found, suggesting that
      gamma irradiation is unlikely to induce deletions of 100 bp to 8 kbp but is more
      likely to induce deletions between 1 and several ten bp or those of around 10 kbp
      or more. Based on the results, reverse genetics applications may be possible for
      gamma irradiation-induced deletions in rice by mismatch cleavage analysis used in
      Targeting Induced Local Lesions IN Genomes (TILLING) to detect small deletions
      and base substitutions or by using array comparative genomic hybridization (aCGH)
      to detect large deletions.

PMID- 20154424
TI  - Comparative differentiation in mitochondrial and chloroplast DNA among cultivated
      potatoes and closely related wild species.
AB  - A total of 476 accessions of seven cultivated and 32 wild potato species
      previously characterized by nuclear DNA (nDNA) and chloroplast DNA (ctDNA) marker
      analyses were employed to the mitochondrial DNA (mtDNA) marker analysis. Fourteen
      simple sequence repeat (SSR) markers with mononucleotide repeat regions were
      developed from the potato mtDNA, although their variability was extremely low.
      Six mtDNA markers including three developed SSR markers disclosed 40 banding
      patterns that discriminated 63 different mtDNAs. For the same set of samples, 72
      ctDNA banding patterns discriminated 129 different ctDNAs. Consequently, 164
      haplotypes were distinguished. The correlation between ctDNA and mtDNA
      differentiation was positive (r = 0.226), but poor when compared with that
      between ctDNA and nDNA (r = 0.415), which likely lowered the utility of mtDNA
      polymorphisms in evaluating relationships among these species. Nevertheless, a
      finding of a unique mtDNA type in all T-type ctDNA holders (S. tuberosum and S.
      tarijense) strongly supports S. tarijense functioned as a maternal ancestor of
      potato.

PMID- 20154425
TI  - Photoperiod-dependent regulation of cell growth by PpCCA1a and PpCCA1b genes
      encoding single-myb clock proteins in the moss Physcomitrella patens.
AB  - The PpCCA1a and PpCCA1b genes of the moss Physcomitrella patens are functional
      homologs of the Arabidopsis thaliana circadian clock genes CCA1/LHY. We made use
      of disruptant lines for PpCCA1a and/or PpCCA1b to elucidate the physiological
      significance of these genes in the growth of moss protonemal tissue under
      alternating day/night cycles. Protonemal cells of the double disruptant line,
      carrying neither of the two genes, grew faster than those of the wild-type plant
      (WT) in long days (LD), whereas no difference in the growth rate was detected
      between them in short days (SD). The double disruptant line also showed day
      length-dependent phenotypic changes in the PpCCA1b promoter activity: the diurnal
      profile of bioluminescence from the P(CCA1b)::LUC+ reporter strain was more
      significantly affected in LD than in SD. These observations are the first
      demonstration of a physiological function of the circadian clock in non
      angiosperm land plants, and are consistent with recent findings that the clock
      controls hypocotyl elongation of A. thaliana in a photoperiod-dependent manner.

PMID- 20154426
TI  - MODA: an efficient algorithm for network motif discovery in biological networks.
AB  - In recent years, interest has been growing in the study of complex networks.
      Since Erdos and Renyi (1960) proposed their random graph model about 50 years
      ago, many researchers have investigated and shaped this field. Many indicators
      have been proposed to assess the global features of networks. Recently, an active
      research area has developed in studying local features named motifs as the
      building blocks of networks. Unfortunately, network motif discovery is a
      computationally hard problem and finding rather large motifs (larger than 8
      nodes) by means of current algorithms is impractical as it demands too much
      computational effort. In this paper, we present a new algorithm (MODA) that
      incorporates techniques such as a pattern growth approach for extracting larger
      motifs efficiently. We have tested our algorithm and found it able to identify
      larger motifs with more than 8 nodes more efficiently than most of the current
      state-of-the-art motif discovery algorithms. While most of the algorithms rely on
      induced subgraphs as motifs of the networks, MODA is able to extract both induced
      and non-induced subgraphs simultaneously. The MODA source code is freely
      available at: http://LBB.ut.ac.ir/Download/LBBsoft/MODA/

PMID- 20154427
TI  - Global dissemination of endoscopic submucosal dissection for early gastric
      cancer.

PMID- 20154428
TI  - A comparison of outcomes of endoscopic submucosal dissection (ESD) For early
      gastric neoplasms between high-volume and low-volume centers: multi-center
      retrospective questionnaire study conducted by the Nagano ESD Study Group.
AB  - OBJECTIVE: Outcomes of endoscopic submucosal dissection (ESD) for early gastric
      neoplasms at low-volume centers have been unknown, because all previous reports
      have studied in advanced single centers. The aim of this study was to compare ESD
      outcomes between high- and low-volume centers. METHODS: A retrospective
      questionnaire survey was conducted and 30 centers (96.8%) responded. The complete
      en-bloc resection rate (CERR) and the incidence of complications were analyzed.
      Early gastric cancer (EGC) was divided into three categories on the basis of
      pathological diagnosis-standard indication (SI), expanded indication (EI) and out
      of-indication (OI). RESULTS: A total of 703 early gastric neoplasms (586 EGCs,
      117 gastric adenomas) were treated with ESD from January to December 2005. The
      institutions that treated more than 30 cases a year were classified as high
      volume centers, and those with less than 30 cases, low-volume centers. In SI, the
      CERRs at high- and low-volume centers were 92.1% and 91.1%, in EI, CERRs were
      86.2% and 82.6% and in OI, CERRs were 80.3% and 88.0%. The perforation rates at
      high- and low-volume centers were 3.6% and 4.7%. The intra-operative bleeding
      rates at high- and low-volume centers were 0.26% and 0%, while the delayed
      bleeding rates were 0% and 0.63%. CONCLUSION: There were no significant
      difference in the outcomes of ESD for early gastric neoplasms between high- and
      low volume centers.

PMID- 20154429
TI  - Changes in metabolic syndrome and its components with lifestyle modification in
      Japanese men.
AB  - OBJECTIVE: Changes in metabolic syndrome and its components with lifestyle
      modification were evaluated in Japanese men. METHODS: We used data for 160
      Japanese men (45.6+/-8.8 years) with a 1-year follow up. Anthropometric, blood
      examination and blood pressure measurements were evaluated. Metabolic syndrome
      was defined by using a criterion in Japan. All subjects were given instructions
      by well-trained medical staff on how to change their lifestyle. RESULTS: With a 1
      year follow-up, anthropometric parameters, blood pressure (BP), triglyceride and
      HDL cholesterol were significantly improved and the prevalence of metabolic
      syndrome was significantly reduced. The number of subjects with abdominal obesity
      at baseline and at follow-up was higher (81 men) than that of subjects with other
      components at baseline and at follow-up. Parameters at baseline were
      significantly correlated with changes in parameters for one year. With lifestyle
      modification, the level of 163 mmHg in systolic BP (SBP), 115 mmHg in diastolic
      BP (DBP), 226 mg/dL in triglyceride and 33 mg/dL in HDL cholesterol at baseline
      was estimated to improve to the level without medications with a 1-year follow
      up. CONCLUSION: Lifestyle modification is useful for improving metabolic syndrome
      and its components. However, items of metabolic syndrome were improved, even when
      the abdominal circumference was greater than the normal value for Japanese men.

PMID- 20154430
TI  - Elevation of serum immunoglobulin G in Hashimoto's thyroiditis and decrease after
      treatment with L-thyroxine in hypothyroid patients.
AB  - OBJECTIVE: We undertook an investigation on the frequency and magnitude of
      elevated serum immunoglobulin G (IgG), and effects of treatment with L-thyroxine
      (T(4)) in patients with Hashimoto's thyroiditis. METHODS: Ninety-seven
      consecutive cases of Hashimoto's thyroiditis, 104 patients with simple goiter,
      and 75 normal subjects were analyzed retrospectively. Serum total T(4), thyroid
      stimulating hormone (TSH), microsomal hemagglutination antibody (MHA) titer, and
      IgG were determined in all subjects. RESULTS: IgG was significantly elevated in
      patients with Hashimoto's thyroiditis as a group, and elevation above the upper
      limit of the normal range was found mostly in patients with hypothyroidism. There
      is a significant negative correlation between serum total T(4) and IgG, and a
      significant positive correlation between TSH and IgG in patients with Hashimoto's
      thyroiditis. In addition, MHA titer was positively correlated with serum IgG. In
      a longitudinal analysis of hypothyroid patients with Hashimoto's thyroiditis,
      restoration of euthyroidism by L-T(4) administration was associated with a
      consistent decrease in serum IgG. CONCLUSION: Serum IgG concentration is
      increased in patients with Hashimoto's thyroiditis, particularly in hypothyroid
      patients, and treatment with L-T(4) in such patients lowers IgG levels.

PMID- 20154431
TI  - Comparison of clinical and radiological features of pneumocystis pneumonia
      between malignancy cases and acquired immunodeficiency syndrome cases: a
      multicenter study.
AB  - BACKGROUND: The clinical features of pneumocystis pneumonia (PCP) differ
      according to the predisposing factors responsible for immunosuppression. Although
      PCP in patients with acquired immunodeficiency syndrome (AIDS) has been
      extensively described, its characteristics in non-AIDS patients, such as those
      with malignancies, are not thoroughly documented. STUDY OBJECTIVE: To
      characterize and compare the clinical and imaging features of PCP in patients
      with malignancies with those in AIDS patients. DESIGN: A multi-center
      retrospective study. PATIENTS AND MEASUREMENTS: We evaluated the clinical and
      radiological features of PCP in 21 patients with malignancies and in 17 with
      AIDS. Clinical presentation, serum markers, oxygenation, CT findings, and outcome
      were examined. RESULTS: The patients with malignancies showed shorter durations
      of symptoms before PCP was diagnosed. The levels of serum markers and the
      oxygenation index did not differ. CT showed diffuse or widespread ground-glass
      opacity (GGO) in all of the patients evaluated. None of the AIDS patients
      demonstrated consolidation, whereas half of the patients with malignancy showed
      consolidation along with GGO. The extent of GGO scored on CT images was
      significantly greater in the AIDS patients. No correlation was observed between
      the CT findings and other clinical parameters. All of the AIDS patients recovered
      from PCP, whereas six patients with malignancies died within a month after the
      onset of PCP. CONCLUSION: The characteristics of the CT images differed between
      the patient groups with different underlying disorders, although it remains to be
      determined whether CT findings are associated with other clinical features or are
      predictive of the outcome of PCP.

PMID- 20154432
TI  - Reversible alcohol-related dementia: a five-year follow-up study using FDG-PET
      and neuropsychological tests.
AB  - OBJECTIVE: As the pathophysiology of alcohol-related dementia (ARD) is unclear,
      we examined a patient with reversible ARD using neuropsychological tests and
      (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: 
      DESIGN: A five-year follow-up case study with neuropsychological tests and FDG
      PET. SETTING: Kyoto University Hospital. Patients A 42-year-old patient who was
      unable to perform his office duties because of slowly progressive amnesia with
      executive dysfunction. RESULTS: The initial evaluation with neuropsychological
      tests showed severe verbal memory disturbance. The patient did not discuss his
      excessive alcohol consumption in the initial history-taking session and thiamine
      deficiency was absent; therefore, early-stage Alzheimer's disease was suspected.
      Later, the patient revealed prior excessive alcohol intake and his cognitive
      function improved markedly after a period of abstinence. Retrospective analysis
      of initial FDG-PET images using a voxel-wise statistical method revealed glucose
      hypometabolism in the diencephalon and basal forebrain. Follow-up for 5 years
      after the initial evaluation showed improved cognitive function and recovery of
      glucose metabolism in the two brain regions. CONCLUSION: Hypofunction in the
      diencephalon and basal forebrain was associated with cognitive decline in our
      patient. This case may provide evidence for the etiopathic brain regions in
      reversible type ARD.

PMID- 20154433
TI  - Evaluation of the risk of intercostal artery laceration during thoracentesis in
      elderly patients by using 3D-CT angiography.
AB  - OBJECTIVE: Our study was undertaken to determine the location of the tortuous
      intercostal artery in elderly patients by using 3D-CT angiography in order to
      prevent laceration during thoracentesis. METHODS: We evaluated the data of 3D-CT
      angiography of the intercostal artery in consecutive patients who had undergone
      contrast chest CT scan in our hospital from December 2007 to April 2008. We
      considered the "percent safe space" (the shortest lower rib-to-intercostal artery
      distance/the upper rib-to-lower rib distance) to be an index of safety that can
      be used to prevent laceration of the intercostal artery during thoracentesis. We
      measured this index at 3 points: the total site (5-10 cm lateral to the spine),
      the lateral site (9-10 cm lateral to the spine), and the medial site (5-6 cm
      lateral to the spine). RESULTS: We evaluated 33 cases (25 males and 8 females;
      mean age, 74.2 years). The mean percent safe space at the total site was 58.6%.
      The percent safe space at the total site tended to decrease with advancing age,
      but the correlation was low (p=0.0378, r=-0.3631). The percent safe space at the
      lateral site (mean, 79.8%) was significantly higher than that at the medial site
      (61.2%, p<0.0001). CONCLUSION: We showed that the intercostal artery is tortuous
      and does not always lie along the inferior edge of the rib and that the percent
      safe space at the lateral site is significantly higher than that at the medial
      site in elderly patients.

PMID- 20154434
TI  - Clinical course of tuberculous peritonitis determined by laparoscopy.
AB  - We describe laparoscopic findings of tuberculous peritonitis in a 68-year-old man
      and those at follow-up 8 months later. The initial laparoscopic findings revealed
      typical yellowish-white nodules on the liver surface, and histological findings
      showed granulomas with caseous necrosis. Laparoscopy 8 months later showed that
      anti-tubercular drugs had diminished the nodules and adhesions with a fibrin net
      appearance were evident. Laparoscopy and biopsy are useful for a rapid diagnosis
      of tuberculous peritonitis.

PMID- 20154435
TI  - Relationship of high-molecular-weight adiponectin levels to visceral fat
      accumulation in hemodialysis patients.
AB  - OBJECTIVE: High molecular weight adiponectin (HMW ADPN) plays an important role
      in the regulation of insulin resistance and atherogenic processes. However, the
      role of HMW ADPN remains to be determined in hemodialysis (HD) patients. PATIENTS
      AND METHODS: We measured serum HMW ADPN in 49 HD patients (age: 62.4+/-12.0
      years, time on HD: 8.4+/-6.4 years, male/female=30/19), and examined the
      association between HMW ADPN and visceral fat area (VFA) estimated by abdominal
      CT scans. RESULTS: Serum HMW ADPN concentrations were weakly and inversely
      correlated with serum TG (r=-0.271, p=0.0598), but significantly and positively
      correlated with HDL cholesterol (r=0.392, p=0.0050). Serum HMW ADPN levels were
      positively correlated with BMI (r=0.472, p=0.0084) in male patients, and the HMW
      ADPN levels were positively correlated with serum levels of HDL cholesterol
      (r=0.514, p=0.0243) and TG (r=0.605, p=0.0061).The regression coefficient between
      VFA and HMW ADPN was -0.491 (p<0.003). Multiple stepwise regression analyses
      showed that VFA was the most significant and independent determinant of serum HMW
      ADPN concentration. CONCLUSION: These findings suggest that HMW ADPN may be
      inversely associated with visceral fat accumulation in HD patients.

PMID- 20154436
TI  - Hyperpotassemia and bradycardia in a bedridden elderly woman with selective
      hypoaldosteronism associated with low renin activity.
AB  - A bedridden 85-year-old woman had hyperpotassemia (7.7 mEq/L) and bradycardia
      (30/min). Endocrinologic findings revealed a decrease in the renin-aldosterone
      system and normal adrenoglucocorticoid function. The results were consistent with
      the abnormalities seen in selective hypoaldosteronism with low renin activity. In
      addition, 9 of 11 patients, selected randomly from 72 bedridden elderly patients
      with normal serum sodium and potassium levels in our hospital, had diminished
      plasma renin activity (PRA) and plasma aldosterone concentration (PAC). The
      present patient was prescribed nonsteroidal anti-inflammatory drug (NSAID). NSAID
      reduces renal potassium excretion through the inhibition of renal prostaglandin
      synthesis. Therefore, the use of NSAID in bedridden elderly patients might
      intensify the underlying asymptomatic hypoaldosteronism and cause life
      threatening hyperpotassemia.

PMID- 20154437
TI  - A right paratracheal air cyst caused by tracheal diverticula.
AB  - A 65-year-old woman presented with pain in her throat and neck. Thin-section
      computed tomography (CT) revealed an air-filled lesion at the right paratracheal
      region and two narrow connections to the trachea. Flexible bronchoscopy showed
      four diverticula 4-5 cm below the vocal cords in the right lateral part of the
      trachea. Consistent with the CT findings, two of the diverticula were deep. A
      radiological barium swallow study and an esopagogastroduodenal endoscopic
      examination revealed no abnormalities. We therefore believe that her right
      paratracheal air cyst is an extension of a tracheal diverticulum. Right-sided
      paratracheal air cysts at the level of the thoracic inlet are a common finding on
      CT and should not be confused with pneumomediastinum in order to avoid
      unnecessary examinations or treatments.

PMID- 20154438
TI  - Severe bivalvular pneumococcal endocarditis and suppurative pericarditis in an
      immunocompetent patient.
AB  - Pneumococcal endocarditis is a very serious and rare clinical entity that results
      in significant morbidity and high mortality rates. It causes severe disease and
      is typically seen in alcoholics and immunocompromised patients. Antimicrobial
      therapy and timely surgery are warranted for optimal management and improving
      outcomes. We present a case of a previously healthy 31-year-old Hispanic man with
      bicuspid aortic valve who developed severe bivalvular pneumococcal endocarditis
      complicated by suppurative pericarditis that was promptly treated with
      antimicrobial therapy and subsequent aortic valve replacement with initial
      favorable clinical and hemodynamic improvement.

PMID- 20154439
TI  - Autoimmune hemolytic anemia accompanied by reactivation of an Epstein-Barr virus
      infection with suppressed CTL response to EBV-infected cells in an elderly man.
AB  - An 88-year-old man with autoimmune hemolytic anemia (AIHA) who had been treated
      with low dose prednisolone developed a sudden worsening of his anemia accompanied
      by reactivation of Epstein-Barr virus (EBV). We established EBV-infected
      spontaneous lymphoblastoid cell lines (LCL), performed an enzyme-linked
      immunosorbent spot assay, and confirmed a significantly suppressed EBV-specific
      cytotoxic T-cell (CTL) response to the LCL. EBV reactivation might have been
      brought about by suppressed CTL activity which could have been due to low dose
      PSL administration or aging. Since the EBV-DNA titer decreased as AIHA improved,
      we concluded that EBV might have played a role in the development of anemia.

PMID- 20154440
TI  - TDP-43 M337V mutation in familial amyotrophic lateral sclerosis in Japan.
AB  - The clinical features of a Japanese family with autosomal dominant adult-onset
      amyotrophic lateral sclerosis (ALS) are reported. Weakness initially affected the
      bulbar musculature, with later involvement of the extremities. Genetic studies
      failed to detect any mutations of the Cu/Zn superoxide dismutase-1 (SOD1) and
      Dynactin1 (DCTN1) genes, but revealed a single base pair change from wild-type
      adenine to guanine at position 1009 in TAR-DNA-binding protein (TDP-43),
      resulting in a methionine-to-valine substitution at position 337. The
      immunohistochemical study on autopsied brain of the proband's aunt showed TDP-43
      positive cytoplasmic inclusions in the anterior horn cells of the spinal cord and
      in the hypoglossal nucleus, as well as glial cytoplasmic inclusions in the
      precentral gyrus, suggesting that a neuroglial proteinopathy was related to TDP
      43. In conclusion, a characteristic clinical phenotype of familial ALS with
      initial bulbar symptoms occurred in this family with TDP-43 M337V substitution,
      the pathomechanism of which should be elucidated.

PMID- 20154441
TI  - Ischemic stroke associated with cough and cold preparation containing
      methylephedrine and supplement containing Chinese herbal drugs.
AB  - Methylephedrine is generally harmless and is contained in many cough and cold
      preparations. Likewise, Chinese herbal drugs are considered to be effective and
      to have few side effects. A 32-year-old woman experienced ischemic stroke
      attributed to concomitant administration of a cough and cold preparation
      containing methylephedrine and a supplement containing Chinese herbal drugs.
      Computed tomography and magnetic resonance imaging of the brain showed acute
      infarctions bilaterally in the cerebellum. Conventional angiography and magnetic
      resonance angiography showed transient stenosis of the left vertebral artery.
      These findings suggested vasospasm or dissection, presumably related to
      hypertension and/or angiitis or vasoconstriction of large cerebral arteries
      leading to local thrombosis as a result of stasis and sympathomimetic-induced
      platelet activation. Combining methylephedrine and Chinese herbal drugs might
      carry a risk of stroke.

PMID- 20154442
TI  - A distinct phenotype of leg hyperreflexia in a Japanese family with Gerstmann
      Straussler-Scheinker syndrome (P102L).
AB  - Gerstmann-Straussler-Scheinker Syndrome (GSS) is an inherited prion disease
      characterized by midlife onset and slowly progression of cerebellar ataxia and
      dementia. We report a distinct phenotype of leg hyperreflexia in a Japanese
      family with GSS. A 38-year-old woman noticed unsteady gait at 33 years of age.
      Afterwards, dysarthria and writing difficulty were appeared. Her family history
      revealed that her grandfather and her mother had a clinical history of
      unsteadiness and mental changes. At 1 year after clinical onset, neurological
      examination showed cerebellar ataxia and leg hyperreflexia. At 4 years after
      onset, she suddenly developed insomnia and nocturnal howling. Her mental status
      disclosed marked disorientation, anxiety and irritability. Muscle stretch
      reflexes were increased in four extremities with Babinski's signs. Remarkable
      dysarthria and cerebellar ataxia were presented. Brain diffusion weighted imaging
      showed extensive hyperintensity signal areas in the cerebral cortex. A point
      mutation of the prion protein gene (PRNP) at codon 102 resulting in the
      substitution of proline by leucine (P102L) was identified. PRNP polymorphism
      exhibited homozygous methionine at codon 129 and homozygous glutamate at codon
      219. She had verbal perseveration, somnolence and myoclonus of lower limbs,
      leading to akinetic mutism at 4 months after neuropsychiatric events. Phenotypic
      hallmark of our patient indicates leg hyperreflexia from an early disease course.
      This neurological sign differs from the previously reported clinical expression
      of Japanese and foreign patients with GSS (P102L). Thus, physicians should pay
      more attention to phenotypic heterogeneity in this prion disease.

PMID- 20154443
TI  - Subacute longitudinal myelitis associated with Behcet's disease.
AB  - In neuro-Behcet's disease (NBD), myelitis is a rare clinical form. We report the
      case of a woman with NBD presenting with unsteady gait and generalized
      spasticity. Spinal magnetic resonance imaging (MRI) showed multiple and confluent
      hyperintensities extending throughout the entire spinal cord on a T2-weighted
      image with some contrast enhancement. High-dose steroid therapy was so effective
      that the myelitis was markedly improved, as shown in the follow-up MRI.
      Longitudinal myelitis involving the entire spinal cord, as seen in our patient,
      has never been described before. This case suggests that NBD could be one of the
      important differential diagnoses of longitudinal myelitis.

PMID- 20154444
TI  - Patient with acute myocardial infarction and Leriche syndrome.

PMID- 20154445
TI  - Symmetrical progressive intracranial calcification in a patient with SLE.

PMID- 20154446
TI  - Syringomyelia in neuromyelitis optica seropositive for aquaporin-4 antibody.

PMID- 20154447
TI  - Smoking-induced alterations in platelet membrane fluidity and Na(+)/K(+)-ATPase
      activity in chronic cigarette smokers.
AB  - AIM: Cigarette smoking is a recognized risk factor for cardiovascular diseases
      and has been implicated in the pathogenesis of atherosclerosis. Platelet
      adhesiveness and aggregation increases as a result of smoking. Cigarette smoking
      modifies haemostatic parameters via thrombosis with a consequently higher rate of
      cardiovascular events, but smoking-induced alterations of platelet membrane
      fluidity and other changes have not been studied. METHODS: Thirty experimental
      and control subjects (mean age 35+/-8) were selected for the study. Experimental
      subjects had smoked 10+/-2 cigarettes per day for 7-10 years. The plasma lipid
      profile, platelet carbonyls, sulfhydryl groups, Na(+)/k(+)-ATPase activity,
      fluidity using a fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), total
      cholesterol and phospholipids as well individual phospholipids were determined.
      RESULTS: Increases in the platelet membrane cholesterol phospholipid (C/P) ratio,
      phosphotidylethanolamine, phosphotidylserine with decreased phosphotidylcholine,
      Na(+)/k(+)-ATPase activity, fluidity and no significant change in
      phosphotidylinositol and sphingomylein, as well as increases in plasma total
      cholesterol, LDL-cholesterol, protein carbonyls with decreased HDL-cholesterol
      and sulfhydryl groups were observed in cigarette smokers. Platelet membrane total
      phospholipids were positively correlated with plasma LDL-cholesterol (r=0.568)
      and VLDL-cholesterol (r=0.614) in cigarette smokers. CONCLUSIONS: Increased
      plasma LDL-cholesterol, VLDL-cholesterol and total cholesterol might have
      resulted in the increased C/P ratio and decreased platelet membrane fluidity of
      cigarette smokers.

PMID- 20154448
TI  - Long-term efficacy of pravastatin therapy in diabetic patients undergoing
      complete coronary revascularization.
AB  - AIM: The long-term effect of statin therapy in diabetic patients after coronary
      revascularization is not well established. Accordingly, we sought to determine if
      whether statin therapy initiated at the time of complete revascularization
      including percutaneous coronary intervention (PCI) and/or bypass surgery reduces
      total and cardiac mortality among diabetic patients. METHODS: We collected data
      from 1,138 consecutive patients who underwent complete revascularization (PCI
      and/or bypass surgery). We then compared all-cause and cardiac mortality rates in
      499 patients with diabetes mellitus of whom 149 (29.9%) were treated with statin
      at the time of revascularization. To adjust the variables that would have been
      related to the decision regarding statin administration, a propensity score was
      computed and multivariate Cox regression was carried out. RESULTS: During follow
      up (8.8+/-2.6 years), 103 patients died (including 43 who died of cardiac
      causes). The Multivariate analysis showed statin therapy to be significantly
      associated with reduced cardiac mortality (HR 0.39, 0.16-0.95; p=0.039), but not
      with all-cause mortality. CONCLUSION: Statin therapy was associated with a
      significantly reduced risk of cardiac mortality in patients with diabetes
      mellitus and coronary artery disease after complete revascularization.

PMID- 20154451
TI  - A case of neonatal cardiac tamponade associated with benign hemangioma.

PMID- 20154450
TI  - Reproducibility and relative validity of food group intake in a food frequency
      questionnaire developed for the Tehran Lipid and Glucose Study.
AB  - OBJECTIVE: To examine the validity and reproducibility of food groups in the semi
      quantitative food frequency questionnaire (FFQ) developed for the Tehran Lipid
      and Glucose Study (TLGS). METHODS: To evaluate the reproducibility of food groups
      included in the FFQ, 132 subjects (61 men and 71 women) aged 20 years or older
      twice completed a 168-item FFQ (FFQ1, FFQ2), with a 14-month interval between
      FFQ1 and FFQ2. Over the 1-year interval, 12 dietary recalls (DRs) were collected
      (1 each month) to assess the validity of the FFQ. Seventeen food groups were
      derived from the FFQ based on methods described in previous studies. Age-adjusted
      and deattenuated Spearman correlation coefficients were used to assess the
      validity of the FFQ. RESULTS: The mean (SD) age and body mass index of subjects
      were 35.5 (16.8) years and 25.5 (5.2) kg/m(2), respectively. Validity correlation
      coefficients ranged from 0.03 (liquid oil) to 0.77 (simple sugars) in men
      (median, 0.44), and from 0.12 (snacks) to 0.79 (simple sugars) in women (median,
      0.37). The energy-adjusted intraclass correlation coefficient, which reflects the
      reproducibility of the FFQ, was 0.51 in men and was highest for tea and coffee
      (0.91); in women it was 0.59 and was highest for simple sugars (0.74). The
      highest percentage of complete agreement and disagreement was observed for snacks
      and desserts (60.6%) and potatoes and dairy products (12.8%), respectively, in
      men, and tea and coffee (62.9%) and legumes (15.7%) in women. CONCLUSIONS: The
      FFQ that was designed for the TLGS was found to be reliable and valid for
      assessing the intake of several food groups.

PMID- 20154449
TI  - Impact of lifestyle on overall cancer risk among Japanese: the Japan Public
      Health Center-based Prospective Study (JPHC Study).
AB  - In Japan, cancer has long been recognized as a major component of the overall
      pattern of disease. Currently, there is a need to implement practical control
      measures with specific numerical targets appropriate for the Japanese population.
      Using data from the Japan Public Health Center-based Prospective Study, the
      author estimated the impact of major risk factors on overall cancer risk among a
      Japanese population. These risk factors included tobacco smoking, alcohol
      drinking, body mass index, history of diabetes, physical activity, and metabolic
      factors and their aggregates. The results show that tobacco smoking and heavy
      alcohol drinking were significantly positively associated with overall cancer
      risk, and that total physical activity was significantly inversely associated
      with the risk of cancer. Although people with a history of diabetes may be at
      increased risk of cancer, extreme body mass index and metabolic factors in the
      aggregate had little impact on overall cancer risk in the Japanese population.

PMID- 20154452
TI  - The mechanism of mineralization and the role of alkaline phosphatase in health
      and disease.
AB  - Biomineralization is the process by which hydroxyapatite is deposited in the
      extracellular matrix. Physiological mineralization occurs in hard tissues,
      whereas pathological calcification occurs in soft tissues. The first step of
      mineralization is the formation of hydroxyapatite crystals within matrix vesicles
      that bud from the surface membrane of hypertrophic chondrocytes, osteoblasts, and
      odontoblasts. This is followed by propagation of hydroxyapatite into the
      extracellular matrix and its deposition between collagen fibrils. Extracellular
      inorganic pyrophosphate, provided by NPP1 and ANKH, inhibits hydroxyapatite
      formation. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes
      pyrophosphate and provides inorganic phosphate to promote mineralization.
      Inorganic pyrophosphate, pyridoxal phosphate, and phosphoethanolamine are thought
      to be the physiologic substrates of TNAP. These accumulate in the event of TNAP
      deficiency, e.g., in cases of hypophosphatasia. The gene encoding TNAP is mapped
      to chromosome 1, consists of 12 exons, and possesses regulatory motifs in the 5'
      untranslated region. Inhibition of TNAP enzymatic activity suppresses TNAP mRNA
      expression and mineralization in vitro. Hypophosphatasia is an inherited systemic
      bone disease characterized by hypomineralization of hard tissues. The phenotype
      of hypophosphatasia is varied. To date, more than 200 mutations in the TNAP gene
      have been reported. Knockout mice mimic the phenotypes of severe
      hypophosphatasia. Among the mutations in the TNAP gene, c.1559delT is frequent in
      the Japanese population. This frameshift mutation results in the expression of an
      abnormally long protein that is degraded in cells. DNA-based prenatal diagnosis
      using chorionic villus sampling has been developed, but requires thorough genetic
      counseling. Although hypophosphatasia is untreatable at present, the recent
      success of enzyme replacement therapy offers promise. The problems presented by
      impaired mineralization in age-related chronic diseases, such as pathologic
      calcification and decreasing physiological mineralization are growing in
      importance. Strategies for preventing pathologic calcification using TNAP and
      NPP1 are in development. A nutrigenomic approach, based on the relationship
      between TNAP gene polymorphism and bone mineral density, is also discussed.

PMID- 20154453
TI  - A new look at criteria for damage control surgery.
AB  - BACKGROUND: Several reports have validated the criteria for damage control
      surgery (DCS). However, although metabolic acidosis and body temperature can be
      measured quickly, tests for predicting the severity of coagulopathy require
      special laboratory equipment and take 15 to 30 minutes. Such delays could be life
      threatening for patients requiring DCS. The aim of this study was to establish
      simplified and practical criteria to enable rapid decision-making regarding the
      need for DCS. METHODS: Thirty-four consecutive patients with unstable
      hemodynamics after initial fluid resuscitation who had undergone DCS for severe
      abdominal or pelvic injuries were retrospectively analyzed. The patients'
      characteristics, clinical courses, laboratory data, and outcomes were reviewed
      using the data contained in their medical records. RESULTS: The overall survival
      rate was 55.9% (survivors group: n=19; nonsurvivors group: n=15), which was
      similar to the calculated mean probability of survival (Ps=0.5671). At the start
      of surgery, the systolic blood pressure (SBP) was less than 90 mm Hg in all cases
      in which surgery failed, and the mean SBP in the nonsurvivors group (69.6 +/-
      14.8 mm Hg) was significantly lower than that in the survivors group (93.2 +/-
      22.9 mm Hg, p=0.006). Except in two cases, the value of the base excess in the
      nonsurvivors group was less than -7.5 mmol/L, and the mean base excess (-11.5 +/-
      5.3 mmol/L) in the nonsurvivors group was significantly less than that in the
      survivors group (-5.5 +/- 4.9 mmol/L, p=0.008) at the start of surgery. The core
      temperature at the start of surgery was less than 35.5 degrees C in all cases in
      the nonsurvivors group. On the basis of these results, three indicators (SBP less
      than 90 mm Hg, base excess less than -7.5 mmol/L, and core temperature less than
      35.5 degrees C at the start of surgery) were identified. The success rate of DCS
      in patients who possessed all three indicators (28.6% ) was significantly lower
      than that in patients who did not possess all three indicators (75.0%; p=0.014).
      CONCLUSION: Our results indicate that surgeons should decide to perform DCS when
      only one or two criteria defined in this study are met and should not wait for
      all three criteria. Although our proposed criteria are not strict and may broaden
      the indications for DCS, leading to an increase in the number of DCS procedures,
      saving the lives of patients who have sustained severe torso trauma must be the
      priority; 'over-triage' may be acceptable in situations where an appropriate
      decision-making protocol has been followed.

PMID- 20154454
TI  - One-year evaluation of combined treatment with an intranasal corticosteroid and
      montelukast for chronic rhinosinusitis associated with asthma.
AB  - OBJECTIVES: Chronic rhinosinusitis associated with asthma is often difficult to
      treat effectively with intranasal corticosteroids alone. Thus, the aim of this
      study was to evaluate the effectiveness of combination treatment with an
      intranasal corticosteroid and a leukotriene-receptor antagonist (montelukast) in
      reducing the size of nasal polyps. METHODS: The subjects of this study were 20
      patients with chronic rhinosinusitis associated with adult-onset asthma, which
      was being treated with inhaled corticosteroids. All patients were treated with
      intranasal fluticasone propionate, 200 microg/day, and montelukast, 10 mg/day,
      for 1 year. The size of nasal polyps and the score of sinus shadows were assessed
      with nasal endoscopy and computed tomography (CT), respectively, before and after
      treatment. The peripheral blood eosinophil counts were also evaluated before and
      after treatment. RESULTS: Nasal polyps were significantly smaller after both 6
      months (p<0.01) and 12 months of treatment (p<0.01) than before treatment. The
      decrease in the shadow score was statistically significant after both 6 months
      (p<0.01) and 12 months of treatment (p<0.01). Significant reductions in
      peripheral blood eosinophil counts were also seen after both 6 months (p<0.05)
      and 12 months of treatment (p<0.01). A significant correlation was found between
      the rate of change in the peripheral blood eosinophil count and that in the CT
      score after both 6 months (r=0.578, p=0.012) and 12 months (r=0.625, p=0.007).
      CONCLUSION: Combined treatment with intranasal fluticasone propionate and
      montelukast, for at least 1 year, is effective for chronic rhinosinusitis
      associated with adult-onset asthma.

PMID- 20154455
TI  - Relapsing autoimmune pancreatitis in a 14-year-old girl.
AB  - We present a case of acute pancreatitis in a 14-year-old girl which fulfilled the
      diagnostic criteria of autoimmune pancreatitis (AIP) and responded to
      corticosteroid therapy. Imaging studies revealed that the main pancreatic duct
      was narrow in the head of the pancreas but had been dilated in the body at an
      earlier stage. The pancreatitis recurred twice when the prednisolone dose was
      reduced to 10 mg or less but responded each time to an increased dose and has
      been kept under control with low-dose prednisolone therapy for 3 years since
      onset. Repeated magnetic resonance cholangiopancreatography during steroid
      therapy revealed an improvement of the narrowing of the main pancreatic duct in
      the head and dilation of the duct in the body. AIP in younger patients has
      distinct clinical features, such as presentation with epigastralgia, back pain
      without jaundice, and elevated serum amylase levels. The serum level of IgG4 is
      rarely increased in young patients, indicating a different disease mechanism than
      for cases in elderly patients. Given the excellent response of this condition to
      steroid therapy, AIP should be considered even in young children and adolescents
      when the diagnosis of idiopathic pancreatitis is suggested.

PMID- 20154456
TI  - Microscope-assisted reduction clitoroplasty used to treat two patients with
      clitoromegaly.
AB  - We report 2 cases of clitoromegaly, 1 in a patient with true hermaphroditism, and
      the other in a patient with adrenogenital syndrome. Both were treated surgically
      with reduction clitoroplasty. There are 3 different clitoroplasty procedures:
      clitorectomy, clitoral recession, and reduction clitoroplasty. Reduction
      clitoroplasty with preservation of the neurovascular bundle is considered
      superior in terms of formation of the external genitals and sensation. However,
      the disadvantages are that detachment of the neurovascular bundle from the
      clitoral shaft is difficult and that there is a high possibility of sensory and
      blood flow disorders in the clitoris. In an attempt to achieve safe and reliable
      surgical manipulation, we used a surgical microscope (OPMI 6-SDFC, Carl Zeiss
      Surgical GmbH, magnification x8) to detach the neurovascular bundle from the
      clitoral shaft in our 2 patients. Our impression is that our efforts were
      extremely effective. Furthermore, our experience leads us to believe that the
      procedure for neurovascular bundle detachment required in reduction clitoroplasty
      is not particularly difficult if performed with a surgical microscope by a
      plastic surgeon who regularly performs microsurgery. Because the procedure can be
      performed simply and safely, we believe that reduction clitoroplasty with
      preservation of the neurovascular bundle is the best overall of the 3
      clitoroplasty procedures.

PMID- 20154457
TI  - A case of severe mental and developmental retardation associated with 14q
      terminal monosomy/5q terminal trisomy.
AB  - I previously described the case of a 19 year-old female with severe mental
      retardation, developmental retardation, microcephalus, short stature, bilateral
      microphthalmia, ptosis and blepharophimosis(1). Now, I present clinical
      descriptions of her half-siblings, who have a different father. Subtelomeric
      fluorescence in situ hybridization (FISH) analysis of the proband demonstrated 5q
      terminal trisomy and 14q terminal monosomy. I presume that her mother harbors a
      balanced translocation between the terminal of chromosome 5q and 14q. I suggest
      that familial cases of mental retardation and dysmorphic features should be
      screened for terminal chromosomal abnormalities by FISH or comparative genomic
      hybridization (CGH), even if G-banding analysis or high-resolution chromosome
      analysis is normal.

PMID- 20154458
TI  - Expression and function of B7 family molecules in hematologic malignancies.

PMID- 20154459
TI  - The molecular mechanism of glucose metabolism hampered by p53 tumor suppressor
      protein.

PMID- 20154460
TI  - Development of antitumor immunity by oral vaccination with tumor antigen and
      cholera toxin.

PMID- 20154461
TI  - Neuropilin-1, as a new therapeutic target in human pancreatic cancer.

PMID- 20154462
TI  - Brain protection and regeneration therapy for delayed neuronal injury in
      neurological disorders.

PMID- 20154463
TI  - The importance of assessment of endothelial function according to the time course
      of flow-mediated dilation of the brachial artery.

PMID- 20154464
TI  - New therapeutic strategy for intractable pancreatic cancer and its fundamental
      research.

PMID- 20154465
TI  - Biopsychosocial factors and musculoskeletal symptoms of the lower extremities of
      saleswomen in department stores in Thailand.
AB  - OBJECTIVES: To identify individual, work-related physical and psychosocial
      factors associated with the self-reported prevalence of musculoskeletal symptoms
      in the hip, knee and ankle/foot of saleswomen in department stores in Thailand.
      METHODS: A cross-sectional survey was conducted in which 1,310 saleswomen in 18
      department stores received a self-administered questionnaire. Returns were 1,200
      (92%) questionnaires, and after screening for exclusion criteria, 1,189
      saleswomen were found to be eligible for the study. RESULTS: Having a child,
      number of working hours per day, frequency of body twisting during work and self
      rated perception of light intensity in the workplace were each significantly
      associated with the prevalence of experiencing hip symptoms. Significant
      associations were found between age, number of hours per day required to stand or
      walk and self-rated perception of temperature in the workplace, and the
      prevalence of experiencing knee symptoms. The number of working hours per day and
      working days per week as well as frequency of working in static postures and rest
      breaks during work were each significantly related to the prevalence of
      experiencing ankle/foot symptoms. CONCLUSIONS: Among saleswomen, various
      individual and work-related physical factors were identified as risks and
      preventive factors for musculoskeletal symptoms in the lower extremities. Further
      research should focus on these modifiable factors in order to develop effective
      strategies for reducing the occurrence of such symptoms in saleswomen.

PMID- 20154466
TI  - Job stress and mental health among workers in Asia and the world.

PMID- 20154467
TI  - Recent development of two chitinase inhibitors, Argifin and Argadin, produced by
      soil microorganisms.
AB  - Chitin, the second most abundant polysaccharide in nature, occurs in fungi, some
      algae and many invertebrates, including insects. Thus, chitin synthesis and
      degradation could represent specific targets for fungicides and insecticides.
      Chitinases hydrolyze chitin into oligomers of N-acetyl-D-glucosamine at key
      points in the life cycles of organisms, consequently, chitinase inhibitors have
      become subject of increasing interest. This review covers the development of two
      chitinase inhibitors of natural origin, Argifin and Argadin, isolated from the
      cultured broth of microorganisms in our laboratory. In particular, the practical
      total synthesis of these natural products, the synthesis of lead compounds via
      computer-aided rational molecular design, and discovery methods that generate
      only highly-active compounds using a kinetic target(chitinase)-guided synthesis
      approach (termed in situ click chemistry) are described.

PMID- 20154468
TI  - Recent advances in rice genome and chromosome structure research by fluorescence
      in situ hybridization (FISH).
AB  - Fluorescence in situ hybridization (FISH) is an effective method for the physical
      mapping of genes and repetitive DNA sequences on chromosomes. Physical mapping of
      unique nucleotide sequences on specific rice chromosome regions was performed
      using a combination of chromosome identification and highly sensitive FISH.
      Increases in the detection sensitivity of smaller DNA sequences and improvements
      in spatial resolution have ushered in a new phase in FISH technology. Thus, it is
      now possible to perform in situ hybridization on somatic chromosomes, pachytene
      chromosomes, and even on extended DNA fibers (EDFs). Pachytene-FISH allows the
      integration of genetic linkage maps and quantitative chromosome maps.
      Visualization methods using FISH can reveal the spatial organization of the
      centromere, heterochromatin/euchromatin, and the terminal structures of rice
      chromosomes. Furthermore, EDF-FISH and the DNA combing technique can resolve a
      spatial distance of 1 kb between adjacent DNA sequences, and the detection of
      even a 300-bp target is now feasible. The copy numbers of various repetitive
      sequences and the sizes of various DNA molecules were quantitatively measured
      using the molecular combing technique. This review describes the significance of
      these advances in molecular cytology in rice and discusses future applications in
      plant studies using visualization techniques.

PMID- 20154470
TI  - Establishment of a concept of visceral fat syndrome and discovery of adiponectin.
AB  - Although obesity is a major background of life style-related diseases such as
      diabetes mellitus, lipid disorder, hypertension and cardiovascular disease, the
      extent of whole body fat accumulation does not necessarily the determinant for
      the occurrence of these diseases. We developed the method for body fat analysis
      using CT scan and established the concept of visceral fat obesity, in other word
      metabolic syndrome in which intra-abdominal visceral fat accumulation has an
      important role in the development of diabetes, lipid disorder, hypertension and
      atherosclerosis. In order to clarify the mechanism that visceral fat accumulation
      causes metabolic and cardiovascular diseases, we have analyzed gene expression
      profile in subcutaneous adipose tissue and visceral adipose tissue. From the
      analysis, we found that adipose tissue, especially visceral adipose tissue
      expressed abundantly the genes encoding bioactive substances such as cytokines,
      growth factors and complements. In addition to known bioactive substances, we
      found a novel collagen-like protein which we named adiponectin. Adiponectin is
      present in plasma at a very high concentration and is inversely associated with
      visceral fat accumulation. Adiponectin has anti-diabetic, anti-hypertensive and
      anti-atherogenic properties and recent studies revealed that this protein has an
      anti-inflammatory and anti-oncogenic function. Therefore hypoadiponectinemia
      induced by visceral fat accumulation should become a strong risk factor for
      metabolic and cardiovascular diseases and also some kinds of cancers.In this
      review article, I would like to discuss the mechanism of life style-related
      diseases by focusing on the dysregulation of adiponectin related to obesity,
      especially visceral obesity.

PMID- 20154471
TI  - [Aberrant methylation of circulating DNA for prediction of chemo-sensitivity of
      non-small cell lung cancer].
AB  - In advanced lung cancer, there are few opportunities to obtain a
      histopathological specimen, so it is quite difficult to predict chemo-sensitivity
      in and individual case. The reason is that surgical resection of the primary
      region of an advanced lung cancer is not common, and an endoscopically obtained
      sample is occasionally insufficient for accurate pathological classification.
      Circulating DNA is a potential solution in this situation. Circulating DNA
      derived from advanced cancer has been utilized for various studies, and a recent
      report indicated that DNA methylation of circulating DNA is useful for prediction
      of the chemosensitivity of non-small cell lung cancer. In this review, the author
      discusses the recent situation of cancer chemotherapy for non-small cell lung
      cancer, presents an outline of epigenetics, epigenetic change in lung cancer and
      a preliminary study of circulating DNA methylation.

PMID- 20154469
TI  - Molecular approach to human leukemia: isolation and characterization of the first
      human retrovirus HTLV-1 and its impact on tumorigenesis in adult T-cell leukemia.
AB  - Molecular biology of mouse and chicken retroviruses had identified oncogenes and
      provided a revolutionary concept in understanding of cancers. A human retrovirus
      was established during 1980-1982 in linkage with a unique human leukemia,
      concurrently in Japan and USA. This review covers our efforts on the discovery of
      new retrovirus, Human T-cell Leukemia Virus Type 1 (HTLV-1), first introducing to
      a new class of retroviruses with a unique regulatory factors, Tax and Rex. Then
      it is followed by analyses of molecular interaction of the vial Tax with cellular
      machineries involved in the pathogenesis of Adult T-cell Leukemia (ATL). And then
      a probable mechanism of pathogenesis of ATL is proposed including recent findings
      on HBZ after our efforts.

PMID- 20154472
TI  - [Diagnosis and treatment of liver metastases].
AB  - Approximately 35-60% of patients with colorectal cancers will develop liver
      lesions during their life span. Previously colorectal liver metastases have
      traditionally been categorized as incurable systemic disease. However, the
      introduction of new chemotherapeutic regimens(e.g. FOLFOX or FOLFIRI)and recent
      technical innovations(e. g. staged hepatic resection and percutaneous
      transhepatic portal embolization)has allowed us to perform hepatic resection with
      curative intent. Additionally, a neoadjuvant strategy has expanded the criteria
      for liver resection, and more active molecular therapeutic agents are now
      available. As a result, a recent advancement has enhanced the overall 5-year
      survival from 30% to 58% for colorectal liver metastases. Despite these facts,
      many patients still experience a recurrence after hepatic resection. Modern
      treatment of colorectal liver metastases requires a multimodal approach to
      increase the number of patients who may benefit from surgical treatment of
      colorectal liver metastases.

PMID- 20154473
TI  - [Surgical management of pulmonary metastases].
AB  - Because lung metastasis from a solid malignant tumor is a distant and
      hematogenous metastasis, its prognosis is generally dismal. Therefore, the
      indications of local therapy such as surgical resections of lung metastasis
      remain very controversial. However, in some cases, the metastasis of tumor cells
      from the primary site can be confined to the lungs before systemic and
      disseminated disease. Surgical resection could be a curative treatment at this
      stage of lung metastasis. A smaller number of metastases, long disease-free
      survival time, and no lymph node metastasis are the predictive factors for good
      prognosis after resection of lung metastasis. However, there have been no
      criteria for the indications of lung metastasectomies. Indications and outcomes
      of surgical resection for lung metastasis depend on each primary malignancies.
      Wedge resection of the lung is thought to be an appropriate procedure for the
      resection of metastatic lung tumors. Video assisted thoracoscopic resection is
      now widely used, however, controversy persists about whether this technique is
      appropriate approach for the patients undergoing metastasectomy with curative
      intent because the lack of palpation may be a cause of missing small metastatic
      lung tumors despite the advent of high resolution CT. There is no randomized
      trial assessing whether there is any difference in survival after metastasectomy
      with versus without manual lung palpation. Recent progress of chemotherapy, such
      as FOLFOX for colorectal cancer, could change the indications and outcome of
      surgical resection of metastatic lung tumors. In addition, newly developed
      radiofrequency ablation came to be performed as local therapy in some centers. We
      should decide the timing of resection considering the schedule of chemotherapy,
      so close corporation of surgeons and physicians is essential for managing
      metastatic lung tumors.

PMID- 20154475
TI  - [Diagnosis and treatment for bone metastases--multidisciplinary team medicine by
      cancer board].
AB  - With the recent progress in cancer treatment making longer survival possible, the
      need of treatment for bone metastases has become indispensable to assure patient
      QOL(quality of life). Treatment and prevention of fracture and spinal cord injury
      are very important not only to maintain good QOL but also to improve survival.
      Early diagnosis of the risks and the prevention and treatment of fracture and
      spinal cord injury are necessary. An orthopedics-based team approach to
      establishing an effective and intensive diagnosis and treatment system for bone
      metastases is called for Cancer Board.

PMID- 20154474
TI  - [Multidisciplinary management of brain metastases].
AB  - Metastatic brain tumors are increasingly important determinants of survival and
      quality of life in patients with cancer. The management of brain metastases is
      directed by prognostic factors, including the Karnofsky Performance Status, age,
      pathological diagnosis, number of brain metastases, and systemic condition. Most
      metastatic brain tumors are treated by surgery, radiosurgery, and/or whole brain
      radiation therapy. Adequate management strategy cannot be standardized to a
      single paradigm. Current diagnostic modalities and techniques are reviewed, and
      data of several clinical studies are presented to help physicians and surgeons
      make informed decisions about the benefits and risks of approaches.

PMID- 20154476
TI  - [Skin metastasis].
AB  - Clinical and histopathological findings of skin metastasis show much variation.
      When skin metastatic carcinoma is diagnosed by histopathologic evaluation of the
      involved skin, the treatment must be started as soon as possible after immediate
      identification of the primary internal organ and the stage of the disease.
      Furthermore, one must investigate and infer the type of primary tumor from the
      previous history of internal malignancy, immunohistochemical findings and/or the
      results of some imaging. When a primary organ is confirmed, consultation with the
      department specializing in primary tumors is required for close inspection and
      treatment. When the primary origin is unidentified, detailed discussion is
      required about the diagnosis and therapeutic examination among the specialized
      departments including dermatology.

PMID- 20154477
TI  - [Effectiveness of concomitant therapy with S-1, nedaplatin, and radiation for
      laryngeal cancer].
AB  - Laryngeal cancer occurs more frequently in head and neck cancers, so there are a
      number of reports regarding the treatment results,wherein the therapeutic
      strategy and results are stable to some extent. However, due to the spread of
      chemoradiotherapy, there are differences in the larynx preservation rates for T2
      and T3 cases, depending on the facility. Our department has been administering
      chemoradiotherapy for advanced cancer based on the perspective of conserving the
      organ and the function. We herein report our examination of 20 laryngeal cancer
      cases receiving concomitant therapy with S-1, Nedaplatin, and radiation
      (hereinafter, referred to as SN therapy) in our department from April 2005 to
      December 2008. The resulting complete response (CR) rate for the SN therapy was
      82.4%, excluding T4 cases. Due to their refusal of surgery, 2 of 3 cases in which
      the SN therapy had been administered for T4 cases receiving SN therapy showed CR,
      wherein the CR rate in all cases after the SN therapy was 80. 0%. The larynx
      preservation rate after the SN therapy was 94.1%.

PMID- 20154479
TI  - [Combination therapy of S-1 and 24-h infusion of cisplatin after palliative
      gastrectomy for stage IV gastric cancer].
AB  - We prospectively analyzed the adverse effects and outcomes of 15 patients with
      stage IV gastric cancer who underwent palliative gastrectomy from December, 2002
      to May, 2008 and subsequently received combination therapy of S-1 and 4-h
      infusion of cisplatin. The National Cancer Institute common toxicity criteria
      (version 3. 0) were applied to evaluate the adverse effects of this therapy, and
      the Kaplan-Meier method was used to plot the survival curve. The side effects
      most frequently observed were anorexia (grade 3; 33%), although one case of grade
      4 who was easily fatigued was noted during the first course and could not receive
      further courses of this therapy. The 2-year survival rate was 33% and median
      survival time was 31 months. It has been suggested that 24-h infusion of
      cisplatin combined with oral S-1 after reduction surgery might improve survival
      in patients with stage IV gastric cancer.

PMID- 20154478
TI  - [Chemotherapy-induced myelosuppression and treatment efficacy in limited-stage
      disease small cell lung cancer].
AB  - We examined the association between chemotherapy-induced myelosuppression and
      prognosis in limited-stage disease small cell lung cancer (LD SCLC). We
      retrospectively analyzed 76 patients with LD SCLC who received combination
      cisplatin or carboplatin of etoposide or irinotecan. Patients were categorized
      into two groups (grade 0 to 2 or grade 3 to 4) according to the worst
      neutropenia, anemia, or thrombocytopenia during first-line chemotherapy and were
      analyzed for overall survival (OS) and time to progression (TTP). From univariate
      analysis, OS was significantly better in patients who developed grade 0 to 2
      anemia or thrombocytopenia than those who developed grade 3 to 4. In addition,
      performance status, neuron-specific enolase (NSE), and pro-gastrin-releasing
      protein were identified as prognostic factors. By multi-variate analysis, NSE was
      an independent prognostic factor for OS. There were no independent prognostic
      factors for TTP. Myelosuppression during chemotherapy is not a prognostic factor
      in LD SCLC. Our results show doses of platinum doublet chemotherapy were adequate
      in patients with LD SCLC.

PMID- 20154480
TI  - [Problems of adjuvant chemotherapy with S-1 for gastric cancer].
AB  - From results of ACTS-GC,postoperative adjuvant chemotherapy,administration of S-1
      for one year has become the standard for gastric cancer of Stage II and III
      except T1. We inspected problems of adjuvant chemotherapy by S-1 by dose rate, an
      adverse event,and compliance. For the period from July 2006 to December
      2008,among 41 cases of stage II/stage III gastric cancer, S-1 was as started as
      adjuvant therapy by for 28 cases (68.3%). Among 14 cases (63.6%) considered able
      to complete S-1 treatment for one year, 7 cases (31.8%) had to have their dose
      reduced or their administration schedule changed. No adverse event of grade 3/4
      was found, but cancellation or reduced dose was necessary due to anorexia,
      malaise, diarrhea, severe skin reaction, and leukopenia resulting from
      myelosuppression. Thirteen patients took no S-1, and two (4.9%) of them took UFT,
      while 11 cases (26.8%) became a no-treatment follow-up group for reasons of age,
      coexisting symptoms and other reasons. The problem in the future is to improve
      compliance, and to establish a treatment strategy for patients who do not meet
      administration criteria and for patients for whom continuation of drug
      administration is impossible.

PMID- 20154481
TI  - [Our experiences of best supportive care for gastric cancer patients].
AB  - BACKGROUND: The literature contains only a small number of reports concerning
      best supportive care(BSC)in gastric cancer. With the progress of social
      healthcare systems supporting medical care at home, the quality and performance
      of BSC at present are different from those in the mid-1990s, when the previous
      reports were published. We evaluated the quality and performance of BSC in
      gastric cancer patients in collaboration with visiting nurses. PATIENTS AND
      METHODS: This study comprised 17 gastric cancer patients receiving BSC between
      March 2005 and April 2009. Baseline characteristics were age, sex, performance
      status, and main disease site at entry. Except for one patient who died of other
      than gastric cancer, types of nutritional support whenever needed during the BSC
      period were divided into two categories; drip infusion through peripheral vein
      (peripheral group, n=7) and parenteral or enteral nutrition through a central
      venous catheter or gastrostomy (hyperalimentation group, n=9). The main outcome
      measures were overall survival and survival according to the type of nutritional
      support, as well as quality and performance of BSC. RESULTS: Mean age and mean PS
      were 76 years old and 2. 9, respectively, with incidences of > or =75 years old
      and PS> or =3 accounting for 71% and 59%, respectively. Overall MST was 175 days,
      which was longer than earlier reported. MST of the hyperalimentation group (190
      days)was significantly (p<0.04) longer than that of the peripheral group.
      Fourteen patients (88%) could stay at home during at least part of the BSC
      period, and among them, 10 patients received home visiting care by a doctor
      and/or nurse, and 7 patients (70%) died at home. Eight patients (89%) in the
      hyperalimentation group received home care visits. CONCLUSIONS: These results
      suggest that home care hyperalimentation by visiting nurses prolongs BSC patient
      survival in gastric cancer. Domiciliary care realizes hyperalimentation and
      provides comprehensive home-care during BSC period.

PMID- 20154482
TI  - [Adjuvant surgery for advanced gastric cancer].
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy
      of(adjuvant)surgery following the response to chemotherapy for advanced gastric
      cancer. SUBJECTS AND METHODS: The subjects were 20 advanced gastric cancer
      patients who had undergone gastrectomy following the response to combination
      chemotherapy with docetaxel and S-1 from September 2003 to December 2008. They
      consisted of 14 men and 6 women, with a median age of 58. 8, who received
      combination chemotherapy with docetaxel and S-1 according to the following
      regimen: S-1, 80 mg/m2, was administered on 14 consecutive days followed by a 7
      day rest period, and docetaxel, 40 mg/m2, was administered on day 1. RESULTS: The
      average treatment was 4. 4 courses. They consisted of 17 PR and 3 SD. The median
      overall survival was 855 days. 2-year and 3-year survival was seen in 80% and 54.
      9% of patients, respectively, following macroscopically curative operation.
      Median survival of patients with liver metastasis and peritoneal dissemination
      was 865 days and 510 days, respectively. CONCLUSION: Adjuvant surgery might be
      effective in advanced gastric cancer patients except for cases of peritoneal
      dissemination.

PMID- 20154483
TI  - [Analysis of blood concentrations following oral administration of beclomethasone
      dipropionate for gut GVHD].
AB  - In this study, we investigated the level of gut absorption following oral
      beclomethasone dipropionate (BDP) administration by measuring the blood
      concentration of its metabolites measured by LC-MS/MS using the HPLC method. Five
      patients who were administered BDP orally for gut GVHD were included. The blood
      concentrations of beclomethasone-17-monopropionate (17BMP), which is one of the
      active metabolites of BDP, were 618 approximately 1, 749 pg/mL in 4 of the
      studied 5 patients, which was comparable to that after inhalation of BDP;
      however, it was relatively higher in one patient (2,439+/-161 pg/mL). As the
      blood concentration of 17BMP in this study patient was higher compared with
      healthy volunteers administered a single oral BDP 4 mg, GVHD patients might have
      a higher concentration than healthy volunteers. Given that a higher grade of gut
      GVHD was associated with a higher blood level of 17BMP, BDP absorption might be
      associated with gut mucosal injury. Thus, the systemic adverse effect following
      oral BDP administration might not be negligible especially in gut GVHD patients.

PMID- 20154484
TI  - [Transcatheter arterial chemoembolization with a lipophilic platinum complex SM
      11355(miriplatin hydrate)--safety and efficacy in combination with embolizing
      agents].
AB  - SM-11355 is a cisplatin derivative with high affinity for iodized ethyl esters of
      fatty acids of poppyseed oil. Clinical trials have shown that SM-11355 is
      effective for treatment of hepatocellular carcinoma. Transcatheter arterial
      chemoembolization is commonly used in combination with embolizing agents, but
      concomitant use of SM-11355 and embolizing agents has not been evaluated in
      previous trials. In this study, the safety and efficacy of SM-11355 in
      combination with embolizing agents were investigated in 10 patients with
      hepatocellular carcinoma. An anti-tumor effect of TE4 was achieved in 4 of 9
      patients and no serious adverse events were observed, indicating that this
      therapy can be used safely for hepatocellular carcinoma.

PMID- 20154485
TI  - [Clinicopathological features of endometrial carcinoma in tamoxifen- and
      toremifene-treated breast cancer patients].
AB  - OBJECTIVE: Estrogen is involved in the development of breast and endometrial
      cancers, and tamoxifen, an antiestrogen, is associated with an increased risk of
      endometrial cancer. Recently, tamoxifen use is suggested to be associated with
      the development of aggressive endometrial tumors. We performed a retrospective
      study to clarify the effects of tamoxifen (TAM) and toremifene (TOR) on
      clinicopathological features of endometrial cancer subsequently developed in
      breast cancer patients. METHODS: Endometrial cancer patients diagnosed at our
      institution from 2000 through 2008 were studied. RESULTS: Of 194 patients with
      endometrial cancer, 18 (9.3%) developed breast cancer before endometrial cancer
      diagnosis. Mean age was 66 years, and the median time interval between breast and
      endometrial cancer diagnosis was 10 years (range, 1.5 -32 years). Nine patients
      developed aggressive tumors(serous, clear cell, small cell carcinoma, and
      carcinosarcoma), and the remaining nine developed endometrioid tumor. Patients
      with aggressive tumor had a lower 5-year disease-specific survival (0% vs 88%,
      p<0.01). Ten patients had used TAM and/or TOR, and six had not; aggressive tumors
      developed in six of 10 TAM/TOR users, and in one of six nonusers (p=0.15), and
      the 3-year disease-specific survival rate was not different between TAM/TOR users
      and nonusers (62% vs 53%, p=0.84). Time intervals from breast cancer and
      endometrial cancer diagnosis were 10-16 years for TAM users and 5-6 years for TOR
      users (p=0.02). CONCLUSION: Tamoxifen/toremifene use for breast cancer did not
      affect the prognosis of subsequent endometrial cancer in our small study;
      however, further studies were warranted. The use of toremifene may be associated
      with a shorter interval from breast cancer to endometrial cancer diagnosis
      compared to tamoxifen.

PMID- 20154486
TI  - [Preparation of standard protocol for cancer pain control and evaluation of its
      clinical effectiveness].
AB  - In order to promote the appropriate control of cancer pain by opioids, we
      distributed a pocket-sized protocol pamphlet on cancer pain control and opioid
      prescription to the medical staff of Nagoya University Hospital. In this study,
      we examined whether the prescription rate of opioids for rescue use, antiemetics
      for preventing adverse effects, and the rate of increase of regular opioid dosage
      were increased after distribution to evaluate its utility. Rescue opioid
      prescriptions, increase of regular opioid dosage and antiemetic prescription rate
      after distribution were all significantly increased, compared with before
      distribution. Furthermore, the frequency of nausea and vomiting was reduced by
      the use of prophylactic antiemetics. These results suggest that distribution of
      this protocol for cancer pain control may contribute to appropriate pain
      management.

PMID- 20154487
TI  - [Evaluation of pain reduction upon injecting goserelin acetate using an ice
      pack].
AB  - LH-RH agonist is the key drug in hormonal therapy for premenopausal patients with
      breast cancer. It is important to reduce the pain related to injecting the LH-RH
      agonist, because patients must continue the medication for several years. We
      developed a way to reduce the pain by cooling the needle injecting site with a
      frozen ice pack. 18 premenopausal postoperated women filled out a questionnaire
      on the severity of pain upon injecting Goserelin acetate compared with the pain
      without this cooling method and pretreatment. We estimated the pain by a
      Numerical Rating Scale(NRS). The NRS scores of this cooling method revealed the
      pain to be significantly less than by control method(p<0. 005). This cooling
      method could be useful for the reduction of pain upon injecting the LH-RH
      agonist.

PMID- 20154488
TI  - [A case of complete response treated by S-1 with concurrent radiotherapy for a
      gefitinib-resistant non-small cell lung cancer patient].
AB  - A 35-year-old woman with a clinical diagnosis of stage T2N2M0 lung adenocarcinoma
      received 3 courses of preoperative chemotherapy with cisplatin and docetaxel. The
      treatment response was no change. A left inferior lobectomy with mediastinal and
      hilar lymph-node dissection (ND2a) was performed. The pathological diagnosis was
      stage T2N2M0 lung cancer. Gefitinib was administered postoperatively. After 2
      months of oral treatment, gefitinib was discontinued because of enlarged
      subcarinal lymph nodes and an elevated level of serum Sialyl LewisX-i antigen
      (SLX). Starting 4 months after surgery, the mediastinum was irradiated with a
      total dose of 50 Gy. Chemotherapy with S-1 was started 5 months after surgery. S
      1 was administered in a dose of 100 mg/day in two divided doses for 4 weeks,
      followed by 2 weeks of rest. The patient received 6 courses of chemotherapy with
      S-1, without increasing the dose. The enlarged mediastinal lymph nodes
      disappeared, and the serum SLX level returned to normal. The patient had a
      complete response, and was subsequently followed on an outpatient basis while
      receiving oral UFT. More than 36 months have elapsed since surgery, with no
      evidence of recurrence.

PMID- 20154489
TI  - [Complete response in a case of advanced unresectable esophageal cancer treated
      by chemoradiation therapy and S-1+CDDP chemotherapy].
AB  - We report a 37-year-old woman who complained of chest discomfort as of August
      2004, and was found to have advanced esophageal cancer in the upper thoracic area
      in December 2004.S he was diagnosed as Stage IVa (T4N1M0) because chest computed
      tomography (CT) indicated trachea invasion and lymph node metastasis. We
      diagnosed it to be a case of unresectable esophageal cancer, and she underwent
      chemoradiation therapy. CT showed regression of the main tumor and metastatic
      lymph nodes when the CRT course was completed. The main tumor disappeared
      macroscopically. We again considered an operation, but the CRT was so effective
      that the patient wished to continue CRT and underwent three courses. Endoscopy
      showed disappearance of the main tumor and Lugol's solution. Following this, 10
      courses of the treatment with CDDP alone (CDDP 10 mg/weekly) were continued until
      the appearance of renal dysfunction. S-1 (100 mg/body/day)was started in
      September 2005. The treatment is currently ongoing, and no recurrence or
      metastases had occurred as of March 2009.

PMID- 20154490
TI  - [A case showing a complete response by weekly paclitaxel associated with severe
      empyema and mediastinal abscess caused by reduction of a recurrent lung
      metastatic tumor originating from adenocarcinoma of the esophagogastric junction
      after primary operation].
AB  - The patient was a 57-year-old man who presented with cancer of the
      esophagogastric junction. He underwent total gastrectomy, lower esophagectomy,
      distal pancreatectomy and splenectomy with para-aortic lymphnode dissection by
      the transthoracoabdominal approach. He was given a daily dose of 100 mg of S-1 as
      adjuvant chemotherapy. About one year after the operation, lung metastasis was
      recognized by enhanced CT examination. He began weekly paclitaxel as second-line
      chemotherapy. Paclitaxel was infused once a week. About two weeks after the first
      infusion therapy, he was admitted to our hospital with fever and dyspnea. A chest
      enhanced CT revealed remarkable empyema and mediastinal abscess. Chest drainage
      and mediastinal drainage were performed.After one month of drainage, the empyema
      and mediastinal abscess had improved. The metastastic tumor of the lung
      disappeared at the time of discharge. CR has been maintained for more than a year
      without chemotherapy.This case suggests that remarkable reduction of the tumor
      induced by chemotherapy may have caused the empyema and mediastinal abscess.

PMID- 20154491
TI  - [Histological complete response in a case of primary squamous cell carcinoma of
      the stomach treated by chemotherapy with docetaxel and cisplatin plus 5
      fluorouracil].
AB  - The patient was a 68-year-old man with melena. Endoscopic examination revealed a
      type 2 advanced tumor in the mid body and an elevated lesion in the upper body of
      the stomach. Biopsy specimens from both lesions were diagnosed histologically as
      squamous cell carcinoma. Abdominal CT showed thickening of the midbody in the
      greater curvature and bulky lymph nodes along the lesser curvature (No. 3), and
      the greater curvature(No. 4d). We diagnosed Stage IIIB (cP0, cH0, cT4, cN1, cM0)
      cancer, but we concluded radical resection would be difficult due to lymph node
      invasion to the diaphragm and mesocolon. DCF combination therapy (docetaxel 75
      mg/m2 day 1, CDDP 75 mg/m2 day 1, 5-FU 750 mg/m2 day 1-5) was administered. After
      3 courses of chemotherapy, endoscopic examination and abdominal CT findings
      showed remarkable reduction of the primary tumor and the lymph node metastasis,
      indicating a partial response (PR) to the chemotherapy. After consultation with
      the patient, total gastrectomy with lymph node dissection (D2) was performed. The
      pathological specimens showed no cancer cells in the gastric wall and lymph
      nodes, so the histological effect was judged as Grade 3. This case suggested that
      DCF combination chemotherapy may prove useful to treat patients with advanced
      squamous cell carcinoma of the stomach.

PMID- 20154493
TI  - [A case of advanced gastric cancer responding to S-1 chemotherapy for three
      weeks].
AB  - We reported a patient with advanced gastric cancer successfully treated with S-1
      chemotherapy for three weeks. The patient was a 67-year-old man who had gastric
      cancer clinically diagnosed as cT3N1H0P0M0, stage IIIA. His treatment was
      supposed to be daily oral administration of 120 mg S-1 for 28 days. At 21 days,
      this treatment was stopped due to severe appetite loss. The histological
      diagnosis of the resected stomach revealed complete disappearance of cancer cells
      in the stomach and the regional lymph nodes. Our report suggested that S-1 may
      have a potent therapeutic effect in neoadjuvant chemotherapy for advanced gastric
      cancer.

PMID- 20154492
TI  - [A case of type 4 gastric cancer with peritoneal dissemination complicating
      venous thromboembolism treated effectively by combination of S-1 and warfarin].
AB  - A 49-year-old female patient was admitted to our hospital for a type 4 gastric
      cancer with peritoneal dissemination. Two courses of paclitaxel (PTX), and eight
      courses of S-1 were carried out. Although a partial response was obtained, she
      had complications with a deep venous thromboembolism (DVT) and pulmonary embolism
      (PE) during the treatment. Heparin, followed by warfarin, was useful to treat the
      embolism. After the venous thromboembolism (VTE) disappeared, combination therapy
      with S-1 and warfarin were started, and the quality of life (QOL) of this patient
      was maintained for about one year. Fine monitoring of the international
      normalized ratio (INR) was required in order to prevent side effects of blood
      coagulation by S-1 and warfarin coadministration. This case suggests that the
      combination therapy of S-1 and warfarin may be a safe and effective treatment
      able to prolong time to progression against a type 4 gastric cancer with VTE.

PMID- 20154494
TI  - [A case of early poorly-differentiated neuroendocrine carcinoma of stomach].
AB  - A 45-year-old male was admitted to our hospital complaining of anemia. Gastric
      endoscopy showed a type IIa+IIc tumor at the anterior wall of the gastric angle.
      Based on the pathology of the biopsy specimen, poorly-differentiated
      adenocarcinoma was diagnosed. Computed tomography scans showed regional lymph
      node swelling. Distal gastrectomy with a D2 lymph node dissection was performed.
      On pathology, the tumor was immunohistochemically positive for chromogranin A and
      synaptophysin. The Ki67 index was 70%. The tumor was diagnosed as poorly
      differentiated neuroendocrine carcinoma of the stomach. He was treated with S-1
      and CPT-11. Neuroendocrine cell carcinoma of the stomach is rare and usually has
      a very poor prognosis. Thus, we are reporting this case of early poorly
      differentiated neuroendocrine carcinoma of the stomach that was curatively
      resected and had 12-month survival without recurrence.

PMID- 20154495
TI  - [A case of advanced ascending colon cancer, curatively resected after complete
      response in left supraclavicular and paraaortic lymph nodes and liver metastases
      to FOLFOX4 therapy].
AB  - We report a resected case of ascending colon cancer with left supraclavicular and
      paraaortic lymph nodes and liver metastases which completely responded in terms
      of metastases but not the primary tumor to FOLFOX4 therapy. A 62-year-old woman
      with epigastric discomfort was initially diagnosed as malignant lymphoma by FDG
      PET with abnormal accumulation at left supraclavicular and paraaortic lesions.
      Pathological examination of the supraclavicular lymph nodes showed
      undifferentiated adenocarcinoma, and ascending colon cancer was detected by
      colonoscopy which was a mixture of various types of differentiation. FOLFOX4
      therapy was effective for metastatic lesions but colon tumor did not regress and
      was accompanied by abdominal pain. Macroscopically, a curative right
      hemicolectomy was performed, and microscopic examination revealed that the tumor
      had become a mass of undifferentiated cancer cells. Thus, the present case
      demonstrates the dedifferentiation of colon cancer during chemotherapy.

PMID- 20154496
TI  - [A case successfully treated with total pelvic exenteration after preoperative
      chemotherapy FOLFOX4 plus bevacizumab for unresectable sigmoid colon cancer with
      extramural progression].
AB  - The patient was a 73-year-old woman. Her chief complaints were abdominal pain and
      lower abdominal distension. After some examinations, we diagnosed pelvic tumor,
      bladder cancer (adenocarcinoma) and sigmoid colon cancer. We performed a first
      operation, but the pelvic tumor was firmly fixed anterior to the sacrum and right
      common pelvic artery. We judged it unresectable and performed tumor biopsy and
      ileostomy. The pathological findings were very similar to sigmoid colon cancer,
      so we diagnosed that the pelvic tumor was sigmoid colon cancer with extramural
      progression. Later, the patient was treated with three courses of FOLFOX4 and
      three courses of bevacizumab+FOLFOX4. After this chemotherapy, the pelvic tumor
      was reduced significantly, we considered resection possible and performed pelvic
      exenteration. She has had no recurrence for 6 months after second operation. This
      treatment appeared to be effective for unresectable primary colon cancer.

PMID- 20154497
TI  - [Multiple liver metastases due to sigmoid colon cancer successfully treated by
      degradable starch microspheres (DSM)-TAE, radiofrequency ablation therapy, and
      Uzel/UFT].
AB  - A69-year-old man was diagnosed with sigmoid colon cancer and underwent resection
      of the sigmoid colon. He was later diagnosed with multiple liver metastases 11
      months after resection of the sigmoid colon cancer. He was treated by
      intraarterial chemoembolization using degradable starch microspheres (DSM) and
      radiofrequency ablation therapy. As a systemic therapy, combined oral
      administration of tegafur/uracil (UFT) and Leucovorin(Uzel) was started (UFT 450
      mg/day, Leucovorin 75 mg/day, 4 weeks of therapy followed by a 1-week treatment
      break). Two months after 4 courses, the liver metastases had markedly diminished
      and CEA was within the normal range. The metastases had almost disappeared and
      tumor markers decreased to within normal limits. This treatment was very safe and
      effective. Such a strategic multidisciplinary treatment can lead to a better
      prognosis for colorectal cancer with liver metastases.

PMID- 20154498
TI  - [A case of complete response after treatment with UFT and leucovorin for
      synchronous multiple liver metastases of rectal cancer].
AB  - The patient was a 55-year-old female who had multiple liver metastases of rectal
      cancer. This patient underwent hepatic arterial infusion chemotherapy after low
      anterior resection for rectal cancer. Hepatic arterial infusion was discontinued
      due to severe diarrhea, and the administration of UFT (300 mg/day) and LV(75
      mg/day) was then begun. The carcinoembryonic antigen (CEA) level was normalized
      immediately after the start of this administration. One year later, liver
      metastases disappeared on computed tomography (CT) and a complete response (CR)
      was achieved. No adverse events were noted, and CR was maintained for 2 years.
      This therapy can serve as one of the chemotherapies for advanced colorectal
      cancer.

PMID- 20154499
TI  - [A case of multiple pulmonary and remnant liver metastases of hepatocellular
      carcinoma (HCC) after partial hepatic resection remarkably responding to S-1].
AB  - A 73-year-old woman was admitted to our hospital for hemorrhagic shock due to HCC
      rupture and treated by transcatheter arterial chemoembolization (TACE) in July
      2007, followed by partial hepatic resection two months later. Multiple pulmonary
      and remnant liver metastases were detected by CT six months after the surgery.
      Since treatment with UFT for two months was not effective, the chemotherapy was
      changed to S-1 100 mg/body/day in June 2008. After S-1 treatment for three
      months, lung metastases remarkably diminished, as did the serum AFP level.
      Meanwhile, although the S-1 dose was gradually reduced to 50 mg/body/day due to
      adverse effects, pulmonary lesions and serum AFP level remained stationary for
      five months. While there is no established regimen for distant metastases of HCC,
      S-1 may be effective even at a reduced dose.

PMID- 20154500
TI  - [Adult T-cell leukemia/lymphoma in a patient on hemodialysis-resistance to CHOP,
      but unexpected effect and remission achieved by sobuzoxane alone].
AB  - A 66-year-old man, on thrice-weekly hemodialysis for 7 years, was referred to
      Chiba Cancer Center Hospital in August 2006 because of a left axillary tumor.
      Computed tomography revealed several enlarged lymph nodes assembling at the left
      axilla. The serum soluble IL-2 receptor was 47,500 U/mL, and HTLV-1 antibody was
      positive. His parents came from Kyushu. The pathological diagnosis was peripheral
      T-cell lymphoma, CD4(+). He was clinically diagnosed as having an adult T-cell
      leukemia/lymphoma, lymphoma type, and clinical stage II. Two courses of CHOP
      therapy were given to the patient, without any response. Because the patient had
      to undergo hemodialysis consistently, we preferred mild salvage therapy to more
      intensive treatment. Then, sobuzoxane (SBZ), 1,600 mg/day in two divided doses,
      was administered orally for 5 days. Soon thereafter, unexpectedly, the axillary
      tumor rapidly became small, resulting in disappearance four months later. SBZ
      therapy, 800 mg/day x 3 days, was continued at intervals of 7 to 8 weeks until
      October 2008. At the time of reporting, May 2009, the patient was well without
      recurrence of ATLL, and the remission has lasted 26 months or more. The reason
      why CHOP-resistant ATLL responded dramatically to SBZ alone is not clear, but the
      plasma concentration of the metabolite of SBZ was possibly very high because of
      renal failure. Another possibility is that hemodialysis removed the growth
      factor(s) or anti-apoptotic factor(s) derived from ATLL cells.

PMID- 20154501
TI  - [Successful treatment with reduced-intensity stem cell transplantation for
      primary myelofibrosis].
AB  - A 60-year-old man was found to have anemia and leukocytosis from a health
      examination, and diagnosed with primary myelofibrosis (PMF). He was treated with
      low-dose melphalan but required frequent transfusions of red blood cells, and his
      splenomegaly enlarged. He received reduced-intensity stem cell transplantation
      (RIST)from an HLA-identical unrelated donor. The recovery of hematopoiesis was
      delayed due to the small number of transplanted cells (0.4 x 10(8)/kg).
      Splenomegaly and myelofibrosis gradually improved, and transfusion was not
      necessary 6 months later. He died of pneumonia about 1 year after
      transplantation. However, this case suggests that RIST is an effective treatment
      for PMF with giant splenomegaly.

PMID- 20154502
TI  - [Chemotherapy-naive advanced malignant fibrohistiocytoma presenting IVC syndrome
      case report].
AB  - The case was a 77-year-old male with swelling of his right leg. Physical
      examination revealed an ill-defined mass at RLQ. Computed tomography (CT) and 3
      dimensional CT showed an 8-cm tumor on the IVC, partially replacing iliac vessels
      and invading the psoas muscle. A diagnosis of malignant fibrohistiocytoma was
      made by pathological examination of biopsied specimens at exploratory laparotomy.
      Five courses of combination chemotherapy of ifosfamide (IFM) and doxorubicin
      (DXR) resulted in PR. Edema of the lower leg and hydronephrosis were both
      alleviated. Another 5 courses of chemotherapy with epirubicin and IFM were added.
      PR lasted 2 years, though the patient succumbed to the disease in 2 years and 8
      months.

PMID- 20154503
TI  - [The role of psychosomatic medicine doctors in palliative care medicine--two case
      reports].
AB  - Palliative care medicine deals with the issue of death by listening to the story
      of patient's lives. There are several problems such as stress overload or burnout
      due to the difficulty in responding to all demands from patients and the
      shortness of time. These problems sometimes make doctors specializing in
      palliative care have less interest in patients, negative feelings or an
      indifferent attitude to them. In this report, two cases in which a psychosomatic
      medical doctor intervened were analyzed. The satisfaction of patients and the
      stress overload of doctors engaged in palliative care were examined
      retrospectively by investigation of patients' charts. Both factors were improved
      by such interventions, thus underscoring the possible contributions by these
      doctors in cancer medicine. Psychosomatic medicine is based on a biopsychosocial
      model and related to both physical and psychosocial factors. There are many
      similar viewpoints between psychosomatic medicine and palliative care medicine.
      Psychosomatic medical doctors have an advantage in that they can contribute to
      palliative care without stress overload or burnout because of their special
      training in communication skills to deal with patients from the standpoints of
      both mind and body. However, these doctors have not received psychiatric training
      so as to be able to diagnose precisely and treat psychiatric problems such as
      adjustment disorders, depression and delirium. Therefore, their further training
      in psychiatry for several months or years is an issue to be addressed in future.

PMID- 20154504
TI  - [Efforts of pharmacists in regimen management for safe cancer chemotherapy].
AB  - As a safe way to manage cancer chemotherapy, a regimen registration system of
      chemotherapies was started in our hospital in April of 2007. Only chemotherapies
      registered in the regimen system can be conducted. Beginning in July of 2007, to
      assure safer chemotherapy, a standard clinical value of laboratory data was
      established as the criteria to discontinue chemotherapies. The individual
      laboratory data have been checked according to the discontinuance criteria by
      pharmacists in our hospital. With the adoption of this regimen registration
      system for standardized procedures of various chemotherapies, laboratory data can
      be checked according to the criteria, and certain chemotherapies can now be
      discontinued. However, in certain cases some doctors proceeded chemotherapies
      although pharmacists suggested that laboratory data did not meet the criteria. It
      is important to keep checking the registered regimen and criteria. Pharmacists
      have to confirm the checking system based on the patient's condition and improve
      the regimen system of chemotherapy more clearly together with doctors and nurses.

PMID- 20154505
TI  - Increased muscle strength improves managing in activities of daily living in fall
      prone community-dwelling older women.
AB  - BACKGROUND AND AIMS: The aim of this longitudinal study was to describe whether
      an increase in knee extension strength is associated with improvements in
      managing in activities of daily living (ADL) and in self-perceived physical
      condition in fall-prone community-dwelling older women. METHODS: Subjects (n=417)
      aged >= 65 years belonged either to intervention or control groups in a 12-month
      randomized controlled fall prevention trial. Isometric muscle strength of knee
      extension was measured with an adjustable dynamometer chair. Managing in
      activities of daily living was measured with structured questions about abilities
      to climb stairs, walk at least 400 meters, toilet, bath, go to the sauna, do
      light or heavy housework, and carry heavy loads. A question of self-perceived
      physical condition was also asked. RESULTS: Positive associations were found
      between increased knee extension strength and an increase in walking at least 400
      meters (p<0.001), carrying heavy loads (p=0.004), and climbing stairs (p=0.007),
      and in self perceived physical condition (p=0.005) over a 12- month follow-up. In
      addition, low age, non-use of a walking aid, low number of prescribed
      medications, and good functional balance at baseline were associated with an
      increase in performance of these ADL functions. CONCLUSIONS: An increase in knee
      extension strength during the 12-month follow-up was associated with improvement
      in some ADL functions and improvement in self-perceived physical condition during
      the same period in fall-prone community-dwelling women.

PMID- 20154506
TI  - Silver paper: the future of health promotion and preventive actions, basic
      research, and clinical aspects of age-related disease.

PMID- 20154507
TI  - Silver paper: the future of health promotion and preventive actions, basic
      research, and clinical aspects of age-related disease--a report of the European
      Summit on Age-Related Disease.
AB  - BACKGROUND. In September 2008, under the French Presidency of the European Union
      and with the support of the Polish Minister of Health, a European Summit on Age
      Related Disease was organised inWroclaw (Poland). At this meeting, European
      politicians, gerontologists and geriatricians gathered to discuss a common
      approach to future challenges related to age-related disease. Politicians and
      decision-makers from the European Union and Ministers of Health and their
      deputies from many European countries raised the problems and difficulties to be
      tackled in a growing population with a high burden of disease, and asked
      scientists to write a consensus document with recommendations for future actions
      and decisions. Scientists and clinicians worked in parallel in three different
      groups, on health promotion and preventive actions, basic research in age-related
      disease, and clinical aspects of disease in older people. Beforehand, the format
      of the paper with recommendations was discussed, and it was finally agreed that,
      for a better understanding by decision- makers, it would be divided in two
      different columns: one with facts that were considered settled and agreed by most
      experts (under the heading We know), and a second with recommendations related to
      each fact (We recommend). No limit on the number of topics to be discussed was
      settled. After careful and detailed discussion in each group, which in most cases
      included the exact wording of each statement, chairpersons presented the results
      in a plenary session, and new input from all participants was received, until
      each of the statements and recommendations were accepted by a large majority.
      Areas with no consensus were excluded from the document. Immediately after the
      Summit, the chairpersons sent the document both to the main authors and to a list
      of experts (see footnote) who had made presentations at the summit and agreed to
      review and critically comment on the final document, which is presented below. As
      regards the scientific aspects of the planning of the Summit, several
      organisations, under the leadership of the EUGMS, were asked both to review the
      program and to suggest names of speakers and participants. After the Summit, the
      Boards of these organizations (European Union Geriatric Medicine Society (EUGMS),
      International Association of Gerontology and Geriatrics-European Region (IAGGER),
      European Association of Geriatric Psychiatry (EAGP), International Society of
      Gerontechnology (ISG) and International Society for the Study of the Aging Male
      (ISSAM) agreed to consider the document as an official paper, and help with its
      dissemination. The name Silver Paper was used, recalling the grey or silvery hair
      of our older citizens, as an easy reference. It has been sent officially to
      several bodies of the European Union and to Health Ministers of most European
      countries; and will be published in other languages in local journals. Its
      declared intention is to foster changes in policies which may, in the future,
      reduce the burden of disease in old age.

PMID- 20154508
TI  - Beyond the neurotransmitter-focused approach in treating Alzheimer's disease:
      drugs targeting beta-amyloid and tau protein.
AB  - Drugs currently used to treat Alzheimer's Disease (AD) have limited therapeutic
      value and do not affect the main neuropathological hallmarks of the disease,
      i.e., senile plaques and neurofibrillar tangles. Senile plaques are mainly formed
      of beta-amyloid (Abeta), a 42-aminoacid peptide. Neurofibrillar tangles are
      composed of paired helical filaments of hyperphosphorylated tau protein. New,
      potentially disease-modifying, therapeutic approaches are targeting Abeta and tau
      protein. Drugs directed against Abeta include active and passive immunization,
      that have been found to accelerate Abeta clearance from the brain. The most
      developmentally advanced monoclonal antibody directly targeting Abeta is
      bapineuzumab, now being studied in a large Phase III clinical trial. Compounds
      that interfere with proteases regulating Abeta formation from amyloid precursor
      protein (APP) are also actively pursued. The discovery of inhibitors of beta
      secretase, the enzyme that regulates the first step of the amyloidogenic
      metabolism of APP, has been revealed to be particularly difficult due to inherent
      medicinal chemistry problems, and only one compound (CTS-21166) has reached
      clinical testing. Conversely, several compounds that inhibit gamma-secretase, the
      pivotal enzyme that generates Abeta, have been identified, the most advanced
      being LY-450139 (semagacestat), now in Phase III clinical development. Compounds
      that stimulate alpha-secretase, the enzyme responsible for the non-amyloidogenic
      metabolism of APP, are also being developed, and one of them, EHT-0202, has
      recently entered Phase II testing. Potent inhibitors of Abeta aggregation have
      also been identified, and one of such compounds, PBT-2, has provided encouraging
      neuropsychological results in a recently completed Phase II study. Therapeutic
      approaches directed against tau protein include inhibitors of glycogen synthase
      kinase- 3 (GSK-3), the enzyme responsible for tau phosphorylation and tau protein
      aggregation inhibitors. NP-12, a promising GSK-3 inhibitor, is being tested in a
      Phase II study, and methylthioninium chloride, a tau protein aggregation
      inhibitor, has given initial encouraging results in a 50-week study. With all
      these approaches on their way, the hope for disease-modifying therapy in this
      devastating disease may become a reality in the next 5 years.

PMID- 20154509
TI  - Medical treatment of osteoporosis in the elderly.
AB  - Fractures, mostly of the hip and pelvis, wrist, and sometimes of the vertebra,
      account for nearly half of emergency department treatments for elderly
      individuals seen because of a fall. Bone density measurements show that more than
      half of these patients have osteoporosis. The notion that it is too late to start
      treatment in a late stage of the disease forms a barrier to treatment. The aim of
      this article is to evaluate the effectiveness of therapeutic options for
      osteoporosis in the elderly, with a view to reducing the incidence of fractures.
      Although most studies of fracture reduction with medical treatment were not
      designed for the "geriatric" population, the average age of participants in most
      clinical trials was about 70 years. Nowadays, clinicians can choose from several
      effective treatments for the prevention of osteoporotic fractures in high-risk
      postmenopausal women. Data on the antifracture potential of calcium/vitamin D,
      raloxifene, bisphosphonates, strontium ralenate, and parathyroid hormone are now
      available. In all major studies patients also received calcium and vitamin D
      supplements. Bisphosphonates and strontium ranelate are good choices for first-
      or second-line treatment, while for the time being parathyroid hormone should
      only be used for the second-line treatment of osteoporosis in the elderly. The
      ease of use of bisphosphonates, with once weekly, once monthly, or intravenous
      administration, may be advantageous for elderly patients already taking multiple
      medications.

PMID- 20154510
TI  - A novel model of integrated care for the elderly: COPA, Coordination of
      Professional Care for the Elderly.
AB  - Despite strong evidence for the efficacy of integrated systems, securing the
      participation of health professionals, particularly primary care physicians
      (PCPs), has proven difficult. Novel approaches are needed to resolve these
      problems. We developed a model - COPA - that is based on scientific evidence and
      an original design process in which health professionals, including PCPs, and
      managers participated actively. COPA targets very frail community-dwelling elders
      recruited through their PCP. It was designed to provide a better fit between the
      services provided and the needs of the elderly in order to reduce excess
      healthcare use, including unnecessary emergency room (ER) visits and
      hospitalizations, and prevent inappropriate long-term nursing home placements.
      The model's originality lies in: 1) having reinforced the role played by the PCP,
      which includes patient recruitment and care plan development; 2) having
      integrated health professionals into a multidisciplinary primary care team that
      includes case managers who collaborate closely with the PCP to perform a
      geriatric assessment (InterRAI MDS-HC) and implement care management programs;
      and 3) having integrated primary medical care and specialized care by introducing
      geriatricians into the community to see patients in their homes and organize
      direct hospitalizations while maintaining the PCP responsibility for medical
      decisions. Since COPA is currently the subject of both a quasi-experimental study
      and a qualitative study, we are also providing preliminary findings. These
      findings suggest that the model is feasible and well accepted by PCPs and
      patients. Moreover, our results indicate that the level of service utilization in
      COPA was less than what is reported at the national level, without any
      compromises in quality of care.

PMID- 20154511
TI  - Serum lipids and their association with mortality in the elderly: a prospective
      cohort study.
AB  - BACKGROUND AND AIMS: To determine whether high levels of serum total cholesterol
      and low levels of high-density lipoprotein cholesterol (HDLc) are associated with
      increased mortality in the elderly. METHODS: Prospective cohort study of 1032 non
      institutionalized people aged 70 in the city of Turku, Southern Finland. The
      cohort population was recruited as part of a larger longitudinal aging study, the
      Turku Elderly Study. Fasting serum levels of total cholesterol, HDL-c and
      triglycerides were measured, and the amount of low-density lipoprotein
      cholesterol was calculated at baseline. The cohort was followed for mortality for
      12 years, and the causes of death were recorded and further classified into
      cardiovascular and other causes of death. The hazard ratios of dying for subjects
      in various cholesterol quartiles were computed by the Cox proportional hazards
      model, adjusting for cardiovascular risk factors and pre-existing medical
      conditions. RESULTS: Low levels of serum total cholesterol and HDL-c were
      associated with a greater risk of death over a follow-up of 12 years. After
      adjustment for several cardiovascular risk factors, the association between total
      cholesterol and survival changed. All-cause mortality seemed to be highest in the
      highest quartile of total cholesterol and nearly as high in the lowest quartile
      of total cholesterol, suggesting a U-shaped connection, but the differences were
      not statistically significant. However, cardiovascular mortality was
      significantly lowest in the lowest quartile of total cholesterol and
      significantly highest in the lowest quartile of HDL-c. CONCLUSIONS: High levels
      of serum total cholesterol and particularly low levels of HDL-c seem to be risk
      factors for cardiovascular mortality even in the elderly population.

PMID- 20154512
TI  - Asymptomatic carotid plaque and pro-inflammatory genetic profile in the elderly.
AB  - BACKGROUND AND AIMS: Several indices of subclinical atherosclerosis (ATS),
      including ultrasound (US) scan of carotid vessels, have received attention in
      clinical studies of the general population. Since inflammation takes part in the
      development of ATS, we studied the relationship between US imaging of carotid
      vessels and genetic predisposition to inflammation, in both elderly subjects
      without acknowledged CV risk factors and elderly subjects with acknowledged CV
      risk factors undergoing primary prevention. METHODS: Seventy-two elderly subjects
      (aged between 65-84) were divided into three groups on the basis of
      cardiovascular (CV) risk (G0: 0-9%, G1: 10-20% and G2: >20%) according to the
      NCEP Adult Panel III Report. They underwent US evaluation of carotid arteries and
      were analyzed for single nucleotide polymorphisms in the genes of a number of
      cytokines: TNF-alpha, TGF-beta1, IL-10, IL-6 and IFN-gamma. RESULTS: Asymptomatic
      carotid plaque (ACP) was detected in 19 subjects, not only in those belonging to
      the major risk group (36.8%) but also in those at lower risk (63.2%). In these
      subjects, we found a different genotype distribution in the polymorphisms of IFN
      gamma (+874), IL-6 (-174) and IL- 10 (-1082). The TT +874 IFN-gamma and GG -174
      IL-6 high producer-genotypes and the AA IL-10 low producergenotype were indeed
      more frequent in the ACP group (IFN-gamma: p=0.000 and IL-6: p=0.004). We found
      no correlation between genotype and carotid intima-media thickening. CONCLUSIONS:
      Our data suggest that, in the elderly, inflammation-associated polymorphisms are
      related to atherogenesis and that the finding of ACP on US scan can be valuable
      in identifying subjects at risk for CV events, even if they lack traditional
      cardiovascular risk factors such as an increase in IMT.

PMID- 20154513
TI  - Validation of lower extremity performance tests for determining the mobility
      limitation levels in community-dwelling older women.
AB  - BACKGROUND AND AIMS: Assessment of mobility status among community-dwelling older
      people is important for preventing further deterioration of mobility and
      identifying changes in mobility as early as possible. We attempted to identify
      the optimal cut-off values for eight lower extremity performance (LEP) tests in
      community-dwelling older women with mobility limitation (ML) levels. METHODS: The
      ML levels of 433 community-dwelling older women, mean age 73.2 years (SD 5.7,
      range 65-93) were classified according to selfreports. ML levels were identified
      by face-to-face interviews and according to self-reported difficulty in walking
      one-quarter of a mile or climbing 10 steps without resting. The LEP tests
      comprised one-legged stance, tandem stance, functional reach, tandem walk,
      alternate step, five chair sit-to-stands, timed up-and-go (TUG) and usual gait
      speed. Receiver-operating characteristic curves were obtained for all scales to
      assess optimal cut-off values. RESULTS: The optimal cut-off value of 6.52 (s) for
      the TUG test was shown by the highest sensitivity (74%) and specificity (71%) in
      the discrimination of no ML from moderate ML, whereas the optimal cut-off value
      of 1.05 (m/s) in the usual gait speed test showed the highest sensitivity (73%)
      and specificity (67%) in the discrimination of moderate ML from severe ML.
      CONCLUSIONS: Among community-dwelling older women, TUG and usual gait speed had
      the highest sensitivity and specificity in discriminating ML levels.

PMID- 20154515
TI  - Risk factors of functional decline during hospitalization in the oldest old.
AB  - BACKGROUND AND AIMS: The number of hospital admissions of the elderly is
      increasing and hospitalization often leads to functional decline. The aim of this
      study was to identify major risk factors for functional decline in the
      hospitalized oldest old. METHODS: Prospective, observational, non-randomized
      study of patients aged >/=80 years, admitted for at least two days to the
      University Department of Geriatric Medicine of Torino, Italy, between November
      2003 and November 2004. For detection of functional decline, the ADL scale was
      used, referring to the number of dependent ADL. RESULTS: At discharge, ADL mean
      scores were significantly higher than on admission (2.5+/-2 vs 2.3+/-1.9,
      p<0.001). 23.9% of the sample lost at least one ADL function during
      hospitalization, and 19.2% were transferred to long-term care, compared with 5.4%
      of those with no functional decline. Length of hospitalization, neoplasm, low
      level of albumin and high number of drugs prescribed were associated with
      functional decline. At multivariate analysis, only in-hospital stay was an
      independent risk factor for functional decline (RR 1.1 per day of
      hospitalization, CI 1.03-1.14). CONCLUSIONS: Hospitalization of the oldest old
      increases the risk of functional decline, especially if prolonged. It is
      important to identify patients at high risk for functional decline after hospital
      admission.

PMID- 20154514
TI  - Short Physical Performance Battery in hospitalized older adults.
AB  - BACKGROUND AND AIMS: The objectives of this study were to determine if Short
      Physical Performance Battery (SPPB) information could be collected in a
      hospitalized older patient population, and to assess associations between SPPB
      scores and sociodemographic characteristics and clinical measures. METHODS: A
      cross sectional design was used that included 90 adults aged 65 years or older
      admitted to an Acute Care for Elders unit. Patient information was collected
      within 24 hours of hospitalization. SPPB was scored using established criteria in
      older persons living in the community and revised criteria based on older persons
      hospitalized with acute illness. RESULTS: The mean age was 75.3 (SD 7.1) years;
      61% were women. The SPPB can be safely and reliably administered to hospitalized
      elderly patients. No injuries or adverse events occurred. Hospital SPPB scoring
      criteria better distributed the overall range of performance for older patients
      than community SPPB scoring criteria. In multivariate regression analyses,
      increasing age (p=0.007), length of stay (p=0.02), comorbidities (p=0.04), and
      cognition (p=0.02) were significantly and inversely associated with SPPB when
      scored using hospital based scoring criteria. Only age (p=0.02) was significantly
      associated with SPPB when using community based scoring criteria. CONCLUSIONS:
      This study showed that a SPPB can be reliably collected in hospitalized older
      patients. The study further suggests that hospital based SPPB scoring criteria
      may be more appropriate for an older patient population.

PMID- 20154516
TI  - Functional limitations of upper limbs in older diabetic individuals. The Italian
      Longitudinal Study on Aging.
AB  - BACKGROUND AND AIMS: This study aimed at assessing the prevalence rate of
      symptoms of shoulder osteoarthritis in diabetic subjects and their possible
      associations, as part of the prospective study called ILSA (Italian Longitudinal
      Study on Aging). METHODS: The study examined 5632 individuals aged 65-84 years,
      living either independently or in institutions. Of the above number, 2109
      subjects were examined in the 1996 follow-up, with evaluation of the diabetic
      status and osteoarthritis symptoms (at least one of the following sites: hand,
      knee, shoulder, hip). Associations between diabetes and osteoarthritis symptoms
      were examined by means of the chi2 test or the non-parametric Wilcoxon rank-sum
      test. Relationships of diagnoses of osteoarthritis and possible risk factors were
      analysed by multinomial logistic regression, adjusting for significant
      interactions. RESULTS: Only for shoulders did osteoarthritis symptoms reveal a
      significant association with diabetes (p=0.0107). Significant risk factors for
      shoulder osteoarthritis were gender, age, completed years of schooling, BMI and
      diabetes. A woman of </=76 years was 3.3 times more likely to have definite
      osteoarthritis and almost 2 times more likely to have possible osteoarthritis
      than a man of similar age. A man of over 76 years was estimated to be 3.5 times
      as likely to have definite osteoarthritis and almost 1.6 times more likely to
      have possible osteoarthritis than a younger man. CONCLUSIONS: It was concluded
      that the high prevalence rates of osteoarthritis symptoms in diabetic patients
      should be a major concern when planning treatment, because they might lead to a
      reduction in physical exercise, due to joint pain. Common pathophysiological
      pathways should be identified, such as RANKL/OPG and inflammation markers, to
      explain the independent association of these disabling conditions.

PMID- 20154517
TI  - Racial differences in gait mechanics associated with knee osteoarthritis.
AB  - BACKGROUND AND AIMS: This study examines racial differences in gait mechanics in
      persons with knee osteoarthritis and the influence of anthropometrics,
      educational level, radiographic disease severity (rOA), and self-report measures
      of pain and disability on racial differences in gait. METHODS: One hundred
      seventy five (64 black and 111 white) adults with radiographic knee OA were
      tested. 3-D kinematic and kinetic data were collected while subjects walked at
      two self-selected speeds (normal and fast). Anthropometric data, radiographic
      level of OA, and self-report measures of pain and disability were also collected.
      Gait patterns were compared across groups and within groups. RESULTS: Black and
      white subjects did not differ significantly in radiographic OA. However, blacks
      walked significantly more slowly when asked to walk fast. At the normal speed,
      blacks had a smaller knee range of motion and loading rate than whites. Blacks
      also took longer to reach their peak maximum ground reaction force than whites.
      Within black subjects variations in gait mechanics were primarily explained by
      BMI, rOA, selfreported psychological disability, and pain self-efficacy. In white
      subjects, variations in gait mechanics were primarily explained by weight, age,
      velocity, psychological disability, and self-efficacy. CONCLUSIONS: Blacks in
      this study had a pattern of gait mechanics generally associated with high levels
      of osteoarthritis, though they did not differ significantly in rOA from whites.
      The variability in gait patterns exhibited by blacks was most strongly related to
      variance in walking speed, anthropometrics, and perceived physical ability. Taken
      together, these results suggest that race is an important factor that must be
      considered in the treatment and study of osteoarthritis.

PMID- 20154518
TI  - Particularities of suicide in the elderly. A population-based study.
AB  - BACKGROUND AND AIMS: Suicide in later life stages is of growing concern as the
      life expectancy of Western populations is rising. Therefore, a population- based
      study concerning elderly suicide was undertaken. METHODS: The study included 1008
      suicides in Middle Franconia (Bavaria/Germany) between 2004 and 2007. Data was
      analyzed regarding gender, method chosen, initiating motive and chronobiological
      factors at the time of death. RESULTS: Higher rates of suicides were observed in
      the population at risk over 65 years old, in both sexes (age-adjusted suicide
      rate per 100,000 inhabitants for men: 42.52; 95% CI 8.64- 37.47; for women: 8.64;
      95% CI 6.81-10.96). There were significant differences regarding the method
      chosen (chi2=21.3; df=6; p=0.002) and the underlying motive, "mental/physical
      illness", was the predominant stressor (chi2=73.0; df=6; p<0.001). CONCLUSIONS:
      Suicide in the elderly population differs significantly from that in younger
      people. Understanding of this phenomenon must be further elucidated, since
      suicide is difficult to prevent, and its risk is expected to increase still
      further among the elderly.

PMID- 20154519
TI  - Cancrum oris in developed countries.
AB  - Cancrum oris (or noma) is a rapidly progressive disease characterized by
      destructive necrosis of oral tissues and underlying bone. It is part of a
      multistage condition and may represent the outcome of untreated necrotizing
      stomatitis. Necrotising stomatitis and cancrum oris predominantly affect children
      in developing countries, especially in Africa. Only few cases have been reported
      in developed countries, and were associated with debilitating diseases and
      disorders of the immune system. We report a case of noma in an elderly
      immunosuppressed Italian patient in whom necrosis caused an external buccal
      communication. This case stresses the importance of an early identification and
      prompt management of the necrotic condition, in order to avoid diffusion of the
      destructive process within the oro-facial tissues.

PMID- 20154520
TI  - Applying Dixon and Dixon's Integrative Model for Environmental Health Research
      toward a critical analysis of childhood lead poisoning in Canada.
AB  - Occurrences of childhood lead poisoning resulting from exposure to residential
      sources of lead is an underresearched area in Canada. Dixon and Dixon's
      Integrative Model for Environmental Health Research substantiates this claim by
      grouping Canadian research on this health topic into the model's 4 domains:
      physiological, vulnerability, epistemological, and health protection. This
      process is useful not only for identifying research gaps within the Canadian
      context but also in setting the groundwork for a future critical analysis to
      illuminate the sociopolitical and economic influences that shape healthcare
      knowledge, and ultimately, influence how healthcare providers and policy makers
      produce and use this information.

PMID- 20154521
TI  - A critical lens on the instrumentation of caring in nursing theory.
AB  - Critical Social Theory (CST) is a methodology that enables the researcher to
      examine the pressures and constraints in any society, posing the following
      questions: What is the false consciousness, the gaps and the silences as well as
      restraining, historical and mindlessly accepted norms. This CST lens is applied
      to Sumner's theory The Moral Construct of Caring in Nursing as Communicative
      Action and its instrumentation. The pilot testing data are discussed using
      Fontana's CST process: critique, context, politics, emancipatory intent,
      democratic structures, dialectic analysis, and reflexivity. Ideal communication
      in the nurse-patient relationship is bidirectional, multifaceted, complex, and
      difficult to achieve.

PMID- 20154522
TI  - The role of nursing in the rehabilitation of stroke survivors: an extended
      theoretical account.
AB  - This article provides a critique and theoretical extension of a work that sought
      to describe the contribution of nurses to stroke rehabilitation. At the time, the
      role of nursing was considered important but therapeutically nonspecific. Stroke
      nursing research has increased significantly and so has research focusing on the
      patient experiences of the adjustment and rehabilitation processes following a
      stroke. These developments provide significant new insights that may refine and
      extend the original understanding of the role of nursing in stroke
      rehabilitation. This article proposes an extended theoretical framework of the
      role of nursing in stroke recovery and rehabilitation.

PMID- 20154523
TI  - The stewardship model: current viability for genetic biobank practice
      development.
AB  - The "stewardship model" of ethics relationships is a conceptual framework
      initially proposed by Jeffers in Advances in Nursing Science, 24(2), 2001. It
      conceptualized ethical responsibilities in the practice of systematic collection
      and storage of biospecimens in biobanks for future healthcare genetic research.
      Since the article's publication 8 years ago, genetic biobanks have grown in
      number around the world and discernible biobank relational conceptualizations
      were published. Nursing leadership adopted competency standards for all genetic
      nursing practices. The involvement of nurses has increased and is projected for
      further significant increase as biobank practices emerge from research into
      clinical care settings. This assessment of current viability of this previously
      established stewardship model offers fresh insights to existing and future
      nursing research and practice. The purpose of this article was to analyze the
      original stewardship model's components, the relational parties, and
      characteristics; by contrasting those with proposed conceptualizations and
      existing biobank practices developed subsequent to its publication. The model's
      current viability and theoretical development status are assessed for its ability
      to support a future nursing evidence base for best practices. Proposals for the
      model's expansion are suggested.

PMID- 20154524
TI  - Passionate scholarship 2001-2010: a vision for making academe safer for joyous
      risk-takers.
AB  - What is passionate scholarship? According to students and graduates from a
      nursing doctoral program interviewed 10 years ago, passionate scholars must risk
      committing to a personally meaningful and socially relevant topic close to the
      heart. This insight spawned a string of exploratory inquiries and educational
      interventions in search of the "ideal conditions" that foster passionate
      scholarship. Updating the findings of that original study published in Advances
      in Nursing Science in 2001, this article describes a 3-year, faculty development
      initiative. Beyond increasing scholarly productivity, the findings suggest that
      turning faculty groups into communities of scholarly caring can make academic
      environments safer for passionate risk-takers.

PMID- 20154526
TI  - "Web-based weight management programs for children and adolescents: a systematic
      review of randomized controlled trial studies" by An, Hayman, Park, Dusaj, and
      Ayres (July-September 2009, Vol 32, No 3, pp 222-240).

PMID- 20154527
TI  - Unitary appreciative inquiry: evolution and refinement.
AB  - Unitary appreciative inquiry (UAI), developed over the past 20 years, provides an
      orientation and process for uncovering human wholeness and discovering life
      patterning in individuals and groups. Refinements and a description of studies
      using UAI are presented. Assumptions and conceptual underpinnings of the method
      distinguishing its contributions from other methods are reported. Data generation
      strategies that capture human wholeness and elucidate life patterning are
      proposed. Data synopsis as an alternative to analysis is clarified and
      explicated. Standards that suggest enhancing the legitimacy of knowledge and
      credibility of research are specified. Potential expansions of UAI offer
      possibilities for extending epistemologies, aesthetic integration, and theory
      development.

PMID- 20154528
TI  - Hegemony, hermeneutics, and the heuristic of hope.
AB  - Hope has become a commodity, one that society expects those who suffer to invest
      in and one that healthcare providers are expected to promote as an outcome. In
      nursing research, a single hegemonic epistemology/ontology has been implemented
      through an exclusive hermeneutic (interpretation of data) and has resulted in
      hope being designated as an external objective heuristic for those who suffer.
      Evidence is articulated in this article for adopting a broader method of analysis
      and interpretation (genealogy) that can facilitate fuller apprehension of hope in
      the human experience of suffering and despair.

PMID- 20154529
TI  - Acquired factor VIII hemophilia in a trauma patient: case report and literature
      review.

PMID- 20154530
TI  - Pancreatic duct transection: diagnosis and management.

PMID- 20154531
TI  - Nonoperative management of the child with severe pancreatic and splenic injury:
      should this become our preferred approach?

PMID- 20154532
TI  - Colostomy-sparing fecal diversion in a child after extensive perianal trauma.

PMID- 20154533
TI  - Fat embolism may be responsible for hypoxemia in trauma patients with no
      radiological pulmonary abnormalities.

PMID- 20154534
TI  - Trifurcated radial nerve in the spiral groove of the humerus.
AB  - A 62-year-old man presented with a nonunion of the humerus shaft. Using a
      standard triceps splitting approach, a longitudinal incision along the posterior
      aspect of the arm was created. Three independent radial nerves coursed
      posteriorly and inferolaterally around the humerus were identified in spiral
      groove. Three nerves resembled in the size, color, and course in the operative
      field. Although the prevalence of the anomaly is probably quite low, the
      possibility of identification of this anomalous condition of radial nerve should
      be kept in mind when performing posterior approach on the humerus.

PMID- 20154535
TI  - The Trauma Quality Improvement Program: pilot study and initial demonstration of
      feasibility.
AB  - OBJECTIVE: The American College of Surgeons Committee on Trauma has created a
      "Trauma Quality Improvement Program" (TQIP) that uses the existing infrastructure
      of Committee on Trauma programs. As the first step toward full implementation of
      TQIP, a pilot study was conducted in 23 American College of Surgeons verified or
      state designated Level I and II trauma centers. This study details the
      feasibility and acceptance of TQIP among the participating centers. METHODS: Data
      from the National Trauma Data Bank for patients admitted to pilot study hospitals
      during 2007 were used (15,801 patients). A multivariable logistic regression
      model was developed to estimate risk-adjusted mortality in aggregate and on three
      prespecified subgroups (1: blunt multisystem, 2: penetrating truncal, and 3:
      blunt single-system injury). Benchmark reports were developed with each center's
      risk adjusted mortality (expressed as an observed-to-expected [O/E] mortality
      ratio and 90% confidence interval [CI]) and crude complication rates available
      for comparison. Reports were deidentified with only the recipient having access
      to their performance relative to their peers. Feedback from individual centers
      regarding the utility of the reports was collected by survey. RESULTS: Overall
      crude mortality was 7.7% and in cohorts 1 to 3 was 16.4%, 12.4%, and 5.1%,
      respectively. In the aggregate risk-adjusted analysis, three trauma centers were
      low outliers (O/E and 90% CI <1) and two centers were high outliers (O/E and 90%
      CI >1) with the remaining 18 centers demonstrating average mortality. Challenges
      identified were in benchmarking mortality after penetrating injury due to small
      sample size and in the limited capture of complications. Ninety-two percent of
      survey respondents found the report clear and understandable, and 90% thought
      that the report was useful. Sixty-three percent of respondents will be taking
      action based on the report. CONCLUSIONS: Using the National Trauma Data Bank
      infrastructure to provide risk-adjusted benchmarking of trauma center mortality
      is feasible and perceived as useful. There are differences in O/E ratios across
      similarly verified or designated centers. Substantial work is required to allow
      for morbidity benchmarking.

PMID- 20154536
TI  - Injury severity and quality of life: whose perspective is important?
AB  - BACKGROUND: Ambiguity exists regarding factors that predict postinjury quality of
      life (QOL). We hypothesized that patient-perceived injury severity, not Injury
      Severity Score (ISS), would be correlated with QOL in a model that included
      severity of post-traumatic stress disorder (PTSD) symptoms. METHODS: Four hundred
      twenty-six trauma patients admitted to a Level I trauma center completed a
      questionnaire during inpatient stay and 6 months after injury. The questionnaire
      assessed physical component score and mental component score QOL with the SF-36,
      PTSD severity using the PTSD checklist, and used a four-point rating of perceived
      injury severity. ISS and demographic information were obtained from the trauma
      registry. Statistical analysis was done with Pearson's correlation and multiple
      regressions. RESULTS: ISS was not significantly correlated with perceived injury
      severity, PTSD symptom severity, physical component score, or mental component
      score. The majority of patients overestimated injury severity when compared with
      ISS. An increase in PTSD symptom severity and perceived injury severity
      significantly predicted both decreased physical and mental QOL at 6 months.
      CONCLUSIONS: ISS does not give the full picture of the severity of injury.
      Surgeons should consider early screening of patients for perception of injury
      severity and PTSD symptoms to determine which patients may need psychologic
      intervention to improve long-term QOL.

PMID- 20154537
TI  - Safety evaluation of new hemostatic agents, smectite granules, and kaolin-coated
      gauze in a vascular injury wound model in swine.
AB  - BACKGROUND: In 2007, a potent procoagulant mineral called WoundStat (WS),
      consisting of smectite granules, received clearance from the Food and Drug
      Administration for marketing in the United States for temporary treatment of
      external hemorrhage. Previously, we found that microscopic WS particles remained
      in the injured vessels that were treated, despite seemingly adequate wound
      debridement. Thus, we investigated the thromboembolic risk of using WS when
      compared with kaolin-coated gauze, Combat Gauze (CG); or regular gauze, Kerlix
      (KX) to treat an external wound with vascular injuries in pigs. METHODS: The
      right common carotid artery and external jugular vein of pigs were isolated and
      sharply transected (50%). After 30 seconds of free bleeding, the neck wounds were
      packed with WS, CG, or KX and compressed until hemostasis was achieved (n = 8 per
      group). Wounds were debrided after 2 hours, and vascular injuries were primarily
      repaired with suture. Blood flow was restored after infusing 1 L of crystalloid
      (no heparin or aspirin) and the wounds were closed. Two hours later, computed
      tomographic angiography was performed, and the wounds were reopened to harvest
      the vessels. The brains and lungs were recovered for gross and microscopic
      examination after euthanasia. RESULTS: No differences were found in baseline
      measurements. Thrombelastography showed similar hypercoagulability of the final
      blood samples when compared with baselines in all groups. All vessels treated
      with KX or CG were patent and had no thrombus or blood clot in their lumen. In
      contrast, seven of eight carotid arteries and six of eight jugular veins treated
      with WS developed large occlusive red thrombi and had no flow. Small clots and WS
      residues were also found in the lungs of two pigs. Histologically, significant
      endothelial and transmural damage was seen in WS-treated vessels with luminal
      thrombi and embedded WS residues. CONCLUSION: WS granules caused endothelial
      injury and significant transmural damage to the vessels that render them
      nonviable for primary surgical repair. The granules can enter systemic
      circulation and cause distal thrombosis in vital organs. More relevant in vitro
      and in vivo safety tests should be required for clearance of new hemostatic
      agents.

PMID- 20154538
TI  - Intestinal mucus layer preservation in female rats attenuates gut injury after
      trauma-hemorrhagic shock.
AB  - BACKGROUND: We tested the hypothesis that females are more resistant to trauma
      hemorrhagic shock (T/HS)-induced gut injury than males, and this is related to
      better preservation of their intestinal mucus layer, which is influenced in turn
      by the estrus cycle stage at the time of injury. METHODS: Male, proestrus and
      diestrus female rats underwent a laparotomy (trauma) and 90 minutes of shock (
      approximately 35 mm Hg). At 3 hours after reperfusion, terminal ileum was
      harvested and stained with Carnoy's Alcian Blue for mucus assessment, hematoxylin
      and eosin, and periodic acid schiff for villous and goblet cell morphology and
      injury. Ileal permeability was measured in separate intestinal segments using the
      ex vivo everted gut sac technique. RESULTS: When compared with males, proestrus
      female rats were significantly more resistant to T/HS-induced morphologic gut
      injury, as reflected in both a lower incidence of villous injury (14% vs. 22%; p
      < 0.05) and a lesser grade of injury (1.0 vs. 2.8; p < 0.05) as well as
      preservation of gut barrier function (17.9 vs. 32.2; p < 0.05). This resistance
      to gut injury was associated with significant preservation of the mucus layer
      (87% vs. 62%; p < 0.05) and was influenced by the estrus cycle stage of the
      female rats. There was a significant inverse correlation between mucus layer
      coverage and the incidence (r = 0.9; p < 0.0001) and magnitude (r = 0.89; p <
      0.0001) of villous injury and gut permeability (r = 0.74; p < 0.001).
      CONCLUSIONS: The resistance of female rats to T/HS-induced intestinal injury and
      dysfunction was associated with better preservation of the intestinal mucus
      barrier and was to some extent estrus cycle-dependent. Preservation of the mucus
      barrier may protect against shock-induced gut injury and subsequent distant organ
      injury by limiting the ability of luminal contents such as bacteria and digestive
      enzymes from coming into direct contact with the epithelium.

PMID- 20154539
TI  - A hospital-based violence prevention tour: a collaborative approach to empower
      youth.
AB  - BACKGROUND: Youth violence is a significant problem in the United States with
      high recidivism rates. Considering these high recidivism rates in youths after an
      initial injury, we hypothesized a hospital-based violence prevention program
      aimed at increasing awareness, empowering positive conflict resolution, and
      promoting future vocational goals would benefit at-risk youth before they are
      injured. METHODS: A feasibility study was completed on our Violence and Injury
      Prevention (VIP) tour program at our urban Level I trauma center. Participants
      were at-risk youth, aged 11 years to 17 years. Anonymous data were collected
      using an Audience Response System. RESULTS: One hundred eighty-five students
      participated from January 2007 to August 2008. Sixty-three percent were 6th to
      8th graders, 70% were boys. Seventy-nine percent stated that they knew someone
      who had been injured or killed because of violence, with significantly more boys
      than girls (p = 0.05). More boys than girls stated that they have access to a gun
      (p < 0.05). Almost 60% of the participants stated that they had engaged in
      violence within the past 6 months, with no difference by gender (p = 0.085). Of
      the respondents, 84.2% reported an increase in their awareness on the
      consequences of violence. This was more significant for girls than boys (p <
      0.05). Of the participants, 86.3% reported increased understanding of hospital
      care for a trauma patient. Participants stated that they would recommend VIP to
      others. CONCLUSION: VIP educated local urban youth about violence and increased
      their awareness of the injuries resulting from violence. In addition, at-risk
      youths were exposed to career opportunities in health care.

PMID- 20154540
TI  - Contrast-induced nephropathy in elderly trauma patients.
AB  - BACKGROUND: Computed tomography (CT) is the gold standard for the identification
      of occult injuries, but the intravenous (IV) contrast used in CT scans is
      potentially nephrotoxic. Because elderly patients have decreased renal function
      secondary to aging and chronic disease, we sought to determine the rate of acute
      kidney injury (AKI) in elderly trauma patients exposed to IV contrast. METHODS:
      Medical records of patients older than 55 years evaluated at a level-one trauma
      center between January 2003 and July 2008 were reviewed. Contrast was nonionic,
      isosmolar, and administered in standard volumes. Groups were based on
      administration of contrast. AKI was defined as a 25% relative or 0.5 mg/dL
      absolute increase in serum creatinine within 72 hours of presentation
      [corrected]. RESULTS: During the study period 1,371 patients older than 55 years
      were evaluated, and 1,152 met the inclusion criteria. CT was performed on 1,071
      patients (96%); 71% of this group received IV contrast. There was no significant
      difference between the contrast and noncontrast groups in terms of baseline
      characteristics. Criteria for AKI were satisfied in 2.1% of all patients,
      including 1.9% the contrast group versus 2.4% in the noncontrast group. AKI
      diagnosed within 72 hours of patient presentation was an independent risk factor
      for in-hospital mortality and prolonged length of stay. CONCLUSIONS: IV contrast
      media in elderly trauma patients is not associated with an increased risk of AKI.
      Development of AKI within 72 hours of admission is associated with mortality and
      increased length of stay.

PMID- 20154541
TI  - Early predictors of massive transfusion in patients sustaining torso gunshot
      wounds in a civilian level I trauma center.
AB  - BACKGROUND: Early prediction of the need for massive transfusion (MT) remains
      difficult. We hypothesized that MT protocol (MTP) utilization would improve by
      identifying markers for MT (>10 units packed red blood cell [PRBC] in 24 hours)
      in torso gunshot wounds (GSW) requiring early transfusion and operation. METHODS:
      Data from all MTPs were collected prospectively from February 1, 2007, to January
      31, 2009. Demographic, transfusion, anatomic, and operative data were analyzed
      for MT predictors. RESULTS: Of the 216 MTP activations, 78 (36%) patients
      sustained torso GSW requiring early transfusion and operation. Five were moribund
      and died before receiving MT. Of 73 early survivors, 56 received MT (76%, mean 19
      units PRBC) and 17 had early bleeding control (EBC), (24%, mean 5 units PRBC).
      Twelve transpelvic and 13 multicavitary wounds all received MT regardless of
      initial hemodynamic status (mean systolic blood pressure: 96 mm Hg; range, 50
      169). Of 31 MT patients with low-risk trajectories (LRT), 18 (58%) had a systolic
      blood pressure <90 mm Hg compared with 3 of 17 (17%) in the EBC group (p < 0.01).
      In these same groups, a base deficit of <-10 was present in 27 of 31 (92%) MT
      patients versus 4 of 17 (23%) EBC patients (p < 0.01). The presence of both
      markers identified 97% of patients with LRT who requiring MT and their absence
      would have potentially eliminated 16 of 17 EBC patients from MTP activation.
      CONCLUSIONS: In patients requiring early operation and transfusion after torso
      GSW: (1) early initiation of MTP is reasonable for transpelvic and multicavitary
      trajectories regardless of initial hemodynamic status as multiple or difficult to
      control bleeding sources are likely and (2) early initiation of MTP in patients
      with LRT may be guided by a combination of hypotension and acidosis, indicating
      massive blood loss.

PMID- 20154543
TI  - Improved survival time with combined early blood transfusion and fluid
      administration in uncontrolled hemorrhagic shock in rats.
AB  - OBJECTIVE: To test whether early blood administration combined with crystalloid
      solution infusion may prolong survival in a clinically relevant model of ongoing
      uncontrolled life-threatening hemorrhage. METHODS: Light anesthesia was induced
      with halothane in 24 rats, and spontaneous breathing was maintained. Uncontrolled
      hemorrhagic shock was induced by withdrawal of blood at 2.5 mL/100 g over a 15
      minute period, followed by 75% tail amputation. At 10 minutes after tail cutting,
      rats were randomized into four groups (n = 6 each): group 1, receiving 3 mL of
      shed blood for 5 minutes followed by 9 mL of lactated Ringer's (LR) solution for
      15 minutes; group 2, receiving 9 mL of LR solution for 15 minutes followed by 3
      mL of shed blood for 5 minutes; group 3, receiving 9 mL of LR solution only for
      15 minutes; group 4, receiving neither of shed blood nor LR solution. Rats were
      then observed until death or a maximum of 180 minutes. RESULT: Mean survival time
      was 138 +/- 30 minutes, 108 +/- 22 minutes, 79 +/- 13 minutes, and 55 +/- 18
      minutes for groups 1, 2, 3, and 4, respectively (p < 0.05 among the four groups).
      Additional blood loss from the tail stump did not differ significantly between
      the three treatment groups. CONCLUSIONS: In a model of uncontrolled hemorrhagic
      shock in rats, a resuscitation regimen using crystalloids agent alone is not
      ideal, and even a brief delay in blood administration worsens survival. Early
      blood administration combined with crystalloid solution infusion seems ideal.

PMID- 20154542
TI  - Resuscitation with fresh whole blood ameliorates the inflammatory response after
      hemorrhagic shock.
AB  - BACKGROUND: Hemorrhagic shock is the leading cause of potentially preventable
      death after traumatic injury. Hemorrhage and subsequent resuscitation may result
      in a dysfunctional systemic inflammatory response and multisystem organ failure,
      leading to delayed mortality. Clinical evidence supports improved survival and
      reduced morbidity when fresh blood products are used as resuscitation strategies.
      We hypothesized that the transfusion of fresh whole blood (FWB) attenuates
      systemic inflammation and reduces organ injury when compared with conventional
      crystalloid resuscitation after hemorrhagic shock. METHODS: Male mice underwent
      femoral artery cannulation and hemorrhage to a systolic blood pressure of 25 mm
      Hg +/- 5 mm Hg. After 60 minutes, the mice were resuscitated with either FWB or
      lactated Ringer's solution (LR). Mice were decannulated and killed at intervals
      for tissue histology, serum cytokine analysis, and vascular permeability studies.
      Separate groups of mice were followed for survival studies. RESULTS: When
      compared with FWB, mice resuscitated with LR required increased resuscitation
      fluid volume to reach goal systolic blood pressure. When compared with sham or
      FWB-resuscitated mice, LR resuscitation resulted in increased serum cytokine
      levels of macrophage inflammatory protein-1alpha, interleukin-6, interleukin-10,
      macrophage-derived chemokine, KC, and granulocyte macrophage colony stimulating
      factor as well as increased lung injury and pulmonary capillary permeability. No
      survival differences were seen between animals resuscitated with LR or FWB.
      CONCLUSIONS: Resuscitation with LR results in increased systemic inflammation,
      vascular permeability, and lung injury after hemorrhagic shock. Resuscitation
      with FWB attenuates the inflammation and lung injury seen with crystalloid
      resuscitation. These findings suggest that resuscitation strategies using fresh
      blood products potentially reduce systemic inflammation and organ injury after
      hemorrhagic shock.

PMID- 20154544
TI  - Traditional resuscitative practices fail to resolve metabolic acidosis in
      morbidly obese patients after severe blunt trauma.
AB  - BACKGROUND: Obesity is a risk factor for postinjury complications; in particular,
      obese patients develop multiple organ failure (MOF) at a greater rate than do
      normal weight counterparts. Evaluation of differences in resuscitative practices
      altered by body mass index (BMI) might provide an explanation for the increased
      risk of MOF seen in these high-risk patients. METHODS: We used prospectively
      collected multicenter data to retrospectively compare patients grouped by BMI
      with regard to resuscitation volumes and traditional end points during the first
      48 hours after injury. Marshall MOF score was used as the primary outcome
      measure. RESULTS: One thousand sixty-six patients were analyzed, with 877 meeting
      inclusion and exclusion criteria. All patients received similar volumes of
      resuscitation per kilogram lean and ideal body weight. Morbidly obese patients
      attained greater central venous pressures but otherwise differed little in
      attainment of standard cardiovascular end points. Despite this, morbidly obese
      patients resolved base deficit more slowly and remained in metabolic acidosis for
      48 hours postinjury. Morbidly obese patients with persistent metabolic acidosis
      developed MOF at a significantly greater rate than did normal weight patients
      with or without persistent metabolic acidosis. CONCLUSIONS: Morbidly obese trauma
      patients show prolonged metabolic acidosis despite receiving similar volumes and
      attaining similar end points of resuscitation when compared with patients in
      other BMI groups. Inadequate resuscitation based on inaccurate end points and
      metabolic disturbances associated with increased BMI are likely responsible;
      identification of the etiology, sources, and consequences of this acidosis may
      provide further insight into the susceptibility of the morbidly obese patient to
      develop postinjury organ failure.

PMID- 20154545
TI  - Predicting change of hemoglobin after transfusion in hemodynamically stable
      anemic patients in emergency department.
AB  - BACKGROUND: To investigate factors associated with change of post-transfusion
      hemoglobin level, and to derive an equation that predicts post-transfusion
      changes in hemoglobin levels in hemodynamically stable anemic patients who
      visited emergency department. METHODS: A retrospective medical record review of
      patients who were hemodynamically stable and transfused with packed red blood
      cells was undertaken. Patients were randomly divided into two groups. One group
      (derivation group, 70% of total patients) was analyzed for factors associated
      with changes in post-transfusion hemoglobin levels, and linear regression
      analysis was performed to derive a prediction equation. The derived prediction
      equation was then externally validated with the other group (validation group,
      30% of total patients). RESULTS: A total of 196 patients were enrolled. The 137
      patients (70% of total patients) in the derivation group were analyzed for
      factors associated with changes in post-transfusion hemoglobin. Of those, body
      surface area and initial hemoglobin level were significantly correlated with
      changes in post-transfusion hemoglobin levels (p < 0.05). From these variables,
      linear regression analysis resulted in a prediction equation. The derived
      equation was validated externally with the 59 patients (30% of total patients) in
      the validation group and found to have an excellent correlation (r = 0.73,
      intraclass correlation = 0.84, p < 0.05). CONCLUSIONS: Post-transfusion
      hemoglobin level in hemodynamically stable adult patients was associated with
      initial hemoglobin levels and body surface area. These factors must be considered
      when transfusing hemodynamically stable adult patients with anemia.

PMID- 20154546
TI  - Severe hypoglycemia while on intensive insulin therapy is not an independent
      predictor of death after trauma.
AB  - BACKGROUND: Fear of the adverse effects of hypoglycemia has limited the
      widespread application of intensive insulin therapy (goal, 80-110 mg/dL) in the
      trauma population. We hypothesized that severe hypoglycemia (SH; <or=40 mg/dL)
      was not an independent predictor of mortality in the trauma population. METHODS:
      An analysis of critically ill trauma patients treated with intensive insulin
      therapy from November 2005 to May 2008 was performed. The primary outcomes of
      interest were any episode of SH (<40 mg/dL) and all-cause inhospital mortality.
      Multivariate logistic regression was used to estimate the independent
      relationship between hypoglycemia and death. RESULTS: : Fifty-seven thousand two
      hundred eighty-four data entries (1,824 patients) from the euglycemia protocol
      were analyzed (mortality = 16.0%). Median glucose was 119 mg/dL, with 43% of
      values between 80 mg/dL and 110 mg/dL, 81% between 80 mg/dL and 150 mg/dL, and
      0.3% <40 mg/dL. There were 126 severe hypoglycemic episodes in 111 patients (6.1%
      of the patients). Multivariate logistic regression revealed that SH was not
      independently associated with death after adjusting for other known risk factors
      (odds ratio, 1.244; 95% confidence interval, 0.853-1.816; p = 0.257). CONCLUSION:
      Hypoglycemia may be an unavoidable byproduct of tight glucose control with 6.1%
      of the patients experiencing a severe hypoglycemic event (<40 mg/dL).
      Hypoglycemia is not an independent predictor of death. Hypoglycemia is a
      statistical probability of time spent on protocol rather than an event leading to
      death. These data suggest that lower glucose ranges should be targeted in the
      trauma population without fear of hypoglycemia's adverse effect on mortality.

PMID- 20154547
TI  - Recombinant factor VIIa for the correction of coagulopathy before emergent
      craniotomy in blunt trauma patients.
AB  - BACKGROUND: Recombinant activated factor VII (rFVIIa) has been associated with
      decreased blood transfusion requirements in trauma patients. Clinical use has
      recently been extended to the treatment of coagulopathic patients with traumatic
      brain injury, and results have been encouraging. However, the cost and possible
      thromboembolic complications of rFVIIa have been considered barriers to its
      widespread use. We hypothesize that rFVIIa would provide an effective and cost
      efficient means of correcting coagulopathy in patients with traumatic brain
      injury undergoing emergent craniotomy. METHODS: We performed a 2-year (2005-2006)
      retrospective study of adult blunt trauma patients with traumatic brain injury
      who presented coagulopathic (international normalized ratio [INR] >1.3) and
      required emergent craniotomy. We compared patients who did (rFVIIa group) and did
      not (no-rFVIIa group) receive rFVIIa to correct coagulopathy before craniotomy.
      RESULTS: There were 14 rFVIIa patients and 14 no-rFVIIa patients. The rFVIIa
      patients were older (59 years vs. 41 years, p = 0.04), but there was no
      difference in male gender (79% vs. 79%, p = 0.68), injury severity score (29 vs.
      29, p = 1.0), or Glasgow Coma Scale score (10 vs. 7, p = 0.67). Although there
      was no difference in admission INR (2.6 vs. 1.9, p = 0.10), the rFVIIa group was
      more often taking preinjury coumadin (57% vs. 14%, p = 0.05). The rFVIIa group
      had a preoperative INR (1.2 +/- 0.4 vs. 1.4 +/- 0.2, p = 0.05), but there was no
      difference in the time from admission to craniotomy (135 minutes vs. 182 minutes,
      p = 0.51). The rFVIIa group received fewer units of packed red blood cells
      (PRBCs) and plasma during the perioperative period. In addition, the rVIIa group
      consumed fewer costs of PRBC ($756 per patient vs. $2,916 per patient, p < 0.001)
      and plasma ($369 per patient vs. $927 per patient, p = 0.001). The rFVIIa group
      still consumed fewer total costs of transfused blood products when cost of rFVIIa
      was included ($2,557 per patient vs. $4,110 per patient, p = 0.04). There were no
      thromboembolic complications in either group. CONCLUSIONS: rFVIIa provides a cost
      efficient option to effectively correct coagulopathy in patients with traumatic
      brain injury undergoing emergent craniotomy. In addition, the use of rFVIIa is
      associated with decreased transfusion of PRBC and plasma and decreased
      transfusion-related hospital costs in this population.

PMID- 20154548
TI  - In vivo effect of propranolol dose and timing on cerebral perfusion after
      traumatic brain injury.
AB  - BACKGROUND: In vivo models of traumatic brain injury (TBI) demonstrate increased
      cerebral perfusion, decreased cerebral hypoxia, reduced cerebral edema, and
      improved neurologic recovery with propranolol administration. The purpose of this
      study was to determine the effect of different propranolol doses and timing on
      cerebral perfusion in a murine TBI model. METHODS: Fifteen minutes after TBI,
      three groups of mice (four mice per group) were randomized to receive intravenous
      injections of placebo, 4 mg/kg propranolol, or 1 mg/kg propranolol. Two delayed
      treatment groups were randomized to receive placebo or 4 mg/kg propranolol 60
      minutes after TBI. Cerebral perfusion was then imaged by micropositron emission
      tomography. RESULTS: With placebo injection 15 minutes after TBI, the standard
      uptake value (SUV) mean was 0.395 +/- 0.01; with 4 mg/kg propranolol, the SUV
      mean was 0.515 +/- 0.04; and with 1 mg/kg propranolol, the SUV mean was 0.46 +/-
      0.01. Animals receiving 4 mg/kg propranolol demonstrated significant improvement
      (p < 0.01) in cerebral perfusion compared with placebo and compared with 1 mg/kg
      propranolol. With placebo injection at 60 minutes after TBI, the SUV mean was
      0.26 +/- 0.03; and with 4 mg/kg propranolol, the SUV mean was 0.43 +/- 0.02.
      After 60 minutes, animals receiving 4 mg/kg propranolol demonstrated significant
      improvement (p < 0.01) in cerebral perfusion compared with placebo. CONCLUSION:
      In a murine model of TBI, higher doses of propranolol were preferable to lower
      doses and both early and late propranolol administration improved cerebral
      perfusion. Potential mechanisms and therapeutic potential require further
      research.

PMID- 20154549
TI  - Isolated severe traumatic brain injuries: association of blood alcohol levels
      with the severity of injuries and outcomes.
AB  - BACKGROUND: Traumatic brain injury is a common cause of death after traumatic
      insults. Alcohol intoxication is a recognized contributor to the occurrence of
      these injuries. The specific effects of alcohol exposure on injury severity and
      subsequent outcomes, however, remain controversial. The aim of this study was to
      investigate the relationship between blood alcohol levels (BAL) and outcomes in
      patients with isolated severe traumatic brain injuries (sTBI). METHODS: During
      the calendar year 2003, as part of a pilot project, the Los Angeles County
      Department of Health Services obtained routine BAL on all patients transported to
      any of its 13 trauma centers. This study analyzes the effect of BAL on outcomes
      in patients with isolated sTBI (head Abbreviated Injury Scale (AIS) score >or=3;
      extracranial AIS score <3). The Low/No ethanol (ETOH) group included patients
      with negative or low (<0.08 mg/dL) BAL. Patients with BAL >or=0.08 mg/dL
      constituted the high ETOH group. Logistic regression was performed to determine
      whether alcohol levels had an independent association with outcomes. RESULTS:
      There were 815 patients with isolated severe head injuries. Overall, 468 patients
      (57%) constituted the Low/No ETOH group, and 347 (43%) the high ETOH group.
      Alcohol levels were not significantly associated with severity of injury,
      hypotension at admission, Glasgow Coma Scale score, incidence of major
      complications, and intensive care unit or hospital length of stay. However,
      adjusted mortality was significantly lower in the high ETOH group when compared
      with the Low/No ETOH (8.9% vs. 17.1%; adjusted odds ratio: 0.60, 95% confidence
      interval: 0.37-0.96, p = 0.037). In the subgroup of patients with Injury Severity
      Score >15 the relative risk for mortality in the high ETOH group was
      significantly lower than in patients with Low/No ETOH. There was also an
      increased survival with high ETOH in patients with Injury Severity Score >25, but
      this was not statistically significant. CONCLUSIONS: Among patients with isolated
      sTBI, BAL do not seem to be associated with overall injury severity, head injury
      severity, or the occurrence of major morbidities. Similarly, hospital and
      intensive care unit lengths are not affected by high admission BAL level. The
      adjusted overall in-hospital mortality, however, is significantly lower in
      patients presenting with the high BAL (>or=0.08 g/dL) after isolated sTBI.

PMID- 20154550
TI  - Early tracheostomy in intensive care unit: a retrospective study of 506 cases of
      video-guided Ciaglia Blue Rhino tracheostomies.
AB  - BACKGROUND: Percutaneous dilatational tracheostomy (PDT) is a common procedure in
      critically ill patients, but the correct timing is still controversial. This
      study was designed to establish whether an early timing in video-guided Ciaglia
      Blue Rhino PDT affects the duration of mechanical ventilation (MV) and the length
      of stay (LOS) in intensive care unit (ICU). Secondary clinical outcomes were the
      overall hospitalization duration and the mortality rate. METHODS: A
      retrospective, single-center study of 2,210 patients admitted to the ICU of the
      Emergency Department of the Careggi Teaching Hospital (Florence, Italy) between
      2002 and 2007. Among the 506 patients who underwent PDT, 256 and 250 patients
      were retrospectively assigned to the early tracheostomy (ET) or late tracheostomy
      (LT) group according to whether the procedure was performed before (ET) or after
      (LT) 3 days of MV (median time of procedure execution). RESULTS: The two groups
      of patients showed comparable demographic and clinical characteristics. The video
      guided PDT procedures were performed without major complications in all cases.
      The average timing of tracheostomy in the ET group was 1.9 +/- 0.9 days, whereas
      in LT group resulted 6.8 +/- 3.8 days (mean +/- SD). Total hospital LOS and
      mortality rate were not different between the two groups. However, the duration
      of MV days and of ICU LOS group were significantly shorter in the ET group (13.3
      +/- 9.6 and 16.9 +/- 13.0 days, respectively; p = 0.0001) than in the LT group
      (16.7 +/- 8.3 days and 20.8 +/- 9.2 days, respectively; p < 0.0001). Stratified
      analysis by the three major ICU admission diagnosis confirmed that both
      traumatized and nontraumatized (medical and postsurgical) ET patients had a
      shorter MV duration and ICU LOS as compared with LT patients. CONCLUSIONS: Video
      guided Ciaglia Blue Rhino PDT is safe and easy to perform in ICU. No difference
      in overall hospital LOS, incidence of pneumonia, and mortality rate between the
      ET and LT groups was found. However, in both traumatized and nontraumatized
      patients, shortened duration of ICU LOS and MV in the ET group (<or=3 days)
      indicates this procedure as a useful approach for patients and healthcare system.

PMID- 20154551
TI  - The clinical outcome of occult pulmonary contusion on multidetector-row computed
      tomography in blunt trauma patients.
AB  - BACKGROUND: Multidetector-row computed tomography (MDCT) is a more sensitive
      modality as compared with conventional radiography (CR) in detecting pulmonary
      injuries. MDCT often detects pulmonary contusion that is not visualized by CR,
      defined as occult pulmonary contusion (OPC). The aim of this study was to
      investigate whether OPC on MDCT has implications for the outcome in blunt trauma
      patients. METHODS: We used prospectively collected data from 1,040 adult high
      energy blunt trauma patients who were primarily presented at our emergency
      department and who underwent CR and MDCT of the chest. All patients with
      pulmonary contusion were identified and divided into two groups: The "CR/computed
      tomography (CT) group" consisted of patients with pulmonary contusion visible on
      both CR and MDCT. The "CT-only" group consisted of patients with OPC, visible
      exclusively on MDCT. The control group consisted of blunt trauma patients without
      pulmonary contusion. These groups were compared with respect to difference in
      mortality and other outcome measures. In addition, a multivariate analysis was
      performed. RESULTS: Two hundred fifty-five patients suffered pulmonary contusion:
      The CT-only group consisted of 157 and the CR/CT group of 98 patients. The CT
      only group did not differ from the control group with respect to mortality rate
      and other outcome measures. However, compared with the CR/CT group, mortality
      rate was significantly lower (8% versus 16%, p = 0.039) and most other outcome
      measures were significantly better in the CT-only group. CONCLUSION: OPC on MDCT
      is not associated with a worse outcome as compared with patients without
      pulmonary contusion. OPC has a better outcome as compared with pulmonary
      contusion visible on both CR and MDCT.

PMID- 20154552
TI  - Early onset pneumonia in severe chest trauma: a risk factor analysis.
AB  - BACKGROUND: The development of an early-onset pneumonia (EOP), occurring within
      the first 72 hours after admission, represents a critical event in severe
      thoracic trauma population. The aim of this study was to determine risk factors
      associated with the occurrence of this complication in this specific population.
      METHODS: A retrospective review of a prospective implemented trauma registry was
      conducted during a 4-year period in a Level I trauma center. Over the study
      period, 223 severely injured patients were admitted with severe thoracic trauma
      (Injury Severity Score >16 and Thorax Abbreviated Injury Score >2). Multiple
      logistic regression analysis was used to determine the independent predictors of
      EOP based on the clinical characteristics and the initial management both in the
      field and after admission in the trauma center. RESULTS: Independent predictors
      of EOP were the necessity of intubation and mechanical ventilation in the field
      (adjusted odds ratio [OR]: 11.8; 95% confidence interval [CI]: 4.3-32.7), a
      history of aspiration (OR: 28.6; 95% CI: 4.0-203.5), the presence of pulmonary
      contusion (OR: 7.0; 95% CI: 2.0-23.9), and the occurrence of a hemothorax (OR:
      3.2; 95% CI: 1.4-7.6). CONCLUSION: These results emphasize the influence of
      prehospital and early factors in the further occurrence of EOP, which allows the
      development of early and specific clinical management to prevent it.

PMID- 20154553
TI  - Anterior transposition of the superficial peroneal nerve branch during the
      internal fixation of the lateral malleolus.
AB  - BACKGROUND: Because of the anatomic variations of the superficial peroneal nerve
      (SPN), it has long been stressed that caution should be exercised at the time of
      open reduction and internal fixation (ORIF) of the lateral malleolus. METHODS:
      Blair and Botte described type B intermediate dorsal cutaneous nerve (IDCN) in
      which the SPN penetrates crural fascia posterior to the fibula about 5 cm
      proximal to the joint and crosses the lateral border of the fibulae. We
      hypothesized that the type B IDCN is especially vulnerable to direct surgical
      injury if present and the anterior transposition of this nerve may decrease the
      incidence of symptoms related to the SPN injury. Fifty-three ankle fractures in
      53 adult patients treated by the ORIF of lateral malleolus using the lateral
      approach between the periods from May 2001 to December 2006 were included.
      Intraoperative documentation about the presence of the type B IDCN variant at the
      surgical field was performed, and preoperative and postoperative sensory changes
      were carefully evaluated. RESULTS: We encountered Blair type B variant in 7 cases
      (12%). The IDCN was carefully dissected and transposed anteriorly before the
      plating. One of these seven patients had sensory deficit preoperatively, and it
      was recovered spontaneously 5 months after operation. There was one patient whose
      IDCN was inadvertently severed, and it was repaired. At the time of last follow
      up, only partial recovery of the sensory deficit was noted. Five of seven
      patients did not show any neurologic deficit with anterior transposition.
      CONCLUSION: Recognition and anterior transposition of the type B IDCN could
      reduce the incidence of the SPN nerve injuries during the ORIF of the lateral
      malleolar fractures.

PMID- 20154554
TI  - Use of homodigital reverse island flaps for distal digital reconstruction.
AB  - BACKGROUND: The homodigital reverse vascular island flap-a regional, axial
      patterned skin flap elevated with a vascular pedicle from the proximal digit-is a
      one-step procedure used to replace skin and soft tissue loss or destruction in
      the distal finger. The purpose of this study was to evaluate the clinical
      outcome. METHODS: From April 1993 to June 2005, 58 patients with a soft-tissue
      defect at the distal part of the finger were treated by homodigital island flaps
      for reconstruction. A "sensory" form island flap was used for defects in the
      pulps or fingertip, using reanastomosis of the terminal nerve end to the sensory
      nerve in the flap. We evaluated the active range of motion of the involved
      finger, hypersensitivity and cold intolerance, the patient's satisfaction with
      the appearance of the finger and the operation, and a two-point discrimination
      and pulp writing test, with at least 1 year of follow-up. RESULTS: Forty-five
      patients were followed up for at least 1 year after operation; 24 patients were
      treated with sensory-form reverse island flaps. The patients rarely complained of
      pain, anesthesia, or the cold intolerance of the flap. Both dynamic and static
      two-point discriminations were better in the sensory form than in the "arterial"
      form reverse vascular flap, with statistical difference. Seven patients aged
      older than 50 years were successfully treated and had a good functional outcome.
      CONCLUSIONS: The homodigital reverse island flap is an ideal surgical treatment
      for distal digital defects with a lower complication rate and good functional
      result, and the indication of age can be extended for older patients with a good
      preoperative evaluation.

PMID- 20154555
TI  - Effect of Astragalus membranaceus in rats on peripheral nerve regeneration: in
      vitro and in vivo studies.
AB  - BACKGROUND: This study provides in vitro and in vivo evaluation of Astragalus
      membranaceus (AM) on peripheral nerve regeneration. METHODS: In the in vitro
      study, we analyzed the effects of AM on cell differentiation and neurite
      outgrowth by using a PC12 cell model. In the in vivo study, silicone rubber
      chambers filled with the AM water extract were used to bridge a 10-mm sciatic
      nerve defect in rats. RESULTS: We found that the AM water extract caused a marked
      enhancement of the nerve growth factor-mediated neurite outgrowth and the
      expression of growth-associated protein 43 from PC12 cells. Animals from the
      groups treated with the AM for 8 weeks had a relatively more mature structure
      with larger mean values of myelinated axon number, endoneurial area, and total
      nerve area when compared with those in the controls receiving the saline only.
      CONCLUSION: These results suggest that the silicone rubber tubes present a good
      framework for the nerve fibers to regenerate across the gap, and the AM extract
      can be a potential nerve growth-promoting factor, being salutary in aiding the
      growth of axons in the peripheral nerve.

PMID- 20154556
TI  - Motorcycle-related injuries: effect of age on type and severity of injuries and
      mortality.
AB  - BACKGROUND: The aim of this study was to evaluate the relationship of age to the
      injury types, distribution, and severity in motorcycle crash (MCC) victims
      admitted to Los Angeles County emergency hospitals in California. METHODS: This
      Los Angeles countywide trauma registry study included all MCC victims admitted to
      the 13 trauma centers of the Los Angeles County between January 1995 and December
      2007. Besides demographical data collected, the Injury Severity Score, body area
      (head, chest, abdomen, and extremities), Abbreviated Injury Scale score >or=3,
      specific organ injuries, and mortality were calculated according to age groups
      (<or=18 years, 19-55 years, and >55 years). A stepwise logistic regression model
      was used to identify independent risk factors for death. RESULTS: Among 6,530
      admissions due to MCCs, there were 493 patients (7.5%) aged 18 years or younger,
      5,627 patients (86%) aged 19 years to 55 years, and 398 patients (6.5%) older
      than 55 years. The incidences of severe injury (Injury Severity Score >15) in the
      three ascending age groups were 23.5%, 30.3%, and 36.2%, respectively (p < 0.05),
      and critical injuries (Injury Severity Score >25) occurred in 6.5%, 12.3%, and
      13.8%, respectively (p < 0.05). Severe head injuries were significantly more
      likely in the population older than 55 year (odds ratio [OR] {95% confidence
      interval [CI] } = 1.45 {1.03-2.03}, p = 0.04). The risk of sustaining a severe
      chest injury (Abbreviated Injury Scale Chest Score >or=3) increased in a stepwise
      fashion with increasing age, with an OR (95% CI) = 1.86 (1.44-2.39) in the age
      group 19 years to 55 years and 2.81 (2.03-3.88) in the older than 55 years group,
      p < 0.001. Mortality was twofold higher in the 19-year- to 55-year-old group [OR
      (95% CI) = 2.30 (1.08-4.93), p = 0.03] and threefold higher in the older than 55
      years group [OR (95% CI) = 3.28 (1.36-7.93), p = 0.05] compared with the <or=18
      year-old group. CONCLUSIONS: Injuries related to MCCs show age-related injury
      distribution, severity, and mortality rates. Older patients are significantly
      more likely to suffer severe trauma, severe head and chest injuries, and spinal
      fractures. Adaptation of trauma team activation criteria and more aggressive
      triage of older victims of motorcycle trauma should be considered.

PMID- 20154557
TI  - Barriers to obtaining family consent for potential organ donors.
AB  - BACKGROUND: Our country suffers from a chronic shortage of organ donors, and the
      list of individuals in desperate need of life-saving organ transplants is growing
      every year. Family consent represents an important limiting factor for successful
      donation. We hypothesize that specific barriers to obtaining family consent can
      be identified and improved upon to increase organ donation consent rates. The
      purpose of this study was to compare families who declined organ donation to
      those who granted consent, specifically to identify barriers to family consent
      for successful organ donation. METHODS: We performed a 4-year (2004-2007)
      retrospective study of potential organ donors covered by our regional organ
      procurement organization (OPO). Variables collected included age, gender, race,
      cause of brain death (trauma vs. medical) of the potential organ donor, and
      elapsed time from declaration of brain death to family approach by OPO. Potential
      organ donors whose family declined organ donation (DECLINE group) were compared
      with potential organ donors whose family consented to organ donation (CONSENT
      group). Groups were compared using univariate and multivariate analysis. RESULTS:
      There were a total of 827 potential organ donors during the 4-year period within
      our OPO region. Overall, 471 families (57%) consented to organ donation, whereas
      356 families (43%) declined. Although there was no difference in male gender
      between the DECLINE and CONSENT groups (59% vs. 53%, p = 0.12), the DECLINE group
      had more medical brain deaths (73% vs. 58%, p < 0.001), more potential donors
      aged 50 years or older (43% vs. 34%, p < 0.001), as well as more potential organ
      donors of Hispanic (67% vs. 43%, p < 0.001) and African American (10% vs. 4%, p <
      0.001) descent. In addition, time from declaration of brain death to family
      approach by OPO was longer for the DECLINE group (350 minutes vs. 112 minutes, p
      = 0.001). Logistic regression identified race, older age, and death from a
      medical cause as independent risk factors for failure of obtaining consent.
      CONCLUSION: Several barriers exist to family consent for successful organ
      donation. Family members of minority populations, medical brain deaths, and older
      potential donors more often decline consent for organ donation. Family education
      and resource utilization toward these specific populations of potential organ
      donors may help to improve organ donation consent rates. In addition, delayed
      family approach by OPO seems to be associated with decreased consent rates.
      System improvements to expedite family approach by OPO may likewise lead to
      improved consent rates.

PMID- 20154560
TI  - Fixation of marginal posterior acetabular wall fractures using locking
      reconstruction plates and monocortical screws.
AB  - Marginal posterior wall fractures are often fixed by lag screws, which may be
      technically difficult and risks articular penetration. Spring plates are used to
      avoid articular penetration. Both lag screws and spring plates are usually
      buttressed by reconstruction plates. The aim of this report is to describe a
      technique for fixing those fractures using locking reconstruction plate and
      monocortical screws avoiding articular penetration and sparing spring plates. A
      locking reconstruction plate is placed in a position that allows buttressing of
      the fracture fragment and fixed proximally and distally first using non-locking
      screws. The marginal fracture is fixed using monocortical locking head screws.
      This technique has been performed on three patients; none had secondary
      displacement or nonunion. Fixing marginal posterior acetabular wall fractures
      using locking reconstruction plates and monocortical screws saves additional lag
      screws or spring plates without risking articular penetration.

PMID- 20154559
TI  - Blunt cerebrovascular injury practice management guidelines: the Eastern
      Association for the Surgery of Trauma.
AB  - BACKGROUND: Blunt injury to the carotid or vertebral vessels (blunt
      cerebrovascular injury [BCVI]) is diagnosed in approximately 1 of 1,000 (0.1%)
      patients hospitalized for trauma in the United States with the majority of these
      injuries diagnosed after the development of symptoms secondary to central nervous
      system ischemia, with a resultant neurologic morbidity of up to 80% and
      associated mortality of up to 40%. With screening, the incidence rises to 1% of
      all blunt trauma patients and as high as 2.7% in patients with an Injury Severity
      Score of >or=16. The Eastern Association for the Surgery of Trauma organization
      Practice Management Guidelines committee set out to develop an EBM guideline for
      the screening, diagnosis, and treatment of BCVI. METHODS: A computerized search
      of the National Library of Medicine/National Institute of Health, Medline
      database was performed using citations from 1965 to 2005 inclusive. Titles and
      abstracts were reviewed to determine relevance, and isolated case reports, small
      case series, editorials, letters to the editor, and review articles were
      eliminated. The bibliographies of the resulting full-text articles were searched
      for other relevant citations, and these were obtained as needed. These papers
      were reviewed based on the following questions: 1. What patients are of high
      enough risk, so that diagnostic evaluation should be pursued for the screening
      and diagnosis of BCVI? 2. What is the appropriate modality for the screening and
      diagnosis of BCVI? 3. How should BCVI be treated? 4. If indicated, for how long
      should antithrombotic therapy be administered? 5. How should one monitor the
      response to therapy? RESULTS: One hundred seventy-nine articles were selected for
      review, and of these, 68 met inclusion criteria and are excerpted in the attached
      evidentiary table and used to make recommendations. CONCLUSIONS: The East
      Practice Management Guidelines Committee suggests guidelines that should be safe
      and efficacious for the screening, diagnosis, and treatment of BCVI. Risk factors
      for screening are identified (see ), screening modalities are reviewed indicating
      that although angiography remains the gold standard, multi-planar (>or==8 slice)
      CT angiography may be equivalent, and treatment algorithms are evaluated. It is
      noted that change in the diagnosis and management of this injury constellation is
      rapid due to technological advancement and the difficulties inherent in
      performing randomized prospective trials in this patient population.

PMID- 20154561
TI  - Direct hip joint distraction during acetabular fracture surgery using the AO
      universal manipulator.
AB  - Certain acetabular fractures may necessitate distraction of the hip joint for
      removal of intra-articular debris and assessment of reduction. Distraction can be
      accomplished by manual traction, using a traction table or an AO universal
      manipulator (UM). The UM is a relatively simple and an inexpensive device that
      can provide focal distraction in a controlled manner without the risks associated
      with the use of a traction table. We describe a technique using the UM for hip
      joint distraction during acetabular fracture surgery through a Kocher-Langenbeck
      surgical exposure.

PMID- 20154562
TI  - Percutaneous 3 Kirschner wire fixation including the distal radioulnar joint for
      treatment of pilon fractures of the distal radius-technical note.

PMID- 20154563
TI  - Skin replacement in burn wounds.

PMID- 20154564
TI  - Retained intraocular nail with perforating injury of the eye.

PMID- 20154565
TI  - Diffuse retinal vasculitis in Citrobacter koseri traumatic endophthalmitis with
      intraocular foreign body.

PMID- 20154558
TI  - A critical assessment of the out-of-hospital trauma triage guidelines for
      physiologic abnormality.
AB  - BACKGROUND: It remains unclear whether the American College of Surgeons Committee
      on Trauma (ACSCOT) "step 1" field physiologic criteria could be further
      restricted without substantially sacrificing sensitivity. We assessed whether
      more restrictive physiologic criteria would improve the specificity of this
      triage step without missing high-risk patients. METHODS: We analyzed an out-of
      hospital, consecutive patient, prospective cohort of injured adults >or=15 years
      collected from December 1, 2005, to February 28, 2007, by 237 emergency medical
      service agencies transporting to 207 acute care hospitals in 11 sites across the
      United States and Canada. Patients were included based on ACSCOT field decision
      scheme physiologic criteria systolic blood pressure <or=90, respiratory rate <10
      or >29 breaths/min, Glasgow Coma Scale score <or=12, or field intubation. Seven
      field physiologic variables and four additional demographic and mechanism
      variables were included in the analysis. The composite outcome was mortality
      (field or in-hospital) or hospital length of stay >2 days. RESULTS: Of 7,127
      injured persons, 6,259 had complete outcome information and were included in the
      analysis. There were 3,631 (58.0%) persons with death or LOS >2 days. Using only
      physiologic measures, the derived rule included advanced airway intervention,
      shock index >1.4, Glasgow Coma Scale <11, and pulse oximetry <93%. Rule
      validation demonstrated sensitivity 72% (95% confidence interval: 70%-74%) and
      specificity 69% (95% confidence interval: 67%-72%). Inclusion of demographic and
      mechanism variables did not significantly improve performance measures.
      CONCLUSIONS: We were unable to omit or further restrict any ACSCOT step 1
      physiologic measures in a decision rule practical for field use without missing
      high-risk trauma patients.

PMID- 20154567
TI  - Head injury risk associated with feet-first free falls in 12-month-old children:
      a correlation of biomechanical study with human experience.

PMID- 20154568
TI  - Which drug for rapid sequence intubation?

PMID- 20154571
TI  - Computed tomographic angiography for blunt cerebrovascular injuries: is it good
      enough?

PMID- 20154569
TI  - The utility of focused assessment with sonography in trauma as a triage tool.

PMID- 20154572
TI  - Thrombelastography in trauma, the closer the better.

PMID- 20154576
TI  - The fate of newborn screening blood spots.

PMID- 20154577
TI  - Factors associated with delayed entry into primary HIV medical care after HIV
      diagnosis.
AB  - The aim of the study was to assess the median time between HIV diagnosis and
      entry into primary HIV medical care in a large urban area and to assess the
      potential individual, diagnosing facility, and community level factors
      influencing entry into care. One thousand two hundred and sixty-six individuals
      diagnosed with HIV in Philadelphia between 1 July 2005 and 30 June 2006 were
      followed until entry into care through 15 June 2007. Time to entry into care was
      calculated as a survival time variable and was defined as the time in months
      between the date of HIV diagnosis and the date more than 3 weeks after diagnosis
      when a CD4 cell count or percentage and/or HIV viral load were obtained. The
      median time to entry into care for all individuals was 8 months, with a range of
      1-26 months. Factors associated with delayed entry into care included age more
      than 40 years [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.75
      0.97] and diagnosis as an inpatient in the hospital (HR = 0.37; 95% CI = 0.37
      0.57). Factors associated with earlier entry into care included Hispanic
      ethnicity (HR = 1.39; 95% CI = 1.05-1.84), male sex with men as HIV transmission
      risk factor (HR = 1.27; 95% CI = 1.03-1.56), and residence in a census tract with
      a high poverty rate (HR = 1.68; 95% CI = 1.22-2.30). Individuals newly diagnosed
      with HIV in Philadelphia demonstrated marked delays in accessing care
      highlighting the tremendous need for interventions to improve overall linkage.
      These interventions should especially be targeted at those aged more than 40
      years and those diagnosed in the hospital.

PMID- 20154578
TI  - Raltegravir, maraviroc, etravirine: an effective protease inhibitor and
      nucleoside reverse transcriptase inhibitor-sparing regimen for salvage therapy in
      HIV-infected patients with triple-class experience.
AB  - We prospectively evaluated 28 triple-class experienced HIV-1-infected patients
      harbouring R5 virus, who received maraviroc, raltegravir and etravirine. By on
      treatment analysis, 26 (92%) had less than 50 copies HIV-RNA/ml at week 48. The
      median (interquartile range) 48-week increase in CD4 cell counts was 267 (136
      355) cells/microl. Three serious adverse events occurred: one recurrence of
      mycobacterial spondylodiscitis, one anal cancer, one Hodgkin lymphoma. Although
      long-term safety needs further study, this protease inhibitor and nucleoside
      analogue-sparing regimen showed sustained efficacy.

PMID- 20154579
TI  - Survival of HIV-infected patients with compensated liver cirrhosis.
AB  - INTRODUCTION: Since the advent of HAART, liver-related mortality has become the
      leading cause of non-AIDS deaths in HIV-infected patients in western countries,
      complications of end-stage liver disease due to chronic hepatitis B, chronic
      hepatitis C or both being mainly responsible. METHOD: The incidence and
      predictors of mortality were examined in HIV-infected patients with compensated
      liver cirrhosis. The accuracy of three different methods (elastometry, Child-Pugh
      and Model for End-Stage Liver Disease scores) to predict mortality was further
      examined. Cirrhosis was defined for hepatic elastometry values above 14.5 kPa.
      RESULTS: A total of 194 (11.4%) out of 1706 HIV-positive individuals were
      cirrhotic and were prospectively followed since October 2004 until December 2008.
      Overall, 89% of cirrhotic individuals had chronic hepatitis C, 10.3% chronic
      hepatitis B, 4.6% hepatitis delta and 4.1% liver disease of other causes or
      unknown cause. The overall mortality rate was 5.8 deaths per 100 patient-years.
      Multivariate analyses showed that age of at least 50 years (hazard ratio 4.76,
      95% confidence interval 1.66-13.59, P = 0.004), CD4 cell counts below 200
      cells/microl (hazard ratio 3.01, 95% confidence interval 1.26-7.23, P = 0.03) and
      detectable plasma HIV-RNA (hazard ratio 3.97, 95% CI, 1.53-10.27, P = 0.005) were
      associated with mortality. A baseline Model for End-stage Liver Disease score of
      at least 11 (P = 0.03) and hepatic elastometry values above 28.75 kPa (P = 0.001)
      were independent predictors of mortality. CONCLUSION: The death rate in HIV
      infected patients with compensated liver cirrhosis in the HAART era is 5.8%
      yearly, higher than mortality previously reported for either HIV-uninfected
      individuals with cirrhosis or noncirrhotic HIV-positive patients. Factors
      associated with mortality were older age, low CD4 cell counts and detectable
      plasma HIV-RNA. Both Model for End-Stage Liver Disease and especially hepatic
      elastometry accurately predicted mortality in this population.

PMID- 20154582
TI  - Novel histone deacetylase inhibitors CG05 and CG06 effectively reactivate
      latently infected HIV-1.
AB  - Histone deacetylase plays an important role in HIV latency. Novel histone
      deacetylase inhibitors, CG05 and CG06, were evaluated for their roles in HIV
      latency using ACH2 cells. Both inhibitors were highly efficient in reactivation
      of provirus and exerted lesser toxicity compared with other known histone
      deacetylase inhibitors. Histone acetylation increased when proviruses were
      reactivated by the compounds. These new inhibitors may contribute to the
      reduction of the HIV reservoir when used in conjunction with highly active
      antiretroviral therapy.

PMID- 20154580
TI  - Examining the promise of HIV elimination by 'test and treat' in hyperendemic
      settings.
AB  - BACKGROUND: It has been suggested that a new strategy for HIV prevention,
      'Universal Test and Treat', whereby everyone is tested for HIV once a year and
      treated immediately with antiretroviral therapy (ART) if they are infected, could
      'eliminate' the epidemic and reduce ART costs in the long term. METHODS: We
      investigated the impact of test-and-treat interventions under a variety of
      assumptions about the epidemic using a deterministic mathematical model. RESULTS:
      Our model shows that such an intervention can substantially reduce HIV
      transmission, but that impact depends crucially on the epidemiological context;
      in some situations, less aggressive interventions achieve the same results,
      whereas in others, the proposed intervention reduces HIV by much less. It follows
      that testing every year and treating immediately is not necessarily the most cost
      efficient strategy. We also show that a test-and-treat intervention that does not
      reach full implementation or coverage could, perversely, increase long-term ART
      costs. CONCLUSION: Interventions that prevent new infections through ART scale-up
      may hold substantial promise. However, as plans move forward, careful
      consideration should be given to the nature of the epidemic and the potential for
      perverse outcomes.

PMID- 20154583
TI  - Can the further clinical development of bevirimat be justified?

PMID- 20154584
TI  - Unusual body posture after death leading to signs of strangulation.
AB  - This report concerns a case in which the decedent was found in a highly unusual
      posture, one resembling a yoga backbend pose. Several findings in this case
      pointed to death by strangulation, including facial congestion, extensive
      petechiae of the conjunctivae and mucosal membranes of the oral cavity, and
      congestion and hemorrhaging in the lingual root, laryngopharynx, and cervical
      lymph nodes. However, no hemorrhaging of the cervical skin or soft tissue was
      observed. The cause of death was ultimately identified as pulmonary
      thromboembolism caused by an embolus originating from a deep leg vein thrombosis.
      If the pulmonary thromboembolism had not been detected, the cause of death may
      have been misidentified as strangulation.

PMID- 20154581
TI  - Plasma and cervical viral loads among Ugandan and Zimbabwean women during acute
      and early HIV-1 infection.
AB  - OBJECTIVES: High levels of HIV-1 viremia exist in peripheral blood during acute
      and early infection; however, data on HIV-1 viral loads in female genital
      secretions during this period are sparse. DESIGN: Prospective cohort of 188
      African women with primary HIV-1 infection. METHODS: HIV-uninfected and infected
      women were followed quarterly; we tested serial plasma specimens by HIV PCR to
      estimate infection dates. We used the Loess procedure to estimate the magnitude
      and timing of viral setpoints in plasma and cervical secretions and generalized
      estimating equations (GEE) to identify predictors of plasma and cervical viral
      setpoints. RESULTS: We estimated the mean HIV-1 plasma setpoint to be 4.20 log10
      HIV-1 RNA copies/ml [95% confidence interval (CI) 4.04-4.35] at 121 days (95% CI
      91-137) from infection; an analogous mean cervical viral setpoint was 1.64 log10
      HIV-1 RNA copies/swab (95% CI 1.46-1.82) at 174 days (95% CI 145-194) from
      infection. Cervical loads were significantly higher (0.7-1.1 log10 copies/swab)
      during acute infection than subsequently. Subtype D infection, pregnancy,
      breastfeeding, and older age at the time of infection were associated with higher
      plasma viral setpoint. Subtype C infection, nonviral sexually transmitted
      infections, having a partner spending nights away from home, recent unprotected
      sex, and shorter time since infection were associated with higher cervical HIV-1
      loads. Hormonal contraception was not associated with either the HIV-1 plasma
      setpoint or cervical loads during early infection. CONCLUSION: Cervical HIV-1
      viral loads were highest during acute infection and then declined up to 6 months
      following infection, when a 'setpoint' was attained. The prognostic value of a
      cervical 'setpoint' on future transmission risk remains unclear.

PMID- 20154585
TI  - A tissue microarray-based comparative analysis of novel and traditional
      immunohistochemical markers in the distinction between adrenal cortical lesions
      and pheochromocytoma.
AB  - We have encountered an increasing number of image-guided adrenal mass biopsies in
      which the differential diagnosis is adrenal cortical lesion versus
      pheochromocytoma. This distinction is sometimes difficult because of confounding
      clinical presentations, overlapping morphologies, and some degree of
      immunophenotypic overlap including focal staining with markers of purported
      lineage specificity. Interventional radiologists commonly use narrow gauge biopsy
      needles in this setting, which yield scant diagnostic tissue and further
      complicate pathologic evaluation. In this study, a detailed immunoprofile of 63
      adrenal cortical lesions (3 adrenal rests, 6 adrenal cortical hyperplasias, 43
      adrenal cortical adenomas, 4 adrenal cortical neoplasms of uncertain malignant
      potential, and 7 adrenal cortical carcinomas) was compared with 35
      pheochromocytomas using traditional (calretinin, chromogranin, inhibin, melanA,
      and synaptophysin) and novel [steroidogenic factor-1 (SF-1), microtubule
      associated protein 2, and mammalian achaete-scute homolog-1] antibodies, using
      tissue microarray technology to simulate small image-guided biopsies. Staining
      extent and intensity were each scored semiquantitatively for each antibody. A
      comparison of sensitivity and specificity using different intensity thresholds
      required for a "positive" result (> or = 1+ vs. > or = 2+) was performed.
      Staining results based on a > or = 1+ and (> or = 2+) intensity threshold were as
      follows: calretinin-95% (89%) in adrenal cortical lesions and 14% (0%) in
      pheochromocytomas; chromogranin-0% in adrenal cortical lesions and 100% in
      pheochromocytomas; inhibin-97% (86%) in adrenal cortical lesions and 6% (0%) in
      pheochromocytomas; microtubule-associated protein 2-29% (16%) in adrenal cortical
      lesions and 100% (89%) in pheochromocytomas; mammalian achaete-scute homolog-1-0%
      in both adrenal cortical lesions and pheochromocytomas; melanA-94% (86%) in
      adrenal cortical lesions and 6% (0%) in pheochromocytomas; SF-1-87% (86%) in
      adrenal cortical lesions and 0% in pheochromocytomas; synaptophysin-67% (59%) in
      adrenal cortical lesions and 100% in pheochromocytomas. Using an antibody panel
      consisting of chromogranin plus the nuclear antibody SF-1 and either calretinin
      or inhibin, while requiring a high-staining intensity threshold, helps to
      eliminate interpretative issues of artifactual or background reactivity, improves
      diagnostic sensitivity/specificity, and makes for an effective
      immunohistochemical approach in distinguishing adrenal cortical lesions from
      pheochromocytomas.

PMID- 20154586
TI  - EBV positive mucocutaneous ulcer--a study of 26 cases associated with various
      sources of immunosuppression.
AB  - We describe a series of Epstein Barr virus (EBV)-positive circumscribed,
      ulcerative lesions associated with various types of immunosuppression (IS). The
      study group (26 patients) comprised 10 males and 16 females, median age 77 years
      (range 42 to 101). IS in 9 cases included azathioprine (AZA), methotrexate (MTX)
      or cyclosporin-A (CyA). Seventeen patients had age-related immunosenescence.
      Patients presented with isolated sharply circumscribed ulcers involving
      oropharyngeal mucosa (16), skin (6), and gastrointestinal tract (4). Lesions were
      histologically characterized by a polymorphous infiltrate and atypical large B
      cell blasts often with Hodgkin/Reed-Sternberg (HRS) cell-like morphology. The B
      cells showed strong CD30 and EBER positivity, some with reduced CD20 expression,
      in a background of abundant T cells. CD15 was positive in 43% of cases (10/23).
      The pathologic features were identical regardless of the anatomic site or cause
      of IS. Polymerase chain reaction revealed 39% (7/18) clonal Ig gene
      rearrangements with 38% (6/16) and 31% (5/16) clonal and restricted T-cell
      patterns, respectively. Twenty-five percent of patients (5/20) received standard
      chemotherapy and/or radiotherapy. Forty-five percent (9/20) regressed
      spontaneously with no treatment and 15% (3/20) were characterized by a relapsing
      and remitting course. All of the iatrogenic lesions (6/6) with available follow
      up responded to reduction of IS. All patients achieved complete remission with no
      disease-associated deaths over a median follow-up period of 22 months (range 3 to
      72). We propose EBV-positive mucocutaneous ulcer as a newly recognized
      clinicopathologic entity with Hodgkin-like features and a self-limited, indolent
      course, generally responding well to conservative management. Association with
      various forms of IS implies a common pathogenetic mechanism. The localized nature
      of the disease may be owing to a minimal and localized lapse in
      immunosurveillance over EBV.

PMID- 20154587
TI  - The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying
      theory.
AB  - Ovarian cancer is the most lethal gynecologic malignancy. Efforts at early
      detection and new therapeutic approaches to reduce mortality have been largely
      unsuccessful, because the origin and pathogenesis of epithelial ovarian cancer
      are poorly understood. Despite numerous studies that have carefully scrutinized
      the ovaries for precursor lesions, none have been found. This has led to the
      proposal that ovarian cancer develops de novo. Studies have shown that epithelial
      ovarian cancer is not a single disease but is composed of a diverse group of
      tumors that can be classified based on distinctive morphologic and molecular
      genetic features. One group of tumors, designated type I, is composed of low
      grade serous, low-grade endometrioid, clear cell, mucinous and transitional
      (Brenner) carcinomas. These tumors generally behave in an indolent fashion, are
      confined to the ovary at presentation and, as a group, are relatively genetically
      stable. They lack mutations of TP53, but each histologic type exhibits a
      distinctive molecular genetic profile. Moreover, the carcinomas exhibit a shared
      lineage with the corresponding benign cystic neoplasm, often through an
      intermediate (borderline tumor) step, supporting the morphologic continuum of
      tumor progression. In contrast, another group of tumors, designated type II, is
      highly aggressive, evolves rapidly and almost always presents in advanced stage.
      Type II tumors include conventional high-grade serous carcinoma, undifferentiated
      carcinoma, and malignant mixed mesodermal tumors (carcinosarcoma). They
      displayTP53 mutations in over 80% of cases and rarely harbor the mutations that
      are found in the type I tumors. Recent studies have also provided cogent evidence
      that what have been traditionally thought to be primary ovarian tumors actually
      originate in other pelvic organs and involve the ovary secondarily. Thus, it has
      been proposed that serous tumors arise from the implantation of epithelium
      (benign or malignant) from the fallopian tube. Endometrioid and clear cell tumors
      have been associated with endometriosis that is regarded as the precursor of
      these tumors. As it is generally accepted that endometriosis develops from
      endometrial tissue by retrograde menstruation, it is reasonable to assume that
      the endometrium is the source of these ovarian neoplasms. Finally, preliminary
      data suggest that mucinous and transitional (Brenner) tumors arise from
      transitional-type epithelial nests at the tubal-mesothelial junction by a process
      of metaplasia. Appreciation of these new concepts will allow for a more rationale
      approach to screening, treatment, and prevention that potentially can have a
      significant impact on reducing the mortality of this devastating disease.

PMID- 20154589
TI  - Pitfalls in the use of smoothelin to identify muscularis propria invasion by
      urothelial carcinoma.
AB  - Studies predominantly performed on cystectomy specimens have shown that
      antibodies against smoothelin can distinguish between muscularis mucosae (MM)
      (negative or weak stain) and muscularis propria (MP) (strong stain). However,
      studies on diagnostically difficult (transurethral resection) specimens have not
      been performed. We studied 34 transurethral resection cases where outside
      pathologists questioned the presence of MP invasion. Upon expert review of the
      H&E slides, there was no MP invasion in 18 cases. Smoothelin in MM was negative
      in 8/18 (44%), weakly positive (1+) in 5/18 (28%), moderately positive (2+) in
      4/18 (22%), and moderately/strongly (2-3+) positive in 1/18 (6%). Smoothelin in
      uninvolved MP present in 8 cases was: 2+ in 2/8 (25%) and 3+in 6/8 (75%).
      Smoothelin expression in MM was weaker than in MP in 7/8 (88%) cases where both
      were present. Of 16 tumors with MP invasion, smoothelin in involved MP was: 1+ in
      1/16 (6%), 2+ in 3/16 (19%), 2 to 3+ in 9/16 (56%), and 3+ in 3/16 (19%).
      Smoothelin expression in concurrent uninvolved MP was similar. Our data confirm
      the relatively distinct staining pattern of smoothelin between MM and MP.
      However, due to the overlap of intensity between MM and MP, caution should be
      maintained while using smoothelin immunohistochemistry as a diagnostic tool for
      MP invasion.

PMID- 20154588
TI  - Pleomorphic ductal carcinoma of the breast: predictors of decreased overall
      survival.
AB  - The World Health Organization classification of tumors of the breast includes a
      rare variant of invasive ductal carcinoma termed pleomorphic carcinoma. This
      variant has marked nuclear pleomorphism (>6-fold variation in nuclear size by
      definition, but often>10-fold) and characteristically contains multinucleated
      tumor giant cells. Approximately one-third of the cases in the initial series
      contained a focal spindle cell metaplastic component. The tumors are reported to
      have an aggressive behavior, but because some contain a spindle cell metaplastic
      component, it is unclear whether the metaplastic component or other
      clinicopathologic features account for the poor clinical outcome. We identified
      37 cases of pleomorphic carcinoma of the breast and evaluated the association
      between clinical outcome and multiple clinicopathologic features. Patients with
      invasive pleomorphic lobular carcinoma and those without at least a tissue biopsy
      before chemotherapy were excluded. Patients ranged in age from 23 to 78 years
      (median, 49 y). Tumor size was >5 cm in 12 cases and <5 cm in 22. A focal spindle
      cell component (<25% of the tumor) was present in 14 tumors (38%). Clinical
      follow-up was available for 36 patients (median, 17 mo). In multivariate
      analysis, when the 2 stage-IV patients were excluded, the presence of a spindle
      cell component and tumor size >5 cm were each independently associated with
      decreased overall survival. The actuarial 5-year overall survival for patients
      with and without a metaplastic spindle cell component was 38%+/-15% and 89%+/-7%,
      respectively. Poor clinical outcome, therefore, is associated with the subset of
      pleomorphic carcinomas with a spindle cell metaplastic component. As the
      morphologic features of pleomorphic carcinoma can be seen in primary tumors from
      other sites, it is important to recognize this tumor as a rare variant of
      invasive breast carcinoma.

PMID- 20154590
TI  - The clinical significance of incidental chronic colitis: a study of 17 cases.
AB  - INTRODUCTION: A histologic diagnosis of chronic colitis raises a relatively
      limited differential diagnosis that includes inflammatory bowel disease, long
      standing infections, and chronic ischemia. In routine clinical practice,
      inflammatory bowel disease accounts for the majority of cases of chronic colitis.
      Although a variety of drug-induced injury patterns in the colon have been
      recognized, there are few well-documented examples of drug-induced chronic
      colitis. In this study, we report the clinical, histologic, and follow-up data on
      17 cases of histologically documented cases of chronic colitis in which a
      definitive etiologic factor could not be identified. METHODS: Using our
      electronic databases we recorded all cases of chronic colitis in adults over an 8
      year period. Patients with a history (prior or subsequent) of inflammatory bowel
      disease were excluded. Cases showing histologic features of ischemic,
      pseudomembranous, or granulomatous colitis were excluded. The biopsies were
      evaluated and semiquantitatively scored for established histologic features of
      activity and chronicity. The clinical, endoscopic, and follow-up data, including
      drug usage, was recorded. RESULTS: There were 10 males and 7 females and the mean
      age was 59 years. The majority of cases involved the cecum or ascending colon (16
      of 17 cases). A majority of patients were asymptomatic (n=11), and in others,
      indications for colonoscopy were occult blood (n=3), hematochezia (n=2), and
      melena (n=1). The most common mucosal abnormality was erythema (n=10), ulcers
      (n=3), congestion (n=3), and edematous mucosa (n=1). All cases showed histologic
      features of chronicity and showed either basal plasmacytosis (94%) or crypt
      architectural distortion (94%). Eight (47%) patients reported nonsteroidal anti
      inflammatory drugs (NSAID) use. Withdrawal of NSAIDs in 2 cases resulted in
      normalization of the colonic mucosa. On follow-up, all 17 patients were
      asymptomatic (median follow-up 42.8 mo) and did not progress to inflammatory
      bowel disease. CONCLUSIONS: We report a series of 17 histologically documented
      cases of incidental chronic colitis without a conventional etiology. However,
      both the frequent usage of NSAIDs, and normalization of mucosal changes after
      withdrawal of this drug suggest that NSAIDs may account for this cecal-based
      chronic colitis. The awareness of this histologically dramatic but clinically
      innocuous form of chronic colitis may avoid errors in mucosal biopsy diagnosis.

PMID- 20154593
TI  - Anticytokeratin CAM5.2 is not synonymous with CK8/18 monoclonal antibody; and
      anticytokeratin CAM5.2 can be a marker for cytokeratin 8 but not for cytokeratin
      18 and 19.

PMID- 20154594
TI  - Smooth muscle neoplasms of the urinary bladder: a clinicopathologic study of 51
      cases.
AB  - Smooth muscle neoplasms of the urinary bladder are relatively rare. We report the
      largest series to date examining the clinicopathologic features of leiomyomas and
      leiomyosarcomas of the bladder. This study sought to clarify several issues
      relating to smooth muscle neoplasms of the urinary bladder: (1) How to
      distinguish leiomyomas of the bladder from normal muscularis propria on
      transurethral resection (TUR) specimens; (2) Whether symplastic leiomyomas can be
      diagnosed in the bladder; (3) Can leiomyoma be definitively diagnosed on biopsy
      or TUR without the risk of there being unsampled leiomyosarcoma; and (4) Is the
      grade of leiomyosarcoma seen on biopsy or TUR heterogeneous and hence possibly
      not representative of the true grade. Thirty-one leiomyomas and 20 leiomyosarcoma
      cases of urinary bladder from 3 tertiary care medical centers were examined.
      Leiomyosarcoma cases were subdivided into low-grade and high-grade based on
      mitotic count (> or =5/10 HPF) and nuclear atypia. The mean age of the patients
      with leiomyoma and leiomyosarcoma was 52 and 58, respectively. The M:F ratio was
      significantly higher in patients with leiomyosarcoma (2:1) compared with
      leiomyoma (1:3), p<0.005. The specimen consisted of 20 TUR and 11 transurethral
      biopsies (TUBx) for leiomyomas, and 10 TUR, 3 TUBx, 5 cystectomies (Cyst), and 2
      partial cystectomies (pCyst) for leiomyosarcomas. LEIOMYOMAS: Notable features in
      leiomyomas were hyalinization (7/31), degenerative atypia (7/31), necrosis
      (4/31), myxoid changes (2/31), and focal fatty metaplasia (1/31); although no
      surface ulceration was identified. Clinical follow-up was available for 24
      patients (12 to 108 mo; mean 36 mo); 4 lost to follow-up and 3 recent cases. Two
      patients had repeat TUR within a year of the initial diagnosis with the same
      bland leiomyoma on histology, probably reflecting persistence of earlier
      unresected tumor as opposed to recurrent tumor. None of the patients were
      diagnosed with leiomyosarcoma on follow-up, including 7 cases with degenerative
      atypia. LEIOMYOSARCOMA: Of the 20 leiomyosarcomas, 8 were classified as low-grade
      and 12 as high-grade sarcomas. Histologic features included epithelioid
      morphology (5/20; 1 entirely epithelioid), tumor cell necrosis (11/20), and
      mucosal ulceration (7/20). Infiltration into the muscularis propria was seen
      predominantly as a nodular growth pattern with some cases exhibiting an irregular
      infiltrative pattern (6/10 with evaluable borders); an infiltrative pattern was
      not restricted to high-grade lesions. Lesional heterogeneity was present in only
      1 case on the same specimen, which showed both low-grade and high-grade areas.
      Another case was low grade on TUR, yet high grade at cystectomy. None of the
      cases of leiomyosarcomas had areas histologically resembling leiomyoma. Clinical
      follow-up was available for 15 patients with leiomyosarcoma (11 to 144 mo; mean
      47 mo); 3 lost to follow-up and 2 recent cases. Only 1 patient with low-grade
      sarcoma experienced 2 local recurrences treated only by TUR and is currently free
      of disease. Disease-related mortality was significantly higher in patients with
      high-grade compared with low-grade leiomyosarcomas (50% vs. none, respectively;
      P<0.001). Leiomyoma (including symplastic leiomyoma) may be diagnosed on TUR
      without risk of underdiagnosing unsampled leiomyosarcoma. High-grade
      leiomyosarcomas are highly aggressive neoplasms compared with low-grade
      leiomyosarcomas; in most cases grade can be accurately determined on TUR.

PMID- 20154595
TI  - Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil
      antitumor effect on KB cells.
AB  - Triptolide, a diterpenoid triepoxide derived from the Chinese herb Tripterygium
      wilfordii, exerts an antitumor effect in KB cancer cells through the induction of
      apoptosis. In this study, we show that triptolide possesses an anticancer effect
      on drug-sensitive parental KB cells and multidrug-resistant KB-7D and KB-tax
      cells that overexpress multidrug resistance protein and MDR, respectively. Our
      data revealed that triptolide decreases the expression of multidrug resistance
      protein and MDR in both KB-7D and KB-tax cells. It also induces apoptosis in
      these multidrug-resistant cancer cells by activating caspase-3, and decreasing
      Mcl-1 and XIAP. Triptolide not only inhibits tumor growth but also induces
      apoptosis of these drug-resistant cancer cells in xenograft mouse models.
      Moreover, we also show that triptolide combined with 5-fluorouracil could be an
      alternative strategy for chemotherapy enhancement. These results indicate the
      therapeutic value of triptolide on multidrug-resistant cells, and when combined
      with 5-fluorouracil for the enhancement of cancer therapy.

PMID- 20154596
TI  - A systematic review of quality indicators for evaluating pediatric trauma care.
AB  - OBJECTIVE: Trauma care provides injured children with life- and limb-saving
      treatment, but it is unclear if the proper tools have been developed to measure
      the quality of care delivered. We sought to systematically review the literature
      on quality indicators for evaluating pediatric trauma care. DATA SOURCES AND
      STUDY SELECTION: We searched MEDLINE (1950- January 14, 2009), EMBASE (1980-week
      2, 2009), CINAHL (1982- week 2, 2009) and The Cochrane Library (4th Quarter 2008)
      from the earliest available date to January 14, 2009, plus the Gray Literature,
      select journals by hand, reference lists, and articles recommended by experts in
      the field. Studies were selected that used one or more quality indicators to
      evaluate the quality of care delivered to patients 18 yrs of age or younger with
      a major traumatic injury. DATA EXTRACTION AND DATA SYNTHESIS: The literature
      search identified 6869 citations. Review of abstracts led to the retrieval of 538
      full-text articles for assessment; 12 articles were selected for review. Of
      these, five (42%) articles were case series and five (42%) articles were cohort
      studies. Two articles included control groups, a before-and-after case series,
      and a nonrandomized controlled trial. A total of 120 quality indicators in
      pediatric trauma care were identified, predominantly measures of prehospital and
      hospital processes and outcomes of care. We did not identify any prehospital
      structure or posthospital or secondary injury prevention quality indicators.
      Among multiple trauma patients, deficiencies in the quality of care ranged from
      8% to 45% of patients, with 6% to 32% of deaths in hospital judged to be
      preventable on peer review. CONCLUSIONS: There is limited experimental research
      regarding quality indicators in pediatric trauma care, but the literature
      suggests that deficiencies exist in the quality of care. Future research is
      needed to develop and evaluate patient-centered pediatric-specific indicators
      that cover the full spectrum of trauma care.

PMID- 20154597
TI  - Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and
      mortality in septic shock patients: results of a three-year follow-up quasi
      experimental study.
AB  - OBJECTIVES: To describe the effectiveness of the Surviving Sepsis Campaign
      bundles with regard to both implementation and outcome in patients with septic
      shock and to determine the contribution of the various elements of the bundles to
      the outcome. DESIGN: Quasi-experimental study with a historical comparison group.
      SETTING: The three medical-surgical intensive care units of an academic tertiary
      care center. PATIENTS: A total of 384 adult patients in septic shock were
      enrolled after the educational intervention (September 2005-August 2008) and 96
      patients in the historical group (June 2004-May 2005). INTERVENTION: A hospital
      wide quality improvement program based on the implementation of the Surviving
      Sepsis Campaign guidelines performed between June 2005 and August 2005.
      MEASUREMENTS AND RESULTS: In-hospital mortality was reduced from 57.3% in the
      historical group to 37.5% in the intervention group (p = .001). This difference
      remained significant after controlling for confounding factors (odds ratio, 0.50;
      95% confidence interval, 0.28-0.89). The intervention group had also lower length
      of stay for survivors in the hospital (36.2 +/- 34.8 days vs. 41.0 +/- 26.3 days;
      p = .043) and in the intensive care units (8.4 +/- 9.8 days vs. 11.0 +/- 9.5
      days; p = .004). Improvements in survival were related to the number of bundle
      interventions completed (p for trend <.001). Compliance with six or more
      interventions of the 6-hr resuscitation bundle was an independent predictor of
      survival (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.53; p
      <.001). The only single intervention with impact on mortality was the achievement
      of ScvO2 > or =70% (adjusted odds ratio, 0.62; 95% confidence interval, 0.38
      0.99; p = .048). CONCLUSIONS: The implementation of the Surviving Sepsis Campaign
      guidelines was associated with a significant decrease in mortality. The benefits
      depend on the number of interventions accomplished within the time limits. The 6
      hr resuscitation bundle showed greater compliance and effectiveness than the 24
      hr management bundle.

PMID- 20154598
TI  - Effects of cerebrovascular pressure reactivity-guided optimization of cerebral
      perfusion pressure on brain tissue oxygenation after traumatic brain injury.
AB  - OBJECTIVE: To evaluate the concept of a cerebrovascular pressure reactivity
      guided optimal cerebral perfusion pressure after traumatic brain injury by
      analyzing the relationship between optimal cerebral perfusion pressure and brain
      tissue oxygen. DESIGN: Prospective observational cohort study. SETTING:
      Neurosurgical intensive care unit of a university hospital. PATIENTS: Thirty
      eight patients after head injury. INTERVENTIONS: Continuous computerized
      monitoring of mean arterial pressure, intracranial pressure, and brain tissue
      oxygen for 5.3 +/- 2.6 days. The index of cerebrovascular pressure reactivity was
      calculated as a moving correlation coefficient between spontaneous low-frequency
      fluctuations of mean arterial pressure and intracranial pressure. Optimal
      cerebral perfusion pressure was defined as the cerebral perfusion pressure level
      with the lowest average index of cerebrovascular pressure reactivity.
      MEASUREMENTS AND MAIN RESULTS: Optimal cerebral perfusion pressure could be
      identified in 32 of 38 patients. Median optimal cerebral perfusion pressure was
      between 70 and 75 mm Hg (range, 60-100 mm Hg). Below the level of optimal
      cerebral perfusion pressure, brain tissue oxygen decreased in parallel to
      cerebral perfusion pressure, whereas brain tissue oxygen reached a plateau above
      optimal cerebral perfusion pressure. Optimal cerebral perfusion pressure
      correlated significantly with the cerebral perfusion pressure level, where brain
      tissue oxygen reached its plateau (r = .79; p < .01). Average brain tissue oxygen
      at optimal cerebral perfusion pressure was 24.5 +/- 6.0 mm Hg. CONCLUSIONS: This
      study supports the concept of cerebrovascular pressure reactivity-based
      individual optimal cerebral perfusion pressure. Driving cerebral perfusion
      pressure in excess of optimal cerebral perfusion pressure does not yield
      improvements in brain tissue oxygen after head injury and should be avoided,
      whereas cerebral perfusion pressure below optimal cerebral perfusion pressure may
      result in secondary cerebral ischemia.

PMID- 20154599
TI  - Catheter dysfunction and dialysis performance according to vascular access among
      736 critically ill adults requiring renal replacement therapy: a randomized
      controlled study.
AB  - OBJECTIVE: To compare dialysis catheter function according to catheter site.
      DESIGN: Multicenter, open, randomized controlled trial. SETTING: Nine university
      affiliated hospitals and three general hospitals in France. PATIENTS: Seven
      hundred thirty-six patients in intensive care units who required a first venous
      catheterization to perform either intermittent hemodialysis (470 patients with
      1275 sessions) or continuous renal replacement therapy (266 patients with 1003
      days). INTERVENTION: Patients randomly received either femoral (n = 370) or
      jugular (n = 366) catheterization. For the jugular site, right-side position (n =
      252) was recommended. MEASUREMENTS AND MAIN RESULTS: Time to catheter ablation
      for dysfunction, urea reduction ratio (intermittent hemodialysis), and downtime
      (continuous renal replacement therapy) were assessed for all participants and
      evaluated by randomly assigned catheterization site (femoral or jugular).
      Baseline demography and dialysis prescriptions were similar between the site
      arms. In modified intent-to-treat, catheter dysfunction occurred in 36 of 348
      (10.3%) and 38 of 342 (11.1%) patients in the femoral and jugular groups,
      respectively. The risk of catheter dysfunction did not significantly differ
      between randomized groups (hazard ratio, 1.06; 95% confidence interval, 0.67
      1.68; p = .80). Compared to the femoral site, the observed risk of dysfunction
      decreased in the right jugular position (15 of 226; 6.6%; adjusted hazard ratio,
      0.58; 95% confidence interval, 0.31-1.07; p = .09) and significantly increased in
      the left jugular position (23 of 118; 19.5%; adjusted hazard ratio, 1.89; 95%
      confidence interval, 1.12-3.21; p < .02). The postintermittent hemodialysis mean
      urea reduction ratio per session was 50.8% (standard deviation, 16.1) for femoral
      vs. 52.8% (standard deviation, 15.8) for jugular (p = .30) sites, and the median
      continuous renal replacement therapy downtime per patient-day was 1.17 hrs
      (interquartile range, 0.75-1.50) for both sites (p = .98). CONCLUSIONS: In terms
      of catheter dysfunction and dialysis performance among critically ill adults
      requiring acute renal replacement therapy, jugular site did not significantly
      outperform femoral site placement.

PMID- 20154600
TI  - Lung morphology predicts response to recruitment maneuver in patients with acute
      respiratory distress syndrome.
AB  - OBJECTIVES: The impact of recruitment maneuvers on gas exchange, hemodynamics,
      alveolar recruitment, and hyperinflation is highly variable among patients with
      acute respiratory distress syndrome. The objective was to determine whether
      differences in lung morphology, defined as differences in the pulmonary
      distribution of aeration loss, predict the response to recruitment maneuvers.
      DESIGN: Prospective study. SETTING: A 16-bed medical-surgical intensive care unit
      in a university hospital. MEASUREMENTS AND MAIN RESULTS: Nineteen consecutive
      patients with early acute lung injury/acute respiratory distress syndrome were
      studied. Computed tomography scans, respiratory mechanics, hemodynamics, and gas
      exchange were obtained at zero end-expiratory pressure during an open-lung
      ventilation (controlled mode, tidal volume 6 mL/kg of ideal body weight, positive
      end-expiratory pressure set 2 cm H2O above the lower inflection point of the
      inspiratory pressure volume curve at zero end-expiratory pressure) during a
      recruitment maneuver (continuous positive airway pressure of 40 cm H2O for 40
      secs), and, finally, 5 mins after the recruitment maneuver during open-lung
      ventilation. Nine patients presented focal and 10 presented nonfocal lung
      morphology at zero end-expiratory pressure. Recruitment maneuver-induced
      recruited volume after 5 mins of open-lung ventilation was 48 +/- 66 mL and 417
      +/- 293 mL in patients with focal and nonfocal lung morphology, respectively (p =
      .0009). Recruitment maneuver-induced alveolar hyperinflation represented 23% +/-
      14% and 8% +/- 9% of total lung volume in patients with focal and nonfocal
      morphology, respectively (p = .007). In patients with focal lung morphology,
      hyperinflated lung volume was significantly greater during and 5 mins after (316
      +/- 155 mL) than immediately before recruitment maneuvers (150 +/- 175 mL; p =
      .0407. CONCLUSION: Lung morphology at zero end-expiratory pressure predicts the
      response to recruitment maneuvers. Patients with focal lung morphology are at
      risk for significant hyperinflation during the recruitment maneuvers, and lung
      recruitment is rather limited.

PMID- 20154602
TI  - Hark back: passive immunotherapy for influenza and other serious infections.
AB  - The world is experiencing a pandemic of swine-origin influenza virus H1N1. A
      vaccine to prevent disease is now available, and millions have or will become ill
      before they can be vaccinated. The ability to use swine-origin influenza virus
      vaccines as a public health tool has been described as a "race against time."
      Oseltamivir and related drugs are being used in an effort to reduce morbidity and
      mortality, but their efficacy for treating severe influenza is suboptimal, and
      possible wide-spread emergence of oseltamivir-resistant mutants is a concern.
      Another approach for prevention and treatment of serious influenza is infusion of
      hyperimmune plasma. The United States has thousands of licensed blood product
      collection centers that produce millions of liters of plasma licensed by the Food
      and Drug Administration on an annual basis for the treatment of serious
      conditions. Immunotherapy using infusion of convalescent plasma (or hyperimmune
      intravenous immunoglobulin) has been reported to be an effective treatment for
      severe influenza and other virulent pathogens in animal models and humans. Plasma
      obtained from those that have recovered or were early recipients of vaccine
      offers a resource for production of an immediately available and potentially
      effective therapy at the local, state, and national level. Past, current, and
      future uses of immunotherapy and current advisory body recommendations for this
      approach are presented.

PMID- 20154601
TI  - Infectious risk associated with arterial catheters compared with central venous
      catheters.
AB  - BACKGROUND: Scheduled replacement of central venous catheters and, by extension,
      arterial catheters, is not recommended because the daily risk of catheter-related
      infection is considered constant over time after the first catheter days.
      Arterial catheters are considered at lower risk for catheter-related infection
      than central venous catheters in the absence of conclusive evidence. OBJECTIVES:
      To compare the daily risk and risk factors for colonization and catheter-related
      infection between arterial catheters and central venous catheters. METHODS: We
      used data from a trial of seven intensive care units evaluating different
      dressing change intervals and a chlorhexidine-impregnated sponge. We determined
      the daily hazard rate and identified risk factors for colonization using a
      marginal Cox model for clustered data. RESULTS: We included 3532 catheters and
      27,541 catheter-days. Colonization rates did not differ between arterial
      catheters and central venous catheters (7.9% [11.4/1000 catheter-days] and 9.6%
      [11.1/1000 catheter-days], respectively). Arterial catheter and central venous
      catheter catheter-related infection rates were 0.68% (1.0/1000 catheter-days) and
      0.94% (1.09/1000 catheter-days), respectively. The daily hazard rate for
      colonization increased steadily over time for arterial catheters (p = .008) but
      remained stable for central venous catheters. Independent risk factors for
      arterial catheter colonization were respiratory failure and femoral insertion.
      Independent risk factors for central venous catheter colonization were trauma or
      absence of septic shock at intensive care unit admission, femoral or jugular
      insertion, and absence of antibiotic treatment at central venous catheter
      insertion. CONCLUSIONS: The risks of colonization and catheter-related infection
      did not differ between arterial catheters and central venous catheters,
      indicating that arterial catheter use should receive the same precautions as
      central venous catheter use. The daily risk was constant over time for central
      venous catheter after the fifth catheter day but increased significantly over
      time after the seventh day for arterial catheters. Randomized studies are needed
      to investigate the impact of scheduled arterial catheter replacement.

PMID- 20154603
TI  - Healthcare personnel and nosocomial transmission of pandemic 2009 influenza.
AB  - Knowledge regarding the modes of transmission of pandemic 2009 H1N1 influenza
      continues to develop, as do recommendations for the prevention of spread within
      healthcare facilities. The adoption of the most prudent, multifaceted approaches
      is recommended until there is significant evidence to reduce protective measures.
      The greatest threat to healthcare personnel and patients appears to be exposure
      to patients, healthcare personnel, or visitors who have not been recognized as
      contagious. The processes used within healthcare facilities must hold this
      concept central to any infection control plan and act in a preventive manner.
      This article focuses on the development of an algorithm for intensive care unit
      intake precautions, based on the early identification of potential source
      patients, as well as appropriate selection and adequate use of personal
      protective equipment. Visitor management, hand and respiratory hygiene, and cough
      etiquette have been used as measures to decrease the spread of infection.
      Vaccination of healthcare personnel, combined with work furlough for ill workers,
      is also explored. Recommendations include the elimination of potential exposures,
      engineering and administrative controls, and utilization of personal protective
      equipment.

PMID- 20154604
TI  - Therapeutic accessibility of caspase-mediated cell death as a key pathomechanism
      in indirect acute lung injury.
AB  - OBJECTIVE: Indirect acute lung injury is associated with high morbidity and
      mortality. However, the underlying pathophysiology is only marginally understood,
      and so far no pathophysiologic-based remedy exists. We hypothesized that
      apoptosis of lung epithelial cells is a pathophysiological relevant process in
      the development of indirect acute lung injury and that it should be accessible to
      a siRNA-based therapeutic intervention in vivo. DESIGN: Prospective, randomized,
      controlled animal study. SETTING: Basic science laboratory of a university
      affiliated level one trauma center. SUBJECTS: Male C3H/HeN mice, 8 wks old, n =
      121. INTERVENTIONS: First, siRNA sequences to knock-down caspase-3 expression at
      a RNA and protein level were evaluated in vitro. Then, C3H/HeN mice were
      subjected to hemorrhagic shock, after which they received either a caspase-3
      siRNA or a control/nonsense siRNA. Subsequently, they were then subjected to
      polymicrobial sepsis (induced by cecal ligation and puncture). MEASUREMENTS AND
      MAIN RESULTS: Twelve and 24 hrs after sepsis, increased lung epithelial apoptosis
      was observed, as evidenced by active caspase-3 Western blotting, caspase-3, TUNEL
      , and M-30 immunohistochemistry. Hallmarks of acute lung injury, such as
      increased concentrations of pulmonary cytokines/chemokines, lung protein leakage,
      myeloperoxidase activity, and altered lung histology, were evident in response to
      these insults. The single intratracheal instillation of caspase-3 siRNA not only
      attenuated lung apoptosis and inflammation but also ameliorated the development
      of acute lung injury in treated mice. Most interestingly, this experimental
      therapeutic approach markedly improved 10-day survival of hemorrhaged septic
      mice. CONCLUSIONS: Apoptosis of lung epithelial cells is a relevant
      pathomechanism in the development of hemorrhage-induced indirect septic acute
      lung injury, and caspase-3 appears to be a valuable therapeutic target accessible
      by siRNA treatment in vivo.

PMID- 20154605
TI  - Peritonitis-induced peroxynitrite and lung damage depends on c-Jun NH2-terminal
      kinase signaling of hematopoietic cells.
AB  - OBJECTIVES: Abdominal sepsis is a common, life-threatening condition in
      critically ill patients, and pseudomonas peritonitis remains a serious clinical
      complication of peritoneal dialysis. This study was performed to determine
      whether peritonitis induces lung damage through the c-Jun NH2-terminal kinase.
      DESIGN: : Prospective, experimental study. SETTING: Research laboratory at a
      university hospital. SUBJECTS: Peritonitis models in the mice. INTERVENTIONS:
      Wild-type, c-Jun NH2-terminal kinase1, and c-Jun NH2-terminal kinase1 mice were
      subjected to peritonitis. A c-Jun NH2-terminal kinase inhibitor, SP600125 or
      leflunomide, was administered to mice immediately after peritonitis. MEASUREMENTS
      AND MAIN RESULTS: The changes of plasma dihydrorhodamine 123 oxidation level, the
      myeloperoxidase activity, and extravasations of Evans blue dye of lung in wild
      type mice with or without c-Jun NH2-terminal kinase inhibitor; c-Jun NH2-terminal
      kinase1 mice and c-Jun NH2-terminal kinase1 mice; and chimeric mice (wild-type -
      > wild-type, c-Jun NH2-terminal kinase1 --> wild-type) with Pseudomonas
      aeruginosa-induced peritonitis were determined to evaluate the role of c-Jun NH2
      terminal kinase signaling of the hematopoietic cells in peritonitis-induced lung
      damage. Our results showed that peritonitis induced dihydrorhodamine 123
      oxidation, myeloperoxidase activity, activator protein-1 (AP-1) DNA binding
      activity, phosphorylated-c-Jun NH2-terminal kinase and inducible nitric oxide
      synthase expression, and Evans blue dye extravasations in lungs, and
      administration of specific c-Jun NH2-terminal kinase inhibitor decreased the
      peritonitis-induced dihydrorhodamine 123 oxidation and lung damage. Also, both c
      Jun NH2-terminal kinase1 and c-Jun NH2-terminal kinase1 mice showed a decreased
      dihydrorhodamine 123 oxidation and lung damage after peritonitis. Finally,
      dihydrorhodamine 123 oxidation, reactive oxygen species, inducible nitric oxide
      synthase expression, and lung damage were decreased in c-Jun NH2-terminal kinase1
      --> wild-type but not in wild-type --> c-Jun NH2-terminal kinase1 chimeric mice.
      CONCLUSIONS: Collectively, our data suggest that peritonitis-induced inducible
      nitric oxide synthase expression, peroxynitrite production, and lung damage
      depend on the c-Jun NH2-terminal kinase signaling of the hematopoietic cells.

PMID- 20154606
TI  - Infliximab attenuates early myocardial dysfunction after resuscitation in a swine
      cardiac arrest model.
AB  - OBJECTIVE: Left ventricular dysfunction after successful cardiopulmonary
      resuscitation contributes to early death after resuscitation. Proinflammatory
      cytokines are known to decrease myocardial function, and tumor necrosis factor
      alpha has been shown to increase after successful resuscitation. We hypothesized
      that blocking the effects of tumor necrosis factor-alpha with infliximab would
      prevent or minimize postresuscitation cardiac dysfunction. DESIGN: Randomized,
      placebo-controlled comparative study. SETTING: Large animal research laboratory.
      SUBJECTS: Twenty-eight anesthetized and instrumented domestic male swine
      (Yorkshire and Yorkshire/Hampshire mix; weight, 35-45 kg). INTERVENTIONS:
      Infusion of infliximab (5 mg/kg) or normal saline after resuscitation from
      ventricular fibrillation cardiac arrest. MEASUREMENTS AND MAIN RESULTS:
      Hemodynamic variables, indices of left ventricular function, and tumor necrosis
      factor-alpha were measured before and after 8 mins of cardiac arrest during the
      early postresuscitation period (3 hrs). Within 5 mins of restoration of
      spontaneous circulation, 14 animals received infliximab, 5 mg/kg, infused over 30
      mins. Fourteen animals received an infusion of normal saline. Inotropes and
      vasopressors were not administered to either group after resuscitation. Tumor
      necrosis factor-alpha increased after restoration of circulation and remained
      elevated throughout the observation period. Differences between groups were not
      significant. Interleukin-1beta concentration did not change significantly during
      the observation period in either study group. Mean arterial pressure and stroke
      work were significantly greater in the infliximab group within 30 mins of
      resuscitation, and these differences were sustained throughout the 3-hr
      postresuscitation period. The effect of tumor necrosis factor-alpha blockade was
      evident only in animals with a significant increase (doubling) in plasma tumor
      necrosis factor-alpha at 30 mins after arrest. CONCLUSION: Tumor necrosis factor
      alpha plays a role in cardiac dysfunction after arrest and infliximab may
      attenuate or prevent postresuscitation myocardial dysfunction when administered
      immediately after resuscitation.

PMID- 20154607
TI  - Activated protein C and hospital mortality in septic shock: a propensity-matched
      analysis.
AB  - OBJECTIVE: Evidence regarding the efficacy and safety of human recombinant
      activated protein C in severe sepsis is limited, especially outside of clinical
      trials. We sought to compare the outcomes of patients with septic shock who
      received early treatment with activated protein C to those who did not. DESIGN,
      SETTING, AND PATIENTS: A retrospective cohort study at 404 U.S. hospitals. We
      studied 33,749 patients with sepsis who were admitted to intensive care and
      administered antibiotics and vasopressors within 2 days of admission.
      MEASUREMENTS AND MAIN RESULTS: Hospital mortality, intracranial and
      gastrointestinal hemorrhage, major transfusion. Compared to the entire cohort,
      the 1576 activated protein C-treated patients included in the matched analysis
      were younger (mean age, 61 vs. 67), more likely to be white (70% vs. 63%), and
      had fewer comorbidities. Treated patients were more likely to require mechanical
      ventilation (77% vs. 48%), to be administered two or more vasopressors (68% vs.
      41%), to undergo pulmonary artery catheterization (9% vs. 4%), and to die in the
      hospital (40.7% vs. 38.1%). In a propensity-matched sample in which all
      covariates achieved balance, receipt of activated protein C was associated with
      reduced hospital mortality (40.7% vs. 46.6%; risk ratio, 0.87; 95% confidence
      interval, 0.80-0.95). This result was insensitive to a hypothetical unmeasured
      confounder. A similar pattern was observed across groups stratified by age and
      number of organ-supportive therapies. Four activated protein C-treated patients
      (0.25%) had hemorrhagic stroke, 107 (6.8%) had gastrointestinal bleeding, and
      five (0.3%) required major transfusion. CONCLUSIONS: Among patients presenting
      with septic shock, early treatment with activated protein C may be associated
      with reduced hospital mortality.

PMID- 20154609
TI  - Functional consequences of sarcopenia and dynapenia in the elderly.
AB  - PURPOSE OF REVIEW: The economic burden due to the sequela of sarcopenia (muscle
      wasting in the elderly) are staggering and rank similarly to the costs associated
      with osteoporotic fractures. In this article, we discuss the societal burden and
      determinants of the loss of physical function with advancing age, the physiologic
      mechanisms underlying dynapenia (muscle weakness in the elderly), and provide
      perspectives on related critical issues to be addressed. RECENT FINDINGS: Recent
      epidemiological findings from longitudinal aging studies suggest that dynapenia
      is highly associated with both mortality and physical disability even when
      adjusting for sarcopenia indicating that sarcopenia may be secondary to the
      effects of dynapenia. These findings are consistent with the physiologic
      underpinnings of muscle strength, as recent evidence demonstrates that
      alterations in muscle quantity, contractile quality and neural activation all
      collectively contribute to dynapenia. SUMMARY: Although muscle mass is essential
      for regulation of whole body metabolic balance, overall neuromuscular function
      seems to be a critical factor for maintaining muscle strength and physical
      independence in the elderly. The relative contribution of physiologic factors
      contributing to muscle weakness are not fully understood and further research is
      needed to better elucidate these mechanisms between muscle groups and across
      populations.

PMID- 20154608
TI  - Anabolic and catabolic pathways regulating skeletal muscle mass.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss recent findings as
      they pertain to anabolic and catabolic-signaling pathways involved in the
      regulation of adult skeletal muscle mass. RECENT FINDINGS: Research conducted
      over the past few years has continued to refine our understanding of the pathways
      that govern skeletal muscle mass, in particular the mTOR, FoxO and NF-kappaB
      pathways. Alternative signaling pathways have also emerged as important
      regulators of muscle mass such as the beta-catenin pathway. SUMMARY: A better
      understanding of the anabolic and catabolic processes which regulate skeletal
      muscle mass is critical for the development of more effective therapeutics to
      prevent the loss of muscle with disuse, aging and disease.

PMID- 20154610
TI  - Genetic determinants of apolipoprotein B-100 kinetics.
AB  - PURPOSE OF REVIEW: We review stable isotope tracer studies of apolipoprotein B
      100 (apoB) kinetics concerning genetic polymorphisms and mutations that affect
      human lipoprotein metabolism. RECENT FINDINGS: In obese men, the allelic
      combination of the apoB signal peptide, SP24, and cholesteryl ester transfer
      protein, CETP B1B1, is independently associated with lower VLDL apoB secretion.
      Microsomal triglyceride transfer protein -493G/T carriers have reduced IDL apoB
      and LDL apoB production as compared with controls. Mutations in cholesterol
      transporters (ATP-binding cassette transporter G8 and Niemann-Pick C1 Like 1) are
      associated with reduced VLDL apoB secretion and increased LDL apoB production and
      catabolism. The ATP-binding cassette transporter G8 400K variant is a
      significant, independent predictor of VLDL apoB secretion. Mutations in lipases
      (lipoprotein lipase and hepatic lipase) and transfer proteins (lecithin
      cholesterol acyltransferase and cholesteryl ester transfer protein) alter their
      functional activity, which impact on VLDL and LDL kinetics. SUMMARY: Mutations in
      genes that regulate intrahepatic apoB assembly and lipid substrate availability
      to the liver impact on VLDL apoB secretion. Lipoprotein tracer studies can
      provide functional insight into the potential impact of genetic polymorphisms in
      regulating apoB metabolism in humans.

PMID- 20154612
TI  - PhenX: a toolkit for interdisciplinary genetics research.
AB  - PURPOSE OF REVIEW: To highlight standard PhenX (consensus measures for Phenotypes
      and eXposures) measures for nutrition, dietary supplements, and cardiovascular
      disease research and to demonstrate how these and other PhenX measures can be
      used to further interdisciplinary genetics research. RECENT FINDINGS: PhenX
      addresses the need for standard measures in large-scale genomic research studies
      by providing investigators with high-priority, well established, low-burden
      measurement protocols in a web-based toolkit (https://www.phenxtoolkit.org).
      Cardiovascular and Nutrition and Dietary Supplements are just 2 of 21 research
      domains and accompanying measures included in the PhenX Toolkit. SUMMARY: Genome
      wide association studies (GWAS) provide promise for the identification of genomic
      markers associated with different disease phenotypes, but require replication to
      validate results. Cross-study comparisons typically increase statistical power
      and are required to understand the roles of comorbid conditions and environmental
      factors in the progression of disease. However, the lack of comparable
      phenotypic, environmental, and risk factor data forces investigators to infer and
      to compare metadata rather than directly combining data from different studies.
      PhenX measures provide a common currency for collecting data, thereby greatly
      facilitating cross-study analysis and increasing statistical power for
      identification of associations between genotypes, phenotypes, and exposures.

PMID- 20154611
TI  - Adaptive genetic variation and heart disease risk.
AB  - PURPOSE OF REVIEW: Obesity, dyslipidemia and cardiovascular disease are complex
      and determined by both genetic and environmental factors and their inter
      relationships. Many associations from genome-wide association studies and
      candidate gene approaches have described a multitude of polymorphisms associating
      with lipid and obesity phenotypes but identified genetic variants account for
      only a small fraction of phenotypic variation. RECENT FINDINGS: That many
      genotype-phenotype associations involve variants under positive selection and
      that those variants respond to environmental cues together suggest prominent
      roles for both genetic adaptation and their interactions with the environment.
      Adaptive genetic variations interacting with environment modulate disease
      susceptibility but the level to which those variants contribute to dyslipidemia
      and obesity and how environmental factors, especially diet, alter the genetic
      association is not yet completely known. SUMMARY: It is evident that genetic
      variants under positive selection make important contributions to obesity and
      heart disease risk. Advances in resequencing the entire human genome will enable
      accurate identification of adaptive variants. Considering interactions between
      environmental factors and genotypes will empower both genome-wide association
      studies and characterization of the relationship between positive selection and
      the obese and dyslipidemic conditions.

PMID- 20154613
TI  - ABC transporters: lipid transport and inflammation.

PMID- 20154614
TI  - The nature of brain dysfunction in autism: functional brain imaging studies.
AB  - PURPOSE OF REVIEW: Functional magnetic resonance imaging studies have had a
      profound impact on the delineation of the neurobiologic basis for autism.
      Advances in fMRI technology for investigating functional connectivity, resting
      state connectivity, and a default mode network have provided further detail about
      disturbances in brain organization and brain-behavior relationships in autism to
      be reviewed in this article. RECENT FINDINGS: Recent fMRI studies have provided
      evidence of enhanced activation and connectivity of posterior, or parietal
      occipital, networks and enhanced reliance on visuospatial abilities for visual
      and verbal reasoning in high functioning individuals with autism. Evidence also
      indicates altered activation in frontostriatal networks for cognitive control,
      particularly involving anterior cingulate cortex, and altered connectivity in the
      resting state and the default mode network. The findings suggest that the
      specialization of many cortical networks of the human brain has failed to develop
      fully in high functioning individuals with autism. SUMMARY: This research
      provides a growing specification of to the neurobiologic basis for this complex
      syndrome and for the co-occurrence of the signs and symptoms as a syndrome. With
      this knowledge has come new neurobiologically based opportunities for
      intervention.

PMID- 20154615
TI  - Advances in the early detection of autism.
AB  - PURPOSE OF REVIEW: Early detection and diagnosis of autism spectrum disorders
      (ASDs) allows opportunities for children and their families to benefit more fully
      from early supports and interventions. RECENT FINDINGS: Recent advances in early
      detection research have resulted from prospective studies of high-risk infants
      and large ASD screening studies conducted in community settings. With improvement
      in early detection of autism, exciting progress has been made in establishing the
      efficacy of ASD-specific interventions for toddlers as young as 18 months on the
      basis of controlled clinical trials. SUMMARY: There has been increasing emphasis
      on opportunities to link early behavioral expression to the underlying
      neurobiology of ASD, potentially bringing us closer to the fundamental mechanisms
      underlying this disorder.

PMID- 20154616
TI  - Indications and outcomes of intrauterine surgery for fetal malformations.
AB  - PURPOSE OF REVIEW: Although the efficacy of intrauterine intervention has been
      clearly demonstrated for some conditions, such as twin to twin transfusion
      syndrome and twin reversal arterial perfusion, it is still to be determined as
      treatment of congenital diaphragmatic hernia, cardiac defects, lower urinary
      tract obstruction and sacrococcygeal teratoma. The aim of the present study was
      to review literature concerning the benefits and outcomes of fetal intervention
      for these anomalies together with its limitations and controversies. RECENT
      FINDINGS: Only one randomized clinical trial, which compared prenatal versus
      postnatal treatment for congenital diaphragmatic hernia, was performed. For the
      other anomalies, small series were described and showed that fetal surgery
      drastically changes the natural history of the discussed anomalies, thus it
      prevents the progression of a disorder that is likely to be fatal. However,
      controversies exist with regard to operating timing and selection criteria of
      fetuses that may benefit from fetal surgery. SUMMARY: Further investigations are
      needed with regard to the definition of appropriate operating timing and
      standardization of selection criteria. Multicenter randomized trials are also
      necessary in order to define whether fetal surgery is associated with better
      outcomes as compared with postnatal treatment.

PMID- 20154617
TI  - Chorionic villus sampling: technique and training.
AB  - PURPOSE OF REVIEW: Over the past decade, first trimester screening has become the
      gold standard prenatal screening modality in the developed world. This shift
      toward earlier screening would not be possible without the availability of early
      diagnosis, namely, chorionic villus sampling (CVS). The purpose of this review is
      to highlight recent updates related to CVS technique, potential complications,
      and training. RECENT FINDINGS: Recent data highlight the importance of operator
      experience in reducing CVS-related complications and argues for the
      'centralization' of CVS in experienced centers. On the other hand, despite over
      30 years of clinical practice, there is still no consensus regarding optimal CVS
      technique and some variation exists between CVS providers. Moreover, there is a
      deficiency in adequate infrastructure geared toward the training and
      certification of future CVS providers. SUMMARY: CVS is the gold standard method
      of first trimester prenatal diagnosis. Recent data suggest that CVS loss rates
      are lower than what was previously reported and are lowest in centers that
      perform a large number of procedures. The 'centralization' of this specialized
      procedure also offers the perfect opportunity for the safe, ongoing training of
      future CVS providers.

PMID- 20154619
TI  - Advances in the systemic treatment of head and neck cancers.
AB  - PURPOSE OF REVIEW: To summarize the recent literature on the treatment of
      recurrent and metastatic squamous cell carcinoma of the head and neck. RECENT
      FINDINGS: Multiple targeted therapies and novel combinations of chemotherapeutic
      agents were tested. SUMMARY: In a large randomized phase III trial, the addition
      of cetuximab to platin-based chemotherapy led to a significant prolongation of
      overall survival. The combination of cetuximab and platin/5-fluorouracil should
      be considered the current standard first-line regimen. In contrast, the results
      with oral tyrosine kinase inhibitors and other targeted agents have been
      disappointing thus far.

PMID- 20154618
TI  - Recent updates in renal cell carcinoma.
AB  - PURPOSE OF REVIEW: The review will examine the recent advances in our
      understanding of the genetic and molecular events that shape this cancer, and
      overview the emerging targeted therapies that have altered the landscape for
      renal cell carcinoma (RCC) patients. RECENT FINDINGS: The incidence of RCC
      continues to rise, making it the 7th and 8th most common cancer among men and
      women in the US, respectively. Von Hippel-Lindau (VHL) gene loss is an important
      factor in the development of clear cell RCC, however: loss of VHL can result in
      tumors which express both HIF1 and HIF2, or HIF2 alone, correlating with distinct
      pathway activities. Invasive tumors demonstrating loss of VHL consistently
      demonstrate additional genetic changes, which appear to be essential for tumor
      progression. Targeted therapies have demonstrated improvements in overall
      survival. New ways to radiographically measure the tumor response to these
      treatments may provide additional information about a drug's activity in an
      individual patient. Vascular endothelial growth factor receptor tyrosine kinase
      inhibitors are still being investigated in the adjuvant setting. SUMMARY: The
      field of RCC biology continues to rapidly change. As new targeted strategies to
      control this cancer evolve, so do both the clinical strategies, and the
      strategies to measure response and predict outcome.

PMID- 20154620
TI  - Coagulation, platelet activation and thrombosis in xenotransplantation.
AB  - PURPOSE OF REVIEW: Xenotransplantation may become clinically feasible once the
      mechanisms of graft loss and rejection are better understood. Inflammatory
      reactions to vasculature of grafted pig organs and pancreatic islets have been
      linked to procoagulant activation and consumption with resulting thrombosis that
      precludes long-term function. Although development of alpha-1,3
      galactosyltransferase gene-knockout swine with removal of a dominant xenoantigen
      has been an important advance, major problems still persist. RECENT FINDINGS:
      Consumptive coagulopathy and platelet sequestration are initiated by immune
      responses associated with xenograft rejection and are exacerbated by putative
      intrinsic functional incompatibilities. Thrombotic processes together with
      progressive xenograft microangiopathy and infarction are intertwined with humoral
      immune reactions that may be secondary, at least in part, to 'natural' or
      elicited nongalactosyl antibodies. These immune responses are further exacerbated
      by the documented intrinsic molecular incompatibilities in the vascular
      regulation of blood clotting and extracellular nucleotide homeostasis between
      discordant species. Hence, limited benefits have been achieved with currently
      available pharmacological antithrombotics and anticoagulants. SUMMARY: Proposed
      strategies to tackle this problem will include optimal immunosuppressive
      interventions, attempts to induce tolerance, judicious and more effective use of
      anti-thrombotics with development of mutant swine either transgenic for human
      anticoagulants and thromboregulatory factors or null for defined porcine
      procoagulants.

PMID- 20154621
TI  - Denial of hepatic transplantation on the basis of smoking: is it ethical?
AB  - PURPOSE OF REVIEW: There is disagreement and inconsistency between liver
      transplant programs regarding the acceptance or rejection of smokers as
      candidates for transplantation. This article reviews the outcome data for
      transplanted smokers, the rate of maintained abstinence from cigarettes by
      smokers who have quit and the ethics of using tobacco use as a transplant
      selection criterion. RECENT FINDINGS: Consistent with earlier studies, recently
      published articles continue to demonstrate an increased risk of noncutaneous
      malignancies, higher rates of graft arterial thrombosis and a higher mortality
      rate in liver transplant patients who smoke as compared with nonsmokers. There is
      a significant rate of relapse to smoking after transplantation, and the rates are
      higher among patients with alcoholic liver disease. Recent studies have shown
      that 10-16% of patients with biochemical verification of active smoking deny
      their tobacco use when interviewed for transplant consideration. Although
      extensively, if not universally, used to exclude transplant candidates, a recent
      study of marijuana use showed no difference in mortality outcomes as compared
      with nonusers. SUMMARY: With the exception of one recent study, there is
      substantial literature to support increased morbidity and mortality among
      posthepatic transplant smokers.

PMID- 20154622
TI  - The relentless and persistent global threat of a range of pulmonary infections.

PMID- 20154623
TI  - Lung disease caused by nontuberculous mycobacteria.
AB  - PURPOSE OF REVIEW: Although the incidence of tuberculosis has reduced in
      developed countries, there is a growing interest in nontuberculous mycobacteria
      (NTM) as a cause of lung disease. However, NTM are a heterogeneous group and most
      of the data come from only three species: Mycobacterium avium complex,
      Mycobacterium kansasii and Mycobacterium abscessus. Still, information about
      these three species is confusing because it is based mainly on retrospective
      studies and series of clinical cases performed in developed countries. In recent
      years, new information has appeared about other species and the pathogenesis of
      NTM. RECENT FINDINGS: Epidemiological studies show that NTM infection is a
      worldwide phenomenon with an increasing presence in developing countries perhaps
      because of the implementation of tap water. Women with characteristic phenotype
      are at higher risk of acquiring NTM infection along with patients with defects on
      cystic fibrosis transmembrane conductance regulators. New studies on
      Mycobacterium fortuitum, Mycobacterium xenopi, Mycobacterium szulgai and
      Mycobacterium simiae indicate that the American Thoracic Society criteria for
      diagnosing NTM disease may not be useful for all species of NTM. SUMMARY: New
      multicentric and prospective studies are needed to clarify the pathogenesis and
      treatment of NTM. These organisms form a numerous and heterogeneous group and
      each species should be studied separately.

PMID- 20154624
TI  - Drug-resistant and extensively drug-resistant tuberculosis in southern Africa.
AB  - PURPOSE OF REVIEW: Drug-resistant tuberculosis (TB) is of increasing global
      concern. One of the hardest hit regions is southern Africa. This study focuses on
      a concise update on recently published developments in the field. RECENT
      FINDINGS: There is mounting evidence from high-coprevalence areas that the TB and
      HIV pandemics must be viewed as an entity and tackled together. In that context,
      it has become clear that a shift may be required from standard hospital-based
      models of care towards community-based approaches. Innovative rapid diagnostics
      to detect TB drug resistance suitable for the use in resource-poor settings and
      novel drugs effective against drug-resistant Mycobacterium tuberculosis strains
      are currently developed. SUMMARY: In order to allow for a maximum impact of novel
      interventions on the problem of multidrug-resistant and extensively drug
      resistant TB, public health systems and existing TB programs must be strengthened
      significantly.

PMID- 20154625
TI  - Bacterial community-acquired pneumonia in HIV-infected patients.
AB  - PURPOSE OF REVIEW: In this review, we focus on the clinical features, diagnosis,
      outcome and management of bacterial community-acquired pneumonia (BCAP) in HIV
      infected patients, with particular attention to the most recent findings in this
      area. RECENT FINDINGS: Clinical features of BCAP are often atypical in HIV
      infected individuals, especially when liver cirrhosis is also present.
      Streptococcus pneumoniae is the most common causative agent and is frequently
      associated with bacteriemic disease even in low-risk patients according to
      pneumonia severity index. An etiologic diagnosis is obtained in an average 35% of
      cases with standard culture methods. In such conditions, urinary antigen test for
      S. pneumoniae identification may help in reaching a rapid and etiologic
      diagnosis. CD4 cell count should be carefully considered in HIV patients with
      BCAP. In consideration of their high mortality risk, patients with a CD4 cell
      count of less than 200 cells/mul should be hospitalized, whereas those with a CD4
      cell count of at least 200 cells/mul could be managed according to pneumonia
      severity index score. Empiric antibiotic therapy should include a combination of
      a beta-lactam and a macrolide or a respiratory fluoroquinolone alone. Finally,
      prevention strategies should include lifestyle modification, highly active
      antiretroviral therapy access and adherence programs and the implementation of
      pneumococcal vaccination. SUMMARY: A correct diagnosis and management together
      with a comprehensive approach to preventive measures, including lifestyle
      modification, highly active antiretroviral therapy access and adherence programs
      and the implementation of pneumococcal vaccination, are key factors to reduce
      BCAP incidence and mortality in HIV-infected patients.

PMID- 20154626
TI  - Comparison of CT head interpretation between emergency physicians and
      neuroradiologists.
AB  - Cranial computed tomography (CT) of the head is widely used in the emergency
      department 24 h a day. We compared the accuracy of CT head interpretation between
      staff emergency physicians (EPs) and neuroradiologists. We conducted a health
      records review of patients who required head CT in the emergency department. Two
      independent reviewers rated disagreement as clinically normal, significant, or
      clinically insignificant findings using published definition criteria. We
      calculated concordance and prepared descriptive and kappa statistics with 95%
      confidence intervals using SAS 9.1 software. We included 442 for this study. CT
      heads were classified as: normal or nonacute 81.5% (360 cases), insignificant
      3.8% (17 cases), and significant 14.7% (65 cases). The weighted kappa for
      agreement was 0.83 (95% confidence interval 0.76-0.90). None of these patients
      had adverse outcomes related to EP misinterpretation of the CT head. In
      conclusion, clinically important findings on CT head are not commonly missed by
      our EPs and patients rarely have inappropriate disposition.

PMID- 20154627
TI  - In patients with HCV genotype 2 or 3 infection and RVR 14 weeks treatment is
      noninferior to 24 weeks. Pooled analysis of two Scandinavian trials.
AB  - AIM: To compare 14 and 24 weeks treatment to patients with HCV genotype 2 or 3
      infection and rapid virological response (RVR). MATERIALS AND METHODS: Patients
      included in two Scandinavian trials, one nonrandomized pilot trial (n=122) and
      one randomized controlled trial (RCT) (n=428) were entered into a pooled
      database. In both trials treatment naive patients with genotype 2 or 3 were
      treated with pegylated interferon alpha 2b (1.5 microg/kg, subcutaneous) weekly
      and ribavirin (800-1400 mg, orally) daily. Primary endpoint was sustained
      virological response (SVR). RVR was defined as HCV RNA less than 50 IU/ml after 4
      weeks of treatment. In the pilot trial all patients with RVR were treated for 14
      weeks and in the RCT patients with RVR were randomised to either 14 or 24 weeks
      treatment. Patients treated per protocol were included in the primary analysis.
      The noninferiority margin was set to be 10% between the two groups with a one
      sided 5% significance level. RESULTS: In patients with RVR and genotype 2 or 3
      SVR was obtained in 181 of 199 (91.0%) and 93 of 98 (94.9%) after 14 and 24 weeks
      treatment, respectively. The observed difference in SVR rates was 3.9% (90%
      confidence interval: +1 to -8.8). The relapse rate was highest among those older
      than 40 years and those with genotype 3 and high viral load, but prolongation of
      treatment from 14 to 24 weeks did not reduce the relapse rate substantially in
      any of these groups. CONCLUSION: In patients with HCV genotype 2 or 3 infection
      and RVR 14 weeks treatment is noninferior to 24 weeks.

PMID- 20154628
TI  - Committee report: Method for evaluating conditions nominated for population-based
      screening of newborns and children.
AB  - The Secretary's Advisory Committee on Heritable Disorders in Newborns and
      Children is charged with evaluating conditions nominated for addition to the
      uniform screening panel and consequently making recommendations to the secretary
      of the US Department of Health and Human Services. This report describes the
      framework by which the committee approaches its task. Key decision nodes include
      initial review of every nomination to determine whether conditions are amenable
      for systematic evidence review, review of systematic evidence reviews conducted
      by the committee's external review group, and deliberation and formal
      recommendation for addition or exclusion to the uniform panel. Data analyzed
      include the accuracy and specificity of screening and diagnostic tests for
      nominated disorders, the extent of predicted health benefits, harms impact on
      disease course, and cost from early diagnosis and treatment. The committee
      process is guided by approaches used by similar entities, but more flexible
      criteria are sometimes needed to accommodate data limitations stemming from the
      rarity of many of these conditions. Possible outcomes of committee review range
      from recommendation to add a nominated condition to the uniform panel; provide
      feedback on specific gaps in evidence that must be addressed before making a
      decision; or rejection of a nomination (e.g., because of identified harms). The
      committee's structured evidence-based assessment of nominated conditions supports
      a consistently rigorous, iterative and transparent approach to its making
      recommendations regarding broad population-based screening programs for rare
      conditions in infants and children.

PMID- 20154629
TI  - An evidence development process for newborn screening.

PMID- 20154630
TI  - Connexin-26-associated deafness: phenotypic variability and progression of
      hearing loss.
AB  - PURPOSE: To evaluate genotype-phenotype correlation over time for a cohort of
      children with connexin-26 (GJB2)-associated autosomal recessive hearing loss.
      METHODS: Fifty-two children were identified from a database of individuals with
      homozygous or compound heterozygous mutations in GJB2 and subjected to chart
      review of their otolaryngologic and serial audiometric evaluations. Genotype
      phenotype correlations were identified among the members of this group by
      appropriate statistical analyses. RESULTS: Hearing loss was most severe in
      individuals with two truncating mutations in GJB2 and mildest in those with two
      nontruncating mutations. Progressive hearing loss was seen directly by serial
      audiometry in 24% of all subjects, and suggested in a total of 28% when those
      with normal newborn hearing screens and subsequent hearing loss were included.
      Progression was particularly common among carriers of the p.V37I allele either in
      homozygosity or in compound heterozygosity with a truncating allele; these
      children are primarily of Asian descent and demonstrate mild, slowly progressive
      hearing loss. CONCLUSIONS: Phenotype in GJB2-associated hearing loss is
      correlated with genotype, with truncating mutations giving rise to more severe
      hearing loss. Progression of hearing loss is not uncommon, especially in
      association with the p.V37I allele. These results suggest that close audiometric
      follow-up is warranted for patients with GJB2-associated recessive hearing loss.

PMID- 20154631
TI  - The profile of patients and current practice of treatment of upper limb muscle
      spasticity with botulinum toxin type A: an international survey.
AB  - To document the current practice in relation with the treatment of patients with
      upper limb spasticity with botulinum toxin type A to inform future research in
      this area. We designed an international, cross-sectional, noninterventional
      survey of current practice. Nine hundred and seventy-four patients from 122
      investigational centres in 31 countries were studied. Most patients were over 40
      years old and had a stroke. Improvement of active function was the most frequent
      treatment goal in the first 3 months after the onset of upper limb spasticity,
      but was less common than passive function in the chronic stage. Pain relief was a
      common goal in both the stages. As a rule, clinicians intended to assess the
      effectiveness of treatment with impairment level scales. Functional outcome
      measures seem to be rarely used in clinical practice. The use of these measures
      should be encouraged to assess whether the reduction in muscle tone translates
      into functional benefit to patients and their caregivers.

PMID- 20154632
TI  - Prosthetic valve endocarditis.
AB  - Prosthetic valve endocarditis (PVE) is associated with a high mortality during
      the early and midterm follow-up despite diagnostic and therapeutic improvements;
      its incidence is increasing and reaches 20-30% of all infective endocarditis
      episodes. In this review, changes in epidemiology, microbiology, diagnosis and
      therapy that have evolved in the past few years are analyzed. Staphylococci (both
      Staphylococcus aureus and coagulase-negative Staphylococcus) have emerged as the
      most common cause of PVE and are associated with a severe prognosis. Moreover,
      diagnosis may often be difficult because of its complications and extracardiac
      manifestations; thus, a comprehensive assessment of the clinical,
      echocardiographic and laboratory data must be performed. Early PVE, comorbidity,
      severe heart failure and new prosthetic dehiscence are predictors of mortality.
      Therapy is not indicated by evidence-based recommendations but mostly on
      identification of the high-risk conditions. A PVE is a common indication for
      surgery, whereas medical treatment alone may be achieved in a few instances.
      Systematic prophylaxis should be used to prevent this severe complication of
      cardiac valve replacement.

PMID- 20154633
TI  - Pheochromocytoma presenting as inverted Takotsubo cardiomyopathy: a case report
      and review of the literature.
AB  - The classical entity of Takotsubo cardiomyopathy is well established in the
      literature, but mechanisms explaining it remain unelucidated. Recently, the
      uncommon inverted Takotsubo type (sparing apical ballooning) has been more
      frequently described. We report the case of a 26-year-old man admitted with
      gastrointestinal symptoms, whose clinical presentation for a stress-related
      cardiomyopathy, which usually presents with cardiopulmonary symptoms, was rather
      atypical. The cardiac assessment including echocardiography and cardiac magnetic
      resonance imaging (MRI) demonstrated a dilated cardiomyopathy, whereas coronary
      angiography showed the absence of atherosclerotic disease. The abdominal computed
      tomography (CT) scan revealed a left adrenal mass, and elevated urinary
      catecholamine levels were highly suggestive of a pheochromocytoma. Prompt medical
      and surgical treatments were instituted. During the left adrenalectomy the
      patient suffered from brief electromechanical dissociation requiring aggressive
      resuscitation. Postoperative course was unremarkable. Reverse Takotsubo heart
      failure is a recently recognized syndrome and a systematic review of the
      literature of 10 cases of pheochromocytoma-induced inverted Takotsubo is
      presented in the present article. 

PMID- 20154634
TI  - Intractable spasm of saphenous vein conduits after coronary artery bypass grafts.

PMID- 20154635
TI  - Rapid carvedilol up-titration in hospitalized patients with left ventricular
      systolic dysfunction--data from the Carvedilol in Hospital: Up-titration Limits
      after Acute Patients Admission registry.
AB  - BACKGROUND AND OBJECTIVE: The safety of rapid carvedilol up-titration in patients
      with depressed left ventricular ejection fraction (LVEF) is unknown. The aim of
      the present work was to assess whether carvedilol can be used safely and rapidly
      up-titrated before hospital discharge in patients with left ventricular systolic
      dysfunction, with or without heart failure symptoms. METHODS: We studied 611
      patients with LVEF less than 0.4 in whom carvedilol was used during hospital
      admission. RESULTS: Mean age was 66 years, 23% were women and 372 had symptoms of
      heart failure. Carvedilol was initiated 3 days after admission (median); 594
      patients (97%) were discharged alive, 27 (5%) without beta-blockers. Carvedilol
      up-titration during admission was performed in 65%. The mean time of up-titration
      was 1 week, with a mean increase of 16 mg/day. The discharge dose was higher in
      younger patients and in those weighing more than 70 kg. Only 30 patients (5%)
      were re-admitted during the first month after discharge. At the end of follow-up
      (mean 2.3 years), 497 patients were alive and transplant-free (81%). Carvedilol
      mean daily dose at the end of follow-up was 32.4 +/- 22.2 mg and was related to
      the discharge dose. The absence of beta-blocker treatment at discharge was the
      most important independent predictor of long-term mortality (hazard ratio 3.1,
      95% confidence interval 1.5-6.2, P = 0.002). CONCLUSION: Carvedilol up-titration
      is well tolerated in patients hospitalized with depressed LVEF, with or without
      heart failure, with a high compliance rate at discharge and in the long term.

PMID- 20154636
TI  - Constrictive pericarditis as a late sequela of streptococcal pneumonia: 
      diagnostic role of cardiovascular magnetic resonance.

PMID- 20154637
TI  - Estrogen and progestogen use in postmenopausal women: 2010 position statement of
      The North American Menopause Society.
AB  - OBJECTIVE: To update for both clinicians and the lay public the evidence-based
      position statement published by The North American Menopause Society (NAMS) in
      July 2008 regarding its recommendations for menopausal hormone therapy (HT) for
      postmenopausal women, with consideration for the therapeutic benefit-risk ratio
      at various times through menopause and beyond. METHODS: An Advisory Panel of
      clinicians and researchers expert in the field of women's health was enlisted to
      review the July 2008 NAMS position statement, evaluate new evidence through an
      evidence-based analysis, and reach consensus on recommendations. The Panel' s
      recommendations were reviewed and approved by the NAMS Board of Trustees as an
      official NAMS position statement. Also participating in the review process were
      other interested organizations who then endorsed the document. RESULTS: Current
      evidence supports a consensus regarding the role of HT in postmenopausal women,
      when potential therapeutic benefits and risks around the time of menopause are
      considered. This paper lists all these areas along with explanatory comments.
      Areas that vary from the 2008 position statement are noted. A suggested reading
      list of key references published since the last statement is also provided.
      CONCLUSIONS: Recent data support the initiation of HT around the time of
      menopause to treat menopause-related symptoms; to treat or reduce the risk of
      certain disorders, such as osteoporosis or fractures in select postmenopausal
      women; or both. The benefit-risk ratio for menopausal HT is favorable for women
      who initiate HT close to menopause but decreases in older women and with time
      since menopause in previously untreated women.

PMID- 20154638
TI  - The value of I-131 SPECT in the detection of recurrent differentiated thyroid
      cancer.
AB  - AIM: The aim of this study is to assess the additional value of radioiodine-131
      (I-131) single-photon emission computed tomography (SPECT) to whole-body
      scintigraphy (WBS) in the detection of recurrent differentiated thyroid cancer.
      MATERIALS AND METHODS: Eighty-seven consecutive patients with differentiated
      thyroid cancer, who had undergone a diagnostic SPECT WBS study, were included. In
      all patients, posttreatment scans, computed tomography scanning or
      ultrasonography were used to assess positive results, whereas follow-up was used
      in patients with a negative scan result. General data, such as primary tumor,
      histology and biochemical parameters were also gathered. RESULTS: In this study
      cohort, nine positive diagnostic WBS were found compared with 31 positive SPECT
      scans. In eight of the nine (89%) positive WBS, recurrent thyroid cancer was
      found at the same location on the SPECT scan. In 56 patients SPECT and WBS were
      negative. Moreover, eight patients with a positive SPECT study had a serum
      thyroglobulin level less than 1 microg/l, which, in our hospital, was the cut-off
      level for treatment. On the basis of the serum thyroglobulin measurements and the
      WBS, 9% of the patients would not have been treated. CONCLUSION: I-131 SPECT of
      the head and neck region and chest has a complementary role for planar imaging in
      the follow-up of patients treated for differentiated thyroid cancer. Therefore,
      its use in addition to WBS is strongly recommended in clinical practice.

PMID- 20154639
TI  - Thrombotic disease in critically ill children.
AB  - OBJECTIVES: To summarize a) epidemiology of arterial and venous thromboembolism,
      pulmonary embolism, and deep venous thrombosis in children; b) the risk factors
      for thrombosis in the pediatric intensive care unit; c) diagnostic techniques for
      arterial/venous thromboembolism; and d) the current recommendations for
      management and prevention of thromboembolic disease in critically ill children.
      DATA SOURCE: Literature review, using National Library of Medicine PubMed and the
      following terms: arterial, venous thromboembolism; deep venous thrombosis;
      pulmonary embolism; thrombosis; as well as citations of interest from these
      articles. STUDY SELECTION: Both pediatric and adult literature addressing
      thrombotic disease were reviewed. DATA EXTRACTION AND SYNTHESIS: Articles were
      chosen for more extensive discussion when containing prospective studies,
      guidelines for practice, or data in critically ill patients. When data in
      children were unavailable, applicable data in adults were referenced. Due to the
      paucity of data in critically ill children, available adult and pediatric data
      were combined with institutional experience to provide suggestions for current
      practice and future inquiry. CONCLUSIONS: Increasing awareness regarding the
      recognition and current approaches to management and prevention of thromboembolic
      disease in children is needed among pediatric intensivists, so outcome of these
      life-threatening processes might be improved.

PMID- 20154640
TI  - Very important pharmacogene summary: thiopurine S-methyltransferase.

PMID- 20154641
TI  - Live imaging of Drosophila melanogaster embryonic hemocyte migrations.
AB  - Many studies address cell migration using in vitro methods, whereas the
      physiologically relevant environment is that of the organism itself. Here we
      present a protocol for the mounting of Drosophila melanogaster embryos and
      subsequent live imaging of fluorescently labeled hemocytes, the embryonic
      macrophages of this organism. Using the Gal4-uas system we drive the expression
      of a variety of genetically encoded, fluorescently tagged markers in hemocytes to
      follow their developmental dispersal throughout the embryo. Following collection
      of embryos at the desired stage of development, the outer chorion is removed and
      the embryos are then mounted in halocarbon oil between a hydrophobic, gas
      permeable membrane and a glass coverslip for live imaging. In addition to gross
      migratory parameters such as speed and directionality, higher resolution imaging
      coupled with the use of fluorescent reporters of F-actin and microtubules can
      provide more detailed information concerning the dynamics of these cytoskeletal
      components.

PMID- 20154642
TI  - A functional role for the p62-ERK1 axis in the control of energy homeostasis and
      adipogenesis.
AB  - In vivo genetic inactivation of the signalling adapter p62 leads to mature-onset
      obesity and insulin resistance, which correlate with reduced energy expenditure
      (EE) and increased adipogenesis, without alterations in feeding or locomotor
      functions. Enhanced extracellular signal-regulated kinase (ERK) activity in
      adipose tissue from p62-knockout (p62(-/-)) mice, and differentiating
      fibroblasts, suggested an important role for this kinase in the metabolic
      alterations of p62(-/-) mice. Here, we show that genetic inactivation of ERK1 in
      p62(-/-) mice reverses their increased adiposity and adipogenesis, lower EE and
      insulin resistance. These results establish genetically that p62 is a crucial
      regulator of ERK1 in metabolism.

PMID- 20154643
TI  - The spectacular landscape of chromatin and ncRNAs under the Tico sunlight.
AB  - The biannual Abcam meeting on Chromatin: Structure & Function held last November
      covered many aspects of chromatin regulation in health and disease. Important
      discussion points were the dynamic aspects of chromatin and the ever-increasing
      involvement of non-coding RNAs in chromatin and epigenetic mechanisms.

PMID- 20154644
TI  - Protein synthesis meets ABC ATPases: new roles for Rli1/ABCE1.

PMID- 20154645
TI  - Silencing in trans: position matters in fission yeast.

PMID- 20154647
TI  - Calcium channel blocker therapy in black hypertensive patients.

PMID- 20154649
TI  - Angiotensin II-type 2 receptor: emerging target for cardiovascular protection.

PMID- 20154650
TI  - The burden of obstructive sleep apnea along with masked hypertension on elastic
      properties.

PMID- 20154651
TI  - Is nondipping harmful in normotensive, healthy subjects?

PMID- 20154652
TI  - Hospitalization costs associated with hypertension as a secondary diagnosis.

PMID- 20154653
TI  - Sympathetic meta-analysis of adrenoceptor gene variants in hypertension.

PMID- 20154654
TI  - Role of oxidative stress in the pathogenesis of erythropoietin-induced
      hypertension.

PMID- 20154655
TI  - A novel antihypertensive effect of exenatide, a GLP-1 agonist.

PMID- 20154658
TI  - Retooling chemical probes.

PMID- 20154659
TI  - The art of the chemical probe.

PMID- 20154660
TI  - Rethinking screening.

PMID- 20154661
TI  - The (un)targeted cancer kinome.

PMID- 20154662
TI  - Our choices from the recent literature.

PMID- 20154663
TI  - Phenotypic screening: Fishing for neuroactive compounds.

PMID- 20154664
TI  - Synthetic chemistry: An upfront investment.

PMID- 20154665
TI  - Stem cells: Metabolism regulates differentiation.

PMID- 20154666
TI  - Turning enzymes ON with small molecules.
AB  - Drug discovery and chemical genetic efforts typically focus on the identification
      and design of inhibitors or loss-of-function probes as a means to perturb enzyme
      function. These tools are effective in determining the physiological consequence
      of ablating the activity of a specific enzyme. Remarkably, nearly a dozen
      examples of non-natural small molecules that activate enzyme catalysis have been
      identified within the past decade. In aggregate, these studies delineate four
      unique activation mechanisms that the small molecules exploit. These
      complementary gain-of-function probes offer a way to address the sufficiency of
      an enzyme to drive a particular cellular phenotype, and they also provide new
      opportunities for drug discovery. This review covers the identification and
      characterization of these unique small-molecule activators.

PMID- 20154668
TI  - The p110delta structure: mechanisms for selectivity and potency of new PI(3)K
      inhibitors.

PMID- 20154667
TI  - Garbled messages and corrupted translations.
AB  - Following transcription, genomic information begins a long journey toward
      translation of its nucleotide sequence into the amino acids of a protein. In
      eukaryotes, synthesized pre-mRNAs become processed to mature mRNAs by 5'-end
      capping, splicing, 3'-end cleavage and polyadenylation in the nucleus, before
      being scrutinized for premature stop codons. Each step requires high precision
      and control to ensure that an intact and readable message is exported to the
      cytoplasm before finally becoming translated. Two important aspects of these
      processes are accurately managed by ribonucleoprotein machineries-the spliceosome
      and the ribosome. Recently, several natural products targeting these
      macromolecular assemblies have been reported. For the first time in eukaryotes,
      these molecules allow chemical disruption and dissection of the sophisticated
      machinery that regulates post-transcriptional events. Beyond their great
      potential as bioprobes for investigating mRNA regulation and protein synthesis,
      these compounds also show promise in opening new therapeutic approaches.

PMID- 20154669
TI  - Aminoglycoside activity observed on single pre-translocation ribosome complexes.

PMID- 20154670
TI  - Chemical decay of an antibiotic inverts selection for resistance.

PMID- 20154671
TI  - Regulation of IL-9 expression by IL-25 signaling.
AB  - The physiological regulation of the expression of interleukin (IL)-9, a cytokine
      traditionally regarded as being T(H)2 associated, remains unclear. Here, we show
      that IL-9-expressing T cells generated in vitro in the presence of transforming
      growth factor-beta and IL-4 express high levels of mRNA for IL-17 receptor B (IL
      17RB), the receptor for IL-25. Treatment of these cells with IL-25 enhances IL-9
      expression in vitro. Moreover, transgenic and retroviral overexpression of IL
      17RB in T cells results in IL-25-induced IL-9 production that is IL-4
      independent. In vivo, the IL-25-IL-17RB pathway regulates IL-9 expression in
      allergic airway inflammation. Thus, IL-25 is a newly identified regulator of IL-9
      expression.

PMID- 20154672
TI  - An essential role for the transcription factor HEB in thymocyte survival, Tcra
      rearrangement and the development of natural killer T cells.
AB  - E proteins are basic helix-loop-helix transcription factors that regulate many
      key aspects of lymphocyte development. Thymocytes express multiple E proteins
      that are thought to provide cooperative and compensatory functions crucial for T
      cell differentiation. Contrary to that, we report here that the E protein HEB was
      uniquely required at the CD4(+)CD8(+) double-positive (DP) stage of T cell
      development. Thymocytes lacking HEB showed impaired survival, failed to make
      rearrangements of variable-alpha (V(alpha)) segments to distal joining-alpha
      (J(alpha)) segments in the gene encoding the T cell antigen receptor alpha-chain
      (Tcra) and had a profound, intrinsic block in the development of invariant
      natural killer T cells (iNKT cells) at their earliest progenitor stage. Thus, our
      results show that HEB is a specific and essential factor in T cell development
      and in the generation of the iNKT cell lineage, defining a unique role for HEB in
      the regulation of lymphocyte maturation.

PMID- 20154674
TI  - A recurrent 16p12.1 microdeletion supports a two-hit model for severe
      developmental delay.
AB  - We report the identification of a recurrent, 520-kb 16p12.1 microdeletion
      associated with childhood developmental delay. The microdeletion was detected in
      20 of 11,873 cases compared with 2 of 8,540 controls (P = 0.0009, OR = 7.2) and
      replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299
      controls (P = 0.028, OR = 2.5). Most deletions were inherited, with carrier
      parents likely to manifest neuropsychiatric phenotypes compared to non-carrier
      parents (P = 0.037, OR = 6). Probands were more likely to carry an additional
      large copy-number variant when compared to matched controls (10 of 42 cases, P =
      5.7 x 10(-5), OR = 6.6). The clinical features of individuals with two mutations
      were distinct from and/or more severe than those of individuals carrying only the
      co-occurring mutation. Our data support a two-hit model in which the 16p12.1
      microdeletion both predisposes to neuropsychiatric phenotypes as a single event
      and exacerbates neurodevelopmental phenotypes in association with other large
      deletions or duplications. Analysis of other microdeletions with variable
      expressivity indicates that this two-hit model might be more generally applicable
      to neuropsychiatric disease.

PMID- 20154676
TI  - Exploring the sequence determinants of amyloid structure using position-specific
      scoring matrices.
AB  - Protein aggregation results in beta-sheet-like assemblies that adopt either a
      variety of amorphous morphologies or ordered amyloid-like structures. These
      differences in structure also reflect biological differences; amyloid and
      amorphous beta-sheet aggregates have different chaperone affinities, accumulate
      in different cellular locations and are degraded by different mechanisms.
      Further, amyloid function depends entirely on a high intrinsic degree of order.
      Here we experimentally explored the sequence space of amyloid hexapeptides and
      used the derived data to build Waltz, a web-based tool that uses a position
      specific scoring matrix to determine amyloid-forming sequences. Waltz allows
      users to identify and better distinguish between amyloid sequences and amorphous
      beta-sheet aggregates and allowed us to identify amyloid-forming regions in
      functional amyloids.

PMID- 20154675
TI  - Germline mutations in TMEM127 confer susceptibility to pheochromocytoma.
AB  - Pheochromocytomas, which are catecholamine-secreting tumors of neural crest
      origin, are frequently hereditary. However, the molecular basis of the majority
      of these tumors is unknown. We identified the transmembrane-encoding gene TMEM127
      on chromosome 2q11 as a new pheochromocytoma susceptibility gene. In a cohort of
      103 samples, we detected truncating germline TMEM127 mutations in approximately
      30% of familial tumors and about 3% of sporadic-appearing pheochromocytomas
      without a known genetic cause. The wild-type allele was consistently deleted in
      tumor DNA, suggesting a classic mechanism of tumor suppressor gene inactivation.
      Pheochromocytomas with mutations in TMEM127 are transcriptionally related to
      tumors bearing NF1 mutations and, similarly, show hyperphosphorylation of
      mammalian target of rapamycin (mTOR) effector proteins. Accordingly, in vitro
      gain-of-function and loss-of-function analyses indicate that TMEM127 is a
      negative regulator of mTOR. TMEM127 dynamically associates with the endomembrane
      system and colocalizes with perinuclear (activated) mTOR, suggesting a
      subcompartmental-specific effect. Our studies identify TMEM127 as a tumor
      suppressor gene and validate the power of hereditary tumors to elucidate cancer
      pathogenesis.

PMID- 20154673
TI  - Common variants at 7p21 are associated with frontotemporal lobar degeneration
      with TDP-43 inclusions.
AB  - Frontotemporal lobar degeneration (FTLD) is the second most common cause of
      presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding
      protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial,
      resulting from mutations in GRN (which encodes progranulin). We assembled an
      international collaboration to identify susceptibility loci for FTLD-TDP through
      a genome-wide association study of 515 individuals with FTLD-TDP. We found that
      FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium
      block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide
      significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(
      11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association
      replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants
      may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants
      also contribute to genetic risk for FTLD-TDP in individuals with mutations in
      GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD
      TDP, suggesting an underlying pathogenic mechanism.

PMID- 20154677
TI  - Temporal pixel multiplexing for simultaneous high-speed, high-resolution imaging.
AB  - We introduce an imaging modality that, by offsetting pixel-exposure times during
      capture of a single image frame, embeds temporal information in each frame. This
      allows simultaneous acquisition of full-resolution images at native detector
      frame rates and high-speed image sequences at reduced resolution, without
      increasing bandwidth requirements. We demonstrate this method using macroscopic
      and microscopic examples, including imaging calcium transients in heart cells at
      250 Hz using a 10-Hz megapixel camera.

PMID- 20154678
TI  - Organelle-specific, rapid induction of molecular activities and membrane
      tethering.
AB  - Using new chemically inducible dimerization probes, we generated a system to
      rapidly target proteins to individual intracellular organelles. Using this
      system, we activated Ras GTPase at distinct intracellular locations and induced
      tethering of membranes from two organelles, endoplasmic reticulum and
      mitochondria. Innovative techniques to rapidly perturb molecular activities and
      organelle-organelle communications at precise locations and timing will provide
      powerful strategies to dissect spatiotemporally complex biological processes.

PMID- 20154679
TI  - Identification of the cell lineage at the origin of basal cell carcinoma.
AB  - For most types of cancers, the cell at the origin of tumour initiation is still
      unknown. Here, we used mouse genetics to identify cells at the origin of basal
      cell carcinoma (BCC), which is one of the most frequently occurring types of
      cancer in humans, and can result from the activation of the Hedgehog signalling
      pathway. Using mice conditionally expressing constitutively active Smoothened
      mutant (SmoM2), we activated Hedgehog signalling in different cellular
      compartments of the skin epidermis and determined in which compartments Hedgehog
      activation induces BCC formation. Activation of SmoM2 in hair follicle bulge stem
      cells and their transient amplifying progenies did not induce cancer formation,
      demonstrating that BCC does not originate from bulge stem cells, as previously
      thought. Using clonal analysis, we found that BCC arises from long-term resident
      progenitor cells of the interfollicular epidermis and the upper infundibulum. Our
      studies uncover the cells at the origin of BCC in mice and demonstrate that
      expression of differentiation markers in tumour cells is not necessarily
      predictive of the cancer initiating cells.

PMID- 20154680
TI  - TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript
      selective translational induction of Dab2 and ILEI.
AB  - Transforming growth factor-beta (TGF-beta) induces epithelial-mesenchymal
      transdifferentiation (EMT) accompanied by cellular differentiation and migration.
      Despite extensive transcriptomic profiling, the identification of TGF-beta
      inducible, EMT-specific genes has met with limited success. Here we identify a
      post-transcriptional pathway by which TGF-beta modulates the expression of EMT
      specific proteins and of EMT itself. We show that heterogeneous nuclear
      ribonucleoprotein E1 (hnRNP E1) binds a structural, 33-nucleotide TGF-beta
      activated translation (BAT) element in the 3' untranslated region of disabled-2
      (Dab2) and interleukin-like EMT inducer (ILEI) transcripts, and represses their
      translation. TGF-beta activation leads to phosphorylation at Ser 43 of hnRNP E1
      by protein kinase Bbeta/Akt2, inducing its release from the BAT element and
      translational activation of Dab2 and ILEI messenger RNAs. Modulation of hnRNP E1
      expression or its post-translational modification alters the TGF-beta-mediated
      reversal of translational silencing of the target transcripts and EMT. These
      results suggest the existence of a TGF-beta-inducible post-transcriptional
      regulon that controls EMT during the development and metastatic progression of
      tumours.

PMID- 20154681
TI  - The peroxisomal importomer constitutes a large and highly dynamic pore.
AB  - The peroxisomal protein import machinery differs fundamentally from known
      translocons (endoplasmic reticulum, mitochondria, chloroplasts, bacteria) as it
      allows membrane passage of folded, even oligomerized proteins. However, the
      mechanistic principles of protein translocation across the peroxisomal membrane
      remain unknown. There are various models that consider membrane invagination
      events, vesicle fusion or the existence of large import pores. Current data show
      that a proteinaceous peroxisomal importomer enables docking of the cytosolic
      cargo-loaded receptors, cargo translocation and receptor recycling. Remarkably,
      the cycling import receptor Pex5p changes its topology from a soluble cytosolic
      form to an integral membrane-bound form. According to the transient pore
      hypothesis, the membrane-bound receptor is proposed to form the core component of
      the peroxisomal import pore. Here, we demonstrate that the membrane-associated
      import receptor Pex5p together with its docking partner Pex14p forms a gated ion
      conducting channel which can be opened to a diameter of about 9 nm by the
      cytosolic receptor-cargo complex. The newly identified pore shows striking
      dynamics, as expected for an import machinery translocating proteins of variable
      sizes.

PMID- 20154682
TI  - Regulation of neuronal activity by Cav3-Kv4 channel signaling complexes.
AB  - Kv4 low voltage-activated A-type potassium channels are widely expressed in
      excitable cells, where they control action potential firing, dendritic activity
      and synaptic integration. Kv4 channels exist as a complex that includes K(+)
      channel-interacting proteins (KChIPs), which contain calcium-binding domains and
      therefore have the potential to confer calcium dependence on the Kv4 channel. We
      found that T-type calcium channels and Kv4 channels form a signaling complex in
      rat that efficiently couples calcium influx to KChIP3 to modulate Kv4 function.
      This interaction was critical for allowing Kv4 channels to function in the
      subthreshold membrane potential range to regulate neuronal firing properties. The
      widespread expression of these channels and accessory proteins indicates that the
      Cav3-Kv4 signaling complex is important for the function of a wide range of
      electrically excitable cells.

PMID- 20154683
TI  - Active flight increases the gain of visual motion processing in Drosophila.
AB  - We developed a technique for performing whole-cell patch-clamp recordings from
      genetically identified neurons in behaving Drosophila. We focused on the
      properties of visual interneurons during tethered flight, but this technique
      generalizes to different cell types and behaviors. We found that the peak-to-peak
      responses of a class of visual motion-processing interneurons, the vertical
      system visual neurons (VS cells), doubled when flies were flying compared with
      when they were at rest. Thus, the gain of the VS cells is not fixed, but is
      instead behaviorally flexible and changes with locomotor state. Using voltage
      clamp, we found that the passive membrane resistance of VS cells was reduced
      during flight, suggesting that the elevated gain was a result of increased
      synaptic drive from upstream motion-sensitive inputs. The ability to perform
      patch-clamp recordings in behaving Drosophila promises to help unify the
      understanding of behavior at the gene, cell and circuit levels.

PMID- 20154684
TI  - CXCR2-positive neutrophils are essential for cuprizone-induced demyelination:
      relevance to multiple sclerosis.
AB  - Multiple sclerosis is an inflammatory demyelinating disorder of the CNS. Recent
      studies have suggested diverse mechanisms as underlying demyelination, including
      a subset of lesions induced by an interaction between metabolic insult to
      oligodendrocytes and inflammatory mediators. For mice of susceptible strains,
      cuprizone feeding results in oligodendrocyte cell loss and demyelination of the
      corpus callosum. Remyelination ensues and has been extensively studied. Cuprizone
      induced demyelination remains incompletely characterized. We found that mice
      lacking the type 2 CXC chemokine receptor (CXCR2) were relatively resistant to
      cuprizone-induced demyelination and that circulating CXCR2-positive neutrophils
      were important for cuprizone-induced demyelination. Our findings support a two
      hit process of cuprizone-induced demyelination, supporting the idea that multiple
      sclerosis pathogenesis features extensive oligodendrocyte cell loss. These data
      suggest that cuprizone-induced demyelination is useful for modeling certain
      aspects of multiple sclerosis pathogenesis.

PMID- 20154685
TI  - Graphene nanomesh.
AB  - Graphene has significant potential for application in electronics, but cannot be
      used for effective field-effect transistors operating at room temperature because
      it is a semimetal with a zero bandgap. Processing graphene sheets into
      nanoribbons with widths of less than 10 nm can open up a bandgap that is large
      enough for room-temperature transistor operation, but nanoribbon devices often
      have low driving currents or transconductances. Moreover, practical devices and
      circuits will require the production of dense arrays of ordered nanoribbons,
      which remains a significant challenge. Here, we report the production of a new
      graphene nanostructure--which we call a graphene nanomesh--that can open up a
      bandgap in a large sheet of graphene to create a semiconducting thin film. The
      nanomeshes are prepared using block copolymer lithography and can have variable
      periodicities and neck widths as low as 5 nm. Graphene nanomesh field-effect
      transistors can support currents nearly 100 times greater than individual
      graphene nanoribbon devices, and the on-off ratio, which is comparable with the
      values achieved in individual nanoribbon devices, can be tuned by varying the
      neck width. The block copolymer lithography approach used to make the nanomesh
      devices is intrinsically scalable and could allow for the rational design and
      fabrication of graphene-based devices and circuits with standard semiconductor
      processing.

PMID- 20154686
TI  - High-speed atomic force microscopy shows dynamic molecular processes in
      photoactivated bacteriorhodopsin.
AB  - Dynamic changes in protein conformation in response to external stimuli are
      important in biological processes, but it has proved difficult to directly
      visualize such structural changes under physiological conditions. Here, we show
      that high-speed atomic force microscopy can be used to visualize dynamic changes
      in stimulated proteins. High-resolution movies of a light-driven proton pump,
      bacteriorhodopsin, reveal that, upon illumination, a cytoplasmic portion of each
      bacteriorhodopsin monomer is brought into contact with adjacent trimers. The
      bacteriorhodopsin-bacteriorhodopsin interaction in the transiently formed
      assembly engenders both positive and negative cooperative effects in the decay
      kinetics as the initial bacteriorhodopsin recovers and, as a consequence, the
      turnover rate of the photocycle is maintained constant, on average, irrespective
      of the light intensity. These results confirm that high-resolution visualization
      is a powerful approach for studying elaborate biomolecular processes under
      realistic conditions.

PMID- 20154688
TI  - Cold welding of ultrathin gold nanowires.
AB  - The welding of metals at the nanoscale is likely to have an important role in the
      bottom-up fabrication of electrical and mechanical nanodevices. Existing welding
      techniques use local heating, requiring precise control of the heating mechanism
      and introducing the possibility of damage. The welding of metals without heating
      (or cold welding) has been demonstrated, but only at macroscopic length scales
      and under large applied pressures. Here, we demonstrate that single-crystalline
      gold nanowires with diameters between 3 and 10 nm can be cold-welded together
      within seconds by mechanical contact alone, and under relatively low applied
      pressures. High-resolution transmission electron microscopy and in situ
      measurements reveal that the welds are nearly perfect, with the same crystal
      orientation, strength and electrical conductivity as the rest of the nanowire.
      The high quality of the welds is attributed to the nanoscale sample dimensions,
      oriented-attachment mechanisms and mechanically assisted fast surface-atom
      diffusion. Welds are also demonstrated between gold and silver, and silver and
      silver, indicating that the technique may be generally applicable.

PMID- 20154687
TI  - A diamond nanowire single-photon source.
AB  - The development of a robust light source that emits one photon at a time will
      allow new technologies such as secure communication through quantum cryptography.
      Devices based on fluorescent dye molecules, quantum dots and carbon nanotubes
      have been demonstrated, but none has combined a high single-photon flux with
      stable, room-temperature operation. Luminescent centres in diamond have recently
      emerged as a stable alternative, and, in the case of nitrogen-vacancy centres,
      offer spin quantum bits with optical readout. However, these luminescent centres
      in bulk diamond crystals have the disadvantage of low photon out-coupling. Here,
      we demonstrate a single-photon source composed of a nitrogen-vacancy centre in a
      diamond nanowire, which produces ten times greater flux than bulk diamond
      devices, while using ten times less power. This result enables a new class of
      devices for photonic and quantum information processing based on nanostructured
      diamond, and could have a broader impact in nanoelectromechanical systems,
      sensing and scanning probe microscopy.

PMID- 20154689
TI  - Organic semiconductors: What makes the spin relax?

PMID- 20154690
TI  - Multiferroics: A whirlwind of opportunities.

PMID- 20154691
TI  - A homologous series of structures on the surface of SrTiO3(110).
AB  - Strontium titanate is seeing increasing interest in fields ranging from thin-film
      growth to water-splitting catalysis and electronic devices. Although the surface
      structure and chemistry are of vital importance to many of these applications,
      theories about the driving forces vary widely. We report here a solution to the 3
      x 1 SrTiO(3)(110) surface structure obtained through transmission electron
      diffraction and direct methods, and confirmed through density functional theory
      calculations and scanning tunnelling microscopy images and simulations,
      consisting of rings of six or eight corner-sharing TiO(4) tetrahedra. Further, by
      changing the number of tetrahedra per ring, a homologous series of n x 1 (n > or
      = 2) surface reconstructions is formed. Calculations show that the lower members
      of the series (n < or = 6) are thermodynamically stable and the structures agree
      with scanning tunnelling microscopy images. Although the surface energy of a
      crystal is usually thought to determine the structure and stoichiometry, we
      demonstrate that the opposite can occur. The n x 1 reconstructions are
      sufficiently close in energy for the stoichiometry in the near-surface region to
      determine which reconstruction is formed. Our results indicate that the rules of
      inorganic coordination chemistry apply to oxide surfaces, with concepts such as
      homologous series and intergrowths as valid at the surface as they are in the
      bulk.

PMID- 20154692
TI  - Enhanced absorption and carrier collection in Si wire arrays for photovoltaic
      applications.
AB  - Si wire arrays are a promising architecture for solar-energy-harvesting
      applications, and may offer a mechanically flexible alternative to Si wafers for
      photovoltaics. To achieve competitive conversion efficiencies, the wires must
      absorb sunlight over a broad range of wavelengths and incidence angles, despite
      occupying only a modest fraction of the array's volume. Here, we show that arrays
      having less than 5% areal fraction of wires can achieve up to 96% peak
      absorption, and that they can absorb up to 85% of day-integrated, above-bandgap
      direct sunlight. In fact, these arrays show enhanced near-infrared absorption,
      which allows their overall sunlight absorption to exceed the ray-optics light
      trapping absorption limit for an equivalent volume of randomly textured planar
      Si, over a broad range of incidence angles. We furthermore demonstrate that the
      light absorbed by Si wire arrays can be collected with a peak external quantum
      efficiency of 0.89, and that they show broadband, near-unity internal quantum
      efficiency for carrier collection through a radial semiconductor/liquid junction
      at the surface of each wire. The observed absorption enhancement and collection
      efficiency enable a cell geometry that not only uses 1/100th the material of
      traditional wafer-based devices, but also may offer increased photovoltaic
      efficiency owing to an effective optical concentration of up to 20 times.

PMID- 20154693
TI  - Isotope effect in spin response of pi-conjugated polymer films and devices.
AB  - Recent advances in organic spin response include long polaron spin-coherence
      times measured by optically detected magnetic resonance (ODMR), substantive room
      temperature magnetoelectroluminescence and magnetoconductance obtained in organic
      light-emitting diodes (OLEDs) and spin-polarized carrier injection from
      ferromagnetic electrodes in organic spin valves (OSVs). Although the hyperfine
      interaction (HFI) has been foreseen to have an important role in organic spin
      response, no clear experimental evidence has been reported so far. Using the
      chemical versatility advantage of the organics, we studied and compared spin
      responses in films, OLED and OSV devices based on pi-conjugated polymers made of
      protonated, H-, and deuterated, D-hydrogen having a weaker HFI strength. We
      demonstrate that the HFI does indeed have a crucial role in all three spin
      responses. OLED films based on the D-polymers show substantially narrower magneto
      electroluminescence and ODMR responses, and as a result of the longer spin
      diffusion obtained, OSV devices based on D-polymers show a substantially larger
      magnetoresistance.

PMID- 20154694
TI  - Insulating interlocked ferroelectric and structural antiphase domain walls in
      multiferroic YMnO3.
AB  - Hexagonal YMnO(3) shows a unique improper ferroelectricity induced by structural
      trimerization. Extensive research on this system is primarily due to its
      candidacy for ferroelectric memory as well as the intriguing coexistence of
      ferroelectricity and magnetism. Despite this research, the true ferroelectric
      domain structure and its relationship with structural domains have never been
      revealed. Using transmission electron microscopy and conductive atomic force
      microscopy, we observed an intriguing conductive 'cloverleaf' pattern of six
      domains emerging from one point--all distinctly characterized by polarization
      orientation and structural antiphase relationships. In addition, we discovered
      that the ferroelectric domain walls and structural antiphase boundaries are
      mutually locked and this strong locking results in incomplete poling even when
      large electric fields are applied. Furthermore, the locked walls are found to be
      insulating, which seems consistent with the surprising result that the
      ferroelectric state is more conducting than the paraelectric state. These
      fascinating results reveal the rich physics of the hexagonal system with a truly
      semiconducting bandgap where structural trimerization, ferroelectricity,
      magnetism and charge conduction are intricately coupled.

PMID- 20154695
TI  - Pharmacological correction of a defect in PPAR-gamma signaling ameliorates
      disease severity in Cftr-deficient mice.
AB  - Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator (encoded by Cftr) that impair its role as an apical
      chloride channel that supports bicarbonate transport. Individuals with cystic
      fibrosis show retained, thickened mucus that plugs airways and obstructs luminal
      organs as well as numerous other abnormalities that include inflammation of
      affected organs, alterations in lipid metabolism and insulin resistance. Here we
      show that colonic epithelial cells and whole lung tissue from Cftr-deficient mice
      show a defect in peroxisome proliferator-activated receptor-gamma (PPAR-gamma,
      encoded by Pparg) function that contributes to a pathological program of gene
      expression. Lipidomic analysis of colonic epithelial cells suggests that this
      defect results in part from reduced amounts of the endogenous PPAR-gamma ligand
      15-keto-prostaglandin E(2) (15-keto-PGE(2)). Treatment of Cftr-deficient mice
      with the synthetic PPAR-gamma ligand rosiglitazone partially normalizes the
      altered gene expression pattern associated with Cftr deficiency and reduces
      disease severity. Rosiglitazone has no effect on chloride secretion in the colon,
      but it increases expression of the genes encoding carbonic anhydrases 4 and 2
      (Car4 and Car2), increases bicarbonate secretion and reduces mucus retention.
      These studies reveal a reversible defect in PPAR-gamma signaling in Cftr
      deficient cells that can be pharmacologically corrected to ameliorate the
      severity of the cystic fibrosis phenotype in mice.

PMID- 20154696
TI  - Innate immune lectins kill bacteria expressing blood group antigen.
AB  - The expression of ABO(H) blood group antigens causes deletion of cells that
      generate self-specific antibodies to these antigens but this deletion limits
      adaptive immunity toward pathogens bearing cognate blood group antigens. To
      explore potential defense mechanisms against such pathogens, given these
      limitations in adaptive immunity, we screened for innate proteins that could
      recognize human blood group antigens. Here we report that two innate immune
      lectins, galectin-4 (Gal-4) and Gal-8, which are expressed in the intestinal
      tract, recognize and kill human blood group antigen-expressing Escherichia coli
      while failing to alter the viability of other E. coli strains or other Gram
      negative or Gram-positive organisms both in vitro and in vivo. The killing
      activity of both Gal-4 and Gal-8 is mediated by their C-terminal domains, occurs
      rapidly and independently of complement and is accompanied by disruption of
      membrane integrity. These results demonstrate that innate defense lectins can
      provide immunity against pathogens that express blood group-like antigens on
      their surface.

PMID- 20154697
TI  - An oncogene-tumor suppressor cascade drives metastatic prostate cancer by
      coordinately activating Ras and nuclear factor-kappaB.
AB  - Metastasis is responsible for the majority of prostate cancer-related deaths;
      however, little is known about the molecular mechanisms that underlie this
      process. Here we identify an oncogene-tumor suppressor cascade that promotes
      prostate cancer growth and metastasis by coordinately activating the small GTPase
      Ras and nuclear factor-kappaB (NF-kappaB). Specifically, we show that loss of the
      Ras GTPase-activating protein (RasGAP) gene DAB2IP induces metastatic prostate
      cancer in an orthotopic mouse tumor model. Notably, DAB2IP functions as a
      signaling scaffold that coordinately regulates Ras and NF-kappaB through distinct
      domains to promote tumor growth and metastasis, respectively. DAB2IP is
      suppressed in human prostate cancer, where its expression inversely correlates
      with tumor grade and predicts prognosis. Moreover, we report that epigenetic
      silencing of DAB2IP is a key mechanism by which the polycomb-group protein
      histone-lysine N-methyltransferase EZH2 activates Ras and NF-kappaB and triggers
      metastasis. These studies define the mechanism by which two major pathways can be
      simultaneously activated in metastatic prostate cancer and establish EZH2 as a
      driver of metastasis.

PMID- 20154700
TI  - Vasectomy by epithelial curettage without suture or cautery: a pilot study in
      humans.
AB  - Curettage of the epithelium of the vas deferens might be a safe and effective
      method of male sterilization. We conducted a pilot study of vasectomy by
      epithelial curettage with a novel microcurette called the Vas-X in 12 normal men
      requesting elective sterilization. Seminal fluid analysis was obtained monthly
      after the procedure for 6 months. Pain was assessed by questionnaire. Three
      months after the procedure, all men attained sperm concentrations of less than
      0.2 million sperm per mL, and seven were azoospermic. Post-procedural pain was
      minimal. Nine men ultimately achieved and maintained azoospermia; however, 4 to 6
      months after the procedure, sperm concentrations increased in three of the 12
      subjects, necessitating repeat vasectomy. Microscopic examination of the vas
      deferens from these failures revealed re-canalization. Vasectomy by epithelial
      curettage can result in effective sterilization; however, 1/4 of the subjects
      were not effectively sterilized by the procedure due to re-canalization of the
      vas deferens. Epithelial curettage will require further refinement to determine
      if it is a viable form of vasectomy.

PMID- 20154699
TI  - Androgens and male aging: Current evidence of safety and efficacy.
AB  - Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone
      and muscle strength, bear a close resemblance to features of hypogonadism in
      younger men. The statistical decline of serum testosterone in aging men is
      solidly documented. It has been presumed that the above features of aging are
      related to the concurrent decline of androgens, and that correction of the lower
      than-normal circulating levels of testosterone will lead to improvement of
      symptoms of aging. But in essence, the pivotal question whether the age-related
      decline of testosterone must be viewed as hypogonadism, in the best case reversed
      by testosterone treatment, has not been definitively resolved. Studies in elderly
      men with lower-than-normal testosterone report improvement of features of the
      metabolic syndrome, bone mineral density, of mood and of sexual functioning. But
      as yet there is no definitive proof of the beneficial effects of restoring
      testosterone levels to normal in elderly men on clinical parameters. Few of these
      studies meet as yet rigorous standards of scientific enquiry: double-blind,
      placebo-controlled design of the study. The above applies also to the assessment
      of safety of testosterone administration to elderly men. There is so far no
      convincing evidence that testosterone is a main factor in the development of
      prostate cancer in elderly men and guidelines for monitoring the development of
      prostate disease have been developed. It is of note that there are presently no
      long-term safety data with regard to the prostate. Polycythemia is another
      potential complication of testosterone treatment. It is dose dependent and can be
      managed with dose adjustment.

PMID- 20154701
TI  - Metacaspases are caspases. Doubt no more.

PMID- 20154702
TI  - RIP1's function in NF-kappaB activation: from master actor to onlooker.

PMID- 20154704
TI  - Mechanism of error-free and semitargeted mutagenic bypass of an aromatic amine
      lesion by Y-family polymerase Dpo4.
AB  - The aromatic amine carcinogen 2-aminofluorene (AF) forms covalent adducts with
      DNA, predominantly with guanine at the C8 position. Such lesions are bypassed by
      Y-family polymerases such as Dpo4 via error-free and error-prone mechanisms. We
      show that Dpo4 catalyzes elongation from a correct 3'-terminal cytosine opposite
      [AF]G in a nonrepetitive template sequence with low efficiency. This extension
      leads to cognate full-length product, as well as mis-elongated products
      containing base mutations and deletions. Crystal structures of the Dpo4 ternary
      complex, with the 3'-terminal primer cytosine base opposite [AF]G in the anti
      conformation and with the AF moiety positioned in the major groove, reveal both
      accurate and misalignment-mediated mutagenic extension pathways. The mutagenic
      template-primer-dNTP arrangement is promoted by interactions between the
      polymerase and the bulky lesion rather than by a base pair-stabilized
      misaligment. Further extension leads to semitargeted mutations via this proposed
      polymerase-guided mechanism.

PMID- 20154703
TI  - CD24: from A to Z.
AB  - As a testament to the importance of CD24, researchers with diverse interests,
      including adaptive immunity, inflammation, autoimmune diseases and cancer, have
      encountered CD24. CD24 is overexpressed in many cancers and appears oncogenic. In
      the adaptive immune response, CD24 is a redundant costimulatory molecule in
      costimulation-rich lymphoid organs but is essential in selected target organs
      tested, such as brain and skin. More recent studies suggest it may have a role in
      discriminating danger and pathogen-associated molecular patterns by dendritic
      cells. The biology of CD24 is intriguing but poorly understood. Here we summarize
      the major findings associated with CD24 to stimulate new ideas for further
      research that may reveal the underlying link among the diverse processes mediated
      by CD24.

PMID- 20154705
TI  - A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via
      homologous recombination.
AB  - Double-stranded DNA breaks (DSBs) induce a phosphorylation-mediated signaling
      cascade, but the role of phosphatases in this pathway remains unclear. Here we
      show that human protein phosphatase 4 (PP4) dephosphorylates replication protein
      A (RPA) subunit RPA2, regulating its role in the DSB response. PP4R2, a
      regulatory subunit of PP4, mediates the DNA damage-dependent association between
      RPA2 and the PP4C catalytic subunit. PP4 efficiently dephosphorylates phospho
      RPA2 in vitro, and silencing PP4R2 in cells alters the kinetics and pattern of
      RPA2 phosphorylation. Depletion of PP4R2 impedes homologous recombination (HR)
      via inefficient loading of the essential HR factor RAD51, causing an extended G2
      M checkpoint and hypersensitivity to DNA damage. Cells expressing phosphomimetic
      RPA2 mutants have a comparable phenotype, suggesting that PP4-mediated
      dephosphorylation of RPA2 is necessary for an efficient DNA-damage response.
      These observations provide new insight into the role and regulation of RPA
      phosphorylation in HR-mediated repair.

PMID- 20154706
TI  - The structure of the catalytic subunit FANCL of the Fanconi anemia core complex.
AB  - The Fanconi anemia (FA) pathway is activated in response to DNA damage, leading
      to monoubiquitination of the substrates FANCI and FANCD2 by the FA core complex.
      Here we report the crystal structure of FANCL, the catalytic subunit of the FA
      core complex, at 3.2 A. The structure reveals an architecture fundamentally
      different from previous sequence-based predictions. The molecule is composed of
      an N-terminal E2-like fold, which we term the ELF domain, a novel double-RWD
      (DRWD) domain, and a C-terminal really interesting new gene (RING) domain
      predicted to facilitate E2 binding. Binding assays show that the DRWD domain, but
      not the ELF domain, is responsible for substrate binding.

PMID- 20154707
TI  - Munc13 C2B domain is an activity-dependent Ca2+ regulator of synaptic exocytosis.
AB  - Munc13 is a multidomain protein present in presynaptic active zones that mediates
      the priming and plasticity of synaptic vesicle exocytosis, but the mechanisms
      involved remain unclear. Here we use biophysical, biochemical and
      electrophysiological approaches to show that the central C(2)B domain of Munc13
      functions as a Ca(2+) regulator of short-term synaptic plasticity. The crystal
      structure of the C(2)B domain revealed an unusual Ca(2+)-binding site with an
      amphipathic alpha-helix. This configuration confers onto the C(2)B domain unique
      Ca(2+)-dependent phospholipid-binding properties that favor
      phosphatidylinositolphosphates. A mutation that inactivated Ca(2+)-dependent
      phospholipid binding to the C(2)B domain did not alter neurotransmitter release
      evoked by isolated action potentials, but it did depress release evoked by action
      potential trains. In contrast, a mutation that increased Ca(2+)-dependent
      phosphatidylinositolbisphosphate binding to the C(2)B domain enhanced release
      evoked by isolated action potentials and by action-potential trains. Our data
      suggest that, during repeated action potentials, Ca(2+) and
      phosphatidylinositolphosphate binding to the Munc13 C(2)B domain potentiate
      synaptic vesicle exocytosis, thereby offsetting synaptic depression induced by
      vesicle depletion.

PMID- 20154708
TI  - Mediator head module structure and functional interactions.
AB  - We used single-particle electron microscopy to characterize the structure and
      subunit organization of the Mediator Head module that controls Mediator-RNA
      polymerase II (RNAPII) and Mediator-promoter interactions. The Head module adopts
      several conformations differing in the position of a movable jaw formed by the
      Med18-Med20 subcomplex. We also characterized, by structural, biochemical and
      genetic means, the interactions of the Head module with TATA-binding protein
      (TBP) and RNAPII subunits Rpb4 and Rpb7. TBP binds near the Med18-Med20
      attachment point and stabilizes an open conformation of the Head module. Rpb4 and
      Rpb7 bind between the Head jaws, establishing contacts essential for yeast-cell
      viability. These results, and consideration of the structure of the Mediator
      RNAPII holoenzyme, shed light on the stabilization of the pre-initiation complex
      by Mediator and suggest how Mediator might influence initiation by modulating
      polymerase conformation and interaction with promoter DNA.

PMID- 20154709
TI  - The structures of the anti-tuberculosis antibiotics viomycin and capreomycin
      bound to the 70S ribosome.
AB  - Viomycin and capreomycin belong to the tuberactinomycin family of antibiotics,
      which are among the most effective antibiotics against multidrug-resistant
      tuberculosis. Here we present two crystal structures of the 70S ribosome in
      complex with three tRNAs and bound to either viomycin or capreomycin at 3.3- and
      3.5-A resolution, respectively. Both antibiotics bind to the same site on the
      ribosome, which lies at the interface between helix 44 of the small ribosomal
      subunit and helix 69 of the large ribosomal subunit. The structures of these
      complexes suggest that the tuberactinomycins inhibit translocation by stabilizing
      the tRNA in the A site in the pretranslocation state. In addition, these
      structures show that the tuberactinomycins bind adjacent to the binding sites for
      the paromomycin and hygromycin B antibiotics, which may enable the development of
      new derivatives of tuberactinomycins that are effective against drug-resistant
      strains.

PMID- 20154710
TI  - The novel squamosamide derivative FLZ enhances BDNF/TrkB/CREB signaling and
      inhibits neuronal apoptosis in APP/PS1 mice.
AB  - AIM: The aim of this study was to study the effects of compound FLZ, a novel
      cyclic derivative of squamosamide from Annona glabra, on brain-derived
      neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response
      element-binding protein (CREB) signaling and neuronal apoptosis in the
      hippocampus of the amyloid precursor protein (APP)/presenilin-1 (PS1) double
      transgenic mice. METHODS: APP/PS1 mice at the age of 5 months and age-matched
      wild-type mice (WT) were intragastrically administered FLZ (150 mg/kg) or vehicle
      [0.05% carboxymethyl cellulose sodium (CMC-Na)] daily for 20 weeks. The levels of
      BDNF in the hippocampus of WT and APP/PS1 mice were then measured by
      immunohistochemistry and Western blot analysis. Neuronal apoptosis in mouse
      hippocampus was detected by Nissl staining. Expression of NGF, NT3, pTrkB
      (Tyr515)/TrkB, pAkt (Ser473)/Akt, pERK/ERK, pCREB (Ser133)/CREB, Bcl-2/Bax, and
      active caspase-3 fragment/caspase-3 in the hippocampus of WT and APP/PS1 mice was
      detected by Western blot analysis. RESULTS: Compared with vehicle-treated APP/PS1
      mice, FLZ (150 mg/kg) significantly increased BDNF and NT3 expression in the
      hippocampus of APP/PS1 mice. In addition, FLZ promoted BDNF high-affinity
      receptor TrkB phosphorylation and activated its downstream ERK, thus increasing
      phosphorylation of CREB at Ser133 in the hippocampus of APP/PS1 mice. Moreover,
      FLZ showed neuroprotective effects on neuronal apoptosis by increasing the Bcl
      2/Bax ratio and decreasing the active caspase-3 fragment/caspase-3 ratio in the
      hippocampus of APP/PS1 mice. CONCLUSION: FLZ exerted neuroprotection at least
      partly through enhancing the BDNF/TrkB/CREB pathway and inhibiting neuronal
      apoptosis in APP/PS1 mice, which suggests that FLZ can be explored as a potential
      therapeutic agent in long-term Alzheimer's disease therapy.

PMID- 20154711
TI  - Glycogen synthase kinase-3beta regulates astrocytic differentiation of U87-MG
      human glioblastoma cells.
AB  - AIM: To evaluate the role of glycogen synthase kinase-3beta (GSK-3beta) in the
      induced differentiation of human glioblastoma cells. METHODS: Cell proliferation
      was determined by bromodeoxyuridine (BrdU) incorporation assay. The protein level
      of p-GSK-3beta, GSK-3beta, glial fibrillary acidic protein (GFAP) and
      proliferating cell nuclear antigen (PCNA) were determined using Western blots.
      The overexpression of mutant GSK-3beta was analyzed by immunocytochemistry.
      RESULTS: The biotoxin cholera toxin is capable of inducing differentiation of U87
      MG human glioblastoma cells, which is characterized by morphological changes to
      astrocytic phenotype, increase in differentiation marker protein GFAP and
      decrease in proliferation. GSK-3beta activation is induced during this
      differentiation. Small interfering RNA against GSK-3beta suppresses the induced
      differentiation in U87-MG cells. Conversely, overexpression of a constitutively
      active form of human GSK-3beta (pcDNA3-GSK-3beta-S9A) mutant leads to
      differentiation of U87-MG cells. CONCLUSION: Our findings suggest that GSK-3beta
      plays an important role in astrocytic differentiation of human glioblastoma cells
      and may be a novel therapeutic target in the malignant tumor.

PMID- 20154712
TI  - Oligomannurarate sulfate blocks tumor growth by inhibiting NF-kappaB activation.
AB  - AIM: JG3, a novel marine-derived oligosaccharide, significantly inhibits
      angiogenesis and tumor metastasis by blocking heparanase activity. It also
      arrests tumor growth, an effect that is not fully explained by its anti
      heparanase activity. Here we sought to identify the mechanisms underlying JG3
      mediated inhibition of tumor growth. METHODS: Heparanase expression was assessed
      by RT-PCR and Western blotting. NF-kappaB activation status was determined using
      immunofluorescence, Western blotting, DNA-binding and transcription-activity
      assays. The effect of JG3 on upstream components of the NF-kappaB pathway and on
      selected transcription factors were monitored by Western blotting. The antitumor
      effect of JG3 and its relation to NF-kappaB activation were evaluated using four
      different tumor xenograft models. RESULTS: We found that JG3 effectively
      inhibited NF-kappaB activation independent of heparanase expression. Our results
      indicate that JG3 inactivated NF-kappaB by interfering with the activation of
      upstream components of the NF-kappaB pathway without generally affecting the
      nuclear translocation of transcription factors. Further, in vivo studies
      demonstrated that JG3 effectively arrested the growth of tumors derived from cell
      lines in which NF-kappaB was constitutively active (BEL-7402 liver carcinoma and
      MDA-MB-435s breast carcinoma), but did not affect the growth of tumors derived
      from NF-kappaB-negative cell lines (SGC-7901 gastric cancer and HO-8910 ovarian
      carcinoma). CONCLUSION: Our data indicate that NF-kappaB mediates the JG3-induced
      arrest of tumor growth. These results define a new mechanism of action of JG3 and
      highlight the potential for JG3 as a promising lead molecule in cancer therapy.

PMID- 20154713
TI  - Protective action of tetramethylpyrazine phosphate against dilated cardiomyopathy
      in cTnT(R141W) transgenic mice.
AB  - AIM: Dilated cardiomyopathy (DCM) is the most common cause of heart failure, and
      pharmacological intervention is not currently available. Here we investigate the
      effect of tetramethylpyrazine phosphate (TMPP) on the progression of DCM in the
      cTnT(R141W) transgenic mouse model. METHODS: The cTnT(R141W) transgenic mice aged
      2 months were divided into model group and TMPP group, whereas age-matched
      nontransgenic mice were used as wild-type control. TMPP 45 mg.kg(-1).d(-1) was
      administered for 7 months. Following assessment of cardiac function by
      echocardiography, cardiac tissues were prepared for histology and electron
      microscopy. Levels of molecular markers for cardiomyocyte hypertrophy and
      fibrosis were detected by RT-PCR. Expression of structural proteins of the
      sarcomere and intercalated disc was determined by Western blot. RESULTS: TMPP
      significantly prevented cardiac dilatation and dysfunction with the development
      of DCM, and decreased mortality by 54%. TMPP decreased HW/BW ratios and
      expression of hypertrophic markers BNP and ACTA1, as well as reduced interstitial
      collagen deposition and expression of profibrotic markers Col1a1 and Col3a1. TMPP
      attenuated ultrastructural disruption caused by cTnT(R141W) expression and
      decreased expression of structural proteins myotilin and E-cadherin which were up
      regulated in the cTnT(R141W) heart. Moreover, TMPP reduced the mRNA expression of
      Calm1 and Camk2b in the cTnT(R141W) heart. CONCLUSION: Our results suggest that
      TMPP could be a promising drug for prevention and treatment of DCM.

PMID- 20154714
TI  - Knockdown of FoxM1 by siRNA interference decreases cell proliferation, induces
      cell cycle arrest and inhibits cell invasion in MHCC-97H cells in vitro.
AB  - AIM: To investigate the effects of small interfering RNA (siRNA) knockdown of
      forkhead box M1 (FoxM1) on the proliferation and invasion capacities of human
      hepatocellular carcinoma MHCC-97H cells in vitro. METHODS: The expression levels
      of FoxM1 in human hepatocellular carcinoma samples, adjacent non-hepatocellular
      carcinoma liver samples and MHCC-97 cell lines were detected by RT-PCR and
      Western blotting. FoxM1 siRNA was transfected into MHCC-97H cells with
      Lipofectamine 2000. Cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, and cell cycle analysis was performed by
      flow cytometry. Protein expression levels were evaluated by Western blotting.
      Anchorage-independent growth and the invasive potency of MHCC-97H cells were
      measured by soft agar colony formation and a transwell cell invasion assay,
      respectively. RESULTS: FoxM1 was over-expressed in hepatocellular carcinoma
      samples compared to adjacent non-hepatocellular carcinoma liver samples. FoxM1
      siRNA was successfully transfected into MHCC-97H cells, resulting in the
      significant inhibition of FoxM1 mRNA and protein expression. Down-regulation of
      FoxM1 inhibited cell proliferation, caused cell cycle arrest, and decreased
      invasion of MHCC-97H cells. Compared with control and mock groups, the FoxM1
      siRNA transfected cells showed decreased protein expressions of cyclin B1 and
      cyclin D1, whereas p27 protein expression was increased. Down-regulation of FoxM1
      reduced the expression of matrix metalloproteinase-2 (MMP-2) and urokinase
      plasminogen activator (uPA). CONCLUSION: FoxM1 is functionally involved in
      hepatocellular carcinoma cell proliferation and invasion and is a potential
      target for hepatocellular carcinoma therapy.

PMID- 20154715
TI  - L-carnitine and taurine synergistically inhibit the proliferation and
      osteoblastic differentiation of vascular smooth muscle cells.
AB  - AIM: To investigate the synergistic action of L-carnitine (LC) and taurine (TAU)
      on the proliferation and osteoblastic differentiation of vascular smooth muscle
      cells (VSMCs). METHODS: DNA and protein synthesis of VSMCs were assessed using
      scintillation counting. Alkaline phosphatase (ALP) activity and calcium content
      were determined to investigate the effects of LC and TAU on the osteoblastic
      differentiation and mineralization of VSMCs. TAU uptake by VSMCs was assayed. RNA
      interference was used to down-regulate the expression of the TAU transporter
      (TAUT) in rat VSMCs. RESULTS: LC and TAU synergistically inhibited the
      proliferation and beta-glycerophosphate (beta-GP)-induced osteoblastic
      differentiation of VSMCs as evidenced by the decreased [(3)H]thymidine
      incorporation, ALP activity and calcium deposition. Furthermore, LC stimulated
      the TAU uptake and TAUT expression in VSMCs. Suppression of TAUT with short
      hairpin RNA (shRNA) abolished the synergistic action of LC and TAU in VSMCs.
      CONCLUSION: The synergistic inhibitory action of LC and TAU on the proliferation
      and osteoblastic differentiation of VSMCs is attributable to the up-regulation of
      TAUT expression and TAU uptake by LC.

PMID- 20154717
TI  - PI4KIIalpha is a novel regulator of tumor growth by its action on angiogenesis
      and HIF-1alpha regulation.
AB  - Tumor growth is the orchestration of various oncogenes and tumor suppressors, and
      the regulation of these genes offers a rational therapeutic approach to cancer
      treatment. In this study, we found a new regulator of tumor growth,
      phosphatidylinositol 4-kinase type IIalpha (PI4KIIalpha), the mechanism of which
      is involved in angiogenesis and hypoxia-inducible factor HIF-1alpha regulation.
      Results obtained from a human cancer tissue microarray showed that PI4KIIalpha
      protein expression increases markedly in seven types of cancers compared with
      normal tissues. Suppression of PI4KIIalpha leads to retarded tumor growth in nude
      mice. Downregulation of PI4KIIalpha in cancer cells eliminates tumor cell-induced
      endothelial cell tubulogenesis and migration, and results in impaired
      angiogenesis. Further investigation showed that PI4KIIalpha can directly regulate
      HIF-1alpha expression and that the expression of these two proteins is correlated
      in vivo. At the same time, downregulation of PI4KIIalpha markedly reduces HER-2
      autophosphorylation, and PI4KIIalpha specifically triggers HIF-1alpha
      accumulation through a phosphatidylinositol 3-kinase (PI3K)- and extracellular
      signal-regulated protein kinase (ERK)-dependent pathway, suggesting that
      PI4KIIalpha may regulate HIF-1alpha through the HER-2/PI3K, ERK cascade. In
      summary, we discovered a pivotal role for PI4KIIalpha in the regulation of tumor
      growth. Our results shed new light on understanding the novel functions of
      PI4KIIalpha in cancer and suggest that PI4KIIalpha may be a promising specific
      target for tumor therapy.

PMID- 20154716
TI  - Transforming growth factor-beta1 upregulates the expression of CXC chemokine
      receptor 4 (CXCR4) in human breast cancer MCF-7 cells.
AB  - AIM: To investigate whether rhTGF-beta1 or a recombinant vector encoding a fusion
      protein comprising an extracellular domain of TGF-beta receptor II and an IgG Fc
      fragment) affects the regulation of CXC chemokine receptor 4 (CXCR4) expression
      in MCF-7 human breast cancer cells. METHODS: MCF-7 breast cancer cells were
      treated with rhTGF-beta1 or transfected with a recombinant vector, pIRES2-EGFP
      TbetaRII-Fc. Expression of CXCR4 in these cells was then analyzed at the mRNA and
      protein levels by quantitative RT-PCR and flow cytometry assay, respectively. A
      transwell assay was used to measure the chemotactic response of these cells to
      SDF-1alpha. RESULTS: CXCR4 mRNA and protein expression were upregulated in TGF
      beta1-treated MCF-7 cells. These cells also demonstrated an enhanced chemotactic
      response to SDF-1alpha. In MCF-7 cells transiently transfected with pIRES2-EGFP
      TbetaRII-Fc, a fusion protein named TbetaRII-Fc (approximately 41 kDa) was
      produced and secreted. In these transfected cells, there was a reduction in CXCR4
      expression and in the SDF-1alpha-mediated chemotactic response. CONCLUSION: TGF
      beta1 upregulated CXCR4 expression in MCF-7 cells, which subsequently enhanced
      the SDF-1alpha-induced chemotactic response. The results suggest a link between
      TGF-beta1 and CXCR4 expression in MCF-7 human breast cancer cells, which may be
      one of the mechanisms of TGF-beta1-mediated enhancement of metastatic potential
      in breast cancer cells.

PMID- 20154718
TI  - Loss of poly(ADP-ribose) polymerase-2 leads to rapid development of spontaneous T
      cell lymphomas in p53-deficient mice.
AB  - Poly(ADP-ribose) polymerase-2 (Parp-2) belongs to a family of enzymes that
      catalyse poly(ADP-ribosyl)ation of proteins. Parp-2 deficiency in mice (Parp-2(-/
      )) results in reduced thymic cellularity associated with increased apoptosis in
      thymocytes, defining Parp-2 as an important mediator of T-cell survival during
      thymopoiesis. To determine whether there is a link between Parp-2 and the p53 DNA
      damage-dependent apoptotic response, we have generated Parp-2/p53-double-null
      mutant mice. We found that p53(-/-) backgrounds completely restored the survival
      and development of Parp-2(-/-) thymocytes. However, Parp-2-deficient thymocytes
      accumulated high levels of DNA double-strand breaks (DSB), independently of the
      p53 status, in line with a function of Parp-2 as a caretaker promoting genomic
      stability during thymocytes development. Although Parp-2(-/-) mice do not have
      spontaneous tumours, Parp-2 deficiency accelerated spontaneous tumour development
      in p53-null mice, mainly T-cell lymphomas. These data suggest a synergistic
      interaction between Parp-2 and p53 in tumour suppression through the role of Parp
      2 in DNA-damage response and genome integrity surveillance, and point to the
      potential importance of examining human tumours for the status of both genes.

PMID- 20154719
TI  - ASAP1 promotes tumor cell motility and invasiveness, stimulates metastasis
      formation in vivo, and correlates with poor survival in colorectal cancer
      patients.
AB  - We have previously performed an unbiased screen to identify genes whose
      expression is associated with the metastatic phenotype. Secondary screening of
      these genes using custom microarray chips identified ASAP1, a multi-domain
      adaptor protein with ADP-ribosylation factor-GAP activity, as being potentially
      involved in tumor progression. Here, we show that at least three different splice
      forms of ASAP1 are upregulated in rodent tumor models in a manner that correlates
      with metastatic potential. In human cancers, we found that ASAP1 expression is
      strongly upregulated in a variety of tumors in comparison with normal tissue and
      that this expression correlates with poor metastasis-free survival and prognosis
      in colorectal cancer patients. Using loss and gain of function approaches, we
      were able to show that ASAP1 promotes metastasis formation in vivo and stimulates
      tumor cell motility, invasiveness, and adhesiveness in vitro. Furthermore, we
      show that ASAP1 interacts with the metastasis-promoting protein h-prune and
      stimulates its phosphodiesterase activity. In addition, ASAP1 binds to the SH3
      domains of several proteins, including SLK with which it co-immunoprecipitates.
      These data support the notion that ASAP1 can contribute to the dissemination of a
      variety of tumor types and represent a potential target for cancer therapy.

PMID- 20154720
TI  - Notch-1 stimulates survival of lung adenocarcinoma cells during hypoxia by
      activating the IGF-1R pathway.
AB  - Hypoxic microenvironment supports cancer stem cell survival, causes poor response
      to anticancer therapy and tumor recurrence. Inhibition of Notch-1 signaling in
      adenocarcinoma of the lung (ACL) cells causes apoptosis specifically under
      hypoxia. Here, we found that Akt-1 activation is a key mediator of Notch-1 pro
      survival effects under hypoxia. Notch-1 activates Akt-1 through repression of
      phosphatase and tensin (PTEN) homolog expression and induction of the insulin
      like growth factor 1 receptor (IGF-1R). The latter seems to be the major
      determinant of Akt-1 stimulation, as Notch-1 signaling affects Akt-1 activation
      in PTEN(-/-) ACL cells. Both downregulation of insulin receptor substrate 1 (IRS
      1) and dominant-negative IGF-1R sensitized ACL cells to gamma-secretase inhibitor
      (GSI)-induced apoptosis. Conversely, overexpression of IGF-1R protected ACL cells
      from GSI toxicity. Inhibition of Notch-1 caused reduced IGF-1R expression,
      whereas forced Notch-1 expression yielded opposite effects. Chromatin
      immunoprecipitation experiments suggested Notch-1 direct regulation of the IGF-1R
      promoter. Experiments in which human ACL cells were injected in mice confirmed
      elevated and specific co-expression of Notch-1(IC), IGF-1R and pAkt-1 in hypoxic
      tumor areas. Our data provide a mechanistic explanation for Notch-1-mediated pro
      survival function in hypoxic ACL tumor microenvironment. The results identify
      additional targets that may synergize with Notch-1 inhibition for ACL treatment.

PMID- 20154721
TI  - NF2-deficient cells depend on the Rac1-canonical Wnt signaling pathway to promote
      the loss of contact inhibition of proliferation.
AB  - The neurofibromatosis type 2 (NF2) tumor suppressor gene encodes merlin, a
      membrane/cytoskeleton protein necessary for the maintenance of contact inhibition
      of growth in cells. Bi-allelic inactivation of NF2 is known to cause multiple
      cancers in both humans and mice. However, the mechanism through which merlin
      exerts its tumor-suppressive function remains obscure. In this report, we show
      that NF2 knockout mouse embryonic fibroblasts lost contact inhibition of cell
      proliferation and contained significantly increased canonical Wnt signaling.
      Inhibition of Rac1, the activity of which is inversely regulated by NF2, through
      the use of a dominant-negative mutant, small hairpin RNA or a small molecule
      inhibitor in NF2-deficient cells, was able to suppress elevated Wnt signals as
      shown by reduced activity of the T-cell factor 4 (TCF4) transcription factor.
      Dominant-negative TCF4 or Rac1 mutant, as well as a small molecule inhibition of
      Wnt, were able to curb NF2 deficiency-elicited cell proliferation at the
      confluent state. Thus, Rac1-mediated canonical Wnt signaling is essential for the
      loss of contact inhibition in NF2-deficient cells.

PMID- 20154722
TI  - Cyclin D1 is a direct transcriptional target of GATA3 in neuroblastoma tumor
      cells.
AB  - Almost all neuroblastoma tumors express excess levels of Cyclin D1 (CCND1)
      compared to normal tissues and other tumor types. Only a small percentage of
      these neuroblastoma tumors have high-level amplification of the Cyclin D1 gene.
      The other neuroblastoma tumors have equally high Cyclin D1 expression without
      amplification. Silencing of Cyclin D1 expression was previously found to trigger
      differentiation of neuroblastoma cells. Overexpression of Cyclin D1 is therefore
      one of the most frequent mechanisms with a postulated function in neuroblastoma
      pathogenesis. The cause for the Cyclin D1 overexpression is unknown. Here we show
      that Cyclin D1 overexpression results from transcriptional upregulation. To
      identify upstream regulators, we searched in mRNA profiles of neuroblastoma tumor
      series for transcription factors with expression patterns correlating to Cyclin
      D1. GATA3 most consistently correlated to Cyclin D1 in four independent data
      sets. We identified a highly conserved GATA3 binding site 27 bp upstream of the
      Cyclin D1 transcriptional start. Chromatin immune precipitation confirmed binding
      of GATA3 to the Cyclin D1 promoter. Overexpression of GATA3 induced Cyclin D1
      promoter activity, which decreased after site-directed mutagenesis of the GATA3
      binding site in the Cyclin D1 promoter. Silencing of GATA3 resulted in reduced
      Cyclin D1 promoter activity and reduced Cyclin D1 mRNA and protein levels.
      Moreover, GATA3 silencing caused differentiation that was similar to that caused
      by Cyclin D1 inhibition. These finding implicate GATA3 in Cyclin D1
      overexpression in neuroblastoma.

PMID- 20154723
TI  - An HDAC1-binding domain within FATS bridges p21 turnover to radiation-induced
      tumorigenesis.
AB  - There is a gap between the initial formation of cells carrying radiation-induced
      genetic damage and their contribution to cancer development. Herein, we reveal a
      previously uncharacterized gene FATS through a genome-wide approach and
      demonstrate its essential role in regulating the abundance of p21 in surveillance
      of genome integrity. A large exon coding the NH2-terminal domain of FATS, deleted
      in spontaneous mouse lymphomas, is much more frequently deleted in radiation
      induced mouse lymphomas. Its human counterpart is a fragile site gene at a
      previously identified loss of heterozygosity site. FATS is essential for
      maintaining steady-state level of p21 protein and sustaining DNA damage
      checkpoint. Furthermore, the NH2-terminal FATS physically interacts with histone
      deacetylase 1 (HDAC1) to enhance the acetylation of endogenous p21, leading to
      the stabilization of p21. Our results reveal a molecular linkage between p21
      abundance and radiation-induced carcinogenesis.

PMID- 20154724
TI  - Epidermal growth factor receptor regulates MET levels and invasiveness through
      hypoxia-inducible factor-1alpha in non-small cell lung cancer cells.
AB  - Recent studies have established that amplification of the MET proto-oncogene can
      cause resistance to epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs) in non-small cell lung cancer (NSCLC) cell lines with EGFR
      activating mutations. The role of non-amplified MET in EGFR-dependent signaling
      before TKI resistance, however, is not well understood. Using NSCLC cell lines
      and transgenic models, we demonstrate here that EGFR activation by either
      mutation or ligand binding increases MET gene expression and protein levels. Our
      analysis of 202 NSCLC patient specimens was consistent with these observations:
      levels of MET were significantly higher in NSCLC with EGFR mutations than in
      NSCLC with wild-type EGFR. EGFR regulation of MET levels in cell lines occurred
      through the hypoxia-inducible factor (HIF)-1alpha pathway in a hypoxia
      independent manner. This regulation was lost, however, after MET gene
      amplification or overexpression of a constitutively active form of HIF-1alpha.
      EGFR- and hypoxia-induced invasiveness of NSCLC cells, but not cell survival,
      were found to be MET dependent. These findings establish that, absent MET
      amplification, EGFR signaling can regulate MET levels through HIF-1alpha and that
      MET is a key downstream mediator of EGFR-induced invasiveness in EGFR-dependent
      NSCLC cells.

PMID- 20154725
TI  - Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate,
      the RECK tumor-suppressor protein through microRNAs.
AB  - Cancer cells show characteristic gene expression profiles. Recent studies support
      the potential importance of microRNA (miRNA) expression signatures as biomarkers
      and therapeutic targets. The membrane-anchored protease regulator RECK is
      downregulated in many cancers, and forced expression of RECK in tumor cells
      results in decreased malignancy in animal models. RECK is also essential for
      mammalian development. In this study, we found that RECK is a target of at least
      three groups of miRNAs (miR-15b/16, miR-21 and miR-372/373); that RECK mutants
      lacking the target sites for these miRNA show augmented tumor/metastasis
      suppressor activities; and that miR-372/373 are upregulated in response to
      hypoxia through HIF1alpha and TWIST1, whereas miR-21 is upregulated by RAS/ERK
      signaling. These data indicate that the hypoxia- and RAS-signaling pathways
      converge on RECK through miRNAs, cooperatively downregulating this tumor
      suppressor and thereby promoting malignant cell behavior.

PMID- 20154726
TI  - A potential tumor suppressor role for Hic1 in breast cancer through
      transcriptional repression of ephrin-A1.
AB  - The tumor suppressor gene hypermethylated in cancer 1 (HIC1), which encodes a
      transcriptional repressor, is epigenetically inactivated in various human
      cancers. In this study, we show that HIC1 is a direct transcriptional repressor
      of the gene encoding ephrin-A1, a cell surface ligand implicated in the
      pathogenesis of epithelial cancers. We also show that mouse embryos lacking both
      Hic1 alleles manifest developmental defects spatially associated with the
      misexpression of ephrin-A1, and that overexpression of ephrin-A1 is a feature of
      tumors arising in Hic1 heterozygous mice in which the remaining wild-type allele
      is epigenetically silenced. In breast cancer, we find that ephrin-A1 expression
      is common in vivo, but that in cell culture, expression of the EphA receptors is
      predominant. Restoration of HIC1 function in breast cancer cells leads to a
      reduction in tumor growth in vivo, an effect that can be partially rescued by co
      overexpression of ephrin-A1. Interestingly, overexpression of ephrin-A1 in vitro
      triggers downregulation of EphA2 and EphA4 levels, resulting in an expression
      pattern similar to that seen in vivo. We conclude that Hic1 spatially restricts
      ephrin-A1 expression in development, and that upregulated expression of ephrin-A1
      resulting from epigenetic silencing of HIC1 in cancer cells may be an important
      mechanism in epithelial malignancy.

PMID- 20154727
TI  - Identification of candidate tumour suppressor genes frequently methylated in
      renal cell carcinoma.
AB  - Promoter region hyermethylation and transcriptional silencing is a frequent cause
      of tumour suppressor gene (TSG) inactivation in many types of human cancers.
      Functional epigenetic studies, in which gene expression is induced by treatment
      with demethylating agents, may identify novel genes with tumour-specific
      methylation. We used high-density gene expression microarrays in a functional
      epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty-eight genes
      were then selected for analysis of promoter methylation status in cell lines and
      primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and
      COL15A1) showed frequent (>30% of RCC tested) tumour-specific promoter region
      methylation. Hypermethylation was associated with transcriptional silencing. Re
      expression of BNC1, CST6, RPRM and SFRP1 suppressed the growth of RCC cell lines
      and RNA interference knock-down of BNC1, SFRP1 and COL14A1 increased the growth
      of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer
      prognosis independent of tumour size, stage or grade. The identification of these
      epigenetically inactivated candidate RCC TSGs can provide insights into renal
      tumourigenesis and a basis for developing novel therapies and biomarkers for
      prognosis and detection.

PMID- 20154728
TI  - Inhibition of cancer cell proliferation and metastasis by insulin receptor
      downregulation.
AB  - Insulin receptor (IR) and the type I IGF receptor (IGF1R) are structurally and
      functionally related. The function of IGF1R in cancer has been well documented
      and anti-IGF1R strategies to treat cancer have shown initial positive results.
      However, the role of IR in tumor biology, independent of IGF1R, is less clear. To
      address this issue, short hairpin RNA (shRNA) was used to specifically
      downregulate IR in two cancer cell lines, LCC6 and T47D. Cells with reduced IR
      showed reduced insulin-stimulated Akt activation, without affecting IGF1R
      activation. Cells with reduced IR formed fewer colonies in anchorage-independent
      conditions. LCC6 IR shRNA xenograft tumors in mice had reduced growth,
      angiogenesis and lymphangiogensis when compared with LCC6 wild-type cells.
      Accordingly, LCC6 IR shRNA clones produced less hypoxia-inducible factor-1alpha,
      vascular endothelial growth factor (VEGF)-A and VEGF-D. Furthermore, LCC6 IR
      shRNA cells formed fewer pulmonary metastases when compared with LCC6 wild-type
      cells. Using in vivo luciferase imaging, we have shown that LCC6 IR shRNA cells
      have less seeding and colonization potential in the lung and liver of mice than
      LCC6 cells. In conclusion, downregulation of IR inhibited cancer cell
      proliferation, angiogenesis, lymphangiogenesis and metastasis. Our data argue
      that IR should also be targeted in cancer therapy.

PMID- 20154729
TI  - In vivo imaging of haematopoietic cells emerging from the mouse aortic
      endothelium.
AB  - Haematopoietic stem cells (HSCs), responsible for blood production in the adult
      mouse, are first detected in the dorsal aorta starting at embryonic day 10.5
      (E10.5). Immunohistological analysis of fixed embryo sections has revealed the
      presence of haematopoietic cell clusters attached to the aortic endothelium where
      HSCs might localize. The origin of HSCs has long been controversial and several
      candidates of the direct HSC precursors have been proposed (for review see ref.
      7), including a specialized endothelial cell population with a haemogenic
      potential. Such cells have been described both in vitro in the embryonic stem
      cell (ESC) culture system and retrospectively in vivo by endothelial lineage
      tracing and conditional deletion experiments. Whether the transition from
      haemogenic endothelium to HSC actually occurs in the mouse embryonic aorta is
      still unclear and requires direct and real-time in vivo observation. To address
      this issue we used time-lapse confocal imaging and a new dissection procedure to
      visualize the deeply located aorta. Here we show the dynamic de novo emergence of
      phenotypically defined HSCs (Sca1(+), c-kit(+), CD41(+)) directly from ventral
      aortic haemogenic endothelial cells.

PMID- 20154730
TI  - Neurogenic radial glia in the outer subventricular zone of human neocortex.
AB  - Neurons in the developing rodent cortex are generated from radial glial cells
      that function as neural stem cells. These epithelial cells line the cerebral
      ventricles and generate intermediate progenitor cells that migrate into the
      subventricular zone (SVZ) and proliferate to increase neuronal number. The
      developing human SVZ has a massively expanded outer region (OSVZ) thought to
      contribute to cortical size and complexity. However, OSVZ progenitor cell types
      and their contribution to neurogenesis are not well understood. Here we show that
      large numbers of radial glia-like cells and intermediate progenitor cells
      populate the human OSVZ. We find that OSVZ radial glia-like cells have a long
      basal process but, surprisingly, are non-epithelial as they lack contact with the
      ventricular surface. Using real-time imaging and clonal analysis, we demonstrate
      that these cells can undergo proliferative divisions and self-renewing asymmetric
      divisions to generate neuronal progenitor cells that can proliferate further. We
      also show that inhibition of Notch signalling in OSVZ progenitor cells induces
      their neuronal differentiation. The establishment of non-ventricular radial glia
      like cells may have been a critical evolutionary advance underlying increased
      cortical size and complexity in the human brain.

PMID- 20154731
TI  - Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding
      ribosome.
AB  - The in vivo, genetically programmed incorporation of designer amino acids allows
      the properties of proteins to be tailored with molecular precision. The
      Methanococcus jannaschii tyrosyl-transfer-RNA synthetase-tRNA(CUA) (MjTyrRS
      tRNA(CUA)) and the Methanosarcina barkeri pyrrolysyl-tRNA synthetase-tRNA(CUA)
      (MbPylRS-tRNA(CUA)) orthogonal pairs have been evolved to incorporate a range of
      unnatural amino acids in response to the amber codon in Escherichia coli.
      However, the potential of synthetic genetic code expansion is generally limited
      to the low efficiency incorporation of a single type of unnatural amino acid at a
      time, because every triplet codon in the universal genetic code is used in
      encoding the synthesis of the proteome. To encode efficiently many distinct
      unnatural amino acids into proteins we require blank codons and mutually
      orthogonal aminoacyl-tRNA synthetase-tRNA pairs that recognize unnatural amino
      acids and decode the new codons. Here we synthetically evolve an orthogonal
      ribosome (ribo-Q1) that efficiently decodes a series of quadruplet codons and the
      amber codon, providing several blank codons on an orthogonal messenger RNA, which
      it specifically translates. By creating mutually orthogonal aminoacyl-tRNA
      synthetase-tRNA pairs and combining them with ribo-Q1 we direct the incorporation
      of distinct unnatural amino acids in response to two of the new blank codons on
      the orthogonal mRNA. Using this code, we genetically direct the formation of a
      specific, redox-insensitive, nanoscale protein cross-link by the bio-orthogonal
      cycloaddition of encoded azide- and alkyne-containing amino acids. Because the
      synthetase-tRNA pairs used have been evolved to incorporate numerous unnatural
      amino acids, it will be possible to encode more than 200 unnatural amino acid
      combinations using this approach. As ribo-Q1 independently decodes a series of
      quadruplet codons, this work provides foundational technologies for the encoded
      synthesis and synthetic evolution of unnatural polymers in cells.

PMID- 20154732
TI  - Blood stem cells emerge from aortic endothelium by a novel type of cell
      transition.
AB  - The ontogeny of haematopoietic stem cells (HSCs) during embryonic development is
      still highly debated, especially their possible lineage relationship to vascular
      endothelial cells. The first anatomical site from which cells with long-term HSC
      potential have been isolated is the aorta-gonad-mesonephros (AGM), more
      specifically the vicinity of the dorsal aortic floor. But although some authors
      have presented evidence that HSCs may arise directly from the aortic floor into
      the dorsal aortic lumen, others support the notion that HSCs first emerge within
      the underlying mesenchyme. Here we show by non-invasive, high-resolution imaging
      of live zebrafish embryos, that HSCs emerge directly from the aortic floor,
      through a stereotyped process that does not involve cell division but a strong
      bending then egress of single endothelial cells from the aortic ventral wall into
      the sub-aortic space, and their concomitant transformation into haematopoietic
      cells. The process is polarized not only in the dorso-ventral but also in the
      rostro-caudal versus medio-lateral direction, and depends on Runx1 expression: in
      Runx1-deficient embryos, the exit events are initially similar, but much rarer,
      and abort into violent death of the exiting cell. These results demonstrate that
      the aortic floor is haemogenic and that HSCs emerge from it into the sub-aortic
      space, not by asymmetric cell division but through a new type of cell behaviour,
      which we call an endothelial haematopoietic transition.

PMID- 20154733
TI  - Haematopoietic stem cells derive directly from aortic endothelium during
      development.
AB  - A major goal of regenerative medicine is to instruct formation of multipotent,
      tissue-specific stem cells from induced pluripotent stem cells (iPSCs) for cell
      replacement therapies. Generation of haematopoietic stem cells (HSCs) from iPSCs
      or embryonic stem cells (ESCs) is not currently possible, however, necessitating
      a better understanding of how HSCs normally arise during embryonic development.
      We previously showed that haematopoiesis occurs through four distinct waves
      during zebrafish development, with HSCs arising in the final wave in close
      association with the dorsal aorta. Recent reports have suggested that murine HSCs
      derive from haemogenic endothelial cells (ECs) lining the aortic floor.
      Additional in vitro studies have similarly indicated that the haematopoietic
      progeny of ESCs arise through intermediates with endothelial potential. Here we
      have used the unique strengths of the zebrafish embryo to image directly the
      generation of HSCs from the ventral wall of the dorsal aorta. Using combinations
      of fluorescent reporter transgenes, confocal time-lapse microscopy and flow
      cytometry, we have identified and isolated the stepwise intermediates as aortic
      haemogenic endothelium transitions to nascent HSCs. Finally, using a permanent
      lineage tracing strategy, we demonstrate that the HSCs generated from haemogenic
      endothelium are the lineal founders of the adult haematopoietic system.

PMID- 20154734
TI  - Organization of immunological memory by bone marrow stroma.
AB  - Immunological memory is a hallmark of the adaptive immune system. Plasma cells
      and memory B and T cells collectively provide protective immunity and effective
      secondary immune responses to invading pathogens. Here, we discuss how
      mesenchymal stromal cells regulate immunological memory by organizing defined
      numbers of dedicated survival niches for plasma cells and memory T cells in the
      bone marrow and also, to a lesser extent, in secondary lymphoid organs. An
      understanding of the biology of mesenchymal stromal cells and their interaction
      with cells of the immune system is key to fully understanding immunological
      memory.

PMID- 20154736
TI  - Monitoring the international use of unrelated donors for transplantation: the
      WMDA annual reports.
AB  - The World Marrow Donor Association Annual Reports describe the current status of
      the use of unrelated hematopoietic cell products worldwide. In 2008, almost 1.7
      million individuals were recruited into unrelated stem cell donor registries and
      almost 78 000 cord blood units were added to the inventory increasing the total
      number of available stem cell donors worldwide to over 14 million. In 2008, there
      were 10 481 adult stem cell donations (3221 BM and 7260 PBSC donations) provided
      from stem cell donor registries in 38 countries. In 2008, 3529 cord blood
      products were provided from 21 countries. Although the number of BM donations has
      been stable over the past 10 years, donations of PBSCs and umbilical cord blood
      are increasing.

PMID- 20154737
TI  - Attainment of at least a very good partial response after induction treatment is
      an important surrogate of longer survival for multiple myeloma.
AB  - The importance of achieving a very good partial response or better (>=VGPR) after
      induction treatment of myeloma has traditionally only been discussed in the
      context of high-dose therapy with auto-SCT (HDT/auto-SCT). Of late, the advent of
      novel agents for induction treatment has resulted in improved CR and VGPR rates,
      which are comparable with those observed with HDT/auto-SCT. We show that in an
      unselected group of 179 myeloma patients with diverse baseline characteristics,
      and treated with different modern induction regimens within a single institution,
      the attainment of >=VGPR with or without HDT/auto-ASCT represents a major
      surrogate marker of better clinical outcomes. On the basis of a 1-year landmark
      survival analysis, patients achieving >=VGPR enjoy a significantly longer PFS,
      which translated to a longer OS. Superseding the adverse effects of advanced age,
      high International Staging System (ISS) stage, adverse cytogenetics and
      independent of the transplant status, the attainment of >=VGPR emerged as the
      single most significant predictor of long-term survival on multivariate analysis.

PMID- 20154735
TI  - The regulation of IL-10 production by immune cells.
AB  - Interleukin-10 (IL-10), a cytokine with anti-inflammatory properties, has a
      central role in infection by limiting the immune response to pathogens and
      thereby preventing damage to the host. Recently, an increasing interest in how
      IL10 expression is regulated in different immune cells has revealed some of the
      molecular mechanisms involved at the levels of signal transduction, epigenetics,
      transcription factor binding and gene activation. Understanding the specific
      molecular events that regulate the production of IL-10 will help to answer the
      remaining questions that are important for the design of new strategies of immune
      intervention.

PMID- 20154738
TI  - Outcome of allo-SCT for women with MDS or AML occurring after breast cancer
      therapy.
AB  - Women with breast cancer who receive adjuvant therapy are at risk for developing
      therapy-related myelodysplastic syndrome (MDS) or AML (tMDS/AML). Patients with
      tMDS/AML are often referred for consideration of allogeneic hematopoietic SCT
      (HSCT). However, the outcomes of HSCT in such patients have not been well
      described. We report a retrospective study of all women who were treated with
      HSCT for MDS or AML at our institution between 1991 and 2008. We compared the
      transplantation outcomes for 24 women with a history of breast cancer with those
      for 271 women with de novo disease. Three-year OS and disease-free survival (DFS)
      for patients with a history of breast cancer were 41 and 45%, respectively. The
      cumulative incidences of tMDS/AML relapse and non-relapse mortality (NRM) were 38
      and 17%, respectively. Those outcomes were very similar to those of patients with
      de novo disease. In multivariable analyses, a history of breast cancer had no
      impact on OS, DFS, relapse or NRM. A significant proportion of women with
      tAML/MDS after breast cancer treatment experience DFS after HSCT, similar to that
      of patients with de novo MDS or AML. This justifies consideration of HSCT for
      selected patients in this setting.

PMID- 20154740
TI  - Nonpolarizing beam splitter designed by frustrated total internal reflection
      inside a glass cube: publisher's note.

PMID- 20154739
TI  - The role of allogeneic SCT in primary myelofibrosis: a British Society for Blood
      and Marrow Transplantation study.
AB  - Fifty-one patients with primary myelofibrosis (PMF) received allogeneic
      haematopoietic stem cell transplants from related (n=33) or unrelated (n=18)
      donors. Twenty-seven patients, 19-54 years old, were prepared with myeloablative
      regimens including CY plus BU (n=4) or TBI (n=23). Twenty-four patients, 40-64
      years old, received reduced-intensity conditioning (RIC) regimens. All RIC
      regimens contained fludarabine, combined with melphalan (n=19) or BU (n=5), and
      alemtuzumab or anti-thymocyte globulin (ATG) in the majority (n=19). Four
      patients (17%) in the RIC group had primary graft failure. Previous splenectomy
      reduced time to engraftment in the RIC group (13 versus 20 days; P=0.008). For MA
      and RIC groups, respectively, at 3 years, overall survival rates were 44 and 31%
      (P=0.67), progression-free survival 44 and 24% (P=0.87), and actuarial relapse
      rates 15 and 46% (P=0.06). Non-relapse mortality at 3 years was 41% for the
      myeloablative and 32% for the RIC group. Acute GVHD occurred in 29 and 38% of
      patients in the myeloablative and RIC groups, respectively. Extensive chronic
      GVHD developed in 30 and 35% of evaluable patients, respectively.

PMID- 20154741
TI  - Design of fused-silica rectangular transmission gratings for polarizing beam
      splitter based on modal method.
AB  - Examples of optimal designs for a fused-silica transmitted grating with high
      intensity tolerance are discussed. It has the potential of placing up to 99%
      incident polarized light in a single diffraction order. The modal method has been
      used to analyze the effective indices for TE and TM polarization propagating
      through the grating region, and the eigenvalue equation of the modal method is
      transformed to a new form. It is shown that the effective indices of the first
      two modes depend on the value of the period under Littrow mounting with filling
      factor f=0.5. The polarization properties of the polarizing beam splitter are
      analyzed by rigorous coupled-wave analysis (RCWA) at the wavelength of 1.064
      microm. The optimal design perfectly matches the RCWA simulation result.

PMID- 20154742
TI  - Data-nonintrusive photonics-based credit card verifier with a low false rejection
      rate.
AB  - We propose and experimentally demonstrate a noninvasive credit card verifier with
      a low false rejection rate (FRR). Our key idea is based on the use of three
      broadband light sources in our data-nonintrusive photonics-based credit card
      verifier structure, where spectral components of the embossed hologram images are
      registered as red, green, and blue. In this case, nine distinguishable variables
      are generated for a feed-forward neural network (FFNN). In addition, we
      investigate the center of mass of the image histogram projected onto the x axis
      (I(color)), making our system more tolerant of the intensity fluctuation of the
      light source. We also reduce the unwanted signals on each hologram image by
      simply dividing the hologram image into three zones and then calculating their
      corresponding I(color) values for red, green, and blue bands. With our proposed
      concepts, we implement our field test prototype in which three broadband white
      light light-emitting diodes (LEDs), a two-dimensional digital color camera, and a
      four-layer FFNN are used. Based on 249 genuine credit cards and 258 counterfeit
      credit cards, we find that the average of differences in I(color) values between
      genuine and counterfeit credit cards is improved by 1.5 times and up to 13.7
      times. In this case, we can effectively verify credit cards with a very low FRR
      of 0.79%.

PMID- 20154743
TI  - Super-resolution for flash ladar imagery.
AB  - Flash ladar systems are compact devices with high frame rates that hold promise
      for robotics applications, but these devices suffer from poor spatial resolution.
      This work develops a wavelet preprocessing stage to enhance registration of
      multiple frames and applies super-resolution to improve the resolution of flash
      ladar range imagery. The triangle orientation discrimination methodology was used
      for a subjective evaluation of the effectiveness of super-resolution for flash
      ladar. Results show statistically significant increases in the probability of
      target discrimination at all target ranges, as well as a reduction in subject
      response times for super-resolved imagery.

PMID- 20154744
TI  - Reliability of content-addressable data search in a defocused volume holographic
      data storage system.
AB  - We investigate for suitable methods that enable reliable content-addressable data
      search in a defocused volume holographic data storage system. Two techniques have
      been introduced and are shown to overcome the shortcomings of the known methods
      used to perform content searching in defocused holographic recording geometry. In
      effect, we remove the deterministic errors that result because of the presence of
      nonmatching database records, producing almost the same correlation scores as the
      true targeted correlation scores. Such deterministic errors give rise to
      erroneous search outcomes and reduce the speed advantage of the parallel
      holographic data search. We present experimental results and discuss the
      improvements offered by the two introduced methods in terms of storage density
      and measured correlation scores. Both the methods of modified-balanced and 25%
      sparse modulation coded data pages are found to produce good results, negating
      the undesired correlation characteristics.

PMID- 20154745
TI  - Simultaneous measurement of group refractive index and thickness of optical
      samples using optical coherence tomography.
AB  - Optical coherence tomography (OCT), based on a Michelson interferometer and
      utilizing low coherence light as the optical source, is a novel technique for the
      noninvasive imaging of optical scattering media. A simple OCT scheme based on a 3
      x 3 fiber coupler is presented for the simultaneous measurement of the refractive
      index and thickness of optical samples. The proposed system enables the
      refractive index and thickness to be determined without any prior knowledge of
      the sample parameters and is characterized by a simple and compact configuration,
      a straightforward measurement procedure, and a low cost. The feasibility of the
      proposed approach is demonstrated experimentally using BK7 and B270 optical glass
      samples.

PMID- 20154746
TI  - Vicarious calibration of satellite ocean color sensors at two coastal sites.
AB  - Regionally specific vicarious calibration coefficients for ocean color sensors
      have been computed for the visible bands using the normalized water leaving
      radiance L(wn) collected at sites in the northern Adriatic Sea and Baltic Proper.
      These coefficients are consistent with those found in oligotrophic waters for the
      Sea-viewing Wide Field-of-view Sensor (SeaWiFS) and Moderate Resolution Imaging
      Spectroradiometer (MODIS) . The extension of the vicarious calibration process to
      the near-infrared is investigated by taking advantage of the field data of
      aerosol optical thickness coincident with L(wn). Results further confirm the
      importance of accurately modeling and identifying the aerosol components in
      atmospheric correction schemes.

PMID- 20154747
TI  - Compact diode stack end pumped Nd:YAG amplifier using core doped ceramics.
AB  - We report on a compact Nd:YAG amplifier emitting a maximum pulse energy of 14 mJ.
      By amplifying a passively Q-switched oscillator (M(2)<1.2) a good beam quality of
      M(2) approximately 1.7 was achieved. The amplifier is diode pumped by an 8 bar
      diode stack of 800 W power and a nonimaging optic. This optic homogenizes the
      pump light and transfers it into a 5 mm diameter core doped rod with a centrally
      neodymium doped region of 3 mm and a samarium doped YAG cladding. We show that
      this cladding reduces parasitic effects in the laser rod compared to an undoped
      YAG cladding. Finally, we compare the compact amplifier with an amplifier, which
      is mode selectively pumped by a fiber coupled pump diode.

PMID- 20154748
TI  - Analytic solution for quasi-Lambertian radiation transfer.
AB  - An analytic solution is derived for radiation transfer between flat quasi
      Lambertian surfaces of arbitrary orientation, i.e., surfaces that radiate in a
      Lambertian fashion but within a numerical aperture smaller than unity. These
      formulas obviate the need for ray trace simulations and provide exact, physically
      transparent results. Illustrative examples that capture the salient features of
      the flux maps and the efficiency of flux transfer are presented for a few
      configurations of practical interest. There is also a fundamental reciprocity
      relation for quasi-Lambertian exchange, akin to the reciprocity theorem for fully
      Lambertian surfaces. Applications include optical fiber coupling, fiber-optic
      biomedical procedures, and solar concentrators.

PMID- 20154749
TI  - Simultaneous dispersion and dispersion-slope compensator based on a doubly
      sampled ultrahigh-channel-count fiber Bragg grating.
AB  - A simultaneous dispersion and dispersion-slope compensator based on a doubly
      sampled fiber Bragg grating (FBG) with 153 channels has been demonstrated, which
      is obtained by simultaneously chirping the period of the seed grating and the
      periods of the two sampling functions. These two sampling functions are optimized
      with the simulated annealing algorithm and the Gerchberg-Saxton iterative method.
      Moreover, the spectral inclination (in reflection) inherently due to the
      different magnitudes of the channel dispersion has been successfully equalized.

PMID- 20154750
TI  - Optical properties and electronic band structure of AgGaTe2 chalcopyrite
      semiconductor.
AB  - The optical properties of AgGaTe(2) chalcopyrite semiconductor are studied by
      optical absorption, spectroscopic ellipsometry (SE), and thermoreflectance (TR)
      spectroscopy. Optical absorption spectra suggest that AgGaTe(2) is a direct-gap
      semiconductor having a bandgap of approximately 1.2 eV at T=300 K. The
      pseudodielectric-function spectra of AgGaTe(2) are determined by SE in the range
      between E=1.2 and 5.2 eV for both states of polarization. These spectra reveal
      distinct structures at energies of the critical points in the Brillouin zone. The
      TR spectra are also measured in the E=1.0-5.3 eV ranges at T=20 K-300 K. The spin
      orbit and crystal-field splitting parameters of AgGaTe(2) are determined to be
      Delta(so)=0.70 eV and Delta(cr)=-0.23 eV, respectively.

PMID- 20154751
TI  - Equi-intensity distribution of optical reflectance in a fibrous turbid medium.
AB  - Light propagation in a fibrous anisotropic scattering medium is quite different
      from that in an isotropic medium. Both the anisotropic diffuse equation (ADE) and
      the continuous time random walk (CTRW) theory predict that the equi-intensity
      profiles of the surface reflectance have an elliptical shape in a fibrous turbid
      medium. In this study, we simulated the spatially resolved surface reflectance in
      a fibrous sample using a Monte Carlo model. A parametric equation was used to
      quantitatively characterize the geometric profiles of the reflectance patterns.
      The results indicated that the equi-intensity profiles of surface reflectance had
      elliptical shapes only when evaluated at distances far away from the incident
      point. The length ratio of the two orthogonal axes of the ellipse was not
      affected by the sample optical properties when the ratio of reduced scattering
      coefficients along the two axes is the same. But the relationship between the
      aforementioned two ratios was different from the predication of ADE theory. Only
      for fibers of small sizes did the fitted axes ratios approach the values
      predicted from the ADE theory.

PMID- 20154752
TI  - Synthetic aperture superresolved microscopy in digital lensless Fourier
      holography by time and angular multiplexing of the object information.
AB  - The resolving power of an imaging system in digital lensless Fourier holographic
      configuration is mainly limited by the numerical aperture of the experimental
      setup that is defined by both the restricted CCD size and the presence of a beam
      splitter cube in front of the CCD. We present a method capable of improving the
      resolution in such a system configuration based on synthetic aperture (SA)
      generation by using time-multiplexing tilted illumination onto the input object.
      Moreover, a priori knowledge about the imaged object allows customized SA shaping
      by the addition of elementary apertures only in the directions of interest.
      Experimental results are provided, showing agreement with theoretical predictions
      and demonstrating a resolution limit corresponding with a synthetic numerical
      aperture value of 0.45.

PMID- 20154753
TI  - Energy collection efficiency of holographic planar solar concentrators.
AB  - We analyze the energy collection properties of holographic planar concentrator
      systems. The effects of solar variation on daily and annual energy collection are
      evaluated. Hologram diffraction efficiency, polarization, crosstalk in cascaded
      elements, and constraints imposed by the radiance theorem, as well as solar
      illumination characteristics, are considered. A planar holographic solar
      concentrator configuration is designed and modeled to maximize energy collection
      efficiency during the course of a year without the need for tracking. Results
      indicated that nearly 50% of the available energy illuminating hologram areas can
      be collected by photovoltaic cells without the need of tracking.

PMID- 20154754
TI  - Diode laser frequency locking using Zeeman effect and feedback in temperature.
AB  - We demonstrate the stabilization of a laser diode frequency, using the circular
      dichroism of an alkali vapor and feeding back the correction signal to the
      temperature actuator of the junction. The conditions of operation and the
      performance of such a system are discussed.

PMID- 20154756
TI  - Spectral irradiance model for tungsten halogen lamps in 340-850 nm wavelength
      range.
AB  - We have developed a physical model for the spectral irradiance of 1 kW tungsten
      halogen incandescent lamps for the wavelength range 340-850 nm. The model
      consists of the Planck's radiation law, published values for the emissivity of
      tungsten, and a residual spectral correction function taking into account unknown
      factors of the lamp. The correction function was determined by measuring the
      spectra of a 1000 W, quartz-halogen, tungsten coiled filament (FEL) lamp at
      different temperatures. The new model was tested with lamps of types FEL and 1000
      W, 120 V quartz halogen (DXW). Comparisons with measurements of two national
      standards laboratories indicate that the model can account for the spectral
      irradiance values of lamps with an agreement better than 1% throughout the
      spectral region studied. We further demonstrate that the spectral irradiance of a
      lamp can be predicted with an expanded uncertainty of 2.6% if the color
      temperature and illuminance values for the lamp are known with expanded
      uncertainties of 20 K and 2%, respectively. In addition, it is suggested that the
      spectral irradiance may be derived from resistance measurements of the filament
      with lamp on and off.

PMID- 20154755
TI  - Direct image of surface-plasmon-coupled emission by leakage radiation microscopy.
AB  - Leakage radiation microscopy (LRM) is used to directly image surface-plasmon
      coupled emission (SPCE). When compared with the prism-based setup commonly used
      in SPCE research, LRM has the advantages of directly giving out the emitting
      direction without angle scanning, and the image generated of surface plasmon
      polariton (SPPs) propagation, which helps to understand the optical process of
      SPCE. LRM also can give a clearer SPCE image than that obtained by a prism-based
      setup. Based on the LRM, we find that the SPCE pattern and propagation of SPPs
      can be modified by the shape of PMMA films containing fluorescence molecules.

PMID- 20154757
TI  - High resolution imaging of patterned model biological membranes by localized
      surface plasmon microscopy.
AB  - We report on microscopic imaging of phospholipid membranes. To achieve nonlabel,
      noncontact, and high spatial resolution imaging of the membranes, we use
      optically excited localized surface plasmons as a virtual measurement probe to
      obtain the local refractive index. This enables significantly higher lateral
      resolution of approximately 170 nm. We reveal that the developed microscope has
      the capability of observing lipid bilayers with thickness of 3.0 nm deposited
      into the gaps in a patterned lipid bilayer with thickness of 4.6 nm. We find that
      the thickness resolution against the deposited lipid bilayer is approximately
      0.33 nm.

PMID- 20154758
TI  - Field-induced guiding optical devices made from electro-optic polymers.
AB  - Field-induced guiding (FIG) has been known for several decades. Many advanced
      optical FIG devices (light modulators, splitters, scanners, etc.) were proposed,
      but due to high fabrication cost and/or high operation voltages they were
      considered impractical. For the first time to our knowledge we propose to use
      electro-optic (EO) polymers for the fabrication of FIG devices. This alleviates
      these limitations and makes this powerful device fabrication paradigm applicable
      in practice. We theoretically predict and experimentally demonstrate FIG in EO
      polymers. We also propose the idea of new class of devices--multifunctional
      optical devices that can completely change their functionality on the fly.

PMID- 20154759
TI  - Real-time slope mapping and defect detection in bent plates using Talbot
      interferometry.
AB  - We demonstrate a simple method for obtaining slope contours of bent plates using
      Talbot interferometry. The technique has been used to map slope contours of
      polymethyl methacrylate specimens of different shapes. The Talbot image of a
      coarse grating is projected onto a specimen such that the self-image is
      backreflected onto the same grating again. As a Talbot interferometer is
      basically a grating shearing interferometer, it results in the generation of
      characteristic slope maps of the specimen under test. Results of the
      investigation match well with other slope-mapping techniques. Validation of
      experimental results with theoretical predictions in the case of a cantilever
      beam specimen has been undertaken. Accuracy of about 4.7% with respect to
      theoretical predictions is obtained.

PMID- 20154760
TI  - Maclaurin-series method for calculating dispersion in arrayed-waveguide grating
      multiplexers.
AB  - We present a Maclaurin-series method for calculating the dispersion from phase
      error and amplitude distributions in arrayed waveguide grating (AWG)
      multiplexers. By using this method, we can easily derive the intercept, the
      gradient, and the curvature of the dispersion in the center frequency region of a
      passband. A third-order Maclaurin series was calculated by using the measured
      phase error and amplitude distributions of AWGs having a channel frequency
      spacing of 12.5 GHz. The calculated results are in good agreement with the
      dispersions measured with an optical network analyzer. We also discuss the
      physical effect of the phase error on dispersion by assuming certain limited
      cases.

PMID- 20154761
TI  - Absolute refractive index measurement method over a broad wavelength region based
      on white-light interferometry.
AB  - We report a simple method of measuring the absolute values of the phase
      refractive index of an optical material of a flat plate shape over a wide
      spectral range at a single measurement run. A white-light interferometric
      technique with angle rotation of the optical plate sample located in one of the
      interferometer arms was used in this method. The validity of this method was
      proved by measuring the absolute phase refractive indices of flat plate samples
      of fused silica and BK7, and by comparing them with calculated values from their
      well-known Sellmeier dispersion formulas. The accuracy of this refractive index
      measurement method was within 0.002, which can be further improved by enhancing
      the angle measurement accuracy of the angle rotating stage used in this method.

PMID- 20154762
TI  - Optimal transmitter power of an intersatellite optical communication system with
      reciprocal Pareto fading.
AB  - This paper shows that optical signal transmission over intersatellite links with
      swaying transmitters can be described as an equivalent fading model. In this
      model, the instantaneous signal-to-noise ratio is stochastic and follows the
      reciprocal Pareto distribution. With this model, we show that the transmitter
      power can be minimized, subject to a specified outage probability, by
      appropriately adjusting some system parameters, such as the transmitter gain.

PMID- 20154763
TI  - Surface plasmon resonance in a hexagonal nanostructure formed by seven core shell
      nanocylinders.
AB  - A hexagonal nanostructure formed by seven core shell nanocylinders filled with
      different dielectric cores is investigated. The surface plasmon resonance in such
      a hexagonal nanostructure under conditions of different illumination wavelengths,
      dielectric cores, angles of incidence, and thicknesses of silver shells is
      studied by use of the finite element method. Simulation results show that the
      resonant wavelength is redshifted as the dielectric constant and the size of the
      core increase. The peak resonant wavelength and the local field enhancement are
      approximately proportional to the radius of the dielectric core. Additionally,
      the surface plasmon field excited by TM-polarized light at the incident angle of
      theta=15 degrees is exactly a linear combination of those excited at incident
      angles of theta=0 degrees and 30 degrees, confirming the linear nature of the
      surface plasmon resonance in a nanostructure formed by linear media.

PMID- 20154764
TI  - Atmospheric degradation correction of terahertz beams using multiscale signal
      restoration.
AB  - We present atmospheric degradation correction of terahertz (THz) beams based on
      multiscale signal decomposition and a combination of a Wiener deconvolution
      filter and artificial neural networks. THz beams suffer from strong attenuation
      by water molecules in the air. The proposed signal restoration approach finds the
      filter coefficients from a pair of reference signals previously measured from low
      humidity conditions and current background air signals. Experimental results with
      two material samples of different chemical compositions demonstrate that the
      multiscale signal restoration technique is effective in correcting atmospheric
      degradation compared to individual and non-multiscale approaches.

PMID- 20154765
TI  - Applied optics of optics and opticists.

PMID- 20154766
TI  - Optical activities in industry.

PMID- 20154767
TI  - Plexiglas: a Convenient Transmission Filter for the FIR Spectral Region.

PMID- 20154768
TI  - Fresnel zone plate: a second-order approximation.

PMID- 20154769
TI  - Simple laser interferometer with variable shear and tilt.

PMID- 20154770
TI  - Rotating diffraction grating laser beam scanner.

PMID- 20154771
TI  - Restored impulse response of finite-range image deblurring filter.

PMID- 20154772
TI  - Laser Writing-Reading with SmS Thin Films.

PMID- 20154773
TI  - Pulse modulation effect on velocity fringes.

PMID- 20154774
TI  - Bibliography of various optical testing methods.
AB  - A bibliography of various methods of optical testing has been compiled, with the
      papers grouped by subject, e.g., Fizeau interferometer. Only interferometer
      papers-or those on similar devices-that have direct relevance to shop testing are
      included. This reasonably complete compendium should be of use to workers in
      optical fabrication and testing.

PMID- 20154775
TI  - Packing density in holographic systems.
AB  - The holographic packing density is derived for any plane in a coherently
      illuminated optical system. The gain in packing density relative to the object
      plane is given. A two-lens optical system in which a condenser lens provides high
      packing densities and an imaging lens provides sufficient resolution is superior
      to a system in which a single lens performs both functions.

PMID- 20154776
TI  - Holographic associative memory and processor.
AB  - Several concepts for associative holographic memories have been previously
      described that rely upon Braggangle selection in. the recording medium during
      parallel search readout of the memory. A new format of page-oriented associative
      holographic memory is proposed in this paper that relies upon constructive and
      destructive interference to provide a null signal output for the perfect match
      during associative search readout. The readout signal in this new format is not
      affected by page size, and the memory format also allows for limited parallel
      digital processing, making the holographic approach more compatible with present
      electronic associative memory processors.

PMID- 20154777
TI  - Speckle reduction in holography with a spatially incoherent source.
AB  - High quality holograms of flat objects are produced by developing an achromatic
      fringe system that consists of a monochromatic but spatially incoherent source, a
      holographic beam splitting device, and a pair of Fourier transform lenses. The
      effects of using an incoherent extended source and the transfer characteristics
      of the holograms are discussed. Emphasis is also placed on the advantages of
      developing lens Fourier transform holography along with the practical lens
      systems. A further possible extension of the system to attain high storage
      density as well as high quality holograms is proposed by making use of a new type
      of pseudorandom phase sequence.

PMID- 20154778
TI  - Technique for measuring refractive index changes in photochromic materials.
AB  - We describe a new technique for measuring the refractive index change associated
      with the photoinduced absorption change in photochromic materials. The technique
      involves writing a thick holographic grating in a sample of the material and
      observing the interaction of the grating with the beams used to write it. Only
      three relative intensity measurements are required, and many of the difficulties
      of previous techniques are avoided. We have demonstrated the technique in
      experiments on a photodimer material. These experiments also provide an example
      of a modulated transmission effect related to the Borrmann effect.

PMID- 20154779
TI  - Refractive Index Measurements in Fused NaNO(3) and KNO(3) by a Modified
      Thermooptic Technique.
AB  - A thermooptic technique for studying the temperature dependence of refractive
      index of liquids at room temperature has been modified and applied to the study
      of molten NaNO(3) and KNO(3) within a temperature range of some 80 K above the
      melting point for five different wavelengths within the visible spectral range.
      The experiments show a temperature dependence of the polarizability for the two
      salts as calculated from the Lorentz-Lorenz formula, which cannot be explained by
      experimental inaccuracy.

PMID- 20154780
TI  - Refractive index measurement of high refractive index glass beads.
AB  - The refractive index of a small sphere and rod was measured by a method using the
      theory of rainbow that the minimum deviation angle of a single internally
      reflected ray from a sphere depends solely on the relative refractive index of
      the sample to the medium. Experimental results confirmed an accuracy of about 1%.
      This method is particularly suited to materials of high refractive index, because
      the conventional immersion method needs liquid of higher refractive index, which
      inevitably contains such poisonous elements as As.

PMID- 20154781
TI  - Cryogenic infrared grating spectrometer.
AB  - A liquid-helium-cooled Ebert-Fastie grating spectrometer for use in a sounding
      rocket is described. Twelve detectors and associated filters separate the 5-70
      microm spectral range into twelve intervals, each of which is scanned as the
      grating is rotated. The instrument was launched into an aurora from Fort
      Churchill, Canada, but a cryogenic failure occurred early in the flight, and only
      a small amount of data was obtained.

PMID- 20154782
TI  - Tunable Diode Laser High Resolution Spectroscopic Measurements of the nu(2)
      Vibration of Carbon Dioxide.
AB  - A tunable diode laser spectrometer was used for high resolution measurements on
      the Q-branch of the nu(2) vibration of carbon dioxide. The infrared source was a
      current tuned Pb(0.936)Sn(0.064)Se diode laser. A 1-m gas cell was designed to
      allow variation of temperature (200-300 K) at 1-50 torr of 320 ppm mixtures in
      nitrogen. Owing to the narrow linewidth of the diode laser, true line shapes may
      now be measured well into the Doppler region. Line shapes and intensities of
      several rotational lines (J </= 34) have been measured as a function of pressure
      and temperature. Initial measurements tend to confirm the theoretical predictions
      of Drayson as to relative line positions, but show linewidths higher than
      predicted by Yamamoto et al. The line strengths, at low temperatures, appear to
      be about 12% greater than those predicted by Drayson.

PMID- 20154783
TI  - Measurement of very low absorption coefficients by laser calorimetry.
AB  - Laser calorimetric or thermal rise techniques are useful for the determination of
      very low absorption coefficients in solids. A number of improvements in this
      technique are described of which the most important is a means of separating
      surface and bulk absorption. These techniques have been applied to study alkali
      halides in the ir but are applicable where laser sources of sufficient power are
      available.

PMID- 20154784
TI  - Precision bounds to ellipsometer systems.
AB  - The theoretical precision attainable from a number of types of ideal null and
      photometric ellipsometers is investigated quantitatively. Photometric and
      modulated null ellipsometer systems are shown to be approximately comparable with
      respect to precision when operating under shot-noise limited conditions.
      Differences are due principally to intrinsic detector noise levels, which are
      more significant in null designs. The equations derive can be used to estimate
      practical measurement limits or to choose components to achieve a specific
      objective.

PMID- 20154785
TI  - Integrating Spheres for Measurements Between 0.185 microm and 12 microm.
AB  - A new system for absolute total diffuse transmission and reflection measurements
      using two integrating spheres is described; it extends the normal spectral range
      into the uv and ir. Furthermore, as part of the system, a unique self-calibrating
      technique has been incorporated. One sphere is coated with BaSO(4) for use
      between wavelengths of 0.185 microm and 2.0 microm, and the other is coated with
      sulfur flowers for use between 1.5 microm and 12 microm. The BaSO(4) and sulfur
      fulfill the diffuseness and high reflectance characteristics necessary for an
      integrating sphere. The feature of the system for calibration of the spheres uses
      goniophotometric measurements of diffuse transmission and reflection. These
      reflection intercalibrations are better in the visual range than a fraction of a
      percent (absolutely); however, transmission intercalibrations on quasi-specular
      samples may have absolute differences of several percent, thus requiring a
      goniophotometric transmission measurement as the valid determination.

PMID- 20154786
TI  - Integrating-sphere fluorescence cells: instrumental errors in fluorescence
      lifetimes and intensities.
AB  - An integrating-sphere fluorescence cell is described for measurement of
      intensities, yields, and lifetimes of long-lived gas phase molecules under
      collision-free conditions. The cell has high light-gathering efficiency and
      provides uniform sampling and a well-defined source for imaging onto the
      detection system. The signal gain compared to a conventional fluorescence cell of
      similar dimensions may be as great as 100-fold. Expressions are developed for
      measurement errors as a function of cell radius. For equal errors the integrating
      sphere radius must be 2-3 times that of a conventional cell.

PMID- 20154787
TI  - Measurements on Lambertian objects: some novel approaches.
AB  - The problem of measuring Lambertian objects at close distances is examined for
      both a sphere and a cone irradiated by a plane wave. The equations describing the
      scattered power collected by a receiver are derived using the principles of
      radiometry, and some experimental results are provided.

PMID- 20154788
TI  - Edge-On Diffraction of a Gaussian Laser Beam by a Semi-infinite Plane.
AB  - A He-Ne laser beam is used here to illuminate a razor blade at edge-on incidence.
      The incident light is found to be scattered into a single straight cone of
      circular cross section. The tip of this cone of diffracted light lies at the
      point of incidence, its axis coincides with the prolongation of the razor edge,
      and its halfangle is equal to the angle of incidence. Such cones formed by a
      family of diffracted rays are basic to the so-called geometrical theory of
      diffraction. However, the properties and geometrical laws associated with the
      diffracted rays are derived analytically here by application of the boundary
      diffraction wave theory. The experimental results are in agreement with
      theoretical predictions.

PMID- 20154789
TI  - Temporal-Frequency Spectra for Waves Propagating over Straight and Folded Paths:
      a Comparison.
AB  - Expressions are determined for the relationship between the crosswind speed and
      the temporal-frequency spectra of the log-amplitude fluctuations of plane and
      spherical waves propagating over folded paths in a turbulent atmosphere. The
      results of the spherical wave indicate that in addition to information about
      turbulent motion, the spectral content contains a path position modulation that
      depends on the detector displacement from the center of the wave. This
      displacement may lead to errors in the determination of turbulent motion from
      optical measurements.

PMID- 20154790
TI  - Iterative image restoration.
AB  - The projection method of solving a set of linear equations was used to restore
      linearly degraded images. The advantages of this method are that it always
      converges, it can readily make use of a priori information about the image, and
      it does not need excessive computation time. Experimental results indicate that
      this method could potentially achieve superresolution.

PMID- 20154791
TI  - Modulation contrast microscope.
AB  - A new microscope imaging system, modulation contrast, has been devised that
      reveals phase gradients; the image intensity is proportional to the first
      derivative of the optical density in the object. The modulator, a special filter,
      is placed in the Fourier plane, a plane conjugate with a slit aperture. The image
      of the slit aperture is registered within a gray region of the modulator; on one
      side of the gray region is a region of low transmittance and on the other side, a
      region of maximum transmittance. The modulator processes opposite gradients to
      produce opposite intensities, creating an optical shadowing effect. The dark
      region may be outside the optical system when the gray region is offset to the
      edge of the Fourier plane, to achieve maximum resolution. Modulation contrast is
      directional and capable of optical sectioning, revealing details without
      obscuring effects of structures above and below the plane of focus. The imaging
      theory of microscope optics has been extended to include effects of phase
      gradients. Phase gradients distribute the zero order across the Fourier plane.
      Intensity of the gradient's image is controlled by the zero order of the gradient
      diffraction pattern.

PMID- 20154792
TI  - Dynamics of thin-film thermal detectors in infrared imaging systems. 2: imaging
      of fixed and moving objects.
AB  - In a previous paper we derived the basic equations and the spatial and temporal
      modulation transfer functions (MTF) for a three-dimensional model of thin-film
      thermal imaging systems. Here we discuss the imaging of fixed and moving objects.

PMID- 20154793
TI  - Self-scanned digicon: a digital image tube for astronomical spectroscopy.
AB  - We have successfully fabricated, tested, and operated a digital image tube
      consisting of a magnetically focused image intensifier tube in which a self
      scanned linear array of 1024 silicon photodiodes operating in the EBS mode serves
      as the photoelectron image detector, amplifier, and intermediate image storage
      device. Integral on-chip MOS shift registers driven by an external clock
      sequentially interrogate the photodiodes through MOS FET multiplex switch arrays.
      Each output frame is a sequence of 256 analog pulses on each of four video lines.
      Laboratory and observing tests show that the output signal is photoelectron shot
      noise limited over at least a range of 1-10(5) detected photoelectrons per
      picture element, indicating that single photon detection is achieved. High
      resolution astronomical spectroscopy has been carried out in the coude
      spectrograph of the 2.7-m telescope at McDonald Observatory. Examples are shown.

PMID- 20154794
TI  - Optical pump system for mode-controlled laser operation.
AB  - Generation of efficient mode-controlled emission with optically pumped laser
      systems requires a special resonator configuration in combination with an
      efficient pump system that homogeneously pumps the active medium. Several pump
      systems were investigated for their qualification. As a result an improved
      version of an elliptical cylinder system turned out to be favorable. Highly
      reproducible fundamental mode emission with a pulsed YAG laser system could be
      achieved.

PMID- 20154795
TI  - Gaussian modes in high loss laser resonators.
AB  - Matrix techniques are applied to the mode analysis of laser resonators having
      spherical mirrors and Gaussian profiles of the mirror reflectivity. These same
      analytical methods provide a useful approximation to the mode and loss
      characteristics of conventional resonators having an abrupt discontinuity of the
      reflectivity. Mode selection in apertured waveguides and resonators is also
      discussed.

PMID- 20154796
TI  - Optical waveguides fabricated by preferential etching.
AB  - We introduced a new technique of fabricating optical waveguides by first
      preferentially etching the waveguide grooves, which can be either cusp-shaped or
      cup-shaped in cross section, and then filling the grooves with organic films by
      solution-deposition technique. With the chemical etching technique, perfectly
      smooth reflecting waveguide walls and well-defined waveguide profiles can be
      easily produced and reproduced with an accuracy that no other existing
      fabrication techniques can achieve. In our experiments, silicon was chosen as the
      base material for possible future integration of optical and electronic
      components.

PMID- 20154797
TI  - Tapered velocity couplers for integrated optics: design.
AB  - The operation of tapered velocity couplers is analyzed from the point of view of
      mode conversion between local-normal modes. An approximate coupled mode
      representation of the local-normal modes is used with a step transition model to
      estimate analytically power transfer. This yields an upper limit for the maximum
      permissible variation in mode synchronism across the coupler to achieve
      satisfactory coupler operation. The analysis has also been used to demonstrate
      the importance of obtaining a large total change in mode synchronism to minimize
      coupler length.

PMID- 20154798
TI  - Beam coupling to linear waveguides using lenslike waveguides.
AB  - Theoretical coupling of a guided Gaussian beam in a planar dielectric waveguide
      to a rectangular waveguide using a lenslike coupling region is investigated. The
      coupling region is formed by varying the thickness of the planar waveguide. When
      the center height of a sample structure is of the order of 1.58 wavelengths, a
      100-lambda wide beam can be coupled to a linear waveguide 5 lambda wide in a
      distance of 957.35 lambda. The theoretical coupling efficiency approaches 100%.

PMID- 20154799
TI  - Current-controlled phase retardation plate.
AB  - A plate of fused quartz mounted in the jaws of a magnetic clamp serves as a
      current-controlled phase retardation plate. The current to the clamp controls the
      stress on the quartz plate, and hence the amount of stress-induced birefringence.
      The device described here can be used in a dc mode as a fixed phase retardation
      plate or in an ac mode as a polarization modulator at frequencies up to several
      hundred hertz. This device offers several advantages over other polarization
      modulators available.

PMID- 20154800
TI  - Index matching reduces peak electric fields in thin-film polarizers.
AB  - Multilayer thin-film polarizers with. and without antireflection layers between
      the repeating groups of layers and the mediums at both ends of the multilayer are
      compared for optical electric field levels. It is shown that standing waves can
      build up the electric fields to higher levels without antireflection layers than
      with them. Relations are derived between optical throughput and electric field
      levels for oblique propagation. Numerical values are given for a particular
      example. A 70% gain in throughput is possible before a given electric field level
      is reached if antireflection layers are used compared to not using them. Electric
      fields in the polarizer are compared to those in a V coat. The V coat may handle
      twice the throughput of the polarizer if the high index material limits allowable
      levels.

PMID- 20154801
TI  - Optical fiber-stripline-coupler.
AB  - A device for coupling a glass fiber to a stripline of an integrated optical
      device is described. The adjustment is sufficiently precise to connect single
      mode waveguides. In the case of single-mode fiber-fiber-connections, coupling
      efficiencies between 85%h and 95% were measured.

PMID- 20154802
TI  - Robust fiber-optic interconnecting wires using redundancy.
AB  - Situations can occur, in fiber-optic information transmission systems, where
      armor sheathing of the fibers is not sufficient physical protection. In this
      paper we study the use of redundancy to provide the required additional
      protection against loss of signal. Two methods are examined: one where each
      redundant path is uncoupled to all others and another where paths are
      longitudinally coupled, allowing energy to pass freely between fibers. It is
      shown that coupling always has a statistical advantage, although this advantage
      may be small in some cases. The parameters needed to produce effective interfiber
      coupling are then investigated, and a configuration is proposed for such a
      coupled wire system.

PMID- 20154803
TI  - Patents.
AB  - 3,712,198; 3,718,397; 3,714,879; 3,719,416; 3,720,457; 3,721,170; 3,805,051;
      3,805,052; 3,820,870; 3,837,727; 3,837,732; 3,838,910; 3,838,911; 3,840,290;
      3,840,701; 3,840,741; 3,841,734; 3,841,736; 3,843,235; 3,844,640.

PMID- 20154804
TI  - Applied optics of optics and opticist.

PMID- 20154805
TI  - Infrared reflectance of silicon oxide and magnesium fluoride protected aluminum
      mirrors at various angles of incidence from 8 microm to 12 microm.

PMID- 20154806
TI  - Optical activies in Ind ustry.

PMID- 20154808
TI  - Film-fiber coupling in integrated optics.

PMID- 20154807
TI  - Measuring total film thickness: an experimental procedure.

PMID- 20154809
TI  - Prevention of fire damage due to exploding dye laser flashlamps.

PMID- 20154810
TI  - Measurements of the absorption coefficient in fiber optical waveguides using a
      calorimetric technique.

PMID- 20154811
TI  - Novel hybrid optical correlator: erratum.

PMID- 20154812
TI  - Moire contouring: mathematical analysis.

PMID- 20154813
TI  - Stratospheric aerosol parameters for the Fuego volcanic incursion.

PMID- 20154814
TI  - Isoline method of portraying atmospheric attenuation of laser radiation.

PMID- 20154815
TI  - Laser fusion target illumination system.
AB  - Laser fusion experiments require the focusing of very intense pulsed laser beams
      onto very small fuel pellets. All reported experiments to date have used lenses
      to focus one or more laser beams onto the target. This paper describes a combined
      refractive/reflective illumination system that provides nearly uniform irradiance
      with nearly orthogonal incidence over the complete spherical target, with only
      two laser beams. This illumination system was used in the experiments that
      produced the first known symmetric target implosions. Furthermore, these
      experiments produced what we believe were the first thermonuclear neutrons
      generated by a laser-driven implosion.

PMID- 20154816
TI  - Ellipsoidal illumination system optimization for laser fusion experiments.
AB  - It is shown that nearly uniform and orthogonal illumination of a spherical target
      may be realized by defocusing the ellipsoidal mirror system devised by C. E.
      Thomas.

PMID- 20154817
TI  - Specular aspheric surface to obtain a specified irradiance from discrete or
      continuous line source radiation: design.
AB  - A differential equation is obtained for reflecting surface that will distribute
      radiation originating from a linear array of discrete sources or a continuous
      line source into a specified illuminance over an arbitrary receiver surface that
      is symmetric about the line. The equation is solved numerically for the special
      case of two discrete emitting elements and also for a continuous Lambertian
      source.

PMID- 20154818
TI  - Three-mirror stable resonator for high power and single-mode lasers.
AB  - A stable, high Q, three-mirror resonator is proposed for the optimum output
      coupling and mode control of high power moderate-gain lasers. Theoretical
      calculations on the beam intensity distributions, spot sizes, and stability
      conditions are given. Alignment tolerance for a limiting case is discussed.
      Experimental results with a high power argon-ion plasma tube and a three-mirror
      stable resonator agree with the theory.

PMID- 20154819
TI  - Acoustical wave effects on the beam quality of a high energy CO electric
      discharge laser.
AB  - A high efficiency CO, e(-)-beam sustained electric discharge laser has been
      operated at 500 J/pulse with near diffraction limited beam quality. The high
      Fresnel number cavity configuration employs a confocal unstable resonator with a
      geometric magnification of approximately 2.5. In spite of the high quantum
      efficiency of the CO laser, significant fractions of the pumping energy are
      absorbed in the gas as bulk heating giving rise to acoustic waves that refract
      portions of the light from the beam axis. The strength of the density waves have
      been measured using interferometric techniques and correlate well with the
      observed refraction of the laser light.

PMID- 20154820
TI  - Laser tuners using circular piezoelectric benders.
AB  - This paper presents the results of an experimental evaluation of a new type of
      piezoelectric ceramic device designed for use as a laser mirror tuner. Thin
      plates made from various materials were assembled into a circular bimorph
      configuration and tested for linearity of movement, maximum travel, and resonant
      frequency for varying conditions of clamping torque and mirror loading values.
      Most of the devices tested could accept mirror diameters up to approximately 1.3
      cm and maintain a resonant frequency above 2 KHz. Typical mirror translation
      without measurable tilt was +/-20 microm or greater for applied voltages of less
      than +/-300 V.

PMID- 20154821
TI  - Iodine stabilized laser with three internal mirrors.
AB  - The construction and operation of an He-(20)Ne laser stabilized by saturated
      absorption in (129)I(2) vapor are described. The laser is of fused silica
      construction with internal mirrors. The interaction of the iodine absorber with
      the oscillating mode is modified by the use of a three-mirror cavity with a
      control system employing simultaneously first- and third-harmonic error sensing.
      Measurements are presented of the frequency stability of the laser and its
      wavelength against the (86)Kr standard. If the Rowley-Hamon model of the krypton
      line profile is assumed and the defined wavenumber is assigned to the mean of the
      peak and the centroid, the measured wavelength of the m hyperfine component is
      632991 327 +/- 0.7 fm.

PMID- 20154822
TI  - Graded-gain dye laser amplifiers: an experimental investigation.
AB  - The influence of inhomogeneous distributions of gain and refractive index
      produced by the pumping radiationon the performance of dye laser amplifiers is
      discussed. Experimental measurements in capillary cylindrical cells and planar
      cells are reported for single-pass, double-pass, and ring configurations. Gain
      factors up to 8.5 x 10(4) have been obtained at low signal input with rhodamine
      6G in ethanol. A saturated gain of 5 x 10(3) at 100-mJ output with an over-all
      efficiency of 0.1% has been achieved without full optimizationof the amplifier
      parameters. The reported results indicate that a two-stage double-pass amplifier
      driven by a dye laser oscillator in the milliwatt region can be used as an
      efficient high energy light source.

PMID- 20154823
TI  - Ellipsometric investigation of quadratic electrooptic and electrostrictive
      effects with anodic niobium pentoxide films.
AB  - Anodic oxide films on niobium were studied in situ during formation using a
      computer-controlled ellipsometer at a wavelength of 6328 A. They were found to be
      optically homogeneous, isotropic, and nonabsorbing with no field applied but to
      become anisotropic (optically uniaxial with optic axis normal to the film
      surface) with field applied. The ordinary and extraordinary indices decreased,
      and the thickness increased quadratically with applied field. Values are reported
      for the refractive index of niobium and of the oxide, and these are compared with
      previous reports. The quadratic electrooptic coefficients for the oxide are
      reported and are of the same order of magnitude as those for oxygen-octahedra
      ferroelectrics and somewhat greater than the values for tantalum pentoxide films.

PMID- 20154824
TI  - Two-dimensional optics with surface electromagnetic waves.
AB  - Two-dimensional optical effects were observed for surface electromagnetic waves
      (SEW) on metals at lambda = 3.55 cm. Refractive processes with prisms and lenses
      established Snell's law experimentally. Reflection with prisms and metal sheets
      established the law of reflection and indicated that radiative losses were small
      and that Fresnel's equations hold to a good approximation for the reflectivities
      of SEW. A two-dimensional SEW grating was made and first-order diffraction
      observed. Although the experiments were performed at microwave frequencies, the
      principles are usable for two-dimensional SEW optics at least as far as the near
      ir. It was shown that the propagation constant of the SEW with an overlayer
      material is as though the SEW propagates entirely in the overlayer material. That
      is, losses in the metal substrate were negligible.

PMID- 20154825
TI  - Multilayer antireflection coatings: theoretical model and design parameters.
AB  - A theoretical model for multilayer antireflection coatings is presented on the
      basis of the theory of all-dielectric Fabry-Perot interference filters. Effective
      interfaces are employed, and a new concept of a replacement pair consisting of
      two layers is introduced. It is shown that incorporation of this pair in a
      multilayer yields low reflectance values over a wide spectral range. This
      theoretical model is then used to design various coatings, and three typical
      examples are given and discussed. The various parameters that control the
      reflectance behavior in the region of low reflection are also discussed.

PMID- 20154826
TI  - Optical constants of far infrared materials. 3: plastics.
AB  - Room temperature optical constants of plastic materials have been measured over
      the 50-350-cm(-1) spectral range. The materials reported include high density
      polyethylene, TPX, Aclar, Kapton, Surlyn, and Mylar. All except TPX are available
      in sheet form and exhibit birefringence as a consequence of stretching during the
      manufacturing process. Only the average of the two sets of optical constants is
      reported for each material. The refractive index was calculated from the
      channeled spectrum as observed in reflection from the sample, while the
      absorption coefficient was determined, in all cases but polyethylene, from a
      transmission measurement.

PMID- 20154827
TI  - Glass fiber hermetic seals using a CO(2) laser.
AB  - Glass fibers of approximately 0.13-mm diam have been hermetically sealed through
      windows of Corning Code 7740 glass and Code 7052 glass, and into B(2)O(3)-3SiO(2)
      glass as well. The seals were made with a 50-W CO(2) laser at a power level of
      about 5 W. Transmission loss tests show a transit loss of <0.2 dB for a B(2)O(3)
      3SiO(2) clad fused silica fiber through a Corning Code 7740 glass window.

PMID- 20154828
TI  - Skew rays in optical fibers.
AB  - In order to justify the use of meridional analysis, the authors solve the Eikonal
      equation without approximationin two cases of index profile. Limit conditions are
      studied and attention is given to skew rays with inclination over the fiber axis
      greater than the critical angle of the meridional case. It is shown that skew
      rays introduce a queue in the impulse response of a fiber. In the case of solid
      state laser sources, they do not carry significant energy, and then can be
      neglected.

PMID- 20154829
TI  - Shuttle pulse measurements of pulse spreading in an optical fiber.
AB  - Partially transparent mirrors were pressed against fiber ends so that the length
      dependence of pulse spreading could be determined without cutting the fiber into
      pieces. Measurements were made by comparing the widths of laser pulses (lambda =
      0.9 microm) through the output end mirror, which returned from 9(1/2) successive
      round trips (2014-m extrapolated length) along a 106-m multimode fiber. Mode
      mixing was significant in this fiber (fabricated by Corning Glass Works), and a
      square root of length pulse width dependence was observed. However, some of the
      mode-mixing effects on pulse width were caused by the way in which the fiber was
      wound on a drum.

PMID- 20154830
TI  - Length dependence of pulse dispersion in a long multimode optical fiber.
AB  - Shuttle pulse measurements performed on a 1280-m long multimode optical fiber
      were used to determine pulse dispersion along a 6400-m extrapolated length. The
      fiber's steady-state mode coupling length was determined without breaking the
      fiber. The impulse responses for one, three, and five trips through the fiber
      were recorded and Fourier transformed to yield the corresponding baseband
      frequency responses. It was concluded that the coupling length was approximately
      840 m, and that the impulse response became increasingly more symmetrical for
      fiber lengths beyond this coupling length. This agrees with theory.

PMID- 20154831
TI  - Shuttle pulse measurements of pulse spreading in a low loss graded-index fiber.
AB  - Shuttle pulse measurements in a multimode optical fiber were used to determine
      pulse dispersion, at lambda = 0.9-microm wavelength, in eight increments from 148
      m to a 2516-m extrapolated length. There was relatively little mode mixing in
      this low loss fiber (minimum loss = 1.7 dB/km at lambda = 1.04 microm), and the
      observed pulse width was primarily due to the grading of the refractive-index
      profile.

PMID- 20154832
TI  - Optical processing of pulsed Doppler and FM stepped radar signals.
AB  - A real-time radar processor with an electron beam addressed KD(2)PO(4) light
      valve as the input electrical-to-optical transducer is described. The input
      format, output plane pattern, and the required optical processing of pulsed
      Doppler and FM stepped radar data on this system are discussed. Experimental
      output plane patterns with actual radar data are presented. Although these data
      are processed off-line, the processing is performed at real-time data rates.

PMID- 20154833
TI  - On-line data reduction with a prism spectrometer.
AB  - We describe the hardware and software aspects of an automatic spectroscopy system
      based upon a programmable calculator and a prism monochromator. Linear spectral
      presentation is obtained by a fourpoint Aitken-Lagrange interpolation performed
      at each data point. The interpolation subroutine, which is also useful for data
      logging with thermocouples, is described in detail. Both open- and closed-loop
      applications of the system to reflectance and modulation spectroscopies are
      discussed, and additional uses are suggested.

PMID- 20154834
TI  - Diffuse reflectance spectroscopy: a comparison of the theories.
AB  - The various theories of diffuse reflectance spectroscopy are compared
      mathematically, and it is concluded that the modified particle model theory is
      probably the most nearly correct. If so, the comparison shows that the simple,
      easily applied simplified particle model theory is approximately valid for
      relative index of refraction values of 1.5-2.5 and that the Kubelka-Munk
      remission function is approximately applicable in the traditional sense.
      Expressions were obtained for the Kubelka-Munk constants in terms of the
      fundamental optical parameters, and the depth of penetration of radiation into a
      powdered sample was investigated.

PMID- 20154835
TI  - Phase correction for a Michelson interferometer with misaligned mirrors.
AB  - The phase correction for a Michelson interferometer with misaligned mirrors in
      converging light is shown to give rise to a quadratic phase shift. In general,
      the calculation of a spectrum from the measured interferogram needs phase
      correction. Phase corrections have been well worked out for the cases of a linear
      phase shift and a phase that is slowly varying. The standard procedures for
      correcting calculated spectra need to be modified, however, to remove any phase
      errors resulting from misaligned mirrors.

PMID- 20154836
TI  - Unfolding first and second order diffracted radiation when using synchrotron
      radiation sources: a technique.
AB  - A technique is presented of using a single calibrated XUV detector for
      radiometric measurements of synchrotron radiation after the radiation passes
      through a monochromator that produces a mixture of first and second order
      diffracted radiation. Irradiance measurements are made with the synchrotron
      source operating at two different energies for the orbiting electrons. The known
      change in the spectral distribution produced by the electron energy change is
      used to calculate the flux in both first and second order. The dependence of the
      precision of these determinations on the two detected currents and on the
      detector calibration at both first and second order wavelengths is calculated.
      Experimental results using the National Bureau of Standards synchrotron (SURF-I)
      are presented, and anticipated results for the new NBS electron storage ring
      (SURF-II) are calculated.

PMID- 20154837
TI  - Polarization of light reflected from rough planetary surface.
AB  - A calculation is made of the luminance and polarization of light due to single
      and double reflections from the faces of particles in a surface composed of
      random, irregular particles using equations of electromagnetic waves and
      materials with a complex index of refraction. Some geometric properties of
      shadows are derived and used. Good agreement is obtained between these results
      and measurements of polarized light from Mars, Mercury, and the moon, including
      the phenomenon of negative polarization at small phase angles. Negative
      polarization is found to be caused by shade and shadows affecting the double
      reflected rays. Graphical results are provided for materials of varied real and
      complex indices of refraction. The model can be used to calculate polarization
      and luminance of rough astronomical bodies and surfaces as a function of the
      viewing angle. Calculated ratios of single-reflected, double-reflected, and
      randomly diffused light can be related to the surface structure and optical
      properties of the material.

PMID- 20154838
TI  - Matrix transform optical calculus for generalized linear dielectric media.
AB  - Described here is an optical calculus developed to meet the practical need for
      ray tracing in new classes of imaging devices such as liquid crystals. The
      calculus is intended for computer programming and uses a method of matrix
      transform to eliminate redundancy, thereby reducing computer programming and
      execution time. The calculus, a coherent calculus of the Jones type, is also
      useful in interpreting the interaction between the components of a light wave
      when retardation, optical activity, and isotropic nonisotropic linear and
      circular dichroism are all present simultaneously.

PMID- 20154839
TI  - Threshold detection in an on-off binary communications channel with atmospheric
      scintillation.
AB  - The optimum detection threshold in an on-off binary optical communications system
      operating in the presence of atmospheric turbulence has been investigated
      assuming a Poisson detection process and log normal scintillation. The dependence
      of the probability of bit error on log amplitude variance and received signal
      strength has been analyzed, and semi-emperical relationships to predict the
      optimum detection threshold have been derived. On the basis of this analysis, a
      piecewise linear model for an adaptive threshold detection system is presented.
      The bit error probabilities for nonoptimum threshold detection systems have also
      been investigated.

PMID- 20154840
TI  - Atmospheric NO(2) determination by 442-nm laser induced fluorescence.
AB  - An atmospheric monitor with a detectability of 0.6 ppbv, utilizing a compact He
      Cd laser at 442 nm for excitation of the NO(2) molecules is described. Photon
      counting techniques were employed to detect the NO(2) fluorescence transmitted
      through a bandpass liquid solution filter that did not fluoresce upon absorption
      of scattered laser light. Operational characteristics of the instrument are
      described. Results obtained in ambient air monitoring are presented.

PMID- 20154842
TI  - SIT vidicon with magnetic intensifier for astronomical use.
AB  - We have coupled a magnetic intensifier to an intensified silicon target vidicon.
      The output and controls are digital and designed to optimize the computer
      analysis of the astronomical data. A coarse sweep 128 x 128 lines gives a large (
      approximately 10:1) pixel to pixel modulation. Photoelectron noise is comparable
      to readout noise. Tube preparation is by a single light flash, ten beam erases,
      and a shift in cathode potential before integrate. The real time numerical
      picture analysis programs find stars, integrate their intensity, determine
      background, calculate variations, etc. and, in general, are far more useful than
      visual displays. Star intensities are linear with integrate time and reproducible
      to 3%

PMID- 20154841
TI  - Detection of atmospheric pollutants: a correlation technique.
AB  - The objective of this effort was to derive suitable correlation functions for
      monitoring the atmosphere for specified pollutants by remote ir sensing
      techniques. The correlation function for a particular target pollutant is
      calculated by the simplex optimization method. This technique constrains the
      response of the gas detection system to less than some arbitrary constraint limit
      for background changes while optimizing system response to the target pollutant.
      The response to a target pollutant was 2 to 3 times greater than any background
      induced change over a period of 2 weeks. The technique is applicable to a wide
      range of spectral analytical problems and may apply to process control as well as
      remote sensing techniques, particularly in pollution monitoring applications.

PMID- 20154843
TI  - Silicon diode array vidicons at the telescope: observational experience.
AB  - We have used silicon vidicon tubes in a two-dimensional integrating imaging
      device at the telescope to obtain photometric images of astronomical objects. In
      this article we report on the performance of the imaging system we have
      experienced under actual observing conditions. The imaging system and the
      procedures we have devised to use it are described. Exposures reproduce to better
      than 0.05% of full scale intensity for each picture element. The response of the
      entire imaging system is linear with gamma = 1 for at least nearly 5 orders of
      magnitude to within at least 0.44% of full scale intensity and probably much
      better. Images made through the telescope of extended sources agree
      photometrically with photomultiplier measurements to about 1%. Photometry of
      stars reproduces to better than 0.5%.

PMID- 20154844
TI  - Experimental technique of dc induced SHG in liquids: measurement of the
      nonlinearity of CH(2)I(2).
AB  - The experimental technique of dc electric field induced second harmonic
      generation, which is used to measure the magnitudes and signs of the molecular
      hyperpolarizabilities of organic liquids, is described. Using this method we have
      determined the macroscopic third-order nonlinearity of CH(2)I(2) (which is
      dipolar) as well as the microscopic third-order nonlinearity for a single
      molecule.

PMID- 20154845
TI  - Nonlinear optimization; some applications to colorant formulations.
AB  - A nonlinear optimization technique is applied to metameric and spectral color
      matchings. This technique proves very powerful in always obtaining feasible
      solutions and smaller errors, particularly in the high reflectance region.

PMID- 20154846
TI  - Patent.
AB  - 3,663,084; 3,666,347; 3,667,827; 3,669,530; 3,679,294; 3,711,192; 3,713,740;
      3,722,982; 3,737,214; 3,748,021; 3,749,489; 3,752,591; 3,740,120; 3,741,630;
      3,743,385; 3,743,387; 3,746,428; 3,748,015; 3,748,020; 3,756,697; 3,761,157;
      3,761,158; 3,762,801; 3,764,209; 3,783,764; 3,783,765; 3,784,277; 3,788,735;
      3,788,749; 3,790,256; 3,790,257; 3,791,713; 3,814,496; 3,814,504; 3,815,974;
      3,817,603; 3,823,999; 3,826,911; 3,827,059; 3,827,778; 3,827,785; 3,832,035;
      3,832,037; 3,833,283; 3,845,308;

PMID- 20154848
TI  - Applied optics of optics and opticists.

PMID- 20154847
TI  - Birefringent coupler for integrated optics: comment.

PMID- 20154849
TI  - Circular polarization in certain laser and holography applications.

PMID- 20154850
TI  - Area heterodyne optical detection of acoustic holograms.

PMID- 20154851
TI  - Mapping of noiselike sound sources with acoustical holography.

PMID- 20154852
TI  - Magnetooptic effects in garnet thin film wave-guides.

PMID- 20154853
TI  - Mode selective filtering by a coupling mechanism between glass fiber and thin
      film slab waveguide: erratum.

PMID- 20154854
TI  - Conical axicons used as optical polar everters.

PMID- 20154855
TI  - MTF of a 210-70-mm fiber-optic output x-ray image intensifier tube.

PMID- 20154856
TI  - Concurrent display of multiple functions.

PMID- 20154857
TI  - Thermography in microwave holography.

PMID- 20154858
TI  - Refractive indices of powdered materials and materials with nonspecularly
      reflecting surfaces: a simple method of determination.

PMID- 20154859
TI  - Photometer calibration problem for extended astronomical sources.

PMID- 20154860
TI  - Power collection reduction by mirror surface nonflatness and tracking error for a
      central receiver solar power system.
AB  - The effects of random waviness, curvature, and tracking error of plane-mirror
      heliostats in a rectangular array around a central-receiver solar power system
      are determined by subdividing each mirror into 484 elements, assuming the slope
      of each element to be representative of the surface slope average at its
      location, and summing the contributions of all elements and then of all mirrors
      in the array. Total received power and flux density distribution are computed for
      a given sun location and set of array parameter values. Effects of shading and
      blocking by adjacent mirrors are included in the calculation. Alt-azimuth
      mounting of the heliostats is assumed. Representative curves for two receiver
      diameters and two sun locations indicate a power loss of 20% for random waviness,
      curvature, and tracking error of 0.1 degrees rms, 0.002 m(-1), and 0.5 degrees ,
      3sigma, respectively, for an 18.2-m diam receiver and 0.3 degrees rms, 0.005 m(
      1), and greater than 1 degrees , respectively, for a 30.4-m diam receiver.

PMID- 20154861
TI  - Solar energy: the physics of the greenhouse effect.
AB  - For practical reasons, it is likely that low-temperature solar collectors have a
      more immediate future than high-temperature or photovoltaic generation of
      electricity. This paper discusses the physics of bare and covered flat-plate
      collectors. The greenhouse effect is the result of reducing convection to the
      point that radiation trapping becomes important. Nevertheless, at collector
      temperatures within 20-30 degrees C of ambient, convection from the collector
      surface is so important that a special absorber with low ir emissivity may be no
      more efficient than a good, black absorber. At higher temperatures, selective
      absorbers are desirable. In the low temperature range, collection efficiency can
      be kept well over 80%, but falls rapidly with increasing collector temperature.
      This suggests that solar power may see early application in conjunction with heat
      pumps for heating and air conditioning.

PMID- 20154862
TI  - Stationary concentrating reflector cum tracking absorber solar energy collector:
      optical design characteristics.
AB  - This article presents an analysis of the optical design characteristics of a
      stationary reflecting/tracking absorber solar energy collector. This type of
      collector consists of a segment of a spherical mirror placed in a stationary
      position facing the sun, but having a linear absorber that can track the image of
      the sun by a simple pivoting motion about the center of curvature of the
      reflector. The optical characteristics of this system and the axial variation of
      its concentration ratio are developed to provide information for the engineering
      design and sizing of this type of solar energy collector system.

PMID- 20154863
TI  - Resonant fluorescent scattering of solar radiation by the fourth positive band
      system of CO.
AB  - The resonant fluorescent scattering equations for a diatomic molecule are
      developed as a function of temperature, column density, and optical thickness of
      absorbing rotation lines. The equations are solved numerically for absorption of
      solar vacuum uv radiation by the carbon monoxide fourth positive band system.
      Saturation column densities are determined and computer spectra are presented. It
      is shown that at high column densities, fluorescent scattering of the solar Lyman
      a line by the (14,0) band constitutes a significant portion of the total
      absorption.

PMID- 20154864
TI  - Numerical study of the scattered electromagnetic field inside a hollow dielectric
      cylinder. 1:Scattering of a single beam.
AB  - The field structure and the total energy inside a thin hollow lossless dielectric
      cylinder have been studied numerically for normal incidence of collimated TM
      waves. The dependence of these quantities on the optical thickness and the inner
      radius of the cylinder and on the refractive index of the cylinder material has
      been discussed. It has been shown that optimization of the various parameters may
      lead to a localized peak of high relative irradiance and also a high
      concentration of energy inside the cylinder.

PMID- 20154865
TI  - Numerical study of scattered electromagnetic field inside a hollow dielectric
      cylinder. 2: Scattering of two phasematched beams.
AB  - The structure of the scattered field inside a hollow lossless dielectric cylinder
      in the case of two incident TM waves has been discussed. Results are given for
      the case of opposite directions of incidence, under positive and negative phase
      matched conditions of two beams of equal amplitude. It has been shown that so far
      as high irradiance over a small region is concerned, the effective gain is less
      than that of the case of a single incident beam. However, the advantage here is
      the symmetry of the field distribution.

PMID- 20154866
TI  - Light scattering from unclad fibers: ray theory.
AB  - Information contained in the position of the peaks of backscattered light
      intensity from an unclad fiber, with laser light incident at right angles to the
      fiber axis, is utilized to determine the parameter b/lambda (b = fiber radius,
      lambda free space wavelength). For known laser wavelength the fiber diameter can
      thus be determined. The theory is based on an approximate ray analysis and is
      compared with the results of the exact wave theory. Good agreement is obtained.
      The accuracy of this procedure may vary between 1% and 10%.

PMID- 20154867
TI  - Modes in fiber optical waveguides with ring index profiles.
AB  - Calculations have been made of mode properties of optical fibers with ring index
      profiles. Three idealized profiles with regions of depressed index on axis were
      chosen for study. The quantities of interest are the propagation constant for
      various modes, the group delay, and the near and far field mode patterns. Near
      and far field patterns are compared with Gaussian TEM laser modes. The results
      are particularly relevant to studies of nonlinear interactions in fiber
      waveguides.

PMID- 20154868
TI  - Mode conversion coefficients in optical fibers.
AB  - A simple method has been devised for the experimental determination of mode
      conversion coefficients in multimode fibers and involves only the observation of
      the far-field output as the angle of incidence of a collimated input beam is
      changed. The normalized mode coupling coefficient in a liquid-core fiber is D = 3
      x 10(-6) rad(2) m(-1) and increases by as much as a factor of 10 when transverse
      pressure is applied. Values some 2 orders of magnitude larger are found in glass
      core fibers. There is good agreement between the theory presented and experiment.

PMID- 20154869
TI  - Launching efficiencies of the HE(1m) modes in a selffocusing optical fiber
      waveguide.
AB  - The launching efficiencies of the HE(1m) modes and the over-all launching
      efficiency are calculated for the cases in which a self-focusing optical fiber is
      excited axially by a TEM(0n) beam mode or by a beam consisting of several beam
      modes. It is shown that, when the fiber is excited by a TEM(00) mode whose spot
      size s is very large compared with the characteristic spot size s(0) of the
      fiber, the HEM(1m) modes are almost equally excited and that, if s is matched to
      s(0), the over-all launching efficiency is nearly 100%. The over-all launching
      efficiency as well as the launching efficiencies of the HE(1m) modes decrease
      considerably when the fiber is excited by a beam containing the TEM(01) mode that
      is out of phase with the TEM(00) mode. The effect of the off-axis excitation by a
      TEM(00) mode on the over-all launching efficiency is also examined.

PMID- 20154870
TI  - Visualization of traveling acoustic fields.
AB  - The visualization of traveling acoustic waves is achieved by means of acoustic
      stroboscopy. The limitations of the technique, interpretation of results,
      frequency range, and optical noise are reviewed. Two methods of noise reduction
      are studied: spatial filtering and holography. Optical holography of acoustic
      fields is also shown to offer the best advantages among the various methods of
      visualization outlined here.

PMID- 20154871
TI  - Fluid mechanical light guide.
AB  - It is shown that a beam of light can be deflected continuously through large
      angles along a curved path using the gas flow from a convergent-divergent nozzle
      sector whose throat lies on the arc of a circle. The amount of deflection depends
      on the included angle of the nozzle sector and on the density gradients created
      by the expanding gas flow. For a 360 degrees included angle the beam can in
      principle be bent into a closed path with a radius of the order of a few tens of
      centimeters: Nozzle sectors with included angles of 30 degrees and 180 degrees
      are studied both theoretically and experimentally. It is demonstrated that a well
      defined region exists in the flow wherein light rays are trapped in near-circular
      paths whose radii are close to the radius of the nozzle throat. The trapping
      region in effect constitutes a curved light guide. Very low light losses are
      predicted and measured, even for large deflections. Using nitrogen at a
      stagnation pressure of 110 atm as the working fluid, a laser beam is deflected as
      much as 180 degrees with a transmission approaching 100%.

PMID- 20154872
TI  - Open beam waveguides: theory.
AB  - The propagation of an electromagnetic wave through an open beam waveguide is
      theoretically investigated in the case where the guiding elements are not
      inserted in an absorbing screen. Numerical results are derived for the dielectric
      frame beam waveguide. The low loss per cell of such a waveguide and the existence
      of a quasi-repetitive field configuration are explained by the presence of an
      internal caustic surface, supported by the frames, bounding the axial portion of
      the beam. The finiteness of the transverse width of the frames and the absence of
      any outer screen suggest the formation of an external caustic surface, which is
      closer to the internal one the narrower the frames are. Knowledge of the features
      of the caustic due to each single frame is of help in the design of the low-loss
      beam waveguides with prescribed characteristics.

PMID- 20154873
TI  - GaAs optical waveguide structures at 10.6-microm wavelength.
AB  - A comparison of GaAs/n(+)GaAs, GaAs/GaAsP, and GaAs/AlGaAs waveguide structures
      is presented. Their fabrication processes and their transmission properties at
      10.6-microm wavelength are described. The loss due to the free carrier absorption
      of the substrate is analyzed. Experimentally, an attenuation rate of 2 dB/cm in a
      single mode (~7 microm) GaAs/GaAsp waveguide with a maximum dimension of the
      order of 7 cm has been achieved.

PMID- 20154875
TI  - Temperature and pressure effects on pressure-scanned etalons and gratings.
AB  - Various factors affecting the performance of pressure-scanned etalon and grating
      spectrophotometers are examined. The mechanical properties of the etalon plate,
      etalon spacer, and grating substrate materials are sometimes important, as is the
      temperature dependence of the spring constant for the etalon holder springs. The
      advantage to be gained etalon holder. from invar construction is usually
      negligible for a properly designed.

PMID- 20154874
TI  - Measurements of standing waves and the absorption coefficients of Various
      materials with surface electromagnetic waves on Al.
AB  - The first measurements of the absorption coefficient of materials via surface
      electromagnetic wave (SEW) techniques are reported. By simply laying samples on a
      metal sheet on which SEW were passing, the transmittances and absorption
      coefficients of the sample have been determined. These measurements were made at
      microwave frequencies, but the general techniques are applicable over the entire
      frequency range from microwaves into the near ir. Solid samples were used in
      these measurements, but liquid or gases could also be studied by this new easy-to
      use technique. Comments about the applicability of the technique to very thin
      samples are made. Another result reported is the existence of different
      propagating SEW modes as a function of the height of a sample (film thickness)
      measured from the metal-sample interface to the top of the sample at the sample
      vacuum interface above.

PMID- 20154877
TI  - Interferometry of strongly refracting axisymmetric phase objects.
AB  - Inversion of measurements of optical pathlength through strongly refracting,
      radially symmetric phase objects, such as plasmas, is discussed. An exact
      inversion scheme, based upon methods originally applied in seismology is
      developed and applied to interferometry. It is shown that Abel inversion, which
      assumes that the probing rays are straight lines, yields rather accurate results
      if the interferogram is formed with appropriate imaging.

PMID- 20154876
TI  - Space-invariant achromatic grating interferometers: theory.
AB  - A general analysis of an n-grating interferometer under various conditions of
      illumination is presented, where n = 1,...,4. Conditions for fringe localization
      and effects of misalignment are given. The lesser known phenomenon of the imaging
      of a grating by a second grating is described from which the fringe forming
      capacity of multiple-grating interferometers stems; this can occur regardless of
      the coherence of the source.

PMID- 20154878
TI  - Interferometer for measuring power distribution of ophthalmic lenses.
AB  - The use of a lateral shear interferometer in measuring the power variation of
      ophthalmic lenses is described and demonstrated. It is shown that an appropriate
      lateral shear interferometer directly measures the power variation of an
      ophthalmic lens. If the ophthalmic lens has a toric surface, the power for each
      axis can be measured separately. Individual surfaces can be tested, as well as
      the whole lens or the different segments of a multifocal lens. The sensitivity of
      the test can be selected by varying the amount of lateral shear. Because of the
      demonstrated simple relationship between fringe spacing and dioptric power,
      qualitative examination of the fringes has proved a useful adjunct to
      conventional quality control methods.

PMID- 20154879
TI  - OTF measurements with a white light source: an interferometric technique.
AB  - The use of lateral shear interferometers for measuring the optical transfer
      function of an optical system for a white light source is investigated. It is
      shown that grating lateral shear interferometers fulfill the requirements
      necessary to perform measurements of both the optical transfer function and the
      optical coherence function for a white light source. Several possible grating
      lateral shear interferometers are described.

PMID- 20154880
TI  - Michelson interferometer for detection of fast displacements of less than a
      quarter-wave over small areas.
AB  - A modified Michelson interferometer is described that allows calibration and
      measurement simultaneously. The method is used to detect displacements down to 1
      nm with a time resolution of 40 nsec. These values are close to theoretical
      resolution limits for the experimental arrangement. The probing beam is focused
      onto the investigated sample, allowing measurements with a lateral resolution of
      1.5 microm. The method has been applied to investigate the deformation behavior
      of pulsed diode lasers.

PMID- 20154881
TI  - Remote vibration measurement of rough surfaces by laser interferometry.
AB  - A He-Ne laser interferometer employing a focusing telescope is used remotely to
      measure transient longitudinal displacements of rough surfaces by monitoring the
      resulting Doppler shift of the backscattered light. The feasibility and accuracy
      of this technique are considered theoretically relative to laser output, range,
      telescope aperture, sensor efficiency, bandwidth, noise, surface characteristics,
      and coherence. The technique was successfully demonstrated on various test
      surfaces at distances up to 100 m using an unstabilized 4-mW laser, a 15-cm
      reflector telescope, and a PIN photodiode.

PMID- 20154882
TI  - Absorption and excitation spectra of fluorescently brightened fabrics.
AB  - A method of measuring the reflectance and corrected excitation spectra of
      fluorescently brightened wool fabrics using a spectrofluorometer is described.
      From the reflectance spectra the fraction of incident radiation absorbed by the
      fluorescent brightener (FBA) on the fabrics was calculated, and it was shown that
      these absorption values differed significantly from the excitation spectra, and
      therefore the two spectra could not be regarded as interchangeable. The ratio of
      the excitation and absorption values indicates the relative fluorescence
      efficiency, and this ratio was shown to vary significantly with wavelength of
      excitation and concentration of FBA.

PMID- 20154883
TI  - One-dimensional photon-counting detector array for use at EUV and soft x-ray
      wavelengths.
AB  - The performance of a one-dimensional photon-counting detector array based on
      microchannel array plates has been evaluated in the laboratory over the
      wavelength range from 461 A to 1216 A. The output charge pulses from a set of
      cascaded microchannel array plates were collected on a proximity-focused anode
      array consisting of sixty-four linear electrodes 1.3 mm in length and 25 microm
      in width, set on 50-microm centers. Although the dynamic range of the detector
      array was severely limited by ion-feedback effects in currently available
      microchannel array plates, the theoretical spatial resolution of 50 microm was
      achieved with a detection efficiency at wavelengths below 800 A equal to that of
      a conventional channel electron multiplier.

PMID- 20154884
TI  - Magnetic electron multipliers: efficiency changes.
AB  - During the mission of AEROS-A satellite the recorded calibration data exhibited a
      strong variation of the magnetic electron multiplier efficiency. Drastic changes
      do correlate with temperature; however, a clear separation of the temperature
      effect cannot be derived from the measurements. In space they have been impeded,
      e.g., by long-term efficiency changes, while in the laboratory ion feedback and
      other effects interfered with the measurements. The results affect the design of
      future space experiments especially for solar XUV measurements.

PMID- 20154885
TI  - Averaging spheres without target.
AB  - The design of averaging spheres without internal target is described. The
      performance of such spheres is analyzed theoretically and tested experimentally.
      In a final design, an efficiency of 40% is achieved for visible and near-uv
      wavelengths. The averaging effectiveness is characterized by signal variations of
      the order of 1 part in 10(4) for beam displacements of several 0.1 mm.

PMID- 20154886
TI  - Combined reflection and transmission thin-film ellipsometry: a unified linear
      analysis.
AB  - A scheme of combined reflection and transmission ellipsometry on light
      transmitting ambient-film-substrate systems is proposed and the required sample
      design and instrument operation are investigated. A comparative study of the
      sensitivity of external and internal reflection and transmission ellipsometry is
      carried out based on unified linear approximations of the exact equations. These
      approximations are general in that an arbitrary initial film thickness is
      assumed. They are simple, because a complex sensitivity function is introduced
      whose real and imaginary projections determine the psi (Psi) and delta (Delta)
      sensitivity factors. Among the conclusions of this paper are the following. (1)
      External reflection ellipsometry near the Brewster angle of a transparent ambient
      substrate system is extremely sensitive to the presence of very thin interfacial
      films. For example, films as thin as 10(-5) A of gold are readily detectable on
      glass substrates at an angle of incidence 0.3 degrees below the Brewster angle,
      assuming a measuring wavelength of 5461 A with an ellipsometer of 0.05 degrees
      precision. (2) The formation of thin nonabsorbing films at the interface between
      transparent ambient and substrate media is not detectable, to first order, as a
      change in the ellipsometric angle Psi by either internal or external reflection
      or transmission ellipsometry. (3) The film-detection sensitivity of transmission
      ellipsometry increases monotonically with angle of incidence. (4) For each angle
      of external incidence there is a corresponding angle of internal incidence that
      leads to the same values of the reflection and transmission sensitivity
      functions. These angles are interrelated by Snell's law. (5) The ranges of
      validity of the linear approximation in reflection and transmission ellipsometry
      are comparable. The case of total internal reflection ellipsometry may lead to
      strong nonlinear behavior of Psi and Delta as functions of the film thickness in
      the range below 0.05 of the wavelength of light.

PMID- 20154887
TI  - High-path-difference optical compensator: its use in the observation of solid
      solid phase transformations.
AB  - A simple experimental method has been developed for permitting the visual
      observation of subtle structural transformations in transparent birefringent
      solids. The method makes use of an optical compensator with a large path
      difference in conjunction with standard equipment for polarized light microscopy.
      This method has been applied successfully in the observation of subtle phase
      transformations in p-diiodobenzene and in phenanthrene.

PMID- 20154888
TI  - Mesh-based semitransparent photocathodes.
AB  - Semitransparent photocathodes consisting of vacuum-deposited layers of CsI on
      electroformed nickel meshes with 40 and 60 lines/mm spacing have been
      investigated for applications in vacuum-ultraviolet electronic imaging devices.
      These photocathodes are found to have about half the quantum yield of an opaque
      CsI photocathode, but a factor of 2 to 3 greater quantum yield than a
      conventional semitransparent CsI photocathode. The limitations of window
      materials on short-wavelength spectral response, and their disadvantages in an
      energetic charged-particle environment, are eliminated. Unlike conventional
      opaque photocathodes, the mesh photocathodes can be used interchangeably with
      conventional semitransparent photocathodes in a wide variety of electronic
      imaging devices. Tests of mesh photocathodes in laboratory electrographic cameras
      indicate that best results for most applications are obtained if the output
      electron image has a somewhat poorer resolution than that corresponding to the
      mesh spacing.

PMID- 20154889
TI  - Rapid-scanning laser receiver.
AB  - A random-access rapid-scanning laser receiver concept utilizing the acoustooptic
      effect and suitable for applications from the near uv through the long-wave ir
      region was designed and demonstrated in the field at a 10.6-microm laser radar.
      Experimental results demonstrating its utility for image detection, radar,
      atmospheric optics measurements, and vibration isolation are presented.

PMID- 20154890
TI  - Emulsion thickness and space variance: combined effects in Vander Lugt optical
      correlators.
AB  - Previous studies have shown-that the intensity of the correlation peaks in Vander
      Lugt optical correlators can change with the position of the object because of
      emulsion thickness effects. In this paper, it is shown that the intensity
      variations are caused by a combination of thickness effects and a position
      dependent frequency cutoff due to space variance of the optical processor.
      Experiments showing the global effect, as well as experiments showing each effect
      acting alone, have been performed.

PMID- 20154891
TI  - Spatial filtering and image positive-negative reversal.
AB  - A generalized analysis of spatial filtering of object transparencies modulated by
      (TV) raster lines has been developed from which various particular cases and also
      the limits and approximations of the processes appear naturally. It can be seen
      that the positive-negative reversal of the filtered image depends upon the nature
      of the modulating lines (opaque or clear) and also on the order of the Fourier
      spectrum that forms the image. The same analysis (one dimensional) can also
      explain, in principle, the behavior of the filtered images from half-tone
      transparencies. The experimental results reported support the analysis.

PMID- 20154892
TI  - Error rates in computer-generated holographic memories.
AB  - A procedure for predicting the error rates of a computer-generated holographic
      memory with general transform domain quantization error is developed. The
      kinoform, ROACH, detour phase binary hologram, and generalized detour phase
      binary hologram are compared on the basis of error rates and encoding efficiency.
      Error rates predicted by the analysis are compared with those obtained by
      computer simulation.

PMID- 20154893
TI  - Noise reduction by continuous addition of subchannel holograms.
AB  - A new and convenient technique for reducing both speckle and coherent noise in
      holographic imagery is described with supporting experimental results. Its
      advantages and disadvantages have been mentioned in the context of other known
      techniques.

PMID- 20154894
TI  - Tunability characteristics of waveguide CO(2) lasers with internal etalons.
AB  - We investigate the possibility of increased tuning range of waveguide CO(2)
      lasers by using a longer discharge and a tilted intracavity etalon as axial mode
      selector. Taking into account etalon losses, the tuning range was calculated as a
      function of laser gain, pressure, and discharge length. Improvements depend
      strongly on the index of refraction and the absorbtivity of the etalon material.
      The comparison with a length-restricted laser without mode selection shows that
      the use of a CdTe etalon in a laser with 25-cm active length could increase the
      tuning range from 1.5 GHz to 2.2 GHz. However, an air etalon reduces the
      bandwidth due to higher tilting losses.

PMID- 20154895
TI  - Laser based on electrochemiluminescence.
AB  - The specific points raised here augment the full paper on this same subject by
      Measures [Appl. Opt. 13, 1121 (1974)]. In support of the feasibility of such a
      laser, an electrochemiluminescent system with o(ecl) ~0.2 is cited from the
      literature (vs o(ecl) ~1.4 x 10(-2)); and in relation to the feasibility
      calculations, the incompleteness of the Feldberg model is noted. Various other
      topics are also discussed.

PMID- 20154896
TI  - Rotational relaxation in a line-selected continuous HF chemical laser.
AB  - Rotational relaxation effects in a cw chemical laser amplifier or a line-selected
      oscillator are examined in terms of a simple analytical model. Three rotational
      levels in each vibrational level of the lasing transitionare taken to have finite
      rotational relaxation rates. The results.indicate the effects are likely to be
      significant, lowering the available power and leading to an optimum level of the
      line intensity for maximum power output, apart from consideration of optical
      losses at mirrors, windows, etc. While the model accounts for Deltaj = +/-1
      transitions only, the collisional transition probability was augmented in the
      computations in an attempt to provide high estimates for the rotational
      relaxation rates, including factors such as Deltaj > 1 transitions.

PMID- 20154897
TI  - Earth laser beacon sensor for earth-oriented geosynchronous satellites.
AB  - Geosynchronous satellites are often required to maintain accurately their
      orientation with respect to a selected point at the earth surface. Precise
      attitude determination of these satellites may be achieved using a laser beacon
      from ground to the satellite as a directional reference. Four simple
      implementations of this principle are analyzed, and the influence of the cloudy
      atmosphere on the laser beacon and, therefore, on the accuracy of the method is
      discussed. All-weather operation is not possible; for normal cloudiness
      conditions, however, two analyzed systems (pulsed Nd:YAG laser with
      photomultiplier and CO(2) laser with cryogenic detector) appear to be feasible.

PMID- 20154898
TI  - Focusing crystal polarimeter designed for x-ray polarimetry: construction and
      performance.
AB  - A method for the construction of a graphite crystal polarimeter designed for
      measuring linear polarization of x-ray continuum sources is described. The
      dependence of reflected intensity upon the polarization direction of the incident
      beam at Bragg angles of 45 degrees is used to measured the polarization. The
      particular instrument described was designed for a satellite x-ray polarimeter.
      By using a focusing parabolic surface instead of a nonfocusing flat crystal, the
      signal to background ratio is improved by a factor of 30 as compared to a flat
      crystal polarimeter of the same effective area. The focusing properties of the
      reflector were tested both optically and with x rays. The performance of the
      instrument as a polarimeter was tested with a continuum x-ray source of small
      polarization, which was independently measured by a single flat crystal
      polarimeter. The agreement between the two measurements is excellent, indicating
      that the instrument can measure polarizations as low as 0.3%.

PMID- 20154900
TI  - Patents.
AB  - 3,703,330; 3,848,964; 3,848,965; 3,848,967; 3,848,968; 3,848,969; 3,848,971;
      3,849,738; 3,848,972; 3,850,502; 3,850,507; 3,850,509; 3,851,318; 3,851,952;
      3,851,953; 3,853,387; 3,854,793; 3,856,385; 3,856,386; 3,858,124; 3,858,201.

PMID- 20154901
TI  - Fiber optic faceplate excited Ruticon color image reproduction system.

PMID- 20154902
TI  - Optical measurements of liquid film profile and dynamic contact angle.

PMID- 20154903
TI  - Advances in bleaching methods for photographically recorded holograms: comments.

PMID- 20154904
TI  - Selection of a single pulse from a mode-locked laser using avalanche transistors.

PMID- 20154905
TI  - Applied optics of optics and opticists.

PMID- 20154906
TI  - Optical effects of the 1974 stratospheric dust cloud.

PMID- 20154908
TI  - Patents.
AB  - 3,813,555; 3,814,497; 3,814,498; 3,821,549; 3,822,927; 3,822,928; 3,837,744;
      3,839,684; 3,843,231; 3,841,730; 3,844,660; 3,846,715.

PMID- 20154907
TI  - Optical activities in industry.

PMID- 20154909
TI  - Laser resonators with polarizing elementse-eigenstates and eigenvalues of
      polarization: addendum.

PMID- 20154910
TI  - Ocular tissue damage due to ultrashort 1060-nm light pulses from a mode-locked
      Nd:glass laser.

PMID- 20154911
TI  - Glass inhomogeneity.

PMID- 20154912
TI  - Television based Fourier holographic system: comments.

PMID- 20154913
TI  - Time response of NBS windowless XUV radiometric transfer standard detectors.

PMID- 20154914
TI  - Backscattered short pulse response of surface waves from dielectric spheres:
      comment.

PMID- 20154915
TI  - Real-time particle sizing: increasing the capability of the instantaneous
      scattered intensity-ratio technique.

PMID- 20154916
TI  - Test colors for specifying color reproduction.

PMID- 20154917
TI  - Unit color-difference figures derived from the proposed CIE 1976 L*a*b* space:
      erratum.

PMID- 20154918
TI  - Machining of optics: an introduction.
AB  - This paper introduces machining of optics, presenting some of the history of
      machining progress, critical machining variables, material and geometrical
      capabilities, and some new results on optical evaluation of machined surfaces. A
      most significant development is electroplating of materials that are otherwise
      not presently machinable. For example, molybdenum has been electroplated with
      silver or gold and then successfully diamond turned. Research and development
      ideas for future machining studies will be briefly discussed.

PMID- 20154919
TI  - Tool feed influence on the machinability of CO(2) laser optics.
AB  - Influence of tool feed on reflectivity of diamond-machined surfaces was evaluated
      using materials (gold, silver, and copper) from which CO(2) laser optics are
      primarily produced. Fifteen specimens were machined by holding all machining
      parameters constant, except tool feed. Tool feed was allowed to vary by
      controlled amounts from one evaluation zone (or part) to another. Past experience
      has verified that the quality of a diamond-machined surface is not a function of
      the cutting velocity; therefore, this experiment was conducted on the basis that
      a variation in cutting velocity was not an influencing factor on the
      diamondturning process. Inspection results of the specimens indicated that tool
      feeds significantly higher than 5.1 micro/rev (200 microin./rev) produced
      detrimental effects on the machined surfaces. In some cases, at feeds as high as
      13 microm/rev (500 microin./rev), visible scoring was evident. Those surfaces
      produced with tool feeds less than 5.1 microm/rev had little difference in
      reflectivity. Measurements indicat d that their reflectivity existed in a range
      from 96.7% to 99.3% at 10.6 microm.

PMID- 20154920
TI  - Electroplating application to the fabrication of optics.
AB  - The advent of high-power-density lasers has placed new requirements on optical
      reflectors. In particular, there is a need for surfaces of high purity metals
      that are fee of minute defects, such as inclusions and voids, which can lead to
      damage at low-power densities. Electroplating has been found to be a viable
      method of providing the metal for such surfaces.

PMID- 20154921
TI  - Residual surface roughness of diamond-turned optics.
AB  - The residual surface roughness of diamond-turned optics is expected to contain
      significant periodic components. The optical properties of such surfaces are
      explored as a special case of Rayleigh-Rice vector scattering theory applied to
      periodic roughness with vertical amplitudes much smaller than the wavelength of
      light. Expressions are given for the interpretation of differential-scatter,
      total-integrated-scatter, reflectometry, and ellipsometric measurements in the
      limit of a highly conducting. surface. In general, such measurements give varying
      degrees of information about the two-dimensional power spectral density of the
      surface roughness within the nominal range from the wavelength of light to the
      diameter of the probing beam spot. Such information may be useful for the
      practical characterization of mirror surfaces.

PMID- 20154922
TI  - Roughness characterization of smooth machined surfaces by light scattering.
AB  - Characterization of surface roughness has generally been limited to rms deviation
      from the mean and occasionally the autocorrelation length. By considering the
      surface to be a superposition of many sinusoidal gratings, the surface spectral
      density function (SDF) has been calculated from measurements of the light
      scattered out of a reflected He-Ne laser beam. By rotating the sample, the SDF
      can be found for anisotropic surfaces (such as machined surfaces). The SDF allows
      examination of roughness as a function of spatial frequency, which is important
      for many applications. Interferometric and scattering results are compared for a
      rough (350-Arms) machined surface, and finally a smooth (50-Arms) diamond
      machined surface is characterized.

PMID- 20154923
TI  - Ion polishing of copper: some observations.
AB  - The change in absorptivity at 10.6 microm of copper samples, at various stages of
      polishing including ion polishing, is reported. The ion polishing apparatus is
      also described; it employs a low energy Xe ion beam incident at a glancing angle
      to maximize the removal rate while minimizing ion penetration and damage. The
      sample to be polished is rotated and the beam scanned across the surface to
      produce uniform removal of material. Starting with single crystal copper that had
      been mechanically polished and by using combinations of ion polishing and vacuum
      annealing, the absorptivity, determined by calorimetry, was reduced from 0.92% to
      0.76%. Although optical figure and scatter were not monitored, SEM pictures show
      that the surface features become smoother with ion polishing. A similar
      experiment was performed on a single crystal copper sample that had been
      electropolished, and the combination of ion polishing and annealing lowered the
      absorptivity from 0.97% to 0.89%.

PMID- 20154924
TI  - Polishing of supersmooth metal mirrors.
AB  - This work has resulted in clarifying the fabrication technology that is required
      for high energy 10.6-microm laser programs now underway. Polishing and coating
      techniques for metallic substrates were developed, and the deposition of metallic
      coatings to reproducibly create metal mirror surfaces with low absorptance at a
      wavelength of 10.6 microm was investigated. The basic task was one of expanding
      and transferring to metal substrates the technology developed by Bennett and
      Ashley for fused silica substrates. Metal substrates of molybdenum, TZM, and
      beryllium-copper were polished to a surface roughness of from 12 A to 15 A rms
      and overcoated with ultrahigh vacuum silver and gold. Absorption coefficients
      obtained were as low as 0.0064. The basic finishing techniques that are now
      employed are acid etch stress relieving and controlled grinding, modified
      conventional polishing techniques, sputtering of similar metallic film, and
      modified conventional polishing. Quantitative evaluations of the substrates were
      made with t e total integrated scatterometer (6328 A), photomicrograph studies,
      the newly developed fringes of equal chromatic order (FECO) interferometer, and
      the absolute calorimeter measurement.

PMID- 20154925
TI  - Nonlinear filtering in coherent optical systems through halftone screen
      processes.
AB  - Nonlinear filtering operations can be performed in coherent optical systems with
      the help of the halftone screen process. Theoretical and practical considerations
      regarding this type of system are presented. The use of these methods to achieve
      logarithmic filtering is emphasized. Applications to separation of multiplicative
      signals and noise, speckle noise reduction, and processing of radiographic images
      are considered. Experimental results are presented.

PMID- 20154926
TI  - Paraxial ray analysis of a cat's-eye retroreflector.
AB  - The cat's-eye retroreflector is a passive optical system consisting of a
      secondary mirror placed at the focal point of a primary lens. We analyze the
      cat's eye using the paraxial ray matrix approach. The position of the equivalent
      reflecting surface and the angular field of view of a realizable cat's eye are
      functions of the radius of curvature of the secondary mirror. The field of view
      is maximum for a secondary mirror with a concave radius of curvature equal to the
      focal length of the primary lens. We further derive the general dependence of
      retroreflection errors on misadjustment of the secondary mirror.

PMID- 20154927
TI  - Analysis of images by Hadamard optical transform.
AB  - The problems of developing an optical system to perform image Hadamard transforms
      are discussed. The method involves parallel-successive calculations of the
      elements of the matrix of spectral components resulting from the decomposition of
      an initial image into Walsh functions. The basic unit of the optical system
      realizing this method is an integrator representing a projecting optical system
      with defocusing in one of the directions. The procedure of the choice of the
      parameters of such a unit pulse response is described, and the experimental
      results are given. The matrix of 8 x 8 spectral components was calculated. The
      calculation error is equal to 1.5-2%. The possibilities of the suggested method
      for image coding are noted.

PMID- 20154928
TI  - Digital solid-state scan-converter with unusual display capabilities.
AB  - A digital solid-state scan-converter has been developed and used with an
      integrating silicon vidicon imaging system. The device will store a 256 x 256
      picture-element image indefinitely with a resolution of 32 gray levels. Various
      display modes are available. These include plots of intensity vs position, as
      well as direct images.

PMID- 20154929
TI  - SNR in optical velocimeters: effect of particle number density.
AB  - Measurements of SNR as a function of number density (n) were carried out
      employing a Differential Heterodyne Laser Doppler Velocimeter (DLDV) and a White
      Light Fringe Image Velocimeter (WFIV). These two techniques made it possible to
      investigate separately the coherent and incoherent scattering modes,
      respectively. It was observed that with the WFIV the SNR is proportional to n for
      n values corresponding to less than one particle in the probe volume. The SNR
      remains constant for large n values. In the case of the DLDV the SNR was always
      found to be proportional to n when the coherence condition was satisfied.
      Consequently, it is concluded that the DLDV signal results entirely from coherent
      scattering, even when the number of particles in the probe volume is as low as
      0.02 (the lower limit of the measurements).

PMID- 20154930
TI  - Tapered edge ridge waveguides for integrated optics.
AB  - We propose a tapered edge ridge (TER) waveguide as a flexible means for
      interconnecting devices in integrated optics. Since the guiding film itself is in
      the form of a ridge, the maximum acceptance angle can be very large. The tapered
      edges of the ridge help to make the scattering losses negligible. Our experiments
      with a tantulum oxide guide on a 7059 glass substrate show that scattering losses
      from the tapered edges are small if any. We have coupled light at 20 degrees to
      waveguide axis with light propagation occurring with no apparent loss from
      scattering at the edges. We have developed a theory that can be used to compute
      ray trajectories in the tapered regions and have devised an expression (similar
      to the critical angle in total specular reflection) for the maximum acceptance
      angle that happens to be approximately 42 degrees for our structure.

PMID- 20154931
TI  - Three-dimensional curved surface for integrated optics.
AB  - As an extension of our previous experimental and theoretical studies on
      homogeneous dielectric cylindrical surface or a single curved boundary on thin
      dielectric film as an optical waveguide, we study the behavior of a wave being
      guided by a conic or spherical surface. Experiments show that these surfaces
      cause the guided light to be deflected continuously toward the region with larger
      cross section, an effect that can be explained either by geometric optics or by
      wave equations. Possible applications of these surfaces in integrated optics are
      discussed.

PMID- 20154932
TI  - Externally mounted fibers for integrated optics interconnections.
AB  - A variety of input-output coupling problems remain central to the development of
      fiber and integrated optics communication systems. This paper discusses an
      externally mounted fiber consisting of a high index rectangular waveguide mounted
      on a larger low index support fiber. These fibers can be used to provide coupling
      between linear integrated optic guides and fibers or laser sources. Tapered
      (crossed-) couplers are discussed in this context, and a simple expression for
      their coupling efficiency is presented. Externally mounted fibers have been
      fabricated, and experimental efficiencies of 70% for fiber-fiber and integrated
      optic linear waveguide-fiber coupling obtained. unication systems. This paper
      discusses an externally mounted fiber consisting of a high index rectangular
      waveguide mounted on a larger low index support fiber. These fibers can be used
      to provide coupling between linear integrated optic guides and fibers or laser
      sources. Tapered (crossed-beta) couplers are discussed in this context, and a
      simp e expression for their coupling efficiency is presented. Externally mounted
      fibers have been fabricated, and experimental efficiencies of 70% for fiber-fiber
      and integrated optic linear waveguide-fiber coupling obtained.

PMID- 20154933
TI  - PLZT electrooptic shutters: applications.
AB  - This paper describes advances in the development of several electrooptic shutter
      devices utilizing the quadratic electrooptic effect of lead lanthanum zirconate
      titanate (PLZT) ceramic wafers. Aperture sizes utilized in these PLZT devices
      ranged from 25 microm to 0.25 m. Practical applications of the shutters discussed
      in this paper include eye protection in military and industrial applications, a
      goggle-type device with dual synchronously operated PLZT shutters for use in a
      stereoscopic three-dimensional TV display, an electrically controlled variable
      density filter for use with vidicon tubes, a large-aperture photographic shutter
      for image motion compensation cameras, and a page composer for use in a
      holographic memory system.

PMID- 20154934
TI  - Mode calculations in unstable resonators with flowing saturable gain. 2: Fast
      Fourier transform method.
AB  - We present further calculations of the three-dimensional mode patterns and power
      outputs from a highpower gas-dynamic laser, including a nonuniform flowing,
      saturable gain medium plus index inhomogeneities (shocks) inside the laser. The
      calculations are carried out using a plane-wave or k-space expansion together
      with the fast Fourier transform. A new expanding-beam coordinate transform
      converts all diverging or converging sections of the resonator mode into
      equivalent collimated beam sections. The resulting FFT propagation code is
      significantly faster than earlier propagation codes using other eigenmode
      expansions.

PMID- 20154935
TI  - Active annular-beam laser autocollimator system.
AB  - An autocollimator using an axicon and a beam expander telescope to generate a
      12.5-cm. o.d. annular beam of helium-neon laser light with high (25:1) diameter
      to-width ratio has been developed. It is used with a two-axis,
      electromagnetically actuated mirror assembly to acquire automatically and
      maintain dynamically autocollimation from a nearby but separately mounted annular
      mirror. The servo system controls beam alignment even though angular vibratory
      motions of the annular mirror make it appear to tilt relative to the
      autocollimator as much as 7 mrad at frequencies below 300 Hz. This paper
      describes the optical system and the alignment sensing and control system.

PMID- 20154936
TI  - Helium-neon laser stabilized on iodine: design and performance.
AB  - A helium-neon laser operating at 633 nm was frequency stabilized on a hyperfine
      component of (127)I(2) with saturated absorption. The stability achieved was 2.5
      x 10(-12) at an averaging time of 400 sec. The frequency was reproducible to 5 x
      10(-11).

PMID- 20154937
TI  - Potential electronic transition chemical laser: parametric evaluation.
AB  - Through the utilization of a generalized computer code that calculates the
      minimum reactive branching ratio required for a species to display optical gain,
      a parametric study was performed to ascertain which properties of the electronic
      potential curves of a heteronuclear diatomic molecule have the greatest effect on
      the suitability of that molecule as a potential electronic transition laser. The
      results of this study demonstrate that diatomic systems separate into different
      classes when the question of the minimum required reactive branching ratio is
      confronted. This separation of molecular systems was translated through the use
      of compiled molecular constants into a determination of which vibrational-level
      distribution class is most favorable for specific heteronuclear diatomic
      molecules to display optical gain; potential laser candidates were pointed out.
      In addition, a generalized gain equation for electronic transitions heteronuclear
      diatomic molecules that takes into account both rotational and vibrati nal
      partitioning was derived.

PMID- 20154938
TI  - Atmospheric 10.6-microm absorption coefficient: dynamics.
AB  - The parameter of paramount importance to the propagation of an optical beam
      through a given medium is the absorption coefficient. For 10.6-microm beams, the
      absorption coefficient for dry air is established by the CO(2) population in the
      001 and 100 levels. The dynamics of such an absorption coefficient are examined
      in terms of upper and lower CO(2) level kinetics for both V-V and V-T
      interactions with other atmospheric molecular constituents, the radiation field,
      and the temperature changes due to V-T processes. The particular case studied is
      a pulse length in the V-V and V-T kinetics regime.

PMID- 20154939
TI  - Separation of dust and molecular scattering contributions to the lidar
      observation: a method.
AB  - A feasibility study is performed to further explore the potential of the lidar
      observation as a tool for the study of the molecular and dust structure of the
      atmosphere. A computerized model of observation and solution is used to
      demonstrate a specific multiwavelength technique for separating the molecular and
      dust components of the lidar sounding up to 30 km. The detection of a time
      dependent temperature wave at 13 km is simulated. The problem of observational
      error is also examined.

PMID- 20154940
TI  - Radiative transfer in the earth's atmosphere and ocean: influence of ocean waves.
AB  - The radiance in the earth's atmosphere and ocean is calculated for a realistic
      model including an ocean surface with waves. Individual photons are followed in a
      Monte Carlo calculation. In the atmosphere, both Rayleigh scattering by the
      molecules and Mie scattering by the aerosols as well as molecular and aerosol
      absorption are taken into account. Similarly, in the ocean, both Rayleigh
      scattering by the water molecules and Mie scattering by the hydrosols as well as
      absorption by the water molecules and hydrosols are considered. Separate single
      scattering functions are used which are calculated separately for the aerosols
      and the hydrosols from the Mie theory with appropriate and different size
      distributions in each case. The scattering angles are determined from the
      appropriate scattering function including the strong forwardscattering peak when
      there is aerosol or hydrosol scattering. Both the reflected and refracted rays,
      as well as the rays that undergo total internal reflection, are followed at the
      oceanc surface. The wave slope is chosen from the Cox-Munk distribution. Graphs
      show the influence of the waves on the upward radiance at the top of the
      atmosphere and just above the ocean surface and on the downward radiance just
      below the ocean surface as well as deeper within the ocean. The radiance changes
      are sufficient at the top of the atmosphere to determine the sea state from
      satellite measurements. Within the ocean the waves smooth out the abrupt
      transition that occurs at the edge of the allowed cone for radiation entering a
      calm ocean. The influence of the waves on the contrast between the sky and sea at
      the horizon is discussed. It is shown that the downward flux just below the
      surface increases with wind speed at all solar angles.

PMID- 20154941
TI  - Differences in Radiance: relative effects of temperature changes and emissivity
      changes.
AB  - Calculations are made for the relative effects of temperature change and
      emissivity change causing a change in radiance. These are done for the total
      radiation and the monochromatic radiation at the wavelength that maximizes the
      contrast. They are done for no background contribution, a uniform background, and
      a general, nonuniform background. The general result, subject to some of the
      details, is that for a 300 K ambient, changes in emissivity of 0.01 correspond to
      a temperature change of about 0.5 K.

PMID- 20154942
TI  - Efficient averaging spheres for visible and ultraviolet wavelengths.
AB  - On the basis of a theoretical analysis that identifies the design criteria for
      optimization of efficiency, an averaging sphere with a barium-sulfate target was
      constructed that has an efficiency of 80-90% in the visible. In spite of the
      decreased reflectance of the sphere walls in the uv, this sphere is still 30%
      efficient at 300 nm and, thus, can be used for near-uv work. For applications
      below 300 nm, a cell containing a fluorescent dye is placed inside the sphere in
      order to shift the incident radiation into the longer wavelength region in which
      the reflectance of the sphere walls is higher. The use of this fluorescent
      wavelength converter, which was designed so that the sphere remains usable in the
      visible, resulted in a sphere efficiency of about 20% in the region between 200
      nm and 300 nm and 50% in the visible. The averaging properties of these spheres
      were found to be adequate for high-accuracy photometric measurements.

PMID- 20154943
TI  - Planar germanium photodiodes.
AB  - Planar passivated germanium photodiodes have been developed whose useful response
      at 22 degrees C extends from 0.6 microm to 1.85 microm at a nominal operating
      voltage of 20 V. Typical characteristics at 22 degrees C are diode capacitance,
      100 pF/cm(2); rise and fall times, 10 nsec; leakage current, 2.5 mA/cm(2) ;
      D*(1.54 microm) approximately 2.5 x 10(10) cm/W/ radicalHz with a 3-dB frequency
      of ~45 MHz. Single and multiple element detectors ranging in size from 2 x 0.25
      mm(2) elements with 50-microm spacing between elements to 3-cm(2) quadrant
      detectors have been made successfully for operation at temperatures from 77 K to
      room temperature.

PMID- 20154944
TI  - Heterodyne detection: phase front alignment, beam spot size, and detector
      uniformity.
AB  - We consider the effects of signal and local oscillator phase front misalignment,
      beam spot sizes, and electric field distributions on heterodyne detection. The
      signal and local oscillator fields that we consider are various combinations of
      Airy, Gaussian, and uniform distributions. We show that the values of the beam
      radii that maximize the heterodyne SNR are sensitive to phase front misalignment
      and that the degradation with misalignment angle is somewhat less severe for Airy
      received signals than for uniform. We also prove that for small optical spot
      sizes and perfect alignment, the optimal ratio of local oscillator Gaussian l/e
      field radius to signal Airy F number is approximately 0.7lambda. We next consider
      the effects of nonuniform detector quantum efficiency. Simple examples show that
      quantum efficiencies averaged over the detector surface give only crude estimates
      of the sensitivity of a heterodyne system. For accurate estimates full account
      must be made of the electric field parameters and the detector re ponse at each
      point on its photosurface.

PMID- 20154945
TI  - Optimal optoacoustic detector design.
AB  - Optoacoustic detectors are used to measure pressure changes occurring in enclosed
      gases, liquids, or solids being excited by intensity or frequency modulated
      electromagnetic radiation. Radiation absorption spectra, collisional relaxation
      rates, substance compositions, and reactions can be determined from the time
      behavior of these pressure changes. Very successful measurements of gaseous air
      pollutants have, for instance, been performed by using detectors of this type
      together with different lasers. The measuring instrument consisting of radiation
      source, modulator, optoacoustic detector, etc. is often called spectrophone.In
      the present paper, a thorough optoacoustic detector optimization analysis based
      upon a review of its theory of operation is introduced. New quantitative rules
      and suggestions explaining how to design detectors with maximal pressure
      responsivity and over-all sensitivity and minimal background signal are
      presented.

PMID- 20154946
TI  - Resolution and stray light in near infrared spectroscopy.
AB  - The slit function at 1064 nm for a double monochromator spectrophotometer has
      been obtained with sufficient dynamic range to quantitatively account for the
      resolution and stray light over a wide range of resolutionv and absorbance
      levels. Conventional stray light tests are found to underestimate seriously that
      portion of the nearby stray light that most influences errors in ir absorbance
      determinations, and improved tests are suggested. A revision of the definition of
      stray light is suggested in order to minimize the variation of stray light with
      resolution. Convolutions of the observed slit functions with the transmittance
      function for the 1691-nm band of chloroform agree with observed absorbance
      measurements over a wide range of resolution and absorbance levels. The ratio of
      true to observed absorbance levels for chloroform is significantly less
      influenced by resolution than the literature, using triangular or Gaussian slit
      functions and Lorentzian absorbance functions, predicts.

PMID- 20154947
TI  - Double-beam high resolution Fourier spectrometer for the far infrared.
AB  - The construction and the performance of a double-beam Michelson-type Fourier
      spectrometer are described. The instrument covers a wavenumber range from 10 cm(
      1) to 450 cm(-1) with a maximum resolution of 0.025 cm(-1) and an accuracy of
      frequency within +/-0.001 cm(-1). The optical path difference is measured by
      means of an He-Ne gas laser. To illustrate the general performance of the
      instrument, the pure rotational spectra of H(2)O and CO have been recorded.

PMID- 20154948
TI  - Measurement of weak ir absorption with a tunable laser: the hydrogen S(2)(1) line
      strength.
AB  - A tunable laser light source has been used to obtain the intensity of the S(2)(1)
      hydrogen quadrupole line at ~8604.2 cm(-1). The result (0.0140 +/- 0.0007 cm(
      1)/km-amagat) is in excellent agreement with a previous determination as well as
      with ab initio calculations.

PMID- 20154949
TI  - Infrared interferometer with a scanned aperture.
AB  - A Twyman-Green interferometer operating at a 3.39-microm wavelength has been
      built in which the collimator aperture was scanned by a laser beam. The scanning
      was produced by reflecting the laser beam from a mirror supported by four
      piezoelectric elements and oscillated about two orthogonal axes. The radiation
      transmitted by the interferometer was measured by a stationary detector of small
      area. The complete system offers a cheap and efficient alternative to
      conventional ir interferometers.

PMID- 20154950
TI  - Diffraction corrections in radiometry: comparison of two different methods of
      calculation.
AB  - We have studied the effect of diffraction on the flux received by a detector
      located in the fully illuminated region cast by a circular aperture which is
      placed between a point source and the detector. This case was studied previously
      by Steel, De, and Bell, who have derived a diffraction correction formula based
      on an intensity distribution approximation due to Focke. We have derived a
      diffraction correction formula based on a different type of approximation. The
      corrections predicted by this formula are much greater than those predicted by
      Steel et al.'s formula. The validity of our formula and reasons for the
      discrepancy between the two methods are discussed; some supporting experimental
      evidence is presented. The case of complex radiation is discussed; it is shown
      that, under certain conditions, the calculation of diffraction cor rections is
      very simple.

PMID- 20154951
TI  - Ellipsometric method for separate measurements of n and d of a transparent film.
AB  - This paper describes an ellipsometric method that enables separate measurements
      of refractive index n and thickness d of a transparent film at an arbitrary angle
      of incidence and thus facilitates optical monitoring of a growing film. The
      method is useful for homogeneous transparent films deposited on a transparent
      substrate.

PMID- 20154953
TI  - Measurement of the refractive indices of LiYF(4).

PMID- 20154952
TI  - Brewster angle optical Dewar: construction of an inexpensive model for cryogenic
      or simple liquids for laser Raman scattering experiments.

PMID- 20154954
TI  - Symbols Units Nomemclature: A Omega question.

PMID- 20154955
TI  - Applied optics of optics and opticists.

PMID- 20154956
TI  - Optical activities in industry.

PMID- 20154957
TI  - Patents.
AB  - B 235,925; B 320,603; B 442,280; 3,861,784; 3,861,789; 3,864,030; 3,864,037;
      3,865,490; 3,866,045; 3,868,499; 3,870,399; 3,870,400; 3,870,401; 3,870,402;
      3,871,741; 3,871,748; 3,871,749; 3,871,772; 3,873,189.

PMID- 20154958
TI  - Meeting reports.

PMID- 20154959
TI  - Temporal coherence length and speckle: a simultaneous approach to those problems
      in holography.

PMID- 20154960
TI  - In orbit sun calibration performance of Landsat-2.

PMID- 20154961
TI  - Low charge-voltage frost recording on a photosensitive thermoplastic medium.

PMID- 20154962
TI  - Interpolation of refractive index data: erratum.

PMID- 20154963
TI  - Thickness, uniformity, and preparation of stressfree floating amorphous germanium
      thin-films.

PMID- 20154964
TI  - Carbon dioxide laser absorption coefficients of various air pollutants.

PMID- 20154965
TI  - Observing the sun with a fully tunable Lyot-Ohman filter.
AB  - We describe the properties of the Zeiss Universal Birefringent Filter and its
      optical and electronic interface with the Sacramento Peak Observatory'' vacuum
      telescope. The instrument permits observations of solar intensities, velocities,
      and/or magnetic fields in rapid succession in any Fraunhofer line in the 410-700
      nm wavelength region with high spectral (0.004-0.013 nm) and high spatial (~1/3
      sec of arc) resolution.

PMID- 20154966
TI  - Astronomical Fourier spectrometer.
AB  - A high resolution near ir Fourier spectrometer with the same general design as
      previously described laboratory instruments has been built for astronomical
      observations at a coude focus. Present spectral range is 0.8-3.5 microm with PbS
      and Ge detectors and maximum path difference 1 m. The servo system can
      accommodate various recording modes: stepping or continuous scan, path difference
      modulation, sky chopping. A real time computer is incorporated into the system,
      which has been set up at the Hale 500-cm telescope on Mount Palomar. Samples of
      the results are given.

PMID- 20154967
TI  - Infrared Fourier spectrometer for laboratory use and for astronomical studies
      from aircraft and ground-based telescopes.
AB  - A portable, versatile, ir Fourier spectrometer is described that provides 0.5 cm(
      1) spectral resolution in the 0.87-5.6-microm region. This spectrometer is
      employed in a varied program of astronomical observations from round-based
      telescopes and from the NASA 91.5-cm airborne ir telescope. A number of spectral
      results are presented to illustrate the performance of this spectrometer in
      astronomical applications.

PMID- 20154968
TI  - Ellipsoid-hyperboloid x-ray imaging instrument for laser-pellet diagnostics.
AB  - Analysis of an x-ray imaging system employing ellipsoid and hyperboloid mirrors
      that are confocal and coaxial indicates that spatial resolution of 1-3 microm can
      be obtained. The useful field of view is hundreds of microns, and the collecting
      solid angle is at least 10(3) times that of a pinhole camera. The instrument has
      application to the diagnostics of laser-pellet interactions.

PMID- 20154969
TI  - Determining absolute thermal expansion of titania-silica glasses: a refined
      ultrasonic method.
AB  - Specific test conditions for determining ultrasonic velocities in titania-silica
      glasses are shown to improve the experimentally established linear correlation
      between velocity and thermal expansion. Finer surface finish, normalized thermal
      history (annealing), and controlled temperature for the test specimen improve the
      relationship. A statistical analysis shows that 5-35 degrees C average expansion
      coefficients can be accurately predicted from ultrasonic velocities with a
      standard deviation of 1 ppb/ degrees C. Excellent agreement is established
      between the ultrasonic predicted expansion and test results supplied by the
      University of Arizona Optical Sciences Center.

PMID- 20154970
TI  - Photomultiplier window materials under electron irradiation: fluorescence and
      phosphorescence.
AB  - The fluorescence and phosphorescence of photomultiplier window materials under
      electron irradiation have been investigated using a Sr(90)-Y(90) beta emitter as
      the electron source. Spectral emission curves of uv-grade, optical-grade, and
      electron-irradiated samples of MgF(2) and LiF, and of CaF(2), BaF(2), sapphire,
      fused silica, and uv-transmitting glasses were obtained over the 200-650-nm
      spectral range. Fluorescence yields, expressed as the number of counts in a solid
      angle of 2pi sr/MeV of incident electron energy deposited [MeV(-1) (2pi sr)(-1)],
      were determined on these materials utilizing photomultiplier tubes with cesium
      telluride, bialkali, and trialkali (S-20) photocathodes, respectively. Typical
      yields observed with a uv/visible sensitive bialkali cathode range from 10 MeV(
      1) (2pi sr)(-1) for uv-grade MgF(2) to approximately 200 MeV(-1) (2pi sr)(-1) for
      CaF(2). For comparison, sodium-activated cesium iodide, one of the most efficient
      scintillator materials, yields about 700 MeV(-1) (2pi sr)(-1). High-purity fused
      silica has the lowest yield, approximately 6 MeVW(-1) (2pi sr)(-1). Optical-grade
      MgF(2)and LiF, as well as electron-irradiated uv-grade samples of these two
      materials, show enhanced fluorescence due to color-center formation and
      associated emission bands in the blue and red wavelength regions. Large
      variations in fluorescence intensities were found in uv-grade sapphire samples of
      different origins, particularly in the red end of the spectrum, presumably due to
      various amounts of chromium-ion content. Phosphorescence decay with time is best
      described by a sum of exponential terms, with time constants ranging from a few
      minutes to several days. Phosphorescence intensity expressed as a fraction of the
      steady-state fluorescence intensity is an extremely sensitive measure of
      crystalline perfection and purity. This fraction ranges from a high of
      approximately 10(-2) for some fluoride samples to a low of </=2 x 10(-6) for
      fused silica. Application of the parameters obtained in this work to the analysis
      of recent flight observations on low light-level experiments yields good
      quantitative agreement with flight data from OAO-3, OSO-7, and Apollo 17.

PMID- 20154971
TI  - Temperature dependence and cross sections of some Stokes and anti-Stokes Raman
      lines in ice lh.
AB  - Radiation at lambda = 488.0 nm was used to obtain Raman scattering in ice Ih
      (atmospheric pressure, hexagonal structure). New Stokes spectra were detected for
      frequency shifts less than 50 cm(-1), and new anti-Stokes spectra were observed
      for frequency shifts to -212.5 cm(-1). Measurements of total differential Raman
      scattering cross sections were made for some bands in ice Ih and liquid water.
      The temperature dependence of the ratio of a pair of Stokes-anti-Stokes lines is
      given for ice lh.

PMID- 20154972
TI  - Vacuum ultraviolet radiometry with hydrogen arcs. 2: The high power arc as an
      absolute standard of spectral radiance from 124 nm to 360 nm.
AB  - A wall-stabilized hydrogen arc can be utilized as a standard source of spectral
      radiance since the continuumemission coefficient is calculable to within a few
      percent. Previous efforts to apply this concept have been impeded by relatively
      large uncertainties associated with the plasma diagnostics. The present approach
      yields absolute intensities independent of other radiometric standards or the
      accuracy of any plasma diagnostics. The hydrogen arc is operated at high
      temperatures where the continuum emission coefficient reaches a broad, unique,
      and calculable maximum. Comparisons with other primary standards are consistent
      with the estimated uncertainty in the arc continuum intensities.

PMID- 20154973
TI  - Diffusion constant measurements of macromolecules in solutions containing
      particulate components.
AB  - The analysis and measurement of the dynamic properties of a monodispersed
      macromolecule in a solution containing a distribution of particulate contaminants
      are reported. The resulting measured diffusion constants have values that agree
      with the accepted values found by ultracentrifuge methods. The inclusion in the
      analysis of a simple approximation of the effects of the contaminant background
      eliminates the necessity of ultrapure samples, which are often impractical or
      impossible to prepare.

PMID- 20154974
TI  - Spectroradiometric calibration techniques in the far ultraviolet: a stable
      emission source for the Lyman bands of molecular hydrogen.
AB  - The problems associated with making accurate spectroradiometric measurements in
      the far uv region are sketched briefly. The equipment and methods that were
      developed for providing absolute sensitivity calibration of an Apollo 17 far uv
      spectrometer are described. The absolute reference standards were photoelectric
      diodes calibrated at the National Bureau of Standards. A complete vacuum optical
      facility, which included a premonochromator and stable uv light sources, was
      developed to calibrate the Apollo 17 instrument, and it has been used for a
      number of other tasks. Absolute radiometric calibrations between about 1200 A and
      1700 A were performed with an absolute accuracy of +/-10%. The light source,
      which was designed to provide a very stable light output, is a low-pressure
      molecular hydrogen lamp in which the pressure is stabilized by thermal control of
      uranium hydride powder. Individual emission lines of the Lyman molecular band
      system of H(2) are used for calibration purposes. The lamp also copiously emits
      the 1215.7-A line (Lyalpha) of atomic hydrogen.

PMID- 20154975
TI  - Circular dichroism of poly-D-glutamic acid adsorbed on air-water interfaces.
AB  - A quartz cuvette was modified for use to determine the circular dichroism of
      molecules in thin films at airwater interfaces. By an application of the cuvette,
      circular dichroism spectra of poly-D-glutamic acid at air-water interfaces have
      been compared with circular dichroism spectra of the sample in aqueous solution.
      The results show that poly-D-glutamic acid is a beta structure on the surface of
      the solution in which the alpha helix or random coil is stable.

PMID- 20154976
TI  - Water vapor absorption spectra of the upper atmosphere (45-185 cm(-1)).
AB  - The far ir nighttime absorption spectrum of the earth's atmosphere above 14 km is
      determined from observations of the bright moon. The spectra were obtained using
      a Michelson interferometer attached to a 30-cm telescope aboard a high-altitude
      jet aircraft. Comparison with a single-layer model atmosphere implies a vertical
      column of 3.4 +/- 0.4 mum of percipitable water on 30 August 1971 and 2.4 +/- 0.3
      mum of precipitable water on 6 January 1972.

PMID- 20154977
TI  - Point Visibility Meter: a forward scatter instrument for the measurement of
      aerosol extinction coefficient.
AB  - A new instrument for the measurement of atmospheric extinction coefficient-the
      Point Visibility Meter (PVM)-is introduced and its principle of operation
      discussed. The instrument measures the amount of light scattered at a particular
      forward scattering angle by haze or fog; the extinction coefficient sigma is then
      found from the empirical law relating sigma to the scatter at this angle.
      Detailed calculations of aerosol scattering properties using Mie theory are given
      to support this empirical law. Error estimates based on these calculations
      indicate rms errors of less than +/-12% for a range of sigma values 2-60 km(-1).
      Field trials of the instrument against standard transmissometers confirm these
      theoretical findings and show a linearity of instrumental output with extinction
      coefficient, with an rms error of +/-11.7%.

PMID- 20154978
TI  - Lidar polarization studies of the troposphere.
AB  - The polarization properties of lidar backscattering from the atmosphere have been
      measured using a ruby system operating at 694.3 nm and 347.2 nm. Linearly
      polarized signals are transmitted, and multiple receiver channels simultaneously
      sample the return with polarizers oriented parallel and perpendicular to the
      transmitted polarization. It is found that the polarization of the scattered
      signal varies substantially with meteorological conditions and that the signals
      can be employed to derive useful information about the atmospheric conditions.

PMID- 20154979
TI  - Far-field impulse response verification of selected high-frequency optics
      backscattering analogs.
AB  - Impulse response approximations are presented for selected refractive indices to
      illustrate the variety of pulse returns for dielectric spheres. High frequency
      analogs for the rear axial and glory rays are verified by comparison with
      isolated returns in appropriate impulse responses.

PMID- 20154980
TI  - Diffraction analysis of Doppler signal characteristics for a cross-beam laser
      Doppler velocimeter.
AB  - Based on scalar diffraction theory, single particle scattering characteristics
      for a cross-beam laser Doppler velocimeter (LDV) have been computed for different
      particle sizes under varied instrumentation configurations. The modulating
      component of the scattered signal has been shown to depend upon particle size,
      shape, and collecting aperture for a given probe volume fringe spacing.
      Experimental verifications of some of the predictions are presented, and some of
      the limitations using an LDV as a particle sizing instrument are discussed.

PMID- 20154981
TI  - Optical Fourier analysis of acoustic fields.
AB  - Optical Fourier analysis of acoustic fields is used for the interpretation of
      acoustic disturbances. The method is applied to the study of modes propagating in
      an elastic waveguide. In particular, the mode dispersion curves are determined
      with an accuracy greater than that with purely acoustic methods.

PMID- 20154982
TI  - Excitation of an optical fiber by a Gaussian beam.
AB  - In this paper we present the results of an in-depth analysis of the problem of
      Gaussian beam excitation of optical fibers at normal incidence. The method
      entails the application of the continuity conditions at the interface located at
      the fiber end using Gaussian beams with different spot sizes as our excitation
      source. Next, the simultaneous set of equations obtained is numerically solved
      for the reflected, guided, and radiated modal coefficients and their
      corresponding powers.

PMID- 20154983
TI  - Variable refractive index and birefringent waveguides by sputtering tantalum in
      O(2)-N(2) mixtures.
AB  - Optical waveguides with losses <1 dB/cm at 632.8 nm have been prepared by
      sputtering tantalum in O(2)-N(2) mixtures. As the fraction of N(2) in the
      sputtering atmosphere increases, the refractive index of the guides exhibit a
      sharp maximum and then decreases to a much lower value, and the films become
      birefringent. Using an oxygen discharge, the indices at 632.8 nm for both TE and
      TM modes are 2.083 +/- 0.003, but the values are 1.850 and 1.877, respectively,
      for the highest fraction of nitrogen used. The indices have been measured at
      wavelengths down to 457.9 nm. For low fractions of N(2), the results are
      consistent with a decreasing film density and a constant molecular
      polarizability, but a number of effects, including the birefringence, are
      inconsistent with this picture. Waveguide structures, such as interconnects,
      branching waveguides, and layered directional couplers, have been demonstrated
      using films with different indices. The birefringence has also been verified by
      observation of interference between TE and TM modes simultaneously coupled into
      the guide.

PMID- 20154984
TI  - Distributed-feedback coupling in Ga(1-x)Al(x)As double-heterostructure lasers:
      effect of aluminum concentration.
AB  - The variation of the feedback coupling coefficient in Ga(1-x)Al(x)As distributed
      feedback (DFB) lasers as a function of the Al concentration surrounding the GaAs
      optical confinement waveguide is considered. An optimum thickness for which the
      feedback coupling is maximum is determined for each transverse mode. The largest
      such maximum occurs for the lowest order mode. Fractional Al concentrations that
      yield symmetrical optical waveguides are found to be most effective in minimizing
      threshold current density, with the maximum Al concentrations being limited by
      doping and lattice mismatch considerations.

PMID- 20154985
TI  - Attenuation of giant laser pulses by absorbing filters.
AB  - Three types of absorbing filters were tested for suitability as reproducible
      attenuators for a Q-switched ruby laser beam. None of the filters tested were
      irreversibly damaged when irradiated with pulses having peak powers up to 40 MW
      (beam cross section ~10(-4) M(2)). However, Tiffen Photar neutral density filters
      and Corning filters showed reversible photobleaching (optical saturation) at
      large pulse energies, while Kodak Wratten neutral density filters did not
      saturate.

PMID- 20154986
TI  - Bandlimiting effects in an optical Laplace transform computer.
AB  - Data processing in coherent optical systems has been limited to a large extent by
      operations involving spectrum manipulations through the Fourier transform. By
      appropriate modification of the Green function kernel of the Rayleigh-Sommerfeld
      diffraction integral, it should be possible to obtain transform relationships
      between the input and output of a coherent processor, other than the Fourier
      transform. Cutrona has suggested a possible implementation for a Laplace
      transformer but has apparently not attempted a physical realization [IRE Trans.
      Inf. Theory IT-6, 386 (1960)]. In this study, a Laplace transform computer is
      described in which it is found that spatial bandlimiting is a restriction on its
      usefulness. To compensate for this bandlimiting, a convergence filter is
      described along with a method to produce this and other spatial filters
      physically for optical processors.

PMID- 20154987
TI  - Image restoration by singular value decomposition.
AB  - We demonstrate by a computer simulation example that singular value decomposition
      is a powerful tool for restoring noisy linearly degraded images. We also discuss
      a way of reducing the computation time requirement.

PMID- 20154988
TI  - Optical data storage using PPM and PWM.
AB  - A method for analyzing the binary signal produced by pulse position modulation
      (PPM) and pulse width modulation (PWM) is presented. The results are used to
      study the conversion of analog signals into binary waveforms. The Fourier
      transform is a complex analog signal. A method of using a combination of PPM and
      PWM to make binary Fourier transform holograms of digital data is presented. Two
      optical methods for reading out the optically recorded PPM signals are discussed.
      Experimental results demonstrate the different aspects of these modulation
      techniques for optical storage.

PMID- 20154989
TI  - Laser initiated spark development in an air gap.
AB  - Spark development is studied by 20-nsec image converter photography. A diffuse
      and transparent prechannel bridges the gap from the top of the metal vapor jet,
      which has counterelectrode potential. The prechannel cuts off the development of
      the cone shaped jet with increasing gap voltage. The final breakdown is initiated
      by a z-axis, laser induced filament, which expands into the prechannel volume
      within less, similar10 nsec. This interval represents the final high current
      thermalization phase of the breakdown. Thermal expansion of the initial spark
      channel (Braginskii) follows.

PMID- 20154990
TI  - Measurements of NH(3) absorption coefficients with a C(13)O(2)(16) laser.
AB  - Measurements of NH(3) absorption coefficients are presented for several
      transitions of a C(13)O(2)(16) laser for small concentrations of NH(3) (p </= 1
      Torr) for absorption lines broadened to 1 atm with N(2). NH(3) absorption
      coefficients were determined for laser transitions R(8) (920.2194 cm(-1)) to
      R(28) (933.8808 cm(-1)) of the 00 degrees 1 - [10 degrees 0,02 degrees 0](I)
      band. The strongest absorption coefficient [K = 36.09 +/- 1.43 (atm-cm)(-1)] was
      measured for the R(18) transition for the NH(3) line, aQ(6,6), and is larger than
      has been found in any previous measurements with a CO(2) laser. The dependence of
      K on total pressure was also obtained for select transitions, and the frequency
      separation between the R(18) laser transition and the neighboring NH(3) line
      [aQ(6,6)] was determined to be 550 +/- 50 MHz. These results are significant for
      long path absorption monitoring of NH(3) with CO(2) lasers since the path length
      can be reduced by approximately 40% and for heterodyne mdetection of NH(3) since
      the relative position of the laser transition to the NH(3) absorption line is
      well within the bandpass of Hg-Cd-Te photomixers (B >/= 1.5 GHz).

PMID- 20154991
TI  - Thermal pulse damage thresholds in cadmium telluride.
AB  - A model is presented for predicting the temperature rise in an opaque material
      during the absorption of a moderately short pulse of energy. Experimental
      verification of the model employing a pulsed ruby laser and a cadmium telluride
      plate is described. Two distinct damage thresholds were noted: (1) at modest
      energy levels plastic deformation occurred, and (2) the higher energies resulted
      in surface melting.

PMID- 20154992
TI  - Density perturbations in transonic sluing laser beams.
AB  - A linearized theory is presented for density perturbations induced in a sluing
      laser beam as a function of time after beam turn-on and cross-flow Mach number M.
      The net local density perturbation is expressed as the sum of an isobaric and
      isentropic perturbation. A closed-form solution is obtained for M = 1, where the
      isentropic perturbations peak, and uniform heat addition in a circular beam. The
      results are compared with a corresponding one-dimensional beam. Poor agreement is
      found at large time, where the isentropic density perturbation varies as t and
      t((1/2)) for the one-dimensional and two-dimensional cases, respectively. An
      order-of-magnitude estimate for the final steady-state density perturbation, at M
      = 1, and the time scale in which it is achieved are obtained by consideration of
      nonlinear effects.

PMID- 20154993
TI  - Quasi-stationary population inversion on Kalpha transitions.
AB  - In a search for an x-ray laser capable of operating in a quasi-cw mode, a
      suggested Kalpha-innershell scheme is examined using recently calculated rates.
      This scheme involves the decay of a K-shell vacancy followed by a more rapid (for
      certain elements) L-vacancy decay, which maintains the inversion. The present
      analysis indicates that the scheme is only marginally feasible unless a depletion
      of resonant absorbers is accomplished through line shifts associated with
      multiple ionization following K-vacancy production. The pumping requirements for
      overcoming photoionization losses in the beam and the associated gain conditions
      are estimated for three elements, namely silicon, calcium, and copper, and it is
      concluded that photoionization pumping in a selective energy band is required,
      with emission approaching the blackbody level. A multiline heavy-ion plasma
      source is suggested.

PMID- 20154994
TI  - Interferometry using subnanosecond pulses from TEA nitrogen lasers.
AB  - The applicability of TEA nitrogen lasers emitting at 3371 A for high speed
      optical plasma interferometry of short lived plasmas is demonstrated.
      Interferograms of the dense phase of a 30-kJ plasma focus are obtained with an
      exposure time of less than 500 psec.

PMID- 20154995
TI  - Reconstruction errors in computer generated binary holograms: a comparative
      study.
AB  - The image degradation encountered in reconstructing computer-generated binary
      holograms is compared for the Lohmann-Paris, Lee, and Burckhardt-type hologram
      plots. The results reported here assist one in properly choosing the hologram
      plotting parameters and predicting resulting image quality for each type of
      hologram plot. The analytic results are supported by simulation.

PMID- 20154996
TI  - Homogeneous deformations: determination by fringe vectors in hologram
      interferometry.
AB  - When an object undergoes a combination of minute rigid-body motion and
      homogeneous deformation, its vectorial displacements can be described by a
      general, 3 x 3 matrix transformation. This same matrix can be used to transform
      the sensitivity vector of hologram interferometry into a fringe vector that
      defines the fringes as laminae that are intersected by the surface of the object.
      When fringes are observable on more than one surface of a three-dimensional
      object whose shape is known, it is possible to determine the fringe vector from
      the shape and spacing of the fringes on the object. If three holographic views
      are available, from which three fringe vectors can be determined for three known
      sensitivity vectors, it is possible to determine the transformation matrix, and
      this, in turn, can be decomposed into deformation and rotation matrices. More
      than three views allow the use of least-square-error theory to minimize errors in
      data taking.

PMID- 20154997
TI  - Holographic characteristics of 10E75 plates for single-and multiple-exposure
      holograms.
AB  - The holographic characteristics of Agfa-Gevaert Scientia 10E75 have been examined
      for multiple exposures. They include not only diffraction efficiency, but SNR and
      resolution as functions of number of exposures, time of development, and/or input
      modulation (rho'). The maximum diffraction efficiency, occurring at a density of
      0.7, was observed to increase with increasing development time and decrease as
      the number of exposures increased. An approximately 10% decrease in maximum
      diffraction efficiency was observed for each successive reconstructed image of a
      multiple exposure hologram. Reconstructed noise was found to be fairly well
      represented by grain-noise considerations only for the region 0.1 < rho' < 0.4.
      Elsewhere noise is considerably different from grain-noise predictions. The SNR,
      at a density of 0.7, was observed to increase from 50 to 85 as the number of
      exposures increased from one to four. For postexposure or preexposure holograms
      the maximum signal-to-noise and resolution peaked near an input moduation of 0.4.

PMID- 20154998
TI  - Grating modulated phase plates for holographic storage.
AB  - For holographic data storage a phase mask, which distributes the light evenly
      within the minimum recording area, plays an important role. A new type of phase
      plate making use of grating modulation is proposed and analyzed in this paper
      with some experimental results. Several advantages of the proposed method over
      the conventional phase mask are (1) the capability of direct data input by
      amplitude control of a grating forming each data spot, (2) easy and precise
      control of a phase for each data spot, and (3) independence of wavelength used in
      the recording process.

PMID- 20154999
TI  - Uniform polishing of convex aspheres with an elastic lap.
AB  - An unconventional approach to the uniform polishing of convex glass aspheres is
      described that uses an elastic lapping tool. It is assumed that the asphere has
      been previously ground to the correct shape and that it is desired to remove the
      grind marks by uniform polishing. Uniform polishing is achieved by balancing
      pressure and relative lapping speed effects between the lap and optic. The theory
      necessary to predict optimal polishing machine settings is presented.
      Experimental data are given demonstrating uniform sphere polishing to one wave
      using predicted machine settings without operator intervention.

PMID- 20155000
TI  - Holographic interferometer to test optical surfaces.
AB  - A new interferometric method for testing optical surfaces is given. It is related
      to Murty's Fresnel zone plate interferometer and suggests the fruitful
      applications of holography to this branch of optics. In this paper a theoretical
      model that explains both interferometers is developed. Experimental results and
      pertinent comments are included.

PMID- 20155001
TI  - Standard of flatness: its application to Fabry-Perot interferometers.
AB  - This article briefly describes the first attempts to make liquid and solid
      standard flats. The plane surface of 100-mm diameter polished on a cylindrical
      block of CER-VIT does not show any difference greater than lambda/270 with
      respect to a perfect plane over a circle of 70-mm diameter. After one year of use
      no deformation has been observed.

PMID- 20155002
TI  - Wavefront-error evaluation by mathematical analysis of experimental Foucault-test
      data.
AB  - The diffraction theory of the Foucault test provides an integral formula
      expressing the complex amplitude and irradiance distribution in the Foucault
      pattern of a test mirror (lens) as a function of wavefront error. Recent
      literature presents methods of inverting this formula to express wavefront error
      in terms of irradiance in the Foucault pattern. The present paper describes a
      study in which the inversion formulation as applied to photometric Foucault-test
      measurements on a nearly diffraction-limited mirror to determinewavefront errors
      for direct comparison with ones determined from scatter-plate interferometer
      measurements. The results affirm the practicability of the Foucault test for
      quantitative wavefront analysis of very small errors, and they reveal the fallacy
      of the prevalent belief that the test is limited to qualitative use only.
      Implications of the results with regard to optical testing and the potential use
      of the Foucault test for wavefront analysis in orbital space telescopes are
      discussed.

PMID- 20155003
TI  - Extraordinary-ray and -wave tracing in uniaxial crystals.
AB  - Solutions for tracing the extraordinary ray through a uniaxial nonabsorbing
      birefringent crystal are presented in a simple and explicit form that is directly
      amenable for computer programming. The general case in which the incident ray,
      the optic axis, and the exit surface have arbitrary orientation with respect to
      the entrance surface is treated. Solutions for the extraordinary wave vector
      within the crystal are also given.

PMID- 20155004
TI  - Compound Schmidt telescope designs with nonzero Petzval curvatures.
AB  - A variety of aplanatic and anastigmatic Schmidt Cassegrain and Schmidt Gregorian
      telescope designs with nonzero Petzval curvatures are investigated. Relaxing the
      Petzval constraint permits the development of high performance photo/visual
      instruments which are capable of diffraction limited imaging over fields of view
      of 1-2 degrees .

PMID- 20155005
TI  - Mach-Zehnder data reduction method for refractively inhomogeneous test objects:
      author's reply to comments.

PMID- 20155006
TI  - The parabolic axicon: comments.

PMID- 20155007
TI  - Sagnac or Michelson-Sagnac interferometer?

PMID- 20155008
TI  - Applied optics of optics and opticists.

PMID- 20155010
TI  - Nomenclature of an image forming system.

PMID- 20155009
TI  - Holographic diffraction gratings used in normal incidence monochromators for
      synchrotron radiation.

PMID- 20155011
TI  - Transmittance: an index to shape changes of blood platelets.

PMID- 20155012
TI  - Velocity measurements of blood flow in the capillary and vein using a laser
      Doppler microscope.

PMID- 20155014
TI  - Indiffused waveguides: effects of thin film overlays.

PMID- 20155013
TI  - Indium tin oxide-coated silicon as a selective absorber.

PMID- 20155015
TI  - Propagation of a Gaussian pulse through an optical fiber: applicability of
      geometrical optics.

PMID- 20155016
TI  - Measuring Faraday rotation: a high precision method.

PMID- 20155018
TI  - The parabolic axicon: author's reply to comments.

PMID- 20155017
TI  - Floating optical mount.

PMID- 20155019
TI  - Mach-Zehnder data reduction method for refractively inhomogeneous test objects:
      comments.

PMID- 20155021
TI  - Liquid crystal wedge compensator for display thickness measurement.

PMID- 20155020
TI  - Direct matched-filtering of pen recordings using sodium light.

PMID- 20155022
TI  - Symmetric optimization of dielectric interference filters for nonnormal
      incidence.

PMID- 20155023
TI  - Multiple imaging by a sampling spatial filter.

PMID- 20155024
TI  - Speckle correlation measurement of the velocity of a small rotating rough object.

PMID- 20155025
TI  - Divergence of high order Gaussian modes.

PMID- 20155026
TI  - Graphical aid to the transformation of a laser beam by a thin lens.

PMID- 20155027
TI  - Optics in Switzerland.
AB  - Present work in optics in Switzerland is surveyed, covering universities,
      research institutes, and industry; the review is introduced by a brief historical
      section. The survey was sponsored by the Swiss Society for Optics.

PMID- 20155028
TI  - Deep sea optical viewing systems: methodologies for their analyses and synthesis.
AB  - Methodology is presented for the analysis and synthesis of three model deep sea
      submersible-mounted optical viewing systems. The radiation field of the
      illuminator is characterized by a phenomenological beam model. Several useful
      concepts are introduced: exposure field, exposure contrast field, irradiance
      field, signal-to-noise field, and blur. Certain key exposures and irradiances are
      calculated. Emphasis is placed on the specification of optimum angular field of
      view, optimum height off-bottom, and speed of the submersible as a function of
      the various optical system parameters.

PMID- 20155029
TI  - Computer synthesized filament images from reflectors and through lens elements
      for lamp design and evaluation.
AB  - A mathematical model of the cylindrical, helical filament used in automotive
      forward and signal lighting can be easily written in computer language. By ray
      tracing the filament through reflections off surfaces, accurate pinhole images
      can be synthesized on a computer screen. The buildup of images from this basic
      program can simulate light patterns from reflector-plus-lens headlamps and signal
      lamps, as well as aid in the design of faceted-reflector lamps in which all the
      pattern controlling optics are in the reflector.

PMID- 20155030
TI  - Dynamic Hartmann test.
AB  - The dynamic Hartmann test was developed to monitor precisely the alignment and
      optical figure of a complete telescope system such as the Large Space Telescope
      by using a real star source. The test was chosen for its large range of
      operation, sensitivity, and relative simplicity. The dynamic Hartmann test
      configuration is discussed and analyzed, and the construction of an experimental
      test instrument is described. A wavefront error simulator is used to determine
      experimentally the capability of the Hartmann test instrument in detecting low
      order aberrations under laboratory conditions. It is found that sensitivities in
      the lambda/50 to lambda/100 range can be realized.

PMID- 20155031
TI  - Mode coupling in a multimode optical fiber with microbends.
AB  - Experimental observations of the radiation pattern of a short multimode fiber
      with different induced deformations are reported here. Theoretical calculations
      are also made, based on the assumption of strong coupling between two particular
      modes of the fiber, and are in good agreement with experiment. We obtain
      numerical evaluations of the coupling coefficients and excess loss as a function
      of the amplitude of the deformation, and indications on the requirements to be
      met in cabling the fibers are derived from the experimental results.

PMID- 20155032
TI  - Polarization optics of index-gradient optical waveguide fibers.
AB  - An investigation of the polarization optical properties of index-gradient glass
      fibers confirmed the applicability of the linear birefringent model to fibers of
      this type. The phase retardation (delta(s) = 58 degrees /cm) is homogeneously
      distributed along the whole length of the fiber. The depolarization occurring
      when the incident polarization angle coincides with the fast (or slow) axis of
      the fiber is negligibly small. The measuring technique employed allows the phase
      retardation between the wave components in the privileged directions within the
      fiber to be determined as a function of the temperature (Deltadelta(s)/DeltaT =
      0.09 degrees /K cm). As the fiber is twisted the polarization vector rotates
      synchronously with the twisted endface of the fiber.

PMID- 20155033
TI  - Kramers-Kronig analysis of modulated reflectance data investigation of errors.
AB  - The errors introduced in Deltaepsilon(2) spectra by Kramers-Kronig analysis of
      modulated reflectivity data are investigated using an analytical model. It is
      found that the energy position of singularities is always reproduced with good
      accuracy even if the experimental spectrum of DeltaR/R is cut barely above the
      last structure of interest. This procedure is instead completely insufficient
      when a quantitative line shape analysis is required. In such cases data up to
      very high energy are required for a meaningful analysis. Errors due to other
      sources, like baseline shifts or inaccurate static optical constants, are also
      investigated.

PMID- 20155034
TI  - Mode discrimination with rimmed optical resonator.
AB  - A rimmed optical resonator is studied both theoretically and experimentally. It
      consists of a convex mirror that spreads out the mode volume and an annular
      concave mirror that controls the diffraction loss. It is found that such a system
      is definitely superior to a conventional stable resonator for Fresnel numbers
      larger than unity. It utilizes larger mode volume, yields higher power, and
      discriminates more against higher order modes. However, our system fails to a
      certain extent when it is operated at high power. Methods to remove this
      difficulty are discussed.

PMID- 20155035
TI  - Refractive index profile optimization in diffused graded index lenses.
AB  - Refractive index profiles resulting from simple diffusion processes in glass are
      calculated, and optimum choices of diffusion parameters are chosen from minimum
      error in approximating focusing refractive index profiles. Time dependent
      boundary conditions are shown to result in considerably improved profiles.

PMID- 20155036
TI  - Stress-optic coefficients of ZnSe.
AB  - The stress-optic coefficients of ZnSe have been measured at room temperature;
      Twyman-Green and Fizeau interferometers were used in conjunction with a four
      point loading device. Test specimens were rectangular parallelepipeds of
      chemically vapor-deposited material prepared by Raytheon Corporation.
      Measurements were made with the optical propagation parallel to the deposition
      direction, and optical scanning and computer analysis were employed to determine
      fringe positions to an accuracy of better than 0.01 of a fringe spacing. The
      experimental values for pi(11) and pi(12) are -1.48 +/- 0.05 x 10(-12) m(2)/N and
      +0.22 +/- 0.05 x 10(-12) m(2)/N, respectively.

PMID- 20155037
TI  - Electric field induced second harmonic generation in glass.
AB  - The electric field induced second harmonic coefficient has been measured in
      glass. We have concluded that the nuclear contribution is significantly smaller
      than the electronic contribution, and that this third order effect in glass
      cannot be neglected when measuring the molecular hyperpolarizabilities of most
      organic liquids.

PMID- 20155039
TI  - Contour map display using computer-generated holograms.
AB  - A method for displaying contour maps of two-dimensional functions is described.
      The function is first recorded in a computer-generated hologram (CGH). Then the
      moire formed between the CGH and a regular grating creates a contour map of the
      function. This method allows the number of contours in the moire to be increased
      even after the CGH is made. An example illustrates some interesting results when
      this method is used to display the equipotential lines or the lines of force of
      an electrical dipole in a uniform electric field.

PMID- 20155038
TI  - Representations of space-variant optical systems using volume holograms.
AB  - A technique is described for recording representations of space-variant optical
      systems as volume holograms. The transfer-function holographic representations
      obtained are then placed in the Fourier plane of a coherent optical processor for
      playback. Due to the space-variant nature of the systems represented, the input
      plane of the system to be represented holographically is spatially sampled. As a
      result, the volume hologram medium actually contains a number of holograms that
      have been angle multiplexed to avoid interference problems. Limitations
      associated with the thickness of the recording medium are calculated for imaging
      systems, and experimental results are presented for one lens and two lens
      magnifiers.

PMID- 20155040
TI  - Holographic storage in U-doped LiNbO(3).
AB  - A single LiNbO(3) crystal doped with U ions is a new sensitive phase holographic
      material with high diffraction efficiency and with long thermal decay time of a
      hologram. The energy density of a 4880-A beam from an Ar-ion laser required to
      reach 40% diffraction efficiency is about 1 J/cm(2) for a 1.2-mm thick crystal.
      Diffraction efficiency of a hologram stored in an U-doped LiNbO(3) crystal was
      scarcely reduced from its initial value when the crystal was held at room
      temperature for 150 days.

PMID- 20155041
TI  - Volume holograms in photochromic materials.
AB  - Theoretical expressions are derived describing the process of writing volume (or
      thick) hologram gratings in photochromic materials. The theory includes the
      effects of the saturation of the material response, scattering of the writing
      beams by the partially written hologram, and the refractive index changes that
      accompany the photoinduced absorption changes. Results of representative
      numerical calculations are presented and interpreted in terms of simpler models
      and approximations. Use of the results is illustrated by the calculation of the
      holographic characteristics of an actual material. The results are also related
      to model photochromic systems to estimate the range of achievable holographic
      characteristics and to obtain an approximate procedure to estimate the absorption
      spectra of materials that would give specified holographic characteristics.

PMID- 20155042
TI  - Reflection effects in interferometry.
AB  - Spurious distortions of interference fringes are often encountered in the
      interferometry of planar solidfluid phase boundaries. These distortions mimic
      refractive-index variations near the interface and introduce uncertainty in
      locating the position of the interface on the interferogram. Light reflection
      from the slightly rounded edge of the solid surface has been identified as the
      principal cause of these distortions.

PMID- 20155043
TI  - Far-infrared thin-film beam splitters: calculated properties.
AB  - Properties of beam splitters for a far ir Michelson interferometer have been
      calculated for four plastic materials: Surlyn, Aclar, Mylar, and Kapton. Although
      the materials are birefringent, the averaged optical constants are used; and it
      is shown that this procedure yields valid beam splitter characteristics.

PMID- 20155044
TI  - Aberration generator.
AB  - A new instrument, the aberration generator, has been developed for introducing
      precise amounts of aberration into an optical wavefront. Piston error, wavefront
      tilt, defocus, spherical aberration, coma, and astigmatism can be generated
      either individually or in combination. The instrument can be used to study the
      effects of aberrations on image quality and the optical transfer function for a
      wide variety of optical systems.

PMID- 20155045
TI  - Noncontact optical profilometer.
AB  - The optical profilometer is a measuring instrument that utilizes a laser beam
      reflected from a surface to generate a profile of the reflecting surface. The
      device has been configured in such a manner as to allow stabilization of the
      measured profile with respect to laser intensity fluctuations and the
      reflectivity of the tested object. Measurements can be made quickly and without
      damaging the surface.

PMID- 20155046
TI  - Fourier representation of the energy distribution of an electromagnetic field
      scattered by spherical particles.
AB  - A solution to the scattering problem for spherical particles is presented in
      terms of a Fourier series expansion for the electromagnetic field as well as for
      the corresponding energy distribution. The basic assumptions are the same as for
      the Mie solution. The Fourier coefficients of the energy distribution show a
      systematic behavior as functions of the size parameter alpha = 2piR/lambda (R =
      radius of particle, lambda = wavelength of scattered light), and they depend
      significantly on the complex index of refraction N = n - in k of the particles (n
      = real index of refraction, k = absorption index). These coefficients are
      approximately proportional to the volume of the sphere superimposed with an
      oscillation of Bessel function type with argument (n - 1) alpha. They can be
      measured directly without any intricate Fourier analysis; and since they depend
      in a distinct way on the quantities n and k, they can be used to determine these
      optical properties of particles of an unknown material. The scattering influence
      of a gaseous carr er medium can be eliminated without any experimental
      arrangement just by using an appropriate Fourier coefficient of the scattered
      energy distribution.

PMID- 20155047
TI  - Near-field impulse response examination of backscattering from dielectric
      spheres.
AB  - The backscattered component of the normalized Poynting vector impulse response is
      evaluated at selected times on a plane normal to the direction of pulse
      propagation and in the near field of a dielectric sphere. The computations for
      spheres with refractive indices of 1.60 + 0.01i and 2.25 + 0.01i are consistent
      with the physical interpretations of the high frequency analogs of axial,
      stationary, and glory rays and internal surface waves. Flux maxima associated
      with glory and stationary rays appear first on the axis normal to the plane of
      polarization and change to the axis of polarization as their analogs change
      polarity. Latter stages of the glory ray appear to propagate in a mode similar to
      internal surface waves.

PMID- 20155048
TI  - Thermal recovery processes in laser irradiated HgCdTe (PC) detectors.
AB  - An experimental method for measuring the transient and steady-state thermal
      characteristics of ir photoconductors is introduced. Thermal recovery processes
      in laser irradiated HgCdTe (PC) detectors were investigated. The characteristics
      of thermal recovery processes are found to be quite sensitive to the specific
      details of detector construction. For the most part thermal recovery in these
      detectors takes place on two separate time scales. Initially the signal recovers
      partially to an intermediate level on a time scale of several milliseconds. The
      rest of the recovery occurs much more slowly, i.e., on the order of hundreds of
      milliseconds. It was found that the magnitude of the thermally induced signal,
      the relative importance of the two recovery processes, and the exact shape of the
      thermal recovery curve vary with power density and irradiation time. A one
      dimensional thermal model of the detector for both pulsed and cw laser
      irradiation is presented. Calculated thermal recovery curves are found to agree
      we l with the experimental results for irradiation times as long as 20 msec. The
      two recovery times are found to be due to the two thermally resistive bonding
      layers. The utility of this model for predicting the thermal characteristics of
      new improved detector designs is discussed.

PMID- 20155049
TI  - Optical-mechanical line-scan imaging process: its information capacity and
      efficiency.
AB  - An expression for the information capacity of the optical-mechanical line-scan
      imaging process is derived, which includes the effects of blurring of spatial
      detail, photosensor noise, aliasing, and quantization. Both the information
      capacity for a fixed data density and the information efficiency (i.e., the ratio
      of information capacity to data density) exhibit a distinct single maximum when
      displayed as a function of sampling rate, and the location of this maximum is
      determined by the system frequency response shape, SNR, and quantization
      interval.

PMID- 20155050
TI  - Spectrometers working on the same extensive continuum source: an estimation of
      the relative performances of eight instruments.
AB  - The SNR's predicted for three types of Hadamard transform spectrometer, a
      Michelson Fourier spectrometer, SISAM, PEPSIOS, and grating monochromators and a
      grating spectrograph all observing an extensive continuum source are estimated
      and compared in both photon and receiver noise limited conditions. This
      complements a previous paper [J. Meaburn, Appl. Opt. 12, 279 (1973)] dealing with
      spectrometers for extended line emission sources in a similar way.

PMID- 20155051
TI  - Total reduction of distorted echelle spectrograms: an automatic procedure.
AB  - We describe a semiautomatic procedure for the reduction of high-dispersion
      echelle spectra recorded with an image tube. The spectra are traced with a
      computer-controlled microdensitometer that scans along the curved spectral
      orders. The curvature of each order is calculated approximately by a FORTRAN
      program from known grating and distortion parameters. A typical spectrum includes
      25 orders (covering 1500 A) and is traced with a slit 0.012 A wide. To produce an
      atlas of intensity vs wavelength and to determine the equivalent widths of 300
      lines currently require a day. We discuss the reduction procedures and time
      requirements in detail.

PMID- 20155052
TI  - Practical multi-spectrum Hadamard transform spectrometer.
AB  - We have constructed a Hadamard transform spectrometer (HTS) which simultaneously
      obtains fifteen ir spectra, each having 255 spectral elements. Spectra are
      obtained essentially in real time through use of a minicomputer with 8K words of
      memory and a CRT display. This permits operation of the instrument in the field.

PMID- 20155053
TI  - Diffraction limitations for plasma electron density measurements with schlieren
      methods.
AB  - Restrictions imposed by diffraction on schlieren electron density measurements
      are discussed. Applicability criteria are derived. It is shown that diffraction
      partly compensates for the advantage of longer wavelengths: while the deflection
      angles increase with lambda(2), the gain in measuring precision increases only
      with radicallambda. The criteria are not restricted to a particular spectral
      range. However, they were derived with special regard to extending schlieren
      methods to the far infrared (FIR).

PMID- 20155054
TI  - Plasma flow and fast particles in a hypervelocity accelerator: a color
      presentation.
AB  - A new concept for particle acceleration for micrometeoroid simulation was
      developed at NASA Marshall Space Flight Center, using a high-density self
      luminescent fast plasma flow to accelerate glass beads (with a diameter up to 1.0
      mm) to velocities between 15-20 km/sec. After a short introduction to the
      operation of the hypervelocity range, the eight-converter-camera unit used for
      the photographs of the plasma flow and the accelerated particles is described.
      These photographs are obtained with an eight-segment reflecting pyramidal beam
      splitter. Wratten filters were mounted between the beam splitter and the
      converter tubes of the cameras. The photographs, which were recorded on black and
      white film, were used to make the matrices for the dye-color process, which
      produced the prints shown.

PMID- 20155055
TI  - Patents.
AB  - 3,847,484; 3,847,485; 3,850,504; 3,851,169; 3,851,949; 3,853,405; 3,856,402;

PMID- 20155056
TI  - Circular polarization in certain laser and holography applications: comments.

PMID- 20155057
TI  - Multiple-exposure holography: addendum.

PMID- 20155058
TI  - Of optics and opticists.

PMID- 20155059
TI  - Crosstalk reduction in optical switching.

PMID- 20155060
TI  - Thermal blooming vs linear absorption in a vertical beam.

PMID- 20155061
TI  - Fourier spectrum of an object using holographic lenses.

PMID- 20155062
TI  - Speckle-shearing interferometry: a simple optical system.

PMID- 20155063
TI  - Differential spectrophone measurements of the absorption of laser energy by
      atmospheric dust.

PMID- 20155064
TI  - Mechanical modification to the EU-700 monochromator.

PMID- 20155066
TI  - Circular polarization in certain laser and holography applications: author's
      reply to comments.

PMID- 20155065
TI  - Evaluation of r(omicron) for propagation down through the atmosphere: correction.

PMID- 20155067
TI  - Data distribution using fiber optics.
AB  - This paper reviews some considerations that need to be addressed in applying
      fiber optic transmission lines to the distribution of data to a number of remote
      terminals. Considerations are given to system components such as sources,
      receivers, and connectors as well as distribution formats.

PMID- 20155068
TI  - Modal dispersion in multimode graded-index fibers.
AB  - A complete analysis of the propagation characteristics of a ray through an
      axially symmetric graded-index medium is carried out in the geometrical optics
      approximation. First, two constants of the motion are shown to exist for a ray
      propagating in an infinite medium. Secondly, these constants of the motion are
      shown to be invariant when reflection occurs on the core-cladding interface of
      cladded graded index fibers. This conservation law allows the study of the
      propagation characteristics of a ray through a fiber even though its trajectory
      may be discontinuous because of reflection at the core-cladding interface. The
      temporal behavior of various cladded parabolic-index fibers is given by their
      impulse responses when excited uniformly by parallel beams under different input
      angles. Rays are shown to propagate in two different ways: a reflected type of
      propagation takes place through reflections on the core-cladding interface, and a
      selfocusing type of propagation where rays go through the fiber core without
      touching the cladding.

PMID- 20155069
TI  - Spectral transmission characteristics and chromatic dispersion of uv optical
      fibers.
AB  - Schott's uv fiber optics with special organic cladding are supposed to increase
      the spectral transmission response at lower wavelengths. However, it was observed
      that chromatic dispersion occurred when certain geometrical arrangements of the
      fiber were made. Spectral transmission characteristics were analyzed in detail
      for both coherent and incoherent radiation sources. The cause of this chromatic
      dispersion is presently unknown.

PMID- 20155070
TI  - Bending losses of dielectric slab optical waveguide with double or multiple
      claddings: theory.
AB  - Bending-loss formulas of a multilayer planar optical waveguide are obtained on
      the basis of continuation of wave functions without solving the complicated
      eigenvalue equation. We then consider the bending losses of a doubly clad slab
      waveguide in which the core has the largest refractive index, and the inner
      cladding has the lowest. Bending losses are shown to be drastically reduced by
      inserting low-index inner claddings between the core and the outer cladding.

PMID- 20155071
TI  - Backscattering patterns of step index optical fibers: angular width.
AB  - Angular widths of laser backscattering patterns from optical fibers with thin
      claddings due to rays reflected by core-cladding interface are investigated.
      Calculated and measured values are presented and found to be in good agreement. A
      summary of different backscattering patterns from clad fibers is given.

PMID- 20155072
TI  - Real-time optical correlation.
AB  - A real-time coherent optical correlator is described that uses the Itek PROM as a
      recyclable filter recording medium. Operation of a joint transform correlator is
      compared to a conventional Vander Lugt system. Experimental results are shown for
      the joint transform system, including demonstrations of the effects of target
      alignment and scale and the correlation of random bit rasters for signal
      processing applications.

PMID- 20155073
TI  - Polycube optical memory: a 6.5 x 10(7) bit read-write and random access optical
      store.
AB  - A random access optical memory for write-read-write operation is proposed. The
      memory is designed on the basis of a nonvolatile magnetooptic photoconductor
      sandwich storage material (MOPS) that offers high optical sensitivity. The
      optical addressing part of the memory consists of an He-Ne laser, digital light
      deflection combined with passive beam splitting and simple optics. The addressing
      is organized in blocks of about 10(3) bits. First experimental results measured
      at a system model being developed in our laboratory are presented, as well as
      results of storage experiments at a magnetooptic photoconductor sandwich.

PMID- 20155074
TI  - Propagation of spatial pulses in interferometrically produced guiding structures.
AB  - Image transfer properties of interferometrically produced dielectric light guides
      are investigated. A general technique of analysis is developed. Computer
      calculations based on this approach are used to study the behavior of pulses
      traversing the guiding structures for various values of refractive index.
      Experimental results are obtained using photosensitized polymethyl methacrylate
      as the recording material. Computer results are compared with existing theory and
      found to be in close agreement.

PMID- 20155075
TI  - Use of an ac heterodyne lateral shear interferometer with real-time wavefront
      correction systems.
AB  - An analysis is performed to determine the accuracy with which an ac heterodyne
      lateral shear interferometer can measure wavefront aberrations if a white light
      extended source is used with the interferometer, and shot noise is the
      predominate noise source. The analysis shows that for uniform circular or square
      sources larger than a derived minimum size, the wavefront measurement accuracy
      depends only upon the radiance of the source and not upon the angular subtense of
      the source. For a 1-msec integration time, a 25-cm(2) collecting area, and a
      source radiance of 10 W/m(2)-sr the rms wavefront error is approximately 1/30
      wave, assuming the signal is shot noise limited. It is shown that for both
      uniform circular and square sources an optimum shear distance is approximately
      (1/2) the aperture diameter required to resolve the light source. Comments are
      made on the optimum shear for nonuniform radiance distributions.

PMID- 20155076
TI  - Multilayer GaAs-Al(0.3)Ga(0.7)As dielectric quarter wave stacks grown by
      molecular beam epitaxy.
AB  - Single crystal quarter wave multilayer stacks consisting of alternating layers of
      GaAs and Al(0.3)Ga(0.7)As were grown on GaAs substrates by the molecular beam
      epitaxy method. This technique is capable of a very high degree of control of
      film thickness and layer reproducibility. The measured reflectivity spectrum is
      in good agreement with the reflectivity dispersion of GaAs and Alo.gGao.7As.
      calculated from the equivalent layer theory using the known index dispersion of
      GaAs and GaAs and Al(0.3)Ga(0.7)As.

PMID- 20155077
TI  - Moisture resistant optical films: their production and characterization.
AB  - We have used an accelerated humidity test consisting of a 24-h cycle between 27
      50 degrees C at 95% relative humidity to rate the moisture resistance of typical
      protective films such as CaF(2), LaF(3), and fluorinated polymers (TFE, FEP)
      deposited on BaF(2) and NaCl substrates. The test life of BaF(2) specimens was
      increased from about 4 cycles to over 9, 26, and 42 cycles when protected by
      CaF(2), TFE, and LaF(3), respectively. Heat treating the as-deposited CaF(2)
      films further improved specimen life by a factor of 2. The lifetime of NaCl
      specimens was improved from a fraction of a cycle to 1 and 3 cycles,
      respectively, by CaF(2) and TFE coatings. No adherent LaF(3) films could be
      deposited on the salt. Microhardness measurements of the CaF(2) films showed a
      direct correlation with humidity resistance. The effect of heat treatment was
      apparently to sinter the fine CaF(2) particles composing the film, thus
      increasing film density, refractive index,and hardness while reducing moisture
      permeability. Caf(2) and TFE films function as antireflective, as well as
      protective layers, on BaF(2) and NaCl.

PMID- 20155078
TI  - Reflectance and durability of Ag mirrors coated with thin layers of Al(2)O(3)
      plus reactively deposited silicon oxide.
AB  - A technique for producing adherent and well-protected front surface Ag mirrors
      with an evaporated Al(2)O(3) + SiO(x) overcoat and an evaporated Al(2)O(3)
      underlayer is described. A thin Al(2)O(3) layer promotes adhesion between the Ag
      film and its substrate. The optimum thickness of each outer layer necessary to
      give good adhesion and protection to the Ag surface with minimal loss in
      reflectance due to ir absorption was found to be about 300 A for the Al(2)O(3)
      layer and between 1000 A and 2000 A for the SiO(x) film. Ag surfaces coated in
      this fashion retained a normal incidence reflectance in excess of 95% over the
      wavelength region from 450 nm to the far ir, even when exposed to harsh sulfide
      and humidity environments. Calculations demonstrate the advantage of using
      protected front surface Ag in comparison to more durable metal reflectors, such
      as Al or Rh, in terms of high reflectance and low visible region polarization.
      However, a very pronouncedrestrahlen reflectance and absorption effect in the
      thicker SiO(x) film is responsible for a calculated drop in reflectance from
      98.5% to about 65% at lambda = 8.1 mum and 45 degrees incidence for the Ag +
      Al(2)O(3) + SiO(x) coating.

PMID- 20155079
TI  - Spectral enhancement of near uv xenon flashlamps.
AB  - The addition of certain elements to xenon flashlamps can result in a factor of 2
      3 enhancement of the emitted energy in the 2500-3000-A spectral range. The degree
      of enhancement is dependent on the dopant and discharge current.

PMID- 20155080
TI  - Gain saturation in distributed feedback lasers.
AB  - An approximate method is presented for the analysis of overcoupled distributed
      feedback lasers. A closed form expression is obtained for the power emitted by a
      laser normalized to the saturation power in terms of the loss coefficient
      alpha(L), small signal gain coefficient alpha(0), coupling parameter kappa, and
      length of the laser L. The result is compared with published computer solutions,
      and good agreement is obtained in the range |kappa|> 4; qualitative agreement
      extends to |kappa|L = 1. The closed form expression is adapted to predict the
      saturation behavior of leaky-wave lasers.

PMID- 20155081
TI  - Mode properties of annular gain lasers.
AB  - The properties of a new class of laser resonators are investigated theoretically
      and experimentally. In these lasers the radiation propagates longitudinally in an
      annular amplifying medium, and useful low loss modes can be obtained even when
      the axial region is obscured. Alignment characteristics and far field patterns
      are discussed, and experiments have been conducted using coaxial double-discharge
      CO(2) devices.

PMID- 20155082
TI  - Fundamental absorption edge in laser window CdTe.
AB  - Fundamental absorption edge and the ir absorption at 10.6-microm wavelengths have
      been studied in CdTe laser window samples of varying optical quality. The results
      show that the edge spectroscopy can be used as a sensitive diagnostic technique
      for evaluating the over-all optical quality of the material.

PMID- 20155083
TI  - Angular properties of blackbody simulators.
AB  - Aperture-cavity wall radiative exchange is described for various extended
      blackbody simulator cavities by means of a simple proper angular parameter in
      terms of the angle of observation.

PMID- 20155084
TI  - Performance testing of electrostatically focused uv-visible image converters with
      deflection capability.
AB  - Two prototype uv to visible image converter tubes with image deflection
      capability, produced by the En- glish Electric Valve Company, Ltd., have been
      tested with respect to performance parameters related to the photometric and
      imaging properties of the tubes. The two converters were electrostatically
      focused with a triode structure and were magnetically deflectable. The tests were
      executed at a facility for abso- lute intensity calibrations in the visible and
      vacuum uv spectral region available at the Max-Planck-Institut fur
      Extraterrestrische Physik. Test procedures and results are reported.

PMID- 20155085
TI  - Errors in Hadamard spectroscopy or imaging caused by imperfect masks.
AB  - An analysis is given of the errors in Hadamard spectroscopy that are caused by
      transparent slits in the mask being systematically wider or narrower than they
      should be. It is shown that if the input spectrum consists of a single line, the
      distorted spectrum that is actually calculated consists of this line, plus four
      small blips. When the transparent slits are too wide, these blips are of equal
      height and the same sign, one pair surrounding the line, and another pair
      displaced a certain distance from it. When the slits are too narrow, the
      displaced blips have the same amplitude, but are negative. The response to an
      arbitrary input spectrum is then determined from this. The same method of
      analysis may also be used to handle other types of errors.

PMID- 20155086
TI  - Simple derivative optical spectrometer.
AB  - A wavelength modulation spectrometer that can be easily assembled is illustrated.
      The apparatus, which employs a double beam scheme with two detectors followed by
      standard electronics, allows the simultaneous detection of absorption (or
      reflection) spectra and their logarithmic derivatives. The smallest modulation
      that can be detected has been found to be ~10(-5) A(-1) when the bandpass is ~2
      A.

PMID- 20155087
TI  - Two-point fluorophotometer for the human ocular fundus.
AB  - A new technique for making on-line recordings of fluorescein dilution curves from
      two locations in the human retina has been devised. A modified Zeiss fundus
      camera with two optical fibers mounted in a scanning ocular collects the light
      emitted by fluorescein dye from two spots in the fundus. Two fiber-optic cables
      transmit the collected light to a photomultiplier. The detector output current is
      transmitted to a two-channel pulse sorter. The output signals from the pulse
      sorter are amplified and displayed on a two-channel recorder. Since this
      technique utilizes only small amounts of fluorescein, multiple measurements in
      the same subject are possible.

PMID- 20155088
TI  - International comparison of measurements of luminance factor and reflectance of
      white diffusing samples.
AB  - During the 1966-1971 period, an international comparison was made of measurements
      of the luminance factor and reflectance of pressed tablets of MgO and BaSO(4) and
      of MS-14 opal glasses. Twelve laboratories from eleven countries took part, many
      of them national standardizing laboratories. Variations in the manufacture of the
      pressed tablets and the effect of cleaning the opal glasses limited the precision
      of the comparison to some extent, but some useful information emerged. The
      interlaboratory variation was +/-0.3% for the pressed tablets and +/-0.6% for the
      opal glasses. Samples with improved properties should be developed for future
      intercomparisons of this type.

PMID- 20155089
TI  - Remote detection of pollutants using resonance Raman scattering.
AB  - Calculations of the resonance Raman cross section for several diatomic molecules
      are presented. These results are used, together with recent measurements of large
      resonance enhancements in NO(2) and SO(2), to estimate the sensitivity of a lidar
      system based upon the resonance Raman effect.

PMID- 20155090
TI  - Furnace temperature profiles: measurement by spectroscopic methods.
AB  - The determination of atmospheric temperature profiles from ir radiance data
      transmitted by satellites is fast becoming a reliable meteorological tool.
      However, high temperature applications of the technique have hitherto been
      restricted, the main difficulty being poor convergence beyond temperature peaks.
      This paper shows that by modifying an existing atmospheric iterative inversion
      technique to combine radiance measurements from two detectors at each end of a
      common line of sight through the hot gas, retrieval of the temperature profile is
      possible over the whole gas slab. Practical applications include research into
      burner and rocket design and tighter control of industrial furnace operation.

PMID- 20155091
TI  - Electromagnetic field components: their measurement using linear electrooptic and
      magnetooptic effects.
AB  - Vector components of alternating electric and magnetic fields can be measured
      with excellent sensitivity and time resolution using a laser system employing
      Pockels effect or Faraday effect materials as field sensors. This technique
      offers the advantages of being passive and remote; the sensor material requires
      no power source and can be interrogated by a remotely located laser transmitter
      and receiver with no connecting wires or electrodes. This paper analyzes the
      sensitivity of the electrooptic and magnetooptic methods and derives new figures
      of merit for materials used as sensors in these applications. Experiments
      evaluating the temperature coefficients of sensitivity and demonstrating that
      sensitivities of 0.06 V/cm and 0.5 G can be achieved easily are described.

PMID- 20155092
TI  - Low-noise extended-frequency response with cooled silicon photodiodes.
AB  - With appropriate preamplifier design and cooled silicon photodiode and input
      field effect transistor, broad frequency bandwidth (e.g., 0.01 Hz to 100 kHz)
      performance comparable or better than that of photon noise limited
      photomultipliers can be achieved. The FET input preamplifier is operated current
      mode with a large feedback resistance. Consequent limited frequency response of
      the preamplifier is compensated by treble boosting at the postamplifier. Cooling
      the photodiode and input FET to 200 K eliminates photodiode dark current and FET
      gate reverse current shot noises as significant contributors. Remaining noise
      sources are FET voltage noise, minimized by small input capacitances, and
      feedback and FET load resistances Johnson noise. At an output SNR of 10, for
      example, the internal noise and the photon noise are about the same level. Thus
      the performance gain attributable to the photodiode's high quantum efficiency can
      be significant.

PMID- 20155093
TI  - Short wire as a microwave analogue to molecular Raman scatterers.
AB  - The frequency changes in the spectra of microwave radiation reflected from
      rotating or vibrating short wires are strongly reminiscent of optical Raman
      spectra from rotating or vibrating molecules. The analogy is examined and found
      to be quite good for rotation, although less so for vibration. The effect of
      rotation of the wire is an amplitude modulation, whereas that of vibration is a
      pulse modulation. The relation betwen the change in freauencv and the Doppler
      effect is also examined, since the rotational effect may be considered as a
      classical, first-order, ond-order Doppler effect. transverse Doppler shift
      completely unrelated to the relativistic second-order Doppler effect.

PMID- 20155094
TI  - Intensity fluctuations of optical radiation in scattering media.
AB  - The results of theoretical and experimental investigations of intensity
      fluctuations of optical radiation in model media (suspensions of a great number
      of macroscopic particles) and in a turbid atmosphere are given. The theoretical
      calculation is made in two approximations: (1) the particles are on the average
      in a wave zone of each other; (2) large soft particles are in the near zone of
      one another. In both approximations all the intensity statistical characteristics
      including multipoint probability distributions are obtained. The results of the
      experimental investigation of intensity fluctuations in model media and a
      comparison of those with the theoretical ones are listed. For a turbid atmosphere
      the results of the experimental investigation of intensity fluctuations are
      given.

PMID- 20155095
TI  - Transient thermal blooming of single and multiple short laser pulses.
AB  - Energy transfer through absorbing media with pulses short compared to the
      acoustic transit time has been investigated experimentally and theoretically for
      collimated beams in a homogeneous wind field. Two experimental approaches were
      used: a low intensity cw CO(2) laser probe beam technique giving a continuous
      record of the lensing of the medium following the transmission of a coaxial high
      power TEA laser pulse and a direct determination of high power pulse train
      blooming using a thermofax covered drum. The experimental results support the
      predictions of a geometric optics perturbation solution as well as those of
      existing propagation codes. An interesting case, namely, enhancement resulting in
      a 20-30% increase of the original nonbloomed peak intensity is observed when the
      pulse separation time is approximately 1-2 times the wind flow time across the
      beam.

PMID- 20155096
TI  - Instantaneous intensity distribution in a focused laser beam at 0.63 microm and
      10.6microm propagating through the atmosphere.
AB  - Experimental results from investigations of instantaneous intensity distributions
      in focused laser beams at 0.63 microm and 10.6 microm at a distance of
      approximately 5 km are presented and discussed. At 0.63 microm the beam pattern
      is broken into several diffraction-scale spots because focusing is saturated. At
      10.6 microm the beam pattern is almost uniform. This is valid for beam dimensions
      smaller than the correlation length of the amplitude.

PMID- 20155097
TI  - Tracking systems requirements for atmospheric steering compensation.
AB  - The effects of transmitted laser beam steering due to atmospheric turbulence can
      be corrected by the use of a tracking sensor that views the receiver through the
      same turbulence. For an airborne transmitting system, the power spectrum of the
      steering can have high frequency components. The tradeoff between the aperture
      size for the tracking sensor, the laser transmitting aperture size, and the
      bandwidth of the closed loop tracking system are shown.

PMID- 20155098
TI  - Wavefront error simulator for evaluating optical testing instrumentation.
AB  - A wavefront error simulator has been designed and fabricated to evaluate
      experimentally test instrumentation for the Large Space Telescope (LST) program.
      The principal operating part of the simulator is an ab- erration generator that
      introduces low-order aberrations of several waves magnitude with an incremented
      adjustment capability of lambda/100. Each aberration type can be introduced
      independently with any desired spatial orientation.

PMID- 20155099
TI  - Focus screen optimization.
AB  - Ground glass used for camera focus screens often has far from optimum diffusion
      properties. An analysis of the function of the focus screen shows that a screen
      with random (Gaussian) diffusion properties can be constructed with both
      brightness and focus efficiencies above 84%. These considerations have led to the
      design of an unusually bright and effective focus screen for the Polaroid SX-70
      Land camera.

PMID- 20155100
TI  - Polarization of light sources: a photographic method.
AB  - The degree of polarization and the inhomogeneity of the light emitted by light
      sources are assessed by means of a photographic method. Some results are
      presented for Nernst glowers and deuterium discharge lamps.

PMID- 20155101
TI  - Thin films: a survey as of April 1975.
AB  - This report appeared in the ICO Bulletin for June 1975, an intermittent
      publication of the International Commission for Optics. O. S. Heavens is the ICO
      rapporteur for thin films. A report by A. Vasko on the ICO-10 Congress held in
      Prague in August 1975 will appear in an early 1976 issue of Applied Optics.

PMID- 20155103
TI  - Applied optics of optics and opticists.

PMID- 20155102
TI  - Optical activities in industry.

PMID- 20155105
TI  - Complex-waist Gaussian beams and unstable resonators.

PMID- 20155106
TI  - Beryllium mirrors: 10.6-microm characterization.

PMID- 20155107
TI  - Frequency stabilization of internal mirror He-Ne lasers in a transverse magnetic
      field.

PMID- 20155108
TI  - Measurement of the microm sized radius of Gaussian laser beam using the scanning
      knife-edge.

PMID- 20155109
TI  - Apodized aperture using frustrated total reflection.

PMID- 20155110
TI  - Erbium laser as a remote sensor of methane.

PMID- 20155111
TI  - Absorption coefficient of atmospheric dust and other strongly absorbing powders:
      an improvement on the method of measurement.

PMID- 20155112
TI  - Coupling efficiency between GaAIAs laser and low loss optical fibers.

PMID- 20155113
TI  - Preparation of silica glass using a CO(2) laser.

PMID- 20155114
TI  - Hologram gratings: amplitude and phase components.

PMID- 20155115
TI  - Photocounting distributions with variable dead time.

PMID- 20155116
TI  - Instant spectroscopy in the visible, ultraviolet, and vacuum ultraviolet with
      Polaroid film.

PMID- 20155117
TI  - Quantum efficiency of a channel electron multiplier in the far ultraviolet.

PMID- 20155118
TI  - Rayleigh centennial.
AB  - This brief sketch of the contributions of the fourth Baron Rayleigh is intended
      to supplement the biographical material contained in the October 1964 issue of
      Applied Optics.

PMID- 20155119
TI  - Sky color near the horizon during a total solar eclipse.
AB  - A theory for the color of the sky near the horizon for an observer in the umbral
      region of a total solar eclipse is presented. The model uses a Rayleigh
      scattering atmosphere, and the light reaching the observer is a beam of singly
      scattered sunlight, which, in turn, has suffered depletion by scattering in its
      passage from outside the shadow region. The model predicts both the red color
      observed in the lowest 8 degrees of the sky for the total solar eclipse of 30
      June 1973 and the enriched blue color of the sky at any elevation angle greater
      than the solar elevation angle. The model is also adapted to explain the
      reddening of the horizon sky observed during such times as when a dark cloud
      passes overhead or when the light from a large city is seen from the distance at
      night.

PMID- 20155120
TI  - Sky brightness during eclipses: a review.
AB  - This paper is abstracted from the introductory section of "Sky Brightness During
      Eclipses: A Compendium from the Literature," AFCRL-TR-74-0363, Special Reports
      180, Air Force Cambridge Research Laboratories, Hanscom AFB, Massachusetts 01731.
      This report should be consulted for fuller details and tables.

PMID- 20155121
TI  - Optical wind sensing by observing the scintillations of a random scene.
AB  - We demonstrate the feasibility of using a naturally illuminated scene, such as a
      hillside or forest, as a passive optical source to measure the path-averaged
      crosswind between the scene and the observer. The resultant path weighting
      function for the crosswind cannot be varied arbitrarily, but we can obtain a
      useful range of weighting functions by adjusting the geometry of the receiver.

PMID- 20155122
TI  - Mass absorption indices of various types of natural aerosol particles in the
      infrared.
AB  - The mass absorption index of aerosol particles has been measured in the 2-17
      microm wavelength region. The measurements were performed on films of aerosol
      particles that were collected by an automatic jet impactor at polluted and
      various uncontaminated remote sites. All but marine aerosols possess strong
      absorption bands in the transparent part of the atmospheric long-wave spectrum,
      indicating marked influence of aerosol particles on the radiation budget of the
      atmosphere.

PMID- 20155123
TI  - Phase-front distortion of laser radiation in a turbulent atmosphere.
AB  - The phase-front distortion of laser radiation propagating through the turbulent
      atmosphere has been measured simultaneously at several wavelengths in the visible
      using a long-range Mach-Zehnder interferometer with high spatial and temporal
      resolution (476 nm </= lambda </= 647 nm, 0.5 mm </= Deltar 60 mm Deltat = 0.5
      msec, z </= 2 km, C(n) = 1.3 x 10(-7) M(-1/3)). Phase-structure function,
      transverse coherence length, and arrival-angle fluctuations are interpreted in
      terms of the meteorological quantities turbulence strength and turbulence
      structure and inner and outer scale. The investigation covers the strong
      turbulence regime (scintillation saturation regime) where wave coherence is
      essentially determined by phase effects. In this regime a breakup of the phase
      front is found to occur.

PMID- 20155124
TI  - Scattering of electromagnetic waves by arbitrarily shaped dielectric bodies.
AB  - The differential scattering characteristics of closed three-dimensional
      dielectric objects are theoretically investigated. The scattering problem is
      solved in a spherical basis by the Extended Boundary Condition Method (EBCM)
      which results in a system of linear equations for the expansion coefficients of
      the scattered field in terms of the incident field coefficients. The equations
      are solved numerically for dielectric spheres, spheroids, and finite cylinders to
      study the dependence of the differential scattering on the size, shape, and index
      of refraction of the scattering object. The method developed here appears to be
      most applicable to objects whose physical size is on the order of the wavelength
      of the incident radiation.

PMID- 20155125
TI  - Cloud-base water content measurement using single wavelength laser-radar data.
AB  - Monochromatic backscattering laser-radar data are used for the determination on
      the number density of cloud droplets within a cumulus cloud base. The method is
      based upon general properties of a cloud base as derived from in situ
      measurements in a large variety of continental cumulus clouds. The backscatter
      laser profile from the cloud base is analyzed, and points with equal optical
      depth values are detected in each profile. The method of detection requires no
      knowledge of the multiple scattering contribution, even though its effect is not
      neglected and is allowed to vary as a function of the optical depth. Corrections
      for general clouds are suggested based upon lidar measurements and analysis of
      the backscattering profile characteristics.

PMID- 20155126
TI  - Horizontal visibility and the measurement of atmospheric optical depth of lidar.
AB  - In this paper we describe a generalized treatment of the atmospheric visibility
      distances for a variety of atmospheric conditions. In the development of the
      formula for the visibility distance, it is shown how a series of assumptions made
      in the early work of Koschmieder [Beitr. Phys. Atmos. 12, 33 (1924)] can be
      reduced to a single assumption covering more atmospheric conditions. Special
      attention is paid to the cases in which the extinction coefficient is wavelength
      dependent. It is shown that neglecting such a dependence may produce errors as
      large as 20-100%, especially when long visibility distances are considered. The
      use of a dye-laser radar for the remote sensing of visibility distances is
      described and discussed.

PMID- 20155127
TI  - Optical contamination evidence from Skylab and Gemini flights.
AB  - Final results from a part of the T027 experiment that was performed on the first
      Skylab mission are presented. The sample array system containing 248 optical
      surfaces and exposed outside the orbital workshop did not collect any significant
      contaminants. Unfortunate performance compromises and the relative cleanliness of
      the assembly on the antisolar side placed the amount of available surface
      contaminants at or below the limiting sensitivity of the ground measuring
      instruments. However, significant contamination was seen near the extravehicular
      hatch quadrant on the solar side of the orbiting assembly, and some results from
      returned samples are presented. Optical windows and mirrors exposed on the Gemini
      12 mission showed degradation up to 35% in the uv wavelength region and solar
      absorptance increases up to 1.8 times the clean values. An expression for the
      attenuation coefficient vs wavelength is presented. The contaminant, a silicone
      base material, varied in thickness from 22 nm to 88 nm. The postflight sca ttered
      luminance of a contaminated Gemini 12 left-hand spacecraft hatch window was used
      to obtain threshold stellar visibility curves as a function of scattered and
      incident sunlight angles.

PMID- 20155128
TI  - Diffuse reflectance of the ocean: some effects of vertical structure.
AB  - Monte Carlo computations of the diffuse reflectance of an ocean consisting of two
      homogeneous layers with differing optical properties are presented, along with a
      simplified method of computation that uses results of previous Monte Carlo
      simulations. It is demonstrated that it is impossible to distinguish between thin
      layers of strong scattering and thick layers of weak scattering through
      measurement of the diffuse reflectance. Analyzing the two-layer reflectance under
      the assumption of a homogeneous ocean yields an optical property that is shown to
      be nearly the average of the associated property over the penetration depth of
      the medium, i.e., the depth over which the downwelling irradiance falls to l/e of
      its value at the surface.

PMID- 20155129
TI  - Gas cell correlation spectrometer: GASPEC.
AB  - A new gas filter correlation spectrometer (GASPEC), for the remote detection of
      trace vapors in the atmosphere by means of natural emission in the ir, is
      described. Unique optical features of the GASPEC include two detectors using a
      single focal plane chopper plus an optical reference for electronic gain
      balancing. Continuous sensor balance and calibration are achieved along with the
      source radiometric and target gas information. Several GASPEC instruments have
      been built and tested including devices to sense CH(4), C(2)H(6), HCI, and CO.
      Some preliminary data taken with these sensors are presented.

PMID- 20155130
TI  - Ion implanted photodiode detectors in epitaxial (Ga(x) In(1-x))As.
AB  - Ion implanted p-n junction photodiodes in epitaxially grown (Ga(x) In(1-x))As
      material are reported on here. Photoresponse in these diodes was investigated for
      approximately the entire composition range of 0 < x < 1. High values for quantum
      efficiency were obtained for the devices with a high value of x. Peak
      D(*)(lambda,f) of greater than 10(11) [cm(Hz)(1/2)/W] at room temperature was
      obtained at 0.8-microm wavelength, while a peak D(*)(lambda,f) of 5 x 10(10)
      [cm(Hz)(1/2)/W] was obtained at 165 K at 1.4-microm wavelength.

PMID- 20155131
TI  - Vortex heat exchanger cooling for ir detectors.
AB  - Recent developments on a no-moving-parts expander device suggest an ir detector
      cooling technique with improved reliability, weight, and cost advantages.

PMID- 20155132
TI  - Optical constants of minerals and rocks.
AB  - Lorentz line parameters (and estimates of their standard deviations) have been
      empirically derived from measured reflectance data for muscovite mica, an
      anorthosite, a diopsidic pyroxenite, an almandite-pyrope garnet, and a soda lime
      glass. These parameters provide a useful starting point for computer calculations
      requiring optical constants as a function of frequency and are therefore given
      here. A novel method of fitting the reflectance data by least squares is
      described in detail, as is the statistical procedure for estimating the standard
      deviations of the parameters found.

PMID- 20155133
TI  - Double beam fluorescence spectrophotometer: design and typical applications.
AB  - A double beam fluorescence spectrophotometer has been designed for the analytical
      control laboratory and for some research applications. It has several modes of
      operation in addition to double beam, in which the difference in fluorescence
      between two samples is measured. The design concept (developed by Ohnishi)
      employs equivalent optical paths for both beams, an optical chopper, and a time
      sharing electrooptical system. Since it is a true double beam system it may also
      be used to record the percent transmission spectrum of a sample, which is placed
      in monochromatic light, as both excitation and emission monochromators are
      scanned synchronously. For identification of pure samples in dilute solutions a
      relative quanta excitation spectrum may also be recorded. Some applications for
      the double beam fluorescence concept are to improve quantitative results by
      eliminating interference due to scatter and due to unwanted fluorescence peaks,
      to control product quality by matching two samples of similar characteristics and
      to assay trace organic compounds.

PMID- 20155134
TI  - Spectral emission signatures of ambient temperature objects.
AB  - This report describes the preliminary work to collect the ir spectral emission
      signatures of ambient temperature objects using a Fourier transform spectrometer
      operating in the 8-13-microm region of the electromagnetic spectrum. Details of
      the construction of a sample container are presented along with a description of
      the spectrometer, the controlling computer, and the data collection techniques
      and procedures. A system test, which is actually the ratio of two blackbodies at
      different temperatures, indicates that these procedures are valid. The
      emissivities of Krylon 1602 ultraflat black paint, crushed fused quartz, and
      three types of cotton are presented.

PMID- 20155135
TI  - Transmittance ratio of a compensator.
AB  - Simplified formulas are given for the calculation of the transmittance ratio of a
      compensator. The measurementscheme based on these formulas has the following
      advantages: (1) the value of transmittance ratio is not influenced by the
      calibration error and imperfections of the polarizer, and (2) a prior exact
      calibrationof the compensator and the analyzer is not required. It is shown that
      the relative calibration errorbetween the compensator and the analyzer can be
      determined from the experimentally measured angles. The error analysis of the
      formulas is presented to provide an understanding to minimize the uncertainty of
      the final results. Finally the scheme has been applied to the calibration of a
      Babinet-Soleil compensator and the results are presented.

PMID- 20155136
TI  - Periodic nonsinusoidal vibration: effects in matched filtering for detection of
      signals buried in noise of uniform spectral density.
AB  - In the present paper, the effects of periodic nonsinusoidal vibrations of spatial
      filters in signal detection experiments are considered. Performance degradation
      of such an optical information processing system is shown graphically, assuming
      that the signal is buried in noise of uniform spectral density. Results are
      compared with those in the presence of pure sinusoidal vibrations of the spatial
      filter. It is observed that the performance of the system decreases with the
      increase in departure from the pure sinusoidal case.

PMID- 20155137
TI  - Wide aperture optical correlator-spectrum analyzer: evaluation of a new design.
AB  - A wide-aperture optical correlator-spectrum analyzer has been developed that
      achieves its full theoretical maximum processing gain of 36 dB. This 4000-channel
      system is coherent across the 100-mm-diam aperture with 100-lines/mm resolution
      at the center. The system noise is not perceptible, and the time-bandwidth
      product is 9000. Performance tests are described and evaluated for aperture
      coherence, Fourier transform accuracy and resolution, and processing gain.

PMID- 20155138
TI  - Beat frequency between two axial modes of a He-Ne laser with internal mirrors and
      its dependence on cavity Q.
AB  - Differences of the beat frequencies of a He-Ne laser in two-frequency operation
      up to 1.8 MHz in the two different states of polarization are observed. These
      differences of the beat frequencies are explained by the dependence of the beat
      frequency on the cavity Q, using Lamb's theory. A method of measuring the cavity
      Q of a passive laser resonator as a function of the direction of polarization of
      the external exciting radiation is described. The linear dependence of the
      difference of the beat frequencies DeltafII,I and DeltafI,II from the difference
      of the reciprocal values of the cavity Q factors 1/Q(II) and 1/Q(I), derived from
      Lamb's theory for the simple case of midtuning, is proved qualitatively by
      experiments.

PMID- 20155139
TI  - Effect of cavity transients and rotational relaxation on the performance of
      pulsed HF chemical lasers: a theoretical investigation.
AB  - Two rate-equation models of a pulsed HF laser are presented. Calculations with
      these models reveal the time evolution of the gain and intensity of lasing on all
      lines in vibrational-rotational bands studied and the time histories of
      concentrations of the chemical species. The present formulation permits an
      accurate assessment of the effect of vibrational relaxation and rotational
      relaxation. The model predictions are compared with earlier models to illustrate
      their unique features. Multiline lasing on vibrational-rotational bands is
      predicted; however, the general trends of J shifting are similar to those of
      earlier models. It is found that lasing does not begin when the medium gain
      reaches threshold, but intensity increases sharply after the gain is far above
      threshold. The gain subsequently drops rapidly and oscillates near the threshold
      value. The effect of rotational relaxation on laser performance is shown for
      multiline laser operation, and the enhancing effect of cascading is clearly
      revealed. The present models are found to predict output and performance
      consistent with experiment.

PMID- 20155140
TI  - Display devices in image processing.
AB  - Hardware arrangements and methods are proposed in which optoelectronic devices,
      such as image converters and special purpose CRT's, are used for image processing
      operations, e.g., correlations-integral transforms, such as the Fourier
      transform, filtering, implementation of special algorithms, and one-dimensional
      functional representations. These operations are to be performed in parallel or
      partly in parallel at an over-all speed far exceeding that of a fast digital
      computer, with the output appearing as sequential electric signals. The accuracy
      will be adequate for experimental but not for analytic inputs. Specific
      recommendations are made on needed improvements in the performance of display
      devices and the standardization of developmental models, which would permit
      optimization of the proposed systems and increase their range of applicability.

PMID- 20155141
TI  - Photoinduced polarization properties of LilO(3) single crystal.
AB  - Photoinduced polarization is achieved in a lithium iodate single crystal by the
      simultaneous application of a dc field and illumination from a uv source. The
      dark depolarization and photodepolarization current decay characteristics of the
      polarized samples have been studied in detail in this paper.

PMID- 20155142
TI  - Thin grating couplers for integrated optics: an experimental and theoretical
      study.
AB  - A detailed account is given of the practical and theoretical aspects of grating
      or periodic couplers. Such couplers are used to launch light into thin film
      optical waveguides. The theoretical description stresses considerations of
      reciprocity. A Green's function formulation is used to calculate the radiated
      fields occurring when a guided wave is incident upon a grating coupler.
      Experiments were performed on grating couplers, formed in photoresist on top of
      thin film waveguides of 7059 glass deposited on glass of lower refractive index.
      Measurements of the coupling length and proportion of power in the various beams
      are presented as a function of the grating period for waveguides supporting one
      and many modes. Good agreement is found between the theoretical and experimental
      results. The methods used in the fabrication of the gratings are discussed in
      detail, and guidelines for the design of grating couplers are given.

PMID- 20155143
TI  - Kerr cell light modulator with crossed fields.
AB  - A cell with two identical pairs of electrodes oriented at 90 degrees is examined.
      When both elements are submitted to the same dc voltage and to two ac voltages
      having the same amplitude but phase-shifted by 180 degrees , the birefringence of
      the cell is proportional to the ac voltage as in a Pockels cell. Modulation
      experiments on the cell containing deionized nitrobenzene are presented and
      analogies and differences with Pockels cells are emphasized.

PMID- 20155144
TI  - Coupling optical waveguides by tapers.
AB  - The coupling of single-mode optical waveguides through the use of expanding and
      contracting tapers is examined theoretically. In particular, the problems of
      angular and transverse misalignments of an input and output taper are
      investigated along with the effects of the taper itself. A tradeoff is found to
      exist, that is, widening the guide by means of a taper leads to less critical
      coupling tolerances for transverse displacements, but tighter tolerances for
      angular misalignment. Similar considerations apply to large core singlemode
      fibers.

PMID- 20155145
TI  - Reflection losses from imperfectly broken fiber ends.
AB  - This paper presents an approximate theory for determining the reflection losses
      in multimode fibers that terminate in end surfaces that are not strictly
      perpendicular to the fiber axis. This theory is also applicable to tilts and
      covers step index as well as parabolic index fibers. The cross section of the
      step index fiber is assumed to have square geometry. This assumption simplifies
      the theory and is not expected to influ-ence the obtained results.

PMID- 20155146
TI  - Radiation losses of the HE(11) mode of a fiber with sinusoidally perturbed core
      boundary.
AB  - The radiation losses of the HE(11) mode of a fiber with sinusoidal radius
      fluctuations are calculated in the weak guidance approximation. The loss formula
      is derived by means of the volume current method and also by using coupled mode
      theory. The result presented here extends earlier results to the case of
      radiation escaping nearly perpendicular to the fiber axis.

PMID- 20155147
TI  - Multigroove embossed-plastic splice connector for joining groups of optical
      fibers.
AB  - To install and maintain successfully an optical fiber communications system,
      techniques for splicing individual and groups of optical fibers under field
      conditions must be developed. In this paper a technique for splicing groups of
      optical fibers with a one piece multigroove embossed plastic connector is
      described. Using 132-microm multimode fibers with 94-microm core diameters, the
      average transmission loss of the splice joints measured was 0.12 dB with a
      standard deviation of 0.11 dB and a range of loss values from 0.0 dB to 0.53 dB.

PMID- 20155148
TI  - Absorption coefficients in highly transparent solids: barothermal theory for
      cylindrical configurations.
AB  - The development of highly transparent solids requires improved methods to measure
      very low absorption coefficients at laser wavelengths. For the case in which a
      laser beam passes through a weakly absorbing solid that is surrounded by a
      confined, nonabsorbing gas, the temperature profiles in the solid and the
      temperature and pressure profiles in the gas have been calculated. Our
      calculations suggest that sufficient heat transfers from the solid into the gas
      to produce an easily detected pressure rise in the gas.

PMID- 20155149
TI  - Nonlinear absorption in direct-gap semiconductors.
AB  - Nonlinear absorption coefficients have been calculated for certain direct-bandgap
      semiconductors at 0.694-microm, 1.06-microm, 1.318-microm, and 10.6-microm
      wavelengths and compared with experimental results. The second- order
      perturbation theories of Braunstein and Basov yield underestimates and
      overestimates, respectively, of the nonlinear absorption constants. The numerical
      values are dependent upon the use of appropriate effective band masses,
      dielectric constants, and electron spin degeneracy factors. However, the Keldysh
      model gives second-order absorption constants that are intermediate between the
      two perturbation calculations. Although the Keldysh model often underestimates
      the value, in general, it yields the estimate of the magnitude of the two-photon
      absorption coefficient. The one-photon band-edge absorption in GaAs and InSb is
      predicted surprisingly well by the Keldysh model.

PMID- 20155150
TI  - Absorption of thin film materials at 10.6 microm.
AB  - Absorption indices at a wavelength of 10.6 mum for thin films of As(2)S(3), GeSe,
      BaF(2), ZnSe, and CdTe were measured by calorimetric techniques with a CO(2)
      laser. The values obtained, 4.6 x 10(-4), 1.4 x 10(-3), 2.8 x 10(-3), 2.8 x 10(
      3), and 5.0 x 10(-3), respectively, were significantly greater than the
      corresponding values for the bulk materials. This difference was least for the
      vitreous films, As(2)S(3) and GeSe, which also had a lower absorption than the
      remaining polycrystalline films. Details are presented of the microstructure of
      the films as determined by scanning electron microscopy and k-ray diffraction.

PMID- 20155151
TI  - Attenuation measurement in low-loss optical glass by polarized radiation.
AB  - For the production of fiber waveguides suitable for optical communications
      cables, glasses with extremelylow attenuation are required. A new method is
      described for measuring the optical attenuation of bulk glasses in the wavelength
      range of 0.4-1.1 microm. Using a quartz halogen source with highly stabilized
      radiation power, a linearly polarized, monochromatic, collimated beam was
      produced, passing the sample at the Brewster angle. Transmission loss, residual
      reflection, and surface scattering were measured by low-noise photodiodes and
      integrating digital voltmeters. A stability of 10(-5) and a resolution of 10(-5)
      or better were achieved. Results for two different kinds of commercial glasses,
      fused quartz (Ultrasil) and synthetic vitreous silica (Suprasil W1), are reported
      and discussed.

PMID- 20155152
TI  - Optical parameters of partially transmitting thin films. 1: Basic theory of a
      novel method for their determinations.
AB  - In the method described, two coherent light beams are directed at the partially
      transmitting film in such a way that two new beams are emitted. A comparison
      between the intensities of the outgoing beams enables one to determine the
      thickness, refractive index, and absorption coefficient of the film. One
      advantage of the method is that no absolute values of light intensities or
      polarization must be determined. This.part of the work describes the basic theory
      of the new method. Experimental verification of the theory and further analysis
      of the characteristics of the method are left for Part 2.

PMID- 20155153
TI  - Pump-induced optical distortions in disk amplifier modules: holographic and
      interferometric measurements.
AB  - Interferometric measurements have been made of the optical distortions induced in
      laser disk amplifiers during the flashlamp pumping pulse. Both conventional
      interferometric methods and the techniques of double exposure holographic
      interferometry were used to identify four major sources of pump-induced optical
      distortions: subsonic intrusion of hot gas (traced to leakage of atmospheric
      oxygen into the amplifier), microexplosions of dust particles, thermally induced
      optical distortions in the glass disks, and gaseous optical distortion effects
      caused by turbulent flow of the purging nitrogen gas supply used within the laser
      amplifier head. Methods for reducing or eliminating the effects of each of these
      optical distortions are described.

PMID- 20155154
TI  - Minimax spectrum shaping with a bandwidth constraint.
AB  - A new approach to spectrum shaping, in which the maximum of the spectrum is
      minimized subject to a constraint on the bandwidth, is considered. The results
      can be applied to a variety of methods of digital holography. A lower bound for
      the maximum and a figure of merit are obtained. Practical methods for minimax
      shaping of the spectrum are described and compared via computer simulations. The
      results of these simulations indicate that the lower bound is relatively tight,
      and the figure of merit is a good one.

PMID- 20155155
TI  - Properties of (Se,S)-based chalcogenide glass films, and an application to a
      holographic supermicrofiche.
AB  - In a (Se,S)-based chalcogenide glass system, the optical property, such as
      transmission and refractive index, changes reversibly within amorphous phase when
      the sample is heated and light irradiated. The refractive index in the light
      irradiated state is larger than that in the heated state, and the amount of
      change Deltan reaches 0.05 ~ 0.1 in the visible wavelength region. The merits of
      this glass system as a recording material are high resolving power and
      rewritability. As an application, a rewritable holographic supermicrofiche, which
      is partially refreshable, and its experimental system are given. Characteristic
      features of this material as applied to an information retrieval system are
      discussed.

PMID- 20155156
TI  - Projection-type white-light reconstruction of 3-D images from a strip-shaped
      hologram.
AB  - Projection-type unidirectional holography is a promising three-dimensional
      imaging technique. However, the high cost of lasers in the reconstruction
      degrades its usefulness. This paper proposes a white-light-reconstruction version
      of the projection-type holography. The principle, design theory, and experiments
      are described. When a hologram is illuminated by a white light, the diffracted
      light exhibits color dispersion. The proposed method features the use of a
      holographically prepared diffraction grating for the compensation of the
      dispersion and of a simple device (called an optical channel) to cut off the
      nondiffracted components. Photographs of the reconstructed images show good
      agreement with the theory.

PMID- 20155157
TI  - Relative flatness measurement of uncoated optical flats.
AB  - A method is described for measuring the relative flatness of uncoated precision
      optical flats to lambda/1000. The method uses scanning interferometry and can be
      made automatic fairly readily.

PMID- 20155158
TI  - Infrared spectrometer: liquid-helium-cooled rocketborne circular-variable filter.
AB  - An ir spectrometer used to obtain atmospheric emission spectra from a rocket at
      altitudes between 45 km and 200 km in the ICECAP Auroral Measurements Program is
      described. The instrument continuously scans the 6.75-23.2-microm spectral region
      at the rate of 2 scans/sec. The spectral resolution of the instrument, which
      employs a circular-variable interference filter (CVF), ranges from 3% to 4%. The
      entire optical subsection, silicon-arsenic detector, CVF, Irtran 6 lens, baffle,
      and removable cold cover are cooled below 10 K in a high-vacuum Dewar system. The
      noise equivalent spectral radiance (NESR) of the spectrometer at 22 ,microm is
      better than 1 x 10(-11) (W cm(-2)sr(-1)microm(-1)). The dominant high altitude
      atmospheric emission features observed on two rocket flights were 9.6-microm O(3)
      and 15-microm CO(2).

PMID- 20155159
TI  - Multireflection Raman cell: a design.
AB  - The construction and some of the calculations for a new multireflection Raman
      cell are described. The cell has a small volume, may be used at high pressures
      and low temperatures, and is intended for use with a laser and a spectrometer.
      The cell constructed yields a scattered light signal 4 to 5 times that possible
      with an optimum double pass laser illuminated cell. Higher gains can be achieved
      by altering the cell dimensions.

PMID- 20155160
TI  - Monolithic interferometric angle sensor.
AB  - A high-resolution dynamic angle sensor has been constructed in the form of an
      equal-path solid fused silica interferometer. This paper describes the design,
      construction, and experimental evaluation of an anglesensing interferometer that
      can resolve angular changes of 0.1 sec of arc over large rotation angles at
      angular rotation rates of 10 degrees /sec.

PMID- 20155162
TI  - Patents.
AB  - 3,830,558; 3,861,781; 3,861,783; 3,864,018; 3,864,019; 3,874,770; 3,876,290;
      3,876,292; 3,877,783; 3,879,105; 3,883,752; 3,884,555; 3,884,556; 3,884,557;
      3,885,862; 3,887,262; 3,887,263; 3,887,264; 3,887,269; 3,889,282; 3,891,302;
      3,891,304; 3,891,310.

PMID- 20155161
TI  - Eighteenth century optics: the Cartesian-Newtonian conflict.
AB  - The eighteenth century is often regarded as a period when optics was stultified
      by Newton's dominant influence and the controversy of two rival hypotheses: the
      wave theory and the corpuscular theory of light. However, a study of the
      controversial development of achromatic lenses reveals a deeper underlying
      conflict between two different types of mechanistic philosophy-one Newtonian and
      the other Cartesian. This conflict, both methodological and cosmological, pitted
      inductivism against deductivism. Two pivotal issues were the role of mathematics
      and the nature of experimentation. Here we have a clear example of h e
      interaction of science and philosophy.

PMID- 20155163
TI  - Confocal LDV utilizing a decoupling beam splitter combiner.

PMID- 20155165
TI  - Path differencing: an improvement to multipass absorption cell measurements.

PMID- 20155164
TI  - High-power laser refractory metal mirrors made of thoriated tungsten.

PMID- 20155166
TI  - Applied optics of optics and opticists.

PMID- 20155169
TI  - Patents.
AB  - 3,782,806; 3,802,778; 3,803,407; 3,804,521; 3,806,224; 3,807,832; 3,808,422;
      3,811,096; 3,813,544; 3,849,742; 3,851,951; 3,852,683; 3,852,684; 3,855,546;
      3,855,547; 3,856,403; 3,857,109; 3,857,636; 3,860,343; 3,860,884; 3,860,888;
      3,865,975; 3,868,169; 3,871,739; 3,872,400; 3,869,210; 3,872,402; 3,872,403;
      3,872,407; 3,876,829; 3,880,522; 3,880,523; 3,883,688.

PMID- 20155168
TI  - Remote Doppler velocity measurements of atmospheric dust devil vortices.

PMID- 20155170
TI  - Laser fusion target illumination system: comments.

PMID- 20155171
TI  - Mode properties of annular gain lasers: erratum.

PMID- 20155173
TI  - Multi-aperture diffraction.

PMID- 20155172
TI  - Approximation to the incomplete gamma function for strong-line absorptance model.

PMID- 20155174
TI  - Pulse clipping for holographic interferometry.

PMID- 20155175
TI  - Holographic interferometry: identification of circuit board component failure.

PMID- 20155176
TI  - Sand erosion effect on the 10.6-microm optical absorption of coated ZnSe.

PMID- 20155177
TI  - Diamond turning and polishing of infrared optical components.

PMID- 20155178
TI  - Vibrational relaxation rate of HF(2) by HF.

PMID- 20155179
TI  - Twin-prism separator for retinal stereophotography.

PMID- 20155180
TI  - Kitt Peak 60-cm vacuum telescope.
AB  - Described is a major new tool for solar research, conceived and built during a
      time of budget restraint.The observation of magnetic and velocity (circulation)
      field structure on a synoptic basis and with diffractionlimited resolution is the
      aim. New optical features include the use of oversize mirrors and windows(to
      avoid thermal edge effects) and the placement of the coelostat feed outside the
      vacuum, mainly foreconomy. The site selected has prevailing winds that clear
      thermals from these mirrors. Test data in theform of the system MTF and optical
      transmission, together with examples of full disk magnetograms
      andphotoheliograms, show present performance capability. Measured MTF indicates a
      response of 0.2 at 1sec of arc (whereas diffraction-limited response would be
      ~0.8). System transmission, including the accompanying spectrograph, is only 2-3%
      (lambdaO.44-1.1 microm). Thus, both the optical quality and efficiency aresubject
      to improvement.

PMID- 20155181
TI  - Solar magnetograph employing integrated diode arrays.
AB  - A solar magnetograph employing as detectors a pair of self-scanning 512-element
      integrated diode arrays is described. Coupled to a 1.5-m telescope, photospheric
      flux as small as 5(10(16)) maxwells is detected, corresponding in intensity to
      DeltaI/I = 3(10(-4)) at lambda 0.8688 microm. Measured photometric properties of
      the diode array are given, including MTF as a function of wavelength, dark
      current as a function of temperature, completeness of readout, optical and
      electronic fixed-pattern noise. An integrating preamplifier is presented that
      achieves a measured noise, when connected to the array, equivalent to 950
      electrons at the input for a bandwidth of 3(10(5)) Hz. These data provide a basis
      for an evaluation of the detector performance at low light levels beyond the
      needs of the magnetograph. Operated at near liquid nitrogen temperature, the
      noise and cooling characteristics indicate the detector has promise as a low
      light level sensor.

PMID- 20155182
TI  - Heat trap: an optimized far infrared field optics system.
AB  - An ir field optics system has been designed that achieves the maximum flux
      concentration allowed by the Abbe sine inequality and provides efficient coupling
      to bolometer-type detectors.

PMID- 20155183
TI  - Two-chopper technique for measuring fluorescence lifetimes.
AB  - This paper describes a two chopper technique for making fluorescence lifetime
      measurements when the pump source and the fluorescence are at the same
      wavelength. By pumping directly into the emitting state, delays due to relaxation
      from higher lying pump bands are avoided, while at the same time, the technique
      eliminates the problem of detector saturation when pumping directly into the
      fluorescing level.

PMID- 20155184
TI  - Direct current cataphoretic effects on Hg 2537-A radiation from Hg + Ar
      discharges (dc fluorescent lamps).
AB  - The Hg 2537-A intensity from Hg + Ar discharges was measured as an independent
      function of mercury vapor pressure (as influenced by a cold spot temperature) at
      various constant currents and tube radii with ~4-Torr argon. As a function of
      mercury pressure, the intensity rises to a peak (which defines an optimum mercury
      cold spot temperature) and then decreases with further increase in mercury
      pressure due to the combination of self-absorption and electron deexcitation. The
      behavior of the optimum mercury cold spot temperature is dependent upon ac or dc
      conditions. For ac, the optimum mercury pressure is ~7 mTorr (corresponding to a
      Hg cold spot temperature of ~40 degrees C) and comparatively insensitive to
      current. By contrast, the optimum mercury cold spot temperature for the dc case
      is dependent upon whether the anode end or cathode end is cooled. The dc lamp
      with anode end cooled yields an optimum mercury cold spot temperature less than
      40 degrees C and decreases with increasing current, while the optimum with
      cathode cooled is greater than 40 degrees C and increases with increasing
      current. We believe that the peak intensity always occurs at the same real
      mercury density (because that determines the self-absorption), but the Hg cold
      spot temperature required to achieve this density is affected by dc cataphoretic
      pumping phenomena.

PMID- 20155185
TI  - Application of a Fabry-Perot spectrometer to the measurement of spectral line
      shifts much smaller than line width.
AB  - It is shown that the presented method employing a Fabry-Perot spectrometer is
      significantly superior to existing methods using grating instruments of
      comparable size. The optimum choice of instrumental parameters is given. The
      method was employed to measure the flow velocity of an argon plasma jet via the
      Doppler effect of the 4158-A line. Results of these measurements are given.

PMID- 20155186
TI  - Spectral estimation techniques for the spectral calibration of a color image
      scanner.
AB  - Several methods of spectral sensitivity estimation for color image scanners are
      developed and evaluated. The estimation procedure involves response measurements
      of the scanner through a set of spectrally selective filters. These measurements
      form the observations for generalized inverse, smoothing, and Wiener estimation
      processes. Wiener estimation is found to provide the best results.

PMID- 20155187
TI  - Spectral emission of corona discharges.
AB  - Corona-discharge devices are commonly used in a variety of research and
      development applications. They are known to produce a considerable amount of
      electromagnetic radiation, mainly in the uv region of the spectrum. The mechanism
      involved is presumed to be the ionization and radiative recombination of the
      gases surrounding the high-voltage terminal of the device. A series of high
      resolution emission spectra of corona discharge has been measured in atmospheres
      of nitrogen, helium, and air. (The nitrogen and helium are Air Products 99.995%
      purity, total hydrocarbons less than 0.5 ppm.) These data are presented here and
      are compared with published spectroscopic reference data. All the emission lines
      reported in the spectroscopic reference literature were detected, as well as
      other lines, which may conceivably be due to impurities.

PMID- 20155188
TI  - Chopping factors for circular and square apertures.
AB  - For the cases of circular and square apertures, calculations are presented for
      the beam size dependence of the chopping factor that is the factor relating beam
      intensity to that component of the intensity passing a filter tuned to the
      chopping frequency. For small beams, a value of 0.45 applies, but as the beam
      size approaches the chopping blade size, its value decreases and becomes geometry
      dependent. Complete numerical calculations are given for the case of a circular
      chopping wheel, but it is shown that analytic results of an approximation are
      usually sufficient. Harmonics of the chopping factor are also presented.

PMID- 20155189
TI  - Cavity radiators: an ecumenical theory.
AB  - Multiple reflection considerations give cavity emissivity as an infinite series
      of nested integrals. The Liou-ville-Neumann series solution to the Fredholm
      integral equation of the second kind gives the same series for integral equation
      formulation of the cavity problem when the walls are gray, Lambertian, and
      isothermal. A compact solution, derived from the series, stimulates interesting
      comparisons among the multiple reflection analyses of Gouffe, De Vos, Treuenfels,
      Kelly, and Bartell and Wolfe and the integral equation theories of Sparrow,
      Albers, and Eckert; Sparrow and Jonsson; Syndor; Bedford and Ma; and Chandos and
      Chandos.

PMID- 20155190
TI  - Time integrating acoustooptic correlator.
AB  - This paper describes an acoustooptic technique for achieving signal correlation
      with a time-bandwidth product of 10(6)-10(8), using existing devices. One signal
      is used to intensity modulate a light beam that illuminates an acoustic cell. The
      other signal appears in the cell as a traveling wave and is Schlieren imaged onto
      a detector array. The detected image intensity is integrated in time, achieving
      the desired correlation function. Since the correlation integration is performed
      in time rather than space, the time-bandwidth limitations of earlier acoustooptic
      correlators are greatly reduced. Experimental procedures for implementation of
      this technique are discussed and results shown.

PMID- 20155191
TI  - Optical image processing by multiplex coding.
AB  - Multiplex coding of optical images is discussed for photon-counting operation in
      both the signal- and dark-count-dominated domains. Both intensity measurement and
      signal detection are discussed. The advantage of multiplex operation in both
      situations is demonstrated and comparison made with alternative imaging
      techniques. The effects of code noise, detector area, response time, and dynamic
      range are discussed. It is shown that in dark-count-dominated operation, e.g., ir
      imaging applications, the limiting factor on multiplex gain is the light
      collection following image coding. Higher bandwidth detection is also required:
      for instance, a typical ir detector transmitting a 100 x 100 element image with
      individual element resolution of 2(5) will need a total dynamic range of 2(12)
      and an exponential response time a factor of 2.4 faster than for a single
      detector.

PMID- 20155192
TI  - Masks for Hadamard transform optics, and weighing designs.
AB  - This paper gives a brief survey of the design of masks for Hadamard spectrometers
      and image scanners. Three different criteria are described for judging a mask, as
      well as techniques for choosing masks that are not too far from the optimum.

PMID- 20155193
TI  - Effect of surface roughness on change of the polarization state of light
      reflected from silicon and germanium.
AB  - The optical effect of surface roughness on a scale below the wavelength of light
      can be represented as a transitional layer between the bulk substrate and the
      vacuum. Using two different models of that layer, we calculated the changes of
      the ellipsometric parameters. Comparison of the results of this calculation with
      the actual optical behavior of the silicon-germanium substrate is presented.

PMID- 20155194
TI  - Optical parameters of partially transmitting thin films. 2: Experiment and
      further analysis of a novel method for their determination.
AB  - In Part 1 of this work a theory was developed for the measurement of the
      thickness, refractive index, and absorption coefficient of a partially
      transmitting thin film. In the present work, an experimental system is described
      and the basic theory verified by actual measurements. It is shown how the
      measurement of intensity ratios in a single setup is adequate for the
      determination of the above mentioned parameters. In addition, the application of
      the system for the examination of optical surface quality is demonstrated.
      Finally, the theory is extended to nonnormal incidence.

PMID- 20155195
TI  - Power dependence of reflectivity of metallic films.
AB  - The reflectivity of vacuum-deposited gold films on quartz glass substrates was
      studied as a function of 10.6-microm radiation power density. A simple linear
      model of the temperature dependence of the absorptivity of the gold film is
      developed. This temperature dependence is coupled with a three-dimensional heat
      flow analysis and fits the experimental data well. The absorptivity alpha is
      written as alpha(0)(1 + betaT) and the values of alpha(0) and beta are
      determined, respectively, as (0.88 +/- 0.01) x 10(-2) and 12 x 10(-4)/ degrees C.

PMID- 20155196
TI  - Antireflection coating prepared by plasma polymerization of perfluorobutene-2.
AB  - Plasma-polymerized coatings of perfluorobutene-2 were found to be effective
      single-layer antireflection coatings for polymethylmethacrylate. In the range of
      400-700 nm, light transmittance of these lenses, when coated on both sides with
      perfluorobutene-2, was about 4% higher than with uncoated lenses. Also, the
      transmittance curve of the coated lenses was essentially flat from 400 nm to 700
      nm.

PMID- 20155197
TI  - Visual modeling of laser Doppler anemometer signals by moire fringes.
AB  - This report describes the employment of moire patterns to model visually
      interference phenomena in general and laser Doppler anemometer signals in
      particular. The modeling includes signals created in dual beam and reference beam
      anemometers by both single particles and particle pairs. The considerations are
      extended to visual modeling of multiparticle signals and the decay of signal
      quality in the presence of many particles. The fringe model of the laser Doppler
      anemometer is also considered, and moire patterns are employed to demonstrate the
      interference fringes in the crossover region of two intersecting laser beams.
      Gaussian beam properties are taken into account to allow the effects of
      improperly designed optical systems to be studied. Instructions for using
      computer generated transparencies to produce the different moire patterns are
      provided to allow the reader to study in detail the various interference
      phenomena described.

PMID- 20155198
TI  - Propagation of infrared light in flexible hollow waveguides.
AB  - Designs are described for flexible hollow waveguides with low ir loss over
      distances on the order of 1 m. Transmission losses at 10.6 microm are calculated,
      and the effect of bends and twists is discussed. A hollow combination metal
      dielectric-walled rectangular waveguide is proposed that can have transmission as
      high as 95% for a 1-m length, while bent with a 1-m radius of curvature.

PMID- 20155199
TI  - Optical waveguide refractive index profiles determined from measurement of mode
      indices: a simple analysis.
AB  - The WKB approximation is used to derive simple equations that predict the shape
      of the index profile from measured mode indices of a planar optical waveguide.
      This nondestructive test is a useful tool in the study of diffused guides. The
      index profile is assumed either to decrease monotonically from the surface or to
      be symmetrical in the case of a buried guide. The approximation uses straight
      line segments to connect the measured points. Results are compared with
      mathematical solutions for exponential, Fermi, and step distributions and with
      other independent experimental observations of the profile in a nickel-diffused
      LiNbO(3) guide.

PMID- 20155200
TI  - Bragg coupling efficiency for guided acoustooptic interaction in GaAs.
AB  - The guided acoustooptical interaction on the (100) plane of GaAs is investigated
      as a function of waveguide thickness type of mode, acoustic frequency, direction
      of acoustic wave propagation, and substrate refractive index Our calculated
      results indicate that best efficiency is obtained for TE(0) ? TE(0) optical modes
      and for acoustic surface wave propagating along the ?01l? direction at a
      waveguide thickness close to cut-off Under these conditions, approximately 75 mW
      of acoustic power is required for 100% diffraction. For a transducer aperture
      giving 50 Omega of radiation resistance, the rf bandwidth of the diffraction is
      limited essentially by the frequency bandwidth of the interdigital transducer. A
      comparison of the calculated results with experimental data at 1.06-microm
      optical wavelength is also given.

PMID- 20155201
TI  - Modes in misaligned unstable resonators.
AB  - A previously developed technique for the calculation of modes of perfectly
      aligned unstable resonators in the limit of large Fresnel number is here extended
      to include effects of misalignment. It is shown how asymptotic techniques may be
      employed to simplify the calculation of near- and far-field patterns produced by
      such modes. The basic conclusion is that rectangular aperture unstable resonators
      are quite insensitive to misalignment, in the sense that the lowest-loss mode
      continues to be essentially diffraction limited as long as the feedback mirror
      remains well within the output beam.

PMID- 20155202
TI  - Optical waveguide loaded with high refractive-index strip film.
AB  - Mode propagation and field distribution in a strip-loaded waveguide are analyzed
      for the case where the refractive index of the loading film is higher than that
      of the waveguide. It is found that the propagation constant is remarkably changed
      by loading the film with the thickness around the cutoff. As a result, the effect
      of the optical energy confinement below the strip film is large compared with the
      previously proposed case where the low-index film is loaded, and the use of the
      high refractive-index film as the loading strip is very attractive for
      constructing a three-dimensional waveguide structure.

PMID- 20155203
TI  - Laser beam scanning using computer-generated holograms.
AB  - A new laser grating scanner concept with attractive capabilities is described.
      The grating used in this scanner is a computer-generated hologram. The
      constructional parameters of this type of computer-generated hologram are
      discussed. In addition to achieving a laser beam deflection, the computer
      generated hologram can correct the curvature of the scanning beam. Experiments
      demonstrating the feasibility of this type of scanner in a drum and disk
      configuration are presented. Realization of two-dimensional scan patterns using
      computer-generated holograms is illustrated by experimental results.

PMID- 20155204
TI  - Mechanical vibrations: mapping their phase with hologram interferometry.
AB  - Generally, both the phase and amplitude of vibration of an object's surface vary
      from point to point. This paper details two methods for extracting vibrational
      phase information from the higher order fringes of holographic interferograms
      recorded by phase modulating either the object or reference illumination. Both
      methods require the superposition of only a few transparencies of interferograms
      in order to generate useful vibration-phase contour maps.

PMID- 20155205
TI  - Sandwich hologram interferometry. 3:Contouring.
AB  - This new holographic contouring method produces interference fringes formed by
      illumination shearing during recording in combination with observation shearing
      during reconstruction. One holographic plate is exposed after which the point
      source of light illuminating the object is displaced laterally to produce a shear
      of the illumination beam. A second exposure is made on another plate, whereupon
      the two plates are processed and bonded together with their emulsions outward.
      When this sandwich hologram is reconstructed, contouring fringes are formed that
      represent the intersection of the object by a set of interference surfaces. A
      tilt of the sandwich hologram produces a shear of the observation that results in
      a corresponding rotation of the intersecting surfaces of up to 180 degrees in
      every direction of the three-dimensional reconstructed object space. Thus, sign,
      direction, and magnitude of object slant can be evaluated by measuring the
      analogous sandwich tilt. The possibility of studying cross sections in any random
      orientation from a single sandwich hologram could be very useful for measuring
      and demonstration purposes.

PMID- 20155206
TI  - Cross-correlation discrimination for optical cavity modes.
AB  - Matched spatial filters were constructed for various modes of a spherical Fabry
      Perot interferometer (FPSI). The cross correlation between many of these modes
      was obtained experimentally as well as theoretically. The orthogonality between
      various modes was demonstrated and used in order to discriminate against all
      orthogonal modes. A discrimination funtion that predicts the performance of the
      matched-filtering process is defined and analytically evaluated for rectangular
      and cylindrical Gaussian modes. It is shown that arbitrary discrimination
      strength can be obtained at the sacrifice of output signal strength. It was
      experimentally demonstrated that a scanning FPSI used in conjunction with only
      one zero-order-mode filter could be used over nearly its entire domain of stable
      cavity spacings and still maintain a full (c/2L) free spectral range.

PMID- 20155207
TI  - Thermal blooming of a rapidly moving laser beam.
AB  - We have theoretically evaluated aspects of high speed thermal blooming and have
      found that refractive effects are negligible except for the case of a beam moving
      at transonic velocities. The density perturbation at Mach I is determined
      primarily by nonlinear flow field effects induced by heating of the atmosphere.
      Although the temperature perturbation is very small for a beam moving at sonic
      velocity, the density perturbation is not. It is approximately 2 orders of
      magnitude higher than the temperature perturbation. This large increase in the
      density perturbation is confined to a narrow range of Mach numbers that define a
      transonic flow in atmospheric propagation. Outside this transonic flow regime,
      thermal blooming is negligible.

PMID- 20155208
TI  - Continuous-wave (F + H(2)) chemical lasers: a temperature-dependent analytical
      diffusion model.
AB  - The development of an analytical model for predicting the performance of HF
      lasers that result from the mixing of atomic fluorine with molecular hydrogen in
      continuously flowing systems is described. The model combines a temperature
      dependent solution for a premixed laser system with laminar or turbulent flame
      sheet mixing schemes to generate closed-form expressions for the two conditions
      of constant pressure (simulating a free jet) and constant density (simulating a
      partially confined flow). The various approximations, including a fully
      communicating cavity and characteristic reaction and deactivation lifetimes, are
      discussed. Scaling laws that relate power to the total pressure and nozzle
      parameters are developed. Comparison with exact numerical treatments for a wide
      range of conditions reveals that the model is consistently accurate to ~10%.
      Finally, the sensitivity of the predictions to the kinetic rate package and the
      utility of the model for performing parameter studies are indicated.

PMID- 20155209
TI  - Goos-Hanchen shift.
AB  - An extremely simple derivation of the Goos-Hanchen shift is presented for total
      internal reflection at a plane interface between two semiinfinite dielectric
      media, as well as for optical waveguides of plane arid circular cross section.
      The derivation is based on energy considerations, requires knowledge of Fresnel's
      equation only, and shows explicitly that the shift is due to the flow of energy
      across the dielectric boundary.

PMID- 20155210
TI  - Optical fiber modes using stimulated four photon mixing.
AB  - Stimulated four photon mixing has been used to excite separately all the modes of
      a ten-mode optical fiber. Photographs were taken and the mode intensities scanned
      with a moving pinhole. Measured intensities were found to agree well with the
      intensities calculated for an ideal guide with an abrupt core-cladding interface.
      In addition a locking effect was observed in which two separate Stokes:anti
      Stokes pairs, which normally occur at slightly different frequency shifts from
      the pump, locked together at the same frequency.

PMID- 20155211
TI  - Optical access couplers and a comparison of multiterminal fiber communication
      systems.
AB  - Optical T and multiple T access couplers designed for tapped trunk line
      multiterminal communication systems that use bundles of multimode fibers as the
      transmission media have been investigated. The particular coupler designs tested
      used bent Pyrex rods for bifurcation and scrambling. Coupler throughput losses
      (not counting packing fraction losses) are 1.5-2.5 dB. The bent rod optical T and
      multiple T access couplers must be used with high N.A., low packing fraction loss
      fibers. To avoid the use of a repeater a multiple T or star configuration must be
      used in a system comprising ten or more terminals.

PMID- 20155212
TI  - Angle selective fiber coupler.
AB  - Angle selective input coupling through the side of a slightly tapered section of
      Corning highly multimode fiber has been experimentally demonstrated for the first
      time. This coupling technique allows the possibility of fabricating bidirectional
      (duplex) couplers for systems employing single strands of multimode, low loss
      fiber.

PMID- 20155213
TI  - Attenuation measurement in glasses for optical communications: an immersion
      method.
AB  - In fiber waveguides for optical communication losses of a few dB/km have been
      realized. To measure the attenuation in bulk glass rods, which are often used as
      starting material for fiber production, an accuracy of at least 1 dB/km is
      desirable. With the method reported, the losses were determined from transmission
      measurements on 3-cm long samples. To eliminate surface losses the samples were
      immersed in a liquid of about the same refractive index. For two types of
      synthetic vitreous silica-Suprasil 1 and Suprasil Wl-the attenuation was measured
      between 400 nm and 750 nm. These loss-spectra show that for Suprasil 1, with the
      exception of the region of OH absorption, the limit of the intrinsic losses of
      pure silica is reached, while Suprasil Wl shows considerably higher attenuation
      in the whole region. The measuring accuracy achieved so far was estimated to be
      about +/-1 dB/km.

PMID- 20155214
TI  - Vertical distribution of ozone: a new method of determination using satellite
      measurements.
AB  - A new method to determine the vertical distribution of atmospheric ozone over a
      wide range from the spectral measurement of backscattered solar uv radiation is
      proposed. Equations for the diffuse reflection in an inhomogeneous atmosphere are
      introduced, and some theoretical approximations are discussed. An inversion
      equation is formulated in such a way that the change of radiance at each
      wavelength, caused by the minute relative increment of ozone density at each
      altitude, is obtained exactly. The equation is solved by an iterative procedure
      using the weight function obtained in this work. The results of computer
      simulation indicate that the ozone distribution from the mesopause to the
      tropopause can be determined, and that although it is impossible to suggest
      exactly the complicated profile with fine structure, the smoothed ozone
      distribution and the total content can be determined with almost the same
      accuracy as the accuracies of measurement and theoretical calculation of the
      spectral intensity.

PMID- 20155215
TI  - Remote sensing of chlorophyll in an atmosphere-ocean environment: a theoretical
      study.
AB  - A Monte Carlo program was written to compute the effect of chlorophyll on the
      ratio of upwelling to down-welling radiance and irradiance as a function of
      wavelength, height above the ocean, and depth within the ocean. This program
      simulates the actual physical situation, since a real atmospheric model was used,
      i.e., one that contained both aerosol and Rayleigh scattering as well as ozone
      absorption. The complete interaction of the radiation field with the ocean was
      also taken into account. The chlorophyll was assumed to be uniformly mixed in the
      ocean and was also assumed to act only as an absorbing agent. For the ocean model
      both scattering and absorption by hydrosols was included. Results have been
      obtained for both a very clear ocean and a medium turbid ocean. Recommendations
      are made for optimum techniques for remotely sensing chlorophyll both in situ and
      in vitro.

PMID- 20155216
TI  - Using Statewide Youth Surveys to Evaluate Local Drug Use Policies and
      Interventions.
AB  - This article summarizes two studies that use statewide school-based youth surveys
      to evaluate local initiatives to reduce alcohol and other substance abuse. The
      Vermont "New Directions" evaluation was conducted to assess the effects of a
      community-based intervention in 23 Vermont communities to reduce youth substance
      use. Outcome data were obtained from the Youth Risk Behavior Survey, which is
      administered to students in grades 8 through 12 every other year in almost all
      school districts in the state. Based on a quasi-experimental design, results
      indicated significant declines in cigarette and marijuana use in intervention
      districts relative to comparison districts during the study period, and led to
      legislative action to continue funding the initiative. The Oregon "Reducing Youth
      Access to Alcohol" study is now being conducted in 36 Oregon communities (45
      school districts) with a randomized controlled design to evaluate six combined
      environmental strategies to reduce underage drinking. The strategies include a
      reward and reminder program and minor decoy operations to reduce commercial
      alcohol availability, party patrol dispersal and minor in possession arrests to
      reduce social alcohol availability, traffic emphasis, and media advocacy to
      increase visibility of policy enforcement activities. The Oregon Healthy Teens
      Survey has been administered in a large number of Oregon school districts
      annually since 2000 and is being used to assess intervention effects on alcohol
      availability, underage drinking and alcohol-related problems such as DUI. These
      studies illustrate how established statewide youth surveys offer important
      advantages for evaluating local substance abuse prevention policies and
      interventions.

PMID- 20155217
TI  - The Year's New Drugs & Biologics - 2009.
AB  - This annual article presents new drugs and biologics that were launched or
      approved for the first time during the previous year. In 2009, 51 new medicines
      and vaccines reached their first markets. Line extensions (new indications, new
      formulations and new combinations of previously marketed products) accounted for
      more than 30% of the new products launched in 2009. In addition to providing an
      overview of all drugs and biologics launched or approved for the first time ever
      in the previous year, this article will also review in further depth the first-in
      class drugs launched for the first time last year, providing a better
      understanding of their novel mechanisms of action; an analysis of the discovery
      and development periods for the year's new products; and a comprehensive overview
      of drug repositioning as a strategy for extending the life spans of medicines. We
      also provide a brief glimpse at selected drugs and biologics which could reach
      their first markets in the foreseeable future.

PMID- 20155218
TI  - Accelerating drug development and approval.
AB  - Regulatory agencies are the gateway between the pharma/biotech industry and
      patients and can serve as stimulators of new drug development. This article
      highlights several means of doing so implemented thus far, many with already
      impressive histories, such as orphan drug legislation, and others of a more
      experimental nature, such as the FDA's priority review voucher program. These
      initiatives represent different approaches to finding treatments for rare and
      widespread but neglected diseases, as well as speeding the development process
      for pharmaceutical and biological agents more generally. Commercial incentives,
      streamlined regulatory processing, exploratory trial designs, research assistance
      and cash infusions are all means of promoting drug development being explored in
      the United States, Europe and beyond. In some cases, such as fast track
      designation and priority review vouchers, regulatory agencies have turned their
      own processes into incentives, offering advantageous alternative routes to
      product approval, like a faster lane on the highway for vehicles carrying
      multiple passengers. In 2009, regulatory agencies and the governments they
      represent also had to confront two tremendous challenges: the global recession
      and the H1N1 influenza virus pandemic. These tests have been met with increased
      funding in the former case and coordinated efforts to develop, approve and
      stockpile H1N1 vaccines in the latter.

PMID- 20155219
TI  - Overcoming the obstacles in the pharma/biotech industry: 2009 update.
AB  - The research-based biopharmaceutical industry faced new challenges during 2009,
      many rooted in the global economic recession, which further complicated a
      situation that was already characterized by the obstacles traditionally debated
      in this and other publications: generic competition, patent expirations and
      accusations of declining innovation. Once again, companies have been forced to
      seek out new strategies (mergers, acquisitions, licensing deals, offshore
      clinical testing and more) in order to cut costs and fill the gaps in their R&D
      pipelines. However, it is conceivable that the existing R&D model has limitations
      that can no longer be overcome via these traditional strategies and that the time
      has come for an entirely new model.

PMID- 20155220
TI  - Research paths to successful prevention and treatment of swine-derived H1N1
      influenza virus infection.
AB  - Despite the fact that the threat of a new influenza pandemic has been hovering
      over us for quite some time, the truth is that the weapons currently licensed for
      fighting the swine-derived H1N1 virus are not quite up to the current needs.
      Although considerable effort has been put into developing new vaccines and
      antivirals, the available agents are basically the same ones as 10 years ago. In
      this review, we consider novel prophylactic and therapeutic alternatives, which
      luckily are being proposed by experts in the field. The better understanding and
      basic knowledge of influenza viruses, including their high variability and
      potential for antigenic drift, has prompted the development of new antivirals and
      more efficacious vaccines that hold promise for the near future.

PMID- 20155221
TI  - European Medicines Agency support mechanisms fostering orphan drug development.
AB  - A legislative framework introducing European public health measures on orphan
      medicinal products came into force in the European Union in April 2000. The aim
      of the orphan legislation is to stimulate research and development of medicinal
      products for rare diseases by providing incentives to the sponsors. Incentives
      include, among others, an unreserved access to the centralized procedure with a
      10-year period of market exclusivity and fee reductions including free scientific
      advice for drug development. Nine years after the implementation of the orphan
      legislation, more than 690 products have been designated and 58 have received
      marketing authorizations in Europe. The orphan designations granted to date cover
      a wide variety of diseases for which there are either no authorized treatments or
      only limited treatment options with a need for improvement. At the dawn of the
      tenth anniversary of the orphan legislation, the aim of this article is to review
      how the European Medicines Agency has supported the mechanisms fostering
      development of orphan medicines in the E.U. since 2000.

PMID- 20155222
TI  - Biomarker update for breast, colorectal and non-small cell lung cancer.
AB  - The integration of diagnostics into the selection, administration, dosing and
      monitoring of the use of anticancer drugs has continued to impact the
      pharmaceutical industry with particular emphasis on cancers of the breast, colon
      and lung. An update is given on the biomarkers for these cancers.

PMID- 20155224
TI  - Adhesion performance of new hydrolytically stable one-component self-etching
      enamel/dentin adhesives.
AB  - PURPOSE: To demonstrate that hydrolytically stable methacrylamide monomers allow
      one-component self-etching adhesives with comparable adhesive properties and
      better storage stability than hitherto available methyacrylate-based adhesive
      formulations. MATERIALS AND METHODS: The shear bond strength and storage
      stability of the new one-component self-etching, methacrylamide-based adhesive
      AdheSE One F (Ivoclar Vivadent) to enamel and dentin was compared to the
      methacrylate-based Clearfil S3 Bond (Kuraray), G-Bond (GC), Hybrid Bond (Sun
      Medical), iBond (Heraeus Kulzer), Optibond All In One (Sybron-Kerr), and the
      methacrylamide-based Xeno V (Dentsply). Hydrolytic stability and adhesive
      performance of these adhesives was evaluated by accelerated aging at 42 degrees C
      over 16 weeks and monthly assessment of shear bond strength to dentin. The null
      hypothesis was that the bond strength of one-bottle self-etching dental adhesives
      is independent of storage duration and that, disregarding their higher stability
      against hydrolysis, methacrylamide- based materials offer performance beyond
      shelf-life time, comparable to methacrylate-based adhesives. Statistical analysis
      included 1-way-ANOVA and the Tukey-B post-hoc test (p < 0.05). RESULTS: Shear
      bond strengths on enamel ranged from 32.7 MPa (AdheSE One F) to 16.6 MPa (iBond)
      and on dentin from 36.1 MPa (Optibond All In One) to 20.5 MPa (G-Bond). During
      accelerated aging, methacrylate-based adhesives with a pH < 2 exhibited
      decreasing bond strengths over time with material-dependent losses of up to 68%
      (Hybrid Bond, 8 weeks, 42 degrees C). Under the same conditions, the
      methacrylamide-based formulations AdheSE One F and Xeno V were stable for 16
      weeks regarding shear bond strength to dentin. CONCLUSIONS: The shelf life of one
      component self-etching adhesives is determined by their chemical composition. In
      conventional methacrylate-based adhesives, the inherently acidic environment of
      such formulations leads to monomer degradation due to hydrolysis. In contrast,
      methacrylamide-based adhesives are stable to aqueous acid and exhibit much
      superior storage stability without monomer degradation-related losses in adhesion
      performance.

PMID- 20155225
TI  - The influence of a local anesthetic containing vasoconstrictor on microtensile
      bond strengths of two adhesive systems to human dentin in situ.
AB  - PURPOSE: To evaluate the bond strengths of an etch-and-rinse adhesive and a self
      etching adhesive to human dentin in vitro and under two in situ conditions: non
      anesthetization and anesthetization of the teeth with a local anesthetic
      containing vasoconstrictor. MATERIALS AND METHODS: An in situ study was performed
      on 49 maxillary premolars scheduled for extraction due to orthodontic reasons.
      For the bond strength test, occlusal cavities were prepared either with or
      without a local anesthetic containing vasoconstrictor. The cavities were bonded
      with Adper Single Bond or Clearfil SE Bond and filled with a resin composite,
      Filtek Z250. The teeth were then extracted, sectioned, trimmed, and tested for
      microtensile bond strength. For the observation of dentin surfaces, 20 premolars
      were used. The impressions of the cavity floors in the anesthetized and non
      anesthetized groups were taken before and after acid etching. The replicas were
      observed under a scanning electron microscope. In vitro, the bond strength test
      and the SEM observation were also carried out on 24 extracted premolars with the
      same procedures used in the in situ study. RESULTS: The bond strengths of the two
      adhesives bonded to dentin in situ were significantly lower than those in vitro.
      When both adhesives were tested under in situ conditions, there were no
      significant differences between the bond strengths to dentin of anesthetized and
      non-anesthetized groups (p > 0.05). No fluid droplets were found on dentin on the
      cavity floor prepared in vitro, either before or after acid-etching. For the
      unetched dentin prepared in situ, fluid droplets were found and covered on the
      smear layer in anesthetized and non-anesthetized groups, but the droplets were
      slightly larger in the non-anesthetized group. In the non-anesthetized, acid
      etched group, dentin surfaces were covered with coalescent dentinal fluid in most
      specimens. However, in the anesthetized, acid-etched group, patent tubules and
      some dentinal fluid were observed on the surfaces. CONCLUSION: It was concluded
      that in situ, dentinal fluid had a detrimental effect on the dentin bond
      strengths of an etch-and-rinse adhesive and a self-etching adhesive. However,
      reduction in dentinal fluid due to the effect of a local anesthetic containing
      vasoconstrictor did not improve the bond strengths in either adhesives.

PMID- 20155226
TI  - Bond efficacy and interface morphology of self-etching adhesives to ground
      enamel.
AB  - PURPOSE: This study compared the microshear bond strengths to ground enamel of
      three one-step self-etching adhesive systems, a self-etching primer system and an
      etch-and-rinse adhesive system. MATERIALS AND METHODS: Three self-etching
      adhesives, Futurabond DC (Voco), Clearfil S Tri Bond (Kuraray) and Hybrid bond
      (Sun-Medical), a self-etching primer, Clearfil SE Bond (Kuraray), and an etch-and
      rinse system, Admira Bond (Voco), were selected. Thirty human molars were used.
      The root of each tooth was removed and the crown was sectioned into halves. The
      convex enamel surfaces were reduced by polishing on silicone paper to prepare a
      flat surface. The bonding systems were applied on this surface. Prior to adhesive
      curing, a hollow cylinder (2.0 mm height/0.75 mm internal diameter) was placed on
      the treated surfaces. A resin composite was then inserted into the tube and
      cured. After water storage for 24 h, the tube was removed and shear bond strength
      was determined in a universal testing machine at a crosshead speed of 0.5 mm/min.
      The results were analyzed with ANOVA and the Tukey.-Kramer test at a 59 degrees
      confidence level. The enamel of five additional teeth was ground, and the etching
      component of each adhesive was applied and removed with absolute ethanol instead
      of being light cured. These teeth and selected fractured surfaces were examined
      by SEM. RESULTS: Adhesion to ground enamel of the Futurabond DC (25 +/- 3.5 MPa)
      and Clearfil SE Bond (23 +/- 2.9 MPa) self-etching systems was not significantly
      different from the etch-and-rinse system Admira Bond (27 +/- 2.3 MPa). The two
      self-etching adhesives Clearfil S Tri bond and Hybrid Bond demonstrated
      significantly lower bond strengths (14 +/- 1.4 MPa; 11 +/- 1.9 MPa) with no
      significant differences between them (p < 0.05). CONCLUSION: Bond strengths to
      ground enamel of self-etching adhesive systems are dependent on the type of
      adhesive system. Some of the new adhesive systems showed bond strength values
      comparable to that of etch-and-rinse systems. There was no correlation between
      bond strength and morphological changes in enamel.

PMID- 20155227
TI  - Effect of chlorhexidine application in a self-etching adhesive on the immediate
      resin-dentin bond strength.
AB  - PURPOSE: To investigate whether the application of chlorhexidine in a two-step
      self-etching adhesive has an adverse effect on the immediate resin-dentin bond
      strength. MATERIALS AND METHODS: Different amounts of 20 wt% chlorhexidine
      digluconate were added directly to the Clearfil SE Bond primer to prepare
      mixtures of 4 different concentrations of chlorhexidine: 0.05 wt%, 0.1 wt%, 0.5
      wt%, and 1.0 wt%. Sixteen extracted third molars were randomly divided into 4
      groups. Each group corresponded to one of the 4 chlorhexidine concentrations.
      Each of the 16 teeth was sectioned into halves. One half was customarily bonded
      with Clearfil SE Bond without chlorhexidine, and the other half was bonded with
      Clearfil SE Bond containing different concentrations of chlorhexidine.
      Microtensile bond strengths were tested immediately after specimen preparation.
      The modes of fractures were examined under a stereomicroscope. RESULTS: No
      significant difference of immediate resin-dentin bond strength was observed
      between the control groups and any of the experimental groups containing
      chlorhexidine (p > 0.05). CONCLUSION: The addition of chlorhexidine to a two-step
      self-etching adhesive primer (Clearfil SE Bond primer) has no adverse effect on
      the immediate resin-dentin bond strength when the chlorhexidine concentration in
      the primer is lower than or equal to 1.0 wt%.

PMID- 20155229
TI  - Water sorption and solubility of four self-etching, self-adhesive resin luting
      agents.
AB  - PURPOSE: To evaluate and compare the water sorption and water solubility of four
      self-etching, self-adhesive resin luting agents. MATERIALS AND METHODS: Four self
      etching, self-adhesive resin luting agents (RelyX Unicem, Maxcem, Biscem,
      Multilink Sprint) and one classic resin luting agent (Multilink Automix) as a
      control group were used. Twelve disks (8 mm x 1 mm) of each material were
      prepared according to ISO 4049. Water sorption and solubility were calculated,
      using the formulae which the ISO 4049 specification provides. RESULTS: Maxcem and
      Biscem were found to have very high water sorption values. RelyX Unicem and
      Multilink Sprint exhibited water sorption values only slightly higher than the
      control group. Regarding water solubility, the greater mass loss was found for
      Maxcem. Multilink Sprint exhibited no mass change. Biscem was found to have low
      solubility values, whereas RelyX Unicem and Multilink Automix exhibited negative
      solubility. CONCLUSION: Multilink Sprint and RelyX Unicem were found to comply
      with the ISO requirements regarding water sorption and solubility, while Maxcem
      and Biscem did not. Materials of the same group exhibited very different behavior
      during their interaction with water.

PMID- 20155228
TI  - Degree of conversion and antimicrobial activity of etch-and-rinse versus self
      etching adhesives.
AB  - PURPOSE: This study was designed to compare the self-etching with the etch-and
      rinse adhesives regarding the degree of conversion and antimicrobial activity
      against cariogenic bacteria. MATERIALS AND METHODS: The materials used were
      AdheSE (two-step self-etching), Adper Prompt L-Pop (self-etching, single-step)
      and Excite (etch-and-rinse) adhesives. The degree of conversion was measured
      using Fourier Transformation Infrared Spectroscopy. The absorbance peaks of
      infrared rays by the aliphatic C=C was detected at 1632 to 1637cm-1 and the
      aromatic C=C peak at 1610 to 1500 cm-1.The antimicrobial activity was evaluated
      using the microorganisms Streptococcus mutans, Lactobacillus salivarius, and
      Actinomyces odontolyticus, with a disk diffusion method. Chlorhexidine
      digluconate solution 0.2% was used as a positive control. Zones of inhibited
      bacterial growth were observed and measured. RESULTS: AdheSE showed the highest
      degree of conversion, followed by Excite, while Adper Prompt L-Pop had the lowest
      values. A significant difference in the degree of conversion was found between
      Excite and Adper Prompt L-Pop as well as AdheSE and Adper Prompt L-Pop. On the
      other hand, there was no significant difference between Excite and AdheSE. Adper
      Prompt L-Pop showed an antimicrobial effect against Streptococcus mutans and
      Actinomyces odontolyticus while it was unable to inhibit the growth of
      Lactobacillus salivarius. AdheSE could inhibit the growth of Streptococcus mutans
      only. Excite did not produce inhibition zones to the tested microorganisms.
      CONCLUSION: Adper Prompt L-Pop showed the worst degree of conversion. AdheSE and
      Excite had the highest degree of conversion. Appreciable antimicrobial activity
      was noted with self-etching adhesives, while the etch-and-rinse demonstrated no
      antimicrobial action.

PMID- 20155230
TI  - Restoring strength of incisors with veneers and full ceramic crowns.
AB  - PURPOSE: The aim was to determine the in vitro fracture resistance of incisors
      restored with veneers and full ceramic crowns compared to unrestored teeth.
      MATERIALS AND METHODS: Seventy intact, extracted human maxillary central incisors
      were randomized and assigned to 7 groups (n = 10). The teeth in group 1 remained
      intact (control). The teeth in groups 2 to 6 were prepared and IPS Empress
      restorations were conditioned and bonded using an adhesive luting cement,
      Variolink II/Syntac (group 2: labial veneer with incisal overlap, group 3: 3/4
      veneer with margin in enamel, group 4: 3/4 veneer with margin in dentin, group 5:
      crown with margin in enamel, group 6: crown with margin in dentin group 7: veneer
      on worn tooth. After finishing and polishing, specimens were stored in water and
      thermocycled for 2000 cycles between 5 degrees C and 55 degrees C. The maximal
      fracture load of the specimens (40-degree inclination) was determined using the
      universal testing machine (Zwick) at a constant crosshead speed (0.5 mm/min). The
      statistical analysis was performed using the Kruskal-Wallis test with Bonferroni
      correction (p < 0.05). Fracture surfaces were qualitatively analyzed by SEM.
      RESULTS: All restored teeth with cervical preparation margins in enamel showed a
      fracture load not significantly different from the intact teeth (control).
      Restored teeth with cervical preparation margins in dentin showed a significantly
      lower fracture load. All restorations showed a fracture load far above 400 N,
      serving as functional reference for anterior teeth. The failures were
      predominantly cohesive. CONCLUSION: For the restoration of tooth strength,
      defining the finishing lines of veneers and crowns in enamel is recommended.
      Restorations with finishing lines in dentin resulted in significant loss of
      strength. Three-quarter veneers with finishing lines in enamel are functionally
      equal to crowns with the advantage of conserving tooth structure.

PMID- 20155231
TI  - Benefits of a two-step cementation procedure for prefabricated fiber posts.
AB  - PURPOSE: To determine whether two-step cementation of prefabricated fiber posts
      leads to higher bond strengths. MATERIALS AND METHODS: Forty-eight human canine
      teeth were divided into six groups and fiber posts were cemented with DC Core,
      RelyX Unicem and Panavia F2.0, according to a one-step or two-step procedure. Per
      root, four cross-sections were prepared. The differences in push-out strength
      between procedure, cement and location within the root were determined. RESULTS:
      For all cements, the push-out strengths for the two-step procedure were
      significantly higher than for the one-step procedure (p < 0.001). Differences
      between the cements for both the one-step and two-step procedure were not
      statistically significant (p = 0.05). CONCLUSION: The reduction of the C-factor
      by means of a two-step cementation, a procedure equivalent to the layering
      technique of composite restorations, resulted in significantly higher bond
      strengths. The increase of 60% in bond strength may be beneficial to the
      retention of post and core restorations.

PMID- 20155232
TI  - Bonding strategies to pulp chamber dentin treated with different endodontic
      irrigants: microshear bond strength testing and SEM analysis.
AB  - PURPOSE: To evaluate the effect of 6 irrigant regimens on the microshear bond
      strength of different adhesives to pulp chamber dentin and to determine their
      interfacial morphology by SEM. MATERIALS AND METHODS: Forty-three human molars
      were split into halves and ground to provide flat pulp chamber dentin. Eighty
      five halves were used. The specimens were assigned to 6 groups according to the
      irrigant regimen used. Group I (n=10) was irrigated with distilled water
      (control). The remaining 5 groups (n=15 each) were irrigated with 5.25% NaOCl
      followed by either 5.25% NaOCl, 17% EDTA, benzalkonium chloride (Tubilcid Plus)
      or MTAD (Biopure), either rinsed or not. Irrigated specimens were bonded using
      Clearfil S3 Bond or Adper Single Bond 2, which was employed with or without
      etching. Resin composite cylinders were bonded using tygon tubes for microshear
      bond strength testing. Data were analyzed using two-way ANOVA followed by Tukey's
      post-hoc test. Representative specimens of each group were prepared from 17
      further molars for interfacial SEM examination. RESULTS: The different irrigant
      regimens used did not significantly alter the microshear bond strength values
      using either of the bonding systems, except NaOCl, which significantly reduced
      the microshear bond strength values with Adper Single Bond 2. Bonding irrigated
      specimens directly using the Adper Single Bond 2 without prior etching provided
      significantly reduced values. CONCLUSION: The irrigant regimens examined could be
      used safely prior to bonding except for the NaOCl, which should be negated if it
      is to be followed by Adper Single Bond 2, and the etching step cannot be omitted
      if an etch-and-rinse adhesive system is the adhesive of choice.

PMID- 20155233
TI  - Long-term provisional anterior tooth replacement using fiber-reinforced composite
      and avulsed tooth crowns as pontics.
AB  - The loss of anterior teeth due to trauma requires immediate attention for
      function and esthetics. While implant- supported or conventional fixed prostheses
      may be the treatments of choice for adults, relatively noninvasive and reversible
      provisional procedures for tooth replacement are necessary for adolescents. In
      recent years, developments in fiber and composite technology offer a conservative
      treatment approach to restore the anterior edentulous space as a fixed
      provisional tooth replacement. This case report presents the chairside procedures
      of anterior tooth replacement in an adolescent using the avulsed tooth crowns as
      pontics which were bonded to teeth on either side of the edentulous space and
      reinforced with a preimpregnated fiber.

PMID- 20155234
TI  - Editorial: Evaluation of the project P.A.T.H.S. in Hong Kong: are the findings
      replicable across different populations?
AB  - Existing youth enhancement programs commonly deal with isolated problems and
      issues in adolescent development and they are relatively short-term in nature. To
      promote holistic development among adolescents in Hong Kong, we launched Positive
      Adolescent Training through Holistic Social Programmes (P.A.T.H.S.). One unique
      characteristic of the Project P.A.T.H.S. is systematic evaluation of the program
      using various evaluation strategies. In this special issue, comprising 8 research
      articles, we have applied the principle of replication to re-evaluate the
      effectiveness of the Programs, including subjective outcome evaluation based on
      program participants and implementers, evaluation based on secondary data
      evaluation, and objective outcome evaluation. Generally speaking, the findings
      are consistent with those reported previously, thus providing evidence for the
      replication of related research findings. These replicated findings generally
      suggest that different stakeholders have positive perceptions of the program,
      workers and benefits of the program and there is evidence supporting the
      effectiveness of the program.

PMID- 20155235
TI  - Objective outcome evaluation of the project P.A.T.H.S. in Hong Kong: findings
      based on individual growth curve models.
AB  - The Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training
      through Holistic Social Programmes) is a curricular-based program that attempts
      to promote positive youth development in Hong Kong. In the second year of the
      Full Implementation Phase, 20 experimental schools (n = 2,784 students) and 23
      control schools (n = 3,401 students) participated in a randomized group trial.
      Analyses based on linear mixed models via SPSS showed that participants in the
      experimental schools displayed better positive youth development than did
      participants in the control schools based on different indicators derived from
      the Chinese Positive Youth Development Scale. Differences between experimental
      and control participants were also found when students who joined the Tier 1
      Program and perceived the program to be beneficial were employed as participants
      of the experimental schools.

PMID- 20155236
TI  - Subjective outcome evaluation of a positive youth development program in Hong
      Kong: profiles and correlates.
AB  - Secondary school students (n = 33,867 from 213 secondary schools) responded to a
      subjective outcome evaluation form to assess their views of the program, workers
      (teachers and/or social workers), and perceived effectiveness of the program.
      Results showed that high proportions of the respondents had positive perceptions
      of the program and the instructors, and more than four-fifths of the respondents
      regarded the program as helpful to them. While schools admitting students with
      different academic abilities and hours did not differ in the subjective outcome
      evaluation ratings, subjective evaluation ratings for workers were highest,
      followed by ratings for the program and perceived effectiveness. The present
      study replicates the previously reported findings and provides additional support
      for the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. (Positive
      Adolescent Training through Holistic Social Programmes) in Hong Kong.

PMID- 20155237
TI  - Subjective outcome evaluation of the project P.A.T.H.S: descriptive profiles and
      correlates.
AB  - A total of 196 schools participated in the Tier 1 Program (Secondary 2
      curriculum) of the Project P.A.T.H.S. (Positive Adolescent Training through
      Holistic Social Programmes) in Hong Kong. After the completion of the program,
      1,178 instructors completed a subjective outcome evaluation form in order to
      assess their views of the program, instructors, and perceived effectiveness of
      the program. Results showed that high proportions of the instructors had positive
      perceptions of the program (range: 76.79-93.69%) and their own performance
      (range: 83.20-98.60%), and most of the respondents (range: 78.45-92.43%) regarded
      the program as helpful to the program participants. While the ratings in some
      items in the present findings were relatively better than those in the
      Experimental Implementation Phase, they were similar to those based on the
      Secondary 1 curriculum. Consistent with previous studies, the ratings on the
      program, instructors, and perceived effectiveness were significantly correlated.

PMID- 20155239
TI  - Secondary data analyses of conclusions drawn by the program implementers of a
      positive youth development program in Hong Kong.
AB  - The Tier 2 Program of the Project P.A.T.H.S. (Positive Adolescent Training
      through Holistic Social Programmes) is designed for adolescents with significant
      psychosocial needs, and its various programs are designed and implemented by
      social workers (program implementers) for specific student groups in different
      schools. Using subjective outcome evaluation data collected from the program
      participants (Form C) at 207 schools, the program implementers were asked to
      aggregate data and write down five conclusions (n = 1,035) in their evaluation
      reports. The conclusions stated in the evaluation reports were further analyzed
      via secondary data analyses in this study. Results showed that the participants
      regarded the Tier 2 Program as a success, and was effective in enhancing self
      understanding, interpersonal skills, and self-management. They liked the
      experiential learning approach and activities that are novel, interesting,
      diversified, adventure-based, and outdoor in nature. They also liked instructors
      who were friendly, supportive, well-prepared, and able to bring challenges and
      give positive recognition. Most of the difficulties encountered in running the
      programs were related to time constraints, clashes with other activities, and
      motivation of participants. Consistent with the previous evaluation findings, the
      present study suggests that the Tier 2 Program was well received by the
      participants and that it was beneficial to the development of the program
      participants.

PMID- 20155238
TI  - Subjective outcome evaluation based on secondary data analyses: the project
      P.A.T.H.S. in Hong Kong.
AB  - The intent of this study was to evaluate the program effectiveness of the Project
      P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes)
      (Secondary 1 Curriculum) by analyzing 207 school-based program reports, in which
      program implementers were invited to write down five conclusions based on an
      integration of the subjective outcome evaluation data collected from the program
      participants and program implementers. Secondary data analyses were conducted and
      1,855 meaningful units were extracted from 1,035 "aggregated" conclusions. Among
      them, about 27 and 18% were related to perceptions of the program and
      implementers, respectively, and most of them were positive in nature. About one
      third was related to perceived effectiveness of the program, and most of them
      referred to enhancement of students' development in societal, familial,
      interpersonal, and personal aspects. However, difficulties encountered during
      program implementation (3.34%) and recommendations for improvement (18.11%) were
      also reported. The present study replicated the findings reported in previous
      studies and suggests that the Tier 1 Program of the Project P.A.T.H.S. is
      beneficial to the development of the program participants.

PMID- 20155240
TI  - Subjective outcome evaluation findings: factors related to the perceived
      effectiveness of the tier 2 program of the project P.A.T.H.S.
AB  - After completion of the Tier 2 Program of the Project P.A.T.H.S. (Positive
      Adolescent Training through Holistic Social Programmes), 8,489 participants in
      196 schools responded to the Subjective Outcome Evaluation Form (Form C) to
      assess their views of the program, program workers, and perceived effectiveness
      of the program. Four major program elements were identified, including programs
      based on the adventure-based counseling approach (n = 48), programs concentrated
      on volunteer training and services (n = 44), programs with both the adventure
      based counseling approach and volunteer training activities (n = 63), and other
      programs with different foci (n = 41). Descriptive statistics showed that the
      respondents had positive perceptions of the program, workers, and benefits of the
      program. Perceived qualities of the program and the program workers were
      positively associated with perceived effectiveness of the program. Multiple
      regression analysis revealed that perceived qualities of the program, but not the
      program workers, predicted perceived effectiveness of the program. The
      theoretical and practical implications of the findings are discussed.

PMID- 20155241
TI  - Positive youth development programs targeting students with greater psychosocial
      needs: a replication.
AB  - The Tier 2 Program of the Project P.A.T.H.S. (Positive Adolescent Training
      through Holistic Social Programmes) targets adolescents with greater psychosocial
      needs, and the related programs were designed and implemented by school social
      workers. After completion of the Tier 2 Program (Secondary 1 Level), 9,931
      participants in 212 schools responded to the Subjective Outcome Evaluation Form
      (Form C) in order to assess their views of the program, workers, and perceived
      effectiveness of the program. Based on the consolidated reports submitted by the
      agencies to the funding body, the research team aggregated the consolidated data
      to form a "reconstructed" overall profile on the perceptions of the program
      participants. Four major types of program were identified, including programs
      based on the adventure-based counseling approach (n = 58), programs concentrating
      on volunteer training and services (n = 31), programs offering both adventure
      based counseling and volunteer training activities (n = 91), and other programs
      with different foci (n = 32). Results showed that high proportions of the
      respondents had positive perceptions of the programs and the workers, and over
      four-fifths of the respondents regarded the program as helpful to them. The
      present study provides support for the effectiveness of the Tier 2 Program of the
      Project P.A.T.H.S. in Hong Kong for the Full Implementation Phase.

PMID- 20155242
TI  - [Nitrous oxide production by the German Armed Forces in the 20th century :
      History of medicine and pharmacy in the Armed Forces].
AB  - The nitrous oxide production unit of the German Armed Forces was a worldwide
      unique facility which was only employed in the former main medical depot at
      Euskirchen (nitrous oxide: medical gas which is now obsolete). The last unit was
      phased out in 2002 and brought to the main medical depot at Blankenburg.
      Unfortunately the unit is now no longer in the depot and seems to have
      disappeared. This article describes the nitrous oxide production process and the
      use of the production unit which was designed by the Socsil company of
      Switzerland.

PMID- 20155243
TI  - [Negative and positive suggestions in anaesthesia : Improved communication with
      anxious surgical patients].
AB  - In extreme situations, for example during emergencies or when facing surgery,
      patients exhibit heightened and focused attention and increased susceptibility to
      suggestion. In this trance-like state negative suggestion, usually spoken
      unintentionally can aggravate anxiety, stress and pain. On the other hand words
      can offer an opportunity to benefit the patient via positive suggestion. In order
      to improve communication with anxious patients during stressful and painful
      medical procedures, certain hypnotherapeutic insights and methods can be
      employed, such as utilization, reframing, indirect suggestion, safe place,
      dissociation, metaphors, posthypnotic instructions and non-verbal communication
      and this without requiring formal hypnotic induction and without need for
      additional time, premises or personnel. Indications for such approaches are the
      preoperative visit, induction of anaesthesia, as well as operations under local
      or regional anaesthesia. An extreme example of the latter is awake craniotomy
      employing cranial nerve blocks and an awake-awake technique avoiding centrally
      acting drugs. Such hypnotic communication can help the patient to regain self
      control and access to inner resources.

PMID- 20155244
TI  - [Execution of analgesia and anesthesia procedures in obstetrics : Second revised
      recommendations of the German Society for Anesthesiology and Intensive Care
      Medicine and the Professional Association of German Anesthetists in cooperation
      with the German Society for Gynecology and Obstetrics].
AB  - While guidelines represent systematically developed aids for decision-making on
      appropriate courses of action, recommendations should focus the attention of the
      medical profession on noteworthy circumstances which are in need of amendment.
      The new recommendations on the "Execution of analgesia and anesthesia procedures
      in obstetrics" of the German Society for Anesthesiology and Intensive Care
      Medicine (Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin, DGAI)
      and the Professional Association of German Anesthetists (Berufsverband Deutscher
      Anasthesisten, BDA) in cooperation with the German Society for Gynecology and
      Obstetrics (Deutsche Gesellschaft fur Gynakologie und Geburtshilfe, DGGG)
      comprehensively fulfill these requirements. The new recommendations include not
      only revisions in the form of updating but also supplementations in the form of
      the new chapters "Initial care of newborns", "Postpartum hemorrhaging" and
      "Morbid obesity". In the following article relevant alterations to newly
      formulated or completely amended sections with consequences for the clinical
      practice will be discussed.

PMID- 20155245
TI  - Association of barley photoperiod and vernalization genes with QTLs for flowering
      time and agronomic traits in a BC2DH population and a set of wild barley
      introgression lines.
AB  - The control of flowering time has important impacts on crop yield. The variation
      in response to day length (photoperiod) and low temperature (vernalization) has
      been selected in barley to provide adaptation to different environments and
      farming practices. As a further step towards unraveling the genetic mechanisms
      underlying flowering time control in barley, we investigated the allelic
      variation of ten known or putative photoperiod and vernalization pathway genes
      between two genotypes, the spring barley elite cultivar 'Scarlett' (Hordeum
      vulgare ssp. vulgare) and the wild barley accession 'ISR42-8' (Hordeum vulgare
      ssp. spontaneum). The genes studied are Ppd-H1, VRN-H1, VRN-H2, VRN-H3, HvCO1,
      HvCO2, HvGI, HvFT2, HvFT3 and HvFT4. 'Scarlett' and 'ISR42-8' are the parents of
      the BC(2)DH advanced backcross population S42 and a set of wild barley
      introgression lines (S42ILs). The latter are derived from S42 after backcrossing
      and marker-assisted selection. The genotypes and phenotypes in S42 and S42ILs
      were utilized to determine the genetic map location of the candidate genes and to
      test if these genes may exert quantitative trait locus (QTL) effects on flowering
      time, yield and yield-related traits in the two populations studied. By
      sequencing the characteristic regions of the genes and genotyping with diagnostic
      markers, the contrasting allelic constitutions of four known flowering regulation
      genes were identified as ppd-H1, Vrn-H1, vrn-H2 and vrn-H3 in 'Scarlett' and as
      Ppd-H1, vrn-H1, Vrn-H2 and a novel allele of VRN-H3 in 'ISR42-8'. All candidate
      genes could be placed on a barley simple sequence repeat (SSR) map. Seven
      candidate genes (Ppd-H1, VRN-H2, VRN-H3, HvGI, HvFT2, HvFT3 and HvFT4) were
      associated with flowering time QTLs in population S42. Four exotic alleles (Ppd
      H1, Vrn-H2, vrn-H3 and HvCO1) possibly exhibited significant effects on flowering
      time in S42ILs. In both populations, the QTL showing the strongest effect
      corresponded to Ppd-H1. Here, the exotic allele was associated with a reduction
      of number of days until flowering by 8.0 and 12.7%, respectively. Our data
      suggest that Ppd-H1, Vrn-H2 and Vrn-H3 may also exert pleiotropic effects on
      yield and yield-related traits.

PMID- 20155246
TI  - Developing and comparing methods for measuring the content of care in mental
      health services.
AB  - BACKGROUND: Measurement of what happens in mental health services is needed to
      describe services, identify variation in care provision and understand service
      outcomes. However, there is no consensus about appropriate methods or measures
      for content of care. Previous research has primarily used a single information
      source and prioritised staff over patient perspectives on content of care. This
      study aims to enhance understanding of how to measure content of care by
      developing and evaluating four instruments, each using a different measurement
      method. METHODS: Development is described by four instruments-CaSPAR, CaRICE,
      CCCQ-S and CCCQ-P-which use researcher observation, staff-report and patient
      report to measure the intensity and nature of care at services. Inter-rater
      reliability of CaRICE and CCCQ-S was investigated. Concordance between staff and
      patient perspectives was explored through assessing inter-rater agreement of CCCQ
      S and CCCQ-P questionnaires. The convergence of data from the measures collected
      in an inpatient multi-site study was investigated. RESULTS: CaRICE demonstrated
      good inter-rater reliability (kappa = 0.71). CCCQ-S inter-rater reliability was
      poor. Concordance between staff and patient reports was low: there was a trend
      for patients to report less care received than staff reported had been provided.
      Results from CaSPAR, CaRICE and CCCQ-P exhibited divergence, indicating possible
      differences in patient, staff and researcher perspectives. DISCUSSION:
      Information about content of care should be sought as close as possible to the
      point of delivery. There may be differing, valid perspectives about care provided
      by services. Further development of methods to measure content of care is
      required. Meanwhile, a multi-methods approach should be adopted, which allows
      inclusion of different perspectives (specifically including the patient's
      perspective) and triangulation of results from different measurement methods.
      CaSPAR, CaRICE and CCCQ-P can provide multi-perspective content of care
      measurement in inpatient services.

PMID- 20155247
TI  - Effects of 25-hydroxyvitamin D level and its change on parathyroid hormone in
      premenopausal Chinese women.
AB  - Optimal levels of 25-hydroxyvitamin D [25(OH)D] were investigated in
      premenopausal Chinese women. Parathyroid hormone (PTH) change at 3 months was
      associated with change in 25(OH)D but not with baseline levels, and PTH fell even
      when starting levels of 25(OH)D were >40 nmol/L, consistent with optimal values
      for 25(OH)D of >=40 nmol/l. INTRODUCTION: The upper level of 25-hydroxyvitamin D
      [25(OH)D] which constitutes a long-term bone health risk by causing elevated PTH
      levels is uncertain. Although many studies have addressed this question using
      cross-sectional data, the present study is one of few employing a prospective
      approach to determine 25(OH)D levels required to minimize PTH. METHODS:
      Relationships among baseline values and 3-month changes (Delta) in PTH and
      25(OH)D were assessed in 221 Chinese women, aged 28.0+/-4.4 years (mean+/-SD),
      taking part in a placebo-controlled dairy product intervention delivering 200 IU
      vitamin D(3)/day. RESULTS: Baseline 25(OH)D was 34+/-11 nmol/L and was inversely
      related to baseline PTH (r=-0.18, P=0.007), with a plateau in PTH levels when
      25(OH)D was >40 nmol/L. After 3 months intervention, PTH fell 11% and neither
      Delta25(OH)D nor DeltaPTH differed between treatment and control groups. DeltaPTH
      was inversely related to Delta25(OH)D (P<0.001) but not to baseline 25(OH)D.
      Similarly, DeltaPTH differed between quartiles of Delta25(OH)D (P<0.001), but not
      between quartiles of baseline 25(OH)D and no interaction was observed between
      quartiles of baseline 25(OH)D and Delta25(OH)D. Even in the highest quartile of
      baseline 25(OH)D (>40 nmol/L), PTH fell 0.4+/-0.1 pmol/L (mean+/-SEM; P=0.008).
      CONCLUSIONS: We conclude that vitamin D deficiency is common in young women in
      Hong Kong. The cross-sectional analysis indicates that optimal 25(OH)D is >40
      nmol/L, and the longitudinal data is consistent with a higher optimal value which
      is not defined in this study's results.

PMID- 20155249
TI  - Determination of 11 priority pollutant phenols in wastewater using dispersive
      liquid-liquid microextraction followed by high-performance liquid chromatography
      diode-array detection.
AB  - Dispersive liquid-liquid microextraction coupled with high-performance liquid
      chromatography-diode-array detection was applied for the extraction and
      determination of 11 priority pollutant phenols in wastewater samples. The
      analytes were extracted from a 5-mL sample solution using a mixture of carbon
      disulfide as the extraction solvent and acetone as the dispersive solvent. After
      extraction, solvent exchange was carried out by evaporating the solvent and then
      reconstituting the residue in a mixture of methanol-water (30:70). The influences
      of different experimental dispersive liquid-liquid microextraction parameters
      such as extraction solvent type, dispersive solvent type, extraction and
      dispersive solvent volume, salt addition, and pH were studied. Under optimal
      conditions, namely pH 2, 165-microL extraction solvent volume, 2.50-mL dispersive
      solvent volume, and no salt addition, enrichment factors and limits of detection
      ranged over 30-373 and 0.01-1.3 microg/L, respectively. The relative standard
      deviation for spiked wastewater samples at 10 microg/L of each phenol ranged
      between 4.3 and 19.3% (n = 5). The relative recovery for wastewater samples at a
      spiked level of 10 microg/L varied from 65.5 to 108.3%.

PMID- 20155250
TI  - New approach to optimize HPLC separations of acid-base compounds with elution
      order involved, by using combined three-band resolution maps.
AB  - Some of the optimization methods in reversed phase high-performance liquid
      chromatography (RP-HPLC) are based on resolution of the critical band pair.
      Mobile phase composition is changed systematically to establish those conditions
      giving an acceptable resolution for such a critical band pair, but sometimes the
      critical pair may change with the separation conditions, which obliges to
      identify it for each of those conditions. In the case of ionizable compounds,
      more than two bands may be involved in resolution, showing--in some cases-
      changes in the elution order when the mobile phase composition was modified. In
      this paper, an alternative way that does not identify the critical pair after
      changing experimental conditions is proposed. The relative separation of the
      three bands involved in two alternating critical band pairs is evaluated as a
      sort of conjugate or combined resolution, represented as contour maps vs. two
      variables (content of organic modifier and pH). These maps are obtained from data
      of chromatograms made under different separation conditions; these conditions
      were generated by experimental design and data was mathematically processed with
      a computer program. Analytes of three families that have acid-base properties,
      triazines, phenoxyacids, and phenols, were used for this purpose. The
      chromatographic behavior when elution order reversion of ionizable compounds
      exists is studied.

PMID- 20155251
TI  - Hot embossing of electrophoresis microchannels in PMMA substrates using electric
      heating wires.
AB  - A simple method based on electric heating wires has been developed for the rapid
      fabrication of poly(methyl methacrylate) (PMMA) electrophoresis microchips in
      ordinary laboratories without the need for microfabrication facilities. A piece
      of stretched electric heating wire placed across the length of a PMMA plate along
      its midline was sandwiched between two microscope slides under pressure.
      Subsequently, alternating current was allowed to pass through the wire to
      generate heat to emboss a separation microchannel on the PMMA separation channel
      plate at room temperature. The injection channel was fabricated using the same
      procedure on a PMMA sheet that was perpendicular to the separation channel. The
      complete microchip was obtained by bonding the separation channel plate to the
      injection channel sheet, sealing the channels inside. The electric heating wires
      used in this work not only generated heat; they also served as templates for
      embossing the microchannels. The prepared microfluidic microchips have been
      successfully employed in the electrophoresis separation and detection of ions in
      connection with contactless conductivity detection.

PMID- 20155252
TI  - Sensitive headspace gas chromatography analysis of free and conjugated 1-methoxy
      2-propanol in urine.
AB  - Glycol ethers still continue to be a workplace hazard due to their important use
      on an industrial scale. Currently, chronic occupational exposures to low levels
      of xenobiotics become increasingly relevant. Thus, sensitive analytical methods
      for detecting biomarkers of exposure are of interest in the field of occupational
      exposure assessment. 1-Methoxy-2-propanol (1M2P) is one of the dominant glycol
      ethers and the unmetabolized urinary fraction has been identified to be a good
      biological indicator of exposure. An existing analytical method including a solid
      phase extraction and derivatization before GC/FID analysis is available but
      presents some disadvantages. We present here an alternative method for the
      determination of urinary 1M2P based on the headspace gas chromatography
      technique. We determined the 1M2P values by the direct headspace method for 47
      samples that had previously been assayed by the solid-phase extraction and
      derivatization gas chromatography procedure. An inter-method comparison based on
      a Bland-Altman analysis showed that both techniques can be used interchangeably.
      The alternative method showed a tenfold lower limit of detection (0.1 mg/L) as
      well as good accuracy and precision which were determined by several urinary 1M2P
      analyses carried out on a series of urine samples obtained from a human volunteer
      study. The within- and between-run precisions were generally about 10%, which
      corresponds to the usual injection variability. We observed that the differences
      between the results obtained with both methods are not clinically relevant in
      comparison to the current biological exposure index of urinary 1M2P. Accordingly,
      the headspace gas chromatography technique turned out to be a more sensitive,
      accurate, and simple method for the determination of urinary 1M2P.

PMID- 20155254
TI  - Oxidative protein labeling in mass-spectrometry-based proteomics.
AB  - Oxidation of proteins and peptides is a common phenomenon, and can be employed as
      a labeling technique for mass-spectrometry-based proteomics. Nonspecific
      oxidative labeling methods can modify almost any amino acid residue in a protein
      or only surface-exposed regions. Specific agents may label reactive functional
      groups in amino acids, primarily cysteine, methionine, tyrosine, and tryptophan.
      Nonspecific radical intermediates (reactive oxygen, nitrogen, or halogen species)
      can be produced by chemical, photochemical, electrochemical, or enzymatic
      methods. More targeted oxidation can be achieved by chemical reagents but also by
      direct electrochemical oxidation, which opens the way to instrumental labeling
      methods. Oxidative labeling of amino acids in the context of liquid
      chromatography(LC)-mass spectrometry (MS) based proteomics allows for
      differential LC separation, improved MS ionization, and label-specific
      fragmentation and detection. Oxidation of proteins can create new reactive groups
      which are useful for secondary, more conventional derivatization reactions with,
      e.g., fluorescent labels. This review summarizes reactions of oxidizing agents
      with peptides and proteins, the corresponding methodologies and instrumentation,
      and the major, innovative applications of oxidative protein labeling described in
      selected literature from the last decade.

PMID- 20155256
TI  - In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the
      Serbian population.
AB  - PURPOSE: The main aim of the study was to investigate the distribution of
      cytochrome P450 2A6 (CYP2A6) and xanthine oxidase (XO) enzyme activities in the
      Serbian population. Secondly, we tested the influence of genetics (CYP2A6
      polymorphism), sex, and cigarette smoking on both enzymes. METHODS: One hundred
      forty healthy Serbian volunteers were genotyped for common CYP2A6 alleles. In 100
      of them, CYP2A6 and XO activities were determined by the urinary 17U/17X and
      1U/(1U + 1X) ratios, respectively, after oral administration of 100 mg caffeine
      as a probe. RESULTS: A 21-fold variation in the 17U/17X ratio was observed
      (range: 0.49-10.28, mean = 1.65, 95% CI: 1.49-1.83). The urinary 1U/(1U + 1X)
      ratios displayed four-fold variation, ranging from 0.17 to 0.71 (mean = 0.43, 95%
      CI: 0.41-0.45). CYP2A6 alleles *1A, *1B1, *9, *4 and *1B1x2 were found with
      frequencies of 0.579, 0.307, 0.082, 0.029, and 0.004 respectively. CYP2A6*5 was
      not detected. CYP2A6 genotype influenced interindividual variability in CYP2A6
      enzyme activity (P = 0.04). Cigarette smoking inhibited CYP2A6 enzyme activity (P
      = 0.02), but had no effect on activity of XO (P = 0.16).There was no significant
      difference between men and women in terms of CYP2A6 or XO activity. CONCLUSIONS:
      Serbs displayed interindividual variations in CYP2A6 activity. CYP2A6 genotype
      and cigarette smoking, but not sex, influenced CYP2A6 enzyme activity. Unimodal
      distribution of XO enzyme activity in Serbs implies the absence of subjects with
      low enzyme activity in this population. XO activity is not influenced by sex or
      cigarette smoking.

PMID- 20155258
TI  - Noncompaction of the right ventricle.

PMID- 20155260
TI  - Perinatal clinical and imaging features of CLOVES syndrome.
AB  - We report a neonate with antenatal imaging features suggestive of CLOVES
      syndrome. Postnatal clinical and imaging findings confirmed the diagnosis, with
      the constellation of truncal overgrowth, cutaneous capillary malformation,
      lymphatic and musculoskeletal anomalies. The clinical, radiological and
      histopathological findings noted in this particular phenotype help differentiate
      it from other overgrowth syndromes with complex vascular anomalies.

PMID- 20155259
TI  - Giant aneurysms associated with aortic coarctation: management challenges and
      options.
AB  - The management of giant aneurysms associated with aortic coarctation is
      challenging. The location, the size of the aneurysm, whether it has ruptured,
      previous coarctation repair, the presence of stenosis, and the ascending and
      distal aortic pathology will all influence the treatment approach. With more
      patients surviving to adulthood after early coarctation repair, a better
      understanding of the anatomy, pathophysiology, and radiological findings of
      coarctation-related aneurysms is imperative to providing sound care. We present
      here our experience with a series of giant aneurysms of the aorta, all with a
      background of underlying aortic coarctation. We highlight the decision-making
      process and review current management trends.

PMID- 20155257
TI  - Novel strategies for the treatment of inflammatory hyperalgesia.
AB  - There is a large unmet medical need in the area of treatment of inflammatory pain
      initiated by tissue damage or inflammation that manifests as spontaneous pain and
      pain hypersensitivity (hyperalgesia).The current review focuses on the key
      mechanisms that produce hyperalgesia that accompanies inflammation. Also, the
      inflammatory mediators that interact with neurons to produce hyperalgesia are
      explored. As the dominant classes of analgesic drugs such as the NSAIDs and the
      opiates are limited by their side effects and tolerability, elucidation of the
      molecular mechanisms responsible for inflammatory pain provides novel
      opportunities for therapeutic approaches for managing inflammatory pain, with
      improved specificity, efficacy, and possibly with fewer toxic effects.

PMID- 20155261
TI  - Torsed pulmonary sequestration presenting as a painful chest mass.
AB  - Pulmonary sequestration is a congenital abnormality that can be divided into
      intralobar or extralobar types. Both types are characterized by pulmonary tissue
      that does not communicate with the bronchial tree or pulmonary arteries and
      typically has its arterial supply arising from the descending aorta. We report a
      case of an 11-year-old girl with extralobar sequestration who presented with
      torsion causing abdominal pain and pleuritic chest pain.

PMID- 20155262
TI  - Nasal epidermoid cyst with sinus tract.

PMID- 20155263
TI  - PET imaging of HER1-expressing xenografts in mice with 86Y-CHX-A''-DTPA
      cetuximab.
AB  - PURPOSE: Cetuximab is a recombinant, human/mouse chimeric IgG(1) monoclonal
      antibody that binds to the epidermal growth factor receptor (EGFR/HER1).
      Cetuximab is approved for the treatment of patients with HER1-expressing
      metastatic colorectal cancer. Limitations in currently reported radiolabeled
      cetuximab for PET applications prompted the development of (86)Y-CHX-A''-DTPA
      cetuximab as an alternative for imaging HER1-expressing cancer. (86)Y-CHX-A''
      DTPA-cetuximab can also serve as a surrogate marker for (90)Y therapy. METHODS:
      Bifunctional chelate, CHX-A''-DTPA was conjugated to cetuximab and radiolabeled
      with (86)Y. In vitro immunoreactivity was assessed in HER1-expressing A431 cells.
      In vivo biodistribution, PET imaging and noncompartmental pharmacokinetics were
      performed in mice bearing HER1-expressing human colorectal (LS-174T and HT29),
      prostate (PC-3 and DU145), ovarian (SKOV3) and pancreatic (SHAW) tumor
      xenografts. Receptor blockage was demonstrated by coinjection of either 0.1 or
      0.2 mg cetuximab. RESULTS: (86)Y-CHX-A''-DTPA-cetuximab was routinely prepared
      with a specific activity of 1.5-2 GBq/mg and in vitro cell-binding in the range
      65-75%. Biodistribution and PET imaging studies demonstrated high HER1-specific
      tumor uptake of the radiotracer and clearance from nonspecific organs. In LS-174T
      tumor-bearing mice injected with (86)Y-CHX-A''-DTPA-cetuximab alone, (86)Y-CHX
      A''-DTPA-cetuximab plus 0.1 mg cetuximab or 0.2 mg cetuximab, the tumor uptake
      values at 3 days were 29.3 +/- 4.2, 10.4 +/- 0.5 and 6.4 +/- 0.3%ID/g,
      respectively, demonstrating dose-dependent blockage of the target. Tumors were
      clearly visualized 1 day after injecting 3.8-4.0 MBq (86)Y-CHX-A''-DTPA
      cetuximab. Quantitative PET revealed the highest tumor uptake in LS-174T (29.55
      +/- 2.67%ID/cm(3)) and the lowest tumor uptake in PC-3 (15.92 +/- 1.55%ID/cm(3))
      xenografts at 3 days after injection. Tumor uptake values quantified by PET were
      closely correlated (r (2) = 0.9, n = 18) with values determined by
      biodistribution studies. CONCLUSION: This study demonstrated the feasibility of
      preparation of high specific activity (86)Y-CHX-A''-DTPA-cetuximab and its
      application for quantitative noninvasive PET imaging of HER1-expressing tumors.
      (86)Y-CHX-A''-DTPA-cetuximab offers an attractive alternative to previously
      labeled cetuximab for PET and further investigation for clinical translation is
      warranted.

PMID- 20155265
TI  - Moving from lymph node metastasis in gastric cancer to biological markers: reply
      to letter.

PMID- 20155264
TI  - Transcatheter arterial embolization for hemoperitoneum: unusual manifestation of
      iatrogenic injury to abdominal muscular arteries.
AB  - PURPOSE: To evaluate the etiology of unusual manifestation of hemoperitoneum and
      the efficacy of transcatheter arterial embolization (TAE). MATERIALS AND METHODS:
      A retrospective review of patients at three hospitals was performed. A total of
      12 patients (M:F = 5:7, mean age: 48) had massive hemoperitoneum without evidence
      of an intramuscular hematoma on CT (n = 10) or US (n = 2) after injury to the
      abdominal wall. The patients underwent TAE. The etiology of iatrogenic injury to
      the abdominal muscular arteries and the effectiveness of embolization were
      evaluated. RESULTS: Among 12 patients, 11 patients had injuries to the inferior
      epigastric artery (IEA) and one patient had an injury to the deep circumflex
      iliac artery (DCIA). The causes of the injuries were: paracentesis (n = 6), open
      laparotomy (n = 4), removal of a CAPD catheter (n = 1), and surgical drain (n =
      1). The TAE was successfully performed in all patients. Over 10 days of follow-up
      after the embolization, all patients were stabilized hemodynamically. CONCLUSION:
      Injury to the IEA or DCIA should be considered as a possible source of
      hemoperitoneum even in patients with no evidence of an intramuscular hematoma
      after injury to the superficial arteries of the abdominal wall. In addition, such
      injuries can be treated successfully using TAE.

PMID- 20155266
TI  - Traumatic subcapsular splenic hematoma revealing littoral cell angioma and
      Gaucher's disease.

PMID- 20155267
TI  - Assessment of immunogenicity of romiplostim in clinical studies with ITP
      subjects.
AB  - Romiplostim is an Fc-peptide fusion protein that activates intracellular
      transcriptional pathways via the thrombopoietin (TPO) receptor leading to
      increased platelet production. Romiplostim has been engineered to have no amino
      acid sequence homology to endogenous TPO. Recombinant protein therapeutics can be
      at a risk of development of an antibody response that can impact efficacy and
      safety. Hence, a strategy to detect potential antibody formation to the drug and
      to related endogenous molecules can be useful. The immunogenicity assessment
      strategy involved both the detection and characterization of binding and
      neutralizing antibodies. The method for detection was based on a surface plasmon
      resonance biosensor platform using the Biacore 3000. Samples that tested positive
      for binding antibodies in the Biacore immunoassay were then tested in a
      neutralization assay. Serum samples from 225 subjects with immune
      thrombocytopenic purpura (ITP) dosed with romiplostim and 45 ITP subjects dosed
      with placebo were tested for romiplostim and TPO antibodies. Prior to romiplostim
      treatment, 17 subjects (7%) tested romiplostim antibody positive and 12 subjects
      (5%) tested TPO antibody positive for pre-existing binding antibodies. After
      romiplostim exposure, 11% of the subjects exhibited binding antibodies against
      romiplostim and 5% of the subjects with ITP showed binding antibodies against
      TPO. The antibodies against romiplostim did not cross-react with TPO and vice
      versa. No cases of anti-TPO neutralizing antibodies were detected in romiplostim
      treated subjects. The incidence of anti-romiplostim neutralizing antibodies to
      romiplostim was 0.4% (one subject); this subject tested negative at the time of
      follow-up 4 months later. No impact on platelet profiles were apparent in
      subjects that had antibodies to romiplostim to date. In summary, administration
      of romiplostim in ITP subjects resulted in the development of a binding antibody
      response against romiplostim and TPO ligand. One subject developed a neutralizing
      antibody response to romiplostim that impacted the platelet counts of this
      subject. No neutralizing antibodies to endogenous TPO were observed.

PMID- 20155268
TI  - Hyper-alkalinization without hyper-hydration for the prevention of high-dose
      methotrexate acute nephrotoxicity in patients with osteosarcoma.
AB  - PURPOSE: To evaluate the reliability and renal safety of an original schedule of
      high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and
      without hyper-hydration. METHODS: Patients with osteosarcoma received HDMTX (8-12
      g/m(2)) as a 4-h infusion. Hypertonic 8.4% sodium bicarbonate was infused prior
      to HDMTX, then once daily for 3 days. Methotrexate serum concentrations were
      measured at hour 4 (Cmax), hour 24, hour 48, and hour 72. Urinary pH was measured
      on each miction. Serum creatinine was assessed on days 1, 3, and 8. RESULTS:
      Twenty-six patients (median age: 18 years, range: 15-25) received a total of 344
      cycles of HDMTX, including 16 patients treated in an outpatient basis. Urinary pH
      remained constantly higher than 7.5 in all patients. Grade 1 creatininemia
      toxicity was observed in 31 cycles (9%), and grade 2 creatinine toxicity was
      observed in one patient. No episode of acute severe nephrotoxicity was observed.
      No significant worsening was observed in serum creatinine and calculated
      creatinine clearance from baseline to the end of therapy (P = 0.74). The main
      extra-renal toxicity was alkalinization-related hypokalemia from H48. No re
      hospitalization was required. CONCLUSION: Hyper-alkalinization appears an
      efficient and reliable method to prevent the acute renal toxicity of HDMTX and
      allows its safe administration in the outpatient setting.

PMID- 20155269
TI  - The remodeling of collagen fibers in rats ankles submitted to immobilization and
      muscle stretch protocol.
AB  - To evaluate the remodeling of collagen fibers in the articular cartilage of rat
      ankles, with and without immobilization, after application of muscle stretching
      protocol. Twenty three Wistar rats were divided into four groups: immobilized
      (I), n=6; immobilized and stretched (IS), n=6; stretched (S), n=6 and control
      (C), n=5. The animals in groups I and IS were submitted to immobilization. After
      the period of immobilization, the animals in groups IS and S were submitted to a
      muscle stretching protocol. At the end of the experiment, the animals were
      euthanized and the joints removed, processed and stained with Picrosirius red.
      The analysis was carried out using a polarized light microscope. The density of
      collagen fibers were quantified according to the intensity of birefringence
      displayed. By way of statistical analyses, the right and left hind limbs of the
      different groups were compared based on the total density of collagen fibers, the
      density of thick collagen fibers and the density of thin collagen fibers.
      Immobilization promoted a reduction in density of the thin fibers and of total
      collagen. The muscle stretching protocol after immobilization promoted a
      reduction in density of the total collagen and of the thick fibers, but the
      density of the thin fibers showed the same values as control. The collagen fibers
      were remodeled by the different stimuli. Immobilization was harmful to the
      collagen fibers and the muscle stretching protocol only recovered the thin
      collagen fibers.

PMID- 20155271
TI  - No news from Norway.

PMID- 20155270
TI  - Prevalence of first-pass myocardial perfusion defects detected by contrast
      enhanced dual-source CT in patients with non-ST segment elevation acute coronary
      syndromes.
AB  - OBJECTIVE: To investigate the prevalence and diagnostic value of first-pass
      myocardial perfusion defects (PD) visualised by contrast-enhanced multidetector
      computed tomography (MDCT) in patients admitted for a first acute coronary
      syndrome (ACS). METHODS: Thirty-eight patients with non-ST segment elevation
      myocardial infarction (NSTEMI) or unstable angina (UA) and scheduled for
      percutaneous coronary intervention underwent dual-source CT immediately before
      catheterisation. CT images were analysed for the presence of any PD by using a 17
      segment model. Results were compared with peak cardiac troponin-I (cTnI) and
      angiography findings. RESULTS: PD were seen in 21 of the 24 patients with NSTEMI
      (median peak cTnI level 7.07 ng/mL; range 0.72-37.07 ng/mL) and in 2 of 14
      patients with UA. PD corresponded with the territory of the infarct-related
      artery in 20 out of 22 patients. In a patient-based analysis, sensitivity,
      specificity, negative and positive predictive values of any PD for predicting
      NSTEMI were 88%, 86%, 80% and 91%. Per culprit artery, the respective values were
      86%, 75%, 80% and 83%. CONCLUSION: In patients with non-ST segment elevation ACS,
      first-pass myocardial PD in contrast-enhanced MDCT correlate closely with the
      presence of myocardial necrosis, as determined by increases in cTnI levels.

PMID- 20155272
TI  - Pulmonary talcosis: imaging findings.
AB  - Talc is a mineral widely used in the ceramic, paper, plastics, rubber, paint, and
      cosmetic industries. Four distinct forms of pulmonary disease caused by talc have
      been defined. Three of them (talcosilicosis, talcoasbestosis, and pure talcosis)
      are associated with aspiration and differ in the composition of the inhaled
      substance. The fourth form, a result of intravenous administration of talc, is
      seen in drug users who inject medications intended for oral use. The disease most
      commonly affects men, with a mean age in the fourth decade of life. Presentation
      of patients with talc granulomatosis can range from asymptomatic to fulminant
      disease. Symptomatic patients typically present with nonspecific complaints,
      including progressive exertional dyspnea, and cough. Late complications include
      chronic respiratory failure, emphysema, pulmonary arterial hypertension, and cor
      pulmonale. History of occupational exposure or of drug addiction is the major
      clue to the diagnosis. The high-resolution computed tomography (HRCT) finding of
      small centrilobular nodules associated with heterogeneous conglomerate masses
      containing high-density amorphous areas, with or without panlobular emphysema in
      the lower lobes, is highly suggestive of pulmonary talcosis. The characteristic
      histopathologic feature in talc pneumoconiosis is the striking appearance of
      birefringent, needle-shaped particles of talc seen within the giant cells and in
      the areas of pulmonary fibrosis with the use of polarized light. In conclusion,
      computed tomography can play an important role in the diagnosis of pulmonary
      talcosis, since suggestive patterns may be observed. The presence of these
      patterns in drug abusers or in patients with an occupational history of exposure
      to talc is highly suggestive of pulmonary talcosis.

PMID- 20155273
TI  - Crocidolite induces prostaglandin I(2) release mediated by vitronectin receptor
      and cyclooxygenase-2 in lung cells.
AB  - Interstitial lung disease (ILD) produces disruption of alveolar walls with loss
      of functionality and scar tissue accumulation. Asbestosis is the ILD produced by
      the inhalation of asbestos fibers. This study attempts to elucidate the role of
      lung epithelial cells in the generation of asbestos-induced ILD. When exposed to
      crocidolite LA-4 cells had a decrease in viability and an increase in the release
      of lactate dehydrogenase (LDH) and 6-keto PGF(1alpha), a PGI(2) metabolite.
      PGI(2) release was mediated by cyclooxygenase-2 (COX-2) and vitronectin receptor
      (VNR). When LA-4 cells were treated with VNR inhibitors, either RGD (Arg-Gly-Asp)
      peptide or VNR blocking antibody, a statistically significant decrease in PGI(2)
      metabolite production was observed, but crocidolite-induced cytotoxicity was not
      prevented. These findings propose that crocidolite is coated by an RGD protein
      and binds VNR-inducing COX-2 expression and PGI(2) release. Moreover, when LA-4
      cells were exposed to crocidolite in the presence of reduced serum culture media,
      PGI(2) production was prevented, and when bronchoalveolar lavage fluid (BALF) was
      added, PGI(2) production was rescued. Cytotoxicity did not occur, either in
      reduced serum culture media or when BALF was added. In conclusion, crocidolite
      requires the presence of an RGD protein coating the fibers to induce inflammation
      (PGI(2) production) and crocidolite alone cannot induce cytotoxicity in lung
      cells.

PMID- 20155274
TI  - Transitory somatoparaphrenia associated with a left frontoparietal meningioma.

PMID- 20155275
TI  - Lateralization of cerebral blood flow in juvenile absence seizures.
AB  - Cerebrovascular blood flow in absence seizures and flow patterns during the ictal
      period have not been thoroughly investigated. We aimed to evaluate cerebral blood
      flow changes in typical juvenile absence seizures during the ictal and postictal
      phases. Seizures were recorded in three patients (mean age: 21 +/- 1 years) with
      multiple daily typical absence seizures. Simultaneous video
      electroencephalography and bilateral middle cerebral artery transcranial Doppler
      ultrasonography recordings were conducted during seizures. Basal, ictal, and
      postictal blood flow velocities were recorded bilaterally, and offline analyses
      were performed in relation with generalized spike and wave discharges. Total of
      43 seizures were recorded. Ictal increase and postictal decrease of cerebral
      blood flow velocities were significant for both sides (P < 0.001). The
      interhemispheric asymmetry in the ictal velocity increase was significant (P <
      0.05). The interhemispheric asymmetry in the postictal velocity decrease was not
      significant (P > 0.05). The blood flow velocity increase after seizure onset
      indicates a vascular coupling mechanism. A sudden and then a gradual decrease in
      blood flow velocity, which lasted even after the seizure ceased, might suggest a
      preventive mechanism to avoid excessive seizure duration or even an absence
      status epilepticus. Significant asymmetries in increase and a symmetrical
      decrease may support the cortical focus theory.

PMID- 20155276
TI  - Trigeminal herpes zoster and Ramsay Hunt syndrome with a lesion in the spinal
      trigeminal nucleus and tract.
AB  - We report the case of a 77-year-old immuno-competent man who developed herpes
      zoster in the maxillary and mandibular branches of the trigeminal nerve. Within 3
      weeks, he developed ipsilateral peripheral facial palsy, hearing loss, vesicles
      over the external auditory canal, and pain in the face and ear. A T(2)-weighted
      MRI of the brain revealed a hyper-intense lesion at the right medulla
      corresponding to the spinal trigeminal nucleus and tract. Gadolinium enhancement
      was seen over the right facial nerve. These lesions suggest a possibility of
      transaxonal spread of the varicella zoster virus between the trigeminal nerve,
      the facial nerve, and the spinal trigeminal nucleus and tract.

PMID- 20155277
TI  - Association of restless legs syndrome, chronic motor tic disorder and migraine
      with aura: a case of a single family.

PMID- 20155279
TI  - Chorioretinectomy for perforating or severe intraocular foreign body injuries.
AB  - BACKGROUND: To report the outcomes of chorioretinectomy versus non
      chorioretinectomy in combat ocular injuries where a foreign body penetrated the
      choroid or perforated the globe. METHODS: Retrospective, comparative, consecutive
      interventional case series of 32 perforating or severe intraocular foreign body
      combat ocular trauma injuries sustained by United States military soldiers and
      treated at a single institution from March 2003 to March 2009. Final best
      corrected visual acuity (BCVA) in 19 non-chorioretinectomy-treated eyes was
      compared to 13 chorioretinectomy-treated eyes. The chorioretinectomy group was
      repaired with a 20 gauge three-port pars plana vitrectomy (PPV) by removing the
      choroid and/or retina at the impact or perforation site of the foreign body
      following evacuation from a combat zone. The main outcome measures were best
      corrected visual acuity and rates of globe survival, retina reattachment and
      proliferative vitreoretinopathy. RESULTS: Thirty-two eyes of 31 patients with a
      mean age of 29 +/- 9 years (range, 19-53 years) were followed for a median of 463
      +/- 226 days (range, 59-1022 days). The mean time of injury to the operating room
      in the chorioretinectomy group was 12.6 +/- 9.8 days, compared to that of the non
      chorioretinectomy group of 22.1 +/- 16.4 days (P = 0.05) Final BCVA > or =20/200
      occurred in seven of 13 (54%) of the chorioretinectomy group, compared to two of
      19 (11%) in the non-chorioretinectomy group (P = 0.04). Globe survival rates were
      higher in the chorioretinectomy group [11 of 13 (85%) vs 9 of 19 (45%); P =
      0.06], as well as the final retinal reattachment rate [8 of 13 (62%) vs 8 of 19
      (42%); P = 0.47]. The proliferative vitreoretinopathy rate was eight of 13 (62%)
      in the chorioretinectomy group, compared to 14 of 19 (74%) in the non
      chorioretinectomy group (P = 0.70). Graft failure occurred in five of six eyes
      (83%) of non-chorioretinectomy cases, requiring temporary keratoprosthesis and
      penetrating keratoplasty. CONCLUSION: Chorioretinectomy is a surgical option that
      may improve final BCVA and increase globe survival rates when a foreign body
      penetrates the choroid or perforates the globe.

PMID- 20155280
TI  - Peripheral nerve sheath tumors of the gastrointestinal tract: a multicenter study
      of 58 patients including NF1-associated gastric schwannoma and unusual
      morphologic variants.
AB  - The frequency and morphological spectrum of gastrointestinal peripheral nerve
      sheath tumors (PNSTs) from consecutive case material has not been studied in the
      c-KIT era. We reviewed all mesenchymal gastrointestinal (GI) lesions at our
      departments according to current diagnostic criteria. PNSTs formed the third
      commonest group of mesenchymal GI tumors with a lower frequency (< or =5%)
      compared to gastrointestinal stromal tumors (GISTs; approximately 50%) and smooth
      muscle neoplasms ( approximately 30%). Granular cell tumors (GCTs; n = 31) and
      schwannomas (n = 22) were the most common types of PNSTs encountered. Rare tumors
      included neurofibromatosis 1 (NF1)-associated PNSTs (n = 5) and gastric
      perineurioma (n = 1). Thirteen schwannomas (including also some recent cases)
      were initially diagnosed as GIST, leiomyoma, or neurofibroma. Unusual
      histological variants included sigmoid GCT with prominent lipomatous component (n
      = 1), reticular-microcystic schwannoma of small (n = 1) and large (n = 1) bowel,
      NF1-associated gastric schwannoma (the first case to date), and psammomatous
      melanotic colonic schwannoma unrelated to Carney complex (n = 1). PNSTs coexisted
      with GIST in four patients (three had definite NF1). In conclusion, PNSTs of the
      GI tract are rare uniformly benign neoplasms that may show schwannian,
      perineurial, fibroblastic, or mixed differentiation. Most of them (92%) occurred
      sporadically unassociated with NF1 or NF2. Gastrointestinal PNSTs are still
      underrecognized by general pathologists. Awareness of their diverse morphology
      will help to avoid confusing them with smooth muscle neoplasms and GIST that they
      may closely mimic.

PMID- 20155281
TI  - Immunohistochemical detection of steroid receptor cofactors in ovarian
      endometriosis: involvement of down-regulated SRC-1 expression in the limited
      growth activity of the endometriotic epithelium.
AB  - To study the steroid hormone-induced growth mechanisms of endometriosis, the
      immunohistochemical expression of steroid hormone receptor cofactors was
      investigated in 37 cases of endometriotic epithelia and was compared with that of
      eutopic endometria of identical patients. The expression of steroid receptor
      coactivators (p300/CBP and SRC-1) and corepressors (NCoR and SMRT) was examined
      in relation to the estrogen receptor (ER), the progesterone receptor (PR), and Ki
      67. Results of immunostaining were indicated as a "positivity index" (PI, full
      score; 100). The expression of ER and PR in endometriotic epithelia largely
      resembled that in eutopic endometria, however, the expression of Ki-67 in the
      proliferative phase (PI 13.8 +/- 2.4, mean +/- SD) was significantly lower than
      that in eutopic endometria (32.6 +/- 10.6). The expression of SRC-1 in eutopic
      endometria was increased in the proliferative phase (56.5 +/- 16.8) and decreased
      in the secretory phase (14.8 +/- 6.9). In endometriosis, however, the PI for SRC
      1 did not show apparent cyclic changes during the menstrual cycle. Moreover, the
      expression of SRC-1 in endometriotic epithelia in the proliferative phase was
      significantly lower than that in eutopic endometria. These findings suggested the
      reduced proliferative activity in endometriotic epithelia to be related to the
      reduced expression of SRC-1.

PMID- 20155283
TI  - RETRACTED ARTICLE: 67-kDa laminin receptor induces FasL expression and FasL
      mediated apoptosis through the activation of c-Myc and the subsequent activation
      of the FasL promoter in human cholangiocarcinoma cells.

PMID- 20155282
TI  - Striking LD50 variation associated with fluctuations of CYP2E1-positive cells in
      hepatic lobule during chronic CCl4 exposure in mice.
AB  - Intraperitoneal injection of serially diluted carbon tetrachloride (CCl(4)) from
      0.2 to 2.0 ml/kg produced an LD(50) value of 0.46 ml/kg in the normal mouse.
      Following repeated administration of 0.2 ml/kg CCl(4) twice a week for 1 and 3
      months, the LD(50) values were over 2.0 and 0.72 ml/kg, respectively. A single
      administration of 0.2 ml/kg CCl(4) induced, within 24 h, apoptotic death of liver
      cells in the centrilobular zone 3 that were observed positive in cytochrome P450
      2E1 (CYP2E1). However, after repeated exposure to 0.2 ml/kg twice a week for 1
      month, cells in the centrilobular area were almost completely replaced with
      CYP2E1-negative cells. These cells were tolerant to CCl(4). After 3 months of
      exposure, a considerable number of CYP2E1-positive hepatocytes were observed
      throughout the periportal zone 1 and intermediate zone 2. Thus, fluctuations in
      CYP2E1-positive cells during chronic exposure to low doses of CCl(4) induced
      tolerance, which can be partially lost after prolonged CCl(4) exposure.

PMID- 20155284
TI  - The effect of bevacizumab on serum soluble FAS/FASL and TRAIL and its receptors
      (DR4 and DR5) in metastatic colorectal cancer.
AB  - PURPOSE: Bevacizumab-based chemotherapy has become the standard of care in
      metastatic colorectal cancer (MCRC). We aimed to measure the levels of serum
      soluble FAS, FASL, tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL), and its death receptors DR4 and DR5 in MCRC patients and to define
      prognostic significance of these parameters in response to bevacizumab in these
      patients. PATIENTS AND METHODS: The levels of these parameters in serum samples
      were quantified by a commercially available ELISA kit in 31 MCRC patients before
      and after 2 cycles of therapy and 25 healthy controls. RESULTS: Pretreatment sFAS
      levels in MCRC patients was significantly lower than the levels of controls (p =
      0.043). There was no significant difference in sFAS and sFASL levels in MCRC
      patients before and after bevacizumab-based treatment. There was no significant
      difference in sFAS/sFASL ratio in MCRC patients before and after treatment and
      controls. Soluble DR5 levels were significantly higher in pretreatment serum
      samples compared with controls (p = 0.008). However, pretreatment sTRAIL and sDR4
      levels were similar to the levels of controls. There was no significant
      difference in sTRAIL, sDR4, and sDR5 levels in MCRC patients before and after
      treatment. When patients were grouped according to treatment response (responders
      vs. non-responders), post-treatment sFAS/sFASL ratio was significantly lower in
      responding patients compared with non-responders (p = 0.029). Significant
      correlations were observed between post-treatment sFASL and sDR4, sFAS and
      sTRAIL, sTRAIL and sFAS/sFASL ratio, and sFASL and sDR5. CONCLUSION: Non
      significant changes in apoptotic markers with bevacizumab-based chemotherapy
      showed that they have no prognostic significance in MCRC patients. Significant
      change in sFAS/sFASL ratio according to treatment response could be an indicator
      of chemosensitivity.

PMID- 20155286
TI  - Carbon stable isotopic composition of soluble sugars in Tillandsia epiphytes
      varies in response to shifts in habitat.
AB  - We studied C stable isotopic composition (delta(13)C) of bulk leaf tissue and
      extracted sugars of four epiphytic Tillandsia species to investigate flexibility
      in the use of crassulacean acid metabolism (CAM) and C(3) photosynthetic
      pathways. Plants growing in two seasonally dry tropical forest reserves in Mexico
      that differ in annual precipitation were measured during wet and dry seasons, and
      among secondary, mature, and wetland forest types within each site. Dry season
      sugars were more enriched in (13)C than wet season sugars, but there was no
      seasonal difference in bulk tissues. Bulk tissue delta(13)C differed by species
      and by forest type, with values from open-canopied wetlands more enriched in
      (13)C than mature or secondary forest types. The shifts within forest habitat
      were related to temporal and spatial changes in vapor pressure deficits (VPD).
      Modeling results estimate a possible 4% increase in the proportional contribution
      of the C(3) pathway during the wet season, emphasizing that any seasonal or
      habitat-mediated variation in photosynthetic pathway appears to be quite moderate
      and within the range of isotopic effects caused by variation in stomatal
      conductance during assimilation through the C(3) pathway and environmental
      variation in VPD. C isotopic analysis of sugars together with bulk leaf tissue
      offers a useful approach for incorporating short- and long-term measurements of C
      isotope discrimination during photosynthesis.

PMID- 20155287
TI  - Interactive effects of elevated carbon dioxide and environmental stresses on root
      mass fraction in plants: a meta-analytical synthesis using pairwise techniques.
AB  - Rising atmospheric CO(2) greatly enhances plant production, but its effect on
      biomass allocation, particularly in the presence of environmental stresses, is
      not well understood. Here, we used meta-analysis combined with pairwise
      techniques to examine root mass fraction (RMF; i.e., the fraction of root to
      total biomass) as affected by elevated CO(2) and environmental stresses. Our
      results showed that lower soil fertility increased RMF and the magnitude was
      similar for ambient and elevated CO(2)-grown plants. Lower soil water also
      increased RMF, but to a greater extent at elevated than at ambient CO(2). While
      CO(2) enrichment had little effect on the magnitude of O(3)-caused reduction in
      RMF in herbaceous species, it alleviated the adverse effect of higher O(3) on
      root production in woody species. These results demonstrate that CO(2) has less
      pronounced effects on RMF than other environmental factors. Under abiotic
      stresses, e.g., drought and higher O(3), elevated CO(2)-grown plants will likely
      increase biomass allocation below-ground. Because of the non-uniform changes in
      drought and O(3) projected for different parts of the world, we conclude that
      elevated CO(2) will have regional, but not global, effects on biomass allocation
      under various global change scenarios.

PMID- 20155288
TI  - Delayed response in a plant-pollinator system to experimental grassland
      fragmentation.
AB  - The fragmentation of natural habitat is considered to be a major threat to
      biodiversity. Decreasing habitat quality and quantity caused by fragmentation may
      lead to a disruption of plant-pollinator interactions and to a reduction in
      sexual reproduction in plant species. We conducted a 6-year field experiment to
      investigate the effects of small-scale fragmentation on plant-pollinator
      interactions and genetic diversity in the self-compatible Betonica officinalis.
      We examined the abundance and composition of pollinators, the foraging behaviour
      of bumblebees and the performance, outcrossing rate and genetic diversity of B.
      officinalis after 2 and 6 years in experimentally fragmented nutrient-poor,
      calcareous grassland in the northern Swiss Jura mountains. Fragments of different
      size (2.25 and 20.25 m(2)) were isolated by a 5-m-wide strip of frequently mown
      vegetation. Control plots of corresponding size were situated in adjacent
      undisturbed grassland. Experimental grassland fragmentation altered the
      composition of B. officinalis pollinators and reduced their flower visitation
      rate. Furthermore, the foraging behaviour of bumblebees was changed in the
      fragments. After 6 years of fragmentation seed weight was higher in fragments
      than in control plots. However, the densities of B. officinalis rosettes and
      inflorescences, plant height and inflorescence length were not affected by
      fragmentation. The outcrossing frequency of B. officinalis growing in fragments
      was reduced by 15% after 2 years and by 33% after 6 years of experimental
      fragmentation. This resulted in a significant reduction of the genetic diversity
      in seedlings emerging in fragments after 6 years. Our study shows that small
      scale habitat fragmentation can disturb the interaction between B. officinalis
      and pollinators resulting in a reduced outcrossing frequency and genetic
      diversity in plants growing in fragments. However, the response to fragmentation
      was considerably delayed. This finding strengthens the claim for long-term field
      experiments with proper replications and controls to assess delayed effects of
      habitat fragmentation.

PMID- 20155290
TI  - Surface characteristics of isopod digestive gland epithelium studied by SEM.
AB  - The structure of the digestive gland epithelium of a terrestrial isopod Porcellio
      scaber has been investigated by conventional scanning electron microscopy (SEM),
      focused ion beam-scanning electron microscopy (FIB/SEM), and light microscopy in
      order to provide evidence on morphology of the gland epithelial surface in
      animals from a stock culture. We investigated the shape of cells, extrusion of
      lipid droplets, shape and distribution of microvilli, and the presence of
      bacteria on the cell surface. A total of 22 animals were investigated and we
      found some variability in the appearance of the gland epithelial surface.
      Seventeen of the animals had dome-shaped digestive gland "normal" epithelial
      cells, which were densely and homogeneously covered by microvilli and varying
      proportions of which extruded lipid droplets. On the surface of microvilli we
      routinely observed sparsely distributed bacteria of different shapes. Five of the
      22 animals had "abnormal" epithelial cells with a significantly altered shape. In
      three of these animals, the cells were much smaller, partly or completely flat or
      sometimes pyramid-like. A thick layer of bacteria was detected on the
      microvillous border, and in places, the shape and size of microvilli were
      altered. In two animals, hypertrophic cells containing large vacuoles were
      observed indicating a characteristic intracellular infection. The potential of
      SEM in morphological investigations of epithelial surfaces is discussed.

PMID- 20155289
TI  - HNF1B alterations associated with congenital anomalies of the kidney and urinary
      tract.
AB  - Hepatocyte nuclear factor 1beta (HNF1beta) abnormalities have been recognized to
      cause congenital anomalies of the kidney and urinary tract (CAKUT), predominantly
      affecting bilateral renal malformations. To further understand the spectrum of
      HNF1beta related phenotypes, we performed HNF1B gene mutation and deletion
      analyses in Japanese patients with renal hypodysplasia (n = 31), unilateral
      multicystic dysplastic kidney (MCDK; n = 14) and others (n = 5). We identified
      HNF1B alterations in 5 out of 50 patients (10%). De novo heterozygous complete
      deletions of HNF1B were found in 3 patients with unilateral MCDK. Two of the
      patients showed contralateral hypodysplasia, whereas the other patient showed a
      radiologically normal contralateral kidney with normal renal function. Copy
      number variation analyses showed 1.4 Mb microdeletions involving the whole HNF1B
      gene with breakpoints in flanking segmental duplications. We also identified 1
      novel truncated mutation (1007insC) and another missense mutation (226G>T) in
      patients with bilateral hypodysplasia. HNF1B alterations leading to
      haploinsufficiency affect a diverse spectrum of CAKUT. The existence of a patient
      with unilateral MCDK with normal renal function might provide genetic insight
      into the etiology of these substantial populations of only unilateral MCDK. The
      recurrent microdeletions encompassing HNF1B could have a significant impact on
      the mechanism of HNF1B deletions.

PMID- 20155292
TI  - Symptomatic linea arcuata hernia.
AB  - Hernias are often associated with congenital defects or incisional breakdown.
      Even though most of the linea arcuata hernias are asymptomatic, we present a rare
      case of a symptomatic linea arcuata hernia with associated internal herniation of
      the colon sigmoideum in a woman without previous abdominal surgery.

PMID- 20155293
TI  - Observation of cavitation pits on mechanical heart valve surfaces in an
      artificial heart used in in vitro testing.
AB  - Our group has developed an electrohydraulic total artificial heart (EHTAH) with
      two diaphragm-type blood pumps. Cavitation in a mechanical heart valve (MHV)
      causes valve surface damage. The objective of this study was to investigate the
      possibility of estimating the MHV cavitation intensity using the slope of the
      driving pressure just before valve closure in this artificial heart. Twenty-five
      and twenty-three-millimeter Medtronic Hall valves were mounted at the inlet and
      outlet ports, respectively, of both pumps. The EHTAH was connected to the
      experimental endurance tester developed by our group, and tested under
      physiological pressure conditions. Cavitation pits could be seen on the inlet
      valve surface and on the outlet valve surface of the right and left blood pumps.
      The pits on the inlet valves were more severe than those on the outlet valves in
      both blood pumps, and the cavitation pits on the inlet valve of the left blood
      pump were more severe than those on the inlet valve of the right blood pump. The
      longer the pump running time, the more severe the cavitation pits on the valve
      surfaces. Cavitation pits were concentrated near the contact area with the valve
      stop. The major cause of these pits was the squeeze flow between the leaflet and
      valve stop.

PMID- 20155294
TI  - Artificial organs: recent progress in metals and ceramics.
AB  - The superior properties and novel functions of biomaterials, including metals and
      ceramics commonly used as implants and medical devices, have been the focus of a
      number of recent papers. New functions have been explored in metastable beta-Ti
      alloys, Ni-free Co-Cr-Mo alloys, Mg alloys, and other materials. In addition,
      porous metals and ceramics with sophisticated structures have been studied as
      scaffolds for regenerative medicine. In this review, recent advances in
      bioceramics, metallic biomaterials, and their composites are discussed in terms
      of their material properties and morphology.

PMID- 20155295
TI  - Off-label use of rituximab in systemic lupus erythematosus: a systematic review.
AB  - Considerable interest in the efficacy of rituximab (a monoclonal CD20 antibody)
      in patients with systemic lupus erythematosus (SLE) has been generated due to its
      unique mode of action, culminating in a series of randomized and open trials, and
      case reports. However, this use is off-license and two significant RCTs have
      reported negative findings, reopening the debate on clinical benefit. This review
      of the available data suggests that rituximab induces B-cell depletion in 95% of
      patients, and a significant reduction in disease activity is achieved with a
      relatively good safety profile in patients with SLE.

PMID- 20155297
TI  - Removal of orange eyebrow tattoo in a single session with the Q-switched Nd:YAG
      532-nm laser.

PMID- 20155296
TI  - Prevalence and accessory gene regulator (agr) analysis of vancomycin-intermediate
      Staphylococcus aureus among methicillin-resistant isolates in Taiwan--SMART
      program, 2003.
AB  - The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in
      nosocomial staphylococcal infections in Taiwan has exceeded 50% since 2000.
      However, little relevant data has been available concerning vancomycin
      intermediate S. aureus (VISA) and heteroresistant VISA (hVISA). We collected
      1,000 MRSA isolates from ten medical center hospitals in Taiwan during 2003. All
      were initially screened for reduced susceptibility to vancomycin on brain heart
      infusion (BHI) agar containing 5 mg/L vancomycin. Among 34 MRSA isolates that
      grew on the screening plates, two VISA isolates (0.2%) and seven hVISA isolates
      (0.7%) were evident. Vancomycin-resistant S. aureus was not detected. The
      accessory gene regulator (agr) typing of all 1,000 MRSA strains were typed by
      multiplex polymerase chain reaction (PCR); 919 strains (91.9%) including the VISA
      and hVISA isolates belonged to agr group I, 78 strains (7.8%) were agr group II,
      two strains (0.2%) were agr group III, and one isolate (0.1%) was agr group IV.
      There was no relationship between sample sites and agr typing. In 2003, the
      incidence of hVISA and VISA in Taiwan was low. Continued surveillance is
      recommended, given the implementation of new Clinical and Laboratory Standards
      Institute (CLSI) criteria for S. aureus and the increasing clinical use of
      glycopeptides.

PMID- 20155298
TI  - Safe use of landiolol hydrochloride in a patient with marked pseudocholinesterase
      deficiency.

PMID- 20155299
TI  - Effectiveness of preventive oral health care in Hispanic children living near US
      Mexico border.
AB  - OBJECTIVE: The effect of preventive oral healthcare on dental caries in Hispanic
      children in a school district near the US-Mexico border in Texas was studied.
      METHODS: We collected socioeconomic and demographic data for enrolled students
      through a written survey of parents. The information was linked to screening data
      for students in the same school that had been collected during a previously
      completed teledentistry demonstration project. The presence of dental sealants
      served as a proxy for preventive oral healthcare. We compared the effect of
      sealant presence on caries. The student population was 97.5% Hispanic and 82%
      were economically disadvantaged. RESULTS: Forty-four percent of the children in
      our study sample had caries. The prevalence of sealants was 19%; 32% is the
      national average. The results of regression models confirm the hypothesis that
      preventive services significantly reduce the occurrence of dental caries (OR =
      0.241, P < 0.01). Higher household income (OR = 0.437, P < 0.05) and parent
      health insurance (OR = 0.497, P < 0.05) were also associated with reduced caries
      incidence. CONCLUSIONS: Our study suggests that preventive services reduce the
      incidence of caries in Hispanic children in the study population.

PMID- 20155300
TI  - How does chytrid infection vary among habitats? The case of Litoria wilcoxii
      (Anura, Hylidae) in SE Queensland, Australia.
AB  - Most analyses dealing with the geographical distribution of the chytrid fungus
      (Batrachochytrium dendrobatidis) have been performed on large geographical scales
      and data on more localized distribution of the chytrid within catchments are
      scarce. In this study, we compare the prevalence and intensity of infection of
      chytrid within and outside rainforest habitats at five independent catchments in
      southeast Queensland. In each catchment, we sampled adult Litoria wilcoxii along
      two transects on the same stream: one in forested areas, and the other in open
      nearby farmland. We analyzed swabs using quantitative PCR techniques. Male frogs
      were in higher densities in open habitats compared with the nearby forested
      areas. Infected male frogs were found in all catchments surveyed; however,
      prevalence of B. dendrobatidis in adult males was higher in the forested habitats
      than in the open habitats in four of the catchments. There was no significant
      difference in intensity of infection between forested and open habitats. For
      adult females and juveniles, sample sizes were not high enough for comparisons.
      Our results suggest that habitat influences chytrid prevalence and open areas may
      provide refuge from chytrid-induced population declines.

PMID- 20155301
TI  - Aerial dispersal and multiple-scale spread of epidemic disease.
AB  - Disease spread has traditionally been described as a traveling wave of constant
      velocity. However, aerially dispersed pathogens capable of long-distance
      dispersal often have dispersal gradients with extended tails that could result in
      acceleration of the epidemic front. We evaluated empirical data with a simple
      model of disease spread that incorporates logistic growth in time with an inverse
      power function for dispersal. The scale invariance of the power law dispersal
      function implies its applicability at any spatial scale; indeed, the model
      successfully described epidemics ranging over six orders of magnitude, from
      experimental field plots to continental-scale epidemics of both plant and animal
      diseases. The distance traveled by epidemic fronts approximately doubled per unit
      time, velocity increased linearly with distance (slope ~(1/2)), and the exponent
      of the inverse power law was approximately 2. We found that it also may be
      possible to scale epidemics to account for initial outbreak focus size and the
      frequency of susceptible hosts. These relationships improve understanding of the
      geographic spread of emerging diseases, and facilitate the development of methods
      for predicting and preventing epidemics of plants, animals, and humans caused by
      pathogens that are capable of long-distance dispersal.

PMID- 20155302
TI  - The lactoferrin receptor complex in Gram negative bacteria.
AB  - Bacteria that inhabit the respiratory and genitourinary tracts of mammals
      encounter an iron-deficient environment on the mucosal surface where iron is
      complexed by the host iron-binding proteins transferrin and lactoferrin.
      Lactoferrin is also present in high concentrations at sites of inflammation where
      the cationic anti-microbial peptide lactoferricin is produced by proteolysis of
      lactoferrin. Several members of the Neisseriaceae and Moraxellaceae families
      express surface receptors, capable of specifically binding host lactoferrin and
      extracting the iron from lactoferrin as a source of iron for growth. The receptor
      is comprised of an integral outer membrane protein, lactoferrin binding protein A
      (LbpA), and a largely exposed surface lipoprotein, lactoferrin binding protein B
      (LbpB). LbpA is essential for mediating growth using lactoferrin as a sole iron
      source whereas LbpB only plays a facilitating role. LbpB, with the presence of a
      large tract of negatively charged residues, appears to protect the bacterial cell
      from the bactericidal effects of the lactoferricin. The lactoferrin receptors in
      these species appear to be essential for survival and thus may serve as potential
      vaccine targets.

PMID- 20155304
TI  - Spatial variability and temporal trends of HCH and DDT in soils around Beijing
      Guanting Reservoir, China.
AB  - Spatial variability and temporal trends in concentrations of the organochlorine
      pesticides (OCPs), hexachlorocyclohexane (HCH) and
      dichlorodiphenyltrichloroethane (DDT), in surface soils around Beijing Guanting
      Reservoir (GTR) were studied in 2003 and 2007. Concentrations of the two OCPs in
      soils around GTR were generally less than reference values set by the Chinese
      government for the protection of agricultural production and human health. Among
      the OCPs, beta-HCH and p, p'-DDE were the two predominant compounds. This result
      indicates that the HCH and DDT residues in soils were primarily from historical
      use. Based on kriging, a spatial distribution of HCH and DDT around the GTR was
      observed. Spatial variability indicated how HCH and DDT had been applied and been
      distributed in the past. Between 2003 and 2007, concentrations of HCH and DDT
      decreased more rapidly in orchard soils than those in fallow soils.

PMID- 20155305
TI  - The relationship between aversive conditioning and risk-avoidance in gambling.
AB  - This study investigated the relationship between aversive conditioning, heart
      rate variability suppression, behavioral activation system/behavioral inhibition
      system and risk-avoidance on the Iowa gambling task (IGT) in a nonclinical sample
      (29 male, 29 female, mean age = 20.7). A laboratory based Pavlovian aversive
      conditioning paradigm was used where a 1500 Hz tone (CS+) was followed by a burst
      of loud white noise (US), and a 850 Hz (CS-) tone was never followed by the US.
      In a subsequent extinction phase where the CS+ and CS- were presented without the
      US, conditioned skin conductance responses to the CS+ indicated aversive
      conditioning. The results showed that the participants who did not show aversive
      conditioning (N = 26) exhibited significantly less risk-avoidance compared to
      participants who did show aversive conditioning (N = 32). Regression analysis
      showed that among the study variables, only aversive conditioning contributed
      significantly to explaining variance in risk-avoidance. These results may have
      implications for understanding risk-taking in gambling in general, and may be a
      starting point understanding the role of aversive conditioning in the development
      and maintenance of gambling problems.

PMID- 20155306
TI  - Leak in the breathing circuit: CO2 absorber and human error.
AB  - A couple of reports in literature have mentioned CO2 absorbers to be the cause
      for breathing circuit leak during anesthesia. Defective canister, failure to
      close the absorber chamber and overfilling of the chamber with sodalime were the
      problems in these reports. Among these, the last two are reports of human error
      resulting in problems. We report a case where despite taking precautions in this
      regard, we experienced a significant leak in the system due to a problem with the
      CO2 absorber, secondary to human error.

PMID- 20155303
TI  - Identification and characterization of NARROW AND ROLLED LEAF 1, a novel gene
      regulating leaf morphology and plant architecture in rice.
AB  - Leaf morphology is an important agronomic trait in rice breeding. We isolated
      three allelic mutants of NARROW AND ROLLED LEAF 1 (nrl1) which showed phenotypes
      of reduced leaf width and semi-rolled leaves and different degrees of dwarfism.
      Microscopic analysis indicated that the nrl1-1 mutant had fewer longitudinal
      veins and smaller adaxial bulliform cells compared with the wild-type. The NRL1
      gene was mapped to the chromosome 12 and encodes the cellulose synthase-like
      protein D4 (OsCslD4). Sequence analyses revealed single base substitutions in the
      three allelic mutants. Genetic complementation and over-expression of the OsCslD4
      gene confirmed the identity of NRL1. The gene was expressed in all tested organs
      of rice at the heading stage and expression level was higher in vigorously
      growing organs, such as roots, sheaths and panicles than in elsewhere. In the
      mutant leaves, however, the expression level was lower than that in the wild
      type. We conclude that OsCslD4 encoded by NRL1 plays a critical role in leaf
      morphogenesis and vegetative development in rice.

PMID- 20155308
TI  - Smoking cessation in the WIC program.

PMID- 20155309
TI  - Pilot randomized controlled trial of Reciprocal Imitation Training for teaching
      elicited and spontaneous imitation to children with autism.
AB  - Children with autism exhibit significant deficits in imitation skills. Reciprocal
      Imitation Training (RIT), a naturalistic imitation intervention, was developed to
      teach young children with autism to imitate during play. This study used a
      randomized controlled trial to evaluate the efficacy of RIT on elicited and
      spontaneous imitation skills in 21 young children with autism. Results found that
      children in the treatment group made significantly more gains in elicited and
      spontaneous imitation, replicating previous single-subject design studies. Number
      of spontaneous play acts at pre-treatment was related to improvements in
      imitation during the intervention, suggesting that children with a greater play
      repertoire make greater gains during RIT.

PMID- 20155310
TI  - Glutamate transporter gene (SLC1A1) single nucleotide polymorphism (rs301430) and
      repetitive behaviors and anxiety in children with autism spectrum disorder.
AB  - Investigated association of single nucleotide polymorphism (SNP) rs301430 in
      glutamate transporter gene (SLC1A1) with severity of repetitive behaviors
      (obsessive-compulsive behaviors, tics) and anxiety in children with autism
      spectrum disorder (ASD). Mothers and/or teachers completed a validated DSM-IV
      referenced rating scale for 67 children with autism spectrum disorder. Although
      analyses were not significant for repetitive behaviors, youths homozygous for the
      high expressing C allele had more severe anxiety than carriers of the T allele.
      Allelic variation in SLC1A1 may be a biomarker for or modifier of anxiety symptom
      severity in children with ASD, but study findings are best conceptualized as
      tentative pending replication with larger independent samples.

PMID- 20155311
TI  - Cocksfoot mottle sobemovirus coat protein contains two nuclear localization
      signals.
AB  - Cocksfoot mottle virus (CfMV) coat protein (CP) localization was studied in plant
      and mammalian cells. Fusion of the full-length CP with enhanced green fluorescent
      protein (EGFP) localized to the cell nucleus whereas similar constructs lacking
      the first 33 N-terminal amino acids of CP localized to the cytoplasm. CP and EGFP
      fusions containing mutations in the arginine-rich motif of CP localized to the
      cytoplasm and to the nucleus in plant cells indicating the involvement of the
      motif in nuclear localization. In mammalian cells, mutations in the arginine-rich
      region were sufficient to completely abolish nuclear transport. The analysis of
      deletions of amino acid residues 1-11, 1-22, and 22-33 of CP demonstrated that
      there were two separate nuclear localization signals (NLS) within the N-terminus-
      a strong NLS1 in the arginine-rich region (residues 22-33) and a weaker NLS2
      within residues 1-22. Analysis of point mutants revealed that the basic amino
      acid residues in the region of the two NLSs were individually not sufficient to
      direct CP to the nucleus. Additional microinjection studies with fluorescently
      labeled RNA and CP purified from CfMV particles demonstrated that the wild-type
      CP was capable of transporting the RNA to the nucleus. This feature was not
      sequence-specific in transient assays since both CfMV and GFP mRNA were
      transported to the cell nucleus by CfMV CP. Together the results suggest that the
      nucleus may be involved in CfMV infection.

PMID- 20155312
TI  - Genomic analysis of two Chinese strains of porcine reproductive and respiratory
      syndrome viruses with different virulence.
AB  - Two strains of porcine reproductive and respiratory syndrome virus (PRRSV) were
      isolated, designated GDQJ and GDBY1. Experimental inoculation showed that GDBY1,
      caused 100% morbidity and 67% mortality, while GDQJ, caused 100% morbidity but no
      death. Full-length genomes were sequenced. Homologic and phylogenetic analyses
      indicated that these two strains were closely related to Chinese highly
      pathogenic PRRSV strains. Surprisingly, identical 30 amino acids (aa) deletion in
      the NSP2-coding region, a presumed high virulence marker, was present in low
      virulent strain GDQJ. Further comprehensive analysis of GDQJ genome in comparison
      with Chinese highly pathogenic PRRSV strains revealed multiple genomic
      variations, distributing in 5' UTR, NSP1b, NSP2, NSP3, NSP5, NSP7, NSP9, NSP10,
      GP5, and N regions. Data present in this article confirm that the 30 aa deletion
      in the NSP2-coding region alone is not a reliable genomic indicator for the high
      virulence of PRRSV strains emerged in China. The genomic variations of GDQJ
      strain provided the basis for further studies of virulence determinants for
      PRRSVs.

PMID- 20155313
TI  - Occupational exposure to terbufos and the incidence of cancer in the Agricultural
      Health Study.
AB  - OBJECTIVE: Terbufos is the fourth most commonly used organophosphate insecticide
      (OP) in the United States. Terbufos has not been demonstrated to be carcinogenic
      in rodents, although non-arsenical insecticides, including OPs, have been
      associated with excess cancer in epidemiologic studies. We investigated
      associations between use of terbufos and the incidence of cancer. METHODS: The
      Agricultural Health Study is a prospective cohort study of 57,310 licensed
      pesticide applicators from Iowa and North Carolina. Detailed information about 50
      pesticides, including terbufos, and potential confounders was obtained from self
      administered questionnaires. Terbufos intensity-weighted lifetime exposure-days
      were defined as (lifetime exposure-days) x (exposure intensity score). Cases
      include all first primary cancers diagnosed between enrollment and December 31,
      2005. Hazard ratios (HR) and 95% CI were calculated with Cox proportional hazards
      models, adjusting for potential confounders. RESULTS: Overall cancer risk was
      slightly increased among terbufos users [HR 1.21 (1.06-1.37)]. Suggestive
      associations were observed between terbufos use and cancers of the prostate
      (HR(highest tertile) = 1.21; 95% CI = 0.99-1.47) and lung (HR(middle tertile) =
      1.45; 95% CI = 0.95-2.22) and leukemia (HR(middle tertile) = 2.38; 95% CI = 1.35
      4.21) and non-Hodgkin's lymphoma (HR(middle tertile) = 1.94; 95% CI = 1.16-3.22),
      although the exposure-response gradients were non-monotonic and p for trends were
      not significant. CONCLUSION: We found suggestive associations between
      occupational terbufos use and several cancer sites. However, cautious
      interpretation of these results is warranted by the lack of existing experimental
      and epidemiologic evidence to support carcinogenic effects of terbufos.

PMID- 20155314
TI  - Alcohol and risk of breast cancer in Mexican women.
AB  - BACKGROUND: Little is known about the relationship between alcohol intake and
      breast cancer risk among Mexican women. This association may be modified by
      folate and Vitamin B12. METHODS: A population-based case-control study conducted
      in Mexico recruited 1,000 incident breast cancer cases aged 35-69 and 1,074
      controls matched on age, region, and health care system. In-person interviews
      were conducted to assess breast cancer risk factors and recent diet using a food
      frequency questionnaire. Conditional logistic regression models estimated
      adjusted odds ratios and 95% confidence intervals. RESULTS: Over one-half (57%)
      of cases and less than one-half of controls (45%) reported any lifetime alcohol
      consumption. Compared with never drinkers, women reporting ever drinking
      (Adjusted OR = 1.25, 95% CI = 0.99-1.58) had a greater odds of breast cancer.
      There was evidence for interaction in the association between ever consuming any
      alcohol and breast cancer by folate (p for interaction = 0.04) suggesting women
      with lower folate intake had a higher odds of breast cancer (Adjusted OR = 1.99,
      95% CI = 1.26-3.16) compared to women with higher folate intake (OR = 1.12, 95%
      CI = 0.69-1.83). CONCLUSIONS: Our findings support evidence that any alcohol
      intake increases risk of breast cancer. Insufficient intake of folate may further
      elevate risk for developing breast cancer among women who consume alcohol.

PMID- 20155315
TI  - S-phase progression in mammalian cells: modelling the influence of nuclear
      organization.
AB  - The control of DNA replication is of fundamental importance as cell proliferation
      demands that identical copies of the genetic material are passed to the two
      daughter cells that form during mitosis. These genetic copies are generated in
      the preceding S phase, where the entire DNA complement of the mother cell must be
      copied exactly once. As part of this process, it is known that different regions
      of mammalian genomes are replicated at specific times of a temporally defined
      replication programme. The key feature of this programme is that active genes in
      euchromatin are replicated before inactive ones in heterochromatin. This
      separation of S phase into periods where different classes of chromatin are
      duplicated is important in maintaining changes in gene expression that define
      individual cell types. Recent attempts to understand the structure of the S-phase
      timing programme have focused on the use of genome-wide strategies that
      inevitably use DNA isolated from large cell populations for analysis. However,
      this approach provides a composite view of events that occur within a population
      without knowledge of the cell-to-cell variability across the population. In this
      review, we attempt to combine information generated using genome-wide and single
      cell strategies in order to develop a coherent molecular understanding of S-phase
      progression. During this integration, we have explored how available information
      can be introduced into a modelling environment that best describes S-phase
      progression in mammalian cells.

PMID- 20155316
TI  - Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to
      chemotherapy in breast tumor cells.
AB  - Studies were performed to determine the influence of the phosphodiesterase-5
      inhibitor, sildenafil, on sensitivity to adriamycin (doxorubicin) in four human
      breast tumor cell lines and one murine breast tumor line. Sildenafil did not
      interfere with the effectiveness of adriamycin in any of the cell lines tested.
      Sildenafil also failed to protect MDA-MB231 cells against the cytotoxicity of
      cisplatin, taxol or camptothecin. Sildenafil enhanced sensitivity to adriamycin
      markedly in the p53 mutant MDA-MB231 and p53 null MCF-7/E6 cells and moderately
      in the MCF-7/caspase 3 and 4T1 cell lines. In the MDA-MB231 cells, sildenafil
      increased the extent of DNA damage induced by adriamycin as well as the extent of
      apoptotic cell death. Sildenafil did not influence sensitivity to adriamycin in
      bone marrow cells or macrophages. In an immunocompetent model of breast cancer
      (4T1 mammary carcinoma in Balb/c mice), sildenafil did not attenuate the
      antitumor effects of adriamycin; furthermore, the combination of sildenafil with
      adriamycin was no more toxic to the animals than adriamycin alone. Given that
      sildenafil has been shown to have the potential to protect the heart against the
      toxicity of adriamycin, these studies suggest that the inclusion of sildenafil
      with conventional chemotherapeutic protocols involving adriamycin (and possibly
      cisplatin, camptothecin and/or paclitaxel) should not compromise the antitumor
      effectiveness of these drugs nor enhance their toxicity to the patient.

PMID- 20155317
TI  - The impact of ground-level fireworks (13 km long) display on the air quality
      during the traditional Yanshui Lantern Festival in Taiwan.
AB  - In this study, the concentrations of CO, non-methane hydrocarbons, NO(X), SO(2),
      benzene, toluene, ethylbenzene, xylene (BTEX), PM10, and PM2.5 were continuously
      monitored before and after the fireworks display during the traditional Lantern
      Festival from March 2-7, 2007 in Yanshui Town, Taiwan. Major roads in Yanshui
      Town were surrounded by fireworks 13 km in length, with the display lasting for
      45 min. More than 200 small firecracker towers popped up randomly in town,
      resulting in exceedingly inhomogeneous air quality until the end of display at
      03:00 the next day, March 5. During the fireworks display, the hourly
      concentration of PM10 and PM2.5 at Yanshui Primary School reached about 429 and
      250 MUg m-3, respectively, which is 10 times the normal level, and 6 s values
      even went as high as 1,046 and 842 MUg m-3, respectively. Similarly, BTEX
      concentration went up to about five to 10 times its normal value during the
      fireworks display. As indicated by the distribution of submicron particle sizes,
      the number of particles with a diameter less than 100 nm increased abruptly
      during the event period. Metal components with concentrations of more than 10
      times higher than the normal value at Yanshui Primary School were Sr, K, Ba, Pb,
      Al, Mg, and Cu, in sequence. Among water-soluble ions, the content of K( + ),
      Mg2( + ), and Cl( - ) increased the most, all of which were related to the
      materials used in the fireworks. The results of this study indicate that
      fireworks can cause an abrupt increase in the concentration of trace substances
      in the air within a short period. Although the risks of these trace substances on
      public health remain to be further assessed, the study results can be utilized in
      the management of folk events.

PMID- 20155318
TI  - Cornel iridoid glycoside inhibits inflammation and apoptosis in brains of rats
      with focal cerebral ischemia.
AB  - The capacity of cornel iridoid glycoside (CIG) to suppress the manifestations of
      ischemic stroke was investigated. CIG was administered to rats by the
      intragastric route once daily for 7 days. Focal cerebral ischemia was induced by
      2 h of middle cerebral artery occlusion followed by 24 h of reperfusion. In non
      treated rats large infarct areas were observed within 24 h of reperfusion.
      Examination of the ischemic cerebral cortex revealed microglia and astrocyte
      activation, increased interleukin-1beta (IL-1 beta) and tumor necrosis factor
      alpha (TNF-alpha) concentrations, increased DNA fragmentation in the ischemia
      penumbra, elevated Bax expression, increased caspase-3 cleavage, and decreased
      Bcl-2 expression. Pretreatment with CIG decreased the infarct area, DNA
      fragmentation, IL-1beta and TNF-alpha concentrations, microglia and astrocyte
      activation, Bax expression, and caspase-3 cleavage while increasing Bcl-2
      expression. CIG exerts anti-neuroinflammatory and anti-apoptotic effects which
      should prove beneficial for prevention or treatment of stroke.

PMID- 20155319
TI  - The impact of ulcerative colitis on patients' lives compared to other chronic
      diseases: a patient survey.
AB  - PURPOSE: This study was designed to identify the impact chronic ulcerative
      colitis (UC) has on the lives of patients compared to other chronic conditions.
      Overall, 451 patients with UC, 309 with rheumatoid arthritis, 305 with asthma,
      and 305 with migraine headaches were recruited in an Internet survey designed to
      assess a variety of disease-impact indices. RESULTS: Patients with UC reported a
      mean of eight (self-defined) flare-ups in the previous 12 months. Significantly
      more patients with UC (81%) believed that the quantity of flare-ups they
      experienced was 'normal', compared to patients with migraine headaches (64%) or
      asthma (75%). Patients with UC also reported significantly more worry about
      disease complications (84%), depression (62%), and embarrassment (70%) than
      patients with the other chronic conditions. CONCLUSIONS: Compared to patients
      with other chronic conditions, patients with UC perceive substantially more
      negative impact upon their lives, especially with regard to the psychological
      burden.

PMID- 20155320
TI  - Rifaximin and Crohn's disease: a new solution to an old problem?

PMID- 20155321
TI  - Glutaraldehyde-induced chemical colitis versus ischemic colitis.

PMID- 20155322
TI  - Clinical outcomes after self-expanding plastic stent placement for refractory
      benign esophageal strictures.
AB  - BACKGROUND: Refractory benign esophageal strictures (RBES) are defined as those
      that persist structurally and symptomatically after repeated dilation sessions.
      Small series have reported favorable outcomes after placement and subsequent
      removal of Polyflex self-expanding plastic stents (SEPS). AIMS: To characterize
      the outcomes after Polyflex stent placement in patients with RBES. METHODS:
      Outcomes of consecutive patients who underwent Polyflex stent placement for RBES
      between April 15, 2005 and November 20, 2006 were analyzed retrospectively. The
      etiology of the stricture, number of dilations prior to initial SEPS placement,
      size of stent placed, stricture resolution after SEPS removal, cases of stent
      migration, duration of SEPS placement, time to repeat dilation and/or SEPS
      replacement after stent removal, and complications were assessed. RESULTS: Twenty
      three Polyflex stents were placed in 13 patients suitable for analysis. The
      majority of stenoses (11/13) were attributable to anastomotic strictures after
      curative esophagogastrectomy for esophageal neoplasms. All 11 patients in this
      group had satisfactory relief of dysphagia to solids determined clinically with
      indwelling SEPS placement. SEPS migration occurred in seven instances (30% of
      SEPS placed). Dysphagia remediation after subsequent SEPS removal was observed in
      only three patients (23%). Placement of a partially covered metal stent within a
      Polyflex stent was necessary in one case due to epithelial hyperplasia. The mean
      time for repeat dilation and/or SEPS reinsertion due to recurrent dysphagia after
      stent removal was 37 days (range 6-120 days). CONCLUSIONS: Polyflex stents
      provided satisfactory palliation of dysphagia for RBES while in place. However,
      unplanned SEPS migration and dysphagia recurrence after stent removal were
      common.

PMID- 20155323
TI  - Significance of palisading longitudinal esophagus vessels: identification of the
      true esophagogastric junction has histopathological and oncological
      considerations.
AB  - BACKGROUND: Identification of the true esophagogastric junction (EGJ) is
      essential for diagnosis of Barrett's esophagus. AIMS: To determine whether the
      lower end of palisading longitudinal esophagus vessels (PLEV) is a novel and
      reliable marker for histological identification of the EGJ, and to investigate
      how short-segment Barrett's esophagus develops. METHODS: Using 87 formalin-fixed
      esophagogastrectomy specimens of squamous cell carcinoma of upper or middle
      esophagus, the entire lower esophagus area including the putative EGJ was
      histologically examined. The EGJ was first determined on each longitudinal
      section by the most distal end of the esophageal glands proper, squamous islands,
      or multilayered epithelium. The most distal end of PLEV was identified
      thereafter. If this end was distal to the above markers, it was judged as the
      novel point of the EGJ. A circular reference line was set to the middle level of
      the angle of His. Distances from this line to the squamocolumnar junction (SCJ)
      or EGJ were measured. RESULTS: The distances to the SCJ or EGJ on the lesser
      curvature side were significantly longer than those on the greater curvature side
      (P < 0.0001). The extent of Barrett's epithelium was significantly longer on the
      lesser curvature side than on the greater curvature side (P < 0.005). The SCJ
      line, the conventional EGJ line, and the EGJ line determined by conventional
      factors combined with the most distal end of PLEV were located proximal to
      distal, in that order (P < 0.0001). CONCLUSIONS: The lower end of PLEV is a
      feasible histological marker of the EGJ.

PMID- 20155324
TI  - HIV awareness of outgoing female migrant workers of Bangladesh: a pilot study.
AB  - Female migrant workers face a growing scale of unsafe migration, which increases
      their risk of HIV. Despite this, increasing numbers of women are migrating from
      Bangladesh to other countries as contractual workers. The aim of the study is to
      establish a baseline for the socio-demographic status of female migrant workers
      and the extent of their HIV/AIDS awareness along with the factors that determine
      it, and to discuss the need for effective HIV awareness programmes. During June
      July 2008 data were collected by a questionnaire from 123 participants by
      approaching a cross section of women at the airport who were ready to fly to take
      up an overseas job. A total of 87% had heard of HIV/AIDS. Participants who had
      completed an education level of year >=8 were more likely to have been informed
      about HIV than others. The average score in correct identification of modes of
      HIV infection was 1.6 (out of 4) and for preventive measures 1.8 (out of 5).
      Television and health workers were the major sources of HIV related knowledge.
      HIV-knowledge among the potential female migrant workers seems to be poor. As
      growing numbers of female workers are moving overseas for work, government and
      other concerned agencies must take a pro-active role to raise their awareness of
      HIV/AIDS infection and of effective preventive measures.

PMID- 20155325
TI  - Strategies for successful retention of Alaska Native and American Indian study
      participants.
AB  - This paper reports the strategies used to track and follow 3,828 Alaska Native
      and American Indian study participants in the city of Anchorage and more rural
      areas of Alaska and provides characteristics of respondents and non-respondents.
      Over 88% were successfully followed-up, with 49% of respondents completed in
      three or fewer attempts. Follow-up completion rates were significantly higher for
      women, those living in a rural area, over age 55, married, employed, having a
      higher household income, and at current residence for more than five years.
      Follow-up of large numbers of Alaska Native and American Indian people living in
      geographically diverse areas is feasible, although challenging. Successful
      strategies to avoid attrition include using telephones as the primary method of
      contact; using a computerized contact relationship management system to track
      efforts and manage data; obtaining contact information from participant contact
      networks, medical records, and community networks; using local village
      interviewers to contact participants without telephone service; and mailing paper
      questionnaires to participants who are incarcerated or use social services.

PMID- 20155326
TI  - Healthcare apartheid and quality of life for people with disabilities.

PMID- 20155327
TI  - No negative effects of a multi-factorial, intensified treatment on self-reported
      health status, treatment satisfaction, and diabetes-related distress in screen
      detected type 2 diabetes patients. The ADDITION-Netherlands study.
AB  - PURPOSE: To examine the effects of a multi-factorial, intensified treatment on
      self-reported health status, treatment satisfaction, and diabetes-related
      distress in screen-detected type 2 diabetes patients. METHODS: Cluster-randomised
      controlled trial; A total of 498 screen-detected type 2 diabetes patients from 79
      general practices were assigned to intensified (n = 255) or routine treatment
      according to Dutch guidelines (n = 243). At baseline and after 3 years, patients
      completed the Short Form-36 and the European Quality of Life-5 Dimensions
      questionnaires. After 4.5 years, patients completed the Diabetes Treatment
      Satisfaction Questionnaire and the Problem Areas In Diabetes scale. We analysed
      the effects of intensified treatment on self-rated health status, treatment
      satisfaction, and diabetes-related distress, using random effects models to
      account for clustering at practice level. RESULTS: Three to 5 years after type 2
      diabetes was detected by screening, there were no differences between intensified
      and routine treatment in self-reported health status, treatment satisfaction, and
      diabetes-related distress. CONCLUSIONS: Multi-factorial, intensified treatment
      did not influence self-rated health status, treatment satisfaction, and distress
      in screen-detected type 2 diabetes patients. Therefore, health care professionals
      do not have to fear negative effects of an intensified treatment on these
      psychological outcomes.

PMID- 20155328
TI  - Constitutive nitric oxide synthase-mediated caspase-3 S-nitrosylation in ghrelin
      protection against Porphyromonas gingivalis-induced salivary gland acinar cell
      apoptosis.
AB  - Recent advances in identifying the salivary constituents capable of influencing
      the oral mucosal inflammatory responses have brought to focus the importance of a
      peptide hormone, ghrelin. Here, we report on the involvement of ghrelin in
      controlling the apoptotic processes induced in sublingual salivary gland acinar
      cells by the lipopolysaccharide (LPS) of a periodontopathic bacterium,
      Porphyromonas gingivalis. We show that the countering effect of ghrelin on the
      LPS-induced acinar cell apoptosis was associated with the increase in
      constitutive nitric oxide synthase (cNOS) activity, and the reduction in caspase
      3 and inducible nitric oxide synthase (iNOS). The loss in countering effect of
      ghrelin on the LPS-induced changes in apoptosis and caspase-3 activity was
      attained with Src kinase inhibitor, PP2, as well as Akt inhibitor, SH-5, and cNOS
      inhibitor, L-NAME, but not the iNOS inhibitor, 1400W. The effect of ghrelin on
      the LPS-induced changes in cNOS activity, moreover, was reflected in the
      increased cNOS phosphorylation that was sensitive to PP2 as well as SH-5.
      Furthermore, the ghrelin-induced up-regulation in cNOS activity was associated
      with the increase in caspase-3 S-nitrosylation that was susceptible to the
      blockage by SH-5 and L-NAME. The findings point to the involvement of ghrelin in
      Src/Akt kinase-mediated cNOS activation and the apoptogenic signal inhibition
      through the NO-induced caspase-3 S-nitrosylation.

PMID- 20155329
TI  - Exploring factors that underlie racial/ethnic disparities in HIV risk among young
      men who have sex with men.
AB  - Young men who have sex with men (YMSM) are among the highest risk groups for HIV,
      and the risk distribution varies by race/ethnicity. Prevalence rates are
      consistently higher for minority YMSM. Factors underlying these disparities are
      poorly understood. We examined disparities in HIV risk among a community-based
      sample of Black, Latino, and non-Hispanic Caucasian YMSM age 16-24. To address
      gaps in the literature, we examined factors between and within racial/ethnic
      groups across domains including: sexual and substance use behaviors, sexualized
      and other social contexts, psychological well-being, HIV attributes and
      prevention skills, and sexual minority stress.

PMID- 20155330
TI  - Single port access (SPA) surgery--a 24-month experience.
AB  - INTRODUCTION: In April 2007, we performed our first single port access (SPA)
      surgical procedure. Beginning with simple procedures, we progressed to more
      complex procedures employing modifications of the initial technique. METHODS:
      Maintaining our abdominal entry technique through a single incision, typically
      umbilical, we have now successfully performed cholecystectomies, colon
      resections, small bowel procedures, liver biopsy, splenectomy, adrenalectomy, and
      surgery of the gastroesophageal junction. RESULTS: Two procedures have required
      additional port sites, none has employed transabdominal sutures, and <5% of all
      procedures have required articulation. Immediate follow-up demonstrates safe
      completion of multiple procedures with acceptable outcomes of blood loss and
      hospital stay. Although initial operative times are extended, a decrease is seen
      following a learning curve. At 2-year follow-up, two hernias developed at the
      extended incision for colon extraction. DISCUSSION AND CONCLUSION: With initial
      procedures performed in April 2007, we now report 24-month follow-up of a novel
      laparoscopic approach utilizing standard instrumentation. We demonstrate that SPA
      surgery is an alternative to multiport procedures with proposed initial benefits
      of decreased number of incisions and improved cosmesis for the patient. Long-term
      prospective randomized large case series will be necessary to assess pain,
      recovery, and hernia formation proving advantages, if any, over multiport
      laparoscopy.

PMID- 20155331
TI  - In utero exposure of female CD-1 mice to AZT and/or 3TC: II. Persistence of
      functional alterations in cardiac tissue.
AB  - To delineate temporal changes in the integrity and function of
      mitochondria/cardiomyocytes in hearts from mice exposed in utero to commonly used
      nucleoside analogs (NRTIs), CD-1 mice were exposed in utero to 80 mg AZT/kg, 40
      mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during days 12-18 of
      gestation and hearts from female mouse offspring were examined at 13 and 26 weeks
      postpartum. Alterations in cardiac mitochondrial DNA (mtDNA) content, oxidative
      phosphorylation (OXPHOS) enzyme activities, mtDNA mutations, and echocardiography
      of NRTI-exposed mice were assessed and compared with findings in vehicle-exposed
      control mice. A hybrid capture-chemiluminescence assay showed significant twofold
      increases in mtDNA levels in hearts from AZT- and AZT/3TC-exposed mice at 13 and
      26 weeks postpartum, consistent with near doubling in mitochondrial numbers over
      time compared with vehicle-exposed mice. Echocardiographic measurements at 13 and
      26 weeks postpartum indicated progressive thinning of the left ventricular
      posterior wall in NRTI-exposed mice, relative to controls, with differences
      becoming statistically significant by 26 weeks. Overall, progressive functional
      changes occurred in mouse mitochondria and cardiac tissue several months after in
      utero NRTI exposures; AZT and 3TC acted in concert to cause additive cardiotoxic
      effects of AZT/3TC compared with either drug alone.

PMID- 20155332
TI  - Neuronal vs. glial fate of embryonic stem cell-derived neural progenitors (ES
      NPs) is determined by FGF2/EGF during proliferation.
AB  - Fate-specific differentiation of neural progenitors attracts keen interest in
      modern medicine due to its application in cell replacement therapy. Though
      various signaling pathways are involved in maintenance and differentiation of
      neural progenitors, the mechanism of development of lineage-restricted
      progenitors from embryonic stem (ES) cells is not clearly understood. Here, we
      have demonstrated that neuronal vs. glial differentiation potential of ES cell
      derived neural progenitors (ES-NPs) are governed by the growth factors, exposed
      during their proliferation/expansion phase and cannot be significantly altered
      during differentiation phase. Exposure of ES-NPs to fibroblast growth factor-2
      (FGF2) during proliferation triggered the expression of pro-neural genes that are
      required for neuronal lineage commitment, and upon differentiation, predominantly
      generated neurons. On the other hand, epidermal growth factor (EGF)-exposed ES
      NPs are not committed to neuronal fate due to decreased expression of pro-neural
      genes. These ES-NPs further generate more glial cells due to expression of glial
      restricted factors. Exposure of ES-NPs to the same growth factors during
      proliferation/expansion and differentiation phase augments the robust
      differentiation of neurons or glial subtypes. We also demonstrate that, during
      differentiation, exposure to growth factors other than that in which the ES-NPs
      were expanded does not significantly alter the fate of ES-NPs. Thus, we conclude
      that FGF2 and EGF determine the neural vs. glial fate of ES-NPs during
      proliferation and augment it during differentiation. Further modification of
      these protocols would help in generating fate-specified neurons for various
      regenerative therapies.

PMID- 20155333
TI  - Limonoids from Dictamnus dasycarpus protect against glutamate-induced toxicity in
      primary cultured rat cortical cells.
AB  - In our previous report, four limonoids, obacunone, limonin, fraxinellone, and
      calodendrolide, isolated from Dictamnus dasycarpus showed significant
      neuroprotective activity against glutamate toxicity in primary cultured rat
      cortical cells. This study investigated neuroprotective mechanism of these
      compounds using the same in vitro culture system. These four compounds showed
      significant neuroprotective activity at the concentration of 0.1 muM. They
      effectively inhibited calcium influx and overproduction of cellular nitric oxide
      and reactive oxygen species accompanied by glutamate-induced neurotoxicity. In
      addition, these compounds significantly preserved mitochondrial membrane
      potential and activities of antioxidative enzymes. Our results showed that
      obacunone, limonin, fraxinellone, and calodendrolide significantly protect
      primary culture cortical cells against glutamate-induced toxicity by preserving
      the antioxidant defense system. These compounds might offer potential drug
      development candidate for various neurodegenerative diseases involved with
      glutamate.

PMID- 20155335
TI  - Analysis of super-low anterior resection for rectal cancer from a single center.
AB  - PURPOSE: The purpose of this study was to evaluate the outcome and genitourinary
      complications of super-low anterior resection (SLAR) followed by adjuvant
      radiochemotherapy in the management of patients with low rectal cancer. METHOD:
      One hundred and six low rectal cancer patients managed with SLAR were analyzed
      retrospectively. RESULTS: There were seven patients who failed to follow up, and
      the 5-year survival rate was 65.7% (65/99). There were 35 patients (35.4%) who
      developed distant metastases, and 12 (12.1%) had local recurrence. The local
      recurrence rates were 21.1% (4/19), 7.1% (2/28), 5.9% (1/17), and 0% (0/2) in the
      patients with tumor distance of less than or equal to 2 cm, ranging from 2.1 to
      3.0, from 3.1 to 4.0, from 4.1 to 5.0, and more than 5 cm, respectively. This
      implied local recurrence rate increased against the distance between the lower
      margin of tumor and resection line. Ninety-eight of 106 rectal patients had
      complete data of questionnaire: 58 scored 1, 32 scored 2, 7 scored 3, and 1 score
      4. This revealed that the fecal function of most patients (91.8%, 90/98) was
      normal or nearly normal. Twenty-four of 37 males suffered from sexual
      dysfunction, and among them, eight were impotent (all older than 70 years), and
      29 had retrograde ejaculation. Meanwhile, seven of 35 females suffered from
      sexual problem, 1 had dyspareunia, seven had decreased lubrication, and one had
      inability to achieve orgasm. CONCLUSIONS: SLAR followed by adjuvant
      radiochemotherapy can effectively control local-regional disease and can be one
      choice of avoiding the functional morbidity of abdominoperineal resection.

PMID- 20155334
TI  - Smad3 deficiency reduces neurogenesis in adult mice.
AB  - Transforming growth factor-beta signaling through Smad3 inhibits cell
      proliferation in many cell types. As cell proliferation in the brain is an
      integral part of neurogenesis, we sought to determine the role of Smad3 in adult
      neurogenesis through examining processes and structures important to neurogenesis
      in adult Smad3 null mice. We find that there are fewer proliferating cells in
      neurogenic regions of adult Smad3 null mouse brains and reduced migration of
      neuronal precursor cells from the subventricular zone to the olfactory bulb.
      Alterations in astrocyte number and distribution within the rostral migratory
      stream of Smad3 null mice give rise to a smaller and more disorganized structure
      that may impact on neuronal precursor cell migration. However, the proportion of
      proliferating cells that become neurons is similar in wild type and Smad3 null
      mice. Our results suggest that signaling through Smad3 is needed to maintain the
      rate of cell division of neuronal precursors in the adult brain and hence the
      amount of neurogenesis, without altering neuronal cell fate.

PMID- 20155337
TI  - Pluripotent stem cells as source of dendritic cells for immune therapy.
AB  - Dendritic cells (DC) are the most potent antigen-presenting cells. In vivo
      transfer of antigen-bearing DC has proven efficient in priming T cell responses
      specific to the antigen. DC-based cellular vaccination is now regarded as a
      powerful means for immunotherapy, especially for anti-cancer immunotherapy.
      Clinical trials of therapy with DC pulsed with peptide antigens or genetically
      modified to present antigens are currently carried out in many institutions. In
      addition, antigen-specific negative regulation of immune response by DC is
      considered to be a promising approach for treatments of autoimmune diseases and
      also for regulation of allo-reactive immune response causing graft rejection and
      GVHD in transplantation medicine. DC for transfer therapy are now generated by in
      vitro differentiation of peripheral blood monocytes of the patients. However,
      there is a limitation in the number of available monocytes, and the DC
      differentiation potential of monocytes varies depending on the blood donor.
      Embryonic stem (ES) cells possess both pluripotency and infinite propagation
      capacity. We consider ES cells to be an ideal source for DC to be used in
      immunotherapy. Several groups, including us, have developed methods to generate
      DC from ES cells. This review introduces the studies on generation,
      characterization, and genetic modification of DC derived from ES cells or induced
      pluripotent stem (iPS) cells. The issues to be resolved before clinical
      application of pluripotent stem cell-derived DC will also be discussed.

PMID- 20155338
TI  - Multicentric primary intestinal EBV-positive diffuse large B cell lymphoma of the
      elderly presenting with perforation.
AB  - Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) of the
      elderly is a recently defined subgroup of DLBCL in the 2008 WHO classification of
      lymphoid neoplasms. It is characterized by an EBV-positive clonal B cell
      lymphoproliferation that occurs in patients aged over 50 years without any known
      immunodeficiency. This disease shows frequent extranodal involvement, a
      morphological spectrum from polymorphous to monomorphic large cells, and a poor
      prognosis. We reported the case of a 75-year-old male who had a primary
      intestinal multicentric EBV(+) DLBCL and presented with perforation, the first
      multicentric case in the literature. The monomorphic tumor cells exhibited
      extensive necrosis and expressed CD20, CD138, and EBNA2 with diffuse positivity
      for EBV by in situ hybridization. Quantitative real-time PCR revealed a low serum
      EBV viral load. The patient passed away in 10 days. His poor outcome was probably
      due to perforation, age over 70, the presence of B symptoms, poor general
      condition, and high performance score.

PMID- 20155339
TI  - A case of treatment-related myelodysplastic syndrome spontaneously resolved by
      drug discontinuance.
AB  - Although great advancements have been witnessed in treatment results for
      hematopoietic tumors in recent years, development of secondary malignant tumors
      induced by anti-cancer drugs still remains a serious issue. We experienced a case
      of secondary myelodysplastic syndrome (MDS), possibly induced by cyclophosphamide
      (CY), which was spontaneously resolved by discontinuance of CY. A 24-year-old
      woman was diagnosed with follicular lymphoma in January 1998: she had developed
      bulky intra-abdominal lymphadenopathy, with repeated relapse and remission by
      several chemotherapy treatments. Remission was induced by rituximab, administered
      at the time of relapse in 2001, followed by administration of 50 mg/day of CY
      since December 2001 for the prevention of relapse. Anemia and thrombocytopenia
      developed around January 2003. Bone marrow aspiration revealed abnormality in two
      lineages and a complicated chromosomal anomaly, and the patient was diagnosed
      with MDS. Discontinuance of CY and administration of an anabolic steroid improved
      anemia and thrombocytopenia within 2 years. Bone marrow aspiration in 2006 showed
      improvement in morphological abnormality and disappearance of chromosomal
      abnormality.

PMID- 20155340
TI  - Surgical repair of pectus excavatum.
AB  - Pectus excavatum is the most common chest deformity. Children with severe
      deformities suffer physical complaints such as frequent respiratory infections
      and decreased endurance. Patients with even mild deformities may complain of
      physical and psychological symptoms after puberty. In most patients, cardiac and
      respiratory function deteriorates, meaning that surgical correction is important
      for alleviation of symptoms and improving cardiopulmonary function and quality of
      life. The methods of surgical repair remain controversial. The traditional
      method, first described by Ravitch, comprises resection of deformed cartilages
      and correction of the sternum by wedge osteotomy in the upper sternal cortex.
      Ravitch's methods have been modified using autologous or exogenous materials to
      fix the lower sternum. Nuss reported a novel method in which neither an anterior
      wound nor the cutting of cartilage or sternum is required; instead, a convex
      metal bar is placed behind the sternum. We have reported sternocostal elevation,
      in which a section of costal cartilage is resected, and all of the cartilage
      stumps are resutured to the sternum. The secured ribs pull the sternum
      bilaterally, such that the resultant force causes the sternum to rise anteriorly.
      Because most pectus excavatum patients are young and maintain an acceptable
      quality of life preoperatively, we believe that the morbidity rate is one of the
      most important factors in selecting the method for corrective surgery. Repair can
      be performed safely through the use of skilled techniques and a deep
      understanding of the anatomy and physiology of the thorax.

PMID- 20155341
TI  - Effect of opium use on short-term outcome in patients undergoing coronary artery
      bypass surgery.
AB  - PURPOSE: Data regarding the effect of opium use on short-term outcome in patients
      undergoing coronary artery bypass surgery are limited. We sought to assess the
      morbidity and in-hospital mortality of current and past users compared the data
      with those from nonusers of opium after coronary artery bypass grafting (CABG).
      METHODS: This is a descriptive analytical review of prospectively collected data
      on 782 consecutive male patients who underwent isolated CABG between January 2005
      and December 2007. Of these, 708 (90.5%) were nonusers, 56 (7.1%) were current
      users, and 18 (2.3%) were former opium users of more than 4 weeks. The effect of
      opium usage on clinical, admission, and outcome variables were analyzed. RESULTS:
      Current opium users were younger (P = 0.004) and more likely to be cigarette
      smokers (P = 0.0004). Other demographic characteristics, major coronary risk
      factors, rates of postoperative complications, intensive care unit readmission,
      postoperative length of stay, and in-hospital mortality did not differ among the
      three groups. Current opium users needed less analgesic postoperatively (P =
      0.0001), were significantly less compliant with medical and dietary
      recommendations after discharge (P < 0.0001), and were more likely to be
      rehospitalized with cardiovascular causes within 6 months after CABG surgery;
      these differences were much more pronounced for nonusers versus current users of
      opium (P < 0.0001). CONCLUSION: Continued use of opium is a significant predictor
      of rehospitalization with a cardiac cause within 6 months of CABG surgery. This
      may be partly due to the low compliance of these patients with treatment
      recommendations.

PMID- 20155342
TI  - New device for intraoperative graft assessment: HyperEye charge-coupled device
      camera system.
AB  - PURPOSE: Our institution developed a new color chargecoupled device (CCD) camera
      system (HyperEye system) for intraoperative indocyanine green (ICG) angiography.
      The device consists of a combination of custommade optical filters and an ultra
      high-sensitive CCD image sensor with non-Bayer color filter array (i.e., HyperEye
      technology), which can detect simultaneously color and near-infrared (NIR) rays
      from 380 to 1200 nm. Here, we demonstrate intraoperative graft assessment using
      the HyperEye system. METHODS: We investigated the intraoperative graft patency
      using both the HyperEye system and transittime flowmetry (TFM) in 51 patients
      between April 2007 and April 2009 while ICG dye was injected through a central
      venous catheter. Each patient signed a consent form before the surgery. RESULTS:
      We obtained intraoperative graft flows and images in 189 anastomoses of 153
      grafts. Both the HyperEye system and TFM indicated the patency of the grafts in
      129 grafts. Both the HyperEye system and TFM detected the abnormality of the
      graft in seven grafts. For the competitive flows, the HyperEye system captured to
      and-fro flow fluorescence and TFM detected the retrograde waveform in 16 grafts.
      On the other hand, although TFM indicated the patency of the graft, the HyperEye
      system suspected nonoccluded graft failure in seven grafts. In contrast, although
      TFM detected a mean flow of <10 ml/min, the HyperEye system captured the patent
      perfusion fluorescence in four grafts. CONCLUSION: The HyperEye system can
      visualize any structural and functional failures. Our findings suggest that this
      device could become a useful tool for intraoperative graft assessment.

PMID- 20155343
TI  - Giant aneurysm of the right coronary artery and fistula to the coronary sinus.
AB  - We describe the case of a 67-year-old man with a rare combination of a giant
      coronary artery aneurysm with a fistula draining into the coronary sinus. The
      patient presented with a sensation of retrosternal pressure. He was examined by
      coronary angiography, which revealed a large aneurysm of the right coronary
      artery (RCA) with a fistula. This fistula originated from the distal RCA shortly
      beyond the crux and drained into the coronary sinus. The aneurysm was in the
      proximal portion of the RCA, measuring 4 cm in diameter and 7 cm in length.
      Surgical repair by closure of the fistula under direct vision, suture closure and
      plication of the aneurysm, and coronary artery bypass was performed.
      Postoperative echocardiography and computed tomography confirmed closure of the
      fistula. The patient remains symptom-free at 4 months after surgery.

PMID- 20155344
TI  - Clinicopathological study of surgically treated cases of tracheobronchial adenoid
      cystic carcinoma.
AB  - Between 1980 and 2007, five patients were pathologically diagnosed as
      tracheobronchial adenoid cystic carcinoma (ACC). All five patients were women
      aged 37-67 years. Four tumors were located in the larger airways, and one tumor
      was located in the peripheral lung. The following operations were done:
      bronchoplastic procedures in three (carinal resection with doublebarreled
      carinoplasty in one, sleeve right pneumonectomy in one, sleeve middle lobectomy
      in one), left pneumonectomy in one, and left upper lobectomy in one. Three of the
      five patients have survived for 172, 144, and 10 months after surgery,
      respectively. The best local treatment for ACC of the major airway is considered
      to be sleeve resection of the trachea or bronchus in an area where airway
      reconstruction may not be disturbed and to add postoperative irradiation when
      there is residual carcinoma at the stump. However, it seems controversial to
      recommend adjuvant radiotherapy in all patients undergoing resection.

PMID- 20155345
TI  - Clear cell carcinoma of the lung.
AB  - We present here in the case of a patient who underwent resection of clear cell
      carcinoma of the lung, a rare histological type. A screening test of the 71-year
      old woman revealed a 2.0-cm lesion in S4 of the right lung with a diagnosis of
      bronchioloalveolar carcinoma before resection. Under the guidance of video
      assisted thoracoscopy, right middle lobe resection and mediastinal lymph node
      dissection were performed. The histopathological examination showed clear,
      slightly acidophilic tumor cells rich in fine granular components proliferating
      in an alveolar fashion. Immunostaining was diagnostically useful, distinguishing
      clear cell carcinoma from lung metastasis of renal clear cell carcinoma or clear
      cell squamous cell carcinoma.

PMID- 20155346
TI  - Minute localized malignant pleural mesothelioma coexisting with multiple
      adenocarcinomas.
AB  - We report an extremely rare case of minute localized malignant pleural
      mesothelioma (LMPM) coexisting with multiple lung adenocarcinomas in a 64-year
      old woman without a history of smoking or asbestos exposure. A computed
      tomography scan of the chest displayed total five ground-glass opacities in the
      lung. Transbronchial lung biopsy from a ground-glass opacity in the posterior
      segment revealed a bronchioloalveolar carcinoma. With a diagnosis of primary lung
      cancer, right upper lobectomy and wedge resection of the right lower lobe with
      systematic lymph node dissection was performed using video-assisted thoracoscopic
      surgery. Incidentally, a minute gray-white nodule measuring 6 mm was detected on
      the visceral pleural surface of the right upper lobe. The postoperative
      histological diagnosis was minute LMPM coexisting with multiple adenocarcinomas.

PMID- 20155347
TI  - Synovial sarcoma of the chest wall.
AB  - We here report a rare case of synovial sarcoma of the chest wall. A 71-year-old
      Japanese woman noticed a left anterior chest wall mass after twice having had
      surgery for lung cancer. An aspiration biopsy diagnosed synovial sarcoma. She
      then underwent a surgical resection. Pathology examination revealed a biphasic
      type synovial sarcoma. When the prepared RNA from the tumor was subjected to a
      polymerase chain reaction, SYT-SSX1 fusion gene transcripts were demonstrated.
      Patients with the SYT-SSX1 fusion gene have a worse clinical outcome than
      patients with SYT-SSX2-positive tumors. After a second surgery, performed in 1
      year later, there was no evidence of recurrence for 30 months; however, careful
      observation may be required.

PMID- 20155348
TI  - Thymic clear cell carcinoma.
AB  - We report a 42-year-old man with a rare thymic clear cell carcinoma. Marked nodal
      metastases involved right hilar, mediastinal, and left supraclavicular regions.
      Complete resection including thymothymectomy, cervicomediastinal nodal
      dissection, and right upper lobectomy with hilar lymphadenectomy was successful.
      Postoperative chemoradiation therapy was uneventful. The patient had no
      recurrence or metastasis until brain metastasis occurred 1 year after surgery.

PMID- 20155349
TI  - Excision of a left atrial myxoma in the presence of a calcified ascending aorta:
      a surgical challenge.
AB  - Atrial myxomas are rare tumors that require surgical excision. However, in the
      presence of a severely calcified ascending aorta, such excision becomes rather
      challenging and difficult. Here we report a case of a left atrial myxoma in a 64
      year-old woman with an extensively calcified aorta that was successfully excised
      using cardiopulmonary bypass beating-heart technique without the need for
      cardioplegic cardiac arrest and aortic cross-clamping. The use of this technique
      proved useful with no increased risk incurred to the patient.

PMID- 20155350
TI  - Mediastinal teratoma complicated with acute mediastinitis.
AB  - We report a case of a mediastinal teratoma associated with acute mediastinitis
      that required an emergency operation. These tumors cause a variety of
      complications, but reports of acute mediastinitis are rare. A 24-year-old woman
      was admitted to our hospital for complaints of chest pain and fever and was
      subsequently diagnosed as having an anterior mediastinal tumor. Follow-up
      computed tomography showed rapidly progressing acute mediastinitis, which was
      diagnosed as a perforation of the teratoma. We performed emergency surgical
      extirpation of the tumor and mediastinal drainage. The histopathologic diagnosis
      was a mature teratoma that included pancreatic tissue. Although the apparent site
      of the rupture was not obvious, there was a wide area of acute inflammation in
      the mediastinal adipose tissue. The patient did well and was discharged from the
      hospital without major complications.

PMID- 20155351
TI  - Esophageal patch tracheoplasty for congenital tracheal stenosis.

PMID- 20155352
TI  - Patients of surgical educational course may have a poorer outcome for pelvic
      organ prolapse repair and higher complication rate: a case-control study in
      urogynecology.
AB  - INTRODUCTION AND HYPOTHESIS: To investigate the outcome of the surgical
      educational course setting in patients undergoing urinary incontinence
      (UI)/pelvic organ prolapse (POP) repair. METHODS: A case-control study of
      patients who underwent surgery for UI and/or POP during educational post-graduate
      courses (group A) or during routine hospital work (control--group B). The primary
      outcome measures were changes in the incontinence rate, presence/absence of POP,
      and complications. For 2 x 2 tables, chi (2) test was used. Multivariate logistic
      regression models were developed. RESULTS: One hundred eighty-six patients
      belonged to group A and 158 to group B; median follow-up was 46.7 months.
      Failure, complication, and re-operation rates for UI repair were not
      significantly different in the two groups: p = 0.162, p = 0.110, p = 0.188,
      respectively. The logistic regression analysis for POP repair showed that group A
      has higher risk for failure (OR = 2.71; 95% CI: 1.31-5.61) and higher
      complication rate (OR = 2.38; 95% CI: 1.31-4.32). CONCLUSION: Patients who
      underwent surgery during educational course developed a poorer outcome after POP
      repair and higher complication rate.

PMID- 20155354
TI  - Optimization of phenazine-1-carboxylic acid production by a gacA/qscR-inactivated
      Pseudomonas sp. M18GQ harboring pME6032Phz using response surface methodology.
AB  - Phenazine-1-carboxylic acid (PCA) production was enhanced in Pseudomonas sp. M18
      wild strain and its mutants carrying recombinant pME6032Phz for phz gene cluster
      overexpression, among which Pseudomonas sp. strain M18GQ/pME6032Phz, a gacA and
      qscR double gene chromosomally inactivated mutant harboring pME6032Phz, showed
      the highest PCA yield. The conditions for fermentation and isopropyl-beta-D-1
      thiogalactopyranoside (IPTG) induction were optimized for strain M18GQ/pME6032Phz
      in shake flask experiments. A one-factor-at-a-time approach, followed by a
      fractional factorial design identified soybean meal, corn steep liquor, and
      ethanol as statistically significant factors. Optimal concentrations and mutual
      interactions of the factors were then determined by the method of steepest ascent
      and by response surface methodology based on the center composite design. The
      predicted PCA production was 6,335.2 mg/l after 60 h fermentation in the optimal
      medium of 65.02 g soybean meal, 15.36 g corn steep liquor, 12 g glucose, 21.70 ml
      ethanol, and 1 g MgSO(4) per liter in the flask fermentations, with induction of
      1.0 mmol/l IPTG 24 h after inoculation. In an experimental validation under these
      conditions, the maximum PCA production was 6,365.0 mg/l. This represents a
      approximately 60% increase over production by strain M18GQ in optimal conditions.
      The negative effect of plasmid pME6032 on the expression of chromosomally located
      phz gene cluster was found in Pseudomonas sp. M18GQ, and the possible reason was
      discussed in the text.

PMID- 20155355
TI  - Cloning, expression, and characterization of a thermostable glucoamylase from
      Thermoanaerobacter tengcongensis MB4.
AB  - A thermostable glucoamylase (TtcGA) from Thermoanaerobacter tengcongensis MB4 was
      successfully expressed in Escherichia coli. The full-length gene (2112 bp)
      encodes a 703-amino acid polypeptide including a predicted signal peptide of 21
      residues. The recombinant mature protein was partially purified to 30-fold
      homogeneity by heat treatment and gel filtration chromatography. The mature
      protein is a monomer with the molecular weight of 77 kD. The recombinant enzyme
      showed maximum activity at 75 degrees C and pH 5.0. It is the most thermostable
      bacterial glucoamylase described to date with nearly no activity loss after
      incubation at 75 degrees C for 6 h. TtcGA can hydrolyze both alpha-1, 4- and
      alpha-1, 6-glycosidic linkages in various alpha-glucans. It showed preference for
      maltooligosaccharides over polysaccharides with specific activity of 80 U/mg
      towards maltose. Kinetic studies revealed that TtcGA had the highest activity on
      maltooligosaccharide with four monosaccharide units. The cations Ca2+, Mn2+,
      Co2+, Mg2+, and reducing agent DTT showed no obvious effects on the action of
      TtcGA. In contrast, the enzyme was inactivated by Zn2+, Pb2+, Cu2+, and EDTA.

PMID- 20155356
TI  - Characterization of a Delta12-fatty acid desaturase gene from Ceriporiopsis
      subvermispora, a selective lignin-degrading fungus.
AB  - Ceriporiopsis subvermispora, a white-rot fungus, is characterized as one of the
      best biopulping fungi because it can degrade lignin selectively without serious
      damage to cellulose. We previously demonstrated that during the early stage of
      wood decay, this fungus produces large amounts of linoleic acid (18:2n-6) and
      degrades lignin by manganese peroxidase-catalyzed lipid peroxidation. In this
      study, we cloned a Delta12-fatty acid desaturase gene absolutely essential for
      the biosynthesis of linoleic acid as the main substrate for lipid peroxidation.
      This gene designated Cs-fad2 encodes a protein with three histidine-rich domains
      and four membrane-spanning domains characteristic of other Delta12-fatty acid
      desaturases. Moreover, we heterologously expressed Cs-fad2 in Saccharomyces
      cerevisiae lacking Delta12-fatty acid desaturase, and detected the de novo
      biosynthesis of linoleic acid by gas chromatography-mass spectrometry analysis.
      We also investigated transcription of Cs-fad2 under various conditions. The
      transcription was activated and repressed in the presence of a lignin fragment
      and exogenous fatty acids, respectively. These results may shed light on the
      molecular relationship between fatty acid metabolism and selective lignin
      degradation in C. subvermispora.

PMID- 20155353
TI  - MR plaque imaging of the carotid artery.
AB  - Atherosclerotic carotid plaque represents a major cause of cerebral ischemia. The
      detection of vulnerable plaque is important for preventing future cardiovascular
      events. The key factors in advanced plaque that are most likely to lead to
      patient complications are the condition of the fibrous cap, the size of the
      necrotic core and hemorrhage, and the extent of inflammatory activity within the
      plaque. Magnetic resonance (MR) imaging has excellent soft tissue contrast and
      can allow for a more accurate and objective estimation of carotid wall morphology
      and plaque composition. Recent advances in MR imaging techniques have permitted
      serial monitoring of atherosclerotic disease evolution and the identification of
      intraplaque risk factors for accelerated progression. The purpose of this review
      article is to review the current state of techniques of carotid wall MR imaging
      and the characterization of plaque components and surface morphology with MR
      imaging, and to describe the clinical practice of carotid wall MR imaging for the
      determination of treatment plan.

PMID- 20155357
TI  - Is 3T-MR spectroscopy a predictable selection tool in prophylactic
      vertebroplasty?
AB  - This study was designed to confirm relationships between decrease of bone mineral
      density and increase of marrow fat and to delineate, through MR spectroscopy,
      vertebral body at high risk for compression fracture onset to justify
      prophylactic vertebroplasty. We enrolled 127 women: 48 osteoporotic, 36
      osteopenic, and 43 normal subjects, who underwent DXA and MR examination of
      spine. Then, we selected 48 patients with at least two acute osteoporotic
      vertebral fractures with interposed normal "sandwich" vertebrae; all patients
      underwent MR examination of spine. Significant statistical differences were found
      among "Fat Fraction" (FF) values in normal, osteopenic, and osteoporotic
      subjects: 59.8 +/- 5.1%; 64.8 +/- 4.4%; and 67.1 +/- 3.3%. A mild, significant,
      negative correlation was observed between T-score and vertebral fat content (r = 
      0.585; P = 0.0000). In the second part of the study, 9 new vertebral fractures
      were observed in 48 patients (19%): 6 were "sandwich" vertebrae (12.5%), and 3
      were located in distant vertebral body. The mean FF in sandwich fractured
      vertebrae was 72.75 +/- 1.95 compared with the FF of the nonfractured sandwich,
      and distant control vertebrae were 61.83 +/- 3.42 and 61.42 +/- 3.64. We found a
      significant statistical difference between fractured and nonfractured vertebrae
      (P < 0.001). The results of this study suggest that MR spectroscopy could be a
      reliable index to predict the risk of new compression vertebral fracture and
      could be used for vertebroplasty planning contributing to clarify the possibility
      to add prophylactic PVP to standard treatment.

PMID- 20155358
TI  - Bioaccumulation and biovolatilisation of pentavalent arsenic by Penicillin
      janthinellum, Fusarium oxysporum and Trichoderma asperellum under laboratory
      conditions.
AB  - Some fungi are able to control and remediate arsenic (As)-contaminated soil,
      sediment, or water. Here, we investigate potential accumulation and
      volatilisation of As by three fungi strains. Results indicated that the highest
      level of As was accumulated by Penicillin janthinellum with 39.54 MUg after 10
      days in the culture system amended with 2,500 MUg As(V), which represents 50 mg/l
      As. Fusarium oxysporum showed the highest amount of volatilised As with 304.06
      MUg after 15 days. The As content in the treated system (filter paper + As +
      fungi) was significantly higher than that in the control (filter paper + As;
      filter paper + fungi; filter paper). Trichoderma asperellum and F. oxysporum
      showed superior abilities for the absorption of extracellular As and accumulation
      of intracellular As, which accounted for 82.2 and 63.4% of the total accumulated
      As, respectively. However, P. janthinellum presented an equal distribution of
      intracellular and extracellular As. Scanning electron microscope (SEM) analysis
      suggested that little impact on mycelium growth of the three fungal strains was
      seen after exposure to 50 mg/l As(V) for 5 days, while the growth of fungi in the
      control was inhibited. The present results demonstrate that P. janthinellum, F.
      oxysporum, and T. asperellum would be expected to tackle As-contaminated
      environments.

PMID- 20155359
TI  - Prospective, randomized, controlled clinical trial of Ankaferd Blood Stopper in
      patients with acute anterior epistaxis.
AB  - This is a study evaluating the efficacy of Ankaferd Blood Stopper (ABS) as a
      hemostatic agent compared to hemostasis by phenylephrine in patients with
      anterior epistaxis. The study design is a prospective, randomized, controlled,
      nonblinded, clinical trial. In total, 49 patients were randomly seperated to
      receive hemostasis technique by means of either ABS wet tampon or phenylephrine
      impregnated gauze tampon for anterior epistaxis control. Patients were crossed
      over to the other technique after two unsuccessful attempts of the first
      technique. Measured outcomes such as number of applications, relationship of
      number of applications with bleeding intensity (1 = stains on napkin, 2 = soaked
      napkin, 3 = bowl needed), patient discomfort during hemostasis (0 = none, 9 =
      unbearable), and complications were assessed. Additional data were recorded for
      rebleeding within 7 days. 24 of the 49 patients were assigned to the new ABS
      group (group I) and remaining 25 were included in the standard phenylephrine
      group (group II). ABS was more effective than phenylephrine at control of
      anterior epistaxis (79.2 vs. 64%, p < 0.05). For the patients who crossed over
      from phenylephrine to ABS, 44.4% achieved hemostasis by ABS. ABS successfully
      treated all bleeding intensity 1 and 2 patients with one application (5 min). ABS
      patients experienced fewer rebleeding rates within 7 days compared to
      phenylephrine patients (8.3 vs. 20%, p < 0.05). The patients for which ABS was
      applied, significant differences in effective control of anterior epistaxis were
      observed compared to phenylephrine. ABS is effective, safe, quick, and easy
      alternative to the phenylephrine in patients with anterior epistaxis.

PMID- 20155360
TI  - Thyroid incidentalomas: to treat or not to treat.
AB  - Incidental lesions of the thyroid gland are an increasing problem facing
      clinicians. While asymptomatic palpable lesions are detected in only 4-7% of the
      population, currently available imaging modalities are sensitive enough to detect
      lesions in 20-30% of the population. Guidelines for managing these incidentalomas
      are limited, largely due to lack of well-powered prospective studies. This review
      will address the currently available data on thyroid incidentalomas, detected
      through clinical examination, cross-sectional imaging, ultrasound, and PET scans.
      We will focus on the modalities of detection and risk of malignancy, further
      investigation and management options and the deficiencies therein. We propose a
      pragmatic algorithm when faced with this clinical dilemma under differing
      circumstances.

PMID- 20155362
TI  - Is the word 'biomarker' being properly used by proteomics research in
      neuroscience?

PMID- 20155361
TI  - Contemporary management of cancer of the oral cavity.
AB  - Oral cancer represents a common entity comprising a third of all head and neck
      malignant tumors. The options for curative treatment of oral cavity cancer have
      not changed significantly in the last three decades; however, the work up, the
      approach to surveillance, and the options for reconstruction have evolved
      significantly. Because of the profound functional and cosmetic importance of the
      oral cavity, management of oral cavity cancers requires a thorough understanding
      of disease progression, approaches to management and options for reconstruction.
      The purpose of this review is to discuss the most current management options for
      oral cavity cancers.

PMID- 20155363
TI  - Antiangiogenic mechanisms of simvastatin in retinal endothelial cells.
AB  - BACKGROUND: While statins have an anti-angiogenic property, their underlying
      mechanisms are not fully understood. We investigated intracellular mechanisms of
      simvastatin-mediated reduction in VEGF-induced signalings. METHODS: The effects
      of simvastatin on cell proliferation and viability were evaluated by [(3)H]
      thymidine incorporation in retinal endothelial cells (RECs) and cell counting.
      The impact of simvastatin on VEGF-induced phosphorylation of p44/42 mitogen
      activated protein (MAP) kinase, myosin light chain (MLC), and VEGF-receptor
      (VEGFR) 2 were examined by Western blotting. Involvement of the mevalonate
      pathway in VEGF-induced signaling was also examined. RESULTS: Simvastatin (1 and
      10 microM) suppressed VEGF-induced RECs proliferation in a concentration
      dependent manner, without affecting cell viability. Simvastatin significantly
      inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream mediators,
      p44/42 MAP kinase and MLC. Mevalonate completely reversed VEGF-induced VEGFR2
      phosphorylation, but only partially reversed the phosphorylation of p44/42 MAP
      kinase and MLC. CONCLUSION: These data indicate that simvastatin exerts its anti
      angiogenic effects through the reduction of VEGFR2 phosphorylation in RECs at
      least in part. However, there seems to be both mevalonate-dependent and
      independent pathway in simvastatin's anti-angiogenic property.

PMID- 20155364
TI  - Impact of gentamicin-supplemented polyvinylidenfluoride mesh materials on MMP-2
      expression and tissue integration in a transgenic mice model.
AB  - PURPOSE: Reinforcement of the abdominal wall by alloplastic mesh material results
      in a chronic foreign body reaction which is characterized by a transcriptionally
      induced overexpression of the matrix metalloproteinases-2 (MMP-2). Mesh
      modification represents a new approach to normalize the MMP-2 expression and
      thereby to reduce the foreign body reaction. Because of its proven beneficial
      effect on tissue integration, the influence of gentamicin-supplemented
      polyvinylidenfluoride (PVDF) mesh materials on MMP-2 transcription and protein
      expression was investigated in transgenic reporter mice harboring MMP-2
      regulatory sequence-1686/+423. METHODS: A PVDF mesh material was surface-modified
      by plasma-induced graft polymerization of acrylic acid (PVDF + PAAc). Three
      different gentamicin concentrations were bound to the provided active sites of
      the grafted mesh surfaces (2, 5, and 8 microg/mg). Seventy-five male transgenic
      MMP-2/LacZ CD1-tg mice harboring MMP-2 regulatory sequences -1686/+423 were
      randomized to five groups. Bilateral of the abdominal midline, one of the five
      different meshes was implanted subcutaneously in each animal. MMP-2 gene
      transcription and protein expression were analyzed semiquantitatively 7, 21, and
      90 days after mesh implantation. The collagen type I/III ratio was analyzed by
      cross-polarization microscopy to determine the quality of mesh integration.
      RESULTS: The perifilamentary MMP-2 protein expression as well as the MMP-2
      promoter activity decreased over time, whereas the collagen type I/III ratio
      increased up to the 90th day for all mesh modifications. The 8-microg/mg mesh
      material showed significantly reduced levels of MMP-2-positive stained cells when
      compared with the PVDF group on days 7, 21, and 90 (p = 0.008; p = 0.016; p =
      0.016). In accordance, the 8-microg/mg group revealed a significant reduction of
      beta-galactosidase-positive stained cells at each time point in comparison with
      the PVDF group (p = 0.008; p = 0.047; p = 0.016). Though the type I/III collagen
      ratio increased over time for all mesh modifications significant differences to
      the PVDF mesh could only detected for 8-microg/mg group (p = 0.008; p = 0.032; p
      = 0.016). CONCLUSIONS: Our results show a dose-dependent effect of gentamicin.
      The reduced MMP-2 protein expression and transcription after mesh coating with 8
      microg/mg gentamicin together with the improved collagen type I/III hint on an
      advanced tissue integration even in the long-term. Subsequent studies are needed
      to elucidate interaction of collagen and MMP-2 in chronic foreign body reaction.

PMID- 20155365
TI  - Neutrophil phenotype and function in partial hepatectomy in man.
AB  - PURPOSE: Hepatic resections are still associated with considerable morbidity
      mainly because of postoperative infection. Adequate function of neutrophils is a
      crucial element in host defense. The aim of the study was to characterize
      neutrophils during partial hepatectomy. METHODS: Fourteen patients undergoing
      partial liver resection were enrolled. Twenty-four hours pre-, intra- (after
      induction of anesthesia, after preparation of the liver, and 15 min after release
      of the Pringle maneuver), as well as postoperatively (3 h after Pringle; 24, 48,
      and 120 h after surgery), blood samples were obtained. In addition, healthy
      volunteers (n = 5) were investigated. Adhesion molecules (CD 62, CD 18), Fcy
      receptors (CD 16, CD 32), and phagocytosis by neutrophils were characterized by
      fluorescence-activated cell sorter analysis. Spontaneous and stimulated (formyl
      methionyl-leucyl-phenylalanine) oxygen radical generation was measured by
      lucigenin-enhanced chemiluminescence. RESULTS: Numeric upregulation of CD 62 and
      CD 18 on neutrophils was seen before the use of Pringle maneuver and persisted
      thereafter (p < 0.05). Spontaneous numeric expression of Fcy receptors (CD16 and
      CD 32) was unchanged during liver dissection but downregulated after Pringle
      maneuver was opened (p < 0.05). Although numeric Fcy receptors were
      downregulated, phagocytosis of heterologous opsonized Escherichia coli bacteria
      by neutrophils was unaffected. Spontaneous oxygen radical production peaked
      sharply 15 min after release of the Pringle maneuver (p < 0.05), contrary to
      stimulated oxygen radical production, which was depressed 3 h after the release
      of the Pringle maneuver (ns). CONCLUSIONS: Uneventful partial hepatectomy in man
      resulted already in a significant change in the phenotype but in less significant
      changes in the functions of neutrophils.

PMID- 20155366
TI  - Activation of protective cell-mediated immune response in gastric mucosa during
      Cryptosporidium muris infection and re-infection in immunocompetent mice.
AB  - Gastric cryptosporidia only inhabit the glandular part of the stomach of all age
      categories of their hosts and can cause chronic life-long infections independent
      of a host's immune status. The immune response in the stomach mucosa during the
      primary infection and re-infection with Cryptosporidium muris (TS03 and CB03) in
      immunocompetent BALB/c mice was characterized using flow cytometry analysis and
      measurement of IFN-gamma and IL10 by enzyme-linked immunosorbent assays (ELISA).
      Significantly, elevated migration of T lymphocytes (more than 1,000-fold),
      especially CD8+ T lymphocytes, to the stomach mucosa occurred during primary
      infection and persisted for more than 2 months after its resolution. The ex vivo
      cultures of splenocytes revealed very low levels of IFN-gamma production during
      the course of the primary infection (0.5 ng/ml), whereas in the following re
      exposure to the parasites, the concentration of IFN-gamma rapidly increased 22
      fold. Although the two parasite strains that were tested were genetically
      distinct, they yielded similar results in the induction of cellular immune
      responses, suggesting that these patterns are not unique to a single parasite
      strain. These results imply that the CD8+ T lymphocytes are involved in the
      immune response to gastric cryptosporidiosis and could play an important role in
      the elimination of C. muris infection in mice.

PMID- 20155367
TI  - Application of the SYBR Green real-time HRM PCR technique in the differentiation
      of the Babesia canis canis protozoa isolated in the areas of eastern Poland.
AB  - The aim of this study was to determine the usefulness of the real-time
      polymerised chain reaction (PCR) high-resolution melting (HRM) method in the
      differentiation of the Babesia canis canis protozoa isolated from dogs in the
      areas of eastern Poland. The studies involved 20 isolates of B. canis canis
      qualified depending on the analysis of the 18S RNA gene sequence to group A (EU
      622792) and 20 isolates qualified to group B (EU 622793). It was proven with the
      real-time PCR technique that the melting temperature (Tm) of the obtained
      products of amplification was 78 degrees C for the representatives of group A and
      81 degrees C for the representatives of group B, which proves that the real-time
      SYBR Green HRM PCR method is a technique allowing for the differentiation of the
      B. canis isolates which are slightly different with respect to the genetic
      structure, without the necessity to carry out time-consuming studies, i.e.,
      sequencing and restriction fragment length polymorphism.

PMID- 20155368
TI  - Absence of ivermectin resistance in a survey on dairy goat nematodes in France.
AB  - Anthelmintic resistance is very prevalent in ruminant strongyle populations,
      especially in goats. Several occurrences of multiple anthelminthic resistances
      have been reported in goat flocks throughout the world, including resistance to
      the most recent macrocyclic lactones. A faecal egg count reduction test was
      conducted to detect resistance to ivermectin in French goat flocks. Thirty goats
      per flock were randomly selected in 22 flocks and allocated into two groups of 15
      animals: an untreated control group and an ivermectin-treated group (0.3 mg/kg BW
      per os). Individual faecal egg counts and pooled larval cultures were performed
      16-17 days after anthelmintic treatment for control and treated groups. FECR's
      were calculated for treated group vs. control one and when <95/100, were
      considered as indicative of anthelmintic resistance. FECR results indicated the
      absence of ivermectin resistance in nematode populations from all the 22 goat
      farms. The nematode genera involved in control groups were of
      Teladorsagia/Trichostrongylus, Haemonchus and Oesophagostomum/Chabertia types.

PMID- 20155369
TI  - Climate change and threat of vector-borne diseases in India: are we prepared?
AB  - It is unequivocal that climate change is happening and is likely to expand the
      geographical distribution of several vector-borne diseases, including malaria and
      dengue etc. to higher altitudes and latitudes. India is endemic for six major
      vector-borne diseases (VBD) namely malaria, dengue, chikungunya, filariasis,
      Japanese encephalitis and visceral leishmaniasis. Over the years, there has been
      reduction in the incidence of almost all the diseases except chikungunya which
      has re-emerged since 2005. The upcoming issue of climate change has surfaced as a
      new threat and challenge for ongoing efforts to contain vector-borne diseases.
      There is greater awareness about the potential impacts of climate change on VBDs
      in India and research institutions and national authorities have initiated
      actions to assess the impacts. Studies undertaken in India on malaria in the
      context of climate change impact reveal that transmission windows in Punjab,
      Haryana, Jammu and Kashmir and north-eastern states are likely to extend
      temporally by 2-3 months and in Orissa, Andhra Pradesh and Tamil Nadu there may
      be reduction in transmission windows. Using PRECIS model (driven by HadRM2) at
      the resolution of 50 x 50 Km for daily temperature and relative humidity for year
      2050, it was found that Orissa, West Bengal and southern parts of Assam will
      still remain malarious and transmission windows will open up in Himachal Pradesh
      and north-eastern states etc. Impact of climate change on dengue also reveals
      increase in transmission with 2 C rise in temperature in northern India. Re
      emergence of kala-azar in northern parts of India and reappearance of chikungunya
      mainly in southern states of India has also been discussed. The possible need to
      address the threat and efforts made in India have also been highlighted. The
      paper concludes with a positive lead that with better preparedness threat of
      climate change on vector-borne diseases may be negated.

PMID- 20155370
TI  - A survey of the prevalence and genotypes of Giardia duodenalis infecting
      household and sheltered dogs.
AB  - Giardia duodenalis (syn. G. intestinalis, G. lamblia) is an intestinal protozoan
      parasite that infects humans and a wide range of mammals that includes dogs.
      Highly significant genetic heterogeneity has been found within this species,
      while only genotypes from assemblages A and B have zoonotic potential. Although
      Giardia infection in dogs has been reported worldwide, there is increasing
      molecular evidence that dogs may be infected with host-specific genotypes (C and
      D) as well as zoonotic ones (A and B). Therefore, dogs play a role as a potential
      source of Giardia infection impacting humans and other Canidae. Fecal samples
      from privately owned dogs and from dogs kept in two shelters in the west-central
      region of Poland were examined using a microscope and polymerase chain reaction.
      The total prevalence of Giardia in specimens was 1.9%. Deoxyribonucleic acid was
      extracted only from two out of the three Giardia-positive fecal samples. After
      amplification using the G7 and G759 beta-giardin primers, 753 bp amplicons were
      obtained, and both amplification products were sequenced. Sequence and
      phylogenetic analyses showed that both G. duodenalis isolates were dog-specific
      genotypes (C and D).

PMID- 20155371
TI  - Mosquito distribution and Japanese encephalitis virus infection in the
      immigration bird (Asian open-billed stork) nested area in Pathum Thani province,
      central Thailand.
AB  - Japanese encephalitis virus infection is a mosquito-borne emerging or re-emerging
      infectious disease in several countries. The ecology of this virus in nature
      includes amplifying avian or mammal hosts and mosquito vectors. Infected
      immigration birds from epidemic areas may play important roles in the outbreak of
      the disease. The prevalence is high during the raining season in Thailand and
      human cases have been reported from several provinces including Bangkok suburbs.
      This study was conducted to investigate the mosquito distribution and Japanese
      encephalitis virus infection in the immigration bird (Asian open-billed stork)
      nested area, Pathum Thani province, central Thailand. Mosquitoes were collected
      by using CO(2)-baited Centers for disease control and prevention (CDC) light
      traps, and dry ice was used as a source of CO(2) to attract mosquitoes from March
      2008 to January 2009. Eight traps were operated from 4 p.m. until 7 a.m. on each
      study day. There were seven genera collected: Aedes, Anopheles, Armigeres,
      Coquillettidia, Culex, Mansonia, and Uranotaenia. Culex tritaeniorhynchus was the
      most collected species in each month, except November, in which Culex gelidus was
      the most collected species. Sixty pools of C. gelidus and of C.
      tritaeniorhynchus, each of which had 50 mosquitoes, were tested for Japanese
      encephalitis virus infection by using reverse transcription polymerase chain
      reactions; however, none of them was infected with the virus.

PMID- 20155372
TI  - The effect of tribendimidine and its metabolites against Necator americanus in
      golden hamsters and Nippostrongylus braziliensis in rats.
AB  - The antinematode effect of tribendimidine (TBD) and its metabolites has been
      studied. A total of 107 hamsters were each infected with 250 Necator americanus
      third stage infective larvae (NaL3) for 25 days. In the first test, 75 hamsters
      were divided equally into 15 groups for determination of ED(50) and ED(90.) Among
      them, five groups were treated orally with TBD or its metabolite, p-(1
      dimethylamino ethylimino)aniline (aminoamidine, deacylated amidantel, BAY d 9216,
      dADT), at single doses of 1, 2, 4, 8, and 16 mg/kg. The remaining five groups
      were administered with acetylated dADT (AdADT) at single oral doses of 8, 12, 18,
      24, and 30 mg/kg. In the second test, 20 hamsters were equally divided into four
      groups. Two groups were treated intramuscularly with TBD and dADT at a single
      dose of 16 mg/kg, while in the remaining two groups, single intramuscular dose of
      AdADT 15 or 30 mg/kg was administered. In the third test, two groups of six
      hamsters were treated orally with terephthalaldehyde (TPAL) and terephthalic acid
      (TPAC) at a single dose of 1,000 mg/kg. Other 85 rats, each infected with 300
      Nippostrongylus braziliensis third stage infective larvae (NbL3), were used in
      three tests. For determination of ED(50) and ED(90) in the first test, five
      groups of five rats were treated orally with TBD or dADT at single doses of 3.0,
      4.2, 5.9, 8.2, and 11.5 mg/kg or 2.0, 2.9, 4.2, 6.1, and 8.8 mg/kg, respectively.
      In the second test, three groups of eight to nine rats were treated orally with
      TBD at a single 8.4-mg/kg dose (ED(90)) and AdADT 100 or 200 mg/kg, respectively.
      In the third test, two groups of four rats were treated orally with TPAL and TPAC
      at a single dose of 1,000 mg/kg. Twenty-four to 48 h post-treatment, all the
      feces of each hamster and rat were collected for recovery of worms expelled from
      the feces. Following this period, all of the animals were sacrificed, and the
      adult hookworm or N. braziliensis from small intestine and large intestine were
      recovered and counted for calculation of worm burden reduction. The results
      showed that the ED(50) and ED(90) for TBD, dADT, and AdADT determined in
      treatment of N. americanus-infected hamsters were 1.849 and 13.598, 3.922 and
      54.354, as well as 20.966 and 51.633 mg/kg, respectively. In intramuscular
      administration of TBD and dADT at single dose of 16 mg/kg or AdADT 30 mg/kg,
      similar worm burden reductions of 71.4-76.3% were observed. Two other
      metabolites, i.e., TPAL and TPAC, exhibited no effect against N. americanus. The
      ED(50) and ED(90) for TBD and dADT determined in treatment of rats infected with
      N. braziliensis were 3.234 and 8.435, as well as 2.345 and 5.104 mg/kg. Oral
      administration of AdADT at a higher single dose of 100 or 200 mg/kg resulted in
      worm burden reductions of 11.9-46.3%, which was significantly lower than 84.5% of
      worm burden reduction obtained from rats treated with TBD 8.4 mg/kg. The results
      indicate that in oral administration, TBD exhibits slightly better effect against
      N. americanus in hamsters than dADT, but AdADT possesses less effect; TBD, dADT,
      and AdADT show promising effect in intramuscular treatment of N. americanus
      infected hamsters; the effect of oral dADT against N. braziliensis in rats is
      somewhat better than TBD, while AdADT endorses poor effect; and TPAL and TPAC are
      ineffective metabolites of TBD against both species of nematodes.

PMID- 20155373
TI  - Identification of the nucleoli of Giardia lamblia with TEM and CFM.
AB  - Giardia species are flagellated parasites of vertebrates and belong to the
      diplomonads, most of which have two nuclei. These organisms were classified among
      the earliest branching eukaryotes on the basis of small subunit rDNA sequences
      and their lack of many canonical organelles. However, some of these organelles
      have subsequently been identified in rudimentary form, such as Golgi that become
      apparent during encystation. One of the "missing" organelles has been the
      nucleolus, the site of rRNA synthesis, since it was not identified in earlier
      ultrastructural studies. In the current study, we visualized in-vitro-grown
      Giardia lamblia trophozoites by transmission electron microscopy and laser
      scanning confocal microscopy. We found that each of the two nuclei contains a
      single small and deeply stained granular nucleolus, thus demonstrating that
      Giardia does indeed have nucleoli.

PMID- 20155374
TI  - Leaf litter traits of invasive species slow down decomposition compared to
      Spanish natives: a broad phylogenetic comparison.
AB  - Leaf traits related to the performance of invasive alien species can influence
      nutrient cycling through litter decomposition. However, there is no consensus yet
      about whether there are consistent differences in functional leaf traits between
      invasive and native species that also manifest themselves through their "after
      life" effects on litter decomposition. When addressing this question it is
      important to avoid confounding effects of other plant traits related to early
      phylogenetic divergences and to understand the mechanism underlying the observed
      results to predict which invasive species will exert larger effects on nutrient
      cycling. We compared initial leaf litter traits, and their effect on
      decomposability as tested in standardized incubations, in 19 invasive-native
      pairs of co-familial species from Spain. They included 12 woody and seven
      herbaceous alien species representative of the Spanish invasive flora. The
      predictive power of leaf litter decomposition rates followed the order: growth
      form > family > status (invasive vs. native) > leaf type. Within species pairs
      litter decomposition tended to be slower and more dependent on N and P in
      invaders than in natives. This difference was likely driven by the higher lignin
      content of invader leaves. Although our study has the limitation of not
      representing the natural conditions from each invaded community, it suggests a
      potential slowing down of the nutrient cycle at ecosystem scale upon invasion.

PMID- 20155376
TI  - Adiponectin deficiency enhanced the severity of cerulein-induced chronic
      pancreatitis in mice.
AB  - BACKGROUND: Adiponectin is recognized as an antiinflammatory and antifibrotic
      protein derived from adipocytes, and low serum adiponectin levels are present in
      obesity. Recent studies have highlighted the relationship between obesity and
      pancreatic diseases. However, the role of adiponectin in chronic pancreatitis
      remains uncertain. The aim of this study was to determine the effects of
      adiponectin in chronic pancreatitis. METHODS: We investigated the effects of
      adiponectin in experimental chronic pancreatitis by using adiponectin-knockout
      (APN-KO) mice. Chronic pancreatitis was induced by repeated hourly (6 times)
      intraperitoneal injections of 50 microg/kg cerulein three times per week for 4
      weeks in wild-type (WT) and APN-KO mice. We evaluated the severity of chronic
      pancreatitis biochemically and morphologically. RESULTS: In cerulein-treated
      mice, macroscopically and histologically, severe pancreatic damage was observed
      in APN-KO mice compared with findings in WT mice. The histological scores for
      chronic pancreatitis, including glandular atrophy, pseudotubular complex,
      fibrosis, and total scores, were significantly higher in APN-KO mice than in WT
      mice. Activated pancreatic stellate cells and F4/80-positive pancreatic
      macrophages accumulated in the pancreas of APN-KO mice but not in WT mice.
      Overexpression of the mRNAs of transforming growth factor-beta1, CD68, and
      monocyte chemoattractant protein-1 was noted in APN-KO mice but not in WT mice.
      The gene expression level of collagen1 (alpha1) tended to be higher in APN-KO
      mice than in WT mice, albeit insignificantly. CONCLUSIONS: Adiponectin deficiency
      enhanced the severity of cerulein-induced chronic pancreatitis in mice.
      Hypoadiponectinemia could enhance the severity of chronic pancreatitis.

PMID- 20155377
TI  - Ectomycorrhizal community structure of different genotypes of Scots pine under
      forest nursery conditions.
AB  - In this paper, we report the effect of Scots pine genotypes on ectomycorrhizal
      (ECM) community and growth, survival, and foliar nutrient composition of 2-year
      old seedlings grown in forest bare-root nursery conditions in Lithuania. The
      Scots pine seeds originated from five stands from Latvia (P1), Lithuania (P2 and
      P3), Belarus (P4), and Poland (P5). Based on molecular identification, seven ECM
      fungal taxa were identified: Suillus luteus and Suillus variegatus (within the
      Suilloid type), Wilcoxina mikolae, Tuber sp., Thelephora terrestris, Cenococcum
      geophilum, and Russuloid type. The fungal species richness varied between five
      and seven morphotypes, depending on seed origin. The average species richness and
      relative abundance of most ECM morphotypes differed significantly depending on
      pine origin. The most essential finding of our study is the shift in dominance
      from an ascomycetous fungus like W. mikolae in P2 and P4 seedlings to
      basidiomycetous Suilloid species like S. luteus and S. variegatus in P1 and P5
      seedlings. Significant differences between Scots pine origin were also found in
      seedling height, root dry weight, survival, and concentration of C, K, Ca, and Mg
      in the needles. The Spearman rank correlation coefficient revealed that survival
      and nutritional status of pine seedlings were positively correlated with
      abundance of Suilloid mycorrhizas and negatively linked with W. mikolae
      abundance. However, stepwise multiple regression analysis showed that only
      survival and magnesium content in pine needles were significantly correlated with
      abundance of ECM fungi, and Suilloid mycorrhizas were a main significant
      predictor. Our results may have implications for understanding the physiological
      and genetic relationship between the host tree and fungi and should be considered
      in management decisions in forestry and ECM fungus inoculation programs.

PMID- 20155379
TI  - Myocardial MIBG scintigraphy: a useful clinical tool? : A retrospective study in
      50 parkinsonian patients.
AB  - Meta-iodbenzylguanidine scintigraphy (MIBG scintigraphy) shows reduced uptake in
      idiopathic Parkinson's disease (IPD), idiopathic REM sleep behavior disorder
      (IRBD) and Lewy body dementia (LBD), but not in other parkinsonian or dementia
      syndromes. We retrospectively reevaluated 50 patients. Concordance rate between
      last clinical diagnosis and scintigraphy diagnosis was only given in two-thirds
      of the patients. Confounding factors were: decreasing heart/mediastinum ratio
      (HMR) with progressive age, higher HMR in women and possibly interference with
      antihypertensive medication. Standardization of the methods and precise clinical
      guidelines are warranted for better clinical use.

PMID- 20155378
TI  - Oligonucleotides are potent antioxidants acting primarily through metal ion
      chelation.
AB  - We report on a rather unknown feature of oligonucleotides, namely, their potent
      antioxidant activity. Previously, we showed that nucleotides are potent
      antioxidants in Fe(II)/Cu(I/II)-H(2)O(2) systems. Here, we explored the potential
      of 2'-deoxyoligonucleotides as inhibitors of the Fe(II)/Cu(I/II)-induced *OH
      formation from H(2)O(2). The oligonucleotides [d(A)(5,7,20); d(T)(20); (2'-OMe
      A)(5)] proved to be highly potent antioxidants with IC(50) values of 5-17 or 48
      85 microM in inhibiting Fe(II)/Cu(I)- or Cu(II)-induced H(2)O(2) decomposition,
      respectively, thus representing a 40-215-fold increase in potency as compared
      with Trolox, a standard antioxidant. The antioxidant activity is only weakly
      dependent on the oligonucleotides' length or base identity. We analyzed by matrix
      assisted laser desorption/ionization time of flight mass spectrometry and (1)H
      NMR spectroscopy the composition of the d(A)(5) solution exposed to the
      aforementioned oxidative conditions for 4 min or 24 h. We concluded that the
      primary (rapid) inhibition mechanism by oligonucleotides is metal ion chelation
      and the secondary (slow) mechanism is radical scavenging. We characterized the
      Cu(I)-d(A)(5) and Cu(II)-d(A)(7) complexes by (1)H-NMR and (31)P-NMR or frozen
      solution ESR spectroscopy, respectively. Cu(I) is probably coordinated to d(A)(5)
      via N1 and N7 of two adenine residues and possibly also via two
      phosphate/bridging water molecules. The ESR data suggest Cu(II) chelation through
      two nitrogen atoms of the adenine bases and two oxygen atoms (phosphates or water
      molecules). We conclude that oligonucleotides at micromolar concentrations
      prevent Fe(II)/Cu(I/II)-induced oxidative damage, primarily through metal ion
      chelation. Furthermore, we propose the use of a short, metabolically stable
      oligonucleotide, (2'-OMe-A)(5), as a highly potent and relatively long lived
      (t(1/2) approximately 20 h) antioxidant.

PMID- 20155380
TI  - Laparoscopic anterior resection.
AB  - Laparoscopic colectomy for cancer is increasingly practiced worldwide in the last
      2 decades. However, due to procedural complexity, laparoscopic rectal cancer
      excision had not proceeded at a similar pace. This article deals with the
      technique of laparoscopic anterior resection. Resection of rectosigmoid or upper
      rectal tumors is first described, followed by the more difficult sphincter-saving
      total mesorectal excision. We have been using and modifying this technique of
      laparoscopic anterior resection for rectal cancer since 1990 s. In our recent
      review, the local recurrence rate was 7.4%, and the overall 5-year survival was
      70%. Our data suggest laparoscopic resection for rectal cancer is safe and is the
      procedure of choice in selected patients.

PMID- 20155381
TI  - Laparoscopic anterior resection.

PMID- 20155383
TI  - Cell encapsulation using biopolymer gels for regenerative medicine.
AB  - There has been a consistent increase in the mean life expectancy of the
      population of the developed world over the past century. Healthy life expectancy,
      however, has not increased concurrently. As a result we are living a larger
      proportion of our lives in poor health and there is a growing demand for the
      replacement of diseased and damaged tissues. While traditionally tissue grafts
      have functioned well for this purpose, the demand for tissue grafts now exceeds
      the supply. For this reason, research in regenerative medicine is rapidly
      expanding to cope with this new demand. There is now a trend towards supplying
      cells with a material in order to expedite the tissue healing process. Hydrogel
      encapsulation provides cells with a three dimensional environment similar to that
      experienced in vivo and therefore may allow the maintenance of normal cellular
      function in order to produce tissues similar to those found in the body. In this
      review we discuss biopolymeric gels that have been used for the encapsulation of
      mammalian cells for tissue engineering applications as well as a brief overview
      of cell encapsulation for therapeutic protein production. This review focuses on
      agarose, alginate, collagen, fibrin, hyaluronic acid and gelatin since they are
      widely used for cell encapsulation. The literature on the regeneration of
      cartilage, bone, ligament, tendon, skin, blood vessels and neural tissues using
      these materials has been summarised.

PMID- 20155382
TI  - Performing real-time interactive fiber tracking.
AB  - Fiber tracking is a technique that, based on a diffusion tensor magnetic
      resonance imaging dataset, locates the fiber bundles in the human brain. Because
      it is a computationally expensive process, the interactivity of current fiber
      tracking tools is limited. We propose a new approach, which we termed real-time
      interactive fiber tracking, which aims at providing a rich and intuitive
      environment for the neuroradiologist. In this approach, fiber tracking is
      executed automatically every time the user acts upon the application.
      Particularly, when the volume of interest from which fiber trajectories are
      calculated is moved on the screen, fiber tracking is executed, even while it is
      being moved. We present our fiber tracking tool, which implements the real-time
      fiber tracking concept by using the video card's graphics processing units to
      execute the fiber tracking algorithm. Results show that real-time interactive
      fiber tracking is feasible on computers equipped with common, low-cost video
      cards.

PMID- 20155384
TI  - Isolation and characterization of a novel glycogen synthase kinase-3 gene, GmGSK,
      in Glycine max L. that enhances abiotic stress tolerance in Saccharomyces
      cerevisiae.
AB  - A novel glycogen synthase kinase-3 gene, GmGSK, was isolated from Glycine max. It
      is 1,596 bp in length with one ORF of 410 amino acids. Southern blot analysis
      revealed that it has at least two copies in the G. max genome. GmGSK, when
      transiently expressed in Nicotiana tabacum leaves, was localized in both cell
      membrane and cytoplasm. Northern blot analysis indicated that GmGSK is expressed
      in all tissues, with highest expression in the root. GmGSK can be induced by
      various abiotic stresses. When transformed with GmGSK, Saccharomyces cerevisiae
      exhibited enhanced resistance to salt and drought stress.

PMID- 20155385
TI  - Dual bio-responsive gene delivery via reducible poly(amido amine) and survivin
      inducible plasmid DNA.
AB  - A bioreducible poly(amido amine) (SS-PAA) gene carrier, known as poly (amido
      butanol) (pABOL), was used to transfect a variety of cancer and non-cancer cell
      lines. To obtain cancer-specific transgene expression for therapeutic efficiency
      in cancer treatment, we constructed survivin-inducible plasmid DNA expressing the
      soluble VEGF receptor, sFlt-1, downstream of the survivin promoter (pSUR-sFlt-1).
      Cancer-specific expression of sFlt-1 was observed in the mouse renal carcinoma
      (RENCA) cell line. pABOL enhanced the efficiency of gene delivery compared to
      traditional carriers used in the past. Thus, a dual bio-responsive gene delivery
      system was developed by using bioreducible p(ABOL) for enhanced intracellular
      gene delivery and survivin-inducible gene expression system (pSUR-sFlt-1 or pSUR
      Luc reporter gene) that demonstrates increased gene expression in cancer that has
      advantages over current gene delivery systems.

PMID- 20155386
TI  - A potentially immunologically inert derivative of the reverse tetracycline
      controlled transactivator.
AB  - The archetypical system for regulating heterologous gene expression in mammalian
      cells involves tetracycline-activated transactivators (rtTA). Binding of such
      transactivators to tet-operator-controlled promoters induces transcription.
      Immune responses directed against the transactivator proteins may limit the
      applicability of this system in immune-competent hosts. To circumvent such immune
      responses the immune evasion mechanism of the Epstein-Barr virus Nuclear-Antigen
      1 was exploited. Our data show that fusion of the rtTA with the EBNA-1 derived
      Gly-Ala repeat yielded an efficient transactivator with no detectable activity in
      absence of inducer. Antigenic peptides of the fusion protein were not presented
      in MHC class I.

PMID- 20155387
TI  - Surface properties and sub-surface aggregate assimilation of rhamnolipid
      surfactants in different aqueous systems.
AB  - Tensioactive properties of rhamnolipids produced by a Pseudomonas aeruginosa
      strain were investigated in the presence or absence of Sr(2+) or Pb(2+). Surface
      and interfacial properties, and aggregate forming properties and morphologies
      were studied by various techniques including scanning electron microscopy. When
      the pH of a rhamnolipid aqueous solution (40 mg/l) was increased from 5 to 8,
      irregular vesicles gradually took the shape of oligo-vesicles, then regular
      vesicles and finally smaller spherical vesicles. Addition of metal ions
      controlled the aggregates' morphology and stability, and influenced the surface
      and interfacial behavior of rhamnolipid solutions.

PMID- 20155389
TI  - Characteristics of rhVEGF release from topical hydrogel formulations.
AB  - PURPOSE: To study recombinant human vascular endothelial growth factor (rhVEGF),
      the release characteristics from topical gel formulations, and its interaction
      with the gelling agents. METHODS: The release kinetics were followed by
      quantifying rhVEGF that diffused into the receptor chamber of Franz cells.
      Analytical ultracentrifuge (AUC) was used to characterize the sedimentation
      velocity of rhVEGF experienced in the gel. The interactions were characterized by
      isothermal calorimetry (ITC), and rhVEGF conformation was assessed by circular
      dichroism (CD). RESULTS: The fraction of protein released was linear with the
      square root of time. The release rate constants did not show significant change
      within a wide range of bulk viscosities created by different concentrations of
      hydroxypropyl methylcellulose (HPMC) or MC gels. Sedimentation velocity
      determined by AUC generated comparable sedimentation coefficients of protein in
      these gels. AUC and ITC revealed no significant interaction between rhVEGF and
      HPMC and some change on secondary structure of the protein by Far UV CD, which
      was not the case with carboxymethyl cellulose (CMC). CONCLUSIONS: Microviscosity,
      not bulk viscosity, was the key factor for the release of rhVEGF from cellulosic
      gels such as HPMC. Interaction between rhVEGF and CMC resulted in slower, and
      reduced amount of, release from the gel.

PMID- 20155388
TI  - New techniques for drug delivery to the posterior eye segment.
AB  - Ocular drug delivery has become an increasingly important field of research
      especially when treating posterior segment diseases of the eye, such as age
      related macular degeneration, diabetic retinopathy, posterior uveitis and
      retinitis. These diseases are the leading causes of vision loss in developed
      countries which require repeated long-term administration of therapeutic agents.
      New drugs for the medication of the posterior ocular segment have emerged, but
      most drugs are delivered by repeated intravitreal injections associated with
      ocular complications. Advances in ocular drug delivery system research are
      expected to provide new tools for the treatment of the posterior segment
      diseases, providing improved drug penetration, prolonged action, higher efficacy,
      improved safety and less invasive administration, resulting in higher patient
      compliance. This review provides an insight into the recent progress and trends
      in ocular drug delivery systems for treating posterior eye segment diseases, with
      an emphasis on transscleral iontophoresis.

PMID- 20155390
TI  - Mechanism of Trypanosoma cruzi death induced by Cratylia mollis seed lectin.
AB  - Incubation of T. cruzi epimastigotes with the lectin Cramoll 1,4 in Ca(2+)
      containing medium led to agglutination and inhibition of cell proliferation. The
      lectin (50 microg/ml) induced plasma membrane permeabilization followed by Ca(2+)
      influx and mitochondrial Ca(2+) accumulation, a result that resembles the
      classical effect of digitonin. Cramoll 1,4 stimulated (five-fold) mitochondrial
      reactive oxygen species (ROS) production, significantly decreased the electrical
      mitochondrial membrane potential (Delta Psi(m)) and impaired ADP phosphorylation.
      The rate of uncoupled respiration in epimastigotes was not affected by Cramoll
      1,4 plus Ca(2+) treatment, but oligomycin-induced resting respiration was 65%
      higher in treated cells than in controls. Experiments using T. cruzi
      mitochondrial fractions showed that, in contrast to digitonin, the lectin
      significantly decreased Delta Psi(m) by a mechanism sensitive to EGTA. In
      agreement with the results showing plasma membrane permeabilization and
      impairment of oxidative phosphorylation by the lectin, fluorescence microscopy
      experiments using propidium iodide revealed that Cramoll 1,4 induced
      epimastigotes death by necrosis.

PMID- 20155391
TI  - Testing the equal environments assumption in the Children of Twins design.
AB  - In a Children of Twins (COT) design, the environmental and genetic risk of a
      child is, in part, dependent upon the status of the father and the father's
      cotwin. The logic of the COT method breaks down if the zygosity of the twin pair
      is confounded with the environment provided to the child (a version of the Equal
      Environment Assumption, EEA). If MZ twin fathers see each other more often than
      DZ twin fathers, and a child's uncle is the affected twin in discordant pairs,
      this could increase the environmental risk of children of MZ over that of DZ
      discordant twins. The current study was designed to test the EEA in the COT
      design, specifically in children of alcohol and drug dependent fathers. Results
      indicated that MZ twins did have more contact than DZ twins. Regression analyses
      were conducted to predict child externalizing symptom counts from father's
      zygosity group status, level of contact with father's cotwin, and their
      interaction. Results found no significant interaction between father's zygosity
      and the higher level of cotwin contact (seen in MZ twins) in predicting several
      measures of offspring externalizing risk. The results of this study suggested
      that the COT design does not confound zygosity with differences in environmental
      risk exposure, findings that support the validity of the EEA within this research
      context.

PMID- 20155393
TI  - Introduction to the special issue, pathways between genes, brain, and behavior.
AB  - In the past 10 years or so, with the sequencing of the human genome and rapid
      advances in the development of high throughput techniques, the field of behavior
      genetics has increasingly moved toward the detection of actual genes and
      environmental factors. However, the field is still in the relatively early stages
      of understanding some of the basic facts about the complex genetic underpinnings
      of brain structure and function and their relationship to behavior. The 15
      articles in this special issue were selected to represent the diversity of
      methodologies applied to the complexity of pathways linking genes, brain, and
      behavior. While providing strong evidence for the role of genes in individual
      differences in brain structure and function, these papers also demonstrate that
      environmental experiences alter neurobiological pathways, and that genetic
      factors may further moderate the impact of environmental experience. Most
      importantly, the breadth of studies proves that in order to be able to trace the
      pathways between genes, brain, and behavior, we need experts in genetics,
      neuroscience, psychology, and psychiatry.

PMID- 20155394
TI  - Brain pathways mediating the pro-aggressive effect of the steroid sulfatase (Sts)
      gene.
AB  - STS is the single enzyme that converts all steroid sulfates into their free
      steroid forms. Initiation of attack behavior against conspecific male mice
      appeared to be linked to Sts. Here we have confirmed the role of Sts through an
      association study with attack behavior. Previous studies indicated a positive
      correlation between the initiation of attack behavior and liver STS concentration
      levels in male mice, but this finding was not compatible with established
      knowledge of STS mechanisms. High STS concentrations induce low concentrations of
      sulfated steroids. Sulfated and un-sulfated steroids are GABA(A) receptor
      agonists and NMDA receptor positive allosteric modulators. This synaptic pattern
      of functioning can generate attack behavior and we have confirmed here that an
      injection of the sulfated steroid dehydroepiandrosterone sulfate (DHEA-S)
      increases attack behavior. To solve the paradox, we measured the transcription
      activity of the genes underlying the pathways involved in the hydrolysis of
      sulfated steroids and leading to the formation of un-conjugated steroids in the
      mouse brain. We observed that the genes monitoring the steroid biosynthesis
      pathways exhibited a transcription pattern resulting in an increased
      sulfotransferase activity in the attacking males that could counterbalance the de
      sulfating activity of Sts in the attacking mice.

PMID- 20155392
TI  - Brain electrophysiological endophenotypes for externalizing psychopathology: a
      multivariate approach.
AB  - Abnormalities in electrophysiological measures of stimulus-evoked brain activity
      (including the P3 event-related potential (ERP) and its associated delta and
      theta time-frequency (TF) components), and intrinsic, resting state brain
      activity (including EEG in the beta frequency band) have each been associated
      with biological vulnerability to a variety of externalizing (EXT) spectrum
      disorders, such as substance use disorders, conduct disorder, and antisocial
      behavior. While each of these individual measures has shown promise as an
      endophenotype for one or more aspects of EXT, we proposed that the power to
      identify EXT-related genes may be enhanced by using these measures collectively.
      Thus, we sought to explore a multivariate approach to identifying
      electrophysiological endophenotypes related to EXT, using measures identified in
      the literature as promising individual endophenotypes for EXT. Using data from
      our large twin sample (634 MZ and 335 DZ, male and female same-sex pairs), and
      fitting multivariate biometric Cholesky models, we found that these measures (1)
      were heritable, (2) showed significant phenotypic and genetic correlation with a
      general vulnerability to EXT (which is itself highly heritable), (3) showed
      modest phenotypic and genetic correlation with each other, and (4) were sensitive
      to genetic effects that differed as a function of gender. These relationships
      suggest that these endophenotypes are likely tapping into neurophysiological
      processes and genes that are both common across them and unique to each-all of
      which are relevant to a biological vulnerability to EXT psychopathology.

PMID- 20155396
TI  - Characterization of monocarboxylate transporter 1 (MCT1) binding affinity for
      Basigin gene products and L1cam.
AB  - The purpose of this study was to determine the binding affinities of Basigin gene
      products and neural cell adhesion molecule L1cam for monocarboxylate transporter
      1 (MCT1). ELISA binding assays were performed in which recombinant proteins of
      the transmembrane domains of Basigin gene products and L1cam were incubated with
      MCT1 captured from mouse brain. It was determined that Basigin gene products bind
      MCT1 with moderate affinity, but L1cam does not bind MCT1. Despite a high degree
      of sequence conservation between Basigin gene products and L1cam, the sequences
      are different enough to prevent L1cam from interacting with MCT1.

PMID- 20155395
TI  - Maintenance of critical properties of brain tumor stem-like cells after
      cryopreservation.
AB  - It would be very useful to be able to classify brain tumor stem cells (BTSCs) by
      certain criteria to afford the design of specific or individualized treatment.
      Here, we studied two BTSC lines with differing biological and molecular features
      and whose respective features were well preserved after cryopreservation as
      single cells in SFM or 90% serum with 10% DMSO, a method not previously reported.
      The resuscitated BTSCs shared properties indistinguishable from their respective
      parental cells, including tumor sphere forming potentials, growth and
      differentiation properties, and tumorigenesis in vivo. The two cell lines also
      had differing molecule profiles, which can be well preserved after
      cryopreservation, similar to that of their respective primary tumors. Therefore,
      BTSCs from different patients, that have their own properties, were well retained
      by the present cryopreservation method, which might be a useful and reliable
      method for preserving BTSCs for long-term studies, such as classification and
      specific therapy design.

PMID- 20155397
TI  - Fitness aspects of transgenic Aedes fluviatilis mosquitoes expressing a
      Plasmodium-blocking molecule.
AB  - Vector-born diseases cause millions of deaths every year globally. Alternatives
      for the control of diseases such as malaria and dengue fever are urgently needed
      and the use of transgenic mosquitoes that block parasite/virus is a sound
      strategy to be used within control programs. However, prior to use transgenic
      mosquitoes as control tools, it is important to study their fitness since
      different biological aspects might influence their ability to disseminate and
      compete with wild populations. We previously reported the construction of four
      transgenic Aedes fluviatilis mosquito lines expressing a Plasmodium- blocking
      molecule (mutated bee venom phospholipase A(2)-mPLA(2)). Presently we studied two
      aspects of their fitness: body size, that has been used as a fitness-related
      status, and the expression of major enzymes classes involved in the metabolism of
      xenobiotics, including insecticides. Body size analysis (recorded by geometric
      wing morphometrics) indicated that both male and female mosquitoes were larger
      than the non-transgenic counterparts, suggesting that this characteristic might
      have an impact on their overall fitness. By contrast, no significant difference
      in the activity of enzymes related to metabolic insecticide resistance was
      detected in transgenic mosquitoes. The implication on fitness advantage of these
      features, towards the implementation of this strategy, is further discussed.

PMID- 20155398
TI  - Choosing for the child with cochlear implants: a note of precaution.
AB  - Recent contributions to discussions on paediatric cochlear implantation in Norway
      indicate two mutually exclusive doctrines prescribing the best course of post
      operative support for a child with cochlear implants; bilingually with sign
      language and spoken language simultaneously or primarily monolingually with
      speech only. This conflict constitutes an ethical problem for parents responsible
      for choosing between one of the two alternatives. This article puts forth the
      precautionary principle as a possible solution to this problem. Although
      scientific uncertainty exists in the case of both doctrines, there exists a
      scenario of possible irreversible harm to some of the children habilitated
      monolingually. An application of the precautionary principle may hence suggest
      that it is rational to agree on the bilingual approach, at least for the time
      being.

PMID- 20155399
TI  - Epigenetic inactivation of the thyroid hormone receptor beta1 gene at 3p24.2 in
      lung cancer.
AB  - BACKGROUND: Frequent allelic loss on chromosome 3p in various human cancers
      suggests the presence of tumor suppressor genes in this region. The thyroid
      hormone receptor beta1 (TRbeta1) gene is located at 3p24.2, where allelic loss
      frequently occurs in lung cancer, and aberrant TRbeta1 methylation was observed
      in several human cancers. METHODS: We examined the expression, mutation, and
      promoter methylation of TRbeta1 in 18 small cell lung cancer (SCLC) and 29 non
      small cell lung cancer (NSCLC) cell lines by reverse-transcription polymerase
      chain reaction (RT-PCR), direct sequencing, or methylation-specific PCR. Four
      lung cancer cell lines lacking TRbeta1 expression were treated with 5-aza-2-deoxy
      cytidine and/or trichostatin-A, and the TRbeta1 expression was determined by RT
      PCR. We also examined the TRbeta1 methylation in 116 NSCLC surgical specimens and
      analyzed the correlation between methylation status and clinicopathological
      parameters or mutations of KRAS and EGFR. RESULTS: TRbeta1 expression was absent
      in 61% of SCLCs and 48% of NSCLCs, and 67% of SCLCs and 45% of NSCLCs carried
      TRbeta1 promoter methylation, while no somatic mutation was found in all cell
      lines. TRbeta1 methylation status was significantly associated with loss of
      TRbeta1 expression. TRbeta1 expression was restored by treatment with 5-aza-2
      deoxy-cytidine and/or trichostatin-A in four cell lines. TRbeta1 methylation was
      found in 47% of NSCLC surgical specimens; however, the methylation was not
      significantly associated with any clinicopathological parameters or mutations of
      KRAS and EGFR. CONCLUSIONS: This is the first study to demonstrate epigenetic
      inactivation of TRbeta1 through aberrant methylation in lung cancer, while
      TRbeta1 mutations are not common in lung cancer.

PMID- 20155400
TI  - Intraoperative imprint cytology examination of sentinel lymph nodes after
      neoadjuvant chemotherapy in breast cancer patients.
AB  - BACKGROUND: Intraoperative imprint cytology (IC) is one of several accurate,
      proven methods to detect tumor cells in sentinel lymph nodes (SLN) from patients
      with operable breast cancer. In patients treated with neoadjuvant chemotherapy
      (NAC), studies have demonstrated the feasibility and accuracy of SLN biopsy
      procedure. We evaluated the validity of IC for SLN testing in patients after NAC.
      MATERIAL AND METHODS: Patients with infiltrating breast carcinoma receiving NAC
      (n = 132) were studied prospectively. At surgery, SLN biopsy followed by axillary
      lymph node dissection was performed. SLN were evaluated using IC in 80 of 132
      patients (60%). The results of IC in the adjuvant setting (100 patients) were
      used for comparison. RESULTS: SLN metastases were correctly identified using IC
      in 58 of 80 (72%) patients. False negative results were observed in 21 patients.
      The sensitivity of IC testing was 38.2% and specificity 97.8%. The positive and
      negative predictive values (PPV and NPV) were 92.9% and 68.2%, respectively. In
      univariate analysis and multivariate logistic regression analysis, patients with
      micrometastases or isolated tumor cells in SLN have 2.3 times higher risk of a
      false negative IC result than patients with macrometastases in SLN (P = .00021;
      relative risk [RR] = 2.3; 95% confidence interval, 1.37-3.85). The non-NAC group,
      which contained fewer micrometastatic cases, showed better sensitivity (47.4%)
      and NPV (88.9%). CONCLUSION: NAC does not seem to influence the accuracy and
      sensitivity of IC. Variations in sensitivity are related to the proportion of
      cases with micrometastases and ITC, as it was also shown in chemonaive patients.

PMID- 20155401
TI  - A simple risk score to predict in-hospital mortality after pancreatic resection
      for cancer.
AB  - BACKGROUND: Pancreatectomy for cancer continues to have substantial perioperative
      risk, and the factors affecting mortality are ill defined. An integer-based risk
      score based on national data might help clarify the risk of in-hospital mortality
      in patients undergoing pancreatic resection. METHODS: Records with the diagnosis
      of pancreatic cancer were queried from the Nationwide Inpatient Sample for 1998
      2006. Procedures were categorized as proximal, distal, or nonspecified
      pancreatectomies on the basis of ICD-9 codes. Logistic regression and bootstrap
      methods were used to create an integer risk score for estimating the risk of in
      hospital mortality using patient demographics, comorbidities (Charlson
      comorbidity score), procedure, and hospital type. A random sample of 80% of the
      cohort was used to create the risk score with a 20% internal validation set.
      RESULTS: A total of 5715 patient discharges were identified. Composite in
      hospital mortality was 5.8%. Predictors used for the final model were age group,
      Charlson score, sex, type of pancreatectomy, and hospital volume status (low-,
      medium-, or high-volume center). Integer values were assigned to these
      characteristics and then used for calculating an additive score. Three clinically
      useful score groups were defined to stratify the risk of in-hospital mortality
      (mortality was 2.0, 6.2, and 13.9%, respectively; P < 0.0001), with a 6.95-fold
      difference between the low- and high-risk groups. There was sufficient
      discrimination of both the derivation set and the validation set, with c
      statistics of 0.71 and 0.72, respectively. CONCLUSIONS: An integer-based risk
      score can be used to accurately predict in-hospital mortality after
      pancreatectomy and may be useful for preoperative risk stratification and patient
      counseling.

PMID- 20155402
TI  - Antidermatophyte and antimelanogenesis compound from Eleutherine americana grown
      in Indonesia.
AB  - An active compound from the bulb of Eleutherine americana L. Merr. (Iridaceae)
      collected from East Kalimantan, Indonesia, was tested for its antidermatophyte
      and antimelanogenesis activity. Antifungal assay-directed fractionation of the n
      hexane-soluble fraction of the methanolic extract of the bulb of E. americana led
      to the isolation of 1 as an active compound. The compound was identified as the
      naphthoquinone eleutherin by EI-MS and (1)H-, (13)C-, and two-dimensional NMR
      analyses. Antidermatophyte assay of 1 at concentrations of 10, 20, 40, 60, and 80
      microg/disk and myconazole, a commercial antidermatophyte, at 10 microg/disk
      displayed 7, 8, 13, 16, 17, and 14 mm of inhibition zone against Trichophyton
      mentagrophytes, respectively. In a melanin formation inhibition assay, compound 1
      displayed potent antimelanogenesis activity at 5 ppm with low toxicity compared
      with arbutin, a commercial skin-whitening agent. The results showed the high
      potential of 1, an active compound from E. americana, to be applied as an
      antidermatophyte and antimelanogenesis agent.

PMID- 20155403
TI  - Ameliorating effects of Kangen-karyu on neuronal damage in rats subjected to
      repeated cerebral ischemia.
AB  - We previously reported that 21-day (14-day pre-ischemic and 7-day post-ischemic)
      treatment with Kangen-karyu (KGKR) improved spatial memory impairment and
      hippocampal neuronal death induced by repeated cerebral ischemia (2 x 10-min, 1-h
      interval) in rats. In the present study, we examined the effect of single and 14
      day pre-ischemic KGKR treatment on neuronal damage in the same repeated cerebral
      ischemia model. Additionally, to determine the mechanisms of neuroprotection by
      KGKR at glutamatergic neurons, we examined the effects of KGKR on glutamate
      release induced by repeated cerebral ischemia in vivo, and on cell damage induced
      by both glutamate and kainate in primary cultured hippocampal neurons in vitro.
      The 14-day pre-ischemic KGKR (300 mg/kg, oral administration (p.o.)) treatment
      reduced neuronal damage and astrocyte expression induced by repeated cerebral
      ischemia. No effect was observed after single pre-ischemic KGKR treatment. Both
      single and 14-day KGKR treatment decreased glutamate release in the hippocampal
      CA1 region in intact rats; however, neither pre-ischemic KGKR treatment altered
      glutamate release during cerebral ischemia. In vitro, KGKR (100-1000 microg/mL)
      dose-dependently suppressed hippocampal neuronal damage induced by both glutamate
      (100 microM) and kainate (1 mM). These data suggest neuroprotection with KGKR
      requires continuous pre-ischemic treatment, and that the mechanisms of protection
      may be involved in inhibiting the glutamatergic receptors of the post-synaptic
      neurons.

PMID- 20155404
TI  - Developing a framework for assessing responsible conduct of research education
      programs.
AB  - Education in the responsible conduct of research (RCR) in the United States has
      evolved over the past decade from targeting trainees to including educational
      efforts aimed at faculty and staff. In addition RCR education has become more
      focused as federal agencies have moved to recommend specific content and to
      mandate education in certain areas. RCR education has therefore become a research
      compliance issue necessitating the development of policies and the commitment of
      resources to develop or expand systems for educating faculty and staff and for
      assuring compliance. These changes implied the need to develop a program
      evaluation model that could be applied to institutional RCR education programs,
      which were expected to differ from traditional academic credit-bearing courses
      targeting trainees. Information gleaned from the examination of corporate
      compliance models was analyzed in order to create a program evaluation module
      that could be used to document and assess educational programs focused on
      teaching RCR. A programmed series of questions for each of the nine RCR content
      areas identified by the United States Office of Research Integrity was created
      based on a performance-monitoring evaluation model. The questions focus on
      educational goals, resources provided to support the educational efforts,
      educational content, content delivery, educational outcomes, compliance
      requirements and feedback. Answers collected in response to the questions could
      be used to both document and continually improve the quality of RCR educational
      programs through on-going formative assessment and feedback.

PMID- 20155405
TI  - The role of PET-CT in the differential diagnosis of thymic mass after treatment
      of patients with lymphoma.
AB  - Thymic hyperplasia is a common phenomenon in both children and young adults after
      chemotherapy and may explain the finding of a mediastinal mass in patients with
      malignant lymphoma after complete remission. In the present study, we report 5
      cases with malignant lymphoma presenting with a mediastinal mass on CT scan after
      completion of chemotherapy diagnosed as thymic hyperplasia by PET-CT imaging. We
      retrospectively analyzed 5 patients who presented with anterior mediastinal
      masses a median of 4 months (range 3-6) after achieving complete remission
      following successful treatment for malignant lymphoma. Three patients were
      diagnosed with Hodgkin's lymphoma (HL) and the others with non-Hodgkin's lymphoma
      (NHL). The median age of the patients was 23 (range of 18-47). PET-CT was
      performed on these patients to determine the characteristics of a mass which had
      been detected on CT. PET-CT was performed for all patients, and the thymic masses
      demonstrated only mild FDG uptake considered to be consistent with thymic
      hyperplasia. During a median of 24 months of follow-up, all patients were
      recurrence-free with a median survival of 15 months (range 10-26 months). It is
      important to be aware of the possibility of thymic hyperplasia after chemotherapy
      to avoid misdiagnosis or over-staging of disease, as well as unnecessary
      biopsies, especially when the presenting anterior mediastinal mass was originally
      located near the thymus on CT scan. Mild FDG PET uptake was sufficient for the
      diagnosis of benign disease in the cases in this study.

PMID- 20155407
TI  - Changes in the number of resident publications after inception of the 80-hour
      work week.
AB  - BACKGROUND: Since the inception of resident work-hour regulations, there has been
      considerable concern regarding the influence of decreased work hours on graduate
      medical education. In particular, it is unclear whether implementation of work
      hour restrictions has influenced resident academic performance as defined by
      quantity of peer-reviewed publications while participating in graduate medical
      education. QUESTIONS/PURPOSES: We determined the impact of work-hour changes on
      resident involvement in the number of published clinical studies, laboratory
      research, case reports, and review articles. METHODS: We conducted a PubMed
      literature search of 139 consecutive orthopaedic surgery residents (789 total
      resident-years) at one institution from academic years 1995-1996 to 2008-2009.
      This represented a continuous timeline before and after implementation of work
      hour restrictions. The number of resident publications before and after
      implementation of work-hour changes was compared. RESULTS: There was a greater
      probability of peer review authorship in any given resident-year after work-hour
      changes than before. Average publications per resident-year increased for total
      articles, clinical articles, case reports, and reviews. There was an increased
      rate of publications in which the resident was the first author. CONCLUSIONS:
      Since implementation of work-hour changes, total resident publications and
      publications per resident-year have increased.

PMID- 20155408
TI  - 14-3-3 proteins and spinocerebellar ataxia type 1: from molecular interaction to
      human neuropathology.
AB  - This mini-review focuses on the possible relevance of 14-3-3 proteins in
      spinocerebellar ataxia type 1 (SCA1). 14-3-3 proteins are mainly localized in the
      synapses and neuronal cytoplasm, and seven isoforms have been identified in
      mammals. This family of proteins was initially identified as adaptor proteins
      which bind to phosphoserine-containing motifs. Binding motifs and potential
      functions of 14-3-3 proteins are now recognized to have a wide range of
      functional relevance. SCA1 is an autosomal-dominant neurodegenerative disorder
      and is linked to polyglutamine expansion (ataxin-1 protein). The Zoghbi and Orr
      group showed direct interaction of 14-3-3 proteins with ataxin-1 where nuclear
      recruitment of the ataxin-1 protein is dependent on its phosphorylation. This
      targeted binding of 14-3-3 protein to phosphorylated ataxin-1 to stabilize ataxin
      1 in cellular models was corroborated by our double-labeling study for expanded
      polyglutamine and 14-3-3 proteins which demonstrated colocalization of these two
      epitopes in the neuronal nuclei in human autopsied brains with SCA1. Ataxin-1/14
      3-3 protein interaction is a new potential target for therapeutic intervention in
      the treatment of SCA1.

PMID- 20155409
TI  - Leukemia-associated genetic aberrations in mesenchymal stem cells of children
      with acute lymphoblastic leukemia.
AB  - Childhood acute lymphoblastic leukemia (ALL) is caused by malignant immature
      lymphocytes. Even though childhood ALL can be cured in a large number of
      patients, around 20% of the patients suffer a relapse after chemotherapy. The
      origin of the relapse is unclear at the present time. Given the high plasticity
      of cells, we searched for leukemia-associated genetic aberrations and
      immunoglobulin (IG) gene rearrangements in mesenchymal stem cells (MSC) from
      childhood B-cell precursor ALL patients. MSC from all ten ALL patients analyzed
      presented the chromosomal translocations that had been detected in leukemia cells
      (TEL-AML1, E2A-PBX1, or MLL rearrangement). The proportions of translocation
      positive MSC varied between 10% and 54% depending on the patients and the time
      point of analysis. Leukemia-specific IG gene rearrangements were detected in the
      MSC from three ALL patients. The detection of leukemia-associated genetic
      aberrations in MSC indicates a clonal relationship between MSC and leukemia cells
      and suggests their involvement in the pathogenesis and/or pathophysiology of
      childhood ALL.

PMID- 20155410
TI  - Genetic and physical fine mapping of Scmv2, a potyvirus resistance gene in maize.
AB  - Sugarcane mosaic virus (SCMV) is an important virus pathogen both in European and
      Chinese maize production, causing serious losses in grain and forage yield in
      susceptible cultivars. Two major resistance loci confer resistance to SCMV, one
      located on chromosome 3 (Scmv2) and one on chromosome 6 (Scmv1). We developed a
      large isogenic mapping population segregating in the Scmv2, but not the Scmv1
      region, to minimize genetic variation potentially affecting expression of SCMV
      resistance. We fine mapped Scmv2 to a region of 0.28 cM, covering a physical
      distance of 1.3426 Mb, and developed six new polymorphic SSR markers based on
      publicly available BAC sequences within this region. At present, we still have
      three recombinants left between Scmv2 and the nearest polymorphic marker on
      either side of the Scmv2 locus. The region showed synteny to a 1.6 Mb long
      sequence on chromosome 12 in rice. Analysis of the public B73 BAC library as well
      as the syntenic rice region did not reveal any similarity to known resistance
      genes. However, four new candidate genes with a possible involvement in movement
      of virus were detected.

PMID- 20155411
TI  - Creation and evaluation of a two-dimensional contour plot of fatty acid methyl
      esters after off-line coupling of reversed-phase HPLC and GC/EI-MS.
AB  - Fatty acid methyl esters obtained from a fish oil sample were fractionated by non
      aqueous reversed-phase high-performance liquid chromatography (RP-HPLC) using
      three serially connected C(18)-columns and pure methanol as the eluent. The HPLC
      fractions were analyzed by gas chromatography-electron ionization mass
      spectrometry in the selected ion monitoring mode. Data analysis and visualization
      was performed by the creation of a two-dimensional (2D) contour plot, in which GC
      retention times were plotted against the HPLC fractions. The 2D contour plot
      resulted in a full resolution of more than 120 fatty acids. The fatty acids were
      arranged on predictable lines and curves in dependence of the number of carbons
      and double bonds. The 2D contour plot enabled both the recognition of unknown
      fatty acids (which were found off the lines and curves) and the prediction of the
      coordinates of known fatty acids. Finally, selected HPLC fractions were subjected
      to further experiments (hydrogenation, silver ion fractionation, specific GC/MS
      measurements) in order to verify the structural assignments predicted from the 2D
      contour plot. All in all, the structures of over 100 FAs could be assigned to the
      peaks detected in the 2D contour plots.

PMID- 20155412
TI  - Geostatistical and multivariate statistical analysis of heavily and manifoldly
      contaminated soil samples.
AB  - The surroundings of the former Kremikovtzi steel mill near Sofia (Bulgaria) are
      influenced by various emissions from the factory. In addition to steel and
      alloys, they produce different products based on inorganic compounds in different
      smelters. Soil in this region is multiply contaminated. We collected 65 soil
      samples and analyzed 15 elements by different methods of atomic spectroscopy for
      a survey of this field site. Here we present a novel hybrid approach for
      environmental risk assessment of polluted soil combining geostatistical methods
      and source apportionment modeling. We could distinguish areas with heavily and
      slightly polluted soils in the vicinity of the iron smelter by applying
      unsupervised pattern recognition methods. This result was supported by
      geostatistical methods such as semivariogram analysis and kriging. The modes of
      action of the metals examined differ significantly in such a way that iron and
      lead account for the main pollutants of the iron smelter, whereas, e.g., arsenic
      shows a haphazard distribution. The application of factor analysis and source
      apportionment modeling on absolute principal component scores revealed novel
      information about the composition of the emissions from the different stacks. It
      is possible to estimate the impact of every element examined on the pollution due
      to their emission source. This investigation allows an objective assessment of
      the different spatial distributions of the elements examined in the soil of the
      Kremikovtzi region. The geostatistical analysis illustrates this distribution and
      is supported by multivariate statistical analysis revealing relations between the
      elements.

PMID- 20155413
TI  - Cystic fibrosis: a label-free detection approach based on thermally modulated
      electrochemical impedance spectroscopy.
AB  - Cystic fibrosis is one of the most common genetically inherited diseases in
      northern Europe, with the DF508 mutation being the most common, and among the
      Caucasian population being responsible for almost 70% of cases. In this work, we
      report on the use of thermally modulated electrochemical impedance spectroscopy
      for the discrimination of the DF508 mutation from the wild-type sequence. DNA
      probes (15 and 21 bases long) were immobilised on the surface of gold electrodes
      and the variation of the charge-transfer resistance was monitored as a function
      of hybridisation. Two sets of targets were used in this work: synthetic 15-mer
      sequences and two single-stranded synthetic analogues of PCR products 82 (mutant)
      and 85 (wild type) bases long. Hybridisation with short targets resulted in very
      sequence specific charge-transfer-resistance variation with a discrimination
      factor at room temperature between fully complementary and mismatched sequences
      of approximately fivefold. However, in the case of the single-stranded synthetic
      PCR product analogues, a lower discrimination factor was recorded (1.5-fold). The
      effect of temperature was investigated to improve discrimination and the use of a
      posthybridisation wash at elevated temperature resulted in a fivefold improvement
      in the discrimination factor. Using an electrode array with probes immobilised
      against each of the mutant and wild-type sequences, we achieved an unequivocal
      detection of the DF508 mutation.

PMID- 20155414
TI  - Simultaneous quantitative determination of alpha-ketoglutaric acid and 5
      hydroxymethylfurfural in human plasma by gas chromatography-mass spectrometry.
AB  - Alpha-ketoglutaric acid (alpha-KG) and 5-hydroxymethylfurfural (5-HMF) are
      currently under investigation as promising cancer cell damaging agents. A method
      for the simultaneous quantitative determination of alpha-KG and 5-HMF in human
      plasma was established for screening these compounds in human plasma. Plasma
      samples were directly treated with O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine
      hydrochloride to form the corresponding oximes, thus facilitating subsequent
      liquid-liquid extraction. After formation of the trimethylsilyl ethers, samples
      were analyzed by gas chromatography with electron ionization mass spectrometry.
      Stable isotope labeled standards were used, the preparation of (13)C(6)-5-HMF is
      described. Limits of quantitation were set to 0.938 microg/mL for alpha-KG and
      0.156 microg/mL for 5-HMF. Inter-day accuracy was < or = 93.7% (alpha-KG) and <
      or = 92.8% (5-HMF). Inter-day precision was < or = 6.0% (alpha-KG) and < or =
      4.6% (5-HMF). The method has been successfully applied to pharmacokinetic
      profiling of the compounds after intravenous application.

PMID- 20155415
TI  - Coronary artery spasm during radiofrequency ablation of a left lateral accessory
      pathway.
AB  - A 16-year-old female patient with Wolff-Parkinson-White syndrome and
      supraventricular tachycardia underwent radiofrequency (RF) catheter ablation of
      an accessory pathway in the left lateral area. During RF ablation she developed
      reversible ST segment elevation secondary to coronary artery spasm. Coronary
      angiography demonstrated the ablation catheter in close proximity to the
      circumflex coronary artery, with no evidence of coronary artery injury.
      Subsequently, conduction by way of the accessory pathway was successfully
      eliminated with cryoablation with no further coronary spasm or injury.

PMID- 20155416
TI  - Gene replacement strategies to test the functional redundancy of basic helix-loop
      helix transcription factor.
AB  - Basic helix-loop-helix (bHLH) transcription factors control developmental
      decisions for a wide range of embryonic cell types. Hand1 and Hand2 are closely
      related bHLH proteins that control cardiac, craniofacial, and limb development.
      Within the developing heart, Hand1 expression becomes restricted predominantly to
      the left ventricle, whereas Hand2 becomes restricted predominantly to the left
      ventricle, for which findings have shown each Hand factor to be necessary for
      normal chamber formation. Forced overexpression of Hand1 throughout the early
      developing heart induces abnormal interventricular septal development, with
      resulting pathogenesis of congenital heart defects. To investigate the potential
      transcriptional mechanisms involved in heart morphogenesis by Hand2, this study
      used a replacement targeting approach to knock Hand2 into the Hand1 locus and
      ectopically express one copy of Hand2 within the endogenous Hand1 expression
      domain in the developing hearts of transgenic mice. The findings show that high
      percentage Hand1 ( Hand2 ) chimeras die at birth and exhibit a range of
      congenital heart defects. These findings suggest that Hand factors may act via
      unique transcriptional mechanisms mediated by bHLH factor partner choice,
      supporting the notion that alterations of Hand factor stoichiometry may be as
      deleterious to normal heart morphogenesis as Hand factor loss of function.

PMID- 20155417
TI  - Feasibility study of simultaneous physical examination and dynamic MR imaging of
      medial collateral ligament knee injuries in a 1.5-T large-bore magnet.
AB  - OBJECTIVE: To determine the feasibility of evaluating medial knee joint laxity
      with dynamic magnetic resonance (MR) imaging and simultaneous physical joint
      examination in a large-bore 1.5-T system. MATERIALS AND METHODS: The study
      included 10 patients (5 women, 5 men; mean age 35 years) with clinically
      diagnosed and categorized acute injuries of the medial collateral ligament (MCL).
      Intermittent valgus stress was applied separately to both the affected and the
      contralateral knee joint during dynamic MR imaging with a two-dimensional fast
      low-angle shot sequence. The width of the medial joint space and the opening
      angle between the femoral condyles and the tibial plateau were measured. Results
      obtained from dynamic MR imaging of the affected knee were compared with
      morphological MCL changes on static MRI, to kinematics of the contralateral side
      and to the clinical grading of MCL injuries. RESULTS: On clinical examination,
      all patients had grade 2 MCL injuries except one, who had a grade 1 lesion. Using
      morphological MRI criteria, 9 grade II and 1 grade III injuries were seen. Mean
      medial joint space width and opening angles of all affected knees were 2.8 mm and
      2.7 degrees  respectively, compared with 1.7 mm and 2.1 degrees  on the
      contralateral side. The Wilcoxon signed rank test indicated that the differences
      in width (P = 0.005) and opening angle (P = 0.037) between the affected and
      contralateral knees were significant. CONCLUSION: Dynamic MR imaging and
      simultaneous physical joint examination is feasible. Our results suggest that
      this technique might enable the imaging documentation of medial ligamentous knee
      instability.

PMID- 20155418
TI  - Magnetic resonance imaging of anatomical variations in the knee. Part 1:
      ligamentous and musculotendinous.
AB  - Magnetic resonance imaging (MRI) is now the modality of choice for the
      investigation of internal derangement of the knee. Technological advances,
      including the wider availability of stronger magnets and new sequences, allows
      improved visualisation of smaller structures. Normal variants must be recognised
      as such, so that both over-investigation and mis-diagnosis are avoided. This
      article reviews both the well-recognised and the less common ligamentous and
      musculotendinous anatomical variants within the knee and illustrates their
      imaging characteristics on MRI.

PMID- 20155419
TI  - Reconstruction of distal radius by fibula following excision of grade III giant
      cell tumour: follow-up of 18 cases.
AB  - The purpose of this study was to evaluate the long-term results of vascularised
      fibular graft for reconstruction of the wrist after excision of grade III giant
      cell tumour in the distal radius. From January 1998 to September 2003, 18
      patients with wrist defects due to distal radius grade III giant cell tumour
      resection were treated with vascularised fibular graft and were followed-up. The
      limb function was restored to an average 80% of normal function and bone union
      was achieved within six months in 18 patients with vascularised fibular graft.
      MSTS score averaged 25.6 and ranged between 21 and 29; Mayo wrist score averaged
      56 with a range from 40 to 65. It is appropriate to use the head of the fibula as
      a substitute for the distal radius. The healing of vascularised fibular graft is
      very quick and without bone resorption. Thus, in the procedure for reconstruction
      and limb salvage after bone tumour resection of distal radius, the free
      vascularised fibular graft with fibular head is an ideal substitute.

PMID- 20155420
TI  - Viability of loose body fragments in osteochondritis dissecans of the knee. A
      series of cases.
AB  - The purpose of this study was to determine if the cartilage from loose
      osteochondral fragments remains viable. Five patients with OCD of the knee who
      had undergone surgical treatment (arthroscopic reduction and internal fixation of
      the loose body) were included. The average age of patients was 13 years (range 10
      14 years). Cartilage samples were obtained from the loose body fragments before
      reattachment was performed (study group) and from the healthy native cartilage
      (intercondyle area, control group) from each of the five patients. Tissue
      viability was assessed using live-dead assay in both groups. All five loose
      osteochondral fragments showed similar viability to the healthy native cartilage
      group, with 88% cell viability (95% CI 50-100) in loose body fragments versus 92%
      viability (95% CI 50-100) from healthy cartilage. This study showed that
      cartilage from detached OCD fragments remains viable before reattachment is
      performed.

PMID- 20155421
TI  - Association of serum uric acid with lupus nephritis in systemic lupus
      erythematosus.
AB  - The aim of the present study is to assess the association of elevated serum uric
      acid (UA) with lupus nephritis (LN) in systemic lupus erythematosus (SLE)
      patients. A total of 130 SLE patients were recruited, of whom 73 patients
      developed LN. Blood samples were obtained for determination of uric acid,
      complement 3 (C3), C-reactive protein (CRP) and some autoantibodies including
      anti-double-stranded DNA, -Smith, -SSA, -SSB, -U1RNP, SCL-70, and -Jo-1
      antibodies. Correlations of UA with LN were assessed. UA was an independent risk
      factor for LN [odds ratio (95% CI): 1.01 (1.005-1.014); P=0.0000]. The best cut
      off value for UA using the ROC curve was 330 MUmol/L (sensitivity 78.1% and
      specificity 75.4%) and the area under the ROC curve was 0.803+/-0.039 (95% CI:
      0.727-0.878, P=0.000). Spearman's correlation coefficient analysis showed
      negative association of UA with C3 in SLE patients with LN (r=-0.356, P=0.002),
      but no association in those without LN. No correlations were found between UA and
      age, SLEDAI, CRP, IgG, IgM or IgA. Furthermore, analysis of covariance
      demonstrated that anti-Sm (beta=-0.218, P=0.004) and -U1RNP (beta=0.177, P=0.008)
      autoantibodies were independent determinants of serum UA. The UA level is
      independently associated with the development of LN in SLE patients.

PMID- 20155422
TI  - Intra-articular corticosteroid therapy for juvenile idiopathic arthritis: report
      of an experiential cohort and literature review.
AB  - The objective of the study to review an experiential cohort of patients receiving
      IACS and review the associated literature. Review of 121 IACS in 61 patients with
      JIA. At 3-month intervals, injected joints were evaluated for swelling and range
      of motion, and the patient and parent were questioned regarding associated pain
      and morning stiffness. Data were analyzed by log-rank analysis according to
      injected corticosteroid preparation and its dosage. Adverse events were also
      recorded. A thorough literature search was done for the literature review. Mean
      duration of response was 12.5 months (52% of joints in remission at 1 year, 20%
      after 2 years, and 7% after 3 years). Response was longer with at least 1 mg/kg
      of corticosteroid, with the longest responses seen with triamcinolone
      hexacetonide (THA)>triamcinolone acetonide>methylprednisolone. Adverse events
      were cutaneous atrophy at three injections sites (2.5%), and transient Cushingoid
      habitus and increased appetite in two patients (3%). Review of the literature
      generated similar responses to those included herein. Thus, there have been
      several recommendations for IACS to be a major JIA treatment, and surveys now
      demonstrate a high level of usage by pediatric rheumatologists. In conclusion the
      use of IACS in JIA substantiated. THA at a dose of 1-1.5 mg/kg is ideal.

PMID- 20155423
TI  - Late complications of newborn circumcision: a common and avoidable problem.
AB  - PURPOSE: The purpose of this paper is to study the types of operative and post
      operative late complications resulting from newborn circumcisions and to make
      recommendations to prevent them. METHODS: After obtaining IRB approval, a
      retrospective review of the late complications resulting from newborn
      circumcisions treated at the MassGeneral Hospital for Children from January 2003
      to December 2007 was undertaken. The source used was the consultation notes and
      operative reports of affected patients. Additionally, cases seen in the
      outpatient Pediatric Urology Clinic from April 2007 to April 2008 were reviewed.
      RESULTS: A total of 8,967 children were operated during the study period, of
      which 424 (4.7%) were for complications resulting from previous neonatal
      circumcision. Penile adhesions, skin bridges, meatal stenosis, redundant foreskin
      (incomplete circumcision with uncircumcised appearance), recurrent phimosis,
      buried penis and penile rotation were the most frequent complications. At the
      outpatient clinic of the Section of Pediatric Urology, 127 boys with concerns
      following newborn circumcision were evaluated, representing 7.4% of the total
      volume of cases seen in this clinic. CONCLUSIONS: Our results indicate the need
      to undertake a collaborative study to define the incidence of complications
      following newborn circumcisions, which should be performed by practitioners with
      adequate training in the technique of their choice and its post-operative care.

PMID- 20155425
TI  - Solid pseudopapillary neoplasm of the pancreas--proposed algorithms for diagnosis
      and surgical treatment.
AB  - PURPOSE: The incidence of solid pseudopapillary neoplasm (SPN) of the pancreas is
      rising. Although the evidence for proper management is accumulating, we still
      lack diagnostic and therapeutic guidelines. In this paper, therefore, we propose
      an algorithm for diagnosis and treatment of this rare type of tumor. METHODS: A
      literature search was carried out on "Medline" and "Pubmed" databases to identify
      studies investigating the clinicopathologic features, pathogenesis, diagnostic,
      and differential diagnostic pathways, and surgical and adjuvant treatment
      options. Evidence from relevant published literature was completed with data of
      six patients treated with SPN in our institution. RESULTS: This study included
      case series and retrospective reviews only, since no higher level of evidence
      exists in the relevant literature. The articles emphasized that preoperative
      diagnosis is desirable to set up a precise plan for surgical treatment. Further,
      an R0 organ-sparing resection for primary SPN and an en bloc resection of locally
      advanced SPN are advised, while resection of synchronous as well as metachronous
      distant metastases is strongly advocated for this rare type of pancreatic cancer.
      The role of adjuvant chemo- or radiotherapy still needs to be defined. Finally, a
      diagnostic and therapeutic algorithm is devised in this paper to aid proper
      management of SPN. CONCLUSION: Current recommendations for treatment of SPN of
      the pancreas rely mainly on case series as single institutional experiences and
      retrospective reviews. Although the level of evidence is relatively low, the way
      of management discussed above is likely to provide an excellent prognosis in
      typically young patients with SPN.

PMID- 20155424
TI  - Vascular pathology in the aged human brain.
AB  - Cerebral atherosclerosis (AS), small vessel disease (SVD), and cerebral amyloid
      angiopathy (CAA) are the most prevalent arterial disorders in the aged brain.
      Pathogenetically, AS and SVD share similar mechanisms: plasma protein leakage
      into the vessel wall, accumulation of lipid-containing macrophages, and fibrosis
      of the vessel wall. CAA, on the other hand, is characterized by the deposition of
      the amyloid beta-protein in the vessel wall. Despite these differences between
      CAA, AS and SVD, apolipoprotein E (apoE) is involved in all three disorders. Such
      a pathogenetic link may explain the correlations between AS, SVD, CAA, and
      Alzheimer's disease in the brains of elderly individuals reported in the
      literature. In addition, AS, SVD, and CAA can lead to tissue lesions such as
      hemorrhage and infarction. Moreover, intracerebral SVD leads to plasma protein
      leakage into the damaged vessel wall and into the perivascular space resulting in
      a blood-brain barrier (BBB) dysfunction. This SVD-related BBB dysfunction is
      considered to cause white matter lesions (WMLs) and lacunar infarcts. In this
      review, we demonstrate the relationship between AS, SVD, and CAA as well as their
      contribution to the development of vascular tissue lesions and we emphasize an
      important role for apoE in the pathogenesis of vessel disorders and vascular
      tissue lesions as well as for BBB dysfunction on WML and lacunar infarct
      development.

PMID- 20155426
TI  - Loss of SOCS3 expression is associated with an increased risk of recurrent
      disease in breast carcinoma.
AB  - PURPOSE: Constitutive activation of JAK/STAT pathway is observed in various solid
      tumors and hematological malignancies. SOCS3 acts as a key negative regulator of
      JAK/STAT pathway and represents one of the candidate tumor suppressor genes. In
      the current study, we aimed to evaluate SOCS3 expression in breast carcinoma and
      to explore the prognostic significance of SOCS3. METHODS: The expression of SOCS3
      was measured by Western blot and immunohistochemistry in breast carcinoma cells
      and a large cohort of tissue microarray, respectively. RESULTS: Among 367 human
      primary breast tumors, SOCS3 protein was detected in 103 patients. Deficient
      SOCS3 expression correlated significantly with lymph node metastasis (P = 0.003),
      blood vessel invasion (P = 0.029), VEGF (P = 0.001) and Ki-67 (P = 0.027).
      Univariate and multivariate analyses revealed that SOCS3 expression was an
      independent prognostic factor for disease-free survival (P < 0.0001). A positive
      SOCS3 protein expression correlated significantly with a low pSTAT3 protein
      expression in breast carcinoma (P = 0.015). The patients with a SOCS3 (+)/pSTAT3
      (-) phenotype had a better prognosis than any other combination (DFI: P < 0.0001,
      BCSS: P = 0.013). CONCLUSIONS: Deficient expression of SOCS3 is associated with
      an aggressive phenotype and portends a poor clinical outcome in breast carcinoma.

PMID- 20155427
TI  - Differential proteomic analysis of a highly metastatic variant of human breast
      cancer cells using two-dimensional differential gel electrophoresis.
AB  - Distant metastasis represents the major lethal cause of breast cancer. To
      understand the molecular mechanisms of breast cancer metastasis and identify
      markers with metastatic potential, we established a highly metastatic variant of
      parental MDA-MB-231 cells (MDA-MB-231HM). Using two-dimensional electrophoresis
      (2-DE), we performed a proteomic comparison of the two kinds of cells. As much as
      51 protein spots were differentially expressed between the selected variant and
      its parental counterpart in at least 3 experiments. Ten unique proteins were
      identified using matrix-assisted laser desorption/ionization-time of flight
      (MALDI-TOF) mass spectrometry (MS), liquid chromatography-electrospray ionization
      tandem mass spectrometry (LC-ESI-MS/MS), and database searching software. Among
      them, nine proteins were up-regulated in MDA-MB-231HM cells, including Macrophage
      capping protein (CapG), Galectin-1, Chloride intracellular channel protein 1,
      Endoplasmic reticulum protein ERp29 precursor, Stathmin-1 (STMN1), Isoform 1 of
      uridine-cytidine kinase 2(UCK2), Rho GDP-dissociation inhibitor 2 (ARHGDIB),
      isocitrate dehydrogenase [NADP] cytoplasmic (IDH1), and N-myc downstream
      regulated gene 1 (NDRG1) protein. Only transgelin-2 was down-regulated.
      Differential expression was confirmed for three proteins including CapG, STMN1,
      and transgelin-2 by Western blotting analysis. Transgelin-2 was chosen for
      further verification by immunohistochemistry. The results suggested that 2-DE
      would be an efficient way to screen the proteins responsible for specific
      biological function. Furthermore, the findings imply that different proteins may
      be involved in the metastatic process in breast carcinomas.

PMID- 20155428
TI  - Prediction of epidermal growth factor receptor mutations in the plasma/pleural
      effusion to efficacy of gefitinib treatment in advanced non-small cell lung
      cancer.
AB  - PURPOSE: Recently, mutations in the epidermal growth factor receptor (EGFR) gene
      were reported to correlate with EGFR tyrosine kinase inhibitor response in
      advanced non-small cell lung cancer (NSCLC). In this study, we attempted to
      detect EGFR mutations in plasma and pleural effusion samples and to make clear
      its correlations with gefitinib response and survival in NSCLC patients. METHODS:
      The free DNA was isolated from the plasma of 56 cases and pleural effusion of
      another 32 cases of advanced NSCLC. Five common types of EGFR mutations were
      analyzed by LightCycle PCR with Taqman-MGB probes. RESULTS: EGFR gene mutations
      were found in 22 of all the 88 (25%) NSCLC patients (23.2% of 56 plasma samples,
      28.1% of another 32 pleural effusion samples). EGFR mutations were more
      frequently present in females, never-smokers and adenocarcinomas (P < 0.01). It
      also showed that patients with EGFR mutations had a significantly better response
      rate when compared with that of the wild-type patients (P < 0.001). The median
      progression-free survival (11.2 vs. 2.7 months P = 0.005) and overall survival
      (21.8 vs. 5.8 months P = 0.003) were significantly higher in patients with EGFR
      mutations than in patients with wild-type EGFR. CONCLUSIONS: The EGFR mutations
      in the serum and the pleural effusion from advanced NSCLC patients can be
      detected with LightCycle PCR using Taqman-MGB probes. The mutations highly
      predict the efficacy of gefitinib in advanced NSCLC.

PMID- 20155429
TI  - Transcriptional regulation and functional implication of S100P in cancer.
AB  - S100P is an EF-hand calcium-binding protein that was originally identified in
      placenta and subsequently associated with cancer. It is a member of S100 family
      of proteins that function as extracellular and/or intracellular regulators of
      diverse cellular processes and participate in various human pathologies. S100P
      expression was detected in a spectrum of human tumor cell lines and tissues
      derived from breast, prostate, pancreas, lung and colon, where it was connected
      with malignant phenotype, hormone independence and resistance to chemotherapy.
      Overexpression of S100P was shown to promote tumorigenesis and metastasis in
      diverse cancer models. Functional studies of S100P indicate that its biological
      activities are exerted through extracellular signaling via RAGE receptor,
      resulting in increased proliferation and survival, or through intracellular
      interaction with ezrin, leading to increased cell migration and metastasis.
      Molecular mechanisms regulating expression of S100P in cancer cells are just
      emerging. Besides earlier described DNA methylation, recent studies implicate
      bone morphogenic protein and non-steroidal anti-inflammatory drugs in control of
      S100P expression during tumor progression. Functional analysis of S100P promoter
      identified SMAD, STAT/CREB and SP/KLF binding sites as key regulatory elements
      participating in transcriptional activation of S100P gene in cancer cells.
      Moreover, the most recent data reveal that expression of S100P is up-regulated by
      activation of glucocorticoid receptor suggesting that S100P could play a role in
      therapy resistance mediated by glucocorticoids in solid tumors. Elucidation of
      S100P regulation is an important step towards understanding biological
      significance of its tissue distribution and proposing strategies for targeted
      S100P modulation.

PMID- 20155430
TI  - Thermoanaerobacterium thermostercus sp. nov., a new anaerobic thermophilic
      hydrogen-producing bacterium from buffalo-dung.
AB  - A novel thermophilic, anaerobic, rod-shaped bacterium strain, designated Buff,
      was isolated from buffalo-dung samples collected from a buffalo-farm located in
      Caserta (Campania, south of Italy). Strain Buff was Gram-positive, motile and no
      spore-forming. The growth temperature range was 40-65 degrees C with an optimum
      at 60 degrees C, while pH growth range at 60 degrees C was 5.5-8.0 with an
      optimum at about pH 6.5. NaCl growth concentration ranged from 0 to 2.0% with an
      optimum at 0.5% (w/v); no growth was observed with the presence of NaCl 3.0%
      (w/v). The strain produced ethanol, acetate, lactate, H(2), H(2)S and CO(2) by
      glucose fermentation. The DNA G + C content was 34.4 mol%. As determined by 16S
      rRNA sequence analysis, this organism belonged to the genus
      Thermoanaerobacterium. On the basis of the physiological and molecular
      properties, we propose for strain Buff the new species designation
      Thermoanaerobacterium thermostercus sp. nov. This novel organism represents the
      first species of the genus Thermoanaerobacterium isolated from buffalo-dung. The
      type strain is Buff (=DSM 22141 = ATCC BAA-1776).

PMID- 20155431
TI  - Eighty-five redo surgeries after 733 laparoscopic treatments for ventral and
      incisional hernia: adhesion and recurrence analysis.
AB  - INTRODUCTION: This report reviews the clinical and functional outcomes of
      implanted meshes during a second-look evaluation of 85 cases after a large number
      (733) of laparoscopic incisional and ventral hernia repairs (LIVHR), of which 608
      were controlled throughout a period of 5 to 10 years. This report demonstrates a
      minimal occurrence of adhesions and a low rate of recurrences and other
      complications related to mesh usage. METHODS: Eighty-five re-operated cases after
      LIVHR were reviewed retrospectively. In every redo surgery, the first trocar was
      always inserted on a lateral side, external to the previous skin incisions of the
      transabdominal fixations. Mueller's adhesion scale was used to estimate adhesion
      severity (Mueller 0 indicates no adhesion; Mueller I indicates adhesion of the
      omentum; and Mueller II indicates serosal adhesions). The mechanism of recurrence
      is of paramount interest and is analyzed herein. If recurrence was observed, the
      defect was closed and a larger mesh of Parietex was implanted under the previous
      one, with transparietal fixation achieved by pulling the threads with the
      Endoclose device. RESULTS: In all of our "second-look" surgeries, the
      neoperitoneum perfectly covered the mesh. In 47.05% of the cases, we observed no
      adhesions (Mueller 0), 42.3% had adhesions of the omentum (Mueller I), and 10.58%
      had serosal adhesions (Mueller II). There was no shrinking or wrinkling of the
      prosthesis in any of the cases, confirming its total peritonization on the
      anterior abdominal wall. Within the first 3 years, only 4.1% of the controlled
      patients contracted recurrences, with a mean follow-up of 52 months. CONCLUSION:
      With the double-suturing technique used for LIVHR and the use of a composite
      mesh, we observed a low rate of recurrences and limited side effects as compared
      with the use of tacks intra-abdominally. Redo surgeries after LIVHR are feasible,
      but care must be taken due to unpredictable mesh adhesions.

PMID- 20155432
TI  - Successful treatment of severe nodular scleritis with adalimumab.
AB  - Ocular features may occur in longstanding rheumatoid arthritis. Among them,
      scleritis represents the most frequent manifestation of ophthalmologic rheumatoid
      disease. There are three types of anterior scleritis: diffuse, nodular, and
      necrotizing with and without inflammation (scleromalacia perforans). Nodular
      scleritis is the second cause of anterior scleritis representing 20% of all types
      of scleritis. The conventional treatment of nodular scleritis consists in topical
      steroids and DMARDS. In severe cases, the therapy with immunosuppressive agents
      to avoid complications is necessary. We describe a 46-year-old woman presented
      right nodular scleritis with rheumatoid arthritis. She was treated initially with
      topical steroids and DMARDs but was unable to received systemic steroids due to
      left open angle glaucoma in the opposite eye. After an ocular exacerbation, we
      initiated adalimumab with complete resolution of nodular scleritis. This is the
      first report of adalimumab in the treatment of nodular scleritis. Adalimumab
      could be a good alternative in patients with severe nodular scleritis who fail to
      have conventional treatment with DMARDs and unable to receive systemic steroids.

PMID- 20155433
TI  - Comparison of microscopy, two xenic culture techniques, conventional and real
      time PCR for the detection of Dientamoeba fragilis in clinical stool samples.
AB  - Dientamoeba fragilis is a pathogenic protozoan parasite that is notoriously
      difficult to diagnose. The aim of this study was to determine the gold standard
      for laboratory detection of D. fragilis. A total of 650 human faecal samples were
      included in the study. All specimens underwent the following: microscopy using a
      permanent stain (modified iron-haematoxylin), culture using a modified Boeck and
      Drbohlav's medium (MBD) and TYGM-9, a conventional polymerase chain reaction
      (PCR) and a real-time PCR (RT-PCR). The overall prevalence of D. fragilis in the
      study population was 5.4% (35/650). RT-PCR detected 35 isolates, conventional PCR
      detected 15 isolates, MBD culture detected 14 isolates, TYGM-9 detected ten
      isolates, while microscopy detected 12 isolates. RT-PCR detected an additional 15
      positive samples compared to the other diagnostic methods, all of which were
      confirmed by sequencing. When all methods were compared to each other, RT-PCR
      showed a sensitivity and specificity of 100 and 100%, conventional PCR 42.9 and
      100%, MBD culture 40 and 100%, TYGM-9 culture 28.6 and 100%, and microscopy 34.3
      and 99%, respectively. These results show that RT-PCR is the diagnostic method of
      choice for the detection of D. fragilis in clinical samples and, as such, should
      be considered as the gold standard for diagnosis.

PMID- 20155435
TI  - Construction of thrombus-targeted microbubbles carrying tissue plasminogen
      activator and their in vitro thrombolysis efficacy: a primary research.
AB  - Thrombosis is the common mechanism of various diseases of heart and vasculature
      and their major morbility and mortality. An efficient, safe and easy thrombolysis
      method is needed. We tried to develop a new type of ultrasound microbubbles
      carrying thrombolytics and simultaneously targeting to thrombus, which could bind
      with thrombus specifically and release the encapsulated drug locally under the
      ultrasound exposure. Microbubbles carrying tissue plasminogen activator (tPA) and
      Arg-Gly-Asp-Ser tetrapeptide (RGDS) were prepared by lyopyilization. Their
      properties were detected, including morphology, particle size, surface potential
      and pH. The results showed that the microbubbles were suitable for intravenous
      injection. The envelope rate of tPA, detected by ELISA, was (81.12 +/- 2.44%),
      and the conjugate rate of RGDS, detected by flow cytometer, was (94.49 +/-
      6.19%). The tPA encapsulated in microbubbles kept fibrinolysis activity under the
      conditions of both natural releasing and ultrasound exposure, checked by agarose
      fibrin plate process. The contrast-enhanced ultrasonography (CEU) in rabbit liver
      showed that they were good for enhanced ultrasound imaging. The in vitro
      thrombolysis of the microbubbles to the blood clots from healthy human was
      detected with a mimical flowing model propelled by peristaltic pump. The drug
      loaded microbubbles plus ultrasound irradiation got higher thrombolysis with the
      lowest dosage. The tPA-loaded microbubbles targeting to thrombus can be prepared
      by lyopyilization, which will bring out a novel way for the targeting drug
      released thrombolysis therapy.

PMID- 20155434
TI  - Prolonged ovalbumin challenge facilitates Th17 polarization in sensitized mice.
AB  - OBJECTIVE AND DESIGN: In this study, we explored whether prolonged ovalbumin
      (OVA) exposure in sensitized mice created an environment suitable for Th17
      differentiation. MATERIALS AND METHODS: BALB/c and C57BL/6 mice (n = 36), after
      intraperitoneal OVA sensitization on days 0 and 12, received prolonged OVA
      aerosol challenges up to day 55. Airway inflammatory cell levels, cytokine
      profiles, and Th17 cell infiltration were evaluated after sacrifice. RESULTS:
      Prolonged OVA challenge caused inflammation that was characterized by raised
      influxes of airway macrophages and neutrophils. Following long-term exposure,
      Th17 cytokines and Th17 cell numbers progressively increased in the lung (P <
      0.05) along with increased production of Th17 polarization-related factors,
      including TGF-beta, IL-6, and IL-23. The lineage-specific transcription factor
      for Th17 subsets, RORgammat, displayed similar upregulation throughout the OVA
      challenge (P < 0.05). CONCLUSIONS: Prolonged OVA challenge induces an environment
      that facilitates Th17 polarization.

PMID- 20155436
TI  - Human cytomegalovirus increases HUVEC sensitivity to thrombin and modulates
      expression of thrombin receptors.
AB  - Human cytomegalovirus (HCMV) establishes a life-long persistent infection. HCMV
      infection could be associated with chronic inflammatory diseases, such as
      cardiovascular disease and atherosclerosis. Here we observed that in HCMV (AD
      169) pre-exposed human umbilical vein endothelial cells (HUVEC), thrombin-induced
      expression of IL-1alpha and M-CSF is markedly enhanced compared to the un-exposed
      cells. Study of the expression of thrombin receptor genes in HUVEC showed that
      HCMV triggered a time- and concentration-dependent expression of the thrombin
      receptors PAR1, PAR3 and PAR4 at the mRNA level. Induction of PAR1 and PAR3 mRNA
      expression is due to transcriptional activation of their promoters as shown by
      gene reporter assay. Furthermore, the virus induced expression of PAR1 and PAR3
      but not PAR4 proteins, as analyzed by Western immunoblotting. However, flow
      cytometric analysis revealed that only PAR3, expressed at very low level in
      control HUVEC, is induced at the surface during the exposure to the virus. Our
      data suggest that although exposure to HCMV induces a minor increase of cell
      surface receptors expression, it does make endothelial cells more responsive to
      additional thrombin stimulation.

PMID- 20155437
TI  - Discrimination and evaluation of lactoferrin and delta-lactoferrin gene
      expression levels in cancer cells and under inflammatory stimuli using TaqMan
      real-time PCR.
AB  - The lactoferrin gene is known to be expressed either constitutively or under
      inducible conditions such as hormonal stimuli or inflammation. Its transcription
      from alternative promoters leads to two products, lactoferrin (Lf) and delta
      lactoferrin (DeltaLf) mRNAs the expressions of which are altered during
      oncogenesis. The comparison of the two enhancer/promoter regions revealed that
      the two isoforms might be differentially trans-activated. Nevertheless,
      concomitant expression of both transcripts has been found in some normal tissues
      and in a subset of breast cancer cell lines and biopsies. Moreover, we found
      putative inflammatory response elements in both P1 and P2 promoter regions
      suggesting that both Lf and DeltaLf might be upregulated under inflammatory
      stimuli. Therefore, a duplex Taqman gene expression assay has been developed and
      used to profile mRNA expression of the Lf gene in the case of cancer and under
      inflammatory conditions. Discrimination between the two transcripts is achieved
      by using a primer pairs/probe set within exon 1beta for DeltaLf and a primer
      pairs/probe set within exon 1 and exon 2 for Lf. In this study, we confirmed that
      Lf/DeltaLf Taqman gene expression assay is a powerful tool to investigate the
      expression of both Lf and DeltaLf transcripts. We also showed that lymphocytes
      and leukocytes isolated from fresh human blood expressed an extremely high level
      of DeltaLf messengers. An extensive series of cancer cell lines has been studied
      confirming that both P1 and P2 promoter regions of the Lf gene are downregulated
      or silenced in the case of cancer. Furthermore, using stimulation by bacterial
      lipopolysaccharides (LPS), we showed that in MDA-MB-231 and HT-29 epithelial
      cells, Lf expression is strongly increased with a higher expression level in MDA
      MB-231 whereas DeltaLf expression is not. These results suggest that the NF
      kappaB/cRel response elements present in the P1 promoter region are functional
      whereas those present in the P2 promoter region are not and show that DeltaLf is
      not regulated in inflammatory conditions.

PMID- 20155438
TI  - Periodontitis, periodontopathic bacteria and lactoferrin.
AB  - Lactoferrin (LF) is a component of saliva and is suspected to be a defense factor
      against oral pathogens including Streptococcus mutans and Candida albicans.
      Periodontitis is a very common oral disease caused by periodontopathic bacteria.
      Antimicrobial activities and other biological effects of LF against
      representative periodontopathic bacteria, Aggregatibacter actinomycetemcomitans,
      Porphyromonas gingivalis, and Prevotella intermedia, have been widely studied.
      Association of polymorphisms in LF with incidence of aggressive periodontitis and
      the role of LF in the gingival crevicular fluid as a marker of periodontitis
      severity have also been reported. Periodontopathic bacteria reside as a biofilm
      in supragingival and subgingival plaque. Our recent study indicated that LF
      exhibits antibacterial activity against planktonic forms of P. gingivalis and P.
      intermedia at higher concentrations, and furthermore, LF effectively inhibits
      biofilm formation and reduces the established biofilm of these bacteria at
      physiological concentrations. A small-scale clinical study indicated that oral
      administration of bovine LF reduces P. gingivalis and P. intermedia in the
      subgingival plaque of chronic periodontitis patients. LF seems to be a biofilm
      inhibitor of periodontopathic bacteria in vitro and in vivo.

PMID- 20155439
TI  - Prediction of 60 day case-fatality after aneurysmal subarachnoid haemorrhage:
      results from the International Subarachnoid Aneurysm Trial (ISAT).
AB  - Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with
      substantial case-fatality. Our purpose was to examine which clinical and neuro
      imaging characteristics, available on admission, predict 60 day case-fatality in
      aSAH and to evaluate performance of our prediction model. We performed a
      secondary analysis of patients enrolled in the International Subarachnoid
      Aneurysm Trial (ISAT), a randomised multicentre trial to compare coiling with
      clipping in aSAH patients. Multivariable logistic regression analysis was used to
      develop a prognostic model to estimate the risk of dying within 60 days from aSAH
      based on clinical and neuro-imaging characteristics. The model was internally
      validated with bootstrapping techniques. The study population comprised of 2,128
      patients who had been randomised to either endovascular coiling or neurosurgical
      clipping. In this population 153 patients (7.2%) died within 60 days. World
      Federation of Neurosurgical Societies (WFNS) grade was the most important
      predictor of case-fatality, followed by age, lumen size of the aneurysm and
      Fisher grade. The model discriminated reasonably between those who died within 60
      days and those who survived (c statistic = 0.73), with minor optimism according
      to bootstrap re-sampling (optimism corrected c statistic = 0.70). Several strong
      predictors are available to predict 60 day case-fatality in aSAH patients who
      survived the early stage up till a treatment decision; after external validation
      these predictors could eventually be used in clinical decision making.

PMID- 20155442
TI  - Maternal morbidity and perinatal outcomes among foreign-born Cambodian, Laotian,
      and Vietnamese Americans in Washington State, 1993-2006.
AB  - This study examined differences in perinatal outcomes of Southeast Asian (SEA)
      women compared with non-Hispanic white women in Washington. Using linked birth
      certificate and hospitalization discharge records for the years 1993-2006, we
      compared singleton births of Cambodian (3,858), Laotian (2,223), and Vietnamese
      (12,949) women with a random sample of white women (35,581). Associations between
      maternal nativity and perinatal outcomes were assessed using multivariable
      logistic regression. There are clear nativity differences among SEAs for
      gestational diabetes mellitus, anemia, placenta previa and febrile illness. SEAs
      had increased risks for these disorders when compared with white women. Compared
      with infants delivered of white women, infants of SEAs had increased risks for
      moderate to heavy meconium, birth injury and low birth weight. Differences in
      nativity among SEAs (populations that are traditionally studied in aggregate)
      should be considered when designing and carrying out interventions to prevent
      adverse pregnancy morbidity and outcomes among immigrants.

PMID- 20155443
TI  - Prognostic value of dobutamine stress echocardiography in diabetic patients.
AB  - CAD is the main cause of morbidity and mortality in diabetic patients; we need
      reliable clinical parameters to stratify cardiovascular risk in these patients.
      We thus assessed prognostic value of clinical parameters, rest and stress
      echocardiographic data in diabetic patients, with known or suspected CAD. We
      studied 322 type 2 diabetic patients, who underwent dobutamine stress
      echocardiography (DSE) for known or suspected CAD; for prognostic assessment, end
      points were all-cause mortality and hard cardiac events (cardiac death and non
      fatal myocardial infarction). During DSE, viability and inducible ischemia
      developed in 65 (20%) and 192 (60%) subjects, respectively; a severe ischemia (an
      asynergic area including more than 40% of all segments combined with a rate
      pressure product < 17,000) appeared in 88 (27%). Presence of a diabetic treatment
      or microvascular diabetic complications didn't influence prognosis, while a
      longer diabetes duration was associated with a higher all-cause mortality at
      univariate analysis. At multivariate analysis, an advanced age (RR = 1.108, CI:
      1.039-1.182, P = 0.002), a lower left ventricular ejection fraction (RR = 0.956,
      CI: 0.919-0.994, P = 0.025) and, tendentially, peripheral vascular disease (RR =
      2.942, CI: 0.985-8.785, P = 0.053) independently determined an increased all
      cause mortality. New hard cardiac events occurred more frequently in presence of
      peripheral vascular disease (RR = 2.975, CI: 1.339-6.608, P = 0.007), viability
      (RR = 3.427, CI: 1.400-8.390, P = 0.007) and severe ischemia (RR = 3.245, CI:
      1.503-7.005, P = 0.003). In diabetic patients with known or suspected CAD,
      presence of viability and severe ischemia during DSE are independently associated
      with higher occurrence of hard cardiac events.

PMID- 20155444
TI  - Hydrophobicity-related protein contents and surface areas of aerial conidia are
      useful traits for formulation design of fungal biocontrol agents.
AB  - To clarify the potential use of hydrophobicity-related traits of aerial conidia
      in formulation design of fungal biocontrol agents, hydrophobicity rates (H (r))
      and surface areas (S (a)) of aerial conidia were assessed with 48 strains of
      Beauveria bassiana, Isaria fumosorosea and Metarhizium spp. Inter- or intra
      specific variation was large in H (r) (59.7-92.2%) and S (a) (7.9-25.3 microm(2)
      conidium(-1)) measurements, which were significantly correlated (r (2) = 0.55).
      Six isolates of the three fungi with distinguished H (r) and S (a) were further
      studied. Conidial wall proteins of these isolates were sequentially extracted
      with sodium dodecyl sulfate (SDS), formic acid (FA) and trifluoroacetic acid
      (TFA). Their H (r) values were significantly correlated to the contents (P (c))
      of TFA-soluble, but FA-insoluble, proteins (2.7-44.8 microg per 10(7) conidia; r
      (2) = 0.79) and reduced drastically by the FA/TFA treatments, which eliminated
      the hydrophobin-based rodlet layers of conidial surfaces. However, the SDS
      treatments had no effect on either H (r) or rodlet layers. The dispersancy of a
      tested emulsifier to oil formulations of the six isolates in water was adversely
      correlated to their H (r) (r (2) = 0.94). The results indicate that both P (c)
      and S (a) are inherent hydrophobicity-related traits and can be utilized to
      select fungal biocontrol candidates for improved formulation and application.

PMID- 20155445
TI  - Effects of carbon concentrations and carbon to nitrogen ratios on sporulation of
      two biological control fungi as determined by different culture methods.
AB  - The nematophagous fungus Pochonia chlamydosporia (Clavicipitaceae) and
      entomopathogenic fungus Beauveria bassiana (Cordycipitaceae) have great potential
      for biological control. However, a significant barrier to their commercial
      development as mycopesticides is the high costs associated with production.
      Carbon (C) concentration and C to nitrogen ratio (C:N ratio) greatly affect
      fungal growth and sporulation. Effects of C concentration and C:N ratio differed
      when the fungi were cultivated using two different methods: the conventional
      (continuous cultivation) method and a novel "two-stage" method. Sporulation of P.
      chlamydosporia (HSY-12-14) was the highest when the media contained 6 g l(-1) C
      and a C:N ratio of 40:1 or 8 g l(-1) C and C:N ratios of 20:1 or 40:1 for the
      conventional method but 8 g l(-1) C and a C:N ratio of only 10:1 with the novel
      "two-stage" method. Sporulation of B. bassiana (IBC1201) was the highest when the
      media contained 12 g l(-1) C and a C:N ratio of 40:1 with the conventional method
      but only 4 g l(-1) C and a C:N ratio of 5:1 with the novel "two-stage" method. In
      addition, the nutritional requirements as determined by the conventional method
      differed for mycelial growth and sporulation. Understanding the effects of
      nutrition on sporulation can help programs seeking to use these organisms as
      biological control agents and is essential for their mass production and
      commercialization.

PMID- 20155446
TI  - Mercury(II) biosorption using Lessonia sp. kelp.
AB  - Lessonia nigrescens and Lessonia trabeculata kelps have been tested for the
      sorption of mercury from aqueous solutions. A pretreatment (using CaCl(2))
      allowed stabilizing the biomass that was very efficient for removing Hg(II) at pH
      6-7. Sorption isotherms were described by the Langmuir equation with sorption
      capacities close to 240-270 mg Hg g(-1) at pH 6. The temperature had a negligible
      effect on the distribution of the metal at equilibrium. The presence of chloride
      anions had a more marked limiting impact than sulfate and nitrate anions. The
      uptake kinetics were modeled using the pseudo-second-order equation that fitted
      better experimental data than the pseudo-first-order equation. The particle size
      hardly influenced sorption isotherms and uptake kinetics, indicating that
      sorption occurs in the whole mass of the biosorbent and that intraparticle mass
      transfer resistance was not the limiting rate. Varying the sorbent dosage and the
      initial metal concentration influenced the equilibrium, but the kinetic
      parameters were not drastically modified. Metal can be eluted with hydrochloric
      acid, citric acid, or acidic KI solutions.

PMID- 20155447
TI  - Melatonin protects N2a against ischemia/reperfusion injury through autophagy
      enhancement.
AB  - Researches have shown that melatonin is neuroprotectant in ischemia/reperfusion
      mediated injury. Although melatonin is known as an effective antioxidant, the
      mechanism of the protection cannot be explained merely by antioxidation. This
      study was devoted to explore other existing mechanisms by investigating whether
      melatonin protects ischemia/reperfusion-injured neurons through elevating
      autophagy, since autophagy has been frequently suggested to play a crucial role
      in neuron survival. To find it out, an ischemia/reperfusion model in N2a cells
      was established for examinations. The results showed that autophagy was
      significantly enhanced in N2a cells treated with melatonin at reperfusion onset
      following ischemia and greatly promoted cell survival, while autophagy blockage
      by 3-MA led to the shortened N2a cell survival as assessed by MTT, transmission
      electron microscopy, and laser confocal scanning microscopy. Besides, the protein
      levels of LC3II and Beclin1 were remarkably increased in ischemia/reperfusion
      injured N2a in the presence of melatonin, whereas the expression of p-PKB, key
      kinase in PI3K/PKB signaling pathway, showed a decrease when compared with
      untreated subjects as accessed by immunoblotting. Taken together these data
      suggest that autophagy is possibly one of the mechanisms underlying
      neuroprotection of melatonin.

PMID- 20155448
TI  - Construction and identification of a yeast two-hybrid bait vector and its effect
      on the growth of yeast cells and the self-activating function of reporter genes
      for screening of HPV18 E6-interacting protein.
AB  - By using a yeast two-hybrid system, a yeast two-hybrid bait vector was
      constructed and identified for screening of the HPV18 E6-interacting proteins,
      and its effects on the growth of yeast cells and the activation of reporter genes
      were investigated. Total mRNA extracted from Hela cells was reversely transcribed
      into cDNA. Fragment of HPV18 E6 cDNA was amplified using RT-PCR and directly
      ligated to the pGBKT7 vector. The recombinant plasmid was confirmed by
      restriction endonuclease analysis and DNA sequencing. The recombinant pGBKT7
      HPV18 E6 plasmid and empty pGBKT7 vector were transformed into the yeast cell
      AH109, respectively. After they were cultured respectively in YPDA liquid medium
      and nutrition-deficient culture medium, their toxicity and transcriptional
      activation were tested by both the phenotype assay and the color assay. The bait
      plasmid HPV18 E6 was successfully obtained. After being cultured in YPDA liquid
      medium for 16h, the A (600 nm) values of two yeast fluids were 0.98+/-0.03 and
      0.99+/-0.02, respectively. The recombinant pGBKT7-HPV18 E6 plasmid and empty
      pGBKT7 vector could grow to white colonies on SD/-Trp/X-alpha-gal plates, while
      no colony could survive on SD/-His/-Trp/X-alpha-gal, SD/-Ade/-Trp/X-alpha-gal
      plates, indicating that the bait plasmid pGBKT7-HPV18 E6 was constructed
      successfully and expressed correctly, and could not activate the transcription of
      reporter gene alone. The yeast two-hybrid GAL4 system 3 can be utilized to find
      HPV18 E6 interacting proteins.

PMID- 20155449
TI  - Identification of common variants within KCNK17 in Chinese Han population.
AB  - KCNK17 is a member of the acid-sensitive subfamily of tandem pore K(+) channels,
      which are open at all membrane potentials an red contribute to cellular resting
      membrane potential. Recent genome-wide study (GWA) has shown that variants within
      KCNK17 confer genetic susceptibility for increasing ischemic stroke. In an effort
      to discover additional polymorphism(s), we scrutinized the genetic polymorphisms
      in the KCNK17. By direct DNA sequencing in 32 individuals, we identified nine
      sequence variants within the 16 kb of whole KCNK17 gene: one in exon1, one in
      intron and seven in the promoter region. Haplotypes, their frequencies and
      linkage disequilibrium coefficients (D'), among polymorphisms were estimated. All
      the polymorphisms in the 5'-flanking region (SNP2-SNP7) being in complete (or
      nearly complete) association with each other in the promoter region maybe produce
      synergistic effect to regulate the expression of KCNK17 gene and then have an
      influence on the pathogenesis of cerebrovascular diseases. The common haplotypes
      were observed comprising 88.9% of the total haplotypes in the same block.
      Bioinformatic analysis predicted several potential transcriptional factors
      binding sites by SNP -95, -134, -596 and -846. However, these binding sites need
      to be experimentally verified. The information concerning genetic polymorphisms
      of KCNK17 gene might provide valuable information for future genetic studies of
      diseases.

PMID- 20155450
TI  - Isolation of cultured endothelial progenitor cells in vitro from PBMCs and
      CD133(+) enriched cells.
AB  - Two isolation methods for sorting of endothelial progenitor cells (EPCs): from
      peripheral blood mononuclear cells (PBMCs) and CD133(+) enriched cells were
      compared, by defining the cell morphology, phenotype, reproductive activities and
      function in vitro, to provide a reference for clinical application of EPCs. PBMCs
      from healthy subjects were used either directly for cell culture or for CD133(+)
      sorting. The two groups of cells were cultured in complete medium 199 (M199) for
      7 to 14 days and the phenotypes of EPCs were analyzed by FACS. The proliferation
      of differentiated EPCs was studied by MTT assay, and the VEGF concentration was
      measured using an ELISA kit. ECM gel experiment and migration assay were
      performed in vivo. The results showed that PBMCs produced more colony-forming
      units (CFU) than CD133(+) enriched cells from the same volume of blood (P<0.01).
      From day 7 to 14, the two groups showed decreased expression of hematopoietic
      stem cell markers and increased level of endothelial markers, but CD144(+) cells
      in CD133(+) group were less than in PBMCs group (P<0.01). PBMCs group secreted
      more VEGF than CD133(+) group on the day 7 (P<0.01). As compared with CD133(+)
      group, PBMCs group had more potent potential of proliferation and vascularization
      in vitro. It was concluded that CD133(+) sorted cells showed a lower capacity of
      differentiation, secretion, proliferation and vascularization in vitro,
      suggesting that CD133-negative cells may be a preferential way to get EPCs for
      clinical therapy.

PMID- 20155451
TI  - Anti-tumor angiogenesis with a recombinant ag43/FGFR1 chimeric protein as a model
      antigen.
AB  - In order to investigate the anti-tumor angiogenesis activity with a recombinant
      Ag43/FGFR1 chimeric protein (AF) vaccine in a mouse H22 hepatoma model, tumor
      volume and survival rate of the mice were studied at a 3-day interval.
      Microvessel density (MVD) was detected by immunohistochemistry. The endothelial
      deposition of autoantibodies within tumor tissues was examined by
      immunofluorescent staining, and anti-FGFR1 antibody-producing B cells (APBCs)
      were tested by enzyme-linked immunospot (ELISPOT) assay. Compared with the three
      control groups, the tumor volume was significantly decreased and the survival
      time was significantly prolonged in AF-immunized group (P<0.05). The number of
      APBCs in AF-immunized mice (129.6+/-10.9) was more than in controls [6.2+/-1.1
      (FGFR1), 6.0+/-1.2 (Ag43) and 5.2+/-1.4 (NS), P<0.01]. Moreover, the endothelial
      deposition of autoantibodies was found in tumor tissues from AF-immunized mice,
      but not in control groups. MVD in AF-immunized group was significantly lower than
      in FGFR1-immunized group, Ag43-immunized group and NS group (10.3+/-3.1 vs 39.4+/
      8.6 vs 42.3+/-9.8 and 43.6+/-10.6, P<0.01). These findings demonstrated that the
      AF protein vaccine effectively inhibited tumor angiogenesis and growth via
      production of autoantibodies against self-FGFR1.

PMID- 20155452
TI  - Focal cerebral ischemia induces Alzheimer's disease-like pathological change in
      rats.
AB  - The changes in the tau protein phosphorylation and expression of bcl-2, and bax
      in rat parietal cortex neurons after focal cerebral ischemia-reperfusion (I/R)
      were explored, and the relationship between the tau protein phosphorylation and
      the expression of bax or apoptosis was clarified in order to elucidate the
      relationship between cerebral infarction and Alzheimer's disease. The rat focal
      cerebral I/R model was induced by occlusion of the right middle cerebral artery
      using the intraluminal suture method. The level of tau protein phosphorylation at
      Ser396, Ser404, Tyr231, Ser199/202 sites and the expression of bcl-2, bax and
      total tau 5 in rat parietal cortex during focal cerebral ischemia/reperfusion
      were detected by Western blot. The relationship between the tau protein
      phosphorylation and the expression of bax, or apoptosis was examined by TUNEL
      method and double-labeling immunofluorenscence method. The results showed that
      the level of tau hyperphosphorylation at Ser199 / 202, Ser396, Ser404, Tyr231
      sites and the expression levels of bcl-2, and bax were significantly higher in
      I/R group than in the sham group, but the ratio of bcl-2/bax was decreased.
      Neuronal apoptosis, bax expression and the tau protein hyperphosphorylation were
      co-localized. It is suggested that Alzheimer's disease-like pathological changes
      occur after cerebral I/R. The highly abnormal phosphorylation of tau protein
      plays a key role in cerebral I/R-induced apoptosis. The cerebral infarction may
      contribute to Alzheimer's disease occurrence and development.

PMID- 20155453
TI  - Proliferation and apoptosis of bone marrow CD4(+) T cells in patients with
      aplastic anemia and impacts of the secreted cytokines on hematopoietic stem cells
      from umbilical cord blood.
AB  - Recent studies indicate that immune-associated aplastic anemia (AA) resembles
      such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune
      thyroiditis that belong to organ-specific autoimmune diseases. Many independent
      investigation groups have successfully isolated the pathopoiesis-associated T
      cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral
      blood and bone marrow (BM) in AA patients. In the current study, BM CD4(+) T
      cells were isolated from AA patients and healthy controls with immunomagnetic
      beads sorting, and proliferation capability, apoptosis features and the impacts
      of their secreted cytokines on hematopoiesis stem/progenitor cells were compared
      between them. By (3)H-TdR method, CD4(+) T cells in AA group presented more
      enhanced proliferative activity. The stimulation index in control group and AA
      group was 1.47+/-0.24, and 2.51+/-0.34 respectively (P<0.01). After BM CD4(+) T
      cells were induced by high concentration of CD3 monoclonal antibody for 18 h,
      evident apoptosis cells could be seen under the electron microscope in both
      control group and AA group. Flow cytometry revealed that apoptosis rates in the
      early and late stages of AA group were significantly higher than in control group
      (P<0.01). Early-stage apoptosis rate in control and AA groups was (6.85+/-1.48)%
      and (16.98+/-4.40)%, and late-stage apoptosis rate in control group and AA group
      was (2.65+/-1.57)% and (7.74+/-0.83)%, respectively (P<0.01). The CFU-GM count in
      AA group and control group was (74.50+/-9.50)/10(4) cells and (124.25+/
      19.80)/10(4) cells respectively under an inverted microscope (P<0.01), and the
      expression levels of CyclinD3 mRNA and protein in cord blood CD34(+) cells were
      both down-regulated induced by BM CD4(+) T cell culture supernatant in AA
      patients. These results indicate that BM CD4(+) T cells of AA patients are likely
      in an abnormally proliferative, and activated state which can correlate
      intimately with AA hematopoiesis damage. BM CD4(+) T cells in AA patients can
      secret some soluble cytokines that can inhibit proliferation of hematopoietic
      stem cells by suppressing the expression of Cyclin D3, resulting in hematopoiesis
      failure.

PMID- 20155454
TI  - Binding of EGF1 domain peptide in coagulation factor VII with tissue factor and
      its implications for the triggering of coagulation.
AB  - The binding function of EGF1 domain peptide with tissue factor (TF) and its
      ability of triggering coagulation were explored. The TF expression model in vitro
      was established by lipopolysaccharide induction. The affinity of EGFP-EGF1 and TF
      expressing cells was analyzed by fluorescence microscopy and flow cytometry
      (FCM). The affinity of EGFP-EGF1 and rat soluble TF was quantitated by surface
      plasmon resonance (SPR). The ability of EGFP-EGF1 in triggering coagulation was
      tested by prothrombin time assay. The FCM results showed recombinant factor VII
      (rFVII) could definitely depress the integration of EGFP-EGF1 with recombinant TF
      (rTF) (68.65%+/-3.86% vs 57.98%+/-4.71%, P<0.01). The SPR results indicated the
      association constant ka of EGFP-EGF1 proteins was higher than rFVII (8.29+/-1.39
      vs 3.75+/-0.32, P<0.01). However, the EGFP-EGF1 protein lost the activity of
      triggering coagulation as compared with blood plasma of normal SD rats (56.8+/
      3.2 s vs 17.8+/-3.4 s, P<0.01). It was concluded that the rat EGF1 peptide could
      specifically bind to TF without the ability of triggering coagulation. EGF1
      peptide may be a good target head for delivering drugs to TF in anticoagulation
      therapy.

PMID- 20155455
TI  - Effects and mechanism of irbesartan on tubulointerstitial fibrosis in 5/6
      nephrectomized rats.
AB  - Tubulointerstitial fibrosis (TIF) is a common pathological feature of end-stage
      kidney disease. Previous studies showed that upregulation of TGFbeta1 notably
      contributed to the chronic renal injury and irbesartan halted the development of
      TIF in rats with 5/6 renal mass reduction. This study was to investigate the
      effects of irbesartan on chronic TIF and the mechanism involved TGFbeta1 in the
      rodent model of chronic renal failure involving 5/6 nephrectomy. The results
      showed that irbesartan significantly attenuated the rise in blood pressure and
      tubulointerstitial injury observed in this model. Masson staining of the renal
      tissue revealed that there appeared severe renal tubule atrophy and fibrosis in
      operation group, but the lesion was attenuated mostly in irbesartan-treated
      group. Immunohistochemistry showed that irbesartan treatment apparently decreased
      the protein expression of TGFbeta1 which was up-regulated in operation groups.
      Western blot showed that irbesartan treatment down-regulated the expression of
      TGFbeta1, phosphorylated smad2 (p-smad2), AT1R and phosphorylated p38 (p-p38)
      MAPK, but significantly up-regulated the protein expression of smad6 as compared
      with operation group. These findings suggest that irbesartan attenuates
      hypertension and reduces the development of TIF in rats with 5/6 renal mass
      reduction via changes in the expression of these proteins at least including
      smad6, TGF-beta1, p-smad2, AT1 and p-p38 MAPK.

PMID- 20155456
TI  - Reduction in bile acid pool causes delayed liver regeneration accompanied by down
      regulated expression of FXR and c-Jun mRNA in rats.
AB  - The present study attempted to examine the effects of bile acid pool size on
      liver regeneration after hepatectomy. The rats were fed on 0.2% cholic acid (CA)
      or 2% cholestyramine for 7 days to induce a change in the bile acid size, and
      then a partial hepatectomy (PH) was performed. Rats fed on the normal diet served
      as the controls. Measurements were made on the rate of liver regeneration, the
      labeling indices of PCNA, the plasma total bile acids (TBA), and the mRNA
      expression of cholesterol 7alpha-hydroxylase (CYP7A1), farnesoid X receptor
      (FXR), and transcription factor c-Jun or c-fos. As compared with the normal and
      CA groups, the rate of liver regeneration was decreased on the day 3, and 7 after
      PH; the peak of the labeling indices of PCNA was delayed and the labeling indices
      were significantly reduced on the day 1; the TBA were also decreased on the day
      1; the expression of FXR decreased but that of CYP7A1 increased at any given
      time; at the 1st, and 3rd h, the expression of c-Jun was declined in the
      cholestyramine group. The reduction in the bile acid pool size was found to delay
      the liver regeneration, which may be caused by the down-regulation of FXR and c
      Jun expression.

PMID- 20155457
TI  - Influence of osteopontin short hairpin RNA on the proliferation and invasion of
      human renal cancer cells.
AB  - The influence of short hairpin RNA (shRNA)-mediated osteopontin (OPN) gene
      silencing on the proliferation and invasion of human renal cancer ACHN cells was
      investigated. Four types of OPN shRNA recombinant plasmids were constructed and
      RT-PCR assays were used to screen the most highly functional shRNA recombinant
      plasmids, which were transferred into the cultured ACHN cells by Lipofectamine
      2000. The cells transfected by shRNA expression vectors (ACHN/OPN) were
      visualized under an inverted microscope and screened by G418. Untreated cells
      (ACHN) and cells transfected by mock vectors (ACHN/Vect) were used as control
      groups. The expression levels of OPN mRNA and protein were detected by real-time
      PCR and Western blot respectively. The cell cycle and ratios of apoptotic cells
      were assessed by flow cytometry. MTT method was used for drawing the growth curve
      and observing cell proliferation in vitro. The abilities of migration and
      invasion in three groups were measured by Transwell chamber test. The expression
      levels of matrix metalloproteinase (MMP)-2 and MMP-9 in three groups were
      examined by Western blot. Our results showed that the recombinant plasmid could
      be successfully transferred into ACHN cells by Lipofectamine 2000. Compared with
      untreated cells, the expression levels of OPN mRNA and protein in ACHN/OPN cells
      were decreased by 59.68% and 76.42%, respectively (P<0.05), ACHN/OPN cells were
      blocked in S phase and apoptotic ratio increased significantly (P<0.05), however,
      no significant differences were found between ACHN/Vect and ACHN. Recombinant
      plasmid significantly attenuated expression levels of MMP-2 and MMP-9 proteins
      and suppressed the proliferation, migration, and invasion of ACHN cells. This
      study suggested that OPN may play an important role in the growth and invasion of
      human renal cancer ACHN cells, and these processes are correlated with the
      activations of MMP-2 and MMP-9. Our data provided preliminary experimental
      evidence for the feasibility of RNA interference technology in gene therapy of
      human renal cancer.

PMID- 20155458
TI  - Epigenetic regulation of the ERbeta gene on the estrogen signal transfection
      pathway in colon cancer cells.
AB  - We studied the regulatory effects of the estragen receptorbeta (ERbeta) gene on
      the downstream estrogen signal transfection pathway in colon cancer cells and the
      possible mechanisms involved. A human ERbeta gene recombinant expression plasmid,
      pEGFP-C1-ERbeta, was constructed and transfected into the Caco-2 colon cancer
      cell line, a line with low ERbeta gene expression. The expression of ERbeta mRNA
      and protein was detected 72 h after transfection. RT-PCR was used to examine the
      expression levels of the progesterone recepror (PR) gene containing the classic
      estrogen response element (ERE), the C-fos oncogene containing the AP-1 site (a
      non-classical ER binding site), the epigenetic modifying genes, such as Dnmt1,
      Dnmt3a, Dnmt3b, and histone methyltransferase (HMT), and the human mismatch
      repair gene hMLH1. Methylation-specific PCR was used to detect the changes in the
      methylated sites of the CpG islands in the promoters of the ERbeta, PR, and C-fos
      genes. The results indicated that the human ERbeta gene recombinant expression
      plasmid pEGFP-C1-ERbeta was successfully constructed and transfected into Caco-2
      cells. As compared with the control group, the mRNA and protein expression of
      ERbeta gene was increased significantly 72 h after the transfection of pEGFP-C1
      ERbeta into the Caco-2 cells. As compared with the control group, the mRNA
      expression of the PR, C-fos, Dnmt3a and Dnmt3b genes was increased significantly
      72 h after the transfection of pEGFP-C1-ERbeta into the Caco-2 cells, but the
      mRNA expression of the Dnmt1, HMT, and hMLH1 genes decreased significantly
      (P<0.05). As compared with the control group, different degrees of demethylation
      occurred in the promoters of the ERbeta, progesterone receptor (PR), and C-fos
      oncogene 72 h after the transfection of pEGFP-C1-ERbeta into the Caco-2 cells.
      The methylation index of the estrogen signal transfection pathway in Caco-2 cells
      was decreased significantly following the expression restoration of ERbeta gene
      (P<0.05). It is concluded that the restoration or up-regulation of the ERbeta
      gene in Caco-2 cells may significantly activate the expression of the related
      target genes in the downstream estrogen signal transfection pathway and may
      result in the demethylation changes of the pathway. During the process, the
      expression level and activity of the epigenetic modifying genes and the human
      mismatch repair gene have changed simultaneously. The regulatory effect of the
      ERbeta gene on the estrogen signal transfection pathway to a certain extent
      partly involves demethylation.

PMID- 20155459
TI  - Neurogenic differentiation of murine adipose derived stem cells transfected with
      EGFP in vitro.
AB  - Some studies indicate that adipose derived stem cells (ADSCs) can differentiate
      into adipogenic, chondrogenic, myogenic, and osteogenic cells in vitro. However,
      whether ADSCs can be induced to differentiate into neural cells in vitro has not
      been clearly demonstrated. In this study, the ADSCs isolated from the murine
      adipose tissue were cultured and transfected with the EGFP gene, and then the
      cells were induced for neural differentiation. The morphology of those ADSCs
      began to change within two days which developed into characteristics of round
      cell bodies with several branching extensions, concomitantly expressing EGFP
      fluorescence. Approximately 60% of the total cell populations were bipolar or
      multipolar in shape. Some of them appeared to make contact with their neighboring
      cells. RT-PCR, Western blot and Immunocytochemistry revealed that the expression
      levels of the markers of neurons and oligodendrocytes such as MAP2, NF-70, Neu N
      and RIP upon neural induction were increased, but the expression of the special
      marker of astrocytes, GFAP, was undetectable until 96 h after induction when a
      small signal was observed. It was concluded that the ADSCs transfected with EGFP
      possessed the ability to undergo morphologic and phenotypic changes consistent
      with neural differentiation in vitro. It suggests that these cells might provide
      an ideal source for further stem cell research with possible therapeutic
      application for spinal cord injury.

PMID- 20155460
TI  - Isolation and identification of cancer stem cells from human osteosarcom by serum
      free three-dimensional culture combined with anticancer drugs.
AB  - The cancer stem cells (CSCs) from human osteosarcoma by serum-free three
      dimensional culture combined with anticancer drugs were isolated and identified.
      The primary cells derived from human osteosarcoma were digested by trypsin to
      prepare a single-cell suspension, and mixed homogeneously into 1.2% alginate gel.
      Single-cell alginate gel was cultured with serum-free DMEM/F12 medium. Epirubicin
      (0.8 microg/mL) was added to the medium to enrich CSCs. After cultured
      conventionally for 7 to 10 days, most of cells suspended in alginate gel were
      killed by epirubicin. But few cells survived and some single-cell cloning spheres
      formed. Immunofluorescent staining for Oct3/4 and Nanog was implemented to find
      cells with properties of self-renewal and multi-potential differentiation. Cells
      from cloning spheres were transplanted into BALB/c mice to detect the
      tumorigenicity in vivo. The results showed that some cells positive for Oct3/4
      (TRITC) and Nanog (TRITC) were found in single-cell cloning spheres, and most of
      positive cells were concentrated in the core of sphere. Cells from spheres could
      form osteosarcoma in the body of mice. It was concluded that cells from single
      cell cloning spheres had the properties of the expression of parts of stem cell
      genes (Oct3/4 and Nanog), resisting anti-cancer drugs, and tumorigenicity in
      vivo. To sum up, it is believed that cells obtained from osteosarcoma by serum
      free three-dimensional culture combined with anticancer drugs are cancer stem
      cells.

PMID- 20155461
TI  - Assessing the validity of a novel model of vertebral artery type of cervical
      syndrome induced by injecting sclerosing agent next to transverse process of
      cervical vertebra.
AB  - The efficacy of injecting sclerosing agent next to transverse process of cervical
      vertebra to induce vertebral artery type of cervical syndrome (CSA) was observed.
      Twenty rabbits were randomly divided into two groups: the model group and the
      control group. The rabbits in the model group were injected with sclerosing agent
      next to transverse process of cervical vertebray, on the contrary, the rabbits in
      the control group were injected with nothing. Transcranial Doppler (TCD) was used
      to detect the average speed of blood (Vm), pulsatility index (Pi) and the
      resistant index (Ri) of the vertebral artery, hematoxylin and eosin (HE) staining
      was used to observe the morphological changes, and immunohistochemistry was used
      to detect the expression of alpha-smooth muscle actin (alpha-SMA) and matrix
      metalloproteinase-2(MMP-2). TCD showed increased Pi, Ri and decreased Vm in the
      model group (P<0.05) compared with the control group. HE staining revealed
      hyperplasia and hypertrophied smooth muscle cells in the model group (P<0.05).
      Immunohistochemistry displayed up-regulation of alpha-SMA and MMP-2 in the model
      group (P<0.05). It was concluded that injecting sclerosing agent next to
      transverse process of cervical vertebra induces remodeling of vertebral artery in
      rabbits, suggesting it is a practical method to establish CSA animal model.

PMID- 20155462
TI  - The preparation and cytocompatibility of injectable thermosensitive
      chitosan/poly(vinyl alcohol) hydrogel.
AB  - In order to investigate the strength, structure and cell cytocompatibility of
      injectable thermosensitive chitosan (CS)/poly(vinyl alcohol) (PVA) composite
      hydrogel, chitosan hydrochloride solution was transferred to a neutral pH and
      mixed with different proportions of PVA, then the gelation time and strength of
      these different hydrogels were tested and spatial structures were observed under
      a scanning electron microscopy (SEM) after freeze-drying. The cytocompatibility
      of the hydrogels was evaluated through cytotoxicity test and three-dimensional
      culture with bone marrow mesenchymal stem cells. The results showed that the
      CS/PVA solution kept in liquid state at low temperature (0-4 degrees C) and
      turned into transparent elastomer about 15-20 min at 37 degrees C. Gelation time
      was prolonged, the strength increased and porous structure became dense with the
      PVA content increased in the mixed hydrogel. The cytotoxicity grades of these
      gels were from 0 to 1. Rabbit bone marrow mesenchymal stem cells could survive
      and proliferate in the gel within 3 weeks, and the gel had good
      cytocompatibility. It was concluded that thermosensitive CS/PVA composite
      hydrogel not only has interpenetrating network structure and better mechanical
      strength, but also has good cytocompatibility, and may be used as an injectable
      scaffold for tissue engineering.

PMID- 20155463
TI  - In vitro study on human trophoblast cells infected with HCMV.
AB  - Human trophoblast cells were isolated and cultured in vitro in order to
      investigate possible pathogenesis of intrauterine infection caused by HCMV.
      Trophoblast cells were obtained by compound enzymes digestion and discontinuous
      percoll gradient. Cells and purity were identified by using immunocytochemistry
      assay with anti-CK7, Vim and beta-hCG antibodies. HCMV AD169 strain replication
      in isolated trophoblast cells and cell apoptosis were detected at different time
      points post infection (p.i.). The results showed that highly purified trophoblast
      cells were obtained. Specific virus replication was increased dramatically at the
      24th h p.i., and then increased slowly during 48 h and 72 h. Apoptosis rate of
      trophoblast cells infected with HCMV was (34.68+/-3.14)% at 24th h p.i., while
      that in control group was (15.32+/-2.34)% (P<0.05). It was suggested that highly
      purified trophoblast cells can be isolated by the simplified cell purification
      method. HCMV can infect human trophoblast cells, and be quickly replicated,
      resulting in the accelerated apoptosis of human trophoblast cells during early
      time.

PMID- 20155464
TI  - In vitro anti-hepatitis B virus effect of Hypericum perforatum L.
AB  - The anti-hepatitis B virus (HBV) effects and its mechanisms of the ethanol
      extracts of Hypericum perforatum L. (EHP) in vitro were explored. HepG2 2.2.15
      cells, a stable HBV-producing cell line, were cultured as the model system to
      observe the anti-HBV effect. The viral antigens of cellular secretion, HBsAg and
      HBeAg, were determined by enzyme linked immunosorbent assay (ELISA). The quantity
      of HBV-DNA released in the supernatant was assayed by real-time PCR. In order to
      understand the mechanisms of the suppression of HBV replication, all HBV
      promoters (Cp, Xp, S1p, S2p and Fp) with luciferase reporter gene were
      transfected into HepG2 cells respectively. Then the activities of viral promoters
      were examined by luciferase reporter assay. It was found EHP effectively
      suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose
      dependent manner, as well as the extracellular HBV DNA. And EHP could selectively
      inhibit the activity of HBV promoter Fp. Our data suggest that EHP exerts anti
      HBV effects via inhibition of HBV transcription, which helps to elucidate the
      mechanism underlying the potential therapeutic value of EHP.

PMID- 20155465
TI  - Identification of a new lamin A/C mutation in a Chinese family affected with
      atrioventricular block as the prominent phenotype.
AB  - Even though mutations in LMNA have been reported in patients with typical dilated
      cardiomyopathy (DCM) and atrioventricular block (AVB) previously, the purpose of
      this study was to disclose this novel genetic abnormality in one Chinese family
      with the atypical phenotype of progressive AVB followed by DCM with normal QRS
      interval. Genome-wide linkage analysis mapped the AVB gene in this family to a
      marker at chromosome 1q21.2, where the LMNA gene was located. Direct DNA sequence
      analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of
      LMNA, which resulted in an E82K mutation. The E82K mutation co-segregated with
      all affected individuals in the family, and was not present in 200 normal
      controls. Further clinical evaluation of mutation carriers showed that 5 of 6 AVB
      patients exhibited mild DCM with a late onset of age in the fourth and fifth
      decades. Ejection fractions were documented in 5 patients with DCM, but 4 showed
      a normal value of > or = 50%. Echocardiography showed that atrial dilatation
      occurred earlier than ventricular dilatation in the patients. This study suggests
      that progressive AVB with normal QRS interval and accompanying DCM at later
      stages may represent a distinct type of DCM. The molecular mechanism by which the
      E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of
      future studies.

PMID- 20155466
TI  - The inhibitory effects of rh-endostatin (YH-16) in combination with radiotherapy
      on lung adenocarcinoma A549 in mice and the underlying mechanisms.
AB  - In order to investigate the inhibitory effects of Endostar (rh-endostatin, YH-16)
      in combination with radiotherapy on lung adenocarcinoma A549 in mice and the
      interaction mechanisms of combined therapy, the transplantation tumor models of
      A549 lung adenocarcinoma were established. When the largest diameter of tumor
      reached 1.0 cm, all nude mice were randomly divided into 4 groups: Endostar
      group, radiotherapy group, radiotherapy plus Endostar (combined treatment) group,
      and control group (n=6 in each group). The largest diameter and the vertical
      diameter of tumor were measured at different time points. At the 16th day, mice
      were executed, and the tumors were applied to analysis of rate of tumor cell
      apoptosis, and the expression levels of basic fibroblast growth factor (bFGF)
      mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR)
      and those of vascular endothelial growth factor (VEGF) by immunohistochemistry.
      The results demonstrated that the rate of tumor inhibition in combined treatment
      group was higher than that in other groups. And the rate of tumor cell apoptosis
      in combined treatment group was also higher than that in other groups. Meanwhile,
      the levels of bFGF mRNA and VEGF expression in combined treatment group were
      lower than those in other groups. It was concluded that Endostar obviously
      enhanced the curative effectiveness of radiotherapy on lung adenocarcinoma A549
      in mice. The underlying mechanisms may involve the down-regulation of bFGF mRNA
      and VEGF expression to inhibit angiogenesis by Endostar and the cooperative
      effect of Endostar and radiotherapy to synergistically promote tumor cell
      apoptosis. And Endostar inhibits angiogenesis by down-regulating the expression
      of bFGF mRNA and VEGF.

PMID- 20155467
TI  - Therapeutic effects of all trans-retinoic acid combined with transarterial
      chemoembolization on Walker-256 hepatoma in rats.
AB  - In order to investigate the inhibitory effects of all trans-retinoic acid (ATRA)
      on differentiation and apoptosis of Walker-256 hepatocellular carcinoma cells and
      the therapeutic effects of ATRA combined with transarterial chemoembolization
      (TACE) on rat Walker-256 transplanted hepatocarcinoma, Walker-256 hepatocarcinoma
      cell lines were treated with ATRA at different concentrations. After culture for
      48 h, the inhibitory rate of cell proliferation was determined by MTT assay; the
      changes of Fas and Bcl-2 mRNA expression were determined by RT-PCR, and the
      expression levels of Caspase3 and Caspase8 proteins were detected by Western
      blot. Twenty-seven Wistar rat models of hepatocarcinoma were set up successfully
      by implanting Walker-256 cell lines. The tumor volume at the 11th day after
      implantation (V(preoperation)) was measured by magnetic resonance imaging (MRI).
      The 27 rats were randomly and equally divided into three groups, and the therapy
      scheme was performed as follows: group A (ATRA 0.1 mg+mitomycin 0.05 mL+lipiodol
      0.05 mL+gelfoam powder 0.025 mg); group B (mitomycin 0.05 mg+lipiodol 0.05
      ml+gelfoam 0.025 mg; group C (0.9% NaCl 0.2 mL). After another 11 days, MRI was
      performed once again to measure the tumor volume (V(postoperation)). The
      expression of factor and Ki VIII -67 in the tumor tissues was detected by
      immunohistochemistry. The results showed that ATRA could suppress proliferation
      of Walker-256 cell lines. After treatment of Walker-256 cell lines with ATRA, the
      expression of Fas mRNA was significantly up-regulated and the Bcl-2 mRNA was
      significantly down-regulated by ATRA at the concentration of 10 mumol/L as
      compared with the control group (P<0.05). After treatment with 10 mumol/L ATRA
      for 48 h, the Caspase3 and Caspase8 were significantly activated as compared with
      the control group (P<0.05). Significant difference existed in growth rate among
      the three groups (P<0.01) and between either two groups (P<0.05). The expression
      rate of factor VIII and Ki-67 was gradually increased from group A, group B to
      group C. The study suggests that ATRA could inhibit the proliferation of Walker
      256 cells and the effectiveness of the combined therapy (ATRA+TACE) for treating
      transplanted hepatoma of rats is superior to that of TACE alone.

PMID- 20155468
TI  - The nongenomic effects of progesterone in repressing iNOS activation through
      P38MAPK pathways in gonococci-infected polymorphonuclear leukocytes and the
      clinical significance.
AB  - Progesterone has nongenomic effects on inducible nitric oxide synthase (iNOS),
      which is mediated by mitogen activated protein kinase (MAPK) pathways. This
      effect is supposed to have some potential association with asymptomatic
      gonococcal infections in women by immunological depression. In this study,
      polymorphonuclear leukocytes (PMNs) challenged by gonococci were used to study
      the nongenomic effects of progesterone. The activation of iNOS was assessed by
      measuring [(3)H] L-arginine converses to [(3)H] L-citrulline, and the activity of
      MAPK was detected by Western blot. It was found that the activity of iNOS and the
      yields of NO were enhanced significantly in gonococci-challenged PMNs compared
      with the controls (P<0.01). Progesterone could repress the activation of iNOS
      through P38MAPK pathway within PMNs (P<0.05), which could be blocked by SB203580
      (P<0.01), but not by actinomycin D (P>0.05). It was also found subsequently that
      in the serum specimens collected from gonococci-infected but asymptomatic women,
      the progesterone level was higher than that in women with severe symptoms
      (P<0.01). Moreover, the yield of NO had an inverse correlation with progesterone.
      With these results it suggested that the rapid nongenomic effects of progesterone
      may inhibit iNOS activation and NO yields mediated by P38MAPK pathways, which
      were supposed to be concerned with asymptomatic women infected with gonococci.

PMID- 20155469
TI  - Evaluation of right ventricular global longitudinal function in patients with
      tetralogy of fallot by two-dimensional ultrasound speckle tracking imaging.
AB  - Quantification of right ventricular (RV) volume and function remains a challenge
      because of RV complex geometry by conventional echocardiography. The purpose of
      this study was to assess RV global longitudinal function in patients with
      tetralogy of Fallot (TOF) by 2-dimensional ultrasound speckle tracking imaging
      (STI). Thirty-eight patients with TOF were enrolled in this study and divided
      into child group (n=25) and adult group (n=13) according to age. Thirty-eight age
      and sex-matched normal subjects were selected as control groups including child
      control group (n=25) and adult control group (n=13). RV global longitudinal peak
      systolic strain (GLS), strain rate (GLSR(s)), early diastolic strain rate
      (GLSR(e)) and late diastolic strain rate (GLSR(a)) were measured in all subjects
      by STI from the apical 4-chamber view and compared between groups. Furthermore,
      the main factors affecting the RV global longitudinal functional parameters were
      assessed. Compared with those in controls, RV GLS, GLSR(s) and GLSR(e) were
      significantly reduced in patients with TOF (P<0.05 for all). RV GLSR(s) was
      significantly decreased in adult patients with TOF as compared with that in child
      patients (P<0.05). There was no significant difference in RV GLS, GLSR(e) and
      GLSR(a) between child and adult TOF groups (P>0.05). The diameter of right
      ventricle, main pulmonary artery and ventricular septum defect had correlations
      with RV GLSR(s) (r ( 1 )=-0.490, r ( 2 )=0.580, r ( 3 )=-0.528, respectively,
      P<0.05 for all). Tricuspid annular plane peak systolic velocity (Sm) was the
      independent predictor of RV global strain and strain rate (beta(1)=0.355, P
      (1)=0.031, beta(2)=0.307, P (2)=0.021). RV global longitudinal function is
      decreased in patients with TOF, especially in adult patients. STI is a sensitive
      and accurate technique in RV global functional assessment.

PMID- 20155470
TI  - The epidemic tendency of dental caries prevalence of school students from 1991 to
      2005 in China.
AB  - The epidemic tendency of dental caries of school students over the past 15 years
      in China was analyzed in order to provide bases for prevention of dental caries.
      Data sets of boys and girls at the age of 7, 9, 12 years (deciduous caries) and
      7, 9, 12, 14, 17 years (permanent caries) were collected from the series of
      Chinese National Surveillance on Students' Constitution and Health (CNSSCH)
      between 1991 to 2005, a survey that covers 30 provinces of and autonomous regions
      of China, with Tibet Autonomous Region and Taiwan Province excluded owing to
      unavailability of related data. According to their socioeconomic status, three
      urban regions and three rural regions (province capital must be included) were
      selected in each province, where its socioeconomic status and sports exercise can
      represent the general level of the locality. All subjects were Han students.
      Prevalence of deciduous and permanent caries was measured. In 2005, the
      prevalence of deciduous caries at 7, 9, 12 years was 52.87%, 52.04% and 9.80% in
      urban boys, 59.37%, 58.68% and 12.18% in rural boys, and that of permanent caries
      in boys at 7, 9, 12, 14, and 17 years was 2.35%, 5.63%, 13.94%, 19.05% and 21.29%
      in urban boys, 3.42%, 7.26%, 13.35%, 16.16%, 18.55% in rural boys, while in girls
      at the same age groups, the prevalence of deciduous caries was 53.53%, 49.48%,
      7.92% in urban girls, 59.95%, 56.13%, 8.85% in rural girls; the prevalence of
      permanent caries was 3.61%, 8.99%, 19.32%, 24.75%, 28.62% in urban girls, and
      3.47%, 10.65%, 17.66%, 22.52%, 24.27% in rural girls. The epidemic manifested a
      gradient distribution in age groups, which was closely related to region of the
      study population. A dramatic decreasing trend was witnessed among all sex-age
      subgroups in the rural groups between 1990 and 2005, and such a trend was
      stronger in deciduous caries than in permanent caries, however, this kind of
      decreasing trend was not steady, because there was bounce during some year.
      Although the morbidity of dental caries in China is lower than the standard set
      by the World Health Organization, and the prevalence of dental caries decreased
      from 1991 to 2005, the prospect of epidemic dental caries in China is in no way
      optimistic. The total population with dental caries is still very large and the
      prevalence decreased unstably. Therefore, financial support on school oral health
      care should be increased, and a national school oral health service network
      should be set up.

PMID- 20155471
TI  - The exact estimation of visual acuity by VEP technology: a report of 726 cases of
      eye injury.
AB  - This study explored the accuracy of using visual evoked potentials (VEP)
      technology for visual acuity estimation. The enrolled 726 patients with post
      traumatic unilateral decrease in visual acuity included the injured eyes served
      as the experimental group, and the healthy eyes as the control group. The least
      signal visual angle (LSVA), and amplitude and latency of P(100) were chosen as
      test indexes. The results under different experimental conditions were recorded
      by PRVEP technology. All data collected were processed and analyzed by SPSS
      software. The results showed that the coincidence between subjective and VEP
      visual acuity was 96.7% in control group, but there was very significant
      difference in experimental group. It was concluded that with the regression
      formulation for the amplitude of P(100) and vision under LSVA, visual acuity can
      be estimated more accurately and impartially.

PMID- 20155475
TI  - Novel D: -erythro N-octanoyl sphingosine analogs as chemo- and endocrine
      resistant breast cancer therapeutics.
AB  - PURPOSE: Resistance to endocrine and chemotherapies remains the primary cause of
      breast cancer treatment failure. We have synthesized four novel D: -erythro N
      octanoyl sphingosine analogs and catalogued their activity in drug-sensitive (MCF
      7), endocrine-resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer
      cells. METHODS: 3-(4,5-Dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay was used to determine cell viability; colony assay was performed to
      determine effects on clonogenic survival and (1)H NMR, (13)C NMR, HPLC spectra
      and elemental analytical data analyses were used to determine analog identity and
      purity. RESULTS: All four analogs inhibited both viability and clonogenic
      survival, with analog C exhibiting a log-fold improvement in anti-survival
      activity compared to the parent compound. CONCLUSION: With resistance to current
      breast cancer chemotherapies on the rise, the development of novel therapeutic
      targets is of growing importance. Our results show that lipid analogs have
      therapeutic potential in treating chemo- and endocrine-resistant breast cancer.

PMID- 20155474
TI  - Biological relevance of natural alpha-toxin fragments from Staphylococcus aureus.
AB  - Serine proteases represent an essential part of cellular homeostasis by
      generating biologically active peptides. In bacteria, proteolysis serves two
      different roles: a major housekeeping function and the destruction of foreign or
      target cell proteins, thereby promoting bacterial invasion. In the process, other
      virulence factors such as exotoxins become affected. In Staphylococcus aureus
      culture supernatant, the pore-forming alpha-toxin is cleaved by the coexpressed
      V8 protease and aureolysin. The oligomerizing and pore-forming abilities of five
      such spontaneously occurring N- and C-terminal alpha-toxin fragments were
      studied. (3)H-marked alpha-toxin fragments bound to rabbit erythrocyte membranes
      but only fragments with intact C termini, missing 8, 12 and 71 amino acids from
      their N-terminal, formed stable oligomers. All isolated fragments induced
      intoxication of mouse adrenocortical Y1 cells in vitro, though the nature of
      membrane damage for a fragment, degraded at its C terminus, remained obscure.
      Only one fragment, missing the first eight N-terminal amino acids, induced
      irreversible intoxication of Y1 cells in the same manner as the intact toxin.
      Four of the isolated fragments caused swelling, indicating altered channel
      formation. Fragments missing 12 and 71 amino acids from the N terminus occupied
      the same binding sites on Y1 cell membranes, though they inhibited membrane
      damage caused by intact toxin. In conclusion, N-terminal deletions up to 71 amino
      acids are tolerated, though the kinetics of channel formation and the channel's
      properties are altered. In contrast, digestion at the C terminus results in
      nonfunctional species.

PMID- 20155476
TI  - Blockage of angiotensin II type 2 receptor prevents thyroxine-mediated cardiac
      hypertrophy by blocking Akt activation.
AB  - Although most of effects of Angiotensin II (Ang II) related to cardiac
      remodelling can be attributed to type 1 Ang II receptor (AT(1)R), the type 2
      receptor (AT(2)R) has been shown to be involved in the development of some
      cardiac hypertrophy models. In the present study, we investigated whether the
      thyroid hormone (TH) action leading to cardiac hypertrophy is also mediated by
      increased Ang II levels or by change on AT(1)R and AT(2)R expression, which could
      contribute to this effect. In addition, we also evaluated the possible
      contribution of AT(2)R in the activation of Akt and in the development of TH
      induced cardiac hypertrophy. To address these questions, Wistar rats were treated
      with thyroxine (T(4), 0.1 mg/kg BW/day, i.p.), with or without AT(2)R blocker
      (PD123319), for 14 days. Cardiac hypertrophy was identified based on heart/body
      weight ratio and confirmed by analysis of atrial natriuretic factor mRNA
      expression. Cardiomyocyte cultures were used to exclude the influence of TH
      related hemodynamic effects. Our results demonstrate that the cardiac Ang II
      levels were significantly increased (80%, P < 0.001) as well as the AT(2)R
      expression (50%, P < 0.05) in TH-induced cardiac hypertrophy. The critical
      involvement of AT(2)R to the development of this cardiac hypertrophy in vivo was
      evidenced after administration of AT(2) blocker, which was able to prevent in 40%
      (P < 0.01) the cardiac mass gain and the Akt activation induced by TH. The role
      of AT(2)R to the TH-induced cardiomyocyte hypertrophy was also confirmed after
      using PD123319 in the in vitro studies. These findings improve understanding of
      the cardiac hypertrophy observed in hyperthyroidism and provide new insights into
      the generation of future therapeutic strategies.

PMID- 20155477
TI  - The use of the three-pronged Mayfield head clamp resulting in an intracranial
      epidural hematoma in an adult patient.
AB  - Complications from the use of a three-pronged Mayfield head clamp have been
      reported in the pediatric population, usually in children with intracranial
      pathology or hydrocephalus resulting in a thinner skull. We report the occurrence
      of an intracranial epidural hematoma in an adult patient without any prior
      intracranial pathology after the use of a Mayfield head clamp during posterior
      cervical spine surgery. The purpose of the study was to report an occurrence of
      epidural hematoma from the use of a Mayfield head clamp in an adult patient and
      to review the literature. The diagnosis of intracranial epidural hematoma should
      be considered in the presence of persistent headache and nausea after the use of
      a head clamp in spinal or intracranial surgery.

PMID- 20155478
TI  - Some physicochemical properties of the antitumor drug thiotepa and its metabolite
      tepa as obtained by density functional theory (DFT) calculations.
AB  - Density functional theory (DFT) using the B3LYP functional was applied to
      elucidate the molecular properties of the antitumor drug thiotepa and its main
      metabolite tepa. Aqueous solvent effects were introduced using the conductor-like
      polarizable continuum model (CPCM). The protocol for calculating the pK (a)
      values obtained with different cavity models was tested on a series of aziridine
      and phosphoramide compounds. An efficient computational scheme has been
      identified that uses the CPCM model of solvation with a universal force field
      (UFF) cavity. The method has been used to evaluate the basicities of thiotepa and
      its metabolite. Our calculations show that the basicities of the aziridine moiety
      of thiotepa and tepa are dramatically reduced compared to free aziridine,
      indicating that highly acidic media are needed to produce substantial yields of
      the N-protonated form of the drug. Finally, the mechanisms of reaction of the
      drug and its metabolite are discussed based on our theoretical results. The
      calculations reproduce the experimental trends very satisfactorily.

PMID- 20155479
TI  - Modelling of the provisional side-branch stenting approach for the treatment of
      atherosclerotic coronary bifurcations: effects of stent positioning.
AB  - The most common approach to treat atherosclerosis in coronary bifurcations is the
      provisional side-branch (PSB) stenting, which consists sequentially of the
      insertion of a stent in the main branch (MB) of the bifurcation and a dilatation
      of the side branch (SB) passing through the struts of the stent at the
      bifurcation. This approach can be followed by a redilatation of the MB only or by
      a Final Kissing Balloon (FKB) inflation, both strategies leading to a minor stent
      distortion in the MB. The positioning of the stent struts in the bifurcation and
      the stresses generated in the stent and vessel wall are worthy of investigation
      for a better understanding of the mechanobiology of the system. For this purpose,
      a computer model of an atherosclerotic coronary bifurcation based on the finite
      element method was developed; the effects of performing the final redilatation
      with the two strategies utilising one or two balloons and those created by a
      different stent strut positioning around the SB were investigated. Results
      correlate well with previous experimental tests regarding the deformation
      following balloon expansion. Furthermore, results confirm firstly that the re
      establishment of an optimal spatial configuration of the stent after the PSB
      approach is achieved with both strategies; secondly, results show that case of
      stent positioning with one cell placed centrally (with regard to the SB) should
      be preferred, avoiding the presence of struts inside the vessel lumen, which may
      reduce hemodynamic disturbances. The central positioning also resulted in a
      better solution in terms of lower stresses in the stent struts and, more
      importantly, in the vascular tissues.

PMID- 20155480
TI  - Angiostasis-induced vascular normalization can improve photodynamic therapy.

PMID- 20155483
TI  - Substrate specificity of ribose-5-phosphate isomerases from Clostridium difficile
      and Thermotoga maritima.
AB  - The activity of ribose-5-phosphate isomerases (RpiB) from Clostridium difficile
      for D-ribose isomerization was optimal at pH 7.5 and 40 degrees C, while that
      from Thermotoga maritima for L-talose isomerization was optimal at pH 8.0 and 70
      degrees C. C. difficile RpiB exhibited activity only with aldose substrates
      possessing hydroxyl groups oriented in the right-handed configuration (Fischer
      projections) at the C2 and C3 positions, such as D-ribose, D-allose, L-talose, L
      lyxose, D-gulose, and L-mannose. In contrast, T. maritima RpiB displayed activity
      only with aldose substrates possessing hydroxyl groups configured the same
      direction at the C2, C3, and C4 positions, such as the D- and L-forms of ribose,
      talose, and allose.

PMID- 20155481
TI  - Spontaneous arterial dissection: phenotype and molecular pathogenesis.
AB  - Arterial dissection (AD) is defined as the longitudinal splitting up of the
      arterial wall caused by intramural bleeding. It can occur as a spontaneous event
      in all large and medium sized arteries. The histological hallmark of AD is medial
      degeneration. Histological investigations, gene expression profiling and proteome
      studies of affected arteries reveal disturbances in many different biological
      processes including inflammation, proteolytic activity, cell proliferation,
      apoptosis and smooth muscle cell (SMC) contractile function. Medial degeneration
      can be caused by various rare dominant Mendelian disorders. Genetic linkage
      analysis lead to the identification of mutations in different disease-causing
      genes involved in the biosynthesis of the extracellular matrix (FBN1, COL3A1), in
      transforming growth factor (TGF) beta signaling (FBN1, TGFBR1, TGFBR2) and in the
      SMC contractile system (ACTA2, MYH11). Genome wide association studies suggest
      that the CDKN2A/CDKN2B locus plays a role in the etiology AD and other arterial
      diseases.

PMID- 20155482
TI  - tRNA nucleotidyltransferases: ancient catalysts with an unusual mechanism of
      polymerization.
AB  - RNA polymerases are important enzymes involved in the realization of the genetic
      information encoded in the genome. Thereby, DNA sequences are used as templates
      to synthesize all types of RNA. Besides these classical polymerases, there exists
      another group of RNA polymerizing enzymes that do not depend on nucleic acid
      templates. Among those, tRNA nucleotidyltransferases show remarkable and unique
      features. These enzymes add the nucleotide triplet C-C-A to the 3'-end of tRNAs
      at an astonishing fidelity and are described as "CCA-adding enzymes". During this
      incorporation of exactly three nucleotides, the enzymes have to switch from CTP
      to ATP specificity. How these tasks are fulfilled by rather simple and small
      enzymes without the help of a nucleic acid template is a fascinating research
      area. Surprising results of biochemical and structural studies allow scientists
      to understand at least some of the mechanistic principles of the unique
      polymerization mode of these highly unusual enzymes.

PMID- 20155484
TI  - pHsh vectors, a novel expression system of Escherichia coli for the large-scale
      production of recombinant enzymes.
AB  - Gene expression system Hsh is developed to increase enzyme production and to
      decrease the cost in the induction of gene expression in Escherichia coli. The
      vectors of Hsh system were constructed by combining a synthesized heat-shock
      promoter with a synthesized terminator and an origin of replication derived from
      pUC19 in which the expression of foreign genes was regulated by an alternative
      sigma factor, sigma(32) of E. coli. In comparison, the Hsh promoter gave a 2.4
      fold higher production for xynIII gene encoding a xylanase than existing heat
      shock inducible promoter p (L), 1.2-fold and 3-fold production for xar gene
      encoding a arabinosidase than trc and T(7) promoter, respectively. The flow-in
      heat technique created a rapid rise in temperature for effective induction of
      gene expression in bioreactor scale.

PMID- 20155485
TI  - Fermentation of corn fiber hydrolysate to lactic acid by the moderate thermophile
      Bacillus coagulans.
AB  - A strain of Bacillus coagulans that converted mixed sugars of glucose, xylose,
      and arabinose to L: -lactic acid with 85% yield at 50 degrees C was isolated from
      composted dairy manure. The strain was tolerant to aldehyde growth inhibitors at
      2.5 g furfural/l, 2.5 g 5-hydroxymethylfurfural/l, 2.5 g vanillin/l, and 1.2 g p
      hydroxybenzaldehyde/l. In a simultaneous saccharification and fermentation
      process, the strain converted a dilute-acid hydrolysate of 100 g corn fiber/l to
      39 g lactic acid/l in 72 h at 50 degrees C. Because of its inhibitor tolerance
      and ability to fully utilize pentose sugars, this strain has potential to be
      developed as a biocatalyst for the conversion of agricultural residues into
      valuable chemicals.

PMID- 20155486
TI  - Immobilization of glucose oxidase on Fe3O4/SiO2 magnetic nanoparticles.
AB  - Glucose oxidase (GOD) was covalently immobilized onto Fe(3)O(4)/SiO(2) magnetic
      nanoparticles (FSMNs) using glutaraldehyde (GA). Optimal immobilization was at pH
      6 with 3-aminopropyltriethoxysilane at 2% (v/v), GA at 3% (v/v) and 0.143 g GOD
      per g carrier. The activity of immobilized GOD was 4,570 U/g at pH 7 and 50
      degrees C. The immobilized GOD retained 80% of its initial activity after 6 h at
      45 degrees C while free enzyme retained only 20% activity. The immobilized GOD
      maintained 60% of its initial activity after 6 cycles of repeated use and
      retained 75% of its initial activity after 1 month at 4 degrees C whereas free
      enzymes retained 62% of its activity.

PMID- 20155487
TI  - Sphingolipids of human umbilical cord vein and their alteration in preeclampsia.
AB  - Preeclampsia is the most common pregnancy-associated pathological syndrome. It is
      accompanied by the accumulation of free fatty acids, acylglycerols and
      cholesterol esters in the umbilical cord vein (UCV). We evaluate the sphingolipid
      composition of UCV and its alteration in preeclampsia. The veins were taken from
      10 newborns delivered by healthy mothers and 10 newborns delivered by mothers
      with preeclampsia. Thin layer chromatography, solid-phase extraction and high
      performance liquid chromatography were employed for sphingolipid analyses. The
      UCV walls of newborns delivered by healthy mothers are abundant in sphingomyelins
      and ceramides, whereas the amounts of sphingoid bases are rather low.
      Preeclampsia is associated with a significant decrease in sphingomyelins and
      ceramides, whereas the sphingoid bases changed in uncharacteristic manner. The
      increase in sphinganine and sphingosine 1-phosphate was accompanied with a
      decrease in sphingosine, hydroxysphinganine and sphinganine 1-phosphate. Stearate
      is the dominating fatty acid in sphingomyelins and ceramides of both control and
      preeclamptic veins. Sphingolipids and some sphingoid bases are bioactive
      molecules which contribute to regulation of signal transduction pathways, protein
      sorting and mediation of cell-to-cell interactions and recognition. The
      alteration in sphingolipid content may modify the metabolism of UCV wall
      resulting in remodelling of its composition.

PMID- 20155488
TI  - Proximity of Na+ -Ca2+ -exchanger and sarco/endoplasmic reticulum Ca2+ pump in
      pig coronary artery smooth muscle: fluorescence microscopy.
AB  - Pig coronary artery smooth muscle expresses the Na(+)-Ca(2+)-exchanger NCX1 and
      the sarco/endoplasmic reticulum (SER) Ca(2+) pump SERCA2. NCX has been proposed
      to play a role in refilling the SER Ca(2+) pool. Caveolae may also direct Ca(2+)
      traffic during cell signaling. Here, we use immunofluorescence microscopy to
      determine if there is proximity between NCX1, SERCA2, and the caveolar protein
      caveolin-1. Stacks of images of cell surface domains were analyzed. Image stacks
      for one protein were analyzed for overlap with another protein, with and without
      randomization or image shifting. Within the resolution of light microscopy, there
      is significant overlap in the distributions of NCX1, SERCA2, and caveolin-1 but
      the three proteins are not always co-localized. The proximity between NCX1,
      SERCA2 is consistent with the assertion that NCX may supply Ca(2+) for refilling
      the SER but this relationship is only partial. Similarly, caveolae may direct
      traffic in some Ca(2+) signaling pathways but not others.

PMID- 20155489
TI  - Common genetic variation of insulin-like growth factor-binding protein 1 (IGFBP
      1), IGFBP-3, and acid labile subunit in relation to serum IGF-I levels and
      mammographic density.
AB  - Mammographic density is strongly related to increased breast cancer risk.
      Accumulating evidence indicates that a role for the IGF-pathway in mammographic
      density and breast cancer development. Here, we investigate whether common
      genetic variation in this pathway influences insulin-like growth factor-I (IGF-I)
      levels and mammographic density. In 1,916 premenopausal women within the Prospect
      EPIC cohort, we examined associations of 14 haplotype tagging SNPs in the ALS,
      IGFBP1, and IGFBP3 genes with IGF-I circulating levels and mammographic density.
      In 657 women, who became postmenopausal during follow-up, we investigated how
      these SNPs were related with the decrease in density over menopause. Linear
      regression models were used for statistical analysis. None of the ALS or IGFBP3
      SNPs were statistically significantly associated with IGF-I levels or
      mammographic density. The CC genotype for rs1908751 (IGFBP1) was associated with
      lower levels of IGF-I (110.9 ng/ml) compared to the CT/TT genotypes (115.7 ng/ml)
      (P = 0.04). Women with the CC genotype also had lower percent density, although
      not statistically significantly (P = 0.12). Women carrying the AA genotype for
      rs1995051 (IGFBP1) showed that borderline significantly lower IGF-I levels (P =
      0.06) and significantly lower mammographic density (40.3% compared to 43.5% in
      the GG/GA genotypes; P = 0.05). No relationships were found for any of the SNPs
      in relation with changes in breast density over menopause. These findings suggest
      that common genetic variation in the IGFBP1 gene is weakly related to IGF-I
      levels and mammographic density. Our results do not provide support for such a
      role of genetic variants in the IGFBP3 and ALS genes.

PMID- 20155490
TI  - CD4+ T cell epitope discovery and rational vaccine design.
AB  - T cell epitope-driven vaccine design employs bioinformatic algorithms to identify
      potential targets of vaccines against infectious diseases or cancer. Potential
      epitopes can be identified with major histocompatibility complex (MHC)-binding
      algorithms, and the ability to bind to MHC class I or class II indicates a
      predominantly CD4(+) or CD8(+) T cell response. Furthermore, an epitope-based
      vaccine can circumvent evolutionary events favoring immune escape present in
      native proteins from pathogens. It can also focus on only the most relevant
      epitopes (i.e. conserved and promiscuous) recognized by the majority of the
      target population. Mounting evidence points to the critical role of CD4(+) T
      cells in natural antigen encounter and active immunization. In this paper the
      need for CD4(+) T cell help in vaccine development, the selection of CD4(+) T
      cell epitopes for an epitope-based vaccine, and how the approach can be used to
      induce a protective effect are reviewed.

PMID- 20155491
TI  - A highly sensitive caffeine immunoassay based on a monoclonal antibody.
AB  - A new immunoassay has been developed based on a commercially available anti
      caffeine monoclonal antibody and a de novo synthesized tracer, using horseradish
      peroxidase and UV-visible detection. Caffeine, which is frequently found in
      surface waters, can be quantified with a relative error lower than 20% for
      concentrations above 0.025 microg L(-1) (limit of quantitation, direct analysis).
      The limit of detection is 0.001 microg L(-1) and can be reduced by solid-phase
      extraction (SPE). Moreover, with minor adaptations, the assay can be used to
      quantify caffeine in several beverages, shampoo, and caffeine tablets. The
      results obtained by ELISA correlate well with those from liquid chromatography
      tandem mass spectrometry (LC-MS-MS) for the tested matrices. Several surface
      waters from Berlin were analysed and all tested positive for caffeine, with
      concentrations higher than 0.030 microg L(-1). In one run 66 samples can be
      analysed within 2 h.

PMID- 20155492
TI  - RNA aptamer-based optical nanostructured sensor for highly sensitive and label
      free detection of antigen-antibody reactions.
AB  - Developments of optical protein sensors with nanostructure based on the noble
      metals have currently received great attention for their high efficiency and
      simultaneous analysis of various important biomolecules from proteomics to
      genetics. In this study, we exploited the absorbance spectra of gold-capped
      nanoparticles substrate for label-free detections of antigen-antibody reactions
      using a specific thiolated RNA aptamer. These synthesized RNA aptamers have been
      optimized to bind to the Fc portion of the human IgG1 subclass, due to their
      ability to orient antibodies direction on the gold surface. After attaching the
      anti-fibrinogen antibodies on the surface via these linkers, our thiolated RNA
      aptamer-based nanostructured sensors were easily applicable to specific
      detections of fibrinogen with a limit of detection of 0.1 ng/mL. These
      nanostructured sensor-based models will open a way to display numerous
      immunosensors as well as to develop other functionally similar sensors which
      could then be expanded into multi-arrays assay systems.

PMID- 20155493
TI  - Generic sample preparation combined with high-resolution liquid chromatography
      time-of-flight mass spectrometry for unification of urine screening in doping
      control laboratories.
AB  - A unification of doping-control screening procedures of prohibited small molecule
      substances--including stimulants, narcotics, steroids, beta2-agonists and
      diuretics--is highly urgent in order to free resources for new classes such as
      banned proteins. Conceptually this may be achieved by the use of a combination of
      one gas chromatography-time-of-flight mass spectrometry method and one liquid
      chromatography-time-of-flight mass spectrometry method. In this work a
      quantitative screening method using high-resolution liquid chromatography in
      combination with accurate-mass time-of-flight mass spectrometry was developed and
      validated for determination of glucocorticosteroids, beta2-agonists, thiazide
      diuretics, and narcotics and stimulants in urine. To enable the simultaneous
      isolation of all the compounds of interest and the necessary purification of the
      resulting extracts, a generic extraction and hydrolysis procedure was combined
      with a solid-phase extraction modified for these groups of compounds. All 56
      compounds are determined using positive electrospray ionisation with the
      exception of the thiazide diuretics for which the best sensitivity was obtained
      by using negative electrospray ionisation. The results show that, with the
      exception of clenhexyl, procaterol, and reproterol, all compounds can be detected
      below the respective minimum required performance level and the results for
      linearity, repeatability, within-lab reproducibility, and accuracy show that the
      method can be used for quantitative screening. If qualitative screening is
      sufficient the instrumental analysis may be limited to positive ionisation,
      because all analytes including the thiazides can be detected at the respective
      minimum required levels in the positive mode. The results show that the
      application of accurate-mass time-of-flight mass spectrometry in combination with
      generic extraction and purification procedures is suitable for unification and
      expansion of the window of screening methods of doping laboratories. Moreover,
      the full-scan accurate-mass data sets obtained still allow retrospective
      examination for emerging doping agents, without re-analyzing the samples.

PMID- 20155494
TI  - Latissimus dorsi transfer for treatment of irreparable rotator cuff tears.
AB  - Massive rotator cuff tendon ruptures are not uncommon in older patients. We
      propose the transfer of the latissimus dorsi muscle for treatment of irreparable
      ruptures associated with functional impairment and chronic pain. Five women and
      11 men were so treated and reviewed with an average follow-up of 26 months. The
      mean age was 60 years. Four patients also had subscapularis deficiency. Results
      were assessed with the Constant score and the Oxford shoulder score. Humeral head
      position was analysed. Statistical analysis was performed by the Wilcoxon non
      parametrical test. The Constant score increased by 24.2% (p = 0.001) with all
      parameters showing improvement. Nine patients showed improved humeral head
      positioning in internal rotation. Three of four patients with a deficient
      subscapularis had unfavourable results. Latissimus dorsi transfer for the
      treatment of irreparable massive rotator cuff tears leads to a substantial
      clinical improvement. An intact subscapularis tendon is mandatory.

PMID- 20155495
TI  - Surgical management of severe scoliosis with high risk pulmonary dysfunction in
      Duchenne muscular dystrophy: patient function, quality of life and satisfaction.
AB  - In a previous study, the authors reported the clinical and radiological results
      of Duchenne muscular dystrophy (DMD) scoliosis surgery in 14 patients with a low
      FVC of <30%. The purpose of this study was to determine if surgery improved
      function and QOL in these patients. Furthermore, the authors assessed the
      patients' and parents' satisfaction. %FVC increased in all patients after
      preoperative inspiratory muscle training. Scoliosis surgery in this group of
      patients presented no increased risk of major complications. All-screw
      constructions and fusion offered the ability to correct spinal deformity in the
      coronal and pelvic obliquity initially, intermediate and long-term. All patients
      were encouraged to continue inspiratory muscle training after surgery. The mean
      rate of %FVC decline after surgery was 3.6% per year. Most patients and parents
      believed scoliosis surgery improved their function, sitting balance and quality
      of life even though patients were at high risk for major complications. Their
      satisfaction was also high.

PMID- 20155496
TI  - Minimally invasive video-assisted thyroidectomy (MIVAT): what is the real
      advantage?
AB  - BACKGROUND: The evolution of video-assisted or laparoscopic surgical techniques
      in the last several years has changed the surgical treatment approach to many
      diseases, also in endocrine surgery. MATERIALS AND METHODS: From July 2005 to
      March 2009, we treated 211 patients with minimally invasive video-assisted
      thyroidectomy (MIVAT). The procedure was performed in accordance with Miccoli's
      technique using an Ultracision CS 14 (Ethicon Endosurgery) and/or Single Use
      Automatic Clip Applier S-90 (Autosuture). In all cases, we recorded the incidence
      of postoperative hypocalcaemia as a serum calcium value lower than 8 mg/dl with
      or without hypocalcaemic symptoms, postoperative haemorrhage or nerve palsy, mean
      operative time. All patients were also assessed for postoperative pain and given
      a visual analogue score from 0 to 10 at 1 and 24 h after surgery. We matched
      these results with a group of 587 patients treated during the same period with
      traditional thyroidectomy. RESULTS: The female/male ratio was 4:1; the mean age
      of the patients was 50.6 years. In the MIVAT group, the mean time of surgical
      procedure decreased by 52.4 min. We observed 16 hypocalcaemic cases with clinical
      symptoms (7.58%) (six of these cases were published in a previous article and
      were among the first 100 cases treated) and 59 cases of serologic hypocalcaemia
      (27.9%) (serum calcium lower than 8 mg/dl); the mean value of calcium
      concentration was 7.5 +/- 0.27 mg/dl. We observed six cases of monolateral nerve
      palsy, and after 6 months, a definitive palsy in two cases (0.9%); these two
      cases were in the first 25 cases treated. Comparisons with traditional
      thyroidectomy group showed statistically significant differences in postoperative
      serologic hypocalcaemia (p < 0.001), no difference in mean calcium value (p =
      0.41) and no statistical difference in the incidences of nerve palsy and
      haemorrhage. CONCLUSIONS: Patients treated with MIVAT showed an improvement in
      incidence of postoperative hypocalcaemia, postoperative pain, postoperative stay,
      psychophysical recovery and cosmetic result.

PMID- 20155497
TI  - Theoretical study of hydrogen bonding interactions on MDI-based polyurethane.
AB  - Hydrogen bonding among hard-hard segments and hard-soft segments in 4,4'
      diphenylmethane diisocyanate (MDI)-based polyurethane was investigated
      theoretically by density functional theory (DFT). Both B3LYP/6-31G* and B3PW91/6
      31G* methods gave good structures, reasonable Mulliken charges, binding energies,
      dipole moments, and good infrared (IR) spectra trends in predicting hydrogen
      bonding. Bond distances R(N-H...O), which were in the range of 3.005-3.028 A for
      the carbonyl bonded hydrogen-bond, and 3.074-3.075 A for the ester bonded
      hydrogen-bond, are in reasonable agreement with experimental values. Most of the
      carbonyl oxygen in polyurethane exists in a hydrogen-bonded form. Complex (c),
      with two carbonyl hydrogen bonds, features the largest dipole moment, while
      complex (d) with two ester hydrogen bonds, possesses the smallest dipole moment,
      i.e., lower than that of the isolated monomer, which may be due to the symmetry
      of the two monomers. These results confirm that the DFT method is a good tool
      with which to study weak interactions, and indicate that hydrogen bonds are
      indeed formed between carbonyl and N-H, or ester and N-H, with the former being
      stronger.

PMID- 20155499
TI  - Elucidation of a diurnal pattern of catechin exudation by Centaurea stoebe.
AB  - The exudation of secondary metabolites at phytotoxic concentrations has been
      proposed as a mechanism of invasion for some exotic plant species. Catechin is a
      natural flavanoid implicated in the potential allelopathic interactions of
      Centaurea stoebe. However, recent studies have shown that catechin is highly
      unstable and not likely to accumulate in growing medium at phytotoxic
      concentrations. All previous studies that investigated the allelopathic potential
      of catechin assumed a continuous exudation of this compound by C. stoebe.
      Contrary to this, but similar to many other plant secondary metabolites, we
      hypothesized that catechin exudation may exhibit a pulsed pattern that could
      facilitate its transient accumulation. Further, we aimed at optimizing a more
      sensitive detection technique. We tested the hypothesis by quantifying the
      diurnal pattern of catechin release by C. stoebe in a hydroponic system. Using
      sample processing, based on a solid phase extraction technique, and more
      sensitive fluorescent detection parameters, we were able to quantify catechin in
      the picomolar range from the growing medium. Catechin exudation exhibited a
      possible diurnal rhythm with respect to light intensity, with the highest
      concentration at 6 h after exposure to sunlight. Catechin also was found to
      undergo a degradation reaction resulting in a transient abundance of pyrocatechol
      in our system.

PMID- 20155500
TI  - Kairomonal response of the parasitoid, Bracon hebetor Say, to the male-produced
      sex pheromone of its host, the greater Waxmoth, Galleria mellonella (L.).
AB  - Bracon hebetor is a larval ectoparasitoid that utilizes several pests belonging
      to the family Pyralidae (Lepidoptera) as hosts. In the present study, we analyzed
      the kairomonal response of this wasp to the male-produced sex pheromone of a
      host, the greater wax moth Galleria mellonella, an economically important pest of
      honeybees, Apis mellifera. Coupled gas chromatography-electroantennographic
      detection (GC-EAD) revealed three compounds in headspace collections from male G.
      mellonella that elicited responses from B. hebetor antennae: decanal and the
      previously identified sex pheromone components, nonanal and undecanal. Y-tube
      olfactometer tests that used naive, mated wasps showed that females, but not
      males, were highly attracted to (a) male G. mellonella headspace samples, (b) two
      synthetic blends of nonanal and undecanal (in ratios matching that found in male
      moth samples), and (c) the two aldehydes tested individually. Further, female
      wasps did not discriminate between a blend of aldehydes and male G. mellonella
      headspace. In dose-response trials that used octanal, nonanal, decanal, and
      undecanal, no difference in EAG responses of the two sexes was observed, except
      for undecanal at the second highest dose, for which female antennae showed
      significantly larger responses than did male antennae. When the two binary blends
      were tested at different doses, female wasps were significantly attracted to the
      two highest doses (1 microg and 10 microg), but not to the lowest dose (100 ng).
      Our results show that females of this economically important parasitoid utilize
      the male-produced sex pheromone of a host as an indirect cue to guide them to
      potential oviposition sites.

PMID- 20155504
TI  - Three-dimensional observation of the mouse embryo by micro-computed tomography:
      composition of the trigeminal ganglion.
AB  - The purpose of this study was to demonstrate a micro-computed tomography (CT)
      method for observations of the mouse embryo. At 13.0 days post-coitum, mouse
      embryos were fixed in 4% paraformaldehyde for 24 h and stained en bloc by osmium
      tetroxide overnight. The embryos were then embedded in paraffin using standard
      methods for 24 h. Specimens were analyzed by micro-CT and image processing was
      performed. Organs containing nervous and blood systems could be viewed as a
      result of different osmium-staining densities. The trigeminal ganglion was imaged
      using three-dimensional techniques. Observation of the embryo was possible by
      micro-CT with osmium tetroxide staining.

PMID- 20155502
TI  - Can interaction of materials with the dentin-pulp complex contribute to dentin
      regeneration?
AB  - Understanding outcomes of the interaction between a dental material and tooth
      tissue is important in terms not only of biocompatibility but also of the
      potential for the material to modulate the response of the tissue. This
      interaction is influenced by many factors, including the chemistry of the
      material and any of its eluted components or degradation products, and the manner
      in which the tissue responds to these agents. Past studies of this interaction
      have primarily been aimed at identifying cytotoxic effects. More recently,
      investigations have focused on specific cellular responses, and in particular, on
      understanding how the materials themselves actually may contribute to
      regenerative processes in the tooth. Recent work has demonstrated the
      solubilization of proteins from dentin exposed to certain materials, such as
      calcium hydroxide, mineral trioxide aggregate, and acidic solutions that relate
      to those used in dentin bonding agents, with the subsequent modulation by these
      proteins of gene expression in odontoblast-like cells. This work suggests that
      dentin bridge formation under such materials may be stimulated through this
      process. Thus, there is much merit in examining both how new dental materials can
      be developed and how more traditional ones can be modified to preferentially
      stimulate regenerative processes when preferred. This review summarizes current
      knowledge about the potential beneficial effects derived from the interaction of
      dental materials with the dentin-pulp complex, as well as potential future
      developments in this exciting field.

PMID- 20155505
TI  - Effect of particle diameter on air polishing of dentin surfaces.
AB  - We examined the abrasiveness of glycine powders with particle diameters of 63 and
      100 mum by measuring the depth and volume of defects produced during air
      polishing of human dentin. A total of 36 extracted human teeth were embedded in
      acrylic resin. The resin blocks were polished until the dentin surfaces were
      exposed. The nozzle of an air polisher was mounted 4 mm from the dentin surface,
      and the dentin surface was treated for 5 s at one of two angles of incidence (45
      degrees or 90 degrees). Three materials were used in the polishing process:
      NaHCO(3) powder with a mean particle diameter of 100 microm (Handy Jet Powder),
      glycine powder with a mean particle diameter of 63 microm (Handy Jet Powder
      PMTC), and glycine powder with a mean particle diameter of 100 microm (Handy Jet
      Powder Recall). The defect depth at both angles was significantly deeper after
      treatment with Handy Jet Powder or Handy Jet Powder PMTC. The defect volume was
      the greatest with Handy Jet Powder, followed by Handy Jet Powder PMTC, and Handy
      Jet Powder Recall. The larger diameter glycine powder resulted in less damage to
      the dentin.

PMID- 20155503
TI  - Antifungal drug resistance of oral fungi.
AB  - Fungi comprise a minor component of the oral microbiota but give rise to oral
      disease in a significant proportion of the population. The most common form of
      oral fungal disease is oral candidiasis, which has a number of presentations. The
      mainstay for the treatment of oral candidiasis is the use of polyenes, such as
      nystatin and amphotericin B, and azoles including miconazole, fluconazole, and
      itraconazole. Resistance of fungi to polyenes is rare, but some Candida species,
      such as Candida glabrata and C. krusei, are innately less susceptible to azoles,
      and C. albicans can acquire azole resistance. The main mechanism of high-level
      fungal azole resistance, measured in vitro, is energy-dependent drug efflux. Most
      fungi in the oral cavity, however, are present in multispecies biofilms that
      typically demonstrate an antifungal resistance phenotype. This resistance is the
      result of multiple factors including the expression of efflux pumps in the fungal
      cell membrane, biofilm matrix permeability, and a stress response in the fungal
      cell. Removal of dental biofilms, or treatments to prevent biofilm development in
      combination with antifungal drugs, may enable better treatment and prevention of
      oral fungal disease.

PMID- 20155506
TI  - Bond strength of adhesives to dentin contaminated with smoker's saliva.
AB  - The purpose of this study was to determine the effects of contamination with
      smoker's and non-smoker's saliva on the bond strength of resin composite to
      superficial dentin using different adhesive systems. The interfacial structure
      between the resin and dentin was evaluated for each treatment using environmental
      scanning electron microscopy (ESEM). Freshly extracted human molars were ground
      with 600-grit SiC paper to expose the superficial dentin. Adhesives [One-Up-Bond
      F-Plus (OUFP) and Adper-Prompt-L-Pop (APLP)] and resin composite (TPHSpectrum)
      were bonded to the dentin (n = 8/group, 180 total specimens) under five surface
      conditions: control (adhesive applied following manufacturers' instructions);
      saliva, then 5-s air dry, then adhesive; adhesive, saliva, 5-s air dry; adhesive,
      saliva, 5-s water rinse, 5-s air dry (ASW group); and adhesive, saliva, 5-s water
      rinse, 5-s air dry, reapply adhesive (ASWA group). After storage in water at 37
      degrees C for 24 h, the specimens were debonded under tension at a speed of 0.5
      mm/min. ESEM photomicrographs of the dentin/adhesive interfaces were taken. Mean
      bond strength ranged from 8.1 to 24.1 MPa. Fisher's protected least significant
      difference (P = 0.05) intervals for critical adhesive, saliva, and surface
      condition differences were 1.3, 1.3, and 2.1 MPa, respectively. There were no
      significant differences in bond strength to dentin between contamination by
      smoker's and nonsmoker's saliva, but bond strengths were significantly different
      between adhesive systems, with OUFP twice as strong as APLP under almost all
      conditions. After adhesive application and contamination with either smoker's or
      nonsmoker's saliva followed by washing and reapplication of the adhesive (ASWA
      group), the bond strength of both adhesive systems was the same as that of the
      control group.

PMID- 20155507
TI  - The relationship between physiologic halitosis and periodontopathic bacteria of
      the tongue and gingival sulcus.
AB  - To determine the influence of oral status on halitosis, the relationship between
      halitosis and periodontopathic bacteria present in plaque on the tongue and the
      subgingival sulcus was examined in 62 periodontally healthy adults. Halitosis
      indicators used were the organoleptic score; gas chromatography results [total
      volatile sulfur compounds (VSCs) = H(2)S + CH(3)SH + (CH(3))(2)S]; Halimeter
      values; and the results of three clinical tests, plaque control record (PlCR),
      plaque index (PlI), and tongue coat status. Significant correlations with
      organoleptic scores was observed for PlCR, PlI, tongue coat status, VSC amounts,
      and Halimeter values, indicating that halitosis in periodontally healthy subjects
      tended to originate from tongue plaque deposits. Polymerase chain reaction
      analysis was used to detect six periodontopathic bacteria (Aggregatibacter
      actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis,
      Prevotella intermedia, Tannerella forsythensis, and Treponema denticola) from the
      tongue and subgingival plaque. Significant effects on the organoleptic scores,
      tongue coat status, total VSC, H(2)S and CH(3)SH amounts, and Halimeter values
      were observed only for T. denticola and F. nucleatum and only in the tongue
      plaque, not in the subgingival plaque. Thus, therapies developed to inhibit the
      growth of these bacteria may lead to future treatments of halitosis.

PMID- 20155508
TI  - Experimental study of antiangiogenic gene therapy targeting VEGF in oral cancer.
AB  - It is well known that tumor angiogenesis plays an important role in local growth
      and metastasis of oral cancer; therefore, inhibiting angiogenesis is considered
      to be effective for treating oral cancer. This study aimed to investigate the
      effectiveness of systemically available antiangiogenic gene therapy targeting
      vascular endothelial growth factor (VEGF), which is one of the most important
      angiogenesis accelerators. We administered a soluble form of VEGF receptor
      expressing gene incorporated into adenovirus (AdVEGF-ExR) intraperitoneally to
      nude mice to which oral cancer cell lines (SAS, HSC-3, and Ca9-22) had been
      transplanted subcutaneously in vivo to inhibit angiogenesis and tumor
      proliferation. Then, we measured tumor volumes over time, and tumors were
      enucleated and examined histopathologically and immunohistologically at 28 days
      after AdVEGF-ExR administration. Compared to the controls to which we
      administered AdLacZ or saline, significant antiproliferative effects were
      observed (P < 0.05) in the AdVEGF-ExR administration group, and extensive tumor
      necrosis was found histopathologically. Immunohistochemical analysis with CD34
      (NU-4A1) revealed tumor angiogenesis was suppressed significantly (P < 0.05), and
      that with ssDNA revealed apoptosis induction was significantly high (P < 0.05) in
      the AdVEGF-ExR group. However, analysis with Ki-67 (MIB-1) revealed tumor
      proliferative capacity was not significantly different between the groups.
      Consequently, we consider that AdVEGF-ExR administration achieved tumor growth
      suppression by inhibiting angiogenesis and inducing apoptosis, but not by
      inhibiting the proliferative capacity of tumor cells. Neither topical
      administration of a soluble form of VEGF receptor (sVEGFR) to the tumor nor a
      megadose was needed to achieve this inhibition effect. These results suggest gene
      therapy via sVEGFR would be an effective oral cancer therapy and benefit future
      clinical applications.

PMID- 20155509
TI  - Pain is associated with an endophytic cancer growth pattern in patients with oral
      squamous cell carcinoma before treatment.
AB  - The origins and mechanisms of pain arising from oral cancer are important. Oral
      cancer pain impairs a patient's quality of life. This study was undertaken to
      elucidate significant risk factors associated with spontaneous pain in patients
      with untreated oral squamous cell carcinoma (OSCC) before treatment. A total of
      113 patients (82 men, 31 women; median age, 64 years) with untreated OSCC were
      examined. Correlations between spontaneous pain in the primary site and sex, age,
      primary site, TN stage, clinical stage, and clinical growth type of cancer
      (exophytic or endophytic), as well as the degree of histological differentiation
      and the histological mode of invasion were evaluated. At the initial examination,
      42 (37%) of patients had spontaneous pain. In univariate statistical analyses,
      reported pain correlated significantly with patient age and the clinical growth
      type of the cancer, as well as with the degree of histological differentiation
      and the histological mode of invasion. Multiple logistic regression analysis
      showed significant correlations between reported spontaneous pain and the
      clinical growth type of the cancer (P = 0.0003; odds ratio, 9.5; 95% confidence
      interval, 2.8-32.3), as well as reported spontaneous pain and the histological
      mode of invasion (P = 0.0026; odds ratio, 4.7; 95% confidence interval, 1.7
      12.7). Clinical and histological endophytic growth patterns of OSCC might be
      significant risk factors for the presence of spontaneous pain before treatment.

PMID- 20155510
TI  - Cephalometric evaluation of maxillary sinus sizes in different malocclusion
      classes.
AB  - We found few studies on the association between maxillary sinus size and
      malocclusion in an electronic search using PubMed. The purpose of this study was
      to investigate maxillary sinus size in different malocclusion groups and the
      association between maxillary sinus size and dentofacial morphology by the use of
      lateral cephalometric radiographs. A total of 120 lateral cephalograms were used.
      These radiographs were derived from subjects with skeletal Class I, Class II, and
      Class III malocclusions, classified on the basis of the A-N-B angle. Each
      malocclusion group consisted of 20 boys and 20 girls ranging in age from 12 to 16
      years. Two linear measurements and three area measurements were made to evaluate
      maxillary sinus size, and four angular and eight linear measurements were made to
      evaluate dentofacial morphology. Analysis of variance and Pearson's correlation
      analysis were performed for statistical comparison. The maxillary sinuses showed
      no significant differences in size between the different classes of skeletal
      malocclusion or between sexes. However, the maxillary sinus measurements were
      significantly correlated with several dentofacial morphological measurements.
      When formulating an orthodontic treatment plan, orthodontists should take into
      consideration the fact that the patients 12 to 16 years old with large cranial
      bases and nasomaxillary complexes tend to have larger maxillary sinuses, but
      there is no significant association between maxillary sinus size and the A-N-B
      angle denoting the sagittal skeletal jaw relationship.

PMID- 20155511
TI  - Quantification of disc displacement in internal derangement of the
      temporomandibular joint using magnetic resonance imaging.
AB  - Many measures have been developed to determine the extent of disc displacement in
      internal derangements of the temporomandibular joint (TMJ) using magnetic
      resonance imaging. The purpose of this study was to develop a quantitative method
      of analyzing disc position and to evaluate the positions of the disc in internal
      derangements of the TMJ (group 1, with reduction; group 2, without reduction).
      Magnetic resonance images of 150 TMJs in 20 healthy volunteers and 55 patients
      with internal derangements were evaluated. The anatomical points of interest of
      the TMJ, including the anterior (DA) and posterior (DP) points of the disc, were
      marked on parasagittal magnetic resonance images of the TMJ disc taken in both
      the closed- and the open-mouth positions. All points were recorded using an x-y
      coordinate system, with reference to a referral line. In the closed-mouth
      position, the DP in patients in group 1 was situated in a more-anterior direction
      than the DP in volunteers. The DP in group 2 was located further anterior and
      inferior than the DP in group 1. However, the position of the DA did not differ
      between group 1 and group 2. In the open-mouth position, the DP was displaced
      anteroinferiorly to a greater extent in group 2 than in group 1 (one-way ANOVA,
      followed by Scheffe's test; P < 0.0001). The distance between the disc points in
      the closed- and open-mouth positions was also evaluated. Comparison of the disc
      point position in the closed- and open-mouth positions in symptomatic and
      asymptomatic displaced TMJ discs revealed no significant difference. In
      conclusion, most of our results quantitatively support previously reported
      findings in imaging, surgical, and histopathological studies of TMJ internal
      derangement. We suggest that our measure of disc position of the TMJ would be
      useful to assess the status and response to treatment of internal derangements of
      the TMJ.

PMID- 20155512
TI  - Ice cube stimulation helps to improve dysgeusia.
AB  - Dysgeusia causes a decrease in appetite, and it is one of the major factors in
      undernutrition. Dysgeusia is elicited by numerous causes, and in many cases it is
      still difficult to treat the various symptoms complained of by patients. We
      herein report a case in which dysgeusia was improved by transient cooling of the
      mouth.

PMID- 20155513
TI  - Clinical application of a custom-made bioresorbable raw particulate
      hydroxyapatite/poly-L-lactide mesh tray for mandibular reconstruction.
AB  - Mandibular reconstruction using particulate cancellous bone and marrow (PCBM)
      allows functional oral reconstruction. Although ready-made titanium trays are the
      most common material used in this method, they have some disadvantages such as
      difficulty in making them form a suitable contour for the defect, and the need
      for removal. A forged composite of raw particulate hydroxyapatite (HA)/poly-L
      lactide (PLLA) is a bioresorbable material that is stronger than pure PLLA and
      induces bone formation more rapidly. We present two cases successfully treated
      with custom-made bioresorbable HA/PLLA mesh trays for mandibular reconstruction.
      A 29-year-old woman with recurrent ameloblastoma and a 66-year-old man with a
      recurrent keratinized odontogenic tumor of the mandible gave informed consent for
      this reconstruction technique. Mesh sheets of HA/PLLA were customized by a rapid
      prototyping method based on computed tomography (CT) data. Marginal resection of
      the tumor was carried out, and PCBM was harvested from the bilateral posterior
      iliac crests. PCBM and platelet-rich plasma were transferred to the tray, and the
      tray was fixed rigidly with HA/PLLA screws. In the second case, dental implants
      were inserted. There has been no bone resorption for over 2 years since
      reconstruction in these two cases, and the inserted dental implants have been
      free from any complications 1 year after loading. The average CT value in
      Hounsfield units (HU) of the implant sites of two cases was 790. In conclusion,
      the customized HA/PLLA tray was easily adapted to the mandible, and fine bone
      quality was obtained. These cases show that this tray system contributed to
      functional oral rehabilitation with dental implants.

PMID- 20155514
TI  - Rabson-Mendenhall syndrome: two case reports and a brief review of the
      literature.
AB  - Rabson-Mendenhall syndrome is a rare, autosomal recessive disorder characterized
      by insulin resistance syndrome, growth retardation, coarse and senile-looking
      faces, mental precocity, early dentition, and pineal hyperplasia. Mutations of
      the insulin receptor gene affecting insulin action appear to be the basic
      mechanism underlying this syndrome. We report on Rabson-Mendenhall syndrome in
      two siblings and briefly review the literature.

PMID- 20155515
TI  - Review of the physiology of human thermal comfort while exercising in urban
      landscapes and implications for bioclimatic design.
AB  - This review comprehensively examines scientific literature pertaining to human
      physiology during exercise, including mechanisms of heat formation and
      dissipation, heat stress on the body, the importance of skin temperature
      monitoring, the effects of clothing, and microclimatic measurements. This
      provides a critical foundation for microclimatologists and biometeorologists in
      the understanding of experiments involving human physiology. The importance of
      the psychological aspects of how an individual perceives an outdoor environment
      are also reviewed, emphasizing many factors that can indirectly affect thermal
      comfort (TC). Past and current efforts to develop accurate human comfort models
      are described, as well as how these models can be used to develop resilient and
      comfortable outdoor spaces for physical activity. Lack of suitable spaces plays a
      large role in the deterioration of human health due to physical inactivity,
      leading to higher rates of illness, heart disease, obesity and heat-related
      casualties. This trend will continue if urban designers do not make use of
      current knowledge of bioclimatic urban design, which must be synthesized with
      physiology, psychology and microclimatology. Increased research is required for
      furthering our knowledge on the outdoor human energy balance concept and
      bioclimatic design for health and well-being in urban areas.

PMID- 20155516
TI  - Chest nodule in a patient with multiple myeloma.

PMID- 20155517
TI  - A systematic review of community-based health interventions on depression for
      older adults with heart disease.
AB  - PURPOSE: This systematic review examined the effectiveness of community-based
      heart-health interventions on depression outcomes among homebound elderly (64
      years and older) with heart disease. DESIGN AND METHODS: A comprehensive
      literature search and meta analysis was performed to evaluate randomized
      controlled trials examining outpatient or home-based interventions.
      Methodological quality was assessed by standard criteria developed by the
      Cochrane Collaborative Initiative. RESULTS: Fifteen studies met our inclusion
      criteria and all measured depression outcomes. Studies differed in scope and
      methodological rigor and sample sizes varied widely. Problems in treatment
      fidelity and masking of group assignment were noted. Great variability was found
      in depression outcomes due to the differences in methodology and intervention.
      Five studies reported significant treatment effect on depression; three of those
      employed home-based interventions and two were outpatient-clinic interventions.
      Ten studies were included in the meta analysis and the effect sizes (ESs) ranged
      from -0.39 (in favor of control group) to 0.65 (in favor of treatment group). The
      mean weighted ES was 0.11 and six studies showed positive ESs. IMPLICATIONS:
      Mixed evidence for community-based heart disease interventions on depression
      outcomes was found. Future research should include sub-analysis of ESs of
      interventions on depression outcomes by different demographic characteristics of
      the study sample, common depression outcome measures, and different follow-up
      periods.

PMID- 20155518
TI  - Awareness in people with severe dementia: review and integration.
AB  - OBJECTIVE: Although awareness has been extensively researched in relation to
      people with dementia, studies have focussed mainly on people who have dementia of
      mild to moderate severity. Consequently, relatively little is known about
      awareness in people with severe dementia, and there is no clear conceptual
      framework to indicate how this should be understood or investigated. METHOD: This
      review presents a conceptual framework for considering awareness in people with
      moderate to severe dementia which distinguishes fundamental awareness of sensory
      and perceptual stimuli and three levels of awareness involving more complex
      cognitive operations, termed 'on-line monitoring', 'evaluative judgement' and
      'meta-representation', and provides an integration of the available evidence
      regarding each level. RESULTS: Findings indicate that sensory and perceptual
      awareness can be detected even in people with very severe or end-stage dementia,
      while some aspects of complex awareness may be retained into the severe stages.
      CONCLUSIONS: The environmental context and the nature of caregiving interactions
      influence the extent to which awareness is expressed. There may be scope for
      enhancing the expression of some aspects of awareness in people with moderate to
      severe dementia, but this should only be undertaken where it is likely to improve
      quality of life. Understanding more about awareness is an important element in
      the provision of high-quality care for people with moderate to severe dementia.

PMID- 20155519
TI  - Older adults' health and late-life drinking patterns: a 20-year perspective.
AB  - OBJECTIVES: This study focused on the associations between older adults' health
      related problems and their late-life alcohol consumption and drinking problems.
      METHODS: A sample of 719 late-middle-aged community residents (55-65 years old at
      baseline) participated in a survey of health and alcohol consumption and this
      survey was followed 10 years and 20 years later. RESULTS: Health-related problems
      increased and alcohol consumption and drinking problems declined over the 20-year
      interval. Medical conditions, depressive symptoms, medication use, and acute
      health events were associated with a higher likelihood of abstinence; acute
      health events were also associated with less alcohol consumption. In contrast,
      reliance on alcohol to reduce pain was linked to more alcohol consumption.
      Moreover, an individual's overall health burden and reliance on alcohol to reduce
      pain were associated with more drinking problems. Reliance on alcohol to reduce
      pain potentiated the association between health burden, alcohol consumption and
      drinking problems. CONCLUSION: Older adults who have more health problems and
      rely on alcohol to manage pain are at elevated risk for drinking problems. Health
      care providers should target high-risk older adults, such as those who drink to
      reduce pain, for screening and brief interventions to help them identify new ways
      to cope with pain and curtail their drinking.

PMID- 20155520
TI  - Supporting the dementia family caregiver: the effect of home care intervention on
      general well-being.
AB  - OBJECTIVES: Although high volumes of literature have been written on
      interventions in dementia home care, only a poor efficiency has been proved.
      Nevertheless, caregivers often express strong feelings of satisfaction about the
      proposed support. In this meta-analytic review, a quantitative analysis of the
      effect of the different types of professional dementia home care interventions
      was made. METHOD: A systematic literature search, covering the years 1980 until
      2007, was performed using Medline, Embase, Cochrane DSR, Dare, CCTR, and ACP
      Journal Club). Limitations on publication type were determined as randomized
      controlled trial and controlled trial. RESULTS: Psychosocial intervention in
      dementia home care was found to be beneficial in a non-significant way on
      caregivers' burden. An almost negligible decrease in depression was found in the
      psychosocial intervention arm while multidisciplinary case management contributed
      to a larger though insignificant decrease of depression in caregivers. Respite
      care was responsible for an increase in burden. CONCLUSION: This review
      demonstrated, in accordance with other qualitative reviews, the weak evidence
      that supporting family caregivers could be beneficial. Although the rather small
      benefits of formal support, supporting family caregivers is an indispensable
      issue in dementia home care. Professional caregivers should keep in mind that
      family caregivers highly appreciate the intervention and that they feel less
      burdened or depressed in the short time follow up but that premature home care
      remains more rule than exception.

PMID- 20155521
TI  - Worries, psychosocial resources, and depressive symptoms among the South Korean
      oldest old.
AB  - OBJECTIVES: Few Korean studies have explored factors that influence depressive
      symptoms, a condition that is likely to increase with age. This study examines
      how worries, psychosocial resources, specifically family support, are related to
      depressive symptoms among a sample of the oldest old in South Korea. The
      buffering effects of psychosocial resources previously identified as reducing the
      impact of worries on depression in the younger old age group were also examined.
      METHOD: Interviews were conducted with 213 community-dwelling oldest old in
      Seoul, Korea in 2007. 193 of these had children and were included in the
      analysis. Multiple regression analysis was used to test the hypotheses. RESULTS:
      Greater worries were significantly related to greater severity of depressive
      symptoms among South Korean oldest old. Psychosocial resources including mastery,
      emotional support from adult children, and instrumental support from adult
      children had main effects on depressive symptoms. Emotional support from adult
      children had a powerful buffering effect on the relationship between worries and
      depressive symptoms. CONCLUSION: Worries and certain aspects of social support
      are important in understanding the depressive symptoms of South Korean oldest
      old. Incorporating filial support into the development of services for this age
      group could be helpful to treating their symptoms of depression.

PMID- 20155522
TI  - The impact of past and present preferences on stimulus engagement in nursing home
      residents with dementia.
AB  - OBJECTIVES: We examined engagement with stimuli in 193 nursing home residents
      with dementia. We hypothesized that activities and stimuli based on a person's
      past and current preferences would result in more engagement than other
      activities/stimuli. METHOD: The expanded version of the self-identity
      questionnaire [Cohen-Mansfield, J., Golander, H. & Arheim, G. (2000)] was used to
      determine participants' past/present interests (as reported by relatives) in the
      following areas: art, music, babies, pets, reading, television, and office work.
      We utilized the observational measurement of engagement (Cohen-Mansfield, J.,
      Dakheel-Ali, M., & Marx, M.S. (2009). RESULTS: Analysis revealed that residents
      with current interests in music, art, and pets were more engaged by stimuli that
      reflect these interests than residents without these interests. CONCLUSION: Our
      findings demonstrate the utility of determining a person's preferences for
      stimuli in order to predict responsiveness. Lack of prediction for some stimuli
      may reflect differences between past preferences and activities that are feasible
      in the present.

PMID- 20155523
TI  - A cross-sectional population-based study of elder self-neglect and psychological,
      health, and social factors in a biracial community.
AB  - OBJECTIVE: Elder self-neglect is an important public health issue; however, its
      association with psychological, health, and social factors remains unclear. This
      study aimed to (1) examine the associations between self-neglect severity and
      psychological, health, and social factors (2) examine the racial/ethnic
      differences in these associations. METHODS: We conducted a biracial population
      based study in a geographically defined community in Chicago: Chicago Health
      Aging Project. We identified 1094 persons who had been identified by social
      services agency as suspected elder self-neglect from 1993 to 2005. Self-neglect
      severity was assessed on a 0-45 scale. The psychological, health, and social
      factors were assessed using Center for Epidemiological Studies of Depression
      (CESD), poor mental health, health status, unhealthy days, poor physical health,
      days away from usual activities, social network, and social engagement. Linear
      regression was used to assess associations between self-neglect and
      psychological, health, and social factors. Interaction terms (Self-neglect x
      Race) were used to assess the black (non-Hispanic black) and white (non-Hispanic
      white) differences in these associations. RESULTS: There were significant
      associations between self-neglect severity with health and social factors. After
      adjusting for confounders, greater self-neglect severity was associated with
      lower health status (PE = 0.001, p = 0.002), higher unhealthy days (PE = 0.139, p
      < 0.001), poor physical health (PE = 0.141, p < 0.001), and more days away from
      usual activities (PE = 0.120, p = 0.030). Interaction term (Self-Neglect x Race)
      indicates black compared with white older adults, had more days away from usual
      activities (PE = 0.321, p = 0.045) and lower social engagement (PE = -0.04, p =
      0.003). CONCLUSION: Greater self-neglect severity is associated with lower levels
      of health and social wellbeing. These associations may be stronger for black than
      white older adults.

PMID- 20155524
TI  - Antidementia drugs: prescription by level of cognitive impairment or by socio
      economic group?
AB  - OBJECTIVES: We aimed to investigate for the first time whether cholinesterase
      inhibitor prescription was associated with economic status in a population of
      people with dementia. METHOD: We recruited 215 people with dementia, living
      independently, who were consecutively referred to five Community Mental Health
      Teams in London and Essex. We tested our hypothesis that home owners were more
      likely to be prescribed cholinesterase inhibitors than those who rented their
      accommodation. RESULTS: People who owned their home were four times more likely
      to be prescribed cholinesterase inhibitors (OR 4.2, 1.8-9.8; p = 0.001). Younger
      age, fewer neuropsychiatric symptoms, having a dementia diagnosis for which
      cholinesterase inhibitors were recommended and longer time since diagnosis also
      predicted prescription, but severity of cognitive impairment did not. CONCLUSION:
      Despite high-profile guidelines that NHS cholinesterase prescribing should be
      restricted to people with moderate dementia, being a home owner was a strong
      predictor of prescription, while dementia severity was not. We recommend that
      health services should be audited to ensure that access to treatment increases in
      those who are socioeconomically disadvantaged.

PMID- 20155525
TI  - Twelve-month prevalence of DSM-IV mental disorders among older Asian Americans:
      comparison with younger groups.
AB  - Based on public-use data from the National Latino and Asian American Study
      (NLAAS), 2002-2003, we examined the 12-month prevalence rates of any depressive,
      anxiety, or intermittent explosive disorder among older Asian Americans and
      compared them to those among younger cohorts. The 12-month prevalence rate among
      older adults, 7.4% in the 60+ group, was significantly lower than those among
      younger groups. We also found that correlates of mental disorder were not the
      same among different age groups. Among the 60+ group, ethnicity, work status,
      years in the United States, family conflict, and social disability score were the
      significant covariates of a diagnosis of mental disorder. The findings appear to
      suggest that, compared with younger cohorts, older Asian Americans may have lower
      reactivity to life stressors and/or more adaptive coping strategies.

PMID- 20155526
TI  - Age and education effects and norms on a cognitive test battery from a population
      based cohort: the Monongahela-Youghiogheny Healthy Aging Team.
AB  - OBJECTIVES: Performance on cognitive tests can be affected by age, education, and
      also selection bias. We examined the distribution of scores on several cognitive
      screening tests by age and educational levels in a population-based cohort.
      METHOD: An age-stratified random sample of individuals aged 65+ years was drawn
      from the electoral rolls of an urban US community. Those obtaining age and
      education-corrected scores > or = 21/30 on the Mini-Mental State Examination
      (MMSE) were designated as cognitively normal or only mildly impaired, and
      underwent a full assessment including a battery of neuropsychological tests.
      Participants were also rated on the Clinical Dementia Rating (CDR) scale. The
      distribution of neuropsychological test scores within demographic strata, among
      those receiving a CDR of 0 (no dementia), are reported here as cognitive test
      norms. After combining individual test scores into cognitive domain composite
      scores, multiple linear regression models were used to examine associations of
      cognitive test performance with age and education. RESULTS: In this cognitively
      normal sample of older adults, younger age and higher education were associated
      with better performance in all cognitive domains. Age and education together
      explained 22% of the variation of memory, and less of executive function,
      language, attention, and visuospatial function. CONCLUSION: Older age and lesser
      education are differentially associated with worse neuropsychological test
      performance in cognitively normal older adult representatives of the community at
      large. The distribution of scores in these participants can serve as population
      based norms for these tests, and can be especially useful to clinicians and
      researchers assessing older adults outside specialty clinic settings.

PMID- 20155527
TI  - Correlation between loneliness and social relationship among empty nest elderly
      in Anhui rural area, China.
AB  - OBJECTIVE: To study the possible associations between loneliness and social
      relationship (social support and family function) in Chinese empty nest elderly.
      METHODS: A sample of 1144 empty nest elderly were surveyed using the University
      of California at Los Angeles (UCLA)-Loneliness Scale, the Social Support Rate
      Scale and the Family Adaptability, Partnership, Growth, Affection and Resolve
      (APGAR) Index. RESULTS: The present study revealed that the majority (80.94%) of
      empty nest elderly had moderate to high levels of loneliness, with a mean score
      of 42.84 and a standardized score of 53.55. The level of loneliness was
      significantly different in subjects' age, marital status and income, but not in
      sex and education level. Social support and family function were significant
      negatively associated with loneliness. Multiple regression revealed that less
      social support and poor family function were associated with more loneliness.
      CONCLUSIONS: Loneliness prevails among empty nest elderly. It may limit empty
      nest elderly's ability or access to social relationship. These findings support
      the hypothesis that if empty nest elderly are better supported and cared for,
      their negative psychosocial consequences might be prevented or at least reduced.

PMID- 20155528
TI  - Integrating unmet needs into dementia health-related quality of life research and
      care: Introduction of the Hierarchy Model of Needs in Dementia.
AB  - OBJECTIVES: To make an inventory of needs assessment instruments in dementia, to
      explore the interaction between unmet needs and health-related quality of life
      (HRQoL) and to relate these to the conceptual model of Maslow's Hierarchy of
      needs in order to design a dementia-specific model. METHODS: Narrative review of
      literature on (measures of) needs of patients and caregivers and HRQoL
      determinants important in dementia. Relating these needs to individual goal
      setting instruments and Maslow's Hierarchy of needs model. RESULTS: The
      Camberwell Assessment of Needs for the Elderly (CANE) turns out to be a valid
      tool to assess needs of dementia patients, suitable for research and clinical
      use. The Carers' Needs Assessment for Dementia (CNA-D) is a valid instrument to
      assess needs of caregivers. Patients identified significantly fewer needs than
      (in)formal caregivers. The most important needs, that also determine large part
      of HRQoL, are need for information; support with regard to symptoms of dementia;
      social contact and company; and for health monitoring and safety. Goal attainment
      scaling in dementia is an important but not yet valid outcome measure, with only
      few data on feasibility in dementia patients. CONCLUSION: There are several
      instruments to assess needs of dementia patients and caregivers. Domains of unmet
      needs and HRQoL overlap. The Hierarchy Model of Needs in Dementia (HMND) offers a
      new theoretical framework to address the interplay between meeting of needs and
      improvement of HRQoL in dementia. By identifying unmet needs in dementia-research
      and focussing on unmet needs in dementia-care, much can be done to improve HRQoL.

PMID- 20155529
TI  - Rearing histories of individuals with and without social anxiety who become first
      time parents.
AB  - The effect of rearing history on future parents' social anxiety was studied by
      means of retrospective reports. The research sample consisted of 121 couples who
      were expecting their first child. Social anxiety was assessed both as a
      continuous trait using the Short Social Phobia and Anxiety Inventory, and as a
      disorder using the Anxiety Disorder Interview Schedule. Men and women rated their
      father's and mother's encouragement of autonomy (versus overprotection) and
      acceptance (versus rejection) on the Mother-Father-Peer Inventory. Analyses
      taking into account within-couple dependency indicated that there were no
      differences between men and women in the relation between rearing history and
      social anxiety. Results showed that participants who rated their mother higher on
      rejection, and those rating their father higher on overprotection, scored higher
      on self-reported social anxiety. Perceived lower encouragement of autonomy by
      mothers predicted social anxiety disorder (SAD) but not other non-social anxiety
      disorders, whereas perceived lower encouragement of autonomy by fathers predicted
      other anxiety disorders, but not SAD. It is concluded that mothers and fathers
      may play different roles in the etiology of anxiety.

PMID- 20155530
TI  - Patterns of actual and perceived control: are control profiles differentially
      related to internalizing and externalizing problems in youth?
AB  - This study provided an initial test of a theoretical model which emphasizes
      patterns of actual and perceived control. The model suggests that profiles of
      actual and perceived control are differentially related to emotional and
      behavioral problems. We examined whether anxiety and depression symptoms and
      aggressive behavior would differ among diverse patterns of actual (caregiver
      reported competencies) and perceived control (anxiety-related control beliefs) in
      youth (n=203). Results were consistent with the theoretical predictions in that
      reported levels of anxiety and depression symptoms and aggressive behavior varied
      depending upon youth's control profiles. For example, youth with high actual and
      low perceived control exhibited relatively more anxiety/depression symptoms than
      aggressive behavior, while those youth with low actual and high perceived control
      exhibited relatively more aggressive behavior. Furthermore, youth with both high
      actual and perceived control reported and were reported by caregivers as having
      the least anxiety/depression symptoms and aggressive behavior, respectively. The
      findings provide empirical support for the model and suggest the importance of
      considering the role of actual and perceived control in emotional and behavioral
      problems. Implications for future tests of the model are also discussed.

PMID- 20155531
TI  - MRI image-based FE modelling of the pelvis system and bladder filling.
AB  - In this study, high-resolution magnetic resonance imaging was performed in the
      transaxial, coronal and sagittal planes to provide comprehensive structural
      details of the bladder and surrounding systems. Detailed finite-element (FE)
      models that were specific to each participant were developed by rendering the
      images, and the process of bladder filling was simulated. The overall model of
      bladder deformation was compared with repeated images of the filled bladder that
      were obtained using computed tomography to validate the FE models. The
      relationship between the changes in the key dimensions of the bladder and the
      increase in bladder volume during the filling process was also investigated. The
      numerical results showed that the bladder dimensions increased linearly with its
      volume during the filling process and the predicted coefficients are comparable
      to some of the published clinical results.

PMID- 20155532
TI  - Youth or disadvantage? The construction of teenage mothers in medical journals.
AB  - Teenage motherhood is routinely discussed in medical and nursing journals as a
      cause for concern and a social problem. Taking these accounts as a starting
      point, this paper uses discursive analysis to understand how the teenage mother
      is produced as an unsuitable mother. Beginning with a 'Public Health' discourse,
      early motherhood is understood as a disease requiring surveillance and a public
      health response. Using an 'Economic' discourse, teenage mothers are positioned as
      a financial drain on society and early motherhood as a cost to the mothers
      themselves. An 'Ethnicity' discourse classifies young mothers into ethnic groups
      and explains differential fertility rates through the resistance of appropriate
      reproductive technology among minority group members. These understandings are
      reflected in a 'Eugenics' discourse, which engages metaphors of parenting as a
      biological priority and highlights the unsuitability of young mothers as parents.
      An examination of these discourses shows that concern about teenage motherhood is
      as much about the wrong sort of young women becoming mothers, as mothering too
      soon.

PMID- 20155533
TI  - Rapid and advanced tools for mycotoxin analysis: a review.
AB  - The problems associated with mycotoxin contamination of foods and feeds are well
      established and, in many cases, have been known for a long time. Consequently,
      the techniques for detecting known mycotoxins are quite advanced and range from
      methods for directly detecting the toxins themselves, based upon physical
      characteristics of the toxins, to methods for indirectly detecting the toxins,
      such as immunoassays. This review focuses on recent technologies that can be used
      to detect mycotoxins and, as such, is not a comprehensive review of the mycotoxin
      analytical literature. Rather, the intent is to survey the range of technologies
      from those that are instrument intensive such as modern chromatographic methods
      to those that require no instrumentation, such as certain immunoassays and
      biosensors. In particular, mass spectrometric techniques using ambient ionization
      offer the intriguing possibility of non-destructive sampling and detection. The
      potential application of one such technique, desorption electrospray ionization
      (DESI), is demonstrated for fumonisin B(1) on maize. While methods for detecting
      mycotoxins are quite advanced, the need remains for assays with increased
      throughput, for the exploration of novel detection technologies, and for the
      comprehensive validation of such technologies as they continue to be developed.

PMID- 20155534
TI  - Characterization, antigenicity and detection of fish gelatine and isinglass used
      as processing aids in wines.
AB  - Fish gelatine (FG) and isinglass (IG) are widely used in the pharmaceutical
      industry and as ingredients or processing aids in food production. Both products
      are the focus of interest since several countries, particularly the member states
      of the EU and Japan, USA, Australia and New Zealand, have introduced special
      labelling regulations for allergenic foodstuffs, such as fish and products
      thereof. Thus, there is a demand for a reliable and sensitive method for the
      detection of FG and IG in foodstuffs. In this study, the characterization of
      various FGs and IGs, polyclonal antibodies raised against fish collagen and the
      development of a sensitive indirect ELISA for the detection of FG and IG is
      described. The ELISA method detected < or =0.11 microg ml(-1) from all FGs and
      IGs tested. The indirect ELISA was applied to various experimental wines where FG
      and IG had been used as processing aids and to several commercial wines. No
      residues of FG and IG were detected in the experimental wines additionally
      treated with bentonite, a strong adsorbent for proteins, and successive
      filtration. Additionally, no residues were found in the commercial wines.
      However, amounts of up to 0.33 microg ml(-1) were found in some experimental
      wines not treated with bentonite and successive filtration. Therefore, wines may
      contain traces of FG and IG that were used as processing aids during wine
      production. However, treatment with bentonite in combination with additional
      filtration had a clear impact on these residues.

PMID- 20155535
TI  - Furan in coffee: pilot studies on formation during roasting and losses during
      production steps and consumer handling.
AB  - The occurrence of furan in some food products has already been known for a few
      decades, and it has been reconfirmed in more recent investigations that furan is
      present in a variety of foodstuffs. This list of products includes roasted
      coffee, which has been shown to generate furan as a result of the heat treatment
      at roasting which is applied to achieve the desired aroma and flavour profile of
      a roasted coffee. The objective of this study is to provide data to allow a
      better understanding of the available data of furan in coffee, the kinetics of
      furan generated during roasting, and to estimate the reduction of furan levels
      afterwards due to subsequent processing steps and consumer handling. Finally, the
      study is meant as a contribution to establish exposure data on the basis of
      scientific data at the stage of coffee consumption. This paper shows that the
      formation of furan during roasting is dependent on roasting conditions and is,
      therefore, directly linked to achieving targeted flavour profiles. Furthermore,
      it is demonstrated that modifications in process conditions potentially to reduce
      furan levels may have the opposite effect on other undesired reaction products of
      the roasting chemistry such as, for example, acrylamide. Due to the high
      volatility of furan, any subsequent processing step or consumer handling has an
      impact on the level of furan. As a guidance from this study and in consideration
      of the identified losses of each process and handling step on the basis of the
      trial conditions, it is estimated that only approximately 10% of the initially
      generated furan during roasting gets into the cup of coffee for consumption.

PMID- 20155536
TI  - Physiologically based pharmacokinetic (PBPK) model for residues of lipophilic
      pesticides in poultry.
AB  - Physiologically based pharmacokinetic (PBPK) modelling has been used to examine
      the relative importance of physiological differences between laying hens and
      broiler chickens as well as between broiler chickens and ducks, geese, and
      turkeys in determining tissue residues. Following exposure in feed, there may be
      significant differences in tissue residues between laying hens and broiler
      chickens. The blood lipid content of laying versus broilers, the duration of
      exposure, and the fraction of the dose absorbed into the systemic circulation
      were important parameters together with tissue-to-blood partition coefficients.
      The potential for modelling to improve the extrapolation of residue transfer
      studies carried out using laying hens to broiler chickens and other poultry is
      demonstrated.

PMID- 20155537
TI  - Predicted intake of trace elements and minerals via household drinking water by 6
      year-old children from Krakow, Poland. Part 5: Zinc.
AB  - Zinc (Zn) exposure in pre-school children via household drinking water collected
      by a double sampling method (morning, evening) was evaluated in a sample of the
      Polish population. Zn concentration was measured by flame atomic absorption
      spectrometry. Rural and suburban Krakow sites were non-distinguishable in respect
      of Zn concentrations. However, significantly lower Zn was found in urban as
      compared with non-urban sites [geometric mean (95% confidence interval) 0.14
      (0.01-1.95) mg l(-1) versus 0.52 (0.03-10.2) mg l(-1), p < 0.001.] Zn levels in
      water standing overnight in pipelines were higher in all sites by 0.36 mg l(-1)
      on average, but observed really contaminations were higher. The Zn limit based on
      the taste and colour of drinking water (3 mg l(-1)) was exceeded in 1% and 10% of
      households from urban and non-urban sites, respectively. The Zn intake
      predictions for evening water samples for 6-year-old children averaged between 2%
      and 9% of the recommended dietary allowance (RDA, 10 mg day(-1)) for urban and
      non-urban sites, respectively. Mean Zn intake prediction for the exceedance
      fraction was 64% of RDA. In conclusion, overnight contamination of drinking water
      from in-house pipelines was significant and common to all sites investigated.
      Secondly, drinking water can be considered a significant contributor to dietary
      Zn intake by children in non-urban sites and may shift the population borderline
      of deficiency.

PMID- 20155538
TI  - Mercury and methylmercury bioaccessibility in swordfish.
AB  - Concentrations of mercury (Hg) in swordfish (Xiphias gladius) present a food
      safety problem for many countries. This study analyses total Hg (t-Hg)
      concentrations in 27 samples of swordfish marketed in Spain in 2005 and in their
      bioaccessible fractions (soluble concentration in gastrointestinal medium),
      obtained after applying an in vitro digestion method. Methylmercury (MeHg) was
      also determined in the bioaccessible fractions. t-Hg concentrations in the
      samples were 0.41-2.11 mg kg(-1) wet weight, with a mean of 0.96 +/- 0.47 mg kg(
      1) wet weight. A total of 37% of the samples exceeded the Hg limit set by Spanish
      legislation (1.0 mg kg(-1) wet weight). Bioaccessible t-Hg concentrations were
      0.17-1.72 mg kg(-1) wet weight (0.63 +/- 0.4 mg kg(-1) wet weight), corresponding
      to 38-83% (64% +/- 14%) of t-Hg. Bioaccessible MeHg concentrations, representing
      94% of the bioaccessible t-Hg concentrations, were 0.16-1.53 mg kg(-1) wet
      weight, with a mean of 0.49 +/- 0.32 mg kg(-1) wet weight. Children and adults
      who regularly consume this product in Spain have Hg and MeHg intakes that exceed
      the tolerable daily intake limits recommended by the Food and Agricultural
      Organization/World Health Organization (FAO/WHO) and US Environmental Protection
      Agency (USEPA). These results show the need for recommendations about swordfish
      consumption by population groups at risk in Spain.

PMID- 20155539
TI  - Development of chemiluminescence enzyme-linked immunosorbent assay for the
      screening of metolcarb and carbaryl in orange juice, cabbage and cucumber.
AB  - A direct competitive enzyme-linked immunosorbent assay (ELISA) with enhanced
      chemiluminescent detection for simultaneous detection of metolcarb and carbaryl
      in agricultural products is reported. The concentrations of coating antibodies
      and enzyme tracer, as well as the effects of pH and methanol concentrations, were
      investigated. Under optimum conditions, the IC(50) of metolcarb and carbaryl were
      4 and 0.3 microg kg(-1), respectively. Detection of metolcarb and carbaryl in
      fruit juices and vegetables was accomplished using simple, rapid and efficient
      extraction methods. Recoveries (n = 3) of spiked samples ranged 75-108% for
      metolcarb and 74-98% for carbaryl. Validation of the enhanced chemiluminescent
      immunosorbent assay was conducted by comparison of results with HPLC. The
      correlation between the data obtained using ELISA with enhanced chemiluminescent
      detection and HPLC was good (n = 9). Therefore, the enhanced chemiluminescent
      ELISA was suitable for quantitative simultaneously determination of metolcarb and
      carbaryl residue in agricultural products.

PMID- 20155540
TI  - A new tool for the evaluation of crop residue trial data (day-zero-plus decline).
AB  - An approach is presented for the prediction of pesticide residue concentrations
      in food and feed commodities produced from foliar-treated crops. It uses limited
      residue trial data and relies on information on spray retention and decline rates
      of residues following application. The use of the simple approach is demonstrated
      for residues of a variety of pesticides and the results compared with data sets
      evaluated by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) using expert
      judgement and also with estimates of high residues obtained using statistical
      methods. It is proposed that the approach should constitute an additional tool
      for the risk assessment of pesticide residues; it contributes to the estimation
      of maximum residue limits (MRLs) and high and median residues, which are needed
      for risk assessment. The approach should be particularly useful in situations
      where only a few residue trials are available such as often occurs for minor
      crops.

PMID- 20155541
TI  - Exposure to aflatoxins in Japan: risk assessment for aflatoxin B1.
AB  - The intake of total aflatoxins (AFT) and aflatoxin B(1) (AFB(1)) from food in
      Japan was estimated from AFT and AFB(1) concentration and frequency data in 24
      foods (884 samples) from a 3-year retail market survey from the summer of 2004 to
      the winter of 2006, and by food consumption data from the National Health and
      Nutrition Survey performed in 2005. The AFT and AFB(1) survey revealed that
      peanut, peanut products, cocoa, chocolate, pistachio, white pepper, red pepper,
      almond, job's tears, buckwheat and corn grits are considered to be contributors
      of AFT (or AFB(1)) intake in Japan (maximum AFB(1) (AFT) levels ranged from 0.21
      to 28.0 microg kg(-1) (from 0.21 to 9.0 microg kg(-1))) in AFT-contaminated food.
      A probabilistic approach using the Monte Carlo method was carried out to simulate
      an estimate of the AFT (or AFB(1)) intake distributions in each age group in
      Japan. In this study, AFB(1) intake ranged from 0.003 to 0.004 ng kg(-1) body
      weight day(-1) (from lower to upper limits), and the potential risk for cancer
      using a formula devised by the Joint Food and Agricultural Organization/World
      Health Organization (FAO/WHO) Expert Committee on Food Additives (JECFA) was
      estimated at 0.00004-0.00005 person/year/100,000 persons, even though this was in
      the higher levels (95.0th percentile) of the consumer population. The results
      suggest that the current dietary intake of AFB(1) in Japan has no appreciable
      effect on health.

PMID- 20155542
TI  - Naturally occurring aflatoxin M(1) in raw bulk milk from farm cooling tanks in
      Argentina.
AB  - The aim was to carry out a survey of aflatoxin M(1) (AFM(1)) in raw whole milk
      from bulk tanks. The sample collection was performed in farms located in one the
      most important milk-production zones in the centre of Argentina. A total of 94
      samples of milk from 47 dairy farms were analysed. AFM(1) analysis involved the
      use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) with prior
      purification of the extracts using immunoaffinity columns. AFM(1) incidence in
      raw milk was high as 63.8% and levels were between not detected to 0.07 microg l(
      1). Several contaminated samples (39%) were over the European Commission limit
      for infant milk (0.025 microg l(-1)), although none of samples were above
      Argentine legislation. Estimates of AFM(1) intake were assessed for different age
      populations. The average AFM(1) estimated daily intakes were 1.6, 0.5, 0.17 ng
      kg(-1) body weight day(-1) for 4-year-old babies, young children, and adults,
      respectively. All tested farms used pastures and silages at similar composition.
      Even though some farms (13) employed high-risk supplementary feeds, such as
      peanut pod and/or cotton seed, no statistically significant differences were
      observed between groups. Information from AFM(1) levels in milk in Argentina is
      limited. A systematic AFM(1) monitoring programme must be performed by means of
      accurate and reliable analytical techniques as a strategy for protecting milk
      consumers.

PMID- 20155543
TI  - Health system reconstruction: Perspectives of Iraqi physicians.
AB  - In conflict or post-conflict situations, health system reconstruction becomes a
      critical component of ensuring stability. The purpose of this study was to
      determine the priorities for health system reconstruction among Iraqi physicians
      residing in the northern region of the country. A convenience sample of
      practicing male and female physicians residing in the Kurdish region completed a
      13-item survey about health system reconstruction. A total of 1001 practitioners
      completed the survey with gender breakdown of 29% female and 71% male, all
      working in different specialty areas. Significant differences between the
      providers based on gender (p=0.001), specialty (p=0.001) and geographic location
      (p=0.004) were found to affect the responses of the participants. This study
      demonstrates that input from healthcare professionals is important for health
      system reconstruction, but that gender, geography and medical specialty make the
      process complex.

PMID- 20155544
TI  - Vietnam moves forward with harm reduction: an assessment of progress.
AB  - Historically, the response of the Vietnamese government to illicit drug use and
      HIV has been slow and ineffective. However, 2006 saw the government formally
      endorse harm reduction interventions. This paper examines the views of senior key
      informants inside Vietnam on the development of an advocacy strategy for harm
      reduction. Twenty-nine informants were interviewed across public health, public
      security, social affairs and other international bodies, including United Nations
      agencies and international non-governmental organisations. Challenges and
      barriers identified for harm reduction progress included: promoting a nationwide
      understanding and acceptance of harm reduction and the HIV Law; lack of skilled
      resources, training programmes and technical capacity; poor coverage of
      interventions; and gaps in the sharing of information. There is currently a
      government-led shift in Vietnam in the response to the prevailing HIV epidemic
      among drug users, but ensuring that the HIV Law can operate unhindered is
      critical. The implementation of a response to illicit drug use and HIV remains an
      enormous challenge. With appropriate technical education and training, ongoing
      advocacy, and a cohesive, coordinated multi-sectoral effort, the capacity of the
      government and community to adopt, support and promote measures to reduce HIV and
      other drug-related harms will be markedly strengthened.

PMID- 20155545
TI  - Religious leaders' response to AIDS in Nigeria.
AB  - Increasingly, faith-based organisations are being asked to participate in HIV
      prevention and care activities. This paper presents formative research on
      HIV/AIDS prevention messages, activities and policies within six religious
      institutions in Cross River State, Nigeria, at urban and rural sites. Data
      collection methods included a review of written HIV policies gathered from
      national church and mosque offices and 48 key informant interviews. The study
      highlights differences in messages between mainstream and Pentecostal Christians
      and Muslims. Although all groups stated a core message of abstinence outside
      marriage and faithfulness within marriage, Pentecostal churches tended to have
      more messages of punishment and condemnation for people infected with HIV. Urban
      churches/mosques tended to have more HIV resources and programmes. Attitudes
      towards condom use varied by denomination and individual; although few saw a role
      for religious institutions to promote condoms there were exceptions voiced. These
      findings indicate that religious organisations are already playing a role in HIV
      prevention but their responses are not uniform. Public health organisations and
      policy-makers should be aware of these denominational differences as they engage
      with religious institutions and leaders in HIV prevention and care.

PMID- 20155546
TI  - Eliminating cataract blindness - how do we apply lessons from Asia to sub-Saharan
      Africa?
AB  - The VISION 2020 initiative aims to eliminate avoidable blindness by the year
      2020. Cataract, the main cause of blindness and other visual impairment, is a
      main focus of this effort. In India, the Aravind Eye Care System provides an
      impressive model demonstrating how high quality eye care, including cataract
      surgery, can be delivered to large numbers and made affordable to all. Similarly,
      financially self-supporting systems have not been developed at this point in sub
      Saharan Africa. This paper explores the factors that lead to success at Aravind,
      and compares and contrasts the conditions in India with those found in much of
      sub-Saharan Africa.

PMID- 20155547
TI  - Developing WHO guidelines with pragmatic, structured, evidence-based processes: A
      case study.
AB  - Many guidelines, including those produced by the World Health Organisation (WHO),
      have failed to adhere to rigorous methodological standards. Operational examples
      of guideline development processes may provide important lessons learned to
      improve the rigour and quality of future guidelines. To this end, this paper
      describes the process of developing WHO guidelines on prevention and care
      interventions for adults and adolescents living with HIV. Using a pragmatic,
      structured, evidence-based approach, we created an organising committee,
      identified topics, conducted systematic reviews, identified experts and
      distributed evidence summaries. Subsequently, 55 global HIV experts drafted and
      anonymously submitted guideline statements at the beginning of a conference.
      During the conference, participants voted on statements using scales evaluating
      appropriateness of the statements, strength of recommendation and level of
      evidence. After review of voting results, open discussion, re-voting and
      refinement of statements, a draft version of the guidelines was completed. A post
      conference writing team refined the guidelines based on pre-determined guideline
      writing principles and incorporated external comments into a final document.
      Successes and challenges of the guideline development process were identified and
      are used to highlight current issues and debates in developing guidelines with a
      focus on implications for future guideline development at WHO.

PMID- 20155548
TI  - Using lifestyle analysis to develop wellness marketing strategies for IT
      professionals in India.
AB  - Revenues for the information technology (IT) industry have grown 10 times over
      the past decade in India. Although this growth has resulted in increased job
      opportunities, heavy workloads, unhealthy eating habits, and reduced family time
      are significant downfalls. To understand lifestyle choices of IT professionals,
      this study segmented and profiled wellness clients based on lifestyle. Data were
      collected from clients of five wellness centers. Cluster and discriminant
      analyses revealed four wellness consumer segments based on lifestyle. Results
      indicated a need for varying positioning approaches, segmentation, and marketing
      strategies suited for identified segments. To assist managers of wellness
      centers, four distinct packages were created that can be marketed to clients in
      the four segments.

PMID- 20155549
TI  - Sensation seekers as a healthcare marketing metasegment.
AB  - This article discusses "sensation seekers" as a market segment for communication
      and prevention programs for various lifestyle and/or risk-related health problem
      areas such as alcohol abuse, drug abuse, suicide attempts, and sexually
      transmitted diseases. Although sensation seekers tend to be creative, artistic
      individuals, they are also prone to various negative health behaviors and many
      population-based prevention programs have over-looked these individuals as an
      important target. Various inputs to sensation-seeking causation are explored,
      including biological/chemical, psychological, and the impact of external
      characteristics. Using a combination for regulatory focus and risk homeostasis,
      propositions are provided for improving the effectiveness of the communications.
      Recommendations for prevention efforts focusing on reaching this subculture using
      television, along with other electronic media are proposed, including
      recommendations for message construction and presentation venues.

PMID- 20155550
TI  - Stakeholders' views of service quality in community pharmacy: a qualitative
      study.
AB  - This study investigates the views of a range of stakeholders regarding the
      effectiveness of service quality as a differentiating position for community
      pharmacy. Using qualitative methodology, 20 in-depth interviews were conducted
      with various stakeholders of the retail pharmacy market, including community
      pharmacists. It was found that current service levels were perceived to be
      variable, with a strong level of concern evident that the rhetoric of
      professionalism in community pharmacy is not always matched by the reality. There
      was disagreement regarding whether potential market entrants such as supermarkets
      would be capable of delivering a high quality of service and indeed whether that
      would even be their objective.

PMID- 20155551
TI  - Preventing fetal alcohol spectrum disorders: the role of protection motivation
      theory.
AB  - This article examines health communication campaigns aimed at preventing alcohol
      consumption among women who are pregnant or attempting to become pregnant.
      Relevant communication materials were gathered and a qualitative review was
      conducted. A majority of the campaigns followed the tenets of protection
      motivation theory by focusing on the threat variables of severity and
      vulnerability, as well as emphasizing response efficacy. Few campaigns focused on
      costs or self-efficacy. Future fetal alcohol spectrum disorders prevention
      initiatives should attempt to reduce perceived costs, as well as include self
      efficacy messages in order to increase women's confidence that they can carry out
      the recommended actions.

PMID- 20155552
TI  - Customer advisory groups: another way to listen to the marketplace.
AB  - Customer advisory groups (CAGs) are formal groups of customers (referring
      physicians, patients, health insurance brokers, etc.) who meet regularly to share
      their ideas and to provide feedback to proposed or existing marketing strategies,
      programs, and activities. While CAGs are very prevalent in other industries they
      appear to be relatively underutilized in health care. This article provides an
      overview of how CAGs work, their advantages and disadvantages, tips on how to
      make them work better, and insights from interviews with 39 healthcare chief
      marketing officers on their use of CAGs.

PMID- 20155553
TI  - Altruistic, cognitive and attitudinal determinants of organ donation intention in
      Egypt: a social marketing perspective.
AB  - This study investigates the influence of various altruistic, cognitive, and
      attitudinal factors on the organ donation intention in Egypt. Using a large
      sample, a conceptual model has been developed. The findings from the structural
      equation model confirm the influence of the respondents' altruistic values,
      perceived benefits and risks, and knowledge on their attitudes towards organ
      donation. Respondents' attitudes towards organ donation, in turn, are also found
      to affect their organ donation intention. One of the other important findings
      suggests that on a declarative level, more and more individuals in Egypt express
      their concern over the shortage of available organs and declare their willingness
      to contribute somehow to alleviate the problem. However, in reality this concern
      may not be manifested consistently.

PMID- 20155554
TI  - Visualizing desirable patient healthcare experiences.
AB  - High healthcare cost has drawn much attention and healthcare service providers
      (HSPs) are expected to deliver high-quality and consistent care. Therefore, an
      intimate understanding of the most desirable experience from a patient's and/or
      family's perspective as well as effective mapping and communication of such
      findings should facilitate HSPs' efforts in attaining sustainable competitive
      advantage in an increasingly discerning environment. This study describes (a) the
      critical quality attributes (CQAs) of the experience desired by patients and (b)
      the application of two visualization tools that are relatively new to the
      healthcare sector, namely the "spider-web diagram" and "promotion and detraction
      matrix." The visualization tools are tested with primary data collected from
      telephone surveys of 1,800 patients who had received care during calendar year
      2005 at 6 of 61 hospitals within St. Louis, Missouri-based, Ascension Health.
      Five CQAs were found by factor analysis. The spider-web diagram illustrates that
      communication and empowerment and compassionate and respectful care are the most
      important CQAs, and accordingly, the promotion and detraction matrix shows those
      attributes that have the greatest effect for creating promoters, preventing
      detractors, and improving consumer's likelihood to recommend the healthcare
      provider.

PMID- 20155555
TI  - Lasalocid awareness and sampling in Scotland.
AB  - Lasalocid is an ionophore antibiotic extensively used as a coccidiostat in
      poultry production. Lasalocid should not be fed to egg-laying hens as it
      accumulates in the eggs, and residues have often been found in eggs. Other
      ionophores are toxic to humans, but the exact level of lasalocid toxicity to
      humans has not been established. Approximately 250 egg samples were analysed for
      lasalocid each year from the 10 billion eggs consumed annually in the UK. A
      census of the 32 Scottish Local Authority Environmental Health Departments
      assessed awareness of lasalocid residues in eggs, and the results indicated that
      awareness of lasalocid was very low and no local authorities tested for
      lasalocid. The example of lasalocid revealed weaknesses in the current sampling
      regime surrounding foods of animal origin. Conclusions are drawn that central
      government should raise awareness within local authorities and provide financial
      support on local authority sampling to achieve proper representation.

PMID- 20155557
TI  - Episodic memory and organizational strategy in free recall in unipolar
      depression: the role of cognitive support and executive functions.
AB  - Executive functioning and memory impairment have been demonstrated in adults with
      depression. Executive functions and memory are related, mainly when the memory
      tasks require controlled processes (attentional resource demanding processes)-
      that is, when a low cognitive support (external aid) is provided. A cross
      sectional study was carried out on 45 participants: 21 with depression, and 24
      healthy controls matched for age, verbal ability, education level, and anxiety
      score. Cognitive support was manipulated by providing a categorized word list at
      encoding, presented either clustered (high cognitive support) or randomized (low
      cognitive support) to both depressed and healthy adults. The number of words
      recalled was calculated, and an index of clustering was computed to assess
      organizational strategies. Participants were also administered cognitive tests
      (executive functions, cognitive speed, and categorical fluency) to explore the
      mediators of organizational strategies. Depressed participants had greater
      difficulty recalling and organizing the words, but the differences between the
      two groups were reduced for both measures when high cognitive support was
      provided at encoding. Healthy adults performed better on all cognitive tests.
      Statistical analyses revealed that in the depressed group, executive functions
      were the only variable associated with clustering and only when low cognitive
      support was provided. These findings support the view that the decrement in
      executive function due to depression may lead to impairment in organization when
      this mnemonic strategy has to be self-initiated.

PMID- 20155558
TI  - Regional differences in relationships between apparent white matter integrity,
      cognition and mood in patients with ischemic stroke.
AB  - White matter changes are one potential etiology of behavioral changes in
      cerebrovascular disease. Whole brain diffusion tensor imaging-fractional
      anisotropy (DTI-FA) as a measure of apparent white matter integrity is related to
      cognitive function in cerebrovascular disease. However, white matter changes are
      not uniform, nor are their effects. We examine the relationship between regional
      differences in DTI-FA and cognition and mood in an ischemic-stroke sample.
      Participants were 108 patients, 3-6 months post stroke. Working memory, basic
      attention, recall, language, visuo-spatial, psychomotor, and encoding skills, and
      mood were assessed via neuropsychological evaluation. DTI scans were performed on
      a 1.5 T GE magnetic resonance imaging (MRI) system. Fractional anisotropy (FA)
      was calculated for frontal, temporal, occipital, and parietal regions using
      automated masks. Frontal and parietal FAs were more strongly and consistently
      related to cognitive and mood scores than were FA values from whole brain or
      temporal or occipital regions. This research contributes to our understanding of
      the etiology of cognitive and mood deficits in cerebrovascular disease.

PMID- 20155559
TI  - Nanoparticle usage and protection measures in the manufacturing industry--a
      representative survey.
AB  - Addressing the risks of nanoparticles requires knowledge about release into the
      environment and occupational exposure. However, such information currently is not
      systematically collected; therefore, this risk assessment lacks quantitative
      data. The goal was to evaluate the current level of nanoparticle usage in Swiss
      industry as well as health, safety, and environmental measures, and the number of
      potentially exposed workers. A representative, stratified mail survey was
      conducted among 1626 clients of the Swiss National Accident Insurance Fund
      (SUVA), which insures 80,000 manufacturing firms, representing 84% of all Swiss
      manufacturing companies (947 companies answered the survey for a 58.3% response
      rate). The extrapolation to all Swiss manufacturing companies results in 1309
      workers (95% confidence interval [CI]: 1073 to 1545) potentially exposed to
      nanoparticles in 586 companies (95% CI: 145 to 1027). This corresponds to 0.08%
      of workers (95% CI: 0.06% to 0.09%) and to 0.6% of companies (95% CI: 0.2% to
      1.1%). The industrial chemistry sector showed the highest percentage of companies
      using nanoparticles (21.2%). Other important sectors also reported nanoparticles.
      Personal protection equipment was the predominant protection strategy. Only a few
      applied specific environmental protection measures. This is the first nationwide
      representative study on nanoparticle use in the manufacturing sector. The
      information gained can be used for quantitative risk assessment. It can also help
      policymakers design strategies to support companies developing a safer use of
      nanomaterial. Noting the current low use of nanoparticles, there is still time to
      proactively introduce protective methods. If the predicted "nano-revolution"
      comes true, now is the time to take action.

PMID- 20155560
TI  - The relevance of the Rorschach and patient-examiner relationship in treatment
      planning and outcome assessment.
AB  - In this era of evidence-based mental health care, traditional forms of depth
      oriented psychotherapy and psychological assessment have been marginalized in
      graduate training in clinical psychology. As a counterpoint, this article
      presents the evaluation and treatment of an adolescent client, along with an
      outcome assessment, and illustrates ways that aspects of traditional
      psychological testing, including the Rorschach (Exner, 1986) and the patient
      examiner relationship, can enhance psychodiagnosis and treatment planning.
      Additionally, this case illustrates ways that test data can illuminate the
      concept of underlying disturbance and its utility in diagnostic formulation,
      treatment planning, and outcome assessment.

PMID- 20155561
TI  - A scale to measure nonattachment: a Buddhist complement to Western research on
      attachment and adaptive functioning.
AB  - The Buddhist notion of "nonattachment" (release from mental fixations) is related
      to but distinguishable from the Western construct of attachment. Secure (or
      insecure) attachment is based on internal working models related to security (or
      insecurity), whereas nonattachment is based on insight into the constructed and
      impermanent nature of mental representations. Based on historical and
      contemporary Buddhist scholarship, we designed the Nonattachment Scale and
      evaluated its psychometric properties in various samples. We also present
      evidence consistent with Buddhist theory that nonattachment is psychologically
      and socially adaptive, and we offer directions for further research on
      nonattachment.

PMID- 20155562
TI  - Assessment of alexithymia with the Rorschach Comprehensive System: the Rorschach
      Alexithymia Scale (RAS).
AB  - In this study, we developed the Rorschach Alexithymia Scale (RAS) to be used with
      protocols scored with the Comprehensive System (CS; Exner, 1993). A total of 92
      patients with medical disease and 127 psychiatric outpatients were administered
      the Rorschach and the 20-item Toronto Alexithymia Scale (Bagby, Parker, & Taylor,
      1994a, 1994b). We used a systematic approach, including cross-validation, to
      reduce a pool of 27 CS codes issued from an earlier investigation (Porcelli &
      Meyer, 2002) to 3 variables: Form%, CDI, and Pop. The RAS showed excellent
      diagnostic accuracy (hit rate of 92%, sensitivity of 88%, specificity of 94%, and
      area under the curve of .96). We suggest that the RAS can be used as a reliable
      integrative tool in a multimethod assessment approach to measuring alexithymia.

PMID- 20155563
TI  - The role of defense mechanisms in borderline and antisocial personalities.
AB  - We examined whether borderline personality disorder (BPD) and antisocial
      personality disorder (APD) could be differentiated based on defense mechanisms as
      measured by observer (Defense-Q; MacGregor, Olson, Presniak, & Davidson, 2008)
      and self-report (Defense Style Questionnaire; Andrews, Singh, & Bond, 1993)
      measures. We conducted 2 studies whereby nonclinical participants were divided
      into borderline and antisocial groups based on scores from the Personality
      Assessment Inventory (Morey, 1991). Multivariate analysis of variance results
      revealed significant overall group differences in defense use. Univariate
      analyses further showed group differences on several individual defenses (e.g.,
      acting out, denial, and turning against self). Together, the findings suggest
      that in BPD, the defenses may emphasize interpersonal dependency and a tendency
      to direct aggression toward the self; whereas in APD, the defenses may emphasize
      egocentricity, interpersonal exploitation, and a tendency to direct aggression
      toward others. Overall, this study demonstrates important differences in defense
      use between borderline and antisocial personality groups across both observer and
      self-report measures.

PMID- 20155564
TI  - Measuring empathy in couples: validity and reliability of the Interpersonal
      Reactivity Index for couples.
AB  - This article includes three studies aimed at adapting the Interpersonal
      Reactivity Index (Davis, 1980), a measure of general cognitive and emotional
      empathy, to assess empathy expressed within a romantic relationship. We examined
      the factorial structure of the Interpersonal Reactivity Index for Couples (IRIC).
      Results supported the use of the 2-factor measure (Dyadic Perspective Taking and
      Dyadic Empathic Concern) in 3 independent samples (individuals in heterosexual
      relationships, individuals in same-sex relationships, and partners of
      heterosexual couples). The IRIC also demonstrated good convergent, discriminant,
      concurrent, predictive, and incremental validity as well as adequate internal
      consistency and stability over 18 months.

PMID- 20155565
TI  - Differentiating adaptive and maladaptive perfectionism on the MMPI-2 and MIPS
      revised.
AB  - Although conceptualizations of perfectionism have emphasized adaptive as well as
      maladaptive expressions of the construct, how these different dimensions or types
      of perfectionists might be reflected in comprehensive personality assessment
      instruments is unknown. An initial sample of 267 university students completed
      the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom,
      Graham, Tellegen, & Kaemmer, 2001), Millon Index of Personality Styles Revised
      (MIPS-R; Millon, 2004), and Almost Perfect Scale-Revised (Slaney, Mobley, Trippi,
      Ashby, & Johnson, 1996). Analyses indicated that dimensions and types of
      perfectionism were associated, in expected directions, with select scores on the
      MMPI-2 and MIPS-R.

PMID- 20155566
TI  - Psychometric characteristics of a public-domain self-report measure of vocational
      interests: the Oregon Vocational Interest Scales.
AB  - We investigated the psychometric properties of the Oregon Vocational Interest
      Scales (ORVIS), a brief public-domain alternative to commercial inventories, in a
      large community sample and in a college sample. In both samples, we examined the
      factor structure, scale intercorrelations, and personality correlates of the
      ORVIS, and in the community sample, we also examined the correlations of the
      ORVIS scales with cognitive abilities and with the scales of a longer,
      proprietary interest survey. In both samples, all 8 scales-Leadership,
      Organization, Altruism, Creativity, Analysis, Producing, Adventuring, and
      Erudition-showed wide variation in scores, high internal-consistency
      reliabilities, and a pattern of high convergent and low discriminant correlations
      with the scales of the proprietary interest survey. Overall, the results support
      the construct validity of the scales, which are recommended for use in research
      on vocational interests and other individual differences.

PMID- 20155567
TI  - The Observer Alexithymia Scale: a reliable and valid alternative for alexithymia
      measurement?
AB  - In this study, we evaluated the reliability and validity of the Dutch version of
      the Observer Alexithymia Scale (OAS; Haviland, Warren, & Riggs, 2000) while
      addressing shortcomings of earlier research. Internal consistency and test-retest
      reliability were found to be adequate, whereas interrater reliability was
      insufficient. The original five-factor model (Distant, Uninsightful, Somatizing,
      Humorless, Rigid) with item parcels showed excellent fit, indicating adequate
      translation. Alternative models were tested to overcome problems with the parcel
      method, and all showed poor fit. OAS total scores correlated .23 with the 20-item
      Toronto Alexithymia Scale (Bagby, Parker, & Taylor, 1994; Bagby, Taylor, &
      Parker, 1994) and .50 with the Toronto Structured Interview for Alexithymia
      (Bagby, Taylor, Parker, & Dickens, 2006). These problematic results on validity
      compromise the use of the OAS as an alexithymia measure.

PMID- 20155568
TI  - Symbolic use of size and color in freehand drawing of the tree: myth or reality?
AB  - In this study, we tested whether children and young adults varied the size and
      color of their tree drawings based on hypotheses related to the emotional
      characterization of the drawn topic. We asked a sample of 80 5- to 11-year-old
      children and adults to draw a tree (baseline drawing) and then a happy versus sad
      tree from their imagination. Results indicate that size, but not color, is used
      to express emotion under free drawing conditions. We discuss implications for
      clinical psychologists and practitioners interpreting drawings of the tree.

PMID- 20155569
TI  - The influence of Cardan rotation sequence on angular orientation data for the
      lower limb in the soccer kick.
AB  - The influence of the Cardan rotation sequence on the orientation angles for
      joints is well known but has not been explored for dynamic sports movements. The
      purpose of this study is to establish the influence of Cardan rotation sequence
      on the orientation angles of the ankle, knee, and hip of the support leg and
      pelvis during dynamic sports movements, typified by a maximal instep kick in
      soccer. We found that: (a) the X (flexion/extension) axis rotations provide data
      that are robust for any sequence used other than the YXZ sequence, although the Y
      (abduction/adduction) and Z (internal/external) axes rotations are variable in
      both shape and offset magnitude; (b) the preferred rotation sequence is either
      XYZ or XZY for dynamic sports movements, although for the soccer kick the XYZ
      rotation sequence has been widely used and so this is recommended as a standard;
      and (c) most uncertainties exist in the Y and Z axes and are most apparent at the
      beginning of the movement. Where uncertainty exists in identifying Y and Z axes
      orientations, the integrated angular velocity may be considered as an alternative
      to determine the relative changes in segment orientation.

PMID- 20155570
TI  - Putts that get missed on the right: investigating lateralized attentional biases
      and the nature of putting errors in golf.
AB  - Although the effects of lateral biases in visual attention ("pseudoneglect") have
      been examined in real-world settings, this phenomenon has yet to be considered
      within the realm of sporting performance. In the present study, we investigated
      the effects of pseudoneglect on putting errors in golf. Novice golfers (n = 30)
      performed 90 putting trials followed by a series of pseudoneglect tasks:
      requiring participants to bisect lines manually and with a biomechanical
      bisection tool. All pseudoneglect measures were performed with both the left and
      right hands. Results demonstrated a leftward bias for all the pseudoneglect
      tasks, and a rightward bias for putting error. Moreover, the results revealed
      that individuals who bisected lines to the left on the Bisection Tool (the
      typical class of pseudoneglect error for humans) with the left hand (the hand
      that typically produces the greatest pseudoneglect bias) displayed significantly
      smaller rightward putting errors. Moreover, these individuals also holed more
      putts. No other pseudoneglect tasks were shown to impact on putting performance.
      Our findings suggest that lateralized attentional biases have a significant
      effect on sport performance; they appear to influence a wide range of precision
      based sports (e.g. shooting, archery). Findings are also discussed in terms of
      the processes that are likely to be involved in this effect.

PMID- 20155571
TI  - Maximal and submaximal physiological responses to adaptation to deep water
      running.
AB  - The aim of the study was to compare physiological responses between runners
      adapted and not adapted to deep water running at maximal intensity and the
      intensity equivalent to the ventilatory threshold. Seventeen runners, either
      adapted (n = 10) or not adapted (n = 7) to deep water running, participated in
      the study. Participants in both groups undertook a maximal treadmill running and
      deep water running graded exercise test in which cardiorespiratory variables were
      measured. Interactions between adaptation (adapted vs. non-adapted) and condition
      (treadmill running vs. deep water running) were analysed. The main effects of
      adaptation and condition were also analysed in isolation. Runners adapted to deep
      water running experienced less of a reduction in maximum oxygen consumption
      (VO2max) in deep water running compared with treadmill running than runners not
      adapted to deep water running. Maximal oxygen consumption, maximal heart rate,
      maximal ventilation, VO2max at the ventilatory threshold, heart rate at the
      ventilatory threshold, and ventilation at the ventilatory threshold were
      significantly higher during treadmill than deep water running. Therefore, we
      conclude that adaptation to deep water running reduces the difference in VO2max
      between the two modalities, possibly due to an increase in muscle recruitment.
      The results of this study support previous findings of a lower maximal and
      submaximal physiological response on deep water running for most of the measured
      parameters.

PMID- 20155572
TI  - Prospective memory in healthy Chinese people: the latent structure of the
      Comprehensive Assessment of Prospective Memory Questionnaire.
AB  - This study aimed to examine the latent structure of the Chinese version of the
      Comprehensive Assessment of Prospective Memory (CAPM) using confirmatory factor
      analysis. A total of 264 healthy Chinese participants (118 men and 146 women)
      took part in the study and their ages ranged from 17 to 90 years. There was no
      gender effect upon the frequency of prospective memory (PM) forgetting but age
      and education were found to be correlated significantly with these frequencies in
      the current sample. Results of the study also showed that the model with the best
      fit had a tripartite structure which consisted of a general memory factor (with
      all items loading on it) plus a basic activities of daily living as well as an
      instrumental activities of daily living factor. Furthermore, this tripartite
      model was robust across subgroups with respect to gender, education, and age.
      These findings provide support for the construct validity of the original CAPM
      and demonstrate its utility in another culture.

PMID- 20155573
TI  - Speaking in ellipses: the effect of a compensatory style of speech on functional
      communication in chronic agrammatism.
AB  - This study investigated whether a Dutch and adapted version of Reduced Syntax
      Therapy (REST) could stimulate and automatise the production of ellipses in Dutch
      speaking, chronically agrammatic speakers (N = 12). Ellipses are syntactic frames
      in which slots for grammatical morphology tend to be lacking (e.g., everybody
      inside). When elliptical style is applied on a regular basis, the linguistic
      impairment is circumvented, at least for the greater part. We therefore
      hypothesised that REST increases participants' functional communication skills
      (i.e., communicative efficacy and efficiency). This is of relevance because not
      all chronically agrammatic speakers become skilled at employing ellipses
      independently. The results of the present study suggested that when elliptical
      style is applied regularly, chronically agrammatic speakers get their message
      across more efficiently when compared to error-strewn production of sentential
      style.

PMID- 20155574
TI  - Normative data for composite scores for children and adults derived from the Rey
      Auditory Verbal Learning Test.
AB  - Norms on seven composite scores derived from the Rey Auditory Verbal Learning
      Test (AVLT) are reported here. These scores reflect a variety of verbal memory
      processes: learning, interference, retention over time, and retrieval efficiency.
      The norms are based on 943 children ranging in age from 8 to 17 years, divided
      into 10 age cohorts, and 528 adults, ranging in age from 21 to 91 years, divided
      into 6 age cohorts. Overall, the learning measures were the most sensitive to
      age. The most significant changes in memory as measured with these composite
      scores took place in the very young and very old age groups. These changes may be
      attributable to frontal lobe maturation in youth and deterioration in old age.
      Female participants show superiority over male participants on various verbal
      memory measures. These norms on the composite scores are primarily expected to
      serve the clinician in the process of memory assessment by supplementing the
      existing norms on individual trials of the Rey AVLT.

PMID- 20155575
TI  - Negative numbers in simple arithmetic.
AB  - Are negative numbers processed differently from positive numbers in arithmetic
      problems? In two experiments, adults (N = 66) solved standard addition and
      subtraction problems such as 3 + 4 and 7 - 4 and recasted versions that included
      explicit negative signs-that is, 3 - (-4), 7 + (-4), and (-4) + 7. Solution times
      on the recasted problems were slower than those on standard problems, but the
      effect was much larger for addition than subtraction. The negative sign may prime
      subtraction in both kinds of recasted problem. Problem size effects were the same
      or smaller in recasted than in standard problems, suggesting that the recasted
      formats did not interfere with mental calculation. These results suggest that the
      underlying conceptual structure of the problem (i.e., addition vs. subtraction)
      is more important for solution processes than the presence of negative numbers.

PMID- 20155576
TI  - Nanoparticles and potential human health implications: past and future
      directions. Preface.

PMID- 20155577
TI  - The physicochemistry and toxicology of CFA particles.
AB  - The term "technogenic particles" is used to describe airborne particulate matter
      (PM) produced during industrial processes. The most common of these is "fly ash"
      produced during combustion of solid and liquid fossil fuels. Coal fly ash is
      derived from the mineral and metal contaminants within coal in which particles
      (1) are distinctly spherical in shape, (2) are composed of 60-90% glass, and (3)
      often contain a range of contaminant metals. In addition, particles may contain
      recrystallized minerals, mainly quartz, mullite, and hematite; both quartz and
      mullite are recognized respiratory hazards. Fly ash particles from both UK and
      Chinese coal-burning power stations were characterized by field emission-scanning
      electron microscopy (morphology and size), x-ray diffraction (crystallinity and
      minerals), and inductively coupled plasma-mass spectroscopy (elemental
      composition). PM(10) samples were separated from bulk fly ash by a dry dust
      separator system. The plasmid scission assay (PSA) was used to measure damage
      produced by fly ash to plasmid bacteriophage PhiX174 RF DNA. The supercoiled DNA
      was either damaged or severely damaged by reactive oxygen species (ROS) generated
      by the fly ash at different concentrations. Geochemical analyses confirmed that
      the fly ash particles are predominantly glass, with a minor component of the
      minerals quartz, hematite, and mullite. Fly ash particles also contained a range
      of metals contaminants; however, these were mostly bound into the glass with only
      a small proportion potentially bioaccessible. PSA data showed that fly ash
      exhibited significant oxidative capacity when compared to negative control (MB
      H(2)O), indicating that ROS are likely to be the driving force underlying fly ash
      bioreactivity.

PMID- 20155578
TI  - Airborne particles in Swansea, UK: their collection and characterization.
AB  - Urban air particulate matter (PM) has previously been associated with a variety
      of adverse health effects. It is now believed that the smallest particles,
      ultrafine or nanoparticles, are linked to the greatest health effects. The
      physicochemistry of these particles is likely to provide information regarding
      their toxicity. Therefore, the aim of this study was to further the understanding
      of the heterogeneous and changing particle concentrations in urban air, in
      conjunction with gaining an understanding of the physicochemistry of the
      particles. A Dekati electrical low-pressure impactor was used to collect the
      particles and real-time data in a busy traffic corridor in Swansea, Wales, over a
      period of 10 nonconsecutive weeks. Particle concentrations in the street canyon
      were analyzed and particle physicochemistries investigated using a variety of
      techniques. Particle number concentrations were found to vary both diurnally and
      from day to day in the traffic corridor. Of all particles, the nano to fine size
      fraction was consistently identified in the highest concentrations (maximum:
      140,000 particles cm(-3)). Particle physicochemistry was found to vary as a
      function of size, with larger particles exhibiting a greater variety of
      morphologies (and consequently particle types) and associated metals.

PMID- 20155579
TI  - New detoxification processes for asbestos fibers in the environment.
AB  - Airborne asbestos fibers are associated with many serious detrimental effects on
      human health, while the hazard posed by waterborne fibers remains an object of
      debate. In adopting a precautionary principle, asbestos content in water needs to
      be kept as low as possible and polluting waters with asbestos should be avoided.
      Turci et al. (2008) recently reported a method for the decontamination of
      asbestos-polluted waters or landfill leachates from chrysotile that combines
      power ultrasound (US) with oxalic acid (Ox), an acidic chelating molecule. In the
      previous study, the occurrence of antigorite, a polymorph of serpentine, the
      mineral group encompassing chrysotile asbestos, acted as a confounding factor for
      complete removal of chrysotile from water. The effects of US + Ox on pure
      chrysotile asbestos from Val Malenco, Italian Central Alps, were examined in this
      investigation. In the absence of mineral contaminants, a more rapid removal of
      pure chrysotile from water was undertaken with respect to the previous specimen.
      After only 12 h of combined US + Ox acid treatment, imaging (SEM) of mineral
      debris indicated complete loss of fibrous habit. In addition, crystallography and
      vibrational features of chrysotile were not detectable (x-ray powder diffraction
      [XRPD] and micro-Raman spectroscopy) and elemental analysis showed a low Mg/Si
      ratio, i.e., the loss of the brucitic layer in chrysotile (x-ray fluorescence,
      XRF). Some nanometric rod-shaped debris, observed in the previous study and
      tentatively recognized as serpentine antigorite, was now found to be made of
      amorphous silica, which is relatively safe and noncarcinogenic to humans,
      providing further assurance regarding the safety of treated product. Thus, data
      indicated the proposed method was effective in detoxifying waterborne chrysotile
      asbestos fibers.

PMID- 20155580
TI  - Single- and multi-wall carbon nanotubes versus asbestos: are the carbon nanotubes
      a new health risk to humans?
AB  - Carbon nanotubes (CNT), since their discovery, have become one of the most
      promising nanomaterials in many industrial and biomedical applications. Due to
      their unique physicochemical properties, interest is growing in the manufacture
      of CNT-based products and their subsequent marketing. Since their discovery, the
      prospect of possible undesirable human health effects has been a focus of many
      scientific studies. Although CNT possess unique physical properties that include
      (1) nanoscale diameter, (2) a wide length distribution ranging from tens of
      nanometers to several micrometers, and (3) high aspect ratio, the fibrous-like
      shape and durability suggest that their toxic properties may be analogous to
      those observed with other fibrous particles, such as asbestos. The present study
      provides a summary of published findings on CNT bioactivity, such as the
      potential of CNT, especially of multi-wall carbon nanotubes (MWCNT), to activate
      signaling pathways modulating transcription factor activity, induce apoptosis,
      induce DNA damage, and initiate biological responses. Assessment of risks to
      human health and adoption of appropriate exposure controls is critical for the
      safe and successful introduction of CNT -based products for future applications.

PMID- 20155581
TI  - Pulmonary inflammation after intraperitoneal administration of ultrafine titanium
      dioxide (TiO2) at rest or in lungs primed with lipopolysaccharide.
AB  - Nanoparticles are widely used in nanomedicines, including for targeted delivery
      of pharmacological, therapeutic, and diagnostic agents. Since nanoparticles might
      translocate across cellular barriers from the circulation into targeted organs,
      it is important to obtain information concerning the pathophysiologic effects of
      these particles through systemic migration. In the present study, acute pulmonary
      responses were examined after intraperitoneal (ip) administration of ultrafine
      titanium dioxide (TiO(2), 40 mg/kg) in mice at rest or in lungs primed with
      lipopolysaccharide (LPS, ip, 5 mg/kg). Ultrafine TiO(2) exposure increased
      neutrophil influx, protein levels in bronchoalveolar lavage (BAL) fluid, and
      reactive oxygen species (ROS) activity of BAL cells 4 h after exposure.
      Concomitantly, the levels of proinflammatory mediators, such as tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta, and macrophage inflammatory protein
      (MIP)-2 in BAL fluid and mRNA expression of TNF-alpha and IL-1beta in lung tissue
      were elevated post ultrafine TiO(2) exposure. Ultrafine TiO(2) exposure resulted
      in significant activation of inflammatory signaling molecules, such as c-Src and
      p38 MAP kinase, in lung tissue and alveolar macrophages, and the nuclear factor
      (NF)-kappaB pathway in pulmonary tissue. Furthermore, ultrafine TiO(2) additively
      enhanced these inflammatory parameters and this signaling pathway in lungs primed
      with lipopolysaccharide (LPS). Contrary to this trend, a synergistic effect was
      found for TNF-alpha at the level of protein and mRNA expression. These results
      suggest that ultrafine TiO(2) (P25) induces acute lung inflammation after ip
      administration, and exhibits additive or synergistic effects with LPS, at least
      partly, via activation of oxidant-dependent inflammatory signaling and the NF
      kappaB pathway, leading to increased production of proinflammatory mediators.

PMID- 20155582
TI  - Direct fibrogenic effects of dispersed single-walled carbon nanotubes on human
      lung fibroblasts.
AB  - Nanomaterials, including single-walled carbon nanotubes (SWCNT), are being
      developed for a variety of commercial products. However, adverse health effects
      attributed to these new materials are not well understood. Recent reports showed
      that exposure of mice to dispersed SWCNT (DSWCNT) produced a rapid and
      progressive interstitial lung fibrosis without persistent inflammation. To
      understand the mechanism underlying this unusual fibrogenicity of DSWCNT, the
      present investigation focused on the direct bioactivity of DSWCNT using a cell
      culture of lung fibroblasts that represent a major cell type resident in the lung
      interstitium and responsible for the production of collagen matrix. At
      concentrations relevant to those used in vivo, in vitro exposure of lung
      fibroblasts to DSWCNT stimulated cell proliferation and induced collagen
      production without producing cell damage. One of the major matrix
      metalloproteinases (MMP), MMP-9, which is known to be involved in lung fibrosis,
      was also elevated by DSWCNT treatment both in vitro and in vivo. Taken together,
      these results suggest that direct stimulation of fibroblasts by DSWCNT
      translocated into the interstitium may play a significant role in DSWCNT-induced
      lung fibrosis. Our data also suggest that the dispersion status and/or size of
      the SWCNT structures is a critical factor in determining nanoparticle
      fibrogenicity and that MMP-9 may be involved in the fibrogenic process. The
      results obtained may aid in the development of in vitro models for rapid
      screening of the potential fibrogenicity of carbon nanotubes, which are lacking
      and urgently needed.

PMID- 20155584
TI  - Exhaled nitric oxide levels and lung function changes of underground coal miners
      in Newcastle, Australia.
AB  - The possibility of exhaled nitric oxide (eNO) in combination with lung function
      as a marker of airway inflammation produced by coal mining exposure was
      determined presuming that workers exposed to airborne hazards would possess
      different concentrations of eNO and decreased lung function indices, relative to
      control subjects recruited from the same area. The effect of smoking was also
      considered. A study (exposed) group comprising 186 male subjects (aged 19-58 yr)
      was recruited from Newcastle coal mining companies with 86 male subjects (aged 20
      64 yr) from the same area, but working outside of the coal mining location,
      serving as controls. The parameters examined were eNO, lung function, and
      variables derived from an interview-administered questionnaire survey. After
      adjustment for age, body weight, and smoking status, no significant differences
      between exposed coal mining workers and controls were found for various lung
      function parameters. However, the exposed group was shown to have significantly
      lower concentrations of eNO. In the exposed group, forced expiratory volume in 1
      s (FEV(1)), forced vital capacity (FVC), and FEV(1) (%) predicted were found to
      be significantly different between nonsmokers and smokers. The concentrations of
      eNO were not significantly different between smoking and nonsmokers within the
      exposed group. The consideration of nonsmokers alone showed that eNO was
      significantly lower in the exposed group compared to the control group. The
      consideration of smokers alone found that eNO was significantly lower in exposed
      subjects. In the exposed group, no significant association was detected between
      eNO levels and underground work duration but a significant negative association
      was shown between eNO and age. Data suggest that exposure to airborne hazards in
      coal mining is not significantly associated with lung function changes but is
      correlated with decreased eNO concentrations in exposed workers. While
      underground work duration was not found to be significantly associated with eNO
      concentrations in coal mining workers in this study, the potential for using eNO
      as a monitoring marker still exists and further studies are needed to establish
      its importance.

PMID- 20155583
TI  - Utilization of gene profiling and proteomics to determine mineral pathogenicity
      in a human mesothelial cell line (LP9/TERT-1).
AB  - Identifying and understanding the early molecular events that underscore mineral
      pathogenicity using in vitro screening tests is imperative, especially given the
      large number of synthetic and natural fibers and particles being introduced into
      the environment. The purpose of the work described here was to examine the
      ability of gene profiling (Affymetrix microarrays) to predict the pathogenicity
      of various materials in a human mesothelial cell line (LP9/TERT-1) exposed to
      equal surface area concentrations (15 x 10(6) or 75 x 10(6) microm(2)/cm(2)) of
      crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO(2)), or glass
      beads for 8 or 24 h. Since crocidolite asbestos caused the greatest number of
      alterations in gene expression, multiplex analysis (Bio-Plex) of proteins
      released from LP9/TERT-1 cells exposed to crocidolite asbestos was also assessed
      to reveal if this approach might also be explored in future assays comparing
      various mineral types. To verify that LP9/TERT-1 cells were more sensitive than
      other cell types to asbestos, human ovarian epithelial cells (IOSE) were also
      utilized in microarray studies. Upon assessing changes in gene expression via
      microarrays, principal component analysis (PCA) of these data was used to
      identify patterns of differential gene expression. PCA of microarray data
      confirmed that LP9/TERT-1 cells were more responsive than IOSE cells to
      crocidolite asbestos or nonfibrous talc, and that crocidolite asbestos elicited
      greater responses in both cell types when compared to nonfibrous talc, TiO(2), or
      glass beads. Bio-Plex analysis demonstrated that asbestos caused an increase in
      interleukin-13 (IL-13), basic fibroblast growth factor (bFGF), granulocyte colony
      stimulating factor (G-CSF), and vascular endothelial growth factor (VEGF). These
      responses were generally dose-dependent (bFGF and G-CSF only) and tumor necrosis
      factor (TNF)-alpha independent (except for G-CSF). Thus, microarray and Bio-Plex
      analyses are valuable in determining early molecular responses to
      fibers/particles and may directly contribute to understanding the etiology of
      diseases caused by them. The number and magnitude of changes in gene expression
      or "profiles" of secreted proteins may serve as valuable metrics for determining
      the potential pathogenicity of various mineral types. Hence, alterations in gene
      expression and cytokine/chemokine changes induced by crocidolite asbestos in
      LP9/TERT-1 cells may be indicative of its increased potential to cause
      mesothelioma in comparison to the other nonfibrous materials examined.

PMID- 20155585
TI  - Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and
      chemical/biological response metrics.
AB  - Engineered nanoparticles (NP) are being developed and incorporated in a number of
      commercial products, raising the potential of human exposure during manufacture,
      use, and disposal. Although data concerning the potential toxicity of some NP
      have been reported, validated simple assays are lacking for predicting their in
      vivo toxicity. The aim of this study was to evaluate new response metrics based
      on chemical and biological activity of NP for screening assays that can be used
      to predict NP toxicity in vivo. Two cell-free and two cell-based assays were
      evaluated for their power in predicting in vivo toxicity of eight distinct
      particle types with widely differing physicochemical characteristics. The cell
      free systems comprised fluorescence- and electron spin resonance-based assays of
      oxidant activity. The cell-based systems also used electron spin resonance (ESR)
      as well as luciferase reporter activity to rank the different particle types in
      comparison to benchmark particles of low and high activity. In vivo experiments
      evaluated acute pulmonary inflammatory responses in rats. Endpoints in all assays
      were related to oxidative stress and responses were expressed per unit NP surface
      area to compare the results of different assays. Results indicated that NP are
      capable of producing reactive species, which in biological systems lead to
      oxidative stress. Copper NP had the greatest activity in all assays, while TiO(2)
      and gold NP generally were the least reactive. Differences in the ranking of NP
      activity among the assays were found when comparisons were based on measured
      responses. However, expressing the chemical (cell-free) and biological (cells; in
      vivo) activity per unit particle surface area showed that all in vitro assays
      correlated significantly with in vivo results, with the cellular assays
      correlating the best. Data from this study indicate that it is possible to
      predict acute in vivo inflammatory potential of NP with cell-free and cellular
      assays by using NP surface area-based dose and response metrics, but that a
      cellular component is required to achieve a higher degree of predictive power.

PMID- 20155586
TI  - President's Message.

PMID- 20155587
TI  - Alexithymia and pathological gambling.
AB  - The purpose of this study was to study the relationship between alexithymia and
      gambling in a community sample of pathological gamblers. Pathological, problem
      and non-problem gamblers were recruited from the community via advertisements and
      completed an assessment of their gambling behavior and the Toronto Alexithymia
      Scale. Alexithymia was higher among male pathological gamblers who identified
      slot machines, cards, and lotteries as their primary gambling problem. High
      alexithymics scored higher on Diagnostic and Statistical Manual symptoms related
      to poor self-regulation, communication, and problem-solving skills. Although a
      correlational study, the evidence suggests that further investigation of the
      clinical significance of alexithymia in individuals with severe gambling
      pathology is indicated.

PMID- 20155588
TI  - Pathological gambling and obsessive compulsive disorder among methadone
      maintenance treatment patients.
AB  - The aims of this study was to assess the prevalence of lifetime pathological
      gambling (pathological gambling) and current obsessive compulsive disorder among
      former heroin addicts currently in methadone maintenance treatment. A cross
      sectional study of 154 patients from a methadone maintenance treatment clinic
      affiliated of a tertiary-referral medical center was conducted. The South Oaks
      Gambling Screen and Yale-Brown Obsessive Compulsive Scale were used for
      measurement purposes. Lifetime pathological gambling was found in 45 (29.2%)
      patients (current pathological gambling was found in 10 [6.5%] patients).
      Clinical obsessive compulsive disorder (defined if scored as moderate to extreme)
      was found in 51.1% of patients in the pathological gambling groups and 39.4% of
      patients in the non-pathological gambling group, with higher obsessive scores in
      the pathological gambling group versus the non-pathological gambling group.
      Logistic regression (multivariate analyses) found pathological gambling in more
      males (odds ratio = 3.6, 95% confidence interval = 1.5-8.8), a high obsessive
      score (odds ratio = 1.07, 95% confidence interval = 0.1-1.1), and older age on
      admission (40 years and older) (odds ratio = 2.4, 95% confidence interval = 1.1
      5.0). Because only 10 (6.5%) patients were still currently gambling, more urgent
      intervention should be considered to the unexpected high rate of clinical
      obsessive-compulsive disorder (42.9%) in the sample, possibly because the clinic
      studied is of a higher severity than that accepted to the methadone maintenance
      treatment clinics in the community.

PMID- 20155589
TI  - Comparison of substance use and risky sexual behavior among a diverse sample of
      urban, HIV-positive men who have sex with men.
AB  - The purpose of this study was to examine substance use among a racially and
      ethnically diverse group of HIV-positive men who have sex with men (MSM) living
      in six U.S. cities, model associations between drug use and serodiscordant
      unprotected anal intercourse (SDUAI), and characterize users of the substances
      strongly associated with risky sexual behavior. Baseline questionnaire data from
      675 participants of the Positive Connections intervention trial were analyzed.
      Overall, substance use was common; however, the highest percentage of stimulant
      (30%), methamphetamine (27%), and popper (i.e., amyl nitrite) (46%) use was
      reported among white MSM and crack/cocaine (38%) use was highest among African
      American MSM. Popper use versus non-use (odds ratio = 2.46; 95% confidence
      interval = 1.55-3.94) and condom self-efficacy (1 standard deviation (sd)
      increase on scale; odds ratio = .58; 95% confidence interval = .46-.73) were
      significantly associated with SDUAI after adjusting for key demographic and
      psychosocial factors. These results highlight the importance of addressing drug
      use in the context of sex for possible HIV transmission risk.

PMID- 20155590
TI  - Insomnia among methadone-maintained individuals: the feasibility of collecting
      home polysomnographic recordings.
AB  - Sleep disturbance among methadone-maintained patients is highly prevalent. A full
      understanding of sleep disturbance requires polysomnographic measures along with
      subjective sleep quality measures. The goal of this study was to describe the
      authors' experiences in performing at-home unattended polysomnography in this
      population. Participants had a Pittsburgh Sleep Quality Index score of six or
      higher, which indicates clinically significant insomnia, and 65% of eligible
      individuals agreed to enroll. Among 88 participants (53% female, 82% white, and a
      mean methadone dose of 105 mg/day), each undergoing two nights of home
      polysomnography, we initiated 165 of a maximum of 176 recordings. Overall, 81.7%
      of participants provided at least one night of "acceptable" polysomnographic data
      of at least 4 hours duration. Urine toxicology on polysomnographic nights
      demonstrated that benzodiazepine use was common. The authors conclude that
      unattended polysomnography is feasible in a population of individuals receiving
      methadone maintenance treatment. Polysomnography signal quality and overall study
      success rates were similar to those in non-substance using populations.

PMID- 20155591
TI  - Diversion of buprenorphine/naloxone coformulated tablets in a region with high
      prescribing prevalence.
AB  - The purpose of this article was to characterize practices of
      buprenorphine/naloxone (B/N) diversion in a region with a high prescribing
      prevalence. A cross-sectional, open-ended survey was administered to individuals
      entering opioid addiction treatment programs in two New England states. The
      authors obtained formative information about the knowledge, attitudes, beliefs,
      practices, and street economy of B/N diversion. The authors interviewed 51
      individuals, 49 of which were aware of B/N medication. Of that number, 100% had
      diverted B/N to modulate opiate withdrawal symptoms arising from attempted "self
      detoxification," insufficient funds to purchase preferred illicit opioids, or
      inability to find a preferred source of drugs. Thirty of 49 (61%) participants
      obtained the illicit drug from an individual holding a legitimate prescription
      for B/N. A high proportion of individuals in the study locations who sought
      treatment for opioid addiction self-reported the purchase and use of diverted
      B/N. The diversion of B/N may be minimized by modifying educational, treatment,
      monitoring, and dispensing practices.

PMID- 20155592
TI  - Non-medical use of prescription analgesics: a three-year national longitudinal
      study.
AB  - This secondary analysis of the National Epidemiologic Survey on Alcohol and
      Related Conditions (NESARC) data examined the non-medical use of prescription
      analgesics and determined its relationship to continued non-medical use and
      substance use disorders 3 years later. Prospective data were collected using the
      Alcohol Use Disorders and Associated Disabilities Interview Schedule: DSM-IV
      Version (AUDADIS-DSM-IV). A nationally representative sample (n = 34,653) of U.S.
      adults 18 years or older were interviewed at Wave 1 (2001-2002) and re
      interviewed at Wave 2 (2004-2005). Multivariate logistic regression analyses
      indicated younger age (18 to 24 years) and non-medical use at Wave 1 was
      associated with higher odds of a general substance or opioid use disorder at Wave
      2 (adjusted odds ratio = 3.42, 95% confidence interval = 1.45, 8.07); however,
      most respondents who engaged in non-medical use will cease using 3 years later
      although non-medical use is associated with higher prevalence of a future
      substance use disorder.

PMID- 20155593
TI  - Is self-reported "moderate" drinking in the cardiovascular benefit range
      associated with alcoholic behavior? A population based study.
AB  - This article aims at identifying a threshold number of drinks per day beyond
      which there is a high risk of developing alcoholic behavior that would enable
      physicians to more confidently support the use of alcohol for cardiovascular risk
      prevention. In a randomly selected, population-based sample of 2,042 adults 45
      years or older, we graded alcohol drinking behavior using the Self-Administered
      Alcoholism Screening Test, quantified alcohol amount by questionnaire, and
      assessed the prevalence of cardiovascular disease (coronary, peripheral, or
      cerebrovascular disease) by medical record review. Although optimal alcohol use
      (< or = 2 drinks/day) was associated with reduced odds of cardiovascular disease,
      43% of alcoholics and 82% of problem drinkers reported alcohol use in the optimal
      range as well. The association of alcohol use in the optimal range with alcohol
      related behavioral problems supports the reluctance in physicians from
      recommending alcohol use for cardiovascular benefit, not withstanding the
      underreporting of alcohol use by alcoholics.

PMID- 20155595
TI  - Substance abuse and dependence among low income African Americans: using data
      from the national survey on drug use & health to demystify assumptions.
AB  - The media has portrayed African Americans as drug users and criminals. The
      purpose of this study is to test the assumption that low-income African Americans
      use more alcohol, nicotine, marijuana, and illicit drugs than other racial groups
      using data from the 2005 National Survey on Drug Use and Health to compare drug
      abuse and dependence across low income racial groups (N = 20,172). Most
      respondents were white, female, and older than 26 years of age. The majority
      completed high school and reported annual family incomes between $10,000 and
      $19,000. Few participants reported receiving public assistance. Drug abuse and
      dependence rates varied across drug type and across race. Drug dependence and
      abuse were measured using the Nicotine Dependence Syndrome Scale and criteria
      from the Diagnostic and Statistical Manual of Mental Disorders. Hierarchical
      regression was conducted to examine the level of association between racial
      background and drug abuse and dependence after controlling for age and gender.
      Results reveal that the assumption of high drug and alcohol use and abuse rates
      among low-income African Americans should be, at best, reexamined. This study has
      significant implications for both policy and social work practice because it
      breaks down normalized and biased assumptions of low-income African American drug
      use.

PMID- 20155594
TI  - Baseline neurocognitive profiles differentiate abstainers and non-abstainers in a
      cocaine clinical trial.
AB  - Previous studies have shown that cocaine users have higher levels of impulsivity
      and impaired decision making; however, few have examined these factors as
      predictors of treatment success. We obtained baseline neurocognitive measures
      from 75 cocaine-dependent individuals participating in a 12-week clinical trial
      targeting impulsivity with behavioral therapies and pharmacotherapy. Participants
      treated with citalopram had higher cocaine abstinence rates compared to placebo
      treated participants. The aim of this secondary analysis study was to determine
      whether profiles of performance on neurocognitive measures administered at
      baseline discriminated among patients who achieved abstinence and those who did
      not. Participants completed the Immediate and Delayed Memory Task, Barratt
      Impulsiveness Scale-11, and Iowa Gambling Task. Profile analysis results showed
      different patterns of performance on these baseline measures as a function of
      outcome. Compared with non-abstinent participants, abstinent participants had
      higher scores on the Barratt Impulsiveness Scale-11 Non-Planning subscale and
      better performance on the Iowa Gambling Task. Profile differences for the two
      outcome groups did not vary as a function of treatment condition. Results suggest
      that cocaine-dependent patients entering treatment with higher impulsivity and
      less impaired decision-making abilities may respond favorably to targeted
      behavioral interventions. Neurocognitive profiles may be useful in understanding
      population heterogeneity and predicting differential outcomes in subgroups of
      cocaine abusers.

PMID- 20155596
TI  - What is diversion of supervised buprenorphine and how common is it?
AB  - This study aimed to identify the practices of community pharmacists regarding the
      provision of buprenorphine for opioid dependence and explore behaviors
      pharmacists considered indicative of buprenorphine diversion. A cross-sectional
      survey of 669 community pharmacists authorized to dispense buprenorphine or
      methadone was conducted in New South Wales and Victoria, Australia. There was
      wide variation between pharmacies in the level of supervision provided during
      supervised buprenorphine dosing and a lack of clarity between pharmacists
      regarding what behaviors are examples of buprenorphine diversion. Compared to New
      South Wales, a higher proportion of Victorian pharmacists detected 1 or more
      episodes of buprenorphine diversion in the past year (65% vs. 28%; p < .001) and
      in the past month (20% vs. 7%; p < .001). Detection of buprenorphine diversion
      was associated with the administration of crushed tablets (odds ratio = 2.77),
      broken tablets (odds ratio = 2.69), and having more buprenorphine clients (odds
      ratio = 1.24). Future research investigating the prevalence of buprenorphine
      diversion should include a clear definition of what behaviors constitute
      diversion.

PMID- 20155599
TI  - Mental health service utilization and drinking outcomes in a national population
      sample: are there racial/ethnic differences?
AB  - Racial and ethnic disparities in alcohol use and alcohol-related problems have
      been well-documented. Less information is available about possible disparities in
      outcomes related to mental health services utilization. The differential effect
      of mental health services use by race on drinking outcomes was examined. Wave 2
      of a national population sample of employed adults who reported having at least
      one alcoholic drink in the past year (N = 1,058) encompassed measures of the
      prevalence of mental health services use in response to stress, and alcohol
      related outcomes. Non-white participants who reported using any mental health
      services, four or more mental health visits in the past year, and eight or more
      mental health visits in the past year reported lower rates of problematic
      drinking behaviors, including frequency of drinking to intoxication, heavy
      episodic drinking, and modified Brief MAST scores, than whites who reported
      similar use of mental health services.

PMID- 20155600
TI  - The social consequences of binge drinking: a comparison of young adults in six
      European countries.
AB  - A considerable amount of survey information was available from general population
      surveys carried out in six countries between 2000 and 2005. These studies were
      conducted under the auspices of Gender, Alcohol and Culture: An International
      Study (GENACIS). A total of 1,446 adults between 18 and 23 years of age and 2,482
      adults between 24 and 32 years of age from the Czech Republic, Denmark, the Isle
      of Man, Spain, Sweden, and the United Kingdom responded to questions about their
      drinking habits and the social consequences directly resulting from their
      drinking. Survey methods varied from quota sampling with face-to-face
      interviewing in Spain and the United Kingdom to telephone surveys in Denmark and
      Sweden. Response rates varied from 50% to 72%. "Binge" or "heavy episodic"
      drinking was defined as a usual amount on one occasion of more than 8 UK "units"
      for men and more than 6 units for women. Consequences investigated comprised
      relationship, health and financial problems, being asked to cut down on drinking,
      and being involved in a fight. In Denmark and Sweden, the group aged 24 to 32
      years was less likely to be binge drinkers than the 18 to 23 year olds. In the
      other countries, there was little difference. There was also little difference
      between the age groups in frequency of drinking, but there were considerable
      variations in this respect between countries. People in the United Kingdom,
      Sweden, the Czech Republic, and Denmark were more likely to suffer at least one
      consequence than those in Spain and the Isle of Man. In Spain, there was little
      change between the age groups in this respect. Fights were most common in the
      United Kingdom. Being asked to cut down one's drinking was less common in Spain
      and Sweden than it was elsewhere. Findings are discussed in terms of the varied
      drinking cultures in the different countries.

PMID- 20155601
TI  - Comorbid mood, psychosis, and marijuana abuse disorders: a theoretical review.
AB  - There is a need to bridge the gap between the fields of addiction psychiatry and
      general psychiatry to effectively treat co-morbid substance abuse and psychiatric
      disorders. This alarming epidemic transcends communities and severely impacts
      healthcare worldwide, yielding poor treatment outcomes and prognoses for
      afflicted patients. Because substance abuse can exacerbate or trigger psychosis
      and mood disorders, it is important to keep these issues in the forefront when
      evaluating patients. To address some of the complications stemming from not
      enough interactions between various groups of practitioners, this review
      addresses the neurobehavioral effects of cannabis use and their impact on
      patients who suffer from psychotic or affective disorders. The hope is that this
      article will serve as a spring board for further discussions among practitioners
      who treat these patients. Greater interactions between caretakers are bound to
      impact the care of our patients in a very positive way.

PMID- 20155602
TI  - Lifetime substance misuse and 5-year incidence rates of emergent health problems
      among middle-aged adults.
AB  - Understanding the impact of prior substance misuse on emergent health problems is
      important to the implementation of effective preventive care. This study examined
      the 5-year incidence rates using a sample of middle-aged adult adoptees (N = 309,
      mean(age) = 44.32, standard deviation(age) = 7.28). Subjects reported on health
      problems at two waves of study. DSM-IV diagnoses of substance misuse were
      obtained using a semi-structured diagnostic interview. Finally, health services
      utilization and perceived health status were collected. Lifetime diagnoses of
      marijuana and other non-marijuana substance misuse significantly predicted new
      occurrences of cardiovascular and metabolic disease. Alcohol misuse predicted
      earlier onset of cardiovascular disease among men. Marijuana and other non
      marijuana drugs predicted earlier onset of cardiovascular disease for men and
      women. Finally, marijuana and other non-marijuana drugs predicted earlier onset
      of metabolic disease among men. Substance misuse did not predict health services
      utilization despite higher rates of disease. These findings emphasize the need to
      assess lifetime substance misuse when evaluating health risks associated with
      use.

PMID- 20155603
TI  - The "black box" of prescription drug diversion.
AB  - A variety of surveys and studies are examined in an effort to better understand
      the scope of prescription drug diversion and to determine whether there are
      consistent patterns of diversion among various populations of prescription drug
      abusers. Data are drawn from the RADARS System, the National Survey of Drug Use
      and Health, the Delaware School Survey, and a series of quantitative and
      qualitative studies conducted in Miami, Florida. The data suggest that the major
      sources of diversion include drug dealers, friends and relatives, smugglers, pain
      patients, and the elderly, but these vary by the population being targeted. In
      all of the studies examined, the use of the Internet as a source for prescription
      drugs is insignificant. Little is known about where drug dealers are obtaining
      their supplies, and as such, prescription drug diversion is a "black box"
      requiring concentrated, systematic study.

PMID- 20155604
TI  - Antidepressant-induced mania with concomitant mood stabilizer in patients with
      comorbid substance abuse and bipolar disorder.
AB  - Antidepressant use in the treatment of bipolar disorder is controversial due the
      risks of affective switching and cycle acceleration. Studies of non-comorbid
      samples suggest that the risk can be mitigated with the use of a concomitant mood
      stabilizer. However, the majority of patients with bipolar disorder will
      experience a comorbid substance use disorder and little is known about these
      individuals because they are typically excluded from clinical trials. Patients
      entering a substance abuse treatment program who had a history of bipolar
      disorder were interviewed to evaluate antidepressant-induced affective switching
      with and without concomitant mood stabilizer. Among 41 comorbid participants, the
      total lifetime antidepressant-induced switch rate was 76%. The switch rate was
      56% for patients taking a mood stabilizer and an antidepressant concomitantly.
      There was no difference between patients with bipolar I and bipolar II disorders.

PMID- 20155605
TI  - The power of the drug, nature of support, and their impact on homeless youth.
AB  - The purpose of this study was to explore homeless youths' perspectives on the
      power of drugs in their lives, the preferred type of drugs used, barriers to
      treatment, and strategies to prevent drug initiation and abuse. This was a
      descriptive, qualitative study using focus groups with a purposeful sample of 24
      drug-using homeless youth. The results provided insight into the lives of drug
      using homeless youth. The most commonly used drugs were marijuana and alcohol.
      Reported reasons for drug use were parental drug use, low self-esteem, and harsh
      living conditions on the streets. Barriers to treatment were pleasurable
      enjoyment of the drug, physical dependence, and non-empathetic mental health
      providers. Strategies to prevent initiation and abuse of drugs were creative
      activities, such as art, sports, and music, and disdain for parental/family drug
      use and abuse. Comparative research is needed on specific personal factors that
      cause initiation and deterrence of drugs use/abuse among homeless youth.

PMID- 20155606
TI  - Correlates of intimate partner violence among men and women in an inner city
      emergency department.
AB  - The current study surveyed medical or injured patients (men and women) in an
      inner city emergency department to examine the rates and correlates of intimate
      partner violence, including substance use patterns. Over a 2-year period,
      participants (n = 10,744) self-administered a computerized health survey during
      their emergency department visit that included screening items regarding past
      year history of intimate partner violence (including victimization and
      aggression). Overall, rates of any intimate partner violence involvement in past
      year were 8.7% (7.3% victimization and 4.4% aggression); however, women were more
      likely than men to report intimate partner violence. When examining participants'
      substance use patterns, participants who reported using both alcohol and cocaine
      were most likely to report intimate partner violence. Predictors of partner
      aggression and victimization were remarkably similar. This article provides
      unique data regarding correlates of past year intimate partner violence history
      among a comprehensive sample of male and female emergency department patients
      presenting for medical complaints or injury.

PMID- 20155607
TI  - Use of street methadone in italian heroin addicts presenting for opioid agonist
      treatment.
AB  - It is commonly assumed that people who are addicted to certain substances would
      abuse any substance. This position has never been supported by validly collected
      and analyzed research data. In this study, the authors examine the use of street
      methadone by heroin addicts seeking their first agonist opioid treatment in a
      clinical setting. Fifty-four heroin addicts who resorted to street methadone use
      were compared by socio-demographic, current clinical, and disease-related
      variables to 251 peers who do not use street methadone. Heroin addicts who resort
      to street methadone use are more likely to be females and to have a higher degree
      of education, are less likely to engage in polyabuse (use of more than three
      substances), are less severely ill, have been addicted for a shorter period of
      time, and have been seeking treatment sooner in the course of their disease.
      Also, they suffer from a wider range of psychopathological distress symptoms. In
      Italy, resorting to street methadone does not seem to be a surrogate form of
      heroin addiction, but rather represents means of harm reduction, with treatment
      seeking occurring shortly after its initiation. This should be accounted for when
      deciding on take-home policies and issues of potential methadone diversion.

PMID- 20155608
TI  - A trial to reduce hepatitis C seroincidence in drug users.
AB  - To test whether a four-session motivational intervention would reduce hepatitis C
      virus (HCV) seroincidence among injection and non-injection drug users compared
      to an assessment-only condition, we performed a randomized 24-month clinical
      trial. At baseline, 277 participants reported using heroin or cocaine at least
      three times weekly were HCV antibody negative, 65% were male and 46% were
      Caucasian and 39% reported having injected drugs. Of the 15 (5.4%) individuals
      who seroconverted, all reported injecting drugs either at baseline or during
      follow-up. Seroconversion rates did not differ significantly by treatment
      assignment (p =.79). The annual HCV incident rate was 8.20 (95% confidence
      interval [CI] = 4.76-14.13) for injectors and 0.74 (95% CI = 0.19-2.98) for non
      injectors per 100 person-years. Significantly fewer participants in the
      intervention group initiated injection drug use behaviors (p =.009). This
      intervention was no more effective at reducing HCV seroconversion than assessment
      alone but did decrease injection initiation.

PMID- 20155609
TI  - High dose versus moderate dose methadone maintenance: is there a better outcome?
AB  - Methadone dosing has been an issue of controversy among clinicians for a long
      time. Few recent studies reported that doses above 100 mg daily seem promising in
      better control of illicit opiate use for some patients, but more research is
      needed to support that notion. A retrospective chart review for patients
      maintained on methadone at Atlanta Veterans Affairs Medical Center was conducted.
      Patients were categorized into two groups: patients on a methadone dose of 60 to
      100 mg daily (n = 34) and patients on a methadone dose greater than 100 mg daily
      (n = 25). Those charts were compared for urine drug screens for opiates and
      cocaine (first four from admission and most recent four screens), retention or
      drop out from the program, and Addiction Severity Index (ASI) composite score at
      admission and most recent score. The results of the first and last four urine
      drug screens for opiates showed that the moderate dose group was positive 23% and
      17%, respectively. However, the high dose group was positive 14% and 8%,
      respectively. These results showed statistical significance (Chi-Square = 8.04,
      df = 3 and p =.03). ASI scores for drugs did not show statistically significant
      improvement for the moderate dose group (p =.19) but showed statistically
      significant improvement for the high dose group (p =.0002) when the result of the
      first and last ASI scores among each group were compared. The ASI scores for
      family problems showed statistically significant improvement for the moderate
      dose group (p =.03). High doses of methadone greater than 100 mg daily may
      provide a better outcome for illicit opiate use among some patients who would not
      respond to moderate doses.

PMID- 20155612
TI  - First International Congress on Nutrition and Cancer.

PMID- 20155613
TI  - Selected aspects of Mediterranean diet and cancer risk.
AB  - European Mediterranean populations have a high life expectancy. Several aspects
      of their diet are considered favorable on health. We considered the role of
      various aspects of the Mediterranean diet on cancer risk in a series of Italian
      case-control studies including about 10,000 cases of cancer at 13 different sites
      and over 17,000 controls. For most epithelial cancers, the risk decreased with
      increasing vegetable consumption. Allium vegetables were also favorably related
      to cancer risk. Fruit intake was inversely associated with digestive tract and
      laryngeal cancers. For digestive tract cancers, the population attributable risks
      for low intake of vegetables and fruit ranged between 15% and 40%. Olive oil and
      unsaturated fats, which are typical aspects of the Mediterranean diet, were
      inversely related to the risk of several cancers, particularly of the upper
      aerodigestive tract. Whole grain food (and hence possibly fiber) intake was also
      related to reduced risk of various cancers. In contrast, refined grains and,
      consequently, glycemic load and index were associated to increased risks. Several
      micronutrients and food components (including folate, flavonoids, and
      carotenoids) showed inverse relations with cancer risk, but the main component(s)
      responsible for the favorable effect of a diet rich in vegetables and fruit
      remain undefined.

PMID- 20155614
TI  - Beta-carotene and lung cancer in smokers: review of hypotheses and status of
      research.
AB  - A number of epidemiological studies have reported associations of beta-carotene
      plasma levels or intake with decreased lung cancer risk. However, intervention
      studies in smokers have unexpectedly reported increased lung tumor rates after
      high, long-term, beta-carotene supplementation. Recently, detailed analyses by
      stratification for smoking habits of several large, long-term intervention or
      epidemiological trials are now available. The ATBC study, the CARET study, the
      Antioxidant Polyp Prevention trial, and the E3N study provide evidence that the
      adverse effects of beta-carotene supplementation are correlated with the smoking
      status of the study participants. In contrast, the Physician Health Study, the
      Linxian trial, and a pooled analysis of 7 epidemiological cohort studies have not
      supported this evidence. The ferret and A/J mouse lung cancer model have been
      used to investigate the mechanism of interaction of beta-carotene with
      carcinogens in the lung. Both models have specific advantages and disadvantages.
      There are a number of hypotheses concerning the beta-carotene/tobacco smoke
      interaction including alterations of retinoid metabolism and signaling pathways
      and interaction with CYP enzymes and pro-oxidation/DNA oxidation. The animal
      models consistently demonstrate negative effects only in the ferret, and
      following dosing with beta-carotene in corn oil at pharmacological dosages. No
      effects or even protective effects against smoke or carcinogen exposure were
      observed when beta-carotene was applied at physiological dosages or in
      combination with vitamins C and E, either as a mixture or in a stable
      formulation. In conclusion, human and animal studies have shown that specific
      circumstances, among them heavy smoking, seem to influence the effect of high
      beta-carotene intakes. In normal, healthy, nonsmoking populations, there is
      evidence of beneficial effects.

PMID- 20155615
TI  - Lycopene effects contributing to prostate health.
AB  - Epidemiological evidence links lycopene consumption with decreased prostate
      cancer risk. Several signaling pathways have been identified as players in
      prostate cancer development. Chronic prostatitis, for example, due to infections,
      is a suggested risk factor for prostate cancer. Endogenous production of reactive
      oxygen species during inflammation may lead to oxidative DNA damage, which can be
      mutagenic, if unrepaired. Androgen signaling, cytokine (IL-6, IL-4) and growth
      factor signaling (e.g., IGF, Wnt/beta-catenin) cross-talk via PI3K/Akt, MAPK, and
      Jak/STAT pathways have been identified as major controllers of prostate growth.
      During disease progression, and after androgen ablation therapy, the remaining
      operational pathways are upregulated to compensate for the lost growth signal,
      finally resulting in androgen-independent prostate cancer. Lycopene modulates
      several of the aforementioned pathways, providing a promising rationale for
      prostate cancer risk reduction by lycopene: In many experimental setups, lycopene
      reduced inflammatory signals, prevented oxidative DNA damage, modulated the
      expression or activity of IGF axis members, of Wnt/beta-catenin and androgen
      signalling, and enhanced gap junctional communication. Lycopene's influence on
      these pathways likely contributes to the observed cell growth inhibition and
      apoptosis induction by lycopene. A substantial part of the lycopene effects can
      be explained by its antioxidant action, but other mechanisms might also be
      involved.

PMID- 20155616
TI  - Lycopene in the prevention of gastrointestinal toxicity of radiotherapy.
AB  - We conducted a study to investigate if lycopene could reduce gastrointestinal
      toxicity of abdominal and pelvic radiation in Wistar albino rats. Animals
      received either a control diet (Group 1), lycopene-supplemented diet (Group 2),
      control diet and radiation (Group 3), and lycopene-supplemented diet plus
      radiation (Group 4). In Groups 2 and 4, the rats received 5 mg/kg/day lycopene
      for 10 days. In Groups 3 and 4, the rats received single fraction 8 Gy abdominal
      and pelvic radiation (RT) on Day 10. Study endpoints included weight loss,
      diarrhea, duration of diarrhea, survival, and an oxidative stress marker, plasma
      level of thiobarbituric acid reactive substance (TBARS). The rats receiving RT
      only had significantly higher weight loss rate compared to the lycopene plus RT
      group (P = 0.001). Plasma TBARS levels after RT were also significantly higher in
      the RT only group compared to lycopene plus RT group (P = 0.001). In conclusion,
      lycopene supplementation significantly reduced the weight loss and prevented
      oxidative stress in rats treated with abdominopelvic radiation.

PMID- 20155617
TI  - Phytochemicals in hepatocellular cancer prevention.
AB  - Since the incidence of liver cancer is increasing in the world, it is valuable to
      develop an effective method for its prevention. Various phytochemicals have been
      shown to suppress liver carcinogenesis in experimental studies. Using these
      phytochemicals, a clinical trial was conducted. Combination of carotenoids and
      myo-inositol was found to prevent hepatocellular carcinoma development in
      patients with chronic viral hepatitis and cirrhosis.

PMID- 20155618
TI  - Early intake appears to be the key to the proposed protective effects of soy
      intake against breast cancer.
AB  - There is a large variation in breast cancer incidence and mortality rates
      worldwide. Migration studies have indicated that this variation is primarily the
      result of lifestyle influences. Although there has been much research conducted,
      definitively identifying dietary factors that impact breast cancer risk has
      proven difficult. In part this may be because most clinical and epidemiologic
      studies have focused on adult dietary exposure. However, evidence suggests that
      childhood and/or adolescence is the period of life when the breast is most
      sensitive to dietary influences. Further, the available epidemiologic and animal
      data suggest that early soy intake reduces breast cancer risk. Soy foods are
      unique dietary sources of isoflavones, diphenolic compounds that exert estrogen
      like effects under certain experimental conditions. The protection effects of soy
      may result from the soybean isoflavones stimulating differentiation of the breast
      in much the same way that the elevated estrogen levels do during pregnancy. More
      specifically, in rats, the primary isoflavone genistein reduces mammary
      tumorigenesis and increases mammary tissue differentiation by leading to a
      reduction in the number of terminal end buds (TEB) and an increase in the number
      of differentiated lobules. There is need and justification for continued
      investigation of the early soy intake hypothesis, particularly to determine the
      cellular targets of soy action and to identify the signaling pathways mediating
      the effects on mammary gland morphology and susceptibility to breast cancer.

PMID- 20155619
TI  - Genistein suppresses spontaneous oviduct tumorigenesis in quail.
AB  - Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail
      (Coturnix coturnix japonica) and laying hens. This makes it a good animal model
      for screening potential agents for testing in the prevention and treatment of
      human myoma uteri. Genistein has been shown to inhibit the growth of various
      cancer cells. We investigated the effects of genistein supplementation on the
      development of fibroid tumors in the oviduct, serum oxidative stress markers
      [malondialdehyde (MDA), 8-isoprostane, 4-hydroxyalkenal (HAE), 8-hydroxy-2' 
      deoxyguanosine (8-OHdG) levels], soy isoflavone levels, and tissue biomarkers
      [Connexin 43 (Cx43), Bcl-2, and Bax and heat shock protein 70 (Hsp70) expression]
      in Japanese quail. One hundred and fifty quail (12 mo old) were assigned to 3
      experimental groups as 5 replicates of pens containing 10 birds in each. Birds
      were fed either a basal diet or the basal diet supplemented with 400 mg or 800 mg
      of genistein/kg of diet. The animals were sacrificed after 315 days, and the
      tumors were identified. Genistein supplementation significantly decreased the
      incidence of fibroid tumors as compared to control birds (P = 0.04). The tumors
      in genistein-fed birds were smaller than those found in control birds (P = 0.02).
      Serum MDA, 8-isoprostane, and HAE levels were lower in treatment groups than in
      control group (MDA: 2.01 vs. 0.82; 8-isoprostane: 135 vs. 101; HAE: 1.45 vs.
      0.73; P <or= 0.01). The concentrations of serum 8-OHdG, which is a marker of
      oxidative damage, in the groups were 27.5, 22.4, and 21.3 ng/ml, respectively (P
      = 0.05). The expression of cell cycle regulatory proteins, Bcl-2, was 4.18 and
      4.61 in the genistein groups and 6.21 in the control group, and the expression of
      Bax was 10.93 and 16.78 in the genistein groups and 7.60 in the control group (P
      < 0.001 for Bax). Cx43 level was 2.56 and 2.40 in the genistein groups compared
      with 5.15 in the control group. None of the differences in the Cx43 and Bcl-2 of
      the groups were significant. The expression of heat shock proteins, Hsp60 and
      Hsp70, were not different between groups, although Hsp70 level of the genistein
      groups (19.73) was lower than the control group (27.8). The results indicate that
      dietary supplementation of genistein reduces the incidence and size of
      spontaneously occurring leiomyoma of the oviduct in the Japanese quail. Clinical
      trials should be conducted to investigate the efficacy of genistein
      supplementation in the prevention and treatment of uterine leiomyoma in humans.

PMID- 20155620
TI  - Dietary polyphenols, inflammation, and cancer.
AB  - A considerable amount of evidence indicates that tumorigenesis is associated with
      inflammation. Nuclear factor-kappa B (NF-kappa B), a master regulator of
      infection and inflammation, has been identified as a key modulator in which
      inflammation could develop into cancer. Dietary polyphenols have been shown to
      have anti-inflammatory and anticancer activity partially through inhibition of NF
      kappa B activation. This review summarizes the effect of polyphenols on
      inflammation and cancer; avenanthramides, a unique polyphenol from oats, are
      especially focused.

PMID- 20155621
TI  - Cancer chemoprevention by pomegranate: laboratory and clinical evidence.
AB  - Pomegranate fruit from the tree Punica granatum has been dubbed as the "nature's
      power fruit." Dating back to Biblical times, the tree itself is attributed to
      possess extraordinary medicinal properties. The geographical distribution of the
      tree, being native to the Middle East and some Asian countries, is generally
      attributed to a lack of interest in its medicinal properties by many western
      scientists. However, the unique biochemical composition of the pomegranate fruit
      being rich in antioxidant tannins and flavonoids has recently drawn attention of
      many investigators to study its exceptional healing qualities. Recent research
      has shown that pomegranate extracts selectively inhibit the growth of breast,
      prostate, colon and lung cancer cells in culture. In preclinical animal studies,
      oral consumption of pomegranate extract inhibited growth of lung, skin, colon and
      prostate tumors. An initial phase II clinical trial of pomegranate juice in
      patients with prostate cancer reported significant prolongation of prostate
      specific antigen doubling time. This review focuses on recent investigations into
      the effects of pomegranate fruit on cancer.

PMID- 20155622
TI  - Black raspberry components inhibit proliferation, induce apoptosis, and modulate
      gene expression in rat esophageal epithelial cells.
AB  - We have shown that a diet containing freeze-dried black raspberries (BRB)
      inhibits the development of chemically induced cancer in the rat esophagus. To
      provide insights into possible mechanisms by which BRB inhibit esophageal
      carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two component
      anthocyanins (cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside) in BRB, for
      their effects on growth, apoptosis, and gene expression in rat esophageal
      epithelial cell lines. The EtOH extract and both anthocyanins selectively caused
      significant growth inhibition and induction of apoptosis in a highly tumorigenic
      cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149). The uptake
      of anthocyanins from the EtOH extract into RE-149 DHD cells far exceeded their
      uptake into RE-149 cells, which may have accounted for the selective effects of
      the extract on growth and apoptosis of RE-149 DHD cells. The growth inhibitory
      and proapoptotic effects were enhanced by the daily addition of the EtOH extract
      and the anthocyanins to the medium. Interestingly, the EtOH extract did not alter
      cyclooxygenase-2 (COX-2) and nitric oxide synthase (i-NOS) expression in RE-149
      DHD cells, whereas both anthocyanins downregulated the expressions of these
      genes. This differential effect may have been related to the relative amounts of
      anthocyanins in the extract vs. when they were added individually to the medium.
      We conclude that the selective effects of the EtOH extract on growth and
      apoptosis of highly tumorigenic rat esophageal epithelial cells in vitro may be
      due to preferential uptake and retention of its component anthocyanins, and this
      may also be responsible for the greater inhibitory effects of freeze-dried whole
      berries on tumor cells in vivo.

PMID- 20155623
TI  - Molecular mechanisms of green tea polyphenols.
AB  - Tea, next to water, is the most popular beverage in the world. It has been
      suggested that tea consumption has the cancer-preventive effects. Epidemiological
      studies have indicated decreased cancer occurrence in people who regularly drink
      green tea. Research has also discovered numerous mechanisms of action to explain
      the biological effects of tea. The most abundant and popular compound studied in
      tea research is (-)-epigallocatechin-3-gallate or (-)-EGCG, which is a powerful
      antioxidant and can inhibit a number of tumor cell proliferation and survival
      pathways. Tea polyphenols are known to inhibit metaloproteonases, various protein
      kinases, and proteins that regulate DNA replication and transformation. We also
      reported that ester bond-containing tea polyphenols, for example, (-)-EGCG,
      potently and specifically inhibited the tumor proteasomal activity. We further
      demonstrated that methylation on green tea polyphenols under physiological
      conditions decreased their proteasome-inhibitory activity, contributing to
      decreased cancer-preventive effects of tea consumption. Since (-)-EGCG is
      unstable under physiological conditions, we also developed the peracetate
      protected or prodrug form of (-)-EGCG, Pro-EGCG (1), and showed that Pro-EGCG (1)
      increases the bioavailability, stability, and proteasome-inhibitory and
      anticancer activities of (-)-EGCG in human breast cancer cells and tumors,
      demonstrating its potential use for cancer prevention and treatment.

PMID- 20155624
TI  - Review: green tea polyphenols in chemoprevention of prostate cancer: preclinical
      and clinical studies.
AB  - The prevention of prostate cancer (PCa) is a crucial medical challenge in
      developed countries. PCa remains surrounded by puzzles in spite of the
      considerable progress in research, diagnosis, and treatment. It is an ideal
      target for chemoprevention, as clinically significant PCa usually requires more
      than two decades for development. Green tea and its major constituent
      epigallocatechin gallate (EGCG) have been extensively studied as a potential
      treatment for a variety of diseases including cancer. In this review, we
      highlight the evidences of green tea polyphenols from preclinical and clinical
      studies in the chemoprevention/chemotherapy of PCa.

PMID- 20155625
TI  - Synergistic role of curcumin with current therapeutics in colorectal cancer:
      minireview.
AB  - Despite the use of surgical resection and aggressive chemotherapy, nearly 50% of
      patients with colorectal carcinoma develop recurrent disease, highlighting the
      need for improved therapies. Curcumin (diferuloylmethane), the major active
      ingredient of turmeric (curcuma longa) with no discernable toxicity, has been
      shown to inhibit the growth of transformed cells and colon carcinogenesis at the
      initiation, promotion, and progression stages in carcinogen-induced rodent
      models. In a Phase I clinical trial, curcumin has been found to be extremely well
      tolerated and effective. In this review, we summarized the current status of our
      knowledge about the effectiveness of curcumin when given in combination with
      current chemotherapeutics such as 5-fluorouracil, oxaliplatin, and gemcitabine in
      treatment of gastrointestinal cancers with particular reference to colorectal
      cancer. Existing data suggest that curcumin in combination with chemotherapy is a
      superior strategy for treatment of gastrointestinal cancer.

PMID- 20155626
TI  - Resveratrol and piceatannol inhibit iNOS expression and NF-kappaB activation in
      dextran sulfate sodium-induced mouse colitis.
AB  - Inflammatory tissue injury has been implicated in tumor promotion and
      progression. 3,5,4'-trihydroxy-trans-stilbene (resveratrol) and 3,4,3', 5'
      tetrahydroxy-trans-stilbene (piceatannol), 2 structurally related plant
      polyphenols, have been reported to possess antioxidant, anti-inflammatory, and
      chemopreventive properties. This study was aimed at investigating the possible
      protective effects of resveratrol and piceatannol against dextran sulfate sodium
      (DSS)-induced inflammation in mouse colonic mucosa. Administration of DSS (2.5%)
      in drinking water for 7 days to male ICR mice resulted in colitis and elevated
      expression of inducible nitric oxide synthase (iNOS) and activation of nuclear
      factor-kappa B (NF-kappaB), a major transcription factor known to upregulate
      proinflammatory gene expression. Phosphorylation of extracellular signal
      regulated kinase (ERK) and signal transducer and activator of transcription-3
      (STAT3) was also enhanced after DSS treatment. Oral administration of resveratrol
      or piceatannol (10 mg/kg body weight each) for 7 constitutive days attenuated the
      DSS-induced inflammatory injury, upregulation of iNOS expression, and activation
      of NF-kappaB, STAT3, and ERK.

PMID- 20155627
TI  - Piceatannol inhibits phorbol ester-induced NF-kappa B activation and COX-2
      expression in cultured human mammary epithelial cells.
AB  - There are multiple lines of evidence supporting that inflammation is causally
      linked to carcinogenesis. Abnormal upregulation of cyclooxygenase-2 (COX-2), a
      rate-limiting enzyme in the prostaglandin biosynthesis, has been implicated in
      carcinogenesis. Trans-3,4,3',5'-tetrahydroxystilbene (piceatannol), a naturally
      occurring hydroxylated stilbene with potent anti-inflammatory and antioxidative
      activities, has been shown to inhibit the proliferation of several cancer cells
      by inducing apoptosis or blocking cell cycle progression. In this study, we
      examined the effect of piceatannol on activation of the nuclear transcription
      factor NF-kappa B, one of the major transcription factors that regulate
      proinflammatory COX-2 gene transcription, in human mammary epithelial (MCF-10A)
      cells treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA).
      When pretreated to MCF-10A cells, piceatannol markedly inhibited TPA-induced NF
      kappa B DNA binding to a greater extent than resveratrol and oxyresveratrol,
      stilbene analogs structurally related to piceatannol. Piceatannol also inhibited
      TPA-induced phosphorylation and degradation of Ikappa Balpha as well as nuclear
      translocation of the phosphorylated form of p65, the functionally active subunit
      of NF-kappa B. Likewise, TPA-induced expression of COX-2 was abrogated by
      piceatannol pretreatment. The thiol reducing agent dithiothreitol abolished the
      inhibitory effects of piceatannol on NF-kappa B DNA binding activity, suggesting
      that piceatannol may directly modify NF-kappa B or its regulator through reaction
      with the cysteine thiol(s).

PMID- 20155628
TI  - Induction of caspase-independent programmed cell death by vitamin E natural
      homologs and synthetic derivatives.
AB  - Current observations in the literature suggest that vitamin E may be a suitable
      candidate for cancer chemotherapy. To investigate this further, we examined the
      ability of the vitamin E natural homologs [alpha-, beta-, gamma-, delta
      tocopherols (alpha-TOC, beta-TOC, gamma-TOC, delta-TOC) and alpha-, beta-, gamma
      , delta-tocotrienols (alpha-TT, beta-TT, gamma-TT, delta-TT)] and their
      corresponding succinate synthetic derivatives [alpha-, beta-, gamma-, delta
      tocopheryl succinates and alpha-, beta-, gamma-, delta-tocotrienyl succinates
      (alpha-TS, beta-TS, gamma-TS, delta-TS)] to induce cell death in AR- (DU145 and
      PC3) and AR+ (LNCaP) prostate cancer cell lines. The most effective of all the
      natural homologs of vitamin E was determined to be delta-TT, whereas delta-TS was
      the most potent of all the natural and synthetic compounds of vitamin E examined.
      Both gamma-TT and delta-TT induced caspase activity selectively in AR+ LNCaP
      cells, suggesting a possible role for AR for the activation of caspase-dependent
      programmed cell death (CD-PCD). More important, however, gamma-TT, delta-TT,
      gamma-TS, and delta-TS activated dominant caspase-independent programmed cell
      death (CI-PCD) in all prostate cancer cell lines examined. Thus, vitamin E
      homologs and synthetic derivatives may find applications in the treatment of
      prostate tumors that are resistant to caspase-activating therapeutic agents.

PMID- 20155629
TI  - Vitamin E and cancer.
AB  - Protection by vitamin E against free radical-induced DNA mutations appears not to
      be an effective occurrence. On the other hand, in vitro evidence that different
      tocopherols slow down cell proliferation is an accepted observation. However,
      such an event may not be sufficient to result in beneficial clinical outcomes.
      Tocopheryl phosphate, a more active, natural derivative of tocopherol, endowed
      with prevention and therapeutic potential, represents a possible key to the
      understanding of the present conflict between laboratory and clinical results.

PMID- 20155630
TI  - Zinc in cancer prevention.
AB  - Essentiality of zinc for humans was discovered 45 yr ago. Deficiency of zinc is
      prevalent world wide in developing countries and may affect nearly 2 billion
      subjects. The major manifestations of zinc deficiency include growth retardation,
      hypogonadism in males, cell-mediated immune dysfunctions, and cognitive
      impairment. Zinc not only improves cell mediated immune functions but also
      functions as an antioxidant and anti-inflammatory agent. Oxidative stress and
      chronic inflammation have been implicated in development of many cancers. In
      patients with head and neck cancer, we have shown that nearly 65% of these
      patients were zinc deficient based on their cellular zinc concentrations. Natural
      killer (NK) cell activity and IL-2 generation were also affected adversely. Th2
      cytokines were not affected. In our patients, zinc status was a better indicator
      of tumor burden and stage of disease in comparison to the overall nutritional
      status. Zinc status also correlated with number of hospital admissions and
      incidences of infections. NF-kappa B is constitutively activated in many cancer
      cells, and this results in activation of antiapoptotic genes, VEGF, cyclin DI,
      EGFR, MMP-9 and inflammatory cytokines. Zinc inhibits NF-kappa B via induction of
      A-20. Thus, zinc supplementation should have beneficial effects on cancer by
      decreasing angiogenesis and induction of inflammatory cytokines while increasing
      apoptosis in cancer cells. Based on the above, we recommend further studies and
      propose that zinc should be utilized in the management and chemoprevention of
      cancer.

PMID- 20155631
TI  - Zinc and selenium status in pediatric malignant lymphomas.
AB  - Ninety-six untreated patients with malignant lymphoma (ML), 81 Hodgkin's disease,
      and 15 Burkitt's lymphoma were studied for zinc (Zn) status, and 21 patients also
      had selenium (Se) status analysis. Plasma and hair Zn and Se levels were measured
      by atomic absorption spectrophotometry. Chronic Zn and Se deficiencies (low
      plasma and low hair Zn and Se levels together) were found to be associated with
      ML in Turkish children. This was most likely due to the poor "nutritional
      environment" of the patients because majority of the ML patients were from
      families of low socioeconomic status. Supplementation of pediatric ML patients
      with Zn and Se, in addition to standard chemotherapy and radiotherapy regimen, is
      recommended.

PMID- 20155632
TI  - Avemar (wheat germ extract) in cancer prevention and treatment.
AB  - Many healthy foods are derived from wheat germ. The molecular composition of
      these products, however, greatly differs as shown by normal-phase HPLC-mass
      spectrometry analysis; thus, experimental data obtained by one of them is not
      necessarily true for the other. Avemar is a nontoxic wheat germ extract
      registered as a special nutriment for cancer patients in Hungary. It shows potent
      anticancer activity on cell lines by deeply interfering with glucose metabolism
      and affecting expressions of several kinases. In in vivo experimental models,
      Avemar is also effective by enhancing the activity of the immune system such as
      stimulating NK cell activity (by reducing MHC I molecule expression), enhancing
      TNF secretion of the macrophages, increasing ICAM 1 molecule expression on the
      vascular endothelial cells. All of these lead to apoptosis of tumor cells. The
      wide range of biological activity of Avemar probably cannot be explained by only
      one active ingredient. Since there are numerous experimental data and the
      clinical benefit repeatedly confirmed Avemar can be one of the most potent and
      best researched food supplements available for cancer patients.

PMID- 20155633
TI  - Nutrition and gastric cancer in Turkey.
AB  - Gastric cancer remains to be one of leading causes of cancer deaths despite
      worldwide decreasing incidence. In Turkey gastric cancer incidence is 9.6/100,000
      in men and 5.7/100,000 in females. Gastric cancer is also one of the leading
      causes of cancer deaths in Turkey with a crude death rate of 5.84/100,000 in men,
      3.7/100,000 in women. The mean age of patients diagnosed with gastric cancer is
      56 years in Turkey. The relatively high rate of gastric cancer in Turkey is
      mainly due to dietary factors. The traditional food preservation such as salt
      curing or smoking and lack of refrigeration of food play a significant role in
      gastric cancer development in the country. There are etiological and
      epidemiological differences among geographical regions in Turkey. Gastric cancer
      is seen much more often in the central, northeastern, and eastern part of Turkey.
      Increased HP pylori infection is also another important reason for increased
      incidence of gastric cancer in some parts of the country.

PMID- 20155634
TI  - Bandaru S. Reddy: in memoriam (1930-2009).

PMID- 20155636
TI  - [First therapy of decompression injuries].
AB  - The diving accident is a rare incident for an emergency physician which requires
      special physical and patho-physiological knowledge. With increasing recreational
      activities and the fascination of diving also for older persons diving accidents
      are expected to occur more often. There can be several reasons for diving
      accidents such as the ignorance of the physics of diving, a trauma under water as
      well as internistical illnesses like heart attach, stroke or hypoglycaemia. The
      therapy of the underlying illness should not be left aside while dealing with the
      patient. The careful rescue and the immobilisation are most important for the
      initial therapy. The patient should receive oxygen, if possible via a demand
      valve, until a hyperbaric chamber is reached. There is no specific medical
      therapy for decompression illness. It is very important that a pre-information is
      sent to the closest hyperbaric chamber as soon as possible since often the
      chamber needs some time to be properly prepared for usage. In order to receive
      information regarding the depth where the diving incident occured, the duration
      of the diving trip and the decompression stops, it is important to secure the
      diving computer of the victim for the hyperbaric chamber. Also outside diving,
      decompression illness can occur, for example working in a tunnel under hyperbaric
      conditions. These accidents have to be treated according to the same guidelines.

PMID- 20155638
TI  - [Quality characteristics concerning pain therapy].
AB  - The Institute of Medicine (IOM) reports "Crossing the Quality Chasm proposed 7
      aims for high-quality healthcare: effective, safe, timely, efficient, equitable,
      patient-centred, and emphasized care coordination. The quality of pain treatment
      can also be shown by structure quality, process quality, and outcome quality. The
      present investigation shows methods of the qualitative capture of pain therapy.
      On this occasion, it is shown whether such a pain measurement with the available
      parameters is generally possible and which parameters are necessary for this.
      However, quality parameter and quality outcome must be regarded individually for
      every patient. Quality measurement concerning the therapy of chronic pain
      diseases is an interaction of several quality and outcome parameters. Furthermore
      patients' aims concerning his individual pain treatment must be taken into
      account.

PMID- 20155637
TI  - [Ambulatory pain therapy in penetrating rectal cancer via epidural anesthesia].
AB  - Treatment of cancer pain includes invasive techniques of pain therapy if
      necessary. Here we report the management of a 55-year-old female patient with
      penetrating rectal cancer using continuous lumbal epidural anesthesia. After
      placement and dose-finding our patient was discharged from hospital and further
      treatment occurred at home.

PMID- 20155639
TI  - [Postoperative delirium and cognitive deficit. Just don't lose your head!].

PMID- 20155640
TI  - [If delirium is not monitored it will often be not detected].
AB  - The reported incidence of delirium in critically ill patients ranges widely -
      from 11% to 87%. Both in the recovery room as well as in the intensive care unit
      postoperative delirium is the most common psychiatric disease. Patients with ICU
      delirium have a significant higher 6-month mortality rate. Recent studies could
      show that the use of a validated delirium assessment tool significantly improves
      the ability of physicians and nurses to detect delirium in ICU patients. The
      following article gives a review about different assessment tools of ICU delirium
      and focuses on the differences between validated delirium scores.

PMID- 20155641
TI  - [Postoperative delirium and cognitive deficit. Prevention and therapy].
AB  - To date, there are few studies available focusing on prevention and therapy of
      delirium in ICU patients. Monitoring during routine care is important because
      without using validated tools only one third of the delirious patients will be
      detected. A lot of non-pharmacological interventions like re-orientation and
      helping the patient to get back his autonomy, but also goal-orientated sedation
      support prevention and therapy of delirium. Furthermore, there are hints that
      pharmacological intervention can reduce incidence and severity of delirium. For
      delirium prevention there are drugs available acting on different receptor
      systems (acetylcholine, dopamine, opioid, glutamate). For the use of this drugs,
      a strict risk-benefit-consideration is necessary due to the low level of evidence
      of the existing studies. Therapeutically causative and symptom-orientated
      approaches should be preferred.

PMID- 20155642
TI  - [Postoperative delirium and cognitive deficit. Routine delirium monitoring in the
      intensive care unit].
AB  - Up to 92% of patients in ICU develop delirium, which may be missed without
      routinely monitoring. Delirium monitoring, though, is often deemed time consuming
      and dispensable, as mere clinical judgement is considered sufficient. This paper
      describes the general pitfalls during the introducing of a delirium screening
      tool and provides tips for daily delirium monitoring.

PMID- 20155643
TI  - [Economy and ethics in daily hospital routine - physicians in conflict between
      the well-being of patients and profitability].
AB  - Medical decision making is affected by different aims and influencing factors.
      Nowadays economic aspects are so important that they influence the structure of
      hospitals, the number and quality of personnel, and the treatment and care of
      patients. This leads to conflicts with moral aims, especially when the necessary
      service cannot be provided due to financial reasons or when doubtful offers are
      supposed to increase revenues. Examples demonstrate cases in which economic
      aspects become more important than patients' interests because physicians are
      corruptible. It is necessary to communicate values. Patients' health should be
      first and economy should be a subordinated service.

PMID- 20155644
TI  - [Patient care according to the latest state of the science--implications of
      evidence-based medicine].
AB  - Evidence-based medicine implies that recommendations ideally exist for each
      clinical question based on a systematic data search in the current literature, a
      data extraction, a summary and critical appraisal. Over the last fifty years
      evidence-based medicine has been growing rapidly. Systematic reviews and
      randomised controlled trials are of high impact in this field. However, the
      question remains: in which way is daily clinical practice affected? In an era of
      time- and cost-pressures as well as manpower shortages, the complex process of
      evidence-based medicine is difficult. Examples from perioperative pain therapy
      are provided to demonstrate how evidence-based medicine could be feasible and
      incorporated into daily practice.

PMID- 20155646
TI  - [Foreign body ingestion in children: recommendation for the diagnostic and
      therapeutic procedure].
AB  - Because many children who have swallowed foreign bodies are asymptomatic,
      physicians must maintain a high index of suspicion. The majority of ingested
      foreign bodies pass spontaneously, but serious complications, such as bowel
      perforation and obstruction, can occur. There is only limited evidence based data
      on the diagnostic and therapeutic procedure. In german speaking countries no
      treatment recommendations or guidelines exist. We present an interdisciplinary
      consented flow sheet for the diagnostic and therapeutic procedure for the
      gastrointestinal ingestion of radiolucent and radiodense foreign bodies, which is
      based on the available data as well as on common sense.

PMID- 20155648
TI  - [Anaesthesiological responsibility at bleeding after tonsillectomy].

PMID- 20155649
TI  - [The significance of perioperative immunonutrition].
AB  - Perioperative immunonutrition is aiming at modulating altered immunological and
      metabolic functions in the context of major surgery. It is defined as the
      supplementation of constitutionally essential substrates such as glutamine,
      arginine, omega-3-fatty acids or nucleotides. The application of such formula is
      recommended for patients undergoing major abdominal-surgical procedures and
      tumour surgery in the head neck area. The substitution should be given 5-7 days
      before and after the intervention.

PMID- 20155650
TI  - [Neovascular glaucoma].

PMID- 20155651
TI  - [New pathophysiological aspects for glaucoma].

PMID- 20155652
TI  - [Oxidative tissue damage].
AB  - Oxidative stress is defined as an overflow of oxidative metabolites either in the
      human body or in a compartment of the body. Today this chemical definition has
      been slightly modified and encompasses an elevation of oxidative metabolites or a
      relative deficiency of anti-oxidants. Molecular oxygen is the basis of many
      highly reactive oxidative species which are able to directly damage or lead to
      the generation of secondary reactions which then initiate oxidative processes.
      The cell has established numerous mechanisms and strategies to antagonise those
      oxidative processes at different steps. Many diseases have been shown to be
      either related to or even be initiated by oxidative processes. The eye is at high
      risk to be damaged by oxidative mechanisms. One major reason is its permanent
      exposition to oxidative stimuli. The biochemical composition of ocular
      structures, especially that of the retina (unsaturated fatty acids), is an
      important factor making the eye more susceptible as compared to other organs.
      Ocular ischaemia, ischaemia or hypoxia of the retina, diabetic retinopathy and
      glaucoma are important disease entities that are initiated or propagated by
      oxidative processes. Ischaemic processes lead to classical reactions of the
      oxidative pathway. This is no longer believed to be the case in diabetic
      retinopathy. Here, advanced glycation end products (AGE's) and related species
      are able to induce oxidative reactions and the expression of growth factors. In
      age-related macular degeneration, photodynamic processes that already occur in
      childhood are believed to be a major factor contributing to the pathogenesis of
      the disease process. In addition, the expression of growth factors and new vessel
      growth can be initiated via inflammatory reactions or oxidative metabolites.

PMID- 20155653
TI  - [Oxidative stress in the trabecular meshwork of POAG].
AB  - Primary open angle glaucoma (POAG) is defined as an optic neuropathy which is
      characterised by the loss of optic nerve axons and the related retinal ganglion
      cells. The reason for these changes is still unknown. In the pathogenesis of POAG
      several factors like increased intraocular pressure and a reduction of ocular
      blood supply are discussed. Morphological and biochemical analyses of the
      trabecular meshwork (TM) of POAG patients revealed loss of cells, increased
      accumulation of extracellular matrix (ECM), changes in the cytoskeleton, cellular
      senescence and the process of subclinical inflammation. One factor becoming more
      likely to be involved in the pathogenesis of POAG is oxidative stress. Treatment
      of TM cells with oxidative stress induced POAG-typical changes like ECM
      accumulation, cell death, disarrangement of the cytoskeleton, advanced senescence
      and the release of inflammatory markers. By pretreatment with antioxidants,
      prostaglandin analogues, beta-blockers or local carbonic anhydrase inhibitors,
      these effects were markedly reduced. In conclusion, oxidative stress is able to
      induce characteristic glaucomatous TM changes in vitro and these oxidative stress
      induced TM changes can be minimised by the use of antioxidants and IOP-lowering
      substances. It is tempting to speculate that prevention of oxidative stress
      exposure to the TM may help to reduce the progression of POAG.

PMID- 20155654
TI  - [Oxidative stress and pseudoexfoliation glaucoma].
AB  - Pseudoexfoliation (PEX) glaucoma is the most common identifiable cause of open
      angle glaucoma worldwide, comprising the majority of glaucoma in some countries.
      The underlying disorder, PEX syndrome, is a generalised, genetically determined,
      elastotic process of the extracellular matrix characterised by the excessive
      production and progressive accumulation of a fibrillar material in various
      tissues including the outflow pathways. Increasing evidence suggests that the
      oxidative-antioxidative balance is disturbed in patients with PEX
      syndrome/glaucoma, both in the anterior segment and throughout the body, and that
      the resulting oxidative stress constitutes a major mechanism involved in the
      pathophysiology of this fibrotic process. Significantly reduced levels of
      antioxidants, such as ascorbic acid, glutathione, trace elements, antioxidative
      enzymes, and total antioxidative capacity in aqueous humor and serum suggest a
      faulty antioxidative defense system in PEX patients. The down-regulation of
      antioxidative enzymes in anterior segment tissues also indicates an inadequate
      cytoprotection against oxidative stress. Concomitantly, levels of oxidants such
      as hydrogen peroxide or nitric oxide, and oxidative stress markers, including
      lipid peroxidation products, degradation products of oxidated and methylated
      proteins, advanced glycation end products, and homocysteine are significantly
      increased in aqueous humor, tissues, and serum. The available data suggest that
      chronic oxidative stress in combination with weakened cytoprotective and repair
      strategies affects the abnormal matrix metabolism by induction of a persistent
      pro-inflammatory state and activation of the profibrotic growth factor TGF-beta1.
      Oxidative stress, therefore, appears to represent a modifiable risk factor in the
      management of patients with PEX syndrome/glaucoma.

PMID- 20155655
TI  - [Relationship between oxidatve stress and autoimmunity in glaucoma].
AB  - Elevated intraocular pressure does not explain glaucoma in all patients, but
      there is information that autoimmune mechanisms may be involved in this disorder.
      We have demonstrated in several studies that glaucoma patients reveal changes in
      their immune reactivities against ocular antigens. The mechanisms of these
      reactivities are still widely unknown, but oxidative pathways could play a major
      role. There is evidence that free radicals are able to alter the ability of glial
      cells to be recognized as antigens. Furthermore, one can assume that during the
      aging process posttranslational changes, e. g., oxidation of ocular antigens
      increase with age. It is feasible that these changed antigens may trigger such
      changes. in an autoimmune glaucoma animal model we have shown that immunological
      processes after immunisation can lead to a loss of retinal ganglion cells.
      Considering that these changes in natural autoimmunity can be found consistently
      amongst different study populations, it might be a promising new tool for
      glaucoma diagnosis and new therapeutic immunomodulating options.

PMID- 20155656
TI  - [Importance of the nuclear factor kappaB for the primary open angle glaucoma--a
      hypothesis].
AB  - The primary open-angle glaucoma (POAG) is an optic neuropathy which is influenced
      by a number of different risk factors. Some of them can induce the
      transcriptional factor NF-kappaB, a nuclear protein which binds to specific areas
      of the DNA to stimulate different genes. NF-kappaB can be activated by increased
      intraocular pressure, increased age, vascular diseases and by oxidative stress.
      In the case of POAG NF-kappaB might be overstimulated with the induction of
      uncontrolled biochemical reactions. Treatment strategies for reducing NF-kappaB
      are to reduce intraocular pressure as well as therapies with statins, omega-3
      fatty acids and alpha-lipoic acid. This model is a hypothesis and is intended to
      provide a basis for further discussions and basic research.

PMID- 20155657
TI  - [Frequency of posterior vitreous detachment as determined intraoperatively in
      patients with an idiopathic epiretinal membrane].
AB  - INTRODUCTION: The prevalence of a posterior vitreous detachment in patients with
      an idiopathic epiretinal membrane is often exaggerated in the literature. This
      may make the surgeon become overconfident during vitrectomy. PATIENTS AND
      METHODS: 34 patients with an idiopathic epiretinal membrane (mean age 72.9 years)
      were vitrectomised. The membrane and with it the remaining vitreous were stained
      with Membrane Blue. RESULTS: The preoperative visual acuity was -0.6 +/- 0.176
      logMar units. Visual acuity increased postoperatively to -0.3 +/- 0.252 logMar
      units after 372.6 days. A posterior vitreous detachment was found in 17 patients
      (50 %), whereas there was none in the remaining 50 %. There was no correlation
      between age and prevalence of vitreous detachment. DISCUSSION: The increase in
      visual acuity was very encouraging. In contrast to reports in the older
      literature one cannot expect to find a posterior vitreous detachment in patients
      with an idiopathic epiretinal membrane. This can be checked intraoperatively very
      easily with Membrane Blue. Such a check becomes more urgent as the posterior
      vitreous detachment cannot be achieved with 23-G vitrectomy as easily as with 20
      G vitrectomy.

PMID- 20155658
TI  - [Glued eyelids by cyanoacrylate glue (superglue)].

PMID- 20155660
TI  - [Non-pharmacological therapy of chronic heart failure: the role of structured
      training programmes].

PMID- 20155661
TI  - [A new approach to quantitative electronic foetal heart-rate analysis].
AB  - BACKGROUND: Recently it was found that a significant correlation exists between
      the variables of the foetal acid-base balance (ABB) and the parameters of the
      foetal heart rate (FHR). This dependency can be used for diagnostic purposes.
      Until now FHR could be evaluated off- and online by computer using scoring
      procedures, i. e., discontinuous methods, which need considerable computational
      efforts since FHR must reliably be separated into baseline (BL), decelerations
      and accelerations. Therefore, the question must arise whether a continuous and
      less cumbersome evaluation of individual FHR-parameters might lead to even better
      results? METHODS: The last 30 min of 465 direct recordings of foetuses all
      delivered by the vaginal route were stored in a computer and analysed offline
      using our own MATLAB programmes. Five variables were computed for every single
      minute: The microfluctuation, the oscillation amplitude, the mean frequency, the
      sum of the absolute differences of time periods and the sum of the absolute
      differences of frequencies. In this paper the last two variables will be
      abbreviated 'total sums'. All minutes of a FHR tracing were treated equally i. e.
      there was no separation anymore between BL and decelerations (accelerations). In
      order to analyse the physiological intercorrelation of the five variables
      mentioned above a 'pH window' was chosen between 7.275 and 7.325 [7.275< or =pH,
      (umbilicalartery (UA)< or =7.325]. Thereafter, the influence of hypoxia and
      acidosis on the five variables was evaluated. According to the results obtained
      two of the five variables, the 'total sums', were not further analysed. Using the
      remaining variables 'frequency', 'oscillation amplitude' and 'microfluctuation' a
      new index, the WAS index, was created. This index offers the opportunity to
      evaluate the FHR continuously using 'coding lines' for each of the three
      parameters. The WAS index was designed according to the FHR characteristics of
      the awake (Wach), acidotic (Azidotisch) (pH, UA=ca. 7,000) and sleeping
      (Schlafend) foetus. Using the last 30 WAS indices covering the last 30 min of a
      single FHR tracing, a WAS score and the corresponding prognostic pH value was
      computed. These prognostic pH values were compared with the measured pH values of
      UA blood using again correlation analysis. RESULTS: Without any hypoxia and
      acidosis (pH, UA window) the five FHR variables are closely correlated with each
      other. Accepting minutes with decelerations only, the correlation between the
      'total sums' and the remaining three parameters vanishes. Accepting hypoxia and
      acidosis (pH, UA > or =6.960) oscillation amplitude now offers the closest
      correlation with actual pH, UA (r=-0.440 p<<10 (-4)) followed by microfluctuation
      (r=0.224, p<0.001) and frequency (r=0.056, P: n. s.). This pattern is obviously
      due to the retention of all decelerations in the FHR tracings. The 'total sums'
      show less close correlations with pH, UA and BE(oxy) when compared with
      microfluctuation and oscillation amplitude (SumPER vs. pH, UA r=-0.125, p<0.001
      and SumFRQ vs. pH, UA r=-0.154, p<0.001). All five variables under investigation
      show a better correlation with pH, UA when compared with BE(oxy) UA. The WAS
      score computed (mean) for the last 30 min of delivery leads to close correlations
      (p<<10(-4)) with all variables of the foetal ABB: pH, UA r=0.608; BE(oxy)
      r=0.535, pCO(2) r=-0.469 and sO(2) r=0.259. The median WAS score amounts to
      0.176, the mean to 0.174+/-0.023; it is normally distributed in this sample.
      CONCLUSIONS: FHR characteristics in different foetal behavioural states offer the
      opportunity to design a new index, the WAS index, which shows close (p<<10(-4))
      correlations with all variables of the foetal ABB. Thus, the pH value in cord
      blood can be predicted within clinically reasonable limits. The qualitative CTG
      analysis remains untouched.

PMID- 20155662
TI  - Cavernous sinus syndrome secondary to pituitary adenoma: A case report.
AB  - In this case report we demonstrate the intimate association between the sella
      turcica and the cavernous sinus and review the neuroanatomy involved. The
      otolaryngologist should be aware of this association when collaborating with a
      neurosurgeon in pituitary surgery.

PMID- 20155663
TI  - Nasal foreign body as the cause of a subperiosteal orbital abscess in a child.
AB  - We present what to the best of our knowledge is the first reported case of an
      orbital abscess as a result of acute rhinosinusitis caused by obstruction of the
      middle meatus secondary to the impaction of a nasal foreign body in a child. The
      patient, a 5-year-old Hispanic boy, had presented with left periorbital edema,
      eye pain, rhinorrhea, headache, and a fever. The presence of a nasal foreign body
      had been suggested by a finding of a low-density signal in the left anterior
      nasal cavity and middle meatus on computed tomography. Endoscopic drainage of the
      abscess through the involved sinuses revealed that the foreign body was a wad of
      cotton. The cotton was removed, and the patient recovered uneventfully.

PMID- 20155664
TI  - Successful elective surgery in a patient with a positive preoperative cocaine
      toxicology screen.
AB  - A positive result on preoperative cocaine toxicology screening has traditionally
      been a contraindication to immediate nonemergency surgery. We describe a case of
      major but not emergency head and neck surgery on a patient with a massive
      ossifying fibroma whose preoperative toxicology screen was positive for cocaine.
      The surgery was completed without complication, and the patient recovered
      uneventfully. The decision to proceed with surgery was based on the fact that the
      results of urine cocaine screening can remain positive long after the cocaine
      itself has become metabolically inactive, and thus the results may not reflect
      the actual presence of cocaine or the degree of current intoxication. Our
      institution has concluded that elective head and neck surgery may be safely
      performed in carefully selected, hemodynamically stable patients who have tested
      positive for cocaine ingestion provided that they have been closely observed for
      8 hours preoperatively and that they have provided informed consent. Outcome
      studies are needed.

PMID- 20155665
TI  - The pattern of presentation of salivary gland tumors in Africa: A review of
      published reports.
AB  - Salivary glands are the site of a wide variety of histopathologic types of benign
      and malignant tumors. The author reviewed 23 articles from 12 African countries
      published between 1980 and 2004 to examine patterns of salivary gland tumors.
      These neoplasms represent a significant health problem in Africa. The author
      found that patterns of presentation are different from those seen in Western
      countries; for example, African patients are generally younger at presentation.
      Also, there may be a female preponderance in Africa, and Warthin tumor is rare.

PMID- 20155666
TI  - High jugular bulb.

PMID- 20155667
TI  - Dermoid cyst of the parotid gland.
AB  - A dermoid cyst is an ectodermally differentiated form of teratoma. Its occurrence
      in the parotid gland is very rare. Such a presentation must be properly evaluated
      in order to rule out malignancy. We describe the diagnostic evaluation and
      surgical management of a parotid dermoid cyst in an 18-year-old man. We also
      review the embryologic pathogenesis of the tumor and the usefulness of the
      physical examination, preoperative fine-needle aspiration cytology, magnetic
      resonance imaging, and computed tomography in evaluating the extent of the tumor,
      its histologic features, and its cystic characteristics. Finally, we discuss the
      role of surgical management in terms of preserving facial nerve integrity and
      preventing recurrence.

PMID- 20155668
TI  - Necrotizing fasciitis of the head and neck: Report of two cases and literature
      review.
AB  - Necrotizing fasciitis (NF) is a potentially fatal soft-tissue infection
      characterized by rapidly progressive necrosis of subcutaneous tissue and
      superficial fascia. NF of the head and neck is a rare clinical entity, and it
      must be carefully differentiated from less severe conditions. Factors such as
      delayed treatment, inappropriate treatment, host debilitation, and polymicrobial
      infection contribute to the mortality and morbidity of NF. Adequate surgical
      debridement, urgent antibiotic therapy, and supportive measures are the keys to
      decreasing mortality and morbidity. We report 2 new cases and review the
      literature.

PMID- 20155669
TI  - Healthcare for the uninsured: A simpler, cheaper, faster, better solution.

PMID- 20155670
TI  - Treatment of postradiation laryngeal compromise.

PMID- 20155671
TI  - Endoscopic views of bilateral dacryocystorhinostomies.

PMID- 20155672
TI  - Subcutaneous carboxytherapy injection for aesthetic improvement of scars.

PMID- 20155673
TI  - An island of normal mucosa in a sea of Barrett metaplasia.

PMID- 20155674
TI  - Ameloblastoma of the sinonasal tract: A case report.
AB  - Ameloblastomas are locally aggressive gnathic tumors with a high propensity for
      recurrence. Presentation of an ameloblastoma exclusively in the sinonasal tract
      is extremely rare, with few reported cases in the literature. Management involves
      surgical excision and close follow-up. We report a case in which the patient had
      complete unilateral nasal obstruction caused by an ameloblastoma. The tumor was
      completely excised endoscopically, and at the 12-month follow-up, there was no
      evidence of recurrence.

PMID- 20155675
TI  - One-year results: Transantral balloon dilation of the ethmoid infundibulum.
AB  - A prospective, multicenter research study is under way to demonstrate long-term
      improvement in chronic rhinosinusitis symptoms after transantral balloon dilation
      of the ethmoid infundibulum. Trial results from an interim analysis of
      symptomatic status using the Sino-Nasal Outcome Test 20 survey demonstrate
      significant and sustained improvement through post-procedure 1-year follow-up.
      Additionally, these data provide evidence that the symptomatic improvements
      following balloon expansion within the ostiomeatal unit to treat medically
      refractory inflammation of the maxillary sinuses, either alone or with
      concomitant anterior ethmoid disease, are similar.

PMID- 20155676
TI  - Proton pump inhibitor suppression of calcium absorption presenting as respiratory
      distress in a patient with bilateral laryngeal paralysis and hypocalcemia.
AB  - We report an unusual case of hypocalcemia and respiratory distress related to
      acid-suppressive therapy. The patient was a 50-year-old woman with bilateral
      laryngeal paralysis and hypoparythyroidism resulting from a thyroidectomy
      performed more than 30 years previously. She required large doses of calcium
      supplementation to maintain a normal calcium level. Her airway had been
      marginally adequate. A few weeks prior to presentation, she began to experience
      increasing dyspnea. Examination was suggestive of laryngopharyngeal reflux, and
      she was started on a therapeutic trial of esomeprazole 40 mg twice daily. Three
      days later, she presented to the emergency room with airway distress. Laboratory
      studies indicated that the patient had hypocalcemia. The esomeprazole was
      discontinued, and she was treated with intravenous calcium; her symptoms
      resolved. We attribute the airway distress to tetany in synkinetically
      reinnervated laryngeal adductor muscles. We recommend that acid-suppressive
      therapy should be used with caution in patients with hypoparathyroidism or
      hypocalcemia.

PMID- 20155677
TI  - Cervical lymphangioma: An acquired idiopathic presentation in an adult.
AB  - Lymphangioma is an uncommon benign pathology, usually reported in children and
      rarely in adults. In the past, the definitive diagnosis was made intraoperatively
      and was usually an unexpected finding. However, with today's modern imaging
      technologies, such as computed tomography and magnetic resonance imaging, the
      diagnosis can be assumed before intervention, even though the final diagnosis
      still can be reached only via histopathologic examination. Imaging techniques
      also can aid in the precise mapping of the lesion and in defining its boundaries
      with the surrounding vital structures, improving therapeutic success. Various
      therapeutic options are reported in literature, but complete surgical excision is
      still considered the best approach. We report a case of cervical lymphangioma of
      unknown etiology in an 18-year-old man and discuss the presentation, diagnosis,
      and management of this lesion.

PMID- 20155678
TI  - Cervical necrotizing fasciitis: Our experience with 11 cases and our technique
      for surgical debridement.
AB  - We conducted a retrospective review of 11 cases of adult cervical necrotizing
      fasciitis that were treated at our institution over a period of 5-plus years. The
      most common etiology was a dental infection, which was seen in 7 of the 11
      patients (64%). Most cultures were sterile because all of these patients had been
      referred to us after they had already been treated elsewhere with intravenous
      antibiotics and without surgical intervention. Under our management, patients
      spent an average of 21.6 days in the hospital, and they underwent an average of
      1.6 debridements under general anesthesia. Aggressive wound care, broad-spectrum
      antibiotic therapy, and timely surgical intervention resulted in an overall
      survival rate of 91% (10/11), including a 75% survival (3/4) for patients with
      thoracic extension.

PMID- 20155679
TI  - Kimura disease: An unusual cause of head and neck masses. Report of 2 cases.
AB  - Kimura disease is an uncommon chronic, benign, inflammatory condition of unknown
      etiology. It occurs endemically in Asia and sporadically in the West. Because it
      often imitates neoplastic or inflammatory processes of the head and neck,
      otolaryngologists and head and neck surgeons should be aware of its clinical
      presentations. In this article, the author reports 2 cases of Kimura disease-1
      that was characterized by an unusual bilateral presentation and 1 that was
      managed conservatively-and he briefly reviews the literature on this entity.

PMID- 20155680
TI  - Acute suppurative neonatal parotitis: Case report.
AB  - Neonatal suppurative parotitis is very rare. One review of the English-language
      literature spanning 35 years found only 32 cases. Most cases are managed
      conservatively with antibiotic therapy; early antibiotic treatment reduces the
      need for surgery. The predominant organism is Staphylococcus aureus. We report a
      new case of neonatal suppurative parotitis in a 3-week-old boy. The patient was
      diagnosed on the basis of parotid swelling, a purulent exudate from a Stensen
      duct, and the growth of pathogenic bacteria in culture. He responded well to 9
      days of intravenous antibiotic therapy. We also discuss the microbiologic and
      clinical patterns of this disease.

PMID- 20155681
TI  - Bilateral solitary maxillary sinus neurofibroma.
AB  - We present a case of simultaneous bilateral neurofibroma of the maxillary
      sinuses. To the best of our knowledge, this is the first reported case of
      solitary neurofibromas arising from maxillary antra bilaterally and
      independently.

PMID- 20155682
TI  - A critical evaluation of Web sites offering patient information on tinnitus.
AB  - The Internet is a vast information resource for both patients and healthcare
      professionals. However, the quality and content often lack formal scrutiny, so we
      examined the quality of patient information regarding tinnitus on the Internet.
      Using the three most popular search engines (google.com, yahoo.com, and msn.com),
      we found pertinent Web sites using the search term tinnitus. Web sites'
      accountability and authorship were evaluated using previously published criteria.
      The quality of patient information about tinnitus was assessed using a new 10
      point scale, the Tinnitus Information Value (TIV). Statistical analysis was
      performed using the independent sample t-test (p <or= 0.05). An electronic
      database of 90 Web sites was constructed using the first 30 English-language Web
      sites identified by each search engine. After duplicates and sites only
      containing links to other Web sites were eliminated, 39 remained. The mean score
      for accountability was 2.13 on scale of 0 to 7. The mean TIV was 5.0 on a scale
      of 0 to 10. Only 12 sites (30.8%) had their authors clearly identified. Twenty
      two (56.4%) sites were sponsored by commercial interests or represented private
      practices. The mean TIV was significantly higher (p = 0.037) for noncommercial
      (personal, academic institution, or charity) sites (5.88 +/- 2.39 SD) than those
      representing commercial interests (4.32 +/- 2.10 SD). Tinnitus information
      available on the Internet is indeed variable, and care should be taken in
      recommending tinnitus Web sites to patients.

PMID- 20155683
TI  - "Gun-shooting hearing loss": A pilot study.
AB  - Gun-shooting deafness is the common terminology applied to sensorineural hearing
      loss caused by shooting firearms. Many characteristics of gun-shooting hearing
      loss have been proposed, but they have not been defined clearly or established
      conclusively. We studied 37 users of recreational firearms to obtain pilot data
      to help determine if it is true that right-handed gun shooters develop more
      hearing loss in the left ear and vice versa, whether everyone who frequently
      shoots guns develops sensorineural hearing loss, and whether significant hearing
      loss is typically prevented by wearing commercially available ear protectors
      while shooting.

PMID- 20155684
TI  - Ear stapling: a risky and unproven procedure for appetite suppression and weight
      loss.
AB  - In an effort to achieve weight loss, many people are pursuing alternative medical
      interventions. Widely available as a variant of acupuncture, ear stapling (in
      which a surgical staple is placed in the conchal bowl of the ear) is reported by
      practitioners to decrease the appetite and induce weight loss. This practice
      lacks proven efficacy and has a significant risk of infection and deformity. We
      report a series of 3 patients who developed complications from ear stapling and
      present this article to describe the practice so that physicians will be prepared
      when encountering a staple in the ear.

PMID- 20155685
TI  - Bleomycin sclerotherapy in a rare case of adult-onset cervical lymphangioma.
AB  - Cervical lymphangioma in adults is a rare, benign tumor. Traditionally, the most
      accepted treatment has been surgical excision. However, when lymphangioma
      infiltrates vital neurovascular structures, excision is difficult and recurrence
      rates are high. The most common alternate treatment is intralesional injection of
      sclerosing agents, which has resulted in good outcomes in children. However,
      until now, no report of such treatment in adults has been published. We describe
      the case of a 60-year-old woman who presented with two lymphangiomas in the
      cervical area-one in the upper cervical area just below the angle of the mandible
      and the other in the submental area. She was treated with an intralesional
      injection of 1 mg/kg of bleomycin at both sites. Fifteen days later, the
      submental swelling had remitted completely and the other swelling had been
      reduced by 50%; 2 weeks later, a second injection was administered to the
      remaining swelling. At 6 months of follow-up, both lymphangiomas were in complete
      remission.

PMID- 20155686
TI  - Type 2 sulcus vocalis: sulcus vergeture.

PMID- 20155687
TI  - Endoscopic transpterygoid biopsy of a pterygopalatine fossa mass.

PMID- 20155688
TI  - Mastoid pneumocele with secondary pneumatocele causing external auditory canal
      obstruction and the influence of forced nose blowing.
AB  - We present a case involving a 36-year-old man who had a feeling that his right
      ear was obstructed and who had associated conductive hearing loss that was
      exacerbated by nose blowing. On otoscopy, a soft-tissue swelling was seen in the
      posterosuperior aspect of the right external auditory canal. Computed tomography
      revealed the presence of hyperaerated mastoid air cells and an air-containing
      cavity connected with the enlarged mastoid air cells, narrowing the external
      auditory canal. A radiographic diagnosis of a mastoid pneumocele with secondary
      pneumatocele was made. A novel hypothesis is presented, that high nasal pressures
      play an important role in the progressive formation of a pneumocele/pneumatocele
      as a result of air invasion via the eustachian tube. Symptoms disappeared after a
      myringotomy tube was placed. Computed tomography performed 6 months later showed
      an impressive remodeling of the temporal bone.

PMID- 20155689
TI  - Chondrosarcoma of the arytenoid cartilage.
AB  - Chondrosarcoma is the most frequently encountered nonepithelial tumor of the
      larynx. Still, laryngeal chondrosarcoma is a rare disease, accounting for less
      than 1% of all laryngeal neoplasms; only about 600 cases have been reported in
      the world literature. The two most common sites of origin are the cricoid
      cartilage (69% of cases) and the thyroid cartilage (9%); arytenoid cartilage
      origin has been seen in less than 3% of cases. The diagnosis of laryngeal
      chondrosarcoma is easy to miss because of its infrequent occurrence, its indolent
      pattern of growth, and the difficulty in differentiating it histopathologically
      from chondroma. However, suspicion of arytenoid chondrosarcoma may be raised by a
      finding of its characteristic appearance as a smooth, hard, mucosa-covered
      supraglottic mass that is fairly recognizable on indirect laryngoscopy. We report
      a new case of chondrosarcoma of the arytenoid cartilage in a 47-year-old man, and
      we discuss the clinical features, diagnosis, and management of this uncommon
      tumor.

PMID- 20155690
TI  - Longevity: the disposable soma?

PMID- 20155691
TI  - Isolated sphenoid sinusitis presenting as blindness.

PMID- 20155692
TI  - Keratin pearl.

PMID- 20155693
TI  - Intestinal-type sinonasal adenocarcinoma.

PMID- 20155694
TI  - Laryngeal clefts.

PMID- 20155695
TI  - Characterization of ossicular chain vibration at the umbo: implications for a
      middle ear microelectromechanical system design.
AB  - We propose the use of a microelectromechanical system (MEMS) accelerometer as a
      middle ear microphone for future totally implantable cochlear prostheses. The
      MEMS accelerometer would be attached to the umbo to detect and convert the
      natural bone vibration that occurs in response to external sounds into an
      electrical signal that represents the acoustic information. The signal could be
      further processed to stimulate cochlear implant electrodes. To determine the
      feasibility of our proposal, we conducted a study to investigate whether the
      characteristics of umbo vibration along two orthogonal axes-one axis being
      perpendicular to the tympanic membrane and the other axis being parallel to the
      tympanic membrane plane but orthogonal to the long process of the malleus-differ
      significantly enough to compromise the sensing performance of the proposed
      accelerometer should a position misalignment occur during the implant procedure.
      We used laser Doppler vibrometry to measure the displacement of the umbo along
      the two orthogonal axes in 4 cadaveric temporal bones at multiple frequencies
      within the audible spectrum. We found that the peak-to-peak displacement
      frequency response along both axes was nearly flat from 250 Hz to 1 kHz, and it
      gradually rolled off with a slope of approximately -20 dB and -40 dB per decade
      above 1 kHz and 4 kHz, respectively. At each frequency, the displacement
      exhibited a linear function of the input sound level with a slope of 20 dB per
      decade. A comparison of measurements along the two axes indicated a similar
      frequency response, with an average amplitude difference of 20%. The
      characterization data suggest that the performance of a miniature ossicular
      vibration-sensing device attached on the umbo would not be degraded in the event
      of a position misalignment. The data also indicate that a MEMS accelerometer
      needs to achieve a resolution of 35 i g/sqrt[Hz] to detect normal conversation.

PMID- 20155696
TI  - Cerebrospinal fluid rhinorrhea complicating septoplasty: a novel mechanism of
      injury.
AB  - Cerebrospinal fluid (CSF) rhinorrhea after a septoplasty procedure is very rare
      and potentially life-threatening. We present a case of iatrogenic postseptoplasty
      CSF rhinorrhea. To the best of our knowledge, only 2 other cases of CSF
      rhinorrhea complicating septoplasty have previously been reported. However,
      neither resolved in the manner that our case did, when spontaneous cessation of
      CSF rhinorrhea unexpectedly occurred upon removal of intranasal splints. We
      discuss the clinical importance of anatomic variations and potential causative
      mechanisms of CSF rhinorrhea during septoplasty. Our experience with this case
      suggests a mechanism of injury to the cribiform plate during septoplasty that has
      not been described previously.

PMID- 20155697
TI  - Nasal mucosal involvement in Behcet disease: a study of its incidence and
      characteristics in 400 patients.
AB  - Behcet disease is a multisystem vasculitis characterized by mucosal aphthosis,
      primarily in the oral and genital mucosa. Only a few cases of involvement of the
      nasal mucosa have been reported in the literature, and its true prevalence is not
      known. We conducted a cross-sectional study of 400 consecutively presenting
      patients with confirmed Behcet disease (according to classification-tree
      criteria) to determine the incidence of nasal mucosal involvement, to identify
      its particular characteristics, and to determine if there are any statistically
      significant differences in clinical and paraclinical parameters between Behcet
      disease patients with nasal involvement and those without. To the best of our
      knowledge, this is the first systematic evaluation of nasal involvement in
      patients with Behcet disease to be published in the literature. Data analysis was
      performed with Statistical Package for the Social Sciences software (SPSS), and a
      confidence interval (CI) at 95% was calculated for each finding. Involvement of
      the nasal mucosa was seen in 31 of the 400 patients (7.8%; CI: 5.1 to 10.5).
      Among those 31 patients, the most common nasal symptom was dysosmia, which was
      seen in 15 patients (3.8% of the total population; CI: 1.9 to 5.7); other nasal
      symptoms included obstruction in 10 patients (unilateral in 9), ulcers in 2, pain
      in 2, and a burning sensation and discharge in 1 each. No patient reported a
      history of epistaxis or nasal itching. Abnormal signs were present in only 16
      patients (4.0%; CI: 2.1 to 5.9); they included nasal cartilage deformity in 6,
      unilateral nasal obstruction in 4, postnasal discharge in 3, nonaphthous ulcer in
      3, and crusted ulcer in 2 (2 patients each had 2 abnormal signs). No case of
      aphthous ulcer, nasal discharge, nasal scar or deformity, septal perforation, or
      nodular or granulomatous cartilage lesion was found. There were no statistically
      significant differences in clinical and paraclinical disease manifestations
      between those patients who had nasal mucosal involvement and those who did not.

PMID- 20155698
TI  - Laryngeal lipoma associated with diffuse lipomatosis: case report and literature
      review.
AB  - Lipomas are benign mesenchymal tumors that are often found in the head and neck.
      Intrinsic lipomas of the larynx and supraglottic area are rare, as fewer than 115
      cases have been reported in the literature; almost all of these occurred in
      isolation. We report a case of a laryngeal lipoma that was associated with
      diffuse systemic lipomatosis. The tumor was successfully removed via an
      endoscopic laser resection. To the best of our knowledge, this is only the second
      case of laryngeal lipoma associated with lipomatosis to be reported in the
      English-language literature. We also review the literature on head and neck
      lipomas.

PMID- 20155699
TI  - Radiologic findings after successful chemoradiation for nasopharyngeal cancer
      with skull base erosion.
AB  - Nonoperative management is generally accepted as a treatment strategy for
      nasopharyngeal cancer characterized by destruction of the skull base.
      Chemoradiotherapy is considered the standard of care in these cases. We report a
      case in which imaging studies documented the successful treatment of the
      patient's locally extensive nasopharyngeal carcinoma with this nonsurgical
      approach.

PMID- 20155700
TI  - Calcified maxillary cyst secondary to a foreign-body reaction at the site of a
      remote tooth extraction.
AB  - Unilateral sinus disease has a wide differential diagnosis. When a patient has a
      history of maxillary dental work on the same side as the sinusitis, a foreign
      entity introduced during or subsequent to the dental manipulation must be
      considered. We present a case of calcified maxillary cyst that was discovered at
      the site of a remote tooth extraction. Pathologic analysis revealed the presence
      of vegetable matter within the cyst. To the best of our knowledge, no case of a
      maxillary cyst secondary to vegetable matter has been previously reported in the
      literature.

PMID- 20155701
TI  - Pseudophakic eye globe disruption.
AB  - PURPOSE: Scleral rupture due to bulb bursting can result from a heavy contusion.
      Owing to refined surgical techniques and the use of antibiotics and cortisone
      based medication, more conservative concepts have followed. In major ruptures,
      the results were almost always very poor, with atrophy or subatrophy of the eyes.
      METHODS: A 63-year-old man with major left ocular trauma and intraocular lens
      dislocation in the subconjunctival area was referred to the authors for clinical
      and surgical evaluation. RESULTS: Surgery was performed 3 weeks after the trauma
      to allow for improvement in the patient's condition. The reabsorption of a
      palpebral-frontal hematoma, which made bulb exploration almost impossible, was
      fundamental in order to proceed. After 1 year, the best-corrected visual acuity
      was 0.9. In fact, great improvements in surgical techniques in recent years have
      allowed us to consider the problem of major rupture in a new way, both
      technically and from an organizational point of view. CONCLUSIONS: In terms of
      organization, the concept of urgent surgical procedures must be reevaluated,
      because besides traumatic damage, incomplete surgical measures may result. This
      makes all treatment useless, in both barely equipped and highly specialized
      centers.

PMID- 20155702
TI  - Macular congenital hypertrophy of the retinal pigment epithelium: a case report.
AB  - PURPOSE: To describe autofluorescence, microperimetry, and electrophysiology
      findings in a case of macular congenital hypertrophy of the retinal pigment
      epithelium (CHRPE). METHODS: A 58-year-old man was referred to the Department of
      Ophthalmology of the University of Udine for the evaluation of a pigmented
      macular lesion in the right eye. The patient underwent blue-light
      autofluorescence (BL-AF), near-infrared autofluorescence (NIR-AF),
      electrooculogram, full-field electroretinogram and multifocal electroretinogram
      (mfERG), microperimetry, computerized visual field, and optical coherence
      tomography (OCT). RESULTS: BL-AF performed using Heidelberg Retinal Angiograph II
      revealed a homogeneous hypoautofluorescence, surrounded by a hyperautofluorescent
      halo. NIR-AF showed a heterogeneous response combining an increased signal in the
      center of the lesion bordered by a decreased and darker signal. Electrooculogram
      and full-field electroretinogram were normal in both eyes. mfERG revealed only a
      limited area of reduced function in the right eye, which matched to location of
      CHRPE. The segments most functionally altered on mfERG corresponded to the area
      showing an increased signal in the NIR-AF, possibly reflecting the presence of
      increased pigment density within a more viable retinal pigment epithelium-Bruch
      membrane complex. CONCLUSIONS: In essence, macular CHRPE is associated with
      slight defect in retinal sensitivity and outer retinal dysfunction secondary to
      the anatomic changes characteristic of the lesion.

PMID- 20155703
TI  - Acute ophthalmoparesis associated with human parvovirus B19 infection.
AB  - PURPOSE: Parvovirus B19 infection (PVB19) has been linked with a broad spectrum
      of clinical syndromes. In addition to erythema infectiosum and asymptomatic
      infection, other less common manifestations include transient aplastic crisis in
      patients with hemoglobinopathies, pure red cell aplasia and pancytopenia in
      immunocompromised persons, nonimmune hydrops fetalis, chronic arthritis,
      myocarditis, and hepatitis. METHODS: Only 19% of patients had peripheral nervous
      system damage, mainly including brachial plexitis and carpal tunnel syndrome. Two
      cases of cranial nerves palsies have been described in children in the
      literature, including one case of peripheral facial nerve palsy and one case of
      velopalatine hemiparalysis. We report the first case of acute ophthalmoparesis
      associated with PVB19 infection. RESULTS: We present a 40-year-old man with PVB19
      with acute sixth cranial nerve palsy, diagnosed on the basis of serology and
      polymerase chain reaction carried out both on serum and cerebrospinal fluid.
      CONCLUSIONS: Clinicians should be aware of this possible clinical presentation.

PMID- 20155704
TI  - Three-monthly intravitreal bevacizumab injections for neovascular age-related
      macular degeneration: short-term visual acuity results.
AB  - PURPOSE: To evaluate the change in vision after 3 monthly consecutive
      intravitreal injections of 1.25 mg of bevacizumab for neovascular age-related
      macular degeneration (AMD). METHODS: A retrospective analysis of 35 eyes was
      performed. Visual acuity (VA) at initial visit and at each follow-up visit was
      compared. The injection of bevacizumab was performed at 30-day intervals and
      patients were observed for 5 months after the last injection. RESULTS: Of the 35
      eyes, 9 had received previous treatment with photodynamic therapy with or without
      4 mg of intravitreal triamcinolone. VA was measured in Snellen table and
      transformed into logMAR for statistical purposes. Mean age was 76.66 years
      (range, 49-90 years). There were 24 (69%) women and 11 (31%) men. Mean VA at the
      initial visit was 0.92 +/- 0.50. At month 1, mean VA was 0.84 +/- 0.51 and at
      month 2 was 0.74 +/- 0.51. At month 3, mean VA remained 0.74 +/- 0.49. Six and 8
      months after the initial visit, VA was 0.79 +/- 0.49 and 0.77 +/- 0.50,
      respectively. The improvement in VA was statistically significant at month 2 and
      at the end of the follow-up (8 months) compared with the baseline VA.
      CONCLUSIONS: Three consecutive monthly injections of intravitreal bevacizumab to
      treat neovascular AMD is effective in improving VA in the short-term. Longer
      prospective studies should be performed to confirm VA stability after the third
      injection.

PMID- 20155705
TI  - Cataract surgery in the United Kingdom: a postal survey.
AB  - PURPOSE: A postal questionnaire study to evaluate the current practice of
      cataract surgery delivery in the United Kingdom including strategies for
      postoperative review was performed. METHODS: A cataract questionnaire was sent to
      all hospital departments delivering ophthalmic services in the United Kingdom
      based on a list from the Royal College of Ophthalmologists. It included questions
      about the staffing level, number of cases operated on per list, and the different
      strategies employed postoperatively. The results were statistically analyzed.
      RESULTS: A total of 248 questionnaires were sent and 106 (43%) replies were
      received. The mean number of consultant teams was 11 (2-20). The average number
      of cases per list was 6-7 (range 4-9). In 65 hospitals, all patients are reviewed
      postoperatively in the hospital and some consultant teams review patients
      postoperatively in 18 hospitals. In 15 hospitals, patients were seen by the
      community optician. Most hospitals review their patients postoperatively within
      the first 3 weeks with more hospitals seeing them at 2-3 weeks. A wide variety of
      health professionals review the postoperative cases and they include doctors,
      nurses, and opticians (in house and community). CONCLUSIONS: There are varied
      practices for cataract surgery in the United Kingdom including the number of
      cases on the list and postoperative review protocols. There is room for better
      service organization in some hospitals in terms of patient flow and better use of
      medical staff time to improve output.

PMID- 20155706
TI  - Evaluation of the effect of topical cyclosporine A with impression cytology in
      dry eye patients.
AB  - PURPOSE: This study evaluated the efficacy of topical cyclosporine A 0.05%
      treatment with impression cytology in dry eye patients. METHODS: Forty eyes of 40
      patients with dry eye were included. Schirmer tear break-up time, and Ocular
      Surface Disease Index (OSDI) scores and goblet cell densities were noted before
      and after 6 months of topical cyclosporine A treatment. Patients were graded
      clinically and biomicroscopically as follows: grade 1, 12 patients; grade 2, 18;
      and grade 3, 10 patients. RESULTS: Mean age was 57.1 +/- 11.8 (23.0-80.0) years.
      A total of 36 (90%) of the patients were female and 4 (10%) were male. Mean
      Schirmer test value was 3.2 +/- 1.6 (0.0-8.0) mm in the beginning and was 8.4 +/-
      4.3 (1.0-19.0) mm after 6 months of cyclosporine A topical treatment (p = 0.00).
      At the first visit, mean tear break-up time was 4.4 +/- 1.8 (2.0-8.0) seconds. It
      increased to 11.8 +/- 4.8 (2.0-20.0) seconds at the end of the sixth month (p =
      0.00). Mean clinical grading was 1.9 +/- 0.8 (1.0-3.0) and this value regressed
      to 0.8 +/- 1.2 (0.0-3.0) after the treatment (p = 0.00). Mean OSDI score was 30.0
      +/- 11.7 (9.0-50.0) before the treatment and 21.3 +/- 11.0 (4.0-47.0) after the
      treatment (p = 0.00). Mean goblet cell density of all cases was 12.3 +/- 8.7
      before the treatment (2.0-28.0). It increased to 33.0 +/- 25.4 (6-70) after the
      treatment (p = 0.04). CONCLUSIONS: Topical cyclosporine A treatment is effective
      in grade 1 and grade 2 dry eye patients but results are poor in grade 3 patients.

PMID- 20155707
TI  - Phacoemulsification after deep anterior lamellar keratoplasty.
AB  - PURPOSE: To evaluate the results of phacoemulsification and intraocular lens
      implantation after deep anterior lamellar keratoplasty (DALK). METHODS:
      Retrospective, consecutive, noncomparative, single-surgeon series. RESULTS:
      Sixteen eyes of 16 patients were included (mean age: 51 years). Five eyes had
      phacoemulsification because of cataract, and 11 eyes for myopic refractive lens
      exchange. No intraoperative or postoperative complications were noted. Mean
      spherical equivalent (SE) improved from -8.69 D (SD 3.74) to -0.97 D (SD 1.13).
      Mean preoperative defocus equivalent (DE) improved from 10.32 D (SD 4.04) to 2.57
      D (SD 0.92). Mean preoperative best spectacle-corrected visual acuity improved
      from 0.48 logMAR (SD 0.60) to 0.13 D (SD 0.005). Mean postoperative uncorrected
      visual acuity was 0.675 logMAR (SD 0.252). Safety index was 2.33, efficacy index
      was 0.70, and endothelial cell loss was not significant. CONCLUSIONS:
      Phacoemulsification can provide safe and predictable visual rehabilitation for
      cataract and refractive errors resulting after DALK.

PMID- 20155708
TI  - Surgical treatment of esotropia associated with high myopia: unilateral versus
      bilateral surgery.
AB  - PURPOSE: To compare unilateral versus bilateral surgical treatment of esotropia
      associated with high myopia. METHODS: This retrospective study comprised patients
      who underwent surgery for esotropia with high myopia performed by the first
      author (Y.M.) between 2003 and 2008. Surgical results and complications were
      compared between patients who underwent unilateral versus bilateral surgery.
      RESULTS: Nine patients were identified with average age of 44.9 years (range 8-70
      years). All had bilateral high myopia (average -13.35 D, range -9.00 to -17.50 D)
      and esotropia of 20-75 diopters, together with hypotropia in 5 cases. Bilateral
      displacement of the lateral rectus inferiorly and superior rectus medially was
      demonstrated in each patient by computed tomography scan of the orbits and by
      observation during surgery. Five patients underwent bilateral surgery and 4
      underwent unilateral surgery. After an average follow-up of 29 months (range 4-47
      months), 4/5 patients who underwent bilateral myopexy achieved good results with
      postoperative esotropia of less than 8 diopters, as opposed to 2/4 patients who
      underwent unilateral surgery. No complications were noted. CONCLUSIONS: Bilateral
      superior and lateral rectus myopexy is the preferred method of surgical
      correction of esotropia associated with high myopia. Additional unilateral or
      bilateral medial rectus recession is probably not indicated in most cases.
      Patients who prefer unilateral surgery can benefit from unilateral superior and
      lateral rectus myopexy together with medial rectus recession. This unilateral
      approach may yield good results particularly in young patients without markedly
      restricted and tight extraocular muscles.

PMID- 20155710
TI  - Retinopathy of prematurity: screening guidelines need to be reevaluated for
      developing countries.
AB  - PURPOSE: Timely screening of premature babies is an important initial step in the
      management of retinopathy of prematurity (ROP) as earlier treatment results in
      improved visual prognosis. Screening criteria for ROP currently recommended by
      the American Academy of Pediatrics may not be applicable in developing countries.
      The aim of the present study is to find out the incidence of ROP in infants with
      a gestational age (GA) of > or = 32 weeks in Eskisehir, Turkey, to provide
      information to assist in determining screening criteria. METHODS: A total of 96
      infants with a GA of 32-35 weeks who were referred for ROP between January 1,
      2004, and December 31, 2008, were studied. ROP screening, follow-up, and
      appropriate therapies were applied. RESULTS: During ROP screening, there were 42
      of 96 (43.8%) infants with no ROP. A total of 54/96 (56.2%) infants were noted to
      have ROP. Among all infants, 7 (7.3%) had threshold ROP. Two infants with
      threshold disease were born at the 32nd, 2 at the 33rd, and 3 at the 34th week of
      gestation. The mean birthweight was 1857.9 (range 1060-3200) grams. CONCLUSIONS.
      In our study, it was found that more mature infants may also develop threshold
      ROP and require early treatment. After more information is gained and widespread
      screening, screening protocols covering more mature infants can be designed
      especially for developing countries.

PMID- 20155709
TI  - Detecting retinal vigabatrin toxicity in patients with partial symptomatic or
      cryptogenic epilepsy.
AB  - PURPOSE: Detecting retinal vigabatrin toxicity in patients with partial
      symptomatic or cryptogenic epilepsy can be challenging because of preexisting
      visual field defects secondary to a structural abnormality in the brain or lack
      of collaboration. The aim of this study was to measure the retinal nerve fiber
      layer thickness (RNFLT) with optic coherence tomography (OCT), as well as
      contrast sensitivity, color vision, and perimetry, in patients with partial
      symptomatic or cryptogenic epilepsy on vigabatrin, and to determine the efficacy
      of these tests as markers of vigabatrin-related retinal damage in these subgroups
      of epileptic patients. METHODS: The study involved 38 patients with either
      partial symptomatic or cryptogenic epilepsy and 16 healthy individuals comprising
      the control group. At the time of the study, 14 of the patients were using
      vigabatrin, 10 were receiving sodium valproate monotherapy, and 14 were on
      carbamazepine monotherapy. All the participants underwent RNFLT imaging with OCT,
      contrast sensitivity, color discrimination assessment, and perimetry. RESULTS:
      The average 360 degrees RNFLT of the vigabatrin group was significantly lower
      when compared to the other groups. The average RNFLT of all quadrants except the
      temporal one in the vigabatrin group was also significantly reduced. There was no
      difference in the mean deviation, contrast sensitivity, and color discrimination
      between the study groups, but they were all significantly lower than the control
      group. CONCLUSIONS: RNFLT measurement with OCT can efficiently identify
      vigabatrin toxicity in patients with partial symptomatic and cryptogenic
      epilepsy. Perimetry, contrast sensitivity, and color discrimination assessment
      might be inconclusive in these particular subgroups of epileptic patients.

PMID- 20155711
TI  - Keratitis after implantation of intrastromal corneal ring segments (intacs) aided
      by femtosecond laser for keratoconus correction: case report and description of
      the literature.
AB  - PURPOSE: The majority of reported cases of infectious keratitis after
      intrastromal corneal ring segment implantation have been described after
      mechanical implantation of the segments. We present a case of keratitis after
      implantation of intrastromal corneal ring segments (Intacs) aided by femtosecond
      laser for keratoconus correction and review the relevant literature. METHODS: A
      31-year-old woman with keratoconus underwent uneventful sequential implantation
      of intrastromal corneal ring segments (Intacs) aided by femtosecond laser
      performed 6 weeks apart. Two months after surgery in the second eye, she
      complained of red eye, pain, and decreased vision of 2 days' duration. Left eye
      visual acuity was 20/100. RESULTS: Slit-lamp examination of the left eye revealed
      a stromal infiltrate at the lower segment near the incision site. The infiltrate
      progressed despite topical treatment of vancomycin and ceftazidime. Cultures were
      negative. The inferior segment was removed and the inferior channel irrigated
      with antibiotics. One day later significant fibrin and 1-mm hypopyon were
      detected in the anterior chamber Significant improvement was observed after
      adding topical amikacin and amphotericin B. Six months later, a small stromal
      scar is present at the inferior incision site and best-corrected visual acuity is
      20/25. CONCLUSIONS: To our knowledge, this is the second reported case of
      keratitis after implantation of intrastromal corneal ring segments (Intacs) aided
      by femtosecond laser for keratoconus correction. Prompt and adequate treatment is
      essential to prevent irreversible reduction of visual acuity.

PMID- 20155712
TI  - Can the acute-phase reactant proteins be used as cancer biomarkers?
AB  - The association between the acute-phase reactant proteins (APRPs) and cancer has
      long been established. There have been numerous reports correlating altered
      levels of various APRPs with different types of cancers. However, researchers are
      often quick to dismiss the use of these APRPs as potential biomarkers for the
      diagnosis and monitoring of cancer because alterations in APRP concentrations are
      observed in a wide range of diseases. Recent progress in proteomics studies which
      profiled the serum proteins of cancer patients and those of normal individuals
      indicated that the altered APRP expressions were different for distinct types,
      subtypes, and even stages of cancer. Interestingly, these data are in agreement
      with those observed earlier using immunochemical and biochemical assays. In view
      of this compelling association of different patterns of APRPs with various types
      of cancers and in an apparent shift of paradigm, we present in this review some
      indications that APRP fingerprinting may be used as complementary cancer
      biomarkers.

PMID- 20155713
TI  - Human kallikrein 14 (KLK14) expression in salivary gland tumors.
AB  - OBJECTIVE: To analyze the expression of human kallikrein 14 (KLK14) in salivary
      gland tumors. METHODS: A standard immunoperoxidase staining technique was used to
      assess the expression profile of KLK14 in normal salivary glands and tumors
      including pleomorphic adenoma (PA; n=17), adenoid cystic carcinoma (ACC; n=13)
      and mucoepidermoid carcinoma (MEC; n=9). Tumor stage, grade, patient age and
      gender, and site of occurrence were recorded. These clinical parameters were
      correlated with KLK14 levels in malignant tumors. The expression profiles for
      KLK3, 5, 6, 8 and 13 were also retrieved. RESULTS: Normal salivary glands, PA,
      ACC and MEC showed strong expression of KLK14 in ductal and non-ductal cells.
      Both PA and ACC showed higher KLK14 levels than normal glands and MEC tissues.
      There were no statistically significant associations between levels of KLK14 and
      clinical parameters. CONCLUSIONS: The differences in the levels of KLK14 suggest
      that KLKs may aid in the differential diagnosis of salivary gland tumors. The
      coexpression of KLKs suggests their possible involvement in an enzymatic pathway
      activated in salivary gland. KLK14 may be a promising new biomarker in salivary
      gland tumors.

PMID- 20155714
TI  - Analysis of cytokine pattern in exhaled breath condensate of patients with
      squamous cell lung carcinoma.
AB  - Exhaled breath condensate (EBC) analysis is a promising method for investigating
      airway pathology. In this study we compared the cytokine pattern of EBC of
      patients suffering from squamous cell lung carcinoma with that of healthy
      smokers. Breath condensates collected from 8 smoking lung cancer patients before
      receiving any anticancer treatment and 8 smokers without any clinical or
      radiological evidence of pulmonary tumors were used for antibody microarray
      analysis testing 120 cytokines simultaneously. Ninety-eight cytokines on the
      array gave a detectable signal in both groups. Cytokine levels were similar
      across the samples, and none of the cytokines exhibited a significant increase or
      decrease in cancer patients as compared to healthy subjects with similar smoking
      status, lung function, and airway inflammation. The results of this pilot study
      suggest that patients with squamous cell lung carcinoma cannot be distinguished
      from smokers with no pulmonary tumors based on EBC cytokine signals only.

PMID- 20155715
TI  - Proximalization of the arterial inflow (PAI) in patients with dialysis access
      induced ischemic syndrome: first report on long-term clinical results.
AB  - PURPOSE: Proximalization of the arterial inflow (PAI) is a promising technique
      which was introduced several years ago as a treatment option for patients with
      dialysis access-induced ischemic syndrome (DAIIS). In our institutions we have
      been performing PAI since 2003 and have seen positive clinical results. The aim
      of this prospective survey is to present the long-term results of PAI. METHODS:
      Between 2003 and 2008, forty PAI operations were performed in our institutions: 4
      patients had acute pain and sensorimotor dysfunction with no lesions, 33 had
      small acral lesions, and 3 had extended lesions following the creation of
      autogenous fistulas. In 22 cases a heparinized graft was used and in 18 cases a
      regular PTFE-graft. Criteria for successful treeatment of the disease course were
      evaluated by clinical and ultrasound examinations. RESULTS: In 36 cases (90%),
      PAI led to clinical success which was permanent in 33 patients (82%) seen in the
      follow-up period of 9 to 40 months. Primary patency was 62% after 12 months and
      secondary patency was 75% after 18 months. Heparinized grafts led to better
      patency rates. In 3 out of the 4 patients with large acral lesions, graft
      explantation was necessary due to infection or failing success. CONCLUSIONS:
      Based on our experience, clinical long-term results are successful in certain
      patients with DAIIS. The aim for the near future should be a better patency rate
      to minimize the need for reoperations. In cases of extended limb
      necrosis/gangrene results were poor. In such patients primary closure of the
      access must be discussed.

PMID- 20155716
TI  - High brachial artery bifurcation is associated with failure of brachio-cephalic
      autologous arteriovenous fistulae.
AB  - OBJECTIVE: Although European Best Practice Guidelines on vascular access
      recommend universal pre-operative duplex scan in patients receiving brachio
      cephalic (BC) arteriovenous fistulae (AVF), this is not widespread practice.
      Furthermore, cadaveric and angiographic studies suggest that variation in upper
      limb arterial anatomy is common. Our aim was to investigate the prevalence of
      high brachial artery bifurcation (HB) and its impact on BC AVF patency. METHODS:
      A retrospective analysis of consecutive autologous BC AVF created over an 18
      month period (January 2008 to June 2009). Patients with high bifurcations
      identified at duplex scan were compared with a control group who had normal
      bifurcations. All patients were followed up at 1, 6 and 12 weeks post
      operatively. The study endpoint was AVF patency. RESULTS: One hundred and five
      autologous BC AVF procedures were performed in our institution, of which 29
      (27.6%) were identified as having a high brachial bifurcation on pre-operative
      duplex scan. The bifurcation was axillary in six patients and located at the
      proximal, middle and distal third of the humerus in nine, seven and seven
      patients, respectively. The actuarial functional patency rate was 53.2% (standard
      error = 9.6%) in the HB group and 76.2% (standard error = 4.9%) in the control
      group (log-rank test, p=0.027). CONCLUSIONS: These data show that aberrant
      brachial artery anatomy is both common (12%) and a predictor of autologous BC AVF
      failure. These data support the universal use of pre-AVF duplex scanning.

PMID- 20155717
TI  - Maintaining vascular access: the management of hemodialysis arteriovenous grafts.
AB  - For the nephrologist and surgeon, maintaining vascular access is a significant
      challenge in hemodialysis (HD), because the portal is vulnerable to infection,
      stenosis, and thrombus. Vascular access options for HD include the placement of
      arteriovenous (AV) fistulas, AV grafts, and double-lumen, cuffed central vein
      catheters. Catheter use is generally associated with higher rates of infection
      and could compromise the adequacy of HD. Primary AV fistulas, which are generally
      recommended and provide excellent HD access, are not always the ideal choice for
      certain patients, such as the elderly or patients with diabetes mellitus. AV
      grafts allow for a large surface area available for cannulation, and thrombosed
      grafts have longer patency rates after revision than do revised fistulas.
      Although both AV fistulas and AV grafts are vulnerable to thrombosis and/or
      stenosis, surveillance and techniques such as Doppler ultrasound and
      intravascular ultrasound can minimize such complications. In addition,
      pharmacotherapeutic options are being studied to determine whether these
      complications can be prevented. Studies using a variety of pharmacologic agents
      have been conducted to determine whether stenosis and graft thrombosis can be
      prevented and have produced varying results. The use of warfarin can result in
      significant bleeding, but agents such as fish oil and angiotensin-converting
      enzyme inhibitors have shown some effect in increasing the patency in AV grafts
      and fistulas. Additional randomized trials with at least 1 or 2 yrs of follow-up
      are necessary to assess the long-term use of these pharmacotherapies.

PMID- 20155718
TI  - A case of infectious endocarditis-associated crescentic glomerulonephritis with
      intracranial hemorrhage.
AB  - A 55-year-old woman was admitted to our hospital because of fever and renal
      impairment. The patient had undergone a tooth extraction 11 months prior to
      admission. Echocardiography demonstrated vegetation on the mitral valve, and
      Streptococcus mitis was detected on blood culture. Accordingly, infectious
      endocarditis (IE) was diagnosed. Renal biopsy showed crescentic
      glomerulonephritis. Based on the negative staining for immunoglobulins and
      complement components in immunofluorescence study and lack of dense deposits on
      electron microscopy, the renal involvement was considered to be of the pauci
      immune type. Subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) developed
      simultaneously following commencement of antibiotic therapy. The intracranial
      involvement improved by conservative therapy. Antibiotic treatment resulted in
      gradual control of IE infection and improvement of renal function. A repeated
      renal biopsy, performed about 5 months after the first biopsy, showed
      amelioration of glomerular injury and interstitial damage. To our knowledge, our
      case was the second to report simultaneous developments of both SAH and SDH
      secondary to IE. We postulate that the glomerular injury was associated with IE.
      We report here a rare case of IE-associated crescentic glomerulonephritis with
      complications of SAH and SDH.

PMID- 20155719
TI  - Estimate of renal function in oldest old inpatients by MDRD study equation, Mayo
      Clinic equation and creatinine clearance.
AB  - BACKGROUND: Patients older than 85 years are increasingly admitted to hospital
      care settings. Despite this, the clinical employment of equations for estimating
      glomerular filtration rate (GFR) has been scarcely investigated so far in this
      age group. Our study compared 2 commonly employed equations to estimate GFR, as
      well as measured 24-hour creatinine clearance (CrCl), in patients aged >or=85
      years. METHODS: Seventy-three patients consecutively admitted over 4 months to
      our Internal Medicine Department had an accurate 24-hour urinary collection, as
      well as serum and urinary creatinine determinations. Measured CrCl was compared
      with the GFR values estimated by the Modification of Diet in Renal Disease (MDRD)
      Study and Mayo Clinic quadratic (MCQ) equations. RESULTS: GFR values derived by
      MDRD and MCQ equations and CrCl significantly differed from each other in the
      whole sample. CrCl negatively correlated with age (r=-0.389, p<0.001), at
      variance with GFR levels obtained by both the MDRD and the MCQ equations. The 3
      estimates of renal function significantly correlated with each other, these
      correlations persisting after correcting for age, serum albumin and 24-hour
      urinary creatinine. Despite the visual impression of Bland and Altman plots, the
      overall agreement between methods was poor. Moreover, the proportion of patients
      classified by the 3 GFR estimates into each stage of kidney disease as specified
      in the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines
      significantly differed. CONCLUSIONS: In patients older than 85 years, the tested
      equations for estimation of GFR and the measured 24-hour CrCl provide
      significantly different results, so that they may not be used interchangeably in
      clinical practice.

PMID- 20155720
TI  - Association between malnutrition, integrin expression and impaired granulocyte
      adhesion in chronically hemodialyzed patients.
AB  - BACKGROUND: The relationship between malnutrition in hemodialysis (HD) patients
      with a chronic inflammatory condition and the expression levels of leukocyte
      integrins and their adhesiveness to fibronectin was investigated. METHODS:
      Subjective global assessment, albumin and body mass index were used as
      nutritional markers to group malnourished (MP) and eutrophic (EP) patients. C
      reactive protein was used as an inflammation marker. LFA-1, VLA-4 and VLA-5
      expression levels on circulating leukocytes before and after HD were flow
      cytometrically measured; and their adhesiveness, through immobilized fibronectin.
      RESULTS: MPs showed significantly higher VLA-5 expression on granulocytes, when
      compared with healthy individuals (HPs) as controls (13.7% +/- 2.3% vs. 5.0% +/-
      1.1%; p=0.005), particularly after HD (25.8% +/- 4.1%; p<0.001). They also
      presented a significantly lower ability to adhere to fibronectin when compared
      with EPs, before HD (48.8% +/- 1.5% vs. 62.3% +/- 0.7%; p<0.001) and after HD
      (50.6% +/- 1.2% vs. 65.7% +/- 1.4%; p<0.0001). Increased numbers of circulating
      immature neutrophils were observed only in MPs. CONCLUSIONS: Although presenting
      higher VLA-5 expression, malnutrition in HD patients is associated with
      impairment of the adhesive capacity of circulating leukocytes, particularly
      younger neutrophils, which may contribute to the chronic inflammatory status of
      these patients.

PMID- 20155722
TI  - New mutation in female patient with renal variant of Fabry disease and HIV.
AB  - We describe the case of a 27-year-old woman with a family history of Anderson
      Fabry disease (AFD). Urinary sediment presented microhematuria and 0.9 g/24 hours
      proteinuria. The alpha-galactosidase A measurement in fibroblasts showed partial
      deficit of the enzyme, which was compatible with being a carrier of the illness.
      Renal biopsy gave evidence of kidney lesions from Fabry disease. Genetic study
      revealed mutation C52Y or Cys52Tyr, which has not been previously described and
      had also been detected in the father of the patient. During follow-up, the
      presence of hypergammaglobulinemia revealed an underlying HIV disease. She is now
      awaiting enzymatic substitution treatment.

PMID- 20155721
TI  - Screening for chronic kidney disease: which strategy?
AB  - INTRODUCTION: Screening for chronic kidney disease (CKD) has been increasingly
      advocated. However, several criticisms have been levied, and screening programs
      for CKD are not universally accepted. METHODS AND RESULTS: We discuss the
      problems of CKD screening and suggest improvements in the diagnostic and
      therapeutic strategies. Current problems with CKD screening are related to the
      need for both more efficient screening strategies and better screening tests.
      Diabetes mellitus, hypertension and age above 60 years seem to be the most
      important inclusion criteria for a CKD screening program, but only a small and
      variable proportion of CKD cases detected progress to end-stage renal disease
      (ESRD). Recent studies suggest that all stages of CKD should be stratified by the
      presence or absence of albuminuria. This applies particularly to CKD stage 3 in
      which a large proportion of subjects do not progress any quicker than those
      without kidney disease. Reduced kidney function and albuminuria are also strong
      and independent predictors for cardiovascular events. Screening for CKD using
      existing laboratory databases combined with automated management and referral
      recommendations based on the available evidence base seems to be a promising
      strategy for efficient and more adequate handling of the large number of CKD
      patients. CONCLUSION: Screening for CKD in the general population is still not
      recommended. However, high-risk groups like patients with diabetes mellitus or
      hypertension and subjects above age 60 should have their glomerular filtration
      rate estimated and be tested for albuminuria. Better interplay between primary
      and secondary care is needed for successful implementation of CKD clinical
      guidelines in general practice.

PMID- 20155723
TI  - Microscopic or occult hematuria, when reflex testing is not good laboratory
      practice.
AB  - Consensus opinion suggests that hematuria found by dipstick and not confirmed on
      microscopic examination (<2 erythrocytes per high power field) signifies a false
      positive reagent strip test result. Standard practice is to repeat the dipstick
      test several days later and if still positive to confirm by microscopic
      examination. If discordant results are obtained, experts recommend reflex testing
      for urinary myoglobin and hemoglobin concentrations. The question is whether or
      not this approach represents good laboratory practice. These recommendations are
      not evidence based. We conclude that the reference range for red blood cells on
      the reagent strip should be increased to 25x10(6) cells/L for young men, and
      50x10(6) cells/L for the rest of the adult population, ranges consistent with
      flow cytometry reports. Confirmation reflex testing using tests that have
      inferior sensitivity, precision and probably accuracy is not recommended.

PMID- 20155724
TI  - mTOR inhibitor/proliferation signal inhibitors: entering or leaving the field?
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is a highly conserved
      serine/threonine kinase that controls cell growth and metabolism in response to
      nutrients, growth factors, cellular energy and stress, and has pleiotropic
      effects. Its blockade, by mTOR inhibitors (mTOR-Is), such as sirolimus or
      everolimus, leads to antiproliferative effects. METHODS: We have reviewed the
      major studies that deal with the utilization of mTOR-Is after kidney transplant
      and the outcomes. RESULTS: Calcineurin-inhibitor (CNI) avoidance, under the
      umbrella of sirolimus-based immunosuppression in de novo kidney-transplant (KT)
      patients, is associated with worse results compared with those observed in
      patients receiving CNI-based immunosuppression. Conversely, using mTOR-Is in the
      context of CNI minimization and CNI-free protocols is safe and efficient when
      used after 3 months post-transplant. If cyclosporin A (CsA) is used in
      combination with mTOR-I, considerable dose reduction of both drugs is required. A
      better choice may be withdrawal of CsA from this combination after 3-12 months.
      Later withdrawal or conversion to an mTOR-I may not be beneficial. Kidney
      transplant recipients given mTOR-Is have reduced incidence of de novo
      posttransplant malignancies. Posttransplant Kaposi's sarcoma and nonmelanotic
      skin malignancies frequently undergo remission/regression after conversion to
      mTOR-I immunosuppression. The associated side effects of mTOR-Is are numerous and
      may lead to significant drug cessation. CONCLUSION: mTOR-Is could be more widely
      used in kidney transplant patients due to reduced nephrotoxicity and de novo
      cancer compared with CNIs.

PMID- 20155725
TI  - Association between rosiglitazone use and decline in renal function in patients
      with type 2 diabetes mellitus.
AB  - BACKGROUND: Use of thiazolidinediones (TZDs) in treatment of type 2 diabetes
      mellitus (T2DM) has recently become a matter of major controversy regarding their
      cardiovascular and renal safety. The aim of this study is to investigate the
      association between rosiglitazone use and renal function in diabetic patients.
      METHODS: This is a retrospective cohort study conducted on a population of
      patients with T2DM treated at a large public health service organization. All
      patients who received continuous rosiglitazone therapy for at least 1 year were
      included in the study group. For each patient in the study group, control
      patients with T2DM never treated with rosiglitazone were selected from the same
      population and matched for age, sex, HbA1c% and date of study entry. Level of
      renal function was expressed as estimated glomerular filtration rate (eGFR),
      calculated by the simplified Modification of Diet in Renal Disease (MDRD) Study
      equation. RESULTS: In total, 5,666 patients were included in the study: 1,304
      were treated with rosiglitazone, and 4,362 were matched controls. Baseline eGFR
      was similar in both groups (74.6 +/- 22.9 vs. 73.8 +/- 23.3 ml/min per 1.73 m(2),
      respectively; p=0.291). After 5 years of follow-up, eGFR was significantly lower
      in the rosiglitazone-treated group than in control group (67.7 +/- 23.6 vs. 73.8
      +/- 25.2 ml/min per 1.73 m(2), p<0.001). CONCLUSION: The use of rosiglitazone may
      be associated with a decline of renal function in patients with T2DM. Further
      studies are needed to better quantify the risk-benefit trade-offs associated with
      rosiglitazone therapy.

PMID- 20155726
TI  - Glycosaminoglycan treatment in glomerulonephritis? An interesting option to
      investigate.
AB  - Patients with primary and secondary chronic glomerular diseases are at
      significant risk for progression to end-stage renal disease. Unfortunately the
      treatment armamentarium is relatively limited in terms both of available agents
      and of specificity. Experimental evidence supports the idea that heparin-derived
      agents and glycosaminoglycans (GAGs) favorably affect primary and secondary renal
      diseases. While a number of clinical exploratory studies have addressed the
      effect of these agents in microalbuminuric and macroalbuminuric diabetic
      patients, very few have investigated their activity in nondiabetic renal
      conditions. This paper will review the experimental and clinical evidence on the
      use of GAGs in renal disease other than diabetic nephropathy, following the
      reports of experimental findings supporting their use and the possible mechanisms
      involved: anticoagulant and antiproliferative activity, effect on growth factors
      (PDGF, FGF2 and TGF-beta1), inhibition of heparanase, macrophage renal
      infiltration and of the renin-angiotensin system, and decrease in proteinuria.
      Targeting these pathogenic loops with GAG treatment might be revealed to be very
      rewarding from a clinical point of view. Prospective randomized controlled trials
      with large case populations and definite entry criteria are clearly indicated.

PMID- 20155728
TI  - A stopped-flow study of the dual chemiluminescence for the luminol-KIO4-Mn(2+)
      system in strong alkaline solutions.
AB  - A novel phenomenon of dual chemiluminescence (CL) was observed for the KIO4
      luminol-Mn(2+) system in strong alkaline solutions using the stopped-flow
      technique. Scavenging study of the reactive oxygen species (ROS) suggested that
      the two CL peaks originated from different CL pathways precipated by distinct ROS
      (O2(-) and *OH for the first peak, mainly 1O2 for the second peak). Generation of
      these ROS at different time intervals from the reactions involving IO4(-), O2,
      and Mn(2+) and their subsequent reactions with luminol induced the intense CL
      emission. The relative intensity of the two CL peaks can be tuned over a wide
      range by varying the concentrations of Mn(2-), luminol and KIO4. Because of the
      involvement of different ROS in each pathway, the two CL peaks could respond
      quite differently to various substances. Moreover, variation of the intensity
      ratio of the two CL peaks altered the relative proportions of the corresponding
      ROS, thereby changing their responses to a given substance. The dual CL emission
      acts like a pair of tunable probes and it is believed that this CL system has
      great potential in analytical applications.

PMID- 20155727
TI  - Survey of determinants and effects of timing of referral to a nephrologist: the
      patient's point of view.
AB  - INTRODUCTION: We conducted a survey interviewing end-stage renal disease (ESRD)
      patients just after they began chronic dialysis (CD) to describe characteristics
      and factors associated with early (ER) and late referral (LR), and to analyze the
      consequences of timing of referral to a nephrologist. METHODS: We interviewed 673
      patients via telephone starting CD between 2004 and 2006 in Lazio, Italy, to
      collect information about the year before CD. Multiple logistic regression was
      performed to evaluate the factors associated with LR. RESULTS: We found that 22%
      of patients reported being LRs. A lower probability for LR was found for older
      age, family history of renal diseases, abnormal test for renal functions,
      presence of hypertension, married status and awareness of a nephrology outpatient
      center near home. LR patients had a lower frequency of hepatitis B virus (HBV)
      vaccination (14.9% vs. 41.7%), arteriovenous fistula (31.8% vs. 75.6%) and
      information about renal replacement therapy modalities (33.8% vs. 72.6%), and
      they more often started CD in an emergency (85.8% vs. 41.5%). CONCLUSIONS: The
      percentage of self-reported LR was lower than reported in other studies. However,
      many patients started CD in an emergency, with a catheter as first vascular
      access, without vaccination against HBV and without the possibility of choosing
      their dialysis modality. Individual conditions facilitating contact with medical
      care (older age and presence of comorbidities) seem to be associated with a lower
      probability of LR. These findings emphasize the importance of predialysis patient
      training, confirming the important role that information plays in health service
      access, to improve early and long-term dialysis outcomes.

PMID- 20155729
TI  - Analysis of 2-propanol in exhaled breath using in situ enrichment and
      cataluminescence detection.
AB  - We report a simple gaseous sensor for the sensitive detection of trace 2-propanol
      in exhaled breath using in situ enrichment and cataluminescence detection method
      on the surface of nanomaterials. The influences of heating voltage and absorption
      time on the CTL intensity were discussed, respectively. In the selected
      conditions, the linear range of 2-propanol concentration is 60-600 ppbv and the
      detection of limit is 11 ppbv. Moreover, the lifetime and selectivity of the
      sensor were also investigated. It has the potential to diagnostic volatile
      organic compounds in human breath.

PMID- 20155730
TI  - Rapid detergent removal from peptide samples with ethyl acetate for mass
      spectrometry analysis.
AB  - Detergents are required for the extraction of hydrophobic proteins and for the
      maintenance of their solubility in solution. However, the presence of detergents
      in the peptide samples severely suppresses ionization in mass spectrometry (MS)
      analysis and decreases chromatographic resolution in LC-MS. Thus, detergents must
      be removed for sensitive detection of peptides by MS. This unit describes a rapid
      protocol in which ethyl acetate extraction is used to remove octylglucoside from
      protease digests without loss of peptides. This procedure can also be used to
      reduce interference by sodium dodecyl sulfate, Nonidet P-40, or Triton X-100 in
      peptide samples for MS analysis.

PMID- 20155731
TI  - TimeSTAMP tagging of newly synthesized proteins.
AB  - The ability to quantify or visualize newly synthesized proteins has important
      uses in cell biology. For example, a researcher may wish to quantify basal or
      inducible rates of translation of a specific gene of interest, or detect
      subcellular locations of newly synthesized copies of a protein in order to study
      the role of new protein synthesis in the growth of specialized cellular
      structures. In this unit, the TimeSTAMP method for labeling of newly synthesized
      copies of a protein of interest is described. In the TimeSTAMP method, the
      experimenter expresses a protein of interest as a fusion with a cis-acting
      protease and an epitope tag, both of which are removed by default protease
      activity. Addition of a specific protease inhibitor then allows preservation of
      the tag on subsequently synthesized proteins. Finally, the tag is detected by
      immunological methods.

PMID- 20155732
TI  - Trehalose and protein stability.
AB  - The role of osmolytes, and especially trehalose, in stabilizing proteins under
      stress conditions is now a widely accepted fact. The physical and chemical
      properties of trehalose, i.e., low chemical reactivity, nonreducing nature, high
      glass transition temperature, high affinity for water molecules, existence of a
      number of polymorphs, etc., make it uniquely suitable for stabilizing partially
      unfolded protein molecules and inhibiting protein aggregation. This article
      discusses the various adverse situations that protein molecules face, both within
      the cell and outside, leading to their aggregation and inactivation. The use of
      trehalose in stabilizing protein molecules and helping them retain their
      functionally active forms under such conditions is examined. The various theories
      and mechanisms used to explain the protective action of trehalose are briefly
      presented. The experimental tools that can be used to decipher the mechanism of
      aggregation and the role of trehalose are also discussed.

PMID- 20155733
TI  - Displacement chromatography of proteins.
AB  - This unit discusses the important parameters in designing and optimizing a
      separation by ion-exchange displacement chromatography, including preparing the
      sample and choosing a matrix, column, and buffer. Protocols are provided for
      testing a column, determining binding and elution conditions, displacing the
      sample, and cleaning, regenerating, and storing of displacement columns.

PMID- 20155734
TI  - Abnormal protein bands in patients with multiple myeloma after haematopoietic
      stem cell transplantation: does it have a prognostic significance?
AB  - Abnormal protein bands (APB) unrelated to the original monoclonal protein
      occasionally appear in serum immunofixation samples from patients with multiple
      myeloma (MM) following haematopoietic stem cell transplantation (HCT). To
      investigate the significance of APB, medical records and serum immunofixation
      patterns of 53 MM patients, who had undergone HCT (49 autologous and 4
      allogeneic) at the stem cell transplantation unit of Gazi University Faculty of
      Medicine, were reviewed. Patients were staged according to Durie-Salmon and
      International staging systems (ISS) and disease response was determined according
      to European Bone Marrow Transplantation (EBMT) criteria. Fourteen (26.4%) of the
      53 patients developed APBs after HCT. The median time for the appearance and
      duration of APB was 3 (range 1-24) and 5.5 (range 1.5-14) months, respectively.
      Probability of overall survival (OS) at the end of the follow-up was 77 and 61.4%
      in patients with and without APB, respectively (p = 0.334). The median duration
      of follow-up (767 days (range, 220-2905) vs. 726 days (range, 120-1780) p =
      0.545) was not different in patients with and without APB. Probability of
      progression free survival (PFS) at the end of follow-up was 28.8% in patients
      with and 27.7% in patients without APB (p = 0.835). PFS (910 days (range 180
      2905) vs. 730 days (range 90-1765) p = 0.835) was longer in patients with APB,
      though without statistical significance. Thus, the occurrence of APB post
      transplantation is not associated with any adverse long-term consequences and
      does not require treatment modification.

PMID- 20155735
TI  - Vav-1 expression correlates with NFkappaB activation and CD40-mediated cell death
      in diffuse large B-cell lymphoma cell lines.
AB  - Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with a variable
      response to therapy. We have previously shown that DLBCL cell lines differ in
      their susceptibility to CD40-mediated cell death, and that resistance to CD40
      targeted antibodies correlated with increased expression of markers of immature B
      cell and absence of Vav-1 mRNA. We used gene expression profiling to investigate
      the mechanism of CD40 resistance in these cell lines, and found that resistance
      correlated with lack of Vav-1 and inability to activate NFkappaB upon CD40
      ligation. Analysis of tissue microarrays of 213 DLBCL cases revealed that Vav-1
      expression correlated with a higher proliferative index and the presence of the
      post-germinal centre marker Irf-4. Our results suggest that Vav-1 expression may
      be associated with activated B-cell DLBCL origin and higher proliferative
      activity, and indicate Vav-1 as a potential marker to identify tumours likely to
      respond to CD40-targeted therapies.

PMID- 20155737
TI  - Simulation of sirolimus exposures and population variability immediately post
      renal transplantation: importance of the patient's CYP3A5 genotype in tailoring
      treatment.
AB  - The rapid achievement of efficacious exposure to sirolimus (SRL) after renal
      transplantation is crucial. However, there is high unpredictability in the dose
      to exposure relationship. Part of the variation is related to patients
      originating from subpopulations of fast or slow metabolizers via the CYP3A5*1/*3
      genotype. The probability of achieving therapeutic SRL blood concentrations for
      each subpopulation under two equal-intensity increasing-frequency protocols after
      the start of treatment was explored with Monte Carlo simulation. The population
      pharmacokinetic model and inter-patient variability distributions of Djebli et
      al. (DRH2006) were sampled. They developed a base and final model with a genotype
      covariate for CL/F in patients receiving calcineurin inhibitor (CNI)-free therapy
      with SRL, mycophenolate mofetil and corticosteroids. Fast metabolizers
      (expressers) had a CL/F of 28.3 l/h whilst slow metabolizers (non-expressers) had
      a CL/F of 14.1 l/h. Here, in simulation, a standard 10 mg QD SRL was contrasted
      with a higher frequency of 5 mg BID SRL as related to the proportion of next
      dosed patients being within the 15-30 ng/ml trough levels on day 7 after
      transplantation. Near 0% of expressers on either regimen reached or exceeded the
      30 ng/ml trough on day 7. Expressers showed protocol dependence for the chance of
      being within the 15-30 ng/ml range with the 5 mg BID protocol doubling those
      chances. Non-expressers appeared less protocol dependent for the probability of
      being above or below the 15-30 ng/ml range. The ability to determine the genotype
      early on may help to rationalize the initial titration of individual patients
      receiving CNI-free renal transplantation treatment with SRL.

PMID- 20155736
TI  - Development of otolith receptors in Japanese quail.
AB  - This study examined the morphological development of the otolith vestibular
      receptors in quail. Here, we describe epithelial growth, hair cell density,
      stereocilia polarization, and afferent nerve innervation during development. The
      otolith maculae epithelial areas increased exponentially throughout embryonic
      development reaching asymptotic values near posthatch day P7. Increases in hair
      cell density were dependent upon macular location; striolar hair cells developed
      first followed by hair cells in extrastriola regions. Stereocilia polarization
      was initiated early, with defining reversal zones forming at E8. Less than half
      of all immature hair cells observed had nonpolarized internal kinocilia with the
      remaining exhibiting planar polarity. Immunohistochemistry and neural tracing
      techniques were employed to examine the shape and location of the striolar
      regions. Initial innervation of the maculae was by small fibers with terminal
      growth cones at E6, followed by collateral branches with apparent bouton
      terminals at E8. Calyceal terminal formation began at E10; however, no mature
      calyces were observed until E12, when all fibers appeared to be dimorphs. Calyx
      afferents innervating only Type I hair cells did not develop until E14. Finally,
      the topographic organization of afferent macular innervation in the adult quail
      utricle was quantified. Calyx and dimorph afferents were primarily confined to
      the striolar regions, while bouton fibers were located in the extrastriola and
      Type II band. Calyx fibers were the least complex, followed by dimorph units.
      Bouton fibers had large innervation fields, with arborous branches and many
      terminal boutons.

PMID- 20155738
TI  - Achiral and chiral separations using MEKC, polyelectrolyte multilayer coatings,
      and mixed mode separation techniques with molecular micelles.
AB  - Mixed mode (MM) separation using a combination of MEKC and polyelectrolyte
      multilayer (PEM) coatings is herein reported for the separation of achiral and
      chiral analytes. Many analytes are difficult to separate by MEKC and PEM coatings
      alone. Therefore, the implementation of a MM separation provides several
      advantages for overcoming the limitations of these well-established methods. In
      this study, it was observed that achiral separations using MEKC and PEM coatings
      individually resulted in partial resolution of eight very similar aryl ketones
      when the molecular micelle (sodium poly(N-undecanoyl-L-glycinate)) concentration
      was varied from 0.25 to 1.00% w/v and the bilayer number varied from 2 to 4.
      However, when MM separation was introduced, baseline resolution was achieved for
      all eight analytes. In the case of chiral separations, temazepam,
      aminoglutethimide, benzoin, benzoin methyl ether, and coumachlor were separated
      using the three separation techniques. For chiral separations, the chiral
      molecular micelle, sodium poly(N-undecanoyl-L-leucylvalinate), was employed at
      concentrations of 0.25-1.50% w/v for both MEKC and PEM coatings. Overall, the
      results revealed partial separation with MEKC and PEM coatings individually.
      However, MM separation enabled baseline separation of each chiral mixture. The
      separation of achiral and chiral compounds from different compound classes
      demonstrates the versatility of this MM approach.

PMID- 20155739
TI  - Analysis of phenolic xenoestrogens by pressurized CEC with amperometric
      detection.
AB  - A new method, pressurized CEC with end-column amperometric detection using carbon
      paste electrode, has been developed for the separation and determination of five
      phenolic xenoestrogens in chicken eggs and milk powder samples. Efficient
      separation of five analytes was performed by pressurized CEC using a mobile phase
      consisting of 60% v/v ACN and 40% v/v Tris buffer (5 mmol/L, pH 8.0), +6 kV of
      applied voltage and 7.0 MPa of supplementary pressure. Detection limits of 50, 5,
      2, 10 and 20 ng/mL for pentachlorophenol, bisphenol-A, 2,4-dichlorophenol, 4-tert
      octylphenol and 4-nonylphenol, respectively, were achieved using carbon paste
      electrode as working electrode and +0.8 V as detection potential. Matrix solid
      phase dispersion extraction method had been employed during sample preparation
      procedure, and mean recoveries ranged from 79.2 to 102.6% at different
      concentrations of phenolic xenoestrogens for spiked egg and milk powder samples
      were obtained.

PMID- 20155740
TI  - Preparation of open tubular molecule imprinted polymer capillary columns with
      various templates by a generalized procedure and their chiral and non-chiral
      separation performance in CEC.
AB  - A generalized preparation procedure of open tubular (OT) molecule imprinted
      polymer (MIP) columns is proposed for a number of templates with acidic
      functionality such as profen drugs and others. The template (S-enantiomer) was
      mixed with methacrylic acid, ethylene glycol dimethacrylate and 4-styrenesulfonic
      acid, dissolved in a porogen mixture of ACN/2-propanol (9/1), and incubated in a
      pretreated and silanized fused silica capillary by the thermal non-covalent
      polymerization procedure. The whole preparation procedure was exactly the same
      for all the MIP capillaries except for the selection of template. Nevertheless,
      the morphologies of the MIP layers were markedly variant depending upon the
      choice of template. The separation efficiency of each OT-MIP column for chiral
      separation of R- and S-enantiomers was examined and tuned to obtain the best
      separation efficiency by changing the chromatographic parameters such as eluent
      composition and pH. Different optimized conditions were obtained for different OT
      MIP columns. Nevertheless, a unified eluent could be used to obtain still quite
      satisfactory results. Non-chiral separation of the MIP columns were also examined
      in the unified eluent with two sets of test mixtures, that is, a mixture of
      alkylbenzenes and a mixture of small polar solutes. The chiral and non-chiral
      separation of this study resulted in very good separation efficiencies. This work
      is the very first study for the generalization of preparation of OT-MIP columns
      for a number of templates.

PMID- 20155741
TI  - Comparison of C18 silica and multi-walled carbon nanotubes as the adsorbents for
      the solid-phase extraction of Chlorpyrifos and Phosalone in water samples using
      HPLC.
AB  - A comparison between C(18) silica and multi-walled carbon nanotubes (MWCNTs) in
      the extraction of Chlorpyrifos and Phosalone in environmental water samples was
      carried out using HPLC. Parameters affecting the extraction were type and volume
      of elution solvent, pH and flow rate of sample through the adsorbent. The optimum
      conditions obtained by C(18) cartridge for adsorption of these pesticides were 4
      mL dichloromethane as elution solvent, sample pH of 5, flow rate of 1 mL/min, and
      those for MWCNT cartridge were 3 mL dichloromethane, pH of 5 and flow rate of 10
      mL/min, respectively. Optimized mobile phase for separation and determination of
      these compounds by HPLC was methanol/water (80:20 v/v) with pH=5 (adjusted with
      phosphate buffer). Under optimal chromatographic and SPE conditions, LOD, linear
      range and precision (RSD n=8) were 3.03x10(-3), 0.01-5.00 microg/mL and 2.7% for
      Chlorpyrifos and 4.03x10(-4), 0.01-5.00 microg/mL and 2.3% for Phosalone, in
      C(18) cartridge, respectively. These values for MWCNT were 4.02x10(-6), 0.001
      0.500 microg/mL and 1.8% for Chlorpyrifos and 1.02x10(-6), 0.001-0.500 microg/mL
      and 1.5% for Phosalone, respectively.

PMID- 20155742
TI  - Cotinine as a biomarker of tobacco exposure: development of a HPLC method and
      comparison of matrices.
AB  - Tobacco dependence reaches one-third of the world population, and is the second
      leading cause of death around the world. Cotinine, a major metabolite of
      nicotine, is the most appropriate parameter to evaluate tobacco exposure and
      smoking status due to its higher stability and half-life when compared to
      nicotine. The procedure involves liquid-liquid extraction, separation on a RP
      column (Zorbax XDB C(8)), isocratic pump (0.5 mL/min of water-methanol-sodium
      acetate (0.1 M)-ACN (50:15:25:10, v/v/v/v), 1.0 mL of citric acid (0.034 M) and
      5.0 mL of triethylamine for each liter) and HPLC-UV detection (261 nm). The
      analytical procedure proved to be sensitive, selective, precise, accurate and
      linear (r>0.99) in the range of 5-500.0 ng/mL for cotinine. 2-Phenylimidazole was
      used as the internal standard. The LOD was 0.18 ng/mL and the LOQ was 5.0 ng/mL.
      All samples from smoking volunteers were collected simultaneously to establish a
      comparison between serum, plasma, and urine. The urinary cotinine levels were
      normalized by the creatinine and urine density. A significant correlation was
      found (p<0.01) between all matrices. Results indicate that the urine
      normalization by creatinine or density is unnecessary. This method is considered
      reliable for determining cotinine in serum and plasma of smokers and in
      environmental tobacco smoke exposure.

PMID- 20155743
TI  - RP-thin layer chromatographic method for the quantification of three gingerol
      homologs of ultrasonic-assisted fresh rhizome extracts of Zingiber officinale
      collected from North Western Himalayas.
AB  - A rapid and sensitive RP high-performance thin-layer chromatographic (RP-HPTLC)
      methodology was developed and validated for the quantitative estimation of
      gingerols in methanolic extract of fresh ginger rhizome. The samples were
      chromatographed on RP-TLC glass plates pre-coated with RP-18 60F(254) as the
      stationary phase. Linear ascending development was carried out in twin trough
      glass chamber saturated with ternary-solvent system consisting of acetonitrile
      water-formic acid (7:2:1 v/v/v) at room temperature (25+/-2 degrees C) and plates
      were scanned at 500 nm. The system was found to give compact spots for gingerols
      (R(f) values of 6-gingerol 0.73+/-0.04, 8-gingerol 0.59+/-0.08 and 10-gingerol
      0.36+/-0.05). Linearity was found to be in the range of 140-840 ng/spot for 6
      gingerol, 168-1008 ng/spot for 8-gingerol and 136-816 ng/spot for 10-gingerol
      with significantly high value of correlation coefficient. The linear regression
      analysis data for the calibration plots showed linear relationship (r(2)) and
      ranged from 0.9992 to 0.9937 for 6-, 8- and 10-gingerol. The method was used for
      routine analyses and to obtain relative amounts of the gingerols in the fresh
      rhizomes of the ginger cultivated in different locations of Uttarakhand and
      Himachal Pradesh of North Western Himalayas (India).

PMID- 20155744
TI  - Quantification of lamivudine in human plasma by hydrophilic interaction
      chromatography-tandem mass spectrometry.
AB  - A rapid, selective and sensitive method for the determination of lamivudine in
      human plasma was developed using hydrophilic interaction chromatography-MS/MS.
      This method involved protein precipitation with acetonitrile as sample
      preparation procedure. Lamivudine and famotidine (internal standard) were
      analyzed on a Luna hydrophilic interaction chromatography column with the mobile
      phase of acetonitrile/10 mM ammonium formate (95:5, v/v) and detected using
      electrospray ionization mass spectrometry in the selected reaction monitoring
      mode. The standard curve was linear (r(2)=0.9985) over the concentration range of
      50-3000 ng/mL. The lower limit of quantification was 50 ng/mL using 50 microL of
      plasma sample. The coefficient of variation and relative error for intra- and
      inter-assay at four quality control levels were 2.1-7.5 and -4.0 to 3.3%,
      respectively. The absolute and relative matrix effects for lamivudine and
      famotidine were practically absent. The present method was successfully applied
      to the pharmacokinetic study of lamivudine after oral dosing of lamivudine (100
      mg tablet) to male healthy volunteers.

PMID- 20155745
TI  - Recent advances in application of hydrophilic interaction chromatography for
      quantitative bioanalysis.
AB  - Hydrophilic interaction chromatography (HILIC) provides a complementary
      separation mode to RPLC and thus has been gaining increased utilization in LC
      MS/MS based quantitative bioanalysis. It has proven to be a powerful tool for
      separation of polar compounds and has afforded increased selectivity, higher
      sensitivity, and improved efficiency for quantitation of drug and their
      metabolites in complex biological matrices. Practical knowledge has been gained
      for some of the challenges with HILIC applications and effective remedies have
      been adopted to overcome these challenges. Due to its orthogonality to RPLC,
      HILIC has been coupled with RP sample preparation or separation techniques,
      either off-line or on-line to achieve better assay selectivity. The low back
      pressure with HILIC enables fast separations under higher flow rates. Small
      particle columns can be operated under HILIC conditions with regular system back
      pressure, eliminating the requirement for ultra-high-pressure liquid
      chromatographic systems. Matrix effects under HILIC have also been systematically
      investigated. Effective approaches to reduce or eliminate matrix effects have
      included optimizing sample preparation, modifying chromatographic conditions,
      and/or using valve-switching techniques. Finally, the utilization of HILIC is not
      limited to quantitation of polar drugs and their metabolites, but extended to
      quantitation of relatively non-polar compounds, peptides and biomarkers.

PMID- 20155746
TI  - Determination of aminoglycoside and macrolide antibiotics in meat by pressurized
      liquid extraction and LC-ESI-MS.
AB  - A simple method for the simultaneous determination of dihydrostreptomycin,
      spectinomycin, spiramycin, streptomycin, tilmicosin, and tylosin in meat has been
      developed using pressurized liquid extraction and LC-triple quadrupole MS (LC-ESI
      MS/MS). The pressurized liquid extraction operational parameters were optimized
      and no protein precipitating and fat removing steps were required. A gradient
      HPLC separation was developed with ion-pair mobile phases consisting of aqueous 1
      mM heptafluorobutyric acid water and methanol. Protonated molecules were used as
      precursor ions for CID. Data acquisition under MS/MS was achieved by applying
      multiple reaction monitoring of three fragment ion transitions to provide a high
      degree of sensitivity and specificity. Dirithromycin and sisomycin were selected
      as internal standards. A validation study was conducted for these antibiotics in
      poultry meat samples. All selected compounds could be detected (monitoring ions
      by multiple reaction monitoring) in meat samples at amounts below the regulatory
      level of concern. Using the internal standards, pressurized liquid extraction
      recovery rates were from 70 to 96% (RSD 12-25%). LC-ESI-MS/MS method detection
      limits of the selected antibiotics were 1-6 microg/kg. Good method
      reproducibility was found by intra- and inter-day precisions at maximum residue
      level, yielding the RSDs less than 15 and 16%, respectively.

PMID- 20155747
TI  - Development and validation of a method based on a QuEChERS procedure and heart
      cutting GC-MS for determination of five mycotoxins in cereal products.
AB  - A new analytical method for the rapid and simultaneous determination of five
      mycotoxins (zearelenone, deoxynivalenol, Fusarenon X, 15-acetyldeoxynivalenol and
      nivalenol) in breakfast cereals and flours by heart-cutting GC-MS has been
      developed and validated. Extraction was performed with MeCN, applying a modified
      QuEChERS (QUick, Easy, CHeap, Effective, Rugged and Safe) procedure, and the
      extracts were analyzed after a silylation of the analytes under study. Careful
      optimization of the parameters of Deans Switch device and GC-MS was achieved in
      order to attain a fast separation in SIM mode, allowing a total run time of only
      8 min. Acceptable recoveries for all mycotoxins at two different spiking levels
      (20 and 100 microg/kg) were achieved with good repeatability (from 9 to 21%). LOD
      ranged from 2 to 15 microg/kg and LOQ ranged from 5 to 50 microg/kg, which were
      lower than the maximum limit legal established by the European Union (EU). The
      method developed was applied to commercial breakfast cereals and flours; among
      the mycotoxins studied, deoxynivalenol and zearalenone were the most predominant.

PMID- 20155748
TI  - Lactic acid quantitation in hand dishwashing liquid using an HILIC-UV
      methodology.
AB  - Different hydrophilic interaction chromatography (HILIC) columns were screened
      for lactic acid separation in hand dishwashing liquid products and the influence
      of mobile phase strength, buffer concentration and column temperature on the
      retention of lactic acid on a Zorbax NH(2) column was investigated. An isocratic
      HILIC method for the quantitation of lactic acid in hand dishwashing liquid
      products was developed. The mobile phase consists of 70% methanol and 30% 20 mM
      sodium phosphate buffer (v/v) at pH 2.5. The HILIC stationary phase is Zorbax
      NH(2), 250x4.6 with a 5 microm particle size. Detection was carried out using a
      variable wavelength UV-VIS detector at 226 nm. The linear range and percent
      recovery for lactic acid in the products were 44.68-1206.39 microg/mL and 100.3%,
      respectively. This paper provides an optimized HILIC methodology for the analysis
      of an acidic polar analyte (lactic acid) on a basic stationary phase. The
      proposed method can be used for the routine analysis of lactic acid.

PMID- 20155749
TI  - Comparison of HPLC and CZE methods for analysis of DOTA-like esters--reaction
      intermediates in synthesis of magnetic resonance contrast agents.
AB  - RP-HPLC and non-aqueous CZE methods were evaluated for qualitative and
      quantitative analysis of esterified macrocyclic compounds of the DOTA family
      (DOTA=1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid). This group of
      compounds represents important reaction intermediates in synthesis of magnetic
      resonance contrast agents. Calibration curves in the concentration range from 1.0
      x 10(-5) to 1.0 x 10(-3) mol/L were plotted and the experimental data were
      critically compared in terms of their repeatability, linearity, LOD and LOQ. The
      optimized methods were successfully applied to the analysis of a real reaction
      mixture without any further pretreatment.

PMID- 20155750
TI  - Focusing of anionic micelles using sample-induced transient isotachophoresis:
      computer simulation and experimental verification in MEKC.
AB  - The specific phenomenon of high-salt micelle focusing used as a preconcentration
      method for uncharged solutes in MEKC has been interpreted in terms of
      complementary transient isotachophoresis (tITP) process. High matrix chloride can
      focus anionic SDS micelles not only due to a field-enhanced effect but also by
      creating the tITP state in which chloride acts as a leading ion. The latter
      micelle-enrichment event was simulated by SIMUL software in order to understand
      tITP conditions under which micelle stacking can be expected to occur.
      Specifically, effects of chloride matrix concentration and the nature of BGE co
      ion, performing a role of terminating ion, were explored. A greater extent of
      micelle stacking was observed at a higher chloride concentration in borate than
      in phosphate buffer system. This proof-of-principle simulation result was
      confirmed in real experiments using metal-based chemotherapeutic drugs. It was
      concluded that analyte enrichment requires prolonged interaction with the
      micelle, which is feasible at a proper ratio between sample matrix and BGE co-ion
      concentrations.

PMID- 20155751
TI  - Single-pump bi-dimensional LC applied to the characterization of derivatized
      fatty alcohol ethoxylates.
AB  - A column selection valve and a 6-port 2-position injection valve were combined to
      implement bi-dimensional LC in a system driven by a single pump. The system was
      applied to the separation of linear fatty alcohol ethoxylates with 12-18 carbon
      atoms in the hydrocarbon moiety, previous derivatization with diphenic anhydride.
      Separation on the first separation dimension (C(1)) was carried out with a propyl
      diol column and an acetonitrile/aqueous ammonium acetate gradient. Fatty alcohol
      ethoxylate hydrocarbon series (oligomers with the same number of carbon atoms in
      the alkyl chain but differing in the number of ethylene oxide units) were
      resolved without distinguishing the oligomers within the series. Selected
      segments of the eluate of C(1) were transferred to the second column (C(2)),
      where the successive oligomers within the isolated series were resolved by using
      either an octyl-silica or a pentafluoro-phenyl-propyl column and an
      acetonitrile/water gradient. Flow stopping at C(1) during system re-conditioning
      and elution along the second dimension did not produce any noticeable band
      broadening. Overlapping of the non-ethoxylated and mono-ethoxylated oligomers
      with other oligomers within the series was avoided by eluting the pentafluoro
      phenyl-propyl column at low temperatures (3 degrees C).

PMID- 20155752
TI  - Determination of multicomponent contents in Calculus bovis by ultra-performance
      liquid chromatography-evaporative light scattering detection and its application
      for quality control.
AB  - A fast ultra-performance liquid chromatography-evaporative light scattering
      detection (UPLC-ELSD) method was established for simultaneous quantification of
      seven components in natural Calculus bovis (C. bovis) and its substitutes or
      spurious breeds. On a Waters Acquity UPLC BEH C(18) column, seven analytes were
      efficiently separated using 0.2% aqueous formic acid-acetonitrile as the mobile
      phase in a gradient program. The evaporator tube temperature of ELSD was set at
      100 degrees C with the nebulizing gas flow-rate of 1.9 L/min. The results showed
      that this established UPLC-ELSD method was validated to be sensitive, precise and
      accurate with the LODs of seven analytes at 2-11 ng, and the overall intra-day
      and inter-day variations less than 3.0%. The recovery of the method was in the
      range of 97.8-101.6%, with RSD less than 3.0%. Further results of PCA on the
      contents of seven investigated analytes suggested that compounds of cholic acid,
      deoxycholic acid and chenodeoxycholic acid or cholesterol should be added as
      chemical markers to UPLC analysis of C. bovis samples for quality control and to
      discriminate natural C. bovis sample and its substitutes or some spurious breeds,
      then normalize the use of natural C. bovis and ensure its clinical efficacy.

PMID- 20155753
TI  - Polysaccharide-blend multilayers containing hyaluronan and heparin as a delivery
      system for rhBMP-2.
AB  - It is shown that blend multilayers of hyaluronan (HA) and heparin (HEP) as
      polyanions and poly(L-lysine) (PLL) as a polycation can be used to prepare films
      with different thicknesses and chemical compositions. The amounts of recombinant
      human BMP-2 (rhBMP-2) loaded and the fraction initially released from the films
      depend on the film's chemical composition. The amounts of rhBMP-2 loaded in the
      films are much higher for HA mass fractions of more than 0.4. The bioactivity of
      the rhBMP-2-loaded films is investigated on C2C12 myoblasts, which differentiates
      into osteoblasts in contact with the films. The alkaline phosphatase expression
      for cells grown on nanoblend films of various compositions falls over a unique
      curve. This suggests that the cells "sensing" the rhBMP-2 are not influenced by
      the film's chemistry. The rhBMP-2 can sustain at least three successive culture
      sequences while remaining bioactive, thus confirming the important and protective
      effect of rhBMP-2. Altogether, these results indicate that crosslinked PLL/HA
      films have superior properties for the incorporation of rhBMP-2 and on its long
      lasting bioactivity.

PMID- 20155754
TI  - A gas chromatography/pyrolysis/isotope ratio mass spectrometry system for high
      precision deltaD measurements of atmospheric methane extracted from ice cores.
AB  - Air enclosures in polar ice cores represent the only direct paleoatmospheric
      archive. Analysis of the entrapped air provides clues to the climate system of
      the past in decadal to centennial resolution. A wealth of information has been
      gained from measurements of concentrations of greenhouse gases; however, little
      is known about their isotopic composition. In particular, stable isotopologues
      (deltaD and delta(13)C) of methane (CH(4)) record valuable information on its
      global cycle as the different sources exhibit distinct carbon and hydrogen
      isotopic composition. However, CH(4) isotope analysis is limited by the large
      sample size required and the demanding analysis as high precision is required.
      Here we present a highly automated, high-precision online gas
      chromatography/pyrolysis/isotope ratio monitoring mass spectrometry (GC/P/irmMS)
      technique for the analysis of deltaD(CH(4)). It includes gas extraction from ice,
      preconcentration, gas chromatographic separation and pyrolysis of CH(4) from
      roughly 500 g of ice with CH(4) concentrations as low as 350 ppbv. Ice samples
      with approximately 40 mL air and only approximately 1 nmol CH(4) can be measured
      with a precision of 3.4 per thousand. The precision for 65 mL air samples with
      recent atmospheric concentration is 1.5 per thousand. The CH(4) concentration can
      be obtained along with isotope data which is crucial for reporting ice core data
      on matched time scales and enables us to detect flaws in the measurement
      procedure. Custom-made script-based processing of MS raw and peak data enhance
      the system's performance with respect to stability, peak size dependency, hence
      precision and accuracy and last but not least time requirement.

PMID- 20155755
TI  - A retrospective study by oligonucleotide array-CGH analysis in 50 fetuses with
      multiple malformations.
AB  - OBJECTIVE: To retrospectively define the frequency and the nature of
      submicroscopic chromosomal imbalances among fetuses with multiple congenital
      anomalies (MCA). METHODS: We used oligonucleotide arrays to perform comparative
      genomic hybridization after termination of pregnancy in 50 polymalformated
      fetuses with a normal karyotype. These fetuses presented with at least three
      significant malformations (42 cases) or a severe brain anomaly (eight cases).
      RESULTS: We identified a deleterious copy number variation (CNV) in five fetuses
      (10%). De novo genomic imbalances identified in this study consisted of a 6qter
      deletion in a fetus with brain and renal malformations, a mosaicism for a 8p
      tetrasomy in a fetus with agenesis of corpus callosum, growth retardation, mild
      facial dysmorphic features, and vertebral anomalies, a 17p13.3 deletion in a
      fetus with a complex brain malformation, and a partial 11p trisomy in a fetus
      with severe growth retardation and oligoamnios. In one case, we identified a
      partial 17q trisomy resulting from malsegregation of a cryptic-balanced
      translocation. CONCLUSIONS: This study shows that array comparative genomic
      hybridization (aCGH) is particularly effective for identifying the molecular
      basis of the disease phenotype in fetuses with multiple anomalies. Our study
      should help to define clinical relevant regions that would need to be included in
      targeted arrays designed for prenatal testing.

PMID- 20155756
TI  - De novo sequencing of two new cyclic theta-defensins from baboon (Papio
      hamadryas) leukocytes by matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Two cyclic theta-defensin peptides were isolated from leukocytes of the hamadryas
      baboon, Papio hamadryas, and purified to homogeneity by gel electrophoresis and
      reversed-phase high-performance liquid chromatography. Both peptides had high in
      vitro activity against Escherichia coli, Listeria monocytogenes, methicillin
      resistant Staphylococcus aureus (MRSA) and Candida albicans. Here, we report
      their de novo sequencing by matrix-assisted laser desorption/ionization tandem
      time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). This was accomplished by
      combining conventional enzymatic digestion with N-terminal derivatization by 2
      sulfobenzoic acid cyclic anhydride (SACA) or 4-sulfophenylisothiocyanate (SPITC)
      to facilitate the interpretation of fragment ion spectra. In addition to the two
      cyclic theta-defensins (PhTDs) we also sequenced a novel Papio hamadryas alpha
      defensin, PhD-4, which showed high sequence homology to rhesus alpha-defensin
      RMAD-1 and human alpha-defensin HNP-1.

PMID- 20155758
TI  - Method for improved secondary ion yields in cluster secondary ion mass
      spectrometry.
AB  - A method to increase useful yields of organic molecules is investigated by
      cluster secondary ion mass spectrometry (SIMS). Glycerol drops were deposited
      onto various inkjet-printed arrays and the organic molecules in the film were
      rapidly incorporated into the drop. The resulting glycerol/analyte drops were
      then probed with fullerene primary ions under dynamic SIMS conditions. High
      primary ion beam currents were shown to aid in the mixing of the glycerol drop,
      thus replenishing the probed area and sustaining high secondary ion yields.
      Integrated secondary ion signals for tetrabutylammonium iodide and cocaine in the
      glycerol drops were enhanced by more than a factor of 100 compared with an
      analogous area on the surface, and a factor of 1000 over the lifetime of the
      glycerol drop. Once the analyte of interest is incorporated into the glycerol
      microdrop, the solution chemistry can be tailored for enhanced secondary ion
      yields, with examples shown for cyclotrimethylenetrinitramine (RDX) chloride
      adduct formation. In addition, depositing localized glycerol drops may enhance
      analyte secondary ion count rates to high enough levels to allow for site
      specific chemical maps of molecules in complex matrices such as biological
      tissues.

PMID- 20155759
TI  - Formation of H3O+ from alcohols and ethers induced by intense laser fields.
AB  - The processes of H(3)O(+) production from alcohols (ethanol, 2-propanol, 1
      propanol, 2-butanol) and ethers (diethyl ether and ethyl methyl ether), and their
      deuterium-substituted species, by intense laser fields (800 nm, 100 fs,
      approximately 1 x 10(14) W/cm) were investigated through time-of-flight (TOF)
      mass spectrometry. H(3)O(+) formation was observed for all these compounds except
      for ethyl methyl ether. From the analysis of TOF signals of H((3-n))D(n)O(+) (n =
      0, 1, 2, and 3) that have expanding tails with increasing flight time, it has
      been confirmed that the reaction proceeds through metastable dissociation from
      the intermediate species C(2)H((5-m))D(m)O(+)(m = 0-5). The common shape of the
      H((3-n))D(n)O(+) signal profiles contains two major distributions in the time
      constant, i.e., fast and slow components of <50 ns and approximately 500 ns,
      respectively. The H((3-n))D(n)O(+) branching ratio is interpreted to be the
      result of complete scrambling of four hydrogen atoms at the C-C site in C(2)H(4)
      OH(+), and partial exchange (18-38%) of a hydrogen atom in the OH group with four
      other hydrogen atoms within 1 ns prior to H((3-n))D(n)O(+) production. Ab initio
      calculations for the isomers and transition states of C(2)H(5)O(+) were also
      performed, and the observed H((3-n))D(n)O(+) production mechanism has been
      discussed. In addition, a stable isomer having a complex structure and two
      isomerization pathways were discovered to contribute to the H(3)O(+) formation
      process.

PMID- 20155760
TI  - Comprehensive characterization of marine dissolved organic matter by Fourier
      transform ion cyclotron resonance mass spectrometry with electrospray and
      atmospheric pressure photoionization.
AB  - We compare the ultrahigh resolution 9.4 T Fourier transform ion cyclotron
      resonance (FT-ICR) mass spectra of marine dissolved organic matter (DOM) isolated
      from two sites in the Weddell Sea (Antarctica) obtained by complementary
      electrospray ionization (ESI) and atmospheric pressure photoionization (APPI).
      Ions produced by APPI extend to higher carbon unsaturation than those produced by
      ESI, indicated by higher double-bond equivalents (rings plus double bonds) minus
      oxygen (DBE-O) values, whereas ESI-generated ions are more oxygenated. Moreover,
      many sulfur-containing compounds were efficiently ionized by ESI but not detected
      by APPI. Because the mass spectra obtained by ESI and APPI are significantly
      different, both are necessary to obtain a more complete description of the
      molecular composition of marine DOM.

PMID- 20155761
TI  - Bodily variability of zinc natural isotope abundances in sheep.
AB  - Evidence is growing that the range of zinc stable isotope compositions,
      represented by the deviation of (66)Zn in permil units relative to a standard and
      expressed as delta(66)Zn, is larger in organic matter than in inorganic material.
      This study reports the variations of delta(66)Zn in various organs of sheep
      raised on a controlled diet. Zinc was purified by anion-exchange chromatography.
      The Zn concentrations and Zn stable isotope compositions were determined by
      quadrupole inductively coupled plasma mass spectrometry and multi-collector
      inductively coupled plasma mass spectrometry, respectively. The data show that
      delta(66)Zn variability exceeds 1 per thousand, with bone, muscle, serum and
      urine enriched in the heavy isotopes, and feces, red blood cells, kidney and
      liver enriched in light isotopes, all relative to the diet value. The (66)Zn
      enrichment of the circulating serum reservoir is likely to take place in the
      digestive tract, probably through the preferential binding of lighter isotopes
      with phytic acid, which is known to control the uptake of metallic elements. Mass
      balance calculations suggest that the (66)Zn depletion between diet and feces,
      which is not balanced by any other outward flux, leads to a secular isotopic
      drift in serum. A simple time-dependent two-box model, involving the gastro
      intestinal tract on the one hand and the muscle and bone on the other, predicts
      that the maximum (66)Zn enrichment, which equals the difference in delta(66)Zn
      between diet and bulk (approximately 0.25 per thousand), is reached after about
      ten years. Therefore, a better understanding of the variations of natural
      abundance of Zn isotopes in animals and humans will probably bring new
      perspectives for the assessment of their Zn status.

PMID- 20155762
TI  - Systematic screening and characterization of novel bufadienolides from toad skin
      using ultra-performance liquid chromatography/electrospray ionization quadrupole
      time-of-flight mass spectrometry.
AB  - During the discovery process of novel compounds, it is of significant importance
      to differentiate novel from known compounds in crude extracts before starting the
      time-consuming process of purification. Bufadienolides are the main active
      components of the skin of the toad Bufo bufo gargarizans Cantor (toad skin), an
      important traditional Chinese medicine. The fragmentation behavior and mass
      spectra profiles of bufadienolides standards were investigated using ultra
      performance liquid chromatography/electrospray ionization quadrupole time-of
      flight mass spectrometry (UPLC/ESI-Q-TOFMS). Several fragmentation rules were
      summarized and applied to characterize novel and known bufadienolides in toad
      skin. Characteristic substituent groups could be identified by both diagnostic
      ions and their relative abundance. Bufadienolide stereoisomers could be
      differentiated from positional isomers by comparing fragment abundance profiles.
      This was used to characterize new stereoisomers for known bufadienolides. A total
      of 39 bufadienolides were screened out using a systematic method developed in our
      laboratory. In addition to 19 known bufadienolides, 20 putative novel compounds,
      including 8 stereoisomers, were characterized. UPLC/Q-TOFMS was demonstrated to
      be a powerful tool for the characterization of low-abundance bufadienolides in
      complex samples. This study provides guidelines for the targeted isolation of
      novel bufadienolides from natural products.

PMID- 20155763
TI  - Liquid chromatographic/electrospray ionization mass spectrometric identification
      of the oxidation end-products of trans-resveratrol in aqueous solutions.
AB  - trans-Resveratrol (3,5,4'-trihydroxystilbene) is a natural polyphenolic compound
      that exhibits antioxidant properties. Our study aimed at studying the HO*-induced
      oxidation of resveratrol (100 micromol.L(-1)) in aerated aqueous solutions. Gamma
      radiolysis of water was used to generate HO*/O(2)(*-) free radicals (I = 10
      Gy.min(-1), dose = 400 Gy). Oxidation products were identified by direct infusion
      mass spectrometry and high-performance liquid chromatography/mass spectrometry.
      For each product, structural elucidation was based on simple mass spectra,
      fragmentation spectra and deuterium/hydrogen exchange spectra; the comparison
      with mass spectra of synthetic products provided valuable information allowing
      the complete identification of the oxidation products. Four products resulting
      from the direct attack of HO* radicals towards resveratrol were identified
      respectively as piceatannol (trans-3,5,3',4'-tetrahydroxystilbene), 3,5
      dihydroxybenzoic acid, 3,5-dihydroxybenzaldehyde and 4-hydroxybenzaldehyde.

PMID- 20155764
TI  - Total synthesis of myrtucommulone A.

PMID- 20155765
TI  - A unique Pd4 platform with CH3 and mu-CH2 groups and its C-C coupling reaction
      with simple olefins.

PMID- 20155766
TI  - DNA analysis by dynamic chemistry.

PMID- 20155767
TI  - Targeted lipoCEST contrast agents for magnetic resonance imaging: alignment of
      aspherical liposomes on a capillary surface.

PMID- 20155768
TI  - Electron hopping over 100 A along an alpha helix.

PMID- 20155769
TI  - Octamethylbicyclo[3.2.1]octadienes from the rhizobacterium Serratia odorifera.

PMID- 20155771
TI  - Charged-assisted supramolecular catalysis.

PMID- 20155770
TI  - The sex pheromone of the wasp spider Argiope bruennichi.

PMID- 20155772
TI  - Evolution of O2 in a seven-coordinate Ru(IV) dimer complex with a [HOHOH]-
      bridge: a computational study.

PMID- 20155773
TI  - Self-assembled TiO2 nanocrystal clusters for selective enrichment of intact
      phosphorylated proteins.

PMID- 20155774
TI  - Gold-catalyzed halogenation of aromatics by N-halosuccinimides.

PMID- 20155776
TI  - Characterisation of oxazepam degradation products by high-performance liquid
      chromatography/electrospray ionisation mass spectrometry and electrospray
      ionisation quadrupole time-of-flight tandem mass spectrometry.
AB  - Oxazepam has been subjected to controlled degradation at 100 degrees C for 3 h in
      0.5 M HCl and 0.5 M NaOH. Following neutralisation of the degradation mixture and
      removal of salts by solid-phase extraction (SPE), isocratic high-performance
      liquid chromatography/mass spectrometry (HPLC/MS) using water/methanol (25:75
      v/v) as the mobile phase was carried out using a flow diverter to collect
      fractions prior to their characterisation by electrospray ionisation multi-stage
      mass spectrometry (ESI-MS(n)) and proposal of the corresponding fragmentation
      patterns. The elemental compositions of the degradation products and their MS
      fragments were evaluated using electrospray ionisation quadrupole time-of-flight
      tandem mass spectrometry (ESI-QTOF-MS/MS) which was then used to support the
      proposed fragmentation patterns.

PMID- 20155777
TI  - Which controls the depolymerization of cellulose in ionic liquids: the solid acid
      catalyst or cellulose?
AB  - Cellulose is a renewable and widely available feedstock. It is a biopolymer that
      is typically found in wood, straw, grass, municipal solid waste, and crop
      residues. Its use as raw material for biofuel production opens up the possibility
      of sustainable biorefinery schemes that do not compete with food supply. Tapping
      into this feedstock for the production of biofuels and chemicals requires--as the
      first-step--its depolymerization or its hydrolysis into intermediates that are
      more susceptible to chemical and/or biological transformations. We have shown
      earlier that solid acids selectively catalyze the depolymerization of cellulose
      solubilized in 1-butyl-3-methylimidazolium chloride (BMIMCl) at 100 degrees C.
      Here, we address the factors responsible for the control of this reaction. Both
      cellulose and solid acid catalysts have distinct and important roles in the
      process. Describing the depolymerization of cellulose by the equivalent number of
      scissions occurring in the cellulosic chains allows a direct correlation between
      the product yields and the extent of the polymer breakdown. The effect of the
      acid strength on the depolymerization of cellulose is discussed in detail.
      Practical aspects of the reaction, concerning the homogeneous nature of the
      catalysis in spite of the use of a solid acid catalyst, are thoroughly addressed.
      The effect of impurities present in the imidazolium-based ionic liquids on the
      reaction performance, the suitability of different ionic liquids as solvents, and
      the recyclability of Amberlyst 15DRY and BMIMCl are also presented.

PMID- 20155775
TI  - A brief history of phytochromes.
AB  - Photosensory proteins enable living things to detect the quantity and quality of
      the light environment and to transduce that physical signal into biochemical
      outputs which entrain their metabolism with the ambient light environment.
      Phytochromes, which photoconvert between red-absorbing P(r) and far-red-absorbing
      P(fr) states, are the most extensively studied of these interesting proteins.
      Critical regulators of a number of key adaptive processes in higher plants,
      including photomorphogenesis and shade avoidance, phytochromes are widespread in
      photosynthetic and nonphotosynthetic bacteria, and even in fungi. Cyanobacterial
      genomes also possess a plethora of more distant relatives of phytochromes known
      as cyanobacteriochromes (CBCRs). Biochemical characterization of representative
      CBCRs has demonstrated that this class of photosensors exhibits a broad range of
      wavelength sensitivities, spanning the entire visible spectrum. Distinct protein
      bilin interactions are responsible for this astonishing array of wavelength
      sensitivities. Despite this spectral diversity, all members of the extended
      family of phytochrome photosensors appear to share a common photochemical
      mechanism for light sensing: photoisomerization of the 15/16 double bond of the
      bilin chromophore.

PMID- 20155778
TI  - Structure-function correlations for Ru/CNT in the catalytic decomposition of
      ammonia.

PMID- 20155779
TI  - Towards solar fuels from water and CO2.
AB  - Solar fuels from water and CO2 are a topic of current large scientific and
      industrial interest. Research advances on bioroutes, concentrated solar thermal
      and low-temperature conversion using semiconductors and a photoelectrocatalytic
      (PEC) approach, are critically discussed and compared in an attempt to define
      challenges and current limits and to identify the priorities on which focus
      research and development (R&D). The need to produce fuels that are easy to
      transport and store, which can be integrated into the existing energy
      infrastructure, is emphasized. The role of solar fuels produced from CO2 in
      comparison with solar H2 is analyzed. Solar fuels are complementary to solar to
      electrical energy conversion, but they still need intensified R&D before possible
      commercialization.

PMID- 20155780
TI  - Nanochemical concepts for a sustainable energy supply.

PMID- 20155781
TI  - Combination of different liquid chromatography/mass spectrometry technologies for
      the identification of transformation products of rhodamine B in groundwater.
AB  - Rhodamine B and its five de-ethylated transformation products could be identified
      in a groundwater sample. Using high-performance thin-layer chromatography (HPTLC)
      six fluorescent zones were detected in the sample. In order to identify the
      compounds in the zones by exact mass mass spectrometry (MS) measurements and
      tandem mass spectrometry (MS/MS), they were extracted from the HPTLC plate for
      subsequent analysis by nano-chip high-performance liquid chromatography
      quadrupole-time-of-flight mass spectrometry (nano-chip HPLC/QTOFMS). In addition,
      chemical derivatisation experiments on HPTLC plates were applied to detect the
      presence of a primary amino group in the transformation products. From the
      combined analytical results it was possible to allocate rhodamine B and its five
      de-ethylated transformation products to the six different HPTLC zones. The
      quantification of rhodamine B in different groundwater samples was carried out by
      a high-performance liquid chromatography/triple quadrupole mass spectrometry
      (HPLC/MS/MS). The maximum detected concentration of rhodamine B was 83 microg L(
      1).

PMID- 20155782
TI  - Prenatal diagnosis of double aortic arch and D-transposition of the great
      arteries: a case report.

PMID- 20155783
TI  - Maternal serum anti-Mullerian hormone level is not superior to chronological age
      in predicting Down syndrome pregnancies.
AB  - OBJECTIVE: To compare the difference in maternal serum anti-Mullerian hormone
      (AMH) level between Down syndrome pregnancies and unaffected pregnancies, and to
      evaluate its performance as a screening marker for Down syndrome pregnancy.
      METHOD: A total of 145 pregnancies affected by foetal Down syndrome and 290
      unaffected controls matched with maternal age and gestational age were selected,
      and their archived first or second trimester serum retrieved for AMH assay.
      RESULTS: There was no significant difference in maternal serum AMH level between
      pregnancies affected and unaffected by foetal Down syndrome. Our first trimester
      serum samples had higher AMH concentration compared to second trimester samples.
      CONCLUSIONS: Maternal serum AMH level, as a marker of ovarian age, is not
      superior to chronological age in predicting Down syndrome pregnancies. Despite
      the cross-sectional nature of our study, the variation of maternal serum AMH
      concentration with gestational age warrants further investigation.

PMID- 20155784
TI  - Hepatitis B virus activates deoxynucleotide synthesis in nondividing hepatocytes
      by targeting the R2 gene.
AB  - Hepatitis B virus (HBV) causes liver diseases from acute hepatitis to cirrhosis
      and liver cancer. Currently, more than 350 million people are chronic HBV
      carriers, with devastating prognosis. HBV is a small enveloped noncytopathic
      virus, containing a circular partially double-stranded DNA genome, and exhibits
      strong tropism for human liver cells. Infected individuals (acute and chronic)
      secrete about 10(7) to 10(11) virions per day to the bloodstream, with each
      infected cell releasing 50-300 viruses per day. HBV infects nondividing
      hepatocytes and replicates by reverse-transcribing the pregenomic RNA to DNA in
      the host cells. The level of deoxyribonucleotide triphosphates (dNTPs) in
      nondividing cells is too low to support viral replication and enable the high
      yield of secreted virions. Here, we report production of dNTPs by viral-dependent
      transcription activation of R2, the key component of ribonucleotide reductase
      (RNR), and show that this process is critical for the HBV life-cycle. This was
      found in an established HBV-positive cell line and was reproduced by HBV DNA
      transduced cells, in both culture and mice. Furthermore, the viral hepatitis B X
      protein is essential in activating R2 expression by blocking access of Regulatory
      factor x1, a repressor of the R2 gene. CONCLUSION: Our findings demonstrate that
      the hepatitis B X protein is critical in infecting nonproliferating hepatocytes,
      which contain a low dNTP level. In addition, we provide molecular evidence for a
      new mechanism of HBV-host cell interaction where RNR-R2, a critical cell-cycle
      gene, is selectively activated in nonproliferating cells. This mechanism may set
      the stage for formulating a new category of anti-HBV drugs.

PMID- 20155786
TI  - Near-infrared Raman spectroscopy for early diagnosis and typing of adenocarcinoma
      in the stomach.
AB  - BACKGROUND: The aim of this study was to evaluate the feasibility of using near
      infrared (NIR) Raman spectroscopy for early diagnosis and typing of intestinal
      and diffuse adenocarcinoma of the stomach. METHODS: A dispersive-type NIR Raman
      system was used for tissue measurements. One hundred gastric tissue samples from
      62 patients who underwent endoscopy or gastrectomy were used (70 normal tissue
      specimens and 30 adenocarcinomas). Principal components analysis (PCA) and
      multinomial logistic regression (MNLR) were used to develop diagnostic algorithms
      for tissue classification. RESULTS: High-quality Raman spectra ranging from 800
      to 1800 cm(-1) were acquired from gastric tissue within 5 s. There were
      significant differences in Raman spectra between normal stomach and the two
      gastric adenocarcinoma subtypes, particularly in the spectral ranges 850-1150,
      1200-1500 and 1600-1750 cm(-1), which contain signals related to proteins,
      nucleic acids and lipids. PCA-MNLR achieved predictive accuracies of 88, 92 and
      94 per cent for normal stomach, and intestinal- and diffuse-type gastric
      adenocarcinomas respectively. CONCLUSION: NIR Raman spectroscopy can detect
      gastric malignancy and identify the subtype of gastric adenocarcinoma.

PMID- 20155787
TI  - Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens
      for rectal cancer.
AB  - BACKGROUND: To address issues regarding the fractionation of radiotherapy (RT)
      and timing of surgery for rectal cancer, a multicentre trial has randomized
      patients to preoperative short-course RT with two different intervals to surgery,
      or long-course RT with delayed surgery. The present interim analysis assessed
      feasibility, compliance and complications after RT and surgery. METHODS: Some 303
      patients were randomized to either short-course RT (5 x 5 Gy) and surgery within
      1 week (group 1), short-course RT and surgery after 4-8 weeks (group 2) or long
      course RT (25 x 2 Gy) and surgery after 4-8 weeks (group 3). RESULTS: Demographic
      data were similar between groups and there were few protocol violations (5.0-6
      per cent). Eight patients (2.6 per cent) developed radiation-induced acute
      toxicity. There were no significant differences in postoperative complications
      between groups (46.6, 40.0 and 32 per cent in groups 1, 2 and 3 respectively; P =
      0.164). Patients receiving short-course RT with surgery 11-17 days after the
      start of RT had the highest complication rate (24 of 37). CONCLUSION: Compliance
      was acceptable and severe acute toxicity was low, irrespective of fractionation.
      Short-course RT with immediate surgery had a tendency towards more postoperative
      complications, but only if surgery was delayed beyond 10 days after the start of
      RT. REGISTRATION NUMBER: NCT00904813 (http://www.clinicaltrials.gov).

PMID- 20155788
TI  - Randomized controlled trial of pelvic calcium alginate following rectal cancer
      surgery.
AB  - BACKGROUND: The aim of this randomized controlled trial was to assess the
      possible benefit of using a new haemostatic agent (Hemoionic) in the pelvic
      cavity in sphincter-saving surgery for rectal cancer. METHODS: Eighty-five
      patients undergoing elective sphincter-saving rectal resection for cancer were
      randomized into Hemoionic (41 patients) and control (44) groups. In both groups,
      a pelvic suction drain was left in place for as long as the daily output exceeded
      20 ml. The primary endpoint was volume of fluid collected by the suction drain;
      secondary endpoints were duration of drainage, and postoperative mortality and
      morbidity rates. RESULTS: The mean total drainage volume was significantly lower
      in the Hemoionic group (453 ml versus 758 ml in control group; P = 0.031). There
      was no significant difference between groups in duration of drainage and
      morbidity. The mortality rate was four of 41 in the Hemoioni group and one of 44
      in the control group (P = 0.192). CONCLUSION: Hemoionic may reduce the drainage
      volume after sphincter-saving surgery for rectal cancer, but offers no clinical
      advantage. REGISTRATION NUMBER: ISRCTN79721331 (http://www.isrctn.org).

PMID- 20155789
TI  - Laparoscopic resection with transcolonic specimen extraction for ileocaecal
      Crohn's disease.
AB  - BACKGROUND: Ileocolic resection for Crohn's disease can be performed entirely
      laparoscopically. However, an incision is needed for specimen extraction. This
      prospective observational study assessed the feasibility of endoscopic
      transcolonic specimen removal. METHODS: Endoscopic specimen removal was attempted
      in a consecutive series of ten patients scheduled for laparoscopic ileocolic
      resection. Primary outcomes were feasibility, operating time, reoperation rate,
      pain scores, morphine requirement and hospital stay. To assess applicability,
      outcomes were compared with previous data from patients who had laparoscopically
      assisted operations. RESULTS: Transcolonic removal was successful in eight of ten
      patients; it was considered not feasible in two patients because the inflammatory
      mass was too large (7-8 cm). Median operating time was 208 min and median
      postoperative hospital stay was 5 days. After surgery two patients developed an
      intra-abdominal abscess, drained laparoscopically or percutaneously, and one
      patient had another site-specific infection. The operation took longer than
      conventional laparoscopy, with no benefits perceived by patients in terms of
      cosmesis or body image. CONCLUSION: Transcolonic removal of the specimen in
      ileocolic Crohn's disease is feasible in the absence of a large inflammatory mass
      but infection may be a problem. It is unclear whether the technique offers
      benefit compared with conventional laparoscopic surgery.

PMID- 20155790
TI  - Meta-analysis of small randomized controlled trials in surgery may be unreliable.
AB  - BACKGROUND: Meta-analysis of randomized controlled trials (RCTs) should provide
      reliable evidence about the effects of interventions. This may be less reliable
      when only small trials are available. METHODS: The sample size was determined for
      all surgical RCTs included in Cochrane Collaboration systematic reviews. The
      difficulty in interpreting meta-analysis of small trials is illustrated using two
      specific reviews. RESULTS: The typical sample size for surgical RCTs was small
      with a median of only 87 participants. Only 39.8 per cent had adequate
      prerandomization treatment allocation concealment. In both systematic reviews
      that were assessed in detail, statistically significant early results from meta
      analysis of several small RCTs did not reliably predict the results of subsequent
      RCTs. CONCLUSION: Surgical RCTs tend to be small and underpowered. Meta-analysis
      of such trials does not necessarily produce reliable results.

PMID- 20155791
TI  - Helicobacter bilis colonization of the biliary system in patients with
      pancreaticobiliary maljunction.
AB  - BACKGROUND: Helicobacter bilis is considered to be a causative factor in the
      pathogenesis of biliary cancer. This study investigated the prevalence of H.
      bilis colonization of the biliary system of patients with pancreaticobiliary
      maljunction (PBM). METHODS: Bile juice and biliary tissue samples were collected
      from 17 patients with PBM and 27 controls who had benign biliary disease without
      PBM. DNA extracted from each biliary sample was subjected to polymerase chain
      reaction (PCR) analysis for H. bilis and Helicobacter pylori. RESULTS: PCR assays
      revealed that 12 of the 17 patients with PBM were positive for H. bilis DNA,
      compared with eight of 27 patients without PBM (P = 0.009). Among patients with
      PBM, H. bilis DNA was identified in six of eight children, including a 2-month
      old infant, and in six of nine adults. The high prevalence of H. bilis DNA in the
      biliary system of patients with PBM was independent of age, sex, common bile duct
      dilatation, configuration of the pancreatic and bile ducts, and amylase activity
      in bile. CONCLUSION: H. bilis colonization of the biliary system is extremely
      common in patients with PBM. This may point to a role in the pathogenesis of
      biliary cancer.

PMID- 20155792
TI  - Health-related quality of life after minimally invasive oesophagectomy.
AB  - BACKGROUND: Open oesophagectomy has a detrimental impact on health-related
      quality of life (HRQL), with recovery taking up to a year. Minimally invasive
      oesophagectomy (MIO) may enable a more rapid recovery of HRQL. METHODS: Clinical
      outcomes from consecutive patients undergoing MIO for cancer were recorded
      between April 2005 and April 2007. Patients completed validated questionnaires,
      European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OES18,
      before surgery and at 6 weeks, 3, 6 and 12 months after surgery. RESULTS: MIO for
      cancer or high-grade dysplasia was planned in 62 patients, but abandoned in four
      owing to occult metastatic disease. Resection was completed in the remaining 58,
      two having partial conversion to open surgery. There was one in-hospital death
      and 29 patients developed complications. At 1 year, 52 of 58 patients were alive.
      Questionnaire response rates were high at each time point (overall compliance 84
      per cent). Six weeks after MIO, patients reported deterioration in functional
      aspects of HRQL and more symptoms than at baseline. However, most improved by 3
      months and had returned to baseline levels by 6 months. These levels were
      maintained 1 year after surgery, with 85 per cent of patients recovering in more
      than 50 per cent of the HRQL domains. CONCLUSION: MIO leads to a rapid
      restoration of HRQL.

PMID- 20155793
TI  - Propensity scored analysis of outcomes after ruptured abdominal aortic aneurysm.
AB  - BACKGROUND: This study examined the population outcome of ruptured abdominal
      aortic aneurysm (rAAA) in England, the role of endovascular repair (EVAR), and
      the relationship between outcome and hospital workload. METHODS: Data were
      retrieved from Hospital Episode Statistics between 1 April 2003 and 31 March
      2008. Propensity scoring was used to compare the outcomes of stratified patients
      undergoing EVAR and open repair. The relationship between workload and outcome
      was determined. RESULTS: Some 3725 urgent and 4414 rAAA repairs were included.
      Mortality rates were 21.3 per cent for urgent repair and 46.3 per cent for rAAA
      repair. EVAR was employed for 16.3 and 7.6 per cent of urgent and rAAA repairs
      respectively. EVAR was associated with significantly reduced mortality for urgent
      repair (odds ratio (OR) 0.531, 95 per cent confidence interval 0.415 to 0.680; P
      < 0.001) and rAAA repair (OR 0.527, 0.416 to 0.668; P < 0.001). A propensity
      scored analysis confirmed the benefit of EVAR for rAAA repair (P < 0.001). Repair
      of rAAA at hospitals with a higher elective aneurysm workload was associated with
      lower mortality rates irrespective of the mode of treatment (P < 0.001). Higher
      volume hospitals were more likely to operate on rAAA (P = 0.033). CONCLUSION:
      EVAR offered a survival advantage over open repair for non-elective aneurysm
      procedures. Services for the treatment of rAAA should incorporate access to EVAR
      and would benefit from being based in units with a high elective caseload.

PMID- 20155794
TI  - Nest groups of wild bonobos at Wamba: selection of vegetation and tree species
      and relationships between nest group size and party size.
AB  - We examined the location of nest groups, spatial distribution of nests within a
      nest group, and attributes of individual nests of wild bonobos at Wamba,
      Democratic Republic of Congo. We also examined the seasonal factors influencing
      nesting behavior and compared the nest group size with the 1 hr party size during
      daytime. We defined a nest group to be a cluster of nests that were built in the
      same evening and found within 30 m from the other nearest nest. Examination of
      the largest gap within a nest group suggested that 30 m was an acceptable cutoff
      value. Monthly rainfall or fruit abundance did not significantly influence the
      monthly mean nest group size. Nests were built in the swamp forest for as many as
      13% observation days, suggesting the need for reevaluation of the use of swamp
      forest by bonobos. The use of swamp forest was influenced not by seasonal
      rainfall or fruit abundance, but by the fruiting of specific species. Preferred
      tree species for building nests accounted for 19.8% of standing trees, which
      suggested that the selection of sleeping sites was not largely restricted by the
      distribution of specific species. The mean 1 hr party size was almost identical
      through the day and was similar to the mean nest group size. Parties of bonobos
      sometimes split into smaller nest groups, especially when feeding on non
      preferred fruits during fruit scarcity. By contrast, when feeding on preferred
      fruits while ranging in large parties, they often aggregated to form even larger
      nest groups. When sleeping in small- or middle-sized nest groups, they tended to
      aggregate the next morning. These tendencies may reflect the gregarious nature of
      bonobos who prefer to range or sleep together as far as circumstances allow.

PMID- 20155795
TI  - Plasma cholesterol and Parkinson's disease: is the puzzle only apparent?

PMID- 20155797
TI  - Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kappaB
      promotes apoptotic neuronal cell death in the hippocampus following experimental
      status epilepticus.
AB  - Whereas status epilepticus, or the condition of continuous epileptic seizures,
      produces a characteristic pattern of preferential neuronal cell loss in the
      hippocampus, the underlying mechanism is still unsettled. Based on an
      experimental model of temporal lobe status epilepticus, we demonstrated
      previously that prolonged seizures prompted an overproduction of nitric oxide
      (NO) by upregulation of NO synthase II (NOS II) in the hippocampal CA3 subfield,
      followed by the activation of mitochondrial apoptotic signaling cascade. Using
      the same animal model, the present study evaluated the hypothesis that
      transcriptional upregulation of NOS II gene by nuclear factor-kappaB (NF-kappaB)
      promotes apoptotic neuronal cell death in the hippocampus following status
      epilepticus. In Sprague-Dawley rats, significantly augmented nucleus-bound
      translocation of NF-kappaB p50 and p65 subunits and DNA binding activity of NF
      kappaB were observed in hippocampal CA3 neurons as early as 30 min after
      elicitation of sustained seizure activity by microinjection of kainic acid into
      the CA3 subfield, followed by a progressive elevation that peaked at 90 min. In
      addition, application bilaterally into the hippocampal CA3 subfield of a
      selective NF-kappaB inhibitor, pyrrolidine dithiocarbamate or double-stranded
      kappaB decoy DNA significantly antagonized the activated NOS II-peroxynitrite
      signaling cascade (3 hr) and the associated manifestations of apoptotic cell
      death (7 days) in the hippocampus. We conclude that activation of NF-kappaB in
      hippocampal CA3 neurons upregulates NOS II gene expression following experimental
      temporal lobe status epilepticus, leading to apoptotic neuronal cell death in the
      hippocampus.

PMID- 20155798
TI  - Evaluation of velopharyngeal function after relocation pharyngoplasty for
      obstructive sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: To assess if relocation pharyngoplasty (RP) causes
      velopharyngeal dysfunction in patients with obstructive sleep apnea (OSA) by
      evaluating perioperative nasalance, nasality, voice, and articulation. STUDY
      DESIGN: Prospective, comparative study. METHODS: Twenty-four OSA patients
      selected for RP (two women and 22 men; mean age, 35 years) were enrolled for the
      study of velopharyngeal function in speech. The RP procedure involved removal of
      supratonsillar adipose tissue, preservation of all palatal muscular structure,
      splinting the lateral pharyngeal wall, and anterior advancing of the soft palate.
      Measurements of nasalance (vowel /a/, /i/, consonant /m/, oronasal, oral, and
      nasal texts), nasality (mirror-fogging test, degree of nasality, Gutzmann test
      and Bzoch hypernasality test), voice (acoustic analysis), and articulation (velar
      sound) were taken before RP and 3 months after the procedure and compared.
      RESULTS: Comparative analysis of clinical measures showed that no significant
      differences were found following RP in nasalance (except for the vowel /a/),
      nasality, articulation, and voice. The only difference with regard to vowel /a/
      showed, instead of an increase, a significant decrease of nasalance from 17.3 +
      or - 10.8 to 11.3 + or - 6.7 (P = .004), which may be attributed to the advancing
      and lifting of the soft palate in RP, leading to relaxation of the levator veli
      palatine and uvular muscles, which facilitates their contraction in
      velopharyngeal closure during particular vowel phonation. CONCLUSIONS: RP for OSA
      does not cause velopharyngeal insufficiency in terms of voice, nasality, and
      articulation in spite of anterior advancement of the soft palate, but does induce
      a nondetrimental change in nasalance.

PMID- 20155799
TI  - Use of Trellis thrombectomy system in acute aortofemoral graft occlusion.
AB  - Acute aortofemoral graft occlusion is often effectively treated with endovascular
      therapy but a substantial proportion of patients experience failure or
      complications of this therapy, and most of them require definitive surgery for
      the underlying inflow, outflow, or graft disease. We describe a case of an
      aortofemoral graft occlusion that was successfully treated with the Trellis
      thrombectomy-thrombolysis system (Covidien, Dublin, Ireland). Subsequent stenting
      of the graft obviated the need for a definitive graft revision surgery. The
      Trellis system combines mechanical and local pharmacologic lysis of the thrombus,
      with more rapid and more effective thrombus dissolution and theoretically less
      risk of systemic dispersion of the thrombolytic agent and less bleeding.

PMID- 20155800
TI  - Hydroxychloroquine for subglottic stenosis: a novel therapy in the battle for
      air.
AB  - Upper airway obstruction due to subglottic edema and granulation tissue
      proliferation may cause severe morbidity and may be life threatening.
      Hydroxychloroquine interferes with antigen processing by means of raising
      lysosomal pH and immune response modulation. Herein, we present the outcome of a
      steroid-sparing treatment using hydroxychloroquine in an 80-year-old man with
      acquired subglottic stenosis and steroid dependency. Twice daily oral
      hydroxychloroquine at 2 mg/kg/day allowed cessation of systemic steroids without
      recurrence of the stenosis. Successful weaning of the hydroxychloroquine took
      place over a 5-month period.

PMID- 20155802
TI  - ViewIT improves intravascular ultrasound-guided wiring in coronary intervention
      of chronic total occlusion.
AB  - Terumo intravascular ultrasound (IVUS) ViewIT facilitates IVUS-guided wiring in
      percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) due to
      its low profile and surface coating. In PCI for CTO, the first guidewire is
      sometimes inserted into the subintimal space, and observation by IVUS through the
      first guidewire in the subintima can allow the second guidewire to be led
      visually into the true lumen. We describe a case of CTO in which ViewIT was
      inserted into the subintimal space of the CTO lesion and scanning from the
      coronary ostium to the CTO subintimal space allowed the second guidewire to be
      led into the true lumen.

PMID- 20155801
TI  - Inflammation-induced preterm birth alters neuronal morphology in the mouse fetal
      brain.
AB  - Adverse neurological outcome is a major cause of long-term morbidity in ex
      preterm children. To investigate the effect of parturition and inflammation on
      the fetal brain, we utilized two in vivo mouse models of preterm birth. To mimic
      the most common human scenario of preterm birth, we used a mouse model of
      intrauterine inflammation by intrauterine infusion of lipopolysaccharide (LPS).
      To investigate the effect of parturition on the immature fetal brain, in the
      absence of inflammation, we used a non-infectious model of preterm birth by
      administering RU486. Pro-inflammatory cytokines (IL-10, IL-1beta, IL-6 and TNF
      alpha) in amniotic fluid and inflammatory biomarkers in maternal serum and
      amniotic fluid were compared between the two models using ELISA. Pro-inflammatory
      cytokine expression was evaluated in the whole fetal brains from the two models.
      Primary neuronal cultures from the fetal cortex were established from the
      different models and controls in order to compare the neuronal morphology. Only
      the intrauterine inflammation model resulted in an elevation of inflammatory
      biomarkers in the maternal serum and amniotic fluid. Exposure to inflammation
      induced preterm birth, but not non-infectious preterm birth, also resulted in an
      increase in cytokine mRNA in whole fetal brain and in disrupted fetal neuronal
      morphology. In particular, Microtubule-associated protein 2 (MAP2) staining was
      decreased and the number of dendrites was reduced (P < 0.001, ANOVA between
      groups). These results suggest that inflammation-induced preterm birth and not
      the process of preterm birth may result in neuroinflammation and alter fetal
      neuronal morphology.

PMID- 20155803
TI  - Tieg1/Klf10 is upregulated by NGF and attenuates cell cycle progression in the
      pheochromocytoma cell line PC12.
AB  - The transcription factor Tieg1/Klf10 belongs to a family of Sp1/Klf proteins that
      have been shown to play important roles during development and maintenance of
      various tissues and cell types. Upregulation of Tieg1/Klf10 has been reported for
      TGF-beta, BMP2, BMP4, ActivinA and GDNF as members of the TGF-beta superfamily.
      Moreover, estrogen, the cytostatic drugs homoharringtonine and velcade as well as
      nitric oxide are also able to trigger Tieg1/Klf10 transcription. Recent studies
      suggest a role for members of the neurotrophin family in regulating Tieg1/Klf10
      transcriptional upregulation. Using semi-quantitative RT-PCR and immunoblotting,
      we present data describing that nerve growth factor (NGF) regulates the
      expression of Tieg1/Klf10 in the pheochromocytoma cell line PC12 in a TrkA
      dependent manner. Moreover, we provide evidence for the existence of NGF
      responsive elements in the 5'-regulatory region of Tieg1/Klf10 that contain
      binding sites for the transcription factors Sp1 and CREB. After treatment with
      NGF PC12 cells exit the cell cycle and start to differentiate towards a neuron
      like phenotype indicated by neurite outgrowth. Using flow cytometry and
      differentiation assays we demonstrate that Tieg1/Klf10 reduces cell cycle
      progression in PC12 cells but fails to promote their terminal differentiation.
      Together, our results identify Tieg1/Klf10 as a new NGF target gene and
      substantiate its anti-proliferative function in the NGF signaling pathway in PC12
      cells.

PMID- 20155804
TI  - Percutaneous transcatheter arterial embolization of inferior pancreatico-duodenal
      artery aneurysms associated with celiac artery stenosis or occlusion.
AB  - OBJECTIVES: To report our experience with percutaneous TAE of true IPDA
      aneurysms. BACKGROUND: Most IPDA aneurysms are ruptured at presentation causing a
      high mortality risk. Minimally invasive treatment approaches may improve overall
      outcomes in such patients. METHODS: Between 1996 and 2007, seven patients (5
      Males; mean age 55 y) with symptomatic IPDA aneurysms and severe degree (>75%)
      celiac artery stenosis were treated with percutaneous TAE. The medical and
      imaging records were reviewed for demographics, clinical presentation, treatment,
      complications and follow-up. Patients presented with epigastric pain (7/7),
      hemodynamic shock (2/7) and rectal bleeding (2/7). Selective catheter angiography
      was performed in all patients with the intent to embolize the aneurysms. RESULTS:
      A total of nine aneurysms were seen in seven patients. Two patients had two
      aneurysms each. The aneurysms ranged in size from 0.5 to 4.0 cm (mean 1.9 cm).
      Trans-catheter coil embolization was successful in 8/9 (89%) aneurysms in 6
      patients. Following unsuccessful TAE of one aneurysm in one of the patient, the
      aneurysm was treated successfully with direct CT-guided percutaneous
      transabdominal injection of N-butyl-2-cyanoacrylate. There were no complications
      on follow up. Angioplasty and stenting of the celiac artery were performed in one
      patient for complete occlusion. None of the patients developed clinical or
      imaging evidence of visceral ischemia following embolization. None had recurrent
      symptoms during clinical follow-up (median 3 years, range 0.5-13.5 years). Follow
      up CT (Median 6.6 months, range 4 days-11.5 years) in all patients showed no
      recurrence of the aneurysm. CONCLUSION: IPDA aneurysms associated with celiac
      axis stenosis can be successfully treated with percutaneous embolization with
      minimal recurrence.

PMID- 20155805
TI  - Normal thermoregulatory responses to 3-iodothyronamine, trace amines and
      amphetamine-like psychostimulants in trace amine associated receptor 1 knockout
      mice.
AB  - 3-Iodothyronamine (T1AM) is a metabolite of thyroid hormone. It is an agonist at
      trace amine-associated receptor 1 (TAAR1), a recently identified receptor
      involved in monoaminergic regulation and a potential novel therapeutic target.
      Here, T1AM was studied using rhesus monkey TAAR1 and/or human dopamine
      transporter (DAT) co-transfected cells, and wild-type (WT) and TAAR1 knock-out
      (KO) mice. The IC(50) of T1AM competition for binding of the DAT-specific radio
      ligand [(3)H]CFT was highly similar in DAT cells, WT striatal synaptosomes and KO
      striatal synaptosomes (0.72-0.81 microM). T1AM inhibition of 10 nM [(3)H]dopamine
      uptake (IC(50): WT, 1.4 + or - 0.5 microM; KO, 1.2 + or - 0.4 microM) or 50 nM
      [(3)H]serotonin uptake (IC(50): WT, 4.5 + or - 0.6 microM; KO, 4.7 + or - 1.1
      microM) in WT and KO synaptosomes was also highly similar. Unlike other TAAR1
      agonists that are DAT substrates, TAAR1 signaling in response to T1AM was not
      enhanced in the presence of DAT as determined by CRE-luciferase assay. In vivo,
      T1AM induced robust hypothermia in WT and KO mice equivalently and dose
      dependently (maximum change degrees Celsius: 50 mg/kg at 60 min: WT -6.0 + or -
      0.4, KO -5.6 + or - 1.0; and 25 mg/kg at 30 min: WT -2.7 + or - 0.4, KO -3.0 + or
      - 0.2). Other TAAR1 agonists including beta-phenylethylamine (beta-PEA), MDMA
      (3,4-methylenedioxymethamphetamine) and methamphetamine also induced significant,
      time-dependent thermoregulatory responses that were alike in WT and KO mice.
      Therefore, TAAR1 co-expression does not alter T1AM binding to DAT in vitro nor
      T1AM inhibition of [(3)H]monoamine uptake ex vivo, and TAAR1 agonist-induced
      thermoregulatory responses are TAAR1-independent. Accordingly, TAAR1-directed
      compounds will likely not affect thermoregulation nor are they likely to be
      cryogens.

PMID- 20155806
TI  - Transradial carotid stenting in a patient with bovine arch anatomy.
AB  - Carotid stenting in difficult arch anatomy can be safely done by transradial
      route depending upon operator's experience. Left carotid artery stenosis with
      bovine arch anatomy can be approached by right arm approach (radial/brachial)
      easily. In cases with bovine arch anatomy, left arm approach by modified looping
      technique is still possible. We report a case of carotid stenting in a patient
      with bovine arch anatomy using percusurge anchoring technique through left radial
      approach.

PMID- 20155807
TI  - Elevation of heme oxygenase-1 by proteasome inhibition affords dopaminergic
      neuroprotection.
AB  - Postmortem studies have shown that heme oxygenase-1 (HO-1) immunoreactivity is
      increased in patients with Parkinson disease. HO-1 expression is highly
      upregulated by a variety of stress. Since the proteasome activity is decreased in
      patients with Parkinson disease, we investigated whether proteasome activity
      regulates HO-1 content. MG-132, a proteasome inhibitor, increased the amount of
      HO-1 protein mainly in astrocytes of primary mesencephalic cultures. Quantitative
      RT-PCR analysis revealed that lactacystin upregulated HO-1 mRNA expression.
      Proteasome inhibition with MG132 also increased the cytomegalovirus promoter
      driven expression of Flag-HO-1 protein and resulted in an accumulation of
      ubiquitinated Flag-HO-1 in Flag-HO-1-overexpressing PC12 cells. In addition, a
      cycloheximide chase assay demonstrated that the degradation of Flag-HO-1 protein
      was slowed by MG-132. Next, the function of HO-1 which was upregulated by
      proteasome inhibitors was examined. Proteasome inhibitors protected dopaminergic
      neurons from 6-hydroxydopamine (6-OHDA)-induced toxicity and this neuroprotection
      was abrogated by co-treatment with zinc protoporphyrin IX, a HO-1 inhibitor.
      Furthermore, 6-OHDA-induced toxicity was blocked by bilirubin and carbon
      monoxide, products of the HO-1-catalyzed degradation of heme. These results
      suggest that mesencephalic HO-1 protein level is regulated by proteasome activity
      and the elevation by proteasome inhibition affords neuroprotection.

PMID- 20155808
TI  - Secreted amyloid precursor protein and holo-APP bind amyloid beta through
      distinct domains eliciting different toxic responses on hippocampal neurons.
AB  - Amyloid beta (Abeta) is a metabolic product of Abeta precursor protein (APP).
      Deposition of Abeta in the brain and neuronal degeneration are characteristic
      hallmarks of Alzheimer's disease (AD). Abeta induces neuronal degeneration, but
      the mechanism of neurotoxicity remains elusive. Increasing evidence implicates
      APP as a receptor-like protein for Abeta fibrils (fAbeta). In this study, we
      present further experimental support for the direct interaction of APP with
      fAbeta and for its involvement in Abeta neurotoxicity. Using recombinant purified
      holo-APP (h-APP), we have shown that it directly binds fAbeta. Employing deletion
      mutant forms of APP, we show that two different sequences are involved in the
      binding of APP to fAbeta. One sequence in the n-terminus of APP is required for
      binding of fAbeta to secreted APP (s-APP) but not to h-APP. In addition, the
      extracellular juxtamembrane Abeta-sequence mediates binding of fAbeta to h-APP
      but not to s-APP. Deletion of the extracellular juxtamembrane Abeta sequence
      abolishes abnormal h-APP accumulation and toxicity induced by fAbeta deposition,
      whereas deletions in the n-terminus of APP do not affect Abeta toxicity. These
      experiments show that interaction of toxic Abeta species with its membrane
      anchored parental protein promotes toxicity in hippocampal neurons, adding
      further support to an Abeta-receptor-like function of APP directly implicated in
      neuronal degeneration in AD.

PMID- 20155809
TI  - Tumor necrosis factor, lymphotoxin and cancer.
AB  - Initially TNF has been discovered as an anti-tumor factor, but it is now
      considered as one of the universal effectors of innate signaling implicating its
      key role in host defense and inflammation. Other physiological functions of TNF
      are primarily linked to organization of lymphoid tissues. TNF can exert
      deleterious effects on the organism when its local or systemic concentrations
      exceed certain levels. This is the main reason for the failure of TNF therapy in
      oncology. Moreover, in certain experimental models TNF to TNFRp55 signaling axis
      was found to play a pro-tumorigenic role. On the other hand, anti-TNF therapy
      proved to be beneficial in rheumatic and other autoimmune diseases. Taking into
      consideration the pivotal function of TNF in the immune system, it is obvious
      that such therapy cannot be entirely free of adverse effects including
      suppression of host defense and, possibly, predisposition to lymphomas.
      Lymphotoxins alpha and beta are the two related cytokines that exist in distinct
      trimeric forms which can signal through TNFR I and TNFR II, as well LTbetaR
      receptors, depending on the composition of the trimer. These signals have
      important functions in the development and homeostasis of the immune system.
      Importantly, there is a recently uncovered link between the LTalpha/LTbeta to
      LTbetaR signaling axis and cancer. Here we review the current status of the field
      with the focus on one particular issue: are TNF and lymphotoxins intrinsically
      anti-cancer or pro-tumorigenic.

PMID- 20155810
TI  - Association of the glucocorticoid receptor with STAT3, C/EBPbeta, and the hormone
      responsive element within the rat haptoglobin gene promoter during the acute
      phase response.
AB  - Upregulation of haptoglobin (Hp) expression in the rat during the acute phase
      (AP) response is the result of synergistic effects of IL-6-, IL-1beta-, and
      corticosterone-activated signaling pathways. IL-6 signaling terminates in cis
      trans interactions of the Hp gene hormone-responsive element (HRE) with
      transcription factors STAT3 and C/EBPbeta. The aim of this study was to examine
      the unresolved molecular mechanism of glucocorticoid action. A 3-fold rise in
      serum corticosterone at 2 and 4 h of the AP response induced by turpentine
      administration preceded a 2.3-fold increase in the rate of Hp gene transcription
      at 12 h that was accompanied by a 4.8-fold increase in glucocorticoid receptor
      (GR), the appearance of an 86-kDa STAT3 isoform and 3.9-, 1.9-, and 1.7-fold
      increased amounts of 91-kDa STAT3, 35- and 42-kDa C/EBPbeta isoforms in the
      nucleus. These events resulted in 4.6- and 2.5-fold increased Hp levels in the
      liver and serum at 24 h. HRE affinity chromatography and immunoblot analysis
      revealed that maximal occupancy of the HRE with GR, STAT3, and C/EBPbeta at 12 h
      correlated with increased transcriptional activity of the Hp gene.
      Coimmunoprecipitation experiments showed that activated GR established de novo
      interaction with STAT3 isoforms while GR-C/EBPbeta interactions observed during
      basal transcription increased during the AP response. Computer analysis of the
      HRE disclosed two potential GR-binding sites: one overlapping STAT3, another
      adjacent to a C/EBPbeta-binding site. This finding and the experimental results
      suggest that activated GR through direct interactions with STAT3 and C/EBPbeta,
      participates in Hp gene upregulation as a transcriptional coactivator.

PMID- 20155811
TI  - Chronic foot-shock stress potentiates the influx of bone marrow-derived microglia
      into hippocampus.
AB  - For several years, a new population of microglia derived from bone marrow has
      been described in multiple settings such as infection, trauma, and
      neurodegenerative disease. The aim of this study was to investigate the migration
      of bone marrow-derived cells to the brain parenchyma after stress exposure.
      Stress exposure was performed in mice that had received bone marrow
      transplantation from GFP mice, allowing identification of blood-derived elements
      within the brain. Electric foot-shock exposure was chosen because of its ability
      to serve as fundamental and physical stress in mice. Bone marrow-derived GFP(+)
      cells migrated to the ventral part of the hippocampus and acquired a ramified
      microglia-like morphology. Microglia marker Iba1 was expressed by 100% of the
      ramified cells, whereas ramified cells were negative for the astrocyte marker
      GFAP. Compared with the case in the control group, ramified cells significantly
      increased after chronic exposure to stress (5 days). One month after 5 days of
      stress exposure, ramified cells significantly decreased in ventral hippocampus
      compared with the group examined immediately after the last stress exposure. We
      report for the first time the migration of bone marrow-derived cells to the
      ventral hippocampus after stress exposure. These cells have the characteristics
      of microglia. Mechanisms responsible for this migration and their roles in the
      brain remain to be determined.

PMID- 20155812
TI  - Suppression of hypoxia-inducible factor-1alpha and its downstream genes reduces
      acute hyperglycemia-enhanced hemorrhagic transformation in a rat model of
      cerebral ischemia.
AB  - We evaluated a role of hypoxia-inducible factor-1alpha (HIF-1alpha) and its
      downstream genes in acute hyperglycemia-induced hemorrhagic transformation in a
      rat model of focal cerebral ischemia. Male Sprague-Dawley rats weighing 280-300 g
      (n = 105) were divided into sham, 90 min middle cerebral artery occlusion (MCAO),
      MCAO plus HIF-1alpha inhibitors, 2-methoxyestradiol (2ME2) or 3-(5'-hydroxymethyl
      2'-furyl)-1-benzylindazole (YC-1), groups. Rats received an injection of 50%
      dextrose (6 ml/kg intraperitoneally) at 15 min before MCAO. HIF-1alpha inhibitors
      were administered at the onset of reperfusion. The animals were examined for
      neurological deficits and sacrificed at 6, 12, 24, and 72 hr following MCAO. The
      cerebral tissues were collected for histology, zymography, and Western blot
      analysis. The expression of HIF-1alpha was increased in ischemic brain tissues
      after MCAO and reduced by HIF-1alpha inhibitors. In addition, 2ME2 reduced the
      expression of vascular endothelial growth factor (VEGF) and the elevation of
      active matrix metalloproteinase-2 and -9 (MMP-2/MMP-9) in the ipsilateral
      hemisphere. Both 2ME2 and YC-1 reduced infarct volume and ameliorated
      neurological deficits. However, only 2ME2 attenuated hemorrhagic transformation
      in the ischemic territory. In conclusion, the inhibition of HIF-1alpha and its
      downstream genes attenuates hemorrhagic conversion of cerebral infarction and
      ameliorates neurological deficits after focal cerebral ischemia.

PMID- 20155813
TI  - Regulation of cholesterol efflux by amyloid beta secretion.
AB  - Amyloid beta (Abeta) is a key molecule in the pathogenesis of Alzheimer's
      disease, but its physiological function remains unclear. Abeta is produced from
      amyloid precursor protein (APP) by beta- and gamma-secretases, which is enhanced
      by high levels of cellular cholesterol, so cholesterol is a risk factor for
      Alzheimer's disease. This linkage led us to hypothesize that Abeta is produced to
      regulate cellular cholesterol levels in response to high-cholesterol stimulation.
      Here we show that Abeta production caused a reduction of cellular cholesterol
      levels in transfected HEK293 cells and neuronal IMR-32 and Neuro2a cells, which
      was accompanied by an increase in efflux of cholesterol from cells. Fractionation
      of the culture media by ultracentrifugation and subsequent immunoelectron
      microscopic observation revealed that Abeta assembled high-density lipoprotein
      like particles with cellular cholesterol during its secretion. This assembly was
      mediated by the ATP-binding cassette transporter A1. APP transgenic and knockout
      mice exhibited lower and higher levels of cellular cholesterol in their brains,
      suggesting that Abeta-mediated regulation of cellular cholesterol is
      physiological. Furthermore, we found that, when injected into mouse cerebral
      ventricle, reconstituted lipoproteins with Abeta were excreted into the
      peripheral tissues more efficiently than those without Abeta. This result
      suggests that Abeta mediates cholesterol transport from the brain to the
      circulation. We propose, based on these findings, a novel, apolipoprotein-like
      function for Abeta that is involved in maintenance of cellular and cerebral
      cholesterol homeostasis.

PMID- 20155814
TI  - Involvement of Src-suppressed C kinase substrate in experimental autoimmune
      encephalomyelitis: a link between release of astrocyte proinflammatory factor and
      oligodendrocyte apoptosis.
AB  - Src-suppressed C kinase substrate (SSeCKS) is involved in inflammation in the
      central nervous system (CNS), and plays a role in control of cell signaling and
      cytoskeletal arrangement. However, the expression and function of SSeCKS and its
      function in multiple sclerosis (MS) and its common animal model, experimental
      autoimmune encephalomyelitis (EAE) remained to be elucidated. In the present
      study, we first reported that SSeCKS was remarkably increased in astrocytes of
      EAE rats in vivo. TNF-alpha and NO were significantly induced in astrocytes
      stimulated with LPS/IFN-gamma in vitro, which was blocked in astrocytes
      transfected with SSeCKS siRNA. These results indicated that SSeCKS played a role
      in the production of TNF-alpha and NO in astrocytes with inflammatory
      stimulation. As excessive release of TNF-alpha and NO were major mediators in
      autoimmune diseases and correlated with oligodendrocyte cell death, we further
      investigated whether SSeCKS participated in oligodendrocyte apoptosis.
      Conditioned media (CM) from astrocytes treated with LPS/IFN-gamma decreased
      oligodendrocyte cell viability, while siRNA targeted to SSeCKS in astrocytes
      inhibited oligodendrocyte cell death. The results from antibody neutralization
      and NO inhibition suggested that the oligodendrocyte apoptosis may be due to the
      production of astrocyte-derived proinflammatory factors (TNF-alpha and NO). These
      findings revealed that there was a pathogenic interaction between SSeCKS
      expression in astrocytes and oligodendrocyte apoptosis. Understanding the
      mechanism of SSeCKS in the pathogenesis of EAE may contribute to the development
      of new therapeutic strategies against EAE and MS.

PMID- 20155815
TI  - An Fgfr3-iCreER(T2) transgenic mouse line for studies of neural stem cells and
      astrocytes.
AB  - The lack of markers for astrocytes, particularly gray matter astrocytes,
      significantly hinders research into their development and physiological
      properties. We previously reported that fibroblast growth factor receptor 3
      (Fgfr3) is expressed by radial precursors in the ventricular zone of the
      embryonic neural tube and subsequently by differentiated astrocytes in gray and
      white matter. Here, we describe an Fgfr3-iCreER(T2) phage artificial chromosome
      transgenic mouse line that allows efficient tamoxifen-induced Cre recombination
      in Fgfr3-expressing cells, including radial glial cells in the embryonic neural
      tube and both fibrous and protoplasmic astrocytes in the mature central nervous
      system. This mouse strain will therefore be useful for studies of normal
      astrocyte biology and their responses to CNS injury or disease. In addition,
      Fgfr3-iCreER(T2) drives Cre recombination in all neurosphere-forming stem cells
      in the adult spinal cord and at least 90% of those in the adult forebrain
      subventricular zone. We made use of this to show that there is continuous
      accumulation of all major interneuron subtypes in the olfactory bulb (OB) from
      postnatal day 50 (P50) until at least P230 ( approximately 8 months of age). It
      therefore seems likely that adult-born interneurons integrate into existing
      circuitry and perform long-term functions in the adult OB.

PMID- 20155816
TI  - Chemokine expression in the white matter spinal cord precursor niche after force
      defined spinal cord contusion injuries in adult rats.
AB  - Inflammatory cascades induced by spinal cord injuries (SCI) are localized in the
      white matter, a recognized neural stem- and progenitor-cell (NSPC) niche of the
      adult spinal cord. Chemokines, as integrators of these processes, might also be
      important determinants of this NSPC niche. CCL3/CCR1, CCL2/CCR2, and SDF
      1alpha/CXCR4 were analyzed in the ventrolateral white matter after force defined
      thoracic SCI: Immunoreactivity (IR) density levels were measured 2 d, 7 d, 14 d,
      and 42 d on cervical (C 5), thoracic (T 5), and lumbar (L 5) levels. On day post
      operation (DPO) 42, chemokine inductions were further evaluated by real-time RT
      PCR and Western blot analyses. Cellular phenotypes were confirmed by double
      labeling with markers for major cell types and NSPCs (nestin, Musashi-1, NG2,
      3CB2, BLBP). Mitotic profiles were investigated in parallel by BrdU labeling.
      After lesion, chemokines were induced in the ventrolateral white matter on IR-,
      mRNA-, and protein-level. IR was generally more pronounced after severe lesions,
      with soaring increases of CCL2/CCR2 and continuous elevations of CCL3/CCR1. SDF
      1alpha and CXCR4 IR induction was focused on thoracic levels. Chemokines/
      receptors were co-expressed with astroglial, oligodendroglial markers, nestin,
      3CB2 and BLBP by cells morphologically resembling radial glia on DPO 7 to DPO 42,
      and NG2 or Musashi-1 on DPO 2 and 7. In the white matter BrdU positive cells were
      significantly elevated after lesion compared with sham controls on all
      investigated time points peaking in the early time course on thoracic level:
      Here, chemokines were co-expressed by subsets of BrdU-labeled cells. These
      findings suggest an important role of chemokines/-receptors in the subpial white
      matter NSPC niche after SCI.

PMID- 20155817
TI  - The role and therapeutic potential of monocytic cells in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a dementing neurodegenerative disorder without a
      cure. The abnormal parenchymal accumulation of beta-amyloid (Abeta) is associated
      with inflammatory reactions involving microglia and astrocytes. Increased levels
      of Abeta and Abeta deposition in the brain are thought to cause neuronal
      dysfunction and underlie dementia. Microglia, the brain resident cells of
      monocytic origin, have a potential ability to phagocytose Abeta but they also
      react to Abeta by increased production of proinflammatory toxic agents. Microglia
      originate from hemangioblastic mesoderm during early embryonic stages and from
      bone marrow (BM)-derived monocytic cells that home the brain throughout the
      neonatal stage of development. Recent studies indicate that BM or blood-derived
      monocytes are recruited to the diseased AD brain, associate with the Abeta
      depositions, and are more efficient phagocytes of Abeta compared with resident
      microglia. The clearance of Abeta deposition by these cells has been recently
      under intensive investigation and can occur through several different mechanisms.
      Importantly, peripheral monocytic cells of patients with AD appear to be
      deficient in clearing Abeta. This review will summarize the findings on the role
      of blood-derived cells in AD and discuss their therapeutic potential for treating
      patients suffering from this devastating disease.

PMID- 20155819
TI  - Hemangioblastic derivatives from human induced pluripotent stem cells exhibit
      limited expansion and early senescence.
AB  - Human induced pluripotent stem cells (hiPSC) have been shown to differentiate
      into a variety of replacement cell types. Detailed evaluation and comparison with
      their human embryonic stem cell (hESC) counterparts is critical for assessment of
      their therapeutic potential. Using established methods, we demonstrate here that
      hiPSCs are capable of generating hemangioblasts/blast cells (BCs), endothelial
      cells, and hematopoietic cells with phenotypic and morphologic characteristics
      similar to those derived from hESCs, but with a dramatic decreased efficiency.
      Furthermore, in distinct contrast with the hESC derivatives, functional
      differences were observed in BCs derived from hiPSCs, including significantly
      increased apoptosis, severely limited growth and expansion capability, and a
      substantially decreased hematopoietic colony-forming capability. After further
      differentiation into erythroid cells, >1,000-fold difference in expansion
      capability was observed in hiPSC-BCs versus hESC-BCs. Although endothelial cells
      derived from hiPSCs were capable of taking up acetylated low-density lipoprotein
      and forming capillary-vascular-like structures on Matrigel, these cells also
      demonstrated early cellular senescence (most of the endothelial cells senesced
      after one passage). Similarly, retinal pigmented epithelium cells derived from
      hiPSCs began senescing in the first passage. Before clinical application, it will
      be necessary to determine the cause and extent of such abnormalities and whether
      they also occur in hiPSCs generated using different reprogramming methods.

PMID- 20155818
TI  - Genetic ablation of steroid receptor coactivator-3 promotes PPAR-beta-mediated
      alternative activation of microglia in experimental autoimmune encephalomyelitis.
AB  - Steroid receptor coactivator-3 (SRC-3) has been demonstrated to regulate lipid
      metabolism by inhibiting adipocyte differentiation. In this study, the potential
      role of SRC-3 in experimental autoimmune encephalomyelitis (EAE), which
      characterized by inflammatory demyelination in central nervous system (CNS), was
      examined by analyzing disease progression in SRC-3-deficient (SRC-3(-/-)) mice.
      We found that SRC-3 deficiency significantly attenuated the disease severity of
      EAE along with decreased inflammatory infiltration and demyelination. However,
      these effects are not caused by inhibition of peripheral T cell response, but by
      upregulated expression of peroxisome proliferator-activated receptor (PPAR)-beta
      in CNS, which induced an alternative activation state of microglia in SRC-3(-/-)
      mice. These alternatively activated microglia inhibited CNS inflammation through
      inhibition of proinflammatory cytokines and chemokines, such as TNF-alpha, IFN
      gamma, CCL2, CCL3, CCL5, and CXCL10, as well as upregulation of anti-inflammatory
      cytokine IL-10 and opsonins, such as C1qa and C1qb. Moreover, microglia
      alternative activation promoted myelin regeneration through increased
      accumulation of oligodendrocyte precursors in white matter and elevated
      expression of myelin genes in the spinal cords of SRC-3(-/-) mice. Our results
      build up a link between lipid metabolic regulation and immune functions, and the
      modulation of the expression of SRC-3 or PPAR-beta may hopefully has therapeutic
      modality in MS and possibly other neurodegenerative diseases.

PMID- 20155820
TI  - Triptolide promotes spinal cord repair by inhibiting astrogliosis and
      inflammation.
AB  - Spinal cord injury (SCI) is a cause of major neurological disability, and no
      satisfactory treatment is currently available. Traumatic SCI directly damages the
      cell bodies and/or processes of neurons and triggers a series of endogenous
      processes, including neuroinflammatory response and reactive astrogliosis. In
      this study, we found that triptolide, one of the major active components of the
      traditional Chinese herb Tripterygium wilfordii Hook F, inhibited astrogliosis
      and inflammation and promoted spinal cord repair. Triptolide was shown to prevent
      astrocytes from reactive activation by blocking the JAK2/STAT3 pathway in vitro
      and in vivo. Furthermore, astrocytic gliosis and glial scar were greatly reduced
      in injured spinal cord treated with triptolide. Triptolide treatment was also
      shown to decrease the ED-1 or CD11b-positive inflammatory cells at the lesion
      site. Using neurofilament staining and anterograde tracing, a significantly
      greater number of regenerative axons were observed in the triptolide-treated
      rats. Importantly, behavioral tests revealed that injured rats receiving
      triptolide had improved functional recovery as assessed by the Basso, Beattie,
      and Bresnahan open-field scoring, grid-walk, and foot-print analysis. These
      results suggested that triptolide promoted axon regeneration and locomotor
      recovery by attenuating glial scaring and inflammation, and shed light on the
      potential therapeutic benefit for SCI.

PMID- 20155821
TI  - Heterogeneity in progenitor cell subtypes in the ventricular zone of the
      zebrafish adult telencephalon.
AB  - The zebrafish has become a new model for adult neurogenesis, owing to its
      abundant neurogenic areas in most brain subdivisions. Radial glia-like cells,
      actively proliferating cells, and label-retaining progenitors have been described
      in these areas. In the telencephalon, this complexity is enhanced by an
      organization of the ventricular zone (VZ) in fast and slow-dividing domains,
      suggesting the existence of heterogeneous progenitor types. In this work, we
      studied the expression of various transgenic or immunocytochemical markers for
      glial cells (gfap:gfp, cyp19a1b:gfp, BLBP, and S100beta), progenitors (nestin:gfp
      and Sox2), and neuroblasts (PSA-NCAM) in cycling progenitors of the adult
      zebrafish telencephalon (identified by expression of proliferating cell nuclear
      antigen (PCNA), MCM5, or bromodeoxyuridine incorporation). We demonstrate the
      existence of distinct populations of dividing cells at the adult telencephalic
      VZ. Progenitors of the overall slow-cycling domains express high levels of Sox2
      and nestin:gfp as well as all glial markers tested. In contrast, domains with an
      overall fast division rate are characterized by low or missing expression of
      glial markers. PCNA-positive cells in fast domains further display a morphology
      distinct from radial glia and co-express PSA-NCAM, suggesting that they are early
      neuronal precursors. In addition, the VZ contains cycling progenitors that
      express neither glial markers nor nestin:gfp, but are positive for Sox2 and PSA
      NCAM, identifying them as committed neuroblasts. On the basis of the marker gene
      expression and distinct cell morphologies, we propose a classification for the
      dividing cell states at the zebrafish adult telencephalic VZ.

PMID- 20155822
TI  - Schwann cell migration is integrin-dependent and inhibited by astrocyte-produced
      aggrecan.
AB  - Schwann cells transplantation has considerable promise in spinal cord trauma to
      bridge the site of injury and for remyelination in demyelinating conditions. They
      support axonal regeneration and sprouting by secreting growth factors and
      providing a permissive surface and matrix molecules while shielding axons from
      the inhibitory environment of the central nervous system. However, following
      transplantation Schwann cells show limited migratory ability and they are unable
      to intermingle with the host astrocytes. This in turn leads to formation of a
      sharp boundary and an abrupt transition between the Schwann cell graft and the
      host tissue astrocytes, therefore preventing regenerating axons from exiting the
      graft. The objective of this study was to identify inhibitory elements on
      astrocytes involved in restricting Schwann cell migration. Using in vitro assays
      of cell migration, we show that aggrecan produced by astrocytes is involved in
      the inhibition of Schwann cell motility on astrocytic monolayers. Knockdown of
      this proteoglycan in astrocytes using RNAi or digestion of glycosaminglycan
      chains on aggrecan improves Schwann cell migration. We further show aggrecan
      mediates its effect by disruption of integrin function in Schwann cells, and that
      the inhibitory effects of aggrecan can overcome by activation of Schwann cell
      integrins.

PMID- 20155823
TI  - Vibrational and chiroptical spectroscopic characterization of gamma-turn model
      cyclic tetrapeptides containing two beta-Ala residues.
AB  - The optical spectroscopic characterization of gamma-turns in solution is
      uncertain and their distinction from beta-turns is often difficult. This work
      reports systematic ECD and vibrational circular dichroism (VCD) spectroscopic
      studies on gamma-turn model cyclic tetrapeptides cyclo(Ala-beta-Ala-Pro-beta-Ala)
      (1), cyclo(Pro-beta-Ala-Pro-beta-Ala) (2) and cyclo(Ala-beta-Ala-Ala-beta-Ala)
      (3). Conformational analysis performed at the 6-31G(d)/B3LYP level of theory
      using an adequate PCM solvent model predicted one predominant conformer for 1-3,
      featuring two inverse gamma-turns. The ECD spectra in ACN of 1 and 2 are
      characterized by a negative n-->pi* band near 230 nm and a positive pi-->pi* band
      below 200 nm with a long wavelength shoulder. The ECD spectra in TFE of 1-3 show
      similar spectra with blue-shifted bands. The VCD spectra in ACN-d(3) of 1 and 2
      show a +/-/+/- amide I sign pattern resulting from four uncoupled vibrations in
      the case of 1 and a sequence of two positive couplets in the case of 2. A -/+/+/-
      amide I VCD pattern was measured for 3 in TFE-d(2). All three peptides give a
      positive couplet or couplet-like feature (+/-) in the amide II region. VCD
      spectroscopy, in agreement with theoretical calculations revealed that low
      frequency amide I vibrations (at approximately 1630 cm(-1) or below) are
      indicative of a C(7) H-bonded inverse gamma-turns with Pro in position 2, while
      gamma-turns encompassing Ala absorb at higher frequency (above 1645 cm(-1)).

PMID- 20155824
TI  - Decreased lymphatic vessel counts in patients with systemic sclerosis:
      association with fingertip ulcers.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease that is
      characterized by microvascular disease and tissue fibrosis. Progressive loss and
      irregular architecture of the small blood vessels are well characterized, but the
      potential involvement of the lymphatic vessel system has not been analyzed
      directly in SSc. This study was undertaken to assess whether the lymphatic
      vascular system is affected in SSc, and whether changes to the lymphatic vessels
      are associated with dystrophic changes and tissue damage in patients with SSc.
      METHODS: Lymphatic endothelial cells in skin biopsy samples from patients with
      SSc and age- and sex-matched healthy volunteers were identified by staining for
      podoplanin and prox-1, both of which are specifically expressed in lymphatic
      endothelial cells but not in blood vascular endothelial cells. CD31 was used as a
      pan-endothelial cell marker. Statistical analyses were performed using Kruskal
      Wallis, Mann-Whitney U, and Spearman's rank correlation tests. RESULTS: The
      numbers of podoplanin- and prox-1-positive lymphatic vessels were significantly
      reduced in patients with SSc as compared with healthy individuals. The number of
      podoplanin-positive lymphatic precollector vessels was significantly lower in SSc
      patients with fingertip ulcers than in SSc patients without ulcers. Moreover, the
      number of lymphatic vessels correlated inversely with the number of fingertip
      ulcers at the time of biopsy and with the number of fingertip ulcers per year.
      The inverse correlation between lymphatic precollector vessel counts and
      fingertip ulcers remained significant after statistical adjustment for the blood
      vessel count, age, and modified Rodnan skin thickness score. CONCLUSION: These
      results demonstrate a severe reduction in the number of lymphatic capillaries and
      lymphatic precollector vessels in patients with SSc. Patients with decreased
      lymphatic vessel counts may be at particularly high risk of developing fingertip
      ulcers.

PMID- 20155825
TI  - Clinical images: Calcific iliopsoas bursitis in a patient with scleroderma
      mimicking avascular hip osteonecrosis.

PMID- 20155826
TI  - Combination antibiotics for Chlamydia-induced arthritis: breakthrough to a cure?

PMID- 20155827
TI  - Do rheumatoid arthritis and lymphoma share risk factors?: a comparison of
      lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA), in particular those with the
      most severe disease, are at increased risk of developing malignant lymphoma.
      Whether this increase is entirely a consequence of the RA disease and/or its
      treatment or is reflective of shared susceptibility to the two diseases remains
      unclear. We undertook this study to assess whether patients with RA are already
      at increased risk of lymphoma or of other cancers before the diagnosis of RA, and
      if the relative risk increases with time since RA diagnosis. METHODS: Patients
      with incident RA (symptom duration <1 year) (n = 6,745) registered in the Swedish
      Early Arthritis Registry from 1997 through 2006 were identified. For each
      patient, 5 general population controls were randomly matched by sex, age, marital
      status, and residence (n = 33,657). For all study subjects, inclusion in the
      nationwide Swedish Cancer Register in 1958-2006 was determined. Relative risks
      (RRs) (with 95% confidence intervals [95% CIs]) of lymphoma and of cancer
      overall, before and after diagnosis of RA, were estimated using conditional
      logistic regression and Cox regression, respectively. RESULTS: Before diagnosis
      of RA, there was no observed increase in the risk of lymphoma (RR [odds ratio]
      0.67 [95% CI 0.37-1.23]) or other cancers (RR 0.78 [95% CI 0.70-0.88]). During
      the first 10 years following diagnosis of RA, the overall RR (hazard ratio) of
      lymphoma development was 1.75 (95 % CI 1.04-2.96). CONCLUSION: These findings
      indicate that overall, a history of cancer, including lymphoma, does not increase
      the risk of subsequent RA development. Shared susceptibility to RA and lymphoma
      may thus be of limited importance. In contrast, increased lymphoma risks were
      observed within the first decade following RA diagnosis.

PMID- 20155828
TI  - Regulation of myeloperoxidase-specific T cell responses during disease remission
      in antineutrophil cytoplasmic antibody-associated vasculitis: the role of Treg
      cells and tryptophan degradation.
AB  - OBJECTIVE: T lymphocytes have been implicated in the pathogenesis of
      antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Patients with
      myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) experience
      relapses less frequently than those with proteinase 3 ANCA, suggesting greater
      immune regulation. This study was undertaken to investigate MPO-specific T cell
      reactivity during disease remission and the factors regulating their
      responsiveness. METHODS: MPO-specific T cells were quantified by enzyme-linked
      immunospot assay with additional Treg cell depletion or exogenous interleukin-2.
      Serum tryptophan and its metabolites were measured. In vivo blockade of
      indoleamine 2,3-dioxygenase (IDO) was performed, and its effect on MPO reactivity
      was assessed. RESULTS: During disease remission, MPO-specific interferon-gamma
      producing T cell frequencies were comparable with those found in healthy controls
      and significantly lower than those found in patients with acute disease.
      CD4+CD25+ regulatory cells did not play a role in maintaining these low MPO
      specific T cell frequencies, since depletion of Treg cells did not augment MPO
      specific responses, and FoxP3 levels were diminished in patients compared with
      controls. Treg cell function, however, was comparable in patients and controls,
      suggesting numerical rather than functional deficiency. We found diminished serum
      tryptophan levels and elevated levels of its metabolite kynurenine in patients
      with MPO AAV as compared with controls. To confirm the effect of tryptophan
      degradation on MPO responses in vivo, we inhibited degradation in MPO-immunized
      WKY rats and found greater immune responsiveness to MPO and a tendency to more
      severe glomerulonephritis. CONCLUSION: Our findings indicate that MPO-specific T
      cell frequencies are regulated during disease remission in association with
      tryptophan degradation. The tryptophan regulatory pathway is induced during
      active disease and persists during disease remission.

PMID- 20155829
TI  - Assessment of cognitive function in systemic lupus erythematosus, rheumatoid
      arthritis, and multiple sclerosis by computerized neuropsychological tests.
AB  - OBJECTIVE: Computerized neuropsychological testing may facilitate screening for
      cognitive impairment in systemic lupus erythematosus (SLE). This study was
      undertaken to compare patients with SLE, patients with rheumatoid arthritis (RA),
      and patients with multiple sclerosis (MS) with healthy controls using the
      Automated Neuropsychological Assessment Metrics (ANAM). METHODS: Patients with
      SLE (n = 68), RA (n = 33), and MS (n = 20) were compared with healthy controls (n
      = 29). Efficiency of cognitive performance on 8 ANAM subtests was examined using
      throughput (TP), inverse efficiency (IE), and adjusted IE scores. The latter is
      more sensitive to higher cognitive functions because it adjusts for the impact of
      simple reaction time on performance. The results were analyzed using O'Brien's
      generalized least squares test. RESULTS: Control subjects were the most efficient
      in cognitive performance. MS patients were least efficient overall (as assessed
      by TP and IE scores) and were less efficient than both SLE patients (P = 0.01)
      and RA patients (P < 0.01), who did not differ. Adjusted IE scores were similar
      between SLE patients, RA patients, and controls, reflecting the impact of simple
      reaction time on cognitive performance. Thus, 50% of SLE patients, 61% of RA
      patients, and 75% of MS patients had impaired performance on >or=1 ANAM subtest.
      Only 9% of RA patients and 11% of SLE patients had impaired performance on >or=4
      subtests, whereas this was true for 20% of MS patients. CONCLUSION: ANAM is
      sensitive to cognitive impairment. While such computerized testing may be a
      valuable screening tool, our results emphasize the lack of specificity of slowed
      performance as a reliable indicator of impairment of higher cognitive function in
      SLE patients.

PMID- 20155830
TI  - Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a
      population-based study.
AB  - OBJECTIVE: Interstitial lung disease (ILD) has been recognized as an important
      comorbidity in rheumatoid arthritis (RA). We undertook the current study to
      assess incidence, predictors, and mortality of RA-associated ILD. METHODS: We
      examined a population-based incidence cohort of patients with RA and a matched
      cohort of individuals without RA. All subjects were followed up longitudinally.
      The lifetime risk of ILD was estimated. Cox proportional hazards models were used
      to compare the incidence of ILD between cohorts, to investigate predictors, and
      to explore the impact of ILD on survival. RESULTS: Patients with RA (n = 582) and
      subjects without RA (n = 603) were followed up for a mean of 16.4 and 19.3 years,
      respectively. The lifetime risk of developing ILD was 7.7% for RA patients and
      0.9% for non-RA subjects. This difference translated into a hazard ratio (HR) of
      8.96 (95% confidence interval [95% CI] 4.02-19.94). The risk of developing ILD
      was higher in RA patients who were older at the time of disease onset, in male
      patients, and in individuals with more severe RA. The risk of death for RA
      patients with ILD was 3 times higher than in RA patients without ILD (HR 2.86
      [95% CI 1.98-4.12]). Median survival after ILD diagnosis was only 2.6 years. ILD
      contributed approximately 13% to the excess mortality of RA patients when
      compared with the general population. CONCLUSION: Our results emphasize the
      increased risk of ILD in patients with RA. The devastating impact of ILD on
      survival provides evidence that development of better strategies for the
      treatment of ILD could significantly lower the excess mortality among individuals
      with RA.

PMID- 20155831
TI  - Clinical images: Pachydermoperiostosis.

PMID- 20155832
TI  - ERK-1/2 and p38 in the regulation of hypertrophic changes of normal articular
      cartilage chondrocytes induced by osteoarthritic subchondral osteoblasts.
AB  - OBJECTIVE: Previous studies have shown the influence of subchondral bone
      osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes
      (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms
      involved during this process remain elusive, in particular, the signal
      transduction pathways. The aim of this study was to investigate the in vitro
      effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the
      potential involvement of MAPK signaling pathways during this process. METHODS:
      Normal and arthritic cartilage and bone samples were collected for isolation of
      ACCs and SBOs. Direct and indirect coculture models were applied to study
      chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation
      of the cell-cell interactions were monitored by phosphorylated antibodies and
      relevant inhibitors. RESULTS: OA SBOs led to increased hypertrophic gene
      expression and matrix calcification in ACCs by means of both direct and indirect
      cell-cell interactions. In this study, we demonstrated for the first time that OA
      SBOs suppressed p38 phosphorylation and induced ERK-1/2 signal phosphorylation in
      cocultured ACCs. The ERK-1/2 pathway inhibitor PD98059 significantly attenuated
      the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38
      inhibitor SB203580 resulted in the up-regulation of hypertrophic genes in ACCs.
      CONCLUSION: The findings of this study suggest that the pathologic interaction of
      OA SBOs and ACCs is mediated via the activation of ERK-1/2 phosphorylation and
      deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of
      ACCs.

PMID- 20155833
TI  - Transcription of proteinase 3 and related myelopoiesis genes in peripheral blood
      mononuclear cells of patients with active Wegener's granulomatosis.
AB  - OBJECTIVE: Wegener's granulomatosis (WG) is a systemic inflammatory disease that
      is associated with substantial morbidity. The aim of this study was to understand
      the biology underlying WG and to discover markers of disease activity that would
      be useful for prognosis and treatment guidance. METHODS: Gene expression
      profiling was performed using total RNA from peripheral blood mononuclear cells
      (PBMCs) and granulocyte fractions from 41 patients with WG and 23 healthy control
      subjects. Gene set enrichment analysis (GSEA) was performed to search for
      candidate WG-associated molecular pathways and disease activity biomarkers.
      Principal components analysis was used to visualize relationships between
      subgroups of WG patients and controls. Longitudinal changes in proteinase 3 (PR3)
      gene expression were evaluated using reverse transcription-polymerase chain
      reaction, and clinical outcomes, including remission status and disease activity,
      were determined using the Birmingham Vasculitis Activity Score for WG (BVAS-WG).
      RESULTS: Eighty-six genes in WG PBMCs and 40 in WG polymorphonuclear neutrophils
      (PMNs) were significantly up-regulated relative to controls. Genes up-regulated
      in WG PBMCs were involved in myeloid differentiation, and these included the WG
      autoantigen PR3. The coordinated regulation of myeloid differentiation genes was
      confirmed by GSEA. The median expression values of the 86 up-regulated genes in
      WG PBMCs were associated with disease activity (P = 1.3 x 10(-4)), and WG
      patients with low-level expression of the WG signature genes showed expression
      profiles that were only modestly different from that in healthy controls (P =
      0.07). PR3 transcription was significantly up-regulated in WG PBMCs (P = 1.3 x
      10(-5), false discovery rate [FDR] 0.002), but not in WG PMNs (P = 0.03, FDR
      0.28), and a preliminary longitudinal analysis showed that the fold change in PR3
      RNA levels in WG PBMCs corresponded to changes in the BVAS-WG score over time.
      CONCLUSION: Transcription of PR3 and related myeloid differentiation genes in
      PBMCs may represent novel markers of disease activity in WG.

PMID- 20155834
TI  - Antiinflammatory effects of tumor necrosis factor on hematopoietic cells in a
      murine model of erosive arthritis.
AB  - OBJECTIVE: To investigate the mechanisms leading to the influx of inflammatory
      hematopoietic cells into the synovial membrane and the role of tumor necrosis
      factor receptor I (TNFRI) and TNFRII in this process in an animal model of
      rheumatoid arthritis (RA). METHODS: We performed bone marrow transplantations in
      human TNF-transgenic mice using hematopoietic cells from wild-type, TNFRI(-/-),
      TNFRII(-/-), and TNFRI/II(-/-) mice as donors and assessed the severity of
      arthritis histologically. Generation of osteoclasts from the different genotypes
      was analyzed in vitro and in vivo. Apoptosis was analyzed using annexin V
      staining as well as TUNEL assays. RESULTS: Despite lacking responsiveness to TNF
      in their hematopoietic compartment, mice not only developed full-blown erosive
      arthritis but even showed increased joint destruction when compared with mice
      with a TNF-responsive hematopoietic compartment. We demonstrated different roles
      of the 2 different TNFRs in the regulation of these processes. The absence of
      TNFRI on hematopoietic cells did not affect joint inflammation but markedly
      attenuated erosive bone destruction via reduced synovial accumulation of
      osteoclast precursors. In contrast, the absence of TNFRII on hematopoietic cells
      increased joint inflammation as well as erosive bone destruction via the
      regulation of osteoclast precursor apoptosis. CONCLUSION: Our findings indicate
      that selective blockade of TNFRI, leaving the antiinflammatory effects of TNFRII
      unaltered instead of unselectively blocking TNF, might be advantageous in
      patients with RA.

PMID- 20155836
TI  - Relationship of asymmetric dimethylarginine and homocysteine to vascular aging in
      systemic lupus erythematosus patients.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is independently associated with
      accelerated atherosclerosis and premature arterial stiffening. Asymmetric
      dimethylarginine (ADMA) and homocysteine are mechanistically interrelated
      mediators of endothelial dysfunction and correlates of atherosclerosis in the
      general population. The aim of this study was to assess the relationship of ADMA
      and homocysteine to subclinical vascular disease in patients with SLE. METHODS:
      One hundred twenty-five patients with SLE who were participating in a study of
      cardiovascular disease underwent clinical and laboratory assessment, carotid
      artery ultrasonography to detect atherosclerosis, and radial artery applanation
      tonometry to measure arterial stiffness. RESULTS: Neither ADMA nor homocysteine
      correlated with the presence or extent of carotid atherosclerosis. In contrast,
      ADMA was significantly related to the arterial stiffness index. Independent
      correlates of arterial stiffening included the ADMA concentration, the presence
      of diabetes mellitus, older age at the time of diagnosis, longer disease
      duration, and the absence of anti-Sm or anti-RNP antibodies. A secondary
      multivariable analysis substituting homocysteine for ADMA demonstrated comparable
      relationships with arterial stiffness (r(2) = 0.616 for homocysteine and r(2) =
      0.595 for ADMA). CONCLUSION: ADMA and homocysteine are biomarkers for and may be
      mediators of premature arterial stiffening in patients with SLE. Because arterial
      stiffness has independent prognostic value for cardiovascular morbidity and
      mortality, its predictors may identify patients who are at increased risk of
      cardiovascular disease.

PMID- 20155835
TI  - Osteopontin deficiency impairs wear debris-induced osteolysis via regulation of
      cytokine secretion from murine macrophages.
AB  - OBJECTIVE: To investigate the molecular mechanisms underlying particle-induced
      osteolysis, we focused on osteopontin (OPN), a cytokine and cell-attachment
      protein that is associated with macrophage chemoattractant and osteoclast
      activation. METHODS: We compared OPN protein levels in human periprosthetic
      osteolysis tissues with those in osteoarthritis (OA) synovial tissues. To
      investigate the functions of OPN during particle-induced osteolysis in vivo,
      titanium particles were implanted onto the calvaria of OPN-deficient mice and
      their wild-type (WT) littermates. Mice were killed on day 10 and evaluated
      immunohistologically. The effects of OPN deficiency on the secretion of
      inflammatory cytokines were examined using cultured bone marrow-derived
      macrophages (BMMs). BMMs from OPN-deficient and WT mice were cultured with
      titanium particles for 12 hours, and the concentrations of inflammatory cytokines
      in the conditioned media were measured by enzyme-linked immunosorbent assay.
      RESULTS: Expression of OPN protein was enhanced in human periprosthetic
      osteolysis tissues as compared with OA synovial tissues. In the particle-induced
      model of osteolysis of the calvaria, bone resorption was significantly suppressed
      by OPN deficiency via inhibition of osteoclastogenesis, whereas an inflammatory
      reaction was observed regardless of the genotype. Results of immunostaining
      indicated that OPN protein was highly expressed in the membrane and bone surface
      at the area of bone resorption in WT mice. When BMMs were exposed to titanium
      particles, the concentration of proinflammatory cytokines, such as tumor necrosis
      factor alpha, interleukin-1alpha (IL-1alpha), IL-1beta, and IL-6, as well as
      chemotactic factors, such as monocyte chemoattractant protein 1 and macrophage
      inflammatory protein 1alpha, in the conditioned medium were significantly reduced
      by OPN deficiency. Whereas phagocytic activity of BMMs was not attenuated by OPN
      deficiency, phagocytosis-mediated NF-kappaB activation was impaired in OPN
      deficient BMMs. These data indicated that OPN was implicated in the development
      of particle-induced osteolysis via the orchestration of pro-/antiinflammatory
      cytokines secreted from macrophages. CONCLUSION: OPN plays critical roles in wear
      debris-induced osteolysis, suggesting that OPN is a candidate therapeutic target
      for periprosthetic osteolysis.

PMID- 20155837
TI  - Clinical images: Dramatic amelioration of pneumatosis cystoides intestinalis in
      systemic sclerosis.

PMID- 20155838
TI  - Combination antibiotics as a treatment for chronic Chlamydia-induced reactive
      arthritis: a double-blind, placebo-controlled, prospective trial.
AB  - OBJECTIVE: Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are
      known triggers of reactive arthritis (ReA) and exist in a persistent
      metabolically active infection state in the synovium, suggesting that they may be
      susceptible to antimicrobial agents. The goal of this study was to investigate
      whether a 6-month course of combination antibiotics is an effective treatment for
      patients with chronic Chlamydia-induced ReA. METHODS: This study was a 9-month,
      prospective, double-blind, triple-placebo trial assessing a 6-month course of
      combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible
      patients had to be positive for C trachomatis or C pneumoniae by polymerase chain
      reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead
      of azithromycin; 2) azithromycin and rifampin plus placebo instead of
      doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin.
      The primary end point was the number of patients who improved by 20% or more in
      at least 4 of 6 variables without worsening in any 1 variable in both combination
      antibiotic groups combined and in the placebo group at month 6 compared with
      baseline. RESULTS: The primary end point was achieved in 17 of 27 patients (63%)
      receiving combination antibiotics and in 3 of 15 patients (20%) receiving
      placebo. Secondary efficacy end points showed similar results. Six of 27 patients
      (22%) randomized to combination antibiotics believed that their disease went into
      complete remission during the trial, whereas no patient in the placebo arm
      achieved remission. Significantly more patients in the active treatment group
      became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse
      events were mild, with no significant differences between the groups. CONCLUSION:
      These data suggest that a 6-month course of combination antibiotics is an
      effective treatment for chronic Chlamydia-induced ReA.

PMID- 20155839
TI  - Inhibition of fibroblast activation protein and dipeptidylpeptidase 4 increases
      cartilage invasion by rheumatoid arthritis synovial fibroblasts.
AB  - OBJECTIVE: Since fibroblasts in the synovium of patients with rheumatoid
      arthritis (RA) express the serine proteases fibroblast activation protein (FAP)
      and dipeptidylpeptidase 4 (DPP-4)/CD26, we undertook the current study to
      determine the functional role of both enzymes in the invasion of RA synovial
      fibroblasts (RASFs) into articular cartilage. METHODS: Expression of FAP and DPP
      4/CD26 by RASFs was analyzed using fluorescence-activated cell sorting and
      immunocytochemistry. Serine protease activity was measured by cleavage of
      fluorogenic substrates and inhibited upon treatment with L-glutamyl L
      boroproline. The induction and expression of matrix metalloproteinases (MMPs) and
      tissue inhibitors of metalloproteinases (TIMPs) in RASFs were detected using real
      time polymerase chain reaction. Densitometric measurements of MMPs using
      immunoblotting confirmed our findings on the messenger RNA level. Stromal cell
      derived factor 1 (SDF-1 [CXCL12]), MMP-1, and MMP-3 protein levels were measured
      using enzyme-linked immunosorbent assay. The impact of FAP and DPP-4/CD26
      inhibition on the invasiveness of RASFs was analyzed in the SCID mouse
      coimplantation model of RA using immunohistochemistry. RESULTS: Inhibition of
      serine protease activity of FAP and DPP-4/CD26 in vitro led to increased levels
      of SDF-1 in concert with MMP-1 and MMP-3, which are downstream effectors of SDF-1
      signaling. Using the SCID mouse coimplantation model, inhibition of enzymatic
      activity in vivo significantly promoted invasion of xenotransplanted RASFs into
      cotransplanted human cartilage. Zones of cartilage resorption were infiltrated by
      FAP-expressing RASFs and marked by a significantly higher accumulation of MMP-1
      and MMP-3, when compared with controls. CONCLUSION: Our results indicate a
      central role for the serine protease activity of FAP and DPP-4/CD26 in protecting
      articular cartilage against invasion by synovial fibroblasts in RA.

PMID- 20155840
TI  - Atypical mRNA fusions in PML-RARA positive, RARA-PML negative acute promyelocytic
      leukemia.
AB  - Reciprocal RARA-PML transcripts are not detected in approximately 25% of patients
      with PML-RARA positive acute promyelocytic leukemia (APL), but the reasons for
      this are poorly understood. We studied 21 PML-RARA positive/RARA-PML negative
      cases by bubble PCR and multiplex long template PCR to identify the genomic
      breakpoints. Additional RT-PCR analysis was performed based on the DNA findings.
      Three cases were found to have complex rearrangements involving a third locus:
      the first had a PML-CDC6-RARA forward DNA fusion and expressed a chimeric PML
      CDC6-RARA mRNA in addition to a PML-RARA. The other two had HERC1-PML and
      NT_009714.17-PML genomic fusion sequences at their respective reciprocal
      breakpoints. Six patients were falsely classified as RARA-PML negative due to
      deletions on chromosome 15 and/or 17, or alternative splicing leading to atypical
      RARA-PML fusion transcripts, which were not identified by conventional RT-PCR
      assays. This study demonstrates that the frequency of RARA-PML expression has
      been underestimated and highlights remarkable complexity at chromosomal
      breakpoint regions in APL even in cases with an apparently simple balanced
      t(15;17)(q24;q12).

PMID- 20155841
TI  - Positioning of necrotic lobular intraepithelial neoplasias (LIN, grade 3) within
      the sequence of breast carcinoma progression.
AB  - Lobular intraepithelial neoplasia Grade 3 (LIN3) is a recently recognized variant
      of intraepithelial lobular neoplasia (LIN) of the breast composed of either
      uniform, generally small cells with massive lobular distension, pleomorphic
      cells, signet-ring cells, or any cell type with necrosis. In contrast to classic
      forms of LIN, there is no consensus on therapeutic strategies for LIN3. In part
      this is due to the paucity of molecular data that could assist in defining the
      relationship of LIN3 to classic LIN and carcinomas. In this study we have
      employed array comparative genomic hybridization to determine the patterns of
      chromosomal aberrations in nine LIN3 lesions. By comparison to array CGH data of
      13 classic LIN lesions, we demonstrate that classic LIN and LIN3 share several
      recurrent changes, in particular gains of 1q and losses of 16q. Both aberrations
      are known to appear early in tumorigenesis and to be associated with good
      prognosis. However, apart from this overlap, there were a number of karyotypic
      features that were observed exclusively in LIN3. Clearly, this lesion was
      characterized by a significantly higher number of DNA copy number changes (9 vs.
      31 on average), a considerable complexity of chromosomal rearrangements with more
      than 16 breakpoints in one chromosome and overlapping high copy amplifications
      encompassing a number of known oncogenes. Our data suggest that, at the genetic
      level, LIN3 represents a highly advanced lesion with considerable resemblance to
      carcinomas and, therefore, might represent the transition state from an
      intraepithelial neoplasm to breast carcinoma.

PMID- 20155842
TI  - Immunosuppressive effects via human intestinal dendritic cells of probiotic
      bacteria and steroids in the treatment of acute ulcerative colitis.
AB  - BACKGROUND: In ulcerative colitis (UC) gut bacteria drive inflammation. Bacterial
      recognition and T-cell responses are shaped by intestinal dendritic cells (DCs);
      therapeutic effects of probiotic bacteria may relate to modulation of intestinal
      DC. The probiotic mixture, VSL#3, increases interleukin (IL)-10 and downregulates
      IL-12p40 production by DC in vitro. We evaluated in vivo effects of oral VSL#3
      and steroids on colonic DC in patients with acute UC. METHODS: Rectal biopsies
      were obtained from patients with active UC before and after treatment with VSL#3,
      corticosteroids, or placebo, and from healthy controls. Myeloid colonic DC were
      studied from freshly isolated lamina propria cells using multicolor flow
      cytometry. Surface expression of activation markers, CD40, CD86, pattern
      recognition receptors, Toll-like receptor (TLR)-2 and TLR-4 were assessed.
      Changed function was measured from ongoing intracellular IL-10, IL-12p40, IL-6,
      and IL-13 production. RESULTS: Acute UC colonic myeloid DC were producing more IL
      10 and IL-12p40 than control DC (P = 0.01). In VSL#3-treated patients DC TLR-2
      expression decreased (P < 0.05), IL-10 production increased and IL-12p40
      production decreased (P < 0.005); 10/14 patients on VSL#3 showed a clinical
      response. Corticosteroids also resulted in increased IL-10 and reduced IL-12p40
      production by DC. Conversely, in patients on placebo, TLR-2 expression and
      intensity of staining for IL-12p40 and IL-6 increased (all P < 0.05); 5/14
      patients on placebo showed a clinical response (P = NS). CONCLUSIONS: Despite
      small numbers of human colonic DC available, we showed that treatment of UC
      patients with probiotic VSL#3 and corticosteroids induced "favorable" intestinal
      DC function in vivo, increasing regulatory cytokines and lowering proinflammatory
      cytokines and TLR expression. These effects may contribute to therapeutic
      benefit.

PMID- 20155843
TI  - Offspring from endogamic vs. exogamic matings: Absence of anthropometric
      differences among Sardinian children (Italy).
AB  - This study evaluates possible differences in body dimensions among children from
      matings of different exogamy levels. The cross-sectional sample consisted of 867
      children, 435 males, and 432 females, 6-10 years old, attending elementary
      schools in the metropolitan area of Cagliari, the capital of Sardinia (Italy).
      The children were divided into two groups according to the level of exogamy. The
      first group consisted of children of parents born in the same Sardinian
      municipality and was considered endogamous sensu stricto. The second group
      included children of parents born in municipalities from different Sardinian
      linguistic domains and was considered exogamous. The Mann-Whitney test did not
      reveal significant differences between the two groups of children in the mean
      rank values of the 36 anthropometric variables considered, with the exception of
      cephalic circumference in males and chest depth in females. In particular, there
      were no significant differences for anthropometric variables considered to be
      indirect indicators of nutritional status: sum of skinfolds, waist/hip ratio,
      body mass index, total upper arm area, upper arm muscle area, and upper arm fat
      area. The results indicate that Sardinian children from marriages of different
      exogamy levels do not differ in body dimensions if they grow up with similar
      nutritional and socioeconomic conditions.

PMID- 20155844
TI  - Dairy and milk consumption and child growth: Is BMI involved? An analysis of
      NHANES 1999-2004.
AB  - Humans are unique among mammals in that many consume cow's milk or other dairy
      products well beyond the traditional age of weaning. Milk provides various
      nutrients and bioactive molecules to support growth and development, and the
      question arises as to whether this dietary behavior influences growth parameters.
      There is evidence that milk makes positive contributions to growth in height, but
      its associations with other aspects of body size, such as body mass index (BMI),
      are not well-established. National Health and Nutrition Examination Survey
      (NHANES) data from 1999 to 2004 and multivariate regression analysis were used to
      test the hypothesis that milk (g) or total dairy product consumption (kJ) is
      associated with higher BMI percentile among US White, Black, and Mexican-American
      children of age 2-4 years (n = 1,493) and 5-10 years (n = 2,526). Younger
      children in the highest quartile of dairy intake had higher BMIs (beta = 7.5-8.0;
      P < 0.01) than those in the lowest two quartiles. Controlling for energy intake
      eliminated differences between QIV and QI. Among children of 5-10 years of age
      dairy intake had no relationship to BMI. Young children in the highest quartile
      of milk intake had higher BMIs than all lower quartiles (beta = 7.1-12.8; beta =
      6.3-11.8 in energy-controlled models; P < 0.05). Among children of 5-10 years of
      age, those in QIV for milk intake had higher BMIs than those in QII (beta = 8.3;
      beta = 7.1 in energy-controlled model; P < 0.01). Controlling for total protein
      or calcium did not change the results. Milk had more consistent positive
      associations with BMI than did dairy products, and these were strongest among
      children of 2-4 years of age.

PMID- 20155845
TI  - Video capsule endoscopy in inflammatory bowel disease: past, present, and future
      redux.
AB  - Over the last 8 years, capsule endoscopy (CE) has revolutionized the
      visualization of the small bowel. In 2004 this journal published "Capsule
      endoscopy in IBD: past, present and future" Kornbluth et al [2004] Inflamm Bowel
      Dis 10:278-285). In this article we review advances since that time and discuss
      whether CE has achieved its potential and what remaining goals it can and should
      hope to achieve. In the 2004 article we listed a series of clinical questions to
      be answered with regard to the use of capsule endoscopy We review those questions
      that have been addressed in the intervening 5 years, and also update those topics
      for which information was available at the time of the initial article.

PMID- 20155846
TI  - Thiopurine therapy in inflammatory bowel disease patients: analyses of two 8-year
      intercept cohorts.
AB  - BACKGROUND: Thiopurines have proven efficacy in long-term maintenance therapy of
      inflammatory bowel disease (IBD). Limited data are available with regard to
      factors predicting effectiveness and failure of long-term thiopurine use in IBD
      patients. METHODS: The data in this retrospective study are based on an 8-year
      intercept cohort of previous or present thiopurine-using IBD patients. Both
      cohorts are assessed by descriptive and statistical analysis aimed at determining
      thiopurine effectiveness and the variables that are predictive for failure of
      thiopurine therapy. RESULTS: In all, 363 IBD patients were included (60% female),
      63% with Crohn's disease and 33% with ulcerative colitis. Overall, thiopurines
      were continued in 145/363 (40%) and discontinued in 208/363 (57%) patients. The
      proportion of patients still using thiopurines at 3, 6, 12, 24, and 60 months was
      73%, 69%, 63%, 51%, and 42%, respectively. Patients discontinued thiopurines due
      to adverse events (39%), refractoriness (16%), and ongoing remission / patient's
      request (4%). 6-methylmercaptopurine (6-MMP) concentration and 6-MMP/6
      thioguanine nucleotides (6-TGN) ratio were significant higher in the failure
      group. Prolonged continuation of thiopurines was associated with a decreased risk
      of discontinuation. CONCLUSIONS: Azathioprine and 6-mercaptopurine were
      considered effective in approximately 40% of IBD patients after 5 years of
      treatment. A quarter of the patients discontinued thiopurines within 3 months,
      mostly due to adverse events. A high 6-MMP concentration or 6-MMP/6-TGN ratio was
      associated with therapeutic failure. If thiopurine use was successfully initiated
      in the first months, its use was usually extended over many years, as long-term
      use was associated with continuation of therapy.

PMID- 20155847
TI  - Photoperiod at conception predicts C677T-MTHFR genotype: A novel gene-environment
      interaction.
AB  - Data is presented, which suggest that the day length a woman experiences during
      the periconceptional period predicts the C677T-MTHFR genotype of her child.
      Logistic regression analysis involving 375 neonates born in the same geographical
      location within a three year period demonstrated that photoperiod (minutes) at
      conception predicts both genotype (P = 0.0139) and mutant allele carriage (P =
      0.0161); the trend clearly showing that the 677T-MTHFR allele frequency increases
      as photoperiod increases. We propose a number of explanations, including a
      hypothesis in which a long photoperiod around conception decreases maternal
      systemic folate because of UVA induced dermal oxidative degradation of 5-methyl
      H(4)folate, leading to a lower cellular 5,10-methylene-H(4)folate status. In this
      scenario, 5,10-methylene-H(4)folate would be more efficiently used for dTMP and
      DNA synthesis by 677T-MTHFR embryos than wildtype embryos giving the 677T-MTHFR
      embryos increased viability, and hence increasing mutant T-allele frequency.
      Alternate hypotheses include: increased seasonal availability of folate rich
      foods that genetically buffer any negative effect of 677T-MTHFR in embryos;
      seasonal oxidative stress lowering embryo-toxic homocysteine; an undefined
      hormonal effect of photoperiod on the neuroendocrine axis, which mediates
      genotype/embryo selection. The effect of photoperiod on genotype seems clear, but
      the speculative molecular mechanism underpinning the effect needs careful
      examination.

PMID- 20155848
TI  - Mechanisms by which inflammation may increase intestinal cancer risk in
      inflammatory bowel disease.
AB  - Patients with ulcerative colitis and Crohn's disease are at increased risk of
      developing intestinal cancers via mechanisms that remain incompletely understood.
      However, chronic inflammation and repeated events of inflammatory relapse in
      inflammatory bowel disease (IBD) expose these patients to a number of signals
      known to have tumorigenic effects including persistent activation of the nuclear
      factor-kappaB and cyclooxygenase-2/prostaglandin pathways, release of
      proinflammatory mediators such as tumor necrosis factor-alpha and interleukin-6,
      and enhanced local levels of reactive oxygen and nitrogen species. These
      inflammatory signals can contribute to carcinogenesis via 3 major processes: 1)
      by increasing oxidative stress, which promotes DNA mutagenesis thus contributing
      to tumor initiation; 2) by activating prosurvival and antiapoptotic pathways in
      epithelial cells, thereby contributing to tumor promotion; and 3) by creating an
      environment that supports sustained growth, angiogenesis, migration, and invasion
      of tumor cells, thus supporting tumor progression and metastasis. The present
      review integrates clinical and basic research observations in an attempt to
      provide a comprehensive understanding of how inflammatory processes may
      contribute to intestinal cancer development in IBD patients.

PMID- 20155849
TI  - Preliminary evidence supporting a framework of psychological adjustment to
      inflammatory bowel disease.
AB  - BACKGROUND: Adjustment to chronic disease is a multidimensional construct
      described as successful adaptation to disease-specific demands, preservation of
      psychological well-being, functional status, and quality of life. Inflammatory
      bowel disease (IBD) can be particularly challenging due to the unpredictable,
      relapsing and remitting course of the disease. METHODS: All participants were
      patients being treated in an outpatient gastroenterology clinic at a university
      medical center. Participants completed a survey of questionnaires assessing
      illness perceptions, stress, emotional functioning, disease acceptance, coping,
      disease impact, and disease-specific and health-related quality of life.
      Adjustment was measured as a composite of perceived disability, psychological
      functioning, and disease-specific and health-related quality of life. RESULTS:
      Participants were 38 adults with a diagnosis of either Crohn's disease (45%) or
      ulcerative colitis (55%). We observed that our defined adjustment variables were
      strongly correlated with disease characteristics (r = 0.33-0.80, all P < 0.05),
      an emotional representation of illness (r = 0.44-0.58, P < 0.01), disease
      acceptance (r = 0.34-0.74, P < 0.05), coping (r = 0.33-0.60, P < 0.05), and
      frequency of gastroenterologist visits (r = 0.39-0.70, P < 0.05). Better
      adjustment was associated with greater bowel and systemic health, increased
      activities engagement and symptom tolerance, less pain, less perceived stress,
      and fewer gastroenterologist visits. All adjustment variables were highly
      correlated (r = 0.40-0.84, P < 0.05) and demonstrated a cohesive composite.
      CONCLUSIONS: The framework presented and results of this study underscore the
      importance of considering complementary pathways of disease management including
      cognitive, emotional, and behavioral factors beyond the traditional medical and
      psychological (depression and anxiety) components.

PMID- 20155850
TI  - Effects of T cell-induced colonic inflammation on epithelial barrier function.
AB  - BACKGROUND: Epithelial barrier disturbance is thought to contribute to the
      pathogenesis of inflammatory bowel diseases; however, it remains unclear whether
      it is a primary defect participating to the onset of inflammation or only a
      consequence of sustained inflammation. METHODS: A time course study of epithelial
      barrier functions and immune mediators was performed in the CD4(+)CD45RB(hi) T
      cell transfer model of colitis using Ussing chambers. RESULTS: In
      nonreconstituted severe combined immunodeficiency (SCID) mice, no epithelial
      dysfunction was observed. However, after transfer of CD4(+)CD45RB(hi) T cells or
      total CD4(+) T cells, colon of SCID mice displayed a decreased epithelial
      resistance, even before overt microscopic inflammation had occurred. Sustained
      colitis of CD4(+)CD45RB(hi) T cell reconstituted mice was also associated with
      enhanced subepithelial resistance, enhanced paracellular permeability, and
      decreased net ion transport. All these reflect a disturbance of barrier function
      and may contribute to diarrhea. Epithelial resistance was positively correlated
      with interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta) levels
      and net ion transport inversely correlated with tumor necrosis factor alpha (TNF
      alpha) levels, pointing to the protective effect of IL-10 and TGF-beta and to a
      damaging effect of TNF-alpha. Indomethacin, a nonselective COX inhibitor,
      decreased epithelial resistance independent of T cells and inflammation, but its
      effect was more pronounced in inflamed colon. CONCLUSIONS: Induction of colitis
      by transfer of CD4(+)CD45RB(hi) T cells in SCID mice leads to changes in the
      colonic epithelium before colitis develops. Decreased epithelium resistance might
      contribute to the development of colitis; however, it is not sufficient to lead
      to chronic inflammation.

PMID- 20155851
TI  - NOD2 status and human ileal gene expression.
AB  - BACKGROUND: NOD2 single nucleotide polymorphisms have been associated with
      increased risk of ileal Crohn's disease (CD). This exploratory study was
      conducted to compare ileal mucosal gene expression in CD patients with and
      without NOD2 risk alleles. METHODS: Ileal samples were prospectively collected
      from 18 nonsmoking CD patients not treated with anti-TNF-alpha biologics and 9
      nonsmoking control patients without inflammatory bowel disease undergoing initial
      resection and genotyped for the 3 major NOD2 risk alleles (Arg702Trp, Gly908Arg,
      Leu1007fs). Microarray analysis was performed in samples from 4 NOD2(R) (at least
      1 risk allele) CD patients, 4 NOD2(NR) (no risk alleles) CD patients, and 4
      NOD2(NR) controls. Candidate genes selected by significance analysis of
      microarrays (SAM) were confirmed by quantitative reverse transcriptase polymerase
      chain reaction (qRT-PCR) assays of all the samples. RESULTS: SAM detected
      upregulation of 18 genes in affected ileum in NOD2(R) compared to NOD2(NR) CD
      patients, including genes related to lymphocyte activation. SAM also detected
      altered ileal gene expression in unaffected NOD2(NR) ileal mucosal CD samples
      compared to NOD2(NR) control samples. qRT-PCR conducted on all the samples
      confirmed that increased CD3D expression in affected samples was associated with
      NOD2(R) status, and that increased MUC1, DUOX2, DMBT1 and decreased C4orf7
      expression in unaffected samples was associated with CD, independent of NOD2
      status. CONCLUSIONS: The results support the concept that NOD2 risk alleles
      contribute to impaired regulation of inflammation in the ileum. Furthermore,
      altered ileal gene expression, independent of NOD2 status, is detected in the
      unaffected proximal margin of resected ileum from CD patients.

PMID- 20155852
TI  - Immaturity associated antigens are lost during induction for T cell lymphoblastic
      leukemia: implications for minimal residual disease detection.
AB  - BACKGROUND: Induction chemotherapy for acute leukemia often leads to antigenic
      shifts in residual abnormal blast populations. Studies in precursor B cell ALL (B
      ALL) have demonstrated that chemotherapy commonly results in the loss of antigens
      associated with immaturity, limiting their utility for minimal residual disease
      (MRD) detection. Little information is available about the stability of these
      antigens in precursor T cell ALL (T-ALL) though it is presumed that CD99 and
      terminal deoxynucleotidyl transferase (TdT) are highly informative based on
      limited studies. METHODS: In a longitudinal investigation, we explored patterns
      of lineage specific and immaturity-associated antigens in T-ALL in a large cohort
      of patients treated under the multicenter Children's Oncology Group (COG)
      protocol. All samples were analyzed using multicolor flow cytometry in a
      standardized fashion at a single institution. RESULTS: We report that markers of
      immaturity particularly, TdT and CD99, dramatically decline on leukemic blasts
      during therapy. CD34 and CD10 expression is confined to a minority of
      pretreatment samples and is also not stable. In contrast, lineage-associated
      markers including CD2, CD3, CD4, CD5, CD7, and CD8 failed to show significant
      trends. CONCLUSIONS: Our study strongly argues for expansion of immunophenotyping
      panels for T-ALL MRD to decrease reliance on immature antigens. This study
      represents the first demonstration of consistent immunophenotypic shifts in T
      ALL.

PMID- 20155853
TI  - Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal
      plasma cell-related disorders.
AB  - In recent years, multiparameter flow cytometry (MFC) immunophenotyping has become
      mandatory in the clinical management of hematological malignancies, both for
      diagnostic and monitoring purposes. Multiple myeloma (MM) and other clonal plasma
      cell-related (PC) disorders should be no exception to this paradigm, but
      incorporation of immunophenotypic studies in the management of patients with PC
      disorders is still far from being routinely established in many diagnostic flow
      cytometry laboratories. For clonal PC disorders, MFC is of clear and established
      clinical relevance in: (1) the differential diagnosis between MM and other PC
      related disorders; (2) the identification of high-risk MGUS and smoldering MM;
      (3) minimal residual disease investigation after therapy; additionally it may
      also be useful for (4) the definition of prognosis-associated antigenic profiles;
      and (5) the identification of new therapeutic targets. In this article, we review
      the clinical value of MFC in the study of PC disorders, with specific emphasis in
      those areas where consensus exists on the need to incorporate MFC into routine
      evaluation of MM and other clonal PC-related disorders.

PMID- 20155854
TI  - Implications of Cheyne-Stokes breathing in advanced systolic heart failure.
AB  - BACKGROUND: Cheyne-Stokes breathing (CSB) has been associated with heart failure
      (HF) patients for many years; however, its true prevalence and its prognostic
      implications are still obscure. HYPOTHESIS: The goal of this study was to
      investigate the prevalence and the possible prognostic implications of nocturnal
      CSB in advanced heart failure patients. METHODS: We performed single night full
      polysomonography ambulatory sleep studies in 71 HF patients. We analyzed the
      patients' sleep studies, clinical and laboratory data, and 6 month mortality.
      RESULTS: A total of 71 chronic systolic HF patients were analyzed, 60 males, 11
      females, age 65 +/- 13 years. Mean left ventricular ejection fraction was 27% +/-
      11%. Short episodes of CSB (at least 3 min duration) were present in all
      patients, and mean CSB duration was 1 hour. CSB duration was associated
      significantly with both high serum levels of N-terminal prohormone brain
      natriuretic peptide (NT-proBNP) as well as with 6 month mortality. Log CSB time
      had a significant correlation with log NT-proBNP (r = 0.5, P<.0001). Based on
      median CSB duration, the Kaplan-Meier survival curve analysis showed significant
      association with 6 month mortality (P = .03). CONCLUSIONS: CSB prevalence in
      advanced HF patients is higher than previously reported and is associated with
      increased serum levels of NT-proBNP and higher 6 month mortality.

PMID- 20155856
TI  - Cardiac arrhythmia management using a noncontact mapping multielectrode array.
AB  - BACKGROUND: The multielectrode array (MEA) enables noncontact mapping of cardiac
      arrhythmias; our experience is reviewed and reported. HYPOTHESIS: The MEA has a
      role as first line therapy in multiple arrhythmias. METHODS: Retrospective and
      prospective analysis of all consecutive cases performed using the MEA over a 6
      year period. RESULTS: Electrophysiological study and catheter ablation, 46% under
      general anaesthesia, using radiofrequency (RF), cryothermal and low energy direct
      current (DC) was performed in 66 procedures on 31 females and 29 males, average
      age 50.2 yrs (19.3-81.6); 8 patients underwent multiple procedures. 24 patients
      (36%) had undergone past ablation for the same arrhythmia. A wide variety of
      arrhythmias from all chambers were treated, majority right atrial (56%) and right
      ventricular (29%). Procedural success was complete in 77.4% and
      partial/indeterminate in 11.3%, highest in right atrial tachycardia, right
      ventricular outflow tract ectopy and typical atrial flutter (79, 82 and 100%). RF
      energy was most commonly used (67%) and DC carried 100% success. Ablation was
      delivered at 'early activation' and 'breakout' in focal arrhythmias. In re
      entrant circuits linear ablation transecting path of activation extending to
      regions of functional/anatomic block was performed. Two of 7 complications were
      attributed to the MEA: groin haematomas. At mean 12.4 mo follow up 56% were
      arrhythmia free, 15% asymptomatic or minimally symptomatic and 12 patients had
      new arrhythmias. CONCLUSIONS: The MEA is effective, safe and suitable for first
      line therapy in multiple cardiac arrhythmias particularly in the right heart.
      Further study is warranted comparing it to other mapping techniques.

PMID- 20155857
TI  - Underuse of thrombolytic therapy in acute myocardial infarction and left bundle
      branch block.
AB  - Thrombolytic therapy reduces mortality in patients with acute myocardial
      infarction (AMI) and left bundle branch block (LBBB). The difficulty in
      accurately diagnosing AMI in patients with LBBB, however, might result in their
      undertreatment. Among 3,890 patients hospitalized with chest pain, 241 (6.2%) had
      LBBB at presentation. The only variable independently associated with AMI among
      patients with LBBB was in-hospital left ventricular failure (odds ratio [OR]:
      4.32, 95% confidence interval [CI]: 1.95-9.57, p < 0.0005). Only 16 (29%) of the
      LBBB patients with AMI received thrombolytic therapy compared with 583 (78%) of
      the 747 patients with ST-elevation AMI (p < 0.0005). A further 19 (10%) LBBB
      patients without AMI also received thrombolysis. Difficulty in making an accurate
      early diagnosis in patients with LBBB ensures that the majority of those with AMI
      fail to receive thrombolytic therapy while others without AMI are treated
      inappropriately. Improved diagnostic and therapeutic strategies are needed for
      patients with acute coronary syndromes and LBBB.

PMID- 20155855
TI  - Influence of gender on long-term prognosis of patients with chronic heart failure
      seen in heart failure clinics.
AB  - BACKGROUND: Controversy exists concerning the influence of gender in the
      prognosis of patients with heart failure and no evidence is available from
      specific heart failure clinics. HYPOTHESIS: Women with ambulatory heart failure
      are managed differently than men, although their prognosis might be better than
      men. METHODS AND RESULTS: We analyzed the clinical characteristics, complementary
      test results, treatment, and prognosis in 4720 patients with chronic heart
      failure seen in 62 specialized clinics forming part of a multicenter registry
      during a mean follow-up of 40 months. The mean age was 65 +/- 12 years and 71%
      were men. The men were younger than the women and more often had a history of
      hyperlipidemia and ischemic heart disease. The men had a more advanced heart
      failure New York Heart Association (NYHA) functional class (III-IV) than the
      women and a greater frequency of systolic ventricular dysfunction. The men more
      often received treatment with beta-blockers, vasodilators, and antiplatelet
      aggregators as well as higher mean doses as compared with the women. The overall
      survival after the follow-up was similar for both genders, although the women had
      lower rates of survival free of admission for heart failure. CONCLUSIONS: Despite
      the mortality of women and men with heart failure being similar, the rate of
      readmission for heart failure is greater in women in specialized heart failure
      clinics. These results may be associated with the pharmacological treatment
      differences observed.

PMID- 20155858
TI  - The clinical significance of aspirin resistance in patients with chest pain.
AB  - BACKGROUND: There are conflicting data in the literature about the clinical
      significance of aspirin resistance. HYPOTHESIS: We aimed to prospectively
      evaluate the prevalence of biochemical aspirin resistance in patients on aspirin
      therapy who were admitted to the emergency clinic with chest pain. We also aimed
      to evaluate the relation between acute coronary syndromes (ACS) and aspirin
      resistance. METHODS: A total of 338 patients were included in the study. Platelet
      reactivity was measured with the PFA-100 system (Dade Behring Inc, Deerfield,
      IL). Aspirin resistance determined by the PFA-100 was defined as a normal
      collagen and/or epinephrine closure time despite aspirin treatment (<165 s).
      RESULTS: Patients were divided into 4 groups: stable angina pectoris (SAP),
      unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI), ST-elevation
      myocardial infarction (STEMI), and rule out ACS. Aspirin resistance was found in
      81 (24%) patients in all groups. Patients with ACS had significantly more aspirin
      resistance than patients with rule out ACS or patients with SAP (P < .001). In
      the SAP group, 31 (19.6%) patients; in the UA/NSTEMI group, 19 (35.8%) patients;
      in the STEMI group, 14 (50%) patients; and in the rule out ACS group, 17 (17.2%)
      patients had aspirin resistance (P < .001). In the multivariate analysis, cardiac
      biomarker elevation on admission to emergency department and platelet count
      appeared as independent factors predictive of aspirin resistance. CONCLUSIONS: We
      demonstrated that incidence of aspirin resistance was significantly higher in
      patients who were finally diagnosed as ACS, especially in aspirin-taking patients
      admitted to the emergency clinic with STEMI.

PMID- 20155859
TI  - Concomitant aortic dissection resulting in left main coronary transection.

PMID- 20155860
TI  - Characterization of nanoscale transformations in polyelectrolyte multilayers
      fabricated from plasmid DNA using laser scanning confocal microscopy in
      combination with atomic force microscopy.
AB  - Laser scanning confocal microscopy (LSCM) and atomic force microscopy (AFM) were
      used to characterize changes in nanoscale structure that occur when ultrathin
      polyelectrolyte multilayers (PEMs) are incubated in aqueous media. The PEMs
      investigated here were fabricated by the deposition of alternating layers of
      plasmid DNA and a hydrolytically degradable polyamine onto a precursor film
      composed of alternating layers of linear poly(ethylene imine) (LPEI) and sodium
      poly(styrene sulfonate) (SPS). Past studies of these materials in the context of
      gene delivery revealed transformations from a morphology that is smooth and
      uniform to one characterized by the formation of nanometer-scale particulate
      structures. We demonstrate that in-plane registration of LSCM and AFM images
      acquired from the same locations of films fabricated using fluorescently labeled
      polyelectrolytes allows the spatial distribution of individual polyelectrolyte
      species to be determined relative to the locations of topographic features that
      form during this transformation. Our results suggest that this physical
      transformation leads to a morphology consisting of a relatively less disturbed
      portion of film composed of polyamine and DNA juxtaposed over an array of
      particulate structures composed predominantly of LPEI and SPS. Characterization
      by scanning electron microscopy and energy-dispersive X-ray microanalysis
      provides additional support for this interpretation. The combination of these
      different microscopy techniques provides insight into the structures and dynamics
      of these multicomponent thin films that cannot be achieved using any one method
      alone, and could prove useful for the further development of these assemblies as
      platforms for the surface-mediated delivery of DNA.

PMID- 20155861
TI  - Doxazosin treatment alters stromal cell behavior and increases elastic system
      fibers deposition in rat prostate.
AB  - Doxazosin (DOX), an alpha-adrenoceptor antagonist, induces the relaxation of
      smooth muscle cell tonus and reduces the clinical symptoms of benign prostatic
      hyperplasia (BPH). However, the effects of DOX in the prostate stromal
      microenvironment are not fully known. In a previous study, we showed that DOX
      treatment for 30 days increased deposition of collagen fibers in the three rat
      prostatic lobes. Herein, we investigated the effects of DOX on stromal cell
      ultrastructure and elastic fiber deposition. Adult Wistar rats were treated with
      DOX (25 mg/kg/day); and the ventral, dorsal, and anterior prostates were excised
      at 30 days of treatment. The prostatic lobes were submitted to histochemical and
      stereological-morphometric analyze and transmission electron microscopy (TEM).
      Histochemical staining plus stereological analysis of the elastic fiber system
      showed that DOX-treated prostatic lobes presented more elaunin and elastic fibers
      than controls, mainly in the ventral lobe. Ultrastructural analysis showed that
      fibroblasts and smooth muscle cells from DOX-treated prostates presented active
      synthetic phenotypes, evidenced by enlarged rough endoplasmic reticulum and Golgi
      apparatus cisterns, and confirmed the observation of thickened elaunin fibers.
      Our findings suggest that, under alpha-adrenergic blockade by DOX, the
      fibroblasts become more active and smooth muscle cells shift from a predominantly
      contractile to a more synthetic phenotype. The deposition of collagen and elastic
      system fibers in the prostatic stroma may counterbalance the absence of smooth
      muscle tone during alpha-blockers treatment.

PMID- 20155862
TI  - Neurochemical biomarkers in the differential diagnosis of movement disorders.

PMID- 20155863
TI  - PDD-Short Screen: a brief cognitive test for screening dementia in Parkinson's
      disease.
AB  - The diagnosis of Parkinson's disease with dementia (PDD) is currently based on
      clinical criteria (DSM-IV, MDS-Task Force). In daily practice and research
      studies, these criteria still depend on the subjective impression of the
      examiner. Brief screening tests (BST) are helpful in identifying patients with PD
      with dementia, which can be difficult in patients with advanced PD. We aimed to
      develop a BST for PD, the PDD-Short Screen (PDD-SS), to accurately and quickly
      screen for PDD. In this prospective study, 70 patients with nondemented (age 73.8
      +/- 4.4) and 32 demented (age 73.8 +/- 4.4) PD regularly attending a Movement
      Disorders Clinic were included. Diagnosis of dementia was based on DSM-IV
      criteria, CDR score >or=1, and PD-CRS total score <or=64. The PDD-SS, Mattis
      Dementia Rating Scale (MDRS), and Mini-Mental State Examination (MMSE) were
      administered to all participants. Validity, reliability, and discriminative power
      of the PDD-SS were examined. The final version of the scale included the items
      immediate and delayed verbal memory, clock drawing, alternating verbal fluency,
      and a questionnaire covering cognitive and psychiatric (hallucinations, apathy)
      symptoms common in PDD. A cutoff score <or=11 on the PDD-SS yielded high
      sensitivity (89.8%) and specificity (88.5%) for diagnosing PDD. The MDRS
      displayed similar accuracy, but the PDD-SS administration time was significantly
      shorter (4.8-6.9 vs. 17.5-25.2 minutes). Diagnosis of dementia using the PDD-SS
      was not influenced by age, education, or motor function. The PDD-SS appears as
      the first BST for diagnosing PDD, displays an excellent diagnostic accuracy, and
      takes 5 to 7 minutes to be administered.

PMID- 20155864
TI  - Reply: neuropathy as a potential complication of levodopa use in Parkinson's
      disease: a pharmacological and pharmacovigilance point of view.

PMID- 20155866
TI  - Findings of misconduct in science.

PMID- 20155865
TI  - Ropinirole diminishes myoclonus and improves writing and postural balance in an
      ULD patient.

PMID- 20155868
TI  - Bill Pollin Era at NIDA (1979-1985).

PMID- 20155867
TI  - Increased access to psychological therapies.

PMID- 20155869
TI  - The road from ADAMHA to NIH: Reflections on NIDA (1992-1994).

PMID- 20155870
TI  - NIDA 35-year anniversary: Past lessons, present accomplishments and future
      challenges (2001-2003).

PMID- 20155871
TI  - The history of a public science: How the Addiction Research Center became the
      NIDA Intramural Research Program.

PMID- 20155872
TI  - NIDA, this is your life.

PMID- 20155873
TI  - HPV vaccination: time to end the debate.

PMID- 20155874
TI  - Telehealth innovations in health education and training.
AB  - Telehealth applications are increasingly important in many areas of health
      education and training. In addition, they will play a vital role in biomedical
      research and research training by facilitating remote collaborations and
      providing access to expensive/remote instrumentation. In order to fulfill their
      true potential to leverage education, training, and research activities,
      innovations in telehealth applications should be fostered across a range of
      technology fronts, including online, on-demand computational models for
      simulation; simplified interfaces for software and hardware; software frameworks
      for simulations; portable telepresence systems; artificial intelligence
      applications to be applied when simulated human patients are not options; and the
      development of more simulator applications. This article presents the results of
      discussion on potential areas of future development, barries to overcome, and
      suggestions to translate the promise of telehealth applications into a
      transformed environment of training, education, and research in the health
      sciences.

PMID- 20155875
TI  - ["Light" products cause obesity even more. US study: artificial sweeteners create
      hunger].

PMID- 20155876
TI  - [Role of F.F. Erisman in development of occupational hygiene].

PMID- 20155877
TI  - [Scientific basis for system evaluating and managing occupational risk in
      contemporary production and environment].
AB  - The authors gave scientific basis for system evaluating occupational risk and
      managing workers' health disorders, according to periodic medical examinations
      data, to ambient levels of environmental (including occupational) hazards,
      exemplified by industrial complex in Arkhangelsk city. This scientific basis
      helped to define categories and levels of occupational risk, etiologic share of
      hazards in disease development, index of occupational diseases, cause effect
      relationships of disease development and work conditions and other environmental
      factors, to specify management solutions on lowering occupational risk.

PMID- 20155878
TI  - Status of municipal solid waste management in   Hanoi, Vietnam.

PMID- 20155879
TI  - Present at the creation--NIDA's first five years.

PMID- 20155880
TI  - The highs and lows of my years at NIDA (1986-1992).

PMID- 20155881
TI  - NIDA in the 90s: (1994-2001).

PMID- 20155882
TI  - Celebrating the history of NIDA (2003-present).

PMID- 20155883
TI  - How NIDA became interested in precise nuances of injection behaviors.

PMID- 20155884
TI  - [Q & A. A case of a relatively large gallbladder polyp].

PMID- 20155885
TI  - [A thought on postgraduate psychiatric education from the viewpoint of residents
      in the latter stage of training based on the system of training of psychiatric
      specialists--the latter part of the psychiatric training at university
      hospitals].

PMID- 20155886
TI  - [Characteristics of the training system at the psychiatric hospitals in the
      framework of the National Hospital System--a viewpoint of young psychiatrists
      being trained without belonging to university medical departments].

PMID- 20155888
TI  - [Postgraduate psychiatric training in Japan].

PMID- 20155887
TI  - [Re-evaluation of the "road to becoming a psychiatrist"--learning from the
      interaction with young psychiatrists from overseas].

PMID- 20155889
TI  - [Cooperation with psychiatrists: a viewpoint of a nurse "in attendance"].

PMID- 20155890
TI  - [Cooperation between psychiatrists and pharmacists in chemotherapy conducted in
      psychiatry].

PMID- 20155891
TI  - [Report on a survey on psychiatric technology].

PMID- 20155892
TI  - [What is expected in psychiatry in psychiatric team care].

PMID- 20155893
TI  - Regio- and stereoselective synthesis of novel dispiropyrrolidine bisoxindole
      derivatives via multicomponent reactions.
AB  - A convenient and efficient method for the synthesis of novel dispiropyrrolidine
      bisoxindole derivatives by 1,3-dipolar cycloaddition reaction of azomethine
      ylides has been developed. The synthesis was achieved by using a one-pot
      multicomponent procedure. The features of this procedure were characterized by
      the following: mild reaction conditions, high yields, high regio- and
      stereoselectivity, one-pot procedure, and operational simplicity.

PMID- 20155894
TI  - Degenerate two-photon absorption in all-trans retinal: nonlinear spectrum and
      theoretical calculations.
AB  - In this work we investigate the degenerate two-photon absorption spectrum of all
      trans retinal in ethanol employing the Z-scan technique with femtosecond pulses.
      The two-photon absorption (2PA) spectrum presents a monotonous increase as the
      excitation wavelength approaches the one-photon absorption band and a peak at 790
      nm. We attribute the 2PA band to the mixing of states (1)B(u)(+)-like and |S(1)>,
      which are strongly allowed by one- and two-photon, respectively. We modeled the
      2PA spectrum by using the sum-over-states approach and obtained spectroscopic
      parameters of the electronic transitions to |S(1)>, |S(2)> ("(1)B(u)(+)"),
      |S(3)>, and |S(4)> singlet-excited states. The results were compared with
      theoretical predictions of one- and two-photon transition calculations using the
      response functions formalism within the density functional theory framework with
      the aid of the CAM-B3LYP functional.

PMID- 20155895
TI  - Importance of the lactate dehydrogenase quaternary structure in theoretical
      calculations.
AB  - Using the example of lactate dehydrogenase, we show that enzyme quaternary
      structure has an important influence on the structure of the active site and that
      models that comprise all amino acids in the vicinity of an active site, but are
      missing this structural information, can lead to incorrect results. We also show
      that binding isotope effects are very sensitive to the geometric parameters, and
      thus one should be very cautious when interpreting results obtained with models
      that are too coarse. In terms of the type of hydrogen bonds, our results indicate
      that binding isotope effects are pronounced only when a hydrogen bond exhibits
      some covalent character.

PMID- 20155897
TI  - Multifunctional porous graphene for nanoelectronics and hydrogen storage: new
      properties revealed by first principle calculations.
AB  - The lack of an obvious "band gap" is a formidable hurdle for making a
      nanotransistor from graphene. Here, we use density functional calculations to
      demonstrate for the first time that porosity such as evidenced in recently
      synthesized porous graphene (
      http://www.sciencedaily.com/releases/2009/11/091120084337.htm ) opens a band gap.
      The size of the band gap (3.2 eV) is comparable to most popular photocatalytic
      titania and graphitic C(3)N(4) materials. In addition, the adsorption of hydrogen
      on Li-decorated porous graphene is much stronger than that in regular Li-doped
      graphene due to the natural separation of Li cations, leading to a potential
      hydrogen storage gravimetric capacity of 12 wt %. In light of the most recent
      experimental progress on controlled synthesis, these results uncover new
      potential for the practical application of porous graphene in nanoelectronics and
      clean energy.

PMID- 20155898
TI  - Environmental behavior of the chiral aryloxyphenoxypropionate herbicide diclofop
      methyl and diclofop: enantiomerization and enantioselective degradation in soil.
AB  - In this study, the degradation of diclofop-methyl (DM) and its main metabolite,
      diclofop (DC), in two soils under aerobic and anaerobic conditions were
      investigated using enantioselective HPLC. Under aerobic or anaerobic conditions,
      rapid hydrolysis to the corresponding acid diclofop (DC)was observed. The results
      from this study revealed that the degradation of DM in the two soils is not
      enantioselective, and the calculated half-lives (t(1/2)) for the two soils were
      both less than 1 day. However, the degradation of DC in the two soils is
      enantioselective both under aerobic and anaerobic conditions, and the S-(-)-DC
      was preferentially degraded, resulting in relative enrichment of the R-(+)-form.
      The calculated t(1/2) values of the enantiomers of DC ranged between 8.7 and 43.3
      days for aerobic incubation experiments and between 14.7 and 77.0 days for
      anaerobic incubation experiments, respectively. The enantiopure S-(-)- and R-(+)
      DC were incubated under aerobic conditions, and it revealed significant
      enantiomerization with inversion of the S-(-)-enantiomer into R-(+)-enantiomer,
      and vice versa, and the S-(-)-DC showed a significantly higher inversion tendency
      than the R-(+)-DC.

PMID- 20155899
TI  - Arsenic mobilization in a seawater inundated acid sulfate soil.
AB  - Tidal seawater inundation of coastal acid sulfate soils can generate Fe- and
      S0(4)-reducing conditions in previously oxic-acidic sediments. This creates
      potential for mobilization of As during the redox transition. We explore the
      consequences for As by investigating the hydrology, porewater geochemistry, solid
      phase speciation, and mineralogical partitioning of As across two tidal fringe
      toposequences. Seawater inundation induced a tidally controlled redox gradient
      Maximum porewater As (~400 MUg/L) occurred in the shallow (<1 m), intertidal,
      redox transition zone between Fe-oxidizing and S0(4)-reducing conditions. Primary
      mechanisms of As mobilization include the reduction of solid-phase As(V) to
      As(lll), reductive dissolution of As(V)-bearing secondary Fe(lll) minerals and
      competitive anion desorption. Porewater As concentrations decreased in the zone
      of contemporary pyrite reformation. Oscillating hydraulic gradients caused by
      tidal pumping promote upward advection of As and Fe(2+)-enriched porewater in the
      intertidal zone, leading to accumulation of As(V)-enriched Fe(lll) (hydr)oxides
      at the oxic sediment-water interface. While this provides a natural reactive-Fe
      barrier, it does not completely retard the flux of porewater As to overtopping
      surface waters. Furthermore, the accumulated Fe minerals may be prone to future
      reductive dissolution. A conceptual model describing As hydro-geochemical
      coupling across an intertidal fringe is presented.

PMID- 20155900
TI  - Novel anion-tuning supramolecular gels with dual-channel response: reversible sol
      gel transition and color changes.
AB  - Two novel low-molecular-weight organogelators (LMOGs) 1 and 2 composed of an
      anthraquinone unit, a hydrazide group, and long alkyl chains were synthesized.
      They could form stable gels in wide tested solvents. Chloroalkanes and aromatic
      solvents tend to result in transparent gels, while alcohol and other solvents
      yield opaque gels. The FT-IR, PXRD, and (1)H NMR spectral studies revealed that
      hydrogen bonding and pi-pi interactions were the main driving forces for
      formation of the gels. Although the hydrazide unit and the anthraquinone group
      were connected by the sigma-bond, the chloroform gel of 1 could be changed into a
      red solution upon the addition of anion (F(-), AcO(-), and H(2)PO(4)(-)) due to
      the disruption of the intermolecular hydrogen-bondings. Moreover, the red color
      clearly faded at once and the solution regelated upon the addition of methanol.
      The results indicated that 1 and 2 as smart anion-responsive gel might provide
      the basis for the development of nonfluid systems for sensing anion with the
      naked eye.

PMID- 20155901
TI  - Structure and absolute configuration of karlotoxin-2, an ichthyotoxin from the
      marine dinoflagellate Karlodinium veneficum.
AB  - In an attempt to determine the cause of repeated fish kills in an estuarine
      aquaculture facility in Maryland, a toxin with hemolytic, cytotoxic, and
      ichthyotoxic properties, designated as karlotoxin-2 (KmTx2), was isolated from
      Karlodinium veneficum. The structure of KmTx2 was elucidated by means of detailed
      ID and 2D NMR spectra, including 2D INADEQUATE. The relative and absolute
      configurations of KmTx2 were determined using J-based configuration analysis and
      comparison of its degradation products with synthetic controls.

PMID- 20155903
TI  - Side-chain chi(1) conformations in urea-denatured ubiquitin and protein G from
      (3)J coupling constants and residual dipolar couplings.
AB  - Current NMR information on side-chain conformations of unfolded protein states is
      sparse due to the poor dispersion particularly of side-chain proton resonances.
      We present here optimized schemes for the detection of (3)J(HalphaHbeta),
      (3)J(NHbeta), and (3)J(C'Hbeta) scalar and (1)D(CbetaHbeta) residual dipolar
      couplings (RDCs) in unfolded proteins. For urea-denatured ubiquitin and protein
      G, up to six (3)J-couplings to (1)H(beta) are detected, which define the chi(1)
      angle at very high precision. Interpretation of the (3)J couplings by a model of
      mixed staggered chi(1) rotamers yields excellent agreement and also provides
      stereoassignments for (1)H(beta) methylene protons. For all observed amino acids
      with the exception of leucine, the chemical shift of (1)H(beta3) protons was
      found downfield from (1)H(beta2). For most residues, the precision of individual
      chi(1) rotamer populations is better than 2%. The experimental chi(1) rotamer
      populations are in the vicinity of averages obtained from coil regions in folded
      protein structures. However, individual variations from these averages of up to
      40% are highly significant and indicate sequence- and residue-specific
      interactions. Particularly strong deviations from the coil average are found for
      serine and threonine residues, an effect that may be explained by a weakening of
      side-chain to backbone hydrogen bonds in the urea-denatured state. The measured
      (1)D(CbetaHbeta) RDCs correlate well with predicted RDCs that were calculated
      from a sterically aligned coil model ensemble and the (3)J-derived chi(1) rotamer
      populations. This agreement supports the coil model as a good first approximation
      of the unfolded state. Deviations between measured and predicted values at
      certain sequence locations indicate that the description of the local backbone
      conformations can be improved by incorporation of the RDC information. The ease
      of detection of a large number of highly precise side-chain RDCs opens the
      possibility for a more rigorous characterization of both side-chain and backbone
      conformations in unfolded proteins.

PMID- 20155902
TI  - High-resolution 3D CANCA NMR experiments for complete mainchain assignments using
      C(alpha) direct detection.
AB  - The primary limitation of solution state NMR with larger, highly dynamic, or
      paramagnetic systems originates from signal losses due to fast transverse
      relaxation. This is related to the high gyromagnetic ratio gamma of protons,
      which are usually detected. Thus, it is attractive to consider detection of
      nuclei with lower gamma, such as (13)C, for extending the size limits of NMR.
      Here, we present an approach for complete assignment of C(alpha) and N resonances
      in fast relaxing proteins using a C(alpha) detected 3D CANCA experiment for
      perdeuterated proteins. The CANCA experiment correlates alpha carbons with the
      sequentially adjacent and succeeding nitrogen and alpha carbons. This enables
      elongation of the chain of assigned residues simply by navigating along both
      nitrogen and carbon dimensions using a "stairway" assignment procedure. The
      simultaneous use of both C(alpha) and N sequential connectivities makes the
      experiment more robust than conventional 3D experiments, which rely solely on a
      single (13)C indirect dimension for sequential information. The 3D CANCA
      experiment, which is very useful for mainchain assignments of higher molecular
      weight proteins at high magnetic field, also provides an attractive alterative
      for smaller proteins. Two versions of the experiment are described for samples
      that are (13)C labeled either uniformly or at alternate positions for removing
      one-bond (13)C-(13)C couplings. To achieve both high resolution and sensitivity,
      extensive nonuniform sampling was employed. Adding longitudinal relaxation
      enhancement agents can allow for shorter recycling delays, decreased measuring
      time, or enhanced sensitivity.

PMID- 20155904
TI  - Naphthalene Diels-Alder in a self-assembled molecular flask.
AB  - Despite its inertness toward pericyclic reactions under common conditions,
      naphthalenes readily undergo Diels-Alder reactions when coencapsulated with a
      suitable dienophile within the cavity of a self-assembled host. Localization of
      the reactant pair significantly reduces the entropic cost of the reaction, and
      preorganization within the host cavity controls both the regio- and
      stereoselectivity of the reaction: electronically disfavored exo adducts were
      obtained, and with substituted naphthalenes, the reaction takes place on the less
      electron-rich, unsubstituted ring. Our findings highlight the fact that judicious
      tuning of substrate size and shape within molecular flasks can unveil new and
      unusual reactivities for otherwise unreactive molecules.

PMID- 20155905
TI  - Boron esters as tunable anion carriers for non-aqueous batteries
      electrochemistry.
AB  - Compounds like LiF, Li(2)O, and Li(2)O(2) have considerable importance in
      batteries; the first two are ubiquitous in the protective SEI at the negative
      electrode, or the result of conversion reactions with fluorides and oxides. The
      latter, Li(2)O(2,) forms from oxygen reduction in the much vaunted Li/air
      batteries. Mastering their solubility in Li-based electrolytes is viewed as
      essential for further progress in battery safety, lifetime, or capacity. Aprotic
      solvents cannot provide the H-bonds necessary to their dissolution, and simple
      practical solutions have yet to materialize. Here we disclose a novel and large
      family of boron esters of general formula Y-C((CH(2)O)(Z(1)O)(Z(2)O))B whose
      Lewis acidity stems from geometrical constraint and can be tuned via electron
      affinity either by Y = CH(3) --> Y = NO(2) or Z(1,2) = CH(2) --> Z(1,2) = CO so
      as to partially or fully dissolve the above compounds both in battery solvent
      EC/DMC and in DMF. The extreme simplicity of synthesis and variability of these
      boron-based anion carriers, where the exchange rate is fast, are not only a
      valuable addition to coordination science but also a step forward to improve
      present battery systems.

PMID- 20155907
TI  - Main-chain ionic chiral polymers: synthesis of optically active quaternary
      ammonium sulfonate polymers and their application in asymmetric catalysis.
AB  - A condensation reaction between quaternary ammonium halide and sulfonate was
      first successfully applied to the synthesis of the chiral polymers. Reaction of
      bis(quaternary ammonium halide) with disulfonate afforded a polymer containing
      ionic bonds in its main chain. The chiral ionic polymers were applied to the
      asymmetric benzylation of N-diphenylmethylidene glycine tert-butyl ester to
      prepare (S)-phenylalanine derivatives in high yield with a high level of
      enantioselectivity.

PMID- 20155906
TI  - Diverted total synthesis leads to the generation of promising cell-migration
      inhibitors for treatment of tumor metastasis: in vivo and mechanistic studies on
      the migrastatin core ether analog.
AB  - A significantly simpler analog of the natural product migrastatin, termed
      migrastatin ether (ME), has been prepared and evaluated. Both in vivo and in
      vitro studies indicate that ME exhibits a concentration-dependent inhibitory
      effect on migration of breast cancer cells.

PMID- 20155908
TI  - Polyphenols, including the new Peapolyphenols A-C, from pea root exudates
      stimulate Orobanche foetida seed germination.
AB  - Three new polyphenols, named peapolyphenols A-C, together with an already well
      known polyphenol and a chalcone (1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4
      hydroxyphenyl)-1-propanone and 1-(2,4-dihydroxyphenyl)-3-(4
      methoxyphenyl)propenone) were isolated from pea root exudates. They were found to
      strongly stimulate Orobanche and Phelipanche species seed germination.
      Interestingly, only peapolyphenol A, 1,3,3-substituted propanone, and 1,3
      disubstituted propenone had specific stimulatory activity on O. foetida,
      excluding any other Orobanche or Phelipanche species tested. This species
      specificity is relevant, as O. foetida does not respond to the synthetic
      strigolactone analogue GR24, commonly used as a standard for germination assays.
      As characterized by spectroscopic methods, peapolyphenols A-C proved to be
      differently functionalized polyphenols with hydroxy and methoxy groups on both
      the aromatic rings and the propyl chain.

PMID- 20155909
TI  - Flavonoid composition and antioxidant activity of juices from Chinotto ( Citrus x
      myrtifolia Raf.) fruits at different ripening stages.
AB  - The qualitative and quantitative compositions of chinotto juice in two different
      maturation periods were determined via chromatographic separation of extracted
      aliquots of juice of Citrus x myrtifolia Raf. by using reverse-phase LC-DAD-ESI
      MS-MS. This provides a comprehensive chromatographic evaluation of 11 compounds
      (furanocoumarins and flavonoids C- and O-glycosides). Five flavonoids and two
      furanocoumarins were identified for the first time in chinotto juice: two C
      glucosides (vicenin-2 and lucenin-2 4'-methyl ether), two O-glycosides (narirutin
      and rhoifolin), and a 3-hydroxy-3-methylglutaryl flavanone (brutieridin).
      Bergapten and epoxybergamottin were the primary furanocoumarins found. Overall,
      the juice from immature chinotto fruits is richer in bioactive compounds than
      that obtained from ripe fruits. The free radical and superoxide anion scavenging
      activities of juice from both green and ripe fruits were assessed, and results
      showed that the former is much more efficient in scavenging radical and
      superoxide species than the latter.

PMID- 20155910
TI  - Analysis of cyromazine in poultry feed using the QuEChERS method coupled with LC
      MS/MS.
AB  - Cyromazine is used as an additive in poultry feed to inhibit the development of
      fly larvae in chicken manure. U.S. Environmental Protection Agency (EPA) method
      AG-555, modified from method AG-376, has been the standard method for cyromazine
      analysis in poultry feed. However, these methods are time-consuming (
      approximately 3 h) and require large volumes (200 mL) of solvent. This study
      developed an extraction procedure using the QuEChERS method that is faster (
      approximately 30 min) and uses 20 times less solvent than the AG-555 method.
      After extraction using the QuEChERS method, the extractant was subjected to
      cleanup using a C-18 solid phase extraction (SPE) followed by filtering through a
      0.45 microm syringe Teflon filter before the liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) analysis. Recovery of 75.0 +/- 6.2% was achieved. The
      method detection limit (MDL) and the limit of quantitation (LOQ) were 0.028 and
      0.094 ppm, respectively. Analyses of commercial poultry feed samples using the
      QuEChERS method yielded results similar to those obtained via EPA method AG-555.

PMID- 20155911
TI  - Improvement of water barrier property of paperboard by coating application with
      biodegradable polymers.
AB  - Biopolymeric coatings were prepared and applied onto paperboard to improve its
      water barrier property. To prepare whey protein isolate (WPI)/cellulose-based
      films, WPI and glycerol were dissolved in water with glutaraldehyde (cross
      linking agent) and cellulose xanthate. The solution was cast, dried, and
      insolubilized by entrapment of WPI in regenerated cellulose. Films were combined
      with beeswax (BW) into a bilayer coating system and then applied onto paperboard
      by heating compression. Another coating solution consisting of poly(vinyl
      butyral) (PVB)/zein was prepared by dissolving poly(vinyl alcohol) (PVA) and zein
      in 70% ethanol with glutaraldehyde and butyraldehyde (functionalization agent).
      The PVB/zein solution was applied onto paperboard after BW was sprayed. The
      structure of the PVB/zein-based coatings was analyzed by Fourier transform
      infrared spectroscopy (FTIR). The water vapor barrier property of coated
      paperboards was evaluated by water vapor transmission rate (WVTR) measurements.
      From the FTIR spectra, PVA functionalization after cross-linking and efficient
      acetalization into PVB were confirmed. WPI/cellulose and PVB/zein coating
      treatments improved the water barrier properties of paperboard by decreasing the
      WVTR by 77-78%. Although the BW coating was more efficient (decrease of WVTR by
      89%), bilayer coatings composed of BW and polymer coatings had a stronger barrier
      effect with a decrease of WVTR to 92-95%, hence approaching commercial attributes
      required to ensure water vapor barrier in paperboard-based food containers (10
      g/m(2).day). These results suggest that surface coating by biodegradable polymers
      may be utilized for the manufacture of paperboard containers in industrial
      applications.

PMID- 20155912
TI  - Differential inhibitory effects of conjugated linoleic acid isomers on mouse
      forestomach neoplasia induced by benzo(a)pyrene.
AB  - The differential anticarcinogenic activity of conjugated linoleic acid (CLA)
      isomers, including c9,t11-CLA, t10,c12-CLA, and t,t-CLA, was examined in a mouse
      forestomach carcinogenesis regimen induced by benzo(a)pyrene (BP). Female ICR
      mice (6-7 weeks of age, 26 +/- 1 g) were divided into six groups (30 mice/group,
      5 mice/cage): control, linoleic acid, CLA, c9,t11-CLA, t10,c12-CLA, and t,t-CLA.
      Each mouse was orally given 0.1 mL of sample and 0.1 mL of olive oil on Monday
      and Wednesday and BP (2 mg in 0.2 mL of olive oil) on Friday. This cycle was
      repeated four times. Twenty-three weeks later, the experiment was terminated for
      tumor analysis. t,t-CLA significantly reduced (p < 0.05) both tumor number and
      tumor size per mouse, relative to CLA and c9,t11-CLA, but similar to t10,c12-CLA.
      Reduction in tumor incidence by t,t-CLA (84.6%) was similar to that by CLA,
      c9,t11-CLA, and t10,c12-CLA, but it was significantly reduced (p < 0.05),
      relative to 100% linoleic acid and control. t,t-CLA elevated the apoptotic index
      to 35%, relative to 23% for CLA, 21% for c9,t11-CLA, 29% for t10,c12-CLA, 7% for
      linoleic acid, and 4% for control. t,t-CLA up-regulated the expression of the Bax
      gene and activated caspase-3 enzymes but down-regulated expression of the Bcl-2
      gene. Cytosolic phospholipase A(2) activity was not affected by the CLA isomers
      tested. These results suggest that t,t-CLA has superior anticarcinogenic
      potential on BP-induced mouse forestomach neoplasia to CLA, c9,t11-CLA, and
      t10,c12-CLA, via the induction of apoptosis through mitochondrial dysfunction.

PMID- 20155913
TI  - In vitro intestinal absorption of carotenoids delivered as molecular inclusion
      complexes with beta-cyclodextrin is not inhibited by high-density lipoproteins.
AB  - This study analyzed the assimilation efficiency of carotenoids when they are
      delivered as inclusion complexes with beta-cyclodextrin (CyDIC) in water. The in
      vitro assimilation model used was the brush border membrane vesicles (BBMV)
      system in which the BBMVs were incubated with CyDIC. Carotenoid suspensions in
      Tween were used as a reference. Regardless of the form in which the carotenoids
      were delivered to the BBMV preparation, a higher assimilation efficiency was
      observed for carotenes than for the xanthophyll lutein. At the highest donor
      solution concentration, supplying carotenoids in CyDIC produced a significant
      increase in carotenoid assimilation compared to the corresponding carotenoid
      suspensions in Tween. The assimilation process using CyDIC takes place by means
      of a dissociation process in which the carotenoids are released from the beta
      cyclodextrin to later be assimilated. At the highest concentration of CyDIC in
      the donor solution, the dissociation equilibrium will be shifted toward the free
      forms of the complex, thus increasing the amount of carotenoids available for
      assimilation. In another set of experiments, the effect of high-density
      lipoproteins as activity inhibitors for the receptors involved in carotenoid
      assimilation was analyzed. In carotenoid suspensions in Tween, with an inhibitor,
      a significant decrease in the assimilated quantity compared was observed with
      values reached without the inhibitor. Lutein presented the most significant
      decrease (70%). The fact that complete inhibition was not reached suggests that
      both simple and facilitated diffusion contributes to the assimilation process.
      When the donor solution composed of CyDIC and inhibitor was added, significant
      increases were observed in beta-carotene and lycopene assimilation for all
      concentrations and in lutein for the highest concentration. This effect is due to
      the exchange between lipoprotein lipid components and CyDIC, which promotes the
      dissociation and liberation processes of the carotenoid, which then becomes
      available for assimilation.

PMID- 20155914
TI  - Ultralow superharmonic resonance for functional nanowires.
AB  - Functional nanowires, made from materials such as zinc oxide, offer the promise
      of energy scavenging and precise sensing due to their vibrational properties, but
      their high intrinsic resonance frequencies (in the kilohertz to megahertz range)
      have limited the applications in nanotechnology. In this paper, we describe a
      method for introducing a new type of resonance at ultralow frequencies in ZnO
      nanowires. By using in situ ion implantation, nanodevice assembly, electronic
      signal generation, mechanical measurement, and electron beam characterization, we
      have achieved resonance at frequencies two orders of magnitude lower than the
      natural resonance frequency. Through both experimental investigation and
      theoretical simulation, we show that electric charge imbalance arising from
      focused ion beam exposure is responsible for the creation of this unprecedented
      superharmonic resonance behavior in ZnO nanowires.

PMID- 20155915
TI  - Leech-derived thrombin inhibitors: from structures to mechanisms to clinical
      applications.

PMID- 20155916
TI  - Structure-based design, synthesis, and biological studies of new anticancer
      norindenoisoquinoline topoisomerase I inhibitors.
AB  - On the basis of the superimposition of the crystal structures of
      norindenoisoquinoline 5 and topotecan (2) bound in the topoisomerase I-DNA
      covalent complex, as well as molecular docking and quantum chemical calculations,
      the substituted norindenoisoquinoline 14a was designed by transporting the 9
      dimethylaminomethyl group of topotecan to the 10-position of the
      norindenoisoquinoline 5. The desired compound 14a was synthesized and found to
      possess topoisomerase I inhibitory activity that was slightly better than that of
      the starting compound 5. A focused set of 10-substitued norindenoisoquinoline
      analogues were then synthesized. The imidazole-substituted compound 14c was
      highly cytotoxic when evaluated in a series of human leukemia, ovarian, and
      breast cancer cells.

PMID- 20155917
TI  - Synthesis and evaluation of a set of 4-phenylpiperidines and 4-phenylpiperazines
      as D2 receptor ligands and the discovery of the dopaminergic stabilizer 4-[3
      (methylsulfonyl)phenyl]-1-propylpiperidine (huntexil, pridopidine, ACR16).
AB  - Modification of the partial dopamine type 2 receptor (D(2)) agonist 3-(1
      benzylpiperidin-4-yl)phenol (9a) generated a series of novel functional D(2)
      antagonists with fast-off kinetic properties. A representative of this series,
      pridopidine (4-[3-(methylsulfonyl)phenyl]-1-propylpiperidine; ACR16, 12b), bound
      competitively with low affinity to D(2) in vitro, without displaying properties
      essential for interaction with D(2) in the inactive state, thereby allowing
      receptors to rapidly regain responsiveness. In vivo, neurochemical effects of 12b
      were similar to those of D(2) antagonists, and in a model of locomotor
      hyperactivity, 12b dose-dependently reduced activity. In contrast to classic D(2)
      antagonists, 12b increased spontaneous locomotor activity in partly habituated
      animals. The "agonist-like" kinetic profile of 12b, combined with its lack of
      intrinsic activity, induces a functional state-dependent D(2) antagonism that can
      vary with local, real-time dopamine concentration fluctuations around distinct
      receptor populations. These properties may contribute to its unique "dopaminergic
      stabilizer" characteristics, differentiating 12b from D(2) antagonists and
      partial D(2) agonists.

PMID- 20155918
TI  - Synthesis and biological evaluation of botulinum neurotoxin a protease
      inhibitors.
AB  - NSC 240898 was previously identified as a botulinum neurotoxin A light chain
      (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute
      Open Repository diversity set. Two types of analogues have been synthesized and
      shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an
      HPLC-based assay. These two series of compounds have also been evaluated for
      inhibition of anthrax lethal factor (LF), an unrelated metalloprotease, to
      examine enzyme specificity of the BoNT/A LC inhibition. The most potent inhibitor
      against BoNT/A LC in these two series is compound 12 (IC(50) = 2.5 microM, FRET
      assay), which is 4.4-fold more potent than the lead structure and 11.2-fold more
      selective for BoNT/A LC versus the anthrax LF metalloproteinase. Structure
      activity relationship studies have revealed structural features important to
      potency and enzyme specificity.

PMID- 20155919
TI  - Role of secondary sialic acid binding sites in influenza N1 neuraminidase.
AB  - Within influenza viral particles, the intricate balance between host cell binding
      and sialic acid receptor destruction is carefully maintained by the hemagglutinin
      (HA) and neuraminidase (NA) glycoproteins, respectively. A major outstanding
      question in influenza biology is the function of a secondary sialic acid binding
      site on the NA enzyme. Through a series of Brownian dynamics (BD) simulations of
      the avian N1, human pandemic N2, and currently circulating pandemic (H1)N1
      enzymes, we have probed the role of this secondary sialic acid binding site in
      the avian N1 subtype. Our results suggest that electrostatic interactions at the
      secondary and primary sites in avian NA may play a key role in the recognition
      process of the sialic acid receptors and catalytic efficiency of NA. This
      secondary site appears to facilitate the formation of complexes with the NA
      protein and the sialic acid receptors, as well as provide HA activity to a lesser
      extent. Moreover, this site is able to steer inhibitor binding as well, albeit
      with reduced capacity in N1, and may have potential implications for drug
      resistance or optimal inhibitor design. Although the secondary sialic acid
      binding site has previously been shown to be nonconserved in swine NA strains,
      our investigations of the currently circulating pandemic H1N1 strain of swine
      origin appears to have retained some of the key features of the secondary sialic
      acid binding site. Our results indicate possible lowered HA activity for this
      secondary sialic acid site, which may be an important event in the emergence of
      the current pandemic strain.

PMID- 20155920
TI  - Aryl-CF(3) bond-forming reductive elimination from palladium(IV).
AB  - This communication describes oxidatively induced Ar-CF(3) bond-forming reductive
      elimination from new Pd(II) complexes of general structure (L approximately
      L)Pd(II)(Ar)(CF(3)). The electrophilic fluorinating reagent N-fluoro-2,4,6
      trimethylpyridinium triflate promotes these reactions in good to excellent
      yields. The palladium(IV) intermediate ((t)Bu
      bpy)Pd(IV)(CF(3))(F)(OTf)(C(6)H(4)F) has been isolated, characterized, and
      demonstrated to undergo high yielding Ar-CF(3) coupling upon thermolysis. This
      work provides an attractive conceptual framework for the development of Pd(II/IV)
      catalyzed arene trifluoromethylation reactions.

PMID- 20155921
TI  - Pd nanoparticles embedded into a metal-organic framework: synthesis, structural
      characteristics, and hydrogen sorption properties.
AB  - The metal-organic framework MIL-100(Al) has been used as a host to synthesize Pd
      nanoparticles (around 2.0 nm) embedded within the pores of the MIL, showing one
      of the highest metal contents (10 wt %) without degradation of the porous host.
      Textural properties of MIL-100(Al) are strongly modified by Pd insertion, leading
      to significant changes in gas sorption properties. The loss of excess hydrogen
      storage at low temperature can be correlated with the decrease of the specific
      surface area and pore volume after Pd impregnation. At room temperature, the
      hydrogen uptake in the composite MIL-100(Al)/Pd is almost twice that of the
      pristine material. This can be only partially accounted by Pd hydride formation,
      and a "spillover" mechanism is expected to take place promoting the dissociation
      of molecular hydrogen at the surface of the metal nanoparticles and the diffusion
      of monatomic hydrogen into the porosity of the host metal-organic framework.

PMID- 20155922
TI  - Reversible photoswitchable fluorescence in thin films of inorganic nanoparticle
      and polyoxometalate assemblies.
AB  - A novel type of inorganic hybridized ultrathin film consisting of Preyssler-type
      polyoxometalates K(14)[Na(H(2)O)P(5)W(30)O(110)] (Na-POMs) and CdSe@CdS
      nanoparticles (NPs) was prepared on the solid substrates by a layer-by-layer
      assembly technique. The film exhibits reversible fluorescence switching behavior
      under control of irradiation with either UV light or visible light, which is
      ascribed to the selective occurrence of fluorescence resonance energy transfer
      between luminescent NPs and different states of photochromic Na-POMs.

PMID- 20155923
TI  - Solar driven water oxidation by a bioinspired manganese molecular catalyst.
AB  - A photoelectrochemical cell was designed that catalyzes the photooxidation of
      water using visible light as the sole energy source and a molecular catalyst,
      [Mn(4)O(4)L(6)](+) (1(+), L = bis(methoxyphenyl)phosphinate), synthesized from
      earth-abundant elements. The essential features include a photochemical charge
      separation system, [Ru(II)(bipy)(2)(bipy(COO)(2))], adhered to titania-coated FTO
      conductive glass, and 1(+) embedded within a proton-conducting membrane (Nafion).
      The complete photoanode represents a functional analogue of the water-oxidizing
      center of natural photosynthesis.

PMID- 20155924
TI  - Versatile phosphate phosphors ABPO(4) in white light-emitting diodes: collocated
      characteristic analysis and theoretical calculations.
AB  - The orthophosphate host family, A(I)B(II)PO(4) (A(I) = monovalent cation, B(II) =
      divalent cation), has recently been made available as phosphors that combine with
      near-UV lighting chips for use in solid-state white light-emitting diodes (LEDs).
      This study elucidates the crystalline structure and lattice parameters of the
      products via a solid-state reaction, using powder X-ray diffraction (XRD) and
      GSAS refinement. The versatility of the phosphor host A(I)B(II)PO(4) is
      established by examining isovalent substitutions of four cations in the structure
      Li or K for A(I), Sr or Ba for B(II)-and three doped activators, RE = Eu(2+),
      Tb(3+), and Sm(3+). The luminescence properties, decay time, and Commission
      Internationale de l'Eclairage (CIE) chromaticity index are determined for various
      concentrations of these activators and metal constituents of the host. The
      thermal stabilities of all of these compounds are determined for the first time
      from the crystal structure and the coordination environment of the rare-earth
      metal. The morphology, composition, and particle size were measured in detail.
      Finally, density functional calculations were performed using the generalized
      gradient approximation plus an on-site Coulombic interaction correction (GGA+U)
      scheme to investigate the electronic structures of the KSrPO(4) system. A concise
      model was proposed to explain the luminescence mechanism.

PMID- 20155925
TI  - Nanoparticle-based biocompatible and long-life marker for lysosome labeling and
      tracking.
AB  - In this paper, a novel biocompatible and long-life lysosome labeling and tracking
      method based on dye entrapped silica nanoparticles (DSiNPs) has been put forward.
      Through colocalization studies using LysoTracker Green as the standard lysosome
      marker, it has been demonstrated that DSiNPs selectively accumulated in lysosomes
      of Hela cells and the photostability of DSiNPs associated with lysosomes was
      detectable, at least, 30 times as long as that of LysoTracker Green involved in
      lysosomes. By comparison with LysoTracker Green and Alexa 488-dextran, the
      fluorescence of DSiNPs could be detected over a 5-day postrecultivation period
      and the staining pattern in lysosomes could be well retained after cell fixation
      and permeabilization. In addition, results from MTT assays showed that DSiNPs did
      not affect the viability of Hela cells at the concentration for lysosome
      labeling. Primary applications of DSiNPs were then further performed in lysosome
      tracking in chloroquine-treated Hela cells, and lysosome labeling of differnet
      cell lines, including MCF-7 cells, MEAR cells, and MSC cells. These results
      indicated that DSiNPs, therefore, can be used as a biocompatible, long-life, and
      highly photostable lysosome marker for lysosome-related studies.

PMID- 20155926
TI  - Monitoring real-time metabolism of living cells by fast two-dimensional NMR
      spectroscopy.
AB  - Living cell metabolism is often monitored by 1D NMR spectroscopy, but the
      spectral resolution and the short cell lifetime are certainly limiting aspects.
      2D spectroscopy does yield higher resolution but is time-consuming since
      acquisition of the second dimension requires several minutes. However, after only
      few minutes, oxygen starvation changes cell metabolism, and long acquisition
      times may yield spectra that do not represent the cell physiological state.
      Accordingly, metabolic studies of cells require fast NMR data acquisition. Here,
      we have applied band-selective optimized flip-angle short-transient (SOFAST)-HMQC
      techniques to (15)N-labeled cells, showing for the first time that it is possible
      to obtain 2D (1)H-(15)N correlation spectra of small metabolites directly in
      living cells, in a few seconds and with a high S/N ratio. SOFAST-HMQC spectra of
      (15)N-labeled Thalassiosira rotula diatoms cells can be acquired in 10-15 s, and,
      as an application, we have detected a progressive variation of the amino acid
      content when diatoms are exposed to UV-B radiation, with no need of long
      analytical procedures to quantify the metabolic changes. We believe that fast
      acquisition techniques can easily be extended to other cell systems, foreseeing a
      wide application in the emerging fields of metabolomics and metabonomics, being
      able to picture the "instantaneous" in-cell metabolism.

PMID- 20155927
TI  - Spinel to CaFe2O4 transformation: mechanism and properties of beta-CdCr2O4.
AB  - The CdCr(2)O(4) spinel transforms to a 10.6% denser new polymorph of the
      CaFe(2)O(4)-type structure at 10 GPa and 1100 degrees C. This new polymorph has a
      honeycomb-like structure because of double rutile-type chains formed by [Cr-O(6)]
      edge-shared octehedra. This crystal structure is prone to be magnetically
      frustrated and presents low-dimensional antiferromagnetism at 25 K < T < 150 K,
      accompanied by more complex interactions as the temperature decreases. These
      transitions are evidenced by magnetic susceptibility and heat capacity
      measurements. We also discuss a possible structural mechanism for the
      transformation.

PMID- 20155928
TI  - An alkali-metal ion extracted layered compound as a template for a metastable
      phase synthesis in a low-temperature solid-state reaction: preparation of
      brookite from K0.8Ti1.73Li0.27O4.
AB  - We have designed a new approach to synthesize brookite, i.e., to extract alkali
      metal ions from K(0.8)Ti(1.73)Li(0.27)O(4) (KTLO) and to apply simultaneous heat
      treatment to the remaining lepidocrocite-type layers of TiO(6) octahedra. For the
      alkali-metal ion extraction and the simultaneous heat treatment, KTLO was heated
      at 400 degrees C with polytetrafluoroethylene (PTFE) in flowing Ar. PTFE has been
      found to be an effective agent to extract strongly electropositive alkali-metal
      ions from KTLO because of the strong electronegativity of F as its component. The
      product of this reaction consists of a mixture of brookite, K(2)CO(3), LiF, and
      PTFE derivatives, indicating the complete extraction of K(+) and Li(+) from KTLO
      and formation of brookite from the lepidocrocite-type layer of TiO(6) octahedra
      as a template. This brookite has a partial replacement of O(2-) with F(-) and/or
      slight oxygen deficiency; thus, its color is light-bluish gray. Fully oxidized
      brookite formation and complete decomposition of PTFE derivatives have been
      achieved by further heating in flowing air, and coproduced alkali-metal salts
      have been removed by washing in water. Powder X-ray diffraction, Raman
      spectroscopy, and chemical analysis results have confirmed that the final
      brookite product treated at 600 degrees C is single phase, and it is white. The
      method to extract alkali-metal ions from a crystalline material using PTFE is
      drastically different from the common methods such as soft-chemical and
      electrochemical reactions. It is likely that this new synthetic approach is
      applicable to other layered systems to prepare a diverse family of compounds,
      including novel metastable ones.

PMID- 20155929
TI  - Discovery of natural perchlorate in the Antarctic Dry Valleys and its global
      implications.
AB  - In the past few years, it has become increasingly apparent that perchlorate
      (ClO(4)(-)) is present on all continents, except the polar regions where it had
      not yet been assessed, and that it may have a significant natural source. Here,
      we report on the discovery of perchlorate in soil and ice from several Antarctic
      Dry Valleys (ADVs) where concentrations reach up to 1100 microg/kg. In the driest
      ADV, perchlorate correlates with atmospherically deposited nitrate. Far from
      anthropogenic activity, ADV perchlorate provides unambiguous evidence that
      natural perchlorate is ubiquitous on Earth. The discovery has significant
      implications for the origin of perchlorate, its global biogeochemical
      interactions, and possible interactions with the polar ice sheets. The results
      support the hypotheses that perchlorate is produced globally and continuously in
      the Earth's atmosphere, that it typically accumulates in hyperarid areas, and
      that it does not build up in oceans or other wet environments most likely because
      of microbial reduction on a global scale.

PMID- 20155930
TI  - Synthesis of a novel Sn(IV) porphycene-ferrocene triad linked by axial
      coordination and solvent polarity effect in photoinduced charge separation
      process.
AB  - A novel Sn(IV) porphycene-ferrocene triad molecule, trans
      bis(ferrocenecarboxylato)(2,3,6,7,12,13,16,17-octaethylporphycenato)tin(IV),
      [Sn(IV)(OEPc)(FcCOO)(2)] (2), was synthesized and fully characterized by various
      spectroscopic methods. This is the first example of a metalloporphycene triad
      linked by the axial coordination of two functionalized units to a metallocenter.
      The steady-state fluorescence measurement indicated the efficient fluorescence
      quenching by coordination of the ferrocenecarboxylic acid in comparison to the
      corresponding dihydroxy-Sn(IV) porphycene, [Sn(IV)(OEPc)(OH)(2)] (1) (1, Phi(F) =
      0.094; 2, Phi(F) = 0.01). The electron transfer process from the ferrocene units
      to the excited Sn(IV) porphycene was directly observed by subpicosecond transient
      absorption spectroscopy in acetonitrile (polar solvent) and toluene (nonpolar
      solvent). In acetonitrile, the transient species attributed to the Sn(IV)
      porphycene radical anion was observed at 750 and 850 nm within 1 ps after the
      excitation, and then the generated charge separation state disappeared with a
      value of 6.9 x 10(11) s(-1) for the time constant. On the other hand, the
      generated charge separation state decayed with two components, 3.9 x 10(11) and
      9.6 x 10(9) s(-1) time constants, in toluene. For the observed two-component
      decay in toluene, a significant equilibrium between the charge separation state
      and the triplet state was proposed because these energy levels are close to each
      other. Therefore, the solvent-polarity-dependent long-lived charge separation
      state was obtained in the Sn(IV) porphycene-ferrocene triad system. The electron
      transfer upon excitation of the Sn(IV) porphyrin of [Sn(IV)(OEP)(FcCOO)(2)] (4),
      in which OEP denotes the 2,3,6,7,12,13,16,17-octaethylporphyrin ligand, was
      observed. However, no equilibrium between the charge separation and the triplet
      states was observed in both the acetonitrile and toluene. The difference in the
      charge recombination processes of the Sn(IV)-porphycene and -porphyrin is due to
      the small HOMO-LUMO gap and the large driving force (-DeltaG(CS)) of 2 compared
      to that of 4, which resulted in the energy level of the charge separation state
      close to the triplet state in toluene. Furthermore, the large driving force (
      DeltaG(CS)) of 2 compared to that of 4 is attributed to the significant
      stabilization of the LUMO energy level caused by a decrease in the molecular
      symmetry and a large porphycene pi-electron framework. This result indicates that
      porphycenes are excellent candidates as an electron acceptor in photoinduced
      electron transfer systems.

PMID- 20155931
TI  - Design and synthesis of cationic drug carriers based on hyperbranched poly(amine
      ester)s.
AB  - Novel cationic drug carriers based on hyperbranched poly(amine-ester)s were
      successfully prepared through proton-transfer polymerization. Both vinyl and
      epoxy groups of commercially available glycidyl methacrylate monomer could be
      polymerized through oxyanionic initiation of triethanolamine in the presence of
      potassium hydride catalysis. By changing the molar ratios of
      triethanolamine/glycidyl methacrylate or potassium hydride/triethanolamine, we
      obtained a series of hyperbranched poly(amine-ester)s. The generation of highly
      branched poly(amine-ester)s was confirmed by (13)C DEPT-135 NMR and 2D NMR
      techniques, and their degrees of branching were found to be 0.47 to 0.68. The
      structure and properties of hyperbranched poly(amine-ester)s were analyzed by
      dynamic light scattering, gel permeation chromatography, Fourier transformed
      infrared, differential scanning calorimeter, and zeta-potential measurements.
      Methyl tetrazolium (MTT) assay suggested that the cell viability after 48 h
      incubation with hyperbranched poly(amine-ester) concentrations up to 1 mg/mL
      remained nearly 100% compared with the untreated cells. The high cellular uptake
      of these cationic polymers was confirmed by flow cytometry and confocal laser
      scanning microscopy. Furthermore, conjugation of a model hydrophobic anticancer
      drug chlorambucil to hyperbranched poly(amine-ester)s inhibited the proliferation
      of MCF-7 breast cancer cells. MTT assay indicated that the chlorambucil dose
      required for 50% cellular growth inhibition against MCF-7 cells was 120
      microg/mL. All of these results show that hyperbranched poly(amine-ester)s are
      promising materials for drug delivery.

PMID- 20155932
TI  - Eremophilane-type sesquiterpenes from the fungus Xylaria sp. BCC 21097.
AB  - Seven new eremophilane-type sesquiterpenoids (1-5, 7, and 8) and the known
      mairetolide F (6) were isolated from the endophytic Xylaria sp. BCC 21097. A new
      furofurandione (9) was also isolated from the fungal extract. The structures of
      the new compounds were elucidated by analyses of NMR spectroscopic and mass
      spectrometry data in combination with chemical reaction studies.
      Eremophilanolides possessing an alpha-methylene-gamma-lactone (1-3) exhibited
      moderate cytotoxic activities, while related analogues bearing an endo double
      bond (6 and 7) were inactive.

PMID- 20155933
TI  - Detection of novel functional selectivity at M3 muscarinic acetylcholine
      receptors using a Saccharomyces cerevisiae platform.
AB  - "Functional selectivity", although new to many chemists and biologists only a few
      years ago, has now become a dominant theme in drug discovery. This concept posits
      that different ligands engender unique receptor conformations such that only a
      subset of signaling pathways linked to a given receptor are recruited. However,
      successful exploitation of the phenomenon to achieve pathway-based selectivity
      requires the ability to routinely detect it when assessing ligand behavior. We
      have utilized different strains of the yeast S. cerevisiae, each expressing a
      specific human Galpha/yeast Gpa1 protein chimera coupled to a MAP kinase-linked
      reporter gene readout, to investigate the signaling of the M(3) muscarinic
      receptor, a G protein-coupled receptor (GPCR) for which various antagonists are
      used clinically. Using this novel platform, we found that the "antagonists",
      atropine, N-methylscopolamine, and pirenzepine, were inverse agonists for
      Gpa1/Galpha(q) but low efficacy agonists for Gpa1/Galpha(12.) Subsequent studies
      with atropine performed in mammalian 3T3 cells validated these findings by
      demonstrating inverse agonism for G(q/11)-mediated calcium mobilization but
      positive agonism for G(12)-mediated membrane ruffling. This is the first study to
      utilize a yeast platform to discover pathway-biased functional selectivity in a
      GPCR. In addition to the likely applicability of this approach for identifying
      biased signaling by novel chemical entities, our findings also suggest that
      currently marketed medications may exhibit hitherto unappreciated functional
      selectivity.

PMID- 20155934
TI  - Application of polyhydroxyalkanoate granules for sizing of paper.
AB  - Polyhydroxyalkanoates (PHAs) are characterized by the chemistry of the
      biodegradable inclusions inside the microbial membrane. They are produced by a
      wide variety of bacteria, where they function as energy and carbon storage
      materials. This intracellular Bioplastic forms a stable latex suitable for
      surface treatments of paper such as sizing and coating. In this work, we compare
      native granules and artificial granules made from market poly(3-hydroxybutyrate)
      (PHB) and poly(3-hydroxybutyrate-co-hydroxyvalerate), P(3HB-co-3HV), for their
      ability as sizing agent. Paper sizing was assayed by measuring the resistance of
      sized paper to penetration by aqueous fluids. Our results indicate that the
      sizing effect of PHAs is dependent on several factors, such as, paper drying
      temperature, drying time, pressure, and polymer composition, that is,
      homopolymer, random copolymer, and texture of granules. The sizing efficiency of
      the copolymer is generally poor compared to the PHB homopolymer. In addition to
      water permeability, the tensile strength of sized paper was measured and physical
      properties of granule suspensions were recorded using SEM microscopy, X-ray
      diffraction, and dynamic light scattering.

PMID- 20155935
TI  - Sorption of proteins onto porous single-component poly(vinyl amine) multilayer
      thin films.
AB  - Porous multilayer thin films consisting solely of cross-linked poly(vinyl amine)
      ((PVAm)(n)) were generated by a selective cross-linking of the PVAm layers in the
      [PVAm/poly(acrylic acid) (PAA)](n) thin films, followed by the removal of PAA. A
      regular increase in the (PVAm/PAA)(n) multilayer onto silica particles was
      observed by potentiometric titration when PVAm with a low molar mass (M(w) = 15
      000 g mol(-1)) was used in the construction of LbL thin films. The amount of
      human serum albumin (HSA) loaded on the single-component (PVAm)(5) thin film was
      approximately 32 mg HSA/g of hybrid when PVAm with a molar mass of 15 000 g mol(
      1) was used compared with the single-component film prepared with PVAm with a
      molar mass of 340 000 g mol(-1) when the amount of HSA loaded was 15.5 mg HSA/g
      of hybrid. The sorption modalities of HSA and bovine serum albumin (BSA) onto the
      single-component thin films deposited on silicon wafers as a function of the
      number of PVAm layers was investigated by atomic force microscopy and contact
      angle measurements. The decrease in the film roughness and the increase in the
      film wettability after the loading of both proteins showed the protein was mainly
      absorbed into the porous (PVAm)(n) thin film.

PMID- 20155936
TI  - Region-specific protein abundance changes in the brain of MPTP-induced
      Parkinson's disease mouse model.
AB  - Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in
      the nigrostriatal region of the brain; however, the neurodegeneration extends
      well beyond dopaminergic neurons. To gain a better understanding of the molecular
      changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively
      analyze the proteome changes in four brain regions (striatum, cerebellum, cortex,
      and the rest of brain) using a MPTP-induced PD mouse model with the objective to
      identify potential nigrostriatal-specific and other region-specific protein
      abundance changes. The combined analyses resulted in the identification of 4,895
      nonredundant proteins with at least two unique peptides per protein. The relative
      abundance changes in each analyzed brain region were estimated based on the
      spectral count information. A total of 518 proteins were observed with
      substantial MPTP-induced abundance changes across different brain regions. A
      total of 270 of these proteins were observed with specific changes occurring
      either only in the striatum and/or in the rest of the brain region that contains
      substantia nigra, suggesting that these proteins are associated with the
      underlying nigrostriatal pathways. Many of the proteins that exhibit changes were
      associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin
      system, calcium signaling, the oxidative stress response, and apoptosis. A set of
      proteins with either consistent change across all brain regions or with changes
      specific to the cortex and cerebellum regions were also detected. Ubiquitin
      specific protease (USP9X), a deubiquination enzyme involved in the protection of
      proteins from degradation and promotion of the TGF-beta pathway, exhibited
      altered abundance in all brain regions. Western blot validation showed similar
      spatial changes, suggesting that USP9X is potentially associated with
      neurodegeneration. Together, this study for the first time presents an overall
      picture of proteome changes underlying both nigrostriatal pathways and other
      brain regions potentially involved in MPTP-induced neurodegeneration. The
      observed molecular changes provide a valuable reference resource for future
      hypothesis-driven functional studies of PD.

PMID- 20155938
TI  - Macrocyclization of linear peptides enabled by amphoteric molecules.
AB  - There has been enormous interest in both naturally occurring and synthetic cyclic
      peptides as scaffolds that preorganize a given amino acid sequence into a rigid
      conformation. Such molecules have been employed as nanomaterials, imaging agents,
      and therapeutics. Unfortunately, the laboratory synthesis of cyclic peptides
      directly from linear precursors is afflicted by several thermodynamic and kinetic
      challenges, resulting in low chemical yields and poor chemo- and
      stereoselectivities. Here we report that amphoteric amino aldehydes can be used
      for efficient syntheses of cyclic peptides in high yields and selectivities
      starting from alpha-amino acids or linear peptides. The cyclizations effectively
      operate at unusually high molar concentrations (0.2 M), while side processes such
      as epimerization and cyclodimerization are not observed. The products are
      equipped with sites that allow for a highly specific, late-stage structural
      modification. The overall efficiency of the macrocyclization is due to the
      coexistence of nucleophilic and electrophilic reaction centers in amphoteric
      amino aldehydes.

PMID- 20155937
TI  - Potential for misidentification of environmentally persistent free radicals as
      molecular pollutants in particulate matter.
AB  - Environmentally persistent free radicals (EPFRs) have been shown to form on the
      surfaces of various types of transition metal-containing particulate matter (PM),
      and it has been demonstrated they are capable of initiating adverse health
      impacts. Following sonification and solvent extraction for chemical analysis,
      they are partially converted to molecular species. Alcoholic solvents extracted
      the EPFRs with near 100% efficiency, while nonpolar hydrocarbon solvents
      exhibited <20% efficiency and dichloromethane exhibited 20-55% efficiency. The
      extracted radicals reacted in solution to form multiple molecular reaction
      products including catechol, hydroquinone, phenol, chlorinated phenols, dibenzo-p
      dioxin, and dibenzofuran. This suggests that EPFRs in environmental samples are
      indistinguishable from molecular pollutants and are subject to misidentification
      as molecular adsorbates when traditional extraction and chemical analysis methods
      are employed. On the basis of these findings, the origin of the toxicity of
      particulate matter contaminated with toxic organic compounds should be considered
      for re-evaluation to include the possibility that EPFRs may be a significant
      contributor, and the impact of some molecular pollutants may have been
      overestimated.

PMID- 20155939
TI  - Three-level topology switching in a molecular Mobius band.
AB  - Mobius pi-conjugation in cyclic molecules leads to the reversal of Huckel
      aromaticity rules and affects the electronic and magnetic properties of these
      systems. We found the first example of a medium-sized macrocyclic structure that
      is sufficiently flexible to switch between three distinct pi-conjugation
      topologies, planar (T0), Mobius (T1), and twisted Huckel (T2), without changing
      its oxidation level. The switching is under thermodynamic and kinetic control and
      can be realized in a three- or four-step cycle. On titration with trifluoroacetic
      acid (TFAH) or dichloroacetic acid (DCAH), the Mobius free base (T1-H(2)), which
      is the preferred structure in dichlorofluoromethane at 150 K, undergoes a series
      of acid-base reactions involving changes of the pi-conjugation topology. The
      forms observed in the course of titration involve a Mobius aromatic monocation
      ([T1-H(3)](+)), an antiaromatic twisted Huckel species ([T2-H(4)(A)](+))
      containing a coordinated carboxylate anion (A = TFA, DCA), and two additional
      Mobius forms ([T1-H(4)(A)(HA)(n)](+) (n = 1, 2)), containing complex carboxylate
      anions. The protonated forms undergo a thermally activated ring planarization to
      yield an antiaromatic quasi-planar dication [T0-H(4)](2+), characterized in the
      solid state as a TFA salt. The corresponding free base (T0-H(2)) is metastable
      but can be trapped by addition of triethylamine at low temperatures.

PMID- 20155940
TI  - Localization of flavonoids in seeds by cluster time-of-flight secondary ion mass
      spectrometry imaging.
AB  - Time-of-flight secondary ion mass spectrometry imaging has been used to map
      flavonoids in fresh seed sections of peas (Pisum sativum) and Arabidopsis
      thaliana. While for peas a very simple preparation method derived from mammalian
      tissue imaging could be utilized, several preparation methods had to be tested
      for the A. thaliana seeds before obtaining tissue sections on which the
      diagnostic ions were not delocalized. For such small and stiff biological
      material, none of the methods currently used in histology or scanning electron
      microscopy could be transferred to mass spectrometry imaging. Only the embedding
      of the fresh seeds in a polyester resin, followed by the analysis of the block
      after having obtained a flat surface section with a diamond blade, gave sensitive
      and reproducible results. Several flavonoid ions have been detected in the
      sections, showing increased concentrations of flavonoids in the seed coats. The
      method was finally applied to confirm the variations in the flavonoid content of
      seeds from different A. thaliana mutants.

PMID- 20155941
TI  - Investigations of low-frequency vibrational dynamics and ligand binding kinetics
      of cystathionine beta-synthase.
AB  - Vibrational coherence spectroscopy is used to study the low frequency dynamics of
      the truncated dimer of human cystathionine beta-synthase (CBS). CBS is a
      pyridoxal-5'-phosphate-dependent heme enzyme with cysteine and histidine axial
      ligands that catalyzes the condensation of serine and homocysteine to form
      cystathionine. A strong correlation between the "detuned" coherence spectrum
      (which probes higher frequencies) and the Raman spectrum is demonstrated, and a
      rich pattern of modes below 200 cm(-1) is revealed. Normal coordinate structural
      decomposition (NSD) of the ferric CBS crystal structure predicts the enhancement
      of normal modes with significant heme "doming", "ruffling", and "saddling"
      content, and they are observed in the coherence spectra near approximately 40,
      approximately 60, and approximately 90 cm(-1). When pH is varied, the relative
      intensities and frequencies of the low frequency heme modes indicate the presence
      of a unique protein-induced heme structural perturbation near pH 7 that differs
      from what is observed at higher or lower pH. For ferric CBS, we observe a new
      mode near approximately 25 cm(-1), possibly involving the response of the
      protein, which exhibits a phase jump of approximately pi for excitation on the
      blue and red side of the Soret band maximum. The low frequency vibrational
      coherence spectrum of ferrous CBS is also presented, along with our efforts to
      probe its NO-bound complex. The CO geminate rebinding kinetics of CBS are similar
      to the CO-bound form of the gene activator protein CooA, but with the appearance
      of a significant additional kinetic inhomogeneity. Analysis of this inhomogeneity
      suggests that it arises from the two subunits of CBS and leads to a factor of
      approximately 20 for the ratio of the average CO geminate rebinding rates of the
      two subunits.

PMID- 20155942
TI  - ZnO particulate matter requires cell contact for toxicity in human colon cancer
      cells.
AB  - There is ongoing concern regarding the toxicity of nanoparticles with sizes less
      than 100 nm as compared to larger particles of the same nominal substance. Two
      commercial ZnO types, one sold as a 8-10 nm powder and the other described as 
      325 mesh (<44 mum) powder, were evaluated in human colon-derived RKO cells. The
      powders had a volume-to-surface area ratio equivalent to 40 and 330 nm spheres,
      respectively. Both materials formed micrometer-sized agglomerates in cell culture
      media. The nanosized ZnO was more cytotoxic than the micrometer-sized ZnO with
      LC(50) values of 15 +/- 1 and 29 +/- 4 mug/cm(2), respectively. Transfer of Zn
      from the solid phase to the cell culture media in the presence of RKO cells was
      time- and concentration-dependent. However, direct particle-cell contact was
      required for RKO cell cytotoxicity, and the toxicity of particles was independent
      of the amount of soluble Zn in the cell culture media. The mechanism of cell
      death includes the disruption of mitochondrial function. Robust markers of
      apoptosis, Annexin V staining, loss of mitochondrial potential, and increased
      generation of superoxide were observed when cells were treated with ZnO
      particulate matter but not when treated with comparable concentration of a
      soluble Zn salt. Both ZnO samples induced similar mechanisms of toxicity, but
      there was a statistically significant increase in potency per unit mass with the
      smaller particles.

PMID- 20155943
TI  - Electrochemical aptameric recognition system for a sensitive protein assay based
      on specific target binding-induced rolling circle amplification.
AB  - A reusable aptameric recognition system was described for the electrochemical
      detection of the protein PDGF-BB based on the target binding-induced rolling
      circle amplification (RCA). A complementary DNA (CDNA), linear padlock probe, and
      primer probe were utilized to introduce a RCA process into the aptamer-target
      binding event while a new aptamer was elegantly designed via lengthening the
      original aptamer by the complement to the CDNA. The aptameric sensing system
      facilitates the integration of multiple functional elements into a signaling
      scheme: a unique electrochemical technique, an attractive RCA process, reversible
      DNA hybridization, and desirable aptameric target recognition. This RCA-based
      electrochemical recognition system not only exhibits excellent performance (e.g.,
      a detection limit of 6.3 x 10(-11) M, a linear dynamic range of 2 orders of
      magnitude, high specificity, and satisfactory repeatability) but also overcomes
      the limitations associated with conventional aptameric biosensors (e.g.,
      dependence of signaling target binding on specific aptamer sequence or
      requirement of sandwich assays for two or more binding sites per target
      molecule). A recovery test demonstrated the feasibility of the developed target
      protein assay. Given the attractive characteristics, this aptameric recognition
      platform is expected to be a candidate for the detection of proteins and other
      ligands of interest in both fundamental and applied research.

PMID- 20155944
TI  - Noncovalent functionalization of BN nanotubes with perylene derivative molecules:
      an ab initio study.
AB  - The noncovalent functionalization of boron nitride nanotubes (BNNTs) with
      perylene-derived molecules has been reported experimentally [Wang et al. J. Am.
      Chem. Soc. 2008, 130, 8144]. Here we study the structural and electronic
      properties for the perylene-derivative functionalized BNNTs using first
      principles calculations. Our calculations highlight the electronic structure
      modifications of BNNT through the noncovalent functionalization and demonstrate
      that van der Waals interactions between the adsorbed perylene derivatives and
      host BN layers facilitate the functionalization. We also provide an explanation
      for the red-shift of optical adsorption bands observed in experiment and discuss
      improvements in theoretical calculations of noncovalently functionalized BNNTs.

PMID- 20155945
TI  - Biotransformation of plant secondary metabolite decursin by Mycobacterium sp.
      PYR1001.
AB  - Decursin and its structural isomer decursinol angelate are major secondary
      metabolites in the root of Angelica gigas Nakai which possess several
      chemotherapeutic properties. We isolated bacteria capable of transforming
      decursin and determined metabolites and biotransformation kinetics. Decursinol
      angelate was not metabolized to any significant extent. Resting cells of
      Mycobacterium sp. PYR1001 were able to transform decursin. After 24 h incubation,
      5 mM of decursin was completely transformed to a metabolite, the structure of
      which was determined by NMR and mass spectral analyses to be decursinol. This
      conversion was shown to be catalyzed by an esterase activity, and the activity
      was found to be specific for decursin. These results suggest that strain PYR1001
      can be successfully used to transform decursin for the production of decursinol,
      a compound known to have cancer chemopreventive activity.

PMID- 20155946
TI  - Photochemical decomposition of N2O by Lyman-alpha radiation: scientific basis for
      a chemical actinometer.
AB  - A novel IR method for measuring the kinetics of N(2)O photodecomposition has been
      devised and used to calibrate the flux of Lyman-alpha (10.2 eV) radiation from a
      H(2)/Ar microwave discharge lamp. The photodecomposition of N(2)O occurs with a
      weak pressure dependence due to the operation of a wall effect consuming some
      photogenerated active oxygen species. This effect is removed by working at high
      N(2)O pressures. The Lyman-alpha flux from the lamp is 1.28 +/- 0.36 x 10(15)
      photons cm(-2) s(-1).

PMID- 20155947
TI  - Layer-by-layer incorporation of growth factors in decellularized aortic heart
      valve leaflets.
AB  - Aortic heart valve disease is a growing health problem and a tissue-engineered
      aortic heart valve could be a promising therapy. In this paper, decellularized
      porcine aortic heart valve leaflets are used as scaffolds and loaded with growth
      factor and heparin via layer-by-layer electrostatic deposition (LbL technique)
      with the final purpose to stimulate and control cellular processes. Binding and
      subsequent release of heparin and basic fibroblast growth factor (bFGF) from
      aortic valve leaflets were assessed qualitatively by immunohistochemistry and
      quantitatively by radioactive labeling methods. It was observed that the amount
      of heparin and bFGF bound to aortic heart valve leaflets was directly
      proportional to the concentration of heparin and bFGF in the incubation medium.
      Release of heparin and bFGF from the decellularized heart valve leaflets at
      physiological conditions was sustained over 4 days while preserving the
      biological activity of the released growth factor.

PMID- 20155948
TI  - Chitosan-coated octadecyl-functionalized magnetite nanoparticles: preparation and
      application in extraction of trace pollutants from environmental water samples.
AB  - In the present study, chitosan-coated octadecyl-functionalized magnetite
      nanoparticles (Fe(3)O(4)-C(18)-chitosan MNPs) are synthesized and used as an
      adsorbent to extract trace analytes from environmental water samples. The
      magnetic nanoparticles, 20 nm in diameter, are of uniform size and have a high
      magnetic saturation value of 52 emu g(-1), which endue the adsorbent with a large
      surface area and convenience of isolation. The anionic pollutants, perfluorinated
      compounds (PFCs), are trapped by the octadecyl group of the interior hydrophobic
      layer. The positively charged chitosan polymer coating also contributes to PFC
      enrichment. At the same time, the coating improves the dispersibility of MNPs in
      aqueous solution and enhances the anti-interference ability of the adsorbent to
      natural organic macromolecules in complex samples by size exclusion or
      electrostatic repulsion. A liquid chromatography-tandem mass spectrometry system
      is employed in the determination of PFCs after preconcentration with the MNP
      adsorbent. The predominant factors affecting preconcentration are investigated
      and optimized. Under the selected conditions, concentration factors of 1000 are
      achieved by extracting the analytes from 500 mL of several environmental water
      samples and concentrating the eluants to 0.5 mL with a nitrogen flow. The method
      detection limits obtained for perfluorooctanoic acid (PFOA),
      perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA),
      perluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA),
      perfluorododecanoic acid (PFDoDA), and perfluorotetradecanoic acid (PFTA) in
      Gaobeidian wastewater are 0.24, 0.093, 0.24, 0.14, 0.075, 0.24, and 0.17 ng L(
      1), respectively. Recoveries of PFOA, PFOS, PFNA, PFDA, PFUnDA, PFDoDA, and PFTA
      are in the ranges of 88-108%, 63-112%, 79-109%, 56-107%, 66-106%, 56-106%, and 66
      103% for four spiked water samples with low relative standard deviation (2-8%),
      which indicates good method precision. The advantages of this novel adsorbent are
      high extraction efficiency, anti-interference, and convenient operation.

PMID- 20155949
TI  - Miniaturized planar chromatography using office peripherals.
AB  - High-performance thin-layer chromatography is a separation technique commonly
      used to identify and quantify components in chemical mixtures. Sophisticated
      analytical tools are required to extract the full analytical power from this
      technique and especially for miniaturized planar chromatography its utility has
      not been harnessed. A new approach uses an elegant, simplified system assembled
      from ordinary consumer printers and scanners to perform separations on monolithic
      and nanostructured ultrathin-layer phases. This system is shown to outperform
      existing planar chromatographic tools for analysis on miniaturized plates.
      Analysis can be completed in a manner of minutes, running numerous samples in
      parallel at a reduced cost, with very low sample and reagent volumes, all using a
      familiar computer interface with common office peripherals.

PMID- 20155950
TI  - Kinetic and structural analysis of substrate specificity in two copper amine
      oxidases from Hansenula polymorpha.
AB  - The structural underpinnings of enzyme substrate specificity are investigated in
      a pair of copper amine oxidases (CAOs) from Hansenula polymorpha (HPAO-1 and HPAO
      2). The X-ray crystal structure (to 2.0 A resolution) and steady state kinetic
      data of the second copper amine oxidase (HPAO-2) are presented for comparison to
      those of HPAO-1. Despite 34% sequence identity and superimposable active site
      residues implicated in catalysis, the enzymes vary considerably in their
      substrate entry channel. The previously studied CAO, HPAO-1, has a narrow
      substrate channel. In contrast, HPAO-2 has a wide funnel-shaped substrate
      channel, which also contains a side chamber. In addition, there are a number of
      amino acid changes within the channels of HPAO-2 and HPAO-1 that may sterically
      impact the ability of substrates to form covalent Schiff base catalytic
      intermediates and to initiate chemistry. These differences can partially explain
      the greatly different substrate specificities as characterized by k(cat)/K(m)
      value differences. In HPAO-1, the k(cat)/K(m) for methylamine is 330-fold greater
      than for benzylamine, whereas in HPAO-2, it is benzylamine that is the better
      substrate by 750-fold. In HPAO-2, an inflated (D)k(cat)/K(m)(methylamine) in
      relation to (D)k(cat)/K(m)(benzylamine) indicates that proton abstraction has
      been impeded more than substrate release. In HPAO-1, (D)k(cat)/K(m)(S) changes
      little with the slow substrate and indicates a similar increase in the energy
      barriers that control both substrate binding and subsequent catalysis. In neither
      case is k(cat)/K(m) for the second substrate, O(2), significantly altered. These
      results reinforce the modular nature of the active sites of CAOs and show that
      multiple factors contribute to substrate specificity and catalytic efficiency. In
      HPAO-1, the enzyme with the smaller substrate binding pocket, both initial
      substrate binding and proton loss are affected by an increase in substrate size,
      while in HPAO-2, the enzyme with the larger substrate binding pocket, the rate of
      proton loss is differentially affected when a phenyl substituent in the substrate
      is reduced to the size of a methyl group.

PMID- 20155951
TI  - Bovine chymosin: a computational study of recognition and binding of bovine kappa
      casein.
AB  - Bovine chymosin is an aspartic protease that selectively cleaves the milk protein
      kappa-casein. The enzyme is widely used to promote milk clotting in cheese
      manufacturing. We have developed models of residues 97-112 of bovine kappa-casein
      complexed with bovine chymosin, using ligand docking, conformational search
      algorithms, and molecular dynamics simulations. In agreement with limited
      experimental evidence, the model suggests that the substrate binds in an extended
      conformation with charged residues on either side of the scissile bond playing an
      important role in stabilizing the binding pose. Lys111 and Lys112 are observed to
      bind to the N-terminal domain of chymosin displacing a conserved water molecule.
      A cluster of histidine and proline residues (His98-Pro99-His100-Pro101-His102) in
      kappa-casein binds to the C-terminal domain of the protein, where a neighboring
      conserved arginine residue (Arg97) is found to be important for stabilizing the
      binding pose. The catalytic site (including the catalytic water molecule) is
      stable in the starting conformation of the previously proposed general acid/base
      catalytic mechanism for 18 ns of molecular dynamics simulations.

PMID- 20155952
TI  - Relationships among visual cycle retinoids, rhodopsin phosphorylation, and
      phototransduction in mouse eyes during light and dark adaptation.
AB  - Phosphorylation and regeneration of rhodopsin, the prototypical G-protein-coupled
      receptor, each can influence light and dark adaptation. To evaluate their
      relative contributions, we quantified rhodopsin, retinoids, phosphorylation, and
      photosensitivity in mice during a 90 min illumination followed by dark
      adaptation. During illumination, all-trans-retinyl esters and, to a lesser
      extent, all-trans-retinal accumulate and reach the steady state in <1 h. Each
      major phosphorylation site on rhodopsin reaches a steady state level of
      phosphorylation at a different time during illumination. The dominant factor that
      limits dark adaptation is isomerization of retinal. During dark adaptation,
      dephosphorylation of rhodopsin occurs in two phases. The faster phase corresponds
      to rapid dephosphorylation of regenerated rhodopsin present at the end of the
      illumination period. The slower phase corresponds to dephosphorylation of
      rhodopsin as it forms by regeneration. We conclude that rhodopsin phosphorylation
      has three physiological functions: it quenches phototransduction, reduces
      sensitivity during light adaptation, and suppresses bleached rhodopsin activity
      during dark adaptation.

PMID- 20155953
TI  - Preparation of enantiopure substituted piperidines containing 2-alkene or 2
      alkyne chains: application to total syntheses of natural quinolizidine-alkaloids.
AB  - A general method for the preparation of enantiopure 2-alkene- or 2-alkyne
      containing chain substituted piperidines was established by using nonracemic
      Betti base as a chiral auxiliary. The key step is that the auxiliary residue was
      removed by a novel base-catalyzed N-debenzylation via a formation of o-quinone
      methide mechanism in stead of the traditional hydrogenolysis, by which the alkene
      or alkyne groups survived. By this method, ten 2-alkene- or 2-alkyne-containing
      chain substituted piperidines were prepared on the gram scale within a few hours.
      To demonstrate the efficiency of the method and the versatility of the product,
      total syntheses of natural alkaloids (+)-pelletierine, (-)-lasubine II, and (+)
      cermizine C were achieved by using (S)-2-allyl-N-Boc-piperidine as a versatile
      building block.

PMID- 20155954
TI  - Comment on "The concept of protobranching and its many paradigm shifting
      implications for energy evaluations".

PMID- 20155955
TI  - Role of clay minerals in oil-forming reactions.
AB  - Mineral-catalyzed decarboxylation reactions are important in both crude oil
      formation and, increasingly, biofuel production. In this study we examined
      decarboxylation reactions of a model fatty acid, propionic acid, C(2)H(5)COOH, to
      an alkane, C(2)H(6), in a model of pyrophillite with an isomorphic substitution
      of aluminum in the tetrahedral layer. We model a postulated reaction mechanism
      (Almon, W. R.; Johns, W. D. 7th International Meeting on Organic Geochemistry
      1975, Vol. 7) to ascertain the role of Al substitution and a counterion in
      decarboxylation reactions. We employ a periodic cell, planewave, ab initio DFT
      computation to examine the total energies and the frontier orbitals of different
      model sets, including the effects of charge on the reaction, the effect of Al
      substitution, and the role of Na counterions. The results show that an uncharged
      system with a sodium counterion is most feasible for catalyzing the
      decarboxylation reaction in an Al-substituted pyrophillite and, also, that
      analysis of the orbitals is a better indicator of a reaction than charge alone.

PMID- 20155956
TI  - A multireference coupled-cluster study of electronic excitations in furan and
      pyrrole.
AB  - A multireference (MR), general-model-space (GMS), state-universal (SU), coupled
      cluster (CC) method that considers singly (S) and doubly (D) excited cluster
      amplitudes relative to the reference configurations spanning the model space (GMS
      SU CCSD) is employed to investigate a number of low-lying excited states of two
      five-membered, six pi -electron aromatic ring molecules, namely, furan and
      pyrrole. An extended basis set that includes diffuse functions and molecule
      centered Rydberg functions is employed. Computed vertical excitation energies are
      compared with experimental values as well as with other theoretical results,
      namely, those obtained by the equation-of-motion (EOM) CCSD method or,
      equivalently, the symmetry adapted cluster configuration interaction (SAC-CI)
      method, by the MR CI method, by MR perturbation theory, and by other methods
      whenever available. For excited states dominated by single-excitations the GMS SU
      CCSD energies represent an improvement relative to the most closely related EOM
      CCSD results by about 0.1 eV.

PMID- 20155958
TI  - Vibrational circular dichroism and IR absorption spectra of amino acids: a
      density functional study.
AB  - With density functional theory, vibrational circular dichroism (VCD) and infrared
      absorption (IR) spectra are obtained at the B3LYP/CC-pVTZ level of theory for 20
      alpha-amino acids. The contribution of different vibration modes to the IR and
      VCD spectra is analyzed. Overall agreement between calculated results for amino
      acids in gas phase with the available experimental VCD data for matrix-assisted
      amino acid films is found. The analysis of the calculated IR and VCD spectra
      indicates that the functional groups in the backbones and side chains of amino
      acids contribute differently to the spectra line shape. It is obtained that
      molecular torsions are the characteristic vibrations of the amino acids at the
      low-frequency regime, whereas the bending of bond angles, the out-of-plane
      wagging of individual atoms, and some stretching modes dominate the intermediate
      frequency range. Specific modes like NH(2) scissoring, CO bond stretching, and
      the (symmetric and asymmetric) stretching of the hydrogen atoms in the NH(2) and
      OH groups characterize the high-frequency regime. A general trend emerging from
      these calculations indicates that the rho(OH) rocking and nu(C=O) stretching
      modes have the highest intensity in the VCD spectra of most amino acids.

PMID- 20155959
TI  - TDDFT study of the optical properties of Cy5 and its derivatives.
AB  - Cyanine dyes which show a very strong pi-pi* type electronic absorption have
      attracted attention as active components for optoelectronic applications. In the
      present study, the optical properties of Cy5 and Cy5-X (X = F, Cl, Br, and I)
      have been theoretically explored by applying the time-dependent density
      functional theory (TDDFT) method. The geometries of the ground state of the
      studied models have been fully optimized at the B3LYP/LanL2DZ and B3LYP/SDD
      levels of theory. Based upon the optimized structures of the ground state, the
      TDDFT calculations were performed to compute the vertical singlet excitation
      energies and the absorption spectra of the studied species. Compared with the
      optical properties of Cy5, halogen ions lower the vertical excitation energies
      and cause the maximum absorption wavelength to be red-shifted for the Cy5-X
      derivatives. By employing the polarizable continuum model (PCM) approach for all
      the gas-phase-optimized structures, the influence of solvent effects on the
      spectra of Cy5 and Cy5-X was considered in three solvents (ethanol, DMSO, and
      water). The obtained results suggest that the solvents may lower the excitation
      energy of Cy5. However, for the Cy5-X species the excitation energies are higher
      in solvents than in the gas phase.

PMID- 20155960
TI  - Boryl substitution of acetaldehyde makes it an enol: inconsistency between Gn/CBS
      and ab initio/DFT data.
AB  - Tautomerism, a particular case of isomerism, plays an important role in modern
      organic chemistry, biochemistry, medicinal chemistry, pharmacology, and molecular
      biology. Inconsistency between results of complex energy computation methods
      Gn/CBS (G2, G3, CBS-4M, and CBS-QB3) and high-level ab initio/DFT ones
      (CCSD(T)/CBS, MP2/CBS, and B3LYP/aug-cc-pVTZ) is found. Gn/CBS methods provide a
      qualitatively different description of tautomeric (keto-enol) equilibrium in 2
      substituted acetaldehydes. According to valence focal point analysis (FPA) based
      on CCSD(T)/aug-cc-pVTZ, MP3/aug-cc-pVQZ, and MP2/aug-cc-pV5Z energies, boryl
      substitution of acetaldehyde makes it an enol. In other words, enol was found to
      be the global minimum on the potential energy surface (PES) of C(2)H(5)BO. Gn/CBS
      methods predict the keto form to be the minimum. The relative energy of alkenol,
      CH(BH(2))=CH(OH), is calculated to be -1.67 +/- 0.82 kcal mol(-1) at CCSD(T)/CBS
      level of theory. Hydrogen shift effects are also calculated in two other 2
      substituted acetaldehydes, namely, 3-oxopropanenitrile (C(3)H(3)NO) and ethanal
      (C(2)H(4)O), with a general formula of XH(2)C-CHO (X = BH(2), CN, and H).
      Electron density (charge) transfer between the C=C double bond and the free p
      orbital of the boron atom (B) in a boryl group (BH(2)) greatly stabilizes enol
      with respect to ketone, CH(2)(BH(2))-CHO. The first known stabilization of enol
      in an acetaldehyde derivative, without an intramolecular hydrogen bond (H-bond),
      questions the accuracy of complex energy computation methods for boron-containing
      molecules. The possible reasons and consequences of this finding are discussed.

PMID- 20155961
TI  - From tortoise-shell-like molecular segments to C(4n)H(2n)N(2n) (n = 3-8) cages
      stabilized by alkenyl: a theoretical study.
AB  - The C(4n)H(2n)N(2n) (n = 3-8) cage molecules with D(nh) symmetry and their
      nitrated products, C(4n)N(4n)O(4n) (n = 3, 4, 5) and C(4n)H(n)N(3n)O(2n) (n = 4,
      6, 8) were studied by DFT at the B3LYP/cc-pVDZ level. Their geometrical
      structures, ground-state energies, and heats of formation have been investigated.
      They exhibit an obvious cage effect. Hirshfeld partitioning charges in momentum
      space give evidence of high strained energy in the title compounds. Their orbital
      energy and frontier orbital shape and electrostatic potential calculation are
      also studied. Investigation of heat of formation and NICS analysis reveal that
      C(24)H(12)N(12) is the most stable molecule among title compounds with D(nh)
      symmetry. Their half nitrated products are predicted as a promising candidate for
      high energy matter.

PMID- 20155962
TI  - On the electron affinity of nitromethane (CH3NO2).
AB  - A high-level systematic computational study is presented on an accurate value for
      the adiabatic valence electron affinity of nitromethane, CH(3)NO(2), to resolve
      literature disagreements in theoretical and experimental reported values. Density
      functional methods with triple-zeta quality basis sets gave good fortuitous
      agreement to early experimental determinations, while single-reference wave
      function based methods employing up to CCSD(T) gave poor or fortuitous agreement
      depending on the experimental reference value. DFT methods in general cannot
      accurately describe electron attachment from the result of unphysical self
      interaction. It is found that multireference methods with aug-cc-pVTZ or similar
      basis sets are required to converge to an experimental value. Our highest level
      of theory 3S-MCQDPT2 and 7S-MCQDPT2 calculations with an aug-cc-pVTZ quality
      basis description yield values of 0.188 and 0.176 eV (0.170 eV with polynomial
      extrapolation), in excellent agreement with the most recent experimental value of
      0.172 +/- 0.006 eV. CCSD(T)//aug-cc-pVTZ provides a fortuitously reasonable
      description. The isolated dipole-bound anion binding energy is tentatively
      calculated to be 7-8 meV.

PMID- 20155963
TI  - HRMAS 1H NMR conformational study of the resin-bound amyloid-forming peptide
      GNNQQNY from the yeast prion Sup35.
AB  - The conversion of soluble proteins to insoluble amyloid fibrils is associated
      with numerous human diseases. The peptide GNNQQNY is a short segment of the yeast
      prion protein Sup35 that previously has been found to form amyloid fibrils in a
      similar manner to the protein itself. The approach taken in this work was to
      attach this peptide sequence to an insoluble polymer matrix through solid phase
      peptide synthesis and give it the internal freedom to fold into its local
      conformation in an organic solvent. Observation of its monomeric structure, free
      from the effects of aggregation, entropic solvent effects, and neighboring
      molecules, was possible by two-dimensional high-resolution magic angle spinning
      (1)H NMR spectroscopy. Analysis of the through-bond correlations and through
      space interactions observed in the spectra, combined with global energy
      minimization via computational studies, led to the observation that the peptide
      chain adopts a compact beta-like turn at the central hydrophilic residues. The
      technique of peptide attachment to a polymer resin and observation by NMR may
      allow for future study of single peptide fragments prone to aggregation.

PMID- 20155964
TI  - Hydrogen sensing and sensitivity of palladium-decorated single-walled carbon
      nanotubes with defects.
AB  - Individual single-walled carbon nanotubes (SWCNTs) become sensitive to H(2) gas
      when their surfaces are decorated with Pd metal, and previous reports measure
      typical chemoresistive increases to be approximately 2-fold. Here, thousand-fold
      increases in resistance are demonstrated in the specific case where a Pd cluster
      decorates a SWCNT sidewall defect site. Measurements on single SWCNTs, performed
      both before and after defect incorporation, prove that defects have extraordinary
      consequences on the chemoresistive response, especially in the case of SWCNTs
      with metallic band structure. Undecorated defects do not contribute to H(2)
      chemosensitivity, indicating that this amplification is due to a specific but
      complex interdependence between a defect site's electronic transmission and the
      chemistry of the defect-Pd-H(2) system. Dosage experiments suggest a primary role
      is played by spillover of atomic H onto the defect site.

PMID- 20155965
TI  - Excess dissipation in a single-electron box: the Sisyphus resistance.
AB  - We present measurements of the ac response of a single-electron box (SEB). We
      apply a radio frequency signal with a frequency larger than the tunneling rate
      and drive the system out of equilibrium. We observe much more dissipation in the
      SEB then one would expect from a simple circuit model. We can explain this in
      terms of a mechanism that we call the Sisyphus resistance. The Sisyphus
      resistance has a strong gate dependence which can be used for electrometery
      applications.

PMID- 20155966
TI  - Icosahedral crown gold nanocluster au(43)cu(12) with high catalytic activity.
AB  - Structural and catalytic properties of the gold alloy nanocluster Au(43)Cu(12)
      are investigated using a density-functional method. In contrast to the pure
      Au(55) nanocluster, which exhibits a low-symmetry C(1) structure, the 55-atom
      "crown gold" nanocluster exhibits a multishell structure, denoted by
      Au@Cu(12)@Au(42), with the highest icosahedral group-symmetry. In addition,
      density functional calculations suggest that this geometric magic-number
      nanocluster possesses comparable catalytic capability as a small-sized Au(10)
      cluster for the CO oxidation, due in part to their low-coordinated Au atoms on
      vertexes. The gold alloy nanocluster also shows higher selectivity for styrene
      oxidation than the bare Au(111) surface.

PMID- 20155967
TI  - Experimental realization of subradiant, superradiant, and fano resonances in
      ring/disk plasmonic nanocavities.
AB  - Subradiant and superradiant plasmon modes in concentric ring/disk nanocavities
      are experimentally observed. The subradiance is obtained through an overall
      reduction of the total dipole moment of the hybridized mode due to antisymmetric
      coupling of the dipole moments of the parent plasmons. Multiple Fano resonances
      appear within the superradiant continuum when structural symmetry is broken via a
      nanometric displacement of the disk, due to coupling with higher order ring
      modes. Both subradiant modes and Fano resonances exhibit substantial reductions
      in line width compared to the parent plasmon resonances, opening up possibilities
      in optical and near IR sensing via plasmon line shape design.

PMID- 20155968
TI  - Built-in quantum dot antennas in dye-sensitized solar cells.
AB  - A new design of dye-sensitized solar cells involves colloidal semiconductor
      quantum dots that serve as antennas, funneling absorbed light to the charge
      separating dye molecules via nonradiative energy transfer. The colloidal quantum
      dot donors are incorporated into the solid titania electrode resulting in high
      energy transfer efficiency and significant improvement of the cell stability.
      This design practically separates the processes of light absorption and charge
      carrier injection, enabling us to optimize each of these separately. Incident
      photon-to-current efficiency measurements show a full coverage of the visible
      spectrum despite the use of a red absorbing dye, limited only by the efficiency
      of charge injection from the dye to the titania electrode. Time resolved
      luminescence measurements clearly relate this to Forster resonance energy
      transfer from the quantum dots to the dye. The presented design introduces new
      degrees of freedom in the utilization of quantum dot sensitizers for photovoltaic
      cells. In particular, it opens the way toward the utilization of new materials
      whose band offsets do not allow direct charge injection.

PMID- 20155969
TI  - Understanding the sensor response of metal-decorated carbon nanotubes.
AB  - We have explored the room temperature response of metal nanoparticle decorated
      single-walled carbon nanotubes (NP-SWNTs) using a combination of electrical
      transport, optical spectroscopy, and electronic structure calculations. We have
      found that upon the electrochemical growth of Au NPs on SWNTs, there is a
      transfer of electron density from the SWNT to the NP species, and that adsorption
      of CO molecules on the NP surface is accompanied by transfer of electronic
      density back into the SWNT. Moreover, the electronic structure calculations
      indicate dramatic variations in the charge density at the NP-SWNT interface,
      which supports our previous observation that interfacial potential barriers
      dominate the electrical behavior of NP-SWNT systems.

PMID- 20155970
TI  - Tuning the packing density of 2D supramolecular self-assemblies at the solid
      liquid interface using variable temperature.
AB  - The two-dimensional (2D) crystal engineering of molecular architectures on
      surfaces requires controlling various parameters related respectively to the
      substrate, the chemical structure of the molecules, and the environmental
      conditions. We investigate here the influence of temperature on the self-assembly
      of hexakis(n-dodecyl)-peri-hexabenzocoronene (HBC-C(12)) adsorbed on gold using
      scanning tunneling microscopy (STM) at the liquid/solid interface. We show that
      the packing density of 2D self-assembled HBC-C(12) can be precisely tuned by
      adjusting the substrate temperature. Increasing the temperature progressively
      over the 20-50 degrees C range induces three irreversible phase transitions and a
      3-fold increase of the packing density from 0.111 to 0.356 molecule/nm(2). High
      resolution STM images reveal that this 2D packing density increase arises from
      the stepwise desorption of the n-dodecyl chains from the gold surface. Such
      temperature-controlled irreversible phase transitions are thus a versatile tool
      that can then be used to adjust the packing density of highly ordered functional
      materials in view of applications in organic electronic devices.

PMID- 20155971
TI  - Antiviral and anti-inflammatory metabolites from the soft coral Sinularia
      capillosa.
AB  - Chemical investigations of the soft coral Sinularia capillosa resulted in the
      isolation of one new tetraprenylbenzoquinone, capilloquinone (1), two new
      furanobenzosesquiterpenoids, capillobenzopyranol (2) and capillobenzofuranol (3),
      one new furanosesquiterpenoid, capillofuranocarboxylate (4), and five previously
      characterized metabolites, comprising (E)-5-(2,6-dimethylocta-5,7-dienyl)furan-3
      carboxylic acid (5), 2-[(2E,6E)-3,7-dimethyl-8-(4-methylfuran-2-yl)octa-2,6
      dienyl]-5-methylcyclohexa-2,5-diene-1,4-dione (6), 2-[(2E,6E)-3,7-dimethyl-8-(4
      methylfuran-2-yl)octa-2,6-dienyl]-5-methylbenzene-1,4-diol (7), (-)-loliolide
      (8), and 3,4,11-trimethyl-7-methylenebicyclo[6.3.0]undec-2-en-11alpha-ol (9). The
      structures of 1-4 were elucidated through extensive spectroscopic analysis. The
      cytotoxicity, anti-HCMV (human cytomegalovirus) activity, antibacterial activity,
      and anti-inflammatory effects of 1-9 were evaluated in vitro.

PMID- 20155972
TI  - Nitrogen-doped graphene as efficient metal-free electrocatalyst for oxygen
      reduction in fuel cells.
AB  - Nitrogen-doped graphene (N-graphene) was synthesized by chemical vapor deposition
      of methane in the presence of ammonia. The resultant N-graphene was demonstrated
      to act as a metal-free electrode with a much better electrocatalytic activity,
      long-term operation stability, and tolerance to crossover effect than platinum
      for oxygen reduction via a four-electron pathway in alkaline fuel cells. To the
      best of our knowledge, this is the first report on the use of graphene and its
      derivatives as metal-free catalysts for oxygen reduction. The important role of N
      doping to oxygen reduction reaction (ORR) can be applied to various carbon
      materials for the development of other metal-free efficient ORR catalysts for
      fuel cell applications, even new catalytic materials for applications beyond fuel
      cells.

PMID- 20155974
TI  - Practical synthesis of a Cathepsin S inhibitor: route identification,
      purification strategies, and serendipitous discovery of a crystalline salt form.
AB  - A "redox economical" strategy resulted in a concise, modular synthesis of
      compound 1, a potent Cathepsin S inhibitor. Starting from three building blocks,
      crude drug substance was prepared in a two-step sequence in high yield. Efficient
      purification of the crude drug substance was accomplished via the formation of an
      unusual monoethyl oxalate salt.

PMID- 20155975
TI  - Cofacial boron dipyrromethene (Bodipy) dimers: synthesis, charge delocalization,
      and exciton coupling.
AB  - A series of compounds containing two boron dipyrromethene (Bodipy) units has been
      synthesized and fully characterized in which the spacer between the two Bodipy
      groups is varied from dibenzothiophene (BD1), to dibenzofuran (BD2), to 9,9
      dimethylxanthene (BD3), and finally to diphenyl ether (BD4 and BD5). For BD1-BD4
      the Bodipy units adopt, to varying degrees, cofacial conformations that allow for
      systematic variations of both the mutual orientation and the mean separation of
      the two Bodipy residues. In the remaining dimer, BD5, the Bodipy units are well
      separated and cannot come into close proximity. Single-crystal X-ray structures
      have been determined for BD1-BD3 and reveal that the "bite angle" between the two
      Bodipy residues decreases progressively along the series with individual values
      of 41.33(5) degrees, 36.95(6) degrees, and 8.57(3) degrees. Detailed (1)H and
      (19)F NMR studies for BD3 and BD4 show the methylene protons to be diastereotopic
      due to restricted rotation of the two Bodipy groups. For BD4 conformational
      rocking is invoked to explain the variable-temperature NMR spectra, whereby the
      methyl and methylene groups become inequivalent. Cyclic voltammetry indicates
      reversible oxidation and reduction of the Bodipy groups. However, the close
      proximity of the Bodipy groups in BD3 and BD4 results in two well-resolved waves
      in the anodic region, and slight splitting of the cathodic wave. Peak splitting
      is attributed to charge delocalization. Spectroelectrochemical measurements at a
      fixed oxidative potential reveal an optical intervalence charge-transfer (IVCT)
      absorption band. This IVCT band is attributed to electron exchange between the
      cofacially arranged neutral and mono-oxidized Bodipy units. Various levels of
      exciton coupling are observed for BD1-BD4, but not BD5 since here the Bodipy
      groups remain isolated.

PMID- 20155973
TI  - Multifunctional oval-shaped gold-nanoparticle-based selective detection of breast
      cancer cells using simple colorimetric and highly sensitive two-photon scattering
      assay.
AB  - Breast cancer is the most common cancer among women, and it is the second leading
      cause of cancer deaths in women today. The key to the effective and ultimately
      successful treatment of diseases such as cancer is early and accurate diagnosis.
      Driven by the need, in this article, we report for the first time a simple
      colorimetric and highly sensitive two-photon scattering assay for highly
      selective and sensitive detection of breast cancer SK-BR-3 cell lines at a 100
      cells/mL level using a multifunctional (monoclonal anti-HER2/c-erb-2 antibody and
      S6 RNA aptamer-conjugated) oval-shaped gold-nanoparticle-based nanoconjugate.
      When multifunctional oval-shaped gold nanoparticles are mixed with the breast
      cancer SK-BR-3 cell line, a distinct color change occurs and two-photon
      scattering intensity increases by about 13 times. Experimental data with the
      HaCaT noncancerous cell line, as well as with MDA-MB-231 breast cancer cell line,
      clearly demonstrated that our assay was highly sensitive to SK-BR-3 and it was
      able to distinguish from other breast cancer cell lines that express low levels
      of HER2. The mechanism of selectivity and the assay's response change have been
      discussed. Our experimental results reported here open up a new possibility of
      rapid, easy, and reliable diagnosis of cancer cell lines by monitoring the
      colorimetric change and measuring TPS intensity from multifunctional gold
      nanosystems.

PMID- 20155976
TI  - Photocontrol of biological activities of protein by means of a hydrogel.
AB  - Because proteins show high activity and are essential for biological function,
      proteins are important and useful biomolecules; however, it is hard to control
      activities whenever and wherever required. Although some photoactivated proteins
      have been reported to date, such proteins have required a protein-specific design
      and site-specific chemical modification. We have recently developed a method to
      encapsulate proteins within hydrogels that can be photocleaved with ultraviolet
      (UV) light, thus releasing the proteins; we refer to this method as "protein
      activation and release from cage by external light (PARCEL)." Biological
      activities of protein restricted by hydrogel encapsulation were recovered by
      applying external light to the protein-hydrogel. We also used these hydrogels to
      screen selective ligands as therapeutic agents for disease. This innovative
      technique for basic research in biology and biochemistry might also be useful in
      practical or clinical applications, such as biosensing, catalysis, and drug
      delivery.

PMID- 20155977
TI  - Direct quantification of protein-metal ion affinities by electrospray ionization
      mass spectrometry.
AB  - The application of the direct electrospray ionization mass spectrometry (ES-MS)
      assay for quantifying the stoichiometry and absolute affinity of protein-metal
      ion binding in vitro is described. Control ES-MS experiments performed on
      solutions containing calcium chloride or calcium acetate and a pair of proteins
      that do not bind calcium ions in solution revealed that the nonspecific
      association of metal ions to proteins during ES is a random process, independent
      of protein size and structure. These results establish the reliability of the
      reference protein method for quantitatively correcting ES mass spectra for the
      occurrence of nonspecific metal ion binding to proteins during ES-MS analysis. To
      demonstrate the utility of the direct ES-MS assay, when carried out using the
      reference protein method, the calcium binding stoichiometry of bovine alpha
      lactalbumin and the calcium ion affinity of bovine beta-lactoglobulin were
      established.

PMID- 20155978
TI  - Small molecule ambient mass spectrometry imaging by infrared laser ablation
      metastable-induced chemical ionization.
AB  - Presented here is a novel ambient ion source termed infrared laser ablation
      metastable-induced chemical ionization (IR-LAMICI). IR-LAMICI integrates IR laser
      ablation and direct analysis in real time (DART)-type metastable-induced chemical
      ionization for open air mass spectrometry (MS) ionization. The ion generation in
      the IR-LAMICI source is a two step process. First, IR laser pulses impinge the
      sample surface ablating surface material. Second, a portion of ablated material
      reacts with the metastable reactive plume facilitating gas-phase chemical
      ionization of analyte molecules generating protonated or deprotonated species in
      positive and negative ion modes, respectively. The successful coupling of IR
      laser ablation with metastable-induced chemical ionization resulted in an ambient
      plasma-based spatially resolved small molecule imaging platform for mass
      spectrometry (MS). The analytical capabilities of IR-LAMICI are explored by
      imaging pharmaceutical tablets, screening counterfeit drugs, and probing algal
      tissue surfaces for natural products. The resolution of a chemical image is
      determined by the crater size produced with each laser pulse but not by the size
      of the metastable gas jet. The detection limits for an active pharmaceutical
      ingredient (acetaminophen) using the IR-LAMICI source is calculated to be low
      picograms. Furthermore, three-dimensional computational fluid dynamic simulations
      showed improvements in the IR-LAMICI ion source are possible.

PMID- 20155979
TI  - Energy transfer ligands of the GluR2 ligand binding core.
AB  - Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that
      mediate excitatory signaling in the central nervous system. When a ligand binds
      to the extracellular domain of iGluRs, local conformational changes ensue and
      this motion is translated to the transmembrane domain, inducing channel opening.
      We have used an isolated ligand binding domain, GluR2-S1S2J (GluR2), as a model
      system to study the protein-ligand complex by steady-state and time-resolved
      intrinsic tryptophan fluorescence measurements. Specifically, we determined that
      the widely used and structurally characterized antagonist, 6,7-dinitroquinoxaline
      2,3-dione (DNQX), acts as an efficient fluorescence energy transfer (FET)
      acceptor for Trp. Consistent with crystallographic data, our results indicate
      that the four native tryptophans are within Forster's radius (R(o) approximately
      33 A) of the bound ligand. Additionally, we demonstrate the broader value of this
      technique by identifying an original FET ligand, 3-nitrotyrosine (3NY), for GluR2
      (R(o) approximately 24 A; apparent dissociation constant K(d) approximately 170
      microM). Estimated average donor-acceptor (Trp-ligand) distances extracted from
      tryptophan excited-state decays are similar for both ligands (approximately 24
      A), suggesting that 3NY binds in the structurally characterized ligand binding
      cleft. Moreover, an alternative competition assay utilizing Trp --> DNQX
      quenching for detection of ligand binding in GluR2 is described.

PMID- 20155980
TI  - Protein expression profiles of necrosis and apoptosis induced by 5-fluoro-2'
      deoxyuridine in mouse cancer cells.
AB  - We have investigated the molecular mechanisms regulating the necrosis and
      apoptosis that occur on treatment of mouse mammary tumor FM3A cells with 5-fluoro
      2'-deoxyuridine (FUdR), a potent anticancer agent, using the original clone F28-7
      and its variant F28-7-A cells. Previously, we reported an interesting observation
      that FUdR induces a necrotic morphology in F28-7 but an apoptotic morphology in
      F28-7-A cells. We have now analyzed the protein expression profiles of these FUdR
      induced necrosis and apoptosis. Thus, proteome analysis of these clones by two
      dimensional gel electrophoresis and mass spectrometry showed that the cytoplasmic
      intermediate filament protein, cytokeratin-19, is expressed at a significantly
      higher level in F28-7 than in F28-7-A cells. This strong expression was detected
      both in untreated and FUdR-treated stages of F28-7 cells. We interpreted this
      phenomenon as suggesting that cytokeratin-19 possesses a function in leading the
      cell to apoptosis. We performed a knockdown of cytokeratin-19 expression in F28-7
      cells by use of the small interfering RNA technique. Indeed, a lowering of the
      cytokeratin-19 expression down to the level in F28-7-A occurred, and the FUdR
      induced death morphology of this knockdown F28-7 was apoptosis, instead of the
      necrosis usually observable in the FUdR-treated F28-7. It is known that the
      cytoskeletal protein cytokeratin-19 undergoes caspase-mediated degradation during
      apoptosis. Our present finding provides an interesting possibility that
      cytokeratin-19 may have a key role in regulating cell-death morphology.

PMID- 20155981
TI  - A facile approach for the fabrication of highly stable superhydrophobic cotton
      fabric with multi-walled carbon nanotubes-azide polymer composites.
AB  - Homogeneous dispersion and functionalization of pristine multiwalled carbon
      nanotubes (MWNTs) in various organic solvents was achieved by a simple ultrasonic
      process in the presence of an azide copolymer, poly(4-azidophenyl methacrylate-co
      methyl acrylate)(P(APM-co-MA)). The copolymes were noncovalently attached to the
      surface of the MWNTs via pi-pi interactions to form MWNT-P(APM-co-MA) composites.
      The composites were characterized by transmission electron microscopy,
      thermogravimetric analysis, Raman spectra and UV-vis spectra. The solution
      dispersion of the MWNT-P(APM-co-MA) composites were used to prepare
      superhydrophobic cotton fabric by a facile dip-coating approach. MWNTs were
      covalently attached to the surface of the cotton fabric through the chemical
      reactions between the azide groups of P(APM-co-MA) with both MWNTs and cotton
      fibers. The reactions are based on UV-activated nitrene chemistry. Owing to the
      nanoscale roughness introduced by the attachment of MWNTs, the cotton fabric
      surface was transformed from hydrophilic to superhydrophobic with an apparent
      water contact angle of 154 degrees . Since MWNTs were covalently attached on the
      surface of the cotton fabric, the superhydrophobicity possesses high stability
      and chemical durability.

PMID- 20155982
TI  - Mapping the expression of soluble olfactory proteins in the honeybee.
AB  - Chemical communication in insects is mediated by soluble binding proteins,
      belonging to two large families, Odorant-binding Proteins (OBPs) and Chemosensory
      Proteins (CSPs). Recently, evidence has been provided that OBPs are involved in
      recognition of chemical stimuli. We therefore decided to investigate the
      expression of OBPs and CSPs in the honeybee at the protein level, using a
      proteomic approach. Our results are in agreement with previous reports of
      expression at the RNA level and show that 12 of the 21 OBPs predicted in the
      genome of the honeybee Apis mellifera and 2 of the 6 CSPs are present in the
      foragers' antennae, while the larvae express only three OBPs and a single CSP.
      MALDI mass spectrometry on crude antennal extracts and MALDI profiling on
      sections of antennae demonstrated that these techniques can be applied to
      investigate individual differences in the expression of abundant proteins, such
      as OBPs and CSPs, as well as to detect the presence of proteins in different
      regions of the antenna. Finally, as part of a project aimed at the
      characterization of all OBPs and CSPs of the honeybee, we expressed 5 OBPs and 4
      CSPs in a bacterial system and measured their affinity to a number of ligands.
      Clear differences in their binding spectra have been observed between OBPs, as
      well as CSPs.

PMID- 20155983
TI  - Effect of surfactant architecture on the properties of polystyrene
      montmorillonite nanocomposites.
AB  - A series of surfactants were designed and synthesized for use as clay
      modification reagents to investigate the impact of their chemical structure on
      the nanocomposites morphology obtained following polymerization. The behavior of
      the surfactant-modified clays at three different stages were investigated: after
      ion exchange, following dispersion in styrene monomer, and once polymerization
      was complete. The propensity of the styrene monomer to swell the surfactant
      modified clay was observed to be a useful indicator of compatibility and
      predictor of the resultant polystyrene nanocomposite morphology which was
      directly observed using small-angle X-ray scattering (SAXS) and cryogenic
      transmission electron microscopy (TEM). It was found that the key components of
      surfactant design driving exfoliated morphologies were (1) the position of the
      ammonium group, (2) the inclusion of a polymerizable group, (3) the solubility of
      the surfactant in the monomer, (4) the length of the alkyl chain, and (5)
      sufficient concentration of surfactant used to exchange the clay. This
      understanding should lead to better design of clay modifications for use in
      polymer nanocomposites.

PMID- 20155984
TI  - On the thermal stability of surface-assembled viral-metal nanoparticle complexes.
AB  - Biological supramolecules offer attractive templates for nanoparticle synthesis
      and nanodevice fabrication because of their precise size and shape. Viruses in
      particular have gained significant attention in nanodevice fabrication for
      applications such as nanoelectronics, batteries, catalysis, and sensing. However,
      the performance range of these viral-nanoparticle complexes is not well known
      because of the lack of fundamental studies on their properties. In this work, we
      employ in situ grazing incidence small-angle X-ray scattering (GISAXS) to examine
      the thermal stability of viral-nanoparticle complexes composed of tobacco mosaic
      virus (TMV) and palladium nanoparticles. Specifically, we show that the stability
      of the Pd nanoparticles on TMV is significantly enhanced as compared to that of
      particles on the solid substrate surface. Furthermore, we show that the
      agglomeration of Pd nanoparticles and the degradation of the TMV templates are
      coupled and occur simultaneously. These results demonstrate a potent methodology
      toward the in situ analysis of subtle changes in viral-nanoparticle complexes in
      dynamic environments. We envision that the results and methodology demonstrated
      in this study could be applied to better understand the properties and dynamic
      behaviors of organic-inorganic hybrid materials and nanodevices in various
      applications.

PMID- 20155985
TI  - Enhanced tumor cell isolation by a biomimetic combination of E-selectin and anti
      EpCAM: implications for the effective separation of circulating tumor cells
      (CTCs).
AB  - The selective detection of circulating tumor cells (CTCs) is of significant
      clinical importance for the clinical diagnosis and prognosis of cancer
      metastasis. However, largely because of the extremely low number of CTCs (as low
      as 1 in 10(9) hematologic cells) in the blood of patients, effective detection
      and separation of the rare cells remain a tremendous challenge. Cell rolling is
      known to play a key role in physiological processes such as the recruitment of
      leukocytes to sites of inflammation and selectin-mediated CTC metastasis.
      Furthermore, because CTCs typically express the epithelial-cell adhesion molecule
      (EpCAM) on the surface whereas normal hematologic cells do not, substrates with
      immobilized antibody against EpCAM may specifically interact with CTCs. In this
      article, we created biomimetic surfaces functionalized with P- and E-selectin and
      anti-EpCAM that induce different responses in HL-60 (used as a model of
      leukocytes in this study) and MCF-7 (a model of CTCs) cells. HL-60 and MCF-7
      cells showed different degrees of interaction with P-/E-selectin and anti-EpCAM
      at a shear stress of 0.32 dyn/cm(2). HL-60 cells exhibited rolling on P-selectin
      immobilized substrates at a velocity of 2.26 +/- 0.28 microm/s whereas MCF-7
      cells had no interaction with the surface. Both cell lines, however, had
      interactions with E-selectin, and the rolling velocity of MCF-7 cells (4.24 +/-
      0.31 microm/s) was faster than that of HL-60 cells (2.12 +/- 0.15 microm/s).
      However, only MCF-7 cells interacted with anti-EpCAM-coated surfaces, forming
      stationary binding under flow. More importantly, the combination of the rolling
      (E-selectin) and stationary binding (anti-EpCAM) resulted in substantially
      enhanced separation capacity and capture efficiency (more than 3-fold
      enhancement), as compared to a surface functionalized solely with anti-EpCAM that
      has been commonly used for CTC capture. Our results indicate that cell-specific
      detection and separation may be achieved through mimicking the biological
      processes of combined dynamic cell rolling and stationary binding, which will
      likely lead to a CTC detection device with significantly enhanced specificity and
      sensitivity without a complex fabrication process.

PMID- 20155986
TI  - Binding of functionalized paramagnetic nanoparticles to bacterial
      lipopolysaccharides and DNA.
AB  - Magnetite and metallic cobalt-based nanoparticles with sizes ranging from 10 to
      300 nm and surface-functionalized with poly(hexamethylene biguanide) (PHMBG) are
      introduced as capable lipopolysaccharide (LPS)-sequestering agents. The
      nanoparticles efficiently bind to whole E. coli cells and can be used to separate
      the cells effectively from suspension using a magnet. A fluorescence dye
      displacement assay shows strong affinities of the nanoparticles for lipid A, the
      glycolipid component of LPS responsible for septic shock. The particle-lipid A
      affinity is of the same order of magnitude or higher than that of polymyxin B.
      The affinity of smaller (< 50 nm) magnetite particles modified with PHMBG to
      lipid A is several-fold higher than that of their larger counterparts (> 100 nm)
      due to their higher surface area to volume ratio. The nanoparticles possess high
      saturation capacity for double-stranded lambdaDNA from E. coli, with which
      particle-polyelectrolyte complexes are formed. The PHMBG-modified nanoparticles
      are potent bactericides, inhibiting E. coli viability and growth at
      concentrations at < or = 10 microg/mL.

PMID- 20155987
TI  - Does functional outcome in acute ischaemic stroke patients correlate with the
      amount of free-radical scavenger treatment? A retrospective study of edaravone
      therapy.
AB  - BACKGROUND: Edaravone is a free-radical scavenger that has been widely used for
      acute ischaemic stroke in Japan. However, the optimal total dosage of edaravone
      has not been established. OBJECTIVE: To clarify the relationship between the gain
      in functional recovery (rehabilitation gain) and the total amount of edaravone
      used for acute-phase therapy for cerebral infarction at a convalescent
      rehabilitation hospital. We also sought to determine if there were differences in
      outcome between stroke subtypes. METHODS: Medical records were retrospectively
      surveyed to identify patients who had received edaravone treatment for acute
      phase cerebral infarction at Kawakita General Hospital, Tokyo, Japan, followed by
      recovery rehabilitation at Kawakita Rehabilitation Hospital, Tokyo, Japan, for >
      or = 30 days. Edaravone was initiated within 24 hours of stroke onset, and was
      administered as a 30 mg (1 ampoule) continuous intravenous infusion twice daily
      for up to 14 days. Patients were stratified into tertiles based on the total
      amount of edaravone used (measured in ampoules) during the acute phase (i.e.
      administration duration). Rehabilitation gain was defined as the change
      (increase) from convalescent rehabilitation hospital admission to discharge in
      the Functional Independence Measure-Motor (DeltaFIM-M) or Barthel Index (DeltaBI)
      score. RESULTS: Of the 72 enrolled patients, 21 belonged to the lower (short
      term) tertile (0-14 ampoules), 27 to the middle (medium-term) tertile (15-23
      ampoules) and 24 to the upper (long-term) tertile (24-33 ampoules) groups. There
      was no correlation between the total amount of edaravone used and the length of
      stay at an acute-phase hospital. However, a significant correlation was seen
      between the total amount of edaravone used and DeltaFIM-M (adjusted regression
      coefficient 0.81; p = 0.003) and DeltaBI (0.88; p = 0.005) score in patients with
      cardioembolic stroke; no significant correlation was seen in other stroke
      subtypes. Cardioembolic stroke patients also showed improvements in both FIM-M
      and BI score as the total amount of edaravone used increased. The difference
      between the short- and long-term group was 10.1 (95% CI 2.3, 17.8) for DeltaFIM-M
      score, and 12.0 (95% CI 2.8, 21.2) for DeltaBI score. Patients with
      atherothrombotic stroke showed a similar tendency with respect to DeltaBI score.
      CONCLUSION: Edaravone dose-dependently increases rehabilitation gain according to
      DeltaFIM-M and DeltaBI scores in patients with cardioembolic stroke, and a
      similar trend was also observed with respect to DeltaBI score in patients with
      atherothrombotic stroke. This suggests that the total amount of edaravone used is
      associated with its efficacy for rehabilitation gain.

PMID- 20155988
TI  - Efficacy and safety of ezetimibe for Japanese patients with dyslipidaemia: The
      ESSENTIAL Study.
AB  - BACKGROUND: There are insufficient data available on the efficacy and safety of
      lipid-lowering therapy for patients with dyslipidaemia complicated by multiple
      metabolic abnormalities. OBJECTIVE: This study aimed to examine the efficacy and
      safety of ezetimibe 10 mg/day administered to Japanese patients with
      dyslipidaemia. METHODS: This was a prospective study carried out at Kyushu
      University Hospital, Fukuoka, Japan. In one group, ezetimibe 10 mg/day alone was
      given to 33 patients for 12 weeks. In the other two groups, ezetimibe was given
      with an HMG-CoA reductase inhibitor (statin) to 13 patients for 12 weeks:
      pravastatin 10 mg/day (n = 7) or rosuvastatin 2.5 mg/day (n = 6). The main
      outcome measure was the effect of ezetimibe on low-density lipoprotein
      cholesterol (LDL-C) and other lipid levels from baseline to 12 weeks. RESULTS:
      After 12 weeks of treatment, all groups showed marked reductions in mean +/- SD
      LDL-C level (from 155.4 +/- 22.0 mg/dL at baseline to 118.0 +/- 28.1 mg/dL, i.e. 
      37.4 mg/dL; p < 0.001). The mean reduction in LDL-C level with ezetimibe
      monotherapy was significantly greater in patients with impaired LDL-C metabolism,
      glucose metabolism or hypertension than in those without such abnormalities (
      21.0% vs -8.4%, p < 0.01; -22.7% vs -9.5%, p < 0.05; and -22.5% vs -5.9%, p <
      0.05; respectively). The reduction in LDL-C levels with ezetimibe monotherapy was
      also correlated with the number of metabolic abnormalities (rho = 0.426, p =
      0.013). CONCLUSIONS: Both ezetimibe monotherapy and combination therapy with
      ezetimibe and a statin were able to safely and effectively control LDL-C levels
      in Japanese patients with dyslipidaemia, including those with metabolic
      abnormalities.

PMID- 20155989
TI  - The burden of disrupting gastro-oesophageal reflux disease: a database study in
      US and European cohorts.
AB  - BACKGROUND: Recent data indicate that among patients with gastro-oesophageal
      reflux disease (GORD) there is a subgroup with a higher disrupting burden of
      illness in terms of symptom frequency and overall impact. OBJECTIVE: The aim of
      this study was to evaluate the burden of disrupting versus non-disrupting GORD on
      individuals, healthcare providers and society. METHODS: Data were obtained from
      European (France, Germany, Italy, Spain and the UK) and US respondents in the
      2007 National Health and Wellness Survey (NHWS). Respondents with GORD were
      classified as having disrupting or non-disrupting GORD based on self-reported
      symptom frequency, presence of night-time symptoms and medication usage.
      Disrupting GORD was defined as the presence of GORD symptoms on at least 2
      days/week in addition to either night-time symptoms or use of prescribed/over-the
      counter medication at least twice a week during the past month. RESULTS: Of 116
      536 respondents included in the 2007 NHWS, 23% reported GORD symptoms; 39% of
      these were acknowledged as having disrupting GORD. These patients had higher
      healthcare resource utilization than those with non-disrupting disease.
      Respondents with disrupting GORD also had poorer health-related quality of life,
      greater impairments in health-related work productivity and absenteeism (all p <
      0.05 vs non-disrupting GORD), and higher associated total medical costs. Overall,
      patients with physician-diagnosed GORD also had significantly lower health
      related quality of life than self-diagnosed respondents (p < 0.05). CONCLUSIONS:
      GORD is a common disease that places a substantial burden on affected individuals
      and society. A high proportion of patients have disrupting GORD, which has
      significant adverse potential from both a clinical and an economic perspective.

PMID- 20155990
TI  - Hospitalization for severe bacterial infections in children after exposure to
      NSAIDs: a prospective adverse drug reaction reporting study.
AB  - BACKGROUND: NSAIDs are widely used to treat fever and pain in children, but their
      possible role in the progression of some bacterial infections is controversial.
      OBJECTIVE: This study was performed to analyse reported cases of severe bacterial
      infection associated with NSAID exposure in children admitted for this reason to
      a general paediatric department. METHODS: This study was based on the reporting
      system of hospital admissions for severe bacterial infections in children after
      NSAID exposure, and followed the recommendations of the European Guidelines of
      Pharmacovigilance for medicines used in a paediatric population. Data were
      prospectively collected and reported by active daily surveillance in the
      department from November 2002 to November 2005. RESULTS: Thirty-two cases of
      severe bacterial infections (cellulitis, soft tissue abscesses, parapneumonic
      empyema, necrotizing pneumonia, adenophlegmon [fever and a tender, warm and
      easily compressible neck mass] and lateral or retropharyngeal abscesses) were
      identified in children who had received NSAIDs, principally ibuprofen, in an
      exposure window of 15 days before the beginning of the signs of infection.
      Staphylococcus aureus, group A streptococci and Streptococcus pneumoniae were
      identified. Seven (22%) children required surgical treatment, and four (13%) were
      hospitalized in an intensive care unit. CONCLUSIONS: The frequency of
      hospitalization for severe bacterial infection as a possible adverse effect of
      NSAID use was 0.6% (95% CI 0.4, 0.9) of all admissions during the study period.
      The frequency of severe bacterial infections after exposure to NSAIDs was
      elevated (one case per month) in the department studied. Further work is
      necessary to confirm these findings, given the potential for recruitment and
      protopathic biases in our study.

PMID- 20155991
TI  - Predictors of early worsening after switch to aripiprazole: a randomized,
      controlled, open-label study.
AB  - BACKGROUND: Despite the increasing evidence relating to strategies for switching
      between different antipsychotics, little evidence is available about predictors
      of improvement or worsening while switching. In a previous study, we compared
      different options for switching to aripiprazole and found that patients with
      schizophrenia switched to aripiprazole with immediate discontinuation of the
      previous antipsychotic showed an increase in symptom severity after 1 week.
      OBJECTIVE: To identify predictors of worsening in the first 4 weeks after the
      switch to aripiprazole in partial non-responders to previous treatments. METHODS:
      This was a 12-week randomized, controlled, open-label study that was carried out
      in the Department of Psychiatry of the Catholic University of Korea, Seoul,
      Korea. The study included 77 patients with schizophrenia whose symptoms were not
      optimally controlled and/or who did not tolerate their current antipsychotic
      medications well. Patients were randomly assigned to one of three different
      strategies for switching to aripiprazole 10 mg, i.e.: (i) simultaneous
      discontinuation of the current antipsychotic; (ii) tapering off the current
      antipsychotic over 4 weeks with half the dose after the first 2 weeks; or (iii)
      tapering off the current antipsychotic over 4 weeks after maintenance of the
      current dose for 2 weeks. The main outcome measure was the difference in Brief
      Psychiatric Rating Scale (BPRS) scores from baseline to weeks 1, 2 and 4.
      RESULTS: Baseline severity of disease, as measured by the Clinical Global
      Impression-Severity Scale, BPRS and Schedule for the Assessment of Negative
      Symptoms, significantly predicted worsening at weeks 1, 2 and 4. Specifically,
      lesser disease severity at baseline significantly predicted worsening after
      switching to aripiprazole. CONCLUSION: Patients with relatively mild illness
      severity might be more susceptible to early worsening of symptoms when switched
      to aripiprazole. However, the limitations of the present study, including a small
      sample size, absence of a control group designed to control for nonspecific
      factors such as regression to the mean, and implementation of a switching
      strategy that included only aripiprazole, mean the present findings should be
      considered with caution and further research is needed.

PMID- 20155992
TI  - Incorporating BCNU wafers into malignant glioma treatment: European case studies.
AB  - Carmustine (BCNU: N,N'-bis[2-chloroethyl]-N-nitrosourea) wafers are a local
      chemotherapeutic agent for the treatment of malignant glioma. They avoid the
      problems of high toxicity and short half-life associated with systemic delivery,
      and can bridge the traditional 'treatment gap' between surgery and subsequent
      conventional chemo- or radiotherapy. Clinical trials have demonstrated
      significant improvements in survival and quality of life for patients after
      complete tumour resection and BCNU wafer implantation. In practice, clinicians
      may use BCNU wafers in conjunction with other radio- and chemotherapies, in order
      to maximize the chance of a beneficial patient outcome. The purpose of these case
      reports is to exemplify how four experienced European clinicians employ BCNU
      wafers for the management of malignant glioma, and to illustrate how BCNU wafers
      can be effectively incorporated into treatment regimens. Four patients are
      described in whom BCNU wafers were implanted during the course of treatment for
      glioblastoma multiforme, the most severe and common type of malignant glioma.
      These include three patients with recurrent disease, and a single patient with a
      newly diagnosed tumour. All four patients received additional radio- and
      chemotherapy as appropriate. Treatment was well tolerated and patient survival
      from diagnosis ranged from 56 to 132 weeks. This compared favourably with the
      survival of approximately 58 weeks seen in the recent EORTC-NCIC clinical trial
      of combined radiotherapy with concomitant and adjuvant temozolomide. BCNU wafers
      are an effective means of increasing survival and quality of life in patients
      diagnosed with malignant glioma, and are a valuable addition to the overall
      multimodal treatment strategy for these tumours.

PMID- 20155993
TI  - Atorvastatin-induced prolonged cholestasis with bile duct damage.
AB  - We report a case of acute-onset, long-lasting cholestasis induced by
      atorvastatin. This antihyperlipidaemic drug was taken for 40 days by a 72-year
      old male as a treatment for his mixed dyslipidaemia. At that point, the patient
      presented with asthenia, nausea, painless icterus, acholic stools and
      hyperchromic urine with biochemical analyses showing a dramatic increase in
      bilirubin (total bilirubin 22 mg/dL; direct bilirubin 21 mg/dL) and alkaline
      phosphatase (up to 4-fold over the normal level) with less marked increases in
      transaminases. Liver histology showed a pattern of cholestasis with evident signs
      of cholangiolitis and damage of the interlobular bile ducts. Serum transaminase
      and bilirubin levels returned to normal within 5 months after atorvastatin
      withdrawal while alkaline phosphatase normalized after only 8 months. Scores on
      both the Maria and Victorino clinical scale for the diagnosis of drug-induced
      hepatitis and the Naranjo Adverse Drug Reaction Probability Scale indicated that
      atorvastatin was the probable cause of prolonged cholestasis in this patient.
      This is a rare case of cholestasis probably caused by atorvastatin and unusually
      characterized by bile duct damage.

PMID- 20155994
TI  - Gene therapy in Parkinson's disease: rationale and current status.
AB  - Parkinson's disease is the second most common age-related neurodegenerative
      disorder, typified by the progressive loss of substantia nigra pars compacta
      dopamine neurons and the consequent decrease in the neurotransmitter dopamine.
      Patients exhibit a range of clinical symptoms, with the most common affecting
      motor function and including resting tremor, rigidity, akinesia, bradykinesia and
      postural instability. Current pharmacological interventions are palliative and
      largely aimed at increasing dopamine levels through increased production and/or
      inhibition of metabolism of this key neurotransmitter. The gold standard for
      treatment of both familial and sporadic Parkinson's disease is the peripheral
      administration of the dopamine precursor, levodopa. However, many patients
      gradually develop levodopa-induced dyskinesias and motor fluctuations. In
      addition, dopamine enhancement therapies are most useful when a portion of the
      nigrostriatal pathway is intact. Consequently, as the number of substantia nigra
      dopamine neurons and striatal projections decrease, these treatments become less
      efficacious. Current translational research is focused on the development of
      novel disease-modifying therapies, including those utilizing gene therapeutic
      approaches. Herein we present an overview of current gene therapy clinical trials
      for Parkinson's disease. Employing either recombinant adeno-associated virus type
      2 (rAAV2) or lentivirus vectors, these clinical trials are focused on three
      overarching approaches: augmentation of dopamine levels via increased
      neurotransmitter production; modulation of the neuronal phenotype; and
      neuroprotection. The first two therapies discussed in this article focus on
      increasing dopamine production via direct delivery of genes involved in
      neurotransmitter synthesis (amino acid decarboxylase, tyrosine hydroxylase and
      GTP [guanosine triphosphate] cyclohydrolase 1). In an attempt to bypass the
      degenerating nigrostriatal pathway, a third clinical trial utilizes rAAV2 to
      deliver glutamic acid decarboxylase to the subthalamic nucleus, converting a
      subset of excitatory neurons to GABA-producing cells. In contrast, the final
      clinical trial is aimed at protecting the degenerating nigrostriatum by striatal
      delivery of rAAV2 harbouring the neuroprotective gene, neurturin. Based on
      preclinical studies, this gene therapeutic approach is posited to slow disease
      progression by enhancing neuronal survival. In addition, we discuss the outcome
      of each clinical trial and discuss the potential rationale for the marginal yet
      incremental clinical advancements that have thus far been realized for
      Parkinson's disease gene therapy.

PMID- 20155995
TI  - Metformin for atypical antipsychotic-induced weight gain and glucose metabolism
      dysregulation: review of the literature and clinical suggestions.
AB  - Individuals receiving certain atypical antipsychotic medications are at risk of
      gaining weight and developing metabolic problems. There are no established drug
      treatments to prevent or counter these problems. However, the antihyperglycaemic
      agent metformin appears promising in some recent studies and we review the
      literature that evaluates metformin for limiting or reversing atypical
      antipsychotic drug-induced weight gain and glucose metabolism dysregulation.
      These studies suggest that metformin is beneficial if started early in
      antipsychotic drug treatment. Metformin has also been shown to prevent or delay
      the onset of type 2 diabetes mellitus in high-risk individuals from the general
      population. Based on these findings, we identify antipsychotic drug-treated
      patients who might benefit from metformin therapy and offer clinical guidelines
      for its use. Further long-term studies are needed to extend our observations and
      improve this strategy.

PMID- 20155997
TI  - Intramuscular paliperidone palmitate.
AB  - Intramuscular paliperidone palmitate is a long-acting, atypical antipsychotic
      that is indicated in the US for the acute and maintenance therapy of adult
      patients with schizophrenia. Paliperidone is the major active metabolite of
      risperidone. The noninferiority of flexible doses of intramuscular paliperidone
      palmitate 39-156 mg to flexible doses of intramuscular long-acting risperidone 25
      50 mg was not established in an initial 53-week study. However, these data were
      utilized to optimize the intramuscular paliperidone palmitate dosage regimen. In
      four randomized, double-blind studies, intramuscular paliperidone palmitate 39
      234 mg was generally effective in the treatment of adult patients with acute
      schizophrenia, inducing significantly greater improvements from baseline in the
      mean Positive and Negative Syndrome Scale (PANSS) total score than placebo
      (primary endpoint). In general, intramuscular paliperidone palmitate recipients
      achieved significantly better outcomes than placebo recipients with regard to the
      PANSS subscale, PANSS factor, Personal and Social Performance scale and Clinical
      Global Impressions-Severity scale scores. As maintenance therapy, intramuscular
      paliperidone palmitate 39-156 mg was significantly more effective than placebo in
      delaying the time to the first relapse of schizophrenia symptoms in adult
      patients, according to the results of a randomized, double-blind study. The
      beneficial effects of intramuscular paliperidone palmitate therapy on the PANSS
      total score were sustained in a 52-week noncomparative extension phase of the
      maintenance therapy study. Intramuscular paliperidone palmitate 39-234 mg was
      generally well tolerated in adult patients with schizophrenia.

PMID- 20155996
TI  - The efficacy of Hypericum perforatum (St John's wort) for the treatment of
      premenstrual syndrome: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Premenstrual syndrome (PMS) is a common condition. Some of the most
      widely prescribed medications are selective serotonin reuptake inhibitors
      (SSRIs), based on the hypothesized role of serotonin in the production of PMS
      symptoms. PMS sufferers, especially those experiencing mild to moderate symptoms,
      are often reluctant to take this form of medication and instead buy over-the
      counter preparations to treat their symptoms, for which the evidence base with
      regard to efficacy is limited. Hypericum perforatum (St John's wort) influences
      the serotonergic system. As such, this widely available herbal remedy deserves
      attention as a PMS treatment. OBJECTIVE: To investigate the effectiveness of
      Hypericum perforatum on symptoms of PMS. STUDY DESIGN: This randomized, double
      blind, placebo-controlled, crossover study was conducted between November 2005
      and June 2007. SETTING: Institute of Psychological Sciences, University of Leeds,
      Leeds, UK. PARTICIPATION: 36 women aged 18-45 years with regular menstrual cycles
      (25-35 days), who were prospectively diagnosed with mild PMS. INTERVENTION: Women
      who remained eligible after three screening cycles (n = 36) underwent a two-cycle
      placebo run-in phase. They were then randomly assigned to receive Hypericum
      perforatum tablets 900 mg/day (standardized to 0.18% hypericin; 3.38% hyperforin)
      or identical placebo tablets for two menstrual cycles. After a placebo-treated
      washout cycle, the women crossed over to receive placebo or Hypericum perforatum
      for two additional cycles. MAIN OUTCOME MEASURES: Symptoms were rated daily
      throughout the trial using the Daily Symptom Report. Secondary outcome measures
      were the State Anxiety Inventory, Beck Depression Inventory, Aggression
      Questionnaire and Barratt Impulsiveness Scale. Plasma hormone (follicle
      stimulating hormone [FSH], luteinizing hormone [LH], estradiol, progesterone,
      prolactin and testosterone) and cytokine (interleukin [IL]-1beta, IL-6, IL-8,
      interferon [IFN]-gamma and tumour necrosis factor [TNF]-alpha) levels were
      measured in the follicular and luteal phases during Hypericum perforatum and
      placebo treatment. RESULTS: Hypericum perforatum was statistically superior to
      placebo in improving physical and behavioural symptoms of PMS (p < 0.05). There
      were no significant effects of Hypericum perforatum compared with placebo
      treatment for mood- and pain-related PMS symptoms (p > 0.05). Plasma hormone
      (FSH, LH, estradiol, progesterone, prolactin and testosterone) and cytokine (IL
      1beta, IL-6, IL-8, IFNgamma and TNFalpha) levels, and weekly reports of anxiety,
      depression, aggression and impulsivity, also did not differ significantly during
      the Hypericum perforatum and placebo cycles (p > 0.05). CONCLUSION: Daily
      treatment with Hypericum perforatum was more effective than placebo treatment for
      the most common physical and behavioural symptoms associated with PMS. As
      proinflammatory cytokine levels did not differ significantly between Hypericum
      perforatum and placebo treatment, these beneficial effects are unlikely to be
      produced through this mechanism of action alone. Further work is needed to
      determine whether pain- and mood-related PMS symptoms benefit from longer
      treatment duration. Trial registration number (International Standard Randomised
      Controlled Trial Number Register) ISRCTN31487459.

PMID- 20155998
TI  - Olanzapine/fluoxetine: a review of its use in patients with treatment-resistant
      major depressive disorder.
AB  - Olanzapine/fluoxetine (Symbyax) is an oral, once-daily, fixed-dose combination of
      the atypical antipsychotic olanzapine and the selective serotonin reuptake
      inhibitor (SSRI) fluoxetine. It is indicated, in adult patients, for the acute
      treatment of depressive episodes associated with bipolar I disorder and treatment
      resistant major depressive disorder. In adult patients with treatment-resistant
      depression (major depressive disorder in adults who do not respond to two
      separate trials of different antidepressants of adequate dose and duration in the
      current episode), olanzapine plus fluoxetine combination therapy was generally
      more effective than either drug as monotherapy based on an integrated analysis of
      clinical trials of 8-12 weeks' duration. More limited data also indicate that
      longer-term treatment for 76 weeks with olanzapine plus fluoxetine was
      efficacious in this patient group. Combination therapy was generally well
      tolerated, with a tolerability profile similar to that of olanzapine monotherapy,
      although fluoxetine monotherapy was generally better tolerated than olanzapine
      plus fluoxetine. The combination of olanzapine plus fluoxetine, as a fixed-dose
      formulation, offers a useful treatment option in this difficult-to-treat patient
      group.

PMID- 20155999
TI  - Spotlight on cerebrolysin in dementia.
AB  - Cerebrolysin is a parenterally administered, porcine brain-derived peptide
      preparation that has pharmacodynamic properties similar to those of endogenous
      neurotrophic factors. In several randomized, double-blind trials of up to 28
      weeks' duration in patients with Alzheimer's disease, Cerebrolysin was superior
      to placebo in improving global outcome measures and cognitive ability. A large,
      randomized comparison of Cerebrolysin, donepezil or combination therapy showed
      beneficial effects on global measures and cognition for all three treatment
      groups compared with baseline. Although not as extensively studied in patients
      with vascular dementia, Cerebrolysin has also shown beneficial effects on global
      measures and cognition in this patient population. Cerebrolysin was generally
      well tolerated in clinical trials, with dizziness (or vertigo) being the most
      frequently reported adverse event. Although further studies with Cerebrolysin,
      including longer term trials and further exploration of its use in combination
      with cholinesterase inhibitors, are needed to more clearly determine its place in
      the management of Alzheimer's disease and vascular dementia, available data
      suggest that Cerebrolysin is a useful addition to the treatment options available
      for dementia.

PMID- 20156000
TI  - Reducing patient harm with the use of fentanyl transdermal system.
AB  - Fentanyl transdermal system is indicated for the management of persistent,
      moderate-to-severe chronic pain that requires continuous opioid administration
      for an extended period of time and cannot be managed by other means such as
      nonsteroidal analgesics, opioid combination products, or immediate-release
      opioids. The Institute for Safe Medication Practices and other patient safety
      advocates have long been concerned that transdermal fentanyl is often prescribed,
      dispensed, and administered without proper consideration of patient selection
      criteria, starting-dose recommendations, contraindications, dose adjustment
      recommendations, and safe administration procedures. This article will highlight
      errors that may arise during the use of fentanyl patches and provide risk
      reduction recommendations for consultant pharmacists to address the potential for
      error and patient harm.

PMID- 20156001
TI  - Removing the feeding tube: a procedure with a contentious past.
AB  - When tragic circumstances force families to focus on an individual's right to
      refuse treatment, society is forced to reexamine its views on life and death;
      these circumstances may result in legal rulings and state statutes. During media
      coverage of high-profile cases, reporters frequently used distinct terms like
      "brain dead," "persistent vegetative state," and coma interchangeably, but they
      are clinically different. Today, most bioethicists believe the right to refuse
      treatment is legally and ethically settled, but decision-making in individual
      circumstances often may remain less clear and emotionally charged. Even in the
      best situations, abatement of nutrition during the end-stage of illness continues
      to be difficult, often colored by religious, cultural, and racial or ethnic
      perspectives. Decision-making to withhold or withdraw feeding tubes for younger
      patients is even more difficult and raises many additional questions. Once a
      decision to withdraw a feeding tube is made, clinicians and the patient's loved
      ones need to know what to expect.

PMID- 20156002
TI  - A treatment algorithm for neuropathic pain: an update.
AB  - OBJECTIVE: The purpose of this review is to provide an update of the neuropathic
      pain treatment algorithm previously published by Namaka et al. in 2004. This
      algorithm focuses on the strategic incorporation of the latest pain therapies
      while providing an update of any recent developments involving medications
      previously listed in the algorithm. DATA SOURCES: PubMed, MEDLINE, Cochrane, and
      Toxnet databases were used to conduct all literature searches on neuropathic pain
      and targeted treatment strategies. Comprehensive search efforts in the identified
      databases included studies published between 1980 and 2009. The search term
      "neuropathic pain" was used along with each of the agents outlined in this
      review: pregabalin, paroxetine CR, duloxetine, tramadol XL, Tramacet, Sativex,
      and nabilone. STUDY SELECTION: A total of 90 studies were reviewed and selected
      based on level 1, 2, and 3 search strategies. DATA EXTRACTION: Level 1 search
      strategies were initially aimed at evidence-based trials of large sample size (N
      > 100), with a randomized, double-blind, placebo-controlled design conducted by
      investigators well versed in the specialty area of interest. A level 2 search was
      conducted for additional trials that had many, but not all, of the desirable
      traits of evidence-based trials. In addition, a level 3 search strategy was
      conducted to compare key findings stated in anecdotal reports of very small (N <
      15), poorly designed trials with the results of well-designed, evidence-based
      trials identified in level 1 and/or level 2 searches. DATA SYNTHESIS: Based on a
      thorough evaluation of the literature, pregabalin, paroxetine CR, and duloxetine
      have been placed in the updated algorithm as first-line agents, while tramadol
      XL, Tramacet, Sativex, and nabilone function primarily as adjunctive agents.
      CONCLUSION: The updated algorithm provides a baseline framework from which
      clinicians can justify the medication they prescribe.

PMID- 20156003
TI  - Prevention and treatment of cardioembolic stroke: a case study.
AB  - Ischemic stroke is a medical emergency that requires immediate evaluation and
      treatment. During the acute phase following stroke, the goal of therapy is
      reperfusion of the ischemic area with thrombolytic therapy. Blood pressure (BP)
      goals during the first 24 hours depend on eligibility for tissue plasminogen
      activator (tPA). Following the acute phase, therapy is directed at prevention of
      recurrent stroke with antithrombotics and control of ischemic-stroke risk
      factors. This is a case of a 79-year-old female with newly diagnosed atrial
      fibrillation who was inappropriately started on aspirin for anticoagulation
      despite her high risk for stroke. She subsequently suffered a cardioembolic
      stroke. The patient was not a candidate for tPA because of the inability to
      determine when symptom onset occurred. Supportive care focused on BP and glycemic
      control as well as venous thromboembolism prophylaxis. Secondary prevention of
      stroke for this patient included treatment of hypertension, diabetes, and
      hypercholesterolemia as well as initiation of warfarin.

PMID- 20156004
TI  - Alternative ways to resolve contract disputes: implications for pharmacists,
      facilities, and patients.
AB  - Alternative dispute resolution (ADR) has been developed as an alternative to
      going to court to resolve disputes. Arbitration and mediation are the two most
      common forms, with arbitration involving a neutral third party who decides the
      controversy, the award being either binding or nonbinding on the parties base d
      on prior agreement. Mediation also involves a neutral third party, but the
      decision comes from the parties themselves reaching an agreement, with the
      mediator focused more on the process of securing a meeting of the minds. With the
      growing prevalence of ADR, pharmacists may encounter provisions in contracts-in
      either professional or personal life-so it is important that they understand the
      implications of such provisos. Pharmacists who serve patients in long-term care
      facilities also should be aware of the increasing use of provisions in patients'
      contracts with the institution and know how courts view those agreements. ADR is
      being encountered with increasing frequency, and by being familiar with the two
      most common approaches, pharmacists can keep abreast of developments and work to
      avoid pitfalls while adopting these approaches to resolve disputes in appropriate
      circumstances.

PMID- 20156005
TI  - Worker impairment: issues beyond alcohol or drugs.
AB  - PROBLEM: One of my older colleague's work is steadily declining, and sometimes
      her judgment seems "off," and she is easily distracted. Alcohol and drugs are
      most certainly not the problem nor is this a disability that is protected by the
      Americans with Disabilities Act, requiring accommodation. I want to help, but I'm
      not sure what to do. Any suggestions? SOLUTION: Deteriorating performance often
      is associated with difficulty with perception, memory, task perseverance, and
      reasoning skills-in other words, cognitive impairment. It's observant of you to
      note that alcohol/drugs are not an issue. Most people associate declining
      performance with alcohol or drug abuse for good reason; more often than not,
      employee assistance programs (EAPs) find alcoholism and drug abuse when employees
      are referred to them, and in fact, EAPs were initially developed with alcohol
      related problems in mind. EAPs now offer help in many more situations, including
      situations like this.

PMID- 20156007
TI  - Setting occupational exposure limits for unstudied pharmaceutical intermediates
      using an in vitro parallelogram approach.
AB  - Occupational exposure limits for unstudied pharmaceutical synthetic intermediates
      are often established under the assumption that penultimate and near-ultimate
      intermediates have the same structure-activity and dose-response as the ultimate
      active pharmaceutical ingredient (API). This is seldom the case because moieties
      that render biological activity to the API are often protected or modified for
      synthetic purposes. Incorrectly assuming that intermediates have biological
      activity similar to the API may lead to excessive exposure controls that in turn
      impose unnecessary ergonomic hazards on workers and greatly reduces the scale and
      efficiency of production. Instead of assuming intermediates have the same
      toxicity profile as the API, it is feasible to use a parallelogram approach to
      establish exposure limits for synthetic intermediates using low-cost in vitro
      data. By comparing in vitro responses of intermediates to structurally similar
      data-rich molecules such as the API, occupational exposure categories can be
      established for unstudied intermediates. In this contribution (1) methods for
      setting occupational exposure limits for data-poor compounds are reviewed; (2)
      applications and limitations of in vitro assays are discussed; (3) two exposure
      categorization examples are presented that rely on an in vitro parallelogram
      approach; and (4) inherent safeguards for uncertainties in pharmaceutical risk
      assessment are identified. In vitro hazard and dose-response information for
      unstudied intermediates that are structurally similar to well-studied APIs can
      greatly enhance the basis for setting occupational exposure limits for unstudied
      synthetic intermediates.

PMID- 20156008
TI  - A template for defining the perinatal care of monochorionic twins: the Istanbul
      international ad hoc committee.
AB  - This template was produced by the Working Group on Multiple Pregnancy and was
      endorsed by the International Board of the World Association of Perinatal
      Medicine. The purpose of this document is to expand the 2007 Istanbul
      international consensus statement on the perinatal care of multiple pregnancy and
      to focus on the care of monochorionic (MC) twins. The document represents the
      view and opinion of individuals who composed this ad hoc committee and discusses
      various aspects that are specific and relevant to the care of MC twin gestations.

PMID- 20156009
TI  - Guidelines for the management of postterm pregnancy.
AB  - A pregnancy reaching 42 completed weeks (294 days) is defined as postterm (PT).
      The use of ultrasound in early pregnancy for precise dating significantly reduces
      the number of PT pregnancies compared to dating based on the last menstrual
      period. Although the fetal, maternal and neonatal risks increase beyond 41 weeks,
      there is no conclusive evidence that prolongation of pregnancy, per se, is the
      major risk factor. Other specific risk factors for adverse outcomes have been
      identified, the most important of which are restricted fetal growth and fetal
      malformations. In order to prevent PT and associated complications routine
      induction before 42 weeks has been proposed. There is no conclusive evidence that
      this policy improves fetal, maternal and neonatal outcomes as compared to
      expectant management. It is also unclear if the rate of cesarean sections is
      different between the two management strategies. After careful identification and
      exclusion of specific risks, it would seem appropriate to let women make an
      informed decision about which management they wish to undertake. There is
      consensus that the number of inductions necessary to possibly avoid one
      stillbirth is very high. If induction is preferred, procedures for cervical
      ripening should be used, especially in nulliparous women. Close intrapartum fetal
      surveillance should be offered, irrespective of whether labor was induced or not.

PMID- 20156010
TI  - Periorbital contour abnormalities: hollow eye ring management with
      hyalurostructure.
AB  - PURPOSE: A new technique for treating "periorbital hollowing" with hyaluronic gel
      filling using a unique cannula designed specifically for periorbital use. METHOD:
      The study was conducted from December 2008 to July 2009. All the patients
      presenting to the Alcazar aesthetic and Orbital clinic for periorbital contour
      abnormality complains where included. A total of 26 patients (52 injections) in
      both functional and aesthetic categories were identified. The inclusion criteria
      where contour abnormalities in the periorbital area. These included contour
      abnormalities of the periorbital and brow region that presented clinically as:
      "hollow eye ring" and "hollow cavities" and "deflated eyebrow". The aim was to
      evaluate a new technique with a cannula specific for periorbital injections. This
      was designed in consultation with the author and was manufactured by the Thiebaud
      Company. Treatments where performed using local anaesthesia (emla 5% and an
      injection of 1% Xylocaine adrenalised to 32-gauge needle) using the same protocol
      as Coleman lipostructure but using hyaluronic acid gel. The hyaluronic acid gel
      used in each case was Restylane (Q-Med-Sweden). Follow-up was over 6 months and
      performed photographically and with a patient self-evaluation questionnaire. The
      clinical postoperative assessment examined for bruising or swelling
      postinjection. The rates of complication were compared to published results and
      the authors own series before switching to the new cannula. RESULTS: After
      analysis of the patient responses 24 patients (92%) with a 6 months' follow-up
      were satisfied or very satisfied of aesthetic result after hyalurostructure of
      periorbital region. The use of the specially designed cannula led to less
      complication. There were 3 cases of bruising (3/52) and 4 cases of lymphatic
      stasis (4/52). We also noted fewer surface irregularities and a better
      distribution of the product as the injection was a retro orbicular pre periosteal
      plane). CONCLUSION: Treatment of the periorbital region and tear trough by
      hyaluronic acid injection has been described previously. But often the risks of
      this delicate anatomic region and bruises caused by needles followed by the
      appearance of hollow eye ring due to deposition of haemosiderin have limited the
      development of this technique. We propose a new treatment for hollow eye rings
      and for peri orbital region adapted from Lipostructure but with hyaluronic acid
      and facilitating treatment protocol of that region with improved aesthetic
      results: hyalurostructure.

PMID- 20156012
TI  - Systems technology in the operating theatre: a prerequisite for the use of
      advanced devices in surgery.
AB  - The development of endoscopic techniques has significantly changed surgery. The
      increasing complexity of devices being used has increased the demand for improved
      ergonomics and functionality. Since the early 1990s the development of system
      solutions for the operating room (OR) has been a topic of major interest for
      surgeons and industry. The first integrated surgical workplace system was
      introduced by Dornier (Orest) in 1994. Several other solutions are now
      commercially available. Their common feature is the ability to control the
      different functions of the individual devices (e.g. high-frequency waves, camera,
      or insufflation) via remote control systems directly from the operating table.
      Other developments in OR systems include ergonomic aids for the surgeon, such as
      a chair dedicated to the functional needs of endoscopic surgery. The chair is
      powered by electric motors controlled by a foot-pedal joystick and its position
      can be altered to achieve the desired position in the OR. Also significant in
      endoscopic surgery was the introduction of robotic technology, namely devices
      that assist solo-surgery and manipulators for microsurgical instrumentation.

PMID- 20156013
TI  - A voice-controlled network for universal control of devices in the OR.
AB  - To achieve the benefits of an Intelligent Operating Room (OR), we envision an OR
      control center--a voice-controlled network of medical devices. This central
      controller allows doctors and nurses to control many smart devices in a minimally
      invasive OR, in the same way the operating system of a personal computer allows
      users to control computer peripherals, such as a printer or modem. Surgeons in
      the OR may use voice commands to control surgical devices when their hands are
      busy. In addition, the OR staff may use a touch-sensitive display panel to
      control any device in the OR from a single, convenient location. As an example,
      this paper describes a new 'operating system for the OR', called HERMES. Because
      of the unique demands of the Intelligent OR, the design of such a voice-control
      network involves several challenges: safety, reliability and ease of use. This
      paper discusses the design strategies for the HERMES control network and presents
      findings from the use of commercial HERMES in operating rooms.

PMID- 20156014
TI  - Systems workplace for endoscopic surgery.
AB  - With the advent of minimally invasive surgery (MIS) a decade ago, the
      requirements for operating rooms (OR) and their equipment have been increased.
      Compared with conventional open surgery, the new endoscopic techniques require
      additional tools. Television systems, for video-assisted image acquisition and
      visualisation, including cameras, monitors and light systems, as well as
      insufflators, pumps, high-frequency units, lasers and motorised therapy units,
      are nowadays usually made available on carts during endoscopic surgery. In
      conjunction with a set of endoscopic instruments, these high-tech units allow new
      operating techniques to be performed. The benefit for patients has become clear
      in recent years; however, the technical complexity of OR has also increased
      considerably. To minimise this problem for the OR personnel, the MIS concept
      'OR1' (Operating Room 1) was developed and implemented. OR1 is a fully functional
      and integrated multi-speciality surgical suite for MIS. The centrepieces of the
      OR1 are the Storz Communication Bus (SCB) and the advanced image and data
      archiving system (Aida) from Karl Storz, Tuttlingen, Germany. Both components
      allow monitoring, access and networking of the MIS equipment and other OR
      facilities, as well as the acquisition, storage and display of image, patient and
      equipment data during the endoscopic procedure. A central user interface allows
      efficient, simplified operation and online clinical images. Due to the system
      integration, the handling of complex equipment is considerably simplified,
      logistical procedures in the OR are improved, procedure times are shorter and,
      particularly noteworthy, operative risk can be reduced through simplified device
      operation.

PMID- 20156015
TI  - System solutions for the integration of devices in the OR.
AB  - The technical complexity of the surgical arena, as well as of related specialised
      fields, has increased significantly. A look at the current situation in various
      surgical disciplines shows that, despite existing high-tech equipment, the
      operating room (OR) can still not be considered an ergonomic and optimised work
      environment. Industrial suppliers have integrated new procedures and techniques
      into surgical disciplines, often without consulting other manufacturers and
      without establishing or implementing appropriate standards. This paper describes
      the development of an integrated workstation for the OR and its related technical
      and clinical aspects, e.g. process analysis, system integration, standardisation,
      image processing, user interfaces, communication protocols (CANopen, DICOM) and
      networking. The first introduction of the prototype to our clinical partners has
      confirmed that the implementation of an optimised system workstation in the OR
      results in improved processes. The standardised and simplified user guidance
      leads to improved ergonomy. The selected communication standard between the
      subsystems of the diverse industrial suppliers gives the user more flexibility in
      configuring the individual OR system. Intensive collaboration between industry
      and clinical partners will continue to be vital for the further development of
      such complex system workstations in medicine.

PMID- 20156016
TI  - Notes from the industry: new solution for the integration of the computer
      tomograph into the OR environment.
AB  - Seconds can be crucial in surgery. Maquet AG in Germany has developed a new
      integrated surgical work-station for faster, safer and more gentle therapeutic
      procedures. Awigs, the advanced workplace for image-guided surgery, is a unique
      unit that integrates diagnostics, surgery and patient-monitoring without the risk
      of moving the patient from their bed.

PMID- 20156017
TI  - Experience with a new OR dedicated to robotic surgery.
AB  - The use of robotic technology for minimally-invasive cardiac surgery requires a
      new operating room (OR) environment. Remote surgery is performed by isolating the
      surgeon in a central control-room, while the surgical manipulator is located in
      the OR. Due to the complex nature of these new procedures and the limited access
      that, unlike in open cardiac surgery, no longer allows direct visualisation of
      the heart, extensive intra-operative monitoring is essential. The OR features an
      angiography unit that allows multidisciplinary procedures to be carried out in
      close collaboration with interventional cardiologists.

PMID- 20156018
TI  - Robotics and telecommunication systems to provide better access to ultrasound
      expertise in the OR.
AB  - Surgery has begun to evolve as a result of the intense use of technological
      innovations. The result of this is better services for patients and enormous
      opportunities for the producers of biomedical instruments. The surgeon and the
      technologist are fast becoming allies in applying the latest developments of
      robotics, image treatment, simulation, sensors and telecommunications to surgery,
      in particular to the emerging field of minimally-invasive surgery.
      Ultrasonography is at present utilised both for diagnostic and therapeutic
      purposes in various fields. Intraoperative US examination can be of primary
      importance, especially when dealing with space-occupying lesions. The widening
      use of minimally-invasive surgery has furthered the development of US for use
      during this type of surgery. The success of a US examination requires not only a
      correct execution of the procedure, but also a correct interpretation of the
      images. We describe two projects that combine robotics and telecommunication
      systems to provide better access to US expertise in the operating room. The
      Midstep project has as its object the realisation of two robotic arms, one for
      the distant control of the US probe during laparoscopic surgery and the second to
      perform tele-interventional US. The second project, part of the Strategic CNR
      Project-'Robotics in Surgery', involves the realisation of a common platform for
      tracking and targeting surgical instruments in video-assisted surgery.

PMID- 20156019
TI  - Image recognition and neuronal networks: intelligent systems for the improvement
      of imaging information.
AB  - Intelligent computerised systems can provide useful assistance to the physician
      in the rapid identification of tissue abnormalities and accurate diagnosis in
      real-time. This paper reviews basic issues in medical imaging and neural network
      based systems for medical image interpretation. In the framework of intelligent
      systems, a simple scheme that has been implemented is presented as an example of
      the use of intelligent systems to discriminate between normal and cancerous
      regions in colonoscopic images. Preliminary results indicate that this scheme is
      capable of high accuracy detection of abnormalities within the image. It can also
      be successfully applied to different types of images, to detect abnormalities
      that belong to different cancer types.

PMID- 20156020
TI  - Endosupralayngeal laser resection of a symptomatic anatomical laryngeal variant:
      a minimally-invasive technique for a newly-recognised condition.
AB  - A variant of thyroid cartilage anatomy has recently been described as a cause of
      significant pharyngeal and laryngeal symptoms. After clinical recognition, spiral
      CT imaging confirms the anatomical relationships and a minimally-invasive
      technique is offered to allow surgical removal of the variant. The authors
      describe the surgical technique that was developed to avoid the need for an
      alternative, more conventional, external approach, and the instruments found to
      be particularly suitable for providing appropriate access to the supralaryngeal
      region.

PMID- 20156021
TI  - An overview of superelastic stent design.
AB  - The purpose of this paper is to contrast the performance of self-expanding and
      balloon-expandable stents. While both approaches to stenting have proven to be
      successful in treating a wide range of vascular disease, there are significant
      differences in the philosophy behind and properties of the two types of stents.
      Many of these differences, such as strength, stiffness (or compliance), recoil,
      dynamic scaffolding, vessel conformity and fatigue resistance will be highlighted
      by studying the mechanics of the stent alone, and then of a stent within a
      vessel. These differences can be summarised by observing that self-expanding
      stents provide more anatomically-correct scaffolding, while balloon-expandable
      stents provide rigid and uncompromising reinforcement. Other differences, such as
      corrosion resistance, placement accuracy and visibility, will also be briefly
      summarised.

PMID- 20156022
TI  - The use of shock waves in medicine--a tool of the modern OR: an overview of basic
      physical principles, history and research.
AB  - Extracorporeal-generated shock waves were first used in medical therapy, to
      disintegrate kidney stones, approximately 20 years ago. Since this time, shock
      waves have changed the treatment of urolithiasis substantially and are now the
      first-choice treatment for kidney and ureteral stones. First clinical
      investigations of the shock-wave treatment of Induratio Penis Plastica (IPP) are
      showing promising results. Shock waves have also been used in orthopaedics and
      traumatology, to treat insertion tendinitis, non-unions or delayed unions,
      avascular necrosis of the head of femur and other necrotic bone alterations.
      Shock-wave application has also been used in the treatment of horse tendons,
      ligaments and bones in veterinary medicine. The theory of shock-wave therapy for
      orthopaedic diseases involves the stimulation of healing processes in tendons,
      surrounding tissue and bones. This is a completely different approach from that
      of urology, where shock waves are used for disintegration. This paper gives an
      overview of the basic physical principles of shock waves, and the history and
      basic research behind shock-wave use in medicine.

PMID- 20156023
TI  - The medical engineering program of Forschungszentrum Karlsruhe.
AB  - The research activities of the Forschungszentrum Karlsruhe on minimally-invasive
      surgery (MIS) have for several years improved techniques and instrumentation for
      different types of MIS. Many types of instruments and robotic devices have been
      developed and new techniques implemented. In this paper we present the most
      recent results from our different projects, such as endoscopic heart surgery,
      tracking systems, a camera guidance device, telemanipulator systems, minimally
      invasive breast biopsy in closed-bore MRI, endoscopic training simulators and
      developments using smart materials (e.g. Nitinol).

PMID- 20156024
TI  - Anatomical analysis and preoperative planning of correctional osteotomies:
      slipped capital femoral epiphysis (SCFE).
AB  - SCFE is defined as the slippage of the femoral head relative to the femoral neck
      along the proximal femoral growth plate. The femoral head shifts and rotates
      along the proximal end of the femoral neck, usually posteriorly and interiorly.
      The pathoanatomical findings are characterised by the changed relationship
      between the femoral head and femoral metaphysis, and between the femoral head and
      the acetabulum. A reduced femoral anteversion, a varus deformity of the femur, a
      shortening of the femoral metaphysis and an anterior metaphyseal prominence are
      also regularly observed. This may lead to impingement between the femoral
      metaphysis and the acetabular rim. Potential consequences of this complex 3D
      deformity are pain, a reduced range of hip motion and an early degenerative joint
      disease. In moderate and severe cases a redirectional femoral osteotomy is
      recommended. Different techniques, such as subcapital, base-of-neck,
      intertrochanteric and subtrochanteric osteotomies, have been described. These
      correctional osteotomies aim towards a reconstruction of the hip joint geometry,
      to prevent early arthritic degeneration. Currently, the planning of surgical
      treatment in these cases is based on measurements on antero-posterior and lateral
      plain radiographs. The relevant angle for planning of correctional osteotomies is
      the physis-shaft angle, determined in both plains. These angles describe the
      degree of slippage, thereby helping the surgeon to indicate and plan a
      correctional osteotomy. However, plain radiographs are projectional images and
      therefore carry inaccuracies caused by the overlay of anatomical structures and
      an incorrect positioning of the patient. 3D reconstructions are more accurate and
      provide substantial additional information for the surgeon, such as, for example,
      the anteversion of the acetabulum. We have developed interactive 3D software to
      measure projected angles, to analyse the geometry of the proximal femur and to
      determine the orientation of the acetabulum based on 3D reconstructions of CT
      data-sets. A program was also developed to simulate different techniques of
      osteotomies and to evaluate the postoperative range of hip motion and the hip
      joint geometry. Accurate 3D measurements, additional anatomical information,
      simulations of different techniques of osteotomies and the evaluation of
      simulated postoperative results enables the surgeon to determine the best
      surgical treatment, based on the clinical findings.

PMID- 20156025
TI  - Image-guided therapy and intraoperative MRI in neurosurgery.
AB  - Computer-assisted 3D planning, navigation and the possibilities offered by intra
      operative imaging updates have made a large impact on neurological surgery. Three
      dimensional rendering of complex medical image information, as well as co
      registration of multimodal sources has reached a highly sophisticated level. When
      introduced into surgical navigation however, this pre-operative data is unable to
      account for intra-operative changes, ('brain-shift'). To update structural
      information during surgery, an open-configured, intra-operative MRI (Signa SP,
      0.5 T) was realised at our institution in 1995. The design, advantages,
      limitations and current applications of this system are discussed, with emphasis
      on the integration of imaging into procedures. We also introduce our integrated
      platform for intra-operative visualisation and navigation, the 3D Slicer.

PMID- 20156026
TI  - Aortic and venous valve for percutaneous insertion.
AB  - The purpose of this paper is to present in vitro and in vivo experimental
      evaluation of a new, artificial, bicuspid, aortic and venous valve. Valves were
      constructed from square stents with barbs covered by porcine small intestine
      submucosa (SIS). A valve 15 mm in diameter was tested in a flow model (2.5 l/min)
      with pressure measurement. A 100-ml rubber bag attached to a side arm of the flow
      model simulated heart ejection fraction. In acute (n=6) and short-term (n=3)
      experiments conducted in four swine and four dogs, valves ranging from 16-28 mm
      in diameter were placed into the ascending aorta through 10 F sheaths; three were
      placed subcoronary and six in a supracoronary position. Function and stability of
      the valves were studied with pressure measurements and aortograms. Three short
      term animals were sacrificed for gross and histologic evaluation at one, two and
      four weeks respectively. In an acute experiment, venous valves with four barbs
      were placed into the IVC through an 8 F guiding catheter in three dogs. For
      longer-term testing, valves were placed into the IVCs and iliac veins of three
      young swine. The animals were followed up after two weeks with venograms, then
      were sacrificed for gross and histologic evaluation.

PMID- 20156029
TI  - On the analysis of BIS stage epochs via fuzzy clustering.
AB  - Among various types of clustering methods, partition-based methods such as k
      means and FCM are widely used in the analysis of such data. However, when
      duration between stimuli is different, such methods are not able to provide
      satisfactory results because they find equal size clusters according to the
      fundamental running principle of these methods. In such cases, neighborhood-based
      clustering methods can give more satisfactory results because measurement series
      are separated from one another according to dramatic breaking points. In recent
      years, bispectral index (BIS) monitoring, which is used for monitoring the level
      of anesthesia, has been used in sleep studies. Sleep stages are classically
      scored according to the Rechtschaffen and Kales (R&K) scoring system. BIS has
      been shown to have a strong correlation with the R&K scoring system. In this
      study, fuzzy neighborhood/density-based spatial clustering of applications with
      noise (FN-DBSCAN) that combines speed of the DBSCAN algorithm and robustness of
      the NRFJP algorithm is applied to BIS measurement series. As a result of
      experiments, we can conclude that, by using BIS data, the FN-DBSCAN method
      estimates sleep stages better than the fuzzy c-means method.

PMID- 20156030
TI  - Immunomodulatory effects of antifungal agents on the response of human monocytic
      cells to Aspergillus fumigatus conidia.
AB  - We evaluated the immunomodulatory effects of three different classes of
      antifungal agents on the human monocytic cell line, THP-1, which had been
      stimulated in vitro with Aspergillus fumigatus conidia. Cells treated with
      amphotericin B (AmB), micafungin (MF), and voriconazole (VCZ), at concentrations
      not affecting cell viability, reduced production of tumor necrosis factor (TNF)
      alpha in response to conidia, with the greatest reduction noted with VCZ. The
      reduction of TNF-alpha production correlated with TNF-alpha gene expression
      assessed by PCR and nuclear factor kappaB (NF kappaB) levels. Co-stimulation with
      granulocyte-macrophage colony stimulating factor abolished immunomodulatory
      effects of the drugs. Antifungal agents affect the immune reaction caused by A.
      fumigatus conidia in stimulated monocytes at clinically relevant drug
      concentrations. Because drugs with different mechanisms of action produced this
      effect, this suggests that it is the result of factors mediated by the cells. The
      impact of these immunomodulatory effects needs assessment.

PMID- 20156031
TI  - Influence of the chitosan nature on the transfection efficacy of DNA-loaded
      nanoparticles after hydrodynamic administration in mice.
AB  - A commercially available chitosan with a degree of deacetylation (DD) of 85% and
      a molecular weight (Mw) of 400 kDa was modified by acetylation with acetic
      anhydride to obtain a chitosan with a DD of 75%. Both polysaccharides were used
      to prepare DNA-chitosan nanoparticles by charge interactions with pDNA
      (coacervation process). Both resulting nanoparticles showed an almost total DNA
      loading efficiency (96%) and displayed similar physico-chemical properties with a
      size of approximately 200 nm and a zeta potential close to +20 mV. In order to
      study the effect of the DD on the properties of DNA-chitosan nanoparticles as
      gene delivery systems, the hydrodynamics-based procedure was used. The transgene
      expression was observed using either the green fluorescent protein (GFP) or the
      luciferase (Luc) as reporter genes. After the hydrodynamic injection, the DNA
      chitosan nanoparticles were accumulated in the liver, where the transgene
      expression was mostly localized. Interestingly, the decrease of the DD affected
      the transgene expression, improving the initial burst effect and accelerating the
      DNA release. Both combined effects led to an increase in the transgene expression
      levels. In addition, the emitted bioluminescence could be detected over 105 days
      for all the formulations injected. The calculation of the kinetic parameters
      (C(max), AUC, Ke, t(1/2) Ke and MET) gave some interesting information regarding
      the abilities to control the DNA release of the two DNA-chitosan formulations
      tested and allowed narrower comparisons.

PMID- 20156032
TI  - Long-term up to 24-month efficacy and safety of concomitant prescription omega-3
      acid ethyl esters and simvastatin in hypertriglyceridemic patients.
AB  - OBJECTIVE: Assess the long-term efficacy and safety of prescription omega-3-acid
      ethyl esters (P-OM3) coadministered with simvastatin in an extension of the
      Combination of Prescription Omega-3 Plus Simvastatin (COMBOS) trial. METHODS:
      COMBOS included hypertriglyceridemic patients (triglyceride [TG] >or=200 mg/dL
      and <500 mg/dL or >or=2.26 mmol/L and <5.64 mmol/L) with low density lipoprotein
      cholesterol (LDL-C) level no greater than 10% above the National Cholesterol
      Education Program, Adult Treatment Panel III treatment goal. After an 8-week lead
      in phase with simvastatin 40 mg/day (which continued throughout the trial),
      subjects were randomized to 8 weeks of P-OM3 4 g/day or placebo. Completers were
      eligible to participate in a 24-month extension study. Those who received placebo
      + simvastatin in COMBOS switched to open-label P-OM3 + simvastatin ('Switchers');
      those who received P-OM3 + simvastatin during COMBOS continued the same regimen
      (open-label) in the extension phase ('Non-switchers'). The primary endpoint was
      the difference between Non-switchers and Switchers in median percent change in
      non-high-density lipoprotein-cholesterol (non-HDL-C) from COMBOS end of treatment
      to Month 4 of the extension phase. RESULTS: At Month 4 from COMBOS end of
      treatment, non-HDL-C was reduced by a median of 9.4% in Switchers and increased
      by 0.9% in Non-switchers (p < 0.001). For the total population (combined Non
      switcher + Switcher population), the median percent change from COMBOS baseline
      to Months 4, 12, and 24 was -8.3%, -7.3%, and -8.9%, respectively (all p <
      0.001). This extension study revealed no unexpected safety findings. A limitation
      of this study was a gap between completion of COMBOS and enrollment in the
      extension phase for some patients; however, a post-hoc non-HDL-C sensitivity
      analysis performed at the 4-month primary endpoint revealed no influence of gap
      on study results. CONCLUSIONS: In this 24-month extension study, P-OM3 was
      generally well tolerated, and produced sustained reductions in non-HDL-C levels
      in simvastatin-treated patients with TG levels between 200 and 500 mg/dL (2.26
      mmol/L and 5.64 mmol/L). CLINICAL TRIAL REGISTRY NUMBER: NCT00903409.

PMID- 20156033
TI  - Botulinum toxin may predict the outcome of endoscopic sphincterotomy in episodic
      functional post-cholecystectomy biliary pain.
AB  - OBJECTIVE: A retrospective clinical audit was carried out to identify whether
      relaxation of the sphincter of Oddi (SO) by botulinum toxin (BTX) injection can
      select patients with episodic functional post-cholecystectomy biliary pain who
      will benefit from endoscopic sphincterotomy. PATIENTS AND METHODS: Sixty-four
      patients complaining of functional post-cholecystectomy biliary pain with a
      frequency of at least four episodes per month had 100 units of BTX injected into
      their SO muscle in four aliquots. After review patients with a pain free interval
      following BTX injection of at least 4 weeks were offered biliary endoscopic
      sphincterotomy and their outcome assessed. RESULTS: Of the 64 patients 46 (72%)
      had at least four pain free weeks after BTX therapy and 44 of these 46 patients
      (96%) went on to experience pain relief following endoscopic sphincterotomy. Of
      the 64 patients 41 had sphincter of Oddi manometry prior to BTX injection. Every
      patient with sphincter of Oddi hypertension defined by manometry and at least 4
      weeks' pain relief following BTX (24) had pain relief following sphincterotomy.
      Fifteen (94%) of the 16 patients who did not undergo manometry but reported at
      least 4 weeks' pain relief after BTX had pain relief after sphincterotomy.
      CONCLUSION: Botulinum toxin relaxation of the SO may be a useful method of
      predicting the symptom response to endoscopic sphincterotomy in patients who have
      episodic functional biliary pain.

PMID- 20156034
TI  - Accuracy of oscillometric devices in children and adults.
AB  - Clinical validation of blood pressure oscillometric devices are almost
      exclusively conducted in adults. Because oscillometric devices are used in
      children, it is critical to assess their accuracy also in this population. We
      compared blood pressure readings using an oscillometric automated device (Dinamap
      XL, model CR9340) with readings obtained with the mercury auscultatory method in
      children and adults. Blood pressure was measured in 30 children (15 boys and 15
      girls; 9.5+/-1.0 years old) and their parents (25 mothers and 15 fathers; 41.0+/
      5.0 years old). In children, mean difference (+/-SD) in systolic blood pressure
      (DeltaBP) readings (oscillometric-auscultatory) was +0.6+/-4.7 mmHg (range: -10
      to +11); mean diastolic DeltaBP was 21.3+/-7.5 mmHg (range: -18 to +19) and
      decreased with increasing diastolic BP. In adults, mean systolic DeltaBP was
      +0.4+/-5.2 mmHg (range: -12 to +15) and mean diastolic DeltaBP was -5.2+/-6.0
      mmHg (range: -25 to +8) (p<0.001). While the device was not accurate enough to be
      recommended, our study also shows that the accuracy of blood pressure
      oscillometric devices can differ between children and adults. Clinical accuracy
      of oscillometric devices should be tested in the specific populations in whom
      blood pressure is measured.

PMID- 20156035
TI  - The influence of cigarette and qalyan (hookah) smoking on serum nitric oxide
      metabolite concentration.
AB  - OBJECTIVE: To assess the effect of exposure to cigarette and qalyan (hookah)
      smoking on serum nitric oxide (NO) metabolites (NO(x)) concentration. MATERIAL
      AND METHODS: Fasting serum NO(x) was measured by the Griess method in 333 men
      free of diabetes, hypertension and cardiovascular disease selected from
      participants of the Tehran Lipid and Glucose Study. Subjects were classified into
      active and passive cigarette smokers and they were age-matched with the non
      smoker groups (n = 93/group). Twenty-seven qalyan smokers were also included in
      the study with their age-matched controls. RESULTS: Multivariable-adjustment
      serum NO(x) values were compared between groups by analysis of covariance. Serum
      NO(x) was significantly higher (p < 0.05) in the active smokers [28.9 micromol/L
      (95% CI 26.2-32.0)] compared to nonsmokers [24.1 micromol/L (95% CI 21.8-26.7)].
      A positive correlation was found between serum NO(x) and the number of cigarettes
      smoked per day (r = 0.222, p < 0.05). Qalyan smokers had higher serum NO(x)
      levels compared to the non-smoker controls [34.3 micromol/L (95% CI 27.8-42.3)
      vs. 22.5 micromol/L (95% CI 18.4-27.6), p < 0.01]. CONCLUSION: Active cigarette
      and qalyan smoking are associated with high serum NO(x) levels.

PMID- 20156036
TI  - In vitro inhibition of low density lipoprotein carbamylation by vitamins, as an
      ameliorating atherosclerotic risk in uremic patients.
AB  - INTRODUCTION: Previous studies have shown that the increase of carbamylated LDL
      (cLDL), a product of nonenzymatic modification of LDL in human serum by urea
      derived cyanate, may cause cardiovascular complications in patients with chronic
      renal insufficiency. This study examined the inhibitory effect of ascorbic acid,
      alpha-tocopherol and lycopene on LDL carbamylation in an in vitro model system.
      METHODS: After isolation of LDL from plasma using an ultracentrifuge technique,
      cyanate was added to it and then LDL carbamylation was measured in both the
      absence and presence of ascorbic acid, alpha-tocopherol and/or lycopene by the
      colorimetric method at 530 nm. RESULTS: The findings indicated that these
      vitamins inhibit LDL carbamylation and the most effective vitamin of the three is
      lycopene. Moreover, the effect of lycopene on this process increased in the
      presence of ascorbic acid and alpha-tocopherol. CONCLUSION: This study indicated
      that ascorbic acid, alpha-tocopherol and lycopene with antioxidant activity can
      probably inhibit LDL carbamylation and therefore may have a role in ameliorating
      atherosclerotic risk of patients with kidney failure. However in vitro and in
      vivo investigations are required to confirm the exact effects of these vitamins
      on patients suffering from uremic disorders.

PMID- 20156041
TI  - 'Belonging'. 'Patients' experiences of social relationships during pulmonary
      rehabilitation.
AB  - AIM: To unpack and interpret descriptions of experiences of social relationships
      during pulmonary rehabilitation (PR) for people living with chronic obstructive
      pulmonary disease (COPD). METHOD: Inspired by interpretive phenomenology,
      individual qualitative interviews were conducted twice with 18 persons from COPD
      rehabilitation units in two general hospitals. Qualitative content analysis was
      performed. RESULTS: Analysis of the interviews revealed the overarching theme of
      belonging. The participants emphasised social integration in rehabilitation
      groups as well as support from peers and health-care personnel as important
      dimensions of social relationships with regard to PR. Active participation in and
      engagement with the groups provided opportunities for patients to share their
      knowledge, encouraged mutual trust, and support and increased self-confidence,
      and motivation for self-care and further social participation. Integration in the
      groups and perceived support during PR made coping and adaptation easier and had
      a positive effect on quality of life. CONCLUSIONS: Patients' perspectives on PR
      were strongly influenced by certain facets of social relationships, such as
      social integration and social support. Patients', peers' and health-care
      professionals' strategies to promote social support and social integration should
      be further explored in the future, both in different contexts and for longer
      periods of time.

PMID- 20156042
TI  - A review of simple, non-invasive means of assessing peripheral arterial disease
      and implications for medical management.
AB  - Abstract Atherosclerotic peripheral arterial disease (PAD) is highly prevalent in
      the elderly and subjects with atherosclerotic risk factors such as smoking,
      diabetes mellitus, hypertension, and hyperlipidemia. Importantly, PAD is rarely
      an isolated condition, but rather a manifestation of systemic atherosclerosis.
      Hence, there is often coexisting disease in the coronary and cerebral arteries
      and, consequently, an increased risk of myocardial infarction and stroke.
      Intermittent claudication is the classic symptom of PAD, yet up to 50% of
      patients are asymptomatic. Despite the availability of reliable, non-invasive
      screening tests, PAD is largely underdiagnosed and undertreated, mostly due to
      the paucity of symptoms and underutilization of screening tools. The ankle
      brachial index (ABI), a simple, rapid, and inexpensive diagnostic tool, holds
      much prognostic value for PAD diagnosis and is ideal for implementation in the
      primary care physician's office. The early detection of PAD with ABI screening
      and subsequent medical management represents a critical opportunity to prevent
      considerable vascular morbidity and mortality. The management of PAD must address
      claudication symptoms (with cilostazol or pentoxifylline, or in severe cases
      endovascular or surgical revascularization) and modifiable atherosclerotic risk
      factors (with an aggressive global risk-reduction regimen involving lifestyle
      modifications, exercise, smoking cessation, and antiplatelet, lipid-lowering, and
      antihypertensive therapy).

PMID- 20156043
TI  - Scavenger receptor class BI mediates the anti-apoptotic effect of erythropoietin.
AB  - A scavenger receptor of the B class (SR-BI)/human homolog of SR-BI, CD36, and
      LIMP II analogous-1 (CLA-1), has been identified as a receptor for high-density
      lipoprotein (HDL). Mice lacking SR-B1 develop anemia, plausibly explained by the
      observation that the erythrocyte life-span in these animals is reduced.
      Erythropoietin (EPO) is known to promote survival of erythroid cells, in large
      part through protection from apoptosis. We have examined the role of EPO on hSR
      BI/CLA-1 expression and erythrocyte apoptosis. Endogenous expression of hSR
      BI/CLA-1 was increased by exposure to EPO. EPO increased transcriptional activity
      of hSR-BI/CLA-1 promoter. The stimulatory effect of EPO on hSR-BI/CLA-1 promoter
      activity was abrogated by LY294002, specific inhibitor of phosphatidylinositol-3
      kinase (PI3K). Constitutively active Akt stimulates the activity of the hSR
      BI/CLA-1 promoter and a dominant-negative mutant of Akt abolished the ability of
      EPO to stimulate promoter activity. Finally, EPO in combination with HDL
      protected the cell from apoptosis, which suggests that hSR-BI/CLA-1 induced by
      EPO might contribute to the erythrocyte life-span.

PMID- 20156044
TI  - Penile rehabilitation therapy following radical prostatectomy.
AB  - PURPOSE: To compare erectile function (EF) recovery of patients treated by early
      penile rehabilitation therapy (PRT) with sildenafil and with control group.
      METHOD: Forty men treated by bilateral nerve sparing radical prostatectomy (NSRP)
      and with a normal pre-operative EF were enrolled. Fourteen days after surgery,
      they were randomised to a flexible-dose sildenafil group and to a control group.
      The International Index of Erectile Function (IIEF) questionnaire was completed
      before surgery and at 3, 6, 12 and 24 weeks after NSRP. RESULTS: In the group
      treated, the mean IIEF score before surgery was 26.2 and 14.1, 16.2, 22.5 and
      25.2 at 3, 6, 12 and 24 weeks after NSRP, respectively. In the control group, the
      respective scores were 26.5 and 12.4, 15.8, 15.3 and 17.4. There was a
      significant difference in IIEF mean score (25+/-6 vs. 17+/-9, p<0.05) and in the
      potency rate (87% vs. 56%) between the groups at 24 weeks after NSRP. The
      percentage of patients who were capable of having medication-unassisted
      intercourse was 54% vs. 21%; 34% vs. 18% of patients had a normal EF with 72% vs.
      32% of responders to sildenafil. CONCLUSIONS: PRT with PDE-5 inhibitors should be
      offered early after RP to allow the recovery of EF.

PMID- 20156045
TI  - The impact of bilateral therapy on upper limb function after chronic stroke: a
      systematic review.
AB  - PURPOSE: To determine the evidence for bilateral therapy interventions aimed at
      improving upper limb (UL) function in adults with a range of UL activity
      limitations due to a first time chronic stroke. METHOD: Seven databases were
      searched prior to 2008 for articles reporting experimental studies investigating
      bilateral UL interventions on functional outcome in participants with a first
      stroke, 6 or more months prior. Included articles were evaluated with the quality
      index, a tool which evaluates the quality of both randomised and non-randomised
      studies. Data relating to study design and functional outcome were extracted.
      RESULTS: Nine articles were included; three reported on randomised controlled
      trials (RCT) and six on cohort studies. Eight studies incorporated a mechanical
      device as their bilateral intervention. Bilateral arm training with rhythmic
      auditory cueing (BATRAC) was the most commonly used mechanically based
      intervention, and three of the four uncontrolled BATRAC studies reported
      significant improvements in UL function post-intervention, however these results
      were not substantiated by a RCT study of the BATRAC intervention. One study
      demonstrated significant functional improvements after 6 days of training with a
      non-mechanical bilateral task. Of the four studies that performed a follow-up
      assessment, three reported significant improvement in UL function. Quality index
      ratings of the included studies ranged from 18 to 25 out of 27. CONCLUSION: There
      is some evidence that bilateral therapy improves function in adults with chronic
      stroke, however more quality RCTs are required to strengthen this evidence.

PMID- 20156046
TI  - Evaluation and treatment of synkinesis with botulinum toxin following facial
      nerve palsy.
AB  - PURPOSE: To assess the effect and efficacy of botulinum toxin type A (BTX-A) in
      reducing synkinesis in aberrant facial nerve regeneration (following facial
      paralysis). METHOD: A total of 55 sessions of BTX-A (Botox) infiltration were
      performed on 30 patients (23 female) with synkinesis after facial palsy. Each
      subject was injected with 2.5 units of BTX-A in each injection site (the sites
      were chosen on a case-by-case basis). The synkinetic muscles targeted include:
      orbicularis oculi, zygomaticus major, depressor labii inferioris, platysma,
      healthy frontalis and healthy corrugator supercilii. The patients were examined
      using the Sunnybrook Facial Grading System, both before the BTX-A treatment and
      after an average of 35 days. RESULTS: All 30 patients experienced improvement to
      the synkinesis after treatment. Total scores: median pre-BTX-A: 40; post 53 p =
      0.004. Resting symmetry scores: mean pre-BTX-A -7.1; post: -3.5; median pre -5
      [interquartile range (IQR) -10 to -5]; post: -5 (IQR -5 to 0); p = 0.0001.
      Symmetry of voluntary movement median pre-BTX-A: 56 post 60 p = 0.10. Synkinesis
      scores: median pre-BTX-A: -9 post -3 p < 0.0001. Mean duration of improvement was
      4 months. CONCLUSIONS: BTX-A injection treatment was effective in reducing facial
      synkinesis, thus improving facial expression symmetry both at rest and in
      voluntary movements.

PMID- 20156047
TI  - Elderly persons' experience and management of eating situations 6 months after
      stroke.
AB  - PURPOSE: To explore the experience and management of eating situations among
      persons affected by stroke, 6 months after stroke onset. METHOD: A qualitative
      constant comparative approach, influenced by principles of grounded theory, was
      used to analyse the interviews. Thirteen participants were interviewed in the
      home setting 6 months after the stroke. RESULTS: Experiences and desire to master
      eating situations varied, and was related to values and previous habits. Eating
      difficulties were experienced as disgusting, uncomfortable, strenuous, or
      unproblematic and not implying shame. Getting help from others could be
      experienced as embarrassing and undesirable. In particular, eating could be more
      difficult when eating in company of unfamiliar people. The participants found new
      ways of mastering eating situations. Some had regained former routines.
      CONCLUSIONS: Old values and habits and/or involvement of other people were the
      basis of mastering eating situations. New ways of mastering were found, some
      accepted, and got used to the new situation. Some regained former routines. This
      knowledge could contribute to health care personnel's awareness of each patient's
      individual values and previous habits during the rehabilitation process. A
      dialogue is needed with the person suffering from eating difficulties after
      stroke, to help create the best possible individual conditions for mastering
      eating situations.

PMID- 20156048
TI  - Substance abuse and psychosocial adaptation to physical disability: analysis of
      the literature and future directions.
AB  - PURPOSE: To analyse the current state of the literature with respect to substance
      abuse and psychosocial adjustment in persons with disabilities. METHOD: The two
      primary databases containing the literature related to rehabilitation and
      disability issues (PsychINFO and MedLine) were searched to identify articles
      addressing the psychosocial impact of substance abuse in persons with
      disabilities. Eleven empirical articles specifically measuring the strength of
      the relationship between substance use and psychosocial outcomes in persons with
      disabilities were selected for analysis. RESULTS: Of the studies identified, five
      were related to spinal cord injury, three were related to traumatic brain injury,
      one was related to chronic back pain, one was related to HIV/AIDS, and one was
      related to persons with any type of disability. Each of the studies used
      different methodologies, measured substance abuse in different ways, and examined
      different psychosocial outcome variables. Examination of trends suggested that
      pre-injury substance abuse appears to be unrelated to acceptance of disability in
      persons with spinal cord injury and negatively associated with satisfaction in
      persons with traumatic brain injury. Recent substance abuse tends to have a
      detrimental effect on psychosocial outcomes across all disability groups.
      CONCLUSIONS: Future research, combined with appropriate pre-service and
      continuing education related to substance abuse and disability for rehabilitation
      practitioners, has the potential to lead to improved psychosocial outcomes in
      persons with disabilities.

PMID- 20156049
TI  - Rehabilitation in bariatrics: opportunities for practice and research.
AB  - PURPOSE: Obesity is associated with a wide range of chronic illnesses and
      disabilities familiar to rehabilitation researchers and practitioners. Obesity
      discourse in the area of rehabilitation science and practice is limited. METHOD:
      A meeting of rehabilitation researchers, practitioners, industry and decision
      makers was held for the purpose of identifying research and practice priorities
      in the area of bariatric rehabilitation. RESULTS: Areas of common ground in terms
      of the identification of gaps in research, practice and knowledge about obesity
      in the context of rehabilitation science were identified. Participants developed
      a concept for a bariatric rehabilitation treatment and research institute. A
      commitment to embark on priority action items was made. CONCLUSIONS: This article
      describes a process that successfully gathered a diverse group of researchers,
      clinicians, industries and decision makers for the purpose of collectively
      advancing the area of bariatric rehabilitation in Canada.

PMID- 20156050
TI  - The characterisation of gait patterns of people with multiple sclerosis.
AB  - BACKGROUND: There are relatively few reports describing gait patterns in multiple
      sclerosis (MS) and most are confined to the analysis of temporal distance
      parameters with some assessment of joint range of motion. The aim of this study
      was to perform a biomechanical characterisation of gait patterns among people
      with MS across a wide range of severity of ambulatory impairment. METHODS:
      Sixteen patients with MS were recruited for this study. Initially, the spasticity
      of lower limb muscle groups was measured and ambulatory ability was graded.
      Patients were then placed in two groups based on the level of severity of
      ambulatory ability. Kinematic, kinetic and EMG gait data from both MS groups were
      then compared to a control group of 10 healthy subjects. RESULTS: Patients with
      MS in both groups were found to walk with reduced gait speed, reduced maximum hip
      and knee extension, ankle plantarflexion angle and propulsive force compared to
      the control group. In general, the same gait impairments were found in both MS
      groups compared to the control group, and were greater for the more severely
      affected MS patient group. INTERPRETATION: This study highlights typical gait
      patterns of people with MS and provides an indication of common pathways in the
      degeneration of ambulatory ability as a consequence of disease progression. This
      information should enable improved clinical treatment of ambulation, as well as
      the prescription, or even design, of appropriate assistive devices.

PMID- 20156051
TI  - Musculoskeletal complaints, physical activity and health-related quality of life
      among patients with the Ehlers-Danlos syndrome hypermobility type.
AB  - PURPOSE: To investigate the musculoskeletal complaints, physical activity (PA)
      and health-related quality of life (HRQoL) in patients with the Ehlers-Danlos
      syndrome hypermobility type (EDS-HT). METHODS: Thirty-two female EDS-HT patients
      as defined by the Villefranche criteria and 32 gender- and age-matched healthy
      control subjects participated in the study. Data about musculoskeletal complaints
      were collected from a specific form developed for the study. Daily PA and HRQoL
      were evaluated by the Baecke questionnaire and the RAND 36-Item Health Survey
      (distributed by RAND), respectively. RESULTS: A significant presence of joint
      pain, joint dislocations, muscle cramps, tendinitis, fatigue and headache were
      revealed in the EDS-HT patient group. Joint pain was reported as the most
      frequent and most severe symptom. The habitual PA level was diminished in the
      patient group. Specifically, EDS-HT subjects had significantly lower sport
      participation, but a comparable leisure time excluding sports compared to the
      healthy control subjects. All eight HRQoL dimensions of the RAND-36 and both
      physical and emotional summary scores were significantly impaired in EDS-HT.
      CONCLUSIONS: EDS-HT is characterised by various severe musculoskeletal complaints
      and has a detrimental effect on the habitual level of PA and HRQoL, in both
      physical and psychosocial dimension. An appropriate treatment and management in
      healthcare is needed.

PMID- 20156052
TI  - Community ambulation before and after hip fracture: a qualitative analysis.
AB  - PURPOSE: This qualitative study explored mobility levels around the home and in
      the community before and after hip fracture. METHODS: Twenty-four people
      receiving rehabilitation after hip fracture were interviewed using an in-depth
      semi-structured format: 12 who were receiving rehabilitation as inpatients, and
      12 who had been discharged home from inpatient rehabilitation and were continuing
      therapy as outpatients. The recorded interviews were transcribed and coded
      independently by two researchers. From these codes themes were developed.
      RESULTS: Before their fracture, participants were independent about their houses,
      but their level of community ambulation had been reducing over recent months or
      years, often associated with another health problem. Participants who had
      returned home after inpatient rehabilitation for hip fracture reported much
      reduced levels of mobility both in their house and in the community compared with
      their pre-fracture performance. This reduced level of mobility was associated
      with psychological factors (fear, lack of confidence, frustration), physical
      factors (pain, the presence of another health problem) and social/environmental
      factors (reliance on daughter, and car). The level of optimism expressed by
      people receiving inpatient rehabilitation contrasted with the pessimism of those
      receiving outpatient rehabilitation. CONCLUSIONS: Patients living back in the
      community after hip fracture described a reduced level of functioning and a
      pessimism that contrasted with the optimism expressed by people who were still in
      the inpatient phase of rehabilitation. These findings, and the importance of
      psychological factors and social support, may be considered when designing
      rehabilitation strategies to support the successful transition of people to their
      community after hip fracture.

PMID- 20156053
TI  - Short-term supervised inpatient physiotherapy exercise protocol improves cardiac
      autonomic function after coronary artery bypass graft surgery--a randomised
      controlled trial.
AB  - OBJECTIVE: Coronary artery bypass grafting (CABG) is accompanied by severe
      impairment of cardiac autonomous regulation (CAR). This study aimed to determine
      whether a short-term physiotherapy exercise protocol post-CABG, during inpatient
      cardiac rehabilitation (CR), might improve CAR. DESIGN: Seventy-four patients
      eligible for CABG were recruited and randomised into physiotherapy exercise group
      (EG) or physiotherapy usual care group (UCG). EG patients underwent a short-term
      supervised inpatient physiotherapy exercise protocol consisting of an early
      mobilisation with progressive exercises plus usual care (respiratory exercises).
      UCG only received respiratory exercises. Forty-seven patients (24 EG and 23 UGC)
      completed the study. Outcome measures of CAR included linear and non-linear
      measures of heart rate variability (HRV) assessed before discharge. RESULTS: By
      hospital discharge, EG presented significantly higher parasympathetic HRV values
      [rMSSD, high frequency (HF), SD1)], global power (STD RR, SD2), non-linear HRV
      indexes [detrended fluctuation analysis (DFA)alpha1, DFAalpha2, approximate
      entropy (ApEn)] and mean RR compared to UCG (p<0.05). Conversely, higher values
      of mean HR, low frequency (LF) (sympathetic activity) and the LF/HF (global
      sympatho-vagal balance) were found in the UCG. CONCLUSIONS: A short-term
      supervised physiotherapy exercise protocol during inpatient CR improves CAR at
      the time of discharge. Thus, exercise-based inpatient CR might be an effective
      non-pharmacological tool to improve autonomic cardiac tone in patient's post
      CABG.

PMID- 20156054
TI  - Factor structure of the PANAS and the relationship between positive and negative
      affect in polio survivors.
AB  - AIM: This study examined the psychometric properties of the positive and negative
      affect schedule (PANAS) in a post-polio sample and the relationship of these
      affect the dimensions. METHOD: Exploratory factor analysis (EFA) was performed
      with sample 1 (randomly selected from the total sample), to examine the
      underlying dimensions of the PANAS. Confirmatory factor analyses (CFA) were
      performed with samples 2 and 1 to assess the fit of the models to the data. Model
      fit tests were based on the chi(2) likelihood ratio test, comparative fit index
      (CFI), and root mean square estimate of approximation (RMSEA). RESULTS: In the
      EFA phase, two factors were extracted and oblique rotation was applied to
      interpret pattern of loadings. In the CFA phase, both samples 1 and 2, model fit
      tests demonstrated that the models were unsatisfactory and indicated poor fit of
      the model to the observed data. Post-hoc model fitting of three error
      correlations as indicated by modification indices, proved a better fit for both
      samples. CONCLUSIONS: The results of the factor analyses suggested the
      possibility of a third dimension reflecting negative affect and that affect may
      consist of more than two general dimensions in the context of disability. In post
      polio population, some of the symptoms of negative affect may be caused by
      physical symptoms that are related to the disability experience.

PMID- 20156055
TI  - Safety of 3 different reintroduction regimens of antituberculosis drugs after
      development of antituberculosis treatment-induced hepatotoxicity.
AB  - BACKGROUND: Drug-induced hepatotoxicity (DIH) is the most common adverse drug
      reaction leading to interruption of antituberculosis treatment. Worldwide,
      different reintroduction regimens have been advocated, but no consensus
      guidelines are available. Reintroduction of antituberculosis drugs in patients
      with DIH has never been studied systematically. We aimed to compare the safety of
      3 different reintroduction regimens of antituberculosis drugs in patients with
      antituberculosis DIH. METHODS: A total of 175 patients with a diagnosis of
      antituberculosis DIH were randomized to receive 1 of 3 different predefined
      reintroduction regimens of antituberculosis drugs and were evaluated
      prospectively. Patients in arm I were given isoniazid, rifampicin, and
      pyrazinamide simultaneously at full dosage from day 1. In arm II, drugs were
      administered in a manner similar to that recommended in the American Thoracic
      Society guidelines for reintroduction. In arm III, drugs were administered in
      accordance with British Thoracic Society guidelines. RESULTS: Nineteen patients
      (10.9%) had recurrence of DIH during follow-up. Eight, 6, and 5 patients had
      recurrence of hepatitis in arms I, II, and III, respectively (P = .69). Of all
      the clinical and laboratory parameters, pretreatment serum albumin level was the
      only statistically significant predictor of future recurrence of DIH on
      reintroduction of antituberculosis drugs (P < .01). CONCLUSIONS: The recurrence
      rate of hepatotoxicity was not significantly different between the 3 groups.
      According to the findings of the present study, all 3 of the potentially
      hepatotoxic drugs (isoniazid, rifampicin, and pyrazinamide) can be reintroduced
      simultaneously at full dosage safely from day 1, especially for patients with
      bilateral extensive pulmonary tuberculosis, to halt disease transmission or to
      treat patients with life-threatening tuberculosis. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier number: NCT00405301.

PMID- 20156056
TI  - Challenges in reintroducing tuberculosis medications after hepatotoxicity.

PMID- 20156057
TI  - Lung cancer and diesel exhaust: a critical review of the occupational
      epidemiology literature.
AB  - The diesel exhaust (DE)-lung cancer hypothesis is evaluated. Diesel power became
      common after World War II, exposure was to traditional diesel exhaust (TDE)
      before 1988. In the next, 20 years, emissions were modified to new-technology
      diesel exhaust (NTDE) containing 1% of pre-1988 levels of diesel particulate
      matter (DPM). Nearly all pre-1990 studies were cohorts with primarily pre-diesel
      exposures. This review focuses on the proportion of cases with >20 years since
      initial DE exposure; strength of association; biological gradients; roles of
      chance, bias, and confounding; and consistency in 13 diesel studies. Five studies
      had adequate latency, six had a minority of workers with >20 years' latency, and
      in two studies most workers had inadequate latency. This pattern suggests too few
      relevant studies for evaluating the DE-lung cancer hypothesis. The 16 highest
      exposure categories showed 7 with probable associations (relative risk [RR] >
      1.5), 7 with improbable or no associations (RRs < 1.2), and 2 with possible
      associations (RRs 1.2-1.5). This random pattern with many weak RRs does not
      support the DE-lung cancer hypothesis. Ten of 34 exposure-response (E-R) analyses
      showed positive trends and 24 had indeterminate or negative trends. This small
      number of positive biological gradients does not support causality. Weight of
      evidence suggests 70% of studies are indeterminate, whereas 30% are positive or
      negative, indicating a lack of consistency. To support a traditional diesel
      exhaust-lung cancer hypothesis requires more studies with longer follow-up and
      quantitative E-R analyses.

PMID- 20156059
TI  - Sex and gender differences in travel-associated disease.
AB  - BACKGROUND: No systematic studies exist on sex and gender differences across a
      broad range of travel-associated diseases. METHODS: Travel and tropical medicine
      GeoSentinel clinics worldwide contributed prospective, standardized data on
      58,908 patients with travel-associated illness to a central database from 1 March
      1997 through 31 October 2007. We evaluated sex and gender differences in health
      outcomes and in demographic characteristics. Statistical significance for crude
      analysis of dichotomous variables was determined using chi2 tests with
      calculation of odds ratios (ORs) and 95% confidence intervals (CIs). The main
      outcome measure was proportionate morbidity of specific diagnoses in men and
      women. The analyses were adjusted for age, travel duration, pretravel encounter,
      reason for travel, and geographical region visited. RESULTS: We found
      statistically significant (P < .001) differences in morbidity by sex. Women are
      proportionately more likely than men to present with acute diarrhea (OR, 1.13;
      95% CI, 1.09-1.38), chronic diarrhea (OR, 1.28; 95% CI, 1.19-1.37), irritable
      bowel syndrome (OR, 1.39; 95% CI, 1.24-1.57), upper respiratory tract infection
      (OR, 1.23; 95% CI, 1.14-1.33); urinary tract infection (OR, 4.01; 95% CI, 3.34
      4.71), psychological stressors (OR, 1.3; 95% CI, 1.14-1.48), oral and dental
      conditions, or adverse reactions to medication. Women are proportionately less
      likely to have febrile illnesses (OR, 0.15; 95% CI, 0.10-0.21); vector-borne
      diseases, such as malaria (OR, 0.46; 95% CI, 0.41-0.51), leishmaniasis, or
      rickettsioses (OR, 0.57; 95% CI, 0.43-0.74); sexually transmitted infections (OR,
      0.68; 95% CI 0.58-0.81); viral hepatitis (OR, 0.34; 95% CI, 0.21-0.54); or
      noninfectious problems, including cardiovascular disease, acute mountain
      sickness, and frostbite. Women are statistically significantly more likely to
      obtain pretravel advice (OR, 1.28; 95% CI, 1.23-1.32), and ill female travelers
      are less likely than ill male travelers to be hospitalized (OR, 0.45; 95% CI,
      0.42-0.49). CONCLUSIONS: Men and women present with different profiles of travel
      related morbidity. Preventive travel medicine and future travel medicine research
      need to address gender-specific intervention strategies and differential
      susceptibility to disease.

PMID- 20156060
TI  - Short-course raltegravir intensification does not reduce persistent low-level
      viremia in patients with HIV-1 suppression during receipt of combination
      antiretroviral therapy.
AB  - BACKGROUND: Combination antiretroviral therapy suppresses but does not eradicate
      human immunodeficiency virus type 1 (HIV-1) in infected persons, and low-level
      viremia can be detected despite years of suppressive antiretroviral therapy.
      Short-course (28-day) intensification of standard antiretroviral combination
      therapy is a useful approach to determine whether complete rounds of HIV-1
      replication in rapidly cycling cells contribute to persistent viremia. We
      investigated whether intensification with the integrase inhibitor raltegravir
      decreases plasma HIV-1 RNA levels in patients receiving suppressive
      antiretroviral therapy. METHODS: Subjects (n = 10) with long-term HIV-1
      suppression receiving combination antiretroviral regimens had their regimens
      intensified for 4 weeks with raltegravir. Plasma HIV-1 RNA level was determined
      before, during, and after the 4-week intensification period, using a sensitive
      assay (limit of detection, 0.2 copies of HIV-1 RNA/mL of plasma). A 4-week
      intensification course was chosen to investigate potential HIV-1 replication in
      cells with relatively short (approximately 1-14-day) half-lives. RESULTS: There
      was no evidence in any subject of a decline in HIV-1 RNA level during the period
      of raltegravir intensification or of rebound after discontinuation. Median levels
      of HIV-1 RNA before (0.17 log10 copies/mL), during (0.04 log10 copies/mL), and
      after (0.04 log10 copies/mL) raltegravir intensification were not significantly
      different (P > .1 for all comparisons in parametric analyses). High-performance
      liquid chromatography and mass spectroscopy experiments confirmed that
      therapeutic levels of raltegravir were achieved in plasma during intensification.
      CONCLUSIONS: Intensification of antiretroviral therapy with a potent HIV-1
      integrase inhibitor did not decrease persistent viremia in subjects receiving
      suppressive regimens, indicating that rapidly cycling cells infected with HIV-1
      were not present. Eradication of HIV-1 from infected persons will require new
      therapeutic approaches. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT00618371.

PMID- 20156061
TI  - Fulminant infectious mononucleosis and recurrent Epstein-Barr virus reactivation
      in an adolescent.
AB  - We describe a unique case of fulminant infectious mononucleosis and recurrent
      Epstein-Barr virus reactivation presenting in an adolescent. Detailed assays of
      Epstein-Barr virus-specific T cell immunity revealed defects in the patient's T
      cell receptor signalling pathway characterized by a lack of interleukin-2 and
      CD25 expression, which may have contributed to her clinical course. Allogeneic
      stem cell transplantation reversed the clinical and laboratory phenotype.

PMID- 20156062
TI  - Guideline for prevention of catheter-associated urinary tract infections 2009.

PMID- 20156063
TI  - Catheter-acquired urinary tract infection: the once and future guidelines.

PMID- 20156064
TI  - Estimating attributable mortality due to nosocomial infections acquired in
      intensive care units.
AB  - BACKGROUND: The strength of the association between intensive care unit (ICU)
      acquired nosocomial infections (NIs) and mortality might differ according to the
      methodological approach taken. OBJECTIVE: To assess the association between ICU
      acquired NIs and mortality using the concept of population-attributable fraction
      (PAF) for patient deaths caused by ICU-acquired NIs in a large cohort of
      critically ill patients. SETTING: Eleven ICUs of a French university hospital.
      DESIGN: We analyzed surveillance data on ICU-acquired NIs collected prospectively
      during the period from 1995 through 2003. The primary outcome was mortality from
      ICU-acquired NI stratified by site of infection. A matched-pair, case-control
      study was performed. Each patient who died before ICU discharge was defined as a
      case patient, and each patient who survived to ICU discharge was defined as a
      control patient. The PAF was calculated after adjustment for confounders by use
      of conditional logistic regression analysis. RESULTS: Among 8,068 ICU patients, a
      total of 1,725 deceased patients were successfully matched with 1,725 control
      patients. The adjusted PAF due to ICU-acquired NI for patients who died before
      ICU discharge was 14.6% (95% confidence interval [CI], 14.4%-14.8%). Stratified
      by the type of infection, the PAF was 6.1% (95% CI, 5.7%-6.5%) for pulmonary
      infection, 3.2% (95% CI, 2.8%-3.5%) for central venous catheter infection, 1.7%
      (95% CI, 0.9%-2.5%) for bloodstream infection, and 0.0% (95% CI, -0.4% to 0.4%)
      for urinary tract infection. CONCLUSIONS: ICU-acquired NI had an important effect
      on mortality. However, the statistical association between ICU-acquired NI and
      mortality tended to be less pronounced in findings based on the PAF than in study
      findings based on estimates of relative risk. Therefore, the choice of methods
      does matter when the burden of NI needs to be assessed.

PMID- 20156065
TI  - Quantitative assessment of combination antimicrobial therapy against multidrug
      resistant bacteria in a murine pneumonia model.
AB  - BACKGROUND: Combination antimicrobial therapy is clinically used as a last-resort
      strategy to control multidrug-resistant bacterial infections. However, selection
      of antibiotics is often empirical, and conventional assessment of combined drug
      effect has not been correlated to clinical outcomes. Here, we report a
      quantitative method to assess combined killing of antimicrobial agents against 2
      multidrug-resistant bacteria. METHODS: Combined time-kill studies were performed
      using clinically achievable concentrations for each 2-agent combination against
      clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa.
      Bacterial burden observed at 24 h was mathematically modeled using a 3
      dimensional response surface. Subsequently, a neutropenic murine pneumonia model
      with simulated clinical dosing exposures was used to validate our quantitative
      assessment of combined killing. RESULTS: Different antimicrobial combinations
      were found to have varying efficacy against the multidrug-resistant bacteria. As
      predicted by our quantitative method, cefepime plus amikacin was found to be the
      most superior combination, which was evidenced by a reduction in tissue bacterial
      burden and prolonged survival of infected animals. CONCLUSIONS: The consistency
      between the predictions of the mathematical model and in vivo observations
      substantiated the robustness of our quantitative method. These data highlighted a
      novel and promising method to guide rational selection of antimicrobial
      combination in the clinical setting.

PMID- 20156066
TI  - Cutoffs of abdominal adipose tissue compartments as measured by magnetic
      resonance imaging for detection of cardiovascular risk factors in apparently
      healthy adult Asian Indians in North India.
AB  - BACKGROUND: We aimed to define cutoffs of abdominal adipose tissue depots [total
      abdominal adipose tissue (TAAT), intraabdominal adipose tissue (IAAT), and
      abdominal subcutaneous adipose tissue (SCAT)] in adult Asian Indians in North
      India. METHODS: We carried out a cross-sectional study that included 100 healthy
      adult Asian Indians. Anthropometric measurement (waist circumference, body mass
      index), metabolic profile [oral glucose tolerance test (OGTT), lipid profile],
      and imaging (for quantification of area of abdominal adipose tissue components
      using single slice magnetic resonance imaging) were done. Odds ratios (ORs) for
      detecting presence of greater than one cardiovascular (CV) risk factor were
      computed using tertiles of adipose tissue compartments and cutoffs were generated
      using receiver operating characteristics curve analysis. RESULTS: The gender
      specific cutoff limits for of TAAT, IAAT, and SCAT were 245.6 cm(2) (male) and
      203.46 cm(2) (female), 135.3 cm(2) (male) and 75.73 cm(2) (female), and 110.74
      cm(2) (male) and 134.02 cm(2) (female), respectively. For detection of CV risk
      factors, distinct gender differences were seen in ORs for SCAT [3.54 (95%
      confidence interval [CI], 1.10-11.46) and 6.6 (95% CI, 1.75-24.85) in males and
      females, respectively] but not for IAAT. CONCLUSIONS: The cutoffs of TAAT, IAAT,
      and SCAT generated for the first time in Asian Indians could be used for
      metabolic research, interethnic comparisons of adiposity and CV risk factors, and
      optimal selection of anthropometric parameters.

PMID- 20156067
TI  - Uncoupling between insulin and release of a D-chiro-inositol-containing
      inositolphosphoglycan mediator of insulin action in obese women With polycystic
      ovary syndrome.
AB  - BACKGROUND: Obese women with polycystic ovary syndrome (PCOS) manifest impaired
      insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan
      (DCI-IPG) insulin mediator during oral glucose tolerance testing (OGTT), which
      appears to be restored by the administration of metformin. This suggests that
      either obesity or PCOS is associated with a defect in the coupling of the
      stimulation of the insulin receptor by insulin to the release of the DCI-IPG
      mediator. The objective of this study was to compare the release of bioactive DCI
      IPG between normal nonobese women and obese PCOS women during stimulation with
      two different concentrations of insulin when glucose levels are clamped. METHODS:
      We performed a cross-sectional case-control study at the clinical research center
      of an academic medical center. A two-step euglycemic-hyperinsulinemic clamp was
      carried out in 8 nonobese normal and 8 obese PCOS women, during which DCI-IPG
      bioactivity was monitored. RESULTS: At baseline, PCOS women were significantly
      more obese, hyperinsulinemic, and insulin resistant than the controls. During the
      clamp studies, DCI-IPG bioactivity increased significantly over the first 45 min
      of the low-insulin step of the clamp in normal nonobese women (P = 0.046) and
      then decreased to baseline levels; DCI-IPG increased again after initiation of
      the high-insulin step (P = 0.029). Despite higher insulin levels during the clamp
      in PCOS women, DCI-IPG bioactivity remained flat throughout both insulin steps
      and was thus significantly lower than in controls during the initial periods of
      both steps. CONCLUSIONS: The coupling between insulin action and the release of
      the DCI-IPG mediator is selectively impaired in obese PCOS women, which may
      contribute to the insulin resistance in these women.

PMID- 20156068
TI  - Diagnostic criteria for metabolic syndrome: caucasians versus African-Americans.
AB  - BACKGROUND: Metabolic syndrome is a constellation of risk factors used to
      identify individuals at greatest risk for developing cardiovascular disease
      (CVD). Early diagnosis of CVD would benefit African-Americans (AA), who have a
      higher prevalence of and mortality rate from CVD compared to Caucasians (CA). Two
      definitions for metabolic syndrome were used to classify healthy CA and AA, and
      evaluate how other CVD risk factors [C-reactive protein (CRP), percent body fat,
      fitness level, insulin resistance, and non-high-density lipoprotein cholesterol
      (HDL-C)] changed metabolic syndrome classification. METHODS: Healthy AA (n = 97)
      and CA (n = 51) ranging from normal weight to obese, 18-45 years of age, with
      neither hypertension nor diabetes, were evaluated for cardiorespiratory fitness,
      height, weight, percent body fat, hip and waist circumference, blood pressure
      (BP), and fasting blood glucose, insulin, triglycerides, HDL, non-HDL-C, and CRP.
      Participants were classified as meeting the criteria for metabolic syndrome
      according to the National Cholesterol Education Program Adult Treatment Panel III
      2004 (NCEP ATP III) and the International Diabetes Federation (IDF) definitions.
      RESULTS: Significant ethnic differences (P < 0.01) in classification were noted
      for both metabolic syndrome definitions (NCEP ATP III, CA = 16.7% vs. AA = 5.7%;
      IDF, CA = 23.5% vs. AA = 8.2%). Ethnic differences were eliminated when fitness
      level or percent body fat was included as a criterion. CONCLUSIONS: If diagnosis
      of metabolic syndrome is intended for early recognition of CVD risk and slowing
      CVD development, current definitions for metabolic syndrome will not capture
      healthy AA. Health-care providers may consider assessing percent body fat and
      participation in regular exercise, because these criteria would help identify AA
      at risk.

PMID- 20156069
TI  - Ethnic disparities of the metabolic syndrome in population-based samples of
      german and Iranian adolescents.
AB  - BACKGROUND: Globalization of the western lifestyle may contribute to worldwide
      increases of adiposity and type 2 diabetes. In combination with genetic
      influences, this results in different prevalence rates among different
      ethnicities, particularly at younger ages. Since 2007, the unified pediatric
      definition of the metabolic syndrome by the International Diabetes Federation
      (IDF) has allowed a global comparison of the prevalence. Therefore, we compared
      the prevalence of the metabolic syndrome and its components in two large
      representative samples of adolescents in Germany and Iran. METHODS: We used data
      from 3,647 German adolescents aged 10-15 years old participating in the German
      PEP Family Heart Study and 2,728 Iranians in the same age range participating in
      the CASPIAN Study. RESULTS: The metabolic syndrome was four times more prevalent
      in Iranian (2.1%) than in German (0.5%) adolescents. The prevalence of three
      components of the metabolic syndrome was significantly (P < 0.0001) higher in
      Iranian than in German adolescents-the prerequisite abdominal obesity (11.1% vs.
      11.4% vs 1.9%), low-serum high-density lipoprotein cholesterol (HDL-C) (41.9% vs.
      7.2%) and hypertriglyceridemia (7.2% vs. 11.4%). CONCLUSIONS: The prevalence of
      the metabolic syndrome according to pediatric IDF criteria and its three main
      components differed considerably in two large ethnicities. The clinical impacts
      of these findings should be confirmed in future longitudinal studies.

PMID- 20156070
TI  - Metabolic syndrome and angiographic coronary artery disease prevalence in
      association with the Framingham risk score.
AB  - BACKGROUND: The association of metabolic syndrome with coronary artery disease
      (CAD) has been studied extensively. However, little is known about the effect of
      Framingham risk score (FRS) and metabolic syndrome components on the association
      of metabolic syndrome with angiographically significant CAD. Our aim was to
      investigate whether that relationship is influenced by individual's 10-year CAD
      risk profile as assessed by FRS. Furthermore, we sought to elucidate whether
      metabolic syndrome is associated with angiographically significant CAD
      independently of its individual components. METHODS: We studied a consecutive
      sample of 150 patients undergoing coronary angiography for the evaluation of
      chest pain. Metabolic syndrome was defined according to the revised National
      Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria,
      and the 10-year CAD risk was estimated by the FRS. RESULTS: Metabolic syndrome
      patients had a 2-fold higher CAD prevalence compared to those without metabolic
      syndrome [odds ratio (OR), 2.004; 95% confidence interval (CI), 1.029-3.905] but
      this finding was attenuated after adjustment for FRS (OR, 1.770; 95% CI, 0.872
      3.594). Stratification of patients into three groups according to FRS revealed
      that metabolic syndrome predictive ability was confined in those being at <10% 10
      year CAD risk. Including metabolic syndrome and its individual components into
      the same logistic regression model, only the glucose criterion was an independent
      predictor of angiographically significant CAD (OR, 4.137; 95% CI, 1.477-11.583).
      CONCLUSIONS: Metabolic syndrome is an independent determinant of angiographically
      significant CAD only among those individuals at low 10-year risk for future
      coronary events. Individual components of the syndrome, such as impaired fasting
      glucose, have a stronger association with CAD than the syndrome as a whole.

PMID- 20156071
TI  - Predicting adult body mass index-specific metabolic risk from childhood.
AB  - BACKGROUND: Metabolic risk varies within adult body mass index (BMI) categories;
      however, the development of BMI-specific metabolic risk from childhood is
      unknown. METHODS: The sample included 895 adults (20-38 years of age; 43% male,
      34% black) from the Bogalusa Heart Study (1995-2002), who had been measured as
      children (5-18 years of age) in 1981-1982. Adult metabolic risk was assessed
      using two definitions: Cardiometabolic risk factor clustering (RFC) included two
      or more abnormal risk factors [blood pressure, high-density lipoprotein
      cholesterol (HDL-C), triglycerides, and fasting glucose] and insulin resistance
      (IR), comprising the top quartile of the homeostasis model of insulin resistance
      (HOMA-IR) distribution. Logistic regression, within BMI categories, was used to
      predict adult metabolic risk from childhood mean arterial pressure (MAP), HDL-C,
      low-density lipoprotein cholesterol (LDL-C), glucose, and triglycerides.
      Covariates included childhood age, race, sex, adult BMI, and length of follow-up.
      RESULTS: The prevalence of the adult abnormal metabolic risk profile varied by
      definitions of metabolic risk (normal weight, 5%-9%; overweight, 15%-23%; and
      obese, 40%-53%). The adult abnormal profile was associated with higher childhood
      LDL-C [IR, odds ratio (OR), 1.95; 95% confidence interval (CI), 1.06-3.58) and
      insulin (IR, OR, 1.69; CI, 1.10-2.58) in normal-weight adults; lower childhood
      HDL-C in overweight adults (RFC, OR, 0.61; CI, 0.40-0.94); and higher childhood
      MAP (RFC, OR, 1.75; CI, 1.24-2.47) and glucose (IR, OR,1.38; CI, 1.06-1.81) in
      obese adults. CONCLUSIONS: Some childhood metabolic risk factors are moderately
      associated with adult BMI-specific metabolic risk profiles. The ability to
      identify children with high future adult cardiovascular risk may initiate early
      treatment options.

PMID- 20156072
TI  - Does the presence of metabolic syndome influence weight loss in obese and
      overweight women?
AB  - BACKGROUND: It is known that weight loss is beneficial for obese and overweight
      subjects with metabolic syndrome. Very few data exist, however, about whether the
      presence of metabolic syndrome and insulin resistance (IR) influence the response
      of these subjects to weight-reducing interventions. The current study intends to
      examine whether the presence of metabolic syndrome and its components could
      influence weight loss in obese and overweight women during a short-term, dietary
      based intervention program. METHODS: A total of 107 women aged 49.1 +/- 13.5
      years old, with a body mass index (BMI) greater than 25 were studied. The
      subjects were prescribed a low-fat diet plus weight-reducing drugs when
      necessary. RESULTS: After 3 months, the subjects with metabolic syndrome lost
      more weight than those without (6.62% vs. 4.50%; P < 0.05). There was a positive
      correlation between the percentage of weight loss and the number of the
      components of metabolic syndrome present at baseline (Spearman rho = 0.329; P <
      0.01). Furthermore, patients in the quartile with the highest homeostasis model
      assessment index (HOMA-index) lost more weight than the remaining subjects (8.17%
      +/- 3.34 vs. 5.59% +/- 3.87; P < 0.05). These results were significant, even
      after adjustment for the medical treatment prescribed. CONCLUSIONS: Obese and
      overweight patients with metabolic syndrome showed a greater reduction of their
      body weight, compared to the patients without metabolic syndrome. The components
      of the metabolic syndrome present at baseline correlated positively with the
      percentage of the weight loss. Finally, the patients with the highest levels of
      HOMA-index at baseline lost significantly more weight than those with lower
      levels of this parameter.

PMID- 20156073
TI  - Antihypertensive treatment, high triglycerides, and low high-density lipoprotein
      cholesterol and risk of ischemic heart disease mortality: a 16-year follow-up in
      the Copenhagen male study.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that metabolic
      syndrome dyslipidemia is a major risk factor for ischemic heart disease (IHD)
      mortality among men taking antihypertensive medication. METHODS: This was a 16
      year follow up of 2,986 men 53-75 years old without overt cardiovascular disease;
      357 men used antihypertensive medicine. Potential risk factors were type of
      baseline medication, blood pressure, diabetes, fasting serum triglycerides (TG),
      high-density lipoprotein (HDL-C) and total cholesterol, glucosuria,
      electrocardiogram (ECG) changes, cancer history, body mass index, alcohol and
      tobacco use, leisure time physical activity, social class, and age. The main
      outcome was IHD mortality. RESULTS: Men treated for hypertension had a two-fold
      higher cumulative incidence of IHD mortality during the follow up compared to
      other men (12.0% vs, 5.8%). Dyslipidemia was defined as TG >or=1.70 mmol/L or HDL
      C <or=1.03 mmol/L. Among men without any dyslipidemia (n = 159 or 46%), in Cox
      analysis adjusted for age only, the hazard ratio (HR) with 95% confidence
      interval (CI) for IHD mortality was 1.2 (0.6-2.3) compared to untreated
      normotensives (n = 1,953). Among men with one dyslipidemia (n = 116 or 34%) HR
      was 2.2 (1.2-4.0), and among men with combined dyslipidemia (n = 71 or 20%) HR
      was 6.0 (3.5-10.2). Adjustment for relevant confounders attenuated the three HRs
      to 0.8 (0.4-1.7), 1.6 (0.9-3.1), and 4.5 (2.5-8.2), respectively. Measured blood
      pressure was not associated with IHD mortality risk among men on antihypertensive
      medication. CONCLUSIONS: TG and HDL-C dyslipidemia were strong effect modifiers.
      Men on antihypertensive medication had no increased risk of IHD mortality
      compared to untreated normotensive men, provided they were free from high TG and
      low HDL-C dyslipidemia.

PMID- 20156074
TI  - Correlates of the metabolic syndrome among a sample of women in the San Juan
      Metropolitan area of Puerto Rico.
AB  - BACKGROUND: The metabolic syndrome is an interaction of risk factors that may
      lead to cardiovascular disease and type 2 diabetes. METHODS: Given the need for
      data in Puerto Rico, this cross-sectional study aimed to determine the
      association between demographic, lifestyles, and reproductive characteristics and
      the metabolic syndrome among a sample of women (N = 564) in the San Juan
      Metropolitan Area. The metabolic syndrome was defined based on the revised
      National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)
      criteria. RESULTS: In multivariate logistic regression models, women aged 40-59
      and 60-79 years were 3.03 [95% confidence interval (CI), 1.70, 5.40] and 7.05
      (95% CI, 3.69, 13.49) times more likely, respectively, to have the metabolic
      syndrome as compared to those aged 21-39 years. A dose-response relationship was
      also observed between body mass index (BMI) and metabolic syndrome. Physical
      activity reduced the odds for metabolic syndrome [prevalence odds ratios (POR) =
      0.64; 95% CI, 0.41, 1.01]; however, this association was marginally significant
      (P = 0.05). Among reproductive characteristics, only women who had a history of
      gestational diabetes (GDM) were 2.14 (95% CI, 1.02, 4.51) times more likely to
      have metabolic syndrome. CONCLUSIONS: Consistent with previous studies, increased
      age and BMI, physical inactivity, and GDM are associated with the metabolic
      syndrome in this population. This information is relevant for the development of
      preventive interventions for the metabolic syndrome.

PMID- 20156075
TI  - Elevated liver enzymes in metabolic syndrome are associated with coronary
      stenosis in a Tunisian population.
AB  - BACKGROUND: Recently, elevated liver enzymes have attracted great interest as
      potential novel markers of cardiovascular risk. The aim of this study was to
      investigate if there is a relationship between elevated liver enzymes and
      coronary stenosis associated with metabolic syndrome in a Tunisian population.
      METHODS: We enrolled 192 patients who underwent coronary angiography. Significant
      coronary stenosis (SCS) was diagnosed in the presence of coronary stenosis with
      lumenal narrowing >or=50%. Metabolic syndrome was defined according to the
      International Diabetes Federation criteria. RESULTS: Frequencies of subjects with
      liver enzyme activities belonging to quartile 4 were higher in the group with
      metabolic syndrome. Association of SCS with metabolic syndrome was more
      significant in the quartile 4 of gamma-glutamyl transferase (GGT) and alanine
      aminotransferase (ALT). Odds ratios of SCS associated with metabolic syndrome
      were: [1.40 (0.66-2.9) for quartile 1 versus 4.20 (1.3-9.9) for quartile 4 of
      GGT; 1.52 (0.29-3.7) for quartile 1 vs. 5.30 (1.39-18.9) for quartile 4 of ALT].
      CONCLUSIONS: Elevated liver enzyme activity was associated with metabolic
      syndrome and only GGT and ALT seem to be associated with an increase of the
      coronary stenosis in the studied population with metabolic syndrome.

PMID- 20156076
TI  - Metabolic syndrome does not predict an increased risk of coronary disease in
      patients with traditional risk factors referred for stress imaging study.
AB  - BACKGROUND: The impact of metabolic syndrome on the prediction of coronary artery
      disease (CAD) in subjects with multiple traditional risk factors is unknown.
      METHODS: We enrolled 2,626 consecutive subjects who underwent clinically
      indicated stress imaging studies using echocardiography or single-photon emission
      computed tomography (SPECT) myocardial perfusion. Patients with known CAD were
      excluded leaving 1256 subjects. Metabolic syndrome was defined by National
      Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria.
      The number of traditional risk factors and the presence of metabolic syndrome
      were compared with the results of stress imaging. Logistic regression analysis
      was used to assess the impact of metabolic syndrome on CAD prevalence in subjects
      with limited (<or=2) traditional risk factors and multiple (>or=3) risk factors.
      RESULTS: Metabolic syndrome was present in 540 (43%) of subjects. Presence of
      metabolic syndrome was associated with a nonsignificant 3%-4% increase in overall
      prevalence of CAD. Metabolic syndrome did not increase the prevalence of CAD in
      those with multiple (>or=3) traditional risk factors (metabolic syndrome 25% vs.
      no metabolic syndrome 21%, P = 0.62) or in those with limited (<or=2) risk
      factors (metabolic syndrome 19% vs. no metabolic syndrome 16%, P = 0.13). The
      presence of multiple versus limited risk factors had poor accuracy for prediction
      of CAD with area under the receiver operating curve (ROC) = 0.52. Information on
      the presence or absence of metabolic syndrome did not improve identification of
      CAD, ROC area of 0.54, P = not significant (N.S.). None of the five individual
      components of metabolic syndrome showed significant association with CAD.
      CONCLUSIONS: The addition of metabolic syndrome to traditional risk factors does
      not increase the prevalence of CAD determined by stress imaging.

PMID- 20156077
TI  - Epicardial fat tissue thickness correlates with endothelial dysfunction and other
      cardiovascular risk factors in patients with metabolic syndrome.
AB  - BACKGROUND: Epicardial adipose tissue has shown to be related to cardiovascular
      risk. The aim of this study is to investigate the relationship between epicardial
      adiposity and endothelial function in metabolic syndrome. METHODS: Fifty patients
      with metabolic syndrome were recruited. Anthropometric measurements, fasting
      blood glucose, insulin, lipid profile, high-sensitivity C-reactive protein
      (hsCRP), fibrinogen, apolipoprotein A (Apo A), Apo B1, and lipoprotein (a)
      [Lp(a)] were determined. Homeostasis model assessment of insulin resistance (HOMA
      IR) was calculated. Epicardial fat thickness was measured via two-dimensional M
      mode echocardiography. Endothelial function was assessed as flow-mediated
      dilatation at the brachial artery. RESULTS: Epicardial fat tissue thickness was
      shown to be correlated negatively with FMD and positively with age, diastolic
      blood pressure, hsCRP, fibrinogen, HOMA-IR, and lipid parameters. Multiple
      regression analysis showed epicardial fat tissue thickness to be an independent
      factor influencing the endothelial function. CONCLUSIONS: Epicardial fat tissue
      may be a useful parameter in the assessment of patients with metabolic syndrome.

PMID- 20156078
TI  - Hypertensive treatment in patients with metabolic syndrome.
AB  - The prevalence of obesity, hypertension, and type 2 diabetes mellitus-in other
      words, the metabolic syndrome-is increasing in the United States. In this
      setting, it is important to understand the effects of antihypertensives on
      parameters of the metabolic syndrome in addition to glucose metabolism. Here the
      authors review pertinent clinical studies.

PMID- 20156079
TI  - Retinol-binding protein 4 in patients with gestational diabetes mellitus.
AB  - OBJECTIVE: It is still unknown if serum retinol-binding protein 4 (RBP4) relates
      to metabolic control and the occurrence of gestational diabetes mellitus (GDM).
      We studied RBP4 levels in patients with insulin-treated GDM and healthy pregnant
      women twice during pregnancy. METHODS: Sixty-three women with GDM and 38 healthy
      pregnant women were included. Serum RBP4 levels were measured at 24-28 weeks of
      gestation and 8 weeks later. Patients with GDM were treated with insulin.
      RESULTS: Serum RBP4 levels increased significantly between the two measurements
      in patients with GDM (p = 0.03). In patients with GDM, RBP4 concentrations at 33
      weeks of gestation correlated positively with mean blood glucose, hemoglobin A1c
      values, and cord blood insulin values right after delivery. Regression analyses
      showed that the diagnosis of GDM (p = 0.04) and hemoglobin A1c levels (p < 0.001)
      were related to RBP4 levels at 33 weeks of gestation. CONCLUSIONS: Serum RBP4
      levels increase during pregnancy in patients with insulin-treated GDM.

PMID- 20156080
TI  - Factors associated with control of hypertension, hypercholesterolemia, and
      diabetes among low-income women in West Virginia.
AB  - BACKGROUND: Adequate control of cardiovascular risk factors, such as
      hypertension, hypercholesterolemia, and diabetes, requires management. Low-income
      women living in rural areas with limited health services may experience special
      challenges in managing chronic conditions. METHODS: In 2008, we conducted an
      analysis of the baseline, cross-sectional survey of 733 uninsured, low-income,
      rural women aged 40-64 years participating in the Well-Integrated Screening and
      Evaluation for Women Across the Nation (WISEWOMAN) project in West Virginia to
      characterize prevalence, treatment, and control of hypertension,
      hypercholesterolemia, and diabetes. Data were collected from 2004 to 2007.
      RESULTS: About 56% of the women had hypertension (38% of which was untreated or
      uncontrolled), 45% had hypercholesterolemia (31% of which was untreated or
      uncontrolled), and 19% had diabetes (26% of which was untreated or uncontrolled).
      Multivariable analyses showed that those with a regular physician were less
      likely than those without a physician to have uncontrolled hypertension (adjusted
      odds ratio [AOR] 0.34, 95% CI 0.13-0.88) and hypercholesterolemia (AOR 0.14, 95%
      CI 0.04-0.47). Education level was also a significant predictor for uncontrolled
      hypertension, and physical activity level (measured by total metabolic equivalent
      [MET] hours) significantly predicted uncontrolled hypercholesterolemia (AOR 1.01,
      95% CI 1.001-1.02). For diabetes, race/ethnicity was the main predictor; white
      women were less likely than other groups to have untreated or uncontrolled
      diabetes. CONCLUSIONS: High proportions of women in the WV-WISEWOMAN project had
      uncontrolled hypertension, hypercholesterolemia, and diabetes at baseline. These
      study results should be used to inform programs seeking to increase access to
      health services in order to reduce consequences of uncontrolled chronic
      conditions.

PMID- 20156082
TI  - Recognizing and treating urogenital atrophy in postmenopausal women.
AB  - Urogenital atrophy resulting from postmenopausal estrogen deficiency has numerous
      clinical effects, including vaginal dryness, sexual dysfunction, urinary
      incontinence, and recurrent urinary tract infections (UTIs), all of which can
      cause significant distress and reduction in quality of life. Although nearly one
      third to one half of postmenopausal women experience these symptoms, they are
      often overlooked because patients may be reluctant to discuss them and clinicians
      fail to screen for them. As these symptoms are unlikely to resolve without
      treatment, the prompt diagnosis and treatment of urogenital atrophy is essential.
      Estrogen therapy, administered either locally or systemically, provides
      significant relief from symptoms related to urogenital atrophy. However, systemic
      estrogen therapy is contraindicated in some women and may not be accepted in
      women without other menopausal symptoms. Local low-dose vaginal estrogen therapy,
      in the form of vaginal estrogen tablets, creams, or rings, has been shown to
      reduce dyspareunia and vaginal dryness, restore vaginal pH, and restore normal
      vaginal cytology. All forms of vaginal estrogen therapy are effective and well
      tolerated, although vaginal tablets and rings may have fewer adverse effects and
      have higher rates of adherence than creams.

PMID- 20156081
TI  - A qualitative study of faculty members' views of women chairs.
AB  - BACKGROUND: Concurrent with the evolving role of the department chair in academic
      medicine is the entry of women physicians into chair positions. Because implicit
      biases that stereotypically masculine behaviors are required for effective
      leadership remain strong, examining faculty members' perceptions of their chair's
      leadership in medical school departments with women chairs can provide insight
      into the views of women leaders in academic medicine and the complex ways in
      which gender may impact these chairs' leadership style and actions. METHODS: We
      conducted semistructured interviews with 13 male and 15 female faculty members
      representing all faculty tracks in three clinical departments chaired by women.
      Inductive, qualitative analysis of the subsequent text allowed themes to emerge
      across interviews. RESULTS: Four themes emerged regarding departmental
      leadership. One dealt with the leadership of the previous chair. The other three
      described the current chair's characteristics (tough, direct, and transparent),
      her use of communal actions to help support and mentor her faculty, and her
      ability to build power through consensus. Because all three chairs were early in
      their tenure, a wait and see attitude was frequently expressed. Faculty generally
      viewed having a woman chair as an indication of positive change, with potential
      individual and institutional advantages. CONCLUSIONS: This exploratory study
      suggests that the culture of academic medicine has moved beyond questioning women
      physicians' competence to lead once they are in top organizational leadership
      positions. The findings are also consonant with experimental research indicating
      that women leaders are most successful when they pair stereotypic male (agentic)
      behaviors with stereotypic female (communal) behaviors. All three chairs
      exhibited features of a transformational leadership style and characteristics
      deemed essential for effective leadership in academic medicine.

PMID- 20156083
TI  - Provider advice about weight loss and physical activity in the postpartum period.
AB  - OBJECTIVE: To explore the association between healthcare provider advice about
      weight loss and physical activity in the postpartum period and weight retention
      and activity levels in women assessed at 3 months postpartum. METHODS: Using data
      from a prospective cohort study, we explored the association of advice with
      postpartum weight retention and activity levels in 688 women at 3 months
      postpartum. Data from home visits included anthropometric measurements and
      information collected from sociodemographic, health behavior, and psychosocial
      questionnaires. Weight retention was calculated as weight at 3 months postpartum
      minus prepregnancy weight; activity levels and advice were based on maternal self
      report. Linear regression and Poisson regression were used to explore
      associations. RESULTS: The majority of the population was white (76%), had a
      greater than high school education (83%), and had an income >185% of the federal
      poverty level (81%). Women ranged in age from 17 to 48 years. Most women reported
      receiving no weight loss (89.1%) and no physical activity advice (77.4%) from a
      healthcare provider during the 3-month postpartum period. After adjustment, we
      found no association between provider advice and weight retention. When compared
      with those who reported no advice, following provider advice showed an
      association with recreational activity above the median (RR 1.50, 95% confidence
      interval [CI] 1.24, 1.80). CONCLUSIONS: Provider advice may influence physical
      activity but may not be enough to help postpartum women lose pregnancy weight.
      Instead, women may benefit more from individualized counseling and follow-up
      beyond the usual 6-week postpartum visit.

PMID- 20156084
TI  - Women's preference for receiving abortion in primary care settings.
AB  - BACKGROUND: Abortion is increasingly being incorporated into primary care
      training programs. It remains unclear if women, given the option, would accept
      and access these services with their primary care provider. METHODS: An anonymous
      survey was administered to 299 women at two abortion clinics in New York and
      Chicago. RESULTS: One hundred seventy-four (58.2%) respondents theoretically
      would choose their primary care clinic for their abortion procedure, with more
      Chicago participants than New York participants choosing primary care. After
      adjusting for other variables, only being very or somewhat comfortable with one's
      primary care provider regarding issues of pregnancy prevention and birth control
      predicted the choice of primary care for abortion services. CONCLUSIONS: The
      majority of women surveyed theoretically would choose to have a procedure at
      their primary care clinic. There were some regional differences between New York
      and Chicago. Although many variables used in this study did not explain the
      respondents' preferences, the primary care clinic as site for abortion care
      appears to be an important potential option for many women. Primary care training
      programs should teach full-spectrum reproductive healthcare to help meet the
      needs of their patients.

PMID- 20156085
TI  - Microarray analysis and draft genomes of two Escherichia coli O157:H7 lineage II
      cattle isolates FRIK966 and FRIK2000 investigating lack of Shiga toxin
      expression.
AB  - The existence of two separate genetic lineages of Escherichia coli O157:H7 has
      previously been reported, and research indicates that lineage I could be more
      pathogenic toward human hosts than lineage II. We have previously shown that
      lineage I as a group expresses higher levels of Shiga toxin 2 (Stx2) than lineage
      II. To help evaluate why lineage II strains do not express appreciable levels of
      this toxin, whole-genome microarrays were performed using Agilent custom
      microarrays. Gene expression of the two representative bovine lineage II strains
      (FRIK966 and FRIK2000) were compared with gene expression of E. coli O157:H7
      EDL933 (lineage I clinical type strain). Missing or differentially expressed
      genes and pathways were identified. Quantitative reverse transcription-polymerase
      chain reaction was performed to validate the microarray data. Draft genomes of
      FRIK966 and FRIK2000 were sequenced using Roche Applied Science/454 GS-FLX
      technology shotgun and paired-end approaches followed by de novo assembly. These
      assemblies were compared with the lineage I genome sequences from E. coli O157:H7
      EDL933. The bacteriophage 933W, which encodes the Stx2 genes, showed a notable
      repression in gene expression. Polymerase chain reaction primers, based upon
      EDL933 genomic information, were also designed against all of the potentially
      missing genes of this bacteriophage. Most of the structural genes associated with
      the bacteriophage were found to be absent from the genome of the two bovine
      strains. These analyses, combined with evaluation of the genomic information,
      suggest that transposon (IS629) rearrangements may be associated with disruption
      of the bacteriophage genome in the FRIK strains. The results support the
      hypothesis that lineage II strains may be less of a risk as human foodborne
      pathogens. The microarray and genome data have been made available to the
      scientific community to allow continuing analysis of these cattle-isolated
      lineage II genomes and their gene expression.

PMID- 20156086
TI  - Development of a multiplex real-time polymerase chain reaction for simultaneous
      detection of enterohemorrhagic Escherichia coli and enteropathogenic Escherichia
      coli strains.
AB  - A multiplex real-time polymerase chain reaction (PCR) was developed for the
      simultaneous detection of genes encoding intimin (eae) and all variants of Shiga
      toxins 1 and 2 (stx1 and stx2) in diagnostic samples. The uidA gene encoding a
      beta-glucuronidase specific for Escherichia coli and Shigella spp. was included
      in the multiplex PCR assay as an internal amplification control. The multiplex
      PCR was tested on 30 E. coli reference strains and 174 diagnostic samples already
      characterized as harboring stx1, stx2, and eae genes. The multiplex PCR correctly
      detected the genes in all strains examined. No cross reaction was observed with
      68 strains representing other gastrointestinal pathogens, normal gastrointestinal
      flora, or closely related bacteria, reflecting 100% specificity of the assay. The
      detection limits of the multiplex PCR were 5 genome equivalents for stx2 and 50
      genome equivalents for eae and stx1.

PMID- 20156087
TI  - Attribution of human Listeria monocytogenes infections in England and Wales to
      ready-to-eat food sources placed on the market: adaptation of the Hald Salmonella
      source attribution model.
AB  - Human listeriosis is a rare but serious foodborne disease, with high morbidity
      and mortality in vulnerable populations (e.g., pregnant women, the elderly, and
      the immunocompromised). The disease is predominantly caused by the consumption of
      contaminated ready-to-eat foods. Since 2001, an increase in the number of
      listeriosis cases has been observed in several European Union countries,
      including England and Wales, predominantly in the over-60s population. The cause
      of this selective increased incidence is unknown. The Hald Salmonella Bayesian
      source attribution model was adapted to determine the potential of this approach
      to quantify the contribution of different food sources to the burden of human
      listeriosis in England and Wales from 2004 to 2007. The most important food
      sources for the overall population were multicomponent foods (sandwiches and
      prepacked mixed salad vegetables) (23.1%), finfish (16.8%), and beef (15.3%).
      Attribution of major sources of infection was similar for the elderly population
      (>or=60 years old, multicomponent foods [22.0%], finfish [14.7%], and beef
      [13.6%]). For pregnancy-associated cases, beef (12.3%), milk and milk products
      (11.8%), and finfish (11.2%) were more important sources of infection. The
      adapted model also showed that the serotype 4b was associated with relatively
      more human infections than that of other serotypes; further, the subtype 4b
      amplified fragment-length polymorphism V was associated with more pregnancy
      associated cases than other subtypes of 4b. This approach of quantifying the
      contribution of various food sources to human listeriosis provides a useful tool
      in food safety risk analysis, and underlines the need for further emphasis to be
      given to the reduction of Listeria monocytogenes in high-risk foods, such as
      multicomponent foods, which are consumed without any further treatment. The need
      for targeted dietary advice for the elderly population is also highlighted.

PMID- 20156088
TI  - Epidemiology and epizootology of cystic echinococcosis in Romania 1862-2007.
AB  - Infections with cestodes from genus Echinococcus are usually acquired by oral
      ingestion of eggs, direct contact with carriers, and contaminated food
      (especially vegetables) or water. Echinococcosis, previously characterized as a
      malady of medical importance only, depends upon veterinary solutions and faces
      political obstacles; it is considered the most important zoonotic disease in
      Romania. As a result of the increased number of human and animal cases, Romania
      was framed in the forefront of the European countries and among the first
      countries worldwide in 1995. The present paper is the first international
      systematized review concerning echinococcosis in Romania. It covers a period of
      146 years, beginning in 1862, when the first case of human hydatid disease was
      mentioned in medical annals, until 2007 and aims at overviewing and analyzing
      data provided by major studies from different fields of human and veterinary
      medicine. Authors also present unpublished data of a 37-year surveillance
      performed in a reference infectious disease hospital. During the period 1979
      1988, 8557 patients were hospitalized for hydatid disease requiring 210,057 days
      of health care, and 516 fatalities (6.03%) were registered. The prevalence of the
      disease in livestock during the period 1983-1994 varied between 24.3% and 92.9%
      in sheep, 31.2% and 43.6% in cattle, and 20.4% and 73.8% in swine. The economic
      losses in animals are very high due not only to increased mortality rates but
      also to weight loss and decreased productivity. Epidemiological data available
      showed that at least one person from 45.5% of Romanian localities underwent
      surgery for cystic echinococcosis. The information presented outlines the
      severity of the situation from human- and livestock-associated cystic
      echinococcosis in Romania. Control programs based on combinations of animal
      vaccination, dehelmintization of dogs, and education programs should be
      implemented to achieve effective prevention of disease transmission.

PMID- 20156089
TI  - Evidence-based intervention to reduce access barriers to cervical cancer
      screening among underserved Chinese American women.
AB  - OBJECTIVE: The primary objective of the present study was to evaluate the effects
      of a community-based pilot intervention that combined cervical cancer education
      with patient navigation on cervical cancer screening behaviors among Chinese
      American women residing in New York City. METHODS: Chinese women (n = 134) who
      had not had a Pap test within the previous 12 months were recruited from four
      Asian community-based organizations (CBOs). Women from two of the CBOs received
      the intervention (n = 80) consisting of education, interaction with a Chinese
      physician, and navigation assistance, including help in identifying and accessing
      free or low-cost screening services. The control group (n = 54) received
      education delivered by Chinese community health educators and written materials
      on general health and cancer screening, including cervical cancer, the Pap test,
      and information about sites that provided free screening. Study assessments were
      obtained in-person at baseline and postintervention. Screening behavior was self
      reported at 12-month postintervention and verified by medical staff. RESULTS: In
      the 12-month interval following the program, screening rates were significantly
      higher in the intervention group (70%) compared to the control group (11.1%).
      Hierarchical logistic regression analyses indicated that screening behavior was
      associated with older age (OR = 1.08, 95% CI = 1.01-1.15, p < .05). In addition,
      women with poorer English language fluency (OR = 0.30, 95% CI = 0.10-0.89, p <
      .05) and who did not have health insurance were less likely to obtain screening
      (OR = 0.15, 95% CI = 0.02-0.96, p < .05). Among health beliefs, greater perceived
      severity of disease was positively associated with screening behavior (OR = 4.26,
      95% CI = 1.01-18.04, p < .05). CONCLUSIONS: Community-based programs that provide
      combined education and patient navigation may be effective in overcoming the
      extensive linguistic and access barriers to screening faced by Chinese American
      women.

PMID- 20156090
TI  - Ongoing barriers to HIV testing during pregnancy: a need for media campaigns
      addressing low knowledge about perinatal HIV transmission among women in the
      United States.

PMID- 20156091
TI  - Patient-reported outcomes in virologically suppressed, HIV-1-Infected subjects
      after switching to a simplified, single-tablet regimen of efavirenz,
      emtricitabine, and tenofovir DF.
AB  - A randomized, open-label, multicenter study was conducted to evaluate the
      therapeutic switch to a single-tablet formulation of
      efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) among virologically
      suppressed, HIV-1-infected subjects. Eligible subjects on stable antiretroviral
      therapy (ART) with HIV-1 RNA less than 200 copies per milliliter for 3 months or
      more were stratified by prior protease inhibitor (PI)- or non-nucleoside reverse
      transcriptase inhibitor (NNRTI)-based therapy and randomized (2:1) to EFV/FTC/TDF
      or to stay on their baseline regimen (SBR). Patient-reported measures were
      quality of life (QOL; SF-36 [version 2]), treatment adherence (visual analogue
      scale), preference of medication (POM), perceived ease of the regimen for
      condition (PERC), and a 20-item HIV symptom index. Overall, 203 subjects were
      randomized to EFV/FTC/TDF and 97 to SBR. Fifty-three percent of subjects had
      previously received a PI-based regimen; 47% an NNRTI-based therapy. Throughout
      the study, SF-36 summary scores did not differ significantly from baseline,
      regardless of previous ART or treatment allocation. Adherence was 96% or more in
      both groups at baseline and all subsequent study visits. At study conclusion, the
      EFV/FTC/TDF regimen was considered easier to follow than prior regimens by 97%
      and 96% of subjects previously receiving PI-based and NNRTI-based therapies,
      respectively. Overall, 91% of subjects switched to EFV/FTC/TDF indicated a
      preference over their prior therapy. Switching to EFV/FTC/TDF was associated with
      transient worsening/emergence of dizziness and sustained improvements in several
      other HIV-related symptoms. In conclusion, switching virologically suppressed,
      HIV-1-infected subjects from PI-based or NNRTI-based regimens to EFV/FTC/TDF was
      associated with maintained QOL and treatment adherence, and improved ease of use
      and treatment satisfaction.

PMID- 20156092
TI  - Recent FDA approvals and changes.

PMID- 20156094
TI  - We can do better: improving perinatal health in America.
AB  - The United States spends more on perinatal healthcare than any other nation, yet
      it consistently ranks near the bottom on most standard measures of perinatal
      health. This article examines how we can do better, based on the life course
      perspective and the ecological model. Collectively, these paradigms suggest the
      need for an expanded approach to improving perinatal health in America, one that
      emphasizes not only risk reduction during pregnancy but also health promotion and
      optimization across the life course. The approach needs to be both clinical and
      population based, addressing individual factors as well as social determinants.
      This article concludes with recommendations for increasing healthcare access,
      improving healthcare quality, investing in wellness, strengthening families and
      communities, and supporting research in perinatal health.

PMID- 20156095
TI  - Evaluation of HIV type 1 strains in men having sex with men and in female sex
      workers in Mombasa, Kenya.
AB  - We compared HIV-1 strains in incident and prevalent infections in a cohort of men
      having sex with men (MSM) and female sex workers (FSW) near Mombasa, Kenya and
      conducted a cross-sectional study of viral isolates from a sample of HIV-1
      infected MSM and FSW in Kilifi, Coast Province, Kenya. RNA extracted from plasma
      of 13 MSM, 9 FSW, and one heterosexual male was amplified by nested RT-PCR and
      the products were directly sequenced. HIV-1 strains from 21 individuals were
      characterized with one or more complete genome sequences, and two were sequenced
      in the Nef gene. The envelope quasispecies was also studied in one individual.
      Among MSM, eight strains were subtype A and five were recombinant. There were two
      epidemiologically linked pairs of sequences; one pair was subtype A and the other
      pair was a complex AA2CD recombinant of identical structure. Another MSM was
      dually infected with DG recombinant strains of related, but nonidentical,
      structure. MSM also harbored AC and AD recombinant strains. The FSW harbored
      seven subtype A strains, an AD recombinant, and an AA2D strain related to
      CRF16_A2D. The one heterosexual male studied had a subtype A infection. This MSM
      epidemic in Kenya appears to be of local origin, harboring many strains typical
      of the broader Kenyan epidemic. Characteristics of a close social network were
      identified, with extended chains of transmission, novel recombinant strains
      possibly generated within the network, and a relatively high proportion of
      recombinant and dual infections.

PMID- 20156096
TI  - Predictors of success with highly active antiretroviral therapy in an
      antiretroviral-naive urban population.
AB  - Abstract Predictors of successful virologic, immunologic, and clinical response
      with combined antiretroviral therapy (cART) containing a boosted protease
      inhibitor or a nonnucleoside reverse transcriptase inhibitor were analyzed among
      an antiretroviral naive (ARV-naive) urban cohort. Measures of success included
      virologic suppression [HIV-1 viral load (VL) <400 copies/ml], an increase in
      CD4(+) T cells from baseline of >100 cells/microl, and lack of development of an
      AIDS-defining illness at 24 and 48 weeks after cART initiation. Two hundred and
      eighty-seven ARV-naive patients were included in this cohort, of which 76.7% were
      male and 86.8% were nonwhite. At the time of cART initiation their median age was
      39 years, the geometric mean CD4(+) count was 42 cells/microl, and the mean viral
      load was 5.3 log(10) copies/ml. At 48 weeks, 72% of patients achieved virologic
      suppression, with > or =90% adherence and high school graduation predicting viral
      undetectability at 48 weeks. Baseline VL < or =100,000 copies/ml and a CD4(+)
      cell count >100 cells/microl were associated with viral suppression at 24 weeks
      [OR (95% CI) = 3.55 (1.29-9.81) and 3.96 (1.19-13.15), respectively]; female
      gender was associated with a greater increase in CD4(+) cell counts [OR (95% CI)
      = 7.41 (2.48-22.1)]. CDC stage A1-C2 at baseline predicted lack of clinical
      progression at 48 weeks. The results of this analysis of an ARV-naive cohort
      comprised predominantly of indigent, minority patients suggest that men who did
      not have a high school education and who had advanced HIV infection are less
      likely to have therapeutic success after cART initiation.

PMID- 20156097
TI  - Effectiveness of boosted protease inhibitor-based regimens in HIV type 1-infected
      patients who experienced virological failure with NNRTI-based antiretroviral
      therapy in a resource-limited setting.
AB  - A number of patients have experienced treatment failure while receiving non
      nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy
      (ART), particularly in resource-limited countries. The need remains for clinical
      data on protease inhibitor (PI)-based regimens in these patients. A retrospective
      cohort study was conducted among HIV-1-infected patients who had failed NNRTI
      based regimens, were naive to protease inhibitors (PIs), and subsequently
      initiated a salvage PI-based regimen between January 2004 and December 2006. The
      study period ended on 30 December 2007. One hundred and forty patients received a
      single-boosted PI +/- optimized background regimen (OBR) and 64 received double
      boosted PIs. The median (IQR) duration of follow-up was 19 (13-29) months. The
      overall virological failure rate at 24 months was 15.2%. No statistically
      significant difference was detected between the two regimen groups (single
      boosted PI +/- OBR 16.4% vs. double-boosted PIs 12.5%, log rank p = 0.818). At
      the end of the study, the median (IQR) change in CD4 cell counts for patients in
      the double-boosted PI group was higher than for patients in the single-boosted PI
      +/- OBR group [149 (53-322) vs. 105 (23-199), respectively, p = 0.012]. Patients
      receiving double-boosted PI regimens displayed a higher frequency of
      hypertriglyceridemia than those patients who received a single boosted PI +/- OBR
      (31% vs. 11%, respectively, p = 0.001). Boosted PI-based regimens showed
      acceptable virological outcomes among patients who had failed NNRTI-based ART. In
      the subgroup analysis, patients who received double-boosted PIs demonstrated a
      superior immunological response but not better virological outcomes compared to
      the single-boosted PI +/- OBR group.

PMID- 20156098
TI  - Peptide sugar mimetics prevent HIV type 1 replication in peripheral blood
      mononuclear cells in the presence of HIV-positive antiserum.
AB  - Cells of the immune system express a number of receptors that bind carbohydrate
      ligands. We questioned whether peptide mimetics of these ligands will activate
      phagocytic cells and thereby enhance an antiviral response. Short peptide
      sequences were identified by computational modeling of docking to glycan-specific
      lectins, selected as receptor analogs, and incorporated into quadravalent
      structures by peptide synthesis. A peptide with the sequence HPSLK bound to
      several lectins specific for monosaccharides and to lectins specific for Neu5Ac
      Gal-containing complex glycans, whereas a longer sequence, NPSHPLSG, bound only
      lectins specific for the more complex glycans. In cultures of peripheral blood
      mononuclear cells (PBMCs) these peptides stimulated phagocytosis of opsonized
      microspheres. The peptides inhibited replication of HIV-1 in PBMC cultures by 20
      80% at concentrations between 1 nM and 1 muM but inhibited replication 100% in
      the presence of diluted HIV-positive antiserum that alone inhibited replication
      by 30%. HPSLK caused about 50% loss of viability of cells at 1 mM, a
      concentration 10(6)-fold higher than an effective inhibitory concentration, but
      no toxicity was observed with NPSHPLSG. These results demonstrated that
      peptidomimetics of glycan ligands of cellular receptors are effective in
      activating phagocytosis, which may be a factor in providing complete inhibition
      of HIV-1 replication in vitro.

PMID- 20156099
TI  - Differential effects of P-class versus other CpG oligodeoxynucleotide classes on
      the impaired innate immunity of plasmacytoid dendritic cells in HIV type 1
      infection.
AB  - Abstract Human plasmacytoid dendritic cells (PDC) are the major producers of type
      I interferons (IFN) after stimulation with CpG oligodeoxynucleotides (ODN). HIV-1
      infected patients show a deficit in PDC numbers and function with progression of
      disease. CpG ODN appear to be attractive therapeutics to support the impaired
      innate immunity in HIV-1 infection. PDC counts, phenotype, and function were
      analyzed in 23 HIV-infected untreated individuals and 16 controls. Markers for
      migration (CCR7), activation (CD80), maturation (CD83), and endocytosis (BDCA2)
      were evaluated at baseline and 20 h after in vitro stimulation with class A, B,
      C, and P ODN. PDC counts and the expression of BDCA2 on these cells were
      significantly lower in HIV-1-infected subjects compared to controls (both p <
      0.001). After stimulation with CpG ODN, CD80 and CD83 were upregulated to a
      similar extent in patients and controls, whereas CCR7 was upregulated more
      efficiently by CpG-P and CpG-C than CpG-A in HIV-1-infected individuals compared
      to controls. The IFN-alpha induction significantly differed for the CpG ODN
      classes (A > P > C > B) in patients and controls (p < 0.05). Functional PDC
      deficits in IFN-alpha and TNF-alpha induction were particularly evident in
      subjects with less than 500 CD4(+) cells/mul. CpG-P ODNs not only induced
      remarkable IFN-alpha production in patient PBMCs, but also significantly
      upregulated the antibacterial and antiviral CXC chemokine IP-10. In conclusion,
      PDC counts, phenotype, and function are significantly impaired in HIV-1-infected
      subjects. Optimized P-class ODN may be effective in reversing this innate immune
      defect, which should be further evaluated in vivo.

PMID- 20156100
TI  - Genetic characterization of HIV type 1 Nef-induced vesicle secretion.
AB  - The HIV-1 Nef protein is known to be secreted, and our group has shown that Nef
      is secreted from nef-transfected and HIV-1-infected cells in small exosome-like
      vesicles (d. 40-100 nm). The role of secreted Nef remains to be fully
      characterized. Thus, it is important to characterize the nature of and the
      mechanisms regulating Nef secretion. We hypothesized that specific structural
      domains on the Nef protein interact with components of the endosomal trafficking
      machinery, sorting Nef into multivesicular bodies (MVB) and packaging it in
      exosome-like vesicles. To identify those domains, a series of mutants spanning
      the entire nef sequence were made and cloned into the expression vector pQB1,
      which expresses the mutants as Nef-GFP fusion proteins. These constructs were
      used in transient transfection assays to identify sequences necessary for
      secretion of the Nef-GFP fusion protein. N-terminal domains were identified as
      critical for Nef-induced vesicle secretion: (1) a basic cluster of four arginine
      residues (aa 17, 19, 21, 22), (2) the phosphofurin acidic cluster sequence (PACS;
      Glu62-65), and (3) a previously uncharacterized domain spanning amino acid
      residues 66-70 (VGFPV), which we named the secretion modification region (SMR).
      Additional amino acids P25, 29GVG31, and T44 were identified in HIV-1 Nef as
      regulating its secretion. These residues have not been associated with other
      reported Nef functions. The myristoylation domain, ubiquitination lysine
      residues, and the C-terminal portion of Nef (aa 71-206) had no effect on
      secretion. A minimal HIV-1 Nef sequence, comprising the identified motifs, was
      sufficient for Nef-induced vesicle secretion.

PMID- 20156101
TI  - Identification of rhesus macaque genital microbiota by 16S pyrosequencing shows
      similarities to human bacterial vaginosis: implications for use as an animal
      model for HIV vaginal infection.
AB  - The composition of the lower genital tract microbiota in women is believed to
      affect the risk of sexually acquiring HIV. Since macaque genital microbiota could
      similarly impact vaginal infection with SIV we identified microbiota in 11 rhesus
      macaques using multitag pyrosequencing of the 16S rRNA gene. The microbiota was
      polymicrobial with a median of nine distinct bacterial taxa per macaque (range 3
      16 taxa, each constituting 1% or more of the sequences). Taxa frequently found
      included Peptoniphilus, Sneathia, Porphyromonas, Mobiluncus, Atopobacter,
      Dialister, Thioreductor, Prevotella, and Streptococcus, many of which are also
      frequently found in women with bacterial vaginosis. Lactobacillus sequences
      (mostly L. johnsonii) were found in only four macaques but were not predominant
      in any (median of 0% of sequences, range 0-39%). All macaques were resampled 6
      months after the first time point to determine the stability of the microbiota.
      The microbiota remained polymicrobial with a median of 10 taxa (range 6-18).
      Microbial patterns remained similar for six of the macaques, changed
      substantially in two, and had a mixed pattern in three. Significant sialidase
      enzyme activity, a marker of bacteria vaginosis in women, was detected in genital
      fluid from 9/11 and 8/11 macaques from the first and second time points,
      respectively. These results show that the macaque lower genital microbiota
      resembled a bacteria vaginosis-type microbiota in women and suggest that the
      microbiota of macaques in captivity promote rather than protect against vaginal
      infection with SIV. These results also suggest macaques could be used as an
      animal model to study some aspects of bacterial vaginosis.

PMID- 20156102
TI  - CD4(+)CD25(+) T regulatory cells inhibit CD8(+) IFN-gamma production during acute
      and chronic FIV infection utilizing a membrane TGF-beta-dependent mechanism.
AB  - CD8(+) lymphocytes are critical to the control and elimination of viral
      pathogens. Impaired CD8(+) responses are well recognized in lentiviral
      infections; however, the mechanisms underlying CD8(+) impairment remain elusive.
      Using the feline immunodeficiency virus (FIV) model for human AIDS, we reported
      previously that CD4(+)CD25(+) Treg cells in both the acute and long-term,
      asymptomatic phase of infection are constitutively activated and suppress
      CD4(+)CD25(-) T cell responses. In the current study, we have demonstrated that
      CD4(+)CD25(+) Treg cells suppress CD8(+) responses to immune stimulation during
      both the acute and chronic, asymptomatic phase of FIV infection and that the
      mechanism of suppression may be mediated by membrane-associated TGF-beta (mTGF
      beta) on CD4(+)CD25(+) lymphocytes. Depletion of CD4(+)CD25(+) lymphocytes from
      lymph node suspensions significantly enhanced production of IFN-gamma during the
      acute phase of infection and coculture of CD8(+) lymphocytes with CD4(+)CD25(+)
      lymphocytes resulted in suppression of CD8(+) IFN-gamma during both the acute and
      chronic stages of infection. FACS analysis indicated that there was TGF-betaRII
      upregulation on CD8(+) cells from FIV(+) cats during the acute and chronic stage
      of infection. In addition, there was upregulation of mTGF-beta on the
      CD4(+)CD25(+) subset in chronically infected cats. In support of activation of
      the TGF-beta signaling pathway, Western blotting showed Smad 2 phosphorylation in
      CD8(+) targets following CD4(+)CD25(+)/CD8(+) coculture. These results
      demonstrate the suppressive effect CD4(+)CD25(+) Treg cells have on the CD8(+)
      immune response during the acute and chronic stages of FIV infection and suggest
      that the mechanism of suppression may be mediated by mTGF-beta.

PMID- 20156104
TI  - Genotypic characterization of HIV type 1 env gp160 sequences from three regions
      in Thailand.
AB  - We report 25 env gp160 sequences from patients in three geographically distinct
      districts of Thailand, i.e., Lampang in the north, Trang in the south and Rayong
      in the east. One of these is a CRF01_AE/subtype B recombinant and the other 24
      sequences are purely CRF01_AE. Very little interpopulation diversity was observed
      between the sequences from the three different geographic regions and from those
      previously reported by our laboratory from central Thailand. Potential N-linked
      glycosylation sites (PNLGs) were reasonably conserved among the 25 sequences: we
      found 15 highly conserved PNLGs on gp120 and 4 almost fully conserved PNLGs on
      gp41. Analysis of coreceptor tropism revealed that six of the isolates were dual
      tropic and the others were R5 tropic. We also examined a rare seven amino acid
      deletion found in one isolate at position 847-853 on gp41. These results may
      enhance our understanding of HIV-1 currently circulating in Thailand.

PMID- 20156103
TI  - Comparison of genotypic resistance mutations in treatment-naive HIV type 1
      infected patients in Korea and China.
AB  - Seventy-six treatment-naive human immunodeficiency virus (HIV)-1-infected
      patients were recruited from Korea and China to evaluate transmitted drug
      resistance (TDR). Although no major TDR was observed within the study population,
      some resistance-associated mutations in the reverse transcriptase region were
      observed (V118I 9.2%, V179D 7.9%). The frequencies of resistance-associated
      mutations in NNRTI (V179D) and PI minor mutations were higher in Korean patients
      compared with Chinese patients (13.6% vs. 0%, 45.5% vs. 12.5%, p < 0.05).
      Although unique clustering was observed in phylogenetic analyses according to
      geographic sources, cautious monitoring is recommended due to increasing TDR
      reports in this area where the population shares close geographic and cultural
      aspects.

PMID- 20156105
TI  - Prevalence of primary drug resistance-associated mutations among HIV type 1
      vertically Infected children in Belo Horizonte, Brazil.
AB  - In the past few years there has been increasing concern about the transmission of
      drug-resistant HIV. This study aimed to describe the frequency of primary
      mutations associated with HIV-1 drug resistance and the prevalence of genetic HIV
      subtypes in a population of vertically infected children before the initiation of
      HAART. At the time of genotypic testing, the median age was 6.0 years (IQR 25
      75%: 3.8-9.2) and the median age at admission was 3.84 years (IQR 25-75%: 1.23
      6.11). Antepartum maternal ARV exposure for PMTCT occurred for three (7.3%)
      mothers. According to the WHO criteria, primary ARV resistance mutations were
      detected in four out of 41 (9.8%) children. Subtype B was the most prevalent
      (63.4%). The relatively high prevalence of primary HIV-1 DRMs in this cohort of
      perinatally infected children in Brazil supports the local recommendation to
      perform resistance testing in all newly diagnosed children, regardless of age at
      diagnosis and antenatal ARV exposure.

PMID- 20156107
TI  - HIV type 1 B'/C recombinant (CRF07_BC) in virologic noncontrollers elicits
      neutralizing antibodies against heterologous but not autologous viruses.

PMID- 20156106
TI  - Characterization of HIV type 1 genotypes and drug resistance mutations among drug
      naive HIV type 1-infected patients in Northern Vietnam.
AB  - To evaluate HIV-1 drug resistance-associated mutations among drug-naive HIV-1
      infected patients in Northern Vietnam, we performed sequence analysis of HIV-1
      pol-PR and pol-RT in samples collected from 206 (161 men and 45 women) consenting
      patients in 2008. From these 206 samples, we successfully sequenced 173 pol-PR
      and 155 pol-RT genes. Phylogenetic analysis revealed that all patients were
      infected with HIV-1 CRF01_AE. Major protease inhibitor resistance mutations, such
      as L33F, M46I, and M46L, were found in three patients (1.7%). Major reverse
      transcriptase inhibitor (RTI) resistance mutations were found in seven patients
      (4.5%), four of whom had single mutations: A62V (nucleoside RTI resistance
      mutation) in two cases and K103N and Y181C (nonnucleoside RTI resistance
      mutation) in one case each. Three patients had multiple RTI resistance mutations:
      two, three, and seven, respectively. Thus, monitoring for drug-resistant HIV-1
      and performing drug resistance testing before initiating antiretroviral therapy
      (ART) are recommended to facilitate selection of the appropriate ART and better
      clinical outcomes in Vietnam.

PMID- 20156108
TI  - Pediatric HIV BioBank: a new role of the Spanish HIV BioBank in pediatric HIV
      research.
AB  - The vulnerability of children has long raised ethical concerns resulting in the
      lack of inclusion of children in research studies. This has impeded the
      development of relevant medical therapies specific for children. In response to
      these circumstances, international policies have begun to recognize the need to
      carry out research focused on children. Translational HIV infection research is
      highly dependent on many factors including the availability, quality, and
      traceability of samples and their associated data under a strict system of
      quality management. The primary objective of the Pediatric HIV BioBank is to
      contribute to the furthering of scientific knowledge about vertical HIV
      infection. To achieve this aim, the BioBank processes, stores, and provides
      distinct samples from HIV/AIDS children to research projects free of charge.
      Strict compliance to ethical norms is always guaranteed. At present the Pediatric
      HIV BioBank has 429 vials containing different sample types from 243 vertically
      HIV-infected children. The Pediatric HIV BioBank represents a novel approach to
      HIV research that might be of general interest not only for basic and clinical
      research teams working with HIV, but also for those groups trying to establish
      large networks focused on researching specific clinical problems. It also
      represents a model to stimulate cooperative research on specific clinical
      problems. The main objective of this article is to show the structure and
      function of the Pediatric HIV BioBank that allow it to efficiently provide
      samples to different research projects in Spain and in other countries.

PMID- 20156109
TI  - Predictive value of HIV type 1 DNA levels on overall survival in HIV-related
      lymphoma Patients treated with high-dose chemotherapy (HDC) plus autologous stem
      cell transplantation (ASCT).
AB  - The kinetics and predictive value of HIV-1 DNA (HIV DNA) levels in relapsed or
      refractory HIV lymphoma patients, treated with high-dose chemotherapy (HDC)
      followed by autologous stem cell transplantation (ASCT), were investigated. HIV
      DNA was measured by real-time PCR in the peripheral blood mononuclear cells
      (PBMCs) of 22 patients observed for a median follow-up of 31.0 months. At
      baseline, HIV DNA was found to be correlated with HIV-1 RNA (HIV RNA) (r = 0.56),
      but not with CD4(+) counts (r = -0.10). HIV RNA load was under control for the
      entire follow-up, while HIV DNA levels were almost always detectable (baseline
      levels vs. 1 year from ASCT levels, p > 0.05). Baseline HIV DNA levels were
      significantly different between alive and deceased patients (p = 0.03), and the
      overall survival (OS) analysis showed that for patients with higher HIV DNA
      levels at baseline there was a higher and nearly significant risk of death if
      compared to patients with lower levels (HR, 8.33, 95% CI, 0.99-70.06, p = 0.05).
      Our study demonstrated that high HIV DNA levels at baseline could predict overall
      survival after ASCT in one of the largest cohorts of HIV lymphoma patients
      treated with salvage therapy.

PMID- 20156110
TI  - Detection, treatment, and referral of perinatal depression and anxiety by
      obstetrical providers.
AB  - AIMS: This study aimed to assess the rates of detection, treatment, and referral
      of maternal depression and anxiety by obstetrical providers during pregnancy and
      at 6 weeks postpartum. METHODS: A convenience sample of women receiving
      obstetrical care at a large urban teaching hospital (n = 491) was screened for
      depression and anxiety during the third trimester of pregnancy and again at 6
      weeks postpartum using the Edinburgh Postnatal Depression Scale and the anxiety
      portions of the Patient Health Questionnaire. Participants were also asked if
      they thought they needed help for depression, anxiety, or stress at the two time
      points. Obstetrical providers were blind to screening results. Two months
      postdelivery, each woman's obstetrical electronic medical record (EMR) was
      reviewed for documentation of psychiatric symptoms, diagnoses, psychiatric
      treatment, and mental health referrals at the two time points. Data were analyzed
      using descriptive statistics. RESULTS: Twenty-three percent of participants
      screened positive for an anxiety disorder or high levels of depressive symptoms
      or both prenatally, and 17% screened positive at 6 weeks postpartum. The majority
      of women who screened positive were not identified by their providers during
      pregnancy or postpartum. Only 15% of positively screened participants had
      evidence of any mental health treatment in their EMR during pregnancy, with
      equally low rates of referral to mental health or social services. In the
      postpartum period, only 25% of positively screened postpartum women received
      treatment, and an additional 2.5% were referred. A low proportion of women who
      reported they felt a need for help with depression, anxiety, or stress prenatally
      or postpartum received treatment or referral. CONCLUSIONS: These findings
      indicate that detection, treatment, and referral of perinatal depression by
      obstetrical providers are seriously lacking and need to be addressed.

PMID- 20156112
TI  - Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal
      tissue engineering.
AB  - The goal of this study was the production of a decellularized kidney scaffold
      with structural, mechanical, and physiological properties necessary for
      engineering basic renal structures in vitro. Fetal, infant, juvenile, and adult
      rhesus monkey kidney sections were treated with either 1% (v/v) sodium dodecyl
      sulfate or Triton X-100 followed by quantitative and qualitative analysis.
      Comparison of decellularization agents and incubation temperatures demonstrated
      sodium dodecyl sulfate at 4 degrees C to be most effective in preserving the
      native architecture. Hematoxylin and eosin staining confirmed the removal of
      cellular material, and immunohistochemistry demonstrated preservation of native
      expression patterns of extracellular matrix proteins, including heparan sulfate
      proteoglycan, fibronectin, collagen types I and IV, and laminin. Biomechanical
      testing revealed a decrease in the compressive modulus of decellularized compared
      to fresh kidneys. Layering of fetal kidney explants on age-matched decellularized
      kidney scaffolds demonstrated the capacity of the scaffold to support
      Pax2+/vimentin+ cell attachment and migration to recellularize the scaffold.
      These findings demonstrate that decellularized kidney sections retain critical
      structural and functional properties necessary for use as a three-dimensional
      scaffold and promote cellular repopulation. Further, this study provides the
      initial steps in developing new regenerative medicine strategies for renal tissue
      engineering and repair.

PMID- 20156113
TI  - Concurrent maternal and fetal ovarian cysts.
AB  - Due to improvements in ultrasonography, the detection of fetal abdominal masses
      has increased. We describe a case of co-existing maternal and fetal ovarian cysts
      in a 37-year-old primiparous woman. The fetal ovarian cyst was first identified
      in the third trimester and reached a maximum diameter of 9 cm. The maternal cysts
      were present from 20 weeks onwards; with a maximum diameter of 8 cm. Histological
      examination showed the maternal lesions were benign dermoid cysts. The fetal
      lesion resolved spontaneously by 5 months. This case illustrates that fetal and
      maternal ovarian cysts may co-exist and could potentially have a similar hormonal
      etiology.

PMID- 20156114
TI  - Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis
      inhibitor bevacizumab in cancer patients: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: The risk of cardiovascular toxicities is a serious concern with the
      increased application of angiogenesis inhibitors in current cancer therapy.
      Arterial thromboembolic events (ATE) were associated with bevacizumab, an
      antibody against vascular endothelial growth factor. To determine the risk of ATE
      including cardiac ischemia and stroke, a systematic review and meta-analysis of
      published randomized controlled trials (RCTs) was performed. METHODS: We searched
      the databases of PubMed, Web of Science, and American Society of Clinical
      Oncology conferences to identify relevant clinical trials up to May, 2009.
      Eligible studies included prospective RCTs in which bevacizumab was compared to a
      control concurrently in combination with standard anti-neoplastic therapy.
      Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs)
      were calculated using random-effects or fixed-effects models. RESULTS: A total of
      12 617 patients with a variety of advanced solid tumors from 20 RCTs were
      included for analysis. The incidences of all-grade and high-grade ATE in patients
      receiving bevacizumab were 3.3% (95% CI, 2.0-5.6%) and 2.0% (95% CI, 1.7-2.5)
      respectively. Patients treated with bevacizumab had a significantly increased
      risk of ATE with an RR of 1.44 (95% CI, 1.08-1.91; p=0.013) compared with
      controls. The risk similarly increased for bevacizumab at 2.5 and 5 mg/kg/week;
      in addition, significantly increased risks were observed in patients with renal
      cell cancer (RR, 3.72, 95% CI, 1.15-12.04; p=0.029) and colorectal cancer (RR,
      1.89, 95% CI, 1.28-2.80, p=0.001). Notably, the risk of high-grade cardiac
      ischemia with bevacizumab was significantly higher than controls with an RR of
      2.14 (95% CI, 1.12-4.08, p=0.021); however, the risk of ischemic stroke with
      bevacizumab was not significantly different from controls (RR, 1.37, 95% CI, 0.67
      2.79, p=0.39). DISCUSSION: Treatment with bevacizumab may significantly increase
      the risk of cardiac ischemic events in cancer patients.

PMID- 20156115
TI  - Breast cancer recurrence risk related to concurrent use of SSRI antidepressants
      and tamoxifen.
AB  - BACKGROUND: Up to one-quarter of breast cancer patients suffer clinically
      significant depression in the year after diagnosis, which may respond to
      intervention. About half may be prescribed a psychotropic medication, such as a
      selective serotonin reuptake inhibitor (SSRI), while completing breast cancer
      therapy. Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also metabolizes
      tamoxifen to more active forms. Therefore, concurrent use of SSRIs may reduce
      tamoxifen's effectiveness at preventing breast cancer recurrence. The SSRI
      citalopram has limited potency to inhibit CYP2D6 activity, so has been
      recommended for breast cancer patients taking tamoxifen. This study provides
      epidemiologic evidence to support this recommendation. MATERIAL AND METHODS: We
      conducted a case-control study of breast cancer recurrence nested in the
      population of female residents of Denmark who were diagnosed with non-metastatic
      estrogen-receptor positive breast cancers between 1994 and 2001 and who took
      tamoxifen for at least one year. We ascertained complete prescription histories
      by linking cases' and controls' civil registration numbers to the Danish national
      prescription registry. We estimated the association between SSRI use while taking
      tamoxifen and risk of recurrent breast cancer. RESULTS: About the same proportion
      of recurrent cases (37 of 366) and matched controls (35 of 366) received at least
      one prescription for citalopram or its s-stereoisomer while taking tamoxifen
      (adjusted odds ratio = 1.1, 95% confidence interval = 0.7, 1.7). Breast cancer
      patients taking other SSRIs were also at no increased risk of recurrence
      (adjusted odds ratio = 0.9, 95% confidence interval = 0.5, 1.8). DISCUSSION:
      Breast cancer patients with indications for an SSRI may be prescribed citalopram 
      and possibly other SSRI - without adversely affecting the outcome of adjuvant
      therapy with tamoxifen.

PMID- 20156111
TI  - Friedreich ataxia: molecular mechanisms, redox considerations, and therapeutic
      opportunities.
AB  - Mitochondrial dysfunction and oxidative damage are at the origin of numerous
      neurodegenerative diseases like Friedreich ataxia and Alzheimer and Parkinson
      diseases. Friedreich ataxia (FRDA) is the most common hereditary ataxia, with one
      individual affected in 50,000. This disease is characterized by progressive
      degeneration of the central and peripheral nervous systems, cardiomyopathy, and
      increased incidence of diabetes mellitus. FRDA is caused by a dynamic mutation, a
      GAA trinucleotide repeat expansion, in the first intron of the FXN gene. Fewer
      than 5% of the patients are heterozygous and carry point mutations in the other
      allele. The molecular consequences of the GAA triplet expansion is transcription
      silencing and reduced expression of the encoded mitochondrial protein, frataxin.
      The precise cellular role of frataxin is not known; however, it is clear now that
      several mitochondrial functions are not performed correctly in patient cells. The
      affected functions include respiration, iron-sulfur cluster assembly, iron
      homeostasis, and maintenance of the redox status. This review highlights the
      molecular mechanisms that underlie the disease phenotypes and the different
      hypothesis about the function of frataxin. In addition, we present an overview of
      the most recent therapeutic approaches for this severe disease that actually has
      no efficient treatment.

PMID- 20156117
TI  - Preferences of caregiver when experiencing nausea and vomiting during pregnancy.
AB  - AIM: To assess the preferences of pregnant women regarding the type of assistance
      desired to alleviate the consequences of nausea and vomiting of pregnancy (NVP).
      METHODS: Women with NVP were asked to complete an online survey of 12 questions
      assessing the extent of NVP and the perspective on the importance of different
      healthcare professionals for their improvement. RESULTS: A total of 121 pregnant
      women completed the survey. The median maternal age was 29 years and the average
      gestational age was 12.4+/-7.6 weeks. Sixty-four of the women (52.9%) had NVP in
      their previous pregnancy, which resulted in an average of 14.6+/-21.1 lost days
      of paid work. NVP necessitated admission to the emergency room in 36 (29.7%).
      When asked to rate (max 4 points) which healthcare professional would provide the
      best assistance for NVP, the physician was rated as the most important (average
      score of 3.56/4), followed by dietician (3.40/4), nurse (3.05/4) and social
      worker/psychologist as least important (1.77/4). CONCLUSION: Our findings
      illustrate women's perspective on NVP. According to our online survey, women
      perceive medically- and nutritionally-based care as most useful, whereas
      psychosocial factors are perceived to be less useful despite playing a central
      role in NVP.

PMID- 20156116
TI  - Trends in the survival of patients diagnosed with kidney or urinary bladder
      cancer in the Nordic countries 1964-2003 followed up to the end of 2006.
AB  - BACKGROUND: Previous studies have shown systematic differences between the Nordic
      Countries in population-based relative survival following a kidney or urinary
      bladder cancer diagnosis. Comparison of bladder cancer over time and between
      Nordic registries is complicated by variable coding practices with respect to the
      inclusion of in situ cases with invasive tumours. MATERIAL AND METHODS: Five-year
      relative survival of patients with urinary cancer diagnosed in the Nordic
      countries 1964-2003 and followed up for death through 2006 was studied and
      contrasted with developments in incidence and mortality. RESULTS: The survival
      following bladder cancer was higher than for kidney cancer and highest for men.
      Survival increased over the years in all countries, more for kidney cancer than
      bladder cancer. For Danish kidney cancer patients, the rate of increase over all
      the years has been lower than in the other countries, especially among women,
      resulting in a survival in Denmark some 10-20% points lower than elsewhere in
      1999-2003. Danish bladder cancer patient survival was in the last period 4%
      points lower among men and 10% points lower among women than in the other Nordic
      countries. The differences were mainly found in the first year following
      diagnosis, where a higher excess mortality in Denmark was observed. Survival
      decreased with higher age at diagnosis. CONCLUSION: The increasing 5-year
      relative survival in all the Nordic countries for both kidney and bladder cancer
      are promising, but for kidney cancer a higher percentage detected coincidentally
      during an imaging investigation for other diseases could play a role. Denmark had
      the lowest survival, despite their known practice of including benign conditions
      with invasive bladder cancers. The lower Danish survival after kidney and bladder
      cancer in the first year after diagnosis could be due to later diagnosis on
      average, a higher co-morbidity from smoking-related diseases, and perhaps, less
      adequate cancer treatment and management in Denmark.

PMID- 20156118
TI  - Unequal but monozygous: a history of twin-twin transfusion syndrome.
AB  - Twin-twin transfusion is the major cause of mortality and morbidity in
      monochorionic twins. Its pathogenesis has been gradually elucidated over the last
      three centuries. Among obstetricians, there was a long-lasting controversy on the
      existence of placental anastomoses and whether or not to tie the placental end of
      the firstborn infant's cord. However, a twin pregnancy practically never could be
      excluded. Stalpart van der Wiel described a twin-twin vessel connection in 1687.
      Studies on interfetal anastomoses using injection of placental vessels were
      published by Smellie in 1752, Osiander in 1781, and Brachet in 1821. Different
      types of anastomoses, and their associated fetal disorders were classified by
      Schatz in a series of papers at the end of the 19(th) century. With the advent of
      ultrasound and laser techniques, prenatal diagnosis and treatment became
      available in the last decade of the 20(th) century.

PMID- 20156119
TI  - Biological characterization of ADAM22 variants reveals the importance of a
      disintegrin domain sequence in cell surface expression.
AB  - ADAM metallopeptidase domain 22 (ADAM22) is a neuronal membrane-spanning protein
      that is a potential receptor for leucine-rich, glioma-inactivated 1 (LGI1), and
      leucine-rich repeat LGI family, member 4 (LGI4). Several lines of study have
      shown a direct interaction between ADAM22 and LGI1, a mutation which is
      responsible for inherited epilepsy in humans. Both ADAM22-deficient mice and claw
      paw mice, congenitally deficient in LGI4, show hypomyelination in the peripheral
      nerves, suggesting that these molecules are involved in myelination processes.
      These findings mark ADAM22 as a potential target molecule for epilepsy or
      demyelination diseases. To investigate the relationship between ADAM22 mutation
      and its biological character, we designed and examined several ADAM22 variants.
      We discovered that the ADAM22 P81R variant, the most common polymorphic
      variation, works as well as the wild-type ADAM22. We also showed that mutations
      in the disintegrin domain cause a marked decrease in the processing of ADAM22
      preproteins, and result in reduced LGI4-binding abilities. Our findings provide
      valuable information for mutation screening of the ADAM22 gene in patients
      suffering from epilepsy or demyelinating diseases.

PMID- 20156120
TI  - Conservative management of mesh-site infection in hernia repair.
AB  - BACKGROUND: Mesh hernioplasty is the preferred surgical procedure for large
      abdominal wall hernias. Infection remains one of the most challenging
      complications of this operation. Salvaging infected prosthetic material after
      ventral hernia repair is rarely successful. Most cases require mesh excision and
      complex abdominal wall reconstruction, with variable success rates. In this
      article, we report 3 cases of mesh salvage after laparoscopic ventral
      herniorrhapy with a novel use of percutaneous drainage and antibiotic irrigation.
      RESULTS: Three patients developed infected seromas after laparoscopic ventral
      hernia repair. The fascial defect of the first patient was repaired with a
      commercially available 20 x 18 cm polytetrafluoroethylene (PTFE) mesh. A complex
      fluid collection developed the following month in the anterior abdominal wall
      overlying the patient's mesh. The cultures grew Staphylococcus aureus. The second
      patient had a 30 x 20 cm PTFE mesh placed, which developed a fluid collection
      with Enterococcus faecalis and Escherichia coli. The third case underwent repair,
      using a another commercially available 22 x 28 cm PTFE mesh. A fluid collection
      measuring 20 x 10 cm in the anterior abdominal wall developed, growing
      Staphylococcus lugdunensis. In all 3 cases, a percutaneous drain was placed
      within the fluid collection and long-term intravenous (i.v.) access was obtained.
      I.v. antibiotics were initiated. In addition, gentamicin (80 mg) with 20 mL of
      saline was infused through the drain 3 times a day. All patients have remained
      free of clinical signs of infection following the completion of therapy.
      CONCLUSIONS: Infected mesh after laparoscopic ventral herniorrhapy without
      systemic sepsis may be amenable to nonoperative treatment. A conservative
      approach that includes percutaneous drainage followed by antibiotic irrigation is
      a potential alternative to prosthetic removal in carefully selected patients.
      Further evaluation of this technique is warranted to define the most appropriate
      management strategies for these patients.

PMID- 20156121
TI  - Pneumoscrotum due to perforated peptic ulcer previously sutured by laparoscopy.
AB  - Pneumoscrotum is a rare condition defined by the presence of gas within the
      scrotum. Most cases are associated with the pneumoperitoneum; the condition has
      been described after various diagnostic and therapeutic procedures and disease
      conditions. In this article, we report a case of a patient admitted to the
      emergency department for right-upper quadrant abdominal pain. Abdominal X-ray
      showed free air in the right subdiaphragm; computed tomography (CT) confirmed
      free air in the abdomen and detected free fluid in the pelvis. The patient
      underwent laparoscopy, at which time a 1-cm perforation on the anterior wall of
      the gastric antrum near the pylorus was identified. The perforation was sutured
      with three detached stitches of reabsorbable material. Approximately 2 days after
      the surgical procedure, physical examination of the patient showed significant
      scrotal swelling suspicious for the presence of subcutaneous air. A CT scan
      confirmed the presence of the pneumoscrotum. The patient returned to the
      operating room and underwent an exploratory laparotomy. A new perforation was
      identified beneath the previous one and was sutured with two detached stitches.
      The patient was discharged uneventfully after 8 days of hospitalization.
      Pneumoscrotum should be recognized as an early sign of recurrence in patients
      operated on laparoscopically for peptic ulcer.

PMID- 20156122
TI  - The British-flag technique of mesh insertion in transabdominal preperitonial
      laparoscopic inguinal hernia repair.
AB  - Imaging of early postoperative complications after mesh repair has shown
      "foldings" of the prosthetic mesh, leading to displacement and associated hernia
      recurrence. A rectangular two-dimensional mesh introduced into the abdomen and
      fitted into a concave three-dimensional cavity does not lie evenly and is
      susceptible to crumpling. Hence, we propose to introduce a geometrically
      corrected mesh design that would allow easier placement and compliment the
      anatomic shape of the abdominal cavity.

PMID- 20156123
TI  - Technical challenges in laparoscopic cholecystectomy in situs inversus.
AB  - Laparoscopic cholecystectomy in patients with situs inversus can be a technically
      challenging procedure. Although laparoscopic cholecystectomy has been described
      in patients with situs inversus, no standard technique has been described. We are
      presenting our experience of laparoscopic cholecystectomy in two patients with
      situs inversus and discuss the problems encountered during surgery and likely
      remedies.

PMID- 20156124
TI  - Metabolic supplementation with enhanced external counterpulsation improves
      myocardial function in acquired cardiomyopathy: a case report.
AB  - BACKGROUND: Cardiomyopathy is reflected in a deterioration of heart function,
      increased risk of developing arrhythmias, and the potential for sudden cardiac
      death. The use of enhanced external counterpulsation has been recommended for
      treating chronic stable angina in high-risk surgical patients. Furthermore, cells
      require adequate levels of adenosine triphosphate for the maintenance of
      integrity and function. Lower myocardial levels of adenosine triphosphate are
      commonly found with ischemia and heart failure. d-Ribose, a natural occurring
      carbohydrate, enhances the regeneration of adenosine triphosphate levels and
      improves diastolic function following ischemia. SUBJECT: We present a patient
      with cardiomyopathy and marked reduced cardiac function. CONCLUSIONS: This
      patient underwent enhanced external counterpulsation and metabolic
      supplementation, including d-ribose, and achieved a significant functional
      improvement.

PMID- 20156125
TI  - Telemedicine can make healthcare greener.
AB  - The American healthcare industry is generally lacking environmentally sustainable
      practices. The environmental impact of healthcare practices in the country has
      been largely disregarded due to ambivalence, ignorance, and fears of additional
      costs and regulations. The current practices continue to pollute the environment
      by requiring large amounts of travel and paperwork by both the patient and the
      clinician. Telemedicine and health information technology help save time, energy,
      raw materials (such as paper and plastic), and fuel, thereby lowering the carbon
      footprint of the health industry. By implementing green practices, for instance,
      by engaging in carbon credit programs, the health industry could benefit
      financially as well as reduce its negative impact on the health of our planet.
      Companies that reduce their carbon emissions by implementing energy-saving
      practices can sell their carbon credits to companies that emit more carbon than
      permissible by their legally binding commitment. These carbon profits can then be
      used for healthcare research or to provide healthcare to the underserved.
      Alternatively, the savings could be used for green purchasing and to implement
      other carbon-reducing activities. This report reviews the numerous possible
      options for the American health industry to become greener and lower its carbon
      footprint while at the same time becoming more time- and cost efficient.

PMID- 20156127
TI  - Does online health information seeking act like a health behavior?: a test of the
      behavioral model.
AB  - OBJECTIVE: This analysis tests the hypothesis that health information search can
      be modeled using the behavioral model, a tool traditionally used for other
      healthcare behaviors. MATERIALS AND METHODS: The Pew Internet and American Life
      August 2006 Survey was used to model five selected Internet health information
      seeking behaviors: information on a specific disease, diet and nutrition, mental
      health, complementary and alternative medicine, and sexual health. Each behavior
      was modeled using hierarchical logistic regression with independent variables of
      predisposing factors (age, race, sex, and education), enabling factors (home
      Internet access, Internet experience, and high-speed access), and need factors
      (health status, chronic health condition, and current health crisis). RESULTS:
      Health information search is not a monolithic behavior. Sex, age over 65, current
      health crisis, and regular use of the Internet were the most consistent
      predictors of use, each being significant in four of the five models. Blacks
      (odds ratio [OR] = 0.50, 95% confidence interval [CI] 0.34-0.74) and Hispanics
      (OR = 0.59, 95% CI 0.37-0.95) were significantly less likely than whites to
      search for information on a specific disease or condition but blacks (OR = 2.73,
      95% CI 1.69-4.43) were more likely than whites to search for sexual health
      information and Hispanics (OR = 1.72, 95% CI 1.09-2.73) were more likely than
      whites to search for complementary and alternative medicine information. Pseudo
      r(2) for the fully specified models ranged from 0.13 for mental health search to
      0.32 for specific disease search. CONCLUSION: Health Internet behaviors can
      successfully be described using models designed for traditional health behaviors;
      however, different health information seeking behaviors have different user
      profiles.

PMID- 20156128
TI  - Use of mobile phones as a tool for United States health diplomacy abroad.
AB  - Rapidly emerging mobile communications platforms, such as mobile phones, in
      countries across Africa, Iraq, and Afghanistan offer new opportunities for direct
      public engagement in health systems, placing tools and timely information into
      the hands of those who need it most. Early results from pioneering work suggest
      real benefits of mobile devices in addressing access to care, monitoring and
      treating diseases, and providing continuous medical education and training. The
      Military Health System, a $43-billion global healthcare system within the U.S.
      Department of Defense, in partnership with other U.S. government agencies and
      nongovernmental organizations and the international health sector, can make
      valuable contributions to creating a sustainable global m-health infrastructure.

PMID- 20156129
TI  - Lifestyle factors, hormonal contraception, and premenstrual symptoms: the United
      Kingdom Southampton Women's Survey.
AB  - OBJECTIVE: To estimate the prevalence of premenstrual symptoms in women from the
      general population in Southampton, U.K., and examine their association with
      lifestyle factors and contraceptive use. METHODS: This was a cross-sectional
      survey in the city of Southampton, U.K., of 974 women aged 20-34 years (53% of
      the 1841 women invited to participate). The survey consisted of interviews,
      questionnaires, and completion of a prospective 6-week menstrual symptom diary
      recording on a daily basis the presence and severity of 11 common premenstrual
      symptoms. Premenstrual symptoms were identified from the diaries by two
      clinicians who reviewed them independently using a predefined algorithm to assess
      the onset and decline of symptoms in relation to the start of menstruation.
      RESULTS: Of the women surveyed, 24% were considered to have premenstrual symptoms
      (95% confidence interval [CI] 21-27). Women were less likely to have symptoms if
      they had higher levels of educational attainment and suffered less from stress.
      No associations were found between premenstrual symptoms and diet, alcohol, or
      strenuous exercise nor after adjustment for other factors, with age, smoking, or
      body mass index (BMI). Use of any form of hormonal contraceptives was associated
      with a lower prevalence of premenstrual symptoms (prevalence ratio 0.66, 95% CI
      0.52-0.84). CONCLUSIONS: Premenstrual symptoms were common in this cohort. Use of
      hormonal contraceptive methods was associated with a lower prevalence of these
      symptoms.

PMID- 20156130
TI  - Minority women victims of recent sexual violence: disparities in incident
      history.
AB  - AIMS: The aims of this descriptive study were to (1) describe assault and care
      characteristics and (2) determine differences in assault and care characteristics
      between black women and white women who sought emergency care following sexual
      violence. METHODS: A retrospective, cross-sectional design was used to examine
      forensic examination data characterizing the incident history reported by women
      victims of sexual violence at the time of a forensic nurse examination.
      Examinations occurred at an urban university-affiliated hospital emergency
      department (ED) over a 2-year period. RESULTS: Of the women (n = 173) seeking
      care in the ED, 58.4% were black and 41.6% were white. When compared with white
      women, black women were more likely to have weapons used in their assaults (42.6%
      vs. 16.7%, p < 0.00) and to be assaulted in the city rather than the suburbs
      (82.8% vs. 56.5%, p < 0.00). In general, substance use prior to the assault was
      reported to have occurred in 49.1% of the victims and 41% of the assailants;
      however, differences existed in the type and pattern of substance use by
      race/ethnicity. Black victims were more likely to report use of illicit drugs
      (28.7% vs. 12.5%, p = 0.01). White women were more likely than black women to
      report personal alcohol use prior to their assault, with significant differences
      for drinking by victims (47.2% vs. 23.8%, p = 0.01) or assailant use of alcohol
      (47.2% vs. 23.8%, p = 0.00). White women were more likely than black women to
      report both they and the assailant had used some type of substance (38.9 vs.
      21.8, p = 0.01). Black women were more likely to arrive to the ED via EMS
      services (45.5% vs. 29.2%, p = 0.03). There were no reported differences in care
      characteristics by race. CONCLUSIONS: Findings from this study suggest that
      differences exist in assault characteristics between black and white women. Use
      of substances, including alcohol, plays an important role in sexual violence in
      women and should be a focus of preventive intervention initiatives when
      conducting a forensic examination. Both coordinated responses and comprehensive,
      individualized care by specially trained providers are important in the emergency
      care of minority women who are victims of recent sexual violence.

PMID- 20156131
TI  - Identification of ovarian cancer symptoms in health insurance claims data.
AB  - BACKGROUND: Women with ovarian cancer have reported abdominal/pelvic pain,
      bloating, difficulty eating or feeling full quickly, and urinary
      frequency/urgency prior to diagnosis. We explored these findings in a general
      population using a dataset of insured women aged 40-64 and investigated the
      potential effectiveness of a routine review of claims data as a prescreen to
      identify women at high risk for ovarian cancer. METHODS: Data from a large
      Washington State health insurer were merged with the Seattle-Puget Sound
      Surveillance, Epidemiology and End Results (SEER) cancer registry for 2000-2004.
      We estimated the prevalence of symptoms in the 36 months prior to diagnosis for
      early and late-stage ovarian cancer cases and for two comparison groups. The
      potential performance of a passive screener that would flag women with two or
      more visits for any of the symptoms in the previous 2-month period was examined.
      RESULTS: Of the 223,903 insured women, 161 had incident cases of ovarian cancer.
      Both early and late-stage patients had a higher prevalence of abdominal/pelvic
      pain and bloating than the comparison groups, primarily in the 3 months before
      diagnosis. The passive screener had a sensitivity of 0.31 and specificity of 0.83
      and usually identified women right before diagnosis. Assuming an average cost of
      $500 per false positive, the screener would be considered cost-effective if the
      true positives had an average increase of 8.5 years of life expectancy.
      CONCLUSIONS: These results support previous findings that ovarian cancer symptoms
      were reported in health insurance claims and were more prevalent before
      diagnosis, but the symptoms may occur too close to the diagnosis date to provide
      useful diagnostic information. The passive screening approach should be
      reevaluated in the future using electronic medical records; if found to be
      effective, the method may be potentially useful for other incident diseases.

PMID- 20156132
TI  - Recent patents on plant transgenic technology.
AB  - Plant transformation technology plays an ever-increasing role in improving crop
      plant traits and addressing research questions. In recent years, a number of
      important patents on plant transgenic technologies have been published.These
      patents represent significant new progresses, many representing novel approaches
      in the field of plant transgenic technology. This review highlights selected as
      well as the most significant advancements made mostly within the past 2 years in
      plant transgenic research. These advancements include the improvements of plant
      transformation systems, development of new plant selectable markers, engineering
      for plant stress tolerance, production of vaccines in transgenic plants, etc. Of
      these, the engineering for plant stress tolerance accounts for a high percentage
      of the transgenic field of inventions. Some results are drastic and unexpected,
      having a great potential in their applications towards a wider range of plant
      species. This review also tries to avoid terms and languages pertaining to the
      patent and legal documents to ease readings.

PMID- 20156133
TI  - Genus vaccinium: medicine, cosmetics, and coatings.
AB  - Vaccinium is a genus of shrubs several of which, including cranberry,
      lingonberry, and blueberry, produce edible fruit. Consumption of the fruit of
      these plants and juices pressed from it has long been known to have healthful
      effects. A number of functional compounds have been extracted from the fruits and
      seeds of these plants. Anthocyanidins and related compounds have been reported to
      possess antimicrobial, antioxidant, and anti-inflammatory properties. Extracts of
      the fruits have been applied to the inhibition of non-enzymatic glycosylation in
      anti-aging preparations. The oil of the cranberry seed is high in antioxidants
      and is a source of omega-3, -6, and -9 fatty acids making it an attractive
      cosmetics component. The inhibition of tumor growth, angiogenesis, and metastasis
      by extracts of these fruits has been described. Extracts of the plants have also
      been applied to the development of antimicrobial paints and coatings. Here, we
      provide an overview of the wide range of applications described for various
      compounds from and preparations of these plants and survey the recent patents
      related to those applications.

PMID- 20156134
TI  - A method for the isolation of protoplasts from grape berry mesocarp tissue.
AB  - As single cell systems, protoplasts have been used in physiological, biochemical
      and molecular studies aiming towards the investigation, improvement or
      modification of plants. In grapevine, protoplasts have been isolated from several
      source tissues but not from grape berry, a major challenge given the uniqueness
      of grape fruit for human diet and wine production. Also, as the ripe grape berry
      has long been considered a 'small bag of sugary water' without cell
      compartmentation and/or membrane integrity, the isolation of intact cells from
      the mesocarp is of special scientific significance. Protoplasting from grape
      berry mesocarp cells was achieved with cellulase and pectolyase digestion,
      followed by differential and gradient centrifugations; however, given the special
      characteristics of berry tissue, cell wall digestion and protoplast purification
      were performed in a special environment to maintain their integrity and
      viability. Light and epifluorescence microscopy revealed the spatial organization
      of the cytoplasm, where an intricate acidic vacuolar apparatus predominates
      supporting the idea that berry softening during ripening is not strictly
      associated with loss in compartmentation and/or membrane integrity. Following the
      worldwide economical and social importance of wine in modern days, grape berry
      protoplasts are a major advance for both basic research of fruit ripening and
      biotechnological applications.

PMID- 20156135
TI  - Recent patents on imaging nanoprobes for brain tumor diagnosis and therapy.
AB  - Multifunctional nanoprobes, such as nanocrystals, nanoshells, and luminescent
      nanomaterials, have been developed for imaging biological processes; such as cell
      signaling, neuroimaging, protein conformation probing, DNA conformation probing,
      gene transcription, virus infection and replication in cells, protein dynamics,
      tumor diagnosis, and therapy evaluation. With the application of nanotechnology
      for CNS-active agents' delivery, nanostructured materials are emerging as a
      powerful means for diagnosis of CNS disorders, including brain tumors, because of
      their unique optical size, and surface properties. This review summarizes the
      recent patents on imaging nanoprobes for brain tumor diagnosis and therapy. The
      future development in this active cross-disciplinary field will be discussed as
      well.

PMID- 20156136
TI  - Transporter-mediated multidrug resistance and its modulation by Chinese medicines
      and other herbal products.
AB  - The main cause of failure in cancer drug therapy is the emergence of cellular
      resistance to drugs. Cancer cells, after exposure to one drug, can become
      simultaneously insensitive to mechanistically and chemically unrelated drugs, a
      phenotype known as multidrug resistance (MDR). Although a number of mechanisms
      have been proposed to mediate MDR, the classical cellular mechanism involves the
      overexpression of several members of the ATP-binding cassette (ABC) superfamily
      of transporters, leading to increased efflux and decreased intracellular drug
      accumulation. Among these, P-glycoprotein (P-gp, ABCB1), MRP1 (ABCC1) and BCRP
      (ABCG2) are the main transporters conferring MDR. These transporters are
      frequently detected in recurrent cancer cells or cancer stem cells. To overcome
      MDR, various studies have been conducted to investigate potential to discover
      effective MDR modulators from Chinese medicines (CMs) and other herbal products
      because many of these have been used for centuries without harmful side effects.
      This review summarizes: i) The contribution of P-gp, MRP1 and BCRP in cancer drug
      resistance; ii) known mechanisms of action for MDR modulators; iii) commonly used
      methods for identification and evaluation of novel modulators of transporter
      mediated MDR; and iv) the modulating effects of CMs and other natural products on
      ABC transporters and MDR. The CM and their active components with potent
      modulating effects on MDR can be considered as promising lead agents for the
      design of more effective and less toxic drugs to overcome MDR.

PMID- 20156137
TI  - Chemoinformatics approaches for traditional Chinese medicine research and case
      application in anticancer drug discovery.
AB  - Traditional Chinese Medicine (TCM), which has been used for thousands of years to
      treat diseases, provides unique theoretical and practical methodologies for
      disease control. With the increasing accumulation of TCM data, it is imperative
      to study and analyze these resources with modern technologies and to elucidate
      the molecular mechanisms of TCM therapy. However, the philosophy, framework and
      technique of TCM are quite different from those of Western medicine, which causes
      complications when attempting to design modern drug treatments based on TCM. To
      meet this challenge, some basic chemoinformatics techniques, including molecular
      similarity searching, virtual screening and inverse docking, have been utilized
      in an attempt to gain a deeper understanding of TCM and to accelerate the TCM
      based drug discovery. Recent progress on the use of chemoinformatics in TCM
      research will be discussed and an example of the preliminary application of
      chemoinformatics methods in anticancer drug design will be provided.

PMID- 20156138
TI  - Longevity depends on a balance between proinflammatory and anti-inflammatory
      factors: use of TCMS and natural products.
AB  - During the course of our investigation of longevity promoting natural products
      and Chinese herbs in the last 15 years, we come to the conclusion that in order
      to have healthy, productive and graceful maturing, it is necessary to maintain a
      dynamic balance between proinflammatory and anti-inflammatory loads. This may
      also help to prevent cancer as well as premature degeneration of various organ
      systems. Modern life style and food intake tend to overload proinflammatory
      factors. To overcome this it is desirable to regularly consume fresh fruits,
      vegetables and multiple grains, various beans including soybeans and/or minimally
      processed, unbleached products. When this is not sufficient or possible, taking
      proper dietary supplements under the guidance of knowledgeable health
      professional can be helpful.

PMID- 20156139
TI  - Merging traditional Chinese medicine with modern drug discovery technologies to
      find novel drugs and functional foods.
AB  - Traditional Chinese Medicines (TCM) are rapidly gaining attention in the West as
      sources of new drugs, dietary supplements and functional foods. However, lack of
      consistent manufacturing practices and quality standards, fear of adulteration,
      and perceived deficiencies in scientific validation of efficacy and safety impede
      worldwide acceptance of TCM. In addition, Western pharmaceutical industries and
      regulatory agencies are partial toward single ingredient drugs based on synthetic
      molecules, and skeptical of natural product mixtures. This review concentrates on
      three examples of TCM-derived pharmaceuticals and functional foods that have,
      despite these usual obstacles, risen to wide acceptance in the West based on
      their remarkable performance in recent scientific investigations. They are: Sweet
      wormwood (Artemisia annua), the source of artemisinin, which is the currently
      preferred single compound anti-malarial drug widely used in combination therapies
      and recently approved by US FDA; Thunder god vine (Tripterygium wilfordii) which
      is being developed as a botanical drug for rheumatoid arthritis; and green tea
      (Camellia sinensis) which is used as a functional beverage and a component of
      dietary supplements.

PMID- 20156141
TI  - Use of compound Chinese medicine in the treatment of lung cancer.
AB  - Traditional Chinese/herbal medicine (TCM) is now commonly used by cancer patients
      of Asian ethnicity to supplement or replace prescribed treatments. The overall
      survival rate for lung cancer has not improved significantly in the past several
      decades; it remains the leading cause of cancer death. Much more attention has
      been paid by clinicians and researchers to the possible use of compound Chinese
      medicine (CCM) as effective anti-lung cancer medicines. In this review, we
      briefly summarize the clinical and experimental status of numerous CCMs recently
      developed primarily in China for the treatment of lung cancer, including
      formulations, treatment effectiveness, and molecular mechanisms. By presenting
      this information, our goal is to possibly open up new future avenues for the
      practice of lung cancer treatment.

PMID- 20156140
TI  - Targeting tumor proteasome with traditional Chinese medicine.
AB  - The proteasome is a multicatalytic protease complex whose activity is required
      for the growth of normal or tumor cells. It has been shown that human cancer
      cells are more sensitive to proteasome inhibition than normal cells, indicating
      that the proteasome could be a target of chemotherapy. Studies suggest that
      traditional Chinese medicine (TCM) is an effective approach for cancer treatment.
      Here we reviewed several TCMs for their potential in treatment of cancer. This
      short review focuses mainly on the TCMs that potentially target the tumor
      cellular proteasome and NF-kappaB pathway whose activation is dependent on the
      proteasome activity.

PMID- 20156142
TI  - Traditional Chinese medicines (TCMs) for molecular targeted therapies of tumours.
AB  - Scientific progress in genetics, cell and molecular biology has greatly
      ameliorated our comprehensive understanding of the molecular mechanisms of
      neoplastic transformation and progression. The rapidly advancing identification
      of molecular targets in human cancers during the last decade has provided an
      excellent starting point for the development of novel therapeutics. A huge
      variety of potential molecular targets have been identified, many of which are
      already in the market for therapeutic purposes. It is now becoming possible to
      target pathways and/or molecules that are crucial in maintaining the malignant
      phenotype. Traditional Chinese medicine (TCM) is often considered as alternative
      or complementary medicine. TCM represents a holistic approach and lacks high
      quality scientific evidence on its effectiveness. Therefore, it is frequently
      regarded with some scepticism by western academic medicine. In this review, we
      report that application of modern technologies allowed identification of novel
      molecular targets modulating the anti-tumour activity of natural products derived
      from TCM. Moreover, we tried to cross the bridge between TCM and Western modern
      medicine to be able to implement them for the sake of cancer patients.

PMID- 20156143
TI  - Application of chemistry-based functional proteomics to screening for novel drug
      targets.
AB  - Pharmaceutical companies are being forced by market competition to find new ways
      of novel drug target screening instead of traditional methods. The completion of
      human genome sequencing has provided a flood of new information that might help
      identify potential drug targets. Finding promising novel drug targets from this
      flood of information remains challenging. For de novo target screening, the
      interactions between a drug and cellular components must be comprehensively
      characterized for better understanding of the pharmacological activities of the
      drug. The multidisciplinary chemistry-based functional proteomics can be used to
      elucidate the interactions, because it provides a method to focus initial new
      drug target identification towards proteins that are more easily validated and
      most likely to be effective, thereby creating a higher potential for success.
      This review covers major chemistry-based functional proteomic approaches and
      highlights their recent advances in applications for novel drug target screening.

PMID- 20156144
TI  - An instrument-based screening assay for DNA-targeted anticancer drugs using
      resonance light scattering.
AB  - DNA is a valid drug target for development of target-based therapeutics against
      cancer. Screening DNA-targeted anticancer drugs is a key process for the research
      and development of new anticancer drugs. The traditional anticancer drug
      screening methods, including animal experiments and cell-based screening assays,
      have unavoidable drawbacks. In this contribution, the new instrument-based
      screening assay for DNA-targeted anticancer drugs in vitro using resonance light
      scattering (RLS) technique was proposed. The experiments suggested that the
      increment of RLS intensity was directly proportional to the antitumor effect of
      anticancer drugs. Therefore, it was intuitive to obtain the sequence of the
      antitumor activity of four anticancer drugs without data processing as follows:
      mitoxantrone (MIT) > pirarubicin (PIR) > daunorubicin (DAU) > doxorubicin (DOX)
      by RLS screening spectra. Moreover, the apparent equilibrium constant (K) was
      1.23 x 10(4), 2.22 x 10(4), 4.66 x 10(4) L/mol for DOX, DAU, and PIR,
      respectively. The inhibitory concentration 50 (IC50) was 0.148, 0.102, 0.025,
      0.013 micromol/L for DOX, DAU, PIR, MIT, respectively. Therefore, the antitumor
      effect of four drugs was as follows: MIT > PIR > DAU > DOX, which was in good
      agreement with the result obtained from RLS screening assays. The mechanism
      between DNA and anthracycline drugs was investigated using UV-vis spectroscopy,
      fluorescence spectroscopy, and electrophoresis experiments. The proposed assay is
      a rapid, intuitive, and easy-to-conduct bioassay with good accuracy and
      reproducibility.

PMID- 20156145
TI  - High throughput bioassays using nanoparticles.
AB  - An overview of the usefulness of different nanoparticles to improve the features
      of high throughput separation and individual and multiplexed detection bioassays
      is presented. Although the development of microarray and microfluidic systems has
      expanded the capabilities of these high throughput assays, the combined use of
      NPs and these devices has provided them with new applications in drug discovery,
      proteomic and genomic studies, and clinical diagnosis. This article reviews the
      wide application field of magnetic, gold, silver, semiconductor and other
      nanoparticles in high throughput bioassays. Also, the versatility of the
      detection systems described shows that NPs are useful alternatives to fluorescent
      dyes, which are often used in these assays.

PMID- 20156146
TI  - High throughput screening and evolution of a library of ligands in asymmetric H
      transfer reduction of acetophenone.
AB  - A library of 117 ligands was combined with three transition metals Ru, Rh and Ir
      and screened with three different operating conditions for the asymmetric H
      transfer reduction of acetophenone into phenylethanol. The combinatorial approach
      was based on evolution of a first library containing 60 ligands. For the
      evolution, operators such as replication, regression, cross-over and mutation
      were used. The study was performed with a XYZ robot and fast chiral GC analysis.
      Over only 4 generations, the average targeted criterion, enantioselectivity, was
      increased from 20% to ca. 80% for the 4th generation. The best results provided
      enantiomeric excess up to 93%.

PMID- 20156147
TI  - Coupling the inhibition of viral transduction with a positive fluorescence
      signal.
AB  - Cell-based assays for the inhibition of viral infections most commonly couple a
      positive signal (e.g., an increase in fluorescence) to the infection itself and
      not to its inhibition. When performing drug screens, compounds decreasing the
      signal are therefore considered as putative inhibitors. However, this approach
      can cause the selection of many false positives, since, for example, both killing
      of the host cell and inhibiting viral cell-entry results in the same signal.
      Using a model system based on murine leukemia virus (MLV) particles pseudotyped
      with the G-protein of vesicular stomatitis virus (VSV-G), we have developed
      generic assays coupling a positive readout to the inhibition of viral
      transduction. Consequently, the system favors drug candidates (and concentrations
      thereof) that do not harm human cells and significantly decreases the probability
      for selecting false positives. The assay allows Z-factors of approximately 0.9,
      takes cytotoxic side effects into account and could in theory be adapted for high
      throughput screening of inhibitors against further viral species.

PMID- 20156148
TI  - Directed evolution toward improved production of L-ribose from ribitol.
AB  - Improvement of the one-step production of L-ribose from ribitol using a
      recombinant Escherichia coli is described. The gene encoding the enzyme mannitol
      1-dehydrogenase (MDH) from Apium graveolens has previously been codon-optimized,
      cloned into the constitutive pZuc10 vector, and expressed in E. coli. This MDH
      catalyzes the NAD-dependent conversion of mannitol to D-mannose and has the
      ability to convert several polyols to their L-sugar counterparts, including
      ribitol to L-ribose. Here, three rounds of directed evolution using libraries
      generated through error-prone PCR and screened using a dinitrosalicylate reagent
      were prepared. Mutants were selected for improved conversion of L-ribose, and the
      best mutant was isolated by combining two round 2 mutations. Libraries were also
      selected for thermal stability and screened at increasingly higher temperatures
      with each round of mutagenesis. An overall 19.2-fold improvement was observed
      with a final conversion of 46.6 +/- 1.7% and a productivity of 3.88 +/- 0.14 gL(
      1)d(-1) in 50 mL shaken flasks at 34 degrees C. Further characterization of the
      mutants suggests that increased enzyme thermal stability and expression are
      responsible for the increase in L-ribose production. The mutant E. coli
      production strain isolated represents an improved system for large-scale
      production of L-ribose.

PMID- 20156149
TI  - High throughput discovery of families of high activity WGS catalysts: part I-
      history and methodology.
AB  - State-of-art water gas shift catalysts (FeCr for high temperature shift and CuZn
      for low temperature shift) are not active enough to be used in fuel processors
      for the production of hydrogen from hydrocarbon fuels for fuel cells. The need
      for drastically lower catalyst volumes has triggered a search for novel WGS
      catalysts that are an order of magnitude more active than current systems. Novel
      catalytic materials for the high, medium and low temperature water gas shift
      reactions have been discovered by application of combinatorial methodologies.
      Catalyst libraries were synthesized on 4 inch wafers in 16 x 16 arrays and
      screened in a high throughput scanning mass spectrometer in the temperature range
      200 degrees C to 400 degrees C. More than 200 wafers were screened under various
      conditions and more than 250,000 experiments were conducted to comprehensively
      examine catalyst performance for various binary, ternary and higher-order
      compositions.

PMID- 20156150
TI  - A review of clinical pharmacokinetics and pharmacodynamics of galantamine, a
      reversible acetylcholinesterase inhibitor for the treatment of Alzheimer's
      disease, in healthy subjects and patients.
AB  - Galantamine is a reversible acetylcholinesterase inhibitor for the treatment of
      Alzheimer's disease. Following oral administration, galantamine is rapidly
      absorbed and reaches C(max) in approximately one hour for immediate release (IR)
      tablets and four hours for extended-release (ER) capsules. Food has no clinically
      important effects on the absorption of galantamine. Galantamine displays dose
      proportional pharmacokinetics over a dose range of 8-32 mg and 8-24 mg for IR and
      ER formulations, respectively. The elimination half-life of galantamine is about
      7-8 hours. Galantamine has low protein binding (28.3-33.8%) and has an apparent
      steady-state volume of distribution (V(ss)) of 193 L. Approximately 20-25% of the
      galantamine dose administered is excreted unchanged in urine. No clinically
      significant effects of age, gender, and race have been observed on galantamine
      pharmacokinetics. The exposures to galantamine in patients with moderate and
      severe renal impairment are 37% and 67% higher, respectively than in healthy
      subjects, whereas the exposure to galantamine is approximately 30% higher in
      patients with moderate hepatic impairment. Co-administration of galantamine with
      ketoconazole (CYP 3A4 strong inhibitor) or paroxetine (CYP 2D6 strong inhibitor)
      leads to a 30% and 40% increase, respectively, in galantamine exposure compared
      to galantamine given alone.

PMID- 20156151
TI  - Intraperitoneal drug therapy: an advantage.
AB  - The peritoneum is a cavity which has been successfully utilized by nephrologists
      to perform peritoneal dialysis (PD) in patients with renal failure. The
      physiologic characteristic of the peritoneal cavity not only helps remove toxic
      metabolites from the body, but also provides a useful portal of entry in the body
      for several pharmacological agents. Several medications such as antibiotics are
      given via the intraperitoneal (IP) route in PD patients to treat episodes of
      peritonitis. More recently the IP route has been used for chemotherapy in
      patients with intra-abdominal malignancies, i.e. gynecological and
      gastrointestinal cancers and has shown very promising results. In patients with
      peritoneal surface malignancies, perioperative IP chemotherapy has been used with
      good results. The rate and amount of drug transfer in the peritoneum are
      dependent on several factors. Factors such as peritoneal inflammation, surface
      area, peritoneal blood flow, time of contact, etc, influence the drug transfer.
      This review discusses the usefulness of IP drug therapy and the factors
      influencing it, as well as strategies to increase the efficacy, and conclude that
      IP route is an alternate route to the more conventional drug delivery routes, and
      can be successfully used when the target is within the peritoneal cavity or
      adjacent tissue.

PMID- 20156152
TI  - Pharmacotherapy of mixed dyslipidemia in the metabolic syndrome.
AB  - People with metabolic syndrome (MetS) are at increased risk of type 2 diabetes
      and cardiovascular diseases, and often have increased triglyceride, reduced high
      density lipoprotein cholesterol (HDL-C) and sometimes moderately increased low
      density lipoprotein cholesterol (LDL-C) levels. Lifestyle intervention is
      critical for treating MetS, while pharmacotherapy of dyslipidemia in MetS remains
      controversial. Considering the specific lipid profile in MetS, fibrates are
      typically used as first-line treatment. Nevertheless, first-line therapy should
      be directed towards LDL-C, even in people with MetS, because of the evidence that
      lowering LDL-C has cardioprotective effects. Non-HDL-C is considered to be an
      alternative treatment target for people with moderately or severely elevated
      triglyceride (> or =200mg/dl). Statins improve lipid profiles principally by
      lowering LDL-C and may exert anti-inflammatory and anti-atherothrombogenic
      effects, which ameliorate the fundamental pathophysiology of MetS. Fibrates also
      have pleiotropic effects that improve cardiometabolic risk factors, including
      insulin resistance, although they do not have clear cardioprotective effects.
      Omega-3 fatty acids, niacin, pioglitazone and anti-obesity drugs are also
      candidates for the treatment of dyslipidemia and other complications in MetS.
      Another question is whether statins in combination with fibrates or other lipid
      lowering drugs has greater cardioprotective properties than monotherapy. In this
      article, we discuss several issues in the pharmacotherapy of MetS.

PMID- 20156153
TI  - Pretreatment by hyperoxia--a tool to reduce ischaemia-reperfusion injury in the
      myocardium.
AB  - Atherosclerosis leads to narrowing and occlusion of coronary arteries, resulting
      in inadequate oxygen supply for maintenance of normal oxidative metabolism. To
      avoid profound ischaemia and subsequent necrosis of cardiomyocytes, blood flow
      has to be restored by means of thrombolysis, percutaneous coronary intervention,
      or surgical revascularisation. Besides restoring oxygen supply to the cells,
      introduction of molecular oxygen to the ischaemic tissue results in a spectrum of
      unfavourable events, termed altogether as reperfusion injury. Exposure to
      hyperoxia for a limited time before ischaemia induces a low-grade oxidative
      stress and evokes an (ischaemic) preconditioning-like effect in the myocardium,
      which protects the heart from subsequent injury. This review addresses the
      effects of pretreatment by hyperoxia both in experimental and clinical setting.

PMID- 20156154
TI  - The treatment of cardiovascular disease continuum: focus on prevention and RAS
      blockade.
AB  - The cardiovascular disease continuum is a sequence of events, which begins with a
      host of risk factors consisting of diabetes mellitus, dyslipidemia, hypertension,
      smoking and visceral obesity. If left untreated, it will inexorably progress to
      atherosclerosis, CAD, myocardial infarction, left ventricular remodeling, LVH,
      left ventricular enlargement, and eventually end-stage heart failure and death.
      Treatment intervention at any stage of its course will prevent or delay its
      further progression. However, the best results are expected to be achieved when
      treatment is initiated at the beginning, or at an early stage of its course. A
      Pub-Med/MEDLINE search was conducted for relevant English language, randomized
      clinical trials and epidemiologic studies for the years 1995-2009 using the
      terms, cardiovascular continuum, obesity, hyperlipidemia, diabetes mellitus,
      hypertension, metabolic syndrome, renal disease, stroke, and blockers of the
      renin angiotensin system (RAS). A total of 34 pertinent studies were selected for
      review. This concise review will focus on prevention and the aggressive treatment
      of the existing cardiovascular risk factors with emphasis on the blockers of RAS,
      and demonstrate that RAS blockers are the best drugs for its treatment.

PMID- 20156155
TI  - Hepatitis C virus infection and antiviral treatment in marginal zone lymphomas.
AB  - The association between hepatitis C virus (HCV) infection and B-cell non
      Hodgkin's lymphomas has been demonstrated in epidemiological studies, in
      particular in highly endemic geographical areas such as Italy, Japan and southern
      parts of United States. Marginal zone lymphomas are the histotypes that are most
      frequently associated with HCV infection. The WHO classification comprises
      extranodal marginal zone B-cell lymphoma of MALT type, splenic marginal zone B
      cell lymphoma and nodal marginal zone B-cell lymphoma. Recently, antiviral
      treatment has been proved to be effective in the treatment of HCV-positive
      patients with indolent lymphoma, prevalently of marginal zone origin. This is the
      strongest evidence of a causative link between HCV and lymphomas. Aim of this
      review is to illustrate the relationship between HCV infection and marginal zone
      lymphomas and to systematically summarize the data from the therapeutic studies
      where antiviral treatment with alpha-interferon with or without ribavirin was
      employed in patients with marginal zone lymphomas.

PMID- 20156156
TI  - Clinical pharmacology and lesion penetrating properties of second- and third-line
      antituberculous agents used in the management of multidrug-resistant (MDR) and
      extensively-drug resistant (XDR) tuberculosis.
AB  - Failure of first-line chemotherapy to cure tuberculosis (TB) patients occurs, in
      part, because of the development of resistance to isoniazid (INH) and rifampicin
      (RIF) the two most sterilizing agents in the four-drug regimen used to treat
      primary infections. Strains resistant to both INH and RIF are termed multidrug
      resistant (MDR). Treatment options for MDR patients involve a complex array of
      twenty different drugs only two classes of which are considered to be highly
      effective (fluoroquinolones and aminoglycosides). Resistance to these two classes
      results in strains known as extensively drug-resistant (XDR) and these types of
      infections are becoming increasingly common. Many of the remaining agents have
      poorly defined pharmacology but nonetheless are widely used in the treatment of
      this disease. Several of these agents are known to have highly variable exposures
      in healthy volunteers and little is known in the patients in which they must be
      used. Therapeutic drug monitoring (TDM) is infrequently used in the management of
      MDR or XDR disease yet the clinical pharmacokinetic studies that have been done
      suggest this might have a large impact on disease outcome. We review what is
      known about the pharmacologic properties of each of the major classes of second-
      and third-line antituberculosis agents and suggest where judicious use of TDM
      would have the maximum possible impact. We summarize the state of knowledge of
      drug-drug interactions (DDI) in these classes of agents and those that are
      currently in clinical trials. Finally we consider what little is known about the
      ability of TB drugs to reach their ultimate site of action--the interior of a
      granuloma by penetrating the diseased lung area. Careful consideration of the
      pharmacology of these agents is essential if we are to avoid further fueling the
      growing epidemic of highly drug-resistant TB and critical in the development of
      new antituberculosis drugs.

PMID- 20156157
TI  - Click-chemistry reactions in radiopharmaceutical chemistry: fast & easy
      introduction of radiolabels into biomolecules for in vivo imaging.
AB  - Today the term "click chemistry" is often used equivalent with the copper
      catalyzed 1,3-dipolar Huisgen cycloaddition. Originally, the concept was
      introduced in 2001 to describe reactions fulfilling a set of criteria that are
      most useful for chemical syntheses in drug research. In radiopharmaceutical
      chemistry where short lived radioisotopes are introduced into various different
      substance classes for in vivo imaging of biochemical processes, the expanding
      field of radioactive bioconjugation has become predominant. Labeled biomolecules
      such as peptides, proteins and oligonucleotides generated via bioconjugation of
      chelators for radiometal introduction as well as novel valuable secondary
      precursors for (18)F labeling have enriched the growing field of molecular
      imaging substantially. When introducing radioactive nuclides with a very short
      half-life into biomolecules, some of the typical criteria defined by click
      chemistry are more crucial than others. Time is always the most important issue,
      whereas avoiding the formation of by-products that have to be removed without
      chromatography is of minor importance. The short-lived radionuclide (11)C for
      example has a physical half-life of only 20 min so that the labeling procedure
      cannot exceed 40-60 minutes (2-3 half-lifes). In this contribution, we outline
      reactions and molecules which meet the requirements of click chemistry reactions
      and are suitable for radiosyntheses of short lived SPECT ((99m)Tc: t(1/2) = 6 h,
      (111)In: t(1/2) = 2.81 d) and PET ((11)C: t(1/2) = 20.3 min to (64)Cu: t(1/2) =
      12.7 h) radiotracers for in vivo imaging of biological processes and review the
      contributions in the field of radiochemical "click-reactions" - 1,3-dipolar
      Huisgen cycloadditions and beyond.

PMID- 20156158
TI  - An overview on different classes of viral entry and respiratory syncitial virus
      (RSV) fusion inhibitors.
AB  - The therapeutic approach to AIDS is based on the combination of different drugs
      in the highly active antiretroviral therapy (HAART) regimen. These drugs have a
      wide variety of side effects, and some strains of HIV can develop resistance: for
      these reasons new anti-HIV drugs are needed. In the wide field of anti-HIV
      medicine this review covers different classes of drugs which inhibit viral entry:
      in particular the classification of main categories, their mode of action and
      some new candidates for AIDS therapy are contemplated. Also covered in this
      review are respiratory syncytial virus (RSV) fusion inhibitors.

PMID- 20156159
TI  - The role of Endothelin-1 in obstructive sleep apnea syndrome and pulmonary
      arterial hypertension: pathogenesis and Endothelin-1 antagonists.
AB  - Obstructive Sleep Apnea Syndrome (OSAS) is a recognized risk factor for
      cardiovascular disorders and in some cases is complicated with Pulmonary Arterial
      Hypertension (PAH), as the endothelium is affected. Recent studies provide strong
      evidence for endothelial dysfunction in obstructive sleep apnea. The resultant
      vasoconstriction, abnormal cell proliferation and hyper-coagulability may lead to
      the initiation or progression of atherosclerotic cardiovascular and
      cerebrovascular disorders, which are frequently encountered in OSA patients.
      While the currently available therapies for OSAS, such as Continuous Positive
      Airway Pressure therapy (CPAP therapy), improve endothelial dysfunction, they are
      not well-tolerated by patients. CPAP therapy can reduce nocturnal hypoxemias and
      decrease noradrenaline circulating levels, but does not affect ET-1 plasma
      levels. Potent and selective Endothelin-1 receptor antagonists have been
      developed and have shown promising results in the treatment of cardiovascular
      diseases such as pulmonary arterial hypertension, acute and chronic heart
      failure, hypertension, renal failure, and atherosclerosis. However, results are
      often contrasting and complicated because of the tissue-specific vasoconstrictor
      actions of Endothelin-B receptors and the fact that endothelin is an autocrine
      and paracrine factor whose activity is difficult to measure in vivo.

PMID- 20156160
TI  - The role of oligodendrocytes in the molecular pathobiology and potential
      molecular treatment of cervical spondylotic myelopathy.
AB  - Cervical spondylotic myelopathy (CSM) is a very common and debilitating disease;
      however, its underlying pathocellular process remains uncertain. Attempts have
      been made to reproduce CSM in experimental animal models in order to deepen the
      knowledge on the molecular pathobiology of this disease. The up-to-date
      observations have established the apoptosis of oligodendrocytes (OLGs) as the
      principal pathocellular process of CSM. Since favorable neurological recovery
      cannot be obtained in afflicted patients, even after the decompression surgery,
      elucidation of the apoptotic cascade in OLGs may unveil possible molecular
      treatments which could inhibit demyelination and ameliorate the neurological
      deficits. Moreover, additional therapeutic benefits may include improvement of
      myelin self-repair capability by stimulating OLG progenitor cells to become
      mature and finally, myelinating OLGs. This review focuses on the factors and
      mechanisms of crucial importance for developing antiapoptotic treatments.
      Critical evaluations of the role of OLGs in molecular pathobiology of CSM as well
      as strategies for potential remyelination of CSM are also provided. The analyses
      and evaluations of the experimental findings can possibly lead to treatment of
      CSM as well as to development of novel biopharmacenticals.

PMID- 20156161
TI  - Dehydroepiandrosterone (DHEA): a steroid with multiple effects. Is there any
      possible option in the treatment of critical illness?
AB  - DHEA is the major circulating steroid in human blood and it is a central
      intermediate in the metabolic pathway of sex steroid hormone formation. Although
      the specific effect of DHEA is still unclear it was demonstrated that DHEA
      modulates several physiologic processes including metabolism and cardiovascular
      function. Furthermore, a profound immunomodulatory effect of DHEA was reported.
      Several data demonstrate the beneficial effect of DHEA in situations of critical
      illness including trauma hemorrhage and sepsis. Accordingly DHEA improved the
      survival rate and clinical situation in several animal models of trauma
      hemorrhage and systemic inflammation. This effect was paralleled by profound
      changes of immunologic parameters, organ function, and heat shock protein
      production. Therefore, it was claimed that DHEA may be a new alternative/additive
      in the treatment of trauma and sepsis. In line, DHEA is a frequently used drug in
      the field of anti-aging medicine, it is an over-the-counter drug in several
      countries, and it was reported that DHEA medication is free of major side
      effects. Therefore, DHEA could easily be used in a clinical trial investigating
      its effects in critical ill patients. This article reviews the reported effects
      of DHEA on the base of the literature with the specific focus on trauma and
      sepsis/critical illness including its clinical perspectives.

PMID- 20156162
TI  - The emerging role of histology in the choice of first-line treatment of advanced
      non-small cell lung cancer: implication in the clinical decision-making.
AB  - Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell
      lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes
      squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The
      majority of patients have advanced disease at diagnosis, and medical treatment is
      the cornerstone of management. Several randomized trials comparing third
      generation platinum-based doublets concluded that all such combinations are
      comparable in their clinical efficacy, failing to document a difference based on
      histology. However, recent evidences, arising from the availability of
      pemetrexed, have shown that histology represents an important variable in the
      decision making. The major progresses in the understanding cancer biology and
      mechanism of oncogenesis have allowed the development of several potential
      molecular targets for cancer treatment such as vascular growth factor and its
      receptors and epidermal growth factor receptor. Targeted drugs seem to be safer
      or more effective in a specific histology subtype. All of these data have led to
      choose the optimal first-line treatment of advanced NSCLC based on histologic
      diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis
      of NSCLC histologic subtype is mandatory. This review will discuss these new
      evidences in the first-line treatment of advanced NSCLC and their implication in
      the current clinical decision-making.

PMID- 20156163
TI  - Pyrimidine nucleosides in molecular PET imaging of tumor proliferation.
AB  - Human thymidine kinase (TK1) is a key enzyme that is up-regulated in cancer cells
      and phosphorylates thymidine and some of its analogs to their monophosphates. The
      monophosphates are converted to their di- and triphosphates by the nucleoside
      kinases, and some of these nucleoside triphosphates are incorporated into DNA by
      DNA polymerase. The nucleoside analogs are transported into cells by
      concentrative nucleoside transporter or equilibrative nucleoside transporter.
      Given the unique property of TK1 and the nucleoside transporter systems,
      thymidine and its analogs have been radiolabeled for positron emission tomography
      (PET) imaging of tumor proliferation and DNA synthesis. Because thymidine is
      catabolized in vivo by thymidine phosphorylase, radiolabeled thymidine has not
      been successful in PET imaging of tumor proliferation. However, some of its
      analogs have been radiolabeled and successfully used in PET imaging of cell
      proliferation as well as DNA synthesis. Much work has been done in synthesis,
      radiosynthesis, and biological evaluation of these analogs for PET imaging of
      tumor proliferation. We review the chemistry, radiochemistry, and biological
      studies published to date, including structure activity relationship and PET
      imaging of the radiolabeled thymidine analogs. Information on radiolabeling and
      PET imaging with various nucleoside analogs is presented.

PMID- 20156164
TI  - New insights into biological markers of frontotemporal lobar degeneration
      spectrum.
AB  - In the last decade, there has been enormous progress in our understanding of
      Frontotemporal Lobar Degeneration (FTLD). Published clinicopathological series
      have clearly demonstrated an overlap between the clinical syndromes subsumed
      under the term frontotemporal dementia and the Progressive Supranuclear Palsy
      (PSP), and the Corticobasal Degeneration (CBD) syndrome. From a neuropathological
      point of view, two broad pathological subdivisions of FTLD are currently
      recognized: a) tau-positive pathology due to the accumulation of various forms of
      the microtubule-associated protein tau, that encompasses FTLD with Pick bodies,
      PSP and CBD, and b) tau-negative pathology, mainly characterized by ubiquitin/TDP
      43-immunoreactive inclusions and in some cases due to Progranulin mutations.
      Several biological markers in cerebrospinal fluid and in blood have been
      evaluated to identify monogenic forms of FTLD and to differentiate either FTLD
      spectrum disorders or FTLD from other neurodegenerative disorders. The proposed
      biomarkers are primarily related to the mechanisms underlying the accumulation of
      the abnormal proteins in FTLD such as Tau, TDP-43 and Progranulin. These
      biomarkers may support the accurate diagnosis of the specific diseases causing
      FTLD, can be useful in assessing efficacy during pharmacological trials, and may
      help in identifying new molecular targets for treatment approaches. In this
      review, we summarise the most recent findings on biological markers and their
      usefulness in clinical practice for the diagnosis and management of FTLD.

PMID- 20156165
TI  - Organotypic cultures as tool to test long-term effects of chemicals on the
      nervous system.
AB  - The study of neuroscience has vastly benefited from the use of brain slices. This
      preparation has been fundamental for the understanding of the cellular basis of
      nervous system function as well as for the study of the mechanisms involved in
      neuronal network dysfunction. This experimental model provides flexible access,
      and control of, specific neural circuits and maintains their basic properties,
      allowing them to reproduce most of their natural network activities. Brain slices
      permit the combination of sophisticated techniques such as electrophysiology,
      fluorescence imaging, pharmacology, molecular biology, etc. More recently, the
      development of organotypic brain slice cultures has expanded the use of modern
      technical approaches to the study neuronal networks, while increasing their
      possibilities of evaluating long-term effects of acute experimental conditions,
      as well as the effects of chronic treatments on neuronal network function in
      vitro. Here, I will provide an overview of the use of organotypic cultures to
      understand neuronal network function and dysfunction, as well as the
      pharmacological approaches used for these studies. As a final example, I will
      review the studies performed in organotypic cultures regarding the deleterious
      effects of long-term amyloid beta application on neuronal networks in vitro, as
      well as the use of drugs that may prevent or revert their deleterious effects on
      nervous system function. Overall, this review will provide elements to support
      the use of organotypic cultures as a very reliable model to explore long-term
      neuropharmacological studies in vitro.

PMID- 20156166
TI  - Tyrphostins as potential therapeutic agents for acute kidney injury.
AB  - Acute kidney injury (AKI) is a syndrome characterized by an acute renal cell
      injury that leads to sudden loss of renal function. There are currently no
      clinically validated treatments for AKI besides substituting renal function by
      dialysis. However, new biomarkers will allow an earlier diagnosis, thus providing
      a window of opportunity for therapeutic intervention. Tyrphostins are a family of
      compounds originally designed as protein tyrosine kinase inhibitors. However,
      some molecules of this family have additional actions, such as inhibition of
      guanylate and adenylate cyclases, mitochondrial uncoupling or antioxidant
      effects. We review the potential role of tyrphostins in the prophylaxis and
      treatment of acute kidney injury on the basis of published studies on animals, in
      vitro experiments and piecemeal information from humans. The AG 490 and AG 126
      tyrphostins have recently been shown to protect from AKI in experimental animal
      models of ischemia-reperfusion and sepsis-induced injury. AG 490 protects from
      cyclosporin-induced AKI and AG 1714 protects from cisplatin nephrotoxicity. AG
      490 is nephroprotective by inhibiting oxidative stress-related Janus activated
      kinase-2 (JAK2) activation. Potential applications of AG490 or derivative
      molecules include AKI of nephrotoxic or ischemic nature, or a combination of
      both, as may occur in the immediate postransplant period. The molecular targets
      of AG 126 and AG 1714 are less well characterized. In conclusions, different
      tyrphostins are nephroprotective in animal models of AKI. The characterization of
      the molecular targets involved will allow the design of novel therapies that may
      reach the clinical trial stage.

PMID- 20156167
TI  - The role of heat shock protein (HSP) in atherosclerosis: Pathophysiology and
      clinical opportunities.
AB  - The highly conserved heat-shock proteins (HSPs) from mammals and microbial
      reagents are among the immunogenic proteins. Their expression is induced in
      response to a wide variety of physiological and environmental insults. Their
      functions as molecular chaperones allow cells to adapt to gradual changes in
      their environment and to survive in otherwise lethal conditions. Although the
      role of HSPs in atherosclerosis remains controversial, HSPs were thought to act
      as autoantigens, and trigger both cell- and antibody-mediated immune responses.
      However, HSPs possess immunoregulatory attributes as well and therefore, are
      being exploited for immunomodulation of atherosclerosis either by the adaptive or
      innate immune system. This review will focus on a number of HSPs from different
      families including HSPE, HSPB, DNAJ, HSPD, HSPA, HSPC and HSPH. The role of these
      HSPs, their protective vs. immunogenic properties with special emphasis on their
      potential as targets to develop therapeutic agent against atherosclerosis will be
      discussed.

PMID- 20156168
TI  - Inhibitors of the mitochondrial electron transport chain and de novo pyrimidine
      biosynthesis as antimalarials: The present status.
AB  - Malaria is a major worldwide public health threat with worrying social and
      economic burdens due to the rapid emergence of multidrug-resistant Plasmodium
      falciparum strains. As a result, there is an urgent need to find novel drugs that
      might overcome clinical resistance to marketed antimalarials. In recent years,
      the mitochondrial electron transport chain (mtETC) has been explored for the
      development of new antimalarials. Type II NADH:quinone oxidoreductase (PfNDH2),
      succinate dehydrogenase (SDH) and cytochrome bc1 have become a major focus of
      those efforts, leading to several studies of its biochemistry and the design of
      potent inhibitors. Furthermore, de novo pyrimidine biosynthesis in malaria
      parasites, particularly dihydroorotate dehydrogenase (PfDHODH), is also receiving
      increasing attention. The enzymes involved in the mtETC are valuable targets in
      malaria chemotherapy, not only because they play a critical role in metabolic
      pathways of P. falciparum, but also because they differ significantly from the
      analogous mammalian system. Inhibition of such enzymes results in the shutdown of
      mitochondrial electron flow, leading to the arrest of pyrimidine biosynthesis and
      consequent parasite death. In this review, we aim to outline recent advances in
      the inhibition of mitochondrial metabolic pathways, highlighting the major
      classes of known inhibitors and those that are currently being developed.

PMID- 20156169
TI  - Dihydrobenzo[1,4]oxathiine: A multi-potent pharmacophoric heterocyclic nucleus.
AB  - 2,3-dihydrobenzo[b][1,4]oxathiine represents a valuable pharmacophoric
      heterocyclic nucleus known since very long time. Initially, together with some
      patents reporting the use of these compounds as herbicides or lipogenesis
      inhibitors, several papers reported their ability as melatonin, histamine and
      serotonin receptor ligands, alpha-adrenoreceptor blockers as well as non
      glycoside sweeteners. This wide range of biological activities has been recently
      further improved by studies stating their activity as antimycotics, multi-defense
      antioxidants and estrogen receptor ligands. The last insights regarding the
      preparation, the biological activity and the structure activity relationship
      (SAR) of derivatives containing the dihydrobenzoxathiine skeleton will be
      discussed in this review.

PMID- 20156170
TI  - Fulvestrant - a novel endocrine therapy for breast cancer.
AB  - Fulvestrant is a novel endocrine therapy for breast cancer, with a unique
      structure and mode of action. It binds competitively to the oestrogen receptor
      (ER), with high affinity, and downregulates ER by functional blockade and
      increased turnover. Fulvestrant has reached the clinic via extensive pre-clinical
      and clinical trials, which demonstrated fulvestrant's unique characteristics and
      showed that they translate to equivalent or improved clinical efficacy compared
      to established endocrine agents. Fulvestrant is currently licensed for use in
      postmenopausal women with hormone receptor positive advanced breast cancer which
      has progressed on prior endocrine therapy. As a pure oestrogen antagonist,
      fulvestrant avoids the risk of detrimental side effects of selective ER
      modulators such as tamoxifen, which has partial agonist activity. Fulvestrant,
      the only parenteral agent in this setting, has a good side effect profile and is
      well tolerated. Due to its unique mode of action, fulvestrant lacks cross
      resistance with existing agents. Fulvestrant is the subject of much ongoing
      research, which utilises knowledge of its novel mechanism and pharmacokinetic
      profile in order to optimise clinical efficacy and explore new roles, including
      first-line use in advanced breast cancer, use in combination with existing
      agents, in males, and in premenopausal women, and use as an adjuvant therapy.

PMID- 20156171
TI  - Recent insights into the biosynthesis and biological activities of natural
      xanthones.
AB  - This review focuses on recent advances in our understanding of the complex
      biosynthetic pathways and diverse biological activities of naturally occurring
      xanthones. The biosynthesis section covers studies published from 1989 to 2008 on
      xanthone production in plants and fungi, while the bioactivity review presents
      tabulated activities of more than 250 xanthones described in studies published
      from 2001 to 2008, together with structural information and indications of their
      wide-ranging potential uses as pharmacological tools. A large number of relevant
      papers have been published on these subjects (128 cited here), illustrating the
      diversity of the xanthones and their possible uses.

PMID- 20156172
TI  - Pediatric idiopathic nephrotic syndrome: treatment strategies in steroid
      dependent and steroid resistant forms.
AB  - Idiopathic nephrotic syndrome (INS) is defined as massive proteinuria and
      hypoalbuminemia associated with dyslipidemia and generalized oedema in most
      cases. It is thought to be due to a plasma factor of immunologic origin. Most
      cases are steroid responsive. However, a considerable proportion of children run
      a steroid dependent course. Calcineurin inhibitors and alkylating agents have
      been classical treatment strategies for such cases, but specific toxicity limits
      the use of these drugs. Mycophenolate mofetil (MMF) is an inhibitor of inosine
      monophosphate dehydrogenase and thus de novo purine synthesis. Several
      uncontrolled clinical trials have demonstrated the efficacy of MMF in steroid
      dependent NS with or without prior use of CyP and in children with nephrotoxicity
      due to prolonged CyA treatment. Non-compliance to steroid therapy can be
      responsible for multiple relapses and may be misinterpreted as steroid dependency
      and may therefore lead to unjustified increase of immunosuppressive treatment.
      Triamcinolone acetonide, a long acting steroid for intramuscular injection, can
      replace the usual oral prednisone treatment if non-compliance is suspected.
      Whereas the treatment of the primary course of INS is well established, steroid
      dependent and steroid resistant forms are still a challenge for pediatric
      nephrologists. Both under-treatment with multiple relapses with disease or
      steroid associated morbidity on the one hand and over-treatment with specific
      side effects of immunosuppressive drugs may have severe consequences for the
      patients.

PMID- 20156173
TI  - Homodimeric enzymes as drug targets.
AB  - Many enzymes and proteins are regulated by their quaternary structure and/or by
      their association in homo- and/or hetero-oligomer complexes. Thus, these protein
      protein interactions can be good targets for blocking or modulating protein
      function therapeutically. The large number of oligomeric structures in the
      Protein Data Bank (http://www.rcsb.org/) reflects growing interest in proteins
      that function as multimeric complexes. In this review, we consider the particular
      case of homodimeric enzymes as drug targets. There is intense interest in drugs
      that inhibit dimerization of a functionally obligate homodimeric enzyme. Because
      amino acid conservation within enzyme interfaces is often low compared to
      conservation in active sites, it may be easier to achieve drugs that target
      protein interfaces selectively and specifically. Two main types of dimerization
      inhibitors have been developed: peptides or peptidomimetics based on sequences
      involved in protein-protein interactions, and small molecules that act at hot
      spots in protein-protein interfaces. Examples include inhibitors of HIV protease
      and HIV integrase. Studying the mechanisms of action and locating the binding
      sites of such inhibitors requires different techniques for different proteins.
      For some enzymes, ligand binding is only detectable in vivo or after unfolding of
      the complexes. Here, we review the structural features of dimeric enzymes and
      give examples of inhibition through interference in dimer stability. Several
      techniques for studying these complex phenomena will be presented.

PMID- 20156174
TI  - Natural polyphenols that display anticancer properties through inhibition of
      kinase activity.
AB  - Over eleven hundred publications reporting anticancer activities of polyphenols
      have appeared in the peer-reviewed literature. In addition, a search of the
      PubMed database using "polyphenols - cancer - review" as keywords produced over
      320 hits for review articles (July 2009). Polyphenol anticancer activities
      include, among others, anti-oxidative, pro-apoptotic, DNA damaging, anti
      angiogenic, and immunostimulatory effects. Targeting specific protein kinases to
      combat cancer represents a major focus of oncology research within the so-called
      targeted therapy approach. An exhaustive search of the PubMed database (July
      2009) using "polyphenols - cancer - kinases" as keywords resulted in more than
      130 hits, half of them having been published within the past five years.
      Furthermore, the PubMed database contains 25 reviews on the subject of anti
      kinase activity of some specific polyphenols, including mainly curcumin and the
      green tea polyphenol (-)-epigallocatechin 3-gallate (EGCG). However, no attempt
      has been made yet to review this area of research in a comprehensive, general
      manner. The current review therefore aims to highlight those anticancer
      polyphenols that target specific kinases in various types of cancer. The present
      review also provides an in-depth analysis of polyphenol structure- activity
      relationships in relation to their anticancer activities and specific kinase
      targeting. Lastly, a number of polyphenols are identified as potential antitumor
      agents that could be used to combat biologically aggressive cancers, including
      metastasizing cancers, through the targeting of specific kinases.

PMID- 20156175
TI  - The Bcl-2 family as a rational target for the treatment of B-cell chronic
      lymphocytic leukaemia.
AB  - B-cell chronic lymphocytic leukaemia (B-CLL) is the most common lymphoid
      malignancy in the Western world, characterized by clonal growth and accumulation
      of monoclonal CD5+ B-cells in peripheral blood, bone marrow and peripheral
      lymphoid organs. Although the clinical course in B-CLL patients is highly
      variable, the most conserved feature is the prolonged survival of malignant B
      cells, which has been associated to defects in the apoptotic machinery. The
      apoptosis defects are mainly determined by a defective balance among pro- and
      anti-apoptotic members of the Bcl-2 family, often related to resistance of CLL B
      cells to chemotherapy. Purine nucleoside analogs or alkylating agents, alone or
      in combination, are the first-line treatment for B-CLL patients. Alternative,
      more specifically tailored therapeutics have been developed in recent years,
      including humanized monoclonal antibodies and kinase inhibitors. Here we shall
      review the drugs which are commonly used or are currently being assessed in
      clinical trials on B-CLL patients, their chemical structure, mechanisms of
      action, pharmacological properties, molecular targets, clinical efficacy and side
      effects, with a focus on drugs designed to promote apoptosis of malignant B-cells
      by targeting the Bcl-2 family.

PMID- 20156176
TI  - Recents patents for isolating, delivering and tracking adult stem cells in
      regenerative medicine.
AB  - The field of regenerative medicine offers nowadays the potential to significantly
      impact a wide spectrum of healthcare issues, from insulin-dependent diabetes
      mellitus (Type 1 diabetes, T1D) to cardiovascular disease. In tissue engineering
      biomaterials, biological factors, regeneration competent cells are used in the
      process of creating functional tissue. Regarding the type of stem or progenitor
      cells which represents the best candidate for therapy, embryonic stem cells have
      been considered the master cells capable of differentiating into every type of
      cells either in vitro or in vivo, in spite of serious ethical concerns.
      Nevertheless experimental evidence suggests that adult stem cells and even
      terminally differentiated somatic cells under appropriate microenvironmental
      treatments can be reprogrammed and contribute to a much wider spectrum of
      differentiated progeny than previously anticipated. One of the main goals is to
      exploit novel technologies aiming to isolate, expand and enrich sources of
      regeneration competent cells, especially adult somatic stem cells. Researchers
      are also trying to develop innovative strategies for effectively delivering
      regenerative cell populations and to implement 'tracking' tools to verify their
      engraftment and destiny in vivo. Here we review recent patents on the field
      issued over the past five years.

PMID- 20156177
TI  - Chronopharmaceutics: a promising drug delivery finding of the last two decades.
AB  - Pulsatile drug delivery system capable of releasing the drug after a
      predetermined lag period in pulsed or controlled release manner recently has
      drawn the attention of both academic and industrial research. Depending on the
      effective therapeutic application of the drug, a variety of design strategies
      have been formulated in the pursuit of pulsatile release. Circadian (24 hr cycle)
      dependency of various physiological and pathological functions is well
      established, thus, it becomes imperative to develop a drug delivery system to
      achieve release of drug at specific site and time. Such systems are advantageous
      for drugs which have an extensive first pass metabolism, biological tolerance,
      needs targeting of locally absorbed / active drug to a specific site in intestine
      and are useful for the therapy for chronopharmacological needs. This manuscript
      portrays the important patents related to chronomodulated release system such as
      system with eroding, rupturing or soluble barrier coatings. In addition, recently
      developed chronotherapeutic dosage forms including tablets, capsules, pellets,
      beads implants, osmotic pump, liposome, thermoresponsive, inflammation stimuli
      sensitive, electrical stimuli sensitive, ultrasound stimuli responsive, magnetic
      stimuli responsive etc., are also conferred.

PMID- 20156178
TI  - Patented bioavailability enhancement techniques of silymarin.
AB  - The present article dwells in reviewing critically the patents published mainly
      on the new emerging trends and techniques for increasing the bioavailability of
      silymarin, the polyphenolic fraction obtained from the seeds of Silybum marianum.
      The use of this herb for treating various ailments like hepatitis, cirrhosis,
      jaundice, mushroom and toxin poisoning is well known. But the potential use of
      this herbal drug is limited due to the poor absorption and poor bioavailability
      after oral administration The belief that the natural medicines are much safer
      than synthetic drugs, has gained popularity in recent years and led to tremendous
      growth of phytopharmaceutical usage and thus the need of improving the
      bioavailability by various means like complexation, derivatization,
      solubilization, targeted delivery, controlled delivery and many other
      miscellaneous techniques.

PMID- 20156179
TI  - Therapy Of XDR TB with thioridazine a drug beyond patent protection but eligible
      for patent "as new use".
AB  - Mycobacterium tuberculosis that is resistant to Isoniazid (INH) and Rifampin
      (Rif) and hence, multi-drug resistant (MDR) has progressed to extensive drug
      resistant (XDR) status. XDR strains of Mycobacterium tuberculosis (XDR Mtb) are
      resistant, in addition to INH and Rif, to any fluoroquinolone, streptomycin and
      to any of the injectable anti-TB drugs kanamycin, amikacin and capreomycin.
      Therapy of the XDR TB patient, even under the best conditions, is problematic and
      at least 20% of XDR TB patients die within one year after diagnosis. Mortality
      among XDR TB patients co-infected with HIV or presenting with AIDS is
      considerably higher reaching levels of 80% or higher. Drugs that are to prove
      effective against XDR Mtb must be able to reach the organism at the site where it
      mainly resides-the pulmonary macrophage. However, experience tells us that no
      matter how effective a drug may be, it will be followed by resistance. We have
      been able to demonstrate that thioridazine, a neuroleptic in safe use for over
      forty years, enhances the killing of phagocytosed Mycobacterium tuberculosis
      regardless of its antibiotic susceptibility profile and cure the mouse of a
      Mycobacterium tuberculosis pulmonary infection. Most recently, others have
      employed our studies for the therapy of the XDR TB patient with thioridazine and
      cured 10 out of 12 XDR TB patients of an XDR Mtb infection. Although thioridazine
      is beyond patent protection, its use for the therapy of XDR TB is new and
      therefore, a patent may be sought for "use as an anti-XDR TB agent".

PMID- 20156180
TI  - The challenges of RSV vaccines. Where do we stand?
AB  - The most realistic way to control RSV infection would be the development of an
      effective and safe vaccine. A formalin-inactivated RSV vaccine was evaluated in
      infants and children in the 1960's which disappointingly was linked with
      aggravation of RSV disease following the natural infection. Two candidate
      vaccines with purified protein F, have been tested, in humans and have been
      considered safe and somewhat immunogenic in seropositive persons providing
      different levels of protection against RSV re-infection. Live attenuated RSV
      vaccines induce local and systemic immunity without producing enhanced disease
      upon exposure of the vaccinee to the wild virus. Plasmid DNA vaccines were also
      evaluated in mice and elicited balanced systemic and pulmonary Th1/Th2 response
      without inducing an atypical pulmonary inflammatory reaction following the RSV
      challenge in cotton rats. Gene gun vaccination, a method to overcome the problem
      of DNA quantity, has been associated with a Th-2 biased response. Recent patents,
      such as plant vaccines, combined vaccines, attempted to invent new techniques for
      the generation of safe and effective vaccines. The new RSV vaccines should
      overcome many obstacles before being established as effective vaccines for the
      control of RSV infections especially for the young infants who are more
      susceptible to the virus.

PMID- 20156181
TI  - Impact of ultrasound contrast agents in echocardiographic assessment of ischemic
      heart disease.
AB  - Contrast echocardiography is a safe, accurate, and reproducible method to assess
      left ventricular volumes and function. Based on current guidelines, ultrasound
      contrast is indicated for left ventricular opacification at rest in patients with
      suboptimal echocardiographic images, and in stress echocardiography when >or= 2
      adjacent segments are poorly visualised. Adding contrast for assessment of
      regional myocardial perfusion expands the use of echocardiography in ischemic
      heart disease from detection of left ventricular dysfunction at rest or during
      stress to assessment of myocardial ischemia, extent of myocardial necrosis and re
      flow after coronary revascularisation. Myocardial perfusion also adds prognostic
      information to that given by structural and functional assessment alone and may
      reduce the need for more time consuming, expensive cardiac imaging procedures
      associated with radiation as well as coronary angiography with the risk of
      vascular complications. This article gives an overview of ultrasound contrast
      agents and their impact on echocardiographic assessment of ischemic heart disease
      also discussing recent patents.

PMID- 20156182
TI  - Design, synthesis and preliminary activity evaluation of novel L-lysine
      derivatives as aminopeptidase N/CD13 inhibitors.
AB  - A novel class of L-lysine derivatives as aminopeptidase N (APN) inhibitors was
      designed and synthesized. Activity evaluation showed that compound C7 (IC(50) =
      9.6 +/-1.3 microM) and C20 (IC(50) = 13.6 +/- 1.9 microM) were equivalent to the
      positive control Bestatin (IC(50) = 11.3 +/- 1.6 microM).

PMID- 20156183
TI  - Oyster mushroom laccase inhibits hepatitis C virus entry into peripheral blood
      cells and hepatoma cells.
AB  - There is no protective vaccine or effective drug against hepatitis C virus (HCV).
      Sustained virological response to INF/ribavirin treatment regimen has an
      efficiency of about 50%. Many patients worldwide have used traditional medicines
      and herbal medicine in particular. A laccase has been purified from oyster
      mushroom (Pleurotus ostreatus) to homogeneity by DEAE Affi-gel blue gel, CM
      Sephadex G-50 and Sephadex G-100. The molecular weight of the laccase was about
      58 kDa in SDS-PAGE. The optimum pH and temperature of the laccase activity were
      pH 4.0 and 60 degrees C, respectively. The activity of the enzyme increased
      steadily from 20 to 40 degrees C, then very slowly from 40 degrees to 60 degrees
      C, while the enzyme activity decreased to 9% at 90 degrees C. The activity of the
      laccase changed gradually over the pH range 2.0-4.0. However, the enzyme activity
      was totally abrogated at the pH 8 and above. Incubation of peripheral blood cells
      PBCs and hepatoma HepG2 cells with laccase which were then infected with HCV did
      not protect the cells from HCV attack and entry, while direct interaction between
      HCV and the laccase at the concentrations of 2.0 and 2.5 mg/ml led to a complete
      inhibition of virus entry after seven days of incubation. Meantime, the laccase
      at the concentrations of 1.0 and 1.5 mg/ml did not display any blocking activity.
      The potential activity of the laccase on intracellular HCV replication in
      infected HepG2 cells has been examined. The laccase was capable of inhibiting HCV
      replication at the concentrations of 1.25 and 1.5 mg/ml after first dose of
      treatment for four days and at the concentrations of 0.75, 1.0, 1.25 and 1.5
      mg/ml after the second dose of treatment for another four days.

PMID- 20156184
TI  - Production of active MMP7 in E. coli and its application for metalloproteinase
      inhibitors screening.
AB  - MMP-7 is the smallest metalloproteinase. Its unregulated activities and existence
      in serum are recently known to be tightly related with life-threatening disease
      such as cardiac disease and several cancers. The protein production is thought to
      be useful for its characterization and antibody generation. Although many
      attempts at bacterial expressions have been conducted, they were recovered as
      insoluble and inactive protein. In this study, after soluble expression, single
      step purification and conversion to active protease, it was applied for the
      screening secretory metalloproteinase inhibitors in conditioned media of human
      cancer cells.

PMID- 20156185
TI  - Determination of proteins induced in response to jasmonic acid and salicylic acid
      in resistant and susceptible cultivars of tomato.
AB  - Jasmonic acid (JA) and salicylic acid (SA) are signaling molecules that play key
      roles in the regulation of metabolic processes, reproduction, and defense against
      pathogens. The proteomics approach was used to identify proteins that are induced
      by JA and SA in the tomato cultivars Roma and Pant Bahr, which are susceptible
      and resistant to bacterial wilt, respectively. Threonine deaminase and leucine
      amino peptidase were upregulated, and ribulose-1,5-bisphosphate
      carboxylase/oxygenase small chain was downregulated by time-course application of
      JA. Translationally controlled tumor protein was upregulated by time-course
      application of SA. Protein disulfide isomerase was upregulated by application of
      either JA or SA. Proteins related to defense, energy, and protein
      destination/storage are suspected to be responsible for the susceptibility or
      resistance of the cultivars. Furthermore, in Roma, iron ABC transporter was
      upregulated by JA and down-regulated by SA. Iron ABC transporter plays a part in
      the signal transduction of both JA and SA in cultivars of tomato that are
      resistant to bacterial wilt.

PMID- 20156186
TI  - Binding of reactive brilliant red to human serum albumin: insights into the
      molecular toxicity of sulfonic azo dyes.
AB  - The non-covalent interaction of reactive brilliant red (RBR) as a representative
      of sulfonic azo compounds with human serum albumin (HSA) was investigated by a
      combination of UV-VIS spectrometry, fluorophotometry, circular dichroism (CD) and
      isothermal titration calorimetry (ITC) technique. The thermodynamic
      characterization of the interaction was performed. The saturation binding numbers
      of RBR on peptide chains were determined and the effects of electrolytes and
      temperature were investigated. The ionic interaction induced a combination of
      multiple non-covalent bonds including hydrogen bonds, hydrophobic interactions
      and van der Waals force. A three-step binding model of RBR was revealed. The
      binding of RBR molecules might occur on the external surface of HSA via electric
      interaction when the mole ratio of RBR to HSA was less than 40 and RBR molecules
      entered the hydrophobic intracavity of HSA when ratio was more than 40. Moreover,
      RBR binding resulted in a conformational change in the structure of HSA or even
      the precipitation of HSA and inhibited its function accordingly. The possible
      binding site and the conformational transition of HSA were hypothesized and
      illustrated. This work provides a new insight into non-covalent interactions
      between sulfonic azo compounds and proteins, which may be further used to
      investigate the potential toxicity mechanism of azo dyes.

PMID- 20156187
TI  - Circular dichroism studies on the Deinococcus radiodurans Nudix hydrolase
      DR_0079: an atypical thermal melt.
AB  - The crystal structure for the Deinococcus radiodurans Nudix protein DR_0079 was
      recently determined in the metal-free form at 1.9 A resolution (2O5F). The
      protein adopts the fundamental fold common to the Nudix family of proteins, a
      large mixed b-sheet sandwiched between the a-helix of the "Nudix box" and a
      second a-helix. The protein's physical properties were further characterized by
      circular dichroism (CD) spectroscopy. A CD thermal melt at 220 nm identifies an
      inflection point at approximately 52 degrees C. However, unlike typical CD
      thermal melts, the negative ellipticity at 220 nm becomes more negative upon
      passing through the inflection point. Both NMR spectroscopy and size exclusion
      chromatography indicate that heating effects the irreversible formation of a
      large molecular weight complex. After cooling, the negative ellipiticity at 220
      nm increases further, and overall, the CD spectrum at 25 degrees C suggests that
      heat-treated DR_0079 has more a-helical and b-sheet structure than non-heat
      treated DR_0079.

PMID- 20156188
TI  - Salmonella as live trojan horse for vaccine development and cancer gene therapy.
AB  - The design of efficient vectors for vaccine development and cancer gene therapy
      is an area of intensive research. Bacteria-based vectors are being investigated
      as optimal vehicles for antigen and therapeutic gene delivery to immune and
      tumour cells. Attenuated Salmonella strains have shown great potential as live
      vectors with broad applications in human and veterinary medicine. An impressively
      high, and still growing, number of reports published over the last two decades
      have demonstrated the effectiveness in animal models of Salmonella-based
      therapies for the prevention and treatment of infectious and non-infectious
      diseases, as well as cancer. Further, the recent dramatic expansion in knowledge
      of genetics, biology and pathogenesis of the bacteria allows more rational design
      of Salmonella constructs tailored for specific applications. However, only few
      clinical trials have been conducted so far, and although they have conclusively
      demonstrated the safety of this system, the results on immunogenicity are less
      than optimal. Thus, more research particularly in target species is required to
      bring this system closer to human and veterinary use. In this review we first
      describe some particularities of the bacteria and its relationship with the host
      that could be on the basis of its success as vector, and then summarize the
      different strategies used so far to develop Salmonella-based vaccines for
      infectious diseases as well as for non-traditional indications such as prion and
      Alzheimer disease vaccination. Finally, we review the many different approaches
      that employ Salmonella for the design of new therapies for cancer.

PMID- 20156189
TI  - Lactococcus lactis as a cell factory for delivery of therapeutic proteins.
AB  - The food-grade bacterium Lactococcus lactis has been extensively investigated
      during the last two decades as a delivery vector for therapeutic proteins, DNA
      and vaccine antigens. The bacterium represents a safe, genetically tractable
      vector capable of producing heterologous therapeutic proteins at mucosal sites.
      Here we review recent work in which recombinant L. lactis strains have been
      exploited as agents to treat inflammatory bowel disease, allergy and cancer. We
      also describe the ability of L. lactis to deliver proteins with adjuvant
      potential, vaccines and DNA and discuss the therapeutic possibilities of this
      approach.

PMID- 20156190
TI  - Engineered E. coli as vehicles for targeted therapeutics.
AB  - Improving the means of drug delivery has become an important field of
      pharmaceutical research. The development of safe and advanced vectors for gene
      therapy and other novel therapies will allow for targeted delivery of
      pharmaceutically active agents and carries promise to improve therapies both
      through increased efficiency (e.g. improved cellular uptake of the active drug)
      as well as lower toxicity (e.g. through targeted delivery only to the cells
      requiring treatment) for a large number of pharmaceutical agents. Here we are
      reviewing the nascent field using live bacteria as vectors for therapeutic and
      preventive agents in a wide range of areas, from vaccine purposes to gene therapy
      and delivery of therapeutic RNA interference. This review focuses particularly on
      the use of E. coli derived strains for therapeutic delivery.

PMID- 20156191
TI  - Tumour targeting with systemically administered bacteria.
AB  - Challenges for oncology practitioners and researchers include specific treatment
      and detection of tumours. The ideal anti-cancer therapy would selectively
      eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria
      have emerged as biological gene vectors with natural tumour specificity, capable
      of homing to tumours and replicating locally to high levels when systemically
      administered. This property enables targeting of both the primary tumour and
      secondary metastases. In the case of invasive pathogenic species, this targeting
      strategy can be used to deliver genes intracellularly for tumour cell expression,
      while non-invasive species transformed with plasmids suitable for bacterial
      expression of heterologous genes can secrete therapeutic proteins locally within
      the tumour environment (cell therapy approach). Many bacterial genera have been
      demonstrated to localise to and replicate to high levels within tumour tissue
      when intravenously (IV) administered in rodent models and reporter gene tagging
      of bacteria has permitted real-time visualisation of this phenomenon. Live
      imaging of tumour colonising bacteria also presents diagnostic potential for this
      approach. The nature of tumour selective bacterial colonisation appears to be
      tumour origin- and bacterial species- independent. While originally a correlation
      was drawn between anaerobic bacterial colonisation and the hypoxic nature of
      solid tumours, it is recently becoming apparent that other elements of the unique
      microenvironment within solid tumours, including aberrant neovasculature and
      local immune suppression, may be responsible. Here, we consider the pre-clinical
      data supporting the use of bacteria as a tumour-targeting tool, recent advances
      in the area, and future work required to develop it into a beneficial clinical
      tool.

PMID- 20156192
TI  - Protein translocation through the Sec61/SecY channel.
AB  - Special codes are embedded in the primary sequence of newly synthesized proteins
      to determine their final destination. Protein translocation across biological
      membranes requires co-operation between the targeting and translocation
      machineries. A conserved membrane channel, the Sec61/SecY complex, mediates
      protein translocation across or integration into the endoplasmic reticulum
      membrane in eukaryotes and the plasma membrane in prokaryotes. A combination of
      recent biochemical and structural data provides novel insights into the mechanism
      of how the channel allows polypeptide movement into the exoplasmic space and the
      lipid bilayer.

PMID- 20156193
TI  - Commonly used tag combinations for tandem affinity purification.
AB  - TAP (tandem affinity purification) allows rapid and clean isolation of a tagged
      protein along with its interacting partners from cell lysates. Initially
      developed in yeast, the TAP method has subsequently been adapted to other cells
      and organisms. In combination with MS analysis, this method has become an
      indispensable tool for systematic identification of target-associated protein
      complexes. The key feature of TAP is the use of a dual-affinity tag, which is
      fused to the protein of interest. The original TAP tag consisted of two IgG
      binding units of Protein A of Staphylococcus aureus and the calmodulin-binding
      peptide. As the technique has been widely exploited, a number of alternative TAP
      tags based on other affinity handles have been developed. The present review
      gives an overview of the various tag combinations for TAP with a highlight on
      those alternatives that result in improved yields or unique features. The
      information provided should assist in the selection and development of TAP tags
      for specific applications.

PMID- 20156194
TI  - Filamin associates with stress signalling kinases MKK7 and MKK4 and regulates JNK
      activation.
AB  - SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase) belongs to the
      MAPK (mitogen-activated protein kinase) family and is important in many
      biological contexts. JNK activation is regulated by phosphorylation of specific
      tyrosine and threonine residues sequentially catalysed by MKK4 and MKK7, which
      are both dual-specificity MAPKKs (MAPK kinases). Previously, we reported that
      tyrosine-phosphorylation of JNK by MKK4 precedes threonine-phosphorylation by
      MKK7, and that both are required for synergistic JNK activation. In the present
      study, we identify the actin-binding protein-280 (Filamin A) as a presumed
      'binder' protein that can bind to MKK7, as well as to MKK4, connecting them in
      close proximity. We show that Filamin family members A, B and C interact with
      MKK4 and MKK7, but not with JNK. Filamin A binds to an N-terminal region
      (residues 31-60) present in the MKK7gamma and MKK7beta splice isoforms, but
      cannot bind to MKK7alpha which lacks these amino acids. This same N-terminal
      region is crucial for the intracellular co-localization of MKK7gamma with actin
      stress fibres and Filamin A. Experiments using Filamin-A-deletion mutants
      revealed that the MKK7-binding region of Filamin A differs from its MKK4-binding
      region, and that MKK7gamma (but not MKK7alpha) can form a complex with Filamin A
      and MKK4. Finally, we used Filamin-A-deficient cells to show that Filamin A
      enhances MKK7 activation and is important for synergistic stress-induced JNK
      activation in vivo. Thus Filamin A is a novel member of the group of scaffold
      proteins whose function is to link two MAPKKs together and promote JNK
      activation.

PMID- 20156195
TI  - Genomic organization and regulation of the human orexin (hypocretin) receptor 2
      gene: identification of alternative promoters.
AB  - Orexins (hypocretins), acting via their receptors, are involved in the control of
      feeding behaviour, sleep, arousal and energy homoeostasis. However, regulation of
      the human orexin receptor 2 (hOX2R) gene remains unknown. We have identified four
      transcripts arising from alternative splicing from three exons. These exon 1
      variants were designated exons 1A, 1B and 1C on the basis of their 5'-3' order.
      RT (reverse transcription)-PCR demonstrates the differential expression in
      various human tissues. The alternative 5'-UTRs (untranslated regions) possessed
      by these isoforms have different translational efficiencies, which regulate the
      level of protein expression. In the present study, we have demonstrated that the
      hOX2R gene is regulated by two promoters and the novel transcripts are regulated
      by the distal promoter located upstream of exon 1A. We have demonstrated that the
      AP-1 (activator protein 1) motif is critical for sustaining the basal activity of
      distal promoter. Analysis of the proximal promoter revealed the region regulating
      promoter activity contained putative binding elements including those for CREB
      (cAMP-response-element-binding protein), GATA-2 and Oct-1. Using the chromatin
      immunoprecipitation assay, we demonstrated that CREB, GATA-2 and Oct-1
      transcription factors bind to these critical regulatory promoter elements.
      Mutational studies suggested that these motifs functioned independently, but have
      a compound effect regulating hOX2R gene transcription. Furthermore, proximal
      promoter activity is enhanced by both PKA (protein kinase A) and PKC (protein
      kinase C) pathway activation, via binding of CREB and GATA-2 transcription
      factors. In conclusion, we have demonstrated that expression of hOX2R is
      regulated by a complex involving a proximal PKA/PKC-regulated promoter and a
      distal promoter regulating tissue-specific expression of alternative transcripts
      which in turn post-transcriptionally regulate receptor levels.

PMID- 20156196
TI  - Transglutaminase-2: a new endostatin partner in the extracellular matrix of
      endothelial cells.
AB  - Endostatin, a C-terminal fragment of collagen XVIII, binds to TG-2
      (transglutaminase-2) in a cation-dependent manner. Recombinant human endostatin
      binds to TG-2 with an affinity in the nanomolar range (Kd=6.8 nM). Enzymatic
      assays indicated that, in contrast with other extracellular matrix proteins,
      endostatin is not a glutaminyl substrate of TG-2 and is not cross-linked to
      itself by the enzyme. Two arginine residues of endostatin, Arg27 and Arg139, are
      crucial for its binding to TG-2. They are also involved in the binding to heparin
      [Sasaki, Larsson, Kreuger, Salmivirta, Claesson-Welsh, Lindahl, Hohenester and
      Timpl (1999) EMBO J. 18, 6240-6248], and to alpha5beta1 and alphavbeta3 integrins
      [Faye, Moreau, Chautard, Jetne, Fukai, Ruggiero, Humphries, Olsen and Ricard-Blum
      (2009) J. Biol. Chem. 284, 22029-22040], suggesting that endostatin is not able
      to interact simultaneously with TG-2 and heparan sulfate, or with TG-2 and
      integrins. Inhibition experiments support the hypothesis that the GTP-binding
      site of TG-2 is a potential binding site for endostatin. Endostatin and TG-2 are
      co-localized in the extracellular matrix secreted by endothelial cells under
      hypoxia, which stimulates angiogenesis. This interaction, occurring in a cellular
      context, might participate in the concerted regulation of angiogenesis and
      tumorigenesis by the two proteins.

PMID- 20156197
TI  - Effect of VEGF (vascular endothelial growth factor) on expression of IL-8
      (interleukin-8), IL-1beta and their receptors in bovine theca cells.
AB  - Cytokines such as VEGF (vascular endothelial growth factor) and ILs
      (interleukins) are involved in follicular development in the mammalian ovary. The
      aim of the present study is to examine the transcripts of IL-8 and -1 that differ
      during follicular development; the relationships between IL-8, IL-1 and VEGF in
      theca cells is still unknown. We first examined the gene expression of IL-8, IL
      1beta and their respective receptors, CXCR1 and IL-1R1 in the theca cells of PRF
      (preselection) and POF (postselection follicles) from the bovine ovary.
      Expression of IL-8 and CXCR1 genes were observed in POF, whereas expression of IL
      1beta and IL-1R1 genes was observed in both follicles. Secondly, we examined the
      effects of VEGF on the expression of IL-8, IL-1beta and their receptors genes in
      cultured bovine theca cells. mRNA expression was quantified by using real-time
      PCR methods. VEGF stimulates the expression of IL-8 and CXCR1 mRNA. However, VEGF
      down-regulates the expression of CXCR2 mRNA during the culture period. Expression
      of IL-1beta and -1R1 mRNA was induced in the cultured theca cells at 48 h. Our
      data demonstrate that VEGF stimulated the expression of the IL-8 and CXCR1 genes
      and that CXCR2 expression was suppressed by VEGF, suggesting a follicle stage
      dependent expression pattern for the IL-8 system. Furthermore, our results
      suggest that the transcription system for CXCR genes may have different pathways
      of VEGF stimulation in bovine theca cells. Taken together, our data suggested
      that VEGF is associated with the IL system in theca cells in bovine ovary.

PMID- 20156199
TI  - Proteolytic processing of an Arabidopsis membrane-bound NAC transcription factor
      is triggered by cold-induced changes in membrane fluidity.
AB  - Changes in membrane fluidity are the earliest cellular events that occur in plant
      cells upon exposure to cold. This subsequently triggers physiological processes,
      such as calcium influx and reorganization of actin cytoskeletons, and induces
      expression of cold-responsive genes. The plasma-membrane-anchored NAC
      (NAM/ATAF/CUC) transcription factor NTL6 is of particular interest. Cold triggers
      proteolytic activation of the dormant NTL6 protein, which in turn elicits
      pathogen-resistance responses by inducing a small group of cold-inducible PR
      (pathogenesis-related) genes in Arabidopsis. In the present study, we show that
      proteolytic processing of NTL6 is regulated by cold-induced remodelling of
      membrane fluidity. NTL6 processing was stimulated rapidly by cold. The protein
      stability of NTL6 was also enhanced by cold. The effects of cold on NTL6
      processing and protein stability were significantly reduced in cold-acclimatized
      plants, supporting the regulation of NTL6 processing by membrane fluidity.
      Consistent with this, although NTL6 processing was stimulated by pharmacological
      agents that reduce membrane fluidity and thus mimic cold, it was inhibited when
      plants were treated with a 18:3 unsaturated fatty acid, linolenic acid. In
      addition, the pattern of NTL6 processing was changed in Arabidopsis mutants with
      altered membrane lipid compositions. Assays employing chemicals that inhibit
      activities of the proteasome and proteases showed that NTL6 processing occurs via
      the regulated intramembrane proteolysis mechanism. Interestingly, a
      metalloprotease inhibitor blocked the NTL6 processing. These observations
      indicate that a metalloprotease activity is responsible for NTL6 processing in
      response to cold-induced changes in membrane fluidity.

PMID- 20156198
TI  - Isolation and characterization of selective and potent human Fab inhibitors
      directed to the active-site region of the two-component NS2B-NS3 proteinase of
      West Nile virus.
AB  - There is a need to develop inhibitors of mosquito-borne flaviviruses, including
      WNV (West Nile virus). In the present paper, we describe a novel and efficient
      recombinant-antibody technology that led us to the isolation of inhibitory high
      affinity human antibodies to the active-site region of a viral proteinase. As a
      proof-of-principal, we have successfully used this technology and the synthetic
      naive human combinatorial antibody library HuCAL GOLD(R) to isolate selective and
      potent function-blocking active-site-targeting antibodies to the two-component
      WNV NS (non-structural protein) 2B-NS3 serine proteinase, the only proteinase
      encoded by the flaviviral genome. First, we used the wild-type enzyme in antibody
      screens. Next, the positive antibody clones were counter-screened using an NS2B
      NS3 mutant with a single mutation of the catalytically essential active-site
      histidine residue. The specificity of the antibodies to the active site was
      confirmed by substrate-cleavage reactions and also by using proteinase mutants
      with additional single amino-acid substitutions in the active-site region. The
      selected WNV antibodies did not recognize the structurally similar viral
      proteinases from Dengue virus type 2 and hepatitis C virus, and human serine
      proteinases. Because of their high selectivity and affinity, the identified human
      antibodies are attractive reagents for both further mutagenesis and structure
      based optimization and, in addition, for studies of NS2B-NS3 activity.
      Conceptually, it is likely that the generic technology reported in the present
      paper will be useful for the generation of active-site-specific antibody probes
      for multiple enzymes.

PMID- 20156200
TI  - Visual outcomes of treated periocular capillary haemangiomas in childhood: a 10
      year review.
AB  - PURPOSE: To report our experiences of treating periocular capillary haemangioma
      with particular emphasis on visual outcomes. METHODS: Patients who underwent
      treatment for periocular capillary haemangioma were identified, and a chart
      review was performed. RESULTS: There were seventeen patients in the study. The
      main indications for treatment were increased size of lesion with threat of
      amblyopia and partial or full pupil occlusion. Seven patients required more than
      one type of treatment. Fourteen patients had intralesional steroid treatment and
      six patients had oral steroids. Intralesional steroids gave variable results with
      minimal side-effects, oral steroids were very effective but 4 out of 6 patients
      developed side-effects. The average pretreatment astigmatism was 2.4D and post
      treatment this had reduced to 1.3D. Final visual outcomes were available for 15
      patients, 13 had visual acuity of 6/7.5 or better, two were amblyopic with vision
      of 6/9-2 and 6/18. CONCLUSION: In this study, intralesional steroids were used
      for localized lesions and oral steroids for diffuse haemangiomas with orbital
      involvement. Treatment especially with oral steroids was found to halt the
      proliferative phase and assist early haemangioma regression reducing ocular
      sequelae.

PMID- 20156201
TI  - Encircling band, laser retinopexy and lens removal as standard procedure in
      complicated retinal detachment shows a good clinical outcome.
AB  - PURPOSE: To evaluate vitrectomy in conjunction with the use of perfluorocarbon,
      cerclage, laser retinopexy, lens removal and silicone oil as surgical treatment
      of proliferative vitreoretinopathy associated with retinal detachment. METHODS:
      Sixty-two eyes of 62 patients were treated for complicated retinal detachment
      following failed prior scleral buckling. Outcome measures were; retinal
      reattachment rate 6 months after silicone oil removal, status of the retina,
      visual acuity (VA), duration of silicone tamponade and frequency of reoperations.
      RESULTS: The final reattachment rate was 95%. Reoperations had to be performed in
      25% of patients. Eighty-one per cent of these patients received one and 19% two
      or more operations following silicone oil implantation. The mean time to
      reoperation was 1.8 +/- 1.4 months. Silicone oil was removed after 5.6 +/- 4.1
      months following the last vitreoretinal procedure in 90%, respectively, 95% with
      attached retina. Five per cent experienced retinal detachment after silicone oil
      removal. At the end of follow-up, the mean VA was 0.13 +/- 0.26 Snellen. Seventy
      per cent of patients achieved a vision of 20/200 or better (mean 0.25 +/- 0.27).
      CONCLUSION: Our study demonstrates good final outcomes when a rigorous surgical
      approach was used. Furthermore, this standard procedure reduces the need for
      reoperations and consequently improves the functional outcome.

PMID- 20156202
TI  - Breakage of the haptic of a single-piece acrylic intraocular lens after
      transscleral fixation.

PMID- 20156203
TI  - Genes and behavior interact to determine mortality in mice when food is scarce
      and competition fierce.

PMID- 20156204
TI  - Dietary restriction affects lifespan but not cognitive aging in Drosophila
      melanogaster.
AB  - Dietary restriction extends lifespan in a wide variety of animals, including
      Drosophila, but its relationship to functional and cognitive aging is unclear.
      Here, we study the effects of dietary yeast content on fly performance in an
      aversive learning task (association between odor and mechanical shock). Learning
      performance declined at old age, but 50-day-old dietary-restricted flies learned
      as poorly as equal-aged flies maintained on yeast-rich diet, even though the
      former lived on average 9 days (14%) longer. Furthermore, at the middle age of 21
      days, flies on low-yeast diets showed poorer short-term (5 min) memory than flies
      on rich diet. In contrast, dietary restriction enhanced 60-min memory of young (5
      days old) flies. Thus, while dietary restriction had complex effects on learning
      performance in young to middle-aged flies, it did not attenuate aging-related
      decline of aversive learning performance. These results are consistent with the
      hypothesis that, in Drosophila, dietary restriction reduces mortality and thus
      leads to lifespan extension, but does not affect the rate with which somatic
      damage relevant for cognitive performance accumulates with age.

PMID- 20156205
TI  - Declining expression of a single epithelial cell-autonomous gene accelerates age
      related thymic involution.
AB  - Age-related thymic involution may be triggered by gene expression changes in
      lymphohematopoietic and/or nonhematopoietic thymic epithelial cells (TECs). The
      role of epithelial cell-autonomous gene FoxN1 may be involved in the process, but
      it is still a puzzle because of the shortage of evidence from gradual loss-of
      function and exogenous gain-of-function studies. Using our recently generated
      loxP-floxed-FoxN1(fx) mouse carrying the ubiquitous CreER(T) (uCreER(T))
      transgene with a low dose of spontaneous activation, which causes gradual FoxN1
      deletion with age, we found that the uCreER(T)-fx/fx mice showed an accelerated
      age-related thymic involution owing to progressive loss of FoxN1(+) TECs. The
      thymic aging phenotypes were clearly observable as early as at 3-6 months of age,
      resembling the naturally aged (18-22-month-old) murine thymus. By intrathymically
      supplying aged wild-type mice with exogenous FoxN1-cDNA, thymic involution and
      defective peripheral CD4(+) T-cell function could be partially rescued. The
      results support the notion that decline of a single epithelial cell-autonomous
      gene FoxN1 levels with age causes primary deterioration in TECs followed by
      impairment of the total postnatal thymic microenvironment, and potentially
      triggers age-related thymic involution in mice.

PMID- 20156206
TI  - DILP-producing median neurosecretory cells in the Drosophila brain mediate the
      response of lifespan to nutrition.
AB  - Dietary restriction extends lifespan in diverse organisms, but the gene
      regulatory mechanisms and tissues mediating the increased survival are still
      unclear. Studies in worms and flies have revealed a number of candidate
      mechanisms, including the target of rapamycin and insulin/IGF-like signalling
      (IIS) pathways and suggested a specific role for the nervous system in mediating
      the response. A pair of sensory neurons in Caenorhabditis elegans has been found
      to specifically mediate DR lifespan extension, but a neuronal focus in the
      Drosophila nervous system has not yet been identified. We have previously shown
      that reducing IIS via the partial ablation of median neurosecretory cells in the
      Drosophila adult brain, which produce three of the seven fly insulin-like
      peptides, extends lifespan. Here, we show that these cells are required to
      mediate the response of lifespan to full feeding in a yeast dilution DR regime
      and that they appear to do so by mechanisms that involve both altered IIS and
      other endocrine effects. We also present evidence of an interaction between these
      mNSCs, nutrition and sleep, further emphasising the functional homology between
      the DILP-producing neurosecretory cells in the Drosophila brain and the
      hypothalamus of mammals in their roles as integration sites of many inputs for
      the control of lifespan and behaviour.

PMID- 20156207
TI  - Pregnancy outcome in women with repaired versus unrepaired isolated ventricular
      septal defect.
AB  - OBJECTIVE: To compare the risks of pregnancy complications in women with repaired
      and unrepaired isolated ventricular septal defect (VSD). DESIGN: A retrospective
      multicentre study. SETTING: Tertiary centres in the Netherlands and Belgium.
      METHODS: Women were identified using two congenital heart disease registries.
      Eighty-eight women were identified who had experienced 202 pregnancies, including
      46 miscarriages and nine terminations of pregnancy. Information on each completed
      pregnancy (n = 147; unrepaired VSD, n = 104; repaired VSD, n = 43) was obtained
      using medical records and telephone interviews. Data from the Generation R
      database (prospective cohort study; n = 9667) were used to determine the
      background risk (controls). Odds ratios and 95% CI were estimated using general
      estimation equation analysis adjusted for multiple pregnancies per woman,
      maternal age and parity status. MAIN OUTCOME MEASURES: Adjusted odds ratios
      (AORs) for developing pregnancy complications in relation to corrective status.
      RESULTS: Pregnancies in women with an unrepaired VSD were associated with a
      higher risk of pre-eclampsia (AOR 4.59, 95% CI 2.01-10.5, P < 0.001) compared
      with controls. No differences were observed when comparing women with repaired
      VSD and controls. Pregnancies in women with repaired VSD were associated with a
      higher risk of premature labour (AOR 4.02, 95% CI 1.12-14.4, P = 0.03) and small
      for-gestational-age (SGA) births (AOR 4.09, 95% CI 1.27-13.2, P = 0.02) compared
      with women with unrepaired VSD. CONCLUSIONS: Women with unrepaired VSD are at
      increased risk of pre-eclampsia, which suggests that it is not a benign
      condition. In addition, women with repaired VSD are at increased risk of
      premature labour and SGA births compared with women with unrepaired VSD.

PMID- 20156209
TI  - The effect of hysterectomy or levonorgestrel-releasing intrauterine system on
      lower urinary tract symptoms: a 10-year follow-up study of a randomised trial.
AB  - OBJECTIVE: To evaluate the effect of hysterectomy and levonorgestrel-releasing
      intrauterine system (LNG-IUS) on lower urinary tract symptoms (LUTS) among women
      treated for menorrhagia. DESIGN: Randomised controlled trial analysed by actual
      treatment. SETTING: Five university hospitals in Finland. SAMPLE: A cohort of 236
      women, aged 35-49 years, referred for menorrhagia between 1994 and 1997. METHODS:
      Women were randomly assigned to treatment by hysterectomy (n = 117) or LNG-IUS (n
      = 119). MAIN OUTCOME MEASURES: Lower urinary tract symptoms were evaluated by
      questionnaires at baseline, and after 6, 12 months, 5, and 10 years. Medications
      and operations for urinary incontinence were confirmed from medical records and
      national registries. RESULTS: Overall, 221 (94%) women took part in the 10-year
      follow-up evaluation. As 55 (46%) women originally randomised to the LNG-IUS
      group underwent hysterectomy, the results were analysed by actual treatment.
      Women treated by hysterectomy used more medication for urinary incontinence than
      LNG-IUS users (12% versus 1%) (OR 9.45, 95% CI 1.24-71.87, P = 0.006). Three
      hysterectomised women and one LNG-IUS user underwent surgery for stress urinary
      incontinence (SUI). Women treated by hysterectomy had more urinary tract
      infections (UTIs) than LNG-IUS users (OR 3.20, 95% CI 1.47-6.96, P = 0.002).
      Feeling of incomplete emptying (OR 3.00, 95% CI 1.00-9.05, P = 0.04) and SUI (OR
      1.83, 95% CI 1.01-3.32, P = 0.04) were more common among women treated by
      hysterectomy. No differences between the study arms were noted in urge urinary
      incontinence or by the Urinary Incontinence Severity Score. A multivariate model
      showed that UTIs were associated with hysterectomy (P = 0.004). CONCLUSIONS:
      Hysterectomy increases the risks for incomplete emptying, lower UTIs and SUI.

PMID- 20156210
TI  - Increased risk of low birthweight and small for gestational age infants among
      women with tuberculosis.
AB  - OBJECTIVE: As the relationship between tuberculosis (TB) and fetal outcomes
      remains unclear, this study used a 3-year nationwide population-based data set to
      determine the risk of adverse pregnancy outcomes [low birthweight (LBW), preterm
      birth and small for gestational age (SGA) infants] among women with TB. DESIGN: A
      cross-sectional retrospective study. SETTING: Taiwan. SAMPLE: Linking the Taiwan
      birth certificate registry and the Taiwan National Health Insurance Research
      Dataset, we identified 761 women who gave birth from 2001 to 2003 and who had
      received medication treatment for TB during their pregnancy, together with 3805
      unaffected women matched in terms of age and year of delivery. METHODS:
      Conditional logistic regression analyses were performed to compare the risk of
      LBW, preterm birth and SGA for mothers with TB and unaffected mothers. MAIN
      OUTCOME MEASURES: The risk of LBW, preterm birth and SGA. RESULTS: Mothers
      diagnosed with TB had significantly higher percentages of LBW (8.5 versus 6.4%, P
      = 0.033) and SGA (19.7 versus 16.7%, P = 0.048) infants than unaffected mothers.
      However, there was no significant difference in preterm birth (8.0 versus 8.0%, P
      = 0.961) between these two groups. The adjusted odds ratios of having LBW and SGA
      infants for mothers with TB were 1.35 (95% CI = 1.01-1.81) and 1.22 (95% CI =
      1.00-1.49), respectively, compared with unaffected mothers. CONCLUSIONS: We
      concluded that women diagnosed with TB during pregnancy are at increased risk for
      having LBW and SGA babies, compared with unaffected mothers. We suggest that
      clinicians should make women with TB aware of the potential risks before planning
      a child.

PMID- 20156211
TI  - The volume perspective: a comparison of two excisional treatments for cervical
      intraepithelial neoplasia (laser versus LLETZ).
AB  - OBJECTIVE: To compare two excisional treatments, laser cone biopsy and large loop
      excision of the transformation zone (LLETZ), in terms of the volume of tissue
      removed, and to determine the relation between the height and the total volume of
      the cone specimen. DESIGN: Retrospective cross-sectional study. SETTING: Large
      teaching hospital in London. POPULATION: A total of 1136 eligible excisional
      treatments (laser cone or large loop excision of the transformation zone, LLETZ).
      METHODS: Eligible excisional treatments (laser cone or LLETZ) performed between 1
      January 2002 and 31 December 2007 in our colposcopy unit were identified using
      the Infoflex(R) database. The total volume of the cone biopsy was calculated
      mathematically using the data provided in the histopathology reports. MAIN
      OUTCOME MEASURES: The volume of the cone biopsy was compared with the technique
      of excision and the histology grades. RESULTS: Three hundred and thirty-nine
      laser cone biopsies were performed, whereas 797 LLETZ biopsies were recorded,
      during the study period. There was no difference in the mean age in the two
      groups. However, there is a proportional increase in the volume of the cone as
      the height of the cone increases, and a significant number of the values are
      skewed, suggesting that the diameter of the base of the cone contributes
      significantly to the total volume. Laser cone biopsies (median volume 1.84 cm(3),
      95% CI 1.98-2.54 cm(3)) account for a larger volume of tissue excised compared
      with LLETZ (median volume 0.78 cm(3), 95% CI 0.91-1.02 cm(3)) (P < 0.0001). This
      relationship is not altered when the two procedures are stratified for grade of
      lesion, i.e. excision for low-grade cervical intraepithelial neoplasia (CIN)
      (laser median volume 1.55 cm(3), 95% CI 1.46-2.06; LLETZ median volume 0.62
      cm(3), 95% CI 0.73-0.88 cm(3)) (P < 0.0001) or high-grade CIN (laser median
      volume 1.84 cm(3), 95% CI 2.11-2.53 cm(3); LLETZ median volume 0.82 cm(3), 95% CI
      0.94-1.07 cm(3)) (P < 0.0001). CONCLUSIONS: The volume of cervical tissue removed
      during laser conisation is significantly more than that removed with LLETZ. The
      indication of the cone biopsy does influence the volume of tissue removed.

PMID- 20156212
TI  - Variation in the incidence of and risk factors for the development of
      nephrolithiasis after radical or partial nephrectomy.
AB  - OBJECTIVE: to examine incidence of and risk factors for the development of
      nephrolithiasis in patients treated with radical nephrectomy (RN) or partial
      nephrectomy (nephron-sparing surgery, NSS). PATIENTS AND METHODS: the study
      comprised a single-centre review of 749 patients treated with RN or NSS from
      August 1987 to June 2006. Demographics, medical and stone history, metabolic
      variables and postoperative stone events were recorded. Data were analysed within
      subgroups based on treatment (RN vs NSS). Multivariate analysis was used to
      identify risk factors for postoperative stone formation. RESULTS: in all, 499
      patients had RN and 250 had NSS (mean age 57.9 years; mean follow-up 6.3 years).
      There were no significant differences in their demographic factors, but tumours
      were significantly larger in RN (P < 0.001). There was no significant difference
      in preoperative urinary pH < 6.0 or stone history. Significantly fewer patients
      after NSS than RN formed calculi (NSS 1.6% vs RN 8.4%, P < 0.001), developed
      hypobicarbonataemia (NSS 7.2% vs RN 12.8%, P= 0.020), and a urinary pH of <6.0
      (NSS 11.2% vs RN 19.4%, P= 0.004). Multivariate analysis showed that RN (odds
      ratio 18.18), postoperative urinary pH < 6 (15.63), previous stone disease
      (13.7), age <60 years (7.33, all P < 0.001), body mass index >= 30 kg/m(2) (3.26,
      P= 0.033), male gender (2.67, P= 0.039), and hypobicarbonataemia (2.46, P= 0.034)
      were significantly associated with the development of postoperative calculi.
      CONCLUSIONS: patients undergoing RN have a significantly higher incidence of
      postoperative nephrolithiasis than a well-matched cohort undergoing NSS. In
      addition to RN, male sex, urinary pH < 6.0, hypobicarbonataemia, history of stone
      disease, obesity, and age <60 years were significantly associated with
      postoperative stone formation.

PMID- 20156213
TI  - Patterns of psychiatric and physical comorbidities associated with panic disorder
      in a nationwide population-based study in Taiwan.
AB  - OBJECTIVE: This study aims to document a range of risk of psychiatric and
      physical comorbidities among PD patients using a nationwide population-based
      dataset in Taiwan. METHOD: A total of 3672 patients with at least three consensus
      diagnoses with PD were included, together with 18 360 matched controls without
      PD. Logistic regression analyses were performed after adjusting for
      sociodemographic characteristics. RESULTS: After adjusting for the patients' sex,
      age and geographic region, patients with PD were more likely to have major
      depressive disorder (OR = 23.45), bipolar disorder (OR = 15.54), cardiac
      dysrhythmia (OR = 15.12), coronary heart disease (OR = 7.69), myocardial
      infarction (OR = 6.55), irritable bowel syndrome (OR = 4.82), peptic ulcers (OR =
      4.30), cerebrovascular disease (OR = 3.61), hypertension (OR = 3.31), epilepsy
      (OR = 3.07), hepatitis (OR = 2.70), hyperlipidemia (OR = 2.20), asthma (OR =
      2.17), schizophrenia (OR = 2.14), neoplasms (OR = 2.02), renal disease (OR =
      1.89) and diabetes (OR = 1.26), compared to patients in the comparison cohort.
      CONCLUSION: We conclude that PD is associated with an array of psychiatric and
      physical illnesses.

PMID- 20156214
TI  - Toll-like receptor 9 expression in breast and ovarian cancer is associated with
      poorly differentiated tumors.
AB  - Toll-like receptor 9 (TLR9) activates the innate immune response when exposed to
      non-methylated CpG-DNA. TLR9 was recently shown to be expressed by cancer cells
      which have been previously characterized by global hypomethylation. We set out to
      examine the expression and molecular activity of TLR9 in breast and ovarian
      cancer cells. Firstly, we confirmed higher levels of hypomethylated DNA in the
      serum of patients with metastatic breast cancer (n = 18) versus age-matched tumor
      free women (n = 18). In breast cancer cell lines and tissues, TLR9 mRNA
      expression was associated with estrogen-receptor (ER) status (n = 124, P =
      0.005). Expression also correlated with increasing tumor grade in both breast (P
      = 0.03) and ovarian cancer specimens (n = 138, P = 0.04). Immunohistochemical
      analysis of formalin-fixed paraffin-embedded (FFPE) breast cancer tissues
      revealed higher TLR9 protein expression in hormone-receptor (HR)-negative
      specimens (n = 116, P < 0.001). Using an in vitro scratch assay, we observed that
      cell lines transfected to overexpress TLR9 demonstrated increased cellular
      migration when stimulated with CpG-DNA. When assessing the molecular activity of
      TLR9 in breast cancer, we found a strong positive correlation of nuclear factor
      kappa B (NF-kappaB) activity with TLR9 mRNA expression (correlation coefficient r
      = 0.7, P < 0.001). Finally, immunofluorescence analysis of BT-20 and Hs578T
      breast cancer cell lines showed partial colocalizations of CpG-DNA with TLR9,
      which diminished when the cells were exposed to methylated CpG-DNA (mCpG-DNA) or
      control GpC-DNA. In summary we demonstrate that TLR9 expression is associated
      with poor differentiation in breast and ovarian cancer specimens, and that TLR9
      overexpression and stimulation with hypomethylated DNA augments the migratory
      capacity of cancer cell lines.

PMID- 20156215
TI  - Performance of the galactomannan antigen detection test in the diagnosis of
      invasive aspergillosis in children with cancer or undergoing haemopoietic stem
      cell transplantation.
AB  - Serum galactomannan (GM) antigen detection is not recommended for defining
      invasive aspergillosis (IA) in children undergoing aggressive chemotherapy or
      allogeneic haemopoietic stem cell transplantation (HSCT). The ability of the GM
      test to identify IA in children was retrospectively evaluated in a cohort of
      children. Test performance was evaluated on samples that were collected during
      195 periods at risk of IA. Proven IA was diagnosed in seven periods, all with
      positive GM test results (true positives, 4%), and possible IA was diagnosed in
      15 periods, all with negative GM test results (false negatives, 8%). The test
      result was positive with negative microbiological, histological and clinical
      features in three periods (false positives, 1%), and in 170 periods it was
      negative with negative microbiological, histological and clinical features (true
      negatives, 87%). The sensitivity was 0.32 and the specificity was 0.98; the
      positive predictive value was 0.70 and the negative predictive value was 0.92.
      The efficiency of the test was 0.91, the positive likelihood ratio was 18.3, and
      the negative likelihood ratio was 1.4. The probability of missing an IA because
      of a negative test result was 0.03. Test performance proved to be better during
      at-risk periods following chemotherapy than in periods following allogeneic HSCT.
      The GM assay is useful for identifying periods of IA in children undergoing
      aggressive chemotherapy or allogeneic HSCT.

PMID- 20156216
TI  - Culture of per-wound bone specimens: a simplified approach for the medical
      management of diabetic foot osteomyelitis.
AB  - Surgical percutaneous bone biopsy specimen after a 14-day antibiotic-free period
      represents the gold standard of care for diabetic foot osteomyelitis but may be
      difficult to implement in many institutions. We evaluate a simplified strategy
      based on the results of per-wound bone specimen culture. For that purpose, we
      retrospectively reviewed the charts of 80 consecutive patients with diabetic
      osteomyelitis and bone sample obtained via the wound after a careful debridement.
      The outcome was defined as favourable if there was a complete healing of the
      wound with no sign of infection and stable or improved bone X-ray 6 months after
      antibiotic therapy completion. Culture of bone specimens was positive in 96% of
      patients, although half of the patients did receive a course of antimicrobials
      within 14 days of the bone specimen being obtained. A total of 129 bacterial
      isolates were obtained from bone cultures with a mean of 1.6 +/- 1 isolates per
      patient (Staphylococcus aureus: 33%; central nervous system: 14%; streptococci:
      9%; enterococci: 12%; corynebacteria: 4%; Gram-negative bacilli: 20%; anaerobes:
      4%). Forty-six percent of cultures were monomicrobial. The mean duration of
      follow-up from diagnosis was 17 +/- 1 months. Six months after discontinuation of
      antibiotic, six patients (7.5%) had died, nine were considered as therapeutic
      failures and 65 were considered as cured. Fifty-four of these 65 patients had
      follow-up data available at 1 year and remained in remission. In conclusion, a
      simplified procedure based on the culture of bone sample obtained via the ulcer
      after a careful debridement of the wound is effective in the medical management
      of diabetic foot osteomyelitis.

PMID- 20156217
TI  - Eleven-year retrospective survey of candidaemia in a university hospital in
      southwestern Greece.
AB  - The aim of this study was to investigate the isolation and distribution rate of
      Candida spp. in blood cultures and evaluate antifungal susceptibility during an
      11-year period (1998-2008) at a tertiary-care hospital. The causative species
      were as follows: Candida albicans, 163 strains (64%); Candida parapsilosis, 35
      strains (13.7%); Candida glabrata, 25 strains (9.8%); Candida tropicalis, 19
      strains (7.4%); and other Candida spp., 13 strains (5.1%). Candidaemia is
      predominantly caused by C. albicans. C. parapsilosis is the most common non
      albicans Candida isolated in neonatal intensive-care units. All Candida isolates
      remain susceptible to amphotericin B, whereas the highest degree of resistance
      was observed for azoles.

PMID- 20156218
TI  - Usefulness of two new methods for diagnosing metapneumovirus infections in
      children.
AB  - Human metapneumovirus (hMPV) is associated with acute respiratory tract
      infections, mainly in paediatric patients. The aim of this study was to evaluate
      the usefulness of two new commercial techniques available for the detection of
      hMPV in clinical samples from children: an enzyme immunoassay, hMPV EIA (Biotrin
      International Ltd), and a molecular assay, real-time RT-PCR (Pro hMPV Real Time
      Assay Kit; Prodesse). A total of 184 nasopharyngeal aspirate specimens from 173
      children aged less than 5 years who were hospitalized with acute wheezing were
      analysed. Respiratory syncytial virus was detected in 27% of the samples,
      followed by influenza A virus (6%), parainfluenza virus (PIV)3 (2.2%), adenovirus
      (2%), PIV1 (1.1%), PIV2 (1.1%), and influenza B virus (0.5%). The presence of
      hMPV was tested in all samples, using the real-time RT-PCR and EIA. Real-time RT
      PCR detected 13 hMPV-positive samples (8%), and EIA detected 17 (9.3%). When the
      EIA results were compared with those of real-time RT-PCR for the detection of
      hMPV, a good correlation was found (94%). A relatively low co-infection rate
      (15%) was observed in our patients. RT-PCR and EIA provide robust methods for the
      diagnosis of hMPV infection in children.

PMID- 20156219
TI  - Detection of human metapneumovirus and respiratory syncytial virus by duplex real
      time RT-PCR assay in comparison with direct fluorescent assay.
AB  - Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are
      important respiratory pathogens of small children and adults. The present study
      aimed to design a sensitive real-time RT-PCR assay for the detection of hRSV and
      hMPV in comparison with direct fluorescent assay (DFA) and to determine the
      incidence of hMPV and hRSV as causative agents of respiratory infections in a
      Finnish population. For DFA detection of hMPV antigen, four commercial antibodies
      were evaluated. The duplex real-time RT-PCR assay achieved a sensitivity of 10(3)
      copies/mL of specimen for hRSV and hMPV type A viruses and 10(4) copies/mL for
      type B hMPV. The detection rate of the RT-PCR assay was compared with those for
      DFA detection of hMPV and hRSV in analyses of 350 nasopharyngeal aspirates sent
      to HUSLAB, Helsinki University Hospital, for routine virus diagnostics during
      November 2007 to June 2008. Of the samples analyzed, 43 (12.3%) were positive for
      hRSV by DFA and an additional 13 specimens (3.7%) were positive for hRSV by RT
      PCR. Only four samples (1.1 %) were found to be positive for hMPV RNA by RT-PCR,
      with two of them also positive by DFA. The duplex real-time RT-PCR assay
      described in the present study can therefore be applied for efficient
      identification of hMPV and hRSV in clinical specimens and collection of
      information on the epidemiology and clinical outcome of these viruses.

PMID- 20156220
TI  - Regional differences in deceased donor liver transplantation and their
      implications for organ utilization and allocation.
AB  - We examined the UNOS database from 7/15/00-7/17/05 for Regional deceased donor
      liver utilization. For each region, we performed logistic regression and derived
      odds ratios (OR) for donor characteristics associated with livers being
      transplanted outside of the region or not transplanted at all. Regions with
      smallest and least significant OR were considered aggressive users of suboptimal
      organs. We estimated how many untransplanted livers from less aggressive regions
      might be used by more aggressive regions. Only Region 9 was significantly more
      aggressive than others (median OR: 6 vs. 16; p < 0.01; median OR size: 1.4 vs.
      3.6; p < 0.01). Region 9 transplanted at higher median Model for End-stage Liver
      Disease (MELD) score (20.4 [6-73] vs. 18.3 [6-70], p < 0.01), but had the lowest
      one- and five-yr graft survival (p < 0.01). Of 30,474 livers, 5056 were not
      transplanted, of which 3690 were procured outside Region 9 but met Region 9 use
      criteria. Of these, 1488 and 1807 livers had donor risk indices <= 2, for
      hypothetical 12 and 8 h cold ischemia time (CIT), respectively. Regional
      differences in liver utilization are profound. Region 9 is significantly more
      aggressive. At the most, 297-361 organs per year may have been used under Region
      9's use criteria but overall graft survival may have declined.

PMID- 20156221
TI  - Cost-effectiveness of screening for recurrent hepatocellular carcinoma after
      liver transplantation.
AB  - The effectiveness of screening and treatment of recurrent hepatocellular
      carcinoma (HCC) after liver transplantation (LT) remains undefined. Our aim was
      to evaluate the potential cost-effectiveness of screening for recurrent HCC after
      LT. We constructed a Markov model of the natural history after LT for HCC. We
      superimposed screening with computed tomography, alpha-fetoprotein, and chest X
      ray every six months for 1-5 yr after LT, with resection for treatable
      recurrence. Screening only those whose explant pathology exceeded Milan Criteria
      (MC) for two yr cost $ 138,000/life-yr gained, and the incremental cost of
      screening all patients was $ 340,000/life-yr gained. Screening for longer than
      two yr incurred progressively higher incremental costs/life-yr gained. The most
      critical variable in sensitivity analyses was the survival benefit of finding a
      resectable recurrence. With the most favorable assumptions for a two-yr screening
      duration, screening those whose explant pathology exceeded MC cost $ 91,000/life
      yr gained. In conclusion, screening for HCC recurrence after LT would probably
      yield most of its benefit in the first two yr, but at a relatively high cost/life
      yr gained. Screening for two yr in only those whose explant pathology exceeds MC
      may be relatively cost-effective depending on the survival benefit of resection.

PMID- 20156222
TI  - Low prevalence of HBV DNA in the liver allograft from anti-HBc-positive donors: a
      single-center experience.
AB  - Allografts from donors positive for antibody to hepatitis B core antigen (anti
      HBc(+)) can transmit hepatitis B virus (HBV) to the recipients. We aimed to study
      the prevalence of HBV DNA in liver allografts from anti-HBc(+) donors. Between
      January 2003 and December 2008, this retrospective study identified 18 patients
      who received a liver from an anti-HBc(+) donor. Pre- and post-transplantation HBV
      serology and serum HBV DNA level of the study subjects were reviewed. DNA
      extracted from liver biopsy tissue was used for PCR assay. Immunohistochemistry
      was also performed to determine viral protein expression. We observed a low
      prevalence of HBV DNA in allografts from anti-HBc(+) donors even among patients
      who did not receive prophylaxis. Only one of 18 patients had detectable HBV DNA
      in the liver allograft. This recipient was seronegative for HBV before
      transplantation and did not receive prophylaxis after transplantation, and
      developed de novo hepatitis B. Of the five patients who were positive for both
      antibody to hepatitis B surface antigen and anti-HBc before transplantation and
      did not receive prophylaxis after transplantation, none developed HBV infection.
      Prophylaxis for HBV is important for seronegative recipients receiving a liver
      from an anti-HBc(+) donor. Such prophylaxis may not be necessary for recipients
      who do not have detectable HBV DNA in the liver allograft.

PMID- 20156223
TI  - Patent foramen ovale does not have a negative impact on early outcomes in
      patients undergoing liver transplantation.
AB  - OBJECTIVE: To identify the impact of the presence of patent foramen ovale (PFO)
      in patients undergoing liver transplantation. METHODS: Twenty-seven pre-liver
      transplant patients who had a PFO (PFO group) were identified and compared with
      61 patients without PFO (NoPFO group). Patients were matched according to age,
      gender and cause of liver disease. The diagnosis of PFO was made by transthoracic
      echocardiography prior to liver transplantation. Patient baseline characteristics
      and complications during the early post-transplant period were analyzed. RESULTS:
      The mean age in the PFO group was 47 +/- 14 (range 18-68) yr and 50 +/- 11 (range
      12-65) yr in the NoPFO group. The PFO group had a mean model for end-stage liver
      disease (MELD) score of 15 +/- 10 whereas in the NoPFO group the MELD score was
      19 +/- 10 (p = 0.08). There were non-significant differences in echocardiographic
      parameters between groups. Duration of mechanical ventilation and the incidence
      of neurological complications were similar. Thirty-day mortality rate was similar
      in both groups; only one patient in the NoPFO group died within the first 30 days
      post-transplantation. CONCLUSIONS: The presence of PFO in patients with end-stage
      liver disease undergoing liver transplantation does not appear to affect patient
      outcomes during the peri-operative period.

PMID- 20156224
TI  - Synchronous hepatic, mesenteric and pulmonary Epstein-Barr virus-associated
      smooth muscle tumors in a renal transplant recipient.
AB  - Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) are distinct lesions
      that occur in immunocompromised patients. EBV-SMT following solid organ
      transplantation are rare and generally have an indolent biological behavior. Post
      transplant EBV-SMT have been reported in various anatomical locations. This
      report describes a synchronous and multicentric development of EBV-SMT in liver,
      mesentery, and lung of a 33-yr-old male patient, 10 yr after a deceased allograft
      renal transplantation. The hepatic and mesenteric tumors were available for
      study. These tumors were composed of bland looking, desmin-positive, spindle
      shaped cells which showed a strong nuclear staining for EBV with in situ
      hybridization technique. A literature review of post solid organ transplant EBV
      SMT in the liver and lung, particularly regarding their pathogenesis,
      synchronicity and biological behavior would be provided.

PMID- 20156225
TI  - Longitudinal changes in tooth/single-implant relationship and bone topography: an
      8-year retrospective analysis.
AB  - PURPOSE: To evaluate longitudinal changes in tooth/implant relationship and bone
      topography at single implants with a microthreaded, conical marginal portion
      (Astra Tech ST(r) implants, Astra Tech AB, Molndal, Sweden). MATERIAL AND
      METHODS: Thirty-one subjects with single implant-supported restorations in the
      esthetic zone were included. Radiographs obtained at crown installation and 1, 5,
      and 8 years of follow-up were analyzed with regard to changes in (1) bone level
      at the implant and adjacent teeth and (2) vertical position of adjacent teeth
      relative to the single implant. RESULTS: The mean marginal bone loss amounted to
      0.1 mm at both implants and adjacent teeth during the 8 years of follow-up.
      Regression analysis failed to identify significant explanatory factors for
      observed variance in bone level change at the adjacent tooth surfaces. Vertical
      change in position of the teeth relative to the implants was more frequent and
      significantly greater in incisor compared with premolar tooth region but not
      associated with gender or age. CONCLUSIONS: The marginal bone level at teeth
      adjacent to single implants with a microthreaded conical marginal part was not
      influenced by horizontal and vertical tooth-implant distances. Continuous
      eruption of adjacent teeth may result in infraocclusal positioning of a single
      implant restoration.

PMID- 20156226
TI  - Bone response to free-form fabricated hydroxyapatite and zirconia scaffolds: a
      transmission electron microscopy study in the human maxilla.
AB  - BACKGROUND: Understanding the interfacial reactions to synthetic bone
      regenerative scaffolds in vivo is fundamental for improving osseointegration and
      osteogenesis. Using transmission electron microscopy, it is possible to study the
      biological response of hydroxyapatite (HA) and zirconia (ZrO(2) ) scaffolds at
      the nanometer scale. PURPOSE: In this study, the bone-bonding abilities of HA and
      ZrO(2) scaffolds produced by free-form fabrication were evaluated in the human
      maxilla at 3 months and 7 months. MATERIALS AND METHODS: HA and ZrO(2) scaffolds
      (o: 3 mm) were implanted in the human maxilla, removed with surrounding bone,
      embedded in resin, and sectioned. A novel focused ion beam (FIB) sample
      preparation technique enabled the production of thin lamellae for study by
      scanning transmission electron microscopy. RESULTS: Interface regions were
      investigated using high-angle annular dark-field imaging and energy-dispersive X
      ray spectroscopy analysis. Interfacial apatite layers of 80 nm and 50 nm
      thickness were noted in the 3- and 7-month HA samples, respectively, and bone
      growth was discovered in micropores up to 10 um into the samples. CONCLUSIONS:
      The absence of an interfacial layer in the ZrO(2) samples suggest the formation
      of a direct contact with bone, while HA, which bonds through an apatite layer,
      shows indications of resorption with increasing implantation time. This study
      demonstrates the potential of HA and ZrO(2) scaffolds for use as bone
      regenerative materials.

PMID- 20156227
TI  - Deformation of stereolithographically produced surgical guides: an observational
      case series report.
AB  - BACKGROUND: Template-based computer-guided implant placement holds the promise of
      more precise and less traumatic placement of dental implants. Errors in the
      fabrication process of the surgical guide may lead to unfavorable clinical
      outcomes. PURPOSE: This report discusses the potential of unintentional
      volumetric deformation of stereolithographically (SLA) produced surgical guides
      (NobelGuide, Nobel Biocare AB, Goteborg, Sweden) compared with the original scan
      denture. MATERIALS AND METHODS: Three-dimensional radiographic data acquired by
      medical computerized tomography (CT) or cone beam CT (Newtom 3G, AFP Imaging
      Corporation, Elmsford, NY, USA) can be utilized in specialized software to
      develop treatment planning for dental implant placement. This information can
      then be transferred to the patient via a surgical guide. Stereolithography is a
      rapid prototyping process that can be used to create such a guide stent. Three
      cases are shown describing different levels of deformation of SLA-produced
      surgical guides. RESULTS: Unintentional deformation of SLA-produced surgical
      guides is possible. Deformation of surgical guides can create dissimilarity
      between the virtually planned position and the actual position of the implants.
      CONCLUSION: Incorrect setting of the ISO values for the segmentation of the scan
      denture has been found to be a factor in the deformation of SLA-produced surgical
      guides, although more, at this time known but also less understood, issues appear
      to be involved. Only one manufacturer's product is discussed; further research is
      warranted to determine if the discrepancies are process or product based. It
      might be prudent to closely evaluate the volumetric congruence of SLA-produced
      surgical stents before their clinical use to prevent undesired clinical outcomes.

PMID- 20156228
TI  - Successful treatment of early implant failure: a case series.
AB  - BACKGROUND: The aim of this longitudinal study was to evaluate the effect of
      combined treatment on early progressive bone loss around dental implants.
      METHODS: The study sample consisted of 18 implants presenting at 4-6 weeks
      postplacement with early progressive bone loss. Clinical examination indicated
      the presence of a fistula in the soft tissue covering the implants in most cases.
      Defects around the implants were curetted, exposed implant surfaces were
      mechanically debrided and treated with tetracycline solution, and the defects
      were filled with bone graft and doxycycline powder. Bioabsorbable membranes were
      used. Final crowns were placed after 6 months. The patients were followed for an
      average of 30 months. RESULTS: The surgical sites healed without complication. At
      the time of loading, the defects were completely restored. At 12 months
      postloading, there was crestal bone loss to the level of the first thread
      (average, 1.3 mm). Pocket depths ranged from 3 to 5 mm (average, 3.6 mm) with no
      bleeding. No further changes were noticed throughout the remaining follow-up
      visits. All implants were successful according to the criteria proposed by
      Albrektsson and colleagues. CONCLUSIONS: Early detection and treatment of early
      progressive bone loss around dental implants are the key to saving early failing
      implants. The author recommends reevaluation visits 4-6 weeks postimplant
      placement to detect any signs of early failure so that immediate treatment can be
      undertaken if needed.

PMID- 20156229
TI  - The influence of PRP on early bone formation in membrane protected defects. A
      histological and histomorphometric study in the rabbit calvaria.
AB  - BACKGROUND: Platelet rich plasma (PRP) has been proposed to be a useful adjunct
      to bone grafting. PURPOSE: The aim of the present study was to assess new bone
      formation in bone regeneration procedures using platelet rich plasma (PRP) alone
      or in combination with autogenous bone. MATERIALS AND METHODS: Four surgically
      created, monocortical defects 5 mm in diameter in the calvariae of 15 New Zealand
      rabbits were grafted with a coagulum-filled control, PRP, particulated autogenous
      bone alone (A), or combined with PRP (A-PRP). RESULTS: Mean platelet
      concentration of 1,761,930 +/- 680,200/ul was achieved (5.30 +/- 2.63 * fold of
      baseline). Animals were sacrificed 1, 2, and 4 weeks later. Histomorphometric
      analysis showed no statistical difference for total new bone formation at any
      time point, however, a detailed analysis revealed a statistically significant
      higher percentage of lamellar bone than woven bone for the autogenous bone group
      at 2 weeks; all other groups demonstrated equal percentages of either bone type.
      At 4 weeks, all groups revealed a statistically greater component of lamellar
      bone over woven bone. Graft resorption rate was similar for both A and A-PRP. PRP
      platelet concentration was significantly positively correlated with TGF-beta1 but
      not with PDGF-AB. CONCLUSIONS: Within the limits of the chosen animal model, this
      study demonstrated that PRP during early healing, whether alone or mixed with
      autogenous bone, did not lead to greater bone remodelling, as compared to
      coagulum. In contrast, autogenous bone alone demonstrated accelerated bone
      remodelling at 2 weeks.

PMID- 20156230
TI  - Immediate rehabilitation of the extremely atrophic mandible with fixed full
      prosthesis supported by four implants.
AB  - PURPOSE: To prospectively assess the outcome of immediate rehabilitation of
      extremely atrophic mandibles by a full-arch fixed bridge anchored to four
      implants. MATERIAL AND METHODS: Twenty patients with edentulous mandibles were
      included in the study. Each patient received a full-arch fixed bridge supported
      by two axial and two distal tilted implants. Prosthetic loading was applied
      within 48 hours of surgery. Patients were scheduled for follow-up every 6 months
      up to 2 years and annually until 5 years. Radiographic evaluation of marginal
      bone level change was performed at 1 year. RESULTS: All patients were followed
      for a minimum of 1 year (range 20-48 months, mean 30.1 months). No failures were
      recorded to date. The 1-year implant survival rate and prosthesis success rate
      were 100%. Marginal bone loss around axial and tilted implants was similar at 12
      month evaluation, being, respectively, 0.6 +/- 0.3 (standard deviation) mm and
      0.7 +/- 0.4 mm. High patient's level of satisfaction was recorded for function,
      phonetics, and aesthetics. CONCLUSION: This technique could be considered a
      viable treatment option for the rehabilitation of the atrophic mandible.

PMID- 20156231
TI  - Ten-year retrospective follow-up study of the TiOblast dental implant.
AB  - PURPOSE: Long-term results in the clinical outcome of different implant systems,
      including high patient numbers and a long follow-up time, are rare. This
      retrospective study evaluated the cumulative survival rate of a self-tapping,
      cylindrical implant system with a conical implant-abutment connection after 10
      years of prosthetic loading. MATERIALS AND METHODS: A total of 516 TiOblast
      implants (Astra Tech AB, Molndal, Sweden) were placed in 108 patients. The
      patients were treated in the Department of Oral and Maxillofacial Surgery,
      Johannes Gutenberg University, Mainz, Germany, between September 1994 and May
      2005. The main indications for implantation were the treatment of edentulous
      mandibles (74%) and partial edentulism (15%). Twenty-three implants were placed
      postradiation, and a further 64 implants were irradiated after insertion. In 153
      implants, a bony augmentation was conducted prior to implantation. RESULTS: The
      in situ rate was 89.7% after an average implantation time of 108 months. Eighty
      three patients with 403 implants were available for investigation. Seventeen
      patients with 76 implants have died since 1994. Absence of osseointegration (n =
      22), peri-implantitis (n = 18), fracture of the implants (n = 9), failing of
      primary stability (n = 2), and implants next to tumors (n = 2) were the reasons
      of explantation in 26 patients. Under analysis with different implant success
      assessment criteria, the success rate showed results from 76 to 89%. CONCLUSION:
      With respect to the critical patient selection including a high number of
      patients with minor and major augmentations, the 10-year clinical use of the
      studied implant system showed acceptable results.

PMID- 20156232
TI  - The effect of surface processing of titanium implants on the behavior of human
      osteoblast-like Saos-2 cells.
AB  - BACKGROUND: The surface qualities of dental implants appear to modulate
      osteoblasts' growth and differentiation, affecting bone healing. During
      manufacturing of implants, the surface quality is affected by industrial
      processes. PURPOSE: To examine the effect of manufacturing procedures on the
      growth and differentiation of human osteoblast-like cells, Saos-2. MATERIALS AND
      METHODS: Saos-2 cells were cultured on titanium (Ti) disks. Cell growth was
      examined using the XTT assay, and cell differentiation was tested by alkaline
      phosphatase (ALP) activity and osteocalcin secretion. The following variables
      were examined: roughening of the surface by sandblasting and acid-etching, aging
      of the acid used for etching, fluoride modification of the surface, and the type
      of the packaging material. RESULTS: An inverse relationship was noted between
      Saos-2 growth and ALP activity on the tested surfaces. Roughening of the surface
      tended to decrease cell proliferation and to increase differentiation. Immersion
      of up to 200 cycles in acid decreased proliferation and increased
      differentiation. Cells grown on fluoride-modified surfaces exhibited more ALP
      activity as compared to the unmodified surfaces. No difference was noted between
      the three packaging materials tested. CONCLUSIONS: The data suggests that
      industrial processes may affect the behavior of osteoblast-like cells around
      titanium implants and should be monitored carefully by bioassays.

PMID- 20156233
TI  - Urban Mexican-American mothers' beliefs about caries etiology in children.
AB  - OBJECTIVES: Caries is a severe condition which disproportionately affects Latino
      children in the US. This study sought contextual understanding of urban, low
      income Mexican-American mothers' beliefs, perceptions, knowledge and behavior
      surrounding causes of caries. METHODS: In urban San Jose, CA, a qualitative study
      was conducted with a convenience sample of Mexican-American mothers of young
      children about their beliefs and knowledge about the causes of caries. Audio
      taped in-depth interviews with open-ended questions, primarily in Spanish, were
      translated to English and then transcribed verbatim. Texts were independently
      read and thematically analyzed by two researchers. RESULTS: Even while expressing
      uncertainty, all 48 mothers mentioned specific causes of caries, most frequently
      citing candy or juice consumption (85%), poor oral hygiene (65%) and use of the
      bottle (52%). Mothers rarely recognized cariogenic foods beyond candy, did not
      know or perform recommended oral hygiene routines, and demonstrated confusion and
      uncertainty about exactly how baby bottles are detrimental to teeth. Nearly half
      of these mothers also mentioned secondary cavity causes, such as genetics, lack
      of calcium, not going to the dentist or lack of fluoride. Mothers did not mention
      the role of bacteria. While mothers recognized that oral hygiene can counteract
      the detrimental effects of candy consumption, they did not recognize its
      beneficial effects in other contexts. Nor did they know about other preventive
      activities. CONCLUSIONS: Mothers recognized the three major important factors
      causing caries: sugar consumption, poor oral hygiene and bottle use. However,
      their knowledge is limited in depth and specificity which restricts development
      of caries prevention behaviors. More comprehensive education is needed, including
      about caries prevention (oral hygiene) behaviors, which could lead to an
      increased sense of self-efficacy with respect to their children's oral health.

PMID- 20156234
TI  - The association between fluoride in drinking water and dental caries in Danish
      children. Linking data from health registers, environmental registers and
      administrative registers.
AB  - OBJECTIVES: To study the association between fluoride concentration in drinking
      water and dental caries in Danish children. METHODS: The study linked registry
      data on fluoride concentration in drinking water over a 10-year period with data
      on dental caries from the Danish National Board of Health database on child
      dental health for 5-year-old children born in 1989 and 1999, and for 15-year-old
      children born in 1979 and 1989. The number of children included in the cohorts
      varied between 41.000 and 48.000. Logistic regression was used to assess the
      correlations, adjusting for gender and taxable family income as a proxy variable
      for socioeconomic status. RESULTS:   Fluoride concentration in drinking water
      varied considerably within the country from very low (<0.10 mg/l) to more than
      1.5 mg/l. Only little variation was found over the 10-year study period. Dental
      caries in both 5-year-olds and 15-year-olds decreased over the study period. An
      inverse relation between the risk of dental caries and fluoride concentration in
      drinking water was found in both primary and permanent teeth. The risk was
      reduced by approximately 20% already at the lowest level of fluoride exposure
      (0.125-0.25mg/l). At the highest level of fluoride exposure (>1 mg/l), a
      reduction of approximately 50% was found. Similar findings were found if analysis
      was limited to children residing in the same place during the entire study
      period. CONCLUSIONS: The study confirmed previous findings of an inverse relation
      between fluoride concentration in the drinking water and dental caries in
      children. This correlation was found in spite of the extensive use of fluoridated
      toothpaste and caries-preventive programs implemented by the municipal dental
      services in Denmark. Linking Danish health registers with environmental and
      administrative registers offers an opportunity for obtaining sample sizes large
      enough to identify health effect, which otherwise could not be identified.

PMID- 20156235
TI  - Factor structure of a conceptual model of oral health tested among 65-year olds
      in Norway and Sweden.
AB  - BACKGROUND: No studies have tested oral health-related quality of life models in
      dentate older adults across different populations. OBJECTIVES: To test the factor
      structure of oral health outcomes within Gilbert's conceptual model among 65-year
      olds in Sweden and Norway. It was hypothesized that responses to 14 observed
      indicators could be explained by three correlated factors, symptom status,
      functional limitations and oral disadvantages, that each observed oral health
      indicator would associate more strongly with the factor it is supposed to measure
      than with competing factors and that the proposed 3-factor structure would
      possess satisfactory cross-national stability with 65-year olds in Norway and
      Sweden. METHODS: In 2007, 6078 Swedish- and 4062 Norwegian adults borne in 1942
      completed mailed questionnaires including oral symptoms, functional limitations
      and the eight item Oral Impacts on Daily Performances inventory. RESULTS: Model
      generation analysis was restricted to the Norwegian study group and the model
      achieved was tested without modifications in Swedish 65-year olds. A modified 3
      factor solution with cross-loadings, improved the fit to the data compared with a
      2-factor- and the initially proposed 3-factor model among the Norwegian
      [comparative fit index (CFI) = 0.97] and Swedish (CFI = 0.98) participants. All
      factor loadings for the modified 3-factor model were in the expected direction
      and were statistically significant at CR > 1. Multiple group confirmatory factor
      analyses, with Norwegian and Swedish data simultaneously revealed acceptable fit
      for the unconstrained model (CFI = 0.97), whereas unconstrained and constrained
      models were statistically significant different in nested model comparison.
      CONCLUSIONS: Within construct validity of Gilbert's model was supported with
      Norwegian and Swedish 65-year olds, indicating that the 14-item questionnaire
      reflected three constructs; symptom status, functional limitation and oral
      disadvantage. Measurement invariance was confirmed at the level of factor
      structure, suggesting that the 3-factor model is comparable to some extent across
      65-year olds in Norway and Sweden.

PMID- 20156236
TI  - Familial nuchal cystic hygroma without fetal effects: Genetic counselling and
      further evidence for an autosomal recessive subtype.

PMID- 20156237
TI  - Effect of recombinant human fibroblast growth factor-2 on bone formation in
      rabbit mandibular distraction models using beta-tricalcium phosphate.
AB  - This study was designed to evaluate the effect of recombinant human fibroblast
      growth factor-2 (rhFGF-2) on the amount and period of new bone formation in
      rabbit mandibular distraction models using beta-tricalcium phosphate (beta-TCP)
      as a bone graft substitute. Sixteen male Japanese White rabbits were divided into
      the following four experimental groups: 1, distraction alone; 2, distraction with
      beta-TCP granules; 3, distraction with rhFGF-2 (25 microg/50 microL) injected
      into beta-TCP granules; and 4, distraction with rhFGF-2 (100 microg/50 microL)
      injected into beta-TCP granules. The bones were harvested at 4 weeks after the
      operation and examined using soft radiography, micro-computed tomography (micro
      CT), and peripheral quantitative computed tomography (pQCT). The dissected
      mandibles were stained using the Villanueva bone staining method, and the amount
      of new bone formed, bioresorption of beta-TCP, and new blood vessel formation
      were morphometrically calculated using bone histomorphometry. Radiopaque areas
      were observed more frequently in the distracted area of groups 3 and 4. Micro-CT
      analysis revealed partial new bone formation in the central region of the
      distracted area in groups 3 and 4. pQCT analysis revealed increased bone mineral
      density in groups 3 and 4. Histomorphometric analysis revealed increased newly
      formed bone and blood vessel areas in groups 3 and 4. In group 4, the number of
      osteoclasts around the beta-TCP granules had significantly increased. The present
      findings suggested that the combined use of rhFGF-2 and beta-TCP reduced the
      treatment period for distraction osteogenesis and accelerated the formation of a
      new high-quality bone.

PMID- 20156238
TI  - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin suggests abnormal palate
      development after palatal fusion.
AB  - Mouse embryos exposed to 2,3,7,8-tetrachloridedibenzo-p-dioxin (TCDD) develop
      cleft palates and hydronephrosis. Cleft palates occur after TCDD exposure due to
      contact and/or fusion failure. We investigated whether cleft palate can be
      induced by dissociation of the palatine process after fusion. Pregnant mice on
      gestational day (GD) 12 were randomly divided into two groups: one group was
      administered through gastric tubes one dose of olive oil (control group) and the
      other group was administered one dose of TCDD diluted with olive oil, both at a
      dose of 40 microg/kg body weight. Embryos were removed by cesarean section from
      pregnant mice during the palatal formation stage (GD 13-18) and the palatal form
      was observed using a stereoscopic microscope. In TCDD-exposed embryos, palatal
      fusion was observed on GD 14, 15 and 16 and the incidence of cleft palate was
      100% on GD 18. Fusion rates were 17.5 +/- 15.2% and 12.4 +/- 11.8% on GD 15 and
      16, respectively. Some palates from the TCDD-exposed mouse embryos showed clearly
      developed cleft palate after fusion of the lateral palatine processes during
      palatal formation. A mass of cells, which were chiefly epithelial in the fused
      palates was observed in the TCDD-exposed mouse embryos. A decrease in E-cadherin
      expression was observed in this mass of cells, indicating its involvement in the
      development of cleft palate.

PMID- 20156239
TI  - Brachmann-de Lange syndrome with congenital diaphragmatic hernia and NIPBL gene
      mutation.
AB  - We report herein a case of Brachmann-de Lange syndrome complicated with
      congenital diaphragmatic hernia in which a NIPBL gene mutation was identified. A
      female infant born at 37 weeks of gestation died 134 min after delivery, even
      though endotracheal intubation and resuscitation were performed immediately after
      the scheduled caesarean operation. We diagnosed the infant with Brachmann-de
      Lange syndrome from her physical characteristics. An abnormal peak at the 29th
      exon in the translation area of the NIPBL gene was detected using denaturing high
      performance liquid chromatography. In addition, a mutation of cytosine to thymine
      (nonsense mutation) at the 5524th base was identified using the direct sequence
      method. This variation was likely the cause of the syndrome.

PMID- 20156241
TI  - Online access.

PMID- 20156240
TI  - Alteration in anxiety-related behaviors and reduction of serotonergic neurons in
      raphe nuclei in adult rats prenatally exposed to ethanol.
AB  - It is known that the developing serotonergic system is one of the targets of
      ethanol teratogenicity. Because serotonin has multiple functions in both mature
      and immature brains, disturbance of the serotonergic system by ethanol exposure
      in utero can be cause of a wide range of psychiatric problems in adulthood. In
      the present study, we observed serotonergic neurons in the midbrain raphe nuclei
      and anxiety-like behaviors which would be affected by an altered serotonergic
      system in adult rats prenatally exposed to ethanol. Pregnant rats were fed a
      liquid diet containing 2.5-5.0% (w/v) ethanol on gestational days 10-21. Their
      offspring were examined at 60-70 days of age. A significant decrease in the
      number of serotonergic cells in the midbrain raphe nuclei was shown in prenatally
      ethanol-exposed offspring. In an open field test, they spent more time in a
      central area compared to controls. Also in an elevated plus maze test, prenatally
      ethanol-exposed offspring spent more time on the open arms than controls. These
      behavioral results suggested that prenatally ethanol-exposed rats were less
      sensitive to anxiety. However, 44% of prenatally ethanol-exposed offspring
      exhibited freezing behavior on the open arms of the elevated plus maze, causing
      strong anxiety, compared with 0% in intact control and 12.5% in isocaloric
      sucrose-fed control groups. These findings suggest that prenatal ethanol exposure
      decreases both susceptibility and resistance of anxiety. Insufficient
      serotonergic actions caused by reduced serotonergic neurons in the raphe nuclei
      might contribute to the alterations in anxiety-related behaviors observed in our
      prenatally ethanol-exposed rats.

PMID- 20156242
TI  - Repeatability of subjective evaluation of lameness in horses.
AB  - REASONS FOR PERFORMING STUDY: Previous studies have suggested that agreement
      between equine veterinarians subjectively evaluating lameness in horses is low.
      These studies were limited to small numbers of horses, evaluating movement on the
      treadmill or to evaluating previously-recorded videotape. OBJECTIVES: To estimate
      agreement between equine practitioners performing lameness evaluations in horses
      in the live, over ground setting. METHODS: 131 mature horses were evaluated for
      lameness by 2-5 clinicians (mean 3.2) with a weighted-average of 18.7 years of
      experience. Clinicians graded each limb using the AAEP lameness scale by first
      watching the horse trot in a straight line only and then after full lameness
      evaluation. Agreement was estimated by calculation of Fleiss' (kappa). Evaluators
      agreed if they picked the same limb as lame or not lame regardless of the
      severity of perceived lameness. RESULTS: After only evaluating the horse trot in
      a straight line clinicians agreed whether a limb was lame or not 76.6% of the
      time (kappa= 0.44). After full lameness evaluation clinicians agreed whether a
      limb was lame or not 72.9% of the time (kappa= 0.45). Agreement on forelimb
      lameness was slightly higher than on hindlimb lameness. When the mean AAEP
      lameness score was >1.5 clinicians agreed whether or not a limb was lame 93.1% of
      the time (kappa= 0.86), but when the mean score was < or = 1.5 they agreed 61.9%
      (kappa= 0.23) of the time. When given the task of picking whether or not the
      horse was lame and picking the worst limb after full lameness evaluation,
      clinicians agreed 51.6% (kappa= 0.37) of the time. CONCLUSIONS: For horses with
      mild lameness subjective evaluation of lameness is not very reliable. POTENTIAL
      RELEVANCE: A search for and the development of more objective and reliable
      methods of lameness evaluation is justified and should be encouraged and
      supported.

PMID- 20156243
TI  - Real-time RT-PCR for the detection and quantitative analysis of equine rhinitis
      viruses.
AB  - REASONS FOR PERFORMING STUDY: Equine rhinitis viruses (ERV) cause respiratory
      disease and loss of performance in horses. It has been suggested that the
      economic significance of these viruses may have been underestimated due to
      insensitive methods of detection. OBJECTIVES: To develop a sensitive, rapid, real
      time RT-PCR (rRT-PCR) assay suitable for the routine diagnosis and
      epidemiological surveillance of the A and B variants of ERV. METHODS: TaqMan
      primer probe sets for ERAV and ERBV were designed from conserved regions of the
      5' UTR of the ERV genome. Over 400 samples from both clinically affected and
      asymptomatic horses were employed for validation of the assays. ERAV samples
      positive by rRT-PCR were verified by virus isolation and ERBV positive samples
      were verified by rRT-PCR using a different set of primers. RESULTS: The detection
      limit of the rRT-PCR for both viruses was 10-100 genome copies. Of 250 archival
      nasal swabs submitted for diagnostic testing over a 7 year period, 29 were ERAV
      positive and 3 were ERBV positive with an average incidence rate per year of 10
      and 1.5%, respectively. There was evidence of co-circulation of ERAV and ERBV
      with equine influenza virus (EIV). Of 100 post race urine samples tested, 29 were
      ERAV positive by rRT-PCR. Partial sequencing of 2 ERBV positive samples
      demonstrated that one was 100% identical to ERBV1 from a 270 bp sequence and the
      other was more closely related to ERBV2 than ERBV1 (95% compared to 90%
      nucleotide identity in 178 bp). CONCLUSIONS: The rRT-PCR assays described here
      are specific and more sensitive than virus isolation. They have good
      reproducibility and are suitable for the routine diagnosis of ERAV and ERBV.
      POTENTIAL RELEVANCE: These assays should be useful for investigating the temporal
      association between clinical signs and rhinitis virus shedding.

PMID- 20156244
TI  - Evaluation of current equine welfare issues in Ireland: causes, desirability,
      feasibility and means of raising standards.
AB  - REASONS FOR PERFORMING STUDY: Significant potential threats to the health and
      welfare of horses exist in Ireland when supply exceeds demand and the
      identification system for horses is not yet robust. OBJECTIVES: To secure
      engagement with stakeholder groups and determine their perception of equine
      welfare in Ireland and encourage the development of inclusive, rather than
      imposed, policy solutions. METHODS: A 3 round, web-based Policy Delphi
      incorporating novel vignette methodology was conducted from November 2007-March
      2008 to canvass opinion (in both quantitative and qualitative forms) on the
      perceived most significant equine welfare issues. Vignettes (narratives depicting
      potential compromise to equine welfare) were employed. Quantitative data were
      collected in the form of scoring on a 9 point Likert scale with labelled end
      points, qualitative information as text subsequently analysed for themes.
      RESULTS: All 44 respondents completed all rounds. Major equine welfare issues
      were identified as welfare of horses during the disposal process and at
      unregulated gatherings. Assessed quantitatively on a 9 point Likert scale (0 =
      minimal; 8 = maximal), respondents scored the desirability and feasibility of
      improving standards, median 8 and 6, respectively, for both issues identified.
      Basic themes identified in respondents' quotes as reasons to raise equine welfare
      standards were ideological, protection of animal welfare, safe-guarding the
      reputation of the equine industry and safety (of people, horses and environment).
      Themes for reasons for low standards were societal norms, fiscal pressures,
      indolence, indifference and ignorance. Themes underpinning potential means for
      achieving meaningful change (solutions) were legislation, enforcement,
      education/training, fiscal remedies, increasing awareness and a combination of
      these. CONCLUSIONS: Mechanisms aimed at raising standards must be based on an
      understanding of motivational drivers for currently low standards. POTENTIAL
      RELEVANCE: The challenge is to translate the findings and this heightened
      awareness into meaningful change to the benefit of horses and those who care for
      them.

PMID- 20156245
TI  - The effects of different saddle pads on forces and pressure distribution beneath
      a fitting saddle.
AB  - REASON FOR PERFORMING STUDY: Saddle pads are widely used in riding sports but
      their influence on saddle pressures is poorly understood. OBJECTIVE: To evaluate
      the forces acting on the horse's back, and the eventual pressure distribution by
      using different saddle pads underneath a fitting saddle. METHODS: Sixteen sound
      horses of different breeds and ages were ridden on a treadmill at walk and
      sitting trot. The horses were wearing a dressage saddle with a fitting saddle
      tree and 4 different saddle pads (gel, leather, foam and reindeer fur)
      successively. For comparison, measurements were made without any saddle pad.
      Right forelimb motion was used to synchronise the pressure data with the stride
      cycles. A pressure mat was used under the saddle pad to collect the kinetic data.
      Maximum overall force (MOF) and the pressure distribution in longitudinal and
      transversal direction were calculated to identify differences between the
      measurements with and without saddle pads. RESULTS: A significant decrease in MOF
      was interpreted as improved saddle fit, and a significant increase as worsened
      saddle fit. Only the reindeer fur pad significantly decreased the MOF from 1005 N
      to 796 N at walk and from 1650 N to 1437 N at trot compared to without pad
      measurements. None of the saddle pads increased the MOF significantly when
      compared to the data without saddle pad. The pressure distribution in
      longitudinal and transversal direction was also improved significantly only by
      the reindeer fur pad at trot compared to no pad. CONCLUSION: This study
      demonstrated that a well chosen saddle pad can reduce the load on the horse's
      back and therefore improve the suitability of a fitting saddle.

PMID- 20156246
TI  - A study of the thickness of cheek teeth subocclusal secondary dentine in horses
      of different ages.
AB  - REASONS FOR PERFORMING STUDY: There is limited knowledge on the thickness of
      subocclusal secondary dentine in equine cheek teeth (CT). HYPOTHESES: Subocclusal
      secondary dentine is of consistent thickness above different pulp horns in
      individual horses and its thickness increases with age. METHODS: 408 permanent CT
      were extracted post mortem from 17 horses aged 4-30 years, with no history of
      dental disease. The CT were sectioned longitudinally in the medio-lateral (bucco
      palatal/lingual) plane through each pulp horn, and the thickness of the secondary
      dentine overlying each pulp horn was measured directly. RESULTS: The subocclusal
      thickness of secondary dentine above the pulp horns of CT varied from a mean
      thickness (above all pulp horns) of 12.8 mm (range 5-33 mm) in a 4-year-old to
      7.5 mm (range 2-24 mm) in a 16-year-old horse. There was wide variation in the
      depth of subocclusal secondary dentine above different pulp horns, even within
      the same CT. In contrast to expectations, occlusal secondary dentine thickness
      did not increase with age. There were no significant differences in occlusal
      secondary dentine thickness between rostral and caudal, or medial and lateral
      aspects of the CT, or between contralateral CT. Mandibular CT had significantly
      thicker subocclusal secondary dentine than maxillary CT. Pink coloured secondary
      dentine was sometimes found 1-3 mm occlusal to the pulp horn in sectioned CT and
      this was likely caused by artefactual blood staining from the underlying pulp
      during sectioning. CONCLUSIONS: The thickness of subocclusal secondary dentine
      varies greatly between individual pulp horns, teeth and individual horses and can
      be as low as 2 mm over individual pulp horns. POTENTIAL RELEVANCE: Due to the
      great variation in the thickness of subocclusal secondary dentine between horses,
      and even between pulp horns in individual CT, there is a risk of exposure or
      thermal damage to pulp and thus of apical infection, even with modest therapeutic
      reductions of CT occlusal overgrowths. In the light of these findings, great care
      should be taken when reducing equine CT overgrowths and larger dental overgrowths
      should be reduced in stages.

PMID- 20156247
TI  - Occlusal fissures of the equine cheek tooth: prevalence, location and association
      with disease in 91 horses referred for dental investigation.
AB  - REASON FOR PERFORMING STUDY: Fissures of the occlusal surface of the equine cheek
      tooth are poorly understood and their association with dental disease is unknown.
      OBJECTIVE: To describe the prevalence and location of occlusal fissures in the
      cheek teeth (CT) of a group of horses referred for dental
      investigation/treatment, and determine association with intercurrent dental
      disease. METHODS: Digital video recordings of oral endoscopic examinations for
      all horses referred to the Rossdales Equine Hospital for dental investigation
      from November 2006 to June 2009 were reviewed. Location of occlusal fissures in
      relation to both Triadan tooth position and pulpar secondary dentine was
      recorded; direction of fissure and concurrent involvement of enamel was also
      documented. The CT location considered at the time of examination to be the
      primary site/s of disease was correlated with presence of fissures on these
      teeth. RESULTS: 91 cases meeting the inclusion criteria were identified. Occlusal
      fissures were documented in 58.2% (53/91) cases, with a total of 227 CT being
      affected. Fissures were most prevalent mid-arcade. The majority (92.1%) of
      fissures in maxillary CT were associated with the caudal palatal pulp horn.
      Fissures in mandibular CT were predominantly associated with the buccal pulp
      horns (95.7%). There was no significant difference in the median number of CT
      with fissures in relation to gender. There was no correlation between age (r(2)=
      0.01) of horse and number of CT with fissures. A significantly greater number of
      CT with multiple occlusal fissures was found in mandibular compared to maxillary
      arcades. No correlation was found between presence of fissures and location of
      individual CT considered to be primarily responsible for presentation.
      CONCLUSIONS: Occlusal fissures in this group of animals were common and not
      correlated to primary site of dental disease. POTENTIAL RELEVANCE: In horses
      subjected to dental investigation, occlusal fissures of the cheek teeth should
      not be considered an indicator of tooth compromise. Location and direction of
      fissure propagation in most cases is inconsistent with occlusal fissures being
      causally implicated in slab fractures of cheek teeth, although site predilection
      may indicate a possible association with masticatory forces.

PMID- 20156248
TI  - Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.
AB  - REASONS FOR PERFORMING STUDY: Hyperinsulinaemia is known to induce laminitis
      experimentally in healthy ponies with no history of the condition. Horses are
      more insulin sensitive than ponies and whether prolonged hyperinsulinaemia and
      euglycaemia would have a similar laminitogenic effect requires study. OBJECTIVES:
      To determine if laminitis results when the prolonged euglycaemic
      hyperinsulinaemic clamp technique (p-EHC) is applied to clinically normal
      Standardbred horses, and to monitor hoof wall temperature seeking an association
      between vascular activity and laminitis development. METHODS: Eight young,
      clinically normal Standardbred horses were assigned into 4 pairs and within each
      pair, one was assigned randomly to either treatment (n = 4) or control (n = 4)
      groups. Treated horses received continuous infusions of insulin and glucose until
      clinical signs of laminitis developed, at which point the horses were subjected
      to euthanasia. Control horses received an equivalent volume of a balanced
      electrolyte infusion for the same period. Hoof wall surface temperature (HWST)
      was monitored continuously throughout the experimental period. RESULTS: All
      horses in the treatment group were calculated to have normal insulin sensitivity.
      All treated horses, and none in the control group, developed laminitis (P =
      0.01). Pronounced digital pulses were a feature of the treatment group, while
      insignificant digital pulses occurred in control horses. HWST was higher and less
      variable in treated horses once hyperinsulinaemia was established. CONCLUSIONS:
      Healthy Standardbred horses subjected to prolonged hyperinsulinaemia develop
      laminitis within 48 h, demonstrating that laminitis in horses can be triggered by
      insulin. POTENTIAL RELEVANCE: Insulin resistance and the associated
      hyperinsulinaemia place horses and ponies at risk of developing laminitis. This
      study demonstrates a need for prompt management of the persistent
      hyperinsulinaemia seen in some endocrinopathies.

PMID- 20156249
TI  - Morphological study of tracheal shape in donkeys with and without tracheal
      obstruction.
AB  - REASON FOR PERFORMING STUDY: There is limited information on the gross tracheal
      morphology of donkeys with or without tracheal abnormalities. OBJECTIVES: To: 1)
      examine the morphology of tracheas of donkeys with and without clinical and/or
      post mortem evidence of tracheal obstruction; 2) record the cross-sectional
      dimensions and shapes of tracheal rings at fixed sites; and 3) document
      prevalence, sites and characteristics of detected tracheal abnormalities.
      METHODS: The tracheas of 75, predominantly aged (median age 30 years, range 7-48
      years) donkeys that died or were subjected to euthanasia on humane grounds were
      examined. Five had severe dyspnoea due to tracheal obstruction (with intercurrent
      lung disease in 3), while 7 had post mortem evidence of severe tracheal airway
      obstruction. Every 5th tracheal ring was dissected free and the inner and outer
      vertical and transverse dimensions and cross sectional areas were measured. Each
      dissected ring was photographed and the shape of the trachea was classified as
      normal or, in one of 6 abnormal grades, according to the type and degree of
      structural abnormality present. RESULTS: The tracheas had a mean of 43 (range 34
      50) tracheal rings that tended to be more oval in shape in the distal cervical
      region. Only 31.2% of rings examined had a circular to oval shape. Dorso-ventral
      flattening was present in 0.9% of tracheal rings, dorsal ligament separation in
      24.4%, slight cartilage deformity in 26.0%, moderate cartilage deformity in
      10.4%, marked cartilage deformity in 1.9% and miscellaneous other abnormalities
      in 4.9% of tracheal rings. The 12 donkeys with ante or post mortem evidence of
      tracheal obstruction had significantly increased tracheal abnormality grade in
      comparison to the remaining donkeys. CONCLUSIONS AND POTENTIAL RELEVANCE:
      Structural tracheal abnormalities are present in most old donkeys, but generally
      do not cause clinical problems in these sedentary animals unless intercurrent
      pulmonary disease is present.

PMID- 20156250
TI  - Relationship of horse owner assessed respiratory signs index to characteristics
      of recurrent airway obstruction in two Warmblood families.
AB  - REASONS FOR PERFORMING STUDY: The horse owner assessed respiratory signs index
      (HOARSI-1-4, healthy, mildly, moderately and severely affected, respectively) is
      based on owner-reported clinical history and has been used for the investigation
      of recurrent airway obstruction (RAO) genetics utilising large sample sizes.
      Reliable phenotype identification is of paramount importance in genetic studies.
      Owner reports of respiratory signs have shown good repeatability, but the
      agreement of HOARSI with an in-depth examination of the lower respiratory tract
      has not been investigated. OBJECTIVES: To determine the correlation of HOARSI
      grades 3/4 with the characteristics of RAO and of HOARSI-2 with the
      characteristics of inflammatory airway disease. Further, to test whether there
      are phenotypic differences in the manifestation of lung disease between families.
      METHODS: Seventy-one direct offspring of 2 RAO-affected Warmblood stallions (33
      from the first family, 38 from the second) were graded as HOARSI-1-4 and
      underwent a clinical examination of the respiratory system, arterial blood gas
      analysis, endoscopic mucus scoring, cytology of tracheobronchial secretion (TBS)
      and bronchoalveolar lavage fluid (BALF), and clinical assessment of airway
      reactivity to methacholine chloride. RESULTS: HOARSI-3/4 animals in clinical
      exacerbation showed signs consistent with RAO: coughing, nasal discharge,
      abnormal lung sounds and breathing pattern as well as increased numbers of
      neutrophils in TBS and BALF, excessive mucus accumulation and airway hyper
      responsiveness to methacholine. HOARSI-3/4 horses in remission only had increased
      amounts of tracheal mucus and TBS neutrophil percentages. Clinical phenotypes
      were not significantly different between the 2 families. CONCLUSIONS AND CLINICAL
      RELEVANCE: HOARSI reliably identifies RAO-affected horses in our population.

PMID- 20156251
TI  - Measurement of C-peptide concentrations and responses to somatostatin, glucose
      infusion, and insulin resistance in horses.
AB  - REASONS FOR PERFORMING STUDY: Hyperinsulinaemia is detected in horses with
      insulin resistance (IR) and has previously been attributed to increased
      pancreatic insulin secretion. Connecting peptide (C-peptide) can be measured to
      assess pancreatic function because it is secreted in equimolar amounts with
      insulin and does not undergo hepatic clearance. HYPOTHESIS: A human double
      antibody radioimmunoassay (RIA) detects C-peptide in equine serum and
      concentrations would reflect responses to different stimuli and conditions.
      METHODS: A validation procedure was performed to assess the RIA. Six mature mares
      were selected and somatostatin administered i.v. as a primed continuous rate
      infusion, followed by 50 nmol human C-peptide i.v. Insulin and C-peptide
      concentrations were measured in horses (n = 6) undergoing an insulin-modified
      frequently sampled i.v. glucose tolerance test, and in horses with insulin
      resistance (n = 10) or normal insulin sensitivity (n = 20). RESULTS: A human RIA
      was validated for use with equine sera. Endogenous C-peptide secretion was
      suppressed by somatostatin and median (range) clearance rate was 0.83 (0.15-1.61)
      ml/min/kg bwt. Mean + or - s.d. C-peptide-to-insulin ratio significantly (P =
      0.004) decreased during the glucose tolerance test from 3.60 + or - 1.95 prior to
      infusion to 1.03 + or - 0.18 during the first 20 min following dextrose
      administration. Median C-peptide and insulin concentrations were 1.5- and 9.5
      fold higher, respectively in horses with IR, compared with healthy horses.
      CONCLUSIONS: Endogenous C-peptide secretion decreases in response to somatostatin
      and increases after dextrose infusion. Results suggest that relative insulin
      clearance decreases as pancreatic secretion increases in response to dextrose
      infusion. Hyperinsulinaemia in insulin resistant horses may be associated with
      both increased insulin secretion and decreased insulin clearance. POTENTIAL
      RELEVANCE: Both C-peptide and insulin concentrations should be measured to assess
      pancreatic secretion and insulin clearance in horses.

PMID- 20156252
TI  - Return to work following unilateral enucleation in 34 horses (2000-2008).
AB  - REASONS FOR STUDY: The effect of unilateral enucleation on vision and potential
      loss of performance in horses has received little study. OBJECTIVE: To evaluate
      the likelihood of return to prior discipline following unilateral enucleation in
      horses, assessing the role of age at enucleation, equine discipline, reason for
      enucleation, time to vision loss and eye enucleated. HYPOTHESIS: Unilateral
      enucleation has no significant effect on likelihood of return to work in horses,
      for both right and left eyes, across age and discipline. METHOD: A retrospective
      review of medical records identified 92 horses that underwent unilateral
      enucleation at the University of Pennsylvania New Bolton Center from April 2000
      April 2008. Case variables determined from the medical record included breed and
      sex of horse, age at enucleation, which eye was enucleated, reason for
      enucleation and onset of vision loss. Pre- and post operative occupations were
      determined by telephone interview with the owner or trainer of each horse.
      RESULTS: Based on hospital surgery logs, 92 enucleations were performed over the
      8 year period and 77 records were available for review, with follow-up
      information available for 34 horses. Of these, 29/34 (85%) horses returned to
      work in pleasure or trail riding (11/13), flat racing (7/10), hunter/jumpers
      (4/4), dressage (3/3), group lessons (1/1), eventing (1/1), steeplechase (1/1)
      and as a broodmare (1/1). Four of 5 horses (4/34, or 12% sample) that did not
      return to work (2 pleasure and 2 racing) were retired due to anticipated or
      perceived decrease in performance or behaviour change following unilateral
      enucleation, with the remaining horse retired from racing for lameness issues
      unrelated to enucleation. Twenty-two of 25 horses (88%) with acute vision loss
      and 7/9 horses (78%) with gradual vision loss returned to their previous
      discipline. CONCLUSIONS: Horses are able to return to a variety of occupations
      after unilateral enucleation.

PMID- 20156253
TI  - A survey on two years of medication regulation in horse races in Iran.
AB  - REASONS FOR PERFORMING STUDY: The present survey evaluated the use of prohibited
      substances cases in the first 2 years of medication regulation in horseracing in
      Iran so that the impact of these regulations on the level of positive cases over
      the period could be assessed. OBJECTIVES: To determine the prevalence of positive
      tests for prohibited substances in horse races during 2 years of a drugs testing
      programme in Iran. METHODS: A total of 656 horses that were winners or second in
      races were tested during the 2 year study. In the first year 354 horses (209
      males and 145 females) and in the second year 302 horses (155 males and 147
      females) were tested. In the 2 years, 306 were found to be positive. Urine
      samples were taken from candidate horses and sent to the Central Doping
      Laboratory. Blood samples were taken from those horses where a urine sample could
      not be taken within one hour. Detection and measurement of prohibited substances
      were carried out by ELISA, GC and HPLC using standard methods. RESULTS: Thirty
      two percent of males were positive for prohibited substances, which was not
      significantly different from the percentage of females (25.5%). In the second
      year, of the 302 horses tested for prohibited substances, 33.5% of males were
      positive, again similar to females (33.3%). Almost 83% of horses tested positive
      for prohibited substances once in the first year, 15% tested positive twice and
      2% tested positive 3 times. In the second year 78% tested positive once, 15%
      tested positive twice and 7% tested positive 3 times. Morphine was the most used
      prohibited substance and was detected 42 times during the survey, followed by
      caffeine and phenylbutazone. Morphine was also the most used drug in combination
      with other drugs in both years. CONCLUSIONS: Morphine and caffeine were the most
      popular prohibited substances found in the measurements. As these substances were
      found in the environment and food stuffs, their presence in the samples may be
      due to unintentional feeding of contaminated materials (bread, hay and
      chocolate).

PMID- 20156254
TI  - Clinical and imaging features of suspected prodromal fracture of the proximal
      phalanx in three Thoroughbred racehorses.
AB  - Sagittal fracture of the proximal phalanx (P1) is an important musculoskeletal
      injury of the performance horse. Although widely considered to be monotonic in
      nature, there is emerging evidence that some P1 fractures may have stress-injury
      aetiology. Three cases are described in which imaging features found were
      suggestive of prodromal bone injury. All cases returned to full performance use
      after a period of rest. The authors conclude that it is possible that some P1
      fractures in the Thoroughbred racehorse may develop through stress/fatigue injury
      pathways. It is proposed that intervention prior to overt fracture may be
      possible in some cases.

PMID- 20156255
TI  - Dysautonomia in a six-year-old mule in the United States.
AB  - Equine dysautonomia, also known as equine grass sickness (EGS), is a well
      documented disease in several countries. To the authors' knowledge, EGS has not
      been reported previously in North America. This report describes EGS in a 6-year
      old female mule in the USA. Failure initially to consider EGS resulted in a
      delayed diagnosis. EGS should be considered as a differential diagnosis and
      appropriate diagnostic tests performed in similar cases in North America.

PMID- 20156256
TI  - A review of tendon injury: why is the equine superficial digital flexor tendon
      most at risk?
AB  - Tendon injury is one of the most common causes of wastage in the performance
      horse; the majority of tendon injuries occur to the superficial digital flexor
      tendon (SDFT) whereas few occur to the common digital extensor tendon. This
      review outlines the epidemiology and aetiology of equine tendon injury, reviews
      the different functions of the tendons in the equine forelimb and suggests
      possible reasons for the high rate of failure of the SDFT. An understanding of
      the mechanisms leading to matrix degeneration and subsequent tendon gross failure
      is the key to developing appropriate treatment and preventative measures.

PMID- 20156257
TI  - Detection and genetic characterisation of vanA-containing Enterococcus strains in
      healthy Lusitano horses.
AB  - Lusitano horses were investigated in order to detect the presence of vancomycin
      resistant enterococci. vanA isolates showed high level vancomycin (Minimum
      inhibitory concentration; MIC > or = 128 mg/l) and teicoplanin resistance (MIC 64
      mg/l), as well as resistance to ciprofloxacin, erythromycin and tetracycline. The
      tet(L) and erm(B) genes, associated with tetracycline and erythromycin
      resistance, respectively, were found in all vanA isolates. The intestinal tract
      of Lusitano horses can be a potential reservoir for vanA-containing enterococci.

PMID- 20156258
TI  - N-Desmethylclozapine exerts dual and opposite effects on salivary secretion in
      the rat.
AB  - N-Desmethylclozapine is a major metabolite of the atypical antipsychotic drug
      clozapine, used in the treatment of therapy-resistant schizophrenia. Patients
      under clozapine treatment report a troublesome sialorrhea. Recent experiments
      show clozapine to exert mixed agonist/antagonist actions on salivary secretion in
      rats. The present study was performed to define the secretory role of N
      desmethylclozapine and to compare it with that of its parent compound. N
      Desmethylclozapine evoked secretion by acting directly on the muscarinic
      acetylcholine M1-receptors of 'silent' duct-cannulated parotid and submandibular
      glands of the anaesthetized rat. In chronic surgically denervated glands, the
      secretory response was enlarged. The methacholine-evoked secretion, as well as
      the parasympathetic nerve-evoked secretion, were reduced by N-desmethylclozapine
      and involved blockade of M3-receptors, while the sympathetic nerve-evoked
      response was reduced, involving blockade of alpha(1)-adrenergic receptors.
      Synergistic interactions between N-desmethylclozapine and the beta-adrenergic
      receptor agonist, isoprenaline, occurred. Compared with clozapine, the excitatory
      efficacy of N-desmethylclozapine was higher and the inhibitory efficacy was lower
      (parasympathetic activity) or about the same (sympathetic activity).
      Theoretically, in humans treated with clozapine, an increase in the N
      desmethylclozapine : clozapine ratio would contribute to salivation during the
      night and at rest, and, furthermore, the magnitude of the reduction in the
      reflexly elicited secretion is likely to diminish.

PMID- 20156259
TI  - Aquaporin 11 in the developing mouse submandibular gland.
AB  - Several aquaporins (AQPs) have been detected in mature and embryonic mammalian
      salivary glands (AQP1 and AQP3-AQP8). However, AQP11 has, to our knowledge, never
      before been described in salivary glands, but is known to be important in, for
      example, kidney development in mice. We therefore thought it relevant to
      investigate if AQP11 was present during salivary organogenesis. The submandibular
      salivary gland (SMG) from CD1 mice was studied during prenatal development and
      early postnatal development, and also in young adult male and female mice. The
      expression trend of the AQP11 transcript was detected using the reverse
      transcription-polymerase chain reaction (RT-PCR), and the temporal-spatial
      pattern was observed using in situ hybridization. The AQP11 transcript was first
      detected at embryonic day 13.5 and showed a more or less constitutive expression
      trend during the prenatal and early postnatal SMG development. Spatial studies
      demonstrated that the AQP11 transcript was present in the developing and mature
      duct structures at all stages studied. In the end pieces, the AQP11 transcript
      was reduced during glandular development. Our results point to an important role
      for AQP11 during salivary gland development.

PMID- 20156260
TI  - Ultrastructural localization of salivary mucins MUC5B and MUC7 in human labial
      glands.
AB  - As a result of their presence throughout the mouth in the submucosa or between
      muscle fibers, minor salivary glands secrete directly and continuously into the
      oral cavity, providing mucosal surfaces with highly glycosylated proteins that
      are active in bacterial aggregation and in oral tissue lubrication. In this
      study, we investigated the ultrastructural localization of the MUC5B and MUC7
      mucins in human labial glands by means of a postembedding immunogold technique.
      Thin sections of normal human labial glands, obtained during surgery, were
      incubated with polyclonal antibodies to human salivary mucins MUC5B and MUC7, and
      then with gold-labeled secondary antibodies. Specific MUC5B reactivity was found
      in the secretory granules of mucous cells of all glands examined, and was
      associated with the luminal membrane of duct cells. MUC7 labeling was observed in
      the granules of both mucous and seromucous secretory cells of the glandular
      parenchyma. Quantitative analyses demonstrated that seromucous granules have
      higher immunogold labeling densities for MUC7 than mucous granules. Our
      immunohistochemical data extend the results of previous light microscopic studies
      of MUC5B and MUC7 localizations, pointing out the significant contribution of
      human labial glands in the secretion process of these two mucins.

PMID- 20156261
TI  - Down-regulation of expression of osteoblast and osteocyte markers in periodontal
      tissues associated with the spontaneous alveolar bone loss of interleukin-10
      knockout mice.
AB  - The aim of this study was to unravel the mechanisms by which interleukin (IL)-10,
      a potent pleiotropic cytokine, modulates alveolar bone homeostasis in C57BL/6
      wild-type (WT) and IL-10 knockout (IL-10 KO) mice, evaluated at 8, 24, and 48 wk
      of age. Interleukin-10 KO mice presented significant alveolar bone loss when
      compared with WT mice, and this was not associated with changes in leukocyte
      counts or bacterial load. The levels of expression of messenger RNA (mRNA) for
      tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, transforming growth
      factor-beta (TGF-beta), receptor activator of nuclear factor kappaB ligand
      (RANKL), osteoprotegerin (OPG), and matrix metalloproteinase 13 (MMP13) were
      similar between both strains, whereas a significant decrease of tissue inhibitor
      of metalloproteinase 1 (TIMP1) mRNA expression was found at 48 wk in IL-10 KO
      mice. The osteoblast markers core binding factor alpha1 (CBFA1) and type I
      collagen (COL-I) were expressed at similar levels in both strains, whereas the
      levels of alkaline phosphatase (ALP) and osteocalcin (OCN), and those of the
      osteocyte markers phosphate-regulating gene endopeptidases (PHEX) and dentin
      matrix protein 1 (DMP1) were significantly lower in IL-10 KO mice. Our results
      demonstrate that the alveolar bone loss in the absence of IL-10 was associated
      with a reduced expression of osteoblast and osteocyte markers, an effect
      independent of microbial, inflammatory or bone-resorptive pathways.

PMID- 20156262
TI  - Mechanosensitivity of dental pulp stem cells is related to their osteogenic
      maturity.
AB  - For engineering bone tissue, mechanosensitive cells are needed for bone
      (re)modelling. Local bone mass and architecture are affected by mechanical
      loading, which provokes a cellular response via loading-induced interstitial
      fluid flow. We studied whether human dental pulp-derived mesenchymal stem cells
      (PDSCs) portraying mature (PDSC-mature) or immature (PDSC-immature) bone cell
      characteristics are responsive to pulsating fluid flow (PFF) in vitro. We also
      assessed bone formation by PDSCs on hydroxyapatite-tricalcium phosphate granules
      after subcutaneous implantation in mice. Cultured PDSC-mature exhibited higher
      osteocalcin and alkaline phosphatase gene expression and activity than PDSC
      immature. Pulsating fluid flow (PFF) stimulated nitric oxide production within 5
      min by PDSC-mature but not by PDSC-immature. In PDSC-mature, PFF induced
      prostaglandin E(2) production, and cyclooxygenase 2 gene expression was higher
      than in PDSC-immature. Implantation of PDSC-mature resulted in more osteoid
      deposition and lamellar bone formation than PDSC-immature. We conclude that PDSCs
      with a mature osteogenic phenotype are more responsive to pulsating fluid shear
      stress than osteogenically immature PDSCs and produce more bone in vivo. These
      data suggest that PDSCs with a mature osteogenic phenotype might be preferable
      for bone tissue engineering to restore, for example, maxillofacial defects,
      because they might be able to perform mature bone cell-specific functions during
      bone adaptation to mechanical loading in vivo.

PMID- 20156263
TI  - Increased vitamin D-driven signalling and expression of the vitamin D receptor,
      MSX2, and RANKL in tooth resorption in cats.
AB  - Tooth resorption occurs in 20-75% of cats (Felis catus). The aetiology is not
      known, but vitamin D is suggested to be involved. Vitamin D acts through a
      nuclear receptor (VDR) and increases the expression of receptor activator of
      nuclear factor-kappaB ligand (rankl) and muscle segment homeobox 2 (msx2) genes.
      Mice lacking the muscle segment homeobox 2 (msx2) gene show decreased levels of
      rankl, suggesting an interaction among VDR, MSX2, and RANKL. Here, we
      investigated the expression of VDR, MSX2, and RANKL proteins, and the activity of
      the VDR-mediated signalling pathway (using the quantitative polymerase chain
      reaction on VDR target genes), in tooth resorption, and measured the serum levels
      of vitamin D metabolites in cats. Tooth resorption was categorized into either
      resorptive or reparative stages. In the resorptive stage, odontoclasts expressed
      MSX2 and RANKL (100% and 88%, respectively) and fibroblasts expressed VDR and
      MSX2 (both at 100%), whereas fibroblasts expressed RANKL in only 29% of the sites
      analysed. In the reparative stage, cementoblasts expressed VDR, MSX2, and RANKL,
      whereas fibroblasts expressed VDR and MSX2, but not RANKL. The vitamin D status
      did not differ between the groups, based on the serum levels of 25
      hydroxycholecalciferol. However, increased expression of VDR protein, and the
      relative gene expression levels of 1alpha-hydroxylase and the VDR-target gene, 24
      hydroxylase, indicated the involvement of an active vitamin D signalling in the
      pathophysiology of tooth resorption in cats.

PMID- 20156264
TI  - Tooth agenesis patterns in bilateral cleft lip and palate.
AB  - Individuals with cleft lip and palate present significantly more dental
      anomalies, even outside the cleft area, than do individuals without clefts. Our
      aim was to evaluate the prevalence of tooth agenesis and patterns of hypodontia
      in a large sample of patients with complete bilateral cleft lip and palate
      (BCLP). Serial panoramic radiographs (the first radiograph was taken at 10.5-13.5
      yr of age) of 240 patients with BCLP (172 male patients, 68 female patients) were
      examined. Third molars were not included in the evaluation. Agenesis of at least
      one tooth was present in 59.8% of patients. Upper laterals and upper and lower
      second premolars were missing most frequently. Using the tooth agenesis code
      (TAC), 52 different agenesis patterns were identified, of which simultaneous
      agenesis of 12, 22, 15, 25, 35, and 45 was the most frequent pattern. Nine of the
      240 patients showed combined BCLP and oligodontia.

PMID- 20156265
TI  - Partially erupted third molars as a potential source of infection in patients
      receiving peripheral stem cell transplantation for malignant diseases: a
      retrospective study.
AB  - Forty-four patients with malignant diseases for which they received peripheral
      stem cell transplant therapy (PSCT) were retrospectively studied regarding local
      and systemic infection originating from around partially erupted third molars
      (PEMs). Twenty-two patients had one or more PEMs, while 22 patients had none.
      Data were retrieved from medical and dental records. Systemic and local signs of
      infection and treatment were assessed. We recorded the number of transplanted
      CD34(+) blood stem cells, days with white blood cell counts < 0.5 x 10(9) l(-1),
      days until engraftment, maximum level of C-reactive protein (CRP), days with
      fever, positive blood cultures, days taking antibiotics, days drinking < 0.5 l,
      days of total parenteral nutrition, days receiving intravenously administered
      analgesics, and number of admission days. No statistically significant difference
      was detected between patients with PEMs and those without PEMs regarding any of
      the studied parameters. Of patients with PEMs, 36% (8 of 22) developed local
      infections around PEMs during the PSCT period. The study indicates that PEMs pose
      no significant risk of causing systemic infection in patients receiving PSCT for
      malignant diseases but increase the risk of developing a local infection,
      justifying close supervision and early treatment in cases of local infection
      during PSCT treatment.

PMID- 20156266
TI  - The relationship between dental anxiety and dental decay experience in antenatal
      mothers.
AB  - The aim of this study was to investigate the relationship between dental anxiety
      and dental decay experience among antenatal mothers attending Maternal and Child
      Health clinics in Malaysia. A cross-sectional study was conducted on a
      consecutive sample of 407 antenatal mothers in Seremban, Malaysia. The
      questionnaire consisted of participants' demographic profile and the Dental Fear
      Survey. The D(3cv)MFS was employed as the outcome measure and was assessed by a
      single examiner (intraclass correlation = 0.98). A structural equation model was
      designed to inspect the relationship between dental anxiety and dental decay
      experience. The mean Dental Fear Survey score for all participants was 35.1 [95%
      confidence interval (34.0, 36.3)]. The mean D(3cv)MFS score was 10.8 [95%
      confidence interval (9.5, 12.1)]. Participants from low socio-economic status
      groups had significantly higher D(3cv)MFS counts than those from high socio
      economic status groups. The path model with dental anxiety and socio-economic
      status as predictors of D(3cv)MFS showed satisfactory fit. The correlation
      between dental anxiety and dental decay experience was 0.30 (standardized
      estimate), indicating a positive association. Socio-economic status was also
      statistically significantly associated with the D(3cv)MFS count (beta = 0.19).
      This study presented robust evidence for the significant relationship between
      dental anxiety and dental decay experience in antenatal mothers.

PMID- 20156267
TI  - Satisfaction with teeth and life-course predictors: a prospective study of a
      Swedish 1942 birth cohort.
AB  - This study aimed to assess the stability or change in satisfaction with teeth
      among Swedish adults between the ages of 50 and 65 yr, and to identify the impact
      of socio-demographics and of clinical and subjective oral health indicators on
      participants' satisfaction with teeth during that period. Self-administered
      standardized questionnaires were used as part of a longitudinal study. In 1992,
      1997, 2002, and 2007 all residents (born in 1942) of two Swedish counties were
      invited to participate in the study. A total of 63% women and 66% men reported
      being satisfied with their teeth between 50 and 65 yr of age. The corresponding
      figures, with respect to dissatisfaction, were 7% and 6% respectively.
      Generalized estimated equation models revealed a decline in the odds of being
      satisfied with advancing age, which was particularly important in subjects with
      lower education, tooth loss, and smokers. Consolidation in oral health
      perceptions starts before age 50, suggesting early intervention before that age.
      Promotion of a healthy adult lifestyle and improved access to quality oral
      healthcare might increase the likelihood of people being satisfied with their
      teeth throughout the third age-period in both genders.

PMID- 20156268
TI  - A confocal micro-endoscopic investigation of the relationship between the
      microhardness of carious dentine and its autofluorescence.
AB  - This study aimed to investigate the null hypothesis that there is no relationship
      between the microhardness of carious dentine and its native autofluorescence
      (AF). Six extracted, carious molars were sectioned through natural lesions in the
      mesio-distal longitudinal plane. The Knoop microhardness (Knoop hardness number,
      KHN) of the cut surfaces of each sample was recorded at regular intervals through
      sound and carious dentine. Confocal fibre-optic micro-endoscopic (CFOME)
      examination of the carious dentine and the sound dentine was carried out at the
      same intervals using the Cellvizio system (600 microm wide, flat-end probe) with
      an excitation wavelength of 488 nm. The blindly collected numerical data were
      analysed using the original microhardness KHN. The data analysis indicated that
      the autofluorescence signals increased significantly when the microhardness of
      dentine dropped below 25 KHN. Therefore, the null hypothesis was disproved, and
      it was concluded from this investigation that the autofluorescent signal
      intensity recorded using CFOME could produce an objective and reproducible
      correlation to the microhardness of carious dentine. Confocal fibre-optic micro
      endoscopic examination could have clinical potential as a technology to help
      delineate the carious dentine that might be excavated in a clinical procedure in
      vivo.

PMID- 20156269
TI  - Dentin treatment effects on the bonding performance of self-adhesive resin
      cements.
AB  - The effects of dentin surface treatments on the microtensile bond strengths and
      on the interfacial characteristics of self-adhesive resin cements were
      investigated. Flat dentin surfaces were obtained from human molars and were
      treated as follows: (i) no treatment of dentin; (ii) 0.1 M EDTA scrubbed for 60
      s; or (iii) 10% polyacrylic acid applied for 30 s. Three self-adhesive cements
      were used to lute composite overlays on deep-coronal dentin surfaces in the
      presence of simulated pulpal pressure (15 cm of H(2)O). Bonded specimens were cut
      into beams 1 mm thick and stressed in tension until failure. Fractured sticks
      were examined under a scanning electron microscope. Additional specimens were
      stained with Masson's trichrome and observed under light microscopy for
      interfacial evaluations. The bond strength to dentin of the hydrophobic and
      solvent-free cement (RelyX Unicem) was unaffected by the tested dentin
      treatments. The bond strength of the 2-hydroxyethyl methacrylate (HEMA)-based
      cement (Bis-Cem) decreased after treatment of dentin with EDTA and/or polyacrylic
      acid. The hydrophilic and water-containing cement (G-Cem) attained a higher bond
      strength when luted on polyacrylic acid-conditioned dentin. In conclusion, smear
      layer removal, opening of dentinal tubules, and the water content of dentin
      differently influence the bond strengths and the interfacial characteristics of
      self-adhesive cement-dentin interfaces.

PMID- 20156270
TI  - Finite element and Weibull analyses to estimate failure risks in the ceramic
      endocrown and classical crown for endodontically treated maxillary premolar.
AB  - The present study evaluated the failure risks of an endodontically treated
      premolar with severely damaged coronal hard tissue and restored with either a
      computer-aided design/computer-aided manufacturing (CAD/CAM) ceramic endocrown or
      a classical crown configuration. Two, three-dimensional finite element maxillary
      premolar models were designed with endodontic treatment and restored with either
      a chairside economic reconstruction of esthetic ceramic (CEREC) ceramic endocrown
      or a classical crown. The Weibull function was incorporated with finite element
      analysis to calculate the long-term failure probability relative to different
      load conditions. Additionally, an in vitro fatigue-load fracture experiment was
      performed to validate the numerical simulation results. The results indicated
      that the stress values on the dentin and luting cement for the endocrown
      restoration were lower than those for the crown configuration. Weibull analysis
      revealed that the individual failure probability in the endocrown dentin and
      luting cement diminished more than those for the crown restoration. While the
      overall failure probabilities for the endocrown and the classical crown were
      similar, fatigue fracture testing revealed that the endocrown restoration had
      higher fracture resistance than the classical crown configuration (1,446 vs.
      1,163 MPa). This investigation implies that the endocrown can be considered as a
      conservative, aesthetic, and clinically feasible restorative approach for
      endodontically treated maxillary premolars.

PMID- 20156271
TI  - Measurements of volatile compound contents in resins using a moisture analyzer.
AB  - The contents of volatile adhesive compounds, such as water, solvents, and
      residual unpolymerized monomers, affect the integrity and durability of adhesive
      bonding. However, there is no method available that can be used to rapidly assess
      the residual solvent or water contents of adhesive resins. This study examined
      the effectiveness of a digital moisture analyzer to measure the volatile compound
      contents of resins. Five self-etching adhesives and seven experimental light
      cured resins prepared with different contents (0, 10, and 20% by weight) of water
      or solvents (acetone and ethanol) were examined in this study. The resins were
      prepared using different methods (with and without air blast or light-curing) to
      simulate the clinical conditions of adhesive application. Resin weight changes (%
      of weight loss) were determined as the residual volatile compound contents, using
      the moisture analyzer. After the measurements, the resin films were examined
      using a scanning electron microscope. The weight changes of the resins were found
      to depend on the amount of water or solvents evaporating from the resin. Water
      and solvents were evaporated by air blast or light-curing, but some of the water
      and solvents remained in the cured resin. The moisture analyzer is easy to
      operate and is a useful instrument for using to measure the residual volatile
      compound contents of adhesive resin.

PMID- 20156272
TI  - Elution of substances from a silorane-based dental composite.
AB  - Previous studies have shown that residual monomers, initiators, and additives are
      eluted from methacrylate-based dental composite materials. Recently, a composite
      material (Filtek Silorane), based on a new resin chemistry, was introduced. The
      purpose of this study was to investigate substances eluted from Filtek Silorane
      in water and ethanol. Polymerized specimen discs of the material were immersed in
      either distilled water or 75 vol% ethanol at 37 degrees C, and the solutions were
      analyzed using liquid chromatography-mass spectrometry after 1, 4, 24, and 72 h
      eluting time. No substances were found to leach from Filtek Silorane in water,
      whereas silorane monomers and an initiator component were eluted from the
      material into the ethanol solution.

PMID- 20156276
TI  - Inordinate fondness for prolegs.

PMID- 20156278
TI  - Integrative analysis of polychaete ontogeny: cell proliferation patterns and
      myogenesis in trochophore larvae of Sabellaria alveolata.
AB  - Aspects of muscle development are still widely neglected in studies on
      invertebrate ontogeny, which is probably at least partly due to the inherent
      complexity of animal myoanatomical bodyplans. This has resulted in significant
      gaps in our understanding of the evolutionary and ontogenetic origin of this
      crucial mesoderm-derived organ system, particularly in indirect developing
      representatives of the Lophotrochozoa. Here, we document the temporal and spatial
      patterns of muscle formation and cell proliferation in the polychaete Sabellaria
      alveolata during planktotrophic larval development in order to assess the
      presumed generation of muscle units and segments from a posterior growth zone. In
      addition, we address the question whether the three primary segments differ in
      their mode of myogenesis from the subsequently forming segments. We found that in
      the first three segments the ventral transverse muscles differentiate from
      anterior to posterior, whereas the ventral oblique muscles develop
      simultaneously. Hence, subsequent and simultaneous developmental processes of
      specific muscle groups are possibly regulated in different ways, thus emphasizing
      the plasticity of the formation of metamerically arranged organ systems in
      polychaetes. The occurrence of three clusters of proliferating cells in the trunk
      region of the metatrochophore indicates synchronous subdivision of the larval
      mesoderm in the first three segments. Assuming a polychaete-like ancestor at the
      base of the annelid tree, comparative analysis suggests that the bodywall of the
      last common annelid ancestor might have been devoid of circular muscles and
      consisted of four separate longitudinal muscle strands that develop from anterior
      to posterior.

PMID- 20156279
TI  - Neuromuscular development in Novocrania anomala: evidence for the presence of
      serotonin and a spiralian-like apical organ in lecithotrophic brachiopod larvae.
AB  - The phylogenetic position of Brachiopoda remains unsettled, and only few recent
      data on brachiopod organogenesis are currently available. In order to contribute
      data to questions concerning brachiopod ontogeny and evolution we investigated
      nervous and muscle system development in the craniiform (inarticulate) brachiopod
      Novocrania anomala. Larvae of this species are lecithotrophic and have a bilobed
      body with three pairs of dorsal setal bundles that emerge from the posterior
      lobe. Fully developed larvae exhibit a network of setae pouch muscles as well as
      medioventral longitudinal and transversal muscles. After settlement, the anterior
      and posterior adductor muscles and delicate mantle retractor muscles begin to
      form. Comparison of the larval muscular system of Novocrania anomala with that of
      rhynchonelliform (articulate) brachiopod larvae shows that the former has a much
      simpler muscular organization. The first signal of serotonin-like
      immunoreactivity appears in fully developed Novocrania anomala larvae, which have
      an apical organ that consists of four flask-shaped cells and two ventral
      neurites. These ventral neurites do not stain positively for the axonal marker
      alpha-tubulin in the larval stages. In the juveniles, the nervous system stained
      by alpha-tubulin is characterized by two ventral neurite bundles with three
      commissures. Our data are the first direct proof for the presence of an
      immunoreactive neurotransmitter in lecithotrophic brachiopod larvae and
      demonstrate the existence of flask-shaped serotonergic cells in the brachiopod
      larval apical organ, thus significantly increasing the probability that this cell
      type was part of the bauplan of the larvae of the last common lophotrochozoan
      ancestor.

PMID- 20156280
TI  - Squid vascular endothelial growth factor receptor: a shared molecular signature
      in the convergent evolution of closed circulatory systems.
AB  - The highly specialized cephalopod cardiovascular system has long been considered
      a valuable model for understanding the evolution of circulatory systems. Despite
      the number of studies devoted to this topic, the developmental regulatory
      mechanisms remain largely unexplored. Here, we focus on the vascular endothelial
      growth factor receptor (VEGFR). This factor is known to mediate levels of
      endothelial growth factor that is involved in hematopoiesis and vasculogenesis
      including multichambered heart development in vertebrates. We found a squid VEGFR
      ortholog that is expressed in the developing blood vessels, notably in the sheet
      like endothelial cells of the systemic and branchial hearts. The highly
      restricted localization of VEGFR in the vascular endothelial cells and its shared
      expression pattern in the developing hearts of cephalopods and vertebrates
      suggest a shared molecular signature of closed circulatory systems that has been
      independently elaborated during evolution.

PMID- 20156281
TI  - Mechanisms of heart development in the Japanese lamprey, Lethenteron japonicum.
AB  - Vertebrate hearts have evolved from undivided tubular hearts of chordate
      ancestors. One of the most intriguing issues in heart evolution is the abrupt
      appearance of multichambered hearts in the agnathan vertebrates. To explore the
      developmental mechanisms behind the drastic morphological changes that led to
      complex vertebrate hearts, we examined the developmental patterning of the
      agnathan lamprey Lethenteron japonicum. We isolated lamprey orthologs of genes
      thought to be essential for heart development in chicken and mouse embryos,
      including genes responsible for differentiation and proliferation of the
      myocardium (LjTbx20, LjTbx4/5, and LjIsl1/2A), establishment of left-right heart
      asymmetry (LjPitxA), and partitioning of the heart tube (LjTbx2/3A), and studied
      their expression patterns during lamprey cardiogenesis. We confirmed the presence
      of the cardiac progenitors expressing LjIsl1/2A in the pharyngeal and splanchnic
      mesoderm and the heart tube of the lamprey. The presence of LjIsl1/2A-positive
      cardiac progenitor cells in cardiogenesis may have permitted an increase of
      myocardial size in vertebrates. We also observed LjPitxA expression in the left
      side of lamprey cardiac mesoderm, suggesting that asymmetric expression of Pitx
      in the heart has been acquired in the vertebrate lineage. Additionally, we
      observed LjTbx2/3A expression in the nonchambered myocardium, supporting the view
      that acquisition of Tbx2/3 expression may have allowed primitive tubular hearts
      to partition, giving rise to multichambered hearts.

PMID- 20156282
TI  - Role of Hox PG2 genes in Nile tilapia pharyngeal arch specification: implications
      for gnathostome pharyngeal arch evolution.
AB  - Phylogenetic reconstructions suggest that the ancestral osteichthyan Hox paralog
      group 2 gene complement was composed of two genes, Hoxa2 and b2, both of which
      have been retained in tetrapods, but only one of which functions as a selector
      gene of second pharyngeal arch identity (PA2). Genome duplication at the
      inception of the teleosts likely generated four Hox PG2 genes, only two of which,
      hoxa2b and b2a, have been preserved in zebrafish, where they serve as
      functionally redundant PA2 selector genes. Evidence from our laboratory has shown
      that other telelosts, specifically striped bass and Nile tilapia, harbor three
      transcribed Hox PG2 genes, hoxa2a, a2b, and b2a, with unspecified function(s). We
      have focused on characterizing the function of the three Nile tilapia Hox PG2
      genes as a model to examine the effects of postgenome duplication gene loss on
      the evolution of developmental gene function. We studied Hox PG2 gene function in
      tilapia by examining the effects of independent morpholino oligonucleotide (MO)
      induced knockdowns on pharyngeal arch morphology and Hox gene expression
      patterns. Morphological defects resulting from independent MO-induced knockdowns
      of tilapia hoxa2a, a2b, and b2a included the expected PA2 to PA1 homeotic
      transformations previously observed in tetrapods and zebrafish, as well as
      concordant and unexpected morphological changes in posterior arch-derived
      cartilages. Of particular interest, was the observation of a MO-induced
      supernumerary arch between PA6 and PA7, which occurred concomitantly with other
      MO-induced pharyngeal arch defects. Beyond these previously unreported morphant
      induced transformations, a comparison of Hox PG2 gene expression patterns in
      tilapia Hox PG2 morphants were indicative of arch-specific auto- and cross
      regulatory activities as well as a Hox paralog group 2 interdependent regulatory
      network for control of pharyngeal arch specification.

PMID- 20156283
TI  - GRAMINIFOLIA homolog expression in Streptocarpus rexii is associated with the
      basal meristems in phyllomorphs, a morphological novelty in Gesneriaceae.
AB  - Streptocarpus is a genus showing great variation in vegetative plant architecture
      and hence provides an attractive system to study the evolution of morphological
      diversity. Besides species showing an orthodox caulescent plant organization,
      producing leaves from a conventional shoot apical meristem (SAM), there are
      species whose body plan is composed of units (phyllomorphs) consisting of a
      petiole-like structure and a lamina that has the ability of continued growth. The
      first of these units is the macrocotyledon, derived from the continued growth of
      one of the two cotyledons by the activity of a basal meristem (BM), whereas
      further phyllomorphs develop from a SAM-like meristem. We carried out anatomical
      and morphological studies on the macrocotyledon of Streptocarpus rexii showing
      that the lamina has a bifacial structure, whereas the petiolode is partially
      unifacial. YABBY transcription factors are known to be involved in organ polarity
      and also promote lamina growth. We characterized the expression of SrGRAM, an
      ortholog of the YABBY genes GRAMINIFOLIA (GRAM) and FILAMENTOUS FLOWER (FIL), in
      S. rexii by in situ hybridization and RT-PCR. Gene expression pattern during
      embryogenesis was found to be conserved between SrGRAM and FIL from Arabidopsis.
      During subsequent seedling development SrGRAM expression in S. rexii was closely
      associated with the activity of the BM of the macrocotyledon and consecutively
      produced phyllomorphs, whereas it was excluded from the SAM-like meristem. Our
      results suggest that SrGRAM acts in intercalary growth and that an altered
      regulation of SrGRAM may underlay the evolution of the BM in S. rexii.

PMID- 20156284
TI  - The enigma of reversed asymmetry in lithodid crabs: absence of evidence for
      heritability or induction of morphological handedness in Lopholithodes
      foraminatus.
AB  - Mutations or environmental factors that result in reversal of conspicuous left
      right asymmetries provide an opportunity to study developmental mechanisms. They
      may also provide insight into evolutionary changes in asymmetry states within and
      between species. King crabs (family Lithodidae) have a larger right claw and
      females typically exhibit a dextrally offset abdomen. Nevertheless, I observed a
      high incidence of left handedness in laboratory reared box crabs (Lopholithodes
      foraminatus) and captured the first known egg-bearing female lithodid to exhibit
      reversed asymmetry. This provided a unique opportunity to characterize the
      reversed phenotype and to compare the incidence of reversed asymmetry in the
      offspring of normal and reversed females. Asymmetry of the chelae became apparent
      in the first postzoeal stage (glaucothoe) and handedness was maintained through
      subsequent instars. Females with larger left claws developed reversed abdominal
      asymmetry by the fourth crab stage. No reversed asymmetry was observed in the
      mandibles of zoea larvae or juveniles of either handedness. The incidence of
      reversed asymmetry in glaucothoe reared from one reversed and three normal
      females was high (between 20% and 30%), and independent of maternity (P=0.67).
      Removal of the right cheliped of fourth stage zoeae, and the major cheliped of
      glaucothoe, did not reverse the direction of asymmetry. Elevated larval rearing
      temperature also did not affect the frequency of reversed individuals. This lack
      of evidence for either heritability or induction of handedness is enigmatic.
      Further investigation of reversed asymmetry in lithodid crabs may provide
      valuable insights into the development and evolution of bilateral asymmetries.

PMID- 20156286
TI  - Altricial development in subsocial cockroach ancestors: foundation for the
      evolution of phenotypic plasticity in termites.
AB  - Basal termites possess two developmental features that eusocial Hymenoptera lack:
      the majority of colony members are juveniles whose somatic and reproductive
      development is temporarily or permanently suspended, and individual development
      is characterized by extreme phenotypic plasticity. An examination of the
      literature indicates that the basis for these unique ontogenetic characters is
      not the prolongation of a pronymphal stage into postembryonic development, as
      recently suggested. Like other hemimetabolous insects, termites have three
      embryonic cuticles, and the pronymphal (EC3) cuticle is shed during or shortly
      after hatch. Nonetheless, a different developmental landmark, dorsal closure,
      occurs later during embryogenesis in termites than it does in their cockroach
      relatives, clearly indicating ontogenetic repatterning from an ancestral state.
      An alternate hypothesis for the origin of isopteran phenotypic plasticity becomes
      apparent if we remain focused on the phylogenetic and social context of termite
      evolution. Altricial development occurs in both vertebrate and invertebrate taxa,
      evolves in response to the parental environment, and is displayed by two
      distantly related, biparental, wood-feeding cockroaches, including Cryptocercus,
      the sister-group to termites. It is therefore likely the condition was present in
      subsocial termite ancestors, and played a complex, multidimensional role in the
      transition to eusociality. Most relevant to current arguments is that a shift in
      responsibility for the care of altricial dependents, from parents to the first
      nutritionally independent nymphs in the family (alloparents), resulted in the
      developmental stasis of alloparents at a relatively young age. Because early
      instar cockroaches are not metamorphically competent, these young alloparents
      would have provided a novel developmental template on which selection could act.

PMID- 20156285
TI  - Phylogenetic analysis of developmental and postnatal mouse cell lineages.
AB  - Fate maps depict how cells relate together through past lineage relationships,
      and are useful tools for studying developmental and somatic processes. However,
      with existing technologies, it has not been possible to generate detailed fate
      maps of complex organisms such as the mouse. We and others have therefore
      proposed a novel approach, "phylogenetic fate mapping," where patterns of somatic
      mutation carried by the individual cells of an animal are used to retrospectively
      deduce lineage relationships through phylogenetic inference. Here, we have
      cataloged genomic polymorphisms at 324 mutation-prone polyguanine tracts for
      nearly 300 cells isolated from a single mouse, and have explored the cells'
      lineage relationships both phylogenetically and through a network-based approach.
      We present a model of mouse embryogenesis, where an early period of substantial
      cell mixing is followed by more coherent growth of clones later. We find that
      cells from certain tissues have greater numbers of close relatives in other
      specific tissues than expected from chance, suggesting that those populations
      arise from a similar pool of ancestral lineages. Finally, we have investigated
      the dynamics of cell turnover (the frequency of cell loss and replacement) in
      postnatal tissues. This work offers a longitudinal study of developmental
      lineages, from conception to adulthood, and provides insight into basic questions
      of mouse embryology as well as the somatic processes that occur after birth.

PMID- 20156289
TI  - Synthetic constrained peptide selectively binds and antagonizes death receptor 5.
AB  - Apoptosis or programmed cell death is an inherent part of the development and
      homeostasis of multicellular organisms. Dysregulation of apoptosis is implicated
      in the pathogenesis of diseases such as cancer, neurodegenerative diseases and
      autoimmune disorders. Tumour necrosis factor-related apoptosis-inducing ligand
      (TRAIL) is able to induce apoptosis by binding death receptor (DR)4 (TRAIL-R1)
      and DR5 (TRAIL-R2), which makes TRAIL an interesting and promising therapeutic
      target. To identify peptides that specifically interact with DR5, a disulfide
      constrained phage display peptide library was screened for binders towards this
      receptor. Phage-displayed peptides were identified that bind specifically to DR5
      and not to DR4, nor any of the decoy receptors. We show that the synthesized
      peptide, YCKVILTHRCY, in both monomeric and dimeric forms, binds specifically to
      DR5 in such a way that TRAIL binding to DR5 is inhibited. Surface plasmon
      resonance studies showed higher affinity towards DR5 for the dimeric form then
      the monomeric form of the peptide, with apparent K(d) values of 40 nm versus 272
      nm, respectively. Binding studied on cell lines by flow cytometry analyses showed
      concentration-dependent binding. Upon co-incubation with increasing
      concentrations of TRAIL, the peptide binding was reduced. Moreover, both the
      monomeric and dimeric forms of the peptide reduced TRAIL-induced cell death in
      Colo205 colon carcinoma cells. The peptide, YCKVILTHRCY, or its derivates, may be
      a useful investigative tool for dissecting signalling via DR5 relative to DR4 or
      could act as a lead peptide for the development of therapeutic agents in diseases
      with dysregulated TRAIL-signalling.

PMID- 20156290
TI  - Epidermal growth factor receptor gene numerical aberrations are frequent events
      in actinic keratoses and invasive cutaneous squamous cell carcinomas.
AB  - Epidermal growth factor receptor (EGFR) gene amplification and protein
      overexpression are common in several cancers. EGFR status has seldom been studied
      in cutaneous squamous carcinomas (SCCs), or their precursors, actinic keratoses
      (AKs). We evaluated the presence of EGFR genomic aberrations and EGFR protein
      overexpression in 25 AKs and 35 invasive SCCs by means of fluorescence in situ
      hybridization (FISH) and immunohistochemistry. EGFR numerical aberrations were
      detected in 52% of AKs and 77.1% of SCCs (P = 0.042). EGFR amplification was
      identified in 12% of AKs and 20% of SCCs. No differences regarding EGFR numerical
      aberrations were observed when AKs with high-grade dysplasia were compared with
      SCCs. A good correlation was observed between EGFR numerical aberrations and EGFR
      overexpression. Our results suggest that EGFR numerical aberrations occur in the
      early stages of epithelial carcinogenesis in skin, not playing a role in the
      progression from low-grade SCCs into more aggressive phenotypes.

PMID- 20156293
TI  - The evolution of water transport in plants: an integrated approach.
AB  - This review examines the evolution of the plant vascular system from its
      beginnings in the green algae to modern arborescent plants, highlighting the
      recent advances in developmental, organismal, geochemical and climatological
      research that have contributed to our understanding of the evolution of xylem.
      Hydraulic trade-offs in vascular structure-function are discussed in the context
      of canopy support and drought and freeze-thaw stress resistance. This qualitative
      and quantitative neontological approach to palaeobotany may be useful for
      interpreting the water-transport efficiencies and hydraulic limits in fossil
      plants. Large variations in atmospheric carbon dioxide levels are recorded in
      leaf stomatal densities, and may have had profound impacts on the water
      conservation strategies of ancient plants. A hypothesis that links vascular
      function with stomatal density is presented and examined in the context of the
      evolution of wood and/or vessels. A discussion of the broader impacts of plant
      transport on hydrology and climate concludes this review.

PMID- 20156294
TI  - Arsenic release and attenuation in low organic carbon aquifer sediments from West
      Bengal.
AB  - High arsenic concentrations in groundwater are causing a humanitarian disaster in
      Southeast Asia. It is generally accepted that microbial activities play a
      critical role in the mobilization of arsenic from the sediments, with metal
      reducing bacteria stimulated by organic carbon implicated. However, the detailed
      mechanisms underpinning these processes remain poorly understood. Of particular
      importance is the nature of the organic carbon driving the reduction of sorbed
      As(V) to the more mobile As(III), and the interplay between iron and sulphide
      minerals that can potentially immobilize both oxidation states of arsenic. Using
      a multidisciplinary approach, we identified the critical factors leading to
      arsenic release from West Bengal sediments. The results show that a cascade of
      redox processes was supported in the absence of high loadings of labile organic
      matter. Arsenic release was associated with As(V) and Fe(III) reduction, while
      the removal of arsenic was concomitant with sulphate reduction. The microbial
      populations potentially catalysing arsenic and sulphate reduction were identified
      by targeting the genes arrA and dsrB, and the total bacterial and archaeal
      communities by 16S rRNA gene analysis. Results suggest that very low
      concentrations of organic matter are able to support microbial arsenic
      mobilization via metal reduction, and subsequent arsenic mitigation through
      sulphate reduction. It may therefore be possible to enhance sulphate reduction
      through subtle manipulations to the carbon loading in such aquifers, to minimize
      the concentrations of arsenic in groundwaters.

PMID- 20156295
TI  - Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis
      B virus infection for the fiscal year 2008 in Japan.
AB  - In the 2008 guidelines for the treatment of patients with cirrhosis, who are
      infected with hepatitis B virus (HBV), the main goal is to normalize levels of
      alanine and aspartate aminotransferases by eliminating HBV or reducing viral
      loads. In patients with compensated cirrhosis, the clearance of HBV from serum is
      aimed for by entecavir, as the main resort, for histological improvement toward
      the prevention of hepatocellular carcinoma (HCC). In patients with decompensated
      cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the
      reversal to compensation, toward the eventual goal of decreasing the risk of HCC.
      For maintaining liver function and preventing HCC, branched chain amino acids and
      nutrient supplements are applied, in addition to conventional liver supportive
      therapies. For patients with chronic hepatitis B, separate guidelines are applied
      to those younger than 35 years and those aged 35 years or older. Even for
      patients with chronic hepatitis who are negative for hepatitis e antigen (HBeAg),
      but who harbor HBV DNA in titers of 7 log copies/mL or more, a "drug-free state"
      is aimed for by sequential treatment with interferon (IFN) plus entecavir as the
      first line. For patients with chronic hepatitis B aged 35 years or older, who are
      HBeAg-negative and carry HBV DNA in titers of less than 7 log copies/mL, long
      term IFN for 24-48 weeks is adopted anew. To HBeAg-negative patients who have
      either or both platelet counts of less than 150 x 10(3)/mm(3) and less than 7 log
      copies of HBV DNA, also, long-term IFN for 24-48 weeks is indicated.

PMID- 20156296
TI  - Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis
      C virus infection for the fiscal year 2008 in Japan.
AB  - In the 2008 guidelines for the treatment of patients with chronic hepatitis C,
      pegylated interferon (Peg-IFN) combined with ribavirin for 48 weeks are indicated
      for treatment-naive patients infected with hepatitis C virus (HCV) of genotype 1.
      Treatment is continued for an additional 24 weeks (72 weeks total) in the
      patients who have remained positive for HCV RNA detectable by the real-time
      polymerase chain reaction at 12 weeks after the start of treatment, but who turn
      negative for HCV RNA during 13-36 weeks on treatment. Re-treatment is aimed to
      either eradicate HCV or normalize transaminase levels for preventing the
      development of hepatocellular carcinoma (HCC). For patients with compensated
      cirrhosis, the clearance of HCV RNA is aimed toward improving histological
      damages and decreasing the development of HCC. The recommended therapeutic
      regimen is the initial daily dose of 6 million international units (MIU) IFN
      continued for 2-8 weeks that is extended to longer than 48 weeks, if possible.
      IFN dose is reduced to 3 MIU daily in patients who fail to clear HCV RNA by 12
      weeks for preventing the development of HCC. Splenectomy or embolization of the
      splenic artery is recommended to patients with platelet counts of less than 50 x
      103/mm(3) prior to the commencement of IFN treatment. When the prevention of HCC
      is at issue, not only IFN, but also liver supportive therapy such as stronger neo
      minophagen C, ursodeoxycholic acid, phlebotomy, branched chain amino acids
      (BCAA), either alone or in combination, are given. In patients with decompensated
      cirrhosis, by contrast, reversal to compensation is attempted.

PMID- 20156297
TI  - Geographical and genetic diversity of the human hepatitis B virus.
AB  - Hepatitis B virus (HBV) is one of the most widely distributed viruses that infect
      humankind. Distinct clinical and virological characteristics of the HBV-infection
      have been reported in different geographical parts of the world and are
      increasingly associated with genetic diversity of the infecting virus. HBV is
      classified into genotypes and subgenotypes that are associated with ethnicity and
      geography. The genetic diversity of HBV in its various aspects has been the
      subject of extensive investigations during the last few decades. Since molecular
      epidemiology research tools have become widely available, the number of new
      publications in this field has grown exponentially. This review summarises the
      recent publications on the geographical distribution of genetic variants of HBV,
      and proposes updated criteria for the identification of new genotypes and
      subgenotypes of the virus.

PMID- 20156298
TI  - Pregnancy and chronic hepatitis B virus infection.
AB  - The combination of chronic hepatitis B virus (HBV) infection and pregnancy
      presents unique management questions. Aspects of care that need to be considered
      include effects of hepatitis B on pregnancy, effects of pregnancy itself on the
      course of hepatitis B infection, treatment of hepatitis B during pregnancy and
      prevention of mother-to-infant transmission. Chronic HBV infection is usually
      mild in pregnant women, but may flare shortly after delivery. Effect of HBV
      infection on pregnancy outcomes are generally favorable, but may depend on
      severity of liver disease. Mother-to-infant transmission can be minimized by
      current immunoprophylaxis strategies, however, high levels of viremia in mothers
      may be a factor in the small but reproducible failure rate of current
      immunoprophylaxis strategies. Use of antivirals during pregnancy needs to be
      individualized. Careful planning and management of pregnancy must be done among
      patients with chronic HBV infection.

PMID- 20156299
TI  - Treatment of Primary Biliary Cirrhosis: A new challenge?
AB  - Primary biliary cirrhosis (PBC) is characterized by unknown etiologies, anti
      mitochondrial antibodies, injury of the biliary duct and the lack of a definite
      remedy. The etiologies of PBC have been well-discussed, including microorganisms
      and xenobiotics as the triggers for initiating the disease, and an abnormality of
      immune-tolerance. Recently, several animal models of PBC have been developed that
      may lead to the development of new therapies. Here, we reviewed the articles that
      address the etiology of PBC and the therapy for this disease for the confirmation
      of our current positions and future directions.

PMID- 20156300
TI  - Animal models for hepatitis C and related liver disease.
AB  - Persistent infection with hepatitis C virus (HCV) is a major risk toward
      development of hepatocellular carcinoma (HCC). The elucidation of pathogenesis of
      HCV-associated liver disease is hampered by the absence of appropriate animal
      models: there has been no animal model for HCV infection/pathogenesis except for
      the chimpanzee. In contrast, a number of transgenic mouse lines carrying the cDNA
      of the HCV genome have been established and evaluated in the study of HCV
      pathogenesis. The studies using transgenic mouse models, in which the HCV
      proteins such as the core protein are expressed, indicate the direct
      pathogenicity of HCV, including oncogenic activities. HCV transgenic mouse models
      also show a close relationship between HCV and some hepatic and extrahepatic
      manifestations such as hepatic steatosis, insulin resistance or Sjogren's
      syndrome. A crucial role of hepatic steatosis and insulin resistance in the
      pathogenesis of liver disease in HCV infection has been demonstrated, implying
      hepatitis C to be a metabolic disease. Besides the data connecting liver fibrosis
      progression and the disturbance in lipid and glucose metabolisms in hepatitis C
      patients, a series of evidence was found showing the association between these
      two conditions and HCV infection, chiefly using transgenic mouse carrying the HCV
      genome. Furthermore, the persistent activation of peroxisome proliferator
      activated receptor (PPAR)-alpha has recently been found, yielding dramatic
      changes in the lipid metabolism and oxidative stress overproduction in
      cooperation with the mitochondrial dysfunction. These results would provide a
      clue for further understanding of the role of lipid metabolism in pathogenesis of
      hepatitis C including liver injury and hepatocarcinogenesis.

PMID- 20156301
TI  - Combination of transarterial chemoembolization and percutaneous local ablation
      therapy for hepatocellular carcinoma.

PMID- 20156302
TI  - Sex difference in non-alcoholic fatty liver disease and non-alcoholic
      steatohepatitis.

PMID- 20156303
TI  - Fish model leads to new findings in liver disease.

PMID- 20156304
TI  - New TET2 gene mutations in patients with myeloproliferative neoplasms and
      splanchnic vein thrombosis.

PMID- 20156305
TI  - Clinical implications of clopidogrel non-response in cardiovascular patients: a
      systematic review and meta-analysis.
AB  - BSUMMARY BACKGROUND: Previous studies have shown an important risk of
      cardiovascular events in patients with clopidogrel biological non-response, and
      data have shown considerable, unexplored heterogeneity. OBJECTIVES: To evaluate
      the magnitude of cardiovascular risk associated with clopidogrel non-response and
      to explore heterogeneity. METHODS: This was a systematic review and meta-analysis
      of prospective studies of patients treated with clopidogrel for symptomatic
      atherothrombosis, evaluated by light transmission aggregometry with ADP and
      monitored prospectively for clinical ischemic events. RESULTS: Fifteen studies
      were included, totaling 3960 patients, of whom 25% were considered to be
      clopidogrel non-responders. The global relative risk (RR) for recurrent ischemic
      events in clopidogrel non-responders was 3.5 [95% confidence interval (CI) 2.4
      5.2, P < 0.0001]. The results of the different studies were heterogeneous
      (Cochran P = 0.01 and I(2) = 52%). The most recent studies yielded lower RRs
      [global RR = 2.9 (95% CI 2.3-3.8) after 2007, and global RR = 6.6 (95% CI 3.7
      11.9) before 2007, P = 0.01]. Heterogeneity was present in the group of studies
      in which more than 10% of patients took glycoprotein (GP)IIb-IIIa inhibitors
      [Cochran P = 0.003 and I(2) = 70%; RR = 3.8 (95% CI 2.9-5.1)] and was absent in
      the other studies [Cochran P = 0.88 and I(2) = 0; RR = 2.5 (95% CI 1.7-3.6)]. The
      RR was significantly higher in studies using higher ADP maximal aggregation cut
      offs (> 65%) for clopidogrel non-response than in studies using lower cut-offs
      [RR = 5.8 (95% CI 3.2-10.3) and RR = 2.9 (95% CI 2.2-3.7), respectively, P =
      0.03]. CONCLUSIONS: The risk of ischemic events associated with clopidogrel non
      response is now more precisely defined. The risk is heterogeneous across studies,
      possibly because of an interaction with GPIIb-IIIa inhibitors and the use of
      different cut-offs to identify non-responders.

PMID- 20156306
TI  - HPLC purification and re-evaluation of chemical identity of two circular
      bacteriocins, gassericin A and reutericin 6.
AB  - AIM: The study aimed for the complete purification and recharacterization of the
      highly hydrophobic circular bacteriocins, gassericin A and reutericin 6. METHODS
      AND RESULTS: Gassericin A and reutericin 6 were purified to homogeneity using
      previously described method and reverse-phase HPLC with an octyl column and
      eluents of aqueous acetonitrile and 2-propanol. Mass analysis, N-terminal
      sequencing and bacteriocin assay of the HPLC-purified bacteriocins showed the two
      bacteriocins had identical seamless circular structures with the same m/z value
      (5651) of [M + H](+) and both had the same specific activity. D/L-amino acid
      composition analysis using two distinct methods with the chiral fluorescent
      derivatization reagents (+)-1-(9-fluorenyl)ethyl chloroformate and O
      phthalaldehyde/N-acetyl-L-cystein revealed neither gassericin A nor reutericin 6
      contained D-alanine residues contrary to our previous results. CONCLUSION:
      Purified gassericin A and reutericin 6 are chemically identical circular
      molecules containing no D-alanine residues. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The HPLC conditions developed in this study will facilitate advanced purification
      and correct characterization of other highly hydrophobic bacteriocins.

PMID- 20156307
TI  - Notes on the almost unknown genus Jeotgalicoccus.
AB  - AIMS: To facilitate isolation and differentiation of the almost entirely unknown
      Jeotgalicoccus spp. METHODS AND RESULTS: Jeotgalicoccus spp. have been found in
      dust samples using SSCP-PCR analysis. As the cultivation of strains is necessary
      for further studies on virulence, pathogenicity or metabolism, we developed a
      method for cultural isolation and further differentiation of Jeotgalicoccus spp.
      We found that J. halotolerans, J. psychrophilus, J. marinus, as well as the
      related species Salinicoccus roseus grow on Baird Parker (BP) agar as black
      colonies without clear zones. J. pinnipedialis and S. jeotgali grow only weakly
      on BP agar without forming clearly delineated colonies. On BP agar, the colony
      forming Jeotgalicoccus and Salinicoccus spp. are not distinguishable from
      coagulase-negative Staphylococcus spp. (CNS). However, unlike CNS, all of the
      above mentioned species are unreactive in the OF test. SSCP-PCR was able to
      differentiate between all investigated Jeotgalicoccus and Salinicoccus spp., as
      all species had different band positions. CONCLUSIONS: Jeotgalicoccus spp. and
      Salinicoccus spp. may be widely distributed in the environment, but, until now,
      overlooked or confused with staphylococci. Further epidemiological studies, which
      are required to prove this hypothesis, are facilitated by the observations of our
      study. SIGNIFICANCE AND IMPACT: This not yet published information enables
      researchers to carry out epidemiological studies on Jeotgalicoccus spp. in a very
      cheap and easy way.

PMID- 20156308
TI  - Screening and characterization of butanol-tolerant micro-organisms.
AB  - AIMS: Poor butanol tolerance of solventogenic stains directly limits their
      butanol production during industrial-scale fermentation process. This study was
      performed to search for micro-organisms possessing elevated tolerance to butanol.
      METHODS AND RESULTS: Two strains, which displayed higher butanol tolerance
      compared to commonly used solventogenic Clostridium acetobutylicum, were isolated
      by evolution and screening strategies. Both strains were identified as lactic
      acid bacteria (LAB). On this basis, a LAB culture collection was tested for
      butanol tolerance, and 60% of the strains could grow at a butanol concentration
      of 2.5% (v/v). In addition, an isolated strain with superior butanol tolerance
      was transformed using a certain plasmid. CONCLUSIONS: The results indicate that
      many strains of LAB possessed inherent tolerance of butanol. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study suggests that LAB strains may be capable of
      producing butanol to elevated levels following suitable genetic manipulation.

PMID- 20156309
TI  - Secondary metabolites produced by a root-inhabiting sterile fungus antagonistic
      towards pathogenic fungi.
AB  - AIMS: A sterile red fungus (SRF) isolated from cortices of roots of both wheat
      (Triticum aestivum cv. Gamenya) and ryegrass (Lolium rigidum cv. Wimmera) was
      found to protect the hosts from phytopathogens and promote plant growth. In this
      work, the major secondary metabolites produced by this SRF were analysed, and
      their antibiotic and plant-growth-promoting activities investigated. METHODS AND
      RESULTS: Two main compounds, veratryl alcohol (VA) and 4-(hydroxymethyl)
      quinoline, were isolated from the culture filtrate of the fungus. In antifungal
      assays, VA inhibited the growth of Sclerotinia sclerotiorum and Pythium
      irregulare even at low amounts, while high concentrations (>100 microg per plug)
      of 4-(hydroxymethyl)-quinoline were needed. Both metabolites revealed weak
      inhibition of Rhizoctonia solani. Furthermore, both compounds showed a growth
      promotion activity on canola (Brassica napus) seedlings used as bioassays.
      CONCLUSIONS: Isolation and characterization of the main secondary metabolites
      from culture filtrates of a root-inhabiting sterile fungus are reported. The
      biological assays indicate that these secondary metabolites may have a role in
      both plant growth regulation and antifungal activity. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This study provides a better understanding of the metabolism of a
      cortical fungus that may have a useful role in the biological suppression of root
      infecting soil-borne plant pathogens.

PMID- 20156310
TI  - Anorectal function in patients with collagenous colitis in active and clinically
      quiescent phase, in comparison with healthy controls.
AB  - BACKGROUND: Collagenous colitis (CC) is characterized by chronic watery diarrhea,
      a macroscopically normal colonic mucosa but typical microscopic inflammation.
      Chronic mucosal inflammation of the colon and rectum has earlier been associated
      with altered visceral sensitivity, but anorectal function has never been reported
      in cases of CC. METHODS: Fifteen patients with CC in active phase recorded their
      symptoms. The severity of inflammation was determined in mucosal biopsies.
      Anorectal function was assessed and compared with that of 15 healthy volunteers
      of corresponding age and matched for gender. After 6 weeks of budesonide
      treatment when the patients were in clinical remission anorectal function was re
      assessed. KEY RESULTS: All patients had inflammation also in rectum. Patients in
      active phase had, during rectal balloon distension a higher rectal sensory
      threshold for the feeling of first sensation, compared with controls (P = 0.02).
      There were no differences in rectal sensory threshold for the feeling of urgency
      or maximum distension, between patients with CC in active phase and healthy
      controls. Rectal volume at first sensation was significantly greater in patients
      than in controls (P = 0.02), but there were no differences at urgency or maximum
      distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and
      all went into clinical remission. No differences in anorectal function were
      measured when patients had active disease, compared with clinical remission.
      CONCLUSIONS & INFERENCES: Collagenous colitis was not associated with rectal
      hypersensitivity or disturbed anal function despite rectal inflammation. On the
      contrary, the sensation threshold for light rectal pressure was elevated in
      patients with active CC.

PMID- 20156311
TI  - Splendors and miseries of expired CO2 measurement in the suspicion of pulmonary
      embolism.
AB  - Capnography has been studied for decades as a potential diagnostic tool for
      suspected pulmonary embolism. Despite technological refinements and its
      combination with other non-invasive instruments, no evidence to date allows
      recommending the use of expired carbon dioxide measurement as a rule-out test for
      pulmonary embolism without additional radiological testing. Further
      investigations are, however, still warranted.

PMID- 20156312
TI  - Complications of continuous renal replacement therapy in children: are all
      created equal?
AB  - Continuous renal replacement therapy (CRRT) in pediatric acute kidney dysfunction
      has evolved in recent decades; however, little objective data exist for
      complications associated with CRRT. Santiago and colleagues are among the first
      to document four complications of acute kidney dysfunction in critically ill
      children: catheterization-related insertion complications, hypotension,
      hemorrhage, and electrolyte disturbances. They reported that hypotension at
      connection (41.3%) and electrolyte disturbance (50.6%) were the leading
      complications. Although this study is limited by small sample size and the
      outcome variables measured, it is an important first step in assessing outcomes
      of CRRT in children. A prospective multicenter randomized trial will be needed to
      fully delineate the complications and define the risk/benefit ratio of CRRT in
      children.

PMID- 20156313
TI  - Tracheostomy patients on the ward: multiple benefits from a multidisciplinary
      team?
AB  - Patients requiring tracheostomies tend to have a longer length of stay due to
      their underlying disease. After a thorough literature search, Garrubba and
      colleagues found only three studies assessing the impact of multidisciplinary
      teams (MDTs) on tracheostomy patients on the ward. One consistent observation was
      the decreased time to decannulation after institution of MDT care when compared
      with historical controls. Although a large prospective randomized trial is
      desirable before MDT is recommended, many institutions may have already formed a
      team approach to provide coordinated care resulting in improved outcome and
      length of stay.

PMID- 20156314
TI  - Rising in the East.

PMID- 20156315
TI  - Figuring out what works: a need for more and better studies on the relationship
      between ICU organization and outcomes.
AB  - Modifying how intensive care units (ICUs) are organized and run offers major
      opportunities to improve outcomes. In the previous issue of Critical Care,
      Billington and colleagues assessed the association of outcomes with intensivists'
      base speciality. However, very little is known about the relationships between
      ICU organization and outcomes. In the systems-based paradigm of quality
      improvement, every aspect of what we do and how we do it is a candidate for study
      and change. While we need much more rigorous research assessing every aspect of
      this large question, there are substantial barriers to conducting such studies.

PMID- 20156317
TI  - Downstream EWS/FLI1 - upstream Ewing's sarcoma.
AB  - Ewing's sarcoma family tumors are a good example of how genome research has
      advanced our understanding of the molecular pathogenesis of an otherwise
      enigmatic disease. This group of embryonal bone tumors is characterized by the
      expression of a chimeric ETS-family oncogene, predominantly EWS/FLI1. There is
      now convincing evidence for a mesenchymal descent from an early pluripotent
      progenitor. EWS/FLI1 has been shown to drive proliferation of Ewing's sarcoma
      cells and block most of the differentiation potential except for a partial neural
      gene expression program. The EWS/FLI1 fusion protein acts mainly as a gene
      activator, directly interacting with chromatin at two kinds of binding site:
      distant enhancers enriched in GGAA microsatellites, and proximal promoters
      containing classical ETS-binding motifs and recognition motifs for other
      transcription factors. EWS/FLI1 also represses a large number of genes, mainly
      indirectly, presumably by altering microRNA expression and epigenetic mechanisms,
      and potentially affecting post-transcriptional gene regulation. Modulation of
      EWS/FLI1 expression is not only a desirable therapeutic goal, but may also occur
      under physiological conditions and influence the course of the disease.

PMID- 20156316
TI  - Clinical review: Fresh frozen plasma in massive bleedings - more questions than
      answers.
AB  - Fresh frozen plasma (FFP) is indicated for the management of massive bleedings.
      Recent audits suggest physician knowledge of FFP is inadequate and half of the
      FFP transfused in critical care is inappropriate. Trauma is among the largest
      consumers of FFP. Current trauma resuscitation guidelines recommend FFP to
      correct coagulopathy only after diagnosed by laboratory tests, often when overt
      dilutional coagulopathy already exists. The evidence supporting these guidelines
      is limited and bleeding remains a major cause of trauma-related death. Recent
      studies demonstrated that coagulopathy occurs early in trauma. A novel early
      formula-driven haemostatic resuscitation proposes addressing coagulopathy early
      in massive bleedings with FFP at a near 1:1 ratio with red blood cells. Recent
      retrospective reports suggest such strategy significantly reduces mortality, and
      its use is gradually expanding to nontraumatic bleedings in critical care. The
      supporting studies, however, have bias limiting the interpretation of the
      results. Furthermore, logistical considerations including need for immediately
      available universal donor AB plasma, short life after thawing, potential waste
      and transfusion-associated complications have challenged its implementation. The
      present review focuses on FFP transfusion in massive bleeding and critically
      appraises the evidence on formula-driven resuscitation, providing resources to
      allow clinicians to develop informed opinion, given the current deficient and
      conflicting evidence.

PMID- 20156318
TI  - When rheumatology meets hepatology: are anti-TNFs safe in hepatitis B virus
      carriers?
AB  - Over the past decades, more effective and less toxic biologicals have
      revolutionized rheumatology therapy in our battle against the autoimmune chronic
      inflammation of rheumatoid arthritis and spondyloarthropathy. But what about for
      patients who have previously had an infection of the liver? Prior hepatitis B
      virus infection clearly presents a challenge for clinicians. In a study by
      Charpin and colleagues of 21 patients whose hepatitis B virus serology suggested
      carrier status, anti-TNF treatment appeared to be safe during a limited follow-up
      period of 3 years. Studies are needed with longer follow-up, particularly in
      patients with low antibody titres (antiHBc). In the 3-year period, however, about
      30% of the patients developed significant lowering of antibody titres, which may
      become relevant during long-term follow-up. Charpin and colleagues are the first
      to reveal promising data on the relative safety of anti-TNFs in a small series of
      hepatitis B carriers for up to 3 years.

PMID- 20156319
TI  - From the item to the outcome: the promising prospects of PROMIS.
AB  - Evaluation of patient reported outcomes, and in particular physical function,
      have gained increasing importance in research and therapy of patients with
      rheumatic diseases. Most instruments that are used for that purpose are rigid and
      suffer from floor and ceiling effects when used in patients whose physical
      function differs from the average. A new approach to the assessment of physical
      function uses computerised adaptive testing, by which precision and reliability
      of the measurement can be achieved for most patients, while even requiring less
      time for the assessment. Well calibrated and tested item and large item data
      banks are a prerequisite for this purpose, a process that is summarised in the
      present report by Bruce and colleagues.

PMID- 20156320
TI  - Tracking the genomic evolution of breast cancer metastasis.
AB  - Therapeutic choices for metastatic tumors are, in most cases, based upon the
      histological and molecular analysis of the corresponding primary tumor.
      Understanding whether and to what extent the genomic landscape of metastasis
      differs from the tumors from which they originated is critical yet largely
      unknown. A recent report tackled this key issue by comparing the genomic and
      transcriptional profile of a metastatic lobular breast tumor with that of the
      primary tumor surgically removed 9 years earlier. The extent of the differences
      suggests a high degree of mutational heterogeneity between primary and metastatic
      lesions and indicates that significant evolution occurs during breast cancer
      progression.

PMID- 20156321
TI  - Reprogramming of the non-coding transcriptome during brain development.
AB  - A recent global analysis of gene expression during the differentiation of
      neuronal stem cells to neurons and oligodendrocytes indicates a complex pattern
      of changes in the expression of both protein-coding transcripts and long non
      protein-coding RNAs.

PMID- 20156322
TI  - Value and price of ventilator-associated pneumonia surveillance as a quality
      indicator.

PMID- 20156323
TI  - Prophylactic open abdomen in patients with postoperative intra-abdominal
      hypertension.
AB  - Postoperative intra-abdominal hypertension (IAH) is a frequent occurrence in
      critically ill patients operated on for severe abdominal trauma, secondary
      peritonitis or ruptured abdominal aortic aneurysm. IAH may progress to abdominal
      compartment syndrome (ACS) with new-onset organ dysfunction. Early recognition of
      IAH and interventions that prevent the development of ACS may preserve vital
      organ functions and increase the probability of survival. The best method to
      prevent postoperative ACS is to leave the abdomen open during the operation. The
      decision to leave the abdomen open is usually based on the surgeon's judgment
      without intra-abdominal pressure (IAP) measurements during the operation. Because
      significant morbidity and mortality are associated with the open abdomen, the
      measurement of IAP immediately after the fascial closure, when feasible, could
      offer an objective method for determining the optimal IAP threshold for leaving
      the abdomen open. The management of the open abdomen requires a temporary
      abdominal closure (TAC) system that would ideally prevent the development of ACS
      and facilitate later primary fascia closure. Among several TAC systems, the most
      promising are those that provide negative pressure to the wound or continuous
      fascial traction or both.

PMID- 20156325
TI  - A role for age-related changes in TGFbeta signaling in aberrant chondrocyte
      differentiation and osteoarthritis.
AB  - Transforming growth factor beta (TGFbeta) is a growth factor with many faces. In
      our osteoarthritis (OA) research we have found that TGFbeta can be protective as
      well as deleterious for articular cartilage. We postulate that the dual effects
      of TGFbeta on chondrocytes can be explained by the fact that TGFbeta can signal
      via different receptors and related Smad signaling routes. On chondrocytes,
      TGFbeta not only signals via the canonical type I receptor ALK5 but also via the
      ALK1 receptor. Notably, signaling via ALK5 (Smad2/3 route) results in markedly
      different chondrocyte responses than ALK1 signaling (Smad1/5/8), and we postulate
      that the balance between ALK5 and ALK1 expression on chondrocytes will determine
      the overall effect of TGFbeta on these cells. Importantly, signaling via ALK1,
      but not ALK5, stimulates MMP-13 expression by chondrocytes. In cartilage of
      ageing mice and in experimental OA models we have found that the ALK1/ALK5 ratio
      is significantly increased, favoring TGFbeta signaling via the Smad1/5/8 route,
      changes in chondrocyte differentiation and MMP-13 expression. Moreover, human OA
      cartilage showed a significant correlation between ALK1 and MMP-13 expression. In
      this paper we summarize concepts in OA, its link with ageing and disturbed growth
      factor responses, and a potential role of TGFbeta signaling in OA development.

PMID- 20156326
TI  - Regulation of metabolism in Caenorhabditis elegans longevity.
AB  - The nematode Caenorhabditis elegans is a favorite model for the study of aging. A
      wealth of genetic and genomic studies show that metabolic regulation is a
      hallmark of life-span modulation. A recent study in BMC Biology identifying
      metabolic signatures for longevity suggests that amino-acid pools may be
      important in longevity.

PMID- 20156327
TI  - Have the roles of two functional polymorphisms in breast cancer, R72P in P53 and
      MDM2-309 in MDM2, become clearer?
AB  - Genetic differences between individuals have been predicted to account for
      disparate outcomes in patients diagnosed with cancer. The search for genetic
      determinants has been ongoing for a considerable amount of time and it is only
      now that insights have been gained into which polymorphisms are most likely to be
      important in determining not only disease likelihood but also outcome. The quest
      to be able to accurately predict patient outcomes in breast cancer may now be a
      step closer as increased sample size is leading to more robust statistical
      analysis and a better understanding of molecular mechanisms of disease are
      forthcoming.

PMID- 20156328
TI  - Bunched and Madm: a novel growth-regulatory complex?
AB  - By combining Drosophila genetics and proteomics Gluderer et al. report in this
      issue of Journal of Biology the isolation of a novel growth-regulatory complex
      consisting of Bunched and Madm. Future study of this complex will address the
      precise mechanism of growth control, regulation of complex activity, the
      interface with other growth pathways and a potential role in human cancer.

PMID- 20156329
TI  - Hourly measurements not required for safe and effective glycemic control in the
      critically ill patient.

PMID- 20156330
TI  - Early vs late start of dialysis: it's all about timing.
AB  - Acute kidney injury (AKI) is now well recognized as an independent risk factor
      for increased morbidity and mortality, particularly when dialysis is needed. The
      wide variation in dialysis utilization contributes to a lack of consensus on what
      parameters should guide the decision to start dialysis. While the association of
      early initiation of dialysis with survival benefit was first demonstrated four
      decades ago, few studies in the modern era of dialysis have addressed time of
      dialysis initiation. Though listed as one of the top priorities in research on
      AKI, timing of dialysis initiation has not been included as a factor in any of
      the large, randomized controlled trials in this area.

PMID- 20156331
TI  - Determining relevant cortisol concentrations in critically ill patients.
AB  - The importance of adrenal function to survival in critically ill patients has
      been established; however, identifying the best method to diagnose adrenal
      insufficiency has been problematic. Multiple methods of determining adrenal
      function have been developed, each with its advantages and disadvantages. Serum
      free cortisol levels are probably the most accurate, although obtaining this
      result is technically demanding. Cohen and colleagues investigated the
      feasibility of measuring tissue cortisol levels in burn patients and whether
      tissue cortisol levels could be used as a surrogate for plasma-free cortisol
      levels.

PMID- 20156332
TI  - Inversion variants in the human genome: role in disease and genome architecture.
AB  - Significant advances have been made over the past 5 years in mapping and
      characterizing structural variation in the human genome. Despite this progress,
      our understanding of inversion variants is still very restricted. While
      unbalanced variants such as copy number variations can be mapped using array
      based approaches, strategies for characterization of inversion variants have been
      limited and underdeveloped. Traditional cytogenetic approaches have long been
      able to identify microscopic inversion events, but discovery of submicroscopic
      events has remained elusive and largely ignored. With the advent of paired-end
      sequencing approaches, it is now possible to map inversions across the human
      genome. Based on the paired-end sequencing studies published to date, it is now
      feasible to make a first map of inversions across the human genome and to use
      this map to explore the characteristics and distribution of this form of
      variation. The current map of inversions indicates that many remain to be
      identified, especially in the smaller size ranges. This review provides an
      overview of the current knowledge about human inversions and their contribution
      to human phenotypes. Further characterization of inversions should be considered
      as an important step towards a deeper understanding of human variation and genome
      dynamics.

PMID- 20156333
TI  - Estrogen receptor action in three dimensions - looping the loop.
AB  - Due to advances in genomic technologies, our understanding of estrogen receptor
      (ER)-mediated transcription in breast cancer cells has evolved significantly in
      recent years. Genome-wide mapping experiments revealed thousands of ER-binding
      events, but linking them to the target genes has been an ongoing struggle. A
      recent paper describes a new technique, called ChIA-PET (chromatin interaction
      analysis using paired-end tag sequencing), that can directly address these
      questions. ChIA-PET is an unbiased approach for simultaneously identifying all
      genome-wide binding events of a transcription factor and those involved in long
      range chromatin loops.

PMID- 20156334
TI  - Is Phytalgic(R) a goldmine for osteoarthritis patients or is there something
      fishy about this nutraceutical? A summary of findings and risk-of-bias
      assessment.
AB  - A food supplement containing fish oils, urtica dioica, zinc, and vitamin E
      (Phytalgic) for osteoarthritis (OA) has now been tested in a placebo-controlled
      trial for 3 months and according to the authors has a very large clinical effect,
      considerably larger than that of any other known product. Even experts endorsing
      nutraceuticals for OA symptoms would probably agree that a nutraceutical with an
      effect size above 0.5 is rarely seen. Despite our concerns about the fact that
      trial registration took place after the study was completed and the likelihood
      that patients would note the taste of fish, a circumstance that would lead to
      detection bias, we consider these data promising though with a high risk of bias.

PMID- 20156335
TI  - Diseases of the salivary glands in infants and adolescents.
AB  - BACKGROUND: Diseases of the salivary glands are rare in infants and children
      (with the exception of diseases such as parotitis epidemica and cytomegaly) and
      the therapeutic regimen differs from that in adults. It is therefore all the more
      important to gain exact and extensive insight into general and special aspects of
      pathological changes of the salivary glands in these age groups. Etiology and
      pathogenesis of these entities is still not yet fully known for the age group in
      question so that general rules for treatment, based on clinical experience,
      cannot be given, particularly in view of the small number of cases of the
      different diseases. Swellings of the salivary glands may be caused by acute and
      chronic inflammatory processes, by autoimmune diseases, by duct translocation due
      to sialolithiasis, and by tumors of varying dignity. Clinical examination and
      diagnosis has also to differentiate between salivary gland cysts and inflammation
      or tumors. CONCLUSION: Salivary gland diseases are rare in childhood and
      adolescence. Their pattern of incidence differs very much from that of adults.
      Acute and chronic sialadenitis not responding to conservative treatment requires
      an appropriate surgical approach. The rareness of salivary gland tumors is
      particularly true for the malignant parotid tumors which are more frequent in
      juvenile patients, a fact that has to be considered in diagnosis and therapy.

PMID- 20156336
TI  - Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in
      the serum of colorectal cancer patients: implications for early screening and
      detection.
AB  - BACKGROUND: There are currently no accurate serum markers for detecting early
      risk of colorectal cancer (CRC). We therefore developed a non-targeted
      metabolomics technology to analyse the serum of pre-treatment CRC patients in
      order to discover putative metabolic markers associated with CRC. Using tandem
      mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility
      of selected markers and this technology for discriminating between CRC and
      healthy subjects. METHODS: Biomarker discovery was performed using Fourier
      transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive
      metabolic profiles of CRC patients and controls from three independent
      populations from different continents (USA and Japan; total n = 222) were
      obtained and the best inter-study biomarkers determined. The structural
      characterization of these and related markers was performed using liquid
      chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical
      utility evaluations were performed using a targeted high-throughput triple
      quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in
      two further independent populations from the USA and Japan (total n = 220).
      RESULTS: Comprehensive metabolomic analyses revealed significantly reduced levels
      of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty
      acids in all three independent cohorts of CRC patient samples relative to
      controls. Structure elucidation studies on the C28 molecules revealed two
      families harbouring specifically two or three hydroxyl substitutions and varying
      degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS
      results in two further independent studies. In total, biomarkers in five
      independent populations across two continental regions were evaluated (three
      populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator
      characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 +/- 0.04).
      CONCLUSIONS: A novel comprehensive metabolomics technology was used to identify a
      systemic metabolic dysregulation comprising previously unknown hydroxylated
      polyunsaturated ultra-long chain fatty acid metabolites in CRC patients. These
      metabolites are easily measurable in serum and a decrease in their concentration
      appears to be highly sensitive and specific for the presence of CRC, regardless
      of ethnic or geographic background. The measurement of these metabolites may
      represent an additional tool for the early detection and screening of CRC.

PMID- 20156337
TI  - The role of glucocorticoid receptor phosphorylation in Mcl-1 and NOXA gene
      expression.
AB  - BACKGROUND: The cyclin-dependent kinase (CDK) and mitogen-activated protein
      kinase (MAPK) mediated phosphorylation of glucocorticoid receptor (GR) exerts
      opposite effects on GR transcriptional activity and affects other
      posttranslational modifications within this protein. The major phosphorylation
      site of human GR targeted by MAPK family is the serine 226 and multiple kinase
      complexes phosphorylate receptor at the serine 211 residue. We hypothesize that
      GR posttranslational modifications are involved in the determination of the
      cellular fate in human lymphoblastic leukemia cells. We investigated whether UV
      signalling through alternative GR phosphorylation determined the cell type
      specificity of glucocorticoids (GCs) mediated apoptosis. RESULTS: We have
      identified putative Glucocorticoid Response Elements (GREs) within the promoter
      regulatory regions of the Bcl-2 family members NOXA and Mcl-1 indicating that
      they are direct GR transcriptional targets. These genes were differentially
      regulated in CEM-C7-14, CEM-C1-15 and A549 cells by glucocorticoids and JNK
      pathway. In addition, our results revealed that the S211 phosphorylation was
      dominant in CEM-C7-14, whereas the opposite was the case in CEM-C1-15 where
      prevalence of S226 GR phosphorylation was observed. Furthermore, multiple GR
      isoforms with cell line specific patterns were identified in CEM-C7-14 cells
      compared to CEM-C1-15 and A549 cell lines with the same antibodies. CONCLUSIONS:
      GR phosphorylation status kinetics, and site specificity as well as isoform
      variability differ in CEM-C7-14, CEM-C1-15, and A549 cells. The positive or
      negative response to GCs induced apoptosis in these cell lines is a consequence
      of the variable equilibrium of NOXA and Mcl-1 gene expression potentially
      mediated by alternatively phosphorylated GR, as well as the balance of MAPK/CDK
      pathways controlling GR phosphorylation pattern. Our results provide molecular
      base and valuable knowledge for improving the GC based therapies of leukaemia.

PMID- 20156338
TI  - Survey of HBsAg-positive pregnant women and their infants regarding measures to
      prevent maternal-infantile transmission.
AB  - BACKGROUND: Intrauterine infection is the main contributor to maternal-infantile
      transmission of HBV. This is a retrospective study of 158 HBsAg-positive pregnant
      women who delivered children from Jan 1st, 2004 to Dec.31th, 2006 in Wuhan City,
      China. We investigated the measures taken to prevent maternal-infantile
      transmission of hepatitis B virus and the infection status of children. METHODS:
      HBsAg-positive pregnant women were selected by a random sampling method when they
      accepted prenatal care in district-level Maternal and Child Health Hospitals. On
      a voluntary basis, these women completed questionnaires by face-to-face or phone
      interviews. The collected data were used to evaluate the immunization programs
      that pregnant women had received for preventing hepatitis B maternal-infantile
      transmission. RESULTS: Among the 158 women, 143(90.5%) received Hepatitis B
      immune globulin during pregnancy, and 86.0% of their children were given
      Hepatitis B immune globulin and Hepatitis B vaccine. The rate of cesarean section
      was 82.3%, and 28.5% of these were aimed at preventing HBV infection. The rate of
      bottle feeding was 51.9%, and 89.0% of bottle feeding cases were for the purpose
      of preventing HBV infection. There were 71 cases of participants who were HBeAg
      positive. Compared with the HBsAg+ HBeAg- group (only HBsAg-positive), the HBsAg
      + HBeAg+ group (HBsAg-positive and HBeAg-positive) had significantly higher rates
      of the caesarean section and bottle feeding resulting from hepatitis B (P <
      0.05). Five cases were HBsAg-positive by Umbilical Cord Blood detection. The
      intrauterine infection rate of newborns was 6.7%. The chronic HBV rate of
      children was 4.0%. CONCLUSION: Most HBsAg positive pregnant women have a growing
      awareness of maternal-infantile transmission of Hepatitis B virus and are
      receiving some form of preventative treatment, like combined immunization.
      Caesarean and bottle feeding are very common, often primarily to prevent
      transmission. Relatively few intrauterine infections were identified in this
      sample, but many infants did not appear to seroconvert after vaccination.

PMID- 20156339
TI  - A tailored lifestyle intervention to reduce the cardiovascular disease risk of
      individuals with Familial Hypercholesterolemia (FH): design of the PRO-FIT
      randomised controlled trial.
AB  - BACKGROUND: Because of a high cardiovascular disease (CVD) risk in people with
      Familial Hypercholesterolemia (FH), early prevention of cardiovascular disease is
      important for health gain and cost reduction. This project focuses on the
      development and evaluation of an innovative intervention aiming to reduce CVD
      risk by promoting a healthy lifestyle among people with FH. METHODS: This project
      is designed as a randomised controlled trial in which individuals with FH will be
      assigned randomly to a control or intervention group. In the intervention group
      (n = 200), participants will receive a personalized intervention which is a
      combination of web-based tailored lifestyle advice and personal counselling by a
      lifestyle coach. The control group (n = 200) will receive care as usual. Primary
      outcomes are biological indicators of CVD risk: systolic blood pressure, glucose,
      BMI, waist circumference and lipids (triglycerides, total, LDL and HDL
      cholesterol). Secondary outcomes are: healthy lifestyle behaviour (with regard to
      smoking, physical activity, dietary pattern and compliance to statin therapy) and
      psychological correlates and determinants of healthy lifestyle behaviour
      (knowledge, attitude, risk perception, social influence, self-efficacy, cues to
      action, intention and autonomy). Measurement will take place at baseline, and at
      3 and 12 months after randomisation. Additionally, a throughout process
      evaluation will be conducted to assess and monitor intervention implementation
      during the trial. DISCUSSION: Results of the PRO-FIT project will provide
      information about the effects and implementation of a healthy lifestyle
      intervention for individuals with FH. Our experiences with this intervention will
      be indicative about the suitability, feasibility and benefits of this approach
      for future interventions in other high-risk groups, such as Familial Combined
      Hypercholesterolemia (FCH) and diabetes. TRIAL REGISTRATION NUMBER: NTR1899.

PMID- 20156340
TI  - A fuzzy gene expression-based computational approach improves breast cancer
      prognostication.
AB  - Early gene expression studies classified breast tumors into at least three
      clinically relevant subtypes. Although most current gene signatures are
      prognostic for estrogen receptor (ER) positive/human epidermal growth factor
      receptor 2 (HER2) negative breast cancers, few are informative for ER
      negative/HER2 negative and HER2 positive subtypes. Here we present Gene
      Expression Prognostic Index Using Subtypes (GENIUS), a fuzzy approach for
      prognostication that takes into account the molecular heterogeneity of breast
      cancer. In systematic evaluations, GENIUS significantly outperformed current gene
      signatures and clinical indices in the global population of patients.

PMID- 20156341
TI  - Analysis of a normalised expressed sequence tag (EST) library from a key
      pollinator, the bumblebee Bombus terrestris.
AB  - BACKGROUND: The bumblebee, Bombus terrestris (Order Hymenoptera), is of
      widespread importance. This species is extensively used for commercial
      pollination in Europe, and along with other Bombus spp. is a key member of
      natural pollinator assemblages. Furthermore, the species is studied in a wide
      variety of biological fields. The objective of this project was to create a B.
      terrestris EST resource that will prove to be valuable in obtaining a deeper
      understanding of this significant social insect. RESULTS: A normalised cDNA
      library was constructed from the thorax and abdomen of B. terrestris workers in
      order to enhance the discovery of rare genes. A total of 29'428 ESTs were
      sequenced. Subsequent clustering resulted in 13'333 unique sequences. Of these,
      58.8 percent had significant similarities to known proteins, with 54.5 percent
      having a "best-hit" to existing Hymenoptera sequences. Comparisons with the
      honeybee and other insects allowed the identification of potential candidates for
      gene loss, pseudogene evolution, and possible incomplete annotation in the
      honeybee genome. Further, given the focus of much basic research and the
      perceived threat of disease to natural and commercial populations, the immune
      system of bumblebees is a particularly relevant component. Although the library
      is derived from unchallenged bees, we still uncover transcription of a number of
      immune genes spanning the principally described insect immune pathways.
      Additionally, the EST library provides a resource for the discovery of genetic
      markers that can be used in population level studies. Indeed, initial screens
      identified 589 simple sequence repeats and 854 potential single nucleotide
      polymorphisms. CONCLUSION: The resource that these B. terrestris ESTs represent
      is valuable for ongoing work. The ESTs provide direct evidence of
      transcriptionally active regions, but they will also facilitate further
      functional genomics, gene discovery and future genome annotation. These are
      important aspects in obtaining a greater understanding of this key pollinator
      species.

PMID- 20156342
TI  - The genetic diversity and evolution of field pea (Pisum) studied by high
      throughput retrotransposon based insertion polymorphism (RBIP) marker analysis.
AB  - BACKGROUND: The genetic diversity of crop species is the result of natural
      selection on the wild progenitor and human intervention by ancient and modern
      farmers and breeders. The genomes of modern cultivars, old cultivated landraces,
      ecotypes and wild relatives reflect the effects of these forces and provide
      insights into germplasm structural diversity, the geographical dimension to
      species diversity and the process of domestication of wild organisms. This issue
      is also of great practical importance for crop improvement because wild germplasm
      represents a rich potential source of useful under-exploited alleles or allele
      combinations. The aim of the present study was to analyse a major Pisum germplasm
      collection to gain a broad understanding of the diversity and evolution of Pisum
      and provide a new rational framework for designing germplasm core collections of
      the genus. RESULTS: 3020 Pisum germplasm samples from the John Innes Pisum
      germplasm collection were genotyped for 45 retrotransposon based insertion
      polymorphism (RBIP) markers by the Tagged Array Marker (TAM) method. The data set
      was stored in a purpose-built Germinate relational database and analysed by both
      principal coordinate analysis and a nested application of the Structure program
      which yielded substantially similar but complementary views of the diversity of
      the genus Pisum. Structure revealed three Groups (1-3) corresponding
      approximately to landrace, cultivar and wild Pisum respectively, which were
      resolved by nested Structure analysis into 14 Sub-Groups, many of which correlate
      with taxonomic sub-divisions of Pisum, domestication related phenotypic traits
      and/or restricted geographical locations. Genetic distances calculated between
      these Sub-Groups are broadly supported by principal coordinate analysis and
      these, together with the trait and geographical data, were used to infer a
      detailed model for the domestication of Pisum. CONCLUSIONS: These data provide a
      clear picture of the major distinct gene pools into which the genus Pisum is
      partitioned and their geographical distribution. The data strongly support the
      model of independent domestications for P. sativum ssp abyssinicum and P.
      sativum. The relationships between these two cultivated germplasms and the
      various sub-divisions of wild Pisum have been clarified and the most likely
      ancestral wild gene pools for domesticated P. sativum identified. Lastly, this
      study provides a framework for defining global Pisum germplasm which will be
      useful for designing core collections.

PMID- 20156343
TI  - Endothelial dysfunction in obese non-hypertensive children without evidence of
      sleep disordered breathing.
AB  - BACKGROUND: Endothelial dysfunction is a complication of both obesity and
      obstructive sleep apnea syndrome (OSAS), the latter being highly prevalent among
      obese children. It is unknown whether obesity causes endothelial dysfunction in
      children in the absence of OSAS. This study examines endothelial function in
      obese and non-obese children without OSAS. METHODS: Pre-pubertal non-hypertensive
      children were recruited. Endothelial function was assessed in a morning fasted
      state, using a modified hyperemic test involving cuff-induced occlusion of the
      radial and ulnar arteries. The absence of OSAS was confirmed by overnight
      polysomnography. Anthropometry was also performed. RESULTS: 55 obese children
      (mean age 8.6 +/- 1.4 years, mean BMI z-score: 2.3 +/- 0.3) were compared to 50
      non-obese children (mean age 8.0 +/- 1.6 years, mean BMI z-score 0.3 +/- 0.9).
      Significant delays to peak capillary reperfusion after occlusion release occurred
      in obese compared to non-obese children (45.3 +/- 21.9 sec vs. 31.5 +/- 14.1 sec,
      p < 0.01), but no differences in the magnitude of hyperemia emerged. Time to peak
      reperfusion and percentage of body fat were positively correlated (r = 0.365, p <
      0.01). CONCLUSIONS: Our findings confirm that endothelial dysfunction occurs
      early in life in obese children, even in the absence of OSAS. Thus, mechanisms
      underlying endothelial dysfunction in pediatric obesity are operational in the
      absence of sleep-disordered breathing.

PMID- 20156344
TI  - Discontinuation of thyroid hormone treatment among children in the United States
      with congenital hypothyroidism: findings from health insurance claims data.
AB  - BACKGROUND: Thyroid hormone treatment in children with congenital hypothyroidism
      can prevent intellectual disability. Guidelines recommend that children diagnosed
      with congenital hypothyroidism through newborn screening remain on treatment to
      at least 3 years of age, after which a trial off therapy can determine which
      children have transient hypothyroidism. The purpose of this study was to describe
      the rate at which children with congenital hypothyroidism in the United States
      discontinue thyroid hormone treatment in early childhood. METHODS: Retrospective
      analysis of the 2002-2006 MarketScan(R) Commercial Claims and Encounters research
      databases and the 2001-2005 MarketScan Multi-State Medicaid databases. Children
      were classified as having congenital hypothyroidism based on billing codes and
      having filled a prescription for thyroid hormone treatment. Kaplan-Meier curve
      analysis was used to determine discontinuation rates. RESULTS: There were a total
      of 412 Medicaid-enrolled children and 292 privately-insured children with
      presumed congenital hypothyroidism included in this study. The overall birth
      prevalence of congenital hypothyroidism across both datasets was about 1 per
      2,300. By 36 months, the percentage who had discontinued thyroid replacement
      treatment was 38% (95% Confidence Interval: 32%-44%). Medicaid-enrolled children
      had a more rapid decline in the first 24 months of treatment compared to those
      with private insurance (P = 0.02). CONCLUSIONS: More than one-third of children
      treated for congenital hypothyroidism discontinued treatment within 36 months,
      which is inconsistent with current guidelines. It is not known how many of these
      children required continued treatment or experience adverse effects from
      discontinuation. These findings emphasize the critical need for follow-up systems
      to monitor the outcome of newborn screening.

PMID- 20156345
TI  - 'Pragmatic randomized controlled trial of individually prescribed exercise versus
      usual care in a heterogeneous cancer survivor population': a feasibility study
      PEACH trial: prescribed exercise after chemotherapy.
AB  - BACKGROUND: Many cancer survivors suffer a range of physical and psychological
      symptoms which may persist for months or years after cessation of treatment.
      Despite the known benefits of exercise and its potential to address many of the
      adverse effects of treatment, the role of exercise as well as optimum duration,
      frequency, and intensity in this population has yet to be fully elucidated. Many
      cancer rehabilitation programmes presented in the literature are very long and
      have tight eligibility criteria which make them non-applicable to the majority of
      cancer survivors. This paper presents the protocol of a novel 8-week intervention
      which aims to increase fitness, and address other physical symptoms in a
      heterogeneous cancer survivor population. METHODS/DESIGN: The aim is to recruit
      64 cancer survivors 2-6 months after completion of chemotherapy, usually
      adjuvant, with curative intent. Subjects will be recruited through oncology
      clinics in a single institution and randomised to usual care or an exercise
      intervention. The exercise intervention consists of two specifically tailored
      supervised moderate intensity aerobic exercise sessions weekly over 8-weeks. All
      participants will be assessed at baseline (0 weeks), at the end of the
      intervention (8 weeks), and at 3-month follow-up. The primary outcome measure is
      fitness, and secondary patient-related outcome measures include fatigue, quality
      of life, and morphological outcomes. A further secondary outcome is process
      evaluation including adherence to and compliance with the exercise program.
      DISCUSSION: This study will provide valuable information about the physical
      outcomes of this 8-week supervised aerobic programme. Additionally, process
      information and economic evaluation will inform the feasibility of implementing
      this program in a heterogeneous population post cessation of chemotherapy.

PMID- 20156346
TI  - Age-dependent role of steroids in the regulation of growth of the hen follicular
      wall.
AB  - BACKGROUND: The ovaries are the primary targets of senescence effects in
      mammalian and avian species. In the present study, relationships between
      reproductive aging, sex steroids and the growth pattern of the pre-ovulatory
      follicle wall were investigated using young hens with long clutch (YLC), old hens
      with long clutch (OLC), old hens with short clutch (OSC), and old hens with
      interrupted long clutch (OILC). METHODS: Experiment 1: Hens were sacrificed 1.5
      and 14.5 h after ovulation. Experiment 2: YLC and OILC hens were sacrificed 3.5 h
      after treatments with LH and/or aminoglutethimide (AG), an inhibitor of steroid
      synthesis. Volumes of pre-ovulatory follicles (F1-F5) and plasma concentrations
      of ovarian steroids were determined. Experiment 3: Granulosa and theca cells from
      F3 follicles of OSC and/or YLC hens were exposed in vitro to estradiol-17beta
      (E2), testosterone (T) and LH and the proliferative activity of the cells was
      examined using CellTiter 96 Aqueous One Solution Assay. RESULTS: In YLC and OLC
      groups, the total volume of F1-F5 follicles rose between 1.5 and 14.5 h after
      ovulation (P < 0.01), negatively correlating with the plasma level of E2 (P <
      0.01). There was no growth of pre-ovulatory follicles in the middle of the
      ovulatory cycle in the OSC group, with a positive correlation being present
      between E2 and the follicular volume (P < 0.05). In young hens, AG caused a rise
      in the total follicular volume. This rise was associated with a fall in E2 (r = 
      0.54, P < 0.05). E2 enhanced proliferation of granulosa cells from YLC and OSC
      groups. The proliferative activity of granulosa and theca cells of YLC hens
      depended on the interaction between T and LH (P < 0.01). CONCLUSIONS: These data
      indicate for the first time that the growth pattern of pre-ovulatory follicles
      during the ovulatory cycle changes in the course of reproductive aging. E2 seems
      to play a dual role in this adjustment; it stimulates the growth of the
      follicular wall in reproductive aged hens, whereas it may inhibit this process in
      young birds. T and LH are apparently involved in the growth regulation during the
      pre-ovulatory surge in young hens.

PMID- 20156347
TI  - The effects of a pre-workout supplement containing caffeine, creatine, and amino
      acids during three weeks of high-intensity exercise on aerobic and anaerobic
      performance.
AB  - BACKGROUND: A randomized, single-blinded, placebo-controlled, parallel design
      study was used to examine the effects of a pre-workout supplement combined with
      three weeks of high-intensity interval training (HIIT) on aerobic and anaerobic
      running performance, training volume, and body composition. METHODS: Twenty-four
      moderately-trained recreational athletes (mean +/- SD age = 21.1 +/- 1.9 yrs;
      stature = 172.2 +/- 8.7 cm; body mass = 66.2 +/- 11.8 kg, VO2max = 3.21 +/- 0.85
      l.min-1, percent body fat = 19.0 +/- 7.1%) were assigned to either the active
      supplement (GT, n = 13) or placebo (PL, n = 11) group. The active supplement
      (Game Time(R), Corr-Jensen Laboratories Inc., Aurora, CO) was 18 g of powder, 40
      kcals, and consisted of a proprietary blend including whey protein, cordyceps
      sinensis, creatine, citrulline, ginseng, and caffeine. The PL was also 18 g of
      powder, 40 kcals, and consisted of only maltodextrin, natural and artificial
      flavors and colors. Thirty minutes prior to all testing and training sessions,
      participants consumed their respective supplements mixed with 8-10 oz of water.
      Both groups participated in a three-week HIIT program three days per week, and
      testing was conducted before and after the training. Cardiovascular fitness
      (VO2max) was assessed using open circuit spirometry (Parvo-Medics TrueOne(R) 2400
      Metabolic Measurement System, Sandy, UT) during graded exercise tests on a
      treadmill (Woodway, Pro Series, Waukesha, WI). Also, four high-speed runs to
      exhaustion were conducted at 110, 105, 100, and 90% of the treadmill velocity
      recorded during VO2max, and the distances achieved were plotted over the times-to
      exhaustion. Linear regression was used to determine the slopes (critical
      velocity, CV) and y-intercepts (anaerobic running capacity, ARC) of these
      relationships to assess aerobic and anaerobic performances, respectively.
      Training volumes were tracked by summing the distances achieved during each
      training session for each subject. Percent body fat (%BF) and lean body mass
      (LBM) were assessed with air-displacement plethysmography (BOD POD(R), Life
      Measurement, Inc., Concord, CA). RESULTS: Both GT and PL groups demonstrated a
      significant (p = 0.028) increase in VO2max from pre- to post-training resulting
      in a 10.3% and 2.9% improvement, respectively. CV increased (p = 0.036) for the
      GT group by 2.9%, while the PL group did not change (p = 0.256; 1.7% increase).
      ARC increased for the PL group by 22.9% and for the GT group by 10.6%. Training
      volume was 11.6% higher for the GT versus PL group (p = 0.041). %BF decreased
      from 19.3% to 16.1% for the GT group and decreased from 18.0% to 16.8% in the PL
      group (p = 0.178). LBM increased from 54.2 kg to 55.4 kg (p = 0.035) for the GT
      group and decreased from 52.9 kg to 52.4 kg in the PL group (p = 0.694).
      CONCLUSION: These results demonstrated improvements in VO2max, CV, and LBM when
      GT is combined with HIIT. Three weeks of HIIT alone also augmented anaerobic
      running performance, VO2max and body composition.

PMID- 20156348
TI  - Goal-directed intraoperative therapy based on autocalibrated arterial pressure
      waveform analysis reduces hospital stay in high-risk surgical patients: a
      randomized, controlled trial.
AB  - INTRODUCTION: Several studies have shown that goal-directed hemodynamic and fluid
      optimization may result in improved outcome. However, the methods used were
      either invasive or had other limitations. The aim of this study was to perform
      intraoperative goal-directed therapy with a minimally invasive, easy to use
      device (FloTrac/Vigileo), and to evaluate possible improvements in patient
      outcome determined by the duration of hospital stay and the incidence of
      complications compared to a standard management protocol. METHODS: In this
      randomized, controlled trial 60 high-risk patients scheduled for major abdominal
      surgery were included. Patients were allocated into either an enhanced
      hemodynamic monitoring group using a cardiac index based intraoperative
      optimization protocol (FloTrac/Vigileo device, GDT-group, n = 30) or a standard
      management group (Control-group, n = 30), based on standard monitoring data.
      RESULTS: The median duration of hospital stay was significantly reduced in the
      GDT-group with 15 (12 - 17.75) days versus 19 (14 - 23.5) days (P = 0.006) and
      fewer patients developed complications than in the Control-group [6 patients
      (20%) versus 15 patients (50%), P = 0.03]. The total number of complications was
      reduced in the GDT-group (17 versus 49 complications, P = 0.001). CONCLUSIONS: In
      high-risk patients undergoing major abdominal surgery, implementation of an
      intraoperative goal-directed hemodynamic optimization protocol using the
      FloTrac/Vigileo device was associated with a reduced length of hospital stay and
      a lower incidence of complications compared to a standard management protocol.
      TRIAL REGISTRATION:  CLINICAL TRIAL REGISTRATION INFORMATION: Unique identifier:
      NCT00549419.

PMID- 20156349
TI  - Absence of xenotropic murine leukaemia virus-related virus in UK patients with
      chronic fatigue syndrome.
AB  - BACKGROUND: Detection of a retrovirus, xenotropic murine leukaemia virus-related
      virus (XMRV), has recently been reported in 67% of patients with chronic fatigue
      syndrome. We have studied a total of 170 samples from chronic fatigue syndrome
      patients from two UK cohorts and 395 controls for evidence of XMRV infection by
      looking either for the presence of viral nucleic acids using quantitative PCR
      (limit of detection <16 viral copies) or for the presence of serological
      responses using a virus neutralisation assay. RESULTS: We have not identified
      XMRV DNA in any samples by PCR (0/299). Some serum samples showed XMRV
      neutralising activity (26/565) but only one of these positive sera came from a
      CFS patient. Most of the positive sera were also able to neutralise MLV particles
      pseudotyped with envelope proteins from other viruses, including vesicular
      stomatitis virus, indicating significant cross-reactivity in serological
      responses. Four positive samples were specific for XMRV. CONCLUSIONS: No
      association between XMRV infection and CFS was observed in the samples tested,
      either by PCR or serological methodologies. The non-specific neutralisation
      observed in multiple serum samples suggests that it is unlikely that these
      responses were elicited by XMRV and highlights the danger of over-estimating XMRV
      frequency based on serological assays. In spite of this, we believe that the
      detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in
      at least four human serum samples indicates that XMRV infection may occur in the
      general population, although with currently uncertain outcomes.

PMID- 20156350
TI  - Factors contributing to delay in parasite clearance in uncomplicated falciparum
      malaria in children.
AB  - BACKGROUND: Drug resistance in Plasmodium falciparum is common in many endemic
      and other settings but there is no clear recommendation on when to change therapy
      when there is delay in parasite clearance after initiation of therapy in African
      children. METHODS: The factors contributing to delay in parasite clearance,
      defined as a clearance time > 2 d, in falciparum malaria were characterized in
      2,752 prospectively studied children treated with anti-malarial drugs between
      1996 and 2008. RESULTS: 1,237 of 2,752 children (45%) had delay in parasite
      clearance. Overall 211 children (17%) with delay in clearance subsequently failed
      therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291
      children. The following were independent risk factors for delay in parasite
      clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio
      [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of
      fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR =
      2.21, 95% CI = 1.77-2.75, P < 0.0001), and enrolment before year 2000 (AOR= 1.55,
      95% CI = 1.22-1.96, P < 0.0001). Following treatment, a body temperature >or= 38
      degrees C and parasitaemia > 20000/microl a day after treatment began, were
      independent risk factors for delay in clearance. Non-artemisinin monotherapies
      were associated with delay in clearance and treatment failures, and in those
      treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in
      clearance significantly increased gametocyte carriage (P < 0.0001). CONCLUSION:
      Delay in parasite clearance is multifactorial, is related to drug resistance and
      treatment failure in uncomplicated malaria and has implications for malaria
      control efforts in sub-Saharan Africa.

PMID- 20156351
TI  - Effect of anti-glycosphingolipid monoclonal antibodies in pathogenic fungal
      growth and differentiation. Characterization of monoclonal antibody MEST-3
      directed to Manpalpha1-->3Manpalpha1-->2IPC.
AB  - BACKGROUND: Studies carried out during the 1990's demonstrated the presence of
      fungal glycoinositol phosphorylceramides (GIPCs) with unique structures, some of
      them showed reactivity with sera of patients with histoplasmosis,
      paracoccidioidomycosis or aspergillosis. It was also observed that fungal GIPCs
      were able to inhibit T lymphocyte proliferation "in vitro", and studies regarding
      the importance of these molecules to fungal survival showed that many species of
      fungi are vulnerable to inhibitors of sphingolipid biosynthesis. RESULTS: In this
      paper, we describe a detailed characterization of an IgG2a monoclonal antibody
      (mAb), termed MEST-3, directed to the Paracoccidioides brasiliensis glycolipid
      antigen Pb-2 (Manpalpha1-->3Manpalpha1-->2IPC). mAb MEST-3 also recognizes GIPCs
      bearing the same structure in other fungi. Studies performed on fungal cultures
      clearly showed the strong inhibitory activity of MEST-3 on differentiation and
      colony formation of Paracoccidioides brasiliensis, Histoplasma capsulatum and
      Sporothrix schenckii. Similar inhibitory results were observed when these fungi
      where incubated with a different mAb, which recognizes GIPCs bearing terminal
      residues of beta-D-galactofuranose linked to mannose (mAb MEST-1). On the other
      hand, mAb MEST-2 specifically directed to fungal glucosylceramide (GlcCer) was
      able to promote only a weak inhibition on fungal differentiation and colony
      formation. CONCLUSIONS: These results strongly suggest that mAbs directed to
      specific glycosphingolipids are able to interfere on fungal growth and
      differentiation. Thus, studies on surface distribution of GIPCs in yeast and
      mycelium forms of fungi may yield valuable information regarding the relevance of
      glycosphingolipids in processes of fungal growth, morphological transition and
      infectivity.

PMID- 20156352
TI  - Prevalence of HPV infection among Greek women attending a gynecological
      outpatient clinic.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is a causative factor for
      cervical cancer. Early detection of high risk HPV types might help to identify
      women at high risk of cervical cancer. The aim of the present study was to
      examine the HPV prevalence and distribution in cervical smears in a sample of
      Greek women attending a gynecological outpatient clinic and to explore the
      determinants of the infection. METHODS: A total of 225 women were studied. All
      women underwent a regular gynecological control. 35 HPV types were studied; 6,
      11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59,
      61, 62, 66, 68, 70, 71, 72, 73, 81, 82, 83, 84, 85 and 89. Also, basic
      demographic information, sociodemographic characteristics and sexual behavior
      were recorded. RESULTS: HPV was detected in 22.7% of the study population. The
      percentage of the newly diagnosed women with HPV infection was 17.3%. HPV-16 was
      the most common type detected (5.3%) followed by HPV-53 (4.9%). 66.2% of the
      study participants had a Pap test during the last year without any abnormalities.
      HPV infection was related positively with alcohol consumption (OR: 2.19, 95% CI:
      1.04-4.63, P = 0.04) and number of sexual partners (OR: 2.16, 95% CI: 1.44-3.25,
      P < 0.001), and negatively with age (OR: 0.93, 95% CI: 0.87-0.99, P = 0.03), and
      monthly income (OR: 0.63, 95% CI: 0.44-0.89, P = 0.01). CONCLUSION: The
      prevalence of HPV in women attending an outpatient clinic is high. Number of
      sexual partners and alcohol consumption were the most significant risk factors
      for HPV infection, followed by young age and lower income.

PMID- 20156353
TI  - Bayesian aggregation versus majority vote in the characterization of non-specific
      arm pain based on quantitative needle electromyography.
AB  - BACKGROUND: Methods for the calculation and application of quantitative
      electromyographic (EMG) statistics for the characterization of EMG data detected
      from forearm muscles of individuals with and without pain associated with
      repetitive strain injury are presented. METHODS: A classification procedure using
      a multi-stage application of Bayesian inference is presented that characterizes a
      set of motor unit potentials acquired using needle electromyography. The utility
      of this technique in characterizing EMG data obtained from both normal
      individuals and those presenting with symptoms of "non-specific arm pain" is
      explored and validated. The efficacy of the Bayesian technique is compared with
      simple voting methods. RESULTS: The aggregate Bayesian classifier presented is
      found to perform with accuracy equivalent to that of majority voting on the test
      data, with an overall accuracy greater than 0.85. Theoretical foundations of the
      technique are discussed, and are related to the observations found. CONCLUSIONS:
      Aggregation of motor unit potential conditional probability distributions
      estimated using quantitative electromyographic analysis, may be successfully used
      to perform electrodiagnostic characterization of "non-specific arm pain." It is
      expected that these techniques will also be able to be applied to other types of
      electrodiagnostic data.

PMID- 20156354
TI  - Evidence-ranked motif identification.
AB  - cERMIT is a computationally efficient motif discovery tool based on analyzing
      genome-wide quantitative regulatory evidence. Instead of pre-selecting promising
      candidate sequences, it utilizes information across all sequence regions to
      search for high-scoring motifs. We apply cERMIT on a range of direct binding and
      overexpression datasets; it substantially outperforms state-of-the-art approaches
      on curated ChIP-chip datasets, and easily scales to current mammalian ChIP-seq
      experiments with data on thousands of non-coding regions.

PMID- 20156355
TI  - Fatty-acid binding protein 4 gene variants and childhood obesity: potential
      implications for insulin sensitivity and CRP levels.
AB  - INTRODUCTION: Obesity increases the risk for insulin resistance and metabolic
      syndrome in both adults and children. FABP4 is a member of the intracellular
      lipid-binding protein family that is predominantly expressed in adipose tissue,
      and plays an important role in maintaining glucose and lipid homeostasis. The
      purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic
      variants, and explore potential associations with fasting glucose and insulin
      levels in young school-age children with and without obesity. METHODS: A total of
      309 consecutive children ages 5-7 years were recruited. Children were divided
      based on BMI z score into Obese (OB; BMI z score >1.65) and non-obese (NOB).
      Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured.
      HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4
      gene (rs1051231, rs2303519, rs16909233 and rs1054135), corresponding to several
      critical regions of the encoding FABP4 gene sequence were genotyped. RESULTS:
      Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL,
      hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the
      variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135
      allelic variant was increased in OB, and was associated with increased FABP4
      levels, while the presence of rs16909233 variant allele, although similar in OB
      and NOB, was associated with increased HOMA values. CONCLUSIONS: Childhood
      obesity is associated with higher FABP4 levels that may promote cardiometabolic
      risk. The presence of selective SNPs in the FABP4 gene may account for increased
      risk for insulin resistance or systemic inflammation in the context of obesity.

PMID- 20156356
TI  - An ethnobotanical survey of medicinal plants in Babungo, Northwest Region,
      Cameroon.
AB  - BACKGROUND: An ethnobotanical survey was undertaken to record information on
      medicinal plants from traditional medical practitioners in Babungo and to
      identify the medicinal plants used for treating diseases. METHODS: Traditional
      Medical Practitioners (TMP's) who were the main informants were interviewed using
      semi-structured questionnaires and open-ended conversations. Field trips were
      made to the sites where TMP's harvest plants. RESULTS: The survey identified and
      recorded 107 plants species from 54 plant families, 98 genera used for treating
      diseases in Babungo. The Asteraceae was the most represented plant family while
      herbs made up 57% of the total medicinal plants used. The leaf was the most
      commonly used plant part while concoction and decoction were the most common
      method of traditional drug preparation. Most medicinal plants (72%) are harvested
      from the wild and 45% of these have other non medicinal uses. Knowledge of the
      use of plants as medicines remains mostly with the older generation with few
      youth showing an interest. CONCLUSIONS: A divers number of plants species are
      used for treating different diseases in Babungo. In addition to their use as
      medicines, a large number of plants have other non medicinal uses. The youth
      should be encouraged to learn the traditional medicinal knowledge to preserve it
      from being lost with the older generation.

PMID- 20156357
TI  - Validation of reference genes for gene expression analysis in chicory (Cichorium
      intybus) using quantitative real-time PCR.
AB  - BACKGROUND: Quantitative real-time reverse transcriptase polymerase chain
      reaction (qRT-PCR) is a sensitive technique for quantifying gene expression
      levels. One or more appropriate reference genes must be selected to accurately
      compare mRNA transcripts across different samples and tissues. Thus far, only
      actin-2 has been used as a reference gene for qRT-PCR in chicory, and a full
      comparison of several candidate reference genes in chicory has not yet been
      reported. RESULTS: Seven candidate reference genes, including nicotinamide
      adenine dinucleotide dehydrogenase (NADHD), actin (ACT), beta-tubulin (TUB),
      glyceraldehyde-3-phosphate-dehydrogenase (GADPH), histone H3 (H3), elongation
      factor 1-alpha (EF) and 18S rRNA (rRNA) were selected to study the expression
      stability for normalisation of gene expression in chicory. Primer specificity and
      amplification efficiency were verified for each gene. The expression stability of
      these genes was analysed across chicory root and leaf tissues using geNorm,
      NormFinder and BestKeeper software. ACT, EF, and rRNA were the most stable genes
      as identified by the three different analysis methods. In addition, the use of
      ACT, EF and GAPDH as reference genes was illustrated by analysing 1-FEHII (FEHII)
      expression in chicory root and leaf tissues. These analyses revealed the
      biological variation in FEHII transcript expression among the tissues studied,
      and between individual plants. CONCLUSIONS: geNorm, NormFinder, and BestKeeper
      analyses indicated that ACT, EF and rRNA had the highest expression stability
      across leaf and root tissues, while GAPDH and NADHD showed relatively low
      expression stability. The results of this study emphasise the importance of
      validating reference genes for qRT-PCR analysis in chicory. The use of the most
      stable reference genes such as ACT and EF allows accurate normalisation of gene
      expression in chicory leaf and root tissues.

PMID- 20156358
TI  - A novel microRNA and transcription factor mediated regulatory network in
      schizophrenia.
AB  - BACKGROUND: Schizophrenia is a complex brain disorder with molecular mechanisms
      that have yet to be elucidated. Previous studies have suggested that changes in
      gene expression may play an important role in the etiology of schizophrenia, and
      that microRNAs (miRNAs) and transcription factors (TFs) are primary regulators of
      this gene expression. So far, several miRNA-TF mediated regulatory modules have
      been verified. We hypothesized that miRNAs and TFs might play combinatory
      regulatory roles for schizophrenia genes and, thus, explored miRNA-TF regulatory
      networks in schizophrenia. RESULTS: We identified 32 feed-forward loops (FFLs)
      among our compiled schizophrenia-related miRNAs, TFs and genes. Our evaluation
      revealed that these observed FFLs were significantly enriched in schizophrenia
      genes. By converging the FFLs and mutual feedback loops, we constructed a novel
      miRNA-TF regulatory network for schizophrenia. Our analysis revealed EGR3 and hsa
      miR-195 were core regulators in this regulatory network. We next proposed a model
      highlighting EGR3 and miRNAs involved in signaling pathways and regulatory
      networks in the nervous system. Finally, we suggested several single nucleotide
      polymorphisms (SNPs) located on miRNAs, their target sites, and TFBSs, which may
      have an effect in schizophrenia gene regulation. CONCLUSIONS: This study provides
      many insights on the regulatory mechanisms of genes involved in schizophrenia. It
      represents the first investigation of a miRNA-TF regulatory network for a complex
      disease, as demonstrated in schizophrenia.

PMID- 20156359
TI  - The relationship between CD4+CD25+CD127- regulatory T cells and inflammatory
      response and outcome during shock states.
AB  - INTRODUCTION: Although regulatory T lymphocytes (Tregs) have a pivotal role in
      preventing autoimmune diseases and limiting chronic inflammatory conditions, they
      may also block beneficial immune responses by preventing sterilizing immunity to
      certain pathogens. METHODS: To determine whether naturally occurring Treg cells
      have a role in inflammatory response and outcome during shock state we conducted
      an observational study in two adult ICUs from a university hospital. Within 12
      hours of admission, peripheral whole blood was collected for the measurement of
      cytokines and determination of lymphocyte count. Sampling was repeated at day
      three, five and seven. Furthermore, an experimental septic shock was induced in
      adult Balb/c mice through caecal ligation and puncture. RESULTS: Forty-three
      patients suffering from shock (26 septic, 17 non septic), and 7 healthy
      volunteers were included. The percentage of Tregs increased as early as 3 days
      after the onset of shock, while their absolute number remained lower than in
      healthy volunteers. A similar pattern of Tregs kinetics was found in infected and
      non infected patients. Though there was an inverse correlation between severity
      scores and Tregs percentage, the time course of Tregs was similar between
      survivors and non survivors. No relation between Tregs and cytokine concentration
      was found. In septic mice, although there was a rapid increase in Treg cells
      subset among splenocytes, antibody-induced depletion of Tregs before the onset of
      sepsis did not alter survival. CONCLUSIONS: These data argue against a
      determinant role of Tregs in inflammatory response and outcome during shock
      states.

PMID- 20156360
TI  - Risk factors for multidrug resistant bacteria and optimization of empirical
      antibiotic therapy in postoperative peritonitis.
AB  - INTRODUCTION: The main objective was to determine risk factors for presence of
      multidrug resistant bacteria (MDR) in postoperative peritonitis (PP) and optimal
      empirical antibiotic therapy (EA) among options proposed by Infectious Disease
      Society of America and the Surgical Infection Society guidelines. METHODS: One
      hundred patients hospitalised in the intensive care unit (ICU) for PP were
      reviewed. Clinical and microbiologic data, EA and its adequacy were analysed. The
      in vitro activities of 9 antibiotics in relation to the cultured bacteria were
      assessed to propose the most adequate EA among 17 regimens in the largest number
      of cases. RESULTS: A total of 269 bacteria was cultured in 100 patients including
      41 episodes with MDR. According to logistic regression analysis, the use of broad
      spectrum antibiotic between initial intervention and reoperation was the only
      significant risk factor for emergence of MDR bacteria (odds ratio (OR) = 5.1; 95%
      confidence interval (CI) = 1.7 - 15; P = 0.0031). Antibiotics providing the best
      activity rate were imipenem/cilastatin (68%) and piperacillin/tazobactam (53%).
      The best adequacy for EA was obtained by combinations of imipenem/cilastatin or
      piperacillin/tazobactam, amikacin and a glycopeptide, with values reaching 99%
      and 94%, respectively. Imipenem/cilastin was the only single-drug regimen
      providing an adequacy superior to 80% in the absence of broad spectrum antibiotic
      between initial surgery and reoperation. CONCLUSIONS: Interval antibiotic therapy
      is associated with the presence of MDR bacteria. Not all regimens proposed by
      Infectious Disease Society of America and the Surgical Infection Society
      guidelines for PP can provide an acceptable rate of adequacy. Monotherapy with
      imipenem/cilastin is suitable for EA only in absence of this risk factor for MDR.
      For other patients, only antibiotic combinations may achieve high adequacy rates.

PMID- 20156361
TI  - National variation in United States sepsis mortality: a descriptive study.
AB  - BACKGROUND: The regional distribution of a disease may provide important insights
      regarding its pathophysiology, risk factors and clinical care. While sepsis is a
      prominent cause of death in the United States (US), few studies have examined
      regional variations with this malady. We identified the national variation in
      sepsis deaths in the US. We conducted a descriptive analysis of 1999-2005
      national vital statistics data from the National Center for Health Statistics
      summarized at the state-level. We defined sepsis deaths as deaths attributed to
      an infection, classified according to the International Classification of
      Diseases, Version 10. We calculated national and state age-adjusted sepsis
      attributed mortality rates. RESULTS: National age-adjusted sepsis mortality was
      65.5 per 100,000 persons (95% CI: 65.8 - 66.0). State level sepsis mortality
      varied more than two-fold (range 41 to 88.6 per 100,000 persons; median 60.8 per
      100,000, IQR 53.9-74.4 per 100,000). A cluster extending from the Southeastern to
      the mid-Atlantic US encompassed states with the highest sepsis mortality.
      CONCLUSIONS: Sepsis mortality varies across the US. The states with highest
      sepsis mortality form a contiguous cluster in the Southeastern and mid-Atlantic
      US. These observations highlight unanswered questions regarding the
      characteristics and care of sepsis.

PMID- 20156362
TI  - Characteristics of primary health care units with focus on drug information from
      the pharmaceutical industry and adherence to prescribing objectives: a cross
      sectional study.
AB  - BACKGROUND: Adherence to prescribing guidelines varies between primary health
      care units. The aim of the present study was to investigate correlations between
      characteristics of primary health care units and adherence to prescribing
      objectives for rational drug use with focus on drug information from the
      pharmaceutical industry. METHODS: A cross-sectional study was performed in all 25
      primary health care units in Goteborg, Sweden. A questionnaire on characteristics
      of practice settings [(i) size of unit, (ii) profession of head, (iii) use of
      temporary physicians, (iv) drug information from the pharmaceutical industry, (v)
      producer-independent drug information, and (vi) education on prescribing for
      newly employed physicians] was sent to the heads of the units. A national sales
      register for prescribed drugs (Xplain) was used for evaluation of adherence to
      the six regional prescribing objectives concerning proton pump inhibitors (PPIs),
      angiotensin converting enzyme inhibitors (ACEIs), statins and antidepressants.
      RESULTS: Twenty-two out of 25 primary health care units responded to the
      questionnaire (response rate 88%). A physician as head and presence of producer
      independent drug information was positively correlated with adherence to the
      prescribing objectives (median number of prescribing objectives adhered to (25th 
      75th percentile): 2.5 (1-3.25) vs 1 (0-2), P = 0.013; 2 (1-3) vs 0, P = 0.043,
      respectively. Presence of drug information from the pharmaceutical industry and
      education on prescribing for newly employed physicians was negatively associated
      with adherence to the prescribing objectives: 1 (0-2) vs 3.5 (2.25-4.75), P =
      0.005; 1 (0-2) vs 3 (1.5-4), P = 0.034, respectively. CONCLUSION: Several
      characteristics of the primary health care units correlated with adherence to
      prescribing objectives for rational drug use. Further research on this topic is
      needed and would constitute valuable information for health care decision makers.

PMID- 20156363
TI  - Combined rotation scarf and Akin osteotomies for hallux valgus: a patient
      focussed 9 year follow up of 50 patients.
AB  - BACKGROUND: The Cochrane review of hallux valgus surgery has disputed the
      scientific validity of hallux valgus research. Scoring systems and surrogate
      measures such as x-ray angles are commonly reported at just one year post
      operatively but these are of dubious relevance to the patient. In this study we
      extended the follow up to a minimum of 8 years and sought to address patient
      specific concerns with hallux valgus surgery. The long term follow up also
      allowed a comprehensive review of the complications associated with the combined
      rotation scarf and Akin osteotomies. METHODS: Between 1996 and 1999, 101 patients
      underwent rotation scarf and Akin osteotomies for the treatment of hallux valgus.
      All patients were contacted and asked to participate in this study. 50 female
      participants were available allowing review of 73 procedures. The average follow
      up was over 9 years and the average age at the time of surgery was 57. The
      participants were physically examined and interviewed. RESULTS: Post-operatively,
      in 86% of the participants there were no footwear restrictions. Stiffness of the
      first metatarsophalangeal joint was reported in 8% (6 feet); 10% were unhappy
      with the cosmetic appearance of their feet, 3 feet had hallux varus, and 2 feet
      had recurrent hallux valgus. There were no foot-related activity restrictions in
      92% of the group. Metatarsalgia occurred in 4% (3 feet). 96% were better than
      before surgery and 88% were completely satisfied with their post-operative
      result. Hallux varus was the greatest single cause of dissatisfaction. The most
      common adverse event in the study was internal fixation irritation. Hallux valgus
      surgery is not without risk and these findings could be useful in the informed
      consent process. CONCLUSIONS: When combined the rotation scarf and Akin
      osteotomies are an effective treatment for hallux valgus that achieves good long
      term correction with a low incidence of recurrence, footwear restriction or
      metatarsalgia. The nature of the osteotomies allows early return to normal shoes
      and activity without the need for postoperative immobilisation in a plaster cast.

PMID- 20156364
TI  - Kinematic aspects of trunk motion and gender effect in normal adults.
AB  - BACKGROUND: The purpose of this study was to analyze kinematic trunk motion data
      in normal adults and to investigate gender effect. METHODS: Kinematic trunk
      motion data were obtained for 20 healthy subjects (11 men and 9 women; age from
      21 to 40 years) during walking a 9 m long lane at a self selected speed, namely,
      motions in the sagittal (tilt), coronal (obliquity), and transverse (rotation)
      planes, which were all expressed as motions in global (relative to the ground)
      and those in pelvic reference frame (relative to pelvis), i.e., tilt (G),
      obliquity (G), rotation (G), tilt (P), obliquity (P), rotation (P). RESULTS:
      Range of tilt (G), obliquity (G) and rotation (G) showed smaller motion than that
      of tilt (P), obliquity (P) and rotation (P), respectively. When genders were
      compared, female trunks showed a 5 degree more extended posture during gait than
      male trunks (p = 0.002), which appeared to be caused by different lumbar
      lordosis. Ranges of coronal and transverse plane motion appeared to be
      correlated. In gait cycle, the trunk motion appeared to counterbalance the lower
      extremity during swing phase in sagittal plane, and to reduce the angular
      velocity toward the contralateral side immediate before the contralateral heel
      strike in the coronal plane. CONCLUSIONS: Men and women showed different lumbar
      lordosis during normal gait, which might be partly responsible for the different
      prevalence of lumbar diseases between genders. However, this needs further
      investigation.

PMID- 20156365
TI  - The resident-as-teacher educational challenge: a needs assessment survey at the
      National Autonomous University of Mexico Faculty of Medicine.
AB  - BACKGROUND: The role of residents as educators is increasingly recognized, since
      it impacts residents, interns, medical students and other healthcare
      professionals. A widespread implementation of resident-as-teacher courses in
      developed countries' medical schools has occurred, with variable results. There
      is a dearth of information about this theme in developing countries. The National
      Autonomous University of Mexico (UNAM) Faculty of Medicine has more than 50% of
      the residency programs' physician population in Mexico. This report describes a
      needs assessment survey for a resident as teacher program at our institution.
      METHODS: A cross-sectional descriptive survey was developed based on a review of
      the available literature and discussion by an expert multidisciplinary committee.
      The goal was to identify the residents' attitudes, academic needs and preferred
      educational strategies regarding resident-as-teacher activities throughout the
      residency. The survey was piloted and modified accordingly. The paper anonymous
      survey was sent to 7,685 residents, the total population of medical residents in
      UNAM programs in the country. RESULTS: There was a 65.7% return rate (5,186
      questionnaires), a broad and representative sample of the student population. The
      residents felt they had knowledge and were competent in medical education, but
      the majority felt a need to improve their knowledge and skills in this
      discipline. Most residents (92.5%) felt that their role as educators of medical
      students, interns and other residents was important/very important. They
      estimated that 45.5% of their learning came from other residents. Ninety percent
      stated that it was necessary to be trained in teaching skills. The themes
      identified to include in the educational intervention were mostly clinically
      oriented. The educational strategies in order of preference were interactive
      lectures with a professor, small groups with a moderator, material available in a
      website for self-learning, printed material for self-study and homework, and
      small group web-based learning. CONCLUSIONS: There is a large unmet need to
      implement educational interventions to improve residents' educational skills in
      postgraduate educational programs in developing countries. Most perceived needs
      of residents are practical and clinically oriented, and they prefer traditional
      educational strategies. Resident as teachers educational interventions need to be
      designed taking into account local needs and resources.

PMID- 20156366
TI  - TrkB is highly expressed in NSCLC and mediates BDNF-induced the activation of
      Pyk2 signaling and the invasion of A549 cells.
AB  - BACKGROUND: Aberrant regulation in the invasion of cancer cells is closely
      associated with their metastatic potentials. TrkB functions as a receptor
      tyrosine kinase and is considered to facilitate tumor metastasis. Pyk2 is a non
      receptor tyrosine kinase and integrates signals in cell invasion. However, little
      is known about the expression of TrkB in NSCLC and whether Pyk2 is involved in
      TrkB-mediated invasion of A549 cells. METHODS: The expression of TrkB was
      investigated in NSCLC by immunohistochemical staining. Both HBE and A549 cells
      were treated with BDNF. The expression of TrkB, Pyk2 and ERK phosphorylations
      were assessed by western blot. Besides, A549 cells were transfected with TrkB
      siRNA or Pyk2-siRNA, or treated with ERK inhibitor where indicated. Transwell
      assay was performed to evaluate cell invasion. RESULTS: 40 cases (66.7%) of NSCLC
      were found higher expression of TrkB and patients with more TrkB expression had
      significant metastatic lymph nodes (p = 0.028). BDNF facilitated the invasion of
      A549 cells and the activations of Pyk2 in Tyr402 and ERK. However, the effects of
      BDNF were not observed in HBE cells with lower expression of TrkB. In addition,
      the increased Pyk2 and ERK activities induced by BDNF were significantly
      inhibited by blocking TrkB expression, so was the invasion of A549 cells.
      Knockdown studies revealed the essential role of Pyk2 for BDNF-induced cell
      invasion, since the invasion of A549 cells was abolished by Pyk2-siRNA. The
      application of ERK inhibitor also showed the suppressed ERK phosphorylation and
      cell invasion. CONCLUSION: These data indicated that higher expression of TrkB in
      NSCLC was closely correlated with lymph node metastasis, and BDNF probably via
      TrkB/Pyk2/ERK promoted the invasion of A549 cells.

PMID- 20156367
TI  - Functional cooperation between FACT and MCM is coordinated with cell cycle and
      differential complex formation.
AB  - BACKGROUND: Functional cooperation between FACT and the MCM helicase complex
      constitutes an integral step during DNA replication initiation. However, mode of
      regulation that underlies the proper functional interaction of FACT and MCM is
      poorly understood. METHODS & RESULTS: Here we present evidence indicating that
      such interaction is coordinated with cell cycle progression and differential
      complex formation. We first demonstrate the existence of two distinct FACT-MCM
      subassemblies, FACT-MCM2/4/6/7 and FACT-MCM2/3/4/5. Both complexes possess DNA
      unwinding activity and are subject to cell cycle-dependent enzymatic regulation.
      Interestingly, analysis of functional attributes further suggests that they act
      at distinct, and possibly sequential, steps during origin establishment and
      replication initiation. Moreover, we show that the phosphorylation profile of the
      FACT-associated MCM4 undergoes a cell cycle-dependent change, which is directly
      correlated with the catalytic activity of the FACT-MCM helicase complexes.
      Finally, at the quaternary structure level, physical interaction between FACT and
      MCM complexes is generally dependent on persistent cell cycle and further
      stabilized upon S phase entry. Cessation of mitotic cycle destabilizes the
      complex formation and likely leads to compromised coordination and activities.
      CONCLUSIONS: Together, our results correlate FACT-MCM functionally and temporally
      with S phase and DNA replication. They further demonstrate that enzymatic
      activities intrinsically important for DNA replication are tightly controlled at
      various levels, thereby ensuring proper progression of, as well as exit from, the
      cell cycle and ultimately euploid gene balance.

PMID- 20156369
TI  - Acquired cholesteatoma pathogenesis: stepwise explanations.
AB  - BACKGROUND: Since Virchow's first, 1855 publication on cholesteatoma, this
      disease has been the subject of extensive debate. The pathogenesis of acquired
      cholesteatoma is repeatedly explained on the premises of the migration,
      hyperplasia and metaplasia theories, but proof for the latter theory remains
      limited. In retrospect, there is progress toward better understanding of all the
      pathological mechanisms involved, as expounded in this review. DISCUSSION: The
      triggers for cholesteatoma onset are diverse, and may involve tympanic membrane
      trauma (i.e. perforation, displacement, retraction or invagination), tympanic
      membrane disease, and/or tympanic cavity mucosa disease. Research has revealed
      that cell migration is replaced under inflammatory conditions by hyperplasia,
      which triggers the onset of cholesteatoma. Lately, the hyperplasia theory gained
      prominence and circumscription of the papillary cone formation concept provided
      insight into cholesteatoma progression (growth and expansion). Diseased mucosa
      can contribute to the development of retraction pockets and cholesteatoma. The
      type of cholesteatoma trigger and the role of chronic inflammation during disease
      progression and recurrence are important in guiding clinical intervention.

PMID- 20156368
TI  - The effect of the COACH program (Continuity Of Appropriate pharmacotherapy,
      patient Counselling and information transfer in Healthcare) on readmission rates
      in a multicultural population of internal medicine patients.
AB  - BACKGROUND: Medication errors occur frequently at points of transition in care.
      The key problems causing these medication errors are: incomplete and
      inappropriate medication reconciliation at hospital discharge (partly arising
      from inadequate medication reconciliation at admission), insufficient patient
      information (especially within a multicultural patient population) and
      insufficient communication to the next health care provider. Whether
      interventions aimed at the combination of these aspects indeed result in less
      discontinuity and associated harm is uncertain. Therefore the main objective of
      this study is to determine the effect of the COACH program (Continuity Of
      Appropriate pharmacotherapy, patient Counselling and information transfer in
      Healthcare) on readmission rates in patients discharged from the internal
      medicine department. METHODS/DESIGN: An experimental study is performed at the
      internal medicine ward of a general teaching hospital in Amsterdam, which serves
      a multicultural population. In this study the effects of the COACH program is
      compared with usual care using a pre-post study design. All patients being
      admitted with at least one prescribed drug intended for chronic use are included
      in the study unless they meet one of the following exclusion criteria: no
      informed consent, no medication intended for chronic use prescribed at discharge,
      death, transfer to another ward or hospital, discharge within 24 hours or out of
      office hours, discharge to a nursing home and no possibility to counsel the
      patient.The intervention consists of medication reconciliation, patient
      counselling and communication between the hospital and primary care healthcare
      providers.The following outcomes are measured: the primary outcome readmissions
      within six months after discharge and the secondary outcomes number of
      interventions, adherence, patient's attitude towards medicines, patient's
      satisfaction with medication information, costs, quality of life and finally
      satisfaction of general practitioners and community pharmacists.Interrupted time
      series analysis is used for data-analysis of the primary outcome. Descriptive
      statistics is performed for the secondary outcomes. An economic evaluation is
      performed according to the intention-to-treat principle. DISCUSSION: This study
      will be able to evaluate the clinical and cost impact of a comprehensive program
      on continuity of care and associated patient safety. TRIAL REGISTRATION: Dutch
      trial register: NTR1519.

PMID- 20156370
TI  - Management and clinical outcome of sinonasal teratocarcinosarcoma: single
      institution experience.
AB  - PURPOSE: To study the outcome of patients with sinonasal teratocarcinosarcoma
      treated at a single institution. METHODS: We reviewed the medical records of 22
      patients with histopathologically proven sinonasal teratocarcinosarcoma diagnosed
      during the period 1993-2007. Treatment was completed in 16 patients. RESULTS:
      Fourteen patients underwent surgery (six received craniofacial resection, four
      open surgery and four endoscopic resection); this was followed by radiation
      therapy with or without chemotherapy in 11 patients. Two patients received
      chemoradiation as the definitive treatment. At median follow up in surviving
      patients of 34 months (range one to 180 months), only five were controlled.
      Disease recurred in 11 patients, with a median time to recurrence of seven
      months. The two-year disease-free survival rate and the overall survival rate
      were 28 and 46 per cent, respectively. CONCLUSION: Sinonasal teratocarcinosarcoma
      appears to be an aggressive disease, with the majority of patients suffering
      locoregional failure. Multimodality treatment, in the form of a combination of
      surgery, radiation therapy and chemotherapy, appears to be the optimal approach.

PMID- 20156371
TI  - Complete congenital third branchial fistula with left-sided, recurrent,
      suppurative thyroiditis.
AB  - OBJECTIVE: We report an extremely rare case of a complete congenital third
      branchial arch fistula in a nine-year-old boy. METHOD: A case report and a review
      of the English literature concerning third branchial arch fistula of congenital
      origin are presented. RESULTS: A nine-year-old boy presented with a history of a
      small opening in the middle third of the anterior neck since birth, with
      recurrent surrounding swelling. There was no history of surgical drainage or
      spontaneous rupture. Computed tomography with contrast injection into the
      external cervical opening revealed a patent tract from the neck skin to the base
      of the pyriform sinus. Complete excision of the tract up to the pyriform sinus
      with left hemithyroidectomy was performed. Follow up at 22 months showed no
      recurrence. CONCLUSION: To our knowledge, this case represents a very rare
      occurrence of the congenital variety of complete third branchial arch fistula at
      an unusual site. This case indicates that third branchial arch fistula can be
      complete, and may present in the anterior neck, an unusual site. In such cases,
      computed tomography fistulography and injection of dye into the pyriform sinus
      enables intra-operative delineation of the tract.

PMID- 20156372
TI  - Internal jugular vein thrombosis secondary to a permanent cardiac pacemaker: an
      unusual case of lateral neck swelling.
AB  - OBJECTIVE: To describe an unusual case of lateral neck swelling in a patient with
      a permanent cardiac pacemaker. CASE REPORT: We describe a patient who presented
      with a painful, lateral neck swelling due to an internal jugular vein thrombus.
      This thrombus originated from around pacemaker wires in the subclavian vein. This
      case is unusual, as the vast majority of thromboses in patients with cardiac
      pacemakers are found in the subclavian vein alone. We also review the literature
      on the relationship between cardiac pacemakers and internal jugular vein
      thrombosis, and on the management of the latter. CONCLUSION: Our patient
      illustrates a rare cause of a painful, lateral neck swelling: an internal jugular
      vein thrombus secondary to a cardiac pacemaker. Clinicians should be wary of such
      pathology in similar patients, in order to ensure early treatment and avoidance
      of complications.

PMID- 20156374
TI  - Doctor google and the internet prescription.

PMID- 20156373
TI  - Inflammatory myofibroblastic tumour of the tonsil: case report and literature
      review.
AB  - OBJECTIVE: We present the first reported case in the English language literature
      of an inflammatory myofibroblastic tumour of the right tonsil in a young,
      pregnant woman, and we report a management strategy for this enigmatic entity.
      CASE REPORT: A 28-year-old, pregnant woman presented with a 10-day history of
      odynophagia despite a course of antibiotics. Examination revealed a grade II,
      erythematous right tonsil with ulceration on the upper pole. A biopsy was
      arranged, and initial evaluation was suggestive of spindle cell carcinoma.
      However, this diagnosis was reviewed after immunohistochemical staining confirmed
      an inflammatory myofibroblastic tumour. Subsequent complete excision was
      undertaken using CO2 laser. CONCLUSION: Clinically, inflammatory myofibroblastic
      tumour of the tonsil is known to be locally aggressive and can present in a
      manner not dissimilar to a high grade carcinoma of the tonsil. As a result, the
      recommended treatment is complete local excision with careful follow up.

PMID- 20156375
TI  - Legends in urology.

PMID- 20156376
TI  - Feasibility of using guidelines to choose treatment for prostate cancer.
AB  - INTRODUCTION: Treatment for localized prostate cancer (LPC) may not improve
      survival and commonly impairs health related quality of life. National guidelines
      provide algorithms to choose between treatment or observation for LPC, but the
      algorithms require the factoring of the patient's baseline comorbidity adjusted
      life expectancy (CALE). However, no method is available to estimate CALE of 10 or
      more years. MATERIALS AND METHODS: A mailed survey was completed by newly
      diagnosed untreated LPC patients. Their baseline CALE was estimated by weighting
      their age based life expectancy by quartiles of comorbidity scores, and a
      national guideline was used to find if treatment or observation was recommended
      for each patient. Demographic, health and cancer characteristics, and beliefs
      were compared in patients who chose treatment or observation concordant with the
      guideline, and those who chose under treatment or over treatment. RESULTS: Of 184
      survey participants, 10 chose under treatment, 144 chose concordant treatment,
      and 30 chose over treatment. Under treatment patients had similar
      sociodemographic and health characteristics to patients who were concordant. In
      comparison to concordant patients, over treatment patients were older, had a
      lower Gleason grade or PSA level, a higher comorbidity score, a lower CALE, and
      lower scores on the Fear of Cancer Recurrence scale. CONCLUSION: Comorbidity
      scores can be used to estimate CALE in LPC patients, and estimation of CALE
      allows the use of guidelines in the choice of treatment. In our study, over
      treatment occurred more frequently than under treatment. Factors known to limit
      the survival benefit of treatment were associated with over treatment. Over
      treatment patients also had lower fear of cancer recurrence.

PMID- 20156377
TI  - Accuracy of ultrasound in estimation of prostate weight: comparison of urologists
      and radiologists.
AB  - INTRODUCTION: Measurements of prostate size are obtained to contribute in the
      diagnosis and follow up of patients with a variety of diseases. Since its
      introduction, transrectal ultrasonography (TRUS) of the prostate has become the
      most common method for assessment of prostate volumes. Ultrasonography, in
      general, has been associated with concerns of operator dependent variability.
      Herein, we analyze the accuracy of urologists and radiologists performing TRUS.
      MATERIAL AND METHODS: The accuracy of preoperative TRUS prostate volume
      estimation was evaluated by comparing it to gross specimen prostate weight
      following robot-assisted radical prostatectomy (RARP) performed from August 2004
      to March 2008 in Mayo Clinic Arizona. A total of 800 RARPs were evaluated
      retrospectively with 302 patients having a prostate volume measurement with TRUS
      at our institution followed by RARP being performed within 30 days. The TRUS
      measurements were divided into two groups: those TRUS measurements performed by
      urologists (group 1), and those performed by radiologists (group 2). The accuracy
      of the two groups were compared using a Pearson correlation analysis. RESULTS:
      The estimated weight by TRUS in the total cohort of patients correlated with the
      pathological specimen weight at 0.802 with a standard error of 0.90. Group 1
      performed a total of 114 ultrasounds with a correlation of 0.835 and a standard
      error of 1.27. Group 2 performed a total of 188 with a correlation of 0.786 and a
      standard error of 0.88. CONCLUSIONS: Urologists and radiologists are both
      consistently within 17%-22% of the estimated prostate specimen weight. Urologists
      appeared to have a slightly higher accuracy in estimation but a higher range of
      error for the whole group when compared to radiologists. Transrectal
      ultrasonography is a reliable technique to estimate prostate weight and accuracy
      to within 20% of the pathological weight. Urologists and radiologists are
      essentially equally proficient in estimating prostate weight with TRUS. These
      findings are particularly important with respect to specialty certification and
      competency/proficiency evaluation, as health care increasingly moves towards
      outcomes based reimbursement.

PMID- 20156378
TI  - Increased nerve growth factor in neurogenic overactive bladder and interstitial
      cystitis patients.
AB  - OBJECTIVES: Studies have suggested that pathology of the lower urinary tract can
      be detected by following changes in urinary proteins. We evaluated urine nerve
      growth factor (NGF) levels from patients with a variety of urologic conditions to
      examine NGF's role as a future biomarker. MATERIALS AND METHODS: Urine samples
      were obtained from 72 patients with normal non-diseased urinary tracts (n = 13),
      neurogenic overactive bladder (NOAB) (n = 13), idiopathic overactive bladder
      (OAB) (n = 17), interstitial cystitis/painful bladder syndrome (IC/PBS) (n = 8),
      prostate cancer (n = 7), history of prostate cancer status post robot-assisted
      laparoscopic prostatectomy (RALP) (n = 6), active bladder cancer (n = 4), and
      nephrolithiasis (n = 4). Urinary NGF levels were measured by enzyme linked
      immunosorbent assay (ELISA) using the Emax ImmunoAssay System (Promega, Madison,
      WI, USA); each NGF level was normalized to the patient's urine creatinine (Cr)
      level. The Bonferroni correction was used to adjust for multiple comparisons.
      RESULTS: Urinary NGF/Cr levels were significantly elevated in patients with NOAB
      (23.02 pg/mg (0-293), p = 0.004) and IC/PBS (31.24 pg/mg (0-291), p = 0.006); and
      approached significance in patients with nephrolithiasis (19.46 pg/mg (0-85), p =
      0.06) compared to controls (0.00 pg/mg (0-12). CONCLUSIONS: Urinary NGF levels
      were significantly elevated in patients with NOAB and IC/PBS. Future studies are
      needed to further examine the significance of urinary NGF levels in the
      pathogenesis of a variety of urologic diseases and whether NGF could be used as a
      diagnostic or prognostic marker for specific urologic diseases.

PMID- 20156379
TI  - Defining success following sling surgery: association of satisfaction with
      patient reported outcomes.
AB  - AIMS: The assessment of incontinence therapies is complicated by the variety of
      patient reported outcomes (PRO) measures used in research protocol. Patient
      satisfaction may be one of the most relevant albeit complex PRO measures and is a
      function of many related variables. We sought to assess the relationship between
      patient satisfaction and other PRO. METHODS: A retrospective review of patients
      undergoing SPARC (n = 314) and autologous rectus pubovaginal sling (PVS) (n =
      127) was performed, with 204 (SPARC) and 67 (PVS) patients completing
      questionnaire surveillance and minimum 12 month follow up. Outcomes were assessed
      using validated incontinence questionnaires (UDI-6, IIQ-7) supplemented with
      additional items addressing subjective improvement. Comparisons were made between
      patients reporting a willingness to recommend and repeat surgical intervention
      (combined variable, satisfaction surrogate) and achievement of defined endpoints
      in the remaining outcome measures. RESULTS: A large difference in outcomes was
      seen depending on PRO measure analyzed. Dry was the strictest measure used (33%,
      SPARC; 39%, PVS; p = NS), while >or= 50% improvement was reported with the
      greatest frequency (75%, SPARC; 73%, PVS; p = NS). With the exception of pad use,
      a statistically significant association between all PRO measures and the
      willingness to recommend/repeat surgery was identified. CONCLUSIONS: Our data
      demonstrate an association between a variety of PRO measures and patient reported
      satisfaction. Based on this finding, the development of a simplified and
      standardized PRO instrument, one that maintains an accurate reflection of patient
      satisfaction and is less cumbersome for the patient may be possible.

PMID- 20156380
TI  - Status of robot-assisted radical cystectomy.
AB  - PURPOSE: Robot-assisted radical cystectomy (RARC) is an alternative approach for
      treatment of bladder cancer. We provide a critical review of the current status
      of RARC and pelvic lymph node dissection with a focus on feasibility, safety and
      oncological efficacy of the procedure. MATERIALS AND METHODS: The PubMed
      literature database was reviewed for RARC series that have been reported in the
      English language until the present time. Surgical technique, operative
      parameters, pathologic outcome, complications and quality of life were examined.
      RESULTS: RARC is progressing steadily. With nearly 500 published cases worldwide,
      RARC proves to be technically feasible and oncologically effective. It is
      associated with less blood loss, shorter hospital stay, and improved
      postoperative quality of life. Intracorporeal urinary diversion is still in the
      experimental phase, and effort is needed to make it technically easier and widely
      accepted. CONCLUSIONS: With the worldwide rapid spread of robot-assisted
      surgeries, RARC is evolving as a reliable minimally invasive alternative to
      standard open surgery. Awaiting long term oncological results, adequately powered
      prospective randomized trials comparing open, laparoscopic and robotic approaches
      are urgently needed.

PMID- 20156381
TI  - Laparoscopic pyeloplasty versus robotic pyeloplasty for ureteropelvic junction
      obstruction: a series of 60 cases performed by a single surgeon.
AB  - PURPOSE: To compare operative parameters and outcomes in 30 cases of robotic
      pyeloplasty (RP) versus 30 cases of laparoscopic pyeloplasty (LP), performed by a
      single surgeon, for ureteropelvic junction (UPJ) obstruction. METHODS: Patients
      with primary UPJ obstruction were included in the study. The same surgeon (AKH)
      performed RP (usually using a transperitoneal Anderson-Hynes technique) on 30
      patients in Group I and employed LP on 30 patients in Group II, in a
      nonrandomized fashion. The patients were followed for 18 months postoperatively.
      Three robotic and one assistant port were required in Group I, and 3 or 4 ports
      were utilized in Group II. In Group I, 26 patients had antegrade double-J
      stenting, 1 patient had retrograde double-J stenting, and 3 patients had
      stentless RP. In Group II, 22 patients had antegrade double-J stenting and 8
      patients had retrograde double-J stenting. RESULTS: The mean total operating
      times were 98 minutes and 145 minutes, the mean estimated blood losses were 40 mL
      and 101 mL, and the mean hospital stays of the patients were 2 days and 3.5 days,
      for patients in Group I and Group II, respectively. These patients were followed
      up postoperatively for 18 months. They received a clinical examination, an
      ultrasound, and a diuretic renal dynamic scan. At 18 months, imaging studies
      found no obstructions in the patients in Group I and found an obstruction in only
      one patient in Group II. One patient in Group II required a repeat open
      pyeloplasty following failed endoscopic management. CONCLUSION: In this patient
      series, UPJ obstruction was managed effectively with either RP or LP, and
      outcomes were durable. Compared to pure LP, pure RP enabled the surgeon to
      achieve quicker dissection, reconstruction, and intracorporeal suturing with fine
      sutures and with antegrade double-J stenting. With RP, the operating time was
      decreased, and the procedure offered greater ergonomic convenience to the
      surgeon. Long term postoperative success, however, was equivalent on follow up in
      both patient groups.

PMID- 20156382
TI  - Wine and treatment of genitourinary disease: from antiquity to modern times.
AB  - OBJECTIVE: Wine is one of the oldest documented medicinal remedies, dating back
      thousands of years. We explore the medicinal uses of wine, with a focus on the
      treatment of genitourinary disease, beginning in ancient Egypt, India, and
      Israel, and then moving forward to include Greek, Roman, and Arabic medicine. Our
      review continues into the Middle Ages and renaissance, and finally evaluates the
      medicinal properties of wine as we understand them in our current scientific
      paradigm and its specific application to urology. METHODS: A review of the
      literature was completed, reviewing the medical theories and medicinal uses of
      wine from ancient civilization to the present. RESULTS: Wine has been used in the
      treatment of genitourinary disease for thousands of years. This agent has been
      employed by physicians in nearly all cultures and in all eras of medical history.
      Medical uses include, but are not limited to, appetite stimulant, anesthetic,
      tonic, antiseptic, vasodilator, diuretic, antibacterial agent, and diaphoretic.
      The physiologic properties and value of this ancient medicine continue to be
      studied today. CONCLUSIONS: The medicinal use of wine has common applications
      over thousands of years and multiple civilizations. The pharmacologic and
      physiologic properties of this agent continue to be studied and applied in the
      modern era and continue to be relevant in the field of urology.

PMID- 20156383
TI  - Two cases of delayed patency following "failed" epididymovasostomy and subsequent
      percutaneous epididymal sperm aspiration.
AB  - SUMMARY: We describe two patients who underwent bilateral epididymovasostomy and
      subsequent percutaneous epididymal sperm aspiration (PESA) because of persistent
      azoospermia, after which sperm returned to the ejaculates of both patients,
      resulting in an unexpected natural pregnancy in one of the couples. PATIENTS: Two
      men, Patient A (age 35 years) and Patient B (age 37 years), underwent vasectomy
      reversal 8 and 9 years following vasectomies, respectively. In both cases,
      bilateral epididymovasostomy was required due to epididymal obstruction. Semen
      analysis was performed at 3 month intervals following the procedure. Both
      patients underwent PESA, and one couple completed intracytoplasmic sperm
      injection (ICSI). FINDINGS: In Patient A, PESA and ICSI resulted in a dizygotic
      twin pregnancy, which was followed by an unexpected natural pregnancy 3 years
      after the epididymovasostomy. Semen analysis indicated late patency. This
      experience prompted us to advise Patient B to continue undergoing semen analyses
      every 3 months, even though PESA and ICSI treatment had been initiated. One year
      after the reconstructive procedure, and after PESA was performed, semen analysis
      indicated patency. This couple has stopped ICSI treatments and is now attempting
      a natural pregnancy. CONCLUSIONS: Epididymovasostomy may result in delayed
      patency and natural pregnancy, even after PESA has been performed. This finding
      should be taken into consideration by clinicians and by couples trying to
      conceive a child following "failed" epididymovasostomy and subsequent PESA.

PMID- 20156386
TI  - Forensic implications in self-insertion of urethral foreign bodies.
AB  - A 54-year-old Caucasian male presented to our emergency department because he had
      self inserted a transparent plastic and flexible tube into the urethral meatus,
      during erotic games. A plain pelvic x-ray film and an abdominal ultrasound were
      executed to determine the size, shape, orientation and location of the foreign
      body, and any eventually associated visceral injuries or complications. As
      results, a long tube of about 50 cm was described entering the urethra and
      reaching the bladder cavity in which the tube was folded and wrapped, in absence
      of any visceral complication. The patient underwent an urgent urethrocystoscopy
      resulting in the retrieval of both the two recognized foreign bodies by an
      endoscopic basket extraction. To complete the therapeutic approach, we focused
      also on the possible psychiatric implications of the self insertion of a foreign
      body into the urethra, and the initial evaluation reached the diagnosis of
      depression. The self introduction of a foreign body into the urinary tract
      represents an index of potentially harmful "self-destructive" behaviors. If the
      self destructive and/or suicidal ideations are not recognized in the clinical
      setting and the patient subsequently self inflicts an injury or commits suicide,
      the urologist may face legal problems related to the lack of diagnosis and
      treatment, potentially interpretable as a medical error, and thus as a reckless
      conduct.

PMID- 20156387
TI  - Ice pack induced scrotal skin necrosis following vasectomy.
AB  - Skin necrosis due to excessive ice pack application following vasectomy has not
      been previously reported. We report a rare case of postvasectomy skin necrosis
      resulting from extreme ice pack usage. This complication illustrates the
      importance of clear communication of postvasectomy instructions to patients. This
      complication was successfully managed with autolytic debridement without surgical
      debridement.

PMID- 20156388
TI  - Ureteric stricture secondary to unusual extension of prostatic adenocarcinoma.
AB  - This article describes an unusual finding in a patient who presented with an
      adenocarcinoma of the prostate and right hydronephrosis. A 68-year-old male
      presented with right hydronephrosis and a PSA of 96. DRE was consistent with cT3
      carcinoma. Cystoscopy showed an exophytic superficial transitional cell carcinoma
      (TCC) of the bladder and a transrectal biopsy of the prostate confirmed
      adenocarcinoma Gleason score 4+3. Staging investigations (CT pelvis and bone
      scan) were negative; androgen deprivation therapy was therefore initiated for the
      prostatic adenocarcinoma. Upper tract imaging showed multiple filling defects in
      the proximal ureter. Ureteroscopy showed a stricture at the level of the iliac
      vessels. With a working diagnosis of upper tract TCC, right open
      nephroureterectomy was performed. Final histology showed prostatic adenocarcinoma
      infiltrating the adventitia of the entire ureter up to the level of the renal
      pelvis. A rare cause of ureteric stricture, contiguous spread of prostatic
      adenocarcinoma, should be considered in the differential diagnosis of patients
      presenting with upper tract obstruction and a known history of prostatic
      adenocarcinoma. Androgen deprivation therapy for several months did not seem to
      cause resolution of the tumor in the periureteric, ureteric and perihilar
      tissues.

PMID- 20156389
TI  - Metastatic esophageal adenocarcinoma to the prostate presenting with bilateral
      ureteral obstruction.
AB  - Carcinoma metastatic to the prostate occurs rarely and is most commonly
      associated with malignant bladder neoplasms. We present the case of a 73-year-old
      male with a history of gastroesophageal adenocarcinoma and clinically symptomatic
      benign prostatic hyperplasia who underwent photoselective vaporization of the
      prostate and presented several months later with gross hematuria, intermittent
      urinary retention and bilateral ureteral obstruction causing acute renal failure.
      After relieving the ureteral obstruction, subsequent transurethral resection of
      the prostate revealed locally invasive metastatic esophageal adenocarcinoma. To
      our knowledge, this is the first reported case of metastatic gastroesophageal
      carcinoma to the prostate.

PMID- 20156390
TI  - Giant desmoid tumor in a case of ileal neobladder.
AB  - Aggressive fibromatosis or desmoid tumor, is a histologically benign entity with
      unknown etiology that may present a serious clinical course. Due to its high
      tendency to recur and local aggressive behavior and as there is no established
      effective medical treatment, complete surgical excision remains the sole
      management. To our knowledge, we describe the first case of giant desmoid tumor
      which arised from ileal neobladder mesenterium in a bladder cancer patient with
      orthotopic substitution.

PMID- 20156391
TI  - Urolith masquerading as severe acute radiation toxicity: case report.
AB  - INTRODUCTION: Postoperative radiotherapy after radical prostatectomy has been
      shown to improve numerous outcomes for selected patients in mature randomized
      controlled trials. During treatment patients usually experience mild to moderate
      urinary symptoms, lower gastrointestinal symptoms and tiredness. We describe an
      unusual case of a patient experiencing severe, culture negative urinary symptoms
      early in a course of salvage radiotherapy. MATERIALS AND METHODS: A patient's
      history was retrospectively derived from a single institution. RESULTS: A total
      radiation dosage of 66 Gy in 33 fractions was to be delivered to the prostate bed
      by intensity modulated radiation therapy. Urinary symptoms consisting of
      hematuria, dysuria and urination of cellular debris developed very early during
      the treatment, were not related to infection and were refractory to breaks from
      radiation therapy. Computed tomography imaging revealed a 3.5 cm diameter urolith
      in the posterior bladder. Urinary symptoms resolved after surgical management
      consisting of, cystolitholapaxy with laser cystoscopy. CONCLUSIONS: While rare,
      urolithiasis should be considered when severe, early, culture negative dysuria
      develops on radiotherapy for prostate cancer.

PMID- 20156392
TI  - An unusual clinical presentation of rhabdomyomatous Wilms' tumor.
AB  - Wilms' tumor (WT) is the most common primary malignant renal tumor in children
      and usually presents as an abdominal mass. Rhabdomyomatous nephroblastoma is a
      rare histologic variant of WT. Herein we report an unusual case of WT with
      rhabdomyomatous differentiation presenting with hematuria and the passage of
      tissue via the urethra in a 2-year-old male.

PMID- 20156393
TI  - Office based urology trials.

PMID- 20156394
TI  - Open clinical uro-oncology trials in Canada.

PMID- 20156395
TI  - Deviance as adherence to injunctive group norms: the overlooked role of social
      identification in deviance.
AB  - We currently report three studies investigating group members' expressions of
      dissatisfaction and discontent with the behaviour and attitudes of their in-group
      members. Our analysis examines the context in which group members will deviate
      from actual group member behaviour. We argue that highly identifying group
      members will challenge fellow group member behaviour when that group member
      behaviour is perceived to violate injunctive group norms. Further, we predicted
      that high identifiers would still challenge such group member behaviour even if
      that behaviour were conducted by a majority of group members. Thus, high
      identifiers were predicted to express descriptively deviant opinions when the
      behaviour of other members contravenes injunctive group norms. In Studies 1 and
      2, group-level self-definition served as a moderator in the relationship between
      the expression of discontent and perceived injunctive norm violation; in Study 3,
      group-level self-investment served as this moderator. The findings supported our
      predictions. This support was particularly strong when a majority of group
      members violated group norms. Implications for the analysis of the relationship
      between social identification and deviance are discussed.

PMID- 20156396
TI  - Physical activity and adolescents: an exploratory randomized controlled trial
      investigating the influence of affective and instrumental text messages.
AB  - OBJECTIVE: The present study attempts to develop and pilot the feasibility and
      efficacy of a novel intervention using affective messages as a strategy to
      increase physical activity (PA) levels in adolescents. Design An exploratory
      pilot randomized control trial was used to compare behaviour change over 2 weeks.
      A modified form of the International Physical Activity Questionnaire was used to
      assess PA behaviour. A total of 120 adolescents (16-19 years) from 4 sixth forms
      in West Yorkshire completed the field-based study. METHOD: Participants were
      randomly assigned to one of three experimental conditions, or the control
      condition (N=28). Participants in experimental conditions received 1 short
      messaging service (SMS) text message per day over the 2 weeks, which included
      manipulations of either affective beliefs (enjoyable/unenjoyable; N=31),
      instrumental beliefs (beneficial/harmful; N=30), or a combination of these
      (N=31). Control participants received one SMS text message per week. Outcomes
      were measured at baseline and at the end of the 2 week intervention. RESULTS: PA
      levels increased by the equivalent of 31.5  minutes of moderate (four metabolic
      equivalent) activity per week during the study. Main effects of condition
      (p=.049), and current physical activity level (p=.002) were identified, along
      with a significant interaction between condition and current activity level
      (p=.006). However, when the sample was split at baseline into active and inactive
      participants, a main effect of condition remained for inactive participants only
      (p=.001). Post hoc analysis revealed that inactive participants who received
      messages targeting affective beliefs increased their activity levels
      significantly more than the instrumental (p=.012), combined (p=.002), and control
      groups (p=.018). CONCLUSION: Strategies based on affective associations may be
      more effective for increasing PA levels in inactive individuals.

PMID- 20156397
TI  - [Anal fistulas--an unsolved clinical problem].

PMID- 20156398
TI  - [Treating high anal fistulae with slow cutting seton].
AB  - INTRODUCTION: The aim was to determine the incidence of anal incontinence,
      recurrence rate and patient satisfaction after using slow-cutting setons for
      transsphincteric anal fistula repair. MATERIAL AND METHODS: A retrospective study
      with prospective follow up in 58 patients who had undergone surgery for
      transsphincteric perianal fistulas with a slow-cutting seton. A total of 17
      patients were excluded or lost in the follow up period. A questionnaire was send
      to 41 cases to the severity of incontinence for gas, liquid and stool according
      to the Wexner-score. Recurrence rate, sick leave and satisfaction with the
      treatment were estimated. RESULTS: The questionnaire was returned from 34
      patients. In all 23 men and 11 women had the seton tightened for the first time
      after a mean period of 32 days. The mean number of tightenings was five (range: 2
      9). The mean duration of treatment was 256 days (range: 61-634). A total of four
      patients (12%) experienced recurrence. Twenty-one patients (61,7%) had a Wexner
      score of one or more. Eight patients (23,5%) scored more than four. A total of 28
      patients (82%) were 75-100% satisfied with the treatment. Two patients (6%) were
      absolutely dissatisfied, and were considered failures. We found no association
      between the reported satisfaction with the treatment and the degree of
      incontinence. CONCLUSION: Despite a very high level of satisfaction among the
      patients, the high rate of incontinence suggests that other non-invasive
      techniques should be used as first-line treatment of anal fistulas. In cases
      where multiple attempts at repair have failed, the slow-cutting seton may be the
      best option.

PMID- 20156399
TI  - [Epidemiology, morbidity and mortality for infants with a gestational age of 24
      31 weeks].
AB  - INTRODUCTION: To describe the epidemiology, in-hospital morbidity and mortality
      until discharge from hospital for infants born with gestational age (GA) 24-31
      weeks. MATERIAL AND METHODS: All newborns with GA 24-31 weeks, born in 2000-2005
      and with antenatal care in the former Vejle County were included. The study
      comprised two data sources. 1. "Neobase", a database comprising data on the
      treatment for all newborns admitted to the Neonatal Unit, 2. The Perinatal Audit
      for Vejle County - where all perinatal deaths are registered. RESULTS: A total of
      275 infants were born with GA 24-31 weeks, of whom 89 were born with GA < 24-27
      weeks. The prevalence of births at 24-31 weeks were 9.2 per 1,000 births and 3.0
      per 1.000 births with GA < 24-27 weeks. Thirty infants (11%) died before first
      discharge and for GA 24-27 weeks the mortality was 29%. Forty-six percent of all
      infant were from a pregnancy with more than one fetus. There was a significant
      increased risk of intraventricular haemorrhage of grade 2-4 for infants from
      multiple pregnancies (p < 0,05). Risk of birth before 32 weeks of gestation was
      20 times higher for infants from multiple pregnancies. Thirty-nine percent of all
      infants received treatment with surfactant. A significantly higher proportion of
      infants delivered by caesarean section received surfactant treatment compared to
      infants delivered vaginally (p < 0.001), even though median GA was higher (30 and
      29 weeks, respectively). CONCLUSION: A comparison with The Danish national study
      in infants with extremely low gestational age and birth weight from 1994-1995,
      reveals that the prevalence of births at 24-27 gestational weeks is stable or
      slightly increasing, while mortality has declined significantly. Almost half of
      all infants born before 32 weeks are from multiple pregnancies. Infants born by
      caesarean section more frequently received surfactant treatment.

PMID- 20156400
TI  - [Mallory-Weiss lesions].
AB  - INTRODUCTION: Mallory-Weiss syndrome (MW) has been know since 1929. Only few
      studies exist which focus on the prognosis of the lesion. No Danish MW data are
      available. The purpose of the study was to describe the demographics of patients
      admitted with an MW to a Danish surgical unit during a 5-year period and to
      investigate the prognosis of these patients. MATERIAL AND METHODS: Data from the
      patient records of 49 patients with endoscopically verified MW admitted through a
      five-year period were analysed. At follow-up, 35 patients were alive and
      contacted. A total of 29 responded. The mean time to follow-up from admittance
      was 42.7 months (range: 10.1-77.1). RESULTS: Haemostasis was achieved in all 49
      patients. Sixteen received active therapy during the endoscopic procedure.
      Haemoglobin at admittance was lower (p = 0.008), the presence of bleeding
      stigmata higher (p < 0.0001) and the number of patients receiving blood
      transfusion higher (p = 0.01) among those receiving active therapy than among the
      group receiving no therapy at the time of their endoscopy. At follow-up, 50% of
      those receiving active therapy were dead (eight of 16) compared with 18% (six of
      33) in the no-therapy group (p = 0.02). In the follow-up period, 10% of the
      patients admitted with an MW were re-admitted for a new gastrointestinal
      bleeding. CONCLUSION: Our data suggests that an attitude change is needed toward
      MW with bleeding stigmata. The course of the disease may not be as benign as
      generally believed. Further prospective studies designed to resolve this matter
      are needed.

PMID- 20156401
TI  - [Postpartum urinary retention].
AB  - Postpartum urinary retention occurs among 0.1-14.1% women after they have given
      birth. Different conditions during pregnancy and childbirth predispose to the
      condition, which may impair bladder emptying and cause late urological
      complications. Based on a review of literature published during the period 1980
      2008, we propose an algorithm for management of postpartum urinary retention.

PMID- 20156402
TI  - [Obesity: one of this century's greatest health challenge?].
AB  - The prevalence of overweight and obesity exceed 50% in many European countries.
      Obesity is responsible for 2-8% of all health costs and 10-13% of all deaths in
      Europe. Only a fraction of patients obtain a medically relevant weight loss of 5
      10% through lifestyle intervention. Surgery is limited to severe obesity and is
      very costly; therefore pharmaceuticals are a relevant alternative. Such treatment
      is hampered by the lack of official guidelines and a relatively limited effect
      compared to the expectations of patients as well as medical staff. Guidelines and
      official subsidies are debated.

PMID- 20156403
TI  - [Obesity is not associated with an increased mortality in critical disease and
      intensive care].
AB  - The prevalence of obesity is increasing. The mortality and morbidity among obese
      intensive care unit (ICU) patients has been a matter of concern. Most of the
      retrospective studies performed have yielded contradictory results. Recently, two
      large prospective studies showed that respiratory failure, length of mechanical
      ventilation and ICU acquired infections were increased in obese patients. Obesity
      was, however, not associated with increased mortality. The results were confirmed
      by a meta-analysis which showed that obesity was associated with increased
      morbidity but not with increased mortality.

PMID- 20156404
TI  - [Personality test and prediction of antidepressive treatment effect in mental
      illness].
AB  - INTRODUCTION: The STAR*D project showed that standard treatment of patients with
      major depression with citalopram resulted in a 36.8% remission in a group of
      patients. A switch to or supplementing with cognitive therapy substantially
      increased the remission rate. It would be desirable to identify in advance those
      patients in whom adjuvant therapy would be of a special benefit. MATERIAL AND
      METHODS: Answers to questions about personality traits (Temperament and Character
      Inventory (TCI)) were gathered from a mixed group of hospitalized and ambulant
      Danish psychiatric patients (n = 63) and matched with answers to questions on
      quality of life and degree of depression (Major Depression Inventory (MDI)). The
      hospitalized patients answered those questions again when discharged.
      Confirmatory factor analysis was used to evaluate the quality of the questions
      with regard to their information on latent categories and dimensions. RESULTS: A
      number of the questions were of low quality and could be omitted in this group of
      patients. The revised personality profile showed that patients with a higher
      score for harm avoidance also had a higher depression score measured at discharge
      from the hospital or during ambulant treatment. CONCLUSION: The TCI screening
      identifies a group of patients that have a high risk of getting a limited
      antidepressive treatment effect. An adjuvant intervention to the
      psychopharmacologic treatment could be offered, e.g. cognitive therapy.

PMID- 20156405
TI  - [Statin-induced dysphagia].
AB  - A 68-year-old man was referred with progressive dysphagia. During the course, the
      patient developed muscle fatigue and additional signs of myopathy such as high
      levels of creatine kinase. The dysphagia was a late-onset side-effect to the
      treatment with lipid-lowering drugs. Cessation of treatment gives quick remission
      of symptoms and normalization of creatine kinase. As an increasing number of
      patients are being treated with lipid-lowering drugs, it is important to recall
      that myopathy is a dangerous side-effect which may have either quick or delayed
      onset, and that dysphagia can be the initial symptom.

PMID- 20156406
TI  - [Actinomyces diagnosed after prolonged clinical investigation focused on cancer].
AB  - We describe a prolonged diagnostic process of 7 months before an infection with
      Actinomyces species could be diagnosed. Initially, a malignant tumour of the
      pelvic area was suspected. The patient underwent 3 CT-scans, 4 ultrasound scans
      and 5 biopsies before the diagnosis was suspected. Only the fourth
      microbiological investigation could confirm the diagnosis. This case emphasizes
      the necessity of microbiological examination of biopsies, when a tumour is found
      and malignancy cannot be confirmed, and is a reminder of Actinomyces species as
      an important pathogen in such cases.

PMID- 20156407
TI  - [Congenital aplasia of left-sided pericardium].
AB  - Congenital defects of the pericardium are very rare and are often not recognized
      before surgery. We report a case study of a 16-year-old girl with a four-year
      history of dyspnoea on exertion, palpitations, left sided thoracic pain and near
      syncope. Explorative thoracotomy revealed total absence of the left sided
      pericardium. This allows the heart to become displaced, thus giving the patient
      her uncharacteristic symptoms. The large defect was left open, to avoid
      compromising the venous circulation.

PMID- 20156408
TI  - [Tuberculosis caused by Mycobacterium africanum].
AB  - Tuberculosis (TB) is caused by pathogenic species within the Mycobacterium
      tuberculosis complex (MTBC). In the present case, a 40-year-old African man was
      admitted acutely. Despite negative microscopy, anti-TB treatment was initialized.
      Thirteen hours after hospitalisation, the patient suffered circulatory failure
      and died. Post mortem material from the lungs and pericardia tested positive for
      MTBC and was identified as Mycobacterium africanum by a new molecular method that
      enables identification of six of the eight MTBC species and provides clinicians
      with species-specific results.

PMID- 20156409
TI  - [Basal cell adenocarcinoma of the sublingual gland].
AB  - The cause of a swelling in the floor of the mouth will in most cases be benign.
      For example, a ranula, sialolithiasis and/or infection. Tumors of the sublingual
      gland are very rare, but 90% are malignant and therefore malignancy should always
      be excluded in case of an asymptomatic swelling covered by intact mucosa.

PMID- 20156411
TI  - Inflammatory biomarkers in 70 depressed inpatients with and without the metabolic
      syndrome.
AB  - OBJECTIVE: Chronic subclinical inflammation may be associated with the metabolic
      syndrome as well as with depression. We examined the impact of the metabolic
      syndrome on concentrations of inflammatory biomarkers in major depression.
      METHOD: Data for 70 inpatients with major depressive disorder (diagnosed
      according to ICD-10 and DSM-IV), and with or without the metabolic syndrome, were
      assessed 4 to 5 weeks after admission to the clinic of the Department of
      Psychiatry, Charite-University Medicine, Berlin, between 2005 and 2007. The
      metabolic syndrome was defined according to the criteria of the International
      Diabetes Federation (2005). Immunologic biomarkers assessed included adiponectin,
      resistin, serum amyloid A (SAA), C-reactive protein (CRP), fibrinogen,
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble E
      selectin, and CD40 ligand (CD40L). Severity of depression was measured with the
      17-item Hamilton Depression Rating Scale. RESULTS: After regressional correction
      for confounding variables and covariates, a 2-factorial analysis of variance
      (metabolic syndrome x time) revealed that the metabolic syndrome's presence
      affected adiponectin (F(43,1) = 5.56; P < .05) and IL-6 levels (F(25,1) = 6.80; P
      < .05) significantly. There was also a trend for effects on fibrinogen levels
      (F(47,1) = 3.66; P = .06). CONCLUSIONS: This is the first study to evaluate the
      putative additive effect of the metabolic syndrome on a panel of 9 inflammatory
      biomarkers in depression. Our findings support an additive effect on some
      (adiponectin, IL-6, and trendwise for fibrinogen) markers. Patients with the
      metabolic syndrome and major depression are at higher risk for more frequent and
      more severe cardiovascular side effects than their counterparts without the
      metabolic syndrome.

PMID- 20156410
TI  - Incidence of tardive dyskinesia with atypical versus conventional antipsychotic
      medications: a prospective cohort study.
AB  - OBJECTIVE: Most previous studies of the incidence of tardive dyskinesia with
      atypical antipsychotics compared with conventional antipsychotics have not had
      tardive dyskinesia as their primary focus. The current study aimed to compare the
      incidence of tardive dyskinesia with atypical vs conventional antipsychotics
      using methods similar to those from a previous prospective cohort study at our
      site in the 1980s. METHOD: Three hundred fifty-two initially tardive dyskinesia
      free psychiatric outpatients (diagnosed at baseline using the Structured Clinical
      Interview for DSM-IV) were examined for a new diagnosis of tardive dyskinesia
      (using the Abnormal Involuntary Movement Scale and Glazer-Morgenstern criteria)
      every 6 months for up to 4 years at a community mental health center. At
      baseline, subjects were receiving conventional antipsychotics only (23%),
      atypicals only (64%), or both (14%). Only 26 subjects had never received
      conventional antipsychotics. Baseline evaluations were conducted from November
      2000 through May 2003. Follow-ups were conducted through February 2005. RESULTS:
      Compared with subjects treated with conventional antipsychotics alone since the
      previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects
      treated with atypical antipsychotics alone was 0.68 (95% CI, 0.29-1.64). The
      incidence and prevalence of tardive dyskinesia was similar to previous findings
      at this site in the 1980s. CONCLUSIONS: The incidence of tardive dyskinesia with
      recent exposure to atypical antipsychotics alone was more similar to that for
      conventional antipsychotics than in most previous studies. Despite high
      penetration of atypical antipsychotics into clinical practice, the incidence and
      prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s.
      Clinicians should continue to monitor for tardive dyskinesia, and researchers
      should continue to pursue efforts to treat or prevent it.

PMID- 20156412
TI  - Type D personality predicts clinical events after myocardial infarction, above
      and beyond disease severity and depression.
AB  - OBJECTIVE: To investigate the effect of Type D personality (high negative
      affectivity and social inhibition) on cardiac death and/or recurrent myocardial
      infarction (MI) in patients with acute MI, after adjustment for disease severity
      and depression. To explore the differential effect of Type D on early (< or = 6
      months) versus late (> 6 months) events separately. METHOD: Patients hospitalized
      for acute MI (N = 473) were recruited between May 2003 and May 2006. Patients
      were assessed on demographic and clinical variables and completed the Type D
      Personality Scale within the first week of hospital admission for acute MI;
      depression severity was assessed with the 17-item Hamilton Depression Rating
      Scale. The mean follow-up period was 1.8 years. RESULTS: There were 44 events
      attributable to cardiac death (n = 16) or recurrent MI (n = 28), with 26 early
      and 18 late events. Type D patients were at cumulative increased risk of
      death/recurrent MI compared with non-Type D patients (16.3% vs 7.8%; P = .012).
      Cardiac history, left ventricular ejection fraction, and use of statins were
      predictors of total and late death/recurrent MI, with statins showing a
      substantial protective effect. In addition, cardiac history and use of statins
      were significantly associated with early death/recurrent MI. Type D patients had
      a 2-fold increased risk of total death/recurrent MI after adjustment for disease
      severity and depression (HR = 2.23; 95% CI, 1.14-4.35; P = .019) and a more than
      3-fold increased risk of late death/recurrent MI (HR = 3.57; 95% CI, 1.23-10.30;
      P = .019). CONCLUSIONS: Type D was a strong predictor of adverse cardiac outcome
      after acute MI, above and beyond disease severity and depression severity, and
      the associated risk was similar to that of traditional cardiovascular risk
      factors. Type D may be an important psychosocial factor to assess in patients
      post-MI for risk stratification purposes.

PMID- 20156413
TI  - Case reports of postmarketing adverse event experiences with olanzapine
      intramuscular treatment in patients with agitation.
AB  - OBJECTIVE: Agitation is a medical emergency with increased risk for poor outcome.
      Successful treatment often requires intramuscular (IM) psychotropics. Safety data
      from the first 21 months of olanzapine IM, approved in the United States for the
      treatment of agitation associated with schizophrenia and bipolar disorder, are
      presented. METHOD: A Lilly-maintained safety database was searched for all
      spontaneous adverse events (AEs) reported in temporal association with olanzapine
      IM treatment. RESULTS: The estimated worldwide patient exposure to olanzapine IM
      from January 1, 2004, through September 30, 2005, was 539,000; 160 cases
      containing AEs were reported from patients with schizophrenia (30%), bipolar
      disorder (21%), unspecified psychosis (10%), dementia (8%), and depression (5%).
      Many reported concomitant treatment with benzodiazepines (39%) or other
      antipsychotics (54%). The most frequently reported events involved the following
      organ systems: central nervous (21%), cardiac (12%), respiratory (6%), vascular
      (6%), and psychiatric (5%). Eighty-three cases were considered serious, including
      29 fatalities. In these fatalities, concomitant benzodiazepines or other
      antipsychotics were reported in 66% and 76% of cases, respectively. The most
      frequently reported events in the fatal cases involved the following organ
      systems: cardiovascular (41%), respiratory (21%), general (17%), and central
      nervous (10%). The majority of fatal cases (76%) included comorbid conditions and
      potentially clinically significant risk factors for AEs. CONCLUSIONS: Clinicians
      should use care when treating agitated patients, especially when they present
      with concurrent medical conditions and are treated with multiple medications,
      which may increase the risk of poor or even fatal outcomes. Clinicians should use
      caution when using olanzapine IM and parenteral benzodiazepines simultaneously.

PMID- 20156414
TI  - Extraction of RNA from fermented milk products for in situ gene expression
      analysis.
AB  - This work describes a simple method for extracting high-quality microbial RNA
      from fermented milk. Pretreatment consists merely of adding a concentrated
      solution of sodium citrate to the milk product. The proposed method provides
      consistently better yields of high-quality RNA than the conventional method
      independent of the texture of the fermented milk. Furthermore, it can be used
      with small amounts of starting material, requiring only the use of Eppendorf-size
      centrifuges-a great advantage for analytical laboratories. The RNA obtained is
      suitable for the detection of live microorganisms and for transcriptional studies
      based on quantitative reverse transcription polymerase chain reaction (RT-qPCR).

PMID- 20156415
TI  - Reversed-phase high-performance liquid chromatography method for simultaneous
      analysis of two liposome-formulated short interfering RNA duplexes.
AB  - Gene silencing induced by short interfering RNA (siRNA) has proven to be useful
      in genomic research and has great potential for therapeutic applications;
      however, siRNAs are not readily bioavailable. Cationic liposomes offer effective
      protection of drug product from nucleases and enable distribution to desired
      target organs. The amount of siRNA in the formulation must be determined
      accurately. We have developed a stability-indicating, ion-pair, reversed-phase
      high-performance liquid chromatography method to separate and accurately
      quantitate two siRNA duplexes in a liposome without sample pretreatment. The
      gradient mobile phase system consisted of 385mM hexafluoro-2-propanol, 14.5mM
      triethylamine, and 5% methanol (mobile phase A) and 385mM hexafluoro-2-propanol,
      14.5mM triethylamine, and 90% methanol (mobile phase B). The column used was an
      XBridge C18 column (50x2.1mm i.d., 2.5microm particle size), and separation was
      performed at 60 degrees C. Quantitation was achieved with ultraviolet (UV)
      detection at 260nm. Linearity was established for the single strands of both
      siRNA duplexes for concentrations ranging from 10 to 110microg/ml. Accuracy of
      the method was determined by replicate analysis (n=5) at four concentrations
      (R(2)>0.996 and relative standard deviations [RSDs] of 1-4%). The use of an ion
      pairing reagent that is compatible with mass spectrometry detection makes this
      method amenable to liquid chromatography-mass spectrometry (LC-MS) impurity
      profiling.

PMID- 20156416
TI  - Assessing the DNA methylation status of single cells with the comet assay.
AB  - The comet assay (single cell gel electrophoresis) is a cost-effective, sensitive,
      and simple technique that is traditionally used for analyzing and quantifying DNA
      damage in individual cells. The aim of this study was to determine whether the
      comet assay could be modified to detect changes in the levels of DNA methylation
      in single cells. We used the difference in methylation sensitivity of the
      isoschizomeric restriction endonucleases HpaII and MspI to demonstrate the
      feasibility of the comet assay to measure the global DNA methylation level of
      individual cells. The results were verified with the well-established cytosine
      extension assay. We were able to show variations in DNA methylation after
      treatment of cultured cells with 5-azacytidine and succinylacetone, an
      accumulating metabolite in human tyrosinemia type I.

PMID- 20156417
TI  - Detection of glycation sites in proteins by high-resolution mass spectrometry
      combined with isotopic labeling.
AB  - The products of nonenzymatic glycation of proteins are formed in a chemical
      reaction between reducing sugars and the free amino group located either at the N
      terminus of the polypeptide chain or in the lysine side chain. Glycated proteins
      and their fragments could be used as markers of the aging process as well as
      diabetes mellitus and Alzheimer's disease, making them an object of interest in
      clinical chemistry. In this article, we propose a new method for the
      identification of peptide-derived Amadori products in the mixtures obtained by
      enzymatic hydrolysis of glycated proteins. Two proteins, ubiquitin and human
      serum albumin (HSA), were modified with an equimolar mixture of glucose and
      [(13)C(6)]glucose and were subjected to enzymatic hydrolysis. The obtained
      enzymatic digests were analyzed by high-resolution mass spectrometry (HRMS), and
      the peptide-derived Amadori products were identified on the basis of specific
      isotopic patterns resulting from (13)C substitution. The number of glycated
      peptides in the digest of HSA detected by our procedure was in agreement with the
      data recently reported in the literature.

PMID- 20156418
TI  - Fluorescein-labeled glutathione to study protein S-glutathionylation.
AB  - Numerous studies of S-glutathionylation of cysteine thiols indicate that this
      protein modification plays a key role in redox regulation of proteins. To
      facilitate the study of protein S-glutathionylation, we developed a synthesis and
      purification to produce milligram quantities of fluorescein-labeled glutathione.
      The amino terminus of the glutathione tripeptide reacted with fluorescein
      isothiocyanate readily in ammonium bicarbonate. Purification by solid phase
      extraction on C8 and C18 columns separated excess reactants from desired
      products. Both oxidized and reduced fluorescein-labeled glutathione reacted with
      a variety of thiol-containing proteins to yield fluorescent proteins.

PMID- 20156419
TI  - DNA binding and aggregation by carbon nanoparticles.
AB  - Significant environmental and health risks due to the increasing applications of
      engineered nanoparticles in medical and industrial activities have been concerned
      by many communities. The interactions between nanomaterials and genomes have been
      poorly studied so far. This study examined interactions of DNA with carbon
      nanoparticles (CNP) using atomic force microscopy (AFM). We experimentally
      assessed how CNP affect DNA molecule and bacterial growth of Escherichia coli. We
      found that CNP were bound to the DNA molecules during the DNA replication in
      vivo. The results revealed that the interaction of DNA with CNP resulted in DNA
      molecule binding and aggregation both in vivo and in vitro in a dose-dependent
      manner, and consequently inhabiting the E. coli growth. While this was a
      preliminary study, our results showed that this nanoparticle may have a
      significant impact on genomic activities.

PMID- 20156420
TI  - Aluminum chloride induced oxidative damage on cells derived from hippocampus and
      cortex of ICR mice.
AB  - Aluminum (Al) is among the most abundant elements on earth, it has been
      associated with the etiology of Alzheimer's disease. In the present study,
      AlCl(3) was administered with the dose of 10, 50 or 300 mg/kg b.wt/day through
      diet for 100 days. On day 101, overnight-fasted animals were sacrificed, the
      whole brains were removed and the cells from hippocampus or cortex were separated
      for the measurements: malondialdehyde (MDA), superoxide dismutase (SOD), nuclear
      DNA (nDNA) and mitochondrial DNA (mtDNA) damage. AlCl(3) exposure resulted in
      increased MDA levels accompanied by decreased activities of SOD in the cells.
      Comet assay demonstrated that aluminum induces nDNA damage in a dose-dependent
      manner, dramatically increased formation of 8-hydroxy 2-deoxyguanosine (8-OHdG)
      in the mtDNA isolated from the cells was also measured. The alterations seem more
      serious than the results displayed by the studies performed with lower doses of
      aluminum. However, a detailed biochemical mechanism by which aluminum accelerates
      mtDNA damage has not yet been identified, but the decrease in superoxide
      dismutase (SOD) activity and increase in MDA level in aluminum-treated mice may
      suggest the involvement of oxidative stress.

PMID- 20156421
TI  - Decreased serotonin levels associated with behavioral disinhibition in tissue
      plasminogen activator deficient (tPA-/-) mice.
AB  - Tissue Plasminogen Activator (tPA) is a serine protease expressed in different
      areas of the mammalian brain. It has been used clinically to dissolve clots and
      shown to have a role in neurodegeneration. Early studies suggested that tPA plays
      an important role in the processes of learning and memory, demonstrated at the
      level of behavior and synaptic plasticity. Herein, we extend the behavioral
      characterization of these mice to the related dimension of exploratory-related
      behavior using an extensive battery of behavioral tests as well as the
      neurotransmitter metabolism associated with the behavioral measures. Our results
      indicate a behavior tendency in these mice consistent with "impulsivity" or
      reduced exploratory inhibition. These patterns are accompanied by decreased
      levels of serotonin in several brain regions important in behavioral regulation
      in the tPA(-/-) mice compared to control animals. Systemic administration of
      fluoxetine reversed the behavioral disinhibition of tPA(-/-) mice, further
      supporting an important alteration in behavior regulation mediated by serotonin
      systems as underappreciated but important element of the behavioral phenotype of
      these animals.

PMID- 20156422
TI  - Nutritional status alters saccharin intake and sweet receptor mRNA expression in
      rat taste buds.
AB  - Sweet taste usually signifies the presence of caloric food. It is commonly
      accepted that a close association exists among sweet taste perception,
      preference, and nutritional status. However, the mechanisms involved remain
      unknown. To investigate whether nutritional status affects the preference for
      palatable solutions and alters sweet taste receptor gene expression in rats, we
      measured saccharin intake and preference using a two-bottle preference test, and
      changes in body weight, plasma leptin levels, and gene expression for the sweet
      taste receptor in taste buds in high-fat diet-induced obese rats and chronically
      diet-restricted rats. We found that the consumption and preference ratios for
      0.01 and 0.04 M saccharin were significantly lower in the high-fat diet-induced
      obese rats than in the normal diet rats, while the serum leptin levels were
      markedly increased in obese rats. Consistent with the changes in saccharin
      intake, the gene expression level of the sweet taste receptor T1R3 was
      significantly decreased in the high-fat diet-induced obese rats compared with the
      control rats. By contrast, the chronically diet-restricted rats showed remarkably
      enhanced consumption and preference for 0.04 M saccharin. The serum leptin
      concentration was decreased, and the gene expression of the leptin receptor was
      markedly increased in the taste buds. In conclusion, our results suggest that
      nutritional status alters saccharin preference and the expression of T1R3 in
      taste buds. These processes may be involved in the mechanisms underlying the
      modulation of peripheral sweet taste sensitivity, in which leptin plays a role.

PMID- 20156423
TI  - Expression of aquaporins 1 and 4 in the brain of spontaneously hypertensive rats.
AB  - Aquaporins (AQP) 1 and 4 are water channel proteins localized respectively at the
      level of the blood-cerebrospinal fluids (CSF) and blood brain (BBB) barriers.
      These barriers represent the sites of exchange between blood and nervous tissue
      and between blood, choroid plexus and CSF in brain ventricles respectively.
      Damage of these barriers may alter transfer of substances between blood and
      nervous tissue. In spontaneously hypertensive rats (SHR) chronic hypertension may
      induce BBB dysfunction and pronounced defects in the integrity of the blood-CSF
      barrier. AQP1 is expressed in the apical membrane of choroid plexus epithelium.
      AQP4 is expressed by astrocyte foot processes near blood vessels. The present
      study has assessed the expression of AQP1 and AQP4 in the brain of SHR in pre
      hypertensive (2 months of age), developing hypertension (4 months of age) and
      established hypertension (6 months of age) stages. Age-matched Wistar-Kyoto (WKY)
      rats were used as normotensive reference group. AQP1 expression is increased in
      choroid plexus epithelium of 6-month-old SHR. An increased expression of AQP4 was
      found in frontal cortex, striatum, and hippocampus of 4- and 6-month-old SHR
      compared to younger cohorts and age-matched WKY rats. These findings suggest that
      the increase in AQP expression may alter fluid exchange in BBB and/or in blood
      CSF barrier. This situation in case of an acute or excessively elevated rise of
      blood pressure can promote BBB changes causing the brain damage occurring in this
      animal model of hypertension.

PMID- 20156424
TI  - Microglia activation in the hypothalamic PVN following myocardial infarction.
AB  - Following a myocardial infarction (MI), inflammatory cytokines are elevated in
      the brain, as well as in plasma, indicating that inflammation is occurring in the
      brain in addition to the periphery. Microglia are the immune cells in the central
      nervous system and can produce cytokines when they are activated by an insult or
      injury. In the present study, we investigated whether MI in rats induces
      activation of microglia in the brain. We used immunohistochemistry to detect
      CD11b (clone OX-42) and morphological changes to identify activated microglia.
      Compared to control rats that had undergone sham surgical procedures, there was a
      significant increase in activated microglia in the hypothalamic paraventricular
      nucleus (PVN) following myocardial infarction. Activated microglia were not
      observed in the ventral hypothalamus, adjacent to the PVN, nor in the cortex,
      indicating the response was not the result of a generalized inflammatory reaction
      in the brain. Echocardiography and haemodynamic parameters after myocardial
      infarction indicated that reduced left ventricular function but congestive heart
      failure had not developed. In conclusion, microglia are activated in the PVN but
      not in the adjacent hypothalamus following myocardial infarction. The activated
      microglia may contribute to the increased local production of pro-inflammatory
      cytokines observed in the PVN after myocardial infarction and resulting in
      reduced left ventricular function.

PMID- 20156425
TI  - Inactivation or inhibition of neuronal activity in the medial prefrontal cortex
      largely reduces pup retrieval and grouping in maternal rats.
AB  - Previous research suggests that the maternal medial prefrontal cortex (mPFC) may
      play a role in maternal care and that cocaine sensitization before pregnancy can
      affect neuronal activity within this region. The present work was carried out to
      test whether the mPFC does actually play a role in the expression of maternal
      behaviors in the rats and to understand what specific behaviors this cortical
      area may modulate. In the first experiment, tetrodotoxin (TTX) was used to
      chemically inactivate the mPFC during tests for maternal behavior latencies.
      Lactating rats were tested on postpartum days 7-9. The results of this first
      experiment indicate that there is a large effect of TTX-induced inactivation on
      retrieval behavior latencies. TTX nearly abolished the expression of maternal
      retrieval of pups without significantly impairing locomotor activity. In the
      second experiment, GABA-mediated inhibition was used to test maternal behavior
      latencies and durations of maternal and other behaviors in postpartum dams. In
      agreement with experiment 1, it was observed that dams capable of retrieving are
      rendered incapable by inhibition in the mPFC. GABA-mediated inhibition in the
      mPFC largely reduced retrieval without altering other indices of maternal care
      and non-specific behavior such as ambulation time, self-grooming, and inactivity.
      Moreover, in both experiments, dams were able to establish contact with pups
      within seconds. The overall results indicate that the mPFC may play an active
      role in modulating maternal care, particularly retrieval behavior. External
      factors that affect the function of the frontal cortical site may result in
      significant impairments in maternal goal-directed behavior as reported in our
      earlier work.

PMID- 20156426
TI  - The effects of polyamine agonists and antagonists on N-methyl-D-aspartate-induced
      depolarizations of amphibian motoneurons in situ.
AB  - Polyamines have been found to reduce proton inhibition of isolated N-methyl-D
      aspartate (NMDA) channels recorded in vitro. This study examines the role of
      polyamine modulation of motoneuronal excitation in situ, with an emphasis on
      possible interactions with NMDA-mediated depolarization of motoneurons and
      receptor mediated modulation of NMDA receptors by L-glutamate and serotonin (5
      HT). Motoneuron membrane potential changes were electrotonically recorded in situ
      from the ventral root of isolated, hemisected amphibian spinal cords using
      sucrose gap techniques. The methods provided highly stable recordings (<1.0%) of
      membrane potential changes upon application of NMDA. Spermine, but not
      spermidine, enhanced NMDA-induced depolarization of motoneurons with and without
      Mg(2+) present in the superfusate but had no significant effect on either (1S,3R)
      1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, an mGLU receptor agonist) or 5
      HT2B-G-protein receptor mediated enhancement of Mg(2+) blocked NMDA-induced
      activity. The polyamine antagonist arcaine or the allosteric modulator ifenprodil
      had no effect on NMDA-induced changes in motoneuron membrane potentials recorded
      in situ but blocked the effects of spermine. Synthalin did not block spermine
      enhancement of NMDA-induced depolarization of motoneurons but mimicked Mg(2+)
      block of the NMDA channel. The data provide evidence that the proton block of the
      NMDA receptor is maximized in frog motoneurons in situ and also for a spermine
      specific polyamine site on native NMDA receptors of motoneurons that can enhance
      NMDA-induced depolarization when activated. Polyamines do not appear to be
      constitutively active at the motoneurons recorded since polyamine antagonists had
      no effect on either membrane depolarization or modulation of NMDA receptors.

PMID- 20156427
TI  - Stimulatory effects of Cuminum cyminum and flavonoid glycoside on Cyclosporine-A
      and restraint stress induced immune-suppression in Swiss albino mice.
AB  - Many herbs and spices are known to modulate the immune system and have been shown
      to restore the immunity in immuno-compromised individuals. Spices generally used
      to increase the taste and flavor of food also has the history of usage as an
      ayurvedic medicine. Therefore to explore the health modulating effects of Cuminum
      cyminum and to identify the active compound, immunomodulatory properties were
      evaluated using flowcytometry and ELISA in normal and immune-suppressed animals.
      C. cyminum and compound 1 stimulated the T cells and Th1 cytokines expression in
      normal animals. Swiss albino mice subjected to Cyclosporine-A induced immune
      suppression were dosed orally with C. cyminum (25, 50, 100 and 200 mg/kg) on
      consecutive days. The results showed that administration significantly increased
      T cells (CD4 and CD8) count and Th1 predominant immune response in a dose
      dependent manner thereby suggesting immunomodulatory activity through modulation
      of T lymphocytes expression. In restraint stress induced immune-suppressed
      animals, compound 1 countered the depleted T lymphocytes, decreased the elevated
      corticosterone levels and size of adrenal glands and increased the weight of
      thymus and spleen. Based on the data we may conclude that C. cyminum is a potent
      immunomodulator and may develop as a lead to recover the immunity of immuno
      compromised individuals.

PMID- 20156428
TI  - Reaction profiles of the interaction between sarin and acetylcholinesterase and
      the S203C mutant: model nucleophiles and QM/MM potential energy surfaces.
AB  - The phosphonylation mechanism of AChE and the S203C mutation by sarin (GB) is
      evaluated using two reaction schemes: a small model nucleophile (ethoxide,
      CH(3)CH(2)O(-)) and quantum mechanical/molecular mechanical (QM/MM) simulations.
      Calculations utilizing small model nucleophiles indicate that the reaction
      barrier for addition to GB is the rate-limiting step for both ethoxide and ethyl
      thiolate (CH(3)CH(2)S(-)); moreover, the activation barrier for addition to the
      phosphorus center of GB by ethyl thiolate is significantly larger (13.2 kcal/mol)
      than for ethoxide (8.3 kcal/mol). The decomposition transition state for both
      nucleophiles was determined to be approximately 1 kcal/mol. QM/MM simulations for
      AChE suggest a similar reaction mechanism for phosphonylation of the catalytic
      S203; however, the relative energetics are altered significantly compared to the
      isolated system. QM/MM results indicate that formation of the penta-coordinate
      intermediate is the rate-limiting step in the enzymatic system, with an
      activation barrier of 3.6 kcal/mol. Hydrogen-bonding interactions between the
      fluoride leaving group of GB with Y124 in AChE are observed throughout the
      reaction profile. The S203C mutation alters the relative energetics of the
      reaction, increasing the energy barrier for formation of the penta-coordinate
      intermediate to a value of 4.5 kcal/mol; moreover, the penta-coordinate
      intermediate (as product) is stabilized by an additional 6 kcal/mol when compared
      to wild-type AChE.

PMID- 20156429
TI  - ATP sensitizes H460 lung carcinoma cells to cisplatin-induced apoptosis.
AB  - Platinum resistance of cancer cells may evolve due to a decrease in intracellular
      drug accumulation, decreased cell permeability or by an increased deactivation of
      the drug by glutathione (GSH). The aim of this study was (1) to investigate the
      effect of adenosine 5'-triphosphate (ATP) on the cytotoxicity of cisplatin in a
      large cell lung carcinoma cell line (H460), and (2) to examine the potential
      involvement of increased cisplatin uptake, GSH depletion and pyrimidine
      starvation by ATP in this effect. H460 cells were harvested and seeded (5% CO(2);
      37 degrees C). Subsequently, cells were incubated with medium or ATP followed by
      an incubation with cisplatin. Cytotoxicity screening was analyzed by the
      sulforhodamine B (SRB) colorimetric assay, lactate dehydrogenase and caspase-3/7
      activity. Pre-incubation for 72h with 0.3 and 3mM ATP strongly enhanced the anti
      proliferative potency of cisplatin 2.9- and 7.6-fold, respectively. Moreover,
      after incubation of H460 cells with 0.3mM ATP the intracellular platinum
      concentration increased, indicating increased cisplatin uptake by ATP. ATP,
      despite lowering the LD(50) of cisplatin, did not modulate GSH levels in H460
      cells. ATP itself showed a biphasic effect on H460 cell growth: 0.3mM inhibited
      H460 cell growth via the pyrimidine starvation effect, activation of caspase-3/7
      and LDH leakage, while 3mM ATP showed no effect on cell growth. In conclusion,
      ATP sensitizes the H460 cells to cisplatin-induced apoptosis. The effect of 0.3mM
      ATP is not due to GSH depletion but involves increased cisplatin uptake and
      pyrimidine starvation due to ATP conversion to adenosine followed by cellular
      uptake.

PMID- 20156430
TI  - Pro-2-PAM therapy for central and peripheral cholinesterases.
AB  - Novel therapeutics to overcome the toxic effects of organophosphorus (OP)
      chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980
      1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP
      exposure therapy in the United States consists of atropine sulfate (to block
      muscarinic receptors), the acetylcholinesterase (AChE) reactivator (oxime)
      pralidoxime chloride (2-PAM), and a benzodiazepine anticonvulsant to ameliorate
      seizures. A major disadvantage is that quaternary nitrogen charged oximes,
      including 2-PAM, do not cross the blood brain barrier (BBB) to treat brain AChE.
      Therefore, we have synthesized and evaluated pro-2-PAM (a lipid permeable 2-PAM
      derivative) that can enter the brain and reactivate CNS AChE, preventing seizures
      in guinea pigs after exposure to OPs. The protective effects of the pro-2-PAM
      after OP exposure were shown using (a) surgically implanted radiotelemetry probes
      for electroencephalogram (EEG), (b) neurohistopathology of brain, (c)
      cholinesterase activities in the PNS and CNS, and (d) survivability. The PNS
      oxime 2-PAM was ineffective at reducing seizures/status epilepticus (SE) in
      diisopropylfluorophosphate (DFP)-exposed animals. In contrast, pro-2-PAM
      significantly suppressed and then eliminated seizure activity. In OP-exposed
      guinea pigs, there was a significant reduction in neurological damage with pro-2
      PAM but not 2-PAM. Distinct regional areas of the brains showed significantly
      higher AChE activity 1.5h after OP exposure in pro-2-PAM treated animals compared
      to the 2-PAM treated ones. However, blood and diaphragm showed similar AChE
      activities in animals treated with either oxime, as both 2-PAM and pro-2-PAM are
      PNS active oximes. In conclusion, pro-2-PAM can cross the BBB, is rapidly
      metabolized inside the brain to 2-PAM, and protects against OP-induced SE through
      restoration of brain AChE activity. Pro-2-PAM represents the first non-invasive
      means of administering a CNS therapeutic for the deleterious effects of OP
      poisoning by reactivating CNS AChE.

PMID- 20156431
TI  - Evaluation of a technique to identify acetylcholinesterase C-terminal peptides in
      human serum samples.
AB  - A novel theory for neurodegeneration is that non-cholinergic functions of
      acetylcholinesterase (AChE) are responsible for the progressive death of global
      neurons. The C-terminal region of AChE has been shown to be responsible for non
      cholinergic actions of AChE by binding to an allosteric site on the alpha 7
      nicotinic acetylcholine receptor, thereby causing calcium influx; the resultant
      signal has trophic effects in immature neurons, but toxic effects in mature
      neurons. Although there is strong in vitro and in vivo evidence for the
      involvement of this C-terminal region of AChE in neurodegeneration, a cleaved C
      terminal peptide has not yet been identified in human brains. This preliminary
      study aimed to identify the cleaved AChE C-terminal peptide in serum from human
      Alzheimer's disease patients using immunoaffinity purification. A number of
      antibodies were tested for sensitivity and specificity towards peptide sequences
      from the C-terminus. Although the antibodies were able to identify peptide in
      vitro, peptide was not detected using immunoaffinity purification of human serum,
      possibly due to insufficient detection limits of the antibody. Therefore more
      sensitive techniques are required to identify cleaved AChE C-terminal peptides in
      human samples. None the less, C-terminal AChE peptide might act as a signalling
      molecule in an as yet unexplored system.

PMID- 20156432
TI  - Mechanisms for perivascular adipose tissue-mediated potentiation of vascular
      contraction to perivascular neuronal stimulation: the role of adipocyte-derived
      angiotensin II.
AB  - In rat mesenteric arteries we have recently found that perivascular adipose
      tissue (PVAT) promoted vasoconstriction to perivascular neuronal activation (by
      electrical field stimulation, EFS) through generation of superoxide. In this
      study, we examined the role of adipocyte-generated angiotensin II in PVAT
      mediated potentiation of contraction to nerve stimulation. In rat mesenteric
      PVAT, the presence of angiotesinogen and angiotensin I-converting enzyme (ACE)
      mRNA was confirmed by RT-PCR. Immunohistochemical staining showed the presence of
      angiotensin II in mesenteric PVAT. In rat mesenteric arteries, treatment of the
      vessels with an ACE inhibitor (enalaprilat) or angiotensin II type 1 receptor
      antagonist (candesartan) reduced PVAT-mediated potentiation of EFS-induced
      contraction. Exogenously applied angiotensin II enhanced EFS-induced contraction
      in arteries without PVAT, but not in the arteries with intact PVAT. Chronic
      treatment with an ACE inhibitor quinapril (14 days) lowered blood pressure and
      alleviated the potentiation effects of PVAT in EFS-induced contraction.
      Mesenteric arteries from quinapril-treated group now exhibited the potentiation
      response to exogenously applied angiotensin II in arteries with intact PVAT to a
      comparable level as in arteries with PVAT removed. Treatment with hydralazine
      reduced blood pressure to the same level as quinapril treatment, but did not
      affect PVAT-associated potentiation of vasoconstriction to EFS and the response
      to exogenously applied angiotensin II in PVAT-intact arteries. These results
      showed that adipocyte-derived angiotensin II is critically involved in PVAT
      mediated potentiation of EFS-evoked contraction in rat mesenteric arteries.

PMID- 20156433
TI  - Alpha-actinin 1 and alpha-actinin 4: contrasting roles in the survival, motility,
      and RhoA signaling of astrocytoma cells.
AB  - Alpha-actinin is a prominent actin filament associated protein for which
      different isoforms exist. Here, we have examined whether the two highly
      homologous non-muscle alpha-actinin isoforms 1 and 4 exhibit functional
      differences in astrocytoma cells. The protein levels of these isoforms were
      differentially regulated during the development and progression of astrocytomas,
      as alpha-actinin 1 was higher in astrocytomas compared to normal brains whereas
      alpha-actinin 4 was elevated in high-grade astrocytomas compared to normal brains
      and low grade astrocytomas. RNAi demonstrated contrasted contributions of alpha
      actinin 1 and 4 to the malignant behavior of U-373, U-87 and A172 astrocytoma
      cells. While alpha-actinin 1 appeared to favor the expansion of U-373, U-87 and
      A172 astrocytoma cell populations, alpha-actinin 4 played this role only for U
      373 cells. On the other hand, downregulation of alpha-actinin 4, but not 1,
      reduced cell motility, adhesion, cortical actin, and RhoA levels. Finally, in the
      three astrocytoma cell lines examined, alpha-actinin 1 and 4 had contrasted
      biochemical properties as alpha-actinin 4 was significantly more abundant in the
      actin cytoskeleton than alpha-actinin 1. Collectively, these findings suggest
      that alpha-actinin 1 and 4 are differentially regulated during the development
      and progression of astrocytomas because each of these isoforms uniquely
      contributes to distinct malignant properties of astrocytoma cells.

PMID- 20156434
TI  - Retention of prolyl hydroxylase PHD2 in the cytoplasm prevents PHD2-induced
      anchorage-independent carcinoma cell growth.
AB  - Cellular oxygen tension is sensed by a family of prolyl hydroxylases (PHD1-3)
      that regulate the degradation of hypoxia-inducible factors (HIF-1alpha and 
      2alpha). The PHD2 isoform is considered as the main downregulator of HIF in
      normoxia. Our previous results have shown that nuclear translocation of PHD2
      associates with poorly differentiated tumor phenotype implying that nuclear PHD2
      expression is advantageous for tumor growth. Here we show that a pool of PHD2 is
      shuttled between the nucleus and the cytoplasm. In line with this, accumulation
      of wild type PHD2 in the nucleus was detected in human colon adenocarcinomas and
      in cultured carcinoma cells. The PHD2 isoforms showing high nuclear expression
      increased anchorage-independent carcinoma cell growth. However, retention of PHD2
      in the cytoplasm inhibited the anchorage-independent cell growth. A region that
      inhibits the nuclear localization of PHD2 was identified and the deletion of the
      region promoted anchorage-independent growth of carcinoma cells. Finally, the
      cytoplasmic PHD2, as compared with the nuclear PHD2, less efficiently
      downregulated HIF expression. Forced HIF-1alpha or -2alpha expression decreased
      and attenuation of HIF expression increased the anchorage-independent cell
      growth. However, hydroxylase-inactivating mutations in PHD2 had no effect on cell
      growth. The data imply that nuclear PHD2 localization promotes malignant cancer
      phenotype.

PMID- 20156435
TI  - Micropatterned matrix directs differentiation of human mesenchymal stem cells
      towards myocardial lineage.
AB  - Stem cell response can be influenced by a multitude of chemical, topological and
      mechanical physiochemical cues. While extensive studies have been focused on the
      use of soluble factors to direct stem cell differentiation, there are growing
      evidences illustrating the potential to modulate stem cell differentiation via
      precise engineering of cell shape. Fibronectin were printed on poly(lactic-co
      glycolic acid) (PLGA) thin film forming spatially defined geometries as a means
      to control the morphology of bone marrow derived human mesenchymal stem cells
      (hMSCs). hMSCs that were cultured on unpatterned substrata adhered and flattened
      extensively (approximately 10,000 microm(2)) while cells grown on 20 microm
      micropatterend wide adhesive strips were highly elongated with much smaller area
      coverage of approximately 2000 microm(2). Gene expression analysis revealed up
      regulation of several hallmark markers associated to neurogenesis and myogenesis
      for cells that were highly elongated while osteogenic markers were specifically
      down-regulated or remained at its nominal level. Even though there is clearly
      upregulated levels of both neuronal and myogenic lineages but at the functionally
      relevant level of protein expression, the myogenic lineage is dominant within the
      time scale studied as determined by the exclusive expression of cardiac myosin
      heavy chain for the micropatterned cells. Enforced cell shape distortion
      resulting in large scale rearrangement of cytoskeletal network and altered
      nucleus shape has been proposed as a physical impetus by which mechanical
      deformation is translated into biochemical response. These results demonstrated
      for the first time that cellular shape modulation in the absence of any induction
      factors may be a viable strategy to coax lineage-specific differentiation of stem
      cells.

PMID- 20156437
TI  - Omentum-derived stromal cells improve myocardial regeneration in pig post
      infarcted heart through a potent paracrine mechanism.
AB  - Cell-based therapy could be a valid option to treat myocardial infarct (MI).
      Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative
      potential including cardiomyogenesis. Omentum is an extremely rich source of
      visceral fat and its accumulation seems to correlate with cardiovascular
      diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs)
      to affect heart function upon acute infarct in pigs induced by permanent ligation
      of the anterior interventricular artery (IVA). We demonstrated for the first time
      that the local injection of 50x10(6) of FOStCs ameliorates the functional
      parameters of post-infarct heart. Most importantly, histology of FOStCs treated
      hearts demonstrated a substantial improvement of cardiomyogenesis. In culture,
      FOStCs produced an impressive number and amount of angiogenic factors and
      cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in
      vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis
      and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs
      in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude
      that FOStCs efficacy was presumably mediated by a potent paracrine mechanism
      involving molecules that concomitantly improved angiogenesis, reduced
      inflammation and prevented cardiomyocytes death. Our results highlight for the
      first time the important role that human FOStCs may have in cardiac regeneration.

PMID- 20156436
TI  - Hypoglycosylated E-cadherin promotes the assembly of tight junctions through the
      recruitment of PP2A to adherens junctions.
AB  - Epithelial cell-cell adhesion is controlled by multiprotein complexes that
      include E-cadherin-mediated adherens junctions (AJs) and ZO-1-containing tight
      junctions (TJs). Previously, we reported that reduction of E-cadherin N
      glycosylation in normal and cancer cells promoted stabilization of AJs through
      changes in the composition and cytoskeletal association of E-cadherin scaffolds.
      Here, we show that enhanced interaction of hypoglycosylated E-cadherin-containing
      AJs with protein phosphatase 2A (PP2A) represents a mechanism for promoting TJ
      assembly. In MDCK cells, attenuation of cellular N-glycosylation with siRNA to
      DPAGT1, the first gene in the N-glycosylation pathway, reduced N-glycosylation of
      surface E-cadherin and resulted in increased recruitment of stabilizing proteins
      gamma-catenin, alpha-catenin, vinculin and PP2A to AJs. Greater association of
      PP2A with AJs correlated with diminished binding of PP2A to ZO-1 and claudin-1
      and with increased pools of serine-phosphorylated ZO-1 and claudin-1. More ZO-1
      was found in complexes with occludin and claudin-1, and this corresponded to
      enhanced transepithelial resistance (TER), indicating physiological assembly of
      TJs. Similar maturation of AJs and TJs was detected after transfection of MDCK
      cells with the hypoglycosylated E-cadherin variant, V13. Our data indicate that E
      cadherin N-glycans coordinate the maturity of AJs with the assembly of TJs by
      affecting the association of PP2A with these junctional complexes.

PMID- 20156438
TI  - The interfacial viscoelastic properties and structures of human and animal
      Meibomian lipids.
AB  - As the interface between the aqueous layer of the tear film and air, the lipid
      layer plays a large role in maintaining tear film stability. Meibomian lipids are
      the primary component of the lipid layer; therefore the physical properties of
      these materials may be particularly crucial to the functionality of the tear
      film. Surface pressure versus area isotherms, interfacial shear and extensional
      rheology, and Brewster angle microscopy (BAM) were used to characterize the
      Meibomian lipids from different species known to have different lipid
      compositions. The isotherms of humans, bovinae, wallabies, rabbits and kultarrs
      (a small desert marsupial) were qualitatively similar with little hysteresis
      between compression and expansion cycles. In contrast, several isocycles were
      necessary to achieve equilibrium behavior in the koala lipids. With the exception
      of kultarr lipids, the interfacial complex viscosity of all samples increased by
      one or two orders of magnitude between surface pressures of 5 mN/m and 20 mN/m
      and exhibited classic gel behavior at higher surface pressures. In contrast, the
      kultarr lipids were very fluid up to 22 mN/m; the behavior did not depend on
      surface pressure. Human lipids were very deformable in extensional flow and the
      BAM images revealed that the film became more homogeneous with compression as the
      elasticity of the film increased. The morphology of the kultarr lipids did not
      change with compression indicating a strong correlation between film structure
      and behavior. These results suggest that the lipid layer of the tear film forms a
      gel in vivo, which may aid in mechanically stabilization of the tear film.

PMID- 20156439
TI  - Protection of hippocampal neurogenesis by TAT-Bcl-x(L) after cerebral ischemia in
      mice.
AB  - Endogenous neurogenesis persists in the subgranular zone (SGZ) of the adult
      rodent brain. Cerebral ischemia stimulates endogenous neurogenesis involving
      proliferation, migration and differentiation of SGZ-derived neural precursor
      cells (NPC). However, the biological meaning of this phenomenon is limited by
      poor survival of NPC. In order to study the effects of an acute neuroprotective
      treatment on hippocampal endogenous neurogenesis after transient cerebral
      ischemia in mice, we applied a fusion protein consisting of the TAT domain of the
      HI virus with the anti-apoptotic Bcl-x(L). Intravenous injection of TAT-Bcl-x(L)
      resulted in reduced hippocampal cell injury for up to 4weeks after stroke as
      assessed by TUNEL and NeuN staining. This was in line with a TAT-Bcl-x(L)
      mediated reduced postischemic microglia activation. Analysis of endogenous
      hippocampal cell proliferation revealed an increased number of BrdU(+) cells in
      the TAT-Bcl-x(L) group 4weeks after stroke compared to animals treated with
      saline and TAT-HA (negative control). Cell proliferation in non-ischemic sham
      operated animals was not affected by TAT-Bcl-x(L). Twenty-eight days after stroke
      co-expression of BrdU(+) cells with the immature neuronal marker doublecortin was
      significantly increased in TAT-Bcl-x(L) animals. Although TAT-Bcl-x(L) treatment
      also resulted in an increased number of BrdU(+) cells expressing the mature
      neuronal marker NeuN, the total amount of these cells was low. These data show
      that TAT-Bcl-x(L) treatment yields both postischemic sustained hippocampal
      neuroprotection and increased survival of NPC rather than an induction of
      endogenous neurogenesis itself.

PMID- 20156440
TI  - Neural and environmental factors impacting maternal behavior differences in high-
      versus low-novelty-seeking rats.
AB  - Selective breeding of rats exhibiting differences in novelty-induced locomotion
      revealed that this trait predicts several differences in emotional behavior. Bred
      High Responders (bHRs) show exaggerated novelty-induced locomotion, aggression,
      and psychostimulant self-administration, compared to bred Low Responders (bLRs),
      which are inhibited and prone to anxiety- and depression-like behavior. Our
      breeding studies highlight the heritability of the bHR/bLR phenotypes, although
      environmental factors like maternal care also shape some aspects of these traits.
      We previously reported that HR vs. LR mothers act differently, but it was unclear
      whether their behaviors were genetically driven or influenced by their pups. The
      present study (a) used cross-fostering to evaluate whether the bHR/bLR maternal
      styles are inherent to mothers and/or are modulated by pups; and (b) assessed
      oxytocin and oxytocin receptor mRNA expression to examine possible underpinnings
      of bHR/bLR maternal differences. While bHR dams exhibited less maternal behavior
      than bLRs during the dark/active phase, they were very attentive to pups during
      the light phase, spending greater time passive nursing and in contact with pups
      compared to bLRs. Cross-fostering only subtly changed bHR and bLR dams' behavior,
      suggesting that their distinct maternal styles are largely inherent to the
      mothers. We also found elevated oxytocin mRNA levels in the supraoptic nucleus of
      the hypothalamus in bHR versus bLR dams, which may play some role in driving
      their behavior differences. Overall these studies shed light on the interplay
      between the genetics of mothers and infants in driving differences in maternal
      style.

PMID- 20156441
TI  - Attenuation of obesity by early-life food restriction in genetically hyperphagic
      male OLETF rats: peripheral mechanisms.
AB  - The alarming increase in childhood, adolescent and adult obesity has exposed the
      need for understanding early factors affecting obesity and for treatments that
      may help prevent or moderate its development. In the present study, we used the
      OLETF rat model of early-onset hyperphagia induced obesity, which become obese as
      a result of the absence of CCK(1) receptors, to examine the influence of partial
      food restriction on peripheral adiposity-related parameters during and after
      chronic and early short-term food restriction. Pair feeding (to the amount of
      food eaten by control, LETO rats) took place from weaning until postnatal day
      (PND) 45 (early) or from weaning until PND90 (chronic). We examined fat pad
      weight (brown, retroperitoneal, inguinal and epididymal); inguinal adipocyte size
      and number; and plasma leptin, oxytocin and creatinine levels. We also examined
      body weight, feeding efficiency and spontaneous intake after release from food
      restriction. The results showed that chronic food restriction produced
      significant reductions in adiposity parameters, hormones and body weight, while
      early food restriction successfully reduced long-term body weight, intake and
      adiposity, without affecting plasma measurements. Early (and chronic) dieting
      produced promising long-term effects that may imply the reorganization of both
      peripheral and central mechanisms that determine energy balance and further
      support the theory suggesting that early interventions may effectively moderate
      obesity, even in the presence of a genetic tendency.

PMID- 20156442
TI  - Behavioral implications of rapid changes in steroid production action in the
      brain [Commentary on Pradhan D.S., Newman A.E.M., Wacker D.W., Wingfield J.C.,
      Schlinger B.A. and Soma K.K.: Aggressive interactions rapidly increase androgen
      synthesis in the brain during the non-breeding season. Hormones and Behavior,
      2010].

PMID- 20156443
TI  - Surface antigen profiling of colorectal cancer using antibody microarrays with
      fluorescence multiplexing.
AB  - A procedure is described for the disaggregation of colorectal cancers (CRC) and
      normal intestinal mucosal tissues to produce suspensions of viable single cells,
      which are then captured on customized antibody microarrays recognising 122
      different surface antigens (DotScan CRC microarray). Cell binding patterns
      recorded by optical scanning of microarrays provide a surface profile of antigens
      on the cells. Sub-populations of cells bound on the microarray can be profiled by
      fluorescence multiplexing using monoclonal antibodies tagged with Quantum Dots or
      other fluorescent dyes. Surface profiles are presented for 6 CRC cell lines (T84,
      LIM1215, SW480, HT29, CaCo and SW620) and surgical samples from 40 CRC patients.
      Statistical analysis revealed significant differences between profiles for CRC
      samples and mucosal controls. Hierarchical clustering of CRC data identified
      several disease clusters that showed some correlation with clinico-pathological
      stage as determined by conventional histopathological analysis. Fluorescence
      multiplexing using Phycoerythrin- or Alexa Fluor 647-conjugated antibodies was
      more effective than multiplexing with antibodies labelled with Quantum Dots. This
      relatively simple method yields a large amount of information for each patient
      sample and, with further application, should provide disease signatures and
      enable the identification of patients with good or poor prognosis.

PMID- 20156444
TI  - Dimethyl sulfoxide (DMSO) exposure to human peripheral blood mononuclear cells
      (PBMCs) abolish T cell responses only in high concentrations and following
      coincubation for more than two hours.
AB  - Immunotherapies based on reinfusion of autologous cells incubated ex vivo with
      peptides reconstituted in toxic solvents, such as DMSO, are now performed on a
      routine basis. However, the toxic effects of the most common solvent used, DMSO,
      on T cell responses from human PBMCs, have not previously been evaluated in
      detail. Here, in preparation for a first-in-man human phase I vaccine trial
      comprising reinfusion of autologous HIV peptide-pulsed PBMCs, human PBMCs from
      healthy and HIV-infected donors were exposed in vitro to a range of DMSO
      concentrations, and for a range of time periods. Polychromatic flow cytometry was
      used to evaluate the influence of DMSO on functional T cell responses. We report
      that high concentrations of up to 10% of DMSO for 1 hour do not affect the cell
      viability, the magnitude or the functional profile of CD4(+) and CD8(+) T cell
      responses, regardless of antigen specificity and HLA class I restriction. In
      contrast, >2% for >2 hours compromises these responses. These data are relevant
      in the design of immunotherapies based on pulsing a large number of peptides onto
      antigen presenting cells prior to reinfusion.

PMID- 20156446
TI  - Vesicle permeabilization by purified soluble oligomers of prion protein: a
      comparative study of the interaction of oligomers and monomers with lipid
      membranes.
AB  - The conversion of normal cellular prion protein (PrP) into its pathological
      isoform, scrapie PrP, may occur at the cell surface or, more probably, in late
      endosomes. The early events leading to the structural conversion of PrP appear to
      be related to the presence of more or less stable soluble oligomers, which might
      mediate neurotoxicity. In the current study, we investigate the interaction of
      alpha-rich PrP monomers and beta-rich size-exclusion-chromatography-purified PrP
      oligomers with lipid membranes. We compare their structural properties when
      associated with lipid bilayers and study their propensities to permeabilize the
      membrane at physiological pH. We also study the influence of the N-terminal
      flexible region (residues 24-103) by comparing full-length PrP(24-234) and N
      terminally truncated PrP(104-234) oligomers. We showed that both 12-subunit
      oligomers cause an immediate and large increase in the permeability of the
      membrane, whereas equivalent amounts of monomeric forms cause no detectable
      leakage. Although the two monomeric PrP constructs undergo an alpha-to-beta
      conformational change when bound to the negatively charged membrane, only the
      full-length form of monomeric PrP has a weak fusogenic effect. Finally, the
      oligomers affect the integrity of the membrane differently from the monomers,
      independently of the presence of the N-terminal flexible domain. As for other
      forms of amyloidogenesis, a reasonable mechanism for the toxicity arising from
      PrP fibrillization must be associated with low-molecular-weight oligomeric
      intermediates, rather than with mature fibrils. Knowledge of the mechanism of
      action of these soluble oligomers would have a high impact on the development of
      novel therapeutic targets.

PMID- 20156445
TI  - Structure of avian thymic hormone, a high-affinity avian beta-parvalbumin, in the
      Ca2+-free and Ca2+-bound states.
AB  - Originally isolated on the basis of its capacity to stimulate T-cell maturation
      and proliferation, avian thymic hormone (ATH) is nevertheless a parvalbumin, one
      of two beta-lineage isoforms expressed in birds. We recently learned that
      addition of Ca(2+)-free ATH to a solution of 8-anilinonaphthalene-1-sulfonate
      (ANS) markedly increases ANS emission. This behavior, not observed in the
      presence of Ca(2+), suggests that apolar surface area buried in the Ca(2+)-bound
      state becomes solvent accessible upon Ca(2+) removal. In order to elucidate the
      conformational alterations that accompany Ca(2+) binding, we have obtained the
      solution structure of the Ca(2+)-free protein using NMR spectroscopy and compared
      it to the Ca(2+)-loaded protein, solved by X-ray crystallography. Although the
      metal-ion-binding (CD-EF) domains are largely coincident in the superimposed
      structures, a major difference is observed in the AB domains. The tight
      association of helix B with the E and F helices in the Ca(2+)-bound state is lost
      upon removal of Ca(2+), producing a deep hydrophobic cavity. The B helix also
      undergoes substantial rotation, exposing the side chains of F24, Y26, F29, and
      F30 to solvent. Presumably, the increase in ANS emission observed in the presence
      of unliganded ATH reflects the interaction of these hydrophobic residues with the
      fluorescent probe. The increased solvent exposure of apolar surface area in the
      Ca(2+)-free protein is consistent with previously collected scanning calorimetry
      data, which indicated an unusually low change in heat capacity upon thermal
      denaturation. The Ca(2+)-free structure also provides added insight into the
      magnitude of ligation-linked conformational alteration compatible with a high
      affinity metal-ion-binding signature. The exposure of substantial apolar surface
      area suggests the intriguing possibility that ATH could function as a reverse
      Ca(2+) sensor.

PMID- 20156447
TI  - Crystal structure of the electron carrier domain of the reaction center
      cytochrome c(z) subunit from green photosynthetic bacterium Chlorobium tepidum.
AB  - In green sulfur photosynthetic bacteria, the cytochrome c(z) (cyt c(z)) subunit
      in the reaction center complex mediates electron transfer mainly from
      menaquinol/cytochrome c oxidoreductase to the special pair (P840) of the reaction
      center. The cyt c(z) subunit consists of an N-terminal transmembrane domain and a
      C-terminal soluble domain that binds a single heme group. The periplasmic soluble
      domain has been proposed to be highly mobile and to fluctuate between
      oxidoreductase and P840 during photosynthetic electron transfer. We have
      determined the crystal structure of the oxidized form of the C-terminal
      functional domain of the cyt c(z) subunit (C-cyt c(z)) from thermophilic green
      sulfur bacterium Chlorobium tepidum at 1.3-A resolution. The overall fold of C
      cyt c(z) consists of four alpha-helices and is similar to that of class I
      cytochrome c proteins despite the low similarity in their amino acid sequences.
      The N-terminal structure of C-cyt c(z) supports the swinging mechanism previously
      proposed in relation with electron transfer, and the surface properties provide
      useful information on possible interaction sites with its electron transfer
      partners. Several characteristic features are observed for the heme environment:
      These include orientation of the axial ligands with respect to the heme plane,
      surface-exposed area of the heme, positions of water molecules, and hydrogen-bond
      network involving heme propionate groups. These structural features are essential
      for elucidating the mechanism for regulating the redox state of cyt c(z).

PMID- 20156448
TI  - Interactions of the Escherichia coli primosomal PriB protein with the single
      stranded DNA. Stoichiometries, intrinsic affinities, cooperativities, and base
      specificities.
AB  - Quantitative analysis of the interactions of the Escherichia coli primosomal PriB
      protein with a single-stranded DNA was done using quantitative fluorescence
      titration, photocrosslinking, and analytical ultracentrifugation techniques.
      Stoichiometry studies were done with a series of etheno-derivatives of single
      stranded (ss) DNA oligomers. Interactions with the unmodified nucleic acids were
      studied, using the macromolecular competition titration (MCT) method. The total
      site-size of the PriB dimer-ssDNA complex, i.e. the maximum number of nucleotides
      occluded by the PriB dimer in the complex, is 12+/-1 nt. The protein has a single
      DNA-binding site, which is located centrally within the dimer and has a
      functionally homogeneous structure. The stoichiometry and photocrosslinking data
      show that only a single monomer of the PriB dimer engages in interactions with
      the nucleic acid. The analysis of the PriB binding to long oligomers was done
      using a statistical thermodynamic model that takes into account the overlap of
      potential binding sites and cooperative interactions. The PriB dimer binds the
      ssDNA with strong positive cooperativity. Both the intrinsic affinity and
      cooperative interactions are accompanied by a net ion release, with anions
      participating in the ion exchange process. The intrinsic binding process is an
      entropy-driven reaction, suggesting strongly that the DNA association induces a
      large conformational change in the protein. The PriB protein shows a dramatically
      strong preference for the homo-pyrimidine oligomers with an intrinsic affinity
      higher by about three orders of magnitude, as compared to the homo-purine
      oligomers. The significance of these results for PriB protein activity is
      discussed.

PMID- 20156449
TI  - Polymeric structures and dynamic properties of the bacterial actin AlfA.
AB  - AlfA is a recently discovered DNA segregation protein from Bacillus subtilis that
      is distantly related to actin and the bacterial actin homologues ParM and MreB.
      Here we show that AlfA mostly forms helical 7/3 filaments, with a repeat of about
      180 A, that are arranged in three-dimensional bundles. Other polymorphic
      structures in the form of two-dimensional rafts or paracrystalline nets were also
      observed. Here AlfA adopted a 16/7 helical symmetry, with a repeat of about 387
      A. Thin polymers consisting of several intertwining filaments also formed.
      Observed helical symmetries of AlfA filaments differed from those of other
      members of the actin family: F-actin, ParM, or MreB. Both ATP and guanosine 5'
      triphosphate are able to promote rapid AlfA filament formation with almost equal
      efficiencies. The helical structure is only preserved under physiological salt
      concentrations and at a pH between 6.4 and 7.4, the physiological range of the
      cytoplasm of B. subtilis. Polymerization kinetics are extremely rapid and
      compatible with a cooperative assembly mechanism requiring only two steps:
      monomer activation followed by elongation, making AlfA one of the most efficient
      polymerizing motors within the actin family. Phosphate release lags behind
      polymerization, and time-lapse total internal reflection fluorescence images of
      AlfA bundles are consistent with treadmilling rather than dynamic microtubule
      like instability. High-pressure small angle X-ray scattering experiments reveal
      that the stability of AlfA filaments is intermediate between the stability of
      ParM and the stability of F-actin. These results emphasize that actin-like
      polymerizing machineries have diverged to produce a variety of filament
      geometries with diverse properties that are tailored for specific biological
      processes.

PMID- 20156450
TI  - Regulation of aerobic-to-anaerobic transitions by the FNR cycle in Escherichia
      coli.
AB  - The FNR (fumarate nitrate reduction) protein plays a central role in the global
      oxygen response of a variety of bacteria. In Escherichia coli, FNR is the master
      transcriptional regulator of the transition between aerobic and anaerobic growth.
      Regulation of FNR is achieved by cycling the molecule between three states in a
      process dependent on oxygen. In an effort to better understand the nature of this
      post-transcriptional cyclic regulatory mechanism, we formulated a kinetic model
      of the FNR protein and its regulation in E. coli. The values for the parameters
      of the model were fit to experimental data for the wild-type organism, and the
      model was validated by successfully predicting the behavior of fnr mutant strains
      characterized in the literature. We characterized the steady-state behavior of
      the FNR system by determining its sensitivity to changes in parameter values and
      its response to changes in the concentration of iron-sulfur cluster assembly
      proteins and the protease ClpXP. We also determined the steady-state induction
      characteristic that provides a direct estimate for the levels of the active form
      of FNR as a function of oxygen concentration. This result, in combination with
      reporter assays for expression of FNR target operons, gives an estimate for the
      equilibrium dissociation constant for the binding of active FNR to its
      recognition sequences in the DNA. Finally, we predicted the dynamics of the
      aerobic-to-anaerobic transition and determined distinct contributions to the
      dynamic profile of regulatory mechanisms operating at the transcriptional and
      post-translational levels.

PMID- 20156451
TI  - Exit strategies for charged tRNA from GluRS.
AB  - For several class I aminoacyl-tRNA synthetases (aaRSs), the rate-determining step
      in aminoacylation is the dissociation of charged tRNA from the enzyme. In this
      study, the following factors affecting the release of the charged tRNA from aaRSs
      are computationally explored: the protonation states of amino acids and
      substrates present in the active site, and the presence and the absence of AMP
      and elongation factor Tu. Through molecular modeling, internal pK(a)
      calculations, and molecular dynamics simulations, distinct, mechanistically
      relevant post-transfer states with charged tRNA bound to glutamyl-tRNA synthetase
      from Thermus thermophilus (Glu-tRNA(Glu)) are considered. The behavior of these
      nonequilibrium states is characterized as a function of time using dynamical
      network analysis, local energetics, and changes in free energies to estimate
      transitions that occur during the release of the tRNA. The hundreds of
      nanoseconds of simulation time reveal system characteristics that are consistent
      with recent experimental studies. Energetic and network results support the
      previously proposed mechanism in which the transfer of amino acid to tRNA is
      accompanied by the protonation of AMP to H-AMP. Subsequent migration of proton to
      water reduces the stability of the complex and loosens the interface both in the
      presence and in the absence of AMP. The subsequent undocking of AMP or tRNA then
      proceeds along thermodynamically competitive pathways. Release of the tRNA
      acceptor stem is further accelerated by the deprotonation of the alpha-ammonium
      group on the charging amino acid. The proposed general base is Glu41, a residue
      binding the alpha-ammonium group that is conserved in both structure and sequence
      across nearly all class I aaRSs. This universal handle is predicted through pK(a)
      calculations to be part of a proton relay system for destabilizing the bound
      charging amino acid following aminoacylation. Addition of elongation factor Tu to
      the aaRS.tRNA complex stimulates the dissociation of the tRNA core and the tRNA
      acceptor stem.

PMID- 20156452
TI  - Structures of PHR domains from Mus musculus Phr1 (Mycbp2) explain the loss-of
      function mutation (Gly1092-->Glu) of the C. elegans ortholog RPM-1.
AB  - PHR [PAM (protein associated with Myc)-HIW (Highwire)-RPM-1 (regulator of
      presynaptic morphology 1)] proteins are conserved, large multi-domain E3
      ubiquitin ligases with modular architecture. PHR proteins presynaptically control
      synaptic growth and axon guidance and postsynaptically regulate endocytosis of
      glutamate receptors. Dysfunction of neuronal ubiquitin-mediated proteasomal
      degradation is implicated in various neurodegenerative diseases. PHR proteins are
      characterized by the presence of two PHR domains near the N-terminus, which are
      essential for proper localization and function. Structures of both the first and
      second PHR domains of Mus musculus (mouse) Phr1 (MYC binding protein 2, Mycbp2)
      have been determined, revealing a novel beta sandwich fold composed of 11
      antiparallel beta-strands. Conserved loops decorate the apical side of the first
      PHR domain (MmPHR1), yielding a distinct conserved surface feature. The surface
      of the second PHR domain (MmPHR2), in contrast, lacks significant conservation.
      Importantly, the structure of MmPHR1 provides insights into a loss-of-function
      mutation, Gly1092-->Glu, observed in the Caenorhabditis elegans ortholog RPM-1.

PMID- 20156453
TI  - Structure of bacteriophage T4 endonuclease II mutant E118A, a tetrameric GIY-YIG
      enzyme.
AB  - Coliphage T4 endonuclease II (EndoII), encoded by gene denA, is a small (16 kDa,
      136 aa) enzyme belonging to the GIY-YIG family of endonucleases, which lacks a C
      terminal domain corresponding to that providing most of the binding energy in the
      structurally characterized GIY-YIG endonucleases, I-TevI and UvrC. In vivo, it is
      involved in degradation of host DNA, permitting scavenging of host-derived
      nucleotides for phage DNA synthesis. EndoII primarily catalyzes single-stranded
      nicking of DNA; 5- to 10-fold less frequently double-stranded breaks are
      produced. The Glu118Ala mutant of EndoII was crystallized in space group P2(1)
      with four monomers in the asymmetric unit. The fold of the EndoII monomer is
      similar to that of the catalytic domains of UvrC and I-TevI. In contrast to these
      enzymes, EndoII forms a striking X-shaped tetrameric structure composed as a
      dimer of dimers, with a protruding hairpin domain not present in UvrC or I-TevI
      providing most of the dimerization and tetramerization interfaces. A bound
      phosphate ion in one of the four active sites of EndoII likely mimics the
      scissile phosphate in a true substrate complex. In silico docking experiments
      showed that a protruding loop containing a nuclease-associated modular domain 3
      element is likely to be involved in substrate binding, as well as residues
      forming a separate nucleic acid binding surface adjacent to the active site. The
      positioning of these sites within the EndoII primary dimer suggests that the
      substrate would bind to a primary EndoII dimer diagonally over the active sites,
      requiring significant distortion of the enzyme or the substrate DNA, or both, for
      simultaneous nicking of both DNA strands. The scarcity of potential nucleic acid
      binding residues between the active sites indicates that EndoII may bind its
      substrate inefficiently across the two sites in the dimer, offering a plausible
      explanation for the catalytic preponderance of single-strand nicks. Mutations
      analyzed in earlier functional studies are discussed in their structural context.

PMID- 20156454
TI  - Visualizing the molecular interactions of a nucleotide analog, GS-9148, with HIV
      1 reverse transcriptase-DNA complex.
AB  - GS-9148 ([5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl]
      phosphonic acid) is a dAMP (2'-deoxyadenosine monophosphate) analog that
      maintains its antiviral activity against drug-resistant HIV. Crystal structures
      for HIV-1 reverse transcriptase (RT) bound to double-stranded DNA, ternary
      complexes with either GS-9148-diphosphate or 2'-deoxyadenosine triphosphate
      (dATP), and a post-incorporation structure with GS-9148 translocated to the
      priming site were obtained to gain insight into the mechanism of RT inhibition.
      The binding of either GS-9148-diphosphate or dATP to the binary RT-DNA complex
      resulted in the fingers subdomain closing around the incoming substrate. This
      produced up to a 9 A shift in the tips of the fingers subdomain as it closed
      toward the palm and thumb subdomains. GS-9148-diphosphate shows a similar binding
      mode as dATP in the nucleotide-binding site. Residues whose mutations confer
      resistance to nucleotide/nucleoside RT inhibitors, such as M184, Y115, L74, and
      K65, show little to no shift in orientation whether GS-9148-diphosphate or dATP
      is bound. One difference observed in binding is the position of the central ring.
      The dihydrofuran ring of GS-9148-diphosphate interacts with the aromatic side
      chain of Y115 more than does the ribose ring of dATP, possibly picking up a
      favorable pi-pi interaction. The ability of GS-9148-diphosphate to mimic the
      active-site contacts of dATP may explain its effective inhibition of RT and
      maintained activity against resistance mutations. Interestingly, the 2'-fluoro
      moiety of GS-9148-diphosphate was found in close proximity to the Q151 side
      chain, potentially explaining the observed moderately reduced susceptibly to GS
      9148 conferred by Q151M mutation.

PMID- 20156455
TI  - The asymmetric flagellar distribution and motility of Escherichia coli.
AB  - Rod-shaped bacteria such as Escherichia coli divide by binary fission. They
      inherit an old pole from the parent cell. The new pole is recently derived from
      the septum. Because the chemoreceptor accumulates linearly with time on the cell
      pole, the old pole carries more receptors than does the new pole. Here, further
      evidence is provided that the old pole appears more frequently at the rear when
      bacteria swim. This phenomenon had been observed, yet not extensively explored in
      the literature. The biased swimming orientation is the consequence of the
      asymmetric distribution of flagella over the cell surface. On about 75% of cells,
      there are more flagella on the old-pole half of the cell than on the new-pole
      half, regardless of growth conditions. Most flagella are lateral, and few were
      found on the cell pole per se. The asymmetric flagellar distribution makes cells
      more efficient in chemotaxis. Both swimming orientation and receptor localization
      are components of chemotaxis, by which bacteria follow environmental stimuli. If
      unipolarly flagellated cells, such as the swarmer cells of Caulobacter
      crescentus, are regarded as 100% polar with respect to chemotaxis, E. coli is
      about 75%. The difference is quantitative. The peritrichous flagellation might
      enhance the motility and chemotaxis in the viscous environment of enteric
      bacteria.

PMID- 20156456
TI  - HBx-induced hepatic steatosis and apoptosis are regulated by TNFR1- and NF-kappaB
      dependent pathways.
AB  - Hepatitis B virus X (HBx) protein is an important regulator of hepatic steatosis
      observed in patients with hepatitis B virus; however, its underlying molecular
      mechanism remains unclear. TNF receptor 1 (TNFR1) is an essential pathway for the
      HBx-mediated nuclear factor kappaB (NF-kappaB) activation involved in hepatic
      liver injury. Here, we show that HBx-mediated steatosis and apoptosis are
      regulated by TNFR1- and NF-kappaB-dependent pathways. HBx-mediated tumor necrosis
      factor alpha (TNF-alpha) production and NF-kappaB activation were completely
      diminished in anti-TNF-alpha-treated cells and TNF-alpha(-)(/-) or TNFR1(-/-)
      mice. HBx and TNFR1, which are potentiated by TNF-alpha, are physically
      associated and colocalize in the plasma membrane. Similarly, TNFR1 depletion
      inhibits lipid droplets, and lipogenic genes such as sterol regulatory element
      binding protein (SREBP) 1 and peroxisome proliferator-activated receptor (PPAR)
      gamma increased in HBx-Tg mice and HepG2-GFPHBx stable cells. Furthermore, lipid
      accumulation and expression of SREBP1c and PPAR gamma are significantly increased
      in AdHBx-GFP-injected (intravenous) wild-type mice, but not in TNFR1(-/-) mice.
      HBx-enhanced transcriptional activities of SREBP1 and PPAR gamma are
      significantly attenuated by the NF-kappaB inhibitor Bay 11-7082, as well as by
      TNFR1 depletion. Also, AdHBx-GFP potentiates TNF-alpha-induced apoptosis, which
      is completely inhibited in TNFR1-depleted cells. Our results suggest that HBx
      induced NF-kappaB activation was mediated by direct interaction with TNFR1 and
      thereby induced TNF-alpha production. HBx-induced NF-kappaB activation is also
      associated with the induction of hepatic steatosis and apoptosis, which is
      determined by a TNFR1-dependent pathway.

PMID- 20156457
TI  - The subunit interfaces of weakly associated homodimeric proteins.
AB  - We analyzed subunit interfaces in 315 homodimers with an X-ray structure in the
      Protein Data Bank, validated by checking the literature for data that indicate
      that the proteins are dimeric in solution and that, in the case of the "weak"
      dimers, the homodimer is in equilibrium with the monomer. The interfaces of the
      42 weak dimers, which are smaller by a factor of 2.4 on average than in the
      remainder of the set, are comparable in size with antibody-antigen or protease
      inhibitor interfaces. Nevertheless, they are more hydrophobic than in the average
      transient protein-protein complex and similar in amino acid composition to the
      other homodimer interfaces. The mean numbers of interface hydrogen bonds and
      hydration water molecules per unit area are also similar in homodimers and
      transient complexes. Parameters related to the atomic packing suggest that many
      of the weak dimer interfaces are loosely packed, and we suggest that this
      contributes to their low stability. To evaluate the evolutionary selection
      pressure on interface residues, we calculated the Shannon entropy of homologous
      amino acid sequences at 60% sequence identity. In 93% of the homodimers, the
      interface residues are better conserved than the residues on the protein surface.
      The weak dimers display the same high degree of interface conservation as other
      homodimers, but their homologs may be heterodimers as well as homodimers. Their
      interfaces may be good models in terms of their size, composition, and
      evolutionary conservation for the labile subunit contacts that allow protein
      assemblies to share and exchange components, allosteric proteins to undergo
      quaternary structure transitions, and molecular machines to operate in the cell.

PMID- 20156458
TI  - Non-additivity of functional group contributions in protein-ligand binding: a
      comprehensive study by crystallography and isothermal titration calorimetry.
AB  - Additivity of functional group contributions to protein-ligand binding is a very
      popular concept in medicinal chemistry as the basis of rational design and
      optimized lead structures. Most of the currently applied scoring functions for
      docking build on such additivity models. Even though the limitation of this
      concept is well known, case studies examining in detail why additivity fails at
      the molecular level are still very scarce. The present study shows, by use of
      crystal structure analysis and isothermal titration calorimetry for a congeneric
      series of thrombin inhibitors, that extensive cooperative effects between
      hydrophobic contacts and hydrogen bond formation are intimately coupled via
      dynamic properties of the formed complexes. The formation of optimal lipophilic
      contacts with the surface of the thrombin S3 pocket and the full desolvation of
      this pocket can conflict with the formation of an optimal hydrogen bond between
      ligand and protein. The mutual contributions of the competing interactions depend
      on the size of the ligand hydrophobic substituent and influence the residual
      mobility of ligand portions at the binding site. Analysis of the individual
      crystal structures and factorizing the free energy into enthalpy and entropy
      demonstrates that binding affinity of the ligands results from a mixture of
      enthalpic contributions from hydrogen bonding and hydrophobic contacts, and
      entropic considerations involving an increasing loss of residual mobility of the
      bound ligands. This complex picture of mutually competing and partially
      compensating enthalpic and entropic effects determines the non-additivity of free
      energy contributions to ligand binding at the molecular level.

PMID- 20156459
TI  - Glucagon fibril polymorphism reflects differences in protofilament backbone
      structure.
AB  - Amyloid fibrils formed by the 29-residue peptide hormone glucagon at different
      concentrations have strikingly different morphologies when observed by
      transmission electron microscopy. Fibrils formed at low concentration (0.25
      mg/mL) consist of two or more protofilaments with a regular twist, while fibrils
      at high concentration (8 mg/mL) consist of two straight protofilaments. Here, we
      explore the structural differences underlying glucagon polymorphism using
      proteolytic degradation, linear and circular dichroism, Fourier transform
      infrared spectroscopy (FTIR), and X-ray fiber diffraction. Morphological
      differences are perpetuated at all structural levels, indicating that the two
      fibril classes differ in terms of protofilament backbone regions, secondary
      structure, chromophore alignment along the fibril axis, and fibril
      superstructure. Straight fibrils show a conventional beta-sheet-rich far-UV
      circular dichroism spectrum whereas that of twisted fibrils is dominated by
      contributions from beta-turns. Fourier transform infrared spectroscopy confirms
      this and also indicates a more dense backbone with weaker hydrogen bonding for
      the twisted morphology. According to linear dichroism, the secondary structural
      elements and the aromatic side chains in the straight fibrils are more highly
      ordered with respect to the alignment axis than the twisted fibrils. A series of
      highly periodical reflections in the diffractogram of the straight fibrils can be
      fitted to the diffraction pattern expected from a cylinder. Thus, the highly
      integrated structural organization in the straight fibril leads to a compact and
      highly uniform fibril with a well-defined edge. Prolonged proteolytic digestion
      confirmed that the straight fibrils are very compact and stable, while parts of
      the twisted fibril backbone are much more readily degraded. Differences in the
      digest patterns of the two morphologies correlate with predictions from two
      algorithms, suggesting that the polymorphism is inherent in the glucagon
      sequence. Glucagon provides a striking illustration of how the same short
      sequence can be folded into two remarkably different fibrillar structures.

PMID- 20156460
TI  - Analysis of retinal circulation using an image-based network model of retinal
      vasculature.
AB  - This paper presents the results of a circulation analysis using an image based
      network model of a murine retinal vasculature, which closely represents the 3D
      vascular distribution of the retina. The uneven distribution of the red blood
      cells at vascular network bifurcations (i.e., plasma skimming effect), the
      microvascular diameter effect (i.e., Fahraeus-Lindqvist effect) and the role of
      endothelium surface layer (i.e., in vivo viscosity) were considered in
      determining the viscosity of the blood in the retinal vessel segments. The study
      yielded detailed distributions of the hemodynamic quantities in the arterial and
      venous trees shown in various anatomical based contour plots. Quantitative
      analysis was also carried out based on statistical distributions. The analysis
      shows that the distribution of the blood hematocrit (H(D)) in the retinal network
      is very non-uniform, with lower values at the pre-equator region (near the optic
      disc) and higher values in the equator region of the retina. This has significant
      influence on the distribution of apparent viscosity, pressure and wall shear
      stress (WSS) in the vasculature. The viscosity is generally higher in smaller
      vessels (i.e., pre-capillary vessels) but exceptions occur in some vessels where
      the H(D) is small. WSS is greater in smaller vessels located near the optic disc
      than that in the mainstream retinal vessels. The results presented can be
      directly useful to ophthalmologists and researchers working with retinal
      vasculature.

PMID- 20156461
TI  - Wavelet analysis of cerebral oxygenation signal measured by near infrared
      spectroscopy in subjects with cerebral infarction.
AB  - The objective of this study is to assess the cerebral oxygenation oscillations in
      subjects with cerebral infarction (CI) based on the wavelet transform of near
      infrared spectroscopy (NIRS) signals. A total of twenty subjects were recruited
      from a local hospital to participate in this study. The subjects lay in the
      supine position and cerebral oxygenation signal was monitored for 20 min from the
      frontal lobe using NIRS. With spectral analysis based on wavelet transform, five
      frequency intervals were identified (I, 0.005-0.02 Hz, II, 0.02-0.06 Hz, III,
      0.06-0.15 Hz, IV, 0.15-0.40 Hz and V, 0.40-2.0 Hz). The amplitude of the [HbO(2)]
      in frequency interval I (0.005-0.02 Hz), II (0.02-0.06 Hz), III (0.06-0.15 Hz)
      and V(0.15-2 Hz) for the subjects with CI were found to be significantly lower by
      36%, 45%, 50% and 69% compared to that for the normal subjects (p<0.05). The
      amplitude of the [Hb] in frequency interval I (0.005-0.02 Hz), II (0.02-0.06 Hz)
      and V(0.15-2 Hz) for the subjects with CI were found to be significantly lower by
      40%, 36% and 69% compared to that for the normal subjects (p<0.05). The reduction
      of spontaneous oscillations in subjects with CI may suggest an increased
      stiffness in arterial vessels. This indicates the possibility of applying
      spontaneous oscillations to assessing atherosclerosis in high risk subjects for
      CI based on the wavelet transform of NIRS signals.

PMID- 20156462
TI  - Neurochemical basis for symptomatic treatment of Alzheimer's disease.
AB  - Neuron and synapse loss together with neurotransmitter dysfunction have, along
      with Abeta deposition and neurofibrillary tangles, been recognized as hallmarks
      of Alzheimer's disease (AD). Furthermore, clinical and preclinical studies point
      to neuronal loss and associated neurochemical alterations of several transmitter
      systems as a main factor underlying both cognitive and neuropsychiatric symptoms.
      Treatment for the cognitive decline in AD, based on early findings of a
      cholinergic deficit, has been in the clinic for more than a decade but provides
      only modest benefit in most patients. Therefore there is still considerable scope
      for new treatments that demonstrate greater efficacy against cognitive
      dysfunction in spite of the fact that the mainstays of current treatments, the
      cholinesterase inhibitors Aricept, Exelon and Reminyl (Razadyne) will become
      generic over the next few years. However, the most important area for drug
      development is for the treatment of behavioural disturbance in AD since many
      existing treatments have limited efficacy and have potentially life-threatening
      side effects. This review examines the neurochemical underpinning of both
      cognitive and neuropsychiatric symptoms in dementia and provides some basis for
      rational drug development.

PMID- 20156463
TI  - Oxytocin induces penile erection when injected into the ventral subiculum: role
      of nitric oxide and glutamic acid.
AB  - Oxytocin (100 ng) induces penile erection when injected unilaterally into the
      ventral subiculum of the hippocampus of male rats. The pro-erectile effect
      started mostly 30 min after treatment and occurred 15 min after an increase in
      both nitric oxide (NO) production, measured by the concentration of NO(2)(-) and
      NO(3)(-), the main metabolites of newly formed NO, and extra-cellular glutamic
      acid concentration in the dialysate obtained from the ventral subiculum by
      intracerebral microdialysis. These responses were abolished by
      d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (2 microg), an oxytocin receptor
      antagonist, S-methyl-L-thiocitrulline (SMTC), a selective inhibitor of neuronal
      NO-synthase (25 microg), and haemoglobin, a NO scavenger (25 microg), given into
      the ventral subiculum before oxytocin. Unlike d(CH(2))(5)Tyr(Me)(2)-Orn(8)
      vasotocin, SMTC and haemoglobin, (+)MK-801 (5 microg), a noncompetitive
      antagonist of NMDA receptors abolished oxytocin-induced penile erection, but
      reduced only partially the increase in NO production and extra-cellular glutamic
      acid. As NMDA (0.25-1 microg) injected into the ventral subiculum induces penile
      erection episodes, which also occurred with an increase of NO production and
      extra-cellular glutamic acid, and NMDA responses were abolished by (+)MK-801 (5
      microg), but not by SMTC (25 microg) or haemoglobin (25 microg), injected into
      the ventral subiculum, these results show that oxytocin injected into the ventral
      subiculum increases NO production by activating its own receptors. NO in turn
      increases glutamic acid neurotransmission, leading to penile erection, possibly
      through neural (glutamatergic) efferent projections from the ventral subiculum to
      extra-hippocampal brain areas (e.g., prefrontal cortex) modulating the activity
      of mesolimbic dopaminergic neurons.

PMID- 20156464
TI  - Faux pas deficits in people with medial frontal lesions as related to impaired
      understanding of a speaker's mental state.
AB  - This study examined the nature of deficits in mentalizing, the ability to read
      the mental state of other people, as measured by a faux pas task in people with
      medial frontal lesions. A total of 56 Mandarin-speaking Chinese individuals
      participated (9 participants with medial frontal lesions, 12 participants with
      lateral frontal lesions, 5 participants with non-frontal lesions, and 30 healthy
      controls). The faux pas test ascertained the participants' ability to identify
      and understand a social faux pas, and to understand the mental states of the
      characters (the speaker and the recipient in a conversation with a social faux
      pas). Although the participants with medial frontal lesions performed less well
      than the other clinical participants and the control participants on all aspects
      of the faux pas test, the most significant deficit was observed in understanding
      mental states and hence inferring the speaker's intentions. The performance on
      the various aspects of decoding a social faux pas by people with medial frontal
      lesions suggests that the cognitive processes, and hence the respective neural
      correlates subserving these various processes, may be different. Our results add
      to existing literature and illustrate the very nature of deficits of mentalizing,
      measured by a faux pas test, experienced by people with medial frontal lesions.
      The data have also prompted that future behavioral and neuroimaging studies may
      be applied to further decode both the neural mechanisms and the cognitive
      variables affecting "mentalizing".

PMID- 20156465
TI  - Physiological variables explain mineral intake in Iberian red deer.
AB  - Foraging theory predicts that animals should be able to assess nutrient content
      of food sources and adjust their diet according to needs. As many minerals are
      essential nutrients, animals should be able to discriminate and consume the
      amount needed for each mineral. Although this has been proved for sodium and
      phosphorus, it is not clear if animals can discriminate among other essential
      minerals, and if they do so based on physiological needs. Requirements depend on
      sex, age, and physiological status, and thus usually vary greatly among
      individuals. Thus, if animals behave as optimal foragers of minerals, factors
      affecting individual physiological needs should also affect intake behaviour of
      each mineral. We tested this prediction in Iberian red deer. During two lactation
      periods a series of containers with different minerals, most of them diluted in
      salt, were offered to 59 adult hinds and their calves while consumption behaviour
      was recorded. Study animals were monitored weekly and milk production was
      assessed during the experiment. All the lactation variables influenced mineral
      consumption, and the effect differed for each mineral. Models explained a higher
      proportion of variability in calf than hind behaviour, reflecting probably a
      greater constraint as a result of growth needs. Thus, results show that deer can
      select mineral content in their diet and that selection is shaped by
      physiological effort as expected if consumption is driven by physiological needs.

PMID- 20156466
TI  - Green tea catechins, caffeine and body-weight regulation.
AB  - The global prevalence of obesity has increased considerably in the last decade.
      Tools for obesity management including caffeine, and green tea have been proposed
      as strategies for weight loss and weight maintenance. These ingredients may
      increase energy expenditure and have been proposed to counteract the decrease in
      metabolic rate that is present during weight loss. Positive effects on body
      weight management have been shown using green tea mixtures. Green tea, by
      containing both tea catechins and caffeine, may act through inhibition of
      catechol O-methyl-transferase, and inhibition of phosphodiesterase. Here the
      mechanisms may also operate synergistically. A green tea-caffeine mixture
      improves weight maintenance, through thermogenesis, fat oxidation, and sparing
      fat free mass. The sympathetic nervous system is involved in the regulation of
      lipolysis, and the sympathetic innervation of white adipose tissue may play an
      important role in the regulation of total body fat in general. Taken together,
      these functional ingredients have the potential to produce significant effects on
      metabolic targets such as thermogenesis, and fat oxidation. An ethnic or genetic
      effect, and habitual caffeine or green tea catechin intake may act as
      confounders; this remains to be revealed.

PMID- 20156467
TI  - Formalin-induced nociceptive behavior and c-Fos expression in middle-aged female
      rats.
AB  - The impact of the estrous cycle on the nociceptive response in middle-aged female
      rats was assessed using the formalin test and c-Fos immunoreactivity as a marker
      of neural activation. Young (2-month-old) and middle-aged (11-month-old) rats
      were examined, dividing the middle-aged rats into two groups based on their
      estrous cycle: regular 4-day estrous cycle and irregular estrous cycle. The right
      hind paw was subcutaneously injected with 50microl of 2% formalin or saline as a
      control. Behavioral changes were observed for 1h. Cycling rats were used during
      proestrus. Middle-aged female rats had a significantly higher score for
      nociceptive behavior compared to young rats, irrespective of estrous cyclicity,
      which suggests that aging, not the ability to maintain estrous cyclicity, causes
      hypersensitivity to the formalin injection. Immunohistochemical analysis found
      that the brain response to formalin injection was also more sensitive in middle
      aged rats than young rats; a significant increase in the number of c-Fos
      immunoreactive cells was found in the ventral portion of the lateral septum of
      middle-aged rats injected with formalin compared to young and middle-aged rats
      injected with saline, irrespective of estrous cyclicity. Based on these results,
      we conclude that the sensitivity to painful stimuli in middle-aged female rats,
      which are in a neuroendocrine state similar to pre- and peri-menopausal women, is
      associated with age and not affected by reproductive ability.

PMID- 20156468
TI  - Sex-dependent antidepressant effects of lower doses of progesterone in rats.
AB  - Major depression is more prevalent among women than men, and progesterone might
      be involved in the mechanisms that generate these differences. Progesterone is
      clinically used for women in several reproductive events, but its antidepressant
      effect is unclear. Animal studies showed the interference of progesterone on
      depressive behaviors of rodents, but they are inconclusive, and no study compared
      different treatment durations. This study investigated the antidepressant effect
      of low doses of progesterone in male and female rats under acute or chronic
      administration. Male and female Wistar rats in different phases of the estrous
      cycle were acutely administered different doses of progesterone (0.0, 0.4. 0.8
      and 1.2mg/kg) and tested in the forced swimming test (FST). The lowest dose of
      progesterone (0.4 mg/kg) was chronically administered during two complete estrous
      cycles and diestrous II female and male rats were tested in the FST. Progesterone
      decreased depressive-like behaviors only in chronically treated diestrous II
      female rats and increased immobility in male rats. This low dose of progesterone
      did not interfere in the hormonal cycling in female rats. Results also showed
      that diestrous II female rats had greater immobility than male rats in the FST.
      The greater immobility of diestrous II female rats shows that rats in this
      estrous phase present more depressive-like behaviors that may be associated with
      their lower serum levels of progesterone. We showed that progesterone chronically
      administered at low doses reverses these depressive-like behaviors and has an
      antidepressant effect during the diestrous II phase of the estrous cycle.

PMID- 20156470
TI  - Mg(II)-induced binding of factor IX-binding protein from the venom of Agkistrodon
      Halys Pallas with factor Xa.
AB  - Factor IX-binding protein (AHP IX-bp), a Ca2+- and Zn2+-binding protein from the
      venom of Agkistrodon Halys Pallas was reported to bind specifically with factor
      IX in a Zn2+-dependent manner. Here we have purified AHP IX-bp by a simple two
      step of chromatography procedure and found that AHP IX-bp also binds factor Xa
      (FXa) with high binding-affinity in a Mg2+-dependent manner. Although Mg2+ ions
      have a significantly low binding-affinity for apo-AHP IX-bp as determined by
      isothermal titration calorimetry, they can induce the binding of apo-AHP IX-bp
      with FXa even in the absence of Ca2+ as determined by native PAGE and surface
      plasmon resonance. Mg2+ ions are required to maintain in vivo function of FX Gla
      domain for its recognition of AHP IX-bp. Both Ca2+ and Zn2+ ions fail to induce
      the binding between apo-AHP IX-bp and FXa. The abundant Mg2+ ions in blood play
      an important role in the anticoagulation of AHP IX-bp.

PMID- 20156471
TI  - WITHDRAWN: A revised amino group pK(a) for prymnesins does not provide decisive
      evidence for a pH-dependent mechanism of Prymnesium parvum's toxicity.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi:10.1016/j.toxicon.2010.02.008. The
      duplicate article has therefore been withdrawn.

PMID- 20156469
TI  - Epigenetic regulation of the expression of genes involved in steroid hormone
      biosynthesis and action.
AB  - Steroid hormones participate in organ development, reproduction, body
      homeostasis, and stress responses. The steroid machinery is expressed in a
      development- and tissue-specific manner, with the expression of these factors
      being tightly regulated by an array of transcription factors (TFs). Epigenetics
      provides an additional layer of gene regulation through DNA methylation and
      histone tail modifications. Evidence of epigenetic regulation of key
      steroidogenic enzymes is increasing, though this does not seem to be a
      predominant regulatory pathway. Steroid hormones exert their action in target
      tissues through steroid nuclear receptors belonging to the NR3A and NR3C
      families. Nuclear receptor expression levels and post-translational modifications
      regulate their function and dictate their sensitivity to steroid ligands. Nuclear
      receptors and TFs are more likely to be epigenetically regulated than proteins
      involved in steroidogenesis and have secondary impact on the expression of these
      steroidogenic enzymes. Here we review evidence for epigenetic regulation of
      enzymes, transcription factors, and nuclear receptors related to steroid
      biogenesis and action.

PMID- 20156472
TI  - Simulated microgravity alters growth and microcystin production in Microcystis
      aeruginosa (cyanophyta).
AB  - Recent researches indicated that microgravity can increase pathogenic bacteria
      virulence. We presumed that microgravity might affect the toxin production of
      toxic cyanobacteria too. Microcystis aeruginosa PCC7806 was chosen as the model
      organism to investigate the effects of simulated microgravity (SMG) on the growth
      and toxin production of toxic cyanobacteria. SMG could inhibit the growth of M.
      aeruginosa, which resulted in decreased cell number and lower specific growth
      rate after 20-day treatment. M. aeruginosa sensed the reduced gravity very
      quickly and immediately up-regulated its microcystin (MC) synthesis and exudation
      in 2 days. Subsequently, the intracellular MC content fell back since the 8(th)
      day and was stable around the initial level in the following days, suggesting a
      quick adaptation to the reduced gravity. SMG had negative effects on the
      photochemical system and the absorption of phosphorus in most time. However, the
      photosynthetic pigment concentrations and nitrogen absorption used to be
      transitorily stimulated upwards by SMG. It was assumed that SMG inhibited cell
      growth by interfering its photosynthesis and phosphorus uptake, while the
      enhanced MC production was related with pigment and nitrogen metabolisms. This
      study reveals that SMG is a novel environmental signal which inhibits growth and
      enhances MC production of M. aeruginosa.

PMID- 20156474
TI  - Object speed derived from the integration of motion in the image plane and motion
      in-depth signaled by stereomotion and looming.
AB  - We investigate the influence of local motion in the retinal image plane on the
      perception of speed-in-depth. Observers judged the apparent speed-in-depth of a
      square plane of dynamic dots that moved towards the observer. Dots forming the
      surface of the plane underwent random-direction motion in the image plane. We
      examined the consequences of changing the dots' image-plane speed on the apparent
      speed of the stimulus as it traversed depth, where depth is signaled by
      stereomotion or looming. Results for both the stereomotion and looming conditions
      indicate that as the speed of random-direction motion in the image plane
      increases, the apparent speed-in-depth of the stimulus also increases. When
      stereomotion was used to signal motion-in-depth, the speed judgment is adequately
      modeled by the resultant of a vector sum of dot-speed in the image plane and
      speed-in-depth. However, when looming was used to define motion-in-depth, a
      different pattern of results was found - the apparent speed-in-depth is lower
      than the actual speed-in-depth, and the results are best predicted by simple
      averaging. Our results demonstrate that the integration of speed in the image
      plane and speed-in-depth, to determine object speed, is dependent on the type of
      cue used to signal motion-in-depth, and this difference is a consequence of the
      ways in which looming and stereomotion cue motion-in-depth. Looming is derived
      not at a local stage of motion analysis, but is available only via global
      integration of local velocities, and consequently global speed conforms to the
      average speed. Stereomotion, on the other hand, provides an effective cue for
      individuating local velocities in depth.

PMID- 20156473
TI  - Reading speed in the peripheral visual field of older adults: Does it benefit
      from perceptual learning?
AB  - Enhancing reading ability in peripheral vision is important for the
      rehabilitation of people with central-visual-field loss from age-related macular
      degeneration (AMD). Previous research has shown that perceptual learning, based
      on a trigram letter-recognition task, improved peripheral reading speed among
      normally-sighted young adults (Chung, Legge, & Cheung, 2004). Here we ask whether
      the same happens in older adults in an age range more typical of the onset of
      AMD. Eighteen normally-sighted subjects, aged 55-76years, were randomly assigned
      to training or control groups. Visual-span profiles (plots of letter-recognition
      accuracy as a function of horizontal letter position) and RSVP reading speeds
      were measured at 10 degrees above and below fixation during pre- and post-tests
      for all subjects. Training consisted of repeated measurements of visual-span
      profiles at 10 degrees below fixation, in four daily sessions. The control
      subjects did not receive any training. Perceptual learning enlarged the visual
      spans in both trained (lower) and untrained (upper) visual fields. Reading speed
      improved in the trained field by 60% when the trained print size was used. The
      training benefits for these older subjects were weaker than the training benefits
      for young adults found by Chung et al. Despite the weaker training benefits,
      perceptual learning remains a potential option for low-vision reading
      rehabilitation among older adults.

PMID- 20156475
TI  - Tri-stable stimuli reveal interactions among subsequent percepts: rivalry is
      biased by perceptual history.
AB  - In rivalry, constant stimuli allow several interpretations ("percepts"). Percepts
      are characterized by their probability to occur and by the duration of their
      dominance. During continuous presentation of bi-stable stimuli, both percept
      probabilities are trivially 50%. To disentangle the processes triggering a
      percept from those stabilizing it, we introduce tri-stable stimuli having three
      percepts. We find the probability and dominance duration of a percept
      independently adjustable. Percept probabilities and dominance durations show
      mutual dependencies across several perceptual switches. Consequently, the current
      perceptual experience depends on perceptual history; therefore, rivalry--even for
      continuous presentation--is not a memory-less process.

PMID- 20156476
TI  - Flunitrazepam in combination with alcohol engenders high levels of aggression in
      mice and rats.
AB  - RATIONALE: Higher doses of benzodiazepines and alcohol induce sedation and sleep;
      however, in low to moderate doses these drugs can increase aggressive behavior.
      OBJECTIVES: To assess firstly the effects of ethanol, secondly the effects of
      flunitrazepam, a so-called club drug, and thirdly the effects of flunitrazepam
      plus alcohol on aggression in mice and rats. METHODS: Exhaustive behavioral
      records of confrontations between a male resident and a male intruder were
      obtained twice a week, using CF-1 mice and Wistar rats. The salient aggressive
      and non-aggressive elements in the resident's repertoire were analyzed.
      Initially, the effects of ethanol (1.0g/kg), and secondly flunitrazepam (0; 0.01;
      0.1; and 0.3mg/kg) were determined in all mice and rats; subsequently,
      flunitrazepam or vehicle, given intraperitoneally (0; 0.01; 0.1; and 0.3mg/kg)
      was administered plus ethanol 1.0g/kg or vehicle via gavage. RESULTS: The most
      significant finding is the escalation of aggression after a moderate dose of
      ethanol, and a low dose of flunitrazepam. The largest increase in aggressive
      behavior occurred after combined flunitrazepam plus ethanol treatment in mice and
      rats. CONCLUSIONS: Ethanol can heighten aggressive behavior and flunitrazepam
      further increases this effect in male mice and rats.

PMID- 20156477
TI  - Induction of tumoricidal activity in mouse peritoneal macrophages by ginseng
      polysaccharide.
AB  - This study examined the effects of ginseng polysaccharide (GPS) on mouse
      peritoneal macrophage (PM)-mediated cytotoxicity towards K562, HL-60, or KG1alpha
      cells. GPS had no direct effect on killing of tumor cells. However, when mouse
      PMs were treated with GPS, cytotoxic activity against K562, HL-60, or KG1alpha
      cells was significantly induced. In addition, phagocytic activity was enhanced in
      GPS-treated mouse PMs compared to the control. The expressions of CD(68), ACP and
      alpha-ANE in mouse PMs were increased by the treatment with GPS. Moreover, the
      levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 (IL-1), IL-6 were increased and the production of nitric oxide (NO)
      was enhanced. Taken together, these results suggest that GPS possess a potent
      antitumor activity by stimulating macrophage and a potentiality as an
      immunomodulator against diseases such as cancer.

PMID- 20156478
TI  - Differential gene expression of gamma-actin, Toll-like receptor 2 (TLR-2) and
      interleukin-1 receptor-associated kinase 4 (IRAK-4) in Mya arenaria haemocytes
      induced by in vivo infections with two Vibrio splendidus strains.
AB  - Immune function gene expression in Mya arenaria haemocytes was evaluated
      following in vivo infection with Vibrio splendidus LGP32-GFP and 7SHRW.
      Elongation factor 1alpha (EF-1alpha) with 2 (EF-2), after challenge with LGP32
      GFP, and EF-1alpha with the ribosomal protein S-18, after challenge with 7SHRW,
      were found to be the most stable housekeeping genes. Using these internal
      controls and comparing the regulation induced by both strains, up-regulation of
      gamma-actin, down-regulation of TLR-2 and up-regulation of IRAK-4 was
      significantly higher after challenge with LGP32-GFP (p<0.001, p=0.001 and p<0.05,
      respectively). These results suggest specific responses at a molecular level
      modulated by the bacterial strains. LGP32-GFP induced marked responses which
      coincide with a similar trend previously found on phenotypic responses under our
      experimental model.

PMID- 20156479
TI  - Identification of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) isoforms
      in the Pekin duck.
AB  - Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152) is an inhibitory T
      cell receptor predominately expressed on activated T cells. The duck CTLA-4
      (DuCTLA-4) cDNA and a transcript lacking the predicted transmembrane encoding
      region (DuCTLA-4DeltaTM) were isolated from splenocytes using RT-PCR. The
      predicted DuCTLA-4 protein showed an identity of 92%, 49% and 47% with chicken,
      human and mouse homologues, respectively. Sequence comparison revealed
      conservation of residues implicated in the B7 ligand binding, disulfide linkages,
      glycosylation and intracellular signaling. DuCTLA-4 mRNA was predominately
      expressed in primary and secondary immune organs. DuCTLA-4 and DuCTLA-4DeltaTM
      transcripts were differentially regulated in PBMCs. Flow cytometric analysis
      showed constitutive expression of DuCTLA-4 protein on freshly isolated PBMCs and
      a modest increase upon mitogen stimulation. Our observations suggest that DuCTLA
      4 and its isoform DuCTLA-4DeltaTM evolved before the divergence of birds and
      mammals. Both DuCTLA-4 isoforms have significant structural homology to mammalian
      CTLA-4 proteins but their individual roles in the regulation of duck immune
      responses remains to be elucidated.

PMID- 20156480
TI  - The neurobiology of repetitive behavior: of mice....
AB  - Repetitive and stereotyped behavior is a prominent element of both animal and
      human behavior. Similar behavior is seen across species, in diverse
      neuropsychiatric disorders and in key phases of typical development. This raises
      the question whether these similar classes of behavior are caused by similar
      neurobiological mechanisms or whether they are neurobiologically unique? In this
      paper we discuss fundamental animal research and translational models. Imbalances
      in corticostriatal function often result in repetitive behavior, where different
      classes of behavior appear to be supported by similar neural mechanisms. Although
      the exact nature of these imbalances are not yet fully understood, synthesizing
      the literature in this area provides a framework for studying the neurobiological
      systems involved in repetitive behavior.

PMID- 20156481
TI  - Mycobacterium vaccae vaccine to prevent tuberculosis in high risk people: a meta
      analysis.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of Mycobacterium vaccae (MV)
      in prevention of tuberculosis (TB) among high risk people. METHODS: Database of
      MEDLINE, EMBASE, BIOSIS, SCI, Cochrane Central Register of Controlled Trials,
      CBM, CNKI and VIP were searched till July 2009. Randomized controlled trials
      (RCTs) or non-randomized controlled clinical trials (CCTs) investigating MV as
      interventions in people at high risk of TB were identified for critical
      appraisal. Two reviewers independently performed data extraction and quality
      assessment. Effectiveness of MV was summarized in different group of risk people
      through RevMan 5.0 by The Cochrane Collaboration. RESULTS: Thirteen studies were
      included. Risk difference (RD) of protection index (PI), its 95% confidence
      interval (95%CI) and the P value were as following: MV vs. Isoniazid (INH): 0.02
      (-0.01, 0.05) (P=0.12); MV vs. (INH plus RFT): 0.00 (-0.00, 0.00) (P=1.00); MV
      vs. Blank: 0.04 (0.00, 0.08) (P=0.03) for soldiers with PPD strong positive; 0.00
      (-0.00, 0.00) (P=0.05) for students with PPD strong positive; 0.20 (0.05, 0.36)
      (P=0.01) for aged people of clinical cured pulmonary TB, and 0.08 (0.01, 0.14)
      (P=0.03) for type 2 diabetes mellitus. In HIV-infected people, The Risk Ratio
      (RR) of MV vs. CV (control vaccine) of positive stimulation index (SI) (> or = 3)
      in lymphocyte proliferation assays (LPA) to Mycobacterium vaccae sonicate (MVS)
      was 2.39 with 95% CI (1.56, 3.66), P<0.0001. Immunization had no adverse effects
      on CD4 cell count or HIV viral load. The most frequent adverse effects of MV were
      induration and sore arm. CONCLUSIONS: Available evidence shows that MV is
      effective in preventing TB in PPD strong positive/type 2 diabetes mellitus/aged
      people of clinical cured pulmonary TB, and is safe, well-tolerated and effective
      in inducing biologically relevant immune response against TB in HIV-infected
      patients. High-quality trials aimed at different groups of high risk people are
      encouraged.

PMID- 20156482
TI  - Impacts of recent advances in cardiovascular regenerative medicine on clinical
      therapies and drug discovery.
AB  - Although stem-cell technology holds great promise for the treatment of
      degenerative diseases and the development of new drugs, progress has been
      hindered by immune and ethical problems in association with the use of embryonic
      stem cells (ESCs). The recent development of reprogramming of differentiated
      human somatic cells to pluripotent stem cells (iPSCs) should overcome these
      obstacles and facilitate clinical applications of stem cells. One of the
      advantages of reprogramming is that it allows the establishment of patient- and
      disease-specific in vitro models of human hereditary diseases for
      pathophysiologic and developmental studies. These in vitro models can be used for
      drug development and testing, moving us a step closer to personalized therapies.
      This review outlines the current status of pluripotent stem cells and focuses on
      the potential applications of stem cell-derived cardiomyocytes for clinical
      therapies, as well as for drug development and testing.

PMID- 20156483
TI  - A near-infrared calibration method suitable for quantification of broadband data
      in humans.
AB  - Broadband near-infrared spectroscopy (bNIRS) is a powerful non-invasive technique
      for the measurement of hemoglobin. bNIRS systems are relatively simple to
      construct compared with many near-infrared instruments since they operate on the
      principle of continuous wave. The advantage of the broadband method is the
      capacity to model the spectra and to use "the second differential method" to
      quantify deoxyhemoglobin (HHb). An "anoxia pulse" method can be applied to
      quantify total haemoglobin (tHb) and tissue oxygen saturation (S(t)O(2)). A
      disadvantage is that this calibration method is not suitable for application in
      humans. In this study, we compared the "anoxia pulse" method with "graded
      hypoxia" method, which can be applied for human studies, to quantify tHb and
      S(t)O(2). The values obtained with the two methods were respectively (tHb=47.8+/
      2.8 and 49.4+/-7.7 microM, mean+/-S.D., n=8) and (S(t)O(2)=72.8+/-3.7% and 73.2+/
      5.7%, mean+/-S.D., n=8). There was no significant difference (p<0.05) between the
      two methods, indicating that the graded hypoxia method could be used for
      quantification of tHb and S(t)O(2) in human subjects.

PMID- 20156484
TI  - TXNIP regulates germinal center generation by suppressing BCL-6 expression.
AB  - The detailed mechanism driving the germinal center (GC) reaction to B cell
      lymphomagenesis has not been clarified. Thioredoxin interacting protein (TXNIP),
      also known as vitamin D3 up-regulated protein 1 which is an important tumor
      repressor, is involved in stress responses, redox regulation, and cellular
      proliferation. Here, we report that TXNIP has a potential role in the formation
      of GC in peripheral lymphoid organs where B lymphocytes divide rapidly. First, we
      compared changes in GC from wild type mice and Txnip(-/-) mice. After
      immunization, Txnip(-/-) mice exhibited higher expression level of BCL-6 and
      larger percentage of GC B cells with the reduction in antibody production and
      plasma cell numbers. In addition, Txnip(-/-) spleens had a much larger population
      which expressed Ki-67, a marker of cell proliferation, in the red pulp border
      than WT spleens. Furthermore, the expression of BCL-6 was decreased in TXNIP
      overexpressing cells and elevated in TXNIP deficient cells. Taken together, we
      conclude that TXNIP may contribute to the formation of GCs after immunization.
      During this process, TXNIP suppresses BCL-6 expression.

PMID- 20156485
TI  - A peptide derived from hepatitis C virus E2 envelope protein inhibits a post
      binding step in HCV entry.
AB  - The HCV envelope proteins E1 and E2 are required for virus binding to cellular
      receptors and pH-dependent fusion with endosomal membranes. Envelope protein
      interactions within this multistep process may provide novel targets for
      development of antiviral agents. To identify E1 and E2 regions involved in
      critical steps of HCV entry, we screened an E1E2 overlapping peptide library for
      inhibition of infection using a lentiviral reporter vector pseudotyped with E1E2
      envelope proteins. A 16-residue polypeptide containing a portion of the E2
      transmembrane domain (Peptide 75) inhibited HCV pseudoparticle infection with an
      IC50 of approximately 0.3microM and did not inhibit infection by VSV-g
      pseudoparticles at concentrations up to 50microM. Structure-activity analysis of
      Peptide 75 showed that antiviral activity was dependent upon L-configuration and
      hydrophobic character, and that the native sequence was required for maximal
      activity. Peptide 75 did not show virocidal activity against HCV pseudoparticles
      or other viruses. Temperature-shift experiments showed that the peptide acted at
      a post-binding step and that inhibition was further increased when used in
      combination with an anti-CD81 antibody previously shown to inhibit pseudoparticle
      entry at a post-binding step. These data suggest that interactions involving the
      C terminal region of E2 may play an important role in the HCV entry process.

PMID- 20156486
TI  - A novel Hepatitis C virus p7 ion channel inhibitor, BIT225, inhibits bovine viral
      diarrhea virus in vitro and shows synergism with recombinant interferon-alpha-2b
      and nucleoside analogues.
AB  - The novel small molecule, BIT225 (N-[5-(1-methyl-1H-pyrazol-4-yl)-napthalene-2
      carbonyl]-guanidine: CAS No. 917909-71-8), was initially identified using a
      screening strategy designed to detect inhibitors of Hepatitis C virus (HCV) p7
      ion channel activity. Here we report that BIT225 has potent stand-alone antiviral
      activity against the HCV model pestivirus bovine viral diarrhea virus (BVDV) with
      an IC(50) of 314nM. Combinations of BIT225 with recombinant interferon alpha-2b
      (rIFNalpha-2b) show synergistic antiviral action against BVDV and the synergy is
      further enhanced by addition of ribavirin. Synergy was also observed between
      BIT225 and two nucleoside analogues known to inhibit the HCV RNA-dependent RNA
      polymerase. BIT225 has successfully completed a phase Ia dose escalating, single
      dose safety trial in healthy volunteers and a phase Ib/IIa trial to evaluate the
      safety and pharmacokinetics of repeated dosing for selected doses of BIT225 in
      HCV-infected persons. A modest, but statistically significant drop in patient
      viral load was detected over the 7 days of dosing (ref. www.biotron.com.au).
      Given the critical role of the p7 protein in the HCV life cycle and
      pathogenicity, our data indicate that molecules like BIT225, representing a new
      class of antiviral compounds, may be developable for therapeutic use against HCV
      infection, either as monotherapy, or in combination with other HCV drugs.

PMID- 20156487
TI  - Lateralized and sex-dependent behavioral and morphological effects of unilateral
      neonatal cerebral hypoxia-ischemia in the rat.
AB  - Neonatal cerebral hypoxia-ischemia (HI) is an important cause of neurological
      deficits. The Levine-Rice model of unilateral HI is a useful experimental tool,
      but the resulting brain damage is mainly restricted to one hemisphere. Since the
      rat presents morphological and biochemical asymmetries between brain hemispheres,
      behavioral outcome from this model is probably dependent on which hemisphere is
      damaged. We here investigated the effects of sex and lesioned hemisphere on the
      outcome of open field, plus maze, inhibitory avoidance and water maze tasks in
      adult rats previously submitted to neonatal unilateral HI. Females were more
      active than males in some of studied parameters and males presented better
      spatial learning. Hypoxia-ischemia caused spatial deficits independently of sex
      or damaged hemisphere. Right-HI increased locomotion only in males and caused
      working memory in females and on aversive learning in both males and females.
      Morphological analysis showed that right-HI animals presented greater reduction
      of ipsilateral striatum area, with females being more affected. Interestingly,
      males showed greater hippocampal volume. These results show that task performance
      and cerebral damage extension are lateralized and sex-dependent, and that the
      right hemisphere, irrespective of sex, is more vulnerable to neonatal cerebral
      hypoxia-ischemia.

PMID- 20156488
TI  - Dopaminergic dysregulation in mice selectively bred for excessive exercise or
      obesity.
AB  - Dysregulation of the dopamine system is linked to various aberrant behaviors,
      including addiction, compulsive exercise, and hyperphagia leading to obesity. The
      goal of the present experiments was to determine how dopamine contributes to the
      expression of opposing phenotypes, excessive exercise and obesity. We
      hypothesized that similar alterations in dopamine and dopamine-related gene
      expression may underly obesity and excessive exercise, as competing traits for
      central reward pathways. Moreover, we hypothesized that selective breeding for
      high levels of exercise or obesity may have influenced genetic variation
      controlling these pathways, manifesting as opposing complex traits. Dopamine,
      dopamine-related peptide concentrations, and gene expression were evaluated in
      dorsal striatum (DS) and nucleus accumbens (NA) of mice from lines selectively
      bred for high rates of wheel running (HR) or obesity (M16), and the non-selected
      ICR strain from which these lines were derived. HPLC analysis showed
      significantly greater neurotransmitter concentrations in DS and NA of HR mice
      compared to M16 and ICR. Microarray analysis showed significant gene expression
      differences between HR and M16 compared to ICR in both brain areas, with changes
      revealed throughout the dopamine pathway including D1 and D2 receptors,
      associated G-proteins (e.g., Golf), and adenylate cyclase (e.g., Adcy5). The
      results suggest that similar modifications within the dopamine system may
      contribute to the expression of opposite phenotypes in mice, demonstrating that
      alterations within central reward pathways can contribute to both obesity and
      excessive exercise.

PMID- 20156489
TI  - Prepuberal subchronic methylphenidate and atomoxetine induce different long-term
      effects on adult behaviour and forebrain dopamine, norepinephrine and serotonin
      in Naples high-excitability rats.
AB  - The psychostimulant methylphenidate and the non-stimulant atomoxetine are two
      approved drugs for attention-deficit hyperactivity disorder (ADHD) therapy. The
      aim of this study was to investigate the long-term effects of prepuberal
      subchronic methylphenidate and atomoxetine on adult behaviour and the forebrain
      neurotransmitter and metabolite content of Naples High-Excitability (NHE) rats, a
      genetic model for the mesocortical variant of ADHD. Male NHE rats were given a
      daily intraperitoneal injection (1.0mg/kg) of methylphenidate, atomoxetine or
      vehicle from postnatal day 29 to 42. At postnatal day 70-75, rats were exposed to
      spatial novelty in the Lat and radial (Olton) mazes. Behavioural analysis for
      indices of horizontal, vertical, non-selective (NSA) and selective spatial
      attention (SSA) indicated that only methylphenidate significantly reduced
      horizontal activity to a different extent, i.e., 39 and 16% respectively.
      Moreover methylphenidate increased NSA as assessed by higher leaning duration.
      The high-performance liquid chromatography (HPLC) tissue content assessment of
      dopamine, norepinephrine, serotonin and relative metabolites in the prefrontal
      cortex (PFC), cortical motor area (MC), dorsal striatum (DS), ventral striatum
      (VS), hippocampus and mesencephalon indicated that methylphenidate decreased (i)
      dopamine, DOPAC, norepinephrine, MHPG, 5-HT and 5-HIAA in the PFC, (ii) dopamine,
      DOPAC, HVA, serotonin, 5-HIAA in the DS, (iii) dopamine, DOPAC, HVA and MHPG (but
      increased norepinephrine) in the VS and (iv) norepinephrine, MHPG, serotonin and
      5-HIAA in the hippocampus. Atomoxetine increased dopamine and decreased MHPG in
      the PFC. Like methylphenidate, atomoxetine decreased dopamine, DOPAC, HVA,
      serotonin and 5-HIAA in the DS, but decreased MHPG in the VS. These results
      suggest that methylphenidate determined long-term effects on behavioural and
      neurochemical parameters, whereas atomoxetine affected only the latter.

PMID- 20156490
TI  - A population of tRNA-derived small RNAs is actively produced in Trypanosoma cruzi
      and recruited to specific cytoplasmic granules.
AB  - Over the last years an expanding family of small RNAs (i.e. microRNAs, siRNAs and
      piRNAs) was recognized as key players in diverse forms of gene silencing and
      chromatin organization. Effectors functions of these small RNAs are achieved
      through ribonucleoprotein (RNP) complexes containing at their center an
      Argonaute/Piwi protein. Although these proteins and their small RNA-associated
      machinery can be traced back to the common ancestor of eukaryotes, this machinery
      seems to be entirely lost or extensively simplified in some unicellular organisms
      including Trypanosoma cruzi, which are unable to trigger RNAi related phenomena.
      Speculating about the presence of alternate small RNA-mediated pathways in these
      organisms, we constructed and analyzed a size-fractionated cDNA library (20-35
      nt) from epimastigotes forms of T. cruzi. Our results showed the production of an
      abundant class of tRNA-derived small RNAs preferentially restricted to specific
      isoacceptors and whose production was more accentuated under nutritional stress.
      These small tRNAs derived preferentially from the 5' halves of mature tRNAs and
      were recruited to distinctive cytoplasmic granules. Our data favor the idea that
      tRNA cleavage is unlikely to be the consequence of non-specific degradation but a
      controlled process, whose biological significance remains to be elucidated.

PMID- 20156491
TI  - Relaxing the coenzyme specificity of 1,3-propanediol oxidoreductase from
      Klebsiella pneumoniae by rational design.
AB  - 1,3-Propanediol has wide applications for large volume markets, particularly in
      the polymer business. Microbial production of 1,3-propanediol has been considered
      as a competitor to the traditional petrochemical routes. However, the formation
      of 1,3-propanediol is limited by the amount of NADH supplied by the oxidative
      pathway of glycerol dismutation. Previous metabolic flux analysis revealed that
      relaxation of the coenzyme specificity of 1,3-propanediol oxidoreductase for both
      NADH and NADPH would increase the production of 1,3-propanediol as well as
      maintaining the NADH-NAD(+) circle. This work tried to accomplish such a
      relaxation by rational protein design. Overall binding free energy indicated that
      the electrostatic energy was the major force discriminating NADH from NADPH.
      Computational alanine-scanning mutagenesis of the active site residues
      illustrated that Asp41 was the key residue responsible for the coenzyme
      specificity. Compared with Asp41Ala, Asp41Gly could further weaken the repulsion
      between Asp41 and the phosphate group esterified to the 2'-hydroxyl group of the
      ribose at the adenine end of NADPH. Site-directed mutagenesis was conducted and
      the relaxation was successfully realized.

PMID- 20156492
TI  - Influence of ammonium on the accumulation of polyhydroxybutyrate (PHB) in aerobic
      open mixed cultures.
AB  - Mixed microbial cultures enriched in feast-famine sequencing batch reactors
      (SBRs) can accumulate large amounts of the bioplastic PHB under conditions of
      ammonium starvation. If waste streams are to be used as a substrate, nutrient
      starvation may not always be achievable. The aim of this study was to investigate
      the influence of ammonium on PHB production in the PHB production stage of the
      process. The biomass was enriched in an acetate-fed (carbon limited) feast-famine
      SBR operated at 30 degrees C, 1-d sludge residence time and with a cycle length
      of 12h. The biomass was used in three fed-batch experiments with medium C/N
      ratios of infinity (ammonium starvation), 40 Cmol Nmol(-1) (ammonium limitation)
      and 8 Cmol Nmol(-1) (ammonium excess) and acetate as the carbon source. Under
      conditions of ammonium starvation the biomass reached a maximum PHB content of 89
      wt% after 7.6h, under ammonium limitation 77 wt% after 9.3h and under ammonium
      excess 69 wt% after 4.4h. PHB contents decreased after these maxima were reached.
      PHB production slowed down more with time with larger ammonium availability.
      Growth led to a dilution of the PHB pool after the maximum PHB content was
      reached. Nutrient starvation seems thus to be the best strategy for maximal PHB
      production.

PMID- 20156493
TI  - Gene expression density profiles characterize modes of genomic regulation: theory
      and experiment.
AB  - Our study addresses modes of genomic regulation and their characterization using
      the distribution of expression values. A simple model of transcriptional
      regulation is introduced to characterize the response of the global expression
      pattern to the changing properties of basal regulatory building blocks. Random
      genomes are generated which express and bind transcription factors according to
      the appearance of short motifs of coding and binding sequences. Regulation of
      transcriptional activity is described using a thermodynamic model. Our model
      predicts single-peaked distributions of expression values the flanks of which
      decay according to power laws. The characteristic exponent is inversely related
      to the product of the connectivity of the network times the regulatory strength
      of bound transcription factors. Such 'expression spectra' were calculated and
      analyzed for different model genomes. Information on structural properties and on
      the interactions of regulatory elements is used to build up a framework of basic
      characteristics of expression spectra. We analyze examples addressing different
      biological issues. Peak position and width of the experimental expression spectra
      vary with the biological context. We demonstrate that the study of the global
      expression pattern provides valuable information about transcriptional regulation
      which complements conventional searches for differentially expressed single
      genes.

PMID- 20156494
TI  - Optimised mammalian expression through the coupling of codon adaptation with gene
      amplification: maximum yields with minimum effort.
AB  - Gene amplification methodologies are frequently employed for the generation of
      large quantities of recombinant proteins in mammalian cells. Although they
      usually guarantee very high yields, they are very time consuming. In addition,
      due to the large genomic re-arrangements that frequently occur with
      amplification, the resulting high-producing clones can be unstable. We herein
      describe significant improvements to the dihydrofolate reductase
      (DHFR)/methotrexate (MTX) based gene amplification methodology typically employed
      to improve yields of recombinant proteins produced in genetically engineered CHO
      host cells. We demonstrate substantial synergy when such gene amplification is
      combined with extremely high codon optimisation strategies. As a result,
      expression saturation can be achieved rapidly, in as low as 5 nM MTX, with
      minimal effort and without compromise in final yields achieved.

PMID- 20156495
TI  - High level expression of a hydrophobic poly(ethylene terephthalate)-hydrolyzing
      carboxylesterase from Thermobifida fusca KW3 in Escherichia coli BL21(DE3).
AB  - The gram-positive thermophilic actinomycete Thermobifida fusca KW3 secretes a
      highly hydrophobic carboxylesterase (TfCa) that is able to hydrolyze
      poly(ethylene terephthalate). TfCa was produced in the Escherichia coli strain
      BL21(DE3) as a fusion protein consisting of a pelB leader sequence to ensure
      periplasmic localization of the protein and a His(6) tag for use in its
      purification. To enhance the recombinant enzyme yield, the tfca gene from T.
      fusca KW3 was successfully optimized for codon usage in E. coli. In addition, the
      gene expression induction conditions were optimized and the temperature for cell
      cultivation was lowered to reduce inclusion body formation. The optimized codons
      and expression conditions yielded 4500-fold higher TfCa activity than the wild
      type strain. Using a pH-controlled bioreactor for cultivation, a TfCa protein
      concentration of 41.6mg/L was achieved.

PMID- 20156496
TI  - Complete nucleic acid sequence of Penaeus monodon densovirus (PmDNV) from India.
AB  - The complete nucleic acid sequence of the Penaeus monodon densovirus (PmDNV) from
      India was characterized. Analysis of the whole genome, consisting of 6310 bp
      revealed the presence of three open reading frames (ORFs), comprising 1281 bp,
      1734 bp and 2460 bp, respectively. The complete genome and amino acid sequences
      of three proteins viz., NS1, NS2 and VP were compared with PmDNV from Thailand,
      PmergDNV from Australia and other partial sequences in GenBank, respectively.
      Highest nucleotide similarity was observed with the Thai strain (88%), while 33,
      32 and 91 amino acid substitutions were observed in the NS2, NS1 and VP,
      respectively. Phylogenetic analysis of shrimp, insect and vertebrate parvovirus
      sequences revealed that the Indian PmDNV is more closely related to Thai isolates
      than all other parvoviruses reported so far.

PMID- 20156497
TI  - Targeted PLGA nano- but not microparticles specifically deliver antigen to human
      dendritic cells via DC-SIGN in vitro.
AB  - Vaccine efficacy is strongly enhanced by antibody-mediated targeting of vaccine
      components to dendritic cells (DCs), which are professional antigen presenting
      cells. However, the options to link antigens or immune modulators to a single
      antibody are limited. Here, we engineered versatile nano- and micrometer-sized
      slow-release vaccine delivery vehicles that specifically target human DCs to
      overcome this limitation. The nano- (NPs) and microparticles (MPs), with
      diameters of approximately 200nm and 2microm, consist of a PLGA core coated with
      a polyethylene glycol-lipid layer carrying the humanized targeting antibody hD1,
      which does not interact with complement or Fc receptors and recognizes the human
      C-type lectin receptor DC-SIGN on DCs. We studied how these particles interact
      with human DCs and blood cells, as well as the kinetics of PLGA-encapsulated
      antigen degradation within DCs. Encapsulation of antigen resulted in almost 38%
      degradation for both NPs and MPs 6days after particle ingestion by DCs, compared
      to 94% when nonencapsulated, soluble antigen was used. In contrast to the MPs,
      which were taken up rather nonspecifically, the NPs effectively targeted human
      DCs. Consequently, targeted delivery only improved antigen presentation of NPs
      and induced antigen-dependent T cell responses at 10-100 fold lower
      concentrations than nontargeted NPs.

PMID- 20156499
TI  - Nanomaterials for in situ cell delivery and tissue regeneration.
AB  - Nanomaterials can be defined as materials that possess clearly defined features
      of less than 100nm, and whose nanostructured features confer characteristics
      crucial to the material's bulk property. The nanostructured features can be an
      intermediate or final state of the material in its synthesis process. The field
      of nanomaterials as applied to in situ cell delivery and tissue engineering is
      rapidly expanding. Nanomaterials that include peptide amphiphiles, self
      assembling peptides, electrospun scaffolds, layer-by-layer complexes, nanotubes
      and nanocomposites have been applied to cell culture, encapsulation and delivery
      with promising results. As compared to scaffold-free cell delivery, nanomaterials
      are advantageous in terms of providing a means to control the biochemical and
      mechanical microenvironment of the cells. Nanomaterials are amenable to a bottom
      up approach in functionalization and mechanical tuning, as illustrated in the
      examples presented in this review. Furthermore, nanomaterials such as DNA
      polyplexes and carbon nanotubes can also be incorporated into the cell delivery
      vehicle to improve the regenerative outcome. Lastly, while nanomaterials harbor
      much potential for cell delivery and tissue regeneration, further
      characterization is required in terms of clinical safety before these materials
      can be employed towards therapeutic applications.

PMID- 20156498
TI  - Optically guided controlled release from liposomes with tunable plasmonic
      nanobubbles.
AB  - A new method of optically guided controlled release was experimentally evaluated
      with liposomes containing a molecular load and gold nanoparticles (NPs). NPs were
      exposed to short laser pulses to induce transient vapor bubbles around the NPs,
      plasmonic nanobubbles, in order to disrupt the liposome and eject its molecular
      contents. The release efficacy was tuned by varying the lifetime and size of the
      nanobubble with the fluence of the laser pulse. Optical scattering by nanobubbles
      correlated to the molecular release and was used to guide the release. The
      release of two fluorescent proteins from individual liposomes has been directly
      monitored by fluorescence microscopy, while the generation of the plasmonic
      nanobubbles was imaged and measured with optical scattering techniques. Plasmonic
      nanobubble-induced release was found to be a mechanical, nonthermal process that
      requires a single laser pulse and ejects the liposome contents within a
      millisecond timescale without damage to the molecular cargo and that can be
      controlled through the fluence of laser pulse.

PMID- 20156500
TI  - Substitution of healthy for unhealthy beverages among college students. A health
      concerns and behavioral-economics perspective.
AB  - Excessive intake of sugar-sweetened beverages by undergraduates is closely
      related to the increasing prevalence of obesity, making investigations of the
      substitution of healthy for unhealthy beverages imperative. According to the
      concept of price elasticity in behavioral economics, the choice of healthy over
      unhealthy behaviors is facilitated by increasing the cost of less-healthy
      alternatives or reducing the cost of healthier alternatives. Furthermore, evoking
      health concerns by using health claims may induce substitution of healthy for
      unhealthy beverages. A total of 108 18-22-year-old undergraduates participated in
      a laboratory experiment and were given a certain amount of money and allowed to
      purchase a healthy beverage and a less-healthy beverage with or without receiving
      health claims. Increasing the price of a type of beverage was shown to reduce
      purchases of that beverage type and lead to substitution with the alternative
      type. Moreover, the effect of price elasticity on healthy beverage substitution
      was more pronounced when participants' health concerns were evoked. The results
      suggest that lowering the cost of alternative commodities and evoking health
      concerns by health-related claims would foster the substitution of healthier for
      unhealthy beverages among college students.

PMID- 20156501
TI  - Microinjection of neuropeptide S into the rat ventral tegmental area induces
      hyperactivity and increases extracellular levels of dopamine metabolites in the
      nucleus accumbens shell.
AB  - The newly identified neuropeptide S (NPS) is mainly expressed in a group of
      neurons located between the locus coeruleus and Barrington's nucleus in the
      brainstem. Central administration of NPS increases motor activity and
      wakefulness, and it decreases anxiety-like behavior and feeding. The NPS receptor
      (NPSR) is widely distributed in various brain regions including the ventral
      tegmental area (VTA). The mesolimbic dopaminergic system originates in the VTA,
      and activation of the system produces hypermotor activity. Therefore, we
      hypothesized that NPS-induced hypermotor activity might be mediated by activation
      of the mesolimbic dopaminergic pathway via the NPSR expressed in the VTA. Intra
      VTA injection of NPS significantly and dose-dependently increased horizontal and
      vertical motor activity in rats, and the hyperactivity was significantly and dose
      dependently inhibited by pre-administration of sulpiride, a DA D(2)-like receptor
      antagonist, into the shell of the nucleus accumbens (NAcSh). Intra-VTA injection
      of NPS also significantly increased extracellular 3,4-dihydroxy-phenyl acetic
      acid and homovanillic acid levels in the NAcSh of freely moving rats. These
      results support the idea that NPS activates the mesolimbic dopaminergic system
      presumably via the NPSR located in the VTA, thereby stimulating motor activity.

PMID- 20156502
TI  - Regulation of beta-cell viability and gene expression by distinct agonist
      fragments of adiponectin.
AB  - Obesity is an established risk factor for type 2 diabetes. Activation of the
      adiponectin receptors has a clear role in improving insulin resistance although
      conflicting evidence exists for its effects on pancreatic beta-cells. Previous
      reports have identified both adiponectin receptors (ADR-1 and ADR-2) in the beta
      cell. Recent evidence has suggested that two distinct regions of the adiponectin
      molecule, the globular domain and a small N-terminal region, have agonist
      properties. This study investigates the effects of two agonist regions of
      adiponectin on insulin secretion, gene expression, cell viability and cell
      signalling in the rat beta-cell line BRIN-BD11, as well as investigating the
      expression levels of adiponectin receptors (ADRs) in these cells. Cells were
      treated with globular adiponectin and adiponectin (15-36) +/-leptin to
      investigate cell viability, expression of key beta-cell genes and ERK1/2
      activation. Both globular adiponectin and adiponectin (15-36) caused significant
      ERK1/2 dependent increases in cell viability. Leptin co-incubation attenuated
      adiponectin (15-36) but not globular adiponectin induced cell viability. Globular
      adiponectin, but not adiponectin (15-36), caused a significant 450% increase in
      PDX-1 expression and a 45% decrease in LPL expression. ADR-1 was expressed at a
      higher level than ADR-2, and ADR mRNA levels were differentially regulated by non
      esterified fatty acids and peroxisome-proliferator-activated receptor agonists.
      These data provide evidence of roles for two distinct adiponectin agonist domains
      in the beta-cell and confirm the potentially important role of adiponectin
      receptor agonism in maintaining beta-cell mass.

PMID- 20156503
TI  - Involvement of endothelin B receptors in the endothelin-3-induced increase of
      ghrelin and growth hormone in Holstein steers.
AB  - The present study was designed to determine the dose-dependent effects of
      endothelin-3 (ET-3) on the secretion of ghrelin and growth hormone (GH) and
      characterize the receptors involved in these effects. Eight Holstein steers were
      randomly assigned to receive intravenous bolus injections of vehicle (0.1% bovine
      serum albumin in saline), bovine ET-3 (0.1, 0.4, 0.7 and 1.0microg/kg), IRL1620
      (selective ET(B) receptor agonist, 2.0microg/kg), [d-Lys(3)]-GHRP-6 (GH
      secretagogue receptor type 1a [GHS-R1a] antagonist, 20.0microg/kg) and bovine ET
      3 (1.0microg/kg) combined with [d-Lys(3)]-GHRP-6 (20.0microg/kg), respectively.
      Blood samples were collected at -30, -15, 0, 5, 10, 15, 20, 25, 30, 35, 40, 50
      and 60min relative to injection time. Concentrations of acyl ghrelin, total
      ghrelin (acyl and des-acyl ghrelin) and GH in plasma were analyzed by a double
      antibody radioimmunoassay system. Concentrations of acyl and total ghrelin were
      significantly increased by ET-3 in a dose-dependent manner. Concentrations of GH
      were markedly elevated by administration of 0.4, 0.7 and 1.0microg/kg of ET-3,
      and the effect of 0.7microg/kg was greater than that of 1.0microg/kg. The minimum
      effective dose of ET-3 in the secretion of ghrelin and GH was 0.4microg/kg. IRL
      1620 mimicked the effects of ET-3 on the secretion of ghrelin and GH in plasma.
      ET-3-induced elevation of plasma GH was blocked by [d-Lys(3)]-GHRP-6. These
      results indicate that ET-3 dose-dependently stimulates ghrelin release, and ET(B)
      receptors involve in these processes. Moreover, this study shows that endogenous
      ghrelin response to ET-3 increases GH secretion through GHS-R1a.

PMID- 20156505
TI  - Role of the C8orf13-BLK region in biopsy-proven giant cell arteritis.
AB  - Giant cell arteritis (GCA) is a complex polygenic disease in which more than one
      genetic locus is likely to contribute to disease susceptibility and clinical
      expression. In the present study, we have analyzed for first time the implication
      of rs13277113 and rs2736340 variants from the C8orf13-BLK gene region in the
      susceptibility to GCA. A total of 220 biopsy-proven GCA patients and 486 matched
      controls were assessed. DNA from patients and controls was obtained from
      peripheral blood. Samples were genotyped for the C8orf13-BLK region rs13277113
      and rs2736340 using a predesigned TaqMan allele discrimination assay. No
      significant differences in the genotype distribution between GCA patients and
      controls for the rs13277113 and rs2736340 C8orf13-BLK gene variants were found.
      GCA patients were also stratified according to the presence of specific clinical
      features of the disease. In this regard, the allele A of the rs13277113 variant
      was overrepresented in patients with severe ischemic manifestations compared with
      patients without severe ischemic manifestations (p = 0.04; OR =1.65; 95% CI =
      0.99-2.78). In conclusion, our results do not support a major implication of the
      C8orf13-BLK gene region in susceptibility to GCA. However, a potential
      implication of the rs13277113 variant in the development of severe ischemic
      complications may exist.

PMID- 20156504
TI  - Regulated exocytosis in astrocytic signal integration.
AB  - Astrocytes can be considered as signal integrators in central nervous system
      activity. These glial cells can respond to signals from the heterocellular milieu
      of the brain and subsequently release various molecules to signal to themselves
      and/or other neighboring neural cells. An important functional module that
      enables signal integration in astrocytes is exocytosis, a Ca(2+)-dependent
      process consisting of vesicular fusion to the plasma membrane. Astrocytes utilize
      regulated exocytosis to release various signaling molecules stored in the
      vesicular lumen. Here we review the properties of exocytotic release of three
      classes of gliotransmitters: (i) amino acids, (ii) nucleotides and (iii)
      peptides. Vesicles may carry not only lumenal cargo, but also membrane-associated
      molecules. Therefore, we also discuss exocytosis as a delivery mechanism for
      transporters and receptors to the plasma membrane, where these proteins are
      involved in astrocytic intercellular signaling.

PMID- 20156506
TI  - Identification of broad binding class I HLA supertype epitopes to provide
      universal coverage of influenza A virus.
AB  - Influenza virus remains a significant health concern, with current circulating
      strains that affect millions each year plus the threat of newly emerging strains,
      such as swine-origin H1N1 and avian H5N1. Our hypothesis is that influenza
      derived HLA-class I-restricted epitopes can be identified for use as a reagent to
      monitor and quantitate human CD8(+) T-cell responses and for vaccine development
      to induce protective cellular immunity. Protein sequences from influenza A virus
      strains currently in circulation, agents of past pandemics and zoonotic
      infections of man were evaluated for sequences predicted to bind to alleles
      representative of the most frequent HLA-A and -B (class I) types worldwide.
      Peptides that bound several different HLA molecules and were conserved among
      diverse influenza subtypes were tested for their capacity to recall influenza
      specific immune responses using human donor PBMC. Accordingly, 28 different
      epitopes antigenic for human donor PBMC were identified and 25 were 100%
      conserved in the newly emerged swine-origin H1N1 strain. The epitope set defined
      herein should provide a reagent applicable to quantitate CD8(+) T cell human
      responses irrespective of influenza subtype and HLA composition of the responding
      population. In addition, these epitopes may be suitable for vaccine applications
      directed at the induction of cellular immunity.

PMID- 20156507
TI  - New HLA class I epitopes defined by murine monoclonal antibodies.
AB  - This study defines 10 epitopes by murine monoclonal antibodies, of which seven
      are new and three were previously defined by alloantibodies. Of particular
      interest, three antibodies reacted with almost all Bw4-associated antigens except
      that each was negative with one or two of the antigens. One was negative with
      B13, one negative with A25, and another negative with B13 & A24 antigens. These
      monoclonal antibodies exhibited reactivity contrary to Bw4 allosera, which
      typically react with all Bw4-associated antigens. All monoclonal antibodies were
      tested with a panel of 97 human leukocyte antigen (HLA) class I (A, B, and
      Clocus) rHLA single antigens (SA) individually coupled to different microsphere
      beads. Identifying HLA antigens sharing distinct epitopes can be helpful when
      selecting patient-donor transplantation pairs, explaining antibodies against rare
      specificities, or against non-donor-specific antigens (NDSA). This study adds
      seven new HLA class I epitopes to 103 already defined epitopes and provides more
      evidence that a monoclonal antibody and alloantibody can target the same epitope.
      The fact that mAbs can target the same epitopes targeted by allosera, makes mAbs
      useful in studies of cross-reactivity in HLA.

PMID- 20156508
TI  - Phenotypic and clinical heterogeneity associated with monoallelic TNFRSF13B-A181E
      mutations in common variable immunodeficiency.
AB  - Mutations in the TNFRSF13B (TACI) gene have been reported to be associated with
      Common Variable ImmunoDeficiency (CVID). Of 48 patients evaluated within the
      immunodeficiency clinic, 39 had CVID, 6 had symptomatic IgA deficiency (IgAD)
      with or without IgG2 and IgG4 subclass deficiency, while 3 had unclassified
      immune dysregulatory disorders. In all 48 patients TACI genetic testing was
      performed, and monoallelic mutations were observed in 4 of the 39 CVID patients
      (10.26%), an incidence comparable to other studies. Of the 6 IgAD patients, 1 had
      a heterozygous TACI mutation (16.67%), while of the 3 unclassified patients, 1
      had a monoallelic TACI mutation (33.3%), but his sibling who also had the same
      mutation had CVID. The A181E mutation is one of the statistically significant,
      among the known TACI gene mutations. Here, 5 of the 6 patients were found to have
      the A181E mutation (10.42%), which is higher than previously observed. We also
      evaluated 114 controls and found the A181E mutation in only 1 individual (0.88%).
      We report in this study that the A181E mutation is associated with a very
      heterogeneous clinical presentation along with variability in B-cell numbers and
      amount of TACI protein on memory B cells.

PMID- 20156509
TI  - Gene expression profiling of the donor kidney at the time of transplantation
      predicts clinical outcomes 2 years after transplantation.
AB  - We have previously demonstrated that biomarkers of inflammation and immune
      activity detected within intraoperative renal transplant allograft biopsies are
      linked to adverse short-term post-transplantation clinical outcomes. Now we
      provide a post hoc analysis of our earlier data in the light of longer clinical
      follow-up. A total of 75 consecutively performed renal allografts were analyzed
      for gene expression of proinflammatory molecules, inflammation-induced adhesion
      molecules, and antiapoptotic genes expressed 15 minutes after vascular
      reperfusion to determine whether this analysis can aid in predicting long-term
      quality of renal function, proteinuria, graft loss, and death-censored graft. We
      have built predictive models for proteinuria (area under the curve = 0.859, p =
      0.0001) and graft loss (area under the curve = 0.724, p = 0.027) 2 years post
      transplantation using clinical variables in combination with intragraft gene
      expression data of tumor necrosis factor-alpha, interleukin-6, CD40, CD3, and
      tumor necrosis factor-alpha, Bcl-2, and interferon-gamma, respectively. This post
      hoc analysis demonstrates that hypothesis-driven, targeted polymerase chain
      reaction profiling of gene expression in the donor kidney at the time of
      engraftment can predict 2-year post-transplantation clinical outcomes.

PMID- 20156510
TI  - Prognostic relevance of soluble human leukocyte antigen-G and total human
      leukocyte antigen class I molecules in lung cancer patients.
AB  - The aim of this study was to determine the prognostic significance of soluble
      human leukocyte antigen (HLA) class I (sHLA-I) and HLA-G molecules in lung cancer
      patients. A total of 23 small-cell lung cancer (SCLC) and 114 non-small-cell lung
      cancer (NSCLC) patients, including 55 adenocarcinoma, 46 squamous cell carcinoma
      (SCC), and 13 patients with undifferentiated carcinoma, were prospectively
      enrolled. Levels of sHLA-G and sHLA-I were analyzed by specific enzyme-linked
      immunosorbent assay. Median levels of sHLA-G and sHLA-I were significantly
      increased in patients compared with controls (34 ng/ml [3.6-160] vs 14 ng/ml [0
      98], p < 0.0001; 2580 ng/ml [749-5770] vs 1370 ng/ml [274-2670], p < 0.0001,
      respectively). Regarding the different subgroups, patients with NSCLC or SCLC
      showed increased sHLA-I levels, whereas sHLA-G was exclusively elevated in NSCLC,
      especially in patients with SCC. Patients with sHLA-I<2800 ng/ml (p = 0.008) or
      sHLA-G<40 ng/ml (p = 0.073) showed prolonged overall survival (OS). Using these
      cut-offs in patients with SCC, a pronounced prognostic significance for sHLA-G (p
      = 0.003) and sHLA-I (p = 0.004) was observed for the prediction of OS. Here,
      multivariate analysis confirmed sHLA-G and sHLA-I in addition to disease stage as
      independent prognostic factors. The prognostic power was further enhanced by
      combining the two factors and comparing the OS of patients with low sHLA-I and
      low sHLA-G against the remaining ones. In conclusion, plasma levels of sHLA-G and
      sHLA-I are potent predictors for OS in lung cancer patients.

PMID- 20156511
TI  - Towards optimization of chemical testing under REACH: a Bayesian network approach
      to Integrated Testing Strategies.
AB  - Integrated Testing Strategies (ITSs) are considered tools for guiding resource
      efficient decision-making on chemical hazard and risk management. Originating in
      the mid-nineties from research initiatives on minimizing animal use in toxicity
      testing, ITS development still lacks a methodologically consistent framework for
      incorporating all relevant information, for updating and reducing uncertainty
      across testing stages, and for handling conditionally dependent evidence. This
      paper presents a conceptual and methodological proposal for improving ITS
      development. We discuss methodological shortcomings of current ITS approaches,
      and we identify conceptual requirements for ITS development and optimization.
      First, ITS development should be based on probabilistic methods in order to
      quantify and update various uncertainties across testing stages. Second,
      reasoning should reflect a set of logic rules for consistently combining
      probabilities of related events. Third, inference should be hypothesis-driven and
      should reflect causal relationships in order to coherently guide decision-making
      across testing stages. To meet these requirements, we propose an information
      theoretic approach to ITS development, the "ITS inference framework", which can
      be made operational by using Bayesian networks. As an illustration, we examine a
      simple two-test battery for assessing rodent carcinogenicity. Finally, we
      demonstrate how running the Bayesian network reveals a quantitative measure of
      Weight-of-Evidence.

PMID- 20156512
TI  - Screening-level population risk assessment of nasal tumors in the US due to
      naphthalene exposure.
AB  - Several naphthalene Unit Risk Factors (URFs) were proposed by the US
      Environmental Protection Agency in 2004 using data on the development of
      olfactory epithelial neuroblastomas and nasal respiratory epithelial adenomas in
      rats, but these URFs may be inappropriate and unnecessarily conservative for
      estimating human cancer risks. The purpose of the present exercise was to perform
      a screening-level population risk assessment of the US population to compare the
      observed number of naphthalene-induced nasal tumors in the US to the number that
      would be predicted if the URFs for naphthalene were as proposed. Nine scenarios
      were evaluated to represent the range of exposures individuals have typically
      experienced. Results indicate that the total predicted burden of naphthalene
      induced nasal tumors per year in the US (65,905 rare nasal tumors, of which
      29,121 are olfactory epithelial neuroblastomas) is much greater than the number
      of these tumors actually observed per year (910 total nasal tumors, of which 66
      are olfactory neuroblastomas) over the period 1973-2006. This suggests that using
      rat nasal tumor data to derive a naphthalene URF for humans should be re
      evaluated.

PMID- 20156513
TI  - The integrity of corpus callosum and cluster B personality disorders: a
      quantitative MRI study in juvenile myoclonic epilepsy.
AB  - Evidence suggests increased prevalence of cluster B personality disorders (PD)
      among patients with juvenile myoclonic epilepsy (JME), which has been associated
      with worse seizure control and more psychosocial dysfunctions. A preliminary
      voxel-based morphometry study demonstrated corpus callosum (CC) volume reduction
      in patients with JME and cluster B PD, particularly in the posterior midbody and
      isthmus. In this study we aimed to follow up these results with region of
      interest analysis. Sixteen JME patients with cluster B PD, 38 JME patients
      without any psychiatric disorder, and 30 demographically matched healthy controls
      submitted to a psychiatric evaluation and a magnetic resonance imaging scan. The
      total and regional callosal areas were obtained from the midsagittal slice using
      a semi-automated program. Psychiatric evaluation was performed through SCID-I and
      -II. Significant reductions in the posterior region of the CC were observed in
      the JME with PD group relative to the other groups. These data support previous
      findings of callosal reductions in cluster B PD, as well as a possible
      involvement of CC in patients with JME and such personality characteristics.

PMID- 20156514
TI  - Proposed dose equivalence between clonazepam and pramipexole in patients with
      restless legs syndrome.
AB  - BACKGROUND: Dopamine agonists are accepted as the first-line medications for
      restless legs syndrome (RLS). In some Asian countries, clonazepam is one of the
      prevalent medications for RLS because of its effect on sleep disturbances. To
      date, there have not been any studies that examined equivalent doses of
      pramipexole and clonazepam. To evaluate equivalent doses of pramipexole and
      clonazepam in RLS, we investigated the efficacy and tolerability after conversion
      from clonazepam to pramipexole, and examined dose equivalence between the two
      prescriptions. METHODS: In a prospective, open-label, multicenter study, 26 RLS
      patients treated with clonazepam (mean age: 69.2+/-11.0years old) were enrolled
      and then rapidly switched to pramipexole using a conversion calculation of 4:1
      for daily doses. Then the daily dose of pramipexole was up titrated or tapered by
      0.125mg/day at each subsequent examination. RLS symptoms and daytime somnolence
      were evaluated using the International RLS Study Group rating scale (IRLS),
      Clinical Global Impressions - Severity of illness (CGI-S) and the Epworth
      Sleepiness Scale (ESS), respectively. RESULTS: Conversion from clonazepam to
      pramipexole resulted in significant reductions of IRLS (16.3+/-8.7 to 9.1+/-6.3)
      and ESS (6.5+/-4.2 to 4.4+/-3.2). CGI scores demonstrated improvement after
      conversion. In 4 patients (15%), adverse events such as somnolence, sensation of
      oppression in the lower limbs, diarrhea, or nausea were present. Correlation
      analysis demonstrated a significant relationship between these daily doses.
      Spearman's correlation coefficient was 0.662. Our study, however, has some
      limitations since it is an open-label trial and includes only 26 patients.
      Further studies using a double-blind design or a crossover design are
      recommended. CONCLUSIONS: Statistical analysis demonstrated a 4:1 conversion for
      clonazepam to pramipexole. When switchover from clonazepam to pramipexole is
      done, this conversion ratio may be helpful to determine the initial dose of
      pramipexole for treating RLS.

PMID- 20156515
TI  - The role of zinc in neurodegenerative inflammatory pathways in depression.
AB  - According to new hypothesis, depression is characterized by decreased
      neurogenesis and enhanced neurodegeneration which, in part, may be caused by
      inflammatory processes. There is much evidence indicating that depression, age
      related changes often associated with impaired brain function and cognitive
      performances or neurodegenerative processes could be related to dysfunctions
      affecting the zinc ion availability. Clinical studies revealed that depression is
      accompanied by serum hypozincemia, which can be normalized by successful
      antidepressant treatment. In patients with major depression, a low zinc serum
      level was correlated with an increase in the activation of markers of the immune
      system, suggesting that this effect may result in part from a depression-related
      alteration in the immune-inflammatory system. Moreover, a preliminary clinical
      study demonstrated the benefit of zinc supplementation in antidepressant therapy
      in both treatment non-resistant and resistant patients. In the preclinical study,
      the antidepressant activity of zinc was observed in the majority of rodent tests
      and models of depression and revealed a causative role for zinc deficiency in the
      induction of depressive-like symptoms, the reduction of neurogenesis and neuronal
      survival or impaired learning and memory ability. This paper provides an overview
      of the clinical and experimental evidence that implicates the role of zinc in the
      pathophysiology and therapy of depression within the context of the inflammatory
      and neurodegenerative hypothesis of this disease.

PMID- 20156516
TI  - Sex differences in the effects of N,N-diethyllysergamide (LSD) on behavioural
      activity and prepulse inhibition.
AB  - The aim of this study was to describe sex differences in the behavioural effects
      of N,N-diethyllysergamide (LSD) (locomotor activity and other behavioural
      repertoire in the open field) and its effects on sensorimotor gating in rats
      (prepulse inhibition (PPI) of the acoustic startle reaction). Three groups of
      animals were analysed: males, oestral and pro-oestral phase females (EP females),
      and metoestral and dioestral phase females (MD females). LSD (5, 50 and 200
      microg/kg subcutaneously) attenuated locomotor activity and normal behavioural
      repertoire, and induced flat body posture, wet dog shakes and disrupted PPI. The
      most prominent behavioural findings of LSD were for LSD 200 microg/kg which
      suppressed almost all behavioural activity. LSD had mainly inhibitory locomotor
      effects in males and MD females, yet in EP female rats LSD increased locomotion
      during the second half of testing period. The main sex differences were observed
      in locomotor and exploratory behaviour. Both EP and MD females were less
      sensitive to hypolocomotor effects of LSD and had less pronounced thigmotaxis
      than males. Further EP females had increased rearing after LSD 5microg/kg. On the
      contrary although LSD disrupted PPI in males and MD female rats, EP females were
      protected from this disruptive effect. Thus, EP females seem to have a lower
      sensitivity to LSD behavioural actions.

PMID- 20156517
TI  - Stability of major allergen tropomyosin and other food proteins of mud crab
      (Scylla serrata) by in vitro gastrointestinal digestion.
AB  - Stability in simulated gastric fluid is regarded as an important parameter for
      the estimation of food allergenicity. In this study, the digestive stability of
      allergenic protein tropomyosin (TM) and other food proteins from mud crab in
      simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) digestion
      assay system was investigated and compared by SDS-PAGE and Western blot. In SGF
      system, proteins such as actin and the original band of myosin heavy chain (MHC)
      were rapidly degraded within a short period of time, while TM was relatively
      resistant to pepsin digestion. In SIF system, MHC was easily decomposed, while TM
      and actin were similarly resistant to digestion. Further study by IgE
      immunoblotting and inhibition ELISA using sera from crab-allergic patients
      indicated that allergenicity of TM was partially decreased, suggesting proteinase
      digestion is effective in reducing the allergenicity of crab TM.

PMID- 20156518
TI  - Arsenic-induced myocardial injury: protective role of Corchorus olitorius leaves.
AB  - Groundwater arsenic contamination in Bangladesh and its adjoining part of West
      Bengal (India) is reported to be the biggest arsenic calamity in the world in
      terms of the affected population. Tossa jute, Corchorus olitorius is a popular
      crop of this arsenic prone population. The present study was undertaken to
      evaluate the protective effect of aqueous extract of C. olitorius leaves (AECO)
      against sodium arsenite (NaAsO(2)) induced cardiotoxicity in experimental rats.
      The animals exposed to NaAsO(2) (10mg/kg, p.o.) for 10days exhibited a
      significant inhibition (p<0.01) of superoxide dismutase, catalase, glutathione-S
      transferase, glutathione peroxidase, glutathione reductase and reduced
      glutathione level in myocardial tissues of rats. In addition, it significantly
      increased (p<0.01) oxidized glutathione, malondialdehyde and protein carbonyl
      content in myocardial tissue. Treatment with AECO (50 and 100mg/kg, p.o.) for
      15days prior to NaAsO(2)-intoxication significantly protected cardiac tissue
      against arsenic-induced oxidative impairment. In addition, AECO pretreatment
      significantly prevented NaAsO(2) induced hyperlipidemia, cardiac arsenic content
      and DNA fragmentation in experimental rats. Histological studies of myocardial
      tissue supported the protective activity of the AECO. The results concluded that
      the treatment with AECO prior to arsenic intoxication has significant protecting
      effect against arsenic-induced myocardial injury.

PMID- 20156519
TI  - Organochlorine pesticide residues in wheat from Konya region, Turkey.
AB  - The present study has been carried out to evaluate the organochlorine pesticide
      contamination in wheat from Konya region. This region is the largest area of
      cereal production in Turkey. The contamination level has been determined
      according to the European Community Directives. Different wheat samples (36) were
      obtained from local farmers and wheat factories in this region. All the wheat
      samples examined were found to be contaminated by organochlorine pesticide
      residues of cis-Chlordane and methoxychlor. Chlordane isomers, methoxychlor, DDT
      and its metabolites, aldrin, beta HCH, heptachlor and lindane have been found to
      be the highest organochlorine pesticide residues. In some of these samples,
      various organochlorine pesticide residues have been determined to be higher than
      European Community maximum residual limits. The residues of aldrin in one sample,
      trans-Chlordane in one sample, oxy-chlordane in eight samples and methoxychlor in
      one sample were found to be in excess of EC MRLs. Since most of the samples have
      been found to be contaminated with residues and some residues exceed EC MRLs, a
      control of organochlorine pesticide residues in wheat is necessary.

PMID- 20156520
TI  - Artemisia fukudo essential oil attenuates LPS-induced inflammation by suppressing
      NF-kappaB and MAPK activation in RAW 264.7 macrophages.
AB  - In the present study, the chemical constituents of Artemisia fukudo essential oil
      (AFE) were investigated using GC-MS. The major constituents were alpha-thujone
      (48.28%), beta-thujone (12.69%), camphor (6.95%) and caryophyllene (6.01%). We
      also examined the effects of AFE on the production of nitric oxide (NO),
      prostaglandin E(2) (PGE(2)), tumour necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, and IL-6, in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages.
      Western blotting and RT-PCR tests indicated that AFE has potent dose-dependent
      inhibitory effects on pro-inflammatory cytokines and mediators. We investigated
      the mechanism by which AFE inhibits NO and PGE(2) by examining the level of
      nuclear factor-kappaB (NF-kappaB) activation within the mitogen-activated protein
      kinase (MAPK) pathway, which is an inflammation-induced signal pathway in RAW
      264.7 cells. AFE inhibited LPS-induced ERK, JNK, and p38 phosphorylation.
      Furthermore, AFE inhibited the LPS-induced phosphorylation and degradation of
      Ikappa-B-alpha, which is required for the nuclear translocations of the p50 and
      p65 NF-kappaB subunits in RAW 264.7 cells. Our results suggest that AFE might
      exert an anti-inflammatory effect by inhibiting the expression of pro
      inflammatory cytokines. Such an effect is mediated by a blocking of NF-kappaB
      activation which consequently inhibits the generation of inflammatory mediators
      in RAW264.7 cells. AFE may be useful for treating inflammatory diseases.

PMID- 20156521
TI  - Gene-environmental interactions and organophosphate toxicity.
AB  - Organophosphates (OPs) are an important class of insecticides that in the UK have
      been widely used for treating sheep for ectoparasites as well as in other sectors
      of the farming industry. Health problems associated with acute OP toxicity are
      well defined but, ill-health induced by chronic exposures to OPs remains
      controversial. A substantial number of sheep farmers complain of chronic ill
      health which they attribute to repeated exposure to OPs. If OPs were associated
      with chronic ill-health then individuals with specific defects in OP metabolism
      might be expected to be at greater risk of ill-health following exposure. To
      examine such a hypothesis, the characterisation of both OP exposure and those
      pathways which lead to the formation and removal of the active OP metabolites
      becomes important. A wide range of OPs have previously been used to treat sheep
      but currently the only OP licenced for treating sheep is diazinon. Immediately
      after treatment, farmers' urines contain detectable levels of OP metabolites but
      few farmers have a significant decrease in plasma cholinesterase activity.
      Diazinon, like chlorpyrifos, is an organothiophosphate which is metabolised,
      particularly by cytochrome p450s, to the corresponding active oxon form. CYP
      metabolism also leads to the inactivation of the parent compound and the relative
      balance of inactivation and activation can depend upon the specific OP and the
      CYP isoform. OP oxons are inactivated by serum paraoxonase (PON1) and mice
      lacking PON1 activity are susceptible to oxon and parent OP induced toxicity.
      PON1 polymorphisms at positions 192 (R form with arginine at 192 and Q with
      glutamine) and 55 (L form with a leucine and a M form with methionine) influence
      paroxonase activity. The effect of the Q192R polymorphism is substrate specific
      with reports indicating that diazoxon is metabolised less by the R isoform. In a
      study of sheep farmers within the UK, the R allele was associated with an
      increased risk of self-reported chronic ill-health, a result consistent with the
      hypothesis that this ill-health may have been caused by OPs. Studies in other
      populations exposed to pesticides also show associations between ill-health and
      PON1 Q192R polymorphisms but not consistently so. This is not surprisingly given
      that exposure is often poorly characterised. In vivo models also suggest that
      PON1 genotypes may have little influence on susceptibility at low doses of the
      parent OP. Hence further work is required not only to better characterise OP
      exposure in humans populations but also to identify those populations susceptible
      to OP toxicity.

PMID- 20156522
TI  - Sphingosine kinase: Role in regulation of bioactive sphingolipid mediators in
      inflammation.
AB  - Sphingolipids and their synthetic enzymes are emerging as important mediators in
      inflammatory responses and as regulators of immune cell functions. In particular,
      sphingosine kinase (SK) and its product sphingosine-1-phosphate (S1P) have been
      extensively implicated in these processes. SK catalyzes the phosphorylation of
      sphingosine to S1P and exists as two isoforms, SK1 and SK2. SK1 has been shown to
      be activated by cytokines including tumor necrosis factor-alpha (TNF-alpha) and
      interleukin1-beta (IL1-beta). The activation of SK1 in this pathway has been
      shown to be, at least in part, required for mediating TNF-alpha and IL1-beta
      inflammatory responses in cells, including induction of cyclo-oxygenase 2 (COX2).
      In addition to their role in inflammatory signaling, SK and S1P have also been
      implicated in various immune cell functions including, mast cell degranulation,
      migration of neutrophils, and migration and maturation of lymphocytes. The
      involvement of sphingolipids and sphingolipid metabolizing enzymes in
      inflammatory signaling and immune cell functions has implicated these mediators
      in numerous inflammatory disease states as well. The contribution of these
      mediators, specifically SK1 and S1P, to inflammation and disease are discussed in
      this review.

PMID- 20156524
TI  - Preliminary findings in ablating the nucleus accumbens using stereotactic surgery
      for alleviating psychological dependence on alcohol.
AB  - We studied the effect of stereotactic surgery in cases of alcohol dependence.
      Twelve patients with a psychological dependence on alcohol (treated
      systematically with medication for detoxification 3-8 times in various
      rehabilitation centers before, but had relapsed within 2 weeks after withdrawal)
      were treated by ablating the nucleus accumbens (NA(C)) bilaterally using
      stereotactic surgery. The therapeutic effect and safety evaluation index of the
      surgery were analyzed. The timing of the conducted evaluations was preoperatively
      and in the sixth postoperative month. Currently, relapse has not occurred in 9
      cases. Relapse occurred in 3 cases after surgery. The prevalence of relapse was
      16.7% within 6 months, and 25% within 12 months. Non-specific complications of
      this type of surgery (e.g., intracranial hematoma, infection) were not observed.
      One case in 12 patients suffered dysosmia, but he recovered completely 4 months
      later after surgery. The full-scale intelligence quotient (FSIQ) and memory
      quotient (MQ) of these patients were significantly improved 6 months
      postoperatively compared with preoperatively. The severity of alcohol dependence
      scale and a scale measuring alcohol craving in these patients were significantly
      decreased. There were also significant changes over time in the Minnesota
      multiphasic personality inventory (MMPI) profile, suggesting a decrease in
      depression, irritability, and psychopathy. Ablating specified targets (NA(C))
      using stereotactic surgery is a safe method to alleviate alcohol craving, reduce
      relapse rates and improve quality-of-life in patients with psychological
      dependence on alcohol.

PMID- 20156523
TI  - Vitamin D and the intracrinology of innate immunity.
AB  - An immunomodulatory role for vitamin D was first proposed more than 25 years ago,
      based on two salient observations. Firstly it was shown that
      monocytes/macrophages from patients with the granulomatous disease sarcoidosis
      constitutively synthesize the active form of vitamin D, 1,25-dihydroxyvitamin D
      (1,25(OH)(2)D) from precursor 25-hydroxyvitamin D (25OHD). Secondly, the receptor
      for 1,25(OH)(2)D (vitamin D receptor, VDR) is detectable in activated,
      proliferating lymphocytes. These observations suggested a mechanism whereby
      1,25(OH)(2)D produced by monocytes could act upon adjacent T-cells or B-cells,
      but the impact of such a system on normal immune regulation was uncertain.
      Indeed, it is only in recent years that a much clearer picture of the role of
      vitamin D as a determinant of immune responsiveness has emerged. Two new concepts
      have prompted this change. Firstly studies of innate immunity have shown that
      intracrine induction of antimicrobial activity by vitamin D is a pivotal
      component of monocyte/macrophage response to infection. Secondly, it is now clear
      that sub-optimal vitamin D status is a common feature of many populations
      throughout the world, with the potential to compromise monocyte/macrophage
      metabolism of 25OHD and subsequent actions of 1,25(OH)(2)D. The current review
      details these new developments with specific reference to the metabolic and
      signaling mechanisms associated with innate immune regulation by vitamin D and
      implications for human disease.

PMID- 20156525
TI  - Reactive oxygen species levels and DNA fragmentation on astrocytes in primary
      culture after acute exposure to low intensity microwave electromagnetic field.
AB  - The exposure of primary rat neocortical astroglial cell cultures to acute
      electromagnetic fields (EMF) in the microwave range was studied. Differentiated
      astroglial cell cultures at 14 days in vitro were exposed for 5, 10, or 20min to
      either 900MHz continuous waves or 900MHz waves modulated in amplitude at 50Hz
      using a sinusoidal waveform and 100% modulation index. The strength of the
      electric field (rms value) at the sample position was 10V/m. No change in
      cellular viability evaluated by MTT test and lactate dehydrogenase release was
      observed. A significant increase in ROS levels and DNA fragmentation was found
      only after exposure of the astrocytes to modulated EMF for 20min. No evident
      effects were detected when shorter time intervals or continuous waves were used.
      The irradiation conditions allowed the exclusion of any possible thermal effect.
      Our data demonstrate, for the first time, that even acute exposure to low
      intensity EMF induces ROS production and DNA fragmentation in astrocytes in
      primary cultures, which also represent the principal target of modulated EMF. Our
      findings also suggest the hypothesis that the effects could be due to
      hyperstimulation of the glutamate receptors, which play a crucial role in acute
      and chronic brain damage. Furthermore, the results show the importance of the
      amplitude modulation in the interaction between EMF and neocortical astrocytes.

PMID- 20156526
TI  - Prosurvival effect of human wild-type alpha-synuclein on MPTP-induced toxicity to
      central but not peripheral catecholaminergic neurons isolated from transgenic
      mice.
AB  - In the present work we report the generation of a new line of alpha-synuclein
      (alpha-SYN) transgenic mice in which the human wild-type alpha-SYN cDNA is
      expressed under the control of a tyrosine hydroxylase (TH) promoter. We provide
      evidence that the ectopic protein is found in TH expressing neurons of both
      central and peripheral nervous systems. The transgene is expressed very early in
      development coinciding with the activity of the TH promoter and in the adult
      brain the human protein distributes normally to the nerve endings and cell bodies
      of dopaminergic nigral neurons without any evidence of abnormal aggregation. Our
      results indicate that expression of human wild-type alpha-SYN does not affect
      normal development or maintenance of TH immunoreactive nigral neurons, striatal
      dopamine content, or locomotor activity. Systemic administration of the
      parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induces a loss of TH immunoreactive nigral neurons and terminals and of dopamine
      levels to the same degree in both transgenic and non-transgenic adult mice.
      Intoxication also results in a similar loss of cardiac noradrenaline in both
      genotypes. Surprisingly, cultured transgenic ventral mesencephalic fetal
      dopaminergic neurons exhibit complete resistance to cell death induced by 1
      methyl-4-phenylpyridinium ion (MPP(+)) intoxication, without changes in dopamine
      transporter (DAT) surface levels. Interestingly, this protection is not observed
      in other populations of catecholaminergic neurons such as peripheral sympathetic
      neurons, despite their high sensitivity to MPP(+)in vitro.

PMID- 20156527
TI  - Morphine preconditioning reduces lipopolysaccharide and interferon-gamma-induced
      mouse microglial cell injury via delta 1 opioid receptor activation.
AB  - Microglial cells play an important role in the inflammatory response of a broad
      range of brain diseases including stroke, brain infection and neurodegenerative
      diseases. However, there is very little information regarding how to protect
      microglial cells. Here, we showed that incubation of the C8-B4 mouse microglial
      cells with lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma) induced
      cytotoxicity as assessed by the amount of lactate dehydrogenase (LDH) released
      from the cells. Preconditioning the cells with morphine for 30 min concentration
      dependently reduced LPS plus IFN gamma-induced cell injury. This morphine
      preconditioning effect was abolished by naloxone, a general opioid receptor
      antagonist, by naltrindole, a selective delta opioid receptor antagonist and by 7
      benzylidenenaltrexone maleate, a selective delta(1) opioid receptor antagonist.
      However, this protective effect was not affected by beta-funaltrexamine, a
      selective mu opioid receptor antagonist, nor-binaltorphimine, a selective kappa
      opioid receptor antagonist or naltriben, a selective delta(2) opioid receptor
      antagonist. LPS plus IFN gamma induced the expression of inducible nitric oxide
      synthase (iNOS), which was not affected by morphine preconditioning. Our results
      suggest that morphine induced a preconditioning effect in microglial cells. This
      effect may be mediated by delta 1 opioid receptors and may not be through
      inhibiting the expression of iNOS, a potentially harmful protein.

PMID- 20156528
TI  - The medial preoptic area is necessary for motivated choice of pup- over cocaine
      associated environments by early postpartum rats.
AB  - Converging evidence suggests that the motivation to seek cocaine during the
      postpartum period is significantly impacted by the competing incentives of
      offspring, a stimulus unique to this life stage. In the present study, the
      functional role of the medial preoptic area (mPOA), a critical site involved in
      maternal responsiveness, on processing incentive value of pup-associated cues and
      influencing response allocation for pup- over cocaine-associated environments was
      investigated using a concurrent pup/cocaine choice conditioned place preference
      (CPP) paradigm. Early postpartum females with bilateral guide cannulae aimed into
      the mPOA or into anatomical control sites were conditioned, from postpartum days
      (PPD) 4 to 7, to associate different uniquely featured environments with pups or
      cocaine. CPP was tested on PPD8 following intra-mPOA infusions of either 2%
      bupivacaine or saline vehicle. In two additional experiments, the effects of
      intra-mPOA infusions of bupivacaine on expression of conditioned responding
      induced by environments associated with either pups or cocaine were examined
      separately. Transient inactivation of the mPOA selectively blocked the
      conditioned preferences for pup-associated environments, significantly
      contrasting the robust pup-CPP found in non-surgical and intra-mPOA vehicle
      treated females. In contrast, mPOA inactivation failed to alter cocaine-CPP in
      postpartum females. When given a choice between environments associated with pups
      or cocaine, transient functional inactivation of the mPOA altered choice
      behavior, biasing the preference of females toward cocaine-associated
      environments, such that almost all preferred cocaine- and none the pup-associated
      option. The anatomical specificity was revealed when inactivation of adjacent
      regions to the mPOA did not affect CPP responses for pups. The findings support a
      critical role for the mPOA in mediating pup-seeking behavior, and further suggest
      that the competing properties of pups over alternative incentives, including
      drugs of abuse, rely on mPOA integrity to provide relevant pup-related
      information to the circuitry underlying the choice behavior between pups and
      alternative stimuli.

PMID- 20156530
TI  - Herbal drugs: standards and regulation.
AB  - The use of herbal drugs for the prevention and treatment of various health
      ailments has been in practice from time immemorial. Generally it is believed that
      the risk associated with herbal drugs is very less, but reports on serious
      reactions are indicating to the need for development of effective marker systems
      for isolation and identification of the individual components. Standards for
      herbal drugs are being developed worldwide but as yet there is no common
      consensus as to how these should be adopted. Standardization, stability and
      quality control for herbal drugs are feasible, but difficult to accomplish.
      Further, the regulation of these drugs is not uniform across countries. There are
      variations in the methods used across medicine systems and countries in achieving
      stability and quality control. The present study attempts to identify the
      evolution of technical standards in manufacturing and the regulatory guideline
      development for commercialization of herbal drugs.

PMID- 20156529
TI  - Localization of dopamine- and cAMP-regulated phosphoprotein-32 and inhibitor-1 in
      area 9 of Macaca mulatta prefrontal cortex.
AB  - The actions of dopamine D1 family receptors (D1R) depend upon a signal
      transduction cascade that modulates the phosphorylation state of important
      effector proteins, such as glutamate receptors and ion channels. This is
      accomplished both through activation of protein kinase A (PKA) and the inhibition
      of protein phosphatase-1 (PP1). Inhibition of PP1 occurs through PKA-mediated
      phosphorylation of dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP-32)
      or the related protein inhibitor-1 (I-1), and the availability of DARPP-32 is
      essential to the functional outcome of D1R activation in the basal ganglia. While
      D1R activation is critical for prefrontal cortex (PFC) function, especially
      working memory, the functional role played by DARPP-32 or I-1 is less clear. In
      order to examine this more thoroughly, we have utilized immunoelectron microscopy
      to quantitatively determine the localization of DARPP-32 and I-1 in the neuropil
      of the rhesus monkey PFC. Both were distributed widely in the different
      components of the neuropil, but were enriched in dendritic shafts. I-1 label was
      more frequently identified in axon terminals than was DARPP-32, and DARPP-32
      label was more frequently identified in glia than was I-1. We also quantified the
      extent to which these proteins were found in dendritic spines. DARPP-32 and I-1
      were present in small subpopulations of dendritic spines, (4.4% and 7.7% and
      respectively), which were substantially smaller than observed for D1R in our
      previous studies (20%). Double-label experiments did not find evidence for
      colocalization of D1R and DARPP-32 or I-1 in spines or terminals. Thus, at the
      least, not all prefrontal spines which contain D1R also contain I-1 or DARPP-32,
      suggesting important differences in D1R signaling in the PFC compared to the
      striatum.

PMID- 20156531
TI  - Two-step maturation of immature DCs with proinflammatory cytokine cocktail and
      poly(I:C) enhances migratory and T cell stimulatory capacity.
AB  - Effective induction of cell-mediated immune responses strongly depends on the
      ability of dendritic cells (DCs) to produce Th1-polarizing cytokines, migrate to
      lymph nodes and stimulate T cells through antigen-presenting complex and
      costimulatory molecules. While various protocols for optimizing DC maturation
      with single or multiple stimuli mimicking infections or inflammatory milieu have
      been proposed for the generation of DCs with features desired for clinical
      application, stepwise maturation of DCs by these multiple stimuli has not been
      systemically assessed. Among the combinations of several immune-modulating
      factors with known effects on DC maturation, we found that stepwise DC maturation
      with cytokine cocktail (TNF-alpha+IL-6+IL-1 beta+PGE(2)) followed by poly(I:C)
      stimulation enhanced the production of IL-12 with strong allostimulatory
      capacity. While there were no significant differences between DC matured by
      simultaneous or sequential activation by cytokine cocktail and poly(I:C) in
      expression of markers and costimulatory molecules of mature DCs, the delivery of
      inflammatory signal prior to poly(I:C) results in sustained interleukin-12
      expression with reduced IL-10 than DC matured by simultaneous stimulation. This
      sequential stimulation significantly increased migratory capacity in response to
      CCL21 and CXCL12 compared to DC matured with cytokine cocktail. Furthermore,
      these DCs retained their responsiveness to CD40L stimulation in secondary IL-12
      production and efficiently generated autologous antigen-specific effector T cells
      as evidenced by ELISPOT assay. Thus, we propose a novel DC maturation protocol in
      which stimulation of DCs with cytokine cocktail and subsequently with poly(I:C)
      generates DCs with a high migratory capacity with a preferential Th1 inducing
      capacity.

PMID- 20156532
TI  - The R2R3 Myb protein family in Entamoeba histolytica.
AB  - The MYB DNA-binding domain is conserved in vertebrates, plants, and fungi. This
      domain mediates the DNA-binding activity of proteins (that have transcription
      factor activity) in a sequence-specific manner and is also used for the
      protection of telomeric regions. The MYB DNA-binding domain contains three
      imperfect conserved repeats of 52 amino acids (R1, R2, and R3). Within each
      repeat, there are three tryptophans that are separated by 18 or 19 amino acids.
      In order to understand the role of Myb transcription factors in Entamoeba
      histolytica, we searched for MYB DNA-binding domain containing proteins using the
      amino acid sequence of human c-Myb as the query. We found 34 putative MYB DNA
      binding domain containing proteins, which clustered into three monophyletic
      groups. Family I members conserve only the R2 and R3 repeats in their MYB DNA
      binding domain and were dubbed in this report as EhMybR2R3. Family II includes
      single-repeat proteins related to human telomeric binding proteins. Family III is
      predicted to comprise proteins with one single repeat where the region
      corresponding to the conserved tryptophan of the third alpha helix is replaced by
      a (S)/(T)HAQK(Y)/(F)F motif; this family was named EhMybSHAQKYF. In this work, we
      focused on proteins that belong to the EhMybR2R3 family. RT-PCR analysis showed
      that EhMybR2R3 genes were differentially expressed in trophozoites grown in basal
      culture conditions. Purified rEhMyb10 protein, belonging to the EhMybR2R3 family,
      was able to bind a consensus Myb recognition element in vitro. In addition, using
      nuclear extracts from trophozoites of E. histolytica, we were able to detect Myb
      DNA-binding activity to this sequence. Our in silico surveys demonstrated that
      this consensus sequence is present in E. histolytica gene promoters.
      Interestingly, these promoters include different families of genes that are
      related to signal transduction, vesicular transport, heat shock response, and
      virulence. Thus, Myb putative transcription factors in E. histolytica could be
      involved in the transcriptional regulation of genes participating in several
      different pathways.

PMID- 20156533
TI  - Generation of T cell responses targeting the reactive metabolite of halothane in
      mice.
AB  - Immune-mediated adverse drug reactions (IADRs) represent a significant problem in
      clinical practice and drug development. Studies of the underlying mechanisms of
      IADRs have been hampered by the lack of animal models. Halothane causes severe
      allergic hepatitis with clinical features consistent with an IADR. Our ultimate
      goal is to develop a mouse model of halothane hepatitis. Evidence suggests that
      adaptive immune responses targeting liver protein adducts of the reactive
      metabolite (trifluoroacetyl (TFA)) play an important role in the pathogenesis.
      The present study demonstrated that the combination of an anti-CD40 antibody (Ab)
      and a Toll-like receptor (TLR) agonist served as a potent adjuvant in generating
      TFA-specific T cell responses in mice. Both CD4(+) and CD8(+) subsets of T cells
      were activated and the TFA-specific responses were detected not only in the
      spleen but also in the liver of mice immunized with mouse serum albumin adducts
      of TFA (TFA-MSA) plus the combined CD40/TLR agonist. Whereas all three TLR
      agonists examined were effective in eliciting TFA-specific immune responses in
      BALB/cByJ mice, only polyI:C was effective in DBA/1 mice and none of the TLR
      agonists could aid the generation of TFA-specific T cells in C57BL/6J mice. This
      result, combined with our previous finding that BALB/cByJ mice were the most
      susceptible to halothane-induced acute liver injury, provides the basis for
      employing this strain in future studies. Collectively, our data demonstrated the
      successful completion of a crucial first step in the development of a murine
      model of halothane hepatitis.

PMID- 20156534
TI  - Comparative study of oxime-induced reactivation of erythrocyte and muscle AChE
      from different animal species following inhibition by sarin or paraoxon.
AB  - Standard treatment of acute poisoning by organophosphorus compounds (OP) includes
      administration of an antimuscarinic (e.g. atropine) and of an oxime-based
      reactivator of OP-inhibited acetylcholinesterase (AChE). A recently introduced
      dynamically working in vitro model with real-time determination of membrane-bound
      AChE activity was shown to be a very versatile and promising model to investigate
      oxime-induced reactivation kinetics of OP-inhibited enzyme. In this assay, human
      AChE from erythrocytes or muscle tissue was immobilized on a particle filter.
      This bioreactor was continuously perfused with substrate and chromogen and AChE
      activity was analyzed on-line in a flow-through detector. The model has been
      successfully adopted to Rhesus monkey, swine and guinea pig erythrocytes and
      intercostal muscle AChE. In addition, the basic kinetic constants of inhibition,
      aging, spontaneous- and oxime-induced-reactivation of erythrocyte AChE from these
      species were determined with a standard static model. The major findings were, in
      part substantial species differences in the inhibition (sarin, paraoxon) and
      reactivation kinetics (obidoxime, HI 6) of erythrocyte AChE, but comparable
      kinetics of inhibition and reactivation between erythrocyte and muscle AChE.
      Hence, these data provide further support of the assumption that erythrocyte AChE
      is an adequate surrogate of muscle (synaptic) AChE and admonish that major
      species differences have to be considered for the design and evaluation of
      therapeutic animal models.

PMID- 20156535
TI  - Light induced fluorescence for predicting API content in tablets: sampling and
      error.
AB  - The use of a light induced fluorescence (LIF) instrument to estimate the total
      content of fluorescent active pharmaceutical ingredient in a tablet from surface
      sampling was demonstrated. Different LIF sampling strategies were compared to a
      total tablet ultraviolet (UV) absorbance test for each tablet. Testing was
      completed on tablets with triamterene as the active ingredient and on tablets
      with caffeine as the active ingredient, each with a range of concentrations. The
      LIF instrument accurately estimated the active ingredient within 10% of total
      tablet test greater than 95% of the time. The largest error amongst all of the
      tablets tested was 13%. The RMSEP between the techniques was in the range of 4.4
      7.9%. Theory of the error associated with the surface sampling was developed and
      found to accurately predict the experimental error. This theory uses one
      empirically determined parameter: the deviation of estimations at different
      locations on the tablet surface. As this empirical parameter can be found
      rapidly, correct use of this prediction of error may reduce the effort required
      for calibration and validation studies of non-destructive surface measurement
      techniques, and thereby rapidly determine appropriate analytical techniques for
      estimating content uniformity in tablets.

PMID- 20156536
TI  - Surface modification of lactose inhalation blends by moisture.
AB  - We present an investigation of the effects of relative humidity (RH) on lactose
      powders during storage, with the aims of determining the humidity conditions
      under which lactose inhalation blends are stable, and characterising the surface
      changes that occur as a result of water condensation. Lactose inhalation powders
      manufactured by milling and sieving were stored in environments of RH from 32% to
      100% (at room temperature) and changes in surface properties were observed using
      BET nitrogen adsorption, environmental scanning electron microscopy and laser
      diffraction particle size analysis. We found that the specific surface area of
      all lactose powders decreased during storage, with the rate of decrease and final
      drop being larger at higher RH (ranging from a 62% decrease at 100% RH to a 34%
      decrease at 32% RH, at room temperature). The specific surface area decrease
      corresponded to a reduction in the volume of fine particles (<5 microm) in the
      blend. Two effects were found to contribute to the decrease in specific surface
      area: the smoothing of coarse particles, attributed to the surface fine particles
      undergoing deliquescence due to their enhanced solubility by the Kelvin effect
      (i.e. due to their greater curvature and consequently greater surface energy),
      and solid bridging between fine particles in agglomerates, such that loose fine
      particles disappeared from the powder blend, having bonded with coarser
      particles. These changes in particle properties resulting from moisture exposure
      are expected to influence the fine particle fraction of drug released from the
      powder blends, and the observation that lactose inhalation blends were unstable
      even at 32% RH could potentially be a concern for the pharmaceutical industry.

PMID- 20156537
TI  - Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of
      aromatase inhibitor 7alpha-APTADD to breast cancer cells.
AB  - Transferrin (Tf)-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA)
      nanoparticles carrying the aromatase inhibitor, 7alpha-(4'-amino)phenylthio-1,4
      androstadiene-3,17-dione (7alpha-APTADD), were synthesized by a solvent injection
      method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug
      to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were
      optimized to obtain nanoparticles with desired sizes and drug loading efficiency.
      The optimal formulation had a drug loading efficiency of 36.3+/-3.4%, mean
      diameter of 170.3+/-7.6nm and zeta potential of -18.9+/-1.5mV. The aromatase
      inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer
      cells. IC(50) value of the Tf-nanoparticles was ranging from 0.77 to 1.21nM, and
      IC(50) value of the nanoparticles was ranging from 1.90 to 3.41nM (n=3). The
      former is significantly lower than the latter (p<0.05). These results suggested
      that the aromatase inhibition activity of the Tf-nanoparticles was enhanced
      relative to that of the non-targeted nanoparticles, which was attributable to Tf
      receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA
      nanoparticles are potential vehicles for improving the efficiency and specificity
      of therapeutic delivery of aromatase inhibitors.

PMID- 20156538
TI  - The effect of particle size on the dehydration/rehydration behaviour of lactose.
AB  - Ethanolic suspensions of spray dried and micronized alpha lactose monohydrate
      (L(alpha)xH(2)O) with average particle size between 3 and 200 microm, have been
      prepared and their dehydration behaviour was investigated by (13)C CP-MASNMR
      spectroscopy. Sub-micron lactose suspension prepared by a novel high pressure
      homogenisation method has been compared with the standard ethanolic suspensions
      of (L(alpha).H(2)O prepared by reflux or static room temperature methods. In all
      cases, suspensions were shown to contain the stable anhydrous form of lactose
      ((L(alpha)(S)). Several approaches were employed to remove ethanol from these
      suspensions and the resulting dry lactose powders were then analysed by FT-IR,
      PXRD and SEM to evaluate the effect of drying procedure on type and distribution
      of lactose polymorphs and particle size. For samples with mean particle size
      greater than 1 microm, the stable anhydrous polymorphic form of lactose was
      retained on removal of the ethanol, although differences in the morphology and
      particle size of the crystals were apparent depending on method of suspension
      formation. Sub-micron (L(alpha)(S), while stable in dry conditions, has been
      shown to be less stable to atmospheric water vapour than (L(alpha)(S) with
      particle size between 3 and 200 microm.

PMID- 20156539
TI  - Nitric oxide photorelease from hydrogels and from skin containing a nitro
      ruthenium complex.
AB  - Nitric oxide (NO) is a gaseous molecule that has specific functions dictated by
      its localization and its kinetics of release. As NO-donors have a range of
      potential uses in the skin, much attention has been paid to the development of
      topical NO delivery systems. The aim of this work was to study the release rate
      and the skin penetration of the NO-donor cis-[Ru(NO(2))(bpy)(2)(4-pic)](+) from
      different gel formulations and their potential as topical NO delivery systems
      under light stimuli. Among the formulations developed, the anionic gel retarded
      the nitro-ruthenium complex diffusion and also obstructed NO release after light
      irradiation. On the other hand, NO release before light irradiation was observed
      when the complex was dispersed in the cationic chitosan gel, possibly due to oxi
      redox reactions between the amino groups of the polymer and the drug molecule.
      Finally, the non-ionic gel released the NO after light irradiation to the same
      extent as a drug aqueous solution at the same pH. The drug dispersed in this gel
      also penetrated into the stratum corneum skin layer, and the nitro-ruthenium
      complex present in the skin was able to release the NO after light stimuli,
      suggesting the potential use of this formulation as a topical NO delivery system.

PMID- 20156540
TI  - Evaluation of the transdermal permeation of different paraben combinations
      through a pig ear skin model.
AB  - Although parabens have several features of ideal preservatives, different studies
      have shown that they may affect human health due to their estrogenic activity.
      Therefore, various strategies have been applied to reduce their skin penetration.
      However, the effect of paraben combinations on transdermal permeation has not yet
      been investigated. Thus, the objective of this study was to evaluate paraben
      permeation in pig ear skin using a Franz diffusion cell system with capillary
      electrophoresis detection, in order to identify which paraben combinations
      (defined by a factorial design) have the lowest skin permeation. The permeation
      of isolated parabens was also evaluated and the permeation characteristics,
      obtained by the Moser model, confirmed that lipophilicity and molecular weight
      may influence the systemic absorption of these compounds. In previous tests using
      isolated parabens, methyl and ethyl parabens presented greater retention in the
      epidermis compared to the dermis, while propyl and butyl parabens had similar
      retention profiles in these layers. An increase in ethanol concentration and
      experimental time promoted greater parabens retention in the dermis compared to
      the epidermis. The binary combinations of methyl and ethyl parabens as well as of
      methyl and propyl parabens (added to several cosmetic products in order to
      increase the antimicrobial spectrum) reduced significantly their permeation rates
      through pig ear skin (with the exception of EP), probably due to the high
      retention of these parabens in the epidermis and dermis.

PMID- 20156541
TI  - Biophysical characterization of a liposomal formulation of cytarabine and
      daunorubicin.
AB  - The biophysical characterization of CPX-351, a liposomal formulation of
      cytarabine and daunorubicin encapsulated in a synergistic 5:1 molar ratio
      (respectively), is presented. CPX-351 is a promising drug candidate currently in
      two concurrent Phase 2 trials for treatment of acute myeloid leukemia. Its
      therapeutic activity is dependent on maintenance of the synergistic 5:1 drug:drug
      ratio in vivo. CPX-351 liposomes have a mean diameter of 107 nm, a single phase
      transition temperature of 55.3 degrees C, entrapped volume of 1.5 microL/micromol
      lipid and a zeta potential of -33 mV. Characterization of these physicochemical
      properties led to identification of an internal structure within the liposomes,
      later shown to be produced during the cytarabine loading procedure. Fluorescence
      labeling studies are presented that definitively show that the structure is
      composed of lipid and represents a second lamella. Extensive spectroscopic
      studies of the drug-excipient interactions within the liposome and in solution
      reveal that interactions of both cytarabine and daunorubicin with the copper(II)
      gluconate/triethanolamine-based buffer system play a role in maintenance of the
      5:1 cytarabine:daunorubicin ratio within the formulation. These studies
      demonstrate the importance of extensive biophysical study of liposomal drug
      products to elucidate the key physicochemical properties that may impact their in
      vivo performance.

PMID- 20156542
TI  - Physical instability, aggregation and conformational changes of recombinant human
      bone morphogenetic protein-2 (rhBMP-2).
AB  - The influence of two different pH values on the physical stability of recombinant
      human bone morphogenetic protein-2 (rhBMP-2) in aqueous solution was evaluated in
      the present work. RhBMP-2 in solution at pH 4.5 or 6.5 was characterized by
      intrinsic and extrinsic (Nile Red and 1,8-ANS) fluorescence spectroscopy, 90
      degrees light-scattering and transmission electron microscopy (TEM). Compared to
      the pH 4.5 solution, rhBMP-2 at pH 6.5 had (i) a stronger intrinsic fluorescence
      intensity, (ii) a longer fluorescence lifetime, (iii) a stronger 90 degrees light
      scattering intensity, (iv) a stronger Nile Red fluorescence intensity, (v) a
      higher Nile Red fluorescence anisotropy, (vi) a lower 1,8-ANS fluorescence
      intensity, (vii) a higher 1,8-ANS fluorescence anisotropy and (viii) a longer 1,8
      ANS fluorescence lifetime. Electron microscopy showed that rhBMP-2 at pH 4.5
      contained aggregates of about 100 nm in diameter. More and larger protein
      aggregates (0.1-2 microm) were observed in solution at pH 6.5. Taken together,
      these results indicate conformational changes and increased aggregation of rhBMP
      2 at pH 6.5 compared to pH 4.5, demonstrating a strong influence of pH on rhBMP-2
      physical stability. These observations must be considered when developing a
      delivery system for rhBMP-2.

PMID- 20156543
TI  - Evaluation of implantable actuators by means of a middle ear simulation model.
AB  - The extension of indication of implantable hearing aids to cases of conductive
      hearing loss pushed the development of these devices. There is now a great
      variety of devices available with different actuator concepts and different
      attachment points to the middle ear or inner ear fluid. But there is little
      comparative data available about the devices to provide an insight into
      advantages and disadvantages of different types of actuators and attachment
      points at the ossicular chain. This paper investigates two principle (idealized)
      types of actuators in respect of attachments points at the ossicular chain and
      direction of excitation. Other parts of implantable hearing aids like microphone,
      amplifier and signal processing electronics were not incorporated into this
      study. Investigations were performed by means of a mathematical simulation model
      of the middle ear (finite element model). Actuator performance and theoretical
      gain were calculated by harmonic analysis in the frequency range of 100-6000 Hz
      and were compared for the different situations. The stapes head proofed to be an
      ideal attachment point for actuators of both types as this position is very
      insensitive to changes in the direction of excitation. The implantable actuators
      showed higher ratio of equivalent sound pressure to radiated sound pressure
      compared to an open hearing aid transducer and should therefore allow for more
      functional gain.

PMID- 20156544
TI  - Treadmill exercise prevents aging-induced failure of memory through an increase
      in neurogenesis and suppression of apoptosis in rat hippocampus.
AB  - Aging leads to functional changes in the hippocampus, and consequently induces
      cognitive deficits, such as failure of memory. Neurogenesis in the hippocampal
      dentate gyrus continues throughout life, but steadily declines from early
      adulthood. Apoptosis occurs under various pathologic and physiologic conditions,
      and excessive apoptotic cell death can cause a number of functional disorders in
      humans. Apoptosis in the hippocampus also disturbs cognitive functions. In this
      study, we examined the effect of treadmill exercise on memory in relation to
      neurogensis and apoptosis in the hippocampal dentate gyrus of old-aged rats. The
      present results showed that loss of memory by aging was associated with a
      decrease in neurogenesis and an increase in apoptosis in the hippocampal dentate
      gyrus. Treadmill exercise improved short-term and spatial memories by enhancing
      neurogenesis and suppressing apoptosis in the hippocampal dentate gyrus of old
      aged rats. In the present study, we showed that treadmill exercise is a very
      useful strategy for preventing failure of memory in the elderly.

PMID- 20156546
TI  - Microemulsion-based organogels as matrices for lipase immobilization.
AB  - Organogels based on water-in-oil microemulsions can be formed using various
      natural polymers such as gelatin, agar or cellulose derivatives. Enzymes
      entrapped in the water core of the microemulsion can keep their activity and
      enhance their stability within the gel matrix. The importance of the
      microemulsion based organogels (MBGs) leans on their numerous potential
      biotechnological applications. An important example is the use of various lipase
      microemulsion systems for hydrolytic or synthetic reactions. In this review,
      several MBGs are being evaluated as immobilization matrices for various enzymes.
      The main subject focuses on the parameters that affect the use of MBGs as media
      for bioorganic reactions using lipases as catalysts.

PMID- 20156545
TI  - Strategies for the enhancement of recombinant protein production from mammalian
      cells by growth arrest.
AB  - Methods to increase the production of recombinant proteins in mammalian cell
      cultures have been developed which reduce in-culture growth through prohibiting
      progression of the cell cycle. This arrest increases the proportion of cells in
      the G1-phase of the cell cycle, and subsequently increases their specific
      productivity (Q(P)). Through careful balancing of the decreased growth rate with
      an increased Q(P), multi-fold increases in recombinant protein yield can be
      achieved. Induction of this arrest can occur through the addition of cytostatic
      chemical agents (NaBu or DMSO), over-expression of cell cycle inhibitory proteins
      (p21(Cip1) or p27(Kip1)), or through control of the culture environment (mild
      hypothermic temperatures). While all these controlled proliferation strategies
      have been developed independently, they all aim to control cell proliferation
      through a shared mechanism; the direct or indirect up-regulation of members of
      the cyclin-dependent kinase inhibitor (CKI) family. This review highlights the
      shared biology of these three controlled proliferation strategies, and their
      contribution towards bioprocess development for recombinant production from
      animal cell cultures.

PMID- 20156547
TI  - Para-phenylenediamine induced DNA damage and apoptosis through oxidative stress
      and enhanced caspase-8 and -9 activities in Mardin-Darby canine kidney cells.
AB  - Para-phenylenediamine (p-PD), a suspected carcinogen, is a component of permanent
      hair dyes. In this study we examined the mechanism of cytotoxicity and
      genotoxicity in Mardin-Darby canine kidney cells (MDCK)-treated with p-PD. Our
      results showed that p-PD decreased cell viability in a dose- and time-dependent
      manner. In addition, p-PD induced DNA damage was confirmed by the comet and TUNEL
      assays. Pre-treatment of MDCK cells with antioxidants vitamin C or E
      significantly inhibited p-PD induced cytotoxicity and reactive oxygen species
      (ROS) generation. Furthermore, p-PD induced apoptosis through activated initiator
      caspase-8 and -9, and effector caspase-3/7. Based on these results, we suggested
      that p-PD induce apoptosis which was mediated with caspase-8, caspase-9 and
      caspase-3/7 activation via the involvement of ROS.

PMID- 20156548
TI  - Partial characterization of the hemolytic activity of the nematocyst venom from
      the jellyfish Cyanea nozakii Kishinouye.
AB  - Using a recently developed technique to extract jellyfish venom from nematocysts,
      the present study investigated the hemolytic activity of Cyanea nozakii
      Kishinouye nematocyst venom on chicken erythrocytes. Venom extract caused a
      significant concentration-dependent hemolytic effect. The extract could retain
      its activity at -80 degrees C but was unstable when kept at 4 degrees C and -20
      degrees C for 2 days. The hemolytic activity was inhibited by heating within the
      range of 37-100 degrees C. The extract was active over a pH range of 5.0-8.63 and
      the pH optima for the extract was 7.8. Incubation of the venom with sphingomyelin
      specially inhibited hemolytic activity by up to 70%. Cu(2+) and Mn(2+) greatly
      reduced the hemolytic activity while Mg(2+), Sr(2+) and Ba(2+) produced a
      relatively low inhibiting effect on the hemolytic activity. Treatment with Ca(2+)
      induced a concentration-dependent increase in the hemolytic activity. In the
      presence of 5 mM EDTA, all the hemolytic activity was lost, however, the venom
      containing 1.5 mM EDTA was stable in the long-term storage. PLA(2) activity was
      also found in the nematocyst venom of C. nozakii. These characteristics provide
      us a fundamental knowledge in the C. nozakii nematocyst venom which would benefit
      future research.

PMID- 20156549
TI  - Transferability and inter-laboratory variability assessment of the in vitro
      bovine oocyte maturation (IVM) test within ReProTect.
AB  - The new European chemicals policy for the Registration, Evaluation, Authorization
      and Restriction of Chemicals (REACH) will most probably impose a dramatic
      increase in the number of animals required for reproductive toxicity testing. For
      this purpose, the development and validation of alternative methods is urgently
      needed in order to reduce the use of laboratory animals. The present study
      describes the inter-laboratory variability and the transferability assessment of
      an in vitro test able to identify chemical effects during the process of oocyte
      maturation in a bovine model. The test was developed/optimised within ReProTect,
      an integrated research project funded by the European Union, joining together 35
      partners with complementary expertise in reproductive toxicology. Eight chemicals
      with well-known toxic properties were tested (benzo[a]pyrene, busulfan, cadmium
      chloride, cycloheximide, diethylstilbestrol, ketoconazole, methylacetoacetate,
      mifepristone/RU-486 and DMSO as solvent) on the in vitro maturation (IVM) assay
      in two well-trained laboratories using the established Standard Operating
      Procedures. The statistical analysis demonstrated the concordance of results
      across the laboratories and the reproducibility of the test. We therefore
      conclude that the IVM test could advance toward the process of validation as
      alternative in vitro method that, in combination with additional in vitro tests,
      can become part of an integrated testing strategy in order to predict chemical
      hazards on mammalian fertility.

PMID- 20156550
TI  - Oxidative stress resistance in hippocampal cells is associated with altered
      membrane fluidity and enhanced nonamyloidogenic cleavage of endogenous amyloid
      precursor protein.
AB  - Reactive oxygen species (ROS) have important roles as signaling molecules in the
      regulation of a variety of biological processes. On the other hand, chronic
      oxidative stress exerted by ROS is widely considered a causative factor in aging.
      Therefore, cells need to be able to adapt to a chronic oxidative challenge and do
      so to a certain cell-type-specific extent. Recently, we have shown in oxidative
      stress-resistant cell lines, HT22(H2O2) and HT22(Glu), derived from the neuronal
      cell line HT22 by chronic exposure to sublethal concentrations of H(2)O(2) and
      glutamate, that, in addition to the known antioxidant defense mechanisms, e.g.,
      activation of antioxidant enzymes or up-regulation of heat-shock proteins,
      oxidative stress resistance depends on the composition of cellular membranes.
      Here, we extend our previous investigations and report increased membrane
      fluidity in HT22(H2O2) and HT22(Glu) cells compared to the parental HT22(WT)
      cells. The increased membrane fluidity correlates with a redistribution of
      cholesterol, sphingomyelin, and membrane-associated proteins involved in APP
      processing between detergent-resistant and detergent-soluble membrane subdomains.
      The altered membrane properties were associated with drastic changes in the
      metabolism of the Alzheimer disease-associated amyloid precursor protein (APP),
      particularly toward enhanced production of soluble APP alpha, which is a known
      neuroprotective factor. Thus our -data provide a link between chronic oxidative
      stress, alterations in membrane fluidity and composition of membrane subdomains,
      stress adaptation, and APP processing.

PMID- 20156551
TI  - Oxidative stress in skeletal muscle causes severe disturbance of exercise
      activity without muscle atrophy.
AB  - The increase in reactive oxygen species (ROS) levels that occurs during intense
      exercise has been proposed to be one of the major causes of muscle fatigue. In
      addition, the accumulation of cellular damage due to ROS is widely regarded to be
      one of the factors triggering age-related pathological conditions in skeletal
      muscle. To investigate the pathological significance of oxidative stress in
      skeletal muscle, we generated skeletal muscle-specific manganese superoxide
      dismutase-deficient (muscle-Sod2(-/-)) mice. The mutant mice showed severe
      disturbances in exercise activity, but no atrophic changes in their skeletal
      muscles. In histological and histochemical analyses, the mutant mice showed
      centralized nuclei in their muscle fibers and selective loss of enzymatic
      activity in mitochondrial respiratory chain complexes. In addition, the mutant
      mice displayed increased oxidative damage and reduced ATP content in their muscle
      tissue. Furthermore, a single administration of the antioxidant EUK-8
      significantly improved exercise activity and increased the cellular ATP level in
      skeletal muscle. These results imply that the superoxide anions generated in
      mitochondria play a pivotal role in the progression of exercise intolerance.

PMID- 20156552
TI  - Safe and targeted anticancer efficacy of a novel class of antioxidant-conjugated
      difluorodiarylidenyl piperidones: differential cytotoxicity in healthy and cancer
      cells.
AB  - The development of smart anticancer drugs that can selectively kill cancer cells
      while sparing the surrounding healthy tissues/cells is of paramount importance
      for safe and effective cancer therapy. We report a novel class of bifunctional
      compounds based on diarylidenyl piperidone (DAP) conjugated to an N
      hydroxypyrroline (NOH; a nitroxide precursor) group. We hypothesized that the DAP
      would have cytotoxic (anticancer) activity, whereas the NOH moiety would function
      as a tissue-specific modulator (antioxidant) of cytotoxicity. The study used four
      DAPs, namely H-4073 and H-4318 without NOH and HO-3867 and HO-4200 with NOH
      substitution. The goal of the study was to evaluate the proof-of-concept
      anticancer-versus-antioxidant efficacy of the DAPs using a number of cancerous
      (breast, colon, head and neck, liver, lung, ovarian, and prostate cancer) and
      noncancerous (smooth muscle, aortic endothelial, and ovarian surface epithelial)
      human cell lines. Cytotoxicity was determined using an MTT-based cell viability
      assay. All four compounds induced significant loss of cell viability in cancer
      cells, whereas HO-3867 and HO-4200 showed significantly less cytotoxicity in
      noncancerous cells. EPR measurements showed a metabolic conversion of the N
      hydroxylamine function to nitroxide with significantly higher levels of the
      metabolite and superoxide radical-scavenging (antioxidant) activity in
      noncancerous cells compared to cancer cells. Western blot analysis showed that
      the DAP-induced growth arrest and apoptosis in cancer cells were mediated by
      inhibition of STAT3 phosphorylation at the Tyr705 and Ser727 residues and
      induction of apoptotic markers of cleaved caspase-3 and PARP. The results suggest
      that the antioxidant-conjugated DAPs will be useful as safe and effective
      anticancer agents for cancer therapy.

PMID- 20156553
TI  - Changes in the expression of mitochondrial peroxiredoxin and thioredoxin in
      neurons and glia and their protective effects in experimental cerebral ischemic
      damage.
AB  - We observed chronological changes in the mitochondrial-specific antioxidant
      enzymes peroxiredoxin 3 (Prx3) and thioredoxin 2 (Trx2) and their neuroprotective
      effects in the hippocampal CA1 region after 5 min of transient cerebral ischemia
      in gerbils. In the sham-operated group, weak Prx3 and Trx2 immunoreactivity was
      detected in the stratum pyramidale. Prx3 immunoreactivity was increased in
      pyramidal neurons and expressed in microglia 1 and 3 days, respectively, after
      ischemia/reperfusion (I/R). Trx2 immunoreactivity in pyramidal neurons increased
      30 min and 1 day after I/R and decreased 6 h after I/R. Trx2 immunoreaction was
      expressed in astrocytes at 3 days postischemia. The intraventricular
      administration of Prx3 or Prx3/Trx2 (16 microg/20 microl, icv) using an osmotic
      pump significantly reduced ischemia-induced hyperactivity in a spontaneous motor
      test and protected CA1 pyramidal neurons from the ischemic damage. In addition,
      the activation of astrocytes and microglia was decreased in the ischemic CA1
      region after Prx3/Trx2 treatment. In addition, treatment with Prx3 or Prx3/Trx2
      significantly reduced lipid peroxidation and the release of cytochrome c from
      mitochondria and cytoplasm in the ischemic CA1 region. These results suggest that
      changes in the expression of Prx3 and Trx2 in the hippocampal CA1 region after
      I/R may be associated with the delayed neuronal death of CA1 pyramidal cells
      induced by transient cerebral ischemia, and that treatment with Prx3 or Prx3/Trx2
      in ischemic brains shows a potent neuroprotective effect against ischemic damage
      by reducing lipid peroxidation and mitochondrial-mediated apoptosis by I/R.

PMID- 20156555
TI  - Multidrug-resistant epidemic clones among bloodstream isolates of Pseudomonas
      aeruginosa in the Czech Republic.
AB  - To determine whether the high proportion of antimicrobial resistance among
      hospital isolates of Pseudomonas aeruginosa in the Czech Republic is associated
      with the spread of multidrug-resistant clones, we investigated 108 bloodstream
      isolates collected prospectively in 2007. The isolates originated from 48
      hospitals in 36 cities and were serotyped, tested for susceptibility to 10 anti
      Pseudomonas agents and studied by multilocus sequence typing, macrorestriction
      analysis and class 1 integron typing. Forty-five isolates were fully susceptible,
      while 14 and 49 isolates were resistant to 1-2 and 3-9 agents, respectively. A
      total of 42 multilocus sequence types (ST) were identified, of which ST235
      (serotype O11), ST175 (O4) and ST132 (O6) included 19, 16 and 5 isolates,
      respectively. These three STs encompassed 40 (82%) of 49 isolates resistant to
      more than two agents and originated from 29 hospitals in 22 cities. Isolates of
      the same ST had highly similar macrorestriction patterns. Twelve ST235 isolates
      harbored an integron variable region with the gene cassette array of aacA7-aadA6
      orfD, while 15 ST175 isolates shared a region with the aadB-aadA13 array and all
      ST132 isolates carried a region with aacA4. A carbapenemase-encoding gene
      (bla(IMP-7)) was detected in a single strain (ST357). In conclusion, the
      multidrug resistance of Czech P. aeruginosa bloodstream isolates in 2007 was
      predominantly associated with three epidemic clones, one of which belongs to
      international clonal complex CC235.

PMID- 20156554
TI  - Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase
      deficient mice during acute inflammation.
AB  - Acute inflammation is a common feature of many life-threatening pathologies,
      including septic shock. One hallmark of acute inflammation is the peroxidation of
      polyunsaturated fatty acids forming bioactive products that regulate
      inflammation. Myeloperoxidase (MPO) is an abundant phagocyte-derived hemoprotein
      released during phagocyte activation. Here, we investigated the role of MPO in
      modulating biologically active arachidonic acid (AA) and linoleic acid (LA)
      metabolites during acute inflammation. Wild-type and MPO-knockout (KO) mice were
      exposed to intraperitoneally injected endotoxin for 24 h, and plasma LA and AA
      oxidation products were comprehensively analyzed using a liquid chromatography
      mass spectrometry method. Compared to wild-type mice, MPO-KO mice had
      significantly lower plasma levels of LA epoxides and corresponding LA- and AA
      derived fatty acid diols. AA and LA hydroxy intermediates
      (hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids) were also
      significantly lower in MPO-KO mice. Conversely, MPO-deficient mice had
      significantly higher plasma levels of cysteinyl-leukotrienes with well-known
      proinflammatory properties. In vitro experiments revealed significantly lower
      amounts of AA and LA epoxides, LA- and AA-derived fatty acid diols, and AA and LA
      hydroxy intermediates in stimulated polymorphonuclear neutrophils isolated from
      MPO-KO mice. Our results demonstrate that MPO modulates the balance of pro- and
      anti-inflammatory lipid mediators during acute inflammation and, in this way, may
      control acute inflammatory diseases.

PMID- 20156556
TI  - Hedgehog signaling via angiopoietin1 is required for developmental vascular
      stability.
AB  - The molecular pathways by which newly formed, immature endothelial cell tubes
      remodel to form a mature network of vessels supported by perivascular mural cells
      are not well understood. The zebrafish iguana (igu) genetic mutant has a mutation
      in the daz-interacting protein 1 (dzip1), a member of the hedgehog signaling
      pathway. Loss of dzip1 results in decreased size of the cranial dorsal aortae,
      ultrastructural defects in perivascular mural cell recruitment and subsequent
      hemorrhage. Although hedgehog signaling is disrupted in igu mutants, we find no
      defects in vessel patterning or artery-vein specification. Rather, we show that
      the loss of angiopoietin1 (angpt1) expression in ventral perivascular mesenchyme
      is responsible for vascular instability in igu mutants. Over-expression of angpt1
      or partial down-regulation of the endogenous Angpt1 antagonist angpt2 rescues
      hemorrhage. This is the first direct in vivo link between hedgehog signaling and
      the induction of vascular stability by recruitment of perivascular mural cells
      through angiopoietin signaling.

PMID- 20156557
TI  - Vitamin D and breast cancer: inhibition of estrogen synthesis and signaling.
AB  - Calcitriol (1,25-dihydroxyvitamin D3), the hormonally active metabolite of
      vitamin D, inhibits the growth and induces the differentiation of many malignant
      cells including breast cancer (BCa) cells. Calcitriol exerts its anti
      proliferative activity in BCa cells by inducing cell cycle arrest and stimulating
      apoptosis. Calcitriol also inhibits invasion, metastasis and tumor angiogenesis
      in experimental models of BCa. Our recent studies show additional newly
      discovered pathways of calcitriol action to inhibit the growth of BCa cells.
      Calcitriol suppresses COX-2 expression and increases that of 15-PGDH thereby
      reducing the levels and biological activity of prostaglandins (PGs). Calcitriol
      decreases the expression of aromatase, the enzyme that catalyzes estrogen
      synthesis selectively in BCa cells and the breast adipose tissue surrounding BCa,
      by a direct repression of aromatase transcription via promoter II as well as an
      indirect effect due to the reduction in the levels and biological activity of
      PGE2, which is a major stimulator of aromatase transcription through promoter II
      in BCa. Calcitriol down-regulates the expression of estrogen receptor alpha and
      thereby attenuates estrogen signaling in BCa cells including the proliferative
      stimulus provided by estrogens. We hypothesize that the inhibition of estrogen
      synthesis and signaling by calcitriol and its anti-inflammatory actions will play
      an important role in the use of calcitriol for the prevention and/or treatment of
      BCa.

PMID- 20156558
TI  - 1alpha,25(OH)2-Vitamin D3 stimulation of secretion via chloride channel
      activation in Sertoli cells.
AB  - Sertoli cell secretory activities are highly dependent on ion channel functions
      and critical to spermatogenesis. The steroid hormone 1alpha,25(OH)2-vitamin D3
      (1,25(OH)2-D3) stimulates exocytosis in different cell systems by activating a
      nongenotropic vitamin D receptor (VDR). Here, we described 1,25(OH)2-D3
      stimulation of secretion via Cl(-) channel activation in the mouse immature
      Sertoli cell line TM4. 1,25(OH)2-D3 potentiation of chloride currents was
      dependent on hormone concentration, and correlated with a significant increase in
      whole-cell capacitance within 20-40 min. In addition, Cl(-) currents were
      potentiated by the nongenomic VDR agonist 1alpha,25(OH)2 lumisterol D3 (JN),
      while 1,25(OH)2-D3 potentiation of channels was suppressed by nongenomic VDR
      antagonist 1beta,25(OH)2-vitamin D3 (HL). Treatment of TM4 cells with PKC and PKA
      activators PMA and forskolin respectively, increased Cl(-) currents
      significantly, while PKC and PKA inhibitors Go6983 and H-89, respectively,
      abolished 1,25(OH)2-D3 stimulation of Cl(-) currents, suggesting phosphorylation
      pathways in 1,25(OH))2-D3 mediated channel responses. RT-PCR demonstrated the
      expression of outwardly rectifying ClC-3 channels in TM4 cells. Taken together,
      our results demonstrate a PKA/PKC-dependent 1,25(OH)2-D3/VDR nongenotropic
      pathway leading to Cl(-) channel and exocytosis activation in Sertoli cells. We
      conclude that 1,25(OH)2-D3 appears to be a modulator of male reproductive
      functions at least in part by stimulating Sertoli cell secretory functions.

PMID- 20156559
TI  - The endocannabinoid 2-arachidonoylglycerol reduces lesion expansion and white
      matter damage after spinal cord injury.
AB  - A series of pathological events secondary to spinal cord injury (SCI) contribute
      to the spread of the damage, which aggravates neurological deficits. Here we
      report that a single dose of the neuroprotective endocannabinoid 2-arachidonoyl
      glycerol (2-AG) administered early after SCI reduces lesion expansion, which was
      prevented by simultaneous blockade of both CB1 and CB2 receptors but not by
      blockade of either receptor alone. Treatment with 2-AG also preserves the white
      matter around the epicenter of the injury. Moreover, in the preserved white
      matter, 2-AG protects myelin from damage and reduces oligodendrocyte loss. In
      addition to these protective actions at the epicenter region, 2-AG also inhibits
      the myelin damage and delayed oligodendrocyte loss induced at 10mm from the
      epicenter. Interestingly, the early protective action of 2-AG is maintained 28
      days after injury, when the lesion size is still smaller and the preservation of
      white matter is better in 2-AG-treated animals. Therefore, our results show that
      2-AG protects from the expansion of the lesion and white matter damage, which
      suggest that this endogenous cannabinoid may be useful as a protective treatment
      for acute SCI.

PMID- 20156560
TI  - Promotion and regulation of homologous recombination by DNA helicases.
AB  - In eukaryotes, homologous recombination (HR) provides an important means to
      eliminate DNA double-stranded breaks and other chromosomal lesions. Accordingly,
      failure in HR leads to genomic instability and a predisposition to various cancer
      types. While HR is clearly beneficial for genome maintenance, inappropriate or
      untimely events can be harmful. For this reason, HR must be tightly regulated.
      Several DNA helicases contribute to HR regulation, by way of mechanisms that are
      conserved from yeast to humans. Mutations in several HR-specific helicases e.g.
      BLM and RECQ5, are either associated with cancer-prone human syndromes or
      engender the cancer phenotype in animal models. Therefore, delineating the role
      of DNA helicases in HR regulation has direct relevance to cancer etiology.
      Genetic, cytological, biochemical, and other analyses have shown that DNA
      helicases participate in early or late stages of HR, to disrupt nucleoprotein
      filaments that harbor the Rad51 recombinase or dissociate the D-loop intermediate
      made by Rad51, or to prevent undesirable events and/or minimize potentially
      deleterious crossover products. Moreover, the ensemble that harbors BLM and
      topoisomerase IIIalpha can dissolve the double-Holliday junction, a complex DNA
      intermediate generated during HR, to produce non-crossover products. These
      regulatory pathways function in parallel to promote the usage of the genome
      preserving synthesis-dependent strand annealing HR pathway or otherwise suppress
      crossover formation.

PMID- 20156561
TI  - Laminin chain assembly is regulated by specific coiled-coil interactions.
AB  - Laminins are large heterotrimeric, multidomain proteins that play a central role
      in organising and establishing all basement membranes. Despite a total of 45
      potential heterotrimeric chain combinations formed through the coiled-coil domain
      of the 11 identified laminin chains (alpha1-5, beta1-3, gamma1-3), to date only
      15 different laminin isoforms have been reported. This observation raises the
      question whether laminin assembly is regulated by differential gene expression or
      specific chain recognition. To address this issue, we here perform a complete
      analysis of laminin chain assembly and specificity. Using biochemical and
      biophysical techniques, all possible heterotrimeric combinations from recombinant
      C-terminal coiled-coil fragments of all chains were analysed. Apart from laminin
      323 (alpha3, beta2, gamma3), for which no biochemical evidence of its existence
      in vivo is available, these experiments confirmed all other known laminin
      isoforms and identified two novel potential chain combinations, laminins 312
      (alpha3, beta1, gamma2) and 422 (alpha4, beta2, gamma4). Our findings contribute
      to the understanding of basement membrane structure, function and diversity.

PMID- 20156562
TI  - Expression and characterization of a constitutively active STAT6 from Tetraodon.
AB  - In this paper, we report the cloning and characterization of the STAT6 gene from
      the pufferfish, Tetraodon nigroviridis. The TnSTAT6 gene is composed of 20 exons
      and 19 introns. The exon-intron organization of this gene is similar to that of
      HsSTAT6 except for the exons encoding the C-terminal transactivation domain. The
      full-length complementary (c)DNA of TnSTAT6 encodes a 794-amino acid protein that
      is 31% identical to human STAT6. We generated a constitutively active TnSTAT6-JH1
      by fusing the kinase domain of carp JAK1 to the C-terminal end of TnSTAT6 and
      demonstrated that the fusion protein has specific DNA-binding ability and can
      activate a reporter construct carrying multiple copies of mammalian IL-4-response
      elements. Interestingly, TnSTAT6-JH1 associated with and phosphorylated TnSTAT6
      on Tyr661. Mutation of this residue, Y661W, in TnSTAT6 abolished its association
      with TnSTAT6-JH1. This is consistent with the importance of the corresponding
      Tyr641 of HsSTAT6 in tyrosine phosphorylation and dimer formation. On the other
      hand, treatment of mammalian IL-4 did not induce tyrosine phosphorylation of wild
      type TnSTAT6, suggesting that both the divergent N-terminal domain and coiled
      coiled domain of TnSTAT6 may affect the interaction of TnSTAT6 with mammalian IL
      4 receptor complexes.

PMID- 20156563
TI  - Expression and characterization of the JAK kinase and STAT protein from brine
      shrimp, Artemia franciscana.
AB  - In this study, we isolated and characterized both JAK and STAT genes from
      Artemia, Artemia franciscana. Although AfJAK showed only 19% identity (33%
      similarity) to the Drosophila Hop protein, AfJAK contained the characteristic JAK
      homology domain (JH domain) from JH1 to JH7. On the other hand, AfSTAT showed
      higher identity (30%) to Drosophila STAT (STAT92E). The low identities of AfJAK
      and AfSTAT to Drosophila Hop and STAT92E suggest that JAK and STAT proteins are
      unique in each different species of invertebrate. RT-PCR analysis showed that
      both AfJAK and AfSTAT transcripts were ubiquitously expressed in the embryo,
      which is similar to the expression patterns of Drosophila Hop and STAT92E mRNAs
      during development. In addition, we generated a constitutively active form of
      AfSTAT by fusing the JH1 domain of AfJAK to the C-terminal end of AfSTAT. This
      fusion protein, AfSTAT-HA-JH1, autophosphorylated on its tyrosine residue and was
      able to bind to specific DNA motifs including the STAT-binding motifs in the
      Drosophila Raf promoter. Both AfJAK and AfSTAT proteins elicited the
      transactivation potential toward the fly Raf promoter in Sf9 cells. However,
      tyrosine phosphorylation of AfSTAT was not detected, which is consistent with the
      cellular localization analysis that most AfSTAT proteins were in the cytoplasm.
      Our results demonstrate that both JAK and STAT are present in the genome of
      Artemia, which can serve as the basis for further investigations to explore the
      role of the JAK/STAT signal pathway in the development and immune response of
      brine shrimp.

PMID- 20156564
TI  - In vivo definition of parieto-motor connections involved in planning of grasping
      movements.
AB  - We combined bifocal transcranial magnetic stimulation (TMS) and diffusion tensor
      imaging (DTI) tractography to investigate in humans the contribution of
      connections originating from different parietal areas in planning of different
      reaching to grasp movements. TMS experiments revealed that in the left hemisphere
      functional connectivity between the primary motor cortex (M1) and a portion of
      the angular gyrus (AG) close to the caudal intraparietal sulcus was activated
      during early preparation of reaching and grasping movements only when the
      movement was made with a whole hand grasp (WHG) towards objects in contralateral
      space. In contrast, a different pathway, linking M1 with a part of the
      supramarginal gyrus (SMG) close to the anterior intraparietal sulcus, was
      sensitive only to the type of grasp required (precision grasping) but not to the
      position of the object in space. A triple coil experiment revealed that
      inactivation of the ventral premotor area (PMv) by continuous theta burst
      stimulation interfered with some of these interactions. Anatomical DTI
      tractography revealed that AG and SMG are strongly connected with PMv and with M1
      by different bundles of the superior longitudinal fasciculus (SLF). These results
      demonstrate the existence of segregated parieto-premotor-motor pathways crucial
      for preparation of different grasping actions and indicate that these may process
      information relevant to both the position of the object and the hand shape
      required to use it.

PMID- 20156565
TI  - Neurophysiological markers of novelty processing are modulated by COMT and DRD4
      genotypes.
AB  - Humans are faced with the dilemma to maintain a stable cognitive set on the one
      hand and to be able to redirect and switch attention to novel stimuli of
      potential importance. The dopaminergic system has been implicated in the balance
      between these two antagonistic constraints and in particular in novelty
      processing. Here we studied the impact of two polymorphisms affecting
      dopaminergic functioning (COMT Val108/158Met and DRD4 SNP -521) on
      neurophysiological correlates of novelty processing. Recording event-related
      potentials (ERPs) and oscillatory activity in a modified oddball task that
      featured infrequent but task-irrelevant novel sounds in addition to frequent
      standard and rare target tones, we examined participants homozygous for the Met
      or Val variant of COMT as well as homozygous for the C or T variant of DRD4. We
      found effects mainly on the P3a component to novel stimuli. A greater P3a
      amplitude was found for the COMT-ValVal group relative to MetMet. There was a
      tendency for DRD4-TT participants to show greater P3a amplitude and shorter P3a
      latency. Finally, DRD4-TT and COMT-ValVal participants showed the greatest
      increase of theta-power to novel stimuli. By contrast, the P3b component to
      target stimuli showed little influence of the studied polymorphism. Individual
      differences in dopaminergic genes explain part of the interindividual variance in
      the neural correlates of novelty but not target processing.

PMID- 20156566
TI  - Shape analysis of the neostriatum in frontotemporal lobar degeneration,
      Alzheimer's disease, and controls.
AB  - BACKGROUND AND PURPOSE: Frontostriatal circuit mediated cognitive dysfunction has
      been implicated in frontotemporal lobar degeneration (FTLD), but not Alzheimer's
      disease, or healthy aging. We measured the neostriatum (caudate nucleus and
      putamen) volume in FTLD (n=34), in comparison with controls (n=27) and
      Alzheimer's disease (AD, n=19) subjects. METHODS: Diagnoses were based on
      international consensus criteria. Manual bilateral segmentation of the caudate
      nucleus and putamen was conducted blind to diagnosis by a single analyst, on MRI
      scans using a standardized protocol. Intra-cranial volume was calculated via a
      stereological point counting technique and was used for scaling the shape
      analysis. The manual segmentation binaries were analyzed using UNC Shape Analysis
      tools (University of North Carolina) to perform comparisons among FTLD, AD, and
      controls for global shape, local p-value significance maps, and mean magnitude of
      shape displacement. RESULTS: Shape analysis revealed that there was significant
      shape difference between FTLD, AD, and controls, consistent with the predicted
      frontostriatal dysfunction and of significant magnitude, as measured by
      displacement maps. There was a lateralized difference in shape for the left
      caudate for FTLD compared to AD; non-specific global atrophy in AD compared to
      controls; while FTLD showed a more specific pattern in regions relaying fronto-
      and corticostriatal circuits. CONCLUSIONS: Shape analysis shows regional
      specificity of atrophy, manifest as shape deflation, with implications for
      frontostriatal and corticostriatal motoric circuits, in FTLD, AD, and controls.

PMID- 20156567
TI  - Extracting the internal representation of faces from human brain activity: an
      analogue to reverse correlation.
AB  - Much of the debate surrounding the precise functional role of brain mechanisms
      implicated in the processing of human faces can be explained when considering
      that studies into early-stage neural representations of the spatial arrangement
      of facial features are potentially contaminated by "higher-level" cognitive
      attributes associated with human faces. One way to bypass such attributes would
      be to employ ambiguous stimuli that are not biased toward any particular object
      class and analyze neural activity in response to those stimuli in a manner
      similar to traditional reverse correlation for mapping visual receptive fields.
      Accordingly, we sought to derive whole face representations directly from neural
      activity in the human brain using electroencephalography (EEG). We presented
      ambiguous fractal noise stimuli to human participants and asked them to rate each
      stimulus along a "face not present" to "face present" continuum while
      simultaneously recording EEGs. All EEGs were subjected to a time-frequency
      analysis near 170 ms (negative amplitudes near 170 ms post-stimulus onset have
      been linked to early face processing) for five different frequency bands (delta,
      theta, alpha, beta, and gamma) on a trial-by-trial basis, independent of the
      behavioral responses. Images containing apparent face-like structure were
      obtained for theta through gamma frequency bands for strong negative amplitudes
      near 170 ms post-stimulus onset. The presence of the face-like structure in the
      spatial images derived from brain signals was objectively verified using both
      Fourier methods and trained neural networks. The results support the use of a
      modified reverse correlation technique with EEG as a non-biased assessment of
      brain processes involved in the complex integration of spatial information into
      objects such as human faces.

PMID- 20156568
TI  - Modulation of hypothalamus and amygdalar activation levels with stimulus valence.
AB  - In spite of long-standing evidence showing that the hypothalamus is instrumental
      in generating behaviors associated with positive and negative emotions, little is
      known about the role of the hypothalamus in normal human emotional processing.
      Recent findings have suggested that the hypothalamus plays a role beyond mere
      control of HPA-axis function; this is also supported by the existence of rich
      anatomical connections between the hypothalamus and the amygdala, a region known
      for its important role in emotional processing. However, evidence of emotion
      induced hypothalamic activity from neuroimaging studies has been inconsistent,
      possibly due to methodological limitations (e.g., low spatial resolution). Taking
      advantage of recent improvements in fMRI technology we set out to explore a
      possible valence-dependent modulation of hypothalamic activity. Using second
      order parametric analysis of high-resolution BOLD fMRI, we assessed hypothalamic
      activation patterns during passive viewing of visual stimuli of varying valence,
      and compared the results with the activity pattern in the amygdalae, i.e. nuclei
      with known valence-dependent activity profiles. We show that both hypothalamic
      and amygdalar activation is modulated by the second-order stimulus valence term,
      i.e., there is increased neural activity following the processing of both
      positive and negative stimuli. Our results suggest that the hypothalamus may
      serve a role in generating emotions broader than generally assumed.

PMID- 20156569
TI  - The effects of age and sex on cortical sulci in the elderly.
AB  - A large number of structural brain studies using magnetic resonance imaging (MRI)
      have reported age-related cortical changes and sex difference in brain
      morphology. Most studies have focused on cortical thickness or density, with
      relatively few studies of cortical sulcal features, especially in the elderly. In
      this paper, we report global sulcal indices (g-SIs) of both cerebral hemispheres
      and the average sulcal span in six prominent sulci, as observed in T1-weighted
      scans obtained from a large community cohort of 319 non-demented individuals aged
      between 70 and 90 years (mean=78.06+/-4.75; male/female=149/170), using automated
      methods. Our results showed that for both hemispheres, g-SIs had significant
      negative correlations with age in both men and women. Using an interactive effect
      analysis, we found that g-SIs for men declined faster with age than that for
      women. The widths of all six sulcal spans increased significantly with age, with
      largest span increase occurring in the superior frontal sulcus. Compared to
      women, men had significantly wider sulcal spans for all sulci that were examined.
      Our findings suggest that both age and sex contribute to significant cortical
      gyrification differences and variations in the elderly. This study establishes a
      reference for future studies of age-related brain changes and neurodegenerative
      diseases in the elderly.

PMID- 20156571
TI  - Effects of low-field magnetic stimulation on brain glucose metabolism.
AB  - Echo planar imaging (EPI), the gold standard technique for functional MRI (fMRI),
      is based on fast magnetic field gradient switching. These time-varying magnetic
      fields induce electric (E) fields in the brain that could influence neuronal
      activity; but this has not been tested. Here we assessed the effects of EPI on
      brain glucose metabolism (marker of brain function) using PET and 18F 2-fluoro-2
      deoxy-D-glucose ((18)FDG). Fifteen healthy subjects were in a 4 T magnet during
      the (18)FDG uptake period twice: with (ON) and without (OFF) EPI gradients pulses
      along the z-axis (G(z): 23 mT/m; 250 mus rise-time; 920 Hz). The E-field from
      these EPI pulses is non-homogeneous, increasing linearly from the gradient's
      isocenter (radial and z directions), which allowed us to assess the correlation
      between local strength of the E-field and the regional metabolic differences
      between ON and OFF sessions. Metabolic images were normalized to metabolic
      activity in the plane positioned at the gradient's isocenter where E=0 for both
      ON and OFF conditions. Statistical parametric analyses used to identify regions
      that differed between ON versus OFF (p<0.05, corrected) showed that the relative
      metabolism was lower in areas at the poles of the brain (inferior occipital and
      frontal and superior parietal cortices) for ON than for OFF, which was also
      documented with individual region of interest analysis. Moreover the magnitude of
      the metabolic decrements was significantly correlated with the estimated strength
      of E (r=0.68, p<0.0001); the stronger the E-field the larger the decreases.
      However, we did not detect differences between ON versus OFF conditions on mood
      ratings nor on absolute whole brain metabolism. This data provides preliminary
      evidence that EPI sequences may affect neuronal activity and merits further
      investigation.

PMID- 20156570
TI  - Imaging genetics of mood disorders.
AB  - Mood disorders are highly heritable and have been linked to brain regions of
      emotion processing. Over the past few years, an enormous amount of imaging
      genetics studies has demonstrated the impact of risk genes on brain regions and
      systems of emotion processing in vivo in healthy subjects as well as in mood
      disorder patients. While sufficient evidence already exists for several
      monaminergic genes as well as for a few non-monoaminergic genes, such as brain
      derived neurotrophic factor (BDNF) in healthy subjects, many others only have
      been investigated in single studies so far. Apart from these studies, the present
      review also covers imaging genetics studies applying more complex genetic disease
      models of mood disorders, such as epistasis and gene-environment interactions,
      and their impact on brain systems of emotion processing. This review attempts to
      provide a comprehensive overview of the rapidly growing field of imaging genetics
      studies in mood disorder research.

PMID- 20156573
TI  - Association of individual resting state EEG alpha frequency and cerebral blood
      flow.
AB  - Cognitive task performance differs considerably between individuals. Besides
      cognitive capacities, attention might be a source of such differences. The
      individual's EEG alpha frequency (IAF) is a putative marker of the subject's
      state of arousal and attention, and was found to be associated with task
      performance and cognitive capacities. However, little is known about the
      metabolic substrate (i.e. the network) underlying IAF. Here we aimed to identify
      this network. Correlation of IAF with regional Cerebral Blood Flow (rCBF) in
      fifteen young healthy subjects revealed a network of brain areas that are
      associated with the modulation of attention and preparedness for external input,
      which are relevant for task execution. We hypothesize that subjects with higher
      IAF have pre-activated task-relevant networks and thus are both more efficient in
      the task-execution, and show a reduced fMRI-BOLD response to the stimulus, not
      because the absolute amount of activation is smaller, but because the additional
      activation by processing of external input is limited due to the higher baseline.

PMID- 20156572
TI  - Salivary cortisol and prefrontal cortical thickness in middle-aged men: A twin
      study.
AB  - Although glucocorticoid receptors are highly expressed in the prefrontal cortex,
      the hippocampus remains the predominant focus in the literature examining
      relationships between cortisol and brain. We examined phenotypic and genetic
      associations of cortisol levels with the thickness of prefrontal and anterior
      cingulate cortex regions, and with hippocampal volume in a sample of 388 middle
      aged male twins who were 51-59 years old. Small but significant negative
      phenotypic associations were found between cortisol levels and the thickness of
      left dorsolateral (superior frontal gyrus, left rostral middle frontal gyrus) and
      ventrolateral (pars opercularis, pars triangularis, pars orbitalis) prefrontal
      regions, and right dorsolateral (superior frontal gyrus) and medial orbital
      frontal cortex. Most of the associations remained significant after adjusting for
      general cognitive ability, cardiovascular risk factors, and depression. Bivariate
      genetic analyses suggested that some of the associations were primarily accounted
      for by shared genetic influences; that is, some of the genes that tend to result
      in increased cortisol levels also tend to result in reduced prefrontal cortical
      thickness. Aging has been associated with reduced efficiency of hypothalamic
      pituitary-adrenal function, frontal lobe shrinkage, and increases in health
      problems, but our present data do not allow us to determine the direction of
      effects. Moreover, the degree or the direction of the observed associations and
      the extent of their shared genetic underpinnings may well change as these
      individuals age. Longitudinal assessments are underway to elucidate the direction
      of the associations and the genetic underpinnings of longitudinal phenotypes for
      changes in cortisol and brain morphology.

PMID- 20156574
TI  - Kinetic modelling using basis functions derived from two-tissue compartmental
      models with a plasma input function: general principle and application to
      [18F]fluorodeoxyglucose positron emission tomography.
AB  - A kinetic modelling method for the determination of influx constant, Ki is given
      that utilises basis functions derived from plasma input two-tissue compartmental
      models (BAFPIC). Two forms of the basis functions are given: BAFPICI with k4=0
      (no product loss) and BAFPICR with k4 non-zero. Simulations were performed using
      literature rate constant values for [18F]fluorodeoxyglucose (FDG) in both normal
      and abnormal brain pathology. Both homogeneous and heterogeneous tissues were
      simulated and this data was also used as input for other methods commonly used to
      determine Ki: non-linear least squares compartmental modelling (NLLS),
      autoradiographic method and Patlak-Gjedde graphical analysis (PGA). The four
      methods were also compared for real FDG positron emission tomography (PET) data.
      For both k4=0 and k4 non-zero simulated data BAFPIC had the best bias properties
      of the four methods. The autoradiographic method was always the best for
      variability but BAFPICI had lower variability than PGA and NLLS. For non-zero k4
      data, the variance of BAFPICR was inferior to PGA but still significantly
      superior to NLLS. Ki maps calculated from real data substantiate the simulation
      results, with BAFPICI having lower noise than PGA. Voxel Ki values from BAFPICI
      correlated well with those from PGA (r2=0.989). BAFPIC is easy to implement and
      combines low bias with good noise properties for voxel-wise determination of Ki
      for FDG. BAFPIC is suitable for determining Ki for other tracers well
      characterised by a serial two-tissue compartment model and has the advantage of
      also producing values for individual kinetic constants and blood volume.

PMID- 20156575
TI  - Similar cerebral networks in language, music and song perception.
AB  - Two fMRI experiments were conducted using song to investigate the domain
      specificity of linguistic and musical processing. In Experiment 1, participants
      listened to pairs of spoken words, "vocalise" (i.e., singing without words), and
      sung words while performing a same-different task. Results revealed bilateral
      involvement of middle and superior temporal gyri and inferior and middle frontal
      gyri while listening to spoken words, sung words and vocalise, although to
      different degrees. In Experiment 2, participants listened to pairs of sung words
      that were similar or different in terms of the linguistic and musical dimensions
      (2x2 factorial event-related design) while performing a same-different task.
      Results showed widespread interactions between the linguistic and musical
      dimensions of sung words mainly within the network of brain areas identified in
      Experiment 1. Consequently, the activity in these brain regions cannot be
      considered as specific to either language or music processing. Taken together,
      results of both experiments argue against domain specificity and provide
      additional evidence for a common cerebral network involved in both
      lexical/phonological and melodic processing.

PMID- 20156576
TI  - Influence of anisotropic electrical conductivity in white matter tissue on the
      EEG/MEG forward and inverse solution. A high-resolution whole head simulation
      study.
AB  - To investigate the influence of anisotropic electrical conductivity in white
      matter on the forward and inverse solution in electroencephalography (EEG) and
      magnetoencephalography (MEG) numerical simulation studies were performed. A high
      resolution (1 mm3 isotropic) finite element model of a human head was implemented
      to study the sensitivity of EEG and MEG source localization. In vivo information
      on the anisotropy was obtained from magnetic resonance diffusion tensor imaging
      and included into the model, whereas both a direct transformation and a direct
      transformation with volume normalization were used to obtain conductivity
      tensors. Additionally, fixed artificial anisotropy ratios were also used, while
      considering only the orientation information from DTI, to generate conductivity
      tensors. Analysis was performed using over 25,000 single dipolar sources covering
      the full neocortex. Major findings of the study include that EEG is more
      sensitive to anisotropic conductivities in white matter compared to MEG.
      Especially with the inverse analysis, we found that sources placed deep in sulci
      are located more laterally if anisotropic conductivity of white matter tissue is
      neglected. Overall, the single-source localization errors resulting from a
      neglect of anisotropy were found to be smaller compared to errors associated with
      other modeling errors, like misclassified tissue or the use of nonrealistic head
      models. In contrast to the small localization error we observed significant
      changes in magnitude and orientation. The latter is important since dipole
      orientation might be more important than absolute dipole localization in
      assigning, e.g., epileptic activity to the wall of the affected brain sulcal
      area. If high-resolution finite element models are used to perform source
      localization in EEG and MEG experiments and the quality of the measured data
      permits localization accuracy of 1 mm and below, the influence of anisotropic
      compartments has to be taken into account.

PMID- 20156577
TI  - Assessment of ECG interval and restitution parameters in the canine model of
      short QT syndrome.
AB  - INTRODUCTION: The short QT syndrome (SQTS) is characterized by a short QT
      interval resulting from accelerated ventricular repolarization, and may be
      associated with ventricular fibrillation but not torsades de pointes. There are
      abundant data on the adverse effects of long QT, but knowledge of SQTS is sparse.
      The aim of this study was to examine whether analyses of several ECG biomarkers
      (QT, QTcB, QTcF, QTcV, QT(btb), and QT(RR1000)) and dynamic restitution of the
      beat-to-beat QT-TQ relationship (TQ(min), %QT/TQ ratio>1, QT/TQ ratio(max)) can
      be used to assess ECG changes in conscious dogs. METHODS: Sling-trained dogs were
      infused with escalating concentration of levcromakalim (0, 1.0, 3.3, and 10.0
      microg/kg/min), pinacidil (0, 3.3, 10.0, and 33.3 microg/kg/min), and nicorandil
      (0, 0.03, 0.1, and 0.3 mg/kg/min), drugs known to shorten QT. The RR, QT, QTcB,
      QTcF, QTcV, QT(RR1000), and TQ were measured before and after each concentration
      of the QT shortening test compounds. RESULTS: Levcromakalim, pinacidil, and
      nicorandil but not vehicle significantly shortened RR, QT, QT(btb), QT(RR1000),
      and TQ but not QTc(B,F,V). The QT-RR cloud also shifted to the lower bounds of
      the normal QT-RR boundary by the test compounds. The percentage of beats with a
      QT/TQ ratio>1 was significantly increased in a dose response manner with
      levcromakalim and pinacidil and the lower TQ interval boundary (5th percentile)
      was decreased when compared to baseline or vehicle. DISCUSSION: QT(btb),
      QT(RR1000), and dynamic beat-to-beat measurements of restitution constitute
      clinically applicable ECG biomarkers for assessment of changes associated with
      arrhythmogenic risk of ventricular fibrillation due to QT abbreviation.

PMID- 20156578
TI  - Nitric oxide in the hypothalamus-pituitary axis mediates increases in brain
      glucose retention induced by carotid chemoreceptor stimulation with cyanide in
      rats.
AB  - Neuronal nitric oxide synthase (nNOS), which catalyzes the generation of nitric
      oxide (NO), is expressed by neuron subpopulations in the CNS. Nitric oxide is
      involved in neurotransmission and central glucose homeostasis. Our prior studies
      have shown that carotid body receptors participate in brain glucose regulation in
      vivo, and suggest the presence of a NO tonic mechanism in the solitary tract
      nucleus (STn). However, the role of NO within STn in glucose control remains
      unknown. In this study, we explored the potential regulatory role of NO on brain
      glucose retention induced by carotid body chemoreceptor anoxic stimulation with
      sodium cyanide (NaCN) which inhibits oxidative metabolism. Intracisternal
      infusions of nitroxidergic drugs before carotid chemoreceptor stimulation in
      anesthetized rats, elicited changes in nitrite concentration in plasma and
      hypothalamus-pituitary (H-P) tissue, as well as in gene expression of neuronal
      and inducible isoforms (nNOS and iNOS) in H-P tissue. The changes observed in
      above variables modified brain glucose retention in an opposite direction. When
      the NO donor, sodium nitroprusside (SNP), was given before carotid stimulation,
      nitrite concentration in plasma and H-P tissue, and gene expression of nNOS and
      iNOS in H-P tissue increased, whereas brain glucose retention decreased. In
      contrast, when the NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME)
      was infused immediately before carotid chemoreceptor stimulation, nitrite levels
      and nNOS expression decreased in plasma and H-P tissue, whereas brain glucose
      retention increased. Anoxic stimulation by itself induced an increase in the
      expression of both genes studied. All these results indicate that de novo
      expression of the nNOS gene in H-P tissue may be critically involved in central
      glucose changes observed after anoxic carotid chemoreceptor stimulation in
      conjunction with NO.

PMID- 20156579
TI  - Formyl peptide receptor-mediated proinflammatory consequences of peptide
      deformylase inhibition in Staphylococcus aureus.
AB  - The biosynthesis of proteins with N-terminal formylated methionine residues and
      subsequent protein deformylation are unique and invariant bacterial processes.
      They are exploited by the capacity of the human innate immune system to sense
      formylated peptides (FPs) and targeted by the deformylation-blocking antibiotic
      actinonin. We show that human polymorphonuclear leukocytes respond via the formyl
      peptide receptor (FPR) with increased calcium ion fluxes, chemotactic migration,
      IL-8 release, and CD11b upregulation to the human pathogen Staphylococcus aureus
      upon actinonin treatment. These data underscore the crucial role of bacterial FPs
      in innate immunity and indicate that deformylase inhibition may have considerable
      proinflammatory consequences.

PMID- 20156580
TI  - Peroxisome proliferator-activated receptors gamma reverses hepatic nutritional
      fibrosis in mice and suppresses activation of hepatic stellate cells in vitro.
AB  - Nonalcoholic steatohepatitis with fibrosis is a more severe form of nonalcoholic
      fatty liver disease, one of the most common liver diseases. We have previously
      shown that peroxisome proliferator-activated receptors gamma (PPARgamma) ligand,
      rosiglitazone, prevented the development of the methionine choline deficient
      (MCD) diet-induced fibrosing steatohepatitis. We have now tested whether
      overexpression of PPARgamma ameliorates established steatohepatitis and fibrosis.
      Male C57BL6 mice fed with MCD diet for 8 weeks developed hepatic fibrosis with
      increased hepatic expression of collagen1alpha(I), inhibitors of fibrosis
      reversal-1, regulator involved in matrix degradation-9 and connective tissue
      growth factor. After 2 weeks of transduction of PPARgamma through an adenovirus
      expressing PPARgamma (Ad-PPARgamma), expression of these genes was reduced in a
      manner that paralleled the reduction in activated hepatic stellate cells (HSCs)
      and resolution of liver fibrosis. On the in vitro study, PPARgamma is expressed
      in primary quiescent HSC, but depleted in culture activated HSC. Conversely,
      ectopic expression of PPARgamma in activated HSC achieved the phenotypic reversal
      to the quiescent cell. Such induction markedly suppressed cell viability and cell
      proliferation, downregulated proliferating cell nuclear antigen, and caused cell
      cycle arrest at G0/G1 phase. Further, introduction of PPARgamma in HSC increased
      cell apoptosis, this was confirmed by enhanced expression of FasL, cleaved
      caspase-3, cleaved caspase-7 and poly ADP-ribose polymerase, indicating an
      extrinsic apoptosis pathway. In conclusion, the present study shows that MCD diet
      induced fibrosing steatohepatitis can be reversed by overexpression of PPARgamma.
      It is likely that PPARgamma reverses fibrosis by reducing HSCs proliferation,
      inducing cell cycle arrest and apoptosis.

PMID- 20156581
TI  - Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor
      cells.
AB  - Cell proliferation only proceeds when metabolism is capable of providing a budget
      of metabolic intermediates that is adequate to ensure both energy regeneration
      and the synthesis of cell building blocks in sufficient amounts. In tumor cells,
      the glycolytic pyruvate kinase isoenzyme M2 (PKM2, M2-PK) determines whether
      glucose is converted to lactate for regeneration of energy (active tetrameric
      form, Warburg effect) or used for the synthesis of cell building blocks (nearly
      inactive dimeric form). This review discusses the regulation mechanisms of
      pyruvate kinase M2 expression by different transcription factors as well as the
      regulation of pyruvate kinase M2 activity by direct interaction with certain
      oncoproteins, tyrosine and serine phosphorylation, binding of phosphotyrosine
      peptides, association with other glycolytic and non glycolytic enzymes, the
      promyelocytic leukemia tumor suppressor protein, as well as metabolic
      intermediates. An intervention in the regulation mechanisms of the expression,
      activity and tetramer to dimer ratio of pyruvate kinase M2 has severe
      consequences for metabolism as well as proliferation and tumorigenic capacity of
      the cells which makes this enzyme a promising target for potential therapeutic
      approaches. The quantification of the dimeric form of pyruvate kinase M2 (Tumor
      M2-PK) in plasma and stool allows early detection of tumors and therapy control.
      Several different mechanisms may induce a translocation of pyruvate kinase M2
      into the nucleus. The role of pyruvate kinase M2 in the nucleus is complex as
      witnessed by evidence of its effect both as pro-proliferative as well as pro
      apoptotic stimuli.

PMID- 20156582
TI  - Hexafluoroisopropanol-induced helix-sheet transition of stem bromelain:
      correlation to function.
AB  - Stem bromelain is a proteolytic phytoprotein with a variety of therapeutic
      effects. Understanding its structural properties could provide insight into the
      mechanisms underlying its clinical utility. Stem bromelain was evaluated for its
      conformational and folding properties at the pH conditions it encounters when
      administered orally. It exists as a partially folded intermediate at pH 2.0. The
      conformational changes to this intermediate state were evaluated using
      fluorinated alcohols known to induce changes similar to those seen in vivo.
      Studies using circular dichroism, fluorescence emission spectroscopy, binding of
      the hydrophobic dye 1-anilino-8-naphthalene sulfonic acid and mass spectrometry
      indicate that treatment with 10-30% hexafluoroisopropanol induces the partially
      folded intermediate to adopt much of the native protein's secondary structure,
      but only a rudimentary tertiary structure, characteristic of the molten globule
      state. Addition of slightly higher concentrations of hexafluoroisopropanol caused
      transformation from an alpha-helix to a beta-sheet and induced formation of a
      compact nonnative structure. This nonnative form was more inhibitory of cell
      survival than either the native or the partially folded intermediate forms, as
      measured by enhanced suppression of proliferative cues (e.g., extracellular
      signal-regulated kinase) and initiation of apoptotic events. The nonnative form
      also showed better antitumorigenic properties, as evaluated using an induced two
      stage mouse skin papilloma model. In contrast, the nonnative state showed only a
      fraction of the proteolytic activity of the native form. This study demonstrates
      that hexafluoroisopropanol can induce a conformational change in stem bromelain
      to a form with potentially useful therapeutic properties different from those of
      the native protein.

PMID- 20156583
TI  - Micronucleus formation, DNA damage and repair in premenopausal women chronically
      exposed to high level of indoor air pollution from biomass fuel use in rural
      India.
AB  - Genotoxicity of indoor air pollution from biomass fuel use has been examined in
      132 biomass users (median age 34 years) and 85 age-matched control women from
      eastern India who used the cleaner fuel liquefied petroleum gas (LPG) to cook.
      Micronucleus (MN) frequency was evaluated in buccal (BEC) and airway epithelial
      cells (AEC); DNA damage was examined by comet assay in peripheral blood
      lymphocytes (PBL); and expressions of gamma-H2AX, Mre11 and Ku70 proteins were
      localized in AEC and PBL by immunocytochemistry. Reactive oxygen species (ROS)
      generation in leukocytes was measured by flow cytometry, and the levels of
      superoxide dismutase (SOD) and total antioxidant status (TAS) in blood were
      measured by spectrophotometry. Real-time aerosol monitor was used to measure
      particulate pollutants in indoor air. Compared with controls, biomass users had
      increased frequencies of micronucleated cells in BEC (3.5 vs. 1.7, p<0.001) and
      AEC (4.54 vs. 1.86, p<0.001), and greater comet tail % DNA (18.6 vs. 11.7%,
      p<0.01), tail length (45.5 vs. 31.4mum, p<0.01) and olive tail moment (4.0 vs.
      1.4, p<0.01) in PBL. Moreover, biomass users had more gamma-H2AX-positive nuclei
      in PBL (49.5 vs. 8.5%, p<0.01) and AEC (11.3 vs. 2.9%, p<0.01) along with higher
      expression of DNA repair proteins Mre11 and Ku70 in these cells, suggesting
      stimulation of DNA repair mechanism. Biomass users showed rise in ROS generation
      and depletion of SOD and TAS. Biomass-using households had 2-4 times more
      particulate matter with diameter less than 10 and 2.5mum in indoor air, and MN
      frequency and comet tail % DNA were positively associated with these pollutants
      after controlling potential confounders. Thus, chronic exposure to biomass smoke
      causes chromosomal and DNA damage and upregulation of DNA repair mechanism.

PMID- 20156584
TI  - Gangliosides influence EGFR/ErbB2 heterodimer stability but they do not modify
      EGF-dependent ErbB2 phosphorylation.
AB  - Gangliosides are well-known regulators of cell differentiation through specific
      interactions with growth factor receptors. Previously, our group provided the
      first evidence about stable association of ganglioside GM(3) to EGFR/ErbB2
      heterodimers in mammary epithelial cells. Goals of the present study were to
      better define the role of gangliosides in EGFR/ErbB2 heterodimerization and
      receptor phosphorylation events and to analyze their involvement in mammary cell
      differentiation. Experiments have been conducted using the ceramide analogue (+/
      )-treo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol hydrochloride ([D]-PDMP),
      which inhibits ceramide glucosyltransferase resulting in the endogenous
      ganglioside depletion, and the lactogenic hormone mix DIP (dexamethasone,
      insulin, prolactin), which induces cell differentiation and beta-casein mRNA
      synthesis. In addition, treatments of ganglioside-depleted cells with exogenous
      GM(3) have been carried out to ascertain the specific involvement of this
      ganglioside. Results from co-immunoprecipitation and Western blot experiments
      have shown that the endogenous ganglioside depletion resulted in the
      disappearance of SDS-stable EGFR/ErbB2 heterodimers and in the appearance of
      tyrosine-phosphorylated EGFR also in the absence of EGF stimulation; exogenous
      GM(3) added in combination with [D]-PDMP reversed both these effects. In
      contrast, the tyrosine phosphorylation of ErbB2 in ganglioside-depleted cells
      occurred only after EGF stimulation. Moreover, when ganglioside-depleted cells
      were treated with DIP in absence of EGF, beta-casein gene expression appeared
      strongly down-regulated, and beta-casein mRNA levels were partially restored by
      exogenous GM(3) treatment. Altogether, although the involvement of other
      ganglioside species cannot be excluded, these findings sustain the ganglioside
      GM(3) as an essential molecule for EGFR/ErbB2 heterodimer stability and important
      regulator of EGFR tyrosine phosphorylation, but it is not crucial for tyrosine
      phosphorylation of the heterodimerization partner ErbB2. Moreover, modulation of
      EGFR phosphorylation may explain how gangliosides contribute to regulate the
      lactogenic hormone-induced mammary cell differentiation.

PMID- 20156585
TI  - Endothelial damage and stem cell repair in atherosclerosis.
AB  - Atherosclerosis is a slowly progressing and multifactorial disease, in which
      endothelial dysfunction and damage play an initial role. Many risk factors for
      atherosclerosis can lead to endothelial damage of the vessel, especially in the
      areas where blood flow is disturbed. In the presence of hyperlipidemia, disturbed
      blood flow results in increased endothelial turnover in the arterial wall. It was
      demonstrated that disturbed blood flow activates endoplasmic reticulum stress
      initiating a signal pathway leading to endothelial apoptosis. Following
      endothelial death, the neighboring mature endothelial cells actively proliferate
      and migrate to heal the wound. However, stem cell repairing may be needed if
      endothelial damage is severe. As rapid development of stem cell research, it is
      expected that stem/progenitor cells may serve as a new source for vascular
      repair. In this review, we aim at examining key elements of endothelial turnover
      in atherosclerosis, i.e. damage and repair. We will also discuss the mechanisms
      of the process repaired by mature endothelial as well as stem cells, and
      highlight recent reciprocal stem cell application, which may provide a new hope
      to the treatment of severe atherosclerotic complications.

PMID- 20156586
TI  - Reduction of insulin resistance with effective clearance of hepatitis C
      infection: results from the HALT-C trial.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is associated with an
      increased prevalence of diabetes and insulin resistance (IR); whether this is a
      causal relationship has not been established. METHODS: We performed a
      longitudinal study within the lead-in phase of the Hepatitis C Antiviral Long
      Term Treatment against Cirrhosis (HALT-C) Trial to evaluate whether suppression
      of hepatitis C is associated with improvement in IR. Participants had advanced
      hepatic fibrosis and carried non-3 HCV genotypes (n = 96). Patients underwent 24
      weeks of pegylated interferon and ribavirin therapy and were categorized into HCV
      clearance groups at week 20 on the basis of HCV RNA levels; null responders had
      <1 log(10) decline (n = 38), partial responders had >or=1 log(10) decline (n =
      37) but detectable HCV RNA, and complete responders had no detectable HCV RNA (n
      = 21). The primary outcome was change (week 20 minus week 0) in IR by using the
      homeostasis model assessment (HOMA2-IR). RESULTS: Adjusting only for baseline
      HOMA2-IR, mean HOMA2-IR differences were -2.23 (complete responders), -0.90
      (partial responders), and +0.18 (null responders) (P = .036). The observed
      differences in mean HOMA2-IR scores were ordered in a linear fashion across
      response groups (P = .01). The association between HCV clearance and improvement
      in HOMA2-IR could not be accounted for by adiponectin or tumor necrosis factor
      alpha and was independent of potential confounders including age, gender,
      ethnicity, body mass index, duration of infection, medications used, and
      fibrosis. CONCLUSIONS: HCV suppression correlates with improvement in IR. These
      data provide further support for a role of HCV in the development of insulin
      resistance.

PMID- 20156587
TI  - Electronic images of the month. Use of computed tomography with reformatted
      imaging to identify ingested drug packets.

PMID- 20156588
TI  - Eosinophilic cholangitis.

PMID- 20156590
TI  - Molecular mechanisms of adrenergic stimulation in the heart.
AB  - Increased cardiac output in response to beta-adrenergic receptor stimulation is
      achieved by rapid alteration of the activity of cardiac ion channels, pumps, and
      exchangers. Over the past decade, the discovery of macromolecular complexes,
      which include the ion channels and pumps and the kinases that control their level
      of phosphorylation, has led to an increased understanding of the molecular
      mechanisms behind the cardiac adrenergic response. The increased understanding
      has led to the discovery of a new long QT gene encoding an accessory protein in
      one of these macromolecular complexes. This article briefly reviews the major
      components of the beta-adrenergic pathway in the heart and discusses the
      direction of current and future research.

PMID- 20156591
TI  - Noninvasive stereotactic radiosurgery (CyberHeart) for creation of ablation
      lesions in the atrium.
AB  - BACKGROUND: A variety of catheter-based energy modalities are used for cardiac
      ablation to treat arrhythmias. Robotic radiosurgery is increasingly being
      utilized to successfully accomplish precise tissue ablation in anatomically
      remote areas. OBJECTIVE: The purpose of this study was to examine the
      experimental feasibility of a noninvasive method using stereotactic robotic
      radiosurgery (SRS) to create cardiac lesions. METHODS: Sixteen (16) Hanford
      Sinclair mini swine (weight 40-70 kg) under general anesthesia were studied.
      Baseline computed tomographic scans were performed, followed by electroanatomic
      mapping using the CARTO system. Stereotactic robotic radiosurgery was performed
      using the CyberHeart system, with predetermined targets at the cavotricuspid
      isthmus, AV node, pulmonary vein-left atrial junction, or left atrial appendage.
      From 25 to 196 days after treatment, the animals were investigated with repeat
      electroanatomic voltage mapping and transesophageal echocardiography, when
      possible. The animals then were sacrificed and pathology specimens taken.
      RESULTS: Dose ranging suggested that 25 Gy was needed to produce an
      electrophysiologic effect. The time course showed an electrophysiologic effect
      consistently by 90 days. The method was feasible for producing bidirectional
      cavotricuspid isthmus block and AV nodal conduction block. The pulmonary vein
      left atrial junction and left atrial appendage showed marked voltage reduction to
      less than 0.05 mV. No spontaneous arrhythmias were observed. Pathology specimens
      showed no evidence of radiation damage outside the target. Histology samples from
      target sites showed effects consistent with X-beam radiation. CONCLUSION:
      Stereotactic robotic radiosurgery can produce cavotricuspid isthmus block, AV
      nodal block, and significant decreased voltage at the pulmonary vein-left atrial
      junction. No other organ damage was seen. The study findings demonstrate the
      feasibility of this noninvasive treatment method for creating cardiac lesions.
      This approach merits further investigation in the treatment of arrhythmias.

PMID- 20156592
TI  - Microvolt T-wave alternans and electrophysiologic testing predict distinct
      arrhythmia substrates: implications for identifying patients at risk for sudden
      cardiac death.
AB  - BACKGROUND: Better risk stratification of patients receiving an implantable
      cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death
      (SCD) is needed. Although microvolt T-wave alternans (MTWA) and
      electrophysiologic study (EPS) are independent markers for SCD, the Alternans
      Before Cardioverter Defibrillator (ABCD) trial found the combination to be more
      predictive than either test alone. OBJECTIVE: The purpose of this study was to
      test the hypothesis that EPS and MTWA measure different elements of the
      arrhythmogenic substrate and, therefore, predict distinct arrhythmia outcomes.
      METHODS: The ABCD trial enrolled 566 patients with ischemic cardiomyopathy, left
      ventricular ejection fraction (LVEF) <or=0.40, and nonsustained ventricular
      tachycardia. All patients underwent both MTWA test and EPS. The performance of
      MTWA and EPS in predicting stable ventricular tachyarrhythmic events (S-VTEs)
      versus unstable ventricular tachyarrhythmic events (U-VTEs), defined as either
      polymorphic ventricular tachycardia or ventricular fibrillation, was analyzed
      using Kaplan-Meier event rates and the log rank test. RESULTS: MTWA and EPS were
      abnormal in 71% and 39% of patients, respectively. There were 28 S-VTEs and 10 U
      VTEs. MTWA was predictive of U-VTEs (event rate 2.7% in abnormals vs 0% in
      normals, P = .04), whereas EPS was not (1.5% vs 3.2%, P = .55). In contrast, EPS
      predicted S-VTEs (9.7% vs 2.2%, P <.01), but MTWA did not (5.5% vs 4.4%, P =
      .57). Whereas the extent of left ventricular contractile dysfunction alone (LVEF
      <or=0.30 vs LVEF 0.31-0.40) did not predict events, MTWA predicted events better
      than did EPS in subjects with LVEF <or=0.30. In contrast, EPS predicted events
      better than did MTWA test in subjects with LVEF >0.30. CONCLUSION: The study data
      suggest that EPS and MTWA identify distinct arrhythmogenic substrates and, when
      used in combination, may better predict the complex electroanatomic substrates
      that underlie the risk for SCD.

PMID- 20156593
TI  - Functional anatomy of intrathoracic neurons innervating the atria and ventricles.

PMID- 20156594
TI  - To the Editor:--weakened ICD header bond.

PMID- 20156595
TI  - Atrioventricular nodal ablation predicts survival benefit in patients with atrial
      fibrillation receiving cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) benefits patients with
      advanced heart failure. The role of atrioventricular nodal (AVN) ablation in
      improving CRT outcomes, including survival benefit in CRT recipients with atrial
      fibrillation, is uncertain. OBJECTIVE: The purpose of this study was to assess
      the impact of AVN ablation on clinical and survival outcomes in a large atrial
      fibrillation and heart failure population that met the current indication for CRT
      and to determine whether AVN ablation is an independent predictor of survival in
      CRT recipients. METHODS: Of 154 patients with atrial fibrillation who received
      CRT-D, 45 (29%) underwent AVN ablation (+AVN-ABL group), whereas 109 (71%)
      received drug therapy for rate control during CRT (-AVN-ABL group). New York
      Heart Association (NYHA) class, electrocardiogram, and echocardiogram were
      assessed before and after CRT. Survival data were obtained from the national
      death and location database (Accurint). RESULTS: CRT comparably improved left
      ventricular ejection fraction (8.1% +/- 10.7% vs 6.8% +/- 9.6%, P = .49) and left
      ventricular end-diastolic diameter (-2.1 +/- 5.9 mm vs -2.1 +/- 6.7 mm, P = .74)
      in both +AVN-ABL and -AVN-ABL groups. Improvement in NYHA class was significantly
      greater in the +AVN-ABL group than in -AVN-ABL group (-0.7 +/- 0.8 vs -0.4 +/-
      0.8, P = .04). Survival estimates at 2 years were 96.0% (95% confidence interval
      [CI] 88.6%-100%) for +AVN-ABL group and 76.5% (95% CI 68.1%-85.8%) for-AVN-ABL
      group (P = .008). AVN ablation was independently associated with survival benefit
      from death (hazard ratio [HR] 0.13, 95% CI 0.03-0.58, P = .007) and from combined
      death, heart transplant, and left ventricular assist device (HR 0.19, 95% CI 0.06
      0.62, P = .006) after CRT. CONCLUSION: Among patients with atrial fibrillation
      and heart failure receiving CRT, AVN ablation for definitive biventricular pacing
      provides greater improvement in NYHA class and survival benefit. Larger-scale
      randomized trials are needed to assess the clinical and survival outcomes of this
      therapy.

PMID- 20156597
TI  - Using decision aids may improve informed consent for research.
AB  - This commentary argues that the existing approach towards obtaining informed
      consent for clinical research may be improved by using decision aids. Problems
      with the current approach include i) an emphasis on documentation to the
      detriment of good quality decision-making; ii) ad hoc rather than theory-based
      research studying how to improve informed consent; and iii) a lack of clarity
      around what is meant by 'comprehension' and how to measure it. Decision aids,
      which clearly improve patient treatment decisions but are new to decisions
      surrounding study participation, have strengths in precisely the areas where the
      informed consent literature is weak. Decision aids facilitate a process of
      decision-making, combining clear documentation, exercises to facilitate decision
      making, and consultation. They are increasingly informed by theory and clear,
      empirically-derived standards. Furthermore, decision aid research has clearly
      defined and operationalized three indicators of good quality decision-making in
      situations where there is no objectively correct answer: demonstrable knowledge
      of key aspects of the decision, accurate perceptions of the probabilities of
      various outcomes, and a match between preferred outcomes and the choice made. We
      identify outstanding issues and propose a research approach that will determine
      whether the use of decision aids can improve the informed consent process.

PMID- 20156596
TI  - Ion channel trafficking: a new therapeutic horizon for atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common cardiac arrhythmia with potentially life
      threatening complications. Drug therapies for treatment of AF that seek long-term
      maintenance of normal sinus rhythm remain elusive due in large part to
      proarrhythmic ventricular actions. Kv1.5, which underlies the atrial specific
      I(Kur) current, is a major focus of research efforts seeking new therapeutic
      strategies and targets. Recent work has shown a novel effect of antiarrhythmic
      drugs where compounds that block Kv1.5 channel current also can alter ion channel
      trafficking. This work further suggests that the pleiotropic effects of
      antiarrhythmic drugs may be separable. Although this finding highlights the
      therapeutic potential for selective manipulation of ion channel surface density,
      it also reveals an uncertainty regarding the specificity of modulating
      trafficking pathways without risk of off-target effects. Future studies may show
      that specific alteration of Kv1.5 trafficking can overcome the proarrhythmic
      limitations of current pharmacotherapy and provide an effective method for long
      term cardioversion in AF.

PMID- 20156598
TI  - The genetic structure of Neisseria meningitidis populations in Cuba before and
      after the introduction of a serogroup BC vaccine.
AB  - We investigated the population genetics in collections of meningococci sampled in
      Cuba during the period 1983-2005, thereby covering a period before and after the
      introduction of an antimeningococcal B-C vaccine. A total of 163 case isolates
      and 210 isolates from healthy carriers were characterized by multilocus sequence
      typing (MLST) and sequence determination of porA, porB and fetA genes. A total of
      56 sequence types (STs) including 28 new STs were identified among these
      isolates. The analysis of surface antigens revealed variants 3-1 and 3-8 to be
      prevalent for porB; variant F5-1 was the most common FetA epitope, and variants
      19 and 15 corresponded to the prevalent variable regions 1 (VR1) and VR2 PorA
      epitopes, respectively. The strongest associations between specific surface
      protein variants and clonal complexes were detected in lineages ST-32 and ST-53.
      All ST-32 complex isolates possessed porB3 alleles, and the most frequent antigen
      combination among ST-32 complex isolates was P1.19,15;F5-1. Variants PorB3-64 at
      PorB and P1.30 at PorA VR2, in combination with the PorA VR1 variants P1.12-1,
      P1.7 and P1.7-2 as well as the FetA variants F1-2 and F1-7, dominated the ST-53
      complex organisms. Furthermore, we observed a statistically significant
      association between the most frequent porA, porB and fetA alleles and strain
      invasiveness. Finally, this study showed that the application of VA-MENGOC
      BC((R)), the Cuban antimeningococcal vaccine, reduced the number and frequency of
      the hypervirulent Clonal Complexes ST-32 and ST-41/44, and also impacted on other
      lineages. The vaccine also affected the genetic composition of the carrier
      associated meningococcal isolates. The number of carrier isolates belonging to
      hypervirulent lineages decreased significantly after vaccination, and ST-53, a
      sequence type common in carriers, became the predominant ST.

PMID- 20156599
TI  - Phylogenetic, morphological and behavioural analyses support host switching of
      Trypanosoma (Herpetosoma) lewisi from domestic rats to primates.
AB  - We characterized four Brazilian trypanosomes isolated from domestic rats and
      three from captive non-human primates that were morphologically similar to T.
      lewisi, a considered non-pathogenic species restricted to rodents and transmitted
      by fleas, despite its potential pathogenicity for infants. These isolates were
      identified as T. lewisi by barcoding using V7V8 SSU rDNA sequences. In inferred
      phylogenetic trees, all isolates clustered tightly with reference T. lewisi and
      T. lewisi-like trypanosomes from Europe, Asia and Africa and despite their high
      sequence conservation formed a homogeneous clade separate from other species of
      the subgenus T. (Herpetosoma). With the aim of clearly resolving the
      relationships between the Brazilian isolates from domestic rats and primates, we
      compared sequences from more polymorphic ITS rDNA. Results corroborated that
      isolates from Brazilian rats and monkeys were indeed of the same species and
      quite close to T. lewisi isolates of humans and rats from different geographical
      regions. Morphology of the monkey isolates and their behaviour in culture and in
      experimentally infected rats were also compatible with T. lewisi. However,
      infection with T. lewisi is rare among monkeys. We have examined more than 200
      free-ranging and 160 captive monkeys and found only three infected individuals
      among the monkeys held in captivity. The findings of this work suggest that
      proximity of monkeys and infected rats and their exposure to infected fleas may
      be responsible for the host switching of T. lewisi from their natural rodent
      species to primates. This and previous studies reporting T. lewisi in humans
      suggest that this trypanosome can cause sporadic and opportunistic flea-borne
      infection in primates.

PMID- 20156600
TI  - Prevalence and phylogenetic analysis of rotavirus genotypes in Thailand between
      2007 and 2009.
AB  - Rotaviruses are the most common cause of severe diarrhea among infants and young
      children worldwide, especially in developing countries. In Thailand, rotavirus
      has presented a major public health problem causing severe diarrhea in infants
      and young children. It was responsible for about one-third of diarrheal diseases
      in hospitalized patients. In this study, we have analyzed the distribution and
      performed molecular characterization of rotaviruses circulating in infants and
      young children with diarrhea admitted to the city and rural hospitals in Thailand
      between July 2007 and May 2009. Group A human rotavirus was detected in 158
      (28.4%) of 557 fecal specimens by RT-PCR. The peak incidence of infection was
      found in the winter months between December and March. The G1P[8] strain was
      identified as the most prevalent (49.4%) followed by G9P[8] (22.2%), G2P[4]
      (20.2%) and G3P[8] (0.6%). The uncommon strains G12P[8], G12P[6] and G3P[9] were
      also detected. Phylogenetic analysis of selected G and P genotypes isolated in
      this study was performed to compare with the reference strains from different
      countries. Emergence of G12 in the northern part of Thailand was observed and
      phylogenetic analysis demonstrated close relation between Thai isolates and
      strains from India. The present study reveals the recurring changing genotypes of
      rotavirus circulating in Thailand. The genetic association between isolates from
      Thailand and other countries ought to be considered with regard to local and
      global dissemination of rotavirus as it is crucial for prevention especially,
      with respect to vaccine implementation.

PMID- 20156601
TI  - ERIC PCR and RAPD based fingerprinting of Salmonella Typhi strains isolated over
      a period of two decades.
AB  - Salmonella enterica serotype Typhi strains (n=113) were isolated from typhoid
      patients over a period of 2 decades, i.e. 1987-2006. RAPD and ERIC PCR methods
      were used for random whole genome typing of these strains. ERIC PCR was found to
      be very efficient with the discriminatory index (DI) of 0.9821 with 100%
      reproducibility. RAPD was satisfactory in discriminating the strains (DI=0.8978)
      but with poor reproducibility (40%). However, composite genotypic analysis was
      still better with DI of 0.9981 but with inherent poor reproducibility due to
      RAPD. Two major clones were observed to be circulating in the community with few
      unrelated strains too. The dendrogram constructed based on ERIC PCR banding
      pattern by involving 89 Typhi strains revealed 71 patterns, indicating that the
      genome of the bacterium is capable of rapid changes and variations. Thus, the
      spectrum of biological manifestations of human infection by S. Typhi may be
      related to its capacity for genetic diversity underlined by its highly plastic
      hypermutable genome.

PMID- 20156602
TI  - A novel cyclin-dependent kinase inhibitor down-regulates tumor necrosis factor
      alpha (TNF-alpha)-induced expression of cell adhesion molecules by inhibition of
      NF-kappaB activation in human pulmonary epithelial cells.
AB  - BAI (a novel cyclin-dependent kinase (CDK) inhibitor, 2-[1,1'-biphenyl]-4-yl-N-[5
      (1,1-dioxo-1lambda(6)-isothiazolidin-2-yl)-1H-indazol-3-yl] acetamide) is known
      to have anti-proliferative activity, but the mechanism responsible for it remains
      unclear. We here investigated the functional effect of BAI on airway inflammation
      and its action mechanism. BAI down-regulated the expression of intercellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in
      human lung epithelial A549 cells stimulated with tumor necrosis factor-alpha:
      (TNF-alpha), resulting in the suppression of leukocyte adhesion to lung
      epithelial A549 cells. In addition, BAI inhibited TNF-alpha-induced expression of
      adhesion molecules (ICAM-1 and VCAM-1) protein and mRNA in a dose-dependent
      manner. BAI inhibited nuclear factor-kappaB (NF-kappaB) activity and nuclear
      translocation of NF-kappaB. Furthermore, BAI potently inhibits the TNF-alpha
      induced increase in ROS generation in A549 cells, suggesting that inhibition of
      ROS generation is maybe involved in the BAI-mediated inhibition of TNF-alpha
      induced ICAM-1 down-regulation to A549 cells. Taken together, these results
      suggest that BAI inhibits cell adhesion through inhibition of ICAM-1 and VCAM-1
      expressions, at least in part, by inhibition of ROS generation and down
      regulation of NF-kappaB activity.

PMID- 20156603
TI  - Wegener's Granulomatosis vasculitis and granuloma.
AB  - Wegener's Granulomatosis (WG) is an autoimmune disease with manifestations in
      different organ systems. The hallmark of WG is a necrotizing granulomatous
      inflammation of the upper and/or lower respiratory tract and systemic small
      vessel vasculitis which can involve multiple organ systems. The treatment of WG
      has evolved over the last decades. Steroid, cytotoxic and biologic therapies have
      been used leading to great improvements in outcome. However, still mortality is
      high and relapses are a major cause of mortality and morbidity. Despite
      intensified maintenance regimens and new possibilities of biologic therapies in
      WG the relapse rate is high. Even patients treated with high dose cytotoxic
      therapies in autologous stem cell treatment protocols have shown relapses in the
      course of disease. Increasing knowledge of the pathophysiology of granuloma in WG
      and new biologic therapies might be of great importance for future treatment of
      WG.

PMID- 20156604
TI  - Effect of respiratory muscle training on maximum aerobic power in normoxia and
      hypoxia.
AB  - To assess the effects of respiratory muscle training (RMT) on maximum oxygen
      uptake (VO2max) in normoxia and hypoxia, 9 healthy males (age 24 +/- 4 years;
      stature 1.75 +/- 0.08 m; body mass 72 +/- 9 kg; mean +/- SD) performed on
      different days maximal incremental tests on a cycle ergometer in normoxia and
      normobaric hypoxia (FIO2=0.11), before and after 8 weeks of RMT (5 days/week).
      During each test, gas exchange variables were measured breath-by-breath by a
      metabolimeter. After RMT, no changes in cardiorespiratory and metabolic variables
      were detected at maximal exercise in normoxia. On the contrary, in hypoxia
      expired and alveolar ventilation (V(E(and V(A), respectively) at maximal exercise
      were significantly higher than pre-training condition (+12 and +13%,
      respectively; P < 0.05). Accordingly, alveolar O2 partial pressure (PAO2) after
      RMT significantly increased by approximately 10%. Nevertheless, arterial PO2 and
      VO2max did not change with respect to pre-training condition. In conclusion, RMT
      improved respiratory function but did not have any effect on VO2max, neither
      under normoxic nor hypoxic condition. In hypoxia, the significant increase in
      V(E) and V(A) at maximum exercise after training lead to higher alveolar but not
      arterial PO2 values, revealing an increased A-a gradient. This result, according
      to the theoretical models of VO2max limitation, seems to contradict the lack of
      VO2max increase in hypoxia, suggesting a possible role of increased ventilation
      perfusion mismatch.

PMID- 20156605
TI  - Subcutaneous internal lateral sphincterotomy (SILS) versus nitroglycerine
      ointment in anal fissure: a prospective study.
AB  - AIM: To compare the results of subcutaneous internal lateral sphincterotomy under
      local anesthesia and nitroglycerin ointment treatments in acute and chronic anal
      fissures. METHODS: This was a comparative, prospective study of 340 patients of
      acute and chronic anal fissure. The patients voluntarily opted either for the
      surgical procedure under local anesthesia, or the nitroglycerin treatment. All
      the patients were followed with regular checkups and complaints were documented.
      RESULTS: Except for 1.75% patients having bleeding/hematoma formation, and with a
      dropout of 2.60% patients, no failure, recurrence or long term complications like
      incontinence, were observed in patients who underwent subcutaneous internal
      lateral sphincterotomy after a mean follow up of 28 months. With surgical
      treatment pain, bleeding per rectum and constipation showed significant
      improvement as compared to nitroglycerin treatment. Fissure healing was 100% in
      surgical group as compared to 56.90% in medical group (P=0.000, odds
      ratio=344.6). Nitroglycerin was equally effective in acute and chronic fissures
      (P=0.096). CONCLUSION: Subcutaneous internal lateral sphincterotomy under local
      anesthesia is more curative, easy and safe, in the hands of a beginner as well as
      an experienced surgeon, with highest patient satisfaction, and should be
      considered as the first line of therapy in both chronic and resistant/recurrent
      acute anal fissures.

PMID- 20156606
TI  - Ten-year probability of osteoporotic fracture in 2012 Polish women assessed by
      FRAX and nomogram by Nguyen et al.-Conformity between methods and their clinical
      utility.
AB  - PURPOSE: The aim of the cross-sectional study was to establish the degree of
      conformity between 10-year probability of osteoporotic fracture, assessed by
      FRAX, and using the nomograms, as proposed by Nguyen at al. METHODS:
      Postmenopausal Polish women (2012) were examined in their mean age of 68.5+/-7.9
      years (age range 55-90 years). Fracture probability by FRAX was based on age,
      BMI, prior fracture, hip fracture in parents, steroid use, rheumatoid arthritis,
      alcohol use, secondary osteoporosis and T-score for femoral neck BMD. Fracture
      probability by Nguyen's nomograms was based on age, the number of prior
      fractures, the number of falls and T-score for femoral neck BMD. RESULTS: The
      mean conformity rate was 79.1% for any fracture risk (for threshold 20%) and
      79.5% for hip fracture (threshold 3%). Any and hip fracture risks were
      significantly higher for both methods in women with fracture history in
      comparison to those without fracture and increased with ageing. The influence of
      prior fracture and ageing was more evident in Nguyen's nomograms. ROC analyses of
      any fracture risk in FRAX and Nguyen's methods demonstrated the area under curve
      (AUC) at 0.833 and 0.879, respectively. Similar analyses for hip fracture
      demonstrated AUCs for FRAX and Nguyen's technique at 0.726 and 0.850,
      respectively. The AUCs for Nguyen's nomograms were significantly larger than the
      AUCs for FRAX (p<0.0001). CONCLUSION: The mean conformity for any fracture risk
      is 79.1% and 79.5% for hip fracture. Nguyen's nomograms seem to be more efficient
      in fracture risk assessment, especially for hip fractures, due to a higher
      accuracy of the method. The information on the number of falls during the last
      year and multiple fractures ought to be incorporated into the method of fracture
      risk prediction. MINI-ABSTRACT: The degree of conformity was assessed in a group
      of 2012 women between 10-year FRAX prognosis of fracture and Nguyen et al.'s
      nomograms. The mean conformity for any fracture risk is 79.1% and 79.5% for hip
      fracture. Nguyen's nomograms seem to be more efficient in fracture risk
      assessment due to higher accuracy.

PMID- 20156607
TI  - Dormant pulmonary vein conduction unmasked by external electrical cardioversion.

PMID- 20156608
TI  - Management of recurrent atrial arrhythmias after minimally invasive surgical
      pulmonary vein isolation and ganglionic plexi ablation for atrial fibrillation.
AB  - BACKGROUND: Minimally invasive thoracoscopic procedures have evolved for surgical
      treatment of atrial fibrillation (AF). The spectrum and management of arrhythmias
      after minimally invasive epicardial radiofrequency ablation of the pulmonary vein
      (PV) antrum have not been well studied. OBJECTIVE: The aim of this study was to
      describe the spectrum and treatment of recurrent atrial tachyarrhythmias (AT)
      after minimally invasive AF surgery. METHODS: Fifty patients underwent bipolar
      radiofrequency (RF) ablation of the PV antrum, parasympathetic ganglionated
      plexi, and ligament of Marshall. Twenty patients (40%) had recurrent AT, and 13
      underwent electrophysiology study 100 to 948 days postoperatively (mean 383 +/-
      234). RESULTS: Fourteen arrhythmias were identified in 13 patients 90 to 666 days
      (mean 214 +/- 162) after AF surgery. The most common arrhythmias were AF (N = 8)
      and atrial flutter (N = 3). Of 44 PVs examined, 22 (50%) had reconnected. Seven
      of 8 patients with recurrent AF had either 2 or 3 veins reconnected, and 6 of 8
      had reconnection of the left superior PV. On average, 25.6% of each PV
      reconnected and showed conduction delay between the left atrium and PV. Two of 4
      postoperative atrial flutters were due to isthmus-dependent re-entry. After
      catheter ablation, 2 patients had symptomatic recurrence of AT. CONCLUSION:
      Recurrent AT occurs in up to 40% of patients after minimally invasive
      thoracoscopic AF surgery during a minimal follow-up of 12 months. PV reconnection
      accounts for most recurrences. Postoperative AT appears amenable to catheter
      ablation, often in conjunction with medical therapy, with high intermediate-term
      success.

PMID- 20156609
TI  - Successful integration of a computed tomography-based left atrial three
      dimensional model in an electroanatomically reconstructed right atrium for
      ablation of biatrial tachycardia.

PMID- 20156611
TI  - A paradigm shift for the heart's pacemaker.

PMID- 20156610
TI  - n-3 Polyunsaturated fatty acids alter expression of fibrotic and hypertrophic
      genes in a dog model of atrial cardiomyopathy.
AB  - BACKGROUND: We previously showed that omega-3 polyunsaturated fatty acids (PUFAs)
      reduce vulnerability to atrial fibrillation (AF). The mechanisms underlying this
      effect are unknown. OBJECTIVE: The purpose of this study was to use a genome-wide
      approach to identify gene expression profiles involved in a new model of AF
      vulnerability and to determine whether they were altered by PUFA therapy.
      METHODS: Thirty-six dogs were randomized evenly into three groups. Two groups
      were paced using simultaneous atrioventricular pacing (SAVP) at 220 bpm for 14
      days to induce atrial enlargement, fibrosis, and susceptibility to AF. One group
      was supplemented with oral PUFAs (850 mg/day) for 21 days, commencing 7 days
      before the start of pacing (SAVP-PUFAs). The second group received no PUFAs (SAVP
      No PUFAs). The remaining dogs were unpaced, unsupplemented controls (CTRL).
      Atrial tissue was sampled at the end of the protocol. Gene expression was
      analyzed in four dogs randomly selected from each group (n = 12) via microarray.
      Results were confirmed with quantitative real-time polymerase chain reaction (RT
      PCR) and histology on all 36 dogs. RESULTS: Microarray or quantitative RT-PCR
      results showed that SAVP-No PUFAs dogs had significantly increased mRNA levels of
      protein kinase B (Akt), epidermal growth factor (EGF), JAM3, myosin heavy chain
      alpha (MHCalpha), and CD99 and significantly decreased levels of Smad6 compared
      with CTRL dogs. Quantitative RT-PCR showed that PUFA supplementation was
      associated with significant down-regulation of Akt, EGF, JAM3, MHCalpha, and CD99
      levels compared with SAVP-No PUFAs dogs. CONCLUSION: The effect of PUFAs on these
      fibrosis, hypertrophy, and inflammation related genes suggests that, in this
      model, PUFA-mediated prevention of AF may be due to attenuation of adverse
      remodeling at the genetic level in response to mechanical stress.

PMID- 20156612
TI  - Pressure frequency characteristics of the pericardial space and thorax during
      subxiphoid access for epicardial ventricular tachycardia ablation.
AB  - BACKGROUND: Nonsurgical subxiphoid pericardial access may be useful in
      ventricular tachycardia ablation and other electrophysiologic procedures but has
      a risk of right ventricular puncture. OBJECTIVE: The purpose of this study was to
      identify a signature pressure frequency that would help identify the pericardial
      space and guide access. METHODS: The study consisted of 20 patients (8 women and
      12 men; mean age 59.1 +/- 14.2 years; left ventricular ejection fraction 25.2% +/
      12.2%; failed 1.8 +/- 0.5 endocardial ablations; unresponsive to 2.0 +/- 1.0
      antiarrhythmic drugs; 6 ischemic cardiomyopathy, 12 nonischemic cardiomyopathy, 2
      normal heart; 4 previous sternotomy) undergoing epicardial ventricular
      tachycardia ablation. After pericardial access was obtained, a 10Fr long sheath
      was used to record pressure inside the pericardium and pleural space. Pressures
      were analyzed using a fast Fourier transform to identify dominant frequencies in
      each chamber. RESULTS: Mean pressures in the pleural space and the pericardium
      were not different (7.7 +/- 1.9 mmHg vs 7.8 +/- 0.9 mmHg, respectively). However,
      the pericardial space in each patient demonstrated two frequency peaks that
      correlated with heart rate (1.16 +/- 0.21 Hz) and respiratory rate (0.20 +/- 0.01
      Hz), whereas the pleural space in each patient had a single peak correlating with
      respiratory rate (0.20 +/- 0.01 Hz). CONCLUSION: The pericardial space
      demonstrates a signature pressure frequency that is significantly different from
      the surrounding space. This difference may make minimally invasive subxiphoid
      pericardial access safer for nonsurgeons and may have important implications for
      electrophysiologic procedures.

PMID- 20156613
TI  - Mapping of dominant frequency and complex fractionated electrograms in atrial
      fibrillation patients: Caveat medicus.

PMID- 20156614
TI  - The temporal variability of dominant frequency and complex fractionated atrial
      electrograms constrains the validity of sequential mapping in human atrial
      fibrillation.
AB  - BACKGROUND: It has been proposed that sequential mapping of dominant frequency
      (DF) and complex fractionated atrial electrograms (CFAE) can identify target
      sites for ablation of atrial fibrillation (AF). These mapping strategies are
      valid only if DF and CFAE are temporally stable on the timescale of the mapping
      procedure. We postulate that DF and CFAE are temporally variable; consequently,
      sequential mapping can be misleading. OBJECTIVE: To make prolonged spatially
      stable multielectrode recordings to assess the temporal stability of DF and CFAE.
      METHODS: We recorded electrical activity for 5 minutes with the use of a 64
      electrode basket catheter placed in the left atrium of 18 patients presenting for
      AF ablation. DF and CFAE were determined off-line, and their temporal variability
      was quantified. Maps created from simultaneous versus sequentially acquired data
      were compared. RESULTS: DF was temporally variable: the average temporal
      coefficient of variation was 22.7% +/- 5.4%. DF sites were transient, meeting
      criteria for only 22.1 seconds out of 5 minutes. Similarly, CFAEs were transient
      (average duration of CFAE 8.8 +/- 11.3 seconds). DF and CFAE sequential maps
      failed to identify 93.0% +/- 12.4% and 35.9% +/- 14.9% of DF and CFAE sites,
      respectively. CONCLUSION: Because of temporal variability, sequential DF and CFAE
      maps do not accurately reflect the spatial distribution of excitation frequency
      during any given sampling interval. The spatial distribution of DF and CFAE sites
      on maps created with sequential point acquisition depends upon the time at which
      each site is sampled.

PMID- 20156615
TI  - Surgically placed left ventricular leads provide similar outcomes to percutaneous
      leads in patients with failed coronary sinus lead placement.
AB  - BACKGROUND: Cardiac resynchronization therapy using a left ventricular (LV) lead
      inserted via the coronary sinus (CS) improves symptoms of congestive heart
      failure, decreases hospitalizations, and improves survival. An epicardial LV lead
      is often placed surgically after a failed percutaneous attempt, but whether it
      offers the same benefits is unknown. OBJECTIVE: The purpose of this study was to
      determine if patients who receive a surgical LV lead after failed CS lead
      placement for cardiac resynchronization therapy derive the same benefit as do
      patients with a successfully placed CS lead. METHODS: A total of 452 patients
      underwent attempted CS lead insertion. Forty-five patients who had failed CS lead
      placement and then had surgical LV lead placement were matched with 135 patients
      who had successful CS lead placement. RESULTS: No major differences in
      preoperative variables were seen between groups. Postprocedural complications of
      acute renal injury (26.2% vs 4.9%, P <.001) and infection (11.9% vs 2.4%, P =
      .03) were more common in the surgical group. Mean long-term follow-up was 32.4 +/
      17.5 months for surgical patients and 39.4 +/- 14.8 months for percutaneous
      patients. At follow-up, all-cause mortality (30.6% vs 23.8%, P = .22) and
      readmission for congestive heart failure (26.2% vs 31.5%, P = .53) were similar
      between surgical and percutaneous groups. Improvement in New York Heart
      Association functional class (60.1% vs 49.6%, P = .17) was similar between
      surgical and percutaneous groups. CONCLUSION: Surgical LV lead placement offers
      functional benefits similar to those of percutaneous placement but with greater
      risk of perioperative complications, including acute renal failure and infection.

PMID- 20156616
TI  - Chronic performance of an active fixation coronary sinus lead.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and
      mortality in appropriately selected patients with heart failure. Optimal left
      ventricular (LV) lead placement is useful in enhancing response from CRT. Three
      significant obstacles to LV lead placement are patient-specific variations in
      coronary venous anatomy, phrenic nerve stimulation, and a significant rate of LV
      lead dislodgement or microdislodgement. OBJECTIVE: The primary objective of this
      study was to determine the safety and effectiveness of the Medtronic StarFix
      active fixation LV lead. Secondary objectives evaluated implant success, lead
      placement and procedure time, lead handling and lobe deployment, additional
      electrical performance, and all adverse events reported in the study. METHODS:
      There were 441 patients enrolled in this multicenter study. Standard cardiac
      resynchronization therapy (CRT) inclusion criteria were used. Patients were
      followed up for a mean of 23 months. Implant data, success with CRT, LV lead
      performance, clinical outcomes, and experience with LV lead revisions were
      prospectively evaluated. RESULTS: The mean LV stimulation threshold at implant
      was 1.3 +/- 1 volts and was stable over time. Sensing was also excellent. In
      96.3% of the implantations in this study, the physician was able to place the
      lead in a nonanterior position. Extracardiac (phrenic nerve) stimulation required
      invasive intervention in 11 subjects (2.5%). Only 3 dislodgements (0.7%) were
      observed. Two occurred in the first 5 implants and were attributed to inadequate
      engagement of the venous subbranch. CONCLUSION: The Medtronic 4195 is safe and
      highly efficacious. It affords the physician more choices in lead placement
      location and has a remarkably low dislodgement rate.

PMID- 20156617
TI  - Pathologic examination after epicardial ablation of ventricular tachycardia in
      cardiac sarcoidosis.

PMID- 20156618
TI  - Combined assessment of left ventricular dyssynchrony and contractility by
      speckled tracking strain imaging: a novel index for predicting responders to
      cardiac resynchronization therapy.
AB  - BACKGROUND: Mechanical dyssynchrony is an important factor in the response to
      cardiac resynchronization therapy (CRT). However, no echocardiographic measure
      can improve prediction of case selection for CRT. OBJECTIVE: The purpose of this
      study was to assess the efficacy of a newly combined echocardiographic index for
      ventricular dyssynchrony and contractility using speckled tracking strain
      analysis to predict responders to CRT. METHODS: Forty-seven patients with severe
      heart failure in New York Heart Association functional class III/IV, left
      ventricular ejection fraction </=35%, and QRS duration >/=130 ms were included in
      the study. Echocardiography was performed, and a novel index (i-Index), the
      product of radial dyssynchrony and radial strain, was calculated. Responder to
      CRT was defined as a patient with a >/=15% decrease in left ventricular end
      systolic volume at 6-month follow-up. RESULTS: Thirty-two patients (68%) were
      classified as responders. The i-Index was significantly higher in responders than
      in nonresponders (3,450 +/- 1180 vs 1,481 +/- 841, P <.001). The area under
      receiver operator characteristic curve was 0.92 for the i-Index, which was better
      than the index of radial dyssynchrony only (0.74). A cutoff value of i-Index
      >2,000 predicted responders with 94% sensitivity and 80% specificity. The index
      using only radial dyssynchrony had 81% sensitivity and 53% specificity.
      Furthermore, i-Index decreased in responders (1,985 +/- 1261, P <.001) but not in
      nonresponders (1,684 +/- 866, P = .48). CONCLUSION: Our findings suggest that a
      novel combined index by radial strain echocardiography might be a predictor of
      response to CRT. The value of this novel echocardiographic index requires further
      assessment in larger studies.

PMID- 20156619
TI  - Response interference between functional and structural actions linked to the
      same familiar object.
AB  - Viewing objects with the intention to act upon them may activate task-irrelevant
      motor responses. Many manufactured objects are associated with two action
      classes: grasping in accordance with object structure and skillful use consistent
      with object function. We studied the potential for within-object competition
      during action selection by comparing initiation latencies for "conflict" objects
      (with competing structure and function responses) to "non-conflict" objects (with
      a single response). We demonstrated a novel pattern of within-object interference
      wherein actions involving conflict objects were slowed when participants
      skillfully used those objects (grasp-on-use interference) as well as a second
      pattern of interference when conflict objects were grasped after skillfully using
      the same objects in previous blocks (long-term use-on-grasp interference). These
      data suggest that actions to common objects are influenced by competition between
      rapid but briefly maintained grasp responses and slower but longer-lasting use
      responses, and advance our understanding of the process and neural substrates of
      selection for action.

PMID- 20156620
TI  - Testing an associative account of semantic satiation.
AB  - How is the meaning of a word retrieved without interference from recently viewed
      words? The ROUSE theory of priming assumes a discounting process to reduce source
      confusion between subsequently presented words. As applied to semantic satiation,
      this theory predicted a loss of association between the lexical item and meaning.
      Four experiments tested this explanation in a speeded category-matching task. All
      experiments used lists of 20 trials that presented a cue word for 1s followed by
      a target word. Randomly mixed across the list, 10 trials used cues drawn from the
      same category whereas the other 10 trials used cues from 10 other categories. In
      Experiments 1a and 1b, the cues were repeated category labels (FRUIT-APPLE) and
      responses gradually slowed for the repeated category. In Experiment 2, the cues
      were nonrepeated exemplars (PEAR-APPLE) and responses remained faster for the
      repeated category. In Experiment 3, the cues were repeated exemplars in a word
      matching task (APPLE-APPLE) and responses again remained faster for the repeated
      category.

PMID- 20156621
TI  - Left gastric pseudoaneurysmal hemorrhage: a rare endoscopic detection.

PMID- 20156622
TI  - A large single-center experience of EUS-guided FNA of the left and right adrenal
      glands: diagnostic utility and impact on patient management.
AB  - BACKGROUND: EUS-guided FNA of the left and right adrenals has been described, but
      data are very limited. OBJECTIVES: Our primary objective was to determine the
      impact of the diagnostic utility of EUS-guided FNA of adrenal glands on patient
      management. Our secondary objective was to determine predictors of malignant
      adrenal involvement. STUDY DESIGN: Observational study. SETTING: Tertiary
      referral center. PATIENTS: Patients with enlarged adrenal(s) on abdominal imaging
      underwent EUS-guided FNA. The left adrenal (n = 54) was sampled via the
      transgastric approach and the right adrenal (n = 5) via a transduodenal approach.
      RESULTS: Fifty-nine patients (63% men, median age 65 years) were evaluated. The
      median adrenal gland size was 25 x 17 mm. Adrenal tissue adequate for
      interpretation was obtained in all of the patients. EUS-guided FNA confirmed
      malignancy in 22 (37%) patients. Based on size (> or =30 mm) alone, EUS had an
      accuracy of 68%. Patients with malignant cytology had higher standard uptake
      value scores on positron-emission tomography compared with patients with benign
      adrenal masses (P < .001). Malignant masses were more likely to have an altered
      adrenal gland shape compared with benign masses (crude odds ratio [OR] 12.0; P <
      .001). On multivariable analysis, altered adrenal gland shape was a significant
      predictor of malignancy (adjusted OR 7.94; P = .015), whereas a size of 30 mm or
      larger (adjusted OR 1.30; P = .774) and hypoechoic nature (adjusted OR 12.05; P =
      .148) were not. All patients except 2 with malignant cytology were treated with
      systemic therapy without the need for additional invasive biopsies or surgery. No
      immediate complications were encountered. LIMITATIONS: Lack of surgical criterion
      standard; 1 experienced endosonographer. CONCLUSIONS: EUS-guided FNA of the
      adrenal glands is a minimally invasive and safe approach that documents or
      excludes malignant involvement. EUS-guided FNA should be the first next test to
      evaluate enlarged adrenal glands because it directs therapy and affects patient
      management.

PMID- 20156623
TI  - Water sorption on coals.
AB  - Water vapor adsorption/desorption isotherm studies were performed on high
      volatile bituminous B coal and lignite to investigate the behavior of water on
      coal. The characterization of water sorption was studied by kinetic and
      equilibrium data, at a temperature of 298 K and a relative vapor pressure up to
      0.95. Water sorption isotherms have a standard type II sigmoid shape obeying the
      BET model in the relative pressure range 0.05-0.35. A modified BET model was used
      to estimate the water adsorbed on primary and secondary sites, respectively. The
      specific surface areas estimated with water and CO(2) were similar and about 95
      and 52 m(2) g(-1) for high volatile bituminous B coal and lignite, respectively.
      The adsorption capacity of water and CO(2) was related to the oxygen content of
      coal and the proportion of inorganic matter. The water adsorption and desorption
      isotherms produce a different hysteresis loop for the two coals. On the other
      hand, the diffusion coefficient of water adsorption was estimated at about 10(
      16) m(2) s(-1), by the unipore model. From the diffusion coefficient of water,
      which varied with increase in relative pressure, it is shown that water adsorbs
      first on primary sites, before formation of water clusters and their micropore
      filling which was a slow process.

PMID- 20156624
TI  - Highly luminescent quantum dots functionalized and their conjugation with IgG.
AB  - A sol-gel approach including partially removing capping agents, depositing SiO(2)
      monomers, and growing a SiO(2) shell was developed to generate a bio-compatible
      functionalization on CdTe quantum dots (QDs). The QDs retained their high
      photoluminescence (PL) efficiency after coating with a SiO(2) shell (22.5%) by
      controlling the surface state of the QDs to decrease PL degradation during a sol
      gel preparation. Furthermore, the CdTe QDs with a SiO(2) shell were conjugated
      with IgG using 3-sulfo-N-hydroxysuccinimide or streptavidin-maleimide as linkers.
      The biotin-streptavidin linker resulted in a high PL efficiency retained (only
      ~23% lower than the initial value of the QDs), which is crucial for bio
      applications.

PMID- 20156625
TI  - Mechanism of PEO-PPO-PEO micellization in aqueous solutions studied by two
      dimensional correlation FTIR spectroscopy.
AB  - The micellization mechanism of PEO-PPO-PEO block copolymer in aqueous solutions
      was studied by two-dimensional correlation FTIR spectroscopy. The 1400-1000 cm(
      1) region was investigated, involving the stretching vibrations of ether band, C
      H wagging vibrations of EO methylene groups and C-H symmetric deformation
      vibrations of PO methyl groups. In the 2D correlated spectra, the hydrous and
      anhydrous state of the ether band, PO methyl groups, and the two conformations of
      EO methylene groups were observed. Molecules with different PO lengths and
      increasing molecular weight were investigated to determine the sequence of
      association of the separate groups. During temperature-induced micellization, the
      following changes were detected: firstly, EO methylene groups changed from a
      gauche state to a trans state; secondly, conformational transitions led to the
      dehydration of hydrated methyl groups; next, the hydrogen bonding between C-O
      band and water diminished; and finally, dehydrated groups approached to form
      hydrophobic cores, resulting in micelle formation. From this variation in the
      sequence of group associations, it is concluded that aggregates of unimers first
      formed, then hydrophobic cores formed through the hydrophobic interaction from
      dehydrated PPO blocks, and proper micelles eventually evolved. The temperature
      induced conformational changes are suggested the reason for micellization.

PMID- 20156626
TI  - Digital necrobacillosis in Norwegian wild tundra reindeer (Rangifer tarandus
      tarandus).
AB  - Outbreaks of digital necrobacillosis in Norwegian wild tundra reindeer (Rangifer
      tarandus tarandus) are described. The outbreaks occurred in late summer and
      autumn 2007 and 2008, subsequent to periods with an unusually high number of days
      with precipitation and high air temperature. Lesions were generally restricted to
      one foot and the disease incidence was highest in calves. Single limbs from 20
      animals and six whole carcasses were submitted for laboratory examination. Gross
      lesions were characterized by swelling of the fetlock to coronary band area and
      cutaneous sinus tracts with sparse discharge of pus. Subcutaneous tissue was
      inflamed and oedematous with focal necrosis. Tendons, tendon sheaths, joints and
      periosteum of the digital bones were often affected. Animals shot during winter
      showed severe chronic periostitis and osteomyelitis and necrotizing deforming
      arthritis. Microscopically, skin lesions were characterized by deep ulcers with
      centrally located necrotic tissue, bordered by a zone of oedema and intense
      inflammation with granulation tissue and fibrosis. Necrosis, suppurative
      inflammation and oedema were found in the synovial membranes, tendons and tendon
      sheaths. Digital bone lesions were characterized by necrosis, fibrosis and
      extensive bone proliferation. Vasculitis and thrombosis were common in all
      lesions. Elongate filamentous gram-negative bacteria in necrotic lesions from all
      animals were identified as Fusobacterium necrophorum by fluorescence in-situ
      hybridization. F. necrophorum was cultured from the foot lesions of six animals.
      Five of these isolates were examined by 16S rRNA sequencing. The sequences were
      identical and differed from all other strains listed in GenBank. These results
      are consistent with circulation of a reindeer-adapted pathogenic strain of F.
      necrophorum in the wild reindeer population, causing outbreaks of digital
      necrobacillosis following warm and humid summers.

PMID- 20156627
TI  - Immunohistochemical detection of bluetongue virus in fixed tissue.
AB  - The VP7 structural protein is the most abundant of the major core proteins and is
      highly conserved in all serotypes of bluetongue virus (BTV). The aim of this
      study was to develop immunohistochemical techniques for the detection of BTV VP7
      in Bouin's- and formalin-fixed and paraffin wax-embedded tissues from small
      ruminants (sheep and goats) naturally infected with BTV. Tissue samples were
      taken from animals in which BTV infection had been confirmed by reverse
      transcriptase polymerase chain reaction. Optimal results were obtained by
      incubation of monoclonal antibody 2E9 on samples fixed with Bouin's solution or
      neutral buffered formalin. Optimum antigen retrieval for Bouin's-fixed samples
      was by microwave heating (6 min) of tissue samples in citrate buffer (pH 6.0,
      0.01 M), while for formalin-fixed samples a 30 min heating period in pH 9.0
      buffer was required. In both species, BTV was mainly detected in the spleen,
      lymph nodes and lungs; specifically within the arteriolar and capillary
      endothelial cells, together with macrophages and lymphocytes. The
      immunohistochemical method described will be a useful tool for future research.

PMID- 20156628
TI  - Identification of coastal water quality by statistical analysis methods in Daya
      Bay, South China Sea.
AB  - In this paper, cluster analysis (CA), principal component analysis (PCA) and the
      fuzzy logic approach were employed to evaluate the trophic status of water
      quality for 12 monitoring stations in Daya Bay in 2003. CA grouped the four
      seasons into four groups (winter, spring, summer and autumn) and the sampling
      sites into two groups (cluster DA: S1, S2, S4-S7, S9 and S12 and cluster DB: S3,
      S8, S10 and S11). PCA identified the temporal and spatial characteristics of
      trophic status in Daya Bay. Cluster DB, with higher concentrations of TP and DIN,
      is located in the western and northern parts of Daya Bay. Cluster DA, with the
      low Secchi, is located in the southern and eastern parts of Daya Bay. The fuzzy
      logic approach revealed more information about the temporal and spatial patterns
      of the trophic status of water quality. Chlorophyll a, TP and Secchi may be major
      factors for deteriorating water quality.

PMID- 20156629
TI  - Unusual stilbenoids and a stilbenolignan from seeds of Syagrus romanzoffiana.
AB  - Stilbenoids, syagrusins A-B (1-2), and a stilbenolignan, 5-hydroxyaiphanol (3),
      along with three known phenylpropanoids (4-6), were isolated from seeds of
      Syagrus romanzoffiana. Compounds 1 and 2 possess unusual 1,4,4a,9a
      tetrahydrofluoren-9-one and bicyclo[3.3.0]octanedione skeletons, respectively,
      whereas compound 3 is a stilbenolignan belonging to a very rare structural class
      of plant secondary metabolites. Their structures were elucidated by spectroscopic
      analyses. Compounds 1-3 exhibited moderate inhibitory activity against alpha
      glucosidase with IC(50) values of 16.9 microM (1), 23.7 microM (2) and 12.8
      microM (3), respectively.

PMID- 20156630
TI  - Research on adaptive temperature control in sound field induced by self-focused
      concave spherical transducer.
AB  - Temperature control of hyperthermia treatments is generally implemented with
      multipoint feedback system comprised of phased-array transducer, which is
      complicated and high cost. Our simulations to the acoustic field induced by a
      self-focused concave spherical transducer (0.5MHz, 9cm aperture width, 8.0cm
      focal length) show that the distribution of temperature can keep the same "cigar
      shape" in the focal region during ultrasound insonation. Based on the
      characteristic of the temperature change, a two-dimensional model of a "cigar
      shape" tumor is designed and tested through numerical simulation. One single
      point on the border of the "cigar shape" tumor is selected as the control target
      and is controlled at the temperature of 43 degrees C by using a self-tuning
      regulator (STR). Considering the nonlinear effects of biological medium, an
      accurate state-space model obtained via the finite Fourier integral
      transformation to the bioheat equation is presented and used for calculating
      temperature. Computer simulations were performed with the perfusion rates of
      2.0kg/(m(3)s) and 4.5kg/(m(3)s) to the different targets, it was found that the
      temperatures on the border of the "cigar shape" tumor can achieve the desired
      temperature of 43 degrees C by control of one single-point. A larger perfusion
      rate requires a higher power output to obtain the same temperature elevation
      under the same insonation time and needs a higher cost for compensating the
      energy loss carried away by blood flow after steady state. The power output
      increases with the controlled region while achieving the same temperature at the
      same time. Especially, there is no overshoot during temperature elevation and no
      oscillation after steady state. The simulation results demonstrate that the
      proposed approach may offers a way for obtaining a single-point, low-cost
      hyperthermia system.

PMID- 20156631
TI  - Alternative estimate of source distribution in microbial source tracking using
      posterior probabilities.
AB  - Microbial source tracking (MST) is a procedure used to determine the relative
      contributions of humans and animals to fecal microbial contamination of surface
      waters in a given watershed. Studies of MST methodology have focused on
      optimizing sampling, laboratory, and statistical analysis methods in order to
      improve the reliability of determining which sources contributed most to surface
      water fecal contaminant. The usual approach for estimating a source distribution
      of microbial contamination is to classify water sample microbial isolates into
      discrete source categories and calculate the proportion of these isolates in each
      source category. The set of proportions is an estimate of the contaminant source
      distribution. In this paper we propose and compare an alternative method for
      estimating a source distribution-averaging posterior probabilities of source
      identity across isolates. We conducted a Monte Carlo simulation covering a wide
      variety of watershed scenarios to compare the two methods. The results show that
      averaging source posterior probabilities across isolates leads to more accurate
      source distribution estimates than proportions that follow classification.

PMID- 20156632
TI  - Optimization of nano-scale nickel/iron particles for the reduction of high
      concentration chlorinated aliphatic hydrocarbon solutions.
AB  - The use of nano-scale particles as a means of environmental remediation still
      provides a comparatively novel approach for the treatment of contaminated waters.
      The current study compares the reactivity of micro-scale Fe, nano-scale Fe and
      nano-scale Ni/Fe (nickel/iron) particles specifically for dechlorination of
      solutions containing 350 mg L(-1) of TCE (concentration measured at a
      contaminated site in Derbyshire, UK). The results indicated that employing 1 g L(
      1) of reactive material for dechlorination in the monometallic form (both micro-
      and nano-scale) exhibited very little reduction capability compared with the
      bimetallic Ni/Fe nano-scale particles, containing 28.9% Ni (in molar), which
      achieved complete dechlorination of the TCE in solution within 576 h. Experiments
      were also performed to determine the optimum bimetallic composition of the Ni/Fe
      particles for TCE reduction. This revealed that 3.2% Ni was the optimum Ni/Fe
      molar ratio for both maximum dehalogenation performance and minimum release of Ni
      into solution. Using particles of the most effective bimetallic composition,
      experiments were carried out to determine the concentration required for optimal
      TCE reduction. Over the range of nano-scale particle concentrations tested (0.1-9
      g L(-1)), reduction rates of TCE increased with greater TCE:nano-scale particle
      ratios. However, a concentration range of 1-3 g L(-1) was selected as the most
      appropriate for site remediation, since more concentrated solutions demonstrated
      only small increases in rates of reaction. Finally, in order to test the long
      term performance and reactivity of the 3.2% Ni/Fe bimetallic nano-scale
      particles, weekly spikes of 350 mg L(-1) TCE were injected into a 3 g L(-1) nano
      scale particle batch reactor. Results showed that the bimetallic nano-scale
      particles had the ability to reduce 1750 mg L(-1) TCE and remained active for at
      least 13 weeks.

PMID- 20156633
TI  - Strongly increasing blood concentrations of lipid-soluble organochlorines in high
      arctic common eiders during incubation fast.
AB  - Female common eiders (Somateria mollissima) starve during the nesting stage and
      may loose 30-45% of their initial body mass, mostly through lipid mobilization.
      In this study, the effects of fasting on the blood concentrations of three lipid
      soluble organochlorines (OCs: polychlorinated biphenyl [PCB]-153; 1-dichloro-2,2
      bis (p-chlorophenyl) ethylene [p,p'-DDE]; and hexachlorobenzene [HCB]) were
      examined in eiders breeding in the high Arctic. Blood samples were taken from
      females (n=47) at day 5 and day 20 of the incubation period. The mean wet weight
      concentrations of PCB-153 and p,p'-DDE increased strongly between day 5 and day
      20 (3.6 and 8.2-fold, respectively), while HCB increased less (1.7-fold). There
      was a strong negative association between daily increase in PCB-153 and clutch
      size, and a weaker relationship for p,p'-DDE, suggesting that maternal transfer
      to the eggs is a significant pathway of elimination of OCs in eiders. Moreover,
      poor body condition (body mass controlled for body size) late in the incubation
      period was associated with strong daily increase of both p,p'-DDE and PCB-153,
      which may suggest that the release of these compounds increases when lipid
      reserves become depleted. For HCB, the increase was mainly associated with
      increase in blood lipid concentrations, and weakly to the amount of burned
      lipids. The causes for the differences between the compounds are, however, poorly
      understood. Although the absolute levels of OCs in eiders were relatively low,
      their rapid build up during incubation is worrying as it coincides with poor body
      condition and weakened immune systems.

PMID- 20156634
TI  - Contamination levels and congener distribution of PCDDs, PCDFs and dioxin-like
      PCBs in buffalo's milk from Caserta province (Italy).
AB  - An extraordinary plan of official control was carried out in 2008 in Campania
      (Italy) with the aim to monitor polychlorinated dibenzo-p-dioxins (PCDDs),
      dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) levels
      in buffalo milk and to detect the contaminated farms, most of which are located
      in Caserta province. For these companies has been ordered seizure and execution
      of additional analyses has been requested in farms falling in the nearness,
      within a distance of 3km, for a total of 304 farms examined. Moreover, all non
      compliant farms were subjected to a periodic sampling in order to monitor trends
      in the levels of contamination. In this paper the distribution and the
      concentrations of 17 PCDD/Fs and 12 dioxin-like PCBs in 460 samples of buffalo
      milk collected in the province of Caserta (Italy) are presented. The range of WHO
      TEQ values for the PCDD/Fs in milk was 0.17pgTEQg(-1)fat and 87.0pgTEQg(-1)fat
      with a mean value 3.63pgTEQg(-1)fat and medium value 2.25pgTEQg(-1)fat. The
      concentrations of dioxin-like PCBs in the analysed samples ranged from
      0.21pgTEQg(-1)fat to 15.9pgTEQg(-1)fat and the WHO-TEQ values of sum of PCDDs,
      PCDFs and dl-PCBs ranged from 0.45pgTEQg(-1)fat to 103.0pgTEQg(-1)fat. The geo
      referencing analysis allowed to individuate a restricted area of the region
      object of the present study where is located the majority of the non-compliant
      farms. The study of the congeners distribution has finally suggested that the
      likely cause of contamination is to be attributed to the illegal burning of
      waste.

PMID- 20156635
TI  - Sorption and mineralization of organic pollutants during different stages of
      composting.
AB  - The organic pollutant (OP) content is a key factor when determining compost
      quality. The OPs present in feedstock materials may either be degraded during
      composting or stabilized in the compost by sorption interactions with organic
      matter (OM), which may reduce the availability of OP to microorganism
      degradation. It is particularly important to identify the key stages during
      composting that are involved in OP mineralization so as to be able to optimize
      the composting process and determine whether OP sorption on OM is a limiting
      factor to OP mineralization. Four (14)C-labeled OPs were used during the study: a
      polycyclic aromatic hydrocarbon (fluoranthene), two surfactants (4-n-nonylphenol 
      NP and sodium linear dodecylbenzene sulfonate - LAS) and a herbicide
      (glyphosate). The potential for compost microflora to degrade OP, and compost
      sorption properties, were characterized at different stages of composting. The
      highest levels of LAS and glyphosate mineralization were found during the
      thermophilic stage, at the beginning of maturation for NP and at the end of
      maturation for fluoranthene. A specific microflora was probably involved in the
      biodegradation of fluoranthene while NP, LAS and glyphosate mineralization were
      linked to total microbial activity. OP sorption on compost was linked to their
      hydrophobicity, decreasing in the order: fluoranthene>NP>LAS>glyphosate.
      Moreover, sorption decreased as compost maturity increased, except for
      glyphosate. The sorption coefficients were positively correlated to
      mineralization kinetics parameters for NP, LAS and glyphosate, suggesting a
      positive effect of sorption on increasing mineralization rates.

PMID- 20156636
TI  - Diurnal variations in the occurrence and the fate of hormones and antibiotics in
      activated sludge wastewater treatment in Oslo, Norway.
AB  - We present an assessment of the dynamics in the influent concentration of
      hormones (estrone, estriol) and antibiotics (trimethoprim, sulfamethoxazole,
      tetracycline, ciprofloxacin) in the liquid phase including the efficiency of
      biological municipal wastewater treatment. The concentration of estradiol, 17
      alpha-ethinylestradiol, doxycycline, oxytetracycline, demeclocycline,
      chlortetracycline, cefuroxime, cyclophosphamide, and ifosfamide were below the
      limit of detection in all of the sewage samples collected within this study. Two
      different types of diurnal variation pattern were identified in the influent mass
      loads of selected antibiotics and hormones that effectively correlate with daily
      drug administration patterns and with the expected maximum human hormone release,
      respectively. The occurrence of natural hormones and antimicrobials, administered
      every 12 hours, shows a daily trend of decreasing contaminant mass load, having
      the maximum values in the morning hours. The occurrence of antibiotics, typically
      administered every 8 hours, indicates a daily peak value in samples collected
      under the highest hydraulic loading. The efficiency of biological removal of both
      hormones and antibiotics is shown to be limited. Compared to the values obtained
      in the influent samples, increased concentrations are observed in the
      biologically treated effluent for trimethoprim, sulfamethoxazole and
      ciprofloxacin, mainly as a result of deconjugation processes. Ciprofloxacin is
      shown as the predominant antimicrobial compound in the effluent, and it is
      present at quantities approximately 10 fold greater than the total mass of the
      other of the compounds due to poor removal efficiency and alternating solid
      liquid partitioning behaviour. Our results suggest that, to increase the micro
      pollutant removal and the chemical dosing efficiency in enhanced tertiary
      treatment, significant benefits can be derived from the optimisation of reactor
      design and the development of control schemes that accounts for diurnal secondary
      effluent micro-pollutant and hydraulic loading patterns.

PMID- 20156637
TI  - Structure validation of an integrated waterworks model for trihalomethanes
      simulation by applying regional sensitivity analysis.
AB  - A previously developed integrated waterworks model for trihalomethanes simulation
      was validated by applying a new framework for comprehensive model structure
      validation. The proposed framework followed the procedure of regional sensitivity
      analysis and also involved correlation analysis and frequency distribution
      analysis. Through such an analysis framework, a deep insight into model structure
      and parameters could be gained besides the traditional focuses on model
      validation, i.e. model performance and rationality of model parameters. The
      integrated waterworks model, to which the framework was applied, was proved to
      give good predictions of the simulated variables, and the identified values of
      model parameters coincided well with the reported values in the literature. The
      model was also found to have a large proportion of sensitive parameters, no
      distinct correlations among parameters, and thus a balanced structure. Moreover,
      most of the sensitive parameters could be well identified and the associated
      uncertainties significantly reduced. A detailed investigation into the
      sensitivity, identifiability, and uncertainty of model parameters showed that the
      model conceptualization was in good agreement with accepted scientific principles
      and anticipated system behaviors. All these results, therefore, supported the
      validity and trustworthiness of the model. In addition, further opportunities for
      refining the model were also proposed.

PMID- 20156638
TI  - Measurement and source identification of polycyclic aromatic hydrocarbons (PAHs)
      in the aerosol in Xi'an, China, by using automated column chromatography and
      applying positive matrix factorization (PMF).
AB  - In this study, we measured polycyclic aromatic hydrocarbons (PAHs) in aerosols in
      Xi'an, China from 2005 to 2007, by using a modified Soxhlet extraction followed
      by a clean-up procedure using automated column chromatography followed by
      HPLC/fluorescence detection. The sources of PAHs were apportioned by using the
      positive matrix factorization (PMF) method. The PM(10) concentration in winter
      (161.1+/-66.4microgm(-3), n=242) was 1.5 times higher than that in summer
      (110.9+/-34.7microgm(-3), n=248). SigmaPAH concentrations, which are the sum of
      the concentrations of all detected PAHs, in winter (344.2+/-149.7ngm(-3), n=45)
      was 2.5 times higher than that in summer (136.7+/-56.7ngm(-3), n=24) in this
      study. These strong seasonal variations in atmospheric PAH concentration are
      possibly due to coal combustion for residential heating. According to the source
      apportionment with PMF method in this study, the major sources of PAHs in Xi'an
      are categorized as (1) mobile sources such as vehicle exhaust that constantly
      contribute to PAH pollution, and (2) stationary sources such as coal combustion
      that have a large contribution to PAH pollution in winter.

PMID- 20156639
TI  - Interactions between toxic chemicals and natural environmental factors--a meta
      analysis and case studies.
AB  - The paper addresses problems arising from effects of natural environmental
      factors on toxicity of pollutants to organisms. Most studies on interactions
      between toxicants and natural factors, including those completed in the EU
      project NoMiracle (Novel Methods for Integrated Risk Assessment of Cumulative
      Stressors in Europe) described herein, showed that effects of toxic chemicals on
      organisms can differ vastly depending purely on external conditions. We compiled
      data from 61 studies on effects of temperature, moisture and dissolved oxygen on
      toxicity of a range of chemicals representing pesticides, polycyclic aromatic
      hydrocarbons, plant protection products of bacterial origin and trace metals. In
      62.3% cases significant interactions (p< or =0.05 or less) between natural
      factors and chemicals were found, reaching 100% for the effect of dissolved
      oxygen on toxicity of waterborne chemicals. The meta-analysis of the 61 studies
      showed that the null hypothesis assuming no interactions between toxic chemicals
      and natural environmental factors should be rejected at p=2.7 x 10(-82)
      (truncated product method probability). In a few cases of more complex
      experimental designs, also second-order interactions were found, indicating that
      natural factors can modify interactions among chemicals. Such data emphasize the
      necessity of including information on natural factors and their variation in time
      and across geographic regions in ecological risk assessment. This can be done
      only if appropriate ecotoxicological test designs are used, in which test
      organisms are exposed to toxicants at a range of environmental conditions. We
      advocate designing such tests for the second-tier ecological risk assessment
      procedures.

PMID- 20156640
TI  - Influence of initial pesticide concentrations and plant population density on
      dimethomorph toxicity and removal by two duckweed species.
AB  - Aquatic plants take up, transform and sequester organic contaminants and may
      therefore be used in phytoremediation for the removal of pollutants from
      wastewaters. A better understanding of factors affecting the rate of contaminant
      uptake by aquatic plants is needed to improve engineered systems for removal of
      pollutants from wastewaters. This work focused on the influence of initial
      concentrations of pesticide and population density of plants on toxicity and
      uptake of the fungicide dimethomorph by two duckweed species. An increased
      sensitivity to dimethomorph was observed with increasing duckweed population
      density. Less light, due to crowding, may explain this higher sensitivity and
      reduced removal rate. A positive relationship was also found between toxicity or
      contaminant uptake and initial pesticide concentration with a maximal removal of
      41 and 26 microg g(-1) fresh weight of dimethomorph (at 600 microg L(-1) of
      dimethomorph and an initial density of 0.10g E-flask(-1)) by Lemna minor and
      Spirodela polyrhiza, respectively. This research also indicated that these
      aquatic plants can efficiently eliminate organic contaminants and may ultimately
      serve as phytoremediation agents in the natural environment.

PMID- 20156641
TI  - Proteomics of microparticles after deep venous thrombosis.
AB  - BACKGROUND: Microparticles (MP) are submicron size membrane vesicles released
      from activated cells that are associated with thrombosis and inflammation. MP
      present diverse biological expressions that may be linked to a unique subset of
      proteins derived from their origin cells. METHODS: To identify these proteins,
      plasma samples were taken from 9 patients with deep venous thrombosis (DVT)
      documented by duplex ultrasound, 9 with leg pain but negative for DVT by duplex,
      and 6 healthy controls without a history of thrombosis, for fold variation. MP
      were extracted from platelet-poor plasma, digested separately with trypsin and
      tagged using iTRAQ reagents. The digests were subjected to 2-D LC separation
      followed by MALDI tandem mass spectrometry. Peak lists were generated and
      searched against all human sequences. For protein identification, a minimum of
      two peptides at 95% confidence was required. Later, iTRAQ ratios were generated
      comparing relative protein levels of DVT patients to baseline. The proteomic
      analysis was performed twice for each blood sample. Proteins were considered
      elevated or depressed if the iTRAQ ratio (R) deviated by 20% change from normal
      and a p-value less than 0.05. RESULTS: Two proteins (Galectin-3 Binding Protein,
      [Gal3BP], R=1.76 and Alpha-2 macroglobulin [A2M] R=1.57) were differentially
      expressed on DVT patients. Nine proteins were depleted including fibrinogen beta
      and gamma chain precursors (R=0.65). CONCLUSIONS: These proteins influence
      thrombosis through inflammation, cell shedding, inhibition of fibrinolysis and
      hemostatic plug formation. Further studies are needed to confirm the mechanistic
      role of these proteins in the pathogenesis of venous thrombosis in humans.

PMID- 20156642
TI  - Microsatellite (GT)(n) is part of the von Willebrand factor (VWF) promoter region
      that influences the glucocorticoid-induced increase in VWF in Cushing's syndrome.
AB  - INTRODUCTION: The cortisol-induced increase in von Willebrand factor (VWF) in
      Cushing's syndrome (CS) seems to depend on single nucleotide polymorphisms (SNPs)
      of the VWF promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being the
      susceptible pattern. MATERIALS AND METHODS: This study focused on a new variable
      region of the VWF promoter, the -2144(GT)(n) locus, to establish whether
      different GT-repeat lengths are also involved in modulating the cortisol-induced
      increase in VWF. Sixty-nine CS patients were investigated, divided into groups A
      (high VWF) and B (normal VWF). RESULTS: Analysing the (GT)(n) locus revealed a
      similar allele distribution in CS patients and normal subjects, (GT)(n) variants
      ranging from 15 to 24 repeats and (GT)(19) and (GT)(21) being the two most
      represented. However, when groups A and B were analysed separately, a different
      allele distribution was observed: short GT-repeats (15-19, GT(S)) were more
      frequent in group A, long GT-repeats (20-24, GT(L)) in group B (p=0.01). About
      genotype distributions, (GT)(S)/(GT)(S) was higher in group A and rare in group B
      (22.5% and 3.4%, respectively), whereas (GT)(L)/(GT)(L) was higher in group B
      than in group A (55.2%, 27.5%) (p=0.021). Odds-ratio analysis revealed a risk of
      a cortisol-dependent increase in VWF three times higher for alleles (GT)(S) than
      for (GT)(L), and 13-fold for genotype (GT)(S)/(GT)(S) respect to (GT)(L)/(GT)(L).
      CONCLUSIONS: In conclusion, not only the SNPs haplotypes in the VWF gene
      promoter, but also the variable-length (GT)(n) locus predict the risk of
      developing high VWF levels under conditions of glucocorticoid excess; the
      combination of (GT)(S) and haplotype 1 represents the susceptible pattern.

PMID- 20156643
TI  - Factor VIIa interaction with endothelial cells and endothelial cell protein C
      receptor.
AB  - Plasma coagulation factor VIIa (FVIIa) initiates the coagulation cascade by
      binding to its cofactor, tissue factor (TF) on cell surfaces, which eventually
      leads to fibrin deposition and platelet activation. Recent studies showed that
      FVIIa also binds to endothelial cell protein C receptor (EPCR), a known cellular
      receptor for anticoagulant protein C?activated protein C, on the endothelium. The
      present article reviews our current knowledge of FVIIa interaction with EPCR and
      discusses the potential significance of this interaction in hemostasis, treatment
      of bleeding disorders with pharmacological doses of FVIIa and FVIIa clearance.

PMID- 20156644
TI  - Recent estimates of the structure of the factor VIIa (FVIIa)/tissue factor (TF)
      and factor Xa (FXa) ternary complex.
AB  - The putative structure of the Tissue Factor/Factor VIIa/Factor Xa (TF/FVIIa/FXa)
      ternary complex is reconsidered. Two independently derived docking models
      proposed in 2003 (one for our laboratory: CHeA and one from the Scripps
      laboratory: Ss) are dynamically equilibrated for over 10 ns in an electrically
      neutral solution using all-atom molecular dynamics. Although the dynamical models
      (CHeB and Se) differ in atomic detail, there are similarities in that TF is found
      to interact with the gamma-carboxyglutamic acid (Gla) and Epidermal Growth Factor
      like 1 (EGF-1) domains of FXa, and FVIIa is found to interact with the Gla, EGF-2
      and serine protease (SP) domains of FXa in both models. FVIIa does not interact
      with the FXa EGF-1 domain in Se and the EGF domains of FVIIa do not interact with
      FXa in the CHeB. Both models are consistent with experimentally suggested
      contacts between the SP domain of FVIIa with the EGF-2 and SP domains of FXa.

PMID- 20156645
TI  - Plasma levels of von Willebrand factor are increased in patients with
      hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is characterised by inappropriate hypertrophy,
      small-vessel coronary artery disease, myocyte disarray and increased interstitial
      fibrosis. Microvascular dysfunction is a common finding in HCM and its extent has
      been proposed as an important prognostic marker. Plasma von Willebrand factor
      (vWf) is an established marker of endothelial damage or dysfunction; however it
      has scarcely been studied in HCM. We hypothesised that vWf could be raised in
      patients with HCM and be related to different variables associated with severity
      of HCM. METHODS: We included 124 HCM patients, 93 males, aged 48+/-15 years, 59
      healthy control subjects with similar age and sex and 20 patients with ischemic
      heart disease but clinical stability for the last 6 months. A complete history
      and clinical examination was performed, including 12-lead electrocardiogram,
      echocardiography, 24 hours ECG-Holter monitoring, and symptom limited treadmill
      exercise test. Risk factors for sudden death were evaluated. A blinded cardiac
      MRI was performed with late enhanced study with Gadolinium. Plasma vWf levels
      were assayed by commercial ELISA. RESULTS: Patients showed higher levels of vWf
      (140.0+/-65.0 UI/ml vs 105.0+/-51.0 UI/ml, p<0.001) even after adjusting for ABO
      blood group. vWf levels were found raised in patients with severe functional
      class (168.4+/-65.9 UI/mL vs 132.4+/-60.7 UI/mL, p=0.020), atrial fibrillation
      (175.8+/-69.4 UI/mL vs 133.0+/-59.0 UI/mL, p=0.005), hypertension (161.4+/-60.8
      vs 128.9+/-60.5, p=0.010) obstruction (153.9+/-67.9 vs 128.2+/-57.4 UI/mL,
      p=0.046) and non sustained ventricular tachycardia (159.3+/-59.1 vs 133.0+/-63.0,
      p=0.049). vWf correlated with age (r:0.26; p=0.006) and obstruction (r:0.22;
      p=0.021). CONCLUSIONS: We show, for the first time, patients with HCM present
      significantly raised levels of vWf. These are associated with different
      conditions related to the severity of the disease.

PMID- 20156646
TI  - Enterococcus faecalis cellulitis/fasciitis after hypospadias surgery.
AB  - We describe a case of Enterococcus faecalis-associated cellulitis/fasciitis after
      hypospadias surgery.

PMID- 20156647
TI  - A minority of men with spinal cord injury have normal semen quality--can we learn
      from them? A case-control study.
AB  - OBJECTIVES: To determine factors that may help predict normal semen quality in
      this unique population of male patients, we examined our large database of men
      with spinal cord injury (SCI). Most men with SCI have abnormal semen quality;
      however, a small minority retain normal semen parameters. METHODS: A
      retrospective analysis was performed on semen retrieval procedures administered
      between 1991 and 2009 in 500 men with SCI. From those men, we selected subjects
      who underwent at least 1 penile vibratory stimulation, electroejaculation, or
      masturbation procedure resulting in antegrade ejaculation (n = 400). Cases were
      defined as men who, according to World Health Organization criteria, had normal
      semen volume, sperm concentration, sperm motility. Control subjects (CR) were
      defined as all remaining subjects. Risk factors for normal semen parameters were
      evaluated by conditional logistic regression analysis. RESULTS: Of the 400
      subjects evaluated, only 30 had normal semen parameters. These 30 CS subjects
      were matched to 120 CR subjects. Analysis of risk factors revealed that
      incomplete lesion of the spinal cord (ASIA B to D) was significantly associated
      with the presence of normal sperm parameters (odds ratio 2.6 [95% confidence
      interval 1.1-6.1], P = .028). CS subjects were also more likely to be able to
      collect their samples via masturbation (odds ratio 2.7 [95% confidence interval
      1.1-7.1], P = .037). Other risk factors evaluated were not predictive of normal
      semen parameters. CONCLUSIONS: This retrospective, case-control study, performed
      on a large group of subjects, showed that completeness of SCI is an important
      risk factor influencing semen quality.

PMID- 20156648
TI  - Potent cytotoxic effect of a novel nuclear factor-kappaB inhibitor
      dehydroxymethylepoxyquinomicin on human bladder cancer cells producing various
      cytokines.
AB  - OBJECTIVES: To explore the potential therapeutic effects of the nuclear factor
      kappaB (NF-kappaB) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ). KU-19-19
      cells, originally derived from a patient with invasive bladder cancer who
      exhibited marked leukocytosis, produce multiple cytokines. This model of
      clinically advanced bladder cancer, in which NF-kappaB is constitutively
      activated, was used in this study. METHODS: Expression of p65 protein in
      fractionated KU-19-19 cells was determined by Western blotting analysis. DNA
      binding activity of NF-kappaB was detected by electrophoretic mobility shift
      assay. The cytotoxic effects and induction of apoptosis by DHMEQ were analyzed,
      and cytokines in the supernatant of KU-19-19 cells cultured with or without DHMEQ
      were measured by enzyme-linked immunosorbent assay (ELISA). Athymic nude mice
      bearing KU-19-19 subcutaneous tumors were subjected to intraperitoneal
      administration of 2 mg/kg/d DHMEQ for 3 weeks. Tumor growth was monitored and
      microvessel density, vascular endothelial growth factor expression, and the
      apoptotic index of tumors were evaluated by tissue immunohistochemistry. RESULTS:
      NF-kappaB was constitutively activated in KU-19-19 cells. DHMEQ reversibly
      inhibited the DNA-binding activity of NF-kappaB by blocking its nuclear
      translocation. Both cell viability and production of cytokines were significantly
      and dose-dependently suppressed by DHMEQ, and significant apoptosis was also
      induced. In in vivo studies, the mean tumor volume in mice treated with DHMEQ was
      significantly smaller than in controls. Immunohistochemical analysis of tumors
      revealed marked reduction in microvessel density, vascular endothelial growth
      factor expression, and induction of apoptosis. CONCLUSIONS: Blockade of NF-kappaB
      function by DHMEQ may be a useful new molecular targeting treatment for highly
      aggressive bladder cancer.

PMID- 20156649
TI  - Nephrocutaneous bypass in ureteral obstruction.
AB  - OBJECTIVES: To describe our experiences with nephrocutaneous bypass and to assess
      the role of this procedure as a mean of urinary diversion in patients with
      incurable ureteral obstruction who are not appropriate candidates for
      subcutaneous pyelovesical bypass. METHODS: Nephrocutaneous bypass was performed
      on 15 (12 male, 3 female) patients with incurable ureteral obstruction of
      malignant (n = 13; 87%) or benign (n = 2; 13%) etiology. Only patients with a
      significant disturbance of the bladder/sphincter-system were eligible for the
      procedure. RESULTS: In total, 29 stents were applied using this technique. No
      major complications were observed perioperatively. The operating time for
      bilateral nephrocutaneous bypass was 74 (46-102) minutes and for unilateral
      bypass (1 patient) 38 minutes. Time of indwelling percutaneous nephrostomy before
      application of nephrocutaneous bypass was 190 (40-870) days. The patients who
      survived have a mean follow-up of 27 months, whereas for those patients who died
      the mean follow-up was 7.8 months. Nephrocutaneous bypass resulted in an improved
      renal function in all patients. Quality of life improvement was reported by all
      patients, and the objective criteria of "useful life" were met by 13 patients
      (87%). CONCLUSIONS: Nephrocutaneous bypass is a safe and feasible method to
      provide effective pyelovesical drainage of urine in patients who have a short
      term life expectancy, who are in poor general conditions, or otherwise would need
      a permanent nephrostomy drainage. The technique offers patients a higher
      mobility, increased independence resulting in higher quality of life during their
      final period of life, and may also be applied in nonmalignant patients after
      careful consideration of alternative urinary diversions.

PMID- 20156650
TI  - Value of transrectal ultrasonography in female traumatic urethral injuries.
AB  - OBJECTIVES: To estimate the value of transrectal ultrasonography (TRUS) in
      traumatic urethral injuries of various types in females. METHODS: A total of 30
      female patients with symptoms of urethral injuries after trauma underwent TRUS
      between January 2005 and July 2008. Of them, 28 patients with operative
      indications undertook operation; the other 2 received conservative management and
      then a follow-up ultrasonography. All outcomes were used to validate the results
      of TRUS. RESULTS: Urethral injuries were clearly observed in 30 cases with TRUS.
      The continuity of urethral wall, unblocking of urethral lumen, and homogeneous
      echo of surrounding structures had been changed. Urethral injuries varied in
      types, including urethrovaginal fistula, urethral stricture, urethral rupture,
      and urethral hematoma. It was common to find several injury patterns
      simultaneously in 1 patient. The outcomes in 28 cases with operative indications
      were consistent with results of surgery. The other 2 cases were diagnosed as
      urethral hematoma by TRUS which disappeared in a follow-up sonography after 3
      months' conservative management. CONCLUSIONS: TRUS is a reliable technique to
      exhibit abnormalities in injured urethra associated with trauma in female.

PMID- 20156651
TI  - Differential roles of M2 and M3 muscarinic receptor subtypes in modulation of
      bladder afferent activity in rats.
AB  - OBJECTIVES: To investigate the effects of various muscarinic acetylcholine
      receptor (mAChR) antagonists, including selective M2 and M3 mAChR antagonists, on
      bladder overactivity. It has been proposed that the urothelium modulates the
      activity of bladder afferent pathways. However, the differential roles of mAChR
      subtypes in local bladder afferent activation remain unclear. METHODS: Cystometry
      was performed in urethane-anesthetized female rats. We examined the effects of
      intravesical administration of antimuscarinic agents (nonselective mAChR
      antagonists: atropine sulfate, tolterodine tartrate, and propiverine
      hydrochloride; M2-selective antagonists: dimethindene maleate and methoctramine
      hemihydrate; M3-selective antagonists: darifenacin hydrobromide and 4-DAMP) on
      bladder overactivity induced by oxotremorine-M (oxo-M; nonselective mAChR
      agonist). RESULTS: Intravesical administration of oxo-M (200 microM) elicited
      bladder overactivity as evidenced by decreased intercontraction interval, bladder
      capacity, and pressure threshold. These effects were blocked by intravesical
      administration of nonselective or M2-selective antagonists (30-60 microM),
      whereas M3-selective antagonists (150 microM) did not suppress the overactivity.
      When instilled intravesically by itself, none of the antimuscarinic agents
      (nonselective, M2-selective or M3-selective antagonists) affected any cystometric
      parameters. CONCLUSIONS: The M2 mAChR subtype plays an important role in the
      local cholinergic modulation of bladder afferent activity that contributes to
      bladder overactivity in normal rats. Therefore, it is expected that
      antimuscarinic agents that have antagonistic activity against M2 mAChR can be
      more beneficial for the treatment of patients with overactive bladder if enhanced
      acetylcholine mechanisms are involved in pathogenesis of overactive bladder.

PMID- 20156654
TI  - Complications of the AdVance transobturator male sling in the treatment of male
      stress urinary incontinence.
AB  - OBJECTIVE: To evaluate prospectively the complication rate of the retrourethral
      transobturator sling (AdVance sling) for the functional treatment of male stress
      urinary incontinence (SUI). METHODS: In 230 patients with SUI due to nonintrinsic
      sphincter deficiency (without direct sphincter lesion) after radical
      prostatectomy (n=213), radical cystoprostatectomy with ileal neobladder (n=2) and
      transurethral resection of the prostate (n=15) a retrourethral transobturator
      sling was implanted. Patients were followed up for a median of 17 months (range,
      4-42 months) with regard to intraoperative, early postoperative, and midterm
      postoperative complications. RESULTS: Overall complication rate of the AdVance
      sling was 23.9%. Despite one accidental sling misplacement, no intraoperative
      complication occurred. Forty-nine patients (21.3%) experienced urinary retention
      postsurgery. Two slings were explanted (0.9%), 1 due to initial wrong placement
      and the other due to a symphysitis, attributed to a Guillain-Barre syndrome and
      not to a sling infection. One sling was transected (0.4%) due to slippage of the
      sling with obstruction of the urethra. Further complications were local wound
      infection (0.4%), urinary infection with fever (0.4%), and persistent moderate
      perineal pain (0.4%). There was no correlation between postoperative acute
      urinary retention and age at sling implantation, time of incontinence before
      sling implantation, preoperative daily pad use, or prior invasive incontinence
      treatment, respectively. CONCLUSIONS: The retrourethral transobturator AdVance
      sling is a safe treatment option for male nonintrinsic sphincter deficiency SUI,
      with the main postoperative complication being transient acute urinary retention.
      Severe intra- and postoperative complications are rare and sling explantation
      rate is very low.

PMID- 20156655
TI  - Scrotal approach to both palpable and impalpable undescended testes: should it
      become our first choice?
AB  - OBJECTIVES: To determine the advantages of scrotal incision in the treatment of
      undescended testis. Undescended testis is a common pediatric condition and is
      conventionally managed surgically by orchidopexy. A single scrotal incision
      orchidopexy has become accepted as a valid approach for patients with palpable
      undescended testicles. Because this approach also allows easy detection of
      atrophic testes or testicular remnants, it recently has also emerged as an
      alternative initial surgical approach to impalpable undescended testicles.
      METHODS: All orchidopexies performed between 2004 and 2008 at our university
      hospital were prospectively included in this study. A total of 194 scrotal
      orchidopexies were performed in 154 patients (mean age, 71 months; range, 4-229
      months). In all cases a scrotal approach was chosen irrespective of the initial
      position or presence of an open processus vaginalis. Testicular position was
      examined at follow-up after a mean period of 10 months (3-22 months). RESULTS:
      Overall, 36 of the 46 impalpable testicles (78%) could be diagnosed and treated
      accordingly, using only a scrotal incision. Conversion to laparoscopy was needed
      in 4 cases. A limited number of postoperative complications were seen. In all
      cases, the testes were palpable and remained in the scrotum on follow-up.
      CONCLUSIONS: Initial single scrotal incision can be recommended for orchidopexy,
      even in the more difficult cases of impalpable undescended testes. Advantages
      seem to include shorter operative time, a cosmetically appealing single incision,
      and possibly less pain. The scrotal incision technique significantly reduces the
      need for laparoscopy in impalpable testes. Surprisingly, it even allows
      successful orchidopexy of abdominal testes, provided an open processus is
      present.

PMID- 20156656
TI  - Laparoscopic pyeloplasty: comparison between retroperitoneoscopic and
      transperitoneal approach.
AB  - OBJECTIVE: To compare both approaches of laparoscopic pyeloplasty,
      transperitoneal vs retroperitoneoscopy. METHODS: A total of 65 procedures were
      performed in 62 patients, 36 females and 26 males. Laparoscopic pyeloplasty with
      Anderson Hynes technique was performed transperitoneal in 34 cases and
      retroperitoneal in 31 cases. Parameters studied were the operative duration, the
      rate of conversion to open approach, transposition of crossing vessel,
      complications and reintervention, results, and the duration of hospitalization.
      Then, overall success rate for both approaches was evaluated in the presence or
      absence of crossing vessels, and if transposition of crossing vessel was
      performed vs without. RESULTS: The overall success rate for both procedures was
      85% (87% for the retroperitoneal vs 82% for the transperitoneal approach). The
      mean operative duration was 231.69 +/- 59.97 and 194.76 +/- 25.37 minutes for the
      retroperitoneal and transperitoneal approaches, respectively (P = .029). The rate
      of conversion was 19.35% (6 of 31) and 2.9% (1 of 34) for the retroperitoneal and
      transperitoneal approaches, respectively (P = .047). No significant statistical
      difference was noted between both techniques related to the age of patient, the
      hospital stay, and intraoperative and postoperative complications. Transposition
      of crossing vessel had no effect on the results (81.25% with transposition and
      80% if not, P = .93). CONCLUSIONS: Retroperitoneoscopic approach is associated
      with longer operative time and more conversion rate than transperitoneoscopy.
      However, the overall outcomes of laparoscopic transperitoneal pyeloplasty vs
      retroperitoneoscopic were comparable.

PMID- 20156657
TI  - Speaking in multiple languages: neural correlates of language proficiency in
      multilingual word production.
AB  - The human brain has the fascinating ability to represent and to process several
      languages. Although the first and further languages activate partially different
      brain networks, the linguistic factors underlying these differences in language
      processing have to be further specified. We investigated the neural correlates of
      language proficiency in a homogeneous sample of multilingual native Ladin
      speakers from a mountain valley in South Tyrol, Italy, who speak Italian as
      second language at a high level, and English at an intermediate level. In a
      constrained word production task under functional magnetic resonance imaging
      (fMRI), participants had to name pictures of objects in Ladin, Italian and
      English in separate blocks. Overall, multilingual word production activated a
      common set of brain areas dedicated to known subcomponents of picture naming. In
      comparison to English, the fluently spoken languages Ladin and Italian were
      associated with enhanced right prefrontal activity. In addition, the MR signal in
      right prefrontal cortex correlated with naming accuracy as a measure of language
      proficiency. Our results demonstrate the significance of right prefrontal areas
      for language proficiency. Based on the role of these areas for cognitive control,
      our findings suggest that right prefrontal cortex supports language proficiency
      by effectively supervising word retrieval.

PMID- 20156658
TI  - NF-kappaB1 contributes to T cell-mediated control of Toxoplasma gondii in the
      CNS.
AB  - In this study, the role of NF-kappaB1 was examined during toxoplasmosis. While
      wildtype BALB/c mice generated protective responses, NF-kappaB1(-/-) mice
      developed Toxoplasmic encephalitis, characterized by increased parasite burden
      and necrosis in the brain. Susceptibility was primarily associated with a local
      decrease in the number of CD8(+) T cells and IFN-gamma production, while
      accessory cell function appeared intact in NF-kappaB1(-/-) mice. Consistent with
      these findings, T cell transfer studies revealed that NF-kappaB1(-/-) T cells
      provided SCID mice less protection than wildtype T cells. These results
      demonstrate an intrinsic role for NF-kappaB1 in T cell-mediated immunity to
      Toxoplasmagondii.

PMID- 20156660
TI  - Biocontrol of Aspergillus flavus on peanut kernels by use of a strain of marine
      Bacillus megaterium.
AB  - A strain of marine Bacillus megaterium isolated from the Yellow Sea of East China
      was evaluated for its activity in reducing postharvest decay of peanut kernels
      caused by Aspergillus flavus in in vitro and in vivo tests. The results showed
      that the concentrations of antagonist had a significant effect on biocontrol
      effectiveness in vivo: when the concentration of the washed bacteria cell
      suspension was used at 1x10(9)CFU/ml, the percentage rate of rot of peanut
      kernels was 31.67%+/-2.89%, which was markedly lower than that treated with water
      (the control) after 7days of incubation at 28 degrees C. The results also showed
      that unwashed cell culture of B. megaterium was as effective as the washed cell
      suspension, and better biocontrol was obtained when longer incubation time of B.
      megaterium was applied. When the incubation time of B. megaterium was 60-h, the
      rate of decay declined to 41.67%+/-2.89%. Furthermore, relative to the expression
      of 18S rRNA, the mRNA abundances of aflR gene and aflS gene in the experiment
      group were 0.28+/-0.03 and 0.024+/-0.005 respectively, indicating that this
      strain of B. megaterium could significantly reduce the biosynthesis of aflatoxins
      and expression of aflR gene and aflS gene (p<0.01). To the best of our knowledge,
      this is a first report demonstrating that the marine bacterium B. megaterium
      could be used as a biocontrol agent against postharvest fungal disease caused by
      A. flavus.

PMID- 20156659
TI  - Recommendations for adult and paediatric cardiologists on obtaining additional
      qualification in "Adults with Congenital Heart Disease" (ACHD).
AB  - BACKGROUND: The number of adult congenital heart disease (ACHD) patients will be
      larger in the medium to long term than that of children and adolescents with
      congenital heart disease. The present structures for the medical care of ACHD
      patients are not sufficient and need to be improved. Therefore the Task Force
      aimed at developing recommendations for adult and paediatric cardiologists to
      acquire the additional qualification "Adults with Congenital Heart Disease"
      (ACDH). METHODS: The members of the interdisciplinary Task Force were selected on
      the basis of their special clinical, scientific and organisational expertise. The
      leading author submitted a draft version, which was revised by a sub-group of the
      interdisciplinary Task Force. It was subsequently agreed upon and re-circulated
      by all the members of the Task Force. The recommendations were then presented to
      the relevant committees of all participating associations and groups and approved
      following detailed discussion. RESULTS: A training programme for acquiring an
      additional qualification in the treatment of adults with congenital heart disease
      was created successfully. CONCLUSIONS: The medical care of adults with congenital
      heart disease is a sub-speciality in the border area between adult cardiology and
      paediatric cardiology. ACHD cardiologists are to be specially trained experts
      with appropriate knowledge and special skills and experience in the diagnosis and
      therapy of congenital heart disease in adults. ACHD cardiologists should be able
      to recognise and treat problems that occur in adulthood in connection with
      congenital heart disease.

PMID- 20156661
TI  - Persistence of Escherichia coli on injured vegetable plants.
AB  - Minor shoot injury to glasshouse celery, Cos lettuce and chive plants
      significantly increased the persistence of applied Escherichia coli (P<0.05).
      After 1 week, mean counts of about 5 log(10) CFU/g decreased to fewer than 0.5
      log(10) CFU/g on the uninjured plants, compared to 4 log(10) CFU/g or more on
      injured plants. By the end of the 3-week long experiments, counts from the
      uninjured plants were 0.21 log(10) CFU/g or fewer, but 2.8, 2.3 and 5.1 log(10)
      CFU/g on injured Cos lettuce, celery and chive plants, respectively. A field
      experiment using Cos lettuce also showed that shoot injury increased E. coli
      persistence. Counts from the injured plants on days 1, 3, and 7 were, 4.2, 4.1
      and 3.3 log(10) CFU/g, respectively, whereas the uninjured plants returned
      significantly (P<0.05) lower counts on those days, and were 2.8, 2.0 and 1.2
      log(10) CFU/g, respectively. These findings reveal that increased E. coli
      persistence on injured tissue is common to different vegetables and can occur in
      the glasshouse and the field. The implications of this study on vegetable
      production practices are presented.

PMID- 20156662
TI  - Maxillary sinus elevation with an alloplastic material and implants: 11 years of
      clinical and radiologic follow-up.
AB  - PURPOSE: The aim of this retrospective study was to determine the clinical and
      radiologic results, over an 11-year period, of resorbable hydroxyapatite used as
      a bone substitute in maxillary sinus elevation. MATERIALS AND METHODS: Between
      1996 and 2007, we treated 26 patients with maxillary sinus elevation (27 sinuses)
      using resorbable hydroxyapatite and simultaneous insertion of 47 titanium
      implants. Patients were recruited, screened, and accepted or rejected
      sequentially based on specific inclusion/exclusion criteria. Ten months later, 2
      stage surgery and prosthetic rehabilitation were performed. RESULTS: During the
      11-year follow-up period (mean, 6 years), all the implants appeared clinically
      and radiologically integrated. The cumulative survival rate was 100%. During the
      observation period, the resorption of the graft apically to the implant was 1.8
      mm on average. CONCLUSION: The posterior area of the maxilla often represents a
      challenging clinical situation because of either the lack of alveolar bone or the
      structural characteristics of the trabeculae in that specific area. The high
      survival rate of the implants and the stability of the mineralization of the
      graft confirmed that resorbable hydroxyapatite was a suitable material for sinus
      grafting.

PMID- 20156663
TI  - Computer-assisted surgery in the edentulous jaw based on 3 fixed intraoral
      reference points.
AB  - PURPOSE: In computer-assisted implantation surgery, the transfer of prosthodontic
      guided planning to the operative site is usually based on a registration
      template. The precise repositioning of the registration template is crucial for
      high accuracy and is compromised in edentulous jaws. The purpose was to determine
      the in vitro registration and targeting accuracy for surgical navigation in the
      edentulous jaw based on 3 fixed intraoral reference points. MATERIALS AND
      METHODS: Edentulous maxilla and mandible cadaver specimens were provided with 3
      fixed reference-point screws. A resin template with matrices for the fixed
      reference-point screws was produced and connected to a Vogele-Bale-Hohner
      registration mouthpiece and external registration frame with a snap-lock system.
      Surgical implants were planned on computed tomographic data and the corresponding
      dental stone casts were drilled under guidance of an optical navigation system.
      For evaluation of the registration accuracy, fiducial registration error was
      recorded and application accuracy was evaluated by fusion of postsurgical
      computed tomographic scans of the drilled dental stone casts with the presurgical
      planning computed tomogram. RESULTS: In 9 maxillas and 5 mandibles, 14
      registrations and 104 stone cast drillings were performed. The mean fiducial
      registration error was 0.49 +/- 0.14 mm (0.37 to 0.9 mm). The mean total error at
      the tip of the borehole was 0.88 +/- 0.65 mm (0.0 to 4.24 mm). The mean lateral
      errors were 0.51 +/- 0.49 mm (0.0 to 2.80 mm) at the base and 0.46 +/- 0.34 mm
      (0.0 to 1.5 mm) at the tip of the borehole, respectively. The mean angular error
      was 0.83 +/- 0.60 degrees (0.0 to 2.5 degrees ). CONCLUSION: Three fixed
      intraoral reference points successfully support a registration mouthpiece and
      provide in vitro registration and targeting accuracy that is comparable to tooth
      supported registration templates or bone marker registration.

PMID- 20156664
TI  - A novel surgical approach to impacted mandibular third molars to reduce the risk
      of paresthesia: a case series.
AB  - PURPOSE: Extraction of impacted mandibular third molars (M3s) may cause temporary
      or permanent neurosensorial disturbances of the inferior alveolar nerve (IAN).
      Although the incidence of this complication is low, a great range of variability
      has been reported in the literature. Several methods to reduce or eliminate this
      complication have been proposed, such as orthodontic-assisted extraction,
      extraction of the second molar, or intentional odontoectomy. The purpose of this
      series of cases is to present a novel approach for a riskless extraction of
      impacted mandibular M3s in contact with the IAN. MATERIALS AND METHODS: Nine
      consecutive patients (4 male and 5 female; mean age 24.9 years, range 18-43
      years) required the extraction of 10 horizontally or mesioangular impacted
      mandibular M3s. In all cases the M3 was in contact with the IAN with a high risk
      of nerve injury. A staged approached was proposed and accepted by the patients.
      This approach consisted in the surgical removal of the mesial portion of the
      anatomic crown to create adequate space for mesial M3 migration. After the
      migration of the M3 had taken place, the extraction could then be accomplished in
      a second surgical session minimizing neurological risks. RESULTS: All M3s moved
      mesially within 6 months (mean 174.1 days, range 92-354 days) and could be
      successfully removed without any neurological consequences. CONCLUSION: This
      technique may be considered as an alternative approach to the extraction of
      horizontally or mesioangular impacted M3s in proximity to the IAN.

PMID- 20156665
TI  - Inhibition of necrotic actions of nitrogen-containing bisphosphonates (NBPs) and
      their elimination from bone by etidronate (a non-NBP): a proposal for possible
      utilization of etidronate as a substitution drug for NBPs.
AB  - PURPOSE: Nitrogen-containing bisphosphonates (NBPs) have powerful anti-bone
      resorptive effects (ABREs). However, recent clinical applications have disclosed
      an unexpected side effect, osteonecrosis of the jaw. We previously found in mice
      that etidronate (a non-NBP), when coadministered with alendronate (an NBP),
      inhibited the latter's inflammatory effects. However, etidronate also reduced the
      ABRE of alendronate. The present study examined in mice the modulating effects of
      etidronate on the inflammatory and necrotic actions of zoledronate (the NBP with
      the strongest anti-bone-resorptive activity and the highest incidence of
      osteonecrosis of the jaw) and on ABREs of various NBPs including zoledronate.
      MATERIALS AND METHODS: NBPs were subcutaneously injected into ear pinnas of mice
      and ensuing inflammation and necrosis at the site of the injection were
      evaluated. ABREs of NBPs were evaluated by analyzing sclerotic bands induced in
      mouse tibias. RESULTS: Coinjection of etidronate reduced inflammatory and
      necrotic reactions induced by zoledronate, and also reduced the amount of
      zoledronate retained within the ear tissue. When both agents were
      intraperitoneally injected, etidronate reduced the ABRE of zoledronate and those
      of other NBPs. Notably, etidronate reduced the ABRE of zoledronate even when this
      non-NBP was injected 16 hours after the injection of zoledronate. Bone scintigram
      indicated that etidronate reduced the amount of zoledronate that had already
      bound to bone. CONCLUSIONS: These results suggest that etidronate may 1) inhibit
      the entry of NBPs into cells related to inflammation and/or necrosis, 2) inhibit
      the binding of NBPs to bone hydroxyapatite, 3) at least partly eliminate (or
      substitute for) NBPs that have already accumulated within bones, and thus 4) if
      used as a substitution drug for NBPs, be effective at treating or preventing NBP
      associated osteonecrosis of the jaw.

PMID- 20156666
TI  - Diagnosis and management of upper airway obstruction due to lingual hematoma:
      report of a case.

PMID- 20156667
TI  - Temporomandibular joint condylar abnormality: evaluation, treatment planning, and
      surgical approach.

PMID- 20156668
TI  - Desflurane versus sevoflurane to reduce blood loss in maxillofacial surgery.
AB  - PURPOSE: In our study, desflurane was hypothesized to reduce blood loss more than
      sevoflurane, both used with targeted mild controlled hypotension. PATIENTS AND
      METHODS: A total of 20 American Society of Anesthesiologists Class I patients
      undergoing maxillofacial elective surgery for maxillary and mandibular
      osteotomies were randomized to a desflurane group or a sevoflurane group.
      Anesthesia was performed with an end tidal value of the inhaled agent to obtain a
      bispectral index value <30 but without burst-suppression patterns (minimal
      alveolar concentration age-corrected between 0.7 and 0.9). Remifentanil was
      administered at a dose of 0.5 microg x kg(-1) x min(-1) to obtain analgesia and a
      <2 surgical field level in Fromme's modified scale. Sodium-nitroprusside was
      administered on demand to have a surgical field level of <2 when the anesthesia
      plan was not sufficient to achieve this target. The minimal value of the mean
      arterial pressure achievable was 60 mm Hg. RESULTS: In the desflurane group,
      blood loss was more restricted. The hypotensive drug was used in 8 patients in
      the sevoflurane group and 2 patients in the desflurane group. CONCLUSIONS:
      Anesthesia with desflurane can reduce blood loss and could give an acceptable
      surgical field with mild controlled hypotension and with a substantial reduction
      in the vasoactive drug requirement. These data need to be assessed with an
      enlargement of the statistical sample.

PMID- 20156669
TI  - Inferior alveolar nerve paresthesia secondary to orthodontic tooth movement:
      report of a case.

PMID- 20156670
TI  - Amino-functionalized single-chain bolalipids: synthesis and aggregation behavior
      of new basic building blocks.
AB  - Herein, we report the synthesis of two novel, amino-functionalized single-chain
      bolalipids and, based on those, a general synthetic approach for the insertion of
      various carboxylic acids into the bolalipid headgroups, e.g. alpha-lipoic acid
      for one-dimensional fixation of gold nanoparticles, sorbic acid for
      polymerization experiments, or lysine for the use in gene delivery systems. The
      temperature- and pH-dependent self-assembly of amino-functionalized bolalipids
      into nanofibers and micelles was investigated by differential scanning
      calorimetry (DSC), transmission electron microscopy (TEM) and dynamic light
      scattering (DLS). Rheological measurements were used to describe the macroscopic
      behavior of the formed temperature switchable hydrogels that can be fine-tuned
      for drug delivery applications. We showed that the viscoelastic properties of the
      hydrogel strongly depend on ionic interactions between bolalipid headgroups as
      well as on the ability to form hydrogen bonds.

PMID- 20156671
TI  - Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon
      carcinomas and increases sensitivity of doxorubicin resistant murine leukemia
      cells.
AB  - The effect of the targeted cytotoxic somatostatin (SST) analog AN-162, consisting
      of doxorubicin (DOX) conjugated to SST carrier RC-121, was investigated on the
      growth of human colorectal cancer (CRC) cell lines HT-29, HCT-15, and HCT-116 and
      a DOX-resistant mouse leukemia cell line P388/R84. mRNA for SST-receptors and
      high affinity binding sites for SST were detected in all CRC cell lines and in
      P388/R84 cells. In contrast to DOX alone, AN-162 blocked HCT-116 cells and
      P388/R84 cells in S/G2 phase and increased the number of apoptotic cells. In
      vivo, AN-162 reduced the volume of CRC xenografts more effectively than its
      unconjugated components. Our results suggest that AN-162 inhibits growth of
      experimental CRC more effectively than DOX and increases sensitivity of DOX
      resistant human leukemia cells.

PMID- 20156672
TI  - Surgical management of non-small cell lung cancer with mediastinal
      lymphadenopathy.
AB  - Several issues regarding the surgical management of N2 disease remain unresolved.
      First, the anatomical attribution of a mediastinal nodal station, especially in
      certain areas (i.e., azygos recess), is a source of continuous debate. Second,
      the presence of occult N2, single or multilevel N2, bulky N2, the skip phenomenon
      and the observation of a different prognostic outlook for specific mediastinal
      nodal stations are all elements of discussion that cannot clarify whether stage
      IIIA-N2 non-small cell lung cancer is indeed a locally, albeit advanced,
      manifestation of the disease or the prodrome of an actual systemic dissemination.
      In this subset of patients lies the challenge for multidisciplinary treatment
      modalities, where the surgical role needs to be further defined in the context of
      an integrated collaborative effort with the medical oncologist and the
      radiotherapist.

PMID- 20156673
TI  - Composition and production rate of medical waste from a small producer in Greece.
AB  - The objective of this work was to determine the composition and production rate
      of medical waste from the health care facility of social insurance institute, a
      small waste producer in Xanthi, Greece. Specifically, produced medical waste from
      the clinical pathology (medical microbiology) laboratory, the X-ray laboratory
      and the surgery and injection therapy departments of the health facility was
      monitored for six working weeks. A total of 240 kg medical solid waste was
      manually separated and weighed and 330 L of liquid medical waste was measured and
      classified. The hazardous waste fraction (%w/w) of the medical solid waste was
      91.6% for the clinical pathology laboratory, 12.9% for the X-ray laboratory,
      24.2% for the surgery departments and 17.6% for the injection therapy department.
      The infectious waste fraction (%w/w) of the hazardous medical solid waste was
      75.6% for the clinical pathology laboratory, 0% for the X-ray laboratory, 100%
      for the surgery departments and 75.6% for the injection therapy department. The
      total hazardous medical solid waste production rate was 64+/-15 g/patient/d for
      the clinical pathology laboratory, 7.2+/-1.6 g/patient/d for the X-ray
      laboratory, 8.3+/-5.1 g/patient/d for the surgery departments and 24+/-9
      g/patient/d for the injection therapy department. Liquid waste was produced by
      the clinical pathology laboratory (infectious-and-toxic) and the X-ray laboratory
      (toxic). The production rate for the clinical pathology laboratory was 0.03+/
      0.003 L/patient/d and for the X-ray laboratory was 0.06+/-0.006 L/patient/d. Due
      to the small amount produced, it was suggested that the most suitable management
      scheme would be to transport the hazardous medical waste, after source
      separation, to the Prefectural Hospital of Xanthi to be treated with the hospital
      waste. Assuming this data is representative of other small medical facilities,
      medical waste production can be estimated for such facilities distributed around
      Greece.

PMID- 20156674
TI  - Treating triple-negative breast cancer by a combination of rapamycin and
      cyclophosphamide: an in vivo bioluminescence imaging study.
AB  - Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to
      inhibit the growth of oestrogen positive breast cancer. However, triple-negative
      (TN) breast cancer is resistant to rapamycin treatment in vitro. We set to test a
      combination treatment of rapamycin with DNA-damage agent, cyclophosphamide, in a
      TN breast cancer model. By binding to and disrupting cellular DNA,
      cyclophosphamide kills cells via interfering with their normal functions. We
      assessed the responses of nude mice bearing tumour xenografts of TN MDA-MB-231
      cells to the combination of rapamycin and cyclophosphamide in both orthotopic
      mammary and lung-metastasis models. We tracked tumour growth and metastasis by
      bioluminescent imaging and examined the expression of Ki67, CD34 and HIF-1alpha
      in tumour tissues by immunohistochemistry and apoptosis index with TUNEL assay,
      and found that MDA-MB-231 cells are sensitive to rapamycin therapy in orthotopic
      mammary, but not in lung with metastasis. Rapamycin when combined with
      cyclophosphamide is found to have a more significant effect in reducing tumour
      volume and metastasis with a much improved survival rate. Our data also show that
      the sensitivity of TN tumours to rapamycin is associated with the
      microenvironment of the tumour cells. The data indicate that in a relatively
      hypoxic environment HIF-1alpha may play a role in mediating the anti-cancer
      effect of rapamycin and cyclophosphamide may prevent the feedback activation of
      Akt by rapamycin. Overall our results show that rapamycin plus cyclophosphamide
      can achieve an improved efficacy in suppressing tumour growth and metastasis,
      suggesting that the combination therapy can be a promising treatment option for
      TN cancer.

PMID- 20156676
TI  - Volatile organic acid adsorption and cation dissociation by porphyritic andesite
      for enhancing hydrolysis and acidogenesis of solid food wastes.
AB  - Volatile organic acid adsorption, cation dissociation by porphyritic andesite,
      and their effects on the hydrolysis and acidogenesis of solid food wastes were
      evaluated through batch experiments. The acetic acid adsorption experiments show
      that pH was mainly regulated by H(+) adsorption. The mono-layer and multi-layer
      adsorption were found under the low (8.3-83.2 mmol/L) and high (133.22-532.89
      mmol/L) initial acetic acid concentration, respectively. The dissociated cations
      concentration in acidic solution showed the predominance of Ca(2+). Porphyritic
      andesite addition elevated the pH levels and accelerated hydrolysis and
      acidogenesis in the batch fermentation experiment. Leachate of porphyritic
      andesite addition achieved the highest hydrolysis constant of 22.1 x 10(-3)kgm(
      2)d(-1) and VS degradation rates of 3.9 g L(-1)d(-1). The highest activity of
      microorganisms represented by specific growth rate of ATP, 0.16d(-1), and
      specific consumption rate of Ca(2+), 0.18d(-1), was obtained by adding leachate
      of porphyritic andesite.

PMID- 20156675
TI  - MDM2 inhibitor MI-319 in combination with cisplatin is an effective treatment for
      pancreatic cancer independent of p53 function.
AB  - Small molecule inhibitors (SMIs) of murine double minute 2 (MDM2) are known to
      restore the apoptotic and cell cycle regulatory functions of p53 by disrupting
      the MDM2-p53 interaction. In principle, these SMIs are not effective against
      tumours with mutation in the tumour suppressor p53 (mut-p53), which is known to
      be present in approximately 50% of all cancers. In this study we are reporting,
      for the first time, that MI-319 in combination with cisplatin induced cell growth
      inhibition and apoptosis in pancreatic cancer (PC) cells irrespective of their
      p53 mutational status. MI-319-cisplatin combination synergistically suppressed
      cell growth (MTT Combination Index [CI]<1) and colony formation (clonogenic
      assay) and induced apoptosis. Western blot analysis and siRNA silencing studies
      in mutant as well as p53 null cells highlighted a mechanism involving p73 which
      is also known to be under the regulation of MDM2, and unlike p53, it is rarely
      mutated in PC. Down-regulating MDM2 using siRNA enhanced p73 reactivation and
      increased cell death. Further, the combination effectively reduced tumour growth
      in both wt-p53 and mut-p53 tumour xenograft models (50% Capan-2 animals were
      tumour free). Consistent with our in vitro results, remnant tumour tissue
      analysis showed up-regulation of p73 and the cell cycle regulator p21. In
      conclusion, this study highlights a new role of MDM2 inhibitors in combination
      with cisplatin, and thus warrants further clinical investigation in human
      pancreatic tumours containing both wt-p53 and mut-p53.

PMID- 20156677
TI  - Optimization of removal conditions of copper ions from aqueous solutions by
      Trametes versicolor.
AB  - A multi-step response surface methodology was successfully applied to optimize
      the biosorption conditions for the maximum removal of Cu(II) ions from aqueous
      solutions using Trametes versicolor fungi as a biosorbent. In the first step, the
      most effective medium factors, which are pH, temperature and initial Cu(II)
      concentration, on biosorption of Cu(II), were determined through Plackett-Burman
      Design. Then steepest accent followed by central composite design steps were
      utilized to evaluate the optimum biosorption conditions for the maximum Cu(II)
      ions removal. Based on the statistic analysis; the optimum conditions were
      obtained 5.51, 20.13 degrees C and 60.98 mg/L as medium pH, medium temperature
      and initial Cu(II) concentration, respectively. Finally the analysis of variance
      (ANOVA) of central composite design showed the proposed quadratic model fitted
      experimental data very well.

PMID- 20156678
TI  - Effect of lime pre-treatment on the synergistic hydrolysis of sugarcane bagasse
      by hemicellulases.
AB  - Agricultural crop wastes are typically lignocellulosic in composition and thus
      partially recalcitrant to enzymatic degradation. The recalcitrant nature of plant
      biomass and the inability to obtain complete enzymatic hydrolysis has led to the
      establishment of various pre-treatment strategies. Alkaline pre-treatments
      increase the accessibility of the exposed surface to enzymatic hydrolysis through
      the removal of acetyl and uronic acid substituents on hemicelluloses. Unlike the
      use of steam and acid pre-treatments, alkaline pre-treatments (e.g. lime)
      solubilise lignin and a small percentage of the hemicelluloses. The most common
      alkaline pre-treatments that are employed make use of sodium hydroxide and lime.
      This study compared the synergistic degradation of un-treated and lime pre
      treated sugarcane bagasse using cellulosomal and non-cellulosomal hemicellulases
      as free enzymes. The enzyme combination of 37.5% ArfA and 62.5% ManA produced the
      highest amount of reducing sugar of 91.834 micromol/min for the degradation of un
      treated bagasse. This enzyme combination produced a degree of synergy of 1.87.
      The free enzymes displayed an approximately 6-fold increase in the enzyme
      activity, i.e. the total amount of reducing sugar released (593.65 micromol/min)
      with the enzyme combination of 37.5% ArfA, 25% ManA and 37.5% XynA for the lime
      pre-treated substrate and a degree of synergy of 2.14. To conclude, this study
      indicated that pre-treating the sugarcane bagasse is essential, in order to
      increase the efficiency of lignocellulose enzymatic hydrolysis by disruption of
      the lignin sheath, that the lime pre-treatment did not have any dramatic effect
      on the synergistic relationship between the free enzymes, and that time may play
      an important role in the establishment of synergistic relationships between
      enzymes.

PMID- 20156679
TI  - Hexavalent chromium adsorption on impregnated palm shell activated carbon with
      polyethyleneimine.
AB  - Removal of Cr(VI) ions from aqueous solution was investigated using modified palm
      shell activated carbon. Low Molecular Weight Polyethyleneimine (LMW PEI) was used
      for impregnation purpose. The maximum amount of LMW PEI adsorbed on activated
      carbon was determined to be approximately 228.2mg/g carbon. The adsorption
      experiments were carried out in a batch system using potassium dichromate
      K(2)Cr(2)O(7) as the source of Cr(VI) in the synthetic waste water and modified
      palm shell activated carbon as the adsorbent. The effects of pH, concentration of
      Cr(VI) and PEI loaded on activated carbon were studied. The adsorption data were
      found to fit well with the Freundlich isotherm model. This modified Palm shell
      activated carbon showed high adsorption capacity for chromium ions.

PMID- 20156680
TI  - Influence and optimization of growth substrates on indigo formation by a novel
      isolate Acinetobacter sp. PP-2.
AB  - In this study, a novel indigo-producing bacterial strain PP-2 was isolated from
      activated sludge. It was identified as Acinetobacter sp. according to
      phylogenetic similarity of 16S rRNA gene sequence. This isolate was able to
      produce indigo from indole by utilizing a wide range of aromatic hydrocarbons.
      The results of SDS-PAGE analysis showed that the enzyme system induced by phenol
      was more abundant than that induced by other aromatic hydrocarbons. And the
      effects of metal ions on indigo production were also investigated, which
      indicated that the activity of cells induced with phenol could be inhibited by
      0.5mM Fe(3+). Response surface methodology (RSM) was applied to optimize the
      process of indigo bio-production. The results exhibited that the maximal yield
      was achieved with 157.92 mg L(-1) phenol and 205.32 mg L(-1) indole. Under the
      optimal conditions, the indigo yield and transformation efficiency of indole were
      202.92 mg L(-1) and 88%, respectively.

PMID- 20156681
TI  - Effectiveness of acid-treated agricultural stones used in biopurification systems
      to avoid pesticide contamination of water resources caused by direct losses: part
      I. Equilibrium experiments and kinetics.
AB  - Several recent publications report the use of low-cost and locally available
      adsorbents in biopurification systems to eliminate pesticides from water.
      Nonetheless, the literature is insufficient to cover this problem, and more
      investigations are needed in this field to evaluate the possible application of
      economical adsorbents to prevent pesticide water resources contamination caused
      by direct losses. This study focuses on the fate of endosulfan metabolites, in
      small-scale biopurification systems, using as adsorbents treated and untreated
      organic agricultural stones (date, olive and avocado). The effects of sorbent
      particle size, adsorbent dose, contact time, concentration of pesticide solution
      and temperature on the adsorption processes were systematically studied in batch
      experiments. Pesticide determination was carried out using stir bar sorptive
      extraction and gas chromatography coupled with mass spectroscopy. Maximum removal
      efficiency (94.8%) was reached for endosulfan sulfate (0.1 mg L(-1)) using the
      acid-treated date stones (ATOS) fraction <125 microm (solid/liquid ratio: 1 g L(
      1)). According to the general behavior of the adsorption mechanism, date stones
      show the higher removal efficiency followed by olive and avocado stones,
      respectively. The analyses of the results reveal that the thermo chemical
      treatment improves notably the pesticides adsorption efficiency of the studied
      sorbents and that the adsorption decreases when the pesticide solubility rises.
      Experimental adsorption data were analyzed according to various kinetic models.
      Lagergren and Morris-Weber equations were applied to fit the kinetic results. The
      second order model was the most suitable and intra-particle diffusion was found
      to be the rate controlling the adsorption process.

PMID- 20156682
TI  - Assessment upon azo dye decolorization and bioelectricity generation by Proteus
      hauseri.
AB  - This study explored dye decolorization and bioelectricity generation of
      indigenous Proteus hauseri ZMd44 for dye-bearing wastewater treatment. Chemical
      structures of azo dyes apparently affected the performance of dye
      biodecolorization. Additions of diazo dye C.I. reactive blue 160 (RBu160)
      stimulated simultaneous dye decolorization and bioelectricity generation of ZMd44
      in single chamber microbial fuel cells (MFCs). However, high-level additions of
      RBu160 repressed capabilities of power production in MFC due to competition of
      electrons used for reductive decolorization. Decolorized intermediates of RBu160
      phenyl methadiamine and 5-sulfoanthranilic acid as electron shuttles might
      mediate electron transport for current generation in MFC.

PMID- 20156683
TI  - Modeling the kinetics of calcium hydroxide catalyzed methanolysis of sunflower
      oil.
AB  - The kinetics of Ca(OH)(2)-catalyzed methanolysis of sunflower oil was studied at
      a moderate temperature (60 degrees C), a methanol-to-oil molar ratio (6:1) and
      different catalyst amounts (from 1% to 10% based on oil weight). The methanolysis
      process was shown to involve the initial triglyceride (TG) mass transfer
      controlled region, followed by the chemical reaction controlled region in the
      latter period. The TG mass transfer limitation was caused by the low available
      active specific catalyst surface due to the high adsorbed methanol concentration.
      Both the TG mass transfer and chemical reaction rates increased with increasing
      the catalyst amount.

PMID- 20156684
TI  - Structural characteristics and antioxidant activities of the extracellular
      polysaccharides produced by marine bacterium Edwardsiella tarda.
AB  - Two water-soluble extracellular polysaccharides, ETW1 and ETW2, were isolated
      from the marine bacterium Edwardsiella tarda by ion-exchange and size-exclusion
      chromatography, and their structures were investigated. ETW1 and ETW2 are
      mannans, with molecular weights of about 29 and 70kDa, respectively. The main
      chain of the polysaccharides consists of (1-->3)-linked mannose residues, and
      branched mannose linkages were also detected. The branch points are located at
      the C-2 and C-6 positions of the (1-->3)-linked mannose residues. The side chains
      are composed of (1-->2)-linked mannose residues and (1-->)-linked mannose
      residues. Antioxidant properties of the two extracellular polysaccharides were
      evaluated with hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals
      scavenging activities and lipid peroxidation inhibition in vitro, and results
      showed that ETW1 and ETW2 had good antioxidant and hydroxyl and DPPH radicals
      scavenging activities. ETW1 exhibited higher antioxidant activity than ETW2, and
      could be a potential source of antioxidant and used as possible food supplement
      or ingredient in the pharmaceutical industry.

PMID- 20156685
TI  - Evaluation of performance and community dynamics of microorganisms during
      treatment of distillery spent wash in a three stage bioreactor.
AB  - The ability of Emericella nidulans var. lata, Neurospora intermedia and Bacillus
      sp. to treat distillery spent wash in a three stage bioreactor was investigated.
      Process parameters were optimized in shake flask cultures with the individual
      strains before treatment of the effluent in a 15-l bioreactor. Treatment was
      first carried out by the fungi followed by bacteria. The treated effluent showed
      significant reduction in color (82%) and COD (93%) after 30 h. Metabolites formed
      after degradation of complex polymers in distillery effluent were assayed by gas
      chromatography-mass spectroscopy and included furan, simple acid types and
      organic compounds. Denaturing gradient gel electrophoresis of 16S rDNA and 18S
      rDNA sequences amplified from DNA isolated from the reactor communities indicated
      the presence of other organisms besides those introduced initially. The microbial
      communities were able to carry out bioremediation of distillery effluent and
      produce discharge that conforms to safety standards.

PMID- 20156686
TI  - Pretreatment of wheat straw by nonionic surfactant-assisted dilute acid for
      enhancing enzymatic hydrolysis and ethanol production.
AB  - Pretreating wheat straw (WS) with combined use of varied sulfuric acid
      concentration (0-3%, w/v) and Tween 20 concentration (0-1%) was investigated in
      an attempt to enhance the hydrolysis and fermentability of pretreated WS.
      Enzymatic hydrolysis yield of glucan and xylan and ethanol production by
      simultaneous saccharification and fermentation (SSF) of water-insoluble solids
      (WIS) were significantly affected by the amount of Tween 20 added during acid
      pretreatment. Any further addition of Tween 20 in either hydrolysis stage or
      fermentation stage only led to small increase in glucan conversion and ethanol
      production. Determination of adsorption of cellulases during hydrolysis showed
      that Tween 20-assisted acid treated straw solution contained more free cellulases
      than individual acid treated straw solution, indicating that modification of
      lignin surface by Tween 20 added during pretreatment likely occurred. In
      addition, the effects of pretreatment conditions on overall recovery of glucose
      and xylose after pretreatment and enzymatic hydrolysis were also investigated.

PMID- 20156688
TI  - Papillary glioneuronal tumor of the frontal lobe.
AB  - Glioneuronal tumors of the central nervous system (CNS) comprise a group of
      generally low-grade tumors expressing glial and neuronal cells of varying
      differentiation. Papillary glioneuronal tumor (PGNT) is a new tumor identified in
      the World Health Organization's classification of CNS tumors (2007). We report a
      patient with PGNT and highlight the diagnostic features, including a description
      of "spidery" astrocytes.

PMID- 20156687
TI  - Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric
      modulator (PAM) lead. Part II: development of a potent and highly selective M1
      PAM.
AB  - This Letter describes a chemical lead optimization campaign directed at
      VU0119498, a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM)
      with the goal of developing a selective M(1) PAM. An iterative library synthesis
      approach delivered a potent (M(1) EC(50)=830 nM) and highly selective M(1) PAM
      (>30 microM vs M(2)-M(5)).

PMID- 20156689
TI  - Colony stimulating factor-1 receptor as a target for small molecule inhibitors.
AB  - Imatinib, dasatinib, sunitinib, CEP-701, and PKC-412, ATP-competitive small
      molecule inhibitors of type III receptor tyrosine kinases c-KIT and/or FLT3, were
      evaluated for binding to the closely related receptor, FMS, by docking into
      models of inactive and active conformations of the FMS kinase domain. To confirm
      the docking predictions, the drugs were tested for their activity and selectivity
      in inhibiting cell proliferation and FMS phosphorylation upon stimulation by the
      FMS ligand, CSF-1. All five drugs inhibited FMS activity. Imatinib, dasatinib and
      CEP-701 represent three different types of interactions determining drug potency
      and selectivity.

PMID- 20156690
TI  - Exploring a synthetic organoselenium compound for antioxidant pharmacotherapy-
      toxicity and effects on ROS-production.
AB  - The organoselenium antioxidant 1 was previously found to act as a catalytic
      antioxidant in a two-phase lipid peroxidation system. In aqueous environment,
      selenide 1 quenched ABTS-radicals more efficiently than Trolox and ascorbic acid.
      The selenide dose-dependently scavenged reactive oxygen and nitrogen species more
      efficiently than Trolox for neutrophils and PMA-stimulated macrophages, with 50%
      inhibitory concentrations in the low micromolar range. In addition no sign of
      toxicity or effect on cell viability was seen when culturing five human cell
      lines in concentrations up to 200 microM of selenide 1 for up to seven days. We
      therefore feel that the compound would be a good candidate for future drug
      development for prevention or treatment of disorders caused by or involving free
      radical-mediated or oxidative tissue damage.

PMID- 20156691
TI  - Transcriptional regulation of the rice arginine decarboxylase (Adc1) and S
      adenosylmethionine decarboxylase (Samdc) genes by methyl jasmonate.
AB  - We investigated the effect of methyl jasmonate (MeJa) treatment on the expression
      of two genes in the rice polyamine biosynthesis pathway and on the polyamine
      content in wild type plants and transgenic rice plants expressing a Datura
      stramonium (Ds) Adc cDNA, the latter accumulating up to three-fold the normal
      level of putrescine. Exogenous MeJa transiently inhibited the expression of
      OsAdc1, OsSamdc and Spermidine synthase (OsSpds) genes in the polyamine
      biosynthesis pathway, probably through transcriptional repression. There was also
      a similar negative impact on the DsAdc transgene in transgenic plants, even
      though a constitutive promoter was used to drive transgene expression. The free
      putrescine content was reduced significantly in the leaves of both wild type and
      transgenic plants in response to MeJa, although the magnitude of the effect was
      greater in wild type plants. We discuss our findings with respect to the
      previously proposed threshold model of polyamine metabolism in plants subjected
      to abiotic stress.

PMID- 20156692
TI  - Clinical aspects of a 2.0-mm locking plate system for mandibular fracture
      surgery.
AB  - PURPOSE: The use of a 2.0-mm locking plate system was evaluated in mandibular
      surgery. PATIENTS AND METHODS: 53 patients (42 male, 11 female) with a total of
      56 mandibular fractures were treated with a 2.0-mm mini-locking-plate system and
      retrospectively examined. Gender, age, cause of fracture, surgical access,
      classification of fractures, osteosynthesis, postsurgical findings and
      complications were evaluated. RESULTS: Assault in male patients (mean age 31) was
      the most common aetiological factor. Fractures in women (mean age 43 years)
      mostly occurred due to falls. Mandibular angle fractures were the most common and
      this anatomical site also presented the highest complication rate. Only 6% of
      patients had minor occlusal disturbance postoperatively, and minor complications
      (infections and dehiscence) occurred in 14% of patients in this study. Major
      complications only occurred in one patient included in the study (1.9%). Risk
      factors for the development of complications in this series were a history of
      alcohol or tobacco use, mandibular angle fractures, associated facial fractures,
      presurgical occlusal disturbance and concomitant dental infections. Surgical
      access to the fracture and the interval from injury to surgery was not associated
      with the development of complications. CONCLUSIONS: The use of a 2.0-mm locking
      plate system with its advantages of improved handling characteristics, increased
      stability, shorter surgical time and the preservation of bony perfusion is a
      viable alternative to conventional miniplates in the management of mandibular
      fractures.

PMID- 20156693
TI  - The role of anticipatory postural adjustments in compensatory control of posture:
      2. Biomechanical analysis.
AB  - The central nervous system (CNS) utilizes anticipatory (APAs) and compensatory
      (CPAs) postural adjustments to maintain equilibrium while standing. It is known
      that these postural adjustments involve displacements of the center of mass (COM)
      and center of pressure (COP). The purpose of the study was to investigate the
      relationship between APAs and CPAs from a kinetic and kinematic perspective.
      Eight subjects were exposed to external predictable and unpredictable
      perturbations induced at the shoulder level while standing. Kinematic and kinetic
      data were recorded and analyzed during the time duration typical for anticipatory
      and compensatory postural adjustments. When the perturbations were unpredictable,
      the COM and COP displacements were larger compared to predictable conditions with
      APAs. Thus, the peak of COM displacement, after the pendulum impact, in the
      posterior direction reached 28+/-9.6mm in the unpredictable conditions with no
      APAs whereas it was 1.6 times smaller, reaching 17+/-5.5mm during predictable
      perturbations. Similarly, after the impact, the peak of COP displacement in the
      posterior direction was 60+/-14 mm for unpredictable conditions and 28+/-3.6mm
      for predictable conditions. Finally, the times of the peak COM and COP
      displacements were similar in the predictable and unpredictable conditions. This
      outcome provides additional knowledge about how body balance is controlled in
      presence and in absence of information about the forthcoming perturbation.
      Moreover, it suggests that control of posture could be enhanced by better
      utilization of APAs and such an approach could be considered as a valuable
      modality in the rehabilitation of individuals with balance impairment.

PMID- 20156694
TI  - Oropharyngeal candidiasis in the era of antiretroviral therapy.
AB  - Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected
      population despite the availability of antiretroviral therapy (ART). Although
      Candida albicans is the most frequently implicated pathogen, other Candida
      species also may cause infection. The emergence of antifungal resistance within
      these causative yeasts, especially in patients with recurrent oropharyngeal
      infection or with long-term use of antifungal therapies, requires a working
      knowledge of alternative antifungal agents. Identification of the infecting
      organism and antifungal susceptibility testing enhances the ability of clinicians
      to prescribe appropriate antifungal therapy. Characterization of the responsible
      mechanisms has improved our understanding of the development of antifungal
      resistance and could enhance the management of these infections. Immune
      reconstitution has been shown to reduce rates of OPC, but few studies have
      evaluated the current impact of ART on the epidemiology of OPC and antifungal
      resistance in these patients. Preliminary results from an ongoing clinical study
      showed that in patients with advanced AIDS, oral yeast colonization was
      extensive, occurring in 81.1% of the 122 patients studied, and symptomatic
      infection occurred in one-third. In addition, resistant yeasts were still common,
      occurring in 25.3% of patients colonized with yeasts or with symptomatic
      infection. Thus, OPC remains a significant infection in advanced AIDS, even with
      ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation,
      treatment, and mechanisms of antifungal resistance observed in OPC are important
      in managing patients with this infection and are the focus of this review.

PMID- 20156695
TI  - Functional endoscopic sinus surgery as an adjunctive treatment for closure of
      oroantral fistulae: a retrospective analysis.
AB  - OBJECTIVE: The objective of this study was to report results of functional
      endoscopic sinus surgery (FESS) for treatment of chronic maxillary sinusitis of
      dental origin in a series of patients with oroantral fistulae (OAF). STUDY
      DESIGN: Fourteen patients were treated by FESS and OAF closure by local flap.
      Data on severity of symptoms, diagnostic endoscopy, and coronal CT scan findings,
      as well as intraoperative course and complications, were recorded. The follow-up
      period lasted up to 2 years, comprising clinical examinations and control CT
      scans. RESULTS: All OAF healed uneventfully. All patients reported improvement in
      severity of sinusitis symptoms, which was confirmed through results of clinical
      examinations and control CT scans. No significant complications were recorded. No
      revision surgery was needed in any case. CONCLUSION: These results indicate that
      FESS, combined with OAF closure by buccal flap, might be an effective and safe
      option for treatment of selected cases of chronic odontogenic sinusitis with OAF.

PMID- 20156696
TI  - Liver, liver cell and stem cell transplantation for the treatment of urea cycle
      defects.
AB  - Despite advances in pharmacological therapy of urea cycle disorders (UCDs), the
      overall long-term prognosis is poor, especially for neonatal manifestations.
      Transplantation of liver tissue or isolated cells appears suitable for transfer
      of the missing enzyme. Liver transplantation (LT) for UCDs has an excellent 5
      year survival rate of approximately 90% and is the only way to completely cure
      the disease. However, major neurological damage can only be prevented if the
      operation is performed during the first months of life. Unfortunately, such early
      LTs have a substantial risk for peri- and postoperative complications, mostly
      caused by a relatively large liver graft. Liver cell transplantation (LCT) is
      less invasive than LT, but has still to be regarded as an experimental therapy
      with about 100 patients treated since its first use in 1993. UCDs are a model
      disease for LCT, because of the poor prognosis, mainly hepatic enzyme defects,
      and excellent outcome after LT. So far, 10 children underwent LCT for UCDs with
      very few technical complications and encouraging clinical results. A first
      prospective study on its use in severe neonatal UCDs has recently started.
      However, availability of hepatocytes is limited by the scarcity of donor livers;
      therefore the use of stem cells is under investigation. Several different cell
      types may be regarded as liver stem cells, and in vivo transformation into
      hepatocyte-like cells has been shown in animal studies. However, a clear proof of
      principle in animal models of human metabolic disease is still missing, which is
      the prerequisite for clinical application in humans.

PMID- 20156697
TI  - A common mutation, R208X, identified in Vietnamese patients with mitochondrial
      acetoacetyl-CoA thiolase (T2) deficiency.
AB  - Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is an inborn error of
      metabolism affecting isoleucine catabolism and ketone body utilization. This
      disorder is clinically characterized by intermittent ketoacidotic episodes with
      no clinical symptoms between episodes. In general, T2 gene mutations are
      heterogeneous. No common mutations have been identified and more than 70
      mutations have been identified in 70 patients with T2 deficiency (including
      unpublished data). We herein identified a common mutation, R208X, in Vietnamese
      patients. We identified R208X homozygously in six patients and heterozygously in
      two patients among eight Vietnamese patients. This R208X mutation was also
      identified heterozygously in two Dutch patients, however, R208X mutant alleles in
      the Vietnamese have a different haplotype from that in the Dutch, when analyzed
      using Msp I and Taq I polymorphisms in the T2 gene. The R208X mutant allele was
      not so frequent in the Vietnamese since we could not find that mutant allele in
      400 healthy Vietnamese controls using the Nla III restriction enzyme assay. DNA
      diagnosis of T2 deficiency may be applicable to the Vietnamese population.

PMID- 20156698
TI  - Cutaneous mycoflora and CD4:CD8 ratio of cats infected with feline
      immunodeficiency virus.
AB  - This study was designed to compare cutaneous mycoflora isolation and CD4+:CD8+
      ratio in feline immunodeficiency virus (FIV)-infected cats with that in FIV
      uninfected cats. Sixty cats were examined. Twenty-five were FIV-infected cats and
      35 were FIV-uninfected cats. All 60 cats were FeLV-negative. Fungi were speciated
      and immunophenotyping of peripheral CD4+ and CD8+ T lymphocytes was performed. At
      least one fungal colony was isolated from 22/25 (88%) FIV-infected cats. Among
      the FIV-uninfected cats fungal colonies were recovered from 13/35 (37%)
      specimens. Dermatophytes were recovered from 2/25 (8%) FIV-infected cats (one
      Microsporum gypseum, one Microsporum canis) and 3/35 (8.5%) FIV-uninfected cats
      (M gypseum). Malassezia species was the most commonly isolated organism from both
      groups of cats (51.6%). Malassezia species was more commonly isolated from FIV
      infected cats than FIV-uninfected cats (84% vs 28.6%). The CD4+ to CD8+
      lymphocyte ratio for FIV-infected cats was significantly lower than the CD4+ to
      CD8+ ratio in the FIV-uninfected cats. The CD4+ to CD8+ lymphocyte ratio for FIV
      infected cats with cutaneous overall fungal isolation was significantly lower
      than the CD4:CD8 lymphocyte ratio in the FIV-infected cats but without cutaneous
      fungal isolation. We can conclude that immunologic depletion due to retroviral
      infection might represent a risk factor to cutaneous fungal colonization in cats.

PMID- 20156699
TI  - Evaluation of the anti-endotoxin effects of polymyxin B in a feline model of
      endotoxemia.
AB  - Directed, effective therapies for feline sepsis are needed to reduce the high
      morbidity and mortality associated with this disease. We investigated the anti
      endotoxin effects of polymyxin B (PMB) in a blinded, placebo controlled fashion,
      both ex vivo in a feline whole blood culture system and in vivo, using a low-dose
      endotoxin infusion in cats. Serial measures of systemic inflammation, and
      hemodynamic stability, were compared between groups. Ex vivo, PMB significantly
      decreased lipopolysaccharide-induced tumor necrosis factor (TNF) production from
      whole blood. PMB (1mg/kg over 30min) demonstrated anti-endotoxin effects in vivo,
      including decreased peak plasma TNF activity (P<0.001) and increased white blood
      cell count (P=0.019), with no adverse effects. Given the apparent safety and anti
      endotoxin effects of PMB in this endotoxemia model, a carefully designed,
      randomized, blinded, placebo controlled clinical trial evaluating the use of PMB
      in naturally occurring Gram-negative feline sepsis should be considered.

PMID- 20156700
TI  - Tapered dose versus constant drug exposure to anti-EGFR drugs on head-and-neck
      cancer xenografts. A comparison between cetuximab and gefitinib.
AB  - Head-and-neck (H&N) tumor re-growth is clinically observed after arrest of anti
      EGFR therapies. In the present study, we compared, for a similar dose exposure to
      anti-EGFR therapies, constant (CS) with tapered (TS) schedules (i.e. progressive
      dose reduction) for cetuximab, a mAb, and gefitinib, a TKI. Mice bearing CAL33
      H&N tumors with high EGFR content were treated with cetuximab or gefitinib. CS
      consisted of 7 days of cetuximab or gefitinib administration and TS of 7 days of
      drugs followed by 7 days of administration at decreased doses (divided by 2 every
      day). Gefitinib TS but not CS slowed down tumor re-growth. Cetuximab TS had a
      stronger and longer-lasting effect than CS, paralleled by a down-regulation of
      EGFR expression. Whatever the drug, TS decreased tumor re-growth more efficiently
      than CS. This new drug schedule could be of interest in the management of anti
      EGFR based therapies in H&N cancer.

PMID- 20156701
TI  - Sleep disorders in chronic kidney disease.

PMID- 20156702
TI  - Short sleep duration is associated with poor performance on IQ measures in
      healthy school-age children.
AB  - OBJECTIVE: To examine the associations between habitual sleep duration and
      intellectual functioning in healthy, well-rested, school-age children. METHODS:
      The study group consisted of 39 healthy children, aged 7-11 years old. Nightly
      actigraphic sleep recordings were taken for four consecutive nights to determine
      habitual week-night sleep duration in the home environment. Objective measures of
      cognitive functioning and sleepiness were used to measure daytime functioning.
      RESULTS: Longer habitual sleep duration in healthy school-age participants was
      associated with better performance on measures of perceptual reasoning and
      overall IQ, as measured by the WISC-IV, and on reported measures of competence
      and academic performance. No association between sleep duration and the studied
      behavioral measures was found. CONCLUSIONS: These findings support the hypothesis
      that sleep duration is differentially related to some components of cognitive
      functioning, even in the absence of evidence for sleep deprivation or attention
      deficits.

PMID- 20156703
TI  - Role of vascular endothelial growth factor in women with PCO and PCOS: a
      systematic review.
AB  - The aim of this study was to investigate the strategic role of vascular
      endothelial growth factor (VEGF) in the pathophysiology of polycystic ovary
      syndrome (PCOS) and to critically review the published trials that have evaluated
      VEGF in women with PCOS. An electronic database search of Medline, Embase, Cinahl
      and Cochrane library was conducted. Studies were included if they evaluated VEGF
      either in the circulation or in granulosa lutein cell culture media in in-vitro
      laboratory studies of women with a polycystic ovary (PCO) or PCOS. Studies
      analysing immunohistochemical expression of VEGF in PCO were also included. This
      review concluded that VEGF may have a strategic role in the pathophysiology of
      PCOS and is the key mediator in the pathogenesis of ovarian hyperstimulation
      syndrome (OHSS) in women undergoing assisted reproductive procedures. Its role is
      perhaps not singular and several other factors such as the bioavailability of its
      soluble receptor sFlt-1 and a multidisciplinary orchestration of other cytokines
      and growth factors may be involved in the pathophysiology of PCOS and OHSS.

PMID- 20156704
TI  - Biosignificance of bacterial cyanogenesis in the CF lung.
AB  - Two recent studies have demonstrated the presence of biologically significant
      amounts of cyanide within the airways of cystic fibrosis (CF) patients infected
      with Pseudomonas aeruginosa. Whilst environmental strains of P. aeruginosa are
      known to synthesise cyanide, there has been a relative lack of investigation into
      bacterial cyanogenesis from a medical viewpoint, despite the role P. aeruginosa
      plays in many serious infection settings and especially in CF lung disease. This
      review discusses the implications of cyanogenesis in the CF airway in terms of
      bacterial ecology, host immune response, progression of lung disease and
      potential treatment options.

PMID- 20156705
TI  - [Outcome of critically ill patients with acute renal failure and multiple organ
      failure treated with continuous venovenous haemodiafiltration].
AB  - OBJECTIVE: Acute renal failure (ARF) is associated to multiple organ failure
      (MOF) in critically ill patients and its mortality is high. The main objective
      was to evaluate the outcome of critically ill patients with ARF and MOF treated
      with continuous venovenous hemodiafiltration (CVVHDF). DESIGN: Retrospective and
      observational study on critically ill patients. SETTING: Medical-surgical
      Intensive Care Unit (ICU) in a University Hospital of Girona. PATIENTS: Patients
      admitted in ICU that developed ARF and MOF and were treated with CVVHDF. PRIMARY
      VARIABLES OF INTEREST: We collected data on demographic, and severity and organic
      dysfunction scores (SOFA). To study the risk factors for mortality, a comparative
      and multiple regression statistical analysis was performed, with the main effect
      of the study being mortality at 30 days. RESULTS: We studied 139 patients. The
      most frequent predisposing factors were hypotension (98%) and sepsis (82%). the
      most frequently affected organs were cardiocirculatory (94%) and respiratory
      (47%) associated to ARF. Mean SOFA score was 11.4 + or - 2.7 points. Survival was
      better in traumatic and in non-oliguric patients. The 30-day mortality was 61%
      and the logistic regression analysis showed that age > or = 60 years [OR=3.3 (95%
      CI 95=1.5-7.0)] and SOFA score > or = 11 points [OR=2.5 (95% CI=1.1-5.3)] were
      related to mortality. CONCLUSIONS: The mortality rate of critically ill patients
      with acute renal failure and multiple organ failure remains high. Traumatic and
      non-oliguric patients have a better survival. Age > or = 60 years and SOFA > or =
      11 points were independent risk factors associated with mortality.

PMID- 20156706
TI  - [Seasonal influence in characteristics of patients admitted to an intensive care
      unit].
AB  - OBJECTIVE: To investigate seasonal variability in the epidemiology and the
      outcome of critical illness. DESIGN: Retrospective analysis of prospectively
      collected data during the period 2001-2008. SETTING: Polyvalent intensive care
      unit (ICU) of a tertiary hospital in the Canary Islands. PATIENTS: Adult patients
      who were hospitalized in the ICU from the Emergency Department, according to the
      season period (spring, summer, autumn and winter). PRIMARY VARIABLES OF INTEREST:
      Demographic data, clinical diagnosis on ICU admission, APACHE II, need of
      mechanical ventilation and, finally, the mortality were collected. RESULTS:
      During the study period, 3,115 patients, coming from the Emergency Department,
      were hospitalized in our ICU. Of these, 21% were admitted during the summer, an
      incidence rate that is statistically lower than in other seasons of the year
      (P<0.001). We did not find any statistically significant differences between the
      four groups according to the age, type of patients, severity at the moment of
      admission to the ICU, according to the APACHE II score or in the mortality rate
      in the ICU. However, significant differences were found in regards to gender.
      Admission of women during the summer was higher than in winter (33% vs 27%,
      P=0.037). Average stay in the ICU of patients admitted in the summer was similar
      to winter (4.9 days vs 5.8 days; P=0.052). Need for mechanical ventilation and
      days it was required, by diagnostic groups, were similar between the summer and
      the winter. The multivariate analysis did not show independent variables
      associated with the seasonal period in which the patients were admitted.
      CONCLUSIONS: The stability of our climate implies that this factor does not
      influence the prognosis of patients who are admitted with critical illness.

PMID- 20156707
TI  - [Hyperoxia-induced pulmonary toxicity].
AB  - Mechanical ventilation may cause and aggravate lung damage and contribute to the
      appearance of multiorgan failure. One of the mechanisms that has been described
      is alveolar hyperoxia. In experimental models, it has lead to the production of
      free oxygen radicals that exceed the cell defense capacity, giving rise to
      inflammation, cell damage and gene overexpression with necrosis and apoptosis
      phenomenon. However, these findings in humans are not as conclusive, although a
      functional alteration due to the exposure to high FiO(2), and greater lung de
      recruitment in patients with lung injury has been clearly demonstrated. Moreover,
      both the FiO(2) used as well as the PaO(2) achieved in the first 24h of admission
      are associated with mortality. Clinical trials are needed that assess the
      threshold of the safe oxygen level for FiO(2) and oxygen saturation.

PMID- 20156708
TI  - [Transfusion-related acute lung injury].
AB  - The term Transfusion-Related Acute Lung Injury (TRALI) was coined in 1985. It is
      a relatively rare, life-threatening clinical syndrome characterized by acute
      respiratory failure and non-cardiogenic pulmonary edema during or following a
      blood transfusion. Although its true incidence is unknown, a rate 1 out of every
      5000 transfusions has been quoted. TRALI has been the most common cause of
      transfusion-related fatalities during three years in the USA. Two different
      etiologies have been proposed. The first is a single antibody-mediated event
      involving the transfusion of anti-HLA or antigranulocyte antibodies into patients
      whose leukocytes express the cognate antigens. The second is a two-event model:
      the first event is related to the clinical condition of the patient (sepsis,
      trauma, etc.) resulting in pulmonary endothelial activation and neutrophil
      sequestration, and the second event is the transfusion of a biologic response
      modifier that activates these adherent polymorphonuclear leukocytes resulting in
      endothelial damage and capillary leak. The patient management is support as
      needed based on the severity of the clinical picture and strategies to prevent
      TRALI are focused on: donor-exclusion policies, product management strategies and
      avoidance of unnecessary transfusions.

PMID- 20156710
TI  - [Managing knowledge in intensive medicine].

PMID- 20156709
TI  - [Herpes simplex virus bronchopneumonitis in patient with acute respiratory
      failure after surgery].
AB  - Herpes simplex virus bronchopneumonitis is a clinical entity described in
      critically ill patients and classically associated to immunosuppression. Recent
      reports have shown a higher frequency of virus detection from samples obtained by
      bronchoalveolar lavage of immunocompetent critically ill patients undergoing
      mechanical ventilation. This fact suggests its role as an independent pathogenic
      substrate. We report the case of a female patient who was admitted after an
      elective surgery of rectal tumor with suspected bronchoaspiration during
      anesthetic induction. The patient presented persistent fever despite broad
      spectrum antibiotic treatment. All cultures were negative for bacterial growth.
      The chest X-ray did not show opacifities. Prolonged mechanical ventilation with
      repeated failures to wean made it mandatory to perform percutaneous tracheostomy.
      A fibrobronchoscopy with bronchoalveolar lavage, performed previously, showed
      positive result for herpes simplex virus (PCR and specific nuclear inclusions in
      cells). Thus, treatment was initiated with acyclovir, with clinical improvement
      and weaning from mechanical ventilation.

PMID- 20156711
TI  - [Austrian syndrome].

PMID- 20156712
TI  - [Non-occlusive stent thrombosis associated to cardiocirculatory arrest].

PMID- 20156714
TI  - Cortical control of Hering-Breuer reflexes in anesthetized rats.
AB  - It had been hypothesized that the regions of prefrontal cortex which are involved
      in respiratory control can modulate Hering-Breuer reflexes evoked by vagal input
      from pulmonary stretch receptors. In the present study, experiments were
      performed on urethane anesthetized spontaneously breathing Wistar rats. The
      expiratory-promoting reflex was evaluated from changes in expiratory time
      immediately after airway occlusion at the end of inspiration. The inspiratory
      inhibitory reflex was estimated from changes in inspiratory time provoked by
      airway occlusion at the end of expiration. The results indicate that electrical
      microstimulation of the responsive sites within the insular cortex significantly
      weakened both expiratory-promoting and inspiratory-inhibitory reflex. Activation
      of the infralimbic cortex depressed expiratory-promoting reflex, but inspiratory
      inhibitory reflex was enhanced. These results suggest that stimulation of the
      prefrontal cortex influences vagally mediated control of the respiratory phases
      timing and several regions of the prefrontal cortex modulate distinct sets of
      neurons in the network controlling inspiratory and expiratory phases of a breath
      cycle.

PMID- 20156715
TI  - Exhaled nitric oxide - circadian variations in healthy subjects.
AB  - OBJECTIVE: Exhaled nitric oxide (eNO) has been suggested as a marker of airway
      inflammatory diseases. The level of eNO is influenced by many various factor
      including age, sex, menstrual cycle, exercise, food, drugs, etc. The aim of our
      study was to investigate a potential influence of circadian variation on eNO
      level in healthy subjects. METHODS: Measurements were performed in 44 women and
      10 men, non-smokers, without respiratory tract infection in last 2 weeks. The eNO
      was detected at 4-hour intervals from 6 a.m. to 10 p.m. using an NIOX analyzer.
      We followed the ATS/ERS guidelines for eNO measurement and analysis. RESULTS:
      Peak of eNO levels were observed at 10 a.m. (11.1 +/- 7.2 ppb), the lowest value
      was detected at 10 p.m. (10.0 +/- 5.8 ppb). The difference was statistically
      significant (paired t-test, P<0.001). CONCLUSIONS: The daily variations in eNO,
      with the peak in the morning hours, could be of importance in clinical practice
      regarding the choice of optimal time for monitoring eNO in patients with
      respiratory disease.

PMID- 20156716
TI  - Factors attributable to the level of exhaled nitric oxide in asthmatic children.
AB  - BACKGROUND: Asthma is a heterogeneous disease with variable symptoms especially
      in children. Exhaled nitric oxide (FeNO) has proved to be a marker of
      inflammation in the airways and has become a substantial part of clinical
      management of asthmatic children due to its potential to predict possible
      exacerbation and adjust the dose of inhalant corticosteroids. OBJECTIVES: We
      analyzed potential factors that contribute to the variability of nitric oxide in
      various clinical and laboratory conditions. MATERIAL AND METHODS: Study
      population consisted of 222 asthmatic children and 27 healthy control subjects.
      All children underwent a panel of tests: fractioned exhaled nitric oxide, exhaled
      carbon monoxide, asthma control test scoring, blood sampling, skin prick tests,
      and basic spirometry. RESULTS: FeNO and other investigated parameters widely
      changed according to clinical or laboratory characteristics of the tested
      children. Asthmatics showed increased levels of FeNO, exhaled carbon monoxide,
      total serum IgE, and higher eosinophilia. Boys had higher FeNO levels than girls.
      We found a significant positive correlation between FeNO levels and the
      percentage of blood eosinophils, %predicted of forced vital capacity, total serum
      IgE levels, and increasing age. CONCLUSIONS: Various phenotypes of children's
      asthma are characterized by specific pattern of the results of clinical and
      laboratory tests. FeNO correlates with total serum IgE, blood eosinophilia, age,
      and some spirometric parameters with different strength. Therefore, the
      coexistence of atopy, concomitant allergic rhinitis/rhinoconjunctivitis, and some
      other parameters should be considered in critical evaluation of FeNO in the
      management of asthmatic children.

PMID- 20156717
TI  - Lung function: occupational exposure to wood dust.
AB  - OBJECTIVES: Occupational exposure to wood dust has been shown to cause several
      respiratory disorders, such as allergic rhinitis, chronic bronchitis, asthma,
      sino-nasal adenocarcinoma, and impairment of lung function. The aim of the study
      was to estimate lung function (in the woodworking industry) among workers
      employed by wood processing, who run the risk of being expose to wood dust.
      METHODS: The study concerns a group of 70 workers aged 24- 55. All the workers
      underwent general and laryngological examination. A group of 20 workers, working
      at the positions where dustiness exceeded TLV (threshold limit value) took X-ray
      of the chest and spirometry. The following parameters were measured: VC, IC, ERV,
      TV, BF, FEV(1), FVC, PEF, MEF(25-75), FEV(1)%FVC, FEV(1)%VC. The data are
      presented as means +/- SD and the authors applied references values according to
      ERS guidelines. RESULTS: The results show that there was no decline in FEV(1)
      (3.7 +/- 0.7) and FVC (4.5 +/- 0.8). Normal lung function was defined as
      FEV(1)/VC ratio > or =0.7. None of the tested workers had obstructive pattern in
      spirometry. The mean FEV(1)%VC was 77.1 +/- 10.2. These results suggest that wood
      dust exposure might not lead to significant pulmonary damage. CONCLUSIONS: These
      data do not corroborate that wood dust plays significant role in lung function
      impairment. Future studies of respiratory health among workers exposed to wood
      dust are needed.

PMID- 20156718
TI  - Bidirectional link between upper and lower airways in patients with allergic
      rhinitis.
AB  - OBJECTIVE: Exhaled nitric oxide has been proposed as a noninvasive marker of
      eosinophilic airway inflammation in lower airways. The aim of the study was to
      investigate the impact of atopy, pollen exposure, and pharmacological treatment
      on NO production in lower airways of patients with allergic rhinitis. SUBJECTS
      AND METHODS: Measurements of exhaled NO were performed in 79 non-asthmatic
      subjects with seasonal allergic rhinitis outside and in pollen season, before and
      after pharmacological treatment, and in 54 healthy controls. RESULTS: Patients
      with allergic rhinitis had significantly higher levels of exhaled NO (18.3 +/
      11.0 ppb) than healthy controls (13.0 +/-7.2 ppb) measured outside the pollen
      season (P=;0.0024). Increased exhaled NO levels were also found in patients with
      allergic rhinitis in the pollen season (27.0 +/-20.0 ppb) compared with the
      levels outside pollen season (P=0.0001), before pharmacological treatment. In
      rhinitic patients treated by nasal corticosteroids and antihistamines in the
      pollen season, the levels of exhaled NO were significantly lower (17.0 +/-16.4
      ppb; P=0.045) than those before treatment. No difference was found in NO levels
      in rhinitic patients outside and in pollen season after pharmacological
      treatment. CONCLUSIONS: This study has shown the presence of eosinophilic airway
      inflammation in the lower airways in allergic rhinitis patients. A significant
      increase of exhaled NO after pollen exposure in rhinitic patients underlies the
      impact of inflammation on the upper respiratory tract. A bidirectional link
      between upper and lower airways is confirmed by a decrease in exhaled NO in the
      pollen season, almost to the starting levels, after application of topic
      corticosteroids and antihistamines.

PMID- 20156719
TI  - Influence of smoking and body weight on adipokines in middle aged women.
AB  - OBJECTIVE: Quitting smoking was associated with an undesirable weight gain. Both,
      cigarette smoking and obesity were accompanied by subclinical systemic
      inflammation. This may cause unfavourable changes in (plasma) adipokine
      concentration. The aim of the present study was to establish the influence of
      moderate cigarette smoking on the concentration of the adipokines leptin and
      adiponectin and the pro-inflammatory factors CRP, SAA, IL-6 and TNF-a in non
      obese (n=138) and obese (n=175) perimenopausal women of the DRECAN-2005 survey.
      RESULTS: Among non-obese women, adiponectin was significantly lower in smokers
      than in non-smokers (16.88 +/-6.85 vs. 20.63 +/-10.04 microg/ml; P<0.05). Leptin
      tended to lower values, too. Among obese women, none significant differences in
      adiponectin or leptin concentration were observed between smokers and non
      smokers. In obese smokers and obese non-smokers, the adiponectin concentrations
      were significantly lower and the leptin concentrations were significantly higher
      than in non-obese non-smokers. Non-obese smokers showed significantly higher
      leukocyte count (6.50 +/- 1.83 vs. 5.51 +/- 1.31 GPT/l; P<0.001) and serum
      amyloid A concentration (7.81 +/- 1.25 vs. 4.22 +/- 1.43 mg/l; P<0.05) than non
      obese non-smokers. There were only tendencies to higher concentration of CRP, IL
      6, and TNF-alpha. In obese women, moderate cigarette smoking was not associated
      with higher leukocyte count or concentration of SAA. Among non-smokers,
      overweight was associated higher concentration of leptin (22.16 +/- 12.16 vs.
      11.49 +/- 6.37 ng/ml; P<0.001) and with significantly lower concentration of
      adiponectin (16.29 +/- 8.01 vs. 20.77 +/- 9.99 microg/ml; P<0.001). Among
      smokers, overweight was associated with higher leptin concentration only (obese:
      18.62 +/- 13.46 vs. non-obese: 8.84 +/- 4.92 ng/ml; P<0.01). CONCLUSIONS: In non
      obese middle aged women, even moderate cigarette smoking adversely influences the
      serum concentration of adiponectin and SAA. Overweight hides possible effects of
      smoking on cytokines and adipokines.

PMID- 20156720
TI  - Maternal smoking promotes chronic obstructive lung disease in the offspring as
      adults.
AB  - INTRODUCTION: In utero and/or childhood environmental tobacco smoke exposure is
      well known to adversely affect lung function and to depreciate child's health in
      many ways. Fewer studies have assessed the long-term effects on COPD development
      and disease severity in later adulthood. METHODS: COPD patients were interviewed
      using a structured questionnaire regarding their personal as well as the smoking
      habits of their parents. Data were compared with the disease history, e.g. COPD
      exacerbation rate, and their lung function data. RESULTS: Between 2003 and 2004
      COPD patients were recruited a) in a private practice specialized in pulmonary
      medicine (n = 133) and b) in a hospital (n = 158). 75% of their fathers and only
      15.4 of all mothers smoked regularly. COPD patients from smoking mothers had
      lower FEV1 predicted than those raised in household without maternal smoking
      exposure: 39.4 +/- 9.5% vs. 51.9 +/- 6.0% (P = 0.037). Fathers had no effect on
      FEV1 regardless if they are smokers or non-smokers. Rate of severe exacerbations
      requiring hospitalization remained unaffected by parental second hand smoke
      exposure. CONCLUSION: Maternal smoking negatively affects lung function of their
      offspring even in late adulthood when they develop COPD. It even aggravates the
      cumulative effect of active cigarette consumption. Clinical course of the COPD
      remained unaffected.

PMID- 20156721
TI  - Serotoninergic modulation of cortical and respiratory responses to episodic
      hypoxia.
AB  - Biphasic respiratory response to hypoxia in anesthetized animals is accompanied
      by changes in the EEG mostly in the low EEG frequency bands. Serotonin is a
      potent modulator of cortical and respiratory activity through 5-HT(2) receptors.
      Present study investigated whether 5-HT(2) receptors might be involved in the EEG
      and respiratory relationship during normoxic and hypoxic respiration assessed
      from integrated phrenic (Phr) and hypoglossal (HG) nerve activities. EEG signal
      recorded from the frontal cortex was subjected to power spectral analysis in
      delta, theta, alpha, and beta frequency bands. Systemic administration of 5-HT(2)
      agonist DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) enhanced tonic and
      lowered peak phasic respiratory activity, and increased frequency of bursts of
      Phr and HG activity. At the same time, EEG activity became desynchronized and
      arterial blood pressure (ABP) increased. Following DOI pretreatment, 11% hypoxia
      induced an augmented respiratory response in comparison with the response in the
      baseline condition. ABP fell less then in the control hypoxia. EEG pattern
      changed less than in the baseline state. Subsequent administration of ketanserin,
      a 5-HT(2) antagonist increased respiratory activity, elicited a synchronization
      of EEG activity and hypotension. The respiratory response to hypoxia was
      attenuated and cortical response was more potent in comparison with that after
      DOI injection. Arterial blood pressure decreased more then during baseline
      hypoxic response. The results suggest that modulation of cortical synchronization
      and desynchronization through 5-HT(2) receptor active agents may impact to
      hypoxic respiratory response.

PMID- 20156722
TI  - Lung surfactant alterations in pulmonary thromboembolism.
AB  - Beside neonatal respiratory distress syndrome, secondary surfactant deficiency
      may occur in patients with mature lungs. Recent studies revealed quantitative and
      qualitative changes of lung surfactant in pulmonary thromboembolism (PTE)
      concerning the total phospholipids content in BAL fluid, alterations in
      surfactant phospholipids classes and a large-to-small aggregates ratio. Reduced
      expression of surfactant protein A (SP-A) mRNA and SP-A in lung tissue after
      pulmonary embolism was found. Serum levels of SP-A were significantly higher in
      patients with PTE than in other lung diseases, except COPD. Surfactant changes in
      PTE may result from damage of type II cells by hypoxia, leakage of plasma
      proteins into the airspaces and/or by reactive oxygen species. They can
      contribute to lung atelectasis and edema, and a further reduction in oxygen
      saturation as seen in clinical picture of PTE. Surfactant changes are reliable
      marker of lung injury that might become a prognostic indicator in patients with
      pulmonary thromboembolism.

PMID- 20156723
TI  - Neoadjuvant therapy affects tumor growth markers in early stage non-small-cell
      lung cancer.
AB  - INTRODUCTION: While adjuvant therapy of early-stage non-small-cell lung cancer
      (NSCLC) is widely accepted, literature data concerning neoadjuvant treatment
      provide contradictory results with both improved and unaffected survival rates.
      Also, data concerning potential effects of neo-adjuvant therapy on cellular level
      are scarce. OBJECTIVE: The aim of present study was to analyze the effect of
      chemotherapy followed by surgical resection on several key biological markers of
      tumor growth (TGF-beta, VEGF), apoptosis (sAPO-1/Fas/CD95) and invasiveness (TIMP
      1) assessed in the sera of NSCLC early-stage patients (IB-IIIA). - MATERIAL AND
      METHODS: Measurements were performed by ELISA method in blood serum from 24 NSCLC
      patients (I-IIIA) collected prior therapy, one day before surgery and 3 days
      after. RESULTS: TGF-beta serum concentrations were significantly lower after both
      chemotherapy (P<0.05) and surgery (P<0.01) in comparison to the baseline. VEGF
      levels decreased following NEO therapy with subsequent significant up-regulation
      after surgery (P<0.001). Interestingly, post-surgery serum VEGF strongly
      correlated with TGF-beta concentration (r = 0.52, P = 0.014). No significant
      differences were observed for serum sAPO-1/CD95/FAS as well as TIMP-1
      concentrations at any of three evaluated time-points. CONCLUSION: Neoadjuvant
      treatment of early-stage NSCLC affects mostly mechanisms responsible for tumor
      growth and vascularization. Its effect on cancer cells apoptotic activity needs
      further evaluation.

PMID- 20156724
TI  - Cough reflex sensitivity in adolescents with diabetic autonomic neuropathy.
AB  - OBJECTIVE: Diabetic autonomic neuropathy (DAN) is one of the chronic
      complications of diabetes mellitus which can involve one or more organ systems.
      DAN without apparent symptoms is more often in childhood and adolescence. While
      heart rate variability (HRV) and Ewing's battery of cardiovascular tests are
      regarded as a gold standard for the diagnosis of DAN, the examination of cough
      reflex sensitivity (CRS) is another possibility. The aim of this study was to
      compare HRV and CRS in children with diabetes mellitus. MATERIAL AND METHODS:
      Sixty one patients (37 girls, 24 boys) aged 15-19 suffering from diabetes
      mellitus type 1 completed the study. Based on HRV, patients were divided into 2
      groups - with DAN (n=25) and without DAN (n=32), 4 patients were excluded because
      of ambiguous results. CRS was studied in each patient by inhalation of gradually
      increasing concentration of capsaicin. RESULTS: Subjects with DAN required a
      significantly higher concentration of capsaicin needed to evoke 2 coughs (median
      625 micromol/l, IQR 68.4-625.0 micromol/l vs. median 29.3 micromol/l, IQR 9.8
      156.3 micromol/l, P<0.001) and 5 coughs (median 2500.0 micromol/l, IQR 1250.0
      2500.0 micromol/l vs. median 312.5 micromol/l, IQR 117.2-625.0 micromol/l,
      P<0.001) compared with those without DAN. Moreover, a strong negative correlation
      between HRV and CRS was established. CONCLUSION: Diabetes mellitus lowers the
      cough response. Cough reflex sensitivity appears to be another sensitive method
      for the evaluation of DAN in diabetes.

PMID- 20156725
TI  - Endothelium-derived markers and antioxidant status in the blood of obstructive
      sleep apnea males.
AB  - OBJECTIVE: The relationship between obstructive sleep apnea (OSA) and
      cardiovascular disease is intensively discussed. Endothelial leukocyte adhesion
      molecule (E-selectin) is one of factors facilitating leukocyte migration to the
      subendothelial layer which could be considered proatherogenic. The aim of the
      study was to determine E-selectin levels and total plasma antioxidant status
      (TAS) in the blood of different stage OSA patients. METHODS: Non-smoking, OSA
      suspected males, aged 30-63, were selected for the study. An EMBLA
      polysomnographic system was used to establish the severity of apneic episodes.
      The results of apnea/hypopnea index (AHI) allowed dividing patients into the
      following groups: OSA-0 with AHI 0-4.9 (n=14), OSA-1 with AHI 5-15 (n=14), OSA-2
      with AHI 16-30 (n=13), OSA-3 with AHI > or =30 (n=13). Complete blood count
      (CBC), glycemia during oral glucose tolerance test, fasting plasma lipid profile,
      uric acid, and high sensitivity C-reactive protein (hsCRP) were estimated among
      routine parameters. We determined plasma concentrations of E-selectin and total
      antioxidant status. RESULTS: We found progressively decreasing concentrations of
      TAS (P=0.03) and increased concentrations of E-selectin (P=0.0001) from OSA-0 to
      OSA-3 subjects. No correlation between E-selectin and metabolic parameters was
      noted. - CONCLUSION: In the studied OSA groups, E-selectin appeared an
      independent proatherogenic factor.

PMID- 20156726
TI  - Analysis of postural sway in patients with normal pressure hydrocephalus: effects
      of shunt implantation.
AB  - Poor postural balance is one of the major risk factors for falling in normal
      pressure hydrocephalus (NPH). Postural instability in the clinic is commonly
      assessed based upon force platform posturography. In this study we focused on the
      identification of changes in sway characteristics while standing quiet in
      patients with NPH before and after shunt implantation. Postural sway area and
      sway radius were analyzed in a group of 9 patients and 46 controls of both
      genders. Subject's spontaneous sway was recorded while standing quiet on a force
      platform for 30-60 s, with eyes open and then closed. Both analyzed sway
      descriptors identified between-group differences and also an effect of shunt
      implantation in the NPH group. Sway radius and sway area in patients exhibited
      very high values compared with those in the control group. Importantly, the
      effect of eyesight in patients was not observed before shunt implantation and
      reappeared after the surgical treatment. The study documents that static force
      platform posturography may be a reliable measure of postural control improvement
      due to shunt surgery.

PMID- 20156727
TI  - Influence of proinflammatory cytokine gene polymorphism on childhood obesity.
AB  - BACKGROUND: Obesity development is a complex process which can be influenced by
      genetic predisposition modified by environmental factors. Nowadays, the problem
      of overweight and obesity, including related complications, occurs in
      increasingly younger children. Thus, there is a need for new genetic markers of
      increased risk of excessive body mass. OBJECTIVE: The aim of the present study
      was to examine the relation between polymorphisms located in promoter regions of
      IL-1beta, IL-6, and TNF-alpha genes and obesity development in children. Fifty
      obese and 55 normal weighing children were enrolled into the study. Genetic
      examination was performed using PCR-RFLP technique. RESULTS: We found a relation
      between G174C polymorphism in IL-6 gene and G308A in TNF-alpha gene with the
      occurrence of obesity. Allele A in G308A was more frequent in the obese group
      than in the control one (P=0.04). The presence of allele C in promoter region of
      IL-6 gene was more frequent in obese children and connected with a statistically
      significant increase in the sum of 10 skin fold thickness measurements (P=0.03).
      CONCLUSIONS: The polymorphism C3954T in IL-1beta gene showed no such relation.
      The examined polymorphisms of proinflammatory cytokines play a role in the
      regulation of body mass through their influence on metabolism and energetic
      homeostasis.

PMID- 20156728
TI  - Effects of body position on the ventilatory response to hypercapnia.
AB  - Effect of posture on the hypercapnic ventilatory response was studied on the
      anaesthetized rats by using rebreathing techniques in the supine and head-down
      positions. There were no statistically significant alterations in tidal volume,
      frequency, minute ventilation, and P(ET)CO(2)between the head-down and supine
      positions during breathing at rest. However, the esophageal pressure inspiratory
      swings were significantly greater in the head-down compared with supine position.
      Moreover, we found that body position did not affect the hypercapnic ventilatory
      response, but did affect the relationship between inspiratory driving pressure
      and the increase of end tidal PCO(2). Greater inspiratory pressure is required to
      maintain the same level of the ventilatory response to hypercapnia in the
      horizontal position with the head-down. We believe that the discrepancy between
      postural alterations in the hypercapnic ventilatory and pressure responses is
      presumably a result of decreased lung compliance and increased airflow impedance
      of respiratory system in the head-down position.

PMID- 20156729
TI  - Snoring - the role of the laryngologist in diagnosing and treating its causes.
AB  - According to various data, snoring may affect about 2 billion people worldwide,
      with about 8 million adult people in Poland being estimated to snore. Apart from
      being disturbing for other people, it brings about a measurable risk for the
      patient, which results from transient anoxia. As a consequence, it may increase
      the risk of arterial hypertension, myocardial infarction, cerebral stroke and
      impotency, as well as mental disturbances like depression or anxiety states. The
      physician a snoring patient may consult in the first instance is the
      laryngologist. He determines whether upper airway obturation (in contrast to
      central sleep apnea) is dealt with, and takes a decision about treatment method,
      or redirects the patient to another specialist. In this paper, the position of a
      laryngologist in the diagnosis and treatment of snoring is presented. The
      material consisted of patients presenting with this problem at the otolaryngology
      department. The proceedings with patients in the admission office setting were
      described as well as qualification methods for further medical and operative
      treatment. A review of the applied procedures was made, in particular allowing
      for the most recent therapeutic methods.

PMID- 20156730
TI  - Novel devices for individualized controlled inhalation can optimize aerosol
      therapy in efficacy, patient care and power of clinical trials.
AB  - In the treatment of pulmonary diseases the inhalation of aerosols plays a key
      role - it is the preferred route of drug delivery in asthma, chronic obstructive
      pulmonary disease (COPD) and cystic fibrosis. But, in contrast to oral and
      intravenous administration drug delivery to the lungs is controlled by additional
      parameters. Beside its pharmacology the active agent is furthermore determined by
      its aerosol characteristics as particle diameter, particle density,
      hygroscopicity and electrical charge. The patient related factors like age and
      stage of pulmonary disease will be additionally affected by the individual
      breathing pattern and morphometry of the lower airways. A number of these
      parameters with essential impact on the pulmonary drug deposition can be
      influenced by the performance of the inhalation system. Therefore, the
      optimization of nebulisation technology was a major part of aerosol science in
      the last decade. At this time the control of inspiration volume and air flow as
      well as the administration of a defined aerosol bolus was in the main focus. Up
      to date a more efficient and a more targeted pulmonary drug deposition - e.g., in
      the alveoli - will be provided by novel devices which also allow shorter
      treatment times and a better reproducibility of the administered lung doses. By
      such means of precise dosing and drug targeting the efficacy of inhalation
      therapy can be upgraded, e.g., the continuous inhalation of budesonide in asthma.
      From a patients' perspective an optimized inhalation manoeuvre means less side
      effects, e.g., in cystic fibrosis therapy the reduced oropharyngeal tobramycin
      exposure causes fewer bronchial irritations. Respecting to shorter treatment
      times also, this result in an improved quality of life and compliance. For
      clinical trials the scaling down of dose variability in combination with enhanced
      pulmonary deposition reduces the number of patients to be included and the
      requirement of pharmaceutical compounds. This review summarises principles and
      advances of individualised controlled inhalation (ICI) as offered by the AKITA
      inhalation system.

PMID- 20156731
TI  - Effects of flavin7 on allergen induced hyperreactivity of airways.
AB  - Some studies have suggested that the polyphenolic compounds might reduce the
      occurrence of asthma symptoms. The aim of our experiments was to evaluate the
      effects of 21 days of the flavonoid Flavin7 administration on experimentally
      induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed
      tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in
      airway resistance by an in vivo plethysmographic method; histological picture of
      tracheal tissue; and the levels of interleukin 4 (IL-4), and interleukin 5 (IL-5)
      in bronchoalveolar lavage fluid (BALF). Histological investigation of tracheal
      tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF
      were used as indices of airway inflammation. Administration of Flavin7 caused a
      significant decrease of specific airway resistance after histamine nebulization
      and a decline in tracheal smooth muscle contraction amplitude in response to
      bronchoconstricting mediators. Flavin7 minimized the degree of inflammation
      estimated on the basis of eosinophil calculation and IL-4 and IL-5
      concentrations. In conclusion, administration of Flavin7 showed bronchodilating
      and anti-inflammatory effects on allergen-induced airway inflammation.

PMID- 20156732
TI  - Acceptance of NCPAP in a sample of patients admitted for geriatric
      rehabilitation.
AB  - OBJECTIVE: Sleep apnea syndrome (SAS) is common in older people. Nasal continuous
      airway pressure (NCPAP) therapy is the treatment of choice for sleep apnea, but
      is not always accepted by patients. The rate of successful initiation of NCPAP is
      unknown in geriatric patients. METHODS: All patients admitted for geriatric
      rehabilitation were considered for sleep studies. Sleep apnea was assessed using
      an Edentrace (Nellcor, Hayward, CA) multi-channel recording system. SAS was
      defined as an apnea-hypopnea-index (AHI) of more than five events per hour plus
      excessive daytime sleepiness, or an AHI of more than fifteen events per hour
      regardless of reported sleepiness. Disability was assessed using the Barthel
      Index of Activities of Daily Living. RESULTS: Two hundred sixty nine of 322
      consecutive patients (84%) had adequate sleep studies and gave informed consent.
      SAS was found in 169 subjects (68%). There was no gender difference in the
      prevalence of SAS. Six subjects (4%) accepted NCPAP therapy. Individuals who
      accepted NCPAP were younger and less disabled (p<0.03). Multiple logistic
      regression analysis revealed disability as the only significant factor predicting
      NCPAP acceptance. CONCLUSION: NCPAP should not be withheld in the elderly.
      However, initiation of treatment for SAS remains to be a great challenge in those
      patients. Geriatric assessment procedures may help better manage older subjects
      with sleep apnea syndrome.

PMID- 20156733
TI  - Tobacco abuse and physical activity among medical students.
AB  - OBJECTIVE: This lifestyle is mainly determined during childhood and connected
      with poor public prophylactic health policy. The aim of this study was to
      estimate physical activity and level of tobacco abuse, as well as knowledge about
      health behaviours, among medical students. METHODS: Questionnaires were completed
      by Polish (243) and foreign medical students (80). RESULTS: It was stated that
      about 20% of the students smoked cigarettes. Female students from Norway took up
      smoking significantly more often than other participants, whereas there were more
      smokers among those from Poland. There was a significantly larger percentage of
      smoking males from Norway than among male Polish students. The same students
      presented a low level of physical activity. The smallest level of physical
      activity was characteristic of the Polish women. CONCLUSION: This situation
      requires an intensification of activities aimed at supporting pro-health
      lifestyles and the elimination of unfavourable effects, especially among medical
      students.

PMID- 20156734
TI  - Relationship between airway inflammation and remodeling in patients with asthma
      and chronic obstructive pulmonary disease.
AB  - Despite a number of important differences in the pathogenesis, course and
      prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two
      entities also have common features with airway inflammation being one of them.
      Airway remodeling is a characteristic feature of asthma, but data on the
      bronchial wall thickening in COPD patients are still scarce. AIM: To assess the
      relation between the inflammatory cell count in the bronchoalveolar lavage fluid
      (BALF) and thickness of bronchial walls assessed by high resolution computed
      tomography (HRCT) in asthma and COPD patients. MATERIAL AND METHODS: The study
      was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 +/
      10 years) and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 +/- 9
      years). In all subjects lung function tests and HRCT scanning of the chest were
      performed. External (D) and internal (L) diameters of the airways were assessed
      at five selected lung levels. The lumen area (A(L)), wall area (WA), wall
      thickness (WT) and bronchial wall thickness (WT/D ratio) were calculated. Eight
      patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy
      and bronchoalveolar lavage (BAL). Total and differential cell counts were
      assessed in the BAL fluid. RESULTS: Mean FEV(1)% pred was 80 +/- 19%, and 73 +/-
      20% in asthma and COPD patients, respectively (NS). No significant differences in
      the total and differential cell counts in BALF were found in patients with asthma
      and COPD. There were no significant differences in the airway diameter or airway
      wall thickness. The mean inner airway diameter was 1.4 +/- 0.3 and 1.2 +/- 0.3 mm
      and the mean lumen area was 1.8 +/- 0.7 and 1.6 +/- 0.7 mm(2) in asthma and COPD,
      respectively (NS). Negative correlations between the eosinophil count in BALF and
      inner airway diameter (r=-0.7, P<0.05) and lumen area (r=-0.7, P<0.05) were found
      in asthmatics. There was no significant relationship between the BALF cell count
      and airway wall thickness in COPD patients. - CONCLUSIONS: In mild-to-moderate
      asthma and COPD the airway diameter and thickness are similar. In asthmatics, the
      airway diameter might be associated with eosinophil count in BAL fluid.

PMID- 20156735
TI  - Expression of anti-apoptotic protein survivin and tumor suppressor p53 protein in
      patients with pulmonary carcinoma.
AB  - BACKGROUND: Survivin is one of the inhibitors of the apoptosis gene family that
      has been implicated in both inhibition of apoptosis and mitosis regulation. p53
      is one of the tumor suppressor genes; prevents tumor formation through cell cycle
      blocking and eliminates damaged cells via activation of apoptosis. OBJECTIVE: To
      investigate the possible regulation of survivin by p53, we examined the
      expression of both proteins in 67 patients with diagnosed lung cancer using
      immunohistochemical visualization. RESULTS: Survivin was predominantly expressed
      in both nucleus and cytoplasm, whereas p53 was expressed in the nucleus. There
      was a negative correlation between survivin and p53 expression. A decreased
      intensity of expression and fewer cells positive for survivin in small cell lung
      cancer in comparison with other lung cancer types were detected. There was no
      significant difference in the intensity of expression and the number of cells
      positive for p53 between small cell and non-small cell lung cancer types.
      CONCLUSION: The present study suggests that survivin expression, as opposed to
      that of p53, is decreased in small cell lung cancer, which may differentiate this
      cancer from other lung cancer types other types.

PMID- 20156736
TI  - Cardiac autonomic control in adolescents with primary hypertension.
AB  - BACKGROUND: Impairment in cardiovascular autonomic regulation participates in the
      onset and maintenance of primary hypertension. OBJECTIVE: The aim of the present
      study was to evaluate cardiac autonomic control using long-term heart rate
      variability (HRV) analysis in adolescents with primary hypertension. SUBJECTS AND
      METHODS: Twenty two adolescent patients with primary hypertension (5 girls/17
      boys) aged 14-19 years and 22 healthy subjects matched for age and gender were
      enrolled. Two periods from 24-hour ECG recording were evaluated by HRV analysis:
      awake state and sleep. HRV analysis included spectral power in low frequency band
      (LF), in high frequency band (HF), and LF/HF ratio. - RESULTS: In awake state,
      adolescents with primary hypertension had lower HF and higher LF and LF/HF ratio.
      During sleep, HF was lower and LF/HF ratio was higher in patients with primary
      hypertension. CONCLUSIONS: A combination of sympathetic predominance and reduced
      vagal activity might represent a potential link between psychosocial factors and
      primary hypertension, associated with increased cardiovascular morbidity.

PMID- 20156737
TI  - Nuclear HSP90 and HSP70 in COPD patients treated with formoterol or formoterol
      and corticosteroids.
AB  - OBJECTIVE: Heat shock proteins assist cellular protein folding and are required
      for the normal activity of steroid receptors. In this study we assessed nuclear
      HSP90 and HSP70 proteins and mRNA levels in cells isolated from induced sputum of
      chronic obstructive pulmonary disease patients treated for 4 weeks with
      formoterol (F) or formoterol+budesonide (F/ICS). METHODS: Nuclear heat shock
      protein levels were assessed by Western blot and specific mRNAs were quantified
      in cell lysates using qRT-PCR. RESULTS: Both HSP90 and HSP70 protein levels were
      higher in the F/ICS-treated patients in comparison with the F-treated group (by
      31%, P<0.05 and 28%, P<0.05, respectively), while specific mRNAs were lowered.
      HSP86/HSP89 and D6S182/HSP90-BETA were repressed by about 40% (P<0.05) while
      HSP70-1/HSP70-1A, HSP70-1B/HSP70-2, and HSP70-HSC54/HSC70 were repressed by 47%
      (P<0.01), 57% (P<0.01) and 65% (P<0.01), respectively. CONCLUSIONS: It is
      possible that increased nuclear heat shock proteins may play a role in the
      attenuation of the response to glucocorticoids in COPD patients.

PMID- 20156738
TI  - Increased FKBP51 in induced sputum cells of chronic obstructive pulmonary disease
      patients after therapy.
AB  - OBJECTIVE: Immunophilin FKBP51 assists polypeptide folding, participates in
      glucocorticoid actions and may play a role in glucocorticoid resistance. FKBP51
      is altered in patients with asthma, but its role in chronic obstructive pulmonary
      disease (COPD) characterized by dysregulation of several pro/antiinflammatory
      genes is less clear. METHODS: We assessed changes in nuclear/cytosolic FKBP51
      protein using SDS-PAGE/WB and FKBP51 mRNA by qRT-PCR in cells isolated from
      induced sputum of stable COPD patients treated with formoterol/budesonide or
      formoterol/budesonide/theo?phylline for 4 wk. RESULTS: Expression of FKBP51 was
      higher in formoterol/ budesonide/theophylline-treated patients, compared with
      formoterol/budesonide group in both cytosolic and nuclear fractions by about 57%
      and 31%, respectively (P<0.001, P<0.01). FKBP51 mRNA was only slightly, but not
      significantly, higher in patients on formoterol/ budesonide/theophylline.
      CONCLUSIONS: Increased FKBP51 in COPD patients treated with formoterol/
      budesonide/theophylline may be important in altering signaling from
      corticosteroid receptors.

PMID- 20156739
TI  - Idiopathic pulmonary hemosiderosis in a 9-year-old girl.
AB  - Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening condition
      characterized by hemoptysis, dyspnoea, alveolar infiltrates on chest radiograph
      and various degrees of anemia. It may occur either as a primary disease of the
      lungs or a secondary condition due to cardiac, systemic vascular, collagen or
      renal diseases. Idiopathic pulmonary hemosiderosis (IPH) is a separate form of
      DAH of unknown origin, associated in some cases with celiac disease. The
      estimated incidence of IPH in children is 0.24-1.23 cases per million, with a
      mortality rate as high as 50%. Only about 500 cases of this disease have been
      described in medical literature. We present a case of a 9-year-old girl diagnosed
      with IPH, which was confirmed by the presence of many hemosiderin-laden
      macrophages in bronchoalveolar lavage obtained by bronchofiberoscopy. Therapy
      with glucocorticoids was initiated with a partial and transient response.
      Azathioprine and a gluten-free diet were subsequently introduced. However, the
      girl still suffers from recurrent episodes of hemoptysis, dyspnea and anemia.

PMID- 20156740
TI  - Effects of long-term oxygen treatment on alpha-ketoglutarate dehydrogenase
      activity and oxidative modifications in mitochondria of the guinea pig heart.
AB  - OBJECTIVE: Oxygen therapy is used for the treatment of various diseases, but
      prolonged exposure to high concentrations of O(2) is also associated with
      formation of free radicals and oxidative damage. METHODS: In the present study we
      compared alpha-ketoglutarate dehydrogenase (KGDH) activity and mitochondrial
      oxidative damage in the hearts of guinea pigs after long-term (17 and 60 h)
      oxygenation with 100% normobaric O(2) and with partially negatively (O(2 neg)) or
      positively (O(2 posit)) ionized oxygen. RESULTS: Inhalation of O(2) led to
      significant loss in KGDH activity and thiol group content and accumulation of
      bityrosines. Inhalation of O(2 neg) was accompanied by more pronounced KGDH
      inhibition, possibly due to additional formation of protein-lipid conjugates. In
      contrast, O(2 posit) prevented loss in KGDH activity and diminished mitochondrial
      oxidative damage. CONCLUSIONS: These findings suggest that oxygen treatment is
      associated with impairment of heart energy metabolism and support the view that
      inhalation of O(2 posit) optimizes the beneficial effects of oxygen therapy.

PMID- 20156741
TI  - Differential ion mobility spectroscopy: non-invasive real-time diagnostics and
      therapy control in metabolic diseases.
AB  - BACKGROUND: Over the last few years, differential ion mobility spectroscopy (DMS)
      has become an important tool in medical research. There are attempts to find
      markers for specific diseases in exhaled air, using this technology as a non
      invasive early diagnosis. OBJECTIVE: In the present research, exhaled air from 78
      patients with known diagnosis and 39 control persons were tested with a DMS
      system from Sionex. RESULTS: Bronchial asthma showed a pattern of 6
      characteristic points in a discriminant analysis. Patients with diagnosed
      hypertension showed a characteristic pattern with 4 points, hypothyroidism 2
      points; increased LDL cholesterol 3 points, and type II diabetics treated with
      insulin 4 spots. No significant differences with respect to the control group
      were found in chronic obstructive pulmonary disease patients. The DMS pattern in
      the tested asthmatics showed a partial change depending on different medications
      used. CONCLUSION: Differential ion mobility spectroscopy offers promise as a
      helpful diagnostic tool.

PMID- 20156742
TI  - Reflex influence of carotid baroreceptor inactivation on respiratory resistance
      in humans.
AB  - Our previous study demonstrated that selective carotid baroreceptors activation
      decreases airway resistance. The aim of the present study was to evaluate the
      effect of carotid baroreceptor inactivation on the reflex change of respiratory
      resistance. Twenty healthy men aged between 20 and 25 were included in the study.
      Selective inactivation of carotid baroreceptors was induced by generating a
      positive pressure of 40 mmHg for 5 s in two capsules placed bilaterally on the
      neck over the bifurcation of the carotid arteries. The oscillatory method
      (Siregnost FD5, Siemens) was used to measure continuously respiratory resistance.
      Inactivation of carotid baroreceptors produced a short increase in respiratory
      resistance by 0.39 +/- 0.01(SE) mbar/l/s, i.e., 21.7% above the resting level. We
      conclude that in humans, carotid baroreceptors might have a background
      contribution to bronchodilator tone. This observation seems to be important for
      clinical situations of impairment of baroreflex function.

PMID- 20156743
TI  - Diagnostic utility of pleural fluid and serum markers in differentiation between
      malignant and non-malignant pleural effusions.
AB  - STUDY OBJECTIVE: To evaluate the diagnostic value of four different tumor
      markers: cancer antigen 125 (CA-125), carcinoembryonic antigen (CEA), cytokeratin
      19 fragment (CYFRA 21-1) and neuron specific enolase (NSE) in patients with
      malignant and non-malignant pleural effusion. MATERIAL AND METHODS: One hundred
      and two patients with pleural effusion treated in the University Hospital in
      Warsaw between 2001 and 2003 were studied. They underwent an extensive,
      diagnostic work-up in order to determine the pleural effusion etiology. Patients
      with known pleural fluid etiology were labeled as the study group and submitted
      for further analysis. Pleural fluid and serum samples for CA-125, CEA, CYFRA 21-1
      and NSE measurements were collected during the first thoracentesis, centrifuged,
      and frozen until further use. Pleural fluid and serum concentration of tumor
      markers were assessed by electrochemiluminescence methods using commercial kits.
      RESULTS: 74 patients (32 M, 42 F; mean age 65 +/-14 years) composed the final
      study group. Exudative pleural effusion was found in 62 patients; of these 36
      were malignant (48.6% of all effusions), 20 parapneumonic (or pleural empyema),
      and 6 tuberculous. In 12 patients, pleural transudate was diagnosed. The highest
      diagnostic sensitivity for malignant pleural effusion was found for NSE (94.4%
      and 80.6% in the pleural fluid and serum, respectively). However, the specificity
      of NSE measurement was relatively low (36.1% and 47.4% in pleural fluid and
      serum, respectively). The most specific markers of malignant pleural fluid
      etiology were pleural fluid CYFRA 21-1 and CEA levels (92.1% and 92.1%,
      respectively). CA-125 was found to be the most specific serum marker of pleural
      malignancies (78.9%). The AUC for combined pleural markers was 0.89, combined
      serum markers 0.82, combined ratio pleural/serum markers 0.88. CONCLUSIONS: There
      are significant differences between the diagnostic value of various pleural fluid
      and serum markers. Overall, pleural fluid markers are superior to serum markers
      in determining the pleural fluid etiology. A combination of two or more tumor
      markers may help improve their diagnostic accuracy. Pleural fluid and serum
      measurements of different tumor markers play a limited role in the
      differentiation between malignant and non-malignant pleural effusions.

PMID- 20156744
TI  - Hydrogen peroxide release and acid-base status in exhaled breath condensate at
      rest and after maximal exercise in young, healthy subjects.
AB  - OBJECTIVE: Exhaled breath condensate (EBC) contains among a large number of
      mediators hydrogen peroxide (H2O2) as a marker of airway inflammation and
      oxidative stress. Similarly EBC pH also changes in respiratory diseases. It was
      the aim of our investigation to prove if hydrogen peroxide release and changes in
      pH of EBC changes with exercise. METHODS: EBC was collected from 100 litres
      exhaled air along with samples of arterialized blood of 16 healthy subjects (9
      males, 7 females, age 23 +/- 1 years). EBC hydrogen peroxide was analyzed with
      EcoCheck amperometer (FILT, Berlin). The rate of H(2)O(2) release was calculated
      from the concentration and collection time. pH and PCO(2) in blood and in EBC
      were measured with the Radiometer blood gas analyzer, EBC was equilibrated with a
      gas mixture (5% CO(2) in O(2)). The bicarbonate concentration was calculated
      according to the law of mass action for CO(2) and HCO(3)(-) (pK = 6.1). RESULTS:
      H(2)O(2) concentration in EBC was 190 +/- 109 nmol/l, and H (2)O(2) release at
      rest was 31.0 +/- 18.3 pmol/min. At maximal exercise, the H(2)O(2) concentration
      in EBC increased to 250 +/- 120 nmol/l, and H(2)O(2) release significantly
      increased at maximal exercise to 84.4 +/- 39.9 pmol/min (P<0.01). At rest pH of
      the CO(2) equilibrated EBC was at 6.08 +/- 0.23 and the [HCO(3)(-)] was 1.03 +/-
      0.40 mmol/l. At maximum exercise, pH 6.18 +/- 0.17 and [HCO(3)(-)] 1.23 +/- 0.30
      mmol/l remained almost unaltered. CONCLUSIONS: The rate of H(2)O(2) release in
      EBC increased during exhausting exercise (external load: 300 Watt) by a factor of
      2, whereas the pH and the bicarbonate concentration of the EBC, equilibrated with
      5% CO(2) at 37 degrees C were not significantly altered. It has to be proven by
      further experiments whether there is a linear relationship between the rates of
      H(2)O(2) release in EBC in graded submaximal exercise.

PMID- 20156745
TI  - Time for new reference values for ventilatory lung function.
AB  - OBJECTIVE: The anthropometrical data of our aging population has significantly
      changed within the last five decades. Therefore the question arises whether or
      not the commonly used reference values of the European Community (ECCS) for lung
      function, may still be accepted today. Measured values for elderly are classified
      by extrapolation beyond the range of reference equations. MATERIAL AND METHODS:
      Lung function was examined by pneumotachography for recording static lung volumes
      and flow-volume-curves in 257 asymptomatic non smoking males, aged 20-90 years.
      Results were compared to the reference values of ECCS, SAPALDIA, LuftiBus, and
      NHANES. RESULTS: For analysis age and height dependence of investigated
      respiratory parameters (VC, FVC, FEV(1), FEV(1) %FVC, PEF, MEF(75,50,25)) can for
      simplicity be described by linear functions (y = a . height(H)-b . age (A)+c).
      The forced expiratory volume in one second, FEV(1), was calculated by FEV(1) =
      0.0432 . H-0.0347 . A -2.114; where H - height, A - age; r = 0.78. Mean FEV(1)
      for younger subjects was found to be 106.1 +/- 11.2% of the ECCS reference values
      and 97.8 +/- 11.7% in older subjects. For all parameters investigated linear
      regressions on age were steeper than described by the ECCS reference values. The
      regression of lung function to height largely follows the ECCS prescriptions.
      SUMMARY: Bochum lung function values of healthy subjects showed a steeper age
      descent compared to the reference values of the ECCS. The alternatively discussed
      reference values of the SAPALDIA-, NHANES- or LuftiBus-Study are higher, but do
      not cover all necessary parameters and/or the age range. A multi centre study for
      contemporary reference values is recommended.

PMID- 20156746
TI  - Quality of life and activity of children suffering from bronchial asthma.
AB  - OBJECTIVE: The aim of this article was to analyze the quality of life of children
      suffering from bronchial asthma and to analyze their everyday activity. METHODS:
      The research was conducted in 137 children. The following questionnaires were
      used in the study: Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and a
      questionnaire designed by the authors specifically for the purpose of the study.
      RESULTS: The findings of the study show that illness duration (r = -0.2; P =
      0.22) and gender (P = 0.37) do not influence the quality of life. It appears that
      among children ill with asthma a higher level of quality of life is typical for
      the children who live in the country side in comparison with those from cities (P
      <0.05). The comparison was also made in terms of everyday activity of children
      ill with asthma and non-asthmatic children. The children ill with asthma
      displayed less social contacts with peers/friends (P <0.05) and they performed
      less physical activities (P <0.05). CONCLUSIONS: The study points to the possible
      beneficial effects of activating children's social interactions, creating
      conditions for appropriate development of their social competences, and of stress
      reduction connected with social interactions. Asthmatic children should also be
      encouraged to intensify appropriate physical activity.

PMID- 20156747
TI  - Sympathetic hyperactivity influences chemosensor function in patients with end
      stage renal disease.
AB  - BACKGROUND: Autonomic neuropathy is common in patients suffering from end-stage
      renal disease (ESRD). This may in part explain the high cardiovascular mortality
      in these patients. Chemosensory function is involved in autonomic cardiovascular
      control and is mechanistically linked to the sympathetic tone. OBJECTIVE: The aim
      of the present study was to assess whether sympathetic hyperactivity contributes
      to an altered chemosensory function in ESRD. MATERIAL AND METHODS: In a
      randomized, double-masked, placebo controlled crossover design we studied the
      impact of chemosensory deactivation on heart rate, blood pressure and oxygen
      saturation in 10 ESRD patients and 10 age and gender matched controls. The
      difference in the R-R intervals divided by the difference in the oxygen pressures
      before and after deactivation of the chemoreceptors by 5-min inhalation of 7 L
      oxygen was calculated as the hyperoxic chemoreflex sensitivity (CHRS). Placebo
      consisted of breathing room air. Baseline sympathetic activity was characterized
      by plasma catecholamine levels and 24-h time-domain heart rate variability (HRV)
      parameters. RESULTS: Plasma norepinephrine levels were increased (1.6 +/- 0.4 vs.
      5.8 +/- 0.6; P<0.05) while the SDNN (standard deviation of all normal R-R
      intervals: 126.4 +/- 19 vs. 100.2 +/- 12 ms), the RMSSD (square root of the mean
      of the squared differences between adjacent normal R-R intervals: 27.1 +/- 8 vs.
      15.7 +/- 2 ms), and the 24-h triangular index (33.6 +/- 4 vs. 25.7 +/- 3; each
      P<0.05) were decreased in ESRD patients as compared to controls. CHRS was
      impaired in ESRD patients (2.9 +/- 0.9 ms/mmHg, P<0.05) as compared to controls
      (7.9 +/- 1.4 ms/mmHg). On multiple regression analysis 24 h-Triangular index,
      RMSSD, and plasma norepinephrine levels were independent predictors of an
      impaired hyperoxic CHRS. CONCLUSION: Sympathetic hyperactivity influences
      chemosensory function in ESRD resulting in an impaired hyperoxic CHRS.

PMID- 20156748
TI  - Onconeuronal and antineuronal antibodies in patients with neoplastic and non
      neoplastic pulmonary pathologies and suspected for paraneoplastic neurological
      syndrome.
AB  - OBJECTIVE: Onconeuronal antibodies are important diagnostic tool in patients with
      suspicion of paraneoplastic neurological syndromes (PNS). However, their role in
      PNS pathophysiology and specificity for particular neurological manifestation
      remains unclear. The aim of this study was to evaluate onconeuronal and
      antineuronal antibodies in patients with pulmonary pathologies and suspected for
      PNS. MATERIAL AND METHODS: Twenty one patients with pulmonary pathologies were
      selected from the database of 525 consecutive patients with suspicion of PNS.
      Patients' sera were screened for the presence of onconeuronal and antineuronal
      antibodies by means of indirect immunofluorescence; the presence was confirmed by
      Western blotting. Clinical data were obtained from medical records, hospital data
      base, and questionnaire-based direct telephone contact with patients. RESULTS:
      Among 21 patients, aged 54 +/-11, with pulmonary pathologies, the most frequent
      neurological manifestations were neuropathies. Typical PNS included
      paraneoplastic cerebellar degeneration (PCD) and limbic encephalitis (LE). We
      found cases with multiple onconeuronal antibodies (anti-Ri and anti-Yo) and
      coexisting PNS (PCD/LE). Well-defined onconeuronal antibodies were identified in
      23.8% of patients. Among antineuronal antibodies, the most frequent were anti-MAG
      (23.8%). ROC curves analysis revealed high sensitivity of onconeuronal and
      antineuronal antibodies for typical PNS and lower for pulmonary malignancies.
      CONCLUSIONS: Tests for antibodies are highly sensitive for the diagnosis of
      typical paraneoplastic neurological syndromes. Anti-myelin and anti-MAG
      antibodies are associated with non-neoplastic pulmonary diseases. Patients with
      well-defined onconeuronal antibodies require careful screening and follow-up,
      because the PNS diagnosis indicates a high probability of an underlying
      malignancy.

PMID- 20156749
TI  - Dermatomyositis masquerading as pulmonary embolism.
AB  - A 61-year-old Caucasian was admitted to Department of Chest Diseases and
      Tuberculosis, Medical University of Bialystok, Poland for progressive muscle
      weakness and weight loss. Eighteen months prior to admission, the patient had
      been diagnosed with pulmonary embolism. At that point he was started on
      Enoxaparin QD. Past medical history was unremarkable. In the interim, the patient
      developed fever, myalgia and progressive dyspnea. Physical examination on
      admission revealed a rash on his upper torso and back, and the extensor surfaces
      of all four extremities. Laboratory values included CPK 8229, MB fraction 219,
      LDH 981. Chest X-ray and CT scan revealed bilateral patchy consolidations and
      ground-glass opacities. EMG was consistent with myositis. The patient was started
      on solumedrol 40 mg i.v., b.i.d., and then switched to prednisone 40 mg b.i.d.
      His symptoms and muscle strength improved remarkably. The patient was discharged
      with prednisone with an outpatient follow up.

PMID- 20156750
TI  - Increased levels of Treg cells in bronchoalveolar lavage fluid and induced sputum
      of patients with active pulmonary sarcoidosis.
AB  - OBJECTIVE: It has recently been described that circulatory and BAL regulatory T
      cells (Tregs), defined as CD4+CD25highCD127low are increased in patients with
      active sarcoidosis compared with other interstitial lung diseases. MATERIAL AND
      METHODS: We studied prospectively 17 patients (10 women, 7 men) of median age 39
      years (range 27-65) with active granulomatous lung diseases (GLD) (10 patients
      with sarcoidosis (BBS), and 7 with hypersensitivity pneumonitis (HP), and 9
      healthy controls. Bronchoalveolar lavage fluid (BAL) and induced sputum Treg
      counts, CD4+, CD8+, CD25+ cells were quantified by flow cytometry. Disease
      activity was measured by ACE serum level. Pulmonary function tests were performed
      using an Elite DL Medgraphics body box. RESULTS: We found Treg cells count
      significantly elevated in induced sputum from active GLD (38.3% vs. 7.1% and 5.3%
      in BBS, HP, and control, respectively). A significantly higher percentage of Treg
      cells characterized BAL cells from HP patients (2.27%; 9.5%; 2.1%, in BBS, HP and
      control, respectively). There was a strong correlation with ACE serum level and
      Treg cell count in BAL fluid of BBS patients, with no such correlation within HP
      patient group, nor Treg cell count and pulmonary function tests. CONCLUSIONS: Our
      data suggest a potential role of CD4+CD25highCD127low induced sputum and BAL
      lymphocytes from patients with active granulomatous lung diseases and
      hypersensitivity pneumonitis. An increased number of Treg cells in active GLD may
      be involved in immune regulation in active granulomatous lung diseases. The
      results indicate that analysis of these cells could be useful as markers of
      disease activity in granulomatous lung diseases.

PMID- 20156751
TI  - Assessment of airway hyperreactivity: comparison of forced spirometry and body
      plethysmography for methacholine challenge tests.
AB  - INTRODUCTION: Bronchial challenge tests by inhalation of aerosolized methacholine
      (MCH) are commonly used in the clinical diagnosis of airway hyperresponsiveness
      (AHR). While the detection of airway narrowing relies on the patient's
      cooperation performing forced spirometry, body plethysmographic measurements of
      airway resistance are less depending on the patient's cooperation and do not
      alter the respiratory tract by maximal maneuvers. Hence we compared both methods
      concerning their clinical value and correlation during MCH challenges in patients
      with asthma. MATERIAL AND METHODS: Cumulative MCH challenges test, consisting of
      up to 5 steps, evaluated with body plethysmography on each step were performed in
      155 patients with bronchial asthma. Airway responses were recorded at each step
      of MCH application (MasterScreen Body, Cardinal Health, Hochberg). At the
      baseline test and after crossing the provocation dose (PD) threshold in body
      plethysmography (PD+100 sReff), forced expirations were performed and FEV(1),
      FVC, and FEV(1) %FVC were measured. Using regression analysis of the airway
      parameters and taking the MCH dose as the covariate, we could extrapolate to
      missing spirometric values and interpolate the estimated MCH dose when crossing
      the PD threshold (PD-20 FEV(1)) between two consecutive measurements. The
      administered PD+100 MCH doses for specific airway resistance, sRtot, and sReff
      were compared with resistance parameters Rtot and Reff, and to PD-20 of FEV(1)
      and FEV(1) %FVC. RESULTS: Regarding sReff we found a mild, moderate, or severe
      AHR in 114 patients (75%), but only 50 (32%) according to FEV1. A statistical
      analysis showed strongly linear correlated parameters of airway resistance, but
      no significant correlation between the results of body plethysmography and forced
      spirometry. CONCLUSIONS: Using MCH challenges, we found specific airway
      resistance to be the most sensitive parameter to detect AHR. Raw is largely
      independent of height and gender facilitating the interpretation of measurements
      carried out longitudinally.

PMID- 20156752
TI  - Angiotensin-converting enzyme I/D polymorphism in chronic obstructive pulmonary
      disease.
AB  - STUDY OBJECTIVE: The etiology of chronic obstructive lung disease (COPD) is
      unclear. It is supposed to be the product of an exogenous antigenic stimulus,
      such as tobacco smoke, and an endogenous genetic susceptibility. The angiotensin
      converting enzyme (ACE) gene contains a polymorphism based on the presence
      (insertion [I]) or absence (deletion [D]) of a 287-bp nonsense domain, resulting
      in three different genotypes (II, ID and DD). The aim of the study was to find
      out whether the ACE gene polymorphism can determine the course of COPD. PATIENTS
      AND DESIGN: We genotyped 152 Caucasian patients with COPD and 158 healthy
      controls for the ACE (I/D) polymorphism. We divided the COPD group into one group
      of 64 patients with a stable course of disease, defined as less than three
      hospitalizations over the last three years due to COPD, and another group of 88
      patients with an instable course with more than three hospitalizations. RESULTS:
      The I-allele was significantly associated with an increased risk for COPD in a
      dominant model (OR 1.67 (95% CI 1.00 to 2.78), p=0.048), but not in a recessive
      or co-dominant model. Moreover, the I-allele of ACE (I/D) was significantly
      increased in patients with a stable course of COPD (p=0.012) compared with
      controls. In a dominant model (II/ID v DD) we found an even stronger association
      between the I-allele and a stable course of COPD (OR 3.24 (95% CI 1.44 to 7.31),
      p=0.003). CONCLUSION: These data suggest that the presence of an ACE I-allele
      determines a stable course of COPD.

PMID- 20156753
TI  - ADAM33 gene polymorphisms in chronic obstructive pulmonary disease.
AB  - STUDY OBJECTIVE: The pathogenesis of chronic obstructive pulmonary disease (COPD)
      is characterized by an interaction of environmental influences, particularly
      cigarette smoking, and genetic determinants. Given the global increase in COPD,
      research on the genomic variants that affect susceptibility to this complex
      disorder is reviving. In the present study, we investigated whether single
      nucleotide polymorphisms in "a disintegrin and metalloprotease" 33 (ADAM33) are
      associated with the development and course of COPD. PATIENTS AND DESIGN: We
      genotyped 150 German COPD patients and 152 healthy controls for the presence of
      the F+1 and S_2 SNPs in ADAM 33 that lead to the base pair exchange G to A and C
      to G, respectively. To assess whether these genetic variants are influential in
      the course of COPD, we subdivided the cohort into two subgroups comprising 60
      patients with a stable and 90 patients with an unstable course of disease.
      RESULTS: In ADAM33, the frequency of the F+1 A allele was 35.0% among stable and
      43.9% among unstable COPD subjects, which was not significantly different from
      the 35.5% found in the controls (P = 0.92 and P = 0.07, respectively). The
      frequency of the S_2 mutant allele in subjects with a stable COPD was 23.3% (P =
      0.32), in subjects with an unstable course 30.6% (P = 0.47). CONCLUSION: The
      study shows that there is no significant difference in the distribution of the
      tested SNPs between subjects with and without COPD. Furthermore, these
      polymorphisms appear to have no consequences for the stability of the disease
      course.

PMID- 20156754
TI  - Influence of allergic disorders on physical development.
AB  - The aim of the paper was to asses the relationship between socioeconomic status,
      the prevalence of allergy and physical development. The data were obtained from
      478 female students and 195 male students aged 19-24. The prevalence of allergy
      in the group surveyed was 14.6% (14.6% in women and 14.4% in men). Allergic
      diseases were more frequent in students of high socioeconomic status. The results
      of the analysis of variance did not show any significant differences in
      anthropometric characteristics between students with and without allergies.
      However, women and men with allergies diagnosed are on average shorter than
      people without allergies. The dependency is also visible after adjusting for
      socioeconomic status. As for the equal status groups, the people with allergies
      are always shorter than those without allergies. Summarizing, the results of the
      tests presented indicate that allergic diseases may affect the growing process.
      However, upon providing appropriate conditions, the growth of children with
      allergy is not different from the control population.

PMID- 20156755
TI  - T lymphocyte apoptosis in asthma.
AB  - The paper describes the possible role of apoptosis of T lymphocytes in asthma
      pathogenesis. The authors focused on resistance against Fas-mediated programed
      cell death and the role of Bcl-2 protein in impaired programed cell death
      process. The reports from the literature regarding the imbalance of Th1 and Th2,
      caused by impaired apoptosis of T cells, in asthma pathogenesis are reviewed.

PMID- 20156756
TI  - Association between metabolic disturbances and G-174C polymorphism of interleukin
      6 gene in obese children.
AB  - OBJECTIVE: The aim of the study was to investigate whether the G-174C
      polymorphism of the IL-6 gene is related to obesity and the incidence of the
      metabolic syndrome (MetS) according to IDF definition in children. MATERIALS AND
      METHODS: The examined group included 124 obese children with BMI > or = 2 SDS,
      and the control group consisted of 56 non-obese children with BMI <1.0 SDS.
      Polymorphism identification was performed in total genomic DNA using PCR-RFLP
      method. RESULTS: In the obese children, carriers of C allele in homozygotic and
      heterozygotic genotypes were more frequent than in the control group. The
      carriers of C alleles presented with lower thickness of subcutaneous tissue and
      higher concentrations of HDL-C than the wild type. The incidence of MetS was 33%
      of the group of obese children. Analysis of the presence of MetS factors showed
      that there is more frequent MetS in the group with the wild homozygous genotype
      type. CONCLUSION: Polymorphism 174G>C in the IL-6 gene does not seem to be
      associated with obesity and with the incidence of MetS in children.

PMID- 20156757
TI  - No association of LEPR Gln223Arg polymorphism with leptin, obesity or metabolic
      disturbances in children.
AB  - OBJECTIVE: The aim of the study was to investigate whether the Gln223Arg in the
      leptin receptor may influence body weight, leptin concentration, and metabolic
      parameters in children. MATERIALS AND METHODS: The examined group included 101
      obese children (58 girls and 43 boys) with BMI 31.41 +/-5.03 kg/m(2) (BMI > or =
      2 SDS) and the control group consisted of 41 children with BMI 20.0 +/-0.80 kg/m2
      (BMI <1.0 SDS). Polymorphism identification was performed in total genomic DNA
      using PCR-RFLP method. RESULTS: The distribution of genotypes LEPR was the
      following: in the obese group: AA - 20.8%, AG- 55.4%, GG-23.8 %; in the control
      group AA-31.7%, AG- 53.65%, GG-14.65%. Comparative analyses between AA homozygous
      children and carriers of G alleles did not confirm any relation between the
      analyzed polymorphism and BMI, leptin concentrations, and metabolic disturbances
      in children with obesity. CONCLUSION: In children with obesity we did not observe
      association of the LEPR Gln223Arg gene polymorphism with obesity, leptin, insulin
      resistance, and metabolic abnormalities.

PMID- 20156758
TI  - Anti-inflammatory effects of Myrtol standardized and other essential oils on
      alveolar macrophages from patients with chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Myrtol standardized is established in the treatment of acute and
      chronic bronchitis and sinusitis. It increases mucociliar clearance and has muco
      secretolytic effects. Additional anti-inflammatory and antioxidative properties
      have been confirmed for Myrtol standardized, eucalyptus oil, and orange oil in
      several in vitro studies. OBJECTIVE: The aim of this study was to prove the
      ability of essential oils to reduce cytokines release and reactive oxygen species
      (ROS) production derived from ex vivo cultured alveolar macrophages. MATERIAL AND
      METHODS: Alveolar macrophages from patients with chronic obstructive pulmonary
      disease (COPD, n=26, GOLD III-IV) were pre-cultured with essential oils (10(3)
      10(-8)%) for 1 h and then stimulated with LPS (1 microg/ml). After 4 h and 20 h
      respectively a) cellular reactive oxygen species (ROS) using 2',7'
      dichlorofluorescein (DCF), and b) TNF-alpha, IL-8, and GM-CSF secretion were
      quantified. RESULTS: In comparison with negative controls, pre-cultured Myrtol,
      eucalyptus oil and orange oil (10-4%) reduced in the LPS-activated alveolar
      macrophages ROS release significantly after 1+20 h as follows: Myrtol -17.7%
      (P=0.05), eucalyptus oil -21.8% (P<0.01) and orange oil -23.6% (P<0.01). Anti
      oxidative efficacy was comparable to NAC (1 mmol/l). Essential oils also induced
      a TNF-alpha reduction: Myrtol (-37.3%, P<0.001), eucalyptus oil (-26.8%, P<0.01)
      and orange oil (-26.6%, P<0.01). TNF-a reduction at 1+4 h and 1+20 h did not vary
      (Myrtol: -31.9% and -37.3% respectively, P= 0.372) indicating that this effect
      occurs early and cannot be further stimulated. Myrtol reduced the release of GM
      CSF by -35.7% and that of IL-8 only inconsiderably. CONCLUSIONS: All essential
      oils tested have effective antioxidative properties in ex vivo cultured and LPS
      stimulated alveolar macrophages. Additionally, Myrtol inhibited TNF-a and GM-CSF
      release best indicating additional potent anti-inflammatory activity.

PMID- 20156759
TI  - Glucocorticoid receptor gene polymorphisms and potential association to chronic
      obstructive pulmonary disease susceptibility and severity.
AB  - OBJECTIVE: As chronic obstructive pulmonary disease (COPD) is known for poor
      glucocorticoid (GC) response, we hypothesized that polymorphic variants of the
      glucocorticoid receptor (GR) gene might predispose for COPD and/or disease
      severity. MATERIAL AND METHODS: Three out of about 50 of the most abundant
      receptor GR gene polymorphisms were investigated in a case-control study which
      included 207 patients with chronic bronchitis or COPD (mean FEV1 50.5% predicted,
      GOLD I-IV) and 106 age matched healthy subjects (mean FEV1 101.8% predicted).
      These were genotyped: a) for the N363S (Exon 2; 1220 A > G (I)); b) the BCLI
      restriction fragment length polymorphism (Intron 2; 647 C >G (II)); and c) the
      ER2223EK (Exon 2; 198, 200 G >A (III)), using RT-PCR and PCR-RFLP method on
      genomic DNA isolated from EDTA blood. RESULTS: Genotype distribution between COPD
      and healthy subjects were alike in all of these three polymorphisms. N363S was
      found in 0.94% of the healthy and 0% of the COPD subjects. BCLI was detected in
      11.3% of the controls and 15.5% of the COPD patients whereas heterozygote
      frequency was less in the COPD (44.4%) group (controls 60.4%). ER2223EK lacks in
      any of the study subjects. Further, SNPs did not correlate with COPD severity
      stage (GOLD), exacerbation rates, and clinical course. CONCLUSION: COPD is not
      linked to gene polymorphisms N363S, BCLI-RFLP, and ER2223EK. Since we analyzed
      only these 3 receptor gene polymorphisms, this study cannot rule out that other
      GR gene variants and linkages may be of influence.

PMID- 20156760
TI  - Safety of laboratory analyzers for infection testing - results of the market
      surveillance by the BfArM until End 2007.
AB  - The European Directive 98/79/EC on in vitro diagnostic medical devices (IVD)
      stipulates the marketing and post market surveillance of IVD in the European
      Economic Area. In cases of issues and field corrective actions, the manufacturers
      have to inform the responsible Competent Authorities (CA). In Germany, the
      Federal Institute for Drugs and Medical Devices (BfArM) is the responsible CA for
      most IVD, with a small subset of IVD for immune hematological and infectiological
      testing as well as tissue typing as specified in Annex II of the Directive, being
      within the responsibility of the Paul-Ehrlich-Institute (PEI). In this study, all
      issues regarding laboratory analyzers for infection testing and their
      consumables, but not reagents, kits and general culture media, reported to the
      BfArM between begin 1999 and end of 2007 were analyzed in respect to the sources
      of report, the underlying product failure and the performed corrective actions.
      Within the observation period a total of 1471 reports for IVD were received of
      which 73 related to the IVD for infection testing were included in our study.
      Reports were predominantly received from manufacturers (56) and competent
      authorities (15). Affected products were most frequently those for immunological
      analysis (42) whereas those based on culturing techniques (17) and molecular
      biological techniques (14) played only minor roles. In all these groups,
      laboratory analyzers (55) were more frequently affected than their consumables
      (18). Investigations of the manufacturers were able to identify the underlying
      root causes of product failures in 62 cases (84.9%). In 2 cases (2.7%) the root
      cause remained unclear and in 9 cases (12.3%) a product failure was excluded or a
      user error was the underlying cause. Product failures in laboratory analyzers
      were most frequently caused by software errors (31) and constructional faults (8)
      whereas the predominant cause of product failure in consumables were errors in
      production and quality control (8). Manufacturers issued corrective measures in
      66 cases (90.4%) from which 49 and 17 were related to laboratory analyzers and
      their consumables, respectively. Based on the underlying root causes of product
      failures these were predominantly customer information (48), recalls (40),
      software-updates (30) and design changes (9) in the product group of laboratory
      analyzers as well as customer information (16), recalls (12) and modifications of
      production and quality management (11) in the group of consumables. The results
      and experiences obtained since 1999 suggest that the system for post marketing
      surveillance of IVD is an established tool to ensure product safety, even though
      the current system can be further enhanced.

PMID- 20156761
TI  - Prediction of atopy in the first year of life using cord blood IgE levels and
      family history.
AB  - We assessed correlations of total and specific cord-blood IgE (cIgE) levels with
      allergic symptoms in the first year of life. cIgE levels were determined by an
      immunoassay test in full-term neonates. This is a prospective study in which a
      questionnaire was used after birth, and at 6 and 12 months of age. We used
      multiple logistic regression models to assess the association between the family
      history of atopy and the incidence of allergy. The infants were divided into
      groups based on the cIgE level (Group 1<0.1 IU/ml, n=65; Group 2 0.1-0.5 IU/ml,
      n=63; Group 3 >0.5 IU/ml, n=45). We found the symptoms of atopy in 26 children in
      Group 1 (40%), 30 (47.6%) in Group 2, and 17 (37.7%) in Group 3; the percentage
      of atopic diseases was insignificantly different among the three groups. No
      association between a high total cIgE and specific cIgE with atopy family history
      and the outcome of atopic diseases was discovered. We conclude that neither total
      nor specific cIgE level with atopy family history can be used as an indicator to
      single out high risk infants.

PMID- 20156762
TI  - Total and antigen-specific IGE levels in umbilical cord blood.
AB  - The present study was conducted to learn whether the perinatal and environmental
      factors could influence the total and antigen-specific IgE levels in umbilical
      cord blood. Retrospective data were obtained from 173 mother-infant pairs. Total
      and specific (for children's food, wheat/grass and house dust mite-HDM) cord
      blood IgE levels were determined using the immunoassay test. The total cord blood
      IgE was between 0.0-23.08 IU/ml (mean 0.55 +/-2.07 IU/ml; median 0.16 IU/ml).
      Total IgE levels were significantly higher in boys compared with girls (OR=2.2;
      P=0.007), and in newborns with complicated pregnancy (OR=2.7; P=0.003). A greater
      number of siblings correlated with increases in the total cord blood IgE
      (P<0.02). We detected specific IgE in 34 newborns (40 positive tests). A long
      standing contact with a cat during pregnancy decreased the specific IgE level for
      wheat/grass (OR=3.2; P<0.07) and for children's food (OR=5.0; P<0.04), and the
      contact with a dog decreased the specific-IgE for wheat/grass (OR=0.3; P<0.05).
      Exposure to tobacco smoke correlated with the positive specific IgE toward house
      dust mite (OR=4.7; P=0.005).

PMID- 20156763
TI  - Real-time PCR quantification of plasma DNA in non-small cell lung cancer patients
      and healthy controls.
AB  - INTRODUCTION: Free-circulating DNA is present in minute amounts in plasma of
      healthy individuals, whereas increased levels are found in a number of malignant
      pathologies including non-small cell lung cancer (NSCLC). The objective of this
      research was the evaluation of the plasma DNA quantification capacity to
      distinguish between healthy subjects and non-small cell lung cancer (NSCLC)
      patients. MATERIAL AND METHODS: Plasma samples were collected prospectively from
      16 healthy volunteers and 30 untreated NSCLC patients (I-IIIA). Subsequently,
      free-circulating DNA extraction and quantitative real-time PCR analysis were
      performed. RESULTS: The values of plasma DNA concentration ranged from 0.9 up to
      7.0 ng/ml in healthy individuals and from 1.5 up to 50 ng/ml in NSCLC patients
      before treatment. Cancer group showed several-fold higher mean free-circulating
      DNA concentration than that present in healthy subjects (mean 12.00 vs. 2.65
      ng/ml; P<0.001). A greater variability of plasma DNA concentrations was observed
      in NSCLC patients than in controls (SD 14.50 vs. 2.02, respectively). The area
      under the ROC curve was 0.87 (95% CI, 0.744 to 0.954, P<0.001). CONCLUSION: Non
      small cell lung cancer is associated with elevated levels of cell-free DNA in
      plasma with respect to healthy controls. Real-time PCR method proved its utility
      in effective free-circulating DNA detection and quantification.

PMID- 20156764
TI  - Impairment of the baroreflex control of human respiratory resistance with age.
AB  - BACKGROUND: The mechanism responsible for the central baroreflex resetting with
      age are an area of limited knowledge. We previously demonstrated that in subjects
      aged above 50 the airway resistance did not change in response to baroreceptor
      activation, whereas in younger volunteers the airway resistance significantly
      decreased. OBJECTIVE: The aim of the present study was to evaluate the effect of
      carotid baroreceptor inactivation on the reflex change of respiratory resistance,
      in the course of aging. MATERIAL AND METHODS: 80 healthy men, divided in four
      groups: aged 20-30 (Group I), 31-40 (Group II), 41-50 (Group III), and 51-60
      (Group IV) were included in the study. The selective inactivation of carotid
      baroreceptors was induced by generating a positive pressure of 40 mmHg for 5 s in
      two capsules placed bilaterally on the neck over the bifurcation of the carotid
      arteries. The oscillatory method (Siregnost FD5, Siemens) was used to measure
      continuously respiratory resistance. RESULTS: Inactivation of carotid
      baroreceptors produced a short increase in respiratory resistance by 0.38 +/-
      0.01SE mbar/l/s, i.e., 21.7% above the resting level in Group I and by 0.25 +/-
      0.01 mbar/l/s in Group II. In the two older groups (III and IV) respiratory
      resistance did not change in response to baroreceptors inactivation. CONCLUSIONS:
      In humans aged above 40, carotid baroreceptors do not contribute to
      bronchodilator tone, which causes imbalance between the activities of upper
      airway and chest wall inspiratory muscles leading to a collapsing effect on the
      upper airway.

PMID- 20156765
TI  - Deformation of the nasal septum in children, adolescents, and adults in Western
      Pomerania province of Poland.
AB  - OBJECTIVES: Nasal septum deformation (NSD) contributes to the occurrence of upper
      respiratory tract diseases in around 45-55% of Poland's population. The
      evaluation of frequency of occurrence and type of nasal septum deformation among
      randomly chosen representatives of the Szczecin and surrounding area population
      was the aim of this study. METHODS: NSD was assessed in 235 patients (123 male,
      112 female) aged 5-60. Mladina's classification system was used for the
      evaluation. RESULTS: Deformations of nasal septum were found in 43% of the
      examined subjects. Type 3 of NSD dominated (12.4%), while types 2 and 1 were
      found in 10.3% and 4.2% of the subjects, respectively. 9.2% of the patients
      showed type 5 of deformation, while types 6, 4, and 7 were found in 1.3%, 3.2%
      and 2.7% of the patients, respectively. CONCLUSIONS: Straight nasal septum was
      found in females more often than in males, mostly on the left side. Associations
      between NSD, on one side, and age, sex, and traumas, on the other were found. NSD
      influenced the quality of respiration and frequency of upper respiratory tract
      diseases in the examined subjects.

PMID- 20156766
TI  - Asthma, allergy, mood disorders, and nutrition.
AB  - BACKGROUND: Growing evidence supports comorbidity of asthma and allergies with
      mood disorders and various connections between these diseases. It still remains
      unclear whether this comorbidity is caused by the same pathophysiological factors
      or whether there are other links between asthma and depression. There is no
      definite answer to the question of an optimal treatment to deal with both asthma
      and depression, when they occur simultaneously. Epidemiological and clinical
      trials on the influence of nutrition on certain diseases suggest the effects of
      omega3 polyunsaturated fatty acids (PUFAs) in aiding treatment of mood disorders
      and inflammatory conditions. OBJECTIVE: This is an overview showing the
      connections between asthma, allergic disease, and mood disorders, and the
      influence of nutrition on these conditions. Evidence indicates positive
      correlations between consumption of PUFAs and mood correction. Several analyses
      show the connection between diet and asthma. They may form a basis for potential
      recommending omega3 PUFAs as an adjuvant in prevention and treatment of mental
      disorders, asthma, and allergy.

PMID- 20156767
TI  - Adipocytokines in sleep apnea syndrome.
AB  - OBJECTIVE: Biomarkers of adipose tissue may affect glucose and lipid metabolism
      and present pro-inflammatory properties, thus could be involved in the
      pathobiochemistry of cardiovascular disease (CVD). The coexistence of sleep apnea
      syndrome (OSA) and metabolic risk factors of CVD is worth explaining. The aim of
      the study was to compare the serum adipocytokines in subjects with and without
      OSA, who had all elevated body mass index (BMI). METHODS: Overweight (BMI: 25.0
      29.9 kg/m2) and obese (BMI: 30.0-39.9 kg/m2) OSA-suspected Caucasian males, aged
      30-63, with no acute disease or chronic disorder underwent polysomnographic
      evaluation to select OSA-positive (AHI > or = 5) and OSA-negative (AHI <5)
      subjects. Four subgroups were created of 18 persons each: Over(weight)-OSA-Neg,
      Over-OSA-Pos, Obese-OSA-Neg, Obese-OSA-Pos. In all subjects, plasma carbohydrate
      and lipid metabolism parameters, and serum uric acid, resistin and leptin
      concentrations were determined. RESULTS: A decreased resistin level was observed
      in Over-OSA-Pos vs. Over-OSA-Neg subjects (P=0.037) as well as in Obese-OSA-Pos
      vs. Obese-OSA-Neg (P=0.045). No differences in leptin concentrations were
      observed. A positive correlation between leptin and BMI was in both overweight
      subgroups and a negative one between resistin and fasting glucose was in both
      obese subgroups. CONCLUSIONS: OSA may decrease the serum resistin level in
      subjects with excess body mass and also may contribute to glucose metabolism, but
      has no influence on the leptin level.

PMID- 20156768
TI  - Angiogenic activity of sera from interstitial lung disease patients in relation
      to clinical and radiological changes.
AB  - OBJECTIVE: Clinical symptoms and radiological changes are useful in monitoring
      patients with interstitial lung diseases (ILD). Neovascularization participates
      in the pathogenesis of idiopathic pulmonary fibrosis and other ILD. The objective
      of the study was to examine the relationships between angiogenic activity of sera
      from ILD patients and clinical or radiological status. MATERIAL AND METHODS:
      Serum samples were obtained from 83 patients with sarcoidosis, 31 with idiopathic
      pulmonary fibrosis (IPF), 29 with hypersensitivity pneumonitis (HP), 16 with
      collagen diseases with pulmonary manifestation (CD), 13 with scleroderma (SCL),
      14 with Wegener's granulomatosis (WG), 12 with pulmonary Langerhans cell
      histiocytosis (HIS), 12 with pneumoconiosis (PNC), 10 with drug-induced lung
      disease (DLD), 5 with cryptogenic organizing pneumonia (COP), and from 36 healthy
      volunteers. As an angiogenic test we used a cutaneous angiogenesis assay
      according to Sidky and Auerbach. Clinical status was evaluated using a special
      questionnaire. In all patients chest radiographs were performed. RESULTS: The
      angiogenic properties of sera from ILD differed depending on the clinical
      diagnosis. The strongest proangiogenic effect was induced by sera from patients
      with HP (mean number of new vessels 16.8), CD (16.6), sarcoidosis (16.3), IPF
      (16.2), and PNC (15.7). In the case of DLD (13.2), the effect was comparable to
      healthy controls (13.5). In contrast, sera from SCL (mean number of the vessels
      10.5) and HIS patients (10.8) significantly inhibited angiogenesis compared with
      controls. The angiogenic activity of sera from patients with hilar or mediastinal
      lymph nodes involvement was higher than that of sera from patients with lung
      fibrosis. There were also differences in the serum angiogenic activity in
      relation to the severity of dyspnea. CONCLUSIONS: The data showed that sera from
      ILD patients constitute a source of mediators modulating angiogenesis, but the
      pattern of reaction is different in various diseases. Sera from HP, sarcoidosis,
      IPF, and CD patients demonstrated the strongest proangiogenic activity. However,
      sera from SCL and HIS inhibit angiogenesis. Angiogenic activity of examined sera
      was related to the clinical and radiological changes.

PMID- 20156769
TI  - Co-trimoxazole and prevention of relapses of PR3-ANCA positive vasculitis with
      pulmonary involvement.
AB  - BACKGROUND: Bacterial and viral respiratory tract infections may trigger relapses
      in patients with PR3-positive vasculitis. Data have suggested that treatment with
      co-trimoxazole may be beneficial, because this antibiotic could act by
      eliminating the offending microbe and thereby stopping the initiating stimulus.
      GOAL AND METHODS: Prospective, randomized, placebo-controlled study of the
      efficacy of co-trimoxazole given 960 mg thrice weekly for 18 months in preventing
      relapses in patients with Wegener's granulomatosis (WG) in remission, after
      treatment with cyclophosphamide and prednisolone was conducted. Relapses and
      infections were assessed with predefined criteria based on clinical, laboratory,
      serological, microbiological, and histopathological findings. Sixteen patients
      were assigned to receive co-trimoxazole and 15 to receive placebo. RESULTS:
      Seventy five percent of the patients in the co-trimoxazole group remained in
      remission at 18 months and 55% of those in the placebo group. A proportional
      hazard regression analysis identified a positive PR3-ANCA test at the start of
      treatment, chronic nasal crusting, and Staphylococus aureus infection as risk
      factors for relapse. Furthermore, the analysis identified treatment with co
      trimoxazole as an independent factor associated with prolonged disease-free
      interval. CONCLUSION: Treatment with co-trimoxazole reduces the incidence of
      relapses in patients with Wegener's granulomatosis in remission.

PMID- 20156771
TI  - Dispositional optimism and coping with pain.
AB  - OBJECTIVE: The aim of this article is to analyze the relation between
      dispositional optimism and coping with chronic pain. The study seeks to define
      the relation between life orientation (optimism vs. pessimism) and coping with
      pain (believes about pain control and the choice of coping strategy). MATERIAL
      AND METHODS: The following questionnaires were used: LOT-R - Life Orientation
      Test, BPCQ - The Beliefs about Pain Control Questionnaire and CSQ - The Pain
      Coping Strategies Questionnaire. RESULTS: The results show that dispositional
      optimism correlates positively with: internal locus of pain control r=0.6,
      P<0.01; declared coping with pain r=0.38, P<0.05; diverting attention r = 0.93,
      P<0.01; and behavioral activity r = 0.82, P<0.01. Dispositional optimism
      correlates negatively with catastrophizing r = -0.28, P<0.05. CONCLUSIONS: We
      conclude that dispositional optimism plays a key role in forming the mechanisms
      of coping with chronic pain and thereby in improving the psychophysical comfort
      of patients.

PMID- 20156770
TI  - Clinical implications of serum thrombomodulin in PR3-ANCA-associated vasculitis.
AB  - BACKGROUND: Vascular injury is the main mechanism in pathophysiology of PR3-ANCA
      associated vasculitis. Soluble serum thrombomodulin (sTM) is a membrane-bound
      receptor for thrombin expressed by vascular endothelial cells. - OBJECTIVE: The
      aim of study was to determine the blood levels of sTM in patients with PR3-ANCA
      associated vasculitis. MATERIAL AND METHODS: Twenty five patients with Wegener's
      granulomatosis (WG), 13 with generalized WG and 12 with limited WG, with
      histologically proven disease, and 15 healthy subjects as a control were
      investigated. An ELISA for detection of sTM and PR3-ANCA was performed. The
      disease activity was evaluated according to BVAS and DEI indexes. RESULTS:
      Significant increases in sTM were found in both active generalized and limited
      active WG compared with control values: 108 +/- 12, 56 +/- 2, and 12 +/- 4 ng/ml,
      respectively. Elevated ANCA titer correlated with disease activity, but more
      weakly than sTM levels did. Elevated sTM concentration is a result of vascular
      endothelial injury in the course of PR3-ANCA associated vasculitis. CONCLUSIONS:
      Soluble serum thrombomodulin is a promising, both diagnostic and therapeutic,
      marker of endothelial cell injury in relation to disease activity and progression
      in autoimmune disorders, reflecting the degree of endothelial cell damage.

PMID- 20156772
TI  - Gene polymorphisms of biotransforming enzymes (GSTs) and their association with
      lung cancer in the Slovakian population.
AB  - OBJECTIVE: The aim of present study was to present the results of a case-control
      study focused on genetic polymorphisms of selected Phase II metabolizing enzymes
      (GSTM1, T1, and P1) and to investigate the association of these polymorphisms
      with lung cancer risk in the Slovakian population. MATERIAL AND METHODS: The
      study encompassed 160 lung cancer cases and 220 controls. DNA was extracted from
      peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1
      enzymes were determined by PCR-based methods. We determined the genotype
      distribution of all these genes and their combinations. The association between
      specific genotypes and the development of lung cancer were examined using
      logistic regression analysis to calculate odds ratios (OR) and 95% confidence
      intervals (CI). RESULTS: We found that the GSTM1 null genotype (OR=1.6; 95%
      CI=1.03-2.4; chi(2)=4.08, and P=0.04) was associated with elevated risk. A
      significant correlation also was found for the combined genotypes of GSTM1 null
      and GSTP1 Ile/Val and Val/Val (OR=2.01; 95% CI=1.1-6.1; chi(2)=3.6, and P=0.02)
      and GSTM1 null and GSTT1 positive (OR=2.00; 95% CI=1.2-3.2; chi(2)=7.3, and
      P=0.006). CONCLUSIONS: We conclude that the genotype of metabolizing enzymes and
      allelic combinations underscore the risk for lung cancer. Individual risk
      assessment may be further improved by increasing the number of polymorphisms
      studied and combining them with the traditional epidemiological risk factor.

PMID- 20156773
TI  - Prognostic significance of the hair follicle stem cell marker nestin in patients
      with malignant melanoma.
AB  - Nestin is an intermediate filament protein, and serves as a hair follicle stem
      cell and neural stem cell marker. Recent studies have suggested that nestin
      expression is also important for tumorigenesis. Previous reports from our
      laboratory have revealed that nestin is a marker of HMB-45-negative melanoma
      cells in dermal invasive lesions of nodular malignant melanoma. The present study
      examines nestin expression in malignant melanoma and investigates the
      relationship between nestin expression and prognosis in patients. We
      immunohistochemically stained 78 formalin-fixed and paraffin-embedded malignant
      melanomas for nestin, HMB-45 and S100 reactivity. We found that nestin, HMB-45
      and S100 protein were detected in 56.5%, 88.4% and 100% of malignant melanomas,
      respectively. The 5-year survival rate of stage I and II nestin-positive cases
      was significantly decreased compared to the nestin-negative cases (p < 0.05). In
      addition, the 5-year survival rate exceeded 80% in nestin-negative malignant
      melanomas at all stages of tumor development. We conclude that nestin expression
      may be a predictor of poor prognosis in patients with malignant melanoma.

PMID- 20156774
TI  - AEC syndrome caused by heterozygous mutation in the SAM domain of p63 gene.

PMID- 20156775
TI  - The Purple Clinical Series: a useful tool for clinical oncologists to tackle
      current hot spots in cancer.

PMID- 20156776
TI  - A summary in time.

PMID- 20156777
TI  - Non-small-cell lung cancer harbouring mutations in the EGFR kinase domain.
AB  - Key "driver" mutations have been discovered in specific subgroups of non-small
      cell lung cancer (NSCLC) patients. Activating mutations in the form of deletions
      in exon 19 (del 19) or the missense mutation L858R in the tyrosine kinase domain
      of the epidermal growth factor receptor (EGFR) predict outcome to EGFR tyrosine
      kinase inhibitors (TKIs) such as gefitinib and erlotinib. Pooled data from
      several phase II studies show that gefitinib and erlotinib induce responses in
      over 70% of NSCLC patients harbouring EGFR mutations, with progression-free
      survival (PFS) ranging from 9 to 13 months and median survival of around 23
      months. Two studies in Caucasian and Asian patients have confirmed that these
      subgroups of patients attain response rates of 70% with erlotinib and ge-
      fitinib, including complete responses, PFS up to 14 months and median survival up
      to 27 months. These landmark outcomes have been accompanied by new challenges:
      the additional role of chemotherapy and the management of tumours with the
      secondary T790M mutation that confers resistance to EGFR TKIs. Mechanisms of
      resistance to reversible EGFR TKIs should be further clarified and could be
      related to modifications in DNA repair. The presence of double mutations (T790M
      plus either L858R or del 19) at the time of diagnosis could be much more frequent
      than originally thought. The sensitivity to EGFR TKIs could be greatly influenced
      by the expression of genes involved in the repair of DNA double-strand breaks by
      homologous recombination and non-homologous end joining.

PMID- 20156778
TI  - Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis,
      prevention and treatment strategies.
AB  - Chemotherapy-induced peripheral neuropathy (CIN) is a common toxicity of
      anticancer treatment and its incidence is growing. It significantly affects
      quality of life and is a dose-limiting factor that interferes with treatment. Its
      diagnosis can be established in clinical terms but some complementary tests can
      help when the diagnosis is difficult. There is still no proven method to prevent
      it that has become a standard of care in spite of the huge amount of
      investigation carried out in recent years. There are promising strategies that
      could help reduce the burden of this complication. This review will suggest an
      approach to the diagnosis of these disorders and provide an update on new
      therapies.

PMID- 20156779
TI  - Biomarkers in bronchopulmonary cancer.
AB  - Non-small-cell lung cancer (NSCLC) ranks among the neoplasms with the worst
      prognoses and the highest mortality rates. Several factors, mainly clinical, are
      known that provide a predictive value on the course of the disease. In the era in
      which we live, the molecular basis of cancer is studied in depth and several
      molecular markers have been described that could play a prognostic role or that
      could predict the probability of responding to the different treatments used.
      Moreover, some mechanisms have been proposed that could explain primary or
      acquired resistance to treatment with chemotherapy and to targeted therapies.
      Knowing all these pathways is very important, as it allows the development of
      selective therapeutic strategies that minimise toxicity and optimise treatment
      effectiveness. However, the data obtained yield results that are at times
      contradictory, prospective studies with biomarkers thus being necessary so that
      their role can be established with the necessary evidence.

PMID- 20156780
TI  - Gastrointestinal stromal tumours at present: an approach to burning questions.
AB  - Because of their well known origin in gene mutations and a revolutionary therapy
      by means of molecular targets, gastrointestinal stromal tumours (GIST) constitute
      a plentiful and paradigmatic model of translational investigation, resulting in
      an avalanche of exponential growth data. In this article, we focus on what we
      consider to be hot spots in GIST at present. A wide spectrum of events is
      approached, extending from subtle pathogenic mechanisms at a molecular level
      (gene mutations and their implications for cell receptors with subsequent
      activation of signalling pathways) to more practical problems facing diagnosis
      (molecular markers, role of biopsy), prognosis (risk stratification systems) and
      different therapeutic aspects (laparoscopic surgery, role of surgery in advanced
      disease, response criteria, adjuvant and neoadjuvant therapy, treatment for
      progressing and recurrent disease, therapy directed on mutation analysis and new
      developments, among others). The review has been endorsed by level of evidence
      evaluation through a recognised pattern to assist in teaching, and a final
      summary of recommendations and a management algorithm are included.

PMID- 20156782
TI  - Breast Cancer OncoGuia: surgical pathology report guidelines.

PMID- 20156783
TI  - Circulating tumour cell analysis as an early marker for relapse in stage II and
      III colorectal cancer patients: a pilot study.
AB  - INTRODUCTION: Recent studies have identified both the prognostic and predictive
      utility of determining the number of circulating tumour cells (CTC) in patients
      with solid cancers. MATERIAL AND METHODS: In the present pilot study we evaluated
      the ability of two different methods to isolate CTC in combination with two
      strategies to enumerate CTC from patients with stages II and III surgically
      treated colorectal cancer (CRC). First, we used two systems for tumour cell
      enrichment (differential centrifugation and immunomagnetic beads), combined with
      two methods to enumerate CTC (real-time PCR and fl ow cytometry), to determine
      the most efficient combination. These experiments were performed in a model
      system using serial dilutions of HT29 tumour cell lines with lymphocytes. Then,
      CTC analysis using the technical approach selected before was performed in 109
      blood samples from 16 stage II and III CRC patients during chemotherapy treatment
      and follow-up. RESULTS: Immunomagnetic beads followed by flow cytometry was the
      most efficient combination (ED=60.53; p=0.5). Two cases out of 16 patients
      analysed had clinical tumour relapse. In both, we detected a significant increase
      of CTC five and six months, respectively, before the relapse was clinically
      evidenced. An increase of CTC was also observed in another case without clinical
      evidence of relapse. The remaining cases (13) had very few or no detectable CTC
      and no clinical evidence of relapse (p=0.029). CONCLUSIONS: Changes in CTC
      numbers during follow-up might predict tumour relapse. Further evaluation of CTC
      prognostic and predictive value in patients with early CRC is warranted.

PMID- 20156784
TI  - Mixed paratesticular liposarcoma with osteosarcoma elements.
AB  - Spermatic cord sarcomas (SCS) are very infrequent and sometimes misdiagnosed
      malignancies. Moreover, their optimal management remains undefined with ongoing
      controversy about the indications for adjuvant therapy. Histologically,
      liposarcomas are the most common type. Osteosarcoma is rarely observed in this
      location and combined tumours with this component have not been described. We
      present a case of SCS with mixed differentiation with both liposarcoma and
      osteosarcoma elements.

PMID- 20156781
TI  - Breast Cancer OncoGuia.

PMID- 20156785
TI  - Rectal metastasis from lobular breast carcinoma 15 years after primary diagnosis.
AB  - Lobular breast carcinoma represents 2-20% of infiltrative carcinomas of the
      breast. The incidence of extrahepatic gastrointestinal (GI) tract metastases
      observed in necropsy studies varies from 6% to 18% and the most commonly affected
      organ is the stomach, followed by colon and rectum [1-4]. Reported herein is the
      case of a 67-year-old woman who was primarily diagnosed and surgically treated
      for a lobular carcinoma of the breast 15 years ago and is now referred with back
      pain and right hydronephrosis caused by a metastasis in rectum. Frequently, the
      absence of specific symptoms of digestive metastases of breast cancer leads to a
      misdiagnosis of this pathology [5-7]. The treatment will be based on a detailed
      clinical history and histopathological findings. Metastases from breast cancer in
      GI tract tumours must be excluded in a patient with previous history of breast
      carcinoma, as in the case reported herein.

PMID- 20156786
TI  - Cranial metastases: first sign of colorectal cancer. Is the resection of the
      primary non-complicated tumour indicated when the metastases have been resected?

PMID- 20156787
TI  - [Repeat resection of the liver--a challenge in modern oncologic surgery].
AB  - Surgical and oncological treatment of liver metastases of CRC has made a
      significant progress in the last twenty years. Although chemotherapy has
      developed enormously, only successfully resected (R0) patients may hope a long
      term survival. The almost 60% recurrence rate after resection is a significant
      challenge. Authors review patients data operated at the Surgical Department of
      Uzsoki Teaching Hospital between 1995 and 2008 with hepatic metastases of
      colorectal origin. Oncological and surgical principles are summarized in the
      sight of the recent literature review and authors own experience with repeat
      hepatic resection. Recent literature data demonstrate--which is confirmed by our
      experience--that R0 resection of recurrent hepatic metastases provides similar
      overall 5 year survival rate than that of patients who underwent a single
      resection only. In the case of recurrent CLM, the oncoteam should prepare a
      surgically resectable situation.

PMID- 20156788
TI  - Endo-anal ultrasound versus endo-anal magnetic resonance imaging for the
      depiction of external anal sphincter pathology in patients with faecal
      incontinence: a systematic review.
AB  - OBJECTIVE: To evaluate the endo-anal ultrasound (EAUS) versus endo-anal magnetic
      resonance imaging (EAMRI) in the diagnosis of external anal sphincter defects
      (EAS) in patients with faecal incontinence (FI). METHODS: Studies on EAUS and
      EAMRI were selected and analyzed to generate summative data. RESULTS: Five
      studies encompassing 347 patients of FI were included in this review. Three
      studies validated the results of EAUS and EAMRI by surgery (61 patients). In the
      fixed effect model, EAUS was superior to EAMRI in the depiction of EAS defects.
      On combined analysis of five studies using fixed effect model, both EAUS and
      EAMRI were equally effective. However, there was a significant heterogeneity
      between studies. CONCLUSION: EAUS and EAMRI are comparable in the diagnosis of
      EAS defects in patients of FI. Since EAUS is an economical, quicker and easily
      available imaging modality, it may be used a preferable investigation for the
      diagnosis of EAS defects in patients of FI.

PMID- 20156789
TI  - [Investigation of surgical applicability of acryl-based tissue expanders].
AB  - INTRODUCTION: Hydrogels made of acrylamide (AAm), acrylic acid (AAc) and N
      isopropylacrylamide (NIPAAm) display outstanding ability of swelling in vitro and
      this property can be influenced by the composition of the polymers. Our objective
      was to study the in vivo behavior of hydrogels made of acrylics and their
      potential role in surgery. MATERIALS AND METHODS: Cylinder-shaped hydrogels were
      implanted under the skin of rats in the dorsal region. In group 1 AAm, in group 2
      AAc while in group 3 NIPAAm expanders were applied. The observation period lasted
      18 days, during this time the length and the diameter of the hydrogels were
      measured daily. After removal of the polymers the moisture mass and the
      rheological parameters were determined. Furthermore, biopsies were taken from
      adjacent tissues. RESULTS: Expanders achieved the peak of swelling in two weeks.
      During the observation period their mass significantly increased. NIPAAm polymers
      demonstrated the highest tendency to retain their preformed shape. Histological
      analysis revealed that implantation of AAc devices was associated with serious
      tissue damage while healthy skin was harvested with the other two polymers.
      CONCLUSION: In conclusion, NIPAAm hydrogel seems to be the most promising
      candidate for surgical utilization.

PMID- 20156790
TI  - [Laparoscopic cholecystectomy in totalis situs inversus for cholecystitis].
AB  - Various congenital anomalies, organ transpositions impose special demands on
      building up the diagnosis; the mirror image of the abdominal organs tests the
      skills of the surgeon. We report a case of a 68 year old female patient, with a
      known situs inversus totalis, who underwent a laparoscopic cholecystectomy. We
      discuss our diagnostic steps (such as US, ERCP and EST), the variation of
      maneuvers used during the operation. No iatrogenic event occurred. We also stress
      that the surgeon should be alert of possible local anatomic variations and, if
      needed, conversion should be a solution of choice.

PMID- 20156791
TI  - [Pectoral major muscle-sling flap for treatment of recurrent subareolar abscess:
      a new surgical technique].
AB  - Recurrent subareolar abscess is an uncommon benign disease of the breast, which
      is caused by peri-ductal mastitis with various etiology. Radical surgical
      procedure is necessary for cure instead of inadequate courses of antibiotics or
      incisions. In some cases the use of the pectoral muscle sling flap can be an
      alternative technique for the treatment of recurrent subareolar abscess after
      repeated standard surgical treatment. A 36 year old woman, who successfully
      underwent this procedure, is presented here.

PMID- 20156792
TI  - [One-stage bilateral vats-sympathectomy for the treatment of severe upper body
      hyperhidrosis].
AB  - Thoracoscopic sympathectomy (VATS) is routinely used to treat severe palmar and
      axillary hyperhydrosis. The authors present a novel method: one-stage bilateral
      VATS-sympathectomy. Special considerations also discussed regarding the
      anaesthesia and operative technique of the procedure. The history of surgical
      therapy of hyperhidrosis is reviewed briefly, too. The authors conclude that one
      stage bilateral VATS-sympathectomy for palmar and axillary severe hyperhidrosis
      is a safe and effective method, patient satisfaction improves and cost is
      significantly decreased due to shorter hospital stay.

PMID- 20156793
TI  - [Is there any hope?].

PMID- 20156794
TI  - [Comments on "Is there any hope?" by Csaba Gaal].

PMID- 20156796
TI  - [Letter to the Editor: Surgery in China].

PMID- 20156801
TI  - Detection of mutations in the FemXAB protein family in oxacillin-susceptible mecA
      positive Staphylococcus aureus clinical isolates.
AB  - Objectives Methicillin-resistant Staphylococcus aureus (MRSA) strains that
      express the mecA gene but are oxacillin susceptible (OS-MRSA; oxacillin MIC </=2
      mg/L) are increasingly reported. To gain molecular and functional insights on
      this observation, we focused on additional factors possibly contributing to
      phenotypic susceptibility. Methods The nucleotide content of mecA, femA, femB and
      femX genes, which are considered essential for methicillin resistance, was
      determined in four OS-MRSA clinical isolates and a genetically similar low-level
      MRSA control (oxacillin MIC 6 mg/L). Gene expression was quantified compared with
      the low- and a high-level MRSA (MIC 256 mg/L) control. The tertiary structure of
      Fem proteins was predicted based on protein structure homology modelling, using
      web-based automated comparative protein modelling. Growth kinetics were tested
      for the study and control isolates, to determine whether FemXAB mutations lead to
      reduced fitness. Results Genes mecA, femA, femB and femX were expressed similarly
      in the study and the control isolates. Mutations in the gene mecA were not
      present in any isolate. However, several mutations leading to amino acid
      substitutions in positions possibly affecting Fem enzyme activity were detected
      in all fem genes. Two OS-MRSA that had no oxacillin heteroresistance had more
      mutations in the Fem proteins compared with the remaining isolates that were
      heteroresistant. The low-level MRSA control had considerably fewer mutations. No
      differences between growth rates of the OS-MRSA and the MRSA controls were
      observed. Conclusions Accumulation of amino acid changes in Fem proteins might
      affect intact cell wall synthesis, even though not causing reduced viability,
      thus contributing to atypical oxacillin responsiveness.

PMID- 20156802
TI  - Enzastaurin plus temozolomide with radiation therapy in glioblastoma multiforme:
      a phase I study.
AB  - We conducted a phase I study to determine the safety and recommended phase II
      dose of enzastaurin (oral inhibitor of the protein kinase C-beta [PKCbeta] and
      the PI3K/AKT pathways) when given in combination with radiation therapy (RT) plus
      temozolomide to patients with newly diagnosed glioblastoma multiforme or
      gliosarcoma. Patients with Karnofsky performance status > or =60 and no enzyme
      inducing anti-epileptic drugs received RT (60 Gy) over 6 weeks, concurrently with
      temozolomide (75 mg/m(2) daily) followed by adjuvant temozolomide (200 mg/m(2))
      for 5 days/28-d cycle. Enzastaurin was given once daily during RT and adjuvantly
      with temozolomide; the starting dose of 250 mg/d was escalated to 500 mg/d if <
      or =1/6 patients had dose-limiting toxicity (DLT) during RT and the first
      adjuvant cycle. Patients continued treatment for 12 adjuvant cycles unless
      disease progression or unacceptable toxicity occurred. Twelve patients enrolled.
      There was no DLT in the first 6 patients treated with 250 mg enzastaurin. At 500
      mg, 2 of 6 patients experienced a DLT (1 Grade 4 and 1 Grade 3 thrombocytopenia).
      The patient with Grade 3 DLT recovered to Grade <1 within 28 days and adjuvant
      temozolomide and enzastaurin was reinitiated with dose reductions. The other
      patient recovered to Grade <1 toxicity after 28 days and did not restart
      treatment. Enzastaurin 250 mg/d given concomitantly with RT and temozolomide and
      adjuvantly with temozolomide was well tolerated and is the recommended phase II
      dose. The proceeding phase II trial has finished accrual and results will be
      reported in 2009.

PMID- 20156803
TI  - Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human
      glioblastoma.
AB  - The phosphatidylinositol-3-kinase (PI3K)/Akt oncogenic pathway is critical in
      glioblastomas. Loss of PTEN, a negative regulator of the PI3K pathway or
      activated PI3K/Akt pathway that drive increased proliferation, survival,
      neovascularization, glycolysis, and invasion is found in 70%-80% of malignant
      gliomas. Thus, PI3K is an attractive therapeutic target for malignant glioma. We
      report that a new irreversible PI3K inhibitor, PX-866, shows potent inhibitory
      effects on the PI3K/Akt signaling pathway in glioblastoma. PX-866 did not induce
      any apoptosis in glioma cells; however, an increase in autophagy was observed. PX
      866 inhibited the invasive and angiogenic capabilities of cultured glioblastoma
      cells. In vivo, PX-866 inhibited subcutaneous tumor growth and increased the
      median survival time of animals with intracranial tumors. We also assessed the
      potential of proton magnetic resonance spectroscopy (MRS) as a noninvasive method
      to monitor response to PX-866. Our findings show that PX-866 treatment causes a
      drop in the MRS-detectable choline-to-NAA, ratio and identify this partial
      normalization of the tumor metabolic profile as a biomarker of molecular drug
      action. Our studies affirm that the PI3K pathway is a highly specific molecular
      target for therapies for glioblastoma and other cancers with aberrant PI3K/PTEN
      expression.

PMID- 20156804
TI  - Overexpression of ezrin inactivates NF2 tumor suppressor in glioblastoma.
AB  - Glioblastoma is a frequent brain malignancy with a dismal prognosis. The
      molecular changes causing its aggressive phenotype are under investigation. We
      report that the cytoskeletal-related proteins neurofibromatosis type 2 (NF2) and
      ezrin have opposite yet interdependent activities in glioblastoma growth. We show
      that NF2 is absent in approximately one-third of glioblastoma cell lines and
      tumors, and that it suppresses growth when expressed in cells. Although ezrin
      overexpression was previously observed in glioblastoma, we show here that ezrin
      enhanced cell proliferation and anchorage-independent growth but only in cells
      expressing NF2. Ezrin interacted and delocalized NF2 from the cortical
      compartment releasing its inhibition on Rac1. By using swap NF2-ezrin molecules,
      we identified that the opposite effects on cell growth of NF2 and ezrin depend on
      their amino-terminal FERM domain. The subcellular cortical localization appeared
      important for NF2 suppressive activity. In contrast, the ability of ezrin to
      enhance growth or complex NF2 did not depend on the molecular conformation or
      subcellular localization. In conclusion, these studies show 2 mechanisms for NF2
      inactivation in glioblastoma: (i) decreased protein expression and (ii)
      increasing dosages of ezrin that disable NF2 by intermolecular association and
      aberrant intracellular recruitment.

PMID- 20156805
TI  - Loss of 1p, 19q, and 10q heterozygosity prospectively predicts prognosis of
      oligodendroglial tumors--towards individualized tumor treatment?
AB  - The purpose of this study was to determine whether chromosome 10q loss is a
      predictor of tumor aggressiveness and poor clinical outcome in patients with
      oligodendroglial tumors alone or together with loss of heterozygosity (LOH) on
      chromosomes 1p and 19q. A microsatellite analysis was performed on sections from
      130 patients with grade II and grade III oligodendroglial tumors to assess the
      allelic status of chromosomes 1p, 19q, and 10q, plus detailed clinical and
      radiological information was taken prospectively. Median age at diagnosis was
      45.5 years. Seventy-eight patients had disease progression after initial therapy;
      median progression-free survival (PFS) was 27.5 months. Age <47 years,
      postoperative Karnofsky performance score >65, no contrast enhancement on MRI,
      grade II, and complete removal on surgery were significantly correlated with a
      better PFS. Median overall survival (OS) was 40.5 months. Pure oligodendroglioma
      and temozolomide chemotherapy were correlated with better OS. 10q LOH was
      correlated with anaplastic grade and 1p19q LOH correlated with pure
      oligodendroglioma. There was a significant association between LOH status and the
      tumors' response to chemotherapy: 92.3% with 1p19q LOH, 83.3% without allelic
      losses, 50% with 1p19q10q LOH, and 14.5% with 10q LOH. Patients with 10q LOH
      alone had PFS of 6 months and a 3-year survival rate of 1%, when compared with 36
      months and 85%, respectively, in patients with 1p19q LOH but without 10q LOH. 1p
      loss was correlated with better PFS (P < .005) and OS (P = .0007), whereas 10q
      loss was correlated with decreased PFS (P < .0001) and OS (P < .0001). 10q LOH
      predicted a survival disadvantage in patients with oligodendroglial tumors
      irrespective of 1p/19q LOH status.

PMID- 20156806
TI  - Adjuvant whole-brain radiation therapy after surgical resection of single brain
      metastases.
AB  - Adjuvant whole-brain radiation therapy (WBRT) after resection of single brain
      metastases remains controversial. Despite a phase III trial to the contrary,
      clinicians often withhold WBRT after resection of single brain metastases based
      on the argument that available evidence does not inform regarding treatment of
      all patients, such as those with radioresistant tumors. However, there is limited
      information about whether subpopulations benefit equally from WBRT after
      resection. Therefore, we undertook a retrospective study to determine the
      clinical, radiographic, and histologic features that influenced the effectiveness
      of adjuvant WBRT. We reviewed 358 patients with newly diagnosed, single brain
      metastases, who underwent resection, of which 142 (40%) received adjuvant WBRT
      and 216 (60%) did not. Median follow-up was 60.1 months. There were multiple
      tumor histologies, including 197 (55%) "radiosensitive" and 161 (45%)
      "radioresistant" tumors. Compared with observation, WBRT significantly reduced
      recurrence both locally (HR = 0.58; 95% CI 0.35-0.98, P = .04) and at distant
      brain sites (HR = 0.43, 95% CI 0.30-0.61, P < .001). Multivariate analyses
      demonstrated that withholding WBRT was an independent predictor of local and
      distant recurrence. For local recurrence, tumors with a maximum diameter of >=3
      cm that did not receive adjuvant WBRT had an increased risk of recurring locally
      (HR = 3.14, 95% CI 1.02-9.69, P = .05). For distant recurrence, patients whose
      primary disease was progressing and who did not receive WBRT had an increased
      risk of distant recurrence (HR = 2.16, 95% CI 1.01-4.66, P = .05). There was no
      effect of WBRT based on tumor type. Adjuvant WBRT significantly reduces local and
      distant recurrences in subsets of patients, particularly those with metastases >3
      cm or with active systemic disease.

PMID- 20156807
TI  - A 3-dimensional extracellular matrix as a delivery system for the transplantation
      of glioma-targeting neural stem/progenitor cells.
AB  - Neural stem/progenitor cells (NSPCs) display inherent pathotropic properties that
      can be exploited for targeted delivery of therapeutic genes to invasive
      malignancies in the central nervous system. Optimizing transplantation efficiency
      will be essential for developing relevant NSPC-based brain tumor therapies. To
      date, the real-world issue of handling and affixing NSPCs in the context of the
      neurosurgical resection cavity has not been addressed. Stem cell transplantation
      using biocompatible devices is a promising approach to counteract poor NSPC graft
      survival and integration in various types of neurological disorders. Here, we
      report the development of a 3-dimensional substrate that is based on
      extracellular matrix purified from tissue-engineered skin cultures (3DECM). 3DECM
      enables the expansion of embedded NSPCs in vitro while retaining their
      uncommitted differentiation status. When implanted in intracerebral glioma
      models, NSPCs were able to migrate out of the 3DECM to targeted glioma growing in
      the contralateral hemisphere, and this was more efficient than the delivery of
      NSPC by intracerebral injection of cell suspensions. Direct application of a
      3DECM implant into a tumor resection cavity led to a marked NSPC infiltration of
      recurrent glioma. The semisolid consistency of the 3DECM implants allowed simple
      handling during the surgical procedure of intracerebral and intracavitary
      application and ensured continuous contact with the surrounding brain parenchyma.
      Here, we demonstrate proof-of-concept of a matrix-supported transplantation of
      tumor-targeting NSPC. The semisolid 3DECM as a delivery system for NSPC has the
      potential to increase transplantation efficiency by reducing metabolic stress and
      providing mechanical support, especially when administered to the surgical
      resection cavity after brain tumor removal.

PMID- 20156808
TI  - Bevacizumab salvage therapy following progression in high-grade glioma patients
      treated with VEGF receptor tyrosine kinase inhibitors.
AB  - Agents targeting the vascular endothelial growth factor (VEGF) pathway are being
      used with increasing frequency in patients with recurrent high-grade glioma. The
      effect of more than one antiangiogenic therapy given in succession has not been
      established. We reviewed the efficacy of bevacizumab, a VEGF-A monoclonal
      antibody, in patients who progressed following prior therapy with VEGF receptor
      tyrosine kinase inhibitors (R-TKi). Seventy-three patients with recurrent high
      grade gliomas received VEGF R-TKi (cediranib, sorafenib, pazopanib, or sunitinib)
      as part of phase I or II clinical trials. Twenty-four of these patients with
      glioblastoma progressed and received bevacizumab-containing regimens immediately
      after R-TKi. Those who stopped R-TKi therapy for reasons other than disease
      progression, or received a treatment that did not include bevacizumab, were
      excluded from the analysis. The efficacy of bevacizumab-containing regimens in
      these 24 patients was evaluated. During R-TKi therapy, 6 of 24 patients (25%) had
      a partial response (PR) to treatment. The 6-month progression-free survival
      (APF6) was 16.7% and median time-to-progression (TTP) was 14.3 weeks. Grade
      III/IV toxicities were seen in 13 of 24 patients (54%). Subsequently with
      bevacizumab salvage therapy, 5 of 24 patients (21%) had a PR, the APF6 was 12.5%,
      and the median TTP was 8 weeks. Five of 24 patients had grade III/IV toxicities
      (21%). The median overall survival (OS) from the start of R-TKi therapy was 9.2
      months (range: 2.8-34.1+), whereas the median OS after bevacizumab was 5.2 months
      (range: 1.3-28.9+). Bevacizumab retains modest activity in high-grade glioma
      patients who progress on R-TKi. However, the APF6 of 12.5% in this cohort of
      patients indicates that durable tumor control is not achieved for most patients.

PMID- 20156809
TI  - Activating mutations in BRAF characterize a spectrum of pediatric low-grade
      gliomas.
AB  - In the present study, DNA from 27 grade I and grade II pediatric gliomas,
      including ganglioglioma, desmoplastic infantile ganglioglioma, dysembryoplastic
      neuroepithelial tumor, and pleomorphic xanthoastrocytoma was analyzed using the
      Illumina 610K Beadchip SNP-based oligonucleotide array. Several consistent
      abnormalities, including gain of chromosome 7 and loss of 9p21 were observed.
      Based on our previous studies, in which we demonstrated BRAF mutations in 3
      gangliogliomas, 31 tumors were screened for activating mutations in exons 11 and
      15 of the BRAF oncogene or a KIAA1549-BRAF fusion product. There were no cases
      with a KIAA1549-BRAF fusion. A BRAF V600E mutation was detected in 14 of 31
      tumors, which was not correlated with any consistent pattern of aberrations
      detected by the SNP array analysis. Tumors were also screened for mutations in
      codon 132 in exon 4 of IDH1, exons 2 and 3 of KRAS, and exons 2-9 of TP53. No
      mutations in KRAS or TP53 were identified in any of the samples, and there was
      only 1 IDH1 R132H mutation detected among the sample set. BRAF mutations
      constitute a major genetic alteration in this histologic group of pediatric brain
      tumors and may serve as a molecular target for biologically based inhibitors.

PMID- 20156810
TI  - Genetics of aneurysmal disease: the dogs that did not bark.

PMID- 20156811
TI  - Association study of single nucleotide polymorphisms on chromosome 19q13 with
      abdominal aortic aneurysm.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex disorder in which
      environmental and genetic factors play a role in pathogenesis. Linkage to 2
      adjacent loci on 19q13 in familiar AAA was previously demonstrated. We studied
      whether genetic variation within these regions predisposes to AAA. METHODS:
      Common genetic variants in the described regions on 19q13 were analyzed using tag
      single nucleotide polymorphisms (SNPs) in a Dutch case-control population. Single
      nucleotide polymorphism genotyping was performed in a 2-stage approach. RESULTS:
      In stage 1, 615 SNPs were genotyped in 376 AAA patients and 648 controls. In
      stage 2, 8 SNPs of stage 1 with a P value < .015 were genotyped in a second
      independent cohort of 360 cases and 376 controls. No differences in allele
      frequencies were observed. CONCLUSION: Our findings suggest that there are no
      common AAA predisposing SNPs within the 19q13 loci. Hence, the genetic basis of
      familiar and sporadic AAA may differ.

PMID- 20156812
TI  - Integrating ecology, psychology and neurobiology within a food-hoarding paradigm.
AB  - Many animals regularly hoard food for future use, which appears to be an
      important adaptation to a seasonally and/or unpredictably changing environment.
      This food-hoarding paradigm is an excellent example of a natural system that has
      broadly influenced both theoretical and empirical work in the field of biology.
      The food-hoarding paradigm has played a major role in the conceptual framework of
      numerous fields from ecology (e.g. plant-animal interactions) and evolution (e.g.
      the coevolution of caching, spatial memory and the hippocampus) to psychology
      (e.g. memory and cognition) and neurobiology (e.g. neurogenesis and the
      neurobiology of learning and memory). Many food-hoarding animals retrieve caches
      by using spatial memory. This memory-based behavioural system has the inherent
      advantage of being tractable for study in both the field and laboratory and has
      been shaped by natural selection, which produces variation with strong fitness
      consequences in a variety of taxa. Thus, food hoarding is an excellent model for
      a highly integrative approach to understanding numerous questions across a
      variety of disciplines. Recently, there has been a surge of interest in the
      complexity of animal cognition such as future planning and episodic-like-memory
      as well as in the relationship between memory, the environment and the brain. In
      addition, new breakthroughs in neurobiology have enhanced our ability to address
      the mechanisms underlying these behaviours. Consequently, the field is
      necessarily becoming more integrative by assessing behavioural questions in the
      context of natural ecological systems and by addressing mechanisms through
      neurobiology and psychology, but, importantly, within an evolutionary and
      ecological framework. In this issue, we aim to bring together a series of papers
      providing a modern synthesis of ecology, psychology, physiology and neurobiology
      and identifying new directions and developments in the use of food-hoarding
      animals as a model system.

PMID- 20156813
TI  - The history of scatter hoarding studies.
AB  - In this review, I will present an overview of the development of the field of
      scatter hoarding studies. Scatter hoarding is a conspicuous behaviour and it has
      been observed by humans for a long time. Apart from an exceptional experimental
      study already published in 1720, it started with observational field studies of
      scatter hoarding birds in the 1940s. Driven by a general interest in birds,
      several ornithologists made large-scale studies of hoarding behaviour in species
      such as nutcrackers and boreal titmice. Scatter hoarding birds seem to remember
      caching locations accurately, and it was shown in the 1960s that successful
      retrieval is dependent on a specific part of the brain, the hippocampus. The
      study of scatter hoarding, spatial memory and the hippocampus has since then
      developed into a study system for evolutionary studies of spatial memory. In
      1978, a game theoretical paper started the era of modern studies by establishing
      that a recovery advantage is necessary for individual hoarders for the evolution
      of a hoarding strategy. The same year, a combined theoretical and empirical study
      on scatter hoarding squirrels investigated how caches should be spaced out in
      order to minimize cache loss, a phenomenon sometimes called optimal cache density
      theory. Since then, the scatter hoarding paradigm has branched into a number of
      different fields: (i) theoretical and empirical studies of the evolution of
      hoarding, (ii) field studies with modern sampling methods, (iii) studies of the
      precise nature of the caching memory, (iv) a variety of studies of caching memory
      and its relationship to the hippocampus. Scatter hoarding has also been the
      subject of studies of (v) coevolution between scatter hoarding animals and the
      plants that are dispersed by these.

PMID- 20156814
TI  - Using ecology to guide the study of cognitive and neural mechanisms of different
      aspects of spatial memory in food-hoarding animals.
AB  - Understanding the survival value of behaviour does not tell us how the mechanisms
      that control this behaviour work. Nevertheless, understanding survival value can
      guide the study of these mechanisms. In this paper, we apply this principle to
      understanding the cognitive mechanisms that support cache retrieval in scatter
      hoarding animals. We believe it is too simplistic to predict that all scatter
      hoarding animals will outperform non-hoarding animals on all tests of spatial
      memory. Instead, we argue that we should look at the detailed ecology and natural
      history of each species. This understanding of natural history then allows us to
      make predictions about which aspects of spatial memory should be better in which
      species. We use the natural hoarding behaviour of the three best-studied groups
      of scatter-hoarding animals to make predictions about three aspects of their
      spatial memory: duration, capacity and spatial resolution, and we test these
      predictions against the existing literature. Having laid out how ecology and
      natural history can be used to predict detailed cognitive abilities, we then
      suggest using this approach to guide the study of the neural basis of these
      abilities. We believe that this complementary approach will reveal aspects of
      memory processing that would otherwise be difficult to discover.

PMID- 20156815
TI  - What scatter-hoarding animals have taught us about small-scale navigation.
AB  - Many animals use cues for small-scale navigation, including beacons, landmarks,
      compasses and geometric properties. Scatter-hoarding animals are a unique system
      to study small-scale navigation. They have to remember and relocate many
      individual spatial locations, be fairly accurate in their searching and have to
      remember these locations for long stretches of time. In this article, we review
      what is known about cue use in both scatter-hoarding birds and rodents. We
      discuss the importance of local versus global cues, the encoding of bearings and
      geometric rules, the use of external compasses such as the Sun and the influence
      of the shape of experimental enclosures in relocating caches or hidden food.
      Scatter-hoarding animals are highly flexible in how and what they encode. There
      also appear to be differences in what scatter-hoarding birds and rodents encode,
      as well as what scatter-hoarding animals in general encode compared with other
      animals. Areas for future research with scatter-hoarding animals are discussed in
      light of what is currently known.

PMID- 20156816
TI  - Is bigger always better? A critical appraisal of the use of volumetric analysis
      in the study of the hippocampus.
AB  - A well-developed spatial memory is important for many animals, but appears
      especially important for scatter-hoarding species. Consequently, the scatter
      hoarding system provides an excellent paradigm in which to study the integrative
      aspects of memory use within an ecological and evolutionary framework. One of the
      main tenets of this paradigm is that selection for enhanced spatial memory for
      cache locations should specialize the brain areas involved in memory. One such
      brain area is the hippocampus (Hp). Many studies have examined this adaptive
      specialization hypothesis, typically relating spatial memory to Hp volume.
      However, it is unclear how the volume of the Hp is related to its function for
      spatial memory. Thus, the goal of this article is to evaluate volume as a main
      measurement of the degree of morphological and physiological adaptation of the Hp
      as it relates to memory. We will briefly review the evidence for the
      specialization of memory in food-hoarding animals and discuss the philosophy
      behind volume as the main currency. We will then examine the problems associated
      with this approach, attempting to understand the advantages and limitations of
      using volume and discuss alternatives that might yield more specific hypotheses.
      Overall, there is strong evidence that the Hp is involved in the specialization
      of spatial memory in scatter-hoarding animals. However, volume may be only a
      coarse proxy for more relevant and subtle changes in the structure of the brain
      underlying changes in behaviour. To better understand the nature of this
      brain/memory relationship, we suggest focusing on more specific and relevant
      features of the Hp, such as the number or size of neurons, variation in
      connectivity depending on dendritic and axonal arborization and the number of
      synapses. These should generate more specific hypotheses derived from a solid
      theoretical background and should provide a better understanding of both neural
      mechanisms of memory and their evolution.

PMID- 20156817
TI  - Seasonal hippocampal plasticity in food-storing birds.
AB  - Both food-storing behaviour and the hippocampus change annually in food-storing
      birds. Food storing increases substantially in autumn and winter in chickadees
      and tits, jays and nutcrackers and nuthatches. The total size of the chickadee
      hippocampus increases in autumn and winter as does the rate of hippocampal
      neurogenesis. The hippocampus is necessary for accurate cache retrieval in food
      storing birds and is much larger in food-storing birds than in non-storing
      passerines. It therefore seems probable that seasonal change in caching and
      seasonal change in the hippocampus are causally related. The peak in recruitment
      of new neurons into the hippocampus occurs before birds have completed food
      storing and cache retrieval for the year and may therefore be associated with
      spacing caches, encoding the spatial locations of caches, or creating a neuronal
      architecture involved in the recollection of cache sites. The factors controlling
      hippocampal plasticity in food-storing birds are not well understood.
      Photoperiodic manipulations that produce change in food-storing behaviour have no
      effect on either hippocampal size or neuronal recruitment. Available evidence
      suggests that changes in hippocampal size and neurogenesis may be a consequence
      of the behavioural and cognitive involvement of the hippocampus in storing and
      retrieving food.

PMID- 20156818
TI  - The ecological relevance of sleep: the trade-off between sleep, memory and energy
      conservation.
AB  - All animals in which sleep has been studied express signs of sleep-like
      behaviour, suggesting that sleep must have some fundamental functions that are
      sustained by natural selection. Those functions, however, are still not clear.
      Here, we examine the ecological relevance of sleep from the perspective of
      behavioural trade-offs that might affect fitness. Specifically, we highlight the
      advantage of using food-caching animals as a system in which a conflict might
      occur between engaging in sleep for memory/learning and hypothermia/torpor to
      conserve energy. We briefly review the evidence for the importance of sleep for
      memory, the importance of memory for food-caching animals and the conflicts that
      might occur between sleep and energy conservation in these animals. We suggest
      that the food-caching paradigm represents a naturalistic and experimentally
      practical system that provides the opportunity for a new direction in sleep
      research that will expand our understanding of sleep, especially within the
      context of ecological and evolutionary processes.

PMID- 20156820
TI  - Problems faced by food-caching corvids and the evolution of cognitive solutions.
AB  - The scatter hoarding of food, or caching, is a widespread and well-studied
      behaviour. Recent experiments with caching corvids have provided evidence for
      episodic-like memory, future planning and possibly mental attribution, all
      cognitive abilities that were thought to be unique to humans. In addition to the
      complexity of making flexible, informed decisions about caching and recovering,
      this behaviour is underpinned by a motivationally controlled compulsion to cache.
      In this review, we shall first discuss the compulsive side of caching both during
      ontogeny and in the caching behaviour of adult corvids. We then consider some of
      the problems that these birds face and review the evidence for the cognitive
      abilities they use to solve them. Thus, the emergence of episodic-like memory is
      viewed as a solution for coping with food perishability, while the various cache
      protection and pilfering strategies may be sophisticated tools to deprive
      competitors of information, either by reducing the quality of information they
      can gather, or invalidating the information they already have. Finally, we shall
      examine whether such future-oriented behaviour involves future planning and ask
      why this and other cognitive abilities might have evolved in corvids.

PMID- 20156821
TI  - How plants manipulate the scatter-hoarding behaviour of seed-dispersing animals.
AB  - Some plants that are dispersed by scatter-hoarding animals appear to have evolved
      the ability to manipulate the behaviour of those animals to increase the
      likelihood that seeds and nuts will be stored and that a portion of those items
      will not be recovered. Plants have achieved this in at least four ways. First, by
      producing large, nutritious seeds and nuts that are attractive to animals and
      that stimulate hoarding behaviour. Second, by imposing handling costs that cause
      animals to hoard rather than to eat items immediately. These handling costs can
      take one of two forms: physical barriers (e.g. hard seed coats) that take time to
      remove and secondary chemicals (e.g. tannins) that impose metabolic costs. Third,
      by masting, where a population of plants synchronizes reproductive effort,
      producing large nut crops at intervals of several years. Mast crops not only
      satiate seed predators, but also increase the amount of seed dispersal because
      scatter-hoarding animals are not easily satiated during caching (causing animals
      to store more food than they can consume) but are satiated during cache recovery.
      And fourth, by producing seeds that do not emit strong odours so that buried
      seeds are less likely to be discovered. These, and perhaps other, traits have
      increased the relative success of plant species with seeds dispersed by scatter
      hoarding animals.

PMID- 20156819
TI  - Physiological mechanisms for food-hoarding motivation in animals.
AB  - The study of ingestive behaviour has an extensive history, starting as early as
      1918 when Wallace Craig, an animal behaviourist, coined the terms 'appetitive'
      and 'consummatory' for the two-part sequence of eating, drinking and sexual
      behaviours. Since then, most ingestive behaviour research has focused on the
      neuroendocrine control of food ingestion (consummatory behaviour). The quantity
      of food eaten, however, is also influenced by the drive both to acquire and to
      store food (appetitive behaviour). For example, hamster species have a natural
      proclivity to hoard food and preferentially alter appetitive ingestive behaviours
      in response to environmental changes and/or metabolic hormones and neuropeptides,
      whereas other species would instead primarily increase their food intake.
      Therefore, with the strong appetitive component to their ingestive behaviour that
      is relatively separate from their consummatory behaviour, they seem an ideal
      model for elucidating the neuroendocrine mechanisms underlying the control of
      food hoarding and foraging. This review focuses on the appetitive side of
      ingestive behaviour, in particular food hoarding, attempting to integrate what is
      known about the neuroendocrine mechanisms regulating this relatively poorly
      studied behaviour. An hypothesis is formed stating that the direction of 'energy
      flux' is a unifying factor for the control of food hoarding.

PMID- 20156822
TI  - Metal clusters and nanoparticles.

PMID- 20156823
TI  - Determining the size-dependent structure of ligand-free gold-cluster ions.
AB  - Ligand-free metal clusters can be prepared over a wide size range, but only in
      comparatively small amounts. Determining their size-dependent properties has
      therefore required the development of experimental methods that allow
      characterization of sample sizes comprising only a few thousand mass-selected
      particles under well-defined collision-free conditions. In this review, we
      describe the application of these methods to the geometric structural
      determination of Au(n)(+) and Au(n)(-) with n = 3-20. Geometries were assigned by
      comparing experimental data, primarily from ion-mobility spectrometry and trapped
      ion electron diffraction, to structural models from quantum chemical
      calculations.

PMID- 20156824
TI  - Quantum chemical treatments of metal clusters.
AB  - This work focuses on finding and rationalizing the building principles of
      clusters with approximately 300 atoms of different types of metals: main group
      elements (Al, Sn), alkaline earth metals (Mg), transition metals (Pd) and
      clusters consisting of two different elements (Ir and Pt). Two tools are
      inevitable for this purpose: (i) quantum chemical methods that are able to treat
      a given cluster with both sufficient accuracy and efficiency and (ii) algorithms
      that are able to systematically scan the (3n-6)-dimensional potential surface of
      an n-atomic cluster for promising isomers. Currently, the only quantum chemical
      method that can be applied to metal clusters is density functional theory (DFT).
      Other methods either do not account for the multi-reference character of metal
      clusters or are too expensive and thus can be applied only to clusters of very
      few atoms, which usually is not sufficient for studying the building principles.
      The accuracy of DFT is not known a priori, but extrapolations to bulk values from
      calculated series of data show satisfying agreement with experimental data. For
      scans of the potential surface, simulated annealing techniques or genetic
      algorithms were used for the smaller clusters (approx. 20-30 atoms), and for the
      larger clusters considerations were restricted to selected packings and shapes.
      For the mixed-metallic clusters, perturbation theory turned out to be efficient
      and successful for finding the most promising distributions of the two atom types
      at the different sites.

PMID- 20156825
TI  - Polyhedral nine-atom clusters of tetrel elements and intermetalloid derivatives.
AB  - Homoatomic polyanions have the basic capability for a bottom-up synthesis of
      nanostructured materials. Therefore, the chemistry and the structures of
      polyhedral nine-atom clusters of tetrel elements [E(9)](4-) is highlighted. The
      nine-atom Zintl ions are available in good quantities for E = Si-Pb as binary
      alkali metal (A) phases of the composition A(4)E(9) or A(12)E(17). Dissolution or
      extraction of the neat solids with aprotic solvents and crystallization with
      alkali metal-sequestering molecules or crown ethers leads to a large variety of
      structures containing homoatomic clusters with up to 45 E atoms. Cluster growth
      occurs via oxidative coupling reactions. The clusters can further act as a donor
      ligand in transition metal complexes, which is a first step to the formation of
      bimetallic clusters. The structures and some nuclear magnetic resonance
      spectroscopic properties of these so-called intermetalloid clusters are reviewed,
      with special emphasis on tetrel clusters that are endohedrally filled with
      transition metal atoms.

PMID- 20156826
TI  - Metal clusters inside out.
AB  - Solid-state chemistry of cluster compounds with metals in the left part of the
      periodic table is described. As a function of the metal valence electron
      concentration (VEC), characteristic changes occur with stepwise changing
      features. Strongly metal-metal-bonded and ligand-encapsulated clusters exist for
      large values of VEC. At decreased values, endohedral atoms stabilize the
      clusters, and with the lowest values, only clusters exist with no ligand shell.
      This general trend holds for systems with discrete, as well as condensed,
      clusters as illustrated for d metals, including the lanthanides, alkaline earth
      and alkali metals.

PMID- 20156827
TI  - Syntheses, structures and properties of primarily nanosized homo/heterometallic
      palladium CO/PR3-ligated clusters.
AB  - Syntheses, properties and structures of nanosized palladium CO/PR(3)-ligated homo
      and heterometallic clusters containing up to 165 metal atoms are the focus of
      this review. The work discussed is primarily that of the authors and their
      coworkers. We propose that the unparalleled variety of structural types and the
      distinctive reactivities of neutral Pd(n)(CO)(x)(PR(3))(y) clusters composed of
      zerovalent Pd atoms are a consequence of relatively weak Pd-L(ligand) and Pd(0)
      Pd(0) interactions that result from the stable 5s(0)4d(10) closed-shell electron
      configuration of atomic Pd in its ground state.

PMID- 20156828
TI  - Surface modification, functionalization and bioconjugation of colloidal inorganic
      nanoparticles.
AB  - Inorganic colloidal nanoparticles are very small, nanoscale objects with
      inorganic cores that are dispersed in a solvent. Depending on the material they
      consist of, nanoparticles can possess a number of different properties such as
      high electron density and strong optical absorption (e.g. metal particles, in
      particular Au), photoluminescence in the form of fluorescence (semiconductor
      quantum dots, e.g. CdSe or CdTe) or phosphorescence (doped oxide materials, e.g.
      Y(2)O(3)), or magnetic moment (e.g. iron oxide or cobalt nanoparticles).
      Prerequisite for every possible application is the proper surface
      functionalization of such nanoparticles, which determines their interaction with
      the environment. These interactions ultimately affect the colloidal stability of
      the particles, and may yield to a controlled assembly or to the delivery of
      nanoparticles to a target, e.g. by appropriate functional molecules on the
      particle surface. This work aims to review different strategies of surface
      modification and functionalization of inorganic colloidal nanoparticles with a
      special focus on the material systems gold and semiconductor nanoparticles, such
      as CdSe/ZnS. However, the discussed strategies are often of general nature and
      apply in the same way to nanoparticles of other materials.

PMID- 20156829
TI  - Synthesis of noble metal nanoparticles and their non-ordered superstructures.
AB  - This article highlights our recent work concerning the synthesis of metal
      nanoparticles and their non-ordered superstructures. After a short introduction,
      the basic synthetic procedures are explained for the nanoparticles used for the
      assemblies. Furthermore, a fabrication method is itemized for very monodisperse
      platinum nanoparticles in aqueous solution ranging in diameter from 10 to 100 nm
      showing distinct optical properties. The next section deals with the synthesis of
      non-ordered hydro- and aerogels from the as-prepared sols. Very light large
      surface materials from gold, silver, platinum and gold-silver and platinum-silver
      sols can be fabricated with the given method. Another way to ultralight
      superstructures of noble metal nanoparticles using fungi as templates is
      described in the third section. Although fungi grow inside the colloidal
      solutions they can assemble the nanoparticles onto their surfaces. These hybrid
      systems are thus extremely interesting supported superstructures for applications
      in heterogeneous catalysis, since the numbers of nanoparticles on the fungus can
      easily be tuned, and the fabrication process is cost-effective, environmentally
      friendly and the organic templates can be easily removed by simple combustion for
      regaining the noble metal.

PMID- 20156830
TI  - On the application potential of gold nanoparticles in nanoelectronics and
      biomedicine.
AB  - Ligand-stabilized gold nanoparticles (AuNPs) are of high interest to research
      dedicated to future technologies such as nanoelectronics or biomedical
      applications. This research interest arises from the unique size-dependent
      properties such as surface plasmon resonance or Coulomb charging effects. It is
      shown here how the unique properties of individual AuNPs and AuNP assemblies can
      be used to create new functional materials for applications in a technical or
      biological environment. While the term technical environment focuses on the
      potential use of AuNPs as subunits in nanoelectronic devices, the term biological
      environment addresses issues of toxicity and novel concepts of controlling
      biomolecular reactions on the surface of AuNPs.

PMID- 20156831
TI  - Metal chalcogenide nanoclusters with 'tailored' surfaces via 'designer' silylated
      chalcogen reagents.
AB  - Silylated chalcogen reagents are proven entry points for the preparation of
      ligand-stabilized, nanometre-sized metal-chalcogen clusters. More recently, these
      reagents have been developed to incorporate specific functionalities onto the
      surfaces of nanoclusters. The group 11 metals Cu and Ag in particular yield a
      wealth of structural types, the features for which are dependent on the nature of
      the surface chalcogenolate ligands. The content of this review focuses on
      complexes that have been structurally characterized by single-crystal X-ray
      diffraction studies and illustrates the ease by which these frameworks can be
      assembled.

PMID- 20156832
TI  - Ruthenium-tin cluster complexes and their applications as bimetallic nanoscale
      heterogeneous hydrogenation catalysts.
AB  - This review describes recent studies on the synthesis and characterization of new
      polynuclear ruthenium-tin cluster complexes, their conversion to heterometallic
      nanoparticles, and some studies on their applications as catalysts for the
      hydrogenation of unsaturated organic molecules of commercial interest.

PMID- 20156833
TI  - Synthesis and catalytic activity of metal nanoclusters inside functional resins:
      an endeavour lasting 15 years.
AB  - Cross-linked functional polymers (functional resins) are versatile, designable
      and useful supports for metal nanoclusters that are able to provide reasonably
      thermally and mechanically stable multi-functional metal catalysts characterized
      by good activity and selectivity. The paper reviews authors' contributions to the
      field from the early 1990s to the present.

PMID- 20156834
TI  - Magnetic coordination clusters and networks: synthesis and topological
      description.
AB  - With the discovery of the phenomenon of single-molecule magnetism, coordination
      chemists have turned their attention to synthesizing cluster aggregates of
      paramagnetic ions. This has led to a plethora of coordination clusters with
      various topologies and diverse magnetic properties. In this paper, we present
      ways of describing and understanding such compounds as well as outlining a new
      approach, which we have recently developed, to describing cluster topology. Our
      approach is based upon and pays tribute to the huge contribution made to
      coordination chemistry through the development of the Schlafli symbols for
      describing architectures. To illustrate the developments that are taking place in
      modern coordination chemistry, we start with some basic definitions of relevance
      to what follows. Then we describe approaches to discovering new magnetically
      interesting 3d/4f clusters, assigning their topological descriptions. Finally, we
      show how the concepts behind the construction of metal-organic frameworks can be
      extended to using clusters as nodes in the frameworks to give super metal-organic
      frameworks.

PMID- 20156835
TI  - Oxidised regenerated cellulose: an unusual cause of paraplegia following
      oesophagectomy.
AB  - Oesophageal resection after neoadjuvant therapy is the treatment of choice in
      localized oesophageal cancer. Common complications after oesophagectomy include
      pulmonary infection and anastomotic leaks. Paraplegia or paraparesis after
      oesophagectomy is an extremely uncommon occurrence and has not been reported in
      medical literature. Possible causes include injury to the spinal cord due to
      epidural catheter insertion, epidural haematoma and anterior spinal artery
      thrombosis. Pressure on the spinal cord due to migrated oxidised regenerated
      cellulose (ORC) is an extremely rare cause. Meticulous haemostasis at the
      costovertebral angle with a combination of pressure and electrocautery is
      advocated to prevent this rare but catastrophic complication. We describe a
      middle aged woman who developed post-thoracotomy paraplegia following ORC
      compression on the spinal cord.

PMID- 20156836
TI  - Involvement of mitochondria-mediated apoptosis in ethylbenzene-induced renal
      toxicity in rat.
AB  - Ethylbenzene is an important industrial chemical that has recently been
      classified as a possible human carcinogen (International Agency of Research on
      Cancer class 2B), but the available data do not support the genotoxic mechanism
      of ethylbenzene-induced tumors in kidney. We investigated the effects of
      ethylbenzene on renal ultrastructure and explored the nongenotoxic mechanism of
      mitochondria-mediated apoptosis pathway. Forty male Sprague-Dawley rats were used
      as a vivo model with ethylbenzene inhalation for 13 weeks, and the metabolites of
      ethylbenzene, mandelic acid (MA), and phenylglyoxylic acid (PGA) in urine were
      examined by high-performance liquid chromatography. Meanwhile, the ultrastructure
      of renal tubular epithelial cells was observed, and cell apoptosis was detected
      via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.
      Furthermore, we investigated the expression levels of messenger RNA (mRNA) and
      protein of bax, bcl-2, cytochrome c, caspase-9, and caspase-3 in rat kidney. With
      respect to levels of MA, PGA, and MA + PGA, a significant dose-dependent increase
      was observed in 4335 and 6500 mg/m(3) ethylbenzene-treated groups against the
      control group. The mitochondria of renal tubular epithelial cells became a
      compact and vacuolar structure in 6500 mg/m(3) ethylbenzene-treated group, and
      ethylbenzene induced a significant increase in the number of apoptotic cells as
      compared to the control group. In addition, enhanced mRNA and protein expression
      levels of all measured genes were observed in various ethylbenzene-treated groups
      except the decreased bcl-2 expression levels. Our results indicated that
      ethylbenzene may induce apoptosis of renal tubular epithelial cells via
      mitochondria-mediated apoptotic pathways. MA and PGA in urine might be a
      parameter of biological dose in vivo after ethylbenzene inhalation.

PMID- 20156837
TI  - Lack of significant dermal penetration of titanium dioxide from sunscreen
      formulations containing nano- and submicron-size TiO2 particles.
AB  - Titanium dioxide (TiO(2)) is included in some sunscreen formulations to
      physically block ultraviolet radiation. A dermal penetration study was conducted
      in minipigs with three TiO(2) particles (uncoated submicron sized, uncoated nano
      sized, and dimethicone/methicone copolymer-coated nanosized) applied 5% by weight
      in a sunscreen. These and control formulations were topically applied to minipigs
      at 2 mg cream/cm(2) skin (4 applications/day, 5 days/week, 4 weeks). Skin
      (multiple sites), lymph nodes, liver, spleen, and kidneys were removed, and the
      TiO(2) content was determined (as titanium) using inductively coupled plasma mass
      spectroscopy. Titanium levels in lymph nodes and liver from treated animals were
      not increased over the values in control animals. The epidermis from minipigs
      treated with sunscreens containing TiO(2) showed elevated titanium. Increased
      titanium was detected in abdominal and neck dermis of minipigs treated with
      uncoated and coated nanoscale TiO(2). Using electron microscopy-energy dispersive
      x-ray analysis, all three types of TiO(2) particles were found in the stratum
      corneum and upper follicular lumens in all treated skin samples (more particles
      visible with coated nanoscale TiO(2)). Isolated titanium particles were also
      present at various locations in the dermis of animals treated with all three
      types of TiO(2)-containing sunscreens; however, there was no pattern of
      distribution or pathology suggesting the particles could be the result of
      contamination. At most, the few isolated particles represent a tiny fraction of
      the total amount of applied TiO(2). These findings indicate that there is no
      significant penetration of TiO(2) nanoparticles through the intact normal
      epidermis.

PMID- 20156838
TI  - Atypical subunit composition of the chlorophycean mitochondrial F1FO-ATP synthase
      and role of Asa7 protein in stability and oligomycin resistance of the enzyme.
AB  - In yeast, mammals, and land plants, mitochondrial F(1)F(O)-ATP synthase (complex
      V) is a remarkable enzymatic machinery that comprises about 15 conserved
      subunits. Peculiar among eukaryotes, complex V from Chlamydomonadales algae
      (order of chlorophycean class) has an atypical subunit composition of its
      peripheral stator and dimerization module, with nine subunits of unknown
      evolutionary origin (Asa subunits). In vitro, this enzyme exhibits an increased
      stability of its dimeric form, and in vivo, Chlamydomonas reinhardtii cells are
      insensitive to oligomycins, which are potent inhibitors of proton translocation
      through the F(O) moiety. In this work, we showed that the atypical features of
      the Chlamydomonadales complex V enzyme are shared by the other chlorophycean
      orders. By biochemical and in silico analyses, we detected several atypical Asa
      subunits in Scenedesmus obliquus (Sphaeropleales) and Chlorococcum ellipsoideum
      (Chlorococcales). In contrast, complex V has a canonical subunit composition in
      other classes of Chlorophytes (Trebouxiophyceae, Prasinophyceae, and Ulvophyceae)
      as well as in Streptophytes (land plants), and in Rhodophytes (red algae).
      Growth, respiration, and ATP levels in Chlorophyceae were also barely affected by
      oligomycin concentrations that affect representatives of the other classes of
      Chlorophytes. We finally studied the function of the Asa7 atypical subunit by
      using RNA interference in C. reinhardtii. Although the loss of Asa7 subunit has
      no impact on cell bioenergetics or mitochondrial structures, it destabilizes in
      vitro the enzyme dimeric form and renders growth, respiration, and ATP level
      sensitive to oligomycins. Altogether, our results suggest that the loss of
      canonical components of the complex V stator happened at the root of
      chlorophycean lineage and was accompanied by the recruitment of novel
      polypeptides. Such a massive modification of complex V stator features might have
      conferred novel properties, including the stabilization of the enzyme dimeric
      form and the shielding of the proton channel. In these respects, we discuss an
      evolutionary scenario for F(1)F(O)-ATP synthase in the whole green lineage (i.e.,
      Chlorophyta and Streptophyta).

PMID- 20156839
TI  - Dissemination of effective physical activity interventions: are we applying the
      evidence?
AB  - BACKGROUND: Given sparse knowledge on dissemination, this study sought to explore
      key benefits, barriers and contextual factors that are perceived to be important
      to the adoption and implementation of the 'Community Guide's' evidence-based
      physical activity recommendations. DESIGN: We conducted case studies in two
      states where extensive adoption and implementation of the Guide's recommendations
      have occurred and in two states where widespread dissemination has lagged.
      Interviews (n = 76) were semi-structured and included both quantitative and
      qualitative methods. Participant perceptions from the following areas were
      examined: (i) priority of physical activity, (ii) awareness of and ability to
      define the term 'evidence-based approaches' and (iii) awareness, adoption,
      facilitators, benefits, challenges and barriers to Guide adoption. RESULTS: Key
      enabling factors among high capacity states included: funds and direction from
      the Centers for Disease Control and Prevention; leadership support; capable
      staff; and successful partnerships and collaborations. Restraining forces among
      low capacity states included: the Guide recommendations being too new;
      participants being too new to current job; lack of time and training on how to
      use the Guide recommendations; limited funds and other resources and lack of
      leadership. CONCLUSION: To be effective, we must gain an understanding of
      contextual factors when designing for dissemination.

PMID- 20156840
TI  - Perisomatic GABAergic innervation in prefrontal cortex is regulated by ankyrin
      interaction with the L1 cell adhesion molecule.
AB  - The L1 adhesion molecule functions in axon growth and guidance, but a role in
      synaptic development of cortical inhibitory interneurons is largely unexplored.
      L1 mediates adhesion by engaging the actin cytoskeleton through binding the
      actin/spectrin adapter protein ankyrin. Loss of L1-ankyrin interaction impaired
      process elaboration/branching by GABAergic interneurons, including basket cells,
      and reduced the number of perisomatic synapses in the cingulate cortex as shown
      in L1 mutant mice (L1YH) with a mutation in the ankyrin-binding site, either
      alone or intercrossed with GAD67-enhanced green fluorescence protein reporter
      mice. Electron microscopy revealed that perisomatic inhibitory synapses but not
      excitatory synapses in the neuropil were specifically affected. In wild-type
      cingulate cortex, L1 colocalized with perisomatic synaptic markers, whereas L1
      phosphorylation on Tyr(1229) decreased postnatally, correlating with increased
      ankyrin binding and synaptic development. These results suggest a novel role for
      L1 engagement with the actin cytoskeleton in development of inhibitory
      connectivity within the cingulate cortex.

PMID- 20156842
TI  - Control of starch branching in barley defined through differential RNAi
      suppression of starch branching enzyme IIa and IIb.
AB  - The roles of starch branching enzyme (SBE, EC 2.4.1.18) IIa and SBE IIb in
      defining the structure of amylose and amylopectin in barley (Hordeum vulgare)
      endosperm were examined. Barley lines with low expression of SBE IIa or SBE IIb,
      and with the low expression of both isoforms were generated through RNA-mediated
      silencing technology. These lines enabled the study of the role of each of these
      isoforms in determining the amylose content, the distribution of chain lengths,
      and the frequency of branching in both amylose and amylopectin. In lines where
      both SBE IIa and SBE IIb expression were reduced by >80%, a high amylose
      phenotype (>70%) was observed, while a reduction in the expression of either of
      these isoforms alone had minor impact on amylose content. The structure and
      properties of the high amylose starch resulting from the concomitant reduction in
      the expression of both isoforms of SBE II in barley were found to approximate
      changes seen in amylose extender mutants of maize, which result from lesions
      eliminating expression of the SBE IIb gene. Amylopectin chain length distribution
      analysis indicated that both SBE IIa and SBE IIb isoforms play distinct roles in
      determining the fine structure of amylopectin. A significant reduction in the
      frequency of branches in amylopectin was noticed only when both SBE IIa and SBE
      IIb were reduced, whereas there was a significant increase in the branching
      frequency of amylose when SBE IIb alone was reduced. Functional interactions
      between SBE isoforms are suggested, and a possible inhibitory role of SBE IIb on
      other SBE isoforms is discussed.

PMID- 20156841
TI  - Specialization of the rostral prefrontal cortex for distinct analogy processes.
AB  - Analogical reasoning is central to learning and abstract thinking. It involves
      using a more familiar situation (source) to make inferences about a less familiar
      situation (target). According to the predominant cognitive models, analogical
      reasoning includes 1) generation of structured mental representations and 2)
      mapping based on structural similarities between them. This study used functional
      magnetic resonance imaging to specify the role of rostral prefrontal cortex (PFC)
      in these distinct processes. An experimental paradigm was designed that enabled
      differentiation between these processes, by temporal separation of the
      presentation of the source and the target. Within rostral PFC, a lateral
      subregion was activated by analogy task both during study of the source (before
      the source could be compared with a target) and when the target appeared. This
      may suggest that this subregion supports fundamental analogy processes such as
      generating structured representations of stimuli but is not specific to one
      particular processing stage. By contrast, a dorsomedial subregion of rostral PFC
      showed an interaction between task (analogy vs. control) and period (more
      activated when the target appeared). We propose that this region is involved in
      comparison or mapping processes. These results add to the growing evidence for
      functional differentiation between rostral PFC subregions.

PMID- 20156843
TI  - The impact of quercetin on cisplatin-induced clastogenesis and apoptosis in
      murine marrow cells.
AB  - The aim of the present investigation is to determine whether the quercetin in
      combination with cisplatin can ameliorate cisplatin-induced clastogenesis and
      apoptosis in the bone marrow cells of mice. The scoring of chromosomal
      aberrations, micronuclei and mitotic activity were undertaken in the current
      study as markers of clastogenicity. Apoptosis was analysed by the Annexin V
      propidium iodide assay and the occurrence of a hypodiploid DNA peak. Oxidative
      stress markers such as bone marrow lipid peroxidation and reduced glutathione
      were assessed as a possible mechanism underlying this amelioration. Quercetin was
      neither clastogenic nor apoptogenic in mice at doses equivalent to 50 or 100
      mg/kg for 2 days. Pre-treatment of mice with quercetin significantly reduced
      cisplatin-induced clastogenesis and apoptosis in the bone marrow cells and these
      effects were dose and time dependent. Prior administration of quercetin ahead of
      cisplatin challenge ameliorated oxidative stress markers. Overall, this study
      provides for the first time that quercetin has a protective role in the abatement
      of cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice
      that resides, at least in part, in its antioxidant effects. Therefore, quercetin
      can be a good candidate to decrease the deleterious effects of cisplatin in the
      bone marrow cells of cancer patients treated with this drug.

PMID- 20156844
TI  - Mixed GABA-glycine synapses delineate a specific topography in the nucleus
      tractus solitarii of adult rat.
AB  - Using combined morphological and electrophysiological approaches, we have
      determined the composition of inhibitory synapses of the nucleus tractus
      solitarii (NTS), a brainstem structure that is a gateway for many visceral
      sensory afferent fibres. Immunohistochemical experiments demonstrate that, in
      adult rat, GABA axon terminals are present throughout the NTS while mixed GABA
      glycine axon terminals are strictly located to the lateral part of the NTS within
      subnuclei surrounding the tractus solitarius. Purely glycine axon terminals are
      rare in the lateral part of the NTS and hardly detected in its medial part.
      Electrophysiological experiments confirm the predominance of GABA inhibition
      throughout the NTS and demonstrate the existence of a dual inhibition involving
      the co-release of GABA and glycine restricted to the lateral part of NTS. Since
      GABA(A) and glycine receptors are co-expressed postsynaptically in virtually all
      the inhibitory axon terminals throughout the NTS, it suggests that the inhibition
      phenotype relies on the characteristics of the axon terminals. Our results also
      demonstrate that glycine is mostly associated with GABA within axon terminals and
      raise the possibility of a dynamic regulation of GABA/glycine release at the
      presynaptic level. Our data provide new information for understanding the
      mechanisms involved in the processing of visceral information by the central
      nervous system in adult animals.

PMID- 20156845
TI  - Cystic fibrosis transmembrane conductance regulator trafficking modulates the
      barrier function of airway epithelial cell monolayers.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is an integral
      membrane glycoprotein which functions as an anion channel and influences diverse
      cellular processes. We studied its role in the development of epithelial
      tightness by expressing wild-type (WT-CFTR) or mutant (Delta F508-CFTR) CFTR in
      human airway epithelial cell monolayers cultured at the air-liquid interface.
      Green fluorescent protein (GFP)-tagged WT or Delta F508 constructs were expressed
      in the CF bronchial cell line CFBE41o(-) using adenoviruses, and the results were
      compared with those obtained using CFBE41o(-) lines stably complemented with wild
      type or mutant CFTR. As predicted, GFP-Delta WT-CFTR reached the apical membrane
      whereas GFP-F508-CFTR was only detected intracellularly. Although CFTR expression
      would be expected to reduce transepithelial resistance (TER), expressing GFP-CFTR
      significantly increased the TER of CFBE41o(-) monolayers whilst GFP-Delta F508
      CFTR had no effect. Similar results were obtained with cell lines stably
      overexpressing Delta F508-CFTR or WT-CFTR. Preincubating Delta F508-CFTR
      monolayers at 29 degrees C reduced mannitol permeability and restored TER, and
      the effect on TER was reversible during temperature oscillations. Expression of
      GFP-Delta F508-CFTR or GFP-WT-CFTR in a cell line already containing endogenous
      WT-CFTR (Calu-3) did not alter TER. The CFTR- and temperature-dependence of TER
      were not affected by the CFTR inhibitor CFTR(inh)172 or low-chloride medium;
      therefore the effect of CFTR on barrier function was unrelated to its ion channel
      activity. Modulation of TER was blunted but not eliminated by genistein, implying
      the involvement of tyrosine phosphorylation and other mechanisms. Modulation of
      CFTR trafficking was correlated with an increase in tight junction depth. The
      results suggest that CFTR trafficking is required for the normal organisation and
      function of tight junctions. A reduction in barrier function caused by
      endoplasmic reticulum retention of Delta F508-CFTR may contribute to fluid
      hyperabsorption in CF airways.

PMID- 20156846
TI  - Human vagal baroreflex mechanisms in space.
AB  - Although astronauts' cardiovascular function is normal while they are in space,
      many have altered haemodynamic responses to standing after they return to Earth,
      including inordinate tachycardia, orthostatic hypotension, and uncommonly,
      syncope. Simulated microgravity impairs vagal baroreceptor-cardiac reflex
      function and causes orthostatic hypotension. Actual microgravity, however, has
      been shown to either increase, or not change vagal baroreflex gain. In this
      study, we tested the null hypothesis that spaceflight does not impair human
      baroreflex mechanisms. We studied 11 American and two German astronauts before,
      during (flight days 2-8), and after two, 9- and 10-day space shuttle missions,
      with graded neck pressure and suction, to elicit sigmoid, vagally mediated
      carotid baroreflex R-R interval responses. Baseline systolic pressures tended to
      be higher in space than on Earth (P = 0.015, repeated measures analysis of
      variance), and baseline R-R intervals tended to be lower (P = 0.049).
      Baroreceptor-cardiac reflex relations were displaced downward on the R-R interval
      axis in space. The average range of R-R interval responses to neck pressure
      changes declined from preflight levels by 37% on flight day 8 (P = 0.051),
      maximum R-R intervals declined by 14% (P = 0.003), and vagal baroreflex gain by
      9% (P = 0.009). These measures returned to preflight levels by 7-10 days after
      astronauts returned to Earth. This study documents significant increases of
      arterial pressure and impairment of vagal baroreflex function in space. These
      results and results published earlier indicate that microgravity exposure
      augments sympathetic, and diminishes vagal cardiovascular influences.

PMID- 20156847
TI  - Voltage-sensor mutations in channelopathies of skeletal muscle.
AB  - Mutations of voltage-gated ion channels cause several channelopathies of skeletal
      muscle, which present clinically with myotonia, periodic paralysis, or a
      combination of both. Expression studies have revealed both loss-of-function and
      gain-of-function defects for the currents passed by mutant channels. In many
      cases, these functional changes could be mechanistically linked to the defects of
      fibre excitability underlying myotonia or periodic paralysis. One remaining
      enigma was the basis for depolarization-induced weakness in hypokalaemic periodic
      paralysis (HypoPP) arising from mutations in either sodium or calcium channels.
      Curiously, 14 of 15 HypoPP mutations are at arginines in S4 voltage sensors, and
      recent observations show that these substitutions support an alternative pathway
      for ion conduction, the gating pore, that may be the source of the aberrant
      depolarization during an attack of paralysis.

PMID- 20156848
TI  - Genetic and functional characterisation of the P/Q calcium channel in episodic
      ataxia with epilepsy.
AB  - Mutations in CACNA1A, which encodes the principal subunit of the P/Q calcium
      channel, underlie episodic ataxia type 2 (EA2). In addition, some patients with
      episodic ataxia complicated by epilepsy have been shown to harbour CACNA1A
      mutations, raising the possibility that P/Q channel dysfunction may be linked to
      human epilepsy. We undertook a review of all published CACNA1A EA2 cases and this
      showed that 7% have epilepsy--representing a sevenfold increased epilepsy risk
      compared to the background population risk (P<0.001). We also studied a series of
      17 individuals with episodic ataxia accompanied by epilepsy and/or clearly
      epileptiform electroencephalograms (EEGs). We screened the entire coding region
      of CACNA1A for point mutations and rearrangements to determine if genetic
      variation in the gene is associated with the epilepsy phenotype, and measured the
      functional impact of all missense variations on heterologously expressed P/Q
      channels. We identified two large scale deletions and two new missense mutations
      in CACNA1A. When expressed, L621R had little detectable effect on P/Q channel
      function, while the other missense change, G540R, caused an approximately 30%
      reduction in current density. In nine patients we also identified the previously
      reported non-synonymous coding variants (E921D and E993V) which also resulted in
      impairment of P/Q channel function. Taken together, 12 of the 17 patients have
      genetic changes which decrease P/Q channel function. We conclude that variants in
      the coding region of CACNA1A that confer a loss of P/Q-type channel function are
      associated with episodic ataxia and epilepsy. Our data suggest that functional
      stratification of all variants, including common polymorphisms, rare variants and
      novel mutations, may provide new insights into the mechanisms of channelopathies.

PMID- 20156849
TI  - Effects of substitution of Cx43 by Cx32 on myocardial energy metabolism,
      tolerance to ischaemia and preconditioning protection.
AB  - Connexin 43 (Cx43) plays an important role in cardioprotective signalling by
      mechanisms at least in part independent of gap junctional communication. To
      investigate whether this role is related to specific properties of this connexin
      isoform, we used a knock-in mouse model in which the coding region of Cx43 is
      replaced by that of Cx32. Homozygous Cx43KI32 mice showed reduced cell-to-cell
      Lucifer Yellow transfer (P < 0.01), but QRS duration and left ventricular
      fractional shortening (echocardiography) were similar to those in wild-type
      animals. NMR spectroscopy detected reduced ATP and increased lactate content in
      myocardium from homozygous Cx43KI32 animals (P < 0.05). Despite this, isolated
      homozygous Cx43KI32 hearts showed smaller infarcts after ischaemia-reperfusion
      (40 min/60 min) as compared to hearts from heterozygous and wild-type animals (13
      and 31% reduction, respectively, P < 0.05). Cardiac myocytes isolated from
      Cx43KI32 mouse hearts also showed a reduced rate of cell death after simulated
      ischaemia-reperfusion. In a separate series of experiments, both ischaemic (4
      cycles of 3.5 min of ischaemia and 5 min of reperfusion) and pharmacological (50
      micromol l(-1) diazoxide, 10 min) preconditioning reduced infarct size in hearts
      from wild-type mice (by 24.84 and 26.63%, respectively, P < 0.05), but only
      ischaemic preconditioning was effective in hearts from heterozygous animals and
      both preconditioning strategies failed to protect Cx43KI32 homozygous hearts.
      These results demonstrate that Cx43 has an important and previously unknown
      modulatory effect in myocardial energy metabolism and tolerance to ischaemia, and
      plays a critical role in preconditioning protection, by mechanisms that are
      specific for this connexin isoform.

PMID- 20156850
TI  - Histamine H3 receptor activation decreases kainate-induced hippocampal gamma
      oscillations in vitro by action potential desynchronization in pyramidal neurons.
AB  - The study of rhythmic electrical activity in slice preparations has generated
      important insights into neural network function. While the synaptic mechanisms
      involved in the generation of in vitro network oscillations have been studied
      widely, little is known about the modulatory influence exerted on rhythmic
      activity in neuronal networks by neuropeptides and biogenic amines. Gamma
      oscillations play an important role in cognitive processes and are altered or
      disrupted in disorders such as Alzheimer's disease (AD) and schizophrenia. Given
      the importance of gamma oscillations for learning, memory and cognition processes
      as well as the recent interest in histamine H(3) receptors in the development of
      pro-cognitive drugs to treat disorders such as AD and schizophrenia, it is
      relevant to study the impact of histaminergic mechanisms on network gamma
      oscillations. Here we show for the first time a modulation of gamma oscillation
      by histaminergic mechanisms. Selective activation of the H(3) receptor by R-alpha
      methylhistamine significantly reduces the power of kainate-induced gamma
      oscillations, but not carbachol-induced gamma oscillations, in the rat
      hippocampal slice preparation without affecting oscillation frequency. This
      effect is neither caused by a decrease in excitatory or inhibitory postsynaptic
      currents, nor a decrease in cellular excitability. Instead, we find that the
      decrease in oscillation power following H(3) receptor activation results from a
      desynchronization of pyramidal neuron action potential firing with regard to the
      local field potential oscillation cycle. Our data provide a possible mechanism of
      action for histamine in regulating gamma oscillations in the hippocampal network.

PMID- 20156851
TI  - Rapid time course of action potentials in spines and remote dendrites of mouse
      visual cortex neurons.
AB  - Axonally initiated action potentials back-propagate into spiny dendrites of
      central mammalian neurons and thereby regulate plasticity at excitatory synapses
      on individual spines as well as linear and supralinear integration of synaptic
      inputs along dendritic branches. Thus, the electrical behaviour of individual
      dendritic spines and terminal dendritic branches is critical for the integrative
      function of nerve cells. The actual dynamics of action potentials in spines and
      terminal branches, however, are not entirely clear, mostly because electrode
      recording from such small structures is not feasible. Additionally, the available
      membrane potential imaging techniques are limited in their sensitivity and
      require substantial signal averaging for the detection of electrical events at
      the spatial scale of individual spines. We made a critical improvement in the
      voltage-sensitive dye imaging technique to achieve multisite recordings of
      backpropagating action potentials from individual dendritic spines at a high
      frame rate. With this approach, we obtained direct evidence that in layer 5
      pyramidal neurons from the visual cortex of juvenile mice, the rapid time course
      of somatic action potentials is preserved throughout all cellular compartments,
      including dendritic spines and terminal branches of basal and apical dendrites.
      The rapid time course of the action potential in spines may be a critical
      determinant for the precise regulation of spike timing-dependent synaptic
      plasticity within a narrow time window.

PMID- 20156853
TI  - Who regulates the regulators?

PMID- 20156852
TI  - How do schizophrenia patients use visual information to decode facial emotion?
AB  - Impairment in recognizing facial emotions is a prominent feature of schizophrenia
      patients, but the underlying mechanism of this impairment remains unclear. This
      study investigated the specific aspects of visual information that are critical
      for schizophrenia patients to recognize emotional expression. Using the Bubbles
      technique, we probed the use of visual information during a facial emotion
      discrimination task (fear vs. happy) in 21 schizophrenia patients and 17 healthy
      controls. Visual information was sampled through randomly located Gaussian
      apertures (or "bubbles") at 5 spatial frequency scales. Online calibration of the
      amount of face exposed through bubbles was used to ensure 75% overall accuracy
      for each subject. Least-square multiple linear regression analyses between
      sampled information and accuracy were performed to identify critical visual
      information that was used to identify emotional expression. To accurately
      identify emotional expression, schizophrenia patients required more exposure of
      facial areas (i.e., more bubbles) compared with healthy controls. To identify
      fearful faces, schizophrenia patients relied less on bilateral eye regions at
      high-spatial frequency compared with healthy controls. For identification of
      happy faces, schizophrenia patients relied on the mouth and eye regions; healthy
      controls did not utilize eyes and used the mouth much less than patients did.
      Schizophrenia patients needed more facial information to recognize emotional
      expression of faces. In addition, patients differed from controls in their use of
      high-spatial frequency information from eye regions to identify fearful faces.
      This study provides direct evidence that schizophrenia patients employ an
      atypical strategy of using visual information to recognize emotional faces.

PMID- 20156854
TI  - Will my child live?

PMID- 20156855
TI  - Emergency department triage revisited.
AB  - Triage is a process that is critical to the effective management of modern
      emergency departments. Triage systems aim, not only to ensure clinical justice
      for the patient, but also to provide an effective tool for departmental
      organisation, monitoring and evaluation. Over the last 20 years, triage systems
      have been standardised in a number of countries and efforts made to ensure
      consistency of application. However, the ongoing crowding of emergency
      departments resulting from access block and increased demand has led to calls for
      a review of systems of triage. In addition, international variance in triage
      systems limits the capacity for benchmarking. The aim of this paper is to provide
      a critical review of the literature pertaining to emergency department triage in
      order to inform the direction for future research. While education, guidelines
      and algorithms have been shown to reduce triage variation, there remains
      significant inconsistency in triage assessment arising from the diversity of
      factors determining the urgency of any individual patient. It is timely to accept
      this diversity, what is agreed, and what may be agreeable. It is time to develop
      and test an International Triage Scale (ITS) which is supported by an
      international collaborative approach towards a triage research agenda. This
      agenda would seek to further develop application and moderating tools and to
      utilise the scales for international benchmarking and research programmes.

PMID- 20156857
TI  - Risk of suicide and fatal drug poisoning after discharge from the emergency
      department: a nested case-control study.
AB  - OBJECTIVES: The objectives were to study the risk of suicide and fatal drug
      poisoning among emergency department users who had been discharged home, based on
      the main diagnoses selected by the emergency physician upon discharge. METHODS:
      This is a case-control study nested in a cohort of users of the emergency
      department who had been discharged. The cases of suicide (n=41) and fatal drug
      poisoning (n=21) were identified from the National Cause-of-death Registry, and
      five times as many controls were selected from users of the emergency department.
      Multivariate logistic regression analysis was used to calculate the OR and 95% CI
      adjusted for age and gender. RESULTS: Frequent visits to the emergency department
      were significantly associated with suicide and fatal poisoning. The study period
      spanned 7 years. The OR for suicide among cases and controls was 7.84 for those
      diagnosed as having mental disorders, 96.89 for those with use of alcohol, 24.51
      for those with drug intoxication and 2.69 for those with a non-causative
      diagnosis. The OR for fatal poisoning for cases and controls was 12.26 for those
      with use of alcohol, 37.22 for those with drug intoxication and 5.76 for those
      with the classification category factors influencing health status. CONCLUSIONS:
      The clinical implication is that patients with any combination of previous main
      diagnoses of mental disorder, alcohol use, drug intoxication, a non-causative
      diagnosis or with the classification category factors influencing health status
      should be evaluated and assessed for potential risk of suicide or fatal drug
      poisoning.

PMID- 20156858
TI  - Reduced productivity among junior trainees in the emergency department and the
      impact on senior clinicians.
AB  - Emergency medicine has recently undergone significant changes, with training,
      staffing and service delivery attracting particular attention. Senior doctors are
      under increased pressure to ensure the prompt delivery of service and to provide
      a smooth patient journey. It has been suggested that junior trainees see fewer
      patients than their predecessors, resulting in the burden of clinical work being
      transferred to senior clinicians, representing a shift away from the traditional
      model of service delivery. This study charts the work rate trends among junior
      doctors and the proportion of work performed by senior doctors over a 3-year
      period. RESULTS: The number of patients seen by junior trainees fell by 4% and
      was associated with a statistically significant 16.6% reduction in the mean
      number of patients seen per hour. The number of patients seen purely by senior
      clinicians increased to over 35%, in addition to reviewing those seen by junior
      trainees. This highlights reduced clinical exposure and productivity among
      juniors, but also shows the significant knock-on effect on the workload of senior
      clinicians. CONCLUSIONS: There will need to be an increase in the number of
      trained clinicians within emergency medicine to continue to deliver effective
      training and supervision and ensure a safe, good quality service to patients.

PMID- 20156859
TI  - Potential and limitations of e-learning in emergency medicine.
AB  - This paper describes the potential benefits, pitfalls and barriers to adopting e
      learning in emergency medicine. While the benefits relating to access, engagement
      and quality assurance are clear, caution is urged in embracing e-learning for e
      learning's sake. It is argued that, if educational strategies are to change, this
      must be to the benefit of learners and not just for the convenience of access or
      record keeping. A variety of e-learning approaches are available, but those that
      promote group discussion or provide feedback from an educator are more likely to
      lead to successful learning than stand-alone feedback-free modules. A blended
      approach to learning is advocated where e-learning opportunities form an
      important but limited part of the overall educational experience. Shop floor and
      workshop-based teaching should be enhanced with e-learning, not replaced by it.

PMID- 20156860
TI  - Blood urea nitrogen and creatinine levels at admission for mortality risk
      assessment in patients with acute coronary syndromes.
AB  - PURPOSE: To compare the prognostic significance of blood urea nitrogen (BUN)
      versus creatinine levels for estimating the risk of death in patients with acute
      coronary syndrome (ACS). METHODS AND RESULTS: A prospective study of all patients
      admitted with suspected (n=1613) and retrospectively confirmed (n=54) myocardial
      infarction or unstable angina was conducted. The ROC analysis established that
      the area under the curve for BUN was higher than that of creatinine: 0.76 (95% CI
      0.70 to 0.82) and 0.69 (95% CI 0.63 to 0.76), respectively (p=0.005). The
      threshold level (that maximised the combined sensitivity and specificity) was 8.8
      mmol/l for BUN and 110 mumol/l for creatinine. Sensitivity (true positive cases)
      was 60% and 55% for threshold levels of BUN and creatinine, respectively, and
      specificity (true negative cases) was 82% and 77%, respectively. An increase of
      only BUN levels and a combination of increased BUN and creatinine levels, but not
      isolated hypercreatinaemia, proved to be the independent risk factors of death
      from ACS. Separate inclusion of BUN and creatinine as continuous variables in the
      regression model showed that both were associated with the risk of death: OR 1.22
      (95% CI 1.17 to 1.28) and 1.016 (95% CI 1.011 to 1.021) per unit increase
      (R(2)=14.5 and 8.4%, respectively). When both were simultaneously included, only
      an increased BUN level was pertinent to the prognosis of ACS: OR after
      multivariate adjustment 1.17 (95% CI 1.08 to 1.27). CONCLUSION: An increased
      level of BUN is a more significant risk factor for ACS outcomes than that of
      creatinine.

PMID- 20156861
TI  - Initially unsuspected hydropneumothorax following cardiac arrest.

PMID- 20156862
TI  - Variability in management of early severe sepsis.
AB  - OBJECTIVE: A study was undertaken to characterise how doctors in emergency
      medicine (EM), acute medicine (AM) and critical care (ICU) in the UK, USA and
      Australia and New Zealand (ANZ) approach the initial resuscitative care of
      patients with severe sepsis. METHODS: In 2007, members on the mailing lists of
      UK, US and ANZ EM, ICU and AM specialist organisations were invited to answer an
      anonymous scenario-based online survey. Respondents described their management of
      a patient with pneumonia and signs of sepsis. Multiple-choice questions were
      based on the Surviving Sepsis Campaign (SSC) 6-hour resuscitation bundle
      guidelines while avoiding the specific terms "sepsis" and "SSC guidelines".
      RESULTS: The response rate was 21% (2461/11 795). Only two respondents (0.1%)
      complied with all SSC resuscitation recommendations. Inter-specialty and inter
      country variations included differences in reporting initial lactate measurement
      (ranging from 30% in US-EM to 79% in UK-EM), fluid resuscitation targeting a
      central venous pressure of 8-12 mm Hg (from 15% in ANZ-ICU to 60% in UK-EM),
      blood transfusion for a central venous oxygen saturation <70% and haematocrit
      <30% (from 15% in ANZ-ICU to 70% in US-EM and UK-EM) and insertion of invasive
      monitoring (intra-arterial catheter: 89% in UK-ICU vs 20% in US-EM; central
      venous catheter: 83% in UK-ICU vs 44% in US-EM). 81% of respondents identified at
      least one reason why they did not implement all the recommendations; the reasons
      varied by region and specialty. CONCLUSIONS: Reported management of early sepsis
      varies between specialities and countries, and the responses do not follow SSC
      guidelines. Concerns relate to knowledge, attitudes and resources.

PMID- 20156863
TI  - Emergency physician interpretation of head CT in trauma and suspected
      subarachnoid haemorrhage--is it viable? An audit of current practice.
AB  - BACKGROUND AND OBJECTIVES: The number of emergency CT head examinations has
      increased since the introduction of the National Institute for Health and
      Clinical Excellence (NICE) head injury guidelines. In addition, government
      targets and changes to medical training impact on how services are delivered. In
      this context, emergency physicians may have a role to play in the interpretation
      of CT head images. We have provided such a service for 10 years and set out to
      audit our practice to establish whether our service is safe, the nature and
      clinical impact of any errors and whether a similar model may be applicable
      elsewhere. METHOD: Audit of emergency department patients over a 27-week period
      comparing immediate emergency physician interpretation of unenhanced CT head
      images for trauma or suspected subarachnoid haemorrhage (SAH) with the subsequent
      neuroradiology report. The clinical significance of any discordance was assessed.
      RESULTS: CT head interpretations in 9/442 (2%) of trauma and 1/48 (2.1%) of
      suspected SAH were discordant requiring a change clinical management had the
      formal neuroradiology report been available immediately. Specialist advice was
      sought in a further 77 patients. 1/634 of the total sample came to harm.
      CONCLUSION: The majority of CT head imaging scans can be interpreted safely by
      emergency physicians in trauma and suspected subarachnoid haemorrhage. We believe
      a safe and viable clinical service is provided and such a model is applicable in
      other centres.

PMID- 20156864
TI  - Use of recombinant factor VIIA for control of combat-related haemorrhage.
AB  - BACKGROUND: Recombinant activated human coagulation factor VII (rFVIIa), an
      intravascular strategy to promote clotting, is being used as an adjunct to
      surgical control of bleeding in combat trauma patients. OBJECTIVE: To describe
      the initial experiences with rFVIIa administered to combat casualties at US Navy
      Marine Corps medical treatment facilities in Iraq, and to compare survival
      outcomes of those treated with rFVIIa to controls not receiving rFVIIa. METHODS:
      Medical encounter data from the US Navy-Marine Corps Combat Trauma Registry were
      retrospectively reviewed to identify all battle-injured patients documented as
      having received rFVIIa during the period May 2004 to January 2006 of Operation
      Iraqi Freedom. Available clinical and injury related data are presented to
      characterise the patients. To assess effects of rFVIIa on survival outcomes,
      rFVIIa cases were matched to controls on injury severity and age. RESULTS: 22
      battle-injured patients from the Combat Trauma Registry received rFVIIa.
      Primarily young US Marines, these patients typically had penetrating injuries
      from improvised explosive devices and gunshot wounds. Injuries were often
      abdominal. The average dose used was similar to that reported in another study of
      civilian trauma patients, although dosing varies widely in the existing
      experimental and anecdotal literature. Over two-thirds (68%) of the rFVIIa
      patients survived-an identical outcome seen for a matched control group of 22
      patients. CONCLUSIONS: Survival of seriously injured combat casualties was good,
      although identical to that of a control group. Methodological limitations of this
      retrospective study preclude making firm conclusions about the effectiveness of
      rFVIIa. Future controlled studies are needed for safety and efficacy testing of
      rFVIIa in combat trauma patients.

PMID- 20156865
TI  - Ultrasound scan in the emergency department revealed rare but potentially
      dangerous internal jugular vein thrombosis.

PMID- 20156866
TI  - An audit of emergency medicine responses to children injured in violence.
AB  - AIM: To audit emergency department (ED) responses to violence in which children
      are injured in violence in a European capital city. METHODS: A prospective survey
      of children (aged <16 years) was conducted in Cardiff's only ED using ED software
      adapted for this purpose. All clinical records were scrutinised for evidence of
      discussion with and referral to agencies concerned with child protection.
      RESULTS: 123 children reportedly injured in violence (92 boys) were treated in
      2004, six aged 5-9 years; one under 5 years. Overall, 24 (19%) incidents had been
      reported to the police prior to ED arrival. Only four (3%) prompted documented
      referral or discussions with other agencies while in the ED. 78% prompted no
      action apart from treatment of injuries. 13 (10%) children had fractures or were
      admitted, but only two of these incidents had been drawn to police attention.
      Only five (4%) were injured at home; a large majority were injured in the street
      or at school with fists or feet (12 with a weapon) by other children or adults.
      CONCLUSIONS: In this audit, most violence in which children were injured took
      place in schools and in the street. For children of secondary school age, ED
      treatment rarely prompted referral or discussion with agencies responsible for
      child safety. Particularly since youth and child violence are major national
      issues, policy and practice in this area were developed and built on disclosure
      of all such cases to a single referral point in the local authority education
      department.

PMID- 20156867
TI  - A nurse-led 'first fitter' clinic in a paediatric emergency department: an
      experience.
AB  - BACKGROUND: The diagnoses of a child who presents to an Accident and Emergency
      (A&E) department with 'jerking' or loss of consciousness include an epileptic
      seizure, vasovagal event, cardiac syncope or other paroxysmal event. Where the
      likely diagnosis is a first epileptic tonic-clonic seizure, there is no consensus
      on how these children should be followed-up. This is important as many parents of
      children who experience an epileptic tonic-clonic seizure will be anxious and
      concerned about a recurrence and what to do if it does. A first fitter clinic
      (FFC) was established in the Accident and Emergency Department of our hospital to
      standardise the management of these children. METHODS: Children presenting to the
      A&E department of a large children's hospital considered to have had a first
      tonic-clonic epileptic seizure were offered an appointment for the FFC within 3
      weeks of their attendance. The clinic was supervised by an advanced nurse
      practitioner. Details of the child's reported tonic-clonic seizure were recorded
      on to a standardised proforma and additional information was obtained on other
      paroxysmal epileptic and non-epileptic events. RESULTS: Altogether, 120 children
      were offered an appointment in the FFC, of which 117 (97%) attended. Their mean
      age was 9.5 (range: 3.5-15.2)years. Following review in the clinic, 82 (70.1%) of
      the 117 children were considered to have experienced an epileptic tonic-clonic
      seizure. Twenty-eight patients were considered to have had a vaso-vagal attack or
      reflex anoxic seizure; two, a possible cardiac arrhythmia; two a breath-holding
      episode and in three patients the events could not be classified. CONCLUSION: The
      FFC was well-attended suggesting that families appreciated early follow-up and
      the opportunity to address their concerns and provide advice about what to do if
      there was a recurrence. The study also demonstrated that approximately one-third
      of children were misdiagnosed as having experienced a tonic-clonic seizure.

PMID- 20156868
TI  - Use of diffusion-weighted MRI in the emergency department for unconscious trauma
      patients with negative brain CT.
AB  - Diffusion-weighted MRI, a type of MR technique that can distinguish between
      cerebral fat embolism and diffuse axonal injury, is presented in this report.
      Emergency physicians should consider using diffusion-weighted imaging in
      unconscious trauma patients when their brain CT scans are unremarkable.

PMID- 20156869
TI  - Soft tissue injuries: Chapter 8 Forearm, hand and wrist.
AB  - Hand, wrist and forearm injuries are common presentations to the emergency
      department. There is a huge variation of severity from small lacerations
      involving only skin to extensive upper limb composite loss. There is no minor
      injury in upper limb trauma. Even the most trivial of wounds may be associated
      with major tendon or nerve damage which, if missed, may have life-long functional
      implications for the patient. Although this review concentrates on soft tissue
      injury and not bony injury, it is not possible to separate the two completely. It
      is important to realise that all fractures have a soft tissue injury component
      that needs to be assessed and correctly treated. In some instances the soft
      tissue component is much more important than the fracture, and failure to
      recognise it will result in a poor outcome.

PMID- 20156870
TI  - Best Evidence Topic report. BET 1. Are troponin levels indicated for the routine
      management of SVT?

PMID- 20156872
TI  - Best Evidence Topic report. BET 2. Is electrotherapy useful for tennis elbow?

PMID- 20156873
TI  - Best Evidence Topic report. BET 3. Is there a role for serum procalcitonin in the
      differentiation between septic and non-septic arthritis.

PMID- 20156874
TI  - Best Evidence Topic report. BET 4. What best scratches the itch?

PMID- 20156875
TI  - Improving medical students' understanding of prehospital care through a fourth
      year emergency medicine clerkship.
AB  - OBJECTIVES: The objective of this study was to survey medical students for a
      measurable opinion or knowledge increase in prehospital care after a fourth-year
      clerkship in emergency medicine (EM). The goal of the mandatory prehospital care
      aspect of the clerkship was twofold: to diminish the prehospital knowledge gap in
      medical school by teaching students about prehospital protocols and disaster
      medicine and to increase student interest. METHODS: The study setting was within
      a university-based academic EM department with a prehospital system of 250
      prehospital personnel. Data were collected from two similar questionnaires
      administered pre- and post-rotation to 49 fourth-year medical students.
      Statistical analyses were applied to collected data to quantify the changes of
      opinion and knowledge. Questions used a Likert five-point Scale. RESULTS: The
      data verified the improvement of students' knowledge in multiple areas of
      assessment. Greater than 35% opinion change (two points on the Likert Scale) was
      found in areas of prehospital care, 911 dispatch and education differences in
      prehospital providers (all p<0.0001; 95% CI 0.90 to 1.02, 0.66 to 0.90 and 0.66
      to 0.90, respectively). Greater than 35% opinion change was also found in
      understanding triage (p=0.03; 95% CI 0.29 to 0.58) and general teaching of
      prehospital care, fellowship opportunities and use of a monitor/defibrillator
      (p<0.0001, p<0.0001 and p=0.04, respectively). CONCLUSIONS: We found medical
      students developed a significantly improved understanding of prehospital care.
      Without extraordinary effort, academic emergency departments could easily include
      a significant experience and education within fourth-year EM clerkships.

PMID- 20156876
TI  - Investigation of paramedics' compliance with clinical practice guidelines for the
      management of chest pain.
AB  - BACKGROUND: Acute coronary syndromes remain a leading cause of preventable early
      deaths. However, previous studies have indicated that paramedics' compliance with
      chest pain protocols is suboptimal and that many patients do not receive the
      benefits of appropriate prehospital treatment. AIMS: To evaluate paramedics'
      level of compliance with national clinical practice guidelines and to investigate
      why, in certain circumstances, they may deviate from the clinical guidelines.
      SETTING: The Health Service Executive Mid-Western Regional Ambulance Service
      which serves a mixed urban and rural population across three counties in the west
      of Ireland. METHOD: A retrospective review of completed ambulance Patient Care
      Report Forms was conducted for all adult patients with non-traumatic chest pain
      treated between 1 December 2007 and 31 March 2008. During the same study period,
      paramedics were asked to complete a prospective questionnaire survey
      investigating the rationale behind their treatment decisions, their estimation of
      patient risk and their attitudes towards the clinical practice guidelines and
      training. RESULTS: 382 completed Patient Care Report Forms were identified for
      patients with chest pain, of whom 84.8% received ECG monitoring, 75.9% were given
      oxygen, 44.8% were treated with sublingual glyceryl trinitrate (GTN) and 50.8%
      were treated with aspirin. Only 20.4% of patients had a prehospital 12-lead ECG
      recorded. 58 completed questionnaires were returned (response rate 15%); 64% of
      respondents said they had received insufficient training to identify ECG
      abnormalities. CONCLUSIONS: Prehospital treatment with oxygen, aspirin,
      sublingual GTN and ECG monitoring remains underused by paramedics, even though
      only a small number of patients had documented contraindications to their use.
      The small number of patients who received a prehospital 12-lead ECG is a cause of
      particular concern and suggests that incomplete patient assessment may contribute
      to undertreatment. Further provision of training and equipment is necessary to
      enable paramedics to more accurately assess and treat patients with acute
      coronary syndromes.

PMID- 20156877
TI  - The McKesson prop--an essential tool for the emergency physician?
AB  - Facial trauma is a commonly encountered presentation to emergency departments.
      When associated airway compromise occurs, co-existing head and neck injuries
      serve to produce a challenging clinical situation. We describe two patients who
      suffered multi-system trauma, with severe maxillofacial injuries that
      necessitated prompt definitive airway management and mid-face stabilisation in
      the pre-hospital and emergency department phases of resuscitation. The McKesson
      prop is a simple yet highly effective tool for use in these injuries.

PMID- 20156878
TI  - Deliberate poisoning with dinitrophenol (DNP): an unlicensed weight loss pill.
AB  - A 46-year-old man took a lethal dose of an agent called dinitrophenol (DNP). He
      presented 11 h after ingestion with loin pain, diarrhoea and vomiting. He rapidly
      deteriorated with profound hyperthermia, acute renal failure, hyperkalaemia,
      metabolic acidosis and eventually haemodynamic instability. Despite aggressive
      supportive measures and rapid sequence induction, he deteriorated and died 21 h
      after ingestion. DNP is a metabolic poison that acts by uncoupling oxidative
      phosphorylation, leading to uncontrolled hyperthermia. It is an illegal weight
      loss agent that is used by body builders and is freely available on many internet
      websites. This case highlights the potential for patients to obtain and ingest
      exotic poisons. A summary of currently recommended treatment and a review of the
      literature on DNP is included, as well as a discussion of therapies that may be
      effective in treating hyperthermia in this situation.

PMID- 20156880
TI  - Coronary artery dissection: a management dilemma in the district general
      hospital.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial
      ischaemia with a high mortality. It most commonly occurs in young women with few
      risk factors for atherosclerosis. Presentation is varied, from sudden death to
      chest pain with features of myocardial ischaemia. The case presented highlights
      the dilemma of the need to treat a myocardial infarction within an acceptable
      time frame versus exploring a rare but entirely possible pathology, which may
      only be diagnosed in a tertiary referral centre a minimum of 90 min away.

PMID- 20156882
TI  - Impaired voluntary neuromuscular activation limits muscle power in mobility
      limited older adults.
AB  - BACKGROUND: Age-related alterations of neuromuscular activation may contribute to
      deficits in muscle power and mobility function. This study assesses whether
      impaired activation of the agonist quadriceps and antagonist hamstrings,
      including amplitude- and velocity-dependent characteristics of activation, may
      explain differences in leg extension torque and power between healthy middle
      aged, healthy older, and mobility-limited older adults. METHODS: Torque, power,
      and electromyography were recorded during maximal voluntary leg extension trials
      across a range of velocities on an isokinetic dynamometer. RESULTS: Neuromuscular
      activation was similar between middle-aged and older healthy groups, with
      differences in torque and power explained predominantly by muscle size. However,
      the older mobility-limited group demonstrated marked impairment of torque, power,
      and agonist muscle activation, with the greatest deficits occurring at the
      fastest movement velocities. Agonist muscle activation was found to be strongly
      associated with torque output. CONCLUSIONS: Similar neuromuscular activation
      between the middle-aged and older healthy groups indicates that impaired
      voluntary activation is not an obligatory consequence of aging. However, the
      finding that the mobility-limited group exhibited impaired activation of the
      agonist quadriceps and concomitant deficits in torque and power output suggests
      that neuromuscular activation deficits may contribute to compromised mobility
      function in older adults.

PMID- 20156883
TI  - Luteotrophic effects of relaxin, chorionic gonadotrophin and FSH in common
      marmoset monkeys (Callithrix jacchus).
AB  - In early pregnant primates, relaxin (RLX) is highly upregulated within the corpus
      luteum (CL), suggesting that RLX may have an important role in the implantation
      of the blastocyst. Therefore, the aim of the present study was to investigate the
      local effects of RLX and gonadotrophins on the maintenance of the CL using an in
      vitro microdialysis system. CLs of common marmoset monkeys were collected by
      luteectomy during different stages of the luteal phase and early pregnancy. Each
      CL was perfused with either Ringer's solution alone or Ringer's solution
      supplemented with either porcine RLX (250, 500 and 1000 ng/ml) or gonadotrophins
      (50 IU/ml). Application of RLX provoked a significant luteal response of
      progesterone (P(4)) and oestradiol (E(2)) secretions during the mid-luteal phase
      (500 ng/ml: P(4) 54+/-42%, E(2) 24+/-11%; 1000 ng/ml: E(2) 16+/-13%), and
      especially during the late luteal phase (250 ng/ml: P(4) 53+/-10%; 500 ng/ml:
      P(4) 44+/-15%; 1000 ng/ml: P(4) 62+/-15%, E(2) 18+/-7%). The effects of RLX on
      steroid secretion were irrespective of the RLX dosages. While treatment with
      human chorionic gonadotrophin did not affect luteal steroid or RLX secretion, the
      application of FSH resulted in a significant increase in the secretion of both
      P(4) (20+/-8%) and E(2) (37+/-28%), and a prominent rise in RLX during early
      pregnancy. In conclusion, our results demonstrate that RLX and FSH have a
      luteotrophic function in the marmoset monkeys; moreover, FSH has a function
      beyond its traditional role just as a follicle-stimulating hormone.

PMID- 20156884
TI  - Induction of progesterone receptor A form attenuates the induction of cytosolic
      phospholipase A2alpha expression by cortisol in human amnion fibroblasts.
AB  - Cytosolic phospholipase A2alpha (cPLA(2alpha), now known as PLA2G4A) is the
      enzyme catalyzing the formation of the rate-limiting substrate, arachidonic acid,
      for prostaglandin (PG) synthesis. The increasing expression of PLA2G4A toward
      term gestation in human amnion fibroblasts is believed to be the crucial event in
      parturition. Human amnion fibroblasts produce cortisol, progesterone and express
      glucocorticoid receptor (GR), progesterone receptor A (PGRA) form at term. The
      roles of progesterone and PGRA in the induction of PLA2G4A by cortisol via GR in
      the amnion fibroblasts remain largely unknown. Using cultured human term amnion
      fibroblasts, we found that cortisol induced the expression of PGRA, which was
      attenuated by inhibiting PG synthesis with indomethacin. Knockdown of PGRA
      expression or inhibition of endogenous progesterone production with trilostane
      significantly enhanced the induction of PLA2G4A by cortisol, whereas
      overexpression of PGRA attenuated the induction of PLA2G4A by cortisol. Although
      exogenous progesterone did not alter PLA2G4A expression under basal conditions,
      it attenuated cortisol-induced PLA2G4A expression at concentrations about tenfold
      higher, which might be achieved by competition with cortisol for GR. In
      conclusion, PGRA in the presence of endogenous progesterone is a transdominant
      repressor of the induction of PLA2G4A by cortisol. High level of progesterone may
      compete with cortisol for GR, thus further inhibiting the induction of PLA2G4A by
      cortisol. Moreover, increased PG synthesis by cortisol may feed back on the
      expression of PGRA leading to attenuation of cortisol-induced PLA2G4A expression.
      The above findings may be pertinent to the inconsistent effects of
      glucocorticoids on parturition in humans.

PMID- 20156885
TI  - The role of comorbidity in explaining the associations between anxiety disorders
      and smoking.
AB  - INTRODUCTION: Research has generally found strong associations between smoking
      and anxiety disorders. The present study sought to examine the role of
      comorbidity in explaining these relationships. METHODS: Participants from the
      National Comorbidity Survey-Replication (N = 5,692) were included in the present
      study. Axis I disorders were assessed using the World Mental Health Survey
      Initiative version of the World Health Organization Composite International
      Diagnostic Interview. In addition, smoking and mental health treatment history
      were assessed. RESULTS: Multivariate analyses covarying for demographic variables
      and psychiatric and substance use comorbidity found that posttraumatic stress
      disorder was uniquely associated with every smoking outcome of interest,
      including 12-month and lifetime daily and heavy smoking, nicotine dependence, and
      cessation failure. Generalized anxiety disorder and social anxiety disorder were
      associated with fewer smoking-related outcomes, and contrary to predictions,
      panic disorder was only independently associated with 12-month daily smoking.
      Panic attack history, however, was uniquely associated with 12-month daily and
      heavy smoking, nicotine dependence, and lifetime cessation failure. In addition,
      analyses indicated that greater number of anxiety disorders was associated with
      greater prevalence of each smoking outcome, and the presence of even one anxiety
      disorder was associated with elevated smoking prevalence. DISCUSSION: Several
      specific anxiety disorders were found to be uniquely associated with smoking
      behavior. Findings suggest that comorbidity may only explain the associations
      with smoking difficulties for some anxiety disorders.

PMID- 20156886
TI  - Cigarette smoking and subsequent hospitalization in a cohort of young U.S. Navy
      female recruits.
AB  - INTRODUCTION: Tobacco use is of particular concern to the U.S. Department of
      Defense because the military historically has had higher and heavier rates of
      tobacco use than civilians. Few prospective studies have examined the association
      of cigarette smoking with medical outcomes, particularly among initially healthy
      female military personnel. METHODS: This prospective cohort study followed over
      5,000 young U.S. Navy female recruits varying in their smoking status at entry
      into the Navy and collected their subsequent hospitalization data (i.e.,
      International Classification of Diseases, Ninth Revision codes) for up to 7-8
      years of service. RESULTS: Results indicated that after adjusting for differences
      in time at risk and sociodemographic variables, daily smokers (compared with
      never-and other smokers) had higher rates of hospitalization for any reason and
      for musculoskeletal conditions. Daily smokers also had higher rates than never-
      and other smokers for non-pregnancy-related hospitalizations and for mental
      disorders, although only the daily/other differences reached statistical
      significance. Daily smokers' average number of days hospitalized was
      significantly longer than that of never- and other smokers. DISCUSSION: Results
      suggest that young women do not have to wait decades to experience the harmful
      effects of smoking. A recent history of cigarette smoking is an important
      determinant of hospitalization risk for even young healthy women in the U.S.
      Navy.

PMID- 20156887
TI  - Predictors of smoking in cars with nonsmokers: findings from the 2007 Wave of the
      International Tobacco Control Four Country Survey.
AB  - OBJECTIVE: This study examines the proportion and characteristics of smokers who
      smoke in cars with nonsmokers across four countries and the potentially
      modifiable correlates of this behavior. METHODS: Respondents included a total of
      6,786 current adult smokers from Wave 6 (September 2007-February 2008) of the
      International Tobacco Control Four Country Survey, a random digit-dial telephone
      survey of nationally representative samples of adult smokers in Australia, the
      United Kingdom, Canada, and the United States. RESULTS: Reports of smoking in
      cars with nonsmokers ranged from a low of 29% in Australia and the United
      Kingdom, to 34% in Canada, and to a high of 44% in the United States. Daily
      smokers who were from the United States, male, and younger were the most likely
      to smoke in cars with nonsmokers. Several potentially modifiable factors were
      also found to be related to this behavior, including smoke-free homes and beliefs
      about the dangers of cigarette smoke exposure to nonsmokers. CONCLUSIONS: A
      considerable proportion of smokers continue to smoke in cars with nonsmokers
      across the four countries, particularly in the United States. Public health
      campaigns should educate smokers about the hazards of cigarette smoke exposure
      and promote the need for smoke-free cars. These findings provide a foundation of
      evidence relevant for jurisdictions that are considering banning smoking in cars.

PMID- 20156888
TI  - Affinity maturation of human botulinum neurotoxin antibodies by light chain
      shuffling via yeast mating.
AB  - Botulism is caused by the botulinum neurotoxins (BoNTs), the most poisonous
      substance known. Because of the high potency of BoNT, development of diagnostic
      and therapeutic antibodies for botulism requires antibodies of very high
      affinity. Here we report the use of yeast mating to affinity mature BoNT
      antibodies by light chain shuffling. A library of immunoglobulin light chains was
      generated in a yeast vector where the light chain is secreted. The heavy chain
      variable region and the first domain of the constant region (V(H)-C(H)1) from a
      monoclonal antibody was cloned into a different yeast vector for surface display
      as a fusion to the Aga2 protein. Through yeast mating of the two haploid yeasts,
      a library of light chain-shuffled Fab was created. Using this approach, the
      affinities of one BoNT/A and two BoNT/B scFv antibody fragments were increased
      from 9- to more than 77-fold. Subcloning the V-genes from the affinity-matured
      Fab yielded fully human IgG1 with equilibrium binding constants for BoNT/A and
      BoNT/B of 2.51 x 10(-11) M or lower for all three monoclonal antibodies. This
      technique provides a rapid route to antibody affinity maturation.

PMID- 20156889
TI  - The lure of treatment: expanded newborn screening and the curious case of
      histidinemia.

PMID- 20156890
TI  - What will it take for our society to value childhood oral health?

PMID- 20156891
TI  - Attitudes and practices of cardiologists and surgeons who manage HLHS.
AB  - OBJECTIVE: We conducted a survey to determine which management options pediatric
      cardiologists and cardiac surgeons in North America discuss and recommend when
      counseling parents after the diagnosis of hypoplastic left heart syndrome (HLHS).
      METHODS: Pediatric cardiologists and cardiac surgeons across North America were
      asked to complete an anonymous, Internet-based survey about their attitudes and
      practices regarding the management of HLHS. RESULTS: We contacted 1621 pediatric
      cardiologists and surgeons, of whom 749 (46%) completed the survey. When
      counseling parents of newborns with HLHS, 99.7% of respondents discussed staged
      palliative surgery, 67% discussed cardiac transplantation, and 62.2% discussed
      compassionate care without surgery. Only a minority (14.9%) discussed all of
      those options. Staged palliative surgery was recommended over cardiac
      transplantation or compassionate care without surgery by 76.2% of respondents.
      When counseling parents after prenatal diagnosis of HLHS, 98.8% of respondents
      discussed continuation of pregnancy with staged palliative surgery after birth,
      53.5% discussed continuation of pregnancy with cardiac transplantation after
      birth, 56.9% discussed continuation of pregnancy with compassionate care after
      birth, and 74.3% discussed termination of pregnancy. Only 36.5% discussed all of
      those options. Continuation of pregnancy with staged palliative surgery after
      birth was recommended over the other options by 56% of respondents. CONCLUSIONS:
      Virtually all North American pediatric cardiologists and cardiac surgeons
      surveyed discuss a surgical intervention when counseling parents about the care
      of their child or fetus with HLHS. However, only a minority discuss all options.
      Most physicians recommend staged palliative surgery for management of HLHS.

PMID- 20156892
TI  - Impact of gluten-free camp on quality of life of children and adolescents with
      celiac disease.
AB  - OBJECTIVE: A gluten-free camp allows children with celiac disease (CD) to enjoy a
      camp experience without concern and preoccupation with foods they eat or the
      stigma of their underlying disease. The objective of this study was to evaluate
      the impact of gluten-free camp on quality-of-life indicators for children and
      adolescents with CD. METHODS: Children aged 7 to 17 years with CD were
      administered a 14-question survey at the beginning and the end of a 7-day gluten
      free camp. Surveys used a Likert scale to examine general well-being, emotional
      outlook, and self-perception for the week before each survey. Differences between
      the time points were compared. Data were analyzed by paired t test. RESULTS: Of
      the 104 campers who attended camp, 77 (21 male) completed the survey at both time
      points. Most (70%) had been on a gluten-free diet (GFD) for <4 years. All seemed
      to benefit from camp, no longer feeling different from other kids or feeling
      frustrated with a restricted diet. A more beneficial impact was found for campers
      who were on a GFD for <4 years. Overall, campers reported an improvement in 11 of
      14 questions, statistically significant (P < .05) for 8 of those 11 questions.
      Improvement was observed in each of the 3 categories of questions: well-being,
      self-perception, and emotional outlook. CONCLUSIONS: Children who had CD and
      attended a week-long gluten-free camp demonstrated improvement in well-being,
      self-perception, and emotional outlook. The positive effects of camp were more
      apparent among campers who had been on a GFD for <4 years compared with those who
      had been on a GFD for > or =4 years, suggesting an adaptation to CD with time. A
      gluten-free camp that provides an environment of unrestricted foods can at least
      temporarily alleviate stress and anxiety around food and social interactions.
      Durability of these observations on return to daily life requires additional
      study.

PMID- 20156893
TI  - Importance of colonization site in the current epidemic of staphylococcal skin
      abscesses.
AB  - OBJECTIVE: The goal was to compare rectal and nasal Staphylococcus aureus
      colonization rates and S aureus pulsed-field types (PFTs) for children with S
      aureus skin and soft-tissue abscesses and normal control subjects. METHODS: Sixty
      consecutive children with S aureus skin and soft-tissue abscesses that required
      surgical drainage and 90 control subjects were enrolled. Cultures of the nares
      and rectum were taken in both groups. S aureus isolates from all sites were
      characterized through multiple-locus, variable-number, tandem-repeat analysis,
      pulsed-field gel electrophoresis, staphylococcal cassette chromosome mec typing
      for methicillin-resistant S aureus isolates, and determination of the presence of
      Panton-Valentine leukocidin genes. RESULTS: S aureus was detected significantly
      more often in the rectum of children with abscesses (47%) compared with those in
      the control group (1%; P = .0001). Rates of nasal colonization with S aureus were
      equivalent for children with abscesses (27%) and control subjects (20%; P = .33).
      S aureus recovered from the rectum was identical to S aureus in the abscess in
      88% of cases, compared with 75% of nasal isolates. PFT USA300, staphylococcal
      cassette chromosome mec type IV, and Panton-Valentine leukocidin genes were
      significantly increased in the S aureus isolates from children with abscesses
      compared with those from control subjects. CONCLUSIONS: Skin and soft-tissue
      abscesses in the current epidemic of community-associated staphylococcal disease
      are strongly associated with rectal colonization by PFT USA300. Nasal
      colonization in children does not seem to be a risk factor.

PMID- 20156894
TI  - Case-control study of neurodevelopment in deformational plagiocephaly.
AB  - OBJECTIVE: We assessed the neurodevelopment of infants with and without
      deformational plagiocephaly (DP), at an average age of 6 months. METHODS: The
      Bayley Scales of Infant Development III (BSID-III) were administered to 235 case
      subjects and 237 demographically similar, control participants. Three-dimensional
      head photographs were randomized and rated for severity of deformation by 2
      craniofacial dysmorphologists who were blinded to case status. RESULTS: We
      excluded 2 case subjects with no photographic evidence of DP and 70 control
      subjects who were judged to have some degree of DP. With control for age, gender,
      and socioeconomic status, case subjects performed worse than control subjects on
      all BSID-III scales and subscales. Case subjects' average scores on the motor
      composite scale were approximately 10 points lower than control subjects' average
      scores (P < .001). Differences for the cognitive and language composite scales
      were approximately 5 points, on average (P < .001 for both scales). In subscale
      analyses, case subjects' gross-motor deficits were greater than their fine-motor
      deficits. Among case subjects, there was no association between BSID-III
      performance and the presence of torticollis or infant age at diagnosis.
      CONCLUSIONS: DP seems to be associated with early neurodevelopmental
      disadvantage, which is most evident in motor functions. After follow-up
      evaluations of this cohort at 18 and 36 months, we will assess the stability of
      this finding. These data do not necessarily imply that DP causes
      neurodevelopmental delay; they indicate only that DP is a marker of elevated risk
      for delays. Pediatricians should monitor closely the development of infants with
      this condition.

PMID- 20156895
TI  - The infant car seat challenge: determining and managing an "abnormal" result.

PMID- 20156896
TI  - Team training in the neonatal resuscitation program for interns: teamwork and
      quality of resuscitations.
AB  - OBJECTIVE: Poor communication and teamwork may contribute to errors during
      neonatal resuscitation. Our objective was to evaluate whether interns who
      received a 2-hour teamwork training intervention with the Neonatal Resuscitation
      Program (NRP) demonstrated more teamwork and higher quality resuscitations than
      control subjects. METHODS: Participants were noncertified 2007 and 2008 incoming
      interns for pediatrics, combined pediatrics and internal medicine, family
      medicine, emergency medicine, and obstetrics and gynecology (n = 98). Pediatrics
      and combined pediatrics/internal medicine interns were eligible for 6-month
      follow-up (n = 34). A randomized trial was conducted in which half of the
      participants in the team training arm practiced NRP skills by using high-fidelity
      simulators; the remaining practiced with low-fidelity simulators, as did control
      subjects. Blinded, trained observers viewed video recordings of high-fidelity
      simulated resuscitations for teamwork and resuscitation quality. RESULTS: High
      fidelity training (HFT) group had higher teamwork frequency than did control
      subjects (12.8 vs 9.0 behaviors per minute; P < .001). Intervention groups
      maintained more workload management (control subjects: 89.3%; low-fidelity
      training [LFT] group: 98.0% [P < .001]; HFT group: 98.8%; HFT group versus
      control subjects [P < .001]) and completed resuscitations faster (control
      subjects: 10.6 minutes; LFT group: 8.6 minutes [P = .040]; HFT group: 7.4
      minutes; HFT group versus control subjects [P < .001]). Overall, intervention
      teams completed the resuscitation an average of 2.6 minutes faster than did
      control subjects, a time reduction of 24% (95% confidence interval: 12%-37%).
      Intervention groups demonstrated more frequent teamwork during 6-month follow-up
      resuscitations (11.8 vs 10.0 behaviors per minute; P = .030). CONCLUSIONS:
      Trained participants exhibited more frequent teamwork behaviors (especially the
      HFT group) and better workload management and completed the resuscitation more
      quickly than did control subjects. The impact on team behaviors persisted for at
      least 6 months. Incorporating team training into the NRP curriculum is a feasible
      and effective way to teach interns teamwork skills. It also improves simulated
      resuscitation quality by shortening the duration.

PMID- 20156897
TI  - Are patient-held vaccination records associated with improved vaccination
      coverage rates?
AB  - OBJECTIVE: The goal was to determine whether patient-held vaccination records
      improve vaccination rates. METHODS: The public-use files of the 2004-2006
      National Immunization Survey, a national, validated survey of households with
      children 19 to 35 months of age, were used. The main outcome was up-to-date (UTD)
      vaccination status (4 diphtheria-tetanus-acellular pertussis/diphtheria-tetanus
      vaccine, 3 poliovirus vaccine, 1 measles vaccine, 3 Haemophilus influenza type B
      vaccine, and 3 hepatitis B vaccine doses), and the main predictor was the use of
      a vaccination record. Control variables were race/ethnicity, maternal education,
      poverty status, language, number of children in the home, state of residence, and
      number of health care providers. RESULTS: Overall, 80.8% of children were UTD,
      and 40.8% of children had vaccination records. Children with vaccination records
      were more likely to be UTD (83.9% vs 78.6%; P < .0001). The largest effects
      associated with vaccination records were seen for children with multiple
      providers, comparing with and without a vaccination record (82.8% vs 71.9%; P <
      .0001), those with low maternal education, (81.6% vs 72.9%; P < .0001), and those
      with > or =4 children in the household, (76% vs 69.6%; P < .004). Logistic
      regression predicting UTD status and controlling for race/ethnicity, maternal
      education, poverty level, language, number of children in the home, and number of
      vaccine providers revealed the vaccination record to be associated with a 62%
      increase in the odds of UTD status (odds ratio: 1.62 [95% confidence interval:
      1.49-1.77]). CONCLUSIONS: Use of patient-held vaccination records is an easily
      implemented strategy that is associated with increased immunization rates. A
      greater effect was seen in groups at risk for underimmunization. Methods to
      incorporate and to ensure effective use of these records should be implemented.

PMID- 20156898
TI  - Enhancing diagnostic accuracy among nonexperts through use of video cases.
AB  - OBJECTIVE: The goal was to determine whether the diagnostic accuracy of
      nonexperts in selected learning environments would improve with the use of
      patient video cases (PVCs). METHODS: We designed a stepwise, team-based, learning
      approach with a (1) text-based patient presentation, (2) first review of a PVC,
      (3) small-group discussion, (4) second review of a PVC, and (5) large-group
      discussion and listening to think-aloud modeling by a content expert. Four
      pediatric neurology PVCs were analyzed by 44 physicians. After each step, the
      diagnostic accuracy was assessed with a questionnaire with open-ended questions
      measuring the frequency of relevant diagnoses and clinical diagnostic reasoning
      processes. RESULTS: The first review of the PVC was followed by a large number of
      relevant clinical diagnostic reasoning processes. Small-group discussions and
      listening to a think-aloud procedure with an expert were particularly effective
      in increasing the diagnostic accuracy of the nonexperts. CONCLUSIONS: The
      diagnostic accuracy of nonexperts was clearly enhanced by interaction in small
      group discussions and subsequent listening to a think-aloud procedure with a
      content expert. Learning through PVCs in clinical settings thus is improved
      through the interactive participation of junior and senior clinicians. Such an
      environment (a "virtual examination room") may be introduced at grand rounds,
      case conferences, or morning rounds, to stimulate the development of diagnostic
      accuracy in nonexperts.

PMID- 20156900
TI  - Introducing historical perspectives.

PMID- 20156899
TI  - Accuracy of depression screening tools for identifying postpartum depression
      among urban mothers.
AB  - OBJECTIVE: The goal was to describe the accuracy of the Edinburgh Postnatal
      Depression Scale (EPDS), Beck Depression Inventory II (BDI-II), and Postpartum
      Depression Screening Scale (PDSS) in identifying major depressive disorder (MDD)
      or minor depressive disorder (MnDD) among low-income, urban mothers attending
      well-child care (WCC) visits during the postpartum year. METHODS: Mothers (N =
      198) attending WCC visits with their infants 0 to 14 months of age completed a
      psychiatric diagnostic interview (standard method) and 3 screening tools. The
      sensitivities and specificities of each screening tool were calculated in
      comparison with diagnoses of MDD or MDD/MnDD. Receiver operating characteristic
      curves were calculated and the areas under the curves for each tool were compared
      to assess accuracy for the entire sample (representing the postpartum year) and
      subsamples (representing early, middle, and late postpartum time frames). Optimal
      cutoff scores were calculated. RESULTS: At some point between 2 weeks and 14
      months after delivery, 56% of mothers met criteria for either MDD (37%) or MnDD
      (19%). When used as continuous measures, all scales performed equally well (areas
      under the curves of > or =0.8). With traditional cutoff scores, the measures did
      not perform at the expected levels of sensitivity and specificity. Optimal cutoff
      scores for the BDI-II (> or =14 for MDD and > or =11 for MDD/MnDD) and EPDS (> or
      =9 for MDD and > or =7 for MDD/MnDD) were lower than currently recommended. For
      the PDSS, the optimal cutoff score was consistent with current guidelines for MDD
      (> or =80) but higher than recommended for MDD/MnDD (> or =77). CONCLUSIONS:
      Large proportions of low-income, urban mothers attending WCC visits experience
      MDD or MnDD during the postpartum year. The EPDS, BDI-II, and PDSS have high
      accuracy in identifying depression, but cutoff scores may need to be altered to
      identify depression more accurately among urban, low-income mothers.

PMID- 20156901
TI  - Association between helicobacter pylori and gastrointestinal symptoms in
      children.
AB  - OBJECTIVE: Recurrent abdominal pain (RAP) and other gastrointestinal (GI)
      symptoms are common complaints among children. The role of Helicobacter pylori in
      the cause of these complaints remains controversial. Nevertheless, there is an
      increasing pressure on primary care clinicians to screen for H pylori infection
      in symptomatic children. We systematically reviewed the published evidence for an
      association between H pylori infection and GI symptoms in children. METHODS:
      Medline and Embase databases up to July 2009 were searched to identify studies
      that evaluated the association between H pylori and GI symptoms in children aged
      up to 18 years. When studies reported on abdominal pain without additional
      definition, thus not fulfilling Apley's criteria, we grouped these outcomes as
      unspecified abdominal pain (UAP). Methodologic quality was scored by using a
      standardized list of criteria, and crude odds ratios (ORs) with 95% confidence
      intervals (CIs) were calculated and pooled. RESULTS: Thirty-eight studies met our
      inclusion criteria: 23 case-control studies, 14 cross-sectional studies, and 1
      prospective cohort study. The overall methodologic quality was low. Pooled ORs
      for the association between RAP and H pylori infection in children were 1.21 (95%
      CI: 0.82-1.78) in 12 case-control studies and 1.00 (95% CI: 0.76-1.31) in 7 cross
      sectional studies. Meta-analysis of the association between UAP and H pylori
      infection in 6 hospital-based studies resulted in a pooled OR of 2.87 (95% CI:
      1.62-5.09) compared with 0.99 (95% CI: 0.46-2.11) in 5 population-based studies.
      Two of 3 studies concerning epigastric pain reported a statistically significant
      positive association with H pylori infection. CONCLUSIONS: We found no
      association between RAP and H pylori infection in children and conflicting
      evidence for an association between epigastric pain and H pylori infection. We
      found evidence for an association between UAP but could not confirm this finding
      in children seen in primary care.

PMID- 20156902
TI  - Performance of a rapid influenza test in children during the H1N1 2009 influenza
      a outbreak.
AB  - OBJECTIVE: To evaluate the performance of a rapid influenza diagnostic test
      (RIDT) in detecting H1N1 2009 influenza A virus in respiratory samples from
      pediatric patients in comparison to that of real-time reverse-transcriptase
      polymerase chain reaction (rRT-PCR) and viral culture. Methodology. This was a
      cross-sectional diagnostic-accuracy study conducted at a tertiary care children's
      hospital. Patients for whom the RIDT (BinaxNOW [Binax, Inc, Portland, ME]), viral
      culture, and rRT-PCR results were known were included. Sensitivity, specificity,
      and likelihood ratios (LRs) were calculated. RESULTS: A total of 3030 specimens
      had RIDT results paired with both rRT-PCR and viral culture results. With rRT-PCR
      as the reference, overall test sensitivity was 45% (95% confidence interval [CI]:
      43.3%-46.3%) and specificity was 98.6% (95% CI: 98.1%-99%). Positive and negative
      LRs were 32.9 (95% CI: 22.9-45.4) and 0.56 (95% CI: 0.54-0.58), respectively.
      RIDT sensitivity was significantly higher in young infants and children younger
      than 2 years than in older children. Using viral culture as the reference
      standard, RIDT sensitivity was 55.5% (95% CI: 51.9%-95.6%) and specificity was
      95.6% (95% CI: 95%-96.1%). The positive and negative LRs were 12.6 and 0.47,
      respectively. CONCLUSIONS: The RIDT had relatively poor sensitivity but excellent
      specificity in this consecutive series of respiratory specimens obtained from
      pediatric patients. Although a positive RIDT result was highly accurate in
      predicting infection with influenza type A H1N1 2009 in children, a negative RIDT
      result did not preclude a child having H1N1. Therefore, for children at high risk
      with influenza-like illnesses during high-prevalence periods of influenza,
      empiric initiation of antiviral therapy should be considered for patients with a
      negative RIDT result.

PMID- 20156903
TI  - Worldwide timing of growth faltering: revisiting implications for interventions.
AB  - OBJECTIVE: Our goal was to describe worldwide growth-faltering patterns by using
      the new World Health Organization (WHO) standards. METHODS: We analyzed
      information available from the WHO Global Database on Child Growth and
      Malnutrition, comprising data from national anthropometric surveys from 54
      countries. Anthropometric data comprise weight-for-age, length/height-for-age,
      and weight-for-length/height z scores. The WHO regions were used to aggregate
      countries: Europe and Central Asia; Latin America and the Caribbean; North Africa
      and Middle East; South Asia; and sub-Saharan Africa. RESULTS: Sample sizes ranged
      from 1000 to 47 000 children. Weight for length/height starts slightly above the
      standard in children aged 1 to 2 months and falters slightly until 9 months of
      age, picking up after that age and remaining close to the standard thereafter.
      Weight for age starts close to the standard and falters moderately until reaching
      approximately -1 z at 24 months and remaining reasonably stable after that.
      Length/height for age also starts close to the standard and falters dramatically
      until 24 months, showing noticeable bumps just after 24, 36, and 48 months but
      otherwise increasing slightly after 24 months. CONCLUSIONS: Comparison of child
      growth patterns in 54 countries with WHO standards shows that growth faltering in
      early childhood is even more pronounced than suggested by previous analyses based
      on the National Center for Health Statistics reference. These findings confirm
      the need to scale up interventions during the window of opportunity defined by
      pregnancy and the first 2 years of life, including prevention of low birth weight
      and appropriate infant feeding practices.

PMID- 20156904
TI  - Impact of labor on outcomes in transient tachypnea of the newborn: population
      based study.
AB  - OBJECTIVE: Our aim was to assess the effect of labor on the risk and course of
      transient tachypnea of the newborn (TTN) in term neonates from a contemporary,
      population-based cohort. METHODS: We analyzed perinatal characteristics of term
      singleton newborns (gestational age [GA] of > or =37 completed weeks) who were
      born between January 2001 and December 2005 in the federal states of Hesse and
      Saarland (Germany). TTN was diagnosed on the basis of International
      Classification of Diseases, 10th Revision codes. RESULTS: Of a total of 275 459
      births, 239 971 fulfilled the inclusion criteria of GA of > or =37 completed
      weeks and singleton live birth. Among those, 13 346 term infants were admitted
      for neonatal care and 1423 were diagnosed as having TTN. The overall incidence of
      TTN was 5.9 cases per 1000 singleton live births in our study cohort. Elective
      cesarean section, low GA, male gender, and low birth weight were associated with
      TTN. The duration of oxygen supplementation for newborns with TTN was associated
      inversely with the duration of labor (r = -0.151; P = .028). CONCLUSIONS: Our
      study indicates that TTN is strongly related to elective cesarean section and low
      GA. Furthermore, the absence of exposure to labor contractions is associated with
      increased risk and severe course of TTN at term, with longer duration of oxygen
      supplementation.

PMID- 20156905
TI  - Classic Kaposi sarcoma in 3 unrelated Turkish children born to consanguineous
      kindreds.
AB  - Infection by human herpesvirus 8 (HHV-8) in childhood is common in the
      Mediterranean basin; however, classic Kaposi sarcoma (KS) is exceedingly rare in
      children not infected with HIV and not receiving immunosuppression, with only 30
      cases having been reported since 1960. We recently reported 2 children with
      autosomal and X-linked recessive primary immunodeficiencies underlying KS in a
      context of multiple clinical manifestations. These reports suggested that classic
      KS in otherwise healthy children might also result from inborn errors of immunity
      more specific to HHV-8. In this article, we describe 3 unrelated Turkish children
      with classic KS born to first-cousin parents. The first patient, a girl,
      developed KS at 2 years of age with disseminated cutaneous and mucosal lesions.
      The clinical course progressed rapidly, and the patient died within 3 months
      despite treatment with vincristine. The other 2 children developed a milder form
      of KS at the age of 9 years, with multiple cutaneous lesions. A boy treated with
      interferon alpha therapy for 12 months is now in full remission at the age of 14,
      2 years after treatment. The second girl is currently stabilized with etoposide,
      which was begun 4 months ago. None of the 3 children had any relevant familial
      history or other clinical features. The occurrence of classic KS in 3 unrelated
      Turkish children, each born to consanguineous parents, strongly suggests that
      autosomal recessive predisposition may drive the rare occurrence of HHV-8
      associated classic KS in children.

PMID- 20156906
TI  - Sensitivity of rapid influenza diagnostic testing for swine-origin 2009 a (H1N1)
      influenza virus in children.
AB  - BACKGROUND: The rapidly evolving pandemic of novel 2009 swine-origin influenza A
      (H1N1) virus (S-OIV) demands that accurate and practical diagnostics be urgently
      evaluated for their potential clinical utility. OBJECTIVE: To determine the
      diagnostic accuracy of a rapid influenza diagnostic test (RIDT) and direct
      fluorescent antibody (DFA) assay for S-OIV by using reverse-transcription
      polymerase chain reaction (RT-PCR) as the reference standard. METHODS: We
      prospectively recruited children (aged 0-17 years) assessed in the emergency
      department of a pediatric referral hospital and a community pediatric clinic for
      influenza-like illness between May 22 and July 25, 2009. RIDT (performed on-site)
      and DFA were compared with RT-PCR to determine their sensitivity and specificity
      for S-OIV. We also compared the sensitivity of RIDT for S-OIV to that for
      seasonal influenza over 2 preceding seasons. RESULTS: Of 820 children enrolled,
      651 were from the emergency department and 169 were from the clinic. RIDT
      sensitivity was 62% (95% confidence interval [CI]: 52%-70%) for S-OIV, with a
      specificity of 99% (95% CI: 92%-100%). DFA sensitivity was 83% (95% CI: 75%-89%)
      and was superior to that of RIDT (P < .001). RIDT sensitivity for S-OIV was
      comparable to that for seasonal influenza when using DFA supplemented with
      culture as the reference standard. RIDT sensitivity for influenza viruses was
      significantly higher in children 5 years of age or younger (P = .003) and in
      patients presenting < or =2 days after symptom onset (P < .001). CONCLUSIONS: The
      sensitivity of RIDT for detection of S-OIV is higher than recently reported in
      mixed adult-pediatric populations but remains suboptimal.

PMID- 20156907
TI  - Concurrent risks in sudden infant death syndrome.
AB  - BACKGROUND: Despite improved education on safe sleep, infants are still exposed
      to multiple risks for sudden infant death syndrome (SIDS). Variability among
      health care providers continues to exist regarding knowledge of risk factors and
      the provision of education to caregivers. OBJECTIVE: To enhance the content and
      delivery of SIDS risk-reduction initiatives by physicians and other health care
      providers and to provide them with a context for evaluating their discussions of
      risks and compensatory strategies, we sought to raise awareness of the frequency
      of risk factors in SIDS cases, patterns of co-occurrence, associations between
      modifiable and nonmodifiable risks, and the rarity of cases without risk. DESIGN
      AND METHODS: In a population-based retrospective review of 244 (97%) New Jersey
      SIDS cases (1996-2000), we assessed the frequencies and co-occurrences of
      modifiable (maternal and paternal smoking, nonsupine sleep or prone status at
      discovery, bed-sharing, or scene risks) and nonmodifiable (upper respiratory
      infection or <37 weeks' gestational age) risks. RESULTS: Nonsupine sleep occurred
      in 70.4% of cases with data on position (159 of 226). Thirteen cases were of
      infants who were discovered prone, with an increased positional risk to 76.1%, in
      which 87% contained additional risks. Maternal smoking occurred in 42.6% (92 of
      216) of the cases with data on this risk, and 98% among those cases had
      additional risks. At least 1 risk was found in 96% of the cases, and 78% had 2 to
      7 risks. Of the 9 of 244 risk-free cases (3.7%), 7 lacked data on 2 to 5 risks
      per case. On the basis of the complete data, only 2 (0.8%) of all 244 cases were
      risk free. When nonmodifiable risks were excluded, 5.3% of the cases met this
      definition. CONCLUSIONS: Risk-free and single-risk SIDS cases are rare, and most
      contain multiple risks. Parent education should be comprehensive and address
      compensatory strategies for nonmodifiable risks.

PMID- 20156908
TI  - Lapatinib plus letrozole as first-line therapy for HER-2+ hormone receptor
      positive metastatic breast cancer.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of letrozole plus lapatinib
      versus letrozole plus placebo in women with hormone receptor (HR)(+) human
      epidermal growth factor receptor (HER)-2(+) tumors receiving first-line therapy
      for metastatic breast cancer (MBC). PATIENTS AND METHODS: Postmenopausal women (n
      = 1,286) with HR(+) MBC were randomized to daily oral treatment with letrozole
      (2.5 mg) plus lapatinib (1,500 mg) versus letrozole (2.5 mg) plus placebo. Of the
      1,286 patients enrolled in the phase III study, 219 had HER-2(+) tumors. The
      primary endpoint was progression-free survival (PFS) in HER-2(+) patients.
      RESULTS: Results in the HR(+) HER-2(+) population (n = 219) are presented. The
      addition of lapatinib to letrozole resulted in a significantly lower risk for
      disease progression than with letrozole alone (hazard ratio, 0.71; 95% confidence
      interval, 0.53-0.96). The PFS time was 8.2 months, versus 3.0 months. The
      objective response rate (ORR) (28% versus 15%) and clinical benefit rate (CBR)
      (48% versus 29%) were also significantly greater in lapatinib-treated women. The
      most common adverse events in the lapatinib group were diarrhea (68%) and rash
      (46%), primarily grade 1 and 2. CONCLUSIONS: The addition of lapatinib to
      letrozole is well tolerated and leads to a significantly greater PFS time, ORR,
      and CBR than with letrozole alone in women with MBC who coexpress HR and HER-2.

PMID- 20156909
TI  - Randomized phase III clinical trial of five different arms of treatment in 332
      patients with cancer cachexia.
AB  - PURPOSE: A phase III, randomized study was carried out to establish the most
      effective and safest treatment to improve the primary endpoints of cancer
      cachexia-lean body mass (LBM), resting energy expenditure (REE), and fatigue-and
      relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow
      Prognostic Score (GPS) and proinflammatory cytokines. PATIENTS AND METHODS: Three
      hundred thirty-two assessable patients with cancer-related anorexia/cachexia
      syndrome were randomly assigned to one of five treatment arms: arm 1,
      medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral
      supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4,
      thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment
      duration was 4 months. RESULTS: Analysis of variance showed a significant
      difference between treatment arms. A post hoc analysis showed the superiority of
      arm 5 over the others for all primary endpoints. An analysis of changes from
      baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed
      tomography) significantly increased in arm 5. REE decreased significantly and
      fatigue improved significantly in arm 5. Appetite increased significantly in arm
      5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern
      Cooperative Oncology Group performance status (ECOG PS) score decreased
      significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was
      comparable between arms. CONCLUSION: The most effective treatment in terms of all
      three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS,
      and ECOG PS score was the combination regimen that included all selected agents.

PMID- 20156910
TI  - Prophylaxis with systemic antibiotics in patients with severe burns.

PMID- 20156912
TI  - The impact of outcome reporting bias in randomised controlled trials on a cohort
      of systematic reviews.
AB  - OBJECTIVE: To examine the prevalence of outcome reporting bias-the selection for
      publication of a subset of the original recorded outcome variables on the basis
      of the results-and its impact on Cochrane reviews. DESIGN: A nine point
      classification system for missing outcome data in randomised trials was developed
      and applied to the trials assessed in a large, unselected cohort of Cochrane
      systematic reviews. Researchers who conducted the trials were contacted and the
      reason sought for the non-reporting of data. A sensitivity analysis was
      undertaken to assess the impact of outcome reporting bias on reviews that
      included a single meta-analysis of the review primary outcome. RESULTS: More than
      half (157/283 (55%)) the reviews did not include full data for the review primary
      outcome of interest from all eligible trials. The median amount of review outcome
      data missing for any reason was 10%, whereas 50% or more of the potential data
      were missing in 70 (25%) reviews. It was clear from the publications for 155 (6%)
      of the 2486 assessable trials that the researchers had measured and analysed the
      review primary outcome but did not report or only partially reported the results.
      For reports that did not mention the review primary outcome, our classification
      regarding the presence of outcome reporting bias was shown to have a sensitivity
      of 88% (95% CI 65% to 100%) and specificity of 80% (95% CI 69% to 90%) on the
      basis of responses from 62 trialists. A third of Cochrane reviews (96/283 (34%))
      contained at least one trial with high suspicion of outcome reporting bias for
      the review primary outcome. In a sensitivity analysis undertaken for 81 reviews
      with a single meta-analysis of the primary outcome of interest, the treatment
      effect estimate was reduced by 20% or more in 19 (23%). Of the 42 meta-analyses
      with a statistically significant result only, eight (19%) became non-significant
      after adjustment for outcome reporting bias and 11 (26%) would have overestimated
      the treatment effect by 20% or more. CONCLUSIONS: Outcome reporting bias is an
      under-recognised problem that affects the conclusions in a substantial proportion
      of Cochrane reviews. Individuals conducting systematic reviews need to address
      explicitly the issue of missing outcome data for their review to be considered a
      reliable source of evidence. Extra care is required during data extraction,
      reviewers should identify when a trial reports that an outcome was measured but
      no results were reported or events observed, and contact with trialists should be
      encouraged.

PMID- 20156913
TI  - Lichen sclerosus.

PMID- 20156911
TI  - Prophylactic antibiotics for burns patients: systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the evidence for prophylactic treatment with systemic
      antibiotics in burns patients. DESIGN: Systematic review and meta-analysis of
      randomised or quasi-randomised controlled trials recruiting burns inpatients that
      compared antibiotic prophylaxis (systemic, non-absorbable, or topical) with
      placebo or no treatment. DATA SOURCES: PubMed, Cochrane Library, LILACS, Embase,
      conference proceedings, and bibliographies. No language, date, or publication
      status restrictions were imposed. Review methods Two reviewers independently
      extracted data. The primary outcome was all cause mortality. Risk or rate ratios
      with 95% confidence intervals were pooled with a fixed effect model if no
      heterogeneity was present. RESULTS: 17 trials were included. Trials that assessed
      systemic antibiotic prophylaxis given for 4-14 days after admission showed a
      significant reduction in all cause mortality (risk ratio 0.54, 95% confidence
      interval 0.34 to 0.87, five trials). The corresponding number needed to treat was
      8 (5 to 33), with a control event rate of 26%. Perioperative non-absorbable or
      topical antibiotics alone did not significantly affect mortality. There was a
      reduction in pneumonia with systemic prophylaxis and a reduction in wound
      infections with perioperative prophylaxis. Staphylococcus aureus infection or
      colonisation was reduced with anti-staphylococcal antibiotics. In three trials,
      resistance to the antibiotic used for prophylaxis significantly increased (rate
      ratio 2.84, 1.38 to 5.83). The overall methodological quality of the trials was
      poor. CONCLUSIONS: Prophylaxis with systemic antibiotics has a beneficial effect
      in burns patients, but the methodological quality of the data is weak. As such
      prophylaxis is currently not recommended for patients with severe burns other
      than perioperatively, there is a need for randomised controlled trials to assess
      its use.

PMID- 20156914
TI  - GP is suspended for failing to tell partners about insolvency.

PMID- 20156917
TI  - Michelle Obama launches programme to combat US childhood obesity.

PMID- 20156915
TI  - Heroin contaminated with anthrax has killed 11 people.

PMID- 20156918
TI  - The financial burden of HIV care, including antiretroviral therapy, on patients
      in three sites in Indonesia.
AB  - This paper assesses the extent of the financial burden due to out-of-pocket
      payments for health care incurred by people living with HIV (PLHIV) and the
      effect of this burden on their financial capacity. Data were collected in a cross
      sectional survey of 353 PLHIV from three cities in Indonesia (Jakarta, Jogjakarta
      and Merauke). Respondents in Jakarta were sampled from one hospital and one non
      governmental organization working with PLHIV. In Jogjakarta and Merauke, all HIV
      patients on antiretroviral therapy (ART) who came to selected hospitals during
      the interview period were asked to participate in the survey. The survey
      collected data on the frequency and extent of payments for HIV-related care, with
      answers cross-checked against medical records. Results show that PLHIV had
      different burdens of payments in the different geographical areas. On average,
      respondents in Jogjakarta spent 68%, and PLHIV on ART in Jakarta spent 96%, of
      monthly expenditure for HIV-related care, indicating a substantial financial
      burden for many ART patients. These patients depended on several sources of
      finance to cover the costs of their care, with donations from their immediate
      family being the most common method, selling assets and payments from personal
      income being the second most common method in Jakarta and Jogjakarta,
      respectively. Most PLHIV in these two areas did not have insurance. In Merauke,
      there were little observed out-of-pocket payments because the government covers
      medical costs via the local budget and health insurance for the poor. The results
      of this study confirm previous findings that providing subsidized ART drugs alone
      does not ensure financial accessibility to HIV care. Thus, the government of
      Indonesia at central and local levels should consider covering HIV care
      additional to providing antiretroviral drugs free of charge. Social health
      insurance should also be encouraged.

PMID- 20156920
TI  - Willingness to pay for community-based health insurance in Nigeria: do economic
      status and place of residence matter?
AB  - OBJECTIVE: We examine socio-economic status (SES) and geographic differences in
      willingness of respondents to pay for community-based health insurance (CBHI).
      METHODS: The study took place in Anambra and Enugu states, south-east Nigeria. It
      involved a rural, an urban and a semi-urban community in each of the two states.
      A pre-tested interviewer-administered questionnaire was used to collect
      information from a total of 3070 households selected by simple random sampling.
      Contingent valuation was used to elicit willingness to pay (WTP) using the
      bidding game format. Data were examined for correlation between SES and
      geographic locations with WTP. Log ordinary least squares (OLS) was used to
      examine the construct validity of elicited WTP. RESULTS: Generally, less than 40%
      of the respondents were willing to pay for CBHI membership for themselves or
      other household members. The proportions of people who were willing to pay were
      much lower in the rural communities, at less than 7%. The average that
      respondents were willing to pay as a monthly premium for themselves ranged from
      250 Naira (US$1.7) in a rural community to 343 Naira (US$2.9) in an urban
      community. The higher the SES group, the higher the stated WTP amount. Similarly,
      the urbanites stated higher WTP compared with peri-urban and rural dwellers.
      Males and people with more education stated higher WTP values than females and
      those with less education. Log OLS also showed that previously paying out-of
      pocket for health care was negatively related to WTP. Previously paying for
      health care using any health insurance mechanism was positively related to WTP.
      CONCLUSION: Economic status and place of residence amongst other factors matter
      in peoples' WTP for CBHI membership. Consumer awareness has to be created about
      the benefits of CBHI, especially in rural areas, and the amount to be paid has to
      be augmented with other means of financing (e.g. government and/or donor
      subsidies) to ensure success and sustainability of CBHI schemes.

PMID- 20156921
TI  - Serum sclerostin levels negatively correlate with parathyroid hormone levels and
      free estrogen index in postmenopausal women.
AB  - CONTEXT: Sclerostin is a negative regulator of bone formation. OBJECTIVE: The aim
      of the study was to compare serum sclerostin levels in premenopausal and
      postmenopausal women and evaluate its relationship to estrogen, TH, bone
      turnover, and bone mass. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross
      sectional observational study of healthy community-dwelling pre- and
      postmenopausal women. INTERVENTION(S): There were no interventions. MAIN OUTCOME
      MEASURE(S): We compared serum sclerostin levels in pre- and postmenopausal women
      and correlated sclerostin levels with female sex hormones, calciotropic hormones,
      bone turnover markers, and bone mineral density. RESULTS: Premenopausal women
      were 26.8 yr old, and postmenopausal women were 56.8 yr old. Postmenopausal women
      had lower values for estradiol (30 +/- 23 vs. 10 +/- 4 pg/ml; P < 0.001), estrone
      (61 +/- 24 vs. 29 +/- 10 pg/ml; P <0.001), and free estrogen index (FEI) (6 +/- 4
      vs. 3 +/- 2 pmol/nmol; P = 0.008) and significantly lower bone mineral density at
      all sites compared to premenopausal women, with no significant differences in
      levels of PTH, 25-hydroxy or 1,25-dihydroxy vitamin D levels. Postmenopausal
      women had significantly higher serum sclerostin levels (1.16 +/- 0.38 ng/ml vs.
      0.48 +/- 0.15 ng/ml; P < 0.001). Because most of the premenopausal women were on
      oral contraceptives, subsequent analyses were limited to postmenopausal women.
      There were significant negative correlations between sclerostin and FEI and
      sclerostin and PTH in this group. Using multiple regression analysis, both FEI
      (beta = -0.629; P = 0.002) and PTH (beta = -0.554; P = 0.004) were found to be
      independent predictors of sclerostin levels in postmenopausal women. CONCLUSIONS:
      Our findings suggest that serum sclerostin levels are regulated by both estrogens
      and PTH in postmenopausal women. These findings need to be explored further in
      larger prospective studies.

PMID- 20156922
TI  - Are the clinical and pathological features of differentiated thyroid carcinoma
      really changed over the last 35 years? Study on 4187 patients from a single
      Italian institution to answer this question.
AB  - BACKGROUND: In the last decades, a marked increased prevalence of differentiated
      thyroid cancer (DTC) has been observed worldwide. The aim of this study was to
      evaluate the changing features of DTC referred to our institution between 1969
      and 2004. METHODS: Clinical and pathological features and prognostic factors were
      analyzed in 4187 DTC patients, subdivided into two groups: group 1 (n = 1215) and
      group 2 (n = 2972) diagnosed before and after 1990, respectively. RESULTS: Group
      2 showed an increased proportion of micropapillary carcinoma and a concomitant
      decrease of follicular histotype. Male percentage was greater in group 2, whereas
      median age at diagnosis was unchanged. DTC of group 2 were more frequently
      associated with multinodular goiter or autoimmune thyroiditis, but many were
      unexpected findings. Features of aggressiveness were significantly less frequent
      in group 2, and the survival rate was greater (98.7 vs. 91.4%, P < 0.0001).
      Gender, age, histotype, tumor size, extrathyroidal macroinvasion, and lymph node
      and/or distant metastases were found to be poor prognostic factors in both groups
      using univariate analysis, but with multivariate analysis, only advanced age
      (odds ratio = 22.52 for older patients) and advanced stage (odds ratio = 53.54
      for more advanced cases) were independently correlated with a lower survival.
      CONCLUSIONS: DTC patients diagnosed after 1990 have smaller tumors with less
      advanced stage and a better prognosis. The question of whether this is related to
      the finding of tumors with a low clinical penetrance or to the anticipation of
      diagnosis remains to be clarified. Despite these significant differences, both
      advanced stage and older age still represent the most important poor prognostic
      factors for survival.

PMID- 20156923
TI  - Circadian rhythm of serum vaspin in healthy male volunteers: relation to meals.
AB  - CONTEXT: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a
      novel adipokine with insulin-sensitizing effects. However, the physiological role
      for vaspin in human metabolic regulation remains to be established. OBJECTIVE: We
      studied the 24-h profiles of circulating vaspin concentrations in relation to
      meal ingestion in normal adults. DESIGN: Blood samples were drawn 39 times
      throughout a 24-h period from 10 healthy male subjects provided with meals on a
      fixed schedule. On a separate day, four subjects were fasted and then provided
      with an unexpected meal to clarify the effect of meal consumption on serum vaspin
      levels. Serum vaspin concentrations were determined by ELISA. RESULTS: Serum
      vaspin levels were highest in the early morning before breakfast and fell to
      trough levels within 2 h after breakfast. Serum vaspin levels also showed a
      preprandial rise and postprandial fall at lunch and dinner, although at lesser
      degrees than at breakfast. Intermeal vaspin concentrations reached a nadir in the
      mid-afternoon and showed a nocturnal rise, with peak nighttime vaspin levels
      being approximately 250% of nadir levels. Unscheduled food ingestion after a
      prolonged fast significantly reduced serum vaspin levels, suggesting that energy
      intake itself has a suppressive effect on serum vaspin levels. The diurnal
      pattern of serum vaspin concentrations was exactly reciprocal to that of insulin
      and of glucose. CONCLUSION: Serum vaspin levels have a meal-related diurnal
      variation, suggesting a role for vaspin in metabolic regulation. However, the
      reciprocal relationship between serum vaspin and insulin may negate the
      importance of vaspin as an physiological insulin sensitizer.

PMID- 20156924
TI  - Ecotypic variation of summer dormancy relaxation associated with rainfall
      gradient in the geophytic grass Poa bulbosa.
AB  - BACKGROUND AND AIMS: Summer dormancy is an adaptive trait in geophytes inhabiting
      regions with a Mediterranean climate, allowing their survival through the hot and
      dry summers. Summer dormancy in Poa bulbosa is induced by increasing day-length
      and temperature and decreasing water availability during spring. Populations from
      arid habitats became dormant earlier than those from mesic habitats. Relaxation
      of dormancy was promoted by the hot, dry summer conditions. Here we test the
      hypothesis that dormancy relaxation is also delayed in ecotypes of P. bulbosa
      inhabiting arid regions, as a cautious strategy related to the greater
      unpredictability of autumn rains associated with decreasing precipitation.
      METHODS: Ecotypes collected across a precipitation gradient (100-1200 mm year(
      1)) in the Mediterranean climate region were grown under similar conditions in a
      net-house in Israel. Differences among ecotypes in dormancy induction and
      dormancy relaxation were determined by measuring time to dormancy onset in
      spring, and time to sprouting after the first effective rain in autumn. Seasonal
      and ecotype variation in dormancy relaxation were assessed by measuring time to
      sprouting initiation, rate of sprouting and maximal sprouting of resting dry
      bulbs sampled in the net-house during late spring, and mid- and late summer, and
      planted in a wet substrate at temperatures promoting (10 degrees C) or limiting
      (20 degrees C) sprouting. KEY RESULTS: Earlier dormancy in the spring and delayed
      sprouting in autumn were correlated with decreasing mean annual rainfall at the
      site of ecotype origin. Seasonal and ecotype differences in dormancy relaxation
      were expressed in bulbs planted at 20 degrees C. During the summer, time to
      sprouting decreased while rate of sprouting and maximal sprouting increased,
      indicating dormancy relaxation. Ecotypes from more arid sites across the rainfall
      gradient showed delayed onset of sprouting and lower maximal sprouting, but did
      not differ in rate of sprouting. Planting at 10 degrees C promoted sprouting and
      cancelled differences among ecotypes in dormancy relaxation. CONCLUSIONS: Both
      the induction and the relaxation of summer dormancy in P. bulbosa are correlated
      with mean annual precipitation at the site of population origin. Ecotypes from
      arid habitats have earlier dormancy induction and delayed dormancy relaxation,
      compared with those from mesic habitats.

PMID- 20156925
TI  - Antidepressant discontinuation manic states: a critical review of the literature
      and suggested diagnostic criteria.
AB  - We critically appraised all published reports of hypomania and mania following
      antidepressant termination. To increase reliability and validity we devised
      diagnostic criteria for an antidepressant discontinuation or withdrawal 'manic
      state' based primarily on the Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition substance withdrawal criteria. A systematic literature
      review identified 24 reports meeting our criteria. Mean age was 39 years (range
      18-74), men and women were approximately equally represented, and more cases
      involved people with unipolar (n = 19) than bipolar disorder (n = 4). The median
      duration of preceding antidepressant treatment was 12 weeks (range 4 weeks-12
      years). All major antidepressant classes were involved (tricyclic antidepressants
      = 13; selective serotonin reuptake inhibitors = 5; monoamine oxidase inhibitors =
      3; selective serotonin-norepinephrine reuptake inhibitors = 2; miscellaneous =
      1). More cases followed abrupt antidepressant withdrawal (n = 11) than a tapered
      withdrawal (n = 6). Six cases appeared to meet the criteria of the Diagnostic and
      Statistical Manual of Mental Disorders, 4th edition for a manic episode, with two
      cases requiring inpatient admission. Of the 24 cases, nine resolved spontaneously
      without treatment (median duration = 25.5 days), six responded to antimanic
      drugs, four resolved following antidepressant reinstatement, and treatment was
      unclear in five cases. We conclude that antidepressant discontinuation
      hypomania/mania is a valid syndrome. It should be added to the differential
      diagnosis of hypomania/mania. The clinical implications and possible mechanisms
      are discussed.

PMID- 20156926
TI  - Preclinical and clinical pharmacology of TPA023B, a GABAA receptor
      &alpha;2/&alpha;3 subtype-selective partial agonist.
AB  - In the accompanying paper we describe how MRK-409 unexpectedly produced sedation
      in man at relatively low levels of GABA(A) receptor occupancy (~10%). Since it
      was not clear whether this sedation was mediated via the alpha2/alpha3 or alpha1
      GABA(A) subtype(s), we characterized the properties of TPA023B, a high-affinity
      imidazotriazine which, like MRK-409, has partial agonist efficacy at the alpha2
      and alpha3 subtype but is an antagonist at the alpha1 subtype, at which MRK-409
      has weak partial agonism. TPA023B gave dose- and time-dependent occupancy of rat
      brain GABA(A) receptors as measured using an in vivo [(3)H]flumazenil binding
      assay, with 50% occupancy corresponding to a respective dose and plasma drug
      concentration of 0.09 mg/kg and 19 ng/mL, the latter of which was similar to that
      observed in mice (25 ng/mL) and comparable to values obtained in baboon and man
      using [(11)C]flumazenil PET (10 and 5.8 ng/mL, respectively). TPA023B was
      anxiolytic in rodent and primate (squirrel monkey) models of anxiety (elevated
      plus maze, fear-potentiated startle, conditioned suppression of drinking,
      conditioned emotional response) yet had no significant effects in rodent or
      primate assays of ataxia and/or myorelaxation (rotarod, chain-pulling, lever
      pressing), up to doses (10 mg/kg) corresponding to occupancy of greater than 99%.
      In man, TPA023B was well tolerated at a dose (1.5 mg) that produced occupancy of
      >50%, suggesting that the sedation previously seen with MRK-409 is due to the
      partial agonist efficacy of that compound at the alpha1 subtype, and highlighting
      the importance of antagonist efficacy at this particular GABA(A) receptor
      population for avoiding sedation in man.

PMID- 20156927
TI  - A case of polymyositis associated with the presence of anti-proliferating cell
      nuclear antigen antibodies, a marker typically considered SLE specific.

PMID- 20156928
TI  - Calcinosis cutis and Sjogren's syndrome.
AB  - Cutaneous calcinosis can be classified into four types: dystrophic, metastatic,
      idiopathic and iatrogenic. Dystrophic calcification constitutes the most frequent
      variant and is associated with a large number of illnesses, among which are
      included some collagen diseases such as CREST syndrome, scleroderma,
      dermatomyositis and lupus erythematosus. We present a case of dystrophic
      calcinosis cutis, affecting the fingertip of a woman with a 10-year history of
      primary Sjogren's syndrome (SS). She has been receiving diltiazem as a treatment
      for the last 15 months, resulting in the partial resolution of the lesions. We
      emphasize the fact that the presence of calcinosis cutis has not been described
      previously in patients with SS, and that diltiazem has partially improved our
      patient's cutaneous lesions.

PMID- 20156929
TI  - Peripheral neuropathy in patients with primary antiphospholipid (Hughes')
      syndrome.
AB  - The involvement of the peripheral nervous system in diverse autoimmune diseases
      is well established. However, no appropriately designed studies have been
      performed in primary antiphospholipid syndrome (PAPS)-related peripheral
      neuropathy. We aimed to investigate the occurrence of peripheral neuropathy in
      patients diagnosed with PAPS. Twenty-six consecutive patients with PAPS (Sapporo
      criteria) and 20 age- and gender-matched healthy controls were enrolled at two
      referral centers. Exclusion criteria were secondary causes of peripheral
      neuropathy. A complete clinical neurologic exam followed by nerve conduction
      studies (NCS) was performed. Paresthesias were reported in eight patients (31%).
      Objective mild distal weakness and abnormal symmetric deep tendon reflexes were
      observed in three patients (11.5%). With regard to the electrophysiologic
      evidence of peripheral neuropathy, nine patients (35.0%) had alterations: four
      (15.5%) had pure sensory or sensorimotor distal axonal neuropathy (in two of them
      a carpal tunnel syndrome was also present) and one (4%) had sensorimotor
      demyelinating and axonal neuropathy involving upper and lower extremities, while
      four patients (15.5%) showed isolated carpal tunnel syndrome. Clinical and
      serologic results were similar in all the patients with PAPS, regardless of the
      presence of electrophysiologic alterations. In conclusion, peripheral neuropathy
      is a common asymptomatic abnormality in patients with PAPS. The routine
      performance of NCS may be considered when evaluating such patients.

PMID- 20156930
TI  - Mycophenolate: dual utility in rare conditions of HIV infection complicating
      lupus.

PMID- 20156931
TI  - Klinefelter syndrome with systemic lupus erythematosus in an Indian man.
AB  - Previously, cases of systemic lupus erythematosus (SLE) and Klinefelter syndrome
      (KS) in men have been reported in Western populations. We report the case of a 30
      year-old man from southern India with known infertility who was diagnosed to have
      SLE and KS by fluorescence in-situ hybridization, as routine karyotype cultures
      failed. The diagnosis has implications in management and highlights the need for
      strong clinical suspicion and laboratory confirmation of KS by molecular methods
      when suspected in all men with SLE. Quicker, long-term remission and genetic
      counseling of such individuals can help in better management and coping with this
      chronic, potentially fatal disease. Lupus (2010) 19, 870-871.

PMID- 20156933
TI  - The place of supportive, palliative and end-of-life care research in the United
      Kingdom Research Assessment Exercise, 2001 and 2008.
AB  - We report on a study of the place of research on supportive, palliative and end
      of-life care within the United Kingdom Research Assessment Exercise of 2001 and
      2008. Sixty-seven Higher Education Institutions in 2001 and 66 in 2008
      contributed work to the Research Assessment Exercise relevant to supportive,
      palliative and end-of-life care. This comprised 16 subject areas in 2001 and 25
      in 2008, and was generated by 178 authors in 2001 and 176 authors in 2008. Seven
      'high-intensity groups' of concentrated research activity were identified in
      2001, and eight such groups in 2008. Between the years little growth occurred in
      contributions to the Research Assessment Exercise relating to supportive,
      palliative and end-of-life care, and the 'high-intensity groups' remain
      relatively fragile. With one exception, there is no concentration of effort in
      clinical studies relating to the medical aspects of supportive, palliative and
      end-of-life care. By 2008 there were still less than 40 university academics in
      the UK with major commitments to research in supportive, palliative and end-of
      life care, as measured by their Research Assessment Exercise participation.

PMID- 20156932
TI  - Reduction in surface contamination with antineoplastic drugs in 22 hospital
      pharmacies in the US following implementation of a closed-system drug transfer
      device.
AB  - PURPOSE: Surface contamination with the antineoplastic drugs cyclophosphamide,
      ifosfamide, and 5-fluorouracil was compared in 22 US hospital pharmacies
      following preparation with standard drug preparation techniques or the PhaSeal(r)
      closed-system drug transfer device (CSTD). METHODS: Wipe samples were taken from
      biological safety cabinet (BSC) surfaces, BSC airfoils, floors in front of BSCs,
      and counters and analyzed for contamination with cyclophosphamide, ifosfamide,
      and 5-fluorouracil. Contamination was reassessed several months after the
      implementation of the CSTD. Surface contamination (ng/cm(2)) was compared between
      the two techniques and evaluated with the Signed Rank Test. RESULTS: Using the
      CSTD compared to the standard preparation techniques, a significant reduction in
      levels of contamination was observed for all drugs (cyclophosphamide: p < 0.0001;
      ifosfamide: p < 0.001; 5-fluorouracil: p < 0.01). Median values for surface
      contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil were reduced
      by 95%, 90%, and 65%, respectively. CONCLUSIONS: Use of the CSTD significantly
      reduces surface contamination when preparing cyclophosphamide, ifosfamide, and 5
      fluorouracil as compared to standard drug preparation techniques.

PMID- 20156934
TI  - Review: improving end-of-life care: a critical review of the gold standards
      framework in primary care.
AB  - The Gold Standards Framework aims to optimize primary palliative care for
      patients nearing the end of their lives. This paper critically reviews the impact
      of the Gold Standards Framework since its introduction in 2001 and indicates
      direction for further research and development. Literature was accessed using
      specific databases and by contacting subject area specialists. The resultant
      literature was appraised using an established framework to evaluate healthcare
      interventions. Fifteen documents were reviewed. The quality of evidence is
      constrained by methodological limitations, but consistently demonstrates that the
      Gold Standards Framework improves general practice processes, co-working and the
      quality of palliative care. However, implementation of the Gold Standards
      Framework is variable and the direct impact on patients and carers is not known.
      We conclude that the Gold Standards Framework has considerable potential to
      improve end-of-life care, but further work is needed to support uptake and
      consistency of implementation. Additional evidence about patient and carer
      outcomes will add to existing insights.

PMID- 20156935
TI  - Red cell distribution width in chronic heart failure: a new independent marker
      for prognosis?

PMID- 20156936
TI  - Should erythropoietin treatment in chronic heart failure be haemoglobin targeted?

PMID- 20156937
TI  - Assist devices in the new decade: from technical developments to political
      decisions.

PMID- 20156938
TI  - Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced
      by transforming growth factor-beta1 in cultured cardiac fibroblasts.
AB  - AIMS: Transforming growth factor-beta1 (TGF-beta1) and endoglin play a causal
      role in promoting cardiac fibrosis. Atorvastatin has been shown to have an
      inhibitory effect on cardiac fibroblasts in vitro. However, the effects of
      statins on TGF-beta1 and endoglin are poorly understood. We therefore sought to
      investigate the molecular mechanisms of atorvastatin on endoglin expression after
      TGF-beta1 stimulation in cardiac fibroblasts. METHODS AND RESULTS: Cultured
      cardiac fibroblasts were obtained from adult male Sprague-Dawley rat hearts. TGF
      beta1 stimulation increased endoglin and collagen I expression and atorvastatin
      inhibited the induction of endoglin and collagen I by TGF-beta1.
      Phosphatidylinositol-3 kinase (PI-3) and Akt inhibitors (wortmannin and Akt
      inhibitor X) completely attenuated the endoglin protein expression induced by TGF
      beta1. TGF-beta1 induced phosphorylation of PI-3 kinase and Akt, while
      atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of
      PI-3 kinase and Akt induced by TGF-beta1. The gel shift and promoter activity
      assay showed that TGF-beta1 increased Smad3/4-binding activity and endoglin
      promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4
      binding activity and endoglin promoter activity induced by TGF-beta1. TGF-beta1
      increased collagen I protein expression, while endoglin siRNA attenuated collagen
      I protein expression induced by TGF-beta1. Atorvastatin decreased left
      ventricular TGF-beta1, endoglin, and collagen I protein expression and fibrotic
      area in a rat model of volume overload heart failure. CONCLUSION: Atorvastatin
      inhibits endoglin expression through the inhibition of PI-3 kinase, Akt, and
      Smad3 phosphorylation, and reduced Smad3/4 binding activity and endoglin promoter
      activity in cardiac fibroblasts.

PMID- 20156939
TI  - Replacement and reactive myocardial fibrosis in idiopathic dilated
      cardiomyopathy: comparison of magnetic resonance imaging with right ventricular
      biopsy.

PMID- 20156940
TI  - Characteristics, outcomes, and predictors of mortality at 3 months and 1 year in
      patients hospitalized for acute heart failure.
AB  - AIMS: Acute heart failure (AHF) has a poor prognosis. We evaluated 3- and 12
      month mortality in different clinical classes of AHF patients from 30 European
      countries who were included in the EuroHeart Failure Survey (EHFS) II. METHODS
      AND RESULTS: Follow-up data were available for 2981 AHF patients, of these 62%
      had a history of chronic HF. One-year mortality after discharge was lower in
      patients with de novo AHF when compared with acutely decompensated chronic HF
      (ADCHF), 16.4 vs. 23.2% (P < 0.001). Cardiogenic shock conferred the highest
      cumulative 1-year mortality (52.9%) as a result of in-hospital mortality of
      39.3%. Long-term prognosis in decompensated AHF was also dismal. Hypertensive HF
      was associated with the lowest mortality (13.7% at 1 year). Age, prior myocardial
      infarction, creatinine level, and low plasma sodium were independently associated
      with mortality during the whole follow-up period. Diabetes, anaemia, and history
      of chronic HF were associated with worse and hypertension with better long-term
      survival. History of cerebrovascular disease was associated with worse short-term
      outcome. CONCLUSION: Early and late mortality differ between de novo AHF and
      ADCHF and between clinical classes of AHF. EHFS II identifies clinical risk
      markers and demonstrates the importance of a thorough characterization of AHF
      populations according to history and clinical presentation.

PMID- 20156941
TI  - Decreased likelihood of response to cardiac resynchronization in patients with
      severe heart failure.
AB  - AIMS: We hypothesized that a very advanced stage of dilated cardiomyopathy is
      associated with lower response to cardiac resynchronization therapy (CRT).
      METHODS AND RESULTS: A consecutive cohort of 147 patients was studied before
      device implantation and at 12 months follow-up. All patients were in NYHA
      functional class III-IV and had left-ventricular (LV) systolic dysfunction (LV
      ejection fraction 24 +/- 7%) and a wide QRS (171 +/- 29 ms). A patient who was
      alive without heart transplantation and had improved by at least 10% in the 6 min
      walking test at 12 months follow-up was considered a clinical responder. Fifty
      four patients (36%) did not respond to CRT (15 cardiac deaths, 4 heart
      transplantations). Quality of life indicators (>41 points), LV end-diastolic
      volumes (>200 mL) and mitral regurgitant orifice area (>16 mm(2)) at baseline
      were independent predictors of response to CRT. Patients were assigned 1 point
      for each predictive parameter. Patients with higher scores showed a significantly
      higher likelihood of non-response to CRT (chi(2) = 12 891, P = 0.005).
      CONCLUSION: The results show that non-responder patients have a more advanced
      stage of the disease, which suggests that CRT should be indicated earlier in the
      disease process.

PMID- 20156942
TI  - Extracorporeal membrane oxygenation as a rescue of intractable ventricular
      fibrillation and bridge to heart transplantation.
AB  - Extracorporeal membrane oxygenation (ECMO) systems have undergone rapid
      technological improvements and are now feasible options for medium-term support
      of severe cardiac or pulmonary failure. Intractable ventricular arrhythmia is a
      rare but well-established indication for heart transplantation. We report a case
      of persistent ventricular fibrillation (VF) that was rescued by insertion of
      peripheral veno-arterial ECMO during cardiopulmonary resuscitation, which
      provided support for 30 h of continuous VF and subsequently permitted urgent
      heart transplantation.

PMID- 20156943
TI  - Telephonic nurse case management for patients with diabetes and mental illnesses:
      a qualitative perspective.
AB  - OBJECTIVES: Gold Choice, a partially capitated Medicaid managed care programme
      for individuals with a behavioural health diagnosis, implemented a telephonic
      nurse case management (TNCM) programme to improve diabetes self-management. We
      sought to identify issues faced by patients with co-morbid behavioural health
      diagnoses and diabetes as documented in the telephonic nurse case manager's
      progress notes. We also explored the role of the TNCM in addressing members'
      needs. METHODS: We undertook a qualitative analysis of 853 de-identified progress
      notes from 539 Gold Choice members and conducted a semi-structured interview with
      the TNCM. RESULTS: Seven major themes emerged reflecting the nurse's perspectives
      on challenges faced by Gold Choice members and addressed by the TNCM: (1)
      Transience of the population. (2) Complex needs, involving not only medical and
      psychiatric conditions but also housing, transportation and survival. (3)
      Confusion regarding diabetes diagnosis. (4) Mistrust and suspicion. (5)
      Difficulties with medical care. (6) Need for diabetes self-management
      education/skills. (7) Marked appreciation that the TNCM would initiate contact
      and care about the patient. DISCUSSION: Members with co-morbid behavioural health
      diagnoses and diabetes constitute a complex population with extensive needs. The
      TNCM's role extends beyond diabetes care and entails social support as well as
      navigation of the healthcare and social service systems.

PMID- 20156944
TI  - Thrombin-cleaved osteopontin is increased in urine of patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To measure concentrations of the thrombin-cleaved isoform of
      osteopontin (OPN) in urine and plasma of patients with rheumatoid arthritis (RA),
      and to assess whether levels of thrombin-cleaved OPN are associated with measures
      of RA. METHODS: Subjects comprised 70 patients with RA, 20 patients with
      osteoarthritis (OA), and 46 healthy controls. RA disease activity was evaluated
      by tender joint count, swollen joint count, patient's global assessment of
      disease activity, erythrocyte sedimentation rate (ESR), and levels of C-reactive
      protein (CRP), matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF), as
      well as 28-joint count Disease Activity Score (DAS28). OPN levels in plasma and
      urine were measured by ELISA. RESULTS: Median levels of thrombin-cleaved OPN in
      urine (U-half) were significantly higher in RA patients (143.5 pmol/mmol Cr) than
      in healthy controls (67.9 pmol/mmol Cr) or OA patients (69.8 pmol/mmol Cr).
      Thrombin-cleaved OPN was not detected in plasma. U-half levels correlated
      significantly with levels of CRP (r = 0.26, p = 0.03), ESR (r = 0.26, p = 0.03),
      and RF (r = 0.28, p = 0.03). Median U-half levels were significantly higher in
      patients with stage III (249.9 pmol/mmol Cr) and IV (251.6 pmol/mmol Cr) disease
      than in patients with stage I (98.6 pmol/mmol Cr) disease. CONCLUSION: Our
      results suggest that urine levels of the thrombin-cleaved isoform of OPN may
      reflect the severity of active inflammatory arthritis in patients with RA.

PMID- 20156945
TI  - Elevated serum concentrations of triggering receptor expressed on myeloid cells-1
      in diffuse cutaneous systemic sclerosis: association with severity of pulmonary
      fibrosis.
AB  - OBJECTIVE: To determine serum concentrations and clinical association of soluble
      triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with
      systemic sclerosis (SSc). METHODS: Serum sTREM-1 levels from 17 patients with
      limited cutaneous SSc (lSSc), 24 patients with diffuse cutaneous SSc (dSSc), and
      29 healthy control individuals were examined by ELISA. RESULTS: Total SSc
      patients exhibited significantly elevated serum sTREM-1 levels relative to
      controls (p < 0.01). Serum sTREM-1 levels were significantly elevated in patients
      with dSSc compared to controls (p < 0.005) and lSSc patients (p < 0.05). By
      contrast, sTREM-1 levels in lSSc were similar to those in controls. Serum sTREM-1
      levels were significantly elevated in SSc patients with decreased percentage
      vital capacity (%VC). Consistent with this, serum sTREM-1 levels in SSc patients
      correlated negatively with %VC (r = -0.24, p < 0.005). Among SSc patients with
      pulmonary fibrosis, sTREM-1 levels were significantly increased in patients with
      decreased %VC or decreased percentage of diffusion capacity for carbon monoxide
      relative to those with normal values (p < 0.05). CONCLUSION: Serum sTREM-1 levels
      were elevated in dSSc patients and correlated with severity of pulmonary
      fibrosis, suggesting that serum sTREM-1 is a novel serological marker for the
      disease severity of SSc.

PMID- 20156946
TI  - Patient-derived joint counts are a potential alternative for determining Disease
      Activity Score.
AB  - OBJECTIVE: To investigate the correlation between the Disease Activity Score
      using a 28-joint count (DAS28) based on physician-derived joint counts and the
      DAS28 based on patient-derived joint counts (Pt-DAS28) in rheumatoid arthritis
      (RA). METHODS: Data from a multicenter, open-label study investigating the
      immunogenicity of etanercept (ETN) were analyzed. ETN-naive patients with active
      RA received ETN 50 mg once weekly alone or with methotrexate (MTX). Joint counts
      were performed at baseline, Week 12, and Week 24 by the physician and patient
      independently. Patients received instruction in performing joint assessments.
      RESULTS: Of 447 patients enrolled (ETN, n = 218; ETN + MTX, n = 229), most were
      women (79%) and the mean age was 54.5 years. Correlation coefficients between
      DAS28 and Pt-DAS28 were > or = 0.57 at baseline, Week 12, and Week 24. At Week
      24, 48%, 39%, and 12% of patients could be classified as having low, moderate, or
      high disease activity, respectively, using DAS28. Using Pt-DAS28, 43%, 39%, and
      18% were similarly classified. Agreement in the category of disease activity
      classification occurred in 72% of patients (kappa = 0.55). At Week 24, 78% of
      patients using DAS28 and 72% of patients using Pt-DAS28 were classified as
      moderate or good European League Against Rheumatism responders. CONCLUSION: These
      results support the possible use of patient-derived tender and swollen joint
      counts to aid in the assessment of disease activity and clinical response in
      patients with RA.

PMID- 20156947
TI  - Visual assessment of the spine bruckel instrument, a novel status tool to reflect
      appearance of the spine in patients with ankylosing spondylitis.
AB  - OBJECTIVE: The Visual Assessment of the Spine Bruckel Instrument (VASBI) is a new
      status tool developed by the Spondylitis Association of America and the
      University of Toronto to reflect spinal appearance in patients with ankylosing
      spondylitis (AS). Our objective was to validate the VASBI according to the
      Outcome Measures in Rheumatoid Arthritis Clinical Trials filter (truth,
      discrimination, and feasibility). METHODS: Three hundred patients with AS were
      asked to rate their degree of perceived spinal deformity using the VASBI. To
      evaluate construct validity, VASBI scores were compared with functional outcome,
      spinal mobility, and radiographic spinal damage. Test-retest reliability was
      evaluated using kappa statistic (kappa). RESULTS: Patient VASBI demonstrated
      strong correlation with spinal mobility (r = 0.543) and moderate correlation with
      functional impairment (r = 0.490) and structural damage (r = 0.309). Reliability
      for VASBI was very good (kappa = 0.973, p < 0.001). CONCLUSION: The VASBI is a
      novel tool with practical applications in a busy clinical setting as it
      simplifies assessment of AS spinal deformity. Our study demonstrates that the
      VASBI has good feasibility, construct validity, and reliability.

PMID- 20156948
TI  - Inflammation and microvascular and macrovascular endothelial dysfunction in
      rheumatoid arthritis: effect of treatment.
AB  - OBJECTIVE: To determine whether abnormalities in microvascular and macrovascular
      function in rheumatoid arthritis (RA) are associated with plasma markers [von
      Willebrand factor (VWF)] of endothelial dysfunction and inflammation [C-reactive
      protein (CRP)] and whether the abnormalities would be altered by treatment.
      Endothelial dysfunction and inflammation in RA may contribute to adverse
      cardiovascular events. Although endothelial dysfunction in RA has been
      demonstrated by altered plasma markers, the relationships with macrovascular and
      microvascular function are relatively unexplored. METHODS: We recruited 66
      patients with chronic RA, 48 community controls (CC), and 25 patients with
      diabetes and hypertension as a disease control group (DC). Subjects had venous
      blood sampled for plasma markers, and underwent laser Doppler perfusion imaging
      of forearm skin (to assess microvascular circulation) following acetylcholine and
      sodium nitroprusside iontophoresis, to assess endothelium-dependent and
      endothelium-independent responses, respectively. Brachial artery flow-mediated
      dilatation assessed endothelial dysfunction in a macrovascular bed. A subgroup of
      29 patients with RA were assessed pretherapy and after 2-4 weeks of antirheumatic
      therapy. RESULTS: As expected, patients with RA had higher CRP, erythrocyte
      sedimentation rate (ESR), and VWF. Endothelium-independent vasoreactivity was
      abnormal in RA, and this correlated negatively with CRP. All aspects of
      microvascular function were abnormal in the DC compared to the CC. Macrovascular
      function was preserved in RA but was abnormal in the DC group. Four weeks of
      antiinflammatory therapy reduced CRP and ESR but had no effect on any vascular
      function index in the patients with RA. CONCLUSION: Patients with RA have
      abnormal endothelium-independent microvascular function that correlates with
      inflammation but is not altered by short-term antiinflammatory therapy.

PMID- 20156950
TI  - Immunohistochemical analysis of osteoblasts in zygapophyseal joints of patients
      with ankylosing spondylitis reveal repair mechanisms similar to osteoarthritis.
AB  - OBJECTIVE: New bone formation of the spine is a typical feature of ankylosing
      spondylitis (AS). It is unknown whether new bone formation is part of a
      physiological repair process or a unique pathological entity of the disease.
      METHODS: We analyzed zygapophyseal joints from patients with AS and
      osteoarthritis (OA) undergoing spinal surgery for rigid hyperkyphosis (AS) or
      radiculopathy caused by severe OA. In 17 patients with AS, 11 with OA, and 5
      controls we performed immunohistochemical analysis of osteoprotegerin (OPG),
      nuclear factor-kappaB ligand (RANKL), and osteocalcin (OC) expression in
      osteoblasts and determined the trabecular thickness in AS and OA patients and
      controls. Osteoclasts were detected by tartrate-resistant alkaline phosphatase
      (TRAP) staining. RESULTS: Trabecular thickness was significantly lower in
      patients with AS compared to OA (p = 0.01). The absolute number of CD56+
      osteoblasts (p < 0.001) and OC+ (p = 0.002), OPG+ (p = 0.003), and RANKL+
      osteoblasts (p = 0.03) in AS patients was also significantly lower than in OA
      patients. The percentages of OC+, OPG+, and RANKL+ osteoblasts did not differ
      between AS and OA (p > 0.05 in all cases). In controls, the percentages of OPG+
      (p = 0.013) and OC+ (p = 0.034) but not RANKL+ (p > 0.05) osteoblasts were
      significantly lower compared to AS patients. The frequency of TRAP+ osteoclasts
      in AS patients was significantly lower compared to OA (p < 0.001), but higher
      compared to controls. CONCLUSION: Immunohistochemical analysis of zygapophyseal
      joints suggested that osteoblast activity is similar in AS and OA, indicating
      that new bone formation is possibly a physiological function of repair in both
      diseases.

PMID- 20156949
TI  - A European multicenter randomized double-blind placebo-controlled monotherapy
      clinical trial of milnacipran in treatment of fibromyalgia.
AB  - OBJECTIVE: This randomized, double-blind, placebo-controlled, multicenter study
      investigated the efficacy and safety of milnacipran in the treatment of
      fibromyalgia (FM) in a European population. METHODS: Outpatients diagnosed with
      FM according to 1990 American College of Rheumatology criteria (N = 884) were
      randomized to placebo (n = 449) or milnacipran 200 mg/day (n = 435) for 17 weeks
      (4-week dose escalation, 12-week stable dose, 9-day down-titration), followed by
      a 2-week posttreatment period. The primary efficacy criterion was a 2-measure
      composite responder analysis requiring patients to achieve simultaneous
      improvements in pain (>or= 30% improvement from baseline in visual analog scale,
      24-hour morning recall) and a rating of "very much" or "much" improved on the
      Patient Global Impression of Change scale. If responder analysis was positive,
      Fibromyalgia Impact Questionnaire (FIQ) was included as an additional key primary
      efficacy measure. RESULTS: At the end of the stable dose period (Week 16),
      milnacipran 200 mg/day showed significant improvements from baseline relative to
      placebo in the 2-measure composite responder criteria (p = 0.0003) and FIQ total
      score (p = 0.015). Significant improvements were also observed in multiple
      secondary efficacy endpoints, including Short-Form 36 Health Survey (SF-36)
      Physical Component Summary (p = 0.025), SF-36 Mental Component Summary (p =
      0.007), Multidimensional Fatigue Inventory (p = 0.006), and Multiple Ability Self
      Report Questionnaire (p = 0.041). Milnacipran was safe and well tolerated;
      nausea, hyperhidrosis, and headache were the most common adverse events.
      CONCLUSION: Milnacipran is an effective and safe treatment for pain and other
      predominant symptoms of FM. Registered as trial no. NCT00436033.

PMID- 20156951
TI  - Associations of occupational tasks with knee and hip osteoarthritis: the Johnston
      County Osteoarthritis Project.
AB  - OBJECTIVE: This cross-sectional study examined associations of occupational tasks
      with radiographic and symptomatic osteoarthritis (OA) in a community-based
      sample. METHODS: Participants from the Johnston County Osteoarthritis Project (n
      = 2729) self-reported the frequency of performing 10 specific occupational tasks
      at the longest job ever held (never/seldom/sometimes vs often/always) and
      lifetime exposure to jobs that required spending > 50% of their time doing 5
      specific tasks or lifting 22, 44, or 110 pounds 10 times weekly. Multivariable
      logistic regression models examined associations of each occupational task
      separately with radiographic and symptomatic knee and hip OA, controlling for
      age, race, gender, body mass index, prior knee or hip injury, and smoking.
      RESULTS: Radiographic hip and knee OA were not significantly associated with any
      occupational tasks, but several occupational tasks were associated with increased
      odds of both symptomatic knee and hip OA: lifting > 10 pounds, crawling, and
      doing heavy work while standing (OR 1.4-2.1). More occupational walking and
      standing and less sitting were also associated with symptomatic knee OA, and more
      bending/twisting/reaching was associated with symptomatic hip OA. Exposure to a
      greater number of physically demanding occupational tasks at the longest job was
      associated with greater odds of both symptomatic knee and hip OA. CONCLUSION: Our
      results confirm an association of physically demanding occupational tasks with
      both symptomatic knee and hip OA, including several specific activities that
      increased the odds of OA in both joint groups. These tasks represent
      possibilities for identifying and targeting at-risk individuals with preventive
      interventions.

PMID- 20156952
TI  - Psychological correlates of self-reported disease activity in ankylosing
      spondylitis.
AB  - OBJECTIVE: To investigate the role of psychological variables in self-reported
      disease activity in patients with ankylosing spondylitis (AS), while controlling
      for demographic and medical variables. METHODS: Patients with AS (n = 294)
      meeting modified New York criteria completed psychological measures evaluating
      depression, resilience, active and passive coping, internality, and helplessness.
      Demographic, clinical, and radiologic data were also collected. Univariate and
      multivariate analyses were completed to determine the strength of the correlation
      of psychological variables with disease activity, as measured by the Bath AS
      Disease Activity Index (BASDAI). RESULTS: In the multivariate regression
      analysis, the psychological variables contributed significantly to the variance
      in BASDAI scores, adding an additional 33% to the overall R-square beyond that
      accounted for by demographic and medical variables (combined R-square 18%).
      Specifically, arthritis helplessness and depression accounted for the most
      significant portion of the variance in BASDAI scores in the final model.
      CONCLUSION: Arthritis helplessness and depression accounted for significant
      variability in self-reported disease activity beyond clinical and demographic
      variables in patients with AS. These findings have important clinical
      implications in the treatment and monitoring of disease activity in AS, and
      suggest potential avenues of intervention.

PMID- 20156953
TI  - Standardization of joint examination technique leads to a significant decrease in
      variability among different examiners.
AB  - OBJECTIVE: To reduce the amount of variability among assessors, we conducted
      joint examination standardization seminars in conjunction with multicenter
      clinical trials for patients with rheumatoid arthritis (RA). The examination
      techniques used were based on the recommendations of the European League Against
      Rheumatism (EULAR). METHODS: To evaluate the effect of standardization,
      participants at the seminars examined a given patient with RA before and after
      they were made familiar with the EULAR examination technique. The number of
      tender and swollen joints as well as the variance among the examiners before and
      after the training were compared. Joints were rated positive or negative for
      tenderness and swelling without grading. RESULTS: Overall, 553 individuals from a
      variety of countries in Europe, North America, Asia, and Australia participated.
      Examiners included different kinds of health professionals, mainly physicians and
      nurses. We found a substantial variance among examiners before the training in
      the standardized method. This variance could be significantly reduced by the
      training. We also found that the number of joints considered active was markedly
      reduced after the training. CONCLUSION: Standardized joint examination training
      significantly reduces variability among different assessors.

PMID- 20156954
TI  - Summarizing historical information on controls in clinical trials.
AB  - BACKGROUND: Historical information is always relevant when designing clinical
      trials, but it might also be incorporated in the analysis. It seems appropriate
      to exploit past information on comparable control groups. PURPOSE: Phase IV and
      proof-of-concept trials are used to discuss aspects of summarizing historical
      control data as prior information in a new trial. The importance of a fair
      assessment of the similarity of control parameters is emphasized. METHODS: The
      methodology is meta-analytic-predictive. Heterogeneity of control parameters is
      expressed via the between-trial variation, which is the key parameter determining
      the prior effective sample size and its upper bound (prior maximum sample size).
      RESULTS: For a Phase IV trial (930 control patients in 11 historical trials)
      between-trial heterogeneity was fairly small, resulting in a prior effective
      sample size of approximately 90 patients. For a proof-of-concept trial (363
      patients in four historical trials) heterogeneity was moderate to substantial,
      resulting in a prior effective sample size of approximately 20. For another proof
      of-concept trial (14 patients in one historical trial), assuming substantial
      heterogeneity implied a prior effective sample size of 7. The prior effective
      sample size can only be large if the amount of historical data is large and
      between-trial heterogeneity is small. The prior effective sample size is bounded
      by the prior maximum sample size (ratio of within- to between-trial variance),
      irrespective of the amount of historical data. LIMITATIONS: The meta-analytic
      predictive approach assumes exchangeability of control parameters across trials.
      Due to the difficulty to quantify between-trial variability, sensitivity of
      conclusions regarding assumptions and type of inference should be assessed.
      CONCLUSIONS: The use of historical control information is a valuable option and
      may lead to more efficient clinical trials. The proposed approach is attractive
      for nonconfirmatory trials, but under certain circumstances extensions to the
      confirmatory setting could be envisaged as well.

PMID- 20156955
TI  - Methodological issues in the use of composite endpoints in clinical trials:
      examples from the HIV field.
AB  - BACKGROUND: In many fields, the choice of a primary endpoint for a trial is not
      always the ultimate clinical endpoint of interest, but rather some surrogate
      endpoint believed to be relevant for predicting the effect of the intervention on
      the clinical endpoint. The classic example of such a field is clinical HIV
      treatment research, where a variety of primary endpoints are used to evaluate the
      efficacy of new antiretroviral drugs or new combinations of existing drugs. The
      choice of endpoint reflects either the goal of therapy as recommended by
      treatment guidelines (e.g. rapid virological suppression) or the licensing
      requirements of official drug approval organizations (e.g. time to loss of
      virological response [TLOVR]). PURPOSE: To review the diversity of endpoints used
      in recent clinical trials in HIV infection and highlight the methodological
      issues. METHODS: We identified articles relating to antiretroviral therapy by
      searching PubMed and through hand searches of relevant conference abstracts. We
      restricted the search to randomized controlled trials conducted in HIV-infected
      adults published/presented from January 2005 until March 2008. RESULTS: We
      identified 28 trials in antiretroviral-naive patients (i.e. patients who were
      starting antiretroviral therapy for the first time at the time of randomization)
      and 23 trials in antiretroviral-experienced patients. Most trials were performed
      for purposes of drug licensing, but others were focused on strategies of using
      approved drugs. Most trials (40 of 51) used a composite primary endpoint (TLOVR
      in 13). Of note, 22 of these 40 studies reported that they had used a purely
      virological efficacy endpoint, but the primary endpoint was actually a composite
      one due to the way in which missing data and treatment switches were considered
      as failures. LIMITATIONS: Examples are restricted to HIV clinical trials.
      CONCLUSIONS: Whilst most current HIV clinical trials use composite primary
      endpoints, there are substantial differences in the components that make up these
      endpoints. In HIV and other fields where precise definitions are variable,
      guidelines for standardization of definition and reporting would greatly improve
      the ability to compare trial results.

PMID- 20156956
TI  - A simulation study evaluating approaches to the analysis of ordinal outcome data
      in randomized controlled trials in traumatic brain injury: results from the
      IMPACT Project.
AB  - BACKGROUND: Clinical trials in traumatic brain injury have a disappointing track
      record, with a long history of 'negative' Phase III trials. One contributor to
      this lack of success is almost certainly the low efficiency of the conventional
      approach to the analysis, which discards information by dichotomizing an ordinal
      outcome scale. PURPOSE: Our goal was to evaluate the potential efficiency gains,
      which can be achieved by using techniques, which extract additional information
      from ordinal outcome data - the proportional odds model and the sliding
      dichotomy. In addition, we evaluated the additional efficiency gains, which can
      be achieved through covariate adjustment. METHODS: The study was based on
      simulations, which were built around a database of patient-level data extracted
      from eight Phase III trials and three observational studies in traumatic brain
      injury. Two different putative treatment effects were explored, one which
      followed the proportional odds model, and the other which assumed that the effect
      of the intervention was to reduce the risk of death without changing the
      distribution of outcomes within survivors. The results are expressed as
      efficiency gains, reported as the percentage reduction in sample size that can be
      used with the ordinal analyses without loss of statistical power relative to the
      conventional binary analysis. RESULTS: The simulation results show substantial
      efficiency gains. Use of the sliding dichotomy allows sample sizes to be reduced
      by up to 40% without loss of statistical power. The proportional odds model gives
      modest additional gains over and above the gains achieved by use of the sliding
      dichotomy. LIMITATIONS: As with any simulation study, it is difficult to know how
      far the findings may be extrapolated beyond the actual situations that were
      modeled. CONCLUSIONS: Both ordinal techniques offer substantial efficiency gains
      relative to the conventional binary analysis. The choice between the two
      techniques involves subtle value judgments. In the situations examined, the
      proportional odds model gave efficiency gains over and above the sliding
      dichotomy, but arguably, the sliding dichotomy is more intuitive and clinically
      appealing.

PMID- 20156957
TI  - Principles for defining adverse events in behavioral intervention research:
      lessons from a family-focused adolescent drug abuse trial.
AB  - BACKGROUND: Behavioral intervention research has lagged behind biomedical
      research in developing principles for defining, categorizing, identifying,
      reporting, and monitoring adverse events and unanticipated problems. PURPOSE: In
      this article we present a set of principles for defining adverse events and how
      they were applied in a large national multi-site family therapy study for
      substance-using adolescents, The Brief Strategic Family Therapy (BSFT)
      Effectiveness Study. METHODS: The BSFT Effectiveness study tested how BSFT
      compares to Treatment as Usual (TAU) for the treatment of drug-abusing
      adolescents. During protocol development, experts in the BSFT intervention,
      medical safety officers, ethicists and senior investigators defined the
      procedures for identifying, tracking and reporting adverse events for drug using
      adolescents as well as their family members. During this process the team
      identified five key guiding principles. RESULTS: The five guiding principles that
      were used for defining adverse events in this behavioral trial were that that the
      adverse events should be validated and plausible, and that monitoring systems
      should assess relatedness, be systematic, and are a shared responsibility. The
      following non-serious adverse events were identified: arrest, school suspension
      and drop out, runaway, kicked out of home and violence. The serious adverse
      events in this study for the identified adolescent participant and all other
      consented family members were physical or sexual abuse, suicidal behavior,
      homicidal behavior, hospitalization (drug related or psychiatric related only)
      and death. The methods used in categorizing, identifying and reporting adverse
      events in the BSFT trial are outlined. More than 50% of the adolescent population
      (277/481 = 57.5 %) experienced an adverse event during the trial. Family members
      experienced less adverse events, (61/1338 = 4.5%). The most common event for the
      adolescent group was arrest (164/277= 59.2%), followed by school
      suspension/dropout (143/277 = 51.6%), and runaway (79/277= 28.5 %). For the
      family member group, the most common event was violence (25/ 61 = 40.9%) followed
      by arrest (13/61 = 21.3%). There was a significant difference in the presence of
      adverse events in family members that were randomized to BSFT 44/721 (6.1%) when
      compared to Treatment as Usual 17/617 (2.8%) (p = 0.004). A probable explanation
      for this is that there were more opportunities to identify adverse events for
      family members assigned to BSFT because family members attended therapy sessions.
      This difference may also represent the risk for family members that participate
      in an evidence-based family intervention like BSFT. LIMITATIONS: The utility of
      the principles outside of the BSFT trial is unknown. CONCLUSIONS: Based on the
      events reported in this trial, the efforts for monitoring and categorizing
      adverse events appeared justified and appropriate. The strategies and principles
      described in this paper may be useful for those developing safety plans for
      behavioral intervention research, and to family therapy researchers for assessing
      the safety of behavioral family interventions.

PMID- 20156958
TI  - Does the source of death information affect cancer screening efficacy results? A
      study of the use of mortality review versus death certificates in four randomized
      trials.
AB  - BACKGROUND: Often in randomized controlled trials of cancer screening, cause of
      death is determined by a mortality review committee. However, little is known
      regarding how findings from mortality review compare to those from death
      certificates alone. PURPOSE: To examine the results of four different U. S.
      trials of cancer screening when death certificate data only were used, as
      compared to results using all available mortality review information. METHODS:
      Trials included were the Health Insurance Plan of New York breast screening trial
      (HIP), the Minnesota trial of fecal occult blood testing, and the Johns Hopkins
      and Mayo Lung Projects, which each examined chest x-ray and sputum cytology. The
      sensitivity, specificity, positive and negative predictive values, and Cohen's
      kappa for death certificates were calculated for all arms of all trials. Separate
      intention-to-screen analyses were conducted for each trial using cause of death
      information from either death certificates alone or full mortality review data.
      RESULTS: Generally there was excellent agreement between the death certificates
      and the mortality review committee as to the underlying cause of death (kappa
      >0.85 in all cases); death certificate agreement was similar between arms in all
      trials. Modest changes in the screening effectiveness estimates were observed
      when mortality review information was utilized, ranging from a 9% decrease to a
      2% increase in the calculated mortality rate ratios. However, in one instance
      (HIP) a statistically significant benefit of screening was observed when
      mortality review committee data were used (rate ratio (RR) 0.77, 95% confidence
      interval (CI) 0.62- 0.95) but not when death certificate data were used (RR 0.82,
      95% CI 0.65-1.03). LIMITATIONS: Although considered to be the gold standard, even
      carefully conducted mortality review may result in errors in cause of death
      assignment. CONCLUSIONS: For each trial, results were similar regardless of the
      source of cause of death information.

PMID- 20156959
TI  - Failsafe automation of Phase II clinical trial interim monitoring for stopping
      rules.
AB  - BACKGROUND: In Phase II clinical trials in cancer, preventing the treatment of
      patients on a study when current data demonstrate that the treatment is
      insufficiently active or too toxic has obvious benefits, both in protecting
      patients and in reducing sponsor costs. Considerable efforts have gone into
      experimental designs for Phase II clinical trials with flexible sample size,
      usually implemented by early stopping rules. The intended benefits will not
      ensue, however, if the design is not followed. Despite the best intentions,
      failures can occur for many reasons. PURPOSE: The main goal is to develop an
      automated system for interim monitoring, as a backup system supplementing the
      protocol team, to ensure that patients are protected. A secondary goal is to
      stimulate timely recording of patient assessments. METHODS: We developed key
      concepts and performance needs, then designed, implemented, and deployed a
      software solution embedded in the clinical trials database system. RESULTS: The
      system has been in place since October 2007. One clinical trial tripped the
      automated monitor, resulting in e-mails that initiated statistician/investigator
      review in timely fashion. LIMITATIONS: Several essential contributing activities
      still require human intervention, institutional policy decisions, and
      institutional commitment of resources. CONCLUSIONS: We believe that implementing
      the concepts presented here will provide greater assurance that interim
      monitoring plans are followed and that patients are protected from inadequate
      response or excessive toxicity. This approach may also facilitate wider
      acceptance and quicker implementation of new interim monitoring algorithms.

PMID- 20156960
TI  - Impact of supplemental site grants to increase African American accrual for the
      Selenium and Vitamin E Cancer Prevention Trial.
AB  - BACKGROUND: African American accrual to prevention trials at rates representative
      of the disease burden experienced by this population requires additional
      resources and focused efforts. PURPOSE: To describe the rationale, context, and
      criteria for selection of sites that received Minority Recruitment Enhancement
      Grants (MREGs) to increase African American recruitment to the Selenium and
      Vitamin E Cancer Prevention Trial (SELECT). To determine if African American
      accrual was higher among the 15 MREG sites when compared with similar nonawarded
      sites. METHODS: Changes in African American accrual at sites that received MREGs
      are compared with changes in a group of 15, frequency-matched, nonawarded sites
      using a quasi-experimental, post hoc analysis. Successful and unsuccessful
      recruitment strategies reported by the MREG sites are described. RESULTS: The
      increased number of African American participants accrued per month at MREG sites
      post-funding was higher than the change at comparison sites by a factor of 3.38
      (p = 0.004, 95% CI: 1.51-7.57). An estimated 602 additional African American
      participants were recruited at MREG sites due to MREG funding, contributing to
      the overall 14.9% African American recruitment. Successful recruitment strategies
      most reported by MREG sites included increasing staff, transportation resources,
      recruiting through the media, mailings, and prostate cancer screening clinics
      during off-hours. LIMITATIONS: Comparison sites were chosen retrospectively, not
      by randomization. Although comparison sites were selected to be similar to MREG
      sites with regard to potential confounding factors, it is possible that unknown
      factors could have biased results. Cost-effective analyses were not conducted.
      CONCLUSIONS: MREG sites increased African American accrual in the post-funding
      period more than comparison sites, indicating MREG funding enhanced the sites'
      abilities to accrue African American participants. Targeted grants early in the
      accrual period may be a useful multi-site intervention to increase African
      American accrual for a prevention study where adequate African American
      representation is essential.

PMID- 20156962
TI  - Unconventional secretion of Pichia pastoris Acb1 is dependent on GRASP protein,
      peroxisomal functions, and autophagosome formation.
AB  - In contrast to the enormous advances made regarding mechanisms of conventional
      protein secretion, mechanistic insights into the unconventional secretion of
      proteins are lacking. Acyl coenzyme A (CoA)-binding protein (ACBP; AcbA in
      Dictyostelium discoideum), an unconventionally secreted protein, is dependent on
      Golgi reassembly and stacking protein (GRASP) for its secretion. We discovered,
      surprisingly, that the secretion, processing, and function of an AcbA-derived
      peptide, SDF-2, are conserved between the yeast Pichia pastoris and D.
      discoideum. We show that in yeast, the secretion of SDF-2-like activity is GRASP
      dependent, triggered by nitrogen starvation, and requires autophagy proteins as
      well as medium-chain fatty acyl CoA generated by peroxisomes. Additionally, a
      phospholipase D implicated in soluble N-ethyl-maleimide sensitive fusion protein
      attachment protein receptor-mediated vesicle fusion at the plasma membrane is
      necessary, but neither peroxisome turnover nor fusion between autophagosomes and
      the vacuole is essential. Moreover, yeast Acb1 and several proteins required for
      its secretion are necessary for sporulation in P. pastoris. Our findings
      implicate currently unknown, evolutionarily conserved pathways in unconventional
      secretion.

PMID- 20156963
TI  - Plakophilin 1 stimulates translation by promoting eIF4A1 activity.
AB  - Plakophilins 1-3 (PKP1-3) are desmosomal proteins of the p120(ctn) family of
      armadillo-related proteins that are essential for organizing the desmosomal
      plaque. Recent findings identified PKPs in stress granules, suggesting an
      association with the translational machinery. However, a role of PKPs in
      controlling translation remained elusive so far. In this study, we show a direct
      association of PKP1 with the eukaryotic translation initiation factor 4A1
      (eIF4A1). PKP1 stimulated eIF4A1-dependent translation via messenger RNA cap and
      encephalomyocarditis virus internal ribosomal entry site (IRES) structures,
      whereas eIF4A1-independent translation via hepatitis C virus IRES was not
      affected. PKP1 copurified with eIF4A1 in the cap complex, and its overexpression
      stimulated eIF4A1 recruitment into cap-binding complexes. At the molecular level,
      PKP1 directly promoted eIF4A1 adenosine triphosphatase activity. The stimulation
      of translation upon PKP1 overexpression correlated with the up-regulation of
      proliferation and cell size. In conclusion, these findings identify PKP1 as a
      regulator of translation and proliferation via modulation of eIF4A1 activity and
      suggest that PKP1 controls cell growth in physiological and pathological
      conditions.

PMID- 20156965
TI  - Signal sequence insufficiency contributes to neurodegeneration caused by
      transmembrane prion protein.
AB  - Protein translocation into the endoplasmic reticulum is mediated by signal
      sequences that vary widely in primary structure. In vitro studies suggest that
      such signal sequence variations may correspond to subtly different functional
      properties. Whether comparable functional differences exist in vivo and are of
      sufficient magnitude to impact organism physiology is unknown. Here, we
      investigate this issue by analyzing in transgenic mice the impact of signal
      sequence efficiency for mammalian prion protein (PrP). We find that replacement
      of the average efficiency signal sequence of PrP with more efficient signals
      rescues mice from neurodegeneration caused by otherwise pathogenic PrP mutants in
      a downstream hydrophobic domain (HD). This effect is explained by the
      demonstration that efficient signal sequence function precludes generation of a
      cytosolically exposed, disease-causing transmembrane form of PrP mediated by the
      HD mutants. Thus, signal sequences are functionally nonequivalent in vivo, with
      intrinsic inefficiency of the native PrP signal being required for pathogenesis
      of a subset of disease-causing PrP mutations.

PMID- 20156964
TI  - Amiloride inhibits macropinocytosis by lowering submembranous pH and preventing
      Rac1 and Cdc42 signaling.
AB  - Macropinocytosis is differentiated from other types of endocytosis by its unique
      susceptibility to inhibitors of Na(+)/H(+) exchange. Yet, the functional
      relationship between Na(+)/H(+) exchange and macropinosome formation remains
      obscure. In A431 cells, stimulation by EGF simultaneously activated
      macropinocytosis and Na(+)/H(+) exchange, elevating cytosolic pH and stimulating
      Na(+) influx. Remarkably, although inhibition of Na(+)/H(+) exchange by amiloride
      or HOE-694 obliterated macropinocytosis, neither cytosolic alkalinization nor
      Na(+) influx were required. Instead, using novel probes of submembranous pH, we
      detected the accumulation of metabolically generated acid at sites of
      macropinocytosis, an effect counteracted by Na(+)/H(+) exchange and greatly
      magnified when amiloride or HOE-694 were present. The acidification observed in
      the presence of the inhibitors did not alter receptor engagement or
      phosphorylation, nor did it significantly depress phosphatidylinositol-3-kinase
      stimulation. However, activation of the GTPases that promote actin remodelling
      was found to be exquisitely sensitive to the submembranous pH. This sensitivity
      confers to macropinocytosis its unique susceptibility to inhibitors of Na(+)/H(+)
      exchange.

PMID- 20156966
TI  - BAG1 restores formation of functional DJ-1 L166P dimers and DJ-1 chaperone
      activity.
AB  - Mutations in the gene coding for DJ-1 protein lead to early-onset recessive forms
      of Parkinson's disease. It is believed that loss of DJ-1 function is causative
      for disease, although the function of DJ-1 still remains a matter of controversy.
      We show that DJ-1 is localized in the cytosol and is associated with membranes
      and organelles in the form of homodimers. The disease-related mutation L166P
      shifts its subcellular distribution to the nucleus and decreases its ability to
      dimerize, impairing cell survival. Using an intracellular foldase biosensor, we
      found that wild-type DJ-1 possesses chaperone activity, which is abolished by the
      L166P mutation. We observed that this aberrant phenotype can be reversed by the
      expression of the cochaperone BAG1 (Bcl-2-associated athanogene 1), restoring DJ
      1 subcellular distribution, dimer formation, and chaperone activity and
      ameliorating cell survival.

PMID- 20156967
TI  - Unconventional secretion of Acb1 is mediated by autophagosomes.
AB  - Starving Dictyostelium discoideum cells secrete AcbA, an acyl coenzyme A-binding
      protein (ACBP) that lacks a conventional signal sequence for entering the
      endoplasmic reticulum (ER). Secretion of AcbA in D. discoideum requires the Golgi
      associated protein GRASP. In this study, we report that starvation-induced
      secretion of Acb1, the Saccharomyces cerevisiae ACBP orthologue, also requires
      GRASP (Grh1). This highlights the conserved function of GRASP in unconventional
      secretion. Although genes required for ER to Golgi or Golgi to cell surface
      transport are not required for Acb1 secretion in yeast, this process involves
      autophagy genes and the plasma membrane t-SNARE, Sso1. Inhibiting transport to
      vacuoles does not affect Acb1 secretion. In sum, our experiments reveal a unique
      secretory pathway where autophagosomes containing Acb1 evade fusion with the
      vacuole to prevent cargo degradation. We propose that these autophagosome
      intermediates fuse with recycling endosomes instead to form multivesicular body
      carriers that then fuse with the plasma membrane to release cargo.

PMID- 20156968
TI  - Unconventional secretion by autophagosome exocytosis.
AB  - In this issue, Duran et al. (2010. J. Cell Biol. doi: 10.1083/jcb.200911154) and
      Manjithaya et al. (2010. J. Cell Biol. doi: 10.1083/jcb.200911149) use yeast
      genetics to reveal a role for autophagosome intermediates in the unconventional
      secretion of an acyl coenzyme A (CoA)-binding protein that lacks an endoplasmic
      reticulum signal sequence. Medium-chain acyl CoAs are also required and may be
      important for substrate routing to this pathway.

PMID- 20156969
TI  - Immunohistochemical identification of the PTHR1 parathyroid hormone receptor in
      normal and neoplastic human tissues.
AB  - BACKGROUND: Parathyroid hormone (PTH) is a crucial regulator of calcium
      homoeostasis in humans. Although it is well known that PTH acts primarily on
      kidney and bone, the precise cellular and subcellular sites of PTH action have
      not been visualised in human tissues. METHOD: We developed and characterised a
      novel anti-peptide antibody to the carboxy-terminal region of the human PTH
      receptor type 1 (PTHR1). Specificity of the antiserum was demonstrated by i)
      detection of a broad band migrating at M(r) 85,000-95,000 in western blots of
      membranes from human kidney and PTHR1-transfected cells; ii) cell surface
      staining of PTHR1-transfected cells; iii) translocation of PTHR1 receptor
      immunostaining after agonist exposure; and iv) abolition of tissue immunostaining
      by preadsorption of the antibody with its immunising peptide. The distribution of
      PTHR1 receptors was investigated in 320 human tumours and their tissues of
      origin. RESULTS: In the kidney, PTHR1 receptors were predominantly detected at
      the basolateral plasma membrane of epithelial cells in the proximal and distal
      tubules but not in the thin limbs of Henle, collecting ducts or glomeruli. In
      bone, PTHR1 receptors were detected as discrete plasma membrane staining of
      osteocytes and osteoblasts, whereas osteoclasts remained unstained. In addition,
      PTHR1 was found in the gut and in a number of neoplastic tissues including
      colorectal carcinoma, prostate cancer, renal cell carcinoma and osteosarcoma.
      CONCLUSION: This is the first localisation of PTHR1 receptors in human tissues at
      the cellular level. The overexpression of PTHR1 receptors may provide a molecular
      basis for efficient targeting of human tumours with radiolabelled PTH analogues.

PMID- 20156970
TI  - Complete disappearance of a GH-secreting pituitary macroadenoma in a patient with
      acromegaly: effect of treatment with lanreotide Autogel and consequence of
      treatment withdrawal.
AB  - BACKGROUND: Somatostatin analogs (SA) are the cornerstone in the medical
      treatment of acromegaly, used as either primary or adjunctive therapy. In
      particular, SA are effective in inducing the biochemical remission of the disease
      and tumor shrinkage, although only few cases of complete disappearance of the
      pituitary tumor in patients treated with SA as long-acting formulations have been
      reported. SA withdrawal has been demonstrated to keep safe levels of GH and IGF1
      at least in a small subset of patients well responsive to SA, although it is
      generally followed by disease recurrence after several months. CASE REPORT: A 61
      year-old female patient bearing a very large GH-secreting pituitary macroadenoma
      was treated with 12-month lanreotide Autogel (ATG), at the initial dose of 120
      mg/28 days. After 3 months, GH and IGF1 levels were fully normalized, to prolong
      the administration interval from 28 to 56 days. After 6 months of treatment, a
      significant tumor shrinkage (90% of baseline size) was observed, whereas GH and
      IGF1 excess was still well controlled. After 12-month therapy, a complete
      disappearance of the pituitary tumor was observed, and the hormonal evaluation
      confirmed the complete biochemical remission of acromegaly. Lanreotide ATG
      treatment was withdrawn. The clinical, biochemical, and radiological remission of
      acromegaly was maintained 24 months after lanreotide ATG treatment
      discontinuation, without evidence of disease recurrence. CONCLUSIONS: This report
      represents an exemplary case of the potentiality of treatment with lanreotide ATG
      in inducing a complete remission of acromegalic disease, persistent after a long
      period of time from treatment withdrawal.

PMID- 20156971
TI  - Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large
      established melanoma after transfer into lymphopenic hosts.
AB  - Adoptive transfer of large numbers of tumor-reactive CD8(+) cytotoxic T
      lymphocytes (CTLs) expanded and differentiated in vitro has shown promising
      clinical activity against cancer. However, such protocols are complicated by
      extensive ex vivo manipulations of tumor-reactive cells and have largely focused
      on CD8(+) CTLs, with much less emphasis on the role and contribution of CD4(+) T
      cells. Using a mouse model of advanced melanoma, we found that transfer of small
      numbers of naive tumor-reactive CD4(+) T cells into lymphopenic recipients
      induces substantial T cell expansion, differentiation, and regression of large
      established tumors without the need for in vitro manipulation. Surprisingly,
      CD4(+) T cells developed cytotoxic activity, and tumor rejection was dependent on
      class II-restricted recognition of tumors by tumor-reactive CD4(+) T cells.
      Furthermore, blockade of the coinhibitory receptor CTL-associated antigen 4 (CTLA
      4) on the transferred CD4(+) T cells resulted in greater expansion of effector T
      cells, diminished accumulation of tumor-reactive regulatory T cells, and superior
      antitumor activity capable of inducing regression of spontaneous mouse melanoma.
      These findings suggest a novel potential therapeutic role for cytotoxic CD4(+) T
      cells and CTLA-4 blockade in cancer immunotherapy, and demonstrate the potential
      advantages of differentiating tumor-reactive CD4(+) cells in vivo over current
      protocols favoring in vitro expansion and differentiation.

PMID- 20156972
TI  - Dynamic T cell migration program provides resident memory within intestinal
      epithelium.
AB  - Migration to intestinal mucosa putatively depends on local activation because
      gastrointestinal lymphoid tissue induces expression of intestinal homing
      molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult
      to reconcile with reports of intestinal T cell responses after alternative routes
      of immunization. We reconcile this discrepancy by demonstrating that activation
      within spleen results in intermediate induction of homing potential to the
      intestinal mucosa. We further demonstrate that memory T cells within small
      intestine epithelium do not routinely recirculate with memory T cells in other
      tissues, and we provide evidence that homing is similarly dynamic in humans after
      subcutaneous live yellow fever vaccine immunization. These data explain why
      systemic immunization routes induce local cell-mediated immunity within the
      intestine and indicate that this tissue must be seeded with memory T cell
      precursors shortly after activation.

PMID- 20156973
TI  - Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established
      melanoma.
AB  - In vitro differentiated CD8(+) T cells have been the primary focus of
      immunotherapy of cancer with little focus on CD4(+) T cells. Immunotherapy
      involving in vitro differentiated T cells given after lymphodepleting regimens
      significantly augments antitumor immunity in animals and human patients with
      cancer. However, the mechanisms by which lymphopenia augments adoptive cell
      therapy and the means of properly differentiating T cells in vitro are still
      emerging. We demonstrate that naive tumor/self-specific CD4(+) T cells naturally
      differentiated into T helper type 1 cytotoxic T cells in vivo and caused the
      regression of established tumors and depigmentation in lymphopenic hosts. Therapy
      was independent of vaccination, exogenous cytokine support, CD8(+), B, natural
      killer (NK), and NKT cells. Proper activation of CD4(+) T cells in vivo was
      important for tumor clearance, as naive tumor-specific CD4(+) T cells could not
      completely treat tumor in lymphopenic common gamma chain (gamma(c))-deficient
      hosts. gamma(c) signaling in the tumor-bearing host was important for survival
      and proper differentiation of adoptively transferred tumor-specific CD4(+) T
      cells. Thus, these data provide a platform for designing immunotherapies that
      incorporate tumor/self-reactive CD4(+) T cells.

PMID- 20156974
TI  - ADAM10 is essential for Notch2-dependent marginal zone B cell development and
      CD23 cleavage in vivo.
AB  - The proteolytic activity of a disintegrin and metalloproteinase 10 (ADAM10)
      regulates cell-fate decisions in Drosophila and mouse embryos. However, in utero
      lethality of ADAM10(-/-) mice has prevented examination of ADAM10 cleavage events
      in lymphocytes. To investigate their role in B cell development, we generated B
      cell-specific ADAM10 knockout mice. Intriguingly, deletion of ADAM10 prevented
      development of the entire marginal zone B cell (MZB) lineage. Additionally,
      cleavage of the low affinity IgE receptor, CD23, was profoundly impaired, but
      subsequent experiments demonstrated that ADAM10 regulates CD23 cleavage and MZB
      development by independent mechanisms. Development of MZBs is dependent on Notch2
      signaling, which requires proteolysis of the Notch2 receptor by a previously
      unidentified proteinase. Further experiments revealed that Notch2 signaling is
      severely impaired in ADAM10-null B cells. Thus, ADAM10 critically regulates MZB
      development by initiating Notch2 signaling. This study identifies ADAM10 as the
      in vivo CD23 sheddase and an important regulator of B cell development. Moreover,
      it has important implications for the treatment of numerous CD23- and Notch
      mediated pathologies, ranging from allergy to cancer.

PMID- 20156975
TI  - Patients with diffuse idiopathic skeletal hyperostosis do not have increased
      peripheral bone mineral density and geometry.
AB  - OBJECTIVES: Recent studies have suggested that areal BMD (aBMD) measured by DXA
      is elevated in patients with DISH. We used peripheral QCT (pQCT) to assess
      volumetric BMD (vBMD) and bone geometry of the radius, tibia and the third
      metacarpal bone. METHODS: Patients with established DISH and a control group of
      healthy individuals were recruited. pQCT measurements were performed at the
      distal epiphyses and mid-shafts of the radius, the tibia and the third metacarpal
      bone. At the epiphyses cross-sectional area (CSA), total BMD and trabecular BMD
      were measured. At the shafts, total bone CSA, cortical CSA, cortical wall
      thickness and cortical BMD were determined. In addition, muscle and fat CSA of
      the forearm and lower leg were assessed. Bone parameters were compared between
      the two groups using independent t-tests. RESULTS: Thirty DISH patients and 30
      controls comparable with regard to age and height were included in this study.
      None of the measured bone parameters differed between groups. CONCLUSIONS: In
      contrast to suggestions based on DXA, pQCT revealed that DISH patients do not
      have increased vBMD and bone geometry in the appendicular skeleton. Ossification
      at tendon or ligament insertion sites may lead to overestimation of aBMD if
      assessed by DXA.

PMID- 20156977
TI  - Ron Germain: Towards a grand unified theory. Interview by Amy Maxmen.

PMID- 20156976
TI  - Clinical manifestations of anti-synthetase syndrome positive for anti-alanyl-tRNA
      synthetase (anti-PL12) antibodies: a retrospective study of 17 cases.
AB  - OBJECTIVE: To describe the clinical manifestations of the anti-synthetase
      syndrome (ASS) specifically associated with anti-alanyl-tRNA (anti-PL12)
      synthetase antibodies. METHODS: In a retrospective study, 17 patients (eight
      males, nine females, mean age = 60.3 years) with ASS symptoms confirmed by two
      consecutive tests (cyto-dot and/or immunoblot, or both), with positive results
      for anti-PL12 antibodies, were included. RESULTS: All patients presented with
      interstitial lung disease (ILD), which was associated with mild myositis in 41%
      of the cases. RP and general impairment were common, whereas rheumatic and
      dermatological symptoms were uncommon. Four patients suffered from SS, and four
      others had an atypical oesophageal involvement. The long-term course was
      assessable for 10 patients (follow-up of 41.1 months). Five patients required
      immunosuppressive drugs. Two patients are waiting for a lung transplant because
      of disproportionate and refractory pulmonary hypertension. CONCLUSION: The
      severity of anti-PL12 ASS varied because of the constant pulmonary involvement.
      ILD was the predominant prognosis factor, which was notable in cases associated
      with pulmonary hypertension.

PMID- 20156978
TI  - Two decades before the mast.

PMID- 20156979
TI  - Respiratory muscle training improves cardiopulmonary function and exercise
      tolerance in subjects with subacute stroke: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether two types of exercise--breathing retraining (BRT)
      and inspiratory muscle training (IMT)--improve on cardiopulmonary functions and
      exercise tolerance in patients with stroke. DESIGN: A randomized controlled
      trial. SETTING: Education and research hospital. SUBJECTS: Forty-five inpatients
      with stroke (24 men, 21 women) were recruited for the study. The subjects were
      randomized into three groups: 15 assigned to receive inspiratory muscle training
      (IMT); 15 assigned to received breathing retraining, diaphragmatic breathing and
      pursed-lips breathing (BRT); 15 assigned to a control group. INTERVENTIONS: All
      study groups participated in a conventional stroke rehabilitation programme. For
      the same period, the IMT and BRT groups trained daily, six times a week, with
      each session consisting of one half-hour of training for six weeks. MAIN
      MEASURES: Each subject underwent pulmonary function and cardiopulmonary exercise
      tests. Subjects were also assessed for exertional dyspnoea, stages of motor
      recovery, ambulation status, activity of daily living and quality of life.
      RESULTS: After the training programme, the IMT group had significantly improved
      forced expiratory volume at 1 second (FEV(1)), forced vital capacity (FVC), vital
      capacity (VC), forced expiratory flow rate 25-75% (FEF 25-75%) and maximum
      voluntary ventilation (MVV) values compared with the BRT and control groups,
      although there were no significant differences between the BRT and control groups
      (P<0.01). Peak expiratory flow rate (PEF) value was increased significantly in
      the BTR group compared with the IMT and control groups. The IMT group also had
      significantly higher peak oxygen consumption (Vo(2peak)) than the BRT and control
      groups, although there were no significant differences between the BRT and
      control groups (P<0.001). There was a statistically significant increase in
      maximum inspiratory pressure (PI(max)) and maximum inspiratory and expiratory
      pressure (PE(max)) in the BRT group and, PI(max) in the IMT group compared with
      baseline and the control group. In the IMT group, this was associated with
      improvements in exercise capacity, sensation of dyspnoea and quality of life.
      CONCLUSIONS: Significant short-term effects of the respiratory muscle training
      programme on respiratory muscle function, exercise capacity and quality of life
      were recorded in this study.

PMID- 20156980
TI  - Errorless learning is superior to trial and error when learning a practical skill
      in rehabilitation: a randomized controlled trial.
AB  - OBJECTIVE: Errorless learning is an effective strategy for the cognitive
      rehabilitation of memory impairment, but there is little evidence to support its
      use for skill learning. This preliminary study investigates whether errorless
      learning is superior to treatment as usual (trial and error), when teaching
      people with amputations and comorbid risk of vascular cognitive impairment to fit
      a prosthetic limb. DESIGN: A randomized control design. SETTING: A regional limb
      fitting clinic at the West of Scotland Mobility and Rehabilitation Centre in
      Glasgow. PARTICIPANTS: Thirty adults with transtibial amputations, recruited from
      a regional limb-fitting clinic. Of these 42% were cognitively impaired.
      INTERVENTION: Random assignment to an errorless learning intervention (n = 15) or
      a treatment as usual control (n = 15). There were five training trials within a
      single session. Participants were then asked to fit their limb without
      assistance. MAIN MEASURES: Performance was scored from videotape recording of the
      first occasion when the participant attempted to fit their limb without
      assistance. Addenbrookes Cognitive Examination-Revised (ACE-R) was used to assess
      general cognitive functioning. RESULTS: The errorless learning group remembered
      more correct steps (mean 90.9, SD 12.1) than the control group (77.9; 8.4;
      P<0.001) and made fewer errors (mean 0.93, SD 1.3) than controls (2.1; 0.95); P
      =0.002). CONCLUSIONS: Errorless learning can benefit people with amputations in
      learning the practical skill of fitting a prosthetic limb. Further study that
      includes follow-up is warranted.

PMID- 20156981
TI  - Randomized control of extracorporeal shock wave therapy versus placebo for
      chronic decubitus ulceration.
AB  - OBJECTIVE: To assess whether extracorporeal shock wave therapy increases the rate
      of healing in chronic decubitus ulceration. DESIGN: Double-blind randomized cross
      over study. SETTING: A large, long-stay hospital specializing in the management
      of people with complex neurological disabilities. SUBJECTS: The total population
      of available patients with chronic neurological conditions and chronic decubitus
      ulceration who met the inclusion criteria. INTERVENTIONS: Ulcers were randomized
      into receiving either the extracorporeal shock wave therapy or the placebo for a
      four-week period, followed by a two-week 'washout' period followed by a four-week
      period of the cross-over treatment/ placebo. MAIN MEASURES: Measurement of the
      area of the ulceration. For each observation the average of three measurements
      were taken. RESULTS: Nine ulcers (in eight patients) were included in the study:
      five on the buttocks/sacrum/trochanter and four on the feet/ankles. All those
      with static chronic ulcers showed improved healing starting 6-8 weeks after the
      start of extracorporeal shock wave therapy, whether treated first with the
      placebo or the therapy. CONCLUSIONS: Extracorporeal shock wave therapy has a
      potential part to play in the treatment of chronic skin ulceration.

PMID- 20156982
TI  - Frequency of nocturnal hypoxia in clinically stable patients during stroke
      rehabilitation.
AB  - OBJECTIVE: Sleep disordered breathing is common in patients with cerebrovascular
      disease. Nocturnal hypoxia may lead to daytime tiredness and cognitive
      impairment, thus affecting progress. This study assessed the prevalence of
      nocturnal hypoxia during rehabilitation from stroke. DESIGN: Prospective
      observational trial. SETTING: The stroke rehabilitation wards of the North
      Staffordshire Hospital, UK and of Kreiskrankenhaus Grevenbroich, Germany.
      SUBJECTS: Adult patients on a stroke rehabilitation ward, 10 days to 3 months
      (mean 32 days, SD18) after stroke onset (n = 160). Age and local environment
      matched controls (n = 156) without a history of stroke were recruited from the
      community at both centres. MAIN MEASURES: Pulse oximetry was performed overnight
      on the day of enrolment from 21:00 to 09:00. The baseline awake oxygen
      saturation, the mean nocturnal oxygen saturation, the lowest nocturnal oxygen
      saturation and the 4% Oxygen Desaturation Index were calculated for each
      participant. RESULTS: The mean baseline awake oxygen saturation of stroke
      patients was at 95.3% (SD 1.7), 0.5% lower than that of controls (P = 0.005,
      independent t-test). The group means of the mean nocturnal oxygen saturation for
      stroke patients were 0.5% lower (at 93.8% SD 2.2) than controls (P = 0.03,
      independent t-test). The mean lowest nocturnal oxygen saturation was at 79.4% (SD
      9.9), 5.9% lower than that of the controls (P<0.001, independent t-test).
      Considerably more stroke patients (n = 67, 42%) than controls (n = 24, 15%) had >
      or =10 desaturations below the baseline per hour (P<0.001 chi-square test).
      CONCLUSION: Clinically stable stroke patients enrolled in rehabilitation
      programmes have lower oxygen saturation and more nocturnal desaturations than non
      stroke controls.

PMID- 20156983
TI  - Immediate effect of transcutaneous electrical nerve stimulation on spasticity in
      patients with spinal cord injury.
AB  - OBJECTIVE: To investigate the immediate effect of transcutaneous electrical nerve
      stimulation (TENS) on spasticity in patients with spinal cord injury. DESIGN:
      Randomized controlled trial. SETTING: Extended rehabilitation centre. SUBJECTS
      AND INTERVENTION: Eighteen subjects with spinal cord injury and symptoms of
      spasticity over lower limbs were randomly assigned to receive either 60 minutes
      of active TENS (0.25 ms, 100 Hz, 15 mA) or 60 minutes of placebo non-electrically
      stimulated TENS over the common peroneal nerve. OUTCOME MEASURES: Composite
      Spasticity Score was used to assess the spasticity level of ankle plantar flexors
      immediately before and after TENS application. Composite Spasticity Score
      consisted of Achilles tendon jerks, resistance to full-range passive ankle
      dorsiflexion and ankle clonus. Between-group statistical differences of reduction
      of Composite Spasticity Score, Achilles tendon jerks, resistance to full-range
      passive ankle dorsiflexion and ankle clonus were calculated using the Mann
      Whitney test. Within-group statistical differences of Composite Spasticity Score,
      Achilles tendon jerks, resistance to full-range passive ankle dorsiflexion and
      ankle clonus were calculated using the Wilcoxon signed ranks test. RESULTS:
      Significant reductions were shown in Composite Spasticity Score by 29.5% (p =
      0.017), resistance to full-range passive ankle dorsiflexion by 31.0% (p = 0.024)
      and ankle clonus by 29.6% (p = 0.023) in the TENS group but these reductions were
      not found in the placebo TENS group. The between-group differences of both
      Composite Spasticity Score and resistance to full-range passive ankle
      dorsiflexion were significant (p = 0.027 and p = 0.024, respectively).
      CONCLUSION: This study showed that a single session of TENS could immediately
      reduce spasticity.

PMID- 20156984
TI  - Comparison of two accelerated clinical pathways--after total knee replacement how
      fast can we really go?
AB  - OBJECTIVE: To evaluate whether a further optimization of an existing accelerated
      clinical pathway protocol after total knee replacement is feasible and improves
      postoperative outcome. DESIGN: Prospective, parallel group design. SETTING:
      Orthopaedic University Medical Centre. PATIENTS: A total of 143 patients,
      scheduled for unilateral primary total knee replacement under perioperative
      regional analgesia. INTERVENTION: Sixty-seven patients received an optimized
      accelerated clinical pathway including patient-controlled regional analgesia
      pumps, ultra-early/doubled physiotherapy and motor-driven continuous passive
      motion machine units. Seventy-six patients received a standard accelerated
      clinical pathway. MAIN MEASURES: Feasibility was defined as the proportion of
      patients successfully completing the assigned pathway. Early postoperative pain
      on a visual analogue scale, consumption of regional anaesthetics, knee range of
      motion, time out of bed, non-stop walking distance/stair climbing, circumference
      measurement and Knee Society Score on the operated leg. Possible discharge
      according to an own discharge checklist. RESULTS: All patients assigned to both
      groups successfully completed this pathway. Patients in the optimized pathway
      showed significant benefits regarding stair climbing/walking distance/time out of
      bed/circumference measurements of the thigh/Knee Society function score on the
      fifth postoperative day and stair climbing/ circumference measurements of the
      thigh on the eighth postoperative day, and reduction of the consumption of
      regional anaesthetics. No significant reduction in length of stay was observed.
      CONCLUSIONS: Early postoperative functional process indicators tended to be
      higher within the optimized pathway group, but the main effects flattened over
      the course of the first eight postoperative days.

PMID- 20156985
TI  - Genomic selection in plant breeding: from theory to practice.
AB  - We intuitively believe that the dramatic drop in the cost of DNA marker
      information we have experienced should have immediate benefits in accelerating
      the delivery of crop varieties with improved yield, quality and biotic and
      abiotic stress tolerance. But these traits are complex and affected by many
      genes, each with small effect. Traditional marker-assisted selection has been
      ineffective for such traits. The introduction of genomic selection (GS), however,
      has shifted that paradigm. Rather than seeking to identify individual loci
      significantly associated with a trait, GS uses all marker data as predictors of
      performance and consequently delivers more accurate predictions. Selection can be
      based on GS predictions, potentially leading to more rapid and lower cost gains
      from breeding. The objectives of this article are to review essential aspects of
      GS and summarize the important take-home messages from recent theoretical,
      simulation and empirical studies. We then look forward and consider research
      needs surrounding methodological questions and the implications of GS for long
      term selection.

PMID- 20156987
TI  - DNA barcoding: a six-question tour to improve users' awareness about the method.
AB  - DNA barcoding is a recent and widely used molecular-based identification system
      that aims to identify biological specimens, and to assign them to a given
      species. However, DNA barcoding is even more than this, and besides many
      practical uses, it can be considered the core of an integrated taxonomic system,
      where bioinformatics plays a key role. DNA barcoding data could be interpreted in
      different ways depending on the examined taxa but the technique relies on
      standardized approaches, methods and analyses. The existing reference towards a
      common way to treat DNA barcoding data, analyses and results is the Barcode of
      Life Data Systems. However, the scientific community has produced in the recent
      years a number of alternative methods to manage barcoding data. The present work
      starts from this point, because users should be aware of the consequences their
      choices produce on the results. Despite the fact that a strict standardization is
      the essence of DNA barcoding, we propose a tour of six questions to improve the
      users' awareness about the method, the correct use of concepts and alternative
      tools provided by scientific community.

PMID- 20156988
TI  - Wavelet-based functional linear mixed models: an application to measurement error
      corrected distributed lag models.
AB  - Frequently, exposure data are measured over time on a grid of discrete values
      that collectively define a functional observation. In many applications,
      researchers are interested in using these measurements as covariates to predict a
      scalar response in a regression setting, with interest focusing on the most
      biologically relevant time window of exposure. One example is in panel studies of
      the health effects of particulate matter (PM), where particle levels are measured
      over time. In such studies, there are many more values of the functional data
      than observations in the data set so that regularization of the corresponding
      functional regression coefficient is necessary for estimation. Additional issues
      in this setting are the possibility of exposure measurement error and the need to
      incorporate additional potential confounders, such as meteorological or co
      pollutant measures, that themselves may have effects that vary over time. To
      accommodate all these features, we develop wavelet-based linear mixed distributed
      lag models that incorporate repeated measures of functional data as covariates
      into a linear mixed model. A Bayesian approach to model fitting uses wavelet
      shrinkage to regularize functional coefficients. We show that, as long as the
      exposure error induces fine-scale variability in the functional exposure profile
      and the distributed lag function representing the exposure effect varies smoothly
      in time, the model corrects for the exposure measurement error without further
      adjustment. Both these conditions are likely to hold in the environmental
      applications we consider. We examine properties of the method using simulations
      and apply the method to data from a study examining the association between PM,
      measured as hourly averages for 1-7 days, and markers of acute systemic
      inflammation. We use the method to fully control for the effects of confounding
      by other time-varying predictors, such as temperature and co-pollutants.

PMID- 20156989
TI  - Retrocaval ureter.

PMID- 20156990
TI  - Phybase: an R package for species tree analysis.
AB  - MOTIVATION: Phybase is an R package for phylogenetic analysis using species
      trees. It provides functions to read, write, manipulate, simulate, estimate,
      summarize and plot species trees, which contain not only the topology and branch
      lengths but also population sizes. AVAILABILITY: The Phybase package is available
      at the R repository. The manual and supporting materials including source code,
      sample R code and sample data files for the species tree analysis are available
      at http://stat.osu.edu/~liuliang/research/phybase.html.

PMID- 20156991
TI  - iPHACE: integrative navigation in pharmacological space.
AB  - SUMMARY: The increasing availability of experimentally determined binding
      affinities for drugs on multiple protein targets requires the design of specific
      mining and visualization tools that graphically integrate chemical and biological
      data in an efficient environment. With this aim, we developed iPHACE, an
      integrative web-based tool to navigate in the pharmacological space defined by
      small molecule drugs contained in the IUPHAR-DB, with additional interactions
      present in PDSP. Extending beyond traditional querying and filtering tools,
      iPHACE offers a means to extract knowledge from the target profile of drugs as
      well as from the drug profile of protein targets. AVAILABILITY: iPHACE is
      available at http://cgl.imim.es/iphace/ (EU site) and
      http://agave.health.unm.edu/iphace/ (US mirror).

PMID- 20156986
TI  - The role of mitochondria in the pathogenesis of type 2 diabetes.
AB  - The pathophysiology of type 2 diabetes mellitus (DM) is varied and complex.
      However, the association of DM with obesity and inactivity indicates an
      important, and potentially pathogenic, link between fuel and energy homeostasis
      and the emergence of metabolic disease. Given the central role for mitochondria
      in fuel utilization and energy production, disordered mitochondrial function at
      the cellular level can impact whole-body metabolic homeostasis. Thus, the
      hypothesis that defective or insufficient mitochondrial function might play a
      potentially pathogenic role in mediating risk of type 2 DM has emerged in recent
      years. Here, we summarize current literature on risk factors for diabetes
      pathogenesis, on the specific role(s) of mitochondria in tissues involved in its
      pathophysiology, and on evidence pointing to alterations in mitochondrial
      function in these tissues that could contribute to the development of DM. We also
      review literature on metabolic phenotypes of existing animal models of impaired
      mitochondrial function. We conclude that, whereas the association between
      impaired mitochondrial function and DM is strong, a causal pathogenic
      relationship remains uncertain. However, we hypothesize that genetically
      determined and/or inactivity-mediated alterations in mitochondrial oxidative
      activity may directly impact adaptive responses to overnutrition, causing an
      imbalance between oxidative activity and nutrient load. This imbalance may lead
      in turn to chronic accumulation of lipid oxidative metabolites that can mediate
      insulin resistance and secretory dysfunction. More refined experimental
      strategies that accurately mimic potential reductions in mitochondrial functional
      capacity in humans at risk for diabetes will be required to determine the
      potential pathogenic role in human insulin resistance and type 2 DM.

PMID- 20156992
TI  - Abundance of type I toxin-antitoxin systems in bacteria: searches for new
      candidates and discovery of novel families.
AB  - Small, hydrophobic proteins whose synthesis is repressed by small RNAs (sRNAs),
      denoted type I toxin-antitoxin modules, were first discovered on plasmids where
      they regulate plasmid stability, but were subsequently found on a few bacterial
      chromosomes. We used exhaustive PSI-BLAST and TBLASTN searches across 774
      bacterial genomes to identify homologs of known type I toxins. These searches
      substantially expanded the collection of predicted type I toxins, revealed
      homology of the Ldr and Fst toxins, and suggested that type I toxin-antitoxin
      loci are not spread by horizontal gene transfer. To discover novel type I toxin
      antitoxin systems, we developed a set of search parameters based on
      characteristics of known loci including the presence of tandem repeats and
      clusters of charged and bulky amino acids at the C-termini of short proteins
      containing predicted transmembrane regions. We detected sRNAs for three predicted
      toxins from enterohemorrhagic Escherichia coli and Bacillus subtilis, and showed
      that two of the respective proteins indeed are toxic when overexpressed. We also
      demonstrated that the local free-energy minima of RNA folding can be used to
      detect the positions of the sRNA genes. Our results suggest that type I toxin
      antitoxin modules are much more widely distributed among bacteria than previously
      appreciated.

PMID- 20156993
TI  - Boosting the prediction and understanding of DNA-binding domains from sequence.
AB  - DNA-binding proteins perform vital functions related to transcription, repair and
      replication. We have developed a new sequence-based machine learning protocol to
      identify DNA-binding proteins. We compare our method with an extensive benchmark
      of previously published structure-based machine learning methods as well as a
      standard sequence alignment technique, BLAST. Furthermore, we elucidate important
      feature interactions found in a learned model and analyze how specific rules
      capture general mechanisms that extend across DNA-binding motifs. This analysis
      is carried out using the malibu machine learning workbench available at
      http://proteomics.bioengr.uic.edu/malibu and the corresponding data sets and
      features are available at http://proteomics.bioengr.uic.edu/dna.

PMID- 20156994
TI  - A novel nucleoid protein of Escherichia coli induced under anaerobiotic growth
      conditions.
AB  - A systematic search was performed for DNA-binding sequences of YgiP, an
      uncharacterized transcription factor of Escherichia coli, by using the Genomic
      SELEX. A total of 688 YgiP-binding loci were identified after genome-wide
      profiling of SELEX fragments with a high-density microarray (SELEX-chip). Gel
      shift and DNase-I footprinting assays indicated that YgiP binds to multiple sites
      along DNA probes with a consensus GTTNATT sequence. Atomic force microscope
      observation indicated that at low concentrations, YgiP associates at various
      sites on DNA probes, but at high concentrations, YgiP covers the entire DNA
      surface supposedly through protein-protein contact. The intracellular
      concentration of YgiP is very low in growing E. coli cells under aerobic
      conditions, but increases more than 100-fold to the level as high as the major
      nucleoid proteins under anaerobic conditions. An E. coli mutant lacking ygiP
      showed retarded growth under anaerobic conditions. High abundance and large
      number of binding sites together indicate that YgiP is a nucleoid-associated
      protein with both architectural and regulatory roles as the nucleoid proteins Fis
      and IHF. We then propose that YgiP is a novel nucleoid protein of E. coli under
      anaerobiosis and propose to rename it Dan (DNA-binding protein under anaerobic
      conditions).

PMID- 20156995
TI  - Identification of antisense RNA stem-loops that inhibit RNA-protein interactions
      using a bacterial reporter system.
AB  - Many well-characterized examples of antisense RNAs from prokaryotic systems
      involve hybridization of the looped regions of stem-loop RNAs, presumably due to
      the high thermodynamic stability of the resulting loop-loop and loop-linear
      interactions. In this study, the identification of RNA stem-loops that inhibit
      U1A protein binding to the hpII RNA through RNA-RNA interactions was attempted
      using a bacterial reporter system based on phage lambda N-mediated
      antitermination. As a result, loop sequences possessing 7-8 base complementarity
      to the 5' region of the boxA element important for functional antitermination
      complex formation, but not the U1 hpII loop, were identified. In vitro and in
      vivo mutational analysis strongly suggested that the selected loop sequences were
      binding to the boxA region, and that the structure of the antisense stem-loop was
      important for optimal inhibitory activity. Next, in an attempt to demonstrate the
      ability to inhibit the interaction between the U1A protein and the hpII RNA, the
      rational design of an RNA stem-loop that inhibits U1A-binding to a modified hpII
      was carried out. Moderate inhibitory activity was observed, showing that it is
      possible to design and select antisense RNA stem-loops that disrupt various types
      of RNA-protein interactions.

PMID- 20156996
TI  - Optimizing copy number variation analysis using genome-wide short sequence
      oligonucleotide arrays.
AB  - The detection of copy number variants (CNV) by array-based platforms provides
      valuable insight into understanding human diversity. However, suboptimal study
      design and data processing negatively affect CNV assessment. We quantitatively
      evaluate their impact when short-sequence oligonucleotide arrays are applied
      (Affymetrix Genome-Wide Human SNP Array 6.0) by evaluating 42 HapMap samples for
      CNV detection. Several processing and segmentation strategies are implemented,
      and results are compared to CNV assessment obtained using an oligonucleotide
      array CGH platform designed to query CNVs at high resolution (Agilent). We
      quantitatively demonstrate that different reference models (e.g. single versus
      pooled sample reference) used to detect CNVs are a major source of inter-platform
      discrepancy (up to 30%) and that CNVs residing within segmental duplication
      regions (higher reference copy number) are significantly harder to detect (P <
      0.0001). After adjusting Affymetrix data to mimic the Agilent experimental design
      (reference sample effect), we applied several common segmentation approaches and
      evaluated differential sensitivity and specificity for CNV detection, ranging 39
      77% and 86-100% for non-segmental duplication regions, respectively, and 18-55%
      and 39-77% for segmental duplications. Our results are relevant to any array
      based CNV study and provide guidelines to optimize performance based on study
      specific objectives.

PMID- 20156997
TI  - Histone H1 null vertebrate cells exhibit altered nucleosome architecture.
AB  - In eukaryotic nuclei, DNA is wrapped around an octamer of core histones to form
      nucleosomes, and chromatin fibers are thought to be stabilized by linker histones
      of the H1 type. Higher eukaryotes express multiple variants of histone H1;
      chickens possess six H1 variants. Here, we generated and analyzed the phenotype
      of a complete deletion of histone H1 genes in chicken cells. The H1-null cells
      showed decreased global nucleosome spacing, expanded nuclear volumes, and
      increased chromosome aberration rates, although proper mitotic chromatin
      structure appeared to be maintained. Expression array analysis revealed that the
      transcription of multiple genes was affected and was mostly downregulated in
      histone H1-deficient cells. This report describes the first histone H1 complete
      knockout cells in vertebrates and suggests that linker histone H1, while not
      required for mitotic chromatin condensation, plays important roles in nucleosome
      spacing and interphase chromatin compaction and acts as a global transcription
      regulator.

PMID- 20156998
TI  - Fish consumption and polyunsaturated fatty acids in relation to psychological
      distress.
AB  - BACKGROUND: It has been suggested that high fish consumption improves mental well
      being. The aim of this study was to assess whether high fish consumption or omega
      3 polyunsaturated fatty acid (PUFA) intake was associated with reduced self
      reported psychological distress. METHODS: We used three cross-sectional data
      sets, the nationwide Health 2000 Survey (n = 5840), the Fishermen Study on
      Finnish fishermen and their family members (n = 1282) and the Finntwin16 Study on
      young adults (n = 4986). Data were based on self-administered questionnaires,
      interviews, health examinations and blood samples. Psychological distress was
      measured using the 12-item and 21-item General Health Questionnaires (GHQs). Fish
      consumption was measured by a food frequency questionnaire (FFQ, g/day) and
      independent frequency questions (times/month). Dietary intake (g/day) and serum
      concentrations (% from fatty acids) of PUFAs were determined. Relationships were
      analysed using regression analysis. RESULTS: Regardless of the measure, fish
      consumption and omega-3 PUFA dietary intake were not associated with distress in
      any of the data sets. In contrast to the hypothesis, high serum docosahexaenoic
      acid was associated with high distress in the Fisherman Study men. Some non
      linear associations were detected between serum omega-3 PUFAs or fish consumption
      (times/month) and distress. In the Fishermen Study, the associations were
      modified by alcohol consumption, smoking and physical activity. CONCLUSIONS: Our
      results do not support the hypothesis that fish consumption or omega-3 PUFA
      intake are associated with reduced psychological distress in the general
      population or in a population with high fish consumption.

PMID- 20156999
TI  - Zinc supplementation for the prevention of acute lower respiratory infection in
      children in developing countries: meta-analysis and meta-regression of randomized
      trials.
AB  - BACKGROUND: Routine zinc supplementation is a potential intervention for the
      prevention of acute lower respiratory infection (ALRI) in developing countries.
      However, discrepant findings from recent randomized trials remain unexplained.
      METHODS: Randomized trials of zinc supplementation in young children in
      developing countries were identified by a systematic literature review. Trials
      included in the meta-analysis met specific criteria, including participants <5
      years of age, daily/weekly zinc and control supplementation for greater than 3
      months, active household surveillance for respiratory morbidity and use of a case
      definition that included at least one sign of lower respiratory tract illness.
      ALRI case definitions were classified on the basis of specificity/severity.
      Incidence rate ratios (IRRs) were pooled by random-effects models. Meta
      regression and sub-group analysis were performed to assess potential sources of
      between-study heterogeneity. RESULTS: Ten trials were eligible for inclusion (n =
      49 450 children randomized). Zinc reduced the incidence of ALRI defined by
      specific clinical criteria [IRR 0.65, 95% confidence interval (CI) 0.52-0.82],
      but had no effect on lower-specificity ALRI case definitions based on caregiver
      report (IRR 1.01, 95% CI 0.91-1.12) or World Health Organization 'non-severe
      pneumonia' (0.96, 95% CI 0.86-1.08). By meta-regression, the effect of zinc was
      associated with ALRI case definition, but not with mean baseline age, geographic
      location, nutritional status or zinc dose. CONCLUSIONS: Routine zinc
      supplementation reduced the incidence of childhood ALRI defined by relatively
      specific clinical criteria, but the effect was null if lower specificity case
      definitions were applied. The choice of ALRI case definition may substantially
      influence inferences from community trials regarding the efficacy of preventive
      interventions.

PMID- 20157000
TI  - Cohort profile: the Canadian Observational Cohort collaboration.

PMID- 20157001
TI  - A hierarchical Bayesian model for a novel sparse partial diallel crossing design.
AB  - Partial diallel crossing designs are in common use among evolutionary
      geneticists, as well as among plant and animal breeders. When the goal is to make
      statements about populations represented by a given set of lines, it is desirable
      to maximize the number of lines sampled given a set number of crosses among them.
      We propose an augmented round-robin design that accomplishes this. We develop a
      hierarchical Bayesian model to estimate quantitative genetic parameters from our
      scheme. For example, we show how to partition genetic effects into specific and
      general combining abilities, and the method provides estimates of heritability,
      dominance, and genetic correlations in the face of complex and unbalanced
      designs. We test our approach with simulated and real data. We show that although
      the models slightly overestimate genetic variances, main effects are assessed
      accurately and precisely. We also illustrate how our approach allows the
      construction of posterior distributions of combinations of parameters by
      calculating narrow-sense heritability and a genetic correlation between
      activities of two enzymes.

PMID- 20157002
TI  - Promoting and avoiding recombination: contrasting activities of the Escherichia
      coli RuvABC Holliday junction resolvase and RecG DNA translocase.
AB  - RuvABC and RecG are thought to provide alternative pathways for the late stages
      of recombination in Escherichia coli. Inactivation of both blocks the recovery of
      recombinants in genetic crosses. RuvABC resolves Holliday junctions, with RuvAB
      driving branch migration and RuvC catalyzing junction cleavage. RecG also drives
      branch migration, but no nuclease has been identified that might act with RecG to
      cleave junctions, apart from RusA, which is not normally expressed. We searched
      for an alternative nuclease using a synthetic lethality assay to screen for
      mutations causing inviability in the absence of RuvC, on the premise that a
      strain without any ability to cut junctions might be inviable. All the mutations
      identified mapped to polA, dam, or uvrD. None of these genes encodes a nuclease
      that cleaves Holliday junctions. Probing the reason for the inviability using the
      RusA Holliday junction resolvase provided strong evidence in each case that the
      RecG pathway is very ineffective at removing junctions and indicated that a
      nuclease component most probably does not exist. It also revealed new suppressors
      of recG, which were located to the ssb gene. Taken together with the results from
      the synthetic lethality assays, the properties of the mutant SSB proteins provide
      evidence that, rather than promoting recombination, a major function of RecG is
      to curb potentially pathological replication initiated via PriA protein at sites
      remote from oriC.

PMID- 20157003
TI  - Genomewide multiple-loci mapping in experimental crosses by iterative adaptive
      penalized regression.
AB  - Genomewide multiple-loci mapping can be viewed as a challenging variable
      selection problem where the major objective is to select genetic markers related
      to a trait of interest. It is challenging because the number of genetic markers
      is large (often much larger than the sample size) and there is often strong
      linkage or linkage disequilibrium between markers. In this article, we developed
      two methods for genomewide multiple loci mapping: the Bayesian adaptive Lasso and
      the iterative adaptive Lasso. Compared with eight existing methods, the proposed
      methods have improved variable selection performance in both simulation and real
      data studies. The advantages of our methods come from the assignment of adaptive
      weights to different genetic makers and the iterative updating of these adaptive
      weights. The iterative adaptive Lasso is also computationally much more efficient
      than the commonly used marginal regression and stepwise regression methods.
      Although our methods are motivated by multiple-loci mapping, they are general
      enough to be applied to other variable selection problems.

PMID- 20157004
TI  - A tetrad analysis of the basidiomycete fungus Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a basidiomycete fungus that is found worldwide and
      causes disease in humans and animal species. The fungus grows asexually as a
      budding yeast. Under laboratory conditions it is capable of sexual reproduction
      between two mating types. After cell fusion a dikaryotic filament develops, at
      the tip of which a basidium gives rise to four chains of basidiospores. Because
      the chains each comprise 10-30 spores, rather than single spores, the analysis of
      individual meiotic events has not been attempted in C. neoformans in the style of
      tetrad analyses performed in other fungal species. Here, the basidiospores from
      >100 basidia were micromanipulated and the resultant >2500 progeny analyzed for
      three genetic markers to understand the sexual process in this fungus, leading to
      four observations: (i) Marker segregation provides genetic evidence for a single
      meiotic event within the basidium followed by multiple rounds of mitosis. (ii)
      Using each basidium as an unordered tetrad, the ADE2 and URA5 genes are linked to
      their centromeres, consistent with adjacent genomic regions rich in repetitive
      elements predicted to comprise Cryptococcus centromeres. (iii) Lack of
      germination of basidiospores is attributed to aneuploidy, rather than dormancy.
      (iv) Analysis of basidiospores derived from single chains demonstrates that each
      chain can contain different genotypes. This mechanism of sexual spore production
      would benefit the species with a high rate of dispersal and at the same time aid
      in simultaneous dissemination of both mating types to new locations in the
      environment.

PMID- 20157005
TI  - Fitness epistasis and constraints on adaptation in a human immunodeficiency virus
      type 1 protein region.
AB  - Fitness epistasis, the interaction among alleles at different loci in their
      effects on fitness, has potentially important consequences for adaptive
      evolution. We investigated fitness epistasis among amino acids of a functionally
      important region of the human immunodeficiency virus type 1 (HIV-1) exterior
      envelope glycoprotein (gp120). Seven mutations putatively involved in the
      adaptation of the second conserved to third variable protein region (C2-V3) to
      the use of an alternative host-cell chemokine coreceptor (CXCR4) for cell entry
      were engineered singly and in combinations on the wild-type genetic background
      and their effects on viral infectivity were measured. Epistasis was found to be
      common and complex, involving not only pairwise interactions, but also higher
      order interactions. Interactions could also be surprisingly strong, changing
      fitness by more than 9 orders of magnitude, which is explained by some single
      mutations being practically lethal. A consequence of the observed epistasis is
      that many of the minimum-length mutational trajectories between the wild type and
      the mutant with highest fitness on cells expressing the alternative coreceptor
      are selectively inaccessible. These results may help explain the difficulty of
      evolving viruses that use the alternative coreceptor in culture and the delayed
      evolution of this phenotype in natural infection. Knowledge of common, complex,
      and strong fitness interactions among amino acids is necessary for a full
      understanding of protein evolution.

PMID- 20157006
TI  - Structure prediction-driven genetics in Saccharomyces cerevisiae identifies an
      interface between the t-RPA proteins Stn1 and Ten1.
AB  - In Saccharomyces cerevisiae, Cdc13, Stn1, and Ten1 are essential for both
      chromosome capping and telomere length homeostasis. These three proteins have
      been proposed to perform their roles at chromosome termini as a telomere
      dedicated t-RPA complex, on the basis of several parallels with the conventional
      RPA complex. In this study, we have used several approaches to test whether a
      predicted alpha-helix in the N-terminal domain of the S. cerevisiae Stn1 protein
      is required for formation of the proposed t-RPA complex, in a manner analogous to
      the comparable helix in Rpa2. Analysis of a panel of Rpa2-OB(Stn1) chimeras
      indicates that whether a chimeric protein contains the Rpa2 or Stn1 version of
      this alpha-helix dictates its ability to function in place of Rpa2 or Stn1,
      respectively. In addition, mutations introduced into a hydrophobic surface of the
      predicted Stn1 alpha-helix eliminated association with Ten1. Strikingly, allele
      specific suppression of a stn1 mutation in this helix (stn1-L164D) by a ten1
      mutation (ten1-D138Y) resulted in a restored Stn1-Ten1 interaction, supporting
      the identification of a Stn1-Ten1 interface. We conclude that Stn1 interacts with
      Ten1 through an alpha-helix, in a manner analogous to the interaction between the
      comparable subunits of the RPA complex.

PMID- 20157007
TI  - Defining neurogenetic phenotypes (or how to compare needles in haystacks).

PMID- 20157008
TI  - Mechanism of neurodegeneration of neurons with mitochondrial DNA mutations.
AB  - Mutations of mitochondrial DNA are associated with a wide spectrum of disorders,
      primarily affecting the central nervous system and muscle function. The specific
      consequences of mitochondrial DNA mutations for neuronal pathophysiology are not
      understood. In order to explore the impact of mitochondrial mutations on neuronal
      biochemistry and physiology, we have used fluorescence imaging techniques to
      examine changes in mitochondrial function in neurons differentiated from mouse
      embryonic stem-cell cybrids containing mitochondrial DNA polymorphic variants or
      mutations. Surprisingly, in neurons carrying a severe mutation in respiratory
      complex I (<10% residual complex I activity) the mitochondrial membrane potential
      was significantly increased, but collapsed in response to oligomycin, suggesting
      that the mitochondrial membrane potential was maintained by the F(1)F(o) ATPase
      operating in 'reverse' mode. In cells with a mutation in complex IV causing
      approximately 40% residual complex IV activity, the mitochondrial membrane
      potential was not significantly different from controls. The rate of generation
      of mitochondrial reactive oxygen species, measured using hydroethidium and
      signals from the mitochondrially targeted hydroethidine, was increased in neurons
      with both the complex I and complex IV mutations. Glutathione was depleted,
      suggesting significant oxidative stress in neurons with a complex I deficiency,
      but not in those with a complex IV defect. In the neurons with complex I
      deficiency but not the complex IV defect, neuronal death was increased and was
      attenuated by reactive oxygen species scavengers. Thus, in neurons with a severe
      mutation of complex I, the maintenance of a high potential by F(1)F(o) ATPase
      activity combined with an impaired respiratory chain causes oxidative stress
      which promotes cell death.

PMID- 20157010
TI  - Internodal length variability of dermal myelinated fibres.

PMID- 20157009
TI  - Imaging memory in temporal lobe epilepsy: predicting the effects of temporal lobe
      resection.
AB  - Functional magnetic resonance imaging can demonstrate the functional anatomy of
      cognitive processes. In patients with refractory temporal lobe epilepsy,
      evaluation of preoperative verbal and visual memory function is important as
      anterior temporal lobe resections may result in material specific memory
      impairment, typically verbal memory decline following left and visual memory
      decline after right anterior temporal lobe resection. This study aimed to
      investigate reorganization of memory functions in temporal lobe epilepsy and to
      determine whether preoperative memory functional magnetic resonance imaging may
      predict memory changes following anterior temporal lobe resection. We studied 72
      patients with unilateral medial temporal lobe epilepsy (41 left) and 20 healthy
      controls. A functional magnetic resonance imaging memory encoding paradigm for
      pictures, words and faces was used testing verbal and visual memory in a single
      scanning session on a 3T magnetic resonance imaging scanner. Fifty-four patients
      subsequently underwent left (29) or right (25) anterior temporal lobe resection.
      Verbal and design learning were assessed before and 4 months after surgery. Event
      related functional magnetic resonance imaging analysis revealed that in left
      temporal lobe epilepsy, greater left hippocampal activation for word encoding
      correlated with better verbal memory. In right temporal lobe epilepsy, greater
      right hippocampal activation for face encoding correlated with better visual
      memory. In left temporal lobe epilepsy, greater left than right anterior
      hippocampal activation on word encoding correlated with greater verbal memory
      decline after left anterior temporal lobe resection, while greater left than
      right posterior hippocampal activation correlated with better postoperative
      verbal memory outcome. In right temporal lobe epilepsy, greater right than left
      anterior hippocampal functional magnetic resonance imaging activation on face
      encoding predicted greater visual memory decline after right anterior temporal
      lobe resection, while greater right than left posterior hippocampal activation
      correlated with better visual memory outcome. Stepwise linear regression
      identified asymmetry of activation for encoding words and faces in the
      ipsilateral anterior medial temporal lobe as strongest predictors for
      postoperative verbal and visual memory decline. Activation asymmetry, language
      lateralization and performance on preoperative neuropsychological tests predicted
      clinically significant verbal memory decline in all patients who underwent left
      anterior temporal lobe resection, but were less able to predict visual memory
      decline after right anterior temporal lobe resection. Preoperative memory
      functional magnetic resonance imaging was the strongest predictor of verbal and
      visual memory decline following anterior temporal lobe resection. Preoperatively,
      verbal and visual memory function utilized the damaged, ipsilateral hippocampus
      and also the contralateral hippocampus. Memory function in the ipsilateral
      posterior hippocampus may contribute to better preservation of memory after
      surgery.

PMID- 20157011
TI  - Limb-shaking transient ischaemic attacks in patients with internal carotid artery
      occlusion: a case-control study.
AB  - Limb-shaking is a specific clinical feature of transient ischaemic attacks that
      has been associated with a high-grade stenosis or occlusion of the internal
      carotid artery. The aim of this study was to describe the clinical
      characteristics of limb-shaking in patients with internal carotid artery
      occlusion and to investigate whether patients with limb-shaking have a worse
      haemodynamic state of the brain than patients with internal carotid artery
      occlusion without limb-shaking. We included 34 patients (mean age 62 + or - 7
      years, 82% male) with limb-shaking associated with internal carotid artery
      occlusion and 68 sex- and age-matched controls with cerebral transient ischaemic
      attack or minor disabling ischaemic stroke associated with internal carotid
      artery occlusion, but without limb-shaking. We investigated clinical
      characteristics, collateral pathways on contrast angiograms and carbon dioxide
      reactivity measured by transcranial Doppler. The results showed that limb-shaking
      usually lasted less than 5 min and was often accompanied by paresis of the
      involved limb. Compared with controls, patients with limb-shaking more frequently
      had symptoms precipitated by rising or exercise (odds ratio 14.2, 95% confidence
      interval 4.2-47.9), more frequently had recurrent ischaemic deficits after
      documented internal carotid artery occlusion (but before inclusion in the study)
      (odds ratio 8.2, 95% confidence interval 2.3-29.3), more often had leptomeningeal
      collaterals (odds ratio 6.8, 95% confidence interval 2.0-22.7), and tended to
      have a lower carbon dioxide-reactivity (mean 5% + or - 16 versus 12% + or - 17;
      odds ratio 0.97 per 1% increase in carbon dioxide-reactivity, 95% confidence
      interval 0.94-1.00). In conclusion, limb-shaking transient ischaemic attacks in
      patients with internal carotid artery occlusion can be recognized by their short
      duration, are often accompanied by paresis and precipitated by rising or exercise
      and are indicative of an impaired haemodynamic state of the brain.

PMID- 20157012
TI  - Neuroimaging of eye position reveals spatial neglect.
AB  - Conjugate eye deviation describes the tonic horizontal deviation of the eyes in
      acute stroke patients. Here we investigate whether measuring patients' eye-in
      head position in clinical magnetic resonance imaging or computed tomography scans
      obtained at admission shows a specific relationship to spatial neglect. We
      investigated 124 continuously admitted subjects with unilateral, first-ever left-
      or right-sided stroke. To control for the possibility that the degree of eye
      deviation is related to lesion size rather than spatial neglect, overall lesion
      volume was used as a covariate in the statistical analysis. Horizontal eye-in
      head deviation on clinical brain scans appeared to be associated with spatial
      neglect rather than with brain damage per se. In contrast to the subject groups
      without the disorder, the patients with spatial neglect showed an eye-in-head
      position that was significantly deviated towards the ipsilesional right.
      Evaluation of eye-in-head position on clinical scans thus may be an additional
      helpful tool for diagnosing spatial neglect, particularly in the very early
      period of the stroke.

PMID- 20157013
TI  - Inhibiting poly(ADP-ribose) polymerase: a potential therapy against
      oligodendrocyte death.
AB  - Oligodendrocyte loss and demyelination are major pathological hallmarks of
      multiple sclerosis. In pattern III lesions, inflammation is minor in the early
      stages, and oligodendrocyte apoptosis prevails, which appears to be mediated at
      least in part through mitochondrial injury. Here, we demonstrate poly(ADP-ribose)
      polymerase activation and apoptosis inducing factor nuclear translocation within
      apoptotic oligodendrocytes in such multiple sclerosis lesions. The same
      morphological and molecular pathology was observed in an experimental model of
      primary demyelination, induced by the mitochondrial toxin cuprizone. Inhibition
      of poly(ADP-ribose) polymerase in this model attenuated oligodendrocyte depletion
      and decreased demyelination. Poly(ADP-ribose) polymerase inhibition suppressed c
      Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation,
      increased the activation of the cytoprotective phosphatidylinositol-3 kinase-Akt
      pathway and prevented caspase-independent apoptosis inducing factor-mediated
      apoptosis. Our data indicate that poly(ADP-ribose) polymerase activation plays a
      crucial role in the pathogenesis of pattern III multiple sclerosis lesions. Since
      poly(ADP-ribose) polymerase inhibition was also effective in the inflammatory
      model of multiple sclerosis, it may target all subtypes of multiple sclerosis,
      either by preventing oligodendrocyte death or attenuating inflammation.

PMID- 20157014
TI  - DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of
      Parkinson's disease.
AB  - Biomarkers are urgently needed for the diagnosis and monitoring of disease
      progression in Parkinson's disease. Both DJ-1 and alpha-synuclein, two proteins
      critically involved in Parkinson's disease pathogenesis, have been tested as
      disease biomarkers in several recent studies with inconsistent results. These
      have been largely due to variation in the protein species detected by different
      antibodies, limited numbers of patients in some studies, or inadequate control of
      several important variables. In this study, the nature of DJ-1 and alpha
      synuclein in human cerebrospinal fluid was studied by a combination of western
      blotting, gel filtration and mass spectrometry. Sensitive and quantitative
      Luminex assays detecting most, if not all, species of DJ-1 and alpha-synuclein in
      human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of
      DJ-1 and alpha-synuclein from 117 patients with Parkinson's disease, 132 healthy
      individuals and 50 patients with Alzheimer's disease were analysed using newly
      developed, highly sensitive Luminex technology while controlling for several
      major confounders. A total of 299 individuals and 389 samples were analysed. The
      results showed that cerebrospinal fluid DJ-1 and alpha-synuclein levels were
      dependent on age and influenced by the extent of blood contamination in
      cerebrospinal fluid. Both DJ-1 and alpha-synuclein levels were decreased in
      Parkinson's patients versus controls or Alzheimer's patients when blood
      contamination was controlled for. In the population aged > or = 65 years, when
      cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and alpha-synuclein,
      respectively, the sensitivity and specificity for patients with Parkinson's
      disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for alpha
      synuclein. A combination of the two markers did not enhance the test performance.
      There was no association between DJ-1 or alpha-synuclein and the severity of
      Parkinson's disease. Taken together, this represents the largest scale study for
      DJ-1 or alpha-synuclein in human cerebrospinal fluid so far, while using newly
      established sensitive Luminex assays, with controls for multiple variables. We
      have demonstrated that total DJ-1 and alpha-synuclein in human cerebrospinal
      fluid are helpful diagnostic markers for Parkinson's disease, if variables such
      as blood contamination and age are taken into consideration.

PMID- 20157016
TI  - Effects of a mail and telephone intervention on breast health behaviors.
AB  - This study evaluated a mail and telephone intervention to improve breast health
      behaviors while maintaining quality of life. Women recruited from the general
      public were randomized to a stepped-intensity intervention consisting of
      mailings, telephone calls, and counseling (if requested or appropriate given a
      woman's genetic risk for breast cancer) or to a delayed treatment control group.
      Outcomes (mammography screening and quality of life) were measured at baseline in
      a telephone survey and again at a 12-month follow-up period. Women in the
      intervention group significantly increased screening mammography uptake by 12%
      and quality of life by 5.3 scale points compared to control participants. Changes
      in knowledge of breast cancer, genetic testing, and cancer worry all
      significantly predicted intervention changes. This successful intervention can
      help women make better breast health choices without causing increased worry.

PMID- 20157015
TI  - Multi-system neurological disease is common in patients with OPA1 mutations.
AB  - Additional neurological features have recently been described in seven families
      transmitting pathogenic mutations in OPA1, the most common cause of autosomal
      dominant optic atrophy. However, the frequency of these syndromal 'dominant optic
      atrophy plus' variants and the extent of neurological involvement have not been
      established. In this large multi-centre study of 104 patients from 45 independent
      families, including 60 new cases, we show that extra-ocular neurological
      complications are common in OPA1 disease, and affect up to 20% of all mutational
      carriers. Bilateral sensorineural deafness beginning in late childhood and early
      adulthood was a prominent manifestation, followed by a combination of ataxia,
      myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the
      third decade of life onwards. We also identified novel clinical presentations
      with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple
      sclerosis-like illness. In contrast to initial reports, multi-system neurological
      disease was associated with all mutational subtypes, although there was an
      increased risk with missense mutations [odds ratio = 3.06, 95% confidence
      interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine
      triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82;
      P = 0.0271). Histochemical and molecular characterization of skeletal muscle
      biopsies revealed the presence of cytochrome c oxidase-deficient fibres and
      multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1
      mutations, even in those with isolated optic nerve involvement. However, the
      cytochrome c oxidase-deficient load was over four times higher in the dominant
      optic atrophy + group compared to the pure optic neuropathy group, implicating a
      causal role for these secondary mitochondrial DNA defects in disease
      pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had
      significantly worse visual outcomes, and careful surveillance is therefore
      mandatory to optimize the detection and management of neurological disability in
      a group of patients who already have significant visual impairment.

PMID- 20157017
TI  - Knowledge translation strategies using the thinking about epilepsy program as a
      case study.
AB  - In many areas of health promotion and health care there is a need to bring new
      knowledge from research into practice (knowledge translation). Relevant research
      alone is not usually sufficient to achieve the ultimate outcome(s) of interest.
      This study aims to address this gap by outlining practices and outcomes involved
      in moving research findings into action using the example of the Thinking About
      Epilepsy program. A case study approach is used to discuss evidence-based
      principles and steps taken to translate evidence about the Thinking About
      Epilepsy program into action. Data used to inform this process include
      organizational documents, observations, and stakeholder interviews. Partnerships
      and techniques used for knowledge translation are discussed. The process of
      moving research knowledge into action is discussed explicitly in terms of who the
      policy makers are, what action is desired, the role of partners, and funding.
      Using a case study approach the authors have illustrated the importance of
      starting knowledge translation at the beginning, not at the end, of the research
      project. The principles discussed in this article can be extended past epilepsy
      and applied to move research findings relevant to other health conditions, health
      promotion activities, products, and technologies into action.

PMID- 20157018
TI  - Competency-based impact of a statewide public health leadership training program.
AB  - Previous public health leadership training research has assessed regional or
      national programs or evaluated program effectiveness qualitatively. Although
      these methods are valuable, state-level program impact has not been evaluated
      quantitatively. Public health core and leadership competency assessments are
      administered pre and post Kansas Public Health Leadership Institute training (N =
      94). Wilcoxon signed rank tests note significant increases by each competency
      domain. Data are stratified by years of experience, level of education, and urban
      or rural status, and correlations calculated using Spearman's rho tests in
      SPSS/PC 14.0. Post training, participants improve significantly in all competency
      domains (p < .001). Participants with lower education, fewer years of experience,
      and rural status improve more in certain core competency domains. Lower education
      and rural status correlate with greater improvement in certain leadership
      competency domains. Similar assessment methods can be used by other public health
      education programs to ensure that programs appropriately train specific workforce
      populations for national accreditation.

PMID- 20157019
TI  - Association between nonsteroidal anti-inflammatory drug use and cutaneous
      squamous cell carcinoma.
AB  - OBJECTIVE: To examine the association between nonsteroidal anti-inflammatory drug
      (NSAID) use and cutaneous squamous cell carcinoma (SCC). DESIGN: Retrospective
      case-control study. SETTING: Kaiser Permanente Northern California (KPNC), a
      large population based-health maintenance organization. PATIENTS: Random sample
      of 415 KPNC members diagnosed as having a pathologically verified SCC in 2004 and
      415 age-, sex-, and race-matched controls with no history of skin cancer. MAIN
      EXPOSURE MEASURE: Self-reported NSAID use in the 10 years prior to baseline. Use
      of NSAIDs was categorized based on type (any NSAIDs, aspirin, ibuprofen, and
      nonaspirin NSAIDs). Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated using conditional logistic regression to estimate the association of
      SCC with regular use, dose, and duration of exposure to the different NSAID
      types. Information on pharmacy-dispensed NSAIDs was also examined to assess its
      association with SCC risk. Models were adjusted for all ascertained SCC risk
      factors (fully adjusted model) and only those variables associated with both SCC
      risk and NSAID use (parsimonious model). RESULTS: Fully adjusted analyses showed
      no statistically significant reduction in SCC risk with self-reported regular use
      of any NSAID (OR, 1.32; 95% CI, 0.92-1.89), aspirin (OR, 1.38; 95% CI, 0.96
      1.97), ibuprofen (OR, 0.74; 95% CI, 0.46-1.19), or nonaspirin NSAIDs (OR, 0.84;
      95% CI, 0.56-1.26). Analyses examining duration, dose, and variables combining
      duration and dose of NSAID exposure did not appreciably change results. An
      analysis using the parsimonious model showed similar results. The data on
      pharmacy-dispensed NSAIDs also showed no association with SCC risk. CONCLUSION:
      Neither self-reported nor pharmacy-dispensed NSAID exposure was associated with
      cutaneous SCC risk.

PMID- 20157020
TI  - Modification of sphingoglycolipids and sulfolipids in kidney cell lines under
      heat stress: activation of monohexosylceramide synthesis as a ceramide scavenger.
AB  - Heat stress on Madin-Darby canine kidney cells increased ceramide content to 187%
      at 40 degrees C for 24 h, and the de novo synthesis from serine increased to
      146%. Glucosylceramide (GlcCer) and galactosylceramide (GalCer) synthesis from
      ceramide, the first glycosylation step of sphingolipid metabolism in kidney
      cells, increased to 290% (GalCer) and 143% (GlcCer) after metabolic labeling with
      (14)C-glucose at 42 degrees C for 20 h. The more complex glycolipid
      lactosylceramide also increased to 151%, whereas sulfatide and ganglioside GM3
      decreased to 21% and 43%, respectively. Sulfatide (SM4s) showed optimal sulfation
      at 37 degrees C, whereas cholesterol sulfate was optimally sulfated at 40 degrees
      C. The gene expression of ceramide glucosyltransferase (GluT), ceramide
      galactosyltransferase, and GalCer sulfotransferase (GST) after 24 h culture at 42
      degrees C significantly increased to 714%, 221%, and 174%, respectively. Another
      kidney cell line, COS7, showed less activation of these transferases by heat
      stress. Although GST gene expression was higher under heat stress, SM4s synthesis
      decreased, which may have been due to increased GST sensitivity to a temperature
      higher than 37 degrees C. When we introduced the HSP70 gene into the expression
      vector and transfected the plasmid (pCDM-dHSP70) into kidney cells, GlcCer
      synthesis increased significantly. From these results, we speculated that HSP70
      may play a role in GluT gene expression to increase GlcCer and decrease
      intracellular ceramide level.

PMID- 20157021
TI  - Successful treatment of acyclovir-resistant herpes simplex virus with
      intralesional cidofovir.

PMID- 20157022
TI  - Extent and clinical consequences of antibody formation against adalimumab in
      patients with plaque psoriasis.
AB  - OBJECTIVES: To investigate the extent antibodies to adalimumab are formed in
      patients with plaque psoriasis and whether these antibodies have clinical
      consequences. Also, to examine the relationship between antibodies to adalimumab
      and adalimumab trough titers. DESIGN: Prospective observational cohort study.
      SETTING: Two Dutch dermatology departments in university hospitals. PATIENTS: All
      consecutive patients starting a regimen of adalimumab for chronic plaque
      psoriasis. Patients were screened and fulfilled the Dutch reimbursement criteria
      for adalimumab to treat psoriasis. INTERVENTION: Adalimumab treatment (per
      label). MAIN OUTCOME MEASURES: The titer of antibodies to adalimumab, the
      adalimumab trough concentration, and the Psoriasis Area and Severity Index at
      weeks 12 and 24. RESULTS: Antibodies to adalimumab were detected in 13 of 29
      patients (45%) during 24 weeks of treatment. Differences in response rates among
      patients with low, high, and no titers of antibodies to adalimumab were
      significant at weeks 12 and 24 (P = .04 and P < .001, respectively). The median
      adalimumab trough concentrations varied significantly among patients with low,
      high, and no titers of antibodies to adalimumab (1.30 [range, 0.01-5.50], 0.0
      [range, 0.0-0.0], and 9.6 [range, 0.0-22.6] mg/L, respectively; P < .001). At
      week 24, the median adalimumab trough concentrations also differed significantly
      among good responders, moderate responders, and nonresponders (9.7 [range, 0.0
      22.6], 8.9 [range, 3.2-12.6], and 0.0 [range, 0.0-13.3] mg/L, respectively; P =
      .01). CONCLUSION: Antibodies to adalimumab are associated with lower serum
      adalimumab trough concentrations and with nonresponse or loss of response to
      adalimumab in patients with plaque psoriasis.

PMID- 20157023
TI  - Successful treatment of atrophic postoperative and traumatic scarring with carbon
      dioxide ablative fractional resurfacing: quantitative volumetric scar
      improvement.
AB  - OBJECTIVE: To assess the safety and efficacy of ablative fractional resurfacing
      (AFR) for nonacne atrophic scarring. DESIGN: In this before-and-after trial, each
      scar received 3 AFR treatments and 6 months of follow-up. SETTING: Private
      academic practice. PATIENTS: Fifteen women with Fitzpatrick skin types I to IV,
      aged 21 to 66 years, presented with 22 nonacne atrophic scars between June 1 and
      November 30, 2007. Three patients (3 scars) were excluded from the study after
      receiving 1 AFR treatment and not returning for follow-up visits. The remaining
      12 patients (19 scars) completed all 3 treatments and 6 months of follow-up.
      INTERVENTIONS: Each scar received 3 AFR treatments at 1- to 4-month intervals.
      MAIN OUTCOME MEASURES: Erythema, edema, petechiae, scarring, crusting, and
      dyschromia were graded after treatment and through 6 months of follow-up. Skin
      texture, pigmentation, atrophy, and overall appearance were evaluated after
      treatment and through 6 months of follow-up by the patient and a nonblinded
      investigator. A 3-dimensional optical profiling system generated high-resolution
      topographic representations of atrophic scars for objective measurement of
      changes in scar volume and depth. RESULTS: Adverse effects of treatment were mild
      to moderate, and no scarring or delayed-onset hypopigmentation was observed. At
      the 6-month follow-up visit, patient and investigator scores demonstrated
      improvements in skin texture for all scars (patient range, 1-4 [mean, 2.79];
      investigator range, 2-4 [mean, 2.95]), pigmentation for all scars (patient range,
      1-4 [mean, 2.32]; investigator range, 1-4 [mean, 2.21]), atrophy for all scars
      (patient range, 1-4 [mean, 2.26]; investigator range, 2-4 [mean, 2.95]), and
      overall scar appearance for all scars (patient range, 2-4 [mean, 2.89];
      investigator range, 2-4 [mean, 3.05]). Image analysis revealed a 38.0% mean
      reduction of volume and 35.6% mean reduction of maximum scar depth. CONCLUSION:
      The AFR treatments represent a safe, effective treatment modality for improving
      atrophic scarring due to surgery or trauma.

PMID- 20157024
TI  - Modern moulage: evaluating the use of 3-dimensional prosthetic mimics in a
      dermatology teaching program for second-year medical students.
AB  - OBJECTIVES: To evaluate the effectiveness of a teaching method that uses 3
      dimensional (3D) silicone-based prosthetic mimics of common serious lesions and
      eruptions and to compare learning outcomes with those achieved through the
      conventional method of lectures with 2-dimensional (2D) images. DESIGN:
      Prospective and comparative. SETTING: University of Massachusetts Medical School.
      PARTICIPANTS: Ninety second-year medical students. INTERVENTION: A 1-hour
      teaching intervention using a lecture with 2D images (2D group) or using 3D
      prosthetic mimics of lesions and eruptions (3D group). MAIN OUTCOME MEASURES:
      Mean scores in the domains of morphology, lesion and rash recognition, lesion and
      rash management, and overall performance assessed at baseline, immediately after,
      and 3 months after each group's respective teaching intervention. RESULTS:
      Immediately after the teaching intervention, the 3D group had significantly
      higher mean percentage scores than did the 2D group for overall performance (71
      vs 65, P = .03), lesion recognition (65 vs 56, P = .02), and rash management (80
      vs 67, P = .01). Three months later, the 3D group still had significantly higher
      mean percentage scores than did the 2D group for lesion recognition (47 vs 40, P
      = .03). The 3D group better recognized lesions at 3 months compared with at
      baseline, whereas the 2D group was no better at recognizing lesions at 3 months
      compared with at baseline. CONCLUSIONS: Despite limited curricular time, the
      novel teaching method using 3D prosthetic mimics of lesions and eruptions
      improves immediate and long-term learning outcomes, in particular, lesion
      recognition. It is also a preferred teaching format among second-year medical
      students.

PMID- 20157025
TI  - Neonatal and early infantile cutaneous langerhans cell histiocytosis: comparison
      of self-regressive and non-self-regressive forms.
AB  - OBJECTIVES: To describe clinical and immunohistochemical findings in patients
      with cutaneous Langerhans cell histiocytosis (LCH) beginning in the first 3
      months of life and to define predictors of disease evolution. DESIGN:
      Observational retrospective survey from July 15, 1989, to April 30, 2007.
      SETTING: Referral center in pediatric dermatology. PATIENTS: Thirty-one patients
      with a diagnosis of cutaneous LCH in the first 3 months of life and no previous
      visceral LCH. MAIN OUTCOME MEASURES: Cutaneous lesion characteristics, regulatory
      T-lymphocyte density, and E-cadherin expression were assessed. Data were compared
      between the patient groups with self-regressive vs non-self-regressive forms of
      cutaneous LCH. Pathologic analysis was performed blinded to patient group.
      RESULTS: Self-regressive cutaneous LCH was found in 21 patients and non-self
      regressive cutaneous LCH in 10 patients. Monolesional forms, necrotic lesions,
      hypopigmented macules at presentation, and distal topography of limb lesions were
      seen only in patients with self-regressive cutaneous LCH. Regulatory T-lymphocyte
      density correlated with interleukin 10 expression in lesions (r = 0.77, P = .003)
      but was not predictive of disease evolution. E-cadherin expression by Langerhans
      cells was found in 7 patients with disease limited to the skin whether self
      regressive or not. One patient with secondary disseminated disease showed loss of
      E-cadherin expression in Langerhans cells. CONCLUSIONS: Some morphologic traits
      of skin lesions can orient the diagnosis to a self-regressive form of cutaneous
      LCH. Regulatory T-lymphocyte density does not seem to be predictive of disease
      evolution. E-cadherin expression seems to be an indicator of limited skin disease
      but not of disease regression. Additional immunohistochemical study is required
      to confirm these data.

PMID- 20157026
TI  - Predicting migraine responsiveness to botulinum toxin type A injections.
AB  - BACKGROUND: Botulinum toxin type A (BTX) is used prophylactically to reduce the
      frequency of migraine headaches, with inconsistent responses reported in the
      literature. The purpose of our study was to determine whether BTX injections at
      doses used for upper-face cosmetic purposes, which differ from doses typically
      used by headache specialists, could prevent imploding and ocular but not
      exploding migraines. OBSERVATIONS: Study participants were recruited among
      patients who had received or were planning to receive BTX injections for upper
      face cosmetic purposes but also reported having migraines. Among the 18 patients
      who completed the study, most with imploding and ocular migraines experienced a
      significant reduction in their headache frequency, whereas those with exploding
      migraines generally did not. CONCLUSIONS: Our study supports the hypothesis that
      patients with imploding and ocular migraines are more responsive to BTX than
      those with exploding migraines. Injections of BTX at doses appropriate for
      cosmetic purposes may be sufficient to prevent migraine attacks.

PMID- 20157027
TI  - Cutaneous macroglobulinosis: a report of 2 cases.
AB  - BACKGROUND: Specific cutaneous lesions of Waldenstrom macroglobulinemia are rare
      and include neoplastic cell infiltrates, IgM bullous disease, and so-called IgM
      storage papules, which characterize cutaneous macroglobulinosis (CM).
      OBSERVATIONS: We report 2 patients with CM. In patient 1, CM started as small
      papules, as reported in most of the previously published case studies of CM. In
      patient 2, lesion evolution was remarkable by its severity, with large ulcerated
      nodules, and the disease progressed rapidly. As mentioned for half the previously
      described patients, peripheral neuropathy was suspected in patient 2 and
      demonstrated in patient 1, with production of antibodies to myelin-associated
      glycoprotein. CONCLUSIONS: To the best of our knowledge, rituximab treatment of
      Waldenstrom macroglobulinemia associated with CM has not been described
      previously. Rituximab caused complete remission of the lesions in patient 1,
      whereas disease rapidly progressed in patient 2, and the patient died. These
      observations suggest that evolution of the cutaneous IgM-storage lesions reflects
      that of the underlying Waldenstrom macroglobulinemia, and CM is not a prognostic
      marker.

PMID- 20157028
TI  - Cystic fibrosis presenting with dermatitis.
AB  - BACKGROUND: Patients with cystic fibrosis classically present with evidence of
      pulmonary disease, exocrine pancreatic insufficiency, and high sweat chloride
      concentrations. Dermatitis as an initial manifestation of the disease is uncommon
      and has been attributed to multiple nutritional deficiencies. OBSERVATION: We
      describe the case of a 3-month-old female infant with cystic fibrosis presenting
      with dermatitis in the setting of protein-energy malnutrition. A review of the
      laboratory study results in this case and others showed that a deficiency in
      zinc, essential fatty acids, and protein likely contributes to the development of
      the rash seen in cystic fibrosis. CONCLUSIONS: Given the frequent delay in
      diagnosis, as well as the increased morbidity and mortality associated with
      protein-energy malnutrition in these patients, it is important to consider cystic
      fibrosis as a possible diagnosis in any infant presenting with a rash and other
      signs of malnutrition. The relative contribution of specific nutritional
      deficiencies and the degree to which they influence and interact with each other
      in producing the dermatitis remain unclear, although they may all affect a common
      underlying metabolic pathway.

PMID- 20157029
TI  - Anetodermic primary cutaneous B-cell lymphoma: a unique clinicopathological
      presentation of lymphoma possibly associated with antiphospholipid antibodies.
AB  - BACKGROUND: Primary cutaneous B-cell lymphoma manifested by anetoderma has been
      reported in 7 cases. In all, the secondary anetoderma developed in lesions of
      marginal-zone lymphoma or posttransplant lymphoproliferative disorder resembling
      marginal-zone lymphoma. The mechanisms underlying the destruction of elastic
      tissue in anetoderma are unclear. However, there is growing evidence linking
      primary anetoderma with a wide range of immunologic abnormalities, the most
      common being the presence of antiphospholipid antibodies. OBSERVATIONS: We
      analyzed data from 5 patients (3 male, 2 female) with clinical and
      histopathological features of anetodermic primary cutaneous B-cell lymphoma.
      Three had marginal-zone lymphoma and 2 had follicle-center cell lymphoma. In all,
      secondary anetoderma developed in self-regressing nodules/plaques of the
      lymphoma. Two patients also had lesions clinically and histopathologically
      compatible with primary anetoderma. Associated immunologic diseases were systemic
      lupus erythematosus-like disease and rheumatoid arthritis (1 patient each; not in
      patients with primary anetoderma). Antiphospholipid antibodies were found in 4
      patients. CONCLUSIONS: Anetodermic primary cutaneous B-cell lymphoma is a rare
      and unique clinicopathological manifestation not only of marginal-zone lymphoma,
      as previously described, but also of follicle-center cell lymphoma. This type of
      secondary anetoderma, like primary anetoderma, might be associated with
      immunologic disorders, particularly antiphospholipid antibodies.

PMID- 20157030
TI  - Strategies for treatment with anti-tumor necrosis factor agents in psoriasis:
      maintaining efficacy and safety for the long haul.

PMID- 20157031
TI  - Them's the breaks: creature of broken habits.

PMID- 20157032
TI  - A nontender nodule on the tip of the left index finger.

PMID- 20157033
TI  - Superficial flaccid bullae in a female neonate.

PMID- 20157034
TI  - Infantile erythroderma.

PMID- 20157035
TI  - Purpuric eruption in a patient treated with systemic steroids.

PMID- 20157036
TI  - Treatment nonadherence and long-term effects of narrowband UV-B therapy in
      patients with psoriasis.

PMID- 20157037
TI  - Pilot study using teledermatology to manage high-need patients with psoriasis.

PMID- 20157038
TI  - Risk of hepatic hemangiomas in infants with large hemangiomas.

PMID- 20157039
TI  - The problem with "pruritis".

PMID- 20157040
TI  - Monoclonal gammopathy of undetermined significance and incidentally identified
      cutaneous monotypic plasma cell infiltrates in the absence of specific skin
      lesions.

PMID- 20157041
TI  - Speckled lentiginous nevi: no longer one single disorder.

PMID- 20157042
TI  - Rare cutaneous manifestation of prostate cancer.

PMID- 20157043
TI  - Livedoid and necrotic skin lesions due to intra-arterial buprenorphine injections
      evidenced by maltese cross-shaped histologic bodies.

PMID- 20157044
TI  - Rare cutaneous manifestation of hyperbilirubinemia.

PMID- 20157045
TI  - Cutaneous larva migrans complicated by Loffler syndrome.

PMID- 20157046
TI  - Successful use of mizoribine to treat recurrent corticosteroid-resistant palpable
      purpura in a patient with henoch-schonlein purpura nephritis.

PMID- 20157047
TI  - Hypertrophic scarring after treatment with fluorouracil, 2%, in pyruvic acid,
      98%, for verruca vulgaris.

PMID- 20157048
TI  - Dermoscopy of white fibrous papulosis of the neck.

PMID- 20157049
TI  - Pentaerythritol tetranitrate improves angiotensin II-induced vascular dysfunction
      via induction of heme oxygenase-1.
AB  - The organic nitrate pentaerythritol tetranitrate is devoid of nitrate tolerance,
      which has been attributed to the induction of the antioxidant enzyme heme
      oxygenase (HO)-1. With the present study, we tested whether chronic treatment
      with pentaerythritol tetranitrate can improve angiotensin II-induced vascular
      oxidative stress and dysfunction. In contrast to isosorbide-5 mononitrate (75
      mg/kg per day for 7 days), treatment with pentaerythritol tetranitrate (15 mg/kg
      per day for 7 days) improved the impaired endothelial and smooth muscle function
      and normalized vascular and cardiac reactive oxygen species production
      (mitochondria, NADPH oxidase activity, and uncoupled endothelial NO synthase), as
      assessed by dihydroethidine staining, lucigenin-enhanced chemiluminescence, and
      quantification of dihydroethidine oxidation products in angiotensin II (1 mg/kg
      per day for 7 days)-treated rats. The antioxidant features of pentaerythritol
      tetranitrate were recapitulated in spontaneously hypertensive rats. In addition
      to an increase in HO-1 protein expression, pentaerythritol tetranitrate but not
      isosorbide-5 mononitrate normalized vascular reactive oxygen species formation
      and augmented aortic protein levels of the tetrahydrobiopterin-synthesizing
      enzymes GTP-cyclohydrolase I and dihydrofolate reductase in angiotensin II
      treated rats, thereby preventing endothelial NO synthase uncoupling.
      Haploinsufficiency of HO-1 completely abolished the beneficial effects of
      pentaerythritol tetranitrate in angiotensin II-treated mice, whereas HO-1
      induction by hemin (25 mg/kg) mimicked the effect of pentaerythritol
      tetranitrate. Improvement of vascular function in this particular model of
      arterial hypertension by pentaerythritol tetranitrate largely depends on the
      induction of the antioxidant enzyme HO-1 and identifies pentaerythritol
      tetranitrate, in contrast to isosorbide-5 mononitrate, as an organic nitrate able
      to improve rather than to worsen endothelial function.

PMID- 20157050
TI  - A leakage leads to failure: roles of sarcoplasmic reticulum Ca2+ leak via RyR2 in
      heart failure progression.

PMID- 20157051
TI  - Direct angiotensin II type 2 receptor stimulation acts anti-inflammatory through
      epoxyeicosatrienoic acid and inhibition of nuclear factor kappaB.
AB  - Angiotensin II type 2 (AT(2)) receptors can be regarded as an endogenous repair
      system, because the AT(2) receptor is upregulated in tissue damage and mediates
      tissue protection. A potential therapeutic use of this system has only recently
      come within reach through synthesis of the first selective, orally active,
      nonpeptide AT(2) receptor agonist, compound 21 (C21; dissociation constant for
      AT(2) receptor: 0.4 nM; dissociation constant for angiotensin II type 1 receptor:
      >10,000 nM). This study tested AT(2) receptor stimulation with C21 as a potential
      future therapeutic approach for the inhibition of proinflammatory cytokines and
      of nuclear factor kappaB. C21 dose-dependently (1 nM to 1 micromol/L) reduced
      tumor necrosis factor-alpha-induced interleukin 6 levels in primary human and
      murine dermal fibroblasts. AT(2) receptor specificity was controlled for by
      inhibition with the AT(2) receptor antagonist PD123319 and by the absence of
      effects in AT(2) receptor-deficient cells. AT(2) receptor-coupled signaling
      leading to reduced interleukin 6 levels involved inhibition of nuclear factor
      kappaB, activation of protein phosphatases, and synthesis of epoxyeicosatrienoic
      acid. Inhibition of interleukin 6 promoter activity by C21 was comparable in
      strength to inhibition by hydrocortisone. C21 also reduced monocyte
      chemoattractant protein 1 and tumor necrosis factor-alpha in vitro and in
      bleomycin-induced toxic cutaneous inflammation in vivo. This study is the first
      to show the anti-inflammatory effects of direct AT(2) receptor stimulation in
      vitro and in vivo by the orally active, nonpeptide AT(2) receptor agonist C21.
      These data suggest that pharmacological AT(2) receptor stimulation may be an
      orally applicable future therapeutic approach in pathological settings requiring
      the reduction of interleukin 6 or inhibition of nuclear factor kappaB.

PMID- 20157052
TI  - Accelerated development of pressure overload-induced cardiac hypertrophy and
      dysfunction in an RyR2-R176Q knockin mouse model.
AB  - In response to chronic hypertension, the heart compensates by hypertrophic
      growth, which frequently progresses to heart failure. Although intracellular
      calcium (Ca(2+)) has a central role in hypertrophic signaling pathways, the
      Ca(2+) source for activating these pathways remains elusive. We hypothesized that
      pathological sarcoplasmic reticulum Ca(2+) leak through defective cardiac
      intracellular Ca(2+) release channels/ryanodine receptors (RyR2) accelerates
      heart failure development by stimulating Ca(2+)-dependent hypertrophic signaling.
      Mice heterozygous for the gain-of-function mutation R176Q/+ in RyR2 and wild-type
      mice were subjected to transverse aortic constriction. Cardiac function was
      significantly lower, and cardiac dimensions were larger at 8 weeks after
      transverse aortic constriction in R176Q/+ compared with wild-type mice. R176Q/+
      mice displayed an enhanced hypertrophic response compared with wild-type mice as
      assessed by heart weight:body weight ratios and cardiomyocyte cross-sectional
      areas after transverse aortic constriction. Quantitative PCR revealed increased
      transcriptional activation of cardiac stress genes in R176Q/+ mice after
      transverse aortic constriction. Moreover, pressure overload resulted in an
      increased sarcoplasmic reticulum Ca(2+) leak, associated with higher expression
      levels of the exon 4 splice form of regulator of calcineurin 1, and a decrease in
      nuclear factor of activated T-cells phosphorylation in R176Q/+ mice compared with
      wild-type mice. Taken together, our results suggest that RyR2-dependent
      sarcoplasmic reticulum Ca(2+) leak activates the prohypertrophic
      calcineurin/nuclear factor of activated T-cells pathway under conditions of
      pressure overload.

PMID- 20157053
TI  - Incremental predictive value of adding past blood pressure measurements to the
      Framingham hypertension risk equation: the Whitehall II Study.
AB  - Records of repeated examinations of blood pressure are increasingly available for
      primary care patients, but the use of this information in predicting incident
      hypertension remains unclear, because cohort studies with repeat blood pressure
      monitoring are rare. We compared the incremental value of using data on blood
      pressure history to a single measure as in the Framingham hypertension risk
      score, a validated hypertension risk prediction algorithm. Participants were 4314
      London-based civil servants (1297 women) aged 35 to 68 years who were free from
      prevalent hypertension, diabetes mellitus, and coronary heart disease at baseline
      examination (the Whitehall II Study). Standard clinical examinations of blood
      pressure, weight and height, current cigarette smoking, and parental history of
      hypertension were undertaken on a 5-year basis. A total of 1052 incident (new
      onset) cases of hypertension were observed in two 5-year baseline follow-up data
      cycles. Comparison of the Framingham risk score with a score additionally
      incorporating 5-year blood pressure history showed, at best, modest improvements
      in indicators of predictive performance: C statistics (0.796 versus 0.799),
      predicted:observed ratios (1.04 [95% CI: 0.95 to 1.15] versus 0.98 [95% CI: 0.89
      to 1.08]), or Hosmer-Lemeshow chi(2) values (11.5 versus 6.5). The net
      reclassification improvement with the modified score was 9.3% (95% CI: 4.2% to
      14.4%), resulting from a net 17.1% increase in nonhypertensives correctly
      identified as being at lower risk but a net 7.8% increase in hypertensives
      incorrectly identified as at lower risk. These data suggest that, despite the net
      reclassification improvement, the clinical use of adding repeat measures of blood
      pressure to the Framingham hypertension risk score may be limited.

PMID- 20157054
TI  - C-reactive protein promotes cardiac fibrosis and inflammation in angiotensin II
      induced hypertensive cardiac disease.
AB  - C-reactive protein (CRP) is a risk factor or biomarker for cardiovascular
      diseases, including hypertension. The present study investigated the functional
      importance of human CRP in hypertensive cardiac remodeling by a chronic infusion
      of angiotensin II (Ang II) into mice that express human CRP. Compared with the
      wild-type mice, although Ang II infusion caused an equally high systolic blood
      pressure, levels of human CRP were further elevated, and cardiac remodeling was
      markedly exacerbated in mice that express human CRP, resulting in a significant
      reduction in the left ventricular ejection fraction and fractional shortening and
      an increase in cardiac fibrosis (collagen I and III and alpha-smooth muscle
      actin) and inflammation (interleukin 1beta and tumor necrosis factor-alpha). The
      enhancement in cardiac remodeling in mice that express human CRP was associated
      with further upregulation of the Ang II type I receptor and transforming growth
      factor-beta1 and overactivation of both transforming growth factor-beta/Smad and
      nuclear factor-kappaB signaling pathways. Furthermore, in vitro studies in
      cardiac fibroblasts revealed that CRP alone was able to significantly induce
      expression of the Ang II type I receptor, collagen I/III, and alpha-smooth muscle
      actin, as well as proinflammation cytokines (interleukin 1beta and tumor necrosis
      factor-alpha), which was further enhanced by addition of Ang II. In conclusion,
      CRP is not only a biomarker but also a mediator in Ang II-mediated cardiac
      remodeling. Enhanced upregulation of the Ang II type I receptor and activation of
      the transforming growth factor-beta/Smad and nuclear factor-kappaB signaling
      pathways may be the mechanisms by which CRP promotes cardiac fibrosis and
      inflammation under high Ang II conditions.

PMID- 20157055
TI  - Clinical usefulness of positron emission tomography-computed tomography in
      recurrent thyroid carcinoma.
AB  - OBJECTIVES: To determine the efficacy of combined positron emission tomography
      computed tomography (PET-CT) in identifying recurrent thyroid cancer and to
      elucidate its role in the clinical management of thyroid carcinoma. DESIGN:
      Retrospective study. SETTING: Tertiary care referral academic center. PATIENTS:
      One hundred twenty-four patients with previously treated thyroid carcinoma who
      underwent PET-CT. MAIN OUTCOME MEASURES: PET-CT images were correlated with
      clinicopathologic information. The influence of PET-CT findings on disease status
      determination and the treatment plan was evaluated. RESULTS: Among 121 patients
      undergoing iodine I 131 ((131)I) imaging (an (131)I image was unavailable for 3
      patients), 80.6% had negative findings on (131)I imaging before undergoing PET
      CT. Among 75 patients who had positive findings on PET-CT, 71 were true positive
      results. Among 49 patients who had negative findings on PET-CT, 32 were true
      negative results. Therefore, PET-CT demonstrated a sensitivity of 80.7%,
      specificity of 88.9%, positive predictive value of 94.7%, and negative predictive
      value of 65.3%. A significant difference was noted in the mean serum
      thyroglobulin levels between patients with positive vs negative PET-CT findings
      (192.1 vs 15.0 ng/mL, P = .01) (to convert thyroglobulin level to micrograms per
      liter, multiply by 1.0). Overall, distant metastases were detected in 20.2% of
      patients using PET-CT. There was an alteration of the treatment plan in 28.2% of
      patients as a result of added PET-CT information, and 21.0% of patients underwent
      additional surgery. CONCLUSIONS: PET-CT is usually performed in patients with
      thyroid cancer having elevated thyroglobulin levels but non-(131)I-avid tumors
      and has high diagnostic accuracy for identifying local, regional, and distant
      metastases. Additional information from PET-CT in patients with (131)I-negative
      and thyroglobulin-positive tumors frequently guides the clinical management of
      recurrent thyroid carcinoma.

PMID- 20157057
TI  - Surgical treatment of buccofacial region vascular anomalies using an intraoral
      buccomucosal flap procedure.
AB  - OBJECTIVE: To report our experience in and our surgical technique of treating
      vascular anomalies of the buccofacial region using an intraoral buccomucosal flap
      approach. DESIGN: Retrospective medical record review and illustration of a
      specific surgical procedure. SETTING: Academic tertiary care center. PATIENTS:
      Thirty-two patients with vascular anomalies of the buccofacial region who have
      been treated using the intraoral buccomucosal flap approach. INTERVENTION:
      Surgical therapy using an intraoral buccomucosal flap approach. MAIN OUTCOME
      MEASURES: Surgical outcomes and complications. RESULTS: Thirty-two patients were
      treated using the intraoral buccomucosal flap approach. The vascular anomalies
      treated at this site were venous malformations (17 [53.1%]), lymphatic
      malformations (13 [40.6%]), and hemangiomas (2 [6.3%]). Surgical removal was
      accomplished without occurrence of facial nerve dysfunction or other morbidity.
      The most frequent postoperative problem encountered was scarring with lymphatic
      malformation treatment. CONCLUSION: The intraoral buccomucosal flap procedure is
      an effective surgical technique for treating vascular anomalies of the
      buccofacial region.

PMID- 20157056
TI  - Time-resolved fluorescence spectroscopy as a diagnostic technique of oral
      carcinoma: Validation in the hamster buccal pouch model.
AB  - OBJECTIVE: To investigate the benefit of using time-resolved, laser-induced
      fluorescence spectroscopy for diagnosing malignant and premalignant lesions of
      the oral cavity. DESIGN: The carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) was
      applied to 1 cheek pouch of 19 hamsters. The contralateral pouch and the cheek
      pouches of 3 hamsters without DMBA exposure served as controls. SETTING:
      University of California, Davis. PARTICIPANTS: Twenty-two golden/Syrian hamsters.
      INTERVENTION: A nitrogen pulse laser was used to induce tissue autofluorescence
      between the wavelengths of 360 and 650 nm. MAIN OUTCOME MEASURES: Spectral
      intensities and time-domain measurements were obtained and compared with the
      histopathologic findings at each corresponding site. RESULTS: Spectral
      intensities and lifetime values at 3 spectral bands (SBs; SB1 = 380 +/- 10 nm;
      SB2 = 460 +/- 10 nm, and SB3 = 635 +/- 10 nm) allowed for discrimination among
      healthy epithelium, dysplasia, carcinoma in situ, and invasive carcinoma. The
      lifetime values at SB2 were the most important when distinguishing the lesions
      using only time-resolved parameters. An algorithm combining spectral fluorescence
      parameters derived from both spectral and time-domain parameters (peak
      intensities, average fluorescence lifetimes, and the Laguerre coefficient [zero
      order]) for healthy epithelium, dysplasia, carcinoma in situ, and invasive
      carcinoma provided the best diagnostic discrimination, with 100%, 100%, 69.2%,
      and 76.5% sensitivity and 100%, 92.2%, 97.1%, and 96.2% specificity,
      respectively. CONCLUSIONS: The addition of time-resolved fluorescence-derived
      parameters significantly improves the capability of fluorescence spectroscopy
      based diagnostics in the hamster buccal pouch. This technique provides a
      potential noninvasive diagnostic instrument for head and neck cancer.

PMID- 20157058
TI  - Thyroid cancer outcomes in Filipino patients.
AB  - OBJECTIVE: To compare the outcomes of patients having thyroid cancer among
      Filipinos vs non-Filipinos. DESIGN: Retrospective medical record review. SETTING:
      High-volume tertiary referral center in Toronto, Ontario, Canada. PATIENTS: A
      total of 499 patients with thyroid cancer (36 Filipino and 463 non-Filipino)
      treated at Mount Sinai Hospital from January 1, 1984, to August 31, 2003, with a
      minimum 5-year follow-up period and a minimum 1.0-cm tumor size. Patients were
      identified from a thyroid cancer database. Data on patient, tumor, and treatment
      factors were collected along with outcomes. MAIN OUTCOME MEASURES: The presence
      of thyroid cancer recurrence, the rate of death from disease, and the time to
      recurrence. RESULTS: The 2 groups were similar for sex, age, history of head and
      neck radiation exposure, family history of thyroid cancer, follow-up time, tumor
      size, tumor pathologic findings, presence of tumor multifocality, stage of
      primary disease, type of thyroid surgery, use of postoperative radioactive iodine
      therapy, and use of external beam radiation therapy. Filipino patients
      experienced a thyroid cancer recurrence rate of 25% compared with 9.5% for non
      Filipino patients (odds ratio, 3.20; 95% confidence interval, 1.23-7.49; P =
      .004). On multivariate analysis, the increased risk of thyroid cancer recurrence
      persisted for Filipino patients (odds ratio, 6.99; 95% confidence interval, 2.31
      21.07; P < .001). No significant differences were noted between Filipino patients
      and non-Filipino patients regarding the rate of death from disease (5.6% vs 1.9%)
      and the time to recurrence (52.6 vs 53.1 months). CONCLUSIONS: Filipino patients
      have a significantly higher risk of thyroid cancer recurrence compared with non
      Filipino patients. However, no significant difference was noted in the time to
      recurrence or the rate of death from disease. These findings justify a more
      aggressive initial management and follow-up regimen for Filipino patients with
      thyroid cancer.

PMID- 20157059
TI  - Role of radiotherapy in the treatment of nasoethmoidal adenocarcinoma.
AB  - OBJECTIVE: To assess the efficacy of radiotherapy in the treatment of
      nasoethmoidal adenocarcinoma. DESIGN: Multicenter, retrospective study. SETTING:
      Eleven French hospitals. PATIENTS: The medical records of 418 patients who
      presented with nasoethmoidal adenocarcinoma from January 1, 1976, through
      December 31, 2001, were evaluated. A total of 324 patients were treated with a
      combination of surgery and radiotherapy, and 55 were treated with surgery only.
      MAIN OUTCOME MEASURES: Survival rates, disease recurrence, and postoperative
      complications. RESULTS: The 5-year Kaplan-Meier survey revealed survival rates of
      64.5% for the surgery-only group and 70.8% for the combined-treatment group. In
      the surgery-only group, 28 patients (51%) had disease recurrence (24 local, 2
      regional, and 2 distant). Of the 55 patients in the combined-treatment group, 31
      patients (56%) had disease recurrence (29 local, 1 regional, and 1 distant).
      Immediate postoperative complications in the combined-treatment group were
      hemorrhages in 2 patients, meningitis in 3 patients, and cerebrospinal fluid
      leakage in 4 patients, but no deaths occurred. In the surgery-only group, 1
      patient had meningitis, 2 had cerebrospinal fluid leaking but no hemorrhage, and
      5 died postoperatively. CONCLUSION: The results of this retrospective study
      suggest that radiotherapy can be used to treat nasoethmoidal adenocarcinoma, but
      its usefulness should be confirmed with further prospective studies.

PMID- 20157060
TI  - The impact of baseline intact parathyroid hormone levels on severity of primary
      hyperparathyroidism and outcomes in patients undergoing surgery.
AB  - OBJECTIVE: To determine the impact of intact parathyroid hormone (iPTH) baseline
      levels on severity of primary hyperparathyroidism (PHPT) and outcomes following
      parathyroidectomy for PHPT. DESIGN: Single institution retrospective review.
      SETTING: Academic tertiary care center. PATIENTS: A total of 447 consecutive
      patients undergoing parathyroid surgery for PHPT. MAIN OUTCOME MEASURES:
      Comparison of patients with high (> or =150 pg/mL) and low (<150 pg/mL) baseline
      iPTH values; preoperative serum calcium, alkaline phosphatase, and 25
      hydroxyvitamin D levels; and 6-month postoperative serum calcium and iPTH levels.
      RESULTS: A total of 304 patients had baseline iPTH values of at least 150 pg/mL
      (high baseline group), and 143 patients had baseline iPTH values lower than 150
      pg/mL (low baseline group). Patients in the high baseline group had significantly
      higher levels of preoperative serum calcium, serum alkaline phosphatase, and
      adenoma weights (P < .001 for all comparisons). Serum 25-hydroxyvitamin D levels
      were significantly lower in patients in the high baseline group (P < .001).
      Sestamibi scans were more likely to localize an adenoma in the high baseline
      group (83.7%) than in the low baseline group (68.9%) (P < .01). There were no
      differences in the serum calcium and iPTH levels between the 2 groups 6 months
      after surgery. CONCLUSIONS: Patients in the high baseline group undergoing
      surgery for PHPT had higher baseline levels of serum calcium, serum alkaline
      phosphatase, and parathyroid adenoma weights and lower serum 25-hydroxyvitamin D
      levels compared with the lower baseline group. Sestamibi scans were more likely
      to localize an adenoma in the high baseline group (83.7%) than in the low
      baseline group (68.9%) (P < .01). Despite an apparently lower rate of positive
      preoperative sestamibi scans for the low baseline group, patients were able to
      achieve a similar rate of disease cure as other patients with higher baseline
      iPTH levels. It seems that baseline iPTH level should not be used as a criterion
      to perform surgery or not perform surgery for patients with PHPT.

PMID- 20157061
TI  - Oncolysis using herpes simplex virus type 1 engineered to express cytosine
      deaminase and a fusogenic glycoprotein for head and neck squamous cell carcinoma.
AB  - OBJECTIVE: To determine if prodrug conversion of fluorocytosine to fluorouracil
      by an engineered herpes virus, OncoVEX(GALV/CD), enhances oncolytic therapy of
      head and neck squamous cell carcinoma. DESIGN: We assessed the ability of
      OncoVEX(GALV/CD) and OncoVEX(GFP) to infect, replicate within, and lyse 4 head
      and neck squamous cell carcinoma lines in vitro. The effects of adding
      fluorocytosine with OncoVEX(GALV/CD) were evaluated. RESULTS: Head and neck
      squamous cell carcinoma was permissive to green fluorescent protein expression
      in100% of cells by OncoVEX(GFP) at a multiplicity of infection of 1 after 48
      hours and supported logarithmic viral replication. Virus caused more than 60%
      cell death 6 days after exposure to virus at a multiplicity of infection of 0.1
      in 3 of the 4 cell lines. Fluorocytosine did not enhance cytotoxicity induced by
      OncoVEX(GALV/CD) at a multiplicity of infection of 0.1. However, for the least
      sensitive SCC25 cell line, virus at a multiplicity of infection of 0.01 was
      cytotoxic to only 4% of cells after 6 days but was cytotoxic to 35% of cells with
      fluorocytosine. CONCLUSIONS: OncoVEX(GALV/CD) efficiently infects, replicates
      within, and lyses head and neck squamous cell carcinoma at relatively low viral
      doses. Prodrug conversion by cytosine deaminase did not enhance therapy at viral
      doses that cause efficient cytotoxicity but may have beneficial effects in less
      sensitive cell lines at low viral doses.

PMID- 20157062
TI  - Reproducibility of clinical grading of tonsillar size.
AB  - OBJECTIVE: To determine the reproducibility of the Brodsky grading scale and the
      modified 3-grade and 5-grade scales in reporting the size of the tonsils. DESIGN:
      Retrospective review of 60 video recordings of tonsil examination by 12
      independent observers with different clinical backgrounds and various levels of
      training. The sizes of the tonsils were graded using different grading scales.
      SETTING: Tertiary care university hospital. PARTICIPANTS: The video recordings
      were chosen from an ongoing epidemiologic study of sleep-related breathing
      disorder in children in Hong Kong. Main Outcomes Measures The intraobserver and
      interobserver reproducibility of each grading scale was determined using
      intraclass correlation. An intraclass correlation coefficient (ICC) exceeding
      0.75 was set a priori to indicate an acceptable level of reliability. RESULTS:
      The mean intraobserver ICCs for the Brodsky grading scale and the modified 3
      grade and 5-grade scales were 0.858, 0.830, and 0.865, respectively. The mean
      interobserver ICCs for the Brodsky grading scale and the modified 3-grade and 5
      grade scales were 0.763, 0.739, and 0.783, respectively. CONCLUSION: The Brodsky
      grading scale and the modified 5-grade scale achieved acceptable intraobserver
      and interobserver reproducibility.

PMID- 20157064
TI  - Pediatric primary anterior laryngotracheoplasty: Thyroid ala vs costal cartilage
      grafts.
AB  - OBJECTIVE: To compare outcomes with the use of thyroid ala cartilage (TAC) and
      costal cartilage (CC) grafts in pediatric primary anterior laryngotracheoplasty
      (LTP). DESIGN: Retrospective comparison study. SETTING: Tertiary, academic
      children's hospital. PATIENTS: Of 45 laryngotracheal operations performed between
      June 2001 and October 2008 for laryngotracheal stenosis, 29 were primary anterior
      LTPs. The procedures used either TAC (n = 24) or CC (n = 5) grafts and were
      planned as either single-stage (TAC group, 22 patients; CC group, 2 patients) or
      multistage (TAC group, 2 patients; CC group, 3 patients). MAIN OUTCOME MEASURES:
      Operative time, length of intubation, graft-specific complications, need for
      additional airway procedures, and overall decannulation rate. RESULTS: The mean
      (SD) operative times were 222 (56) minutes for TAC grafts and 363 (59) minutes
      for CC grafts (P = .005). For single-stage LTPs that were decannulated, the mean
      (range) length of intubation was 3.3 (1-11) days for TAC grafts (n = 18) and 3 (1
      5) days for CC grafts (n = 2) (P = .90). Graft-specific complications occurred in
      17% of TAC grafts (n = 4) and 20% of CC grafts (n = 1) (alpha > 0.05).
      Symptomatic stenosis requiring additional surgical intervention occurred in 43%
      of TAC grafts (n = 10) and 60% of CC grafts (n = 3) (alpha > 0.05). Patients
      underwent decannulation in 83% of TAC grafts (n = 19) and 80% of CC grafts (n =
      4) (alpha > 0.05). CONCLUSIONS: In primary anterior LTPs, TAC grafts require
      significantly less operative time than CC grafts (P = .005). There were no
      statistically significant differences in length of intubation, frequency of graft
      specific complications, or decannulation rates between TAC and CC grafts in
      primary anterior LTPs.

PMID- 20157063
TI  - Subglottic stenosis examined as a fibrotic response to airway injury
      characterized by altered mucosal fibroblast activity.
AB  - OBJECTIVE: To investigate the association between mucosal fibroblast activity and
      subglottic stenosis (SGS) development. DESIGN: Prospective study of an animal
      model of SGS. SETTING: Academic research laboratory. SUBJECTS: New Zealand white
      rabbits were assigned to either the cricothyroidotomy and carbon dioxide laser
      injury group or the cricothyroidotomy and silver nitrate injury group. Airways
      were excised for histologic analysis and the establishment of primary fibroblast
      cultures. Lesions from surgical excision of established SGS and subglottic tissue
      were used to analyze SGS recurrence. INTERVENTIONS: The subglottis was approached
      via cricothyroidotomy and was subjected to either carbon dioxide laser or silver
      nitrate injury before closure. The SGS lesions were excised at 8 to 10 weeks and
      were used to establish explants for fibroblast culture. The animals underwent
      recovery for an additional 14 days to follow recurrence of SGS. After 14 days,
      all the animals were killed humanely, and subglottic tissue was harvested for
      histologic evaluation. Rates of migration and contraction of SGS and normal
      airway fibroblasts were assayed using established in vitro methods under basal
      conditions and with prostaglandin E(2) treatment. MAIN OUTCOME MEASURES: For in
      vivo studies, injury, healing, and scarring of the mucosa and cartilage were the
      primary measures. For cultured fibroblast experiments, cellular responses of
      fibroblasts from normal and stenosed mucosa were compared and contrasted.
      RESULTS: Mucosal injury resulted in acute fibroplasia and chronic SGS, surgical
      excision of mature SGS at 8 weeks resulted in rapid recurrence of stenosis, and
      SGS-derived fibroblasts were relatively refractory to the effects of
      prostaglandin E(2) on migration and contraction. CONCLUSIONS: Subglottic stenosis
      represents a fibrotic airway repair process that involves fibroblasts that
      produce recurrent, excessive scar formation. We suggest that SGS development and
      recurrence may be partially dictated by altered fibroblast responsiveness to
      antifibroplastic signals during mucosal repair.

PMID- 20157065
TI  - Update on bone-anchored hearing aids in pediatric patients with profound
      unilateral sensorineural hearing loss.
AB  - OBJECTIVE: To evaluate the use of bone-anchored hearing aids (Bahas) in children
      with single-sided deafness. DESIGN: Retrospective 3-year chart review. SETTING:
      Arkansas Children's Hospital, Little Rock, pediatric hospital serving children
      from birth to 21 years of age. PATIENTS: The study included 23 children (14 girls
      and 9 boys) with single-sided deafness (mean age, 12.6 years; age range, 6-19
      years). INTERVENTIONS: Two-stage Baha surgery with 6-month osseointegration was
      performed on children 5 years and older at a single institution. The Baha
      processor was placed 2 weeks after the second-stage surgery. MAIN OUTCOME
      MEASURES: Results of the Hearing in Noise Test (HINT) and the Children's Home
      Inventory for Listening Difficulties (CHILD) questionnaires were compared before
      and after Baha activation in children with profound unilateral sensorineural
      hearing loss. RESULTS: Preimplant mean HINT scores at speech-noise ratios of 0,
      +5, and +10 dB were 42%, 76%, and 95%, respectively. Postimplant mean HINT scores
      improved to mean speech-noise ratios of 82%, 97%, and 99% at 0, 5, and 10 dB,
      respectively. The CHILD scores also improved from mean preimplant ratings of 4.49
      and 4.60 for patients and parents, respectively, to postimplant ratings of 6.90
      and 7.10. Both teenagers (n = 15) and children younger than 13 years (n = 7)
      demonstrated improved HINT and CHILD scores. The complication rate was 17%.
      CONCLUSION: Bone-anchored hearing aids are a durable treatment option that can
      achieve noticeable improvements in hearing in noise and in listening difficulties
      in children with profound unilateral sensorineural hearing loss.

PMID- 20157066
TI  - Low heritability of tinnitus: results from the second Nord-Trondelag health
      study.
AB  - OBJECTIVE: To estimate the heritability of tinnitus. DESIGN: Self-report
      questionnaire data collected from August 1, 1995, through June 30, 1997, from
      individuals in the Nord-Trondelag Hearing Loss Study (an integrated part of the
      Nord-Trondelag Health Study) were used. The study also included information on
      first-degree family relationships, and age-corrected polychoric correlations of
      relatives' tinnitus status were calculated. A structural equation model was fit
      to the data, and the relative contributions of genes and unique environmental
      effects were estimated. Models that included sex-specific effects were also
      tested. SETTING: Nord-Trondelag County, Norway. PATIENTS: A population-based
      sample of 12 940 spouses, 27 607 parent-offspring, and 11 498 siblings was used.
      A total of 28 066 respondents were tested twice, yielding a test-retest
      correlation of 0.65 for the report of tinnitus. MAIN OUTCOME MEASURE:
      Heritability of tinnitus. RESULTS: Correlations for parent-offspring ranged from
      0.01 to 0.07 for the various sex combinations, sibling correlation ranged from
      0.06 to 0.14, and the spouse correlation was 0.04. This family correlation
      pattern implies an upper limit for heritability of 0.11 with no sex differences
      in the heritability estimates. CONCLUSIONS: This is the first large population
      based family study, to our knowledge, to report on the heritability of tinnitus.
      In contrast to previous speculations in the literature, this low heritability
      indicates that additive genetic effects explain only a small proportion of the
      variance of tinnitus in the population.

PMID- 20157067
TI  - Delayed epistaxis in external dacryocystorhinostomy: rate and risk factors.
AB  - OBJECTIVE: To report the incidence and risk factors associated with delayed
      epistaxis (2-8 days after the procedure) after external dacryocystorhinostomy
      (DCR). DESIGN: We identified and analyzed all cases of patients who underwent
      external DCR procedures at 2 institutions from January 1999 through December
      2005. Cases of delayed epistaxis and their final surgical outcome were compared
      with those without it. SETTING: All patients who underwent surgery and were
      examined at 2 public hospitals in Melbourne, Australia. PATIENTS: A total of 374
      patients who underwent 437 DCRs. INTERVENTIONS: Medical treatment,
      hospitalization, and endonasal examination with cautery. MAIN OUTCOME MEASURES:
      Rate of delayed epistaxis and current and past use of antiplatelet medications.
      RESULTS: Of the 374 patients (mean [SD] age, 62 [18] years; 280 [75%] were women)
      who underwent 437 external DCRs, 15 (3.4%) had an episode of delayed epistaxis.
      They were generally older and more likely to have a history of active
      dacryocystitis compared with those who did not develop delayed epistaxis.
      Preoperative use of aspirin, nonsteroidal anti-inflammatory drugs, or warfarin
      sodium was not associated with delayed epistaxis or poorer surgical outcome if
      these anticoagulants were discontinued preoperatively as instructed. None of the
      15 patients with delayed epistaxis had continued ingesting anticoagulants before
      undergoing DCR. Patients who developed epistaxis (80%) had a significantly lower
      rate of satisfactory surgical outcome than those who did not (90%) (P = .02).
      CONCLUSION: The risk of delayed epistaxis should be similar for patients taking
      or not taking anticoagulant agents if their use is stopped within a defined
      period of time before DCR.

PMID- 20157068
TI  - Association of IL1A, IL1B, and TNF gene polymorphisms with chronic rhinosinusitis
      with and without nasal polyposis: A replication study.
AB  - OBJECTIVE: To replicate and extend recent findings in a Turkish population of
      associations between chronic rhinosinusitis (CRS) with nasal polyposis and single
      nucleotide polymorphisms (SNPs) in the IL1A (rs17561 and Ser114Ala), IL1B
      (rs16944), and TNF (rs361525 and rs1800629) genes. DESIGN: In a case-control
      replication study, DNA samples were obtained from 206 patients with severe CRS
      (cases) and from 196 postal code-matched controls. For IL1A and TNF, the 3
      reported SNPs were complemented with tagging SNPs using an International HapMap
      genotyping data set to ensure complete genetic coverage. For IL1B, only the
      single reported SNP was assessed. A total of 24 SNPs (7 in IL1A, 1 in IL1B, and
      16 in TNF) were individually genotyped. The PLINK software package was used to
      perform genetic association tests. SETTING: Academic research. PATIENTS: Canadian
      population of individuals with severe CRS. MAIN OUTCOME MEASURES: Allelic
      differences between cases and controls. RESULTS: Significant allelic differences
      between cases and controls were obtained for IL1A rs17561 (odds ratio [OR], 1.48;
      P = .02). The following 3 additional SNPs in this gene were associated with CRS:
      rs2856838 (OR, 0.63; P = .003), rs2048874 (OR, 0.57; P = .01), and rs1800587 (OR,
      1.49; P = .02). These 3 SNPs remained significant after correction for multiple
      testing. No association was found with IL1B or TNF. CONCLUSIONS: We replicated
      the previously reported association between the IL1A polymorphism and severe CRS
      and identified 3 potential new associations in the same gene. This further
      supports the potential contribution of IL1A to the development of CRS. We were
      unable to replicate previous reports of associations with IL1B or TNF.

PMID- 20157069
TI  - A case of pyoderma gangrenosum on the nasal dorsum.

PMID- 20157070
TI  - Carotid artery spasm secondary to acute isolated sphenoid sinusitis: implications
      on workup and treatment.

PMID- 20157071
TI  - Radiology quiz case 1. Skull base osseous sarcoidosis.

PMID- 20157072
TI  - Radiology quiz case 2. Gradenigo syndrome caused by right petrous apicitis.

PMID- 20157073
TI  - Pathology quiz case 1. Multifocal oncocytic papillary cystadenoma (OPC).

PMID- 20157074
TI  - Pathology case quiz 2. Diffuse large B-cell lymphoma, T-cell/histiocyte-rich
      morphological variant, of the hard palate.

PMID- 20157075
TI  - Impact of margin status on laser surgery for early glottic cancer.

PMID- 20157076
TI  - Health care reform and comparative effectiveness: implications for surgeons.

PMID- 20157077
TI  - Open letter to young surgeons interested in humanitarian surgery.

PMID- 20157078
TI  - Preventing outbreaks: making our medication delivery system safer.

PMID- 20157079
TI  - Laparoscopic approach for suspected early-stage gallbladder carcinoma.
AB  - OBJECTIVE: To determine the feasibility of the laparoscopic approach for treating
      suspected early-stage gallbladder carcinoma. DESIGN, SETTING, AND PATIENTS:
      Prospective study from a university hospital. From May 10, 2004, to October 9,
      2007, the laparoscopic approach was considered for treating 36 patients with
      suspected gallbladder carcinoma at T2 or less without liver invasion based on the
      preoperative computed tomographic scan. To further exclude liver invasion,
      preoperative endoscopic ultrasonography (US) and laparoscopic US were
      additionally performed. Frozen biopsy was performed after completing the
      cholecystectomy. If carcinoma was found, laparoscopic lymphadenectomy was
      performed. MAIN OUTCOME MEASURES: Feasibility and operative outcome. RESULTS:
      Three patients who had liver invasion on endoscopic US underwent open surgery. An
      additional 3 patients who had liver invasion noted on laparoscopic US had their
      surgical procedure converted to laparotomy. Finally, 30 patients underwent a
      laparoscopic procedure. With combined computed tomography, endoscopic US, and
      laparoscopic US, the negative predictive value for excluding hepatic invasion
      reached 100%. For the 12 patients who had benign lesions noted on their frozen
      biopsies, their laparoscopic surgical procedure was completed. The remaining 18
      patients who had gallbladder carcinoma underwent additional laparoscopic
      lymphadenectomy. During laparoscopic lymphadenectomy 1 conversion occurred owing
      to bleeding, the median operative time was 190 minutes, and the median blood loss
      was 50 mL. The complication rate was 16.7% and the median postoperative hospital
      stay was 4 days. After a median follow-up of 27 months, all 18 patients who
      underwent laparoscopic lymphadenectomy survived without any evidence of
      recurrence or metastasis. CONCLUSION: Laparoscopic treatment is feasible and safe
      in selected patients with early-stage gallbladder carcinoma.

PMID- 20157080
TI  - Predictors of occult nodal metastasis in patients with thin melanoma.
AB  - HYPOTHESIS: Thin primary lesions are largely responsible for the rapid increase
      in melanoma incidence, making identification of appropriate candidates for nodal
      staging in this group critically important. We hypothesized that common clinical
      variables may accurately estimate the risk of nodal metastasis after wide
      excision and determine the need for sentinel node biopsy. DESIGN: Review of
      prospectively acquired data in a large melanoma database. SETTING: A tertiary
      referral center. PATIENTS: A total of 2211 patients with thin melanoma treated by
      wide local excision alone were identified in the database between January 1,
      1971, and December 31, 2005. Of those, 1732 met entry criteria. MAIN OUTCOME
      MEASURES: We examined the rate of regional nodal recurrence and the impact of
      clinical and demographic variables by univariate and multivariate analyses.
      RESULTS: The overall nodal recurrence rate was 2.9%; median time to recurrence
      was 38.3 months. Univariate analysis of 1732 patients identified male sex (P <
      .001), increased Breslow thickness (P < .001), and increased Clark level (P <
      .001) as significant for nodal recurrence. Multivariate analysis identified male
      sex (hazard ratio, 3.5; 95% confidence interval, 1.8-7.0; P < .001), younger age
      (0.45; 0.24-0.86; P = .001), and increased Breslow thickness (2.5; 1.6-3.7;
      categorical P < .001) as significant for nodal recurrence. The Clark level was no
      longer significant (P = .63). Breslow thickness, age, and sex were used to
      develop a scoring system and nomogram for the risk of nodal involvement.
      Predictions ranged from 0.1% in the lowest-risk group to 17.4% in the highest
      risk group. CONCLUSIONS: Many patients with thin melanoma will have nodal
      recurrence after wide excision alone. Three simple clinical variables may be used
      to estimate recurrence risk and select patients for sentinel node biopsy.

PMID- 20157081
TI  - Influence of histamine receptor antagonists on the outcome of perforated
      appendicitis: analysis from a prospective trial.
AB  - HYPOTHESIS: Diphenhydramine blocks the H(1) receptor to treat pruritus or to
      induce sleep, while ranitidine blocks the H(2) receptor to suppress gastric acid.
      They are often given to ill patients, such as those with perforated appendicitis.
      However, these receptors are integral to the inflammatory response, and to our
      knowledge, the impact of H(1) or H(2) blockade on outcome in the setting of
      perforated appendicitis has never been evaluated. DESIGN: Prospective randomized
      trial. SETTING: Referral center. PATIENTS: Children undergoing an operation for
      perforated appendicitis from April 2005 to November 2006. MAIN OUTCOME MEASURES:
      We conducted multivariate analysis with Pearson correlation on data from a
      prospective randomized trial comparing antibiotic regimen after appendectomy for
      perforated appendicitis and outcome. Medications with a significant correlation
      to abscess development were investigated by comparing those receiving the
      medication with those who did not using the t test for continuous variables and
      chi(2) test for discrete variables. Significance was defined as P < or = .05.
      RESULTS: Significant correlations were found between the use of ranitidine (P =
      .05) or diphenhydramine (P = .03) and the development of an abscess. Direct
      comparison found no differences in patient or operative variables in those given
      either medication compared with those receiving no doses. Abscess rate in those
      receiving neither medication (n = 41) was 10%. Those given only ranitidine (n =
      24) or diphenhydramine (n = 17) had doubled abscess rates of 17% and 18%,
      respectively. Those given both medications (n = 16) had a quadrupled abscess rate
      of 44% (P = .03). CONCLUSIONS: Ranitidine or diphenhydramine given to patients
      with perforated appendicitis may increase the risk of postoperative abscess.
      Therefore, these medications should not be used empirically in this population.

PMID- 20157083
TI  - Addressing the Millennium Development Goals from a surgical perspective:
      essential surgery and anesthesia in 8 low- and middle-income countries.
AB  - HYPOTHESIS: Surgical and anesthetic care is increasingly recognized as a
      neglected but cost-effective component of primary health care in low- and middle
      income countries (LMICs). Strengthening delivery can help achieve Millennium
      Development Goals 4, 5, and 6. Large gaps in access to essential surgical care in
      LMICs result in considerable morbidity and mortality. The goal of this study was
      to provide a baseline overview of essential surgical and anesthetic capacity at
      district-level health facilities in multiple LMICs. DESIGN: Survey. SETTING:
      District-level health facilities in multiple LMICs MAIN OUTCOME MEASURES: A
      standardized World Health Organization tool was used at selected district-level
      hospitals to assess infrastructure, supplies, and procedures relating to
      essential surgical and anesthetic capacity. The analysis included facilities from
      countries that assessed more than 5 health facilities. All data were aggregated
      and blinded to avoid intercountry comparisons. RESULTS: Data from 132 facilities
      were analyzed from 8 countries: Democratic Socialist Republic of Sri Lanka (n =
      32), Mongolia (n = 31), United Republic of Tanzania (n = 25), Islamic State of
      Afghanistan (n = 13), Republic of Sierra Leone (n = 11), Republic of Liberia (n =
      9), Republic of The Gambia (n = 6), and Democratic Republic of Sao Tome and
      Principe (n = 5). Universally, facilities demonstrated shortfalls in basic
      infrastructure (water, electricity, oxygen) and functioning anesthesia machines.
      Although 73% of facilities reported performing incision and drainage of
      abscesses, only 48% were capable of undertaking an appendectomy. In line with
      Millennium Development Goals 4, 5, and 6, only 32% of facilities performed
      congenital hernia repairs, 44% of facilities performed cesarean sections, and few
      facilities always had goggles and aprons to protect surgical health care workers
      from human immunodeficiency virus. CONCLUSION: Enormous shortfalls in
      infrastructure, supplies, and procedures undertaken are common at district-level
      health facilities in LMICs.

PMID- 20157082
TI  - Patient characteristics and the occurrence of never events.
AB  - OBJECTIVE: To determine whether the occurrence of "never events" after major
      surgical procedures is affected by patient and disease characteristics and by the
      type of operation performed. DESIGN: Epidemiological analysis. INTERVENTIONS:
      Derivation and assessment of predictive equations for postoperative infectious
      events and decubitus ulcers using Healthcare Cost and Utilization Project
      Nationwide Inpatient Sample administrative claims data for patients hospitalized
      between 2002 and 2005. MAIN OUTCOME MEASURES: C statistics for each predictive
      equation with and without hospital dummy variables. RESULTS: Predictive equations
      for 6 of 8 complications had C statistics greater than 0.65 without hospital
      variables, while 2 had C statistics of less than 0.55. All equations had C
      statistics greater than 0.75 when hospital dummy variables were included.
      CONCLUSIONS: Patient characteristics and type of operative procedure are
      important predictors of complications of surgical care evaluated in this study,
      undermining the rationale for their current classification as "never events."
      Variations in risk-adjusted complication rates among hospitals support the
      influence of quality of care on their occurrence. Development and use of
      warranties to cover costs associated with caring for the unavoidable components
      of potentially avoidable complications is proposed as a means of rewarding high
      quality providers without creating unrealistic expectations or perverse financial
      incentives.

PMID- 20157084
TI  - Underuse of axillary dissection for the management of sentinel node
      micrometastases in breast cancer.
AB  - BACKGROUND: Current American Society of Clinical Oncology guidelines for
      management of sentinel node micrometastases (SNMM) in breast cancer recommend
      axillary lymph node dissection (ALND) for all patients. OBJECTIVE: To assess
      nationwide use of ALND for SNMM. DESIGN: Population-based retrospective
      observational study. SETTING: The National Cancer Institute's Surveillance,
      Epidemiology, and End Results database (1998-2005). PATIENTS: Five thousand three
      hundred fifty-three patients with SNMM. MAIN OUTCOME MEASURE: Use of ALND after
      identification of SNMM. RESULTS: The prevalence of SNMM increased from 2.5% in
      1998 to 17.7% in 2005. Of 5353 patients with SNMM, 2160 (40.4%) had no further
      nodal surgery and 3193 (59.6%) underwent ALND. In the latter group,
      histopathologic examination of nonsentinel nodes upstaged 18.6% of cases to N1,
      2.2% to N2, and 0.1% to N3 disease. Multivariate analysis using logistic
      regression showed that age younger than 66 years (odds ratio [OR], 1.79; 95%
      confidence interval [CI], 1.56-2.04), high tumor grade (OR, 1.22; 95% CI, 1.07-
      1.40), and tumor size larger than 2 cm (OR, 1.16; 95% CI, 1.01-1.32) were
      predictive of ALND. Predictors of upstaging were infiltrating lobular histology
      (OR, 1.23; 95% CI, 1.00-1.51), T2 stage (OR, 1.38; 95% CI, 1.14-1.67), T3 stage
      (OR, 3.66; 95% CI, 1.70-7.90), and number of nodes examined (OR, 1.04; 95% CI,
      1.03-1.05). CONCLUSIONS: Only 60% of patients with SNMM from breast cancer are
      treated according to American Society of Clinical Oncology guidelines. Nodal
      staging based only on sentinel node biopsy may underestimate the extent of nodal
      disease in 20.9% of cases. Surgical management of SNMM should be standardized.

PMID- 20157086
TI  - Revisional bariatric surgery: 13-year experience from a tertiary institution.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of revisional bariatric
      surgery at a tertiary institution. Revisional bariatric operations for
      unsuccessful weight loss or intolerable complications following the primary
      intervention are increasing. DESIGN: Case series from a prospective database.
      SETTING: Tertiary bariatric referral center. PATIENTS: From 1995 to 2008, 56
      patients who had been formerly operated on for clinically severe obesity
      underwent a revisional procedure at our institution. Their mean (SD) age and body
      mass index were 39.6 (9.6) years and 46.9 (16.4), respectively. They were divided
      into 3 groups according to the indications for reoperation: (1) unsatisfactory
      weight loss (n = 39), (2) severe nutritional complications (n = 15), and (3)
      intolerable adverse effects (n = 2). MAIN OUTCOME MEASURES: Effectiveness of the
      procedures according to the indication of revision and overall morbidity and
      mortality rates. RESULTS: Mean (SD) follow-up was 102 (8) months. There was no
      mortality but there was an early morbidity rate of 33.9% due to postoperative
      complications, including 2 cases of acute renal failure (3.6%), 5 anastomotic
      leaks (13.1%), 8 cases of pneumonia (14.3%), and 1 case each of wound infection,
      incisional dehiscence, bile leak, and small-bowel obstruction (1.8%). Late
      complications included stenosis of the gastrojejunal anastomosis in 2 patients
      (3.6%), hypoalbuminemia in 2 patients (3.6%), and incisional herniation in 9
      patients (16.1%). Late morbidity was 23.2%. CONCLUSION: Although revisional
      bariatric surgery is associated with higher risk of perioperative complications
      compared with the primary procedures, it appears to be safe and effective when
      performed in experienced centers.

PMID- 20157085
TI  - Pancreatoduodenectomy for ductal adenocarcinoma: implications of positive margin
      on survival.
AB  - OBJECTIVE: To assess the effect of R0 resection margin status and R0 en bloc
      resection in pancreatoduodenectomy outcomes. DESIGN: Retrospective medical record
      review. SETTING: Mayo Clinic, Rochester, Minnesota. PATIENTS: Patients who
      underwent pancreatoduodenectomy for pancreatic adenocarcinoma at our institution
      between January 1, 1981, and December 31, 2007, were identified and their medical
      records were reviewed. MAIN OUTCOME MEASURE: Median survival times. RESULTS: A
      total of 617 patients underwent pancreatoduodenectomy. Median survival times
      after R0 en bloc resection (n = 411), R0 non-en bloc resection (n = 57), R1
      resection (n = 127), and R2 resection (n = 22) were 19, 18, 15, and 10 months,
      respectively (P < .001). A positive resection margin was associated with death (P
      = .01). No difference in survival time was found between patients undergoing R0
      en bloc and R0 resections after reexcision of an initial positive margin (hazard
      ratio, 1.19; 95% confidence interval, 0.87-1.64; P = .28). CONCLUSIONS: R0
      resection remains an important prognostic factor. Achieving R0 status by initial
      en bloc resection or reexcision results in similar long-term survival.

PMID- 20157087
TI  - Racial and ethnic differences in the use of high-volume hospitals and surgeons.
AB  - OBJECTIVE: To examine racial/ethnic differences in the use of high-volume
      hospitals and surgeons for 10 surgical procedures with documented associations
      between volume and mortality. DESIGN: Cross-sectional regression analysis.
      SETTING: New York City area hospital discharge data, 2001-2004. PATIENTS: Adults
      from 4 racial/ethnic categories (white, black, Asian, and Hispanic) who underwent
      surgery for cancer (breast, colorectal, gastric, lung, or pancreatic resection),
      cardiovascular disease (coronary artery bypass graft, coronary angioplasty,
      abdominal aortic aneurysm repair, or carotid endarterectomy), or orthopedic
      conditions (total hip replacement). MAIN OUTCOME MEASURE: Treatment by a high
      volume surgeon at a high-volume hospital. RESULTS: There were 133 821 patients
      who underwent 1 of the 10 procedures. For 9 of the 10 procedures, black patients
      were significantly (P < .05) less likely (after adjustment for sociodemographic
      characteristics, insurance type, proximity to high-volume providers, and
      comorbidities) to be operated on by a high-volume surgeon at a high-volume
      hospital and more likely to be operated on by a low-volume surgeon at a low
      volume hospital. Asian and Hispanic patients, respectively, were significantly
      less likely to use high-volume surgeons at high-volume hospitals for 5 and 4 of
      the 10 procedures and more likely to use low-volume surgeons at low-volume
      hospitals for 3 and 5 of the 10 procedures. CONCLUSIONS: Minority patients in New
      York City are doubly disadvantaged in their surgical care; they are substantially
      less likely to use both high-volume hospitals and surgeons for procedures with an
      established volume-mortality association. Better information is needed about
      which providers minority patients have access to and how they select them.

PMID- 20157088
TI  - Translational research in surgical disease.
AB  - OBJECTIVE: To review cutting-edge, novel, implemented and potential translational
      research and to provide a glimpse into rich, innovative, and brilliant approaches
      to everyday surgical problems. DATA SOURCES: Scientific literature and
      unpublished results. STUDY SELECTION: Articles reviewed were chosen based on
      innovation and application to surgical diseases. DATA EXTRACTION: Each section
      was written by a surgeon familiar with cutting-edge and novel research in their
      field of expertise and interest. DATA SYNTHESIS: Articles that met criteria were
      summarized in the manuscript. CONCLUSIONS: Multiple avenues have been used for
      the discovery of improved means of diagnosis, treatment, and overall management
      of patients with surgical diseases. These avenues have incorporated the use of
      genomics, electrical impedence, statistical and mathematical modeling, and
      immunology.

PMID- 20157089
TI  - A unified approach to validation, reliability, and education study design for
      surgical technical skills training.
AB  - OBJECTIVE: To present modern educational psychology theory and apply these
      concepts to validity and reliability of surgical skills training and assessment.
      DESIGN: In a series of cross-disciplinary meetings, we applied a unified approach
      of behavioral science principles and theory to medical technical skills education
      given the recent advances in the theories in the field of behavioral psychology
      and statistics. CONCLUSIONS: While validation of the individual simulation tools
      is important, it is only one piece of a multimodal curriculum that in and of
      itself deserves examination and study. We propose concurrent validation
      throughout the design of simulation-based curriculum rather than once it is
      complete. We embrace the concept that validity and curriculum development are
      interdependent, ongoing processes that are never truly complete. Individual
      predictive, construct, content, and face validity aspects should not be
      considered separately but as interdependent and complementary toward an end
      application. Such an approach could help guide our acceptance and appropriate
      application of these exciting new training and assessment tools for technical
      skills training in medicine.

PMID- 20157090
TI  - Hemorrhagic cholecystitis.
AB  - Hemorrhagic cholecystitis is a rare cause of abdominal pain that can present in
      the setting of trauma, malignancy, and bleeding diathesis, such as renal failure,
      cirrhosis, and anticoagulation. Its symptoms are easily confused with acute
      calculous cholecystitis and might include hemobilia or hematemesis as blood
      drains from the gallbladder into the gastrointestinal tract. Imaging of
      hemorrhagic cholecystitis can be misleading unless the possibility of this
      diagnosis is considered. In this report, we present 2 cases of hemorrhagic
      cholecystitis along with relevant imaging and a review of the literature on this
      rare subject.

PMID- 20157091
TI  - Image of the month. Sclerosing angiomatoid nodular transformation of the spleen.

PMID- 20157092
TI  - Image of the month. Inflammatory breast carcinoma.

PMID- 20157093
TI  - Blunt needles for patients' and surgeons' safety.

PMID- 20157094
TI  - Women in surgery.

PMID- 20157095
TI  - Routine postoperative gastrografin studies are not necessary after laparoscopic
      gastric banding.

PMID- 20157097
TI  - The background review for the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157096
TI  - Longitudinal study of human papillomavirus persistence and cervical
      intraepithelial neoplasia grade 2/3: critical role of duration of infection.
AB  - BACKGROUND: The natural history of human papillomavirus (HPV) infections in older
      women is critical for preventive strategies, including vaccination and screening
      intervals, but is poorly understood. In a 7-year population-based cohort study in
      Guanacaste, Costa Rica, we examined whether women's age and the duration of
      carcinogenic HPV infections influenced subsequent persistence of infection and
      risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease.
      METHODS: At enrollment, of the 9466 participants eligible for pelvic examination,
      9175 were screened for cervical neoplasia using multiple methods; those with CIN
      2 or worse disease were censored and treated. Participants at low risk of CIN 2
      or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas
      higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and
      initially sexually inactive women (n = 410) were rescreened annually or
      semiannually (actively followed) for up to 7 years. HPV testing was done using a
      polymerase chain reaction-based method. We determined, by four age groups (18-25,
      26-33, 34-41, and > or =42 years), the proportion of prevalent infections (found
      at baseline) and newly detected infections (first found during follow-up) that
      persisted at successive 1-year time points and calculated absolute risks of CIN 2
      and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided.
      RESULTS: Regardless of the woman's age, newly detected infections were associated
      with very low absolute risks of persistence, CIN 2, or worse disease. For newly
      detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years
      of follow-up, was not higher for women aged 34 years and older than for younger
      women. Moreover, rates of newly detected infections declined sharply with age (in
      the actively followed group, at ages 18-25, 26-33, 34-41, and > or =42 years,
      rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among
      prevalent infections, persistent infections among older women (> or =42 years)
      was higher than that among younger age groups or new infections at any age (P <
      .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected
      during follow-up was associated with prevalent infections. Only a small subset
      (25 of 1128) of prevalent infections persisted throughout follow-up without
      apparent CIN 2 or worse. CONCLUSIONS: The rate of new infections declines with
      age, and new infections typically do not progress to CIN 2 or worse disease in
      older women; thus, overall potential benefit of prophylactic vaccination or
      frequent HPV screening to prevent or detect new carcinogenic HPV infections at
      older ages is low.

PMID- 20157098
TI  - Comments and response on the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157099
TI  - When evidence collides with anecdote, politics, and emotion: breast cancer
      screening.

PMID- 20157100
TI  - Comments and response on the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157101
TI  - Comments and response on the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157102
TI  - Comments and response on the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157104
TI  - Comments and response on the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157105
TI  - Comments and response on the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157106
TI  - Editors' note on the USPSTF recommendation on screening for breast cancer.

PMID- 20157107
TI  - Comments and response on the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157108
TI  - Comments and response on the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157109
TI  - The background review for the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157111
TI  - The background review for the USPSTF recommendation on screening for breast
      cancer.

PMID- 20157112
TI  - Coordinate down-regulation of adenylyl cyclase isoforms and the stimulatory G
      protein (G(s)) in intestinal epithelial cell differentiation.
AB  - The intestinal epithelium is dynamic, with proliferation of undifferentiated
      crypt cells balanced by terminal differentiation and cell death at the colon
      surface or small intestinal villus tips. Cyclic AMP, induced by agonists such as
      prostaglandin E(2) and vasoactive intestinal polypeptide, promotes proliferation
      and ion secretion and suppresses apoptosis in intestinal epithelial cells. Here,
      we show that cell differentiation in a model intestinal epithelium leads to
      attenuation of cAMP production in response to G protein-coupled receptor and
      receptor-independent agonists. Concomitantly, key components of the cAMP cascade,
      the alpha subunit of the stimulatory G protein, G(s), and adenylyl cyclase (AC)
      isoforms 3, 4, 6, and 7 are down-regulated. By contrast, AC1, AC2, AC8, and AC9,
      and the receptors for prostaglandin E(2) and vasoactive intestinal polypeptide,
      are not expressed or not affected by differentiation. We confirmed key findings
      in normal murine colon epithelium, in which the major AC isoforms and G(s)alpha
      are markedly down-regulated in differentiated surface cells. Suppression of AC
      isoforms and G(s)alpha is functionally important, because their constitutive
      expression completely reverses differentiation-induced cAMP attenuation. Thus,
      down-regulation of AC isoforms and G(s)alpha is an integral part of the
      intestinal epithelial differentiation program, perhaps serving to release cells
      from cAMP-promoted anti-apoptosis as a prerequisite for cell death upon terminal
      differentiation.

PMID- 20157113
TI  - Dynamic regulation of a metabolic multi-enzyme complex by protein kinase CK2.
AB  - The reversible association and dissociation of a metabolic multi-enzyme complex
      participating in de novo purine biosynthesis, the purinosome, was demonstrated in
      live cells to respond to the levels of purine nucleotides in the culture media.
      We also took advantage of in vitro proteomic scale studies of cellular substrates
      of human protein kinases (e.g. casein kinase II (CK2) and Akt), that implicated
      several de novo purine biosynthetic enzymes as kinase substrates. Here, we
      successfully identified that purinosome formation in vivo was significantly
      promoted in HeLa cells by the addition of small-molecule CK2-specific inhibitors
      (i.e. 4,5,6,7-tetrabromo-1H-benzimidazole, 2-dimethylamino-4,5,6,7-tetrabromo-1H
      benzimidazole, tetrabromocinammic acid, 4,4',5,5',6,6'-hexahydroxydiphenic acid
      2,2',6,6'-dilactone (ellagic acid) as well as by silencing the endogenous human
      CK2alpha catalytic subunit with small interfering RNA. However, 4,5,6,7
      tetrabromobenzotriazole, another CK2-specific inhibitor, triggered the
      dissociation of purinosome clusters in HeLa cells. Although the mechanism by
      which 4,5,6,7-tetrabromobenzotriazole affects purinosome clustering is not clear,
      we were capable of chemically reversing purinosome formation in cells by the
      sequential addition of two CK2 inhibitors. Collectively, we provide compelling
      cellular evidence that CK2-mediated pathways reversibly regulate purinosome
      assembly, and thus the purinosome may be one of the ultimate targets of kinase
      inhibitors.

PMID- 20157114
TI  - A structural determinant that renders G alpha(i) sensitive to activation by
      GIV/girdin is required to promote cell migration.
AB  - Although several non-receptor activators of heterotrimeric G proteins have been
      identified, the structural features of G proteins that determine their
      interaction with such activators and the subsequent biological effects are poorly
      understood. Here we investigated the structural determinants in G alpha(i3)
      necessary for its regulation by GIV/girdin, a guanine-nucleotide exchange factor
      (GEF) that activates G alpha(i) subunits. Using G protein activity and in vitro
      pulldown assays we demonstrate that G alpha(i3) is a better substrate for GIV
      than the highly homologous G alpha(o). We identified Trp-258 in the G alpha(i)
      subunit as a novel structural determinant for GIV binding by comparing GIV
      binding to G alpha(i3)/G alpha(o) chimeras. Mutation of Trp-258 to the
      corresponding Phe in G alpha(o) decreased GIV binding in vitro and in cultured
      cells but did not perturb interaction with other G alpha-binding partners, i.e. G
      betagamma, AGS3 (a guanine nucleotide dissociation inhibitor), GAIP/RGS19 (a
      GTPase-activating protein), and LPAR1 (a G protein-coupled receptor). Activation
      of G alpha(i3) by GIV was also dramatically reduced when Trp-258 was replaced
      with Tyr, Leu, Ser, His, Asp, or Ala, highlighting that Trp is required for
      maximal activation. Moreover, when mutant G alpha(i3) W258F was expressed in HeLa
      cells they failed to undergo cell migration and to enhance Akt signaling after
      growth factor or G protein-coupled receptor stimulation. Thus activation of G
      alpha(i3) by GIV is essential for biological functions associated with G
      alpha(i3) activation. In conclusion, we have discovered a novel structural
      determinant on G alpha(i) that plays a key role in defining the selectivity and
      efficiency of the GEF activity of GIV on G alpha(i) and that represents an
      attractive target site for designing small molecules to disrupt the G alpha(i)
      GIV interface for therapeutic purposes.

PMID- 20157115
TI  - Down-regulation of protein-tyrosine phosphatases activates an immune receptor in
      the absence of its translocation into lipid rafts.
AB  - The earliest known biochemical step that occurs after ligand binding to the
      multichain immune recognition receptor is tyrosine phosphorylation of the
      receptor subunits. In mast cells and basophils activated by multivalent antigen
      IgE complexes, this step is mediated by Src family kinase Lyn, which
      phosphorylates the high affinity IgE receptor (Fc epsilonRI). However, the exact
      molecular mechanism of this phosphorylation step is incompletely understood. In
      this study, we tested the hypothesis that changes in activity and/or topography
      of protein-tyrosine phosphatases (PTPs) could play a major role in the Fc
      epsilonRI triggering. We found that exposure of rat basophilic leukemia cells or
      mouse bone marrow-derived mast cells to PTP inhibitors, H(2)O(2) or pervanadate,
      induced phosphorylation of the Fc epsilonRI subunits, similarly as Fc epsilonRI
      triggering. Interestingly, and in sharp contrast to antigen-induced activation,
      neither H(2)O(2) nor pervanadate induced any changes in the association of Fc
      epsilonRI with detergent-resistant membranes and in the topography of Fc
      epsilonRI detectable by electron microscopy on isolated plasma membrane sheets.
      In cells stimulated with pervanadate, H(2)O(2) or antigen, enhanced oxidation of
      active site cysteine of several PTPs was detected. Unexpectedly, most of oxidized
      phosphatases bound to the plasma membrane were associated with the actin
      cytoskeleton. Several PTPs (SHP-1, SHP-2, hematopoietic PTP, and PTP-MEG2) showed
      changes in their enzymatic activity and/or oxidation state during activation.
      Based on these and other data, we propose that down-regulation of enzymatic
      activity of PTPs and/or changes in their accessibility to the substrates play a
      key role in initial tyrosine phosphorylation of the Fc epsilonRI and other
      multichain immune receptors.

PMID- 20157116
TI  - A new arylsulfate sulfotransferase involved in liponucleoside antibiotic
      biosynthesis in streptomycetes.
AB  - Sulfotransferases are involved in a variety of physiological processes and
      typically use 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as the sulfate donor
      substrate. In contrast, microbial arylsulfate sulfotransferases (ASSTs) are PAPS
      independent and utilize arylsulfates as sulfate donors. Yet, their genuine
      acceptor substrates are unknown. In this study we demonstrate that Cpz4 from
      Streptomyces sp. MK730-62F2 is an ASST-type sulfotransferase responsible for the
      formation of sulfated liponucleoside antibiotics. Gene deletion mutants showed
      that cpz4 is required for the production of sulfated caprazamycin derivatives.
      Cloning, overproduction, and purification of Cpz4 resulted in a 58-kDa soluble
      protein. The enzyme catalyzed the transfer of a sulfate group from p-nitrophenol
      sulfate (K(m) 48.1 microM, k(cat) 0.14 s(-1)) and methyl umbelliferone sulfate
      (K(m) 34.5 microM, k(cat) 0.15 s(-1)) onto phenol (K(m) 25.9 and 29.7 mM,
      respectively). The Cpz4 reaction proceeds by a ping pong bi-bi mechanism. Several
      structural analogs of intermediates of the caprazamycin biosynthetic pathway were
      synthesized and tested as substrates of Cpz4. Des-N-methyl-acyl-caprazol was
      converted with highest efficiency 100 times faster than phenol. The fatty acyl
      side chain and the uridyl moiety seem to be important for substrate recognition
      by Cpz4. Liponucleosides, partially purified from various mutant strains, were
      readily sulfated by Cpz4 using p-nitrophenol sulfate. No product formation could
      be observed with PAPS as the donor substrate. Sequence homology of Cpz4 to the
      previously examined ASSTs is low. However, numerous orthologs are encoded in
      microbial genomes and represent interesting subjects for future investigations.

PMID- 20157117
TI  - Widespread genomic instability mediated by a pathway involving glycoprotein Ib
      alpha and Aurora B kinase.
AB  - c-Myc (Myc) oncoprotein induction of genomic instability (GI) contributes to its
      initial transforming function and subsequent tumor cell evolution. We describe
      here a pathway by which Myc, via its target protein glycoprotein Ibalpha (GpIb
      alpha), mediates GI. Proteomic profiling revealed that the serine/threonine
      kinase Aurora B is down-regulated by GpIb alpha in p53-deficient primary human
      fibroblasts. The phenotypes of Aurora B deficiency are strikingly reminiscent of
      Myc or GpIb alpha overexpression and include double-stranded DNA breaks, altered
      nuclear size and morphology, chromatin bridges, cleavage furrow regression, and
      tetraploidy. During mitosis, GpIb alpha and Aurora B redistribute to the cleavage
      furrow along with other cleavage furrow proteins. GpIb alpha overexpression at
      levels comparable with those seen in some tumor cells causes the dispersal of
      these proteins but not Aurora B, resulting in furrow regression and cytokinesis
      failure. Aurora B normalization redirects the mislocalized furrow proteins to
      their proper location, corrects the cleavage furrow abnormalities, and restores
      genomic stability. Aurora B thus appears necessary for a previously unrecognized
      function in guiding and positioning a number of key proteins, including GpIb
      alpha to the cleavage furrow. These findings underscore the importance of
      maintaining a delicate balance among cleavage furrow-associated proteins during
      mitosis. Suppression of Aurora B via GpIb alpha provides a unifying and
      mechanistic explanation for several types of Myc-mediated GI.

PMID- 20157119
TI  - Summaries for patients: Pipe and cigar smoking and lung function.

PMID- 20157120
TI  - Summaries for patients: The effect of estrogen plus progestin on coronary heart
      disease.

PMID- 20157118
TI  - Selenium compounds activate early barriers of tumorigenesis.
AB  - Selenium chemoprevention by apoptosis has been well studied, but it is not clear
      whether selenium can activate early barriers of tumorigenesis, namely senescence
      and DNA damage response. To test this hypothesis, we treated normal and cancerous
      cells with a gradient concentration of sodium selenite, methylseleninic acid and
      methylselenocysteine for 48 h, followed by a recovery of 1-7 days. Here we show
      that selenium compounds at doses of </=LD(50) can induce cellular senescence, as
      evidenced by the expression of senescence-associated beta-galactosidase and 5
      bromo-2-deoxyuridine incorporation, in normal but not cancerous cells. In
      response to clastogens, the ataxia telangiectasia mutated (ATM) protein is
      rapidly activated, which in turn initiates a cascade of DNA damage response. We
      found that the ATM pathway is activated by the selenium compounds, and the kinase
      activity is required for the selenium-induced senescence response. Pretreatment
      of the MRC-5 non-cancerous cells with the antioxidant N-acetylcysteine or 2,2,6,6
      tetramethylpiperidine-1-oxyl suppresses the selenium-induced ATM activation and
      senescence. Taken together, the results suggest a novel role of selenium in the
      activation of early tumorigenesis barriers specific in non-cancerous cells,
      whereby selenium induces an ATM-dependent senescence response that depends on
      reactive oxygen species.

PMID- 20157121
TI  - Summaries for patients: Observations of the relationship between surface and deep
      leg blood vein clotting.

PMID- 20157122
TI  - ACP Journal Club. Review: Adding antiviral drugs to steroids did not improve
      facial muscle recovery in Bell palsy.

PMID- 20157123
TI  - ACP Journal Club. Review: Neuraminidase inhibitors relieve influenza symptoms and
      reduce laboratory-confirmed influenza in healthy adults.

PMID- 20157124
TI  - ACP Journal Club. Either cholesterol or apolipoprotein levels can be used to
      determine risk for CVD; triglycerides are not useful.

PMID- 20157125
TI  - ACP Journal Club. Pioglitazone was associated with lower risk for adverse
      cardiovascular events than rosiglitazone in older patients.

PMID- 20157126
TI  - ACP Journal Club. Review: therapeutic hypothermia improves neurologic outcome and
      survival to discharge after cardiac arrest.

PMID- 20157127
TI  - ACP Journal Club. Review: Early treatment of a cardiovascular event with nitrates
      or ACE inhibitors reduces short-term mortality.

PMID- 20157128
TI  - ACP Journal Club. Noninvasive ventilation after extubation reduced respiratory
      failure and 90-day mortality in hypercapnic patients.

PMID- 20157129
TI  - ACP Journal Club. Higher-intensity continuous renal-replacement therapy did not
      reduce mortality in critically ill patients with kidney injury.

PMID- 20157130
TI  - ACP Journal Club. Adding revascularization to medical therapy did not improve
      renal function in atherosclerotic renal artery stenosis.

PMID- 20157131
TI  - ACP Journal Club. Review: In women 39 to 69 years of age, screening with
      mammography reduces breast cancer mortality.

PMID- 20157132
TI  - ACP Journal Club. Estrogen plus progestin increased lung cancer mortality but not
      incidence in postmenopausal women.

PMID- 20157133
TI  - ACP Journal Club. A cervical collar or physiotherapy was better than a wait-and
      see policy for early pain relief in cervical radiculopathy.

PMID- 20157134
TI  - The association of pipe and cigar use with cotinine levels, lung function, and
      airflow obstruction: a cross-sectional study.
AB  - BACKGROUND: Cigarette smoking is the major cause of chronic obstructive pulmonary
      disease, but studies on the contribution of other smoking techniques are sparse.
      OBJECTIVE: To determine whether pipe and cigar smoking was associated with
      elevated cotinine levels, decrements in lung function, and increased odds of
      airflow obstruction. DESIGN: Cross-sectional study. SETTING: Population-based
      sample from 6 U.S. communities. PARTICIPANTS: Men and women aged 48 to 90 years
      without clinical cardiovascular disease at enrollment who were part of MESA
      (Multi-Ethnic Study of Atherosclerosis). MEASUREMENTS: The MESA Lung Study
      measured spirometry according to American Thoracic Society guidelines and urine
      cotinine levels by immunoassay on a subsample of MESA. Pipe-years and cigar-years
      were calculated as years from self-reported age of starting to age of quitting
      (or to current age in current users) multiplied by pipe-bowls or cigars per day.
      RESULTS: Of 3528 participants, 9% reported pipe smoking (median, 15 pipe-years),
      11% reported cigar smoking (median, 6 cigar-years), and 52% reported cigarette
      smoking (median, 18 pack-years). Self-reported current pipe and cigar smokers had
      elevated urine cotinine levels compared with never-smokers. Pipe-years were
      associated with decrements in FEV(1), and cigar-years were associated with
      decrements in the FEV(1)-FVC ratio. Participants who smoked pipes or cigars had
      increased odds of airflow obstruction whether they had also smoked cigarettes
      (odds ratio, 3.43 [95% CI, 1.75 to 6.71]; P < 0.001) or not (odds ratio, 2.31
      [CI, 1.04 to 5.11]; P = 0.039) compared with participants with no smoking
      history. LIMITATION: Cross-sectional design. CONCLUSION: Pipe and cigar smoking
      increased urine cotinine levels and was associated with decreased lung function
      and increased odds of airflow obstruction, even in participants who had never
      smoked cigarettes. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood
      Institute, National Institutes of Health.

PMID- 20157135
TI  - Coronary heart disease in postmenopausal recipients of estrogen plus progestin
      therapy: does the increased risk ever disappear? A randomized trial.
AB  - BACKGROUND: Estrogen plus progestin therapy increases the risk for coronary heart
      disease (CHD) in postmenopausal women. However, this increased risk might be
      limited to the first years of use and to women who start therapy late in
      menopause. OBJECTIVE: To estimate the effect of continuous estrogen plus
      progestin therapy on CHD risk over time and stratified by years since menopause.
      DESIGN: Women's Health Initiative randomized, double-blinded, placebo-controlled
      trial. (ClinicalTrials.gov registration number: NCT00000611) SETTING: 40 U.S.
      clinical centers. PATIENTS: 16 608 postmenopausal women with an intact uterus at
      baseline from 1993 to 1998. INTERVENTION: Conjugated equine estrogens, 0.625
      mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo. MEASUREMENTS:
      Adherence-adjusted hazard ratios and CHD-free survival curves estimated through
      inverse probability weighting. RESULTS: Compared with no use of hormone therapy,
      the hazard ratio for continuous use of estrogen plus progestin therapy was 2.36
      (95% CI, 1.55 to 3.62) for the first 2 years and 1.69 (CI, 0.98 to 2.89) for the
      first 8 years. For women within 10 years after menopause, the hazard ratios were
      1.29 (CI, 0.52 to 3.18) for the first 2 years and 0.64 (CI, 0.21 to 1.99) for the
      first 8 years, and the CHD-free survival curves for continuous use and no use of
      estrogen plus progestin crossed at about 6 years (CI, 2 years to 10 years).
      LIMITATION: The analysis may not have fully adjusted for joint determinants of
      adherence and CHD risk. Sample sizes for some subgroup analyses were small.
      CONCLUSION: No suggestion of a decreased risk for CHD was found within the first
      2 years of estrogen plus progestin use, including in women who initiated therapy
      within 10 years after menopause. A possible cardioprotective effect in these
      women who initiated therapy closer to menopause became apparent only after 6
      years of use. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

PMID- 20157137
TI  - Frequency of inappropriate medical exceptions to quality measures.
AB  - BACKGROUND: Quality improvement programs that allow physicians to document
      medical reasons for deviating from guidelines preserve clinicians' judgment while
      enabling them to strive for high performance. However, physician misconceptions
      or gaming potentially limit programs. OBJECTIVE: To implement computerized
      decision support with mechanisms to document medical exceptions to quality
      measures and to perform peer review of exceptions and provide feedback when
      appropriate. DESIGN: Observational study. SETTING: Large internal medicine
      practice. PARTICIPANTS: Patients eligible for 1 or more quality measures.
      MEASUREMENTS: A peer-review panel judged medical exceptions to 16 chronic disease
      and prevention quality measures as appropriate, inappropriate, or of uncertain
      appropriateness. Medical records were reviewed after feedback was given to
      determine whether care changed. RESULTS: Physicians recorded 650 standardized
      medical exceptions during 7 months. The reporting tool was used without any
      medical reason 36 times (5.5%). Of the remaining 614 exceptions, 93.6% were
      medically appropriate, 3.1% were inappropriate, and 3.3% were of uncertain
      appropriateness. Frequencies of inappropriate exceptions were 7 (6.9%) for
      coronary heart disease, 0 (0%) for heart failure, 10 (10.8%) for diabetes, and 2
      (0.6%) for preventive services. After physicians received direct feedback about
      inappropriate exceptions, 8 of 19 (42%) changed management. The peer-review
      process took less than 5 minutes per case, but for each change in clinical care,
      65 reviews were required. LIMITATION: The findings could differ at other sites or
      if financial incentives were in place. CONCLUSION: Physician-recorded medical
      exceptions were correct most of the time. Peer review of medical exceptions can
      identify myths and misconceptions, but the process needs to be more efficient to
      be sustainable. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and
      Quality.

PMID- 20157136
TI  - Superficial venous thrombosis and venous thromboembolism: a large, prospective
      epidemiologic study.
AB  - BACKGROUND: Superficial venous thrombosis (SVT) is perceived to have a benign
      prognosis. OBJECTIVE: To assess the prevalence of venous thromboembolism in
      patients with SVT and to determine the 3-month incidence of thromboembolic
      complications. DESIGN: National cross-sectional and prospective epidemiologic
      cohort study. (ClinicalTrials.gov registration number: NCT00818688) SETTING:
      French office- and hospital-based vascular medicine specialists. PATIENTS: 844
      consecutive patients with symptomatic SVT of the lower limbs that was at least 5
      cm on compression ultrasonography. MEASUREMENTS: Incidence of venous
      thromboembolism and extension or recurrence of SVT in patients with isolated SVT
      at presentation. RESULTS: Among 844 patients with SVT at inclusion (median age,
      65 years; 547 women), 210 (24.9%) also had deep venous thrombosis (DVT) or
      symptomatic pulmonary embolism. Among 600 patients without DVT or pulmonary
      embolism at inclusion who were eligible for 3-month follow-up, 58 (10.2%)
      developed thromboembolic complications at 3 months (pulmonary embolism, 3 [0.5%];
      DVT, 15 [2.8%]; extension of SVT, 18 [3.3%]; and recurrence of SVT, 10 [1.9%]),
      despite 540 patients (90.5%) having received anticoagulants. Risk factors for
      complications at 3 months were male sex, history of DVT or pulmonary embolism,
      previous cancer, and absence of varicose veins. LIMITATION: The findings are from
      a specialist referral setting, and the study was terminated before the target
      patient population was reached because of slow recruitment. CONCLUSION: A
      substantial number of patients with SVT exhibit venous thromboembolism at
      presentation, and some that do not can develop this complication in the
      subsequent 3 months. PRIMARY FUNDING SOURCE: GlaxoSmithKline, sanofi-aventis, and
      the Ministere Francais de la Sante et des Sports (Programme Hospitalier de
      Recherche Clinique).

PMID- 20157138
TI  - Narrative review: the role of Th2 immune pathway modulation in the treatment of
      severe asthma and its phenotypes.
AB  - New therapeutic approaches are needed for patients with severe asthma who are
      refractory to standard therapy comprising high doses of inhaled corticosteroids
      plus long-acting beta(2)-agonists. Current treatment guidelines for patients with
      severe asthma from the National Asthma Education and Prevention Program recommend
      the addition of oral corticosteroids, which are associated with substantial
      morbidity, and, for those with allergic asthma, anti-IgE. Genetic and
      translational studies, as well as clinical trials, suggest that in a subgroup of
      patients, the pathobiology of severe asthma is mediated by immune pathways driven
      by T-helper 2 (Th2)-type CD4(+) T cells, which produce a characteristic
      repertoire of interleukins (ILs), including IL-4, IL-5, and IL-13. Therefore,
      biological modifiers of Th2-type ILs, such as monoclonal antibodies, soluble
      receptors, and receptor antagonists, are a rational strategy for developing new
      treatment approaches but will need to be targeted to selected patients in whom
      the appropriate Th2 immune pathway is "active." The benefits of immune-modifier
      therapies targeting Th2-type cytokines, however, need to be weighed against the
      toxicities associated with inhibition of key biological pathways, as well as the
      expense of future medications. Therefore, future clinical trials need to clearly
      establish the efficacy and safety of biological modifiers of Th2 immune pathways
      before these approaches can enter routine clinical practice for the treatment of
      severe asthma.

PMID- 20157139
TI  - Meta-analysis: effect of interactive communication between collaborating primary
      care physicians and specialists.
AB  - BACKGROUND: Whether collaborative care models that enable interactive
      communication (timely, 2-way exchange of pertinent clinical information directly
      between primary care and specialist physicians) improve patient outcomes is
      uncertain. PURPOSE: To assess the effects of interactive communication between
      collaborating primary care physicians and key specialists on outcomes for
      patients receiving ambulatory care. DATA SOURCES: PubMed, PsycInfo, EMBASE,
      CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews
      of Effects, and Web of Science through June 2008 and secondary references, with
      no language restriction. STUDY SELECTION: Studies that evaluated the effects of
      interactive communication between collaborating primary care physicians and
      specialists on outcomes for patients with diabetes, psychiatric conditions, or
      cancer. DATA EXTRACTION: Contextual, intervention, and outcome data from 23
      studies were extracted by one reviewer and checked by another. Study quality was
      assessed with a 13-item checklist. Disagreement was resolved by consensus. Main
      outcomes for analysis were selected by reviewers who were blinded to study
      results. DATA SYNTHESIS: Meta-analysis indicated consistent effects across 11
      randomized mental health studies (pooled effect size, -0.41 [95% CI, -0.73 to 
      0.10]), 7 nonrandomized mental health studies (pooled effect size, -0.47 [CI, 
      0.84 to -0.09]), and 5 nonrandomized diabetes studies (pooled effect size, -0.64
      [CI, -0.93 to -0.34]). These findings remained robust to sensitivity analyses.
      Meta-regression indicated studies that included interventions to enhance the
      quality of information exchange had larger effects on patient outcomes than those
      that did not (-0.84 vs. -0.27; P = 0.002). LIMITATIONS: Because collaborative
      interventions were inherently multifaceted, the efficacy of interactive
      communication by itself cannot be established. Inclusion of study designs with
      lower internal validity increased risk for bias. No studies involved oncologists.
      CONCLUSION: Consistent and clinically important effects suggest a potential role
      of interactive communication for improving the effectiveness of primary care
      specialist collaboration. PRIMARY FUNDING SOURCE: RAND Health's Comprehensive
      Assessment of Reform Options Initiative, the Veterans Affairs Center for the
      Study of Provider Behavior, The Commonwealth Fund, and the Health Foundation.

PMID- 20157140
TI  - Tobacco smoke by any other name is still as deadly.

PMID- 20157141
TI  - Seven words.

PMID- 20157143
TI  - Prediction rules must be developed according to methodological guidelines.

PMID- 20157144
TI  - The net clinical benefit of warfarin anticoagulation in atrial fibrillation.

PMID- 20157146
TI  - The net clinical benefit of warfarin anticoagulation in atrial fibrillation.

PMID- 20157147
TI  - Comparing costs and quality of care at retail clinics with those of other medical
      settings.

PMID- 20157148
TI  - Comparing costs and quality of care at retail clinics with those of other medical
      settings.

PMID- 20157149
TI  - Comparing costs and quality of care at retail clinics with those of other medical
      settings.

PMID- 20157150
TI  - Metformin stinks, literally.

PMID- 20157153
TI  - Pearls & Oy-sters: fibrocartilaginous embolism myelopathy.

PMID- 20157154
TI  - Teaching NeuroImages: idiopathic intracranial hypertension: MRI features.

PMID- 20157156
TI  - Pure autonomic failure: a restricted Lewy body synucleinopathy or early Parkinson
      disease?

PMID- 20157157
TI  - Early imaging predicts later cognitive impairment in primary progressive multiple
      sclerosis.
AB  - BACKGROUND: Cognitive impairment in primary progressive multiple sclerosis (PPMS)
      is common and correlates modestly with contemporary lesion burden and brain
      volume. Using a cohort/case control methodology, we explore the ability of MRI
      abnormalities, including those in the normal-appearing brain tissue, to predict
      future cognitive dysfunction in PPMS. METHODS: Thirty-one patients recruited into
      a longitudinal study within 5 years of onset of PPMS were assessed
      neuropsychologically on average 5.5 years later along with 31 matched healthy
      controls. MRI data obtained at entry into the study (lesion metrics, brain
      volumes, magnetization transfer ratio histogram metrics, and magnetic resonance
      spectroscopy metabolite concentrations) were used to predict cognitive impairment
      at follow-up. RESULTS: Twenty-nine percent of patients were categorized as
      cognitively impaired. T2 lesion volume was the best MRI predictor of overall
      cognitive function and performance on tests of verbal memory and attention/speed
      of information processing. Low gray matter magnetization transfer ratio was the
      best predictor of poor performance on a further test of attention/speed of
      information processing and an executive function test. Low gray and white matter
      volumes were independent predictors of poor performance on a second test of
      executive function. CONCLUSIONS: MRI abnormalities observed in early primary
      progressive multiple sclerosis can predict cognitive impairment 5 years later.
      While focal damage disrupting white matter tracts appears to be the most
      important predictor of subsequent cognitive dysfunction, gray matter pathology
      also plays a role.

PMID- 20157158
TI  - CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with
      NCL.
AB  - OBJECTIVES: To explore a potential expansion of the phenotypic and genotypic
      characteristics of Finnish variant late-infantile neuronal ceroid lipofuscinosis
      (NCL), we screened a collection of 47 patients with clinically diagnosed NCL in
      whom no molecular diagnosis had been made. METHODS: We used PCR amplification of
      genomic DNA, followed by fluorescent-labeled dideoxy-nucleotide chain termination
      sequencing and multiplex ligation-dependent probe amplification, to screen our
      cohort of patients for mutations in CLN5. We collected ethnic background,
      clinical, and pathologic information, as available, to clarify the breadth of
      CLN5 disease expression and to explore possible genotype-phenotype correlations.
      RESULTS: We identified 10 patients with pathogenic CLN5 mutations, including 11
      mutations not previously described: 4 missense, 5 out-of-frame insertion/deletion
      mutations, and 2 large intragenic deletions. We also documented 3 previously
      reported CLN5 mutations. The age at disease onset in this cohort is predominantly
      juvenile rather than late infantile. Importantly, we have identified 2 adult
      onset patients who share a common pathogenic allele. The majority of patients
      presented with motor and visual impairments and not seizures. In those patients
      with available longitudinal data, most had progressed to global
      neurodevelopmental and visual failure with seizures within 1 to 4 years.
      CONCLUSIONS: Our study suggests that CLN5 mutations 1) are more common in
      patients with neuronal ceroid lipofuscinosis (NCL) than previously reported, 2)
      are found in non-Finnish NCL patients of broad ethnic diversity, and 3) can be
      identified in NCL patients with disease onset in adult and juvenile epochs. CLN5
      genetic testing is warranted in a wider population with clinical and pathologic
      features suggestive of an NCL disorder.

PMID- 20157159
TI  - Accuracy of clinical signs, SEP, and EEG in predicting outcome of hypoxic coma: a
      meta-analysis.
AB  - OBJECTIVE: Accurate prediction of neurologic outcome after hypoxic coma is
      important. Previous systematic reviews have not used summary statistics to
      summarize and formally compare the accuracy of different prognostic tests. We
      therefore used summary receiver operating characteristic curve (SROC) and cluster
      regression methods to compare motor and pupillary responses with sensory evoked
      potential (SEP) and EEG in predicting outcome after hypoxic coma. METHODS: We
      searched PubMed, MEDLINE, and Embase (1966-2007) for reports in English, German,
      and French and identified 25 suitable studies. An SROC was constructed for each
      marker (SEP, EEG, M1 and M < or = 3), and the area under the curve (AUC), a
      measure of diagnostic accuracy, was determined. For comparison, we calculated the
      differences between the AUC for each test and M1 reference standard. RESULTS: The
      AUC for absent SEP was larger than those for M1, M < or = 3, absent pupillary
      response, and EEG when the examinations were performed within the first 24 hours.
      The difference between the AUC for SEP (AUC 0.891) and that for M1 (AUC 0.786)
      was small (0.105, 95% confidence interval 0.023-0.187), only reaching
      significance on day 1 after coma onset. The use of M < or = 3 improved the
      diagnostic accuracy of motor signs. CONCLUSIONS: This study demonstrated that
      sensory evoked potential (SEP) is marginally better than M1 at predicting outcome
      after hypoxic coma. However, the superiority of SEP diminishes after day 1 and
      when M < or = 3 is used. The findings therefore caution against the tendency to
      generalize that SEP is a better marker than clinical signs.

PMID- 20157160
TI  - Axonal variant of Guillain-Barre syndrome associated with Campylobacter infection
      in Bangladesh.
AB  - BACKGROUND: Campylobacter jejuni enteritis is the predominant bacterial infection
      preceding Guillain-Barre syndrome (GBS), an acute postinfectious immune-mediated
      polyradiculoneuropathy. The purpose of this study was to define the clinical
      phenotype of GBS and the relation with preceding C jejuni infections in
      Bangladesh. METHODS: We performed a prospective matched case-control hospital
      surveillance including 100 patients fulfilling the National Institute of
      Neurological Disorders and Stroke criteria for GBS from 2006 to 2007 in the Dhaka
      area of Bangladesh. Detailed clinical, electrophysiologic, serologic, and
      microbiologic data were obtained with a follow-up of 6 months. RESULTS: GBS
      affected predominantly young adult males living in rural areas. Sixty-nine
      percent of the patients had clinical evidence of a preceding infection. The most
      frequent symptom was diarrhea (36%). The majority of patients had a pure motor
      variant of GBS (92%) with relatively infrequent cranial nerve involvement (30%).
      Twenty-five percent of patients required respiratory support. Electrophysiologic
      studies showed that 67% of patients had an axonal variant of GBS. Eleven patients
      (14%) died, and 23 (29%) remained severely disabled during the follow-up.
      Positive C jejuni serology was found in an unprecedented high frequency of 57% as
      compared with 8% in family controls and 3% in control patients with other
      neurologic diseases (p < 0.001). C jejuni infection was significantly associated
      with serum antibodies to the gangliosides GM1 and GD1a, axonal neuropathy, and
      greater disability. CONCLUSIONS: We report an unusually high frequency of the
      axonal variant of Guillain-Barre syndrome in Bangladesh, associated with
      preceding Campylobacter jejuni infection, severe residual disability, and high
      mortality.

PMID- 20157161
TI  - Risk of recurrent stroke, myocardial infarction, or death in hospitalized stroke
      patients.
AB  - OBJECTIVE: This study examines the risk of recurrent stroke, myocardial
      infarction (MI), vascular death, or all-cause death after hospitalized stroke in
      South Carolina. METHODS: Patients with a primary diagnosis of stroke discharged
      from the year 2002 were identified from the state hospital discharge database.
      Kaplan-Meier estimates of recurrent stroke, MI, vascular death, all-cause death,
      and composite events were calculated at 1 month, 6 months, 1 year, 2 years, 3
      years, and 4 years. Prognostic factors were assessed with multivariate Cox
      proportional hazard models. RESULTS: The search strategy identified 10,399
      patients in 2002. The Kaplan-Meier estimate of cumulative risk at 1 month, 6
      months, 1 year, 2 years, 3 years, and 4 years for recurrent stroke is 1.8%, 5.0%,
      8.0%, 12.1%, 15.2%, and 18.1%; MI, 0.3%, 1.0%, 2.1%, 3.7%, 5.0%, and 6.2%; all
      cause death, 14.6%, 20.6%, 24.5%, 30.9%, 36.2%, and 41.3%; vascular death, 11.4%,
      14.8%, 17.1%, 20.7%, 23.8%, and 26.7%; and composite events of recurrent stroke,
      MI, or vascular death 13.6%, 19.5%, 24.7%, 31.6%, 36.8%, and 41.3%. The hazard
      ratio for composite events (recurrent stroke, MI, or death) increases with age
      (1.38, 1.35-1.41), is 1.12 (1.05-1.19) for African Americans compared to
      Caucasians, is 1.67 (1.57-1.77) for patients with a higher comorbidity index (>
      or = 2 vs <2), and is 1.34 (1.28-1.39) for patients with subarachnoid hemorrhage
      or intracerebral hemorrhage compared with ischemic stroke. CONCLUSIONS: These
      findings suggest there is room for further improvement in secondary stroke
      prevention in South Carolina.

PMID- 20157162
TI  - Coexisting typical migraine in familial hemiplegic migraine.
AB  - OBJECTIVE: In contrast to patients with migraine with aura (MA) and migraine
      without aura (MO), most patients with familial hemiplegic migraine (FHM) do not
      report migraine-like attacks after pharmacologic provocation with glyceryl
      trinitrate (GTN), a donor of nitric oxide. In the present study, we examined
      patients with FHM without known gene mutations and hypothesized that 1) GTN would
      cause more migraine-like attacks in patients with FHM compared to controls, and
      2) GTN would cause more migraine attacks in patients with FHM with coexisting MA
      or MO compared to the pure FHM phenotype. METHODS: The study design was a
      balanced provocation study. Twenty-three patients with FHM and 11 healthy
      controls received a continuous IV infusion of 0.5 mug/kg/min GTN over 20 minutes.
      RESULTS: We found no difference in the incidence of migraine-like attacks
      comparing all patients with FHM (30%) to controls (9%) (p = 0.15). Patients with
      FHM with coexisting MA or MO reported more migraine attacks after GTN (55%) than
      patients with the pure FHM phenotype (8.3%) (p = 0.02). Compared to healthy
      controls, more patients with FHM with coexisting MA or MO reported migraine-like
      attacks than controls (p = 0.03), whereas the FHM group with the pure FHM
      phenotype did not (p > 0.05). CONCLUSIONS: Compared to patients with migraine
      with aura (MA) and migraine without aura (MO), patients with familial hemiplegic
      migraine (FHM) without known gene mutations display a reduced sensitivity to
      nitric oxide. A subset of patients with FHM with coexisting nonhemiplegic
      migraine is more sensitive than controls. These data extend our previous findings
      that pathophysiologic pathways in FHM may differ from those of MO and MA.

PMID- 20157163
TI  - Adenosine triphosphate: a multifaceted chemical signal in the nervous system.

PMID- 20157164
TI  - alpha-synuclein accumulation in skin nerve fibers revealed by skin biopsy in pure
      autonomic failure.

PMID- 20157165
TI  - Lesional reflex epilepsy associated with the thought of food.

PMID- 20157166
TI  - Magnetic resonance finding in a seizure: truly hair-raising!

PMID- 20157167
TI  - Cancer risk among patients with multiple sclerosis and their parents.

PMID- 20157168
TI  - Migraine frequency and risk of cardiovascular disease in women.

PMID- 20157169
TI  - Dialysis treatment and regulatory T cells.

PMID- 20157170
TI  - Positron emission tomography as a tool for the 'tailored' management of
      retroperitoneal fibrosis: a nephro-urological experience.
AB  - BACKGROUND: Retroperitoneal fibrosis (RF) is a complex clinical entity
      characterized by a fibro-inflammatory reaction around the abdominal aorta and
      iliac arteries extended into the retroperitoneum. No biochemical marker
      correlates with the disease severity and progression, and imaging data fail to
      discriminate between fibrotic and florid lesions. Positron emission tomography
      (PET) was recently suggested as a promising tool to detect the disease. METHODS:
      We report on seven consecutive cases of RF managed by tailoring therapeutic
      interventions to the metabolic activity detected by PET. In 2006-09, seven
      patients with RF (five new diagnoses) were referred to the same nephro-urological
      facility. There were six males and one female aged 41-79. RF was associated with
      autoimmune diseases in three patients, with an aortic aneurysm in another three,
      and was 'idiopathic' in one. The diagnoses were made by imaging techniques
      [computed tomography (CT) or nuclear magnetic resonance (NMR)]; PET scan was
      performed in all patients in the same setting at referral and during follow-up.
      RESULTS: Patients were followed up with tailored interventions (medical therapy:
      tamoxifen, steroids, and immunosuppressors according to disease activity, side
      effects and tolerance). Six patients needed ureteral stenting for obstruction.
      PET imaging was used as a guide for the tapering of immunosuppressors and for
      stent removal. In this way, stents were safely removed when a negativization of
      disease activity was revealed by PET. Only one relapse was recorded over 163
      months of follow-up (median 24 months) detected in time by PET. CONCLUSION: PET
      is a promising tool for surveillance of disease activity and for planning the
      removal of ureteral stents in RF.

PMID- 20157171
TI  - Corticosteroids plus ACE inhibitors for IgA nephropathy.

PMID- 20157174
TI  - Whistlestop tour.

PMID- 20157175
TI  - Prevention with HIV-positive men who have sex with men: regaining lost ground.

PMID- 20157172
TI  - Effects of an oral adsorbent on oxidative stress and fibronectin expression in
      experimental diabetic nephropathy.
AB  - BACKGROUND: Previous studies have demonstrated that AST-120 (Kremezin((R))), a
      well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM
      chronic kidney disease along with a decrease in oxidative stress. This study was
      undertaken to investigate whether AST-120 could reduce oxidative stress and
      ameliorate the development of nephropathy in experimental DM rats with normal
      renal function. METHODS: Rats were injected with diluent (C, n = 16) or 65 mg/kg
      streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group
      were treated with chow containing 5% AST-120. After 3 months, plasma advanced
      oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h
      urinary albumin excretion, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG)
      excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase
      (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein
      expressions were determined by real-time PCR and western blot, respectively. In
      addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to
      detect glomerular reactive oxygen species (ROS) production. RESULTS: Compared to
      the C group, 24-h urinary albumin excretion was significantly higher in the DM
      group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM
      rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were
      significantly increased in DM rats compared to C rats, and these increases in DM
      glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The
      increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM
      rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also
      significantly attenuated by AST-120 treatment (P < 0.05). CONCLUSION: In
      conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be
      associated with the amelioration of enhanced oxidative stress and FN expression
      under diabetic conditions.

PMID- 20157177
TI  - Trends in the epidemiology of bacterial sexually transmitted infections in
      eastern Europe, 1995-2005.
AB  - BACKGROUND: Sexually transmitted infections (STI) are a significant public health
      problem both worldwide and in Europe. This article reviews trends in the
      epidemiology of the major bacterial STI in eastern European countries, their key
      determinants, as well as challenges and opportunities for enhancing STI control
      in the region. SEARCH STRATEGY: Publications were sought through computerised
      searches in PubMed from 1995 to 2008 using using free text and relevant medical
      subject headings with no language restrictions. Conference abstracts and other
      unpublished manuscripts were excluded. RESULTS: The reported rates of STI in many
      eastern European countries have either decreased (syphilis and gonorrhoea in the
      eastern/Russian regions, gonorrhoea throughout eastern Europe) or been relatively
      stable (syphilis in the southeastern region, chlamydia throughout eastern
      Europe), in the past decade, but are still significantly higher than in western
      Europe. There is a significant east-west geopolitical gradient in reported STI
      rates throughout eastern Europe (STI rates: Russia/eastern region>>southeastern
      region>central region). Challenges for STI control include: the need to
      strengthen public health components of control; improvements in surveillance and
      improvement, as well as quality assurance, in diagnostic strategies. Gains in STI
      control may be achieved through greater collaboration and harmonisation of
      practicss at the European level.

PMID- 20157178
TI  - Does it fit okay? Problems with condom use as a function of self-reported poor
      fit.
AB  - OBJECTIVE: To identify associations between men's self-reports of ill-fitting
      condoms and selected condom use problems, using an event-specific analysis.
      METHODS: A convenience sample of men was recruited via advertisements in
      newspapers (two urban and one small town) and a blog on the website of a condom
      sales company. Men completed a questionnaire posted on the website of The Kinsey
      Institute for Research in Sex, Gender, and Reproduction. Inclusion criteria were:
      at least 18 years old, used condoms for penile-vaginal intercourse in the past 3
      months and the ability to read English. RESULTS: In controlled, event-specific,
      analyses of 436 men, those reporting ill-fitting condoms (44.7%) were
      significantly more likely to report breakage (adjusted odds ratio (AOR 2.6),
      slippage (AOR 2.7), difficulty reaching orgasm, both for their female partners
      (AOR 1.9) and for themselves (AOR 2.3). In addition, they were more likely to
      report irritation of the penis (AOR 5.0) and reduced sexual pleasure, both for
      their female partner (AOR 1.6) and for themselves (AOR 2.4). Furthermore, they
      were more likely to report that condoms interfered with erection (AOR 2.0),
      caused erection loss (AOR 2.3), or became dry during sex (AOR 1.9). Finally, they
      were more likely to report removing condoms before penile-vaginal sex ended (AOR
      2.0). CONCLUSIONS: Men and their female sex partners may benefit from public
      health efforts designed to promote the improved fit of condoms.

PMID- 20157179
TI  - Addressing the high prevalence of gonorrhoea and chlamydia among female sex
      workers in Indonesia: results of an enhanced, comprehensive intervention.
AB  - OBJECTIVES: The authors developed a comprehensive STI-control programme to
      decrease gonorrhoea and chlamydia prevalence, and increase consistent condom use
      among brothel-based sex workers in Indonesia. METHODS: The STI-control programme
      for brothel-based sex workers in Bintan Island (Riau Islands) and Salatiga
      (Central Java) included (1) provision of adequate drugs for gonorrhoea and
      chlamydia as periodic presumptive treatment (PPT) followed by syndromic
      treatment; (2) condom-use promotion by involving the local community and ensuring
      sufficient condom supply. Endocervical samples were collected and tested for
      gonorrhoea and chlamydia by PCR. Cross-sectional assessments of gonorrhoea and
      chlamydia prevalence, and consistent condom use with clients in the last week
      were made at several time points for sex workers attending the STI clinic.
      RESULTS: 580 sex workers participated in the programme. A steady decrease in
      prevalence was observed for gonorrhoea (36.1-7.6%) and chlamydia (33.7-10.2%)
      (both p<0.01) among sex workers in Bintan from March 2008 until June 2009. Sex
      workers in Salatiga showed a sharp initial decrease in prevalence, followed by an
      increase after provision of the old drug regimen. Gonorrhoea and/or chlamydia
      prevalence among those who had received at least one PPT round was lower compared
      with that in newcomers (p<0.01). The proportion of sex workers reporting
      consistent condom use doubled to 40% in June 2009 compared with November 2007
      (p<0.01). CONCLUSION: The STI-control programme was effective in reducing
      infection prevalence and increasing condom use among sex workers. This
      intervention has been scaled up and may decrease national STI levels and reduce
      HIV transmission.

PMID- 20157188
TI  - Do stressful working conditions cause psychiatric disorders?

PMID- 20157180
TI  - Results of a phase I/II study of ocrelizumab, a fully humanized anti-CD20 mAb, in
      patients with relapsed/refractory follicular lymphoma.
AB  - BACKGROUND: Ocrelizumab is a humanized anti-CD20 antibody with increased antibody
      dependent cellular cytotoxicity compared with rituximab. This phase I/II study
      evaluated its safety and efficacy in patients with relapsed/refractory follicular
      lymphoma (FL) after prior rituximab therapy. DESIGN AND METHODS: Forty-seven
      patients were treated in three dose cohorts and received eight infusions every 3
      weeks: cohort A, 200 mg/m(2) (n = 15); cohort B, 375 mg/m(2) (n = 16); cohort C,
      first dose 375 mg/m(2), seven subsequent doses of 750 mg/m(2) (n = 16). Patients
      were assessed for safety, efficacy, pharmacodynamics and pharmacokinetics.
      RESULTS: The median patient age was 58 years, the majority had Ann Arbor stage
      III/IV disease and had received a median of 2 (range 1-6) prior regimens.
      Ocrelizumab was well tolerated with grade 3/4 toxicity occurring in 9% of
      patients. The most common toxicity was infusion-related reactions (74% patients),
      all grade 1/2 except one grade 3 event. The objective response rate was 38% and
      was similar in patients with low-affinity and high-affinity variants of the
      Fcgamma receptor IIIa (FcgammaRIIIa). With follow-up of approximately 28 months,
      the median progression-free survival was 11.4 months. CONCLUSION: Ocrelizumab
      demonstrated activity in patients with relapsed/refractory FL following prior
      rituximab treatment, with safety similar to rituximab although adverse events
      appeared milder.

PMID- 20157189
TI  - John Brack Collins Street 5 p.m., 1955.

PMID- 20157190
TI  - Fatigue Impact Scale.

PMID- 20157191
TI  - Plasma insulin-like growth factor-binding protein-2 levels as diagnostic and
      prognostic biomarker of colorectal cancer.
AB  - CONTEXT: Overexpression of IGF-II and IGF-binding protein (IGFBP)-2 has been
      reported in several cancers. OBJECTIVE: We aimed to assess the roles of plasma
      IGF-II and IGFBP-2 levels as diagnostic and prognostic biomarkers and the impact
      of loss of imprinting (LOI) of IGF-II on the survival of colorectal cancer (CRC).
      DESIGN: We conducted a case control and prospective cohort study for diagnostic
      and prognostic values, respectively. PATIENTS AND SETTING: Plasma levels of IGF
      II and IGFBP-2 were measured in 162 patients with CRC before surgery, in paired
      15 patients after curative surgery, in 24 patients with advanced colon polyps,
      and in 114 healthy controls between 2003 and 2006 in National Taiwan University
      Hospital. RESULTS: The area under the curve values of using IGFBP-2 as a
      diagnostic marker for advanced colon polyp and CRC were 0.654 [95% confidence
      interval (CI) = 0.547-0.76; P = 0.017] and 0.815 (95% CI = 0.766-0.864; P <
      0.001), respectively. The sensitivity and specificity for diagnosing CRC were
      80.2 and 64%, respectively, if the cutoff value of IGFBP-2 was 377 ng/ml. In the
      multivariate Cox proportional hazards regression model, higher IGFBP-2 levels
      were associated with increased risk of mortality [hazard ratio (HR) = 2.46; P =
      0.017], whereas higher IGF-II levels were associated with reduced risk of
      mortality (HR = 0.42; P = 0.044). LOI of IGF-II was associated with increased
      risk of mortality (HR = 7.91; P = 0.014) in patients with stage IV disease.
      CONCLUSIONS: IGFBP-2 is a potential diagnostic and prognostic biomarker of CRC.
      LOI of IGF-II is significantly associated with poor prognosis in patients with
      stage IV disease.

PMID- 20157192
TI  - Transcription factor mutations and congenital hypothyroidism: systematic genetic
      screening of a population-based cohort of Japanese patients.
AB  - CONTEXT: Gene mutations of transcription factors that are predominantly expressed
      in the thyroid gland cause congenital hypothyroidism (CH). The prevalence of CH
      due to transcription factor mutations remains undetermined. OBJECTIVE: This study
      was designed to define the prevalence of CH due to mutations of PAX8, NKX2-1
      [encoding thyroid transcription factor (TTF)-1], FOXE1 (encoding TTF-2), and NKX2
      5 among patients with permanent primary CH and in the general population in
      Japan. SUBJECTS AND METHODS: We enrolled 102 CH patients that represent 353,000
      newborns born in Kanagawa prefecture from October 1979 to June 2006. We sequenced
      PAX8, NKX2-1, FOXE1, and NKX2-5 using PCR-based methods. Additionally,
      deletion/duplication of PAX8, NKX2-1, and FOXE1 was screened by multiplex
      ligation-dependent probe amplification. Molecular functions of putative mutations
      were verified in vitro. RESULTS: We identified a novel small duplication of PAX8
      (p.K80_A84dup) in two half-sibling patients with thyroid hypoplasia. We also
      found a novel NKX2-1 variation (p.H60W) in a sporadic nonsyndromic CH patient. In
      vitro experiments showed that K80_A84dup PAX8 had impaired transactivation of the
      thyroglobulin promoter. H60W TTF-1 exhibited a comparable transactivating
      capacity with wild-type TTF-1, suggesting a benign variation. We estimate the
      prevalence of PAX8 mutations to be 2.0% (two in 102) among Japanese CH patients
      and one in 176,000 (two in 353,000) in the general Japanese population.
      CONCLUSIONS: Using a population-based sample, we confirmed that a minor subset of
      CH patients has transcription factor mutations, but they are rare. In our cohort,
      PAX8 mutations were the leading cause of such a rare condition.

PMID- 20157193
TI  - Cushing syndrome in the McCune-Albright syndrome.
AB  - CONTEXT: Cushing syndrome (CS) is a rare but potentially fatal feature of McCune
      Albright syndrome (MAS). Optimal management, prognostic features, and long-term
      follow-up of this disorder have not been described. SETTING: The study was
      conducted at an academic tertiary care center. PATIENTS: A total of 112 patients
      participating in a natural history study at the National Institutes of Health
      (NIH) were evaluated, and 21 published cases were reviewed. INTERVENTIONS:
      Subjects received observation, medical management, or bilateral adrenalectomy.
      MAIN OUTCOME MEASURES: We measured prevalence, prognostic factors, and natural
      history. RESULTS: The prevalence of CS among NIH patients was 7.1%. The median
      age at diagnosis was 3 months. Clinical features included "Cushingoid facies"
      (66.7%), failure to thrive (60.0%), low birth weight (50.0%), liver disease
      (36.7%), and heart disease (26.7%). Six patients (20.0%) died, four after
      adrenalectomy. Death was more likely in patients with comorbid heart disease
      (odds ratio, 13.3; P < 0.05). Of 23 survivors, 13 underwent adrenalectomy, and 10
      exhibited spontaneous resolution. Two patients with spontaneous resolution who
      were tested later in life (3 and 15 yr after resolution) continued to have low
      level, autonomous adrenal function with biochemical adrenal insufficiency.
      Compared to MAS patients without CS, patients with CS were more likely to have a
      cognitive/developmental disorder (44.4 vs. 4.8%; P < 0.001; odds ratio, 8.8).
      CONCLUSIONS: Comorbid heart and liver disease were poor prognostic markers and
      may indicate the need for prompt adrenalectomy. The high incidence of cognitive
      disorders indicates a need for close developmental follow-up and parental
      counseling. Patients with spontaneous resolution of CS may develop adrenal
      insufficiency, and they require long-term monitoring.

PMID- 20157194
TI  - Effects of sex, race, and puberty on cortical bone and the functional muscle bone
      unit in children, adolescents, and young adults.
AB  - CONTEXT: Sex and race differences in bone development are associated with
      differences in growth, maturation, and body composition. OBJECTIVE: The aim of
      the study was to determine the independent effects of sex, race, and puberty on
      cortical bone development and muscle-bone relations in children and young adults.
      DESIGN AND PARTICIPANTS: We conducted a cross-sectional study of 665 healthy
      participants (310 male, 306 black) ages 5-35 yr. OUTCOMES: Tibia peripheral
      quantitative computed tomography measures were made of cortical bone mineral
      content (BMC) and bone mineral density (BMD), periosteal (Peri) and endosteal
      circumferences, section modulus (Zp), and muscle area. Regression models were
      adjusted for tibia length, age, race, sex, and Tanner stage. RESULTS: All
      cortical measures were greater in blacks than whites (all P < or = 0.001) in
      Tanner stages 1-4; however, differences in BMC, Peri, and Zp were negligible in
      Tanner stage 5 (all interactions, P < 0.01). Cortical BMC, Peri, and Zp were
      lower in females than males in all Tanner stages (all P < 0.001), and the sex
      differences in Peri and Zp were greater in Tanner stage 5 (interaction, P <
      0.02). Cortical BMD was greater (P < 0.0001) and endosteal circumference was
      lower (P < 0.01) in Tanner 3-5 females, compared with males. Adjustment for
      muscle area attenuated but did not eliminate sex and race differences in cortical
      dimensions. Associations between muscle and bone outcomes did not differ
      according to sex or race. CONCLUSION: Sex and race were associated with
      maturation-specific differences in cortical BMD and dimensions that were not
      fully explained by differences in bone length or muscle. No race or sex
      differences in the functional muscle bone unit were identified.

PMID- 20157195
TI  - Treatment of X-linked hypophosphatemia with calcitriol and phosphate increases
      circulating fibroblast growth factor 23 concentrations.
AB  - CONTEXT: X-Linked hypophosphatemia (XLH) is characterized by renal phosphate
      wasting, with inappropriately low or normal serum 1,25-dihydroxyvitamin D
      concentrations causing rickets and osteomalacia. Mutations in PHEX result in
      increased fibroblast growth factor 23 (FGF23) expression, elevating circulating
      FGF23 concentrations. Treating XLH with phosphate and calcitriol may further
      increase FGF23 concentrations, based on in vitro and in vivo models. OBJECTIVE:
      The aim of the study was to investigate whether current standard XLH therapies
      increase circulating FGF23 concentrations. DESIGN AND SETTING: We conducted a
      prospective observational study of XLH subjects during routine clinical
      management at two tertiary referral centers. PATIENTS: The study included 10 XLH
      patients (seven children, three adults; age, 2-30 yr) initiating therapy and five
      XLH patients (age, 18-41 yr) electing not to undergo therapy. INTERVENTION(S):
      Oral calcitriol and phosphate were administered. MAIN OUTCOME MEASURES: We
      measured circulating intact FGF23 concentrations. RESULTS: Baseline circulating
      FGF23 concentrations were elevated in 14 of 15 subjects, increasing after
      treatment in most subjects. Follow-up was 14.4 +/- 11.7 months (treatment cohort)
      and 25 +/- 32 months (nontreatment cohort). FGF23 concentrations increased 132.7
      +/- 202.4% from pretreatment to peak during therapy but did not change
      significantly over time in the nontreatment cohort. FGF23 concentrations were
      related to phosphate doses (P = 0.04) and nonsignificantly to calcitriol doses (P
      = 0.06). CONCLUSIONS: Treating XLH with phosphate and calcitriol was associated
      with concurrent increases in circulating FGF23 concentrations, which may diminish
      therapeutic effect or contribute to complications of therapy. Because it is
      unknown whether the degree of FGF23 elevation correlates with disease severity in
      XLH, further study is needed to determine whether adjusting therapy to minimize
      effects on FGF23 concentration is warranted.

PMID- 20157198
TI  - Incidence and risk factors of nosocomial infections after cardiac surgery in
      Georgian population with congenital heart diseases.
AB  - Nosocomial infections still remain a serious problem in patients undergoing open
      heart surgery. The aim of the study was to determine the incidence, etiology and
      main risk factors of nosocomial infections (NI) following cardiac surgery in
      congenital heart diseases population. Retrospective case study was conducted. 387
      patients with congenital heart disease (CHD), who underwent cardiac surgery from
      January 2007 to December 2008 were studied. The age of the most patients varied
      between 1 day to 15 years, 73 patients (18,8%) were older than 15 years. All 387
      patients underwent cardiac surgery. The rate of NI was 16%. The most common
      infections were bloodstream infections (BSI) (7,75%) and respiratory tract
      infections (7%) respectively. The rate of NI was higher in patients under 1 year
      of age, after urgent surgery and urgent reoperation, long cardiopulmonary bypass
      (CPB) and aortic cross-clamp time, also in patients with prolonged mechanical
      ventilation, massive haemotransfusion, with open heart bone after surgery,
      reintubation, hospitalization in another hospital during last three month. It was
      concluded that the most common nosocomial infection after cardiac surgery
      congenital heart diseases in Georgian population was blood stream infection. The
      main risk factors of NI in the same setting were age under 1 year, urgent
      surgery, urgent reoperation, long CPB and aortic cross-clamp time, long duration
      of mechanical ventilation, massive haemotransfusion, open heart bone after
      surgery, reintubation, hospitalization in another hospital during last three
      month.

PMID- 20157196
TI  - The influence of glomerular filtration rate and age on fibroblast growth factor
      23 serum levels in pediatric chronic kidney disease.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic factor and a
      suppressor of 1alpha-hydroxylase activity in the kidney. Although its importance
      in chronic kidney disease (CKD) has been demonstrated in adults, there is little
      information in pediatric patients. OBJECTIVES: The aims of this study were: 1) to
      determine reference values for FGF23 serum levels according to glomerular
      filtration rate (GFR) (measured by the reference standard, inulin clearance),
      gender, and age; and 2) to evaluate the effects of different etiologies and
      treatments on FGF23 serum levels in a prospective single-center cohort of 227 CKD
      children (119 boys). RESULTS: Age, body weight, height, and GFR (mean +/- sd)
      values were: 11.3 +/- 4.1 yr, 37 +/- 16 kg, 140 +/- 20 cm, and 98 +/- 34 ml/min
      per 1.73 m(2), respectively. Calcium, phosphate, PTH, 25 hydroxyvitamin D, 1,25
      dihydroxyvitamin D, C-terminal FGF23, and intact FGF23 (mean +/- sd) levels were:
      2.43 +/- 0.11 mmol/liter, 1.41 +/- 0.22 mmol/liter, 41 +/- 23 pg/ml, 24 +/- 10
      ng/ml, 152 +/- 72 pmol/liter, 76 +/- 134 relative units/ml, and 44 +/- 37 pg/ml,
      respectively. There was a wide range of FGF23 serum levels, but FGF23 levels
      increased when GFR decreased. FGF23 serum levels were not modified by gender, but
      they increased with age. In univariate analysis, corticosteroid therapy seemed to
      be associated with increased FGF23 serum levels. A multivariate linear regression
      analysis found a significant impact of GFR, body mass index, and solid organ
      transplantation on FGF23 serum levels. CONCLUSION: Age, GFR, body mass index, and
      solid organ transplantation seem to influence FGF23 serum levels in a pediatric
      population. The impact of corticosteroids on FGF23 metabolism should be further
      investigated; further longitudinal studies will also help to better define the
      prognostic impact of FGF23 serum levels in pediatric CKD in terms of disease
      progression, cardiovascular morbidities, and bone disabilities.

PMID- 20157197
TI  - Effects of pioglitazone on intramyocellular fat metabolism in patients with type
      2 diabetes mellitus.
AB  - CONTEXT: Lipotoxicity (increased tissue fat content) has been implicated in the
      development of muscle insulin resistance and type 2 diabetes mellitus (T2DM).
      OBJECTIVE: The aim was to study the effect of pioglitazone on intramyocellular
      fat metabolism. RESEARCH DESIGN: Twenty-four T2DM subjects (glycosylated
      hemoglobin = 8.3 +/- 0.4%) participated in three similar study protocols before
      and after 4 months of 45 mg/d pioglitazone treatment: 1) 3-h euglycemic insulin
      (80 mU/m(2) . min) clamp with measurement of intramyocellular fat with proton
      nuclear magnetic resonance; 2) vastus lateralis muscle biopsy for measurement of
      LC-FACoAs 60 min before start of the insulin clamp; and 3) muscle biopsy for
      measurement of diacylglycerol 60 min before start of the insulin clamp. RESULTS:
      In all three protocols, pioglitazone similarly reduced (all P < 0.05) the
      glycosylated hemoglobin (Delta = 0.8-1.2%), fasting plasma glucose (39-76 mg/dl),
      fasting free fatty acid (132-236 mumol/liter), and increased insulin-stimulated
      glucose disposal (by 25-56%). Intramyocellular fat (protocol I) declined from 1.5
      to 0.9% (P < 0.05) and correlated with the increase in glucose disposal rate (r =
      0.65; P < 0.05). Long chain-fatty acyl-coenzyme A decreased from 12.5 to 8.1
      nmol/g (P < 0.05) and correlated with the increase in disposal rate (r = 0.76; P
      < 0.05). Pioglitazone therapy had no effect on muscle diacylglycerol content.
      CONCLUSIONS: Pioglitazone improves insulin resistance in T2DM in association with
      mobilization of fat and toxic lipid metabolites out of muscle.

PMID- 20157200
TI  - [Importance of color Doppler in diagnostics of breast diseases].
AB  - The breast cancer occupies one of the first places among women's malignant
      neoplasms. Breast cancer case rate annually increases in the majority of the
      countries of the world. It is very important early diagnostics and active
      revealing of breast pre-tumor diseases. With the purpose of definition of value
      of color Doppler, there were inspected 127 patients with various breast
      pathologies. Breast ultrasonic research, color Doppler and power Doppler allowed
      obtaining the essential additional data for carrying out of differential
      diagnostics. According to the results, concentration of vessels in a zone of
      tumor unit with a primary locating on periphery is characteristic for malignant
      formations of breast. It is, accordingly, cause of rising vascularisation of
      tissues of breast, and also high parameters of linear speed of blood-flow - Vmax 
      0,34+/-0,05 m/s, Pi (Pulls index )- 1,42+/-0,04, Ri (Resistance index) - 0,71+/
      0,02. Parameters of linear rate of a blood-flow are lower for non malignant nodal
      formations - Vmax from 0,14+/-0,02-0,19+/-0,02 m/s, Pi - 1,42+/-0,12-1,42+/-0,06,
      Ri - 0,60+/-0,02-0,62+/-0,02. In cases of weak vascularised of nodal formations
      the method of power Doppler was used. The maximal rate in circumflex vessels of
      the pathological formations in most cases did not exceed 0,25 m/s, when size of
      formation was up to 1,5 sm and 0,7 m/s when size of formations was more than 3
      sm. At use of ultrasonic intervention combining with color Doppler and power
      Doppler sensitivity of diagnostics has made 93,8% and specificity - 88,6%.
      Proceeding from, color Doppler especially in a combination to other methods of
      research is the effective method, allowing increase of diagnostic accuracy.
      Dopplerography, allowing to visualization of blood-flow in fine vessels and even
      perfusion in a tissue of breast, undoubtedly, soon will occupy the one of the
      conducting places in diagnostics of breast diseases.

PMID- 20157199
TI  - Treatment of postoperative esophageal leak by active drainage procedure (case
      report).
AB  - Postoperative esophageal leak is still a very serious and complex problem, which
      is associated with poor results, because of considerable morbidity and mortality
      rate. We described the case of successful treatment of suture line leak of 53
      year old patient after resection of a big size epiphrenic diverticulum.
      Traditional right-sided transthoracic approach in 7th intercostal space with
      dissection, exposure and resection of diverticulum by stapler with 40F bougie
      within the esophagus was performed with reinforcement of suture line. On 6th
      postoperative day the control water-soluble contrast X-ray examination was done
      and pleural effusion and suture line disruption was found. Immediately under X
      ray control the large diameter chest tube (Ch24) was inserted and periesophageal
      mediastinum as well as pleural cavity was drained and active aspiration with
      simultaneously irrigation/lavage procedures was started. Parallel fasting,
      systemic antibiotic therapy was started and feeding balloon catheter gastrostomy
      by Stamm was created. The healing process of the leak was controlled every week
      by water-soluble contrast swallow and the chest drain tubes were twice changed
      (Ch20 and Ch14) during the treatment. The complete healing and closure of the
      leak was achieved after 2,5 month of starting the treatment by using this method.
      Our case have demonstrated, that aggressive conservative treatment approach with
      combination of: active and adequate drainage of the leak site, systemic
      antibiotic therapy, nutritional support by feeding gastrostomy with frequent
      radiologic examinations for monitoring of healing process is the effective and
      safe treatment of esophageal leaks.

PMID- 20157201
TI  - [Morphological index for prediction of cervix uteri cancer].
AB  - The aim of the research is evaluation of morphological parameters which would
      allow predicting cervix uteri cancer. The case histories of 505 patients (from 20
      to 70 years old) with I-III clinical stages of primary cervical uteri cancer
      (PUC), which got surgical and combined treatment in oncological center in Batumi
      from 1970-2005 were evaluated. The factors that influence on the prognosis of PUC
      are revealed: cancer cell emboli in vessels of tumour stroma, sharpness of the
      tumour edges, the tumor tissue types, and the depth of invasion. The imaging
      characteristics of the tumours are described. Planocellular cancer has more
      favourable prognosis in comparison with glandular cancer.

PMID- 20157202
TI  - [Influence of TORCH-infections on the spermatogenesis of men].
AB  - The purpose of the given study was to reveal causal relations between infection
      of the urino-genital tract by intracellular parasites, the so-called TORCH
      infections, and the decrease of spermatogenesis. For observation 182 men of
      reproductive age (from 22 to 38 years) with oligozoospermia and aspermia, without
      any complaints or clinical symptoms indicating existence of infections of urino
      genital tracts, were selected. Out of those, 131 revealed oligozoospermia, i.e.
      the quantity of spermatozoons was no higher than 20 mln in 1 ml of ejaculate, and
      51 revealed - aspermia. For examination of some TORCH infections, medical doctors
      in charge directed 44 oligozoospermia patients and 15 aspermia patients, who
      respectively constituted group I and group II. Examinations were carried out for
      Chlamydia trachomatis--(Ch.t), Herpes simplex virus--(HSV), Ureaplasma
      urealiticum--(U.u.), Cytomegalovirus--(CMV), and Mycoplasma hominis--(M.h.). In
      the group with oligozoospermia, cases of infections by Chlamydias (41.5%) and
      Herpes virus (51.3%) were frequent, but Ureaplasma (56,5%) was more frequent than
      any infections. Cytomegalovirus occurred in the least number of cases. Making any
      conclusions on the frequency of infections by M.h. is difficult due to the low
      number of examinations. Similar picture was observed in Group II as well.
      Following successful treatment of infections in Group I, 8 patients with Ch.t.
      and 8 patients with U.u. showed an improved spermogram after several months.
      Treatment of other infections did not yield tangible results. In Group II
      spermatogenesis remained without any changes.

PMID- 20157203
TI  - [Chromatography analysis of tobacco smoke condensate in biology tissue].
AB  - Specialized analytical instrumentation for detailed analysis of nicotine,
      benz(alpha)pyrene, pyridine and benzene in tooth enamel and pulp of inveterate
      tobacco smokers is created. A Waters PPY-24 liquid chromatograph is equipped with
      Model M660 solvent programmer and a Model U6K sample injector is used. A Model
      440 dual-wavelength detector is used to obtain absorbance ratios on dual-pen
      recorder. Our data show that concentration of tobacco smoke components in tooth
      cavity of inveterate tobacco smokers is different. The chisel tooth pulp
      contained considerably more nicotine and pyridine as compared with molars. The
      level of benzene does not change analyzed structures. The assumption of linearity
      between calculation of predicted retention times and concentration has been shown
      to be valid up to about 8,0% for all studied compounds.

PMID- 20157204
TI  - [Influence of treatment with vanadium intranasalelectrophoresis on clinical
      conditions of patients with allergic rhinitis].
AB  - High prevalence of allergic rhinitis makes more topical the problem of search of
      new, more effective means of treatment this pathology. 67 patients with allergic
      rhinitis were examined. 35 of them had persistent form of pathology and 32 of
      them--intermittent form of allergic rhinitis. It has been established, that
      treatment by vanadium intranasal electrophoresis caused attenuation, up to
      disappearance of the complaint, has a normalizing action on smelling function of
      nose, motor activity of scintillans epithelial of nasal mucosa and other
      objective indexes of clinical status. The above shown positive shifts were more
      positive pronounced in patients with intermittent form of allergic rhinitis.

PMID- 20157205
TI  - [Risk of myocardial infarction in out-patient treatment of patients with type 2
      diabetes].
AB  - The aim of this study was the identification of risk of myocardial infarction in
      out-patient treatment of type 2 diabetes. The study was carried out on 340
      patients with type 2 diabetes. The risk of ischemic disease was determined during
      10 years by PROCAM program. It was found that 178 (52.4%) patients with type 2
      diabetes had law risk of development of myocardial infarction, 89 (26.2%)
      patients - moderate and 73 patients (21.4%) - the high risk of myocardial
      infarction. The following interconnection was determined: the age of the
      patients(r=+0,46; P<0,001); the family history of diabetes (r=+0,22; P<0,01);
      smoking (r=+0,23; P<0,01); systolic arterial pressure (r=+0,18; P<0,05);
      cholesterol (r=+0,20; P<0,01); high-density lipoprotein (r=-0,24; P<0,001); low
      density lipoprotein (r=+0,21; P<0,001).

PMID- 20157206
TI  - [Correlative analysis between indices of rheological particularities of blood, IL
      1beta and lipid profile in patients with chronic cor pulmonary].
AB  - Cor pulmonary is a partial complication of majority chronic light diseases and
      despite its prolonged study many questions of this problem still remain unsolved
      and disputable, complicated diagnosis of diseases at early stages, its
      development, treatment is of little efficiency and the rate of deaths is high.
      Working-out the algorithm of the diagnosis of cor pulmonary on the grounds of
      mathematical modeling and analysis of laboratory indices. Worked-out
      dimensionless parameters of more informational indices of aggregate
      particularities of formal elements of blood, lipid spectrum, the level human
      interleukin 1beta irrespective each other with the record of permissible diapason
      permit diagnosing the early stages of disease, estimate its dynamics and make
      provisions against its further development.

PMID- 20157207
TI  - [Dimensionless coefficients counted on the grounds of instrumental indices in
      patients with chronic cor pulmonary].
AB  - Cor pulmonary remains one of the actual tasks of modern pulmonogy, cardiology.
      The aim of the investigation is working-out algorithm diagnoses of cor pulmonary
      on the grounds of mathematical modeling and analyses of the results of several
      instrumental indices. The results of the investigation indices showed that worked
      out by means of mathematical analyses the dimensionless coefficients permit find
      out the necessary instrumental indices for CP diagnose. Dimensionless
      coefficients promote control over the efficiency of treatment and also enable the
      development of new optimal scheme CP therapy.

PMID- 20157208
TI  - The parameters of physical growth in 5-6 years old children in Tbilisi.
AB  - The aim of the study was to assess nutritional status and anthropometric
      parameters in children aged 5-6 and to identify possible factors influencing the
      growth pattern of Georgian children. The cross-sectional study was performed on a
      sample of 754 children boys and girls aged 5-6 attending preschool facilities and
      their main caregivers in the study sites. The study covered children population
      from 16 kindergartens of 2 regions (Gldani-Nadzaladevi, and Vake-Saburtalo) of
      Tbilisi, with different social-economical status. The following anthropometric
      parameters were studied--body weight, height, head and mid arm circumferences and
      body mass index (BMI). Physical parameters were assessed using WHO/NIH
      standardized growth charts (percentile and Z scores). Collected data was analyzed
      using the computer program EPI INFO. High weight and height (> 95 percentile/2 Z
      score) was found more frequently than low (< 5 percentile/-2 Z score) parameters.
      Most children's weight according to their stature was in normal 5-95 percentile
      range. At the same time in girls was often met low weigh for their stature then
      in boys. The imbalance between the weight and height is more evident than between
      weight and age or height and age. The results showed that the abnormal Z scores
      more or below +/-2 scores were in less percents of children then high and low
      weight and height by the age in percentiles. The results showed a prevalence of
      children having normal indices of BMI between 5 and 85 percentiles, approximately
      13%of children have low weight (less than 5 percentile), approximately 18% have
      risk of overweight and 16% have obesity. A multivariate analysis of personal and
      nutritional variables with the standard nutritional indicators identified age,
      sex, bottle feeding, and type of solid foods as significant risk factors for
      stunted growth. Stunting increases with age and males have poorer growth pattern
      than females. The results of the study emphasize that in Tbilisi 5-6 years old
      child population more frequent is problem of overweight and obesity than
      underweight.

PMID- 20157209
TI  - Effects of excitotoxic lesions of the CA1 region of the hippocampus on
      acquisition of a place and cue water maze task.
AB  - The aim of the present study was to investigate the effects of excitotoxic
      lesions of the dorsal CA1 region of the hippocampus on acquisition of a place and
      cue water maze task. The ibotenic acid injections into CA1 produced removal of
      the pyramidal cells in CA1, while saving most of the pyramidal cells in CA3 and
      granule cells in DG intact. In conditions of visible platform training trials,
      differences in the platform reaching latency between the animals of different
      groups, were not found. When testing was performed in conditions of submerged
      platform, the latency of the platform finding was significantly increased
      (P<0.05). This fact certifies for deficit of the place learning strategy in the
      CA1-lesioned rats. Decreased place-bias in CA1-lesioned rats in hidden platform
      training trials compared to the sham-operated rats was significant, but in
      testing trials when required to choose between the spatial location they had
      learned and the visible platform in a new location majority of them swam first to
      the old spatial location. Decreased place-bias in CA1-lesioned rats compared to
      the sham-operated rats was not significant. We suggest that spatial learning
      deficits observed after dorsal hippocampal lesions cannot be accounted solely to
      the loss of dorsal hippocampal CA1 region cells.

PMID- 20157210
TI  - Object exploration and reactions to spatial and nonspatial changes in dentate
      gyrus lesioned rats.
AB  - In order to investigate the possible involvement the DG in spatial and object
      recognition memory, we have opted for a non-associative task where no explicit
      reward was present. Colchicine was used for bilateral DG lesions for its well
      known specificity for DG lesion. Colchicine-induced lesions produce severe damage
      in the granule cells of DG, while minimally affecting pyramidal cells in CA1 and
      CA3. The main results are as follows: The overall habituation to the familiar
      environment in DG lesioned rats was decreased than in sham operated rats. There
      was no significant impairment in detecting spatial novelty. Lesions of the DG did
      not affect the detection of a novel object placed in a familiar location.
      Considering both the impaired habituation and the generally intact detection of
      spatial changes, we suggest that exploratory activity in relation to the entire
      environment and to the particular objects is thought to be subserved by diverse
      nervous substrate, and testing in the given conditions allows for their
      differential estimation.

PMID- 20157211
TI  - [Iodine deficiency in the prenatal period may form learning ability deficiency in
      the postnatal period].
AB  - The present study analysis the changes in learning ability of the progeny of rats
      suffered from iodine deficiency. Reduction of serum thyroxin in the mothers'
      blood during three months before mating and whole period of gestation to an
      average level of 4,7+/-0,6 ng/ml, significantly worsened the learning ability in
      progeny, and the reduction to 1,1+/-0,4 ng/ml - completely deprived progeny's
      learning ability. Passage of the maze for these animals was purely probabilistic
      in nature without any signs of learning We can conclude that the diet with very
      low iodine content results in a low level of thyroxin in maternal serum and
      neurological deficiency in progeny manifested by learning disability during maze
      testing. Addition of the iodine to the diet prevents development of mentioned
      neurological deficiency.

PMID- 20157212
TI  - Human rights for better quality of life.
AB  - This article reviews problems of pain relief for incurable patients, in the
      context of human rights and international standards in this field. In respect to
      international and national humans and patients rights, regarding to achieve
      better quality of life, the governments should identify and determine the
      problems and obstacles that impede opioid use for medical purposes, in aim rich
      adequate pain relief for incurable patients. Implementation of newly adopted
      legislation in Georgia into practice will enable to overcome existing barriers;
      hence these patients will be able to pass their last path of life under care, as
      much as possible without pain and with dignity.

PMID- 20157213
TI  - Study of potential cytoprotective activity of different antioxidants.
AB  - It is known that infiltration of atherosclerotic plaques by activated T
      lymphocytes occurs at the early stage and cytokines produced by those lymphocytes
      become actively involved in inflammatory process. Consequently the preparations,
      capable of stabilization of immune cells, perhaps will be effective for treatment
      and prevention of atherosclerosis. Intensively proliferated Jurkat leukemic T
      cell line (human leukemic cell culture) is widely used in scientific and
      Therapeutic research, as human T lymphocyte pattern. The aim of the study--To
      establish the cytoprotective action of different antioxidative preparations on
      Jurkat cells incubated in oxidative stress conditions. It was revealed the dose
      (100 microl, 50 microl) and time-related decrease of viability of Jurkat cells
      incubated in high oxidative stress conditions. Low doses of hydrogen peroxide
      (H(2)O(2)) (25 microl, 11 microl) present cytotoxicity only within short terms (8
      hours). Vitamins C and E have cytotoxic effects on intact Jurkat cells
      separately; the activity of Megavite and Phenovin is not characterised by
      cytotoxicity. Incubation of Jurkat cells with antioxidants in moderate oxidative
      stress condition (H(2)O(2) 25 microl, 50 microl) all antioxidative preparations
      (except vitamin C) reveal static activity on viability of Jurkat cells.
      Incubation of Jurkat cells with antioxidants in intensive oxidative stress
      condition (H(2)O(2) 100 microl), the cytoprotective activity of antioxidative
      preparations was rather low.

PMID- 20157214
TI  - Molecular biology in prostate cancer.
AB  - Prostate cancer has become one of the most frequently diagnosed tumors in men and
      is one of the leading causes of death in men over 50 years old. Due to the
      development of molecular biology techniques used in recent prostate cancer
      studies, many new aspects of the disease are being discovered and may help in
      diagnosis, treatment and even to establish prognosis for these patients.
      Therefore, despite not yet common in clinical practice, several molecular biology
      techniques frequently need to be discussed with other physicians and even with
      the patient. In this article, we review some of the most important tools used in
      molecular biology and their recent discoveries in the study of prostate cancer.

PMID- 20157215
TI  - Primary retroperitoneal tumors: review of our 10-year case series.
AB  - OBJECTIVES: To investigate our case series of patients with primary
      retroperitoneal tumors over the past 10 years, analyzing clinical symptoms,
      diagnostic tests, tumor pathology, surgical data, concomitant cancer treatments,
      recurrence and survival rates. METHODS: Retrospective analysis of 37 patients
      with primary retroperitoneal tumors diagnosed at our hospital over the past 10
      years. RESULTS: Computed tomography (CT) was the imaging technique used most
      often and the most accurate. Tumors were malignant in 83% of patients and benign
      in 17%. Complete tumor resection was performed in 73% of cases; the most common
      approach was midline laparotomy. Neighboring organs were also removed in 51.8% of
      cases in which radical resection was performed. The recurrence rate was 45% in
      patients who underwent surgery. Median time to onset of recurrence following open
      surgery was 23 months. Repeat resection was performed in 66% of cases with
      recurrence. Five-year survival following total resection of malignant tumors was
      44%. The mean patient survival after repeat resection was 9.8 months.
      CONCLUSIONS: Primary retroperitoneal tumors are rare and usually malignant.
      Surgery is the treatment of choice and complete tumor resection is the main
      factor that determines prognosis.

PMID- 20157216
TI  - Immunomagnetic quantification of circulating tumoral cells in patients with
      prostate cancer: clinical and pathological correlation.
AB  - OBJECTIVES: To detect and enumerate circulating prostatic tumor cells (CTC) in
      the peripheral blood of patients with prostate cancer (PC) and study the
      relationship between CTCs and clinical-pathological parameters. METHODS:
      Prospective three-arm study: 26 patients (p) with localised PC (LPC); 24 P with
      metastatic PC (MPC) and 30 healthy volunteer controls. A single 7.5 ml sample of
      peripheral blood was retrieved; CTCs were isolated using an immunomagnetic method
      based on the CellSearch system (Veridex). CTCs were identified as nucleated cells
      negative for CD45 (leukocytes) and positive for cytokeratins. (8, 18 y 19) The
      relationship between CTC numbers and PSA levels, Gleason score and TNM
      classification was studied. RESULTS: Only 10% of the healthy controls had 1
      CTC/7.5 mL, none of the patients with localised PC had more than 3 CTCs (88% < or
      = 2 CTCs), and patients with MPC had significantly higher CTC levels [m: 29 (1
      178)] compared with the other two groups (P: 0.000). A positive correlation was
      demonstrated between the CTC count and PSA levels, tumor size, and presence or
      absence of enlarged lymph nodes. Gleason score was the only parameter that did
      not show any correlation with CTC levels, and although the number of CTCs was
      higher in patients with visceral metastases [m: 297 (0-416)] compared with bone
      metastases patients [m: 68 (9.5-168)] , these differences were not significant.
      CONCLUSIONS: Immunomagnetic analysis permits CTCs to be enumerated in peripheral
      blood and could be a possible way to correctly stage and make a reasonable
      prognosis of metastatic disease.

PMID- 20157217
TI  - Renal lithiasis in patients with primary hyperparathyroidism. Evolution and
      treatment.
AB  - OBJECTIVES: The relationship between hyperparathyroidism and lithiasis is quite
      known, so the study of parathyroid glands is especially mandatory in the face of
      relapses. Our objective is to analyze both primary hyperparathyroidism (PHPT)
      associated with renal lithiasis and the evolution of this condition after
      parathyroidectomy, as well as to study factors associated with the presence of
      lithiasis or bone pathology, and carry out a review on bibliography. METHODS: We
      describe a retrospective study of a series comprising 287 cases of
      hyperparathyroidism: 237 of them were primary and the remaining 50, secondary. We
      have included: sex, age, evolution time and symptoms, diagnostic tests
      (biochemical, radiological and histological). Factors such as number of episodes
      prior to diagnosis and treatments were analyzed in patients with symptomatic
      lithiasis to know whether patients exhibited residual lithiasis after the
      management of calculi or whether patients underwent episodes after
      parathyroidectomy, or whether or not they were treated. Statistical analysis was
      carried out through SPSS 15.0 for Windows. RESULTS: Forty five percent of the
      patients had suffered lithiasis episodes; 50%, osteopenia/osteoporosis; 23%,
      musculoskeletal pain; 23%, asthenia and/or depressive syndrome. In 13.5% of
      cases, diagnosis was supported by the presence of hypercalcemia; no other
      symptoms were detected. We have analyzed factors that favor or inhibit renal
      lithiasis formation and compared biochemical parameters from the group of primary
      hyperthyroidism that exhibited lithiasis (41 patients) with those patients who
      did not (49). We noted that lithiasis patients showed higher values of calcium,
      alkaline phosphatase, intact PTH, mean PTH, osteocalcin, and chlorine/phosphate,
      calciuria and phosphaturia indexes. Student's t test on two independent samples
      revealed significant statistical differences in calcium levels (p<0.05), intact
      PTH (<.05) and osteocalcin. CONCLUSIONS: Primary hyperparathyroidism patients
      with lithiasis presented higher values of parathormone, alkaline phosphatase,
      osteocalcin, and Cl/P and calciuria indexes than lithiasis-free PHPT patients.
      These patients exhibit objective improvement of symptoms after parathyroidectomy,
      and rarely a recurrence of lithiasis, a factor that generally coincides with
      persistence of residual lithiasis.

PMID- 20157218
TI  - Solifenacin pharmacology.
AB  - Antimuscarinics are the drugs of choice for the treatment of overactive bladder
      syndrome, and their benefit/risk ratio depends largely on selectivity for the
      different subtypes of muscarinic receptors. Solifenacin is the antimuscarinic
      that presents greatest selectivity for M3 bladder receptors, which may translate
      into a lower incidence of undesirable effects related to other receptor subtypes.
      Metabolic pathways of the antimuscarinics may impact efficacy and appearance of
      interactions. Solifenacin is metabolized only by the CYP3A4, giving three
      inactive metabolites and one with a similar activity to the original compound.
      However, other drugs in the group are also a substrate for the CYP 2D6 which
      presents polymorphisms, whereby their pharmacokinetics may be modified in slow
      metabolizers. The risk of interactions of solifenacin is low, and it is lower
      than that of the antimuscarinics which are also metabolized by the CYP 2D6. The
      unaltered fraction of solifenacin which is eliminated in urine, together with the
      active metabolite, can contribute to the therapeutic effect by acting on the
      urothelium receptors. It is not necessary to adjust doses of solifenacin in
      elderly patients or those with moderate liver or kidney impairment.

PMID- 20157219
TI  - Current definition and treatment of premature ejaculation.
AB  - OBJECTIVES: To discuss a concept about the current definition and treatment of
      premature ejaculation. METHODS: A detailed review was performed on the current
      definition and treatment of premature ejaculation. RESULTS: Several definitions
      were found, however a consensus on how to define premature ejaculation is
      lacking. In addition, there are several treatments: daily, on demand and topical
      agents. CONCLUSIONS: Premature ejaculation implicated three specific
      characteristics: short intravaginal ejaculatory latency time, lack of control,
      and sexual dissatisfaction.

PMID- 20157220
TI  - Laparoscopic heminefrectomy for crossed fused kidney with inferior ectopia.
AB  - OBJECTIVES: Crossed fused renal ectopia is a rare congenital anomaly. We report
      the case of a 3 year old boy with diagnosis of right crossed fused renal ectopia,
      history of recurrent urinary tract infection and previous failure of surgical
      treatment. METHODS: Three year old boy with diagnosis of right crossed fused
      renal ectopia of the inferior moiety underwent a laparoscopic heminephrectomy of
      the inferior renal unit, due to severe hydronephrosis and recurrent urinary tract
      infections. RESULTS: A laparoscopic right heminephrectomy of the inferior renal
      moiety was performed uneventfully. Operation room time was 200 minutes and there
      were no perioperative complications. Patient was discharged 18 hours after the
      procedure. After 5 years of follow up patient remains asymptomatic with good
      renal function. CONCLUSIONS: The laparoscopic approach is an acceptable option to
      treat this anomaly, with all the advantages of minimally invasive surgery.

PMID- 20157221
TI  - Nephron-sparing surgery: our experience in open and laparoscopic approach in 254
      cases.
AB  - OBJECTIVES: The majority of renal cell carcinomas are now incidentally detected
      as small renal masses in asymptomatic patients due to the widespread use of
      ultrasound and new improved noninvasive abdominal imaging modalities. Nephron
      sparing surgery is the treatment of choice for patients with small renal masses
      in presence of normal contralateral kidney or in presence of an anatomic or
      functional solitary kidney. We reviewed retrospectively our experience in open
      and laparoscopic partial nephrectomy. METHODS: The records for all patients who
      underwent nephron-sparing surgery for a renal mass since 1995 at British Hospital
      of Buenos Aires and Hospital Aleman and since 2000 at Hospital Universitario
      Austral were reviewed. The most relevant data of 246 patients were collected,
      with special focus on demographic data, operative details, pathology results,
      complications and outcome in cancer control. RESULTS: We have performed 254
      nephron-sparing surgeries. Open partial nephrectomy was performed in 220
      procedures and the laparoscopic partial nephrectomy since 2001 in 34 patients.
      The indication was elective or relative in 236 patients with 8 patients with
      bilateral tumors and 18 tumors in a solitary kidney. The pedicle was clamped in
      168 procedures with hypothermia in 43 patients. Mean ischemia time was 24.7
      minutes. Average tumor size was 3.49 cm. The pathologic findings demonstrate a
      carcinoma in 193 cases and benign lesions in 61 patients (24%). One patient
      presented a positive surgical margin in the pathologic examination, but
      subsequent nephrectomy was negative for residual tumor. One patient presented a
      pseudo-tumoral mass on follow-up on CT scan and MRI, but nephrectomy was negative
      for residual tumor. There were postoperative complications in 20 patients (7.9
      %). Oncologic follow up was available in 84% of the patients for an average of
      46.6 months showing progression with metastasis in 8 patients. Local recurrence
      was observed in 4 patients (2%). One patient developed a tumor in the
      contralateral kidney 20 months after partial nephrectomy and another one 10 years
      later. The cancer specific survival and overall survival rates were 98 % and 95%
      respectively. In the last year the laparoscopic approach duplicated the
      indications of all previous years. CONCLUSIONS: Open partial nephrectomy is
      considered nowadays the gold standard treatment of small renal masses, and in our
      experience it is a safe and effective technique of treatment of these tumors. The
      evolution of the technology and the acquirement of laparoscopic skills allow us
      in selected cases to duplicate the open approach in a laparoscopic way, obtaining
      similar results.

PMID- 20157222
TI  - Leiomyoma of the male urethra: case report and review of the literature.
AB  - OBJECTIVES: Case report of a 5 cm. male urethral leiomyoma (UL). METHOD: UL is
      extremely rare entity, with only seven cases in the literature. Its etiology is
      still unknown. Leiomyoma may be present in several locations inside the urinary
      tract. When located in the urethra it usually produces obstructive symptoms, but
      also may have asymptomatic behavior. Definitive diagnosis requires histological
      confirmation. Intraurethral neoplasms must be included in the differential
      diagnosis. RESULTS: Patient is free of lower urinary tract symptoms after
      complete excision of his urethral leiomyoma. CONCLUSIONS: Indication and surgical
      approach depend on tumor and size location. Prognostic is excellent after
      surgical removal.

PMID- 20157223
TI  - Renocolic fistula as a complication of radiofrequency in the treatment of renal
      cell carcinoma.
AB  - METHOD: Beyond postoperative suspicion, retrograde pyelogram was performed, the
      images of which are displayed, and demonstrated the fistula. RESULTS: Treatment
      has been definitive nephrectomy after failed attempt to seal the fistula with
      suture and TachoSil. CONCLUSIONS: Although radiofrequency ablation can be a valid
      technique for treating small renal tumors in patients with high morbidity, it is
      not without significant complications as described in this case, despite the
      precautions taken.

PMID- 20157224
TI  - Hair receptor sensitivity to changes in laminar boundary layer shape.
AB  - Biologists have shown that bat wings contain distributed arrays of flow-sensitive
      hair receptors. The hair receptors are hypothesized to feedback information on
      airflows over the bat wing for enhanced stability or maneuverability during
      flight. Here, we study the geometric specialization of hair-like structures for
      the detection of changes in boundary layer velocity profiles (shapes). A quasi
      steady model that relates the flow velocity profile incident on the longitudinal
      axis of a hair to the resultant moment and shear force at the hair base is
      developed. The hair length relative to the boundary layer momentum thickness that
      maximizes the resultant moment and shear-force sensitivity to changes in boundary
      layer shape is determined. The sensitivity of the resultant moment and shear
      force is shown to be highly dependent on hair length. Hairs that linearly taper
      to a point are shown to provide greater output sensitivity than hairs of uniform
      cross-section. On an order of magnitude basis, the computed optimal hair lengths
      are in agreement with the range of hair receptor lengths measured on individual
      bat species. These results support the hypothesis that bats use hair receptors
      for detecting changes in boundary layer shape and provide geometric guidelines
      for artificial hair sensor design and application.

PMID- 20157227
TI  - On the p(dis) correction factor for cylindrical chambers.
AB  - The authors of a recent paper (Wang and Rogers 2009 Phys. Med. Biol. 54 1609)
      have used the Monte Carlo method to simulate the 'classical' experiment made more
      than 30 years ago by Johansson et al (1978 National and International
      Standardization of Radiation Dosimetry (Atlanta 1977) vol 2 (Vienna: IAEA) pp 243
      70) on the displacement (or replacement) perturbation correction factor p(dis)
      for cylindrical chambers in 60Co and high-energy photon beams. They conclude that
      an 'unreasonable normalization at dmax' of the ionization chambers response led
      to incorrect results, and for the IAEA TRS-398 Code of Practice, which uses
      ratios of those results, 'the difference in the correction factors can lead to a
      beam calibration deviation of more than 0.5% for Farmer-like chambers'. The
      present work critically examines and questions some of the claims and generalized
      conclusions of the paper. It is demonstrated that for real, commercial Farmer
      like chambers, the possible deviations in absorbed dose would be much smaller
      (typically 0.13%) than those stated by Wang and Rogers, making the impact of
      their proposed values negligible on practical high-energy photon dosimetry.
      Differences of the order of 0.4% would only appear at the upper extreme of the
      energies potentially available for clinical use (around 25 MV) and, because lower
      energies are more frequently used, the number of radiotherapy photon beams for
      which the deviations would be larger than say 0.2% is extremely small. This work
      also raises concerns on the proposed value of pdis for Farmer chambers at the
      reference quality of 60Co in relation to their impact on electron beam dosimetry,
      both for direct dose determination using these chambers and for the cross
      calibration of plane-parallel chambers. The proposed increase of about 1% in
      p(dis) (compared with TRS-398) would lower the kQ factors and therefore Dw in
      electron beams by the same amount. This would yield a severe discrepancy with the
      current good agreement between electron dosimetry based on an electron cross
      calibrated plane-parallel chamber (against a Farmer) or on a directly 60Co
      calibrated plane-parallel chamber, which is not likely to be in error by 1%. It
      is suggested that the influence of the 60Co source spectrum used in the
      simulations may not be negligible for calculations aimed at an uncertainty level
      of 0.1%.

PMID- 20157226
TI  - Acceleration of the direct reconstruction of linear parametric images using
      nested algorithms.
AB  - Parametric imaging using dynamic positron emission tomography (PET) provides
      important information for biological research and clinical diagnosis. Indirect
      and direct methods have been developed for reconstructing linear parametric
      images from dynamic PET data. Indirect methods are relatively simple and easy to
      implement because the image reconstruction and kinetic modeling are performed in
      two separate steps. Direct methods estimate parametric images directly from raw
      PET data and are statistically more efficient. However, the convergence rate of
      direct algorithms can be slow due to the coupling between the reconstruction and
      kinetic modeling. Here we present two fast gradient-type algorithms for direct
      reconstruction of linear parametric images. The new algorithms decouple the
      reconstruction and linear parametric modeling at each iteration by employing the
      principle of optimization transfer. Convergence speed is accelerated by running
      more sub-iterations of linear parametric estimation because the computation cost
      of the linear parametric modeling is much less than that of the image
      reconstruction. Computer simulation studies demonstrated that the new algorithms
      converge much faster than the traditional expectation maximization (EM) and the
      preconditioned conjugate gradient algorithms for dynamic PET.

PMID- 20157228
TI  - An investigation of the potential of optical computed tomography for imaging of
      synchrotron-generated x-rays at high spatial resolution.
AB  - X-ray microbeam radiation therapy (MRT) is a novel form of treatment, currently
      in its preclinical stage, which uses microplanar x-ray beams from a synchrotron
      radiation source. It is important to perform accurate dosimetry on these
      microbeams, but, to date, there has been no accurate enough method available for
      making 3D dose measurements with isotropic, high spatial resolution to verify the
      results of Monte Carlo dose simulations. Here, we investigate the potential of
      optical computed tomography for satisfying these requirements. The construction
      of a simple optical CT microscopy (optical projection tomography) system from
      standard commercially available hardware is described. The measurement of optical
      densities in projection data is shown to be highly linear (r2=0.999). The depth
      of-field (DOF) of the imaging system is calculated based on the previous
      literature and measured experimentally using a commercial DOF target. It is shown
      that high quality images can be acquired despite the evident lack of
      telecentricity and despite DOF of the system being much lower than the sample
      diameter. Possible reasons for this are discussed. Results are presented for a
      complex irradiation of a 22 mm diameter cylinder of the radiochromic polymer
      PRESAGE, demonstrating the exquisite 'dose-painting' abilities available in the
      MRT hutch of beamline ID-17 at the European Synchrotron Radiation Facility. Dose
      distributions in this initial experiment are equally well resolved on both an
      optical CT scan and a corresponding transmission image of radiochromic film, down
      to a line width of 83 microm (6 lp mm(-1)) with an MTF value of 0.40. A group of
      33 microm wide lines was poorly resolved on both the optical CT and film images,
      and this is attributed to an incorrect exposure time calculation, leading to
      under-delivery of dose. Image artefacts in the optical CT scan are discussed.
      PRESAGE irradiated using the microbeam facility is proposed as a suitable
      material for producing phantom samples for quantitative characterization of
      optical CT microscopy systems.

PMID- 20157229
TI  - SAR calculations from 20 MHz to 6 GHz in the University of Florida newborn voxel
      phantom and their implications for dosimetry.
AB  - This paper presents finite-difference time-domain (FDTD) calculations of SAR in
      the University of Florida newborn female model. The newborn model is based upon a
      surface representation of the organs of the body, using non-uniform rational B
      spline surfaces (NURBS). The surface model can then be converted into voxels at
      any resolution required. This flexibility allows the preparation of voxel models
      at 2, 1 and 0.5 mm to investigate the effect of resolution on dispersion and the
      choice of algorithms to calculate SAR in the Yee cell as the frequency increases
      up to 6 GHz. The added advantage of the newborn model is that it is relatively
      small and so FDTD calculations can be made tractable at a very fine resolution of
      0.5 mm. A comparison is made between the calculated external electric fields
      required to produce the basic restriction on whole-body-averaged SAR and the
      ICNIRP reference levels for public exposure. At 250 MHz, the whole body
      resonance, the ICNIRP reference level does not provide a conservative estimate of
      the whole-body-averaged SAR restriction. The reference level is also breached in
      the range 700-2450 MHz by all of the irradiation geometries considered.

PMID- 20157230
TI  - Extension of the NCAT phantom for the investigation of intra-fraction respiratory
      motion in IMRT using 4D Monte Carlo.
AB  - The purpose of this work was to create a computational platform for studying
      motion in intensity modulated radiotherapy (IMRT). Specifically, the non-uniform
      rational B-spline (NURB) cardiac and torso (NCAT) phantom was modified for use in
      a four-dimensional Monte Carlo (4D-MC) simulation system to investigate the
      effect of respiratory-induced intra-fraction organ motion on IMRT dose
      distributions as a function of diaphragm motion, lesion size and lung density.
      Treatment plans for four clinical scenarios were designed: diaphragm peak-to-peak
      amplitude of 1 cm and 3 cm, and two lesion sizes--2 cm and 4 cm diameter placed
      in the lower lobe of the right lung. Lung density was changed for each phase
      using a conservation of mass calculation. Further, a new heterogeneous lung model
      was implemented and tested. Each lesion had an internal target volume (ITV)
      subsequently expanded by 15 mm isotropically to give the planning target volume
      (PTV). The PTV was prescribed to receive 72 Gy in 40 fractions. The MLC leaf
      sequence defined by the planning system for each patient was exported and used as
      input into the MC system. MC simulations using the dose planning method (DPM)
      code together with deformable image registration based on the NCAT deformation
      field were used to find a composite dose distribution for each phantom. These
      composite distributions were subsequently analyzed using information from the
      dose volume histograms (DVH). Lesion motion amplitude has the largest effect on
      the dose distribution. Tumor size was found to have a smaller effect and can be
      mitigated by ensuring the planning constraints are optimized for the tumor size.
      The use of a dynamic or heterogeneous lung density model over a respiratory cycle
      does not appear to be an important factor with a <or=0.6% change in the mean dose
      received by the ITV, PTV and right lung. The heterogeneous model increases the
      realism of the NCAT phantom and may provide more accurate simulations in
      radiation therapy investigations that use the phantom. This work further
      evaluates the NCAT phantom for use as a tool in radiation therapy research in
      addition to its extensive use in diagnostic imaging and nuclear medicine
      research. Our results indicate that the NCAT phantom, combined with 4D-MC
      simulations, is a useful tool in radiation therapy investigations and may allow
      the study of relative effects in many clinically relevant situations.

PMID- 20157231
TI  - Improving the performance of the signal space separation method by comprehensive
      spatial sampling.
AB  - Biomagnetic instruments usually employ sensors with approximately radial normal
      vectors arranged on a near-spherical surface. The multipole expansion employed in
      the recently introduced signal space separation method (SSS) reveals limitations
      in this traditional sensor array design. Specifically, we show that the excessive
      symmetry of the sensor array impedes separation of multipole components arising
      from inside and outside of the array. This motivates consideration of novel
      instrument designs that would sample the field in a more comprehensive way. We
      evaluated several simulated sensor arrays that employ vector sensors in one or
      two layers, giving information on multiple field components and the radial
      dependence of the field. Our results indicate that this kind of sensor array
      design could significantly improve SSS performance, leading to enhanced shielding
      against external interference and reduced noise after signal reconstruction. The
      best two-layer array evaluated here attains a shielding factor of nearly 1000 or
      60 dB with about 400 sensors. Due to limited spatial coverage, a traditional
      reference array geometry does not give the same level of improvement. In addition
      to improved software shielding, enhanced detection of different multipole
      components increases the information obtained about the magnetic field, which has
      fundamental importance.

PMID- 20157232
TI  - Facile synthesis of monodisperse, size-tunable SnS nanoparticles potentially for
      solar cell energy conversion.
AB  - A simple strategy to synthesize monodisperse, single-crystalline and size-tunable
      SnS nanoparticles was reported. An active sulfur precursor
      bis(trimethylsilyl)sulfide was applied to enable fast nucleation of tin species
      in oleylamine. As-synthesized nanoparticles were easily dispersed in a non-polar
      organic solvent and formed a uniform solution which showed complete absorption of
      visible light. The smooth, dense-packed and crack-free SnS film was achieved by
      spin-coating that showed an enhanced photoresponse via methanol treatment. Owing
      to their noble merits, as-synthesized SnS nanoparticles could be a potential
      nanomaterial for solar cell application.

PMID- 20157233
TI  - Hybrid solar cells based on single-walled carbon nanotubes/Si heterojunctions.
AB  - Photovoltaic devices based on single-walled carbon nanotubes (SWNTs) and n
      silicon heterojunctions have been fabricated by a spray deposition process. We
      provide direct evidence that nanotubes serve as an active photosensing material
      involved directly in the photon absorption process as well as contributing to
      charge separation, transport and collection. The characteristic band of the SWNT
      band in the photoconductivity spectrum matches the S(11) absorption band of
      semiconducting SWNTs of 7,6 chirality. Centrifugation of the SWNTs provides two
      fractions. The sediment fraction exhibits a conversion efficiency ( approximately
      1.7%) higher by a factor of eight compared to the supernatant fraction. SEM
      images and conductivity measurements show that the SWNT network morphology of the
      sediment fraction has longer and thicker nanotube bundles forming highly porous
      films, accounting for the enhanced conductivity and higher transparency.

PMID- 20157234
TI  - Time-resolved photoluminescence investigations on HfO2-capped InP nanowires.
AB  - We have employed time-resolved photoluminescence (PL) spectroscopy to study the
      impact of HfO(2) surface capping by atomic layer deposition (ALD) on the optical
      properties of InP nanowires (NWs). The deposition of high-kappa dielectrics
      acting as a gate oxide is of particular interest in view of possible applications
      of semiconductor NWs in future wrap-gated field effect transistors (FETs). A high
      number of charged states at the NW-dielectrics interface can strongly degrade the
      performance of the FET which explains the strong interest in high quality
      deposition of high-kappa dielectrics. In the present work we show that time
      resolved spectroscopy is a valuable and direct tool to monitor the surface
      quality of HfO(2)-capped InP NWs. In particular, we have studied the impact of
      ALD process parameters as well as surface treatment prior to the oxide capping on
      the NW-dielectrics interface quality. The best results in terms of the surface
      recombination velocity (S(0) = 9.5 x 10(3) cm s(-1)) were obtained for InP/GaP
      core/shell NWs in combination with a low temperature (100 degrees C) ALD process.
      While the present report focuses on the InP material system, our method of
      addressing the surface treatment for semiconductors with high-kappa dielectrics
      will also be applicable to nanoelectronic devices based on other III/V material
      systems such as InAs.

PMID- 20157236
TI  - Antisaccades: a probe into the dorsolateral prefrontal cortex in Alzheimer's
      disease. A critical review.
AB  - The number of people living with Alzheimer's disease (AD), the major cause of
      dementia, is projected to increase dramatically over the next few decades, making
      the search for treatments and tools to measure the progression of AD increasingly
      urgent. The antisaccade task, a hands- and language-free measure of inhibitory
      control, has been utilized in AD as a potential diagnostic test. While
      antisaccades do not appear to differentiate AD from healthy aging better than
      measures of episodic memory, they may still be beneficial. Specifically,
      antisaccades may provide not only a functional index of the Dorsolateral
      Prefrontal Cortex (DLPFC), which is damaged in the later stages of AD, but also a
      tool for monitoring the progression of AD. Further work is required to: 1)
      strengthen the link between antisaccade errors, in AD, with the DLPFC; 2) insure
      that antisaccade errors do not result from memory, visuospatial, or other
      deficits associated with AD; and 3) further validate the clinical analogue of the
      antisaccade task.

PMID- 20157235
TI  - Genetics of psychosis in Alzheimer's disease: a review.
AB  - In and of itself, late-onset Alzheimer's disease (AD) can be a devastating
      illness. However, a sub-group of AD patients develop psychosis as the disease
      progresses. These patients have an added burden of greater cognitive impairment,
      higher rates of institutionalization, and higher mortality than AD patients
      without psychosis. While the etiopathogenesis such as psychosis in AD (AD+P) is
      not known, mounting evidence accrued over the past ten years indicates that AD+P
      represents a distinct phenotype with a genetic basis. Elucidating the genetic
      mechanism of AD+P is crucial if better pharmaceutical treatments are to be
      developed for these patients. The goal of this review is to summarize what is
      currently known regarding the genetic basis of psychosis in AD. Specific
      attention is given to familial aggregation and heritability, linkage to
      chromosomal loci, and associations of candidate genes of APOE and the monoamine
      neurotransmitter system.

PMID- 20157237
TI  - A flavonol glycoside, isolated from roots of Panax notoginseng, reduces amyloid
      beta-induced neurotoxicity in cultured neurons: signaling transduction and drug
      development for Alzheimer's disease.
AB  - A Radix Notoginseng flavonol glycoside (RNFG), quercetin 3-O-beta-D-xylopyranosyl
      beta-D-galactopyranoside, was isolated from roots of Panax notoginseng. Among
      different biological properties tested, RNFG possessed a strong activity in
      preventing amyloid-beta (Abeta)-induced cell death. In an in vitro assay, RNFG
      inhibited the aggregation of Abeta in a dose-dependent manner. Moreover,
      application of RNFG in cultured cortical neurons, or PC12 cells, reduced the
      Abeta-induced cell death in time- and dose-dependent manners, with the
      suppression of Abeta-induced DNA fragmentation and caspase-3 activation. In
      cultured neurons, the pre-treatment of RNFG abolished the increase of Ca(2+)
      mobilization triggered by Abeta. The neuroprotective properties of RNFG required
      a specific sugar attachment within the main chemical backbone because the
      flavonol backbone by itself did not show any protective effect. In memory
      impairment experiments using the passive avoidance task, the administration of
      RNFG reduced brain damage in scopolamine-treated rats. These results therefore
      reveal a novel function of Radix Notoginseng and its flavonol glycoside that
      could be very useful in developing food supplements for the prevention, or
      potential treatment, of Alzheimer's disease.

PMID- 20157238
TI  - Neuroprotective effects of polysaccharides from wolfberry, the fruits of Lycium
      barbarum, against homocysteine-induced toxicity in rat cortical neurons.
AB  - Previous clinical and epidemiological studies have suggested that elevated plasma
      homocysteine (Hcy) levels increased the risk of Alzheime's disease (AD). Although
      the underlying mechanisms of its toxicity are elusive, it has been shown that Hcy
      damages neurons by inducing apoptosis, DNA fragmentation, and tau
      hyperphosphorylation. Wolfberry (Lycium barbarum) is a fruit that is known for
      its eye-protective and anti-aging properties in Asian countries. Previous studies
      from our laboratory have demonstrated that polysaccharides derived from wolfberry
      (LBA) have the ability to protect neurons from amyloid-beta (Abeta) peptide
      neurotoxicity. We hypothesize that the neuroprotective effects of wolfberry is
      not limited to Abeta and can also provide protection against other AD risk
      factors. In this study, we aim to elucidate the neuroprotective effects of
      wolfberry against Hcy-induced neuronal damage. Our data showed that LBA treatment
      significantly attenuated Hcy-induced neuronal cell death and apoptosis in primary
      cortical neurons as demonstrated by LDH and caspase-3 like activity assay. LBA
      also significantly reduced Hcy-induced tau phosphorylation at tau-1
      (Ser198/199/202), pS396 (Ser396), and pS214 (Ser214) epitopes as well as cleavage
      of tau. At the same time, we also found that the phosphorylation level of p
      GSK3beta (Ser9/Tyr 216) remained unchanged among different treatment groups at
      all detected time points. LBA treatment suppressed elevation of both p-ERK and p
      JNK. In summary, our data demonstrated that LBA exerted neuroprotective effects
      on cortical neurons exposed to Hcy. Therefore, LBA has the potential to be a
      diseasemodifying agent for the prevention of AD.

PMID- 20157239
TI  - Upregulation of cytoplasmic gelsolin, an amyloid-beta-binding protein, under
      oxidative stress conditions: involvement of protein kinase C.
AB  - We have previously reported that gelsolin, an actin binding protein, regulates
      the fibrillization of amyloid-beta protein. We report here that the expression of
      cytoplasmic gelsolin (cgelsolin) was upregulated in a concentration-dependent
      manner when SH-SY5Y, PC-12, and HEK-293 cells were subjected to oxidative stress
      by treatment with hydrogen peroxide (H(2)O(2). Further studies were done to
      elucidate the mechanism involved in the regulation of c-gelsolin expression in
      cells. Pretreatment of cells with cycloheximide (an inhibitor of protein
      synthesis) resulted in significant inhibition of H(2)O(2)induced c-gelsolin
      expression, suggesting the possible de novo synthesis of c-gelsolin in cells.
      Staurosporine, a potent inhibitor of a variety of protein kinases including
      protein kinase C (PKC), also blocked the H(2)O(2)induced expression of cgelsolin.
      However, both H(2)O(2) and staurosporine activated the mitogen-activated protein
      kinases (MAPKs), i.e., c-Jun N-terminal kinase, P38, and extracellular signal
      regulated kinase. Pretreatment of cells with Calphostin C, an inhibitor of PKC,
      blocked the upregulation of cgelsolin induced by H(2)O(2), while specific
      inhibitors of MAPKs had no effect on c-gelsolin expression, suggesting that MAPKs
      may not be involved in H(2)O(2)mediated upregulation of cgelsolin. On the other
      hand, phorbol-12-myristate-13-acetate, an activator of PKC, induced the
      expression of c-gelsolin. Our studies indicate that c-gelsolin is upregulated in
      cells under oxidative stress, and PKC is involved in its upregulation. It is
      suggested that activators of PKC that induce gelsolin expression may have
      therapeutic significance in Alzheimer's disease.

PMID- 20157240
TI  - Relationship between cortisol levels and memory performance may be modulated by
      the presence or absence of cognitive impairment: evidence from healthy elderly,
      mild cognitive impairment and Alzheimer's disease subjects.
AB  - An inverted U-shape function between cortisol levels and memory performance has
      been reported in studies on both young animals and humans. Yet little is known
      about this relationship in normal aging or in older subjects with cognitive
      impairment. This issue is particularly significant since increased levels of
      cortisol have been reported in Alzheimer's disease (AD). The present study
      examined the association between cortisol levels and visual memory performance in
      healthy subjects as well as in individuals presenting mild cognitive impairment
      (MCI) or AD. Salivary cortisol was measured in 40 healthy elderly subjects, 31
      individuals with amnestic MCI, and 40 subjects with mild probable AD. Memory
      performance was evaluated using the Brief Cognitive Screening Battery. Higher
      cortisol levels were associated with better memory performance in healthy elderly
      (p=0.005), while higher cortisol levels were correlated with poorer memory
      performance in MCI subjects (p=0.011). No correlation between cortisol and memory
      was found in the AD group (p > 0.05). These results suggest that the relationship
      between cortisol levels and memory performance in the aging process could vary
      according to the presence or absence of cognitive impairment.

PMID- 20157242
TI  - Global functional coupling of resting EEG rhythms is related to white-matter
      lesions along the cholinergic tracts in subjects with amnesic mild cognitive
      impairment.
AB  - We tested the hypothesis that global functional coupling of resting cortical
      electroencephalographic (EEG) rhythms is abnormal in amnesic mild cognitive
      impairment (MCI) patients with remarkable lesions along the cholinergic white
      matter tracts. We used the eyes-closed resting EEG data (10-20 montage) of the
      same groups of 28 healthy elderly (Nold) and 57 MCI subjects of a previous
      reference study. The estimation of the cholinergic lesion was performed with a
      validated semi-automatic algorithm based on fluid-attenuated inversion recovery
      sequences on MRI. The MCI patients were divided into groups of high (MCI+; n=28)
      and low (MCI-; n=29) cholinergic damage. EEG rhythms of interest were delta (2-4
      Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz),
      beta2 (20-30 Hz), and gamma (30- 40 Hz). The global functional coupling of the
      EEG rhythms was indexed computing the spectral coherence between each electrode
      and the other 18 electrodes ("electrode" coherence) and then averaging the
      "electrode" coherence of all 19 electrodes (total coherence). Total coherence of
      alpha1 rhythms was highest in the Nold, intermediate in the MCI-, and lowest in
      the MCI+ groups. Furthermore, the alpha1 total coherence was negatively
      correlated to (moderate to high) cholinergic lesion across the MCI subjects. In
      conclusion, damage to the cholinergic system is associated with alterations of
      the functional global coupling of resting alpha rhythms.

PMID- 20157241
TI  - Cholinesterase activity and mRNA level of nicotinic acetylcholine receptors
      (alpha4 and beta2 Subunits) in blood of elderly Chinese diagnosed as Alzheimer's
      disease.
AB  - The aim of the study is to investigate the cholinergic deficit in Alzheimer's
      disease (AD) and identify candidate blood biomarkers for the diagnosis of the
      disease. Twenty-nine elderly Chinese diagnosed with AD and 33 age-matched
      controls were selected. The activities of acetylcholinesterase (AChE) and
      butyrylcholinesterase (BuChE) in plasma were detected by a spectrophotometric
      method, and the mRNA levels of alpha4 and beta2 nicotinic acetylcholine receptor
      (nAChR) subunits in blood leukocytes were analyzed by reverse transcriptase
      polymerase chain reaction (RT-PCR). The results showed that AChE activity in
      plasma was significantly lower in the AD group than in normal controls, while
      BuChE activity did not show any differences between AD and controls; mRNA levels
      of both alpha4 and beta2 nAChR subunits in blood leukocytes were significantly
      lower in the AD group than in controls. The AChE activity and the mRNA levels of
      alpha4 and beta2 nAChR subunits in the AD patients were also significantly
      correlated with cognitive test scores. No differences of AChE in plasma or alpha4
      and beta2 nAChR subunits in blood leukocytes were detected between smoking and
      non-smoking subjects. The results indicated that the decreases in the activity of
      AChE and in the mRNA levels of nAChR alpha4 and beta2 subunits from the
      peripheral blood of patients with AD might serve as supplementary indicators for
      the clinical diagnosis of AD.

PMID- 20157243
TI  - Clinical-genetic correlations in familial Alzheimer's disease caused by
      presenilin 1 mutations.
AB  - We describe the clinical phenotype of nine kindred with presenile Alzheimer's
      disease (AD) caused by different presenilin 1 (PS1) point mutations, and compare
      them with reported families with mutations in the same codons. Mutations were in
      exon 4 (Phe105Val), exon 5 (Pro117Arg, Glu120Gly), exon 6 (His163Arg), exon 7
      (Leu226Phe), exon 8 (Val261Leu, Val272Ala, Leu282Arg), and exon 12 (Ile439Ser).
      Three of these amino acid changes (Phe105Val, Glu120Gly, and Ile439Ser) had not
      been previously reported. Distinct clinical features, including age of onset,
      symptoms and signs associated with the cortical-type dementia and aggressiveness
      of the disease, characterized the different mutations and were quite homogeneous
      across family members. Age of onset fell within a consistent range: some
      mutations caused the disease in the thirties (P117R, L226F, V272A), other in the
      forties (E120G, H163R, V261L, L282R), and other in the fifties (F105V, I439S).
      Associated features also segregated with specific mutations: early epileptic
      activity (E120G), spastic paraparesis (V261L), subcortical dementia and
      parkinsonism (V272A), early language impairment, frontal signs, and myoclonus
      (L226F), and late myoclonus and seizures (H163R, L282R). Neurological
      deterioration was particularly aggressive in PS1 mutations with earlier age of
      onset such as P117R, L226F, and E120G. With few exceptions, a similar clinical
      phenotype was found in families reported to have either the same mutation or
      different amino acid changes in the same codons. This series points to a strong
      influence of the specific genetic defect in the development of the clinical
      phenotype.

PMID- 20157245
TI  - B vitamin deficiency promotes tau phosphorylation through regulation of GSK3beta
      and PP2A.
AB  - Neurofibrillary tangles (NFTs), composed of intracellular filamentous aggregates
      of hyperphosphorylated protein tau, are one of the pathological hallmarks of
      Alzheimer's disease (AD). Tau phosphorylation is regulated by the equilibrium
      between activities of its protein kinases and phosphatases; unbalance of these
      activities is proposed to be a reasonable causative factor to the disease
      process. Glycogen synthase kinase 3beta (GSK3beta) is one of the most important
      protein kinase in regulating tau phosphorylation; overexpression of active
      GSK3beta causes ADlike hyperphosphorylation of tau. Protein phosphatase 2A (PP2A)
      is the major phosphatase that dephosphorylates tau; it was demonstrated that
      highly conserved carboxyl-terminal sequence of PP2A C-subunit is a focal point
      for phosphatase regulation. This is the site of a reversible methyl
      esterification reaction that controls AB<formula>_{alpha}</formula>C
      heterotrimers formation. Here we demonstrate that GSK3beta and PP2A genes were
      upregulated by inhibiting methylation reactions through B vitamin deficiency. In
      this condition, methylated catalytic subunit PP2Ac was decreased, leading to
      reduced PP2A activity. By contrast, we observed GSK3beta protein increase and a
      modulation in phosphorylation sites that regulate GSK3beta activity. Therefore,
      one-carbon metabolism alteration seems to be a cause of deregulation of the
      equilibrium between GSK3beta and PP2A, leading to abnormal hyperphosphorylated
      tau.

PMID- 20157246
TI  - The H1 haplotype of the tau gene (MAPT) is associated with mild cognitive
      impairment.
AB  - Mild cognitive impairment is often considered a transitional condition prodromal
      to Alzheimer's disease. The dissection of genetic risk factors predisposing to
      mild cognitive impairment is paramount to assess the individual predisposition
      and reliably evaluate the effectiveness of early therapeutic interventions. We
      designed a cross-sectional analysis to test whether the occurrence of mild
      cognitive impairment is influenced by variations of the tau protein gene. The
      genotypes of seven polymorphisms tagging the major tau haplotypes were assayed on
      186 patients with amnestic mild cognitive impairment and 191 unrelated controls.
      Association study was conducted by logistic regression including APOE genotype
      and age as covariates. Case-control analysis showed that the common H1 haplotype
      is significantly overrepresented in patients (OR, 95% CI: 2.31, 1.52-3.51;
      p<0.001), whereas did not provide positive signals for any of the H1 sub
      haplotypes that had been described as associated with Alzheimer inverted
      exclamation mark s disease. This finding was confirmed when the epsilon4 allele
      of the APOE gene was taken into account (OR, 95% CI: 2.319, 1.492-3.603;
      p<0.001). These results firstly suggest that the risk of mild cognitive
      impairment is influenced by tau protein gene variations and that mild cognitive
      impairment shares a common genetic background with Alzheimer's disease. They may
      help elucidating the genetic risk to cognitive decline and designing effective
      clinical trials.

PMID- 20157244
TI  - Cystatin C protects neuronal cells from amyloid-beta-induced toxicity.
AB  - Multiple studies suggest that cystatin C (CysC) has a role in Alzheimer's disease
      (AD) and a decrease in CysC secretion is linked to the disease in patients with a
      polymorphism in the CysC gene. CysC binds amyloid-beta (Abeta) and inhibits
      formation of Abeta fibrils and oligomers both in vitro and in mouse models of
      amyloid deposition. Here we studied the effect of CysC on cultured primary
      hippocampal neurons and a neuronal cell line exposed to either oligomeric or
      fibrillar cytotoxic forms of Abeta. The extracellular addition of the secreted
      human CysC together with preformed either oligomeric or fibrillar Abeta increased
      cell survival. While CysC inhibits Abeta aggregation, it does not dissolve
      preformed Abeta fibrils or oligomers. Thus, CysC has multiple protective effects
      in AD, by preventing the formation of the toxic forms of Abeta and by direct
      protection of neuronal cells from Abeta toxicity. Therapeutic manipulation of
      CysC levels, resulting in slightly higher concentrations than physiological could
      protect neuronal cells from cell death in AD.

PMID- 20157247
TI  - Amyloid-beta peptides stimulate the expression of the p75(NTR) neurotrophin
      receptor in SHSY5Y human neuroblastoma cells and AD transgenic mice.
AB  - The progression toward end-stage Alzheimer's disease (AD) in the aging brain is
      driven by accumulating amyloid-beta (Abeta)(1-42) oligomers that is accompanied
      by the downregulation of the Trk A neurotrophin receptor and by either
      upregulation or at least maintenance of the p75 neurotrophin receptor (p75(NTR)),
      which can be stimulated by the accumulating Abeta(1-42) peptides. Here we show
      that Abeta(1-42) and its active fragment Abeta(25-35), but not Abeta(42-1), can
      at least double the level of p75(NTR) receptors in the membranes of model SH-SY5Y
      human neuroblastoma cells. We also show that p75(NTR) is upregulated in the
      hippocampi of two strains of AD transgenic mice. Specifically, the level of the
      p75(NTR) receptor in the hippocampal membranes from 12-15 month old AD-triple
      transgenic mice (3xTg-AD) harboring PS1 (M146V), AbetaPP (Swe), and tau (P301L)
      was nearly twice that in hippocampal membranes from age-matched wild-type mice.
      Similarly, the level of p75 (NTR) receptor in 7 month-old B6.Cg-Tg AD mice
      harboring PSEN1dE9 and AbetaPP (Swe) was also increased above the level in the
      corresponding wild-type mice. This increase correlated with the age-dependent
      rise in Abeta(1-42) levels in the AD mice. Thus, it appears that it could be the
      accumulating Abeta(1-42) that increases or at least prevents the downregulation
      of p75 (NTR) receptors in key parts of AD brains. It is possible that when the
      Abeta (1-42) accumulation reaches a critical level in the brain on the way to
      late-onset AD, the Abeta (1-42) induced p75 (NTR) receptor signaling starts a
      vicious cycle that accelerates AD development because of the activated receptors'
      recently shown ability to stimulate Abeta(1-42) production.

PMID- 20157248
TI  - Multi-center study on Alzheimer's disease using FDG PET: group and individual
      analyses.
AB  - Using statistical parametric mapping (SPM), we evaluate the feasibility and
      accuracy of (18) F -2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography
      (PET) for clinical diagnosis with characteristic hypo-metabolic regions, and
      examine the consistency of cerebral hypo-metabolism in Alzheimer's disease (AD)
      cross multicenters at both the group and the individual levels. Four groups of
      scan data including 39 AD patients and 52 healthy control subjects derived from
      three centers were analyzed and comparisons between patient subgroups or
      individual patient and relevant control population were performed using Two
      Sample T-test. In the group analysis, the hypo-metabolic regions of AD patients
      obtained from different PET centers were similar and consistent. The common hypo
      metabolic cerebral areas were located bilaterally in the posterior cingulate and
      medial parietal cortex, temporo-parietal cortex, prefrontal cortex, and the
      middle and inferior temporal gyrus (uncorrected, p<0.001). In the analysis of
      each individual subject, the location of declined posterior cingulate and medial
      parietal cortex, temporo-parietal cortex and temporal lobe were found highly
      consistent with relevant characteristic regions obtained in the group analysis
      and were selected for diagnostic purposes. Complete typical hypo-metabolic
      pattern was observed in 67% and 54% of AD patients in two sets of 3D scans,
      respectively. Only 27% and 33.3% patients showed full typical pattern in two sets
      of 2D scans. The results indicated that FDG PET measures and SPM can 4 provide a
      valuable reference for clinical diagnosis of AD patients. The potential influence
      of acquisition mode on the clinical diagnosis of AD was suggested for further
      evaluation.

PMID- 20157249
TI  - The CST3 BB genotype and low cystatin C cerebrospinal fluid levels are associated
      with dementia in Lewy body disease.
AB  - A large proportion of demented Lewy body disease patients have Alzheimer's
      disease (AD)- like pathology, in particular amyloid-beta (Abeta) plaques.
      Cystatin C (CysC) is a carrier of soluble Abeta (42) in the cerebrospinal fluid
      (CSF) and reduces Abeta plaque formation. The CST3 BB genotype leads to a reduced
      secretion of the protein in vitro and increases the risk for AD, suggesting that
      variability in the CST3 gene and CysC protein concentration may be associated
      with dementia in Lewy body disease. We therefore determined the CST3 genotype in
      51 demented and 71 nondemented Lewy body disease patients, and in 52 controls, as
      well as CSF CysC and Abeta (42) levels from 132 of these subjects. The CST3 BB
      genotype was associated with lowered CSF CysC levels and with dementia. Demented
      Lewy body disease patients had decreased CSF CysC levels. The correlation between
      CSF CysC and Abeta (42) levels was high in non-demented subjects, but poor in
      demented patients. We conclude that, in Lewy body disease, the CST3 BB genotype
      and low CSF CysC levels are associated with dementia, possibly through a
      disturbed elimination of soluble Abeta(42).

PMID- 20157250
TI  - Higher luteinizing hormone is associated with poor memory recall: the health in
      men study.
AB  - Elevated levels of gonadotropins have been observed in patients with Alzheimer's
      disease and have been associated with poorer cognition in women, but not men. The
      aim of this study was to explore the relationship between gonadotropins and
      cognition in a cohort of 585 healthy, community-dwelling men aged 70-87 years.
      Cognitive function was assessed with the California Verbal Learning Test Second
      Edition (CVLT-II) and the Standardized Mini-Mental State Examination (SMMSE).
      Testosterone, sex hormone binding globulin, and luteinizing hormone levels were
      assayed from early morning sera. Free testosterone was calculated using mass
      action equations. In linear regression analyses, neither total nor free
      testosterone levels were associated with measures of immediate or delayed recall.
      Higher levels of luteinizing hormone were associated with poorer performance on a
      measure of immediate recall (CVLT-II trials 1-5 total score) independent of total
      and free testosterone levels. The association remained after adjustment for age,
      educational attainment, and depression. In contrast, only total and free
      testosterone levels were associated with SMMSE score. These findings suggest a
      role for both androgens and gonadotropins in differing cognitive domains, and
      that gonadotropins may influence cognition independent of sex steroids.

PMID- 20157251
TI  - Tau dephosphorylation potentiates apoptosis by mechanisms involving a failed
      dephosphorylation/activation of Bcl-2.
AB  - Phosphorylation of tau, a major microtubule-associated protein, has been recently
      discovered to affect cell apoptosis. While the phosphorylation of tau is
      dynamically regulated, the role of tau dephosphorylation in cell viability is
      elusive. Here, we observed that the cells bearing high level of the
      dephosphorylated tau at Tau-1 epitope were more vulnerable to the apoptosis
      induced by staurosporine, camptothecin, and hydrogen peroxide, though the general
      outcome of tau expression was still anti-apoptotic. Further studies demonstrate
      that co-expression of tau and protein phosphatase 2A catalytic subunit (PP2Ac),
      the most active tau phosphatase, potentiates cell apoptosis with a correlatively
      increased dephosphorylation of tau and phosphorylation of Bcl-2 at Ser87 (pS87
      Bcl2, the inactive form of the anti-apoptotic factor), whereas expression of
      PP2Ac alone in the absence of tau decreases the levels of pS87-Bcl2 and cleaved
      PARP, markers of early apoptosis. Finally, both tau and Bcl-2 were co
      immunoprecipitated with PP2Ac, but the binding level of Bcl-2 with PP2Ac
      decreased prominently when tau was co-expressed. These data suggest that tau
      dephosphorylation by PP2Ac facilitates cell apoptosis with the mechanisms
      involving a failed dephosphorylation/activation of Bcl-2.

PMID- 20157253
TI  - Ginsenoside Rg1 attenuates amyloid-beta content, regulates PKA/CREB activity, and
      improves cognitive performance in SAMP8 mice.
AB  - It is well established that the presence of soluble amyloid-beta protein (Abeta)
      correlates with the severity of dementia in Alzheimer's disease (AD). Several
      lines of evidence indicate that cyclic AMP responsive element binding protein
      (CREB) and protein kinase A (PKA) are involved in soluble Abeta-trigged
      disruption of synaptic plasticity in early AD. Previously we demonstrated the
      beneficial effects of ginsenoside Rg1 on Abeta-induced neuronal insult.
      Therefore, in the present study, we examined the effects of long-term consumption
      of Rg1 on the cerebral Abeta content and PKA/CREB signaling molecules, as well as
      cognitive performance in senescence-accelerated mouse prone 8 (SAMP8). Notably, a
      significant dose-dependent reduction of soluble Abeta(1-40) was shown in the
      hippocampus of SAMP8 mice after administration with ginsenoside Rg1 for 3 months.
      Furthermore, Rg1 treatment resulted in a significant decrease of hippocampal PKA
      RIIalpha level (isoform IIalpha of the regulatory subunit of PKA). In contrast,
      phospho-CREB and brain derived neurotrophic factor (BDNF) levels were
      dramatically increased in the hippocampus of SAMP8 treated with Rg1.
      Additionally, administration of ginsenoside Rg1 consequently improved learning
      and memory outcomes in SAMP8 mice. These data suggest that long-term consumption
      of ginsenoside Rg1 may delay cognitive decline, associated with significant
      effects on Abeta generation, PKA/CREB activity, as well as BDNF content in the
      brain. These data provide further support for the therapeutic or intervention
      potency of ginsenoside Rg1 in the early stage of AD.

PMID- 20157252
TI  - Microstructural diffusion changes are independent of macrostructural volume loss
      in moderate to severe Alzheimer's disease.
AB  - Although it is established that Alzheimer's disease (AD) leads to cerebral
      macrostructural atrophy, microstructural diffusion changes have also been
      observed, but it is not yet known whether these changes offer unique information
      about the disease pathology. Thus, a multi-modal imaging study was conducted to
      determine the independent contribution of each modality in moderate to severe AD.
      Seventeen patients with moderate-severe AD and 13 healthy volunteers underwent
      diffusion-weighted and T1-weighted MR scanning. Images were processed to obtain
      measures of macrostructural atrophy (gray and white matter volumes) and
      microstructural damage (fractional anisotropy and mean diffusivity).
      Microstructural diffusion changes independent of macrostructural loss were
      investigated using an ANCOVA where macrostructural maps were used as voxel-wise
      covariates. The reverse ANCOVA model was also assessed, where macrostructural
      loss was the dependent variable and microstructural diffusion tensor imaging maps
      were the imaging covariates. Diffusion differences between patients and controls
      were observed after controlling for volumetric differences in medial temporal,
      retrosplenial regions, anterior commissure, corona radiata, internal capsule,
      thalamus, corticopontine tracts, cerebral peduncle, striatum, and precentral
      gyrus. Independent volumetric differences were observed in the entorhinal cortex,
      inferior temporal lobe, posterior cingulate cortex, splenium and cerebellum.
      While it is well known that AD is associated with pronounced volumetric change,
      this study suggests that measures of microstructure provide unique information
      not obtainable with volumetric mapping in regions known to be pivotal in AD and
      in those thought to be spared. As such this work provides great understanding of
      the topography of pathological changes in AD that can be captured with imaging.

PMID- 20157254
TI  - LPYFDa neutralizes amyloid-beta-induced memory impairment and toxicity.
AB  - Misfolding, oligomerization, and aggregation of the amyloid-beta (Abeta) peptide
      is widely recognized as a central event in the pathogenesis of Alzheimer's
      disease (AD). Recent studies have identified soluble Abeta oligomers as the main
      pathogenic agents and provided evidence that such oligomeric Abeta aggregates are
      neurotoxic, disrupt synaptic plasticity, and inhibit long-term potentiation. A
      promising therapeutic strategy in the battle against AD is the application of
      short synthetic peptides which are designed to bind to specific Abeta-regions
      thereby neutralizing or interfering with the devastating properties of oligomeric
      Abeta species. In the present study, we investigated the neuroprotective
      properties of the amyloid sequence derived pentapeptide LPYFDa in vitro as well
      as its memory preserving capacity against Abeta(42)-induced learning deficits in
      vivo. In vitro we showed that neurons in culture treated with LPYFDa are
      protected against Abeta (42) -induced cell death. Moreover, in vivo LPYFDa
      prevented memory impairment tested in a contextual fear conditioning paradigm in
      mice after bilateral intrahippocampal Abeta (42) injections. We thus showed for
      the first time that an anti-amyloid peptide like LPYFDa can preserve memory by
      reverting Abeta (42) oligomer-induced learning deficits.

PMID- 20157255
TI  - Leptin reduces the accumulation of Abeta and phosphorylated tau induced by 27
      hydroxycholesterol in rabbit organotypic slices.
AB  - Accumulation of amyloid-beta (Abeta) peptide and deposition of
      hyperphosphorylated tau protein are two major pathological hallmarks of
      Alzheimer's disease (AD). We have shown that cholesterol-enriched diets and its
      metabolite 27-hydroxycholesterol (27-OHC) increase Abeta and phosphorylated tau
      levels. However, the mechanisms by which cholesterol and 27-OHC regulate Abeta
      production and tau phosphorylation remain unclear. Leptin, an adipocytokine
      involved in cell survival and in learning, has been demonstrated to regulate
      Abeta production and tau hyperphosphorylation in transgenic mice for AD. However,
      the involvement of leptin signaling in cholesterol and cholesterol metabolites
      induced Abeta accumulation and tau hyperphosphorylation are yet to be examined.
      In this study, we determined the effect of high cholesterol diet and 27-OHC on
      leptin expression levels and the extent to which leptin treatment affects 27-OHC
      induced AD-like pathology. Our results show that feeding rabbits a 2% cholesterol
      enriched diet for 12 weeks reduces the levels of leptin by approximately 80% and
      incubating organotypic slices from adult rabbit hippocampus with 27-OHC reduced
      leptin levels by approximately 30%. 27-OHC induces a 1.5-fold increase in Abeta
      (40) and a 3-fold increase in Abeta (42) and in phosphorylated tau. Treatment
      with leptin reversed the 27-OHC-induced increase in Abeta and phosphorylated tau
      by decreasing the levels of BACE-1 and GSK-3beta respectively. Our results
      suggest that cholesterol-enriched diets and cholesterol metabolites induce AD
      like pathology by altering leptin signaling. We propose that leptin
      administration may prevent the progression of sporadic forms of AD that are
      related to increased cholesterol and oxidized cholesterol metabolite levels.

PMID- 20157256
TI  - Progressive age-related impairment of the late long-term potentiation in
      Alzheimer's disease presenilin-1 mutant knock-in mice.
AB  - Presenilin 1 (PS1) mutations are responsible for many early-onset familial
      Alzheimer's disease (FAD) cases. While increasing evidence points to impaired
      synaptic plasticity as an early event in AD, PS1 mutant mice exhibit a
      paradoxical increase in hippocampal long-term potentiation (LTP). Among PS1 mouse
      models, PS1 M146V mutant knock-in mice (PS1KI) are particularly interesting in
      that they exhibit memory impairment in spatial tasks. Here we investigated the
      effects of aging on two forms of LTP in PS1KI mice, the widely-studied early
      phase of LTP (E-LTP) and a particular form of LTP called late-LTP (L-LTP) which
      requires transcription and protein synthesis. L-LTP is thought to be critical for
      long-term memory. We found a lower L-LTP maintenance phase in PS1KI mice compared
      to wild type littermates at 3 months of age. As the mice age, they exhibit
      impairment of both the induction and maintenance phases of LTP. When E-LTP and
      NMDA receptor-mediated transmission were analyzed, PS1KI mice displayed an
      increase at 3 months compared to wild type littermates; this difference did not
      persist at older ages and finally decreased at 12 months. These results reveal an
      L-LTP decrease in PS1 mutant mice at an early stage, which occurs coincidently
      with a paradoxical enhancement of E-LTP. The observation of a decrease in both
      forms of LTP during aging supports the view that PS1KI mice are a valuable model
      for the study of age-dependent synaptic dysfunction and cognitive decline in AD.

PMID- 20157257
TI  - Artificial neural networks identify the predictive values of risk factors on the
      conversion of amnestic mild cognitive impairment.
AB  - The search for markers that are able to predict the conversion of amnestic mild
      cognitive impairment (aMCI) to Alzheimer's disease (AD) is crucial for early
      mechanistic therapies. Using artificial neural networks (ANNs), 22 variables that
      are known risk factors of AD were analyzed in 80 patients with aMCI, for a period
      spanning at least 2 years. The cases were chosen from 195 aMCI subjects recruited
      by four Italian Alzheimer's disease units. The parameters of glucose metabolism
      disorder, female gender, and apolipoprotein E epsilon3/epsilon4 genotype were
      found to be the biological variables with high relevance for predicting the
      conversion of aMCI. The scores of attention and short term memory tests also were
      predictors. Surprisingly, the plasma concentration of amyloid-beta (42) had a low
      predictive value. The results support the utility of ANN analysis as a new tool
      in the interpretation of data from heterogeneous and distinct sources.

PMID- 20157258
TI  - Specific neuromodulatory actions of amyloid-beta on dopamine release in rat
      nucleus accumbens and caudate putamen.
AB  - We previously demonstrated that amyloid-beta (Abeta) has a neuromodulatory action
      in the nucleus accumbens (NAc). In this area of the brain, the peptide disrupts
      the cholinergic control of dopamine (DA) release both in vivo and in vitro. The
      aim of the present work was to extend the research on the neuromodulatory effect
      of Abeta (1-40) on DA transmission to different release stimuli and to another
      dopaminergic brain area, the caudate putamen (CPu), in order to clarify whether
      the effect of the peptide is stimulus- or brain area-selective. We performed both
      in vivo (microdialysis associated to HPLC) and in vitro studies (synaptosomes in
      superfusion). Both in NAc and in CPu and both in vivo and in vitro, Abeta did not
      affect either basal or potassium-stimulated DA release. In CPu, the Abeta ability
      to impair the DA release evoked by the cholinergic agonist carbachol, observed in
      NAc, was confirmed only in vitro. Moreover, in vitro Abeta affected a specific
      component of the DA overflow evoked by the non-selective metabotropic glutamate
      receptors agonist t-ACPD. Altogether, these results show that Abeta may have
      different neuromodulatory actions depending upon the secretory stimulus and, in
      vivo, the brain area investigated.

PMID- 20157259
TI  - Fibrillar Abeta (1-42) enhances NMDA receptor sensitivity via the integrin
      signaling pathway.
AB  - The aggregated form of amyloid-beta (Abeta) (1-42) has been shown to increase N
      methyl-D-aspartic acid (NMDA) evoked neuronal activity in vivo. Here we further
      characterized this phenomenon by investigating the role of integrin activation
      and downstream Src kinase activity using in vivo electrophysiology and in vitro
      intracellular Ca (2+) measurements. Pretreatment of differentiated SH-SY5Y cells
      with fibrillar Abeta (1-42) markedly enhanced the intracellular calcium increases
      caused by NMDA receptor (NMDA-R) stimulation. Function blocking antibody against
      beta1 integrin depressed the facilitatory effects of Abeta (1-42). Similarly,
      Abeta (1-42) facilitated NMDA-R driven firing of hippocampal neurons in vivo, and
      this effect was reduced by neutralizing antibody against beta1 integrins. The
      positive action of Abeta (1-42) on NMDA-R dependent responses was also depressed
      by an inhibitor known to block Src kinase. These results support the hypothesis
      that aggregated Abeta (1-42) is recognized by the beta1 subunit containing
      integrins and may induce a Src kinase dependent NMDA receptor phosphorylation.

PMID- 20157260
TI  - Effects of increased iron intake during the neonatal period on the brain of adult
      AbetaPP/PS1 transgenic mice.
AB  - The present study was aimed to investigate neuropathological changes in
      AbetaPP/PS1 transgenic mice (Tg), as a model of Alzheimer's disease, subjected to
      supplementary iron administration in a critical postnatal period, in order to
      reveal the interaction of genetic and environmental risk factors in the
      pathogenesis of the disease. Twelve Tg and 10 wild-type (Wt) littermates were
      administered iron between the 12th and 14th post-natal days (TgFe, WtFe); 11 Tg
      and 15 Wt received vehicle (sorbitol 5%) alone in the same period (TgSb, WtSb).
      Mice were killed at the age of six months and processed for morphological and
      biochemical studies. No modifications in amyloid-beta burden were seen in iron
      treated and non-iron-treated AbetaPP/PS1 mice. No differences in microglial
      reactions were observed when comparing the four groups of mice. Yet increased
      astrocytosis, as revealed by densitometry of GFAP-immunoreactive astrocytes, and
      increased expression levels of GFAP, as revealed by gel electrophoresis and
      western blotting, were found in iron-treated mice (both Tg and Wt) when compared
      with TgSb and WtSb. This was accompanied by significant changes in brain fatty
      acid composition in AbetaPP/PS1 mice that led to a lower membrane
      peroxidizability index and to reduced protein oxidative damage, as revealed by
      reduced percentages of the oxidative stress markers: glutamic semialdehyde,
      aminoadipic semialdehyde, Nepsilon-carboxymethyl-lysine, Nepsilon-carboxyethyl
      lysine, and Nepsilon-malondialdehyde-lysine. These findings demonstrate that
      transient dietary iron supplementation during the neonatal period is associated
      with cellular and metabolic imprinting in the brain in adult life, but it does
      not interfere with the appearance of amyloid plaques in AbetaPP/PS1 transgenic
      mice.

PMID- 20157262
TI  - The Society for Neuroscience 2009 Meeting Report, Part 1.

PMID- 20157264
TI  - Synchrotron radiation in soil and geosciences.

PMID- 20157261
TI  - The heme degradation pathway is a promising serum biomarker source for the early
      detection of Alzheimer's disease.
AB  - One of the remaining challenges in Alzheimer's disease (AD) research is the
      establishment of biomarkers for early disease detection. As part of a prospective
      study spanning a period of five years, we have collected serial serum samples
      from cognitively normal, mild cognitively impaired (MCI), and mild AD
      participants, including same patient samples before and after cognitive decline.
      Using mass spectrometry we identified several promising leads for biomarker
      development, such as prosaposin, phospholipase D1, biliverdin reductase B, and
      S100 calcium binding protein A7. Selected candidate markers were verified using
      reverse phase protein microarray assays. Of 15 protein/protein abundance ratios
      that were significantly altered in sera from subjects with mild AD compared to
      Normal or MCI subjects, 14 were composed of ratios containing heme oxygenase-1,
      biliverdin reductase A, or biliverdin reductase B. Moreover, an increase in the
      protein abundance ratio of matrix metallopeptidase 9/biliverdin reductase
      differentiated stable MCI subjects from MCI subjects progressing into mild AD
      before the onset of cognitive decline. These findings strongly implicate the heme
      degradation pathway as a promising source of protein biomarkers for the early
      detection of AD.

PMID- 20157265
TI  - X-ray spectromicroscopy in soil and environmental sciences.
AB  - X-ray microscopy is capable of imaging particles in the nanometer size range
      directly with sub-micrometer spatial resolution and can be combined with high
      spectral resolution for spectromicroscopy studies. Two types of microscopes are
      common in X-ray microscopy: the transmission X-ray microscope and the scanning
      transmission X-ray microscope; their set-ups are explained in this paper. While
      the former takes high-resolution images from an object with exposure times of
      seconds or faster, the latter is very well suited as an analytical instrument for
      spectromicroscopy. The morphology of clusters or particles from soil and sediment
      samples has been visualized using a transmission X-ray microscope. Images are
      shown from a cryo-tomography experiment based on X-ray microscopy images to
      obtain information about the three-dimensional structure of clusters of humic
      substances. The analysis of a stack of images taken with a scanning transmission
      X-ray microscope to combine morphology and chemistry within a soil sample is
      shown. X-ray fluorescence is a method ideally applicable to the study of
      elemental distributions and binding states of elements even on a trace level
      using X-ray energies above 1 keV.

PMID- 20157267
TI  - Assessment of sulfur and iron speciation in a soil aggregate by combined S and Fe
      micro-XANES: microspatial patterns and relationships.
AB  - To test whether synchrotron-based spectromicroscopy can be used to identify
      spatial patterns of sulfur (S) and iron (Fe) speciation as well as relationships
      between the speciation of S and Fe in soil colloids or aggregates at the
      micrometre and sub-micrometre level, an anoxically prepared dissected soil
      aggregate (size approximately 1 mm(3)) was analyzed by micro-XANES at the K-edges
      of S (2472 eV) and Fe (7112 eV). The experiment included (i) elemental mapping at
      the S K-edge (S, Si, Al) and the Fe K-edge (Fe, Si), (ii) acquisition of 300
      microm x 300 microm images of the region of interest with X-ray energies of 2474
      eV (addressing reduced organic and inorganic S), 2483 eV (total S), 7121 eV
      (divalent Fe) and 7200 eV (total Fe), as well as (iii) acquisition of S and Fe
      micro-XANES spectra at two different positions, where image analysis suggested
      the dominance of reduced and oxidized S and Fe, respectively. Image analysis
      revealed a heterogeneous distribution of total Si, S and Fe as well as of
      different S and Fe species in the aggregate. Microregions which were either
      enriched in reduced or in oxidized S and Fe could be identified. A microregion
      with a large contribution of oxidized S (sulfate, sulfonate) to total S contained
      exclusively Fe(III) oxyhydroxides (probably ferrihydrite) as S-bearing phase,
      whereas another microregion with a large contribution of reduced organic S
      (thiol, organic disulfide) to total S contained a small amount of Fe(II)-bearing
      silicate in addition to the dominating Fe(III) oxyhydroxides. Our results show
      that combined S and Fe micro-XANES is a powerful tool for studying microscale
      spatial patterns of S and Fe speciation as well as microscale relationships
      between the speciation of S and Fe in soil aggregates.

PMID- 20157266
TI  - Humic acid metal cation interaction studied by spectromicroscopy techniques in
      combination with quantum chemical calculations.
AB  - Humic acids (HA) have a high binding capacity towards traces of toxic metal
      cations, thus affecting their transport in aquatic systems. Eu(III)-HA aggregates
      are studied by synchrotron-based scanning transmission X-ray microscopy (STXM) at
      the carbon K-edge and laser scanning luminescence microscopy (LSLM) at the
      (5)D(0) --> (7)F(1,2) fluorescence emission lines. Both methods provide the
      necessary spatial resolution in the sub-micrometre range to resolve
      characteristic aggregate morphologies: optically dense zones embedded in a matrix
      of less dense material in STXM images correspond to areas with increased Eu(III)
      luminescence yield in the LSLM micrographs. In the C 1s-NEXAFS of metal-loaded
      polyacrylic acid (PAA), used as a HA model compound, a distinct complexation
      effect is identified. This effect is similar to trends observed in the dense
      fraction of HA/metal cation aggregates. The strongest complexation effect is
      observed for the Zr(IV)-HA/PAA system. This effect is confirmed by quantum
      chemical calculations performed at the ab initio level for model complexes with
      different metal centres and complex geometries. Without the high spatial
      resolution of STXM and LSLM and without the combination of molecular modelling
      with experimental results, the different zones indicating a ;pseudo'-phase
      separation into strong complexing domains and weaker complexing domains of HA
      would never have been identified. This type of strategy can be used to study
      metal interaction with other organic material.

PMID- 20157268
TI  - Chromium speciation in mildly heated Cr(VI)-doped latosol soil.
AB  - Cr(VI) chemical reduction in natural organic matter (NOM)-bearing latosol soil
      was investigated under various heating conditions at < or = 378 K. An enhanced
      Cr(VI) reduction rate has been observed for the reaction at 353-378 K. The effect
      of Fe(II) naturally occurring in the latosol soil on Cr(VI) chemical reduction is
      negligible compared with the effect of NOM. Cr(OH)(3) was quantitatively
      specified by X-ray absorption spectroscopy to be the key chromium species (
      approximately 80%) after approximately 90% of Cr(VI) was chemically reduced by
      NOM at 353-378 K. This study indicates a potential strategy for using the heat
      extracted from industrial flue gas with a heat exchanger to chemically reduce
      Cr(VI) in NOM-bearing or organics-amended soils that contain Cr(VI).

PMID- 20157269
TI  - XANES speciation of mercury in three mining districts - Almaden, Asturias
      (Spain), Idria (Slovenia).
AB  - The mobility, bioavailability and toxicity of mercury in the environment strongly
      depend on the chemical species in which it is present in soil, sediments, water
      or air. In mining districts, differences in mobility and bioavailability of
      mercury mainly arise from the different type of mineralization and ore
      processing. In this work, synchrotron-based X-ray absorption near-edge
      spectroscopy (XANES) has been taken advantage of to study the speciation of
      mercury in geological samples from three of the largest European mercury mining
      districts: Almaden (Spain), Idria (Slovenia) and Asturias (Spain). XANES has been
      complemented with a single extraction protocol for the determination of Hg
      mobility. Ore, calcines, dump material, soil, sediment and suspended particles
      from the three sites have been considered in the study. In the three sites,
      rather insoluble sulfide compounds (cinnabar and metacinnabar) were found to
      predominate. Minor amounts of more soluble mercury compounds (chlorides and
      sulfates) were also identified in some samples. Single extraction procedures have
      put forward a strong dependence of the mobility with the concentration of
      chlorides and sulfates. Differences in efficiency of roasting furnaces from the
      three sites have been found.

PMID- 20157271
TI  - Manganese speciation in Diplodon chilensis patagonicus shells: a XANES study.
AB  - X-ray absorption near-edge spectroscopy (XANES) at the Mn K-edge was used to
      investigate the environment of Mn in situ within the growth increments of the
      long-lived freshwater bivalve species Diplodon chilensis patagonicus. Single
      XANES spectra and Mn Kalpha fluorescence distributions were acquired at
      submillimetre resolution (up to 100 microm x 50 microm), at Mn concentrations
      below the weight percent range (100-1000 microg g(-1)) in a high Ca matrix. The
      position and intensity of the pre-edge feature in the shell spectrum resembles
      best that of the Mn(II)-bearing reference compounds, suggesting that this is the
      oxidation state of Mn in the bivalve shells. By comparison with the XANES spectra
      of selected standard compounds, hypotheses about Mn speciation in the shell are
      also reported. In particular, different factors, such as provenance, ontogenetic
      age, variable Mn-concentrations or seasonal shell deposition seem not to
      influence the speciation of the metal in this bivalve species.

PMID- 20157270
TI  - Mercury speciation in the colloidal fraction of a soil polluted by a chlor-alkali
      plant: a case study in the South of Italy.
AB  - Mercury (Hg) speciation in different size fractions of a soil sample collected
      near an industrial area located in the South of Italy, which had been polluted by
      the dumping of Hg-containing wastes from a chlor-alkali plant, was investigated
      by XANES spectroscopy. In particular, a special procedure has been developed to
      study the soil colloidal fraction, both for sample preparation and for XANES data
      collection. In this soil, Hg was speciated in quite insoluble inorganic forms
      such as cinnabar (alpha-HgS), metacinnabar (beta-HgS), corderoite
      (Hg(3)S(2)Cl(2)), and some amorphous Hg, S and Cl-containing species, all derived
      from the land-disposal of K106 Hg-containing wastes. The contribution of the
      above-mentioned chemical forms to Hg speciation changed as a function of particle
      size. For the fraction <2 mm the speciation was: amorphous Hg-S-Cl (34%) >
      corderoite (26%) > cinnabar (20%) = metacinnabar (20%); for the fraction <2
      microm: amorphous Hg-S-Cl (40%) > metacinnabar (24%) > corderoite (20%) >
      cinnabar (16%); and for the fraction 430-650 nm, where most of the colloidal Hg
      was concentrated: amorphous Hg-S-Cl (56%) > metacinnabar (33%) > corderoite (6%)
      > cinnabar (5%). From these data it emerged that, even if Hg was speciated in
      quite insoluble forms, the colloidal fraction, which is the most mobile and thus
      the most dangerous, was enriched in relatively more soluble species (i.e.
      amorphous Hg-S-Cl and metacinnabar), as compared with cinnabar. This aspect
      should be seriously taken into account when planning environmental risk
      assessment, since the small particle size in which Hg is concentrated and the
      changing speciation passing from millimetre to nanometre size could turn
      apparently safe conditions into more hazardous ones.

PMID- 20157272
TI  - In situ X-ray absorption spectroscopic studies of copper in a copper-rich sludge
      during electrokinetic treatments.
AB  - Speciation of copper in a copper-rich chemical-mechanical polishing sludge during
      electrokinetic treatment has been studied by in situ extended X-ray absorption
      fine structure (EXAFS) and X-ray absorption near-edge structure (XANES)
      spectroscopy. The least-squares-fitted XANES spectra indicate that the main
      copper species in the sludge are Cu(OH)(2) (74%), nanosize CuO (20-60 nm) (13%)
      and CuO (>100 nm) (13%). The average bond distance and coordination number (CN)
      of Cu-O are 1.96 A and 3.5, respectively. Under electrokinetic treatment (5 V cm(
      1)) for 120 min, about 85% of the copper is dissolved in the electrolyte, 13% of
      which is migrated and enriched on the cathode. Notably the copper nanoparticles
      in the sludge can also migrate to the cathode under the electric field. By in
      situ EXAFS, it is found that during the electrokinetic treatment the bond
      distance and CN of Cu-O are increased by 0.1 A and 0.9, respectively.

PMID- 20157273
TI  - Synchrotron-based X-ray diffraction of the lead apatite series
      Pb(10)(PO(4))(6)Cl(2)-Pb(10)(AsO(4))(6)Cl(2).
AB  - A number of compounds of the pyromorphite-mimetite solid solution series were
      synthesized at room temperature and analyzed with infrared spectroscopy and
      powder X-ray diffraction. High-resolution high-quality powder diffraction data
      were obtained by means of the state-of-the-art instrument at the 11-BM beamline
      of the Advanced Photon Source at Argonne National Laboratory, Argonne, IL, USA.
      The unit-cell dimensions, atomic position and atomic displacement parameters, as
      well as site occupancy for analyzed phases, were refined by the Rietveld method
      and reported herein for the first time. The results of this study indicate that
      the pyromorphite-mimetite series is continuous in near-Earth-surface
      environments. Detailed structural changes caused by P(5+)-As(5+) substitutions in
      minerals from the pyromorphite-mimetite solid solution series are reported.

PMID- 20157274
TI  - The contribution of synchrotron X-ray computed microtomography to understanding
      volcanic processes.
AB  - A series of computed microtomography experiments are reported which were
      performed by using a third-generation synchrotron radiation source on volcanic
      rocks from various active hazardous volcanoes in Italy and other volcanic areas
      in the world. The applied technique allowed the internal structure of the
      investigated material to be accurately imaged at the micrometre scale and three
      dimensional views of the investigated samples to be produced as well as three
      dimensional quantitative measurements of textural features. The geometry of the
      vesicle (gas-filled void) network in volcanic products of both basaltic and
      trachytic compositions were particularly focused on, as vesicle textures are
      directly linked to the dynamics of volcano degassing. This investigation provided
      novel insights into modes of gas exsolution, transport and loss in magmas that
      were not recognized in previous studies using solely conventional two-dimensional
      imaging techniques. The results of this study are important to understanding the
      behaviour of volcanoes and can be combined with other geosciences disciplines to
      forecast their future activity.

PMID- 20157275
TI  - Synchrotron radiation computed laminography for polymer composite failure
      studies.
AB  - Synchrotron radiation computed laminography is applied to the three-dimensional
      micro-imaging of damage in large polymer composite plates with high spatial
      resolution. The influence of different experimental conditions is studied with
      respect to measurement time optimization, dose minimization and reduction of
      artefacts in the reconstructed images. Failures like delaminations, transverse
      ply cracks and splits are observed under in situ loads. The propagation of up to
      2 mm-long cracks is non-destructively followed in situ and investigated in
      detail. By phase retrieval using a single detector distance, the failures can be
      easily visualized in three dimensions.

PMID- 20157276
TI  - Microcrystallography using single-bounce monocapillary optics.
AB  - X-ray microbeams have become increasingly valuable in protein crystallography. A
      number of synchrotron beamlines worldwide have adapted to handling smaller and
      more challenging samples by providing a combination of high-precision sample
      positioning hardware, special visible-light optics for sample visualization, and
      small-diameter X-ray beams with low background scatter. Most commonly, X-ray
      microbeams with diameters ranging from 50 microm to 1 microm are produced by
      Kirkpatrick and Baez mirrors in combination with defining apertures and scatter
      guards. A simple alternative based on single-bounce glass monocapillary X-ray
      optics is presented. The basic capillary design considerations are discussed and
      a practical and robust implementation that capitalizes on existing beamline
      hardware is presented. A design for mounting the capillary is presented which
      eliminates parasitic scattering and reduces deformations of the optic to a degree
      suitable for use on next-generation X-ray sources. Comparison of diffraction data
      statistics for microcrystals using microbeam and conventional aperture-collimated
      beam shows that capillary-focused beam can deliver significant improvement.
      Statistics also confirm that the annular beam profile produced by the capillary
      optic does not impact data quality in an observable way. Examples are given of
      new structures recently solved using this technology. Single-bounce monocapillary
      optics can offer an attractive alternative for retrofitting existing beamlines
      for microcrystallography.

PMID- 20157277
TI  - Application of kinoform lens for X-ray reflectivity analysis.
AB  - In this paper the first practical application of kinoform lenses for the X-ray
      reflectivity characterization of thin layered materials is demonstrated. The
      focused X-ray beam generated from a kinoform lens, a line of nominal size
      approximately 50 microm x 2 microm, provides a unique possibility to measure the
      X-ray reflectivities of thin layered materials in sample scanning mode. Moreover,
      the small footprint of the X-ray beam, generated on the sample surface at grazing
      incidence angles, enables one to measure the absolute X-ray reflectivities. This
      approach has been tested by analyzing a few thin multilayer structures. The
      advantages achieved over the conventional X-ray reflectivity technique are
      discussed and demonstrated by measurements.

PMID- 20157278
TI  - Development of a differential pumping system for soft X-ray beamlines for
      windowless experiments under normal atmospheric conditions.
AB  - A novel design for a differential pumping system has been investigated. This
      system allows windowless experiments in a soft X-ray beamline under normal
      atmospheric conditions. The new design consists of an aperture-based four-stage
      differential pumping system, based on a simple model calculation. A prototype
      system with a total length of 600 mm was constructed to confirm the validity of
      the design concept. Relatively short conductance-limiting components allow easy
      installation and alignment of the system on a synchrotron beamline. The
      fabricated system was installed on a beamline to test the transmission of soft X
      rays through atmospheric helium.

PMID- 20157279
TI  - X-ray microdiffraction analysis of radiation-induced defects in single grains of
      polycrystalline Fe.
AB  - Single-crystal diffuse X-ray scattering was used to characterize radiation
      induced defects in individual grains of a polycrystalline proton-irradiated Fe
      foil. The grains were probed with an intense 1 microm X-ray beam to demonstrate
      that both polycrystalline and micrometer-scale samples can be studied with single
      crystal-like signal-to-noise. Scattering was measured with an X-ray-sensitive
      area detector, which measures intensity over a surface in reciprocal space. By
      scanning the X-ray energy, the intensity was measured over reciprocal-space
      volumes. Since the sample is not rotated, the real-space scattering volume does
      not change. Methods to minimize experimental artifacts arising from the use of an
      area detector are described.

PMID- 20157280
TI  - One-dimensional small-angle X-ray scattering tomography of dip-coated polyamide 6
      monofilaments.
AB  - A synchrotron study is presented in which the concept of one-dimensional
      tomographic reconstruction of small-angle X-ray scattering patterns is applied to
      investigate polyamide 6 monofilaments, dip-coated with alumina particles. The
      filaments are scanned with a focused synchrotron beam and the resulting
      scattering patterns are recorded with a PILATUS 2M detector. The reconstructed
      sequence of SAXS images reflects the local nanostructure variation along the
      filament radius. In particular, the influence of coating process parameters on
      the polyamide 6 is investigated.

PMID- 20157281
TI  - Synchrotron radiation analysis of possible correlations between metal status in
      human cementum and periodontal disease.
AB  - Periodontitis is a serious disease that affects up to 50% of an adult population.
      It is a chronic condition involving inflammation of the periodontal ligament and
      associated tissues leading to eventual tooth loss. Some evidence suggests that
      trace metals, especially zinc and copper, may be involved in the onset and
      severity of periodontitis. Thus we have used synchrotron X-ray fluorescence
      imaging on cross sections of diseased and healthy teeth using a microbeam to
      explore the distribution of trace metals in cementum and adhering plaque. The
      comparison between diseased and healthy teeth indicates that there are elevated
      levels of zinc, copper and nickel in diseased teeth as opposed to healthy teeth.
      This preliminary correlation between elevated levels of trace metals in the
      cementum and plaque of diseased teeth suggests that metals may play a role in the
      progress of periodontitis.

PMID- 20157282
TI  - Trace element analysis of hairs in patients with dementia.
AB  - The trace elements of scalp hair samples from > or =60-year-old dementia patients
      and normal persons have been studied by X-ray absorption near-edge spectroscopy
      (XANES) in fluorescent mode and wavelength-dispersive X-ray fluorescence
      spectrometry. Comparisons of hair trace element levels of age-matched dementia
      patients and normal persons revealed significantly elevated amounts of calcium,
      chlorine and phosphorus in dementia patients relative to normal persons. The
      results of XANES measurements identify the chemical forms of deposited calcium
      and phosphorus in the hair samples of both dementia patients and normal persons
      to be calcium chloride (CaCl(2)) and phosphate (PO(4)(3-)), respectively. The
      amount of sulfur in hairs of dementia patients was found to be not significantly
      different from that in normal persons. The sulfur K-edge XANES spectra, however,
      show significantly higher accumulations of sulfur in the sulfate (SO(4)(2-)) form
      in hairs of Alzheimer's disease and Parkinson's disease dementia patients. This
      study presents the possible roles of calcium, chlorine, phosphorus and sulfur in
      the etiology of dementia in elderly patients.

PMID- 20157283
TI  - Spectroscopic set-up for simultaneous UV-Vis/(Q)EXAFS in situ and in operando
      studies of homogeneous reactions under laboratory conditions.
AB  - A novel experimental set-up for in operando studies of homogeneous catalyzed
      reactions under laboratory conditions has been developed and tested. It combines
      time-resolved X-ray absorption spectroscopy with UV/Vis spectroscopy. The
      reaction solution is stirred in a vessel and pumped in a circle by a peristaltic
      free gear-wheel through a measurement cell. The X-ray and UV/Vis beams probe the
      same sample volume of the cell orthogonally. Reactants can be added to the
      reaction mixture in the course of the measurements and a defined gas atmosphere
      can be adjusted up to a pressure of 10 bar. The in situ reduction of cerium(IV)
      ammonium nitrate to cerium(III) by isopropanol is studied as a test reaction with
      quick-XANES and UV/Vis measurements with a time resolution of 60 s and 1 s,
      respectively.

PMID- 20157284
TI  - Determining the radial pair distribution function from X-ray absorption spectra
      by use of the Landweber iteration method.
AB  - The Landweber iteration approach is used to construct the radial pair
      distribution function (RPDF) from an X-ray absorption (EXAFS) spectrum. The
      physical motivation for the presented investigation is the possibility to also
      reconstruct asymmetric RPDFs from the EXAFS spectra. From the methodical point of
      view the shell fit analysis in the case of complicated spectra would be much more
      eased if the RPDF for the first shell(s) are computed precisely and
      independently. The RPDF, as a solution of the fundamental EXAFS integral
      equation, is examined for theoretical examples, and a detailed noise analysis is
      performed. As a real example the EXAFS spectrum of curium(III) hydrate is
      evaluated in a stable way without supplementary conditions by the proposed
      iteration, i.e. by a recursive application of the EXAFS kernel.

PMID- 20157285
TI  - In vitro synchrotron-based radiography of micro-gap formation at the implant
      abutment interface of two-piece dental implants.
AB  - Micro-gap formation at the implant-abutment interface of two-piece dental
      implants was investigated in vitro using high-resolution radiography in
      combination with hard X-ray synchrotron radiation. Images were taken with the
      specimen under different mechanical loads of up to 100 N. The aim of this
      investigation was to prove the existence of micro-gaps for implants with conical
      connections as well as to study the mechanical behavior of the mating zone of
      conical implants during loading. Synchrotron-based radiography in comparison with
      classical laboratory radiography yields high spatial resolution in combination
      with high contrast even when exploiting micro-sized features in highly
      attenuating objects. The first illustration of a micro-gap which was previously
      indistinguishable by laboratory methods underlines that the complex micro
      mechanical behavior of implants requires further in vitro investigations where
      synchrotron-based micro-imaging is one of the prerequisites.

PMID- 20157287
TI  - Serum ghrelin and the prediction of the development of impaired glucose
      regulation and Type 2 diabetes in middle-aged subjects.
AB  - BACKGROUND: Ghrelin is a peptide hormone which has been shown to associate with
      obesity, hypertension and Type 2 diabetes (T2DM) in cross-sectional studies. AIM:
      To study whether total ghrelin levels have predictive value for the incidence of
      impaired glucose regulation (IGR) or T2DM. SUBJECTS AND METHODS: The subjects of
      this prospective follow-up study (no.=201) belonged to a population-based cohort
      collected in Northern Finland. Oral glucose tolerance tests (OGTT) and
      measurements of fasting serum total ghrelin, lipids, blood pressure and body mass
      index were performed at the beginning and at the end of the study. The mean
      follow-up time was 5.1 yr. The subjects had normal glucose tolerance (NGT) at the
      beginning of the study. RESULTS: T2DM developed in 6 (3%), impaired fasting
      glucose (IFG) in 6 (3%) and impaired glucose tolerance (IGT) in 35 (17.4%)
      subjects. The baseline ghrelin concentrations did not differ between the two
      studied groups: median fasting serum total ghrelin concentration was 733 pg/ml
      (25th-75th percentiles: 571-961 pg/ml) among those who maintained NGT, and 661
      pg/ml (25th-75th percentiles: 527- 878 pg/ml) among those who developed IGR (IFG
      and/or IGT) or T2DM (p=0.421). The baseline ghrelin concentrations did not
      explain the changes in the 0-h or 2-h blood glucose concentrations in regression
      models. CONCLUSIONS: Our findings suggest that fasting serum total ghrelin levels
      measured at one time point might not have predictive value for the development of
      abnormalities in glucose tolerance.

PMID- 20157288
TI  - Prevalence of growth hormone deficiency in adult polytransfused beta-thalassemia
      patients and correlation with transfusional and chelation parameters.
AB  - BACKGROUND: Dysfunction of GH-IGF-I axis has been described in many patients
      affected by beta-thalassemia major (TM), especially in children and in
      adolescents. Recent studies have demonstrated the necessity to evaluate adult
      patients affected by TM to establish the presence of this alteration which could
      be relevant in the pathogenesis of cardiac and bone disease, frequently present
      in this hematological condition. The pathogenesis of this alteration, correlated
      in the past with iron overload, is not yet completely understood. AIM: The aim of
      this paper is to evaluate GH-IGF-I axis in a group of adult polytransfused beta
      thalassemic patients (TM) and to correlate the results with transfusional and
      chelation parameters. SUBJECTS AND METHODS: We performed an arginine plus GHRH
      stimulation test in 28 adult TM patients. Ferritin, IGF-I, liver enzymes, and
      liver iron concentration, assessed by a superconducting quantum interference
      device (SQUID) susceptometer were also determined. Moreover, in each patient we
      evaluated the bone status by a dual-energy X-ray absorptiometry study. RESULTS:
      We found the presence of GH deficit in 9 patients (32.1%). There were no
      significant differences between the two groups regarding the value of ferritin,
      liver enzymes, and liver iron concentration, assessed by SQUID. The group
      affected by GH deficit showed a worse bone profile. CONCLUSIONS: This study
      confirms the necessity to screen the status of GH/IGF-I axis in this group of
      patients, even in adult age. The presence of GH deficiency does not seem to be
      correlated with the efficacy parameters of transfusional and chelation therapy.
      Other mechanisms, additional to iron overload, could therefore play a role in the
      pathogenesis of this clinical condition. The presence of GH deficit seems to be
      very important on clinical aspects, like bone disease, that are crucial for
      quality of life in these patients.

PMID- 20157289
TI  - Studying synaptic vesicle pools using photoconversion of styryl dyes.
AB  - The fusion of synaptic vesicles with the plasma membrane (exocytosis) is a
      required step in neurotransmitter release and neuronal communication. The
      vesicles are then retrieved from the plasma membrane (endocytosis) and grouped
      together with the general pool of vesicles within the nerve terminal, until they
      undergo a new exo- and endocytosis cycle (vesicle recycling). These processes
      have been studied using a variety of techniques such as electron microscopy,
      electrophysiology recordings, amperometry and capacitance measurements.
      Importantly, during the last two decades a number of fluorescently labeled
      markers emerged, allowing optical techniques to track vesicles in their recycling
      dynamics. One of the most commonly used markers is the styryl or FM dye;
      structurally, all FM dyes contain a hydrophilic head and a lipophilic tail
      connected through an aromatic ring and one or more double bonds (Fig. 1B). A
      classical FM dye experiment to label a pool of vesicles consists in bathing the
      preparation (Fig. 1Ai) with the dye during the stimulation of the nerve
      (electrically or with high K(+)). This induces vesicle recycling and the
      subsequent loading of the dye into recently endocytosed vesicles (Fig. 1A(i
      iii;)). After loading the vesicles with dye, a second round of stimulation in a
      dye-free bath would trigger the FM release through exocytosis (Fig. 1A(iv-v;)),
      process that can be followed by monitoring the fluorescence intensity decrease
      (destaining). Although FM dyes have contributed greatly to the field of vesicle
      recycling, it is not possible to determine the exact localization or morphology
      of individual vesicles by using conventional fluorescence microscopy. For that
      reason, we explain here how FM dyes can also be used as endocytic markers using
      electron microscopy, through photoconversion. The photoconversion technique
      exploits the property of fluorescent dyes to generate reactive oxygen species
      under intense illumination. Fluorescently labeled preparations are submerged in a
      solution containing diaminobenzidine (DAB) and illuminated. Reactive species
      generated by the dye molecules oxidize the DAB, which forms a stable, insoluble
      precipitate that has a dark appearance and can be easily distinguished in
      electron microscopy. As DAB is only oxidized in the immediate vicinity of
      fluorescent molecules (as the reactive oxygen species are short-lived), the
      technique ensures that only fluorescently labeled structures are going to contain
      the electron-dense precipitate. The technique thus allows the study of the exact
      location and morphology of actively recycling organelles.

PMID- 20157290
TI  - Local transplantation of human multipotent adipose-derived stem cells accelerates
      fracture healing via enhanced osteogenesis and angiogenesis.
AB  - Adipose tissue is one of the promising sources of multipotent stem cells in
      human. Human multipotent adipose-derived stem (hMADS) cells have recently been
      isolated and showed differentiation potential into multiple mesenchymal lineages
      in vitro and in vivo. On the basis of these evidences, we examined the
      therapeutic efficacy of hMADS cells for fracture healing in an immunodeficient
      rat femur non-union fracture model. Local transplantation of hMADS cells
      radiographically and histologically promoted fracture healing with significant
      improvement of biomechanical function at the fracture sites compared with local
      transplantation of human fibroblasts (hFB) or PBS administration. Histological
      capillary density and physiological blood flow by laser Doppler perfusion imaging
      were significantly greater in hMADS group than hFB and PBS groups. Expressions of
      intrinsic (rat) bone morphogenetic protein-2 (BMP-2), vascular endothelial growth
      factor (VEGF) and angiopoietin-1 in peri-fracture tissue were upregulated in
      hMADS group than other groups. In addition, presence of BMP-2 or VEGF activated
      the proliferation and migration of hMADS cells in vitro. These results indicate
      that hMADS cells stimulate the interaction between the transplanted cells and the
      resident cells stronger than other cells, and they promote fracture healing more
      effectively. Furthermore, immunohistochemistry for human-specific antibodies
      revealed direct differentiation of hMADS cells into osteoblasts or endothelial
      cells in newly formed callus or vasculature, respectively. RT-PCR for human
      specific primers for osteogenic/endothelial markers also disclosed osteogenic and
      vasculogenic plasticity of the transplanted hMADS cells at the early stage of
      fracture healing. The present results suggest that transplantation of hMADS cells
      may become a useful strategy for cell-based bone regeneration in the future
      clinical setting.

PMID- 20157291
TI  - Hippocampal CA1 atrophy and synaptic loss during experimental autoimmune
      encephalomyelitis, EAE.
AB  - Over half of multiple sclerosis (MS) patients experience cognitive deficits,
      including learning and memory dysfunction, and the mechanisms underlying these
      deficits remain poorly understood. Neuronal injury and synaptic loss have been
      shown to occur within the hippocampus in other neurodegenerative disease models,
      and these pathologies have been correlated with cognitive impairment. Whether
      hippocampal abnormalities occur in MS models is unknown. Using experimental
      autoimmune encephalomyelitis (EAE), we evaluated hippocampal neurodegeneration
      and inflammation during disease. Hippocampal pathology began early in EAE disease
      course, and included decreases in CA1 pyramidal layer volume, loss of inhibitory
      interneurons and increased cell death of neurons and glia. It is interesting to
      note that these effects occurred in the presence of chronic microglial
      activation, with a relative paucity of infiltrating blood-borne immune cells.
      Widespread diffuse demyelination occurred in the hippocampus, but there was no
      significant decrease in axonal density. Furthermore, there was a significant
      reduction in pre-synaptic puncta and synaptic protein expression within the
      hippocampus, as well as impaired performance on a hippocampal-dependent spatial
      learning task. Our results demonstrate that neurodegenerative changes occur in
      the hippocampus during autoimmune-mediated demyelinating disease. This work
      establishes a preclinical model for assessing treatments targeted toward
      preventing hippocampal neuropathology and dysfunction in MS.

PMID- 20157292
TI  - Impairment of ultrastructure and cytoskeleton during progression of cardiac
      hypertrophy to heart failure.
AB  - Studies at the morphological and molecular level have found that transgenic (Tg)
      mice that overexpress myotrophin in the heart develop hypertrophy at the early
      age of 4 weeks; this condition worsens to heart failure (HF) at approximately 36
      weeks. However, how the sustained effects of alteration in cytoarchitecture of
      the contractile machinery lead to malfunction of the normal heart remains
      unclear. Our data have shown that at 4 weeks, the cytoarchitecture observed in
      left ventricular (LV) tissue samples of Tg mice is similar to that of wild-type
      (WT) mice. However, as the disease progresses, cardiomyocytes show deterioration
      in some mitochondrial as well as myofibril features, evidenced by swelling of
      mitochondria, misalignment of myofibril structure, and blurring as well as
      breakage of Z-lines. At 36 weeks of age, Tg mice (the group in transition from
      hypertrophy to HF) show significant degenerative changes in cardiomyocytes,
      including swelling of mitochondria, disruption of the nuclear membrane, and
      absence of myofibril structure. Besides these, formation of myelin bodies was
      also observed, a feature typically found in human hearts with HF. Changes in Z
      line architecture were further confirmed by alteration in the gene expression
      profile of desmin and tubulin, the two main cytoskeletal proteins. We thus
      conclude that Tg mice overexpressing myotrophin show no visible changes in the
      initiation phase (4 weeks); however, as the disease progresses, alterations in
      the cytoskeleton are found during the transition phase from hypertrophy to HF (36
      weeks onward). Our data suggest that treatment for prevention/reversal of
      hypertrophy should start at the early stage of hypertrophy to prevent its
      transition to HF.

PMID- 20157293
TI  - In vivo evidence for the role of RegI in gastric regeneration: transgenic
      overexpression of RegI accelerates the healing of experimental gastric ulcers.
AB  - On the basis of its temporal and spatial pattern of expression during the healing
      of gastric ulcers, RegI is implied to be a key growth factor governing the
      gastric progenitor cell proliferation, which is fundamental for reconstruction of
      the gastric tissue; however, there is no direct in vivo evidence. The aim of this
      study was to use RegI-transgenic (Tg) mice to test the role of RegI protein in
      the healing of experimentally induced gastric ulcers. The stomachs from 48 pairs
      of wild-type (Wt) and Tg littermates were examined for gastric erosions after 24
      h of water-immersion stress, or, 6, 12, 18 and 24 h after oral administration of
      HCl/ethanol. Expression levels of c-fos and c-myc proto-oncogenes were examined
      over time by real-time reverse transcriptase PCR to assess gastric cell
      proliferation. Almost all the littermate pairs tested showed superiority of Tg
      mice over Wt mice in the ability of decreasing ulcer index (UI) (cumulative
      length of erosion). The time-course study revealed that the UIs of Tg were lower
      in the healing phase, and not in the injury phase. The fraction of proliferating
      cells was higher in Tg mice than in Wt mice throughout the time course as
      assessed by c-fos expression levels. This is the first in vivo evidence that RegI
      has a role in gastric ulcer healing. We suggest that RegI exerts its effects by
      promoting growth and not by cytoprotection.

PMID- 20157295
TI  - Educating the public.
AB  - California has one of the most prestigious public university systems. However,
      budget woes and lack of clear strategic planning may undermine its continued
      success.

PMID- 20157294
TI  - Relationship of strain-dependent susceptibility to experimentally induced acute
      pancreatitis with regulation of Prss1 and Spink3 expression.
AB  - To analyze susceptibility to acute pancreatitis, five mouse strains including
      Japanese Fancy Mouse 1 (JF1), C57BL/6J, BALB/c, CBA/J, and C3H/HeJ were treated
      with either a cholecystokinin analog, cerulein, or a choline-deficient, ethionine
      supplemented (CDE) diet. The severity of acute pancreatitis induced by cerulein
      was highest in C3H/HeJ and CBA/J, moderate in BALB/c, and mildest in C57BL/6J and
      JF1. Basal protein expression levels of the serine protease inhibitor, Kazal type
      3 (Spink3) were higher in JF1 and C57BL/6J mice than those of the other three
      strains under normal feeding conditions. After treatment with cerulein,
      expression level of Spink3 increased remarkably in JF1 and mildly in C57BL/6J,
      BALB/c, CBA/J, and C3H/HeJ strains. Increased proteinase, serine, 1 (Prss1)
      protein expression accompanied by increased trypsin activity with cerulein
      treatment was observed in susceptible strains such as CBA/J and C3H/HeJ. Similar
      results were obtained with a CDE diet. In the 3 kb Spink3 promoter region, 92 or
      8 nucleotide changes were found in JF1 or C3H vs C57BL/6J, respectively, whereas
      in the Prss1 promoter region 39 or 46 nucleotide changes were found in JF1 or C3H
      vs C57BL/6J, respectively. These results suggest that regulation of Prss1 and
      Spink3 expression is involved in the susceptibility to experimentally induced
      pancreatitis. The JF1 strain, which is derived from the Japanese wild mouse, will
      be useful to examine new mechanisms that may not be found in other laboratory
      mouse strains.

PMID- 20157296
TI  - In vivo veritas: the surprising roles of Fc receptors in immunity.
AB  - Jeffrey Ravetch describes how he came to identify the in vivo function of the
      once mysterious Fc receptors.

PMID- 20157297
TI  - Vanilloid flavor for a good appetite?

PMID- 20157298
TI  - CD8+ thymocyte differentiation: T cell two-step.

PMID- 20157299
TI  - Voltage control for B cell activation.

PMID- 20157300
TI  - Controlling stem cell fate one substrate at a time.

PMID- 20157302
TI  - Clinical implications of changing definitions within the Gleason grading system.
AB  - Remarkably, more than 40 years after the inception of the Gleason grading system,
      it remains one of the most powerful prognostic predictors in prostate cancer.
      Gleason's original grading system, however, has undergone significant revision
      over the years, first by Gleason and his colleagues, and most recently at the
      2005 International Society of Urological Pathology Consensus Conference. The
      consensus conference and subsequent articles proposing further modifications have
      helped pathologists to adapt the Gleason grading system to current urologic
      practice in a uniform manner. The changing definitions of Gleason pattern 3 and 4
      prostatic adenocarcinoma have tended to narrow the scope of pattern 3 carcinoma
      and widen the scope of pattern 4 carcinoma. These modifications have had an
      important role in improving the inter-observer reproducibility of the Gleason
      system. Whether these changes have a significant impact on the clinical treatment
      of prostate cancer remains to be seen. However, as many of these modifications
      are supported only by a few studies, long-term follow-up studies with clinical
      end points are essential to validate these recommendations.

PMID- 20157303
TI  - Emerging gene and stem cell therapies for the treatment of erectile dysfunction.
AB  - Erectile dysfunction is a prevalent condition that leads to significant morbidity
      and distress, not just for affected men but also for their partners. Very few
      currently available treatments ameliorate the underlying causes of the disorder
      and 'cure' the disease state. Much recent effort has been focused on the
      development of gene and cell-based approaches to rectify the molecular and tissue
      defects responsible for ED. Gene therapy has been investigated in animal models
      as a means to restore normal function to the penis; at this time, however, only
      one human trial has been published in the peer-reviewed literature. Recent gene
      therapy studies have focused on the modulation of enzymes associated with the
      NOS/cGMP pathway, and supplementation of trophic factors, peptides and potassium
      channels. Stem cell therapy has been a topic of interest in more recent years but
      there are currently very few published reports in animal models and none in human
      men. Although stem cell therapy offers the potential for restoration of
      functional tissues, legitimate concerns remain regarding the long-term fate of
      stem cells. The long-term safety of both gene and stem cell therapy must be
      thoroughly investigated before large-scale human studies can be considered.

PMID- 20157304
TI  - Treatment of infertility in men with spinal cord injury.
AB  - Most men with spinal cord injury (SCI) are infertile. Erectile dysfunction,
      ejaculatory dysfunction and semen abnormalities contribute to the problem.
      Treatments for erectile dysfunction include phosphodiesterase type 5 inhibitors,
      intracavernous injections of alprostadil, penile prostheses, and vacuum
      constriction devices. In anejaculatory patients who wish to father children,
      semen retrieval is necessary. Penile vibratory stimulation is recommended as the
      first line of treatment. Patients who fail penile vibratory stimulation can be
      referred for electroejaculation. If this approach is not possible, prostate
      massage is an alternative. Surgical sperm retrieval should be considered as a
      last resort when other methods fail. Most men with SCI have a unique semen
      profile characterized by normal sperm count but abnormally low sperm motility.
      Scientific investigations indicate that accessory gland dysfunction and abnormal
      semen constituents contribute to the problem. Despite abnormalities, sperm from
      men with SCI can successfully induce pregnancy. In selected couples, the simple
      method of intravaginal insemination is a viable option. Another option is
      intrauterine insemination. The efficacy of intrauterine insemination increases as
      the total motile sperm count inseminated increases. In vitro fertilization and
      intracytoplasmic sperm injection are options in cases of extremely low total
      motile sperm count. Reproductive outcomes for SCI male factor infertility are
      similar to outcomes for general male factor infertility.

PMID- 20157305
TI  - The effect of obesity on sperm disorders and male infertility.
AB  - The results of several studies point to an increased likelihood of abnormal semen
      parameters among overweight men, and an elevated risk for subfertility among
      couples in which the male partner is obese. Obesity is, therefore, associated
      with a higher incidence of male factor infertility. Several mechanisms might
      account for the effect of obesity on male infertility, both directly and
      indirectly, by inducing sleep apnea, alterations in hormonal profiles (reduced
      inhibin B and androgen levels accompanied by elevated estrogen levels) and
      increased scrotal temperatures, ultimately manifesting as impaired semen
      parameters (decreased total sperm count, concentration and motility; increased
      DNA fragmentation index). Neither the reversibility of obesity-associated male
      infertility with weight loss nor effective therapeutic interventions have been
      studied in-depth. The increasing prevalence of obesity calls for greater clinical
      awareness of its effects on fertility, better understanding of underlying
      mechanisms, and exploration into avenues of treatment.

PMID- 20157306
TI  - Cerebrospinal fluid and plasma biomarkers in Alzheimer disease.
AB  - Intense multidisciplinary research has provided detailed knowledge of the
      molecular pathogenesis of Alzheimer disease (AD). This knowledge has been
      translated into new therapeutic strategies with putative disease-modifying
      effects. Several of the most promising approaches, such as amyloid-beta
      immunotherapy and secretase inhibition, are now being tested in clinical trials.
      Disease-modifying treatments might be at their most effective when initiated very
      early in the course of AD, before amyloid plaques and neurodegeneration become
      too widespread. Thus, biomarkers are needed that can detect AD in the predementia
      phase or, ideally, in presymptomatic individuals. In this Review, we present the
      rationales behind and the diagnostic performances of the core cerebrospinal fluid
      (CSF) biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino
      acid form of amyloid-beta. These biomarkers reflect AD pathology, and are
      candidate markers for predicting future cognitive decline in healthy individuals
      and the progression to dementia in patients who are cognitively impaired. We also
      discuss emerging plasma and CSF biomarkers, and explore new proteomics-based
      strategies for identifying additional CSF markers. Furthermore, we outline the
      roles of CSF biomarkers in drug discovery and clinical trials, and provide
      perspectives on AD biomarker discovery and the validation of such markers for use
      in the clinic.

PMID- 20157307
TI  - Environmental factors and their timing in adult-onset multiple sclerosis.
AB  - Multiple sclerosis (MS) is a common, complex neurological disease.
      Epidemiological data implicate both genetic and environmental factors in the
      etiology of MS, with various factors interacting with one another. Environmental
      exposures might occur long before the disease becomes clinically evident, as
      suggested by the wide range in onset age. In this Review, we examine the key time
      periods during which the environment might contribute to MS susceptibility, as
      well as the potential environmental factors involved. Understanding the nature of
      environmental influences in MS is highly relevant to the development of public
      health measures that are aimed at preventing this debilitating disease.

PMID- 20157309
TI  - Biological embedding of stress through inflammation processes in childhood.

PMID- 20157308
TI  - Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management.
AB  - Patients with acute ischemic stroke frequently test positive for hyperglycemia,
      which is associated with a poor clinical outcome. This association between poor
      glycemic control and an unfavorable prognosis is particularly evident in patients
      with persistent hyperglycemia, patients without a known history of diabetes
      mellitus, and patients with cortical infarction. To date, however, only one large
      clinical trial has specifically investigated the effect of glycemic control on
      stroke outcome. This trial failed to show a clinical benefit, but had several
      limitations. Despite a lack of clinical evidence supporting the use of glycemic
      control in the treatment of patients with stroke, international guidelines
      recommend treating this subset of critically ill patients for hyperglycemia in
      the hospital setting. This treatment regime is, however, particularly challenging
      in patients with stroke, and is associated with an increased risk of the patient
      developing hypoglycemia. Here we review the available evidence linking
      hyperglycemia to a poor clinical outcome in patients with ischemic stroke. We
      highlight the pathophysiological mechanisms that might underlie the deleterious
      effects of hyperglycemia on acute stroke prognosis and systematically review the
      literature concerning tight glycemic control after stroke. Finally, we provide
      directions on the use of insulin treatment strategies to control hyperglycemia in
      this patient group.

PMID- 20157310
TI  - A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD
      and predicts effectiveness of stimulant medication.
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability
      (0.8), suggesting that about 80% of phenotypic variance is due to genetic
      factors. We used the integration of statistical and functional approaches to
      discover a novel gene that contributes to ADHD. For our statistical approach, we
      started with a linkage study based on large multigenerational families in a
      population isolate, followed by fine mapping of targeted regions using a family
      based design. Family- and population-based association studies in five samples
      from disparate regions of the world were used for replication. Brain imaging
      studies were performed to evaluate gene function. The linkage study discovered a
      genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide
      samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical
      association of LPHN3 and ADHD was confirmed. Functional studies revealed that
      LPHN3 variants are expressed in key brain regions related to attention and
      activity, affect metabolism in neural circuits implicated in ADHD, and are
      associated with response to stimulant medication. Linkage and replicated
      association of ADHD with a novel non-candidate gene (LPHN3) provide new insights
      into the genetics, neurobiology, and treatment of ADHD.

PMID- 20157311
TI  - Life events moderate variation in cognitive ability (g) in adults.

PMID- 20157313
TI  - Seated reach distance and trunk excursion accurately reflect dynamic postural
      control in individuals with motor-incomplete spinal cord injury.
AB  - STUDY DESIGN: To determine whether kinematic measures of reach excursion are
      valid measures of postural control in individuals with motor-incomplete spinal
      cord injury (MISCI), seated reach test (SRT; obtained from a wrist marker) values
      and associated trunk excursion values (obtained from a C7 marker) were compared
      with center of pressure excursion (COPE). Data were obtained from individuals
      with MISCI and from non-disabled individuals for each of four directions. To
      assess the reliability of these measures in subjects with MISCI, these values
      were collected on two separate days. OBJECTIVE: Dynamic seated postural control
      is essential for individuals who perform their daily activities from a
      wheelchair. Although seated reach distance is used as a proxy measure for
      postural control, it is unknown whether this is an accurate and reliable measure
      of the limits of stability in individuals with MISCI. RESULTS: In subjects with
      MISCI, the SRT was significantly correlated with the COPE in three directions of
      reaching (r >= 0.71), with the exception being leftward reaching. Trunk excursion
      was correlated with COPE in all directions (r >= 0.93). In non-disabled
      individuals, both SRT (r >= 0.56) and trunk excursion (r >= 0.91) were correlated
      with COPE for all directions. In individuals with MISCI, there was significant
      intersession agreement for both reach distance (intraclass correlation
      coefficient (ICC)>= 0.78) and trunk excursion (ICC >= 0.77) measured in all
      directions. CONCLUSIONS: Although both SRT and trunk excursion are reasonable
      reflections of COPE, measurement of postural control based on trunk excursion has
      advantages for individuals who may have difficulty maintaining arm position
      during reaching. Reach distance is highly reliable in individuals with MISCI in
      all directions of reaching.

PMID- 20157312
TI  - Molecular pathways involved in neuronal cell adhesion and membrane scaffolding
      contribute to schizophrenia and bipolar disorder susceptibility.
AB  - Susceptibility to schizophrenia and bipolar disorder may involve a substantial,
      shared contribution from thousands of common genetic variants, each of small
      effect. Identifying whether risk variants map to specific molecular pathways is
      potentially biologically informative. We report a molecular pathway analysis
      using the single-nucleotide polymorphism (SNP) ratio test, which compares the
      ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway
      to identify the 'enrichment' for association signals. We applied this approach to
      the discovery (the International Schizophrenia Consortium (n=6909)) and
      validation (Genetic Association Information Network (n=2729)) of schizophrenia
      genome-wide association study (GWAS) data sets. We investigated each of the 212
      experimentally validated pathways described in the Kyoto Encyclopaedia of Genes
      and Genomes in the discovery sample. Nominally significant pathways were tested
      in the validation sample, and five pathways were found to be significant (P=0.03
      0.001); only the cell adhesion molecule (CAM) pathway withstood conservative
      correction for multiple testing. Interestingly, this pathway was also
      significantly associated with bipolar disorder (Wellcome Trust Case Control
      Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three
      samples (NRXN1 and CNTNAP2), which were previously implicated in specific
      language disorder, autism and schizophrenia. The CAM pathway functions in
      neuronal cell adhesion, which is critical for synaptic formation and normal cell
      signaling. Similar pathways have also emerged from a pathway analysis of autism,
      suggesting that mechanisms involved in neuronal cell adhesion may contribute
      broadly to neurodevelopmental psychiatric phenotypes.

PMID- 20157314
TI  - Upper limb reconstructive surgery uptake for persons with tetraplegia in New
      Zealand: a retrospective case review 2001-2005.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To describe the uptake of
      upper limb surgery by individuals with tetraplegia in New Zealand (NZ). SETTING:
      New Zealand. METHODS: The clinical notes of all individuals who sustained a
      cervical spinal cord injury between 1 January 2001 and 31 December 2005 were
      retrospectively reviewed for those who met the clinical criteria to undergo upper
      limb surgery. Cases were cross-referenced to the hand surgery record to determine
      the uptake of upper limb surgery in this cohort. RESULTS: The uptake of upper
      limb surgery for people with tetraplegia in NZ was 44% of the eligible cohort and
      59% of those assessed for surgery. This is notably higher than the reported
      proportion in other developed countries. The data also suggested that women and
      those who identified as NZ Maori were less likely to undergo upper limb surgery
      than were men and those of NZ European ethnicity. CONCLUSION: Utilization of
      upper limb surgery in the eligible tetraplegic population in NZ was high.
      However, it seemed that some groups were less likely to undergo surgery. Further
      research into the factors that affect an individual's decision to undergo upper
      limb surgery could explain the observed pattern.

PMID- 20157315
TI  - Subclinical atherosclerosis is related to injury level but not to inflammatory
      parameters in spinal cord injury subjects.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: Individuals with spinal cord injury
      (SCI) exhibit increased carotid intima-media thickness (IMT) and are reported to
      be exposed to higher circulating levels of inflammatory mediators. This study
      evaluated the relationship between inflammatory markers and carotid surrogates of
      cardiovascular risk in subjects with SCI. SETTING: Sao Paulo, Brazil. METHODS: A
      total of 65 nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI;
      31 healthy subjects) were evaluated by medical history, anthropometry, routine
      laboratory tests, analysis of hemodynamic, inflammatory parameters and ultrasound
      examination of carotid arteries. RESULTS: Subjects with SCI (18 tetraplegic and
      16 paraplegic) had lower systolic blood pressure (P = 0.009), higher serum C
      reactive protein (P = 0.001), tumor necrosis factor (TNF) receptor-II (P = 0.02)
      and TNF receptor-I (P = 0.04) levels and increased in vitro production of
      interleukin-6 by mononuclear cells (P = 0.04), compared to able-bodied
      individuals. No differences in serum interleukin-6, e-selectin, intercellular
      adhesion molecule-1, vascular cell adhesion molecule-1 and transforming growth
      factor-beta levels, or in vitro release of interleukin-10, interleukin-17 and
      interferon-gamma by mononuclear cells, were detected between the studied groups.
      Common carotid IMT, but not internal carotid resistive index, was significantly
      higher in subjects with SCI (P<0.0001 adjusted for C-reactive protein and TNF
      receptor-II levels). In addition, tetraplegic subjects exhibited increased IMT (P
      = 0.002 adjusted for systolic blood pressure and body mass index), but similar
      levels of inflammatory mediators compared to paraplegic ones. CONCLUSIONS:
      Individuals with SCI exhibit a clustering of vascular and inflammatory surrogates
      of increased cardiovascular risk. Nevertheless, subclinical carotid
      atherosclerosis is related to injury level but not to increased inflammatory
      status in these subjects.

PMID- 20157316
TI  - Compensation or displacement of physical activity in middle-school girls: the
      Trial of Activity for Adolescent Girls.
AB  - OBJECTIVE: The 'activitystat' hypothesis suggests that increases in moderate-to
      vigorous physical activity (MVPA) are accompanied by a compensatory reduction in
      light physical activity (LPA) and/or an increase in inactivity to maintain a
      consistent total physical activity level (TPA). The purpose of this study was to
      identify the evidence of compensation in middle-school girls. SUBJECTS:
      Participants were 6916, 8th grade girls from the Trial of Activity for Adolescent
      Girls (TAAG). DESIGN: Inactivity and physical activity were measured over 6-
      consecutive days using accelerometry (MTI Actigraph). A within-girl, repeated
      measures design was used to assess associations between physical activity and
      inactivity using general linear mixed models. RESULTS: Within a given day, for
      every one MET-minute more of inactivity, there was 3.18 MET-minutes (95%
      confidence interval (CI): -3.19, -3.17) less of TPA (activity >2 METS) on the
      same day. Daily inactivity was also negatively associated with TPA on the
      following day. Each additional minute of MVPA was associated with 1.85 min less
      of inactivity on the same day (95% CI: -1.89, -1.82). Daily MVPA was also
      negatively associated with inactivity the following day. CONCLUSION: Our results,
      based on 6 days of observational data, were not consistent with the
      'activitystat' hypothesis, and instead indicated that physical activity displaced
      inactivity, at least in the short term. Longer intervention trials are needed,
      nevertheless our findings support the use of interventions to increase physical
      activity over discrete periods of time in middle-school girls.

PMID- 20157317
TI  - Western diet increases wheel running in mice selectively bred for high voluntary
      wheel running.
AB  - OBJECTIVE: Mice from a long-term selective breeding experiment for high voluntary
      wheel running offer a unique model to examine the contributions of genetic and
      environmental factors in determining the aspects of behavior and metabolism
      relevant to body-weight regulation and obesity. Starting with generation 16 and
      continuing through to generation 52, mice from the four replicate high runner
      (HR) lines have run 2.5-3-fold more revolutions per day as compared with four non
      selected control (C) lines, but the nature of this apparent selection limit is
      not understood. We hypothesized that it might involve the availability of dietary
      lipids. METHODS: Wheel running, food consumption (Teklad Rodent Diet (W) 8604,
      14% kJ from fat; or Harlan Teklad TD.88137 Western Diet (WD), 42% kJ from fat)
      and body mass were measured over 1-2-week intervals in 100 males for 2 months
      starting 3 days after weaning. RESULTS: WD was obesogenic for both HR and C,
      significantly increasing both body mass and retroperitoneal fat pad mass, the
      latter even when controlling statistically for wheel-running distance and caloric
      intake. The HR mice had significantly less fat than C mice, explainable
      statistically by their greater running distance. On adjusting for body mass, HR
      mice showed higher caloric intake than C mice, also explainable by their higher
      running. Accounting for body mass and running, WD initially caused increased
      caloric intake in both HR and C, but this effect was reversed during the last
      four weeks of the study. Western diet had little or no effect on wheel running in
      C mice, but increased revolutions per day by as much as 75% in HR mice, mainly
      through increased time spent running. CONCLUSION: The remarkable stimulation of
      wheel running by WD in HR mice may involve fuel usage during prolonged endurance
      exercise and/or direct behavioral effects on motivation. Their unique behavioral
      responses to WD may render HR mice an important model for understanding the
      control of voluntary activity levels.

PMID- 20157318
TI  - A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet
      induced obese mice.
AB  - OBJECTIVE: A sexual dimorphism exists in body fat distribution; females deposit
      relatively more fat in subcutaneous/inguinal depots whereas males deposit more
      fat in the intra-abdominal/gonadal depot. Our objective was to systematically
      document depot- and sex-related differences in the accumulation of adipose tissue
      and gene expression, comparing differentially expressed genes in diet-induced
      obese mice with mice maintained on a chow diet. RESEARCH DESIGN AND METHODS: We
      used a microarray approach to determine whether there are sexual dimorphisms in
      gene expression in age-matched male, female or ovariectomized female (OVX)
      C57/BL6 mice maintained on a high-fat (HF) diet. We then compared expression of
      validated genes between the sexes on a chow diet. RESULTS: After exposure to a
      high fat diet for 12 weeks, females gained less weight than males. The microarray
      analyses indicate in intra-abdominal/gonadal adipose tissue in females 1642 genes
      differ by at least twofold between the depots, whereas 706 genes differ in
      subcutaneous/inguinal adipose tissue when compared with males. Only 138 genes are
      commonly regulated in both sexes and adipose tissue depots. Inflammatory genes
      (cytokine-cytokine receptor interactions and acute-phase protein synthesis) are
      upregulated in males when compared with females, and there is a partial reversal
      after OVX, where OVX adipose tissue gene expression is more 'male-like'. This
      pattern is not observed in mice maintained on chow. Histology of male gonadal
      white adipose tissue (GWAT) shows more crown-like structures than females,
      indicative of inflammation and adipose tissue remodeling. In addition, genes
      related to insulin signaling and lipid synthesis are higher in females than
      males, regardless of dietary exposure. CONCLUSIONS: These data suggest that male
      and female adipose tissue differ between the sexes regardless of diet. Moreover,
      HF diet exposure elicits a much greater inflammatory response in males when
      compared with females. This data set underscores the importance of analyzing
      depot-, sex- and steroid-dependent regulation of adipose tissue distribution and
      function.

PMID- 20157319
TI  - Fat oxidation at rest predicts peak fat oxidation during exercise and metabolic
      phenotype in overweight men.
AB  - OBJECTIVE: To elucidate if fat oxidation at rest predicts peak fat oxidation
      during exercise and/or metabolic phenotype in moderately overweight, sedentary
      men. DESIGN: Cross-sectional study. SUBJECTS: We measured respiratory exchange
      ratio (RER) at rest in 44 moderately overweight, normotensive and normoglycemic
      men and selected 8 subjects with a low RER (L-RER, body mass index (BMI): 27.9+/
      0.9 kg m(-2), RER: 0.76+/-0.02) and 8 with a high RER (H-RER; BMI 28.1+/-1.1 kg
      m(-2), RER: 0.89+/-0.02). After an overnight fast, a venous blood sample was
      obtained and a graded exercise test was performed. Fat oxidation during exercise
      was quantified using indirect calorimetry. RESULTS: Peak fat oxidation during
      exercise was higher in L-RER than in H-RER (0.333+/-0.096 vs 0.169+/-0.028 g min(
      1); P<0.01) and occurred at a higher relative intensity (36.2+/-6.6 vs 28.2+/
      3.1% VO(2max), P<0.05). Using the International Diabetes Federation criteria, we
      found that there was a lower accumulation of metabolic risk factors in L-RER than
      in H-RER (1.6 vs 3.5, P=0.028), and no subjects in L-RER and four of eight
      subjects in H-RER had the metabolic syndrome. Resting RER was positively
      correlated with plasma triglycerides (P<0.01) and negatively with plasma free
      fatty acids (P<0.05), and peak fat oxidation during exercise was positively
      correlated with plasma free fatty acid concentration at rest (P<0.05).
      CONCLUSION: A low RER at rest predicts a high peak fat oxidation during exercise
      and a healthy metabolic phenotype in moderately overweight, sedentary men.

PMID- 20157320
TI  - Metabolic syndrome as a risk factor for high-ocular tension.
AB  - OBJECTIVE: To investigate the relationship between the metabolic syndrome and
      intraocular pressure (IOP). METHODS: An observational study was conducted in a
      medical health checkup program at a general hospital. This study involved 14 003
      apparently healthy Japanese men and women, 18-83 years of age, with a mean IOP of
      14.8 (3.0) mm Hg. IOP was examined by noncontact tonometer. High-ocular tension
      was defined as IOP >21 mm Hg without optic-disc abnormalities or history of
      receiving any anti-glaucoma therapy. Modified criteria of the revised National
      Cholesterol Education Program Adult Treatment Panel III (rATPIII), the new
      International Diabetes Federation definition, and the Japan Society for The Study
      of Obesity definition were used to characterize the metabolic syndrome. Air
      temperature was assessed from the Gifu Meteorological Observatory, Gifu, Japan.
      RESULTS: In the male and female subjects, mean IOP and the prevalence of high
      ocular tension became high in direct correlation with the increased number of
      metabolic syndrome components. To analyze by logistic regression, the metabolic
      syndrome defined by rATPIII was positively and maximum temperature was negatively
      correlated with high-ocular tension in males (adjusted odds ratio: 2.0 [95%
      confidence interval, CI, 1.43-2.78] and 0.63 [95% CI, 0.54-0.73], respectively)
      and in females (adjusted odds ratio: 7.09 [95% CI, 3.74-13.43] and 0.67 [95% CI,
      0.53-0.87], respectively). Three of five metabolic syndrome components (fasting
      plasma glucose, blood pressure, and triglycerides) were related to high-ocular
      tension. CONCLUSION: The metabolic syndrome is a risk factor for high-ocular
      tension.

PMID- 20157321
TI  - Identification of cardiovascular genes in omentum from morbidly obese patients
      with type 2 diabetes.
AB  - BACKGROUND: The metabolic syndrome describes the association between obesity and
      co-morbidities including insulin resistance, hypertension, dyslipidemia, and
      cardiovascular (CV) disease. Adipokines produced from omentum contribute to the
      risk of CV disease and increase the inflammatory state. This study examines the
      gene expression differences in the omental tissue of morbidly obese diabetic and
      non-diabetic patients. METHODS: Twenty morbidly obese patients undergoing
      bariatric surgery were included. Ten patients were diabetic and 10 were non
      diabetic. Omental samples were collected intraoperatively and snap frozen. Total
      RNA was extracted using the Trizol reagent and purified with the RNeasy kit
      (Qiagen). Microarray experiments were performed using the Affymetrix Gene 1.0 ST
      array and data was analyzed with the Partek 6.3 program using an unpaired t-test
      (P<0.05). The gene expression profiles of the diabetic group were compared with
      the non-diabetic group. Using the Ingenuity program, the gene list generated from
      the microarray analysis was evaluated and real-time quantitative PCR (qPCR) was
      used to validate the array data. RESULTS: Compared with the non-diabetic group,
      the diabetic obese patients showed 79 upregulated genes and 4 downregulated genes
      with >1.4-fold difference in expression. Ingenuity analysis showed numerous
      dysregulated genes associated with CV disease including leptin, Von Willebrand
      factor, P-selectin, angiopoietin-1 (ANGPT1), phospholipase A2 (group VII), and
      periostin osteoblast specific factor. Microarray results for the earlier
      mentioned genes were confirmed with qPCR. The results were analyzed with respect
      to the presence or absence of hyperlipidemia, hypertension, and coronary artery
      disease. In patients with hyperlipidemia, ANGPT1 and P-selectin were upregulated
      1.9- and 2.9-fold, respectively. CONCLUSIONS: This microarray analysis of omental
      tissue from morbidly obese diabetic patients documents a host of upregulated
      genes related to CV disease. This study provides further evidence that diabetic
      status predisposes obese patients to a higher risk of developing CV disease.

PMID- 20157322
TI  - Self-reported binge eating in severe pediatric obesity: impact on weight change
      in a randomized controlled trial of family-based treatment.
AB  - OBJECTIVE: This study sought to document self-reported binge eating in a large
      sample of severely obese children and to examine the impact of binge eating on
      changes in percent overweight among children randomized to family-based
      behavioral treatment (intervention) versus control (usual care). PARTICIPANTS AND
      METHODS: As part of a larger randomized controlled trial, 192 children aged 8-12
      years (M=10.2, s.d.=1.2) with a mean body mass index (BMI) percentile of 99.2
      (s.d.=0.7) completed assessments at baseline and 6-, 12-, and 18 months post
      randomization. A parent or guardian also participated. Child psychological
      symptoms, including binge eating, were measured before randomization using self
      report questionnaires. Child height and weight were measured at baseline, 6-, 12
      , and 18 months. The primary study outcome was percent overweight (that is,
      percent over median BMI for age and sex). RESULTS: Twenty-two children (11.5%)
      endorsed binge eating at baseline (Binge Eating Group). Children in the Binge
      Eating Group were younger and had more depressive, anxiety, and eating disorder
      symptoms, and lower self-esteem than children in the rest of the sample (No Binge
      Eating Group). There also were differences between the Binge Eating and No Binge
      Eating groups with respect to the short-term effects of treatment group
      assignment on change in percent overweight during the study. Specifically,
      improvements in percent overweight in the intervention condition relative to
      usual care were documented in the No Binge Eating Group only. Among children in
      the Binge Eating Group, those assigned to intervention showed a 2.6% increase in
      percent overweight, on average, at the completion of acute treatment as compared
      to an 8.5% decrease among children without binge eating. However, these effects
      were not maintained during follow-up. CONCLUSION: Results of this study suggest
      the importance of considering binge eating in the development of weight
      management programs for severely obese youth.

PMID- 20157323
TI  - A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse
      agonist, in obese and overweight patients: a high-dose study.
AB  - OBJECTIVE: To evaluate the efficacy, safety and tolerability of taranabant in
      obese and overweight patients. DESIGN: Double-blind, randomized, placebo
      controlled study. SUBJECTS: Patients were >or=18 years old, with body mass index
      of 27-43 kg m(-2), and 51% with metabolic syndrome (MS) randomized to placebo
      (N=417) or taranabant 2 mg (N=414), 4 mg (N=415) or 6 mg (N=1256) for 104 weeks.
      MEASUREMENTS: Key efficacy measurements included body weight, waist circumference
      (WC), lipid and glycemic end points. RESULTS: On the basis of risk/benefit
      assessments, the 6-mg dose was discontinued during year 1 (patients on 6 mg were
      down-dosed to 2 mg or placebo) and the 4-mg dose was discontinued during year 2
      (patients on 4 mg were down-dosed to 2 mg). Changes from baseline in body weight
      at week 52 (all-patients-treated population, last observation carried forward
      analysis) were -2.6, -6.6 and -8.1 kg, respectively, for placebo and taranabant 2
      and 4 mg (both doses P<0.001 vs placebo). For patients who completed year 1,
      changes from baseline in body weight at week 104 were -1.4, -6.4 and -7.6 kg for
      placebo and taranabant 2 and 4 mg, respectively (both doses P<0.001 vs placebo).
      The proportions of patients at weeks 52 and 104 who lost at least 5 and 10% of
      their baseline body weight were significantly higher and the proportions of
      patients who met criteria for MS were significantly lower for taranabant 2 and 4
      mg vs placebo. The incidence of adverse experiences classified in the
      gastrointestinal, nervous, psychiatric, cutaneous and vascular organ systems were
      generally observed to be dose related with taranabant vs placebo. CONCLUSION:
      Taranabant at the 2- and 4-mg dose was effective in achieving clinically
      significant weight loss over 2 years and was associated with dose-related
      increases in adverse experiences. On the basis of these and other data, an
      assessment was made that the overall safety and efficacy profile of taranabant
      did not support its further development for the treatment of obesity.

PMID- 20157324
TI  - Changes in BMI over 6 years: the role of demographic and neighborhood
      characteristics.
AB  - OBJECTIVE: To undertake a 6-year longitudinal investigation of the relationship
      between the built environment (perceived and objectively measured) and change in
      body mass index (BMI). Specifically, this research examined whether change in BMI
      was predicted by objectively measured neighborhood walkability and socioeconomic
      status (SES), and perceived neighborhood characteristics (for example, crime,
      traffic and interesting things to look at) in addition to other factors such as
      age, gender, education, physical activity, fruit and vegetable consumption and
      smoking. DESIGN: Longitudinal study. SUBJECTS: 500 adults who provided complete
      data in 2002 and 2008 and who did not move over the course of the study (47.8%
      female; age in 2002: 18-90 years). MEASUREMENTS: Telephone surveys in 2002 and
      2008 measuring perceptions of their neighborhood environment and demographic
      factors. Objective measures of neighborhood characteristics were calculated using
      census data and geographical information systems in 2006. RESULTS: Age,
      neighborhood SES and perceived traffic were significantly related to increased
      BMI over the 6 years. Younger participants and those in lower SES neighborhoods
      were more likely to have increased BMI. Agreement with the statement that traffic
      made it difficult to walk also predicted increased BMI. CONCLUSION: This study
      adds to the literature to show that BMI increased in low SES neighborhoods.
      Although more research is needed to fully understand how neighborhood SES
      contributes to obesity, it is without question that individuals in socially
      disadvantaged neighborhoods face more barriers to health than their wealthier
      counterparts. This study also calls into question the relationship between
      walkability and changes in BMI and emphasizes the necessity of longitudinal data
      rather than relying on cross-sectional research.

PMID- 20157325
TI  - Leptin intake during the suckling period improves the metabolic response of
      adipose tissue to a high-fat diet.
AB  - BACKGROUND: The intake of leptin during the suckling period protects against
      obesity and improves insulin and central leptin sensitivity in adult rats.
      OBJECTIVE: We analyzed whether leptin treatment to neonates may also improve
      later peripheral leptin sensitivity in adipose tissue under high-fat (HF) diet
      conditions. DESIGN: Male rats were supplemented with a daily oral dose of leptin
      or the vehicle (controls) during the suckling period. After weaning, animals were
      fed a normal-fat or an HF diet until the age of 6 months. At this age, mRNA and
      protein levels of the long-form leptin receptor (OB-Rb) and the expression of
      other genes related with energy metabolism were measured in various adipose
      depots (inguinal, mesenteric and retroperitoneal). RESULTS: HF-diet feeding
      resulted in lower OB-Rb mRNA and protein levels in internal depots in controls
      but not in leptin-treated animals; these animals maintained OB-Rb mRNA and
      protein levels under HF-diet conditions in these depots, particularly in the
      mesenteric one, and this was accompanied by increased expression of genes related
      with energy uptake (GLUT4, CD36), fatty acid oxidation (peroxisome proliferator
      activated receptor-alpha (PPARalpha), CPT1, UCP3) and lipogenesis (PPARgamma,
      GPAT). Leptin-treatment also ameliorated HF-diet-induced hepatic fat accumulation
      occurring in control animals. CONCLUSION: Leptin treatment during the suckling
      period may improve the lasting effects of HF-diet feeding on leptin receptor
      abundance in the adipose tissue and increase its oxidative capacity, resulting in
      a better handling and partitioning of excess fuel. This, together with the
      described improvement of central leptin sensitivity, may explain why these
      animals are more protected against diet-induced obesity and its metabolic-related
      disorders.

PMID- 20157326
TI  - Effects of increasing dietary protein and fibre intake with lupin on body weight
      and composition and blood lipids in overweight men and women.
AB  - BACKGROUND: Lupin kernel flour (LKF) is a novel food ingredient that is high in
      protein and fibre. We have previously shown that partial substitution of refined
      wheat-derived carbohydrate in bread with protein and fibre from LKF can reduce
      appetite and energy intake acutely. In addition, several studies have suggested
      that lupin may reduce cholesterol concentrations and benefit glucose and insulin
      metabolism. AIM: The aim of this study was to investigate the effects on body
      weight and composition and blood lipids, glucose and insulin of an ad libitum LKF
      enriched diet higher in dietary protein and fibre. SUBJECTS AND METHODS: A total
      of 88 overweight and obese men and women were recruited for a 16-week parallel
      design randomized controlled trial. Participants replaced 15-20% of their usual
      daily energy intake with white bread (control) or LKF-enriched bread (lupin) in
      an ad libitum diet. Measurements of body weight and composition, and fasting
      blood biochemical measurements were performed at baseline and 16 weeks. The
      primary analysis included 74 participants (37 per group) who completed the
      intervention. RESULTS: At baseline, mean (+/-s.d.) body mass index and total
      cholesterol were 30.6+/-3.5 kg m(-2) and 5.37+/-0.94 mmol l(-1), respectively.
      Estimated (mean between-group difference (95% confidence interval)) protein (13.7
      (2.28, 25.0) g per day) and fibre (12.5 (8.79, 16.2) g per day) intakes were
      higher during the intervention with lupin than with control. For lupin relative
      to control, the net effects on body weight (-0.4 (-1.3, 0.6) kg), fat mass (-0.5
      (-1.1, 0.2) kg) and percentage (-0.5 (-1.1, 0.1)%), plasma leptin (-1.66 (-4.91,
      1.59) ng ml(-1)) and adiponectin (0.20 (-0.73, 1.13) mg l(-1), as well as serum
      total cholesterol (-0.08 (-0.38, 0.22) mmol l(-1)), triglycerides (0.09 (-0.10,
      0.21) mmol l(-1)), glucose (0.10 (-0.11, 0.30) mmol l(-1)) and insulin (0.40 (
      1.20, 2.00) mU l(-1)) were not significant. CONCLUSIONS: This study does not
      support the proposal that an ad libitum diet enriched in LKF resulting in
      moderate changes in both protein and fibre intakes can benefit body weight and
      composition or fasting blood lipids, glucose and insulin concentrations in
      overweight men and women with mildly elevated total cholesterol concentrations.

PMID- 20157328
TI  - What determines Th2 differentiation, in vitro and in vivo?
AB  - We have known since 1991 how to induce naive CD4 T cells to differentiate in
      vitro into Th2 cells and, over the ensuing years, a comprehensive picture of the
      molecules involved in this important process has emerged. GATA3 and STAT5 are
      both essential for in vitro differentiation, stimulating naive cells through a
      process involving induction, which is T-cell receptor (TCR) dependent but
      interleukin (IL)-4 independent, and commitment, which is IL-4 dependent. Th2
      differentiation in vivo appears more complex. GATA3 and probably STAT5 are
      required in vivo but, at least for certain helminth infections, the IL-4/IL
      4Ra/STAT6 pathway is dispensable. The role of thymic stromal lymphopoietin and of
      low TCR signal strength and the participation of basophils in establishing a Th2
      baising in vivo environment have achieved considerable attention. Here I discuss
      the major players in Th2 differentiation particularly as they may exert their
      effects in vivo.

PMID- 20157329
TI  - Autophagy gets the 'NOD' to enhance bacterial handling and antigen presentation.

PMID- 20157327
TI  - A variant near the interleukin-6 gene is associated with fat mass in Caucasian
      men.
AB  - CONTEXT: Regulation of fat mass appears to be associated with immune functions.
      Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress
      mature-onset obesity. OBJECTIVE: To systematically investigate associations of
      single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor
      (IL6R) genes with body fat mass, in support for our hypothesis that variants of
      these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The
      Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population
      based cross-sectional study of 18- to 20-year-old men (n=1049), from the
      Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts
      consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden
      (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME:
      The genotype distributions and their association with fat mass in different
      compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18
      evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP
      rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively
      associated with the primary outcome total body fat mass (effect size -0.11
      standard deviation (s.d.) units per A allele, P=0.02). This negative association
      with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts
      (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were
      combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative
      association with total body fat mass (effect size -0.05 s.d. units per A allele,
      P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass
      index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the
      other SNPs investigated in the GOOD study were reproducibly associated with body
      fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with
      decreased fat mass in three combined cohorts of 8927 Caucasian men.

PMID- 20157330
TI  - Queries about vaccines containing squalene.

PMID- 20157331
TI  - SNPs in genes coding for ROS metabolism and signalling in association with
      docetaxel clearance.
AB  - The dose of docetaxel is currently calculated based on body surface area and does
      not reflect the pharmacokinetic, metabolic potential or genetic background of the
      patients. The influence of genetic variation on the clearance of docetaxel was
      analysed in a two-stage analysis. In step one, 583 single-nucleotide
      polymorphisms (SNPs) in 203 genes were genotyped on samples from 24 patients with
      locally advanced non-small cell lung cancer. We found that many of the genes
      harbour several SNPs associated with clearance of docetaxel. Most notably these
      were four SNPs in EGF, three SNPs in PRDX4 and XPC, and two SNPs in GSTA4,
      TGFBR2, TNFAIP2, BCL2, DPYD and EGFR. The multiple SNPs per gene suggested the
      existence of common haplotypes associated with clearance. These were confirmed
      with detailed haplotype analysis. On the basis of analysis of variance (ANOVA),
      quantitative mutual information score (QMIS) and Kruskal-Wallis (KW) analysis
      SNPs significantly associated with clearance of docetaxel were confirmed for
      GSTA4, PRDX4, TGFBR2 and XPC and additional putative markers were found in
      CYP2C8, EPHX1, IGF2, IL1R2, MAPK7, NDUFB4, TGFBR3, TPMT (2 SNPs), (P<0.05 or
      borderline significant for all three methods, 14 SNPs in total). In step two,
      these 14 SNPs were genotyped in additional 9 samples and the results combined
      with the genotyping results from the first step. For 7 of the 14 SNPs, the
      results are still significant/borderline significant by all three methods: ANOVA,
      QMIS and KW analysis strengthening our hypothesis that they are associated with
      the clearance of docetaxel.

PMID- 20157332
TI  - C/EBPalpha regulates SIRT1 expression during adipogenesis.
AB  - SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in
      adipogenesis is largely unknown. In this study, we show that both SIRT1 protein
      and mRNA levels were increased along with CCAAT/enhancer-binding protein alpha
      (C/EBPalpha) during adipocyte differentiation. C/EBPalpha, but not C/EBPalphap30,
      activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes.
      Furthermore, C/EBPalpha upregulated SIRT1 mRNA and protein levels in HeLa cells
      and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In
      preadipocytes, ectopic expression of C/EBPalpha upregulated SIRT1 protein level
      and knockdown of C/EBPalpha led to the decrease of SIRT1 protein level. Moreover,
      by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation,
      we found that C/EBPalpha bound to the SIRT1 promoter at a consensus C/EBPalpha
      binding site. These data demonstrate that C/EBPalpha regulates SIRT1 expression
      during adipogenesis by directly binding to the SIRT1 promoter.

PMID- 20157333
TI  - Length of the ORF, position of the first AUG and the Kozak motif are important
      factors in potential dual-coding transcripts.
AB  - A single mammalian transcript normally encodes one protein, but the transcript of
      GNAS (G-protein alpha-subunit) contains two reading frames and produces two
      structurally unrelated proteins, XLalphas and ALEX. No other confirmed GNAS-like
      dual-coding transcripts have been reported to date, even though many such
      candidate genes have been predicted by bioinformatics analysis. In this study, we
      constructed a series of vectors to test how two protein products were translated
      from a single transcript in vitro. The length of the ORF (open reading frame),
      position of the first AUG and the Kozak motif were found to be important factors.
      These factors, as well as 55-bp NMD (nonsense-mediated mRNA decay) rule, were
      used in a bioinformatics search for candidate dual-coding transcripts. A total of
      1307, 750 and 474 two-ORF-containing transcripts were found in human, mouse and
      rat, respectively, of which 170, 89 and 70, respectively, were found to be
      potential dual-coding transcripts. Most transcripts showed low conservation among
      species. Interestingly, dual-coding transcripts were significantly enriched for
      transcripts from the zinc-finger protein family, which are usually DNA-binding
      proteins involved in regulation of the transcription process.

PMID- 20157334
TI  - Efficient and rapid generation of induced pluripotent stem cells using an
      alternative culture medium.

PMID- 20157335
TI  - Taming the next-gen beast.
AB  - This month's Genome Watch discusses how alternative approaches to using second
      generation sequencing technologies are powerful tools for the analysis of common
      pathogenic bacteria.

PMID- 20157337
TI  - Regulation of the replication cycle: conserved and diverse regulatory systems for
      DnaA and oriC.
AB  - Chromosomal replication must be limited to once and only once per cell cycle.
      This is accomplished by multiple regulatory pathways that govern initiator
      proteins and replication origins. A principal feature of DNA replication is the
      coupling of the replication reaction to negative-feedback regulation. Some of the
      factors that are important in this process have been discovered, including the
      clamp (DNA polymerase III subunit-beta (DnaN)), the datA locus, SeqA, DnaA
      homologue protein (Hda) and YabA, as well as factors that are involved at other
      stages of the regulatory mechanism, such as DnaA initiator-associating protein
      (DiaA), the DnaA-reactivating sequence (DARS) loci and Soj. Here, we describe the
      regulation of DnaA, one of the central proteins involved in bacterial DNA
      replication, by these factors in Escherichia coli, Bacillus subtilis and
      Caulobacter crescentus.

PMID- 20157338
TI  - Host interactions of probiotic bacterial surface molecules: comparison with
      commensals and pathogens.
AB  - How can probiotic bacteria transduce their health benefits to the host? Bacterial
      cell surface macromolecules are key factors in this beneficial microorganism-host
      crosstalk, as they can interact with host pattern recognition receptors (PRRs) of
      the gastrointestinal mucosa. In this Review, we highlight the documented
      signalling interactions of the surface molecules of probiotic bacteria (such as
      long surface appendages, polysaccharides and lipoteichoic acids) with PRRs.
      Research on host-probiotic interactions can benefit from well-documented host
      microorganism studies that span the spectrum from pathogenicity to mutualism.
      Distinctions and parallels are therefore drawn with the interactions of similar
      molecules that are presented by gastrointestinal commensals and pathogens.

PMID- 20157341
TI  - Synthesis of Biotinylated Tumor-Associated Carbohydrate Antigens for
      Immunological Studies.
AB  - Syntheses of several biotinylated human cancer-associated carbohydrate antigens
      for immunological studies are described.

PMID- 20157339
TI  - The population genetics of commensal Escherichia coli.
AB  - The primary habitat of Escherichia coli is the vertebrate gut, where it is the
      predominant aerobic organism, living in symbiosis with its host. Despite the
      occurrence of recombination events, the population structure is predominantly
      clonal, allowing the delineation of major phylogenetic groups. The genetic
      structure of commensal E. coli is shaped by multiple host and environmental
      factors, and the determinants involved in the virulence of the bacteria may in
      fact reflect adaptation to commensal habitats. A better characterization of the
      commensal niche is necessary to understand how a useful commensal can become a
      harmful pathogen. In this Review we describe the population structure of
      commensal E. coli, the factors involved in the spread of different strains, how
      the bacteria can adapt to different niches and how a commensal lifestyle can
      evolve into a pathogenic one.

PMID- 20157342
TI  - A simple and expedient method for the preparation of N-chlorohydantoins.
AB  - A simple and efficient methodology for the preparation of N-chlorinated
      hydantoins is presented. These versatile chlorenium sources were isolated in high
      yield after a simple recrystallization. Among the ten examples are the first
      chiral N-chlorohydantoins.

PMID- 20157340
TI  - A complex journey: transmission of microbial symbionts.
AB  - The perpetuation of symbioses through host generations relies on symbiont
      transmission. Horizontally transmitted symbionts are taken up from the
      environment anew by each host generation, and vertically transmitted symbionts
      are most often transferred through the female germ line. Mixed modes also exist.
      In this Review we describe the journey of symbionts from the initial contact to
      their final residence. We provide an overview of the molecular mechanisms that
      mediate symbiont attraction and accumulation, interpartner recognition and
      selection, as well as symbiont confrontation with the host immune system. We also
      discuss how the two main transmission modes shape the evolution of the symbiotic
      partners.

PMID- 20157343
TI  - Tuning the Thickness and Orientation of Single Au Pyramids for Improved
      Refractive Index Sensitivities.
AB  - This paper describes three ways to tune the multipolar surface plasmon resonances
      of Au pyramidal particles: (1) by varying their thickness; (2) by controlling
      their relative orientation on a surface; and (3) by changing the refractive index
      of the surrounding media. We found that as the index of the medium was increased
      that the plasmon resonances red-shifted linearly from visible to near infrared
      wavelengths. By screening the different geometric parameters, we found that 25-nm
      thick pyramids in a tip-up orientation produced the largest refractive index
      sensitivities.

PMID- 20157344
TI  - Synthesis of the Naturally Occurring (-)-1,3,5-Tri-O-Caffeoylquinic Acid.
AB  - Ribonuclease H (RNase H) is an essential component to the replication of human
      immunodeficiency virus (HIV), and only a few inhibitors of this enzyme are known.
      Millenia Hope Pharmaceuticals Inc. found that (-)-1,3,5-tri-O-caffeoylquinic acid
      is a potent RNase H inhibitor and antiviral agent. A facile route leading to this
      inhibitor from commercially available (-)-quinic acid is reported within.

PMID- 20157345
TI  - Perfluorocarbon-loaded Shell Crosslinked Knedel-like Nanoparticles: Lessons
      regarding polymer mobility and self assembly.
AB  - Reversible addition-fragmentation chain transfer polymerization was employed to
      synthesize a set of copolymers of styrene (PS) and 2,3,4,5,6-pentafluorostyrene
      (PPFS), as well as block copolymers with tert-butyl acrylate (PtBA)-b-PS-co-PPFS,
      with control over molecular weight and polydispersity. It was found that the
      copolymerization of styrene and PFS allowed for the preparation of gradient
      copolymers with opposite levels of monomer consumption, depending on the feed
      ratio. Conversion to amphiphilic block copolymers, PAA-b-(PS-co-PPFS), by
      removing the protecting groups was followed by fitting with monomethoxy
      poly(ethylene glycol) chains. Solution-state assembly and intramicellar
      crosslinking afforded shell crosslinked (SCK) block copolymer nanoparticles.
      These fluorinated nanoparticles (ca. 20 nm diameters) were studied as potential
      magnetic resonance imaging (MRI) contrast agents based on the (19)F-nuclei,
      however, it was found that packaging of the hydrophobic fluorinated polymers into
      the core domain restricted the mobility of the chains and prohibited (19)F-NMR
      spectroscopy when the particles were dispersed in water without an organic
      cosolvent. Packing of perflouro-15-crown-5-ether (PFCE) into the polymer micelle
      was demonstrated with good uptake efficiency, however, it was necessary to swell
      the core with a good solvent (DMSO) to increase the mobility and observe the
      (19)F-NMR signal of the PFCE.

PMID- 20157346
TI  - Biological Resource Centers and Systems Biology.
AB  - There are hundreds of Biological Resource Centers (BRCs) around the world,
      holding many little-studied microorganism. The proportion of bacterial strains
      that is well represented in the sequence and literature databases may be as low
      as 1%. This body of unexplored diversity represents an untapped source of useful
      strains and derived products. However, a modicum of phenotypic data is available
      for almost all the bacterial strains held by BRCs around the world. It is at the
      phenotypic level that our knowledge of the well-studied strains of bacteria and
      the many yet-to-be studied strains intersects. This suggests we might leverage
      the phenotypic data from the data-poor bacteria with the omics data from the data
      rich bacteria, using our knowledge of their evolutionary relationships, to map
      the metabolic networks of the little-known bacteria. This systems biology-based
      approach is a new way to explore the diversity harbored in BRCs.

PMID- 20157347
TI  - Associations of Psychosocial Factors with Maternal Confidence Among Japanese and
      Vietnamese Mothers.
AB  - We conducted this cross-sectional study among 392 Japanese and 294 Vietnamese
      mothers who attended routine child health visits in a Japanese city and at a
      tertiary hospital in Vietnam, in order to investigate the prevalence and
      associated sociodemographic, parenting, and psychological characteristics of low
      maternal confidence in child rearing among them. All data were collected from
      medical files in Japan, and from medical files and self-administered
      questionnaires in Vietnam. The proportion of mothers without secure feeling of
      confidence in the present study was 22% in Japan and 66% in Vietnam. Significant
      factors associated with a lack of confidence were first-time motherhood and
      unintended pregnancy in the Japanese dataset and younger age in the Vietnamese
      dataset. In both groups, a higher proportion of mothers who lacked confidence
      reported negative parenting outcomes than did confident mothers. Among the three
      psychological measurements (mood, self-efficacy and depression), higher self
      efficacy was associated independently with a significantly reduced risk of not
      having confidence in child rearing. These results suggest the importance of
      developing parenting support programs to help Japanese and Vietnamese mothers,
      particularly those who are young, first-time mothers or who became pregnant
      unexpectedly, improve their self-efficacy.

PMID- 20157348
TI  - Archives of Drug Information-A New Approach to Publishing the Results of Drug
      Studies.
AB  - Current scientific publishing uses a selective, slow, and adversarial editorial
      process to publish a minority of papers submitted, and thus maximize a journal's
      impact factor, a major measure of success. However, the results of many
      pharmaceutical industry studies are deemed low priority and are therefore
      difficult or impossible to publish in scientific journals. Society is poorly
      served because access to the results of these studies is in the public interest.
      Archives of Drug Information is an independent, online only journal that will
      publish papers that are free of bias and that provide new information about a
      drug. Articles that would not usually be published by traditional journals, for
      example articles reporting negative studies, studies reporting animal toxicity or
      Phase I human studies, or routine pharmacokinetic or drug interaction studies are
      welcome. The editorial process will be rapid and user friendly. The contents of
      the journal will be available freely to all. Archives of Drug Information will
      allow the pharmaceutical industry to publish the results of studies and make
      freely accessible to the public the results of research studies that would
      otherwise remain unavailable "on-file." Making the results of studies available
      to the public is not only ethical and good scientific citizenship, but
      ultimately, also good business.

PMID- 20157349
TI  - Survival of the Fattest.

PMID- 20157350
TI  - The proper name as starting point for basic reading skills.
AB  - Does alphabetic-phonetic writing start with the proper name and how does the name
      affect reading and writing skills? Sixty 4- to 5(1/2)-year-old children from
      middle SES families with Dutch as their first language wrote their proper name
      and named letters. For each child we created unique sets of words with and
      without the child's first letter of the name to test spelling skills and phonemic
      sensitivity. Name writing correlated with children's knowledge of the first
      letter of the name and phonemic sensitivity for the sound of the first letter of
      the name. Hierarchical regression analysis makes plausible that both knowledge of
      the first letter's name and phonemic sensitivity for this letter explain why name
      writing results in phonetic spelling with the name letter. Practical implications
      of the findings are discussed.

PMID- 20157351
TI  - Determination of Sinapic Acid Derivatives in Canola Extracts Using High
      Performance Liquid Chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method with diode array
      detection (DAD) was used to determine the total phenolics, including sinapic acid
      derivatives in canola. Ten Western Canadian canola seeds, six other commodity
      canola seeds, their corresponding press cakes and meals were analyzed. Seeds of
      European 00 rapeseed and Brassica Juncea (Indian mustard) were included for
      comparison. Phenolic compounds were separated using a gradient elution system of
      water-methanol-omicron-phosphoric acid solution with a flow rate of 0.8 ml/min.
      In addition to sinapine (SP) and sinapic acid (SA), sinapoyl glucose (SG) is
      reported in the methanolic extracts. The detection and quantification limits of
      these compounds were 0.20-0.40 and 0.50-0.80 mug/ml, respectively with recovery
      values over 98.0%. The content of total phenolics, SP, SA and SG in canola
      extracts ranged from 9.16 to 16.13, 6.39 to 12.28, 0.11 to 0.59 and 1.36 to 7.50
      mg/g, respectively with significant differences among varieties.

PMID- 20157352
TI  - Genetic analysis of typical wet-type age-related macular degeneration and
      polypoidal choroidal vasculopathy in Japanese population.
AB  - Age-related macular degeneration (AMD) is a common cause of blindness in the
      elderly. Caucasian patients are predominantly affected by the dry form of AMD,
      whereas Japanese patients have predominantly the wet form of AMD and/or
      polypoidal choroidal vasculopathy (PCV). Although genetic association in the
      10q26 (ARMS2/HTRA1) region has been established in many ethnic groups for dry
      type AMD, typical wet-type AMD, and PCV, the contribution of the 1q32 (CFH)
      region seem to differ among these groups. Here we show a single nucleotide
      polymorphism (SNP) in the ARMS2/HTRA1 locus is associated in the whole genome for
      Japanese typical wet-type AMD (rs10490924: p = 4.1 x 10(-4), OR = 4.16) and PCV
      (rs10490924: p = 3.7 x 10(-8), OR = 2.72) followed by CFH (rs800292: p = 7.4 x
      10(-5), OR = 2.08; p = 2.6 x 10(-4), OR = 2.00), which differs from previous
      studies in Caucasian populations. Moreover, a SNP (rs2241394) in complement
      component C3 gene showed significant association with PCV (p = 2.5 x 10(-3), OR =
      3.47). We conclude that dry-type AMD, typical wet-type AMD, and PCV have both
      common and distinct genetic risks that become apparent when comparing Japanese
      versus Caucasian populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s12177-009-9047-1) contains supplementary
      material, which is available to authorized users.

PMID- 20157354
TI  - Use of bioanalyzer electropherograms for quality control and target evaluation in
      microarray expression profiling studies of ocular tissues.
AB  - Expression profiling with DNA microarrays has been used to examine the
      transcriptome of a wide spectrum of vertebrate cells and tissues. The sensitivity
      and accuracy of the data generated is dependent on the quality and composition of
      the input RNA. In this report, we examine the quality and array performance of
      over 200 total RNA samples extracted from ocular tissues and cells that have been
      processed in a microarray core laboratory over a 7-year period. Total RNA
      integrity and cRNA target size distribution were assessed using the 2100
      Bioanalyzer. We present Affymetrix GeneChip array performance metrics for
      different ocular samples processed according to a standard microarray assay
      workflow including several quality control checkpoints. Our review of ocular
      sample performance in the microarray assay demonstrates the value of considering
      tissue-specific characteristics in evaluating array data. Specifically, we show
      that Bioanalyzer electropherograms reveal highly abundant mRNAs in lacrimal gland
      targets that are correlated with variation in array assay performance. Our
      results provide useful benchmarks for other gene expression studies of ocular
      systems.

PMID- 20157355
TI  - Transcriptomic comparison of the retina in two mouse models of diabetes.
AB  - Mouse models of type I diabetes offer the potential to combine genetic approaches
      with other pharmacological or physiological manipulations to investigate the
      pathophysiology and treatment of diabetic retinopathy. Type I diabetes is induced
      in mice through chemical toxins or can arise spontaneously from genetic
      mutations. Both models are associated with retinal vascular and neuronal changes.
      Retinal transcriptomic responses in C57BL/6J mice treated with streptozotocin and
      Ins2(Akita/+) were compared after 3 months of hyperglycemia. Specific gene
      expression changes suggest a neurovascular inflammatory response in diabetic
      retinopathy. Genes common to the two models may represent the response of the
      retina to hyperglycemia, while changes unique to each model may represent time
      dependent disease progression differences in the various models. Further
      investigation of the commonalities and differences between mouse models of type I
      diabetes may define cause and effect events in early diabetic retinopathy disease
      progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s12177-009-9045-3) contains supplementary material, which is
      available to authorized users.

PMID- 20157353
TI  - The role of DNA microarrays in Toxoplasma gondii research, the causative agent of
      ocular toxoplasmosis.
AB  - Ocular toxoplasmosis, which is caused by the protozoan parasite Toxoplasma
      gondii, is the leading cause of retinochoroiditis. Toxoplasma is an obligate
      intracellular pathogen that replicates within a parasitophorous vacuole.
      Infections are initiated by digestion of parasites deposited in cat feces or in
      undercooked meat. Parasites then disseminate to target tissues that include the
      retina where they then develop into long-lived asymptomatic tissue cysts.
      Occasionally, cysts reactivate and growth of newly emerged parasites must be
      controlled by the host's immune system or disease will occur. The mechanisms by
      which Toxoplasma grows within its host cell, encysts, and interacts with the
      host's immune system are important questions. Here, we will discuss how the use
      of DNA microarrays in transcriptional profiling, genotyping, and epigenetic
      experiments has impacted our understanding of these processes. Finally, we will
      discuss how these advances relate to ocular toxoplasmosis and how future research
      on ocular toxoplasmosis can benefit from DNA microarrays.

PMID- 20157356
TI  - Bioinformatics and the eye.

PMID- 20157357
TI  - Techniques for accurate protein identification in shotgun proteomic studies of
      human, mouse, bovine, and chicken lenses.
AB  - Analysis of shotgun proteomics datasets requires techniques to distinguish
      correct peptide identifications from incorrect identifications, such as linear
      discriminant functions and target/decoy protein databases. We report an
      efficient, flexible proteomic analysis workflow pipeline that implements these
      techniques to control both peptide and protein false discovery rates. We
      demonstrate its performance by analyzing two-dimensional liquid chromatography
      separations of lens proteins from human, mouse, bovine, and chicken lenses. We
      compared the use of International Protein Index databases to UniProt databases
      and no-enzyme SEQUEST searches to tryptic searches. Sequences present in the
      International Protein Index databases allowed detection of several novel
      crystallins. An alternate start codon isoform of betaA4 was found in human lens.
      The minor crystallin gammaN was detected for the first time in bovine and chicken
      lenses. Chicken gammaS was identified and is the first member of the gamma
      crystallin family observed in avian lenses. ELECTRONIC SUPPLEMENTARY MATERIAL:
      The online version of this article (doi:10.1007/s12177-009-9042-6) contains
      supplementary material, which is available to authorized users.

PMID- 20157358
TI  - Metabolomic analysis of human disease and its application to the eye.
AB  - Metabolomics, the analysis of the metabolite profile in body fluids or tissues,
      is being applied to the analysis of a number of different diseases as well as
      being used in following responses to therapy. While genomics involves the study
      of gene expression and proteomics the expression of proteins, metabolomics
      investigates the consequences of the activity of these genes and proteins. There
      is good reason to think that metabolomics will find particular utility in the
      investigation of inflammation, given the multi-layered responses to infection and
      damage that are seen. This may be particularly relevant to eye disease, which may
      have tissue specific and systemic components. Metabolomic analysis can inform us
      about ocular or other body fluids and can therefore provide new information on
      pathways and processes involved in these responses. In this review, we explore
      the metabolic consequences of disease, in particular ocular conditions, and why
      the data may be usefully and uniquely assessed using the multiplexed analysis
      inherent in the metabolomic approach.

PMID- 20157360
TI  - Educational Priorities for Children with Cri-Du-Chat Syndrome.
AB  - There are few data on the educational needs of children with cri-du-chat
      syndrome: a neurodevelopmental disorder that affects learning and development. We
      therefore designed an Internet survey to identify parents' educational priorities
      in relation to children's level of need/ability. The survey listed 54
      skills/behaviors (e.g., toileting, expresses wants and needs, and tantrums)
      representing 10 adaptive behavior domains (e.g., self-care, communication, and
      problem behavior). Parents rated their child's current level of
      ability/performance with respect to each skill/behavior and indicated the extent
      to which training/treatment was a priority. Fifty-four surveys were completed
      during the 3-month data collection period. Parents identified nine high priority
      skills/behaviors. Results supported the view that parent priorities are often
      based on the child's deficits and emergent skills, rather than on child
      strengths. Implications for educational practice include the need for competence
      to develop high priority skills/behaviors and the value of assessing children's
      deficits and emergent skills to inform the content of individualized education
      plans.

PMID- 20157359
TI  - Differential gene expression in the developing human macula: microarray analysis
      using rare tissue samples.
AB  - The macula is a unique and important region in the primate retina that achieves
      high resolution and color vision in the central visual field. We recently
      reported data obtained from microarray analysis of gene expression in the macula
      of the human fetal retina (Kozulin et al., Mol Vis 15:45-59, 1). In this paper,
      we describe the preliminary analyses undertaken to visualize differences and
      verify comparability of the replicates used in that study, report the
      differential expression of other gene families obtained from the analysis, and
      show the reproducibility of our findings in several gene families by quantitative
      real-time PCR.

PMID- 20157361
TI  - Low Motor Assessment: A Comparative Pilot Study with Young Children With and
      Without Motor Impairment.
AB  - Most of the developmental instruments that measure cognitive development in
      children rely heavily on fine motor skills, especially for young children whose
      language skills are not yet well developed. This is problematic when evaluating
      the cognitive development of young children with motor impairment. The purpose of
      this study is to assess the need for a Low Motor adapation of a standardized
      instrument when testing children with motor impairment. To accomplish this, we
      have adapted the procedures, item instructions and play material of a widely used
      and standardized instrument, the Bayley Scales of Infant Development-Second
      Edition (BSID-II, Bayley 1993). The Original and the Low Motor versions were
      administered to 20 children experiencing typical development and 19 children with
      motor impairment within a period of two weeks. Results showed that children with
      motor impairments scored significantly higher on the Low Motor version of the
      Bayley Mental Scale than on the Original version: a difference of between 5 and
      10 points when the score is expressed in terms of a developmental index score.
      Results from children with typical development support the assumption that item
      content and difficulty remain unchanged in the Low Motor version.

PMID- 20157362
TI  - A Comparison of Cardiovascular Biomarkers in Patients Treated for Three Months
      with Etoricoxib, Celecoxib, Ibuprofen, and Placebo.
AB  - OBJECTIVES: Selective cyclooxygenase (COX)-2 inhibitors are effective analgesic
      and anti-inflammatory agents with improved gastrointestinal safety and
      tolerability compared with traditional NSAIDs. However, data from long-term,
      placebo-controlled studies have shown an increased risk of thrombotic
      cardiovascular (CV) events for COX-2 inhibitors. Changes in levels of CV
      biomarkers are potentially useful surrogate measures of pathologic changes
      associated with CV risk. METHODS: We randomized 433 patients with osteoarthritis
      to etoricoxib 90 mg once daily, celecoxib 200 mg twice daily, ibuprofen 800 mg
      three times daily, or placebo for 12 weeks. The hypothesis was that etoricoxib
      would be non-inferior or superior to placebo in effect on C-reactive protein
      (CRP), LDL-cholesterol, homocysteine, and fibrinogen. RESULTS: Relative to
      placebo, etoricoxib was noninferior for effect on CRP (decreased 7.8% vs.
      placebo; 97.5% CI of the difference: -30.5, 22.4), LDL-C (-4.0% vs. placebo;
      97.5% CI: -10.6, 3.2), homocysteine (-3.9% vs. placebo; 97.5% CI: -11.6, 4.6),
      and fibrinogen (-3.7% vs. placebo; 97.5% CI: -9.4, 2.3). Etoricoxib was not
      different from placebo, celecoxib, or ibuprofen for any biomarker. CONCLUSION:
      Etoricoxib was comparable to placebo, celecoxib, and ibuprofen for effects on the
      CV risk markers measured.

PMID- 20157363
TI  - Left Ventricular Diastolic Function in Nigerian Patients with Essential
      Hypertension: A Retrospective Study to Compare Angiotensin Converting Enzyme
      Inhibitors, Calcium Channel Blockade or Their Combination.
AB  - BACKGROUND: Hypertension in blacks imposes a greater left ventricular
      hypertrophy, and accelerated heart failure onset. We evaluated and compared the
      echocardiographically determined systolic and left ventricular diastolic
      functional indices in Nigerian hypertensive patients, associated with the chronic
      use of ACE inhibitors, Calcium channel blockers (CCB) or their combinations.
      METHODS: Ejection fraction -EF, intraventricular relaxation time (IVRT), E/A peak
      velocity ratio, E wave deceleration time] as well as the left ventricular mass
      index (LVMI) was undertaken among 41 Nigerian patients with essential
      hypertension only, on treatment for 4-6 months prior. The 41 patients (aged 59 +/
      10 years, 40% females) were divided into three groups; those receiving (i) ACE
      inhibitors; or (ii) CCB or (iii) combination of ACEI and CCB. All the three
      groups had a background of diuretic treatment for optimal blood pressure control.
      RESULTS: There were no statistically significant differences in the mean LVMI or
      sitting blood pressure between treatment groups. E/A ratio for ACEI treatment was
      1.06 +/- 0.44, CCB 0.74 +/- 0.19, and for ACEI + CCB 0.87 +/- 0.26 (F = 3.29, P =
      0.048 anova). The 95% confidence interval for the E/A ratio on ACEI was 0.8 to
      1.33. The A wave duration time integral (AVVTi) were all abnormally large, but
      showed a significant between treatment group difference (P = 0.037, anova). The
      values were 21.9 +/- 4.7 for ACEI, 25.3 +/- 6.3 for CCB, and least at 20.1 +/-
      3.6 cm for the ACE + CCB combination. Similarly, the IVRT was lowest and <100 ms
      with ACEI + CCB being 93 +/- 18 ms, ACEI 115 +/- 23 ms, and CCB being 117 +/- 22
      ms (F = 4.92, P = 0.01, anova). The 95% CI for IVRT on ACEI + CCB was 82 to 104
      ms. There were no between treatment group differences in systolic contractility,
      (fractional shortening or EF). CONCLUSIONS: The results indicate that use of an
      antihypertensive drug regime inclusive of an ACE inhibitor (+/-CCB) may be
      associated with greater salutary effect on indices of diastolic function, (E/A >
      1, lower AVVTi, IVRT < 100 ms) even in the presence of an equivalent effect on
      systolic function and blood pressure.

PMID- 20157364
TI  - Effects of C-reactive Protein and Homocysteine on Cytokine Production: Modulation
      by Pravastatin.
AB  - OBJECTIVE: C-reactive protein (CRP) and homocysteine are markers of
      cardiovascular risk that may have inflammatory effects. HMG coenzyme A reductase
      inhibitors (statins) have anti-inflammatory effects in vitro, but it is not clear
      if such responses in vivo are secondary to lipid lowering. We examined the
      hypothesis that CRP and homocysteine would stimulate cytokine release in human
      whole blood and that short-term treatment with a statin would inhibit it.
      METHODS: The time course of IL-6 and MCP-1 production was determined in whole
      blood incubated with saline, 1 microg/mL lipopolysaccaride (LPS), 50 and 100
      microM/L DL-homocysteine, and 5 microg/mL human recombinant CRP for 24 hours at
      37 degrees C under 5% CO(2) atmosphere. Cytokine responses were determined in
      blood drawn from 15 healthy volunteers before and after administration of
      pravastatin 40 mg daily for 2 days. RESULTS: Both human recombinant CRP and LPS
      significantly increased the production of IL-6 and MCP-1 in whole blood samples
      more than 4-fold (P < 0.001) but homocysteine did not. Oral administration of
      pravastatin, 40mg daily for 2 days, decreased CRP-stimulated IL-6 production by
      approximately 20% (P = 0.02) 6 hours after incubation, but did not affect MCP-1
      production (P = 0.69). Pravastatin treatment did not affect LPS-stimulated MCP-1
      but increased IL-6 modestly. CONCLUSIONS: CRP stimulated the production of the
      proatherogenic mediators MCP-1 and IL-6 in human whole blood, but homocysteine
      did not. CRP-stimulated production of IL-6, but not MCP-1, was modestly
      attenuated by short-term treatment with pravastatin.

PMID- 20157365
TI  - Drugs to Treat Systemic Lupus Erythematosus: Relationship between Current Use and
      Cardiovascular Risk Factors.
AB  - OBJECTIVES: Cardiovascular risk is increased in patients with systemic lupus
      erythematosus (SLE). Drugs used to treat SLE can modify traditional
      cardiovascular risk factors. We examined the effect of selected drugs used in the
      treatment of SLE on cardiovascular risk factors. METHODS: We compared systolic
      and diastolic blood pressure, serum lipid concentrations, glucose, homocysteine,
      and urinary F(2)-isoprostane concentrations in 99 patients with lupus who were
      either current users or non-users of systemic corticosteroids, antimalarials, non
      steroidal anti-inflammatory drugs (NSAIDs), COX-2 selective NSAIDs, azathioprine,
      and methotrexate. Multivariable adjustment was done with linear regression
      modeling using sex, age and disease activity (SLEDAI) as controlling variables.
      RESULTS: Serum triglyceride concentrations were higher (135.1 +/- 61.4 vs. 95.3
      +/- 47.5 mg/dL, adjusted P = 0.003) in patients receiving corticosteroids.
      Homocysteine concentrations were marginally higher in patients receiving
      methotrexate (adjusted P = 0.08). Current use of either NSAIDs or COX-2
      inhibitors was not associated with increased cardiovascular risk factors. Current
      hydroxychloroquine use was not associated with significant alterations in lipid
      profiles. CONCLUSIONS: In a non-random sample of patients with SLE, current
      corticosteroid use was associated with increased triglyceride concentrations, but
      other drugs had little effect on traditional cardiovascular risk factors.

PMID- 20157366
TI  - Probiotic Pre-treatment Reduces Gliclazide Permeation (ex vivo) in Healthy Rats
      but Increases It in Diabetic Rats to the Level Seen in Untreated Healthy Rats.
AB  - AIM: To investigate the influence of probiotic pre-treatment on the permeation of
      the antidiabetic drug gliclazide in healthy and diabetic rats. METHODS: Wistar
      rats (age 2-3 months, weight 350 +/- 50 g) were randomly allocated into one of 4
      groups (N = 16 each group): healthy control, healthy probiotic, diabetic control,
      and diabetic probiotic. Probiotics (75 mg/kg, equal quantities of Lactobacillus
      acidophilus, Bifidobacterium lactis, and Lactobacillus rhamnosus) were
      administered twice a day for three days to the appropriate groups after diabetes
      had been induced with alloxan i.v. 30 mg/kg. Rats were sacrificed, ileal tissues
      mounted in Ussing chambers and gliclazide (200 microg/mL) was administered for
      the measurement of the mucosal to serosal absorption Jss((MtoS)) and serosal to
      mucosal secretion Jss((StoM)) of gliclazide. RESULTS: Treatment of healthy rats
      with probiotics reduced Jss((MtoS)) of gliclazide from 1.2 +/- 0.3 to 0.3 +/- 0.1
      microg/min/cm(2) (P < 0.01) and increased Jss((StoM))from 0.6 +/- 0.1 to 1.4 +/-
      0.3 (P < 0.01) resulting in net secretion while, in diabetic tissues, treatment
      with probiotics increased both Jss((MtoS)) and Jss((StoM))fluxes of gliclazide to
      the comparable levels of healthy tissues resulting in net absorption. DISCUSSION:
      In healthy rats, the reduction in Jss((MtoS)) after probiotics administration
      could be explained by the production of bacterial metabolites that upregulate the
      mucosal efflux drug transporters Mrp2 that control gliclazide transport. In
      diabetic rats, the restored fluxes of gliclazide after probiotic treatment,
      suggests the normalization of the functionality of the drug transporters
      resulting in a net absorption. CONCLUSION: Probiotics may alter gliclazide
      transport across rat ileal tissue studied ex vivo.

PMID- 20157367
TI  - Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to
      Respond.
AB  - In the past four decades, chemoprevention of colorectal cancer (CRC) has been the
      subject of many epidemiologic and intervention trials of naturally occurring or
      pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as
      a viable option in this context was a major breakthrough; however, it was
      hampered by adverse cardiovascular events. This review questions whether
      chemopreventive measures for CRC are ready to be used in mass or individual
      applications, standing alone or in combination with other CRC-preventive
      measures. It also discusses steps that may be undertaken to explore this field
      further.

PMID- 20157368
TI  - Secondary Prevention of Colorectal Cancer: Is There an Optimal Follow-up for
      Patients with Colorectal Cancer?
AB  - Secondary prevention of colorectal cancer, as opposed to primary prevention,
      indicates that a person has already had the disease and there are steps being
      taken to prevent cancer recurrence, usually as metachronous tumors. This
      generally involves annual surveillance with colonoscopy after surgical removal of
      the initial cancer if some aspect of the colon remains. However, some familial
      cases may involve other modalities, such as cyclooxygenase inhibitors, as an
      adjunct after the initial operation. Genetic testing in suspected familial cases
      may identify candidates for secondary prevention. The timing for secondary
      prevention is critical to prevent recurrent advanced disease, which is
      detrimental to patient survival. Recommendations are often empiric, but some
      cases are based on the biological behavior of the tumor. Close follow-up with a
      competent health care provider, such as a gastroenterologist, is necessary to
      help prevent recurrence.

PMID- 20157369
TI  - Alu-element insertion in an OPA1 intron sequence associated with autosomal
      dominant optic atrophy.
AB  - PURPOSE: Autosomal dominant optic atrophy (ADOA) is the most common form of
      hereditary optic neuropathy caused by mutations in the optic atrophy 1 (OPA1)
      gene. It is characterized by insidious onset with a selective degeneration of
      retinal ganglion cells, variable loss of visual acuity, temporal optic nerve
      pallor, tritanopia, and development of central, paracentral, or cecocentral
      scotomas. Here we describe the clinical and molecular findings in a large Italian
      family with ADOA. METHODS: Routine ophthalmologic examination and direct
      sequencing of all coding regions of the OPA1 gene were performed. Further
      characterization of a new OPA1 gene insertion was performed by reverse
      transcription-PCR (RT-PCR) of RNA from patients and control subjects. RESULTS: We
      identified an Alu-element insertion located in intron 7 of OPA1 causing an in
      frame deletion of exon 8 in 18 family members. CONCLUSIONS: The predicted
      consequence of this mutation is the loss of the guanosine triphosphatase (GTPase)
      activity of OPA1. Alu insertions have been reported in the literature as causing
      human genetic disease. However, this is the first report of a pathogenic OPA1
      gene mutation resulting from an Alu insertion.

PMID- 20157370
TI  - The role of computed tomography in the presurgical diagnosis of foraminal
      entrapment of lumbosacral junction.
AB  - OBJECTIVE: On the basis of preoperative computed tomography (CT) scans, we
      studied the change of the size of anterior primary division (APD) of the L5
      spinal root in the presence of foraminal/extraforaminal entrapment of the L5
      spinal root. METHODS: Two independent radiologists retrospectively reviewed the
      preoperative CT scans of 27 patients treated surgically and compared the sizes of
      the APDs on bilateral L5 spinal roots. If one side APD size was larger than the
      other side APD size, it was described as left or right "dominancy" and regarded
      this as "consensus (C)" in case that there was a consensus between the larger APD
      and the location of sciatica, and regarded as "non-consensus (NC)" in case that
      there was not a consensus. Oswestry Disability Index (ODI) scores were used for
      preoperative and postoperative evaluation. RESULTS: On CT scans, twenty-one (77%)
      of 27 patients were the consensus group (APD swelling) and 6 (22%) were a non
      consensus group (APD no swelling). In 9 patients with acute foraminal disc
      herniations, asymmetric enlargement of the APD on L5 spinal root was detected in
      all cases (100%) and detected in 11 (64%) of 17 patients with stenosis.
      Preoperative ODI score was 75-93 (mean 83) and postoperative ODI scores were
      improved to 13-36 (mean 21). The mean follow-up period was 6 months (range, 3-11
      months). CONCLUSION: An asymmetric enlargement of the APD on L5 spinal root on CT
      scans is meaningfully associated with a foraminal or extraforaminal entrapment of
      the L5 spinal root on the lumbosacral junction.

PMID- 20157371
TI  - Intracranial pressure and experimental model of diffuse brain injury in rats.
AB  - OBJECTIVE: In this study, we present a simple closed head injury model as a two
      stage experiment. The height of the weight drop enables gradation of head trauma
      severity. METHODS: The head injury device consists of three parts and there are
      three adjustable parameters-weight (100-600 g), height of fall (5-100 cm) and
      elasticity of the springs. Thirty male Wistar rats underwent monitoring of
      intracranial pressure with and without induction of the head injury. RESULTS: The
      weight drop from 45 to 100 cm led to immediate seizure activity and early death
      of the experimental animals. Severe head injury was induced from 40 cm weight
      drop. There was 50% mortality and all surviving rats had behavioral
      deterioration. Intracranial pressure was 9.3 +/- 3.76 mmHg. Moderate head injury
      was induced from 35 cm, mortality decreased to 20-40%, only half of the animals
      showed behavioral pathology and intracranial pressure was 7.6 +/- 3.54 mmHg.
      Weight drop from 30 cm caused mild head injury without mortality and neurological
      deterioration. Intracranial pressure was slightly higher compared to sham group-
      5.5 +/- 0.74 mmHg and 2.9 +/- 0.81 mmHg respectively. CONCLUSION: This model is
      an eligible tool to create graded brain injury with stepwise intracranial
      pressure elevation.

PMID- 20157372
TI  - Possible role of matrix metalloproteinase in osteolytic intracranial meningiomas.
AB  - OBJECTIVE: Abnormalities of the bone are frequently encountered in patients with
      meningioma, and hyperostosis and endostosis are common bone alterations in these
      tumors. Extensive bony destruction is very unusual in patients with meningioma.
      We report six cases of intracranial meningioma associated with an osteolytic
      lesion of the skull and discuss the underlying mechanisms that may be responsible
      for bone destruction in patients with meningioma. METHODS: Six patients were
      classified into three groups, severe, moderate and mild, according to the degree
      of osteolytic bony destruction. The tumor was classified as intracranial or
      extracranial, depending on its location. We investigated the potential role of
      matrix metalloproteinase (MMP) in meningioma-associated osteolysis. The levels of
      MMP expression were determined by gelatin zymography, reverse transcription
      quantitative PCR analysis (RT-PCR) and immunohistochemical analysis. RESULTS:
      Complete surgical removal of the lesion was performed in each patient.
      Histological examination revealed benign meningioma in four cases, and two cases
      of atypical meningioma. Patients did not have a poor prognosis except one case of
      recurred atypical meningioma. Gelatin zymography and RT-PCR detected high levels
      of MMP-2 in almost all extracranial masses in comparison with the intracranial
      masses and MMP-9 in two. There was no difference in the severity of bone
      destruction. Immunohistochemical analysis revealed MMP-2 expression in the
      vicinity of the bone destruction, and a few MMP-9-positive stainings were
      observed. CONCLUSION: Osteolysis of the skull in patients with meningiomas might
      not be indicative of malignant pathological features and poor prognosis. Invasion
      to the extracranial portion and osteolysis might be associated with MMP-2
      expression in meningioma.

PMID- 20157373
TI  - Functional reorganization associated with semantic language processing in
      temporal lobe epilepsy patients after anterior temporal lobectomy : a
      longitudinal functional magnetic resonance image study.
AB  - OBJECTIVE: The focus of this study is brain plasticity associated with semantic
      aspects of language function in patients with medial temporal lobe epilepsy
      (mTLE). METHODS: Using longitudinal functional magnetic resonance imaging (fMRI),
      patterns of brain activation were observed in twelve left and seven right
      unilateral mTLE patients during a word-generation task relative to a pseudo-word
      reading task before and after anterior temporal section surgery. RESULTS: No
      differences were observed in precentral activations in patients relative to
      normal controls (n = 12), and surgery did not alter the phonological-associated
      activations. The two mTLE patient groups showed left inferior prefrontal
      activations associated with semantic processing (word-generation > pseudo-word
      reading), as did control subjects. The amount of semantic-associated activation
      in the left inferior prefrontal region was negatively correlated with epilepsy
      duration in both patient groups. Following temporal resection, semantic-specific
      activations in inferior prefrontal region became more bilateral in left mTLE
      patients, but more left-lateralized in right mTLE patients. The longer the
      duration of epilepsy in the patients, the larger the increase in the left
      inferior prefrontal semantic-associated activation after surgery in both patient
      groups. Semantic activation of the intact hippocampus, which had been negatively
      correlated with seizure frequency, normalized after the epileptic side was
      removed. CONCLUSION: These results indicate alternation of semantic language
      network related to recruitment of left inferior prefrontal cortex and functional
      recovery of the hippocampus contralateral to the epileptogenic side, suggesting
      an intra- and inter-hemispheric reorganization following surgery.

PMID- 20157374
TI  - Different Expression of Extracellular Matrix Genes : Primary vs. Recurrent Disc
      Herniation.
AB  - OBJECTIVE: Recurrent lumbar disc herniation has been reported to occur in 5% to
      15% of surgically treated primary lumbar disc herniation cases. We investigated
      the molecular biologic characteristics of primary herniated discs and recurrent
      discs to see whether the recurrent discs has the similar biological features with
      primary herniated discs. METHODS: Primary herniated disc and recurrent disc cells
      were obtained by discectomy of lumbar disc patients and cells were isolated and
      then taken through monolayer cultures. We compared chondrogenic and osteogenic
      mRNA gene expression, and western blot between the two groups. RESULTS: The mRNA
      gene expression of recurrent disc cells were increased 1.47* times for aggrecan,
      1.38 times for type I collagen, 2.04 times for type II collagen, 1.22 times for
      both Sox-9 and osteocalcin, and 1.31 times for alkaline phosphatase,
      respectively, compared with the primary herniated lumbar disc cells (*indicates p
      < 0.05). Western blot results for each aggrecan, type I collagen, type II
      collagen, Sox-9, osteocalcin, and alkaline phosphatase were similar between the
      primary herniated disc cells and recurrent disc cells. CONCLUSION: These results
      indicate that the recurrent disc cells have similar chondrogenic and osteogenic
      gene expression compared to primary herniated disc cells. Therefore, we assumed
      that the regeneration of remaining discs could fill the previous discectomy space
      and also it could be one of the factors for disc recurrence especially in the
      molecular biologic field.

PMID- 20157375
TI  - The Effects of TWEAK, Fn14, and TGF-beta1 on Degeneration of Human Intervertebral
      Disc.
AB  - OBJECTIVE: The purpose of this study is to explain the effect and reciprocal
      action among tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK),
      fibroblast growth factor-inducible 14 (Fn14), and transforming growth factor
      beta1 (TGF-beta1) on degeneration of human intervertebral disc (IVD). METHODS:
      Human intervertebral disc tissues and cells were cultured with Dulbecco's
      Modified Eagle's Medium/Nutrient F-12 Ham (DMEM/F-12) media in 37, 5% CO(2)
      incubator. When IVD tissues were cultured with TWEAK, Fn14 that is an
      antagonistic receptor for TWEAK and TGF-beta1, the level of sulfated
      glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay and
      sex determining region Y (SRY)-box 9 (Sox9) and versican messenger ribonucleic
      acid (mRNA) levels were estimated by reverse transcriptase polymerase chain
      reaction (RT-PCR). RESULTS: When human IVD tissue was cultured for nine days, the
      sGAG content was elevated in proportion to culture duration. The sGAG was
      decreased significantly by TWEAK 100 ng/mL, however, Fn14 500 ng/mL did not
      change the sGAG production of IVD tissue. The Fn14 increased versican and Sox9
      mRNA levels decreased with TWEAK in IVD tissue TGF-beta1 20 ng/mL elevated the
      sGAG concentration 40% more than control. The sGAG amount decreased with TWEAK
      was increased with Fn14 or TGF-beta1 but the result was insignificant
      statistically. TGF-beta1 increased the Sox9 mRNA expression to 180% compared to
      control group in IVD tissue. Sox9 and versican mRNA levels decreased by TWEAK
      were increased with TGF-beta1 in primary cultured IVD cells, however, Fn14 did
      not show increasing effect on Sox9 and versican. CONCLUSION: This study suggests
      that TWEAK would act a role in intervertebral disc degeneration through
      decreasing sGAG and the mRNA level of versican and Sox9.

PMID- 20157376
TI  - Morphological characteristics of the thalamoperforating arteries.
AB  - OBJECTIVE: The aim of this study was to investigate the morphological
      characteristics of the thalamoperforating arteries that arise from the P1 segment
      of the posterior cerebral artery. METHODS: Thalamoperforating arteries located in
      the interpeduncular fossa were dissected in 26 formalin-fixed human cadaver
      brains. We investigated the origin site of thalamoperforating arteries from the
      P1 segment, number and diameter, and variations in their origin. RESULTS:
      Thalamoperforating arteries arose from the superior, posterior or posterosuperior
      surfaces of the P1 segment at the mean 1.93 mm (range, 0.41-4.71 mm) distance
      from the basilar apex and entered the brain through the posterior perforated
      substance. The average number was 3.6 (range 1-8) and mean diameter was 0.70 mm
      (range 0.24-1.18 mm). Thalamoperforating arteries could be classified into five
      different types according to their origin at the P1 segment : Type I (bilateral
      multiple), 38.5%; Type II (unilateral single, unilateral multiple), 26.9%; Type
      III (bilateral single), 19.2%; Type IV (unilateral single), 11.5%; Type V
      (unilateral multiple), 3.8%. In 15.4% of all specimens, thalamoperforating
      arteries arose from the only one side of P1 segment and were not noted in the
      other side. In such cases, the branches arising from the one side of P1 segment
      supplied the opposite side. CONCLUSION: Variations in the origin of the
      thalamoperforating arteries should be keep in mind to perform the surgical
      clipping, endovascular treatment or operation involving the interpeduncular
      fossa. In particular, unilateral single branch seems to be very risky and
      significant for surgical technique or endovascular treatment.

PMID- 20157377
TI  - Morphometric study of the korean adult pituitary glands and the diaphragma
      sellae.
AB  - OBJECTIVE: To investigate the morphometric characteristics of the pituitary gland
      and diaphragma sellae in Korean adults. METHODS: Using the 33 formaline fixed
      adult cadavers (23 male, 10 female), the measurements were taken at the
      diaphragma sellae and pituitary gland. The authors investigated the relationship
      between dura and structures surrounding pituitary gland, morphometric aspects of
      pituitary gland and stalk, and morphometric aspect of central opening of
      diaphragma sellae. RESULTS: The boundary between the lateral surface of pituitary
      gland and the medial wall of cavernous sinus was formed by the thin dural layer
      and pituitary capsule. The pituitary capsule adherent tightly to the pituitary
      gland was observed to continue from the diaphragma sellae. Mean width, length,
      and height of the pituitary gland were 14.3 +/- 2.1, 7.9 +/- 1.3, and 6.0 +/- 0.9
      mm in anterior lobes, and 8.7 +/- 1.7, 2.9 +/- 1.1, and 5.8 +/- 1.0 mm in
      posterior lobes, respectively. Although all dimensions of anterior lobe in female
      were slightly larger than those in male, statistical significance was noted in
      only longitudinal dimension. The ratio of posterior lobe to the whole length of
      pituitary gland was about 27%. The mean thickness of pituitary stalk was 2 mm.
      The diaphragmal opening was 5 mm or more in 26 (78.8%) of 33 specimen. The
      opening was round in 60.6% of the specimen, and elliptical oriented in an
      anterior-posterior or transverse direction in 39.4%. CONCLUSION: These results
      provide the safe anatomical knowledge during the transsphenoidal surgery and may
      be helpful to access the possibility of the development of empty sella syndrome.

PMID- 20157378
TI  - Spontaneous intracranial hypotension secondary to lumbar disc herniation.
AB  - Spontaneous intracranial hypotension is often idiopathic. We report on a patient
      presenting with symptomatic intracranial hypotension and pain radiating to the
      right leg caused by a transdural lumbar disc herniation. Magnetic resonance (MR)
      imaging of the brain revealed classic signs of intracranial hypotension, and an
      additional spinal MR confirmed a lumbar transdural herniated disc as the cause.
      The patient was treated with a partial hemilaminectomy and discectomy. We were
      able to find the source of cerebrospinal fluid leak, and packed it with epidural
      glue and gelfoam. Postoperatively, the patient's headache and log radiating pain
      resolved and there was no neurological deficit. Thus, in this case, lumbar disc
      herniation may have been a cause of spontaneous intracranial hypotension.

PMID- 20157379
TI  - The early detection of recurrence of malignant peripheral nerve sheath tumor by
      frequent magnetic resonance imaging.
AB  - Surgery has a key role in the treatment of malignant peripheral nerve sheath
      tumors (MPNSTs), but the resectability of paraspinal MPNSTs is only 20%.
      Therefore, spinal MPNSTs show frequent recurrence and poor prognosis. Local
      recurrence is much more common than metastasis for MPNSTs, and surgery still has
      a key role in the treatment of local recurrence. Therefore, it is important that
      recurrence must be detected before resectability is lost. However, no evidence
      based follow-up protocol has been established for MPNST. The authors performed
      gross total resection in a 34-year-old woman presented with thoracic MPNST.
      Adjuvant radiotherapy and chemotherapy were not administered since these adjuvant
      therapies generally do not improve survival in MPNST and may cause additional
      neurovascular damage. Instead, the authors monitored the primary site every 3
      months using magnetic resonance imaging to detect local recurrence at the
      earliest opportunity. The tumor recurred locally on two occasions without overt
      symptoms at 21 and 24 months postoperatively. These recurrences were treated
      successfully by gross total removal.

PMID- 20157380
TI  - Late Occurrence of Cervicothoracic Ossification of Posterior Longitudinal
      Ligaments in a Surgically Treated Thoracic OPLL Patient.
AB  - Ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine
      is rare, even in the Far East. A 45-year-old female presented with a 4-month
      history of progressive motor weakness in the lower extremities, numbness below
      the midthoracic area, and spastic gait disturbance. Neuroradiological
      examinations revealed massive OPLLs at the T4-T6 levels with severe anterior
      compression of the spinal cord. Anterior decompressive corpectomies with bone
      grafts were performed from T4 to T6 using a trans-thoracic approach. After
      surgery, the patient made an uneventful recovery. However, eleven years after
      surgery, the patient developed recurrent lower extremity weakness and spastic
      gait disturbance. De novo OPLLs at the C6-T2 levels were responsible for the
      severe spinal cord compression on this occasion. After second surgery, paralysis
      in both legs was resolved. We present a rare case of late cervicothoracic OPLL in
      a patient surgically treated for thoracic OPLL.

PMID- 20157381
TI  - Therapeutic considerations of percutaneous sacroplasty for the sacral
      insufficiency fracture.
AB  - Sacral insufficiency fracture is a debilitating injury not easily found in
      general radiologic examinations and is rarely diagnosed, since its symptoms are
      obscure. It is known to frequently occur in patients with osteoporosis, but the
      treatment has not yet been established and various kinds of treatment methods are
      being attempted. Sacroplasty is sometimes performed by applying percutaneous
      vertebroplasty which is known to be a less invasive treatment. Since the course
      of diagnosis of sacral insufficiency fracture is difficult and clear guidelines
      for treatments have not yet been established, many spine surgeons fail to
      diagnose patients or speculate on treatment methods. We report our experience in
      diagnosing a sacral insufficiency fracture in a 54-year-old healthy female
      patient using MRI and treating her with sacroplasty. From a therapeutic point of
      view, we then cover the usefulness, effects and characteristics relating to the
      complications of sacroplasty, along with literature review.

PMID- 20157382
TI  - Mobility of intradural extramedullary schwannoma at spine : report of three cases
      with literature review.
AB  - Although very rare, a few cases of intradural extramedullary (IDEM) spinal tumor
      migration have been reported since Tomimatsu first reported a mobile schwannoma
      of the cervical cord in 1974. Schwannoma is a neurogenic tumor which originates
      from nerve sheath that it is relatively well-marginated tumor with little
      attachment or adhesion to surrounding tissue. Mobility of tumor in spinal canal
      sometimes can result in negative exploration at the expected area. We found three
      interesting cases in which different tumor locations observed in repeated
      magnetic resonance image (MRI) findings. All tumors were intradural and
      extramedullary schwannoma. We reviewed the literature about moving tumor in the
      spine through PUBMED search.

PMID- 20157383
TI  - Intracranial dissemination from spinal cord anaplastic astrocytoma.
AB  - We report a case of intracranial dissemination developing approximately 4 months
      after partial removal of a spinal cord anplastic astrocytoma in a 22-year-old
      male. He presented with paraplegia on initial admission at a local hospital.
      Spinal magnetic resonance (MR) images disclosed multiple intramedullary lesions
      at the T3-11. The tumor was partially removed. The final histologic diagnosis was
      anaplastic astrocytoma. Four months after the operation, he was admitted with the
      symptoms of headache and deterioration of consciousness. MR images showed
      enhanced lesions in the anterior horn of the left lateral ventricle, and septum
      pellucidum. He underwent computed tomography-guided stereotactic biopsy and
      histological appearance was consistent with anaplastic astrocytoma. The clinical
      course indicates that the tumor originated in the spinal cord and extended into
      the subarachnoid space, first the spinal canal and later intracranial.

PMID- 20157384
TI  - Infraoptic course of both anterior cerebral arteries.
AB  - A 28-year-old woman was referred to our hospital with a sudden, very severe
      headache. Brain computed tomographic angiography showed a saccular cerebral
      aneurysm at the bifurcation of the left middle cerebral artery and infraoptic
      courses of both anterior cerebral arteries. The anterior cerebral arteries were
      seen to arise from the ipsilateral internal cerebral arteries at the level of the
      origin of the ophthalmic artery, passed underneath the ipsilateral optic nerve,
      and turned upward at ventral portion of the optic chiasm.Infraoptic course of the
      proximal anterior cerebral artery is an extremely rare anomaly and is often
      associated with cerebral aneurysms. We report the clinical features, radiological
      findings, and possible genesis of this anomaly with a literature review.

PMID- 20157385
TI  - Successful treatment of a case with rhino-orbital-cerebral mucormycosis by the
      combination of neurosurgical intervention and the sequential use of amphotericin
      B and posaconazole.
AB  - Rhino-orbital-cerebral (ROC) mucormycosis is an uncommon, acute and aggressive
      fungal infection. It remains a challenging problem to clinicians despite
      aggressive debridement surgery and antifungal therapy. The authors describe a
      case of ROC mucormycosis with pericranial abscess occurring in a female patient
      with uncontrolled diabetes mellitus. The infection initially developed in the
      right-sided nasal sinus and later progressed through the paranasal sinuses with
      the invasion of the peri-orbital and frontotemporal region, due to the delayed
      diagnosis and treatment. Numerous non-septate hyphae of the zygomycetes were
      identified by a punch biopsy from the nasal cavity and by an open biopsy of the
      involved dura. The patient was treated successfully with extensive debridement of
      her necrotic skull and surrounding tissues, drainage of her pericranial abscess
      and antifungal therapy, including intravenous amphotericin B for 61 days and oral
      posaconazole for the following 26 days. She returned to a normal life and has had
      no recurrence since the end of her treatment 15 months ago.

PMID- 20157386
TI  - Erratum: estimated number of korean adults with back pain and population-based
      associated factors of back pain : data from the fourth Korea national health and
      nutrition examination survey.
AB  - [This corrects the article on p. 443 in vol. 46, PMID: 20041054.].

PMID- 20157387
TI  - Effects of TGF-beta1 Ribbon Antisense on CCl(4)-induced Liver Fibrosis.
AB  - Ribbon-type antisense oligonucleotide to TGF-beta1 (TGF-beta1 RiAS) was designed
      and tested to prevent or resolve the fibrotic changes induced by CCl4 injection.
      When Hepa1c1c7 cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1
      mRNA was effectively reduced. TGF-beta1 RiAS, mismatched RiAS, and normal saline
      were each injected to mice via tail veins. When examined for the biochemical
      effects on the liver, TGF-beta1 mRNA levels were significantly reduced only in
      the TGF-beta1 RiAS-treated group. The results of immunohistochemical studies
      showed that TGF-beta1 RiAS prevented the accumulation of collagen and alpha
      smooth muscle actin, but could not resolve established fibrosis. These results
      indicate that ribbon antisense to TGF-beta1 with efficient uptake can effectively
      prevent fibrosis of the liver.

PMID- 20157388
TI  - Ameliorating effects of sulfonylurea drugs on insulin resistance in Otsuka long
      evans Tokushima Fatty rats.
AB  - OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity
      related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea
      drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium
      (K(ATP)) channel are commercially available to treat diabetes. The present study
      compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid
      derivatives (repaglinide) in regard to their long-term effect on ameliorating
      insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking
      water from 29 weeks of age. On high glucose loading at 45 weeks of age, response
      of blood glucose recovery was the greatest in the group treated with glimepiride.
      On immunohistochemistry analysis for the Kir6.2 subunit of K(ATP) channels,
      insulin receptor beta-subunits, and glucose transporters (GLUT) type 2 and 4 in
      liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and
      gliclazide) were more effective than repaglinide in recovery from their decreased
      expressions in OLETF rats. From these results, it seems to be plausible that
      K(ATP)-channel inhibitors containing sulfonylurea moiety may be much more
      effective in reducing insulin resistance than those with benzoic acid moiety. In
      contrast to gliclazide, non-tissue selectivity of glimepiride on K(ATP) channel
      inhibition may further strengthen an amelioration of insulin sensitivity unless
      considering other side effects.

PMID- 20157389
TI  - Roles of dopaminergic d(1) and d(2) receptors in catecholamine release from the
      rat adrenal medulla.
AB  - The aim of the present study was designed to establish comparatively the
      inhibitory effects of D(1)-like and D(2)-like dopaminergic receptor agonists,
      SKF81297 and R(-)-TNPA on the release of catecholamines (CA) evoked by
      cholinergic stimulation and membrane depolarization from the isolated perfused
      model of the rat adrenal medulla. SKF81297 (30microM) and R-(-)-TNPA (30microM)
      perfused into an adrenal vein for 60 min, produced great inhibition in the CA
      secretory responses evoked by ACh (5.32x10(- 3) M), DMPP (10(-4) M), McN-A-343
      (10(-4) M), high K(+) (5.6x10(-2) M), Bay-K-8644 (10microM), and cyclopiazonic
      acid (10microM), respectively. For the release of CA evoked by ACh, high K(+),
      DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid, the following rank order of
      inhibitory potency was obtained: SKF81297>R-(-)-TNPA. However, R(+)-SCH23390, a
      selectve D(1)-like dopaminergic receptor antagonist, and S(-)-raclopride, a
      selectve D(2)-like dopaminergic receptor antagonist, enhanced the CA secretory
      responses evoked by ACh, high K(+), DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic
      acid only for 0~4 min. The rank order for the enhancement of CA release evoked by
      high K(+), McN-A-343 and cyclopiazonic acid was R(+)-SCH23390>S(-)-raclopride.
      Also, the rank order for ACh, DMPP and Bay-K-8644 was S(-)-raclopride > R(+)
      SCH23390. Taken together, these results demonstrate that both SKF81297 and R-(-)
      TNPA inhibit the CA release evoked by stimulation of cholinergic (both nicotinic
      and muscarinic) receptors and the membrane depolarization from the isolated
      perfused rat adrenal gland without affecting the basal release, respectively, but
      both R(+)-SCH23390 and S(-)-raclopride facilitate the CA release evoked by them.
      It seems likely that the inhibitory effects of SKF81297 and R-(-)-TNPA are
      mediated by the activation of D(1)-like and D(2)-like dopaminergic receptors
      located on the rat adrenomedullary chromaffin cells, respectively, whereas the
      facilitatory effects of R(+)-SCH23390 and S(-)-raclopride are mediated by the
      blockade of D(1)-like and D(2)-like dopaminergic receptors, respectively: this
      action is possibly associated with extra- and intracellular calcium mobilization.
      Based on these results, it is thought that the presence of dopaminergic D(1)
      receptors may play an important role in regulation of the rat adrenomedullary CA
      secretion, in addition to well-known dopaminergic D(2) receptors.

PMID- 20157390
TI  - Involvement of thromboxane a(2) in the modulation of pacemaker activity of
      interstitial cells of cajal of mouse intestine.
AB  - Although many studies show that thromboxane A(2) (TXA(2)) has the action of
      gastrointestinal (GI) motility using GI muscle cells and tissue, there are no
      reports on the effects of TXA(2) on interstitial cells of Cajal (ICC) that
      function as pacemaker cells in GI tract. So, we studied the modulation of
      pacemaker activities by TXA(2) in ICC with whole cell patch-clamp technique.
      Externally applied TXA(2) (5microM) produced membrane depolarization in current
      clamp mode and increased tonic inward pacemaker currents in voltage-clamp mode.
      The tonic inward currents by TXA(2) were inhibited by intracellular application
      of GDP-beta-S. The pretreatment of ICC with Ca(2+) free solution and
      thapsigargin, a Ca(2+)-ATPase inhibitor in endoplasmic reticulum, abolished the
      generation of pacemaker currents and suppressed the TXA(2)-induced tonic inward
      currents. However, chelerythrine or calphostin C, protein kinase C inhibitors,
      did not block the TXA(2)-induced effects on pacemaker currents. These results
      suggest that TXA(2) can regulate intestinal motility through the modulation of
      ICC pacemaker activities. This modulation of pacemaker activities by TXA(2) may
      occur by the activation of G protein and PKC independent pathway via extra and
      intracellular Ca(2+) modulation.

PMID- 20157391
TI  - Lysophosphatidylcholine Increases Ca Current via Activation of Protein Kinase C
      in Rabbit Portal Vein Smooth Muscle Cells.
AB  - Lysophosphatidylcholine (LPC), a metabolite of membrane phospholipids by
      phospholipase A(2), has been considered responsible for the development of
      abnormal vascular reactivity during atherosclerosis. Ca(2+) influx was shown to
      be augmented in atherosclerotic artery which might be responsible for abnormal
      vascular reactivity. However, the mechanism underlying Ca(2+) influx change in
      atherosclerotic artery remains undetermined. The purpose of the present study was
      to examine the effects of LPC on L-type Ca(2+) current (I(Ca(L))) activity and to
      elucidate the mechanism of LPC-induced change of I(Ca(L)) in rabbit portal vein
      smooth muscle cells using whole cell patch clamp. Extracellular application of
      LPC increased I(Ca(L)) through whole test potentials, and this effect was readily
      reversed by washout. Steady state voltage dependency of activation or
      inactivation properties of I(Ca(L)) was not significantly changed by LPC.
      Staurosporine (100 nM) or chelerythrine (3 microM), which is a potent inhibitor
      of PKC, significantly decreased basal I(Ca(L)), and LPC-induced increase of
      I(Ca(L)) was significantly suppressed in the presence of PKC inhibitors. On the
      other hand, application of PMA, an activator of PKC, increased basal I(Ca(L))
      significantly, and LPC-induced enhancement of I(Ca(L)) was abolished by
      pretreatment of the cells with PMA. These findings suggest that LPC increased
      I(Ca(L)) in vascular smooth muscle cells by a pathway that involves PKC, and that
      LPC-induced increase of I(Ca(L)) might be, at least in part, responsible for
      increased Ca(2+) influx in atherosclerotic artery.

PMID- 20157392
TI  - Melatonin Induces Akt Phosphorylation through Melatonin Receptor- and PI3K
      Dependent Pathways in Primary Astrocytes.
AB  - Melatonin has been reported to protect neurons from a variety of neurotoxicity.
      However, the underlying mechanism by which melatonin exerts its neuroprotective
      property has not yet been clearly understood. We previously demonstrated that
      melatonin protected kainic acid-induced neuronal cell death in mouse hippocampus,
      accompanied by sustained activation of Akt, a critical mediator of neuronal
      survival. To further elucidate the neuroprotective action of melatonin, we
      examined in the present study the causal mechanism how Akt signaling pathway is
      regulated by melatonin in a rat primary astrocyte culture model. Melatonin
      resulted in increased astrocytic Akt phosphorylation, which was significantly
      decreased with wortmannin, a specific inhibitor of PI3K, suggesting that
      activation of Akt by melatonin is mediated through the PI3K-Akt signaling
      pathway. Furthermore, increased Akt activation was also significantly decreased
      with luzindole, a non-selective melatonin receptor antagonist. As downstream
      signaling pathway of Akt activation, increased levels of CREB phoshorylation and
      GDNF expression were observed, which were also attenuated with wortmannin and
      luzindole. These results strongly suggest that melatonin exerts its
      neuroprotective property in astrocytes through the activation of plasma membrane
      receptors and then PI3K-Akt signaling pathway.

PMID- 20157393
TI  - Effects of Apigenin on Glutamate-induced [Ca](i) Increases in Cultured Rat
      Hippocampal Neurons.
AB  - Flavonoids have been shown to affect calcium signaling in neurons. However, there
      are no reports on the effect of apigenin on glutamate-induced calcium signaling
      in neurons. We investigated whether apigenin affects glutamate-induced increase
      of free intracellular Ca(2+) concentration ([Ca(2+)](i)) in cultured rat
      hippocampal neurons, using fura-2-based digital calcium imaging and
      microfluorimetry. The hippocampal neurons were used between 10 and 13 days in
      culture from embryonic day 18 rats. Pretreatment of the cells with apigenin (1
      microM to 100 microM) for 5 min inhibited glutamate (100 microM, 1 min) induced
      [Ca(2+)](i) increase, concentration-dependently. Pretreatment with apigenin (30
      microM) for 5 min significantly decreased the [Ca(2+)](i) responses induced by
      two ionotropic glutamate receptor agonists, alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic (AMPA, 10 microM, 1 min) and N-methyl-D-aspartate (NMDA, 100
      microM, 1 min), and significantly inhibited the AMPA-induced peak currents.
      Treatment with apigenin also significantly inhibited the [Ca(2+)](i) response
      induced by 50 mM KCl solution, decreased the [Ca(2+)](i) responses induced by the
      metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine (DHPG,
      100 microM, 90 s), and inhibited the caffeine (10 mM, 2 min)-induced [Ca(2+)](i)
      responses. Furthermore, treatment with apigenin (30 microM) significantly
      inhibited the amplitude and frequency of 0.1 mM [Mg(2+)](o)-induced [Ca(2+)](i)
      spikes. These data together suggest that apigenin inhibits glutamate-induced
      calcium signaling in cultured rat hippocampal neurons.

PMID- 20157394
TI  - Expression of Ca-activated K Channels and Their Role in Proliferation of Rat
      Cardiac Fibroblasts.
AB  - Cardiac fibroblasts constitute one of the largest cell populations in the heart,
      and contribute to structural, biochemical, mechanical and electrical properties
      of the myocardium. Nonetheless, their cardiac functions, especially
      electrophysiological properties, have often been disregarded in studies. Ca(2+)
      activated K(+) (K(Ca)) channels can control Ca(2+) influx as well as a number of
      Ca(2+)-dependent physiological processes. We, therefore, attempted to identify
      and characterize K(Ca) channels in rat Cardiac fibroblasts. First, we showed that
      the cells cultured from the rat ventricle were cardiac fibroblasts by
      immunostaining for discoidin domain receptor 2 (DDR-2), a specific fibroblast
      marker. Secondly, we detected the expression of various K(Ca) channels by reverse
      transcription polymerase chain reaction (RT-PCR), and found all three family
      members of K(Ca) channels, including large conductance K(Ca) (BK-alpha1- and 
      beta1~4 subunits), intermediate conductance K(Ca) (IK), and small conductance
      K(Ca) (SK1~4 subunits) channels. Thirdly, we recorded BK, IK, and SK channels by
      whole cell mode patch clamp technique using their specific blockers. Finally, we
      performed cell proliferation assay to evaluate the effects of the channels on
      cell proliferation, and found that the inhibition of IK channel increased the
      cell proliferation. These results showed the existence of BK, IK, and SK channels
      in rat ventricular fibroblasts and involvement of IK channel in cell
      proliferation.

PMID- 20157395
TI  - Relaxant Effect of Spermidine on Acethylcholine and High K-induced Gastric
      Contractions of Guinea-Pig.
AB  - In our previous study, we found that spermine and putrescine inhibited
      spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach
      via inhibition of L-type voltage-dependent calcium current (VDCC(L)). In this
      study, we also studied the effect of spermidine on mechanical contractions and
      calcium channel current (I(Ba)), and then compared its effects to those by
      spermine and putrescine. Spermidine inhibited spontaneous contraction of the
      gastric smooth muscle in a concentration-dependent manner (IC(50)=1.1+/-0.11 mM).
      Relationship between inhibition of contraction and calcium current by spermidine
      was studied using 50 mM high K(+)-induced contraction: Spermidine (5 mM)
      significantly reduced high K(+) (50 mM)-induced contraction to 37+/-4.7% of the
      control (p<0.05), and inhibitory effect of spermidine on I(Ba) was also observed
      at a wide range of test potential in current/voltage (I/V) relationship. Pre- and
      post-application of spermidine (5 mM) also significantly inhibited carbachol
      (CCh) and ACh-induced initial and phasic contractions. Finally, caffeine (10 mM)
      induced contraction which is activated by Ca(2+)-induced Ca(2+) release (CICR),'
      was also inhibited by pretreatment of spermidine (5 mM). These findings suggest
      that spermidine inhibits spontaneous and CCh-induced contraction via inhibition
      of VDCC(L) and Ca(2+) releasing mechanism in guinea-pig stomach.

PMID- 20157396
TI  - Glycyrrhizin Attenuates MPTP Neurotoxicity in Mouse and MPP-Induced Cell Death in
      PC12 Cells.
AB  - The present study examined the inhibitory effect of licorice compounds
      glycyrrhizin and a metabolite 18beta-glycyrrhetinic acid on the neurotoxicity of
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and on the 1
      methyl-4-phenylpyridinium (MPP(+))-induced cell death in differentiated PC12
      cells. MPTP treatment increased the activities of total superoxide dismutase,
      catalase and glutathione peroxidase and the levels of malondialdehyde and
      carbonyls in the brain compared to control mouse brain. Co-administration of
      glycyrrhizin (16.8 mg/kg) attenuated the MPTP effect on the enzyme activities and
      formation of tissue peroxidation products. In vitro assay, licorice compounds
      attenuated the MPP(+)-induced cell death and caspase-3 activation in PC12 cells.
      Glycyrrhizin up to 100microM significantly attenuated the toxicity of MPP(+).
      Meanwhile, 18beta-glycyrrhetinic acid showed a maximum inhibitory effect at
      10microM; beyond this concentration the inhibitory effect declined. Glycyrrhizin
      and 18beta-glycyrrhetinic acid attenuated the hydrogen peroxide- or nitrogen
      species-induced cell death. Results from this study indicate that glycyrrhizin
      may attenuate brain tissue damage in mice treated with MPTP through inhibitory
      effect on oxidative tissue damage. Glycyrrhizin and 18beta-glycyrrhetinic acid
      may reduce the MPP(+) toxicity in PC12 cells by suppressing caspase-3 activation.
      The effect seems to be ascribed to the antioxidant effect.

PMID- 20157397
TI  - Testosterone relaxes rabbit seminal vesicle by calcium channel inhibition.
AB  - Recent studies have documented that testosterone relaxes several smooth muscles
      by modulating K(+) channel activities. Smooth muscles of seminal vesicles play a
      fundamental role in ejaculation, which might involve testosterone. This study was
      aimed to assess the role of testosterone in seminal vesicular motility by
      studying its effects on contractile agents and on the ion channels of single
      vesicular myocytes in a rabbit model. The contractile responses of circular
      smooth muscle strips of rabbit seminal vesicles to norepinephrine (10 microM), a
      high concentration of KCl (70 mM), and testosterone (10 microM) were observed.
      Single vesicular myocytes of rabbit were isolated using proteolytic enzymes
      including collagenase and papain. Inside-out, attached, and whole-cell
      configurations were examined using the patch clamp technique. The applications of
      10 microM norepinephrine or 70 mM KCl induced tonic contractions, and 10 microM
      testosterone (pharmacological concentration) evoked dose-dependent relaxations of
      these precontracted strips. Various K(+) channel blockers, such as
      tetraethylammonium (TEA; 10 mM), iberiotoxin (0.1 microM), 4-aminopyridine (4-AP,
      10 microM), or glibenclamide (10 microM) rarely affected these relaxations.
      Single channel data (of inside-out and attached configurations) of BK channel
      activity were also hardly affected by testosterone (10 microM). On the other
      hand, however, testosterone reduced L-type Ca(2+) currents significantly, and
      found to induce acute relaxation of seminal vesicular smooth muscle and this was
      mediated, at least in part, by Ca(2+) current inhibition in rabbit.

PMID- 20157398
TI  - Protective effect of decursinol on mouse models of sepsis: enhancement of
      interleukin-10.
AB  - The effects of decursinol on various models of sepsis were investigated. Intra
      peritoneal pretreatment of mice with various doses of decursinol (1~100 mg/kg)
      effectively suppressed lethality induced in three mouse models of experimental
      sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20
      mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of
      mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN-induced increase
      of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-alpha, IL-6
      and IL-12 levels. These results suggest that decursinol could be effective for
      prevention or treatment of sepsis.

PMID- 20157399
TI  - Assessment of Relationship between Fyn-related Kinase Gene Polymorphisms and
      Overweight/Obesity in Korean Population.
AB  - The fyn-related kinase (FRK) belongs to the tyrosine kinase family of protein
      kinases. Recent studies have shown that Frk affects pancreatic beta cell number
      during embryogenesis and promotes beta cell cytotoxic signals in response to
      streptozotocin. To investigate the genetic association between FRK polymorphisms
      and the risk of obesity in Korean population, single nucleotide polymorphisms
      (SNPs) in the FRK gene region were selected and analyzed. The body mass index
      (BMI) was calculated, and biochemical data (systolic blood pressure, diastolic
      blood pressure, hemoglobin A1C, triglyceride, total cholesterol, high density
      lipoprotein, and low density lipoprotein) of blood sample from each subject were
      also measured. One hundred fifty five healthy control and 204 overweight/obesity
      subjects were recruited. Genotype frequencies of six SNPs [rs6568920 (+8391G>A),
      rs3756772 (+56780A>G), rs3798234 (+75687C>T), rs9384970 (+68506G>A), rs1933739
      (+72978G>A), and rs9400883 (+75809A>G)] in the FRK gene were determined by
      Affymetrix Targeted Genotyping Chip data. According to the classification of
      Korean Society for the Study of Obesity, control (BMI 18 to <23) and
      overweight/obesity (BMI>/=23) subjects were recruited. For the analysis of
      genetic data, EM algorithm, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and
      Helixtree programs were used. Multiple logistic regression analysis (codominant,
      dominant, and recessive models) was performed. Age and gender as covariates were
      adjusted. For biochemical data, Student's t test was used. The mean value of BMI
      in the control and overweigh/obesity groups was 21.1+/-1.2 (mean+/-SD) and 25.6+/
      2.0, respectively. All biochemical data of the overweight/obesity group were
      statistically significance, compared with the control group. Among six SNPs, two
      linkage disequilibrium (LD) blocks were discovered. One block consisted of
      rs1933739 and rs9400883, and the other comprised rs3756772 and rs3798234. One SNP
      (rs9384970, +68506G>A) showed an association with overweight/obesity in the
      codominant model (p=0.03). Interestingly, the AA genotype distribution in the
      overweight/obesity group (n=7, 3.5%) was higher than those in the control group
      (n=1, 0.6%), which is not found in either Japanese or Chinese subjects.
      Therefore, the AA genotype of rs9384970 may be a risk factor for development of
      obesity in Korean population. The results suggest that FRK may be associated with
      overweight/obesity in Korean population.

PMID- 20157400
TI  - White Matter Damage and Hippocampal Neurodegeneration Induced by Permanent
      Bilateral Occlusion of Common Carotid Artery in the Rat: Comparison between
      Wistar and Sprague-Dawley Strain.
AB  - In order to reproduce chronic cerebral hypoperfusion as it occurs in human aging
      and Alzheimer's disease, we introduced permanent, bilateral occlusion of the
      common carotid arteries (BCCAO) in rats (Farkas et al, 2007). Here, we induced
      BCCAO in two different rat strains in order to determine whether there was a
      strain difference in the pathogenic response to BCCAO. Male Wistar and Sprague
      Dawley (SD) rats (250-270 g) were subjected to BCCAO for three weeks. Kluver
      Barrera and cresyl violet staining were used to evaluate white matter and gray
      matter damage, respectively. Wistar rats had a considerably higher mortality rate
      (four of 14 rats) as compared to SD rats (one of 15 rats) following BCCAO.
      Complete loss of pupillary light reflex occurred in all Wistar rats that
      survived, but loss of pupillary light reflex did not occur at all in SD rats.
      Moreover, BCCAO induced marked vacuolation in the optic tract of Wistar rats as
      compared to SD rats. In contrast, SD rats showed fewer CA1 hippocampal neurons
      than Wistar rats following BCCAO. These results suggest that the
      neuropathological process induced by BCCAO takes place in a region-specific
      pattern that varies according to the strain of rat involved.

PMID- 20157401
TI  - Temporal Changes of the Calcium-binding Proteins in the Medial Vestibular Nucleus
      following Unilateral Labyrinthectomy in Rats.
AB  - Calcium (Ca(2+)) is an intracellular second messenger associated with neuronal
      plasticity of the central nervous system. The calcium-binding proteins regulate
      the Ca(2+)-mediated signals in the cytoplasm and buffer the calcium
      concentration. This study examined temporal changes of three calcium-binding
      proteins (calretinin, calbindin and parvalbumin) in the medial vestibular nucleus
      (MVN) during vestibular compensation after unilateral labyrinthectomy (UL) in
      rats. Rats underwent UL, and the changes in the expression of these proteins at
      2, 6, 12, 24, 48, and 72 h were examined by immunofluorescence staining. The
      expression levels of all three proteins increased immediately after UL and
      returned to the control level by 48 h. However, the level of calretinin showed
      changes different from the other two proteins, being expressed at significantly
      higher level in the contralateral MVN than in the ipsilateral MVN 2 h after UL,
      whereas the other two proteins showed similar expression levels in both the
      ipsilateral and contralateral MVN. These results suggest that the calcium binding
      proteins have some protective activity against the increased Ca(2+) levels in the
      MVN. In particular, calretinin might be more responsive to neuronal activity than
      calbindin or parvalbumin.

PMID- 20157402
TI  - Influence of ketamine on catecholamine secretion in the perfused rat adrenal
      medulla.
AB  - The aim of the present study was to examine the effects of ketamine, a
      dissociative anesthetics, on secretion of catecholamines (CA) secretion evoked by
      cholinergic stimulation from the perfused model of the isolated rat adrenal
      gland, and to establish its mechanism of action, and to compare ketamine effect
      with that of thiopental sodium, which is one of intravenous barbiturate
      anesthetics. Ketamine (30~300microM), perfused into an adrenal vein for 60 min,
      dose- and time-dependently inhibited the CA secretory responses evoked by ACh
      (5.32 mM), high K(+) (a direct membrane-depolarizer, 56 mM), DMPP (a selective
      neuronal nicotinic NN receptor agonist, 100microM) and McN-A-343 (a selective
      muscarinic M1 receptor agonist, 100microM). Also, in the presence of ketamine
      (100microM), the CA secretory responses evoked by veratridine (a voltage
      dependent Na(+) channel activator, 100microM), Bay-K-8644 (an L-type
      dihydropyridine Ca(2+) channel activator, 10microM), and cyclopiazonic acid (a
      cytoplasmic Ca(2+)-ATPase inhibitor, 10microM) were significantly reduced,
      respectively. Interestingly, thiopental sodium (100microM) also caused the
      inhibitory effects on the CA secretory responses evoked by ACh, high K(+) , DMPP,
      McN-A-343, veratridine, Bay-K-8644, and cyclopiazonic acid. Collectively, these
      experimental results demonstrate that ketamine inhibits the CA secretion evoked
      by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the
      membrane depolarization from the isolated perfused rat adrenal gland. It seems
      likely that the inhibitory effect of ketamine is mediated by blocking the influx
      of both Ca(2+) and Na(+) through voltage-dependent Ca(2+) and Na(+) channels into
      the rat adrenal medullary chromaffin cells as well as by inhibiting Ca(2+)
      release from the cytoplasmic calcium store, which are relevant to the blockade of
      cholinergic receptors. It is also thought that, on the basis of concentrations,
      ketamine causes similar inhibitory effect with thiopental in the CA secretion
      from the perfused rat adrenal medulla.

PMID- 20157403
TI  - (-)-epigallocatechin gallate inhibits the pacemaker activity of interstitial
      cells of cajal of mouse small intestine.
AB  - The effects of (-)-epigallocatechin gallate (EGCG) on pacemaker activities of
      cultured interstitial cells of Cajal (ICC) from murine small intestine were
      investigated using whole-cell patch-clamp technique at 30 and Ca(2+) image
      analysis. ICC generated spontaneous pacemaker currents at a holding potential of 
      70 mV. The treatment of ICC with EGCG resulted in a dose-dependent decrease in
      the frequency and amplitude of pacemaker currents. SQ-22536, an adenylate cyclase
      inhibitor, and ODQ, a guanylate cyclase inhibitor, did not inhibit the effects of
      EGCG. EGCG-induced effects on pacemaker currents were not inhibited by
      glibenclamide, an ATP-sensitive K(+) channel blocker and TEA, a Ca(2+)-activated
      K(+) channel blocker. Also, we found that EGCG inhibited the spontaneous
      [Ca(2+)](i) oscillations in cultured ICC. In conclusion, EGCG inhibited the
      pacemaker activity of ICC and reduced [Ca(2+)](i) oscillations by cAMP-, cGMP-,
      ATP-sensitive K+ channel-independent manner.

PMID- 20157404
TI  - Effects of repeated citalopram treatments on chronic mild stress-induced growth
      associated protein-43 mRNA expression in rat hippocampus.
AB  - Although growth associated protein-43 (GAP-43) is known to play a significant
      role in the regulation of axonal growth and the formation of new neuronal
      connections in the hippocampus, there is only a few studies on the effects of
      acute stress on GAP-43 mRNA expression in the hippocampus. Moreover, the effects
      of repeated citalopram treatment on chronic mild stress (CMS)-induced changes in
      GAP-43 mRNA expression in the hippocampus have not been explored before. To
      explore this question, male rats were exposed to acute immobilization stress or
      CMS. Also, citalopram was given prior to stress everyday during CMS procedures.
      Acute immobilization stress significantly increased GAP-43 mRNA expression in all
      subfields of the hippocampus, while CMS significantly decreased GAP-43 mRNA
      expression in the dentate granule cell layer (GCL). Repeated citalopram treatment
      decreased GAP-43 mRNA expression in the GCL compared with unstressed controls,
      but this decrease was not further potentiated by CMS exposure. Similar decreases
      in GAP-43 mRNA expression were observed in CA1, CA3 and CA4 areas of the
      hippocampus only after repeated citalopram treatment in CMS-exposed rats. This
      result indicates that GAP-43 mRNA expression in the hippocampus may differently
      respond to acute and chronic stress, and that repeated citalopram treatment does
      not change CMS-induced decreases in GAP-43 mRNA expression in the GCL.

PMID- 20157405
TI  - Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean
      Population.
AB  - The aim of this study was to determine whether single nucleotide polymorphisms
      (SNPs) of matrix metallopeptidase 2 (MMP2) are associated with obesity. MMP2 is
      an enzyme with proteolytic activity against matrix and nonmatrix proteins,
      particularly basement membrane constituents. To identify the relationship between
      polymorphisms of MMP2 and overweight/obese, we genotyped 5 SNPs (rs17242319,
      rs1053605, rs243849, rs2287074, and rs10775332) of the coding region of MMP2
      using the Golden Gate assay on an Illumina BeadStation 500 GX. One hundred and
      forty two overweight/obese (BMI >/=23) and 145 normal (BMI 18 to <23) subjects
      were analyzed. SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree
      programs were used for the analysis of genetic data. A linkage disequilibrium
      (LD) block was discovered among the 5 SNPs selected, including rs17242319,
      rs1053605, rs243849, and rs2287074. Of the 5 polymorphisms, 2 synonymous SNPs
      [rs17242319 (Gly226Gly) and rs10775332 (Phe602Phe)] were found significant
      associations with overweight/obese. Recently, rs1132896 replaced rs17242319 as a
      new number (SNP database, BUILD 129). In haplotype analysis using Haploview, a
      haplotype (haplotype: CCCA) containing a meaningful polymorphism (rs17242319) was
      found to be significantly different. The results suggest that MMP2 may be
      associated with overweight/obese in Korean population.

PMID- 20157406
TI  - Incidence of calcification of the trochlear apparatus in the orbit.
AB  - PURPOSE: To quantify the incidence of asymptomatic incidental trochlear
      calcifications and to describe their clinical features. METHODS: We
      retrospectively reviewed orbital computed tomography (CT) scans of 216 patients
      to identify the presence of trochlear calcifications. We analyzed the prevalence,
      age distribution, and gender preponderance of trochlear calcifications. We also
      examined age-specific prevalence rates for trochlear calcifications, as well as
      their relationship to systemic disease. RESULTS: The mean age of patients was
      26.8 years. Trochlear calcifications were observed in 35 (16%) of the 216
      patients, and 18 of the 35 patients had bilateral calcifications. The rate of
      trochlear calcification was higher in males; 32 (20.9%) of 153 male patients had
      trochlear calcifications, compared with 3 (4.8%) of 63 female patients. Age,
      hypertension, diabetes mellitus, and thyroid disease were not significantly
      associated with the incidence of trochlear calcifications. CONCLUSIONS:
      Incidental asymptomatic orbital calcification is more commonly observed on CT
      images than we expected and occurs predominantly in male patients. Understanding
      this to be a relatively common, benign finding may help us to rule out foreign
      bodies and other pathologic conditions.

PMID- 20157407
TI  - Lower eyelid epiblepharon associated with lower eyelid retraction.
AB  - PURPOSE: To describe a series of patients with lower eyelid epiblepharon
      associated with lower eyelid retraction. METHODS: We retrospectively reviewed the
      medical records of patients who underwent surgery for lower eyelid retraction,
      epiblepharon, or thyroid-associated ophthalmopathy (TAO) between October 1999 and
      March 2007. Patients with both lower eyelid retraction and epiblepharon on
      preoperative examination were included in this study. RESULTS: Twenty-seven
      eyelids of 20 patients with both lower eyelid retraction and epiblepharon were
      enrolled. The underlying causes of lower eyelid retraction included congenital
      retraction (seven eyelids), congenital fibrosis of the extraocular muscles
      (CFEOM; seven eyelids), TAO (seven eyelids), post-operative cicatricial
      retraction (five eyelids), and facial nerve palsy (one eyelid). Eight of 27
      eyelids were successfully corrected after the repair of retraction without the
      repair of epiblepharon, regardless of the cause of lower eyelid retraction.
      Another four eyelids with epiblepharon associated with TAO resolved after only
      orbital decompression. Cilia-everting sutures were additionally applied for
      epiblepharon in another 14 eyelids, 12 of which did not require the excision of a
      skin fold or the orbicularis muscles. Only one eyelid with mild retraction and
      epiblepharon underwent simple epiblepharon repair. Recurrence of retraction or
      epiblepharon developed in three eyelids during follow-up. CONCLUSIONS: In cases
      with both lower eyelid retraction and epiblepharon, the retraction should be
      repaired first, and then the epiblepharon can be corrected selectively according
      to the severity of the case.

PMID- 20157408
TI  - Risk factors for endothelial cell loss after phacoemulsification: comparison in
      different anterior chamber depth groups.
AB  - PURPOSE: To assess the risk factors for endothelial cell loss after
      phacoemulsification with implantation of intraocular lens according to anterior
      chamber depth (ACD). METHODS: This prospective study included 94 eyes of 94
      patients undergoing phacoemulsification cataract surgery. To assess the risk
      factors for corneal endothelial cell loss, we examined seven variables at 1 day,
      1 week, 6 weeks, and 12 weeks postoperatively in each ACD-stratified group.
      RESULTS: Multiple linear regression analysis showed that the only variable
      influencing the percentage decrease in corneal endothelial cell density
      throughout the postoperative follow-up period in the long ACD group (ACD III) was
      nucleosclerosis. The variables influencing the percentage decrease in corneal
      endothelial cell density in the short ACD group (ACD I) at one day and one week
      postoperatively were corneal incisional tunnel length and nucleosclerosis.
      CONCLUSIONS: Risk factors for endothelial cell loss after phaoemulsification were
      different according to ACD. Long corneal tunnel length can be one of the risk
      factors for endothelial cell loss in short ACD eyes.

PMID- 20157409
TI  - Diabetic retinopathy and peripapillary retinal thickness.
AB  - PURPOSE: To assess the diagnostic efficacy of macular and peripapillary retinal
      thickness measurements for the staging of diabetic retinopathy (DR) and the
      prediction of disease progression. METHODS: In this prospective study, 149
      diabetic patients (149 eyes) and 50 non-diabetic control subjects were included.
      Baseline optical coherence tomography was employed to measure retinal thickness
      in the macula (horizontal, vertical, and central) and the peripapillary zone
      (superior, inferior, nasal, and concentric to the optic disc). Seven baseline
      parameters were correlated with the DR stages identified by fluorescein
      angiography. Baseline retinal thickness was compared between groups of patients
      requiring panretinal photocoagulation (PRP) within 6 months (PRP group) and
      patients not requiring PRP (No-PRP group). RESULTS: Macular and peripapillary
      retinal thicknesses in diabetic subjects were significantly greater than that in
      normal controls (p<0.05). All retinal thickness parameters, and particularly
      peripapillary circular scans, tended to increase with increasing DR severity
      (p<0.05). The baseline thicknesses of the peripapillary circular scans were
      greater in the PRP group than in the no-PRP group (p<0.05). CONCLUSIONS:
      Peripapillary retinal thickness may prove to be a useful criterion for DR
      severity and may also serve as an indicator of disease progression.

PMID- 20157410
TI  - Circadian blood pressure and intraocular pressure patterns in normal tension
      glaucoma patients with undisturbed sleep.
AB  - PURPOSE: To investigate and compare the circadian pattern of blood pressure (BP),
      intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) while
      experiencing undisturbed sleep in normal-tension glaucoma (NTG) and non-glaucoma
      control patient groups. METHODS: Twenty-four eyes from 24 patients diagnosed with
      NTG and 22 eyes from 22 control group patients were enrolled. Systolic BP,
      diastolic BP and IOP were measured every two hours except for the period of time
      from 1 AM to 7 AM in the NTG group and from 11 PM to 7 AM in the control group
      over a one-day period. IOP and hemodynamic parameters were then compared between
      the two groups. NTG patients were subdivided according to the degree of morning
      BP dip and IOP, and hemodynamic parameters and visual field indices (mean
      deviation and pattern standard deviation) were also compared among these
      subgroups. RESULTS: There were no significant differences in mean systolic BP,
      mean diastolic BP and mean arterial pressure (MAP) between the NTG and the
      control groups. The NTG group showed a significantly large morning BP dip
      compared to the control group (7.1+/-4.2% vs. 3.8+/-3.4%, p=0.022). However,
      there were no significant differences in mean or fluctuation of MOPP between the
      two groups. Morning over-dippers showed significantly large MAP and MOPP
      fluctuations compared to non-dippers and dippers, while there were no significant
      differences in visual field indices among the three subgroups. CONCLUSIONS: NTG
      patients showed significant morning BP dips compared to the control group. The
      marked morning BP dip was associated with significantly large MAP or MOPP
      fluctuations but was not associated with visual field indices.

PMID- 20157411
TI  - A novel therapeutic target in inflammatory uveitis: transglutaminase 2 inhibitor.
AB  - PURPOSE: Our goal was to investigate the effects of inhibition of
      transglutaminase 2 (TGase 2) on endotoxin-induced uveitis (EIU) METHODS: EIU was
      induced in female Lewis rats by single footpad injections of 200 microg of
      lipopolysaccharide (LPS). TGase 2 inhibitors were administered intraperitoneally
      30 minutes before and at the time of LPS administration. Rats were sacrificed 24
      hours after injection, and the effects of the TGase 2 inhibitors were evaluated
      by the number of intraocular inflammatory cells present on histologic sections
      and by measuring the TGase 2 activity and TGase products in the aqueous humor
      (AqH). TGase 2 substrates were also assayed in AqH from uveitis patients.
      RESULTS: Clinical indications of EIU, the number of cells present on histologic
      sections, and TGase 2 activity in AqH increased in a time-dependent manner,
      peaking 24 hours after LPS injection. Inflammation in EIU was significantly
      reversed by treatment with TGase inhibitors. A 23-kDa cross-linked TGase
      substrate was identified in the AqH from EIU rats and uveitis patients. MALDI-TOF
      analysis showed that this substrate in uveitis patients was human Ig kappa chain
      C region. CONCLUSIONS: TGase 2 activity and its catalytic product were increased
      in the AqH of EIU rats. TGase 2 inhibition attenuated the degree of inflammation
      in EIU. Safe and stable TGase inhibitors may have great potential for the
      treatment of inflammatory uveitis.

PMID- 20157412
TI  - Differential expression of stem cell markers and vascular endothelial growth
      factor in human retinoblastoma tissue.
AB  - PURPOSE: To investigate the relationship between vascular endothelial growth
      factor (VEGF) and the cancer stem cell-vascular niche complex in human
      retinoblastoma tissue. METHODS: Six human retinoblastoma specimens primarily
      enucleated for Reese-Ellsworth classification stage 5a were stained to detect
      cancer stem cell markers, including ABCG2 for the stem cell marker and MCM2 for
      the neural stem cell marker, as well as to detect VEGF for the angiogenic
      cytokine. Using immunofluorescence, the expression of these proteins was
      analyzed, and their relative locations noted. RESULTS: In non-neoplastic retina
      of tumor-bearing eyes, ABCG2 and MCM2 were sporadically expressed in the ganglion
      cell layer and the inner nuclear layer, whereas VEGF was sporadically expressed
      in inner retina where retinal vessels are abundantly distributed. In the tumor,
      ABCG2 was strongly expressed out of Wintersteiner rosettes, whereas MCM2 and VEGF
      were strongly stained in the rosettes. Interestingly, the outer portion of the
      rosettes was positive for MCM2, and the inner portion of the rosettes was
      positive for VEGF. CONCLUSIONS: Our data demonstrated that MCM2 and VEGF are
      strongly expressed in the rosettes of the tumor, which were far from the area of
      ABCG2-positive cells. Although VEGF might not directly contribute to the cancer
      stem cell-vascular niche complex, it could play some role in the differentiation
      of tumor cells to build up the rosettes.

PMID- 20157413
TI  - Cutaneous leishmaniasis of the lid: a report of nine cases.
AB  - Leishmaniasis is a parasitic disease caused by Leishmania species and is
      classified into three forms; cutaneous, mucocutaneous, and visceral. The eyelid
      is a rare site involved by leishmaniasis and only makes up 2.5% of cases with
      cutaneous leishmaniasis (CL). Although CL can affect both upper and lower lids on
      either their outer or inner aspects, the lateral canthus is most often affected.
      The most common aspect of lid leishmaniasis is chalazion-like lesions but
      ulcerous, phagedenic, cancer-like forms, and unilateral chronic granulomatous
      blepharitis may be observed. When the lid is involved, the disease is usually
      self-limiting; healing usually takes up to one year, hence early diagnosis and
      treatment are important. The diagnosis is based on a high index of suspicion
      regarding the endemicity of the disease in the region. Response to treatment in
      lid CL cases is quite satisfactory. In this article, we report nine cases of lid
      leishmaniasis with satisfactory responses to intralesional meglumine antimoniate.

PMID- 20157414
TI  - A case of ciliary body melanocytoma presenting as a painful iris mass.
AB  - We report a case of ciliary body melanocytoma in a Korean patient, which
      presented as an intermittently painful pigmented iris mass and was successfully
      managed by iridocyclectomy. A 52-year-old healthy man presented with an
      irregularly-shaped and heavily-pigmented mass at the iris root of his right eye.
      Visual acuity of the right eye was 20/20 with normal intraocular pressure.
      Ultrasound biomicroscopy showed a 1.5x1.3-mm ciliary-body mass with extension
      into the iris root. Iridocyclectomy with scleral resection under a lamellar
      scleral flap was performed, and the histopathologic features of the resected
      tissue were consistent with melanocytoma of the ciliary body. The patient's
      visual acuity remained 20/20 with good postoperative cosmesis. During one year of
      follow-up, no signs of tumor recurrence were seen, and the patient reported
      resolution of the intermittent ocular pain in the involved eye.

PMID- 20157415
TI  - Subconjunctival bevacizumab as an adjunct to trabeculectomy in eyes with
      refractory glaucoma: a case series.
AB  - This prospective observational case series study included 6 eyes of 6 consecutive
      glaucomatous patients. Each patient underwent trabeculectomy with mitomycin C,
      and received a 1.25 mg of subconjunctival bevacizumab injection at completion of
      the trabeculectomy. Study eyes included two with neovascular glaucoma, three with
      uveitic glaucoma, and one with secondary glaucoma following vitrectomy. All eyes
      had undergone failed glaucoma laser/surgical treatment or an intraocular surgical
      procedure. Intraocular pressure (IOP) at the following postoperative visits:
      preoperative, 1 week, 1 month, 2 months, 3 months, and 6 months, was measured. We
      also evaluated postoperative bleb findings and complications. IOP measured at
      each visit was 37.5+/-14.4 mmHg, 6.2+/-3.4 mmHg, 8.3+/-7.2 mmHg, 12.0+/-4.4 mmHg,
      10.8+/-3.1 mmHg, and 12.2+/-3.3 mmHg, respectively, for each visit. All eyes had
      functioning blebs with normal IOP at postoperative 6 months with no additional
      IOP-lowering medication.

PMID- 20157416
TI  - A case of acquired Brown syndrome after surgical repair of a medial orbital wall
      fracture.
AB  - A case of acquired Brown syndrome caused by surgical repair of medial orbital
      wall fracture is reported in the present paper. A 23-year-old man presented at
      the hospital with right periorbital trauma. Although the patient did not complain
      of any diplopia, the imaging study revealed a blow-out fracture of the medial
      orbital wall. Surgical repair with a calvarial bone autograft was performed at
      the department of plastic surgery. The patient was referred to the ophthalmologic
      department due to diplopia that newly developed after surgery. The prism cover
      test at distant fixation showed hypotropia of the right eye, which was 4 prism
      diopters (PD) in primary gaze, 20 PD in left gaze, while orthophoric in right
      gaze. Eye movement of the right eye was markedly limited on elevation in
      adduction with normal elevation in abduction with intorsion in the right eye
      present. Forced duction test of the right eye showed restricted elevation in
      adduction. Computerized tomography scan of the orbits showed the right superior
      oblique muscle was entrapped between the autografted bone fragment and posterior
      margin of the fracture. When repairing medial orbital wall fracture that causes
      Brown syndrome, surgeons should always be careful of entrapment of the superior
      oblique muscle if the implant is inserted without identifying the superior and
      posterior margin of the orbital fracture site.

PMID- 20157417
TI  - A case of decreased visual field after uneventful cataract surgery: nonarteritic
      anterior ischemic optic neuropathy.
AB  - The purpose of this article is to report a case of nonarteritic anterior ischemic
      optic neuropathy (NAION) after uneventful cataract surgery. A 53-year-old
      Filipina underwent cataract surgery. She had a small optic disc with cup-to-disc
      ratio of 0.2 in the left eye and 0.3 in the right eye. On the first postoperative
      day, the uncorrected visual acuity (UCVA) was 20/20, with an intraocular pressure
      (IOP) of 20 mmHg in the left eye. At one week after operation, the UCVA was 20/20
      and the IOP was 15 mmHg. Three weeks later, she underwent cataract surgery in the
      right eye. On the first postoperative day, her UCVA was 20/20 in both eyes, but
      she complained of a visual field decrease in the left eye. A relative afferent
      pupillary defect (RAPD) was noted and the optic disc was pallid and swollen
      diffusely. A red-free photo showed defect surrounding the optic disc. A visual
      field test showed tunnel vision sparing the central vision. In this report, the
      authors hypothesize an association between cataract extraction and delayed NAION.
      Since the risk of NAION in the fellow eye is 30-50%, visual acuity, visual field,
      fundus exam and RAPD should be routinely checked.

PMID- 20157418
TI  - One sister and brother with mirror image myopic anisometropia.
AB  - We report a case of one sister and brother with mirror image myopic
      anisometropia. One sister and brother complained visual disturbance. The sister
      was 10 years 11 months old, and brother was 8 years 4 months old. Full ophthalmic
      examinations were performed, including slit lamp examination, intraocular
      pressure, keratometry, anterior chamber depth, axial length, fundus examination
      and the cycloplegic refraction. The cycloplegic refractive power was -15.50 dpt
      cyl.+4.50 dpt Ax 85 degrees (right eye), -1.00 dpt cyl.+0.50 dpt Ax 90 degrees
      (left eye) in the sister; -1.75 dpt cyl.+2.25 dpt Ax 90 degrees (right eye), 
      9.50 dpt cyl.+4.00 dpt Ax 80 degrees (left eye) in the brother. The co-occurrence
      of severe myopic anisometropia in a sister and brother is extremely rare. The
      present case suggests that severe myopic anisometropia may be related by genetic
      inheritance.

PMID- 20157419
TI  - Carbohydrate vs protein supplementation for recovery of neuromuscular function
      following prolonged load carriage.
AB  - BACKGROUND: This study examined the effect of carbohydrate and whey protein
      supplements on recovery of neuromuscular function after prolonged load carriage.
      METHODS: TEN MALE PARTICIPANTS (BODY MASS: 81.5 +/- 10.5 kg, age: 28 +/- 9 years,
      O(2)max: 55.0 +/- 5.5 ml.kg(-1).min(-1)) completed three treadmill walking tests
      (2 hr, 6.5 km.h(-1)), carrying a 25 kg backpack consuming 500 ml of either: (1)
      Placebo (flavoured water) [PLA], (2) 6.4% Carbohydrate Solution [CHO] or (3) 7.0%
      Whey Protein Solution [PRO]. For three days after load carriage, participants
      consumed two 500 ml supplement boluses. Muscle performance was measured before
      and at 0, 24, 48 and 72 h after load carriage, during voluntary and electrically
      stimulated contractions. RESULTS: Isometric knee extension force decreased
      immediately after load carriage with no difference between conditions. During
      recovery, isometric force returned to pre-exercise values at 48 h for CHO and PRO
      but at 72 h for PLA. Voluntary activation decreased immediately after load
      carriage and returned to pre-exercise values at 24 h in all conditions (P =
      0.086). During recovery, there were no differences between conditions for the
      change in isokinetic peak torque. Following reductions immediately after load
      carriage, knee extensor and flexor peak torque (60 degrees .s(-1)) recovered to
      pre-exercise values at 72 h. Trunk extensor and flexor peak torque (15 degrees
      .s(-1)) recovered to pre-exercise values at 24 h (P = 0.091) and 48 h (P =
      0.177), respectively. CONCLUSION: Recovery of neuromuscular function after
      prolonged load carriage is improved with either carbohydrate or whey protein
      supplementation for isometric contractions but not for isokinetic contractions.

PMID- 20157420
TI  - Spectrum of musculo-skeletal disorders in sickle cell disease in Lagos, Nigeria.
AB  - BACKGROUND: Sickle cell anemia (SCA) is a common genetic disease in Nigeria. Past
      studies from West Africa focused on isolated aspects of its medical and surgical
      presentations. To the best of our knowledge, the musculo-skeletal presentations
      amongst Nigerians with SCA have not been documented in a single all encompassing
      study. This work aims to prospectively document the musculo-skeletal disease
      burden among SCA patients. METHODS: In a prospective study of 318 consecutive
      patients with genotype-confirmed SCA at the Lagos University Teaching Hospital
      (LUTH), the musculo-skeletal pathologies, anatomic sites, grade of disease, age
      at presentation and management outcome were recorded over a one-year period. Data
      obtained were analyzed using Epi-Info software version 6.0. Data are presented as
      frequencies (%) and mean values (SD) as appropriate. RESULTS: The HbSS genotype
      occurred in 296 (93.0%), while 22 (7.0%) were HbSC. 100 (31.4%) patients with
      average presenting haemoglobin concentration of 8.2 g/100 ml in the study group,
      presented with 131 musculo-skeletal pathologies in 118 anatomic sites.
      Osteomyelitis 31 (31%) and septic arthritis 19 (19%) were most commonly observed
      in children less than 10 years. Skin ulcers and avascular necrosis (AVN) occurred
      predominantly in the older age groups, with frequencies of 13 (13.0%) and 26
      (26.0%) respectively. 20 (71.5%) of diagnosed cases of AVN presented with
      radiological grade 4 disease. The lower limbs were involved in 84 (71.1%) of
      sites affected. Lesions involving the spine were rare 11 (0.9%). Multiple
      presentations occurred in 89 (28.0%) of patients; 62 (69.7%) of which were
      children below 10 years. CONCLUSIONS: Musculo-skeletal complications are common
      features of sickle cell anaemia seen in 31.4%. Infectious aetiologies predominate
      with long bones and joints of lower limbs more commonly affected by osteomyelitis
      and septic arthritis. Healthcare providers managing SCA should be aware of the
      potential morbidity and mortality of these conditions to ensure early diagnosis
      and adequate management.

PMID- 20157421
TI  - Clinical and arthroscopic findings in recreationally active patients.
AB  - OBJECTIVE: To examine the diagnostic accuracy of standard clinical tests for the
      shoulder in recreational athletes with activity related pain. DESIGN: Cohort
      study with index test of clinical examination and reference standard of
      arthroscopy. SETTING: Sports Medicine clinic in Sheffield, U.K. PARTICIPANTS: 101
      recreational athletes (82 male, 19 female; mean age 40.8 +/- 14.6 years) over a
      six year period. INTERVENTIONS: Bilateral evaluation of movements of the shoulder
      followed by standardized shoulder tests, formulation of clinical diagnosis and
      shoulder arthroscopy conducted by the same surgeon. MAIN OUTCOME MEASUREMENTS:
      Sensitivity, specificity, likelihood ratio for a positive test and over-all
      accuracy of clinical examination was examined retrospectively and compared with
      arthroscopy. RESULTS: Isolated pathology was rare, most patients (72%) having
      more than one injury recorded. O'Brien's clinical test had a mediocre sensitivity
      (64%) and over-all accuracy (54%) for diagnosing SLAP lesions. Hawkins test and
      Jobe's test had the highest but still not impressive over-all accuracy (67%) and
      sensitivity (67%) for rotator cuff pathology respectively. External and internal
      impingement tests showed similar levels of accuracy. When a positive test was
      observed in one of a combination of shoulder tests used for diagnosing SLAP
      lesions or rotator cuff disease, sensitivity increased substantially whilst
      specificity decreased. CONCLUSIONS: The diagnostic accuracy of isolated standard
      shoulder tests in recreational athletes was over-all very poor, potentially due
      to the majority of athletes (71%) having concomitant shoulder injuries. Most
      likely, this means that many of these injuries are missed in general practice and
      treatment is therefore delayed. Clinical examination of the shoulder should
      involve a combination of clinical tests in order to identify likely intra
      articular pathology which may warrant referral to specialist for surgery.

PMID- 20157422
TI  - The prosurvival activity of ascites against TRAIL is associated with a shorter
      disease-free interval in patients with ovarian cancer.
AB  - BACKGROUND: The production of ascites is a common complication of ovarian cancer.
      Ascites constitute a unique tumor microenvironment that may affect disease
      progression. In this context, we recently showed that ovarian cancer ascites may
      protect tumor cells from TRAIL-induced apoptosis. In this study, we sought to
      determine whether the prosurvival effect of ascites affects disease-free
      intervals. METHODS: Peritoneal fluids were obtained from 54 women undergoing
      intra-abdominal surgery for suspected ovarian cancer (44 cancers and 10 benign
      diseases). The ability of peritoneal fluids to protect from TRAIL was assessed in
      the ovarian cancer cell line CaOV3, and IC(50 )were determined. The anti
      apoptotic activity of 6 ascites against cisplatin, paclitaxel, doxorubicin,
      etoposide and vinorelbine was also assessed in CaOV3 cells, and the prosurvival
      activity of two ascites was assessed in 9 primary ovarian cancer cultures.
      RESULTS: Among the 54 peritoneal fluids tested, inhibition of TRAIL cytotoxicity
      was variable. Fluids originating from ovarian cancer were generally more
      protective than fluids from non-malignant diseases. Most of the 44 ovarian cancer
      ascites increased TRAIL IC(50 )and this inhibitory effect did not correlate
      strongly with the protein concentration in these ascites or the levels of serum
      CA125, a tumor antigen which is used in the clinic as a marker of tumor burden.
      The effect of ascites on cisplatin- and paclitaxel-induced cell death was
      assessed with 4 ascites having inhibitory effect on TRAIL-induced cell death and
      2 that do not. The four ascites with prosurvival activity against TRAIL had some
      inhibitory on cisplatin and/or paclitaxel. Two ovarian cancer ascites, OVC346 and
      OVC509, also inhibited TRAIL cytotoxicity in 9 primary cultures of ovarian tumor
      and induced Akt activation in three of these primary cultures. Among a cohort of
      35 patients with ascites, a threshold of TRAIL IC(50 )with ascites/IC(50 )without
      ascites > 2 was associated with shorter disease-free interval. CONCLUSIONS: The
      prosurvival activity of ascites against TRAIL is associated with shorter disease
      free interval, which may be explained, at least in part, by ascites-induced
      cisplatin/paclitaxel resistance. Our findings suggest that ascites may contain
      prosurvival factors that protect against TRAIL and chemotherapy and consequently
      affect disease progression.

PMID- 20157423
TI  - Differences in the epigenetic and reprogramming properties of pluripotent and
      extra-embryonic stem cells implicate chromatin remodelling as an important early
      event in the developing mouse embryo.
AB  - BACKGROUND: During early mouse development, two extra-embryonic lineages form
      alongside the future embryo: the trophectoderm (TE) and the primitive endoderm
      (PrE). Epigenetic changes known to take place during these early stages include
      changes in DNA methylation and modified histones, as well as dynamic changes in
      gene expression. RESULTS: In order to understand the role and extent of chromatin
      based changes for lineage commitment within the embryo, we examined the
      epigenetic profiles of mouse embryonic stem (ES), trophectoderm stem (TS) and
      extra-embryonic endoderm (XEN) stem cell lines that were derived from the inner
      cell mass (ICM), TE and PrE, respectively. As an initial indicator of the
      chromatin state, we assessed the replication timing of a cohort of genes in each
      cell type, based on data that expressed genes and acetylated chromatin domains,
      generally, replicate early in S-phase, whereas some silent genes, hypoacetylated
      or condensed chromatin tend to replicate later. We found that many lineage
      specific genes replicate early in ES, TS and XEN cells, which was consistent with
      a broadly 'accessible' chromatin that was reported previously for multiple ES
      cell lines. Close inspection of these profiles revealed differences between ES,
      TS and XEN cells that were consistent with their differing lineage affiliations
      and developmental potential. A comparative analysis of modified histones at the
      promoters of individual genes showed that in TS and ES cells many lineage
      specific regulator genes are co-marked with modifications associated with active
      (H4ac, H3K4me2, H3K9ac) and repressive (H3K27me3) chromatin. However, in XEN
      cells several of these genes were marked solely by repressive modifications (such
      as H3K27me3, H4K20me3). Consistent with TS and XEN having a restricted
      developmental potential, we show that these cells selectively reprogramme somatic
      cells to induce the de novo expression of genes associated with extraembryonic
      differentiation. CONCLUSIONS: These data provide evidence that the
      diversification of defined embryonic and extra-embryonic lineages is accompanied
      by chromatin remodelling at specific loci. Stem cell lines from the ICM, TE and
      PrE can each dominantly reprogramme somatic cells but reset gene expression
      differently, reflecting their separate lineage identities and increasingly
      restricted developmental potentials.

PMID- 20157424
TI  - Real-time in vivo imaging of p16gene expression: a new approach to study
      senescence stress signaling in living animals.
AB  - Oncogenic proliferative signals are coupled to a variety of growth inhibitory
      processes. In cultured primary human fibroblasts, for example, ectopic expression
      of oncogenic Ras or its downstream mediator initiates cellular senescence, the
      state of irreversible cell cycle arrest, through up-regulation of cyclin
      dependent kinase (CDK) inhibitors, such as p16(INK4a). To date, much of our
      current knowledge of how human p16(INK4a )gene expression is induced by oncogenic
      stimuli derives from studies undertaken in cultured primary cells. However, since
      human p16(INK4a )gene expression is also induced by tissue culture-imposed
      stress, it remains unclear whether the induction of human p16(INK4a )gene
      expression in tissue-cultured cells truly reflects an anti-cancer process or is
      an artifact of tissue culture-imposed stress. To eliminate any potential problems
      arising from tissue culture imposed stress, we have recently developed a
      bioluminescence imaging (BLI) system for non-invasive and real-time analysis of
      human p16(INK4a )gene expression in the context of a living animal. Here, we
      discuss the molecular mechanisms that direct p16(INK4a )gene expression in vivo
      and its potential for tumor suppression.

PMID- 20157425
TI  - Unicystic ameloblastoma of the mandible--an unusual case report and review of
      literature.
AB  - Ameloblastoma is a true neoplasm of odontogenic epithelial origin. It is the
      second most common odontogenic neoplasm, and only odontoma outnumbers it in
      reported frequency of occurrence. Its incidence, combined with its clinical
      behavior, makes ameloblastoma the most significant odontogenic neoplasm.
      Unicystic ameloblastoma (UA) refers to those cystic lesions that show clinical,
      radiographic, or gross features of a mandibular cyst, but on histologic
      examination show a typical ameloblastomatous epithelium lining part of the cyst
      cavity, with or without luminal and/or mural tumor growth. It accounts for 5-15%
      of all intraosseous ameloblastomas. We report a case of unicystic ameloblastoma
      in a 30-year-old female, and review the literature.

PMID- 20157426
TI  - Pattern and determinants of BCG immunisation delays in a sub-Saharan African
      community.
AB  - BACKGROUND: Childhood immunisation is recognised worldwide as an essential
      component of health systems and an indispensable indicator of quality of care for
      vaccine-preventable diseases. While performance of immunisation programmes is
      more commonly measured by coverage, ensuring that every child is immunised at the
      earliest/appropriate age is an important public health goal. This study therefore
      set out to determine the pattern and predictors of Bacille de Calmette-Guerin
      (BCG) immunisation delays in the first three months of life in a Sub-Saharan
      African community where BCG is scheduled at birth in order to facilitate
      necessary changes in current policy and practices for improved services. METHODS:
      A cross-sectional study in which immunisation delays among infants aged 0-3
      months attending community-based BCG clinics in Lagos, Nigeria over a 2-year
      period from July 2005 to June 2007 were assessed by survival analysis and
      associated factors determined by multivariable logistic regression. Population
      attributable risk (PAR) was computed for the predictors of delays. RESULTS: BCG
      was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants
      enrolled, 3380 (65.4%) were immunised within two weeks and a further 1265 (24.5%)
      by six weeks. A significantly higher proportion of infants born in hospitals were
      vaccinated in the first six weeks compared to those born outside hospitals.
      Undernourishment was predictive of delays beyond 2 and 6 weeks while treated
      hyperbilirubinaemia was associated with decreased odds for any delays. Lack of
      antenatal care and multiple gestations were also predictive of delays beyond 6
      weeks. Undernourishment was associated with the highest PAR for delays beyond 2
      weeks (18.7%) and 6 weeks (20.8%). CONCLUSIONS: BCG immunisation is associated
      with significant delays in this setting and infants at increased risk of delays
      can be identified and supported early possibly through improved maternal uptake
      of antenatal care. Combining BCG with subsequent immunisation(s) at 6 weeks for
      infants who missed the BCG may be considered.

PMID- 20157427
TI  - Attentional networks in developmental dyscalculia.
AB  - BACKGROUND: Very little is known about attention deficits in developmental
      dyscalculia, hence, this study was designed to provide the missing information.
      We examined attention abilities of participants suffering from developmental
      dyscalculia using the attention networks test - interactions. This test was
      designed to examine three different attention networks--executive function,
      orienting and alerting--and the interactions between them. METHODS: Fourteen
      university students that were diagnosed as suffering from developmental
      dyscalculia--intelligence and reading abilities in the normal range and no
      indication of attention-deficit hyperactivity disorder--and 14 matched controls
      were tested using the attention networks test-interactions. All participants were
      given preliminary tests to measure mathematical abilities, reading, attention and
      intelligence. RESULTS: The results revealed deficits in the alerting network--a
      larger alerting effect--and in the executive function networks--a larger
      congruity effect in developmental dyscalculia participants. The interaction
      between the alerting and executive function networks was also modulated by group.
      In addition, developmental dyscalculia participants were slower to respond in the
      non-cued conditions. CONCLUSIONS: These results imply specific attentional
      deficits in pure developmental dyscalculia. Namely, those with developmental
      dyscalculia seem to be deficient in the executive function and alertness
      networks. They suffer from difficulty in recruiting attention, in addition to the
      deficits in numerical processing.

PMID- 20157428
TI  - Pleomorphic adenoma of minor salivary gland with therapeutic misadventure: a rare
      case report.
AB  - BACKGROUND: The benign tumors of nasopharynx are least encountered tumors in
      otolaryngology, as nasopharynx is considered one of notorious anatomical site for
      the malignant tumors. Pleomorphic adenoma of the minor salivary gland of
      nasopharynx and parapharyngeal space is rare. We present a pleomorphic adenoma of
      minor salivary gland which was mismanaged. CASE PRESENTATION: An adult male
      presented with left nostril obstruction for five months. The examination found
      big mass extending from nasopharynx to oropharynx. On CT scan, this tumor was
      quite big and extending to the parapharyngeal space. The FNAB found it a
      carcinoma but it did not respond to radiotherapy. The excision biopsy of tumor
      revealed it as pleomorphic adenoma. We found only five published reports on this
      tumor arising from nasopharynx. DISCUSSION AND CONCLUSION: Although, in this case
      report exact origin of the tumor could not be ascertained as it also appeared to
      be a parapharyngeal tumor but we kept the possibility of a nasopharyngeal tumor
      on the basis of clinical features. The pleomorphic adenoma of nasopharynx is
      rare. It can be misdiagnosed as malignant epithelial tumor on histopathology. The
      differentiation from its malignant variant is also difficult. A possibility of
      benign tumor should always be kept in nasopharyngeal growth with no evidence of
      metastasis, and histopathological diagnosis of growth should be available before
      any definitive treatment.

PMID- 20157429
TI  - Kinetics of diffusion-controlled enzymatic reactions with charged substrates.
AB  - The Debye-Huckel limiting law (DHL) has often been used to estimate rate
      constants of diffusion-controlled reactions under different ionic strengths. Two
      main approximations are adopted in DHL: one is that the solution of the
      linearized Poisson-Boltzmann equation for a spherical cavity is used to estimate
      the excess electrostatic free energy of a solution; the other is that details of
      electrostatic interactions of the solutes are neglected. This makes DHL
      applicable only at low ionic strengths and dilute solutions (very low
      substrate/solute concentrations). We show in this work that through numerical
      solution of the Poisson-Nernst-Planck equations, diffusion-reaction processes can
      be studied at a variety of conditions including realistically concentrated
      solutions, high ionic strength, and certainly with non-equilibrium charge
      distributions. Reaction rate coefficients for the acetylcholine
      acetylcholinesterase system are predicted to strongly depend on both ionic
      strength and substrate concentration. In particular, they increase considerably
      with increase of substrate concentrations at a fixed ionic strength, which is
      open to experimental testing. This phenomenon is also verified on a simple model,
      and is expected to be general for electrostatically attracting enzyme-substrate
      systems.PACS Codes: 82.45.Tv, 87.15.VvMSC Codes: 92C30.

PMID- 20157430
TI  - Spontaneous rupture of a large non-parasitic liver cyst: a case report.
AB  - INTRODUCTION: Non-parasitic hepatic cysts are benign entities, occur rarely (5%
      of the population), and in the majority of cases, are asymptomatic. Cysts can
      cause symptoms when they become large and produce bile duct compression or portal
      hypertension, and also when complications such as rupture, infection or
      hemorrhage take place. CASE PRESENTATION: We present the case of a 70-year-old
      Greek-Caucasian man with a large, asymptomatic and non-parasitic liver cyst that
      presented as an acute surgical abdominal emergency after spontaneous rupture into
      the peritoneal cavity. CONCLUSIONS: We present an extremely rare complication of
      simple liver cyst, its rupture in the free abdominal cavity, and its presentation
      as an acute abdomen. Large simple liver cysts should be treated with intervention
      at early recognition as conservative management usually results in their
      recurrence.

PMID- 20157431
TI  - Neurolymphomatosis mimicking neurosarcoidosis: a case report.
AB  - INTRODUCTION: Both neurosarcoidosis and central nervous system lymphoma can be
      very difficult to diagnose. We describe the case of a patient in whom
      neurosarcoidosis was strongly suspected, but who was eventually found to have
      lymphoma. We believe the case to be of interest and practical value to
      neurologists, oncologists and internists with an interest in inflammatory
      diseases. CASE PRESENTATION: A diagnosis of neurosarcoidosis was considered in a
      49-year-old Caucasian man on the basis of the following symptoms and indications:
      a cough, bilateral hilar lymphadenopathy confirmed by thoracic computed
      tomography, the development of an S1 radiculopathy, cerebrospinal fluid
      abnormalities (raised protein level), bilateral lung hilar and lachrymal gland
      uptake on a gallium scan, and erythema nodosum confirmed with skin biopsy. These
      were followed by the development of multiple cranial neuropathies, including
      seventh nerve palsy. Exhaustive further investigations yielded no evidence for an
      alternative diagnosis. Treatments with steroids, cyclophosphamide, intravenous
      immunoglobulin and finally infliximab were of no benefit. He eventually developed
      cutaneous nodules, a biopsy of which revealed lymphoma that proved resistant to
      therapy. CONCLUSION: Constant diagnostic vigilance is required in disorders such
      as neurosarcoidosis.

PMID- 20157432
TI  - Anti-inflammatory effects of antidepressant and atypical antipsychotic medication
      for the treatment of major depression and comorbid arthritis: a case report.
AB  - INTRODUCTION: This case report describes the effects of psychotropic treatment,
      quetiapine in particular, on systemic inflammation, pain, general functioning and
      major depression in the treatment of a woman with arthritis. CASE PRESENTATION: A
      49-year-old Caucasian Australian woman with arthritis, pain and depression was
      treated with a course of escitalopram, mirtazapine and quetiapine. Pain levels,
      general functioning and degree of depressive symptoms were evaluated with a
      visual analogue scale. Systemic inflammation had been assessed by C-reactive
      protein serum levels since 2003. C-reactive protein levels, physical pain,
      symptoms of arthritis and depression decreased significantly during the past 12
      months of treatment with quetiapine, while treatment with selective serotonin
      reuptake inhibitors and mirtazapine remained the same. CONCLUSIONS: We suggest
      that the treatment particularly with quetiapine may have anti-inflammatory
      effects in arthritis and comorbid major depression, which eventually led to a
      remission of pain and depression and to normal general function.

PMID- 20157433
TI  - Hepatic involvement in Wegener's granulomatosis: a case report.
AB  - INTRODUCTION: We report the case of a 58-year-old Caucasian Greek man who
      presented with dry cough, fever, bilateral alveolar infiltrates and acute
      hepatitis. CASE PRESENTATION: After a lung biopsy, the patient was diagnosed with
      Wegener's granulomatosis. The diagnosis was supported by the presence of anti
      proteinase-3 anti-neutrophil cytoplasmic antibodies. A liver biopsy demonstrated
      the presence of mild non-specific lobular hepatitis and periodic acid-Schiff
      positive Lafora-like inclusions in a large number of his liver cells. The patient
      was treated with prednisone and cyclophosphamide, which was followed by
      subsequent remissions of chest X-ray findings and liver function studies.
      CONCLUSION: What makes this case worth reporting is the coexistence of liver
      inflammation with a biochemical profile of severe anicteric non-viral, non-drug
      induced hepatitis coinciding with the diagnosis of Wegener's granulomatosis. Our
      paper may be the first report of hepatic involvement in a patient diagnosed with
      Wegener's granulomatosis. The aetiological link between the two diseases is
      supported by the reversion of hepatitis after the immunosuppression of Wegener's
      granulomatosis. We favor the hypothesis that hepatic vasculitis may be the cause
      of acute hepatocellular necrosis.

PMID- 20157434
TI  - Atraumatic patellar prosthesis dislocation with patellar tendon injury following
      a total knee arthroplasty: a case report.
AB  - INTRODUCTION: Total knee arthroplasty is a well-established procedure with
      gratifying results. There is no consensus in the literature whether to routinely
      resurface the patella while performing total knee arthroplasty or not. Although
      an extremely rare occurrence in clinical practice, patellar prosthesis
      dislocation is a possible complication resulting from total knee arthroplasty.
      CASE PRESENTATION: We report a rare case of atraumatic spontaneous dislocation of
      patellar prosthesis in a 63-year-old Caucasian man of British origin with
      patellar tendon injury. The patient was treated successfully through a revision
      of the patellar component and tendon repair. In two years follow-up the patient
      is asymptomatic with no sign of loosening of his patellar prosthesis.
      CONCLUSIONS: A thorough understanding of knee biomechanics is imperative in
      performing total knee arthroplasty in order to achieve a better functional
      outcome and to prevent early prosthetic failure.

PMID- 20157435
TI  - Etanercept and venous thromboembolism: a case series.
AB  - INTRODUCTION: The treatment with antitumor necrosis factor agents has often been
      associated with the induction of autoantibodies (antinuclear antibodies, anti
      double stranded DNA antibodies and antiphospholipid antibodies). The clinical
      significance of these antibodies remains unclear, but they may predispose to
      antiphospholipid syndrome with thromboembolic complications. The association of
      etanercept with thromboembolic events has not been reported previously in the
      literature. CASE PRESENTATION: We describe the cases of three patients with
      rheumatoid arthritis, psoriatic arthritis and seronegative inflammatory arthritis
      who were treated with etanercept. They developed deep vein thrombosis and/or
      pulmonary embolism one to three years after the initiation of etanercept therapy.
      All three patients had a prolonged activated partial thromboplastin time with a
      positive lupus anticoagulant that persisted even after 12 weeks. CONCLUSION:
      Although the clinical significance of antiphospholipid antibodies during
      treatment with antitumor necrosis factor agents remains unclear, they may
      predispose patients to develop antiphospholipid syndrome when associated with
      prolonged activated partial thromboplastin time, lupus anticoagulant positivity,
      or the presence of anti-beta2 glycoprotein I. Clinicians must keep this in mind
      during therapy with antitumor necrosis factor agents in order to prevent, detect
      and treat potential consequences such as deep vein thrombosis and pulmonary
      embolism.

PMID- 20157436
TI  - Riedel's thyroiditis masquerading as anaplastic thyroid carcinoma: a case report.
AB  - INTRODUCTION: Riedel's thyroiditis is a rare thyroid disease characterized by
      dense fibrous tissues that replace the thyroid gland and invade the adjacent
      structures that can mimic thyroid malignancy. We discuss the presentation,
      investigation and management of this very rare condition. CASE PRESENTATION: We
      present a case of a 59-year-old African-Caribbean man who presented with a
      rapidly growing hard neck mass, a hoarse voice, dysphagia and breathing
      difficulty that clinically suggested thyroid malignancy. Biopsy, however,
      revealed dense fibrous tissues suggestive of Riedel's thyroiditis. This was
      successfully treated with very high dose steroids, with no relapse in the
      symptoms. CONCLUSION: It is important for clinicians to be aware of this
      diagnosis when managing patients with thyroid disease, because Riedel's
      thyroiditis can mimic malignancy. In addition, our case demonstrates that this
      condition should be treated with very high dose steroids to prevent relapse.

PMID- 20157437
TI  - Facial skin metastasis of colorectal cancer: a case report.
AB  - INTRODUCTION: Liver and lungs are common locations of distant metastases of
      colorectal cancer. Skin metastases of colorectal cancer are very rare, and facial
      lesions are extremely uncommon. CASE PRESENTATION: An anterior resection of the
      rectum was performed for rectal cancer T3N0M0G3. A small ulcer on the upper lip
      developed 3.5 years after primary operation. Metastasis of adenocarcinoma was
      confirmed histologically, and local excision was performed. At the same time, a
      solitary metastasis in the right lung was diagnosed, and the right lower
      lobectomy was performed. No other metastasis or local recurrences were observed
      during the next 7 months. CONCLUSION: Skin metastases in the face from colorectal
      cancer are very rare and may indicate tumour relapse several years after primary
      resection. These patients have a worse prognosis.

PMID- 20157438
TI  - The value of double balloon enteroscopy in diagnosing blue rubber bleb naevus
      syndrome: a case report.
AB  - Blue rubber bleb naevus syndrome is a rare vascular disorder associated with
      multiple gastrointestinal haemangiomas that have the potential for life
      threatening haemorrhage. These may be difficult to diagnose, and have classically
      been described using computed tomographic studies and/or mesenteric angiography.
      Resected surgical specimens of these lesions, especially in the small bowel, have
      often been extensive and poorly localized. The recent advent and progressive
      development of double balloon enteroscopy has allowed the direct visualization
      and marking of these enteric lesions and serves as a valuable adjunct not only in
      diagnosis but also planning prior to surgery to allow accurate estimate of the
      extent of resection.

PMID- 20157439
TI  - Physical activity levels and determinants of change in young adults: a
      longitudinal panel study.
AB  - BACKGROUND: There is growing concern about physical inactivity in adolescents and
      young adults. Identifying determinants that are associated with low levels of
      physical activity and with changes in physical activity levels will help to
      develop specific prevention strategies. The present study describes the
      prevalence and potential determinants of physical activity behavior and behavior
      changes of young adults. The study is based on the Swiss Household Panel (SHP), a
      longitudinal study assessing social changes in a representative sample of Swiss
      households since 1999. METHODS: Data is collected yearly using computer-assisted
      telephone interviews. Information is obtained from each household member over 14
      years of age. Participants between 14 and 24 years entering the SHP between 1999
      and 2006 were included (N = 3,068). "Inactive" was defined as less than 1
      day/week of at least 30 minutes of moderate physical activity, "no sport" as
      exercising less than once a week. Age, gender, nationality, linguistic region,
      household income, education, membership in a sport club, reading, and Internet
      use were included as potential determinants of physical activity behavior and
      behavior change. RESULTS: In both young men and young women, the prevalence of
      inactivity, "no sport", and non-membership in a sport club was increasing with
      age. Women were less active than men of the same age. From one wave to the
      following, 11.1% of young men and 12.1% of young women became active, and 11.9%
      of men and 13.7% of women became inactive, respectively (pooled data over all
      eight waves). Non-membership in a sport club was the strongest predictor for "no
      sport" (OR(men )6.7 [4.9-8.9]; OR(women )8.1 [5.7-11.4]), but also for being
      inactive (OR 4.6 [3.5-6.0]; 4.6 [3.3-6.4]). Leaving a sport club (OR 7.8 [4.4
      14.0]; 11.9 [5.9-24.1]) and remaining non-member (OR 7.8 [4.7-12.9]; 12.4 [6.4
      24.1]) were the strongest predictors of becoming "no sport". Effects for becoming
      inactive were similar, though smaller (OR 5.9 [3.4-10.5] and 5.1 [2.7-9.6] for
      leaving a club, OR 5.1 [3.1-8.4] and 6.9 [4.0-11.8] for remaining non-member).
      CONCLUSIONS: The most important findings were the strong effects of sport club
      membership on general physical activity. The correlation between sport club
      membership and exercise was not surprising in its nature, but in its strength.

PMID- 20157440
TI  - Physical activity correlates in young women with depressive symptoms: a
      qualitative study.
AB  - BACKGROUND: Young women are at high risk for developing depression and
      participation in physical activity may prevent or treat the disorder. However,
      the influences on physical activity behaviors of young women with depression are
      not well understood. The aim of this study was to gather in-depth information
      about the correlates of physical activity among young women with and without
      depressive symptoms. METHODS: A sample of 40 young women (aged 18-30 years), 20
      with depressive symptoms (assessed using the CES-D 10) and 20 without depressive
      symptoms participated in one-on-one semi-structured interviews. A social
      ecological framework was used, focusing on the individual, social and physical
      environmental influences on physical activity. Thematic analyses were performed
      on transcribed interview data. RESULTS: The results indicated several key themes
      that were unique to women with depressive symptoms. These women more often
      described negative physical activity experiences during their youth, more
      barriers to physical activity, participating in more spontaneous than planned
      activity, lower self-efficacy for physical activity and being influenced by their
      friends' and family's inactivity. CONCLUSIONS: Interventions designed to promote
      physical activity in this important target group should consider strategies to
      reduce/overcome early life negative experiences, engage support from family and
      friends and plan for activity in advance.

PMID- 20157441
TI  - The effect of a motivational intervention on weight loss is moderated by level of
      baseline controlled motivation.
AB  - BACKGROUND: Clinic-based behavioral weight loss programs are effective in
      producing significant weight loss. A one-size-fits-all approach is often taken
      with these programs. It may be beneficial to tailor programs based on
      participants' baseline characteristics. Type and level of motivation may be an
      important factor to consider. Previous research has found that, in general,
      higher levels of controlled motivation are detrimental to behavior change while
      higher levels of autonomous motivation improve the likelihood of behavior
      modification. METHODS: This study assessed the outcomes of two internet
      behavioral weight loss interventions and assessed the effect of baseline
      motivation levels on program success. Eighty females (M (SD) age 48.7 (10.6)
      years; BMI 32.0 (3.7) kg/m(2); 91% Caucasian) were randomized to one of two
      groups, a standard group or a motivation-enhanced group. Both received a 16-week
      internet behavioral weight loss program and attended an initial and a four-week
      group session. Weight and motivation were measured at baseline, four and 16
      weeks. Hierarchical regression analysis was conducted to test for moderation.
      RESULTS: There was significant weight loss at 16-weeks in both groups (p <
      0.001); however there were no between group differences (p = 0.57) (standard
      group 3.4 (3.6) kg; motivation-enhanced group 3.9 (3.4) kg). Further analysis was
      conducted to examine predictors of weight loss. Baseline controlled motivation
      level was negatively correlated with weight loss in the entire sample (r = -0.30;
      p = 0.01). Statistical analysis revealed an interaction between study group
      assignment and baseline level of controlled motivation. Weight loss was not
      predicted by baseline level of controlled motivation in the motivation-enhanced
      group, but was significantly predicted by controlled motivation in the standard
      group. Baseline autonomous motivation did not predict weight change in either
      group. CONCLUSIONS: This research found that, in participants with high levels of
      baseline controlled motivation for weight loss, an intervention designed to
      enhance motivation for weight loss produced significantly greater weight loss
      than a standard behavioral weight loss intervention.

PMID- 20157442
TI  - The relationship between hip abductor muscle strength and iliotibial band
      tightness in individuals with low back pain.
AB  - BACKGROUND: Shortening of the iliotibial band (ITB) has been considered to be
      associated with low back pain (LBP). It is theorized that ITB tightness in
      individuals with LBP is a compensatory mechanism following hip abductor muscle
      weakness. However, no study has clinically examined this theory. The purpose of
      this study was to investigate the muscle imbalance of hip abductor muscle
      weakness and ITB tightness in subjects with LBP. METHODS: A total of 300 subjects
      with and without LBP between the ages of 20 and 60 participated in this cross
      sectional study. Subjects were categorized in three groups: LBP with ITB
      tightness (n = 100), LBP without ITB tightness (n = 100) and no LBP (n = 100).
      Hip abductor muscle strength was measured in all subjects. RESULTS: Analysis of
      Covariance (ANCOVA) with the body mass index (BMI) as the covariate revealed
      significant difference in hip abductor strength between three groups (P < 0.001).
      Post hoc analysis showed no significant difference in hip abductor muscle
      strength between the LBP subjects with and without ITB tightness (P = 0.59).
      However, subjects with no LBP had significantly stronger hip abductor muscle
      strength compared to subjects with LBP with ITB tightness (P < 0.001) and those
      with LBP without ITB tightness (P < 0.001). CONCLUSION: The relationship between
      ITB tightness and hip abductor weakness in patients with LBP is not supported as
      assumed in theory. More clinical studies are needed to assess the theory of
      muscle imbalance of hip abductor weakness and ITB tightness in LBP.

PMID- 20157444
TI  - Spectral distortion in diffuse molecular luminescence tomography in turbid media.
AB  - The influence of tissue optical properties on the shape of near-infrared (NIR)
      fluorescence emission spectra propagating through multiple centimeters of tissue
      like media was investigated. Fluorescence emission spectra measured from 6 cm
      homogeneous tissue-simulating phantoms show dramatic spectral distortion which
      results in emission peak shifts of up to 60 nm in wavelength. Measured spectral
      shapes are highly dependent on the photon path length and the scattered photon
      field in the NIR amplifies the wavelength-dependent absorption of the
      fluorescence spectra. Simulations of the peak propagation using diffusion
      modeling describe the experimental observations and confirm the path length
      dependence of fluorescence emission spectra. Spectral changes are largest for
      long path length measurements and thus will be most important in human tomography
      studies in the NIR. Spectrally resolved detection strategies are required to
      detect and interpret these effects which may otherwise produce erroneous
      intensity measurements. This observed phenomenon is analogous to beam hardening
      in x-ray tomography, which can lead to image artifacts without appropriate
      compensation. The peak shift toward longer wavelengths, and therefore lower
      energy photons, observed for NIR luminescent signals propagating through tissue
      may readily be described as a beam softening phenomenon.

PMID- 20157445
TI  - The effect of viscoelasticity on the stability of a pulmonary airway liquid
      layer.
AB  - The lungs consist of a network of bifurcating airways that are lined with a thin
      liquid film. This film is a bilayer consisting of a mucus layer on top of a
      periciliary fluid layer. Mucus is a non-Newtonian fluid possessing viscoelastic
      characteristics. Surface tension induces flows within the layer, which may cause
      the lung's airways to close due to liquid plug formation if the liquid film is
      sufficiently thick. The stability of the liquid layer is also influenced by the
      viscoelastic nature of the liquid, which is modeled using the Oldroyd-B
      constitutive equation or as a Jeffreys fluid. To examine the role of mucus alone,
      a single layer of a viscoelastic fluid is considered. A system of nonlinear
      evolution equations is derived using lubrication theory for the film thickness
      and the film flow rate. A uniform film is initially perturbed and a normal mode
      analysis is carried out that shows that the growth rate g for a viscoelastic
      layer is larger than for a Newtonian fluid with the same viscosity. Closure
      occurs if the minimum core radius, R(min)(t), reaches zero within one breath.
      Solutions of the nonlinear evolution equations reveal that R(min) normally
      decreases to zero faster with increasing relaxation time parameter, the
      Weissenberg number We. For small values of the dimensionless film thickness
      parameter epsilon, the closure time, t(c), increases slightly with We, while for
      moderate values of epsilon, ranging from 14% to 18% of the tube radius, t(c)
      decreases rapidly with We provided the solvent viscosity is sufficiently small.
      Viscoelasticity was found to have little effect for epsilon>0.18, indicating the
      strong influence of surface tension. The film thickness parameter epsilon and the
      Weissenberg number We also have a significant effect on the maximum shear stress
      on tube wall, max(tau(w)), and thus, potentially, an impact on cell damage.
      Max(tau(w)) increases with epsilon for fixed We, and it decreases with increasing
      We for small We provided the solvent viscosity parameter is sufficiently small.
      For large epsilon approximately 0.2, there is no significant difference between
      the Newtonian flow case and the large We cases.

PMID- 20157443
TI  - The regulation of brain states by neuroactive substances distributed via the
      cerebrospinal fluid; a review.
AB  - The cerebrospinal fluid (CSF) system provides nutrients to and removes waste
      products from the brain. Recent findings suggest, however, that in addition, the
      CSF contains message molecules in the form of actively released neuroactive
      substances. The concentrations of these vary between locations, suggesting they
      are important for the changes in brain activity that underlie different brain
      states, and induce different sensory input and behavioral output
      relationships.The cranial CSF displays a rapid caudally-directed ventricular flow
      followed by a slower rostrally-directed subarachnoid flow (mainly towards the
      cribriform plate and from there into the nasal lymphatics). Thus, many brain
      areas are exposed to and can be influenced by substances contained in the CSF. In
      this review we discuss the production and flow of the CSF, including the
      mechanisms involved in the regulation of its composition. In addition, the
      available evidence for the release of neuropeptides and other neuroactive
      substances into the CSF is reviewed, with particular attention to the selective
      effects of these on distant downstream receptive brain areas. As a conclusion we
      suggest that (1) the flowing CSF is involved in more than just nutrient and waste
      control, but is also used as a broadcasting system consisting of coordinated
      messages to a variety of nearby and distant brain areas; (2) this special form of
      volume transmission underlies changes in behavioral states.

PMID- 20157446
TI  - Gene expression microarray analysis of early oxygen-induced retinopathy in the
      rat.
AB  - Different inbred strains of rat differ in their susceptibility to oxygen-induced
      retinopathy (OIR), an animal model of human retinopathy of prematurity. We
      examined gene expression in Sprague-Dawley (susceptible) and Fischer 344
      (resistant) neonatal rats after 3 days exposure to cyclic hyperoxia or room air,
      using Affymetrix rat Genearrays. False discovery rate analysis was used to
      identify differentially regulated genes. Such genes were then ranked by fold
      change and submitted to the online database, DAVID. The Sprague-Dawley list
      returned the term "response to hypoxia," absent from the Fischer 344 output.
      Manual analysis indicated that many genes known to be upregulated by hypoxia
      inducible factor-1alpha were downregulated by cyclic hyperoxia. Quantitative real
      time RT-PCR analysis of Egln3, Bnip3, Slc16a3, and Hk2 confirmed the microarray
      results. We conclude that combined methodologies are required for adequate
      dissection of the pathophysiology of strain susceptibility to OIR in the rat.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s12177-009-9041-7) contains supplementary material, which is
      available to authorized users.

PMID- 20157447
TI  - Dietary supplements and herbal medicine toxicities-when to anticipate them and
      how to manage them.
AB  - BACKGROUND: Dietary supplements and herbal medicines are gaining popularity in
      many developed countries. AIMS: Although most can be used without any problem,
      serious toxicities do occur. METHODS: Problems can be anticipated when they are
      used for non-traditional indications, at excessive dose, for prolonged duration,
      or by patients who are also on multiple modern pharmaceuticals. Problems should
      also be anticipated when these products claim to be able to relieve symptoms
      rapidly or when herbs with pronounced pharmacological effects or toxic components
      are used. RESULTS: Resuscitation, symptomatic and supportive care are the most
      important aspects of management of toxicities from these products. CONCLUSION:
      This article reviews when problems with these products can be anticipated and
      outlines a practical approach to management.

PMID- 20157448
TI  - Rebuilding the health care system in Afghanistan: an overview of primary care and
      emergency services.
AB  - Developing nations have many challenges to the growth of emergency medical
      systems. This development in Afghanistan is also complicated by many factors that
      plague post-conflict countries including an unstable political system, poor
      economy, poor baseline health indices, and ongoing violence. Progress has been
      made in Afghanistan with the implementation of the Basic Package of Health
      Service (BPHS) by the Ministry of Public Health in an effort to provide
      healthcare that would have the most cost-effective impact on common health
      problems. Trauma and trauma-related disability were both identified as priorities
      under the BPHS, and efforts have begun to address these problems. Most of the
      emergency care delivered in Afghanistan is provided by the military sector and
      non-governmental organizations. Security, lack of infrastructure, economic
      hardship, difficult access to healthcare facilities, poor healthcare facility
      conditions, and lack of trained healthcare providers, especially women, are all
      problems that need to be addressed. The long-term goal of quality healthcare for
      all Afghan citizens will only be met by a combination of specific goal-oriented
      projects, foreign aid, domestic responsibility, and time.

PMID- 20157449
TI  - Correlations between capnographic waveforms and peak flow meter measurement in
      emergency department management of asthma.
AB  - BACKGROUND: The usual method for initial assessment of an acute asthma attack in
      the emergency room includes the use of peak flow measurement and clinical
      parameters. Both methods have their own disadvantages such as poor
      cooperation/effort from patients (peak flow meter) and lack of objective
      assessment (clinical parameters). We were looking into other methods for the
      initial asthma assessment, namely the use of capnography. The normal capnogram
      has an almost square wave pattern comprising phase 1, slope phase 2, plateau
      phase 3, phase 4 and angle alpha (between slopes 2 and 3). The changes in asthma
      include decrease in slope of phase 2, increase in slope 3 and opening of angle
      alpha. AIMS: Our objective was to compare and assess the correlation between the
      changes in capnographic indices and peak flow measurement in non-intubated acute
      asthmatic patients attending the emergency room. METHODS: We carried out a
      prospective study in a university hospital emergency department (ED). One hundred
      and twenty eight patients with acute asthma were monitored with peak flow
      measurements and then had a nasal cannula attached for microstream sampling of
      expired carbon dioxide. The capnographic waveform was recorded onto a PC card for
      indices analysis. The patients were treated according to departmental protocols.
      After treatment, when they were adjudged well for discharge, a second set of
      results was obtained for peak flow measurements and capnographic waveform
      recording. The pre-treatment and post-treatment results were then compared with
      paired samples t-test analysis. Simple and canonical correlations were performed
      to determine correlations between the assessment methods. A p value of below 0.05
      was taken to be significant. RESULTS: Peak flow measurements showed significant
      improvements post-treatment (p < 0.001). On the capnographic waveform, there was
      a significant difference in the slope of phase 3 (p < 0.001) and alpha angle (p <
      0.001), but not in phase 2 slope (p = 0.35). Correlation studies done between the
      assessment methods and indices readings did not show strong correlations either
      between the measurements or the magnitude of change pre-treatment and post
      treatment. CONCLUSION: Peak flow measurements and capnographic waveform indices
      can indicate improvements in airway diameter in acute asthmatics in the ED. Even
      though the two assessment methods did not correlate statistically, capnographic
      waveform analysis presents several advantages in that it is effort independent
      and provides continuous monitoring of normal tidal respiration. They can be
      proposed for the monitoring of asthmatics in the ED.

PMID- 20157450
TI  - Emergency department procedural sedation practice in Cape Town, South Africa.
AB  - BACKGROUND: There are no general policies or protocols for procedural sedation in
      the emergency department and no literature on present practice in South Africa.
      AIMS: To investigate procedural sedation (PS) practice in adults in emergency
      departments (EDs) in Cape Town, South Africa. METHODS: A cross-sectional
      descriptive study was performed by interviewing all ED managers and ED doctors in
      Cape Town meeting the criteria (open 24 h a day, staffed by full-time doctors,
      seeing adult patients and doctors who practice primarily emergency medicine and
      have performed at least one PS in the last 3 months). RESULTS: Data were
      collected from 13 units (5 public, 8 private) and 76 clinicians (48 public, 28
      private). PS facilities are generally good in the private sector, but poor in the
      public sector (lacking in equipment, staff and protocols). Monitoring of patients
      during PS is often substandard, with only two thirds of clinicians using a
      minimum of blood pressure and pulse oximetry monitors during PS. Commonly used
      drugs for PS included midazolam, morphine and propofol (91%, 80% and 28%,
      respectively). Propofol (use of which is increasing in the international ED) is
      more likely to be used by experienced clinicians and those in the private sector.
      Surprisingly, almost half of clinicians would like propofol used on themselves
      hypothetically, although the majority (62%) said they had no or limited knowledge
      of its use and were concerned with its safety. CONCLUSIONS: The private sector is
      generally better serviced for PS than the public sector. Most ED clinicians use
      morphine and midazolam for PS. However, there is widespread awareness of propofol
      as an alternative and probably superior PS drug. Recommendations for improving PS
      include development of general protocols for PS, training of doctors at all
      levels and optimization of ED facilities and staffing.

PMID- 20157451
TI  - Artificial neural network, genetic algorithm, and logistic regression
      applications for predicting renal colic in emergency settings.
AB  - BACKGROUND: Logistic regression is the most common statistical model for
      processing multivariate data in the medical literature. Artificial intelligence
      models like an artificial neural network (ANN) and genetic algorithm (GA) may
      also be useful to interpret medical data. AIMS: The purpose of this study was to
      perform artificial intelligence models on a medical data sheet and compare to
      logistic regression. METHODS: ANN, GA, and logistic regression analysis were
      carried out on a data sheet of a previously published article regarding patients
      presenting to an emergency department with flank pain suspicious for renal colic.
      RESULTS: The study population was composed of 227 patients: 176 patients had a
      diagnosis of urinary stone, while 51 ultimately had no calculus. The GA found two
      decision rules in predicting urinary stones. Rule 1 consisted of being male, pain
      not spreading to back, and no fever. In rule 2, pelvicaliceal dilatation on
      bedside ultrasonography replaced no fever. ANN, GA rule 1, GA rule 2, and
      logistic regression had a sensitivity of 94.9, 67.6, 56.8, and 95.5%, a
      specificity of 78.4, 76.47, 86.3, and 47.1%, a positive likelihood ratio of 4.4,
      2.9, 4.1, and 1.8, and a negative likelihood ratio of 0.06, 0.42, 0.5, and 0.09,
      respectively. The area under the curve was found to be 0.867, 0.720, 0.715, and
      0.713 for all applications, respectively. CONCLUSION: Data mining techniques such
      as ANN and GA can be used for predicting renal colic in emergency settings and to
      constitute clinical decision rules. They may be an alternative to conventional
      multivariate analysis applications used in biostatistics.

PMID- 20157452
TI  - Resident productivity: trends over consecutive shifts.
AB  - BACKGROUND: It has been shown that residents' ability to see more patients and
      patients of higher acuity improves with level of training. AIMS: No published
      study has reviewed whether residents become less productive with consecutive
      shifts. Determining peak resident productivity can optimize staffing to manage
      patient flow and enhance resident exposure to patients, which is critical to
      their education. We examine the relationship between resident productivity and
      number of consecutive shifts worked. METHODS: This is a retrospective review of
      emergency medicine (EM) resident productivity defined as patients evaluated per
      hour per shift. Data were collected utilizing patient tracker software which
      provides a record of physician assignment and checked against the computerized
      medical record. Residents were credited with a patient if they initiated the
      workup and dictated the chart. Productivity was tallied for 188 first-year shift
      strings, 303 second-year shift strings, and 224 third-year shift strings
      beginning 1 November 2006. Analysis of variance (ANOVA) was used to assess for
      productivity differences based on the shift number, with the first shift in a
      series being designated "1," the second consecutive shift being designated "2,"
      and so on. RESULTS: First-year residents saw 0.82, 0.81, and 0.91 patients per
      hour on consecutive shifts (F((2,175))=2.89, p = 0.06), second-year residents saw
      1.12, 1.08, 1.17, and 1.28 patients per hour on consecutive shifts
      (F((3,292))=4.19, p = 0.006), and third-year residents saw 1.19, 1.24, and 1.33
      patients per hour on consecutive shifts (F((2,211))=4.08, p = 0.02). CONCLUSIONS:
      Instead of tiring, residents maintain or improve productivity over consecutive
      shifts.

PMID- 20157453
TI  - Improved care of acute exacerbation of chronic obstructive pulmonary disease in
      two academic emergency departments.
AB  - BACKGROUND: Although several chronic obstructive pulmonary disease (COPD)
      practice guidelines have been published, there is sparse data on the actual
      emergency department (ED) management of acute exacerbation of COPD (AECOPD).
      AIMS: Our objectives were to examine concordance of ED care of AECOPD in older
      patients with guideline recommendations and to evaluate whether concordance has
      improved over time in two academic EDs. METHODS: Data were obtained from two
      cohort studies on AECOPD performed in two academic EDs during two different time
      periods, 2000 and 2005-2006. Both studies included ED patients, aged 55 and
      older, who presented with AECOPD, and cases were confirmed by emergency
      physicians. Data on ED management and disposition were obtained from chart review
      for both cohorts. RESULTS: The analysis included 272 patients: 72 in the 2000
      database and 200 in the 2005-2006 database. The mean age of the patients was 72
      years; 50% were women and 80% white. In 2005-2006, overall concordance with
      guideline recommendations was high (for chest radiography, pulse oximetry,
      bronchodilators, all >/= 90%), except for arterial blood gas testing (7% among
      the admitted) and discharge medication with systemic corticosteroids (42%).
      Compared to the 2000 data, the use of systemic corticosteroids in the ED improved
      from 53 to 77% [absolute improvement: 24%, 95% confidence interval (CI): 11-37%],
      and the use of antibiotics among the patients with respiratory infection symptoms
      improved from 56 to 78% (absolute improvement: 22%, 95% CI: 6-38%). CONCLUSIONS:
      Overall concordance with guideline-recommended care for AECOPD was high in two
      academic EDs, and some emergency treatments have improved over time.

PMID- 20157454
TI  - Comparison of the point-of-care blood gas analyzer versus the laboratory auto
      analyzer for the measurement of electrolytes.
AB  - BACKGROUND: Electrolyte values are measured both by arterial blood gas (ABG)
      analyzers and central laboratory auto-analyzers (AA), but a significant time gap
      exists between the availability of both these results, with the ABG giving faster
      results than the AA. The authors hypothesized that there is no difference between
      the results obtained after measurement of electrolytes by the blood gas and auto
      analyzers. METHODS: After approval by the ethics committee, an observational
      cohort study was conducted in which 200 paired venous and arterial samples from
      patients admitted to the Medical Intensive Care Unit (ICU) of Apollo Hospital,
      Hyderabad, India, were analyzed for electrolytes on the ABG machine and the AA.
      Analyses were done on the ABL555 blood gas analyzer and the Dade Dimension RxL
      Max, both located in the central laboratory. Statistical analyses were performed
      using paired Student's t test. RESULTS: A total of 200 paired samples were
      analyzed. The mean ABG sodium value was 131.28 (SD 7.33), and the mean AA sodium
      value was 136.45 (SD 6.50) (p < 0.001). The mean ABG potassium value was 3.74 (SD
      1.92), and the mean AA potassium value was 3.896 (SD 1.848) (p = 0.2679).
      CONCLUSION: Based on the above analysis, the authors found no significant
      difference between the potassium values measured by the blood gas machine and the
      auto-analyzer. However, the difference between the measured sodium was found to
      be significant. We therefore conclude that critical decisions can be made by
      trusting the potassium values obtained from the arterial blood gas analysis.

PMID- 20157455
TI  - Case of carbon monoxide poisoning after smoking shisha.
AB  - Carbon monoxide poisoning has been reported as a result of exposure to various
      sources of smoke, such as car exhaust fumes, home water heaters and tobacco
      smoke. We describe a case of symptomatic, moderately severe carbon monoxide (CO)
      poisoning in a young Mediterranean man after smoking a waterpipe, or shisha. This
      case highlights the importance of considering carbon monoxide exposure in
      patients presenting with non-specific neurological symptoms to the emergency
      department (ED).

PMID- 20157456
TI  - Portomesenteric air from acute necrotizing appendicitis.

PMID- 20157457
TI  - Listening to syncope.

PMID- 20157458
TI  - Ovarian torsion in a prepubertal girl.

PMID- 20157459
TI  - Post-traumatic pneumocephalus.

PMID- 20157460
TI  - Acute left flank pain.

PMID- 20157461
TI  - Emergency department over-crowding: a global perspective.

PMID- 20157462
TI  - Emergency medicine in Dubai, UAE.
AB  - Dubai has rapidly risen to prominence in the Persian Gulf region as a center of
      global commerce and tourism and as a cultural crossroad between East and West.
      The health-care infrastructure has undergone rapid development. Collaborations
      with academic medical centers now exist to advance clinical care, teaching and
      research. Emergency medicine has also advanced and is undergoing dynamic change.
      Dubai may soon emerge as a regional leader in emergency medicine training and
      practice.

PMID- 20157463
TI  - Analysis of trends in emergency department attendances, hospital admissions and
      medical staffing in a Hong Kong university hospital: 5-year study.
AB  - BACKGROUND: The workload of emergency departments (ED) continually changes in
      response to presentations, overcrowding and availability of expertise and
      investigations. AIMS: To investigate changes in ED presentations and care
      processes, and the relationship of patient demand and ED staff resources to
      waiting times and processing times. METHODS: Retrospective analysis of
      prospectively collected administrative data from January 1999 to April 2005 in an
      emergency department in a university teaching hospital in Hong Kong. All patients
      attending the emergency department during the study period were included. Monthly
      attendance data were retrieved and analysed to determine both qualitative and
      quantitative changes in the patterns of presentation to the ED using
      prospectively gathered data. RESULTS: Total ED attendances decreased by 25%
      during the study with little seasonal variation. The admission rate and the use
      of ambulances increased steadily and significantly. Medical patients are
      increasing proportionately, but trauma patients are decreased in number.
      CONCLUSION: There have been major changes in the patterns of ED attendances and
      ED waiting times over the study period in this teaching hospital ED. Decreasing
      overall ED numbers are offset by an increasingly elderly population and a more
      complex case mix. Reducing clinical staff numbers appears to reduce the ED's
      capacity to provide timely assessments and care and to function as hospital
      gatekeepers. Restoring staff numbers to previous levels may improve the quality
      and timeliness of ED services. It is necessary to refine measures of ED
      complexity and workload to determine appropriate staffing levels in the future.

PMID- 20157464
TI  - Overcrowding is associated with delays in percutaneous coronary intervention for
      acute myocardial infarction.
AB  - BACKGROUND: Recently developed crowding measures, such as the Emergency
      Department (ED) Work Index (EDWIN) score, provide a quantifiable measurement of
      overcrowding in the ED. AIMS: We sought to determine the association between
      overcrowding, measured with the EDWIN score, and the time required to initiate
      percutaneous coronary intervention (PCI) for patients presenting to the ED with
      acute myocardial infarction (AMI). METHODS: We retrospectively reviewed the
      performance improvement (PI) data on all patients presenting to the ED over a 2
      month period with chest pain and whose subsequent ECG showed AMI requiring PCI.
      We recorded the time from patient presentation to the (1) time to first ECG, (2)
      time to patient arrival in the catheterization laboratory, and (3) time to
      catheter balloon inflation. We calculated EDWIN scores using data archived from
      our electronic tracking board and compared the proportion of patients who
      achieved our established ED goal times between patients presenting during low
      crowding (EDWIN < 1.5) and high crowding (EDWIN > or = 1.5) conditions. RESULTS:
      Seventeen patients underwent emergent PCI in the study period. Patients
      presenting to the ED during periods of low crowding had shorter times to balloon
      inflation (median of 84 min, IQR 80 to 93 min) than patients presenting to the ED
      during periods of high crowding (median of 107 min, IQR 94 to 122 min), P =
      0.008. Times to first ECG and to arrival in the catheterization laboratory were
      not significantly different between patients presenting during low and high
      crowding conditions. CONCLUSION: Overcrowding appears to be associated with a
      decreased likelihood of timely treatment for acute AMI in our ED.

PMID- 20157465
TI  - Intraosseous vascular access in adults using the EZ-IO in an emergency
      department.
AB  - BACKGROUND: Intraosseous (IO) access is an alternative to conventional
      intravenous access. AIMS: We evaluate the use of the EZ-IO as an alternative
      vascular access for patients in the emergency department. METHODS: A non
      randomized, prospective, observational study was performed in adults using the EZ
      IO powered drill device. RESULTS: Twenty-four patients were recruited. There were
      35 intraosseous insertions, including 24 tibial and 11 humeral insertions. All EZ
      IO insertions were achieved within 20 s and were successful at the first attempt
      except for one. Of the intraosseous insertions, 88.6% were reported to be easier
      than intravenous cannulation. We found flow rates to be significantly faster
      using a pressure bag. The seniority of operators did not affect the success of
      insertion. Complications included a glove being caught in the drill device and
      extravasation of fluid although they were easily preventable. CONCLUSION: The use
      of the EZ-IO provides a fast, easy and reliable alternative mode of venous
      access, especially in the resuscitation of patients with no venous vascular
      access in the emergency department. Flow rates may be improved by the use of
      pressure bags.

PMID- 20157466
TI  - Racial disparities in health care-emergency department management of minor head
      injury.
AB  - BACKGROUND/AIM: International research has demonstrated disparities in the
      Emergency Department care of patients of certain racial or ethnic backgrounds.
      The management of minor head injuries requires a careful clinical assessment to
      determine the requirement of a CT scan of the head. The aim of this study was to
      determine if there was any disparity, based on race, in the management of minor
      head injury. METHODS: This was a retrospective, structured, medical record review
      of patients presenting to The Townsville Hospital Emergency Department, between
      September 2004 and April 2007, with minor head injury. The main outcome measure
      was whether or not patients received a CT head scan when clinically indicated.
      The Canadian CT Head Rule was considered the standard for clinical indication for
      a CT head scan. Secondary outcome measures included triage category, waiting
      time, level of care provider, disposition and serum ethanol. RESULTS: A total of
      270 patients (73 indigenous and 196 non-indigenous) were enrolled. There was no
      statistically significant difference in ordering CT head scans when clinically
      indicated between indigenous and non-indigenous patients. However, a trend
      indicating that indigenous patients were less likely to receive a CT head scan
      when clinically indicated (OR 0.35; 95% CI = 0.07 to 1.77) was noted. Indigenous
      patients had a mean waiting time of 44.6 min (SD 49.6) compared to non-indigenous
      with 31.1 min (SD 36.4; p = 0.02). CONCLUSION: This study concluded that there
      was no statistically significant disparity based upon race in the management of
      minor head injuries with regard to decision to perform a CT head scan. There is
      some evidence that indigenous patients waited longer to be seen. A multi-centre
      prospective study is necessary to confirm these findings.

PMID- 20157467
TI  - Do echo-enhanced needles improve time to cannulate in a model of short-axis
      ultrasound-guided vascular access for a group of mostly inexperienced ultrasound
      users?
AB  - BACKGROUND: Vascular access is a critical skill for emergency physicians.
      However, it can be unpredictably challenging in some patients. While ultrasound
      guided vascular access has been encouraged in emergency departments, there have
      been few studies evaluating echo-enhanced needles and their usefulness in
      performing vascular access. AIMS: Our purpose was to determine if the use of an
      echo-enhanced needle tip results in faster vascular access times, with fewer
      needle sticks, fewer redirections, and improved needle visualization in
      ultrasound-guided vascular access with the vessel in the short axis. METHODS:
      This is a prospective, randomized, observational study of ultrasound-guided
      vascular access on a vascular phantom comparing an echo-enhanced needle with a
      standard needle. Each participant viewed a teaching video demonstrating typical
      ultrasound-guided vascular access and then attempted ultrasound-guided vascular
      access using both a standard and an echo-enhanced needle with the vessel in the
      short axis. The numbers of needle sticks, redirections, and time to dye flash
      were measured. RESULTS: The 69 participants attempted 69 short-axis ultrasound
      guided vascular cannulations with no difference in time to dye flash between
      needle types: the median time from needle stick to flash was 17.56 s
      [interquartile range (IQR): 12.37-33.15] for the standard needle and 19.22 s
      (IQR: 10.19-31.10) for the echo-enhanced needle. There was no difference between
      needle types for number of needle sticks or redirects. CONCLUSION: Echo-enhanced
      needles did not provide objective performance improvement compared to standard
      needles during ultrasound-guided vascular access with a vascular access model in
      the short axis.

PMID- 20157468
TI  - Pediatric presentation of a large intrathoracic mass.

PMID- 20157469
TI  - A nail gun injury.

PMID- 20157470
TI  - Lethal hemothorax following thoracic dislocated spinal fracture: the usefulness
      of arterial embolization.

PMID- 20157471
TI  - Chest pain in a 12-year-old boy: when is it a harbinger of poor outcome?
AB  - Chest pain is usually a benign presentation in children who present to emergency
      departments (ED) or primary care centers. Unlike adults, where chest pain is
      commonly due to cardiac causes, in children the cause is more likely secondary to
      non-cardiac causes. Here we present a case of a child known to have hyper
      eosinophilic syndrome (HES) who presented with sudden onset of chest pain and had
      a rapidly progressive and fatal outcome in the ED. We discuss the ED approach to
      the child with chest pain and review acute myocardial infarction (AMI) in
      children.

PMID- 20157472
TI  - Rapid HIV testing program implementation: lessons from the emergency department.
AB  - BACKGROUND: The US Centers for Disease Control and Prevention (CDC) guidelines
      and the World Health Organization (WHO) both recommend HIV testing in health-care
      settings. However, neither organization provides prescriptive details regarding
      how these recommendations should be adapted into clinical practice in an
      emergency department. METHODS: We have implemented an HIV-testing program in the
      ED of a major academic medical center within the scope of the Universal Screening
      for HIV Infection in the Emergency Room (USHER) Trial-a randomized clinical trial
      evaluating the feasibility and cost-effectiveness of HIV screening in this
      setting. RESULTS AND CONCLUSION: Drawing on our collective experiences in
      establishing programs domestically and internationally, we offer a practical
      framework of lessons learned so that others poised to embark on such HIV testing
      programs may benefit from our experiences.

PMID- 20157473
TI  - A posterior epidural mass causing paraparesis in a 20-year-old healthy
      individual.
AB  - We present a case of a posterior epidural abscess at the thoracic vertebral level
      causing paraparesia in a young, healthy individual with no otherwise predisposing
      factors, with normal laboratory findings, as diagnosed using fat-suppressed MR
      imaging. Spinal epidural abscess is a rare condition, encountered mostly in the
      midthoracic or lower lumbar vertebral levels of elderly patients, that has a high
      mortality and morbidity (18-31%) when diagnosis and treatment is delayed. It is
      rarely spontaneous and is usually accompanied by spinal osteomyelitis. Diagnosis
      is rather easy in cases of vertebral osteomyelitis or when classical clinical,
      laboratory and imaging findings are present. However, cases of spontaneous
      development, with no predisposing factors, and lack of abscess suggesting
      clinical and laboratory findings may be a diagnostic challenge. In such cases,
      other posterior epidural masses such as schwannoma, neurofibroma, meningioma and
      hematoma should be considered in the differential diagnosis. Both the clinician
      and the radiology physician should have a high suspicion of epidural abscesses,
      because their early diagnosis and treatment is important. In addition to routine
      MR images, fat-suppressed MR images prove helpful in the diagnosis of spontaneous
      epidural abscesses by showing the inflammatory changes in the paraspinal area.

PMID- 20157474
TI  - New mutant phenotype data curation system in the Saccharomyces Genome Database.
AB  - The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) organizes
      and displays molecular and genetic information about the genes and proteins of
      baker's yeast, Saccharomyces cerevisiae. Mutant phenotype screens have been the
      starting point for a large proportion of yeast molecular biological studies, and
      are still used today to elucidate the functions of uncharacterized genes and
      discover new roles for previously studied genes. To greatly facilitate searching
      and comparison of mutant phenotypes across genes, we have devised a new
      controlled-vocabulary system for capturing phenotype information. Each phenotype
      annotation is represented as an 'observable', which is the entity, or process
      that is observed, and a 'qualifier' that describes the change in that entity or
      process in the mutant (e.g. decreased, increased, or abnormal). Additional
      information about the mutant, such as strain background, allele name, conditions
      under which the phenotype is observed, or the identity of relevant chemicals, is
      captured in separate fields. For each gene, a summary of the mutant phenotype
      information is displayed on the Locus Summary page, and the complete information
      is displayed in tabular format on the Phenotype Details Page. All of the
      information is searchable and may also be downloaded in bulk using SGD's Batch
      Download Tool or Download Data Files Page. In the future, phenotypes will be
      integrated with other curated data to allow searching across different types of
      functional information, such as genetic and physical interaction data and Gene
      Ontology annotations.Database URL:http://www.yeastgenome.org/

PMID- 20157475
TI  - DATABASE: A new forum for biological databases and curation.

PMID- 20157476
TI  - Analysis of CASP8 targets, predictions and assessment methods.
AB  - Results of the recent Critical Assessment of Techniques for Protein Structure
      Prediction, CASP8, present several valuable sources of information. First, CASP
      targets comprise a realistic sample of currently solved protein structures and
      exemplify the corresponding challenges for predictors. Second, the plethora of
      predictions by all possible methods provides an unusually rich material for
      evolutionary analysis of target proteins. Third, CASP results show the current
      state of the field and highlight specific problems in both predicting and
      assessing. Finally, these data can serve as grounds to develop and analyze
      methods for assessing prediction quality. Here we present results of our analysis
      in these areas. Our objective is not to duplicate CASP assessment, but to use our
      unique experience as former CASP5 assessors and CASP8 predictors to (i) offer
      more insights into CASP targets and predictions based on expert analysis,
      including invaluable analysis prior to target structure release; and (ii) develop
      an assessment methodology tailored towards current challenges in the field.
      Specifically, we discuss preparing target structures for assessment, parsing
      protein domains, balancing evaluations based on domains and on whole chains,
      dividing targets into categories and developing new evaluation scores. We also
      present evolutionary analysis of the most interesting and challenging
      targets.Database URL: Our results are available as a comprehensive database of
      targets and predictions at http://prodata.swmed.edu/CASP8.

PMID- 20157477
TI  - The Homeodomain Resource: a comprehensive collection of sequence, structure,
      interaction, genomic and functional information on the homeodomain protein
      family.
AB  - The Homeodomain Resource is a curated collection of sequence, structure,
      interaction, genomic and functional information on the homeodomain family. The
      current version builds upon previous versions by the addition of new, complete
      sets of homeodomain sequences from fully sequenced genomes, the expansion of
      existing curated homeodomain information and the improvement of data
      accessibility through better search tools and more complete data integration.
      This release contains 1534 full-length homeodomain-containing sequences, 93
      experimentally derived homeodomain structures, 101 homeodomain protein-protein
      interactions, 107 homeodomain DNA-binding sites and 206 homeodomain proteins
      implicated in human genetic disorders.Database URL: The Homeodomain Resource is
      freely available and can be accessed at
      http://research.nhgri.nih.gov/homeodomain/

PMID- 20157478
TI  - Gramene QTL database: development, content and applications.
AB  - Gramene is a comparative information resource for plants that integrates data
      across diverse data domains. In this article, we describe the development of a
      quantitative trait loci (QTL) database and illustrate how it can be used to
      facilitate both the forward and reverse genetics research. The QTL database
      contains the largest online collection of rice QTL data in the world. Using
      flanking markers as anchors, QTLs originally reported on individual genetic maps
      have been systematically aligned to the rice sequence where they can be searched
      as standard genomic features. Researchers can determine whether a QTL co
      localizes with other QTLs detected in independent experiments and can combine
      data from multiple studies to improve the resolution of a QTL position. Candidate
      genes falling within a QTL interval can be identified and their relationship to
      particular phenotypes can be inferred based on functional annotations provided by
      ontology terms. Mutations identified in functional genomics populations and
      association mapping panels can be aligned with QTL regions to facilitate fine
      mapping and validation of gene-phenotype associations. By assembling and
      integrating diverse types of data and information across species and levels of
      biological complexity, the QTL database enhances the potential to understand and
      utilize QTL information in biological research.

PMID- 20157479
TI  - DBH2H: vertebrate head-to-head gene pairs annotated at genomic and post-genomic
      levels.
AB  - DBH2H collects head-to-head (h2h) gene pairs identified from human, mouse, rat,
      chicken and fugu genomes, and distinguishes the ortholog mapping relationship
      among them. The gene pairs in DBH2H are annotated with sequential features
      including single nucleotide polymorphisms, CpG islands and transcription factor
      binding sites, as well as functional terms and genetic disorders. In addition,
      the expression correlation information based on 117 microarray datasets is
      included. By providing user-friendly access to these data, DBH2H represents a
      valuable resource for further analyses of this important gene arrangement in
      terms of transcriptional regulation mechanisms, evolutionary conservation,
      disease relevance, etc.Database URL:http://lifecenter.sgst.cn/h2h/

PMID- 20157480
TI  - Radiation Genes: a database devoted to microarrays screenings revealing
      transcriptome alterations induced by ionizing radiation in mammalian cells.
AB  - The analysis of the great extent of data generated by using DNA microarrays
      technologies has shown that the transcriptional response to radiation can be
      considerably different depending on the quality, the dose range and dose rate of
      radiation, as well as the timing selected for the analysis. At present, it is
      very difficult to integrate data obtained under several experimental conditions
      in different biological systems to reach overall conclusions or build regulatory
      models which may be tested and validated. In fact, most available data is buried
      in different websites, public or private, in general or local repositories or in
      files included in published papers; it is often in various formats, which makes a
      wide comparison even more difficult. The Radiation Genes Database
      (http://www.caspur.it/RadiationGenes) collects microarrays data from various
      local and public repositories or from published papers and supplementary
      materials. The database classifies it in terms of significant variables, such as
      radiation quality, dose, dose rate and sampling timing, as to provide user
      friendly tools to facilitate data integration and comparison.

PMID- 20157481
TI  - miRo: a miRNA knowledge base.
AB  - miRo is a web-based knowledge base that provides users with miRNA-phenotype
      associations in humans. It integrates data from various online sources, such as
      databases of miRNAs, ontologies, diseases and targets, into a unified database
      equipped with an intuitive and flexible query interface and data mining
      facilities. The main goal of miRo is the establishment of a knowledge base which
      allows non-trivial analysis through sophisticated mining techniques and the
      introduction of a new layer of associations between genes and phenotypes inferred
      based on miRNAs annotations. Furthermore, a specificity function applied to
      validated data highlights the most significant associations. The miRo web site is
      available at: http://ferrolab.dmi.unict.it/miro.Database
      URL:http://ferrolab.dmi.unict.it/miro.

PMID- 20157482
TI  - Dr. Zompo: an online data repository for Zostera marina and Posidonia oceanica
      ESTs.
AB  - As ecosystem engineers, seagrasses are angiosperms of paramount ecological
      importance in shallow shoreline habitats around the globe. Furthermore, the
      ancestors of independent seagrass lineages have secondarily returned into the sea
      in separate, independent evolutionary events. Thus, understanding the molecular
      adaptation of this clade not only makes significant contributions to the field of
      ecology, but also to principles of parallel evolution as well. With the use of
      Dr. Zompo, the first interactive seagrass sequence database presented here, new
      insights into the molecular adaptation of marine environments can be inferred.
      The database is based on a total of 14 597 ESTs obtained from two seagrass
      species, Zostera marina and Posidonia oceanica, which have been processed,
      assembled and comprehensively annotated. Dr. Zompo provides experimentalists with
      a broad foundation to build experiments and consider challenges associated with
      the investigation of this class of non-domesticated monocotyledon systems. Our
      database, based on the Ruby on Rails framework, is rich in features including the
      retrieval of experimentally determined heat-responsive transcripts, mining for
      molecular markers (SSRs and SNPs), and weighted key word searches that allow
      access to annotation gathered on several levels including Pfam domains,
      GeneOntology and KEGG pathways. Well established plant genome sites such as The
      Arabidopsis Information Resource (TAIR) and the Rice Genome Annotation Project
      are interfaced by Dr. Zompo. With this project, we have initialized a valuable
      resource for plant biologists in general and the seagrass community in
      particular. The database is expected to grow together with more data to come in
      the near future, particularly with the recent initiation of the Zostera genome
      sequencing project.The Dr. Zompo database is available at http://drzompo.uni
      muenster.de/

PMID- 20157483
TI  - QuickGO: a user tutorial for the web-based Gene Ontology browser.
AB  - The Gene Ontology (GO) has proven to be a valuable resource for functional
      annotation of gene products. At well over 27 000 terms, the descriptiveness of GO
      has increased rapidly in line with the biological data it represents. Therefore,
      it is vital to be able to easily and quickly mine the functional information that
      has been made available through these GO terms being associated with gene
      products. QuickGO is a fast, web-based tool for browsing the GO and all
      associated GO annotations provided by the GOA group. After undergoing a
      redevelopment, QuickGO is now able to offer many more features beyond simple
      browsing. Users have responded well to the new tool and given very positive
      feedback about its usefulness. This tutorial will demonstrate how some of these
      features could be useful to the researcher wanting to discover more about their
      dataset, particular areas of biology or to find new ways of directing their
      research.Database URL:http://www.ebi.ac.uk/QuickGO.

PMID- 20157484
TI  - The Prion Disease Database: a comprehensive transcriptome resource for systems
      biology research in prion diseases.
AB  - Prion diseases reflect conformational conversion of benign isoforms of prion
      protein (PrP(C)) to malignant PrP(Sc) isoforms. Networks perturbed by PrP(Sc)
      accumulation and their ties to pathological events are poorly understood. Time
      course transcriptomic and phenotypic data in animal models are critical for
      understanding prion-perturbed networks in systems biology studies. Here, we
      present the Prion Disease Database (PDDB), the most comprehensive data resource
      on mouse prion diseases to date. The PDDB contains: (i) time-course mRNA
      measurements spanning the interval from prion inoculation through appearance of
      clinical signs in eight mouse strain-prion strain combinations and (ii)
      histoblots showing temporal PrP(Sc) accumulation patterns in brains from each
      mouse-prion combination. To facilitate prion research, the PDDB also provides a
      suite of analytical tools for reconstructing dynamic networks via integration of
      temporal mRNA and interaction data and for analyzing these networks to generate
      hypotheses.Database URL:http://prion.systemsbiology.net.

PMID- 20157485
TI  - A community-curated consensual annotation that is continuously updated: the
      Bacillus subtilis centred wiki SubtiWiki.
AB  - Bacillus subtilis is the model organism for Gram-positive bacteria, with a large
      amount of publications on all aspects of its biology. To facilitate genome
      annotation and the collection of comprehensive information on B. subtilis, we
      created SubtiWiki as a community-oriented annotation tool for information
      retrieval and continuous maintenance. The wiki is focused on the needs and
      requirements of scientists doing experimental work. This has implications for the
      design of the interface and for the layout of the individual pages. The pages can
      be accessed primarily by the gene designations. All pages have a similar flexible
      structure and provide links to related gene pages in SubtiWiki or to information
      in the World Wide Web. Each page gives comprehensive information on the gene, the
      encoded protein or RNA as well as information related to the current
      investigation of the gene/protein. The wiki has been seeded with information from
      key publications and from the most relevant general and B. subtilis-specific
      databases. We think that SubtiWiki might serve as an example for other scientific
      wikis that are devoted to the genes and proteins of one organism.Database URL:
      The wiki can be accessed at http://subtiwiki.uni-goettingen.de/

PMID- 20157486
TI  - Differential direct coding: a compression algorithm for nucleotide sequence data.
AB  - While modern hardware can provide vast amounts of inexpensive storage for
      biological databases, the compression of nucleotide sequence data is still of
      paramount importance in order to facilitate fast search and retrieval operations
      through a reduction in disk traffic. This issue becomes even more important in
      light of the recent increase of very large data sets, such as metagenomes. In
      this article, I propose the Differential Direct Coding algorithm, a general
      purpose nucleotide compression protocol that can differentiate between sequence
      data and auxiliary data by supporting the inclusion of supplementary symbols that
      are not members of the set of expected nucleotide bases, thereby offering
      reconciliation between sequence-specific and general-purpose compression
      strategies. This algorithm permits a sequence to contain a rich lexicon of
      auxiliary symbols that can represent wildcards, annotation data and special
      subsequences, such as functional domains or special repeats. In particular, the
      representation of special subsequences can be incorporated to provide structure
      based coding that increases the overall degree of compression. Moreover,
      supporting a robust set of symbols removes the requirement of wildcard
      elimination and restoration phases, resulting in a complexity of O(n) for
      execution time, making this algorithm suitable for very large data sets. Because
      this algorithm compresses data on the basis of triplets, it is highly amenable to
      interpretation as a polypeptide at decompression time. Also, an encoded sequence
      may be further compressed using other existing algorithms, like gzip, thereby
      maximizing the final degree of compression. Overall, the Differential Direct
      Coding algorithm can offer a beneficial impact on disk traffic for database
      queries and other disk-intensive operations.

PMID- 20157487
TI  - ORION-VIRCAT: a tool for mapping ICTV and NCBI taxonomies.
AB  - Viruses, viroids and prions are the smallest infectious biological entities that
      depend on their host for replication. The number of pathogenic viruses is
      considerably large and their impact in human global health is well documented.
      Currently, the International Committee on the Taxonomy of Viruses (ICTV) has
      classified approximately 4379 virus species while the National Center for
      Biotechnology Information Viral Genomes Resource (NCBI-VGR) database has mapped
      617 705 proteins to eight large taxonomic groups. Despite these efforts, an
      automated approach for mapping the ICTV master list and its officially accepted
      virus naming to the NCBI-VGR's taxonomical classification is not available. Due
      to metagenomic sequencing, it is likely that the discovery and naming of new
      viral species will increase by at least ten fold. Unfortunately, existing viral
      databases are not adequately prepared to scale, maintain and annotate
      automatically ultra-high throughput sequences and place this information into
      specific taxonomic categories. ORION-VIRCAT is a scalable and interoperable
      object-relational database designed to serve as a resource for the integration
      and verification of taxonomical classifications generated by the ICTV and NCBI
      VGR. The current release (v1.0) of ORION-VIRCAT is implemented in PostgreSQL and
      it has been extended to ORACLE, MySQL and SyBase. ORION-VIRCAT automatically
      mapped and joined 617 705 entries from the NCBI-VGR to the viral naming of the
      ICTV. This detailed analysis revealed that 399 095 entries from the NCBI-VGR can
      be mapped to the ICTV classification and that one Order, 10 families, 35 genera
      and 503 species listed in the ICTV disagree with the the NCBI-VGR classification
      schema. Nevertheless, we were eable to correct several discrepancies mapping 234
      000 additional entries.Database
      URL:http://www.orionbiosciences.com/research/orion-vircat.html.

PMID- 20157488
TI  - A large and accurate collection of peptidase cleavages in the MEROPS database.
AB  - Peptidases are enzymes that hydrolyse peptide bonds in proteins and peptides.
      Peptidases are important in pathological conditions such as Alzheimer's disease,
      tumour and parasite invasion, and for processing viral polyproteins. The MEROPS
      database is an Internet resource containing information on peptidases, their
      substrates and inhibitors. The database now includes details of cleavage
      positions in substrates, both physiological and non-physiological, natural and
      synthetic. There are 39 118 cleavages in the collection; including 34 606 from a
      total of 10 513 different proteins and 2677 cleavages in synthetic substrates.
      The number of cleavages designated as 'physiological' is 13 307. The data are
      derived from 6095 publications. At least one substrate cleavage is known for 45%
      of the 2415 different peptidases recognized in the MEROPS database. The website
      now has three new displays: two showing peptidase specificity as a logo and a
      frequency matrix, the third showing a dynamically generated alignment between
      each protein substrate and its most closely related homologues. Many of the
      proteins described in the literature as peptidase substrates have been studied
      only in vitro. On the assumption that a physiologically relevant cleavage site
      would be conserved between species, the conservation of every site in terms of
      peptidase preference has been examined and a number have been identified that are
      not conserved. There are a number of cogent reasons why a site might not be
      conserved. Each poorly conserved site has been examined and a reason postulated.
      Some sites are identified that are very poorly conserved where cleavage is more
      likely to be fortuitous than of physiological relevance. This data-set is freely
      available via the Internet and is a useful training set for algorithms to predict
      substrates for peptidases and cleavage positions within those substrates. The
      data may also be useful for the design of inhibitors and for engineering novel
      specificities into peptidases.Database URL:http://merops.sanger.ac.uk.

PMID- 20157489
TI  - Collaborative annotation of genes and proteins between UniProtKB/Swiss-Prot and
      dictyBase.
AB  - UniProtKB/Swiss-Prot, a curated protein database, and dictyBase, the Model
      Organism Database for Dictyostelium discoideum, have established a collaboration
      to improve data sharing. One of the major steps in this effort was the 'Dicty
      annotation marathon', a week-long exercise with 30 annotators aimed at achieving
      a major increase in the number of D. discoideum proteins represented in
      UniProtKB/Swiss-Prot. The marathon led to the annotation of over 1000 D.
      discoideum proteins in UniProtKB/Swiss-Prot. Concomitantly, there were a large
      number of updates in dictyBase concerning gene symbols, protein names and gene
      models. This exercise demonstrates how UniProtKB/Swiss-Prot can work in very
      close cooperation with model organism databases and how the annotation of
      proteins can be accelerated through those collaborations.

PMID- 20157490
TI  - Models for financial sustainability of biological databases and resources.
AB  - Following the technological advances that have enabled genome-wide analysis in
      most model organisms over the last decade, there has been unprecedented growth in
      genomic and post-genomic science with concomitant generation of an exponentially
      increasing volume of data and material resources. As a result, numerous
      repositories have been created to store and archive data, organisms and material,
      which are of substantial value to the whole community. Sustained access,
      facilitating re-use of these resources, is essential, not only for validation,
      but for re-analysis, testing of new hypotheses and developing new
      technologies/platforms. A common challenge for most data resources and biological
      repositories today is finding financial support for maintenance and development
      to best serve the scientific community. In this study we examine the problems
      that currently confront the data and resource infrastructure underlying the
      biomedical sciences. We discuss the financial sustainability issues and potential
      business models that could be adopted by biological resources and consider long
      term preservation issues within the context of mouse functional genomics efforts
      in Europe.

PMID- 20157491
TI  - Understanding PubMed user search behavior through log analysis.
AB  - This article reports on a detailed investigation of PubMed users' needs and
      behavior as a step toward improving biomedical information retrieval. PubMed is
      providing free service to researchers with access to more than 19 million
      citations for biomedical articles from MEDLINE and life science journals. It is
      accessed by millions of users each day. Efficient search tools are crucial for
      biomedical researchers to keep abreast of the biomedical literature relating to
      their own research. This study provides insight into PubMed users' needs and
      their behavior. This investigation was conducted through the analysis of one
      month of log data, consisting of more than 23 million user sessions and more than
      58 million user queries. Multiple aspects of users' interactions with PubMed are
      characterized in detail with evidence from these logs. Despite having many
      features in common with general Web searches, biomedical information searches
      have unique characteristics that are made evident in this study. PubMed users are
      more persistent in seeking information and they reformulate queries often. The
      three most frequent types of search are search by author name, search by
      gene/protein, and search by disease. Use of abbreviation in queries is very
      frequent. Factors such as result set size influence users' decisions. Analysis of
      characteristics such as these plays a critical role in identifying users'
      information needs and their search habits. In turn, such an analysis also
      provides useful insight for improving biomedical information retrieval.Database
      URL:http://www.ncbi.nlm.nih.gov/PubMed.

PMID- 20157492
TI  - Integrating text mining into the MGI biocuration workflow.
AB  - A major challenge for functional and comparative genomics resource development is
      the extraction of data from the biomedical literature. Although text mining for
      biological data is an active research field, few applications have been
      integrated into production literature curation systems such as those of the model
      organism databases (MODs). Not only are most available biological natural
      language (bioNLP) and information retrieval and extraction solutions difficult to
      adapt to existing MOD curation workflows, but many also have high error rates or
      are unable to process documents available in those formats preferred by
      scientific journals.In September 2008, Mouse Genome Informatics (MGI) at The
      Jackson Laboratory initiated a search for dictionary-based text mining tools that
      we could integrate into our biocuration workflow. MGI has rigorous document
      triage and annotation procedures designed to identify appropriate articles about
      mouse genetics and genome biology. We currently screen approximately 1000 journal
      articles a month for Gene Ontology terms, gene mapping, gene expression,
      phenotype data and other key biological information. Although we do not foresee
      that curation tasks will ever be fully automated, we are eager to implement named
      entity recognition (NER) tools for gene tagging that can help streamline our
      curation workflow and simplify gene indexing tasks within the MGI system. Gene
      indexing is an MGI-specific curation function that involves identifying which
      mouse genes are being studied in an article, then associating the appropriate
      gene symbols with the article reference number in the MGI database.Here, we
      discuss our search process, performance metrics and success criteria, and how we
      identified a short list of potential text mining tools for further evaluation. We
      provide an overview of our pilot projects with NCBO's Open Biomedical Annotator
      and Fraunhofer SCAI's ProMiner. In doing so, we prove the potential for the
      further incorporation of semi-automated processes into the curation of the
      biomedical literature.

PMID- 20157493
TI  - MicroScope: a platform for microbial genome annotation and comparative genomics.
AB  - The initial outcome of genome sequencing is the creation of long text strings
      written in a four letter alphabet. The role of in silico sequence analysis is to
      assist biologists in the act of associating biological knowledge with these
      sequences, allowing investigators to make inferences and predictions that can be
      tested experimentally. A wide variety of software is available to the scientific
      community, and can be used to identify genomic objects, before predicting their
      biological functions. However, only a limited number of biologically interesting
      features can be revealed from an isolated sequence. Comparative genomics tools,
      on the other hand, by bringing together the information contained in numerous
      genomes simultaneously, allow annotators to make inferences based on the idea
      that evolution and natural selection are central to the definition of all
      biological processes. We have developed the MicroScope platform in order to offer
      a web-based framework for the systematic and efficient revision of microbial
      genome annotation and comparative analysis
      (http://www.genoscope.cns.fr/agc/microscope). Starting with the description of
      the flow chart of the annotation processes implemented in the MicroScope
      pipeline, and the development of traditional and novel microbial annotation and
      comparative analysis tools, this article emphasizes the essential role of expert
      annotation as a complement of automatic annotation. Several examples illustrate
      the use of implemented tools for the review and curation of annotations of both
      new and publicly available microbial genomes within MicroScope's rich integrated
      genome framework. The platform is used as a viewer in order to browse updated
      annotation information of available microbial genomes (more than 440 organisms to
      date), and in the context of new annotation projects (117 bacterial genomes). The
      human expertise gathered in the MicroScope database (about 280,000 independent
      annotations) contributes to improve the quality of microbial genome annotation,
      especially for genomes initially analyzed by automatic procedures alone.Database
      URLs: http://www.genoscope.cns.fr/agc/mage and
      http://www.genoscope.cns.fr/agc/microcyc.

PMID- 20157494
TI  - Whole-organ pancreas transplantation at Baylor Regional Transplant Institute: a
      chance to cure diabetes.
AB  - The success of pancreas transplantation has improved over the past several
      decades with advancements in surgical technique, immunosuppressive medicines, and
      immunologic testing. We retrospectively reviewed our experience with pancreas
      transplantation from 1995 to 2008. At the Baylor Regional Transplant Program, 151
      pancreas transplants were performed in 147 patients: 135 were simultaneous
      pancreas-kidney transplants, 10 were pancreas transplants after kidney
      transplants, and 6 were pancreas transplants alone. Follow-up information was
      available for 138 patients. The 1-year acute cellular rejection rate was 31.6%;
      the 30-day surgical reexploration rate was 10%; and the technical failure rate
      was 5.3%. Five-year pancreas graft survival rates were 67% for simultaneous
      pancreas and kidney transplants and 50% for pancreas transplants after kidney
      transplants. These outcomes exceed expected results as calculated by the
      Scientific Registry of Transplant Recipients. In addition, the median time to
      transplant was 3.8 months, compared with a US median of 14.1 months. Pancreas
      transplantation is currently the closest thing to a cure for diabetes and should
      be given as an option for diabetic patients with or without end-stage renal
      disease.

PMID- 20157495
TI  - Measurement of functional capacity requirements of police officers to aid in
      development of an occupation-specific cardiac rehabilitation training program.
AB  - This study was designed to measure the functional capacity of healthy subjects
      during strenuous simulated police tasks, with the goal of developing occupation
      specific training for cardiac rehabilitation of police officers. A calibrated
      metabolic instrument and an oxygen consumption data collection mask were used to
      measure the oxygen consumption and heart rates of 30 Dallas Police Academy
      officers and cadets as they completed an 8-event obstacle course that simulated
      chasing, subduing, and handcuffing a suspect. Standard target heart rates (85% of
      age-predicted maximum heart rate, or 0.85 x [220 - age]) and metabolic
      equivalents (METs) were calculated; a matched-sample t test based on differences
      between target and achieved heart rate and MET level was used for statistical
      analysis. Peak heart rates during the obstacle course simulation were
      significantly higher than the standard target heart rates (those at which
      treadmill stress tests in physicians' offices are typically stopped) (t(29) =
      12.81, P < 0.001) and significantly higher than the suggested maximum of 150
      beats/min during cardiac rehabilitation training (t(29) = 17.84, P < 0.001). Peak
      MET levels during the obstacle course simulation were also significantly higher
      than the goal level (8 METs) that patients typically achieve in a cardiac
      rehabilitation program (t(29) = 14.73, P < 0.001). We conclude that police work
      requires a functional capacity greater than that typically attained in
      traditional cardiac rehabilitation programs. Rehabilitation professionals should
      consider performing maximal stress tests and increasing the intensity of cardiac
      rehabilitation workouts to effectively train police officers who have had a
      cardiac event.

PMID- 20157496
TI  - Circulating tumor cells in patients undergoing surgery for hepatic metastases
      from colorectal cancer.
AB  - Circulating tumor cells (CTCs) have been detected in patients with a variety of
      metastatic cancers, including colorectal, and may be a significant prognostic
      variable in patients with liver metastases. This prospective study involved 20
      patients (13 men and 7 women) undergoing surgical excision or ablation of liver
      metastases from a colon or rectal primary tumor. Four 7.5-mL vials of peripheral
      blood were drawn preoperatively, 2 weeks postoperatively, and during mobilization
      of the liver or at the beginning of radiofrequency ablation. The samples were
      centrifuged, the sera combined to a final volume of 7.5 mL, and the CellSearch
      system used to identify circulating epithelial cells. A CTC count >2 was defined
      as clinically significant. Preoperative CTC levels averaged 3.9 (range, 0-56) and
      were significant in 2 patients (10%). Postoperative CTC levels averaged 1.0 (in
      18 patients; range, 0-9) and were significant in 1 patient (5%). Intraoperative
      CTC levels averaged 28.2 (range, 0-315) and were significant in 10 patients
      (50%). At a median follow-up of 11.5 months (range, 5-25), 6 patients (30%) were
      dead of disease, 6 patients (30%) showed no evidence of disease, and 8 patients
      (40%) were alive with disease. Statistical analysis suggested a correlation
      between the presence of postoperative CTCs and survival (P = 0.036), as well as
      with disease-free survival (P = 0.036). Thus, CTCs are present and quantifiable
      in many patients with colorectal hepatic metastases, and peripheral CTCs are
      present in greater quantity during intraoperative liver manipulation. This
      preliminary study suggests a relationship between the presence of postoperative
      CTCs and outcome. Further accrual and follow-up of this group is needed to
      confirm these findings.

PMID- 20157497
TI  - Sensitivity and specificity of frequently used electrocardiographic criteria for
      left ventricular hypertrophy in patients with anterior wall myocardial
      infarction.
AB  - Electrocardiographic left ventricular hypertrophy (LVH) strongly predicts
      mortality in patients with myocardial infarction (MI). However, the validity of
      LVH voltage criteria in this context has not been assessed. Reviewing the coded
      database of echocardiographic studies performed at one institution, we performed
      a retrospective analysis of 49 patients who had anterior akinesis on the
      echocardiogram and anterior wall MI on the electrocardiogram. Results showed
      that, compared with the sensitivities and specificities of the
      electrocardiographic voltage criteria in historical cohorts, Cornell criteria
      were less sensitive and specific for the diagnosis of LVH in patients with
      anterior wall MI. The sensitivity was reduced in the presence of an associated
      lateral wall MI, and the specificity was reduced in the absence of a lateral wall
      MI (overall sensitivity in case of anterior wall MI, with or without an
      associated lateral wall MI, 21% vs 41%, P = 0.049; overall specificity 84% vs
      98%, P = 0.003). All criteria, except for S in V(1) + R in V(5) or V(6) >3.5 mV,
      had a significantly reduced specificity in the case of anterior wall MI not
      associated with lateral wall MI, and all criteria, except for R in V(6) > R in
      V(5), had reduced sensitivity in the presence of a lateral wall MI. In
      conclusion, anterior wall MI reduces the sensitivity and the specificity of the
      most commonly used LVH voltage criteria.

PMID- 20157498
TI  - 5-Oxoproline (pyroglutamic) acidosis associated with chronic acetaminophen use.

PMID- 20157499
TI  - Congenital pulmonic stenosis in a 77-year-old woman successfully treated with
      percutaneous balloon valvuloplasty.
AB  - Congenital pulmonic stenosis (PS) rarely presents in patients over the age of 55
      years. A stable asymptomatic course into late adulthood is the usual history of
      mild to moderate PS. Balloon valvuloplasty has become the procedure of choice for
      congenital PS, especially in children and young adults. There are rare reports of
      its use in older adults. Significant valve calcium is believed to limit its
      success. We present a case of a 77-year-old woman with symptomatic congenital PS
      and severe valve calcium who underwent successful balloon valvuloplasty.

PMID- 20157500
TI  - Endovascular management of suprascapular artery pseudoaneurysm.
AB  - Pseudoaneurysms can be debilitating for patients and occasionally life
      threatening. Many imaging modalities may be used to assess and define these
      vascular lesions, and various methods have been employed in their treatment. Our
      patient suffered trauma to his left shoulder resulting in fracture of his
      clavicle following an automobile accident and subsequently was found to have a
      pseudoaneurysm of his left suprascapular artery on imaging. This was treated by
      transarterial embolization, which resulted in immediate relief of his symptoms.
      Endoluminal management offers a safe and effective way of treating these lesions.

PMID- 20157501
TI  - Usefulness of 64-slice coronary computed tomographic angiography in the planning
      of percutaneous coronary intervention.

PMID- 20157503
TI  - The conscience of Vincent Van Gogh.

PMID- 20157502
TI  - Novel treatment approach to combat an infection with Acinetobacter.
AB  - The antimicrobial resistance of gram-negative pathogens has become problematic.
      In some cases related to Pseudomonas spp. and Acinetobacter spp., no
      antimicrobials on the market can be utilized at standard doses. We report a case
      of resistant Acinetobacter infection in a patient in the intensive care unit. In
      this scenario, we successfully treated the infection with doripenem at a higher
      dose of 1 g with a 4-hour infusion time along with the combination of tigecycline
      and colistin.

PMID- 20157504
TI  - Dr. Halsted at hopkins and at high hampton.

PMID- 20157505
TI  - Samuel Philip Marynick, MS, MD: a conversation with the editor.

PMID- 20157507
TI  - Endogenous DNA breaks: gammaH2AX and the role of telomeres.

PMID- 20157506
TI  - Is thymocyte development functional in the aged?
AB  - T cells are an integral part of a functional immune system with the majority
      being produced in the thymus. Of all the changes related to immunosenescence,
      regression of the thymus is considered one of the most universally recognised
      alterations. Despite the reduction of thymic size, there is evidence to suggest
      that T cell output is still present into old age, albeit much diminished; leading
      to the assumption that thymocyte development is normal. However, current data
      suggests that recent thymic emigrant from the aged thymus are functionally less
      responsive, giving rise to the possibility that the generation of naive T cell
      may be intrinsically impaired in the elderly. In light of these findings we
      discuss the evidence that suggest aged T cells may be flawed even before exiting
      to the periphery and could contribute to the age-associated decline in immune
      function.

PMID- 20157508
TI  - Chromatin modifications: the driving force of senescence and aging?
AB  - An emerging field of investigation in the search for treatment of human disease
      is the modulation of chromatin modifications. Chromatin modifications impart
      virtually all processes occurring in the mammalian nucleus, from regulation of
      transcription to genomic stability and nuclear high order organization. It has
      been well recognized that, as the mammalian cell ages, its chromatin structure
      evolves, both at a global level and at specific loci. While these observations
      are mostly correlative, recent technical developments allowing loss-of-function
      experiments and genome-wide approaches have permitted the identification of a
      causal relationship between specific changes in chromatin structure and the aging
      phenotype. Here we review the evidence pointing to the modulation of chromatin
      structure as a potential driving force of cellular aging in mammals.

PMID- 20157509
TI  - A screen of apoptosis and senescence regulatory genes for life span effects when
      over-expressed in Drosophila.
AB  - Conditional expression of transgenes in Drosophila was produced using the
      Geneswitch system, wherein feeding the drug RU486/Mifepristone activates the
      artificial transcription factor Geneswitch. Geneswitch was expressed using the
      Actin5C promoter and this was found to yield conditional, tissue-general
      expression of a target transgene (UAS-GFP) in both larvae and adult flies.
      Nervous system-specific (Elav-GS) and fat body-specific Geneswitch drivers were
      also characterized using UAS-GFP. Fourteen genes implicated in growth, apoptosis
      and senescence regulatory pathways were over-expressed in adult flies or during
      larval development, and assayed for effects on adult fly life span. Over
      expression of a dominant p53 allele (p53-259H) in adult flies using the
      ubiquitous driver produced increased life span in females but not males,
      consistent with previous studies. Both wingless and Ras activated form transgenes
      were lethal when expressed in larvae, and reduced life span when expressed in
      adults, consistent with results from other model systems indicating that the
      wingless and Ras pathways can promote senescence. Over-expression of the caspase
      inhibitor baculovirus p35 during larval development reduced the mean life span of
      male and female adults, and also produced a subset of females with increased life
      span. These experiments suggest that baculovirus p35 and the wingless and Ras
      pathways can have sex-specific and developmental stage-specific effects on adult
      Drosophila life span, and these reagents should be useful for the further
      analysis of the role of these conserved pathways in aging.

PMID- 20157510
TI  - Telomere-dependent and telomere-independent origins of endogenous DNA damage in
      tumor cells.
AB  - Human tumors and cultured cells contain elevated levels of endogenous DNA damage
      resulting from telomere dysfunction, replication and transcription errors,
      reactive oxygen species, and genome instability. However, the contribution of
      telomere-associated versus telomere-independent endogenous DNA lesions to this
      damage has never been examined. In this study, we characterized the relative
      amounts of these two types of DNA damage in five tumor cell lines by noting
      whether gamma-H2AX foci, generally considered to mark DNA double-strand breaks
      (DSBs), were on chromosome arms or at chromosome ends. We found that while the
      numbers of non-telomeric DSBs were remarkably similar in these cultures,
      considerable variation was detected in the level of telomeric damage. The
      distinct heterogeneity in the numbers of gamma-H2AX foci in these tumor cell
      lines was found to be due to foci associated with uncapped telomeres, and the
      amount of total telomeric damage also appeared to inversely correlate with the
      telomerase activity present in these cells. These results indicate that damaged
      telomeres are the major factor accounting for the variability in the amount of
      DNA DSB damage in tumor cells. This characterization of DNA damage in tumor cells
      helps clarify the contribution of non-telomeric DSBs and damaged telomeres to
      major genomic alterations.

PMID- 20157511
TI  - WRN helicase defective in the premature aging disorder Werner syndrome
      genetically interacts with topoisomerase 3 and restores the top3 slow growth
      phenotype of sgs1 top3.
AB  - Werner syndrome (WS) is a premature aging disorder characterized by genomic
      instability. The WRN gene defective in WS encodes a protein with both helicase
      and exonuclease activities that interacts with proteins implicated in DNA
      metabolism. To understand its genetic functions, we examined the ability of human
      WRN to rescue phenotypes associated with sgs1, the sole RecQ helicase in
      Saccharomyces cerevisiae. WRN failed to rescue sgs1 sensitivity to the DNA
      damaging agent methylmethane sulfonate or replication inhibitor hydroxyurea,
      suggesting divergent functions of human and yeast RecQ helicases. However,
      physiological expression of WRN in sgs1 top3 restored top3 slow growth phenotype,
      whereas no effect on growth was observed with wild-type or sgs1 strains. Slow
      growth of WRN-transformed sgs1 top3 correlated with an elevated population of
      large-budded cells with undivided nuclei, indicating restoration of cell cycle
      delay in late S/G2 characteristic of top3. WRN helicase but not exonuclease
      activity was genetically required for restoration of top3 growth phenotype,
      demonstrating separation of function of WRN catalytic activities. A naturally
      occurring missense polymorphism in WRN that interferes with helicase activity
      abolished its ability to restore top3 slow growth phenotype. Proposed roles of
      WRN in genetic pathways important for the suppression of genomic instability are
      discussed.

PMID- 20157512
TI  - Cyclooxygenase-1 null mice show reduced neuroinflammation in response to beta
      amyloid.
AB  - Several independent epidemiological studies indicate that chronic use of non
      steroidal anti-inflammatory drugs can reduce the risk of developing Alzheimer's
      disease (AD), supporting the inflammatory cascade hypothesis. Although the first
      clinical trial with indomethacin, a preferential cyclooxygenase (COX)-1
      inhibitor, showed beneficial effects, subsequent large clinical trials, mostly
      using COX-2 inhibitors, failed to show any beneficial effect in AD patients with
      mild to severe cognitive impairment. These combined data suggest that either an
      early treatment is crucial to stop the mechanisms underlying the disease before
      the onset of the symptoms, or that preferential COX-1 inhibition, rather than COX
      2, is beneficial. Therefore, a full understanding of the physiological,
      pathological, and/or neuroprotective role of COX isoforms may help to develop
      better therapeutic strategies for the prevention or treatment of AD. In this
      study, we examined the effect of COX-1 genetic deletion on the inflammatory
      response and neurodegeneration induced by beta-amyloid. beta-amyloid (Abeta(1
      42)) was centrally injected in the lateral ventricle of COX-1-deficient (COX-1(-/
      )) and their respective wild-type (WT) mice. In COX-1(-/-) mice, Abeta(1-42)
      induced inflammatory response and neuronal damage were attenuated compared to WT
      mice, as shown by Fluoro-Jade B and nitrotyrosine staining. These results
      indicate that inhibition of COX-1 activity may be valid therapeutic strategy to
      reduce brain inflammatory response and neurodegeneration.

PMID- 20157513
TI  - Identification of Peroxiredoxin 1 as a novel interaction partner for the lifespan
      regulator protein p66Shc.
AB  - Damage caused by reactive oxygen species (ROS) contributes to many aging
      processes and accompanying diseases. ROS are toxic side products of cellular
      respiration, but also function as signal, e.g. in the mitochondrial apoptosis
      pathway. The protein p66Shc, which has been implicated in life-span regulation
      and aging-related diseases, is a central player in stress-induced apoptosis and
      the associated ROS burst. Stress signals, such as UV radiation or ROS themselves,
      activate p66Shc, which was proposed to stimulate its H(2)O(2) forming activity,
      ultimately triggering mitochondrial disintegration. However, mechanistic details
      of H(2)O(2) formation and apoptosis induction by p66Shc and regulation of these
      activities remain to be revealed. Here, we describe the effects of Ser36
      phosphorylation and Pin1 binding on p66Shc activity, and the identification of
      Peroxiredoxin 1 (Prx1) as a novel interaction partner for the unique p66Shc N
      terminal domain. Prx1 was identified in affinity experiments as dominant
      interaction partner. Complex formation leads to disassembly of Prx1 decamers,
      which is known to increase its peroxidase activity. The interaction leads to
      reduction of the p66CH2CB tetramer, which reduces its ability to induce
      mitochondrial rupture. Our results indicate that p66CH2CB and Prx1 form a stress
      sensing complex that keeps p66Shc inactive at moderate stress levels.

PMID- 20157514
TI  - Positive association of common variants in CD36 with neovascular age-related
      macular degeneration.
AB  - Age-related macular degeneration (AMD) is a leading cause of legal blindness
      among older individuals of industrialized countries. In neovascular AMD, which is
      an advanced stage of AMD, choroidal neovascularization develops underneath the
      macula and destroys central vision. Oxidative stress is a hypothesized pathway
      for the pathophysiology of AMD. CD36 was chosen as a candidate gene for
      neovascular AMD because the protein plays an important role in this pathway as
      well as in angiogenesis and in maintaining chorioretinal homeostasis. We tested
      19 tag single nucleotide polymorphisms (SNPs) across CD36 for their association
      with the disease in a Japanese population comprising 109 neovascular AMD subjects
      and 182 unrelated controls. Five of the 19 SNPs demonstrated a nominally
      significant association with neovascular AMD (P < 0.05), of which two (rs3173798
      and rs3211883) withstood Bonferroni correction for multiple testing (rs3173798,
      nominal P = 9.96 x 10-4, allele-specific odds ratio = 0.55; rs3211883, nominal P
      = 2.09 x 10-4, allele-specific odds ratio = 0.50). Population structure analyses
      excluded stratification artifacts in our study cohort. This study supports the
      candidacy of CD36 as a novel susceptibility gene for neovascular AMD. Replication
      of our results in other populations will provide further convincing evidence for
      the genetic association.

PMID- 20157515
TI  - Partners in death: a role for p73 and NF-kB in promoting apoptosis.

PMID- 20157516
TI  - Anti-aging protein SIRT1: a role in cervical cancer?

PMID- 20157517
TI  - Validation of anti-aging drugs by treating age-related diseases.
AB  - Humans die from age-related diseases, which are deadly manifestations of the
      aging process. In order to extend life span, an anti-aging drug must delay age
      related diseases. All together age-related diseases are the best biomarker of
      aging. Once a drug is used for treatment of any one chronic disease, its effect
      against other diseases (atherosclerosis, cancer, prostate enlargement,
      osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age
      related macular degeneration) may be evaluated in the same group of patients. If
      the group is large, then the anti-aging effect could be validated in a couple of
      years. Startlingly, retrospective analysis of clinical and preclinical data
      reveals four potential anti-aging modalities.

PMID- 20157518
TI  - Sequence-specific processing of telomeric 3' overhangs by the Werner syndrome
      protein exonuclease activity.
AB  - Werner syndrome is a premature aging disease caused by loss of function mutations
      in the Werner syndrome protein (WRN) gene. WRN is a RecQ helicase that in
      contrast to every other member of this family of proteins possesses an
      exonuclease activity. The findings that cells lacking WRN activity display
      accelerated telomere shortening and WRN can be detected at chromosome ends
      suggest that this protein participates in some aspects of telomere metabolism. In
      this study we examined the impact of WRN on telomeric substrates with a 3' single
      stranded overhang in vitro and show that WRN has sequence-specific exonuclease
      activity that removes several nucleotides inward with a periodical pattern from
      the 3' end of the telomeric overhang. This activity is strictly dependent on the
      presence of telomeric sequences in both the duplex DNA and 3' overhang DNA
      segment and is strongly inhibited by the telomeric factor POT1 but not TRF2.
      These data demonstrate that WRN processes telomeric DNA substrates with a 3'
      single-stranded overhang with high specificity and suggest that this protein
      could influence the configuration of telomere ends prior to the formation of a
      protective t-loop structure.

PMID- 20157519
TI  - Oncogenic viral protein HPV E7 up-regulates the SIRT1 longevity protein in human
      cervical cancer cells.
AB  - Senescence is blocked in human cervical keratinocytes infected with high risk
      human papillomavirus (e.g. HPV type16). Viral oncoproteins HPV E6 and HPV E7
      access the cell cycle via cellular p53 and retinoblastoma proteins respectively.
      Previously we have shown that HPV E7, not HPV E6, is also responsible for
      cervical cancer cell survival (SiHa cells; HPV type16). We now present evidence
      that SIRT1, an aging-related NAD-dependent deacetylase, mediates HPV E7 survival
      function in SiHa cervical cancer cells. Moreover, HPV E7 up-regulates SIRT1
      protein when expressed in primary human keratinocytes. Conversely, SIRT1 levels
      decrease following RNAi-mediated silencing of HPV E7 in SiHa cells. Silencing HPV
      E6 has no effect on SIRT1 but, as expected, causes marked accumulation of p53
      protein accompanied by p53-mediated up-regulation of p21. However, p53
      acetylation (K382Ac) was barely detectable. Since p53 is a known SIRT1 substrate
      we propose that elevated SIRT1 levels (induced by HPV E7) attenuate p53 pro
      apoptotic capacity via its de-acetylation. Our discovery that HPV E7 up-regulates
      SIRT1 links a clinically important oncogenic virus with the multi-functional
      SIRT1 protein. This link may open the way for a more in-depth understanding of
      the process of HPV-induced malignant transformation and also of the inter
      relationships between aging and cancer.

PMID- 20157520
TI  - The S-adenosylmethionine dependent O-methyltransferase PaMTH1: a longevity
      assurance factor protecting Podospora anserina against oxidative stress.
AB  - PaMTH1 is an O-methyltransferase catalysing the methylation of vicinal hydroxyl
      groups of polyphenols. The protein accumulates during ageing of Podospora
      anserina in both the cytosol and in the mitochondrial matrix. The construction
      and characterisation of a PaMth1 deletion strain provided additional evidence
      about the function of the protein in the protection against metal induced
      oxidative stress. Deletion of PaMth1 was found to lead to a decreased resistance
      against exogenous oxidative stress and to a shortened lifespan suggesting a role
      of PaMTH1 as a longevity assurance factor in a new molecular pathway involved in
      lifespan control.

PMID- 20157521
TI  - A role for cyclooxygenase-1 in beta-amyloid-induced neuroinflammation.

PMID- 20157522
TI  - A "radical" mitochondrial view of autophagy-related pathology.

PMID- 20157523
TI  - Growth and aging: a common molecular mechanism.
AB  - It is commonly assumed that growth and aging are somehow linked, but the nature
      of this link has been elusive. Here we review the aging process as a continuation
      of TOR-driven growth. TOR is absolutely essential for developmental growth, but
      upon completion of development it causes aging and age-related diseases. Thus,
      the nutrient-sensing and growth-promoting TOR signaling pathway may provide a
      molecular link between growth and aging that is universal from yeast to human.

PMID- 20157524
TI  - The neuronal cell cycle as a mechanism of pathogenesis in Alzheimer's disease.
AB  - Differentiated neurons display specific biochemical, physiological and
      morphological properties that apparently prevent them from further cell division.
      Nevertheless, expression of cell cycle modulators persists after neuronal
      differentiation and is upregulated under stress conditions, such as trophic
      factor deprivation, oxidative stress and the presence of DNA damaging agents.
      This apparent reactivation of the cell cycle has been postulated as a sine qua
      non for neuronal death in response to those stress conditions, particularly in
      Alzheimer's disease. However, the physiological and pathogenic implications of a
      putative neuronal cell cycle are far from clear. Here, we discuss the notion of
      the neuronal cell cycle as a mediator of cell death, with particular emphasis on
      Alzheimer's disease.

PMID- 20157527
TI  - Keeping your senescent cells under control.

PMID- 20157526
TI  - Mitochondrial dysfunction and oxidative stress mediate the physiological
      impairment induced by the disruption of autophagy.
AB  - Impaired or deficient autophagy is believed to cause or contribute to aging, as
      well as a number of age-related pathologies. The exact mechanism through which
      alterations in autophagy induce these various pathologies is not well understood.
      Here we describe the creation of two in vivo mouse models that allow for the
      characterization of the alteration in mitochondrial function and the contribution
      of the corresponding oxidative stress following deletion of Atg7. Using these
      models we demonstrate that isolated mitochondria obtained from Atg7(-/-) skeletal
      muscle exhibit a significant defect in mitochondrial respiration. We further show
      that cells derived from Atg7(-/-) mice have an altered metabolic profile
      characterized by decreased resting mitochondrial oxygen consumption and a
      compensatory increase in basal glycolytic rates. Atg7(-/-)cells also exhibit
      evidence for increased steady state levels of reactive oxygen species. The
      observed mitochondrial dysfunction and oxidative stress is also evident in a
      mouse model where Atg7 is deleted within the pancreatic beta cell. In this model,
      the simple administration of an antioxidant can significantly ameliorate the
      physiological impairment in glucose-stimulated insulin secretion. Taken together,
      these results demonstrate the potential role of mitochondrial dysfunction and
      oxidative stress in autophagy related pathology.

PMID- 20157525
TI  - Aging of the inceptive cellular population: the relationship between stem cells
      and aging.
AB  - The average life expectancy worldwide has about doubled and the global population
      has increased six fold over the past century. With improving health care in the
      developed world there is a proportional augmentation in the treatment necessary
      for elderly patients occasioning the call for increased research in the area of
      aging and age-related diseases. The manifestation of this research has been
      focalized on the causative cellular processes and molecular mechanisms involved.
      Here we will discuss the efforts of this research in the area of stem cells,
      delving into the regulatory mechanisms and how their de-regulation could be
      attributed to aging and age-related diseases.

PMID- 20157528
TI  - SNP'ing for longevity.

PMID- 20157529
TI  - Adaptation, aging, and genomic information.
AB  - Aging is not simply an accumulation of damage or inappropriate higher-order
      signaling, though it does secondarily involve both of these subsidiary
      mechanisms. Rather, aging occurs because of the extensive absence of adaptive
      genomic information required for survival to, and function at, later adult ages,
      due to the declining forces of natural selection during adult life. This absence
      of information then secondarily leads to misallocations and damage at every level
      of biological organization. But the primary problem is a failure of adaptation at
      later ages. Contemporary proposals concerning means by which human aging can be
      ended or cured which are based on simple signaling or damage theories will thus
      reliably fail. Strategies based on reverse-engineering age-extended adaptation
      using experimental evolution and genomics offer the prospect of systematically
      greater success.

PMID- 20157530
TI  - Counteracting muscle wasting in aging and neuromuscular diseases: the critical
      role of IGF-1.
AB  - Most muscle pathologies are characterized by the progressive loss of muscle
      tissue due to chronic degeneration combined with the inability of regeneration
      machinery to replace the damaged muscle. These pathological changes, known as
      muscle wasting, can be attributed to the activation of several proteolytic
      systems, such as calpain, ubiquitin-proteasome and caspases, and to the
      alteration in muscle growth factors. Among them, insulin-like growth factor-1
      (IGF-1) has been implicated in the control of skeletal muscle growth,
      differentiation, survival, and regeneration and has been considered a promising
      therapeutic agent in staving off the advance of muscle weakness. Here we review
      the molecular basis of muscle wasting associated with diseases, such as
      sarcopenia, muscular dystrophy and Amyotrophic Lateral Sclerosis, and discuss the
      potential therapeutic role of local IGF-1 isoforms in muscle aging and diseases.

PMID- 20157531
TI  - Poly(ADP-ribose) polymerase 1 at the crossroad of metabolic stress and
      inflammation in aging.
AB  - Poly(ADP-ribose) polymerase 1 (PARP1) is a chromatin-associated nuclear protein,
      which functions as molecular stress sensor. Reactive oxygen species, responsible
      for the most plausible and currently acceptable global mechanism to explain the
      aging process, strongly activate the enzymatic activity of PARP1 and the
      formation of poly(ADP-ribose) (PAR) from NAD(+). Consumption of NAD(+) links
      PARP1 to energy metabolism and to a large number of NAD(+)-dependent enzymes,
      such as the sirtuins. As transcriptional cofactor for NF-kappaB-dependent gene
      expression, PARP1 is also connected to the immune response, which is implicated
      in almost all age-related or associated diseases. Accordingly, numerous
      experimental studies have demonstrated the beneficial effects of PARP inhibition
      for several age-related diseases. This review summarizes recent findings on PARP1
      and puts them in the context of metabolic stress and inflammation in aging.

PMID- 20157532
TI  - The regulation of p53 by phosphorylation: a model for how distinct signals
      integrate into the p53 pathway.
AB  - The tumour suppressor p53 is a transcription factor that has evolved the ability
      to integrate distinct environmental signals including DNA damage, virus
      infection, and cytokine signaling into a common biological outcome that maintains
      normal cellular control. Mutations in p53 switch the cellular transcription
      program resulting in deregulation of the stress responses that normally maintain
      cell and tissue integrity. Transgenic studies in mice have indicated that changes
      in the specific activity of p53 can have profound effects not only on cancer
      development, but also on organism aging. As the specific activity of p53 is
      regulated at a post-translational level by sets of enzymes that mediate
      phosphorylation, acetylation, methylation, and ubiquitin-like modifications, it
      is likely that physiological modifiers of the aging function of p53 would be
      enzymes that catalyze such covalent modifications. We demonstrate that distinct
      stress-activated kinases, including ataxia telangiectasia mutated (ATM), casein
      kinase 1 (CK1) and AMP-activated protein kinase (AMPK), mediate phosphorylation
      of a key phospho-acceptor site in the p53 transactivation domain in response to
      diverse stresses including ionizing radiation, DNA virus infection, and elevation
      in the intracellular AMP/ATP ratio. As diseases linked to aging can involve
      activation of p53-dependent changes in cellular protective pathways, the
      development of specific physiological models might further shed light on the role
      of p53 kinases in modifying age-related diseases.

PMID- 20157533
TI  - P66Shc signals to age.
AB  - Oxygen metabolism is thought to impact on aging through the formation of reactive
      oxygen species (ROS) that are supposed to damage biological molecules. The study
      of p66(Shc), a crucial regulator of ROS level involved in aging dysfunction,
      suggests that the incidence of degenerative disease and longevity are determined
      by a specific signaling function of ROS other than their unspecific damaging
      property.

PMID- 20157534
TI  - Inhibition of S6K by resveratrol: in search of the purpose.

PMID- 20157535
TI  - Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy.
AB  - Resveratrol is a plant-derived polyphenol that promotes health and disease
      resistance in rodent models, and extends lifespan in lower organisms. A major
      challenge is to understand the biological processes and molecular pathways by
      which resveratrol induces these beneficial effects. Autophagy is a critical
      process by which cells turn over damaged components and maintain bioenergetic
      requirements. Disruption of the normal balance between pro- and anti-autophagic
      signals is linked to cancer, liver disease, and neurodegenerative disorders. Here
      we show that resveratrol attenuates autophagy in response to nutrient limitation
      or rapamycin in multiple cell lines through a pathway independent of a known
      target, SIRT1. In a large-scalein vitro kinase screen we identified p70 S6 kinase
      (S6K1) as a target of resveratrol. Blocking S6K1 activity by expression of a
      dominant-negative mutant or RNA interference is sufficient to disrupt autophagy
      to a similar extent as resveratrol. Furthermore, co-administration of resveratrol
      with S6K1 knockdown does not produce an additive effect. These data indicate that
      S6K1 is important for the full induction of autophagy in mammals and raise the
      possibility that some of the beneficial effects of resveratrol are due to
      modulation of S6K1 activity.

PMID- 20157536
TI  - dSir2 mediates the increased spontaneous physical activity in flies on calorie
      restriction.
AB  - Calorie restriction (CR) is the most effective way to increase life span and
      delay the onset of age-related symptoms in animals. We have previously reported
      that CR affects a variety of physiological phenotypes in flies and results in
      dramatic behavioral, physical and demographic changes. Here we show effects of
      low and high calorie levels on the spontaneous physical activity of flies. Wild
      type flies maintained on a low calorie diet exhibit higher spontaneous activity
      compared to flies on higher calorie diets. This increase is dependent on the
      presence of Sir2 since a low calorie diet does not increase the activity of dSir2
      null flies. Similarly, increasing dSir2 activity by feeding flies resveratrol, a
      CR mimetic, increases spontaneous physical activity of flies on high caloric
      food. In Drosophila, spontaneous physical activity therefore closely mimics life
      span in its dependence on Sir2.

PMID- 20157537
TI  - The relative contributions of the p53 and pRb pathways in oncogene-induced
      melanocyte senescence.
AB  - Oncogene-induced senescence acts as a barrier against tumour formation and has
      been implicated as the mechanism preventing the transformation of benign
      melanocytic lesions that frequently harbour oncogenic B-RAF or N-RAS mutations.
      In the present study we systematically assessed the relative importance of the
      tumour suppressor proteins p53, p21(Waf1), pRb and p16(INK4a) in mediating
      oncogene-induced senescence in human melanocytes. We now show that oncogenic N
      RAS induced senescence in melanocytes is associated with DNA damage, a potent DNA
      damage response and the activation of both the p16(INK4a)/pRb and p53/p21(Waf1)
      tumour suppressor pathways. Surprisingly neither the pharmacological inhibition
      of the DNA damage response pathway nor silencing of p53 expression had any
      detectable impact on oncogene-induced senescence in human melanocytes. Our data
      indicate that the pRb pathway is the dominant effector of senescence in these
      cells, as its specific inactivation delays the onset of senescence and weakens
      oncogene-induced proliferative arrest. Furthermore, we show that although both
      p16(INK4a) and p21(Waf1) are upregulated in response to N-RAS(Q61K), the
      activities of these CDK inhibitors are clearly distinct and only the loss of
      p16(INK4a) weakens senescence. We propose that the ability of p16(INK4a) to
      inhibit the cyclin D-dependent kinases and DNA replication, functions not shared
      by p21(Waf1), contribute to its role in senescence. Thus, in melanocytes with
      oncogenic signalling only p16(INK4a) can fully engage the pRb pathway to alter
      chromatin structure and silence the genes that are required for proliferation.

PMID- 20157539
TI  - Urea cycle regulation by mitochondrial sirtuin, SIRT5.
AB  - Mammalian sirtuins have diverse roles in aging, metabolism and disease. Recently
      we reported a new function for SIRT5 in urea cycle regulation. Our study
      uncovered that SIRT5 localized to mitochondria matrix and deacetylates carbamoyl
      phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting
      step of urea cycle. Deacetylation of CPS1 by SIRT5 resulted in activation of CPS1
      enzymatic activity. Indeed, SIRT5-deficient mice failed to up-regulate CPS1
      activity and showed hyper ammonemia during fasting. Similar effects are also
      observed on high protein diet or calorie restriction. These data indicate SIRT5
      also has an emerging role in the metabolic adaptation to fasting, high protein
      diet and calorie restriction.

PMID- 20157538
TI  - Heat shock proteins in long-lived worms and mice with insulin/insulin-like
      signaling mutations.
AB  - Heat shock proteins (HSPs) have proven to be effective tools for extending
      invertebrate lifespan, and in C. elegans daf-2 mutants, longevity resulting from
      loss of insulin/insulin-like signals is at least partly dependent upon elevated
      HSP expression. In mice, inhibition of the orthologous growth hormone/insulin
      like growth factor I (GH/IGF-I) pathway has similar pro-longevity effects. A
      recent study, however, suggests that loss of GH/IGF-I signals in long-lived mice
      does not broadly elevate HSP expression, but in fact decreases HSP expression in
      many tissue types, such as liver and kidney. The contribution of chaperones to
      the longevity of long-lived mice with altered GH/IGF-I signals may therefore
      differ from that described in C. elegans daf-2 mutants. This result, in
      combination with other recent findings, underscores the possibility that systemic
      overexpression of chaperones will have dissimilar effects on longevity in
      vertebrate and invertebrate systems.

PMID- 20157540
TI  - GSK3beta and aging liver.
AB  - The loss of regenerative capacity of tissues is one of the major characteristics
      of aging. Liver represents a powerful system for investigations of mechanisms by
      which aging reduces regenerative capacity of tissues. The studies within last
      five years revealed critical role of epigenetic silencing in the inhibition of
      liver proliferation in old mice. These studies have shown that a number of cell
      cycle proteins are silenced in livers of old mice by C/EBPalpha-HDAC1-Brm complex
      and that old liver fails to reduce the complex and activate these genes in
      response to proliferative stimulus such as partial hepatectomy. The complex
      modifies histone H3 on the promoters of c-myc and FoxM1B in the manner which
      prevents expression of these genes. Despite this progress, little is known about
      mechanisms by which aging causes this epigenetic silencing. We have recently
      discovered signal transduction pathways which operate upstream of the C/EBPalpha
      HDAC1-Brm complex. These pathways involve communications of growth hormone,
      GSK3beta and cyclin D3. In addition to the liver, GH-GSK3beta-cyclin D3 pathway
      is also changed with age in lung, brain and adipose tissues. We suggest that
      other age-associated alterations in these tissues might be mediated by the
      reduced levels of GSK3beta and by elevation of cyclin D3. In this review, we
      summarize these new data and discuss the role of such alterations in the
      development of aging phenotype in the liver and in other tissues.

PMID- 20157541
TI  - mTOR's role in ageing: protein synthesis or autophagy?
AB  - The molecular and cellular mechanisms that regulate ageing are currently under
      scrutiny because ageing is linked to many human diseases. The nutrient sensing
      TOR pathway is emerging as a key regulator of ageing. TOR signaling is complex
      affecting several crucial cellular functions and two such functions, which show
      clear effects on ageing, are protein synthesis and autophagy. In this article we
      discuss the relative importance of both these processes in ageing, identify how
      TOR regulates translation and autophagy and speculate on links between the TOR
      signaling network and ageing pathways.

PMID- 20157542
TI  - A structural basis for cellular senescence.
AB  - Replicative senescence (RS) that limits the proliferating potential of normal
      eukaryotic cells occurs either by a cell-division counting mechanism linked to
      telomere erosion or prematurely through induction by cell stressors such as
      oncogene hyper-activation. However, there is evidence that RS also occurs by a
      stochastic process that is independent of number of cell divisions or cellular
      stress and yet it leads to a highly-stable, non-reversible post-mitotic state
      that may be long-lasting and that such a process is widely represented among
      higher eukaryotes. Here I present and discuss evidence that the interactions
      between DNA and the nuclear substructure, commonly known as the nuclear matrix,
      define a higher-order structure within the cell nucleus that following
      thermodynamic constraints, stochastically evolves towards maximum stability, thus
      becoming limiting for mitosis to occur. It is suggested that this process is
      responsible for ultimate replicative senescence and yet it is compatible with
      long-term cell survival.

PMID- 20157543
TI  - Telomere length regulates ISG15 expression in human cells.
AB  - Endogenous genes regulated by telomere length have not previously been identified
      in human cells. Here we show that telomere length regulates the expression of
      interferon stimulated gene 15 (ISG15, 1p36.33). ISG15 expression (RNA and
      protein) increases in human cells with short telomeres, and decreases following
      the elongation of telomeres by human telomerase reverse transcriptase (hTERT).
      The short-telomere-dependent up-regulation of ISG15 is not mediated by
      replicative senescence/DNA damage signaling or type I interferons. In human skin
      specimens obtained from various aged individuals, ISG15 is up-regulated in a
      subset of cells in older individuals. Our results demonstrate that endogenous
      human genes can be regulated by the length of telomeres prior to the onset of DNA
      damage signals, and suggest the possibility that cell turnover/telomere
      shortening may provide a mechanism for adjusting cellular physiology. The
      upregulation of ISG15 with telomere shortening may contribute to chronic
      inflammatory states associated with human aging.

PMID- 20157544
TI  - The mitochondrial ribosomal protein of the large subunit, Afo1p, determines
      cellular longevity through mitochondrial back-signaling via TOR1.
AB  - Yeast mother cell-specific aging constitutes a model of replicative aging as it
      occurs in stem cell populations of higher eukaryotes. Here, we present a new long
      lived yeast deletion mutation,afo1 (for aging factor one), that confers a 60%
      increase in replicative lifespan. AFO1/MRPL25 codes for a protein that is
      contained in the large subunit of the mitochondrial ribosome. Double mutant
      experiments indicate that the longevity-increasing action of the afo1 mutation is
      independent of mitochondrial translation, yet involves the cytoplasmic Tor1p as
      well as the growth-controlling transcription factor Sfp1p. In their final cell
      cycle, the long-lived mutant cells do show the phenotypes of yeast apoptosis
      indicating that the longevity of the mutant is not caused by an inability to
      undergo programmed cell death. Furthermore, the afo1 mutation displays high
      resistance against oxidants. Despite the respiratory deficiency the mutant has
      paradoxical increase in growth rate compared to generic petite mutants. A
      comparison of the single and double mutant strains for afo1 and fob1 shows that
      the longevity phenotype of afo1 is independent of the formation of ERCs
      (ribosomal DNA minicircles). AFO1/MRPL25 function establishes a new connection
      between mitochondria, metabolism and aging.

PMID- 20157545
TI  - The role of p38b MAPK in age-related modulation of intestinal stem cell
      proliferation and differentiation in Drosophila.
AB  - It is important to understand how age-related changes in intestinal stem cells
      (ISCs) may contribute to age-associated intestinal diseases, including cancer.
      Drosophila midgut is an excellent model system for the study of ISC proliferation
      and differentiation. Recently, age-related changes in the Drosophila midgut have
      been shown to include an increase in ISC proliferation and accumulation of mis
      differentiated ISC daughter cells. Here, we show that the p38b MAPK pathway
      contributes to the age-related changes in ISC and progenitor cells in Drosophila.
      D-p38b MAPK is required for an age-related increase of ISC proliferation. In
      addition, this pathway is involved in age and oxidative stress-associated mis
      differentiation of enterocytes and upregulation of Delta, a Notch receptor
      ligand. Furthermore, we also show that D-p38b acts downstream of PVF2/PVR
      signaling in these age-related changes. Taken together, our findings suggest that
      p38 MAPK plays a crucial role in the balance between ISC proliferation and proper
      differentiation in the adult Drosophila midgut.

PMID- 20157546
TI  - Serum markers of apoptosis decrease with age and cancer stage.
AB  - The physical manifestations of aging reflect a loss of homeostasis that effects
      molecular, cellular and organ system functional capacity. As a sentinel
      homeostatic pathway, changes in apoptosis can have pathophysiological
      consequences in both aging and disease. To assess baseline global apoptosis
      balance, sera from 204 clinically normal subjects had levels of sFas (inhibitor
      of apoptosis), sFasL (stimulator of apoptosis), and total cytochrome c (released
      from cells during apoptosis) measured. Serum levels of sFas were significantly
      higher while sFasL and cytochrome c levels were lower in men compared to women.
      With increasing age there was a decrease in apoptotic markers (cytochrome c) and
      pro-apoptotic factors (sFasL) and an increase in anti-apoptotic factors (sFas) in
      circulation. The observed gender differences are consistent with the known
      differences between genders in mortality and morbidity. In a separate cohort,
      subjects with either breast (n = 66) or prostate cancer (n = 38) exhibited
      significantly elevated sFas with reduced sFasL and total cytochrome c regardless
      of age. These markers correlated with disease severity consistent with tumor
      subversion of apoptosis. The shift toward less global apoptosis with increasing
      age in normal subjects is consistent with increased incidence of diseases whose
      pathophysiology involves apoptosis dysregulation.

PMID- 20157547
TI  - "Shping 2" different cellular localizations - a potential new player in aging
      processes.
AB  - The functions of the ubiquitously expressed protein tyrosine phosphatase Shp-2
      are dependent on its localization. Cytosolic Shp-2 is known to modulate different
      pathways involved in cell growth, cell development, tissue inflammation and
      cellular chemotaxis. But Shp-2 is also localized in the nucleus and the
      mitochondria. Nuclear Shp-2 forms a complex with the signal transducer and
      activator of transcription 5 (STAT5) which then binds to DNA and regulates
      transcription of milk genes. In contrast, nuclear Shp-2 dephosphorylates STAT1
      and thereby inhibits gene transcription. In addition, it counteracts the
      oxidative stress dependent nuclear export of Telomerase Reverse Transcriptase
      (TERT) mediated by members of the Src kinase family, a process leading to
      replicative senescence. For the recently found mitochondrial Shp-2 an involvement
      in the regulation of the cellular redox balance is discussed. Shp-2 shows the
      ability to regulate reactive oxygen species formation in the mitochondria. There
      are hints that mitochondrial Shp-2 and Src are involved in the regulation of
      respiratory chain activity. Since a substantial fraction of TERT has been found
      in the mitochondria, it is hypothesized that mitochondrial Shp-2 acts as a
      positive regulator of TERT in the mitochondria, similar to its nuclear role.
      Taken together, Shp-2 seems to be a new player in aging processes.

PMID- 20157548
TI  - SIRT1 performs a balancing act on the tight-rope toward longevity.
AB  - Our recent study defined a new role for SIRT1 as a regulator of hepatic lipid
      metabolism. In the liver a major target of this sirtuin is the PPARalpha/PGC
      1alpha signaling axis. Ablation of SIRT1 in the liver results in disrupted fatty
      acid oxidation, increased cellular stress, and elevations in proinflammatory
      cytokines. However, contrary to previous studies, we observed no changes in
      glucose production in the absence of SIRT1, despite impaired PGC-1alpha
      signaling. These findings point toward the involvement of other players in SIRT1
      regulated hepatic metabolism. Here we discuss our findings, and comment on some
      of the controversy surrounding this protein in the current literature.

PMID- 20157549
TI  - CXCL5 drives obesity to diabetes, and further.
AB  - We have recently shown that the CXCL5 chemokine is secreted by adipose tissue in
      the obese state. We demonstrated that adipose tissue-derived CXCL5 mediates
      insulin resistance in muscle. We speculate in this paper that CXCL5 could also
      mediate other obesity, and diabetes-derived pathologies, such as cardiovascular
      disease, retinopathy, or inflammatory bowel disease. In this scenario CXCL5
      targeted therapy would prevent not only the development of type II diabetes in
      obese subjects, but also several other obesity-related co morbidities. Finally we
      propose to analyze the CXCL5 gene to find particular polymorphisms that could
      predict the development of type II diabetes in obese subjects.

PMID- 20157550
TI  - Role of NFkappaB in age-related vascular endothelial dysfunction in humans.

PMID- 20157551
TI  - Tissue- and age-dependent expression of RNA-binding proteins that influence mRNA
      turnover and translation.
AB  - Gene expression patterns vary dramatically in a tissue-specific and age-dependent
      manner. RNA-binding proteins that regulate mRNA turnover and/or translation (TTR
      RBPs) critically affect the subsets of expressed proteins. However, very little
      is known regarding the tissue- and age-dependent expression of TTR-RBPs in
      humans. Here, we use human tissue arrays containing a panel of organ biopsies
      from donors of different ages, to study the distribution and abundance of four
      TTR-RBPs: HuR, AUF1, TIA-1, and TTP. HuR and AUF1 were expressed with remarkably
      similar patterns. Both TTR-RBPs were present in high percentages of cells and
      displayed elevated intensities in many age groups and tissues, most notably in
      the gastrointestinal and reproductive systems; they were moderately expressed in
      the urinary and immune systems, and were almost undetectable in muscle and brain.
      TIA-1 was also abundant in many tissues and age groups; TIA-1 was expressed at
      high levels in the gastrointestinal, immune, urinary, and reproductive systems,
      and at low levels in brain and muscle. By contrast, TTP-expressing cells, as well
      as TTP signal intensities declined with advancing age, particularly in the
      immune, nervous, and muscular systems; however, TTP levels remained elevated in
      the gastrointestinal tract. The widespread abundance of HuR, AUF1, and TIA-1
      throughout the body and in all age groups was in stark contrast with their
      declining levels in human diploid fibroblasts (HDFs) undergoing replicative
      senescence, a cultured-cell model of aging. Conversely, TTP levels increased in
      senescent HDFs, while TTP levels decreased with advancing age. Our studies
      provide a framework for the study of human TTR-RBP function in different tissues,
      throughout the human life span.

PMID- 20157552
TI  - Human insulin/IGF-1 and familial longevity at middle age.
AB  - Recently, we have shown that compared to controls, long-lived familial
      nonagenarians (mean age: 93.4 years) from the Leiden Longevity Study displayed a
      lower mortality rate, and their middle-aged offspring displayed a lower
      prevalence of cardio-metabolic diseases, including diabetes mellitus. The
      evolutionarily conserved insulin/IGF-1 signaling (IIS) pathway has been
      implicated in longevity in model organisms, but its relevance for human longevity
      has generated much controversy. Here, we show that compared to their partners,
      the offspring of familial nonagenarians displayed similar non-fasted serum levels
      of IGF-1, IGFBP3 and insulin but lower non-fasted serum levels of glucose,
      indicating that familial longevity is associated with differences in insulin
      sensitivity.

PMID- 20157553
TI  - What determines the switch between atrophic and neovascular forms of age related
      macular degeneration? - the role of BMP4 induced senescence.
AB  - Age-related macular degeneration (AMD), the leading cause of blindness in the
      elderly, targets the retinal pigment epithelium (RPE), a monolayer of cells at
      the back of the eye. As AMD progresses, it can develop into two distinct forms of
      late AMD: "dry," atrophic AMD, characterized by RPE senescence and geographic RPE
      loss, and "wet," neovascular AMD, characterized by RPE activation with abnormal
      growth of choroidal vessels. The genetic and molecular pathways that lead to
      these diverse phenotypes are currently under investigation. We have found that
      bone morphogenetic protein-4 (BMP4) is differentially expressed in atrophic and
      neovascular AMD. In atrophic AMD, BMP4 is highly expressed in RPE, and mediates
      oxidative stress induced RPE senescencein vitro via Smad and p38 pathways. In
      contrast, in neovascular AMD lesions, BMP4 expression in RPE is low, possibly a
      result of local expression of pro-inflammatory mediators. Thus, BMP4 may be
      involved in the molecular switch determining which phenotypic pathway is taken in
      the progression of AMD.

PMID- 20157554
TI  - Building a new bridge between metabolism, free radicals and longevity.

PMID- 20157555
TI  - Tristetraprolin: a weapon against HPV-induced cervical cancer?

PMID- 20157556
TI  - Awakening p53 in senescent cells using nutlin-3.

PMID- 20157557
TI  - Reduced transcriptional activity in the p53 pathway of senescent cells revealed
      by the MDM2 antagonist nutlin-3.
AB  - The p53 tumor suppressor plays a key role in induction and maintenance of
      cellular senescence but p53-regulated response to stress in senescent cells is
      poorly understood. Here, we use the small-molecule MDM2 antagonist, nutlin-3a, to
      selectively activate p53 and probe functionality of the p53 pathway in senescent
      human fibroblasts, WI-38. Our experiments revealed overall reduction in nutlin
      induced transcriptional activity of nine p53 target genes and four p53-regulated
      microRNAs, indicating that not only p53 protein levels but also its ability to
      activate transcription are altered during senescence. Addition of nutlin restored
      doxorubicin-induced p53 protein and transcriptional activity in senescent cells
      to the levels in early passage cells but only partially restored its apoptotic
      activity, suggesting that changes in both upstream and downstream p53 signaling
      during senescence are responsible for attenuated response to genotoxic stress.

PMID- 20157558
TI  - Circadian disruption induced by light-at-night accelerates aging and promotes
      tumorigenesis in rats.
AB  - We evaluated the effect of various light/dark regimens on the survival, life span
      and tumorigenesis in rats. Two hundred eight male and 203 females LIO rats were
      subdivided into 4 groups and kept at various light/dark regimens: standard 12:12
      light/dark (LD); natural lighting of the North-West of Russia (NL); constant
      light (LL), and constant darkness (DD) since the age of 25 days until natural
      death. We found that exposure to NL and LL regimens accelerated development of
      metabolic syndrome and spontaneous tumorigenesis, shortened life span both in
      male and females rats as compared to the standard LD regimen. We conclude that
      circadian disruption induced by light-at-night accelerates aging and promotes
      tumorigenesis in rats. This observation supports the conclusion of the
      International Agency Research on Cancer that shift-work that involves circadian
      disruption is probably carcinogenic to humans.

PMID- 20157559
TI  - TAp63: The fountain of youth.
AB  - The mechanisms controlling organismal aging have yet to be clearly defined. In
      our recent paper [1], we revealed thatTAp63, the p53 family member, is a critical
      gene in preventing organismal aging by controlling the maintenance of dermal and
      epidermal precursor and stem cells critical for wound healing and hair growth. In
      the absence of TAp63, dermal stem cells (skin-derived precursors or SKPs) in
      young mice are hyperproliferative. As early as one month of age, SKPs and
      epidermal precursor cells exhibit signs of premature aging including a marked
      increase in senescence, DNA damage, and genomic instability resulting in an
      exhaustion of these cells and an overall acceleration in aging. Here, we discuss
      our findings and its relevance to longevity, regenerative medicine, and
      tumorigenesis.

PMID- 20157560
TI  - Dopamine suppresses octopamine signaling in C. elegans: possible involvement of
      dopamine in the regulation of lifespan.
AB  - Amine neurotransmitters, such as dopamine, serotonin, and noradrenaline, play
      important roles in the modulation of behaviors and metabolism of animals. InC.
      elegans, it has been shown that serotonin and octopamine, an invertebrate
      equivalent of noradrenaline, also regulate lifespan through a mechanism related
      to food deprivation-mediated lifespan extension. We have shown recently that
      dopamine signaling, activated by the tactile perception of food, suppresses
      octopamine signaling and that the cessation of dopamine signaling in the absence
      of food leads to activation of octopamine signaling. Here, we discuss the
      apparent conservation of neural and molecular mechanisms for dopamine regulation
      of octopamine/noradrenaline signaling and a possible role for dopamine in
      lifespan regulation.

PMID- 20157561
TI  - Macronutrient balance and lifespan.
AB  - Dietary restriction (DR) without malnutrition is widely regarded to be a
      universal mechanism for prolonging lifespan. It is generally believed that the
      benefits of DR arise from eating fewer calories (termed caloric restriction, CR).
      Here we argue that, rather than calories, the key determinant of the relationship
      between diet and longevity is the balance of protein to non-protein energy
      ingested. This ratio affects not only lifespan, but also total energy intake,
      metabolism, immunity and the likelihood of developing obesity and associated
      metabolic disorders. Among various possible mechanisms linking macronutrient
      balance to lifespan, the nexus between the TOR and AMPK signaling pathways is
      emerging as a central coordinator.

PMID- 20157562
TI  - Ubiquitin ligases join the field of dietary restriction in C.elegans.

PMID- 20157563
TI  - Could stress granules be involved in age-related diseases?

PMID- 20157564
TI  - Mitochondrial superoxide: a key player in Alzheimer's disease.

PMID- 20157565
TI  - Coupling transcriptional and post-transcriptional miRNA regulation in the control
      of cell fate.
AB  - miRNAs function as a critical regulatory layer in development, differentiation,
      and the maintenance of cell fate. Depletion of miRNAs from embryonic stem cells
      impairs their differentiation capacity. Total elimination of miRNAs leads to
      premature senescence in normal cells and tissues through activation of the DNA
      damage checkpoint, whereas ablation of miRNAs in cancer cell lines results in an
      opposite effect, enhancing their tumorigenic potential. Here we compile evidence
      from the literature that point at miRNAs as key players in the maintenance of
      genomic integrity and proper cell fate. There is an apparent gap between our
      understanding of the subtle way by which miRNAs modulate protein levels, and
      their profound impact on cell fate. We propose that examining miRNAs in the
      context of the regulatory transcriptional and post-transcriptional networks they
      are embedded in may provide a broader view of their role in controlling cell
      fate.

PMID- 20157566
TI  - Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in
      skeletal muscle.
AB  - SIRT3 is a member of the sirtuin family of NAD(+)-dependent deacetylases, which
      is localized to the mitochondria and is enriched in kidney, brown adipose tissue,
      heart, and other metabolically active tissues. We report here that SIRT3 responds
      dynamically to both exercise and nutritional signals in skeletal muscle to
      coordinate downstream molecular responses. We show that exercise training
      increases SIRT3 expression as well as associated CREB phosphorylation and PGC
      1alpha up-regulation. Furthermore, we show that SIRT3 is more highly expressed in
      slow oxidative type I soleus muscle compared to fast type II extensor digitorum
      longus or gastrocnemius muscles. Additionally, we find that SIRT3 protein levels
      in skeletal muscle are sensitive to diet, for SIRT3 expression increases by
      fasting and caloric restriction, yet it is decreased by high-fat diet.
      Interestingly, the caloric restriction regimen also leads to phospho-activation
      of AMPK in muscle. Conversely in SIRT3 knockout mice, we find that the
      phosphorylation of both AMPK and CREB and the expression of PGC-1alpha are down
      regulated, suggesting that these key cellular factors may be important components
      of SIRT3-mediated biological signals in vivo.

PMID- 20157567
TI  - Dermal fibroblasts from long-lived Ames dwarf mice maintain their in vivo
      resistance to mitochondrial generated reactive oxygen species (ROS).
AB  - Activation of p38 MAPK by ROS involves dissociation of an inactive, reduced
      thioredoxin-ASK1 complex [(SH)(2)Trx-ASK1]. Release of ASK1 activates its kinase
      activity thus stimulating the p38 MAPK pathway. The level of p38 MAPK activity
      is, therefore, regulated by the balance of free vs. bound ASK1. Longevity of Ames
      dwarf mice is attributed to their resistance to oxidative stress. The levels of
      (SH)(2) Trx-ASK1 are more abundant in young and old dwarf mice compared to their
      age-matched controls suggesting that the levels of this complex may play a role
      in their resistance to oxidative stress. In these studies we demonstrate that
      dermal fibroblasts from these long-lived mice exhibit (a) higher levels of
      (SH)(2)Trx-ASK1 that correlate with their resistance to ROS generated by
      inhibitors of electron transport chain complexes CI (rotenone), CII (3
      nitropropionic acid), CIII, (antimycin A), and H(2)O(2)-mediated activation of
      p38 MAPK, and (b) maintain their in vivo resistance to ROS generated by 3NPA. We
      propose that elevated levels of (SH)(2)Trx-ASK1 play a role in conferring
      resistance to mitochondrial generated oxidative stress and decreased endogenous
      ROS which are characteristics of longevity determination.

PMID- 20157568
TI  - The mRNA decay factor tristetraprolin (TTP) induces senescence in human
      papillomavirus-transformed cervical cancer cells by targeting E6-AP ubiquitin
      ligase.
AB  - The RNA-binding protein tristetraprolin (TTP) regulates expression of many cancer
      associated and proinflammatory factors through binding AU-rich elements (ARE) in
      the 3'-untranslated region (3'UTR) and facilitating rapid mRNA decay. Here we
      report on the ability of TTP to act in an anti-proliferative capacity in HPV18
      positive HeLa cells by inducing senescence. HeLa cells maintain a dormant p53
      pathway and elevated telomerase activity resulting from HPV-mediated
      transformation, whereas TTP expression counteracted this effect by stabilizing
      p53 protein and inhibiting hTERT expression. Presence of TTP did not alter E6 and
      E7 viral mRNA levels indicating that these are not TTP targets. It was found that
      TTP promoted rapid mRNA decay of the cellular ubiquitin ligase E6-associated
      protein (E6-AP). RNA-binding studies demonstrated TTP and E6-AP mRNA interaction
      and deletion of the E6-AP mRNA ARE-containing 3'UTR imparts resistance to TTP
      mediated downregulation. Similar results were obtained with high-risk HPV16
      positive cells that employ the E6-AP pathway to control p53 and hTERT levels.
      Furthermore, loss of TTP expression was consistently observed in cervical cancer
      tissue compared to normal tissue. These findings demonstrate the ability of TTP
      to act as a tumor suppressor by inhibiting the E6-AP pathway and indicate TTP
      loss to be a critical event during HPV-mediated carcinogenesis.

PMID- 20157569
TI  - Molecular basis for an attenuated mitochondrial adaptive plasticity in aged
      skeletal muscle.
AB  - Our intent was to investigate the mechanisms driving the adaptive potential of
      subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in young (6 mo) and
      senescent (36 mo) animals in response to a potent stimulus for organelle
      biogenesis. We employed chronic electrical stimulation (10 Hz, 3 h/day, 7 days)
      to induce contractile activity of skeletal muscle in 6 and 36 mo F344XBN rats.
      Subsequent to chronic activity, acute stimulation (1 Hz, 5 min) in situ revealed
      greater fatigue resistance in both age groups. However, the improvement in
      endurance was significantly greater in the young, compared to the old animals.
      Chronic muscle use also augmented SS and IMF mitochondrial volume to a greater
      extent in young muscle. The molecular basis for the diminished organelle
      expansion in aged muscle was due, in part, to the collective attenuation of the
      chronic stimulation-evoked increase in regulatory proteins involved in mediating
      mitochondrial protein import and biogenesis. Furthermore, adaptations in
      mitochondrial function were also blunted in old animals. However, chronic
      contractile activity evoked greater reductions in mitochondrially-mediated
      proapoptotic signaling in aged muscle. Thus, mitochondrial plasticity is retained
      in aged animals, however the magnitude of the changes are less compared to young
      animals due to attenuated molecular processes regulating organelle biogenesis.

PMID- 20157570
TI  - Caveolin-1, cellular senescence and pulmonary emphysema.
AB  - Caveolae are vesicular invaginations of the plasma membrane. Caveolin-1 is the
      structural protein component of caveolae. Caveolin-1 participates in signal
      transduction processes by acting as a scaffolding protein that concentrates,
      organizes and functional regulates signaling molecules within caveolar membranes.
      Cigarette smoke, a source of oxidants, is an environmental hazard that causes
      pulmonary emphysema. Recently, we reported that the development of cigarette
      smoking-induced pulmonary emphysema was inhibited in caveolin-1 null mice, which
      do not express caveolin-1. We demonstrated that lack of caveolin-1 expression in
      lung fibroblasts dramatically inhibited premature senescence induced by oxidants
      contained in cigarette smoke. Mechanistically, we uncovered that premature
      senescence of lung fibroblasts induced by oxidative stress occurred through
      activation of an ataxia telangiectasia-mutated (ATM)/p53-depedent pathway
      following sequestration of the catalytic subunit of protein phosphatase 2A (PP2A
      C), an inhibitor of ATM, by caveolin-1 into caveolar membranes. We propose
      caveolin-1 as a key player of a novel signaling pathway that links cigarette
      smoke to premature senescence of lung fibroblasts and development of pulmonary
      emphysema.

PMID- 20157571
TI  - p53, sex, and aging: lessons from the fruit fly.

PMID- 20157572
TI  - It's all about balance: p53 and aging.

PMID- 20157573
TI  - Ionizing radiation and aging: rejuvenating an old idea.
AB  - This paper reviews the contemporary evidence that radiation can accelerate aging,
      degenerative health effects and mortality. Around the 1960s, the idea that
      ionizing radiation caused premature aging was dismissed as the radiation-induced
      health effects appeared to be virtually confined to neoplasms. More recently,
      radiation has become associated with a much wider spectrum of age-related
      diseases, including cardiovascular disease; although some diseases of old age,
      such as diabetes, are notably absent as a radiation risk. On the basis of recent
      research, is there a stronger case today to be made linking radiation and aging?
      Comparison is made between the now-known biological mechanisms of aging and those
      of radiation, including oxidative stress, chromosomal damage, apoptosis, stem
      cell exhaustion and inflammation. The association between radiation effects and
      the free-radical theory of aging as the causative hypothesis seems to be more
      compelling than that between radiation and the nutrient-sensing TOR pathway.
      Premature aging has been assessed by biomarkers in calorie restriction studies;
      yet, biomarkers such as telomere erosion and p16(INK4a) are ambiguous for
      radiation-induced aging. Some animal studies suggest low dose radiation may even
      demonstrate hormesis health benefits. Regardless, there is virtually no support
      for a life span extending hypothesis for A-bomb survivors and other exposed
      subjects.

PMID- 20157574
TI  - Drosophila melanogaster p53 has developmental stage-specific and sex-specific
      effects on adult life span indicative of sexual antagonistic pleiotropy.
AB  - Truncated and mutant forms ofp53 affect life span in Drosophila, nematodes and
      mice, however the role of wild-type p53 in aging remains unclear. Here
      conditional over-expression of both wild-type and mutant p53 transgenes indicated
      that, in adult flies, p53 limits life span in females but favors life span in
      males. In contrast, during larval development, moderate over-expression of p53
      produced both male and female adults with increased life span. Mutations of the
      endogenous p53 gene also had sex-specific effects on life span under control and
      stress conditions: null mutation of p53 increased life span in females, and had
      smaller, more variable effects in males. These developmental stage-specific and
      sex-specific effects of p53 on adult life span are consistent with a sexual
      antagonistic pleiotropy model.

PMID- 20157575
TI  - The circadian clock gene period extends healthspan in aging Drosophila
      melanogaster.
AB  - There is increasing evidence that aging is affected by biological (circadian)
      clocks - the internal mechanisms that coordinate daily changes in gene
      expression, physiological functions and behavior with external day/night cycles.
      Recent data suggest that disruption of the mammalian circadian clock results in
      accelerated aging and increased age-related pathologies such as cancer; however,
      the links between loss of daily rhythms and aging are not understood. We sought
      to determine whether disruption of the circadian clock affects lifespan and
      healthspan in the model organism Drosophila melanogaster. We examined effects of
      a null mutation in the circadian clock gene period (per(01)) on the fly
      healthspan by challenging aging flies with short-term oxidative stress (24h
      hyperoxia) and investigating their response in terms of mortality hazard, levels
      of oxidative damage, and functional senescence. Exposure to 24h hyperoxia during
      middle age significantly shortened the life expectancy in per(01) but not in
      control flies. This homeostatic challenge also led to significantly higher
      accumulation of oxidative damage in per(01) flies compared to controls. In
      addition, aging per(01) flies showed accelerated functional decline, such as
      lower climbing ability and increased neuronal degeneration compared to age
      matched controls. Together, these data suggest that impaired stress defense
      pathways may contribute to accelerated aging in the per mutant. In addition, we
      show that the expression of per gene declines in old wild type flies, suggesting
      that the circadian regulatory network becomes impaired with age.

PMID- 20157576
TI  - Paradoxical down-regulation of p16 mRNA with advancing age in acute myeloid
      leukemia.
AB  - Aging is generally considered to be the consequence of stem cell attrition caused
      by the activity of tumor suppressor pathways that censor potentially malignant
      clones by eliciting apoptosis or senescence. An important effector of aging is
      the cyclindependent kinase inhibitor p16(INK4a), which is also a known suppressor
      of cancer. The expression of p16(INK4a) is very low or absent in young organisms
      but increases with advancing age. We recently showed that, unlike healthy cells,
      acute myeloid leukemia (AML) derived blasts show a down-regulation of p16(INK4a)
      mRNA with increasing age. Based on this observation we hypothesize that
      suppression of defense mechanisms which protect older cells against cellular and
      DNA damage might facilitate oncogenesis in older individuals.

PMID- 20157577
TI  - Leptin-dependent co-regulation of bone and energy metabolism.
AB  - The adipocyte-derived hormone leptin inhibits appetite and bone mass accrual. To
      fulfill these two functions leptin requires the integrity of hypothalamic neurons
      but not the expression of its receptor, ObRb on these neurons. These results
      suggested that leptin acts first elsewhere in the brain to mediate these
      functions. However, this neuroanatomical site of leptin action in the brain
      remained elusive. Recent mouse genetic, electrophysiological and neuroanatomical
      studies provide evidence that leptin inhibits appetite and bone mass accrual
      through a two-step pathway: it decreases synthesis and the release by brainstem
      neurons of serotonin that in turn targets hypothalamic neurons to regulate
      appetite and bone mass accrual.

PMID- 20157578
TI  - Surviving in the cold: yeast mutants with extended hibernating lifespan are
      oxidant sensitive.
AB  - Metabolic activity generates oxidizing molecules throughout life, but it is still
      debated if the resulting damage of macromolecules is a causality, or consequence,
      of the aging process. This problem demands for studying growth- and longevity
      phenotypes separately. Here, we assayed a complete collection of haploid
      Saccharomyces cerevisiae knock-out strains for their capacity to endure long
      periods at low metabolic rates. Deletion of 93 genes, predominantly factors of
      primary metabolism, allowed yeast to survive for more than 58 months in the cold.
      The majority of these deletion strains were not resistant against oxidants or
      reductants, but many were hypersensitive. Hence, survival at low metabolic rates
      has limiting genetic components, and correlates with stress resistance inversely.
      Indeed, maintaining the energy consuming anti-oxidative machinery seems to be
      disadvantageous under coldroom conditions.

PMID- 20157579
TI  - Autophagy mediates pharmacological lifespan extension by spermidine and
      resveratrol.
AB  - Although autophagy has widely been conceived as a self-destructive mechanism that
      causes cell death, accumulating evidence suggests that autophagy usually mediates
      cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed
      cells. Recent evidence produced by our groups demonstrates that autophagy is also
      involved in pharmacological manipulations that increase longevity. Exogenous
      supply of the polyamine spermidine can prolong the lifespan of (while inducing
      autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger
      autophagy in cells from different organisms, extend lifespan in nematodes, and
      ameliorate the fitness of human cells undergoing metabolic stress. These
      beneficial effects are lost when essential autophagy modulators are genetically
      or pharmacologically inactivated, indicating that autophagy is required for the
      cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic
      and functional studies indicate that spermidine inhibits histone acetylases,
      while resveratrol activates the histone deacetylase Sirtuin 1 to confer
      cytoprotection/longevity. Although it remains elusive whether the same histones
      (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets
      of spermidine and resveratrol, these results point to an essential role of
      protein hypoacetylation in autophagy control and in the regulation of longevity.

PMID- 20157580
TI  - Aged mouse ovaries possess rare premeiotic germ cells that can generate oocytes
      following transplantation into a young host environment.
AB  - Of all the major organ systems in the body, the ovaries of females are the first
      to exhibit impaired function with advancing age. Until recently, traditional
      thinking was that female mammals are provided with a non-renewable pool of oocyte
      containing follicles at birth that are depleted during postnatal life to
      exhaustion, driving ovarian failure. However, a growing body of evidence,
      including the isolation of germline stem cells (GSC) from adult mouse ovaries
      that produce developmentally-competent oocytes, has challenged this belief. In
      addition, rare germline stem-like cells capable of generating oocytes in vitro
      that undergo parthenogenesis to form blastocyst-like structures have recently
      been identified in postmenopausal human ovaries. Here we show that the germline
      specific meiosis-commitment genes,Stimulated by retinoic acid gene 8 (Stra8) and
      Deleted in azoospermia-like (Dazl), are highly expressed in aged mouse ovaries.
      However, histological and marker analyses fail to demonstrate the presence of
      oocytes, supporting that Stra8 and Dazl are expressed in premeiotic germ cells
      that do not undergo further differentiation. Through the use of aged germline
      specific GFP-expressing transgenic mice, we further show that these germ cells
      can generate GFP-positive oocytes that co-express the primordial oocyte marker
      NOBOX and form follicles when grafted into young adult wild-type female hosts.
      Thus, aged mouse ovaries possess a rare population of premeiotic germ cells that
      retain the capacity to form oocytes if exposed to a young host environment.

PMID- 20157581
TI  - Antioxidant N-acetyl-L-cysteine ameliorates symptoms of premature aging
      associated with the deficiency of the circadian protein BMAL1.
AB  - Deficiency of the circadian clock protein BMAL1 leads to premature aging and
      increased levels of reactivate oxygen species in several tissues of mice. In
      order to investigate the role of oxidative stress in accelerated aging and
      development of age-related pathologies, we continuously administered the
      antioxidant N-acetyl-L-cysteine toBmal1-deficient mice through their entire
      lifespan by supplementing drinking water. We found that the life long treatment
      with antioxidant significantly increased average and maximal lifespan and reduced
      the rate of age-dependent weight loss and development of cataracts. At the same
      time, it had no effect on time of onset and severity of other age-related
      pathologies characteristic of Bmal1-/- mice, such as joint ossification, reduced
      hair regrowth and sarcopenia. We conclude that chronic oxidative stress affects
      longevity and contributes to the development of at least some age-associated
      pathology, although ROS-independent mechanisms may also play a role. Our
      bioinformatics analysis identified the presence of a conservative E box element
      in the promoter regions of several genes encoding major antioxidant enzymes. We
      speculate that BMAL1 controls antioxidant defense by regulating the expression of
      major antioxidant enzymes.

PMID- 20157582
TI  - Fasting and cancer treatment in humans: A case series report.
AB  - Short-term fasting (48 hours) was shown to be effective in protecting normal
      cells and mice but not cancer cells against high dose chemotherapy, termed
      Differential Stress Resistance (DSR), but the feasibility and effect of fasting
      in cancer patients undergoing chemotherapy is unknown. Here we describe 10 cases
      in which patients diagnosed with a variety of malignancies had voluntarily fasted
      prior to (48-140 hours) and/or following (5-56 hours) chemotherapy. None of these
      patients, who received an average of 4 cycles of various chemotherapy drugs in
      combination with fasting, reported significant side effects caused by the fasting
      itself other than hunger and lightheadedness. Chemotherapy associated toxicity
      was graded according to the Common Terminology Criteria for Adverse Events
      (CTCAE) of the National Cancer Institute (NCI). The six patients who underwent
      chemotherapy with or without fasting reported a reduction in fatigue, weakness,
      and gastrointestinal side effects while fasting. In those patients whose cancer
      progression could be assessed, fasting did not prevent the chemotherapy-induced
      reduction of tumor volume or tumor markers. Although the 10 cases presented here
      suggest that fasting in combination with chemotherapy is feasible, safe, and has
      the potential to ameliorate side effects caused by chemotherapies, they are not
      meant to establish practice guidelines for patients undergoing chemotherapy. Only
      controlled-randomized clinical trials will determine the effect of fasting on
      clinical outcomes including quality of life and therapeutic index.

PMID- 20157583
TI  - Quantifying pharmacologic suppression of cellular senescence: prevention of
      cellular hypertrophy versus preservation of proliferative potential.
AB  - Development of agents that suppress aging (aging suppressants) requires
      quantification of cellular senescence. Cellular senescence in vitro is
      characterized by a large cell morphology and permanent loss of proliferative
      potential. When HT-1080 cells were arrested by p21, they continued to grow
      exponentially in size and became hypertrophic with a 15-fold increase in the
      protein content per cell. These changes were mirrored by accumulation of GFP
      (driven by CMV promoter) per cell, which also served as a marker of cellular
      hypertrophy. Preservation of proliferative potential (competence) was measured by
      an increase in live cell number, when p21 was switched off. While modestly
      decreasing hypertrophy in p21-arresrted cells, rapamycin considerably preserved
      competence, converting senescence into quiescence. Preservation of proliferative
      potential (competence) correlated with inhibition of S6 phosphorylation by
      rapamycin. When p21 was switched off, competent cells, by resuming proliferation,
      became progressively less hypertrophic. Preservation of proliferative potential
      is a sensitive and quantitative measure of suppression of mTOR-driven senescence.

PMID- 20157584
TI  - The central role of chromatin maintenance in aging.
AB  - Epigenetic regulation of chromatin and the DNA damage response are now well
      appreciated key players in human aging. What contributions chromatin and DAN
      repair make to aging, whether they are causal, and how these relate to other
      aging pathways, however, is unclear. Novel insights into the aging-related
      molecular mechanisms that link chromatin and DNA damage repair have recently been
      gained by studying models of both premature and physiological aging. Here we
      discuss these findings and we propose a broad framework for the role of chromatin
      in aging to reconcile apparently contradicting evidence obtained in various
      experimental systems.

PMID- 20157585
TI  - Role of FGF19 induced FGFR4 activation in the regulation of glucose homeostasis.
AB  - FGF19, FGF21, and FGF23 form a unique subfamily of fibroblast growth factors.
      Because they contain intra-molecular disulfide bonds and show reduced affinity
      toward heparan sulfate located in the extracellular space, it is thought that, in
      contrast to other FGFs, they function as endocrine hormones. FGF23 and its co
      receptor alphaKlotho are involved in the control of aging, but it is not known if
      the same holds true for FGF19, which can also signal through alphaKlotho.
      However, considerable evidence supports a role for FGF19 in controlling various
      aspects of metabolism. We have recently fully characterized FGF19/FGFR/co-factor
      interactions and signaling, and in the current manuscript discuss the
      contribution of the FGF19/FGFR4 axis to bile acid and glucose regulation.

PMID- 20157586
TI  - The mtDNA mutator mouse: Dissecting mitochondrial involvement in aging.
AB  - The role of mtDNA mutations in aging has been intensely debated because of their
      low abundance and correlative connection with aging. The creation of mtDNA
      mutator mice provided the first evidence that somatic mtDNA mutations have the
      capacity to cause a variety of aging phenotypes in mammals, and they do so
      without inducing ROS production or increasing oxidative stress. We have recently
      provided evidence that the accumulation of point mutations in mtDNA leads to the
      synthesis of respiratory chain subunits with amino acid substitutions that impair
      complex stability in mtDNA mutator mice. Furthermore, we have demonstrated that
      the point mutations cause progressive respiratory chain deficiency, which, we
      propose, leads to premature aging. These results have been challenged by another
      group working on a similar model, who argues that the point mutations in mtDNA we
      found at very high levels in mtDNA mutator mice do not cause the phenotype.
      Instead, they argue that circular mtDNA molecules with large deletions, are the
      culprit. This intense debate about molecular mechanism of mitochondrial
      dysfunction that is causing progeroid phenotypes in the mtDNA mutator mice is the
      main topic of this research perspective.

PMID- 20157587
TI  - Young adult donor bone marrow infusions into female mice postpone age-related
      reproductive failure and improve offspring survival.
AB  - The female reproductive axis is the first major organ system of the body to fail
      with advancing age. In addition to a permanent cessation of fertile potential,
      the loss of cyclic ovarian function in humans heralds the onset of menopause,
      which in turn underlies the emergence of a diverse spectrum of health issues in
      aging women. Recently, it was reported that bone marrow (BM) transplantation
      (BMT) into adult female mice conditioned a week earlier with highly cytotoxic
      drugs rescues ovarian function and fertility. Herein we show in mice receiving no
      prior conditioning regimen that once-monthly infusions of BM-derived cells
      retrieved from young adult female donors bearing an enhanced green fluorescent
      protein (EGFP) transgene sustain the fertile potential of aging wild-type females
      long past their time of normal reproductive senescence. The fertility-promoting
      effects of female donor BM are observed regardless whether the infusions are
      initiated in young adult or middle-aged females. Although the mechanism by which
      BM infusions benefit the reproductive performance of aging females remains to be
      elucidated, the absence of EGFP-expressing offspring suggests that it does not
      depend on development of mature eggs derived from germline-committed cells in the
      donor marrow. However, donor BM-derived somatic cells accumulate in the
      recipients, indicating efficient donor cell engraftment without prior
      conditioning. These findings provide a strong impetus to further explore
      development of adult stem cell-based technologies to safely extend function of
      the female reproductive axis into advanced age without the need for toxic pre
      conditioning protocols routinely used in other models of stem cell delivery.

PMID- 20157588
TI  - Dual regulation of TERT activity through transcription and splicing by
      DeltaNP63alpha.
AB  - P53 homolog p63 was shown to play a role in premature ageing phenotype found in
      mouse models through regulation of the replicative senescence. We previously
      showed that the forced DeltaNp63alpha expression decreased the SIRT1 protein
      levels, and induced the replicative senescence of human keratinocytes, while the
      ectopic SIRT1 expression decreased the senescence. Using the DeltaNp63alpha
      overexpressing and p63-/+ heterozygous mice, we found that DeltaNp63alpha induced
      the mTERT promoter activation through the down regulation of the SIRT1 protein
      levels, inactivation of p53 deacetylation, decrease of the p53/Sp1 protein
      protein interaction, and the overall induction of mTERT transcription regulation.
      In the same time, by a forming of protein-protein complexes with the ABBP1,
      DeltaNp63alpha induced the mTERT RNA splicing leading to an increasing expression
      of spliced mTERT isoforms playing a role of dominant-negative inhibitors of mTERT
      activity and therefore decreasing the levels of TERT activity in mouse epidermal
      keratinocytes. The overall effect of the DeltaNp63alpha overexpression resulted
      in decrease in telomerase activity and increase in replicative senescence
      observed in mouse keratinocytes. This dual molecular mechanism of telomerase
      regulation might underline the previously shown effect of DeltaNp63alpha on
      premature ageing phenotype.

PMID- 20157590
TI  - Aging: past, present and future.

PMID- 20157589
TI  - Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid
      peroxidation product 4-hydroxynonenal (4-HNE).
AB  - Deposition and mobilization of fat in an organism are tightly controlled by
      multiple levels of endocrine and neuroendocrine regulation. Because these
      hormonal mechanisms ultimately act by affecting biochemical reactions of fat
      synthesis or utilization, obesity could be also modulated by altering directly
      the underlying lipid biochemistry. We have previously shown that genetically
      modified mice with an elevated level of the lipid peroxidation product 4-HNE
      become obese. We now demonstrate that the process is phylogenetically conserved
      and thus likely to be universal. In the nematode C. elegans, disruption of either
      conjugation or oxidation of 4-HNE leads to fat accumulation, whereas augmentation
      of 4-HNE conjugation results in a lean phenotype. Moreover, direct treatment of
      C. elegans with synthetic 4-HNE causes increased lipid storage, directly
      demonstrating a causative role of 4-HNE. The postulated mechanism, which involves
      modulation of acetyl-CoA carboxylase activity, could contribute to the triggering
      and maintenance of the obese phenotype on a purely metabolic level.

PMID- 20157591
TI  - Longevity regulation in flies: a role for p53.

PMID- 20157592
TI  - Breathing lessons: Tor tackles the mitochondria.

PMID- 20157593
TI  - Sirtuins at the breaking point: SIRT6 in DNA repair.

PMID- 20157594
TI  - SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand
      break repair.
AB  - The Sir2 chromatin regulatory factor links maintenance of genomic stability to
      life span extension in yeast. The mammalian Sir2 family member SIRT6 has been
      proposed to have analogous functions, because SIRT6-deficiency leads to shortened
      life span and an aging-like degenerative phenotype in mice, and SIRT6 knockout
      cells exhibit genomic instability and DNA damage hypersensitivity. However, the
      molecular mechanisms underlying these defects are not fully understood. Here, we
      show that SIRT6 forms a macromolecular complex with the DNA double-strand break
      (DSB) repair factor DNA-PK (DNA-dependent protein kinase) and promotes DNA DSB
      repair. In response to DSBs, SIRT6 associates dynamically with chromatin and is
      necessary for an acute decrease in global cellular acetylation levels on histone
      H3 Lysine 9. Moreover, SIRT6 is required for mobilization of the DNA-PK catalytic
      subunit (DNA-PKcs) to chromatin in response to DNA damage and stabilizes DNA-PKcs
      at chromatin adjacent to an induced site-specific DSB. Abrogation of these SIRT6
      activities leads to impaired resolution of DSBs. Together, these findings
      elucidate a mechanism whereby regulation of dynamic interaction of a DNA repair
      factor with chromatin impacts on the efficiency of repair, and establish a link
      between chromatin regulation, DNA repair, and a mammalian Sir2 factor.

PMID- 20157595
TI  - Extension of chronological life span by reduced TOR signaling requires down
      regulation of Sch9p and involves increased mitochondrial OXPHOS complex density.
AB  - The nutrient-sensing target of rapamycin (TOR) pathway appears to have a
      conserved role in regulating life span. This signaling network is complex, with
      many downstream physiological outputs, and thus the mechanisms underlying its age
      related effects have not been elucidated fully. We demonstrated previously that
      reduced TOR signaling (intor1Delta strains) extends yeast chronological life span
      (CLS) by increasing mitochondrial oxygen consumption, in part, by up-regulating
      translation of mtDNA-encoded oxidative phosphorylation (OXPHOS) subunits. Here,
      we have examined in greater detail how TOR signaling influences mitochondrial
      function and CLS and the role of the Sch9p kinase in the TOR-mitochondria
      pathway. As is the case for oxygen consumption, mitochondrial translation is
      elevated in tor1Delta strains only during active growth and early stationary
      phase growth points. This is accompanied by a corresponding increase in the
      abundance of both mtDNA-encoded and nucleus-encoded OXPHOS subunits per
      mitochondrial mass. However, this increased OXPHOS complex density is not
      associated with more mitochondria/cell or cellular ATP and leads to an overall
      decrease in membrane potential, suggesting that TOR signaling may influence
      respiration uncoupling. Finally, we document that the Sch9p kinase is a key
      downstream effector of OXPHOS, ROS and CLS in the TOR-mitochondria pathway.
      Altogether, our results demonstrate that TOR signaling has a global role in
      regulating mitochondrial proteome dynamics and function that is important for its
      role in aging and provide compelling evidence for involvement of a "mitochondrial
      pre-conditioning" effect in CLS determination.

PMID- 20157597
TI  - Post-transcriptional Regulation of NK Cell Activation.
AB  - Natural killer (NK) cells play key roles in innate and adaptive immune defenses.
      NK cell responses are mediated by two major mechanisms: the direct cytolysis of
      target cells, and immune regulation by production of various cytokines. Many
      previous reports show that the complex NK cell activation process requires de
      novo gene expression regulated at both transcriptional and post-transcriptional
      levels. Specialized un-translated regions (UTR) of mRNAs are the main mechanisms
      of post-transcriptional regulation. Analysis of post-transcriptional regulation
      is needed to clearly understand NK cell biology and, furthermore, harness the
      power of NK cells for therapeutic aims. This review summarizes the current
      understanding of mRNA metabolism during NK cell activation, focusing primarily on
      post-transcriptional regulation.

PMID- 20157598
TI  - Regulation of tumor immune surveillance and tumor immune subversion by tgf-Beta.
AB  - Transforming growth factor-beta (TGF-beta) is a highly pleiotropic cytokine
      playing pivotal roles in immune regulation. TGF-beta facilitates tumor cell
      survival and metastasis by targeting multiple cellular components. Focusing on
      its immunosuppressive functions, TGF-beta antagonists have been employed for
      cancer treatment to enhance tumor immunity. TGF-beta antagonists exert anti-tumor
      effects through #1 activating effector cells such as NK cells and cytotoxic
      CD8(+) T cells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3
      making tumor cells visible to immune cells, #4 inhibiting the production of tumor
      growth factors. This review focuses on the effect of TGF-beta on T cells, which
      are differentiated into effector T cells or newly identified tumor-supporting T
      cells.

PMID- 20157599
TI  - Expression and Function of TLR2 on CD4 Versus CD8 T Cells.
AB  - BACKGROUND: Toll-like receptors (TLRs) play a fundamental role in innate immunity
      through their capacity to recognize pathogen-associated molecular patterns. Also,
      TLRs that are expressed in T cells are reported to function as co-stimulatory
      receptors. However, the functional capacity of TLRs on CD4 T and CD8 T cells has
      not been directly compared. Here we compared CD4 and CD8 T cell responses to TLR2
      ligand plus TCR-mediated stimulation. METHODS: TLR2 expression was analyzed on T
      cell subsets under naive and alloantigen-primed conditions. We analyzed the
      effects of TLR2 co-stimulation on proliferation and survival of T cell subsets in
      vitro when stimulated with soluble anti-CD3 in the presence or absence of
      synthetic ligand Pam(3)CSK(4). RESULTS: TLR2 expression on CD8 T cells was
      induced following activation; this expression was much higher than on CD4 T
      cells. Thus, the molecule was constitutively expressed on Listeria-specific
      memory CD8 T cells. Based on these expression levels, proliferation and survival
      were markedly elevated in CD8 T cells in response to the TLR2 co-stimulation by
      Pam(3)CSK(4) compared with those in CD4 T cells. CONCLUSION: Our data show that
      TLR2 co-stimulation is more responsible for proliferation and survival of CD8 T
      cells than for that of CD4 T cells.

PMID- 20157600
TI  - Further Characterization of Activin A-induced IgA Response in Murine B
      Lymphocytes.
AB  - We have recently shown that activin A, a member of TGF-beta superfamily,
      stimulates mouse B cells to express IgA isotype but other isotypes. In the
      present study, we further characterized effects of activin A on B cell growth and
      IgA expression. We found that activin A did not have effect on LPS-stimulated
      cell viability. In parallel, CFSE staining analysis revealed that activin A did
      not alter cell division. An increase of IgA secretion by activin A was completely
      abrogated by anti-activin A Ab but not by anti-TGFbeta1 Ab. In the same
      conditions, no other isotypes are significantly affected by each antibody
      treatment. Finally, activin A, as similar to TGF-beta1, increased IgA secretion
      by mesenteric lymph node cells. These results suggest that activin A can
      specifically stimulate IgA response, independent of TGF-beta in the gut.

PMID- 20157601
TI  - Characterization of a Novel Gene in the Extended MHC Region of Mouse, NG29/Cd320,
      a Homolog of the Human CD320.
AB  - BACKGROUND: The MHC region of the chromosome contains a lot of genes involved in
      immune responses. Here we have investigated the mouse NG29/Cd320 gene in the
      centrometrically extended MHC region of chromosome 17. METHODS: We cloned the
      NG29 gene by RT-PCR and confirmed the tissue distribution of its gene expression
      by northern blot hybridization. We generated the NG29 gene expression constructs
      and polyclonal antibody against the NG29 protein to perform the
      immunofluorescence, immunoprecipitation and flow cytometric analysis. RESULTS:
      The murine NG29 gene and its human homologue, the CD320/8D6 gene, were similar in
      the gene structure and tissue expression patterns. We cloned the NG29 gene and
      confirmed its expression in plasma membrane and intracellular compartments by
      transfecting its expresssion constructs into HEK 293T cells. The
      immunoprecipitation studies with rabbit polyclonal antibody raised against the
      NG29-NusA fusion protein indicated that NG29 protein was a glycoprotein of about
      45 kDa size. A flow cytometric analysis also showed the NG29 expression on the
      surface of Raw 264.7 macrophage cell line. CONCLUSION: These findings suggested
      that NG29 gene in mouse extended MHC class II region was the orthologue of human
      CD320 gene even though human CD320/8D6 gene was located in non-MHC region,
      chromosome 19p13.

PMID- 20157602
TI  - The prospects of vitamin C in cancer therapy.
AB  - Ascorbate (vitamin C) is a cofactor for a number of metabolic enzymes and is an
      indisputable essential vitamin C for humans. However, the potential of ascorbate
      as an anticancer agent has been a topic of controversy. A number of previous
      reports have addressed both positive aspects and limitations of ascorbate in
      cancer therapy. In this review, we briefly summarize the potential antitumor
      effects of ascorbate and its prospects for clinical use.

PMID- 20157603
TI  - Inhibition of leukocyte adhesion by developmental endothelial locus-1 (del-1).
AB  - The leukocyte adhesion to endothelium is pivotal in leukocyte recruitment which
      takes place during inflammatory, autoimmune and infectious conditions. The
      interaction between leukocytes and endothelium requires an array of adhesion
      molecules expressed on leukocytes and endothelial cells, thereby promoting
      leukocyte recruitment into sites of inflammation and tissue injury. Intervention
      with the adhesion molecules provides a platform for development of anti
      inflammatory therapeutics. This review will focus on developmental endothelial
      locus-1 (Del-1), an endogenous inhibitor of leukocyte adhesion.

PMID- 20157604
TI  - Tumor Therapy Applying Membrane-bound Form of Cytokines.
AB  - Tumor therapy using cytokines has been developed for last two decades. Several
      recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer
      have been in clinical trials, but several side effects hamper routine clinical
      applications. Many cytokines are originally expressed as membrane-bound form and
      then processed to secretory form exerting paracrine effects. Though functional
      differences of these two types of cytokines are elusive yet, the membrane-bound
      form of cytokine may exert its effects on restricted target cells as a
      juxtacrine, which are in physical contacts. With the efforts to improve antitumor
      activities of cytokines in cancer patients, developing new strategies to
      alleviate life-threatening side effects became an inevitable goal of tumor
      immunologists. Among these, tumor cell vaccines expressing cytokines as membrane
      bound form on tumor cell surface have been developed by genetic engineering
      techniques with the hope of selective stimulation of the target cells that are in
      cell-to-cell contacts. In this review, recent progress of tumor cell vaccines
      expressing membrane-bound form of cytokines will be discussed.

PMID- 20157605
TI  - Enhancement of DNA Vaccine-induced Immune Responses by Influenza Virus NP Gene.
AB  - DNA immunization induces B and T cell responses to various pathogens and tumors.
      However, these responses are known to be relatively weak and often transient.
      Thus, novel strategies are necessary for enhancing immune responses induced by
      DNA immunization. Here, we demonstrated that co-immunization of influenza virus
      nucleoprotein (NP) gene significantly enhances humoral and cell-mediated
      responses to codelivered antigens in mice. We also found that NP DNA
      coimmunization augments in vivo proliferation of adoptively transferred antigen
      specific CD4 and CD8 T cells, which enhanced protective immunity against tumor
      challenge. Our results suggest that NP DNA can serve as a novel genetic adjuvant
      in cocktail DNA vaccination.

PMID- 20157606
TI  - Prophylactic and Therapeutic Potential of Asp f1 Epitopes in Naive and Sensitized
      BALB/c Mice.
AB  - BACKGROUND: The present study examines a hypothesis that short allergen-derived
      peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards
      a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major
      allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy
      in BALB/c mice. METHODS: To evaluate the prophylactic efficacy, peptides were
      intranasally administered to naive mice and challenged with Afu
      allergens/antigens. For evaluation of therapeutic efficacy, the mice were
      sensitized with Afu-allergens/antigens followed by intranasal administration of
      peptides. The groups were compared for the levels of Afu-specific antibodies in
      sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was
      examined in the lung cell suspensions and lung inflammation was assessed by
      histopathogy. RESULTS: Peptides P1-, P2- and P3 decreased Afu-specific IgE
      (84.5~98.9%) and IgG antibodies (45.7~71.6%) in comparison with Afu-sensitized
      mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu
      specific IgE (76.4~88%) and IgG antibodies (15~54%). Increased IgG2a/IgG1 and IFN
      gamma/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically
      decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased
      inflammatory cells' infiltration in lung tissue comparable to non-challenged
      control. CONCLUSION: Asp f1-derived peptide P1, prophylactically and
      therapeutically administered to Balb/c mice, is effective in regulating allergic
      response to allergens/antigens of Afu, and may be explored for immunotherapy of
      allergic aspergillosis in humans.

PMID- 20157607
TI  - Nitric Oxide Synthesis is Modulated by 1,25-Dihydroxyvitamin D3 and Interferon
      gamma in Human Macrophages after Mycobacterial Infection.
AB  - BACKGROUND: Little information is available the role of Nitric Oxide (NO) in host
      defenses during human tuberculosis (TB) infection. We investigated the modulating
      factor(s) affecting NO synthase (iNOS) induction in human macrophages. METHODS:
      Both iNOS mRNA and protein that regulate the growth of mycobacteria were
      determined using reverase transcriptase-polymerase chain reaction and western
      blot analysis. The upstream signaling pathways were further investigated using
      iNOS specific inhibitors. RESULTS: Here we show that combined treatment with 1,25
      dihydroxyvitamin D3 (1,25-D3) and Interferon (IFN)-gamma synergistically enhanced
      NO synthesis and iNOS expression induced by Mycobacterium tuberculosis (MTB) or
      by its purified protein derivatives in human monocyte-derived macrophages. Both
      the nuclear factor-kappaB and MEK1-ERK1/2 pathways were indispensable in the
      induction of iNOS expression, as shown in toll like receptor 2 stimulation.
      Further, the combined treatment with 1,25-D3 and IFN-gamma was more potent than
      either agent alone in the inhibition of intracellular MTB growth. Notably, this
      enhanced effect was not explained by increased expression of cathelicidin, a
      known antimycobacterial effector of 1,25-D3. CONCLUSION: These data support a key
      role of NO in host defenses against TB and identify novel modulating factors for
      iNOS induction in human macrophages.

PMID- 20157608
TI  - Production of Monoclonal Antibodies Specific to FimA of Porphyromonas gingivalis
      and Their Inhibitory Activity on Bacterial Binding.
AB  - BACKGROUND: The FimA of Porphyromonas gingivalis is a crucial pathogenic
      component of the bacteria and has been implicated as a target for vaccine
      development against the periodontal diseases. METHODS: In this study, the
      purified fimbriae (FimA subunit polymers) protein was used for immunization in
      their native form and B hybridoma clones producing antibodies specific to FimA
      were established. RESULTS: The monoclonal antibodies prepared from selected two
      clones, designated #123 (IgG2b/ kappa) and #265 (IgG1/kappa), displayed different
      patterns of binding activity against the cognate antigen. Both antibodies reacted
      with conformational epitopes expressed by partially dissociated oligomers, but
      not with monomer as elucidated by Western blot analysis. Ascites fluid containing
      the monoclonal antibodies showed the inhibitory activity against P. gingivalis to
      saliva-coated hydroxyapatite beads, an in vitro model for the pellicle-coated
      tooth surface. CONCLUSION: These results suggest that the monoclonal antibodies
      could be used as vaccine material against the periodontal diseases through
      passive immunization.

PMID- 20157610
TI  - Selenium Inhibits Metastasis of Murine Melanoma Cells through the Induction of
      Cell Cycle Arrest and Cell Death.
AB  - BACKGROUND: Melanoma is the most fatal form of skin cancer due to its rapid
      metastasis. Recently, several studies reported that selenium can induce apoptosis
      in melanoma cells. However, the precise mechanism remains to be elucidated. In
      this study, we investigated the effect of selenium on cell proliferation in
      murine melanoma and on tumor growth and metastasis in C57BL/6 mice. METHODS: Cell
      proliferation was measured by MTT assay in selenium-treated melanoma cells. Cell
      cycle distribution was analysized by staining DNA with propidum iodide (PI). mRNA
      and protein expression related to cell cycle arrest was measured by reverse
      transcription PCR and western blot. Tumor growth and metastasis was measured by
      in vivo model. RESULTS: Selenium was suppressed the proliferation of melanoma
      cells in a dose dependent manner. The growth inhibition of melanoma by selenium
      was associated with an arrest of cell cycle distribution at G0/G1 stage. The mRNA
      and protein level of CDK2/CDK4 was suppressed by treatment with selenium in a
      time-dependent manner. In vivo, tumor growth was not suppressed by selenium;
      however tumor metastasis was suppressed by selenium in mouse model. CONCLUSION:
      These results suggest that selenium might be a potent agent to inhibit
      proliferative activity of melanoma cells.

PMID- 20157611
TI  - A new reporter vector system based on flow-cytometry to detect promoter activity.
AB  - In this study, we report the development of a new dual reporter vector system for
      the analysis of promoter activity. This system employs green fluorescence
      emitting protein, EGFP, as a reporter, and uses red fluorescence emitting
      protein, DsRed, as a transfection control in a single vector. The expression of
      those two proteins can be readily detected via flow cytometry in a single
      analysis, with no need for any further manipulation after transfection. As this
      system allows for the simultaneous detection of both the control and reporter
      proteins in the same cells, only transfected cells which express the control
      protein, DsRed, can be subjected to promoter activity analysis, via the gating
      out of all un-transfected cells. This results in a dramatic increase in the
      promoter activity detection sensitivity. This novel reporter vector system should
      prove to be a simple and efficient method for the analysis of promoter activity.

PMID- 20157612
TI  - Tiul1 and TGIF are Involved in Downregulation of TGFbeta1-induced IgA Isotype
      Expression.
AB  - TGF-beta1 is well known to induce Ig germ-line alpha (GLalpha) transcription and
      subsequent IgA isotype class switching recombination (CSR). Homeodomain protein
      TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin
      ligase 1 (Tiul1) are implicated in the negative regulation of TGF-beta signaling.
      In the present study, we investigated the roles of Tiul1 and TGIF in TGFbeta1
      induced IgA CSR. We found that over-expression of Tiul1 decreased TGFbeta1
      induced GLalpha promoter activity and strengthened the inhibitory effect of Smad7
      on the promoter activity. Likewise, overexpression of TGIF also diminished
      GLalpha promoter activity and further strengthened the inhibitory effect of
      Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGFbeta1-induced GLalpha
      expression. In parallel, overexpression of Tiul1 decreased the expression of
      endogenous IgA CSR-predicitive transcripts (GLT(alpha), PST(alpha), and
      CT(alpha)) and TGFbeta1-induced IgA secretion, but not GLT(gamma3) and IgG3
      secretion. Here, over-expressed TGIF further strengthened the inhibitory effect
      of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators
      in TGFbeta1-induced IgA isotype expression.

PMID- 20157609
TI  - The role of regulatory T cells in cancer.
AB  - There has been an explosion of literature focusing on the role of regulatory T
      (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg
      cells play an active and significant role in the progression of cancer, and have
      an important role in suppressing tumor-specific immunity. Thus, there is a clear
      rationale for developing clinical strategies to diminish their regulatory
      influences, with the ultimate goal of augmenting antitimor immunity. Therefore,
      manipulation of Treg cells represent new strategies for cancer treatment. In this
      Review, I will summarize and review the explosive recent studies demonstrating
      that Treg cells are increased in patients with malignancies and restoration of
      antitumor immunity in mice and humans by depletion or reduction of Treg cells. In
      addition, I will discuss both the prognostic value of Treg cells in tumor
      progression in tumor-bearing hosts and the rationale for strategies for
      therapeutic vaccination and immunotherapeutic targeting of Treg cells with drugs
      and microRNA.

PMID- 20157613
TI  - Role of Cordycepin and Adenosine on the Phenotypic Switch of Macrophages via
      Induced Anti-inflammatory Cytokines.
AB  - BACKGROUND: Chronic low grade inflammation is closely linked to type II diabetes,
      obesity, and atherosclerosis. Macrophages play a key role in the regulation of
      pro- or anti-inflammatory actions at the lesion sites of disease. Components of
      cordyceps militaris, cordycepin and adenosine, have been used for the modulation
      of inflammatory diseases. The effects of cordycepin in the modulation of
      macrophages have yet to be elucidated. We investigated the effects of cordycepin
      and adenosine on the morphological changes of macrophages under the inflammatory
      condition of LPS and an anti-inflammatory condition involving high concentrations
      of adenosine. METHODS: We confirmed the mRNA levels of the M1/M2 cytokine genes
      through RT-PCR and morphological change. RESULTS: LPS-activated macrophages
      returned to their inactivated original shape, i.e., they looked like naive
      macrophages, through the treatment with high concentrations of cordycepin (40
      microg/ml). LPS and adenosine activated macrophages also returned to their
      original inactivated shapes after cordycepin treatment; however, at relatively
      higher levels of cordycepin than adenosine. This change did not occur with
      relatively low concentrations of cordycepin. Adenosine down-regulated the gene
      expression of M1 cytokines (IL-1beta, TNF-alpha) and chemokines (CX3CR1, RANTES),
      as well as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-beta) were
      up-regulated by both cordycepin and adenosine. CONCLUSION: Based on these
      observations, both cordycepin and adenosine regulated the phenotypic switch on
      macrophages and suggested that cordycepin and adenosine may potentially be used
      as immunomodulatory agents in the treatment of inflammatory disease.

PMID- 20157615
TI  - Swiprosin-1 Regulates Cytokine Expression of Human Mast Cell Line HMC-1 through
      Actin Remodeling.
AB  - BACKGROUND: Swiprosin-1 was identified in human CD8+ lymphocytes, mature B cells
      and non-lymphonoid tissue. We have recently reported that swiprosin-1 is
      expressed in mast cells and up-regulated in both in vitro and in vivo. METHODS:
      The expression of cytokines and swiprosin-1 were determined by by real time PCR
      and conventional PCR. Pharmacological inhibitors were treated to investigate
      potential mechanism of swiprosin-1 in mast cell activation. Actin content was
      evaluated by confocal microscopy and flow cytometry. RESULTS: The swiprosin-1
      augmented PMA/A23187-induced expression of cytokines and release of histamine.
      However, knock-down of swiprosin-1 showed only a modest effect on PMA/A23187
      induced cytokine expression, suggesting that swiprosin-1 has gain-of-function
      characteristics. Swiprosin-1 was found in microvilli-like membrane protrusions
      and highly co-localized with F-actin. Importantly, either disruption of actin by
      cytochalasin B or inhibition of PI3 kinase, an enzyme involved in actin
      remodeling, by wortmannin blocked cytokine expression only in swiprosin-1
      overexpressing cells. CONCLUSION: These results suggest that swiprosin-1
      modulates mast cell activation potentially through actin regulation.

PMID- 20157614
TI  - Recombinant DNA and Protein Vaccines for Foot-and-mouth Disease Induce Humoral
      and Cellular Immune Responses in Mice.
AB  - BACKGROUND: Foot-and-mouth disease virus (FMDV) is a small single-stranded RNA
      virus which belongs to the family Picornaviridae, genus Apthovirus. It is a
      principal cause of FMD which is highly contagious in livestock. In a wild type
      virus infection, infected animals usually elicit antibodies against structural
      and non-structural protein of FMDV. A structural protein, VP1, is involved in
      neutralization of virus particle, and has both B and T cell epitopes. A RNA
      dependent RNA polymerase, 3D, is highly conserved among other serotypes and
      strongly immunogenic, therefore, we selected VP1 and 3D as vaccine targets.
      METHODS: VP1 and 3D genes were codon-optimized to enhance protein expression
      level and cloned into mammalian expression vector. To produce recombinant
      protein, VP1 and 3D genes were also cloned into pET vector. The VP1 and 3D DNA or
      proteins were co-immunized into 5 weeks old BALB/C mice. RESULTS: Antigen
      specific serum antibody (Ab) responses were detected by Ab ELISA. Cellular immune
      response against VP1 and 3D was confirmed by ELISpot assay. CONCLUSION: The
      results showed that all DNA- and protein-immunized groups induced cellular immune
      responses, suggesting that both DNA and recombinant protein vaccine
      administration efficiently induced Ag-specific humoral and cellular immune
      responses.

PMID- 20157616
TI  - Expression pattern of immunoproteasome subunits in human thymus.
AB  - The expression pattern of immunoproteasomes in human thymus has not been analyzed
      but may have important consequences during thymic selection. Here we examined the
      expression patterns of immunoproteasome subunits in fetal and adult thymic
      tissues by immunohistochemistry and found that all three subunits are expressed
      in both cortical and medullary stromal cells. These data suggest that thymic
      selection in human can be affected by peptide repertoires generated by
      immunoproteasomes.

PMID- 20157617
TI  - Pro-angiogenic effect of IFNgamma is dependent on the PI3K/mTOR/translational
      pathway in human retinal pigmented epithelial cells.
AB  - PURPOSE: To investigate the molecular signaling pathway of Interferon gamma
      (IFNgamma) contributing to angiogenesis in retinal pigmented epithelial (RPE)
      cells and the role of Phosphoinositide 3-kinase (PI3K)/mammalian target of
      rapamycin (mTOR) in this process. METHODS: Human adult and fetal RPE cells were
      used in this study. Real-time polymerase chain reaction was used to detect human
      vascular endothelial growth factor (VEGF) mRNA expression. Thiazolyl blue
      tetrazolium bromide (MTT) assay was used to detect cell viability. VEGF
      expression from cell supernatant was measured using enzyme-linked immunosorbent
      assay (ELISA). Small interfering RNA (SiRNA) of signal transducers and activators
      of transcription 1 (stat1) and protein kinases B (akt) were transfected into ARPE
      19 cells to directly study the roles of these molecules in VEGF expression.
      Sodium dodecyl sulfate PAGE (SDS-PAGE) and western blot analysis were used to
      detect the expression of signaling molecules. RESULTS: IFNgamma promoted human
      VEGF expression in both adult and fetal RPE cells. The PI-3K/Akt/mTOR/p70 S6
      kinase pathway is required for IFNgamma-induced VEGF expression in retinal cells.
      The mTOR inhibitor, rapamycin, along with the SiRNA targeted to akt and the PI3K
      inhibitor, LY294002, decreased hVEGF secretion from RPE cells. Moreover, IFNgamma
      induced hVEGF expression was not affected by SiRNA targeted to Stat1, implying
      that the classic Jak-Stat1 pathway of IFNgamma may not be involved in this
      process. CONCLUSIONS: We provide evidence that IFNgamma induces VEGF expression
      in human retinal pigment epithelial cells. Our work emphasizes that the
      activation of the PI-3K/mTOR/translational pathway is important for IFNgamma
      mediated VEGF expression in RPE cells. By elucidating molecular signaling
      involved in this process, our findings provide further mechanistic insight into
      the successful clinical application of rapamycin therapy for choroidal
      neovascularization in age-related macular degeneration (AMD) and uveitis.

PMID- 20157618
TI  - Complement component 3: an assessment of association with AMD and analysis of
      gene-gene and gene-environment interactions in a Northern Irish cohort.
AB  - PURPOSE: A non-synonymous single nucleotide polymorphism (SNP) in complement
      component 3 has been shown to increase the risk of age-related macular
      degeneration (AMD). We assess its effect on AMD risk in a Northern Irish sample,
      test for gene-gene and gene-environment interaction, and review a risk prediction
      model. METHODS: SNP rs2230199 was genotyped in 1,358 samples, which comprised 437
      cases, 436 no-disease controls, and 485 participants randomly sampled from the
      Northern Ireland population. Allele frequencies were assessed in cases and
      controls. Logistic regression analysis was used to assess interaction and develop
      a risk prediction model. RESULTS: We report a minor allele frequency of 0.248 for
      rs2230199 in the population (n=485), 0.296 in cases (n=437), and 0.221 in
      controls (n=436; odds ratio [OR]=1.48; confidence interval [CI]: 1.19-1.85;
      p=0.0003). The significant association is retained following multivariate
      analysis with adjustment for age, smoking status, Complement Factor H (CFH), Age
      Related Maculopathy Susceptibility 2 (ARMS2), Complement Component 2 (CC2), and
      Complement Factor B (CFB; OR=1.45; CI: 1.10-1.91; p=0.009). No evidence to
      support an interaction between any of the covariates within the regression model
      was found. The area under the receiver operator characteristic curve calculated
      for the fully adjusted model, including all variables, was 0.86 for late AMD.
      CONCLUSIONS: Our study confirmed the association between Complement Component 3
      (C3) and late-stage AMD. There was no evidence for an interaction with
      environmental exposures, nor did we find data to support a gene-gene effect.

PMID- 20157619
TI  - Bestrophin 2 is expressed in human non-pigmented ciliary epithelium but not
      retinal pigment epithelium.
AB  - PURPOSE: Mice in which bestrophin 2 (Best2) is disrupted exhibit changes in
      aqueous flow and drainage, resulting in a reduction in intraocular pressure in
      comparison to wild-type mice. Best2 encodes a putative anion channel localized
      uniquely to the basolateral plasma membrane of non-pigmented epithelium cells in
      mice. In this study, we examine the localization of Best2 in the human eye.
      METHODS: Rabbit polyclonal antibodies recognizing human Best2 (hBest2) were
      generated and characterized for use in western blot, immunoprecipitation, and
      immunofluorescence assays. The expression of hBest2 using these antibodies was
      examined using human donor eye tissues. RESULTS: We could not detect hBest2 in
      human ciliary bodies or other ocular tissues by western blot. However, when
      enriched by immunoprecipitation, hBest2 was identified in ciliary bodies, but not
      in the retinal pigment epithelium. Using immunofluorescence, we located hBest2 in
      the basolateral plasma membrane of non-pigmented epithelial cells. CONCLUSIONS:
      We found expression of hBest2 similar to mice only in NPE cells. These data
      suggest that Best2 may play a functional role in the regulation of aqueous flow
      and drainage in humans. We conclude that Best2 represents a new potential target
      for glaucoma therapy.

PMID- 20157620
TI  - A null mutation in CABP4 causes Leber's congenital amaurosis-like phenotype.
AB  - PURPOSE: To describe the finding of a novel calcium binding protein 4 (CABP4)
      mutation in a family with Leber congenital amaurosis (LCA) phenotype. METHODS:
      Homozygosity mapping was performed in a consanguineous family with four affected
      members originally referred as cases of LCA. Detailed electroretinographic
      recordings were obtained. RESULTS: A novel homozygous single base-pair insertion
      was identified in all four siblings. The patients had an LCA-like phenotype,
      including either flat or greatly diminished electroretinographic activity.
      CONCLUSIONS: This report significantly expands on the phenotype associated with
      calcium binding protein 4 mutations, which has so far been limited to congenital
      stationary night blindness, and further demonstrates how molecular data often
      blur the boundaries between what are believed to be clinically distinct retinal
      disorders.

PMID- 20157621
TI  - Global Validation of Linear Model Assumptions.
AB  - An easy-to-implement global procedure for testing the four assumptions of the
      linear model is proposed. The test can be viewed as a Neyman smooth test and it
      only relies on the standardized residual vector. If the global procedure
      indicates a violation of at least one of the assumptions, the components of the
      global test statistic can be utilized to gain insights into which assumptions
      have been violated. The procedure can also be used in conjunction with associated
      deletion statistics to detect unusual observations. Simulation results are
      presented indicating the sensitivity of the procedure in detecting model
      violations under a variety of situations, and its performance is compared with
      three potential competitors, including a procedure based on the Box-Cox power
      transformation. The procedure is demonstrated by applying it to a new car mileage
      data set and a water salinity data set that has been used previously to
      illustrate model diagnostics.

PMID- 20157623
TI  - Adherence to Scheduled Sessions in a Randomized Field Trial of Case Management:
      The Criminal Justice-Drug Abuse Treatment Studies Transitional Case Management
      Study.
AB  - The Transitional Case Management (TCM) study, one of the projects of the Criminal
      Justice Drug Abuse Treatment Studies (CJ-DATS) cooperative, was a multi-site
      randomized test of whether a strengths-based case management intervention
      provided during an inmate's transition from incarceration to the community
      increases participation in community substance abuse treatment, enhances access
      to needed social services, and improves drug use and crime outcomes. As in many
      intervention studies, TCM experienced a relatively large percentage of treatment
      group participants who attended few or no scheduled sessions. The paper discusses
      issues with regard to participation in community case management sessions,
      examines patterns of session attendance among TCM participants, and analyzes
      client and case manager characteristics that are associated with number of
      sessions attended and with patterns of attendance. The average number of sessions
      (out of 12) attended was 5.7. Few client or case manager characteristics were
      found to be significantly related to session attendance. Clinical and research
      implications of the findings and of adherence in case management generally are
      discussed.

PMID- 20157622
TI  - Meiotic Recombination in Schizosaccharomyces pombe: A Paradigm for Genetic and
      Molecular Analysis.
AB  - The fission yeast Schizosaccharomyces pombe is especially well-suited for both
      genetic and biochemical analysis of meiotic recombination. Recent studies have
      revealed ~50 gene products and two DNA intermediates central to recombination,
      which we place into a pathway from parental to recombinant DNA. We divide
      recombination into three stages - chromosome alignment accompanying nuclear
      "horsetail" movement, formation of DNA breaks, and repair of those breaks - and
      we discuss the roles of the identified gene products and DNA intermediates in
      these stages. Although some aspects of recombination are similar to those in the
      distantly related budding yeast Saccharomyces cerevisiae, other aspects are
      distinctly different. In particular, many proteins required for recombination in
      one species have no clear ortholog in the other, and the roles of identified
      orthologs in regulating recombination often differ. Furthermore, in S. pombe the
      dominant joint DNA molecule intermediates contain single Holliday junctions, and
      intersister joint molecules are more frequent than interhomolog types, whereas in
      S. cerevisiae interhomolog double Holliday junctions predominate. We speculate
      that meiotic recombination in other organisms shares features of each of these
      yeasts.

PMID- 20157624
TI  - Disruption of biological rhythms as a core problem and therapeutic target in mood
      disorders: the emerging concept of 'rhythm regulators'.
AB  - Biological rhythms have always been considered to be disrupted in depression,
      with the predominant theory being that of hyperarousal. However, recent data
      suggest that it might be more appropriate to suggest that depressed patients are
      incapable of achieving and maintaining the particular level of internal
      homeostasis which permits them to function smoothly, to lower the level of
      arousal during sleep sufficiently so that quality of sleep is good, and to
      increase this level enough during the day so the person can function properly.
      Therefore, the transition from one state to another is somewhat problematic,
      delayed, incomplete and desynchronised. Thus, agents with a 'rhythm stabilising'
      effect could be beneficial in the treatment of mood disorders. Such an agent
      should have a beneficial effect on restoring and stabilising the rhythm of a
      physiological function while not pushing it towards a specific pole, or inducing
      the opposite pole; it should also allow response to internal and environmental
      stimuli and zeitgebers, and restore synchronisation of the various body rhythms
      while not inducing or worsening desynchronisation. Agomelatine could represent
      the first of a new class of 'rhythm stabilising antidepressants', but further
      research is necessary to support this theory.

PMID- 20157625
TI  - Novel Models of Intertemporal Valuation: Past and Future Outcomes.
AB  - Temporal discounting refers to the reduction in the present subjective value of
      an outcome as a function of the temporal distance to that outcome. Though a
      number of mathematical models have been proposed to describe this time/value
      relationship, this search has largely excluded insights from the literature on
      memory decay. This study examines the utility of memory decay models by comparing
      the fits of four of these models to fits from established temporal discounting
      models using past and future temporal discounting data. These results (1) suggest
      that a single model describes valuation of both future and past outcomes, (2)
      indicate the exponential-power model, from memory decay literature, is
      statistically superior in fitting discounting data from both past and future
      outcomes, and (3) support the advancing perspective of the psychological
      interconnectedness of the future and past.

PMID- 20157626
TI  - MULTIVARIATE ANALYSIS AND JACOBI ENSEMBLES: LARGEST EIGENVALUE, TRACY-WIDOM
      LIMITS AND RATES OF CONVERGENCE.
AB  - Let A and B be independent, central Wishart matrices in p variables with common
      covariance and having m and n degrees of freedom, respectively. The distribution
      of the largest eigenvalue of (A + B)(-1)B has numerous applications in
      multivariate statistics, but is difficult to calculate exactly. Suppose that m
      and n grow in proportion to p. We show that after centering and, scaling, the
      distribution is approximated to second-order, O(p(-2/3)), by the Tracy-Widom law.
      The results are obtained for both complex and then real-valued data by using
      methods of random matrix theory to study the largest eigenvalue of the Jacobi
      unitary and orthogonal ensembles. Asymptotic approximations of Jacobi polynomials
      near the largest zero play a central role.

PMID- 20157628
TI  - Free and glycosylated sterol bioaccumulation in developing Cycas micronesica
      seeds.
AB  - The bioaccumulation of free and glycosylated forms of stigmasterol and beta
      sitosterol were determined from Cycas micronesica K.D. Hill seeds throughout seed
      ontogeny. Per-seed pool of the four compounds increased linearly from 2 to 24
      months, indicating no developmental period elicited a major shift in the rate of
      bioaccumulation. The slopes were not homogeneous, signifying a change in relative
      sterol profile concomitant with seed maturation. This shift was in favour of the
      glucosides, as their rate of accumulation exceeded that of the free sterols.
      Stigmasterol content exceeded that of beta-sitosterol, but ontogeny did not
      influence the ratio of these dominant sterols. The quantity and quality of sterol
      exposure during consumption of foods prepared from gametophytes by humans is
      strongly influenced by age of harvested seeds. Results are critical for a further
      understanding of the link between human neurodegenerative diseases and historical
      consumption of foods derived from the seed gametophyte tissue.

PMID- 20157627
TI  - Differential Plasma Glycoproteome of p19 Skin Cancer Mouse Model Using the Corra
      Label-Free LC-MS Proteomics Platform.
AB  - A proof-of-concept demonstration of the use of label-free quantitative
      glycoproteomics for biomarker discovery workflow is presented here, using a mouse
      model for skin cancer as an example. Blood plasma was collected from 10 control
      mice, and 10 mice having a mutation in the p19(ARF) gene, conferring them high
      propensity to develop skin cancer after carcinogen exposure. We enriched for N
      glycosylated plasma proteins, ultimately generating deglycosylated forms of the
      modified tryptic peptides for liquid chromatography mass spectrometry (LC-MS)
      analyses. LC-MS runs for each sample were then performed with a view to
      identifying proteins that were differentially abundant between the two mouse
      populations. We then used a recently developed computational framework, Corra, to
      perform peak picking and alignment, and to compute the statistical significance
      of any observed changes in individual peptide abundances. Once determined, the
      most discriminating peptide features were then fragmented and identified by
      tandem mass spectrometry with the use of inclusion lists. We next assessed the
      identified proteins to see if there were sets of proteins indicative of specific
      biological processes that correlate with the presence of disease, and
      specifically cancer, according to their functional annotations. As expected for
      such sick animals, many of the proteins identified were related to host immune
      response. However, a significant number of proteins also directly associated with
      processes linked to cancer development, including proteins related to the cell
      cycle, localisation, trasport, and cell death. Additional analysis of the same
      samples in profiling mode, and in triplicate, confirmed that replicate MS
      analysis of the same plasma sample generated less variation than that observed
      between plasma samples from different individuals, demonstrating that the
      reproducibility of the LC-MS platform was sufficient for this application. These
      results thus show that an LC-MS-based workflow can be a useful tool for the
      generation of candidate proteins of interest as part of a disease biomarker
      discovery effort.

PMID- 20157629
TI  - Distribution of free and glycosylated sterols within Cycas micronesica plants.
AB  - Flour derived from Cycas micronesica seeds was once the dominant source of starch
      for Guam's residents. Cycad consumption has been linked to high incidence of
      human neurodegenerative diseases. We determined the distribution of the sterols
      stigmasterol and beta-sitosterol and their derived glucosides stigmasterol beta-d
      glucoside and beta-sitosterol beta-d-glucoside among various plant parts because
      they have been identified in cycad flour and have been shown to elicit
      neurodegenerative outcomes. All four compounds were common in seeds, sporophylls,
      pollen, leaves, stems, and roots. Roots contained the greatest concentration of
      both free sterols, and photosynthetic leaflet tissue contained the greatest
      concentration of both steryl glucosides. Concentration within the three stem
      tissue categories was low compared to other organs. Reproductive sporophyll
      tissue contained free sterols similar to seeds, but greater concentration of
      steryl glucosides than seeds. One of the glucosides was absent from pollen.
      Concentration in young seeds was higher than old seeds as reported earlier, but
      concentration did not differ among age categories of leaf, sporophyll, or
      vascular tissue. The profile differences among the various tissues within these
      organs may help clarify the physiological role of these compounds.

PMID- 20157630
TI  - The ABCs of Math: A Genetic Analysis of Mathematics and Its Links With Reading
      Ability and General Cognitive Ability.
AB  - The goal of this first major report from the Western Reserve Reading Project Math
      component is to explore the etiology of the relationship among tester
      administered measures of mathematics ability, reading ability, and general
      cognitive ability. Data are available on 314 pairs of monozygotic and same-sex
      dizygotic twins analyzed across 5 waves of assessment. Univariate analyses
      provide a range of estimates of genetic (h(2) = .00 -.63) and shared (c(2) = .15
      .52) environmental influences across math calculation, fluency, and problem
      solving measures. Multivariate analyses indicate genetic overlap between math
      problem solving with general cognitive ability and reading decoding, whereas math
      fluency shares significant genetic overlap with reading fluency and general
      cognitive ability. Further, math fluency has unique genetic influences. In
      general, math ability has shared environmental overlap with general cognitive
      ability and decoding. These results indicate that aspects of math that include
      problem solving have different genetic and environmental influences than math
      calculation. Moreover, math fluency, a timed measure of calculation, is the only
      measured math ability with unique genetic influences.

PMID- 20157631
TI  - The Community Pulling Together: A  Tribal Community-University Partnership 
      Project to Reduce Substance Abuse and  Promote Good Health in a Reservation 
      Tribal Community.
AB  - Alcohol and drug abuse are major areas of concern for many American Indian=Alaska
      Native communities. Research on these problems has often been less than
      successful, in part because many researchers are not sensitive to the culture and
      traditions of the tribes and communities with which they are working. They
      alsooften fail to incorporate tribal customs, traditions, and values into the
      interventions developed to deal with substance abuse. The authors describe the
      use of community-based participatory research and tribal participatory research
      approaches to develop a culturally sensitive substance abuse prevention program
      for Native youth. This project, The Community Pulling Together: Healing of the
      Canoe, is a collaboration between the Suquamish Tribe and the Alcohol and Drug
      Abuse Institute at the University of Washington, Seattle, Washington.

PMID- 20157632
TI  - Comparison of Isotonic Designs for Dose-Finding.
AB  - We compare several decision rules for allocating subjects to dosages that are
      based on sequential isotonic estimates of a monotone dose-toxicity curve. We
      conclude that the decision rule in which the next assignment is to the dose
      having probability of toxicity closest to target does not work well. The best
      rule in our comparison is given by the cumulative cohort design. According to
      this design, the dose for the next subject is decreased, increased, or repeated
      depending on the distance between the estimated toxicity rate at the current dose
      and the target quantile.

PMID- 20157633
TI  - Detectors for single-molecule fluorescence imaging and spectroscopy.
AB  - Single-molecule observation, characterization and manipulation techniques have
      recently come to the forefront of several research domains spanning chemistry,
      biology and physics. Due to the exquisite sensitivity, specificity, and unmasking
      of ensemble averaging, single-molecule fluorescence imaging and spectroscopy have
      become, in a short period of time, important tools in cell biology, biochemistry
      and biophysics. These methods led to new ways of thinking about biological
      processes such as viral infection, receptor diffusion and oligomerization,
      cellular signaling, protein-protein or protein-nucleic acid interactions, and
      molecular machines. Such achievements require a combination of several factors to
      be met, among which detector sensitivity and bandwidth are crucial. We examine
      here the needed performance of photodetectors used in these types of experiments,
      the current state of the art for different categories of detectors, and actual
      and future developments of single-photon counting detectors for single-molecule
      imaging and spectroscopy.

PMID- 20157634
TI  - Resolving Conformational and Rotameric Exchange in Spin-Labeled Proteins Using
      Saturation Recovery EPR.
AB  - The function of many proteins involves equilibria between conformational
      substates, and to elucidate mechanisms of function it is essential to have
      experimental tools to detect the presence of conformational substates and to
      determine the time scale of exchange between them. Site-directed spin labeling
      (SDSL) has the potential to serve this purpose. In proteins containing a
      nitroxide side chain (R1), multicomponent electron paramagnetic resonance (EPR)
      spectra can arise either from equilibria involving different conformational
      substates or rotamers of R1. To employ SDSL to uniquely identify conformational
      equilibria, it is thus essential to distinguish between these origins of
      multicomponent spectra. Here we show that this is possible based on the time
      scale for exchange of the nitroxide between distinct environments that give rise
      to multicomponent EPR spectra; rotamer exchange for R1 lies in the ~0.1-1 MUs
      range, while conformational exchange is at least an order of magnitude slower.
      The time scales of exchange events are determined by saturation recovery EPR, and
      in favorable cases, the exchange rate constants between substates with lifetimes
      of approximately 1-70 MUs can be estimated by the approach.

PMID- 20157635
TI  - Migraine in affectively ill Mexican adolescents.
AB  - The objective of this cross-sectional study was to determine the prevalence of
      migraine headache among depressed Latino adolescents of Mexican American origin.
      This is, to the best of our knowledge, the first study of the prevalence of
      migraine among depressed adolescents of any ethnic/racial background. In a mental
      health clinic for the indigent, 132 consecutive Latino adolescents fulfilling the
      DSM-IV criteria for major depressive episode were compared with a sample of
      adolescents with other mental disorders. Logistic regression was used to test for
      associations and control for confounding effects. The prevalence of migraine
      headache among depressed adolescents was 6 times greater than that of the
      comparison patients (OR = 5.98, z = 2.35, p = 0.019). This finding is consistent
      with previously published reports involving adult samples, in which the
      prevalence of migraine was found to exceed that in the general population.
      However, contrary to what we previously found in Latino adults, the prevalence of
      migraine was not higher in bipolar than in unipolar adolescents.

PMID- 20157636
TI  - Dentinogenesis and Dentin Sialophosphoprotein (DSPP).
AB  - Dentin sialophosphoprotein (DSPP) is critical for proper mineralization of tooth
      dentin, and understanding its structure and function should yield important
      insights into how dentin biomineralization is controlled. During the recent six
      years, I have focused on characterizing DSPP-derived proteins isolated from
      developing porcine teeth. Porcine DSPP is expressed and secreted by odontoblasts
      and is processed by BMP-1, MMP-20 and MMP-2 into three main parts: dentin
      sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein (DPP).
      We have learned that DSP is a proteoglycan that forms covalent dimers, DGP is a
      phosphorylated glycoprotein, and DPP is a highly phosphorylated intrinsically
      disordered protein that shows extensive length polymorphisms due to the genetic
      heterogeneity of its coding region.

PMID- 20157637
TI  - Current Directions in Mediation Analysis.
AB  - Mediating variables continue to play an important role in psychological theory
      and research. A mediating variable transmits the effect of an antecedent variable
      on to a dependent variable, thereby providing more detailed understanding of
      relations among variables. Methods to assess mediation have been an active area
      of research for the last two decades. This paper describes the current state of
      methods to investigate mediating variables.

PMID- 20157639
TI  - Investigation of Mediational Processes Using Parallel Process Latent Growth Curve
      Modeling.
AB  - This study investigated a method to evaluate mediational processes using latent
      growth curve modeling. The mediator and the outcome measured across multiple time
      points were viewed as 2 separate parallel processes. The mediational process was
      defined as the independent variable influencing the growth of the mediator,
      which, in turn, affected the growth of the outcome. To illustrate modeling
      procedures, empirical data from a longitudinal drug prevention program,
      Adolescents Training and Learning to Avoid Steroids, were used. The program
      effects on the growth of the mediator and the growth of the outcome were examined
      first in a 2-group structural equation model. The mediational process was then
      modeled and tested in a parallel process latent growth curve model by relating
      the prevention program condition, the growth rate factor of the mediator, and the
      growth rate factor of the outcome.

PMID- 20157638
TI  - Atherosclerosis: A Link Between Lipid Intake and Protein Tyrosine Nitration.
AB  - Atherosclerosis, a disease characterized by plaque formation in the arterial wall
      that can lead to heart attack and stroke, is a principal cause of death in the
      world. Since the 1990's, protein nitrotyrosine formation has been known to occur
      in the atherosclerotic plaque. This potentially damaging reaction occurs as a
      result of tyrosine modification by reactive nitrogen species, such as nitrogen
      dioxide radical, which forms upon peroxynitrite decomposition or nitrite
      oxidation by hydrogen peroxide-activated peroxidase enzymes. The presence of
      protein-bound nitrotyrosine can be considered an indicator of a loss in the
      natural balance of oxidants and antioxidants, and as such, there is an emerging
      view that protein-bound nitrotyrosine may be a risk factor for cardiovascular
      disease. This review brings together evidence that the accumulation of protein
      nitrotyrosine during atherogenesis is more widespread than initially thought (as
      its presence can be detected not only in the lesion but also in the blood stream
      and other organs) and is closely linked to lipid intake.

PMID- 20157640
TI  - Data Compression Concepts and Algorithms and their Applications to
      Bioinformatics.
AB  - Data compression at its base is concerned with how information is organized in
      data. Understanding this organization can lead to efficient ways of representing
      the information and hence data compression. In this paper we review the ways in
      which ideas and approaches fundamental to the theory and practice of data
      compression have been used in the area of bioinformatics. We look at how basic
      theoretical ideas from data compression, such as the notions of entropy, mutual
      information, and complexity have been used for analyzing biological sequences in
      order to discover hidden patterns, infer phylogenetic relationships between
      organisms and study viral populations. Finally, we look at how inferred grammars
      for biological sequences have been used to uncover structure in biological
      sequences.

PMID- 20157641
TI  - A Simulation Study of Mediated Effect Measures.
AB  - Analytical solutions for point and variance estimators of the mediated effect,
      the ratio of the mediated to the direct effect, and the proportion of the total
      effect that is mediated were studied with statistical simulations. We compared
      several approximate solutions based on the multivariate delta method and second
      order Taylor series expansions to the empirical standard deviation of each
      estimator and theoretical standard error when available. The simulations
      consisted of 500 replications of three normally distributed variables for eight
      sample sizes (N = 10, 25, 50, 100, 500, 1000, and 5000) and 64 parameter value
      combinations. The different solutions for the standard error of the indirect
      effect were very similar for sample sizes of at least 50, except when the
      independent variable was dichotomized. A sample size of at least 500 was needed
      for accurate point and variance estimates of the proportion mediated. The point
      and variance estimates of the ratio of the mediated to nonmediated effect did not
      stabilize until the sample size was 2,000 for the all continuous variable case.
      Implications for the estimation of mediated effects in experimental and
      nonexperimental studies are discussed.

PMID- 20157642
TI  - Confidence Limits for the Indirect Effect: Distribution of the Product and
      Resampling Methods.
AB  - The most commonly used method to test an indirect effect is to divide the
      estimate of the indirect effect by its standard error and compare the resulting z
      statistic with a critical value from the standard normal distribution. Confidence
      limits for the indirect effect are also typically based on critical values from
      the standard normal distribution. This article uses a simulation study to
      demonstrate that confidence limits are imbalanced because the distribution of the
      indirect effect is normal only in special cases. Two alternatives for improving
      the performance of confidence limits for the indirect effect are evaluated: (a) a
      method based on the distribution of the product of two normal random variables,
      and (b) resampling methods. In Study 1, confidence limits based on the
      distribution of the product are more accurate than methods based on an assumed
      normal distribution but confidence limits are still imbalanced. Study 2
      demonstrates that more accurate confidence limits are obtained using resampling
      methods, with the bias-corrected bootstrap the best method overall.

PMID- 20157643
TI  - EPR and ENDOR Investigation of Rhodosemiquinone in Bacterial Reaction Centers
      Formed by B-Branch Electron Transfer.
AB  - In photosynthetic bacteria, light-induced electron transfer takes place in a
      protein called the reaction center (RC) leading to the reduction of a bound
      ubiquinone molecule, Q(B), coupled with proton binding from solution. We used
      electron paramagnetic resonance (EPR) and electron-nuclear double resonance
      (ENDOR) to study the magnetic properties of the protonated semiquinone, an
      intermediate proposed to play a role in proton coupled electron transfer to Q(B).
      To stabilize the protonated semiquinone state, we used a ubiquinone derivative,
      rhodoquinone, which as a semiquinone is more easily protonated than
      ubisemiquinone. To reduce this low-potential quinone we used mutant RCs modified
      to directly reduce the quinone in the Q(B) site via B-branch electron transfer
      (Paddock et al. in Biochemistry 44:6920-6928, 2005). EPR and ENDOR signals were
      observed upon illumination of mutant RCs in the presence of rhodoquinone. The EPR
      signals had g values characteristic of rhodosemiquinone (g(x) = 2.0057, g(y) =
      2.0048, g(z) ~ 2.0018) at pH 9.5 and were changed at pH 4.5. The ENDOR spectrum
      showed couplings due to solvent exchangeable protons typical of hydrogen bonds
      similar to, but different from, those found for ubisemiquinone. This approach
      should be useful in future magnetic resonance studies of the protonated
      semiquinone.

PMID- 20157644
TI  - Atorvastatin therapy is associated with greater and faster cerebral hemodynamic
      response.
AB  - Hypercholesterolemia in midlife increases the risk of subsequent cognitive
      decline, neurovascular disease, and Alzheimer's disease (AD), and statin use is
      associated with reduced prevalence of these outcomes. While statins improve
      vasoreactivity in peripheral arteries and large cerebral arteries, little is
      known about the effects of statins on cerebral hemodynamic responses and
      cognition in healthy asymptomatic adults. At the final visit of a 4-month
      randomized, controlled, double-blind study comparing atorvastatin 40 mg daily to
      placebo, 16 asymptomatic middle-aged adults (15 had useable data) underwent blood
      oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI),
      arterial spin labeling (ASL) quantitative cerebral blood flow (qCBF), dynamic
      susceptibility contrast (DSC) and structural imagings of the brain. Using a
      memory recognition task requiring discrimination of previously viewed (PV) and
      novel (NV) human faces, fMRI was used to elicit activation from brain regions
      known to be vulnerable to changes associated with AD. The BOLD signal amplitude
      (PV > NV) and latency to each stimulus were tested on a voxel basis between the
      atorvastatin (n=8) and placebo (n=7) groups. Persons randomized to atorvastatin
      not only showed significantly greater BOLD amplitude in the right angular gyrus,
      left superior parietal lobule, right middle temporal and superior sulcus than the
      placebo group, but also decreased hemodynamic response latencies in the right
      middle frontal gyrus, left precentral gyrus, left cuneus and right posterior
      middle frontal gyrus. However, neither the resting cerebral blood flow (CBF)
      measured with ASL nor the mean transit time (MTT) of cerebral perfusion
      calculated from DSC showed differences in these regions in either group. The drug
      related BOLD differences during memory recognition suggest that atorvastatin may
      have improved cerebral small vessel vasoreactivity, possibly through an effect on
      endothelial function. Furthermore, these results suggest that the effect of
      atorvastatin on the task-induced BOLD signal may not be a simple consequence of
      baseline flow change.

PMID- 20157645
TI  - Case report of recurrent acute appendicitis in a residual tip.
AB  - INTRODUCTION: Residual appendicitis involving the stump of the appendix has been
      well described in the literature in the past. CASE REPORT: We report the case of
      a 43 year old male with acute onset of abdominal pain who had undergone an
      appendicectomy ten years previously. Ultrasound revealed the presence of an
      inflamed tubular structure. Subsequent laparotomy and histology confirmed that
      this structure was an inflamed residual appendiceal tip. CONCLUSION: Residual tip
      appendicitis has not been reported in the literature previously and should be
      considered in the differential diagnosis of localised peritonitis in a patient
      with a history of a previous open appendicectomy.

PMID- 20157646
TI  - Cardiac tamponade and successful pericardiocentesis in an extremely low birth
      weight neonate with percutaneously inserted central venous line: a case report.
AB  - BACKGROUND: Pericardial effusion and cardiac tamponade are rare but life
      threatening complications of percutaneosuly inserted central line (PICL) use in
      extremely low birth weight (ELBW) neonates, with an incidence reported between
      0.07% and 2% of PICLs placement. Timely diagnosis and pericardiocentesis has been
      proven to be life-saving. CASE PRESENTATION: The patient was a 620 g birth weight
      neonate who presented with sudden cardiac instability 18 days after the insertion
      of a PICL and in spite of a presumed satisfactory position of the catheter tip.
      The transthoracic echocardiography demonstrated severe pericardial effusion with
      evidence of cardiac tamponade. Successful urgent subxiphoid pericardiocentesis
      was performed; totally 2 ml of whitish fluid was collected, which resulted
      consistent to the composition of the hyperosmolar TPN solution infused.
      CONCLUSION: Cardiac tamponade should be considered in any newborn with a
      peripherally inserted central catheter who presents with cardiorespiratory
      instability (bradycardia, cyanosis and metabolic acidosis), even when lines are
      believed to be placed correctly.

PMID- 20157647
TI  - Effect of aging conditions on the repair bond strength of a microhybrid and a
      nanohybrid resin composite.
AB  - PURPOSE: this study evaluated the effect of different aging methods on the repair
      bond strength and failure types of a microhybrid and a nanohybrid composite.
      MATERIALS AND METHODS: disk-shaped microhybrid (Quadrant Anterior Shine-QA) and
      nanohybrid (Tetric EvoCeram-TE) resin composite specimens (N = 192, n = 12/per
      group) were photopolymerized and randomly assigned to one of the three aging
      conditions: (1) immersion in deionized water (37 degrees C, 2 months), (2)
      thermocycling (5000 times, 5 to 55  degrees C), (3) immersion in citric acid (pH:
      3.0; 1 week). The control group was stored dry for 24 h at 37 degrees C. After
      aging procedures, the specimens were silica coated (30 microm SiO2) (CoJet-Sand)
      using an intraoral air abrasion device, silanized (ESPESil) and an intermediate
      adhesive resin was applied (Visio-Bond, 3M ESPE). Resin composites, once of the
      same kind as the substrate (QA-QA, TE-TE) and once other than the substrate
      material (QA-TE, TE-QA) were adhered onto the conditioned substrates. Shear force
      was applied to the adhesive interface in a universal testing machine (cross-head
      speed: 1 mm/min). RESULTS: a significant influence of the aging method was
      observed (p < 0.05) but the composite type did not affect the repair bond
      strength (p = 0.755) (2-way ANOVA, Tukey's test). Interaction terms were
      significant (p < 0.05). Thermocycling showed lower results (10 +/- 2.6 to 14.4 +/
      4.4 MPa) than those of other aging methods (12.7 +/- 5.2 to 28 +/- 5.3 MPa).
      Using the substrate and the adherend interchangeably (QA-TE, TE-QA) did not show
      significant differences in the control group, but the results were significant
      after aging (p = 0.007) (2-way ANOVA, Tukey's test). Interaction terms were not
      significant (p = 0.124). The incidence of score A (cohesive failures in the
      substrate) was not significant between the composite combinations in the control
      groups (exclusively 100%) and water-storage aged groups (92% to 100%) (p > 0.05)
      (chi-square). Citric acid aging yielded significantly less incidence of score A
      (8-75%) compared to the control group in all composite combinations (p < 0.05).
      CONCLUSION: both microhybrid and nanohybrid composites could be used either as a
      substrate or as relayering composites in early repairs. Aging factors may
      diminish the repair quality.

PMID- 20157648
TI  - Measuring bond strength between fiber post and root dentin: a comparison of
      different tests.
AB  - PURPOSE: the aim of this study was to evaluate the ability of bond strength tests
      to accurately measure the bond strength of fiber posts luted into root canals.
      MATERIALS AND METHODS: the test methods studied were hourglass microtensile (HM),
      push-out (PS), modified pushout (MP), and pull-out (PL). The evaluated parameters
      were: bond strength values, reliability (using Weibull analysis), failure mode
      (using confocal microscopy), and stress distribution (using finite element
      analysis). Forty human intact single-rooted and endodontically treated teeth were
      divided into four groups. Each group was assigned one of the test methods. The
      samples in the HM and PS groups were 1.0 +/- 0.1 mm thick; the HM samples were
      hourglass shaped and the PS samples were disk shaped. For the PL and MP groups,
      each 1-mm dentin slice was luted with a fiber post piece. Three-dimensional
      models of each group were made and stress was analyzed based on Von Mises
      criteria. RESULTS: PL provided the highest values of bond strength, followed by
      MP, both of which also had greater amounts of adhesive failures. PS showed the
      highest frequency of cohesive failures. MP showed a more homogeneous stress
      distribution and a higher Weibull modulus. CONCLUSION: the specimen design
      directly influences the biomechanical behavior of bond strength tests.

PMID- 20157649
TI  - Micro-raman assessment of the ratio of carbon-carbon double bonds of two adhesive
      systems cured with LED or halogen light-curing units.
AB  - PURPOSE: the purpose of the study was to compare the ratio of carbon-carbon
      double bonds (RDB) of two adhesive systems cured by five different light-curing
      units (LCUs) using micro-Raman spectroscopy. materials and methods: ten samples
      of an etch-and-rinse (Excite), a two-step self-etching adhesive system (AdheSE) -
      ie, primer and bond mixed - and AdheSE Bond only were prepared and cured with one
      of the following LEDs: Elipar Freelight2; Bluephase; SmartLite; Coltolux, each
      for 10 s; or a conventional halogen Prismetics Lite for 10 s or 20 s. Micro-Raman
      spectra were obtained from uncured and cured samples of all three groups to
      calculate the RDB. Data were statistically analyzed using ANOVA. RESULTS: the
      mean RDB values were 62% to 76% (Excite), 36% to 50% (AdheSE Primer+Bond) and 58%
      to 63% (AdheSE Bond). At 20 s, Prismetics Lite produced significantly higher RDB
      in Excite than the other LCUs and Prismetics Lite at 10 s (p < 0.05). Prismetics
      Lite at 20 s and Elipar produced comparable RDB values of AdheSE Bond and AdheSE
      Primer+Bond (p > 0.05). Excite showed significantly higher RDB values than AdheSE
      (p < 0.05) whilst AdheSE Bond showed significantly higher RDB than AdheSE
      Primer+Bond (p < 0.05). CONCLUSION: the etch-and-rinse adhesive cured with the
      halogen LCU for 20 s gave higher conversion than LED LCUs or halogen for 10 s
      curing time. The highest intensity LED [Elipar] produced higher or comparable
      conversion compared to the lower intensity LED LCUs for the same curing time. The
      etch-and-rinse adhesive showed higher RDB than the self-etching adhesive system.
      The presence of the primer in the self-etching adhesive compromised
      polymerisation.

PMID- 20157650
TI  - Reducing the incompatibility between two-step adhesives and resin composite
      luting cements.
AB  - PURPOSE: To determine whether the adverse interaction between a two-step/acidic
      etch-and-rinse adhesive (One-Step Plus [OS], Bisco) and chemically cured resin
      luting cement [Variolink II, Ivoclar Vivadent] can improve adhesive coupling by
      reducing the dentin permeability with an oxalate desensitizer (BisBlock, Bisco).
      MATERIALS AND METHODS: After exposing dentin on the occlusal surfaces of human
      third molars, bonding was performed on either oxalate treated (BB) or nontreated
      (NB) demineralized dentin. A resin luting cement was placed in the format of a
      crown following the light-curing mode (only with the base syringe [LC]) or the
      chemically curing mode (mixture of base and catalyst syringes [CC]). The
      activation of the LC or CC cements was either immediately [IM], meaning soon
      after the placement of LC and the initial set of CC cement (5 min), or after a
      delay of 20 min [DP] for both modes of polymerization. Five teeth were assigned
      to each experimental condition. Teeth were sectioned to obtain sticks with a
      cross-sectional area of 0.95 mm2, which were tested using the microtensile bond
      strength test soon after the specified periods of polymerization. The bond
      strength values of each adhesive were analyzed by three-way repeated measures
      ANOVA and Tukey's tests (alpha = 0.05). Fractographic analysis of the specimens
      was performed using SEM. RESULTS: The delayed polymerization (for both LC and CC
      cements) produced low bond strength values compared to IM activation. When the BB
      was employed, the bond strength values of the CC cement was approximately
      doubled, while the BB did not affect the bond strength of the LC cement. Bond
      strength values of LC cements were higher than CC. The use of BB significantly
      improved the bond strength of CC cement only. The morphological observations
      confirmed the bond strength results. A myriad of voids could be detected in the
      luting cement side when BB was not applied, except for the immediately light
      cured group. CONCLUSION: The use of an oxalate desensitizer (BisBlock) reduced
      the incompatibility between a two-step etch-and rinse adhesive and chemically
      cured resin cements and light-cured systems in the delayed polymerization mode.

PMID- 20157651
TI  - Influence of experimental provisional cements containing zeolite, bone
      hydroxyapatite and linoleic Acid on bond strength of composite to dentin in
      vitro.
AB  - PURPOSE: to evaluate the dentin bond strength of a composite resin material after
      the removal of two experimental cements containing zeolite, bone hydroxyapatite
      and linoleic acid, and one conventional glass-ionomer cement intended as
      provisional cements. MATERIALS AND METHODS: forty extracted caries-free, erupted
      permanent third molars were used. Experimental provisional cements containing
      zeolite and bone hydroxyapatite (BHA) and one conventional glass-ionomer cement
      (GIC) were placed on the dentin surfaces and covered with tinfoil. Cement-covered
      dentin surfaces were stored in distilled water at 37 degrees C +/- 2 degrees C
      for seven days. After this period, temporary cements were mechanically removed,
      dentin surfaces were rinsed in distilled water and dried with an air syringe
      before adhesive application. Dentin bonding agent was applied according to the
      manufacturer's instructions and the adhesion test was performed according to ISO
      TR 11405. RESULTS: the following shear bond strengths for the composite material
      were obtained: no treatment applied (control, group 4): 17.30 +/- 1.37 MPa;
      provisional cement containing BHA (group 2): 15.03 +/- 3.44 MPa; GIC (group 3):
      14.13 +/- 2.85 MPa; provisional cement containing zeolite (group 1): 11.29 +/-
      2.71 MPa. The difference between groups 1 and 4 the control group was
      significant, where as the statistical analysis showed no significant difference
      between the control and BHA groups (ANOVA, Tukey's, p > 0.05). CONCLUSION: in
      clinical applications where the previous application of provisional cements is
      necessary, material choice may influence the bond strength of the subsequent
      composite resin restoration.

PMID- 20157652
TI  - Retention of prefabricated titanium dowels cemented with three luting resins.
AB  - PURPOSE: to evaluate the effects of three luting resins and roughening of the
      dentinal walls on the long-term retention of tapered titanium dowels. MATERIALS
      AND METHODS: ninety-six single-rooted teeth were endodontically treated. All root
      specimens were divided into three groups (n = 32). Dowel spaces were then
      prepared with ISO 90 drills 10 mm deep. Corresponding prefabricated tapered
      titanium dowels were air abraded and luted with Panavia 21 (P21), Super Bond C&B
      (SB) or with Chemiace II (CH) according to the manufacturers' instructions. In
      the subgroups of each luting agent, the dentinal walls were either left in their
      original state as prepared by the drills (n = 16), or roughened with a handheld
      diamondcoated ISO 90 cutting instrument (n = 16). The bonded specimens were
      stored in water at 37 degrees C for 3 days (n = 8) or 150 days with simulated
      aging conditions of 37,500 thermal cycles (5 degrees C/55 degrees C) and 300,000
      mechanical loading cycles with 30 N (n = 8). Dowel retention in N was measured
      using a universal testing machine with a crosshead speed of 2 mm/min. Statistical
      analysis was performed with ANOVAs followed by Scheffe post-hoc tests. RESULTS:
      the dowel retention with P21 and SB was significantly higher than that of CH (p
      <= 0.05). Roughening the dentinal walls significantly increased the retention for
      all cements (p <= 0.01). Storage for 150 days with thermal cycling and mechanical
      loading caused a significant decrease in dowel retention (p <= 0.05). CONCLUSION:
      P21 and SB luting resins provided a durable retention of prefabricated titanium
      dowels in root canals, especially for root canals with roughened dentinal walls,
      as the combined result of sliding friction, micromechanical interlocking and
      adhesive dentin bonding.

PMID- 20157653
TI  - In vitro study of the influence of dentin desensitizing and sealing on the shear
      bond strength of two universal resin cements.
AB  - PURPOSE: To test whether or not dentin desensitizing or sealing methods influence
      the bond strength of universal resin cements. MATERIALS AND METHODS: The bond
      strength of two universal resin cements (RelyXUnicem, Self-adhesive Prototype
      Cement) to human dentin was assessed after different dentin surface treatments
      (test). A conventional resin cement (Panavia 21) served as control. The influence
      of the following pretreatment methods was tested and compared to freshly ground
      dentin: dentin desensitizing by means of glutaraldehyde-containing primers (Gluma
      Desensitizer, Syntac Primer/Adhesive), or dentin sealing by means of bonding
      agents (Heliobond, ClearfilSE Bond). Additionally, the influence of provisional
      cement (Freegenol) was analyzed after its application and subsequent mechanical
      removal. Bond strength after thermocycling was measured in a shear test (n = 10).
      Data were analyzed with one-way ANOVA, followed by a post-hoc Tukey test (p <
      0.05). RESULTS: Both test cements exhibited significantly lower bond strength to
      freshly ground dentin than the control cement. The desensitization methods did
      not affect the bond strength of the test cements. Furthermore, the sealing
      methods significantly increased the bond strength of both test cements as
      compared to freshly ground dentin. The application and subsequent removal of the
      provisional cement only had a minor influence on the bond strength of the test
      cements. The contamination with provisional cement, however, significantly
      affected the bond strength of the control cement compared to the values achieved
      on freshly ground dentin. CONCLUSION: Desensitization or sealing of dentin have a
      beneficial effect on the bond strength of universal resin cements. The
      application of a provisional cement prior to adhesive cementation exhibits no
      significant influence on the bond strength of the universal resin cements.

PMID- 20157654
TI  - Nanoleakage expression and microshear bond strength in the resin cement/dentin
      interface.
AB  - PURPOSE: The aim of this study was to evaluate dentin sealing ability and
      microshear bond strength of two different resin cements. MATERIALS AND METHODS:
      Resin composite overlays (Estenia C&B) were fabricated and cemented to mid-dentin
      surfaces with either a self-adhesive resin cement (RelyX Unicem) or a resin
      cement with a self-etching primer (Panavia F2.0). After 24 h storage in water,
      the specimens were sectioned, placed into 50% (w/v) ammoniacal silver nitrate
      solution for 24 h, exposed to photodeveloping solution and observed using FE-SEM
      and EDS. Percentage distribution of metallic silver particles in the resin
      cement/dentin interface was calculated using digital image analysis software. In
      addition, small resin overlay cylinders were also bonded to dentin using either
      of the resin cements, and their bonding performance was evaluated with the
      microshear bond strength test. The statistical significance was defined as p <=
      0.05. RESULTS: No statistically significant difference was detected in the
      microshear bond strength between RelyX Unicem and Panavia F2.0 (24.9 +/- 4.8 and
      26.1 +/- 5.3 MPa, respectively, p > 0.05). However, a significant difference was
      detected in silver particle penetration percentage between RelyX Unicem and
      Panavia F2.0 (7.4 +/- 4.6 and 18.7 +/- 8.7 MPa, respectively). The Kruskal-Wallis
      mean ranks for nanoleakage were 6.8 and 14.2, respectively (p < 0.05).
      CONCLUSION: While the bond strengths of the two materials were comparable, the
      self-adhesive resin cement may provide better dentin sealing compared to the self
      etching primer resin cement.

PMID- 20157655
TI  - Marginal adaptation and fracture resistance of root-canal treated mandibular
      molars with intracoronal restorations: effect of thermocycling and mechanical
      loading.
AB  - PURPOSE: This study evaluated the marginal adaptation, fracture modes, and loads
      to failure of different mesio-occlusal- distal (MOD) restorations in root canal
      treated molars in vitro. MATERIALS AND METHODS: Forty mandibular first molars
      were randomly assigned to five groups (n = 8): UTR= untreated, RCT-AM= root-canal
      treated (RCT)+amalgam filling; RCT-COM= RCT+direct composite resin restoration;
      RCTFRC= RCT+composite resin restoration with two layers of multidirectional woven
      glass fibers; RCT-CER= RCT+ceramic inlay. All teeth were subjected to
      thermocycling and mechanical loading (TCML) in a computer-controlled masticator
      (1,200,000 loads, 49 N, 1.7 Hz, 3000 temperature cycles of 5 degrees C to 50
      degrees C). Marginal adaptation was evaluated before and after TCML by scanning
      electron microscopy at 200X at the tooth/restoration interfaces. After TCML, all
      specimens were loaded to failure in a universal testing machine at 0.5 mm/min.
      Failure types were analyzed and scored (reparable: modes 1 and 2; catastrophic:
      modes 3 to 5). Data were analyzed with ANOVA and Bonferroni correction. RESULTS:
      Marginal adaptation decreased significantly after TCML in all groups. The highest
      decrease was observed in RCT-FRC (before: 89.9 +/- 2.2%, after TCML: 49.8 +/-
      11.9%) and the lowest in RCT-CER (before TCML: 90.3 +/- 2.6% after TCML 80.4 +/-
      9.0%). Loads to failure (in N) were in descending order as follows: UTR: 3048 +/-
      905; RCT-CER: 1853 +/- 477; RCT-AM: 1447 +/- 363; RCT-FRC: 1066 +/- 306; RCT-COM
      960 +/- 228. While UTR resulted in statistically higher loads to failure than
      those of all other groups (p < 0.0001), RCT-CER showed significantly higher
      results than those of RCT-COM (p = 0.0014) and RCT-FRC (p = 0.0042). The UTR
      group showed exclusively reparable failures in the form of either superficial
      (mode 1) or complete cusp chipping (mode 2), but all restored teeth exhibited
      catastrophic failures involving fractures along or through the restoration (modes
      3 to 5). CONCLUSION: None of the restored teeth in any group were able to bear
      the same load level as the natural teeth. With regard to marginal adaptation and
      fracture resistance, luted ceramic inlays were advantageous. The integration of
      FRC in the restoration had no positive effect on the fracture resistance. FRC
      application showed a negative effect on marginal adaptation of composite resin
      restorations.

PMID- 20157656
TI  - Marginal quality and fracture strength of root-canal treated mandibular molars
      with overlay restorations after thermocycling and mechanical loading.
AB  - PURPOSE: To evaluate marginal quality, fracture modes, and loads-to-failure of
      different overlay restorations in rootcanal treated molars in a laboratory setup.
      MATERIALS AND METHODS: Thirty-two mandibular first molars were randomly assigned
      to four groups (n = 8): UTR= untreated (control), RCT-COM= root canal treated
      (RCT)+ lab-made composite overlay, RCT-FRC= RCT+composite resin overlay with two
      layers of multidirectional woven glass fibers; RCT-CER: RCT+ceramic overlay. The
      teeth in all groups were subjected to thermocycling and mechanical loading (TCML)
      in a computer-controlled masticator (1,200,000 loads, 49 N, 1.7 Hz, 3000
      temperature cycles of 5 degrees C to 50 degrees C). Marginal adaptation was
      evaluated before and after TCML with scanning electron microscopy at 200X at the
      tooth-to-luting composite (IF1) and luting composite-to restoration (IF2)
      interfaces. After TCML, all specimens were loaded to failure in a universal
      testing machine at 0.5 mm/min. Data were analyzed with ANOVA and Bonferroni
      correction. RESULTS: Marginal adaptation decreased from 93 +/- 3.4 to 82 +/- 6.5
      % at IF1 after TCML (p > 0.001) but the decrease was not significant between the
      groups (p = 0.8130). At IF2, ceramic overlays showed about 10% lower marginal
      adaptation than composite overlays (p < 0.0001). Loads-to-failure (in N) were as
      follows in descending order: RCT-FRC: 3619 +/- 520; UTR: 3048 +/- 905; RCT-COM:
      2770 +/- 457; RCT-CER 2036 +/- 319. RCT-FRC showed significantly higher results
      than those of RCT-COM (p = 0.0077) and RCT-CER (p < 0.0001). Only RCT-CER showed
      significantly lower results than that of the control (p = 0.0019). While the
      fractures in the UTR occurred exclusively above the cementoenamel junction (Mode
      1 and Mode 2) and were rated reparable, RCT-COM and RCT-CER showed exclusively
      catastrophic failures in varying modes (nodes 3 to 5). Only in group RCT-FRC,
      half of the specimens fractured in a reparable fracture mode (modes 1 and 2) with
      veneering composite delamination from the glass-fiber weaver layer. CONCLUSION:
      As cusp-covering overlay restorations in root canal treated molars, composite
      resin overlays with and without fiber reinforcement performed similar to intact
      teeth with varying failure types. While intact teeth failed exclusively in
      reparable modes, all other restorations failed in a catastrophic manner, except
      half of the fiber reinforced composite group.

PMID- 20157657
TI  - Mechanical testing of indirect composite materials directly applied on implant
      abutments.
AB  - PURPOSE: To test the strength to failure and fracture mode of three indirect
      composite materials directly applied onto Ti-6Al-4V implant abutments vs cemented
      standard porcelain-fused-to-metal (PFM) crowns. MATERIALS AND METHODS: Sixty-four
      locking taper abutments were randomly allocated to four groups and were cleaned
      in ethanol in an ultrasonic bath for 5 min. After drying under ambient
      conditions, the abutments were grit blasted and a custom 4-cusp molar crown mold
      was utilized to produce identical crowns (n = 16 per group) of Tescera (Bisco),
      Ceramage (Shofu), and Diamond Crown (DRM) according to the manufacturer's
      instructions. The porcelain-fused-to-metal crowns were fabricated by conventional
      means involving the construction and a wax pattern and casting of a metallic
      coping followed by sintering of increasing layers of porcelain. All crowns were
      loaded to failure by an indenter placed at one of the cusp tips at a 1 mm/min
      rate. Subsequently, fracture analysis was performed by means of stereomicroscopy
      and scanning electron microscopy. One-way ANOVA at 95% level of significance was
      utilized for statistical analysis. RESULTS: The single load to failure (+/- SD)
      results were: Tescera (1130 +/- 239 N), Ceramage (1099 +/- 257 N), Diamond Crown
      (1155 +/- 284 N), and PFM (1081 +/- 243 N). Stereomicroscopy analysis showed two
      distinct failure modes, where the loaded cusp failed either with or without
      abutment/metallic coping exposure. SEM analysis of the fractures showed multiple
      crack propagation towards the cervical region of the crown below a region of
      plastic deformation at the indenter contact region. CONCLUSION: The three
      indirect composites and PFM systems fractured at loads higher than those
      typically associated with normal occlusal function. Although each material had a
      different composition and handling technique, no significant differences were
      found concerning their single load to fracture resistance among composite systems
      and PFM.

PMID- 20157658
TI  - Post-etching cleaning and resin/ceramic bonding: microtensile bond strength and
      EDX analysis.
AB  - PURPOSE: The aim of this study was to evaluate the microtensile bond strength of
      a resin composite bonded to two heat-pressed ceramics after performing different
      post-etching cleaning techniques. MATERIALS AND METHODS: Resin composite
      specimens were bonded to IPS Empress Esthetic (EE) and IPS Empress 2 (E2) heat
      pressed ceramic disks after etching with 10% HF, surface cleaning, silanization
      and application of an unfilled hydrophobic resin. Resin composite specimens were
      fabricated using 4-mm (height) Tygon tubes of 0.8 mm diameter and bonded
      according to the post-etching cleaning technique employed (n = 30): no cleaning
      (NC); air-water spray for 30 s (AWS); 37% phosphoric acid etching for 30 s (PA);
      ultrasonic bath in distilled water for 5 min (UB); PA + UB (PAUB); application of
      a self-etching silane/bonding system Clearfil Silane Kit (CSK). The resin
      composite specimens were subjected to tensile tension at a crosshead speed of 0.5
      mm/min. SEM observation and EDX analysis were performed for each group to
      determine elemental distribution in the samples. RESULTS: Two-way ANOVA with
      random effect showed statistically differences between subgroups for E2, in which
      E2NC only showed bond strength significantly lower than E2AWS and E2BU, as
      indicated by Student's t-test and a contrast method. For EE, subgroups EENC and
      EECSK groups showed statistically significant differences between each other and
      among the other post-etching cleaning technique groups (p < 0.05). CONCLUSION:
      Air-water spray may be used as a post-etching cleaning technique for both
      ceramics. The presence of residues did not significantly reduce the bond strength
      of resin composite to IPS Empress 2 ceramic.

PMID- 20157659
TI  - Static and dynamic failure load of fiber-reinforced composite and particulate
      filler composite cantilever resin-bonded fixed dental prostheses.
AB  - PURPOSE: The aim of this study was to evaluate in vitro the influence of fiber
      reinforcement and luting cement on the static failure load (SFL) and dynamic
      failure load (DFL) of simulated two-unit cantilever resin-bonded fixed dental
      prostheses (RBFDPs). MATERIALS AND METHODS: Forty-six particulate filler
      composite (PFC) beams and 76 fiber-reinforced composite (FRC) beams were
      prefabricated and subsequently luted (RelyX ARC or Panavia F2.0) onto flat ground
      bovine enamel. The SFL of the different specimen types was determined with a peel
      test and the DFL was determined with a rotating cantilever beam fatigue testing
      device. RESULTS: The PFC specimens showed a significantly lower SFL than the FRC
      specimens. The luting cement showed a significant effect on the SFL of the PFC
      specimens, but not with FRC. The DFL of PFC specimens was significantly lower
      than for FRC specimens. The luting cement showed a significant effect on the DFL
      of the PFC specimens, but not so with FRC. With both the SFL and the DFL tests
      all PFC beams fractured, leaving the bonded part on the tooth surface, but FRC
      beams partially debonded from the tooth surface, leaving fibers connected to the
      enamel surface to a varying extent. Coincidentally, the uncured fibers turned out
      to be prone to aging, an effect which has been investigated. CONCLUSION: Within
      the limitations of this study, it can be concluded that PFC without fiber
      reinforcement is not suitable for the fabrication of two-unit cantilever RBFDPs,
      despite the significant effect of the luting cement, but FRC is suitable.

PMID- 20157660
TI  - Effect of water storage on the shear strength and fatigue limit of the reline
      resin bond to denture base resins.
AB  - PURPOSE: This study evaluated the effect of water storage (WS) on the shear bond
      strength (SBS) and shear bond fatigue limit (SBFL) between denture base and
      reline resins. In addition, a possible correlation between SBS and SBFL was
      evaluated. MATERIALS AND METHODS: Two denture base (Lucitone 550-L and Acron MC
      AC) and two reline resins (Ufi Gel Hard- UGH and Tokuso Rebase Fast-TR) were
      selected. Cylinders (20 x 20 mm) of each denture base resin were processed, and
      the reline resins were packed on the bonding surfaces using a split mold (3.5 x
      5.0 mm). Specimens of each denture base-reline resin combination were subjected
      to shear forces (0.5 mm/min) until fracture. A staircase approach was used to
      determine the SBFL. Specimens were submitted to either 10,000 cycles (5.0 Hz) or
      until fracture. For both SBS and SBFL, specimens were tested after relining
      (control) and after 30 days of WS. Data (MPa) were analyzed with 2-way ANOVA and
      Tukey's tests (alpha = 0.05). To test for a possible correlation between the SBS
      and SBFL, a linear regression analysis was performed. RESULTS: WS significantly
      increased (p < 0.05) the SBS of AC-TR and AC-UGH and the SBFL of AC-TR, AC-UGH
      and LUGH. After WS, UGH produced higher (p < 0.05) SBS than TR, regardless of the
      denture base resin used. Regardless of the experimental groups and the denture
      base resins used, UGH produced higher (p < 0.05) SBFL than TR specimens. A strong
      positive linear correlation (r(2) = 0.949) was observed between the SBS and SBFL.
      CONCLUSION: Overall, UGH promoted the highest SBS and SBFL. WS increased the SBS
      and SBFL of the AC relined specimens. A positive correlation was observed between
      the two variables.

PMID- 20157661
TI  - Influence of different curing approaches on marginal adaptation of ceramic
      inlays.
AB  - PURPOSE: To evaluate the effect of different curing protocols on marginal
      adaptation of ceramic inlays after thermomechanical loading (TML). MATERIALS AND
      METHODS: Forty-eight human molars were randomly divided into 6 groups (n = 8).
      After Class II cavity preparation (mod), ceramic inlays (Cerec) were fabricated.
      In groups I to IV, the cavities were conditioned with XP Bond mixed with Self
      Cure Activator (SCA) and the inlays were placed with the luting composite (LC)
      Calibra Mix (dual curing). The teeth in groups V and VI were conditioned with XP
      Bond without SCA and the inlays were placed with Calibra base (only light
      curing). In groups III, IV and V the adhesive was separately light cured prior
      to, and in groups II, IV, V and VI, after the inlay insertion. Before and after
      TML, marginal adaptation was measured using scanning electron microscopy (200X).
      Continuous margins (% of the total) were compared between groups using analysis
      of variance (ANOVA). A Bonferroni correction was applied to correct for multiple
      testing (alpha < 0.005). RESULTS: Light curing after inlay insertion improved
      marginal adaptation on the occlusal interface between LC and enamel
      significantly, regardless of the LC's curing mode. Separate light polymerization
      of XP Bond did not result in superior marginal quality. Investigation of the
      interface between LC and proximal dentin margins showed improved adaptation by
      dual curing the adhesive and LC, irrespective of light application. CONCLUSION:
      Light curing after inlay insertion showed improved marginal adaptation. Using
      dual-curing adhesive and LC, advantages in marginal adaptation between LC and
      dentin were observed.

PMID- 20157662
TI  - Effects of triazine dithione and hydrophobic phosphate monomers on bonding to Ag
      Pd-Cu-Au alloy and titanium with a methacrylic resin-based luting agent.
AB  - PURPOSE: The purpose of the current study was to evaluate the effects of thione
      and phosphate functional monomers on bond strength and durability of a
      methacrylic resin luting agent joined to silver-palladium based alloy and
      titanium. MATERIALS AND METHODS: Disk specimens of two different sizes (10 mm and
      8 mm in diameter by 2.5 mm thickness) were prepared from silver-palladium-copper
      gold (Ag-Pd-Cu-Au) alloy and titanium. The specimens were ground with abrasive
      paper, and divided into four groups based on the following conditions: 1)
      unprimed control; 2) priming with Alloy Primer (thione and phosphate); 3) priming
      with Estenia Opaque Primer (phosphate); and 4) priming with VPrimer (thione). The
      disks were bonded with tri-n-butylborane (TBB)-initiated resin, and shear bond
      strengths were determined both before and after thermocycling. RESULTS: The Alloy
      Primer and V-Primer agents containing a triazine dithione monomer (VTD) bonded
      the Ag-Pd-Cu-Au alloy, whereas the Alloy Primer and Estenia Opaque Primer agents
      containing a hydrophobic phosphate monomer (MDP) bonded titanium. The reduction
      in bond strength after 20,000 thermocycles was not remarkable for the two groups
      (Alloy Primer and Ag-Pd-Cu-Au alloy; V-Primer and Ag-Pd-Cu-Au alloy). CONCLUSION:
      The thione monomer was effective in bonding the Ag-Pd-Cu-Au alloy, whereas the
      phosphate monomer was useful for bonding titanium. The thione did not interfere
      with the bonding of MDP to titanium, and MDP did not negatively affect bonding of
      VTD to the Ag-Pd-Cu-Au alloy. The combinations of two thione primers and the Ag
      Pd-Cu- Au alloy exhibited the best adhesive performance within the limitations of
      the current experiment.

PMID- 20157663
TI  - Clinical evaluation of the posterior composite Quixfil in class I and II
      cavities: 4-year follow-up of a randomized controlled trial.
AB  - PURPOSE: This longitudinal randomized controlled clinical trial evaluated direct
      composite restorations for clinical acceptability as posterior restoratives in
      single- or multi-surface cavities and provides a survey of the 4-year results.
      MATERIALS AND METHODS: Three dentists placed 46 Quixfil (Xeno III) and 50 Tetric
      Ceram (Syntac Classic) composite restorations in stress-bearing Class I and II
      cavities in first or second molars (43 adult patients). Clinical evaluation was
      performed at baseline and after 4 years by 2 other dentists using modified USPHS
      criteria. At the last recall period, 37 Quixfil and 46 Tetric Ceram restorations
      were assessed. RESULTS: A total of 89.2% of Quixfil and 97.8% of Tetric Ceram
      posterior composites were assessed to be clinically excellent or acceptable with
      predominating alfa scores. Up to the 4-year recall, four Quixfil restorations
      failed because of bulk fracture, partial tooth fracture (2x) and postoperative
      symptoms. One Tetric Ceram restoration was lost due to problems with tooth
      integrity. No significant differences between the two composites could be
      detected at 4 years for any of the evaluated clinical criteria (p > 0.05). The
      comparison of restoration performance with time within both groups yielded a
      significant increase in marginal discoloration and decrease in marginal integrity
      for both materials. After 4 years, small restorations exhibited significantly
      less marginal discoloration than large restorations. CONCLUSION: Clinical
      assessment of stress-bearing Quixfil and Tetric Ceram posterior composite
      restorations showed good clinical results with predominantly alfa scores for both
      materials.

PMID- 20157664
TI  - Bond strength of poly(methyl methacrylate) denture base material to cast titanium
      and cobalt-chromium alloy.
AB  - PURPOSE: The shear bond strength of an auto-polymerizing poly(methyl
      methacrylate) denture base resin material to cast titanium and cobalt-chromium
      alloy treated with six conditioning methods was investigated. MATERIALS AND
      METHODS: Disk specimens (10 mm in diameter and 2.5 mm in thickness) were cast
      from pure titanium and cobalt-chromium alloy. The specimens were wet ground to a
      final surface finish of 600 grit, air dried, and treated with the following
      bonding systems: 1) air abraded with 50-70-microm-grain alumina (SAN); 2) air
      abraded with 50-70-microm-grain alumina + conditioned with Alloy Primer (ALP); 3)
      air abraded with 50-70-microm-grain alumina + conditioned with AZ Primer (AZP);
      4) air abraded with 50-70-microm-grain alumina + conditioned with Estenia Opaque
      Primer (EOP); 5) air abraded with 50-70-microm-grain alumina + conditioned with
      Metal Link Primer (MLP), and 6) treated with ROCATEC system (ROC). A denture base
      material (Palapress Vario) was then applied to each metal specimen. Shear bond
      strengths were determined before and after 10,000 thermocycles. RESULTS: The
      strengths decreased after thermocycling in all combinations. Among the treatment
      methods assessed, groups 2 and 4 showed significantly (p < 0.05) enhanced shear
      bond strengths for both metals. In group 4, the strength in MPa (n = 7) after
      thermocycling for cobalt-chromium alloy was 38.3, which was statistically (p <
      0.05) higher than that for cast titanium (34.7). CONCLUSION: Air abrasion
      followed by the application of two primers containing a hydrophobic phosphate
      monomer (MDP) effectively improved the strength of the bond of denture base
      material to cast titanium and cobalt-chromium alloy.

PMID- 20157665
TI  - Adhesive bonding of zirconia with single-liquid acidic primers and a tri-n
      butylborane initiated acrylic resin.
AB  - PURPOSE: The purpose of the current study was to evaluate the effect of acidic
      primers on the bond strength and durability of an acrylic resin luting agent to
      zirconia. MATERIALS AND METHODS: Disk specimens were fabricated from zirconia
      partially stabilized with yttrium oxide (Katana, Noritake Dental Supply). The
      disks were treated with one of the following acidic primers: Acryl Bond (Shofu),
      All Bond II Primer B (Bisco), Alloy Primer (Kuraray), Estenia Opaque Primer
      (Kuraray), Eye Sight Opaque Primer (Kanebo), M.L. Primer (Shofu), MR. Bond
      (Tokuyama Dental), or Super-Bond Liquid (Sun Medical). Unprimed specimens served
      as the control. The disks were bonded with a tri-n-butylborane (TBB)-initiated
      acrylic resin. Shear bond strengths were determined both before and after 10,000
      thermocycles (5 degrees C and 55 degrees C, 1 min dwell time each). RESULTS: The
      pre-thermocycling bond strength ranged from 0.7 MPa to 30.8 MPa, whereas post
      thermocycling bond strength varied from 0.3 MPa to 17.6 MPa. The significantly
      highest post-thermocycling bond strength was obtained when using the Alloy Primer
      and Estenia Opaque Primer agents. CONCLUSION: Within the limitations of the
      current experiment, it can be concluded that application of either the Alloy
      Primer or the Estenia Opaque Primer, both of which contain 10
      methacryloyloxydecyl dihydrogen phosphate (MDP), is recommended for bonding the
      Katana zirconia material with TBB-initiated acrylic resin.

PMID- 20157666
TI  - Two-year clinical evaluation of a self-adhesive luting agent for ceramic inlays.
AB  - PURPOSE: The aim of this prospective randomized controlled clinical trial was to
      evaluate the 2-year clinical performance of a self-adhesive resin cement, RelyX
      Unicem (3M ESPE), used for cementation of ceramic inlays. In addition, the
      influence of selectively acid etching enamel prior to luting on marginal
      integrity, inlay integrity, tooth integrity, sensitivity, and complications of
      the restored teeth was assessed. The hypothesis tested was that there was no
      significant difference in these criteria between restorations with (Etch) or
      without prior enamel acid etching (Non-etch). MATERIALS AND METHODS: Sixty-two
      IPS Empress 2 inlays/onlays were placed in 31 patients by two experienced
      clinicians. The restorations were luted with RelyX Unicem with (=experimental
      group; Etch) or without (=control group; Non-etch) prior enamel etching with
      phosphoric acid. At baseline, 6 months, 1 year and 2 years after placement, the
      restorations were assessed by two calibrated investigators using modified USPHS
      criteria. RESULTS: The recall rate at 24 months was 96.6%. Two restorations were
      clinically unacceptable due to loss of retention, leading to a survival rate of
      96.6% (Kaplan-Meier). No significant difference was noted between the
      experimental group and the control group regarding marginal integrity, inlay
      integrity, tooth integrity, complications and sensitivity (McNemar, p > 0.05). An
      obvious deterioration in marginal adaptation was observed after 24 months as only
      21.7% (Etch = 23.4%; Non-etch = 20%) of the restorations exhibited an excellent
      marginal adaptation compared to 70.7% (Etch = 75%; Non-etch = 66.7%) at baseline.
      In 74.9% of the restorations, small, still clinically acceptable marginal
      deficiencies were observed (Etch = 76.6%; Non-etch = 73.2%). CONCLUSION: The self
      adhesive resin cement RelyX Unicem showed acceptable clinical behavior after two
      years of clinical service. Selective enamel etching prior to luting had no
      significant influence on marginal integrity, inlay integrity, tooth integrity,
      sensitivity or complications of the restored teeth after 24 months. Longer term
      evaluation is needed to confirm this finding.

PMID- 20157667
TI  - Compatibility of five self-etching adhesive systems with two resin luting
      cements.
AB  - PURPOSE: The aim of this study was to evaluate the compatibility between five
      self-etching bonding systems (SEBSs) and two resin luting cements (RLCs) assessed
      by use of an in vitro dentin shear bond test. MATERIALS AND METHODS: The selected
      RLCs were: Variolink II in a dual-cure mode and Multilink in a self-cure mode.
      The SEBSs combined with the RLCs were: two one-step SEBSs (One Up Bond F and Xeno
      III) and three two-step SEBSs (Clearfil SE Bond, Unifil Bond, and Xeno III primer
      coupled with Clearfil SE Bond bonding resin as an experimental combination). One
      hundred fifty human molars were divided into ten groups of fifteen samples each.
      The samples were tested in shear after seven days of storage at 100% RH and 37
      degrees C. After each test, the failure mode was recorded. RESULTS AND
      CONCLUSIONS: Significant differences in shear bond strength (SBS) were observed
      according to both the curing mode of the RLC and the adhesive. The one-step
      systems Xeno III and One Up Bond F revealed a total incompatibility when bonded
      with the chemical-curing RLC. Conversely, the two-step SEBSs were compatible with
      chemical and dual-curing RLC. Failure modes and shear values were in good
      agreement. A positive correlation was found between the pH of the tested adhesive
      solutions or resins and the SBS data

PMID- 20157668
TI  - Microtensile bond strength of three simplified adhesive systems to caries
      affected dentin.
AB  - PURPOSE: The purpose of the study was to determine the microtensile bond strength
      of three different simplified adhesive systems to caries-affected dentin.
      MATERIALS AND METHODS: Fifteen extracted human molars with primary carious
      lesions were ground flat until dentin was exposed. Soft caries-infected dentin
      was excavated with the help of caries detector dye. On the remaining hard dentin,
      a standardized smear layer was created by polishing with 600-grit SiC paper.
      Teeth were divided into three groups and treated with one of the three tested
      adhesives: Adper Scotchbond 1 XT (3M ESPE), a 2-step etch-andrinse adhesive,
      Clearfil S3 Bond (Kuraray), a 1-step self-etching or all-in-one adhesive, and
      Clearfil SE Bond (Kuraray), a 2-step self-etching adhesive. Five-mm-thick
      composite buildups (Z-250, 3M ESPE) were built and light cured. After water
      storage for 24 h at 37oC, the bonded specimens were sectioned into bars (1.0 x
      1.0 mm; n = 20 to 30). Microtensile bond strength of normal dentin specimens and
      caries-affected dentin specimens was measured in a universal testing machine
      (crosshead speed = 1 mm/min). Data were analyzed using two-way ANOVA and Tukey's
      post-hoc test (p < 0.05). RESULTS: No significant differences in bond strength
      values to normal dentin between the three adhesives were found. Adper Scotchbond
      1 XT and Clearfil S3 Bond showed significantly lower bond strength values to
      caries-affected dentin. For Clearfil SE Bond, bond strength values to normal and
      caries-affected dentin were not significantly different. CONCLUSION: All the
      tested simplified adhesives showed similar bond strength values to normal dentin.
      For the tested 2-step etch-and-rinse adhesive and the all-in-one adhesive, the
      bond strength values to caries-affected dentin were lower than to normal dentin.

PMID- 20157669
TI  - In vitro bond strength evaluation of four orthodontic cements.
AB  - PURPOSE: To determine the shear bond strength and adhesive remnant index of
      orthodontic molar bands cemented with four different adhesives. MATERIALS AND
      METHODS: Eighty extracted human third molars were embedded in resin blocks and
      randomly assigned to one of four groups. Four different band cements were
      investigated: Ormco OptiBand, Dentaurum GlasTec, GC Fuji Ortho Band Paste Pak,
      and Unitek Multi-Cure Glass lonomer Orthodontic Band Cement. Bands were cemented
      on the molar crowns, and tensile loads were applied to measure the retentive
      strength. One-way ANOVA was performed for the retentive strength, and the Scheff
      multiple comparison test was applied as a post-hoc test. The Fisher exact test
      was used to determine significant differences in the ARI scores. RESULTS: The
      mean tensile bond strength of GC Fuji Ortho Paste Pak was significantly higher
      than those of all the other groups tested. No statistically significant
      differences were found among the other three groups. CONCLUSION: Among the
      adhesives investigated in the present study, Fuji Ortho Paste Pak resin-modified
      glass-ionomer cement provided the highest tensile bond strength values.

PMID- 20157670
TI  - Shear bond strength of a self-etching primer after 10,000 and 20,000 thermal
      cycles.
AB  - PURPOSE: To determine the effects of thermocycling on shear bond strengths (SBSs)
      of a self-etching primer (SEP)after 10,000 and 20,000 thermal cycles. The tested
      hypothesis was that 10,000 and 20,000 thermal cycles would affect the bond
      strength of metal brackets bonded to enamel with the self-etching primer.
      MATERIALS AND METHODS: Brackets were bonded to bovine incisors with two etching
      protocols. In group CM (conventional method), teeth were etched with 37%
      phosphoric acid for 30 s. In group SEP, a self-etching primer (Transbond Plus, 3M
      Unitek) was applied. Brackets were bonded with light-curing adhesive (Transbond
      XT, 3M Unitek). The SBSs were determined after water storage at 370 degrees C for
      24 h, after 10,000 and 20,000 cycles of thermocycling. RESULTS: For both groups
      (CM and SEP), SBSs decreased with 10,000 and 20,000 thermal cycles. These
      decreased SBSs were significantly different from the values obtained with no
      thermocycling. Highest SBSs were observed with no thermocycling for groups CM and
      SEP (18.6 and 18.0 MPa, respectively). These values were not statistically
      different from each other. Lowest SBSs were obtained with 10,000 and 20,000
      thermal cycles for group SEP (14.2 and 14.7 MPa, respectively). These values were
      significantly different from all other SBSs. CONCLUSION: This study indicates
      that the SEP (Transbond Plus) provides clinically acceptable bond strength values
      compared with the conventional method after 10,000 and 20,000 thermal cycles.

PMID- 20157671
TI  - Bonding of composite resin to dentin using rigid rod polymer modified primers.
AB  - PURPOSE: This study was conducted to evaluate the microtensile bond strength of
      composite resin to dentin with experimental rigid rod polymer (RRP) modified
      primers. RRP fillers are based on long stiff molecules specifically designed to
      create long polymers with restricted chain movement. MATERIALS AND METHODS:
      Experimental primers were fabricated by dissolving RRP into dichloromethane (DCM)
      and further mixing it with monomers: ethylene glycol methacrylate phosphate
      (EGMP), bis[2-(methacryloyloxy)-ethyl]phosphate (BMEP) and
      3(methacryloyloxy)propyltrimethoxysilane (MPS). Eight experimental primers were
      prepared with different proportions for each dentin substrate. A commercial etch
      and-rinse adhesive was used as a control. Surfaces of human molar teeth were wet
      ground occlusally. The experimental primers were applied onto dentin prior to
      light polymerization of the incremental composite resin build-up. After 48 hours
      of water storage, teeth were sectioned and tested with the microtensile tester.
      Fracture surface analysis and contact angle measurements of adhesive resin were
      performed. Scanning electron micrographs were taken. RESULTS: 3-way ANOVA
      revealed that all factors, monomer type, solvent-monomer ratio and RRP, had a
      significant effect (p < 0.05) on bond strength. Primer with a combination of MPS
      and dimethacrylate BMEP revealed higher bond values than a mixture of MPS and
      monomethacrylate EGMP. Increase of the solvent-monomer ratio and addition of RRP
      into primers increased the microTBS. CONCLUSION: The contact angle measurements
      showed that RRP containing primers enhanced adhesive resin penetration into
      dentin similar to that of the control primer. Within the limitations of this
      study, it was concluded that an experimental type of modified RRP-silane
      phosphate-acrylate primer was developed with comparable bonding properties to a
      commercial control.

PMID- 20157672
TI  - The effects of different light-curing units on the clinical performance of
      nanofilled composite resin restorations in non-carious cervical lesions: 3-year
      follow-up.
AB  - PURPOSE: To compare the effects of quartz-tungsten-halogen (QTH) and light
      emitting-diode (LED) curing units on the 3-year clinical performance of a
      nanofilled composite resin in noncarious cervical lesions. MATERIALS AND METHODS:
      Twenty-six patients with at least 2 noncarious cervical lesions were enrolled in
      the study. A total of 154 restorations were placed: half polymerized with QTH and
      half polymerized with LED. Single Bond was used as the adhesive and Filtek
      Supreme was used as the restorative material for all restorations. The
      restorations were assessed by two different examiners using modified Ryge/USPHS
      criteria at baseline and at 6, 12, 24, and 36 months. The survival rates were
      analyzed with the Kaplan-Meier estimator and the Log-Rank test, and the
      statistical analysis was completed using Pearson's chi-square test (p < 0.05).
      RESULTS: Twenty patients were available for recall after 3 years and 114
      restorations were evaluated (recall rate of 74%). The survival rate was 84% for
      QTH and LED polymerized restorations. There were no statistically significant
      differences in survival rates between the light-curing units (p > 0.05). No
      significant differences were observed between QTH and LED polymerized
      restorations in terms of any of the evaluation criteria at the end of 3 years (p
      > 0.05). No color change in the restorations was observed and none of them
      exhibited secondary caries at the end of 3 years. CONCLUSION: Over the 3-year
      study period, both curing units, QTH and LED, produced acceptable clinical
      results in noncarious cervical lesions.

PMID- 20157673
TI  - Bond strength of dental adhesive systems irradiated with ionizing radiation.
AB  - PURPOSE: The aim of the present paper was to determine the effect of different
      types of ionizing radiation on the bond strength of three different dentin
      adhesive systems. MATERIALS AND METHODS: One hundred twenty specimens of 60 human
      teeth (protocol number: 032/2007) sectioned mesiodistally were divided into 3
      groups according to the adhesives systems used: SB (Adper Single Bond Plus), CB
      (Clearfil SE Bond) and AP (Adper Prompt Self-Etch). The adhesives were applied on
      dentin and photo-activated using LED (Lec 1000, MMoptics, 1000 mW/cm2).
      Customized elastomer molds (0.5 mm thickness) with three orifices of 1.2 mm
      diameter were placed onto the bonding areas and filled with composite resin
      (Filtek Z-250), which was photo-activated for 20 s. Each group was subdivided
      into 4 subgroups for application of the different types of ionizing radiation:
      ultraviolet radiation (UV), diagnostic x-ray radiation (DX), therapeutic x-ray
      radiation (TX) and without irradiation (control group, CG). Microshear tests were
      carried out (Instron, model 4411), and afterwards the modes of failure were
      evaluated by optical and scanning electron microscope and classified using 5
      scores: adhesive failure, mixed failures with 3 significance levels, and cohesive
      failure. The results of the shear bond strength test were submitted to ANOVA with
      Tukey's test and Dunnett's test, and the data from the failure pattern evaluation
      were analyzed with the Mann Whitney test (p = 0.05). RESULTS: No change in bond
      strength of CB and AP was observed after application of the different radiation
      types, only SB showed increase in bond strength after UV (p = 0.0267)
      irradiation. The UV also changed the failure patterns of SB (p = 0.0001).
      CONCLUSION: The radio-induced changes did not cause degradation of the
      restorations, which means that they can be exposed to these types of ionizing
      radiation without weakening the bond strength.

PMID- 20157674
TI  - Effect of additional acid etching on bond strength and structural reliability of
      adhesive systems applied to caries-affected dentin .
AB  - PURPOSE: To evaluate the effect of additional acid etching on the microtensile
      bond strength (MUTBS) and Weibull modulus (m) of two adhesive systems applied to
      caries-affected dentin. MATERIALS AND METHODS: Ninety human molars with coronal
      carious lesions were sectioned to produce flat coronal surfaces containing caries
      affected (CAD) and sound dentin (SD). The teeth were allocated to 6 groups: SB
      CT: Control - Single Bond applied according to the manufacturer's instructions;
      SB+15: Single Bond with additional 35% phosphoric acid etching for 15 s; SB+30:
      Single Bond with additional etching for 30 s; CF-CT: Control - Clearfil SE Bond
      applied according to the manufacturer's instructions; CF+15: Clearfil SE Bond
      with additional 35% phosphoric acid etching for 15 s; CF+30: Clearfil SE Bond
      with additional etching for 30 s. Composite crowns were incrementally built up.
      The teeth were sectioned after 24 h in order to produce 2 to 3 slices involving
      each dentin substrate. The slices were trimmed into hourglass-shaped specimens (n
      = 30) and tested in tension at a crosshead speed of 1 mm/min. Data were analyzed
      by three-way ANOVA, Tukey's test (p < 0.05) and Weibull statistics. RESULTS: The
      MUTBS to CAD was lower than to SD, except for SB+30. The additional etching
      increased the MUTBS to CAD. The MUTBS to SD increased with CF, but decreased with
      SB. CAD produced lower values of m with both adhesive systems. SB resulted in
      lower m in sound dentin than CF. The additional etching did not affect the m.
      CONCLUSION: The additional etching increases the MUTBS to CAD, but not enough to
      reach the MUTBS values obtained in SD. The structural reliability of the bond to
      CAD is not affected by the additional etching.

PMID- 20157675
TI  - Effect of different osmotic stimuli on fluid flow before and after self-etching
      adhesive application.
AB  - PURPOSE: To determine the in vitro dentinal fluid movement produced by various
      osmotic stimuli, and evaluate fluid movement across human dentin in response to
      the application of various osmotic stimuli before and after the application of
      self-etching adhesive (Clearfil S3 Bond). MATERIALS AND METHODS: The experiments
      were carried out on 10 extracted premolars. Each tooth was cut transversely below
      to the cementoenamel junction with a diamond disk and water coolant. Dentin was
      exposed at the tip of the buccal cusp by cutting a cavity and was etched with
      acid. The osmotic stimuli were solutions of saturated CaCl2, sugar syrup,
      chocolate, and sweet Thai dessert, used as osmotic test solutions, randomly
      applied to dentin.The fluid flow through dentin obtained after 15 s of
      application of each osmotic stimulus was measured before and after bonding with
      Clearfil S3 Bond single-dose. RESULTS: Before bonding procedures, CaCl2 produced
      peak rates of fluid flow that were significantly higher (p <0.001), when compared
      with normal saline, sugar syrup, chocolate, and sweet Thai dessert. During the
      applications of all osmotic stimuli, the amount of fluid movement across resin
      bonded dentin was significantly lower than that without adhesives. There were no
      significant differences of fluid shifts across resin-bonded dentin obtained
      during the application of any osmotic stimuli. CONCLUSION: It appears that
      different osmotic stimuli produced different rates of outward fluid flow through
      dentin. Clearfil S3 Bond produced similar significant reductions of fluid
      movement in response to osmotic stimulation, irrespective of the chemical
      composition, or the osmotic pressure of stimuli.

PMID- 20157676
TI  - Tensile bond strength of a so-called self-adhesive luting resin cement to dentin.
AB  - PURPOSE: The purpose of the study was to evaluate the bond strength and
      durability of a so-called self-adhesive resin luting cement to human dentin. In
      addition, the influence of a dentin adhesive system on the bond strength was
      tested. MATERIALS AND METHODS: Forty-eight dentin disks from human teeth were
      divided into two groups of 24 specimens.One group was bonded to composite resin
      tubes with the self-adhesive luting cement (RelyX Unicem Aplicap, 3MESPE), in the
      other group the dentin surfaces were conditioned with a three-step dentin
      adhesive system (OptiBondFL, Kerr) prior to bonding with the same cement. Three
      subgroups of eight specimens each were tested for tensile bond strength following
      storage in 37 degrees C tap water for either 3 days or for 150 days with an
      additional 37,500 thermal cycles either between 20 degrees C and 40 degrees C
      ("soft TC") or between 5 degrees C and 55 degrees C ("hard TC"). Statistical
      analyses were performed with the Shapiro-Wilk test, Levene's test, two-way
      analysis of variance (ANOVA) followed by multiple comparisons with the Scheff
      test. RESULTS: Without the dentin adhesive, the mean tensile bond strengths after
      3 days were 7.1 +/- 3.8 MPa; after 150 days/"soft TC" 6.8 + 3.6; and after 150
      days/"hard TC" 5.3 + 4.5 MPa. With the dentin adhesive, the mean bond strengths
      after 3 days were 16.5 +/- 5.5 MPa; after 150 days/"soft TC" 13.1 + 3.9 MPa; and
      after 150 days/"hard TC" 10.1 + 5.2 MPa. CONCLUSION: Regardless of storage
      conditions, the use of a dentin adhesive increased the tensile bond strength of a
      self-adhesive resin luting cement significantly in comparison to the use of the
      luting cement without adhesive.

PMID- 20157677
TI  - Evaluation of dentin hardness and bond strength at different walls of class II
      preparations.
AB  - PURPOSE: The aim of this study was to evaluate the Knoop hardness number (KHN) of
      dentin and the microtensile bond strength (microTBS) at different walls of MOD
      preparations, and the correlation between microTBS and the KHN of dentin.
      MATERIALS AND METHODS: Human molars with MOD preparations were allocated into 3
      groups according to the preparation wall (axial, gingival, pulpal). Each tooth
      was sectioned into halves, resulting in two similar preparation walls: one was
      used for measuring the KHN of dentin and the other for microTBS testing. Flat
      surfaces of the respective walls were obtained by cutting away adjacent walls.
      For the KHN measurement, twelve indentations were performed along the preparation
      wall (50 g/15 s). For microTBS testing, specimens were distributed into 3 groups
      according to the adhesive system (Adper Single Bond Plus/SB, Clearfil SE Bond/SE,
      Adper Prompt/AP). Composite blocks were built over surfaces; specimens were
      sectioned (3 slabs/wall) and trimmed to an hourglass shape (1 mm(2)). RESULTS:
      The KHN of dentin walls was significantly different (ANOVA/Tukey); pulpal wall >
      axial wall > gingival wall. The effect of preparation walls on microTBS was
      dependent on the bonding system (2-way ANOVA/Tukey's test). SB had higher bond
      strength than the other systems at the gingival wall; and higher than SE at the
      axial wall. At the pulpal wall, SE presented a higher mean compared to AP. A
      significant negative correlation between microTBS and KHN was observed at the
      gingival wall. CONCLUSION: It could be concluded that dentin structure can affect
      bond strengths, but the impact of the substrate varies according to the type of
      adhesive system.

PMID- 20157678
TI  - Laser-assisted cavity preparation and adhesion to erbium-lased tooth structure:
      part 2. present-day adhesion to erbium-lased tooth structure in permanent teeth.
AB  - With the introduction of the Er:YAG laser, it has become possible to remove
      enamel and dentin more effectively and efficiently than with other lasers.
      Thermal damage is reduced, especially in conjunction with water spray. Since FDA
      (Federal Drug Administration) approval of the Er:YAG laser in 1997--for caries
      removal, cavity preparation and conditioning of tooth substance - there have been
      many reports on the use of this technique in combination with composite resins.
      Moreover, cavity pretreatment with Er:YAG laser (laser etching) has been proposed
      as an alternative to acid etching of enamel and dentin. Reports evaluating the
      adhesion of glass-ionomer cements to Er:YAG-lased tooth substance are scarce.
      This article reviews the literature regarding adhesion and sealing efficacy using
      different (pre)treatment protocols in association with Er:YAG laser preparation.
      Recent research has shown that lasing of enamel and dentin may result in surface
      and subsurface alterations that have negative effects on both adhesion and seal.
      It is concluded that at present, it is advisable to respect the conventional
      pretreatment procedures as needed for the respective adhesive materials. Although
      the majority of present day reports show that microleakage and bond strength are
      negatively influenced by laser (pre)treatment (compared with conventional
      preparation), there is ongoing discussion of how adhesion is best achieved on
      Er:YAG-lased surfaces.

PMID- 20157679
TI  - Microtensile bond strength of glass fiber posts cemented with self-adhesive and
      self-etching resin cements.
AB  - PURPOSE: To evaluate the bond strength of glass fiber posts to intraradicular
      dentin when cemented with self-etching and self-adhesive resin cements. MATERIALS
      AND METHODS: Forty-eight single-rooted human teeth were decoronated,
      endodontically treated, post-space prepared and divided into 8 groups (n = 6).
      The glass fiber posts used were: Exacto (EA) (Angelus) and everStick (ES)
      (StichTeck), which were cemented with two self-adhesive resin cements: BisCem
      (BIS) (Bisco) and Rely-X Unicem (UNI) (3M/ESPE), and two self-etching resin
      cements: Esthetic Cementing System NAC100 (NAC) (Kuraray) and Panavia-F (PAN)
      (Kuraray). Specimens were thermocycled between 5 degrees C and 55  degrees C for
      1000 cycles and stored in water at 37 degrees C for 1 month. Four 1-mm-thick (in
      cross section) rods were obtained from the cervical region of the roots.
      Specimens were then subjected to microtensile testing in a special machine
      (BISCO; Schaumburg, IL, USA) or a crosshead speed of 0.5 mm/min. Microtensile
      bond strength (MUTBS) data were analyzed with two-way ANOVA and Tukey's tests.
      RESULTS: Means (and SD) of MUTBS (MPa) were: EA/PAN: 10.3 (4.1), EA/NAC: 14 (5.1)
      EA/BIS: 16.4 (4.8), EA/UNI: 19.8 (5.1), ES/PAN: 25.9 (6.1), ES/NAC: 29.1 (7),
      ES/BIS: 28.9 (6), ES/UNI: 30.5 (6.6). ANOVA indicated significant differences
      among the groups (p < 0.001). Mean MUTBS values obtained with ES post were
      significantly higher than those obtained with EA (p < 0.001). For EA, Tukey's
      test indicated that higher MUTBS means were obtained with the self-adhesive resin
      cements (BIS and UNI), which were statistically significantly different (p <
      0.05) from values obtained with the self-etching resin cements (PAN and NAC).
      Different cements had no significant effects on the bond strength values of ES
      post (p > 0.05). MUTBS values obtained with ES post were significantly higher
      than those obtained with EA post irrespective of the resin cement used.
      CONCLUSION: everStick posts resulted in the highest mean MUTBS values with all
      cements. Self-adhesive cements performed well in terms of bond strength.

PMID- 20157680
TI  - Microtensile bond strength distributions of three composite materials with
      different polymerization shrinkages bonded to dentin.
AB  - PURPOSE: To assess the detrimental effects that polymerization contraction causes
      on the interfacial microtensile bond strength (MUTBS) to dentin of three light
      curing resin composites: two conventional bis-GMA-based composite resins (Filtek
      Z250, TPH Spectrum) and a low shrinkage material (Filtek Silorane [SIL]).
      MATERIALS AND METHODS: Flat surfaces of labial dentin were made in 46 bovine
      teeth and restored in single (group A) or in three separate (group B) one
      increment visible-light cured resin composite blocks, with similar locations
      among teeth. After 24 h, restored teeth were sectioned perpendicular to
      interfaces, producing rectangular compound specimens (385 specimens were produced
      in group A, and 132 in group B), and submitted to tension (crosshead speed
      1mm/min) until failure. MUTBS results were adjusted to bonded area and
      transformed to percentages of maximum values within each tooth (PTens). In A
      groups, distances of specimens to the gingival ends of each restoration were
      transformed to PDistances: the percentage of that distance within its specimen.
      RESULTS: Spearman's nonparametric correlation test showed that for Z250, TPH and
      SIL, in A groups, a material's correlation coefficient was positive for the first
      half of restorations (0% to 50% PDistances) and negative for the second (50% to
      100%). For all materials, PTens values in extremes of restorations (pooled 0 and
      100% PDistances) in A groups were smaller than corresponding values in B groups.
      These differences were statistically significantly (Student's t-test) only for
      Z250 and TPH. CONCLUSION: Even in cases of favorable configuration factor,
      polymerization shrinkage in large restorations can reduce interface mechanical
      characteristics. The relevance of this decrease has still to be established.

PMID- 20157681
TI  - Nonlinear visco-elastic finite element analysis of porcelain veneers: a
      submodelling approach to strain and stress distributions in adhesive and resin
      cement.
AB  - PURPOSE: To assess under load the biomechanical behavior of the cementing system
      of feldspathic vs alumina porcelain veneers. MATERIALS AND METHODS: A 3D model of
      a maxillary central incisor, the periodontal ligament (PDL) and the alveolar bone
      was generated. Incisors restored with alumina and feldspathic porcelain veneers
      were compared to a natural sound tooth. Enamel, cementum, cancellous and cortical
      bone were considered isotropic elastic materials; conversely, dentin was
      designated as orthotropic. The nonlinear visco-elatic behavior of the PDL was
      considered. The adhesive layers were modelled using spring elements. A 50-N load
      at a 60-degree angle to the tooth's longitudinal axis was applied and validated.
      Stress concentration in the interfacial volumes of the main models was identified
      and submodelled in a new environment. RESULTS: Regarding tooth structure, strain
      concentrations were observed in the root dentin below the CEJ. As to the cement
      layer, tensile stresses concentrated in the palatal margin of the adhesive
      complex. CONCLUSION: Despite the effects on tooth deformation, the rigidity of
      the veneer did not affect the stress distributions in the cement layer or in the
      adhesive layers. In both cases, the palatal and cervical margins seemed to be the
      most stressed areas.

PMID- 20157682
TI  - Fiber-reinforced composite fixed dental prostheses: a retrospective clinical
      examination.
AB  - PURPOSE: To obtain survival data on 32 fiber-reinforced fixed dental prostheses
      which were inserted in our department and to rate the quality of these
      restorations on the basis of esthetic, biological, and functional parameters.
      MATERIALS AND METHODS: Thirty-two patients with fiber-reinforced fixed dental
      prostheses were included in the study. The fiber frameworks were made of a
      polymer-monomer-preimpregnated continuous unidirectional glass fiber material.
      The survival times, failure events, and clinical parameters were recorded.
      Restorations in function without previous failure were classified as "Overall
      Survival". The classification "Functional Survival" was assigned in the event of
      minor failure and subsequent repair. Loss of the restoration was regarded as
      "Failure". The quality rating was performed using modified USHPS/Ryge criteria.
      RESULTS: The follow-up interval ranged from 2 to 64 months with a median follow
      up time of 18.2 months. Twenty-four restorations were classified as "Overall
      Survival", seven were classified as "Functional Survival", and one was classified
      as "Failure". The overall survival at the median follow-up time was 74.4%. For
      the majority, the quality rating (USHPS/Ryge criteria) yielded clinically
      excellent results in all categories. No restoration was rated as insufficient or
      poor. CONCLUSION: Fiber-reinforced composite fixed dental prostheses provide
      sufficient stability and very good esthetic, biological, and functional
      performance in the case of specific clinical indications.

PMID- 20157683
TI  - Effect of acidic monomers on bonding to SUS XM27 stainless steel, iron, and
      chromium with a tri-n-butylborane-initiated acrylic resin.
AB  - PURPOSE: To evaluate the effects of carboxylic and phosphate functional monomers
      on the bond strength and durability of an acrylic resin joined to a magnetizable
      stainless steel and its component metals. MATERIALS AND METHODS: Disk specimens
      (10 and 8 mm in diameter and 2.5 mm thick) were prepared from SUS XM27 stainless
      steel, high-purity iron, and chromium metals. The specimens were ground with
      abrasive paper, and divided into an unprimed control group and 4 groups primed
      with: 1. Alloy Primer (thione and phosphate); 2. Estenia Opaque Primer
      (phosphate); 3. Mr. Bond (aliphatic carboxylic acid); or 4. Super-Bond C&B Liquid
      (aromatic carboxylic anhydride). The disks were bonded with tri-n-butylborane
      (TBB)-initiated resin, and the shear bond strengths were determined both before
      and after thermocycling (20,000 X, 5 degrees C - 55 degrees C). The debonded
      surfaces were analyzed using Xray diffraction (XRD). RESULTS: The Alloy Primer
      and Estenia Opaque Primer materials containing 10-methacryloyloxydecyl dihydrogen
      phosphate (MDP) effectively bonded the steel (30.3 to 32.4 MPa) and iron (33.6 to
      34.8 MPa), whereas the four acidic primers bonded chromium (24.6 to 32.3 MPa). X
      ray diffractometry detected corroded iron at the debonded interface. CONCLUSION:
      Bearing in mind the limitations of the present study, the use of two primers with
      MDP is recommendable for bonding SUS XM27 steel with TBB-initiated resin. Iron
      was considered to be a corrosive factor at the adhesive interface, although the
      associated bonding characteristics were adequate.

PMID- 20157684
TI  - Primary care summary of the British Thoracic Society Guidelines for the
      management of community acquired pneumonia in adults: 2009 update. Endorsed by
      the Royal College of General Practitioners and the Primary Care Respiratory
      Society UK.
AB  - INTRODUCTION: The identification and management of adults presenting with
      pneumonia is a major challenge for primary care health professionals. This paper
      summarises the key recommendations of the British Thoracic Society (BTS)
      Guidelines for the management of Community Acquired Pneumonia (CAP) in adults.
      METHOD: Systematic electronic database searches were conducted in order to
      identify potentially relevant studies that might inform guideline
      recommendations. Generic study appraisal checklists and an evidence grading from
      A+ to D were used to indicate the strength of the evidence upon which
      recommendations were made. CONCLUSIONS: This paper provides definitions, key
      messages, and recommendations for handling the uncertainty surrounding the
      clinical diagnosis, assessing severity, management, and follow-up of patients
      with CAP in the community setting. Diagnosis and decision on hospital referral in
      primary care is based on clinical judgement and the CRB-65 score. Unlike some
      other respiratory infections (e.g. acute bronchitis) an antibiotic is always
      indicated when a clinical diagnosis of pneumonia is made. Timing of initial
      review will be determined by disease severity. When there is a delay in symptom
      or radiographic resolution beyond six weeks, the main concern is whether the CAP
      was a complication of an underlying condition such as lung cancer.

PMID- 20157685
TI  - [Laryngeal tube suction].
AB  - BACKGROUND: The difficult airway remains a challenge especially in emergencies.
      MATERIALS AND METHODS: The use of laryngeal tube suction in 8 cases involving
      difficult airways in emergencies was reviewed. RESULTS: Use of the laryngeal tube
      was successful in all cases to bridge patients until a secure airway was
      established; insertions were successful at the first attempt and classified as
      easy. In 6 out of 8 patients a secure airway was established by cricothyreotomy
      or by surgical tracheotomy while using the laryngeal tube for oxygenation and
      ventilation of the patient. CONCLUSION: The laryngeal tube allows rapid
      oxygenation in emergency patients with a difficult airway until a secure airway
      can be established. In cases of potentially life saving operations successful
      ventilation via the laryngeal tube might allow the priority of establishing a
      secure airway to be deferred.

PMID- 20157686
TI  - [Perioperative cardiac care for non-cardiac surgery : 2009 Guidelines of the
      European Society of Cardiology].
AB  - Since November 2009, the first European guidelines on perioperative cardiac care
      for non-cardiac surgery have been published by the European Society of Cardiology
      (ESC) and endorsed by the European Society of Anaesthesiology (ESA). The
      following article will describe the most important recommendations of these
      guidelines and discuss the clinically relevant differences to the corresponding
      recommendations of the current guidelines of the American College of Cardiology
      (ACC) and the American Heart Association (AHA).

PMID- 20157687
TI  - [Laparoscopic IPOM technique].
AB  - The laparoscopic intraperitoneal onlay mesh (IPOM) technique for the repair of
      incisional and parastomal hernias has increasingly gained popularity since its
      first description in 1993. The main advantage in comparison with the open
      approach is the reduced incidence of wound complications and the recurrence rate
      also seems to be lower. The laparoscopic technique is based on dissection of the
      complete abdominal wall. The whole original scar must be covered with a broad
      overlap of at least 5 cm. Structures like the falciform ligament and the
      ligamentum teres hepatis must be dissected and the prevesical space must be
      opened to allow adequate fixation and incorporation of the mesh. Meshes used for
      laparoscopic approaches must induce strong and rapid incorporation on the
      parietal side and they should also prevent adhesions on the visceral side. The
      material should allow an overlap of two or more meshes to treat major defects.
      Isolated technical details are not supported by high evidence-based clinical data
      and can only be interpreted as summaries of personal preferences. However with
      respect of three basic aspects, coverage of the whole original scar, broad
      overlap of 5 cm and more and the use of adequate mesh material, very good
      clinical results can be obtained by the laparoscopic IPOM technique.

PMID- 20157688
TI  - [Which abdominal incisions predispose for incisional hernias?].
AB  - Incisional hernias are the most common long-term complication after laparotomy
      with a cumulative incidence up to 20%. Generally all injuries to the integrity of
      the abdominal wall can result in the development of an incisional hernia. Midline
      and transverse incisions cause similar hernia rates. By selection of a sufficient
      closure technique and appropriate suture material as well as taking appropriate
      accompanying treatment (antibiotic prophylaxis) and risk factors into
      consideration, surgery can reduce surgical site infections, wound dehiscence and
      incisional hernias. Results from randomized controlled trials have not yet
      demonstrated a superiority of laparoscope-assisted procedures compared to
      laparotomy for the prevention of incisional hernias. Access through natural
      orifices and removal of specimens through the same approach (NOTES) may prevent
      incisional hernias completely. The approach to the abdominal cavity has to be
      chosen according to the underlying disease of the patient, the anatomical
      conditions and further circumstances (e.g. urgency, extensibility, preservation
      of function of the abdominal wall and safety).

PMID- 20157689
TI  - [Macrophage imaging for differentiation between infectious
      spondylitis/spondylodiscitis and sterile vertebral inflammation: new options for
      the use of USPIO-enhanced MRI beyond lymph node characterization?!].

PMID- 20157690
TI  - [Vertebroplasty for pain reduction in osteoporotic vertebral fracture: possibly
      only a placebo effect?].

PMID- 20157691
TI  - [Acute intestinal inflammation].
AB  - Acute intestinal inflammation is common. In most cases the medical history,
      clinical investigations and laboratory parameters alone are not sufficient for a
      conclusive diagnosis because of the wide variety of differential diagnoses and
      the striking similarity of symptoms. Modern imaging methods can help to clarify
      the diagnosis and multi-slice CT (MSCT) is highly useful in this diagnostic
      dilemma. It is widely available, employs standardized protocols, is cost
      effective and can be performed within an acceptable examination time. MSCT
      enables the location and extension of the underlying pathology to be assessed and
      detection of complications which require immediate therapeutic intervention.

PMID- 20157692
TI  - [Diseases of the hepatobiliary system as a cause of acute abdomen].
AB  - Diseases of the liver and biliary system are common causes of acute abdominal
      pain and gallstone disease predisposes to cholecystitis and cholangiolithiasis.
      Sonography is the method of choice for the assessment of cholecystitis, whereas
      magnetic resonance cholangiopancreaticography (MRCP) is the standard technique to
      detect stones in the common bile duct. Multi-detector computed tomography (MDCT)
      is ideal for detection of associated complications, including abscess formation
      and gall stone ileus. Pyogenic, amebic and fungal liver abscesses are reliably
      diagnosed with MDCT which can also be used for interventional radiologic therapy
      of liver abscesses by percutaneous aspiration or drainage procedures. The second
      most common cause of liver rupture after blunt trauma is spontaneous rupture of
      hypervascular liver tumors (i.e., HCC, adenoma, angiosarcoma) and due to medical
      procedures. Multi-phase contrast-enhanced MDCT can reliably detect active
      bleeding to guide further therapy in these cases.

PMID- 20157693
TI  - [Acute abdomen: clinical background and demands on imaging].
AB  - The term "acute abdomen" does not describe a specific disease entity but is more
      a critical clinical state which incorporates very heterogeneous clinical
      presentations. The prognosis of any disease depends on the time frame from the
      onset of symptoms to the initiation of a specific therapy. For this reason there
      are special expectations by clinicians regarding the diagnostic assessment
      provided by radiology which is expected to deliver an immediate diagnosis
      supporting further therapeutic decisions. Along with the patient's clinical
      history, physical examination and blood tests, radiological diagnostics are
      essential for enabling a specific treatment. From a surgical point of view the
      radiologist is expected to help in differentiating between cases with indications
      for emergency surgery and cases eligible for elective surgery or conservative
      treatment.

PMID- 20157694
TI  - Effects of ascertainment bias and marker number on estimations of barley
      diversity from high-throughput SNP genotype data.
AB  - The capability of molecular markers to provide information of genetic structure
      is influenced by their number and the way they are chosen. This study evaluates
      the effects of single nucleotide polymorphism (SNP) number and selection strategy
      on estimates of germplasm diversity and population structure for different types
      of barley germplasm, namely cultivar and landrace. One hundred and sixty-nine
      barley landraces from Syria and Jordan and 171 European barley cultivars were
      genotyped with 1536 SNPs. Different subsets of 384 and 96 SNPs were selected from
      the 1536 set, based on their ability to detect diversity in landraces or
      cultivated barley in addition to corresponding randomly chosen subsets. All SNP
      sets except the landrace-optimised subsets underestimated the diversity present
      in the landrace germplasm, and all subsets of SNP gave similar estimates for
      cultivar germplasm. All marker subsets gave qualitatively similar estimates of
      the population structure in both germplasm sets, but the 96 SNP sets showed much
      lower data resolution values than the larger SNP sets. From these data we deduce
      that pre-selecting markers for their diversity in a germplasm set is very
      worthwhile in terms of the quality of data obtained. Second, we suggest that a
      properly chosen 384 SNP subset gives a good combination of power and economy for
      germplasm characterization, whereas the rather modest gain from using 1536 SNPs
      does not justify the increased cost and 96 markers give unacceptably low
      performance. Lastly, we propose a specific 384 SNP subset as a standard
      genotyping tool for middle-eastern landrace barley.

PMID- 20157696
TI  - Meta-analysis on insulin treatment for type 2 diabetes: rushed conclusions?

PMID- 20157695
TI  - The Framingham and UK Prospective Diabetes Study (UKPDS) risk equations do not
      reliably estimate the probability of cardiovascular events in a large ethnically
      diverse sample of patients with diabetes: the Action in Diabetes and Vascular
      Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) Study.
AB  - AIMS/HYPOTHESIS: Available multivariable equations for cardiovascular risk
      assessment in people with diabetes have been derived either from the general
      population or from populations with diabetes. Their utility and comparative
      performance in a contemporary group of patients with type 2 diabetes are not well
      established. The aim of this study was to evaluate the performance of the
      Framingham and UK Prospective Diabetes Study (UKPDS) risk equations in
      participants who took part in the Action in Diabetes and Vascular disease:
      Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial. METHODS: The 4
      year risks of cardiovascular disease (CVD) and its constituents were estimated
      using two published Framingham and the UKPDS risk equations in 7,502 individuals
      with type 2 diabetes without prior known CVD at their enrolment in the trial.
      RESULTS: The risk of major CVD was overestimated by 170% (95% CI 146-195%) and
      202% (176-231%) using the two Framingham equations. The risk of major coronary
      heart disease was overestimated by 198% (162-238%) with the UKPDS, and by 146%
      (117-179%) and 289% (243-341%) with the two different Framingham equations,
      respectively. The risks of stroke events were also overestimated with the UKPDS
      and one of the Framingham equations. The ability of these equations to rank risk
      among ADVANCE participants was modest, with c-statistics ranging from 0.57 to
      0.71. Results stratified by sex, treatment allocation and ethnicity were broadly
      similar. CONCLUSIONS/INTERPRETATION: Application of the Framingham and UKPDS risk
      equations to a contemporary treated group of patients with established type 2
      diabetes is likely to substantially overestimate cardiovascular risk.

PMID- 20157697
TI  - Increasing self-reported suicide attempts by adolescents in Greece between 1984
      and 2007.
AB  - PURPOSE: This study examines trends in self-reported suicide attempts by Greek
      adolescents. METHODS: Data were obtained from five nationwide school probability
      surveys, each of approximately 8,000-10,000 adolescents aged 14-18 years, carried
      out from 1984 to 2007. Students answered an anonymous questionnaire in their
      classrooms supervised by research assistants. Logistic regression analysis used
      as dependent variable any self-reported suicide attempts and as independent
      variables basic sociodemographic information and the year of the survey. RESULTS:
      Self-reported suicide attempts doubled in prevalence from 7.0% in 1984 to 13.4%
      in 2007. Female gender (odds ratio OR 2.49, 95% confidence interval CI 2.30
      2.71), living in a single parent family (OR 1.91, CI 1.73-2.11), lower paternal
      education (OR 1.20, CI 1.10-1.31) and living in a major city (OR 1.17, CI 1.08
      1.27 for Greater Athens and OR 1.13, CI 1.00-1.28 for Thessaloniki) were
      significantly associated with suicide attempts. A larger increase among males,
      from 2.4 to 8.4%, compared to females (11.5 to 17.9%) contributed to a decrease
      in gender differences. CONCLUSIONS: Changes in Greek society during the last 30
      years, including loosening of family ties, increased drug use and stress because
      of the demands of school work, are hypothesised to have had an impact on the
      increasing trend in suicide attempts among adolescents.

PMID- 20157698
TI  - Employing high-resolution materials characterization to understand the effects of
      Pd nanoparticle structure on their activity as catalysts for olefin
      hydrogenation.
AB  - Recent developments in nanotechnology have led to the production of new materials
      with a wide array of applications, particularly in catalysis. Because of their
      small size, nanoparticles have a maximized surface-to-volume ratio, thus making
      them attractive targets for use as catalytic structures; however, the number of
      analytical techniques available to fully characterize materials on such a size
      scale is quite limited. As a result, a complete understanding of the entire
      nanoparticle structure remains unclear, especially when considering the active
      structural motif from which the specific activity arises. Metallic Pd materials
      have been widely studied due to their immense potential as catalysts for
      reactions such as olefin hydrogenation and C-C bond synthesis. These materials
      require surface passivants to act as ligands and stabilize the nanoparticles
      against aggregation and bulk formation. These ligands have the added value to
      function as gates that selectively allow reagents to reach the active surface of
      the Pd nanoparticles for chemical turnover. This accounts for the observed
      selectivities of the catalysts with the corresponding changes in the turnover
      frequency values. Here we present a broad overview of recent advances in the use
      of Pd nanoparticles for the industrially important hydrogenation reaction with a
      focus on characterizing and understanding the base structural effects that give
      rise to the catalytic activity.

PMID- 20157699
TI  - Asymmetrical intermanual transfer of learning in a sensorimotor task.
AB  - We examined the influence of the hand employed in sensorimotor learning on the
      acquired sequence knowledge in a serial reaction time task. Right-handed subjects
      trained either with the dominant or with the nondominant hand sequences of finger
      postures in response to a corresponding stimulus sequence. In the course of
      training, they were repeatedly asked to switch to the opposite hand, either
      responding to the original stimulus sequence with nonhomologues fingers or to the
      mirror-ordered sequence of stimuli with homologues fingers. When the right hand
      was used at acquisition, transfer to the same stimulus sequence increased with
      practice. In contrast, when the left hand was trained, transfer to the homologues
      finger sequence increased with practice. The results indicate qualitative
      differences in the acquired sequence knowledge controlling the dominant and the
      nondominant arm systems.

PMID- 20157700
TI  - The intermuscular 3-7 Hz drive is not affected by distal proprioceptive input in
      myoclonus-dystonia.
AB  - In dystonia, both sensory malfunctioning and an abnormal intermuscular low
      frequency drive of 3-7 Hz have been found, although cause and effect are unknown.
      It is hypothesized that sensory processing is primarily disturbed and induces
      this drive. Accordingly, experimenter-controlled sensory input should be able to
      influence the frequency of the drive. In six genetically confirmed myoclonus
      dystonia (MD) patients and six matched controls, the low-frequency drive was
      studied with intermuscular coherence analysis. External perturbations were
      applied mechanically to the wrist joint in small frequency bands (0-4, 4-8 and 8
      12 Hz; 'angle' protocol) and at single frequencies (1, 5, 7 and 9 Hz; 'torque'
      protocol). The low-frequency drive was found in the neck muscles of 4 MD
      patients. In these patients, its frequency did not shift due to the perturbation.
      In the torque protocol, the externally applied frequencies could be detected in
      all controls and in the two patients without the common drive. The common low
      frequency drive was not be affected by external perturbations in MD patients.
      Furthermore, the torque protocol did not induce intermuscular coherences at the
      applied frequencies in these patients, as was the case in healthy controls and in
      patients without the drive. This suggests that the dystonic 3-7 Hz drive is
      caused by a sensory-independent motor drive and sensory malfunctioning in MD
      might rather be a consequence than a cause of dystonia.

PMID- 20157701
TI  - Rofecoxib, but not celecoxib, increases the risk of thromboembolic cardiovascular
      events in young adults-a nationwide registry-based study.
AB  - PURPOSE: To examine the risk of thromboembolic cardiovascular events in users of
      coxibs and NSAIDs in a nationwide cohort. METHODS: Data were synchronised from
      three nationwide databases, the Icelandic Medicines Registry (IMR), The Icelandic
      National Patient Registry (INPR) and the Registry for Causes of Death at
      Statistics Iceland (RCD), for prescriptions for NSAIDs or coxibs with respect to
      hospitalisation for unstable angina pectoris, myocardial infarction and cerebral
      infarction over a 3-year period. The Cox proportional hazards model and Poisson
      regression were used to analyse the data. RESULTS: A total of 108,700 individuals
      received prescriptions for NSAIDs or coxibs (ATC code M01A), of whom 78,539
      received one drug only (163,406 person-years). Among those receiving only one
      drug 426 individuals were discharged from hospital with endpoint diagnoses. In
      comparison to diclofenac, the incidence ratios, adjusted for age and gender, were
      significantly higher for cerebral infarction (2.13; 95% CI 1.54-2.97; P < 0.001),
      for myocardial infarction (1.77; 95% CI 1.34-2.32; P < 0.001) and for unstable
      angina pectoris (1.52; 95% CI 1.01-2.30; P = 0.047) for patients who used
      rofecoxib. For naproxen users, the incidence ratio was 1.46 for myocardial
      infarction (95% CI 1.03-2.07; P = 0.03), but was reduced in ibuprofen users
      (0.63; 95% CI 0.40-1.00; P = 0.05). The youngest users of rofecoxib (< or =39
      years) had the highest hazard ratio (HR) for cardiovascular events (8.34; P <
      0.001), while those > or =60 years had a lower but still significantly elevated
      HR (1.35; P = 0.001). CONCLUSION: This Icelandic nationwide registry-based study
      amounting to 163,406 patient-years showed increased risk of cardiovascular
      events, i.e. cerebral infarction, myocardial infarction and unstable angina
      pectoris, among rofecoxib and naproxen users in comparison to diclofenac users.
      The added risk was most pronounced in young adults using rofecoxib.

PMID- 20157703
TI  - Why US should not be performed for the diagnosis of intussusception.

PMID- 20157702
TI  - Analysis of urinary calculi composition by infrared spectroscopy: a prospective
      study of 625 patients in eastern China.
AB  - Urolithiasis is a common urologic disease whose prevalence is about 1-20% and
      increasing throughout the world. The recurrence rate after treatment is more than
      50%. Urinary stone analysis is important in determining the possible etiology and
      the pathophysiology of stone formation. A better understanding of the stone
      composition may help prevent urinary stone formation. From March 2007 to December
      2008, physical analysis of urolithiasis in patients who lived in eastern China
      for more than 5 years and underwent surgery or shock wave lithotripsy in our
      hospital or passed their stones spontaneously was carried out using the Fourier
      transform infrared spectroscopy (FT-IR). Clinical and demographic findings were
      evaluated and compared with the stone components. Stone analysis was performed in
      625 patients. The FT-IR evaluation showed that 234 (37.4%) were pure, and the
      most frequent was calcium oxalate (33.9%), followed by calcium phosphate (2.7%),
      and uric acid (0.8%). 391 (62.6%) were mixed stone, calcium oxalate (43.2%) was
      the most commonly major component, followed by calcium phosphate (16.3%), cystine
      (1.3%), uric acid (1.1%), and struvite (0.6%). Uric acid (p = 0.029) was the
      major component found more frequently in men, while struvite (p = 0.037) was more
      frequent in women. Uric acid (p = 0.031) was more common in lower urinary tract
      stones, and its formers with the mean age of 55 years were older than those with
      other components (p = 0.039). In eastern China, the most commonly found pure
      stone was calcium oxalate, while the most frequent mixed stone was calcium
      oxalate and calcium phosphate mixture. Stone location, gender, and age may
      influence stone component.

PMID- 20157705
TI  - Imaging findings of intravascular papillary endothelial hyperplasia presenting in
      extremities: correlation with pathological findings.
AB  - OBJECTIVE: To describe magnetic resonance imaging (MRI) and ultrasound (US)
      findings of intravascular papillary endothelial hyperplasia (IPEH) arising in
      extremities. MATERIALS AND METHODS: Six patients with IPEH confirmed by surgical
      resection were reviewed retrospectively. Before resection, 3 patients underwent
      both MRI and US and 3 patients underwent only MRI. Two radiologists
      retrospectively reviewed MR/US imaging results and correlated them with
      pathological features. RESULTS: The 6 IPEHs were diagnosed as 4 mixed forms and 2
      pure forms. The pre-existing pathology of four mixed forms was intramuscular or
      intermuscular hemangioma. By MRI, the mixed form of IPEH (n = 4) revealed iso- to
      slightly high signal intensity containing nodule-like foci of high signal
      intensity on T1-weighted images (T1WI) and high signal intensity-containing
      nodule-like foci of low signal intensity on T2-weighted images (T2WI). The pure
      form of IPEH (n = 2) showed homogeneous iso- signal intensity on T1WI and high
      and low signal intensity containing nodule-like foci of low signal intensity on
      T2WI. On gadolinium-enhanced fat-suppressed T1WI, 50% of cases (n = 3: mixed
      forms) revealed peripheral, septal, and central enhancement. The other IPEHs (n =
      3: 1 mixed and 2 pure forms) showed peripheral and septal enhancement or only
      peripheral enhancement. By US, two mixed forms of IPEH showed well-defined
      hypoechoic masses containing hyperechoic septa and central portion with
      vascularities. One pure form of IPEH was a homogeneous hypoechoic mass with
      septal and peripheral vascularities on color Doppler imaging. The foci of high
      signal intensity on T1WI, foci of low signal intensity on T2WI, and non-enhancing
      portions on MRI and the hypoechoic portion on US were histopathologically
      correlated with thrombi and the peripheral/septal or central enhancing areas on
      MRI, hyperechoic septa and the central portion on US, and septal/central or
      peripheral vascularities on color Doppler imaging corresponded to hypertrophic
      papillary epithelium and a fibrovascular core. CONCLUSIONS: Even though imaging
      findings of the pure form of IPEH are rather nonspecific, the mixed form of IPEH
      should be considered a possible diagnosis when a well-defined mass with T2
      hyperintense signal containing nodule-like foci of low signal intensity, T1 iso-
      to slightly hyperintense signal containing nodule-like foci of high signal
      intensity, and peripheral/septal or central enhancement on MRI is seen in
      extremities, along with the US finding of a hypoechoic mass containing
      hyperechoic septa with vascularities.

PMID- 20157706
TI  - 68Ga-labelled recombinant antibody variants for immuno-PET imaging of solid
      tumours.
AB  - PURPOSE: Recombinant antibodies isolated from human antibody libraries have
      excellent affinities and high target specificity. As full-length IgGs are cleared
      inadequately slowly from the circulation, the aim of this work was to figure out
      which kind of recombinant antibody fragment proves to be appropriate for imaging
      epithelial cell adhesion molecule (EpCAM)-expressing tumours with the short
      living radioisotope (68)Ga. METHODS: In order to combine the promising tumour
      targeting properties of antibodies with (68)Ga, four antibody variants with the
      same specificity and origin only differing in molecular weight were constructed
      for comparison. Therefore, the binding domains of a single-chain fragment
      variable (scFv) isolated from a human naive antibody library were modified
      genetically to construct the respective full-length IgG, the tria- and diabody
      variants. These molecules were conjugated with the bifunctional chelating agent
      N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid
      (HBED-CC) to enable (68)Ga labelling at ambient temperature and compared in
      biodistribution and immuno-PET imaging experiments. RESULTS: The antibody
      variants with identical specificity proved to have the correct molecular weight,
      high binding affinity and specificity to their antigen, EpCAM. Radiometal
      complexation was efficiently performed at room temperature leading to (68)Ga
      labelled antibodies with unchanged binding properties compared to the original
      antibody variants. The best targeting properties were obtained with the scFv and
      especially with the diabody. The triabody showed higher absolute tumour uptake
      but only moderate clearance from circulation. CONCLUSION: The antibody variants
      differed considerably in normal organ uptake, clearance from circulation and
      tumour accumulation. The data demonstrate the feasibility of imaging solid
      tumours with the (68)Ga-labelled diabody format. This type of recombinant protein
      might be a promising carrier even for the short-lived radiometal (68)Ga to
      support e.g. the management of immunotherapy which may provide important
      information regarding receptor expression of solid tumours.

PMID- 20157707
TI  - Targeted alpha-radionuclide therapy of functionally critically located gliomas
      with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial.
AB  - PURPOSE: Functionally critically located gliomas represent a challenging subgroup
      of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot
      be applied, because radical treatment and preservation of neurological function
      are contrary goals. The successful targeting of gliomas with locally injected
      beta radiation-emitting (90)Y-DOTAGA-substance P has been shown previously.
      However, in critically located tumours, the mean tissue range of 5 mm of (90)Y
      may seriously damage adjacent brain areas. In contrast, the alpha radiation
      emitting radionuclide (213)Bi with a mean tissue range of 81 microm may have a
      more favourable toxicity profile. Therefore, we evaluated locally injected
      (213)Bi-DOTA-substance P in patients with critically located gliomas as the
      primary therapeutic modality. METHODS: In a pilot study, we included five
      patients with critically located gliomas (WHO grades II-IV). After diagnosis by
      biopsy, (213)Bi-DOTA-substance P was locally injected, followed by serial
      SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the
      functional outcome was evaluated. RESULTS: Targeted radiopeptide therapy using
      (213)Bi-DOTA-substance P was feasible and tolerated without additional
      neurological deficit. No local or systemic toxicity was observed. (213)Bi-DOTA
      substance P showed high retention at the target site. MR imaging was suggestive
      of radiation-induced necrosis and demarcation of the tumours, which was validated
      by subsequent resection. CONCLUSION: This study provides proof of concept that
      targeted local radiotherapy using (213)Bi-DOTA-substance P is feasible and may
      represent an innovative and effective treatment for critically located gliomas.
      Primarily non-operable gliomas may become resectable with this treatment, thereby
      possibly improving the prognosis.

PMID- 20157708
TI  - Evaluation of the kappa-opioid receptor-selective tracer [(11)C]GR103545 in awake
      rhesus macaques.
AB  - PURPOSE: The recent development in radiosynthesis of the (11)C-carbamate function
      increases the potential of [(11)C]GR103545, which for the last decade has been
      regarded as promising for imaging the kappa-opioid receptor (kappa-OR) with PET.
      In the present study, [(11)C]GR103545 was evaluated in awake rhesus macaques.
      Separate investigations were performed to clarify the OR subtype selectivity of
      this compound. METHODS: Regional brain uptake kinetics of [(11)C]GR103545 was
      studied 0-120 min after injection. The binding affinity and opioid subtype
      selectivity of [(11)C]GR103545 was determined in cells transfected with cloned
      human opioid receptors. RESULTS: In vitro binding assays demonstrated a high
      affinity of GR103545 for kappa-OR (K(i) = 0.02 +/- 0.01 nM) with excellent
      selectivity over mu-OR (6 x 10(2)-fold) and) delta-OR (2 x 10(4)-fold). PET
      imaging revealed a volume of distribution (V(T)) pattern consistent with the
      known distribution of kappa-OR, with striatum = temporal cortex > cingulate
      cortex > frontal cortex > parietal cortex > thalamus > cerebellum. CONCLUSION:
      [(11)C]GR103545 is selective for kappa-OR and holds promise for use to
      selectively depict and quantify this receptor in humans by means of PET.

PMID- 20157709
TI  - (18)F-FDG PET patterns and BAL cell profiles in pulmonary sarcoidosis.
AB  - PURPOSE: Bronchoalveolar lavage (BAL) and (18)F-fluorodeoxyglucose ((18)F-FDG)
      PET can both demonstrate sarcoid activity. To assess whether metabolic activity
      imaged by (18)F-FDG PET represents signs of disease activity as reflected by BAL,
      (18)F-FDG PET patterns were compared with BAL cell profiles. METHODS: In this
      retrospective analysis, 77 newly diagnosed pulmonary sarcoidosis patients
      underwent BAL and (18)F-FDG PET. Based on (18)F-FDG PET, patients were diagnosed
      with exclusively mediastinal/hilar activity (group A) and activity in the lung
      parenchyma (group B). Per group, BAL lymphocytes (%), CD4/CD8 ratio,
      CD103(+)CD4(+)/CD4(+) ratio and neutrophils (%) were compared with the extent of
      metabolic activity expressed as the maximum standardized uptake value (SUV(max)).
      Additionally, SUV(max) and BAL parameters per radiographic stage were analysed.
      RESULTS: Overall, the SUV(max) in the lung parenchyma correlated with neutrophils
      and SUV(max) of the mediastinum/hila correlated with the CD4/CD8 ratio. In both
      groups, a significant, negative correlation between the SUV(max) of the
      mediastinum/hila and the CD103(+)CD4(+)/CD4(+) ratio was found. In group B, the
      SUV(max) of the mediastinum/hila correlated with the CD4/CD8 ratio, while the
      SUV(max) in the lung parenchyma correlated with the CD103(+)CD4(+)/CD4(+) ratio
      and neutrophils. Significant differences were found in the SUV(max), CD4/CD8
      ratio, CD103(+)CD4(+)/CD4(+) ratio and neutrophils between the radiographic
      stages. The SUV(max) of the lung parenchyma was positively related to the
      radiographic stage, while the SUV(max) of the mediastinum/hila and CD4/CD8 ratio
      were inversely related. CONCLUSION: (18)F-FDG PET correlates with the CD4/CD8
      ratio and neutrophils, suggesting that (18)F-FDG PET represents this specific
      cell profile in BAL. High SUV(max) values of the lung parenchyma may therefore
      correlate with more severe parenchymal involvement, particularly when accompanied
      by a low SUV(max) of the mediastinum/hila.

PMID- 20157710
TI  - Variation in the blood supply of the sinus node.
AB  - PURPOSE: The purpose of the study was to examine the anatomical variations in the
      blood supply to the sinus node. METHODS: Gross anatomical examination and
      angiographic evaluation were performed in 400 human hearts derived from victims
      of various accidents. RESULTS: The sinus node artery was a branch of the right
      coronary artery in 245 cases, the left circumflex in 147 cases, and both coronary
      arteries in 8 cases. In one subject, two sinus node arteries were found to arise
      from the left circumflex artery, a finding never reported before. CONCLUSIONS:
      Anatomic and postmortem angiographic findings of a previously unreported case
      where the sinus node is perfused by two sinus node arteries originating from the
      left circumflex coronary artery are demonstrated. Knowledge of this anatomical
      variation is useful for anatomists and of clinical significance for the
      interventional cardiologists and mainly for the cardiac surgeons in planning the
      surgical procedures.

PMID- 20157711
TI  - An early phase II trial of S-1 in Japanese patients with cytokine-refractory
      metastatic renal cell carcinoma.
AB  - PURPOSE: S-1, an oral anticancer agent, contains tegafur (FT), 5-chloro-2,4
      dihydroxypyridine (CDHP), and potassium oxonate (Oxo) at a molar ratio of
      FT:CDHP:Oxo = 1:0.4:1. The aim of this trial was to investigate the efficacy and
      safety of S-1 in Japanese patients with cytokine-refractory metastatic renal cell
      carcinoma (RCC). METHODS: We conducted a non-randomized, open-label trial in
      Japanese patients with metastatic RCC who had received nephrectomy and had failed
      cytokine-based immunotherapy. The primary endpoint was response rate. S-1 40-60
      mg based on the body surface area was administered twice daily (80-120 mg/day)
      for 4 consecutive weeks, followed by a 2-week rest period; cycles were repeated
      every 6 weeks. Patients continued treatment until disease progression,
      unacceptable toxicity, or withdrawal of consent. RESULTS: A total of 20 eligible
      patients were enrolled. Among these, 3 patients had partial response, yielding
      objective response rate of 15%; 13 patients had no change; 4 patients had
      progressive disease. The median time-to-progression and median overall survival
      were 12.0 and 25.7 months, respectively. The initial adverse event was generally
      mild to moderate in severity. The most common grade 3/4 drug-related
      hematological and non-hematological adverse events were neutropenia (20.0%) and
      anorexia (20.0%), respectively. CONCLUSIONS: S-1 is active and well tolerated for
      the treatment of cytokine-refractory metastatic RCC.

PMID- 20157712
TI  - Radiographic hand osteoarthritis and serum levels of osteocalcin: cross-sectional
      study.
AB  - The objective of this study is to evaluate the association between radiographic
      hand osteoarthritis and serum level of osteocalcin. The study population
      comprised Chuvashians (285 males, age 47.38 +/- 16.79; 265 females, age 48.55 +/-
      15.94 years). OA was evaluated for 14 joints of each hand using Kellgren and
      Lawrence (K-L), joint space narrowing (JSN) and osteophytes (OS) scores. Plasma
      intact osteocalcin was measured in 550 individuals by immunoradiometric assay
      using ELSA-OSTEO kit. Statistical analyses included multiple linear and logistic
      regressions. 51.64% of studied individuals had at least one finger joint affected
      at K-L > or = 2 level. JSN at the level > or = 2 was found in 9.82% and OS > or =
      2 was found in 35.09% of the studied individuals. Osteocalcin showed a modest,
      but statistically significant, association with the number of affected joints
      according the K-L scale (beta = 0.082, p = 0.015), JSN scale (beta = 0.097, p =
      0.025) and OS scale (beta = 0.078, p = 0.029). No significant association was
      found between the presence of at least one affected joint (K-L > or = 2 or OS >
      or = 2) and serum level of osteocalcin. Presence of at least one joint with space
      narrowing > or = 2 was significantly associated with serum level of osteocalcin
      (beta = 0.052, p = 0.023). In this cross-sectional population-based study, we
      found that serum level of osteocalcin is positively associated with severity of
      hand OA, measured by K-L, JSN and OS scales.

PMID- 20157713
TI  - Muscular waves contribute to gliding rate in the freshwater gastropod Lymnaea
      stagnalis.
AB  - This study revises the mechanisms of ciliary locomotion and demonstrates muscular
      contribution to locomotion rate in Lymnaea stagnalis. L. stagnalis sticks to the
      substratum by the foot sole and moves smoothly with no visible contractions of
      the foot. A ciliated epithelium covering the sole is underlain by smooth muscle
      cells containing giant mitochondria. It is shown here that slow (basal) locomotor
      activity (measured as the flow rate of physiological saline over isolated sole)
      appears spontaneously or is induced by 10(-8)-10(-7) M 5-HT. 5-HT (10(-7)-10(-4)
      M) facilitates locomotor activity dose-dependently, and KCN (an inhibitor of
      mitochondrial respiration) decreases these effects to the basal level. 5-HT and
      KCN have no effect on the frequency of ciliary beat (stroboscopic measurements),
      and blockers of anaerobic glycolysis inhibit ciliary motility. Under anaerobic
      conditions locomotion of a snail is slow and insensitive to 5-HT in contrast to
      that in aerobic environments. It is concluded that glycolysis supplies energy to
      ciliated cells and respiration to sole muscle cells; 5-HT stimulates ciliary
      beating in an all-or-none fashion and muscular waves in a dose-dependent manner;
      cilia provide slow (basal) gliding, and locomotory rate up to 80% above the basal
      level is determined by muscular waves.

PMID- 20157714
TI  - Factors influencing spinal canal stenosis in patients with long-term controlled
      hydrocephalus treated with cerebrospinal fluid shunt.
AB  - PURPOSE: Spinal canal stenosis (CS) occurs in patients with hydrocephalus who are
      treated with cerebrospinal fluid (CSF) shunting. The pathophysiology of CS
      comprises CSF overdrainage. We analyzed the incidence of CS and the factors
      causing it. METHODS: Thirty-three patients who underwent ventriculoperitoneal
      shunt during childhood visited the Outpatient Department in Yamaguchi University
      Hospital in 2006. Diameters of spinal canal at C(4) were measured. Treatment
      procedure, age, and type of hydrocephalus in the patients with CS were compared
      with those without CS. RESULTS: Of the 33 patients, 10 (30.3%) presented CS, and
      two (6.1%) were symptomatic. A low-pressure valve caused CS with a significantly
      higher incidence than a medium- or high-pressure valve (60.0% vs. 17.4%, P <
      0.05). Although the difference was not significant, the average age of shunt
      insertion for a patient with CS was slightly less (0.87 +/- 0.99) than for a
      patient without CS (1.63 +/- 1.58). No differences in the CS incidence were
      observed between obstructive and communicating hydrocephalus. CONCLUSION: In
      order to prevent CS, the hydrocephalus should be appropriately controlled by
      using a medium- or high-pressure valve until the diameter of the spinal canal
      reaches the required level. Adjustment of the programmable valve with the
      patient's growth should be ideal.

PMID- 20157715
TI  - Bilateral papillary cystadenoma of the mesosalpinx: a rare manifestation of Von
      Hippel-Lindau disease.
AB  - We report a rare case of a woman with bilateral papillary cystadenomata of the
      broad ligament with von Hippel-Lindau disease (VHL) (other manifestations:
      capillary hemangioblastomas of the spinal cord). Patient surveillance is
      important, because in the course of VHL-associated tumors malignant lesions may
      arise that are relevant for the prognosis.

PMID- 20157716
TI  - Radiochemotherapy versus radiotherapy in locally advanced cervical cancer: a meta
      analysis.
AB  - OBJECTIVE: The objectives of this review are to compare the effectiveness and
      safety of radiochemotherapy (RTCT) with radiotherapy (RT) alone in locally
      advanced cervical cancer (LACC). DATA SOURCES: We comprehensively searched the
      Cochrane library, Medline, EMBASE, Chinese biomedicine literature database,
      Chinese scientific full-text database and Chinese journal full-text database for
      relevant articles. The computer search was supplemented with a manual search of
      reference lists for all available review articles. Also reference lists of the
      included studies were reviewed. RESULTS: We included 18 randomized trials
      involving 3,517 patients. Meta-analysis results are as follows: the response
      rate, 3 and 5-year survival rates were significantly better in patients in the
      RTCT group than in RT group. As adverse effects, limited evidence suggests that
      there was no significant difference between the two groups with regard to
      rectitis, cystitis, nausea and vomiting. But RTCT group has higher incidence
      rates than RT group in gastrointestinal, myelosuppression and leucopenia.
      CONCLUSION: The combination of radiotherapy and chemotherapy was more effective
      for LACC than radiotherapy alone. There was no significant difference between the
      RTCT regimen group and RT regimen group with regard to adverse effects.

PMID- 20157717
TI  - Leiomyo-adenomatoid tumor of the uterus: a distinct morphological entity?
AB  - INTRODUCTION: The morphologic and immunohistochemical findings of a well
      circumscribed leiomyoadenomatoid tumor located in the posterior uterine wall are
      reported. CASE REPORT: The patient was a 55-year-old white woman who complained
      of peri/postmenopausal and irregular bleeding during the past 4 months. The
      adenomatoid component was intermingled with bland smooth muscle fascicles and was
      composed of vacuolated cells, tubules, and slit-like structures crossed by
      epithelial bridges. Immunohistochemistry revealed positivity to epithelial and
      mesothelial markers in the adenomatoid component and strong immunoreaction for
      smooth muscle markers in the leiomyomatous one. CONCLUSIONS: The well-defined
      circumscription and the presence of mesothelial component intermingled with the
      leiomyomatous proliferation favors the hypothesis that a leiomyo-adenomatoid
      tumor should be considered as a subtype of adenomatoid tumor with distinctive
      morphological features. Only four previous cases of this rare neoplasm have been
      reported to date, one in the epydidimis and the other three cases in the uterine
      wall, one of them affecting also to the right ovary.

PMID- 20157718
TI  - Management of maternal hydrocephalus requires replacement of ventriculoperitoneal
      shunt with ventriculoatrial shunt: a case report.
AB  - BACKGROUND: Women with ventriculoperitoneal (VP) shunt require special care
      during pregnancy, although they develop few complications related to
      hydrocephalus. CASE: We recently encountered a pregnant patient with
      hydrocephalus, which was caused by VP shunt malfunction induced by increased
      intra-abdominal pressure associated with pregnancy. She was treated by
      replacement of the VP shunt with a ventriculoatrial (VA) shunt. After treatment,
      she achieved vaginal delivery. CONCLUSION: We recommend VA shunt implantation as
      a treatment option for the management of VP shunt malfunction during pregnancy.
      We further propose that patients in whom the VP shunt is replaced with a VA shunt
      can achieve spontaneous vaginal delivery.

PMID- 20157719
TI  - Diagnosis and management of intra-abdominal, mislocated intrauterine devices.
AB  - PURPOSE: To evaluate the predisposing factors, diagnosis and surgical treatment
      options of patients with intra-abdominal, mislocated intrauterine devices (IUDs).
      METHODS: The diagnosis and management of 18 patients with intra-abdominal,
      mislocated IUDs were analyzed in this retrospective study. RESULTS: Trained
      midwives inserted ten (55%) of the IUDs, while six (33%) were inserted by general
      practitioners and two (11%) by specialist gynecologists. Ten (55.5%) of the
      patients were diagnosed by gynecological examination and ultrasonography (USG);
      abdominal X-ray, in addition, was required in the other eight (44.4%). Eleven
      patients (61%) were managed by laparoscopy, whereas laparotomy was required in
      seven (39%). For all patients, laparoscopy was performed initially. No
      complication was encountered in any of the patients. CONCLUSION: Persons who
      insert IUDs should receive adequate training before certification, because
      inadequate pelvic examination before insertion and inexperience of the inserting
      person might be predisposing factors for uterine perforation. If IUD strings are
      not visible during gynecologic examination, USG should be tried to locate the IUD
      and pelvic X-ray used only when USG fails to locate the IUD. Laparoscopy can be
      the first choice for removal.

PMID- 20157720
TI  - Biodistribution of (137)Cs in a mouse model of chronic contamination by ingestion
      and effects on the hematopoietic system.
AB  - The aim of this work was to define the possible occurrence of hematological
      changes during the course of a chronic ingestion of (137)Cs. A mouse model was
      used, with ingestion through drinking water with a cesium concentration of 20 kBq
      l(-1). Ingestion started in parent animals before mating, and (137)Cs intake and
      its effect on the hematopoietic system was studied in offspring at various ages
      between birth and 20 weeks. (137)Cs content was measured in various organs,
      indicating that (137)Cs was distributed throughout the organism including lympho
      hematopoietic organs, i.e., femurs, spleen and thymus. However, we did not
      observe any effect on the hematopoietic system, whatever the parameter used. In
      fact, blood cell counts, mononuclear cell counts and progenitor frequency in bone
      marrow and spleen, and Flt3-ligand, Erythropoietin, G-CSF and SDF-1 concentration
      in plasma remained unchanged when compared to control animals. Moreover,
      phenotypic analysis did not show any change in the proportions of bone marrow
      cell populations. These results indicate that, although (137)Cs was found in all
      organs implicated in the hematopoietic system, this did not induce any changes in
      bone marrow function.

PMID- 20157721
TI  - Oligoclonal bands and MRI in clinically isolated syndromes: predicting conversion
      time to multiple sclerosis.
AB  - The objective of the study was to evaluate whether the presence of oligoclonal
      bands (OB) adds information in predicting CIS conversion to clinical definite
      multiple sclerosis (CDMS) and conversion time to CDMS. From 1998 to 2006, CIS
      patients were included in a prospective study. Patients underwent brain MRI and
      OB determination within 2 months of the first demyelinating event. We analyzed
      conversion to CDMS and time to conversion to CDMS according to abnormal MRI and
      the presence of OB. Forty patients were included. Fifteen patients (37%)
      converted to CDMS; 14 of them (93.3%) had abnormal baseline MRI (P = 0.01, RR =
      5.9; 95% CI 1.3-10.1) and 13 (86.7%) had positive OB in CSF (P = <0.01, RR = 5.3;
      95% CI 1.6-9.5). The risk of conversion to CDMS in patients with positive OB and
      abnormal baseline MRI was significantly higher compared to patients negative for
      both tests or with only one positive (RR = 9.1; 95% CI 3.5-14.6). Time to
      conversion to CDMS was 6.8 +/- 3.5 months for patients with OB and abnormal
      baseline MRI and 19 +/- 14 months for patients with only one abnormal test. CIS
      patients with abnormal baseline OB in CSF have a higher risk for developing CDMS.
      Regarding conversion time to CDMS, when abnormal MRI was added to positive OB,
      patients converted faster (mean time, 6 vs. 19 months). This information may be
      useful when considering treatment in CIS patients.

PMID- 20157722
TI  - Flexion contractures possibly reflect the existence of hypocortisolism: two case
      reports.
AB  - The diagnosis of adrenal insufficiency is discussed in case of low blood pressure
      and digestive symptoms. Rare inaugural abdomino-crural muscle contracture can be
      a misleading symptom. Here we report two new cases. A 50-year-old woman
      presenting a leaning forward walking attitude and negligence for the past 2
      months was referred to the neurologic unit. Abdomino-crural contracture, clinical
      hypogonadism, and hyponatremia directed towards a panhypopituitarism, which was
      confirmed by subsequent investigations. Pituitary MRI found an empty sella
      turcica. The outcome was dramatic after hormone replacement therapy, with drawing
      up of the trunk and re-establishment of walking after a few days. The second case
      is a 58-year-old man, hospitalized with altered general condition, with a weight
      loss of 22 kg, and anorexia in the aftermath of a comminuted fracture of the
      right lower limb, complicated by pseudoarthrosis. There was amyotrophy on the
      extremities with intense cruralgia. The patient had an antalgic attitude in the
      flexion affecting his rehabilitation. During 1 year, the symptoms were mimicking
      psychiatric disorders, malabsorption, or cancer before the final diagnosis of
      central hypocorticism with normal MRI was established. The evolution was
      remarkable after a few days of therapy with hydrocortisone, where the myalgia
      disappeared, the patient quickly gained weight, and the disappearance of the
      retractions allowed rehabilitation. These two observations emphasize the delayed
      diagnosis of adrenal insufficiency in the case of abdomino-crural-related
      symptoms and the presence of misleading neurological symptoms. The mechanisms of
      this syndrome remain unknown.

PMID- 20157723
TI  - Falls and the falls efficacy scale in Parkinson's disease.
AB  - The purpose of this study was to investigate the relationship between fear of
      falling and fall frequency among patients with idiopathic Parkinson's disease
      (PD). One hundred-two participants with idiopathic PD were interviewed and
      examined. Participants reported the number of falls they had experienced in the
      preceding 3 months. They completed a mini-mental state exam (MMSE) and the falls
      efficacy scale (FES) questionnaire. Disease severity was determined by clinical
      examination using the Hoehn-Yahr staging system. Excluding two outliers who fell
      more than once each day, the subjects fell an average of 1.2 times in a 3 month
      period. There was a positive correlation between the number of falls, freezing of
      gait and Hoehn-Yahr score, and a negative correlation with the MMSE. In a post
      hoc analysis the participants were divided into four groups based on fall
      frequency. The outliers had the lowest FES scores on average, similar to the
      scores seen in the rare fallers group. This study suggests that many factors are
      associated with fear of falling, including fall frequency, disease severity, and
      mental status. In the present study, the patients who fell the most often did not
      report the most fear. The lack of fear of falling but frequent falls in this
      small subgroup may suggest that special techniques to instill suitable caution to
      prevent falls are necessary, or may make training of these patients impossible.

PMID- 20157724
TI  - Identification of previously unreported mutations in CHRNA1, CHRNE and RAPSN
      genes in three unrelated Italian patients with congenital myasthenic syndromes.
AB  - Congenital myasthenic syndromes are rare genetic disorders compromising
      neuromuscular transmission. The defects are mainly mutations in the muscle
      acetylcholine receptor, or associated proteins rapsyn and Dok-7. We analyzed
      three unrelated Italian patients with typical clinical features of congenital
      myasthenic syndrome, who all benefitted from cholinesterase inhibitors. We found
      five mutations: a previously unreported homozygous alphaG378D mutation in the
      CHRNA1 gene, a previously unreported heterozygous epsilonY8X mutation associated
      with a known heterozygous epsilonM292del deletion in the CHRNE gene, and the
      common heterozygous N88K mutation associated with a previously unreported
      heterozygous IVS1 + 2T > G splice site mutation in the RAPSN gene. All three
      patients had two mutant alleles; parents or offspring with a single mutated
      allele were asymptomatic, thus all mutations exerted their effects recessively.
      The previously unreported mutations are likely to reduce the number of AChRs at
      the motor endplate, although the alphaG378D mutation might produce a mild fast
      channel syndrome. The alphaG378D mutation was recessive, but recessive CHRNA1
      mutations have rarely been reported previously, so studies on the effect of this
      mutation at the cellular level would be of interest.

PMID- 20157725
TI  - Network bursts in cortical cultures are best simulated using pacemaker neurons
      and adaptive synapses.
AB  - One of the most specific and exhibited features in the electrical activity of
      dissociated cultured neural networks (NNs) is the phenomenon of synchronized
      bursts, whose profiles vary widely in shape, width and firing rate. On the way to
      understanding the organization and behavior of biological NNs, we reproduced
      those features with random connectivity network models with 5,000 neurons. While
      the common approach to induce bursting behavior in neuronal network models is
      noise injection, there is experimental evidence suggesting the existence of
      pacemaker-like neurons. In our simulations noise did evoke bursts, but with an
      unrealistically gentle rising slope. We show that a small subset of 'pacemaker'
      neurons can trigger bursts with a more realistic profile. We found that adding
      pacemaker-like neurons as well as adaptive synapses yield burst features (shape,
      width, and height of the main phase) in the same ranges as obtained
      experimentally. Finally, we demonstrate how changes in network connectivity,
      transmission delays, and excitatory fraction influence network burst features
      quantitatively.

PMID- 20157726
TI  - Effect of protein modification by malondialdehyde on the interaction between the
      oxygen-evolving complex 33 kDa protein and photosystem II core proteins.
AB  - Previously we observed that the oxygen-evolving complex 33 kDa protein (OEC33)
      which stabilizes the Mn cluster in photosystem II (PSII), was modified with
      malondialdehyde (MDA), an end-product of peroxidized polyunsaturated fatty acids,
      and the modification increased in heat-stressed plants (Yamauchi et al. 2008). In
      this study, we examined whether the modification of OEC33 with MDA affects its
      binding to the PSII complex and causes inactivation of the oxygen-evolving
      complex. Purified OEC33 and PSII membranes that had been removed of extrinsic
      proteins of the oxygen-evolving complex (PSIIOEE) of spinach (Spinacia oleracea)
      were separately treated with MDA. The binding was diminished when both OEC33 and
      PSIIOEE were modified, but when only OEC33 or PSIIOEE was treated, the binding
      was not impaired. In the experiment using thylakoid membranes, release of OEC33
      from PSII and corresponding loss of oxygen-evolving activity were observed when
      thylakoid membranes were treated with MDA at 40 degrees C but not at 25 degrees
      C. In spinach leaves treated at 40 degrees C under light, maximal efficiency of
      PSII photochemistry (F(v)/F(m) ratio of chlorophyll fluorescence) and oxygen
      evolving activity decreased. Simultaneously, MDA contents in heat-stressed leaves
      increased, and OEC33 and PSII core proteins including 47 and 43 kDa chlorophyll
      binding proteins were modified with MDA. In contrast, these changes were to a
      lesser extent at 40 degrees C in the dark. These results suggest that MDA
      modification of PSII proteins causes release of OEC33 from PSII and it is
      promoted in heat and oxidative conditions.

PMID- 20157727
TI  - Epigenetic regulation of peanut allergen gene Ara h 3 in developing embryos.
AB  - Peanut (Arachis hypogaea) allergy is one of the most serious food allergies.
      Peanut seed protein, Ara h 3, is considered to be one of the most important
      peanut allergens. Little is known about the temporal and spatial regulation
      mechanism of Ara h 3 during seed development. In this study, chromatin structure
      of the Ara h 3 promoter was analyzed to examine its transcriptional regulation.
      Analysis of transgenic plants of Arabidopsis thaliana expressing Arah3: GUS
      showed that the Ara h 3 promoter could efficiently direct the seed-specific
      expression of the GUS reporter gene. Chromatin immunoprecipitation revealed that
      nucleosomes were depleted at the core promoter of the Ara h 3 upon full
      activation in the late stage of embryo maturation, which was accompanied by a
      dramatic decrease of histone acetylation. However, in the early stage of embryo
      maturation, histone H3 hyperacetylation at the core promoter of Ara h 3 was
      detected. A decrease of histone H3-K9 dimethylation levels at core promoter of
      Ara h 3 was also observed with concomitant repression of Ara h 3 in the
      vegetative tissues. Our results suggest that the histone modification status of
      Ara h 3 undergoes targeted changes including the increase of histone H3
      acetylation and decrease of histone H3-K9 dimethylation in early maturation
      embryos. In addition, the loss of histone H3 from the proximal promoter of Ara h
      3 is associated with its high expression during late embryo maturation.

PMID- 20157728
TI  - Isolation and functional characterization of a floral tissue-specific R2R3 MYB
      regulator from tobacco.
AB  - Tobacco is a commonly used heterologous system for studying combinatorial
      regulation of the flavonoid biosynthetic pathway by the bHLH-MYB transcription
      factor (TF) complex in plants. However, little is known about the endogenous
      tobacco bHLH and MYB TFs involved in the pathway. Ectopic expression in tobacco
      of heterologous bHLH TF genes, such as maize Lc, leads to increased anthocyanin
      production in the reproductive tissues, suggesting the presence of a reproductive
      tissue-specific MYB TF that interacts with the Lc-like bHLH TFs. We isolated a
      gene (NtAn2) encoding a R2R3 MYB TF from developing tobacco flowers. NtAn2 shares
      high sequence homology with other known flavonoid-related MYB TFs and is mostly
      expressed in developing flowers. Constitutive ectopic expression of NtAn2 induces
      whole-plant anthocyanin production in tobacco and Arabidopsis. In transgenic
      tobacco and Arabidopsis expressing NtAn2, both subsets of early and late
      flavonoid pathway genes are up-regulated. Suppression of NtAn2 by RNAi in tobacco
      resulted in a white-flowered phenotype and the inhibition of the late pathway
      genes. Yeast two-hybrid assays demonstrated that NtAn2 can interact with five
      heterologous bHLH TFs known to induce anthocyanin synthesis in other species
      including maize, perilla, snapdragon and Arabidopsis. Bimolecular fluorescent
      complementation using split YFP demonstrated that NtAn2 interacts with Lc in
      tobacco cells and that the complex is localized to nuclei. Transient co
      expression of NtAn2 and Lc or Arabidopsis TT8 in tobacco protoplasts activated
      the promoters of two key flavonoid pathway genes, chalcone synthase and
      dihydroflavonol reductase. These results suggest that NtAn2 is a key gene
      controlling anthocyanin production in reproductive tissues of tobacco.

PMID- 20157729
TI  - Lymphocyte transformation test detects a response to Campylobacter jejuni
      antigens in patients with Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is an immune-mediated polyneuropathy. Campylobacter
      jejuni-associated gastrointestinal infection is identified as a major
      precipitating agent of GBS; however, a standard test to diagnose this infection
      in patients with GBS is lacking. The aim of the present study was to evaluate an
      outer membrane protein (OMP)-based lymphocyte transformation test (LTT) for the
      diagnosis of C. jejuni infection in GBS. Forty patients with GBS, age and gender
      matched 52 healthy controls (HC) and 46 disease controls (DC) were analyzed for
      C. jejuni infection by culture, polymerase chain reaction (PCR) and LTT.
      Lymphocytes at concentration of 1 x 10(6)/well isolated from GBS patients and
      controls were stimulated with 20 microg/ml of C. jejuni OMP, and (3)H-thymidine
      was incorporated to measure cell proliferation. LTT detected significantly higher
      C. jejuni infection compared to culture (77.5 vs. 2.5%; P < 0.05) and PCR (77.5
      vs. 22.5%; P < 0.05). The cutoff value of lymphocyte proliferation by receiver
      operating characteristic (ROC) curve of 2.5 had 77.5% sensitivity and 96.5%
      specificity. Area under ROC curve was 0.92. The mean SI of the cell proliferation
      for GBS cases was significantly higher than the controls (GBS vs. HC; P < 0.001,
      GBS vs. DC; P < 0.001). LTT appears to be a sensitive tool for detecting
      preceding C. jejuni infection in GBS patients with reasonable sensitivity and
      specificity. It is possible that the activated lymphocytes might play role in the
      pathogenesis of neuronal damage in GBS.

PMID- 20157730
TI  - Scimitar syndrome associated with partial anomalous pulmonary venous draining
      into superior vena cava.
AB  - Scimitar syndrome is a rare congenital cardiopulmonary malformation characterized
      by hypoplasia of the right lung and drainage of the right pulmonary veins into
      the vena cava inferior. It may also be associated with cardiac dextroversion and
      anomalies of the tracheobronchial system, cardiovascular system, and diaphragm.
      Some cases are asymptomatic with others diagnosed in early-childhood period with
      pulmonary hypoplasia and other associated malformations. We present here a
      patient whose venous return of the middle and lower lobes of the right lung is
      into the superior vena cava, which is a very unusual finding for this disorder.

PMID- 20157731
TI  - Overexpression of Galectin-1 is negatively correlated with pathologic
      differentiation grade in oral squamous cell carcinoma.
AB  - PURPOSE: To determine the Galectin-1 protein expression in oral squamous cell
      carcinoma (OSCC). METHODS: Comparative proteomic analysis of an in vitro cellular
      carcinogenesis model of OSCC we previously established was performed to identify
      differentially expressed proteins. Galectin-1 was further validated in vitro
      (human immortalized oral epithelia cell line and OSCC lines) and in vivo (tissue
      samples from OSCC patients) by Western blotting and immunohistochemistry,
      respectively. RESULTS: Increased Galectin-1 protein expression was identified in
      the cancerous cell line compared with the immortalized oral epithelial cell line
      in the in vitro cellular carcinogenesis model, and then validated in the OSCC
      lines and cancerous tissues. Galectin-1 protein expression was negatively
      correlated with the tumor pathologic differentiation grades, a higher Galectin-1
      protein expression indicating a poorer pathologic differentiation grade.
      CONCLUSIONS: Galectin-1 protein expression level increases in OSCC, it may serve
      as a candidate marker for pathologic differentiation grade of OSCC.

PMID- 20157732
TI  - The influence of TXNDC5 gene on gastric cancer cell.
AB  - BACKGROUND: TXNDC5 (thioredoxin domain containing 5) is over-expressed in tumors
      of the cervix, uterus, stomach and lung. However, not much is known about the
      functional roles of TXNDC5 gene in gastric adenocarcinoma. In the present study,
      we intend to investigate the effects of TXNDC5 on the growth, proliferation,
      apoptosis, invasion and cell cycle of the gastric cancer cell line MKN45 and
      normal gastric cell line HFE145. METHODS: TXNDC5 cDNA was inserted into a
      constitutive vector pcDNA3.1 followed by transfection into normal gastric cell
      line HFE145 using liposome. Then, stable transfectants were selected and
      appraised. Specific silencing of TXNDC5 gene was achieved using a vector-based
      short interference RNAs (siRNA) system in gastric cancer cell line MKN45. The
      growth and proliferation were analyzed by cell growth curves and colony-forming
      assay, respectively. The apoptosis and cell cycles of these clones were analyzed
      using flow cytometry. The invasion of these cells was analyzed by cell migration
      assay. The TXNDC5 stable expression cell lines (HFE-TXNDC5) and TXNDC5 RNAi cell
      lines (MKN-SR1,2) were detected and compared with their control groups,
      respectively. RESULTS: HFE-TXNDC5 grew faster than HFE145 and HFE-PC(HFE145
      transfected with pcDNA3.1 vector). MKN-SR1 grew slower than MKN45 and MKN-SS1,2
      (MKN45 transfected with scrambled control duplexes). The cell counts of HFE
      TXNDC5 in the fifth, sixth and seventh days were significantly higher than those
      of control groups (P < 0.05). The cell counts of MKN-SR1 in the fifth, sixth and
      seventh days were significantly lower than those of control groups (P < 0.05).
      Cell cycle analysis showed that there were significant differences in proportions
      of G0-G1 and G2-M phase between HFE-TXNDC5, MKN-SR1 cells and their control
      groups, respectively (P < 0.05). The apoptosis rate of HFE-TXNDC5 was
      significantly lower than that of control groups (P < 0.05). The results of colony
      forming assay showed that the colony formation rate of HFE-TXNDC5 was higher than
      those of control groups, otherwise the rate of MKN-SR1 were lower than those of
      their control groups (P < 0.05). The results of cell migration assay showed that
      the migration rate of HFE-TXNDC5 were significantly higher than that of its
      control group. Conversely, the migration rate of MKN-SR1 was significantly lower
      than that of its control group (P < 0.05). CONCLUSION: TXNDC5 can promote the
      growth and proliferation of gastric cells. Silencing of TXNDC5 can restrain the
      growth and proliferation of gastric cancer cells. The gene can enhance the
      capability of invasion of gastric cancer cells. In some respects, TXNDC5 could be
      thought as a tumor-enhancing gene in gastric cancer.

PMID- 20157733
TI  - Clinical significance of pAKT and CD44v6 overexpression with breast cancer.
AB  - PURPOSE: CD44v6 contributes to apoptosis resistance and metastasis via
      upregulated activity of the PI3K/AKT pathway. The purpose of this study was to
      investigate the expression patterns and predictive value of phosphorylated AKT
      (pAKT) and CD44v6 in breast cancer tissues. METHODS: Expression of pAkt and
      CD44v6 protein was detected using immunohistochemistry in breast cancer tissues
      and lymph node tissues in 98 patients. The correlation between the expression of
      pAkt, CD44v6 and other disease-related characteristics was investigated. The
      prognostic value of pAKT and CD44v6 overexpression for overall survival (OS) and
      disease free survival (DFS) was determined. RESULTS: 37 cases (37.8%) were
      observed as positive for pAkt expression, and 38 cases (38.8%) for CD44V6
      overexpression. Staining was positive for pAKT in 20 of 38 (52.6%) CD44v6(+) and
      17 of 60 (28.3%) CD44v6(-) (P = 0.016). A progressively increased trend of CD44v6
      overexpression was observed from node(-) primary breast cancer tissues to node(+)
      primary cancer tissues to node(+) lymph tissues (P = 0.000). In univariate
      analysis lymph node status, pAKT and CD44V6 were significantly associated with a
      decreased OS and DFS. Multivariate analysis revealed that CD44v6 status was
      associated with a reduced OS (P = 0.003), and pAKT and CD44v6 with a shorter DFS
      (P = 0.012 and 0.016, respectively). CONCLUSIONS: Our data suggested that there
      had an intensive relationship between pAKT and CD44v6 expression in breast cancer
      tissues. The overexpression of CD44v6 was an independent prognostic marker for
      predicting OS and DFS of breast cancer patients.

PMID- 20157734
TI  - A tubulointerstitial nephritis antigen gene defect causes childhood-onset chronic
      renal failure.
AB  - Tubulointerstitial nephritis antigen (TIN-ag), which has been localized to the
      renal tubular basement membrane, is a target antigen in some forms of TIN.
      Physiologically, TIN-ag is thought to be important in maintaining the structure
      of renal tubular basement membrane. Here we describe a child with chronic renal
      failure showing a human TIN-ag gene (hTIN-ag) deletion. Immunohistochemical
      examination using an antihuman TIN-ag monoclonal antibody showed attenuation or
      lack of TIN-ag staining along the renal tubular basement membrane, whereas
      nephrocystin staining was normal in renal tubules. Polymerase chain reaction
      detected no amplification band corresponding to hTIN-ag in this patient. Testing
      for a deletion in this gene showed nearly complete deletion. By using array
      comparative genomic hybridization method, large deletion of a gene mapped on
      chromosome 6p11-6p12 was demonstrated, corresponding to the locus where hTIN-ag
      is located. Therefore, an hTIN-ag defect may be a potent cause of end-stage renal
      failure in childhood.

PMID- 20157735
TI  - Impressive renal damage after acute pyelonephritis in a child.
AB  - Urinary tract infection (UTI) is one of the most common bacterial infections in
      children, and its role in the pathogenesis of scarred kidney is debated. We
      report on a 7-year-old child who presented with severe UTI. The early (day 4)
      renal computed tomography (CT) scan showed normal-sized kidneys (110 mm on the
      left, 105 mm on the right), whereas the control CT scan and dimercaptosuccinic
      acid (DMSA) scan, performed 1 and 2 months later, respectively, showed a small
      scarred right kidney (60 mm) with a 12% residual function. An intermittent right
      vesicoureteral reflux (VUR) was diagnosed by direct isotopic cystography and then
      treated by Cohen vesicoureteral reimplantation. The patient remained free of
      infectious recurrence, hypertension, or renal function decrease. This report
      demonstrates that one episode of acute pyelonephritis can lead to severe renal
      scarring. Whereas antenatal lesions are thought to have a stronger role in the
      causal pathway for reflux nephropathy than is UTI in addition to VUR, this
      observation reminds us that UTI can truly play an important role in damaging
      kidneys.

PMID- 20157736
TI  - Outcome of accidental peritoneal dialysis catheter holes or tip exposure.
AB  - Pediatric peritoneal dialysis (PD) patients are at risk for acute peritonitis.
      One risk factor is accidental exposure of the catheter to a non-sterile surface.
      We studied catheter exposures in 17 pediatric patients receiving PD who developed
      16 holes and 12 other accidental exposures. The rate of exposures was 3.7
      events/100 patient-months. After exposure, the mean counts (+ or - standard
      error) of white blood cells (WBC), red blood cells, and neutrophils were 39.8 +
      or - 19.3, 9.5 + or - 7.1, and 24.2 + or - 5.3/mm(3), respectively. There was a
      trend towards higher peritoneal fluid WBC in patients with holes than in those
      with exposures (60.1 + or - 34.8 vs. 15.4 + or - 5.1/mm(3), respectively; p =
      0.2). The initial peritoneal fluid WBC count was significantly higher if there
      was a positive culture than a negative culture (165.0 + or - 132.6 vs. 20.3 + or 
      6.4/mm(3), respectively; p = 0.01). The percentage of neutrophils was higher in
      patients with a positive culture than in those with a negative culture (54.7 + or
      - 14.1 vs. 19.1 + or - 4.9%, respectively; p = 0.01). Of the 28 patients, 27
      received a single dose of intravenous antibiotics, as per the protocol at that
      time. Among those treated, 7% developed a positive culture (all staphylococcal
      species) while 93% had a negative culture. We conclude that following accidental
      exposure of the peritoneal dialysis catheter: (1) the prevalence of peritonitis
      is low; (2) measuring peritoneal fluid WBC provides treatment guidance; (3) if
      treatment is initiated, it should be applied intraperitoneally and include
      activity against Gram-positive organisms.

PMID- 20157737
TI  - DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of
      hemolytic uremic syndrome.
AB  - DEAP-HUS [Deficiency of CFHR (complement factor H-related) plasma proteins and
      Autoantibody Positive form of Hemolytic Uremic Syndrome] represents a novel
      subtype of hemolytic uremic syndrome (HUS) with unique characteristics. It
      affects children and requires special clinical attention in terms of diagnosis
      and therapy. DEAP-HUS and other atypical forms of HUS share common features, such
      as microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia.
      However, DEAP-HUS has the unique combination of an acquired factor in the form of
      autoantibodies to the complement inhibitor Factor H and a genetic factor which,
      in most cases, is the chromosomal deletion of a 84-kbp fragment within human
      chromosome 1 that results in the absence of the CFHR1 and CFHR3 proteins in
      plasma. Special attention is required to diagnose and treat DEAP-HUS patients.
      Most patients show a favorable response to the reduction of autoantibody titers
      by either plasma therapy, steroid treatment, and/or immunosuppression. In
      addition, in those DEAP-HUS patients with end-stage renal disease, the reduction
      of autoantibody titers prior to transplantation is expected to prevent post
      transplant disease recurrence by aiming for full complement control at the
      endothelial cell surface in order to minimize adverse complement and immune
      reactions.

PMID- 20157738
TI  - Normal-range albuminuria does not exclude nephropathy in diabetic children.
AB  - Clinically detectable diabetic nephropathy (DN) begins with the development of
      microalbuminuria (MA). However, early renal dysfunction may be overlooked despite
      using that method. On the other hand, the gold standard in DN detection-that is,
      renal biopsy-is highly invasive. The aim of this study was to evaluate the level
      of neutrophil-gelatinase-associated lipocalin (NGAL) and interleukin (IL)-18 and
      their relations to albumin excretion rate (AER) in children with normal-range
      albuminuria, e.g. in those considered as not presenting diabetic nephropathy. The
      study group consisted of 22 children (age 12.7 +/- 3.5 years) with type 1
      diabetes mellitus (T1DM). Long-term glycemic control was assessed on hemoglobin
      A1c (HbA1c) levels (8.52 +/- 1.78%). All patients presented normal estimated
      glomerular filtration rate (eGFR) (141 +/- 23 ml/min/1.73 m(2)) and normal
      urinary albumin excretion (13.09 +/- 7.63 mg/24 h). Fourteen healthy children
      served as a control group. Children with T1DM showed increased NGAL values with
      respect to controls-interestingly, both in serum (sNGAL) (867.43 +/- 341.98 vs.
      655.29 +/- 196.17 ng/ml; p = 0.04) and in urine (uNGAL) (420.04 +/- 374.16 vs.
      156.53 +/- 185.18 ng/ml, p = 0.04). IL-18 levels were not different in both
      groups both in serum (58.52 +/- 20.11 vs. 69.79 +/- 58.76 ng/ml; NS) and in urine
      (14.53 +/- 12.74 vs. 14.60 +/- 10.92 ng/ml; NS). Despite the relatively small
      study group, the positive correlation between sNGAL and AER was found [AER (mg/24
      h) = 3.1893 + 0.01141 x sNGAL (ng/ml); r = 0.51; p = 0.014] as well as between
      uNGAL and AER [AER (mg/24 h) = 8.7538 + 0.01032 x uNGAL (ng/ml); r = 0.51; p =
      0.016]. No relationship between sNGAL and uNGAL, and GFR and HbA1c were found.
      Normal-range albuminuria does not exclude diabetic nephropathy defined as
      increased sNGAL and uNGAL concentration. NGAL measurement can be more sensitive
      than MA and may become a useful tool for evaluating renal involvement in diabetic
      children.

PMID- 20157739
TI  - Levels of urinary transforming growth factor beta-1 in children with D+ hemolytic
      uremic syndrome.
AB  - About 25-50% of survivors of the acute phase of postdiarrheal hemolytic uremic
      syndrome (D+ HUS) develop chronic renal disease. Transforming growth factor beta
      1 (TGFbeta-1) is the main fibrogenic growth factor in humans, and there is a
      significant correlation between its levels and the grade of interstitial fibrosis
      in chronic nephropathies. We hypothesized that increased urinary TGFbeta-1 may be
      an early indicator of sequelae in D+ HUS patients who show no sign of renal
      damage as determined by conventional diagnostic tests. We therefore compared the
      levels of TGFbeta-1 in urine collected from healthy controls (HC) (n = 18) with
      that from patients with a past history of D+ HUS (n = 39). We found that TGFbeta
      1 excretion was significantly higher (p < 0.001) in the patient group (median
      level 73 pg/mg creatinine) than in the HC (median level 28 pg/mg creatinine).
      TGFbeta-1 excretion did not correlate with age, white blood cell count, length of
      oligoanuric period, maximum creatinine at the acute stage, or length of the
      follow-up. Since TGFbeta-1 excretion may reflect ongoing renal tissue damage, our
      results emphasize the need for the lifelong follow-up of patients with a past
      history of D+ HUS, even those showing apparent recovery. Long-term monitoring of
      this cohort is necessary to determine the clinical utility of our findings.

PMID- 20157740
TI  - Beneficial effects of footbaths in controlling spasticity after stroke.
AB  - Footbaths are considered to provide beneficial thermal therapy for post-stroke
      patients with spasticity, but their anti-spastic effects have not been
      investigated comprehensively. The present study aimed to evaluate alterations in
      motor-neuron excitability using F-wave parameters in post-stroke patients with
      spastic hemiplegia. Subjects' legs below the knee joint were immersed in water at
      41 degrees C and F-wave recordings were made over the abductor hallucis muscle
      before, immediately after, and 30 min after thermal treatment. Antidromic
      stimulation was performed on the tibial nerve at the ankle. Measurements included
      F-wave amplitude, F-wave/M-response ratio, changes in modified Ashworth scale
      (MAS), body temperature and surface-skin temperature. The mean values of both F
      wave parameters were higher on the affected side before footbath treatment. In
      post-stroke patients, the mean values of F-wave parameters were significantly
      reduced after footbath treatment (P < 0.01). The anti-spastic effects of footbath
      treatment were indicated by decreased F-wave parameters, in parallel with
      decreases in MAS. Body temperature was significantly increased both immediately
      after, and 30 min following footbath treatment in both groups, which appeared to
      play an important role in decreased spasticity. Surface-skin temperature
      increased immediately after footbath treatment in both groups and returned to
      baseline 30 min later. These findings demonstrate that the use of footbaths is an
      effective nonpharmacological anti-spastic treatment that might facilitate stroke
      rehabilitation.

PMID- 20157741
TI  - One-stage posterior instrumentation surgery for the treatment of osteoporotic
      vertebral collapse with neurological deficits.
AB  - The number of reports describing osteoporotic vertebral fracture has increased as
      the number of elderly people has grown. Anterior decompression and fusion alone
      for the treatment of vertebral collapse is not easy for patients with comorbid
      medical problems and severe bone fragility. The purpose of the present study was
      to evaluate the efficacy of one-stage posterior instrumentation surgery for the
      treatment of osteoporotic vertebral collapse with neurological deficits. A
      consecutive series of 21 patients who sustained osteoporotic vertebral collapse
      with neurological deficits were managed with posterior decompression and short
      segmental pedicle screw instrumentation augmented with ultra-high molecular
      weight polyethylene (UHMWP) cables with or without vertebroplasty using calcium
      phosphate cement. The mean follow-up was 42 months. All patients showed
      neurologic recovery. Segmental kyphotic angle at the instrumented level was
      significantly improved from an average preoperative kyphosis of 22.8-14.7 at a
      final follow-up. Spinal canal occupation was significantly reduced from an
      average before surgery of 40.4-19.1% at the final follow-up. Two patients
      experienced loosening of pedicle screws and three patients developed subsequent
      vertebral compression fractures within adjacent segments. However, these patients
      were effectively treated in a conservative fashion without any additional
      surgery. Our results indicated that one-stage posterior instrumentation surgery
      augmented with UHMWP cables could provide significant neurological improvement in
      the treatment of osteoporotic vertebral collapse.

PMID- 20157742
TI  - Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a
      model for Down's syndrome.
AB  - Down's syndrome (DS), with an incidence of one in 800 live births, is the most
      common genetic disorder associated with mental retardation. This trisomy on
      chromosome 21 induces a variable phenotype in which the only common feature is
      the presence of mental retardation. The neural mechanisms underlying mental
      retardation might include defects in the formation of neuronal networks and
      neural plasticity. DS patients have alterations in the morphology, the density
      and the distribution of dendritic spines in the pyramidal neurons of the cortex.
      Our hypothesis is that the deficits in dendritic arborization observed in the
      principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most
      of the structural alterations observed in humans) may be mediated to some extent
      by changes in their inhibitory inputs. Different types of interneurons control
      different types of inhibition. Therefore, to understand well the changes in
      inhibition in DS, it is necessary to study the different types of interneurons
      separately. We have studied the expression of synaptophysin, Glutamic acid
      decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the
      primary somatosensory cortex of 4-5 month old Ts65Dn mice. We have observed an
      increment of GAD67 immunoreactivity that is related mainly to an increment of
      calretinin-immunoreactive cells and among them the ones with bipolar morphology.
      Since there is a propensity for epilepsy in DS patients, this increase in
      interneurons might reflect an attempt by the system to block overexcitation
      rather than an increment in total inhibition and could explain the deficit in
      interneurons and principal cells observed in elderly DS patients.

PMID- 20157743
TI  - Preliminary fMRI findings on the effects of event rate in adults with ADHD.
AB  - Inhibition problems in attention deficit hyperactivity disorder (ADHD) are
      sensitive to stimulus event rate. This pilot study explores the neural basis of
      this increased susceptibility to event rate in ADHD. Event-related functional
      magnetic resonance imaging was used in conjunction with the administration of a
      fast (1.5 s) and a slow (7 s) Go/No-Go task. Brain activity patterns and reaction
      times of ten young male adults with ADHD (two of whom were in partial remission)
      and ten healthy male controls were compared. The ADHD group responded slower than
      controls with greater variability but with similar number of errors. Accurate
      response inhibition in the ADHD group in the slow condition was associated with
      widespread fronto-striatal activation, including the thalamus. For correct Go
      trials only, the ADHD group compared with controls showed substantial under
      activation in the slow condition. The observed abnormal brain activation in the
      slow condition in adults with ADHD supports a fronto-striatal etiology, and
      underlines a presumed activation regulation deficit. Larger sample sizes to
      further validate these preliminary findings are needed.

PMID- 20157744
TI  - Maternal personality disorder and babies' exposure to tobacco smoke.
AB  - This study examined the association between smoking practices and maternal
      personality disorder in a sample of 200 mothers of 2-month-old babies. Maternal
      personality disorder was robustly associated with allowing smoking in the home
      and also exposing the baby to tobacco smoke. The findings suggest that mothers
      with personality disorders might particularly benefit from targeting with
      education and advice about reducing their baby's exposure to environmental
      tobacco smoke in the postpartum period.

PMID- 20157745
TI  - Analgesic effect of raloxifene on back and knee pain in postmenopausal women with
      osteoporosis and/or osteoarthritis.
AB  - To assess the effect of raloxifene on bone and joint pain, 24 postmenopausal
      women with back or knee pain or both were randomly divided into two groups, based
      on the chronological sequence of consultation, to be treated with 60 mg
      raloxifene and 1 microg alfacalcidol (RA)/day (group RA) or 1 microg alfacalcidol
      alone (A)/day (group A), respectively, for 6 months. Pain following knee loading
      (KL) by standing up from a chair and bending the knee by squatting, knee and
      spine loading (KSL) by walking horizontally and ascending and descending stairs,
      and spine loading (SL) by lying down supine on a bed and leaving the bed to stand
      was evaluated by electroalgometry (EAM), based on measurement of the fall of skin
      impedance, and a visual rating scale (VRS), recording subjective pain on a scale
      of 0-100 between no pain and unbearable pain. The two groups showed no
      significant difference as to age, indices of mineral metabolism, back and knee
      pain, and bone status. RA gave a significantly greater analgesic effect than A by
      both EAM (P = 0.0158) and VRS (P = 0.0268) on overall comparison of the mean
      response to all modalities of exercise loading. Paired comparison between
      pretreatment and posttreatment indicated a significant effect of RA by both EAM
      (P = 0.0045) and VRS (P = 0.0017), but not that of A. The analgesic effect was
      more clearly noted on combined knee-spine loading (KSL) and spine loading (SL)
      than simple knee loading (KL). Monthly comparison of the analgesic effect
      indicated a significantly better analgesic effect in the fifth month by VRS. RA
      effect greater than A was more evident by EAM than VRS and during months 3-6 than
      during 1-2 months, suggesting a slowly progressive effect of RA. Pain evaluation
      by EAM and VRS mostly gave parallel results, except for a few occasions such as
      knee loading and spine loading by sitting up and leaving a bed, when EAM detected
      a positive effect but VRS failed to do so. RA appeared to be more effective on
      bone and joint pain than A in postmenopausal women according to both EAM and VRS
      measurements.

PMID- 20157747
TI  - Australian palliative care providers' perceptions and experiences of the barriers
      and facilitators to palliative care provision.
AB  - OBJECTIVE: People with advanced cancer who may benefit from specialised
      palliative care (SPC) do not necessarily access such services. METHODS: To obtain
      a deeper understanding of issues affecting access to SPC, five focus groups were
      undertaken with nurses (35), physicians (three), allied health professionals
      (seven) and an academic involved in providing care. RESULTS: Thematic analysis
      revealed that palliative care providers consistently view palliative care as a
      broad holistic approach to care benchmarked on good symptom management. Whilst
      participants themselves perceived SPC as aiming to maximise the quality of life
      of the patient and family across all domains of care, they perceived that some
      health professionals and community members viewed palliative care largely as
      symptom control and terminal care for access after all disease-modifying
      treatment has been exhausted. Concern was expressed that such misconceptions were
      an important barrier to timely SPC. Participants did not nominate a time or
      particular milestone in the disease process which should prompt referral and
      suggested that SPC be available at any time where needs are complex and/or are
      not being met. CONCLUSION: Failure to properly recognise and understand the
      breadth of care provided within the palliative care framework may result in
      people with advanced cancer and their caregivers not accessing SPC services or
      accessing them too late to receive maximum benefit. Education may be required to
      promote the holistic nature of SPC services amongst health professionals and the
      community and to help realise the potential benefits to patients, families and
      health professionals resulting from timely access to SPC services.

PMID- 20157746
TI  - An evaluation of the factors that affect the health-related quality of life of
      children following myelosuppressive chemotherapy.
AB  - PURPOSE: The purposes of this study, in children who were assessed 1 week after
      the administration of myelosuppressive chemotherapy were: to compare the total
      and subscale scores on a generic measure of health-related quality of life
      (HRQOL) to normative data from healthy children and describe the relationships
      between demographic, clinical, and symptom characteristics of children with
      cancer and generic and disease-specific dimensions of HRQOL. METHODS: Patients (n
      = 61) were predominantly male (52.5%), minority (63.9%), and 14.7 years of age.
      Children completed the Memorial Symptom Assessment Scale for 10- to 18-year olds,
      the PedsQLTM Generic and Cancer Modules, and the Karnofsky Performance Status
      (KPS) scale 1 week after the start of a chemotherapy cycle. RESULTS: The mean
      number of symptoms per patient was 10.6. Compared with the normative sample,
      children with cancer reported significantly lower scores for the total scale and
      all of the subscales except emotional and social functioning. No significant
      differences were found between any demographic characteristics and total or
      subscale scores on the generic or disease-specific measures of HRQOL. Lower KPS
      scores were associated with poorer generic and disease-specific HRQOL scores. In
      addition, a higher number of symptoms was associated with poorer generic and
      disease-specific HRQOL scores. Finally, higher symptom distress scores were
      associated with poorer generic and disease-specific HRQOL scores. CONCLUSION:
      Among the demographic, clinical, and symptom characteristics studied, poorer
      functional status and higher symptom burden were associated with significant
      decreases in HRQOL in children who received myelosuppressive chemotherapy.

PMID- 20157748
TI  - Diagnostic accuracy of immunochemical versus guaiac faecal occult blood tests for
      colorectal cancer screening.
AB  - BACKGROUND: Immunochemical tests show important advantages over chemical-based
      faecal occult blood tests (FOBT) for colorectal cancer (CRC) screening, but
      comparison studies are limited. This study was performed to compare the accuracy
      of a sensitive immunochemical test with the guaiac test for detecting significant
      neoplasia (advanced adenomas and CRC) in an average-risk population. METHODS: A
      random sample of 2288 asymptomatic subjects 50-79 years of age was prospectively
      included. Participants received three cards of the guaiac test, one sample of a
      latex-agglutination test (haemoglobin cut-off 50 ng/ml), and an invitation to
      undergo colonoscopy. Test sensitivity, specificity, and positive and negative
      predictive values (PPV and NPV) were calculated in 1756 compliers. RESULTS:
      Immunochemical and guaiac tests were positive in 143 (8.1%) and 62 (3.5%)
      subjects, respectively. Complete colonoscopy, performed in 402 participants (158
      FOBT+ and 244 FOBT-), detected 14 (0.8%) patients with CRC and 49 (2.8%) with
      advanced adenomas. The immunochemical and guaiac tests for significant colorectal
      neoplasia showed sensitivities of 61% versus 23.8%, specificities of 95.1% versus
      97.7%, PPVs of 43.4% versus 39.0%, and NPVs of 97.5% versus 95.4%, respectively.
      Proximal significant neoplasms were more frequently detected with the
      immunochemical test (85% vs. 15%) The relative risk for detecting significant
      neoplasia was superior in patients with a positive immunochemical test (RR 16.93;
      CI 7.94-36.10) than with a positive guaiac test (RR 3.34; CI 2.17-5.15).
      CONCLUSION: A sensitive immunochemical test is markedly superior to the guaiac
      test for detecting significant colorectal neoplasia, and should be considered the
      first-choice FOBT for CRC screening in the average-risk population.

PMID- 20157749
TI  - K-ras mutation in the major duodenal papilla and gastric and colonic mucosa in
      patients with autoimmune pancreatitis.
AB  - BACKGROUND: Pancreatic cancer occurs in some patients with autoimmune
      pancreatitis (AIP). Significant K-ras mutations are frequently detected in the
      pancreas of AIP patients. AIP may be a pancreatic lesion of IgG4-related systemic
      disease. Gastric and colonic cancer can occur during the follow up of AIP
      patients. We examined K-ras mutations in the major duodenal papilla and gastric
      and colonic mucosa of AIP patients. METHODS: K-ras analysis and/or
      immunohistochemical study was performed on the tissues of the major duodenal
      papilla (n = 8), gastric mucosa (n = 5), colonic mucosa (n = 3), pancreas (n =
      5), common bile duct (n = 5), and gallbladder (n = 4) of 12 AIP patients.
      RESULTS: Significant K-ras mutations were detected in the major duodenal papilla
      of 4 of 8 cases [GAT (n = 4)], in the gastric mucosa of 2 of 4 cases [AGT (n =
      2)], and in the colonic mucosa of 2 of 3 cases [GAT (n = 2)]. Significant K-ras
      mutations were detected in the pancreas of all 5 cases [GAT (n = 5), in the
      common bile duct of 4 cases (GAT (n = 2), TGT (n = 1), and GCT/TGT (n = 1)], and
      in the gallbladder epithelium of 3 cases [GAT (n = 1), GCT (n = 1), and GTT (n =
      1)]. K-ras mutations were detected in the organs associated with IgG4-related
      fibroinflammation with abundant infiltration of T lymphocytes and forkhead box P3
      positive cells. CONCLUSIONS: Significant K-ras mutations were frequently detected
      in the major duodenal papilla and gastric and colonic mucosa of AIP patients. AIP
      patients may have risk factors for gastric and colonic cancer, but the mechanisms
      of K-ras mutation and its clinical implications are not clear.

PMID- 20157750
TI  - Isolation of hydrocarbon-degrading extremely halophilic archaea from an
      uncontaminated hypersaline pond (Camargue, France).
AB  - Little information exists about the ability of halophilic archaea present in
      hypersaline environments to degrade hydrocarbons. In order to identify the
      potential actors of hydrocarbon degradation in these environments, enrichment
      cultures were prepared using samples collected from a shallow crystallizer pond
      with no known contamination history in Camargue, France, with n-alkanes provided
      as source of carbon and energy. Five alkane-degrading halophilic archaeal strains
      were isolated: one (strain MSNC 2) was closely related to Haloarcula and three
      (strains MSNC 4, MSNC 14, and MSNC 16) to Haloferax. Biodegradation assays showed
      that depending on the strain, 32 to 95% (0.5 g/l) of heptadecane was degraded
      after 30 days of incubation at 40 degrees C in 225 g/l NaCl artificial medium.
      One of the strains (MSNC 14) was also able to degrade phenanthrene. This work
      clearly shows for the first time the potential role of halophilic archaea
      belonging to the genera Haloarcula and Haloferax in the degradation of
      hydrocarbons in both pristine and hydrocarbon-contaminated hypersaline
      environments.

PMID- 20157751
TI  - Theoretical investigation of the ring opening process of verdoheme to biliverdin
      in the presence of dioxygen.
AB  - The conversion of ferrous verdoheme to ferric biliverdin in the presence of O(2)
      was investigated using the B3LYP method. Both 6-31G and 6-31G (d) basis sets were
      employed for geometry optimization calculation as well as energy stabilization
      estimation. Three possible pathways for the conversion of iron verdoheme to iron
      biliverdin were considered. In the first route oxygen and reducing electron were
      employed. In this path formation of ferrous verdoheme-O(2) complex was followed
      by the addition of one electron to the ferrous-oxycomplex to produce ferric
      peroxide intermediate. The ferric peroxide intermediate experienced an
      intramolecular nucleophilic attack to the most positive position at 5-oxo carbons
      on the ring to form a closed ring biliverdin. Subsequently the ring opening
      process took place and the iron (III) biliverdin complex was formed. Closed ring
      iron biliverdin intermediate and open ring iron biliverdin formed as a product of
      verdoheme cleavage were respectively 13.20 and 32.70 kcal mol(-1) more stable
      than ferric peroxide intermediate. Barrier energy for conversion of ferric
      peroxide to closed ring Fe (III) biliverdin and from the latter to Fe (III)
      biliverdin were respectively 8.67 and 3.35 kcal mol(-1). In this path spin ground
      states are doublet except for iron (III) biliverdin in which spin state is
      quartet. In the second path a ferrous-O(2) complex was formed and, without going
      to a one electron reduction process, nucleophilic attack of iron superoxide
      complex took place followed by the formation of iron (III) biliverdin. This path
      is thermodynamically and kinetically less favorable than the first one. In
      addition, iron hydro peroxy complex or direct attack of O(2) to macrocycle to
      form an isoporphyrin type intermediate have shown energy surfaces less favorable
      than aforementioned routes.

PMID- 20157753
TI  - Comparing the reliability of a new fluorescence camera with conventional laser
      fluorescence devices in detecting caries lesions in occlusal and smooth surfaces
      of primary teeth.
AB  - The aims of this in vitro study were (1) to compare the reliability of a new
      fluorescence camera (FC; VistaProof) with that of two other laser fluorescence
      devices (DIAGNOdent and DIAGNOdent pen) in assessing smooth and occlusal caries
      lesions in primary teeth and (2) to determine the influence of the spacer, the
      protective cover and air drying on the FC readings. We selected 129 primary
      molars which were divided into two groups: smooth surfaces (n=68) and occlusal
      surfaces (n=61). Two trained examiners performed the evaluations using the FC and
      the other laser fluorescence devices separately. One examiner repeated all
      assessments after 1 week. Inter- and intraexaminer reproducibility was calculated
      from the absolute values derived from the devices using intraclass correlation
      coefficient (ICC) and Bland-Altman analysis. Pearson correlation was performed
      among the values obtained with the different devices. For aim 2, only teeth from
      the occlusal surface group were used. Another examiner performed measurements
      with the FC, varying the size of the spacer, the use of the plastic protective
      cover and the drying time (0, 3 and 15 s). Wilcoxon's test was used to compare
      these measurements. High values of interexaminer ICC were observed with the FC in
      both experiments. However, the highest intraexaminer ICC for smooth surfaces was
      found for the DIAGNOdent (ICC 0.918). A positive correlation between all methods
      was observed in both studies. Only drying for 15 s significantly increased the FC
      readings. In conclusion, the FC showed high reliability for occlusal and smooth
      surfaces, similar to the other fluorescence methods tested. Additionally,
      prolonged air drying increased the FC measurements.

PMID- 20157752
TI  - The cag PAI is intact and functional but HP0521 varies significantly in
      Helicobacter pylori isolates from Malaysia and Singapore.
AB  - Helicobacter pylori-related disease is at least partially attributable to the
      genotype of the infecting strain, particularly the presence of specific virulence
      factors. We investigated the prevalence of a novel combination of H. pylori
      virulence factors, including the cag pathogenicity island (PAI), and their
      association with severe disease in isolates from the three major ethnicities in
      Malaysia and Singapore, and evaluated whether the cag PAI was intact and
      functional in vitro. Polymerase chain reaction (PCR) was used to detect dupA,
      cagA, cagE, cagT, cagL and babA, and to type vacA, the EPIYA motifs, HP0521
      alleles and oipA ON status in 159 H. pylori clinical isolates. Twenty-two strains
      were investigated for IL-8 induction and CagA translocation in vitro. The
      prevalence of cagA, cagE, cagL, cagT, babA, oipA ON and vacA s1 and i1 was >85%,
      irrespective of the disease state or ethnicity. The prevalence of dupA and the
      predominant HP0521 allele and EPIYA motif varied significantly with ethnicity (p
      < 0.05). A high prevalence of an intact cag PAI was found in all ethnic groups;
      however, no association was observed between any virulence factor and disease
      state. The novel association between the HP0521 alleles, EPIYA motifs and host
      ethnicity indicates that further studies to determine the function of this gene
      are important.

PMID- 20157754
TI  - Decrease in incidence of surgical site infections in contemporary series of
      patients with radical cystectomy.
AB  - We previously reported that the incidence of surgical site infection (SSI) after
      radical cystectomy was 33% between January 1996 and December 2003 at Sapporo
      Medical University Hospital. Base on that result, we modified perioperative
      management for surgical wounds after January 2004. The modifications included the
      method of suturing and standardization of the period for removal of closed drains
      and surgical dressings. This study compared the incidence of SSI between the
      former and latter periods, and assessed risk factors for SSI. The study consisted
      of 109 patients between January 1996 and December 2003 (Group A), and 104
      patients between January 2004 and December 2007 (Group B), who underwent radical
      cystectomy and urinary diversion or reconstruction. The incidence of SSI was
      reduced from 32.1% in Group A to 18.2% in Group B (p = 0.027). Methicillin
      resistant Staphylococcus aureus (MRSA) was isolated from SSI wounds in 40.0% of
      patients in Group A and 42.1% of those in Group B. Preoperative MRSA bacteriuria
      was the only risk factor for SSI in both groups. The incidences of SSI in
      patients who had such bacteriuria were 45.4% in Group A and 50.0% in Group B.
      Modification of perioperative management for the surgical wound was partly
      responsible for the reduction of the incidence of SSI. In conclusion, MRSA is
      still the main isolated pathogen of SSI after radical cystectomy and this
      clinical problem remains a challenge to urologists. Effective countermeasures are
      needed for MRSA bacteriuria involved in the development of SSI.

PMID- 20157755
TI  - Fatal cytomegalovirus infection with CD4+ T-lymphocytopenia during corticosteroid
      therapy for bronchial asthma.
AB  - An 80-year-old woman was admitted with dyspnea. She had been treated with oral
      prednisolone for bronchial asthma. She was intravenously treated with
      dexamethasone. On the 9th day, she presented oliguria and thrombocytopenia. She
      was diagnosed as dehydration and disseminated intravascular coagulation, and was
      treated with hydration and heparin infusion. On the 12th day, she presented
      macroscopic hematuria and melena. Cystoscopy revealed hemorrhagic cystitis. Bone
      marrow aspiration showed hemophagocytosis. Serum antigen of cytomegalovirus (CMV)
      was positive. CD4+ T cell count was very low (40/microL). She was diagnosed as
      disseminated CMV infection, and was treated with gancyclovir and immunoglobulin
      infusion. On the 14th day, she died of pneumonia. This is the first report of
      fatal CMV infection during corticosteroid therapy for bronchial asthma.

PMID- 20157756
TI  - Carbon dioxide exchange in a cool-temperate evergreen coniferous forest over
      complex topography in Japan during two years with contrasting climates.
AB  - We investigated carbon dioxide (CO(2)) exchange and its environmental response
      during two years with contrasting climate (2006 and 2007) in a cool-temperate
      mixed evergreen coniferous forest dominated by Japanese cedar (Cryptomeria
      japonica) and Japanese cypress (Chamaecyparis obtusa). The study, which was
      conducted in a mountainous region of central Japan, used the eddy-covariance
      technique. Our results (crosschecked using the common u (*) approach and van
      Gorsel's alternative approach) showed that annual gross primary production (GPP)
      and ecosystem respiration (RE) were at least 6% higher in the dry year than in
      the wet year, whereas net ecosystem exchange (NEE) was similar in both years.
      Without soil water stress, strong light stress or seasonality of plant area index
      during most of the study period, the forest had high metabolic activity. GPP and
      RE differed greatly between the two years, especially in spring (April-May) and
      summer (July-September), respectively. The spring GPP difference (>20%) was
      influenced by different winter air temperatures and snow melt timing, which
      controlled photosynthetic capacity in spring, and by different spring light
      intensities. The annual NEE differed depending on the evaluation method used, but
      the mean 2-year NEE estimated by the u (*) threshold approach [-3.39 +/- 0.11
      (SD) MgC ha(-1) year(-1)] appears more reasonable in comparison with results from
      other forests.

PMID- 20157757
TI  - Establishment of the evergreen broad-leaved tree species Castanopsis cuspidata in
      an abandoned secondary forest in western Japan.
AB  - Recently, populations of Castanopsis cuspidata have often expanded into secondary
      forests in western Japan. To determine the establishment processes of this
      species, we analyzed its spatial distribution in a secondary forest dominated by
      Quercus variabilis and Quercus serrata that is located adjacent to a stand
      dominated by C. cuspidata. Saplings, defined as >or=30 cm stem length (SL) and <5
      cm diameter at breast height (DBH), were abundant and their size distribution was
      inversely J-shaped, indicating continuous recruitment. Although seedlings (SL <
      30 cm) and small saplings (30 <or= SL < 50 cm) of C. cuspidata were aggregated
      near flowering trees of this species, some were found >or=40 m from the nearest
      adults, suggesting that there is animal-aided dispersal of acorns. The
      distribution of larger-sized individuals (>or=100 cm SL) of C. cuspidata was
      unrelated to distance from the nearest flowering C. cuspidata or dominant Quercus
      species (>or=5 cm DBH), but was associated with dead Pinus densiflora trees,
      which were abundant at the site. Thus, the establishment of C. cuspidata in this
      forest is controlled mainly by two factors, viz. patterns of acorn dispersal by
      animals, and forest disturbance regime (i.e., deaths of pine trees).

PMID- 20157759
TI  - Climate changes health.

PMID- 20157758
TI  - The epidemiological profile of alcohol and other drug use in metropolitan China.
AB  - PURPOSE: There is evidence that alcohol, tobacco, and other drug use may be
      rising in China, but epidemiological studies that examine several drugs
      simultaneously and the transition from initial try to current use are limited.
      The present study provides an epidemiological profile of drug use in contemporary
      metropolitan China. METHODS: A multistage probability sampling method was used to
      select household-dwelling adults in Beijing and Shanghai. Standard face-to-face
      interviews with 5,201 participants were completed during 2002-2003. RESULTS: An
      estimated 70-76% had used any type of drug: alcohol and tobacco were the most
      commonly used drugs (alcohol, 67%; tobacco, 39%). Regarding extra-medical use of
      internationally regulated drugs, sedatives and analgesics were most common and
      illegal drug use was rare. The majority of tobacco users used it recently
      (82.5%), especially young adults. Male-female differences were observed in
      lifetime tobacco use, but not for recent use. Concurrent use of alcohol and
      tobacco was very common. CONCLUSION: Psychoactive drug use is common in
      metropolitan China. Public health policies and prevention initiatives may be
      needed to address associated problems that may increase following the country's
      rapid socioeconomic change.

PMID- 20157760
TI  - Interleukin-23 receptor genetic polymorphisms and Crohn's disease susceptibility:
      a meta-analysis.
AB  - OBJECTIVE: This study was designed to evaluate whether interleukin-23 receptor
      (IL-23R) polymorphisms were associated with Crohn's disease (CD) susceptibility.
      METHODS: PubMed, MEDLINE, and Embase were searched for studies that investigated
      the IL-23R variants and CD risk. Meta-analysis from all eligible case-control
      studies was performed to assess the purported associations. RESULTS: Our analysis
      found that variant minor alleles for single nucleotide polymorphisms (SNPs)
      rs11209026 (Arg381Gln) (P < 0.00001, OR = 0.43, 95% CI (0.37-0.50)) and rs7517847
      (G/G vs. T/T, P < 0.00001, OR = 0.49, 95% CI (0.38-0.64); G/G vs. T/G + T/T, (P <
      0.00001, OR = 0.56, 95% CI (0.44-0.72); T/G + G/G vs. T/T, (P < 0.00001, OR =
      0.71, 95% CI (0.64-0.79) of IL-23R were inversely associated with CD risk;
      sensitivity analysis also indicated that Caucasian population with a variant of
      Arg381Gln has a decreased risk for developing CD (P < 0.00001, OR = 0.43, 95% CI
      (0.36-0.50)). CONCLUSION: Our meta-analysis supports that two polymorphisms
      (Arg381Gln and rs7517847) within the IL-23R gene may be considered to be
      protective factors against developing CD. Further large case-control studies
      especially concerning ethnicity differences and genotype-phenotype interaction
      should be performed to clarify possible roles of IL-23R in CD.

PMID- 20157761
TI  - Production of thermotolerant entomopathogenic Isaria fumosorosea SFP-198 conidia
      in corn-corn oil mixture.
AB  - Low thermotolerance of entomopathogenic fungi is a major impediment to long-term
      storage and effective application of these biopesticides under seasonal high
      temperatures. The effects of high temperatures on the viability of an
      entomopathogenic fungus, Isaria fumosorosea SFP-198 (KCTC 0499BP), produced on
      different substrates amended with various additives were explored. Ground corn
      was found to be superior in producing the most thermotolerant conidia compared to
      yellow soybean, red kidney bean, and rice in a polyethylene bag production
      system. Using ground corn mixed with corn oil as a substrate resulted in only 7%
      reduction in germination compared to ground corn alone (67% reduction) after
      exposure of conidia to 50 degrees C for 2 h. Corn oil as an additive for ground
      corn was followed by inorganic salts (KCl and NaCl), carbohydrates (sucrose and
      dextrin), a sugar alcohol (sorbitol), and plant oils (soybean oil and cotton seed
      oil) in ability to improve conidial thermotolerance. Unsaturated fatty acids,
      such as linoleic acid and oleic acid, the main components of corn oil, served as
      effective additives for conidial thermotolerance in a dosage-dependent manner,
      possibly explaining the improvement by corn oil. This finding suggests that the
      corn-corn oil mixture can be used to produce highly thermotolerant SFP-198
      conidia and provides the relation of unsaturated fatty acids as substrates with
      conidial thermotolerance.

PMID- 20157762
TI  - HGF upregulates CXCR4 expression in gliomas via NF-kappaB: implications for
      glioma cell migration.
AB  - Invasion is a hallmark of malignant gliomas and is the main reason for
      therapeutic failure and recurrence of the tumor. CXCR4 is a key chemokine
      receptor implicated in glioma cell migration whose expression is regulated by
      hypoxia. Here, we report that hepatocyte growth factor (HGF) upregulated CXCR4
      protein expression in glioma cells. HGF pre-treatment increased migration of
      U87MG and LN229 glioma cells towards the CXCR4 ligand, stromal cell-derived
      factor-1alpha (SDF-1alpha). AMD3100, a CXCR4 inhibitor, inhibited the increased
      migration of HGF pre-treated LN229 glioma cells towards SDF-1alpha. Following
      exposure to HGF and hypoxia, both cell lines showed nuclear translocation of NF
      kappaB (p65). The HGF- and hypoxia-induced nuclear translocation of NF-kappaB
      (p65) involved phosphorylation and degradation of IkappaB-alpha. Knock-down of NF
      kappaB expression inhibited the induction of CXCR4 expression in response to HGF,
      but not to hypoxia. However, knock-down of NF-kappaB expression inhibited the
      induction of CXCR4 expression in response to hypoxia in the presence of HGF. NF
      kappaB mediated migration towards SDF-1alpha in response to HGF. Knock-down of NF
      kappaB expression resulted in decreased migration of HGF pre-treated glioma cells
      towards SDF-1alpha. Therefore, HGF upregulates CXCR4 expression via NF-kappaB and
      leads to enhanced migration. To our knowledge, this is the first report to show
      that a crosstalk mediated by NF-kappaB exists between the SDF-1alpha/CXCR4 and
      HGF/c-Met axes relevant to glioma cell migration. These findings imply that
      effective inhibition of glioma invasion should be directed against several
      ligand/receptor signaling pathways.

PMID- 20157763
TI  - Evaluation of the cytoprotective effects of bovine lactoferrin against intestinal
      toxins using cellular model systems.
AB  - Lactoferrin is an iron-binding glycoprotein that exhibits a range of health
      benefits including immune regulation and disease prevention derived from its
      structural properties. The present study employed immune cell models and a colon
      epithelial cell model to investigate the protective effects of bovine lactoferrin
      (BLf) on both immune cells and colon epithelium cells. BLf caused significant
      reduction of faecal genotoxin-induced DNA damage in HT29 cells, and down
      regulation of lipopolysaccharide (LPS)-induced macrophage cell stress and
      endotoxic response, in an infection status.

PMID- 20157764
TI  - Salt-induced expression of genes related to Na(+)/K(+) and ROS homeostasis in
      leaves of salt-resistant and salt-sensitive poplar species.
AB  - Using the Affymetrix poplar genome array, we explored the leaf transcriptome of
      salt-tolerant Populus euphratica Oliv. and salt-sensitive P. popularis 35-44 (P.
      popularis) under control and saline conditions. Our objective was to clarify the
      genomic differences in regulating K(+)/Na(+) and reactive oxygen species (ROS)
      homeostasis between the two species. Compared to P. popularis, salt-tolerant P.
      euphratica responses to salinity involved induction of a relatively larger number
      of probesets after short-term (ST) exposure to 150 mM NaCl (24 h) and relatively
      fewer probesets after a long-term (LT) exposure to salinity (200 mM NaCl, 28
      days). Compared to P. popularis, leaves of the control P. euphratica plants
      exhibited a higher transcript abundance of genes related to Na(+)/H(+) antiport
      (Na(+)/H(+) antiporters, H(+) pumps) and K(+) uptake and transport. Notably, the
      expression of these genes did not decrease (with a few exceptions) during salt
      treatment. Regarding ROS homeostasis, P. euphratica exhibited rapid up-regulation
      of a variety of antioxidant enzymes after exposure to ST salinity, indicating a
      rapid adaptive response to salt stress. However, the effect of NaCl on
      transcription in P. popularis leaves was more pronounced after exposure to
      prolonged salinity. LT-stressed P. popularis up-regulated some genes mediating
      K(+)/Na(+) homeostasis but decreased transcription of main scavengers of
      superoxide radicals and H(2)O(2) except for some isoforms of a few scavengers.
      Mineral and ROS analyses show that NaCl induced a marked increase of leaf Na(+)
      and H(2)O(2) in LT-stressed plants of the two species and the effects were even
      more pronounced in the salt-sensitive poplar. We place the transcription results
      in the context of our physiological measurements to infer some implications of
      NaCl-induced alterations in gene expression related to K(+)/Na(+) and ROS
      homeostasis.

PMID- 20157765
TI  - CBP knockdown inhibits angiotensin II-induced vascular smooth muscle cells
      proliferation through downregulating NF-kB transcriptional activity.
AB  - CREB binding protein (CBP), a powerful transcriptional co-activator for various
      transcriptional factors, regulates cell behavior in many cell types. Angiotensin
      II (Ang II) contributes to vascular lesion by promoting vascular smooth muscle
      cells (VSMCs) proliferation and migration. Therefore, we examined whether CBP
      knockdown could suppress Ang II-induced VSMCs proliferation, and elucidated its
      underlying molecular mechanism. We constructed lentiviral vector expressing CBP
      specific short hairpin RNAs (shRNAs) that efficiently silenced CBP. VSMCs
      proliferation was evaluated by bromodeoxyuridine (BrdU) incorporation assay.
      Protein and mRNA expression of CBP and relevant cytokines were examined by
      Western blot, ELISA, and real-time PCR, respectively. We also used luciferase
      reporter gene and electrophoretic mobility shift assay (EMSA) to detect Nuclear
      factor kappaB (NF-kB) transcriptional activity and DNA binding. Meanwhile, NF-kB
      p65 subunit nuclear translocation was confirmed by immunoblotting. Lentiviral
      mediated CBP-shRNAs at different multiplicities of infection (MOI = 100, 150)
      both significantly suppressed Ang II-induced CBP expression. Knockdown of CBP
      markedly inhibited Ang II-stimulated VSMCs proliferation and cytokines (TNF-alpha
      and IL-6) production. However, this inhibitory effect was not enhanced at MOI of
      150 compared with MOI of 100 (P > 0.05). CBP siRNA showed the potent inhibition
      on Ang II-induced NF-kB transcriptional activity. Similarly, no significant
      difference was found between CBP siRNA lentivirus treatment groups. Furthermore,
      CBP gene silencing had no effect on NF-kB nuclear translocation and DNA binding.
      These findings suggest that CBP knockdown inhibits Ang II-induced VSMCs
      proliferation and the mechanism is involved with downregulation of NF-kB
      transcriptional activity, not through reduction in NF-kB nuclear translocation or
      DNA binding. Maintaining proper CBP level may be a potential therapeutic target
      for Ang II-induced cardiovascular disorders.

PMID- 20157766
TI  - Notch signaling maintains proliferation and survival of the HL60 human
      promyelocytic leukemia cell line and promotes the phosphorylation of the Rb
      protein.
AB  - The Notch signaling pathway has been implicated in the development of several
      leukemia and lymphoma. In order to investigate the relationship between Notch
      signaling and acute myeloid leukemia (AML), in this study, we expressed a
      recombinant Notch ligand protein, the DSL domain of the human Jagged1 fused with
      GST (GST-Jag1). GST-Jag1 could activate Notch signaling in the human
      promyelocytic leukemia cell line HL60, as shown by a reporter assay and the
      induced expression of Notch effector gene Hes1 and Hes5. However, GST-Jag1 had no
      effect on the proliferation and survival of HL60 cells. HL60 cells expressed both
      Notch ligands and receptors, and had a potential of reciprocal stimulation of
      Notch signaling between cells. We, therefore, blocked Notch signaling in cultured
      HL60 cells using a gamma-secretase inhibitor (GSI). We found that GSI inhibited
      the proliferation of HL60 cells significantly by blocking the cell-cycle
      progression in the G1 phase. Furthermore, GSI induced remarkably apoptosis of
      HL60 cells. These changes in GSI-treated HL60 cells correlated with the down
      regulation of c-Myc and Bcl2, and the low phosphorylation of the Rb protein.
      These results suggested that reciprocal Notch signaling might be necessary for
      the proliferation and survival of AML cells, possibly through the maintenance of
      the expression of c-Myc and Bcl2, as well as the phosphorylation of the Rb
      protein.

PMID- 20157767
TI  - Lefty A attenuates the TGF-beta1-induced epithelial to mesenchymal transition of
      human renal proximal epithelial tubular cells.
AB  - The epithelial to mesenchymal transition (EMT) is a crucial event for renal
      fibrosis that can be elicited by TGF-beta1/Smads signaling and its downstream
      mediator connective tissue growth factor (CTGF). As a distinct member of the TGF
      beta superfamily, Lefty A has been shown to be significantly downregulated in the
      kidneys of patients with severe ureteral obstruction, suggesting its role in
      renal fibrosis induced by obstructive nephropathy. In order to determine whether
      Lefty A prevents TGF-beta1-induced EMT, human proximal tubule epithelial cells
      (HK-2) were stably transfected with Lefty A or control vectors and stimulated
      with 10 ng/ml TGF-beta1 for 48 h. The results show that stimulation with TGF
      beta1 led to EMT including cell morphology changes, Smad2/3 signaling pathway
      activation, increased alpha-SMA, collagen type I, and CTGF expression, and
      decreased E-cadherin expression in mock-transfected HK-2 cells. Overexpression of
      Lefty A efficiently blocked p-Smad2/3 activation and attenuated all these EMT
      changes induced by TGF-beta1. This finding suggests that Lefty A may serve as a
      potential new therapeutic target to inhibit or even reverse EMT during the
      process of renal fibrosis.

PMID- 20157768
TI  - Comparative expression of laminin and smooth muscle actin in the testis and
      epididymis of poultry and rabbit.
AB  - The present investigation was conducted to demonstrate laminin and alpha smooth
      muscle actin (alphaSMA) in the testis and epididymis of adult chickens, Sudani
      ducks, pigeons, and rabbits. This study may represent the first indication for
      the presence of laminin in the male reproductive organs of birds and rabbits and
      might therefore serve as a milestone for further reports. In the testis of
      chicken, Sudani duck, pigeon, and rabbit, the laminin was localized in the basal
      lamina of the seminiferous tubules and of the peritubular myoid cells, in the
      testicular capsule and to a small extent in the vicinity of Leydig cells. The
      testicular vasculature also exhibited intense laminin immunostaining. Weak
      laminin staining was additionally seen in the cytoplasm of the duck Sertoli
      cells. In the epididymis, the basal lamina of the epididymal epithelium showed a
      distinctly positive reaction in all birds and rabbit. The basal lamina of the
      periductal myoid cells also showed a positive reaction. In the interductal
      tissue, laminin immunostaining was particularly observed in chicken, duck and
      pigeon. Laminin positive reaction was also seen in the epididymal vasculatures of
      all birds and rabbit. Interestingly, weak to moderate laminin staining was
      observed in the apical surface of the ciliated cells of the proximal and distal
      efferent ductules in chicken, duck and pigeon. alphaSMA positive reaction was
      seen in the testicular capsule and in the peritubular myoid cells of all birds
      and rabbit. In the testicular capsule, alphaSMA staining was either observed in
      the inner portion (chicken) or throughout the tunica albuginea (Sudani duck and
      pigeon), or in the outer aspect (rabbit). Distinct alphaSMA reaction was
      additionally observed in the testicular vasculature. In the epididymis of all
      birds and rabbit, the alphaSMA was particularly seen in the periductal and
      interductal myoid cells as well as in the epididymal vasculatures. No alphaSMA
      specific staining was however detected in the epididymal epithelium, fibrous
      lamina propria, and luminal spermatozoa of all birds and rabbits. In conclusion,
      the distribution of laminin and alphaSMA in the testis and epididymis might point
      out to their roles in the male reproduction.

PMID- 20157769
TI  - Phosphatidylinositol 3'-kinase signalling supports cell height in established
      epithelial monolayers.
AB  - Cell-cell interactions influence epithelial morphogenesis through an interplay
      between cell adhesion, trafficking and the cytoskeleton. These cellular processes
      are coordinated, often by cell signals found at cell-cell contacts. One such
      contact-based signal is the phosphatidylinositol 3'-kinase (PI3-kinase; PI3K)
      pathway. PI3-kinase is best understood for its role in mitogenic signalling,
      where it regulates cell survival, proliferation and differentiation. Its precise
      morphogenetic impacts in epithelia are, in contrast, less well-understood. Using
      phosphoinositide-specific biosensors we confirmed that E-cadherin-based cell-cell
      contacts are enriched in PIP(3), the principal product of PI3-kinase. We then
      used pharmacologic inhibitors to assess the morphogenetic impact of PI3-kinase in
      MDCK and MCF7 monolayers. We found that inhibiting PI3-kinase caused a reduction
      in epithelial cell height that was reversible upon removal of the drugs. This was
      not attributable to changes in E-cadherin expression or homophilic adhesion. Nor
      were there detectable changes in cell polarity. While Myosin II has been
      implicated in regulating keratinocyte height, we found no effect of PI3-kinase
      inhibition on apparent Myosin II activity; nor did direct inhibition of Myosin II
      alter epithelial height. Instead, in pursuing signalling pathways downstream of
      PI3-kinase we found that blocking Rac signalling, but not mTOR, reduced
      epithelial cell height, as did PI3-kinase inhibition. Overall, our findings
      suggest that PI3-kinase exerts a major morphogenetic impact in simple cultured
      epithelia through preservation of cell height. This is independent of potential
      effects on adhesion or polarity, but may occur through PI3-kinase-stimulated Rac
      signaling.

PMID- 20157771
TI  - Full genomic analysis and possible origin of a porcine G12 rotavirus strain
      RU172.
AB  - Human group A rotavirus (GAR) G12 strains are regarded as potentially important
      pathogens for acute gastroenteritis. On the other hand, to date, the only report
      of detection of G12 in animals was that of a porcine G12P[7] strain RU172. Strain
      RU172 formed a separate G12 lineage, distinct from human G12 strains, and by
      analyses of deduced amino acid sequences, had a VP4, VP6, NSP4-5 of porcine
      origin. In the present study, we determined the full-length nucleotide sequences
      of VP1, VP3, and NSP1-3 genes and nearly full-length nucleotide sequence of VP2
      gene of RU172. By nucleotide sequence identities and phylogenetic analyses, the
      VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes of RU172 were assigned to
      G12-P[7]-I5-R1-C1-M1-A1-N1-T1-E1-H1 genotypes, respectively. Within their
      respective genotypes, (i) VP1 gene of RU172 exhibited higher genetic relatedness
      to Wa-like human G12 GARs than porcine strains, (ii) VP2-3 and NSP2 genes
      clustered separately from the Wa-like human (including G12) and porcine clusters,
      while (iii) the VP6, NSP1 and NSP3-5 genes clustered with porcine and porcine
      like human strains. These observations suggested that (i) the porcine G12 strain
      might have originated from porcine-human reassortment events, or alternatively,
      (ii) the Wa-like human and porcine G12 strains might have originated from a
      common ancestor, and eventually evolved (by genetic drift and shift) with time.
      Our findings provided important insights into the possible patterns of evolution
      of the porcine G12 strain.

PMID- 20157772
TI  - Human alpha and beta papillomaviruses use different synonymous codon profiles.
AB  - Human papillomaviruses use rare codons relative to their hosts. It has been
      theorized that this is a mechanism to allow the virus to escape immune
      surveillance. In the present study, we examined the codings of four major genes
      of 21 human alpha (mucosatropic) viruses and 16 human beta (cutaneous-tropic)
      viruses. We compared the codon usage of different genes from a given
      papillomavirus and also the same genes from different papillomaviruses. Our data
      showed that codon usage was not always uniform between two genes of a given
      papillomavirus or between the same genes of papillomaviruses from different
      genera. We speculate as to why this might be and conclude that codon usage in the
      papillomaviruses may not only play a role in facilitating escape from immune
      surveillance but may also underlie some of the unanswered questions in the
      papillomavirus field.

PMID- 20157770
TI  - The epigenetic landscape of mammary gland development and functional
      differentiation.
AB  - Most of the development and functional differentiation in the mammary gland occur
      after birth. Epigenetics is defined as the stable alterations in gene expression
      potential that arise during development and proliferation. Epigenetic changes are
      mediated at the biochemical level by the chromatin conformation initiated by DNA
      methylation, histone variants, post-translational modifications of histones, non
      histone chromatin proteins, and non-coding RNAs. Epigenetics plays a key role in
      development. However, very little is known about its role in the developing
      mammary gland or how it might integrate the many signalling pathways involved in
      mammary gland development and function that have been discovered during the past
      few decades. An inverse relationship between marks of closed (DNA methylation) or
      open chromatin (DnaseI hypersensitivity, certain histone modifications) and milk
      protein gene expression has been documented. Recent studies have shown that
      during development and functional differentiation, both global and local
      chromatin changes occur. Locally, chromatin at distal regulatory elements and
      promoters of milk protein genes gains a more open conformation. Furthermore,
      changes occur both in looping between regulatory elements and attachment to
      nuclear matrix. These changes are induced by developmental signals and
      environmental conditions. Additionally, distinct epigenetic patterns have been
      identified in mammary gland stem and progenitor cell sub-populations. Together,
      these findings suggest that epigenetics plays a role in mammary development and
      function. With the new tools for epigenomics developed in recent years, we now
      can begin to establish a framework for the role of epigenetics in mammary gland
      development and disease.

PMID- 20157773
TI  - Body size and risk of prostate cancer in Jamaican men.
AB  - We investigated the associations between body size and risk of prostate cancer in
      a hospital-based case-control study in Jamaica. Height, weight, waist, and hip
      circumference were measured at enrollment, and data collected on medical and
      lifestyle factors for newly diagnosed cases (n = 243) and controls (n = 275).
      Compared with men in the normal range of waist-hip ratio (WHR), men with WHR > or
      =0.95 were at greater risk of total prostate cancer (OR,1.72; CI, 1.01-3.00) and
      high-grade cancer (OR, 2.02; CI, 1.03-3.96). With additional control for BMI, the
      association with WHR remained significant for total prostate cancer (OR, 1.90;
      CI, 1.01-3.53) and high-grade disease (OR, 2.94; CI, 1.34-6.38). There was no
      association between waist circumference and cancer without control for BMI but
      after controlling for BMI, waist circumference >90 cm (OR, 2.45; CI, 1.01-5.94)
      and >102 cm (OR, 5.57; CI, 1.43-18.63) showed a dose-response relationship with
      high-grade disease. Height and BMI were not associated with risk of prostate
      cancer. Abdominal obesity may be associated with risk of high-grade prostate
      cancer. Risk may be greater in those with higher abdominal obesity relative to
      overall size. The results further highlight the importance of investigating
      relationships by characteristics of the tumor.

PMID- 20157774
TI  - Tocotrienols induce apoptosis in breast cancer cell lines via an endoplasmic
      reticulum stress-dependent increase in extrinsic death receptor signaling.
AB  - Tocotrienols are naturally occurring forms of vitamin E based on their structural
      similarity. This study focused on investigating anticancer effects of
      tocotrienols and the mechanisms of apoptosis induction by tocotrienols in vivo
      and in vitro. Dietary delivery of gamma-tocotrienol (gamma-T3) suppressed tumor
      growth in a syngeneic implantation mouse mammary cancer model by inhibiting cell
      proliferation and inducing apoptosis. In cell culture studies, gamma-T3 inhibited
      colony formation of a mouse mammary cancer cell line and human breast cancer cell
      lines. The anti-proliferative effects of tocotrienols were highly correlated with
      an increase in apoptosis based on Annexin V assessment. Treatment of human MDA-MB
      231 and MCF-7 cells with gamma-T3 induced cleavages of PARP as well as caspase-8,
      -9, and -3. Additional analyses showed that gamma-T3 activated c-Jun NH(2)
      terminal kinase (JNK) and p38 MAPK, and upregulated death receptor 5 (DR5) and
      C/EBP homologous protein (CHOP), an endoplasmic reticulum (ER) stress marker.
      Silencing either JNK or p38 MAPK reduced the increase in DR5 and CHOP and
      partially blocked gamma-T3-induced apoptosis. Both DR5 and CHOP upregulation were
      required for gamma-T3-induced apoptosis, and DR5 was transcriptionally regulated
      by CHOP after gamma-T3 treatment. Moreover, gamma-T3 increased the level of other
      ER-stress markers. Taken together, these results suggest that upregulation of DR5
      by gamma-T3 treatment is dependent on JNK and p38 MAPK activation which is
      mediated by ER-stress.

PMID- 20157775
TI  - TGFB1 T29C polymorphism and breast cancer risk: a meta-analysis based on 10,417
      cases and 11,455 controls.
AB  - Breast cancer is the most prevalent cancer worldwide. Many published articles
      have evaluated the association between the transforming growth factor beta 1
      (TGFB1) T29C polymorphism and breast cancer risk. However, the results remain
      inconclusive. In order to derive a more precise estimation of the association, a
      meta-analysis was performed in this study. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were used to assess the strength of the association. A total of
      12 studies including 10,417 breast cancer cases and 11,455 controls were
      identified. Overall, no significant associations between the TGFB1 T29C
      polymorphism and breast cancer risk were found for CC versus TT (OR = 1.00, 95%
      CI = 0.92-1.09), TC versus TT (OR = 0.98, 95% CI = 0.93-1.05), CC/TC versus TT
      (OR = 0.99, 95% CI = 0.93-1.05), and CC versus TC/TT (OR = 1.00, 95% CI = 0.93
      1.08). In the subgroup analysis by ethnicity, source of controls, and menopausal
      status, there was still no significant association detected in all genetic
      models. In conclusion, the present meta-analysis suggests that the TGFB1 T29C
      polymorphism is not a low-penetrant risk factor for developing breast cancer.

PMID- 20157776
TI  - Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know
      and how can we find out more?
AB  - Aromatase inhibitors (AIs) are a standard of care for the adjuvant treatment of
      hormone responsive early carcinoma of the breast as demonstrated in a number of
      large international phase III randomised trials. Arthralgia was a somewhat
      unexpected side effect of this class of agents and has proven to be potentially
      problematic in clinical practice. Although rates of up 35% have been reported in
      the randomised trials, the figure has been much higher in subsequent case series.
      There is concern that these symptoms are significant and may affect compliance
      and thus the overall efficacy of treatment. It is therefore extremely important
      that we evaluate this syndrome with a view to gaining more information regarding
      its clinical features and possible aetiological mechanism. The potential
      aetiological mechanisms and evidence for aromatase inhibitor-induced arthralgia
      (AIA) are reviewed in this article. Looking forward, it is now important that
      prospective clinical trials are well designed to evaluate this syndrome and
      potential therapeutic strategies to circumvent it. Radiological imaging and
      biochemical analyses may help our understanding of AIA and these are discussed.

PMID- 20157777
TI  - A novel and facile synthesis of N-cyclohexyl-benzofurans by one-pot three
      component reaction.
AB  - A simple and efficient synthesis of N-cyclohexyl-benzofuran derivatives was
      achieved via a one-pot three-component reaction of cyclohexylisocyanide, an
      aromatic aldehydes, and phenols in DMF for 10 h with good yields.

PMID- 20157778
TI  - Three-component synthesis of benzo[b][1,5]thiazepines via coupling-addition
      cyclocondensation sequence.
AB  - 2,4-Disubstituted benzo[b][1,5]thiazepines represent nonfluorescent intense
      yellow chromophores and are readily synthesized from acid chlorides, terminal
      alkynes, and ortho-amino thiophenols by a consecutive one-pot three-component
      Sonogashira coupling-Michael addition-cyclocondensation sequence under mild
      conditions in good yields.

PMID- 20157779
TI  - Genetic, epigenetic and posttranslational mechanisms of aging.
AB  - Gerontological experimentation is and was always strongly influenced by
      "theories". The early decades of molecular genetics inspired deterministic
      thinking, based on the "Central Dogma" (DNA --> RNA --> Proteins). With the
      progress of detailed knowledge of gene-function a much more complicated picture
      emerged. Regulation of gene-expression turned out to be a highly complicated
      process. Experimental gerontology produced over the last decades several
      "paradigms" incompatible with simple genetic determinism. The increasing number
      of such detailed experimental "facts" revealed the importance of epigenetic
      factors and of posttranslational modifications in the age-dependent decline of
      physiological functions. We shall present in this review a short but critical
      analysis of genetic and epigenetic processes applied to the interpretation of the
      more and more precisely elucidated experimental paradigms of aging followed by
      some of the most relevant aging-mechanisms at the post-translational level, the
      posttranslational modifications of proteins such as the Maillard reaction, the
      proteolytic production of harmful peptides and the molecular mechanisms of the
      aging of elastin with the role of the age-dependent uncoupling of the elastin
      receptor, as well as the loss of several other receptors. We insist also on the
      well documented influence of posttranslational modifications on gene expression
      and on the role of non-coding RNA-s. Altogether, these data replace the previous
      simplistic concepts on gene action as related to aging by a much more complicated
      picture, where epigenetic and posttranslational processes together with
      environmentally influenced genetic pathways play key-roles in aging and strongly
      influence gene expression.

PMID- 20157780
TI  - Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and
      necrotic cells.
AB  - Tissue homeostasis in metazoa requires the rapid and efficient clearance of dying
      cells by professional or semi-professional phagocytes. Impairment of this finely
      regulated, fundamental process has been implicated in the development of
      autoimmune diseases, such as systemic lupus erythematosus. Various studies have
      provided us a detailed understanding of the interaction between dying cells and
      phagocytes as well as the current concept that apoptotic cell removal leads to a
      non- or anti-inflammatory response, whereas necrotic cell removal stimulates a
      pro-inflammatory reaction. In contrast, our knowledge about the soluble factors
      released from dying cells is rather limited, although meanwhile it is generally
      accepted that not only the dying cell itself but also the substances liberated
      during cell death contribute to the process of corpse clearance and the
      subsequent immune response. This review article is intended as an up-to-date
      survey over attraction and danger signals of apoptotic, primary and secondary
      necrotic cells, their function as chemoattractants in phagocyte recruitment,
      additional effects on the immune system, and the receptors, which are engaged in
      this scenario.

PMID- 20157781
TI  - Chorionic villi ultrastructure in the prenatal diagnosis of glycogenosis type II.
AB  - OBJECTIVE: To perform the ultrastructural examination of a chorionic villi biopsy
      as a predictor of foetal involvement in the infantile form of glycogenosis type
      II (Pompe disease). METHODS: Ultrastructural, biochemical and genetic analyses
      were performed on chorionic villi biopsies of three consecutive pregnancies in a
      woman with a previous child affected by Pompe disease. RESULTS: In the only
      affected foetus, glycogen storage was observed in fibrocytes and endothelial
      cells of a chorionic villi sample at 11 week's gestation. Severe multi-organ
      involvement was demonstrated in the tissues of the aborted foetus. No abnormal
      material was found in the chorionic samples of two subsequent pregnancies, and a
      healthy boy and girl were born at term and remain unaffected. Both exhibited a
      partial reduction in acid maltase and were carriers of the maternal mutation.
      CONCLUSIONS: Ultrastructural findings correlated with biochemical and genetic
      results, providing a clear and early indicator of the definite diagnosis for
      future pregnancy management or an early therapeutic approach.

PMID- 20157782
TI  - The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by
      expanded newborn metabolic screening in Italy: the importance of an integrated
      diagnostic approach.
AB  - A pilot expanded newborn screening programme to detect inherited metabolic
      disorders by means of liquid chromatography coupled with tandem mass spectrometry
      (LC-MS/MS) began in the Campania region, southern Italy, in 2007. By October
      2009, >8,800 dried blood samples on filter paper from 11 hospitals had been
      screened. Within this screening programme, we identified a case of mitochondrial
      acetoacetyl-coenzyme A (CoA) thiolase deficiency [beta-ketothiolase (beta-KT)
      deficiency] by analysing the acylcarnitine profile from a dried blood spot with
      LC-MS/MS. Gas chromatography coupled with mass spectrometry analysis of urinary
      organic acids and LC-MS/MS analysis of urinary acylcarnitines were in line with
      this disorder. In fact, concentrations were well beyond the cut-off values of
      tiglyl carnitine, 3-hydroxybutyrylcarnitine and 2-methyl-3
      hydroxybutyrylcarnitine, 2-methyl-3-hydroxybutyric acid and tiglyl glycine. The
      absence of 2-methylacetoacetic acid in urine may be attributed to: (i) the
      instability of this beta-ketoacid because it undergoes spontaneous
      decarboxylation to 2-butanone, which is highly volatile and thus difficult to
      detect, and (ii) the good health of the patient in the first days of life. beta
      KT deficiency was subsequently diagnosed in the patient's older sister, who
      showed increased levels of the same metabolites but also small amounts of 2
      methylacetoacetic acid, which is considered a key marker for beta-KT diagnosis.
      Genomic analysis revealed mutation c.1189C >G in exon 12 of the ACAT1 gene, which
      results in a severe defect because of the p.H397D amino acid change in both
      alleles of both patients. 

PMID- 20157783
TI  - Measuring cellular immunity in coccidioidomycosis: the time is now.

PMID- 20157784
TI  - Cancer family history characterization in an unselected cohort of 121 patients
      with uveal melanoma.
AB  - Uveal melanoma (UM) is the most common primary intraocular malignancy in adults.
      The extent of the contribution of familial/hereditary predisposition to the
      development of uveal melanoma is largely unknown. Thus we sought to ascertain the
      frequency of cancers in patients with UM and their family members to identify the
      prevalence of hereditary/familial predisposition to cancer in these patients. An
      unselected series of 121 patients with UM seen in a university-based tertiary
      referral program were consented to the study. Cancer histories (site and age of
      diagnosis) were obtained for all first- and second-degree relatives.
      Patients/families were classified as being potentially at high risk for
      hereditary predisposition if they met any of the following criteria: (1)
      Diagnosis of UM at age 30 or under, (2) Two or more cases of UM in the family,
      (3) UM plus at least one other primary cancer in the same patient (excluding non
      melanoma skin and cervix cancers due to their strong environmental etiological
      link). (4) Family history meeting high risk criteria for a known hereditary
      cancer predisposition syndrome as defined by Hampel et al. (J Med Genet 41(2): 81
      91, 2004). One patient had a family history of UM (0.8%). Ten patients (8.3%) had
      a personal and/or family history consistent with predisposition to a known
      hereditary cancer syndrome including six with possible hereditary breast, two
      with hereditary colon and two with hereditary melanomas. Twenty three patients
      (19%) had a personal history of a second cancer after exclusion of non-melanoma
      skin and cervical cancers. The frequency of cutaneous melanomas was significantly
      higher in UM patients than the general population (RR: 2.97, 95% CI: 1.00-6.94).
      Patients with a family history suggestive of a high risk predisposition to a
      known cancer syndrome had a significantly higher risk for having a second cancer
      than the remaining UM patients (P = 0.02). Our results indicate that the
      frequency of UM patients with high risk for a hereditary cancer predisposition is
      much higher than earlier estimates (0.6%) and that it could be as high as 11.6%.
      Our results suggest that cancer phenotypes in these patients are diverse and
      include cancers other than UM. Thus, alerting ophthalmologists to the need for
      expanding their cancer family history intake to include other cancers is
      warranted. It also suggests that patients with a hereditary predisposition to UM
      have a higher risk for the development of other cancers and that characterization
      of the germline genetic alterations in these patients is highly warranted.

PMID- 20157785
TI  - Therapeutic effect of Linum usitatissimum (flaxseed/linseed) fixed oil on acute
      and chronic arthritic models in albino rats.
AB  - The present study was undertaken to assess the activity/anti-inflammatory
      potential of Linum usitatissimum fixed oil against castor oil-induced diarrhoea,
      turpentine oil-induced joint oedema, formaldehyde and Complete Freund's Adjuvant
      (CFA)-induced arthritis in Wistar albino rats. The oil intraperitoneally,
      significantly inhibited the castor oil-induced diarrhoea and turpentine oil
      induced exudative joint oedema in a dose-dependent manner. Significant inhibitory
      effect of L. usitatissimum fixed oil was observed in formaldehyde-induced
      proliferative global oedematous arthritis when given intraperitoneally, with
      significant checking of the serum glutamic oxaloacetic acid transaminase and
      serum glutamic pyruvic acid transaminase. Further, L. usitatissimum fixed oil
      showed a significant dose-dependent protective effect against CFA-induced
      arthritis as well. Secondary lesions produced by CFA due to a delayed
      hypersensitivity reaction were also reduced in a significant manner. Anti
      inflammatory activity of L. usitatissimum fixed oil can be attributed to the
      presence of alpha linolenic acid (57.38%, an omega-3 fatty acid, 18:3, n-3)
      having dual inhibitory effect on arachidonate metabolism resulting in suppressed
      production of proinflammatory n-6 eicosanoids (PGE(2), LTB(4)) and diminished
      vascular permeability. These observations suggest possible therapeutic potential
      of L. usitatissimum fixed oil in inflammatory disorders like rheumatoid
      arthritis.

PMID- 20157786
TI  - Dysregulation of the receptor activator of NF-kappaB ligand and osteoprotegerin
      production influence the apoptosis of multiple myeloma patients' bone marrow
      stromal cells co-cultured with myeloma cells.
AB  - The interaction of multiple myeloma (MM) cells and bone marrow stromal cells
      (BMSCs) induces profound changes in the bone marrow environment, influencing
      osteoclastogenesis and MM cell survival. Differences in receptor activator of NF
      kappaB ligand (RANKL) and osteoprotegerin (OPG) production in BMSCs derived from
      MM patients and control subjects and the apoptosis of BMSCs and MM cells in co
      cultures of both cell types were examined. RANKL and OPG expressions were
      examined by ELISA and semiquantitative RT-PCR. Apoptosis of BMSCs after contact
      with RPMI8226 and U266 cells was measured by flow cytometry and the level of ALP
      activity by the spectrophotometric method. OPG production by BMSCs was
      significantly inhibited after direct contact with RPMI8226 cells. Production of
      soluble RANKL was enhanced and the increase was more significant in the BMSCs of
      the MM patients than in those of the controls. In co-cultures of BMSCs and MM
      cells, significant apoptosis was detected with a concomitant decrease in ALP
      activity. This apoptosis decreased significantly in the presence of RANK-Fc, an
      antagonist of RANKL. Disturbances in the RANKL/OPG system are more profound in
      the BMSCs of MM patients than in those of control subjects after direct contact
      with RPMI8226 cells. Moreover, direct contact with RPMI8226 and U266 cells
      induces apoptosis of BMSCs which is mediated by an overproduction of RANKL.

PMID- 20157787
TI  - Histone deacetylase inhibitors suppress the expression of inflammatory and innate
      immune response genes in human microglia and astrocytes.
AB  - Histone deacetylase inhibitors (HDACi) have been proposed as therapies for
      certain cancers and as an anti-reservoir therapy for HIV+ individuals with highly
      active anti-retroviral therapy, yet their roles in glial inflammatory and innate
      antiviral gene expression have not been defined. In this study, we examined the
      effects of two non-selective HDACi, trichostatin A and valproic acid, on
      antiviral and cytokine gene expression in primary human microglia and astrocytes
      stimulated with TLR3 or TLR4 ligand. HDACi potently suppressed the expression of
      innate antiviral molecules such as IFNbeta, interferon-simulated genes, and
      proteins involved in TLR3/TLR4 signaling. HDACi also suppressed microglial and
      astrocytic cytokine and chemokine gene expression, but with different effects on
      different groups of cytokines. These results have important implications for the
      clinical use of HDACi.

PMID- 20157788
TI  - Limb occlusion after endovascular repair of an abdominal aortic aneurysm: beware
      the narrow distal aorta.
AB  - PURPOSE: This case aims to highlight the need for careful scrutiny of the distal
      aorta during endovascular aneurysm repair (EVAR) planning to avoid potentially
      avoidable graft limb occlusion. CASE REPORT: We present a case of graft limb
      occlusion after EVAR, unresponsive to endovascular re-intervention requiring
      surgical extra-anatomic revascularization, due to a narrow distal aorta causing
      graft impingement and collapse. CONCLUSION: We suggest clinicians should be aware
      of this potential pitfall during EVAR planning and beware the narrow distal
      aorta.

PMID- 20157789
TI  - Reperfusion and neurovascular dysfunction in stroke: from basic mechanisms to
      potential strategies for neuroprotection.
AB  - Effective stroke therapies require recanalization of occluded cerebral blood
      vessels. However, reperfusion can cause neurovascular injury, leading to cerebral
      edema, brain hemorrhage, and neuronal death by apoptosis/necrosis. These
      complications, which result from excess production of reactive oxygen species in
      mitochondria, significantly limit the benefits of stroke therapies. We have
      developed a focal stroke model using mice deficient in mitochondrial manganese
      superoxide dismutase (SOD2-/+) to investigate neurovascular endothelial damage
      that occurs during reperfusion. Following focal stroke and reperfusion, SOD2-/+
      mice had delayed blood-brain barrier breakdown, associated with activation of
      matrix metalloproteinase and high brain hemorrhage rates, whereas a decrease in
      apoptosis and hemorrhage was observed in SOD2 overexpressors. Thus, induction and
      activation of SOD2 is a novel strategy for neurovascular protection after
      ischemia/reperfusion. Our recent study identified the signal transducer and
      activator of transcription 3 (STAT3) as a transcription factor of the mouse SOD2
      gene. During reperfusion, activation of STAT3 and its recruitment into the SOD2
      gene were blocked, resulting in increased oxidative stress and neuronal
      apoptosis. In contrast, pharmacological activation of STAT3 induced SOD2
      expression, which limits ischemic neuronal death. Our studies point to
      antioxidant-based neurovascular protective strategies as potential treatments to
      expand the therapeutic window of currently approved therapies.

PMID- 20157791
TI  - Falls in spinocerebellar ataxias: Results of the EuroSCA Fall Study.
AB  - To investigate the frequency, details, and consequences of falls in patients with
      autosomal dominant spinocerebellar ataxias (SCAs) and to derive specific disease
      related risk factors that are associated with an increased fall frequency. Two
      hundred twenty-eight patients with SCA1, SCA2, SCA3, or SCA6, recruited from the
      EuroSCA natural history study, completed a fall questionnaire that assessed the
      frequency, consequences, and several details of falls in the previous 12 months.
      Relevant disease characteristics were retrieved from the EuroSCA registry. The
      database of the natural history study provided the ataxia severity scores as well
      as the number and nature of non-ataxia symptoms. Patients (73.6%) reported at
      least one fall in the preceding 12 months. There was a high rate of fall-related
      injuries (74%). Factors that were associated with a higher fall frequency
      included: disease duration, severity of ataxia, the presence of pyramidal
      symptoms, the total number of non-ataxia symptoms, and the genotype SCA3. Factors
      associated with a lower fall frequency were: the presence of extrapyramidal
      symptoms (more specifically dystonia of the lower limbs) and the genotype SCA2.
      The total number of non-ataxia symptoms and longer disease duration were
      independently associated with a higher fall frequency in a logistic regression
      analysis, while the presence of extrapyramidal symptoms was independently
      associated with a lower fall frequency. Our findings indicate that, in addition
      to more obvious factors that are associated with frequent falls, such as disease
      duration and ataxia severity, non-ataxia manifestations in SCA play a major role
      in the fall etiology of these patients.

PMID- 20157790
TI  - Pluripotency maintenance mechanism of embryonic stem cells and reprogramming.
AB  - Embryonic stem (ES) cells are derived from blastocysts and are pluripotent. This
      pluripotency has attracted the interest of numerous researchers, both to expand
      our fundamental understanding of developmental biology and also because of
      potential applications in regenerative medicine. Systems biological studies have
      demonstrated that the pivotal transcription factors form a network. There they
      activate pluripotency-associated genes, including themselves, while repressing
      the developmentally regulated genes through co-occupation with various protein
      complexes. The chromatin structure characteristic of ES cells also contributes to
      the maintenance of the network. In this review, I focus on recent advances in our
      understanding of the transcriptional network that maintains pluripotency in mouse
      ES cells.

PMID- 20157792
TI  - Three new species, Lamellodiscus tubulicornis n. sp., L. magnicornis n. sp. and
      L. parvicornis n. sp. (Monogenea: Diplectanidae) from Gymnocranius spp.
      (Lethrinidae: Monotaxinae) off New Caledonia, with the proposal of the new
      morphological group 'tubulicornis' within Lamellodiscus Johnston & Tiegs, 1922.
AB  - Three new species of Lamellodiscus are described from four (including two
      undescribed) species of Gymnocranius off New Caledonia, South Pacific. All three
      species have a similar body anatomy and morphology of the haptoral hard parts and
      are distinguished on the basis of the male copulatory organ (MCO). Lamellodiscus
      tubulicornis n. sp. (type-host: G. grandoculis; other host: Gymnocranius sp. B)
      has an MCO with a tube and horn; L. magnicornis n. sp. (type-host: G.
      grandoculis; other hosts: G. euanus, Gymnocranius sp. A and Gymnocranius sp. B)
      has an MCO with a long horn and a membrane; L. parvicornis n. sp. (type-host: G.
      euanus; other hosts: G. grandoculis and Gymnocranius sp. B) has an MCO with a
      small horn and a membrane. Lamellodiscus epsilon Yamaguti, 1968 is redescribed
      based on the type-specimens (from Monotaxis grandoculis off Hawaii).
      Lamellodiscus sp. is recorded from Gnathodentex aureolineatus off New Caledonia.
      All these five species have lamellodiscs that exhibit a unique characteristic:
      the second lamella forms an almost closed circle, in contrast to all other
      described species of Lamellodiscus in which the second lamella has the form of
      one or two crescents. Lamellodiscus spp. are usually classified in two groups,
      the 'ignoratus' and 'elegans' groups, according to the structure of the
      lamellodisc; we propose a new 'tubulicornis' group for these five species. In
      addition to their lamellodisc structure, species of the tubulicornis group are
      also characterised by their egg (elongate in contrast to tetrahedral in the two
      other groups) and their hosts (monotaxine lethrinids as opposed to mainly
      sparids). The generic diagnosis of Lamellodiscus given by Amine & Euzet (2005) is
      amended to include species with elongate eggs.

PMID- 20157793
TI  - Caligus ignotus n. sp. (Copepoda: Caligidae) parasitic on Poey's scabbardfish
      Evoxymetopon poeyi (Gunther) off Taiwan.
AB  - A new species of caligid copepod, Caligus ignotus n. sp., is described from
      Poey's scabbardfish Evoxymetopon poeyi (Gunther) (Trichiuridae) caught off the
      southeast coast of Taiwan. The parasite was found in the gill-cavity of this
      benthopelagic fish. The new species is distinguished from its congeners mainly in
      the structure of the female genital complex (shaped like a guitar) and abdomen
      (with three sections and gradually broadening from anterior to posterior). This
      is the first report of a copepod parasite from Poey's scabbardfish.

PMID- 20157794
TI  - Feather mites (Astigmata: Psoroptidia) parasitising the rock ptarmigan Lagopus
      muta (Montin) (Aves: Galliformes) in Iceland.
AB  - Four new species of feather mites are described from the Icelandic rock ptarmigan
      Lagopus muta islandorum (Faber) in Iceland. These are Metamicrolichus islandicus
      n. sp., Myialges borealis n. sp. (Epidermoptidae), Strelkoviacarus holoaspis n.
      sp. (Analgidae) and Tetraolichus lagopi n. sp. (Pterolichidae). This is the first
      report on feather mites associated with the Icelandic rock ptarmigan. Brief
      comments on the systematics and biology of corresponding feather mite genera are
      given. For two species, originally described in Pterolichus Robin, 1868
      (Pterolichidae), new combinations are proposed, i.e. Tetraolichus gaudi (Cerny,
      1971) n. comb. and T. microdiscus (Trouessart, 1887) n. comb.

PMID- 20157795
TI  - Contracaecum gibsoni n. sp. and C. overstreeti n. sp. (Nematoda: Anisakidae) from
      the Dalmatian pelican Pelecanus crispus (L.) in Greek waters: genetic and
      morphological evidence.
AB  - Two new species of Contracaecum Railliet & Henry, 1912, previously referred to as
      C. multipapillatum sp. A and C. multipapillatum sp. B by Nascetti et al. (1990)
      from the Dalmatian pelican Pelecanus crispus (L.) in the Ambracian Gulf off
      Greece, are described as C. gibsoni n. sp. and C. overstreeti n. sp.,
      respectively. Morphological analysis and the differential diagnosis of
      genetically recognised male specimens of C. gibsoni and C. overstreeti with
      respect to C. multipapillatum (von Drasche, 1882) (sensu lato) from Egretta alba
      (L.) in northern Colombia and other morphologically related Contracaecum spp.
      enabled the detection of differences between the two species in a number of
      characters, including spicule length and the shape of its tip, and the
      arrangement of the proximal and distal papillae on the male tail. Accordingly,
      formal descriptions are presented for C. gibsoni n. sp. and C. overstreeti n. sp.
      from P. crispus. The genetic characterisation of the two taxa is based on 20
      allozyme loci and sequence analyses (519 bp) of the mtDNA cox2 gene. Reproductive
      isolation was demonstrated between these two taxa, which sympatrically infect the
      same definitive host, and fixed allele differences between the two species were
      found at some (Aat-2, PepC-1, PepC-2 and Pgm-1) of the 20 allozyme loci analysed.
      Their genetic divergence, estimated at the allozyme level, was D ( Nei ) = 0.31.
      The genetic relationships of C. gibsoni and C. overstreeti with respect to C.
      multipapillatum (s. l.) collected from E. alba in Colombia, as well as with other
      congeners from fish-eating birds which had previously been genetically
      characterised using the same genetic markers, i.e. C. rudolphii A and C.
      rudolphii B of Bullini et al. (1986), C. septentrionale Kreis, 1955, C.
      microcephalum (Rudolphi, 1809), C. bioccai Mattiucci et al., 2008, C. pelagicum
      Johnston & Mawson, 1942 and C. micropapillatum (Stossich, 1890), were inferred
      from mtDNA cox2 sequence analysis. The MP, NJ and BI trees obtained were
      congruent in depicting C. gibsoni and C. overstreeti as closely related species
      but quite distinct from each other and forming a subclade with specimens of C.
      multipapilllatum (s. l.) from E. alba (L.) in Colombia. This subclade was also
      found to be distinct from the remainder of the taxa considered.

PMID- 20157796
TI  - Isospora piacobrai n. sp. (Apicomplexa: Eimeriidae) from the masked yellowthroat
      Geothlypis aequinoctialis (Gmelin) (Passeriformes: Parulidae) in South America.
AB  - A new coccidian species (Protozoa: Apicomplexa: Eimeriidae) obtained from masked
      yellowthroat Geothlypis aequinoctialis (Gmelin) is reported from Brazil. Isospora
      piacobrai n. sp. has oocysts which are subspheroidal to ovoidal, measure 15.8 x
      10.5 microm and have a smooth, bilayered wall c. 1.2 microm thick. A micropyle
      and oocyst residuum are absent, but a polar granule is present. Its sporocysts
      are ovoidal and measure 15.8 x 10.5 microm. The Stieda body is knob-like and
      prominent, the substieda body large, trapezoidal and homogeneous, and the
      sporocyst residuum composed of granules of different sizes. Sporozoites are
      vermiform with one refractile body and a nucleus. This is the first description
      of an isosporoid coccidian infecting a bird of the family Parulidae.

PMID- 20157797
TI  - Neoechinorhynchus (Neoechinorhynchus) chimalapasensis n. sp. (Acanthocephala:
      Neoechinorhynchidae) from the freshwater fish Awaous banana (Valenciennes)
      (Gobiidae) in Mexico.
AB  - Neoechinorhynchus (Neoechinorhynchus) chimalapasensis n. sp. (Eoacanthocephala:
      Neoechinorhynchidae) is described from the intestine of Awaous banana
      (Valenciennes) (Pisces: Gobiidae) collected in the Rio Negro, a tributary in the
      upper Rio Coatzacoalcos basin, Santa Maria Chimalapa, Oaxaca State, Mexico. It is
      the third species of Neoechinorhynchus Stiles & Hassall, 1905 described from
      Mexican freshwater fishes, although 36 other species are known from freshwater
      fishes in the Americas. Like four other species of Neoechinorhynchus from
      freshwater fishes in North America and Mexico, N. (N.) limi Muzzall & Buckner,
      1982, (N.) rutili (Muller, 1780) Stiles & Hassall, 1905, N. (N.) salmonis Ching,
      1984 and N. (N.) roseus Salgado-Maldonado, 1978, males and females of the new
      species are less than 20 mm in length, lack conspicuous sexual dimorphism in
      size, have a small proboscis of about 0.1 mm in length with the largest hooks
      being the anteriormost, about 30-90 microm in length and of equal size, and have
      subequal lemnisci, larger than the proboscis receptacle but still relatively
      short and, in males, generally restricted to a position considerably anterior to
      the testes. The new species is closest to N. (N.) roseus, but it is distinguished
      from it by having: (1) a slightly larger cylindrical proboscis with almost
      parallel sides versus a globular proboscis with a rounded tip which is shorter
      and somewhat wider in N. (N.) roseus; (2) smaller but robust anterior proboscis
      hooks that do not reach the equatorial level or extend beyond the hooks of the
      middle circle as in N. (N.) roseus; and (3) the female gonopore situated
      ventrally subterminal, as opposed to being a significant distance anteriorly to
      the posterior extremity in N. (N.) roseus.

PMID- 20157798
TI  - Cultural-related, contextual, and asthma-specific risks associated with asthma
      morbidity in urban children.
AB  - The objective of this study was to examine associations between specific
      dimensions of the multi-dimensional cumulative risk index (CRI) and asthma
      morbidity in urban, school-aged children from African American, Latino and Non
      Latino White backgrounds. An additional goal of the study was to identify the
      proportion of families that qualify for high-risk status on each dimension of the
      CRI by ethnic group. A total of 264 children with asthma, ages 7-15 (40% female;
      76% ethnic minority) and their primary caregivers completed interview-based
      questionnaires assessing cultural, contextual, and asthma-specific risks that can
      impact asthma morbidity. Higher levels of asthma-related risks were associated
      with more functional morbidity for all groups of children, despite ethnic group
      background. Contextual and cultural risk dimensions contributed to more morbidity
      for African-American and Latino children. Analyses by Latino ethnic subgroup
      revealed that contextual and cultural risks are significantly related to more
      functional morbidity for Puerto Rican children compared to Dominican children.
      Findings suggest which type of risks may more meaningfully contribute to
      variations in asthma morbidity for children from specific ethnic groups. These
      results can inform culturally sensitive clinical interventions for urban children
      with asthma whose health outcomes lag far behind their non-Latino White
      counterparts.

PMID- 20157799
TI  - Changes in pediatric health-related quality of life in cystic fibrosis after IV
      antibiotic treatment for pulmonary exacerbations.
AB  - Intravenous (IV) antibiotic therapy for pulmonary exacerbations (PE) has been
      shown to improve pulmonary functioning for patients with cystic fibrosis (CF);
      however, little is known about its effects on pediatric health-related quality of
      life (HRQOL). This prospective study assessed the impact of IV treatment of a PE
      on generic and CF-specific HRQOL for children and adolescents with CF.
      Participants included 52 children and adolescents with CF experiencing a PE (M
      (age) = 13.6 years; 54% males; M(FEV(1%)) predicted = 58.8%). HRQOL, pulmonary
      functioning, and body mass index were assessed before and after IV antibiotic
      treatment. Results of this prospective, observational study indicated significant
      improvements on CFQ-R Respiratory (M (change score) = 11.7; 95% CI = 6.3-17.1; p
      < .0001) and Weight (M (change score) = 15.9; 95% CI = 7.9-23.8; p < .0001)
      scales. The CF-specific measure was more sensitive to changes in HRQOL than the
      generic instrument. These data suggest that CF-specific HRQOL improves with
      treatment for a PE with IV antibiotics. The noted statistically and clinically
      significant changes in the CFQ-respiratory scale indicate that the measure may be
      beneficial to pulmonary health care teams.

PMID- 20157801
TI  - Characterization of common measures of heart period variability in healthy human
      subjects: implications for patient monitoring.
AB  - OBJECTIVE: Heart period variability has been considered for clinical assessment
      of autonomic function, determining the presence of haemorrhage or disease states,
      and for predicting mortality from traumatic injury. However, for heart period
      variability to be clinically useful, a number of important methodological issues
      should be addressed, including the minimum number of R-R intervals (RRI) required
      for accurate derivation, and the reproducibility of these metrics. METHODS: ECGs
      were recorded for > or =10 min in 18 resting, supine subjects (12 M/6 F; 19-55
      years). Heart period variability analyses included 21 time, frequency and
      complexity domain metrics. For assessment of minimum RRIs required, measurements
      were made from ECG recordings of 5 min down to 30 s for time and frequency domain
      metrics, and from 800 RRIs down to 100 RRIs for complexity metrics, by methodical
      truncation of the data set. Inter-subject variability was assessed by calculating
      the range and co-efficient of variation (%CV) across all subjects. Two
      independent 30 s or 100 RRI ECG segments were used to assess intra-subject
      variability via calculation of %CV in each subject. RESULTS: Six time and
      frequency domain metrics were robust down to 30 s of data, while five complexity
      metrics were robust down to 100 RRIs. All time and frequency domain metrics
      (except for RRI) exhibited high inter-subject variability (CVs > or = 30.0%),
      while five of eleven complexity metrics displayed low inter-subject variability
      (CVs < or = 8.5%). In the assessment of intra-subject variability in metrics
      valid with 30 s or 100 RRIs of ECG, only one time domain and four complexity
      metrics had CVs < 10%. CONCLUSIONS: Metrics that are highly reproducible and
      require few RRIs are advantageous for patient monitoring as less time is required
      to assess physiological status and initiate early interventions. Based on our
      analyses from healthy, resting humans, we have identified a select cohort of
      heart period variability metrics that performed well in regards to these two
      criteria.

PMID- 20157803
TI  - [Presurgical functional magnetic resonance imaging].
AB  - Functional magnetic resonance imaging (fMRI) is an important and novel
      neuroimaging modality for patients with brain tumors. By non-invasive
      measurement, localization and lateralization of brain activiation, most
      importantly of motor and speech function, fMRI facilitates the selection of the
      most appropriate and sparing treatment and function-preserving surgery.
      Prerequisites for the diagnostic use of fMRI are the application of dedicated
      clinical imaging protocols and standardization of the respective imaging
      procedures. The combination with diffusion tensor imaging (DTI) also enables
      tracking and visualization of important fiber bundles such as the pyramidal tract
      and the arcuate fascicle. These multimodal MR data can be implemented in computer
      systems for functional neuronavigation or radiation treatment. The
      practicability, accuracy and reliability of presurgical fMRI have been validated
      by large numbers of published data. However, fMRI cannot be considered as a fully
      established modality of diagnostic neuroimaging due to the lack of guidelines of
      the responsible medical associations as well as the lack of medical certification
      of important hardware and software components. This article reviews the current
      research in the field and provides practical information relevant for presurgical
      fMRI.

PMID- 20157805
TI  - [Core needle biopsy twice negative with rising PSA level. Does imaging help?].
AB  - In compliance with guidelines in cases of suspected prostate cancer, the standard
      approach involves transrectal ultrasound-guided systematic biopsies. Currently,
      according to the new S3 guideline for prostate cancer, 10-12 tissue samples
      should be collected per patient and session. If these primary specimens are
      negative, the number of multiple biopsies is generally increased in the second
      session to improve the diagnostic certainty with more biopsies. At the latest
      when the second core needle biopsy is performed in the presence of rising
      prostate-specific antigen (PSA) level, an attempt is made to minimize the risk of
      overlooking prostate cancer by further increasing the number of multiple biopsies
      in the sense of achieving saturation. In this instance, the number ranges from 6
      to 143 tissue samples per session. Studies have provided evidence that after two
      systematic random biopsies the same number of additional random biopsies does not
      accomplish any essential improvement of diagnostic certainty. There are hardly
      any studies in the literature dealing with the role of imaging procedures after
      negative prostate biopsies. In a prospective clinical trial including 132
      patients with an average of 12 negative previous biopsies, a dramatically high
      number of prostate carcinomas (66 of 132) could be detected with innovative
      imaging (1-6 targeted biopsies). This raises the question of how reliably
      multiple systematic biopsies can in fact exclude the presence of cancer. Thus,
      particularly after a negative series of multiple biopsies, it appears to be
      expedient to use specific imaging to enhance diagnostic certainty through
      quality. However, prospective clinical validation of the diverse innovative
      methods seems to be important before broad application.

PMID- 20157806
TI  - Validation of a 5-year risk score of hip fracture in postmenopausal women. The
      Danish Nurse Cohort Study.
AB  - SUMMARY: We evaluated the Women's Health Initiative (WHI) hip fracture risk score
      in 15,648 postmenopausal Danish nurses. The algorithm was well calibrated for
      Denmark. However, the sensitivity was poor at common decision making thresholds.
      Obtaining sensitivity better than 80% led to a low specificity of 61.4%.
      INTRODUCTION: A new score based on data from the WHI has been designed to predict
      5-year risk of hip fracture in postmenopausal women. The performance of the
      algorithm has not been validated in populations with different lifestyle
      characteristics and ethnicity. The aim of this study was to test the clinical
      performance of the algorithm in a large Danish cohort of postmenopausal Caucasian
      women against hip fracture. METHODS: The Danish Nurse Cohort is a prospective
      risk factor and hormone therapy (HT) study established in 1993. Participants in
      the present analysis were 15,648 postmenopausal nurses. The calibration and
      diagnostic performance of the WHI algorithm was evaluated using fracture events
      captured in the Danish National Hospital Registry. RESULTS: During 5 years of
      follow-up, 122 participants suffered a hip fracture (1.8/1,000 person years). The
      WHI algorithm predicted that 107 hip fractures would occur, indicating an
      underestimation of the number of fractures by 12%. To obtain sensitivity better
      than 80%, the cut-off value for 5-year risk was set to 0.5%, which was
      accompanied by a low positive predictive value of 1.9% and a low specificity of
      61.4%. The algorithm predicted too many fractures in HT-users (12 observed, 22
      expected) and too few in non HT-users (107 observed, 81 expected). CONCLUSIONS:
      While the WHI algorithm was well calibrated on the Danish population, the
      clinical utility of the WHI algorithm in Danish postmenopausal women was limited
      by poor sensitivity at common decision-making thresholds and suboptimal in non-HT
      users.

PMID- 20157807
TI  - Ciliary neurotrophic factor inhibits bone formation and plays a sex-specific role
      in bone growth and remodeling.
AB  - Ciliary neurotrophic factor (CNTF) receptor (CNTFR) expression has been described
      in osteoblast-like cells, suggesting a role for CNTF in bone metabolism. When
      bound to CNTF, neuropoietin (NP), or cardiotrophin-like-cytokine (CLC), CNTFR
      forms a signaling complex with gp130 and the leukemia inhibitory factor receptor,
      which both play critical roles in bone cell biology. This study aimed to
      determine the role of CNTFR-signaling cytokines in bone. Immunohistochemistry
      detected CNTF in osteoblasts, osteocytes, osteoclasts, and proliferating
      chondrocytes. CNTFR mRNA was detected in primary calvarial osteoblasts and was
      upregulated during osteoblast differentiation. Treatment of osteoblasts with CNTF
      or CLC, but not NP, significantly inhibited mineralization and osterix mRNA
      levels. Twelve-week-old male CNTF ( -/- ) mice demonstrated reduced femoral
      length, cortical thickness, and periosteal circumference; but femoral trabecular
      bone mineral density (Tb.BMD) and tibial trabecular bone volume (BV/TV) were not
      significantly different from wild-type, indicating a unique role for CNTF in bone
      growth in male mice. In contrast, female CNTF ( -/- ) femora were of normal
      width, but femoral Tb.BMD, tibial BV/TV, trabecular number, and trabecular
      thickness were all increased. Female CNTF ( -/- ) tibiae also demonstrated high
      osteoblast number and mineral apposition rate compared to wild-type littermates,
      and this was intrinsic to the osteoblast lineage. CNTF is expressed locally in
      bone and plays a unique role in female mice as an inhibitor of trabecular bone
      formation and in male mice as a stimulus of cortical growth.

PMID- 20157808
TI  - Construction of an engineered strain free of antibiotic resistance gene markers
      for simultaneous mineralization of methyl parathion and ortho-nitrophenol.
AB  - Pseudomonas sp. strain NyZ402, a native soil organism that grows on para
      nitrophenol (PNP), was genetically engineered for the simultaneous degradation of
      methyl parathion (MP) and ortho-nitrophenol (ONP) by integrating mph (methyl
      parathion hydrolase gene) from Pseudomonas sp. strain WBC-3 and onpAB (ONP 2
      monooxygenase and ONP o-benzoquinone reductase genes) from Alcaligenes sp. strain
      NyZ215 into the genome of strain NyZ402. Methyl parathion hydrolase (MPH), ONP 2
      monooxygenase (OnpA) and o-benzoquinone reductase (OnpB) were constitutively
      expressed in the engineered strain NyZ-MO. Strain NyZ-MO was free of exogenous
      antibiotic resistance gene markers and the introduced genes were genetically
      stable. Degradation experiments showed that strain NyZ-MO could utilize MP or ONP
      as the sole carbon and energy source, and mineralize 0.1 mM MP-0.1 mM ONP
      simultaneously. This method may serve as a useful strategy for the construction
      of engineered strains in the degradation of multiple environmental pollutants.

PMID- 20157809
TI  - Cofactor-independent oxidases and oxygenases.
AB  - Whereas the majority of O(2)-metabolizing enzymes depend on transition metal ions
      or organic cofactors for catalysis, a significant number of oxygenases and
      oxidases neither contain nor require any cofactor. Among the cofactor-independent
      oxidases, urate oxidase, coproporphyrinogen oxidase, and formylglycine-generating
      enzyme are of mechanistic as well as medical interest. Formylglycine-generating
      enzyme is also a promising tool for protein engineering as it can be used to
      equip proteins with a reactive aldehyde function. PqqC, an oxidase in the
      biosynthesis of the bacterial cofactor pyrroloquinoline quinone, catalyzes an
      eight-electron ring-closure oxidation reaction. Among bacterial oxygenases,
      quinone-forming monooxygenases involved in the tailoring of polyketides, the
      dioxygenase DpgC found in the biosynthesis of a building block of vancomycin and
      teicoplanin antibiotics, luciferase monooxygenase from Renilla sp., and bacterial
      ring-cleaving 2,4-dioxygenases active towards 3-hydroxy-4(1H)-quinolones have
      been identified as cofactor-independent enzymes. Interestingly, the 3-hydroxy
      4(1H)-quinolone 2,4-dioxygenases as well as Renilla luciferase use an alpha/beta
      hydrolase architecture for oxygenation reactions. Cofactor-independent oxygenases
      and oxidases catalyze very different reactions and belong to several different
      protein families, reflecting their diverse origin. Nevertheless, they all may
      share the common mechanistic concept of initial base-catalyzed activation of
      their organic substrate and "substrate-assisted catalysis".

PMID- 20157810
TI  - Manipulation under anaesthesia for frozen shoulder in patients with and without
      non-insulin dependent diabetes mellitus.
AB  - Manipulation under anaesthesia (MUA) has been used to speed up recovery. However,
      the outcome of frozen shoulder after MUA in patients with diabetes has not been
      well documented in the past. A higher prevalence of frozen shoulder has been
      reported in diabetes mellitus (DM) patients. In this study, we revealed the short
      and long-term outcomes for treatment of frozen shoulders by MUA and compared
      these results in patients with and without non-insulin dependent DM by adjusted
      Constant score. The scores showed no significant differences between the two
      groups at both early and late follow-ups. Our results revealed that MUA for
      frozen shoulders is a simple and noninvasive procedure to improve symptoms and
      shoulder function within a short period of time. Even though DM is a predisposing
      factor to frozen shoulder, non-insulin dependent DM alone does not influence both
      the short- and long-term outcomes of frozen shoulder.

PMID- 20157812
TI  - Mid-term results of Scarf osteotomy in hallux valgus.
AB  - We performed a retrospective study on 178 Scarf osteotomies with a mean follow-up
      of 44.9 months (range 15-83 months). Clinical rating was based on the forefoot
      score of the American Orthopaedic Foot and Ankle Society (AOFAS). Weight bearing
      X-rays were used to perform angular measurements and assess the first
      metatarsophalangeal joint (MTP 1). At follow-up the mean AOFAS score had improved
      significantly (p < 0.001), but only 55% of the feet showed a perfect realignment
      of the first ray. Patients with a hallux valgus angle exceeding 30 degrees  and
      pre-existing degenerative changes at the MTP 1 joint displayed inferior clinical
      results (p < 0.05). Nearly 20% of the patients suffered from pain at the MTP 1
      joint. This was clearly attributed to an onset or worsening of distinct
      radiographic signs of arthritis (p < 0.05) resulting in painfully decreased joint
      motion. Comparing radiographic appearance three months postoperatively and at
      follow-up, we found that radiographic criteria (hallux valgus, first
      intermetatarsal angle, hallux valgus interphalangeus, MTP 1 joint congruency,
      arthritic lesions at MTP 1) worsened with time.

PMID- 20157811
TI  - Anterior cruciate ligament reconstruction with synthetic grafts. A review of
      literature.
AB  - Anterior cruciate ligament (ACL) rupture, one of the most common knee injuries in
      sports, results in anteroposterior laxity, which often leads to an unstable knee.
      Traditional ACL reconstruction is performed with autograft; disadvantages of this
      technique are donor site morbidity and a long rehabilitation period. In the
      1980s, artificial ligaments became an attractive alternative to biological
      grafts. The initial enthusiasm surrounding their introduction stemmed from their
      lack of donor morbidity, their abundant supply and significant strength,
      immediate loading and reduced postoperative rehabilitation. Synthetic grafts made
      of different materials such as carbon fibers, polypropylene, Dacron and polyester
      have been utilised either as a prosthesis or as an augmentation for a biological
      ACL graft substitute. Nevertheless, every material presented serious drawbacks:
      cross-infections, immunological responses, breakage, debris dispersion leading to
      synovitis, chronic effusions, recurrent instability and knee osteoarthritis.
      Recently, a resurgence of interest in the use of synthetic prostheses has
      occurred and studies regarding new artificial grafts have been reported. Although
      many experimental studies have been made and much effort has been put forth,
      currently no ideal prosthesis mimicking natural human tissue has been found.

PMID- 20157813
TI  - Do large femoral heads reduce the risks of impingement in total hip arthroplasty
      with optimal and non-optimal cup positioning?
AB  - The purpose of this study was to assess whether large femoral heads (36-38 mm)
      improve the range of motion in total hip arthroplasty compared to standard (28-32
      mm) femoral heads in the presence of optimal and non-optimal cup positioning. A
      mathematical model of the hip joint was generated by using a laser scan of a
      dried cadaveric hip. The range of motion was assessed with a cup inclination and
      anteversion of reference and with non-optimal cup positions. Large femoral heads
      increased the range of motion, compared to the 28-mm femoral head, in the
      presence of a hip prosthesis correctly implanted and even more so in the presence
      of non-optimal cup positioning. However, with respect to the 32-mm femoral head,
      large femoral heads showed limited benefits both in the presence of optimal and
      non-optimal cup positioning.

PMID- 20157815
TI  - The fate of Gd and chelate following intravenous injection of gadodiamide in
      rats.
AB  - OBJECTIVE: The biodistribution of gadolinium (Gd) and chelate was studied in rats
      injected intravenously with a commercially available gadodiamide magnetic
      resonance contrast agent spiked with trace amounts of (14)C-labelled GdDTPA-BMA.
      METHODS: Biodistribution of the (14)C-labelled ligand in whole animals was
      visualised using quantitative whole-body autoradiography, and quantified in
      individual tissue samples by analysing for radioactivity using beta-counting.
      Biodistribution of Gd was measured by inductively coupled plasma atomic emission
      spectroscopy (ICP-AES) and inductively coupled plasma sector field mass
      spectrometry (ICP-SF-MS). RESULTS: The injected dose was rapidly excreted, with
      only 1.0% remaining in the body at 24 h. The radioactivity thereafter was mainly
      associated with kidney cortex, liver, lung, muscle and skin, with a similar rate
      of clearance for both ligand and Gd from these tissues. The ratio between (14)C
      labelled substance and Gd was not significantly different from that of the
      injected substance in most tissue samples up to 24 h after injection; the ratio
      then slowly decreased. CONCLUSIONS: The data clearly show that measurements of Gd
      concentration alone in tissue samples from animals injected with Gd-based
      contrast agents (GBCAs) cannot be used as a measure of Gd released from the
      ligand. To our knowledge, such measurements comparing Gd and ligand
      concentrations and distribution in tissue samples have not been published
      previously for any of the commercial GBCAs.

PMID- 20157814
TI  - New multispectral MRI data fusion technique for white matter lesion segmentation:
      method and comparison with thresholding in FLAIR images.
AB  - OBJECTIVE: Brain tissue segmentation by conventional threshold-based techniques
      may have limited accuracy and repeatability in older subjects. We present a new
      multispectral magnetic resonance (MR) image analysis approach for segmenting
      normal and abnormal brain tissue, including white matter lesions (WMLs). METHODS:
      We modulated two 1.5T MR sequences in the red/green colour space and calculated
      the tissue volumes using minimum variance quantisation. We tested it on 14
      subjects, mean age 73.3 +/- 10 years, representing the full range of WMLs and
      atrophy. We compared the results of WML segmentation with those using FLAIR
      derived thresholds, examined the effect of sampling location, WML amount and
      field inhomogeneities, and tested observer reliability and accuracy. RESULTS:
      FLAIR-derived thresholds were significantly affected by the location used to
      derive the threshold (P = 0.0004) and by WML volume (P = 0.0003), and had higher
      intra-rater variability than the multispectral technique (mean difference +/- SD:
      759 +/- 733 versus 69 +/- 326 voxels respectively). The multispectral technique
      misclassified 16 times fewer WMLs. CONCLUSION: Initial testing suggests that the
      multispectral technique is highly reproducible and accurate with the potential to
      be applied to routinely collected clinical MRI data.

PMID- 20157816
TI  - Comparison of different MRCP techniques for the depiction of biliary
      complications after liver transplantation.
AB  - OBJECTIVE: Biliary strictures after liver transplantation are common. We aimed to
      compare different magnetic resonance cholangiopancreatography (MRCP) sequences
      with regard to their diagnostic accuracy in depicting anastomotic stenoses (AST),
      ischaemic-type biliary lesions (ITBL) and cholelithiasis. METHODS: In patients
      with clinically suspected biliary obstruction after liver transplantation, MRCP
      was performed at 1.5 T using two-dimensional (2D) single-shot RARE, 2D T2
      weighted (T2w) HASTE, 2D TrueFISP and 3D T2w TSE RESTORE sequences. The presence
      and localisation of lesions were assessed for each sequence independently and all
      sequences together. Endoscopic retrograde cholangiopancreatography (ERCP) served
      as the "gold standard". RESULTS: Biliary strictures were detected with a
      sensitivity of 96% by MRCP and most accurately depicted when all sequences were
      analysed together. AST was visualised with highest sensitivity on TrueFISP and 3D
      T2w TSE sequences (79%). For ITBL highest sensitivity was found with the HASTE
      sequence (81%). Highest sensitivity for filling defects was revealed by the 3D
      T2w TSE sequence (54%). Receiver operating characteristic (ROC) curve/area under
      the curve (AUC) analysis revealed the best results for the 3D T2w TSE sequence.
      CONCLUSION: Our results underline the value of different MRCP sequence types for
      the depiction of biliary lesions. A clinical protocol consisting of different
      sequences may be helpful depending on the clinical question and the likely
      underlying abnormality.

PMID- 20157817
TI  - Liver tumour segmentation using contrast-enhanced multi-detector CT data:
      performance benchmarking of three semiautomated methods.
AB  - OBJECTIVE: Automatic tumour segmentation and volumetry is useful in cancer
      staging and treatment outcome assessment. This paper presents a performance
      benchmarking study on liver tumour segmentation for three semiautomatic
      algorithms: 2D region growing with knowledge-based constraints (A1), 2D voxel
      classification with propagational learning (A2) and Bayesian rule-based 3D region
      growing (A3). METHODS: CT data from 30 patients were studied, and 47 liver
      tumours were isolated and manually segmented by experts to obtain the reference
      standard. Four datasets with ten tumours were used for algorithm training and the
      remaining 37 tumours for testing. Three evaluation metrics, relative absolute
      volume difference (RAVD), volumetric overlap error (VOE) and average symmetric
      surface distance (ASSD), were computed based on computerised and reference
      segmentations. RESULTS: A1, A2 and A3 obtained mean/median RAVD scores of
      17.93/10.53%, 17.92/9.61% and 34.74/28.75%, mean/median VOEs of 30.47/26.79%,
      25.70/22.64% and 39.95/38.54%, and mean/median ASSDs of 2.05/1.41 mm, 1.57/1.15
      mm and 4.12/3.41 mm, respectively. For each metric, we obtained significantly
      lower values of A1 and A2 than A3 (P < 0.01), suggesting that A1 and A2
      outperformed A3. CONCLUSIONS: Compared with the reference standard, the overall
      performance of A1 and A2 is promising. Further development and validation is
      necessary before reliable tumour segmentation and volumetry can be widely used
      clinically.

PMID- 20157818
TI  - Juxta-articular myxoma of the knee in a 5-year-old boy: a case report and review
      of the literature (2009: 12b).
AB  - Juxta-articular myxoma (JAM) is a relatively rare variant of myxoma that occurs
      in the vicinity of large joints. It is composed of fibroblast-like cells that
      produce an excessive amount of glycosaminoglycans rich in hyaluronic acid. The
      peak incidence is between the 3rd and 5th decades of life. In this report we
      describe an extremely rare case of JAM in the knee of a 5-year-old child. The
      clinical presentation, radiological features and histopathologic findings are
      described, and the relevant literature is reviewed.

PMID- 20157820
TI  - Analysis of factors decreasing testis weight in MRL mice.
AB  - MRL/MpJ (MRL) mouse testes have several unique characteristics, including the
      appearance of oocytes, the occurrence of metaphase-specific apoptosis of meiotic
      spermatocytes, and the presence of heat-shock-resistant spermatocytes. In the
      present study we used chromosomal mapping to determine the genomic background
      associated with small testis size in MRL mice. We prepared and analyzed C57BL/6
      based congenic mice carrying MRL mouse loci. Quantitative trait loci (QTL)
      analysis revealed susceptibility loci for small testis size at 100 cM on
      chromosome (Chr) 1 and at around 80 cM on Chr 2. Analysis with B6.MRLc1 and
      B6.MRLc2 congenic mice and double-congenic mice confirmed the QTL data and showed
      that low testis weight in MRL mice was caused by germ cell apoptosis. Through
      histological examinations we found that B6.MRLc1 and B6.MRLc2 mice showed stage
      specific apoptosis in their testes, the former at metaphase stage XII and the
      later at pachytene stage IV. Metaphase-specific apoptosis of spermatocytes occurs
      due to mutation of the exonuclease 1 (Exo1) gene located at 100 cM on Chr 1.
      Thus, the mutation of the Exo1 gene is also responsible for low testis weight
      caused by metaphase-specific apoptosis. In conclusion, testis weight is reduced
      in MRL mice due to apoptosis of germ cells caused by mutations in loci on Chrs 1
      and 2.

PMID- 20157821
TI  - Hepatic venous outflow obstruction in paediatric liver transplantation.
AB  - INTRODUCTION: Vascular complications after orthotopic split liver transplantation
      in children result in significant post-operative complications. MATERIALS AND
      METHODS: A review of children undergoing liver transplantation from 2004 to 2006
      was undertaken. The data was obtained based on a proforma-based analysis.
      RESULTS: Seven of 106 transplants were identified to have hepatic venous outflow
      obstruction (HVOO) of whom five were males and two were females. Median age at
      transplant was 8 years (range 3 years 4 months-15 years). The median donor-to
      recipient weight ratio was 2.78 (range 0.97-6.15). ANASTOMOTIC TECHNIQUE: Hepatic
      vein-IVC in four, Hepatic vein-hepatic vein (HV-IVC) confluence in two and cavo
      hepatic in one. Ascites was the commonest post op manifestation of HVOO. Although
      Doppler USG was useful in identifying the venous outflow obstruction, venography
      confirmed the exact site of obstruction aiding in therapeutic dilatation. Three
      of seven cases had early onset (<1 month) while 4/7 had late onset (>1 month).
      5/7 underwent venography and dilatation, of whom three are well and one is
      awaiting a repeat venography and dilatation. 2/7 died without intervention and
      1/7 died in the waiting list for retransplantation. CONCLUSION: The diagnosis of
      HVOO requires a high index of suspicion, prompting early venography to manage
      HVOO successfully. Technical steps to avoid HVOO are to keep the hepatic vein
      caval anastomosis short and wide with triangulation and to avoid graft rotation
      at the hepato caval junction.

PMID- 20157822
TI  - Management of small bowel volvulus around feeding Roux-en-Y limbs.
AB  - BACKGROUND: Patients' inability to take oral nutrition calls for alternative
      feeding. In selected pediatric patients, traditional feeding tubes are not
      tolerated and jejunal feeding tubes can be obstructive. One option is a Roux-en-Y
      feeding limb. Our institution noted complications secondary to small bowel
      volvulus around this limb. Goals of this study were to review patients who
      experienced volvulus after Roux-en-Y creation, and to identify factors
      contributing to this complication. METHODS: Institutional review board approval
      was obtained for a retrospective chart review. 25 patients were identified as
      having a Roux-en-Y jejunal feeding limb. Five developed volvulus. Factors
      documented included age, time to complication, revision, and outcome. RESULTS:
      Average age at limb creation was not statistically significant between those with
      or without volvulus. Mean time to obstruction was 228 +/- 117 days post-limb
      creation. Average limb length was 18.7 +/- 7 cm in patients with volvulus, 14 +/-
      2.3 cm in patients without. 3 of 5 patients presenting with volvulus were
      discharged home after revision; two patients died. CONCLUSION: There is no
      definitive way to prevent small bowel volvulus around Roux-en-Y feeding limbs. No
      predictors of volvulus were identified. Once revised, no recurrences were
      observed. While this complication is uncommon, it has potentially catastrophic
      outcomes requiring early intervention.

PMID- 20157823
TI  - Factors associated with site requirement for glaucoma clinical trials.

PMID- 20157824
TI  - Parafoveal vision impairments and their influence on reading performance and self
      evaluated reading abilities.
AB  - BACKGROUND AND PURPOSE: Patients with homonymous hemianopic field defects (HFD)
      after postchiasmatic cerebral brain injuries often complain about impairments in
      daily life activities, particularly problems in reading, and show considerable
      reductions of vision-related quality of life (QoL). This study aimed to assess
      the relation of "objective" reading performance and self-reported "subjective"
      reading abilities; it was further investigated whether parafoveal HFD
      characteristics have an impact on both parameters. METHODS: In postchiasmatic
      lesioned subjects with HFD (n = 43), "objective" reading performance was measured
      with Radner-Reading-Charts (reading speed, reading acuity). Vision-related QoL
      was assessed by the National-Eye-Institute-Visual-Function-Questionnaire (NEI
      VFQ). Four reading-relevant NEI-VFQ items that assessed "subjective" reading
      abilities were separately analyzed. Macular sparing measures were derived from
      campimetry (+/-16 degrees vertical, +/-21.5 degrees horizontal); i.e., the
      vertical HFD border between +/-2 degrees and the proportion of intact parafoveal
      visual field within the "reading window". Since macular sparing may be a
      perimetric artefact, eye movements during campimetry were recorded in 26
      subjects. RESULTS: Mean reading speed of the total sample (90.72 +/- 33.96 words
      per minute) was considerably reduced, as was the patients' vision-related QoL,
      which was revealed by diminished NEI-VFQ scores. Reading acuity was 0.12 +/- 0.13
      LogRAD (0.81 +/- 0.26 according to the decimal system). There were significant
      but weak correlations between reading acuity and speed with all reading-relevant
      NEI-VFQ-items (r-range, reading acuity: -0.57 to -0.38, reading speed: 0.33 to
      0.43) and 7/12 NEI-VFQ-subscales (r-range, reading acuity: -0.47 to -0.33,
      reading speed: 0.31 to 0.40). The intact parafoveal visual field correlated
      significantly with 2/4 reading-related NEI-VFQ-items and with 4/12 NEI-VFQ
      subscales (r-range 0.31 to 0.52). Reading acuity and mean reading speed were both
      correlated with fixation accuracy during campimetry (r = -0.38 and 0.45).
      Correlations of spared areas between +2 degrees to -2 degrees and the relative
      and absolute defect HFD border with reading speed, but not reading acuity, tended
      to significance. Subjects deviated from the campimetric fixation mark in a SD
      range of +/-5.2 degrees vertically and +/-6.5 degrees horizontally but eye
      movement ranges were not correlated with macular sparing measures. CONCLUSIONS:
      Patients with HFD showed severely reduced reading speed, which was reflected in
      subjectively diminished reading performance, and reduced reading-related QoL
      parameters. Larger areas of functionally intact parafoveal vision were associated
      with better reading performance. Although eye movements occurred during
      campimetry, these did not seem to constitute an artificially enlarged area of
      parafoveal intact vision.

PMID- 20157825
TI  - The role of the pathologist in tissue banking: European Consensus Expert Group
      Report.
AB  - Human tissue biobanking encompasses a wide range of activities and study designs
      and is critical for application of a wide range of new technologies (-"omics") to
      the discovery of molecular patterns of disease and for implementation of novel
      biomarkers into clinical trials. Pathology is the cornerstone of hospital-based
      tissue biobanking. Pathologists not only provide essential information
      identifying the specimen but also make decisions on what should be biobanked,
      making sure that the timing of all operations is consistent with both the
      requirements of clinical diagnosis and the optimal preservation of biological
      products. This document summarizes the conclusions of a Pathology Expert Group
      Meeting within the European Biological and Biomolecular Research Infrastructure
      (BBMRI) Program. These recommendations are aimed at providing guidance for
      pathologists as well as for institutions hosting biobanks on how to better
      integrate and support pathological activities within the framework of biobanks
      that fulfill international standards.

PMID- 20157826
TI  - Decidual vascular patterns in first-trimester abortions.
AB  - In many cases of early spontaneous abortion (ESA), no reasonable etiology can be
      documented. However, some of these cases show abnormal decidual vessels that
      could be overlooked when examined on hematoxylin and eosin (H&E) slides alone.
      Diagnostic accuracy could be improved by the use of a limited histochemical (HC)
      and immunohistochemical (IHC) panel. We reviewed 1,095 ESAs, selecting 176 cases
      with abnormal decidual vessels and subclassifying them into three groups on the
      basis of decidual vascular pattern. Various HC and IHC stainings were performed
      in order to assess their use in improving diagnostic sensitivity. Histological
      findings on H&E were recorded and compared to the results obtained with HC and
      IHC. A variable role in the improvement of morphologic details was demonstrated
      for all three tested HC stainings (periodic acid-Schiff, Masson's trichrome,
      Weigert's stain for fibrin) and for two of the IHC markers (smooth muscle actin,
      human placental lactogen). In many cases of ESA, only compatibility diagnoses can
      be formulated. However, using a limited panel of HC and IHC stainings, some
      significant findings can be more reliably reported, allowing the pathologist to
      acquire confidence in his routine diagnostic work.

PMID- 20157827
TI  - Population description and its role in the interpretation of genetic association.
AB  - Despite calls for greater clarity and precision of population description,
      studies have documented persistent ambiguity in the use of race/ethnicity terms
      in genetic research. It is unclear why investigators tolerate such ambiguity, or
      what effect these practices have on the evaluation of reported associations. To
      explore the way that population description is used to replicate and/or extend
      previously reported genetic observations, we examined articles describing the
      association of the peroxisome proliferator-activated receptor-gamma-gamma
      Pro12Ala polymorphism with type 2 diabetes mellitus and related phenotypes,
      published between 1997 and 2005. The 80 articles identified were subjected to a
      detailed content analysis to determine (1) how sampled populations were
      described, (2) whether and how the choice of sample was explained, and (3) how
      the allele frequency and genetic association findings identified were
      contextualized and interpreted. In common with previous reports, we observed a
      variety of sample descriptions and little explanation for the choice of
      population investigated. Samples of European origin were typically described with
      greater specificity than samples of other origin. However, findings from European
      samples were nearly always compared to samples described as "Caucasian" and
      sometimes generalized to all Caucasians or to all humans. These findings suggest
      that care with population description, while important, may not fully address
      analytical concerns regarding the interpretation of variable study outcomes or
      ethical concerns regarding the attribution of genetic observations to broad
      social groups. Instead, criteria which help investigators better distinguish
      justified and unjustified forms of population generalization may be required.

PMID- 20157828
TI  - A genome-wide survey does not show the genetic distinctiveness of Basques.
AB  - Basques are a cultural isolate, and, according to mainly allele frequencies of
      classical polymorphisms, also a genetic isolate. We investigated the
      differentiation of Spanish Basques from the rest of Iberian populations by means
      of a dense, genome-wide SNP array. We found that F (ST) distances between Spanish
      Basques and other populations were similar to those between pairs of non-Basque
      populations. The same result is found in a PCA of individuals, showing a general
      distinction between Iberians and other South Europeans independently of being
      Basques. Pathogen-mediated natural selection may be responsible for the high
      differentiation previously reported for Basques at very specific genes such as
      ABO, RH, and HLA. Thus, Basques cannot be considered a genetic outlier under a
      general genome scope and interpretations on their origin may have to be revised.

PMID- 20157830
TI  - Hemorrhagic shock 3 days after catheterization from the axillary vein.
AB  - A 72-year-old woman presented pulmonary embolism. Continuous intravenous
      administration of heparin was controlled with values of activated clotting time
      targeted from 150 to 180 s. On the sixth intensive care unit (ICU) day, a central
      vein (CV) catheter was inserted through the right axillary vein. On the ninth ICU
      day, her blood pressure dropped and her right breast was obviously larger than
      the left. Chest computed tomography showed a large hematoma under the greater
      pectoral muscle. CV catheterization under anticoagulant therapy is risky for
      bleeding, but catheterization of the internal jugular vein rarely leads to
      hemorrhagic shock, even if it causes airway obstruction. The axillary vein is in
      a compartment filled with loose tissue. As there is no structure to cover the
      bleeding site, the hematoma would expand from the lateral region of the thorax to
      near the fifth or sixth rib, to which greater and smaller pectoral muscles are
      attached. Ultrasound-guided catheterization from the axillary vein is introduced
      as a new and promising alternative to that from the subclavian vein because of
      its safety, but we should be conservative about applying the axillary approach to
      patients with anticoagulant therapy, especially in case of an unskilled operator,
      and be aware of the possibility of late-onset bleeding.

PMID- 20157829
TI  - Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and
      further expand the clinical spectrum of holoprosencephaly.
AB  - Schizencephaly (SCH) is a clinically and etiologically heterogeneous cerebral
      malformation presenting as unilateral or bilateral hemispheric cleft with direct
      connection between the inner and outer liquor spaces. The SCH cleft is usually
      lined by gray matter, which appears polymicrogyric implying an associated
      impairment of neuronal migration. The majority of SCH patients are sporadic, but
      familial SCH has been described. An initial report of heterozygous mutations in
      the homeobox gene EMX2 could not be confirmed in 52 patients investigated in this
      study in agreement with two independent SCH patient cohorts published previously.
      SCH frequently occurs with additional cerebral malformations like hypoplasia or
      aplasia of the septum pellucidum or optic nerve, suggesting the involvement of
      genes important for the establishment of midline forebrain structures. We
      therefore considered holoprosencephaly (HPE)-associated genes as potential SCH
      candidates and report for the first time heterozygous mutations in SIX3 and SHH
      in a total of three unrelated patients and one fetus with SCH; one of them
      without obvious associated malformations of midline forebrain structures. Three
      of these mutations have previously been reported in independent patients with
      HPE. SIX3 acts directly upstream of SHH, and the SHH pathway is a key regulator
      of ventral forebrain patterning. Our data indicate that in a subset of patients
      SCH may develop as one aspect of a more complex malformation of the ventral
      forebrain, directly result from mutations in the SHH pathway and hence be
      considered as yet another feature of the broad phenotypic spectrum of
      holoprosencephaly.

PMID- 20157831
TI  - A case of paradoxical embolization and subsequent Takotsubo cardiomyopathy during
      general anesthesia.

PMID- 20157832
TI  - Involvement of the kappa-opioid receptor in nitrous oxide-induced analgesia in
      mice.
AB  - Nitrous oxide (N(2)O)-induced analgesia is thought to be mediated by endogenous
      opioids. We previously showed that the mu-opioid receptor is not required for the
      analgesic action of N(2)O in mice using a gene knockout approach. In this study,
      we examined the effect of kappa- (KOP)- or delta-opioid receptor (DOP)-selective
      antagonists on N(2)O-induced analgesia. The analgesic effect of N(2)O was
      evaluated using a writhing test. Male C57BL/6 mice aged 7-8 weeks were assigned
      to control, N(2)O, KOP agonist, and DOP agonist groups. According to the group
      assignment, mice were pretreated with a KOP antagonist, nor-binaltorphimine (nor
      BNI), a DOP antagonist, naltrindole hydrochloride (NTI), a KOP agonist U50488,
      and a DOP agonist SNC80. Mice in the control, KOP agonist, and DOP agonist groups
      were exposed to 25% oxygen/75% nitrogen for 30 min, and mice in the N(2)O group
      were exposed to 25% oxygen/75% N(2)O for 30 min. Nor-BNI [10 mg kg(-1),
      subcutaneously (s.c.)] significantly suppressed the analgesic effect of N(2)O and
      U50488. In contrast, NTI (10 mg kg(-1) s.c.) did not significantly affect the
      analgesic action of N(2)O, but almost completely inhibited the analgesic effect
      of SNC80. These results suggest that KOP plays an important role in the analgesic
      effect of N(2)O in mice.

PMID- 20157833
TI  - Comparison between ketamine and fentanyl-droperidol for rectal premedication in
      children: a randomized placebo controlled trial.
AB  - PURPOSE: A common concern of anesthesiologists is the management of children
      involved in stressful scenarios, and premedication is considered, in most
      situations, as useful to reduce the stress responses. This randomized placebo
      controlled study was designed to evaluate two premedicants, ketamine versus a
      combination of fentanyl-droperidol, rectally administered, in pediatric surgical
      outpatients. METHODS: We randomly assigned 120 children to three equal groups to
      be rectally premedicated with ketamine 10 mg kg(-1) (group K), fentanyl 5 microg
      kg(-1) + droperidol 100 microg kg(-1) (group F), or saline 0.2 ml kg(-1) (group
      P). A blinded observer scored the children's behavior, according to a four
      category behavioral scale, before premedication (time A), 45 min after
      premedication (time B), immediately before venipuncture (time C), and during the
      venipuncture (time D). Features of the premedication technique, complications,
      parents' opinions, and contraindications to hospital discharge were recorded.
      RESULTS: Patient discharge was delayed because of anesthesia side effects in 7
      cases (5.8%) and surgical problems in 9 (7.5%). Group F showed a higher rate of
      postoperative nausea and vomiting (PONV) than group K, whereas the latter had a
      higher rate of behavioral disturbances. The data showed a significant difference
      in the behavioral score between groups F and P, groups K and P, and groups F and
      K at time B, and between groups K and P at time C. The reaction score at
      venipuncture shows a significant difference between groups K and P only.
      CONCLUSION: In this study, premedication with rectal ketamine showed
      significantly better overall results in the preoperative period than
      premedication with either fentanyl-droperidol or placebo.

PMID- 20157834
TI  - Flow cytometric analysis of mitochondrial populations in HL-CMS systems of rice
      under H2O2 stress.
AB  - Cytoplasmic male sterility (CMS) has often been associated with mitochondrial
      dysfunction. In this report, the heterogeneity of mitochondria was analyzed in
      both Honglian (HL) CMS (YtA) rice seedlings and those of its corresponding
      maintainers (YtB) by flow cytometry and staining with rhodamine-123 (Rh-123).
      Both lines revealed two distinct fluorescence populations: high fluorescence
      populations (HFP) and light fluorescence populations (LFP), and a somewhat lower
      LFP/HFP ratio was detected in conjunction with the higher reactive oxygen species
      (ROS) content in YtA. In addition, use of the specific effector hydrogen peroxide
      (H2O2) demonstrated a correlation between the LFP/HFP ratio and ROS levels in
      both lines. Higher ROS content caused a more swift decrease of F(0)F(1)-ATPase
      activity and ATP contents in YtA than those in YtB, which accompanied with an
      obvious decline of the LFP/HFP ratio in YtA. Furthermore, a mitochondrial genomic
      DNA smear was detected by pulsed field gel electrophoresis. Taken together, these
      results implied that HL-CMS line rice seedlings and those of its corresponding
      maintainer have different proportion of Rh-123 staining mitochondria populations,
      which may be accounted for by ROS contents on the basis of ATPase activity and
      ATP contents.

PMID- 20157835
TI  - Evaluation of quality of life therapy for parents of children with obsessive
      compulsive disorders in Iran.
AB  - Previous research has provided evidence on the effectiveness of CBT in the
      symptomatic improvement of children with obsessive-compulsive disorders. There is
      also increasing recognition of the importance of involving parents and families
      in treatment. The aim of this study was to evaluate the short-term effectiveness
      of such an intervention that promoted family strengths [(quality of life therapy
      (QoLT)] for mothers of children with obsessive-compulsive disorders (OCD). The
      sample consisted of 40 children with OCD and their mothers, who had been referred
      to clinics in Esfahan city in Iran. Mothers were randomly allocated to an
      experimental (QoLT) and waiting list control group. Mothers participated in eight
      QoLT group sessions over 4 weeks. QoLT incorporated CBT techniques in managing
      OCD symptoms. Measures were completed pre- and post-intervention by both groups.
      Children completed the Yale-Brown obsession compulsion scale for Children, the
      Revised children's manifest anxiety scale, and the brief multidimensional
      student's life satisfaction scale; mothers completed the quality of life
      inventory (QoLI). QoLT was associated with decrease in OCD and anxiety symptoms
      and increase in children's satisfaction in the global, family and environment
      domains, as well as with increased QoLI scores in their mothers. Parenting
      interventions like QoLT can complement individual modalities such as CBT in the
      presence of family-related difficulties. This can be particularly applicable in
      countries and settings with limited resources and high stigma of child mental
      health problems.

PMID- 20157836
TI  - Non-invasive evaluation of vertebral artery blood flow in cervical spondylosis
      with and without vertigo and association with degenerative changes.
AB  - Cervical spondylosis is a common disease that results from degenerative changes
      of the cervical spine and vertigo may occur in this process. The aim of the
      present study was to assess the blood flow measurements of the vertebral artery
      (VA) using color Doppler ultrasonography (CDUS) in patients who have cervical
      spondylosis with and without vertigo. The study population included 101 patients
      with vertigo and spondylosis, 66 patients with spondylosis without vertigo, and
      62 healthy controls. A bilateral decrease in the VA blood flow velocities were
      measured in patients with cervical spondylosis. A negative correlation was found
      between the stage of cervical degenerative changes and the flow velocities in
      patients with vertigo, while this relationship was not found in patients without
      vertigo. The CDUS evaluation of the pretransverse and transverse segments of VAs
      demonstrated significantly reduced flow velocities in patients with spondylosis.
      The degenerative changes in the cervical spine seem to be related to these
      velocity changes in the subgroup of patients who are also affected with vertigo.
      The pretransverse segment of the VA provides valuable measurements as well as
      transverse segment of the VA, and it can be used as an appropriate segment for
      CDUS examination in cervical spondylosis and associated vertigo.

PMID- 20157837
TI  - A case of incidentally detected IgG4-related sclerosing disease involving
      inflammatory abdominal aortic aneurysm and autoimmune pancreatitis.
AB  - A 59-year-old asymptomatic man was incidentally found to have a periaortic mass
      and an elevated serum amylase level during his medical check-up. Additional
      findings, such as infiltration of immunoglobulin G4 (IgG4)-producing plasma cells
      in the mass lesion, elevation of serum IgG4 (1000 mg/dl), and pancreatic duct
      narrowing as evidenced on a magnetic resonance cholangiopancreatography scan,
      confirmed the diagnosis as retroperitoneal fibrosis complicated with autoimmune
      pancreatitis. The patient responded favorably to steroid treatment before the
      appearance of symptoms.

PMID- 20157838
TI  - Crossing paths: interactions between the cell death machinery and growth factor
      survival signals.
AB  - Cytokines and growth factors play a crucial role in the maintenance of
      haematopoietic homeostasis. They transduce signals that regulate the competing
      commitments of haematopoietic stem cells, quiescence or proliferation, retention
      of stem cell pluripotency or differentiation, and survival or demise. When the
      balance between these commitments and the requirements of the organisms is
      disturbed, particularly when it favours survival and proliferation, cancer may
      result. Cell death provoked by loss of growth factor signalling is regulated by
      the Bcl-2 family of apoptosis regulators, and thus survival messages transduced
      by growth factors must regulate the activity of these proteins. Many aspects of
      direct interactions between cytokine signalling and regulation of apoptosis
      remain elusive. In this review, we explore the mechanisms by which cytokines, in
      particular Interleukin-3 and granulocyte-macrophage colony-stimulating factor,
      promote cell survival and suppress apoptosis as models of how cytokine signalling
      and apoptotic pathways intersect.

PMID- 20157839
TI  - Poor response to clopidogrel: current and future options for its management.
AB  - Antiplatelet therapy is the cornerstone of treatment for patients with acute
      coronary syndromes and/or undergoing percutaneous coronary interventions (PCI).
      Clopidogrel, a thienopyridine antiplatelet agent, has been used to prevent
      vascular complication in atherothrombotic patients, to prevent stent thrombosis
      in patients undergoing PCI, and in long term prevention of cardiovascular and
      cerebrovascular events. More than 40 million patients in the world receive
      clopidogrel but unfortunately about 20% of these are either non or poor
      responders. Several methods have been used to assess clopidogrel-induced
      antiplatelet effects. However, none of these tests have been fully standardized
      or fully agreed upon to measure clopidogrel responsiveness. Nevertheless, many
      studies using different techniques, platelet agonists and definitions, showed
      that patients with a poor response to clopidogrel have an increased risk of
      death, reinfarction and stent thrombosis. The mechanisms leading to poor
      responsiveness are not fully clarified and are likely multifactorial: genetic
      factors, accelerated platelet turnover, up-regulation of the P2Y(12) pathways,
      high baseline platelet reactivity, poor compliance, under-dosing and drug-drug
      interactions. The management of these patients is very difficult, but some
      evidence showed that a strategy of higher maintenance dose or switch to different
      thienopyridine (e.g. ticlopidine or prasugrel) or use of glycoprotein IIb/IIIa
      inhibitors during PCI may be helpful to overcome poor responsiveness and improve
      the long-term clinical outcome. This paper reviews the impact of clopidogrel poor
      responsiveness on clinical outcomes, the mechanisms leading to poor effect and
      the different assays to assess it. Finally, current and future options for its
      management is discussed.

PMID- 20157840
TI  - Highlights from the II International Symposium of Thrombosis and Anticoagulation
      (ISTA), October 22-23, 2009, Sao Paulo, Brazil.

PMID- 20157841
TI  - Incidence of recurrent venous thromboembolism and of chronic thromboembolic
      pulmonary hypertension in patients after a first episode of pulmonary embolism.
AB  - After a first episode of pulmonary embolism (PE), two major problems need to be
      considered: risk of recurrence when anticoagulation is stopped, and risk of
      chronic thromboembolic pulmonary hypertension (CTPH). We followed prospectively
      consecutive patients who survived a first episode of PE, with or without deep
      vein thrombosis, to assess the incidence of venous thromboembolism (VTE)
      recurrences and of symptomatic and asymptomatic CTPH. After 3-6 months of oral
      anticoagulant therapy (OAT) patients underwent transthoracic echocardiography for
      measuring transtricuspid (rV-rA) gradient. When rV-rA gradient was >35 mmHg
      further evaluations were performed to rule in or out CTPH. During follow-up
      patients who developed persistent dyspnea were re-evaluated. In patients who
      underwent OAT withdrawal D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), and
      thrombophilia were evaluated one month after warfarin discontinuation. Overall,
      239 patients, 118 males, median age 59(16-89) years, were followed up for a
      median time of 36(9-192) months. Nine patients had rV-rA gradient >30 mmHg and
      <=35 mmHg, and one of 37 mmHg. Among patients with normal rV-rA gradient, one
      developed persistent dyspnea 55 months after the first event and CPTH was
      confirmed. Among 206 patients who stopped OAT, 23(11.2%) had VTE recurrence, 11
      PE(48%). Elevated DD and F1 + 2 levels after stopping OAT were significantly
      associated with recurrence. None of patients with recurrent VTE had elevated rV
      rA gradient. In our series the incidence of CTPH after a first episode of PE was
      0.4%. VTE recurrence and elevated DD and F1 + 2 levels seemed not to be related
      to the development of CTPH.

PMID- 20157842
TI  - Lonomia obliqua venomous secretion induces human platelet adhesion and
      aggregation.
AB  - The caterpillar Lonomia obliqua is a venomous animal that causes numerous
      accidents, especially in southern Brazil, where it is considered a public health
      problem. The clinical manifestations include several haemostatic disturbances
      that lead to a hemorrhagic syndrome. Considering that platelets play a central
      role in hemostasis, in this work we investigate the effects of L. obliqua
      venomous secretion upon blood platelets responses in vitro. Results obtained
      shows that L. obliqua venom directly induces aggregation and ATP secretion in
      human washed platelets in a dose-dependent manner. Electron microscopy studies
      clearly showed that the venomous bristle extract was also able to produce direct
      platelets shape change and adhesion as well as activation and formation of
      platelet aggregates. Differently from other enzyme inhibitors, the venom-induced
      platelet aggregation was significatively inhibited by p-bromophenacyl bromide, a
      specific inhibitor of phospholipases A2. Additional experiments with different
      pharmacological antagonists indicate that the aggregation response triggered by
      the venom active components occurs through a calcium-dependent mechanism
      involving arachidonic acid metabolite(s) of the cyclooxygenase pathway and
      activation of phosphodiesterase 3A, an enzyme that leads to the consumption of
      intracellular cAMP content. It was additionally found that L. obliqua-induced
      platelet aggregation was independent of ADP release. Altogether, these findings
      are in line with the need for a better understanding of the complex hemorrhagic
      syndrome resulting from the envenomation caused by L. obliqua caterpillars, and
      can also give new insights into the management of its clinical profile.

PMID- 20157843
TI  - Warfarin after anterior myocardial infarction in current era of dual antiplatelet
      therapy: a randomized feasibility trial.
AB  - In the current era of early revascularization and routine use of dual
      antiplatelet therapy, the incremental benefit of warfarin to reduce the incidence
      of left ventricular thrombus (LVT) in patients with impaired left ventricular
      ejection fraction post anterior ST-elevation myocardial infarction (aSTEMI),
      remains uncertain. The purpose of this study is to assess the feasibility of
      evaluating the added benefit and safety of triple therapy (TT-warfarin, ASA, and
      clopidogrel) versus dual therapy (DT-ASA and clopidogrel) in patients at risk of
      LVT post aSTEMI. DESIGN: Open-label randomized controlled trial. INCLUSION:
      aSTEMI, ejection fraction <40%, and no evidence of LVT. EXCLUSION:
      contraindication to, or alternate indication for anticoagulation. INTERVENTION:
      TT versus DT. FOLLOW-UP: pre-discharge and 3 month echocardiogram. OUTCOMES:
      composite of death, MI, stroke, systemic embolizarion, LVT or major bleeding at
      three months. 295 patients with aSTEMI were screened: 27% of patients with LVEF <
      40% had an LVT; 20/52 eligible patients were randomized to receive TT (n = 10) or
      DT (n = 10). Baseline characteristics: mean age 60 years, male gender 65%,
      diabetics 20%, and in hospital PCI 95%. There was no significant difference in
      the composite endpoint at 3 months (TT-20% with 1 LVT and 1 major bleed versus DT
      10% with 1 MI). The incidence of definite or probable LVT in the screened
      population of patients post aSTEMI with an LVEF < 40% was 26.6% despite 94%
      having early revascularization. STEMI patients have a high incidence of LVT
      despite the routine use of early revascularization and dual antiplatelet therapy.
      More effective antithrombotic strategies merit evaluation in adequately powered
      randomized trials.

PMID- 20157844
TI  - Relationship between proteinuria and venous thromboembolism.
AB  - Nephrotic syndrome is known to cause venous thromboembolism (VTE) due to urine
      loss of antithrombin III and activation of the coagulation system. We
      hypothesized that the degree of proteinuria may predict the development of VTE.
      This was a retrospective case-controlled study of in-patients urban academic
      teaching hospital from April, 2007 to March, 2009 and who had undergone an
      imaging study for VTE. All radiology reports (N = 1,647) for CT angiography of
      chest and Doppler sonogram of extremities were reviewed. The following data were
      collected: race/ethnicity, degree of proteinuria on urinalysis, serum protein and
      albumin levels, risk factors for VTE and renal function. The study population
      consisted of 284 patients with VTE and 280 age/sex matched controls. Relative to
      those who did not have proteinuria, patients who tested positive for protein had
      a 3.4-fold increased risk of VTE (odds ratio (OR) 3.4, 95% confidence interval
      [2.4, 5.0]). The association was unchanged when adjusted for other risk factors.
      Patients with proteinuria may have an increased risk of venous thromboembolism.

PMID- 20157845
TI  - Can incentives undermine intrinsic motivation to participate in epidemiologic
      surveys?
AB  - Response rates to surveys are decreasing. The purpose of this study was to
      evaluate the use of lottery tickets as incentives in an epidemiologic control
      group. A self-administered questionnaire was sent to parents in the municipality
      of Stockholm, Sweden, who were to be used as a control group in a study
      addressing stress in parents of children with cancer. A stratified random sample
      of 450 parents were randomized into three incentive groups: (a) no incentive; (b)
      a promised incentive of one lottery ticket to be received upon reply; (c) a
      promised incentive of one lottery ticket to be received upon reply and an
      additional lottery ticket upon reply within 1 week. The overall response rate
      across the three groups was 65.3%. The response rate was highest in the no
      incentive group (69.3%) and lowest in the one plus one lottery ticket group
      (62.0%). In a survival analysis, the difference between the two response curves
      was significant by the log-rank test (P = 0.04), with the no incentive group
      having a shorter time to response than the incentive group. Our findings suggest
      that the use of lottery tickets as incentives to increase participation in a mail
      questionnaire among parents may be less valuable or even harmful. Incentives may
      undermine motivation in studies in which the intrinsic motivation of the
      respondents is already high.

PMID- 20157847
TI  - Missouri workshop on methods for life history data analysis.

PMID- 20157846
TI  - Immunoglobulin G from breast cancer patients in stage I stimulates muscarinic
      acetylcholine receptors in MCF7 cells and induces proliferation. Participation of
      nitric oxide synthase-derived nitric oxide.
AB  - INTRODUCTION: Muscarinic acetylcholine receptors (mAChR) belong to the G-protein
      coupled receptor family and are extensively expressed in most cells in mammals.
      We had reported the expression of mAChR in murine and human breast tumors.
      METHODS: The presence of antibodies in the sera of patients with different tumors
      directed against self-proteins has been recently described. In this work, we
      investigated the presence of autoantibodies against mAChR in the sera of breast
      cancer patients in stage I (T1N0Mx-IgG). IgG purification was performed by
      affinity chromatography in protein G-agarose. We also studied the ability of
      these antibodies to modulate the proliferation of MCF-7 breast tumor cells by the
      MTS colorimetric assay. The ability of T1N0Mx-IgG to stimulate muscarinic
      signaling pathway via nitric oxide synthase was tested by Griess reaction.
      RESULTS: We demonstrated M(3) and M(4) receptors expression in MCF-7 cells.
      T1N0Mx-IgG promotes cell proliferation, mimicking the action of the muscarinic
      agonist carbachol. This effect was preferentially due to M(3) receptor activation
      in tumor cells via phospholipase C-induced nitric oxide liberation by calcium
      dependent nitric oxide synthases. IgG from control patients was unable to produce
      this effect. DISCUSSION: IgG from patients with breast cancer in early stages
      could be promoting tumor progression by muscarinic activation, and its presence
      could be determining the prognosis of this illness.

PMID- 20157848
TI  - Misclassification of current status data.
AB  - We describe a simple method for nonparametric estimation of a distribution
      function based on current status data where observations of current status
      information are subject to misclassification. Nonparametric maximum likelihood
      techniques lead to use of a straightforward set of adjustments to the familiar
      pool-adjacent-violators estimator used when misclassification is assumed absent.
      The methods consider alternative misclassification models and are extended to
      regression models for the underlying survival time. The ideas are motivated by
      and applied to an example on human papilloma virus (HPV) infection status of a
      sample of women examined in San Francisco.

PMID- 20157849
TI  - Improving care of upper respiratory infections among Latino Early Head Start
      parents.
AB  - Misconceptions about upper respiratory infections (URI) and their treatment are
      widely held, especially among Latino parents, and are associated with increased
      health care visits. The Centers for Disease Control and Prevention recommends
      community based interventions to educate families about URI. We designed a
      community-based, culturally competent health literacy intervention regarding URI,
      which was pilot tested with Latino Early Head Start (EHS) parents. In depth
      interviews were conducted to understand parents' perceptions. A paired-sample
      Wilcoxon signed rank test was used to assess change in pre-post
      knowledge/attitudes scores. Changes in care practices are described. Parents were
      very positive about this education, were open to non-antibiotic URI care, and
      reported that materials were helpful. Following the intervention, the mean
      composite knowledge/attitude score increased from 4.1 (total: 10) to 6.6 (P <
      .05). Families also reported improved care practices. EHS sites are promising
      locations for health literacy interventions regarding URI.

PMID- 20157851
TI  - HIV/STI risk among male Mexican immigrants in Dallas, Texas: findings from a
      pilot study.
AB  - Rates of HIV and STIs are higher among Latinos than the general U.S. population.
      A number of factors place Latino immigrants at particularly high risk. 128 male
      Mexican immigrants in Dallas, Texas completed personal interviews. We measured
      the prevalence of HIV/STI risk factors and identified sociodemographic and
      behavioral characteristics associated with higher risk. 9% of the total sample
      had 3 or more sexual partners in the past year. 5% had sex with a commercial sex
      worker (CSW). 11% had sex with another man. 11% had a previous STI diagnosis.
      Risk behaviors and STI history were more prevalent among men who had used illegal
      drugs or frequently consumed alcohol (18% of the sample) than among others. The
      overall prevalence of HIV/STI risk factors in this population was moderate.
      However, men who drank alcohol frequently and used illegal drugs were more likely
      than others to report engaging in behaviors that put them at risk for acquiring
      HIV/STI.

PMID- 20157850
TI  - Impact of socio-demographic factors on HIV testing among African immigrants in
      Portugal.
AB  - This study aimed to describe the proportion of HIV testing among an African
      immigrant population in Portugal and identify the socio-demographic factors that
      may be associated. A questionnaire was applied to 522 African immigrants (53%
      men) who attend the National Immigrant Support Centre, in Lisbon. Odds ratios
      (OR) with corresponding 95% confidence intervals (95% CI) were calculated through
      logistic regression to analyse the relationships between HIV testing and other
      variables. Around 52% of participants reported having been HIV tested, mostly
      women. After adjusting for potential confounders, age and educational level were
      significantly associated with HIV testing for both women and men. Searching for
      HIV information at NHS was also significantly associated with HIV testing, but
      only among men. This study points out interesting challenges for HIV prevention
      programs among African immigrants and may help in the development of tailored
      projects focused on the promotion of HIV testing among these populations.

PMID- 20157852
TI  - Differential effects of ecstasy on short-term and working memory: a meta
      analysis.
AB  - Quantitative analysis of studies examining the effect of ecstasy on short-term
      and working memory in the verbal and visuo-spatial domain was undertaken. Thirty
      verbal short-term memory, 22 verbal working memory, 12 visuospatial short-term
      memory and 9 visuospatial working memory studies met inclusion criteria. Ecstasy
      users performed significantly worse in all memory domains, both in studies using
      drug-naive controls and studies using polydrug controls. These results are
      consistent with previous meta-analytic findings that ecstasy use is associated
      with impaired short-term memory function. Lifetime ecstasy consumption predicted
      effect size in working memory but not in short-term memory. The current meta
      analysis adds to the literature by showing that ecstasy use in humans is also
      associated with impaired working memory, and that this impairment is related to
      total lifetime ecstasy consumption. These findings highlight the long-term,
      cumulative behavioral consequences associated with ecstasy use in humans.

PMID- 20157853
TI  - Jensen's inequality as a tool for explaining the effect of oscillations on the
      average cytosolic calcium concentration.
AB  - It has often been asked which physiological advantages calcium (Ca(2+))
      oscillations in non-excitable cells may have as compared to an adjustable
      stationary Ca(2+) signal. One of the proposed answers is that an oscillatory
      regime allows a lowering of the average Ca(2+) concentration, which is likely to
      be advantageous because Ca(2+) is harmful to the cell in high concentrations. To
      check this hypothesis, we apply Jensen's inequality to study the relation between
      the average Ca(2+) concentration during oscillations and the Ca(2+) concentration
      at the (unstable) steady state. Jensen's inequality states that for a (strictly)
      convex function, the function value of the average of a set of argument values is
      lower than the average of the function values of the arguments from that set. We
      show that the kinetics of the Ca(2+) efflux out of the cell is crucial in this
      context. By analytical calculations we derive that, if the Ca(2+) efflux is a
      convex function of the cytosolic Ca(2+) concentration, then oscillations lower
      the average Ca(2+) concentration in comparison to the unstable steady state. If
      it is a concave function, the average Ca(2+) concentration is increased, while it
      remains the same if that function is linear. We also analyse the case where the
      efflux obeys a Hill kinetics, which involves both a convex and a concave part.
      The results are illustrated by numerical simulations and simple example models.
      The theoretical predictions are tested with three experimental data sets from the
      literature. In two of them, the average appears to be higher than the steady
      state value, while the third points to approximate equality. Thus oscillations
      may be used in real cells to tune the average Ca(2+) concentration in both
      directions.

PMID- 20157855
TI  - Prevention of fall-related injuries: a clinical research agenda 2009-2014.

PMID- 20157854
TI  - Abnormal interaction of motor neuropathy-associated mutant HspB8 (Hsp22) forms
      with the RNA helicase Ddx20 (gemin3).
AB  - A number of missense mutations in the two related small heat shock proteins HspB8
      (Hsp22) and HspB1 (Hsp27) have been associated with the inherited motor neuron
      diseases (MND) distal hereditary motor neuropathy and Charcot-Marie-Tooth
      disease. HspB8 and HspB1 interact with each other, suggesting that these two
      etiologic factors may act through a common biochemical mechanism. However, their
      role in neuron biology and in MND is not understood. In a yeast two-hybrid
      screen, we identified the DEAD box protein Ddx20 (gemin3, DP103) as interacting
      partner of HspB8. Using co-immunoprecipitation, chemical cross-linking, and in
      vivo quantitative fluorescence resonance energy transfer, we confirmed this
      interaction. We also show that the two disease-associated mutant HspB8 forms have
      abnormally increased binding to Ddx20. Ddx20 itself binds to the survival-of
      motor-neurons protein (SMN protein), and mutations in the SMN1 gene cause spinal
      muscular atrophy, another MND and one of the most prevalent genetic causes of
      infant mortality. Thus, these protein interaction data have linked the three
      etiologic factors HspB8, HspB1, and SMN protein, and mutations in any of their
      genes cause the various forms of MND. Ddx20 and SMN protein are involved in
      spliceosome assembly and pre-mRNA processing. RNase treatment affected the
      interaction of the mutant HspB8 with Ddx20 suggesting RNA involvement in this
      interaction and a potential role of HspB8 in ribonucleoprotein processing.

PMID- 20157856
TI  - Characteristics of Veterans Health Administration chiropractors and chiropractic
      clinics.
AB  - Chiropractic services have been delivered on station at select Veterans Health
      Administration (VHA) medical facilities since late 2004. No published data
      describing the characteristics of VHA chiropractic physicians (chiropractors) and
      chiropractic clinics exist at a national level. This study was designed to
      examine elements of the structures of chiropractic services in VHA settings. Web
      based survey methods were used to question all chiropractors in VHA facilities (N
      = 36). Data were obtained from 33 providers, yielding a 91.6% response rate. Most
      respondents were full-time VHA employees, while others were part-time employees
      or contractors. Differences were found in prior training, integrated practice,
      and academic or research experience. Of the respondents, 88% ranked low back pain
      as the most common patient complaint seen in practice and 79% ranked cervical
      pain the second most common complaint. Of the new patient consultations, 67.6%
      originated from primary care, 9.4% from pain management, and 6.2% from physiatry.
      Most respondents were similar in their reported use of diagnostic and therapeutic
      procedures, but their reported rates of participation in various facility
      activities were different. Further work is needed for researchers and policy
      makers to more fully understand the integration and delivery of chiropractic
      services in VHA settings.

PMID- 20157857
TI  - Description of outpatient utilization and costs in group of veterans with
      traumatic brain injury.
AB  - In an attempt to increase understanding regarding the nonacute healthcare needs
      of veterans with traumatic brain injury (TBI), we examined the outpatient
      utilization and cost patterns of 72 patients with TBI who were at least 4 years
      postinjury. We selected participants from a clinical database of veterans
      receiving care at a western Department of Veterans Affairs (VA) medical center.
      We extracted data from national utilization databases maintained by the VA and
      examined data from primary care and internal medicine, psychiatry and substance
      use, rehabilitation, and other services (e.g., ancillary, diagnostic, prosthetic,
      dental, nursing home, and home care). We extracted data for fiscal years 2002 to
      2007. In addition to descriptive statistics, we modeled visits per year as a
      function of time since injury. The data show that this sample of patients with
      TBI consistently used a wide array of outpatient services over time with
      considerable variation in cost. Further study regarding economic aspects of care
      for patients with TBI is warranted.

PMID- 20157858
TI  - Crossed four-bar mechanism for improved prosthetic grasp.
AB  - Passive linkages were developed to improve grasp functionality and minimize a
      prosthetic terminal device's number of user-controlled inputs. The linkages act
      to stabilize grasped objects and substitute for the palp of normal anatomical
      fingers. The Southampton Hand Assessment Procedure was used to compare the normal
      anatomical hand, this prototype, and a commercially available (Hosmer) hook. In
      testing, prosthetic terminal devices took three times as long as the normal
      anatomical hand to perform tasks. Nevertheless, heavyweight power and spherical
      grasps were improved with the use of the new mechanism compared with the
      commercial hook. Conversely, precision grasps were worsened because of the lack
      of a high-friction surface on the distal end of the prototype.

PMID- 20157859
TI  - Vibrotactile identification of signal-processed sounds from environmental events.
AB  - This study compared three different signal-processing principles (eight basic
      algorithms)-transposing, modulating, and filtering-to find the
      principle(s)/algorithm(s) that resulted in the best tactile identification of
      environmental sounds. The subjects were 19 volunteers (9 female/10 male) who were
      between 18 and 50 years old and profoundly hearing impaired. We processed sounds
      produced by 45 representative environmental events with the different algorithms
      and presented them to subjects as tactile stimuli using a wide-band stationary
      vibrator. We compared eight algorithms based on the three principles (one
      unprocessed, as reference). The subjects identified the stimuli by choosing among
      10 alternatives drawn from the 45 events. We found that algorithm and subject
      were significant factors affecting the results (repeated measures analysis of
      variance, p < 0.001). We also found large differences between individuals
      regarding which algorithm was best. The test-retest variability was small (mean
      +/- 95% confidence interval = 8 +/- 3 percentage units), and no correlation was
      noted between identification score and individual vibratory thresholds. One
      transposing algorithm and two modulating algorithms led to significantly better
      results than did the unprocessed signals (p < 0.05). Thus, the two principles of
      transposing and modulating were appropriate, whereas filtering was unsuccessful.
      In future work, the two transposing algorithms and the modulating algorithm will
      be used in tests with a portable vibrator for people with dual sensory impairment
      (hearing and vision).

PMID- 20157860
TI  - Influence of neurological level of injury in bones, muscles, and fat in
      paraplegia.
AB  - To investigate the influence of the neurological level of injury in bone mineral
      content (BMC) and mechanical properties, lean mass (LM), and fat mass (FM) among
      paraplegics with a similar duration of paralysis (DOP), we separated 30
      paraplegics into group A (15 men, high-level paraplegia) and group B (15 men, low
      level paraplegia) and compared them with group C (33 men, nondisabled). In all
      subjects, we measured stress-strain index (SSI) at 14% (SSI(2)) and 38% (SSI(3))
      of the tibia length and the difference between them using peripheral quantitative
      computed tomography (XCT 3000 [Stratec Medizintechnik, Pforzheim, Germany]) and
      lower-limb BMC, LM, and FM (g) using whole-body dual-energy X-ray absorptiometry
      (Norland XR-36 [Norland Medical Systems, Inc; Fort Atkinson, Wisconsin]). Bone
      strength parameters, BMC, and LM were statistically decreased, but we found no
      difference in paraplegic FM compared with group C. We found a correlation between
      the DOP and the difference between SSI 3 and SSI 2 in group B (r = 0.53, p = 0.03
      and r = 0.5, p = 0.04, respectively). We correlated DOP with FM in group A's
      lower limbs (r = 0.5, p = 0.05). Because of the nonsignificant DOP, the groups
      with paraplegia act differently in tibia mechanical properties and lower-limb
      body composition.

PMID- 20157861
TI  - Age-associated striatal dopaminergic denervation and falls in community-dwelling
      subjects.
AB  - Older adults have a high prevalence of gait and balance disturbances and falls.
      Normal aging is associated with significant striatal dopaminergic denervation,
      which might be a previously unrecognized additional contributor to geriatric
      falls. This study investigated the relationship between the severity of age
      associated striatal dopaminergic denervation (AASDD) and falls in community
      dwelling subjects. Community-dwelling subjects who did not have a clinical
      diagnosis to explain falls (n = 77: 43 female, 34 male; mean age 61.4 +/- 16.4;
      range 20-85) completed clinical assessment and brain dopamine transporter (DAT)
      [(11)C]beta-CFT (2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) positron
      emission tomography imaging followed by 6 months of prospective fall monitoring
      using diaries. Results showed a significant inverse relationship between striatal
      DAT activity and age (r = -0.82, p < 0.001). A total of 26 subjects (33.8%)
      reported at least one fall, with 5 subjects (6.5%) reporting two or more falls.
      While no significant difference was noted in striatal DAT activity between
      nonfallers (n = 51) and fallers (n = 26; f = 0.02, not significant), striatal DAT
      activity was modestly reduced in the small subgroup of recurrent fallers compared
      with the other subjects (f = 5.07, p < 0.05). Findings indicate that AASDD does
      not explain isolated self-reported falls in community-dwelling subjects. However,
      it may be a contributing factor in the small subgroup of subjects with recurrent
      falls.

PMID- 20157862
TI  - Insight and treatment outcome with cognitive-behavioral social skills training
      for older people with schizophrenia.
AB  - Poor insight (awareness of having a mental illness that requires treatment) is
      common in schizophrenia and typically predicts poor outcome, yet greater insight
      has been linked to negative outcomes, including hopelessness. This study focused
      on two questions: (1) Does insight moderate the effects of cognitive-behavioral
      social skills training (CBSST) on functional outcomes in schizophrenia? (2) Does
      a specific type of insight (e.g., awareness of illness, need for treatment)
      predict benefit from CBSST? We examined insight as a predictor of everyday
      functioning in a randomized controlled trial of CBSST versus treatment as usual
      (TAU) for middle-aged and older people with schizophrenia (n = 62). We used
      linear regression models to examine moderators of the relationship between
      baseline insight and everyday functioning measured 12 months following completion
      of the 6-month intervention. Insight, especially insight into the need for
      treatment, moderated the relationship between treatment group and everyday
      functioning (Independent Living Skills Survey), such that CBSST offset the
      negative effect of insight on functioning observed with TAU (wherein greater
      insight was related to poorer everyday functioning). Post hoc analyses showed
      that reduction of insight-linked hopelessness may have accounted for the positive
      effect of CBSST on functioning relative to TAU.

PMID- 20157863
TI  - Analyzing performance with computer access technology using unconstrained text
      entry protocol.
AB  - Recent work in human-computer interaction has demonstrated the use of
      unconstrained text entry protocols, which provide a more natural environment for
      research participants. We demonstrate the application of this approach to the
      analysis of word completion. Eleven participants (five nondisabled and six with
      disabilities) were recruited and asked to transcribe sentences using an on-screen
      keyboard both with and without word completion while time-stamped keystroke data
      were collected. The subsequent analysis demonstrates how the entire input stream
      (including erroneous keystrokes and the keystrokes used to correct errors) can be
      included in evaluation of performance with a text entry device or keystroke
      reduction method. Three new measures of keystroke savings are introduced, and the
      application of these measures is demonstrated.

PMID- 20157866
TI  - Title page - intrahepatic umbilical vein varix with postnatal complication in the
      newborn.

PMID- 20157867
TI  - Real-time ultrasound (US) and contrast-enhanced US for suspicious axillary lymph
      nodes in breast cancer - a love and hate relationship?

PMID- 20157868
TI  - Sonography of the pleura.

PMID- 20157869
TI  - Prevalence and risk factors of focal sparing in hepatic steatosis.
AB  - PURPOSE: The prevalence, localization and potential risk factors for focal
      sparing were prospectively assessed in subjects with sonographically detectable
      hepatic steatosis as part of a population-based cross-sectional study. MATERIALS
      AND METHODS: A total of 1,624 persons (n = 906 women; n = 718 men) were evaluated
      using ultrasonography, laboratory testing and a standardized questionnaire. The
      following were excluded from the analysis: subjects with reported alcohol
      consumption > 40 g/day (males) or > 20 g/day (females), those with known chronic
      hepatitis B or C infection, elevated serum transaminases (AST: m > 44 U/l, f > 33
      U/l; ALT: m > 45 U/l, f > 35 U/l) and prior right nephrectomy. RESULTS: The
      prevalence of focal sparing in patients with hepatic steatosis (grade I) was 25.6
      % for men and 13.0 % for women. In patients with grade II/III disease, the
      prevalence was 70.9 % for men and 77.6 % for women. The most common site of focal
      sparing was in segment IV. The average diameter was 22.3 mm (range 7 - 84 mm). No
      correlation was found for postulated risk "age" (p = 0.09) or "status post
      cholecystectomy" (p = 0.09). Male sex (p = 0.02) and metabolic syndrome (odds
      ratio, 2.1; 95 % confidence interval, 1.1 - 4.1; p = 0.02) were confirmed as risk
      factors. CONCLUSION: Sonographic evidence of focal sparing in subjects with
      hepatic steatosis is associated with an increased risk for metabolic syndrome and
      may be an easily obtained diagnostic criterion in routine clinical settings.

PMID- 20157870
TI  - Soccer endurance development in professionals.
AB  - The development of intermittent endurance capacity, its underlying mechanisms and
      role in reaching professional level in soccer was investigated. The sample
      included 130 talented youth soccer players aged 14-18, who became professional (n
      = 53) or non-professional (n = 77) players in adulthood. In total 229 Interval
      Shuttle Run Test (ISRT) scores were taken over five years. Players who became
      professionals improved from age 14 to 18 on average from 68 to 109 runs in
      contrast to players who remained amateurs (from 73 to 93 runs). A longitudinal
      model was developed using linear mixed models procedures. Intermittent endurance
      capacity can be predicted adequately with a two-level hierarchical model (p <
      0.05). Anthropometric characteristics and playing position did not improve model
      fit (p > 0.05). The estimated ISRT score necessary to reach professional level
      is: ISRT=-375.77-62.89+(51.20+4.20)* age-1.50* age (2)+3.54* hours of soccer
      training+1.18* additional training hours. In conclusion, intermittent endurance
      capacity improves with age in talented youth soccer players. From age 15 players
      who reached the professional level show a faster development than their non
      professional counterparts. This development is positively influenced by both
      soccer specific and additional training.

PMID- 20157871
TI  - Match-to-match variability of high-speed activities in premier league soccer.
AB  - The aim of the present investigation was to determine the between-match
      variability of high-speed running activities completed by a large sample of elite
      players over an extended period of time. A further aim of the study was to
      determine the influence of playing position on the magnitude of this variability.
      Observations on individual match performance measures were undertaken on 485
      outfield players (median of 10 games per player; range=2-57) competing in the
      English Premier League from 2003/2004 to 2005/2006 using a computerised tracking
      system (Prozone, Leeds, England). High-speed activities selected for analysis
      included total high-speed running distance (THSR), high-speed running (HSR),
      total sprint distance (TSD) and the total number of sprints undertaken. Total
      high-speed running distance in possession and without possession of the ball was
      also analysed. Match-to-match variability was generally high across all variables
      with a mean CV of 16.2+/-6.4% (95% CI=15.6-16.7%) and 30.8+/-11.2% (95% CI=29.9
      31.7%) reported for HSR and TSD covered during a game. This variability was
      generally higher for central players (midfielders and defenders) and lower for
      wide midfielders and attackers. Greater variability was also noted when the team
      were in possession of the ball (approximately 30%) than when they did not have
      possession (approximately 23%). The findings of the present study indicate that
      match-to-match variability in performance characteristics of elite soccer players
      is high. This inherent variability means that research requires large sample
      sizes in order to detect real systematic changes in performance characteristics.

PMID- 20157872
TI  - The use of the functional H:Q ratio to assess fatigue in soccer.
AB  - The aim of this study was to investigate the effects of fatigue induced by a
      field test representative of soccer specific movements on different
      hamstrings:quadriceps ratios in the dominant and non-dominant legs at two
      different velocities. Eight male football players (age: 21.3+/-2.3 years; height:
      178+/-8 cm; body mass: 78+/-9 kg; playing level: British University Southern
      conference-3B) performed a pre-test to assess the concentric and eccentric
      strength of the hamstrings and the quadriceps at 60 degrees x s(-1) and 180
      degrees x s(-1), The Loughborough Intermittent Shuttle Test (LIST) to simulate
      soccer, and a post-test similar to the pre-test. The main findings demonstrated
      significant decreases in the H(con):Q(con) ratio (calculated as the maximal
      concentric hamstrings strength divided by the maximal concentric quadriceps
      strength) in the dominant leg at 180 degrees x s(-1) and in the functional ratio
      H(ecc):Q(con) (calculated as the maximal eccentric hamstrings strength divided by
      the maximal concentric quadriceps strength) in the dominant leg at 60 degrees x
      s(-1) and 180 degrees x s(-1). In addition, significant correlations were
      observed between physiological parameters measured during the soccer-specific
      exercise and H(ecc):Q(con) only. These results suggested that the functional
      H(ecc):Q(con) ratio is more representative of fatigue induced by soccer than the
      conventional H(con):Q(con) ratio. Eccentric strength training at high velocities
      may be necessary to reduce injury risk in soccer players.

PMID- 20157873
TI  - Deltoid muscle characteristics in wrestlers.
AB  - The purpose of the present study was to investigate the deltoid muscle
      characteristics of wrestlers. Nine Greco-Roman competitive male wrestlers (mean
      age 20.1+/-2.7 yrs, height 175+/-0.6 cm, weight 83.2+/-12.5 kg, years of training
      7.6+/-2.7 yrs) participated in this study. Six male healthy sedentary students
      (mean age 21.2+/-0.9 yrs, height 180+/-0.3 cm, weight 80.1+/-9.4 kg) served as
      controls. Muscle fibre distribution, cross-sectional area (CSA), as well as
      satellite cells, myonuclei and capillary density per muscle fibre area were
      determined by immunohistochemistry. Myosin heavy chain MHC isoform composition of
      single fibres was determined with protein electrophoresis. Immunohistochemical
      analysis showed that muscle fibre distribution of the MHC I and IIA were
      significantly higher in wrestlers than in controls (p<0.05). Electrophoretic
      analysis of single fibres revealed a significantly higher proportion of fibres
      containing MHC I and IIC in wrestlers (p<0.05). The mean CSA of type IIA fibres
      and the number of myonuclei per type II was significantly higher in wrestlers
      (p<0.05). We also found that the number of satellite cells was 2.5 fold higher in
      wrestlers than in the control group. This study suggests that the observed muscle
      fibre profile in the deltoid of wrestlers may represent an adaptation based on
      the specific mechanical and biochemical demands of the long-term training in
      Greco-Roman wrestling.

PMID- 20157874
TI  - CK-MM gene polymorphism does not influence the blood CK activity levels after
      exhaustive eccentric exercise.
AB  - Gene variants, such as creatine kinase (CK) polymorphisms, have been suggested to
      explain the inter-individual blood CK response to eccentric exercise. However,
      since this association is still doubtful, the purpose of this study was to
      analyse the relationship between the magnitudes of the CK response to exercise
      with the occurrence of muscle CK-MM NcoI polymorphism in young healthy subjects.
      Blood CK activity was assessed in 70 subjects immediately before and 3, 24, 48,
      72, 96, 120, 168 h after strenuous eccentric exercise. Based on the amount of CK
      release by each subject, the sample was distributed in quartiles and the genotype
      and allele frequency distribution was compared among quartiles. Despite the inter
      individual variability of CK response observed between subjects, there were no
      differences in genotype and allele frequencies among quartiles. The results
      allowed us to conclude that CK response after exhaustive eccentric exercise is
      not associated with CK-MM Ncol polymorphism.

PMID- 20157875
TI  - Oxygen uptake to work rate slope in children with a heart, lung or muscle
      disease.
AB  - The purposes of this study were all to determine if DeltaVO2/DeltaWR is dependent
      on age, body mass, height and fitness and if DeltaVO2/DeltaWR could discriminate
      between healthy children and children with a chronic disease that limits O2
      delivery or utilization. Four groups were included: muscle disease (Juvenile
      Dermatomyositis; JDM; n=12), lung disease (Cystic Fibrosis; CF; n=13), Congenital
      Heart Disease (CHD; (n=13), and healthy children (n=44). All children performed a
      cardiopulmonary exercise test on a cycle ergometer with respiratory gas analysis.
      The DeltaVO2/DeltaWR was determined by linear regression using data from unloaded
      cycling to peak exercise. No associations were found between the DeltaVO2/DeltaWR
      and age, body mass and height in healthy children. DeltaVO2/DeltaWR was
      significantly correlated with VO2peak/kg (r=0.44; p<0.01). Children with JDM had
      lower DeltaVO2/DeltaWR values than healthy children (p=0.02), and
      DeltaVO2/DeltaWR tended to be lower in CHD and higher in CF (p=0.09 and p=0.08,
      respectively). DeltaVO2/DeltaWR may be more sensitive for conditions that are
      characterized by local hypo perfusion (as in JDM), than for conditions that are
      characterized by impaired oxygen delivery (i. e. CF or CHD).

PMID- 20157876
TI  - Reference intervals for aldosterone, renin, and the aldosterone-to-renin ratio in
      the population-based Study of Health in Pomerania (SHIP-1).
AB  - The renin-angiotensin-aldosterone system plays a key role in the regulation of
      human blood pressure. The aldosterone-to-renin ratio (ARR) is widely accepted for
      screening the primary hyperaldosteronism (PAL). Various cutoffs for positive PAL
      screening have been defined in patient cohorts from endocrinological referral
      centers and primary care. However, the distribution of the ARR in the general
      population is largely unknown. We aim to provide reference ranges for plasma
      aldosterone concentration (PAC), plasma renin concentration (PRC), and the ARR
      for the general population of north-east Germany. A cohort of 3 300 subjects
      participated in the first follow-up of the longitudinal, population-based Study
      of Health in Pomerania (SHIP). PAC and PRC were measured by radioimmunometric
      procedures. The reference interval was defined as the central 95% range between
      the 2.5(th) and 97.5(th) percentiles. A reference population comprising 1,347
      healthy subjects was selected. Sex and age-specific (25-54 and 55-74 years)
      reference ranges are presented. The upper reference limit for the ARR was 14.2
      and 20.3 in younger, and 22.4 and 25.5 in older men and women, respectively. Time
      of blood sampling had no influence on the ARR, while beta blockers, and agents
      acting on the renin-angiotensin system were associated with higher and lower ARR,
      respectively. Our upper reference limit for the ARR is clearly lower than
      previously reported values from studies of hypertensive patients in primary care
      or hypertension referral centers. We confirm that PAC and PRC are associated with
      various factors, including sex, age, intake of estrogen, and various
      antihypertensive medications.

PMID- 20157878
TI  - Chemical composition and evaluation of the anti-hypernociceptive effect of the
      essential oil extracted from the leaves of Ugni myricoides on inflammatory and
      neuropathic models of pain in mice.
AB  - The study analyzes the chemical composition of the essential oil obtained from
      the leaves of Ugni myricoides (Kunth) O. Berg (U. myricoides EO). The composition
      of the essential oil was characterized by GC-FID and GC-MS analysis, showing at
      least six major constituents: alpha-pinene (52.1%), 1,8-cineole (11.9%), alpha
      humulene (4.6%), caryophyllene oxide + globulol (4.5%), humulene epoxide II
      (4.2%) and beta-caryophyllene (2.9%). It demonstrates for the first time the
      systemic anti-hypernociceptive properties of this orally administered oil in
      inflammatory and neuropathic models of hypernociception in mice. The effects of
      U. myricoides EO and its major constituent, alpha-pinene, were compared with
      those of indomethacin or gabapentin, drugs used clinically to treat inflammatory
      and neuropathic processes. Like indomethacin (5 or 10 mg/kg, p.o.), U. myricoides
      EO (5-50 mg/kg, p.o.) was able to significantly prevent mechanical
      hypernociception induced by carrageenan or complete Freund's adjuvant (CFA) in
      mice. These effects were observed for up to 48 h after i.pl. injection of
      flogistic agents. Repeated treatment with U. myricoides EO (5-25 mg/kg, p.o.),
      alpha-pinene (5-50 mg/kg, p.o.), or gabapentin (70 mg/kg, p.o.) also abolished
      the mechanical sensitization induced by CFA, or following the partial ligation of
      the sciatic nerve (PLSN). The present results indicate that U. myricoides EO
      produces marked anti-hypernociceptive effects in carrageenan and CFA mechanical
      sensitization models, and also inhibited neuropathic pain-like behavior after
      PLSN with efficacy similar to that observed for indomethacin or gabapentin. The
      relevant effects shown by U. myricoides EO are related, at least in part, to the
      presence of alpha-pinene and may be of potential interest for the management of
      inflammatory and neuropathic pain.

PMID- 20157877
TI  - Inhibition of bone metastasis from breast carcinoma by rosmarinic acid.
AB  - Skeletal disorders are a common complication of breast cancer and will be found
      in the vast majority of women with metastatic disease. Our study showed that
      rosmarinic acid (RA) could inhibit the migration of MDA-MB-231BO human bone
      homing breast cancer cells dose-dependently. Furthermore, in ST-2 murine bone
      marrow stromal cells cultured with RA there was a significant and dose-dependent
      increase in alkaline phosphatase (ALP) activity, with the number and size of
      mineralized nodules increasing. According to Western blot and quantitative real
      time PCR assay, RA may inhibit bone metastasis from breast carcinoma mainly via
      the pathway of the receptor activator of NF kappaB ligand
      (RANKL)/RANK/osteoprotegerin (OPG) and by simultaneously suppressing the
      expression of interleukin-8 (IL-8). RA may thus be a good candidate for a new
      therapeutic approach in bone metastasis from breast carcinoma.

PMID- 20157879
TI  - Toosendanin inhibits hepatocellular carcinoma cells by inducing mitochondria
      dependent apoptosis.
AB  - Toosendanin, a triterpenoid derivative isolated from Melia toosendan Sieb. et
      Zucc., possesses different pharmacological effects in humans and an important
      value in agriculture. As indicated by previous reports, the molecular mechanisms
      of toosendanin's anticancer effects remain poorly clarified. In this study we
      used both in vivo and in vitro models to investigate the anti-cancer effects of
      toosendanin and their possible molecular mechanisms. In the in vitro experiment,
      human hepatocellular carcinoma cell lines [SMMC-7721(p53+) and Hep3B (p53-)] were
      coincubated with toosendanin of different concentrations (0.1~ 0.9 uM). Anti
      proliferation effects were observed to be in a dose- and time-dependent manner.
      The IC(50) of TSN treated after 72 h for SMMC-7721 and Hep3B cells was 0.5 uM and
      0.9 uM, respectively. Results from morphological analysis, annexin V staining,
      detection of caspases activity, and expressions of Bcl-2, Bax, and Fas indicated
      that the anticancer effects of toosendanin were associated with its induction of
      apoptosis via the mitochondria-dependent pathway in p53- and p53+ hepatocellular
      carcinoma cells. In the IN VIVO experiment, BALB/c mice were s.c. inoculated with
      mouse hepatocellular carcinoma H (22) cells. Both high-dose (0.69 mg/kg) and low
      dose (0.173 mg/kg) toosendanin administrated intraperitoneally resulted in
      strongly suppressive effects on the tumorigenicity and apoptotic response.
      Results from the immunohistochemistry for Bcl-2, Bax, as well as for Fas showed
      that the anticancer effects of toosendanin were induced via apoptosis in a
      mitochondria-dependent manner, which confirmed the findings in the in vitro
      experiment. The findings above demonstrate that toosendanin possesses strong
      anticancer effects in vivo and in vitro via inducing mitochondria-dependent
      apoptosis in hepatocellular carcinoma cells.

PMID- 20157880
TI  - Phenolic compounds as selective antineoplasic agents against multidrug-resistant
      human cancer cells.
AB  - Twelve phenolic compounds, including three stilbenes, two flavonoids, two
      coumarins, one neolignan, and four lignans, isolated from Euphorbia and
      Pycnanthus species or obtained by derivatization, were assayed for their
      potential antineoplastic efficacy in three human cancer cell lines: gastric
      (EPG85-257), pancreatic (EPP85-181), and colon (HT-29) carcinomas as well as
      derived multidrug-resistant sublines. In each case, two different multidrug
      resistant variants, i.e., cell lines with classical and atypical MDR phenotype,
      were used. The majority of the MDR cancer sublines showed increased sensitivities
      to the studied compounds when compared to the parental sublines. The most active
      compound was the flavonoid naringenin, found to be 15-fold more effective against
      the atypical MDR subline of gastric carcinoma than in parental drug-sensitive
      cells. Furthermore, the stilbene trans-3,5,3',4'-tetramethoxypiceatannol and the
      lignans 4'-hydroxy-3,3',4-trimethoxylignan and heliobuphthalmin also exhibited
      high antineoplasic activities against the classical MDR subline derived from
      gastric carcinoma. The results of this study suggest that some phenolic compounds
      might be valuable for the treatment of multidrug-resistant cancer cells.

PMID- 20157881
TI  - Successful bronchial artery embolization for refractory esophageal bleeding after
      failed endoscopic therapy.

PMID- 20157882
TI  - Direct endoscopic percutaneous jejunostomy placement with double balloon
      enteroscopy.

PMID- 20157883
TI  - Mesenteric panniculitis following colonoscopy, polypectomy, and epinephrine
      injection.

PMID- 20157884
TI  - Novel use of cryotherapy to control bleeding in advanced esophageal cancer.

PMID- 20157885
TI  - Primary malignant melanoma with surrounding melanosis in the anorectum.

PMID- 20157886
TI  - Esophagomediastinal and esophagobronchial fistulas associated with invasive
      aspergillosis.

PMID- 20157887
TI  - Endoscopic treatment of transcolonic misplacement of a percutaneous endoscopic
      gastrostomy tube.

PMID- 20157888
TI  - A case of jejunal choriocarcinoma detected by capsule endoscopy and double
      balloon endoscopy.

PMID- 20157889
TI  - New endoscopic over-the-scope clip system for closure of a chronic
      tracheoesophageal fistula.

PMID- 20157890
TI  - Endoscopic ultrasound in hepatobiliary hydatid disease.

PMID- 20157891
TI  - Rare gastric glomus tumor causing upper gastrointestinal bleeding, with review of
      the endoscopic ultrasound features.

PMID- 20157892
TI  - Pseudomelanosis of the stomach.

PMID- 20157893
TI  - An uncommon presentation of a common cancer.

PMID- 20157896
TI  - [Stapes piston in reconstruction of the stapedial superstructure].

PMID- 20157897
TI  - Nucleophilic phosphinidene complexes: access and applicability.
AB  - Syntheses, properties, and reactivities of nucleophilic phosphinidene complexes
      [L(n)M=P-R] are reviewed. Emphasis is placed on the electronic tuning of this
      emerging class of phosphorus reagents, using different ancillary ligands and
      coordinatively unsaturated transition-metal moieties. The difference in
      applicability of the established stable 18-electron and transient 16-electron
      phosphinidenes is addressed.

PMID- 20157898
TI  - Synthesis of carbohydrate-functionalized quantum dots in microreactors.

PMID- 20157899
TI  - Stereospecific isotopic labeling of methyl groups for NMR spectroscopic studies
      of high-molecular-weight proteins.

PMID- 20157900
TI  - Closthioamide: an unprecedented polythioamide antibiotic from the strictly
      anaerobic bacterium Clostridium cellulolyticum.

PMID- 20157901
TI  - Synthesis and structure of a carbene-stabilized pi-boryl anion.

PMID- 20157902
TI  - The impact of ion pair association upon the 1H NMR spectra of cationic complexes
      akin to Grubbs catalysts.
AB  - A reconsideration of the (1)H NMR spectra of cationic transition metal complexes
      exhibiting the features of cyclophanes on the basis of Mislow's classification of
      topic groups arrives at the conclusion that the spectral changes triggered by
      chiral counterions reflect an intracationic diastereotopication of enantiotopic
      protons rather than the existence of pairs of long-lived diastereomeric ion
      pairs.

PMID- 20157905
TI  - A pilot randomized controlled trial of sleep therapy in Parkinson's disease:
      effect on patients and caregivers.
AB  - OBJECTIVE: By means of a controlled trial, to investigate the efficacy,
      tolerability and feasibility of a multi-component sleep therapy intervention
      versus basic sleep hygiene education in PD patients with sleep disturbances and
      their live-in carers. METHODS: Patient-carer dyads were randomised to either of
      the two interventions. Quantitative measures of sleep, psychiatric and overall
      functioning were administered at baseline and two weeks after the intervention to
      patients and carers. RESULTS: Sleep disturbances in the PD patients improved
      significantly in both the groups. Between group comparisons in both carers and
      patients revealed no significant differences on any outcome measures. The
      intervention was found to be well tolerated, feasible and could easily be
      translated into the clinical setting. CONCLUSIONS: This pilot study makes the
      case for further, more rigorous study of pragmatic, non-pharmacological
      interventions for sleep disturbances in PD.

PMID- 20157904
TI  - Emotional support, negative interaction and DSM IV lifetime disorders among older
      African Americans: findings from the National Survey of American Life (NSAL).
AB  - OBJECTIVES: Both emotional support and negative interaction with family members
      have been linked to mental health. However, few studies have examined the
      associations between emotional support and negative interaction and psychiatric
      disorders in late life. This study investigated the relationship between
      emotional support and negative interaction on lifetime prevalence of mood and
      anxiety disorders among older African Americans. DESIGN: The analyses utilized
      the National Survey of American Life. METHODS: Logistic regression and negative
      binomial regression analyses were used to examine the effect of emotional support
      and negative interaction with family members on the prevalence of lifetime DSM-IV
      mood and anxiety disorders. PARTICIPANTS: Data from 786 African Americans aged 55
      years and older were used. MEASUREMENT: The DSM-IV World Mental Health Composite
      International Diagnostic Interview (WMH-CIDI) was used to assess mental
      disorders. Three dependent variables were investigated: the prevalence of
      lifetime mood disorders, the prevalence of lifetime anxiety. RESULTS:
      Multivariate analysis found that emotional support was not associated with any of
      the three dependent variables. Negative interaction was significantly and
      positively associated with the odds of having a lifetime mood disorder, a
      lifetime anxiety disorder and the number of lifetime mood and anxiety disorders.
      CONCLUSIONS: This is the first study to investigate the relationships among
      emotional support, negative interaction with family members and psychiatric
      disorders among older African Americans. Negative interaction was a risk factor
      for mood and anxiety disorders among older African Americans, whereas emotional
      support was not significant.

PMID- 20157906
TI  - Amminelithium amidoborane Li(NH3)NH2BH3: a new coordination compound with
      favorable dehydrogenation characteristics.
AB  - The monoammoniate of lithium amidoborane, Li(NH(3))NH(2)BH(3), was synthesized by
      treatment of LiNH(2)BH(3) with ammonia at room temperature. This compound exists
      in the amorphous state at room temperature, but at -20 degrees C crystallizes in
      the orthorhombic space group Pbca with lattice parameters of a = 9.711(4), b =
      8.7027(5), c = 7.1999(1) A, and V = 608.51 A(3). The thermal decomposition
      behavior of this compound under argon and under ammonia was investigated. Through
      a series of experiments we have demonstrated that Li(NH(3))NH(2)BH(3) is able to
      absorb/desorb ammonia reversibly at room temperature. In the temperature range of
      40-70 degrees C, this compound showed favorable dehydrogenation characteristics.
      Specifically, under ammonia this material was able to release 3.0 equiv hydrogen
      (11.18 wt %) rapidly at 60 degrees C, which represents a significant advantage
      over LiNH(2)BH(3). It has been found that the formation of the coordination bond
      between ammonia and Li(+) in LiNH(2)BH(3) plays a crucial role in promoting the
      combination of hydridic B-H bonds and protic N-H bonds, leading to
      dehydrogenation at low temperature.

PMID- 20157907
TI  - Stereoselective formation of triphenylene ketals.
AB  - The oxidative trimerization of catechol ketals by MoCl(5) or MoCl(5)/TiCl(4)
      mixtures leads preferentially to the all-syn stereoisomer of the corresponding
      triphenylene ketal. The concomitant metal salts of the oxidative coupling most
      probably form a multinuclear template that directs the diastereoselectivity in a
      subsequent isomerization step under electrophilic conditions. Several
      functionalities can serve as coordination sites for the multinuclear metal chloro
      clusters. Suitable functional groups have to be stable towards the strong
      electrophilic and oxidizing conditions. Therefore, esters, nitriles, nitro
      derivatives, triazoles, and pyridines are successfully employed. Based on the
      flexibility and size of the substrate, different reagent mixtures lead to the
      stereoselective formation of the all-syn derivatives.

PMID- 20157908
TI  - Squaraine-based [2]rotaxanes that function as visibly active molecular switches.

PMID- 20157909
TI  - Straightforward synthesis of substituted p-quinones: isolation of a key
      intermediate and use as a bridging ligand in a diruthenium complex.

PMID- 20157910
TI  - Directed evolution of an antitumor drug (arginine deiminase PpADI) for increased
      activity at physiological pH.
AB  - Arginine deiminase (ADI; EC 3.5.3.6) has been studied as a potential antitumor
      drug for the treatment of arginine-auxotrophic tumors, such as hepatocellular
      carcinomas (HCCs) and melanomas. Studies with human lymphatic leukemia cell lines
      confirmed that ADI is an antiangiogenic agent for treating leukemia. The main
      limitation of ADI from Pseudomonas plecoglossicida (PpADI) lies in its pH
      dependent activity profile, its pH optimum is at 6.5. A pH shift from 6.5 to 7.5
      results in an approximately 80 % drop in activity. (The pH of human plasma is
      7.35 to 7.45.) In order to shift the PpADI pH optimum, a directed-evolution
      protocol based on an adapted citrulline-screening protocol in microtiter-plate
      format was developed and validated. A proof of concept for ADI engineering
      resulted in a pH optimum of pH 7.0 and increased resistance under physiological
      and slightly alkaline conditions. At pH 7.4, variant M2 (K5T/D44E/H404R) is four
      times faster than the wild-type PpADI and retains approximately 50 % of its
      activity relative to its pH optimum, compared to approximately 10 % in the case
      of the wild-type PpADI.

PMID- 20157911
TI  - Sugar-selective enrichment of a D-glucose-substituted ruthenium bipyridyl complex
      inside HepG2 cancer cells.

PMID- 20157912
TI  - Chemical protein synthesis by kinetically controlled ligation of peptide O
      esters.

PMID- 20157913
TI  - Bio-interfaces--interaction of PLL/HA thick films with nanoparticles and
      microcapsules.
AB  - The interaction of biocompatible, exponentially grown films composed of poly-L
      lysine (PLL) and hyaluronic acid (HA) polymers with gold nanoparticles and
      microcapsules is studied. Both aggregated and non-aggregated nanoparticle states
      are achieved; desorption of PLL accounts for aggregation of nanoparticles. The
      presence of aggregates of gold nanoparticles on films enables remote activation
      by near-infrared irradiation due to local, nanometer confined heating. Thermally
      shrunk microcapsules, which are remarkably monodisperse upon preparation but gain
      polydispersity after months of storage, are also adsorbed onto films. PLL
      polymers desorbed from films interact with microcapsules introducing a charge
      imbalance which leads to an increase of the microcapsule size, thus films amplify
      this effect. Multifunctional, biocompatible, thick gel films with remote
      activation and release capabilities are targeted for cell cultures in biology and
      tissue engineering in medicine.

PMID- 20157914
TI  - Photovoltaic universal joints: ball-and-socket interfaces in molecular
      photovoltaic cells.

PMID- 20157915
TI  - Improved model of lanosterol 14alpha-demethylase by ligand-supported homology
      modeling: validation by virtual screening and azole optimization.
AB  - Lanosterol 14alpha-demethylase (CYP51) is an important target for antifungal
      drugs. An improved three-dimensional model of CYP51 from Candida albicans
      (CACYP51) was constructed by ligand-supported homology modeling and molecular
      dynamics simulations. The accuracy of the constructed model was evaluated by its
      performance in a small-scale virtual screen. The results show that known CYP51
      inhibitors were efficiently discriminated by the model, and it performed better
      than our previous CACYP51 model. The active site of CACYP51 was characterized by
      multiple copy simultaneous search (MCSS) calculations. On the basis of the MCSS
      results, a series of novel azoles were designed and synthesized, and they showed
      good in vitro antifungal activity with a broad spectrum. The MIC(80) value of
      four of these compounds against C. albicans is 0.001 microg mL(-1), indicating
      that they are promising leads for the discovery of novel antifungal agents.

PMID- 20157916
TI  - A structure-based virtual screening approach toward the discovery of histone
      deacetylase inhibitors: identification of promising zinc-chelating groups.
AB  - The inhibitors of histone deacetylases (HDACs) have drawn a great deal of
      attention due to their promising potential as small-molecule therapeutics for the
      treatment of cancer. By means of virtual screening with docking simulations under
      consideration of the effects of ligand solvation, we were able to identify six
      novel HDAC inhibitors with IC(50) values ranging from 1 to 100 muM. These newly
      identified inhibitors are structurally diverse and have various chelating groups
      for the active site zinc ion, including N-[1,3,4]thiadiazol-2-yl sulfonamide, N
      thiazol-2-yl sulfonamide, and hydroxamic acid moieties. The former two groups are
      included in many drugs in current clinical use and have not yet been reported as
      HDAC inhibitors. Therefore, they can be considered as new inhibitor scaffolds for
      the development of anticancer drugs by structure-activity relationship studies to
      improve the inhibitory activities against HDACs. Interactions with the HDAC1
      active site residues responsible for stabilizing these new inhibitors are
      addressed in detail.

PMID- 20157917
TI  - Enantioselective Friedel-Crafts alkylation of indoles, pyrroles, and furans with
      trifluoropyruvate catalyzed by chiral phosphoric acid.

PMID- 20157927
TI  - Nanostructured carbon and carbon nanocomposites for electrochemical energy
      storage applications.
AB  - Electrochemical energy storage is one of the important technologies for a
      sustainable future of our society, in times of energy crisis. Lithium-ion
      batteries and supercapacitors with their high energy or power densities,
      portability, and promising cycling life are the cores of future technologies.
      This Review describes some materials science aspects on nanocarbon-based
      materials for these applications. Nanostructuring (decreasing dimensions) and
      nanoarchitecturing (combining or assembling several nanometer-scale building
      blocks) are landmarks in the development of high-performance electrodes for with
      long cycle lifes and high safety. Numerous works reviewed herein have shown
      higher performances for such electrodes, but mostly give diverse values that show
      no converging tendency towards future development. The lack of knowledge about
      interface processes and defect dynamics of electrodes, as well as the missing
      cooperation between material scientists, electrochemists, and battery engineers,
      are reasons for the currently widespread trial-and-error strategy of experiments.
      A concerted action between all of these disciplines is a prerequisite for the
      future development of electrochemical energy storage devices.

PMID- 20157929
TI  - Evaluation of lufenuron as a chemosterilant against fruit flies of the genus
      Anastrepha (Diptera: Tephritidae).
AB  - BACKGROUND: Chemosterilisation with lufenuron bait stations is a recently
      developed technique that is being implemented for Ceratitis capitata Wiedemann
      control. The aim of this work was to evaluate the chemosterilising effect of
      lufenuron against four economically important Latin American fruit flies species:
      Anastrepha ludens (Loew.), A. obliqua Macquart, A. serpentina Wiedemann and A.
      striata Schiner (Diptera: Tephritidae) in order to design a similar strategy for
      their control. RESULTS: Sexually mature adults were treated by ingestion with
      concentrations ranging from 0.1 to 30.0 mg g(-1) of lufenuron in the diet. In
      addition, conspecific crosses with only one of the sexes being treated (30.0 mg
      g(-1)) were performed in order to appraise the contribution of each sex to the
      sterilising effect. In all cases, fecundity was not affected by the treatments,
      as opposed to fertility where all Anastrepha species studied were significantly
      affected, although to different extents. The conspecific crosses showed that
      treated males of A. ludens, A. obliqua and A. serpentina were not able to
      transmit the sterility to their respective untreated females. Only in the case of
      A. striata did crossing treated males with untreated females significantly
      reduced egg hatch. CONCLUSION: Although further investigations are required, the
      present results demonstrate that the use of lufenuron for controlling A. striata
      could be potentially viable.

PMID- 20157930
TI  - When, and on what basis, do physicians decide to ignore a patient's choice in
      favor of administering a treatment involuntarily?

PMID- 20157931
TI  - [A need for rapid establishment of a licensure system for psychiatric
      technologists].

PMID- 20157932
TI  - [A request from academic conferences--establishment of a national licensure
      system for "functional psychologists (clinical psychologists) who practice in the
      medical field].

PMID- 20157934
TI  - [Personnel management at the Neuropsychiatry Department, Kochi University].

PMID- 20157933
TI  - [To bring about the team care that is being desired].

PMID- 20157936
TI  - [The position of psychiatric departments in the management of university
      hospitals].

PMID- 20157935
TI  - Effect of microwave postpolymerization treatment and of storage time in water on
      the cytotoxicity of denture base and reline acrylic resins.
AB  - OBJECTIVES: To evaluate the effect of microwave postpolymerization heat treatment
      and water storage time on the cytotoxicity of denture base and reline acrylic
      resins. METHOD AND MATERIALS: Sample disks of 6 acrylic resins were fabricated
      under aseptic conditions (Kooliner, GC; Tokuyama Rebase II, Tokuyama Dental; New
      Truliner, Bosworth; Acron MC, GC; Lucitone 550, Dentsply; QC 20, Dentsply). The
      denture base acrylic resin samples were stored in water for 24 and 48 hours at 37
      degrees C. The fabricated samples were further subdivided into 2 groups: (1)
      samples without heat treatment and (2) samples treated in a microwave. The 3H
      thymidine incorporation test was used to determine the cytotoxicity of the
      materials. The data were statistically analyzed using the incomplete 3-way ANOVA
      and Tukey HSD tests (P < .05). RESULTS: Microwave postpolymerization heat
      treatment improved the biocompatibility of Tokuyama Rebase II. Tokuyama Rebase II
      without heat treatment and Acron MC in both experimental groups were graded as
      slightly cytotoxic in the group without water storage. The other resins were
      graded as noncytotoxic. After 24 hours of immersion in water, all materials were
      graded as noncytotoxic. After water storage for 48 hours, Acron MC without heat
      treatment and QC 20 in both experimental groups were graded as slightly
      cytotoxic. Lucitone 550 was graded as noncytotoxic in all experimental groups.
      CONCLUSION: Microwave irradiation may be considered an alternative to reduce the
      cytotoxicity of Tokuyama Rebase II. Dental practitioners should choose Lucitone
      550 processed with terminal boiling stage.

PMID- 20157937
TI  - [The role of university hospital psychiatric department in community health
      care].

PMID- 20157938
TI  - [Contribution of university hospitals to regional medical care--from the practice
      of tertiary emergency service by the psychiatric department].

PMID- 20157939
TI  - [Ideal status of research and training of researchers at university psychiatry
      departments].

PMID- 20157940
TI  - [Training in clinical research at university psychiatry departments].

PMID- 20157941
TI  - An early warning sign: sexually transmissible infections among young African
      American women and the need for preemptive, combination HIV prevention.

PMID- 20157943
TI  - Abstracts of the 18th Annual Research Conference and Workshop on Child Health:
      From the Womb to Adolescence. November 11-13, 2009. Kingston, Jamaica.

PMID- 20157944
TI  - Unique developmental differences associated with ASD.

PMID- 20157942
TI  - Social marketing strategy to increase awareness of non-occupational post-exposure
      prophylaxis (NPEP) followed by increased NPEP awareness and more appropriate use.

PMID- 20157945
TI  - GUT 2009. Abstracts of the Annual Scientific Meeting of the Malaysian Society of
      Gastroenterology and Hepatology, 14-16 August 2009. Langkawi Kedah, Malaysia.

PMID- 20157946
TI  - Abstracts of the 45th Annual Meeting of the Argentine Society for Biochemistry
      and Molecular Biology Research, 10-13 November 2009. San Miguel de Tucuman,
      Argentina.

PMID- 20157948
TI  - Find resources to help patients pay for cancer care.

PMID- 20157947
TI  - Application of quality-of-life  measurements in clinical trials  and in clinical
      practice for  gynecologic cancer patients.
AB  - Gynecologic cancer teams care for women with malignancies of the ovaries,
      fallopian tubes, uterus, cervix, vagina and vulva. Gynecologic cancer therapies
      have become increasingly tailored to individual risk factors and are frequently
      multimodal. Clinical trials are necessary to assess the effectiveness of new
      treatment regimes, and measurement of differences in impact on quality of life
      (QoL) has become as important as assessment of disease-free and overall survival.
      Site-specific gynecologic cancer QoL measurement tools have been developed to
      improve the sensitivity of QoL assessment and to capture a broad range of issues
      relevant to each specific cancer and treatment modality. QoL assessment tools
      must be valid, reliable and sensitive to measure the differences in QoL domains
      in the populations in which they are used, and their development must be
      methodologically sound and transparent in order that researchers can have
      confidence that the instruments are fit for purpose. With improving survival
      rates for most gynecologic malignancies, survivorship issues are becoming
      increasingly important, relating to all domains of QoL. Patient-reported outcome
      measures are becoming integral components of cancer follow-up pathways and
      survivorship programs, identifying physical, psychological or functional legacies
      that impact on QoL during the months and years following the completion of cancer
      treatment. Late effects that impact on sexual functioning are becoming especially
      important for cancers with effective treatment regimes affecting younger women.
      The development of valid outcome measures for assessment of sexual function for
      gynecologic cancer patients is a priority.

PMID- 20157949
TI  - Oncology nurses can help patients save costs by managing their medications.

PMID- 20157950
TI  - Practice safe nursing with oral hazardous drugs.

PMID- 20157951
TI  - When patients can't afford to have cancer.

PMID- 20157952
TI  - Transdermal medication delivery helps prevent CINV.

PMID- 20157953
TI  - Daily doses of imatinib may improve survival for children with high-risk
      leukemia.

PMID- 20157954
TI  - Prolonged hospitalization in patients with cancer: how long is too long?

PMID- 20157955
TI  - Whanau Ora: rethinking the way in which health services are delivered to Maori.

PMID- 20157956
TI  - Swimming against the malestream: men choosing nursing as a career.
AB  - This article reports on one aspect of a larger study, which used qualitative
      methods to critically explore the social construction of men as nurses. It draws
      upon literature pertaining to gender and nursing, and interviews with 18 New
      Zealand men to describe the factors underpinning decisions to turn away from
      malestream occupations and enter a profession stereotyped as 'women's work'. Five
      thematic groupings are revealed to be significant with respect to the decision
      making process: formative experiences, the Call, expediency, personal
      acquaintance with a nurse and personal fulfilment. These factors, however, do not
      necessarily operate in isolation. The reasons for becoming nurses are complex and
      multifactorial. In comparison to the experiences reported in the international
      literature, the men in this study were more focused on human caring and the
      transformational potential for personal fulfilment rather than a focus on the
      barriers to their engagement with nursing.

PMID- 20157957
TI  - Graduate nurses' experience of postgraduate education within a nursing entry to
      practice programme.
AB  - The first year of practice is usually a challenging time for nursing graduates.
      In New Zealand most undertake a Nursing Entry to Practice (NETP) programme aimed
      at socialising them into their new role and work environment. Some of these
      programmes now have embedded postgraduate courses. This means that graduates
      undertake higher education while at the same time adjusting to a new role and
      work environment. Using a cross-sectional survey design the purpose of this study
      was to explore graduate nurses' experiences of postgraduate education within a
      NETP programme. Overall, participants felt well prepared for postgraduate studies
      at academic, personal and professional levels, although most suggested that NETP
      programmes could allow for a stand-down period of three to four months before
      postgraduate education is introduced. This would give the graduate an opportunity
      to adjust to the clinical environment. They also highlighted the importance of
      making expectations clear from the outset. This study revealed that the number
      and nature of postgraduate courses offered in a NETP programme requires further
      investigation.

PMID- 20157958
TI  - Senior nurses' perceptions of cultural safety in an acute clinical practice area.
AB  - Cultural safety is a concept that emerged within the New Zealand nursing context.
      The purpose is to ensure that nursing practice is congruent with the aims and
      objectives of the Treaty of Waitangi (the founding document between Maori and the
      Crown) and so facilitates the nursing of patients regardful of all that makes
      them unique and individual. While cultural safety has continued to develop since
      its inception in the 1980s, there remains relatively little research looking at
      its application in practice. This is due in part to the core element that
      recognises that only the recipient of care can determine if cultural safety has
      occurred. There are inherent difficulties in questioning patients about the
      quality of their care from a cultural safety perspective. One of these is the
      uncertainty around the public perception and understanding of cultural safety
      together with the implications of asking a vulnerable group to comment on this
      aspect of care. An alternative to asking patients to comment on whether they
      received culturally safe care is to consider the perceptions of health care
      professionals regarding this concept. This paper presents the results of a small
      study aimed at eliciting the beliefs and attitudes of a group of senior nurses
      with respect to the concept of cultural safety, and their perception of its role
      in clinical practice. It was undertaken as a preliminary to a wider survey.

PMID- 20157959
TI  - Workplace violence experienced by registered nurses: a concept analysis.
AB  - Workplace violence toward nurses has increased during the last decade with
      serious consequences that may extend beyond individual nurses to an entire health
      care organisation. The variety of definitions of workplace violence experienced
      by registered nurses contribute to a lack of clarity about what it constitutes,
      which in turn jeopardizes the reporting of incidences by nurses. Drawing on the
      relevant literature from 1990 to 2005, a concept analysis using Walker and
      Avant's framework was undertaken to develop an operational definition of this
      phenomenon as experienced by registered nurses (excluding mental health nurses).
      Having a clear understanding of workplace violence assists with the creation of
      strategies aimed at preventing and/or resolving this problem.

PMID- 20157960
TI  - Medicine beyond borders: the legal and ethical challenges.
AB  - The ease and affordability of international travel has contributed to the rapid
      growth of the healthcare industry where people from all around the world are
      traveling to other countries to obtain medical, dental, and surgical care while
      at the same time touring, vacationing and fully experiencing the attractions of
      the countries that they are visiting. A combination of many factors has led to
      the recent increase in popularity of medical tourism such as exorbitant costs of
      healthcare in industrialized nations, favorable currency exchange rates in the
      global economy, rapidly improving technology in many countries of the world and
      most importantly proven safety of healthcare in selected foreign nations.
      Nevertheless, the development of medical tourism has certainly awakened many
      ethical and legal issues, which must be addressed. Issues pertaining to
      malpractice, consumer protection, organ trafficking, alternative medicine and
      telemedicine need comprehensive legal regulatory framework to govern them.
      Ethical issues are also been raised by the promotion of medical tourism in
      particular those pertaining to doctor and patient relationship. A future, where
      medical law is subsumed into various legal and ethical dimensions, poses serious
      challenges for the practice and ethics of medicine.

PMID- 20157961
TI  - The phenomenon of physical aggression against health service personnel: different
      perspectives.
AB  - The doctor-patient relationship has undergone important changes in recent years.
      Increasing levels of distrust, on the part of patients towards professionals and
      institutions, have led to an increase of conflicts resulting in violent actions
      against health service personnel. The aim of this study is to analyse this
      phenomenon in the public welfare services of the Region of Murcia (Spain), based
      on an analysis of accusations, as were presented by doctors in courts in the
      period between 2006 and April 2008. The conclusion reached can presumably be
      extrapolated to the rest of Spain. The violent reactions in question resulted
      from patients demanding drug prescriptions; the prolongation of sick leave and
      the demand for diagnostic tests. The Public Health Services provide directives to
      anticipate and avoid such situations, emphasize the training of professionals in
      communication skills, the promotion of skills of negotiation and emotional self
      control. Other measures include the installation of alarms, intercoms and video
      cameras, contracting security companies, collaboration with the police and
      posters in health facilities warning that legal action will be taken.
      Nevertheless, given the obvious inadequacy of the above-mentioned measures, Plans
      of Prevention have been put in place. In addition legal defence has been granted
      to all such professionals. From the judicial point of view, these aggressions are
      judged as minor crimes of injury, insult and threat. The most recent view taken
      on such conduct is to consider it as a crime of attempt or offence against the
      authority, which has been confirmed in law by the recent judgment passed down by
      the Spanish High Court on 4th December, 2007.

PMID- 20157962
TI  - Enforced dismissal of Dutch patients who are not motivated to leave forensic
      psychiatric settings and treatment--is it ethically acceptable?
AB  - The ethical issues surrounding enforced release of forensic psychiatric patients
      are discussed in this article. Some patients disagree with their discharge
      because they are convinced that they need the continued structure of the hospital
      setting and the social relationships with fellow patients and therapists. They
      fear that without this structure they will unable to cope with the challenges of
      life in society and the consequence could be relapse and recidivism. Suggestions
      for guidelines on a practical approach to this category of forensic patients are
      presented.

PMID- 20157963
TI  - Personal autonomy, good care, informed consent and human dignity--some
      reflections from a European perspective.
AB  - Respecting and protecting personal autonomy requires that autonomy is interpreted
      in conjunction with the principle of good care in a way consistent with (the
      aspirations enshrined in) human dignity. This leads to a principled and
      relational approach towards personal autonomy. This implies an active role of
      health care providers, as councillors of patients, and a personalised way of
      obtaining informed consent, to maximally ensure the enjoying personal autonomy.

PMID- 20157964
TI  - End- of- life decisions and minors: do minors have the right to refuse life
      preserving medical treatment? A comparative study.
AB  - The principles of the right to informed consent and informed refusal are quite
      clear for competent adult patients. The right of a competent adult patient to
      give his informed consent before medical treatment can be started, is a patients'
      right that is recognised all over the world. The logical corollary of the right
      to informed consent is the right to informed refusal. A competent adult patient
      also has the right to refuse medical treatment by simply withholding or
      withdrawing his consent. A physician who starts medical treatment without the
      informed consent of his patient will be held liable for battery. Can these same
      principles be applied to minors? In other words: do minors also have the right to
      refuse medical treatment? Can a minor refuse even life preserving care? The
      interests of the involved parties (minor, parents and state) have to be weighed
      against each other case by case. A thorough examination of the available case law
      shows that the best interests of the minor are paramount. This "best interests"
      standard guides judges in their making of a decision. However, this is certainly
      not always in accordance with reality. In fact, minors can be mature enough to
      refuse treatment at a much earlier time than the age of legal majority, whatever
      the consequences of that refusal may be.

PMID- 20157965
TI  - Children employed in the performing arts, advertising and fashion industry: what
      legal protection do they have?
AB  - Ill-treatment can sometimes take on an unfamiliar face. Particularly, this is the
      case for certain types of child employment. In France, as in most European
      countries, there are laws for protecting children and guaranteeing their right to
      schooling. Over and above the frequently observed apprenticeship contracts,
      obtained by eligible under 16 years, there is also the dispensatory case of
      children employed in the performing arts, advertising and the fashion industry.
      In France, legislators take the child's vulnerability into account when
      developing legislative and regulatory mechanisms, concerning the modalities of
      his/her professional activity, particularly in artistic fields and in fashion
      modelling. Since both may employ very young children, or even infants, one
      essential question ought to be raised: from a legal point of view, are these
      children sufficiently protected, with regard to the potential physical and
      psychological consequences of their particular professional activities?

PMID- 20157966
TI  - United States laws and the rights of the terminally ill.
AB  - United States laws that pertain to the rights of terminally ill patients include
      both Federal law and the laws of the individual States. These laws affect the
      structure and use of Advance Directives that patients prepare to provide guidance
      and direction as to how they wish to be treated in the event of their mental and
      physical incapacity. The manner by which individuals are treated when they lose
      decisional capacity may be subject to decisions of federal courts and ultimately
      the United States Supreme Court. These decisions address the balance between an
      individual's autonomy to direct how he or she wishes to be cared for when no
      longer capable of making personal decisions, the role and rights of designated
      decision makers for such individuals, and the role and authority of States to
      direct how such care can or should be provided. A separate set of decisions
      pertain to the issue of physician-assisted suicide. These again seek to balance
      the rights of individuals versus the authority and responsibility of government.
      As with decisions affecting care of the terminally ill, decisions arise from
      State law but may end up in judicial decisions of the United States Supreme
      Court. The decisions by the United States Supreme Court have resulted in
      differences among the States as to how physician-assisted suicide is managed.
      Finally, recent decisions have affected the access of terminally ill patients to
      drugs that have not been approved by the United States Food and Drug
      Administration (FDA) for general use. They address the rights of terminally ill
      patients to unapproved drugs versus the authority and responsibility of the FDA
      to regulate the availability of drugs.

PMID- 20157967
TI  - Ethical bodies: are they possible under democratic systems? The Turkish example.
AB  - In this article, the relationship between ethics bodies and democratic concepts
      will be introduced. One should bear in mind that the relationship between the
      flourishing of ethics committees (EC) and democracy is by no means undirectional.
      The line of causation can easily be reversed as a higher level of democracy is
      likely to lead to a spurt in such committees at different levels of society. It
      is not a coincidence that they appear in larger numbers in relatively more open
      and democratic societies. In this sense, their sheer existence might be taken as
      a sign of a higher level of awareness for openness and democracy. EC seems to
      have some functions theoretically: To contribute to the eradication of corruption
      in society; To increase the accountability of different sections of the
      population; To play an important part in increasing the awareness about the
      rights and duties; To contribute to the spread of self-disciplining behavior in
      society; One final point to be emphasized is that for ethical committees to
      fulfill the above functions they should have a clear set of guidelines, powers to
      enforce them and effective deterrents to prevent wayward behavior. The principal
      question of how it does works in Turkey--a country located at the junction of
      Europe and Asia--ought to be perceived from the point of view of a medical
      ethicist from a developing country.

PMID- 20157968
TI  - Doctors and pharmaceutical industry.
AB  - The pharmaceutical industry is seen as seducing doctors by providing expensive
      gifts, subsidising travel and underwriting practice expenses in return for those
      doctors prescribing products that otherwise they would not use. This paints
      doctors in a very negative light; suggests doctors are available to the highest
      bidder; implies doctors do not adequately act as independent agents; and that
      doctors are driven more by self-interest than by patient needs. Similar
      practices, in other industries, are accepted as normal business behaviour but it
      is automatically assumed to be improper if the pharmaceutical industry supports
      doctors. Should the pharmaceutical industry withdraw educational grants then
      there would be: fewer scientific meetings; reduced attendance at conferences;
      limited post graduate education; and a depreciated level of maintenance of
      professional standards. To suggest that doctors prescribe inappropriately in
      return for largesse maligns their integrity but where there is no scientific
      reason to choose between different treatments then there can be little argument
      against selecting the product manufactured by a company that has invested in the
      doctor and the question arises as to whether this represents bad medicine? This
      paper will examine what constitutes non-professional conduct in response to
      inducements by the pharmaceutical industry. It will review: conflict of interest;
      relationships between doctors and pharma and the consequences for patients; and
      the need for critical appraisal before automatically decrying this relationship
      while accepting that there remain those who do not practice ethical medicine.

PMID- 20157969
TI  - Conflict of interests--criticising the critics.
AB  - Examining the relationship between the pharmaceutical industry and medical
      profession the BMJ raised concern including: describing doctors as 'lapdogs to
      drug firms'; unethical recruiting in third world countries; manipulating codes of
      conduct; and medicine corrupted by industry largess. This paper offers an
      alternative perspective, questioning if largess is automatically contrary to
      societal needs. Serving on advisory boards allows critical input. Critics who
      denigrate those who accept support often have undisclosed conflicts of interest.
      These critics usually do not come from private practice and hence responsible for
      their own expenses and do not acknowledge costs faced by private practitioners
      when attending meetings. Private practice does not provide salary when not
      consulting, has no trust fund support and cannot amortise sponsorship as is often
      done in the public sector. Failure to disclose this represents concealed conflict
      of interest, amplified by the 'publish or perish' philosophy, which may well
      underwrite some publications.

PMID- 20157970
TI  - Donation of eggs in assisted reproduction and informed consent.
AB  - In Spain, there exists an increasing amount of advertising for the donation of
      eggs for assisted reproduction. This study attempts to assess: (1) scientific
      evidence available about adverse effects of egg donation; (2) characteristics of
      the information given in the informed consent to donors; and (3) the legality of
      this advertising. The main results are: (1) Many severe problems are associated
      with induction of ovulation, as ovarian hyperstimulation (reported frequencies
      from 5.9 to 15%), thromboembolism, hepatic failure and increased risk of ovarian,
      breast, endometrial and colon cancer. (2) Informed consent for egg donors is very
      incomplete, according to the Spanish law 41/2002 on Patient's Information. (3)
      Current advertising to promote egg donation does not respect, among others, law
      14/2006 about Assisted Human Reproduction, as it includes reference to economic
      compensation or benefits but no information about the risks. Deontological and
      judicial disciplinary procedures should be initiated to protect donors' rights.

PMID- 20157971
TI  - Legal aspects of the withholding and withdrawing of intensive care in extremely
      premature infants.
AB  - Extremely premature infants--i.e. infants born at less than 27 weeks gestation-
      often face a grim prognosis. Hence, the question arises whether they should
      always be given intensive care and who should be the one deciding about that.
      This article explores these issues and starts from empirical data on the outcome
      of extremely premature infants to develop a legal framework. Throughout
      international literature, it seems there is a consensus that intensive care
      should not be given at a gestational age of less than 23 weeks, but should
      principally always be started from 25 weeks gestation on. Within the so-called
      grey zone (i.e. at 23 - 24 weeks gestation) however, different approaches are
      defended. Only the start- and revaluate approach is ethically and legally
      justified. When it comes to deciding about the treatment course of the infant,
      parents should be the final decision-maker as they have to live with the
      consequences of the decision.

PMID- 20157972
TI  - Cultural influences on medical law.
AB  - The law concerning assisted conception is particularly challenged when there is a
      breakdown in the relationship between a couple who has embarked on treatment and
      the treatment has already reached the stage of producing embryos ready for
      transplantation. The right of either party to use or to destroy the embryos may
      be the subject of a legal battle between them. Two cases of this nature, which
      resulted in differing decisions, are the English case of Evans v Amicus
      Healthcare Ltd and the Israeli case of Nachmani v Nachmani. The legal reasoning
      behind the decisions is explored within a subtext of differing attitudes to
      assisted conception in England and Israel.

PMID- 20157973
TI  - Clinical guidelines as a tool for legal liability. An international perspective.
AB  - Clinical guidelines are statements that have been systematically developed and
      which aim to assist clinicians in making decisions about treatment for specific
      conditions. They are linked to evidence and are meant to facilitate good medical
      practice. A key issue that follows is how lawyers and the courts might use such
      guidelinesin medical litigation. The multiplicity of opinions and scientific
      professions requiring expertise might influence the expert submitting an opinion
      to base his opinion on scientific theses which have not been recognized
      scientifically, are not based on facts and are not supported by professional
      literature. Medical evidence has to be methodically based and reliable. In recent
      years the medical community has developed a new field called "Evidence Based
      Medicine", meaning, use of medical information based on the best information in
      the medical literature relevant to the condition being treated. Evidence Based
      Medicine distinguishes between recognized scientific theories and what is called
      "Junk Science". Clinical Guidelines are of value in systematizing medical
      procedures, mainly those which may have legal implications. In other procedures
      Guidelines may serve the Court as a source of sound information, provided they
      are the product of a recognized professional body, and proven to bear no relation
      to a body which may have interests in the delivery of healthcare. Clinical
      guidelines are set as normative standards and used as a tool to indicate the
      standard of care at the time. They can be used as a tool for assessment of the
      questionable conduct. Guidelines are consulted by courts because they provide
      evidence of standards justified in relation to evidence rather than custom, this
      helps the courts test the expert evidence that radically strengthen the normative
      dynamic of the law in actions alleging medical negligence. As clinical practice
      guidelines become more and more prevalent, some authors believe they will define
      the requisite "standard of care" for medical treatment and impact medical
      malpractice litigation. They may even replace expert testimony.

PMID- 20157974
TI  - Comparative analysis of medicolegal compensation for occupational cancers in
      France and other western European countries: development proposals.
AB  - In France, contemporary medicolegal reparation system of occupational diseases-
      in particular occupational cancer--has been questioned, constantly, due to
      changes in the state's legal system. For a long time, associated legislation was
      considered as a genuine social breakthrough. However, it shall remain
      acknowledged that over the past 15 years, it has been the French legal system
      itself that generated a certain level of inequality among victims of occupational
      diseases.. This inequality came to exist following certain jurisdictional
      understandings of legal matters, as well as the creation of exceptional schemes
      for granting compensation for physical injuries. It is agreed by both, courts and
      compensatory funds, that full compensation must be granted for particular group
      of victims. Yet, this is not the case as for granting compensation over
      occupational diseases, where reparation is on a set lump sum basis. In light of
      this proved inequality in the France legal system, with regard to the medicolegal
      reparation for loss or damage, associated with a claimant's occupational
      activity, we aim at investigating the procedures as practiced in various European
      countries occupational cancer in order to identify optimal compensation for these
      disorders.

PMID- 20157975
TI  - Methodological and ethical quality in phase III--breast cancer trials.
AB  - OBJECTIVE: The gold standard of Evidence Based Medicine remains the randomised
      controlled trial (RCT), which is the only tool that allows an approach to the
      "therapeutic truth". To reach credible conclusions, these trials need to be
      perfect in methodological and ethical quality. The purpose of this study is to
      evaluate methodological quality (MQ), ethical quality (EQ) and compliance with
      ethical requirements in phase III randomized clinical trials of breast cancer
      treatment. STUDY DESIGN: MQ was evaluated by the Jadad-scale and EQ by the Berdeu
      score for all the randomised controlled clinical trials (RCT) (n = 137),
      published between January 2001 and December 2005 in 11 international journals.
      RESULTS: Mean MQ was 9.88 +/- 1.43. MQ was insufficient (Jadad score pound 9) for
      49 RCT (35,8%). Mean EQ was 0.45 +/- 0.12. Mean EQ for RCT with insufficient MQ
      (n = 49) was 0.43 +/- 0.12; Mean EQ for RCT with good MQ (Jadad score > 9)(n =
      88) was 0.46 +/- 0.11. There was significant improvement in MQ depending on the
      year in which the study was started (p = 0.002). EQ was independent of the year
      of study's start (p = 0.134).There was no relationship between MQ or EQ and the
      number of patients included in the study (p = 0.53 and p = 0.1). There was a
      tendency towards correlation between MQ and EQ (p = 0.052), but the correlation
      between these two variables could not be considered as significant (r = 0.67).
      Informed consent from patients (ICP) was not obtained in 5.8% (n = 8) of the RCTs
      and the approval of a research ethics committee (REC) was not mentioned in 26.3%
      (n = 36) of the RCTs. CONCLUSIONS: Good MQ and reporting of ethical requirements
      (EQ) reflects the respect shown to the patients during the whole research
      process. There are still deficiencies in EQ and MQ. Quality improvement requires
      education and appropriation by the scientific community, in particular, medical
      staff, of methodological and ethical basic rules concerning trials involving
      human beings.

PMID- 20157976
TI  - The importance of the training of Ethics Committee members.
AB  - Research Ethics Committees (RECs) carry out the important task of humanizing
      clinical trials. While current Italian and international legislation dedicates
      considerable attention to REC composition, with consensus on several vital
      guidelines, no such univocal guidelines are available for REC training in Europe.
      In Italy, the activity of RECs is subject to moral, civil and criminal
      responsibility, but the issue of their preparation has been addressed only
      marginally. This article deals with the Italian situation, thus aims at exploring
      the question of REC training and trying to identify solutions. Committee members
      need both initial and continuing education and training in research ethics,
      methodology and governance.

PMID- 20157977
TI  - Patient mobility in the European Union: pushing for EU internal health market.
AB  - Having access to high-quality healthcare is a priority issue for European
      citizens and is recognised by the Charter of Fundamental Rights of the EU. The
      right to healthcare also encompasses situations where patients travel from one EU
      Member State to another and receive treatment there. This paper will explore the
      contradictory relation between the competence of EU Member States to regulate
      their health systems on their own, on the one hand, and free movement of services
      in the European Union, on the other hand. It will discuss the consequences of the
      decisions of the European Court of Justice in this field and the provisions of
      the Proposal for a Directive on Patients' Rights in Cross-Border Healthcare,
      especially in the light of opening up of EU Member States' healthcare markets,
      the need to control national healthcare expenditures and to protect the welfare
      state and the population of the host state.

PMID- 20157978
TI  - Patient mobility migration and mitigation--the devil and the deep blue sea.
AB  - In light of South Africa's economically powerful status in sub-Saharan Africa and
      its current constitutional directives, there exists arguably a duty on the State
      to ensure, proactively as opposed to reactively, that quarantine laws are
      consistent with the Constitution. Such a proactive approach to the mere
      possibility of dealing effectively with a public health emergency is, in my view,
      entirely consistent with every South African's right to expect and receive
      reasonable healthcare and possibly also an environment that is not detrimental to
      their health or well being, their security, their dignity and their lives.

PMID- 20157979
TI  - The field of forensic psychology in Israel--the state of the discipline.
AB  - The process of the establishment of forensic psychology in Israel begins in the
      eighties; while at the past 6 years after the creation of the Department of
      Psychology, Law and Ethics--The International Center for Health, Law and Ethics
      at Haifa University, the field continues to grow rapidly. Today, the development
      of forensic psychology is reflected in the scientific practice at Haifa
      University as at others (academic courses for different graduate levels and
      research concerning professional and ethical issues); as well as in the practical
      professional development of professional organizations, practice standards and
      training programs. Now as a specialty, forensic psychology must continue to make
      an effort to enrich in science and in professional practice, its aid in the
      administration of justice by assisting legal decision-makers.

PMID- 20157980
TI  - Pharmacists' responsibility and potential liability regarding generic
      substitition.
AB  - The generic medicines market in Australia is continuously growing and there is a
      push by the government towards generic substitution. However, generic dispensing
      places additional time constraints on pharmacists. There is also an increased
      need for professional judgement, and hence increased risk of error. Generic
      dispensing consequently places an increased responsibility on pharmacists, with a
      subsequent increased practice and liability risk. It is therefore important that
      pharmacists implement good practice standards and guidelines in order to manage
      their liability with regard to generic dispensing in both community and hospital
      pharmacy practice.

PMID- 20157981
TI  - Patient violence towards nursing staff in closed psychiatric wards: it's long
      term effects on staff's mental state and behaviour.
AB  - The purpose of this study was to (a) investigate in the Israeli context how
      patient violence towards staff (nurses and auxiliaries) affects their mental
      state and professional performance; and (b) to investigate how the variable,
      internal/external locus of control, mediates the effects of this violence. Four
      of the five hypotheses were confirmed: type, severity and frequency of attack was
      correlated with the level of staffers' psychological distress and change in
      professional functioning; psychological distress was correlated with a negative
      change in professional functioning and was higher in attacked staff than in those
      not attacked; internal locus of control was correlated with lower psychological
      distress and less negative professional functioning, whereas an external locus of
      control correlated with higher distress and more negative functioning. A sharper
      awareness of the effects of violence on staff is vital at all levels of
      management. Most attention is given to physical injury but verbal aggression and
      threats, often disregarded, may have the strongest negative influence.
      Emotional/psychological injury was rarely treated and needs to be.

PMID- 20157982
TI  - Legal aspects of end-of-life decision policies in health care institutions.
AB  - Nowadays, health care institutions develop policies on how to deal with medical
      decisions concerning the patients' end-of-life stage (hereafter: "end-of-life
      decision policies" or "ELD-policies"). This evolution is not only noticeable in
      hospitals, but also in nursing homes, residential facilities for the disabled and
      home care services. However, these policies raise several legal issues. The
      developing and implementing of institutional ELD-policies are legitimated as such
      and imposing additional criteria or limitations on patients or physicians are
      allowed if all patients' rights are respected. Due to many differences in form
      and content, their legal value is difficult to define. Nevertheless,
      institutional ELD-policies are only enforceable on physicians after incorporation
      into a binding agreement and without violation of their (deontological and/or
      legal) right to professional autonomy. Patients (or their legal representatives)
      can never obligate physicians or health care institutions to comply with
      institutional ELD-policies, unless enforceable patients' rights are violated.

PMID- 20157983
TI  - They shoot horses, don't they? How valid are the arguments of opponents against
      euthanasia?
AB  - In this article the arguments against euthanasia are examined. One of the
      weightiest arguments of mental health professionals against the practice of
      euthanasia is that a doctor's active commitment to euthanasia can be interpreted
      as causing harm. It is investigated whether this statement can be ethically
      justified on the basis of the text of the medical oath or medical declaration.
      Furthermore, it will be discussed whether it is ethically acceptable when doctors
      refuse a) to help candidates of euthanasia who (would likely) meet the legal
      standards of euthanasia, or b) to refer them to a colleague.

PMID- 20157984
TI  - Belgian Act on Euthanasia: alterations to be expected?
AB  - The Belgian 28 May 2002 Act has partially decriminalized euthanasia, i.e.
      intentionally terminating patient's life by a doctor at the individual's request.
      Until now, this Act has not undergone any far-reaching alterations. But it does
      not mean that the status quo applies. The existence of the Act was punctuated by
      different legal developments. The Belgian Constitutional Court made two judgments
      about it. Furthermore, numerous parliamentary bills were proposed in the Senate
      and the House of Representatives in relation with its provisions. If the
      contribution of the Constitutional Court's decisions to the debate on euthanasia
      is limited, in such a way that the Court's intervention does not contain the
      seeds of changes far as the Act on Euthanasia is concerned, the presented bills,
      on the contrary, could presage evolutions of the text.

PMID- 20157985
TI  - Towards an effective definition of death and disorders of consciousness.
AB  - There exists much controversy in providing an effective definition of human
      death, largely due to the lack of a rigorous separation and ordered formulation
      of three distinct elements: a universally accepted definition of death, the
      medical criterion (anatomical substrata) for determining that death has occurred,
      and the tests to prove that the criterion has been satisfied. The papers herein
      review medical standards, philosophical arguments, neurophysiological knowledge,
      behavioural and cognitive theory and the legal ramifications of the brain
      oriented standards of death (whole brain, brainstem and higher brain). The papers
      examine the notion of connectivities and networks of conscious experience in
      order to formulate an effective definition of death, based on the basic
      physiopathological mechanisms of consciousness. We cannot simply differentiate
      and locate arousal as a function of the ascending reticular activating system,
      and awareness as a function of the cerebral cortex. Substantial interconnections
      among the brainstem, subcortical structures, and the neocortex are essential
      integrating components of human consciousness. This paper attempts to reconcile
      the brain-oriented standards that are currently inconsistent. The thread of the
      arguments is the basis for a standard of human death that includes consciousness
      as the most important function of the body, because it provides the capacity for
      integrating the functions of the body. The notion of consciousness as the
      ultimate integrative function is more consistent with the biologically-based
      systems than the more philosophically-based notions of personhood. Both sides of
      the argument are presented herein.

PMID- 20157986
TI  - Networks of conscious experience: computational neuroscience in understanding
      life, death, and consciousness.
AB  - We demonstrate brain locations appearing to correlate with consciousness, but not
      being directly responsible for it. Technology reveals that brain activity is
      associated with consciousness but is not equivalent to it. We examine how
      consciousness occurs at critical levels of complexity. Conventional explanations
      portray consciousness as an emergent property of classical computer-like
      activities in the brain's neural networks. Prevailing views in this camp are that
      patterns of neural network activities correlate with mental states, that
      synchronous network oscillations in the thalamus and cerebral cortex temporally
      bind information, and that consciousness emerges as a novel property of
      computational complexity among neurons. A hard-wired theory is enigmatic for
      explaining consciousness because the nature of subjective experience, or 'qualia'
      'inner life' - is a "hard problem" to understand; binding spatially distributed
      brain activity into unitary objects, and a coherent sense of self, or 'oneness'
      is difficult to explain as is the transition from pre- to conscious states.
      Consciousness is non-computable and involves factors that are neither random nor
      algorithmic - consciousness cannot be simulated; explanations are also needed for
      free will and for subjective time flow. Convention argues that neurons and their
      chemical synapses are the fundamental units of information in the brain, and that
      conscious experience emerges when a critical level of complexity is reached in
      the brain's neural networks. The basic idea is that the mind is a computer
      functioning in the brain. In fitting the brain to a computational view, such
      explanations omit incompatible neurophysiological details, including widespread
      apparent randomness at all levels of neural processes (is it really noise, or
      underlying levels of complexity?); glial cells (which account for some 80% of the
      brain); dendritic-dendritic processing; electrotonic gap junctions;
      cytoplasmic/cytoskeletal activities; living state (the brain is alive!); and
      absence of testable hypotheses in emergence theory. There is no threshold or
      rationale specified; rather, consciousness 'just happens'. Consciousness then
      involves an awareness of what we are sensing or experiencing and some ability to
      control or coordinate voluntary actions. These issues of life, death, and
      consciousness are discussed in the context of Mike, the headless chicken, who
      survived for 18 months, and in the context of consciousness with high degrees of
      intellectual and cognitive function in a congenitally anencephalic brain;
      additionally, in the reanimation work of Soviet scientists in the 1920-30s, and
      in auditory sentence processing in patients in comatose, vegetative, and
      minimally conscious states.

PMID- 20157987
TI  - Brain anatomy, cerebral blood flow, and connectivity in the transition from PVS
      to MCS.
AB  - BACKGROUND: We report a 15 year-old girl with sickle cell disease, who developed
      important cognitive impairment due to multiple strokes, and who had been
      diagnosed with PVS. Nonetheless, when she was later admitted to our Institute,
      according to the presence of inconsistent but clearly demonstrable behavioral
      evidence of consciousness awareness, we changed our diagnosis to MCS. METHODS:
      This patient was studied by T1 MRI images, co-registration of fractional
      anisotropy (FA), and SPECT with MRI. RESULTS: Brain structures were mainly
      preserved in posterior areas of both cerebral hemispheres, although small tissue
      islands were present in both frontal lobes, mainly preserved in the right one.
      SPECT showed CBF preservation in posterior brain regions and in the cerebellum,
      and in those frontal small islands of tissue lateralized to the right frontal
      lobe; meanwhile FA showed preservation of anatomical connectivity among posterior
      and frontal brain regions. These remaining cortical regions are also connected
      with the thalami. CONCLUSION: These results showing connectivity among posterior
      and frontal cortical and probably with other subcortical regions, and CBF
      preservation in these areas, might explain the recovery of minimum awareness
      despite huge anatomical brain lesions.

PMID- 20157988
TI  - Diagnostic value of neurophysiological tests in the diagnosis of brain death--do
      we need changes in national guidelines?
AB  - For a final diagnosis of brain death one needs particular proof that the brain
      has fully stopped functioning. In this respect, diagnostic tests need to be used
      to confirm the clinical findings. Since in different countries there are various
      national guidelines for the determination of brain death, the aim of this study
      is to point to the diagnostic value of electroencephalography (EEG) and evoked
      potentials (EP) in verifying brain death. The need is emphasized for the two
      methods to be used in combination, and, accordingly, for the current national
      guidelines to be changed in our country and also in other countries round the
      world.

PMID- 20157989
TI  - Brain death is not death: a critique of the concept, criterion, and tests of
      brain death.
AB  - This paper suggests that there are insurmountable problems for brain death as a
      criterion of death. The following are argued: (1) brain death does not meet an
      accepted concept of death, and is not the loss of integration of the organism as
      a whole; (2) brain death does not meet the criterion of brain death itself; brain
      death is not the irreversible loss of all critical functions of the entire brain;
      and (3) brain death may, however rarely, be reversible. I conclude that brain
      death, while a devastating neurological state with a dismal prognosis, is not
      death.

PMID- 20157990
TI  - Irreversibility: cardiac death versus brain death.
AB  - The acceptance of brain death (BD) as death of the human being has been
      progressively accepted beginning in the early 1960s. The issue of irreversibility
      is directly related to the diagnosis of human death, and it is closely associated
      with the concept of potentiality, i.e., that some patients still have the
      potentiality of living. In recent years several authors have proposed to use a
      cardiocirculatory criterion for death determination in transplant donors. This
      has aroused ethical and medical controversies regarding concerns to accept that a
      non-heart-beating donor is really dead. We conclude that the cardiocirculatory
      criterion of death only assures irreversibility when asystole is prolonged enough
      to assure that ischemia and anoxia have destroyed the brain. On the contrary, BD
      fulfills both requirements for death determination: cessation of functions and
      irreversibility

PMID- 20157991
TI  - Persistent vegetative and minimally conscious states.
AB  - The diagnosis and management of patients with persistent vegetative (PVS) and
      minimally conscious (MCS) states entail powerful medical, ethical and legal
      debates. The recent description of the MCS highlights the crucial role of
      unexpected and well-documented recoveries of cognitive functions. Functional
      neuroimaging has provided new insights for assessing neuropathology and cerebral
      activity in these patients, providing information on the presence, degree, and
      location of any residual brain function in patients with PVS or MCS. We present a
      review on this topic, emphasizing the clinical and neuroimaging assessment of
      these states, with some of our recent results in this area. We conclude that the
      development of rehabilitation techniques for patients with PVS and others
      suffering long-lasting effects of brain injury is a crucial challenge for actual
      and future generations of neuroscientists.

PMID- 20157992
TI  - The utility of median somatosensory evoked potentials in anoxic-ischemic coma.
AB  - The early recognition of comatose patients with a hopeless prognosis--regardless
      of how aggressively they are managed--is of utmost importance. Median
      somatosensory evoked potentials (SSEP) supplement and enhance neurological
      examination findings in anoxic-ischemic coma and are useful as an early guide in
      predicting outcome. The key finding is that bilateral absence of cortical evoked
      potentials reliably predicts unfavorable outcome in comatose patients after
      cardiac arrest. The author studied 50 comatose patients with preserved brainstem
      function after cardiac arrest. All 23 patients with bilateral absence of cortical
      evoked potentials died without awakening. Neuropathological study in seven
      patients disclosed widespread ischemic changes or frank cortical laminar
      necrosis. The remaining 27 patients with normal or delayed central conduction
      times had an uncertain prognosis because some died without awakening or entered a
      persistent vegetative state. The majority of patients with normal central
      conduction times had a good outcome, whereas a delay in central conduction times
      increased the likelihood of neurological deficit or death. Greater use of SSEP in
      anoxic-ischemic coma would identify those patients unlikely to recover and would
      avoid costly medical care that is to no avail.

PMID- 20157993
TI  - Transcranial magnetic stimulation in disorders of consciousness.
AB  - We have reviewed the literature on transcranial magnetic stimulation studies in
      patients with brain death, coma, vegetative, minimally conscious, and locked-in
      states. Transcranial magnetic stimulation permits non-invasive study of brain
      excitability and may extend our understanding of the underlying mechanisms of
      these disorders. However, use of this technique in severe brain damage remains
      methodologically ill-defined and must be further validated prior to clinical
      application in these challenging patients.

PMID- 20157994
TI  - Recommendations for the use of transcranial Doppler ultrasonography to determine
      the existence of cerebral circulatory arrest as diagnostic support for brain
      death.
AB  - INTRODUCTION: The clinical criteria for brain death consist of the demonstration
      of the absence of any clinical sign of encephalic activity. Confirmatory testing
      is usually not required for the diagnosis of brain death, except in some special
      situations that Spanish law details. In these situations demonstrating cerebral
      circulatory arrest (CCA) by cerebral flow studies is necessary to support the
      diagnosis of brain death. AIM: To review the use of transcranial Doppler
      ultrasonography (TCD) for confirming brain death and to establish uniform
      criteria for the routine use of TCD as a confirmatory test. METHODS: Based on
      literature analysis, the authors developed guidelines for performance and
      interpretation of TCD in clinically brain-dead patients, in order to confirm the
      diagnosis. The active members of the Spanish Neurosonology Society (SONES)
      reviewed an initial draft, until a consensus was reached. RESULTS: In a
      clinically brain-dead patient, specific intracranial flow patterns indicating CCA
      can be visualized by TCD. The specific flow patterns are the presence of
      reverberating flow and/or systolic spikes, and should be detected in both middle
      cerebral arteries and also in the basilar artery. We recommend repeating the
      examination within 30 minutes to confirm the findings. CONCLUSIONS: TCD is a
      useful method for detecting CCA and therefore can be used to confirm brain death
      in a clinically brain-dead patient. The presence of reverberating flow, systolic
      spikes or absence of flow in the basilar and both middle cerebral arteries
      observed in two examinations is highly specific for the prediction of CCA and
      brain death in all patients.

PMID- 20157995
TI  - Induced mild hypothermia in children after brain injury.
AB  - AIM: To determine the safety and effectiveness of mild induced hypothermia in
      children after traumatic or posthypoxic brain injury. Thirteen patients after
      traumatic or poshypoxic brain injury were involved in the study. Mean age was
      11.1 +/- 5.7 years. Median GCS 6 (3-8), PIM2 20.3 +/- 28.2%. RESULTS: GOS 5 was
      assigned for six (46%) patients and GOS 4 for seven (54%) patients. Average GOS
      in patients after severe head trauma was 4.1 points; in patients with posthypoxic
      brain injury 5 points (p < 0.05). No life threatening complications occurred.
      CONCLUSION: Mild induced hypothermia can be safely used in pediatric patients
      after severe traumatic or posthypoxic brain injury. This method may be of benefit
      while improving outcomes in children.

PMID- 20157996
TI  - Transplantation: current developments and future directions.
AB  - An historical overview of transplantation is presented in which the medical,
      legal, ethical, physiological and immunological issues are reviewed in the
      context of the definition of death. A discussion of the benefits of minimal
      immunosuppression is presented as an attractive proposal compared with
      conventional immunosuppression. Prope tolerance was first used with the powerful
      lympholytic monoclonal antibody Campath 1H. The five-year follow-up of the first
      renal transplant patients treated with Campath induction and maintenance low-dose
      cyclosporine has been satisfactory, thus indicating considerable experience of
      the use of induction followed by steroid-free minimal maintenance
      immunosuppression. It appears likely that this will become a favoured method of
      recipient management.

PMID- 20157997
TI  - Death and irreversibility.
AB  - The concept of irreversibility plays a central role in most discussions of how to
      understand and determine human death. This seems to relativize death, since the
      possibilities of reversal will always depend on circumstance. I discuss the
      conceptual problems created by this fact, arguing that their seriousness depends
      on whether we take our conception of death to be a definition or criterion.
      Relativity is probably not fatal in a definition of death; it might even be
      desirable in a policy criterion. The concept of permanence is no less
      philosophically problematic in this context than irreversibility.

PMID- 20157998
TI  - Defining human death: an intersection of bioethics and metaphysics.
AB  - For many years now, bioethicists, physicians, and others in the medical field
      have disagreed concerning how to best define human death. Different theories
      range from the Harvard Criteria of Brain Death, which defines death as the
      cessation of all brain activity, to the Cognitive Criteria, which is based on the
      loss of almost all core mental properties, e.g., memory, self-consciousness,
      moral agency, and the capacity for reason. A middle ground is the Irreversibility
      Standard, which defines death as occurring when the capacity for consciousness is
      forever lost. Given all these different theories, how can we begin to approach
      solving the issue of how to define death? I propose that a necessary starting
      point is discussing an even more fundamental question that properly belongs in
      the philosophical field of metaphysics: we must first address the issue of
      diachronic identity over time, and the persistence conditions of personal
      identity. In this paper, I illustrate the interdependent relationship between
      this metaphysical question and questions concerning the definition of death. I
      also illustrate how it is necessary to antecedently attend to the metaphysical
      issue of defining death before addressing certain issues in medical ethics, e.g.,
      whether it is morally permissible to euthanize patients in persistent vegetative
      states or procure organs from anencephalic infants.

PMID- 20157999
TI  - The political economy of death and the history of its criteria.
AB  - This paper argues for a constitutive link between ecologies of social interests
      and the social receptivity, if not also the formation, of some recent criteria of
      death. It maintains that these criteria have been embraced by ecologies that have
      been dominated by certain economic interests in pronouncing some patients dead.
      Moreover, the very same ecologies have also embraced philosophical
      representations of those criteria, but only such that were able to conceal these
      interests and thereby legitimize and reaffirm their hegemony. Based on this
      observation, the paper concludes that the current criteria of death and their
      philosophical representations are ideological constructs in the strict Marxian
      sense. They may or may not be 'really' true, but they are 'necessarily false' in
      one respect: they owe their social status to the fact that their self-professed
      role-pronouncing dead those who are dead-is not in accord with their objective,
      i.e., social, role-pronouncing dead those who should be dead.

PMID- 20158000
TI  - Israel's new brain-respiratory death act: one step forward or two steps backward?
AB  - Although the legalization of the concept of brain death in Israel may be similar
      to that in other developed countries, much doubt surrounds its wisdom and
      practical effect. The new Israeli act raises theoretical and practical concerns,
      which were not fully anticipated by lawmakers. The article describes the new law
      and elaborates on key issues deriving from the regulation of brain death. Its
      main argument is that the new legislation of brain-respiratory death suffers from
      some major problems that need to be addressed so that it will have some
      meaningful, let alone less detrimental bearing on the acceptance of brain death
      in Israel and the practice of its determination.

PMID- 20158001
TI  - Computer implants and death.
AB  - Although a patient whose whole brain has ceased to function may have his heart,
      lungs, and other organs continue to function if they are connected to the
      appropriate machines, the patient is still dead and the machines can be
      disconnected. In the future, nanotechnology, or other technology, may allow
      putting implants in the brainstem that can keep a patient's heart, lungs and
      other organs functioning, even though the whole natural brain has ceased to
      function. It would be useful to consider how this technology might affect the
      criterion of death before it is actually available.

PMID- 20158002
TI  - Planning and providing for a good death using rural French-Canadian and English
      Canadian insights.
AB  - Little is known about what constitutes a good death, although palliative care is
      broadly aimed at enabling the good death. Good deaths could vary considerably
      across populations. A two-stage ethnographic study was conducted in rural Canada,
      involving English-speaking Albertans and French-Canadians in Quebec, to establish
      a conceptual understanding of the good death from a rural perspective. This study
      identified four common bicultural elements, as well as a conceptual model
      focusing on quality of life through four dimensions: physical, spiritual, social,
      and emotional/psychological. Rurality was identified as a dominant consideration
      for further study.

PMID- 20158003
TI  - Bisphosphonate-related osteonecrosis of the jaws an old disease with a new drug?

PMID- 20158004
TI  - When things are tough, it is time to reflect, [corrected] refocus, and redirect.

PMID- 20158005
TI  - Mandibular open-close motion in children with anterior crossbite occlusion.
AB  - Anterior crossbite (ACB) malocclusions are frequent; however, its characteristic
      functional features have not been fully described. The purpose of this study was
      to determine the characteristics of habitual mandibular open-close motion in
      children with ACB of their primary dentition. Two groups of children were
      selected for study; 17 with ACB (eight boys and nine girls; four years one month
      to seven years one month) and 19 with normal occlusion (eight boys and 11 girls;
      four years six months to six years seven months). The motion was recorded using
      an optoelectronic analysis system with six degrees-of-freedom. Mandibular incisor
      and condylar motion were analyzed by measuring their three-dimensional ranges and
      trajectories. Also estimated incisor and condylar pathways of the two groups were
      compared. Patients with ACB opened wider with more anterior-posterior condylar
      translation and more mandibular rotation. Although between-subject (inter
      individual) variance of all variables in children with ACB was larger, they had
      less within-subject variance at the condyles. These results indicate that open
      close mandibular motion in children with ACB is completely different from that of
      children with normal occlusion. The different motions might be related to
      morphological differences between the two groups.

PMID- 20158006
TI  - Jaw motion during gum-chewing in children with primary dentition.
AB  - This study was undertaken to characterize jaw motion during mastication in
      children with primary dentition and to compare jaw motion with that in adults.
      The means and the variances of the traditional parameters for the chewing cycle,
      i.e., duration, excursive ranges and 3-D distances of travel at the lower
      incisor, molars and condyles were analyzed and compared in 23 children and 25
      female adults. The duration of opening in children was significantly shorter than
      that of adults. Significant differences between children and adults were observed
      in lateral and vertical excursion of the incisor, lateral excursion at the
      molars, and vertical excursion at the condyles. Many of these measurements had
      larger between-subject and between-cycle variances in children than adults,
      suggesting that chewing motion in children has not yet matured. The results of
      this study indicate that chewing motion in children is different from that of
      adults.

PMID- 20158007
TI  - Fixed orthodontic therapy in temporomandibular disorder (TMD) treatment: an
      alternative to intraoral splint.
AB  - This study evaluated the use of a fixed orthodontic appliance in treatment of
      temporomandibular disorder (TMD) compared to the use of an intra-oral splint.
      Fifty (50) adult patients, with confirmed anterior disk displacement with
      reduction in at least one temporomandibular joint (TMJ), were divided into three
      groups: 20 patients treated with AR splint (Group I); 20 patients treated with a
      fixed orthodontic appliance (Group II) and 10 patients who underwent no treatment
      (Control Group). Joint pain, joint noise, muscle pain, and subjective relief were
      evaluated monthly before the treatment began (T0) and for six months thereafter.
      Subjects in Group I and Group II displayed a significant decrease in joint pain
      (p < 0.01) from T2 and in muscle pain from T1 (p < 0.01) to T6. Subjects in Group
      I showed a higher decrease in the frequency of joint noise (p < 0.05) from T1 to
      T6, compared with Group II. At T2 and T3, the patients in Group II reported a
      significantly lower discomfort level associated with the devices than subjects
      treated with the AR splint (p < 0.05). However, at T5 and T6, this observation
      was inverted. The use of a fixed orthodontic appliance seems to be as efficacious
      as the use of an AR maxillary splint in the treatment of joint pain and muscle
      pain, but not in the treatment of joint noise. These results are valid, at least
      for the short-term clinical results (first six months of treatment). Clinical
      implications for long-term use are not clarified by these results.

PMID- 20158008
TI  - The effect of tooth clenching and grinding on anterior temporalis
      electromyographic activity in healthy subjects.
AB  - The aim of this study was to determine the effect of tooth clenching and grinding
      on anterior temporalis electromyographic (EMG) activity. The sample included 30
      healthy subjects with natural dentition and bilateral molar support, 15 with
      bilateral canine guidance and 15 with bilateral group function. An inclusion
      criterion was that subjects have to be free of signs and symptoms of any
      dysfunction of the masticatory system. Bipolar surface electrodes were located on
      the left and right anterior temporalis muscles. EMG activity was recorded during
      the following conditions: A. eccentric grinding from intercuspal position to the
      right lateral edge-to-edge contact position; B. clenching in right edge-to-edge
      lateral contact position; and C. concentric grinding from right lateral edge-to
      edge contact position to intercuspal position. On the working side, EMG activity
      was not significantly different between conditions in both occlusal schemes. On
      the nonworking side, EMG activity was significantly higher during condition C
      than condition B in both occlusal schemes (mixed model with unstructured
      covariance matrix). When comparing by side, EMG activity was significantly higher
      during conditions A and B on the working side than on the nonworking side.
      However, there was no significant difference during condition C. EMG activity was
      significantly lower with canine guidance than group function on the working side
      (in all conditions) as well as during concentric grinding on the nonworking side.
      These results could explain muscular symptoms in the anterior temporalis muscles
      if the subject is experiencing parafunctional habits either while awake and/or
      sleep that exceed the individual's adaptation capability.

PMID- 20158009
TI  - Anterior throat pain syndromes: causes for undiagnosed craniofacial pain.
AB  - It is not uncommon for practitioners who treat craniofacial pain to see patients
      with undiagnosed throat and submandibular pain. Usually, these patients will
      already have been seen by their primary care physician and frequently, several
      others doctors including otolaryngologists, oral and maxillofacial surgeons, and
      even neurologists. Far too often these patients have three common features: 1.
      they have endured multiple expensive diagnostic tests; 2. they have received
      treatment of multiple courses of antibiotics; and 3. no specific diagnosis for
      their pain complaints has been determined and their pain persists. In this
      article, five disorders, Ernest syndrome, Eagle's syndrome, carotid artery
      syndrome, hyoid bone syndrome and superior pharyngeal constrictor syndrome are
      briefly described. All five produce common symptoms, making diagnosis difficult,
      which is often followed by ineffective or no treatment being provided to the
      patient. Diagnostic criteria and suggested treatment modalities are also
      presented.

PMID- 20158010
TI  - Symmetry of horizontal and sagittal condylar path angles: an in vivo study.
AB  - The specific aims of the study were to determine (1) the mean condylar path
      inclination (CP) and Bennett angles (BA) in occlusally healthy dentate subjects
      and (2) whether there was right-left asymmetry of CP and BA. Eccentric movements
      of three mm and five mm from reference positions were recorded for 45 subjects
      using a Cadiax system. The mean right CP angles: 48.8 +/- 8 degrees (three mm)
      and 48.2 +/- 7 degrees (five mm); the mean left CP angles: 48.8 +/- 8 degrees
      (three mm) and 49.5 +/- 70 (5mm) were steeper than suggested means for setting
      articulators. The mean right BA: 7.7 +/- 3 degrees (3mm) and 7.9 +/- 4 degrees
      (five mm); and the mean left BA: 8.1 +/- 4 degrees (three mm) and 8.5 +/- 4
      degrees (five mm) were lower than suggested means for setting articulators.
      Paired-t-tests showed no significant differences between right-left CP and right
      left BA. These results suggest that current recommended average settings for semi
      adjustable articulators for dentate individuals need to be reassessed.

PMID- 20158012
TI  - A response to "The changing treatment paradigm: save the tooth or place the
      implant"--October 2009.

PMID- 20158011
TI  - Synovial chondromatosis of the temporomandibular joint: an asymptomatic case
      report and literature review.
AB  - Synovial chondromatosis of the temporomandibular joint (TMJ) is a rare lesion
      characterized by the presence of loose bodies in the glenoid fossa. Swelling,
      unilateral pain, occlusal changes, clicking, crepitation, deviation, and limited
      mandibular function are the most common characteristics, although this
      combination is not always apparent. Radiopacities of the TMJ should be thoroughly
      investigated as some signals and symptoms may be not present or combined, taking
      months or even years to confirm a diagnosis. A case report is presented here with
      a brief literature review, where surgical removal was the therapy of choice,
      calling attention to the absence of symptoms and some signals, which may mislead
      final diagnosis.

PMID- 20158013
TI  - The delivery of oral healthcare through chain store pharmacies.

PMID- 20158014
TI  - Guidelines for implant abutment selection for partially edentulous patients.
AB  - Dental implant treatments have changed dramatically since the introduction of
      osseointegration in the 1970s. Placement and restoration of dental implants now
      are considered to be a basic, important component of dental practices around the
      world. During the past several decades, there has been a significant increase in
      the number of dental implant manufacturers and implant restorative components
      available for clinicians and dental laboratory technicians treating partially
      edentulous patients. While the increase in components has improved the esthetic
      and functional results obtainable with dental implants, clinicians also have
      reported difficulties and confusion in treatment planning dental implant
      restorations for partially edentulous patients. This article introduces a
      protocol for implant abutment selection in partially edentulous patients
      undergoing dental implant treatment by describing a clinical/laboratory protocol
      for abutment selection in implant dentistry for implant surgeons, restorative
      dentists, and dental laboratory technicians.

PMID- 20158015
TI  - The methods for the generation of smoothness in dental ceramics.
AB  - Occlusal corrections, acidulated phosphate fluoride applications, carbonated
      beverages, or air-powder abrasion procedures can roughen the surface of
      restorations. Once deteriorated, porcelain surfaces need to be repolished. These
      surfaces can be reglazed or polished through various intraoral and extraoral
      polishing kits. Although clinicians often seek studies on the effect of repeated
      firings on coherence between metal and ceramic, the color of the porcelain,
      fluorescence, microstructure, and brightness, only a limited number of studies
      are available in the literature. This article reviews the available literature
      and presents methods for generating a smooth surface and assessing surface
      roughness. It also discusses the differences between glazing and mechanical
      polishing, highlighting the importance of mechanical polishing of dental
      ceramics.

PMID- 20158016
TI  - Mechanism of action of a desensitizing fluoride toothpaste delivering calcium and
      phosphate ingredients in the treatment of dental hypersensitivity. Part III:
      Prevention of dye penetration through dentin vs a calcium- and phosphate-free
      control.
AB  - It is generally accepted that the pain of dental hypersensitivity resulting from
      gum recession is from the movement of fluid within the exposed tubules of dentin,
      causing changes in pressure on the nerve within the pulpal cavity. One method of
      treating hypersensitivity is to occlude the tubules, preventing fluid movement.
      This article discusses the use of a dye penetration technique, which establishes
      this mechanism of action for a desensitizing fluoride toothpaste containing
      calcium and phosphate. Two groups of intact teeth were perfectly sealed with
      enamel paint. Windows 100-micro to 200-micro deep were opened on opposite sides
      of each tooth at the dentin-enamel junction and briefly etched using 20%
      polyacrylic acid. One batch of teeth was treated eight times for 30 mins each
      with a 1:3 slurry of the desensitizing toothpaste and another set with a similar
      slurry prepared from a calcium- and phosphate-free control. A 0.85% aqueous
      solution of acid red fuchsin dye was applied to each window and allowed to dry.
      After a brief rinse, the teeth were sectioned across the windows. Almost no dye
      penetration was seen in teeth treated with the desensitizing toothpaste; however,
      extensive penetration through the dentin was visible in the control-treated
      teeth. The differences in dye penetration for the two sets of teeth were
      significant by both subjective (P < .001) and objective (P < .01) measures.
      Tubule occlusion because of calcium and phosphate ions from the desensitizing
      toothpaste accounts for its tooth desensitizing efficacy.

PMID- 20158017
TI  - Clinical case report: treatment of mild-to-moderate fluorosis with a minimally
      invasive treatment plan.

PMID- 20158018
TI  - An indirect matrix technique for fabrication of fiber-reinforced direct bonded
      anterior bridges.
AB  - This article discusses the use of a fiber-reinforced direct-bonded resin bridge,
      which provides lower treatment costs and requires less time than more
      conventional restorative materials. However, a disadvantage is the short lifespan
      of the prosthesis. This article describes a case report in which this technique
      is applied.

PMID- 20158019
TI  - Evolving implant design. The NobelActive implant: discussion and case
      presentations.
AB  - The design and development of today's dental implants has been an evolving
      process based on scientific research, clinician input, and manufacturers'
      ingenuity. One new addition to the dental implant armamentarium, the NobelActive
      implant, was introduced worldwide by NobelBiocare approximately 2 years ago.
      While many of the design features of the NobelActive implant are found
      individually in other dental implants, the implant's combination of external and
      internal design characteristics provides for unique handling and applications in
      many difficult clinical situations. Although the NobelActive implant can be used
      in most all clinical situations, its design allows for high levels of initial
      stability even in situations with low density or compromised bone, making it a
      good implant choice for immediate extraction, immediate implant placement, and
      immediate load cases, as well as cases with less-than-ideal qualities and
      quantities of bone. In addition, the implant has the ability to be redirected if
      less-than-ideal implant placement occurs at the time of implant insertion,
      maximizing the potential prosthetic outcomes. Prosthetically, the implant has
      features designed to minimize crestal bone loss and maximize gingival
      architecture, while minimizing the prosthetic components and instrumentation.
      This article discusses the characteristics of the NobelActive implant in detail
      and employs case presentations to illustrate its clinical use.

PMID- 20158020
TI  - Multiscale simulation of soft matter systems.
AB  - This paper gives a short introduction to multiscale simulation approaches in soft
      matter science. This paper is based on and extended from a previous review. (1.
      C. Peter and K. Kremer, Soft Matter, 2009, DOI:10.1039/b912027k.) It also
      includes a discussion of aspects of soft matter in general and a short account of
      one of the historically underlying concepts, namely renormalization group theory.
      Some different concepts and several typical problems are shortly addressed,
      including a (more personal) view on challenges and chances.

PMID- 20158021
TI  - Fine-graining without coarse-graining: an easy and fast way to equilibrate dense
      polymer melts.
AB  - A technique to prepare well-equilibrated polymer melts is presented. The method,
      named fine-graining, consists of two steps: the generation of continuum random
      walks characterized by different Kuhn lengths and the insertion of the atomistic
      units on the "parent" random walk chains. The procedure ensures a good
      equilibration at long as well as short length-scales and it is very easy to
      implement. Melts of polyethylene, atactic polystyrene and polyamide-66 are
      equilibrated with this technique and their long and short range structural
      properties can be successfully compared with previous simulation and experimental
      data.

PMID- 20158022
TI  - Systematic coarse-graining of molecular models by the Newton inversion method.
AB  - Systematic construction of coarse-grained molecular models from detailed
      atomistic simulations, and even from ab initio simulations is discussed.
      Atomistic simulations are first performed to extract structural information about
      the system, which is then used to determine effective potentials for a coarse
      grained model of the same system. The statistical-mechanical equations expressing
      the canonical properties in terms of potential parameters can be inverted and
      solved numerically according to the iterative Newton scheme. In our previous
      applications, known as the Inverse Monte Carlo, radial distribution functions
      were inverted to reconstruct pair potential, while in a more general approach the
      targets can be other canonical averages. We have considered several examples of
      coarse-graining; for the united atom water model we suggest an easy way to
      overcome the known problem of high pressure. Further, we have developed coarse
      grained models for L- and D-prolines, dissolved here in an organic solvent
      (dimethylsulfoxide), keeping their enantiomeric properties from the corresponding
      all-atom proline model. Finally, we have revisited the previously developed
      coarse-grained lipid model based on an updated all-atomic force field. We use
      this model in large-scale meso-scale simulations demonstrating spontaneous
      formation of different structures, such as vesicles, micelles, and multi-lamellar
      structures, depending on thermodynamical conditions.

PMID- 20158023
TI  - Mesoscale modelling of polyelectrolyte electrophoresis.
AB  - The electrophoretic behaviour of flexible polyelectrolyte chains ranging from
      single monomers up to long fragments of a hundred repeat units is studied by a
      mesoscopic simulation approach. Abstracting from the atomistic details of the
      polyelectrolyte and the fluid, a coarse-grained molecular dynamics model
      connected to a mesoscopic fluid described by the Lattice-Boltzmann approach is
      used to investigate free-solution electrophoresis. Our study demonstrates the
      importance of hydrodynamic interactions for the electrophoretic motion of
      polyelectrolytes and quantifies the influence of surrounding ions. The length
      dependence of the electrophoretic mobility can be understood by evaluating the
      scaling behavior of the effective charge and the effective friction. The perfect
      agreement of our results with experimental measurements shows that all chemical
      details and fluid structure can be safely neglected, and a suitable coarse
      grained approach can yield an accurate description of the physics of the problem,
      provided that electrostatic and hydrodynamic interactions between all entities in
      the system, i.e., the polyelectrolyte, dissociated counterions, additional salt
      and the solvent, are properly accounted for. Our model is able to bridge the
      single molecule regime of a few nm up to macromolecules with contour lengths of
      more than 100 nm, a length scale that is currently not accessible to atomistic
      simulations.

PMID- 20158024
TI  - Kinetic Monte Carlo simulations of flow-induced nucleation in polymer melts.
AB  - We derive a kinetic Monte Carlo algorithm to simulate flow-induced nucleation in
      polymer melts. The crystallisation kinetics are modified by both stretching and
      orientation of the amorphous chains under flow, which is modelled by a recent non
      linear tube theory. Rotation of the crystallites under flow is modelled by a
      simultaneous Brownian dynamics simulation. Our kinetic Monte Carlo approach is
      highly efficient at simulating nucleation and is tractable even at low under
      cooling. The simulations predict enhanced nucleation under both transient and
      steady state shear. Furthermore the model predicts the growth of shish-like
      elongated nuclei for sufficiently fast flows, which grow by a purely kinetic
      mechanism.

PMID- 20158025
TI  - Simulations of theoretically informed coarse grain models of polymeric systems.
AB  - Simulations of theoretically informed coarse grain models, where the interaction
      energy is given by a functional of the local density, are discussed in the
      context of polymeric melts. Two different implementations are presented by
      addressing two examples. The first relies on a grid-based representation of non
      bonded interactions and focuses on the concept of density multiplication in block
      copolymer lithography. Monte Carlo simulations are used in a high-throughput
      manner to explore the parameter space, and to identify morphologies amenable to
      lithographic fabrication. In the second example, which focuses on the order
      disorder transition of block copolymers, the constraints imposed by a grid are
      removed, thereby enabling simulations in arbitrary ensembles and direct
      calculation of local stresses and free energies.

PMID- 20158026
TI  - A simple coarse-grained model for self-assembling silk-like protein fibers.
AB  - Collagen-silk-collagen triblock polypeptides can self-assemble at low pH into
      nanometer thin fibers with a length in the order of micrometers. Previously we
      predicted, via all-atom simulations, the structure of the folded silk domain to
      be a beta-roll. In this work we develop a simple coarse-grained model of the silk
      domain to enable a numerical study of the fiber's properties and formation on a
      larger length and time scale. As an initial coarse-grained model for the fiber
      forming protein we chose the model of Brown et al., Proc. Natl. Acad Sci. U.S.A.,
      2003, 100, 10712-10717. We adapted this model, and optimized its parameters to
      reproduce the all-atom molecular dynamics simulation structural data. The unknown
      strength of the attraction between the beads representing the residues is
      optimized by computing the Potential of Mean Force for unfolding a strand of the
      beta-roll, using non-equilibrium steered MD simulations in combination with the
      Jarzynski relation. Using these optimized parameters we observed spontaneous
      folding of a short peptide. The coarse-grained beta-roll, as well as a much
      larger stack (a fiber) of beta-rolls, were found to be stable. Moreover, the
      predicted fiber persistence length is in agreement with experiment. The efficacy
      of the mapping of a coarse-grained system onto an all-atom simulation is
      discussed. The approach opens the way for large-scale simulations of fibers,
      based on molecular structure, and allows investigation of their nucleation,
      growth, cross-linking mechanism, network dynamics, and rheology.

PMID- 20158027
TI  - Phase behavior of low-functionality, telechelic star block copolymers.
AB  - We apply state-of-the-art, Grand Canonical Monte Carlo simulations to determine
      the self-organization and phase behavior of solutions of block copolymer stars.
      The latter consist of f AB-block copolymers with N monomers each, which contain a
      solvophilic block A and solvophobic block B, and which are tethered on a common
      center on their A-side. We vary the degree of polymerization N and the relative
      composition of the block copolymer arms and investigate the interplay between
      macrophase and microphase separation in the system. Preliminary results of the
      effect of increasing the number of arms, f of the stars are also presented.

PMID- 20158028
TI  - Mesoscopic modelling of colloids in chiral nematics.
AB  - We present numerical modelling of colloidal particles in chiral nematics with
      cubic symmetry (blue phases) within the framework of the Landau-de Gennes free
      energy. The interaction potential of a single, nano-sized colloidal particle with
      a -1/2 disclination line is calculated as a generic trapping mechanism for
      particles within the cholesteric blue phases. The interaction potential is shown
      to be highly anisotropic and have threefold rotational symmetry. We discuss the
      equilibration of the colloidal texture with respect to particle positions and the
      unit cell size of the blue phase. We also describe how preservation of the liquid
      crystal volume and the number of particles allows blue phase colloidal structures
      with different unit cell sizes and configurations to be compared numerically.

PMID- 20158029
TI  - A molecular level simulation of a twisted nematic cell.
AB  - We have performed a Monte Carlo simulation of a sub-micrometric twisted nematic
      cell with nearly 106 particles using an off-lattice molecular model of a liquid
      crystal. This computer experiment is a proof of principle that molecular models
      can be pushed to the limit of the system sizes addressable with finite element
      models thus bridging the mesoscopic gap for multiscale modelling while providing
      a direct molecular level view of the working of the display. This approach, that
      allows a direct prediction of molecular organisations, properties, and responses
      of device systems without the requirement of prior estimate or knowledge of
      material properties (e.g., elastic constants), is particularly important in view
      of simulating materials and devices for which these quantities are not known.
      Results for the molecular organisation are discussed, with particular regard to
      its helical nature in the field-off state.

PMID- 20158030
TI  - Lyotropic self-assembly mechanism of T-shaped polyphilic molecules.
AB  - We present coarse-grained molecular dynamics simulations of mixtures of a model
      of T-shaped polyphilic bolaamphiphile liquid crystal molecules with a solvent.
      Based on the premise that the most important features of the liquid structure
      stem from the balance between the close range repulsions and the strong
      directional forces typical of hydrogen bonding and association, we have employed
      a coarse-graining approach that simplifies and minimises the attractions present
      in the system. The model consists of six fused rigid spheres, where the two end
      spheres have a significant attraction amongst themselves while the rest are
      repulsive in nature. A weakly self-attracting lateral chain consisting of fully
      flexible tangently bonded spheres is attached to one of the central spheres.
      Thus, the T-shaped molecule is composed of three mutually repulsive segments
      which allow the pure system to self-assemble into a liquid crystalline honeycomb
      columnar phase. The stability of the columnar phase is probed by the sequential
      addition of a solvent that has affinity with only one of the segments of the
      molecule. Our coarse-graining technique allows us to observe dynamically not only
      the 1st level nanoscale segregation but also the 2nd level reorganization which
      leads to the formation of replicated periodic structures. It is seen how this
      latter structuring takes place at times which are an order of magnitude longer
      than the former, and by itself explains the practical limitations of studying
      self-assembly with more detailed atomistic models. Mobility coefficients (related
      to diffusion constants), order parameters and direct visualization of the
      configurations are used to present a phase diagram for the solvated system in the
      whole concentration range. At low solvent density, the solvent solvates the
      honeycomb structure, but does not alter the order significantly. At modest volume
      fractions of solvent, the solvent mostly segregates into a distinct phase, while
      the T-shaped molecules retain a phase with columnar structure. At very large
      solvent concentrations, the T-shaped molecules form structureless aggregates,
      while at the infinite dilution limit present themselves as dimers and monomers.

PMID- 20158031
TI  - Coarse-grained simulations of charge, current and flow in heterogeneous media.
AB  - We present a coarse-grained simulation method for complex charged systems. This
      mesoscopic model couples a hydrodynamic description to a free energy functional
      accounting for the interactions between solvent(s) and charged solutes. It is
      implemented in a hybrid lattice-based algorithm, whereby the evolution of the
      overall mass and momentum is taken care of via a Lattice Boltzmann scheme,
      whereas the composition and ionic concentrations are updated using the link-flux
      method. Several applications illustrate the power of this coarse-grained model
      for charged heterogeneous media: the transport of charged tracers in charged
      porous media, the deformation of an oil droplet in water under the effect of an
      applied electric field, and the distribution of ions at an oil-water interface as
      a function of their affinity for both solvents.

PMID- 20158032
TI  - Multi-particle collision dynamics simulations of sedimenting colloidal
      dispersions in confinement.
AB  - The sedimentation of an initially inhomogeneous distribution of hard-sphere
      colloids confined in a slit is simulated using the multi-particle collision
      dynamics scheme which takes into account hydrodynamic interactions mediated by
      the solvent. This system is an example for soft matter driven out of equilibrium
      where various length and time scales are involved. The initial laterally
      homogeneous density profiles exhibit a hydrodynamic Rayleigh-Taylor-like
      instability. Solvent backflow effects lead to an intricate non-linear behaviour
      which is analyzed via the solvent flow field and the colloidal velocity
      correlation function. Our simulation data are in good agreement with real-space
      microscopy experiments.

PMID- 20158033
TI  - Can the isotropic-smectic transition of colloidal hard rods occur via nucleation
      and growth?
AB  - We investigate the isotropic-to-smectic transformation in a fluid of colloidal
      hard rods using computer simulations. At high supersaturation, we observe
      spinodal decomposition: many small clusters are formed at the initial stage of
      the phase transformation, which form a percolating network that eventually
      transforms into a stable bulk smectic phase. At low supersaturation, we find that
      nucleation and growth of the smectic phase is hampered by the pre-smectic
      ordering in the supersaturated isotropic fluid phase. As the system evolves
      mainly via cooperative motion of these smectic domains, the diffusion and
      attachment of single particles to the nucleation site is largely hindered.

PMID- 20158034
TI  - Multi-scale simulation of asphaltene aggregation and deposition in capillary
      flow.
AB  - Asphaltenes are known as the 'cholesterol' of crude oil. They form nano
      aggregates, precipitate, adhere to surfaces, block rock pores and may alter the
      wetting characteristics of mineral surfaces within the reservoir, hindering oil
      recovery efficiency. Despite a significant research effort, the structure,
      aggregation and deposition of asphaltenes under flowing conditions remain poorly
      understood. For this reason, we have investigated asphaltenes, their aggregation
      and their deposition in capillary flow using multi-scale simulations and
      experiments. At the colloid scale, we use a hybrid simulation approach: for the
      solvent, we used the stochastic rotation dynamics (also known as multi particle
      collision dynamics) simulation method, which provides both hydrodynamics and
      Brownian motion. This is coupled to a coarse-grained MD approach for the
      asphaltene colloids. The colloids interact through a screened Coulomb potential
      with varying well depth epsilon. We tune the flow rate to obtain Pe(flow) >> 1
      (hydrodynamic interactions dominate) and Re << 1 (Stokes flow). Imposing a
      constant pressure drop over the capillary length, we observe that the transient
      solvent flow rate decreases with increasing well depth epsilon. The interactions
      between the mesoscopic asphaltene colloids can be related to atomistic MD
      simulations. Molecular structures for the atomistic calculations were obtained
      using the quantitative molecular representation approach. Using these structures,
      we calculate the potential of mean force (PMF) between pairs of asphaltene
      molecules in an explicit solvent. We obtain a reasonable fit using a -1/r2
      attraction for the attractive tail of the PMF at intermediate distances. We
      speculate that this is due to the two-dimensional nature of the asphaltene
      molecules. Finally, we discuss how we can relate this interaction to the
      mesoscopic colloid aggregate interaction. We assume that the colloidal aggregates
      consist of nano-aggregates. Taking into account observed solvent entrainment
      effects, we deduct the presence of lubrication layers between the nano
      aggregates, which leads to a significant screening of the direct asphaltene
      asphaltene interactions.

PMID- 20158035
TI  - The crossover from single file to Fickian diffusion.
AB  - The crossover from single-file diffusion, where the mean-square displacement
      scales as (x2) to approximately t(1/2), to normal Fickian diffusion, where (x2)
      to approximately t, is studied as a function of channel width for colloidal
      particles. By comparing Brownian dynamics to a hybrid molecular dynamics and
      mesoscopic simulation technique, we can study the effect of hydrodynamic
      interactions on the single file mobility and on the crossover to Fickian
      diffusion for wider channel widths. For disc-like particles with a steep
      interparticle repulsion, the single file mobilities for different particle
      densities are well described by the exactly solvable hard-rod model. This holds
      both for simulations that include hydrodynamics, as well as for those that do
      not. When the single file constraint is lifted, then for particles of diameter
      sigma and pipe of width L such that (L - 2sigma)/sigma = deltac << 1, the
      particles can be described as hopping past one-another in an average time t(hop).
      For shorter times t << t(hop) the particles still exhibit sub-diffusive
      behaviour, but at longer times t >> t(hop), normal Fickian diffusion sets in with
      an effective diffusion constant Dhop to approximately 1/ mean square root of
      t(hop). For the Brownian particles, t(hop) to approximately deltac(-2) when
      deltac << 1, but when hydrodynamic interactions are included, we find a stronger
      dependence than deltac(-2). We attribute this difference to short-range
      lubrication forces that make it more difficult for particles to hop past each
      other in very narrow channels.

PMID- 20158036
TI  - Mori-Zwanzig formalism as a practical computational tool.
AB  - An operational procedure is presented to compute explicitly the different terms
      in the generalized Langevin equation (GLE) for a few relevant variables obtained
      within Mori-Zwanzig formalism. The procedure amounts to introducing an artificial
      controlled parameter which can be tuned in such a way that the so-called
      projected dynamics becomes explicit and the GLE reduces to a Markovian equation.
      The projected dynamics can be realised in practice by introducing constraints,
      and it is shown that the Green-Kubo formulae computed with these dynamics do not
      suffer from the plateau problem. The methodology is illustrated in the example of
      star polymer molecules in a melt using their center of mass as relevant
      variables. Through this example, we show that not only the effective potentials,
      but also the friction forces and the noise play a very important role in the
      dynamics.

PMID- 20158038
TI  - Towards an understanding of membrane-mediated protein-protein interactions.
AB  - We propose a computational framework to study the lipid-mediated clustering of
      integral membrane proteins. Our method employs a hierarchical approach. The
      potential of mean force (PMF) of two interacting proteins is computed under a
      coarse-grained 3-D model that successfully describes the structural properties of
      reconstituted lipid bilayers of dymiristoylphophatidylcholine (DMPC) molecules.
      Subsequently, a 2-D model is adopted, where proteins represented as self-avoiding
      disks interact through the previously computed PMF, which is modified to take
      into account three body corrections. The aggregation of the proteins is
      extensively studied under the condition of negative hydrophobic mismatch: the
      formation of clusters with increasing size agrees with previous computational and
      experimental findings.

PMID- 20158037
TI  - Hierarchical coarse-graining strategy for protein-membrane systems to access
      mesoscopic scales.
AB  - An overall multiscale simulation strategy for large scale coarse-grain
      simulations of membrane protein systems is presented. The protein is modeled as a
      heterogeneous elastic network, while the lipids are modeled using the hybrid
      analytic-systematic (HAS) methodology, where in both cases atomistic level
      information obtained from molecular dynamics simulation is used to parameterize
      the model. A feature of this approach is that from the outset liposome length
      scales are employed in the simulation (i.e., on the order of 1/2 a million lipids
      plus protein). A route to develop highly coarse-grained models from molecular
      scale information is proposed and results for N-BAR domain protein remodeling of
      a liposome are presented.

PMID- 20158039
TI  - Measuring excess free energies of self-assembled membrane structures.
AB  - Using computer simulation of a solvent-free, coarse-grained model for amphiphilic
      membranes, we study the excess free energy of hourglass-shaped connections (i.e.,
      stalks) between two apposed bilayer membranes. In order to calculate the free
      energy by simulation in the canonical ensemble, we reversibly transfer two
      apposed bilayers into a configuration with a stalk in three steps. First, we
      gradually replace the intermolecular interactions by an external, ordering field.
      The latter is chosen such that the structure of the non-interacting system in
      this field closely resembles the structure of the original, interacting system in
      the absence of the external field. The absence of structural changes along this
      path suggests that it is reversible; a fact which is confirmed by expanded
      ensemble simulations. Second, the external, ordering field is changed as to
      transform the non-interacting system from the apposed bilayer structure to two
      bilayers connected by a stalk. The final external field is chosen such that the
      structure of the non-interacting system resembles the structure of the stalk in
      the interacting system without a field. On the third branch of the transformation
      path, we reversibly replace the external, ordering field by non-bonded
      interactions. Using expanded-ensemble techniques, the free energy change along
      this reversible path can be obtained with an accuracy of 10(-3)k(B)T per molecule
      in the n VT-ensemble. Calculating the chemical potential, we obtain the free
      energy of a stalk in the grandcanonical ensemble, and employing semi
      grandcanonical techniques, we calculate the change of the excess free energy upon
      altering the molecular architecture. This computational strategy can be applied
      to compute the free energy of self-assembled phases in lipid and copolymer
      systems, and the excess free energy of defects or interfaces.

PMID- 20158040
TI  - Lateral pressure profiles in lipid monolayers.
AB  - We have used molecular dynamics simulations with coarse-grained and atomistic
      models to study the lateral pressure profiles in lipid monolayers. We first
      consider simple oillair and oil/water interfaces, and then proceed to lipid
      monolayers at air/water and oil/water interfaces. The results are qualitatively
      similar in both atomistic and coarse-grained models. The lateral pressure profile
      in a monolayer is characterized by a headgroup/water pressure-interfacial tension
      chain pressure pattern. In contrast to lipid bilayers, the pressure decreases
      towards the chain free ends. An additional chain/air tension peak is present in
      monolayers at the air/water interface. Lateral pressure profiles are calculated
      for monolayers of different lipid composition under varying surface tension.
      Increasing the surface tension suppresses both pressure peaks and widens the
      interfacial tension in monolayers at the oil/water interface, and mainly
      suppresses the chain pressure in monolayers at the air/water interface. In
      monolayers in the liquid-condensed phase, the pressure peaks split due to
      ordering. Variation of lipid composition leads to noticeable changes in all
      regions of the pressure profile at a fixed surface tension.

PMID- 20158041
TI  - Concerted diffusion of lipids in raft-like membranes.
AB  - Currently, there is no comprehensive model for the dynamics of cellular
      membranes. The understanding of even the basic dynamic processes, such as lateral
      diffusion of lipids, is still quite limited. Recent studies of one-component
      membrane systems have shown that instead of single-particle motions, the lateral
      diffusion is driven by a more complex, concerted mechanism for lipid diffusion
      (E. Falck et al., J. Am. Chem. Soc., 2008, 130, 44-45), where a lipid and its
      neighbors move in unison in terms of loosely defined clusters. In this work, we
      extend the previous study by considering the concerted lipid diffusion phenomena
      in many-component raft-like membranes. This nature of diffusion phenomena emerge
      in all the cases we have considered, including both atom-scale simulations of
      lateral diffusion within rafts and coarse-grained MARTINI simulations of
      diffusion in membranes characterized by coexistence of raft and non-raft domains.
      The data allows us to identify characteristic time scales for the concerted lipid
      motions, which turn out to range from hundreds of nanoseconds to several
      microseconds. Further, we characterize typical length scales associated with the
      correlated lipid diffusion patterns and find them to be about 10 nm, or even
      larger if weak correlations are taken into account. Finally, the concerted nature
      of lipid motions is also found in dissipative particle dynamics simulations of
      lipid membranes, clarifying the role of hydrodynamics (local momentum
      conservation) in membrane diffusion phenomena.

PMID- 20158042
TI  - Membrane poration by antimicrobial peptides combining atomistic and coarse
      grained descriptions.
AB  - Antimicrobial peptides (AMPs) comprise a large family of peptides that include
      small cationic peptides, such as magainins, which permeabilize lipid membranes.
      Previous atomistic level simulations of magainin-H2 peptides show that they act
      by forming toroidal transmembrane pores. However, due to the atomistic level of
      description, these simulations were necessarily limited to small system sizes and
      sub-microsecond time scales. Here, we study the long-time relaxation properties
      of these pores by evolving the systems using a coarse-grain (CG) description. The
      disordered nature and the topology of the atomistic pores are maintained at the
      CG level. The peptides sample different orientations but at any given time, only
      a few peptides insert into the pore. Key states observed at the CG level are
      subsequently back-transformed to the atomistic level using a resolution
      transformation protocol. The configurations sampled at the CG level are stable in
      the atomistic simulation. The effect of helicity on pore stability is
      investigated at the CG level and we find that partial helicity is required to
      form stable pores. We also show that the current CG scheme can be used to study
      spontaneous poration by magainin-H2 peptides. Overall, our simulations provide a
      multi-scale view of a fundamental biophysical membrane process involving a
      complex interplay between peptides and lipids.

PMID- 20158043
TI  - Glutamate-conjugated liposomes of dopamine hydrochloride for effective management
      of parkinsonism's.
AB  - The blood-brain barrier restricts the brain uptake of many important hydrophilic
      drugs and limits their efficacy in the treatment of brain diseases because of the
      presence of tight junctions, high metabolic capacity, low pinocytic vesicular
      traffic, and efficient efflux mechanisms. In the present project, amino acid
      coupled liposomes bearing dopamine HCl were prepared to deliver the drug to the
      brain utilizing receptor-mediated transcytosis. Uncoupled liposomes were prepared
      by cast film method using phosphatidylcholine and cholesterol, whereas coupled
      liposomes were prepared using phosphatidylcholine, cholesterol, and glutamate
      stearylamine conjugate in the film. These liposomes were characterized for
      entrapment efficiency, vesicle size, shape, in vitro drug release, and in vivo
      studies. The in vitro drug release was analysed by using dialysis membrane. The
      vesicle size was found to increase upon coupling of liposomes, whereas percent
      entrapment efficiency was reduced from 38.89 +/- 1.94% to 34.15 +/- 1.70% after
      coupling of liposomes. The in vitro percent cumulative drug release studies
      exhibited 51.6% drug release for uncoupled liposome and 37.9% for coupled
      liposome at the end of 24 h. These selected formulations were subjected for in
      vivo performance, which was assessed by periodic measurement of drug
      (chlorpromazine)-induced catatonia in albino rats (Wistar strain) and
      fluorescence microscopy studies of the rat brain. The results were compared with
      plain dopamine HCl solution. Studies revealed that dopamine HCl can be
      effectively delivered to brain via glutamate-coupled liposomes, and results
      clearly indicated the superiority of the coupled liposomal formulation over the
      uncoupled formulation.

PMID- 20158045
TI  - Study on the intestinal absorption profiles of tanshinone IIA and its inclusion
      complex with cyclodextrin in rats.
AB  - In this paper, the effect of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on
      the intestinal permeability of the tanshinone IIA (TS) was investigated. The
      inclusion complex was obtained at the molar ratio of 1:1 by lyophilization and
      characterized by differential scanning calorimetry and phase solubility studies.
      Using the in situ intestinal perfusion technique, the absorption behaviors of TS
      and its inclusion complex were investigated at a series of concentration levels
      in three separate segments of the small intestine. Using the perfusion model, it
      was demonstrated that the absorption of TS, whether it was free or complexed, was
      independent of both the concentration and the intestinal site. The permeability
      rates of TS across the intestinal epithelial membrane were enhanced about 7 times
      and the fraction absorbed was increased approximately 9-fold by the formation of
      the inclusion complex with HP-beta-CD at each intestinal segment. By measuring
      the permeability results of Lucifer yellow, we propose that the increased
      permeability across intestinal membrane by HP-beta-CD plays an important role in
      enhanced TS absorption. Meanwhile, the morphological studies using HP-beta-CD did
      not reveal significant tissue damage in any of the intestinal segments. The
      results obtained support the use of HP-beta-CD to improve the gastrointestinal
      tract absorption of TS.

PMID- 20158046
TI  - Development of novel bioadhesive buccal formulation of diltiazem: in vitro and in
      vivo characterization.
AB  - The aim of the investigation was to develop and evaluate buccoadhesive tablets of
      diltiazem hydrochloride (DZH) using hydroxypropyl methyl cellulose (HPMC) K4M and
      Carbopol 934 as mucoadhesive polymers. Formulations A1, A2, A3, A4, and B1, B2,
      and B3, were composed of HPMC K4M and Carbopol 934 at ratios of 1:2, 1:3, 1:4,
      1:5, and 1:1, 1:2, 1:3, respectively. The developed formulations were evaluated
      for physicochemical, in vitro drug release, in vitro adhesion and in vivo studies
      in healthy human volunteers. The buccal absorption study in healthy volunteers
      revealed that about 36.86% of the drug was absorbed. Formulation A3 showed
      maximum release in 8 h. As the concentration of polymer in the formulation
      increased, the drug release decreased. The bioavailability of diltiazem from
      buccoadhesive tablets was 1.57-fold higher than oral tablets. The basic
      pharmacokinetic parameters, C(Max), T(Max), and the area under the curve, were
      calculated and showed statistically significant difference (P < 0.05) when the
      drug was given by the buccal route compared to that of oral tablet. The results
      indicate that suitable bioadhesive buccal tablets with improved bioavailability
      could be prepared.

PMID- 20158044
TI  - Preparation, characterization, and in vivo pharmacodynamic evaluation of
      parenteral diclofenac submicron lipid emulsions.
AB  - The aim of the present study was to develop stable parenteral submicron lipid
      emulsions (SLEs) for sustained delivery of diclofenac acid, used to treat
      arthritic conditions, to minimize dosing frequency. The SLEs of diclofenac acid
      were prepared using soybean oil, egg lecithin, and cholesterol. They were heated
      and processed by homogenization and ultrasonication. The influence of formulation
      variables, such as the change in proportion of oil and cholesterol, were studied,
      and optimized formulations were developed. The stability of the optimized
      formulations SM-A (no cholesterol), SM-I (0.05% cholesterol), and SM-II (0.1%
      cholesterol) was studied during autoclaving, centrifugal stress, desorption
      stress (dilution effect), and on storage. The creaming volume percentage was
      found during the storage and centrifugal stress studies. The effect of dilution
      on zeta potential and size was noted in the desorption studies. The total drug
      content and entrapment efficiency was determined using high-performance liquid
      chromatography. In vitro release studies were performed in phosphate buffer using
      dialysis method for 12 h. The in vivo anti-inflammatory activity (reduction in
      paw volume of optimized SLEs) was tested in a 1% carrageenan-induced rat paw
      oedema model and compared with a diclofenac injection (Voveran). Stable SLEs of
      diclofenac were developed with a mean size ranging from 200-250 nm and a zeta
      potential of -31 +/- 1 mV. The cholesterol concentration did not significantly
      affect the prepared SLEs' size and zeta potential. The optimized formulations, SM
      A, SM-I, and SM-II, were relatively stable during centrifugal stress, dilution
      stress, and storage. The drug content was found to be 2.45 +/- 0.26 mg/mL for SM
      A, 2.46 +/- 0.34 mg/mL for SM-I, and 2.42 +/- 0.01 mg/mL for SM-II. The
      entrapment efficiency was 98.91 +/- 0.13%, 99.01 +/- 0.12%, and 99.27 +/- 0.1%
      for SM-A, SM-I and SM-II, respectively. The in vitro drug release was zero-order
      and the cumulative amount of drug released within 12 h was 80% (SM-A), 57% (SM
      I), and 42% (SM-II. During in vivo studies, the optimized formulations initially
      revealed a sustained anti-inflammatory activity occurring up to 12 h, with a
      maximum activity occurring after 2 h. In the case of the diclofenac injection,
      the maximum activity persisted up to 5 h and then gradually decreased. No such
      decrease was noticed regarding the optimized formulations for a period extending
      up to 12 h. Beyond 12 h, activity persisted up to 24 h with a slight reduction in
      effect.

PMID- 20158047
TI  - The effect of stealth liposomes on pharmacokinetics, tissue distribution and anti
      tumor activity of oridonin.
AB  - High-purity oridonin was isolated and identified from Rabdosia rubescens hemsl by
      preparative high-performance liquid chromatography (HPLC). Stealth liposomes of
      oridonin were prepared by thin-film ultrasonic dispersion using polyethylene
      glycol-distearoylphosphatidyleth-anolamine(PEG2000-DSPE) as the surface-coating
      material. A reversed-phase HPLC method was developed and validated to determine
      the concentrations of oridonin in the serum and tissues of mice. The tissue
      distribution and pharmacokinetics of oridonin stealth liposomes and oridonin
      solution in mice were investigated. The results showed that the distribution and
      pharmacokinetics of oridonin stealth liposomes in mice were changed as compared
      to the distribution and pharmacokinetics of oridonin solution. The levels of
      stealth liposomal oridonin in the heart tissues were reduced, while the levels of
      stealth liposomal oridonin in the blood were increased. The stealth liposomes
      were very effective at inhibiting the rate of solid tumor growth. The PEG2000
      DSPE of liposomes prolonged the circulation time of oridonin in mouse blood,
      reduced accumulation in the reticuloendothelial system and increased the anti
      tumor activity of oridonin.

PMID- 20158048
TI  - Loading of propranolol-H+ onto SP Sephadex C-25 studied by isothermal calorimetry
      and spectroscopy.
AB  - The exchange reaction between sulfopropyl-dextran (Sephadex C-25) and propranolol
      hydrochloride (prop-HCl) as a model drug was studied. Binding experiments were
      carried out using a dissolution tester and photometric quantification of the
      amount of drug bound. The thermodynamic parameters of the binding reaction were
      derived by isothermal titration calorimetry (ITC) and equilibrium studies.
      Equilibrium was reached within approximately 12 min and was nicely described by
      the Langmuir equation for low degree of occupation of binding sites
      (concentrations of prop-HCl in equilibrium up to 3.6 mmol/L) with respect to the
      exchange capacity (2.0 mmol/g ion exchanger). However, the heat effects measured
      in the ITC experiment for step-wise addition of drug solution surprisingly
      increased for the first injections up to a maximum and only thereafter decreased.
      The heat effects do not exclusively represent the exchange reaction, but rather
      include a more complex pattern of reactions: shrinking of SP Sephadex C-25 upon
      addition of prop-HCl solution squeezes considerable amounts of the drug molecules
      out of the complex. Although the Langmuir fit is excellent, it cannot reveal
      information about the equilibrium.

PMID- 20158049
TI  - Development and evaluation of transdermal patches of celecoxib.
AB  - Low-dose, matrix-type transdermal patches containing celecoxib were developed for
      the treatment of osteoarthritis. The patches were designed to be used over a
      period of 24 h. Different ratios of ethyl cellulose/polyvinyl pyrrollidone
      (EC/PVP) were used for the development of the system. All of the prepared patches
      were subjected to physicochemical evaluation, in vitro drug release, permeation,
      and anti-inflammatory studies (in vivo). The release rates and flux increased
      linearly when an increase in the fraction of PVP was mixed with the formulations.
      In vitro studies showed enhanced performance in the presence of an enhancer (5%
      v/v oleic acid). The cumulative amount of drug permeated was found to be
      proportional to the square root of time (following the Higuchi equation). The
      anti-inflammatory effect (in vivo) and sustained action were studied by a
      carrageenan-induced (1% w/v) rat hind paw edema method. The selected formulation
      (EC/PVP, 2:3) produced 100% inhibition of paw edema in rats up to 6 h after
      receiving the carrageenan injection. The inhibition was 94.42%, 89.77%, and
      86.44% after 8, 12 and 24 h, respectively. From this study it can be concluded
      that celecoxib can be formulated into a patch for transdermal delivery.
      Therefore, celecoxib can be recommended for further pharmacokinetic and
      pharmacodynamic studies in suitable animal models.

PMID- 20158050
TI  - Validation of a microbiological method using Acholeplasma laidlawii for assessing
      performance of microporous membranes for mycoplasma clearance.
AB  - While no recognized industry standard currently exists for mycoplasma clearance
      testing of membrane filters, several methods have been used by membrane
      manufacturers and contract test laboratories. This validation exercise documents
      one approach to mycoplasma clearance testing and incorporates validation
      guidelines recognized in the biopharmaceutical industry today. The benefits of
      this method are (1) the consistent production of small monodisperse cells, 0.37 x
      0.41 microm, at titers in excess of 1 x 10(9) CFU mL(-1) within 20-24 h of
      incubation; (2) the consistent detection of low levels of Acholeplasma laidlawii
      with an absence of false negative results; and (3) the ability to distinguish
      among membrane filters with different bubble points. The results of the
      validation exercise demonstrate that the equipment, materials, and test methods
      of the A. laidlawii filter challenge test are suitably understood and in a state
      of control. This method is appropriate to characterize the performance of
      membrane filters used in biopharmaceutical applications.

PMID- 20158051
TI  - Practical application of the cake-complete, pore-plugging model for sizing normal
      flow filters.
AB  - Considerable process development efforts are spent selecting and sizing normal
      flow filters-typically beginning with small-scale experiments on flat sheet
      membrane samples and then scaling up to pleated membrane capsules and cartridges.
      Experimentally measuring filter capacity requires long test times; therefore,
      many scientists perform a short, small-scale test and fit the data to a
      mechanistic model which is used to extrapolate the filter's capacity. For more
      than a decade, the most commonly used fouling model has been the standard (or
      gradual pore-plugging) model. In 2006, Bolton et al. proposed a new model which
      combined both cake formation and complete pore-plugging (the "cake-complete"
      model). The authors used this model to fit data sets generated under constant
      flow and constant pressure conditions on microporous and ultrafiltration
      membranes. They concluded that the new model could more consistently predict
      filter performance as it was able to provide good fits of all data sets over a
      wide range of plugging behavior. This work describes a reliable method for
      solving the constant flow and constant pressure forms of the cake-complete model
      and for predicting the initial values of the plugging constants. Additionally,
      algorithms for determining required filter area to satisfy process conditions
      (batch volume and batch time) are proposed.

PMID- 20158052
TI  - Vacuum decay container/closure integrity testing technology. Part 1. ASTM F2338
      09 precision and bias studies.
AB  - ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in
      Packages by Vacuum Decay Method is applicable for leak-testing rigid and semi
      rigid non-lidded trays; trays or cups sealed with porous barrier lidding
      materials; rigid, nonporous packages; and flexible, nonporous packages. Part 1 of
      this series describes the precision and bias studies performed in 2008 to expand
      this method's scope to include rigid, nonporous packages completely or partially
      filled with liquid. Round robin tests using three VeriPac 325/LV vacuum decay
      leak testers (Packaging Technologies & Inspection, LLC, Tuckahoe, NY) were
      performed at three test sites. Test packages were 1-mL glass syringes. Positive
      controls had laser-drilled holes in the barrel ranging from about 5 to 15 microm
      in nominal diameter. Two different leak tests methods were performed at each
      site: a "gas leak test" performed at 250 mbar (absolute) and a "liquid leak test"
      performed at about 1 mbar (absolute). The gas leak test was used to test empty,
      air-filled syringes. All defects with holes > or = 5.0 microm and all no-defect
      controls were correctly identified. The only false negative result was attributed
      to a single syringe with a < 5.0-microm hole. Tests performed using a calibrated
      air leak supported a 0.10-cm3 x min(-1) (ccm) sensitivity limit (99/99 lower
      tolerance limit). The liquid leak test was used to test both empty, air-filled
      syringes and water-filled syringes. Test results were 100% accurate for all empty
      and water-filled syringes, both without holes and with holes (5, 10, and 15
      microm). Tests performed using calibrated air flow leaks of 0, 0.05, and 0.10 ccm
      were also 100% accurate; data supported a 0.10-ccm sensitivity limit (99/99 lower
      tolerance limit). Quantitative differential pressure results strongly correlated
      to hole size using either liquid or gas vacuum decay leak tests. The higher
      vacuum liquid leak test gave noticeably higher pressure readings when water was
      present in the defect. Both the ASTM F2338-09 test method and the precision and
      bias study report are available by contacting ASTM International in West
      Conshohocken, PA, USA (www.astm.org).

PMID- 20158053
TI  - Vacuum decay container/closure integrity testing technology. Part 2. Comparison
      to dye ingress tests.
AB  - Part 1 of this series demonstrated that a container closure integrity test
      performed according to ASTM F2338-09 Standard Test Method for Nondestructive
      Detection of Leaks in Packages by Vacuum Decay Method using a VeriPac 325/LV
      vacuum decay leak tester by Packaging Technologies & Inspection, LLC (PTI) is
      capable of detecting leaks > or = 5.0 microm (nominal diameter) in rigid,
      nonporous package systems, such as prefilled glass syringes. The current study
      compared USP, Ph.Eur. and ISO dye ingress integrity test methods to PTI's vacuum
      decay technology for the detection of these same 5-, 10-, and 15-microm laser
      drilled hole defects in 1-mL glass prefilled syringes. The study was performed at
      three test sites using several inspectors and a variety of inspection conditions.
      No standard dye ingress method was found to reliably identify all holed syringes.
      Modifications to these standard dye tests' challenge conditions increased the
      potential for dye ingress, and adjustments to the visual inspection environment
      improved dye ingress detection. However, the risk of false positive test results
      with dye ingress tests remained. In contrast, the nondestructive vacuum decay
      leak test method reliably identified syringes with holes > or = 5.0 microm.

PMID- 20158054
TI  - Effect of curing cycle on the tensile strength of the bond between heat cured
      denture base acrylic resin and acrylic resin denture teeth.
AB  - The effect of different curing cycles on the tensile strength of the bond between
      one brand of cross-linked acrylic resin teeth and three heat cured denture base
      acrylic resins was tested. There were differences in the tensile bond strength
      between the three heat cured denture base acrylic resins and the three curing
      cycles used. The bond strength of the acrylic resin denture base material made by
      the same manufacturer as the cross-linked acrylic resin denture teeth was higher.
      The bond strength following the short cycle was lowest in all cases, individual
      differences between curing cycles failed to reach statistical significance.

PMID- 20158055
TI  - A report on the clinical and radiographic outcomes of 38 cases of apexification
      with mineral trioxide aggregate.
AB  - The aim of the study was to report on the clinical and radiographic assessment of
      38 cases of apexification using MTA over a three year period. Thirty-eight cases
      of immaturely developed teeth requiring endodontic therapy were treated using MTA
      to achieve an apical barrier prior to obturation with gutta-percha. The teeth
      were clinically and radiographically assessed. The findings indicate that
      apexification using MTA is a predictable procedure. In particular, the number of
      visits and the total time taken to achieve an apical barrier was markedly less
      than conventional techniques using calcium hydroxide. The presence of a
      preoperative periapical radiolucency had no effect on the outcome. MTA shows
      promise as a viable alternative to calcium hydroxide to achieve root-end closure
      and using MTA, the number of visits to achieve a successful apical barrier may be
      markedly reduced. The presence of preoperative periapical radiolucencies did not
      affect the outcome or the treatment protocol.

PMID- 20158056
TI  - Biomechanical behaviour of tooth-supported fixed partial dentures by 3D FEA.
AB  - This three-dimensional finite element analysis first described stresses
      distribution in loaded posterior fixed partial dentures, then compared the
      influences of bone height, abutment roots number and pontic length on their
      displacements. Twelve mandibular (three to five unit) FDPs integrating
      periodontal ligaments were designed. Stresses were localized in connectors and
      cervical areas of abutments near the edentulous span. The main FDPs'
      displacements consisted of vertical translation increasing with low bone height.
      FDPs underwent simultaneously an anteroposterior displacement (about ten times
      smaller) towards the weakest abutment side. Splinted abutments affected this
      anteroposterior displacement. Span length was associated with small beam
      deflection.

PMID- 20158057
TI  - The York consensus statement on implant-supported overdentures.
AB  - The annual Conference of the BSSPD (British Society for the Study of Prosthetic
      Dentistry) was held in York on April 6th and 7th 2009. At the symposium on
      Mandibular Overdentures, presenters offered a synopsis of the research available
      on the efficacy of implant-supported mandibular overdentures in the edentulous
      mandible. Emphasis was given to both qualitative and quantitative research based
      on patient-centred outcomes of treatment. A draft consensus was circulated to all
      presenters and to the Council members of the BSSPD and to BSSPD Members on the
      Society's Website. The statement was modified in the light of their comments,
      audience feedback following the presentations and members' feedback. We hope that
      this consensus statement will be a useful guide for patients and clinicians and
      that it will act to stimulate wider debate. We also hope that it will prove
      useful to other patient and professional organisations and will inform
      discussions with providers of national health care and with independent funders.

PMID- 20158058
TI  - A study in vitro to compare home and surgery vital bleaching techniques.
AB  - The aim of this study was to compare the effectiveness of three different types
      of commonly used bleaching techniques using an in-vitro model. Five groups of 10
      tooth specimens were prepared and allocated randomly to treatment groups. The
      four treatment groups tested were a home tray bleaching product, an 'in surgery'
      tray bleaching product and an 'in surgery power bleaching' product for use with
      an activating light. The bleaching agent in the latter group was also tested
      without light activation to assess the additional benefit of the bleaching lamp.
      A placebo group treated with water was also included. Colour change was assessed
      using a Vita shade guide and an electronic chromometer. The mean change in shade
      guide units ranged from 10.9 to 13.2 units, with the 'in surgery' tray bleaching
      system producing the largest change. For the chromometer readings the mean change
      in tooth colour ranged from 3.6 to 25.6 units, with the night guard vital
      bleaching product producing the largest change. This study has demonstrated in
      vitro that all the different bleaching systems tested produced comparable changes
      in tooth colour.

PMID- 20158059
TI  - Restoring function and aesthetics in a patient previously treated for
      amelogenesis imperfecta.
AB  - A 26-year-old male patient presented with generalised gingival recession related
      to the margins of crowns fitted between the ages of 12 and 15 years. The patient,
      previously treated for Amelogenesis Imperfecta, suffered a mandibular fracture at
      the age of 22 years. He had an anterior open bite and in the retruded contact
      position the 28 and 38 were the only teeth in contact. This case demonstrates the
      management of compromised fixed prosthodontic care following further growth and
      trauma. On completion of treatment a good functional and aesthetic result was
      achieved.

PMID- 20158060
TI  - Patients' ranking of interdental "black triangles" against other common aesthetic
      problems.
AB  - The purpose of this study is to assess patients' aesthetic perceptions of
      interdental "black triangles", both in terms of the number of triangles visible
      and their severity; and to ascertain how patients rank the presence of "black
      triangles" against other aesthetic problems. It is based on a questionnaire of 80
      randomly selected individuals who were asked to rate the aesthetics of digitally
      manipulated images. Patients'perceptions of interdental "black triangles" were
      compared with their perceptions of other 'non-aesthetic' features. Interdental
      "black triangles" were rated as the third most disliked aesthetic problem below
      caries and crown margins. This study demonstrates the importance of interdental
      "black triangles" to patients, and therefore, as they can occur during prosthetic
      treatment, must be discussed with patients prior to commencing therapy.

PMID- 20158061
TI  - Trends in dental education in the Persian Gulf--an example from Iran:
      contemporary placement of posterior composites.
AB  - In recent years, there has been expansion of dental education programmes from
      established European and North American schools into regions in the Middle East,
      the Persian Gulf States, and Asia. Accompanying this, there has been migration of
      dentists from these regions of the world to Europe and North America in the hope
      of finding employment or to pursue postgraduate education. Little awareness
      exists, however in western countries on the amount and level of clinical training
      provided in dental schools in which these dentists have trained. The aim of this
      paper is to investigate the teaching to undergraduate students in Iran of an
      important aspect of clinical dentistry which is showing continual development in
      western schools, namely the use of resin-based composites in the restoration of
      posterior teeth. In 2008, a questionnaire seeking information on the teaching of
      posterior resin-based composites was distributed by email to the person
      responsible for delivering teaching of operative dentistry in each of the 18
      dental schools with undergraduate dental degree programmes in Iran. All 18
      schools teach the placement of occlusal and occlusoproximal resin-based composite
      restorations in premolar and permanent molar teeth. Resin-based composites
      currently account for 42% of posterior direct restorations placed by
      undergraduates in Iran. Despite variations between dental schools being noted in
      the teaching of certain techniques for posterior resin-based composites, the
      overall extent and content of teaching of posterior resin-based composites in
      Iran could be described as comparable to that observed in western countries.

PMID- 20158062
TI  - Implant overdenture using Konus telescope on one-piece implant: a case report.
AB  - An implant-retained Konus (tapered double crown) telescopic complete overdenture
      was fabricated for a mandibular edentulous patient. The Konus telescopic
      overdenture coping crowns and framework assembly were cast with commercially pure
      (CP) titanium, joined using laser welding and placed on four one-piece implants.
      Sufficient retention and stability were obtained using this method.

PMID- 20158063
TI  - Senate works to pass health care reform bill: cuts to home health and Medicare at
      large remain contentious.

PMID- 20158064
TI  - Val J. Halamandaris makes case for home care on C-SPAN.

PMID- 20158065
TI  - NAHC's 28th Annual Meeting & Exposition.

PMID- 20158066
TI  - Making life matter.

PMID- 20158067
TI  - Reducing the risk of falls in the home.

PMID- 20158068
TI  - The benefits of CRM: is your home care agency missing out?
AB  - Home care executives today have at their disposal all the means necessary to
      manage information and strengthen relationships with customers, thanks to
      innovative customer relationship management (CRM) tools, Adam D. Bishop explains.

PMID- 20158069
TI  - Time for random acts of service!

PMID- 20158071
TI  - The collector of Bedford Street.

PMID- 20158070
TI  - Keeping score helps a business reach success.

PMID- 20158072
TI  - [Laparoscopic radical prostatectomy: six key points of operative skill for
      achieving better urinary continence].
AB  - Postoperative urinary incontinence is a major impairment to patients' quality of
      life after prostatectomy, and is not limited to laparoscopic total prostatectomy.
      Improvements in devices and techniques of laparoscopic surgery have facilitated
      reliable cancer control, and in this situation there will now be increasing focus
      on postoperative quality of life (QOL), particularly urinary incontinence.
      Between July 2007 and March 2009, we have performed laparoscopic total
      prostatectomy for 53 patients, focusing on techniques to reduce urinary
      incontinence. Here we report the details of six key points of operative skill for
      achieving better urinary continence. These include (1) minimal distal incision of
      the endopelvic fascia; (2) preservation of the bladder neck; (3) bilateral nerve
      sparing surgery; (4) preservation of the puboprostatic ligament and its
      refixation to the anterior aspect of the bladder neck (bladder neck sling
      suspension); (5) preservation of the posterior (membranous) urethra; (6) suturing
      of the posterior aspect of the rhabdosphincter, the remaining portion of the
      Denonvilliers fascia, and the bladder neck (restoration of the Denonvilliers
      fascia). Moreover, we separated the 53 patients into two groups: those who were
      not treated using the above six key points, and those who were. We then compared
      the data for the two groups with regard to the time taken for continence
      recovery, operative parameters (operation time and bleeding), and postoperative
      pathological findings.

PMID- 20158073
TI  - [Investigation of adverse events and the continuance rate of silodosin in all
      patients who received silodosin for lower urinary tract symptoms suggestive of
      benign prostatic hyperplasia].
AB  - OBJECTIVES: We retrospectively evaluated patients who received silodosin for
      lower urinary tract symptoms suggestive of benign prostatic hyperplasia
      (BPH/LUTS) in our hospital, to investigate its efficacy, adverse events and
      continuance rate. METHODS: From the release of silodosin (July 2006) through
      October 2008, 256 patients received silodosin for BPH/LUTS in our hospital. Of
      these 256, we evaluated 195, as 61 were excluded due to conditions such as
      prostate cancer. We evaluated the International Prostate Symptom Score (IPSS),
      quality of life (QOL) index, uroflowmetry and postvoid residual urine volume
      before and after medication. We calculated the continuance rate of the drug by
      the Kaplan-Meier method. RESULTS: The patients' mean age was 68.1 years and the
      mean medicated period was 3.1 months. Overall severity at baseline estimated by
      the criteria for severity of BPH was mild in 0%, moderate in 69%, and severe in
      31%. Silodosin significantly improved the IPSS, QOL index, maximum urinary flow
      rate and postvoid residual urine volume in 90 patients whose data were available
      for analysis of the efficacy. Improvements were observed both in voiding symptoms
      and in storage symptoms. However, 45.6% of the overall efficacy was insufficient.
      Adverse events were observed in 56 of the 195 cases (28.7%). The most common
      adverse event was abnormal ejaculation (10.8%). The patients who reported adverse
      events were significantly younger in age and had lower IPSS and QOL index values
      after treatment than those without adverse events (mean age: 65.4 vs. 69.2 years
      old; mean IPSS: 7.7 vs. 13.1, mean QOL index: 2.9 vs. 3.6). The continuance rate
      for the drug was 12.0% at 1 year on the Kaplan-Meier curve. The development of
      adverse events was involved in the low continuance rate of silodosin.
      CONCLUSIONS: Modification of treatment such as dose reduction is necessary to
      continue silodosin.

PMID- 20158074
TI  - [Usefulness of screening for prostate cancer with prostate specific antigen (PSA)
      in the medical checkup ("human dock") at Onomichi Municipal Hospital: clinical
      significance of the cases diagnosed as prostate cancer].
AB  - PURPOSE: The usefulness of the screening for prostate cancer with prostate
      specific antigen (PSA) in the medical checkup ("Human Dock") at Onomichi
      Municipal Hospital was evaluated. METHODS: From April 1997 to December 2007,
      serum PSA of 1,234 male (median age: 59) was measured in the medical checkup and
      each parameter of screening was evaluated. In addition, for the cases with
      prostate cancer, results of treatment and clinical significance were assessed.
      RESULTS: PSA was elevated in 82 cases (6.6%), aged 42-87 (median 64), in which
      PSA varied 3.1-66.5 ng/ml (median 5.4). Trans-rectal biopsy was performed in 35
      cases and prostate cancer was detected in 15 (42.9% of biopsied cases and 1.2% of
      whole group), aged 58-81 (median 70), with PSA value 4.2-66.5 ng/ml (median
      10.3). Clinical stage of these cases was cT1cN0M0 in 12 and cT2aN0M0 or more in
      3, Gleason score was 3 + 3 in 4 and 3 + 4 or more in 11. Initial treatment was
      radical prostatectomy in 12, androgen-deprivation therapy in 2 and external beam
      irradiation in 1. During the follow-up for 8-107 months (median 60), 14 were
      alive with good control and 1 was alive with relapse. Only one case was
      "clinically insignificant" cancer (impalpable and localized and tumor volume less
      than 0.5 ml and Gleason score 3 + 3 or less). CONCLUSIONS: Most of the prostate
      cancers detected in the medical checkup were clinically significant, therefore,
      PSA screening doesn't result in overtreatment and it is meaningful to perform PSA
      screening in the medical checkup.

PMID- 20158075
TI  - [Significance of serum creatinine measurement in the specific screening test
      system for detection of chronic kidney disease].
AB  - OBJECTIVE: A specific screening test system for detection of Metabolic Syndrome
      was started in April 2008. This test includes urine protein but omits serum
      creatinine. This test system assumes this position based on the view that health
      guidance or recommendation of health examination in subjects diagnosed with
      hypertension or diabetes mellitus will help detect otherwise overlooked renal
      dysfunction. I conducted an investigation to obtain evidence that the specific
      screening test system can detect CKD. MATERIALS AND METHODS: The investigation
      was conducted in 931 subjects who had been examined for urine protein, blood
      pressure, blood glucose, and serum creatinine. This investigation was invested
      with an aim to determine the frequency of renal dysfunction among the subjects in
      whom CKD is ruled out in the specific screening test because they test negative
      for urine protein. RESULTS: Of the 931 subjects, 169 developed a positive test
      for urine protein. Of 762 subjects testing negative for urine protein, 226 had
      renal dysfunction with eGFR <60 ml/min/1.73 m2. The urine protein test alone let
      57.2% (226/395) of subjects escape the detection of CKD. Of the 226 subjects, 156
      had hypertension and/or diabetes mellitus and were found to have renal
      dysfunction when their serum creatinine concentration was determined. As a
      result, the rate of CKD overlooking was reduced to 17.7% (70/395), but the
      sensitivity and specificity of this test system were 69.0% and 43.7%,
      respectively. It is still insufficient in these respects. CONCLUSION: The
      specific screening test system let 226 of 395 subjects (57.2%) escape the
      detection of CKD. This result suggests that the test system should include the
      measurement of serum creatinine concentration.

PMID- 20158076
TI  - [Two cases of infants with acute renal failure due to bilateral obstructive
      ureteral stones associated with rotavirus gastroenteritis].
AB  - We report on 2 infants with acute renal failure caused by bilateral obstructive
      ureteral stones associated with rotavirus gastroenteritis. A 28-month boy and a
      13-month boy with several days history of watery diarrhea and vomiting were
      referred to our hospital because of anuria. They were diagnosed acute post-renal
      failure due to obstructive bilateral ureteral stones based on the findings of
      ultrasound scan and computed tomography. Immediately, percutaneous nephrostomy
      tubes were inserted for urinary drainage, serum levels of creatinine and uric
      acid returned to normal within several days. Sandy stones were excreted through
      the nephrostomy tubes with urine after urinary alkalization, which were proved to
      be mainly ammonium acid urate. Ammonium acid urate is rare in developed
      countries, but some cases of bilateral urolithiasis causing acute renal failure
      in infants with rotavirus gastroenteritis were reported in recent years. It has
      been known that the cause of acute renal failure is renal azotemia resulting from
      sustained hypovolemia, but post-renal causes due to ammonium acid urate stones
      should be taken into consideration.

PMID- 20158077
TI  - [Limbic encephalitis in the course of testicular lymphoma].
AB  - The malignant tumor patient tends to develop various neuropathy by direct
      invasion, metastasis, secondary infectious disease of tumor, metabolic disorders,
      vascular damage and adverse drug reactions with a treatment, and, however, it
      rarely appear by mechanism of autoimmunization. Tumor tissue with paraneoplastic
      neurological syndrome (PNS) produces an antigen attacking nerve tissue by it's
      cross reaction, and many studies indicates that there are a few kinds of
      antineuritic antibodies occurred by the charactor of malignant diseases or the
      patterns of progression. There is no relationship between the symptoms and the
      progression of disease. We report a case of malignant testicular tumor presented
      the paraneoplastic limbic encephalitis which is one of paraneoplastic
      neurological syndrome.

PMID- 20158078
TI  - [Prevention of wound complications after salvage total laryngectomy following
      chemoradiotherapy with a pectoralis major muscle interposition flap].
AB  - There is an increased risk of wound complications in patients undergoing salvage
      laryngectomy following chemoradiotherapy. To reduce the rate of wound
      complications after a salvage total laryngectomy, a fresh tissue reinforcement of
      the pharyngeal suture line (pharyngeal interposition graft) has been reported to
      be useful. In the present study, wound complications after a salvage total
      laryngectomy with a pectoralis major muscle flap as a pharyngeal interposition
      graft were analyzed. Four patients with recurrent laryngeal cancer (three with
      supraglottic, and one with glottic cancer) after chemoradiotherapy underwent
      salvage total laryngectomy using a pectoralis major muscle interposition flap.
      Minor wound complications were observed in three of the four patients, with an
      infection around the tracheostoma, a minor subcutaneous abscess, and a
      superficial skin necrosis in one patient each. These complications were managed
      with local wound care. No patients had major wound complications such as
      pharyngocutaneous fistulas. There were no necroses or wound complications of the
      pectoralis major muscle flap. This study has suggested that the pectoralis major
      muscle flap as a pharyngeal interposition graft is safe and useful for prevention
      of wound complications in salvage total laryngectomy following chemoradiotherapy.

PMID- 20158079
TI  - [MRI-CT fusion image navigation during surgery for inverted papilloma].
AB  - We report two cases of intraoperative computer-aided surgery using magnetic
      resonance imaging (MRI)/computed tomography (CT) fusion imaging for inverted
      papilloma (IP). Case 1: IP had spread to the frontal recess/sinus so we chose a
      combined endoscopic sinus surgery (ESS) and external approach. Case 2: For a
      maxillary sinus tumor, we combined ESS and the adjuvant external (Caldwell-Luc)
      procedure. This is helpful to surgeons when, shifting fusion imaging when opening
      the frontal sinus bone to obtain CT data, and shifting to MRI to detect the tumor
      pedicle, then approaching the bone defect using MRI-CT fusion imaging (50-50%).

PMID- 20158080
TI  - [A case report: multiple air embolism after the laryngopharyngoesophagectomy
      occurred by the cervical infection from postoperative fistula].
AB  - Systemic air embolism, a very rare clinical condition, has many causes. We report
      a case of multiple air embolisms following laryngopharyngoesophagectomy salvage
      surgery for hypopharyngeal residual cancer after concurrent chemoradiotherapy.
      Cervical infection arose from a fistula caused by postoperative suture failure in
      which the 56-year-old man suddenly lost consciousness and went into shock. A few
      days post operation, an air embolism happened and caused in the brain, pulmonary,
      myocardiac and cerebral infarction. The man died two months after initial
      occurrence. We suspect that air entered through the ruptured left internal
      jugular vein via infection due to aspiration at the injury site. Air embolisms
      are associated with different medical maneuvers, and it is necessary to recognize
      that they may become a serious perioperative complication.

PMID- 20158081
TI  - [Structural insights of PPARgamma].

PMID- 20158082
TI  - [Recent advances in PPARgamma research].
AB  - PPARgamma is a member of the nuclear receptor superfamily and a molecular target
      of the thiazolidinedione class of antidiabetic drugs. PPARgamma was initially
      characterized as a central regulator of adipocyte differentiation. Recent
      advances in PPARgamma research have revealed diverse pathophysiological actions
      of PPARgamma such as regulation of expression of adipokines and inflammatory
      mediators, adipose tissue macrophage polarization, atherosclerosis formation and
      bone development. Here, we highlight recent advances in our current understanding
      the biological actions of PPARgamma.

PMID- 20158083
TI  - [PPARgamma target genes and the molecular mechanism of transcriptional control by
      PPARgamma].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonist such as
      thiazolidinedione (TZD) has important roles in inflammation and cancer in
      addition to the control of energy conservation, adipocyte differentiation and
      insulin sensitivity. PPARgamma is a ligand-activated nuclear receptor. In the
      absence of ligand, the transcriptional activity of PPARgamma is suppressed
      through the association with N-CoR/SMRT and histone deacetylases. Upon binding of
      ligand to PPARgamma, PPARgamma binds several coactivators and regulates the
      expression of its target genes in various tissues. To understand various effects
      of TZD, we summarize the transcriptional control by PPARgamma focused on
      coactivators and target genes regulated by PPARgamma.

PMID- 20158084
TI  - [PPARG gene polymorphism and disease susceptibility].
AB  - PPARgamma plays a key role in the regulation of adipocyte differentiation and
      energy balance. The polymorphism in human PPARG gene resulting in the
      substitution of Pro12 to Ala in the PPARgamma2 isoform has been established as
      conferring anti-diabetic and anti-obesity effects, especially in the conditions
      such as westernized lifestyle with high levels of endogenous ligands for
      PPARgamma. Thus this is a good example of gene-environment interaction in human
      diseases. Since this polymorphism is predicted to generate a less active
      transcription factor, several different phases for metabolism in vivo with regard
      to PPARgamma activities are assumed.

PMID- 20158085
TI  - [Critical roles of PPARgamma in every aspect of the metabolic syndrome].
AB  - Obesity, defined by an excess fat storage in adipose tissues, is an integral
      component of the metabolic syndrome. Excess fat in adipose tissues is often
      accompanied by ectopic lipid deposition in non-adipose tissues such as liver,
      skeletal muscle and pancreas. The deleterious systemic effects of lipid
      accumulation in adipose and non-adipose (lipotoxicity) tissues have prompted us
      to propose the term, "adipotoxicity" to highlight the whole body impacts of
      adipocyte dysfunction on the pathophysiology of the metabolic syndrome. PPARgamma
      is a master regulator of adipocyte differentiation and function and thereby
      serves as a key target in delineating and combating the syndrome. Here, we
      overview the pathophysiological role of PPARgamma from the standpoint of
      adipocyte dysfunction with special reference to fatty liver disease and
      hypertension.

PMID- 20158086
TI  - [Regulation of differentiation and hypertrophy of adipocytes and adipokine
      network by PPARgamma].
AB  - PPARgamma is a ligand-activated transcription factor that serves as a central
      regulator of adipocyte differentiation. PPARgamma has been the focus of intense
      research since its discovery as a molecular target of the thiazolidinedione class
      of drug. Here we review regulation of differentiation and hypertrophy of
      adipocytes and adipokine network by PPARgamma with an emphasis on their
      influences on systemic glucose and lipid metabolism. Specific topics include the
      mechanism by which both activation of PPARgamma by thiazolidinedione and
      haploinsufficiency of PPARgamma leads to insulin sensitivity and recent advance
      in our understanding of the role of adiponectin and adipose tissue macrophages in
      insulin sensitizing action of thiazolidinedione.

PMID- 20158087
TI  - [Anti-atherosclerotic effects by PPARgamma and its ligands through the activation
      of reverse cholesterol transport system].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a nuclear
      receptor superfamily which agonists were in clinical use for anti-diabetic
      therapy. Recent studies both in vivo and in vitro revealed that PPARgamma
      agonists have anti-atherosclerotic effects which is also demonstrated by a large
      clinical trial including PROactive study. One of the mechanisms for this effect
      is the activation of reverse cholesterol transport through the induction of ABCA1
      transporter by PPARgamma agonists. The transporter exports cholesterol from
      macrophages migrating in the vasculature and inhibits the formation of foam cell
      which contains lipid droplet in the cytosol as cholesterol ester. Clinical
      application of PPARgamma agonists have beneficial effects by preventing the
      cardiovascular events in diabetic patients.

PMID- 20158088
TI  - [Mechanism of sex differences and the clinical significance of PPARgamma targeted
      drugs].
AB  - Peroxisome proliferator-activated receptor (PPAR) gamma is the nuclear receptor
      which mainly distributes in adipose tissues. It plays a key role in the
      differentiation of adipocytes. In Japan, pioglitazone hydrochloride (Actos) is
      the only drug which targets PPARgamma among antidiabetic drugs. It had been
      reported that there are sex differences in pharmacological and side effects of
      pioglitazone hydrochloride. This is a brief overview on the mechanism of sex
      differences of this drug, especially focusing on the role of sex hormones on
      PPARgamma expression. Moreover, we also considered about the effects of such
      differences on clinical applications from our research of prescribing data in 20
      hospitals and also the result of PRospective ACTos practICAL experience
      (PRACTICAL).

PMID- 20158089
TI  - [Roles of PPARgamma in preventing the development of atherosclerosis in LDL
      receptor null mice].
AB  - Thiazolidinediones are synthetic ligands for peroxisome proliferator activated
      receptor gamma. They have been demonstrated to possess cardioprotective effects
      in humans and antiatherogenic properties in animal models. We observed that
      atherosclerosis in low-density lipoprotein receptor null mice progressed when
      mice were fed a high-fat diet. Pioglitazone treatment of atherogenic mice
      prevented this progression of atherosclerosis from its middle stages of disease.
      However, pioglitazone, in combination with the withdrawal of a high-fat diet, was
      unable to reverse established atherosclerosis. These findings describe, in part,
      a general paradox of how therapeutic agents are evaluated in common murine models
      of atherosclerosis and the lack of therapeutic benefit of agents given to mice
      with established atherosclerotic lesions, and further, may have implications for
      human therapy.

PMID- 20158090
TI  - [Evidences demonstrating the effects of anti-atherosclerotic actions of
      pioglitazone--special emphasis on PROactive Study and PERISCOPE Study].
AB  - Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial
      infarction and stroke. There is indirect evidence that agonists of PPARgamma
      could reduce macrovascular complications. PROactive Study was conducted to
      ascertain whether pioglitazone reduces macrovascular morbidity and mortality in
      high-risk patients with type 2 diabetes. Subjects were 5,238 patients with type 2
      diabetes who had evidence of macrovascular disease. Subjects were assigned
      patients to oral pioglitazone titrated from 15 mg to 45 mg (n=2,605) or matching
      placebo (n=2,633), to be taken in addition to their glucose-lowering drugs and
      other medications. The primary endpoint was the composite of all-cause mortality,
      non-fatal myocardial infarction, stroke, acute coronary syndrome, endovascular or
      surgical intervention in the coronary or leg arteries, and amputation above the
      ankle. Analysis was by intention to treat. The average time of observation was
      34.5 months. 514 of 2,605 patients in the pioglitazone group and 572 of 2,633
      patients in the placebo group had at least one event in the primary composite
      endpoint (HR 0.90, 95% CI 0.80-1.02, p=0.095). The main secondary endpoint was
      the composite of all-cause mortality, nonfatal myocardial infarction, and stroke.
      301 patients in the pioglitazone group and 358 in the placebo group reached this
      endpoint (0.84, 0.72-0.98, p=0.027). Thus, pioglitazone reduced the composite of
      all-cause mortality, non-fatal myocardial infarction, and stroke in patients with
      type 2 diabetes who have a high risk of macrovascular events. PERISCOPE Study,
      double-blind, randomized, multicenter trial in 543 patients with coronary disease
      and type 2 diabetes, was conducted to find out the reasons why pioglitazone
      demonstrated the anti-atherosclerotic action. A total of 543 patients underwent
      coronary intravascular ultrasonography and were randomized to receive
      glimepiride, 1 to 4 mg, or pioglitazone, 15 to 45 mg, for 18 months with
      titration to maximum dosage, if tolerated. Atherosclerosis progression was
      measured by repeat intravascular ultrasonography examination. As far as the
      change in percent atheroma volume (PAV) from baseline to study completion is
      concerned, mean PAV increased 0.73% (95% CI, 0.33-1.12%) with glimepiride and
      decreased 0.16% (95% CI, -0.57-0.25%) with pioglitazone (p=0.002). Thus, in
      patients with type 2 diabetes and coronary artery disease, treatment with
      pioglitazone resulted in a significantly lower rate of progression of coronary
      atherosclerosis compared with glimepiride.

PMID- 20158091
TI  - [PPARgamma targeted genome-based drug discovery; present and future direction].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to regulate
      growth arrest and terminal differentiation of adipocytes initially, and
      glitazones are used as a new class of antidiabetic drugs clinically. Recent
      understanding of the functions of PPARs, using genome-wide analysis, as
      pleiotropic regulators of biological responses, including not only lipid,
      lipoprotein, glucose homeostasis, but also inflammation, differentiation and
      proliferation of various cancer cells, and memory, have provided an opportunity
      to develop novel PPARs ligands with characteristic subtype selectivity. Such
      ligands are not only chemical tools to investigate the functions of PPARs, but
      also candidates for the treatment of PPARs-mediated diseases. This article
      summarizes recent topics of the medicinal chemistry work on the design, synthesis
      and pharmacological evaluation of PPARs related agents.

PMID- 20158092
TI  - [Recent trends in PPARgamma agonist development of thiazolidinediones and non
      thiazolidinediones].
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand
      activated transcription factor regulating gene expression involved in the fatty
      acids, lipoprotein and carbohydrate metabolism and inflammation. Its wide range
      of potential therapeutic actions make it attractive targets for the development
      of drugs treating metabolic disorders such as metabolic syndrome, type 2 diabetes
      and dyslipidemia. The thiazolidinediones (TZDs) insulin-sensitizer of PPARgamma
      agonist have been clinically used for insulin resistant and diabetes patients in
      a decade. Despite the proven benefits of TZDs, safety concerns have led to drop
      out of the various newly developed PPARgamma targeting drugs. Here, I summarize
      the therapeutic potential and adverse events of TZDs and non-TZDs class of
      PPARgamma modulators, and will discuss the future strategy of the PPARgamma
      modulator development.

PMID- 20158093
TI  - [Anti-vascular failure effects].
AB  - PPARgamma, which is a family of ligand-activated nuclear transcriptional factors,
      is expressed abundantly in macrophages and adipocytes and plays an important role
      in differentiation of these cells. PPARgamma gene is also expressed in vascular
      endothelial cells and vascular smooth muscle cells and PPARgamma has been shown
      to mediate anti-inflammation, anti-proliferation, pro-apoptotic, and anti
      migration activities. Further, there is accumulating evidence that PPARgamma is
      implicated as an important regulator of immune responses in various diseases
      including atherosclerosis. Pioglitazone, a PPARgamma ligand, has been recognized
      as antidiabetic agents for non-insulin-dependent diabetes mellitus and effective
      and safety profile of pioglitazone has been established in PROactive study.
      Recently, the mechanisms of PPARgamma-mediated vascular protective function have
      been elucidated by using the endothelial cell-specific knockout mice of the
      PPARgamma gene.

PMID- 20158094
TI  - [Regulation of allergic immune response of PPARgamma agonists--emerging roles in
      allergic response].
AB  - PPARgamma is expressed in a variety of immunocompetent cells and has
      immunoregulatory activities. In line with the in vitro observations that
      PPARgamma agonists down-regulate inflammatory cytokines production and cellular
      responses, PPARgamma agonists have protective effects in a variety of mouse model
      of inflammatory disorders. In this review, we summarize the functional roles of
      PPARgamma in immunocompetent cells from the perspective of the pathophysiology of
      allergic diseases. The anti-allergic effects of PPARgamma agonist in vitro and in
      vivo indicate the possibility that PPARgamma agonists could be new therapeutic
      modality for allergic disease.

PMID- 20158095
TI  - [Anti-cancer action by PPARgamma ligand].
AB  - Accumulating evidences have shown that thiazolidinediones (TZDs), PPARgamma
      ligands, could exert anti-cancer actions in several human cancer cells. TZDs are
      capable to inducing growth inhibition, apoptosis and inhibition of cell invasion,
      thereby leading to their anti-cancer effects. The growth inhibition was mediated
      by a cyclin-dependent kinase inhibitor, p27(Kip1), accumulation which is induced
      by both inhibition of ubiquitylation of p27(Kip1) and reduction of degradation
      activity of p27(Kip1) by proteasome. In addition, a recent clinical observation
      has showed a 33% reduction in lung cancer risk among TZD users who have diabetes
      mellitus compared with nonusers, strongly suggesting TZDs possess clinically
      relevant actions. These results suggest that TZDs may be novel agents to treat
      malignant tumor.

PMID- 20158096
TI  - [Pleiotropic effects of PPARgamma agonists on bone remodeling].
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates both
      glucose and bone mass. PPARgamma activation has been shown to affect bone through
      an increased in bone marrow adiposity and decreased in osteoblastogenesis,
      resulting in reduced bone formation. In fact, clinical studies have reported that
      PPARgamma agonists may cause increased risk of bone fractures and decreased bone
      mineral density. On the other hand, PPARgamma agonists may have protective effect
      on inflammatory bone resorption through inhibition of RANKL- or TNFalpha-induced
      osteoclastogenesis. In this report, we review recent studies showing pleiotropic
      effects of PPARgamma agonists on bone formation and inflammatory bone resorption
      observed at joints in rheumatoid arthritis.

PMID- 20158097
TI  - [Anti-inflammatory effect of PPARgamma agonists: basics and clinical
      applications].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) plays critical roles
      on insulin sensitivity and adipocyte differentiation, and therefore, several
      agonists such as pioglitazone and rosiglitazone are used as anti-diabetic drugs.
      In addition to the original use, clinical applications for the therapy of several
      specific inflammatory diseases such as inflammatory bowel disease and rheumatoid
      arthritis are expected, because many reports indicated the anti-inflammatory
      effects of PPARgamma agonists on various animal disease models. In fact, several
      drugs and compounds are used or under clinical trials for the therapy of
      rheumatoid arthritis, ulcerative colitis, and other inflammation-related
      diseases. Further clinical applications for the therapy of intractable or chronic
      inflammatory diseases will be progressed.

PMID- 20158098
TI  - [A target of PPARgamma agonist: diabetes mellitus].
AB  - The members of the PPARgamma agonists, such as the thiazolidinediones, act as
      insulin sensitizer and improve insulin resistance. Several clinical studies have
      evaluated the efficacy of PPARgamma agonists in the management of insulin
      resistance and type 2 diabetes mellitus (T2DM). They are believed to improve
      insulin resistance by stimulating differentiation of small adipocytes,
      normalizing serum adipocytokine profile, and protecting pancreatic beta cells.
      They also possess powerful anti-atherogenic potency through amelioration of lipid
      profile and their anti-inflammatory effects. The PROactive study demonstrated
      that pioglitazone protects against hard end-point of macrovascular events in T2DM
      patients with previous macrovascular disease. A number of studies have also
      proven the potency of PPARgamma agonists in the prevention of onset of T2DM.

PMID- 20158099
TI  - [Effects of PPARgamma agonist on dyslipidemia and atherosclerosis].
AB  - Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor and
      ligand-activated transcription factor which plays important roles in the control
      of energy balance. The thiazolidinediones (TZDs), in use as an insulin
      sensitizing agent, are well known as the PPARgamma agonist. Recent studies
      reported that PPARgamma agonists involve in lipid metabolism through regulating
      genes including lipoprotein lipase, CD36, and ABCA1. Some clinical trials have
      been shown that TZD decreased serum levels of LDL-cholesterol and triglycerides
      and increased serum levels of HDL-cholesterol in type 2 diabetes. In addition,
      activation of PPARgamma is implicated in the regulation of endothelial function,
      proliferation and migration of vascular smooth muscle cells, and activation of
      macrophages.

PMID- 20158100
TI  - [Metabolic syndrome].
AB  - The metabolic syndrome means the state of glucose intolerance caused by insulin
      resistance, and develops lipid abnormality and high blood pressure. Recently,
      life style is changed to excessive energy intake by a high fat diet and physical
      activity according to the spread of automobiles decline in. Then, the appearance
      of disease of obesity and the metabolic syndrome increases. In this text, a basic
      pathogenesis of the metabolic syndrome and the clinical application of PPARgamma
      agonist to the metabolic syndrome are outlined.

PMID- 20158101
TI  - [Protective role of PPARgamma agonists against cardiovascular disease].
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear
      receptor protein. It functions as a master transcriptional factor that promotes
      differentiation of preadipocytes by activating adipose-specific gene expression.
      Recently, PPARgamma activity has been shown to influence the gene expression
      involved in carbohydrate and lipid metabolism. Indeed, pioglitazone and
      rosiglitazone, ligands for PPARgamma, improve insulin resistance in diabetic
      patients, and now become one of the most popular anti-diabetic drugs in the
      developed countries. Moreover, there is accumulating data that PPARgamma ligands
      exert anti-inflammatory, anti-oxidative and anti-proliferative effects on
      vascular wall cells. These observations suggest that PPARgamma agonist may have
      atheroprotective properties as well through its pleiotropic effects. In this
      paper, we review the clinical utility of PPARgamma agonist in the treatment of
      cardiovascular disease.

PMID- 20158102
TI  - [PPARgamma agonists for the diseases of gastrointestinal tract and liver].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the
      nuclear receptor superfamily, is expressed in colonic epithelial cells at high
      levels and is assumed to play an important physiological role in the gut. In
      vitro as well as animal model experiments showed considerable anti-cancer and
      anti-inflammatory effects of thiazolidinedione (TZD) PPARgamma agonists in the
      colon. Therefore, in the gastroenterology field, much attention has been focused
      on the efficacy of TZD on the treatment of colorectal cancer and inflammatory
      bowel diseases (IBD). Although we only have very limited clinical evidence at
      present, TZD might be useful for the chemoprevention of colorectal cancer and
      treatment of mild to moderately active inflammatory bowel diseases, which warrant
      further clinical studies.

PMID- 20158103
TI  - [The role of PPARgamma agonists in kidney diseases].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      dependent transcription factor that has a central role in the regulation of
      insulin sensitivity and adipocyte differentiation. Expression of PPARgamma has
      been reported in the kidney, including medullary collecting ducts, glomeruli and
      tubular cells. Thiazolidinediones (TZDs) are synthetic PPARgamma agonists and are
      used widely in patients with type 2 diabetes. It has been gradually discovered
      that TZDs have various other actions, such as vascular protective, anti
      inflammatory, anti-fibrotic and anti-proliferative actions, over and above their
      effects on glucose and lipid metabolism. In this review, we will focus on current
      knowledge and insights on the role of PPARgamma agonists in kidney diseases,
      especially in diabetic nephropathy, non-diabetic kidney diseases and dialysis
      therapy.

PMID- 20158104
TI  - [PPARgamma and cancer].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to regulate
      cell growth and differentiation of adipocytes and a variety of tissues, and has
      been demonstrated to be up regulated in many cancer tissues, including colon and
      breast cancers. I here summarize the role of PPARgamma signaling evoked by
      PPARgamma agonists and antagonists in cancer development, and discuss the
      potential application of PPARgamma ligands for cancer chemoprevention. A growth
      suppressive effect of PPARgamma agonist is well exemplified in a chemically
      induced colon cancer model in mice. It is interesting to note that inhibition of
      PPARgamma signaling also shows suppressive effects on cell invasion and
      metastasis in both in vitro and in vivo settings. A more detailed analysis is
      warranted to dissect the molecular basis for the tumor suppressive function of
      PPARgamma.

PMID- 20158105
TI  - [Alzheimer's disease].
AB  - The insulin resistance and peripheral hyperinsulinemia have been known to promote
      the neurodegeneration in Alzheimer's disease (AD), such as beta amyloid (Abeta)
      deposits and increase of tau hyperphosphorylation. Therefore, correcting insulin
      dysregulation may offer a novel strategy for the treatment of AD. Pharmacologic
      treatment with thiazolidinedions, such as rosiglitazone and pioglitazone,
      agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma
      (PPARgamma), may offer some therapeutic relief of AD by lowering peripheral
      insulin and enhancing insulin sensitivity. In addition, PPARgamma agonists have
      been shown to inhibit inflammatory gene expression, alter Abeta homeostasis and
      exhibit neuroprotective effects. PPARgamma agonists represent a new and
      potentially efficacious treatment of AD.

PMID- 20158106
TI  - [PPARgamma agonists as potential therapeutic drugs for allergic diseases].
AB  - The nuclear receptor PPARgamma exerts a potent anti-inflammatory effects on
      immune cells and connective tissue cells. Accumulating evidences indicate that
      pathophysiological contribution of PPARgamma in allergic disease including
      asthma. Most recently, clinical efficacy and tolerability of PPARgamma agonists
      for asthma or atopic dermatitis have been reported. PPARgamma agonists seem to be
      new therapeutic drugs for allergic diseases, although further studies are
      required. Here we discuss the outlook for clinical significance of PPARgamma
      agonists for allergic diseases.

PMID- 20158107
TI  - [PPARgamma as a new therapeutic target in inflammatory diseases].
AB  - The peroxisome proliferator activated receptor-gamma (PPARgamma) is a nuclear
      receptor highly expressed in the gastrointestinal tract and playing a key role in
      inflammation. Several natural and synthetic PPARgamma ligands have been the focus
      of extensive research effort as potent anti-inflammatory agents in
      gastrointestinal diseases. In the last decade, accumulative experimental evidence
      has further suggested that PPARgamma is involved in several inflammatory
      signaling pathways associated with acute and chronic inflammation. The aims of
      this review are to discuss the potential roles of PPARgamma in the
      pathophysiology of the gastrointestinal tract, as well as the emerging
      therapeutic strategies targeting this receptor.

PMID- 20158108
TI  - [PPARgamma antagonist as a potential drug for the treatment of obesity and
      diabetes].
AB  - PPARgamma is a molecular target of thiazolidinedione class of antidiabetic drugs.
      Although activation of PPARgamma by thiazolidinedione improves insulin resistance
      in obese subjects, PPARgamma heterozygous knockout mice were resistant to a high
      fat diet induced obesity and insulin resistance, suggesting that a moderate
      reduction of PPARgamma activity could be beneficial for the treatment of obesity
      and insulin resistance. This hypothesis was supported by genetic evidences
      consistently showing that the common Pro12Ala variant of PPARgamma2, which causes
      a moderate reduction in transcriptional activity and adipogenic potential, has
      been associated with reduced weight gain and improved insulin sensitivity. We
      here review PPARgamma antagonism as a potential remedy for obesity and diabetes.

PMID- 20158109
TI  - [PPARgamma-gene therapy].
AB  - In recent years, there has been increasing evidence that peroxisome proliferators
      activated receptor gamma (PPARgamma) plays crucial roles in various
      pathophysiological processes, some of which are associated with a decrease in the
      expression of PPARgamma. Our previous study demonstrated that gene delivery of
      PPARgamma could be used to restore and/or enhance endogenous anti-inflammatory
      processes that are normally operative in mammalian tissues such as colon. In this
      review, we describe the outline of recent progress in the development of
      PPARgamma-gene therapy and PPARgamma molecular pathways, along with the results
      obtained in our previous experiments and those reported by others.

PMID- 20158110
TI  - [Birt-Hogg-Dube syndrome].
AB  - Birt-Hogg-Dube (BHD) syndrome is a rare disorder inherited in an autosomal
      dominant manner. The affected patients are predisposed to the development of
      cutaneous fibrofolliculomas, renal cell tumors and lung cysts with recurrent
      pneumothorax. The responsible gene for this syndrome is named BHD gene which is
      mapped in the region of chromosome 17p11.2. Based on the neoplastic changes in
      the skin and the kidney, BHD gene is regarded as a tumor-suppressor gene.
      However, detailed mechanism of tumorigenesis is not well understood. In this
      review, we summarize current understanding of BHD syndrome with special attention
      to the pathophysiology of lung cysts formation. Recent findings of the roles of
      BHD gene and its-encoding protein folliculin (FLCN) using rodent models are also
      discussed.

PMID- 20158111
TI  - [Thyroid and parathyroid surgery in Japan: comparison with western countries].

PMID- 20158113
TI  - [Effects of clinical pathways on postoperative diet].
AB  - Japanese medicine is now increasingly based on clinical pathways. The merits of
      reliance on a clinical pathway include the standardization of medicine which can
      thus shorten hospital stays, the induction of EBM (evidence-based medicine), and
      a reduction in unnecessary drugs or examinations. It is important to adopt new
      clinical pathways to maintain high-quality medical care. The establishment of
      such pathways will also help to rationalize and maximize the benefit of all
      medical treatments. A clinical pathway has been used more often in surgery than
      in the field of internal medicine. The new management method during the pre- and
      postoperative periods, such as the cessation of preoperative hair removal,
      administering a brief course of antimicrobial agents, and beginning food
      consumption in an earlier postoperative period, has been standardized with the
      establishment of clinical pathways. Postoperative infectious complications, such
      as surgical site infections, catheter-related infections, and methicillin
      resistant Staphylococcus aureus enteritis, have thus been reduced.

PMID- 20158114
TI  - [Recent changes in perioperative nutritional support in patients undergoing
      thoracoscopic esophagectomy].
AB  - The advent of thoracoscopic esophagectomy (TSE) has enabled early patient
      recovery in association with changes in perioperative nutritional support. This
      article reviews recent changes in the perioperative nutritional support for
      patients undergoing TSE. TSE associated with a laparoscopic procedure facilitates
      the recovery of gastrointestinal motility and function while decreasing the
      incidence of vocal cord paralysis and/or difficulties in swallowing due to
      accurate mediastinal lymph node dissection. Thus, recent trends in perioperative
      nutritional support have been early oral feeding and perioperative enteral
      feeding using a disease-specific polymeric immunoenhancing or immunomodulating
      enteral formula. Although TSE is associated with less surgical invasiveness,
      nutritional support still plays an important role in perioperative care to
      prevent postoperative complications and contribute to the early recovery of
      nutritional status. Moreover, since TSE is now performed to treat advanced
      esophageal cancer, patients are frequently malnourished preoperatively and
      therefore in the group at high risk for postoperative complications. The early
      start of oral feeding after the evaluation of swallowing function, selecting the
      appropriate route for enteral nutrition, and sufficient calorie intake during the
      perioperative period are essential to prevent postoperative pulmonary and/or
      infectious complications and consequently to improve patient quality of life.

PMID- 20158115
TI  - [A new concept of the postoperative oral feeding regimen after upper
      gastrointestinal surgery in the laparoscopic era].
AB  - "Nil by mouth" after abdominal surgery has well been accepted by gastrointestinal
      surgeons for many years. The tradition was that when patients passed flatus, they
      were ready to consume a liquid diet, and then a solid food diet was gradually
      introduced. This approach was taken to avoid aspiration, gastric and intestinal
      distension, and anastomotic dehiscence. Although studies demonstrated that the
      conventional strict feeding regimens were not necessary, many surgeons,
      especially upper gastrointestinal surgeons, still hesitated to allow early oral
      feeding. However, after the introduction of laparoscopic surgery, early feeding
      became more common as it was claimed that laparoscopic surgery reduced the
      occurrence of postoperative ileus and made the early initiation of an oral diet
      possible. Influenced by this, many surgeons now permit early oral feeding after
      open surgery with equal success. At present, an early postoperative oral diet has
      become more the standard of care in those undergoing major gynecologic and
      colorectal surgery. Although it is supported by few randomized clinical trials,
      it is assumed that early or immediate oral feeding is equally safe or even
      superior after upper gastrointestinal procedures such as hepatectomy and
      gastrectomy. Patient-controlled feeding in which patients consume food according
      to their preference even in the early postoperative period is another concept
      that appears promising.

PMID- 20158116
TI  - [Current practices of perioperative nutritional therapy in colorectal surgery].
AB  - Earlier oral intake after colorectal surgery can be achieved effectively with
      laparoscopic procedures. "Fast track" or "enhanced recovery after surgery"
      programs have attempted to reduce the physiologic stress of surgery.
      Perioperative care in such programs includes drinking a carbohydrate-rich
      beverage 2 hours before surgery and oral liquid intake on the day of surgery.
      Early restoration of gastrointestinal function can reduce postoperative
      complications and the length of hospital stays.

PMID- 20158117
TI  - [Nutritional support after hepatic surgery].
AB  - The liver is very important in maintaining the metabolism of the body and plays a
      pivotal role in integrating several biochemical pathways for carbohydrates, fat,
      protein, and vitamins. It is crucial to determine the nutritional status of the
      patient and provide adequate nutritional support during all phases of hepatic
      surgery. Progressive deterioration of nutritional status has been associated with
      a poor outcome of hepatic surgery. Postoperatively, patients should receive an
      early normal diet or enteral nutrition regardless of the type of hepatic surgery.
      Patients who receive early enteral nutrition have fewer postoperative infections
      and better nitrogen retention. Postoperative enteral nutrition yields superior
      results to the infusion of fluid and electrolytes alone. An energy intake of 35
      40 kcal/kg body weight/day and a protein intake of 1.2-1.5 g/kg body weight/day
      are recommended. In the long term, the introduction of a late evening snack can
      contribute to the maintenance of appropriate nutrition and prevent several
      metabolic complications such as obesity even with the occurrence of fatty liver.

PMID- 20158118
TI  - [Nutritional management in pancreatoduodenectomy patients].
AB  - Pancreatoduodenectomy is one of the most invasive and complex procedures in
      gastrointestinal surgery. Perioperative nutritional management, particularly
      enteral nutrition, is essential for patients undergoing pancreatoduodenectomy to
      attenuate postoperative complications and avoid progression of malnutrition due
      to surgical stress. Early enteral nutrition including immunonutrition via
      catheter jejunostomy is recommended from the viewpoint of protection from
      postoperative complications. If inadequate caloric administration via enteral
      nutrition alone cannot be achieved, combined enteral and parenteral nutrition is
      warranted. Postoperatively, feeding can potentially be started in the very early
      phase, similar to oral intake after gastrectomy. If adequate caloric
      administration cannot be achieved via enteral nutrition alone, combined enteral
      and parenteral nutrition is also warranted in the postoperative period. A fat
      restricted diet is preferable if pancreatic exocrine function is disturbed due to
      accompanying or chronic pancreatitis and the deterioration of the remnant
      pancreatic preserve. Aggressive administration of commercially available
      pancreatic exocrine enzymes is recommended to prevent malabsorption of dietary
      lipids in the subacute and chronic stages after pancreatoduodenectomy. Oral
      supplementation of n-3 polyunsaturated fatty acids can be used in postoperative
      pancreatic cancer patients.

PMID- 20158120
TI  - [Recent advances and future prospects in research of small bowel
      transplantation].

PMID- 20158121
TI  - [What we can learn from a case of medical malpractice--a case of suicide caused
      by bullying between male nurses].

PMID- 20158122
TI  - [Necrosectomy for acute necrotizing pancreatitis (infected pancreatic necrosis)].

PMID- 20158123
TI  - [What should we do to improve working environment for women surgeons?].

PMID- 20158124
TI  - [Approach to establishment of new health care team with introducing NP/PA (mid
      level clinician) system into Japan--lessons from nurse practitioner and physician
      assistant in Emory University, USA].

PMID- 20158125
TI  - [The role of physician assistant (PA) in cardiaothoracic surgery at Emory
      University Hospital].

PMID- 20158126
TI  - [Team medicine approach to the practice of anesthesiology--the role of anesthesia
      assistants].

PMID- 20158127
TI  - [The introduction of physician assistants and team working in British health
      care].

PMID- 20158128
TI  - [Skill mix in the UK].

PMID- 20158130
TI  - The impact of health literacy on self-monitoring of blood glucose in patients
      with diabetes receiving care in an inner-city hospital.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG) is considered to be 1 of the
      cornerstones of diabetes self-management. It is unclear whether inadequate health
      literacy affects SMBG. OBJECTIVE: The objective of this study was to examine the
      relationship between health literacy and SMBG. METHODS: This was a cross
      sectional survey of 189 patients with diabetes, aged 18 to 65 years, receiving
      care in a large urban, public health care setting. We measured health literacy
      using the shortened version of the Test of Functional Health Literacy in Adults.
      The diabetes care profile was used to determine the use of self-monitoring of
      blood glucose. RESULTS: Most (60.9%) of the survey participants were assessed as
      functionally health literate. The majority (90.9%) of the study participants
      reported testing their blood sugar at least once daily. Although adequate health
      literacy was associated with recording of blood sugar testing (p = .049), we
      found no statistically significant relationship between health literacy and the
      frequency of SMBG. Persons self-reporting having diabetes for more than 10 years
      were less likely to self-monitor blood glucose (odds ratio, 0.33; 95% CI, 0.11
      0.99). CONCLUSIONS: SMBG frequency is not independently associated with health
      literacy, but SMBG result recording is noted among patients with inadequate
      literacy.

PMID- 20158131
TI  - Optimizing hypertension management in underserved rural populations.
AB  - Rural populations across the United States have an increased likelihood of
      developing hypertension and diabetes, which are significant risk factors for
      cardiovascular disease (CVD), including stroke and myocardial infarction. Limited
      access to care due to geography or socioeconomic status significantly impairs
      control of hypertension in rural populations, resulting in poor health outcomes.
      Epidemiological studies suggest that the prevalence of uncontrolled hypertension
      and poor glycemic control are affected by race, increasing age, and residence in
      the rural southeastern United States. Optimization of the delivery of rural
      health care is needed to improve outcomes in patients with hypertension. New
      strategies such as programs targeting therapeutic inertia, home-based monitoring
      of blood pressure (BP), and Internet-based communication programs may
      significantly improve BP control rates among rural patients. Among hypertensive
      medications, angiotensin-converting enzyme inhibitors and angiotensin receptor
      blockers are recommended by consensus guidelines and may be particularly
      effective in rural, minority populations due to their secondary effects on
      decreasing CVD.

PMID- 20158133
TI  - Cardiovascular fitness and risk factors of healthy African Americans and
      Caucasians.
AB  - BACKGROUND: African Americans have a higher prevalence of and mortality rates
      from cardiovascular disease than Caucasians. One important risk factor for
      cardiovascular disease is poor cardiovascular fitness. We quantified associations
      between fitness and related primary risk factors for cardiovascular disease in
      healthy African Americans and Caucasians. METHODS AND RESULTS: Participants
      included African American (n = 91) and Caucasian (n = 51) men and women aged 18
      to 45 years with a body mass index less than 38 kg/m2, fasting blood glucose less
      than 126 mg/dL, and blood pressure less than 140/90 mm Hg. Fitness, waist and hip
      circumference, percent body fat, fasting blood glucose, insulin, lipid profiles,
      and C-reactive protein (CRP) were measured. The majority of African Americans
      (57.1%) were low-fair fitness (Caucasians, 31.4%), and only 20.8% were good/high
      fitness (Caucasians, 39.2%). The number of cardiovascular disease risk factors
      increased with decreasing fitness, and CRP was negatively associated with fitness
      in both groups. CONCLUSIONS: Low fitness may characterize apparently healthy
      African Americans as at risk for cardiovascular disease. Including fitness as a
      risk factor may improve early identification of at-risk African Americans.
      Importantly, prescribing exercise as medicine and promoting regular physical
      activity to improve fitness is essential among African Americans.

PMID- 20158132
TI  - Patient-reported outcomes: descriptors of nociceptive and neuropathic pain and
      barriers to effective pain management in adult outpatients with sickle cell
      disease.
AB  - Despite frequent episodes of severe recurrent pain in sickle cell disease (SCD),
      sensory pain in outpatient adults with SCD lacks sufficient characterization.
      Furthermore, pivotal barriers may interfere with these patients' adherence to
      prescribed analgesic therapies but have not been studied systematically. We
      describe sensory pain characteristics, barriers, and analgesic use reported by
      adults with SCD during routine clinic visits. Patients (N = 145; 67% female, 94%
      African American) completed measures on a pen-tablet computer. Patients reported
      an average of 3.6 +/- 2.3 pain sites; mean current pain intensity (3.3 +/- 3.2),
      least (3.0 +/- 2.7) and worst (4.9 +/- 3.5) pain intensity in 24 hours on a 0 to
      10 scale, multiple neuropathic (4.5 +/- 3.4, 8.3% selected none) and nociceptive
      (6.8 +/- 4.0) pain descriptors, and continuous pain pattern (59%). Their mean
      pain barriers score was 2.2 +/- 0.9, and 33% were dissatisfied with their pain
      levels. Only 14% reported taking at least 1 adjuvant drug, 82% were taking
      nonopioids, 85% step 2 opioids, and 65% step 3 opioids. Patients reported using,
      on average, 4.9 +/- 2.7 analgesics. Their pain barriers scores were similar to or
      greater than people with cancer. Importantly, their pain may be both nociceptive
      and neuropathic, contrary to common expectations that SCD pain is only
      nociceptive. Few patients, however, took drugs effective for neuropathic pain.

PMID- 20158134
TI  - UNOS-coordinated organ sales: toward improving the health and welfare of the
      historically underprivileged.

PMID- 20158135
TI  - Kidney donation: when all else fails, try a regulated market.

PMID- 20158136
TI  - Ethical concerns about an organ market.

PMID- 20158137
TI  - Primary care physicians' attitudes and practices regarding discussing organ
      donation with their patients.
AB  - PURPOSE: Among the general population, discussing organ donation with a primary
      care provider may be associated with increased willingness to donate. However,
      the frequency with which primary care providers hold these discussions with their
      patients has not been reported. SETTING: Cross-sectional mail and an Internet
      survey of validated questions regarding organ donation were done. SUBJECTS: A
      national sample of 831 primary care physicians. black, and Hispanic physicians
      were oversampled. RESULTS: Few physicians reported receiving formal training in
      donation (17%). Only 5% of physicians have donor cards available in their
      practice, and only 11% have donation information available in their practice.
      While 30% of physicians reported discussing end-of-life care with their patients,
      fewer than 4% reported discussing donation with their patients. However, only 36%
      felt that discussing donation was outside of their scope of practice. In a
      multivariate regression model, predictors of discussing donation with patients
      included having received formal education about organ donation (odds ratio [OR],
      2.6; p < .05) and discussing end-of-life care with patients (OR, 12.8; p < .001).
      CONCLUSIONS: Very few primary care physicians reported discussing organ donation
      with their patients despite the majority agreeing that it was within their scope
      of practice. Primary care physicians who had received education on the subject or
      who regularly discuss end-of-life care with their patients were more likely to
      discuss donation. Efforts to improve donation in the general population should
      include a focus on understanding and improving communication about organ donation
      between providers and their patients.

PMID- 20158138
TI  - Primary care physicians' attitudes and practices regarding discussing organ
      donation with their patients.

PMID- 20158139
TI  - A Texas response to the Sullivan Commission: the undergraduate medical academy
      model.

PMID- 20158140
TI  - A brief introduction to evaluating the literature.

PMID- 20158141
TI  - Health care reform on the brink.

PMID- 20158142
TI  - Characterization of calcium oxalate biominerals in Pereskia species (Cactaceae).
AB  - Calcium oxalate druses were isolated from the stems and leaves of six
      Pereskioideae family members and investigated by infrared spectroscopy, showing
      that in all samples the biomineral was present in the form of whewellite, CaC2O4
      x H2O. As Pereskia is thought to represent the "ancestral" condition of the
      leafless stem-succulent cacti, these results suggest that the biomineralization
      of calcium oxalate in Cactaceae represents a primitive characteristic of the
      group and also support a close genetic relationship between Pereskia and Opuntia.

PMID- 20158143
TI  - Anti-hepatitis B virus activity of new substituted pyrimidine acyclic nucleoside
      analogues.
AB  - A number of N-substituted pyrimidine acyclic nucleosides were synthesized by
      coupling reaction of 2-(2-chloroethoxy)ethyl acetate or (2,2-dimethyl-1,3
      dioxolan-4-yl)methyl 4-methylbenzenesulfonate with the corresponding base
      followed by deprotection. The synthesized compounds were tested for their
      antiviral activity against hepatitis B virus (HBV). The plaque reduction
      infectivity assay was used to determine virus count reduction as a result of
      treatment with the synthesized compounds which showed moderate to high antiviral
      activities.

PMID- 20158144
TI  - Anti-HIV activity of new substituted 1,3,4-oxadiazole derivatives and their
      acyclic nucleoside analogues.
AB  - A number of new 5-[(naphthalen-5-yloxy)methyl]-1,3,4-oxadiazole derivatives, 2-5
      and 8-11, were synthesized. The 2-{5-[(naphthalen-5-yloxy)methyl]-1,3,4-oxadiazol
      2-ylthio}acetohydrazones 6a and 6b were synthesized by the reaction of the
      hydrazide 4 with the corresponding monosaccharides. Cyclization of the sugar
      hydrazones 6a and 6b with acetic anhydride afforded the substituted oxadiazoline
      derivatives 7a and 7b. The synthesized compounds were evaluated for their
      antiviral activity against, the human immunodeficiency virus (HIV-1) and some of
      these compounds showed moderate to high antiviral activity.

PMID- 20158146
TI  - Antimicrobial activity of new 2,4-disubstituted thiazolidinone derivatives.
AB  - A number of new disubstituted 2,5-thiazolidinone derivatives were synthesized and
      tested for their antimicrobial activity against Bacillus subtilis (Gram
      positive), Pseudomonas aeruginosa (Gram-negative), and Streptomyces species
      (Actinomycetes). They displayed different degrees of antimicrobial activities or
      inhibitory actions.

PMID- 20158145
TI  - Antimycobacterial activity of natural and semi-synthetic lignans.
AB  - The antimycobacterial activity of (-)-cubebin (1), hinokinin (2), and some of
      their semisynthetic derivatives, namely (-)-O-acetyl-cubebin (3), (-)-O-methyl
      cubebin (4), (-)-O-(N,N-dimethylamine-ethyl)-cubebin (5) and (-)-6,6'
      dinitrohinokinin (6), was evaluated against Mycobacterium tuberculosis (ATCC
      27294), M. kansasii (ATCC 12478), and M. avium (ATCC 15769). The MIC values
      ranged from 31.25 to 2000 microg/mL. Among the evaluated compounds, 2 displayed a
      MIC value of 62.5 microg/mL against M. tuberculosis, while 3 and 4 displayed MIC
      values of 62.5 and 31.25 microg/mL, respectively, against M. avium. All compounds
      were inactive against M. kansasii. These are promising results concerning the
      search for biologically active natural products, highlighting that new approaches
      to the prevention, treatment, and cure of tuberculosis are extremely important.

PMID- 20158147
TI  - Activity of armillarisin B in vitro against plant pathogenic fungi.
AB  - The methanolic extract of the fruiting bodies of the mushroom Armillariella
      tabescens was found to show antifungal activity against Gibberella zeae. The
      active compound was isolated from the fruiting bodies of A. tabescens by bioassay
      guided fractionation of the extract and identified as armillarisin B.
      Armillarisin B eventually corresponds to 2-hydroxy-2-phenylpropanediamide and its
      structure was confirmed on the basis of spectroscopic studies including 2D NMR
      experiments.

PMID- 20158148
TI  - Schistosomicidal evaluation of Zanthoxylum naranjillo and its isolated compounds
      against Schistosoma mansoni adult worms.
AB  - Chemical investigation of the EtOAc fraction (EF) obtained from the ethanolic
      extract of Zanthoxylum naranjillo (Rutaceae) leaves (EE) by preparative HPLC
      resulted in the isolation of protocatechuic acid (1), gallic acid (2), p
      hydroxybenzoic acid (3), and 5-O-caffeoylshikimic acid (4). This is the first
      time that the presence of compounds 1-4 in Z. naranjillo has been reported.
      Compounds 1-4, the EE, and EF were tested in vitro against Schistosoma mansoni
      adult worms. The results showed that the S. mansoni daily egg production
      decreased by 29.8%, 13.5%, 28.4%, 17.7%, 16.3%, and 6.4%, respectively. Compounds
      1 and 3 were also able to separate adult worm pairs into male and female. This
      activity may be correlated with the reduction in egg production, since 1 and 3
      showed better inhibitory properties compared with 2 and 4.

PMID- 20158149
TI  - Evaluation of antinociceptive and anti-inflammatory activities of a new
      triterpene saponin from Bauhinia variegata leaves.
AB  - A new triterpene saponin, named as 23-hydroxy-3alpha-[O-alpha-L-1C4
      rhamnopyranosyl-(1"-->4')-O-alpha-L-4C1-arabinopyranosyl-oxy]olean-12-en-28-oic
      acid O-alpha-L-1C4-rhamnopyranosyl-(1""'-->4"")-O-beta-D-4C1-glucopyranosyl-(1""-
      >6"')-O-beta-D-4C1-glucopyranosyl ester (9), was isolated from the leaves of
      Bauhinia variegata Linn. In addition, six flavonoid compounds along with two
      cinnamic acid derivatives were isolated and identified based on their
      chromatographic properties, and chemical and spectral data (ESI-high resolution
      MSn, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, and HMBC). Compound 9 was found to be
      nontoxic (LD50) and to have significant anti-inflammatory and antinociceptive
      activities. It also showed a slight antischistosomal activity.

PMID- 20158150
TI  - Menthalactone, a new analgesic from Mentha cordifolia Opiz. Leaves.
AB  - * Author for correspondence and reprint requests Z. Naturforsch. 64c, 809-812
      (2009); received May 7/July 23, 2009 Menthalactone, a new long-chain alkene with
      a bicyclic lactone moiety, was isolated as an analgesic constituent from the
      leaves of Mentha cordifolia Opiz. At a dosage of 100 mg/ kg mouse, it decreased
      the number of squirms induced by acetic acid by 67.3%. Statistical analysis using
      Kruskall Wallis one-way analysis of variance by ranks showed that menthalac-tone
      is different from the solvent control at alpha = 0.01 and approximates the
      analgesic activity of mefenamic acid at 0.001 level of significance.

PMID- 20158151
TI  - Antiviral activity of Solanum paniculatum extract and constituents.
AB  - Solanum species are traditionally employed as antiherpes and anticancer agents in
      different countries. S. paniculatum has widespread ethnomedical uses in Brazil,
      including the treatment of viral infections. This paper reports on the isolation
      of neotigogenin (1) and the new compound delta25(27)-tigogenin-3-O-beta-D
      glucopyranoside (2), obtained as a mixture of R and S diastereoisomers at C22
      from an ethanol extract of S. paniculatum leaves, along with the determination of
      their cytotoxicity against Vero cells and antiviral effect against human herpes
      virus type 1 (HHV-1), murine encephalomyocarditis virus (EMCv), and vaccinia
      virus strain Western Reserve (VACV-WR). The extract of S. paniculatum inhibited
      HHV-1 replication [EC50 = (298.0 +/- 11.2) microg/ml] and showed no effect on
      EMCv and VACV-WR. On its turn, 1 was inactive against the assayed strains but
      presented high cytotoxicity [CC50 = (2.03 +/- 0.03) microg/ml], whereas 2
      exhibited significant antiherpes [EC50 = (170.8 +/- 1.7) microg/ml] and
      antivaccinia virus effects [EC50 = (177.0 +/- 3.3) microg/ml], with low
      cytotoxicity (CC50 > 400 microg/ml). The results corroborate Solanum paniculatum
      as a source of cytotoxic and antiviral compounds.

PMID- 20158152
TI  - Chemical and biological investigation of Araucaria heterophylla Salisb. resin.
AB  - Three labdane diterpenes, namely lambda-8(17),14-diene, 13-epicupressic acid, and
      13-Oacetyl-13-epicupressic acid, were isolated from the resin collected from stem
      exudates of Araucaria heterophylla Salisb. (Araucariaceae). The isolated
      compounds were identified using different spectroscopic methods (1H NMR, 13C NMR,
      HMQC, HMBC and COSY). The resin extract showed antiulcerogenic activity against
      ethanol-induced stomach ulcers in Sprauge Dawely rats using ranitidine as
      standard. In addition, the resin and the isolated compounds showed variable
      cytotoxic activities against breast (MCF7) and colon (HCT116) cancer cell lines.

PMID- 20158153
TI  - Bioactive metabolites produced by Penicillium sp. 1 and sp. 2, two endophytes
      associated with Alibertia macrophylla (Rubiaceae).
AB  - In the course of our continuous search for bioactive metabolites from endophytic
      fungi living in plants from the Brazilian flora, leaves of Alibertia macrophylla
      (Rubiaceae) were submitted to isolation of endophytes, and two species of
      Penicillium were isolated. The acetonitrile fraction obtained in corn from a
      culture of Penicillium sp. 1 afforded orcinol (1). On the other hand, Penicillium
      sp. 1 cultivated in potato-dextrose-broth furnished two different compounds,
      cyclo-(L-Pro-L-Val) (2) and uracil (3). The chromatographic fractionation of the
      acetonitrile fraction obtained from Penicillium sp. 2 led to three
      dihydroisocoumarins, 4-hydroxymellein (4), 8-methoxymellein (5) and 5
      hydroxymellein (6). Compounds 5 and 6 were obtained from the Penicillium genus
      for the first time. Additionally, metabolites 1-6 were evaluated for their
      antifungal and acetylcholinesterase (AChE) inhibitory activities. The most active
      compounds 1 and 4 exhibited detection limits of 5.00 and 10.0 microg against
      Cladosporium cladosporioides and C. sphaerospermum, respectively. Compound 2
      showed a detection limit of 10.0 microg, displaying potent AChE inhibitory
      activity.

PMID- 20158154
TI  - Inhibition of the initiation stage of carcinogenesis by Salvia disermas
      constituents.
AB  - Phytochemical studies of an ethanolic extract of the aerial parts of Salvia
      disermas resulted in the isolation of seven known compounds, rosmarinic (1) and
      caffeic (2) acids, salvigenin (3), luteolin (4), luteolin 7-O-beta-arabinoside
      (5), luteolin 7-O-beta-glucoside (6), and ocotillol II (7). The initiation stage
      of carcinogenesis is triggered by activation of procarcinogens by phase I
      enzymes, such as cytochrome P-450 1A, and oxidative stress that leads to DNA
      damage. The initiation stage is countered by phase II detoxification enzymes such
      as glutathione S-transferases (GST), quinine reductase (QR), epoxide hydrolase
      (mEH) besides conjugation with thiols. We aimed to investigate the cancer
      chemopreventive and tumour anti-initiating activity of the ethanolic extract of
      the aerial parts of Salvia disermas and its constituents. The S. disermas extract
      was a promising inhibitor of CYP1A activity, inducer of GST, QR, and mEH
      activities, enhancer of thiol content, radical scavenger, and inhibitor of DNA
      damage. On the other hand, 3 was an enhancer of thiol content and QR activity,
      while 4 was an inhibitor of CYP1A activity, inducer of QR activity, and radical
      scavenger of ROO*, and 5 was an inducer of GST activity and inhibitor of DNA
      damage. The present study indicated that the ethanolic extract of S. disermas and
      4 are promising anti-initiating and multipotent blocking agents.

PMID- 20158155
TI  - Structure-activity relationships of aromadendranes in uterus-relaxant activity.
AB  - Aromadendranes belong to a class of sesquiterpenes present in higher plant
      essential oils and marine animals. Although the biological activities include
      antifungal, antibacterial, antiviral, plant growth regulatory, antifeedant,
      repellent and cytotoxic, there is only one precedent for spasmolytic effects. In
      a previous report we have shown that the aromadendrene molecule known as
      spathulenol, isolated from Lepechinia caulescens, efficiently relaxes rat uterus
      rings and therefore in the present work we describe structure-activity
      relationships of thirteen aromadendranes, most of them having the trans-fused
      perhydroazulene skeleton, with spasmolytic activity.

PMID- 20158156
TI  - Variation in chemotactic preferences of Aphanomyces cochlioides zoospores to
      flavonoids.
AB  - The zoospores of the phytopathogenic Aphanomyces cochlioides are chemotactically
      attracted by a host-specific flavone, cochliophilin A (5-hydroxy-6,7
      methylenedioxyflavone), and repelled from the mammalian estrogens or estrogenic
      compounds. This study further examined the responses of A. cochlioides zoospores
      to some flavonoids structurally related to cochliophilin A or compounds known as
      phytoestrogens. The bioassay revealed that some synthetic flavones (such as 6
      methyl-4'-methoxyflavone, 3-hydroxy-4'-methoxyflavone, 7-hydroxy-5-methylflavone,
      3-hydroxy-4'-methoxy-6-methylflavone) elicited attractant activity at
      concentrations as low as picomolar (10 pM), which was an 100-fold lower
      concentration than that of the threshold concentration of the host-specific
      attractant cochliophilin A. Apparently, a hydrophobic B-ring with an alkylated
      (methylated) A-ring or a methoxylated B-ring with an unsubstituted A-ring in the
      flavone skeleton played a significant role in higher attractant activity. On the
      other hand, all known estrogenic flavonoids (such as equol, 3'- or 8-prenylated
      naringenins) displayed potent repellent activity toward zoospores. Surprisingly,
      zoospores were attracted by non-estrogenic 6-prenylated naringenin indicating
      that repellent activity is linked to the estrogenic activity of the
      phytoestrogens.

PMID- 20158157
TI  - Effects of oxygen supply on growth and carotenoids accumulation by
      Xanthophyllomyces dendrorhous.
AB  - The effects of oxygen supply on growth and carotenoids accumulation by
      Xanthophyllomyces dendrorhous were studied. Initial volumetric oxygen transfer
      coefficients (K(L)a) within the range 21.5-148.5 h(-1) had significant effects on
      growth and carotenoids accumulation, and an increase of the initial K(L)a value
      led to higher carotenoids, astaxanthin and biomass yields by X. dendrorhous. At
      an initial K(L)a value of 148.5 h(-1), a maximal cell concentration of 19.37 g 1(
      1) and optimal carotenoids and astaxanthin productions of 18.1 and 14.5 mg 1(-1)
      were obtained, as well as a maximal astaxanthin content of 0.8 mg g DCW(-1),
      respectively. A higher oxygen supply was advantageous to astaxanthin biosynthesis
      and the ratio of astaxanthin in the total carotenoids. An increasing initial
      K(L)a value gave stronger fluorescence intensities by X. dendrorhous, resulting
      in the maximal intensity of fluorescence at the K(L)a value 148.5 h(-1). The cell
      growth of X. dendrorhous was significantly inhibited when dissolved oxygen
      tension (DOT) was controlled at approximately 20% air saturation, which was due
      to the oxygen limitation in broth. The astaxanthin yield and content at
      approximately 50% DOT were higher than those at approximately 20% DOT.

PMID- 20158158
TI  - Growth and antioxidant responses in Jatropha curcas cotyledons under lead stress.
AB  - Jatropha curcas embryos were grown in vitro to observe the effects of lead on
      cotyledon responses. The cotyledon biomass increased initially and then decreased
      with increasing lead concentration. The SOD activity increased gradually up to
      200 microM and then decreased. The POD activity showed a similar trend. The CAT
      activity was increased at all lead concentrations, the highest activity being
      observed at 200 microM. However, the PAL activity was inhibited significantly
      except for 100 microM. Anaylsis by electrophoresis suggested a significant
      correlation between lead concentration and patterns of SOD, POD and CAT
      isoenzymes, and these results were consistent with changes of the antioxidant
      enzyme activities as assayed in solution.

PMID- 20158159
TI  - Agrobacterium rhizogenes-mediated transformation of Hypericum tomentosum L and
      Hypericum tetrapterum Fries.
AB  - This is the first evidence on successful Agrobacterium rhizogenes-mediated
      genetic transformation of two species from the genus Hypericum, H. tomentosum L.
      and H. tetrapterum Fries. Hairy root cultures were induced from root segments of
      both Hypericum species by two agropine wild-type strains of A. rhizogenes, ATCC
      15834 and A4. The transgenic character of the hairy root cultures was proved by
      PCR amplification of the rolABCD genes. In some H. tetrapterum transgenic lines
      aux genes were detected as well.

PMID- 20158160
TI  - Induction of pyridine alkaloid formation in transformed root cultures of
      Nicotiana tabacum.
AB  - Hairy root cultures of Nicotiana tabacum were set up by excised root tips with
      Agrobacterium rhizogenes. The successful transformation was confirmed by
      analyzing rolC and virC genes using polymerase chain reaction (PCR). Hairy root
      cultures were employed to study the formation of pyridine alkaloids, mainly
      nicotine. The transformed cultures were incubated with potential elicitors, such
      as methyljasmonate, quercetin and salicylic acid, in order to stimulate the
      biosynthesis of pyridine alkaloids. Profile and amounts of pyridine alkaloids
      were analyzed using capillary GLC-MS. Treatment of the cultures with
      methyljasmonate (50 microM) increased the alkaloid accumulation ca. 7-fold up to
      a level of 0.58 mg/g fresh weight as compared to untreated controls. Quercetin
      (200 microM) enhanced the alkaloid production ca. 4-fold (0.34 mg/g fresh weight)
      within 24 h. In contrast salicylic acid in all tested concentrations decreased
      the alkaloid level to 1 microg/g fresh weight. Also the inhibitory effect of
      salicylic acid on the elicitation effect of methyljasmonate and quercetin was
      investigated.

PMID- 20158161
TI  - Cloning and expression of Brassica napus beta-carbonic anhydrase cDNA.
AB  - A new full-length beta-carbonic anhydrase cDNA was obtained from Brassica napus
      by homologous cloning. The cDNA has an open-reading frame of 996 nucleotides,
      encoding 331 amino acids with a calculated molecular weight of 35,692 Da and an
      estimated pI value of 5.459. The deduced amino acid sequence of beta-carbonic
      anhydrase from Brassica napus shared significant identity with beta-carbonic
      anhydrases from Brassica carinata, Arabidopsis thaliana, and Thlaspi caerulescens
      (97.9%, 94%, and 93.5% identity, respectively). This cDNA was expressed in
      Escherichia coli BL21 (DE3) using the expression vector pET-32a(+). The
      expression band corresponded to the calculated mass plus the N-terminal fusion
      protein derived from the vector.

PMID- 20158162
TI  - Addition of restriction fragment length polymorphism markers to the genetic
      linkage map of Brassica rapa L. (syn. campestris).
AB  - Genetic linkage analysis of 151 restriction fragment length polymorphism (RFLP)
      loci, that included eight new loci, detected by the six probes in the present
      study, and four trait loci including seed colour, leaf pubescence, resistance to
      white rust caused by Albugo candida race-2 (AC-2) and race-7 (AC-7) employing the
      MAPMAKER/EXP 3.0 programme led to the development of 10 linkage groups (LGs)
      spanning over 44.4 centiMorgan (cM) to 130.4 cM containing 9 to 22 loci and two
      short LGs with two or three marker loci in Brassica rapa. The enriched map covers
      993.1 cM of B. rapa genome with an average marker interval of 6.41. Eight new
      RFLP loci occupied new map positions on five linkage groups, LG 2, 3, 6, 8 and 9.
      Addition of these RFLP loci led to appreciable changes in the corresponding
      linkage groups and resulted in an increase of the total map length by 102.8 cM
      and of the marker interval by 0.35 cM. Interval mapping by using the computer
      programme MAPMAKER/ QTL 1.1 for scanning the genetic map led to the detection of
      one major quantitative trait locus (QTL) in LG 4 and one minor QTL in LG 8
      governing resistance to AC-7. Both QTLs contributed 7.89 to the interaction
      phenotype (IP) score with 96.3% genetic variation. The multi-locus model
      suggested additive gene action with 96.8% genetic variation.

PMID- 20158163
TI  - Molecular and phylogenetic analysis of pyridoxal phosphate-dependent
      acyltransferase of Exiguobacterium acetylicum.
AB  - The pyridoxal-5'-phosphate (PLP)-dependent family of enzymes is a very diverse
      group of proteins that metabolize small molecules like amino acids and sugars,
      and synthesize cofactors for other metabolic pathways through transamination,
      decarboxylation, racemization, and substitution reactions. In this study we
      employed degenerated primer-based PCR amplification, using genomic DNA isolated
      from the soil bacterium Exiguobacterium acetylicum strain SN as template. We
      revealed the presence of a PLP-dependent family of enzymes, such as PLP-dependent
      acyltransferase, and similarity to 8-amino-7-oxononoate synthase. Sequencing
      analysis and multiple alignment of the thymidine-adenine-cloned PCR amplicon
      revealed PLP-dependent family enzymes with specific confering codes and consensus
      amino acid residues specific to this group of functional proteins. Amino acid
      residues common to the majority of PLP-dependent enzymes were also revealed by
      the Lasergene MegAlign software. A phylogenetic tree was constructed. Its
      analysis revealed a close relationship of E. acetylicum to other bacteria
      isolated from extreme environments suggesting similarities in anabolic
      adaptability and evolutionary development.

PMID- 20158164
TI  - Characterization and localization of the vacuolar-type ATPase in the midgut cells
      of silkworm (Bombyx mori).
AB  - The vacuolar ATPase (V-ATPase) is a multifunctional enzyme that consists of
      several subunits. Subunit B is a part of the catalytic domain of the enzyme. The
      result of the RT-PCR suggested that the V-ATPase B subunit is a ubiquitous gene.
      24 h after the larvae were infected with the Bombyx mori nucleopolyhedrovirus
      (BmNPV), the expression level of the V-ATPase B subunit in the midgut of the
      resistant strain NB was about 3 times higher than in the susceptible strain 306,
      and then the expression level of the V-ATPase B subunit decreased rapidly to a
      very low level. This indicated that the virus may cause a lot of changes of
      physiological conditions in the midgut. Localization of the V-ATPase B subunit
      was attempted in midgut cells of Bombyx mori by immunohistochemistry. The
      immunohistochemical localization with the antibody against the B subunit revealed
      a positive staining in goblet cell apical membranes of Bombyx mori midgut cells
      as well as in the midgut of Manduca sexta. This sequence has been registered in
      GenBank under the accession number EU727173.

PMID- 20158165
TI  - [Child welfare and child protection].

PMID- 20158166
TI  - [Child endangerment: a research update regarding etiology, consequences,
      diagnostics, and intervention].
AB  - In Germany child protection law is governed by the term "child endangerment".
      Based on a definition of that term recent research on child maltreatment is
      reviewed. Regarding etiology the need to go beyond risk factors and to consider
      risk mechanisms is highlighted. The discussion on the impact of child
      maltreatment focuses on the often underestimated effects of early neglect. After
      a review of progresses regarding the evaluation of maltreated children and the
      assessment of risk based on a systematic literature review suggestions for design
      of effective family interventions after abuse or neglect are made.

PMID- 20158167
TI  - [Child protection in Germany in light of the "MPK"-decisions--what's become of
      that?].
AB  - Child protection has become a political and social hot topic. Due to dramatic
      cases of child neglect and maltreatment federal and state governments as well as
      municipalities with their respective responsibilities are in public focus. The
      knowledge, that families and children, who must live under difficult conditions,
      need special attention, contact and support is the common aim of many activities.
      Under the impression of publicly discussed horrific violence against children and
      their death, the main federal and state decision-makers--the chancellor and the
      prime ministers of the states--have dealt with the protection of children. To be
      effective against neglect and maltreatment, in their conferences on 19th December
      2007 and 12th June 2008, they have decided a package of concrete measures for an
      active child protection. This paper gives an overview of these agreed measures
      and reports on the status of implementation.

PMID- 20158168
TI  - [Reflections on the legal foundations of working together to safeguard children].
AB  - The following essay outlines the legal foundations of child protection in
      Germany. It can be shown that constitutional law postulates a balance between
      parents responsibility on the one hand and public assignment to safeguard
      children on the other hand. The article focuses on the impact of legislative
      provisions on practitioners working together to safeguard children. Discussion of
      the demands of successful cooperation in the field of child protection shows that
      the political debate focuses somewhat to much on questions of control. It is
      argued that prospective development of child protection law should rather be
      based on a thorough debate of the demands in the respective professional domains.

PMID- 20158169
TI  - [Subjective parental stress as indicator for child abuse risk: the role of
      emotional regulation and attachment].
AB  - The Child Abuse Potential Inventory (CAPI) is an evidence-based procedure for the
      assessment of the risk for child abuse in parents. In this study, a German
      translation of the CAPI was applied to a normal sample of German parents (N =
      944). Descriptive analysis of the CAPI scores in the German provides findings
      comparable to the original standardization sample. The subjects' child abuse risk
      score was associated with demographic characteristics like education, marital
      status, occupation and gender. Long-term stability of the child abuse risk score
      and associations with individual differences in emotional regulation and
      attachment were investigated in a sub-sample of mothers with high and low child
      abuse risk scores (N = 69). The findings proved long-term stability. Furthermore
      associations between the child abuse risk score and anger dispositions were found
      which, however, were moderated by attachment differences. The findings suggest
      attachment security as a protective factor against child abuse.

PMID- 20158170
TI  - A new optical label-free biosensing platform based on a metal-insulator-metal
      structure.
AB  - A new label-free biosensing platform is proposed based on a metal-insulator-metal
      (MIM) structure. This platform allows us to perform biosensing by a simple
      reflectivity measurement at normal incidence illumination without using any bulky
      optical setup. Theoretical calculation was made to find optimized MIM structural
      parameters, and experimental results on the label-free biosensing using the MIM
      platform are presented. This platform has greater sensitivity and mass resolution
      with respect to the anomalous reflection method, which is a label-free biosensing
      platform previously proposed by us. Hence, it is suitable for high throughput
      analysis of biomolecular detection in a microarray format.

PMID- 20158171
TI  - Facile fabrication of homogeneous 3D silver nanostructures on gold-supported
      polyaniline membranes as promising SERS substrates.
AB  - We report a facile synthesis of large-area homogeneous three-dimensional (3D) Ag
      nanostructures on Au-supported polyaniline (PANI) membranes through a direct
      chemical reduction of metal ions by PANI. The citric acid absorbed on the Au
      nuclei that are prefabricated on PANI membranes directs Ag nanoaprticles (AgNPs)
      to self-assemble into 3D Ag nanosheet structures. The fabricated hybrid metal
      nanostructures display uniform surface-enhanced Raman scattering (SERS) responses
      throughout the whole surface area, with an average enhancement factor of 10(6)
      10(7). The nanocavities formed by the stereotypical stacking of these Ag
      nanosheets and the junctions and gaps between two neighboring AgNPs are believed
      to be responsible for the strong SERS response upon plasmon absorption. These
      homogeneous metal nanostructure decorated PANI membranes can be used as highly
      efficient SERS substrates for sensitive detection of chemical and biological
      analytes.

PMID- 20158172
TI  - Characterization of streptavidin binding to biotinylated, binary self-assembled
      thiol monolayers--influence of component ratio and solvent.
AB  - Many biosensor applications are based on streptavidin (SA) binding to partially
      biotinylated self-assembled thiol monolayers (SAMs). In our study, binary SAMs on
      gold were prepared from solutions containing 16-mercapto-1-hexadecanol (thiol I)
      and N-(8-biotinyl-3,6-dioxa-octanamidyl)-16-mercaptohexadecanamide (thiol II) in
      varying component ratios. Either chloroform or ethanol was used as solvent. After
      24 h thiol incubation, SA was immobilized on the resulting SAMs using the strong
      SA-biotin interaction. The SA binding process was monitored by QCM-D (quartz
      crystal microbalance monitoring dissipation factor). It is shown that the
      Sauerbrey equation is valid to calculate the mass quantities of the immobilized
      SA layers. Under the chosen incubation conditions, marginal fractions of the
      biotinylated component II in chloroform ((n(I)/n(II))(solution) approximately =
      1000) lead to SAMs which ensure a maximal SA binding quantity of m(Sauerbrey SA)
      approximately = 400 ng x cm(-2), being equivalent to a SA single-layer
      arrangement on the SAM surface. In case of incubations from ethanolic solutions,
      a complete SA layer formation needs significantly higher amounts of the
      biotinylated component II during SAM preparation ((n(I)/n(II))(solution)
      approximately = 50). X-ray photoelectron spectroscopy data show that the fraction
      of biotinylated thiol II in the SAM determines the amount of surface-bound SA.
      The SAM thiol ratio ((n(I)/n(II))(SAM)) not only depends on the corresponding
      component ratio in the incubation solution, but is also strongly influenced by
      the solvent. Using chloroform as solvent during SAM preparation significantly
      increased the fraction of biotinylated thiol II in the SAMs compared to ethanol.

PMID- 20158173
TI  - Fabrication of triacetylcellulose-SiO2 nanocomposites by surface modification of
      silica nanoparticles.
AB  - We have successfully fabricated triacetylcellulose (TAC) polymer-silica
      nanocomposite films having up to 40 wt % of incorporated silica nanoparticles by
      deliberately designing a surface ligand that has a structure similar to that of
      polymer repeating units and effectively modifying the surface of silica
      nanoparticles through chemical bonding. Cross-sectional TEM analysis reveals no
      significant aggregation in all TAC-silica nanocomposite films. Thermal analysis
      results suggested that TAC-silica nanocomposites had higher T(g) and T(c) values
      as compared to pure TAC, and the increase in T(g) and T(c) was affected by the
      silica content. The transparency of all the nanocomposite films was over 80% in
      the visible range, confirming the excellent compatibility of nanoparticles with
      TAC. In this study, we enhance the interaction between nanoparticles and polymer
      matrices by modifying the surface of nanoparticles with a ligand that has a
      structure similar to that of polymer repeating units. It is expected that this
      method can be applied to other polymer systems to develop useful nanocomposites.

PMID- 20158174
TI  - Piston-rotaxanes as molecular shock absorbers.
AB  - We describe the thermomechanical response of a new molecular system that behaves
      as a shock absorber. The system consists of a rodlike rotaxane connected to a
      piston and tethered to a surface. The response of this system is dominated by the
      translational entropy of the rotaxane rings and can be calculated exactly. The
      force laws are contrasted with those for a rigid rod and a polymer. In some
      cases, the rotaxanes undergo a sudden transition to a tilted state when
      compressed. These piston-rotaxanes provide a potential motif for the design of a
      new class of materials with a novel thermomechanical response.

PMID- 20158175
TI  - Consolidation of hydrophobic transition criteria by using an approximate energy
      minimization approach.
AB  - Recent experimental work has successfully revealed pressure induced transition
      from Cassie to Wenzel state on rough hydrophobic substrates. Formulas, based on
      geometric considerations and imposed pressure, have been developed as transition
      criteria. In the past, transition has also been considered as a process of
      overcoming the energy barrier between the Cassie and Wenzel states. A unified
      understanding of the various considerations of transition has not been apparent.
      To address this issue, in this work, we consolidate the transition criteria with
      a homogenized energy minimization approach. This approach decouples the problem
      of minimizing the energy to wet the rough substrate, from the energy of the
      macroscopic drop. It is seen that the transition from Cassie to Wenzel state, due
      to depinning of the liquid-air interface, emerges from the approximate energy
      minimization approach if the pressure-volume energy associated with the impaled
      liquid in the roughness is included. This transition can be viewed as a process
      in which the work done by the pressure force is greater than the barrier due to
      the surface energy associated with wetting the roughness. It is argued that
      another transition mechanism, due to a sagging liquid-air interface that touches
      the bottom of the roughness grooves, is not typically relevant if the substrate
      roughness is designed such that the Cassie state is at lower energy compared to
      the Wenzel state.

PMID- 20158176
TI  - Layer-by-layer deposited chitosan/silk fibroin thin films with anisotropic
      nanofiber alignment.
AB  - Chitosan/silk fibroin multilayer thin films were assembled using layer-by-layer
      deposition. The resultant multilayer films contained nanofibers aligned parallel
      to the dipping direction. Fiber deposition and orientation was enabled uniquely
      by a judicious choice of solvent and drying conditions and layer-by-layer
      assembly with chitosan. The deposition of oriented nanofibers was found to be the
      result of a unique combination of layer-by-layer and Langmuir-Blodgett type
      processing. Fiber orientation was confirmed by fast Fourier transform (FFT)
      analysis of optical micrographs and atomic force microscopy (AFM). Bidirectional
      fiber alignment was realized by rotating the substrate between multilayer
      deposition steps. Infrared spectroscopy revealed that the silk fibroin adopted
      the silk II secondary structure in the deposited films. We anticipate that these
      anisotropic films are able to combine the biocompatibility of a natural polymer
      system with the mechanical strength of SF, two properties useful in many
      biological applications including scaffolds suitable for guiding cell attachment
      and spreading.

PMID- 20158177
TI  - Intramolecular proton transfer in calixphyrin derivatives.
AB  - Calix[4]phyrins are convenient models for porphyrin metabolism intermediates.
      They also attract attention as complexation agents in macromolecular chemistry.
      For the biological function and chemical properties, their flexibility plays an
      important role. In this study, we explore the inner hydrogen motion previously
      detected in some calix[4]phyrins as a slow chemical exchange in the NMR spectra
      (J. Am. Chem. Soc. 2004, 126, 13714). The potential energy surface of this motion
      is defined by two generalized coordinates and modeled at DFT levels. The
      transitional barriers thus obtained agree reasonably well with those calculated
      from dynamic (1)H NMR measurements. The transitions over both the sp(2) and sp(3)
      links are found to be possible. During the transfer, an intermediate is formed
      where the two hydrogen atoms are attached to the neighboring nitrogens.
      Surprisingly, the barriers channeling the sp(2) and sp(3) paths in significantly
      depend on the dispersion and other interactions between remote side chains. The
      results confirm the possibility of a fine-tuning of the calixphyrin core
      properties by distant substituents.

PMID- 20158180
TI  - Multistimuli responsive organogels based on a new gelator featuring
      tetrathiafulvalene and azobenzene groups: reversible tuning of the gel-sol
      transition by redox reactions and light irradiation.
AB  - For the development of multistimuli responsive organogels, the new organic
      gelator LMWG 1, featuring electroactive TTF and photoresponsive azobenzene
      groups, was designed and studied. By manipulating the redox state of the TTF
      group in LMWG 1, the gel-sol transition for organogels with the LMWG 1 can be
      reversibly tuned by either chemical or electrochemical oxidation/reduction
      reactions. Alternatively, the photoisomerization of the azobenzene group in LMWG
      1 can also trigger the gel-sol transition. Therefore, organogels with LMWG 1
      respond not only to thermal stimuli but also to redox reactions and light
      irradiation.

PMID- 20158179
TI  - Measuring the energetics of membrane protein dimerization in mammalian membranes.
AB  - Thus far, quantitative studies of lateral protein interactions in membranes have
      been restricted peptides or simplified protein constructs in lipid vesicles or
      bacterial membranes. Here we show how free energies of membrane protein
      dimerization can be measured in mammalian plasma membrane-derived vesicles. The
      measurements, performed in single vesicles, utilize the quantitative imaging FRET
      (QI-FRET) method. The experiments are described in a step-by-step protocol. The
      protein characterized is the transmembrane domain of glycophorin A, the most
      extensively studied membrane protein, known to form homodimers in hydrophobic
      environments. The results suggest that molecular crowding in cellular membranes
      has a dramatic effect on the strength of membrane protein interactions.

PMID- 20158181
TI  - Synthesis and structural determination of multidentate 2,3-dithiol-stabilized Au
      clusters.
AB  - Interface bond structure, in addition to the well-known size and shape quantum
      confinement effects, is another factor that affects the properties of
      nanomaterials that is less known and studied. Inspired by the thiol-bridging
      "staple" motif (RS-Au-SR, Jadzinsky; et al. Science 2007, 318, 430.) discovered
      from monothiol-stabilized gold nanoclusters, dithiol ligand 2,3
      dimercaptopropanesulfonic (DMPS) acid has been employed to synthesize dithiol
      protected Au clusters (DTCs). The structure and property of the Au DTCs are
      studied to probe two effects: the entropy gain of dithiol over monothiol ligand
      protection and the constraint to the formation of the thiol bridging surface
      bonding. The hydrodynamic sizes of Au DTCs were estimated by diffusion nuclear
      magnetic resonance (NMR). The size distribution, Au core plus ligands on solid
      support, was confirmed by atomic force microscope (AFM) imaging. Size-dependent
      optical properties were observed. Au(4) clusters at high purity, characterized by
      mass spectrometry and organic-metal ratio confirmed by thermogravimetric analysis
      (TGA), display a characteristic absorbance band at 282 nm. The proton chemical
      environments as well as Au-S bond information of the Au(4) cluster were fully
      elucidated by (13)C-(1)H heteronuclear single-quantum coherence (HSQC) in
      conjunction with other two-dimensional (2D) NMR techniques. The Au-S bonding was
      further studied in thiol stretching by infrared and Au(4f) and S(2p) electrons by
      X-ray photoelectron spectroscopy (XPS). One possible structure of the Au(4)
      cluster has been proposed that needs further theoretical studies or single
      crystal confirmation.

PMID- 20158183
TI  - Direct determination of the insulin-insulin receptor interface using transferred
      cross-saturation experiments.
AB  - Insulin initiates metabolic control by binding to the insulin receptor (IR) on
      target cells. Kinetic and mutational analyses have revealed two binding sites on
      the insulin molecule and the residues that compose them. However, direct
      determination of the insulin-IR interface is required to distinguish those
      residues that contribute to receptor binding from those required for structural
      stability. Here, we successfully characterized one binding site using the nuclear
      magnetic resonance (NMR) transferred cross-saturation method, which can directly
      determine the binding interface of a large protein-protein complex. The results
      showed that this binding site contained three residues that have not been
      identified previously by mutational analyses. On the basis of the structure of
      the contact site, we also identified a molecule that can displace insulin from
      the IR. In addition, we discuss the mode of interaction between insulin and its
      receptor relative to the NMR analyses.

PMID- 20158182
TI  - Probing substituent effects in aryl-aryl interactions using stereoselective Diels
      Alder cycloadditions.
AB  - Stereoselective Diels-Alder cycloadditions that probe substituent effects in aryl
      aryl sandwich complexes were studied experimentally and theoretically.
      Computations on model systems demonstrate that the stereoselectivity in these
      reactions is mediated by differential pi-stacking interactions in competing
      transition states. This allows relative stacking free energies of substituted and
      unsubstituted sandwich complexes to be derived from measured product
      distributions. In contrast to gas-phase computations, dispersion effects do not
      appear to play a significant role in the substituent effects, in accord with
      previous experiments. The experimental pi-stacking free energies are shown to
      correlate well with Hammett sigma(m) constants (r = 0.96). These substituent
      constants primarily provide a measure of the inductive electron-donating and 
      withdrawing character of the substituents, not donation into or out of the
      benzene pi-system. The present experimental results are most readily explained
      using a recently proposed model of substituent effects in the benzene sandwich
      dimer in which the pi-system of the substituted benzene is relatively unimportant
      and substituent effects arise from direct through-space interactions.
      Specifically, these results are the first experiments to clearly show that OMe
      enhances these pi-stacking interactions, despite being a pi-electron donor. This
      is in conflict with popular models in which substituent effects in aryl-aryl
      interactions are modulated by polarization of the aryl pi-system.

PMID- 20158184
TI  - Synthesis, in vitro and in vivo biological evaluation, docking studies, and
      structure--activity relationship (SAR) discussion of dipeptidyl boronic acid
      proteasome inhibitors composed of beta-amino acids.
AB  - A series of novel dipeptidyl boronic acid proteasome inhibitors composed of beta
      amino acids were synthesized, in vitro and in vivo biologically evaluated, and
      theoretically modeled for the first time. From the screened racemic compounds in
      enzyme, 4i was the most active. The IC(50) value of its pure enantiomer 4q was
      9.6 nM, 36-fold more active than its isomer 4p and as active as the marketed
      bortezomib in inhibiting human 20S proteasome. This candidate also showed good
      activities with IC(50) values nearly less than 5 microM against several human
      solid and hematologic tumor cell lines. Safety evaluation in vivo with zebrafish
      and Sprague-Dawley (SD) rats showed that the candidate 4q was less toxic than
      bortezomib. Pharmacokinetic profiles suggested candidate 4q showed a more plasma
      exposure and longer half-life than bortezomib. Docking results indicated that 4q
      nearly interacted with 20S proteasome in a similar way as bortezomib.

PMID- 20158185
TI  - Cloning, characterization, and inhibition studies of a beta-carbonic anhydrase
      from Brucella suis.
AB  - A beta-carbonic anhydrase (CA, EC 4.2.1.1) from the bacterial pathogen Brucella
      suis, bsCA 1, has been cloned, purified, and characterized kinetically. bsCA 1
      has appreciable activity as catalyst for the hydration of CO(2) to bicarbonate,
      with a k(cat) of 6.4 x 10(5) s(-1) and k(cat)/K(m) of 3.9 x 10(7) M(-1).s(-1). A
      panel of 38 sulfonamides and one sulfamate have been investigated for inhibition
      of this new beta-CA. All types of activities have been detected, with K(I)s in
      the range of 17 nM to 5.87 microM. The best bsCA 1 inhibitors were ethoxzolamide
      (17 nM), celecoxib (18 nM), dorzolamide (21 nM), valdecoxib, and sulpiride (19
      nM). Whether bsCA 1 inhibitors may have application in the fight against
      brucellosis, an endemic disease and the major bacterial zoonosis, producing
      debilitating infection in humans and animals, warrants further studies.

PMID- 20158186
TI  - 1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: a novel series of potent calcium
      sensing receptor antagonists.
AB  - Parathyroid hormone (PTH) is an effective bone anabolic agent. However, only when
      administered by daily sc injections exposure of short duration is achieved, a
      prerequisite for an anabolic response. Instead of applying exogenous PTH,
      mobilization of endogenous stores of the hormone can be envisaged. The secretion
      of PTH stored in the parathyroid glands is mediated by a calcium sensing receptor
      (CaSR) a GPCR localized at the cell surface. Antagonists of CaSR (calcilytics)
      mimic a state of hypocalcaemia and stimulate PTH release to the bloodstream.
      Screening of the internal compound collection for inhibition of CaSR signaling
      function afforded 2a. In vitro potency could be improved >1000 fold by
      optimization of its chemical structure. The binding mode of our compounds was
      predicted based on molecular modeling and confirmed by testing with mutated
      receptors. While the compounds readily induced PTH release after iv application a
      special formulation was needed for oral activity. The required profile was
      achieved by using microemulsions. Excellent PK/PD correlation was found in rats
      and dogs. High levels of PTH were reached in plasma within minutes which reverted
      to baseline in about 1-2 h in both species.

PMID- 20158187
TI  - Fabrication of Ag@SiO(2)@Y(2)O(3):Er nanostructures for bioimaging: tuning of the
      upconversion fluorescence with silver nanoparticles.
AB  - We demonstrated that the nanostructures comprising silver cores and dense layers
      of Y(2)O(3):Er separated by a silica shell are an excellent model system to study
      the interaction between upconversion materials and metals in nanoscale. This
      architecture allows for versatile control of the Y(2)O(3):Er-metal interaction
      through control of the silica dielectric spacer thickness and the metal-core
      size. Finally, the nanoparticles are potentially interesting as fluorescent
      labels in, for instance (single particle), imaging experiments or bioassays which
      require low background or tissue penetrating wavelengths.

PMID- 20158189
TI  - Copper-catalyzed gamma-selective allyl-alkyl coupling between allylic phosphates
      and alkylboranes.
AB  - Copper-catalyzed allyl-alkyl coupling between allylic phosphates and
      alkylboranes, prepared by hydroboration of alkenes with 9-BBN-H, takes place with
      complete gamma- and E-selectivities and with preferential 1,3-anti
      stereochemistry. The reaction tolerates various functional groups in both the
      allylic phosphate and alkylborane. Catalytic mechanisms involving transmetalation
      between a trialkyl(alkoxo)borate and a copper(I) complex to form an
      alkylcopper(I) species are proposed.

PMID- 20158188
TI  - Molecular shape and medicinal chemistry: a perspective.
AB  - The eight contributions here provide ample evidence that shape as a volume or as
      a surface is a vibrant and useful concept when applied to drug discovery. It
      provides a reliable scaffold for "decoration" with chemical intuition (or bias)
      for virtual screening and lead optimization but also has its unadorned uses, as
      in library design, ligand fitting, pose prediction, or active site description.
      Computing power has facilitated this evolution by allowing shape to be handled
      precisely without the need to reduce down to point descriptors or approximate
      metrics, and the diversity of resultant applications argues for this being an
      important step forward. Certainly, it is encouraging that as computation has
      enabled our intuition, molecular shape has consistently surprised us in its
      usefulness and adaptability. The first Aurelius question, "What is the essence of
      a thing?", seems well answered, however, the third, "What do molecules do?", only
      partly so. Are the topics covered here exhaustive, or is there more to come? To
      date, there has been little published on the use of the volumetric definition of
      shape described here as a QSAR variable, for instance, in the prediction or
      classification of activity, although other shape definitions have been successful
      applied, for instance, as embodied in the Compass program described above in
      "Shape from Surfaces". Crystal packing is a phenomenon much desired to be
      understood. Although powerful models have been applied to the problem, to what
      degree is this dominated purely by the shape of a molecule? The shape comparison
      described here is typically of a global nature, and yet some importance must
      surely be placed on partial shape matching, just as the substructure matching of
      chemical graphs has proved useful. The approach of using surfaces, as described
      here, offers some flavor of this, as does the use of metrics that penalize volume
      mismatch less than the Tanimoto, e.g., Tversky measures. As yet, there is little
      to go on as to how useful a paradigm this will be because there is less software
      and fewer concrete results.Finally, the distance between molecular shapes, or
      between any shapes defined as volumes or surfaces, is a metric property in the
      mathematical sense of the word. As yet, there has been little, if any,
      application of this observation. We cannot know what new application to the
      design and discovery of pharmaceuticals may yet arise from the simple concept of
      molecular shape, but it is fair to say that the progress so far is impressive.

PMID- 20158190
TI  - Screening of bimetallic heterogeneous nanoparticle catalysts for arene
      hydrogenation activity under ambient conditions.
AB  - This study focuses on the application of a simple screening approach to prepare
      and test heterogeneous mono- and bimetallic nanoparticle (NP) catalysts for arene
      hydrogenation activity under ambient conditions in a quick and time efficient
      manner, as well as detailed testing and characterization of identified active
      catalysts. Over 90 mono- and bimetallic NP catalysts supported on alumina were
      efficiently screened for arene hydrogenation activity under ambient conditions
      using toluene as a model substrate. Through this approach, four catalysts were
      determined to be active: RhPt/Al(2)O(3), RuPt/Al(2)O(3), IrPt/Al(2)O(3), and
      IrRh/Al(2)O(3). These catalysts were further synthesized and tested in bulk, and
      RhPt/Al(2)O(3) was confirmed to be the catalyst with the highest observed rate of
      all the bimetallic combinations screened. Further studies were then performed,
      and the metal loading, temperature, pressure, and substrate to metal ratios were
      varied to determine the effects of these variables on the activity of the
      RhPt/Al(2)O(3) catalyst and a CS(2) poisoning study was performed on this
      catalyst to determine the number of active sites. From the temperature studies,
      the activation energy was calculated to be 30.4 kJ/mol, which is moderate when
      compared to other arene hydrogenation catalysts (42.0 kJ/mol for the
      hydrogenation of toluene with Ru NPs, (1) and 34.7 and 45.6 kJ/mol for benzene
      hydrogenation with cuboctahedral and cubic Pt NPs, respectively, (2) have been
      reported). Transmission electron microscopy (TEM), X-ray photoelectron
      spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) surface area measurements
      were used to characterize the active catalysts, where it was observed that very
      small zero oxidation state metal NPs were well dispersed throughout the high
      surface area alumina support.

PMID- 20158192
TI  - Reactions of hydridochlorosilanes with 2,2'-bipyridine and 1,10-phenanthroline:
      complexation versus dismutation and metal-catalyst-free 1,4-hydrosilylation.
AB  - Stable in the solid state and isolable in high yields are adducts of H(2)SiCl(2),
      HSiCl(3), and RSiCl(3) (R = Me, Ph) with the N,N'-chelating ligands 1,10
      phenanthroline (phen; 1c), 2,2'-bipyridine (bipy; 1b), and (to a limited extent)
      N,N,N',N'-tetramethylethylenediamine (tmeda; 1a). The products were
      comprehensively characterized via multinuclear solution and solid-state NMR
      spectroscopy, including analysis of the (29)Si NMR chemical shift anisotropy
      tensors, Raman spectroscopy, elemental analyses, and, for SiCl(4)(phen) (2c),
      HSiCl(3)(bipy) (3b), H(2)SiCl(2)(bipy) (4b), MeSiCl(3)(phen) (5c), and
      PhSiCl(3)(phen) (6c), single-crystal X-ray structure analyses. The latter
      revealed that the nonchlorine substituents (i.e., H, Me, and Ph) are exclusively
      trans-disposed to the N-donor atoms of the chelating ligands. A dismutation of
      the complexes HXSiCl(2)(bipy) and HXSiCl(2)(tmeda) (X = H or Cl) was observed in
      polar solvents at elevated temperatures. This reaction is more pronounced when
      phen is used instead of bipy or tmeda. For MeHSiCl(2)(phen), in addition to
      undergoing H-Cl redistribution accompanied by the formation of 5c, an unexpected
      1,4-hydrosilylation was observed. The latter was proven NMR-spectroscopically and
      by a single-crystal X-ray structure analysis of the product MeSiCl(2)(4H-phen)
      (7), a pentacoordinated silicon compound with a trigonal-bipyramidal arrangement
      of the subsituents and the methyl group located in an equatorial position.

PMID- 20158191
TI  - Structural basis for platelet antiaggregation by angiotensin II type 1 receptor
      antagonist losartan (DuP-753) via glycoprotein VI.
AB  - GPVI is a key receptor for collagen-induced platelet activation. Loss or
      inhibition of GPVI causes only mildly prolonged bleeding times but prevents
      arterial thrombus formation in animal models. Therefore, GPVI is considered to be
      a potent target molecule for therapy of thrombotic diseases. Recently, it was
      reported that the AT(1)-receptor antagonist losartan (DuP-753) and EXP3179
      inhibit platelet adhesion and aggregation via GPVI. However, it is still not
      clear how losartan is associated with inhibition of binding between GPVI and
      collagen at the molecular level. Here, we show by NMR that losartan directly
      interacts with the hydrophobic region consisting of strands C' and E in the N
      terminal Ig-like domain of GPVI. A reliable GPVI-losartan complex model is
      presented by using a combination of NMR data and in silico tools. These data
      indicated that the phenyl group with the tetrazole ring in losartan plays a
      crucial role in the interaction with GPVI.

PMID- 20158193
TI  - Microfluidic assays for DNA manipulation based on a block copolymer
      immobilization strategy.
AB  - Methods to manipulate and visualize isolated DNA and oligonucleotide strands are
      important for investigation of their biophysics as well as their interactions
      with proteins. Herein, we report such a method by combining a block copolymer
      surface functionalization strategy with microfluidics. The copolymer poly(l
      lysine-graft-polyethylene glycol) (PLL-g-PEG) coated one surface of the
      microfluidic channels, rendering it passive to adsorption and thus minimizing any
      noise arising from nontargeted adsorbed molecules. Single lambda-phage DNA
      molecules were immobilized and were extended by molecular combing. Their
      extension did not exceed their contour length, which we attribute to the low
      surface tension of the coated surface. To demonstrate further the applicability
      of our method, the anchored DNA was extended by hydrodynamic flow. We propose
      this method for exploring DNA-protein interactions due to the copolymer's
      enhanced capacity for single-molecule detection, stability under wet or dry
      conditions, hydrophilicity, full compatibility with microfluidics and simplicity
      being a one-step process.

PMID- 20158194
TI  - One-step analysis of DNA/chitosan complexes by field-flow fractionation reveals
      particle size and free chitosan content.
AB  - The composition of samples obtained upon complexation of DNA with chitosan was
      analyzed by asymmetrical flow field flow fractionation (AF4) with online UV
      visible, multiangle light scattering (MALS), and dynamic light scattering (DLS)
      detectors. A chitosan labeled with rhodamine B to facilitate UV-vis detection of
      the polycation was complexed with DNA under conditions commonly used for
      transfection (chitosan glucosamine to DNA phosphate molar ratio of 5). AF4
      analysis revealed that 73% of the chitosan-rhodamine remained free in the
      dispersion and that the DNA/chitosan complexes had a broad size distribution
      ranging from 20 to 160 nm in hydrodynamic radius. The accuracy of the data was
      assessed by comparison with data from batch-mode DLS and scanning electron
      microscopy. The AF4 combined with DLS allowed the characterization of small
      particles that were not detected by conventional batch-mode DLS. The AF4 analysis
      will prove to be an important tool in the field of gene therapy because it
      readily provides, in a single measurement, three important physicochemical
      parameters of the complexes: the amount of unbound polycation, the hydrodynamic
      size of the complexes, and their size distribution.

PMID- 20158195
TI  - Inverted colloidal crystal scaffolds for uniform cartilage regeneration.
AB  - A uniform distribution of chondrocytes in 3D scaffolds is a critical challenge to
      cartilage regeneration. This study aims to resolve the problem by showing
      uniformly distributed chondrogenesis in chitin/chitosan matrix with pores of
      inverted colloidal crystal (ICC) structure. The results revealed that the effect
      of solvent on the regularity of colloidal crystal arrays was in the order of
      ethanol > ethylene glycol > acetone. When the concentration of chitin/chitosan
      gel was <2.5%, the porosity of ICC scaffolds with pure ethanol was approximately
      84%. The highly porous freeform scaffolds produced random and unconnected pores,
      in general. The viability of bovine knee chondrocytes (BKCs) in ICC constructs
      was >92%. Over 4 weeks of cultivation, the percentage of biodegradation of ICC
      scaffolds with pure ethanol was approximately 34%. The order in the produced
      BKCs, glycosaminoglycans (GAGs), and collagen was freeform constructs > ICC
      constructs with pure ethanol > ICC constructs with 95% acetone. However, the
      spatial distribution of BKCs in ICC constructs was more uniform than that in
      freeform constructs. In addition, BKCs could secrete GAGs and type II collagen in
      the core of ICC constructs, indicating the maintenance of phenotypic chondrocytes
      and their metabolism. The ICC constructs with well-controlled pore regularity and
      unique topography can generate uniform tissue-engineered cartilage.

PMID- 20158196
TI  - Reactions of organyl and silyl alanes with 1,3,4,5,6-pentamethyl-2-aminoborazine.
AB  - The reactions of (Me(3)Si)(3)Al, Me(3)Al, Et(3)Al, and i-Bu(3)Al with 1,3,4,5,6
      pentamethyl-2-aminoborazine have been examined. An amine alane adduct
      (Me(3)Si)(3)Al.NH(2)B(3)(Me)(2)N(3)Me(3) (1) and several elimination products
      [(Me(3)Si)(2)AlN(H)B(3)(Me)(2)N(3)Me(3)](2) (2), [(Me(3)SiAl)(4)(Me(3)SiN)(3)NH]
      (3), [Me(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (4), [Et(2)AlN(H)
      B(3)(Me)(2)N(3)Me(3)](2) (5), and [i-Bu(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (6)
      have been isolated. Compounds 1, 2, 4-6 have been spectroscopically
      characterized, and single crystal X-ray diffraction structure determinations have
      been completed for 1-4 and 6. The molecular chemistry provides insight into the
      reaction of Me(3)Al and 1,3,5-N-trimethyl-2,4,6-B-triaminoborazine that, upon
      pyrolysis, produces AlN/BN composite ceramic materials.

PMID- 20158197
TI  - How are centrosymmetric and noncentrosymmetric structures achieved in uranyl
      borates?
AB  - Four uranyl borates, UO(2)B(2)O(4) (UBO-1), alpha-(UO(2))(2)[B(9)O(14)(OH)(4)]
      (UBO-2), beta-(UO(2))(2)[B(9)O(14)(OH)(4)] (UBO-3), and
      (UO(2))(2)[B(13)O(20)(OH)(3)].1.25H(2)O (UBO-4), have been prepared from boric
      acid fluxes at 190 degrees C. UBO-3 and UBO-4 are centrosymmetric, whereas UBO-1
      and UBO-2 are noncentrosymmetric (chiral and polar). These uranyl borates possess
      layered structures constructed from UO(8) hexagonal bipyramids, BO(3) triangles,
      and BO(4) tetrahedra. In the case of UBO-4, clusters of BO(3) triangles link the
      layers together to form open slabs with a thickness of almost 2 nm. The ability
      of uranyl borates to use very similar layers to yield both centrosymmetric and
      noncentrosymmetric layers is detailed in this work.

PMID- 20158198
TI  - A time trend study of significantly elevated perfluorocarboxylate levels in
      humans after using fluorinated ski wax.
AB  - A time trend study focusing on ski waxing technicians' exposure to perfluorinated
      chemicals (PFCs) from fluorinated wax fumes was performed in 2007/2008. Levels of
      eight perfluorocarboxylates and three perfluorosulfonates were analyzed in
      monthly blood samples from eight technicians. Samples were collected before the
      ski season, i.e., preseason, then at four FIS World Cup competitions in cross
      country skiing, and finally during an unexposed 5-month postseason period. The
      perfluorinated carboxylates perfluoroheptanoic acid (PFHpA), perfluorooctanoic
      acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and
      perfluoroundecanoic acid (PFUnDA) bioaccumulate, and continued exposure may
      contribute to elevated levels in ski technicians compared to the general
      population. The wax technicians' median blood level of PFOA is 112 ng/mL compared
      to 2.5 ng/mL in the general Swedish population. A significant correlation was
      found between number of working years and levels of perfluorocarboxylates. The
      PFOA levels in three technicians with "low" initial levels of PFOA (<10.0 ng/mL
      in preseason blood) increased by 254, 134, and 120%, whereas five technicians
      with "high" initial levels (>100 ng/mL in preseason sample) were at steady state.
      PFHxA is suggested to have a short half-life in humans relative the other
      perfluorocarboxylates. The levels of perfluorosulfonates were unaffected by the
      wax exposure.

PMID- 20158199
TI  - Role of continuous phase anionic polysaccharides on the oxidative stability of
      menhaden oil-in-water emulsions.
AB  - The antioxidant role of selected polysaccharides was studied in the continuous
      phase of a Menhaden oil-in-water emulsion coated by polyoxyethylene(23) lauryl
      ether (Brij 35) at neutral pH. The addition of low-methoxyl (LM) and high
      methoxyl (HM) pectin (0.02-0.1 wt %) reduced the formation of lipid
      hydroperoxides and thiobarbituric acid reactive substances with an inhibition
      that increased with increasing polysaccharide concentration in the continuous
      phase. alpha-Carrageenan and sodium alginate were less effective antioxidants
      than pectin and were prooxidative under certain conditions. None of the
      polysaccharides impacted the physical properties of the emulsions as determined
      by droplet particle size (d(43) approximately 0.32 microm) and creaming index. LM
      and HM pectins had higher iron-binding capacities as compared to alpha
      carrageenan and sodium alginate, which may relate to their higher antioxidant
      activities. These results suggest that the addition of anionic polysaccharides to
      the continuous phase of oil-in-water emulsions could be used to increase the
      oxidative stability of oil-in-water emulsions and thus prolong shelf life.

PMID- 20158200
TI  - Thermostable variants of pyranose 2-oxidase showing altered substrate selectivity
      for glucose and galactose.
AB  - The homotetrameric flavoprotein pyranose 2-oxidase (P2Ox) has several proposed
      biotechnological applications, among others as a biocatalyst for carbohydrate
      transformations toward higher-value products. To improve some of the catalytic
      properties of P2Ox from Trametes multicolor, we selected a semirational enzyme
      engineering approach, namely, saturation mutagenesis of the amino acid His450
      located at a pivotal point of the active site loop and subsequent screening of
      the libraries thus obtained for improved activity with the sugar substrate d
      galactose. A variant with improved catalytic characteristics identified was
      H450G, which showed a significant, 3.6-fold decrease in K(M) together with a 1.4
      fold increase in k(cat) for its substrate D-galactose and an overall improvement
      in the catalytic efficiency by a factor of 5. By combining H450G with other amino
      acid replacements, we obtained the P2Ox variants H450G/V546C and
      H450G/E542K/V546C, which can be of interest for applications in food industry due
      to their increased activity with D-galactose, high activity with D-glucose, and
      considerably increased stability for the latter variant. While the His-tagged
      recombinant wild-type enzyme strongly prefers D-glucose to D-galactose as its
      substrate, H450G/E542K/V546C converts both sugars, which are found in lactose
      hydrolysates, concomitantly, as was shown by laboratory-scale biotransformation
      experiments. The 2-keto sugars thus obtained can conveniently be reduced to the
      corresponding ketoses D-fructose and D-tagatose.

PMID- 20158201
TI  - Isolation of cellulolytic enzyme lignin from wood preswollen/dissolved in
      dimethyl sulfoxide/n-methylimidazole.
AB  - Attempts were made to enhance polysaccharide digestibility by crude cellulases in
      the isolation of cellulolytic enzyme lignin (CEL) by dissolution of ball-milled
      wood in a dimethyl sulfoxide (DMSO)/N-methylimidazole solvent system as a
      pretreatment step. Wood regenerated from the DMSO/N-methylimidazole solution was
      hydrolyzed with crude cellulases for 48 h, removing 73.7 and 66.9% of the
      original carbohydrate for basswood and loblolly pine, respectively; only 61.7 and
      49.2% were hydrolyzed by the crude cellulases without pretreatment. The yields of
      CEL isolated from regenerated ball-milled wood samples were therefore higher than
      those directly from ball-milled wood material, presumably via decreasing
      crystallinity of cellulose. For basswood, the yields of lignin were 45.8 and
      36.5% (based on Klason lignin); for loblolly pine, the yields were 35.3 and
      30.5%. The isolated lignins were structurally examined using two-dimensional
      heteronuclear single-quantum coherence ((1)H-(13)C HSQC) NMR methods, which
      showed that the main structural characteristics of the lignin fractions obtained
      using these two methods are similar except for slightly higher amounts of
      carbohydrates in the solvent dissolution product.

PMID- 20158202
TI  - Tetranuclear copper(I) iodide complexes of chelating bis(1-benzyl-1H-1,2,3
      triazole) ligands: structural characterization and solid state photoluminescence.
AB  - A series of tetranuclear Cu(4)I(4)(L(n))(2) clusters (1-3) supported by the
      chelating 4,4'-(4,5-diX-1,2-phenylene)bis(1-benzyl-1H-1,2,3-triazole) ligands
      (L1, X = H; L2, X = CH(3); L3, X = F) have been prepared. Crystal structure
      determinations have shown that the clusters adopt a distorted "step-type"
      geometry in which the triazole ligands exhibit both chelating and bridging
      coordination modes to Cu(I) ions. When L3 was employed in a 3:2 CuI/L3 ratio, a
      crystalline product, 4, was obtained. Product 4 is actually a 1:1
      cocrystallization of the tetranuclear cluster 3 (denoted 4a) and the dinuclear
      Cu(2)I(2)(L3)(2) complex (4b). X-ray structures of 1, 2, and 4 show the presence
      of close Cu...Cu contacts in the tetranuclear and dinuclear forms. (1)H NMR
      experiments indicate that rapid exchange occurs in these systems. All clusters
      are brightly luminescent in the solid state at 77 K and at room temperature with
      lambda(max) = 495-524 nm. Emission intensity decays fit a single exponential with
      lifetimes on the order of 10 to 35 microseconds at room temperature and 90 to 140
      microseconds at 77 K. The origin of emission is tentatively assigned as a metal
      to-ligand phenylene pi* charge transfer.

PMID- 20158203
TI  - Structural insights into the design of small molecule inhibitors that selectively
      antagonize Mcl-1.
AB  - The screening of a small focused library of rhodanine derivatives as inhibitors
      of Bcl-2 proteins led to the discovery of two structurally related compounds with
      different binding profiles against the Bcl-XL and the Mcl-1 proteins. Subsequent
      NMR studies with mutant proteins and in silico docking studies provide a possible
      rationale for the observed specificity.

PMID- 20158204
TI  - Synthesis and biological evaluation of bupropion analogues as potential
      pharmacotherapies for smoking cessation.
AB  - Bupropion (2a) analogues were synthesized and tested for their ability to inhibit
      monoamine uptake and to antagonize the effects of human alpha3beta4*,
      alpha4beta2, alpha4beta4, and alpha1* nAChRs. The analogues were evaluated for
      their ability to block nicotine-induced effects in four tests in mice. Nine
      analogues showed increased monoamine uptake inhibition. Similar to 2a, all but
      one analogue show inhibition of nAChR function selective for human alpha3beta4*
      nAChR. Nine analogues have higher affinity at alpha3beta4*-nAChRs than 2a. Four
      analogues also had higher affinity for alpha4beta2 nAChR. Analogues 2r, 2m, and
      2n with AD(50) values of 0.014, 0.015, and 0.028 mg/kg were 87, 81, and 43 times
      more potent than 2a in blocking nicotine-induced antinociception in the tail
      flick test. Analogue 2x with IC(50) values of 31 and 180 nM for DA and NE,
      respectively, and with IC(50) of 0.62 and 9.8 microm for antagonism of
      alpha3beta4 and alpha4beta2 nAChRs had the best overall in vitro profile relative
      to 2a.

PMID- 20158205
TI  - Hybrid molecules from xanomeline and tacrine: enhanced tacrine actions on
      cholinesterases and muscarinic M1 receptors.
AB  - A set of amide- and amine-linked hybrid molecules comprising moieties of the
      orthosteric M(1) muscarinic receptor agonist xanomeline and the cholinesterase
      inhibitor and allosteric receptor modulator tacrine were prepared with varying
      spacer length of 10-17 atoms. The hybrids inhibited acetylcholinesterase with
      similar or higher potency compared to tacrine. M(1) receptor binding affinity was
      similar or higher relative to xanomeline and far higher relative to tacrine.
      Affinities hardly changed when the receptors' orthosteric site was occupied by an
      inverse agonist ligand. When occupied by the orthosteric activator acetylcholine,
      affinity for the hybrids declined to unmeasureably low levels. Hybrids did not
      activate M(1) receptors. In vivo studies assaying cognition impairment in rats
      induced by scopolamine revealed pronounced enhancement of scopolamine action.
      Taken together, instead of dualsteric (simultaneous allosteric/orthosteric)
      binding, the hybrids seem to prefer purely allosteric binding at the inactive
      M(1) receptor.

PMID- 20158206
TI  - Inhibitory kinetics of betaine on beta-N-acetyl-D-glucosaminidase from prawn
      (Litopenaeus vannamei).
AB  - The effects of betaine on prawn beta-N-acetyl-D-glucosaminidase (NAGase) activity
      for the hydrolysis of p-nitrophenyl-N-acetyl- beta-D-glucosaminide (pNP-NAG) have
      been studied. The results showed that appropriate concentrations of betaine could
      lead to reversible inhibition against NAGase, and the IC(50) value was estimated
      to be 15.00 +/- 0.30 mM. The inhibitory kinetics assay showed that betaine was a
      mixed type inhibitor with a K(I) value of 9.17 +/- 0.85 mM and a K(IS) value of
      45.58 +/- 2.52 mM. The inhibitory model was set, and the microscopic rate
      constants were determined using the kinetic method of the substrate reaction. The
      time course of the hydrolysis of pNP-NAG catalyzed by NAGase in the presence of
      different betaine concentrations showed that at each betaine concentration, the
      rate decreased with an increase in time until a straight line was approached,
      indicating that the inhibition of NAGase by betaine is a slow, reversible
      reaction with fractional residual activity. The fact that k(+0) is much larger
      than k(+0)(') indicated that the free enzyme molecule is more fragile than the
      enzyme-substrate complex against betaine. It is suggested that the presence of
      the substrate offers marked protection of NAGase against inhibition by betaine.

PMID- 20158207
TI  - Effect of reductive property of activated carbon on total organic halogen
      analysis.
AB  - Total organic halogen (TOX) is a collective parameter and a toxicity indicator
      for all the halogenated organic disinfection byproducts (DBPs) in a water sample.
      TOX can be measured with the adsorption-pyrolysis method based on Standard Method
      5320B. This method involves concentration of organic halogens from water by
      adsorption onto activated carbon (AC) and removal of inorganic halides present on
      the AC by competitive displacement by nitrate ions. Since AC can also act as a
      reductant, this work studied whether the reduction of chlorinated DBPs by AC
      occurs during the TOX measurement, to what extent the reduction affects the
      measurement of TOX, what type of chlorinated DBPs can be reduced by AC, and
      whether the method for the TOX measurement can be improved. Initially,
      chlorinated Suwannee River fulvic acid samples were prepared and pretreated with
      precipitation/dialysis/ultrafiltration to minimize the chloride levels in the
      samples. It was found that the fractions of TOX in the precipitated, dialyzed,
      and ultrafiltered samples that were reduced by AC in 5 min were around 13%, 20%
      and 24%, respectively. The formation of some N-chloroamino compounds and their
      reactivity with AC were examined. The results indicate that organic chloramines
      are one type of DBPs in TOX that could be reduced by AC. It was demonstrated that
      slight oxidation of AC with ozone basically inhibited its reduction for TOX and
      meanwhile maintained its adsorption capacity for TOX.

PMID- 20158208
TI  - Ethanol production from orange peels: two-stage hydrolysis and fermentation
      studies using optimized parameters through experimental design.
AB  - Orange peels were evaluated as a fermentation feedstock, and process conditions
      for enhanced ethanol production were determined. Primary hydrolysis of orange
      peel powder (OPP) was carried out at acid concentrations from 0 to 1.0% (w/v) at
      121 degrees C and 15 psi for 15 min. High-performance liquid chromatography
      analysis of sugars and inhibitory compounds showed a higher production of
      hydroxymethyfurfural and acetic acid and a decrease in sugar concentration when
      the acid level was beyond 0.5% (w/v). Secondary hydrolysis of pretreated biomass
      obtained from primary hydrolysis was carried out at 0.5% (w/v) acid. Response
      surface methodology using three factors and a two-level central composite design
      was employed to optimize the effect of pH, temperature, and fermentation time on
      ethanol production from OPP hydrolysate at the shake flask level. On the basis of
      results obtained from the optimization experiment and numerical optimization
      software, a validation study was carried out in a 2 L batch fermenter at pH 5.4
      and a temperature of 34 degrees C for 15 h. The hydrolysate obtained from primary
      and secondary hydrolysis processes was fermented separately employing parameters
      optimized through RSM. Ethanol yields of 0.25 g/g on a biomass basis (YP/X) and
      0.46 g/g on a substrate-consumed basis (YP/S) and a promising volumetric ethanol
      productivity of 3.37 g/L/h were attained using this process at the fermenter
      level, which shows promise for further scale-up studies.

PMID- 20158209
TI  - General quantification of catchment-scale nutrient and pollutant transport
      through the subsurface to surface and coastal waters.
AB  - This study develops a general quantification framework for consistent intermodel
      and intercatchment comparison of the nutrient and pollutant mass loading from
      multiple sources in a catchment area to downstream surface and coastal waters.
      The framework accounts for the wide spectrum of different transport pathways and
      travel times through the subsurface (soil, groundwater, sediment) and the linked
      surface (streams, lakes, wetlands) water systems of a catchment. The account is
      based on key flow partitioning and mass delivery fractions, which can be
      quantified differently by different flow and transport and reaction models. The
      framework application is exemplified for two Swedish catchment cases with regard
      to the transport of phosphorus and of a generic attenuating solute. The results
      show essential differences in model quantifications of transport pathways and
      temporal spreading, with important implications for our understanding of cause
      and effect in the catchment-scale nutrient and pollutant loading to downstream
      waters.

PMID- 20158210
TI  - Determination of copper in clarified apple juices.
AB  - Inorganic copper compounds are not considered as synthetic fertilizers for apple
      trees as they are traditional fertilizers. Thus, they are used in organic farming
      for soil or foliar applications. The European Union is for health reasons
      interested in reducing copper in apple orchards. Because the fertilizer
      application rate affects the nutrition of apples, the applied copper might also
      be reflected in the copper concentration of apple juices. Thus, the determination
      of copper is of concern for investigating the application of copper-containing
      fertilizers. Samples of clarified apple juice commercially available in the
      European market were analyzed for their copper content. Prior to quantification
      by inductively coupled plasma-optical emission spectrometry, the juices were
      processed by a microwave-assisted digestion system using HNO(3). All samples were
      also measured directly after dilution with HNO(3). The copper concentrations
      measured using both methods were all below the limit of detection (17 microg/L).

PMID- 20158212
TI  - Impact of genetics and environment on the metabolite composition of maize grain.
AB  - This study sought to assess genetic and environmental impacts on the metabolite
      composition of maize grain. Gas chromatography coupled to time-of-flight mass
      spectrometry (GC-TOF-MS) measured 119 identified metabolites including free amino
      acids, free fatty acids, sugars, organic acids, and other small molecules in a
      range of hybrids derived from 48 inbred lines crossed against two different
      tester lines (from the C103 and Iodent heterotic groups) and grown at three
      locations in Iowa. It was reasoned that expanded metabolite coverage would
      contribute to a comprehensive evaluation of the grain metabolome, its degree of
      variability, and, in principle, its relationship to other compositional and
      agronomic features. The metabolic profiling results established that the small
      molecule metabolite pool is highly dependent on genotypic variation and that
      levels of certain metabolite classes may have an inverse genotypic relationship
      to each other. Different metabolic phenotypes were clearly associated with the
      two distinct tester populations. Overall, grain from the C103 lines contained
      higher levels of free fatty acids and organic acids, whereas grain from the
      Iodent lines were associated with higher levels of amino acids and carbohydrates.
      In addition, the fold-range of genotype mean values [composed of six samples each
      (two tester crosses per inbred x three field sites)] for identified metabolites
      ranged from approximately 1.5- to 93-fold. Interestingly, some grain metabolites
      showed a non-normal distribution over the entire corn population, which could, at
      least in part, be attributed to large differences in metabolite values within
      specific inbred crosses relative to other inbred sets. This study suggests a
      potential role for metabolic profiling in assisting the process of selecting
      elite germplasm in biotechnology development, or marker-assisted breeding.

PMID- 20158213
TI  - Peptide-catalyzed kinetic resolution of formamides and thioformamides as an entry
      to nonracemic amines.
AB  - We report a fundamentally unique approach to the catalytic kinetic resolution of
      amine derivatives based on formamide and thioformamide substrates. Readily
      accessible histidine-containing peptides mediate the kinetic resolutions with as
      little as 5 mol % catalyst. Selectivity factors (k(rel)) as high as 43.7 were
      observed under simple reaction conditions utilizing Boc(2)O as the reagent at
      room temperature. Mechanistic experiments were conducted that established a
      higher level of reactivity for thioformamide substrates than for their formamide
      analogues. The products of these asymmetric reactions were shown to be readily
      converted to desirable building blocks such as N-Boc-amines and the parent chiral
      formamide compounds.

PMID- 20158215
TI  - Bridged beta(3)-peptide inhibitors of p53-hDM2 complexation: correlation between
      affinity and cell permeability.
AB  - Beta-peptides possess several features that are desirable in peptidomimetics;
      they are easily synthesized, fold into stable secondary structures in physiologic
      buffers, and resist proteolysis. They can also bind to a diverse array of
      proteins to inhibit their interactions with alpha-helical ligands. beta-peptides
      are usually not cell-permeable, however, and this feature limits their utility as
      research tools and potential therapeutics. Appending an Arg(8) sequence to a beta
      peptide improves uptake but adds considerable mass. We previously reported that
      embedding a small cationic patch within a PPII, alpha-, or beta-peptide helix
      improves uptake without the addition of significant mass. In another mass-neutral
      strategy, Verdine, Walensky, and others have reported that insertion of a
      hydrocarbon bridge between the i and i + 4 positions of an alpha-helix also
      increases cell uptake. Here we describe a series of beta-peptides containing
      diether and hydrocarbon bridges and compare them on the basis of cell uptake and
      localization, affinities for hDM2, and 14-helix structure. Our results highlight
      the relative merits of the cationic-patch and hydrophobic-bridge strategies for
      improving beta-peptide uptake and identify a surprising correlation between
      uptake efficiency and hDM2 affinity.

PMID- 20158217
TI  - Synthesis and properties of tetracyanamidosilicates ARE[Si(CN2)4].
AB  - Tetracyanamidosilicates of the type ARE[Si(CN(2))(4)] with A = K, Rb, and Cs and
      RE = Y and La-Lu have been prepared by a solid-state metathesis reaction. The
      potassium compounds with RE = La-Gd crystallize orthorhombically in the space
      group P2(1)2(1)2. Rubidium as well as cesium compounds crystallize tetragonally
      in the space group I4. The luminescent properties of ARE[Si(CN(2))(4)]:Ln
      compounds with RE = Y, La, and Gd doped with 5 mol % Ln = Ce, Eu, or Tb were
      investigated. Temperature-dependent magnetic susceptibilities were measured for
      KGd[Si(CN(2))(4)]. The value of the magnetic moment is 7.3 mu(B)/Gd(3+) ion,
      which is in line with the expected value for the [Xe]4f(7) configuration of
      Gd(3+).

PMID- 20158216
TI  - Submicrometer plate heights for capillaries packed with silica colloidal
      crystals.
AB  - Extremely uniform packing of colloidal silica in capillaries is shown. Reversed
      phase electrochromatograms of DiI-C(12) exhibit plate heights as low as 0.23
      microm and a reduced plate height as low as 0.7, using 75 microm i.d. capillaries
      packed with 330 nm silica particles. The contribution from the A term is 0 +/- 20
      nm in electrochromatography. The particles are shown to form colloidal crystals
      inside the capillaries. Optical images show Bragg diffraction, indicative of
      crystallinity. Scanning electron microscopy (SEM) images show face-centered cubic
      crystallinity, and the porosity is 0.25 +/- 0.01, which is in agreement with that
      for face-centered cubic crystals. The capillaries are fritless, and 100 microm
      i.d. capillaries packed with silica colloidal crystals withstand pressures of at
      least 12,400 psi.

PMID- 20158219
TI  - Synthesis of 4-methyldienoates using a vinylogous Horner-Wadsworth-Emmons
      reagent. Application to the synthesis of trichostatic acid.
AB  - The utility of the unsaturated phosphonate 1 as a vinylogous Horner-Wadsworth
      Emmons reagent was explored in reactions with aldehydes affording 4
      methyldienoate esters. Factors that affect E/Z selectivity were studied. A
      simplified synthesis of trichostatic acid 3 was accomplished to demonstrate
      utility of this reagent.

PMID- 20158220
TI  - Direct and selective functionalization of a tetrahydro-beta-carboline at position
      4.
AB  - The first example of direct functionalization of a tetrahydro-beta-carboline
      (THBC) at position 4 is presented. Nucleophiles with various reactivity add to a
      transient intermediate generated in situ from this THBC. This reaction proceeds
      with a total control of the two created stereogenic centers.

PMID- 20158218
TI  - Self-assembling multidomain peptide hydrogels: designed susceptibility to
      enzymatic cleavage allows enhanced cell migration and spreading.
AB  - Multidomain peptides are a class of amphiphilic self-assembling peptides with a
      modular ABA block motif in which the amphiphilic B block drives self-assembly
      while the flanking A blocks, which are electrostatically charged, control the
      conditions under which assembly takes place. Previously we have shown that
      careful selection of the amino acids in the A and B blocks allow one to control
      the self-assembled fiber length and viscoelastic properties of formed hydrogels.
      Here we demonstrate how the modular nature of this peptide assembler can be
      designed for biological applications. With control over fiber length and
      diameter, gelation conditions, and viscoelastic properties, we can develop
      suitable materials for biological applications. Going beyond a simple carrier for
      cell delivery, a biofunctional scaffold will interact with the cells it carries,
      promoting advantageous cell-matrix interactions. We demonstrate the design of a
      multidomain peptide into a bioactive variant by incorporation of a matrix
      metalloprotease 2 (MMP-2) specific cleavage site and cell adhesion motif. Gel
      formation and rheological properties were assessed and compared to related
      peptide hydrogels. Proteolytic degradation by collagenase IV was observed in a
      gel weight loss study and confirmed by specific MMP-2 degradation monitored by
      mass spectrometry and cryo-transmission electron microscopy (cryo-TEM).
      Combination of this cleavage site with the cell adhesion motif RGD resulted in
      increased cell viability and cell spreading and encouraged cell migration into
      the hydrogel matrix. Collectively the structural, mechanical, and bioactive
      properties of this multidomain peptide hydrogel make it suitable as an injectable
      material for a variety of tissue engineering applications.

PMID- 20158221
TI  - The assembly of a multisubunit photosynthetic membrane protein complex: a site
      specific spin labeling EPR spectroscopic study of the PsaC subunit in photosystem
      I.
AB  - The assembly of the PsaC subunit in the photosystem I (PS I) complex was studied
      using site-specific spin labeling electron paramagnetic resonance (EPR)
      spectroscopic techniques. The binding was monitored from the perspective of a
      reporter spin label attached to either the native C34(C) or the engineered C75(C)
      residue of wild-type PsaC (PsaC(WT)). Three distinct stages of PsaC assembly were
      analyzed: unbound PsaC, the P(700)-F(X)/PsaC complex, and the P(700)
      F(X)/PsaC/PsaD complex. The changes in the EPR spectral line shape and the
      rotational correlation time of the spin label when PsaC(WT) binds to the PS I
      core are consistent with the conformational changes that are expected to occur
      during the assembly process. The addition of the PsaD subunit to the P(700)
      F(X)/PsaC(WT-C34) complex induces further EPR spectral changes, which indicate
      that the presence of PsaD affects the orientation of the PsaC subunit on the PS I
      core. The binding of several PsaC variants, each lacking one or more key binding
      contacts with the PsaA/PsaB heterodimer, was monitored using a reporter spin
      label at C34(C). Our results indicate that the absence of the PsaC-PsaA/PsaB
      binding contacts causes PsaC to bind in an altered configuration on the PS I
      core. In particular, the removal of the entire C-terminus (PsaC(C-term)) causes
      PsaC to dock in a significantly different orientation when compared to the wild
      type protein, as indicated by the EPR spectrum of the P(700)-F(X)/PsaC(C-term
      C34) complex. Because the PsaC(C-term) variant retains only the symmetric network
      of PsaC-PsaA/PsaB ionic contacts, the altered EPR spectrum could, in principle,
      reflect a fraction of reaction centers that contain PsaC bound in the 180 degrees
      rotated, C(2)-symmetry-related configuration. The results of this study are used
      to provide a comprehensive, stepwise mechanism for the binding of PsaC on the PS
      I core.

PMID- 20158222
TI  - Composites of metal nanoparticles and TiO2 immobilized in spherical
      polyelectrolyte brushes.
AB  - The synthesis and the catalytic activity of nanocomposites consisting of metal
      nanoparticles (Au, Pt, Pd) and nanoparticles of TiO(2) (anatase) is presented.
      These composite particles have been synthesized by reduction of the respective
      metal ions adsorbed on the surface of as-prepared TiO(2) nanoparticles that are
      immobilized on spherical polyelectrolyte brush particles (SPB) as carrier system.
      The SPB particles consist of a polystyrene core from which long chains of
      poly(styrene sodium sulfonate) are grafted. We demonstrate that the metal
      nanoparticles (such as Au, Pt, and Pd) are only generated on the surface of the
      anatase particles having a size of ca. 10 nm. These metal NP/TiO(2)@SPB composite
      particles exhibit a high colloidal stability. They are excellent heterogeneous
      photocatalysts for the degradation of the dye Rhodamine B under UV irradiation.
      The photocatalytic activity of the composite particles is 2-5 times higher than
      that of the pure TiO(2) particles. This finding is traced back to an enhanced
      adsorption of the dye on the metal@TiO(2) composites.

PMID- 20158223
TI  - Preparation of micrometer-sized, onionlike multilayered block copolymer particles
      by two-step AGET ATRP in aqueous dispersed systems: effect of the second-step
      polymerization temperature.
AB  - The polymerization rate, control/livingness, and particle morphology in seeded
      activators generated by electron transfer for the atom-transfer radical
      polymerization of styrene with PiBMA-Br macroinitiator particles were
      investigated at 70, 90, and 110 degrees C. At 110 degrees C, the polymerization
      proceeded quickly until 60% conversion was reached, but control/livingness was
      not observed. This seems to be the reason for the high activation rate and
      spontaneous initiation of styrene, which significantly increased the radical
      concentration, resulting in a number of radical terminations. As a result, the
      block copolymer was not sufficiently formed, leading to a sea-island structure.
      However, at 70 and 90 degrees C, the polymerizations were almost complete in 14
      and 7 h, respectively. Control/livingness was maintained, resulting in PiBMA-b
      PS. As a result, onionlike multilayered particles were successfully synthesized.
      These polymerization behaviors were discussed from the viewpoint of the radical
      concentration and propagation rate coefficient at various temperatures.

PMID- 20158224
TI  - Morphology and self-arraying of SDS and DTAB dried on mica surface.
AB  - Dewetting phenomena produce interesting patterns that may impart new properties
      to solid surfaces. Sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium
      bromide (DTAB) aqueous solutions, dried on mica surfaces under different drying
      conditions, undergo dewetting events forming structured deposits that were imaged
      by scanning electron microscopy (SEM), atomic force (AFM) and Kelvin force
      microscopy (KFM). Dry SDS, in most situations, displays long branched stripes
      formed due to fingering instability, while DTAB undergoes stick-slip motion
      forming patterns of parallel continuous or split stripes. In both systems,
      independently of drying conditions, surfactants pack forming lamellar structures,
      but with different orientations: SDS lamellae are aligned parallel to the
      substrate whereas DTAB lamellae are normal to the mica plane. Electric potential
      maps of SDS obtained by KFM show well-defined electrostatic patterns: surfactant
      layers deposited on mica are overall negative with a larger excess of negative
      charge in the interlamellar space than in the lamellar faces.

PMID- 20158225
TI  - A rapid methodology for the characterization of dialkyl tertiary amine-N-oxide
      metabolites using structurally dependent dissociation pathways and reconstructed
      ion current chromatograms.
AB  - A high-performance liquid chromatography-electrospray ionization-tandem mass
      spectrometry (HPLC-ESI-MS/MS) approach to the characterization of dialkyl
      tertiary amine-N-oxides is presented. The methodology is based upon forming
      reconstructed ion current chromatograms (RICCs) of m/z values of product ions
      known to form through diagnostic losses from dialkyl tertiary amine-N-oxides. The
      diagnostic losses of N,N-dimethylhydroxylamine and N,N-diethylhydroxylamine were
      identified through the analysis of a structurally diverse library of compounds by
      ESI-low-energy collision-induced dissociation (CID)-MS/MS using quadrupole ion
      trap-mass spectrometry (QIT-MS) and quadrupole time-of-flight-mass spectrometry
      (QqTOF-MS). The library consisted of dialkyl tertiary amine-containing
      commercially available pharmaceuticals, along with a number of model, synthetic N
      oxides. The loss of the nitrogen-containing group was observed in 89% of the low
      energy CID product ion spectra acquired using various collision energies.
      Further, the resultant product ions, formed through the loss of the nitrogen
      containing group, were shown to be unstable because of the observation of second
      generation dissociation. These observations regarding gas-phase ion chemistry
      could be useful to developers of in silico programs for fragmentation prediction
      by allowing the creation of improved algorithms and models for predicting
      dissociation. Using the information derived from the library analysis, the
      characterization methodology was developed and demonstrated using tetracaine. The
      approach is rapid, MS/MS platform independent, utilizes existing technology, and
      could be automated. Further, it is definitive and overcomes the limitations of
      other tools for N-oxide identification by localizing the site of oxidation. Thus,
      it provides a useful addition to the existing approaches for metabolite
      identification.

PMID- 20158226
TI  - Development, characterization, and application of paper spray ionization.
AB  - Paper spray is developed as a direct sampling ionization method for mass
      spectrometric analysis of complex mixtures. Ions of analyte are generated by
      applying a high voltage to a paper triangle wetted with a small volume (<10
      microL) of solution. Samples can be preloaded onto the paper, added with the
      wetting solution, or transferred from surfaces using the paper as a wipe. It is
      demonstrated that paper spray is applicable to the analysis of a wide variety of
      compounds, including small organic compounds, peptides, and proteins. Procedures
      are developed for analysis of dried biofluid spots and applied to therapeutic
      drug monitoring with whole blood samples and to illicit drug detection in raw
      urine samples. Limits of detection of 50 ng/mL (or 20 pg absolute) are achieved
      for atenolol in bovine blood. The combination of sample collection from surfaces
      and paper spray ionization also enables fast chemical screening at high
      sensitivity, for example 100 pg of heroin distributed on a surface and
      agrochemicals on fruit peels are detectable. Online derivatization with a
      preloaded reagent is demonstrated for analysis of cholesterol in human serum. The
      combination of paper spray with miniature mass spectrometers offers a powerful
      impetus to wide application of mass spectrometry in nonlaboratory environments.

PMID- 20158227
TI  - Preparation of "mushroom-like" Janus particles by site-selective surface
      initiated atom transfer radical polymerization in aqueous dispersed systems.
AB  - A versatile approach for the preparation of micrometer-sized, monodisperse,
      "mushroom-like" Janus polymer particles in aqueous dispersed systems is proposed.
      The synthetic methodology of the Janus particles consists of the following two
      steps. The first step is the preparation of spherical poly(methyl methacrylate)
      (PMMA)/poly(styrene-2-(2-bromoisobutyryloxy)ethyl methacrylate) (P(S-BIEM)) Janus
      particles based on the internal phase separation induced by solvent evaporation
      from the solvent droplets dissolving the polymers. The second step is surface
      initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl
      methacrylate (DM) using the Janus particles with ATRP initiator groups at one
      side of the surface as macroinitiator. As a consequence, mushroom-like PMMA/P(S
      BIEM)-graft-poly(DM) Janus particles were prepared, which had pH-responsive
      property.

PMID- 20158228
TI  - Second harmonic generation study of malachite green adsorption at the interface
      between air and an electrolyte solution: observing the effect of excess
      electrical charge density at the interface.
AB  - Understanding the differential adsorption of ions at the interface of an
      electrolyte solution is very important because it is closely related, not only to
      the fundamental aspects of biological systems, but also to many industrial
      applications. We have measured the excess interfacial negative charge density at
      air-electrolyte solution interfaces by using resonant second harmonic generation
      of oppositely charged probe molecules. The excess charge density increased with
      the square root of the bulk electrolyte concentration. A new adsorption model
      that includes the electrostatic interaction between adsorbed molecules is
      proposed to explain the measured adsorption isotherm, and it is in good agreement
      with the experimental results.

PMID- 20158230
TI  - Binding of silver nanoparticles to bacterial proteins depends on surface
      modifications and inhibits enzymatic activity.
AB  - Here we describe results from a proteomic study of protein-nanoparticle
      interactions to further the understanding of the ecotoxicological impact of
      silver nanoparticles (AgNPs) in the environment. We identified a number of
      proteins from Escherichia coli that bind specifically to bare or carbonate-coated
      AgNPs. Of these proteins, tryptophanase (TNase) was observed to have an
      especially high affinity for both surface modifications despite its low abundance
      in E. coli. Purified TNase loses enzymatic activity upon associating with AgNPs,
      suggesting that the active site may be in the vicinity of the binding site(s).
      TNase fragments with high affinities for both types of AgNPs were identified
      using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry. Differences in peptide abundance/presence in mass spectra for the
      two types of AgNPs suggest preferential binding of some protein fragments based
      on surface coating. One high-binding protein fragment contained a residue
      (Arg103) that is part of the active site. Ag adducts were identified for some
      fragments and found to be characteristic of strong binding to AgNPs rather than
      association of the fragments with ionic silver. These results suggest a probable
      mechanism for adhesion of proteins to the most commonly used commercial
      nanoparticles and highlight the potential effect of nanoparticle surface coating
      on bioavailability.

PMID- 20158229
TI  - Identification of antibiotic-resistance-gene molecular signatures suitable as
      tracers of pristine river, urban, and agricultural sources.
AB  - Animal feeding operations (AFOs) and wastewater treatment plants (WWTPs) are
      potential sources of antibiotic resistance genes (ARGs) in rivers and/or
      antibiotics that may select for ARGs in native river bacteria. This study aimed
      to identify ARG distribution patterns that unambiguously distinguish putative
      sources of ARG from a native river environment. Such molecular signatures may
      then be used as tracers of specific anthropogenic sources. Three WWTPs, six AFO
      lagoons, and three sites along a pristine region of the Cache la Poudre (Poudre)
      River were compared with respect to the frequency of detection (FOD) of 11
      sulfonamide and tetracycline ARGs. Principle-component and correspondence
      analyses aided in identifying the association of tet(H), tet(Q), tet(S), and
      tet(T) (tet group HQST) with AFO environments and tet(C), tet(E), and tet(O) (tet
      group CEO) with WWTPs. Discriminant analysis indicated that both tet group HQST
      and tet group CEO correctly classified the environments, but only the tet group
      HQST provided a significant difference in FOD among the environments (p < 0.05).
      Sul(I) was detected in 100% of the source environments but just once in the
      pristine Poudre River, which was dominated by tet(M) and tet(W). Tet(W) libraries
      generated from the pristine Poudre River, WWTPs, and AFO lagoons were also
      discernible based on restriction fragment length polymorphism and phylogenetic
      analysis. Thus, a novel approach was developed and demonstrated to be effective
      for the model river system, taking an important step in advancing the fundamental
      understanding of ARG transport in the environment.

PMID- 20158231
TI  - Diurnal and seasonal variations of ultrafine particle formation in anthropogenic
      SO2 plumes.
AB  - The cloud condensation nuclei concentrations predicted by global aerosol models
      are sensitive to how new particle formation in subgrid anthropogenic SO(2) plumes
      is parameterized. Using a state-of-the-art kinetic nucleation model, we carried
      out two case studies to investigate the large difference in the number
      concentrations of ultrafine particles observed in the plumes from the Horne
      smelter: one in the summer and the other in the winter. Our model predicted that
      particle number concentrations are in good agreement with observations for both
      cases, showing that particle formation in the Horne smelter plumes is dominated
      by binary homogeneous nucleation (BHN) in the winter case and by ion-mediated
      nucleation (IMN) in the summer case. Further sensitivity studies reveal
      significant diurnal and seasonal variations of sulfate particle formation in the
      anthropogenic SO(2) plume, mainly associated with corresponding variations of two
      key parameters: hydroxyl radical concentration ([OH]) and temperature. Nucleation
      in the plume is negligible at night because of very low [OH]. BHN is significant
      when [OH] is relatively high or temperature is relatively low, and it is
      generally limited to the fresh plumes (within approximately 15 km from source),
      but it can generate very high concentrations of ultrafine particles (peak values
      as high as 10(5)-10(6) cm(-3)) under favorable conditions. IMN generally
      dominates nucleation in the plume when [OH] is relatively low or temperature is
      relatively high, and it extends from fresh plume to more aged plume and produces
      2-3 x 10(4) cm(-3) of nucleated particles. The implications of the results are
      discussed.

PMID- 20158232
TI  - Timing of increased autistic disorder cumulative incidence.
AB  - Autistic disorder (AD) is a severe neurodevelopmental disorder typically
      identified in early childhood. Both genetic and environmental factors are
      implicated in its etiology. The number of individuals identified as having autism
      has increased dramatically in recent years, but whether some proportion of this
      increase is real is unknown. If real, susceptible populations may have exposure
      to controllable exogenous stressors. Using literature AD data from long-term
      (approximately 10-year) studies, we determined cumulative incidence of AD for
      each cohort within each study. These data for each study were examined for a
      changepoint year in which the AD cumulative incidence first increased. We used
      data sets from Denmark, California, Japan, and a worldwide composite of studies.
      In the Danish, California, and worldwide data sets, we found that an increase in
      AD cumulative incidence began about 1988-1989. The Japanese study (1988-1996) had
      AD cumulative incidence increasing continuously, and no changepoint year could be
      calculated. Although the debate about the nature of increasing autism continues,
      the potential for this increase to be real and involve exogenous environmental
      stressors exists. The timing of an increase in autism incidence may help in
      screening for potential candidate environmental stressors.

PMID- 20158233
TI  - Comparative survey of conducting polymers containing benzene, naphthalene, and
      anthracene cores: interplay of localized aromaticity and polymer electronic
      structures.
AB  - We present a systematic study to understand to what extent the localization of
      aromaticity in an orthogonal sense to the main polymer conjugation pathway will
      influence the observed optical and electrical properties as the polymers undergo
      oxidation and doping into conductive materials. Three classes of
      electropolymerizable monomers were prepared where the critical electronic unit
      was chosen to foster different degrees of aromatic localization pendant to the
      conjugation pathway: specifically, those based upon benzene, naphthalene, and
      anthracene cores. The expectation was that the benzene unit would foster
      extensive intramolecular delocalization upon adoption of the quinoidal electronic
      structure on account of the strong polyene character. On the other hand,
      resonance contributors can be rationalized for naphthalene and anthracene whereby
      one or two aromatic sextets evolve within the quinoidal structure thereby leading
      to a more localized electronic structure. Monomer and polymer electronics were
      probed with UV-vis spectroscopy and cyclic voltammetry as well as through in situ
      profiling of the conductive states of the respective polymers. A semiempirical
      analysis of the frontier orbital wave functions was employed to further
      understand the influences of competing aromaticity pendant to the polymer
      backbones. Our findings indicate the potential for complex and tunable pi
      conjugated polymers whose properties can be externally controlled through local
      alterations of aromatic character within units fused or cross-conjugated to
      polymer main chains.

PMID- 20158234
TI  - Probing selected morphological models of hydrated Nafion using large-scale
      molecular dynamics simulations.
AB  - Atomistic molecular dynamics simulations were performed to study hydrated Nafion
      systems large enough (approximately 2 million atoms, approximately 30 nm box
      length) to directly observe several hydrophilic domains at the molecular level.
      These systems consisted of six of the most significant and relevant morphological
      models of Nafion to-date: (1) the cluster-channel model, (2) the parallel
      cylinder model, (3) the local order model, (4) the lamellar model, (5) the rod
      network model, and (6) a "random" model that does not directly assume any
      particular geometry, distribution, or morphology. Each system was initially built
      to closely approximate the proposed hydrophilic cluster structure in a given
      model. Molecular dynamics simulations were then used to observe resulting changes
      from and behavior of the assumed initial configurations. These simulations
      revealed fast intercluster "bridge" formation and network percolation in all
      models. Sulfonate groups were found inside these bridges and played a significant
      role in percolation. Sulfonates also strongly aggregated around and inside
      clusters. Cluster surfaces were analyzed to study the hydrophilic-hydrophobic
      interface. Interfacial area and cluster volume significantly increased during the
      simulations, and radial distribution functions and structure factors were also
      calculated. All nonrandom models clearly exhibited the characteristic
      experimental scattering peak, underscoring the insensitivity of this measurement
      to hydrophilic domain structure and highlighting the need for future work to
      clearly distinguish morphological models of Nafion.

PMID- 20158235
TI  - Synthesis of diketopyrrolopyrrole containing copolymers: a study of their optical
      and photovoltaic properties.
AB  - The diketopyrrolopyrrole-based copolymers PDPP-BBT and TDPP-BBT were synthesized
      and used as a donor for bulk heterojunction photovoltaic devices. The
      photophysical properties of these polymers showed absorption in the range 500-600
      nm with a maximum peak around 563 nm, while TDPP-BBT showed broadband absorption
      in the range 620-800 nm with a peak around 656 nm. The power conversion
      efficiencies (PCE) of the polymer solar cells based on these copolymers and [6,6]
      phenyl C61 butyric acid methyl ester (PCBM) were 0.68% (as cast PDPP-BBT:PCBM),
      1.51% (annealed PDPP-BBT:PCBM), 1.57% (as cast TDPP-BBT:PCBM), and 2.78%
      (annealed TDPP-BBT:PCBM), under illumination of AM 1.5 (100 mW/cm(2)). The higher
      PCE for TDPP-BBT-based polymer solar cells has been attributed to the low band
      gap of this copolymer as compared to PDPP-BBT, which increases the numbers of
      photogenerated excitons and corresponding photocurrent of the device. These
      results indicate that PDPP-BBT and TDPP-BBT act as excellent electron donors for
      bulk heterojunction devices.

PMID- 20158236
TI  - Hydroalkylation of alkynyl ethers via a gold(I)-catalyzed 1,5-hydride
      shift/cyclization sequence.
AB  - A series of alkynyl ethers react with an electrophilic gold(I) catalyst to
      produce a range of structurally complex spiro or fused dihydrofurans and
      dihydropyrans via a 1,5-hydride shift/cyclization sequence. This hydroalkylation
      process, which is performed under practical experimental conditions, can be
      applied to terminal as well as ester-substituted alkynes. It allows the efficient
      conversion of secondary or tertiary sp(3) C-H bonds into new C-C bonds by the
      nucleophilic addition of a vinylgold species onto an oxonium intermediate. The
      stereoselectivity of the cycloisomerization process toward the formation of a new
      five- or six-membered cycle appears to be dependent on steric factors and the
      alkyne substitution pattern.

PMID- 20158237
TI  - Biosynthesis of spinosyn in Saccharopolyspora spinosa: synthesis of permethylated
      rhamnose and characterization of the functions of SpnH, SpnI, and SpnK.
AB  - Spinosyn A is a polyketide-derived macrolide produced by Saccharopolyspora
      spinosa and is an active ingredient in several commercial insecticides. It is
      glycosylated by a tri-O-methylated rhamnose at C-9 and a forosamine at C-17.
      Previous studies indicated that the rhamnose methyltransferases are encoded by
      the spnH, spnI, and spnK genes. To verify the functions of these
      methyltransferases and to study how they are coordinated to achieve the desired
      level of methylation of rhamnose, we studied the catalytic properties of the
      spnH, spnI, and spnK gene products and validated their roles in the
      permethylation process of spinosyn A. Our data reported herein firmly established
      that SpnH, SpnI, and SpnK are the respective rhamnose 4'-, 2'-, and 3'-O
      methyltransferase. Investigation of the order of the methylation events revealed
      that only one route catalyzed by SpnI, SpnK, and SpnH in sequence is productive
      for the permethylation of the rhamnose moiety. Moreover, the completion of
      rhamnose permethylation is likely achieved by the proper control of the
      expression levels of the methyltransferase genes involved. These results set the
      stage for future exploitation of the spinosyn biosynthetic pathway to produce
      targeted spinosyn derivatives and, perhaps, new analogues.

PMID- 20158238
TI  - Atmospheric carbon dioxide changes photochemical activity, soluble sugars and
      volatile levels in broccoli (Brassica oleracea var. italica).
AB  - Atmospheric carbon dioxide (CO(2)) concentration is an environmental factor
      currently undergoing dramatic changes. The objective of the present study was to
      determine the effect of doubling the ambient CO(2) concentration on plant
      photochemistry as measured by photochemical quenching coefficient (qP), soluble
      sugars and volatiles in broccoli. Elevated CO(2) concentration increased qP
      values in leaves by up to 100% and 89% in heads, while glucose and sucrose in
      leaves increased by about 60%. Furthermore, in broccoli heads elevated CO(2)
      concentration induced approximately a 2-fold increase in concentrations of three
      fatty acid-derived C(7) aldehydes ((E)-2-heptenal, (E,Z)-2,4-heptadienal, (E,E)
      2,4-heptadienal), two fatty acid-derived C(5) alcohols (1-penten-3-ol, (Z)-2
      pentenol), and two amino acid-derived nitriles (phenyl propanenitrile, 3-methyl
      butanenitrile). In contrast, concentrations of the sulfur-containing compound 2
      ethylthiophene and C(6) alcohol (E)-2-hexenol decreased. Finally, elevated CO(2)
      concentration increased soluble sugar concentrations due to enhanced
      photochemical activity in leaves and heads, which may account for the increased
      synthesis of volatiles.

PMID- 20158239
TI  - Botulinum neurotoxin A protease: discovery of natural product exosite inhibitors.
AB  - A new mechanistic class of BoNT/A zinc metalloprotease inhibitors, from
      Echinacea, exemplified by the natural product d-chicoric acid (I1) is disclosed.
      A detailed evaluation of chicoric acid's mechanism of inhibition reveals that the
      inhibitor binds to an exosite, displays noncompetitive partial inhibition, and is
      synergistic with a competitive active site inhibitor when used in combination.
      Other components found in Echinacea, I3 and I4, were also inhibitors of the
      protease.

PMID- 20158240
TI  - Polybioside, a neuroactive compound from the venom of the social wasp Polybia
      paulista.
AB  - Polybioside (1) was isolated from the venom of the social wasp Polybia paulista,
      and its structure was assigned as 3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H
      pyran-2-yl 3-(1H-imidazol-4-yl)propanimidate by NMR and MS protocols. The
      application of polybioside in rat brain, followed by the detection of c-Fos
      protein expression in some brain regions, indicated the compound is neuroactive
      in a number of brain areas. Polybioside causes convulsions in rats, even when
      peripherally applied.

PMID- 20158241
TI  - Multiple bistability and tristability with dual spin-state conversions in
      [Fe(dpp)2][Ni(mnt)2]2 x MeNO2.
AB  - The multicomponent system of [Fe(dpp)(2)][Ni(mnt)(2)](2).MeNO(2) (1; dpp = 2,6
      bis(pyrazol-1-yl)pyridine and mnt = maleonitriledithiolate) was prepared by the
      reaction of [Fe(dpp)(2)](BF(4))(2) with (Bu(4)N)[Ni(mnt)(2)] in MeNO(2). Variable
      temperature X-ray structural analyses, magnetic susceptibility, and heat capacity
      measurements confirmed that 1 undergoes multiple spin-state conversions in both
      the cationic and anionic components. The asymmetric unit in the crystal contains
      one [Fe(dpp)(2)](2+) cation, two [Ni(mnt)(2)](-) anions ([Ni1](-) and [Ni2](-)),
      and one solvent molecule. Magnetic susceptibility measurements revealed that a
      paramagnetic state in the high-temperature region (HT phase) was abruptly
      converted to a diamagnetic low-temperature (LT) phase below 180 K as the
      temperature was lowered from 270 K. As the temperature was raised from 125 to 270
      K, successive phase transitions occurred to the HT phase via intermediate phases
      (IM1, IM2, and IM3) at 175.5, 186.5, 194.0, and 244.0 K, respectively. In the HT
      phase [Fe(dpp)(2)](2+) is in the high-spin state, and each [Ni1](-) and [Ni2](-)
      moiety is arranged in monomeric form with an S = (1)/(2) spin ground state. In
      the LT phase [Fe(dpp)(2)](2+) is in the low-spin state and the nickel moieties
      are dimerized and diamagnetic. In the IM1 and IM2 phases the iron(II) sites are
      partially in the HS state and both [Ni](-) moieties are dimeric, as suggested by
      (57)Fe Mossbauer measurements. In the IM3 phase, [Fe(dpp)(2)](2+) is in the HS
      state and the anions exist in both their monomeric ([Ni1](-)) and dimeric ([Ni2](
      )) forms. Rapid thermal quenching from 300 to 5 K yielded a metastable HS phase,
      which relaxed to the LT phase via the IM1 phase as the temperature was raised to
      150 K. A partial light induced spin transition on the iron site was observed at 5
      K.

PMID- 20158242
TI  - Malyngolide dimer, a bioactive symmetric cyclodepside from the panamanian marine
      cyanobacterium Lyngbya majuscula.
AB  - Fractionation of the extract of the marine cyanobacterium Lyngbya majuscula
      collected from Panama led to the isolation of malyngolide dimer (1). The planar
      structure of 1 was determined using 1D and 2D NMR spectroscopy and HRESI-TOFMS.
      The absolute configuration was established by chemical degradation followed by
      chiral GC-MS analyses and comparisons with an authentic sample of malyngolide
      seco-acid (4). Compound 1 showed moderate in vitro antimalarial activity against
      chloroquine-resistant Plasmodium falciparum (W2) (IC(50) = 19 microM) but roughly
      equivalent toxicity against H-460 human lung cell lines. Furthermore, because the
      closely related cyanobacterial natural product tanikolide dimer (5) was a potent
      SIRT2 inhibitor, compound 1 was evaluated in this assay but found to be
      essentially inactive.

PMID- 20158245
TI  - Homoisoflavonoids from the fibrous roots of Polygonatum odoratum with glucose
      uptake-stimulatory activity in 3T3-L1 adipocytes.
AB  - The EtOAc-soluble fraction of a 90% MeOH extract of the fibrous roots of
      Polygonatum odoratum was found to potentiate insulin-stimulated glucose uptake in
      differentiated 3T3-L1 adipocytes. Bioassay-guided fractionation yielded nine
      homoisoflavonoids (1-9), four of which were new (1-4), together with an
      isoflavone glycoside (10) and a flavanone glycoside (11). The structures of new
      compounds were elucidated on the basis of extensive 1D and 2D NMR spectroscopy,
      and the absolute configurations were deduced by CD spectra. All 11 compounds
      showed effects of sensitizing adipocytes for insulin in a cell-based glucose
      uptake assay using 3T3-L1 adipocytes. The results indicate that homoisoflavonoids
      may be potential insulin sensitizers.

PMID- 20158243
TI  - Gymnochromes E and F, cytotoxic phenanthroperylenequinones from a deep-water
      crinoid, Holopus rangii.
AB  - Bioactivity-guided fractionation of metabolites from the crinoid Holopus rangii
      led to the discovery of two new phenanthroperylenequinone derivatives,
      gymnochromes E (1) and F (2). Gymnochrome E showed cytotoxic activity toward the
      NCI/ADR-Res with an IC(50) of 3.5 microM. It also inhibited histone deacetylase-1
      with an IC(50) of 3.3 microM. Gymnochrome F was a moderate inhibitor of myeloid
      cell leukemia sequence 1 (MCL-1) binding to Bak. Two anthraquinone metabolites,
      emodic acid (4) and its new bromo derivative (5), were also isolated from the
      crinoid and show remarkable similarity to the phenanthroperylenequinone core,
      suggesting that these metabolites share the same polyketide biosynthetic pathway.

PMID- 20158246
TI  - Zeolite thin films: from computer chips to space stations.
AB  - Zeolites are a class of crystalline oxides that have uniform and molecular-sized
      pores (3-12 A in diameter). Although natural zeolites were first discovered in
      1756, significant commercial development did not begin until the 1950s when
      synthetic zeolites with high purity and controlled chemical composition became
      available. Since then, major commercial applications of zeolites have been
      limited to catalysis, adsorption, and ion exchange, all using zeolites in powder
      form. Although researchers have widely investigated zeolite thin films within the
      last 15 years, most of these studies were motivated by the potential application
      of these materials as separation membranes and membrane reactors. In the last
      decade, we have recognized and demonstrated that zeolite thin films can have new,
      diverse, and economically significant applications that others had not previously
      considered. In this Account, we highlight our work on the development of zeolite
      thin films as low-dielectric constant (low-k) insulators for future generation
      computer chips, environmentally benign corrosion-resistant coatings for aerospace
      alloys, and hydrophilic and microbiocidal coatings for gravity-independent water
      separation in space stations. Although these three applications might not seem
      directly related, they all rely on the ability to fine-tune important macroscopic
      properties of zeolites by changing their ratio of silicon to aluminum. For
      example, pure-silica zeolites (PSZs, Si/Al = infinity) are hydrophobic, acid
      stable, and have no ion exchange capacity, while low-silica zeolites (LSZs, Si/Al
      < 2) are hydrophilic, acid soluble, and have a high ion exchange capacity. These
      new thin films also take advantage of some unique properties of zeolites that
      have not been exploited before, such as a higher elastic modulus, hardness, and
      heat conductivity than those of amorphous porous silicas, and microbiocidal
      capabilities derived from their ion exchange capacities. Finally, we briefly
      discuss our more recent work on polycrystalline zeolite thin films as promising
      biocompatible coatings and environmentally benign wear-resistant and antifouling
      coatings. When zeolites are incorporated into polymer thin films in the form of
      nanocrystals, we also show that the resultant composite membranes can
      significantly improve the performance of reverse osmosis membranes for sea water
      desalination and proton exchange membrane fuel cells. These diverse applications
      of zeolites have the potential to initiate new industries while revolutionizing
      existing ones with a potential economic impact that could extend into the
      hundreds of billions of dollars. We have licensed several of these inventions to
      companies with millions of dollars invested in their commercial development. We
      expect that other related technologies will be licensed in the near future.

PMID- 20158247
TI  - Study of on-resin convergent synthesis of N-linked glycopeptides containing a
      large high mannose N-linked oligosaccharide.
AB  - Here we present a convergent on-resin glycosylamine coupling strategy for solid
      phase N-linked glycopeptide synthesis, and apply it to the synthesis of high
      mannose containing glycopeptides. In this strategy, the 2-phenylisopropyl
      protecting group is used as an orthogonal handle to create glycosylation sites on
      resin after synthesis of nonglycosylated peptides. In addition to allowing
      selective deprotection of aspartic acid residues for creation of glycosylation
      sites, the 2-phenylisopropyl protecting group also efficiently suppresses
      aspartimide formation during peptide synthesis. The key step of on-resin
      glycosylamine coupling to an aspartic acid residue was first optimized for a
      small sugar, N-acetylglucosamine, and then applied to a much larger high mannose
      oligosaccharide, Man(8)GlcNAc(2). Satisfying coupling yields were obtained for
      both small and large sugars. The use of on-resin glycosylamine coupling
      simplifies purification of N-linked glycopeptides, and also allows convenient
      recovery of unreacted valuable large oligosaccharides. This approach was applied
      to the solid phase synthesis of glycosylated forms of the 34 amino acid HIV-1
      gp41 C34 glycopeptide, which is an HIV-1 entry inhibitor. The HIV-1 entry
      inhibition assay of synthesized glycopeptides showed the retention of bioactivity
      of high mannose Man(8)GlcNAc(2)-C34.

PMID- 20158248
TI  - Molecular jigsaw: pattern diversity encoded by elementary geometrical features.
AB  - Scanning tunneling microscopy (STM) images of self-organized monolayers of
      Frechet dendrons display a variety of two-dimensional ordering motifs, which are
      influenced by engineering the molecular interactions. An interaction-site model
      condenses the essential molecular properties determined by molecular mechanics
      modeling, which in a Monte Carlo approach successfully predicts the various
      ordering motifs. This confirms that geometry as well as a few salient weak
      interaction sites encode these structural motifs.

PMID- 20158249
TI  - Fluorescent structural DNA nanoballs functionalized with phosphate-linked
      nucleotide triphosphates.
AB  - Highly labeled DNA nanoballs functionalized with phosphate-linked nucleotide
      triphosphates (dNTPs) were developed as a source of dNTPs for DNA polymerase. The
      particles were prepared by strand-displacement polymerization from a self
      complementary circular template. Imaged by atomic force microscopy, these
      functionalized particles appear as condensed fuzzy balls with diameters between
      50 and 150 nm. They emit a bright fluorescent signal, detected in 2 ms exposures
      with a signal-to-noise ratio of 25 when imaged using a TIR fluorescence
      microscope.

PMID- 20158250
TI  - Biomimetic branched hollow fibers templated by self-assembled fibrous
      polyvinylpyrrolidone structures in aqueous solution.
AB  - Branched hollow fibers are common in nature, but to form artificial fibers with a
      similar branched hollow structure is still a challenge. We discovered that
      polyvinylpyrrolidone (PVP) could self-assemble into branched hollow fibers in an
      aqueous solution after aging the PVP solution for about two weeks. On the basis
      of this finding, we demonstrated two approaches by which the self-assembly of PVP
      into branched hollow fibers could be exploited to template the formation of
      branched hollow inorganic fibers. First, inorganic material such as silica with
      high affinity against the PVP could be deposited on the surface of the branched
      hollow PVP fibers to form branched hollow silica fibers. To extend the
      application of PVP self-assembly in templating the formation of hollow branched
      fibers, we then adopted a second approach where the PVP molecules bound to
      inorganic nanoparticles (using gold nanoparticles as a model) co-self-assemble
      with the free PVP molecules in an aqueous solution, resulting in the formation of
      the branched hollow fibers with the nanoparticles embedded in the PVP matrix
      constituting the walls of the fibers. Heating the resultant fibers above the
      glass transition temperature of PVP led to the formation of branched hollow gold
      fibers. Our work suggests that the self-assembly of the PVP molecules in the
      solution can serve as a general method for directing the formation of branched
      hollow inorganic fibers. The branched hollow fibers may find potential
      applications in microfluidics, artificial blood vessel generation, and tissue
      engineering.

PMID- 20158251
TI  - Synthesis of a molecular charm bracelet via click cyclization and olefin
      metathesis clipping.
AB  - We describe the synthesis of a polycatenated cyclic polymer, a structure that
      resembles a molecular charm bracelet. Ruthenium-catalyzed ring-opening metathesis
      polymerization of an amino-containing cyclic olefin monomer in the presence of a
      chain transfer agent generated an alpha,omega-diazide functionalized polyamine.
      Cyclization of the resulting linear polyamine using pseudo-high-dilution copper
      catalyzed click cyclization produced a cyclic polymer in 19% yield. The click
      reaction was then further employed to remove linear contaminants from the cyclic
      polymer using azide- and alkyne-functionalized scavenging resins, and the
      purified cyclic polymer product was characterized by gel permeation
      chromatography, (1)H NMR spectroscopy, and IR spectroscopy. Polymer hydrogenation
      and conversion to the corresponding polyammonium species enabled coordination and
      interlocking of diolefin polyether fragments around the cyclic polymer backbone
      using ruthenium-catalyzed ring-closing olefin metathesis to afford a molecular
      charm bracelet structure. This charm bracelet complex was characterized by (1)H
      NMR spectroscopy, and the catenated nature of the small rings was confirmed using
      two-dimensional diffusion-ordered NMR spectroscopy.

PMID- 20158252
TI  - Chemzymes: a new class of structurally rigid tricyclic amphibian organocatalyst
      inspired by natural product.
AB  - A new class of structurally rigid tricyclic amphibian chiral catalyst was
      rationally designed based on the hexahydropyrrolo[2,3-b]indole skeleton as a new
      type of chemzyme. This new type of chemzyme possesses a structurally rigid
      tricyclic skeleton and a chiral pocket which provides a well-organized chiral
      environment for asymmetric induction, as well as a hydrophobic pocket to enable
      organocatalytic reactions to proceed smoothly both in organic solvents and in
      water.

PMID- 20158253
TI  - Identification of hydroxyl protons, determination of their exchange dynamics, and
      characterization of hydrogen bonding in a microcrystallin protein.
AB  - Heteronuclear correlation experiments employing perdeuterated proteins enable the
      observation of all hydroxyl protons in a microcrystalline protein by MAS solid
      state NMR. Dipolar-based sequences allow magnetization transfers that are >50
      times faster compared to scalar-coupling-based sequences, which significantly
      facilitates their assignment. Hydroxyl exchange rates were measured using EXSY
      type experiments. We find a biexponential decay behavior for those hydroxyl
      groups that are involved in side chain-side chain C-O-H...O horizontal lineC
      hydrogen bonds. The quantification of the distances between the hydroxyl proton
      and the carbon atoms in the hydrogen-bonding donor as well as acceptor group is
      achieved via a REDOR experiment. In combination with X-ray data and isotropic
      proton chemical shifts, availability of (1)H,(13)C distance information can aid
      in the quantitative description of the geometry of these hydrogen bonds.
      Similarly, correlations between backbone amide proton and carbonyl atoms are
      observed, which will be useful in the analysis of the registry of beta-strand
      arrangement in amyloid fibrils.

PMID- 20158254
TI  - Comparative studies on the chemical and cell-based antioxidant activities and
      antitumor cell proliferation properties of soy milk manufactured by conventional
      and commercial UHT methods.
AB  - The aims of this work were to compare antiproliferation, antioxidant activities
      and total phytochemicals and individual isoflavone profiles in soy milk processed
      by various methods including traditional stove cooking, direct steam injection,
      direct ultrahigh temperature (UHT), indirect UHT, and a two-stage simulated
      industry method, and a selected commercial soy milk product. Various processing
      methods significantly affected total saponin, phytic acid, and total phenolic
      content and individual isoflavone distribution. The laboratory UHT and the two
      stage processed soy milk exhibited relatively higher total phenolic content,
      total flavonoid content, saponin and phytic acid than those processed by the
      traditional and steam processed methods. Thermal processing caused obvious
      intertransformation but did not cause severe degradation except for breaking down
      of aglycons. Thermal processing significantly increased antioxidant capacities of
      soy milk determined by chemical analyses, but decreased cellular antioxidant
      capacities as compared to the raw soy milk. The raw and all processed soy milk
      exhibited antipoliferative activities against human HL-60 leukemia cells, AGS
      gastric tumor cells, and DU145 prostate cancer cells in a dose-dependent manner.
      The raw soy milk, but not the processed soy milk, exhibited a dose-dependent
      antiproliferative effect against colorectal adenocarcinoma Caco-2 cells. Taken
      together, these results indicate that various thermal processing methods change
      not only phytochemcials but also potential health-promoting effects of soy milk.

PMID- 20158255
TI  - Chemical assessment and in vitro antioxidant capacity of Ficus carica latex.
AB  - Ficus species possess latex-like material within their vasculatures, affording
      protection and self-healing from physical attacks. In this work, metabolite
      profiling was performed on Ficus carica latex. Volatiles profile was determined
      by HS-SPME/GC-IT-MS, with 34 compounds being identified, distributed by distinct
      chemical classes: 5 aldehydes, 7 alcohols, 1 ketone, 9 monoterpenes, 9
      sesquiterpenes and 3 other compounds. Sesquiterpenes constituted the most
      abundant class in latex (ca. 91% of total identified compounds). Organic acids
      composition was also characterized, by HPLC-UV, and oxalic, citric, malic,
      quinic, shikimic and fumaric acids were determined. Malic and shikimic acids were
      present in higher amounts (ca. 26%, each). The antioxidant potential of this
      material was checked by distinct in vitro chemical assays. A concentration
      dependent activity was noticed against DPPH, nitric oxide and superoxide
      radicals. Additionally, acetylcholinesterase inhibitory capacity was evaluated,
      but a weak effect was found.

PMID- 20158256
TI  - Enhancement of both salivary protein-enological tannin interactions and
      astringency perception by ethanol.
AB  - Red wine astringency has been associated with interactions of tannins with
      salivary proteins. Tannins are active protein precipitants. Not much evidence
      exists demonstrating contribution of other wine components to astringency. We
      aimed to investigate an eventual role of ethanol both in astringency and salivary
      protein-enological tannin interactions. A trained sensory panel scored perceived
      astringency. Salivary protein-tannin interactions were assessed by observing both
      tannin-dependent changes in salivary protein diffusion on cellulose membranes and
      tannin-induced salivary protein precipitation. Proanthocyanidins and gallotannins
      in aqueous and hydroalcoholic solutions were assayed. A biphasic mode of
      diffusion on cellulose membranes displayed by salivary proteins was unaffected
      after dilution with water or enological concentrations of ethanol. At those
      concentrations ethanol was not astringent. In aqueous solution, tannins provoked
      both restriction of salivary protein diffusion, protein precipitation, and
      astringency. Those effects were exacerbated by 13% ethanol. In summary,
      enological concentrations of ethanol exacerbate astringency and salivary protein
      tannin interactions.

PMID- 20158257
TI  - Tocotrienol distribution in foods: estimation of daily tocotrienol intake of
      Japanese population.
AB  - Tocotrienol (T3) is an unsaturated form of natural vitamin E that has been
      focused on because of its potential health benefits (i.e., antioxidative,
      antihypercholesterolemic, and antiangiogenic effects). The presence of T3 in some
      plant sources (e.g., rice bran and palm oil) is known, but its distribution in
      other edible sources and its daily intake remain unclear. In this study, we aimed
      at clarifying the distribution of T3 in various food sources and estimating the
      daily T3 intake of Japanese population. T3 contents of 242 food items and 64 meal
      items were measured by using normal-phase HPLC with fluorescence detection. As
      for the results, T3 contents were nondetectable to 12 mg T3/kg wet wt of food
      items, and nondetectable to 1.3 mg T3/item of processed (cooked) meal.
      Accordingly, the daily intake of T3 was estimated as 1.9-2.1 mg T3/day/person.
      The estimated daily intake of T3 appears rather low compared with the intake of
      tocopherol (8-10 mg/day/person as reported in the Japanese National Nutrition
      Survey), and additional T3 is important for its therapeutic aspects.

PMID- 20158258
TI  - Self-assembly of (S)-glutamic acid on Ag(100): a combined LT-STM and ab initio
      investigation.
AB  - Self-assembly of organic molecules at metal surfaces is of greatest importance in
      nanoscience; in fact, it opens new perspectives in the field of molecular
      electronics and in the study of biocompatible materials. Combining an
      experimental low-temperature scanning tunneling microscopy investigation with ab
      initio calculations, we succeeded to describe in detail (S)-glutamic acid
      adsorption on Ag(100) at T = 350 K. We find that (S)-glutamic acid organizes in a
      squared structure and, at variance with the majority of cases reported in
      literature, it adsorbs in the neutral form, 4.6 A above the surface plane. The
      interaction with the poorly reactive Ag substrate is only due to weak van der
      Waals forces, while H-bonds between carboxyl groups and the formation of a OCOH
      OCOH-OCOH-OCOH cycle at the vertex of the squares are the main responsible for
      the self-assembly.

PMID- 20158260
TI  - Fabrication of aligned magnetic nanoparticles using tobamoviruses.
AB  - We used genetically modified tube-shaped tobamoviruses to produce 3 nm aligned
      magnetic nanoparticles. Amino acid residues facing the central channel of the
      virus were modified to increase the number of nucleation sites. Energy dispersive
      X-ray spectroscopy and superconducting quantum interference device analysis
      suggest that the particles consisted of Co-Pt alloy. The use of tobamovirus
      mutants is a promising approach to making a variety of components that can be
      applied to fabricate nanometer-scaled electronic devices.

PMID- 20158261
TI  - Synthesis of phase transferable graphene sheets using ionic liquid polymers.
AB  - A practical route to the production of solution phase transferable graphene
      sheets using ionic liquid polymers (PIL) as a transferring medium is developed.
      Chemically converted graphene sheets decorated with PIL were found to be stable
      against the chemical reduction and well dispersed in the aqueous phase without
      any agglomeration. Upon the anion exchange of the PIL on graphene sheets, these
      PIL-modified graphene sheets in aqueous phase are readily transferred into the
      organic phase by changing their properties from hydrophilic to hydrophobic.

PMID- 20158262
TI  - Novel bi-nuclear boron complex with pyrene ligand: red-light emitting as well as
      electron transporting material in organic light-emitting diodes.
AB  - A novel boron complex bearing a pyrene ligand (CPB) was synthesized and
      introduced as the first example of a binuclear boron complex in organic light
      emitting diodes. In the solid state, CPB2 exhibited strong red emission. In the
      devices, red emission with Commission International de L'Eclairage (CIE)
      coordinates of (0.57, 0.42) was obtained by tuning the weight concentration of
      CPB2. CPB2 behaved as both an emitting and electron transporting material.

PMID- 20158263
TI  - Biomimetic syntheses of the neurotrophic natural products caryolanemagnolol and
      clovanemagnolol.
AB  - Separate short and modular syntheses of the isomeric natural products
      caryolanemagnolol and clovanemagnolol have been achieved starting from
      commercially available (-)-caryophyllene. The postulated biosynthetic pathways
      guided the syntheses of the neuroregenerative small molecules allowing their
      assembly in as few as two steps.

PMID- 20158264
TI  - Intermolecular aerobic oxidative allylic amination of simple alkenes with
      diarylamines catalyzed by the Pd(OCOCF3)2/NPMoV/O2 system.
AB  - Intermolecular aerobic oxidative allylic amination of simple alkyl alkenes with
      simple amines such as diphenylamine was induced by a Pd(OCOCF(3))(2)/NPMoV
      catalytic system, leading to the corresponding (E)-allylamines in good yield and
      selectivity through the formation of (eta(3)-allyl)palladium(II) trifluoroacetate
      species as a possible key intermediate.

PMID- 20158265
TI  - Active-site dynamics and large-scale domain motions of sulfite oxidase: a
      molecular dynamics study.
AB  - The physiologically vital enzyme sulfite oxidase employs rapid intramolecular
      electron transfer between a molybdenum ion in the C-terminal domain (the site of
      sulfite oxidation) and a heme moeity in the N-terminal domain to complete its
      catalytic cycle. Crystal structures of the enzyme show C- and N-terminal domain
      orientations that are not consistent with rapid intramolecular electron transfer.
      Domain motion has been postulated to explain this discrepancy. In the present
      work we employ molecular dynamics simulations to understand the large-scale
      domain motions of the enzyme. We observe motion of the N-terminal domain into an
      orientation similar to that postulated for rapid electron transfer. Our
      simulations also probe the dynamics of the active site and surrounding residues,
      adding a further level of structural and thermodynamic detail in understanding
      sulfite oxidase function.

PMID- 20158266
TI  - A fragment-based approach to identifying ligands for riboswitches.
AB  - Riboswitches are regions of mRNA that directly bind metabolites, leading to
      alteration of gene expression. We have developed fragment-based methods to screen
      for compounds that bind the Escherichia coli thiM riboswitch. Using complementary
      biophysical techniques we have identified several ligands with K(D) <100 microM.
      From these there is the potential to develop potent and selective modulators of
      riboswitch function.

PMID- 20158267
TI  - A fluorescent, reagentless biosensor for ADP based on tetramethylrhodamine
      labeled ParM.
AB  - Fluorescence assays for ADP detection are of considerable current interest, both
      in basic research and in drug discovery, as they provide a generic method for
      measuring the activity of ATPases and kinases. The development of a novel
      fluorescent biosensor is described that is based on a tetramethylrhodamine
      labeled, bacterial actin homologue, ParM. The design of the biosensor takes
      advantage of the large conformational change of ParM on ADP binding and the
      strong quenching of the tetramethylrhodamine fluorescence by stacking of the dye.
      ParM was labeled with two tetramethylrhodamines in close proximity, whereby the
      fluorophores are able to interact with each other. ADP binding alters the
      distance and relative orientation of the tetramethylrhodamines, which leads to a
      change in this stacking interaction and so in the fluorescence intensity. The
      final ADP biosensor shows approximately 15-fold fluorescence increase in response
      to ADP binding. It has relatively weak affinity for ADP (K(d) = 30 microM),
      enabling it to be used at substoichiometric concentrations relative to ADP, while
      reporting ADP concentration changes in a wide range around the K(d) value,
      namely, submicromolar to tens of micromolar. The biosensor strongly discriminates
      against ATP (>100-fold), allowing ADP detection against a background of
      millimolar ATP. At 20 degrees C, the labeled ParM binds ADP with a rate constant
      of 9.5 x 10(4) M(-1) s(-1) and the complex dissociates at 2.9 s(-1). Thus, the
      biosensor is suitable for real-time measurements, and its performance in such
      assays is demonstrated using a sugar kinase and a mammalian protein kinase.

PMID- 20158268
TI  - Subcellular quantitative proteomics reveals multiple pathway cross-talk that
      coordinates specific signaling and transcriptional regulation for the early host
      response to LPS.
AB  - Toll-like receptor 4 (TLR4) specifically recognizes lipopolysaccharide (LPS) to
      initiate signal transduction events that modulate host inflammatory responses.
      Although increasing numbers of genes have been characterized individually for
      their involvement in TLR4 signaling, the LPS-induced TLR4-mediated signaling
      pathway and connected networks are incompletely delineated. Given that most
      components of signaling pathways are activated at an early phase of the LPS
      induced response, we have employed a subcellular, SILAC-based quantitative
      proteomics approach to identify proteins in LPS-stimulated macrophages showing
      either cytosolic- or nuclear-specific changes in abundance. Subcellular
      fractionation not only reduces the spectral complexity for identifying maximum
      numbers of proteins but also enriches for low-abundance proteins within the
      compartment in which they function. Following 10 min LPS stimulation, the
      abundances of 508 proteins were found elevated in the cytosol, while the elevated
      levels of 678 proteins together with the decreased abundances of another 80
      proteins were quantified in nuclei. Coincident with observations that many key
      proteins involved in signal relays in the MAPK and NF-kappaB cascades were found
      simultaneously regulated in the cytosol, various transcriptional factors (TFs)
      such as IRFs were found activated in the nuclei. We also extended links between
      these intracellular pathways and various biological processes by identifying
      multiple pathway modules. For the first time, our combined data sets from
      quantitative proteomics and bioinformatics analyses provide a direct, system-wide
      insight into how cross-talk between upstream signaling pathways modulates the
      activities of particular TFs for regulating sets of pro-inflammatory genes.

PMID- 20158269
TI  - Structural basis for the superior activity of the large isoform of snow flea
      antifreeze protein.
AB  - The snow flea (Hypogastrum harveyi) is protected from freezing at sub-zero
      temperatures by a glycine-rich antifreeze protein (AFP) that binds to seed ice
      crystals and prevents them from growing larger. This AFP is hyperactive and
      comprises two isoforms [Graham, L. A., and Davies, P. L. (2005) Science 310,
      461]. The larger isoform (15.7 kDa) exhibits several-fold higher activity than
      the smaller isoform (6.5 kDa), although it is considerably less abundant. To
      establish the molecular basis for this difference in activity, we determined the
      sequence of the large isoform. The primary sequences of these two isoforms are
      surprisingly divergent. However, both contain tripeptide repeats and turn motifs
      that enabled us to build a three-dimensional model of the large isoform based
      upon the six-polyproline helix structure of the small isoform. Our model contains
      13 polyproline type II helices connected by proline-containing loops stacked into
      two flat sheets oriented antiparallel to one another. The structure is strictly
      amphipathic, with a hydrophilic surface on one side and a hydrophobic, putative
      ice-binding surface on the other. The putative ice-binding site is approximately
      twice as large in area as that of the small isoform, providing an explanation for
      the difference in activity that is consistent with other examples noted. By
      tagging the recombinant AFP with green fluorescent protein, we observed its
      binding to multiple planes of ice, especially the basal plane. This finding
      supports the correlation between AFP hyperactivity and basal plane binding first
      observed with spruce budworm AFP.

PMID- 20158270
TI  - Analysis of detergent-insoluble and whole cell lysate fractions of resting
      neutrophils using high-resolution mass spectrometry.
AB  - Neutrophilic granulocytes play a major role in the initiation and resolution of
      the inflammatory response, and demonstrate significant transcriptional and
      translational activity. Although much was known about neutrophils prior to the
      introduction of proteomics, the use of MS-based methodologies has provided an
      unprecedented tool to confirm and extend previous findings. In the present study,
      we performed a Gel-LC-MS/MS analysis of neutrophil detergent insoluble and whole
      cell lysate fractions of resting neutrophils. We achieved a set of
      identifications through the use of high-resolution mass spectrometry and
      validation of its data. We identified a total of 1249 proteins with a wide range
      of intensities from both detergent-insoluble and whole cell lysate fractions,
      allowing a mapping of proteins such as those involved in intracellular transport
      (Rab and Sec family proteins) and cell signaling (S100 proteins). These results
      represent the most comprehensive proteomic characterization of resting human
      neutrophils to date, and provide important information relevant for further
      studies of the immune system in health and disease. The methods applied here can
      be employed to help us understand how neutrophils respond to various physiologic
      and pathophysiologic conditions and could be extended to protein quantitation
      after cell activation.

PMID- 20158271
TI  - Identification of a novel family of snake venom proteins Veficolins from Cerberus
      rynchops using a venom gland transcriptomics and proteomics approach.
AB  - Cerberus rynchops (dog-faced water snake) belongs to Homalopsidae of Colubroidea
      (rear-fanged snakes). So far, venom compositions of snakes of the Homalopsidae
      family are not known. To determine the venom composition of C. rynchops, we have
      used both transcriptomics and proteomics approaches. The venom gland
      transcriptome revealed 104 ESTs and the presence of three known snake protein
      families, namely, metalloprotease, CRISP, and C-type lectin. In addition, we
      identified two proteins that showed sequence homology to ficolin, a mammalian
      protein with collagen-like and fibrinogen-like domains. We named them as ryncolin
      1 and ryncolin 2 (rynchops ficolin) and this new family of snake venom proteins
      as veficolins (venom ficolins). On the basis of its structural similarity to
      ficolin, we speculate that ryncolins may induce platelet aggregation and/or
      initiate complement activation. To determine the proteome, the whole C. rynchops
      venom was trypsinized and fractionated by reverse phase HPLC followed by MALDI
      MS/MS analysis of the tryptic peptides. Analysis of the tandem mass spectrometric
      data indicated the presence of all protein families compared to the translated
      cDNA library. Overall, our combined approach of transcriptomics and proteomics
      revealed that C. rynchops venom is among the least complex snake venom
      characterized to date despite the presence of a new family of snake venom
      proteins.

PMID- 20158272
TI  - Ligand-protein cross-docking with water molecules.
AB  - The accuracy of ligand-protein docking may be affected by the presence of water
      molecules on the surface of the protein. Cross-docking simulations have been
      performed on a number of ligand-protein complexes for various proteins whose
      crystal structures contain water molecules in their binding sites. Only common
      sets of water molecules found in the binding site of the proteins were
      considered. A statistically significant overall increase in accuracy was observed
      when water molecules were included in cross-docking simulations. These results
      confirm the importance of including water molecules whenever possible in ligand
      protein docking simulations.

PMID- 20158273
TI  - Novel biomarkers of 3-chloro-1,2-propanediol exposure by ultra performance liquid
      chromatography/mass spectrometry based metabonomic analysis of rat urine.
AB  - To select early, sensitive biomarkers of 3-chloro-1,2-propanediol (3-MCPD)
      exposure, a single dose of 30 mg/kg/day 3-MCPD was administered to male Wistar
      rats for 40 days. Significant elevations of serum creatinine and blood urea
      nitrogen concentrations were observed on day 40, and urine N-acetyl-beta-D
      glucosaminidase and beta-galactosidase (beta-Gal) activities were observed on day
      20. Slight renal tubule hydropic degeneration and spermatozoa decreases were
      observed on day 10. The endogenous metabolite profile of rat urine was
      investigated by ultra performance liquid chromatography/mass spectrometry with
      electrospray ionization (ESI). Principal component analysis and partial least
      squares enabled clusters to be visualized, with a trend of clustering on day 10
      in ESI- and the greatest differences on days 30 and 40. Galactosylglycerol, a
      marker contributing to the clusters, which had earlier variations than
      conventional biomarkers and the most significant elevations as compared to other
      novel biomarkers, was first considered to be an early, sensitive biomarker in
      evaluating the effect of 3-MCPD exposure. The identification of
      galactosylglycerol was carried out by beta-Gal catalysis, and the possible
      mechanism of urine galactosylglycerol variation was elucidated.

PMID- 20158275
TI  - Surface-energy engineering of graphene.
AB  - Contact angle goniometry is conducted for epitaxial graphene on SiC. Although
      only a single layer of epitaxial graphene exists on SiC, the contact angle
      drastically changes from 69 degrees on SiC substrates to 92 degrees on graphene.
      It is found that there is no thickness dependence of the contact angle from the
      measurements of single-, bi-, and multilayer graphene and highly ordered
      pyrolytic graphite (HOPG). After graphene is treated with oxygen plasma, the
      level of damage is investigated by Raman spectroscopy and the correlation between
      the level of disorder and wettability is reported. By using a low-power oxygen
      plasma treatment, the wettability of graphene is improved without additional
      damage, which can solve the adhesion issues involved in the fabrication of
      graphene devices.

PMID- 20158274
TI  - A new photoproduct of 5-methylcytosine and adenine characterized by high
      performance liquid chromatography and mass spectrometry.
AB  - The UV portion of sunlight is mutagenic and can modify DNA by producing various
      photoproducts. UV photodamage often occurs at dipyrimidine sites, to give
      cyclobutane, pyrimidine-(6-4)-pyrimidone (6-4), and pyrimidine-(6-4)-Dewar
      pyrimidone (Dewar) photoproducts, and at TA and AA sites. There is no reported
      evidence, however, of UV photoproduct formation between C or 5-methylC ((m)C) and
      A. Irradiation of d(GTAT(m)CATGAGGTGC) with UVB light at physiological pH gives
      an unexpected photoproduct that undergoes fast thermal deamination but does not
      revert to its original structure under UVC irradiation. Evidence from nuclease P1
      digestion coupled with electrospray ionization (ESI)-MS/MS is in accord with
      product formation between (m)C and A. HPLC analysis indicates that deamination
      gives a T<>A photoproduct that coelutes on reverse-phase chromatography with the
      well-known TA* photoproduct, formed from an initial [2 + 2] reaction between C5
      C6 and C6-C5 of the adjacent thymine and adenine [as shown by Zhao , X. , et al.
      ( 1996 ) Nucleic Acids Res. 24 , 1554 - 1560 and Davies , R. J. , et al. ( 2007 )
      Nucleic Acids Res. 35 , 1048 - 1053 ]. Furthermore, the deamination product of
      the unknown (m)C<>A photoproduct and the TA* photoproduct undergo nearly
      identical fragmentation in tandem MS. The evidence, taken together, indicates
      that the deamination product of the unknown (m)CA photoproduct has the same
      chemical structure as the TA* photoproduct. Therefore, the unknown photoproduct
      is referred to as the (m)CA* photoproduct, which, upon deamination, gives the TA*
      photoproduct.

PMID- 20158276
TI  - Biostructure-like surfaces with thermally responsive wettability prepared by
      temperature-induced phase separation micromolding.
AB  - We present a very efficient and convenient approach to obtain smart biosurfaces
      by directly replicating biological surface structures. It is realized by a two
      step replication process combining regular replica molding and temperature
      induced phase separation micromolding (PSmicroM). The negative replicas of
      biological surface structures using poly(dimethylsiloxane) as the replication
      material are durable molds for further replication. The positive replicas of
      biological surface structures are obtained by the second step replication using
      PSmicroM of poly(N-isopropylacrylamide) aqueous solution, which can be easily
      carried out just by adjusting temperature. With cold water as good solvent and
      hot water as nonsolvent, an environmentally friendly PSmicroM process is
      successfully achieved, and organic solvents for PSmicroM are completely avoided.
      Our study has demonstrated that the micro- and nanostructures of the lotus leaf
      and rice leaf can be well replicated using this two-step replication process, and
      the replicated artificial lotus leaf and rice leaf using poly(N
      isopropylacrylamide) exhibit good thermally responsive wettability.

PMID- 20158277
TI  - Effect of specific anion on templated crystal nucleation at the liquid-liquid
      interface.
AB  - In this work, we have investigated the effect of potassium salts of different
      anions upon the crystal nucleation of K(2)SO(4) as interfacially templated by a
      surfactant monolayer of 1-octadecylamine (ODA), in an aqueous microdroplet system
      bounded by a liquid-liquid interface with 1-decanol. The salts used were
      K(2)HPO(4), KCl, KBr, KI, KNO(3), and KSCN, present at an initial concentration
      of 10 mM within an aqueous microdroplet containing K(2)SO(4) at an initial
      concentration of 287 mM. Supersaturation and subsequent crystallization were
      isothermally induced by droplet dissolution into the dehydrating decanol phase.
      The K(2)SO(4) solute crystallization behavior was studied by measurement of the
      calculated concentration of the solute in the microdroplet at the onset of
      crystallization, i.e., at the first perceptible microscopic appearance of a solid
      phase, and by crystal habit. Certain salts, e.g., K(2)HPO(4), had almost no
      influence on the templating ability of ODA, while the ability of ODA to template
      nucleation and direct the formation of regular crystal habit of K(2)SO(4) became
      appreciably disrupted in the presence of more chaotropic anions, such as SCN(-)
      or NO(3)(-). The propensity for anions to disrupt crystal templating was clearly
      seen to follow a Hofmeister trend. For crystallization events induced in the
      absence of ODA, however, these added salts had no influence on the outcome of the
      events. Microdroplets bounded by an ODA monolayer were also found to undergo
      droplet shrinkage into the surrounding dehydrating phase at a rate which
      generally depended upon the nature of the anion in the droplet, with chaotropic
      anions having an apparent effect of promoting shrinkage. Our findings suggest
      that the packing or ordering of an ODA monolayer at a liquid-liquid interface is
      strongly influenced by an interaction between anions in the aqueous phase and the
      surfactant monolayer at the liquid-liquid interface, which is manifested in its
      effect upon the crystal templating behavior. These intriguing results can have
      important implications for the understanding of biomineralization processes which
      occur in heterogeneous environments.

PMID- 20158279
TI  - Building conjugated organic structures on Si(111) surfaces via microwave-assisted
      Sonogashira coupling.
AB  - A novel step-by-step method employing microwave-assisted Sonogashira coupling is
      developed to grow fully conjugated organosilicon structures. As the first case
      study, p-(4-bromophenyl)acetylene is covalently conjugated to a p-(4
      iodophenyl)acetylene-derived monolayer on a Si(111) surface. By bridging the two
      aromatic rings with C[triple bond]C, the pregrown monolayer is structurally
      extended outward from the Si surface, forming a fully conjugated (p-(4
      bromophenylethynyl)phenyl)vinylene film. The film growth process, which reaches
      90% yield after 2 h, is characterized thoroughly at each step by using X-ray
      reflectivity (XRR), X-ray standing waves (XSW), and X-ray fluorescence (XRF). The
      high yield and short reaction time offered by microwave-assisted surface
      Sonogashira coupling chemistry make it a promising strategy for functionalizing
      Si surfaces.

PMID- 20158280
TI  - Electrochemical reaction of water-insoluble organic droplets in aqueous
      electrolytes using acoustic emulsification.
AB  - Electrochemical oxidation of water-insoluble amines (n-octylamine and n
      decylamine) was successfully accomplished in aqueous electrolytes using acoustic
      emulsification. Acoustically prepared emulsions of fumaric acid diethyl ester in
      aqueous electrolytes can be also electro-reduced very smoothly. Ultrasonication
      to the water-insoluble organic substrate/aqueous electrolyte mixtures allowed a
      formation of very stable emulsions having the characteristic of giving narrow
      monomer droplet size distributions in the submicrometer range in aqueous
      electrolytes without added surfactants, and the smooth electrochemical reaction
      in the emulsions took place via direct electron transfer between the electrode
      and the water-insoluble organic droplets. In this kind of electron-transfer
      system, supporting electrolyte should be dissolved not only in the aqueous phase
      but also in the organic droplets and should contribute to the formation of an
      electric bilayer inside the droplets.

PMID- 20158281
TI  - Surface modification and polysaccharide deposition on BisGMA/TEGDMA thermoset.
AB  - Bisphenol A glycidylmethacrylate (BisGMA)/triethyleneglycol dimethacrylate
      (TEGDMA) thermosets and composites are well-known examples of biomaterials for
      dental applications that are receiving growing interest for orthopedic
      applications. While mechanical bulk properties are guaranteed by the presence of
      reinforcing fibers, in vitro and in vivo performances of these materials are
      ultimately driven by their ability to establish proper interactions between their
      surface and the surrounding tissues. Hence, the development of novel chemical
      processes enabling the introduction of bioactive molecules on the surface of
      these methacrylate-based thermosets is of particular interest. In the present
      work, we have devised a chemical strategy to expose carboxylic groups on the
      surface of the BisGMA/TEGDMA thermoset. The presence of negative charges was
      confirmed by Fourier transform infrared-attenuated total reflectance and by UV
      vis spectrophotometry. Bulk mechanical properties and surface morphology of the
      thermoset were only slightly affected upon chemical functionalization. The
      activated material was further refined by the deposition of a lactose-modified
      chitosan (chitlac) driven by strong electrostatic interactions. The presence of
      the bioactive polysaccharide was confirmed by fluorescence spectroscopy and by
      confocal laser scanning microscopy measurements. Scratch tests were performed to
      evaluate the mechanical behavior of the coating. Finally, in vitro tests revealed
      that the presence of chitlac led to a slight enhancement of cell proliferation
      with respect to the unmodified BisGMA/TEGDMA thermoset. This effect was more
      pronounced when chitlac decorated with an arginine-glycine-aspartic acid (RGD)
      peptide was used in the preparation of the coating. In the latter case, the in
      vitro performance of the coated BisGMA/TEGDMA thermoset became comparable with
      that of clinically used roughened titanium.

PMID- 20158282
TI  - Visualization of the cellulose biosynthesis and cell integration into cellulose
      scaffolds.
AB  - By controlling the microarchitecture of bioengineered scaffolds for artificial
      tissues, their material and cell-interaction properties can be designed to mimic
      native correspondents. Current understanding of this relationship is sparse and
      based on microscopy requiring harsh sample preparation and labeling, leaving it
      open to which extent the natural morphology is studied. This work introduces
      multimodal nonlinear microscopy for label-free imaging of tissue scaffolds,
      exemplified by bacterial cellulose. Unique three-dimensional images visualizing
      the formation of nanofiber networks throughout the biosynthesis, revealing that
      supra-structures (layered structures, cavities) are formed. Cell integration in
      compact scaffolds was visualized and compared with porous scaffolds. While the
      former showed distinct boundaries to the native tissue, gradual cell integration
      was observed for the porous material. Thus, the degree of cell integration can be
      controlled through scaffold supra-structures. This illustrates the potential of
      nonlinear microscopy for noninvasive imaging of the intriguing interaction
      mechanisms between scaffolds and cells.

PMID- 20158283
TI  - Risk factors and drug interactions predisposing to statin-induced myopathy:
      implications for risk assessment, prevention and treatment.
AB  - HMG-CoA reductase inhibitors ('statins') represent the most effective and widely
      prescribed drugs currently available for the reduction of low-density lipoprotein
      cholesterol, a critical therapeutic target for primary and secondary prevention
      of cardiovascular atherosclerotic disease. In the face of the established lipid
      lowering and the emerging pleiotropic properties of statins, the patient
      population suitable for long-term statin treatment is expected to further expand.
      An overall positive safety and tolerability profile of statins has been
      established, although adverse events have been reported. Skeletal muscle-related
      events are the most common adverse events of statin treatment. Statin-induced
      myopathy can (rarely) manifest with severe and potentially fatal cases of
      rhabdomyolysis, thus rendering the identification of the underlying predisposing
      factors critical. The purpose of this review is to summarize the factors that
      increase the risk of statin-related myopathy. Data from published clinical
      trials, meta-analyses, postmarketing studies, spontaneous report systems and case
      reports for rare effects were reviewed. Briefly, the epidemiology, clinical
      spectrum and molecular mechanisms of statin-associated myopathy are discussed. We
      further analyse in detail the risk factors that precipitate or increase the
      likelihood of statin-related myopathy. Individual demographic features, genetic
      factors and co-morbidities that may account for the significant interindividual
      variability in the myopathic risk are presented. Physicochemical properties of
      statins have been implicated in the differential risk of currently marketed
      statins. Pharmacokinetic interactions with concomitant medications that interfere
      with statin metabolism and alter their systemic bioavailability are reviewed. Of
      particular clinical interest in cases of resistant dyslipidaemia is the
      interaction of statins with other classes of lipid-lowering agents; current data
      on the relative safety of available combinations are summarized. Finally, we
      provide an update of current guidelines for the prevention and management of
      statin myopathy. The identification of patients with an increased proclivity to
      statin-induced myopathy could allow more cost-effective approaches of monitoring
      and screening, facilitate targeted prevention of potential complications, and
      further improve the already overwhelmingly positive benefit-risk ratio of
      statins.

PMID- 20158285
TI  - Drug utilization of Intrinsa (testosterone patch) in England: interim analysis of
      a prescription-event monitoring study to support risk management.
AB  - BACKGROUND: Intrinsa is a transdermal testosterone patch that is indicated for
      use in hypoactive sexual desire disorder (HSDD) in women who have undergone
      bilateral oophorectomy and hysterectomy (surgically-induced menopause) receiving
      concomitant oestrogen therapy. OBJECTIVE: To describe the utilization
      characteristics of the patients prescribed testosterone patch (Intrinsa) based on
      an interim analysis of an ongoing Prescription-Event Monitoring study in England,
      and to assess, where possible, if the product is being used within the licensed
      therapeutic indication. METHODS: In this interim analysis, patients were
      identified from dispensed prescriptions that had been issued by general
      practitioners (GPs) for Intrinsa from March 2007. 'Green form' questionnaires
      were sent to GPs 6 months following the date of the first prescription for
      Intrinsa for each individual patient, requesting information including age, sex,
      start and stop dates of treatment (if stopped), prescribing indication and
      reasons for stopping. Additional questions were asked regarding the patient's
      menopausal status and use of concomitant oestrogen therapy. RESULTS: The interim
      cohort consisted of 756 patients. The majority of patients were reported to be
      female (746 [98.7%]) with a median (interquartile range) age of 50 years (44-55
      years). The most commonly reported indication was the licensed indication of HSDD
      in 580 patients (76.7%). Just under one-half of the patients (n = 364 [48.1%])
      were reported to have been hysterectomized and bilaterally oophorectomized
      (surgically-induced menopause) prior to starting Intrinsa; 127 patients (16.8%)
      were naturally menopausal. For 222 patients (29.4%) the GP specified that the
      patient was not using concomitant oestrogen therapy. Overall, only 219 patients
      (29.0%) in the cohort were being prescribed Intrinsa according to the
      manufacturer's recommendations. CONCLUSIONS: This study has highlighted that some
      clinicians are prescribing this product outside the recommended terms of the
      licence, with less than 30% of patients receiving Intrinsa according to
      prescribing guidelines. All events experienced by these patients will be analysed
      to detect any possible adverse events from using Intrinsa outside of the licensed
      therapeutic indication. The findings support the ongoing postmarketing risk
      management of the product.

PMID- 20158286
TI  - Prospective drug safety monitoring using the UK primary-care General Practice
      Research Database: theoretical framework, feasibility analysis and extrapolation
      to future scenarios.
AB  - BACKGROUND: Post-launch drug safety monitoring is essential for the detection of
      adverse drug signals that may be missed during preclinical trials. Traditional
      methods of postmarketing surveillance such as spontaneous reporting have
      intrinsic limitations, many of which can be overcome by the additional
      application of structured pharmacoepidemiological approaches. However, further
      improvement in drug safety monitoring requires a shift towards more proactive
      pharmacoepidemiological methods that can detect adverse drug signals as they
      occur in the population. OBJECTIVE: To assess the feasibility of using proactive
      monitoring of an electronic medical record system, in combination with an
      independent endpoint adjudication committee, to detect adverse events among users
      of selected drugs. METHODS: UK General Practice Research Database (GPRD)
      information was used to detect acute liver disorder associated with the use of
      amoxicillin/clavulanic acid (hepatotoxic) or low-dose aspirin (acetylsalicylic
      acid [non-hepatotoxic]). Individuals newly prescribed these drugs between 1
      October 2005 and 31 March 2006 were identified. Acute liver disorder cases were
      assessed using GPRD computer records in combination with case validation by an
      independent endpoint adjudication committee. Signal generation thresholds were
      based on the background rate of acute liver disorder in the general population.
      RESULTS: Over a 6-month period, 8148 patients newly prescribed
      amoxicillin/clavulanic acid and 5577 patients newly prescribed low-dose aspirin
      were identified. Within this cohort, searches identified 11 potential liver
      disorder cases from computerized records: six for amoxicillin/clavulanic acid and
      five for low-dose aspirin. The independent endpoint adjudication committee
      refined this to four potential acute liver disorder cases for whom paper-based
      information was requested for final case assessment. Final case assessments
      confirmed no cases of acute liver disorder. The time taken for this study was 18
      months (6 months for recruitment and 12 months for data management and case
      validation). To reach the estimated target exposure necessary to raise or rule
      out a signal of concern to public health, we determined that a recruitment period
      2-3 times longer than that used in this study would be required. Based on the
      real market uptake of six commonly used medicinal products launched between 2001
      and 2006 in the UK (budesonide/eformoterol [fixed-dose combination], duloxetine,
      ezetimibe, metformin/rosiglitazone [fixed-dose combination], tiotropium bromide
      and tadalafil) the target exposure would not have been reached until the fifth
      year of marketing using a single database. CONCLUSION: It is feasible to set up a
      system that actively monitors drug safety using a healthcare database and an
      independent endpoint adjudication committee. However, future successful
      implementation will require multiple databases to be queried so that larger study
      populations are included. This requires further development and harmonization of
      international healthcare databases.

PMID- 20158284
TI  - New insights in toxic epidermal necrolysis (Lyell's syndrome): clinical
      considerations, pathobiology and targeted treatments revisited.
AB  - Drug-induced toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is
      a life-threatening drug reaction characterized by extensive destruction of the
      epidermis and mucosal epithelia. The eyes are typically involved in TEN. At
      present, the disease has a high mortality rate. Conceptually, TEN and the Stevens
      Johnson syndrome are closely related, although their severity and outcome are
      different. Distinguishing TEN from severe forms of erythema multiforme relies on
      consideration of aetiological, clinical and histological characteristics. The
      current understanding of the pathomechanism of TEN suggests that keratinocytes
      are key initiator cells. It is probable that the combined deleterious effects on
      keratinocytes of both the cytokine tumour necrosis factor (TNF)-alpha and
      oxidative stress induce a combination of apoptotic and necrotic events. As yet,
      there is no evidence indicating the superiority of monotherapy with
      corticosteroids, ciclosporin (cyclosporine) or intravenous immunoglobulins over
      supportive care only for patients with TEN. However, the current theory of TEN
      pathogenesis supports the administration of a combination of
      antiapoptotic/antinecrotic drugs (e.g. anti-TNF-alpha antibodies plus N
      acetylcysteine) targeting different levels of the keratinocyte failure machinery.

PMID- 20158287
TI  - The relationship between study characteristics and the prevalence of medication
      related hospitalizations: a literature review and novel analysis.
AB  - BACKGROUND: Studies on medication-related hospitalizations differ in study
      setting, studied population, outcome, and method of data collection. Thus,
      extrapolations based on a meta-analysis of unselected studies may be biased.
      OBJECTIVE: To explore the influence of study characteristics on the prevalence of
      medication-related hospitalizations. METHODS: After a structured literature
      search, the retrieved studies were categorized based on the following aspects:
      (i) study setting (e.g. all hospital admissions vs only acute hospital
      admissions); (ii) study population (e.g. an entire hospital, study ward(s),
      selected population and/or age group); (iii) outcome of medication-related
      problem (e.g. adverse drug reaction [ADR] vs adverse drug event [ADE]); (iv)
      method of data collection (e.g. medical chart review, spontaneous reporting or
      database research); and (v) continent in which the study took place (only for
      studies looking at all acute admissions). We then examined the relationship
      between these factors and reported prevalence of medication-related hospital
      admissions. RESULTS: Ninety-five studies were analysed, with a range of reported
      prevalence of medication-related hospitalizations from 0.1% to 54%. Higher
      prevalences were found in the studies examining all hospital admissions than in
      the studies examining only acute hospital admissions. In addition, higher
      prevalences were found in the elderly population than in children. As would be
      expected, higher prevalences were also found in studies examining ADEs than in
      studies examining only ADRs. With respect to the method of data collection,
      medical chart screening resulted in higher prevalences of medication-related
      hospitalizations than database methods or spontaneous reporting. Combined studies
      in Europe show lower prevalences of medication-related hospital admissions than
      in other continents included in the study. DISCUSSION: The reported prevalence of
      medication-related hospital admissions varies as a function of the setting (all
      admissions or only acute admissions), studied population (entire hospital,
      specific wards, selected population and age group), outcome (ADR/ADE), the method
      of data collection and the continent in which the study is performed. CONCLUSION:
      Extrapolation using national hospital admission data and the prevalence
      identified by pooling international studies should be carried out with great
      caution.

PMID- 20158288
TI  - 'First, do no harm': factors that influence pharmacists making decisions about
      over-the-counter medication: a qualitative study in Northern Ireland.
AB  - BACKGROUND: Little is known about how community pharmacists make decisions about
      which over-the-counter (OTC) medication to supply to a patient and the role of
      clinical evidence in making those decisions. OBJECTIVE: To explore factors that
      influence product selection by the pharmacist and the role of evidence-based
      practice in this decision. METHODS: In this qualitative study, community
      pharmacists registered in Northern Ireland and recruited via advertising and
      various qualitative sampling techniques, participated in face-to-face, semi
      structured interviews (June 2007-September 2007) to discuss issues around OTC
      medication, including the use of evidence, how they judged a product to be
      effective, and their views on evidence-based medicine and its application to OTC
      medication. All interviews were digitally recorded, fully transcribed and
      analysed using the principles of constant comparison. RESULTS: Twenty-six
      pharmacists participated in interviews. Safety was the over-arching consideration
      for pharmacists when making decisions. The subordinate themes were product,
      patient and professional factors. In terms of the product subordinate theme, use
      or consideration of evidence was secondary in the selection of OTC medicines.
      Pharmacists considered the potential for harm in the first instance and if the
      product was deemed safe, although lacking any evidence for effectiveness, the
      product was supplied. In relation to patient factors, it emerged that pharmacists
      were influenced by patient demand for a particular OTC product and wanted to meet
      patient expectations, provided that the requested product was judged to be safe.
      Similarly, professional factors such as ethical considerations (primarily in
      relation to safety) and respecting patient choice also influenced decision
      making. However, pharmacists recognized the conflict between professional
      requirements to practise according to evidence-based principles and patient
      demands. CONCLUSION: This study suggests that pharmacists considered safety above
      all other factors when recommending OTC products to patients, and evidence of
      effectiveness was seldom considered when selling OTC medicines. If evidence-based
      practice is to influence this type of decision, pharmacists need to use the
      evidence that is available and be prepared to discuss evidence with patients.

PMID- 20158289
TI  - Medical management of Lennox-Gastaut syndrome.
AB  - Lennox-Gastaut syndrome occurs in 3% of children with epilepsy and is
      characterized by multiple seizure types, slow spike-and-wave discharges and a
      poor prognosis for seizure control and cognitive development. Although randomized
      controlled trials of adjunctive felbamate, lamotrigine, topiramate and rufinamide
      have demonstrated a > or =50% reduction in seizure frequency, very few children
      achieve complete seizure control and a Cochrane review of the treatment of Lennox
      Gastaut syndrome concluded that the optimum treatment was uncertain and that no
      drug has been shown to be highly efficacious. Valproate, lamotrigine and
      topiramate were considered recently by expert panels in the US and Europe to be
      the first-line drugs. The ketogenic diet may be more effective than antiepileptic
      drugs and should be considered early in treatment. An improvement in the
      management of Lennox-Gastaut syndrome requires a better understanding of the
      pathophysiology of this disorder and the development of animal models in which to
      test new compounds.

PMID- 20158290
TI  - Dose effects of triazolam and alcohol on cognitive performance in healthy
      volunteers.
AB  - Benzodiazepines and alcohol are widely used psychoactive substances that have
      performance-impairing effects. Research suggests that the impairment profiles for
      benzodiazepines and alcohol differ, although few cognitive psychopharmacological
      studies have directly compared these drugs. This double-blind, double-dummy,
      placebo-controlled, repeated measures study directly compared the acute dose
      effects of triazolam (0.125, 0.25 mg/70 kg) and alcohol (0.40, 0.80 g/kg) in 20
      social drinkers. At doses that produced comparable psychomotor impairment,
      triazolam was more likely to impair several objective measures of cognitive
      performance (e.g., episodic memory, divided attention) and to slow performance
      across several measures. However, only alcohol impaired accuracy on the digit
      symbol substitution and semantic memory tasks. In addition to objective measures,
      both drugs impaired awareness of performance impairments (i.e., metacognition)
      such that participants overestimated impairment, and the magnitude of this effect
      was generally larger for alcohol. Only triazolam impaired other measures of
      metacognition (e.g., error detection on a choice reaction time task). Future
      research might examine the clinical implications of the performance impairments
      reported here given the widespread use of benzodiazepines and alcohol.

PMID- 20158292
TI  - The relationship between in-treatment abstinence and post-treatment abstinence in
      a smoking cessation treatment.
AB  - Previous research has indicated that abstinence early in a smoking cessation
      program is predictive of successful posttreatment abstinence. However, it has not
      been established whether or not this effect is independent of other in-treatment
      abstinence patterns. In this paper the relationship between three potentially
      important aspects of in-treatment smoking abstinence and posttreatment smoking
      abstinence are examined: early abstinence, extended abstinence, and end-of
      treatment abstinence. We examined the relationship between smoking behavior
      measured each weekday over 70 visits (approximately 14 weeks) of a contingency
      management smoking cessation program and at a follow-up visit 6 months after
      study entry (3 months after the scheduled end of treatment). Ninety-five of 102
      participants were successfully followed-up. Seven of these 95 participants were
      confirmed abstinent. Early abstinence, defined as abstinence during the first 10
      treatment visits, was significantly and independently related to follow-up
      abstinence (OR = 56.67 [7.29-440.63]). Extended abstinence and end-of-treatment
      abstinence were related to follow-up abstinence, but not independent of early
      abstinence based on multiple regression models. Inclusion of a variety of
      demographic and environmental characteristics did not significantly alter this
      relationship. Thus, consistent with the previous literature, the establishment of
      early abstinence appears to be crucial to establishing longer-term abstinence,
      independent of other in-treatment abstinence patterns.

PMID- 20158291
TI  - Dose effects of triazolam and scopolamine on metamemory.
AB  - The present study compared the acute dose effects of the benzodiazepine triazolam
      and the anticholinergic scopolamine on metamemory (knowledge and awareness of
      one's own memory) in a two-phase paradigm designed to assess effects on both
      monitoring and control components of metamemory in both semantic (general
      knowledge) and episodic memory (cued-recall) tasks. Placebo and 2 doses each of
      triazolam (0.125, 0.25 mg/70 kg, oral) and scopolamine (0.25, 0.50 mg/70 kg,
      subcutaneous) were administered to 80 healthy volunteers (16 per group) in a
      double-blind, double-dummy, independent groups design. Both triazolam and
      scopolamine impaired episodic memory (quantity and accuracy) but not semantic
      memory. Results suggested that both drugs impaired monitoring as reflected in
      absolute accuracy measures (impaired calibration in the direction of
      overconfidence) and control sensitivity (the relationship between confidence and
      behavior). Overall, the results did not provide evidence for differences between
      triazolam and scopolamine in memory or metamemory. In addition to the clinical
      relevance of the observed effects, this study adds to the accumulating body of
      cognitive psychopharmacological research illustrating the usefulness of drug
      induced amnesia as a vehicle to explore memory and metamemory.

PMID- 20158293
TI  - A contingency-management intervention to promote initial smoking cessation among
      opioid-maintained patients.
AB  - Prevalence of cigarette smoking among opioid-maintained patients is more than
      threefold that of the general population and associated with increased morbidity
      and mortality. Relatively few studies have evaluated smoking interventions in
      this population. The purpose of the present study was to examine the efficacy of
      contingency management for promoting initial smoking abstinence. Forty methadone-
      or buprenorphine-maintained cigarette smokers were randomly assigned to a
      contingent (n = 20) or noncontingent (n = 20) experimental group and visited the
      clinic for 14 consecutive days. Contingent participants received vouchers based
      on breath carbon monoxide levels during Study Days 1 to 5 and urinary cotinine
      levels during Days 6 to 14. Voucher earnings began at $9.00 and increased by
      $1.50 with each subsequent negative sample for maximum possible of $362.50.
      Noncontingent participants earned vouchers independent of smoking status.
      Although not a primary focus, participants who were interested and medically
      eligible could also receive bupropion (Zyban). Contingent participants achieved
      significantly more initial smoking abstinence, as evidenced by a greater
      percentage of smoking-negative samples (55% vs. 17%) and longer duration of
      continuous abstinence (7.7 vs. 2.4 days) during the 2 week quit attempt than
      noncontingent participants, respectively. Bupropion did not significantly
      influence abstinence outcomes. Results from this randomized clinical trial
      support the efficacy of contingency management interventions in promoting initial
      smoking abstinence in this challenging population.

PMID- 20158294
TI  - Nicotine primes attention to competing affective stimuli in the context of
      salient alternatives.
AB  - Despite the importance of the subject, the effects of nicotine on the interplay
      between affect and attentional bias are not clear. This interplay was assessed
      with a novel design of the Primed Attentional Competition Task (PACT). It
      included a 200-ms duration emotional priming picture (negative, positive, or
      neutral) followed by a dual-target picture of two emotional faces side-by-side. A
      second task included an emotional priming picture followed by a single emotional
      target picture in a classic affective priming (CAP) task, assessing reaction time
      to identify the valence. Smokers completed the tasks in a double-blind repeated
      measures design wearing a nicotine patch on one day and a placebo patch on the
      other day. Consistent with hypotheses, nicotine enhanced the effectiveness of
      positive primes to bias first gaze-fixations (FGFs) toward neutral pictures
      relative to negative pictures and attenuated the effectiveness of negative primes
      on FGFs toward negative pictures, but did not bias performance in the CAP task
      where competing target stimuli were not present. These effects of nicotine on
      affective priming and attentional bias toward competing reinforcers may
      contribute to smoking motivation.

PMID- 20158295
TI  - Testing the influence of external and internal cues on smoking motivation using a
      community sample.
AB  - Exposing smokers to either external cues (e.g., pictures of cigarettes) or
      internal cues (e.g., negative affect induction) can induce urge to smoke and
      other behavioral and physiological responses. However, little is known about
      whether the two types of cues interact when presented in close proximity, as is
      likely the case in the real word. Additionally, potential moderators of cue
      reactivity have rarely been examined. Finally, few cue-reactivity studies have
      used representative samples of smokers. In a randomized 2 x 2 crossed factorial
      between-subjects design, the current study tested the effects of a negative
      affect cue intended to produce anxiety (speech preparation task) and an external
      smoking cue on urge and behavioral reactivity in a community sample of adult
      smokers (N = 175), and whether trait impulsivity moderated the effects. Both
      types of cues produced main effects on urges to smoke, despite the speech task
      failing to increase anxiety significantly. The speech task increased smoking urge
      related to anticipation of negative affect relief, whereas the external smoking
      cues increased urges related to anticipation of pleasure; however, the cues did
      not interact. Impulsivity measures predicted urge and other smoking-related
      variables, but did not moderate cue-reactivity. Results suggest independent
      rather than synergistic effects of these contributors to smoking motivation.

PMID- 20158296
TI  - Enhanced sensitivity of the MRL/MpJ mouse to the neuroplastic and behavioral
      effects of acute and chronic antidepressant treatments.
AB  - Adult hippocampal neurogenesis has been implicated in the pathophysiology of
      depression and in the therapeutic effects of antidepressant drugs. Current
      immunohistochemical methods that study neurogenesis are time consuming and labor
      intensive. Therefore, a significantly more rapid flow cytometric method was
      characterized to measure neurogenesis in the adult mouse brain. The sensitivity
      of mice to the effects of antidepressant treatments is dependent on genetic
      background. Thus, studies were conducted comparing the responsiveness of 2 inbred
      mouse strains, MRL/MpJ and C57BL/6J, to the acute and chronic effects of
      antidepressants on neurochemistry and behavior. Acutely, MRL/MpJ mice displayed
      more robust behavioral and neurochemical responses to pharmacologically distinct
      antidepressants than C57BL/6J mice. Chronic administration of the antidepressant
      drugs fluoxetine and desipramine produced robust elevations in hippocampal cell
      proliferation and brain-derived neurotrophic factor (BDNF) protein levels in
      MRL/MpJ mice. C57BL/6J mice treated similarly with antidepressant drugs were
      mainly unresponsive on these measures. Mice were tested in the novelty-induced
      hypophagia (NIH) paradigm to examine a behavioral response associated with
      chronic, but not acute, antidepressant treatment. Only MRL/MpJ mice were
      behaviorally responsive to chronic antidepressant administration in the NIH
      paradigm. The positive effects of chronic antidepressants on hippocampal cell
      proliferation and BDNF paralleled the ability of these drugs to produce changes
      in NIH behavior. These studies highlight the advantages of using flow cytometry
      to study hippocampal neurogenesis and identify the MRL/MpJ mouse as a strain with
      superior response to antidepressant drug treatments that may lead to a better
      understanding of the genetics behind antidepressant efficacy and sensitivity.

PMID- 20158297
TI  - Effects of acute progesterone administration upon responses to acute psychosocial
      stress in men.
AB  - Animal studies suggest that neuroactive steroids, in particular progesterone and
      its metabolites, have stress-dampening effects. However, few studies have
      explored these effects in humans. In this study, we investigated the effects of
      acute progesterone administration on responses to the Trier Social Stress Test
      (TSST). Healthy men participated in the TSST 3.5 hrs after intramuscular
      injection of 0, 50, or 100 mg progesterone (N = 16, 14, and 14). We measured
      cardiovascular (heart rate, blood pressure), hormonal (plasma
      adrenocorticotrophic hormone, cortisol, and noradrenaline), and subjective (e.g.,
      anxiety, arousal) responses to stress in the three groups. Before the TSST,
      progesterone injections increased plasma levels without altering physiological or
      subjective states. Stress produced its expected physiological and subjective
      effects among placebo-treated individuals. Progesterone 50 mg attenuated peak
      increases in plasma cortisol and reduced changes in negative mood and alertness
      after stress, yet it increased plasma noradrenaline and systolic blood pressure.
      Progesterone 100 mg also attenuated stress-induced increases in alertness and
      arousal, yet it potentiated stress-induced increases in diastolic pressure. Thus,
      progesterone dampened some of the psychological effects of stress but produced
      inconsistent effects on physiological stress responses.

PMID- 20158298
TI  - Computer-assisted cognitive rehabilitation for the treatment of patients with
      substance use disorders: a randomized clinical trial.
AB  - The purpose of this study was to examine the comparative efficacy of cognitive
      rehabilitation as an intervention for substance misuse. Patients with substance
      use disorders entering long-term residential care (N = 160) were randomly
      assigned to one of two conditions: (a) standard treatment plus computer-assisted
      cognitive rehabilitation (CACR), which was designed to improve cognitive
      performance in areas such as problem solving, attention, memory, and information
      processing speed; and (b) an equally intensive attention control condition
      consisting of standard treatment plus a computer-assisted typing tutorial (CATT).
      Participants were assessed at baseline, during treatment, at treatment
      completion, and 3-, 6-, 9-, and 12-month follow-up. Intent-to-treat analyses
      showed that, compared with those randomized to CATT, patients who received CACR
      were significantly more engaged in treatment (e.g., higher ratings of positive
      participation by treatment staff, higher ratings of therapeutic alliance), more
      committed to treatment (e.g., longer stays in residence) and reported better long
      term outcomes (e.g., higher percentage of days abstinent after treatment).
      Mediational analyses revealed the positive comparative effect of CACR on
      abstinence during the year after treatment was mediated by treatment engagement
      and length of stay in residence.

PMID- 20158299
TI  - Delay discounting in current and former marijuana-dependent individuals.
AB  - Studies have found that a variety of drug-dependent groups discount delayed
      rewards more than matched controls. This study compared delay discounting for a
      hypothetical $1,000 reward among dependent marijuana users, former dependent
      marijuana users, and matched controls. Discounting of marijuana was also assessed
      in the currently marijuana-dependent group. No significant differences in
      discounting were detected among the groups; however, currently dependent users
      showed a trend to discount money more than the other 2 groups. Within the
      dependent marijuana group, marijuana was discounted more than money, and
      discounting for money and marijuana was significantly and positively correlated.
      Regression analyses indicated that delay discounting was more closely associated
      with tobacco use than marijuana use. A variety of questionnaires were also
      administered, including impulsivity questionnaires. Dependent marijuana users
      scored as significantly more impulsive on the Impulsiveness subscale of the
      Eysenck Impulsiveness-Venturesomeness-Empathy questionnaire than controls.
      However, the 3 groups did not significantly differ on several other personality
      questionnaires, including the Barratt Impulsivity Scale-11. The Stanford Time
      Perception Inventory Present-Fatalistic subscale was positively correlated with
      money and marijuana discounting, indicating that a greater sense of powerlessness
      over the future is related to greater delay discounting. Results suggest that
      current marijuana dependence may be associated with a trend toward increased
      delay discounting, but this effect size appears to be smaller for marijuana than
      for previously examined drugs.

PMID- 20158303
TI  - Common genes contribute to depressive symptoms and heart rate variability: the
      Twins Heart Study.
AB  - Depression and reduced heart rate variability (HRV) are predictors of coronary
      artery disease (CAD), and highly correlated with each other. However, little is
      known to what extend this correlation can be explained by common genetic
      components. We examined 198 middle-aged male twins (121 monozygotic and 77
      dizygotic) from the Vietnam Era Twin Registry. Current depressive symptoms were
      assessed using the Beck Depression Inventory-II and HRV was assessed on 24-hour
      electrocardiographic Holter recordings. Five frequency domain variables were
      used, including ultra low frequency (ULF), very low frequency (VLF), low
      frequency (LF), high frequency (HF) and total power (TPow). Structural equation
      modeling was used to estimate shared genetic effects for depressive symptoms and
      the HRV frequency domains. Both depressive symptoms (h(2)=.5) and all
      measurements of HRV showed high heritability (h(2)=.43-.63). A significant
      inverse correlation was found between depressive symptoms and all HRV indices
      except LF and HF, with the highest coefficient (r) for TPow (r = -.24, P = .01)
      and ULF (r = -.24, P = .01). Bivariate genetic modeling revealed significant
      genetic correlations between depressive symptoms and TPow (r(A) = -.21, P = .04),
      as well as ULF (r(A) = -.23, P = .02). Of the total covariance between depressive
      symptoms and these two HRV indices, over 80% was due to the same genetic factors.
      In conclusion, depressive symptoms are associated with decreased HRV and this
      association is due, in large part, to a shared genetic effect. These results
      suggest that a common neurobiological dysfunction links depression and autonomic
      dysregulation.

PMID- 20158305
TI  - Associations between ADH gene variants and alcohol phenotypes in Dutch adults.
AB  - Recently, Macgregor et al. (2009) demonstrated significant associations of ADH
      polymorphisms with reactions to alcohol and alcohol consumption measures in an
      Australian sample. The aim of the present study was to replicate these findings
      in a Dutch sample. Survey data on alcohol phenotypes came from 1,754 unrelated
      individuals registered with the Netherlands Twin Register. SNPs in the ADH gene
      cluster located on chromosome 4q (n = 491) were subdivided in seven gene sets:
      ADH5, ADH4, ADH6, ADH1A, ADH1B, ADH1C and ADH7. Within these sets associations of
      SNPs with alcohol consumption measures, age at onset variables, reactions to
      alcohol and problem drinking liability were examined. Of the original 38 SNPs
      studied by Macgregor et al. (2009), six SNPs were not available in our dataset,
      because one of them had a minor allele frequency < .01 (rs1229984) and five could
      not be imputed. The remaining SNP associations with alcohol phenotypes as
      identified by Macgregor et al. (2009) were not replicated in the Dutch sample,
      after correcting for multiple genotype and phenotype testing. Significant
      associations were found however, for reactions to alcohol with a SNP in ADH5
      (rs6827292, p = .001) and a SNP just upstream of ADH5 (rs6819724, p = .0007) that
      is in strong LD with rs6827292. Furthermore, an association between age at onset
      of regular alcohol use and a SNP just upstream of ADH7 (rs2654849, p = .003) was
      observed. No significant associations were found for alcohol consumption and
      problem drinking liability. Although these findings do not replicate the earlier
      findings at the SNP level, the results confirm the role of the ADH gene cluster
      in alcohol phenotypes.

PMID- 20158304
TI  - A genomewide association study of nicotine and alcohol dependence in Australian
      and Dutch populations.
AB  - Persistent tobacco use and excessive alcohol consumption are major public health
      concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically
      influenced complex disorders that exhibit a high degree of comorbidity. To
      identify gene variants contributing to one or both of these addictions, we first
      conducted a pooling-based genomewide association study (GWAS) in an Australian
      population, using Illumina Infinium 1M arrays. Allele frequency differences were
      compared between pooled DNA from case and control groups for: (1) AD, 1224 cases
      and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and
      ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent
      samples from the Netherlands for AD and for ND. Thirdly, we performed a meta
      analysis of the 10,000 most significant AD- and ND-related SNPs from the
      Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide
      significance (p < 5 x 10(-8)) for ND (rs964170 in ARHGAP10 on chromosome 4, p =
      4.43 x 10(-8)) and three others for comorbid AD/ND (rs7530302 near MARK1 on
      chromosome 1 (p = 1.90 x 10(-9)), rs1784300 near DDX6 on chromosome 11 (p = 2.60
      x 10(-9)) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10(-8))). None
      of the SNPs achieved genomewide significance in the Australian/Dutch meta
      analysis, but a gene network diagram based on the top-results revealed
      overrepresentation of genes coding for ion-channels and cell adhesion molecules.
      Further studies will be required before the detailed causes of comorbidity
      between AD and ND are understood.

PMID- 20158306
TI  - Variation at 8q24 and 9p24 and risk of epithelial ovarian cancer.
AB  - The chromosome 8q24 region (specifically, 8q24.21.a) is known to harbor variants
      associated with risk of breast, colorectal, prostate, and bladder cancers. In
      2008, variants rs10505477 and rs6983267 in this region were associated with
      increased risk of invasive ovarian cancer (p < 0.01); however, three subsequent
      ovarian cancer reports of 8q24 variants were null. Here, we used a multi-site
      case-control study of 940 ovarian cancer cases and 1,041 controls to evaluate
      associations between these and other single-nucleotide polymorphisms (SNPs) in
      this 8q24 region, as well as in the 9p24 colorectal cancer associated-region
      (specifically, 9p24.1.b). A total of 35 SNPs from previous reports and additional
      tagging SNPs were assessed using an Illumina GoldenGate array and analyzed using
      logistic regression models, adjusting for population structure and other
      potential confounders. We observed no association between genotypes and risk of
      ovarian cancer considering all cases, invasive cases, or invasive serous cases.
      For example, at 8q24 SNPs rs10505477 and rs6983267, analyses yielded per-allele
      invasive cancer odds ratios of 0.95 (95% confidence interval (CI) 0.82-1.09, p
      trend 0.46) and 0.97 (95% CI 0.84-1.12, p trend 0.69), respectively. Analyses
      using an approach identical to that of the first positive 8q24 report also
      yielded no association with risk of ovarian cancer. In the 9p24 region, no SNPs
      were associated with risk of ovarian cancer overall or with invasive or invasive
      serous disease (all p values > 0.10). These results indicate that the SNPs
      studied here are not related to risk of this gynecologic malignancy and that the
      site-specific nature of 8q24.21.a associations may not include ovarian cancer.

PMID- 20158307
TI  - Clustering of trauma and associations with single and co-occurring depression and
      panic attack over twenty years.
AB  - Individuals who experience one type of trauma often experience other types, yet
      few studies have examined the clustering of trauma. This study examines the
      clustering of traumatic events and associations of trauma with risk for single
      and co-occurring major depressive disorder (MDD) and panic attack for 20 years
      after first trauma. Lifetime histories of MDD, panic attack, and traumatic events
      were obtained from participants in an Australian twin sample. Latent class
      analysis was used to derive trauma classes based on each respondent's trauma
      history. Associations of the resulting classes and of parental alcohol problems
      and familial effects with risk for a first onset of single and co-occurring MDD
      and panic attack were examined from the year of first trauma to 20 years later.
      Traumatic events clustered into three distinct classes characterized by
      endorsement of little or no trauma, primarily nonassaultive, and primarily
      assaultive events. Individuals in the assaultive class were characterized by a
      younger age at first trauma, a greater number of traumatic events, and high rates
      of parental alcohol problems. Members of the assaultive trauma class had the
      strongest and most enduring risk for single and co-occurring lifetime MDD and
      panic attack. Assaultive trauma outweighed associations of familial effects and
      nonassaultive trauma with risk for 10 years following first trauma.

PMID- 20158308
TI  - Phenotypic and genetic relations between the HEXACO dimensions and trait
      emotional intelligence.
AB  - The present study investigated the location of trait emotional intelligence
      (trait EI or trait emotional self-efficacy) within the context of the HEXACO
      model - a more comprehensive personality framework than the conventional Big Five
      structure. A total of 666 MZ and 526 DZ adult twin pairs from the United Kingdom
      completed the short form of the Trait Emotional Intelligence Questionnaire
      (TEIQue-SF) and the short form of the HEXACO Personality Inventory (HEXACO-60).
      Many significant phenotypic correlations between the TEIQue-SF and the HEXACO-60
      were obtained, which were strongest for HEXACO Extraversion, and weakest for
      HEXACO Honesty-Humility. As was expected, Emotionality was the only HEXACO
      dimension to correlate negatively with TEIQue-SF scores. Bivariate behavioral
      genetic analyses revealed that all phenotypic correlations were attributable to
      common genetic and common nonshared environmental factors. The study confirms the
      validity of trait EI as a constellation of emotional self-perceptions located at
      the lower levels of personality.

PMID- 20158309
TI  - Gemini: a UK twin birth cohort with a focus on early childhood weight
      trajectories, appetite and the family environment.
AB  - Gemini is a cohort study of young twins in the United Kingdom designed to assess
      genetic and environmental influences on early childhood weight trajectories with
      a focus on infant appetite and the family environment. A total of 2402 families
      with twins born in England and Wales between March and December 2007 agreed to
      participate and returned completed baseline questionnaires. The sample includes
      1586 same-sex and 816 opposite-sex twins. The study is currently funded for 5
      years of follow-up, but is planned to continue into early adolescence and beyond,
      pending funding. With current funding of the study, families will be followed up
      when twins are: 8 months old (baseline), and then at 15, 20, 24, 36 and 48 months
      of age. Gemini is in its early stages, with baseline and first follow-up data
      collection completed. This is the first twin cohort to focus on childhood weight
      gain with detailed and repeated measures of children's appetite, food
      preferences, activity behavior and parental feeding styles, alongside detailed
      and repeated collection of anthropometrics. This article reviews the rationale
      for the Gemini study, its representativeness and the main measures.

PMID- 20158310
TI  - A twin-singleton comparison of developmental trajectories of externalizing and
      internalizing problems in 6- to 12-year-old children.
AB  - Research on twin-singleton differences in externalizing and internalizing
      problems in childhood is largely cross-sectional and yields contrasting results.
      The goal of this study was to compare developmental trajectories of externalizing
      and internalizing problems in 6- to 12-year-old twins and singletons. Child
      Behavior Checklist (CBCL) maternal reports of externalizing and internalizing
      problems were obtained for a sample of 9651 twins from the Netherlands Twin
      Register and for a representative general population sample of 1351 singletons.
      Latent growth modeling was applied to estimate growth curves for twins and
      singletons. Twin-singleton differences in the intercepts and slopes of the growth
      curves were examined. The developmental trajectories of externalizing problems
      showed a linear decrease over time, and were not significantly different for
      twins and singletons. Internalizing problems seem to develop similarly for twins
      and singletons up to age 9. After this age twins' internalizing symptoms start to
      decrease in comparison to those of singletons, resulting in less internalizing
      problems than singletons by the age of 12 years. Our findings confirm the
      generalizability of twin studies to singleton populations with regard to
      externalizing problems in middle and late childhood. The generalizability of
      studies on internalizing problems in early adolescence in twin samples should be
      addressed with care. Twinship may be a protective factor in the development of
      internalizing problems during early adolescence.

PMID- 20158311
TI  - Differences in anthropometric measurements between Sudanese newborn twins and
      singletons.
AB  - Twin pregnancies are associated with disturbed fetal growth and a higher risk of
      low birthweight (LBW), which is one of the most important determinants of
      perinatal morbidity and mortality in Africa. In this study, we compare
      anthropometric measurements in Sudanese twins and their mothers with singletons.
      METHODS: In 1000 Sudanese mothers with singleton births and 30 mothers with
      twins, maternal (weight, height, mid-arm circumference) and 11 newborn
      anthropometric measurements were taken within 24 hours of delivery. Maternal
      education and socio-economic status were additionally recorded. RESULTS: Mothers
      of twins had a significantly higher body weight (p = .045) and lean body mass (p
      = .02) after delivery, and were from higher social classes in general (p = .014).
      In addition to gestational age, twins displayed a statistically significant
      reduction in all anthropometric data, compared to singletons, mainly in terms of
      birth-weight, chest and head circumference, whereas differences in triceps and
      subscapular skin fold thickness and ponderal index were distinctly lower. The LBW
      rate in twins was markedly higher than that in singletons (43.3% vs. 8.3%, p <
      .001). In 20 out of 30 twins (66.7%), Twin A weighed more than Twin B (difference
      (SD) of 443 (335) g), and in the remaining 10 cases (33.7%), the weight of Twin B
      was equal to or more than that of twin A (difference (SD) of 211 (240) g, p =
      .039). In unlike-sex pairs, the mean (SD) difference between Twins A and B in
      birthweight was 459 (481) g, which was distinctly higher, compared to same-sex
      pairs (boys, 180 (325) g and girls, 36 (413) g). CONCLUSIONS: Sudanese twins
      displayed significantly reduced anthropometric measurements compared to
      singletons, but to different degrees. Gender had a higher impact on birthweight
      in twins than in singletons.

PMID- 20158312
TI  - Physical features observation: is it repeatable in zygosity determination of
      Chinese adult twins?
AB  - This study reports on the inter- and intrarater reliability of physical features
      observation. Study subjects were 176 Chinese adult persons, consisting of 89
      males and 87 females. Three trained research assistants responded simultaneously
      and respectively to 12 items regarding the subject's physical features including
      'hair', 'Mongoloid folds', left and right 'ear lobes', 'earwax', 'nostril shape',
      'tongue rolling', left and right 'hitchhiker's thumb', 'mid-digital hair' and
      left and right 'simian crease' at the moment of interview. And 14 days later,
      these subjects received the same observation once again. The results showed that
      the inter- and intra-observer agreements of 'hair', 'earwax', 'tongue rolling',
      'mid-digital hair' and 'simian crease' were almost perfect with most kappa
      (kappa) coefficients >or= .80, while 'Mongoloid fold' and 'nostril shape' showed
      poor inter-observer agreement and 'nostril shape' showed poor intra-observer
      agreement (kappa < .40). Two other physical features, 'hitchhiker's thumb' and
      'ear lobes' showed moderate inter-observer agreement and three features,
      'hitchhiker's thumb', 'ear lobes' and 'Mongoloid fold', showed moderate intra
      observer agreement (.40<or= kappa <.80). In conclusion, this study suggests that
      as far as reliability is concerned, the five features which were 'hair',
      'earwax', 'tongue rolling', 'mid-digital hair' and 'simian crease' could be
      considered in zygosity determination of Chinese adult twins, while the two
      features, 'Mongoloid fold' and 'nostril shape', should be abandoned.

PMID- 20158313
TI  - Secondary sex ratio in multiple births.
AB  - Attempts have been made to identify factors influencing the sex ratio at birth
      (number of males per 100 females). Statistical analyses have shown that
      comparisons between sex ratios demand large data sets. The secondary sex ratio
      has been believed to vary inversely with the frequency of prenatal losses. This
      hypothesis suggests that the ratio is highest among singletons, medium among
      twins and lowest among triplets. Birth data in Sweden for the period 1869-2004
      showed that among live births the secondary sex ratio was on average 105.9 among
      singletons, 103.2 among twins and 99.1 among triplets. The secondary sex ratio
      among stillbirths for both singletons and twins started at a high level, around
      130, in the 1860s, but approached live birth values in the 1990s. This trend is
      associated with the decrease and convergence of stillbirth rates among males and
      females. For detailed studies, we considered data for Sweden in 1869-1878 and in
      1901-1967. Marital status or place of residence (urban or rural) had no marked
      influence on the secondary sex ratio among twins. For triplets, the sex ratio
      showed large random fluctuations and was on average low. During the period 1901
      1967, 20 quadruplet, two quintuplet and one sextuplet set were registered. The
      sex ratio was low, around 92.0.

PMID- 20158314
TI  - Low rate of cerebral injury in monochorionic twins with selective intrauterine
      growth restriction.
AB  - This study was conducted to determine the incidence of cerebral injury as
      detected by postnatal brain scan in monochorionic twins with selective
      intrauterine growth restriction. Having excluded cases complicated with twin-to
      twin transfusion syndrome and one co-twin suffering intrauterine fetal death, a
      total of 73 monochorionic twin pregnancies divided into absence (group I, n = 46)
      or presence (group II, n = 27) of selective intrauterine growth restriction. Mild
      cerebral injury was defined as presenting one of the following abnormal cranial
      scan findings: intraventricular hemorrhage grade I, grade II, lenticulostiate
      vasculopathy and/or subependymal pseudocysts, while severe cerebral injury was
      defined as presenting intraventricular hemorrhage grade III, grade IV, cystic
      periventricular leukomalacia (PVL) grade II or higher, porencephalic cysts,
      and/or ventricular dilatation. The incidence of mild cerebral injury was not
      significantly different between these two groups (eight cases in group I and six
      cases in group II). Except for one case that later developed a seizure, the
      majority (13 out of 14) of cases with minor brain scan anomalies were only
      transient, without significant clinical impact. There was only one case diagnosed
      with a major brain scan anomaly (periventricular leukomalacia) in group II. One
      severe brain injury and three neonatal deaths all belonged to group II with
      abnormal umbilical artery Doppler in the growth restricted twin. In conclusion,
      the incidence of severe cerebral injury in monochorionic twin pregnancies with
      selective intrauterine growth restriction was low, at 3.7%.

PMID- 20158315
TI  - Twins switched at birth: a case from the Canary Islands.
AB  - Monozygotic (MZ) twins switched at birth represent a rare class of twins who are
      reared apart and reunited (MZA). Background data and descriptive findings from a
      case study of such a pair, born thirty-six years ago in the Canary Islands, are
      presented.

PMID- 20158316
TI  - Bisphosphonate-coated BSA nanoparticles lack bone targeting after systemic
      administration.
AB  - A polymeric conjugate of polyethyleneimine-graft-poly(ethylene glycol) and 2-(3
      mercaptopropylsulfanyl)-ethyl-1,1-bisphosphonic acid (PEI-PEG-thiolBP) was
      prepared and used for surface coating of bovine serum albumin (BSA) nanoparticles
      (NPs) designed for bone-specific delivery of bone morphogenetic protein-2 (BMP
      2). The NP coating was achieved with a dialysis and an evaporation method, and
      the obtained NPs were characterized by particle size, zeta-potential, morphology,
      and cytotoxicity in vitro. The particle size and surface charge of the NPs could
      be effectively tuned by the PEG and thiolBP substitution ratios of the conjugate,
      the coating method, and the polymer concentration used for coating. The PEG
      modification on PEI reduced the toxicity of PEI and the coated NPs, based on in
      vitro assessment with human C2C12 cells and rat bone marrow stromal cells. On the
      basis of an alkaline phosphatase (ALP) induction assay, the NP-encapsulated BMP-2
      displayed full retention of its bioactivity, except for BMP-2 in PEI-coated NPs.
      By encapsulating (125)I-labeled BMP-2, the polymer-coated NPs were assessed for
      hydroxyapatite (HA) affinity; all NP-encapsulated BMP-2 showed significant
      affinity to HA as compared with free BMP-2 in vitro, and the PEI-PEG-thiolBP
      coated NPs improved the in vivo retention of BMP-2 compared with uncoated NPs.
      However, the biodistribution of NPs after intravenous injection in a rat model
      indicated no beneficial effects of thiolBP-coated NPs for bone targeting. Our
      results suggested that the BP-conjugated NPs are useful for localized delivery of
      BMP-2 in bone repair and regeneration, but they are not effective for bone
      targeting after intravenous administration.

PMID- 20158317
TI  - The association between achieving low-density lipoprotein cholesterol (LDL-C)
      goal and statin treatment in an employee population.
AB  - Statin medications are recommended for patients who have not achieved low-density
      lipoprotein cholesterol (LDL-C) goals through lifestyle modifications. The
      objective of this retrospective observational study was to examine statin
      medication usage patterns and the relationship with LDL-C goal levels (according
      to Adult Treatment Panel III guidelines) among a cohort of employees of a major
      financial services corporation. From 1995 to 2004, a total of 1607 executives
      participated in a periodic health examination program. An index date was assigned
      for each study participant (date of their exam) and statin medication usage was
      determined from the pharmacy claims database for 365 days before the index date.
      Patients were identified as adherent to statins if the medication possession
      ratio was > or =80%. In all, 150 (9.3%) executives filled at least 1 statin
      prescription in the 365 days prior to their exam. A total of 102 statin users
      (68%) were adherent to statin medication. Among all executives who received
      statin treatment, 70% (odds ratio [OR] = 2.30, 95% confidence interval [CI] =
      1.82, 2.90) achieved near-optimal (<130 mg/dL) and 30% (OR = 1.78, 95% CI = 1.15,
      2.76) achieved optimal (<100 mg/dL) LDL-C goals, which is significantly higher
      than the rates among statin nonusers (55% and 21%). Adherent statin users were
      more likely to achieve recommended near-optimal LDL-C goals compared to statin
      nonusers (overall P = 0.002; adherent: OR = 2.75, 95% CI = 1.662, 4.550), while
      nonadherent statin users were more likely to achieve the optimal goal compared to
      statin nonusers (OR = 2.223; CI = 1.145, 4.313). Statin usage was associated with
      improvements in LDL-C goal attainment among executives who participated in a
      periodic health examination. Appropriate statin medication adherence should be
      encouraged in working populations in order to achieve LDL-C goals.

PMID- 20158318
TI  - Indirect costs associated with surgery for low back pain-a secondary analysis of
      clinical trial data.
AB  - This study examines the indirect costs associated with surgery for axial low back
      pain using data obtained from a prospective multicenter clinical trial that
      compared Charite artificial disc replacement with anterior lumbar interbody
      fusion using iliac crest bone graft. While 75% of study subjects reported full-
      or part-time employment prior to surgery, this percentage dropped to 45% at 6
      weeks postoperatively. Return to preoperative employment levels occurred at
      approximately 6 months postoperatively. Two years after surgery, employment
      levels were 16% higher than preoperative levels. Lost productivity related to
      absenteeism resulted in lost wages averaging $2884 per patient during the first
      postoperative year. Although short-term indirect costs of surgery are substantial
      from a societal perspective, the higher employment rate at 2 years suggests a
      long-term economic benefit. The findings demonstrate the significant, though not
      surprising, impact of spinal disability on productivity, and the importance of
      including measurement of lost productivity and return to work in the economic
      evaluation of related interventions.

PMID- 20158319
TI  - Burden of chronic sleep maintenance insomnia characterized by nighttime
      awakenings.
AB  - The objective of this study was to evaluate the economic and humanistic burden of
      chronic sleep maintenance insomnia characterized by nighttime awakenings (CINA).
      A database analysis of National Health and Wellness Survey, an annual cross
      sectional study of health status and outcomes of US adults, was performed. CINA
      was defined as experiencing nighttime awakenings at least twice per week for more
      than 1 month that have moderate to severe impact on daily life and not
      experiencing difficulty falling asleep. No insomnia was defined as not self
      reporting insomnia, sleep difficulties, or sleep symptoms. Outcomes included
      resource utilization in the past 6 months, the Work Productivity and Activity
      Impairment questionnaire, and the SF-8. Linear regression models were developed
      to assess the independent effects of CINA on outcomes while controlling for
      demographics and comorbidity. In all, 1523 respondents met the criteria for CINA
      and 24,106 met the criteria for no insomnia. Controlling for demographics and
      comorbidity, CINA sufferers had greater resource utilization (0.1 [P < 0.001]
      more emergency room visits, 0.2 [P = 0.001] more days hospitalized, and 2.5 [P <
      0.001] more provider visits), 22.4% (P < 0.001) greater activity impairment, and
      SF-8 physical and mental summary scores that were 6.2 (P < 0.001) and 6.8 (P <
      0.001) points lower than those with no insomnia, respectively. Among those
      employed full time, CINA sufferers had greater work productivity impairment (4.0%
      due to absenteeism, 17.6% due to presenteeism, and 15.6% greater overall
      productivity impairment) than those with no insomnia (P < 0.001 for all). CINA in
      relative isolation was associated with a significant negative impact on health
      care utilization and its associated costs, health-related quality 16 of life, and
      work productivity.

PMID- 20158320
TI  - Is pharmacologic care of chronic obstructive pulmonary disease consistent with
      the guidelines?
AB  - Chronic obstructive pulmonary disease (COPD) is a common chronic illness that
      affects an estimated 210 million people worldwide, including 12 million people in
      the United States. National and international guidelines for treatment of COPD
      recommend use of certain medications, especially bronchodilators and
      corticosteroids, but the extent to which these are used appropriately is largely
      unknown. The objective of this study was to determine the extent to which
      pharmacotherapy for COPD is consistent with guidelines. Individuals with COPD (N
      = 2272), enrolled for at least 2 years in a large midwestern managed care
      organization, were identified from medical claims data. Medications dispensed in
      2003 were examined using National Drug Codes from dispensation records. Quality
      indictors, developed from guidelines, focused on (1) use of bronchodilators, (2)
      use of inhaled corticosteroids (ICS) for patients with frequent exacerbations,
      and (3) use of systemic corticosteroids for acute exacerbation of COPD (AE-COPD).
      A total of 2272 subjects aged 45 years or older with a diagnosis of COPD were
      identified. Seventy-two percent of subjects with COPD received at least 1
      bronchodilator; 64% of subjects with frequent prior exacerbations (> or =3 in the
      past year) received ICS; and only 51% of subjects with AE-COPD during the study
      year received systemic corticosteroids. Although most patients received 1 or more
      respiratory medications recommended by the guidelines, there were gaps in care
      including limited use of systemic corticosteroids for AE-COPD and ICS for
      patients with frequent exacerbations. Greater use of appropriate medications
      could lead to improved health for patients with COPD.

PMID- 20158321
TI  - The reliability of patient-reported pregnancy outcome data.
AB  - Pregnancy and neonatal outcome information is frequently used in disease
      management to evaluate the cost-effectiveness of prenatal interventions and for
      other research and reporting activities. The purpose of this study was to
      determine if a telephone interview process is a reliable methodology for
      collecting pregnancy outcomes. High-risk patients from a large maternal-fetal
      medicine practice who received outpatient preterm labor management services from
      January 1996 to June 2001 were identified. Patient-reported pregnancy outcome
      data for 285 mothers and 478 infants were collected via a telephone interview by
      a perinatal nurse and compared to pregnancy outcome data abstracted from the
      maternal and infant hospital records. Overall, concordance and/or Kappa
      coefficients between maternal report and the medical record were high for
      delivery date (96.4%), birth weight within 100 grams (88.9%), Cesarean delivery
      (99.0%, Kappa = 0.98), and high-level nursery admission (91.2%, Kappa = 0.82).
      Both singleton and multiple gestation types accurately reported pregnancy outcome
      information. A telephone interview with a skilled nurse can be a reliable
      methodology for collection of valuable clinical and research data related to
      pregnancy outcome. Data collected in this manner and maintained in a database may
      be used with a high level of confidence by health care providers, payers, and
      researchers.

PMID- 20158322
TI  - An actuarial approach to comparing early stage and late stage lung cancer
      mortality and survival.
AB  - Comparing the mortality characteristics of different cohorts is an essential
      process in the life insurance industry. Pseudodisease, lead-time bias, and length
      bias, which are critical to determining the value of cancer screening, have close
      analogues in life insurance company management, including the temporal impact of
      underwriting. Ratios of all-cause mortality rates for cancer cohorts relative to
      standard population mortality rates can provide insights into early stage and
      late stage mortality differences, differences by age, sex, race, and histology,
      and allow modeling of biases associated with early stage detection or screening
      protocols. The Surveillance, Epidemiology and End Results (SEER) data set has
      characteristics that allow efficient application of actuarial techniques. We show
      the mortality burden associated with treated early stage lung cancer and that
      identifying all lung cancers at early stage could reduce US lung cancer deaths by
      over 70,000 per year.

PMID- 20158323
TI  - The relationship among body mass index, subjective reporting of chronic disease,
      and the use of health care services in Newfoundland and Labrador, Canada.
AB  - The purpose of the study was to examine the association of body mass index (BMI)
      with the prevalence of chronic disease and health services use in adults living
      in Newfoundland and Labrador (NL). A cross-sectional analysis of 2345 adult
      respondents to the 2001 Canadian Community Health Survey was performed. Outcome
      measures included the prevalence of chronic disease and health services use. The
      sample comprised normal (37%), overweight (39%), obese (17%), and morbidly obese
      (6%) individuals. Obese and morbidly obese individuals were more likely to report
      the presence of a chronic disease. Adjusting for age and sex, increasing BMI
      category was significantly associated with a greater likelihood of
      cardiovascular, endocrine, and pulmonary diseases (excluding asthma). The
      majority of survey respondents in each category reported having a regular doctor
      (>75%), and there were no significant differences across categories. Compared to
      those with a normal BMI, obese and morbidly obese individuals reported a
      significantly higher number of visits to a family physician. There were no
      differences across BMI categories and the use of specialist or hospital services.
      Almost a quarter of the study sample in NL was classified as morbidly obese or
      obese. These individuals reported more chronic conditions and more visits to a
      family physician than the normal-weight group. The greater morbidity and the
      increased frequency of visits to family physicians suggests greater consideration
      should be given to channeling financial and human resources to the primary health
      care of this high-risk population.

PMID- 20158325
TI  - Vector-Borne and Zoonotic Diseases circa 2010: a brave new world.

PMID- 20158326
TI  - Symposium on the ecology of plague and its effects on wildlife: a model for
      translational research.

PMID- 20158327
TI  - Disease limits populations: plague and black-tailed prairie dogs.
AB  - Plague is an exotic vector-borne disease caused by the bacterium Yersinia pestis
      that causes mortality rates approaching 100% in black-tailed prairie dogs
      (Cynomys ludovicianus). We mapped the perimeter of the active portions of black
      tailed prairie dog colonies annually between 1999 and 2005 at four prairie dog
      colony complexes in areas with a history of plague, as well as at two complexes
      that were located outside the distribution of plague at the time of mapping and
      had therefore never been affected by the disease. We hypothesized that the
      presence of plague would significantly reduce overall black-tailed prairie dog
      colony area, reduce the sizes of colonies on these landscapes, and increase
      nearest-neighbor distances between colonies. Within the region historically
      affected by plague, individual colonies were smaller, nearest-neighbor distances
      were greater, and the proportion of potential habitat occupied by active prairie
      dog colonies was smaller than at plague-free sites. Populations that endured
      plague were composed of fewer large colonies (>100 ha) than populations that were
      historically plague free. We suggest that these differences among sites in colony
      size and isolation may slow recolonization after extirpation. At the same time,
      greater intercolony distances may also reduce intercolony transmission of
      pathogens. Reduced transmission among smaller and more distant colonies may
      ultimately enhance long-term prairie dog population persistence in areas where
      plague is present.

PMID- 20158328
TI  - Vector control improves survival of three species of prairie dogs (Cynomys) in
      areas considered enzootic for plague.
AB  - Plague causes periodic epizootics that decimate populations of prairie dogs (PDs)
      (Cynomys), but the means by which the causative bacterium (Yersinia pestis)
      persists between epizootics are poorly understood. Plague epizootics in PDs might
      arise as the result of introductions of Y. pestis from sources outside PD
      colonies. However, it remains possible that plague persists in PDs during
      interepizootic periods and is transmitted at low rates among highly susceptible
      individuals within and between their colonies. If this is true, application of
      vector control to reduce flea numbers might reduce mortality among PDs. To test
      whether vector control enhances PD survival in the absence of obvious plague
      epizootics, we reduced the numbers of fleas (vectors for Y. pestis) 96-98% (1
      month posttreatment) on 15 areas involving three species of PDs (Cynomys
      leucurus, Cynomys parvidens in Utah, and Cynomys ludovicianus in Montana) during
      2000-2004 using deltamethrin dust delivered into burrows as a pulicide. Even
      during years without epizootic plague, PD survival rates at dusted sites were 31
      45% higher for adults and 2-34% higher for juveniles compared to survival rates
      at nondusted sites. Y. pestis was cultured from 49 of the 851 flea pools tested
      (6882 total fleas) and antibodies against Y. pestis were identified in serum
      samples from 40 of 2631 PDs. Although other explanations are possible, including
      transmission of other potentially fatal pathogens by fleas, ticks, or other
      ectoparasites, our results suggest that plague might be maintained indefinitely
      in PD populations in the absence of free epizootics and widespread mortality
      among these animals. If PDs and their fleas support enzootic cycles of plague
      transmission, there would be important implications for the conservation of these
      animals and other species.

PMID- 20158329
TI  - Enzootic plague reduces black-footed ferret (Mustela nigripes) survival in
      Montana.
AB  - Black-footed ferrets (Mustela nigripes) require extensive prairie dog colonies
      (Cynomys spp.) to provide habitat and prey. Epizootic plague kills both prairie
      dogs and ferrets and is a major factor limiting recovery of the highly endangered
      ferret. In addition to epizootics, we hypothesized that enzootic plague, that is,
      presence of disease-causing Yersinia pestis without any noticeable prairie dog
      die off, may also affect ferret survival. We reduced risk of plague on portions
      of two ferret reintroduction areas by conducting flea control for 3 years.
      Beginning in 2004, about half of the ferrets residing on dusted and nondusted
      colonies were vaccinated against plague with an experimental vaccine (F1-V fusion
      protein). We evaluated 6-month reencounter rates (percentage of animals observed
      at the end of an interval that were known alive at the beginning of the
      interval), an index to survival, for ferrets in four treatment groups involving
      all combinations of vaccination and flea control. For captive-reared ferrets (115
      individuals observed across 156 time intervals), reencounter rates were higher
      for vaccinates (0.44) than for nonvaccinates (0.23, p = 0.044) on colonies
      without flea control, but vaccination had no detectable effect on colonies with
      flea control (vaccinates = 0.41, nonvaccinates = 0.42, p = 0.754). Flea control
      resulted in higher reencounter rates for nonvaccinates (p = 0.026), but not for
      vaccinates (p = 0.508). The enhancement of survival due to vaccination or flea
      control supports the hypothesis that enzootic plague reduces ferret survival,
      even when there was no noticeable decline in prairie dog abundance. The
      collective effects of vaccination and flea control compel a conclusion that fleas
      are required for maintenance, and probably transmission, of plague at enzootic
      levels. Other studies have demonstrated similar effects of flea control on
      several species of prairie dogs and, when combined with this study, suggest that
      the effects of enzootic plague are widespread. Finally, we demonstrated that the
      experimental F1-V fusion protein vaccine provides protection to ferrets in the
      wild.

PMID- 20158330
TI  - Mountain plover responses to plague in Montana.
AB  - Plague is a bacterial (Yersinia pestis) disease that causes epizootic die-offs in
      black-tailed prairie dog (Cynomys ludovicianus) populations in the North American
      Great Plains. Through their grazing and burrowing, prairie dogs modify vegetation
      and landscape structure on their colonies in ways that affect other grassland
      species. Plague epizootics on prairie dog colonies can have indirect effects on
      species associated with colonies. The mountain plover (Charadrius montanus)
      preferentially nests on black-tailed prairie dog colonies and is thus negatively
      impacted by the loss of prairie dogs. We studied the effects of plague and colony
      spatial characteristics on the occupancy of 81 prairie dog colonies by nesting
      plovers in Phillips County, Montana, during a 13-year period (1995-2007). We used
      a robust design patch occupancy model to investigate how colony occupancy and
      extinction and colonization rates were affected by plague history, colony size,
      and colony shape. Here extinction and colonization rates refer to the probability
      that a colony loses/gains plovers in a subsequent nesting season, given that it
      had/lacked plovers in that breeding season. Colony occupancy was best explained
      by a model with no annual variation or plague effects. Colony extinction rates
      were driven by a combination of a quadratic of colony area, a 3-year plague
      response, and a measure of colony shape. Conversely, colonization rates were best
      explained by a model with a 4-year plague response. The estimated annual
      proportion of colonies occupied by plovers was 0.75 (95% confidence interval =
      0.57-0.87). Estimated extinction probability ranged from a low of 0.07 (standard
      error [SE] = 0.02) in 2002 to a high of 0.25 (SE = 0.03) in 1995; colonization
      probability ranged from 0.24 (SE = 0.05) in 2006 to 0.35 (SE = 0.05) in 2000. Our
      results highlight how a bird that depends on prairie dogs for nesting habitat
      responds to plague history and other spatial characteristics of the colony.
      Ultimately, this information will broaden our understanding of the impact of
      plague on species other than the host.

PMID- 20158331
TI  - Rodent and flea abundance fail to predict a plague epizootic in black-tailed
      prairie dogs.
AB  - Small rodents are purported to be enzootic hosts of Yersinia pestis and may serve
      as sources of infection to prairie dogs or other epizootic hosts by direct or
      flea-mediated transmission. Recent research has shown that small rodent species
      composition and small rodent flea assemblages are influenced by the presence of
      prairie dogs, with higher relative abundance of both small rodents and fleas at
      prairie dog colony sites compared to grasslands without prairie dogs. However, it
      is unclear if increased rodent or flea abundance predisposes prairie dogs to
      infection with Y. pestis. We tracked rodent and flea occurrence for 3 years at a
      number of prairie dog colony sites in Boulder County, Colorado, before, during,
      and after a local plague epizootic to see if high rodent or flea abundance was
      associated with plague-affected colonies when compared to colonies that escaped
      infection. We found no difference in preepizootic rodent abundance or flea
      prevalence or abundance between plague-positive and plague-negative colonies.
      Further, we saw no significant before-plague/after-plague change in these metrics
      at either plague-positive or plague-negative sites. We did, however, find that
      small rodent species assemblages changed in the year following prairie dog die
      offs at plague-affected colonies when compared to unaffected colonies. In light
      of previous research from this system that has shown that landscape features and
      proximity to recently plagued colonies are significant predictors of plague
      occurrence in prairie dogs, we suggest that landscape context is more important
      to local plague occurrence than are characteristics of rodent or flea species
      assemblages.

PMID- 20158332
TI  - Consumption of baits containing raccoon pox-based plague vaccines protects black
      tailed prairie dogs (Cynomys ludovicianus).
AB  - Baits containing recombinant raccoon poxvirus (RCN) expressing plague antigens
      (fraction 1 [F1] and a truncated form of the V protein-V307) were offered for
      voluntary consumption several times over the course of several months to a group
      of 16 black-tailed prairie dogs (Cynomys ludovicianus). For comparison, another
      group of prairie dogs (n = 12) was injected subcutaneously (SC) (prime and boost)
      with 40 microg of F1-V fusion protein absorbed to alum, a vaccine-adjuvant
      combination demonstrated to elicit immunity to plague in mice and other mammals.
      Control animals received baits containing RCN without the inserted antigen (n =
      8) or injected diluent (n = 7), and as there was no difference in their survival
      rates by Kaplan-Meier analysis, all of them were combined into one group in the
      final analysis. Mean antibody titers to Yersinia pestis F1 and V antigen
      increased (p < 0.05) in the vaccinated groups compared to controls, but titers
      were significantly higher (p < 0.0001) in those receiving injections of F1-V
      fusion protein than in those orally vaccinated with RCN-based vaccine.
      Interestingly, upon challenge with approximately 70,000 cfu of virulent Y.
      pestis, oral vaccination resulted in survival rates that were significantly
      higher (p = 0.025) than the group vaccinated by injection with F1-V fusion
      protein and substantially higher (p < 0.0001) than the control group. These
      results demonstrate that oral vaccination of prairie dogs using RCN-based plague
      vaccines provides significant protection against challenge at dosages that
      simulate simultaneous delivery of the plague bacterium by numerous flea bites.

PMID- 20158333
TI  - Modeling susceptible infective recovered dynamics and plague persistence in
      California rodent-flea communities.
AB  - Plague persists as an enzootic in several very different rodent-flea communities
      around the world. In California, a diversity of rodent-flea communities maintains
      the disease, and a single-host reservoir seems unlikely. Logistic regression of
      plague presence on climate and topographic variables predicts plague in many
      localities where it is absent. Thus, a dynamic community-based analysis was
      needed. Deterministic Susceptible Infective Recovered (SIR) models were adapted
      for plague and analyzed with an eye for insights concerning disease persistence.
      An R simulation program, Plaguesirs, was developed incorporating multihost and
      multivector SIR dynamics, demographic and environmental stochasticity, density
      dependence, and seasonal variation in birth and death. Flea-rodent utilization
      matrices allowed us to get transmission rates as well as flea carrying
      capacities. Rodent densities allowed us to estimate host carrying capacities,
      while maximum birth rates were mainly approximated through an examination of
      litter phenology and demography. We ran a set of simulations to assess the role
      of community structure in maintaining plague in a simulated version of Chuchupate
      campground in Ventura County. Although the actual campground comprises 10 rodent
      and 19 flea species, we focused on a subset suspected to act as a reservoir
      community. This included the vole Microtus californicus, the deer mouse
      Peromyscus maniculatus, the Ceratophyllid fleas Aetheca wagneri and Malareus
      telchinum, and the Leptopsyllid flea Peromyscopsylla hesperomys. The dynamics of
      21 subsets of this community were simulated for 20 years. Single-rodent
      communities showed much lower disease persistence than two-rodent communities.
      However, so long as Malareus was present, endemicity was enhanced; removal of the
      other two fleas slightly increased disease persistence. Two critical features
      improved disease persistence: (1) host breeding season heterogeneity and (2) host
      population augmentation (due to two similar host species instead of one). Voles
      are winter-spring breeders compared to the spring-summer deer mice. While host
      synchronicity may enhance epidemics, host asynchronicity favors endemics.

PMID- 20158334
TI  - Plague in Mongolia.
AB  - Mongolia is a country of Central Asia that occupies 1,564,116 km(2) and has a
      population of 2.7 million people. The geography of Mongolia is varied and has a
      continental climate. Plague, caused by the bacterium Yersinia pestis, is enzootic
      in wild rodent populations over large rural areas of Mongolia. Natural plague
      foci have occurred over 28.3% of Mongolia, and 47.1% of these foci are highly
      active. Highly active plague foci exist mainly in the western part of Mongolia. A
      total of 27% of all plague cultures were isolated from ectoparasites of 12
      species of endemic mammals and 1 species of bird. Most plague cultures isolated
      from ectoparasites of mammals were from fleas (91.5%). The majority of cultures
      isolated from fleas were from marmot fleas (64.5% of all fleas). The marmot flea
      (Oropsylla silantiewi) is considered the primary vector of plague. Human cases of
      plague have been recorded in Mongolia since 1897 and more than 3000 plague
      cultures were isolated from natural foci. Plague foci occur between 50 degrees 00
      43 degrees 00 longitude and 88 degrees 00-120 degrees 00 latitude and at
      altitudes between 640 and 3500 m.

PMID- 20158335
TI  - Study on the movement of Rattus rattus and evaluation of the plague dispersion in
      Madagascar.
AB  - Plague affects mainly the rural areas in the central highlands of Madagascar.
      Rattus rattus is the main rodent host of Yersinia pestis in these localities.
      Since the introduction of plague, endemic foci have continued to expand, and
      spatiotemporal variability in the distribution of human plague has been observed.
      To assess the movements of R. rattus and evaluate the risk of dispersion of the
      disease, a field study at the scale of the habitats (houses, hedges of sisals,
      and rice fields) in the plague villages was carried out during high and low
      seasons of plague transmission to humans. The systemic oral marker Rhodamine B
      was used to follow rats' movements. Baits were placed in different habitats, and
      trapping success was carried out once a month for 3 months after the bait
      distribution. Plague indicators (reservoirs' abundance, flea index, Y. pestis
      prevalence in fleas, and Y. pestis antibody prevalence in rats) were determined.
      The highest abundance of rats and marking efficiency were observed in the sisal
      hedges and the rice fields. Marked rats were captured most commonly near the
      points where baits were initially placed. The main movements of rats were
      observed between the houses and sisal hedges. Major differences were observed
      between the seasons of high and low plague transmission. During the season of low
      plague transmission, rats were more abundant in the sisal hedges and rice fields,
      with rats moving from the houses to the rice fields. During the high plague
      transmission season, rats moved from the hedges of sisal to the rice fields.
      Important indicators of vector abundance and plague transmission were higher
      during the high plague transmission season. The three study habitats were the
      risk areas for plague transmission, but the risk appeared highest in the houses
      and sisals. Rats' movements according to the season were likely directed by the
      availability of food.

PMID- 20158339
TI  - Expression of Ezrin and phosphorylated Ezrin (pEzrin) in pancreatic ductal
      adenocarcinoma.
AB  - It has been suggested that ezrin activation plays a key role in the regulation of
      cancer metastasis. In this study, we immunohistochemically investigated the
      expression patterns of total ezrin and its two phosphorylated forms, pEzrin(-
      Thr567) and pEzrin(- Tyr353), in 66 samples of invasive pancreatic carcinomas and
      11 samples of normal pancreas tissues. Positive expressions of ezrin and pEzrin(-
      Thr567) were detected in most PDAC tissues, significantly higher than that of
      pEzrin(- Tyr353). Furthermore, overexpression of pEzrin(- Tyr353) in pancreatic
      cancers was associated with positive lymph node metastasis, less differentiation,
      pAkt overexpression, and shorter survival times. pEzrin(- Tyr353) may be a potent
      prognosis predictor for pancreatic cancer.

PMID- 20158336
TI  - Recent findings regarding maintenance of enzootic variants of Yersinia pestis in
      sylvatic reservoirs and their significance in the evolution of epidemic plague.
AB  - Despite the widespread presence of bubonic plague in sylvatic reservoirs
      throughout the world, the causative agent (Yersinia pestis) evolved in its
      present form within the last 20,000 years from enteropathogenic Yersinia
      pseudotuberculosis. Comparison of the genomes from the two species revealed that
      Y. pestis possesses only a few unique plasmid-encoded genes that contribute to
      acute disease, whereas this organism has lost about 13% of the chromosomal genes
      that remain active in Y. pseudotuberculosis. These losses reflect readily
      detectable additions, deletions, transpositions, inversions, and acquisition of
      about 70 insertion sequence (IS) inserts, none of which are likely to promote
      increased virulence. In contrast, major enzymes of intermediary metabolism,
      including glucose 6-phosphate dehydrogenase (Zwf ) and aspartase, are present but
      not catalytically functional due to the presence of missense mutations. The
      latter are generally not detectable by the technology of bioinformatics and, in
      the case of Y. pestis, result in radical changes in the metabolic flow of carbon.
      As an important consequence, plague bacilli exhibit a stringent low-calcium
      response characterized by conversion of L-glutamate (and metabolically related
      amino acids) to L-aspartate with secretion of the latter into supernatant fluid
      at 37 degrees C in culture media containing Na(+) but lacking added Ca(2+). This
      phenomenon also occurs in vivo and likely adversely affects the bioenergetics of
      host amino acid pools. Curiously, aspartase is functional in all tested enzootic
      (pestoides) strains of Y. pestis. These isolates are typically restricted to the
      ancient plague reservoirs of Central Asia and Africa and are fully virulent in
      members of the rodent Superfamily Muroidea but avirulent in guinea pigs and man.
      The implications of these findings for the distribution and ecology of Y. pestis
      could be significant.

PMID- 20158340
TI  - Single agent vinflunine in the salvage treatment of patients with castration
      resistant prostate cancer: a phase II trial of the Sarah Cannon research
      consortium.
AB  - Patients with metastatic prostate cancer resistant to hormones and docetaxel were
      treated with vinflunine (320 mg/m(2) every 21 days), a new vinca alkaloid with
      improved preclinical activity. Only 1 of 36 patients (3%) had partial response;
      the median progression-free survival (PFS) was 2.1 months. Treatment was well
      tolerated, with myelosuppression as the only frequent toxicity. Vinflunine has a
      low level of activity in the treatment of refractory metastatic prostate cancer,
      and should not be further developed for this indication.

PMID- 20158342
TI  - Future UK paediatric neurosurgery.
AB  - The sustainability of two currently practices now common in UK paediatric
      neurosurgery are examined. These are service provision by surgeons who also treat
      adults, and provision without a specific on call rota. It is argued that either
      both are sustainable or neither but not one without the other. The consequences
      of these two possibilities are considered. If neither practice is sustainable the
      medium to long term result will be fewer paediatric units with no emergency
      service provided by adult units. If both practices are sustainable there would be
      more paediatric units treating fewer cases each, but a greater likelihood that
      adult only units could continue to provide emergency paediatric surgery.

PMID- 20158345
TI  - Hypopituitarism after brain injury.
AB  - A parent highlights an under-diagnosed complication of traumatic brain injury,
      which she believes led to her son's suicide.

PMID- 20158346
TI  - The European Working Time Directive.

PMID- 20158347
TI  - Prevalence, natural history and consequences of posttraumatic hypopituitarism: a
      case for endocrine surveillance.
AB  - The phenomenon of posttraumatic hypopituitarism (PTHP) has been recognised for
      more than 90 years although it is only in the last decade that systematic study
      of large populations of patients has been undertaken. Knowledge of the prevalence
      and natural history of the condition in survivors of traumatic brain injury (TBI)
      in adult life is expanding rapidly, although the effect of hormone replacement
      therapy is largely unknown. Data relating to injury in childhood are less readily
      available. The symptoms of PTHP and TBI may be indistinguishable in the adult
      patient and biochemical assessment of pituitary function is required for
      diagnosis. These procedures are costly for both the health provider and the
      patient. So can routine assessment of pituitary function be justified? This
      review article considers the current state of knowledge pertaining to prevalence,
      natural history and clinical consequences of PTHP to address this question.

PMID- 20158348
TI  - The long-term outcome of microvascular decompression for trigeminal neuralgia.
AB  - OBJECTIVE: Evaluation of the effectiveness of Microvascular Decompression (MVD)
      for Trigeminal Neuralgia (TGN), with emphasis on patient's perception of outcome,
      and satisfaction with the procedure. MATERIALS AND METHODS: A cohort of 372 MVD
      operations carried out between 1982 and 2005 were reviewed, contact could be
      attempted with 319 patients. Questionnaires assessing the patient's perception of
      outcome returned by 266 patients (71%). statistical analysis of the data was
      carried out using a cox proportional-hazard regression analysis. Anticipated
      outcome measures: Time to pain recurrence; predictive value of imaging, operative
      findings and complications; patients' satisfaction, and outcome of revision MVD.
      RESULTS: Complete pain relief (off medication) achieved in 71% of patients at 10
      years. Overall 84% of responders to questionnaires expressed satisfaction with
      the operative outcome, the mean duration of TGN was 80 months and mean post
      operative follow-up of 7 years. No mortality reported in this series. CONCLUSION:
      This is a large review of MVD, which confirms the long-term effectiveness of the
      procedure, and uniquely reflects patient's perception of the operation.
      Predictors of favourable outcome were shorter preoperative duration of TGN, older
      age at time of MVD, typical features, and vascular compression; moreover,
      complications, and previous neurodestructive procedures did not show significant
      effect on long-term pain relief. Satisfaction with MVD was exclusively related to
      long-term pain relief without medications.

PMID- 20158349
TI  - The operative findings in re-do microvascular decompression for recurrent
      trigeminal neuralgia.
AB  - BACKGROUND: Re-do microvascular decompression (MVD) of the trigeminal nerve
      occasionally becomes necessary following recurrence of symptoms after a previous
      MVD. The indications include failure or contraindication of less invasive
      treatment options such as medication or trigeminal nerve lesioning and when
      supported by vascular compression on brain MRI scans. PURPOSE: To report on our
      findings following re-do MVD in the National Hospital for Neurology and
      Neurosurgery, Queen Square London from July 1995 to July 2008. METHODS: Case note
      review of all patients who underwent re-do MVD for the above reasons in the
      senior author's series in the above institution and stated period. The parameters
      of study interest were pre-operative MRI features, operative findings, and
      complete pain-free period with regards to the first and re-do MVD. RESULTS: Data
      analysis showed that 6 underwent a re-do MVD. Neurovascular conflict was
      confirmed in 5 cases (83.3%) involving the superior cerebellar artery and
      anterior inferior cerebellar artery in 2 cases each (33.3%) and ectatic basilar
      artery in 1 case (16.6%). Arachnoid adhesions around the previous teflon felt
      were also found in 5 cases (83.3%) mostly in association with other findings. Neo
      arachnoid cyst formation in the corresponding cerebello-pontine angle, was an
      unexpected finding in 2 cases (33.3%), though of uncertain significance.
      CONCLUSION: Redo MVD should be considered as a safe and effective treatment
      option in recurrent trigeminal neuralgia, which fails to respond to non-surgical
      means.

PMID- 20158350
TI  - Giant pituitary adenomas--an enigma revisited. Microsurgical treatment strategies
      and outcome in a series of 250 patients.
AB  - BACKGROUND: Giant pituitary adenomas (> 4 cm) are a surgical challenge. We
      present our experiences in surgical management of these tumors in a series of 250
      patients. METHODS: Two hundred and fifty patients with giant pituitary adenomas
      were managed surgically at our center over last 13 years. Majority (92%) of
      patients presented with visual deterioration. Non-functioning tumors were found
      in 136 patients (54.3%). Among functioning adenomas, 63 patients (25.4%) had
      prolactinomas and 45 patients (18%) had GH-secreting adenomas; while 3 patients
      each had LH and ACTH- secreting adenomas. The maximum tumor diameter varied from
      4 to 10.5 cm, with mean diameter of 5.4 cm. The factors determining choice of
      operative approach and surgical outcomes in these tumors were analyzed. RESULTS:
      Overall, 273 surgical procedures were performed in 250 patients. Of these, 110
      were transsphenoidal, while 163 were transcranial approaches. A single surgical
      procedure was performed in 227 patients (89.2%). 23 patients (9.2%) underwent re
      exploration either because of postoperative apoplexy or residual tumor. Overall,
      near total (>90%) tumor excision could be achieved in 74%, with improved vision
      in 53% and good outcome in 75% patients. The mortality and morbidity were 4.4%
      and 14%, respectively. CONCLUSIONS: The main goal of surgical treatment of giant
      pituitary adenoma is maximum possible tumor extirpation with minimal side
      effects, which can be achieved by careful preoperative planning of operative
      approach, based on directions of tumor extensions and invasiveness. Maximal
      surgical removal of giant adenomas offers best chances to control tumor growth
      when followed with adjuvant medical and radiation therapies.

PMID- 20158351
TI  - Does drill-induced noise have an impact on sensorineural hearing during
      craniotomy procedure?
AB  - OBJECTIVE: It is well known that exposure to noise can lead to hearing loss.
      Craniotomy drills have significant noise and vibration. Since a noise induced by
      the drill during craniotomy is thought to be one of the causes, we examined its
      effect on the sensorineural hearing in this study. METHODS: Thirty-nine patients
      who had undergone craniotomy operations served as the basis for this study
      between Jul. 2007 and Dec. 2008. Standard pure-tone audiometry (PTA) and speech
      recognition thresholds (SRT) were calculated for all subjects before, one week
      and 1 year after craniotomy. RESULTS: Statistically significant differences were
      not observed at the lower and middle frequencies (0.25-2 kHz), however,
      differences in the hearing thresholds at higher frequencies (4-6 kHz) were
      statistically significant before and after craniotomy. Mean pure-tone thresholds
      obtained was significantly more in older subjects when compared to young
      patients. Moreover, the correlation between increased number of burr holes and
      sensorineural hearing loss (SNHL) was statistically significant. CONCLUSIONS: We
      conclude that drill-generated noise during craniotomy has been incriminated as a
      cause of SNHL. Possible noise disturbance to the inner ear can only be avoided by
      minimizing the number of burr holes and the duration of harmful noise exposure to
      the cochlear structures.

PMID- 20158352
TI  - The clinical value of early postoperative MRI after lumbar spine surgery.
AB  - INTRODUCTION: MRI scanning has historically been considered difficult to
      interpret in the early period following lumbar spine surgery, and hence of
      limited value. We investigate the hypothesis that MRI scanning within 6 weeks of
      lumbar spine surgery cannot accurately diagnose neural compression in symptomatic
      patients, and define the utility of postoperative MRI in this context. METHODS: A
      series of 32 consecutive patients had early postoperative MRI following lumbar
      discectomy or laminectomy for continued, worsening or new symptoms of neural
      compression. The neuroradiologists' reports were evaluated for the reported
      presence of neural compression and confidence level (low, medium, high). These
      MRI findings were then compared to the patients' subsequent course and findings
      of any surgery performed. RESULTS: Twenty of 29 scans (69%) were confidently
      predictive of the correct treatment pathway (reoperation with positive finding or
      conservative treatment with a good outcome) whereas 3/3 (100%) patients who had
      conservative management despite the MRI confidently suggesting compression had
      poor outcome. The MRI is highly likely to influence management: 11/14 (79%)
      patients with scans suggesting neural compression had revision surgery and 18/18
      (100%) patients with no neural compression on MRI were managed conservatively.
      CONCLUSIONS: Our data suggest that early MRI scanning after lumbar laminectomy or
      discectomy accurately detects neural compression at the surgery site in patients
      with continued or worsening symptoms.

PMID- 20158353
TI  - The use of a reconstituted collagen foil dura mater substitute in paediatric
      neurosurgical procedures--experience in 47 patients.
AB  - BACKGROUND: CSF leakage is a common complication of neurosurgical procedures,
      with defective dural suture thought to be the most frequent cause. We report our
      experience with a new collagen foil (TissuDura, Baxter Healthcare SA,
      Switzerland) utilized as dural substitute in paediatric neurosurgical procedures.
      METHODS: TissuDura was used in children consecutively operated on at the
      department of paediatric neurosurgery, Catholic University, Rome, from March 2004
      to August 2007. Children underwent surgical procedures in supratentorial,
      infratentorial and spinal compartments. In supratentorial and spinal procedures,
      the dural graft was used according to the overlay technique. In the posterior
      fossa procedures, the underlay technique was used. RESULTS: Forty-seven patients
      received TissuDura during surgery. Thirty-one patients underwent surgery for the
      removal of posterior fossa tumours, nine for supratentorial tumours and seven for
      spinal dysraphisms. No CSF leakage was observed following the use of TissuDura in
      supratentorial procedures. Two post-operative CSF leaks occurred in patients who
      had undergone spinal surgery. No post-operative hydrocephalus was noted in these
      two surgery groups. Three cases of CSF leakage occurred in patients who had
      undergone posterior cranial fossa surgery. All 3 cases had an associated
      supratentorial ventricular dilation present prior to the removal of the tumour
      (one case) or occurring after the tumour excision (two cases). No clinically
      evident adverse reactions directly related to TissuDura were observed.
      CONCLUSIONS: The main advantages of TissuDura were its apparent ability to
      prevent CSF leakage when utilized in a specific subset of patients, and the
      absence of reactions or postoperative infections.

PMID- 20158354
TI  - Meningioma recurrence: the efficacy and cost-effectiveness of current screening.
AB  - Scanning of post-operative meningioma patients to detect tumour recurrence is
      common practice. There are however no guidelines for how often this should be
      performed for meningiomas of differing Simpson Grades of surgical removal and
      World Health Organisation (WHO) histological grades. A literature search reveals
      no studies investigating its role in post-operative care. The objective of this
      study was to determine current post-operative scanning use, in particular its
      timing and frequency in relation to meningioma recurrence rate. We performed a
      retrospective analysis of the surgical records of patients that underwent
      meningioma excision between 1998 and 2003 in Addenbrookes Hospital, and their
      follow-up scans up to 9 years post-surgery. Age at surgery, Simpson grade of
      surgical removal, tumour location, WHO histological grade, post-surgical
      radiotherapy, dates of meningioma recurrences, and dates of post-operative CT and
      MRI scans up to present, were recorded for each patient. A total of 283 records
      were analysed. Using logistic regression we found that WHO grade and post
      surgical radiotherapy were the strongest predictors of meningioma recurrence. We
      found that timing and frequency of scans between patients of the same stage and
      grade is highly variable. Data suggests that the role for regular short term post
      operative scanning of WHO grade 1 meningioma patients, a group that form the bulk
      of meningioma patients, is limited, and should only be performed in select,
      clinically indicated cases. A time and cost analysis reveals that significant
      savings can be made by adopting this policy. Data from a greater number of
      patients with WHO grade 2 and 3 meningiomas needs to analysed before definite
      conclusions can be made about the regularity of post-operative scanning in these
      patients. Our audit study has revealed an opportunity for significant monetary
      and time savings to be made without any compromise of patient care.

PMID- 20158355
TI  - Effects of cerebral microvascular endothelial cells and vascular endothelial
      growth factor on the proliferation and differentiation of NSCs: a comparative
      study.
AB  - In adult mammalian brain, microvessels may produce a special microenvironment and
      then influence the characteristics of neural stem cells (NSCs). This work aims to
      compare the effects of cerebral microvascular endothelial cells (CMECs) and
      vascular endothelial growth factor (VEGF) on the behaviors of NSCs. An in vitro
      model with co-cultured CMECs and NSCs was established by using transwell co
      culture system. The expression of nestin and NF in the early stage of the co
      culture, and NF in the later stage were explored by immunostaining. Results
      demonstrate that both CMECs and VEGF stimulate the proliferation of NSCs and
      inhibit the differentiation. After removing CMECs or VEGF from the co-culture
      system, a further culture in medium for the differentiation of NSCs was
      performed. The percentage of NF-positive cells in the CMECs co-culture group is
      the highest, suggesting the improved neuronal differentiation of NSCs by CMECs.

PMID- 20158356
TI  - Augmented reality neurosurgical planning and navigation for surgical excision of
      parasagittal, falcine and convexity meningiomas.
AB  - OBJECTIVE: To assess the utility of pre-operative 3-dimension (3D) visualisation
      and surgical planning with the Dextroscope in combination with the use of DEX-Ray
      a novel augmented reality surgical navigation platform for resection of
      meningiomas in the falcine, convexity and parasagittal regions. METHODS AND
      RESULTS: Magnetic resonance imaging (MRI) and magnetic resonance venogram (MRV)
      images of the patients were reconstructed in 3D using the Dextroscope
      workstation. Using a variety of available tools, we were able to view the tumour
      in various surgical angles and appreciate the intricate relationship of the
      tumour with respect to the surrounding structures and venous anatomy. Critical
      draining veins both superficial and deep to the tumour were well visualised. By
      varying the transparency of the overlying scalp and bone we were able to
      preoperatively determine the ideal size of our scalp flap and bone window for
      surgical approach. The Dextroscope enabled us to simulate surgical opening and
      various trajectories of approach while the DexRay virtual reality navigation
      system enabled the transfer of the Dextroscope 3D planning data into the
      operating by displaying it in real-time video-augmented mode which further
      enhanced the appreciation of the tumour's location in 3D space. Four patients
      underwent total excision of their meningioma while one patient had near total
      excision with a small residual remnant left behind at the medial third of the
      superior sagittal sinus. All 5 patients had good neurological recovery post
      operatively. CONCLUSION: The use of the Dextroscope for pre-operative surgical
      planning allows for appreciation of complex anatomical relationships in 3D. This
      appreciation is further translated for use during surgical navigation utilizing
      the DEX-Ray platform that provided us with the superior advantage of allowing
      fast and accurate surgical resection confidently.

PMID- 20158357
TI  - Placement of silicone sheeting at decompressive craniectomy to prevent adhesions
      at cranioplasty.
AB  - Adhesion formation between dura mater and cortex, and the overlying temporalis
      muscle and galea following decompressive craniectomy, can make subsequent
      cranioplasty difficult and adds to the risks of the procedure. We describe the
      implantation of sterile silicone sheeting at decompressive craniectomy to prevent
      adhesion formation and facilitate subsequent cranioplasty, potentially reducing
      surgical time, improving outcome and reducing risk.

PMID- 20158358
TI  - Intra-operative recurrent laryngeal nerve stimulation during anterior cervical
      discectomy: a simple and effective technique.
AB  - Recurrent laryngeal nerve (RLN) palsy is a recognised complication of anterior
      cervical discectomy (ACD) surgery. We report our experience of intra-operative
      neuromonitoring using RLN stimulation in 19 patients undergoing ACD surgery. This
      simple and safe technique has the potential to reduce the incidence of RLN palsy
      in this patient group.

PMID- 20158359
TI  - Sinus barotrauma leading to extradural muco-pneumocephalus.
AB  - An amateur scuba (Self Contained Underwater Breathing Apparatus) diver
      experienced an acute frontal headache following a low-depth dive. After 12 hours
      of worsening and unremitting headache, CT and MRI imaging were performed; these
      revealed gas and mucous in the frontal sinus and extradural space. This appears
      to be the first case of MRI-documented barotrauma of the frontal and ethmoidal
      sinuses resulting in extradural pneumo- and muco-cephalus.

PMID- 20158360
TI  - Spontaneous subarachnoid haemorrhage due to acoustic neurinoma. Case report and
      review of the literature.
AB  - Subarachnoid haemorrhage (SAH) of the posterior fossa in cases of acoustic
      neurinoma is very rare. The authors present the clinical, neuroradiological and
      histological findings of an acoustic neurinoma presenting with SAH. The
      literature regarding this subject is reviewed and the pathogenesis of haemorrhage
      from neurinoma is discussed.

PMID- 20158361
TI  - Primary intraosseus cavernous hemangioma of the skull base.
AB  - Primary intraosseous cavernous hemangioma (PICH) of the skull is rare. We present
      a case of 11-year-old boy with PICH of the sphenoid bone. The Computed Tomogram
      showed a classical sunburst appearance. Safe excision as much as possible was
      attempted after embolization. The child however, succumbed to postoperative
      infection. The preferred treatment is complete tumor removal with normal bony
      margins. However, this may not be possible in extensive skull base involvement.
      Preoperative embolisation can reduce intraoperative blood loss. Radiotherapy may
      be added where complete excision is not possible.

PMID- 20158364
TI  - Time for perceptions and prescribing to change?

PMID- 20158365
TI  - Management of arteriovenous malformations (AVMs) presenting with intracranial
      haemorrhage: the role of subacute resection.

PMID- 20158366
TI  - Equipoise and randomisation in surgery.
AB  - In science, when a prevailing model does not fit reality the model is changed to
      fit better. The process is often accompanied by noisy attempts from some quarters
      to change reality to fit the model. So it is with randomised trials in surgery,
      the letter of Helmy et al. being an example. The randomised model used in drug
      trials does not fit surgery well for several well-rehearsed reasons, a
      significant point of poor fit being the question of equipoise.

PMID- 20158370
TI  - Toxicity of the antimalarial artemisinin and its dervatives.
AB  - As long as no effective malaria vaccine is available, chemotherapy belongs to the
      most important weapons fighting malaria. One of the most promising new drug
      developments is the sesquiterpene artemisinin (ARS) and its derivatives, e.g.,
      artemether, arteether, and sodium artesunate. Large clinical studies and meta
      analyses did not show serious side effects, although proper monitoring of adverse
      effects in developing countries might not be a trivial task. There is a paucity
      of large-scale clinical trials suitable to detect rare but significant toxicity.
      Therefore, a final and definitive statement on the safety of artemisinins still
      cannot be made. In contrast, animal experiments show considerable toxicity upon
      application of artemisinins. In the present review, the authors give a
      comprehensive overview on toxicity studies in cell culture and in animals (mice,
      rats, rabbits, dogs, monkeys) as well as on toxicity reported in human clinical
      trials. The authors emphasize the current knowledge on neurotoxicity,
      embryotoxicity, genotoxicity, hemato- and immunotoxicity, cardiotoxicity,
      nephrotoxicity, and allergic reactions. The lesson learned from animal and human
      studies is that long-term availability rather than short-term peak concentrations
      of artemisinins cause toxicity. Rapid elimination of artemisinins after oral
      intake represents a relatively safe route of administration compared to delayed
      drug release after intramuscular (i.m.) injection. This explains why considerable
      toxicities were found in the majority of animal experiments, but not in human
      studies. In addition, there are drug-related differences, i.e., intramuscular
      application of artemether or arteether, but not to artesunate, which is safe and
      gives good profiles after i.m. administration in severe malaria. Although there
      is no need to increase doses of artemisinins for uncomplicated malaria, this has
      to be taken into account for cerebellar involvement in severe malaria. It might
      also be important in determining dose limitations for treatment of other diseases
      such as cancer.

PMID- 20158371
TI  - Validation of the International Classification of Functioning Disability and
      Health framework using multidimensional item response modeling.
AB  - PURPOSE: To examine the construct validity of the International Classification of
      Functioning Disability and Health (ICF) framework using multidimensional item
      response modelling and data collected in different regions from patients with
      five chronic health conditions. We assume that the ICF components should
      represent statistically called dimensions that are distinct although related.
      METHOD: Retrospective validation study using the ICF Core Sets from a convenience
      sample of patients in an international multicentre, cross-sectional database
      obtained in different rehabilitation centres. Health professionals working in 89
      rehabilitation centres in 32 countries collected data from 3227 rehabilitation
      patients using the respective ICF Core Sets. Patients included had one of the
      following health conditions: low back pain (LBP), rheumatoid arthritis (RA),
      osteoarthritis (OA), obesity (OB) or post-stroke. Data from questions regarding a
      patient's functioning based on body structures and functions, activities,
      participation along the ICF Core Sets were analysed with multidimensional item
      response modelling. RESULTS: The multidimensional models fit the data better than
      a model with few or no specifications regarding an underlying framework. For
      example, a model separating four dimensions 'body structures', 'body functions',
      'activities' and 'participation' fits the data better than a model
      differentiating between 'body functions and structures' and 'activities and
      participation'. The ICF framework with its components represents underlying
      statistically called dimensions. CONCLUSION: The results of this study support
      the construct validity of the functioning part of the ICF. The distinct
      dimensions may facilitate the alignment of ICF components with other measures
      used clinically and in research. Based on our results it is justifiable to
      construct instruments integrating ICF categories within components.

PMID- 20158372
TI  - Are neck pain scales and questionnaires compatible with the international
      classification of functioning, disability and health? A systematic review.
AB  - PURPOSE: To identify neck-pain-specific questionnaires and scales that measure
      functioning and disability and assess whether their contents are comparable to
      the international classification of functioning, disability and health (ICF).
      METHODS: A systematic search was conducted in LILACS, MEDLINE, CINAHL, and
      SPORTSDISCUS databases, identifying questionnaires and scales used to assess neck
      related functioning and disability from 1966 to November 2007. Each item of each
      scale or questionnaire was extracted and classified according to the ICF
      categories. RESULTS: The databases yielded a total of 888 articles, of which
      seven questionnaires were identified and included in the review. A total of 74
      items were analyzed, 27 linked to body function, 46 to activities and
      participation, 1 to environmental factors, and 5 to non-classified items. While
      the pain disability index tends to focus on limitations to body functions, the
      functional rating index and the Copenhagen neck functional disability scale
      appear to be limited to measuring activity. Three questionnaires (the neck
      Bournemouth Questionnaire, the neck disability index, and the neck pain and
      disability scale) have demonstrated a well-balanced distribution of items across
      the ICF components. CONCLUSION: Most identified questionnaires reflect
      limitations or restrictions in one component only. These results provide valuable
      information on the content quality of these questionnaires for health-care
      providers and researchers.

PMID- 20158373
TI  - Employment maintenance and the factors that impact it after vocational
      rehabilitation and return to work.
AB  - PURPOSE: To determine post-return-to-work disability and functioning amongst
      occupationally injured workers and to test the extent to which demographic and
      other variables relate to employment maintenance. In addition, the project sought
      to document what workers believe determined their work continuation. METHOD: Semi
      structured in-depth interviews were conducted to inquire about participant's (N =
      150) post-vocational rehabilitation return-to-work experiences. Results were
      interpreted using the health and health-related domains from the International
      Classification of Functioning, Disability and Health. RESULTS: Although most
      participants were working at the time of interview, almost all were experiencing
      functional- or activity-based restrictions. Factors differentiating those
      employed from those not, were largely contextual and included relationships with
      supervisors, economic climate, and working conditions. CONCLUSIONS: The findings
      stress the importance of considering environmental strains when planning return
      to work and indicate ways to assist workers to achieve return-to-work success.

PMID- 20158374
TI  - Physical disability, recent illnesses and health self-assessment in a population
      based study in Sao Paulo, Brazil.
AB  - OBJECTIVES: To investigate health self-assessment and to estimate the prevalence
      of chronic diseases and recent illnesses in people with and without physical
      disabilities (PD) in the state of Sao Paulo, southeastern Brazil. STUDY DESIGN: A
      cross-sectional study comprising two population-based health surveys conducted in
      2002 and 2003. METHODS: A total of 8317 persons (165 with PD) were interviewed in
      the two studies. Variables concerning to health self-assessment; chronic disease
      and recent illness were compared in the people with and without PD. Negative
      binomial regression was used in the analysis. RESULTS: Subjects with PD more
      often assessed their health as poor/very poor compared to non-disabled ones. They
      reported more illnesses in the 15 days prior to interview as well as more chronic
      diseases (skin conditions, anaemia, chronic kidney disease, stroke,
      depression/anxiety, migraine/headache, pulmonary diseases, hypertension,
      diabetes, arthritis/arthrosis/rheumatic conditions and heart disease). This
      higher disease prevalence can be either attributed to disability itself or be
      associated to gender, age and schooling. CONCLUSIONS: Subjects with PD had more
      recent illnesses and chronic diseases and poorer health self-assessment than non
      disabled ones. Age, gender, schooling and disability have individual roles in
      disease development among disabled people.

PMID- 20158375
TI  - Development and initial validation of the Children Participation Questionnaire
      (CPQ).
AB  - PURPOSE: To develop and test the psychometric properties of a parent-reported
      questionnaire measuring participation of preschool children (Children
      Participation Questionnaire; CPQ) aged 4-6 years in their everyday activities.
      METHODS: Reliability was tested by Cronbach's alpha and by test-retest. Construct
      validity was computed by known group differences analysis. Convergent and
      divergent validities were calculated by correlation with the Vineland Adaptive
      Behaviour Scale (VABS). Two hundred thirty-one children with mild to moderate
      developmental disabilities (mean age 5.16 +/- 0.66 years old) were compared to
      249 children without disability (mean age 5.13 +/- 0.72 years old). RESULTS: The
      CPQ has good internal reliability. Cronbach's alpha for the participation
      measures ranged between 0.79 and 0.90, indicating good homogeneity. The temporal
      stability of the CPQ was supported with intra-class correlations ranging from
      0.71 to 1.00. Significant differences were found between children with and
      without disabilities in all the CPQ measures. The CPQ could also differentiate
      between age groups and groups of varying socio-economic status. Convergent and
      divergent validity were supported. CONCLUSIONS: The CPQ has demonstrated good
      psychometric properties and can be used as a reliable and valid measure to assess
      children's participation at the age of 4-6 years.

PMID- 20158376
TI  - Racial disparities in stroke functional outcomes upon discharge from inpatient
      rehabilitation facilities.
AB  - PURPOSE: Analyse racial disparities in clinical outcomes after stroke in
      inpatient rehabilitation facilities (IRF). METHODS: Analyses based on data from a
      multi-center prospective observational cohort study on inpatient stroke
      rehabilitation in six IRFs from across the United States. Multivariate models
      examined racial disparities in functional outcomes upon discharge, taking into
      account patient characteristics and detailed information on processes of care.
      RESULTS: In the moderate stroke group (N = 397), functional scores on admission
      were not significantly different between African-Americans and whites. In the
      severe stroke group (N = 335), whites showed significantly lower functional
      scores at admission [Functional Independence Measurement, (FIM)], mean scores, 44
      versus 49 for African-Americans, p < 0.001). Multivariate analyses predicting
      discharge motor FIM score found no significant differences between African
      American and white stroke patients (p = 0.2194 and p = 0.3547 in the moderate and
      severe stroke group, respectively). CONCLUSION: Controlling for patient
      characteristics, therapy intensity and processes of care results in non
      significant differences between African-Americans and whites in motor FIM scores
      upon discharge. The absence of significant differences in recovery while patients
      were on the rehabilitation unit suggests that racial disparities in long-term
      functional recovery after stroke are likely to have originated before or after
      the inpatient rehabilitation stay.

PMID- 20158377
TI  - Neuropathology of a fatal case of posterior reversible encephalopathy syndrome.
AB  - The pathology of posterior reversible encephalopathy syndrome (PRES) is
      undefined, since it is rarely fatal and is biopsied in only exceptional
      circumstances. We describe rapidly progressive PRES following stem cell
      transplant for acute lymphoblastic leukemia. After development of altered mental
      status, this 8-year-old girl had T2 prolongation of the white matter in a
      posterior-dominant distribution, eventually developing cerebellar edema,
      hemorrhage, hydrocephalus, and herniation. Despite surgical and medical
      management, she died 36 hours later. At autopsy, the occipital and cerebellar
      white matter and focal occipital cortical gray matter showed a spectrum of
      microvascular changes, including dilated perivascular spaces containing
      proteinaceous exudates and macrophages, as well as fibrinoid necrosis and acute
      hemorrhage, in a distribution corresponding to the neuroimaging abnormalities and
      reminiscent of those seen in patients with acute hypertensive encephalopathy. Of
      note, similar microvascular changes were not seen in the kidney or other systemic
      sites. Thus, the findings indicate a brain-specific microvascular compromise as
      the substrate of PRES, at least in the rare instance of cases progressing to
      fatal outcome.

PMID- 20158378
TI  - Supernumerary intestinal muscle coat in a patient with Hirschsprung disease/Mowat
      Wilson syndrome.
AB  - We present the 1st case report of an additional enteric smooth muscle layer in a
      patient with Mowat-Wilson syndrome and Hirschsprung disease. After resection of
      the aganglionic colon at the age of 5 months, our patient initially suffered from
      intermittent constipation, and subsequently by the age of 5 years, he developed
      ongoing diarrhea requiring medical treatment for more than a decade. Although the
      exact mechanism of abnormal gut motility in this case is unknown, we postulate
      that the supernumerary muscle and its associated neural plexus may be responsible
      for the patient's unusual late complication in treated Hirschsprung disease.

PMID- 20158380
TI  - Hyperthermia induces platelet apoptosis and glycoprotein Ibalpha ectodomain
      shedding.
AB  - Hemorrhage is a significant pathological feature of some fever or hyperthermia
      related diseases, such as dengue fever and heatstroke. Although the mechanisms of
      hemorrhage in these diseases are thought to be complex, whether there is an
      association between hemorrhage and hyperthermia or fever remains unclear.
      Platelets play a central role in maintaining integrity of endothelium and
      biological hemostasis. To explore the effect of hyperthermia on platelet
      physiology, platelet-rich plasma or washed platelets were incubated at
      hypothermia (22 degrees C), normothermia (37 degrees C) or hyperthermia (40 and
      42 degrees C) for 1 or 2 hours. ADP and alpha-thrombin induced platelet
      aggregations were obviously reduced in platelets incubated at hyperthermia.
      Hyperthermia induced apoptotic events in platelets, including depolarization of
      mitochondrial inner transmembrane potential, caspase-3 dependent gelsolin
      cleavage and phosphatidylserine exposure. Furthermore, hyperthermia incurred
      platelet glycoprotein Ibalpha ectodomain shedding. Thus, these data suggest that
      hyperthermia induces platelet apoptosis and dysfunction. These findings have
      important implications for the pathogenesis of hemorrhage in fever or
      hyperthermia-related diseases, and also suggest that attention should be paid to
      platelet apoptosis under relatively high temperature conditions.

PMID- 20158379
TI  - The effect of epidermal growth factor in the injured brain after trauma in rats.
AB  - Epidermal growth factor (EGF) is a known mitogen for neural stem and progenitor
      cells (NS/NPCs) in the central nervous system (CNS). In vitro, EGF maintains
      NS/NPCs in the proliferative state, whereas in the normal rodent brain it
      promotes their proliferation and migration in the subventricular zone (SVZ).
      Additionally, EGF administration can augment neuronal replacement in the ischemic
      injured adult striatum. Recently we found that the SVZ and the hippocampus
      display an injury-induced proliferative response following traumatic brain injury
      (TBI) that is linked to increased EGF expression. As adult neurogenesis is
      associated with cognitive function, we hypothesized that post-TBI administration
      of EGF could affect neurogenesis and cognitive recovery. Adult rats were
      intraventricularly infused with EGF or vehicle for 7 days following TBI. 5-Bromo
      2-deoxyuridine (BrdU) was administered to label proliferating cells and the
      animals were sacrificed at 1 or 4 weeks post-injury. Using immunohistochemistry
      and stereology, we found that at 1 week post-injury, compared to vehicle-infused
      animals EGF-infused animals had significantly more BrdU-positive cells in the SVZ
      and hippocampus concomitant with enhanced EGF receptor expression. At 4 weeks
      post-injury, the number of BrdU-positive cells in the hippocampus was similar in
      both groups, suggesting that EGF does not support long-term survival of newly
      generated cells. Furthermore, we found that the EGF-induced proliferative
      population differentiated preferentially toward astroglial phenotype.
      Nevertheless, animals treated with EGF showed significant improvement in
      cognitive function, which was accompanied by reduced hippocampal neuronal cell
      loss. Collectively, the data from this study demonstrate that EGF exerts a
      neuroprotective rather than neurogenic effect in protecting the brain from
      injury.

PMID- 20158381
TI  - Platelet concentrates transfusion in cardiac surgery in relation to preoperative
      point-of-care assessment of platelet adhesion and aggregation.
AB  - Platelet dysfunction is an important cause of bleeding early after cardiac
      surgery. Whole-blood multiple electrode aggregometry (MEA), investigating the
      adhesion and aggregation of activated platelets onto metal electrodes, has shown
      correlations with platelet concentrates transfusion in this setting. Platelet
      activity in vivo is dependent on shear stress, an aspect that cannot be
      investigated with MEA, but with the cone and plate(let) analyzer (CPA) Impact-R
      that measures the interaction of platelets and von Willebrand factor (vWF) in
      whole blood under shear. We hypothesized that preoperative CPA may show better
      correlation with platelet concentrates transfusion post-cardiac surgery than MEA,
      since it is dependent on both platelet activity and platelet interaction with vWF
      multimers. Blood was obtained preoperatively from 30 patients undergoing aorto
      coronary bypass (ACB) and 20 patients with aortic valve (AV) surgery. MEA was
      performed in hirudin-anticoagulated blood. The Impact-R analyses were performed
      in blood anticoagulated with hirudin, heparin or the standard anticoagulant
      citrate. For the light microscopy images obtained, the parameter surface coverage
      (SC) was calculated. Preoperative Impact-R results were abnormally decreased in
      AV patients and significantly lower than in ACB patients. For the Impact-R
      analysis performed in citrated blood, no correlation with platelet concentrates
      transfusion was observed. In contrast, MEA was comparable between the groups and
      correlated significantly with intraoperative platelet concentrates transfusion in
      both groups (rho between -0.47 and -0.62, p < 0.05). Multiple electrode
      aggregometry appeared more useful and easier to apply than CPA for preoperatively
      identifying patients with platelet concentrates transfusion in cardiac surgery.

PMID- 20158382
TI  - Curcumin inhibits GPVI-mediated platelet activation by interfering with the
      kinase activity of Syk and the subsequent activation of PLCgamma2.
AB  - Turmeric (Curcuma longa), a herbal remedy and culinary spice, has been used in
      traditional Indian culture for millennia. An active ingredient found in turmeric
      is curcumin (diferuloylmethane). In the current study, we investigated the
      antiplatelet properties of this naturally occurring compound. Curcumin inhibited
      human platelet aggregation and dense granule secretion induced by GPVI agonist
      convulxin in a concentration-dependent manner. At 50 microM, it effectively
      inhibited the maximal extent of aggregation and dense granule secretion to as
      much as 75%. It also dramatically inhibited the activation-dependent tyrosine
      phosphorylation of Y753 and Y759 on PLCgamma2, but did not affect the
      phosphorylation of Y145 residue on the cytosolic adaptor protein SLP-76.
      Interestingly, curcumin had no significant effect on the phosphorylation of
      Y525/Y526 present on the activation loop of Syk (spleen tyrosine kinase), but had
      a significant inhibitory effect on in vitro Syk kinase activity. Moreover, the
      inhibitory action of curcumin is not due to an inhibition of thromboxane
      generation because all our studies were performed using aspirin-treated
      platelets. We conclude that curcumin inhibits platelet activation induced by GPVI
      agonists through interfering with the kinase activity of Syk and the subsequent
      activation of PLCgamma2.

PMID- 20158383
TI  - Exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin and tetraethyl lead affects
      lung mitochondria bioenergetics.
AB  - Environmental pollutants such as TCDD and tetraethyl lead are extremely toxic and
      related with pulmonary disease development. Lung mitochondria are primary
      cellular targets for dioxins exposure-induced toxicity. TCDD showed a delay in
      the repolarization after a phosphorylative cycle and a decrease on state 3
      respiration, suggesting alterations at the phosphorylative system level. The
      ATPase activity showed no differences between control and lung mitochondria
      incubated with TCDD, implying alterations in other components of the
      phosphorylative system. Tetraethyl lead also showed a delay in the repolarization
      after a phosphorylative cycle and a decrease on RCR. These data suggest that lung
      mitochondria incubated with TCDD and tetraethyl lead showed impaired
      mitochondrial function, reflecting the loss of oxidative phosphorylation
      capacity.

PMID- 20158384
TI  - Mutagenicity of acrolein and acrolein-induced DNA adducts.
AB  - Acrolein mutagenicity relies on DNA adduct formation. Reaction of acrolein with
      deoxyguanosine generates alpha-hydroxy-1, N(2)-propano-2'-deoxyguanosine (alpha
      HOPdG) and gamma-hydroxy-1, N(2)-propano-2'-deoxyguanosine (gamma-HOPdG) adducts.
      These two DNA adducts behave differently in mutagenicity. gamma-HOPdG is the
      major DNA adduct and it can lead to interstrand DNA-DNA and DNA-peptide/protein
      cross-links, which may induce strong mutagenicity; however, gamma-HOPdG can be
      repaired by some DNA polymerases complex and lessen its mutagenic effects. alpha
      HOPdG is formed much less than gamma-HOPdG, but difficult to be repaired, which
      contributes to accumulation in vivo. Results of acrolein mutagenicity studies
      haven't been confirmed, which is mainly due to the conflicting mutagenicity data
      of the major acrolein adduct (gamma-HOPdG). The minor alpha-HOPdG is mutagenic in
      both in vitro and in vivo test systems. The role of alpha-HOPdG in acrolein
      mutagenicity needs further investigation. The inconsistent result of acrolein
      mutagenicity can be attributed, at least partially, to a variety of acrolein-DNA
      adducts formation and their repair in diverse detection systems. Recent results
      of detection of acrolein-DNA adduct in human lung tissues and analysis of P53
      mutation spectra in acrolein-treated cells may shed some light on mechanisms of
      acrolein mutagenicity. These aspects are covered in this mini review.

PMID- 20158386
TI  - Safety and toxicological evaluation of a novel anti-obesity formulation LI85008F
      in animals.
AB  - LI85008F is a novel synergistic composition of Moringa oleifera, Murraya koenigi,
      and Curcuma longa. These herbs are well recognized and widely used in ayurvedic
      system of medicine for treating a variety of diseases and are also have been used
      for culinary purposes for thousands of years. LI85008F inhibits preadipocyte
      differentiation and potentiates lipid breakdown in mature adipocytes. In diet
      induced obese rats, LI85008F significantly reduced weight gain and improved serum
      adiponectin levels. These findings motivated the authors to determine the broad
      spectrum safety of LI85008F. Acute oral toxicity, acute dermal toxicity, primary
      skin irritation, primary eye irritation, and dose-dependent 28-day sub-acute
      toxicity studies were conducted. The acute oral LD50 of LI85008F was greater than
      5000 mg/kg in female SD rats and no changes in body weight or adverse effects
      were observed following necropsy. Acute dermal LD50 of LI85008F was greater than
      2000 mg/kg. LI85008F was classified as non-irritating to skin in a primary dermal
      irritation study conducted using New Zealand Albino rabbits. LI85008F caused
      minimal irritation to eyes in a primary eye irritation test conducted on New
      Zealand Albino rabbits. A dose-dependent 28-day sub-acute toxicity study
      demonstrated no significant changes in selected organ weights. Evaluations on
      hematology, clinical chemistry, and histopathology did not show any significant
      adverse changes. The NOAEL of LI85008F was found to be greater than 2500 mg/kg
      body weight. These results demonstrate the broad spectrum safety of LI85008F in
      animal models.

PMID- 20158385
TI  - Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose
      tissue microsomes.
AB  - The present study has been undertaken to examine whether exposure to
      benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound,
      influences the metabolism of fluoranthene (FLA), another PAH compound. Microsomes
      were isolated from the adipose tissue of mice that received 50 microg/kg BaP and
      incubated with FLA (3 microM) alone; FLA in combination with BaP at equimolar
      concentrations, and a control group that received nothing. Post-incubation,
      samples were extracted with ethyl acetate and analyzed for FLA metabolites by
      reverse-phase HPLC with fluorescence detection. The rate of FLA metabolism (pmol
      of metabolite/min/mg protein) was increased when microsomes from BaP-treated mice
      were exposed to FLA alone and FLA in combination with BaP, compared to controls.
      On the other hand, the difference in FLA metabolic rate between microsomes that
      were exposed to FLA + BaP was higher than the ones that received FLA. The
      microsomes from BaP-pre-treated mice produced a considerably higher proportion of
      FLA 2, 3-diol, and 2, 3 D FLA when microsomes were incubated with FLA. There were
      no differences in the FLA metabolite types formed when BaP-pre-treated mice were
      co-incubated with BaP and FLA than with FLA alone. The enhanced biotransformation
      of FLA as a result of prior and concomitant exposure to BaP may have implications
      for assessment of risks arising from human exposure to PAH mixtures.

PMID- 20158387
TI  - Enhanced fat consumption potentiates acrylamide-induced oxidative stress in
      epididymis and epididymal sperm and effect spermatogenesis in mice.
AB  - Acrylamide (ACR) and high contents of fat could be found co-existent in many
      foods processed by high temperature, such as deep-frying and roasting. This study
      investigated the effect of enhanced fat consumption on deficits of
      spermatogenesis induced by ACR, and explored potential mechanisms of oxidative
      damage involved in this pathology in mice. Results show that enhanced feeding of
      corn oil and pork fat on mice potentiated the decreases of spermatogonia along
      with mature sperms after treatment of ACR, and that spermatozoa quality is
      significantly reduced as a result of enhanced feeding of corn oil and pork fat on
      mice treated with ACR. Moreover, enhanced consumption of corn oil and pork fat
      potentiated the up-regulation of malondialdehyde (MDA) level in epididymal sperm
      and cauda epididymides, also up-regulated level of Protein carbonyls (PCOs) in
      cauda epididymides, of mice after treatment of ACR. Last, enhanced consumption of
      corn oil and pork fat potentiated the reduced activity of superoxide dismutases
      (SOD) in epididymal sperm, corpus, and cauda epididymides, also reduced activity
      of glutathione peroxidase (GPx) in cauda epididymides, of mice treated with ACR.
      These data suggest that enhanced feeding of corn oil and pork fat on mice
      potentiates ACR-induced oxidative stress in the epididymis and epididymal sperm
      and a subsequent effect on spermatogenesis.

PMID- 20158388
TI  - Increase in the prevalence of metabolic syndrome among workers according to age.
AB  - INTRODUCTION: Statistical information regarding the prevalence of metabolic
      syndrome among a wide age range of workers is insufficient. METHODS: A total of
      4278 men between the ages of 20 and 59 years participated in the study. Metabolic
      syndrome was diagnosed according to the International Diabetes Federation (IDF)
      and the National Cholesterol Education Program (NCEP) III criteria. RESULTS:
      Overall, the prevalences of metabolic syndrome according to the IDF and NCEPIII
      criteria were 13.6% and 14.8%, respectively. The prevalence of metabolic syndrome
      according to the IDF (NCEPIII) criteria among workers in their 20s, 30s, 40s, and
      50s were 4.8% (6.1%), 9.9% (12.2%), 18.4% (21.6%) and 25.8% (34.0%),
      respectively. A plot of the prevalence of metabolic syndrome according to the
      NCEPIII criteria versus age had a steep gradient and increased sharply for men in
      their 50s. In contrast, a plot of the prevalence of metabolic syndrome according
      to the IDF criteria versus age increased in a linear manner. CONCLUSION: The
      prevalence of metabolic syndrome increased among workers according to age, but
      the increasing trend and the absolute prevalence of metabolic syndrome differed
      according to the two sets of diagnostic criteria used in this study.

PMID- 20158389
TI  - Changes in bone health and skeletal-related events following implementation of a
      multidisciplinary consensus statement guiding surveillance and treatment of men
      undergoing androgen deprivation therapy for prostate cancer.
AB  - PURPOSE: Androgen deprivation therapy (ADT) is a cornerstone for inhibiting
      progression of prostate cancer (CAP) and improving survival. After previously
      establishing that men with CAP treated with ADT at our institution had
      significant skeletal morbidity, we evaluate the effectiveness of a
      multidisciplinary consensus statement (MCS) to improve outcomes. MATERIALS AND
      METHODS: We reviewed the records of men treated with ADT in our clinic. Only 38%
      of men had BMD studies, and 81% of those men had bone loss. Twenty-four percent
      of men had skeletal-related events (SREs). A minority of men were being treated
      for bone loss. We decided not to initiate therapy soon enough, and implemented an
      MCS to guide surveillance and treatment. RESULTS: Four years after implementing
      the MCS, half of the men were still being treated with ADT and the average
      treatment length doubled. Significantly more men were being screened, bone loss
      remained stable, and there was a trend towards decreased SREs. Significantly more
      men were being treated for bone loss. CONCLUSIONS: After implementing an MCS we
      show stable bone mineral density and a trend towards decreased SREs despite
      doubling of the treatment length. We document significant improvement in our
      practice pattern.

PMID- 20158390
TI  - The impact of irritative lower urinary tract symptoms on erectile dysfunction in
      aging Taiwanese males.
AB  - OBJECTIVE: This study assessed the possible associations between lower urinary
      tract symptoms (LUTS) and erectile dysfunction (ED) in aging Taiwanese males and
      investigated the impact of various aspects of LUTS on ED. METHODS: A free health
      screening for aging males (> or =40 years old) was conducted in Kaohsiung Medical
      University Hospital. All the subjects had completed clinical data and answered
      questionnaires. ED and LUTS were assessed by validated symptom scales: the
      International Index of Erectile Function-5 (IIEF-5) and the International
      Prostate Symptom Score (IPSS). RESULTS: A total of 339 eligible patients enrolled
      in this study with a mean age of 60.1 years old. In multiple logistic regression
      analysis, age and IPSS (p < 0.001 and p = 0.013, respectively) were significantly
      associated with ED after controlling other comorbidities. In a further age
      adjusted multiple regression analysis, our results showed that irritative
      symptoms (p = 0.042) have a more significant association with ED than the
      obstructive symptoms (p = 0.101). CONCLUSIONS: Our results indicate that age and
      LUTS are the two most independent risk factors for ED. Aging Taiwanese males with
      LUTS are at increasing risk for ED, especially for those with significant
      irritative symptoms.

PMID- 20158391
TI  - Interferon beta modulates endothelial damage in patients with cardiac persistence
      of human parvovirus b19 infection.
AB  - BACKGROUND: In a phase 1 study, we investigated whether interferon beta reduced
      endothelial damage in patients with cardiac persistence of human parvovirus B19
      (B19V) infection. METHODS AND RESULTS: In vitro, B19V infected cultivated
      endothelial cells (ECs), which led to a reduction in their viability (P = .007).
      Interferon beta suppressed B19V replication by 63% (P = .008) in ECs and
      increased their viability (P = .021). Circulating mature apoptotic ECs (CMAECs
      [CD45(-)CD146(+) cells expressing von Willebrand factor and annexin V]) and
      circulating progenitor cells (CPCs [CD34(+)KDR(+) cells]) were quantified by flow
      cytometry in 9 symptomatic patients with cardiac B19V infection before and after
      6 months of interferon beta therapy (16 MU) and were compared to levels in 9
      healthy control subjects. Endothelial dysfunction was measured using flow
      mediated dilatation of the forearm. Patients with B19V persistence had
      significantly higher (P = .04) levels of CMAECs than did control subjects, which
      normalized after treatment (mean +/- standard deviation, 0.06% +/-0.08% vs 0.01%
      +/- 0.006%; P = .008). Similar improvement was shown for flow-mediated dilatation
      (P = .04) in the treatment group only (P = .017 for the comparison with untreated
      patients with B19V persistence n = 5). There were significantly higher numbers of
      CPCs in patients with B19V persistence before therapy (mean +/- standard
      deviation, 0.04% +/- 0.05% vs 0.01% +/- 0.004%; P = .02; than in control
      subjects, which normalized after treatment (P = .03). CONCLUSION: Thus, we
      present (for the first time, to our knowledge) a modulation of virally induced
      chronic endothelial damage-specifically, EC apoptosis and endothelial
      regeneration.

PMID- 20158392
TI  - Mechanisms of immune evasion induced by a complex of dengue virus and preexisting
      enhancing antibodies.
AB  - We have found that dengue virus (DENV) not only uses preexisting enhancing
      antibodies to promote its entry into Fc receptor-bearing cells but also exploits
      enhancing antibodies for intracellular immune evasion through 2 mechanisms. In
      the first mechanism, entry of DENV-antibody complexes into human monocytic cells
      activates negative regulators, dihydroxyacetone kinase and autophagy-related 5
      autophagy-related 12, which then disrupt the retinoic acide incucible gene I and
      melanoma differentiation associated gene 5 signaling cascade and disable type 1
      interferon production, leading to suppression of interferon-mediated antiviral
      responses. In the second mechanism, the immune evasion was found to be mediated
      by the suppressive cytokine interleukin 10 (IL-10). High levels of IL-10
      activated expression of suppressor of cytokine signaling 3 gene, which
      subsequently inactivated the Janus kinase-signal transducer and activator of
      transcription pathway. Inhibition of IL-10 production by small interfering RNA
      down-regulated suppressor of cytokine signaling 3 gene expression, restored
      inducible nitric oxide synthase gene expression, and suppressed DENV replication.
      Importantly, we were able to demonstrate that these 2 loops of suppression
      occurred in patients with severe secondary dengue infection (dengue hemorrhagic
      fever) but not in patients with mild secondary dengue infection (dengue fever).

PMID- 20158393
TI  - Evidence in support of a role for anti-angiogenic factors in preterm prelabor
      rupture of membranes.
AB  - OBJECTIVE: Vaginal bleeding, placental abruption, and defective placentation are
      frequently observed in patients with preterm prelabor rupture of membranes
      (PROM). Recently, a role of vascular endothelial growth factor (VEGF) and its
      receptor, VEGF receptor (VEGFR)- 1 has been implicated in the mechanisms of
      membrane rupture. The purpose of this study was to determine whether the soluble
      form of VEGFR-1 and -2 concentrations in amniotic fluid (AF) change with preterm
      PROM, intra-amniotic infection/inflammation (IAI), or parturition. STUDY DESIGN:
      This cross-sectional study included 544 patients in the following groups: (1)
      midtrimester (MT) (n = 48); (2) preterm labor (PTL) leading to term delivery (n =
      143); (3) PTL resulting in preterm delivery with (n = 72) and without IAI (n =
      100); (4) preterm PROM with (n = 46) and without IAI (n = 42); (5) term in labor
      (n = 48); and (6) term not in labor (n = 45). The concentrations of sVEGFR-1 and
      sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic
      regression analysis were applied. RESULTS: (1) Preterm PROM (with and without
      IAI) had a lower median AF concentration of sVEGFR-1 than patients with PTL who
      delivered at term (p < 0.001 for each comparison); (2) A decrease in AFsVEGFR-1
      concentrations per each quartile was associated with PROM after adjusting for
      confounders (OR 1.8; 95%CI 1.4-2.3); (3) IAI, regardless of the membrane status,
      was not associated with a change in the median AF concentrations of sVEGFR-1 and
      sVEGFR-2 (p > 0.05 for each comparison); and (4) Spontaneous term and PTL did not
      change the median sVEGFR-1 and sVEGFR-2 concentrations (p > 0.05 for each
      comparison). CONCLUSION: (1) This is the first evidence that preterm PROM is
      associated with a lower AF concentration of sVEGFR-1 than patients with PTL
      intact membranes. These findings cannot be attributed to gestational age, labor,
      or IAI; and (2) AF concentrations of sVEGFR-2 did not change with preterm PROM,
      IAI, or labor at term and preterm.

PMID- 20158394
TI  - Serum and plasma determination of angiogenic and anti-angiogenic factors yield
      different results: the need for standardization in clinical practice.
AB  - OBJECTIVE: The importance of an anti-angiogenic state as a mechanism of disease
      in preeclampsia is now recognized. Assays for the determination of concentrations
      of soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2,
      placental growth factor (PlGF) and soluble endoglin (sEng) have been developed
      for research and clinical laboratories. A key question is whether these factors
      should be measured in plasma or serum. The purpose of this study was to determine
      if there are differences in the concentrations of these analytes between plasma
      and serum in normal pregnancy and in preeclampsia. METHODS: Samples of maternal
      blood were obtained by venipuncture and collected in EDTA (lavender top) and
      serum collection tubes (red top). A standard laboratory procedure was implemented
      for the centrifugation, aliquoting and storage of samples. Plasma and serum from
      70 women with normal pregnancies and 34 patients with preeclampsia were assayed
      for sVEGFR-1, sVEGFR-2, PlGF and sEng by ELISA. Nonparametric paired tests were
      used for analyses. RESULTS: A significant difference between plasma and serum
      concentration was observed for sVEGFR-1 and sVEGFR-2 in normal pregnancy, and for
      sVEGFR-1, sVEGFR-2, PlGF and sEng in women with preeclampsia. CONCLUSION: The
      concentrations of sVEGFR-1, sVEGFR-2, PlGF and sEng when measured in maternal
      plasma and in serum are different. Therefore, the matrix used for the assay
      (serum versus plasma) needs to be considered when selecting thresholds for
      predictive studies and interpreting the growing body of literature on this
      subject.

PMID- 20158397
TI  - Congenital fusion of the thalami (atresia of the third ventricle) associated with
      parietooccipital meningocele.
AB  - In this article we present a case of a male newborn with a CNS malformation that
      is characterized mainly by complete fusion of the thalami resulting in atresia of
      the 3rd ventricle accompanied by fusion of the anterior peduncles of the fornix,
      the presence of a single occult interventricular foramen lying at the midline,
      absence of the septum pellucidum, hypoplasia of the corpus callosum,
      disorganization of the head of the left caudate nucleus, and greatly dilated
      lateral ventricles (hydrocephalus). The patient underwent surgical correction of
      the meningocele on his 4th postnatal day. On his 13th postnatal day he had
      projectile vomiting due to a left parietooccipital hygroma that was drained via a
      shunt. On his 31st postnatal day he developed seizures and marked dilatation of
      the lateral ventricles, for which he underwent a ventriculoperitoneal shunt
      (Brown). On the 14th postoperative day the patient developed aspiration pneumonia
      and died.

PMID- 20158396
TI  - Intra-amniotic infection increases amniotic lamellar body count before 34 weeks
      of gestation.
AB  - OBJECTIVE: To examine the lamellar body count (LBC) value in intra-amniotic
      infection cases and evaluate its association with the incidence of respiratory
      distress syndrome (RDS). METHODS: Three hundred sixty-five amniotic fluid (AF)
      samples were obtained at caesarean section from 27 to 38 weeks of gestation. LBC
      and glucose concentrations in AF were measured with no centrifugation. We defined
      AF glucose concentrations<0.8 mmol/L and positive C-reactive protein (CRP) of the
      neonates as intra-amniotic infection. RESULTS: An LBC cutoff value of 29,500/MUL
      resulted in 94.0% sensitivity, 82.4% specificity, and 99.1% negative predictive
      value (NPV) for RDS. Neonates with glucose concentrations<0.8 mmol/L in AF and
      positive CRP had no RDS and significantly higher LBC values than controls before
      34 weeks of gestation (17.0 vs. 4.3, p<0.05 and 25.5 vs. 5.0, p<0.05,
      respectively), but there were no significant differences after 34 weeks of
      gestation. CONCLUSIONS: LBC is an accurate predictor of foetal lung maturity and
      our LBC cutoff value had a high NPV for predicting RDS. We showed that intra
      amniotic infection was associated with significantly higher LBC values than the
      value in controls before 34 weeks of gestation, which correlated with a low
      incidence of RDS.

PMID- 20158395
TI  - Fetal death: a condition with a dissociation in the concentrations of soluble
      vascular endothelial growth factor receptor-2 between the maternal and fetal
      compartments.
AB  - OBJECTIVE: An anti-angiogenic state has been implicated in the pathophysiology of
      preeclampsia, fetal growth restriction and fetal death. Vascular endothelial
      growth factor (VEGF), an indispensible angiogenic factor for embryonic and
      placental development exerts its angiogenic properties through the VEGF receptor
      (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected
      in maternal blood. The aim of this study was to determine if fetal death was
      associated with changes in the concentrations of sVEGFR-2 in maternal plasma and
      amniotic fluid. STUDY DESIGN: Maternal plasma was obtained from patients with
      fetal death (n = 59) and normal pregnant women (n = 134). Amniotic fluid was
      collected from 36 patients with fetal death and the control group consisting of
      patients who had an amniocentesis and delivered at term (n = 160). Patients with
      fetal death were classified according to the clinical circumstances into the
      following groups: (1) unexplained; (2) preeclampsia and/or placental abruption;
      (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid
      concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics
      and logistic regression analysis were applied. RESULTS: (1) Patients with a fetal
      death had a significantly lower median plasma concentration of sVEGFR-2 than
      normal pregnant women (p < 0.001). The median plasma concentration of sVEGFR-2 in
      patients with unexplained fetal death and in those with preeclampsia/abruption,
      but not that of those with congenital anomalies, was lower than that of normal
      pregnant women (p = 0.006, p < 0.001 and p = 0.2, respectively); (2) the
      association between plasma sVEGFR-2 concentrations and preterm unexplained fetal
      death remained significant after adjusting for potential confounders (OR: 3.2;
      95% CI: 1.4-7.3 per each quartile decrease in plasma sVEGFR-2 concentrations);
      (3) each subgroup of fetal death had a higher median amniotic fluid concentration
      of sVEGFR-2 than the control group (p < 0.001 for each); (4) the association
      between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal
      death remained significant after adjusting for potential confounders (OR: 15.6;
      95% CI: 1.5-164.2 per each quartile increase in amniotic fluid sVEGFR-2
      concentrations); (5) among women with fetal death, there was no relationship
      between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman
      Rho: 0.02; p = 0.9). CONCLUSION: Pregnancies with a fetal death, at the time of
      diagnosis, are characterized by a decrease in the maternal plasma concentration
      of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein.
      Although a decrease in sVEGFR-2 concentration in maternal circulation depends
      upon the clinical circumstances of fetal death, an increase in sVEGFR-2
      concentration in amniotic fluid seems to be a common feature of fetal death. It
      remains to be determined if the perturbation in sVEGFR-2 concentrations in
      maternal and fetal compartments observed herein preceded the death of a fetus.

PMID- 20158399
TI  - Another milestone in minimizing risks to mothers exposed to single-dose
      nevirapine for prevention of vertical transmission of HIV-1 to infants: what
      next?

PMID- 20158400
TI  - Clinical implications of genotypic resistance to the newer antiretroviral drugs
      in HIV-1-infected patients with virological failure.
AB  - Virological suppression rates achieved with the new antiretroviral drugs in
      patients with virological failure and resistance to multiple drug classes are
      nearly matching the rates seen in treatment-naive patients. Knowledge of cross
      resistance patterns to drugs of the same class is key for successful use of
      etravirine, tipranavir, and darunavir in treatment-experienced patients.
      Determination of human immunodeficiency virus type 1 (HIV-1) tropism is cardinal
      for maraviroc. The impressive potency of raltegravir must not preclude its use
      with other active drugs because of its limited genetic barrier. These new agents
      have demonstrated superiority in virtually all efficacy parameters in their
      pivotal salvage trials, but comparative data between them are still very scarce.
      This review discusses the clinical implication of resistance to these new drugs.
      Specific genotypic resistance scores have been developed for tipranavir and
      etravirine, and mutations conferring resistance to darunavir are well understood.
      Determining the most active drugs and successfully combining them is the key
      challenge in salvage regimens.

PMID- 20158398
TI  - Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV
      resistance mutations after intrapartum single-dose nevirapine.
AB  - BACKGROUND: Intrapartum single-dose nevirapine plus third trimester maternal and
      infant zidovudine are essential components of programs to prevent mother-to-child
      transmission of human immunodeficiency virus (HIV) in resource-limited settings.
      The persistence of nevirapine in the plasma for 3 weeks postpartum risks
      selection of resistance mutations to nonnucleoside reverse-transcriptase
      inhibitors (NNRTIs). We hypothesized that a 1-month zidovudine-didanosine course
      initiated at the same time as single-dose nevirapine (sdNVP) would prevent the
      selection of nevirapine-resistance mutations. METHODS: HIV-infected pregnant
      women in the PHPT-4 cohort with CD4 cell counts >250 cells/mm3 received
      antepartum zidovudine from the third trimester until delivery, sdNVP during
      labor, and a 1-month zidovudine-didanosine course after delivery. These women
      were matched on the basis of baseline HIV load, CD4 cell count, and duration of
      antepartum zidovudine to women who received sdNVP in the PHPT-2 trial (control
      subjects). Consensus sequencing and the more sensitive oligonucleotide ligation
      assay were performed on samples obtained on postpartum days 7-10, 37-45, and 120
      (if the HIV load was >500 copies/mL) to detect K103N/Y181C/G190A mutations.
      RESULTS: The 222 PHPT-4 subjects did not differ from matched control subjects in
      baseline characteristics except for age. The combined group median CD4 cell count
      was 421 cells/mm3 (interquartile range [IQR], 322-549 cells/mm3), the median HIV
      load was 3.45 log10 copies/mL (IQR, 2.79-4.00 log10 copies/mL), and the median
      duration of zidovudine prophylaxis was 10.4 weeks (IQR, 9.1-11.4 weeks). Using
      consensus sequencing, major NNRTI resistance mutations were detected after
      delivery in 0% of PHPT-4 subjects and 10.4% of PHPT-2 controls. The
      oligonucleotide ligation assay detected resistance in 1.8% of PHPT-4 subjects and
      18.9% of controls. Major NNRTI resistance mutations were detected by either
      method in 1.8% of PHPT-4 subjects and 20.7% of controls (P < .001). CONCLUSIONS:
      A 1-month postpartum course of zidovudine plus didanosine prevented the selection
      of the vast majority of NNRTI resistance mutations.

PMID- 20158401
TI  - The global burden of nontyphoidal Salmonella gastroenteritis.
AB  - To estimate the global burden of nontyphoidal Salmonella gastroenteritis, we
      synthesized existing data from laboratory-based surveillance and special studies,
      with a hierarchical preference to (1) prospective population-based studies, (2)
      "multiplier studies," (3) disease notifications, (4) returning traveler data, and
      (5) extrapolation. We applied incidence estimates to population projections for
      the 21 Global Burden of Disease regions to calculate regional numbers of cases,
      which were summed to provide a global number of cases. Uncertainty calculations
      were performed using Monte Carlo simulation. We estimated that 93.8 million cases
      (5th to 95th percentile, 61.8-131.6 million) of gastroenteritis due to Salmonella
      species occur globally each year, with 155,000 deaths (5th to 95th percentile,
      39,000-303,000 deaths). Of these, we estimated 80.3 million cases were foodborne.
      Salmonella infection represents a considerable burden in both developing and
      developed countries. Efforts to reduce transmission of salmonellae by food and
      other routes must be implemented on a global scale.

PMID- 20158402
TI  - On understanding the very different science premises meaningful to CAM versus
      orthodox medicine: part I--the fundamentals.
AB  - BACKGROUND: In previous articles by this author and his colleagues in the Journal
      of Alternative and Complementary Medicine, it has been shown that physical
      reality consists of two uniquely different categories of substance, one being
      electric charge-based while the other appears to be magnetic charge-based.
      Normally, only the electric atom/molecule type of substance is accessible by our
      traditional measurement instruments. We label this condition as the uncoupled
      state of physical reality that is our long-studied, electric atom/molecule level
      of nature. The second level of physical reality is invisible to traditional
      measurement instruments when the system is in the uncoupled state but is
      accessible to these same instruments when the system is in the coupled state of
      physical reality. The coupling of these two unique levels has been shown to occur
      via the application of a sufficient intensity of human consciousness in the form
      of specific intentions. Part II of this article (in a forthcoming issue) explores
      the thermodynamics of complementary and 328 alternative medicine (CAM) through
      five different space-time applications involving coupled state physics to show
      their relevance to today's medicine: (1) homeopathy; (2) the placebo effect; (3)
      long-range, room temperature, macroscopic-size-scale, information entanglement;
      (4) explanation for dark matter/energy plus possible human levitation; and (5)
      electrodermal diagnostic devices. The purpose is to clearly differentiate the use
      and limitations of uncoupled state physics in nature and today's traditional
      medicine from coupled state physics in tomorrow's CAM. CONCLUSIONS: Existing
      orthodox science provides the technical underpinnings and mindset for today's
      orthodox medicine. Psycho-energetic science will provide the technical
      underpinnings and mindset for CAM.

PMID- 20158403
TI  - The Office on Women's Health initiative to improve women's heart health: program
      description, site characteristics, and lessons learned.
AB  - AIMS: Improving, Enhancing and Evaluating Outcomes of Comprehensive Heart Health
      Care Programs for High Risk Women has funded six diverse centers to provide
      chronic disease risk factor screening and lifestyle interventions for women and
      focuses specifically on low-income, minority women. RESULTS: This article
      describes the rationale for these diverse programs across the country, all
      focusing on improving outcomes for women with or at risk for cardiovascular
      disease (CVD). The six programs include College of Physicians and Surgeons at
      Columbia University, Christ Community Health Services in Memphis, Women's Heart
      Center of Fox Valley Cardiovascular Consultants, University of Minnesota,
      University of California Davis Women's Cardiovascular Medicine Program, and Yale
      New Haven Hospital's Women's Heart Advantage. CONCLUSIONS: We present six
      differing approaches to women's heart programs. Based on this experience,
      promoting CVD prevention in women is a feasible healthcare delivery strategy for
      health promotion and for delivering preventive strategies for high-risk women. It
      is possible to deliver heart-healthy programs through existing healthcare
      infrastructures. These programs provide important models for public health,
      voluntary, and other health organizations to develop networks for population
      based, targeted, relatively low cost programs that support Healthy People 2010
      objectives for lifestyle changes and cardiovascular health. Ongoing longitudinal
      analysis of the programs will provide information about clinical outcomes and
      sustainability of such programs beyond the funding period.

PMID- 20158404
TI  - Erythropoietic stimulating agents.
AB  - IMPORTANCE OF THE FIELD: The synthesis of recombinant forms of erythropoietin,
      epoetin alpha, beta and darbepoetin alpha, has represented a major achievement in
      anemia therapy. AREAS COVERED IN THIS REVIEW: This review analyzes the
      therapeutic options of existing erythropoietic stimulating agents (ESAs) in
      patients with cancer, renal and heart failure anemia and shows the main features
      of new ESAs under development. Peer-reviewed scientific literature and abstracts
      published during the last 10 years were reviewed. WHAT THE READER WILL GAIN:
      Randomized clinical trials carried out in patients with anemia associated with
      chronic renal disease or malignancies have consistently demonstrated that ESAs
      increase hemoglobin levels, reduce blood transfusion requirements and improve
      quality of life. However, in spite of the positive effects, treatment with ESAs,
      particularly in oncologic patients, is associated with an increased mortality and
      cardiovascular complications. These observations imply the absolute need for
      using ESAs in the context of currently available guidelines. TAKE HOME MESSAGE: A
      razionalization in the clinical use of ESAs according to current guidelines is
      required to improve the benefits derived from therapy with these drugs. New ESAs
      are under development and their introduction in therapy could provide a
      significant improvement in anemia management.

PMID- 20158405
TI  - Does patella resurfacing really matter? Pain and function in 972 patients after
      primary total knee arthroplasty.
AB  - BACKGROUND AND PURPOSE: Resurfacing of the patella during primary total knee
      arthroplasty (TKA) is often recommended based on higher revision rates in non
      resurfaced knees. As many of these revisions are insertions of a patella
      component due to pain, and since only patients with a non-resurfaced patella have
      the option of secondary resurfacing, we do not really know whether these patients
      have more pain and poorer function. The main purpose of the present paper was
      therefore to assess pain and function at least 2 years after surgery for
      unrevised primary non-resurfaced and resurfaced TKA, and secondary among
      prosthesis brands. METHODS: Information needed to calculate subscales from the
      knee injury and osteoarthritis outcome score (KOOS) was collected in a
      questionnaire given to 972 osteoarthritis patients with intact primary TKAs that
      had been reported to the Norwegian Arthroplasty Register. Pain and satisfaction
      on visual analog scales and improvement in EQ-5D index score DeltaEQ-5D) were
      also used as outcomes. Outcomes were measured on a scale from 0 to 100 units
      (worst to best). To estimate differences in mean scores, we used multiple linear
      regression with adjustment for possible confounders. RESULTS: We did not observe
      any differences between resurfacing and non-resurfacing in any outcome, with
      estimated differences of <or= 1.4 units and p-values of > 0.4. There was,
      however, a tendency of better results for the NexGen implant as compared to the
      reference brand AGC for symptoms (difference = 4.9, p = 0.05), pain (VAS)
      (difference = 8.3, p = 0.004), and satisfaction (VAS) (difference = 7.9, p =
      0.02). However, none of these differences reached the stated level of minimal
      perceptible clinical difference. INTERPRETATION: Resurfacing of the patella has
      no clinical effect on pain and function after TKA. Differences between the brands
      investigated were small and they were assumed to be of minor importance.

PMID- 20158407
TI  - Infrainguinal revascularization using the Crosser vibrational system.
AB  - Revascularization of infrainguinal vessels is still a challenge. Complications
      such as flow-limiting dissections or perforation are responsible for a limited
      success rate. Failed revascularization attempt leads to amputation in a
      significant number of patients and increases mortality. We report the use of a
      novel percutaneous device using the CROSSER catheter system in two patients with
      peripheral vascular disease. In case # 1 anterior tibial artery patency was
      restored in a diabetic foot and in case # 2 a chronic traumatic occlusion of the
      superficial femoral artery was revascularized. In both cases the lesion was
      recanalized in a short time without any procedure-related complications. The
      CROSSER catheter system can overcome technical problems and make reentry devices
      and retrograde distal accesses less relevant. It opens new horizons for the
      treatment of complex below-the-knee lesions.

PMID- 20158406
TI  - Gene expression in the brain during reovirus encephalitis.
AB  - Viral encephalitis remains a significant cause of morbidity and mortality
      throughout the world. We performed microarray analysis to identify genes and
      pathways that are differentially regulated during reovirus encephalitis and that
      may provide novel therapeutic targets for virus-induced diseases of the central
      nervous system (CNS). An increase in the expression of 130 cellular genes was
      found in the brains of reovirus-infected mice at early times post infection,
      compared to mock-infected controls. The up-regulation of these genes was
      consistent with activation of innate immune responses, particularly interferon
      signaling. At later times post infection, when significant CNS injury is present
      and mice exhibit signs of severe neurologic disease, many more (1374) genes were
      up-regulated, indicating that increased gene expression correlates with disease
      pathology. Virus-induced gene expression at late times post infection was again
      consistent with the activation of innate immune responses. However, additional
      significant pathways included those associated with cytokine signaling and
      apoptosis, both of which can contribute to CNS injury. This is the first report
      comparing virus-induced cellular gene and pathway regulation at early and late
      times following virus infection of the brain. The shift of virus-induced gene
      expression from innate immune responses at early times post infection to cytokine
      signaling and apoptosis at later times suggests a potential therapeutic strategy
      that preserves early protective responses whilst inhibiting later responses that
      contribute to pathogenesis.

PMID- 20158408
TI  - The contribution of hysteroscopy to the detection malignancy in symptomatic
      postmenopausal women.
AB  - Hysteroscopic evaluation of endometrial cavity is widely used in cases of
      abnormal uterine bleeding. The aim of the present study is to compare the
      hysteroscopic and histological findings in women suffering from postmenopausal
      bleeding. Between 1990 and 2009, 425 women aged 47-83 years were included in the
      study. None of the women had received hormonal therapy or had any malignancy in
      the past. All women underwent diagnostic hysteroscopy and histologic sampling of
      the endometrial cavity. Hysteroscopy was successfully completed in 423 women and
      was suggestive of malignant lesions in 23 cases, which were confirmed
      histologically. The hysteroscopic findings in three cases were suggestive of
      atrophic endometrium, atypical hyperplasia and endometrial carcinoma, and the
      histologic diagnosis confirmed endometrial carcinoma (two cases) and one uterine
      sarcoma. Hysteroscopy proves to be a safe and effective technique in the
      diagnosis and management of abnormal uterine bleeding.

PMID- 20158409
TI  - Experimental model as training tool in endoscopic axillary dissection.
AB  - Endoscopic axillary lymphatic dissection is a viable surgical option, but has not
      been taken with great enthusiasm; several factors have accounted for this,
      including the lack of an effective experimental model to acquire skills and
      abilities. The aim of this study was to develop a training tool for endoscopic
      axillary dissection and to evaluate its applicability in a porcine model. Twenty
      endoscopic dissections of the axilla were performed in ten female pigs of four to
      six months by a single surgeon with blunt dissection and CO(2). A surgical
      workflow was divided into temporal operative phases. Time necessary to perform
      this action was compared throughout the study. The mean dissection time was 26 +/
      7 minutes. The axillary content was separated from the other anatomical elements
      under complete visualization (85%). Intraoperative complications occurred in two
      dissections (10%). Residual fibrofatty tissue was removed from the axilla in
      three dissections. This data defined a pig model for commencement of training in
      endoscopic axillary dissection in the laboratory. Bringing these core elements
      together led to the development of a model for acquiring advanced laparoscopic
      skills, which may be applicable to other endoscopic axillary procedures.

PMID- 20158410
TI  - The operation room as a hostile environment for surgeons: physical complaints
      during and after laparoscopy.
AB  - Due to suboptimal ergonomic conditions during laparoscopic procedures, surgeons
      are exposed to physical strain on the upper extremity. The primary objective of
      this study was to assess the prevalence of physical complaints among laparoscopic
      surgeons and to assess the factors that influence these complaints. A
      questionnaire was distributed in a university hospital to all surgeons who
      perform laparoscopic procedures. Participants were asked to answer questions
      related to experience, physical complaints during or after laparoscopic
      procedures and the possible causes of their complaints. Fifty-five out of 92
      (60%) surgeons completed the questionnaire. In this group, 40 surgeons (73%)
      reported physical complaints during or after laparoscopic procedures, mainly
      involving neck, lower back, shoulders and thumbs. Significantly more surgeons
      reported complaints in the dominant upper extremity compared to the non-dominant
      side. Poor table height adjustment, bad monitor positioning and suboptimal design
      of instrument handles were reported as important causes of complaints. Physical
      complaints of the dominant upper extremity are common among laparoscopic
      surgeons, especially less experienced surgeons. The dominant upper extremity
      appears to be more involved than the non-dominant side. More awareness and
      implementation of ergonomic guidelines is needed.

PMID- 20158411
TI  - Newly developed haptic forceps enables sensitive, real-time measurements of organ
      elasticity.
AB  - Currently available master-slave manipulators cannot recognize the elasticity of
      organs or tissues. The aim of this study was to examine whether a newly developed
      haptic forceps using a linear motor could measure the elasticity of living organs
      using an animal model. We measured the elasticity values and the disruption limit
      values of rat organs using the new haptic forceps. The elasticity of the
      materials was calculated using the formula "power / position", with N/m as the
      unit. We successfully and reproducibly measured the changes in the elasticity
      values of various materials in real time. We were also able to perceive tactile
      changes transmitted through the forceps. The changes in gastrointestinal
      contraction were synchronized with the visually observed changes, and these
      changes were monitored and measured as elasticity values in real time using the
      forceps. The damage limits were also successfully measured. In conclusion, the
      new haptic forceps enabled highly sensitive, real-time measurements of elasticity
      in living rat organs. The use of this forceps enables the disruption limit values
      of organs to be measured, and the device could be useful for setting safety
      limits when grasping organs during endoscopic surgery.

PMID- 20158412
TI  - Salvage of a subacute failure in femoral dialysis loop graft using stent covering
      the arterial and venous anastomosis.
AB  - Endovascular treatment can be considered the first line therapy in the majority
      of dysfunctioning arteriovenous fistula. However, when early thrombosis of the
      arteriovenous access occurs, surgical treatment is recommended. In these cases,
      technical problems are the most frequent cause of the malfunction. We report a
      case of a subacute thrombosis of an arteriovenous fistula, femoral artery to
      femoral vein looped ePTFE with venous anastomosis occlusion and subocclusion
      lesion at the arterial anastomosis. Both anastomoses were treated using self
      expandable stents, and no other intervention was necessary until the one-year
      follow-up for maintain patency.

PMID- 20158413
TI  - Neural fibrolipoma of a digital nerve of the index finger without macrodactyly.
AB  - We present a case of neural fibrolipoma arising from the digital nerve in the
      index finger of the right hand. A 31-year-old man was referred with a soft tissue
      mass in the ulnar aspect of the index finger of his right hand, which had
      gradually enlarged during the past seven years. Histological examination of an
      excisional biopsy specimen identified a neural fibrolipoma, which is a
      differential diagnosis of a lipomatous lesion of the digits.

PMID- 20158414
TI  - Microsurgical replantation of an ear with no venous repair.
AB  - Replantation of an avulsed ear was completely successful with only arterial
      repair (to the superficial temporal artery) and the use of medicinal leeches.

PMID- 20158415
TI  - Pharyngoplasty after primary repair of clefts of the secondary palate.
AB  - Our aim was to identify factors associated with the incidence of pharyngoplasty
      in patients with clefts of the secondary palate (CP). We studied 351 children
      born between 1968 and 1999 with CP alone, who had their primary operation at the
      Department of Plastic Surgery, Rikshospitalet University Hospital, Oslo, Norway.
      Data were collected retrospectively from the archives of the Oslo Cleft Team.
      During the study period 1968-2007, 68 children (19%) had a pharyngoplasty to
      improve their speech. Mean follow up time from the primary operation was 16 years
      (range 2-37). The estimated incidence of pharyngoplasty at 5, 7, 10, and 15 years
      after the primary operation was 9%, 12%, 14%, and 15%, respectively. Thirty-one
      (46%) of the pharyngoplasties were done more than seven years after the primary
      palatal repair. Children with total clefts of the secondary palate had a
      pharyngoplasty more often than children with clefts of the soft palate alone (7
      years incidence: 11 (42%) compared with 22 (10%), p<0.001). Sex, age at time of
      primary operation, and surgeon's experience were not significantly associated
      with the necessity for pharyngoplasty. Our study suggested that the necessity for
      pharyngoplasty is related to the severity of clefts, and duration of observation.

PMID- 20158416
TI  - Ileal patch graft used to repair a bladder injured during repair of an abdominal
      wall hernia.
AB  - A 72-year-old woman had her bladder injured accidentally during repair of a
      severe hernia of the abdominal wall. Primary closure was impossible because of
      previous heavy irradiation. We therefore did an ileocystoplasty to cover the
      defect. Her postoperative course was uneventful, and she could void spontaneously
      at seven months postoperatively.

PMID- 20158417
TI  - Formation of osteocartilaginous exostosis resulting from the raising of a lateral
      supramalleolar flap.
AB  - An osteocartilaginous exostosis developed in a 4-year-old boy in whom a distally
      based lateral supramalleolar adipofascial flap had been used to cover a defect in
      the dorsum of the foot. The bony exostosis was first noticed four months after
      the operation. It was excised with no complications and there has been no
      recurrence after two years follow-up. The exostosis was thought to result from
      stripping the perichondrium over the epiphyseal plate while the flap was being
      raised. This unique complication has not to our knowledge been reported after
      harvest of a flap before.

PMID- 20158418
TI  - Secondary reconstruction of vaginal stenosis with bilateral pudendal thigh flaps.
AB  - We report the cases of two patients who had pronounced stenosis of the lower part
      of the vagina after vaginal reconstruction for congenital vaginal aplasia and
      hypoplasia. Bilateral pudendal thigh flaps were used for secondary
      reconstruction, and gave satisfactory results with no signs of recurrence or
      severe scarring at the donor site.

PMID- 20158419
TI  - Supracondylar process of the humerus: a rare case with compression of the ulnar
      nerve.
AB  - A patient presented with a 6-month history of numbness and pain in the left
      forearm and hand over the ulnar nerve distribution. Radiographs showed a
      supracondylar process, which was excised. The ulnar nerve had been compressed.
      The patient was symptom-free two months postoperatively.

PMID- 20158420
TI  - Interosseous epidermoid cyst at the base of the distal phalanx.
AB  - Interosseous epidermoid cysts of the phalanges are rare, particularly at the base
      of the phalanx and if the lesion is tender. We report a case of a tender
      interosseous epidermoid cyst at the base of the distal phalanx of a young man.

PMID- 20158421
TI  - Injection injury caused by puncture of the nozzle of a spray can.
AB  - We present a case of low-pressure injection injury of the left index finger
      caused by puncture of the nozzle of a spray can. It resulted in symptoms as
      severe as those from a high-pressure injection injury. Several debridements meant
      that the finger did not have to be amputated. The raw surface was covered with a
      V-Y advancement flap.

PMID- 20158422
TI  - Simplified dorsal approach to fracture of the hamate hook with percutaneous
      fixation with screws.
AB  - We present a new method for treating a fracture of the hook of the hamate with a
      percutaneous screw using a dorsal approach. Through this small incision, the
      fracture may be fixed easily and safely while avoiding damage to the blood supply
      of the hamate and the surrounding soft tissue.

PMID- 20158423
TI  - Fat embolism syndrome after combined aesthetic surgery.
AB  - Fat embolism syndrome is a rare complication that develops after extended soft
      tissue disruption by liposuction, in particular if combined with time consuming,
      multiple procedures. Early signs are non-specific and often not considered, so
      that diagnosis and correct management may be delayed. We report a case in which
      liposuction combined with other aesthetic surgical procedures caused a fat
      embolism syndrome in a 46-year-old woman, which was followed by multiple organ
      failure and the development of sepsis with perimammary abscesses. Extended
      liposuction of the abdomen and thighs, bilateral augmentation mammaplasty, and
      stripping of both greater saphenous veins were combined.

PMID- 20158424
TI  - Malunion of fractures of the proximal phalangeal neck in children.
AB  - We report three cases of malunion after fractures of the proximal phalangeal neck
      in children. A 12-year-old boy and a 7-year-old girl had malunited fractures with
      dorsal and ulnar deviation of their fingers. Several years later remodeling had
      been achieved well for dorsal deviation but little for the ulnar deviation in
      each case. A 10-year-old boy had a similar malunited fracture with dorsal and
      ulnar deviation of his finger. The proximal bony spike, which protruded to the
      volar side, collided with the middle phalanx during flexion of the proximal
      interphalangeal (PIP) joint, so we shaved it. One year after operation, flexion
      of the PIP joint had improved. In cases of these malunited fractures in children,
      remodeling is considered possible for dorsal deviation but difficult for ulnar
      deviation. Surgical shaving of the protruding bone should be considered.

PMID- 20158425
TI  - Successful management of tracheoinnominate artery fistula using a split
      pectoralis muscle flap with anatomical reconstruction by a synthetic graft.
AB  - We report the successful repair for tracheoinnominate fistula, in which the
      innominate artery was interposed with a synthetic graft and the pectoralis muscle
      was used as a seal against infection. We know of 10 other reported cases.

PMID- 20158426
TI  - Incidence, epidemiology, and operative outcome of replantation or
      revascularisation of injury to the upper extremity.
AB  - We retrospectively studied the epidemiology of adult patients admitted for
      possible replantation or revascularisation of an injured upper extremity during
      the period June 2003 to May 2008. A total of 121 patients were admitted (71
      graded severe), mean 24 (14 graded severe), being admitted each year. The annual
      rate of amputation injuries in the referral area of 1.5 million was 1.5/100 000
      and for severe amputation injuries 0.9/100 000. Most injuries occurred in
      patients aged 41-50. Fifty-eight patients had the accident during working hours
      (36 severe), and 62 during leisure time (34 severe). The survival rate for
      subtotal amputations was 77% and for total amputations 55%. Of 15 further
      vascularisation procedures, two succeeded at the metacarpal level. Most of the
      accidents occurred during wood-processing with circular saws or powered wood
      splitters. More efforts should focus on preventing such injuries.

PMID- 20158427
TI  - Munchausen syndrome: A differential diagnostic trap for hand surgeons.
AB  - A 24-year-old woman was referred with an extremely painful, stiff, swollen, and
      hypersensitive right upper extremity. She had history of four previous operations
      on the same extremity. The primary diagnosis was complex regional pain syndrome.
      During the next few days her symptoms worsened and she developed fever. It was
      discovered that the patient was preheating more than one thermometer and was
      intentionally injuring herself. The final diagnosis was Munchausen syndrome.

PMID- 20158428
TI  - SmartHand tactile display: a new concept for providing sensory feedback in hand
      prostheses.
AB  - A major drawback with myoelectric prostheses is that they do not provide the user
      with sensory feedback. Using a new principle for sensory feedback, we did a
      series of experiments involving 11 healthy subjects. The skin on the volar aspect
      of the forearm was used as the target area for sensory input. Experiments
      included discrimination of site of stimuli and pressure levels at a single
      stimulation point. A tactile display based on digital servomotors with one
      actuating element for each of the five fingers was used as a stimulator on the
      forearm. The results show that the participants were able to discriminate between
      three fingers with an accuracy of 97%, between five fingers with an accuracy of
      82%, and between five levels with an accuracy of 79%. The tactile display may
      prove a helpful tool in providing amputees with sensory feedback from a
      prosthetic hand by transferring tactile stimuli from the prosthetic hand to the
      skin at forearm level.

PMID- 20158429
TI  - Malignant melanoma in association with or mimicking blue naevus.
AB  - Malignant blue naevus is a rare but highly aggressive form of cutaneous malignant
      melanoma, which spreads often and early to the regional lymph nodes, liver,
      lungs, and other organs. We report three cases, review published reports, and
      recommend treatment.

PMID- 20158430
TI  - A rare anatomical variant of the thenar branch discovered during open
      decompression of the median nerve.
AB  - We describe a rare anatomical variant of the thenar branch of the median nerve
      during open release of the carpal tunnel. The thenar branch originated from the
      ulnar side of the median nerve and traversed supraligamentously close to the top
      of the transverse ligament. A high resolution clinical photograph shows the
      relation between the anatomical structures when the thenar variant is present in
      the carpal tunnel. This is one of the dangers faced by surgeons when doing open
      or endoscopic release of the carpal tunnel.

PMID- 20158431
TI  - New method of tunnelling for omental transposition in the treatment of a complex
      radionecrotic groin ulcer.
AB  - Omental transposition is often used for reconstruction of soft tissue in the
      groin. However, the potential for incisional hernia is a relative
      contraindication. We report the cure of a groin ulcer with omental transposition
      using a new method of tunnelling to avoid herniation.

PMID- 20158432
TI  - Anomalies of the arterial tree that coexist with arteriovenous malformations in
      the lower extremity.
AB  - Several previous reports have documented arteriovenous malformations associated
      with anomalies of the arterial tree. We report two cases in which a malformation
      on the foot coexisted with arterial variants of the popliteal artery. Careful
      therapeutic planning was required to avoid jeopardising perfusion to the distal
      area.

PMID- 20158433
TI  - Superior-capsular elongation and its significance in atraumatic posteroinferior
      multidirectional shoulder instability in magnetic resonance arthrography.
AB  - BACKGROUND: Redundancy of the capsule has been considered to be the main
      pathologic condition responsible for atraumatic posteroinferior multidirectional
      shoulder instability; however, there is a paucity of measurements providing
      quantitative diagnosis. PURPOSE: To determine the significance of superior
      capsular elongation and its relevance to atraumatic posteroinferior
      multidirectional shoulder instability at magnetic resonance (MR) arthrography.
      MATERIAL AND METHODS: MR arthrography was performed in 21 patients with
      atraumatic posteroinferior multidirectional shoulder instability and 21 patients
      without shoulder instability. One observer made the measurements in duplicate and
      was blinded to the two groups. The superior-capsular measurements (linear
      distance and cross-sectional area) under the supraspinatus tendon, and the
      rotator interval were determined on MR arthrography and evaluated for each of the
      two groups. RESULTS: For the superior-capsular measurements, the linear distance
      under the supraspinatus tendon was significantly longer in patients with
      atraumatic posteroinferior multidirectional shoulder instability than in control
      subjects (P<0.001). The cross-sectional area under the supraspinatus tendon, and
      the rotator interval were significantly increased in patients with atraumatic
      posteroinferior multidirectional shoulder instability compared to control
      subjects (P<0.001 and P=0.01, respectively). Linear distance greater than 1.6 mm
      under the supraspinatus tendon had a specificity of 95% and a sensitivity of 90%
      for diagnosing atraumatic posteroinferior multidirectional shoulder instability.
      Cross-sectional area under the supraspinatus tendon greater than 0.3 cm(2), or an
      area under the rotator interval greater than 1.4 cm(2) had a specificity of more
      than 80% and a sensitivity of 90%. CONCLUSION: The superior-capsular elongation
      as well as its diagnostic criteria of measurements by MR arthrography revealed in
      the present study could serve as references for diagnosing atraumatic
      posteroinferior shoulder instability and offer insight into the spectrum of
      imaging findings corresponding to the pathologies encountered at clinical
      presentation.

PMID- 20158434
TI  - Time to 'get real': preliminary insights into the long-term management of
      schizophrenia.
AB  - OBJECTIVE: A brief file and medication chart review was undertaken to examine the
      'real world' treatment of schizophrenia, with a particular focus on long-term
      treatment strategies that extend beyond existing evidence-based guidelines.
      METHOD: Treatment strategies were identified through an audit of patient files
      and their medication charts for patients admitted 2-5 years in a non-acute
      psychiatric hospital. RESULTS: Twenty-nine file reviews and 20 medication chart
      audits were conducted. High levels of diagnostic heterogeneity were identified
      with the presence of psychosis and mood-related diagnoses (primarily
      schizophrenia and schizoaffective disorder) and high rates of comorbidity (86%).
      Functional impairment, poor insight and high levels of risk were present in most
      patients. Treatments largely consisted of combination strategies with 75% of
      patients prescribed two or more antipsychotics and an average of 3.4 psychotropic
      medications in total. While clozapine was commonly prescribed (65%), this was
      often in combination with, on average, two other psychotropic agents.
      CONCLUSIONS: Notwithstanding the limited sample, these findings provide a
      valuable glimpse into the management strategies employed in the long-term
      management of schizophrenia. Evidence-based guidelines are largely of limited
      value for this cohort that often has complex presentations and further research
      is urgently needed to provide guidance into management strategies that extend
      beyond 5 years, with particular emphasis on the utility of medication
      combinations.

PMID- 20158435
TI  - To medicate or not to medicate, when diagnosis is in question: decision-making in
      first episode psychosis.
AB  - OBJECTIVE: This paper reports on a brief survey of clinicians' judgements when
      making treatment decisions in the context of diagnostic uncertainty.
      Specifically, attitudes and opinions were sought from practising consultant
      psychiatrists regarding two key areas of clinical decision-making in first
      episode psychosis (FEP), namely, when to initiate medication and, how long to
      continue treatment. METHOD: Interviews were conducted with consultant
      psychiatrists using a combination of structured and semi-structured questions
      that examined and explored pharmacological treatment decisions in FEP. RESULTS:
      Twenty-three consultant psychiatrists participated in the interviews. The
      threshold to initiate pharmacological treatment was lower when a risk to self or
      others is present, when symptoms are primarily positive, when the patient is in
      distress, or where there is a family history of mental illness. Atypical
      antipsychotics are routinely used as front-line medication in FEP and the choice
      of medication is determined largely by their likely side effect profile. However,
      the greater the perceived efficacy, the greater the anticipated tolerability
      burden. The ideal duration of treatment is considered to be 1-2 years in
      instances of full remission, and 5 years where only a partial response has been
      achieved or where recovery has not been sustained. CONCLUSIONS: The 'first
      episode' represents a unique period in the management of psychosis where by
      definition there is no history of pattern of illness, diagnostic certainty is
      rare, and the patient usually does not have any prior exposure to medications.
      Therefore, each management decision needs to be considered following a risk
      benefit analysis which takes into account the context of the individual.

PMID- 20158436
TI  - Brain-targeted delivery of Tempol-loaded nanoparticles for neurological
      disorders.
AB  - Brain-targeted Tempol-loaded poly-(lactide-co-glycolide) (PLGA) nanoparticles
      (NPs) conjugated with a transferrin antibody (OX 26) were developed using the
      nanoprecipitation method. These NPs may have utility in treating
      neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease.
      Central to these diseases is an increased production of reactive oxygen and
      nitrogen species which may take part in the development of these conditions. As
      proof of principle, the NPs were loaded with Tempol, a free radical scavenger
      that has been shown to be protective against oxidative insults. To enhance the
      delivery of NPs to the central nervous system (CNS), we conjugated the
      transferrin receptor antibody covalently to PLGA NPs using the NHS-PEG3500
      Maleimide crosslinker. The NPs showed a particle size suitable for blood brain
      barrier (BBB) permeation (particle size 80-110 nm) and demonstrated a sustained
      drug release behavior. A high cellular uptake of antibody-conjugated NPs was
      demonstrated in RG2 rat glioma cells. The ability of the Tempol-loaded NPs to
      prevent cell death by resveratrol in RG2 cells was determined using the MTT
      assay. The conjugated NPs containing Tempol were more effective in preventing
      cell viability by resveratrol when compared with unconjugated NPs or free Tempol
      in solution. Our findings suggest that transferrin-conjugated NPs containing
      antioxidants may be useful in the treatment of neurodegenerative diseases.

PMID- 20158437
TI  - Validation of a Rb+ uptake assay for the mouse embryonic stem cell-derived
      cardiomyocytes Na+, K+ ATPase.
AB  - Human Na+, K+ ATPase, an ATP-driven ion transporter, is an emerging drug target
      for heart-related conditions. Three types of assays including purified enzyme,
      radiotracer flux, and cold Rb+ flux have been used to determine the activity of
      this transporter. As an alternative to primary cardiomyocytes, mouse embryonic
      stem cells-derived cardiomyocytes with functional expression of essential cardiac
      ion channels were used in the present studies. The results on its pharmacology
      with digitoxin and ouabain, the 2 well-known cardioglycosides, imply that these
      cardiomyocytes can be used as a predictive model for the identification of
      modulators of Na+, K+ ATPase in HTS format.

PMID- 20158438
TI  - The Seventh Annual Ion Channel Retreat Vancouver, Canada, June 29-July 1, 2009.
AB  - Seven years ago, Aurora Biomed Inc. (Vancouver, BC) recognized the need to create
      a forum for scientific discourse spanning the spectrum of ion channel
      disciplines. Since then, researchers from both academia and industry have been
      invited each year to share their knowledge on the advancement of ion channel
      research and technology, drug discovery, and safety pharmacology. Aurora Biomed's
      2009 Retreat continued this tradition by covering a variety of topics including
      Ion Channels as Disease and Pain Targets, TRP Ion Channels, Ion Channel Screening
      Technologies, Ion Channels in Safety Pharmacology, Structure & Function of Ion
      Channels, Ion Channels in Disease Pathology, and New Horizons in Life Sciences.

PMID- 20158439
TI  - Single cell network profiling (SCNP): mapping drug and target interactions.
AB  - Measuring target coverage of small molecule inhibitors is paramount-first, for
      selection of molecules to progress through the drug development process and
      second, once a candidate drug moves to clinical testing, for guiding
      dose/schedule selection. Single cell network profiling (SCNP) using
      multiparameter flow cytometry can measure compound effects on multiple signaling
      cascades in a cell-type-specific manner. We applied SCNP to a panel of compounds
      with reported inhibitory effects on Jak/Stat signaling using a novel system where
      modulation of multiple signaling cascades are simultaneously measured in discrete
      cell subsets in whole (ie, unfractionated) blood. Jak2 vs. Jak3 selectivity as
      well as "off-target" effects on other cell signaling pathways were measured using
      a combination of cytokines that target different white blood cell subsets, namely
      GM-CSF (monocytes/granulocytes), IL-2 (T cells), and CD40L (B cells). The
      compounds were then rank-ordered by potency and selectivity against the different
      pathways tested. Notably, SCNP performed in whole unfractionated blood compared
      to fractionated peripheral blood mononuclear cells (PBMC) from the same donors
      revealed potency loss for all compounds, with one exception. These studies show
      that SCNP can be used to efficiently measure a drug candidate's potency and
      selectivity in a physiologically relevant environment (eg, whole blood) and that
      robust IC(50) are attainable from rare subpopulations (<100 cells). The ability
      to generate in vitro IC(50) measurements in whole blood can be used not only for
      the preclinical selection of lead molecules, but also to determine the target
      plasma concentration for clinical studies and to measure target coverage after
      drug administration in early phase clinical trials. Knowledge of the compound
      plasma concentration necessary to achieve biochemical coverage permits rational
      design of clinical trials based on biologically active dose vs. the traditional
      maximum tolerated dose (MTD) design, which is better suited for cytotoxic,
      nontargeted drugs.

PMID- 20158440
TI  - Effects of different dose of FK506 on endocrine function of pancreatic islets and
      damage of beta cells of pancreatic islets in a Wistar rat model.
AB  - BACKGROUND AND AIM: To probe into the effects of different doses of FK506 on
      endocrine function of pancreatic islets in Wistar rats. METHODS: Wistar rats were
      randomly divide into control group A (0mg/kg/d) and experimental group B
      (1mg/kg/d), C (3mg/kg/d), D (10mg/kg/d) treated with FK506. In an intraperitoneal
      glucose tolerance test, plasma glucose, insulin and C-peptide were measured with
      a glucose analyzer and ELISA. The ultra-structure of beta cells of pancreatic
      islets were assayed with an electric microscope. RESULTS: In the intraperitoneal
      glucose tolerance test, the level of plasma glucose increased with an increasing
      of dose of FK506 and the level of plasma insulin and C-peptide decreased with an
      increasing of dose of FK506. The result of the plasma glucose level showed no
      significant difference among groups A, B, C, and D at 0 and 120 min P>or=0.05,
      and result of plasma glucose level show significant differences among groups A,
      B, C, D at 30, 60 and 90 min, P<0.05. The result of the plasma insulin level
      showed significant difference among groups A, B, C, and D at 0, 30, 60, 90 min
      P<0.05.The result of the plasma C-peptide level showed no significant difference
      among groups A, B, C, and D at 0 min P> 0.05, and the result of plasma C-peptide
      level showed significant differences in groups A, B, C, and D at 30, 60, 90 and
      120 min, P<0.05.With electric microscope assay, the endocrine secretory granules
      decreased in experiment group. There is some vacuolization in the beta cells of
      pancreatic islets in group D. CONCLUSION: It was shown in the study that
      disorders of glucose metabolism induced by FK506 were related to the dosage of
      FK506.

PMID- 20158441
TI  - Development and validation of a transcreener assay for detection of AMP- and GMP
      producing enzymes.
AB  - Screening of AMP- and GMP-producing enzymes such as phosphodiesterases (PDEs),
      ligases, and synthetases would be simplified by the ability to directly detect
      unmodified nucleoside monophosphates. To address this need, we developed
      polyclonal and monoclonal antibodies that recognize AMP and GMP with nanomolar
      sensitivity and high selectivity vs. the corresponding triphosphate and 3',5'
      cyclic monophosphate nucleotides that serve as substrates for many enzymes in
      these classes. One of these antibodies was used to develop a Transcreener AMP/GMP
      assay with a far red fluorescence polarization (FP) readout. This polyclonal
      antibody exhibited extremely high selectivity, with IC(50) ratios of 6,000 for
      ATP/AMP, 3,810 for cAMP/AMP, and 6,970 for cGMP/GMP. Standard curves mimicking
      enzymatic conversion of cAMP, cGMP, and ATP to the corresponding monophosphates
      yielded Z' values of >0.85 at 10% conversion. The assay reagents were shown to be
      stable for 24 h at room temperature, both before and after dispensing. The
      Transcreener AMP/GMP FP assay was used for enzymatic detection of cGMP- and cAMP
      dependent PDEs 4A1A, 3A, and 9A2 and ATP-dependent ligases, acetyl CoA
      synthetase, and ubiquitin- activating enzyme (UBE1). Shifts of >100 mP were
      observed in the linear part of the progress curves for all enzymes tested, and
      the PDE isoforms exhibited the expected substrate and inhibitor selectivity.
      These studies demonstrate that direct immunodetection of AMP and GMP is a
      flexible, robust enzyme assay method for diverse AMP- and GMP-producing enzymes.
      Moreover, it eliminates many of the shortcomings of other methods including the
      need for fluorescently labeled substrates, the low signal:background inherent in
      substrate depletion assays, and the potential for interference with coupling
      enzymes.

PMID- 20158442
TI  - Risk factors in human immunodeficiency virus/acquired immunodeficiency syndrome
      patients undergoing antiretroviral therapy in the state of Pernambuco, Brazil: a
      case-control study.
AB  - BACKGROUND: Although human immunodeficiency virus (HIV)-associated lipodystrophy
      has been reported for more than a decade, there is still considerable uncertainty
      regarding the mechanisms involved in its pathogenesis. METHODS: A case-control
      study was performed that aimed to identify the risk factors for lipodystrophy in
      HIV/acquired immunodeficiency syndrome (AIDS) patients undergoing antiretroviral
      therapy in Pernambuco, Brazil. RESULTS: Between July and November, 2007, a total
      of 332 patients were enrolled in the study: 182 cases and 150 controls. The
      following factors were independently associated with lipodystrophy: Use of
      stavudine [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.3-6.9], use of
      didanosine (OR, 1.8; 95% CI, 1.0-3.4), use of lopinavir/ritonavir for less than 3
      years (OR, 0.5; 95% CI, 0.2-1.0) and use of nucleoside/nucleotide analogue
      reverse transcriptase inhibitors (NTRIs) for more than 3 years (OR, 2.9; 95% CI,
      1.6-5.2). Other associated factors were: duration of antiretroviral therapy (OR,
      4.3; 95% CI, 2.4-7.9) and duration of HIV infection (OR, 2.9; 95% CI, 1.8-4.7).
      There was no association with the use of protease inhibitor when it was adjusted
      for the use of NRTIs. CONCLUSION: In this study, factors related to
      antiretroviral therapy were the main risk factors for lipodystrophy,
      corroborating the literature, but the findings also point to the need for further
      exploration into some of these associations, especially with the use of
      didanosine and lopinavir/ritonavir, which are less frequently reported. Future
      studies with a larger number of patients and a prospective design could provide
      valuable information for understanding this disorder.

PMID- 20158443
TI  - Cardiovascular risk factors and gamma-glutamyltransferase fractions in healthy
      individuals.
AB  - BACKGROUND: Serum gamma-glutamyltransferase activity (GGT), even when within its
      normal reference range, catalyzes low density lipoprotein oxidation in vitro and
      predicts cardiovascular events. Of the four GGT fractions (b-GGT, m-GGT, s-GGT,
      and f-GGT) recently identified in blood, only b-GGT is found within
      atherosclerotic plaques. Our goal was to identify the determinants of the GGT
      fractions (b-, m-, s-, and f-GGT) and their association with established
      cardiovascular risk factors in healthy subjects. METHODS: Multiple linear
      regression analysis was applied to estimate the association of fractional GGT
      with gender, age, body mass index, arterial pressure (AP), plasma glucose,
      alanine aminotransferase (ALT), high and low density lipoproteins (LDL-C)
      cholesterol (HDL-C), triglycerides (TG) and C-reactive protein (CRP) in 200
      healthy subjects. RESULTS: All GGT fractions were associated with ALT; b-GGT with
      AP, TG, and CRP; m-GGT with LDL-C, TG and CRP; s-GGT with TG and CRP, and f-GGT
      only with LDL-C, whereas gender was associated with s-GGT and f-GGT only.
      CONCLUSIONS: In healthy individuals, cardiovascular risk factors are associated
      with high molecular weight GGT fractions, namely with b-GGT, the only form
      present within the plaque. This finding adds to the present knowledge concerning
      the relevance of GGT, within its reference range, for atherosclerosis-related
      events.

PMID- 20158444
TI  - Extracellular haemoglobin, oxidative stress and quality of red blood cells
      relative to perioperative blood salvage.
AB  - BACKGROUND: The quality of blood-pack units in perioperative blood salvage was
      studied with respect to the presence of extracellular haemoglobin (Hb) and in
      terms of oxidative stress and the mechanical properties of red blood cells (RBC).
      METHODS: The study was performed on blood-pack units and patients' blood after
      retransfusion. Results were compared to those obtained in patients prior to
      autotransfusion. Free Hb, non-protein thiols (as antioxidant marker) and markers
      of oxidative stress (conjugated dienes, thiobarbituric reactive substances and
      protein carbonyl content) were measured. The mechanical properties of RBC were
      evaluated by their osmotic fragility, membrane fluidity by measuring the
      fluorescence anisotropy of an extrinsic probe and permeability by measurement of
      extracellular K(+) and lactate dehydrogenase. RESULTS: Despite washing,
      extracellular Hb concentrations remained high (up to 0.7 g/L in blood-pack units)
      and was associated with a decrease of haptoglobin in patients, despite a
      concomitant inflammatory syndrome. In blood-pack units, we observed a decrease in
      antioxidant markers along with an increase in oxidative stress markers in
      association with an alteration of RBC membrane properties. CONCLUSIONS:
      Haemolysis must be limited during perioperative blood salvage in order to prevent
      exposure to oxidative stress and improve the efficiency of autotransfusion.

PMID- 20158445
TI  - A new statistical method for evaluating long-term analytical performance of
      laboratories applied to an external quality assessment scheme for flow cytometry.
AB  - BACKGROUND: The Belgian External Quality Assessment Scheme for Flow Cytometry
      evaluates the long-term analytical performance of participating laboratories by
      calculating a regression line between the target and reported values of each
      parameter for each laboratory during the past 3 years. This study aims to develop
      a method to find laboratories with aberrant variability or bias using robust
      techniques and to obtain robust estimates of the variability. METHODS: A method
      is proposed to find outliers with respect to the individual regression line,
      followed by a step to find regression lines with excessive variability and
      finally a step to find regression lines with high bias. RESULTS: The model was
      applied to the results obtained by 52 laboratories for CD4%. From the 1340 data
      points, 35 were determined to be regression outliers. The second step revealed
      one regression line with excessive variability; the third step detected three
      regression lines with exceeding bias. CONCLUSIONS: The methodology allows
      assessment of the long-term performance of laboratories, taking into account
      samples with different target values. Outliers in the first step indicate
      accidental mistakes, outliers in the second and third step point to high
      analytical variability or bias.

PMID- 20158447
TI  - Mediterranean diet and the metabolic syndrome: the end of the beginning.
AB  - The metabolic syndrome is now both a public health and a clinical problem. The
      most recent estimates from the National Health and Nutrition Examination Survey
      (NHANES) 2003-2006 reported that approximately 34% of adults in the United States
      have the metabolic syndrome. The relationship between adherence to a
      Mediterranean diet and the prevalence of metabolic syndrome has been explored in
      cross-sectional studies with discordant results. Two prospective studies with a
      follow up of 6 and 7.5 years show that subjects with the highest adherence to a
      Mediterranean diet had lower cumulative incidence of metabolic syndrome than
      those with the lowest adherence. Two interventional trials document a positive
      effect of a Mediterranean diet on reversal of metabolic syndrome. The
      Mediterranean diet may be also useful to ameliorate liver function tests in obese
      patients with insulin resistance and diabetes. There is no consensus as to what
      diet is the optimal one for patients who have the metabolic syndrome. A
      Mediterranean diet that is moderately lower in carbohydrate (45%), and moderately
      higher in fat (35-40%), with less than 10% of saturated fat, may be beneficial
      for ameliorating features of the metabolic syndrome, including effects on insulin
      sensitivity, blood lipids, and liver function.

PMID- 20158446
TI  - Prevalence and determinants of hyperuricemia in middle-aged, urban Chinese men.
AB  - BACKGROUND: Hyperuricemia is associated with metabolic syndrome and has emerged
      as a marker for both type 2 diabetes and cardiovascular disease. We estimated the
      prevalence and lifestyle risk factors of hyperuricemia in middle-aged, urban
      Chinese men. METHODS: The study included 3,978 urban Chinese men 40-74 years of
      age from a population-based cohort study, the Shanghai Men's Health Study, who
      were free of type 2 diabetes at baseline and had provided fasting blood samples.
      Uric acid concentrations were measured by the uricase method. Hyperuricemia was
      defined as >7.0 mg/dL. Anthropometric measurements and information on lifestyle
      factors and disease history were collected by in-person interviews. RESULTS: One
      quarter of the study subjects had hyperuricemia. Participants with metabolic
      syndrome had a higher prevalence of hyperuricemia. Body mass index (BMI), waist
      to-hip ratio (WHR), waist circumference, and weight gain (since age 20) were
      positively associated with the prevalence of hyperuricemia. Physical activity was
      inversely related to the prevalence of hyperuricemia. The odds ratios for
      hyperuricemia for quintiles of nonoccupational physical activity were 1.00, 0.80,
      0.73, 0.75, and 0.57 (P trend <0.001). Participants with hyperuricemia were less
      likely to be current smokers, but were more likely to drink alcohol regularly.
      Beer consumption was associated with higher risk of hyperuricemia compared with
      consumption of wine or liquor. CONCLUSIONS: In this representative sample of
      middle-aged, urban Chinese men, hyperuricemia is highly prevalent. Obesity,
      weight gain in adulthood, and alcohol intake were associated with a higher
      prevalence of hyperuricemia, whereas daily physical activity and smoking were
      inversely related to the prevalence of hyperuricemia.

PMID- 20158448
TI  - Dietary glycemic index and glycemic load are associated with metabolic control in
      type 2 diabetes: The CAPRI experience.
AB  - BACKGROUND: The role of low-glycemic-index diets in the treatment of diabetes
      mellitus remains unclear. The aim of the present study was to evaluate the
      association between the dietary glycemic index (GI) and glycemic load (GL) with
      metabolic control in type 2 diabetic patients. METHODS: We conducted a cross
      sectional analysis in 901 outpatients with type 2 diabetes attending diabetes
      clinics located in the area of the Campania County, South Italy, who provided
      complete home blood glucose profiles and centralized glycosylated hemoglobin A1c
      (HbA1c). Dietary information was obtained using semiquantitative food-frequency
      questionnaires. HbA1c was assessed in the centralized laboratory while blood
      glucose profiles were assessed at home. RESULTS: After adjustment for age, body
      mass index (BMI), waist circumference, waist-to-hip ratio, smoking, alcohol
      consumption, physical activity, medication use, prevalence of metabolic syndrome,
      hypertension, energy and fiber intake, dietary GI and GL were positively
      associated with HbA1c in a dose-dependent fashion (P for trend, 0.007 for GI and
      0.02 for GL). Diabetic patients with the highest GI and GL had the highest HbA1c
      levels (difference 1%, P = 0.001). The difference in 1-h postmeal glucose levels
      at home between the highest and the lowest quintile of GI was 37 (15) [mean and
      standard deviation (SD)] mg/dL (P = 0.001). CONCLUSIONS: Diets low in GI and GL
      are associated with lower HbA1c and postmeal glucose levels in the everyday life
      of type 2 diabetic patients.

PMID- 20158453
TI  - Structure of the prion protein and its gene: an analysis using bioinformatics and
      computer simulation.
AB  - Prion protein (PrP) gene encodes cellular PrP (PrPC), a
      glycosylphosphatidylinositol (GPI)-anchored cell membrane protein indispensable
      for infections of prion, which causes Creutzfeldt-Jakob disease (CJD) in humans,
      bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep. Although
      PrPC is known to be converted into an abnormal isoform (PrPSc) upon prion
      infection and play an important role in prion diseases, the mechanisms involved
      remain unclear, partly due to the insolubility of PrPSc, which prevents
      experimental biochemical and biophysical analyses. Recently, with improvements in
      computer power and methods, computer analyses have been contributing more to
      prion studies. A comparison of PrP gene sequences revealed mutations and
      polymorphisms in the open reading frame (ORF) of the human PrP gene related to
      prion diseases. In contrast, little mutations or polymorphisms related to
      susceptibility to BSE were found in the ORF of the bovine PrP gene, though
      relationships between insertion/deletion (Ins/Del) polymorphisms of the PrP gene
      promoter and susceptibility to BSE have been found. Our results have shown that
      the specific protein 1 (Sp1) plays important role in the activity of PrP gene
      promoter, which is influenced by polymorphisms in the Sp1 binding sites. The
      potential structural dynamics of PrP have been simulated by computational methods
      such as molecular dynamics (MD) and quantum mechanics (QM). The proposed
      mechanisms of conversion have revealed new insights in prion diseases. In this
      review, we will introduce the gene structure, polymorphisms, and potential
      structural dynamics of PrP revealed by basic and advanced computational analyses.
      The possible contribution of these methods to elucidation of the pathogenicity of
      prion diseases and functions of PrPC is discussed.

PMID- 20158454
TI  - Ubisol-Aqua: coenzyme Q10 prevents antiretroviral toxic neuropathy in an in vitro
      model.
AB  - BACKGROUND: Peripheral neuropathy is the dose-limiting toxicity of stavudine and
      didanosine (nucleoside analogs used in HIV treatment) and is attributed to
      mitochondrial toxicity from these drugs. Acetyl L-carnitine (ALC) and co-enzyme
      Q(10) are proposed as neuropathy treatments, but evidence to support these is
      limited. METHODS: We examined ALC and a water-soluble formulation of co-enzyme
      Q(10) (H(Q)O) for the prevention of d4T and ddI neurotoxicity using cultured
      fetal rat DRG as an in vitro model. RESULTS: DdI (33microM) and d4T (50microM)
      caused clear toxicity (impaired neurite growth) by day 8 of DRG culture. H(Q)O at
      concentrations 1-100microM completely prevented the toxicity of 33microM ddI in
      vitro and ALC at concentrations 1-100 microM substantially (but incompletely)
      prevented ddI toxicity in this model. In contrast, ALC was ineffective at all
      concentrations tested for preventing the toxicity of 50microM d4T. H(Q)O showed
      dose-dependent efficacy for preventing d4T toxicity. H(Q)O (1microM) partially
      prevented d4T toxicity while 10 and 100microM H(Q)O completely prevented d4T
      toxicity in this model. CONCLUSIONS: We find H(Q)O is superior to ALC for
      preventing the neurotoxicity of d4T (the HIV treatment most associated with
      neuropathy) and ddI in vitro. Further study is needed to clarify any clinical
      role for co-enzyme Q(10) co-administration with d4T and ddI and to assess whether
      this compound may have a role in treating established cases of neuropathy.

PMID- 20158456
TI  - A highly concentrated and taste-improved aqueous formulation of efavirenz for a
      more appropriate pediatric management of the anti-HIV therapy.
AB  - Pediatric HIV is scarce in developed countries; 90% of pediatric HIV patients are
      in developing countries. In contrast, children represent 15% of the new
      infections in poor countries. Approximately 90% of the HIV-positive children do
      not have access to antiretrovirals (ARVs). Without treatment, 50% of the patients
      die before the 2 years of age. Efavirenz (EFV, aqueous solubility approximately 4
      microg/mL, 40-45% bioavailability), a non-nucleoside reverse transcriptase
      inhibitor (NNRTI), is a first-choice pediatric ARV. To assure therapeutic plasma
      concentrations, the low oral bioavailability demands the administration of
      relatively high EFV doses. Aqueous EFV irritates the oral mucosa, causing a
      Burning Mouth Syndrome (BMS). A triglyceride-based liquid formulation of EFV (30
      mg/mL) is not commercially available worldwide, making the appropriate dose
      adjustment and the swallowing difficult. More importantly, clinical trials
      indicated that the oral bioavailability of this oily solution is lower than that
      of the solid one. Moreover, a relatively high inter-subject variability has been
      found. The present work reports the development and full characterization of a
      concentrated (20 mg/mL, 2%) and taste-masked aqueous formulation of EFV for a
      more appropriate management of the pediatric anti-HIV therapy. Formulations
      displayed high physicochemical stability over time under regular storage
      conditions. Release assays in vitro showed a burst effect (2 h) and zero-order
      kinetics later on (between 2 and 24 h), compatible with the oral administration
      route and release. Finally, taste tests performed by adult healthy volunteers
      indicated that the unique combination of flavors and sweeteners employed (i)
      reduced the intensity of the BMS and (ii) shortened its duration significantly.
      Overall results indicate that the cost-effective and scalable nanotechnological
      strategy proposed could enable the more convenient and compliant administration
      of lower EFV doses. Due to a better pharmacokinetic profile, this would result in
      similar plasma levels than higher doses administered in solid or triglyceride
      soluble form. In this context, some reduction of the treatment cost can be
      envisioned. This could improve the access of less affluent pediatric patients to
      medication in poor countries.

PMID- 20158455
TI  - Determinants of smoking cessation attempts among HIV-infected patients results
      from a hospital-based prospective cohort.
AB  - BACKGROUND: Non-acquired immune-deficiency syndrome (AIDS) defining malignancies
      (especially lung cancer) and bacterial infections as well as cardiovascular
      diseases now account for almost one third of deaths and morbid events in treated
      patients infected by the Human Immunodeficiency Virus (HIV). Tobacco smoking is a
      major modifiable risk factor of these emergent conditions and almost half of
      these patients are regular smokers in resource-rich countries. OBJECTIVE: To
      estimate the effect of HIV infection characteristics on smoking cessation
      attempts among HIV-infected smokers. METHODS: All smokers of the ANRS CO3
      Aquitaine Cohort with at least two visits between 2000 and 2005 were included in
      this analysis. The probability of smoking cessation attempts was estimated using
      survival analyses for recurrent events (frailty model). Covariates were CD4 cell
      count, gender, age, HIV transmission categories, duration since HIV-diagnosis,
      AIDS stage, antiretroviral therapy, and cardiovascular history. RESULTS: Among
      2223 smokers, 743 attempted to quit smoking at least once. The incidence of
      smoking cessation attempt was lower among patients infected through injection
      drug use (IDU) and was higher among patients aged 50 or older (HR=1.4), those
      with a known duration of HIV infection >15 years (HR=1.5), and those who had
      already tried to quit smoking once (HR=4.2) or more (HR=5.8). DISCUSSION:
      Traditional characteristics associated with smoking cessation attempts are the
      most important to explain smoking cessation attempts in HIV-infected patients.
      These results indicate that strategies successfully implemented in other
      populations should be reinforced to fit the needs of HIV-infected patients.

PMID- 20158457
TI  - Psychological predictors of high-risk sexual behaviour and drug use among
      adolescents in Georgia.
AB  - OBJECTIVES: We tested the association between specific values and beliefs,
      cultural representations of HIV/AIDS and high-risk sexual and drug-use behaviours
      in the Former Soviet Republic of Georgia. METHODS: We questioned 2880 adolescents
      aged 14-17 in Georgia using a three-stage stratified probability sample.
      Respondents were from nine regions sampled across the country. Participants
      completed an inventory measuring demographic variables and openness to change
      values, fatalism, specific societal beliefs, sexual contact, drug taking and
      condom use. RESULTS: Sexual intercourse was reported by 40% of males, 3% of
      females; drug injection by 4% males, 1% of females. Those living in urban
      locations were more likely to report having had sex, have used condoms regularly,
      and tried non-injection drugs. In multivariate logistic analyses, openness to
      change values were associated with having had sex, and fatalistic beliefs with
      having had sex, irregular condom use and drug injection. Particular beliefs (e.g.
      that "mainly gay people get AIDS") were associated with irregular condom use and
      a greater likelihood of drug injection. CONCLUSIONS: Location and specific values
      and beliefs are important risk factors for increased sexual risk-taking and drug
      use amongst adolescents in Georgia.

PMID- 20158458
TI  - Oxaliplatin based chemotherapy and concomitant highly active antiretroviral
      therapy in the treatment of 24 patients with colorectal cancer and HIV infection.
AB  - BACKGROUND: Although FOLFOX4 is considered the standard chemotherapy regimen for
      colorectal cancer (CRC), few data are available on its results in human
      immunodeficiency (HIV)-related CRC. The results were analyzed to evaluate
      feasibility and activity of FOLFOX4 plus highly active antiretroviral therapy
      (HAART) in metastatic CRC (mCRC) HIV-seropositive patients. PATIENTS AND METHODS:
      From January 2002 to March 2007, 24 patients were selected among the CRC HIV
      seropositive patients treated with FOLFOX4 and concomitant HAART within the
      Italian Cooperative Group on AIDS and Tumors (GICAT). RESULTS: Four median cycles
      of chemotherapy were administered; the most common severe toxicity was
      neutropenia (37.5%). An overall response rate of 50% was observed; 4.2% of
      patients achieved complete response and 45.8% partial response. No opportunistic
      infections occurred during or immediately after chemotherapy. The median CD4+
      count was 380 (range 220-570) at diagnosis. CONCLUSIONS: To our knowledge, this
      is the largest study describing activity and tolerability of FOLFOX4 and HAART,
      in this setting. FOLFOX4 plus concomitant HAART resulted feasible and active also
      in HIV-seropositive patients. Moreover, the concomitant use of HAART did not to
      seem to increase the FOLFOX4 toxicity. This study suggests the good tolerability
      of the FOLFOX4, making it a reasonable option for combination with HAART.

PMID- 20158459
TI  - Comparison of the expression and immunogenicity of wild-type and sequence
      modified HIV-1 gag genes in a recombinant Sendai virus vector.
AB  - Efficient expression of HIV-1 structural gene involves regulation by viral Rev
      and Rev-responsive elements (RRE). Messenger RNAs of wild-type HIV-1 structural
      genes are either retained in the nucleus or degraded rapidly in the absence of
      Rev/RRE; therefore little protein can be expressed. Modifying HIV-1 genes is an
      excellent approach to circumvent this problem, but it is a laborious and costly
      process. Using certain vectors to deliver wild-type genes may be a promising
      approach. In this study, the wild-type and modified gag genes, derived from
      Chinese HIV-1 isolates, were separately constructed in both plasmid DNA and
      recombinant Sendai virus vectors (rSeV). The expression and immunogenicity of the
      wild-type and modified gag genes were compared. The results showed that efficient
      expression of the modified gag gene could be achieved by transfection with DNA
      and infection with rSeV, but the efficient expression of wild-type gag could only
      be achieved by rSeV. In addition, the rSeV expressing wild-type gag elicited
      similar Gag-specific immune responses with modified gag in both SeV/SeV and DNA
      prime/rSeV-boost schemes. However, SeV/SeV failed to produce Gag-specific
      responses as robust as DNA/rSeV. Then the SeV-specific humoral and cellular
      immune responses were evaluated just before the second rSeV vaccine immunization.
      It was found that anti-SeV neutralizing antibody was very low but the SeV
      specific cellular response was strong. Efficient expression of wild-type HIV-1
      structural genes may make the SeV vector a useful tool for the HIV-1 vaccine
      research, but the strong SeV-specific cellular immune responses may impair the
      efficacy of SeV-SeV vaccination scheme.

PMID- 20158460
TI  - Synthesis and in vitro transdermal penetration of methoxypoly(ethylene glycol)
      carbonate and carbamate derivatives of lamivudine (3TC).
AB  - The objective of this study was to determine the in vitro transdermal permeation
      through the human stratum corneum (SC) of the antiretroviral (ARV) drug
      lamivudine (3TC) (1) and its synthesised methoxypoly(ethylene glycol) (MPEG)
      carbamates and carbonates in phosphate buffer solution and with the use of
      Pheroid as delivery system and to establish a relationship, if any, with selected
      physicochemical properties. The synthesis and in vitro human skin permeation flux
      of three N4-methoxypoly(ethylene glycol) carbamates (3)-(5) and three 6'-O
      methoxypoly(ethylene glycol) carbonates (6)-(8) of lamivudine are reported. The
      derivatives were synthesised in a two-step process by coupling activated MPEG
      oligomers of various chain lengths to either the 4-amino or 6'-hydroxy group of
      lamivudine. Irrespective of the oligomeric series of derivatives (carbamate or
      carbonate), the aqueous solubility increases as the MPEG chain lengthens while
      the solubility in octanol (lipophilicity) remained almost constant. Regardless of
      the mechanism of diffusion viz. passive (in PBS) or use of enhancer (Pheroid), no
      derivative penetrate the skin better than the parent drug itself. The use of
      Pheroid even appeared to significantly retard the skin permeation.

PMID- 20158462
TI  - Human tooth germ stem cells preserve neuro-protective effects after long-term
      cryo-preservation.
AB  - The use of mesenchymal stem cells (MSCs) has been shown to be promising in
      chronic disorders such as diabetes, Alzheimer's dementia, Parkinson's disease,
      spinal cord injury and brain ischemia. Recent studies revealed that human tooth
      germs (hTG) contain MSCs which can be easily isolated, expanded and cryo
      preserved. In this report, we isolated human tooth germ stem cells (hTGSCs) with
      MSC characteristics from third molar tooth germs, cryo-preserved them at -80(
      degrees )C for 6 months, and evaluated for their surface antigens, expression of
      pluri-potency associated genes, differentiation capacity, karyotype, and
      proliferation rate. These characteristics were compared to their non-frozen
      counterparts. In addition, neuro-protective effects of cryo-preserved cells on
      neuro-blastoma SH-SY5Y cells were also assessed after exposure to stress
      conditions induced by hydrogen-peroxide (oxidative stress) and paclitaxel
      (microtubule stabilizing mitotic inhibitor). After long term cryo-preservation
      hTGSCs expressed surface antigens CD29, CD73, CD90, CD105, and CD166, but not
      CD34, CD45 or CD133, which was typical for non-frozen hTGSCs. Cryo-preserved
      hTGSCs were able to differentiate into osteo-, adipo- and neuro-genic cells. They
      also showed normal karyotype after high number of population doublings and
      unchanged proliferation rate. On the other hand, cryo-preserved cells
      demonstrated a tendency for lower level of pluri-potency associated gene
      expression (nanog, oct4, sox2, klf4, c-myc) than non-frozen hTGSCs. hTGSCs
      conditioned media increased survival of SH-SY5Y cells exposed to oxidative stress
      or paclitaxel. These findings confirm that hTGSCs preserve their major
      characteristics and exert neuro-protection after long-term cryo-preservation,
      suggesting that hTGSCs, harvested from young individuals and stored for possible
      use later as they grow old, might be employed in cellular therapy of age-related
      degenerative disorders.

PMID- 20158463
TI  - Interleukin-1beta plays a role in the activation of peripheral leukocytes after
      blood-brain barrier rupture in the course of subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) develops when extravasated arterial blood enters
      subarachnoid space and mixes with cerebrospinal fluid. As a result, many
      pathologies develop, including increase in brain-blood barrier (BBB) permeability
      and activation of peripheral leukocytes, that in turn augments immuno
      inflammatory response, considered as the cause of numerous complications
      following SAH. In the study, we examined the role of one of major cytokines,
      interleukin 1-beta (IL-1beta), in the BBB rupture and subsequent migration of
      leukocytes into central nervous system (CNS) after experimental SAH in adult
      rats. SAH was produced by injection of 150 uL of autologous arterial blood into
      cisterna magna. In 50% of animals, IL-1beta activity was inhibited by
      intracerebroventricular administration of anti-rat IL-1beta antibodies (SAH'
      groups). Control group consisted of sham-operated rats. Ninety minutes or 24 hrs
      following surgery, blood samples were taken, then animals were perfused
      transcardially and whole brains were collected. Three major populations of
      leukocytes present at brain stem and frontal part of the brain - granulocytes,
      monocytes/macrophages and lymphocytes - were labeled with appropriate antibodies.
      S-100B protein concentration in the serum, a marker of BBB permeability, was also
      measured. Neutralization of IL-1beta activity reduced elevated S-100B level and
      number of leukocytes found within the CNS, however these changes were not
      uniformly significant among different subgroups. The results demonstrate an
      important role of IL-1beta in the BBB damage and leukocyte migration into the CNS
      subarachnoid hemorrhage.

PMID- 20158464
TI  - Real time analysis of neurotransmitters in the brain using a micro-electrode
      system.
AB  - Neurotransmitters catechol and dopamine analogy levels are related to the
      systematic nerve activity. This assay was performed using cyclic voltammetry (CV)
      and square wave (SW) stripping voltammetry, while optimization was performed by
      the carbon fiber microelectrode (CFME) with wire-type reference and counter
      electrodes. In the electrolyte solutions, the analytical parameters of catechol
      were as follows: 8.5 pH, -0.4 V anodic, 0.3 V cathodic, 15s deposition time, 15
      Hz SW frequency, 25 mV SW amplitude and incremental potential of 4 mV. Under
      optimal conditions, working ranges of 0-50 mgL(-1) CV, 0.01-50 mgL(-1) cathodic,
      1-13 mgL(-1) anodic. The relative standard deviation of 0.02 %, n = 15 using 0.5
      mgL(-1) standard. The detection limit was 4.0 ugL(-1). It can be used for in vivo
      direct analysis. Here, diagnostic applications were performed in the brain
      skeleton of living cells in real time. The developed techniques can be useful for
      nerve control and signal detections.

PMID- 20158465
TI  - Nitric oxide production during cerebral ischemia and reperfusion in eNOS- and
      nNOS-knockout mice.
AB  - The purpose of this study was to clarify the kinetics of nitric oxide (NO)
      induced by either endothelial NO synthase (eNOS) or neuronal NO synthase (nNOS)
      after transient global forebrain ischemia. We investigated NO production and
      ischemic changes to hippocampal CA1 neurons in eNOS knockout (-/-) mice and nNOS
      (-/-) mice during cerebral ischemia and reperfusion. NO production was
      continuously monitored by in vivo microdialysis. Global forebrain ischemia was
      produced by occlusion of both common carotid arteries for 10 minutes. Levels of
      nitrite (NO(2)(-)) and nitrate (NO(3)(-)), as NO metabolites, in dialysate were
      determined using the Griess reaction. Two hours after the start of reperfusion,
      animals were perfused with 4% paraformaldehyde. Hippocampal CA1 neurons were
      divided into three phases (severely ischemic, moderately ischemic, surviving),
      and the ratio of surviving neurons to degenerated neurons was calculated as the
      survival rate. The relative cerebral blood flow (rCBF) was significantly higher
      in nNOS (-/-) mice than in control mice after reperfusion. Levels of NO(3)(-)
      were significantly lower in eNOS (-/-) mice and nNOS (-/-) mice than in control
      mice during ischemia and reperfusion. NO(3)(-) levels were significantly lower in
      nNOS (-/-) mice than in eNOS (-/-) mice after the start of reperfusion. Survival
      rate tended to be higher in nNOS (-/-) mice than in control mice, but not
      significantly. These in vivo data suggest that NO production in the striatum
      after reperfusion is closely related to activities of both nNOS and eNOS, and is
      mainly related to nNOS following reperfusion.

PMID- 20158466
TI  - Iron leads to memory impairment that is associated with a decrease in
      acetylcholinesterase pathways.
AB  - Increasing evidence indicates that excessive iron in selective regions of the
      brain may be involved in the etiology of neurodegenerative disorders.
      Accordingly, increased levels of iron have been described in brain regions of
      patients in Parkinson's and Alzheimer's diseases. We have characterized neonatal
      iron loading in rodents as a novel experimental model that mimics the brain iron
      accumulation observed in patients with neurodegenerative diseases and produces
      severe cognitive impairment in the adulthood. In the present study we have
      investigated the involvement of the cholinergic system on iron-induced memory
      impairment. The effects of a single administration of the acetylcholinesterase
      (AChE) inhibitor galantamine or the muscarinic receptor agonist oxotremorine on
      iron-induced memory deficits in rats were examined. Male Wistar rats received
      vehicle or iron (10.0 mg/kg) orally at postnatal days 12 to 14. At the age of 2-3
      months, animals were trained in a novel object recognition task. Iron-treated
      rats showed long-term impairments in recognition memory. The impairing effect was
      reversed by systemic administration of galantamine (1 mg/kg) immediately after
      training. In addition, iron-treated rats that received oxotremorine (0.5 mg/kg)
      showed enhanced memory retention. Rats given iron showed a decreased AChE
      activity in the striatum when compared to controls. The results suggest that, at
      least in part, iron-induced cognitive deficits are related to a dysfunction of
      cholinergic neural transmission in the brain. These findings might have
      implications for the development of novel therapeutic strategies aimed at
      ameliorating cognitive decline associated with neurodegenerative disorders.

PMID- 20158467
TI  - Characterization of endogenous neural progenitor cells after experimental
      ischemic stroke.
AB  - Neural progenitors cells are capable of promoting neurogenesis after ischemic
      stroke in the adult mammalian brain; however the function of these cells and
      their fate is still not clear. Therefore the purpose of this study investigated
      the relationship between neural progenitors and reactive astrocytes after middle
      cerebral artery occlusion (MCAO). Brain infarction was induced by occlusion of a
      right cerebral artery in male Wistar rats. The fate of progenitor cells and the
      surrounding cells was investigated by immunochemical staining for nestin,
      vimentin and glial fibrillary acidic protein (GFAP) positive cells at several
      locations. Vimentin and nestin positive cells were observed in the ipsilateral
      subventricular zone (SVZ), striatum, and cortex at 3 and 7 days after MCAO, but
      those cells were not found at 28 days after ischemia. In contrast, reactive
      astrocyte positive cells increased following MCAO. These reactive astrocytes
      induced astrocytes differentiation of progenitor cells and formed dense
      astroglioses surrounding the ischemic lesion. Reactive astrocytes are thought to
      protect the penumbra during brain ischemia. We examined which brain cell
      expressed nestin and GFAP in the ipsilateral co-expression at 7 days after MCAO,
      especially at the core of injury. These results suggest that robust reactive
      astrocytes after MCAO were possibly differentiation from the induced nestin
      positive cells after early ischemia.

PMID- 20158468
TI  - Haptoglobin phenotype correlates with the extent of cerebral deep white matter
      lesions in hypertensive patients.
AB  - Cerebral white matter lesions (WMLs), due to small vessel disease, can be
      regarded as an early "silent" sign of hypertensive cerebral end-organ damage. As
      haptoglobin (Hp) phenotype has earlier been associated with symptomatic vascular
      disease, we now examined the relationship between Hp phenotype and asymptomatic
      cerebral small vessel disease, manifested by deep and periventricular WMLs, in
      hypertensive patients. We determined Hp phenotype using starch gel
      electrophoresis in 152 hypertensive patients without symptomatic vascular
      disease. We found 26 (17.1%) Hp1-1, 89 (58.6%) Hp2-1 and 37 (24.3%) Hp2-2.
      Volumes of deep and periventricular WMLs were quantitatively measured on brain MR
      images. Patients were ranked in 5 categories according to ascending WMLs volumes.
      Compared to Hp2-2, Hp1-1 was associated with larger deep WMLs volumes when
      adjusted for age, gender, brain volume, 24-hour mean arterial pressure, duration
      of hypertension and previous antihypertensive treatment (ordinal regression
      analysis, OR 2.77, 95%CI 1.08-7.11, p=0.034). No association was found between Hp
      phenotype and periventricular WMLs. Hp1-1 phenotype correlates with the extent of
      hypertensive deep white matter damage. One of the possibilities is that this is
      related to lower regenerating power against endothelial injury in Hp1-1
      individuals.

PMID- 20158469
TI  - Bioabsorbable coronary stents--are these the next big thing in coronary
      angioplasty?
AB  - The role of percutaneous coronary intervention (PCI) in the treatment of coronary
      artery disease has grown at an astronomical pace. Drug eluting stents (DES) offer
      advantages over bare metal stents (BMS) such as reduction in early in-stent
      restenosis rates. However, they have disadvantages like from increased late stent
      thrombosis when compared with BMS. Furthermore, recent data suggest endothelial
      dysfunction in the DES stented segments of the arteries. Currently, bioabsorbable
      stents are under development to avert the complications of DES such as stent
      thrombosis via degradation of the stent over time. The hypothetical advantage of
      leaving behind a natural vessel and restoring vasoreactivity may be the almost
      normal physiology which can be achieved after an intervention with a stent. The
      ABSORB and the PROGRESS AMS are two of the recent clinical trials that have
      looked at the outcomes of using bioabsorbable stents. So far, data from these and
      other studies has yielded mixed results in terms of angiographic and clinical
      outcomes. Newer stents such as REVA and WHISPER are presently being tested in
      preclinical and clinical trials. The landscape for bioabsorbable stents is
      constantly evolving through continued improvisation on existing technology and
      emergence of new technology. Large scale randomized trials are still needed with
      adequate long term follow-up for safety and benefits to have mainstream
      application in coronary artery disease, bioabsorbable stents are a promising
      innovation in the field of PCI. We review some of the patents and the data that
      is emerging on bioabsorbable stents in addition to currently ongoing clinical
      trials.

PMID- 20158461
TI  - Diabetes mellitus: channeling care through cellular discovery.
AB  - Diabetes mellitus (DM) impacts a significant portion of the world's population
      and care for this disorder places an economic burden on the gross domestic
      product for any particular country. Furthermore, both Type 1 and Type 2 DM are
      becoming increasingly prevalent and there is increased incidence of impaired
      glucose tolerance in the young. The complications of DM are protean and can
      involve multiple systems throughout the body that are susceptible to the
      detrimental effects of oxidative stress and apoptotic cell injury. For these
      reasons, innovative strategies are necessary for the implementation of new
      treatments for DM that are generated through the further understanding of
      cellular pathways that govern the pathological consequences of DM. In particular,
      both the precursor for the coenzyme beta-nicotinamide adenine dinucleotide
      (NAD(+)), nicotinamide, and the growth factor erythropoietin offer novel
      platforms for drug discovery that involve cellular metabolic homeostasis and
      inflammatory cell control. Interestingly, these agents and their tightly
      associated pathways that consist of cell cycle regulation, protein kinase B,
      forkhead transcription factors, and Wnt signaling also function in a broader
      sense as biomarkers for disease onset and progression.

PMID- 20158470
TI  - Listeria monocytogenes as a vector for anti-cancer therapies.
AB  - The intracellular pathogen Listeria monocytogenes represents a promising
      therapeutic vector for the delivery of DNA, RNA or protein to cancer cells or to
      prime immune responses against tumour-specific antigens. A number of biological
      properties make L. monocytogenes a promising platform for development as a vector
      for either gene therapy or as an anti-cancer vaccine vector. L. monocytogenes is
      particularly efficient in mediating internalization into host cells. Once inside
      cells, the bacterium produces specific virulence factors which lyse the vaculolar
      membrane and allow escape into the cytoplasm. Once in the cytosol, L.
      monocytogenes is capable of actin-based motility and cell-to-cell spread without
      an extracellular phase. The cytoplasmic location of L. monocytogenes is
      significant as this potentiates entry of antigens into the MHC Class I antigen
      processing pathway leading to priming of specific CD8(+) T cell responses. The
      cytoplasmic location is also beneficial for the delivery of DNA (bactofection) by
      L. monocytogenes whilst cell-to-cell spread may facilitate access of the vector
      to cells throughout the tumour. Several preclinical studies have demonstrated the
      ability of L. monocytogenes for intracellular gene or protein delivery in vitro
      and in vivo, and this vector has also displayed safety and efficacy in clinical
      trial. Here, we review the features of the L. monocytogenes host-pathogen
      interaction that make this bacterium such an attractive candidate with which to
      induce appropriate therapeutic responses. We focus primarily upon work that has
      led to attenuation of the pathogen, demonstrated DNA, RNA or protein delivery to
      tumour cells as well as research that shows the efficacy of L. monocytogenes as a
      vector for tumour-specific vaccine delivery.

PMID- 20158471
TI  - Clostridial spores to treat solid tumours - potential for a new therapeutic
      modality.
AB  - In the quest to developing novel cancer therapies, oncolytic Clostridia are re
      emerging as promising candidates due to their ability to specifically target and
      lyse tumours with great efficacy. Clostridial spores have the innate abilities
      that exploit the unique tumour microenvironment by directly penetrating,
      colonising and killing tumour cells. These unique features have prompted many
      studies to investigate their oncolytic potency. In addition, Clostridia possess a
      number of characteristics that enable them to be developed as oncolytic gene
      delivery vectors, such as their unlimited capacity, antibiotic sensitivity, and
      extracellular existence. Similarly, numerous strategies are being devised and
      tested to take advantage of these features with modern molecular technologies. In
      this review, we detail the traits that distinguish Clostridia from other agents,
      and describe the potential therapeutic effects that Clostridial spores
      demonstrate, but are not achievable with other treatment modalities. Furthermore,
      we will also summarize the recent advances in the use of Clostridial spores as
      viable therapeutic candidates, incorporating the latest progresses in genetic
      engineering tools, such as ClosTron. Finally, we will highlight some avenues
      deserving further studies in order to realise the ultimate goal of utilizing
      oncolytic Clostridia clinically in patients.

PMID- 20158472
TI  - New and bioactive natural products isolated from madagascar plants and marine
      organisms.
AB  - Madagascar, the world's fourth biggest island has an unique biodiversity. The
      interest on the phytochemical investigation of Malagasy plants and marine natural
      products started from the isolation of the potent anti-cancerous bisindole
      alkaloids: vinblastine and vincristine. In this paper, works published in the
      last two decades (1991-2009) on 270 new natural products isolated from Madagascar
      higher plants, liverworts and marine organisms are reviewed. Several results on
      the bioassays of the isolated new natural products have been reported.

PMID- 20158474
TI  - Computational modeling of structure-function of g protein-coupled receptors with
      applications for drug design.
AB  - G protein-coupled receptors (GPCRs) mediate senses such as odor, taste, vision,
      and pain in mammals. In addition, important cell recognition and communication
      processes often involve GPCRs. Many diseases involve malfunction of GPCRs, making
      them important targets for drug development. Indeed, greater than 50 % of all
      marketed therapeutics act on those receptors. Unfortunately, the atomic-level
      structures are only available for rhodopsin, beta2AR, beta1AR, A2A adenosin and
      opsin. In silico computational methods, employing receptor-based modeling, offer
      a rational approach in the design of drugs targeting GPCRs. These approaches can
      be used to understand receptor selectivity and species specificity of drugs that
      interact with GPCRs. This review gives an overview of current computational
      approaches to GPCR model building; ligand-receptor interaction for drug design;
      and molecular mechanism of GPCR activation from simulation.

PMID- 20158473
TI  - Epoxyeicosatrienoic acid analogs and vascular function.
AB  - Arachidonic acid metabolites, eicosanoids, are key contributors to vascular
      function and improper eicosanoid regulation contributes to the progression of
      cardiovascular diseases. Epoxyeicosatrienoic acids (EETs) are synthesized from
      arachidonic acid by epoxygenase enzymes to four regioisomers, 5,6-EET, 8,9-EET,
      11,12-EET, and 14,15-EET. These EETs have interesting beneficial effects like
      vasodilation, anti-inflammation, and anti-platelet aggregation that could combat
      cardiovascular diseases. There is mounting evidence that each regioisomeric EET
      may have unique vascular effects and that the contribution of individual EETs to
      vascular function differs from organ to organ. Over the past decade EET analogs
      and antagonists have been synthesized to determine EET structure function
      relationships and define the contribution of each regioisomeric EET. A number of
      studies have demonstrated that EET analogs induce vasodilation, lower blood
      pressure and decrease inflammation. EET antagonists have also been used to
      demonstrate that endogenous EETs contribute importantly to cardiovascular
      function. This review will discuss EET synthesis, regulation and physiological
      roles in the cardiovascular system. Next we will focus on the development of EET
      analogs and what has been learned about their contribution to vascular function.
      Finally, the development of EET antagonists and how these have been utilized to
      determine the cardiovascular actions of endogenous epoxides will be discussed.
      Overall, this review will highlight the important knowledge garnered by the
      development of EET analogs and their possible value in the treatment of
      cardiovascular diseases.

PMID- 20158475
TI  - Virulence mechanisms displayed by Salmonella to impair dendritic cell function.
AB  - Dendritic cells (DCs) link innate and adaptive immunity by directly recognizing
      pathogen-associated molecular patterns (PAMPs) on bacteria. DCs can capture and
      degrade bacteria and present their antigens on MHC molecules to T cells. PAMP
      recognition promotes DC maturation, a phenotypic change that empowers them to
      prime naive T cells. As a result, an adaptive immune response that specifically
      targets bacteria-derived antigens is initiated. Consequently, any impairment of
      DC function might contribute to bacterial survival and dissemination in the host.
      Therefore, the characterization of DC-bacteria interactions is required to
      understand the mechanisms used by virulent bacteria to avoid adaptive immunity.
      An example of a bacterial pathogen capable of interfering with DC function is
      Salmonella enterica serovar Typhimurium (S. Typhimurium), which causes a typhoid
      like disease in mice. Virulent strains of S. Typhimurium are able to
      differentially modulate the entrance to DCs and avoid lysosomal degradation, to
      prevent antigen presentation on MHC molecules. These features of virulent S.
      Typhimurium are controlled by virulence factors encoded by Salmonella
      Pathogenicity Islands 1 and 2. Modulation of DC functions by the activity of
      these gene products is supported by several recent studies, which have shown that
      pathogenesis might depend on this attribute of virulent S. Typhimurium. Here we
      discuss recent data showing that several virulence factors from Salmonella are
      required to differentially modulate DC function and adaptive immunity in the
      host.

PMID- 20158476
TI  - Recent advances on platensimycin: a potential antimicrobial agent.
AB  - Platensimycin, an active metabolite of Streptomyces platensis, was initially
      discovered by a combination of RNA interferin induced gene-silencing and library
      screening to microbial extracts. Platensimycin selectively inhibits beta -
      ketoacyl-acyl carrier protein (ACP) synthase II (FabF) that is recognized as an
      effective broad-spectrum antibiotic against drug-resistant microorganism strains.
      Its novel scaffold and extraordinary antibacterial activity have drawn great
      attentions in recent years. So far, a number of synthetic strategies have been
      explored for the total synthesis of platensimycin. Moreover, many analogues have
      been investigated in terms of structure-activity relationships (SAR). This review
      provides a detailed overview of updated studies on platensimycin, focusing on
      various total and formal synthetic strategies, development of analogues, and the
      structure-activity relationships.

PMID- 20158477
TI  - Recent progress of Src SH2 and SH3 inhibitors as anticancer agents.
AB  - Src family tyrosine kinases (SFKs) play key roles in regulating signal
      transduction in cellular processes. However, hyper-activated SFKs lead to
      uncontrolled cell proliferation and cancers. For both Src SH2 and SH3 domains
      involve in the regulation of tumorigenesis signal pathways, the SH2 and SH3
      inhibition strategies are expected to block the protein-protein interactions
      between SFKs and their corporation proteins to abolish the signal transduction.
      Many inhibitors of SH2 and SH3 domain have been identified. Herein, some
      predominant examples of these inhibitors are reviewed.

PMID- 20158478
TI  - Lipoplexes formulation and optimisation: in vitro transfection studies reveal no
      correlation with in vivo vaccination studies.
AB  - The aim of these studies was to compare the effect of liposome composition on
      physico-chemical characteristics and transfection efficacy of cationic liposomes
      both in vitro and in vivo. Comparison between 4 popularly used cationic lipids,
      showed 3b-N-(dimethylaminoethyl)carbamate (DC-Chol) to promote the highest
      transfect levels in cells in vitro with levels being at least 6 times higher than
      those of 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA). 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP), and dimethyldioctadecylammonium (DDA) and
      approximately twice as efficient as dipalmitoyl-trimethylammonium-propane
      (DPTAP). To establish the role of the helper lipid, DC-Chol liposomes were
      formulated in combination with either 1,2-dioleoyl-sn-glycero-3
      phosphatidylethanolamine (DOPE) or cholesterol (Chol) (1:1 molar ratio) with and
      without the addition of phosphatidyl choline. The choice of helper lipid
      incorporated within the bilayer was found to influence the formation of
      complexes, their resultant structure and their transfection efficiency in vitro,
      with SUV-DNA complexes containing optimum levels of DOPE giving higher
      transfection than those containing cholesterol. The inclusion of PC within the
      formulation also reduced transfection efficiency in vitro. However, when
      administered in vivo, SUV-DNA complexes composed of PC:Chol:DC-Chol at a molar
      ratio of 16:8:4 micromole/ml were the most effective at inducing splenocyte
      proliferation upon exposure to antigen in comparison to control spleens. These
      results demonstrate that there is no in vitro/in vivo correlation between the
      transfection efficacy of these liposome formulations and in vitro transfection in
      the above cell model cannot be taken as a reliable indicator for in vivo efficacy
      of DNA vaccines.

PMID- 20158479
TI  - Ion Exchange Resins Transforming Drug Delivery Systems.
AB  - Ion-exchange resins are light, porous, three-dimensional high molecular weight
      cross -linked matrix of hydrocarbon chains carrying positively or negatively
      charged sites that can attract an ion of opposite charge from the surrounding
      medium. There is stoichiometric exchange of mobile ions between the solid and the
      solution called as Ion-exchange which does not lead to any radical change in the
      properties and structure of the solid. Depending upon the type of Ion-exchanged
      it can be either Cation-exchange or Anion-exchange. They are prepared in the form
      of granules, beads or sheets. As drug delivery systems they have received
      considerable attention after the 1950s due to their inertness, freedom from side
      effects, high drug loading capacity, ease of sterilization and the fact that
      their structure can be easily altered to achieve the desired drug release
      characteristics. Their use is revolutionizing all traditional delivery systems
      namely- oral, nasal, ophthalmic and parenteral. Ion- exchange resins have been
      used for the development of novel drug delivery systems (NDDSs), to modify the
      characteristics of the dosage form and various other biomedical applications. The
      present article deals with the varied applications of ion-exchange resins for
      taste making, as resinates (simple and microencapsulated or coated), Pennkinetic
      systems, in selective recovery of pharmaceuticals, in pH and ionic strength
      responsive systems, in gastro-retentive systems, in hollow fiber systems, as
      sigmoidal release systems, as site specific delivery systems and as
      inotophoretically assisted transdermal drug delivery systems. They also have an
      immense importance when used as disintegrants / superdisintegrants in formulation
      of orodispersible tablets, powder processing aids and in the dissolution and
      stabilization of drugs.

PMID- 20158480
TI  - Preparation and evaluation of isosorbide mononitrate hydrogels for topical
      fissure treatment.
AB  - The aim of the present study was to prepare and evaluate hydrogels containing
      0.1% isosorbide mononitrate (ISMN) for topical treatment of anal fissure. The
      hydrogels were prepared on the base of Carbopol 940, Poloxamer 407 or their
      combination. The highest viscosity and significant thyxotropy were observed for
      the combined hydrogel, which corresponded with slow drug release. Drug release
      from Poloxamer hydrogel was slow probably due to the heterogeneous structure of
      the gel - hydrophobic polyoxypropylene domains and hydrophilic polyoxyethylene
      domains. Drug release form Carbopol hydrogel was faster, which was associated
      with the lower viscosity and homogeneous gel structure. Further, Carbopol gel
      containing 0.1% ISMN (wt/wt) was tested on 21 patients with two applications
      daily for a period of 6 weeks. The results showed that chronic anal fissures
      healed in 71% of the patients. The formulation based on Carbopol seemed to be
      appropriate and efficient for the topical mononitrate treatment of anal fissures.

PMID- 20158481
TI  - 5-Fluorouracil buccal tablets for locoregional chemotherapy of oral squamous cell
      carcinoma: formulation, drug release and histological effects on reconstituted
      human oral epithelium and porcine buccal mucosa.
AB  - 5-Fluorouracil (5-FU) is currently used for treatment of oral squamous cell
      carcinoma (OSCC). 5-FU is given by i.v. although the systemic administration is
      associated with severe toxic effects and no topical formulations of 5-FU for
      buccal drug delivery have been reported. In this study we would report the
      development of buccal tablets suitable for direct application of low-doses of 5
      FU on cancer lesions. The topical administration could be effective on tumor area
      while systemic undesired side effects are avoided. Preliminarily, the limited
      tendency of 5-FU to cross the buccal tissue was established using reconstituted
      human oral epithelium (RHOE, in vitro) and porcine buccal mucosa (ex vivo) as
      mucosal models. The values of steady-state flux and permeability coefficient
      suggested the scarce aptitude of 5-FU to reach the systemic circulation. Matrix
      buccal tablets, were designed for 5-FU local delivery, developed and prepared.
      Release tests showed a highly reproducible Higuchian drug discharge. After tablet
      administration on buccal tissue specimens, the occurrence of histo-morphological
      effects of 5-FU was highlighted. Apoptotic events were registered in all samples
      treated while only negligible amounts of 5-FU permeated the buccal membrane and
      reached the simulated plasma. The results suggest that loaded matrix tablets
      containing 5% of 5-FU could be a useful means in topical treatment of OSCC.

PMID- 20158482
TI  - Novel drug delivery systems for sustained and targeted delivery of anti- cancer
      drugs: current status and future prospects.
AB  - In the past years, alternative pharmaceutical formulations of anti-cancer agents
      have been investigated in order to improve conventional chemotherapy treatment.
      In conventional/current therapy oral tablet, capsule and injectable formulations
      are used for anti-cancer drugs delivery. These formulations associated with
      problems like severe toxic side effects on healthy organs, difficulties in
      clinical administration, drug resistance and limited access of the drug to the
      tumor sites suggested the need to focus on site specific controlled drug delivery
      systems. Novel drug delivery systems are capable of controlling the rate of drug
      delivery, sustaining the duration of therapeutic activity and targeting the drug
      to the disease tissue leading to better therapeutic effect with minimum side
      effects. In this review, we have explored the literature related to recent
      development in delivery of anti-cancer drugs identify problems in present
      conventional chemotherapy and detailed newer approaches and future development in
      the delivery of anti-cancer drugs.

PMID- 20158483
TI  - Studies on Poloxamer Based Mucoadhesive Insitu Ophthalmic Hydrogel of
      Moxifloxacin HCL.
AB  - Conventional eye drops shows relatively low bioavailability due to poor
      precorneal contact time. In situ hydrogels are of great importance in providing
      sustained ocular drug delivery due to their elastic properties hydrogels resist
      ocular drainage leading to longer contact times. In the present study an in situ
      gelling thermoreversible mucoadhesive gel was formulated of an antibacterial
      agent Moxifloxacin HCl using combination of poloxamer 407 and poloxamer 188 with
      different mucoadhesive polymers such as Xanthan gum and Sodium alginate with a
      view to increase in gel strength and bioadhesion force and thereby increase in
      precorneal contact time and there by increase in bioavailability of the drug. The
      formulations were evaluated for physical parameters like Clarity, pH,
      spreadability, drug content, gelation temperature, gel strength, bioadhesion
      force and in vitro drug release study. The formulated gels were transparent,
      uniform in consistency and had spreadability with a pH range of 6.8 to 7.4. A
      satisfactory bioadhesion (3298 to 4130 Dyne/cm(2)) on the sheep's corneal surface
      and good gel strength (95 to 128 sec) were also observed. As the concentration of
      mucoadhesive polymers in the gel formulation increases, the rate of drug release
      decreases. The order of drug release was Xanthan gum>Sodium alginate. It was
      concluded that a thermoreversible in situ gel formulation with Moxifloxacin HCl
      can be formulated by combining with mucoadhesive polymers and can effectively be
      used in safe and sustained ocular drug delivery with greater bioadhesion force
      and gel strength as compared to the thermoreversible polymers poloxamer 407 or
      188 when used alone.

PMID- 20158484
TI  - Synthetic polyacrylate polymers as particulate intranasal vaccine delivery
      systems for the induction of mucosal immune response.
AB  - The nasal route as a site of vaccine delivery for both local and systemic effect
      is currently of considerable interest. The administration of vaccines to mucosal
      surfaces such as the nasopharynx associated lymphoid tissues confers many
      advantages since the nasal mucosa is a primary site through which most inhaled
      antigens are encountered. However, the success of intranasally delivered mucosal
      vaccines is limited by lack of effective vaccine formulations or delivery systems
      suitable for use in humans. This review provides a brief overview of the mucosal
      immune system at the nasal surface, enhancement techniques for induction of
      mucosal immune response after intranasal administration of particulate systems
      and an explanation of the inherent properties of polyacrylate polymer-based
      particulate systems that may facilitate mucosal immune responses.

PMID- 20158485
TI  - Nanotechnology and radiopharmaceuticals: diagnostic and therapeutic approaches.
AB  - Nanotechnology is a novel but rapidly advancing domain of Therapeutics. Nanoscale
      diameter particles such as liposomes and dendrimers may be conscribed for the
      effective and safe administration of several drugs. The main advantages of
      nanosystem-mediated drug delivery are the following; i) sufficient absorption,
      ii) delayed metabolism and excretion, iii) longer half-life, iv) ability to cross
      several anatomical barriers, v) enhanced accumulation in specific target-tissues
      (e.g. malignant tumors), vi) lower toxicity of the drug. During the last years
      there is a growing interest around the potential contribution of Nanotechnology
      in the development of Nuclear Medicine and vice versa. Radioactive agents called
      radiopharmaceuticals are already used in several medical procedures. Exploiting
      their ability to accumulate selectively on specific organ-targets,
      radiopharmaceuticals serve in diagnostic applications, such as scintiscan, PET
      scan and in therapy of several diseases (e.g. thyroid cancer). The use of
      nanosystems may further ameliorate the properties of radiopharmaceuticals
      regarding their targeting ability and their unique pharmacokinetic properties. On
      the other hand radionuclides may serve in experimental studies for the
      pharmacological evaluation of nanosystems. Nevertheless further research is
      required in order to confirm the effectiveness and safety of nanosystem-mediated
      radiopharmaceutical applications.

PMID- 20158486
TI  - Characterization of Peptide Polymer Interactions in Poly(alkylcyanoacrylate)
      Nanoparticles: A Mass Spectrometric Approach.
AB  - Drug/polymer interactions occur during in situ polymerization of
      poly(alkylcyanoacrylate) (PACA) formulations. We have used MALDI ionization
      coupled tandem time-of-flight (TOF) mass spectrometry as an accurate method to
      characterize covalent peptide/polymer interactions of PACA nanoparticles with the
      bioactives D-Lys6-GnRH, insulin, [Asn1-Val5]-angiotensin II, and fragments of
      insulin-like growth factor 1 (IGF-1 (1-3)) and human adrenocorticotropic hormone
      (h-ACTH, (18-39)) at the molecular level. Covalent interactions of peptide with
      alkylcyanoacrylate were identified for D-Lys6-GnRH, [Asn1-Val5]-angiotensin II
      and IGF-1 (1-3). D-Lys6-GnRH and [Asn1-Val5]-angiotensin II were modified at
      their histidine side chain within the peptide, whilst IGF-1 (1-3) was modified at
      the C-terminal glutamic acid residue. The more complex protein insulin was not
      modified despite the presence of 2 histidine residues. This might be explained by
      the engagement of histidine residues in the folding and sterical arrangement of
      insulin under polymerization conditions. As expected, h-ACTH (18-39) that does
      not contain histidine residues did not interfere in the polymerisation process.
      Lowering the pH did not prevent the covalent association of PACA with D-Lys6-GnRH
      or IGF-1 (1-3). Conclusively, protein and peptide bioactives are potentially
      reactive towards alkylcyanoacrylate monomers via various mechanisms with limited
      interference of pH. Histidines and C-terminal glutamic acid residues have been
      identified as potential sites of interaction. The likelihood of their engagement
      in the polymerisation process (initiators), however, seems dependant on their
      sterical availability. The reactivity of nucleophilic functional groups should
      always be considered and bioactives examined for their potential to covalently
      interfere with alkylcyanoacrylate monomers, especially when designing PACA
      delivery systems for protein and peptide biopharmaceuticals.

PMID- 20158487
TI  - Biodistribution and pharmacokinetics of PEG-10kDa-cholecystokinin-10 in rats
      after different routes of administration.
AB  - Cholecystokinin, produced in the proximal small intestine, is a short acting
      satiating peptide hormone. CCK-10, before and after mono-iodination, was
      previously coupled to 10kDa polyethylene glycol (PEG). The formed conjugates
      PEG10kDa-CCK-10 and PEG10kDa-[(127)I]-CCK-10 show after i.p. administration to
      rats a sustained food intake reduction during 8h in comparison to 2h for free CCK
      10. The present study examined the blood pharmacokinetics of this pharmacological
      interesting molecule by means of PEG10kDa-[(123)I]-CCK-10 following intravenous,
      intraperitoneal, intramuscular and nasal administration and the biodistribution
      after i.p. administration. HPLC analysis with radiometric detection allowed the
      differentiation between inorganic iodide and the intact tracer in blood. Blood
      kinetics after i.v. injection was fitted to a bi-exponential with a distribution
      half-life of 15 min and with an elimination half-life of 8 hours for intact
      PEG10kDa-[(123)I]-CCK-10. The biodistribution studies showed a higher
      accumulation of the tracer for all administration routes in organs expressing CCK
      receptors localized in the gastrointestinal tract such as pancreas, duodenum and
      small intestine. No indication of blood brain barrier crossing for the conjugate
      could be observed independently of the administration route. Main clearance was
      via the urinary pathway.

PMID- 20158488
TI  - Dextran carrier macromolecule for colon specific delivery of celecoxib.
AB  - The colon specific polymeric conjugates of celecoxib were prepared with dextran
      of different molecular weight Mr approximately 40 000, 70 000, and 100 000 (CSD
      40, CSD-70 and CSD-100). Succinic acid was used as linker between the drug and
      dextran. The prepared conjugates were characterized by UV, IR, 1H NMR and HPLC.
      The maximum degree of substitution 3.9+/-0.20 % was found with the dextran CSD
      100 conjugates. The percent release of drug obtained by in-vitro hydrolysis
      studies, was found to be 24.37+/- 0.6, 23.0 +/- 0.5 and 20.13+/- 0.8 in simulated
      colonic fluid (SCF) pH 6.8 while 17.90 +/- 0.4, 16.8+/- 0.75 and 15.47 +/- 0.5 in
      simulated intestinal fluid (SIF) pH 7.4 for CSD-40, CSD-70 and CSD-100,
      respectively, in both medium. The drug release from the conjugates was observed
      for 24 h in 3% w/v rat caecal content and found to be 41.77 +/- 1.2, 39.03 +/-
      1.0 and 35.26 +/- 1.09 for CSD-40, CSD-70 and CSD-100 conjugates, respectively.
      The half life of conjugates was determined and was found to be short in 3% w/v
      rat caecal content. No amount of drug was released in simulated gastric fluid pH
      1.2 and stomach homogenate in 2 h. The amount of drug released from small
      intestine homogenate was 3.4+/- 0.1 percent in 12 h for the CSD-40. The above
      result suggests that dextran could be used as a macromolecular carrier for colon
      specific drug delivery of celecoxib.

PMID- 20158489
TI  - Sustained release of verapamil hydrochloride from sodium alginate microcapsules.
AB  - The objective of the present study was to develop sustained release microcapsules
      of verapamil hydrochloride (VH) using biodegradable polymers. For this purpose
      microcapsules embedded verapamil hydrochloride were prepared using sodium
      alginate alone and also by incorporating some co polymers like methyl cellulose
      (MC), sodium carboxy methyl cellulose (SCMC) , poly vinyl pyrollidone (PVP) and
      xanthan gum by employing complex emulsion method of microencapsulation.
      Microcapsules were prepared in various core: coat ratios to know the effect of
      polymer and co polymers on drug release. Overall ten formulations were prepared
      and evaluated for flow behaviour, sieve analysis, drug entrapment efficiency, in
      vitro dissolution studies, stability studies, including scanning electron
      microscopy and DSC. The resulting microcapsules were discrete, large, spherical
      and also free flowing. The drug content in all the batches of microcapsules was
      found to be uniform. The release was depended on core: coat ratio and nature of
      the polymers. FTIR analysis revealed chemical integrity between Verapamil
      hydrochloride (VH), sodium alginate and between the copolymers. Among the four
      copolymers used methyl cellulose retarded the drug release more than the other
      three, hence the same formulation was subjected for in vivo studies. The drug
      release from the microcapsules was found to be following non fickian diffusion.
      Mechanism of drug release was diffusion controlled first order kinetics. Drug
      diffusion co efficient and correlation co efficient were also assessed by using
      various mathematical models. In vivo result analysis of pharmacokinetic
      parameters revealed that t max of reference and test formulations were almost
      same. From the study it was concluded that, sustained release Verapamil hydro
      chloride microcapsules could be achieved with success using sodium alginate alone
      and also in combination with other biodegradable polymers.

PMID- 20158490
TI  - Electroporation: an avenue for transdermal drug delivery.
AB  - The stratum corneum (SC) is a primary rate limiting barrier to permeation of drug
      molecules through the skin. Small molecular weight lipophilic drugs that are
      effective at low doses can be effectively delivered by passive transdermal
      delivery. The SC does not permit passage of polar/hydrophilic and macromolecules.
      Passive and physical penetration enhancements strategies are used to overcome
      this barrier property of the SC. Passive penetration enhancement techniques
      include use of supersaturated solutions and penetration enhancers. In general,
      the drug delivery potential of chemical modalities is limited. Therefore,
      physical permeation enhancement techniques gained a lot of focus in the recent
      past. Physical penetration enhancement techniques include iontophoresis,
      electroporation and sonophoresis. Electroporation utilizes high voltage pulses
      that are applied for a very short time to permeabilize the skin to facilitate
      transport of macromolecules and hydrophilic compounds. Several drugs have been
      administered via this system successfully. This review presents an overview of in
      vitro and in-vivo studies demonstrating therapeutic benefits offered by
      electroporation assisted permeation. Factors affecting electroporation, synergism
      between electroporation and other penetration enhancing strategies are also
      discussed.

PMID- 20158491
TI  - Isolation and physicochemical characterization of Assam Bora rice starch for use
      as a plasma volume expander.
AB  - Water soluble polysaccharides are most effective oncotic agents which are used
      for treatment of intravascular volume deficiency. Nowadays, they are used as
      basic material for plasma volume expander. Plasma volume expander based on starch
      has lower tendency to remain in any major organ of body in comparison to other
      plasma volume expander. Branched component of starch amylopectin is very similar
      in structure to glycogen, the reserve polysaccharides of animal; for all this
      reason starch is compatible with body tissues. Physicochemical properties of raw
      starch and amylopectin, isolated from Assam Bora rice were characterized for use
      as plasma volume expander. Characterization involves the determination of ash
      value, weight average molecular mass, viscosity and resistance towards enzymatic
      (amylase) hydrolysis. Amylose content was almost negligible. The X-ray
      diffraction pattern of Assam Bora rice starch was typically A type. High degree
      of crystallinity of Assam Bora rice starch reflects its resistance towards
      enzymatic hydrolysis which is of therapeutic advantage for using it as a plasma
      volume expander.

PMID- 20158492
TI  - Molecular mechanisms in aging and current strategies to counteract sarcopenia.
AB  - Sarcopenia, the progressive loss of muscle mass with age, is characterized by a
      deterioration of muscle quantity and quality leading to a gradual slowing of
      movement and a decline in strength and power. Sarcopenia is a highly significant
      public health problem. Since these age-related changes in skeletal muscle are
      largely attributed to various molecular mediators affecting fiber size,
      mitochondrial homeostatis, and apoptosis, the mechanisms responsible for these
      deleterious changes present numerous therapeutic targets for drug discovery. We
      and other researchers demonstrated that a disruption of Akt-mTOR and RhoA-SRF
      signaling but not Atrogin-1 or MuRF1 contributes to sarcopenia. In addition,
      sarcopenia seems to include a marked loss of fibers attributable to apoptosis.
      This review deals with molecular mechanisms of muscle atrophy and provides an
      update on current strategies (resistance training, myostatin inhibition,
      treatment with amino acids or testosterone, calorie restriction, etc) for
      counteracting this loss. Resistance training in combination with amino acid
      containing nutrition would be the best candidate to attenuate, prevent, or
      ultimately reverse age-related muscle wasting and weakness.

PMID- 20158493
TI  - The Six Item Cognitive Impairment Test (6-CIT) as a screening test for dementia:
      comparison with Mini-Mental State Examination (MMSE).
AB  - BACKGROUND: The UK national Dementia Strategy clearly outlines a case for early
      detection and diagnosis of dementia. There is thus a need for a brief screening
      test for dementia in primary care, which can be administered and scored easily.
      AIM: To compare the performance of two cognitive scales, Mini-Mental State
      Examination (MMSE) and 6 Item Cognitive Impairment Test (6-CIT), as screening
      test for dementia in a naturalistic setting. METHODS: 209 subjects referred to
      Old Age Psychiatry service were retrospectively studied. Their MMSE and 6-CIT
      scores were used to compare sensitivity, specificity and the Receiver Operating
      Characteristic (ROC) Curves for diagnosis of dementia. RESULTS: The correlation
      between the MMSE score and 6-CIT score is - 0.822. The MMSE has a sensitivity of
      79.7% and specificity of 86.4% (cut-off 23/24). The 6-CIT has a sensitivity and
      specificity of 82.5% and 90.9% respectively (cut-off 10/11). The sensitivity of
      the 6-CIT increases to 90.2% at a lower cut-off of 9/10, but the corresponding
      specificity drops to 83.3%. CONCLUSION: The 6-CIT is a brief and simple test of
      cognition, which correlates reasonably well with the MMSE in a naturalistic
      setting. Compared with the MMSE it performs well as a screening instrument for
      dementia, which makes it a more appropriate test for primary care usage.

PMID- 20158494
TI  - Hospital utilization and aging in Spain (2006).
AB  - OBJECTIVES: The main objective of this study is to verify the existence of a
      direct relation between age, ageing and hospital resources utilization. METHODS:
      For this purpose, we use not only population variables, but also clinical
      parameters such as severity and complexity, as proxy of consumption and hospital
      costs. Through a comprehensive statistical analysis, quantitative variables of
      the Spanish Minimum Data Set of year 2006 (length of stay, relative weight,
      number of diagnoses and procedures) according to age groups and gender, types of
      admission (emergency or scheduled) and discharge (alive or dead), measuring the
      severity by weight, complications, comorbidities and mortality, and complexity by
      weight and length of stay. RESULTS: The highest severity was observed in 65-69
      year-old males and the highest complexity in 75-79 year-old males and 85-89 year
      old females (p<.0001). The severity and complexity are also higher among 65-69
      year-old males and 70-79 year-old patients of both sexes with emergency access
      (p<.0001). The deceased patients are more aged with higher severity and
      complexity than the survivors (p<.0001). CONCLUSIONS: The age per se is not
      directly related to consumption of hospital resources. Therefore, aging does not
      necessarily imply higher consumption or increased hospital costs. Emergency
      admitted in-patients are older and more severe and complex than the scheduled
      ones, thus consuming more resources and implying higher hospital costs; the same
      is true for the deceased versus the survivors.

PMID- 20158495
TI  - Accessing timely rehabilitation services for a global aging society? Exploring
      the realities within Canada's universal health care system.
AB  - The proportion of older persons is increasing in developed and developing
      countries: this aging trend can be viewed as a two-edged sword. On the one hand,
      it represents remarkable successes regarding advances in health care; and on the
      other hand, it represents a considerable challenge for health systems to meet
      growing demand. A growing disequilibrium between supply and demand may be
      particularly challenging within publicly funding health systems that 'guarantee'
      services to eligible populations. Rehabilitation, including physical therapy, is
      a service that if provided in a timely manner, can maximize function and mobility
      for older persons, which may in turn optimize efficiency and effectiveness of
      overall health care systems. However, physical therapy services are not
      considered an insured service under the legislative framework of the Canadian
      health system, and as such, a complex public/private mix of funding and delivery
      has emerged. In this article, we explore the consequences of a public/private mix
      of physical therapy on timely access to services, and use the World Health
      Organization (WHO) health system performance framework to assess the extent to
      which the emerging system influences the goal of aggregated and equitable health.
      Overall, we argue that a shift to a public/private mix may not have positive
      influences at the population level, and that innovative approaches to deliver
      services would be desirable to strengthening rather than weaken the publicly
      funded system. We signal that strategies aimed at scaling up rehabilitation
      interventions are required in order to improve health outcomes in an evolving
      global aging society.

PMID- 20158496
TI  - Uncoupling protein-2 and the potential link between metabolism and longevity.
AB  - The discovery of novel uncoupling proteins (UCP2 and UCP3) over 10 years ago
      heralded a new era of research in mitochondrial uncoupling in a diverse range of
      tissues. Despite the research vigor, debate stills surrounds the exact function
      of these uncoupling proteins. For example, the level of uncoupling, the mechanism
      and mode of action are all under-appreciated at this point in time. Our recent
      work has used genetic mouse models to focus on the physiological relevance of
      UCP2. We have used these mouse models to better appreciate the role UCP2 in human
      health and disease. In this review we focus on new research showing that UCP2
      promotes longevity by shifting a given cell towards fatty acid fuel utilization.
      This metabolic hypothesis underlying UCP2-dependent longevity suggests that UCP2
      is critically positioned to maintain fatty acid oxidation and restrict subsequent
      oxidative damage allowing sustained mitochondrial oxidative capacity and
      mitochondrial biogenesis. These mechanisms converge within the cell to boost cell
      function and metabolism and the net result promotes healthy aging and increased
      lifespan. Finally, UCP2 is a useful dietary and therapeutic target to promote
      lifespan and is an important mitochondrial protein connecting longevity to
      metabolism.

PMID- 20158497
TI  - The central role of macrophages in trypanosomiasis-associated anemia: rationale
      for therapeutical approaches.
AB  - Bovine African trypanosomiasis causes severe economical problems on the African
      continent and one of the most prominent immunopathological parameters associated
      with this parasitic infection is anemia. In this report we review the current
      knowledge of the mechanisms underlying trypanosomiasis-associated anemia. In
      first instance, the central role of macrophages and particularly their activation
      state in determining the outcome of the disease (i.e. trypanosusceptibility
      versus trypanotolerance) will be discussed. In essence, while persistence of
      classically activated macrophages (M1) contributes to anemia development,
      switching towards alternatively activated macrophages (M2) alleviates pathology
      including anemia. Secondly, while parasite-derived glycolipids such as the
      glycosylphosphatidylinositol (GPI) induce M1, host-derived IL-10 blocks M1
      mediated inflammation, promotes M2 development and prevents anemia development.
      In this context, strategies aimed at inducing the M1 to M2 switch, such as GPI
      based treatment, adenoviral delivery of IL-10 and induction of IL-10 producing
      regulatory T cells will be discussed. Finally, the crucial role of iron
      homeostasis in trypanosomiasis-associated anemia development will be documented
      to stress the analogy with anemia of chronic disease (ACD), hereby providing new
      insight that might contribute to the treatment of ACD.

PMID- 20158498
TI  - Induced, selective proteolysis of MLK3 negatively regulates MLK3/JNK signalling.
AB  - MLK3 (mixed lineage kinase 3) is a MAP3K [MAPK (mitogen-activated protein kinase)
      kinase kinase] that activates multiple MAPK pathways, including the JNK (c-Jun N
      terminal kinase) pathway. Immunoblotting of lysates from cells ectopically
      expressing active MLK3 revealed an additional immunoreactive band corresponding
      to a CTF (C-terminal fragment) of MLK3. In the present paper we provide evidence
      that MLK3 undergoes proteolysis to generate a stable CTF in response to different
      stimuli, including PMA and TNFalpha (tumour necrosis factor alpha). The cleavage
      site was deduced by Edman sequencing as between Gln251 and Pro252, which is
      within the kinase domain of MLK3. Based on our homology model of the kinase
      domain of MLK3, the region containing the cleavage site is predicted to reside on
      a flexible solvent-accessible loop. Site-directed mutagenesis studies revealed
      that Leu250 and Gln251 are required for recognition by the 'MLK3 protease',
      reminiscent of the substrate specificity of the coronavirus 3C and 3CL proteases.
      Whereas numerous mammalian protease inhibitors have no effect on MLK3
      proteolysis, blockade of the proteasome through epoxomicin or MG132 abolishes PMA
      induced production of the CTF of MLK3. This CTF is able to heterodimerize with
      full-length MLK3, and interact with the active form of the small GTPase Cdc42,
      resulting in diminished activation loop phosphorylation of MLK3 and reduced
      signalling to JNK. Thus this novel proteolytic processing of MLK3 may negatively
      control MLK3 signalling to JNK.

PMID- 20158499
TI  - Multimodality tumor imaging targeting integrin alphavbeta3.
AB  - The cell adhesion molecule integrin alphavbeta3 is an important player in the
      process of tumor angiogenesis and metastasis. Antibodies, peptides,
      peptidomimetics, and small molecule antagonists against integrin alphavbeta3 have
      been shown to induce endothelial apoptosis, to inhibit tumor angiogenesis, and to
      increase endothelial permeability. The ability to quantitatively image integrin
      alphavbeta3 expression in vivo in a noninvasive manner may shed new light into
      the mechanism of angiogenesis and antiangiogenic treatment efficacy based on
      integrin antagonism. Tumor integrin expression imaging will also aid in lesion
      detection, patient stratification, new anti-integrin drug development/validation,
      as well as treatment monitoring and optimization. This review summarizes the
      recent advances in multimodality imaging of tumor integrin alphavbeta3 expression
      using magnetic resonance imaging (MRI), ultrasound, near-infrared (NIR)
      fluorescence, single photon emission computed tomography (SPECT), and positron
      emission tomography (PET).

PMID- 20158500
TI  - Confocal microscopy: comparisons, applications, and problems.

PMID- 20158501
TI  - Perspectives on molecular and anatomical imaging in drug discovery.

PMID- 20158502
TI  - Distinguished photons: increased contrast with multispectral in vivo fluorescence
      imaging.
AB  - Noninvasive in vivo imaging is a rapidly growing field with applications in basic
      biology, drug discovery and clinical medicine. Because of the high cost of
      magnetic resonance (MR)- and computed tomography (CT)-based systems, a great deal
      of effort has gone into developing optical imaging methods, which offer, in some
      modalities, the promise of high spatial resolution and the ability to detect
      multiple markers simultaneously However, the ability to image and quantitate
      fluorescently labeled tumors and other fluorescently labeled markers in vivo has
      generally been limited by the autofluorescence of the tissue, which reduces the
      sensitivity of detection and accuracy of quantitation of the labeled target.
      Multispectral imaging methodology, which spectrally characterizes and
      computationally eliminates autofluorescence, enhances signal-to-background
      dramatically, revealing otherwise invisible labeled targets. Signal-to-noise
      considerations can guide the choice of appropriate sensors for fluorescence-based
      imaging, which generally does not benefit from the use of highly cooled (and
      expensive) cameras. Effective use of spectral tools to remove autofluorescence
      signal requires accurate spectra of the individual components. Using manual and
      automated algorithms to generate these spectra, it is possible to detect as many
      as three fluorescent protein-labeled tumors and two separate autofluorescent
      signals in a single subject.

PMID- 20158503
TI  - Spectral domain optical coherence tomography: a better OCT imaging strategy.
AB  - This paper reviews the current state of research in spectral domain optical
      coherence tomography (SDOCT). SDOCT is an interferometric technique that provides
      depth-resolved tissue structure information encoded in the magnitude and delay of
      the back-scattered light by spectral analysis of the interference fringe pattern.
      There are two approaches to SDOCT--one that uses a broadband source and a
      spectrometer to measure the interference pattern as a function of wavelength and
      the other that utilizes a narrowband tunable laser that is swept linearly in k
      approximately 1/lambda space during spectral fringe data acquisition. Unlike time
      domain (TD) OCT, the reference arm is stationary in both SDOCT methods, which
      allows for ultra high-speed OCT imaging. Owing to its high speed and superior
      sensitivity, SDOCT has become indispensable in biomedical imaging applications.
      After a brief introduction and a discussion on sensitivity advantage, methods of
      implementation of the two SDOCT schemes will be presented. The two peer
      approaches are compared in speed, scan depth range, complexity, spectral regions
      of operation, and methods of detection. The review also discusses OCT
      enhancements and functional methods based on SDOCT format and concludes with
      possible directions that this research may take in the near future.

PMID- 20158504
TI  - Classifying syncope: the need for less confusion.

PMID- 20158505
TI  - Differential age-related changes in motor unit properties between elbow flexors
      and extensors.
AB  - AIM: Healthy adult ageing of the human neuromuscular system is comprised of
      changes that include atrophy, weakness and slowed movements with reduced spinal
      motor neurone output expressed by lower motor unit discharge rates (MUDRs). The
      latter observation has been obtained mostly from hand and lower limb muscles. The
      purpose was to determine the extent to which elbow flexor and extensor
      contractile properties, and MUDRs in six old (83 +/- 4 years) and six young (24
      +/- 1 years) men were affected by age, and whether any adaptations were similar
      for both muscle groups. METHODS: Maximal isometric voluntary contraction (MVC),
      voluntary activation, twitch contractile properties, force-frequency relationship
      and MUDRs from sub-maximal to maximal intensities were assessed in the elbow
      flexors and extensors. RESULTS: Both flexor and extensor MVCs were significantly
      (P < 0.05) less (approximately 42% and approximately 46% respectively) in the old
      than in the young. Contractile speeds and the force-frequency relationship did
      not show any age-related differences (P > 0.05). For the elbow flexors
      contraction duration was approximately 139 ms and for the extensors it was
      approximately 127 ms for both age groups (P > 0.05). The mean MUDRs from 25% MVC
      to maximum were lower (approximately 10% to approximately 36%) in the old than in
      the young (P < 0.01). These age-related differences were larger for biceps
      (Cohen's d = 8.25) than triceps (Cohen's d = 4.79) brachii. CONCLUSION: Thus, at
      least for proximal upper limb muscles, mean maximal MUDR reductions with healthy
      adult ageing are muscle specific and not strongly related to contractile speed.

PMID- 20158506
TI  - Identification of conditionally essential genes for growth of Pseudomonas putida
      KT2440 on minimal medium through the screening of a genome-wide mutant library.
AB  - In silico models for Pseudomonas putida KT2440 metabolism predict 68 genes to be
      essential for growth on minimal medium. In this study a genome-wide collection of
      single-gene P. putida KT2440 knockouts was generated by mini-Tn5 transposon
      mutagenesis and used to identify genes essential for growth in minimal medium
      with glucose. Our screening of the knockout library allowed us to rescue mutants
      for 48 different knockouts that were conditionally essential for growth on
      minimal medium. The in vivo screening showed that 24 of these mutants had a
      insertion in genes proposed to be conditionally essential based on in silico
      models, whereas another 24 newly implicated conditionally essential genes have
      been found. For 10 of the in silico proposed conditionally essential genes not
      found in the screening, knockout mutants were available at the Pseudomonas
      Reference Culture Collection. These mutants were tested for conditional growth on
      minimal medium, but none of them was shown to be essential, suggesting that the
      in silico proposal was inaccurate. Among the set of identified conditionally
      essential genes were a number of genes involved in the biosynthesis of certain
      amino acids and vitamins. Auxotrophs for all amino acids predicted by the in
      silico models were found and, in addition, we also found auxotrophs for proline,
      serine, threonine and methionine, as well as auxotrophs for biotin, nicotinate
      and vitamin B12 that were not predicted in silico. Metabolic tests were performed
      to validate the mutants' phenotypes. Auxotrophies for l-Arg, l-Leu, l-Pro and l
      Cys were bypassed by external addition of the corresponding d-amino acids,
      suggesting the existence of number of d- to l-amino acid racemases encoded by the
      KT2440 genome. Therefore, the in vivo high-throughput analysis presented here
      provides relevant insights into the metabolic cross-road of biosynthetic pathways
      in this microorganism, as well as valuable information for the fine tuning of
      current in silico metabolic models.

PMID- 20158507
TI  - Phylogenetic diversity and metagenomics of candidate division OP3.
AB  - Except for environmental 16S rRNA gene sequences, no information is available for
      members of the candidate division OP3. These bacteria appear to thrive in anoxic
      environments, such as marine sediments, hypersaline deep sea, freshwater lakes,
      aquifers, flooded paddy soils and methanogenic bioreactors. The 16S rRNA
      phylogeny suggests that OP3 belongs to the
      Planctomycetes/Verrucomicrobia/Chlamydiae (PVC) superphylum. Metagenomic fosmid
      libraries were constructed from flooded paddy soil and screened for 16S rRNA gene
      containing fragments affiliated with the PVC superphylum. The screening of 63 000
      clones resulted in 23 assay-positive fosmids, of which three clones were
      affiliated with OP3. The 16S rRNA gene sequence divergence between the fragments
      OP3/1, OP3/2 and OP3/3 ranges from 18% to 25%, indicating that they belong to
      different OP3 subdivisions. The 23S rRNA phylogeny confirmed the membership of
      OP3 in the PVC superphylum. Sequencing the OP3 fragments resulted in a total of
      105 kb of genomic information and 90 ORFs, of which 47 could be assigned a
      putative function and 11 were conserved hypothetical. Using BLASTP searches, a
      high proportion of ORFs had best matches to homologues from Deltaproteobacteria,
      rather than to those of members of the PVC superphylum. On the fragment OP3/3, a
      cluster of nine ORFs was predicted to encode the bacterial NADH dehydrogenase I.
      Given the high proportion of homologues present in deltaproteobacteria and anoxic
      conditions in the natural environment of OP3 bacteria, the detection of NADH
      dehydrogenase I may suggest an anaerobic respiration mode. Oligonucleotide
      frequencies calculated for OP3/1, OP3/2 and OP/3 show high intraphylum
      correlations. This novel sequence information could therefore be used to identify
      OP3-related fragments in large metagenomic data sets using marker gene
      independent procedures in the future. In addition to the OP3 fragments, a single
      metagenomic fragment affiliated with the candidate division BRC1 was obtained and
      analysed.

PMID- 20158508
TI  - Clinical features of non-hypertensive lobar intracerebral hemorrhage related to
      cerebral amyloid angiopathy.
AB  - BACKGROUND AND PURPOSE: The present study aims to clarify the clinical features
      of non-hypertensive cerebral amyloid angiopathy-related lobar intracerebral
      hemorrhage (CAA-L-ICH). METHODS: We investigated clinical, laboratory, and
      neuroimaging findings in 41 patients (30, women; 11, men) with pathologically
      supported CAA-L-ICH from 303 non-hypertensive Japanese patients aged >OR=55,
      identified via a nationwide survey as symptomatic CAA-L-ICH. RESULTS: The mean
      age of patients at onset of CAA-L-ICH was 73.2 +/- 7.4 years; the number of
      patients increased with age. The corrected female-to-male ratio for the
      population was 2.2, with significant female predominance. At onset, 7.3% of
      patients received anti-platelet therapy. In brain imaging studies, the actual
      frequency of CAA-L-ICHs was higher in the frontal and parietal lobes; however,
      after correcting for the estimated cortical volume, the parietal lobe was found
      to be the most frequently affected. CAA-L-ICH recurred in 31.7% of patients
      during the average 35.3-month follow-up period. The mean interval between
      intracerebral hemorrhages (ICHs) was 11.3 months. The case fatality rate was
      12.2% at 1 month and 19.5% at 12 months after initial ICH. In 97.1% of patients,
      neurosurgical procedures were performed without uncontrollable intraoperative or
      post-operative hemorrhage. CONCLUSIONS: Our study revealed the clinical features
      of non-hypertensive CAA-L-ICH, including its parietal predilection, which will
      require further study with a larger number of patients with different ethnic
      backgrounds.

PMID- 20158509
TI  - Triglyceride level modifying functional variants of GALTN2 and MLXIPL in patients
      with ischaemic stroke.
AB  - BACKGROUND: Recent genome-wide studies identified several genetic variants
      associated with blood lipid level alterations. Because affected lipid metabolism
      can confer risk to the development of ischaemic stroke, we studied three
      polymorphisms reportedly associated with triglyceride-level changes, rs17145738
      and rs3812316 of the MLXIPL locus, and rs4846914 variant of GALNT2 gene in
      biobanked samples of patients with stroke. This pool of samples was previously
      investigated for haplotype tagging minor alleles of apolipoprotein A5 gene (T
      1131C, T1259C, IVS3+G476A and C56G), and an association was found between the
      minor allele carriage and the triglyceride levels, and also these variants were
      found to confer risk to the development of stroke. METHODS: Here, a total of 467
      patients with stroke, stratified as large vessel, small vessel and mixed stroke
      groups, and 156 control subjects were genotyped using PCR-RFLP methods. RESULTS:
      In the current study, we could not verify association of the variants analyzed
      either with triglyceride and total cholesterol levels or with the risk of
      ischaemic stroke susceptibility. CONCLUSIONS: The data presented here revealed
      differentiated risk nature of the triglyceride level modifying natural gene
      variants.

PMID- 20158510
TI  - Left temporal low-frequency rTMS for the treatment of tinnitus: clinical
      predictors of treatment outcome--a retrospective study.
AB  - BACKGROUND: There is increasing evidence that repetitive transcranial magnetic
      stimulation (rTMS) can reduce chronic tinnitus. However, treatment results are
      characterized by high interindividual variability. Therefore, the identification
      of predictors for treatment response is of high clinical relevance. METHODS:
      Clinical data of 194 patients with tinnitus were evaluated. All patients were
      treated with a standardized rTMS procedure (1 Hz, 10 days, 2000 stimuli/day, over
      the left temporal cortex). A potential influence on the outcome was analysed for
      the following parameters: age, gender, depression scores in Beck Depression
      Inventory (BDI) and tinnitus severity (TQ) before rTMS, lateralization, frequency
      and duration of tinnitus and extent of hearing loss. RESULTS: An effect of
      tinnitus laterality was observed. In patients with left-sided or bilateral
      tinnitus, rTMS resulted in a statistically significant reduction of TQ scores,
      whereas patients with right-sided tinnitus did not show a significant improvement
      after rTMS treatment. However, in correlation analyses, we found a trend which
      did not reach statistical significance that in the subgroup of treatment
      responders tinnitus duration influenced rTMS outcome. In addition, a multiple
      regression analysis identified the TQ score at baseline as a significant
      predictor for treatment outcome. For all other investigated parameters, no
      statistically significant effects were found. CONCLUSIONS: This study suggests
      that left temporal low-frequency rTMS has beneficial effects in left-sided and
      bilateral tinnitus, but not in right-sided tinnitus. In line with the results
      from earlier studies involving smaller samples, tinnitus duration was found to
      influence rTMS outcome.

PMID- 20158511
TI  - A novel PSEN1 mutation (K239N) associated with Alzheimer's disease with wide
      range age of onset and slow progression.
AB  - OBJECTIVE: To describe a novel mutation (K239N) in the PSEN1 associated with
      familial Alzheimer's disease (AD). METHODS AND RESULTS: The proband was a man who
      developed cognitive decline with marked behavioural abnormalities at age 57. At
      age 70, he was admitted into a psychiatric facility because of aggressiveness and
      a suicide attempt. Family history was consistent with autosomal dominant AD. One
      of the two other family members studied presented also with prominent behavioural
      symptoms at age 42 and has also been forced into a psychiatric facility because
      of aggressiveness at age 56. The remainder patient has presented a prototypical
      AD, but starting at age 71. Direct sequencing of PSEN1 in the three living
      affected members disclosed a heterozygous G to C transition in exon 7 of PSEN1
      leading to the K239N mutation. CONCLUSION: The K239N mutation is associated with
      autosomal dominant AD with a wide range of age of onset and incomplete penetrance
      at the age of 65, prominent behavioural features and slow progression.

PMID- 20158512
TI  - Paroxysmal kinesigenic choreoathetosis: evidence of linkage to the
      pericentromeric region of chromosome 16 in four Chinese families.
AB  - BACKGROUND: Paroxysmal kinesigenic choreoathetosis (PKC) is an autosomal dominant
      condition characterized by abnormal involuntary movements precipitated by sudden
      movement. The pericentromeric region of chromosome 16 has been linked to PKC by
      several reports. This study was to localize and identify PKC gene in four Chinese
      PKC families. METHODS: Genetic linkage mapping with eight markers spanning
      chromosome 16p12-q13 was performed in 43 family members. Genome-wide single
      nucleotide polymorphism (SNP) scans were performed on four individuals in Family
      1 in which infantile convulsion (IC) was co-inherited with PKC. RESULTS:
      Individuals in Family 1 presented with both IC and paroxysmal choreoathetosis
      (ICCA), and Families 2, 3, and 4 presented only with PKC. Evidence for linkage
      was found with a maximum two-point LOD score of 4.89 for D16S690 (theta = 0.0)
      and a maximum multipoint LOD score was 5.34 between D16S3080 and D16S3136.
      Haplotype analysis showed the disease locus was between D16S3093 and D16S3057. A
      total of 84 SNPs spanned on 16q12.1-q13 was not segregated with the PKC
      phenotype, which defined an unlinked region from rs9933187 to rs8044753. Thus,
      the critical region of the PKC gene is across the pericentromeric region of
      chromosome 16, and most likely maps to a region of 20.5 Mb (6.2 cM) between
      D16S3093 and rs9933187 (16p11.2-q12.1). CONCLUSION: The assignment of the locus
      for PKC to the pericentromeric region of chromosome 16 is confirmed and
      putatively narrowed in the present study.

PMID- 20158513
TI  - Changes in nutritional status and body composition during enzyme replacement
      therapy in adult-onset type II glycogenosis.
AB  - BACKGROUND: In adult glycogen storage disease type II (GSDII), a single-gene
      mutation causes reduction of the lysosomal enzyme acid alpha-glucosidse. This
      produces a chronic proximal myopathy with respiratory involvement. Enzyme
      replacement treatment (ERT) has recently become available and is expected to
      improve muscle strength. This should result in increased lean body mass. In this
      study we evaluate body composition and nutritional status in GSDII, and assess
      whether these parameters changed during treatment. METHODS: Seventeen patients
      with late-onset GSDII, aged 52.6 +/- 16.8 years, received ERT for >18 months.
      Dietary habits and metabolic profiles of glucids, lipids, and proteins were
      assessed. Body composition was calculated using anthropometry and bioelectrical
      impedence analysis. RESULTS: On inclusion, we found increased fat mass (FM) in
      five patients in severe disease stage; all had normal body mass index (BMI). FM
      correlated inversely, and lean mass (LM) directly, with creatine kinase,
      prealbumin and albumin levels. After treatment, BMI and FM significantly
      increased, while LM only showed a trend toward increase. Prealbumin and albumin
      levels increased as early as after the first months of ERT. DISCUSSION: Body mass
      index value may underestimate FM in patients in severe stage of disease, due to
      altered body composition. In severely affected patients, laboratory parameters
      revealed a relative protein malnutrition, that was reversed by ERT, this
      reflecting restoration of normal muscle metabolic pathways. Increased BMI may
      indicate a reduction in energy consumption during exercise or respiration, along
      with clinical improvement.

PMID- 20158514
TI  - Electrophysiological sensory demyelination in typical chronic inflammatory
      demyelinating polyneuropathy.
AB  - BACKGROUND: The presence of electrophysiological demyelination of sensory nerves
      is not routinely assessed in the evaluation of suspected chronic inflammatory
      demyelinating polyneuropathy (CIDP). Whether this can be useful is unknown.
      METHODS: We compared, using surface recording techniques, in 19 patients with
      typical CIDP and 26 controls with distal large fibre sensory axonal neuropathy,
      the forearm median sensory conductions, sensory nerve action potential (SNAP)
      amplitudes and durations and sensory nerve conduction velocities (SNCVs) of
      median, radial and sural nerves. RESULTS: Median nerve sensory conduction block
      (SCB) across the forearm was greater in CIDP patients than in controls (P =
      0.005). SNAP durations were longer in CIDP patients for median (P = 0.001) and
      sural nerves (P = 0.004). Receiver operating characteristic (ROC) curves provided
      sensitive (>40%) and specific (>95%) cut-offs for median nerve SCB as well as
      median and sural SNAP durations. SNCVs were significantly slower for median and
      sural nerves in CIDP patients, but ROC curves did not demonstrate cut-offs with
      useful sensitivities/specificities. Median SCB or prolonged median SNAP duration
      or prolonged sural SNAP duration offered a sensitivity of 73.7% for CIDP and
      specificity of 96.2%. Used as additional parameters, they improved diagnostic
      sensitivity of the American Academy of Neurology (AAN) criteria for CIDP of 1991,
      from 42.1% to 78.9% in this population, with preserved specificity of 100%.
      DISCUSSION: Sensory electrophysiological demyelination is present and may be
      diagnostically useful in typical CIDP. SCB detection and SNAP duration
      prolongation appear to represent more useful markers of demyelination than SNCV
      reduction.

PMID- 20158515
TI  - Prevalence of depression in amyotrophic lateral sclerosis and other motor
      disorders.
AB  - BACKGROUND: Research suggests the prevalence of severe depression in ALS is <20%.
      In contrast, studies have reported that severe depression affects 40-50% of
      patients with other neurodegenerative motor conditions (e.g. multiple sclerosis,
      Parkinson's disease and Huntington's disease). The comparison with such disorders
      has generated a clinical impression that patients with ALS have surprisingly low
      rates of depression. However, comparisons with such disorders do not take into
      account the markedly different pathological, physical and behavioural profiles
      associated with these disorders. To assess further the extent to which ALS is
      associated with a low prevalence of depression, we compared the prevalence of
      depression in patients with ALS to that in patients with neuromuscular disorders
      with more comparable disease profiles. METHODS: The Beck Depression Inventory-II
      (BDI-II), the Major Depression Inventory (MDI), the Hospital Anxiety and
      Depression Scale (HADS) and the ALS Functional Rating Scale-Revised were sent to
      212 patients from a tertiary referral Motor Nerve Clinic in London, UK. RESULTS:
      Data were obtained from 51 people with ALS and 39 with other neuromuscular
      disorders. The non-ALS group included patients diagnosed with disorders that are
      characterized by motor neurone dysfunction and/or a decline in everyday function.
      Analyses revealed no between-group differences on severity and prevalence rates
      of depression according to the BDI-II, HADS Depression Subscale and MDI.
      CONCLUSIONS: Our findings do not support the impression that patients with ALS
      have lower rates of depression than patients with other varied neuromuscular
      disorders.

PMID- 20158516
TI  - High-resolution ultrasound in the evaluation and prognosis of Bell's palsy.
AB  - INTRODUCTION: Bell's palsy is a commonly encountered paralysis of the facial
      nerve occurring worldwide. Prognosis for Bell's palsy is good, but the proportion
      of patients with poor outcomes may reach 30%. Ultrasound (US) may provide a novel
      approach for evaluating and prognosticating Bell's palsy, in comparison with
      known electrophysiological techniques. METHODS: In this study, we measured the
      diameter of the distal facial (VII) nerve using US in patients with Bell's palsy
      treated with prednisolone, in comparison with healthy controls. Blink reflex and
      VII nerve conduction studies were also performed. Studies were prospective and
      performed within 1 week of disease onset. RESULTS: Our results have shown that
      diameter of the distal VII nerve is a good predictor of favorable (positive
      predictive value: 100%) and bad outcomes (negative predictive value: 77%) in
      Bell's palsy at 3 months after clinical presentation. Furthermore, we also noted
      the lack of correlation of VII diameter with conventional VII nerve conduction
      studies (NCS) and blink reflex studies. US was superior to VII nerve conduction
      and blink reflex studies in outcome prediction. CONCLUSIONS: This first study
      utilizing US in Bell's palsy highlights its role in outcome prediction and
      contributes to our understanding of recovery processes in this common
      neurological disorder.

PMID- 20158517
TI  - Risk factors for periodic breathing in acute stroke: tracheobronchial infection.
AB  - BACKGROUND AND PURPOSE: Despite evidence from clinical and population studies,
      the aim of the present study was to suggest that multiple factors contribute to
      periodic breathing (PB). However, little information has been focused on episodes
      of tracheobronchial infections (TBI) preceding PB onset. METHODS: Thirty subjects
      with acute stroke who had PB and 41 subjects with acute stroke that of a sex- and
      age-matched control group without PB were retrospectively evaluated. Stroke
      location, extent of stroke (demonstrated on CT or MRI), and characteristics of
      TBI before PB were assessed. PB diagnosis was carried out using a portable device
      and a pulse oximeter. Risk factors for patients with PB were compared with those
      without PB by univariate and multivariate analysis. RESULTS: Twenty-four TBI in
      30 patients with PB and 11 TBI in 41 patients with non-PB were diagnosed. There
      was no significant difference in age, sex, body mass index, stroke type, stroke
      location, or underlying diseases between the two groups (P > 0.05). There was a
      significant difference in snoring, first recurrent stroke, Glasgow Coma Scale,
      congestive heart failure, TBI, and inflammatory responses between the PB and non
      PB group (P < 0.05). Multiple logistic regression analyses showed a difference in
      the prevalence of snoring (OR = 10.813, CI = 2.131-54.866, P < 0.01), TBI (OR =
      5.313, CI = 1.241-22.740, P < 0.05), and inflammatory responses (OR = 7.315, CI =
      1.253-43.123, P < 0.05) between the two groups. CONCLUSIONS: In addition to
      snoring, TBI and inflammatory responses are the two independent predictors for PB
      in patients with acute stroke. Clinicians should be encouraged to systematically
      evaluate TBI and inflammatory responses before PB in patients with acute stroke.

PMID- 20158518
TI  - 'Fish matters': the relevance of fish skin biology to investigative dermatology.
AB  - Fish skin is a multi-purpose tissue that serves numerous vital functions
      including chemical and physical protection, sensory activity, behavioural
      purposes or hormone metabolism. Further, it is an important first-line defense
      system against pathogens, as fish are continuously exposed to multiple microbial
      challenges in their aquatic habitat. Fish skin excels in highly developed
      antimicrobial features, many of which have been preserved throughout evolution,
      and infection defense principles employed by piscine skin are still operative in
      human skin. This review argues that it is both rewarding and important for
      investigative dermatologists to revive their interest in fish skin biology, as it
      provides insights into numerous fundamental issues that are of major relevance to
      mammalian skin. The basic molecular insights provided by zebrafish in vivo
      genomics for genetic, regeneration and melanoma research, the complex
      antimicrobial defense systems of fish skin and the molecular controls of
      melanocyte stem cells are just some of the fascinating examples that illustrate
      the multiple potential uses of fish skin models in investigative dermatology. We
      synthesize the essentials of fish skin biology and highlight selected aspects
      that are of particular comparative interest to basic and clinically applied human
      skin research.

PMID- 20158519
TI  - Catalytically active membrane-distal phosphatase domain of receptor protein
      tyrosine phosphatase alpha is required for Src activation.
AB  - Receptor protein-tyrosine phosphatase alpha (RPTPalpha) is a transmembrane
      protein with tandem cytoplasmic phosphatase domains. Most of the catalytic
      activity is contained by the membrane-proximal catalytic domain (D1). We found a
      spontaneous Arg554 to His mutation in the pTyr recognition loop of the membrane
      distal phosphatase domain (D2) of a human patient. This mutation was not linked
      to the disease. Here, we report that the R554H mutation abolished RPTPalpha-D2
      catalytic activity. The R554H mutation impaired Src binding to RPTPalpha.
      RPTPalpha, with a catalytic site cysteine to serine mutation in D2, also
      displayed diminished binding to Src. Concomitant with decreased Src binding of
      the R554H and C723S mutants compared with wild-type RPTPalpha, enhanced
      phosphorylation of the inhibitory Src Tyr527 site was observed, as well as
      reduced Src activation. To confirm that catalytic activity of RPTPalpha-D2 was
      required for these effects, we analyzed a third mutant, RPTPalpha-R729K, which
      had an inactive D2. Again, Src binding was reduced and Tyr527 phosphorylation was
      enhanced. Our results suggest that a catalytically active D2 is required for
      RPTPalpha to bind and dephosphorylate its well-characterized substrate, Src.

PMID- 20158520
TI  - Nigrocin-2 peptides from Chinese Odorrana frogs--integration of UPLC/MS/MS with
      molecular cloning in amphibian skin peptidome analysis.
AB  - Peptidomics is a powerful set of tools for the identification, structural
      elucidation and discovery of novel regulatory peptides and for monitoring the
      degradation pathways of structurally and catalytically important proteins.
      Amphibian skin secretions, arising from specialized granular glands, often
      contain complex peptidomes containing many components of entirely novel structure
      and unique site-substituted analogues of known peptide families. Following the
      discovery that the granular gland transcriptome is present in such secretions in
      a PCR-amenable form, we designed a strategy for peptide structural
      characterization involving the integration of 'shotgun' cloning of cDNAs encoding
      peptide precursors, deduction of putative bioactive peptide structures, and
      confirmation of these structures using tandem MS/MS sequencing. Here, we
      illustrate this strategy by means of elucidation of the primary structures of
      nigrocin-2 homologues from the defensive skin secretions of four species of
      Chinese Odorrana frogs, O. schmackeri, O. livida, O. hejiangensis and O.
      versabilis. Synthetic replicates of the peptides were found to possess
      antimicrobial activity. Nigrocin-2 peptides occur widely in the skin secretions
      of Asian ranid frogs and in those of the Odorrana group, and are particularly
      well-represented and of diverse structure in some species. Integration of the
      molecular analytical technologies described provides a means for rapid structural
      characterization of novel peptides from complex natural libraries in the absence
      of systematic online database information.

PMID- 20158521
TI  - Daunorubicin efflux in Streptomyces peucetius modulates biosynthesis by feedback
      regulation.
AB  - Streptomyces peucetius self-resistance genes drrA and drrB encode membrane
      associated proteins that function like an ABC transporter for the efflux of
      daunorubicin and to maintain a constant subinhibitory physiological concentration
      of the drug within the cell. In this study, the drrA and drrB operons were
      disrupted for investigating drug production, self-resistance and regulation. The
      drrA-drrB null mutant was highly sensitive to daunorubicin. A 10-fold decrease in
      drug production was observed in the null mutant compared with the wild-type
      strain. We propose that the absence of a drug-specific efflux pump increases the
      intracellular concentration of daunorubicin, which is sensed by the organism to
      turn down drug production. Quantitative real-time PCR analysis of the mutant
      showed a drastic reduction in the expression of the key regulator dnrI and
      polyketide synthase gene dpsA. However, the expression of regulatory genes dnrO
      and dnrN was increased. Feedback regulation based on the intracellular
      daunorubicin concentration is discussed.

PMID- 20158522
TI  - Gene targeting for O-methyltransferase genes, mycE and mycF, on the chromosome of
      Micromonospora griseorubida producing mycinamicin with a disruption cassette
      containing the bacteriophage phi C31 attB attachment site.
AB  - Mycinamicin, a 16-membered macrolide antibiotic produced by Micromonospora
      griseorubida, comprises a macrolactone and two deoxysugars: desosamine and
      mycinose. Mycinose is synthesized through two modification steps: the methylation
      of 6-deoxyallose in mycinamicin VI and of javose in mycinamicin III. To confirm
      the role of mycE and mycF genes in mycinamicin biosynthesis in M. griseorubida,
      disruption mutants of mycE and mycF were constructed by disruption plasmids
      containing attB in the disruption cassette FRT-neo-oriT-FRT-attB for the
      integration of phiC31-derivative vector plasmids; the disruption mutants were
      complemented through the integration of pSET152 derivatives containing intact
      mycE or mycF into the artificially inserted attB site. These disruption mutants
      did not produce mycinamicin II, but mainly accumulated mycinamicins VI and III,
      indicating that MycE and MycF methylated the C2''-OH group of 6-deoxyallose in
      mycinamicin VI and the C3''-OH group of C2''-methylated 6-deoxyallose in
      mycinamicin III, respectively. The complemented strains of mycE and mycF
      recovered the mycinamicin II productivity.

PMID- 20158523
TI  - Absence of the aflatoxin biosynthesis gene, norA, allows accumulation of
      deoxyaflatoxin B1 in Aspergillus flavus cultures.
AB  - Biosynthesis of the highly toxic and carcinogenic aflatoxins in select
      Aspergillus species from the common intermediate O-methylsterigmatocystin has
      been postulated to require only the cytochrome P450 monooxygenase, OrdA (AflQ).
      We now provide evidence that the aryl alcohol dehydrogenase NorA (AflE) encoded
      by the aflatoxin biosynthetic gene cluster in Aspergillus flavus affects the
      accumulation of aflatoxins in the final steps of aflatoxin biosynthesis. Mutants
      with inactive norA produced reduced quantities of aflatoxin B(1) (AFB(1)), but
      elevated quantities of a new metabolite, deoxyAFB(1). To explain this result, we
      suggest that, in the absence of NorA, the AFB(1) reduction product, aflatoxicol,
      is produced and is readily dehydrated to deoxyAFB(1) in the acidic medium,
      enabling us to observe this otherwise minor toxin produced in wild-type A.
      flavus.

PMID- 20158524
TI  - rpoA is a useful gene for identification and classification of Streptococcus
      pneumoniae from the closely related viridans group streptococci.
AB  - Streptococcus pneumoniae, the leading etiological agent of pneumonia, shares a
      high degree of DNA sequence homology with the viridans group of streptococci. The
      clinical and pathological manifestations may present with different features, and
      discrimination between S. pneumoniae and its close viridans cocci relatives, such
      as Streptococcus mitis and Streptococcus oralis, is still quite difficult. The
      445-bp sequences of the N-terminal region of rpoA from nine S. pneumoniae, seven
      S. mitis, ten S. oralis, and two related strains were determined and compared
      with their respective 16S rRNA gene sequences to establish their usefulness in
      phylogenetic analysis. Pairwise comparisons of rpoA sequences among the species
      showed higher rates of evolution with lower similarities (92.3-100%) than those
      of 16S rRNA genes (96.8-100%). The rpoA-based phylogeny generated deeper branches
      and presented improved discriminatory resolution than the 16S rRNA gene-based
      phylogeny. These results show that rpoA sequences represent a consistent, but
      more discriminating, genomic marker than 16S rRNA gene sequences for
      investigating the evolutionary relationships of Streptococcus at the species
      level. rpoA could be a useful marker for identifying and classifying S.
      pneumoniae, S. mitis, and S. oralis from closely related taxa.

PMID- 20158525
TI  - Genetic diversity and diet specificity of ruminal Prevotella revealed by 16S rRNA
      gene-based analysis.
AB  - 16S rRNA gene-based analysis of rumen Prevotella was carried out to estimate the
      diversity and diet specificity of bacteria belonging to this genus. Total DNA was
      extracted from the rumen digesta of three sheep fed two diets with different hay
      to-concentrate ratios (10 : 1 and 1 : 2). Real-time PCR quantification of
      Prevotella revealed that the relative abundance of this genus in the total rumen
      bacteria was up to 19.7%, while the representative species Prevotella bryantii
      and Prevotella ruminicola accounted for only 0.6% and 3.8%, respectively.
      Denaturing gradient gel electrophoresis analysis for Prevotella revealed shifts
      in the community composition with the diet. Analysis of 16S rRNA gene clone
      libraries showed significant differences (P=0.001) between clones detected from
      the sheep on the diets with different hay-to-concentrate ratios. The majority
      (87.8%) of Prevotella clones had <97% sequence similarity with known rumen
      Prevotella. These data suggest that uncultured Prevotella is more abundant than
      known Prevotella and that members of this genus appear to have specific metabolic
      niches.

PMID- 20158526
TI  - Recombinant activated factor VII safety and efficacy in the treatment of cranial
      haemorrhage in patients with congenital haemophilia with inhibitors: an analysis
      of the Hemophilia and Thrombosis Research Society Registry (2004-2008).
AB  - Cranial haemorrhage (CH) is a potentially serious complication in patients with
      severe congenital haemophilia with inhibitors (CHwI). Treatment includes
      bypassing agents, such as recombinant activated factor VII (rFVIIa). To examine
      the US experience in treating CH with rFVIIa, a retrospective review of the
      Hemophilia and Thrombosis Research Society 2004-2008 database was conducted.
      Among 29 patients with CHwI, 56 of the reported haemorrhages met the study
      criteria. Of these, 75% were traumatic and 80% were extracranial (ECH). The
      majority (8/11, 73%) of intracranial haemorrhages (ICHs) developed spontaneously.
      Conversely, most ECHs (39/45, 87%) followed trauma. ICHs were treated with a
      median/mean of 23/58 rFVIIa infusions over a median/mean of 7/9 days while ECHs
      were treated with a median/mean of 1/3 infusions (P = 0.011) over a median/mean
      of 1/1 day. The median/mean initial rFVIIa doses for all CHs were 106/137 microg
      kg(-1), and were similar for ICHs and ECHs. All ECHs were effectively controlled
      with rFVIIa; 44/45 bleeds were controlled within 24 h, one bleed was successfully
      treated perioperatively, and 27 ECHs required only a single dose. Nine out of 11
      ICHs were effectively treated with rFVIIa; six ICHs were controlled within 24 h,
      one within 72 h and in two cases haemostasis was achieved during the
      perioperative period. No serious treatment-associated adverse events were
      reported. One patient died as a result of ICH despite the reported control of
      bleeding. In conclusion, standard dosing of rFVIIa was found to be safe and
      effective in treating CH with an efficacy rate of 100% for ECH and 82% for ICH.

PMID- 20158527
TI  - Risk of high-level viraemia in HIV-infected patients on successful antiretroviral
      treatment for more than 6 months.
AB  - OBJECTIVES: According to the Swiss Federal Commission for HIV/AIDS, HIV-infected
      patients on successful antiretroviral treatment have a negligible risk of
      transmitting HIV sexually. We estimated the risk that patients considered to have
      an undetectable viral load (VL) are actually viraemic. METHODS: A Danish,
      population-based nationwide cohort study of HIV-infected patients with VL <51 HIV
      1 RNA copies/mL for more than 6 months was carried out for the study period 2000
      2008. The observation time was calculated from 6 months after the first VL <51
      copies/mL to the last measurement of VL or the first VL >50 copies/mL. The time
      at risk of transmitting HIV sexually was calculated as 50% of the time from the
      last VL <51 copies/mL to the subsequent VL if it was >1000 copies/mL. The outcome
      was the time at risk of transmitting HIV sexually divided by the observation
      time. RESULTS: We identified 2680 study subjects contributing 9347.7 years of
      observation time and 56.4 years of risk of transmitting HIV (VL>1000 copies/mL).
      In 0.6% [95% confidence interval (CI) 0.5-0.8%] of the overall observation time
      the patients had VL >1000 copies/mL. In the first 6 months this risk was
      substantially higher (7.9%; 95% CI 4.5-11.0%), but thereafter decreased and was
      almost negligible after 5 years (0.03%; 95% CI 0.0-0.2%). The risk was higher in
      injecting drug users, but otherwise did not differ between subgroups of patients.
      CONCLUSION: The risk of viraemia and therefore the risk of transmitting HIV
      sexually are high in the first 12 months of successful antiretroviral treatment,
      but thereafter are low.

PMID- 20158528
TI  - Do allergic families avoid keeping furry pets?
AB  - Studies addressing the relationship between pet keeping and development of asthma
      and allergies may be influenced by pet avoidance in families with a history of
      allergic disease. Following a cohort of 1019 children in Oslo till 10 years of
      age, we studied the association of pet keeping with socio-economic factors and
      allergic disease in the family. A family history of asthma and
      rhinoconjunctivitis was not significantly associated with pet ownership at birth
      or with pet removal by 10 years. Acquiring cats and dogs was less likely if the
      child had allergic rhinoconjunctivitis, whereas no association was seen with
      asthma (in any family member). Single parenthood increased the likelihood of
      acquiring a cat, smoking parents more often had cats or dogs, and having older
      siblings was associated with keeping dogs and other furry pets. Among 319
      families reporting pet avoidance, 70% never had pets, 8% had given up pets, and
      22% avoided a particular type of pet only. Twenty-four per cent of the parents
      failed to retrospectively report pet keeping during the child's first year of
      life. Overall, allergic rhinitis, but not asthma was associated with actual pet
      avoidance, whereas the strongest predictors for keeping pets were found to be
      socio-economic factors. PRACTICAL IMPLICATIONS: Allergic disease in a child most
      often does not lead to the removal of the family's furry pet. Pet avoidance is
      associated with allergic symptoms, but not asthma. Socio-economic factors like
      parental education, single parenthood and smoking affects the families' decisions
      on pet keeping, including the type of pets the families will avoid or acquire.
      The large recall error demonstrated points to the need for prospective data
      regarding pet keeping.

PMID- 20158529
TI  - Tooth survival following non-surgical root canal treatment: a systematic review
      of the literature.
AB  - AIMS: To investigate (i) the effect of study characteristics on reported tooth
      survival after root canal treatment (RCTx) and (ii) the effect of clinical
      factors on the proportion of root filled teeth surviving after RCTx. METHODOLOGY:
      Longitudinal human clinical studies investigating tooth survival after RCTx which
      were published up to the end of 2007 were identified electronically (MEDLINE and
      Cochrane database 1966-2007 December, week 4). In addition, four journals (Dental
      Traumatology, International Endodontic Journal, Journal of Endodontics, Oral
      Surgery Oral Medicine Oral Pathology Oral Radiology & Endodontics),
      bibliographies of all relevant articles and review articles were hand searched.
      Two reviewers (Y-LN, KG) assessed and selected the studies based on specified
      inclusion criteria and extracted the data onto a pre-designed proforma,
      independently. The criteria were as follows: (i) clinical study on RCTx; (ii)
      stratified analysis of primary and secondary RCTx available; (iii) sample size
      given and larger than 10; (iv) at least 6-month postoperative review; (v) success
      based on survival of tooth; and (vi) proportion of teeth surviving after
      treatment given or could be calculated from the raw data. Three strands of
      evidence or analyses were used to triangulate a consensus view. The reported
      findings from individual studies, including those excluded for quantitative
      analysis, were utilized for the intuitive synthesis, which constituted the first
      strand of evidence. Secondly, the pooled weighted proportion of teeth surviving
      and thirdly the combined effects of potential prognostic factors were estimated
      using the fixed and random effects meta-analyses on studies fulfilling all the
      inclusion criteria. RESULTS: Of the 31 articles identified, 14 studies published
      between 1993 and 2007 were included. The majority of studies were retrospective
      (n = 10) and only four prospective. The pooled percentages of reported tooth
      survival over 2-3, 4-5 and 8-10 years following RCTx were 86% (95% CI: 75%, 98%),
      93% (95% CI: 92%, 94%) and 87% (95% CI: 82%, 92%), respectively. Substantial
      differences in study characteristics were found to hinder effective direct
      comparison of findings. Evidence for the effect of prognostic factors on tooth
      survival was weak. Based on the data available for meta-analyses, four conditions
      were found to significantly improve tooth survival. In descending order of
      influence, the conditions increasing observed proportion of survival were as
      follows: (i) a crown restoration after RCTx; (ii) tooth having both mesial and
      distal proximal contacts; (iii) tooth not functioning as an abutment for
      removable or fixed prosthesis; and (iv) tooth type or specifically non-molar
      teeth. Statistical heterogeneity was substantial in some cases but its source
      could not be investigated because of insufficient available information.
      CONCLUSIONS: The pooled proportion of teeth surviving over 2-10 years following
      RCTx ranged between 86% and 93%. Four factors (listed above) were identified as
      significant prognostic factors with concurrence between all three strands of
      evidence.

PMID- 20158530
TI  - The effect of irrigation time, root morphology and dentine thickness on tooth
      surface strain when using 5% sodium hypochlorite and 17% EDTA.
AB  - AIM: To evaluate the effect of irrigation with 5% sodium hypochlorite (NaOCl)
      alone and in conjunction with 17% ethylenediaminetetraacetic acid (EDTA) on tooth
      surface strain (TSS) and to analyse the influence of irrigation time, root
      morphology and dentine thickness. METHODOLOGY: Thirty-six single-rooted pre
      molars with single canals had their crown and enamel reduced and root canals
      prepared using a standardized protocol. Teeth were grouped according to
      anatomical criteria and randomly distributed to experimental irrigation groups:
      (A) saline (negative control); (B) 5% NaOCl (positive control); (C) 5% NaOCl
      alternated with 17% EDTA. TSS was measured using electrical strain gauges bonded
      to the cervico-proximal part of the tooth. Teeth, mounted in clear acrylic resin
      placed in a universal testing machine, were subjected to nine consecutive 10-min
      irrigation periods followed by non-destructive occlusal loading to record TSS.
      Statistical analysis was carried out using two-way hierarchical anova and post
      hoc multiple comparisons. RESULTS: Two groups showed an increase in TSS from the
      baseline (initial 10-min irrigation with saline). Group A showed a negligible
      reduction of 1.2% (343-339 muepsilon), which was not statistically significant (P
      = 0.7). Group B showed a highly significant (P = 0.001) increase in TSS by 53.7%
      (178-253 muepsilon), and group C showed a significant (P = 0.02) increase in TSS
      by 17.4% (163-192 muepsilon). The rate of change in TSS was significantly
      different between test groups. The length of the tooth (P = 0.04) as well as the
      mesio-distal (P = 0.05) width had significant effects on TSS. CONCLUSIONS:
      Irrigation with 5% with or without 17% EDTA increased TSS. The increase was
      significantly greater with 5% NaOCl alone than with 5% NaOCl alternated with 17%
      EDTA in contrast to previous findings with longer duration of irrigant exposure.
      Tooth length and mesio-distal root width significantly contributed to the
      increase in TSS.

PMID- 20158531
TI  - Micro-CT evaluation of residual material in canals filled with Activ GP or
      GuttaFlow following removal with NiTi instruments.
AB  - AIM: To assess the efficacy of removing Activ GP or GuttaFlow from canals using
      NiTi instruments. METHODOLOGY: Root canals in 55 extracted pre-molars were
      prepared to apical size 40, 0.04 taper. The teeth were imaged with micro-CT, and
      30 teeth selected that had consistent apical size and taper of the shaped canals.
      They were randomly assigned to root filling with either the glass-ionomer-based
      ActivGP system (n = 15) or the polyvinylsiloxane-based GuttaFlow system (n = 15).
      After 2 weeks, canals were retreated stepwise with size 40-50 EndoSequence 0.04
      taper instruments. Micro-CT scans (8 mum) were taken after use of each instrument
      to detect root filling residue in the coronal, middle and apical segment, and the
      retreatment time recorded. Residue, expressed as percentage of canal surface
      area, was compared between groups with t-tests, and within groups with repeated
      measures anova and Bonferroni-adjusted pairwise comparisons. Retreatment time was
      analysed with one-way anova. RESULTS: The percentage of sealer residue-coated
      canal surface was consistently highest (P < 0.001) in the apical third of canals,
      and it did not differ significantly between the two root filling groups. Stepwise
      enlargement from size 40 to 50 significantly decreased the amount of sealer
      residue in both groups (P < 0.001). Retreatment time did not differ significantly
      between groups. CONCLUSIONS: Both root fillings with ActivGP and GuttaFlow were
      removed with nickel-titanium rotary instruments. Enlargement of canals up to two
      sizes beyond the pre-retreatment size was necessary to minimize the amount of
      sealer remaining.

PMID- 20158532
TI  - Radio-opaque nanosized bioactive glass for potential root canal application:
      evaluation of radiopacity, bioactivity and alkaline capacity.
AB  - AIM: To produce novel nanosized bioactive glass particles with radio-opaque
      properties and high alkaline capacity and to evaluate their performance as a
      potential bioactive root canal dressing or filling material. METHODOLOGY: Flame
      spray-derived bioactive glass particles in the nanometre range were produced
      including bismuth oxide as a radiopacifier. Calcium hydroxide, barium sulphate
      and bismuth oxide served as controls. Corresponding materials were compressed to
      obtain dense specimens with increased alkaline capacity. Radiopacity was
      evaluated, and in vitro bioactivity was monitored using Raman spectroscopy and
      scanning electron microscopy. Leaching of bismuth was controlled using atomic
      absorption spectroscopy. RESULTS: Bioactive glass particles with up to 50 wt%
      bismuth oxide revealed radiopacity with an equivalent of 4.94-mm aluminium. The
      introduction of bismuth into the bioactive glass altered the alkaline capacity
      and the in vitro bioactivity only for high bismuth oxide quantities. Bismuth
      oxide leaching out of the glass matrix was hardly detectable. CONCLUSION:
      Bioactive glass can be modified with bismuth oxide to become radio-opaque.

PMID- 20158533
TI  - Vertical fracture of root filled teeth restored with posts: the effects of
      patient age and dentine thickness.
AB  - AIM: To determine whether patient age contributed to the fracture resistance of
      teeth subjected to root canal treatment and post placement. METHODOLOGY: Forty
      five single-rooted, single-canal human teeth were mounted, instrumented,
      obturated and prepared for a post. The teeth were divided into young (18 < or =
      age < or = 35) and old (60 < or = age) groups and subjected to cyclic loading
      until fracture; those reaching 200,000 cycles without undergoing failure were
      then subjected to static loading to fracture. Statistical differences between
      groups were examined using one-way anovas, and correlations were identified using
      Pearson's r; significance was established at P < or = 0.05. RESULTS: There was no
      significant difference between the two age groups in terms of the number of
      cycles to fracture (P > 0.05) or the load to fracture (P > 0.05). However, there
      was a significant correlation (P < or = 0.05) between the root fracture
      resistance and individual age, indicating that the susceptibility to root
      fracture increases significantly with increasing patient age. Also, the dentine
      thickness of roots that fractured was significantly less than those that did not
      (P = 0.04). CONCLUSION: Vertical root fracture of teeth receiving root canal
      treatment with posts is more likely to occur in the teeth of older patients (60+)
      and particularly in those with low dentine thickness.

PMID- 20158534
TI  - Cyclic fatigue of NiTi rotary instruments in a simulated apical abrupt curvature.
AB  - AIM: To evaluate the cyclic fatigue resistance of five NiTi rotary systems in an
      abrupt apical curvature. METHODOLOGY: Cyclic fatigue testing was performed in
      stainless-steel artificial canals with a 2-mm radius of curvature and an angle of
      curvature of 90 degrees constructed to the dimensions of the instruments tested.
      The middle of the simulated curvature was 2.5 mm from the tip of the instrument
      that was placed at full working length. All instruments were new and 25 mm in
      length. Ten ProTaper Universal F2 (Dentsply Maillefer, Ballaigues, Switzerland);
      FlexMaster (VDW, Munich, Germany) tip size 25, taper 0.06; Mtwo (Sweden &
      Martina, Padova, Italy) tip size 25, taper 0.06; ProFile tip size 25, taper 0.06
      from Dentsply Maillefer (Ballaigues, Switzerland); and ProFile tip size 25, taper
      0.06 from Dentsply Tulsa (Tulsa, OK, USA) were rotated passively at 300 rpm until
      fracture occurred, and the number of cycles to failure (NCF) recorded. Length of
      the fractured tip was measured. Data were analysed by one-way anova and Tukey HSD
      test to determine any statistical difference amongst groups. RESULTS: Mtwo had
      the highest fatigue resistance compared to the other instruments (NCF 124 +/- 25)
      (P < 0.001); there was no statistical difference between ProFile from the two
      different brands, although ProFile from Maillefer had the higher fatigue life
      (NCF 75 +/- 10) compared to ProFile from Tulsa (NCF 66 +/- 10). No difference was
      registered between FlexMaster (NCF 53 +/- 5) and ProFile from Tulsa; ProTaper F2
      had a significantly (P < 0.001) lower fatigue life compared to the other
      instruments tested (NCF 29 +/- 5). CONCLUSIONS: Lifespan registered for the
      instruments tested in an apical abrupt curvature was Mtwo > ProFile from
      Maillefer > ProFile from Tulsa > FlexMaster > ProTaper.

PMID- 20158535
TI  - Evaluation of the physical properties of an endodontic Portland cement
      incorporating alternative radiopacifiers used as root-end filling material.
AB  - AIM: To investigate the physical and chemical properties of Portland cement (PC)
      loaded with alternative radiopacifying materials for use as root-end filling
      materials in a mineral trioxide aggregate (MTA)-like system. METHODOLOGY:
      Portland cement loaded with barium sulphate, gold and silver/tin alloy was mixed
      with water, and the physical and chemical properties of the hydrated cements were
      evaluated. MTA and intermediate restorative material (IRM) were used as controls.
      The radiopacity was compared to the equivalent thickness of aluminium, and the
      setting time of the cements was assessed using an indentation technique. The
      compressive strength and the stress-strain relationship were determined at 28
      days. The stress-strain relationship was determined by monitoring the strain
      generated when the cement was subjected to compressive load. In addition, the pH
      was determined in water and simulated body fluid for a period of 28 days.
      RESULTS: The radiopacity of the cements using alternative radiopacifiers was
      comparable to MTA (P > 0.05). IRM demonstrated a higher radiopacity than all the
      materials tested (P < 0.05). All the cements with the exception of IRM exhibited
      an alkaline pH and had an extended setting time when compared to IRM. MTA had a
      longer setting time than the PC (P < 0.001), and its setting time was similar to
      the gold-loaded cement (P = 0.159). The addition of a radiopacifier retarded the
      setting time (P < 0.001) but did not have any effect on the compressive strength
      as all loaded cements had comparable strength to PC (P > 0.05). IRM was the
      weakest cement tested (P < 0.001). The cement loaded with gold radiopacifier had
      comparable strength to MTA (P = 1). The stress-strain relationship was linear for
      all the cements with IRM generating more strain on loading. CONCLUSIONS: Within
      the parameters set in this study, bismuth oxide in MTA can be replaced by gold or
      silver/tin alloy. The physical, mechanical and chemical properties of the cement
      replaced with alternative radiopacifiers were similar and comparable to ProRoot
      MTA.

PMID- 20158536
TI  - The effectiveness of passive ultrasonic irrigation on intraradicular Enterococcus
      faecalis biofilms in extracted single-rooted human teeth.
AB  - AIM: To compare the efficacy of passive ultrasonic irrigation with 1% sodium
      hypochlorite, with that of conventional syringe irrigation with 1% sodium
      hypochlorite, on intraradicular Enterococcus faecalis biofilms in extracted
      single-rooted human teeth. METHODOLOGY: Biofilms of E. faecalis (strain OMGS
      3202) were grown on the prepared root canal walls of 48 standardized root halves
      which had been longitudinally sectioned. Following reapproximation, the roots
      were divided into four groups of twelve. The two experimental groups were treated
      with conventional syringe irrigation with 1% sodium hypochlorite solution
      (experimental group A) and passive ultrasonic irrigation with 1% sodium
      hypochlorite solution (experimental group B). Of the two control groups, the
      first was treated with conventional syringe irrigation with sterile saline
      solution (control group C), whilst the second control group (D) received no
      irrigation. The root halves were processed for scanning electron microscopy.
      Three images (x 700), coronal, middle and apical, were taken of the twelve root
      halves in each of the four groups, using a standardized protocol. The images were
      randomized and biofilm coverage assessed independently by three calibrated
      examiners, using a four-point scoring system. RESULTS: There were no significant
      differences in the scores for remaining biofilm coverage between group A
      (conventional syringe irrigation with 1% sodium hypochlorite) and group B
      (passive ultrasonic irrigation with 1% sodium hypochlorite) at the three observed
      levels. There was a significant difference between both experimental groups
      (groups A and B) and group C (conventional syringe irrigation with sterile saline
      solution) (P < 0.001) at all three observed levels. CONCLUSIONS: Both
      conventional syringe irrigation and passive ultrasonic irrigation with 1% sodium
      hypochlorite were effective at completely removing intraradicular E. faecalis
      biofilms. Conventional syringe irrigation with sterile saline solution was only
      partially effective at removing the biofilms.

PMID- 20158537
TI  - Comparative cytotoxicity of five root canal sealers on cultured human periodontal
      ligament fibroblasts.
AB  - AIM: To evaluate the cytotoxicity of current root canal sealers to periodontal
      ligament (PDL) fibroblasts. METHODOLOGY: Five root canal sealers (Canals, Canals
      N, Topseal, Sealapex, Tubliseal) were prepared and placed into transwells. After
      initial setting for 1 h, the transwells with sealers were placed into cultured
      PDL fibroblasts. They were cultured for further 3 or 18 h. Morphological changes
      were observed. Cell viability was estimated by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-
      diphenyl-tetrazolium bromide (MTT) assay. RESULTS: Marked retraction and death of
      PDL fibroblasts were observed after exposure to Canals or Topseal for 3 h. A 3-h
      exposure of PDL fibroblasts to Tubliseal stimulated MTT reduction. Canals-N
      showed little cytotoxicity even after an exposure of 18 h. CONCLUSION: Canals was
      the most toxic sealer, followed by Topseal. Sealapex and Tubliseal had comparable
      and moderate cytotoxicity to PDL fibroblasts, whereas Canals-N showed little
      cytotoxicity. Exposure to Tubliseal may modulate MTT reduction in PDL
      fibroblasts. Canals-N had good biocompatibility.

PMID- 20158539
TI  - The TUNEL assay consistently underestimates DNA damage in human spermatozoa and
      is influenced by DNA compaction and cell vitality: development of an improved
      methodology.
AB  - The purpose of this study was to evaluate the terminal deoxynucleotidyl
      transferase dUTP nick end labelling (TUNEL) assay as a method for assessing DNA
      damage in human spermatozoa. The conventional assay was shown to be insensitive
      and unresponsive to the DNA fragmentation induced in human and mouse spermatozoa
      on exposure to Fenton reagents (H2O2 and Fe(2+) ). However, both time- and dose
      dependent responses could be readily detected if the chromatin was exposed to 2
      mm dithiothreitol (DTT) for 45 min prior to fixation. This modified version of
      the assay significantly enhanced the TUNEL signals generated by subpopulations of
      spermatozoa isolated on discontinuous Percoll gradients as well as the responses
      triggered by reagents (arachidonic acid and menadione) that are known to
      stimulate superoxide anion production by human spermatozoa. DTT exposure also
      improved the signals detected with chromomycin A3 (CMA3), a probe designed to
      determine the efficacy of chromatin protamination, and enhanced the correlation
      observed between this criterion of sperm quality and the TUNEL assay. Finally,
      the output of the TUNEL assay was found to be highly correlated with sperm
      vitality. The TUNEL methodology was therefore further refined to incorporate a
      vital stain that covalently bound to intracellular amine groups in non-viable
      cells. This tag remained associated with the spermatozoa during fixation and
      processing for the TUNEL assay so that ultimately, both DNA integrity and
      vitality could be simultaneously assessed in the same flow cytometry assay. The
      methods described in this article are simple and robust and should facilitate
      research into the causes of DNA damage in human spermatozoa.

PMID- 20158540
TI  - Penile haemodynamic changes in post-radical cystectomy patients.
AB  - The aim of this study was to assess the penile vascular changes in post-radical
      cystectomy patients. A prospective assessment took place between January 2003 and
      January 2005 of 45 potent men who underwent radical cystectomy and diversion for
      invasive bladder cancer. Nerve sparing (NS) technique was applied in 21 cases,
      while others were not subjected to NS (non-nerve sparing group; NNS = 24 cases).
      All patients were comparable in preoperative clinical and pathological
      parameters. A control arm was the preoperative normal indices of the same
      patients. Preoperative penile duplex ultrasounds (PDU) for all cases were carried
      out, and then follow-up 2, 6 and 12 months thereafter. On first postoperative
      visit, none of NS cases showed any arterial insufficiency, while two cases of NNS
      (8.3%) had peak systolic velocity (PSV) < 30 cm/sec. Moreover, all cases of both
      groups showed early increase of end diastolic velocity (EDV) > 5 cm/sec. In NS
      cystectomy group, the PSV showed statistically insignificant change [p > 0.05
      (mean: 53.6, cm/sec)]. Shortly after surgery, the EDV values increased, followed
      by gradually significant improvement (decrease in EDV values) in comparison with
      control state (mean: 5.9 cm/sec). On the other hand, the NNS cases showed
      statistically insignificant changes in PSV (mean: 49.3 cm/sec), with
      deterioration in EDV that did not improve with time, in contrast to NS cases
      (mean: 13.15 cm/sec). The main significant penile vascular changes were in EDV
      (venogenic mechanism) in post-cystectomy patients. There was a gradual
      progressive improvement in venogenic competence mechanism in NS cases with
      insignificant deterioration of arteriogenic mechanism in both groups (NS/NNS).

PMID- 20158541
TI  - A systematic review: Students with mental health problems--a growing problem.
AB  - The number of university students with a serious mental illness has risen
      significantly over the past few years. A systematic review was conducted that
      addressed emotional and or mental health problems of university students
      worldwide. In total, 572 articles were identified, of which 11 met inclusion
      criteria. Issues identified included types of problems experienced by students,
      how staff dealt with these students, barriers to seeking help, tools that
      facilitated help-seeking and epidemiological trends in the university student
      population. Recommendations include (i) providing better links between the
      university and external mental health providers, and (ii) increasing students'
      awareness of existing support services within and external to the university. As
      it is unrealistic to expect all academic staff to have the expertise required to
      deal with students with emotional problems, it is also recommended that (iii)
      policies and personnel with expertise in mental health are available to provide
      guidance for staff.

PMID- 20158542
TI  - Consumer participation: ensuring suicide postvention research counts for end
      users.
AB  - Primary health-care research is about working with those who have a vested
      interest in the outcomes of that research, including consumers, service providers
      and service organizations. This article describes how consumers were included in
      the research processes of a South Australian study into suicide postvention
      services, and illustrates important principles to consider when including
      consumers in research. A concurrent mixed-method approach facilitated the
      collection of mixed data through the application of questionnaires. The study was
      conducted in an Australian metropolitan area. Because of media releases, a large
      number of people rang to enquire and volunteer their participation. From over 200
      expressions of interest, 161 individuals participated. The participation of
      consumers in the research process ensured the findings were relevant for end
      users. A number of recommendations for the care and support of those bereaved
      through suicide were developed as a result.

PMID- 20158543
TI  - Prevalence of frailty on clinical wards: description and implications.
AB  - This paper describes the prevalence and frailty level of patients aged > or = 75
      years upon admission to various clinical wards. The data collection took place on
      five clinical wards of different clinical specialisms: Geriatric Centre,
      traumatology, pulmonology/rheumatology, internal medicine and surgical medicine.
      The Groningen Frailty Indicator was used to assess the frailty of newly admitted
      patients. The presence of number and kind of the various frailty indicators was
      different for the clinical wards, because of clinical diagnose, age and gender.
      On the Geriatric Centre, almost all patients were indicated as frail. On the
      other wards, 50-80% of the patients were indicated as frail with most frailty
      indicators on the scale 'psychosocial'. The study show a high prevalence of frail
      elderly on some wards and gives an indication of the various needs for other
      disciplines within the framework of the care for frail elderly people.

PMID- 20158544
TI  - Ethical values in caring encounters on a geriatric ward from the next of kin's
      perspective: an interview study.
AB  - The aim of this study was to identify and describe the governing ethical values
      that next of kin experience in interaction with nurses who care for elderly
      patients at a geriatric clinic. Interviews with 14 next of kin were conducted and
      data were analysed by constant comparative analysis. Four categories were
      identified: receiving, showing respect, facilitating participation and showing
      professionalism. These categories formed the basis of the core category: 'Being
      amenable', a concept identified in the next of kin's description of the ethical
      values that they and the elderly patients perceive in the caring encounter. Being
      amenable means that the nurses are guided by ethical values; taking into account
      the elderly patient and the next of kin. Nurses' focusing on elderly patients'
      well-being as a final criterion affects the next of kin and their experience of
      this fundamental condition for high-quality care seems to be fulfilled.

PMID- 20158545
TI  - Bedside nursing handover: a case study.
AB  - A case study of six wards in two hospitals was undertaken to describe the
      structures, processes and perceptions of outcomes of bedside handover in nursing.
      A total of 532 bedside handovers were observed and 34 interviews with nurses were
      conducted. Important structural elements related to the staff, patients, the
      handover sheet and the bedside chart. A number of processes before, during and
      after the handover were implemented. They included processes for managing
      patients and their visitors, sensitive information, and the flow of communication
      for variable shift starting times. Other key processes identified were the
      implementation of a safety scan and medication check. The situation, background,
      assessment and recommendations approach was used only in specific circumstances.
      Perceived outcomes were categorized as improving accuracy and service delivery,
      and promoting patient-centred care. Although the move to bedside handover is not
      the norm, it reflects a patient-centred approach.

PMID- 20158546
TI  - The influence of a health education programme on healthy lifestyles and practices
      among university students.
AB  - This study aimed at exploring the lifestyles of university students, the
      relationship between specific demographical variables and health practices and
      the role of training in improving these practices. An experimental and a
      comparison group were selected using the convenient sampling method. Two 5-day
      training programmes on healthy lifestyles were conducted. Self-reported
      behaviours of both groups were assessed before and after the programme. The
      results reflected slightly positive health practices related to the three
      behavioural categories with the type of diet being the highest and physical
      activity being the lowest. No significant differences were reflected in relation
      to the selected variables. A positive influence of training on improving health
      behaviours of university students related to the three behavioural categories was
      observed. Results suggest a similar course to be included as a university
      elective and students' involvement in available extra curricular activities be
      encouraged.

PMID- 20158547
TI  - Associations between psychosomatic symptoms in adolescence and mental health
      symptoms in early adulthood.
AB  - This longitudinal study explored associations between psychosomatic symptoms in
      adolescence and mental health symptoms in early adulthood. The baseline data were
      collected in 1996 from 14-year-old pupils (n = 235; 116 girls, 119 boys) at
      schools using a structured questionnaire that included a 14-item scale of
      psychosomatic symptoms. The follow-up data were collected in 2006 from the same
      persons at the age of 24 using the Symptom Checklist-90. Follow-up questionnaires
      were returned by 149 (63.4%) young adults (88 women and 61 men). Young adults who
      had many psychosomatic symptoms in adolescence suffered more often than the
      others from somatization and anxiety symptoms in early adulthood. In addition,
      women had more symptoms of depression and paranoid ideation, and men had more
      interpersonal sensitivity and psychotic symptoms. Psychosomatic symptoms in
      adolescence might be important signals of mental health and this should be taken
      seriously in school health and in general primary care.

PMID- 20158548
TI  - 'Caring? It's the little things we are not supposed to do anymore'.
AB  - This study explored the views of twenty-five qualified nurses in five hospitals
      to determine what they perceived as dominant values in clinical nursing work.
      Aspects of a grounded theory approach were used and this study formed the final
      one of three. The first two studies had student nurse samples and this study
      aimed to confirm and validate the data from the students' perceptions. The
      student nurses had implied that nurses communicated and 'cared' for patient's
      much less than they expected. Findings from this study reaffirm the students'
      perceptions and suggest that nurses may not be as caring as they would like to
      be. One significant issue to emerge, in conjunction with the realization that
      nurses were not being as caring as they would have liked, was that it mattered to
      them that caring was the 'little things' not 'supposed to be done anymore'.

PMID- 20158549
TI  - Caregiver burden of family members of persons living with HIV in Thailand.
AB  - Caregivers of people living with HIV (PLH) in Thailand face tremendous caregiver
      burden. This study examines complex ways in which caregivers' mental health
      affects their levels of caregiver burden. This study uses data from 409
      caregivers of PLH in northern and north-eastern Thailand. Multiple regression
      models were used to examine the predictors of caregiver burden. Depression was
      significantly associated with caregiver burden (P < 0.0001) and being HIV
      positive (P = 0.015). Inverse associations were observed between depression and
      quality of life (P < 0.0001) and caregiver burden and quality of life (P =
      0.004). Social support had direct positive association with caregiver's quality
      of life (P < 0.0001). Our findings underscore the complex relationship between
      caregiver burden, depression and HIV-status. Interventions that address the
      caregiver burden are urgently needed.

PMID- 20158550
TI  - Elderly persons' experiences of striving to receive care on their own terms in
      nursing homes.
AB  - Elderly persons' participation in and decisions about their own care need more
      attention. The aim of this study was to gain a deeper understanding of elderly
      persons' experiences of care and help, and how their lives change in nursing
      homes. Fifteen elderly persons living in four nursing homes were interviewed
      about their experiences of needing care and help in their daily life. The
      interviews were analysed using van Manen's phenomenological approach. Elderly
      persons' experiences of care and help were described as: a balance between sorrow
      and relief, a struggle to maintain control and connectedness, managing to live in
      the present and yet worrying about the future, and an attempt to hide one's
      vulnerability in order to be accepted and create an inner calm in an exposed
      situation. In conclusion, important issues were raised concerning elderly
      persons' perspectives on care and help in daily life in nursing homes.

PMID- 20158551
TI  - Experiences of the new role of advanced practice nurses in Swedish primary health
      care--a qualitative study.
AB  - Experiences of the new role of advanced practice nurses in Swedish primary health
      care-A qualitative study The aim of this study was to investigate and describe
      the experiences of the first advanced practice nurses (APNs), a new profession
      for Swedish health care, and of their supervising general practitioners (GPs),
      regarding the new role and scope of practice of APNs in primary health care.
      Individual interviews were conducted with the four first APNs and one focus group
      interview was conducted with five supervising physicians. The material was
      transcribed verbatim and analysed using latent content analysis. The respondents
      expressed confidence and trust in the new role of APNs. Some opposition to this
      new role from the GPs and other colleagues was observed, but was nonetheless
      overcome. The experiences of the APN role indicate that the new role is clearly
      demarcated from the role of physicians. The APNs were considered an extra
      resource for both the GPs and other nurses, which contributed to an increased
      availability of care for patients. The APN role requires an explicit definition
      and demarcation in relation to responsibility and roles among colleagues. Further
      development of the APN role presupposes the right to prescribe medication and
      order treatments, as well as an evaluation of patient, organizational and inter
      professional perspectives on the matter.

PMID- 20158552
TI  - An analysis of narratives to identify critical thinking contexts in psychiatric
      clinical practice.
AB  - The development of students' critical thinking abilities is one of the greatest
      challenges facing contemporary nursing educators. Nursing educators should know
      about what kind of contents or situations need critical thinking. The research
      was undertaken to identify the critical thinking contexts that nursing students
      confront in psychiatric clinical practices. Students were asked to document their
      everyday experience. The narratives were analysed and interpreted from the
      philosophical notion of hermeneutics. Four themes emerged as critical thinking
      contexts: anxiety, conflict, hyper-awareness, dilemmas. Writing narratives appear
      to provide opportunities for reflection in addition to facilitating critical
      thinking and communicative skills in students. Also, for the instructor,
      students' clinical narratives could provide insight to understand how students
      are thinking and to share student's personal difficulties.

PMID- 20158553
TI  - What is the matter with crushing pills and opening capsules?
AB  - This study aims to map out to what degree medication is being crushed and mixed
      into the patients' food and beverages and how often this practice included
      medication, which has a statement in the Norwegian pharmaceutical compendium that
      this should not be done (inappropriately altered medication (IAM)). Data from a
      total of 2108 patients in 151 wards in 65 nursing homes were collected. The data
      contained information about the kind of drugs the patient received, in which form
      it was given and how it was given. Patient characteristics and ward
      characteristics were also recorded. Twenty-three per cent were given at least one
      drug mixed into their food or beverages and 10% were given at least one IAM. This
      study shows a malpractice regarding one aspect of medication in nursing homes.
      Even though we need more knowledge, we know enough to take action to raise the
      quality of the administration of medicines in nursing homes.

PMID- 20158554
TI  - Perspectives of older persons on bathing and bathing disability: a qualitative
      study.
AB  - OBJECTIVES: To understand the bathing experiences, attitudes, and preferences of
      older persons in order to inform the development of effective patient-centered
      interventions. DESIGN: Qualitative study using the Grounded Theory framework.
      SETTING: In-depth, semistructured interviews were conducted in participants'
      homes. PARTICIPANTS: Twenty-three community-living persons aged 78 and older
      identified from the Precipitating Events Project (PEP). MEASUREMENTS: Open-ended
      questions about bathing habits, personal meaning and purpose of bathing,
      difficulties and concerns about bathing, preferences for independent bathing, and
      attitudes toward different types of bathing assistance. RESULTS: Three themes
      emerged: the importance and personal significance of bathing to older persons;
      variability in attitudes, preferences, and sources of bathing assistance; and
      older persons' anticipation of and responses to bathing disability. CONCLUSION:
      The bathing experiences described by study participants underscore the personal
      significance of bathing and the need to account for attitudes and preferences
      when designing bathing interventions. Quantitative disability assessments may not
      capture the bathing modifications made by older persons in anticipation of
      disability and may result in missed opportunities for early intervention.
      Findings from this study can be used to inform the development of targeted,
      patient-centered interventions that can subsequently be tested in clinical
      trials.

PMID- 20158555
TI  - Association between vitamin B12 levels and mortality in hospitalized older
      adults.
AB  - OBJECTIVES: To investigate the effect of various medications on vitamin B12
      status and the association between vitamin B12 levels and mortality. DESIGN:
      Retrospective cross-sectional study. SETTING: Four internal medicine departments
      and the geriatrics department at Kaplan Medical Center (KMC), Rehovot and
      Harzfeld Geriatrics Hospital, Gedera, Israel. PARTICIPANTS: One thousand five
      hundred seventy patients aged 65 and older hospitalized at the KMC and Hartzfeld
      Hospital in 2007. MEASUREMENTS: Blood vitamin B12 levels and demographic,
      clinical, and laboratory data obtained from electronic medical records. RESULTS:
      Vitamin B12 deficiency (<or=200 pmol/L) was found in 15% of older hospitalized
      patients. Fifty percent of the patients had high vitamin B12 levels (>or=350
      pmol/L), 68.2% of whom were aged 80 and older. Metformin use was clearly
      associated with lower vitamin B12 levels. In patients aged 65 and older, an
      inverse correlation was found between vitamin B12 levels and albumin, metformin,
      and angiotensin-converting enzyme (ACE) inhibitor use. Age, number of
      medications, and mortality were linearly correlated with vitamin B12 levels.
      CONCLUSION: Higher vitamin B12 levels were associated with greater mortality, but
      it is unclear whether vitamin B12 is a marker or a surrogate marker or even a
      substance that directly causes death. Further investigation is needed to clarify.

PMID- 20158556
TI  - Physicians' views on the importance of patient preferences in surrogate decision
      making.
AB  - OBJECTIVES: To explore the degree to which physicians report reliance on patient
      preferences when making medical decisions for hospitalized patients lacking
      decisional capacity. DESIGN: Cross-sectional survey. SETTING: One academic and
      two community hospitals in a single metropolitan area. PARTICIPANTS: Two hundred
      eighty-one physicians who recently cared for hospitalized adults. MEASUREMENTS: A
      self-administered survey addressing physicians' beliefs about ethical principles
      guiding surrogate decision-making and physicians' recent decision-making
      experiences. RESULTS: Overall, 72.6% of physicians identified a standard related
      to patient preferences as the most important ethical standard for surrogate
      decision-making (61.2% identified advanced directives and 11.4% substituted
      judgment). Of the 73.3% of physicians who reported recently making a surrogate
      decision, 81.8% reported that patient preferences were highly important in
      decision-making, although only 29.4% reported that patient preference was the
      most important factor in the decision. Physicians were significantly more likely
      to base decisions on patient preferences when the patient was in the intensive
      care unit (odds ratio (OR)=2.92, 95% confidence interval (CI)=1.15-7.45) and less
      likely when the patient was older (OR=0.76 for each decade of age, 95% CI=0.58
      0.99). The presence of a living will, prior discussions with the patient, and the
      physicians' beliefs about ethical guidelines did not significantly predict the
      physicians' reliance on patient preferences. CONCLUSION: Although a majority of
      physicians identified patient preferences as the most important general ethical
      guideline for surrogate decision-making, they relied on a variety of factors when
      making treatment decisions for a patient lacking decisional capacity.

PMID- 20158557
TI  - Poor functional status is an independent predictor of surgical site infections
      due to methicillin-resistant Staphylococcus aureus in older adults.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become a
      common surgical site infection (SSI) pathogen, particularly in older adults. Risk
      factors for MRSA SSI in elderly patients have not been described. METHODS: A
      nested case-control study was conducted. Patients were enrolled from seven study
      hospitals (one medical center and six community hospitals) between January 1,
      1998, and April 1, 2003. Risk factors for MRSA SSI were identified by comparing
      cases with two reference groups: uninfected surgical patients and patients with
      SSI due to methicillin-susceptible S. aureus (MSSA). Two separate multivariate
      models were created using logistic regression and then compared and contrasted.
      RESULTS: Eighty-six patients with MRSA and 64 with MSSA SSI were identified. One
      hundred sixty-seven uninfected surgical patients were selected. In multivariate
      analysis using uninfected surgical patients as controls, requiring assistance in
      three or more activities of daily living (ADLs) was an independent risk factor
      for MRSA SSI (odds ratio (OR)=2.73, 95% confidence interval (CI)=1.16-6.46).
      Using patients with MSSA SSIs as a reference group, requiring assistance in three
      or more ADLs was also a significant predictor for MRSA SSI (OR=3.78, 95% CI=1.43
      9.98) in multivariate analysis. Other independent predictors included Charlson
      score, wound class, and surgical duration. Lack of independence in ADLs was an
      independent risk factor for MRSA SSI in elderly patients in both models.
      CONCLUSION: Poor functional status (requiring assistance in >or=3 ADLs) was
      specifically associated with MRSA SSI. Functional status is an objective, readily
      available variable that can be used to stratify patients at risk for MRSA SSI.

PMID- 20158558
TI  - Homocysteine and mobility in older adults.
AB  - OBJECTIVES: To determine the influence of homocysteine on mobility decline in
      older adults. DESIGN: Prospective cohort. SETTING: Einstein Aging Study,
      community-based aging study. PARTICIPANTS: Five hundred seventy-four older adults
      without dementia (mean age 80.2 +/- 5.4, 61% women). MEASUREMENTS: Mobility
      decline defined using gait velocity measurements at baseline and annual follow-up
      visits. Linear mixed effects models were used to adjust for age, sex, education,
      and other potential confounders. RESULTS: Higher homocysteine levels were
      associated with slower gait velocity at baseline. Adjusted for age, sex, and
      education, a one-unit increase in baseline log homocysteine levels was associated
      with a 2.95-cm/s faster mobility decline per year (P=.01) over a median follow-up
      of 1.4 years. The 140 subjects in the highest quartile of homocysteine had a
      faster rate of mobility decline (1.75 cm/s per year faster, P=.01) than the 434
      subjects in the lowest three quartiles of homocysteine (<or=15 micromol/L). The
      association between homocysteine and mobility decline remained robust even after
      adjusting for multiple confounders and accounting for the presence of clinical
      gait abnormalities. CONCLUSION: Higher homocysteine levels are associated with
      greater risk of mobility decline in community-residing older adults.

PMID- 20158559
TI  - Can we improve the identification of ventricular scar to guide substrate-based
      ventricular tachycardia ablation?

PMID- 20158560
TI  - Correlative anatomy for the electrophysiologist: ablation for atrial
      fibrillation. Part II: regional anatomy of the atria and relevance to damage of
      adjacent structures during AF ablation.
AB  - Ablation procedures for atrial fibrillation have become an established and
      increasingly used option for managing patients with symptomatic arrhythmia. The
      anatomic structures relevant to the pathogenesis of atrial fibrillation and
      ablation procedures are varied and include the pulmonary veins, other thoracic
      veins, the left atrial myocardium, and autonomic ganglia. Exact regional anatomic
      knowledge of these structures is essential to allow correlation with fluoroscopy
      and electrograms and, importantly, to avoid complications from damage of adjacent
      structures within the chest. We present this information as a series of 2
      articles. In a prior issue, we have discussed the thoracic vein anatomy relevant
      to paroxysmal atrial fibrillation. In the present article, we focus on the atria
      themselves, the autonomic ganglia, and anatomic issues relevant for minimizing
      complications during atrial fibrillation ablation.

PMID- 20158561
TI  - Prevalence and clinical characteristics associated with left atrial appendage
      thrombus in fully anticoagulated patients undergoing catheter-directed atrial
      fibrillation ablation.
AB  - INTRODUCTION: Catheter-directed atrial fibrillation (AF) ablation is
      contraindicated among patients with left atrial appendage (LAA) thrombus. The
      prevalence of LAA thrombus among fully anticoagulated patients undergoing AF
      ablation is unknown. METHODS AND RESULTS: We retrospectively evaluated the
      prevalence of LAA thrombus among 192 consecutive patients undergoing AF ablation
      between July 2006 and January 2009. Seven of 192 patients (3.6%) had evidence of
      thrombus on transesophageal echocardiogram (TEE) despite being fully
      anticoagulated on warfarin (international normalized ratio [INR] 2-3) for 4
      consecutive weeks prior to echocardiogram. Univariate analysis demonstrated that
      structural heart disease, large left atrial dimension, and number of AF ablations
      were associated with thrombus. Three patients with thrombus had paroxysmal AF
      with normal LV function. CONCLUSION: Despite full anticoagulation, 3.6% of
      patients undergoing AF ablation had LAA thrombus. We recommend that all patients,
      regardless of LV function or left atrial size, should undergo preprocedural TEE
      to exclude the presence of LAA thrombus.

PMID- 20158562
TI  - Correlative anatomy for the electrophysiologist: ablation for atrial
      fibrillation. Part I: pulmonary vein ostia, superior vena cava, vein of Marshall.
AB  - Ablation procedures for atrial fibrillation (AF) have become an established and
      increasingly used option for managing patients with symptomatic arrhythmia. The
      anatomic structures relevant to the pathogenesis of AF and ablation procedures
      are varied and include the pulmonary veins (PVs), other thoracic veins, the left
      atrial myocardium, and autonomic ganglia. Exact regional anatomic knowledge of
      these structures is essential to allow correlation with fluoroscopy and
      electrograms, and, importantly, to avoid complications from damage of adjacent
      structures within the chest. We have presented this information in a 2-part
      series. In the present article, we examine the general anatomic characteristics
      of the PVs, superior vena cava, and vein of Marshall. Features of particular
      relevance for the invasive electrophysiologist are pointed out. In a subsequent
      article, we discuss the regional anatomy of the left and right atria and anatomic
      considerations in preventing complications during AF ablation.

PMID- 20158563
TI  - Ablation of severe drug-resistant tachyarrhythmia during pregnancy.
AB  - AIMS: The goal of this study was to describe mapping and ablation of severe
      arrhythmias during pregnancy, with minimum or no X-ray exposure. Treatment of
      tachyarrhythmia in pregnancy is a clinical problem. Pharmacotherapy entails a
      risk of adverse effects and is unsuccessful in some patients. Radiofrequency
      ablation has been performed rarely, because of fetal X-ray exposure and potential
      maternal and fetus complications. GROUP AND METHOD: Mapping and ablation was
      performed in 9 women (age 24-34 years) at 12-38th week of pregnancy. Three had
      permanent junctional reciprocating tachycardia, and 2 had incessant atrial
      tachycardia. Four of them had left ventricular ejection fraction < or =45%. One
      patient had atrioventricular nodal reciprocating tachycardia requiring
      cardioversion. Three patients had Wolff-Parkinson-White syndrome. Two of them had
      atrial fibrillation with ventricular rate 300 bpm and 1 had atrioventricular
      tachycardia 300 bpm. Fetal echocardiography was performed before and after the
      procedure. RESULTS: Three women had an electroanatomic map and ablation done
      without X-ray exposure. The mean fluoroscopy time in the whole group was 42 +/-
      37 seconds. The mean procedure time was 56 +/- 18 minutes. After the procedure,
      all women and fetuses were in good condition. After a mean period of 43 +/- 23
      months follow up (FU), all patients were free of arrhythmia without complications
      related to ablation either in the mothers or children. CONCLUSION: Ablation can
      be performed safely with no or minimal radiation exposure during pregnancy. In
      the setting of malignant, drug-resistant arrhythmia, ablation may be considered a
      therapeutic option in selected cases.

PMID- 20158564
TI  - A long conduction time in the coronary sinus: has mitral isthmus line been
      blocked?

PMID- 20158566
TI  - Re: Synchronous ventricular pacing without crossing the tricuspid valve or
      entering the coronary sinus--preliminary results.

PMID- 20158567
TI  - Gene therapy in Alzheimer's disease - potential for disease modification.
AB  - Alzheimer's disease (AD) is the major cause of dementia in the elderly, leading
      to memory loss and cognitive decline. The mechanism underlying onset of the
      disease has not been fully elucidated. However, characteristic pathological
      manifestations include extracellular accumulation and aggregation of the amyloid
      beta-peptide (Abeta) into plaques and intracellular accumulation and aggregation
      of hyperphosphorylated tau, forming neurofibrillary tangles. Despite extensive
      research worldwide, no disease modifying treatment is yet available. In this
      review, we focus on gene therapy as a potential treatment for AD, and summarize
      recent work in the field, ranging from proof-of-concept studies in animal models
      to clinical trials. The multifactorial causes of AD offer a variety of possible
      targets for gene therapy, including two neurotrophic growth factors, nerve growth
      factor and brain-derived neurotrophic factor, Abeta-degrading enzymes, such as
      neprilysin, endothelin-converting enzyme and cathepsin B, and AD associated
      apolipoprotein E. This review also discusses advantages and drawbacks of various
      rapidly developing virus-mediated gene delivery techniques for gene therapy.
      Finally, approaches aiming at down-regulating amyloid precursor protein (APP) and
      beta-site APP cleaving enzyme 1 levels by means of siRNA-mediated knockdown are
      briefly summarized. Overall, the prospects appear hopeful that gene therapy has
      the potential to be a disease modifying treatment for AD.

PMID- 20158568
TI  - The role of caspase-2 in stress-induced apoptosis.
AB  - Caspase-2 is the most evolutionarily conserved of all the caspases, yet it has a
      poorly defined role in apoptotic pathways. This is mainly due to a dearth of
      techniques to determine the activation status of caspase-2 and the lack of an
      abnormal phenotype in caspase-2 deficient mice. Nevertheless, emerging evidence
      suggests that caspase-2 may have important functions in a number of stress
      induced cell death pathways, in cell cycle maintenance and regulation of tumour
      progression. This review discusses recent advances that have been made to help
      elucidate the true role of this elusive caspase and the potential contribution of
      caspase-2 to the pathology of human diseases including cancer.

PMID- 20158569
TI  - Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC cocultures.
AB  - Inflammatory pathways are involved in the development of atherosclerosis.
      Interaction of vessel wall cells and invading monocytes by cytokines may trigger
      local inflammatory processes. 3-Hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (statins) are standard medications used in cardiovascular diseases.
      They are thought to have anti-inflammatory capacities, in addition to their lipid
      lowering effects. We investigated the anti-inflammatory effect of statins in the
      cytokine-mediated-interaction-model of human vascular smooth muscle cells (SMC)
      and human mononuclear cells (MNC). In this atherosclerosis-related inflammatory
      model LPS (lipopolysaccharide, endotoxin), as well as high mobility group box 1
      stimulation resulted in synergistic (i.e. over-additive) IL-6 (interleukin-6)
      production as measured in ELISA. Recombinant IL-1, tumour necrosis factor-alpha
      and IL-6 mediated the synergistic IL-6 production. The standard anti-inflammatory
      drugs aspirin and indomethacin (Indo) reduced the synergistic IL-6 production by
      60%. Simvastatin, atorvastatin, fluvastatin or pravastatin reduced the IL-6
      production by 53%, 50%, 64% and 60%, respectively. The inhibition by the statins
      was dose dependent. Combination of statins with aspirin and/or Indo resulted in
      complete inhibition of the synergistic IL-6 production. The same inhibitors
      blocked STAT3 phosphorylation, providing evidence for an autocrine role of IL-6
      in the synergism. MNC from volunteers after 5 day aspirin or simvastatin
      administration showed no decreased IL-6 production, probably due to drug removal
      during MNC isolation. Taken together, the data show that anti-inflammatory
      functions (here shown for statins) can be sensitively and reproducibly determined
      in this novel SMC/MNC coculture model. These data implicate that statins have the
      capacity to affect atherosclerosis by regulating cytokine-mediated innate
      inflammatory pathways in the vessel wall.

PMID- 20158570
TI  - Roles of phospholipase D in phorbol myristate acetate-stimulated neutrophil
      respiratory burst.
AB  - The phorbol myristate acetate (PMA) stimulated nutrophil respiratory burst has
      been considered to simply involve the activation of protein kinase C (PKC).
      However, the PLD activity was also increased by 10-fold in human neutrophils
      stimulated with 100 nM PMA. Unexpectedly, U73122, an inhibitor of phospholipase
      C, was found to significantly inhibit PMA-stimulated respiratory burst in human
      neutrophils. U73122 at the concentrations, which were sufficient to inhibit the
      respiratory burst completely, caused partial inhibition of the PLD activity but
      no inhibition on PKC translocation and activation, suggesting that PLD activity
      is also required in PMA-stimulated respiratory burst. Using 1-butanol, a PLD
      substrate, to block phosphatidic acid (PA) generation, the PMA-stimulated
      neutrophil respiratory burst was also partially inhibited, further indicating
      that PLD activation, possibly its hydrolytic product PA and diacylglycerol (DAG),
      is involved in PMA-stimulated respiratory burst. Since GF109203X, an inhibitor of
      PKC that could completely inhibit the respiratory burst in PMA-stimulated
      neutrophils, also caused certain suppression of PLD activation, it may suggest
      that PLD activation in PMA-stimulated neutrophils might be, to some extent, PKC
      dependent. To further study whether PLD contributes to the PMA stimulated
      respiratory burst through itself or its hydrolytic product, 1,2-dioctanoyl-sn
      glycerol, an analogue of DAG , was used to prime cells at low concentration, and
      it reversed the inhibition of PMA-stimulated respiratory burst by U73122. The
      results indicate that U73122 may act as an inhibitor of PLD, and PLD activation
      is required in PMA-stimulated respiratory burst.

PMID- 20158571
TI  - MafA promotes the reprogramming of placenta-derived multipotent stem cells into
      pancreatic islets-like and insulin+ cells.
AB  - MafA is a pancreatic transcriptional factor that controls beta-cell-specific
      transcription of the insulin gene. However, the role of MafA in the regulation of
      pancreatic transdifferentiation and reprogramming in human stem cells is still
      unclear. In this study, we investigate the role of MafA in placenta-derived
      multipotent stem cells (PDMSCs) that constitutively expressed Oct-4 and Nanog.
      PDMSCs were isolated and transfected with MafA using a lentivector. Our results
      showed that overexpression of MafA in PDMSCs significantly up-regulated the
      expression of pancreatic development-related genes (Sox17, Foxa2, Pdx1 and Ngn3).
      Microarray analysis suggested that the gene expression profile of MafA
      overexpressing PDMSCs was similar to that of pancreas and islet tissues. MafA
      increased the expression levels of the mRNAs of NKx2.2, Glut2, insulin, glucagons
      and somatostatin, and further facilitated the differentiation of PDMSCs into
      insulin(+) cells. The glucose-stimulated responses to insulin and c-peptide
      production in MafA-overexpressing PDMSCs were significantly higher than in PDMSCs
      with vector control. Our results indicated that MafA-overexpressing PDMSCs were
      more resistant to oxidative damage and oxidative damage-induced apoptosis than
      PDMSCs carrying the vector control were. Importantly, the expression of MafA in
      PDMSCs xenotransplanted into immunocompromised mice improved the restoration of
      blood insulin levels to control values and greatly prolonged the survival of
      graft cells in immunocompromised mice with STZ-induced diabetes. In summary,
      these data suggest that MafA plays a novel role in the reprogramming of stem
      cells into pancreatic beta-progenitors, promotes the islet-like characteristics
      of PDMSCs, as well as functionally enhances insulin production to restore the
      regulation of blood glucose levels in transplanted grafts.

PMID- 20158572
TI  - Enhanced platelet adhesion induces angiogenesis in intestinal inflammation and
      inflammatory bowel disease microvasculature.
AB  - Although angiogenesis is viewed as a fundamental component of inflammatory bowel
      disease (IBD) pathogenesis, we presently lack a thorough knowledge of the cell
      type(s) involved in its induction and maintenance in the inflamed intestinal
      mucosa. This study aimed to determine whether platelet (PLT) adhesion to inflamed
      intestinal endothelial cells of human origin may favour angiogenesis.
      Unstimulated or thrombin-activated human PLT were overlaid on resting or tumour
      necrosis factor (TNF)-alpha-treated human intestinal microvascular endothelial
      cells (HIMEC), in the presence or absence of blocking antibodies to either
      vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)
      1, integrin alpha(v)beta(3) , tissue factor (TF) or fractalkine (FKN). PLT
      adhesion to HIMEC was evaluated by fluorescence microscopy, and release of
      angiogenic factors (VEGF and soluble CD40L) was measured by ELISA. A matrigel
      tubule formation assay was used to estimate PLT capacity to induce angiogenesis
      after co-culturing with HIMEC. TNF-alpha up-regulated ICAM-1, alpha(v)beta(3) and
      FKN expression on HIMEC. When thrombin-activated PLT were co-cultured with
      unstimulated HIMEC, PLT adhesion increased significantly, and this response was
      further enhanced by HIMEC activation with TNF-alpha. PLT adhesion to HIMEC was
      VCAM-1 and TF independent but ICAM-1, FKN and integrin alpha(v)beta(3) dependent.
      VEGF and sCD40L were undetectable in HIMEC cultures either before or after TNF
      alpha stimulation. By contrast, VEGF and sCD40L release significantly increased
      when resting or activated PLT were co-cultured with TNF-alpha-pre-treated HIMEC.
      These effects were much more pronounced when PLT were derived from IBD patients.
      Importantly, thrombin-activated PLT promoted tubule formation in HIMEC, a
      functional estimate of their angiogenic potential. In conclusion, PLT adhesion to
      TNF-alpha-pre-treated HIMEC is mediated by ICAM-1, FKN and alpha(v)beta(3) , and
      is associated with VEGF and sCD40L release. These findings suggest that inflamed
      HIMEC may recruit PLT which, upon release of pro-angiogenic factors, actively
      contribute to inflammation-induced angiogenesis.

PMID- 20158573
TI  - Oncologist's/haematologist's view on the roles of pathologists for molecular
      targeted cancer therapy.
AB  - In the past two decades there has been a tremendous increase in the understanding
      of the molecular basis of human malignancies. In a variety of neoplasms, specific
      molecular markers became part of disease classifications and are now routinely
      used to define specific entities. Molecular analyses discriminate prognostic
      groups, guide differential treatment strategies and identify targets for
      molecular defined cancer therapy. A battery of new drugs has been developed to
      specifically inhibit oncogenic pathways. For an increasing number of solid and
      haematological malignancies, the availability of molecular targeted drugs has
      fundamentally changed treatment algorithms. However, the diagnostic, prognostic
      and therapeutic impact of selected molecular markers is still limited in many
      cases. After all, the success of a molecular targeted therapy is clearly
      determined by the significance of the targeted structure for the biology of
      cancer and the ability of the malignant cell to evade specific inhibition.

PMID- 20158576
TI  - Amoebic gill disease in hatchery-reared ayu, Plecoglossus altivelis (Temminck &
      Schlegel), in Japan is caused by Neoparamoeba perurans.

PMID- 20158574
TI  - Inter-connection between mitochondria and HIFs.
AB  - The transcription factors hypoxia inducible factors 1 and 2 (HIF-1 and HIF-2)
      regulate multiple responses to physiological hypoxia such as transcription of the
      hormone erythropoietin to enhance red blood cell proliferation, vascular
      endothelial growth factor to promote angiogenesis and glycolytic enzymes to
      increase glycolysis. Recent studies indicate that HIFs also regulate
      mitochondrial respiration and mitochondrial oxidative stress. Interestingly,
      mitochondrial metabolism, respiration and oxidative stress also regulate
      activation of HIFs. In this review, we examine the evidence that mitochondria and
      HIFs are intimately connected to regulate each other resulting in appropriate
      responses to hypoxia.

PMID- 20158577
TI  - Impact of yellow head virus outbreaks in the whiteleg shrimp, Penaeus vannamei
      (Boone), in Thailand.
AB  - Yellow head virus (YHV) is known as a major pathogen in the black tiger shrimp,
      Penaeus (Penaeus) monodon. It can also cause serious mortality in farmed whiteleg
      shrimp, Penaeus (Litopenaeus) vannamei. However, there is no published
      information on the economic and/or production impact of the disease in P.
      vannamei. Shrimp with gross signs of YHV disease (faded body colour and 60-70%
      mortality) were observed in 20 study farms rearing P. vannamei in the central
      part of Thailand from the end of 2007 through early 2008. The estimated economic
      loss for these farms according to the Thai Animal Aquaculture Association was
      approximately US$3 million. Detailed sequence analysis of RT-PCR amplicons from
      shrimp in all the study ponds revealed the presence of YHV Type 1b (YHV-1b) alone
      (characterized by a 162-bp deletion in the ORF3 region encoding the structural
      gene for gp116) and the absence of YHV Type 1a (YHV-1a), the original YHV type
      reported from Thailand. Despite the large 162-bp deletion (= 54 deduced amino
      acids) in the gp116 structural gene, histopathology of YHV-1b infections was
      identical to that of YHV-1a infections, and electron microscopy revealed that YHV
      1b virions were morphologically indistinguishable from those previously reported
      for YHV-1a. In addition, an existing commercial RT-PCR detection kit and an
      immunochromatographic test strip for the detection of YHV were proven to have
      been valid tests for both YHV-1b and YHV-1a. The source of the virus for these
      outbreaks was unlikely to have been the post-larvae used to stock the ponds, as
      they were derived from domesticated specific pathogen-free stocks free of YHV.
      Thus, it is possible that they originated from an unknown, natural reservoir.

PMID- 20158575
TI  - Temperament and the environment in the etiology of childhood anxiety.
AB  - Anxiety disorders are prevalent throughout childhood and adolescence. As such,
      identifying the factors and mechanisms that precede, maintain, or exacerbate
      anxiety disorders is essential for the development of empirically based
      prevention and intervention programs. The current review focuses on child
      temperament (i.e., behavioral inhibition) and the child's environment, including
      parenting, childcare, and peer relationships, as these factors have been linked
      to internalizing problems and anxiety diagnoses. Research programs are needed
      that examine the associations between the environment and anxiety in
      temperamentally at-risk populations. In order to be successful, early
      intervention and prevention programs require a more detailed analysis of the
      interplay between various environmental contexts, both distal and proximal to the
      child, and the child's temperamental reactivity to novelty and threat.
      Furthermore, conducting these investigations across multiple levels of analysis
      in large-scale, longitudinal samples would be an important addition to the
      literature on the developmental psychopathology of anxiety.

PMID- 20158578
TI  - Salmonid alphavirus (SAV) and pancreas disease (PD) in Atlantic salmon, Salmo
      salar L., in freshwater and seawater sites in Norway from 2006 to 2008.
AB  - A cohort study was initiated in the spring of 2006 to investigate epidemiological
      aspects and pathogenesis of salmonid alphavirus (SAV) subtype 3 infections and
      pancreas disease (PD). The aims were to assess involvement of the freshwater
      production phase, the extent and frequency of subclinical infections and to
      follow PD-affected populations throughout the entire seawater production cycle,
      as well as investigate possible risk factors for PD outbreaks. Fish groups from
      46 different Atlantic salmon freshwater sites in six counties were sampled once
      prior to seawater transfer and followed onto their seawater sites. A total of 51
      Atlantic salmon seawater sites were included, and fish groups were sampled three
      times during the seawater production phase. SAV subtype 3 was not identified by
      real-time RT-PCR from samples collected in the freshwater phase, nor were any SAV
      neutralizing antibodies or histopathological changes consistent with PD. In the
      seawater phase, SAV was detected in samples from 23 of 36 (63.9%) studied sites
      located within the endemic region. No SAV subtype 3 was detected in samples from
      seawater sites located outside the endemic region. The cumulative incidence of PD
      during the production cycle amongst sites with SAV detected was 87% (20 of 23
      sites). Average fish weight at time of PD diagnosis ranged from 461 to 5978 g,
      because of a wide variation in the timing of disease occurrence throughout the
      production cycle. Mortality levels following a PD diagnosis varied greatly
      between populations. The mean percentage mortality was 6.9% (+/-7.06) (range 0.7
      26.9), while the mean duration of increased mortality following PD diagnosis was
      2.8 months (+/-1.11) (range 1-6).

PMID- 20158579
TI  - Dried leaves of Rosmarinus officinalis as a treatment for streptococcosis in
      tilapia.
AB  - Dietary application of dried Rosmarinus officinalis (rosemary) leaves as a
      treatment for streptococcal infection was studied in tilapia, Oreochromis sp.
      Feeding with dried rosemary leaves significantly reduced mortality following
      infection with Streptococcus iniae: 44% mortality in the group fed 8% rosemary,
      similar to oxytetracycline treatment (43% mortality), and significantly lower
      than the control (65%). Dietary administration of 16% rosemary significantly
      reduced mortality because of Streptococcus agalactiae infection in 44 g fish (62%
      and 76% in 16% rosemary and control, respectively), but not in a similar
      experiment conducted with 5.5 g fish. The antibacterial effect of rosemary on S.
      iniae was studied. Activity of rosemary cultivar Israel was reduced during the
      winter, but there was no significant change in cultivars Oranit and Star. Storage
      of powdered rosemary leaves at 50 degrees C resulted in fourfold and eightfold
      higher MIC(24 h) values after 3 and 4.5 months, respectively. Storage at -20
      degrees C, 4 degrees C and 25 degrees C and autoclaving (120 degrees C) each
      resulted in a twofold increase in MIC(24 h). Repeated exposures of S. iniae to
      rosemary did not affect minimal inhibitory concentration, suggesting no
      development of resistance to rosemary.

PMID- 20158580
TI  - Viral haemorrhagic septicaemia virus IVb experimental infection of rainbow trout,
      Oncorhynchus mykiss (Walbaum), and fathead minnow, Pimphales promelas
      (Rafinesque).
AB  - Viral haemorrhagic septicaemia virus (VHSV) in the Great Lakes has had a dramatic
      impact on fish husbandry because of the implications of the presence of a
      reportable disease. Experimental infections with VHSV IVb were conducted in
      rainbow trout, Oncorhynchus mykiss (Walbaum), and fathead minnows, Pimphales
      promelas (Rafinesque), to examine their susceptibility and the clinical impact of
      infection. Triplicate groups of rainbow trout (n = 40) were injected
      intraperitoneally (i.p.) with 100 microL 10(6.5)50% tissue culture infective
      doses (TCID(50)) or waterborne exposed to graded doses (10(4.5), 10(6.5), and
      10(8.5) TCID(50) mL(-1)) of VHSV IVb. Duplicate groups of fathead minnows (n =
      15) were i.p. injected with (10(6.5) TCID(50) 100 microL) or waterborne exposed
      (10(6.5) TCID(50) mL(-1)). All experiments were performed with single-pass well
      water maintained at 12 degrees C. Following either i.p. or waterborne exposure,
      VHSV RNA was detectable in both rainbow trout and fathead minnows by nested
      reverse transcription polymerase chain reaction (nRT-PCR) as early as 4-7 days
      post-infection (p.i.). Infected fathead minnow and rainbow trout exhibited
      lesions characteristic of VHS at 9 and 15 days p.i., respectively. Route of
      exposure had little effect on the onset of clinical signs. Cumulative mean
      mortality in rainbow trout was 4.4%, 2.6%, 2.6% and less than 1% in the i.p.,
      high, medium and low dose waterborne exposures, respectively. Cumulative average
      mortality of 50% and 13% occurred in i.p. and waterborne-exposed fathead minnows,
      respectively. VHSV was detected from pooled rainbow trout tissue by RT-PCR and
      virus isolation at 38 days p.i., but not at 74 days p.i., regardless of the
      exposure route. Immunohistochemistry (IHC) with a rabbit antibody to VHSV IVb
      revealed the viral tissue tropisms following infection, with the identification
      of viral antigen in myocardium and necrotic branchial epithelium of both species
      and in gonadal tissue of fathead minnows. Rainbow trout, but not fathead minnows,
      are relatively refractory to experimental infection with VHSV IVb.

PMID- 20158581
TI  - Molecular detection of betanodavirus from the farmed fish, Platax orbicularis
      (Forsskal) (Ephippidae), in French Polynesia.

PMID- 20158582
TI  - Viral haemorrhagic septicaemia virus IVb inactivation by ultraviolet light, and
      storage viability at 4 and -20 degrees C.

PMID- 20158583
TI  - A comparative epizootiologic study of the two fish-pathogenic serovars of Vibrio
      vulnificus biotype 2.
AB  - Vibrio vulnificus biotype 2 is subdivided into two main serovars, serovar E, able
      to infect fish and humans, and serovar A, only virulent for fish. Serovar E
      emerged in 1976 as the causative agent of a haemorrhagic septicaemia (warm-water
      vibriosis) affecting eels cultured in brackish water. Serovar A emerged in 2000
      in freshwater-cultured eels vaccinated against serovar E, causing warm-water
      vibriosis with fish showing a haemorrhagic intestine as the main differential
      sign. The aim of the present work was to compare the disease caused by both
      serovars in terms of transmission routes, portals of entry and host range.
      Results of bath, patch-contact and oral-anal challenges demonstrated that both
      serovars spread through water and infect healthy eels, serovar A entering mainly
      by the anus and serovar E by the gills. The course of the disease under
      laboratory conditions was similar for both serovars in terms of transmission and
      dependence of degree of virulence on water parameters (temperature and salinity).
      However, the decrease in degree of virulence in fresh water was significantly
      greater in serovar E than in serovar A. Finally, both serovars proved pathogenic
      for tilapia, sea bass and rainbow trout, but not for sea bream, with significant
      differences in degree of virulence only in rainbow trout. In conclusion, serovar
      A seems to represent a new antigenic form of V. vulnificus biotype 2 with an
      unusual portal of entry and is better adapted to fresh water than serovar E.

PMID- 20158584
TI  - Efficacy and safety of 1064-nm Q-switched Nd:YAG laser with low fluence for
      keloids and hypertrophic scars.
AB  - BACKGROUND: Several treatment modalities using laser devices have been used for
      the treatment of keloids and hypertrophic scars with various therapeutic
      outcomes. OBJECTIVE: The purpose of this study was to describe the efficacy and
      safety of 1064-nm Q-switched (QS) Nd:YAG laser with low fluence on keloids and
      hypertrophic scars. METHODS: Keloids and hypertrophic scars located at 21
      anatomic sites in 12 Korean patients (10 men and 2 women; mean age 23.8 years,
      range 21-33) were treated using 1064-nm QS Nd:YAG laser with low fluence at 1-2
      week intervals. Treatment settings were 1.8-2.2 J/cm(2), 7-mm spot size and 5-6
      passes with appropriate overlapping. RESULTS: Follow-up data collected 3 months
      after the final treatment revealed decreases in the mean score for the following
      lesion characteristics: pigmentation from 1.8 to 1.2; vascularity from 1.4 to
      1.0; pliability from 3.0 to 2.0 and height from 2.3 to 1.8. The modified
      Vancouver General Hospital Burn Scar Assessment score decreased from 8.6 to 5.9
      (P < 0.0001). Observed side-effects were a mild prickling sensation during
      treatment, and mild post-treatment erythema, both of which resolved within few
      hours. CONCLUSION: Our results demonstrate that QS Nd:YAG laser with low fluence
      may be used for the treatment of keloids and hypertrophic scars.

PMID- 20158585
TI  - HPA-suppressive effects of aqueous clobetasol propionate in the treatment of
      patients with oral lichen planus.
AB  - BACKGROUND: Oral topical corticosteroids have potential to produce inhibition of
      the hypothalamus-pituitary-adrenal (HPA) axis. OBJECTIVE: To assess whether
      clobetasol propionate (CP) in aqueous solution causes HPA inhibition. PATIENTS
      AND METHODS: Sixty-two patients with oral lichen planus or oral lichenoid lesions
      presenting with severe lesions were treated with topical oral 0.05% CP plus
      100,000 IU/cm(3) nystatin in aqueous solution. Initial treatment of three 5-min
      mouthwashes (10 mL) daily was reduced, when the response was deemed complete or
      excellent, to a maintenance treatment of one 5-min mouthwash on alternate days
      for 6 months; treatment was then withdrawn and patients were followed up for 1
      year. HPA function was assessed by plasma cortisol measurement and
      adrenocorticotropin (ACTH) stimulation at the end of the initial and maintenance
      treatment regimens. RESULTS: The HPA axis was more frequently inhibited during
      initial (53/62; 85.5%) vs. maintenance (2/49; 4%) regimens of aqueous CP.
      LIMITATIONS: In patients with morning plasma cortisol levels between 3 and 18
      microg/dL, a normal result for the ACTH stimulation test only moderately reduces
      the possibility that a patient has secondary adrenal insufficiency. This can be
      considered a minor limitation in our study, as only three patients required
      additional assessment with the ACTH stimulation test. CONCLUSIONS: Hypothalamus
      pituitary-adrenal inhibition is substantial during initial treatment with aqueous
      CP three times daily.

PMID- 20158586
TI  - Efficacy of sulfasalazine in the treatment of generalized lichen planus:
      randomized double-blinded clinical trial on 52 patients.
AB  - BACKGROUND: Oral sulfasalazine has been reported to be effective in patients with
      idiopathic cutaneous lichen planus (LP). OBJECTIVES: Our purpose was to evaluate
      the efficacy of this drug in the treatment of generalized cutaneous lichen planus
      (GLP). In this study, we evaluated the effectiveness of the anti-inflammatory
      drug sulfasalazine for the treatment of GLP. METHODS: A total of 52 patients with
      GLP presenting at the outpatient clinic were enrolled in this double-blind,
      randomized, placebo-controlled, prospective study. Of these patients, 44
      completed the period of study. The patients were randomly divided into two
      groups. One group received placebo and the other was given sulfasalazine maximum
      2.5 g/day. The patients were evaluated at the third and sixth weeks of treatment
      for improvement rate and occurrence of complications. RESULTS: After 6 weeks of
      treatment, the rate of cutaneous lesions improvement was 9.6% (two patients) in
      the placebo group and 82.6% (19 patients) in the sulfasalazine group. The
      improvement rate of pruritus was 14.3% in the placebo group and 91.3% in the
      sulfasalazine group. Side-effects which were mild and tolerable were detected in
      30.7% of patients, but three patients left the study because of side effects.
      Most of the reported side-effects included gastrointestinal upset and headache.
      CONCLUSIONS: Statistically, sulfasalazine was more effective than placebo in
      reducing cutaneous lesions and improving pruritus after 6 weeks of treatment.
      According to our study, sulfasalazine is a relatively safe and effective
      treatment option and may be an alternative therapy for the treatment of
      generalized lichen planus.

PMID- 20158587
TI  - Sentinel lymph node biopsy in melanoma patients.
AB  - Appropriate surgical management of regional lymph nodes is critical in patients
      with cutaneous melanoma. The use of intraoperative lymphatic mapping and sentinel
      lymph node biopsy (SLNB) has increased significantly in the past decade. SLNB is
      performed as minimally invasive procedure that provides accurate staging of
      melanoma patients with no clinically detectable nodal disease. In many melanoma
      units across the world, it became the standard for detection of occult regional
      node metastasis in patients with intermediate-thickness primary melanoma. Use of
      SLNB in patients with thin melanomas is still under evaluation. Although SLNB has
      been established as staging procedure in melanoma patients, its therapeutic role
      is still not clear. Large-scale ongoing randomized trials should elucidate
      whether SLNB with complete lymphadenectomy has a survival benefit in melanoma
      patients with early lymph node metastases compared to 'watch-and-wait' policy
      (observation).

PMID- 20158588
TI  - Atypical fibroxanthoma: a series of 25 cases.
AB  - OBJECTIVE: Atypical fibroxanthoma is a rare mesenchymal tumour of skin that
      develops on skin of elderly patients. We analysed our patients with atypical
      fibroxanthoma over the last 8 years. PATIENTS AND METHODS: We analysed the
      pathology files of our hospital for the period 2001-2009. In all cases, histology
      and immunohistology were performed. Data on co-morbidities, treatment and outcome
      were obtained. RESULTS: We identified 25 patients (except two female patients,
      the rest were men) aged 52-95 years (mean: 79.5 years; standard deviation +/-
      9.06 years). All tumours were localized in the head and neck region, except a
      single tumour on the shoulder. Fourteen patients had a cancer history, six had
      actinic keratoses or Bowen's disease (n = 1). Five patients had cardiac surgery
      or pacemaker, one each had a renal transplant, systemic sarcoidosis or non
      Hodgkin's lymphoma. Medical history was positive for radiotherapy or chemotherapy
      in four patients. Histology showed a spindle-shaped dermal and subcutaneous
      tumour growth intermingled with multinucleated giant cells. The phenotype of
      tumour cells was vimentin-positive, but S100- and keratin-negative. Some tumours
      showed a focal expression of CD68. Complete microhistographic controlled surgery
      ('Mohs like') was possible in all cases followed by mesh-graft transplantation in
      three patients. Eighteen patients showed a complete remission. Four patients had
      a relapse within 2 years of follow-up treated by surgery. One patient is still
      under radiotherapy. All patients with a safety margin of 2 cm had no recurrence
      or relapse during follow-up. CONCLUSIONS: Micrographic controlled surgery with
      wide 2 cm safety margins is the treatment of choice. A regular follow-up for the
      next 5 years is recommended.

PMID- 20158589
TI  - Twice-weekly treatment with tacrolimus 0.03% ointment in children with atopic
      dermatitis: clinical efficacy and economic impact over 12 months.
AB  - BACKGROUND: Rational healthcare decision-making based on clinical and economic
      evidence is essential to provide the best possible care for patients with atopic
      dermatitis (AD). OBJECTIVE: To evaluate treatment outcomes, resource use and cost
      associated with twice-weekly tacrolimus 0.03% ointment treatment vs. standard
      flare-only therapy in children with moderate-to-severe AD. METHODS: In a pan
      European, Phase III multicentre randomized clinical trial, children with mild-to
      severe AD were randomized to 0.03% tacrolimus ointment or vehicle twice weekly
      for 12 months. Disease flares were treated using open-label tacrolimus 0.03%
      ointment twice daily. Clinical efficacy data were evaluated in a subgroup of 153
      children with moderate-to-severe AD, with resource use data--collected
      prospectively using caregiver questionnaires--available from 146 children. Pooled
      costs of resource use were determined using German unit cost data. Direct and
      indirect costs were considered from third-party payer, patient and caregiver, and
      societal perspectives. RESULTS: Twice-weekly tacrolimus ointment reduced the
      number of flares compared with standard therapy (P < 0.001) and prolonged time to
      first flare (146 vs. 17 days, P < 0.001). Mean +/- SD annual costs per patient
      for standard and twice-weekly therapy respectively were 2002 euro +/- 2315 vs.
      1571 euro+/- 1122 for severe AD and 1136 euro +/- 1494 vs. 1233 euro +/- 1507 for
      moderate AD. CONCLUSIONS: In children with AD, twice-weekly treatment with
      tacrolimus 0.03% ointment reduces the number of flares and prolongs time spent
      free from flares with no additional cost in children with moderate AD, and may be
      cost-saving in those with severe AD.

PMID- 20158591
TI  - A two-level model for evidence evaluation in the presence of zeros.
AB  - Likelihood ratios (LRs) provide a natural way of computing the value of evidence
      under competing propositions. We propose LR models for classification and
      comparison that extend the ideas of Aitken, Zadora, and Lucy and Aitken and Lucy
      to include consideration of zeros. Instead of substituting zeros by a small
      value, we view the presence of zeros as informative and model it using Bernoulli
      distributions. The proposed models are used for evaluation of forensic glass
      (comparison and classification problem) and paint data (comparison problem). Two
      hundred and sixty-four glass samples were analyzed by scanning electron
      microscopy, coupled with an energy dispersive X-ray spectrometer method and 36
      acrylic topcoat paint samples by pyrolysis gas chromatography hyphened with mass
      spectrometer method. The proposed LR model gave very satisfactory results for the
      glass comparison problem and for most of the classification tasks for glass.
      Results of comparison of paints were also highly satisfactory, with only 3.0%
      false positive answers and 2.8% false negative answers.

PMID- 20158590
TI  - Predicting phenotype from genotype: normal pigmentation.
AB  - Genetic information in forensic studies is largely limited to CODIS data and the
      ability to match samples and assign them to an individual. However, there are
      circumstances, in which a given DNA sample does not match anyone in the CODIS
      database, and no other information about the donor is available. In this study,
      we determined 75 SNPs in 24 genes (previously implicated in human or animal
      pigmentation studies) for the analysis of single- and multi-locus associations
      with hair, skin, and eye color in 789 individuals of various ethnic backgrounds.
      Using multiple linear regression modeling, five SNPs in five genes were found to
      account for large proportions of pigmentation variation in hair, skin, and eyes
      in our across-population analyses. Thus, these models may be of predictive value
      to determine an individual's pigmentation type from a forensic sample,
      independent of ethnic origin.

PMID- 20158592
TI  - Identification from chest x-rays: reliability of bone density patterns of the
      humerus.
AB  - A critical review of Kahana and Hiss' study on identification from bone
      trabecular pattern and a test of their method conducted on the humerus are
      presented. Bone trabecular pattern was studied through the generation of a
      numerical file representing the gray scale. Using the correlation coefficient,
      several pairwise comparisons between numerical files were performed. The test
      gave nearly 30% of incorrect exclusions (the method did not recognize couples of
      radiographs belonging to the same subject) and 50% of misidentifications (the
      method recognized couples of radiographs belonging to different subjects, as
      belonging to the same subject); therefore, this research shows that at the
      present time, it is not possible to safely quantify identification through bone
      density patterns, of the proximal humerus taken from thoracic X-rays. Thus, an
      "easy"-but dangerous-use of trabecular density patterns on this specific type of
      radiogram as an identification method should be currently avoided.

PMID- 20158593
TI  - Comparison of the performance of two methods for height estimation.
AB  - In the case study, two methods of performing body height measurements in images
      are compared based on projective geometry and 3D modeling of the crime scene.
      Accuracy and stability of height estimations are tested using reconstruction
      images of test persons of known height. Given unchanged camera settings,
      predictions of both methods are accurate. However, as the camera had been moved
      in the case, new vanishing points and camera matches had to be created for the
      reconstruction images. 3D modeling still yielded accurate and stable estimations.
      Projective geometry produced incorrect predictions for test persons and unstable
      intervals for questioned persons. The latter is probably caused by the straight
      lines in the field of view being hard to discern. With the quality of material
      presented, which is representative for our case practice, using vanishing points
      may thus yield unstable results. The results underline the importance of
      performing validation experiments in casework.

PMID- 20158594
TI  - Emotional experiences and motivating factors associated with fingerprint
      analysis.
AB  - In this study, we investigated the emotional and motivational factors involved in
      fingerprint analysis in day-to-day routine case work and in significant and
      harrowing criminal investigations. Thematic analysis was performed on interviews
      with 13 experienced fingerprint examiners from a variety of law enforcement
      agencies. The data revealed factors relating to job satisfaction and the use of
      skill. Individual satisfaction related to catching criminals was observed; this
      was most notable in solving high profile, serious, or long-running cases. There
      were positive emotional effects associated with matching fingerprints and
      apparent fear of making errors. Finally, we found evidence for a need of
      cognitive closure in fingerprint examiner decision-making.

PMID- 20158595
TI  - Death of a 10-month-old boy after exposure to ethylmorphine.
AB  - Ethylmorphine, an opiate that is partially metabolized to morphine, is a common
      ingredient in antitussive preparations. We present a case where a 10-month-old
      boy was administered ethylmorphine in the evening and found dead in bed the
      following morning. Postmortem toxicological analyses of heart blood by gas
      chromatography-mass spectrometry and liquid chromatography-mass spectrometry
      revealed the presence of ethylmorphine and morphine at concentrations of 0.17 muM
      (0.054 mg/L) and 0.090 muM (0.026 mg/L), respectively. CYP2D6 genotyping showed
      that the deceased had an extensive metabolizer genotype, signifying a "normal"
      capacity for metabolizing ethylmorphine to morphine. The autopsy report concluded
      that death was caused by a combination of opiate-induced sedation and weakening
      of respiratory drive, a respiratory infection, and a sleeping position that could
      have impeded breathing. This is the first case report where the death of an
      infant has been linked to ethylmorphine ingestion.

PMID- 20158596
TI  - Trends in converted firearms in England & Wales as Identified by the National
      Firearms Forensic Intelligence Database (NFFID) between September 2003 and
      September 2008.
AB  - The National Firearms Forensic Intelligence Database (NFFID (c) Crown Copyright
      2003-2008) was developed by The Forensic Science Service (FSS) as an
      investigative tool for collating and comparing information from items submitted
      to the FSS to provide intelligence reports for the police and relevant government
      agencies. The purpose of these intelligence reports was to highlight current
      firearm and ammunition trends and their distribution within the country. This
      study reviews all the trends that have been highlighted by NFFID between
      September 2003 and September 2008. A total of 8887 guns of all types have been
      submitted to the FSS over the last 5 years, where an average of 21% of annual
      submissions are converted weapons. The makes, models, and modes of conversion of
      these weapons are described in detail. The number of trends identified by NFFID
      shows that this has been a valuable tool in the analysis of firearms-related
      crime.

PMID- 20158597
TI  - Comparison of GSR composition occurring at different locations around the firing
      position.
AB  - Variations in gunshot residue (GSR) compositions are used in the reconstruction
      of shooting incidents. In this study, GSR samples taken from seven different
      locations around and in the firearm were collected and analyzed using scanning
      electron microscopy/energy dispersive X-ray analysis. Four different types of
      ammunition were applied. Very low correlations were found when different
      ammunition were used. This clearly shows that it is possible to differentiate
      between ammunition types. When the same ammunition was used, high correlations
      were found between samples taken from external positions (such as hands of
      shooter, bullet-entrance holes) but poor correlation was found between internal
      samples (such as firearm barrel, cartridge case) and external samples. A high
      degree of association was found between samples that simulated victim and
      shooter. These findings clearly demonstrate that GSR comparison studies are
      meaningful but care needs to be taken when choosing suitable exhibits. External
      samples (such as hands of shooter, bullet-entrance holes) are more suitable
      candidates than internal samples (barrel of the firearm, cartridge case).

PMID- 20158598
TI  - Disability assessment in temporomandibular disorders and masticatory system
      rehabilitation.
AB  - The consequences of a disease or condition such as temporomandibular disorders
      (TMD) include functional limitation and psychosocial disability. These two
      concepts refer to the individual's experience of limitations in function
      associated with the affected part of the body and to disarray in one's life,
      respectively. Models of disability emphasize the individual's self-report in
      describing these states and the centrality of these concepts as part of the
      disease and illness process. However, assessment approaches typically used in
      medicine and especially in dentistry do not yet routinely include these domains.
      TMD, as a musculoskeletal pain condition, can clearly lead to both limitation and
      disability, and the available evidence suggests that dentofacial disorders can
      also lead to both consequences. The relatively low contribution of disease
      impairment (measured changes in function through objective tests), however, to
      the reported limitation or disability in either TMD or dentofacial disorders
      remains complex and poorly understood. This article reviews the overall model of
      disablement, the necessary properties of measures to assess disablement, the
      present state of knowledge about these concepts, and what measures should be
      considered as part of routine assessment.

PMID- 20158599
TI  - Ageing and surface EMG activity patterns of masticatory muscles.
AB  - The purpose of this study was to evaluate the influence of age on the
      electromyographic activity of masticatory muscles. All volunteers were Brazilian,
      fully dentate (except for Group I - mixed dentition), Caucasian, aged 7-80, and
      divided into five groups: I (7-12 years), II (13-20 years), III (21-40 years), IV
      (41-60 years) and V (61-80 years). Except for Group V, which comprised nine women
      and eight men, all groups were equally divided with respect to gender (20 M/20
      F). Surface electromyographic records of masticatory muscles were obtained at
      rest and during maximal voluntary contraction, right and left laterality, maximal
      jaw protrusion and maximal clenching in the intercuspal position. Statistically
      significant differences (P < 0.05) were found in all clinical conditions among
      the different age groups. Considerably different patterns of muscle activation
      were found across ages, with greater electromyographic activity in children and
      youth, and decreasing from adults to aged people.

PMID- 20158600
TI  - Acquired facial palsy with hypertension secondary to Guillain-Barre syndrome.
AB  - Most cases of facial nerve paresis are idiopathic (Bell's palsy). However, rare
      and potentially dangerous conditions may present in this manner. We report 2
      children presenting with unilateral lower motor neuron facial nerve palsy and
      hypertension. A diagnosis of Guillain-Barre syndrome was made in both; literature
      linking facial nerve palsy in childhood with hypertension and Guillain-Barre
      syndrome is reviewed.

PMID- 20158601
TI  - von Willebrand factor activation, granzyme-B and thrombocytopenia in
      meningococcal disease.
AB  - SUMMARY BACKGROUND: During invasive meningococcal disease, severe
      thrombocytopenia is strongly associated with a poor outcome. OBJECTIVES: In order
      to elucidate the pathophysiological mechanism behind the development of
      thrombocytopenia, we studied the role of von Willebrand factor (VWF) in
      meningococcal disease. PATIENTS/METHODS: Thirty-two children with severe
      meningococcal disease admitted to our university hospital were included in this
      study. VWF and related parameters were measured and results were correlated with
      the development of shock and thrombocytopenia. RESULTS: At admission, all
      patients had increased levels of (active) VWF and VWF propeptide. The highest VWF
      propeptide levels were observed in patients with shock, indicating acute
      endothelial activation. Although VWF propeptide levels in patients with shock,
      with or without thrombocytopenia, were similar, increased active VWF was
      significantly lower in patients with thrombocytopenia as compared with patients
      without thrombocytopenia. ADAMTS13 was moderately decreased. However, the VWF
      multimeric pattern was minimally increased. We assume that these findings are
      explained by VWF consumption and perhaps by granzyme B (GrB). In vitro
      experiments showed that GrB is able to cleave VWF multimers in plasma, whereas
      GrB was high in patients with shock, who developed thrombocytopenia. CONCLUSIONS:
      Our results demonstrate that consumption of VWF, derived from endothelial cells,
      could be a key feature of meningococcal disease and primary to the development of
      thrombocytopenia during shock.

PMID- 20158602
TI  - The burden of hepatitis C in Sweden: a national study of inpatient care.
AB  - The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that
      serious liver complications (SLC) would increase in the 2000s. The aim of this
      study was to analyse the burden of HCV-associated inpatient care in Sweden, to
      demonstrate the changes over time and to compare the findings with a noninfected
      population. The HCV-cohort (n: 43,000) was identified from the national
      surveillance database 1990-2006, and then linked to national registers to produce
      an age-, sex-, and region-matched noninfected comparison population (n: 215,000)
      and to obtain information on demographics, cancers, inpatient care and
      prescriptions. Cox regression was used to estimate the likelihood (hazard ratios)
      for admission to hospital in the HCV compared with the noninfected cohort. The
      hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for
      liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission
      rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age-
      and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the
      rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45%
      of all episodes were for psychiatric, mostly drug-related, care. Inpatient care
      for SLC increased in the 2000s. To conclude, drug-related care was common in the
      HCV-infected cohort, the demand for liver-related care was very high, and SLC
      increased notably in the 2000s, indicating that the burden of inpatient care from
      serious liver disease in HCV-infected individuals in Sweden is an increasing
      problem.

PMID- 20158603
TI  - Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in
      the daily routine treatment of patients with chronic hepatitis C in Germany: the
      PRACTICE study.
AB  - In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV)
      results in a sustained virological response (SVR) in around half of hepatitis C
      virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This
      study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus
      RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic
      hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of
      3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or
      peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the
      large, multicentre, observational PRACTICE study. Collected data included
      baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early
      virological response, end of treatment response and SVR were 76.6%, 75.7% and
      52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In
      patients matched by baseline parameters, 59.9% of patients in Group A and 55.9%
      in Group B achieved an SVR (P < or = 0.051). In genotype 1-infected patients
      matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and
      43.7% for Group A and Group B, respectively (P < or = 0.047); when matched by
      baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%,
      respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients
      discontinued treatment (P < or = 0.0001). The efficacy and tolerability of
      peginterferon plus RBV in this large cohort of patients treated in routine daily
      practice was similar to that in randomized clinical trials. In matched pairs
      analyses, more patients achieved an SVR with peginterferon alfa-2a compared with
      peginterferon alfa-2b.

PMID- 20158605
TI  - Characterization of Yersinia enterocolitica 4/O:3 isolates from tonsils of
      Bavarian slaughter pigs.
AB  - AIMS: Yersinia enterocolitica 4/O:3 isolates of slaughter pigs originating from
      different farms were characterized to study the distribution of different
      genotypes at farm. A correlation between the genotypes and the resistance
      patterns was also examined. METHODS AND RESULTS: Hundred and eighty-seven ail
      positive Y. enterocolitica 4/O:3 isolates recovered from pigs originating from 31
      Bavarian farms in 2000, 2003 and 2004 were characterized. PFGE using NotI, ApaI
      and XhoI enzymes revealed 31 genotypes. The most common genotype was found in 13%
      of the pigs. From most farms (71%), only one genotype was found. Some genotypes
      were found during different years. Low resistance was noted to streptomycin (9%),
      sulphamethoxazole (9%), amoxicillin/clavulanic acid (5%) and tetracycline (1%) by
      agar disc diffusion method. CONCLUSIONS: Several genotypes were found. Some
      genotypes were widely distributed and persisted for years. Farm-specific
      genotypes may exist. No clear relation between the genotypes and antimicrobial
      patterns was found. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides
      data on the genetic diversity of Bavarian pig strains and antimicrobial
      resistance. It may be of interest for other countries where Y. enterocolitica
      strains are genotyped to get more information about the strain distribution of
      this pathogen.

PMID- 20158604
TI  - Prevalence of chronic hepatitis B virus infection among patients in the HIV
      Outpatient Study, 1996-2007.
AB  - Coinfection with hepatitis B virus (HBV) is an important and preventable cause of
      chronic liver disease among HIV-infected patients. We calculated the prevalence
      of chronic HBV infection annually from 1996 to 2007 by age, gender,
      race/ethnicity, and HIV transmission risk in a multisite observational cohort
      study of HIV-infected patients. Prevalence of chronic HBV infection was
      calculated as the number of patients with a positive HBsAg or detectable HBV DNA
      divided by the number of patients tested using either one of these assays. Among
      4467 (59%) patients tested for chronic HBV infection from a total of 7618
      patients active during 1996-2007, median age was 38.5 years, 77% were men, 49%
      were white, 35% were black, 13% were Hispanic, and 53% were men who had sex with
      men (MSM). Overall, 8.4% tested positive for HBsAg or detectable HBV DNA. Annual
      chronic HBV prevalence during 1996-2007 ranged from 7.8% to 8.6% without a
      statistically significant trend. Overall, prevalence was greater among men
      compared with women; among whites, blacks, and persons of other race compared
      with Hispanics; among MSM compared with injection drug users and high-risk
      heterosexuals; and among patients aged 35-44 years compared with younger or older
      patients. MSM constituted the greatest fraction (63-72%) of all HBV-infected
      patients in the HIV Outpatient Study (HOPS) over the period. Of eligible
      patients, 5.8%, 23.4%, and 31.6% had received at least one dose of HBV vaccine by
      years 1996, 2002, and 2007, respectively. Despite the availability of an
      effective HBV vaccine for over two decades and long-standing recommendations for
      immunization of persons (with or without HIV infection) at risk for HBV, the
      prevalence of chronic HBV infection in this study has been largely unchanged over
      the past decade among patients in all groups, and overall was 20 times as high as
      the national population prevalence.

PMID- 20158606
TI  - A chimeric vector for efficient chromosomal modification in Enterococcus faecalis
      and other lactic acid bacteria.
AB  - AIM: To construct a chimeric vector named pBVGh for quickly generating gene
      modifications in Enterococcus faecalis. METHODS AND RESULTS: The constructed
      plasmid pBVGh carries the pG(+)host replicon (a thermosensitive (TS) derivative
      of pWV01), allowing a simple generation of mutants by growing colonies first at
      the permissive temperature and then switching the culture to the nonpermissive
      temperature. Additionally, this vector facilitates the screening of mutants by a
      rapid colorimetric blue-white discrimination of plasmid-free bacteria.
      CONCLUSIONS: The pBVGh vector allows a straightforward inactivation or
      modification of target genes as well as a fast selection of enterococcal mutant
      strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The broad range of the TS replicon
      utilized in this plasmid permits the easy establishment and the efficient
      generation of food-grade mutant strains in Ent. faecalis and several other gram
      positive bacteria.

PMID- 20158607
TI  - Lack of O-polysaccharide enhances biofilm formation by Bradyrhizobium japonicum.
AB  - AIMS: To reveal the effects of the O-polysaccharide antigen of Bradyrhizobium
      japonicum LPS on biofilm formation and motility. METHODS AND RESULTS: Wild type
      and O-antigen-deficient mutant strains of B. japonicum were tested for biofilm
      formation on polyvinyl chloride (PVC) surfaces and motility on semi-solid (0.3%)
      agar media. After 7 days of incubation, the amount of biofilms formed by the
      mutant was c. 3.5-fold greater than that of the wild type. Unlike biofilm
      formation, the motility assay revealed that the mutant strain was less motile
      than the wild type. CONCLUSIONS: This study shows enhanced biofilm formation and
      decreased motility by the O-antigen-deficient mutant, suggesting that the lack of
      the O-polysaccharide of the rhizobial LPS is associated with biofilm-forming
      ability and movement. SIGNIFICANCE AND IMPACT OF THE STUDY: LPS plays an
      important role in both pathogenic and beneficial bacteria. It has also been
      reported that LPS deficiency negatively affects biofilm formation. However, our
      results demonstrate that the O-antigen-deficient mutant enhances biofilm
      formation, presumably through a significant increase in hydrophobicity. It is
      notable that the hydrophobicity of cell walls might be a key regulator in
      controlling biofilm development in B. japonicum.

PMID- 20158608
TI  - Triclosan inhibition of mycobacterial InhA in Saccharomyces cerevisiae: yeast
      mitochondria as a novel platform for in vivo antimycolate assays.
AB  - AIMS: To demonstrate the suitability of yeast to act as a novel biotechnological
      platform for conducting in vivo inhibition assays using drugs with low efficacies
      towards their mycobacterial targets, such as occurs in the situation with
      triclosan and InhA. METHODS AND RESULTS: A surrogate yeast host represented by
      Saccharomyces cerevisiae etr1Delta cells lacking Etr1p, the 2-trans-enoyl
      thioester reductase of mitochondrial type 2 fatty acid synthase (FASII), was
      designed to rely on the Mycobacterium tuberculosis FASII enzyme InhA. Although
      InhA is 10,000 times less sensitive to the antimicrobial drug triclosan than is
      bacterial FabI, the respiratory growth of yeast cells depending on InhA was
      severely affected on glycerol medium containing triclosan. CONCLUSIONS: The yeast
      system could detect enzyme inhibition despite the use of a drug with only low
      efficacy. SIGNIFICANCE AND IMPACT OF THE STUDY: Tuberculosis affects a third of
      the human population, and InhA is a major drug target for combating this disease.
      InhA is inhibited by isoniazid, but triclosan-derived compounds are presently
      being developed as antimycolates. A demonstration of triclosan inhibition of InhA
      in yeast represents a meaningful variation in studying this effect in
      mycobacteria, because it occurred without the potentially confusing aspects of
      perturbing protein-protein interactions which are presumed vital to mycobacterial
      FASII, inactivating other important enzymes or eliciting a dedicated
      transcriptional response in Myco. tuberculosis.

PMID- 20158609
TI  - Does local sympathetic atrophy contribute to splanchnic vasodilation in portal
      hypertension?

PMID- 20158610
TI  - Avoiding and managing lamivudine resistance in chronic hepatitis B: current
      approaches and potential strategies including pegylated interferon.
AB  - Since its approval for the treatment of chronic hepatitis B in 1998, lamivudine
      (LAM) has been used extensively throughout the world, because of its relatively
      low costs and favourable tolerability. However, clinical trials and cohort
      studies have demonstrated that a high rate of resistance to this drug develops
      and, as a result, it is no longer included as a first-line therapy in most
      current treatment guidelines. Nevertheless, because of its low cost, this drug
      continues to be used in many countries and the pool of patients who have
      developed resistance to LAM continues to increase. Thus, there is a clear need to
      develop coherent management strategies to treat such patients as well as limit
      the emergence of resistance in the first instance. The purpose of this review is
      to highlight the need to aim for long-term treatment success while limiting the
      emergence of drug resistance and its consequences for the future. In addition to
      add-on/switch strategies with other nucleos(t)ide analogs, currently available
      data suggest that interferon-based therapies, with their potential to induce a
      sustained response, are worthy of consideration not only for reducing de novo
      resistance but as an option for the management of those patients in whom drug
      resistance has already developed.

PMID- 20158611
TI  - Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia
      inducible factor and transforming growth factor-beta-dependent mechanisms.
AB  - BACKGROUND/AIMS: During development of liver fibrosis, an important source of
      myofibroblasts is hepatocytes, which differentiate into myofibroblasts by
      epithelial to mesenchymal transition (EMT). In epithelial tumours and kidney
      fibrosis, hypoxia, through activation of hypoxia-inducible factors (HIFs), is an
      important stimulus of EMT. Our recent studies demonstrated that HIF-1alpha is
      important for the development of liver fibrosis. Accordingly, the hypothesis was
      tested that hypoxia stimulates hepatocyte EMT by a HIF-dependent mechanism.
      METHODS: Primary mouse hepatocytes were exposed to room air or 1% oxygen and EMT
      evaluated. In addition, bile duct ligations (BDLs) were performed in control and
      HIF-1alpha-deficient mice and EMT quantified. RESULTS: Exposure of hepatocytes to
      1% oxygen increased expression of alpha-smooth muscle actin, vimentin, Snail and
      fibroblast-specific protein-1 (FSP-1). Levels of E-cadherin and zona occludens-1
      were decreased. Upregulation of FSP-1 and Snail by hypoxia was completely
      prevented in HIF-1beta-deficient hepatocytes and by pretreatment with SB431542, a
      transforming growth factor-beta (TGF-beta) receptor inhibitor. HIFs promoted TGF
      beta-dependent EMT by stimulating activation of latent TGF-beta1. To determine
      whether HIF-1alpha contributes to EMT in the liver during the development of
      fibrosis, control and HIF-1alpha-deficient mice were subjected to BDL. FSP-1 was
      increased to a greater extent in the livers of control mice when compared with
      HIF-1alpha-deficient mice. CONCLUSIONS: Results from these studies demonstrate
      that hypoxia stimulates hepatocyte EMT by a HIF and TGF-beta-dependent mechanism.
      Furthermore, these studies suggest that HIF-1alpha is important for EMT in the
      liver during the development of fibrosis.

PMID- 20158612
TI  - The IbpA and IbpB small heat-shock proteins are substrates of the AAA+ Lon
      protease.
AB  - Small heat-shock proteins (sHSPs) are a widely conserved family of molecular
      chaperones, all containing a conserved alpha-crystallin domain flanked by
      variable N- and C-terminal tails. We report that IbpA and IbpB, the sHSPs of
      Escherichia coli, are substrates for the AAA+ Lon protease. This ATP-fueled
      enzyme degraded purified IbpA substantially more slowly than purified IbpB, and
      we demonstrate that this disparity is a consequence of differences in maximal Lon
      degradation rates and not in substrate affinity. Interestingly, however, IbpB
      stimulated Lon degradation of IbpA both in vitro and in vivo. Furthermore,
      although the variable N- and C-terminal tails of the Ibps were dispensable for
      proteolytic recognition, these tails contain critical determinants that control
      the maximal rate of Lon degradation. Finally, we show that E. coli Lon degrades
      variants of human alpha-crystallin, indicating that Lon recognizes conserved
      determinants in the folded alpha-crystallin domain itself. These results suggest
      a novel mode for Lon substrate recognition and provide a highly suggestive link
      between the degradation and sHSP branches of the protein quality-control network.

PMID- 20158613
TI  - Chemokine-cleaving Streptococcus pyogenes protease SpyCEP is necessary and
      sufficient for bacterial dissemination within soft tissues and the respiratory
      tract.
AB  - SpyCEP is a Streptococcus pyogenes protease that cleaves CXCL8/IL-8 and its
      activity is associated with human invasive disease severity. We investigated the
      role of SpyCEP in S. pyogenes necrotizing fasciitis and respiratory tract
      infection in mice using isogenic strains differing only in SpyCEP expression.
      SpyCEP cleaved human CXCL1, 2, 6 and 8 plus murine CXCL1 and 2 at a structurally
      conserved site. Mice were infected in thigh muscle with a strain of S. pyogenes
      that expresses a high level of SpyCEP, or with an isogenic non-SpyCEP expressing
      strain. SpyCEP expression by S. pyogenes hindered bacterial clearance from
      muscle, and enhanced bacterial spread, associated with cleavage of murine
      chemoattractant CXCL1. Mice were then infected with Lactococcus lactis strains
      that differed only in SpyCEP expression. In contrast to the parent L. lactis
      strain (lacks SpyCEP), which was avirulent when administered intramuscularly,
      infection with a strain that expressed SpyCEP heterologously led to dramatic
      systemic illness within 24 h, failure to clear bacteria from muscle and marked
      dissemination to other organs. In the upper airways, SpyCEP expression was
      required for survival of L. lactis but not S. pyogenes. However, dissemination of
      S. pyogenes to the lung was SpyCEP-dependent and was associated with evidence of
      chemokine cleavage. Taken together, the studies provide clear evidence that
      SpyCEP is necessary and sufficient for systemic bacterial dissemination from a
      soft tissue focus in this model and also underlies dissemination in the
      respiratory tract.

PMID- 20158614
TI  - Peripheral motor action of glucagon-like peptide-1 through enteric neuronal
      receptors.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide
      expressed in the enteroendocrine-L cells of small and large intestine and
      released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory
      effects on gastrointestinal motility through vagal afferents and central nervous
      mechanisms; however, no data is available about a direct influence on the
      gastrointestinal wall. Our aim was to investigate the effects of GLP-1 on the
      spontaneous and evoked mechanical activity of mouse duodenum and colon and to
      identify the presence and distribution of GLP-1 receptors (GLP-1R) in the muscle
      coat. METHODS: Organ bath recording technique and immunohistochemistry were used.
      KEY RESULTS: Glucagon-like peptide-1 (up to the concentration of 1 mumol L(-1))
      failed to affect spontaneous mechanical activity. It caused concentration
      dependent reduction of the electrically evoked cholinergic contractions in
      circular smooth muscle of both intestinal segments, without affecting the
      longitudinal muscle responses. Glucagon-like peptide-1 inhibitory effect was
      significantly antagonized by exendin (9-39), an antagonist of GLP-1R. In both
      intestinal preparations, GLP-1 effect was not affected by guanethidine, a blocker
      of adrenergic neurotransmission, but it was significantly reduced by N(omega)
      nitro-l-arginine methyl ester, inhibitor of nitric oxide (NO) synthase. Glucagon
      like peptide-1 failed to affect the contractions evoked by exogenous carbachol.
      Immunohistochemistry demonstrated GLP-1R expression in the enteric neurons.
      Furthermore, 27% of GLP-1R immunoreactive (IR) neurons in the duodenum and 79% of
      GLP-1R-IR neurons in the colon, co-expressed nNOS. CONCLUSIONS & INFERENCES: The
      present results suggest that GLP-1 is able to act in the enteric nervous system
      by decreasing the excitatory cholinergic neurotransmission through presynaptic
      GLP-1Rs, which modulate NO release.

PMID- 20158615
TI  - Cannabinoid 1 receptors modulate intestinal sensory and motor function in rat.
AB  - BACKGROUND: Cannabinoid receptors are involved in visceral pain perception and
      control of intestinal motility in vivo. The underlying mechanisms are not well
      characterized. We aimed to determine whether the cannabinoid-1 (CB(1)) receptor
      modulates intestinal afferent nerve discharge and the peristaltic reflex.
      METHODS: Rats were anesthetized and intestinal segments were removed. Afferent
      nerve discharge from a mesenteric nerve was investigated in vitro in the presence
      of the CB(1) antagonist SR 141716A or the CB(1) agonist WIN 55212-2. The
      myenteric peristaltic reflex was induced by electrical field stimulation and
      influence of SR 141716A or WIN 55212-2 was recorded. KEY RESULTS: Afferent nerve
      discharge to the algesic mediator bradykinin was reduced to 11 +/- 5.1 imp s(-1)
      following pretreatment with SR 141716A and unchanged after WIN 55212-2 compared
      to 63 +/- 15.4 imp s(-1) in controls. At maximum distension pressure (80 cmH(2)O)
      during ramp distension, 92 +/- 12.4 imp s(-1) were reached following SR 141716A
      compared to 260 +/- 13.2 in vehicle controls and 227 +/- 15.4 in WIN 55212-2
      pretreated animals. In contrast, afferent discharge to 5-HT (500 micromol L(-1))
      was increased to 75 +/- 24.6 imp s(-1) following WIN 55212-2 compared to 18 +/-
      5.9 imp s(-1) in controls, whereas SR 141716A had no effect. Ascending neuronal
      contractions were dose-dependently attenuated in the presence of SR 141716A and
      latency of these contractions was reduced. WIN 55212-2 had opposite effects that
      were abolished by SR 141716A. CONCLUSIONS & INFERENCES: Activation of the CB(1)
      receptor differentially alters afferent intestinal nerve sensitivity to
      bradykinin, 5-HT, and noxious mechanical distension, while it strengthens
      ascending neuronal contractions. Further studies are needed to determine the
      physiological relevance of these observations.

PMID- 20158616
TI  - Moving water well: comparing hydraulic efficiency in twigs and trunks of
      coniferous, ring-porous, and diffuse-porous saplings from temperate and tropical
      forests.
AB  - *Coniferous, diffuse-porous and ring-porous trees vary in their xylem anatomy,
      but the functional consequences of these differences are not well understood from
      the scale of the conduit to the individual. *Hydraulic and anatomical
      measurements were made on branches and trunks from 16 species from temperate and
      tropical areas, representing all three wood types. Scaling of stem conductivity
      (K(h)) with stem diameter was used to model the hydraulic conductance of the stem
      network. *Ring-porous trees showed the steepest increase in K(h) with stem size.
      Temperate diffuse-porous trees were at the opposite extreme, and conifers and
      tropical diffuse-porous species were intermediate. Scaling of K(h) was influenced
      by differences in the allometry of conduit diameter (taper) and packing (number
      per wood area) with stem size. *The K(h) trends were mirrored by the modeled stem
      network conductances. Ring-porous species had the greatest network conductance
      and this value increased isometrically with trunk basal area, indicating that
      conductance per unit sapwood was independent of tree size. Conductances were
      lowest and most size-dependent in conifers. The results indicate that differences
      in conduit taper and packing between functional types propagate to the network
      level and have an important influence on metabolic scaling concepts.

PMID- 20158617
TI  - Is social support associated with greater weight loss after bariatric surgery?: a
      systematic review.
AB  - Social support may be associated with increased weight loss after bariatric
      surgery. The objective of this article is to determine impact of post-operative
      support groups and other forms of social support on weight loss after bariatric
      surgery. MEDLINE search (1988-2009) was completed using MeSH terms including
      bariatric procedures and a spectrum of patient factors with potential
      relationship to weight loss outcomes. Of the 934 screened studies, 10 reported on
      social support and weight loss outcomes. Five studies reported on support groups
      and five studies reported on other forms of social support (such as perceived
      family support or number of confidants) and degree of post-operative weight loss
      (total n = 735 patients). All studies found a positive association between post
      operative support groups and weight loss. One study found a positive association
      between marital status (being single) and weight loss, while three studies found
      a non-significant positive trend and one study was inconclusive. Support group
      attendance after bariatric surgery is associated with greater post-operative
      weight loss. Further research is necessary to determine the impact of other forms
      of social support. These factors should be addressed in prospective studies of
      weight loss following bariatric surgery, as they may represent ways to improve
      post-operative outcomes.

PMID- 20158618
TI  - Is atrial fibrillation ablation a futile effort in patients who have markedly
      enlarged left atria?

PMID- 20158619
TI  - Epilepsy or syncope? An analysis of 55 consecutive patients with loss of
      consciousness, convulsions, falls, and no EEG abnormalities.
AB  - BACKGROUND: Patients with loss of consciousness and convulsion often have the
      diagnosis of epilepsy despite normal electroencephalograms (EEGs). OBJECTIVE: To
      evaluate the proportion of patients referred to neurologists with presumed
      epilepsy and normal EEGs who have an alternative cause of syncope. METHODS: It
      was a cross-sectional study of 55 consecutive patients aged 6-85 (41 +/- 24)
      years presenting with faints, falls, convulsions, and normal EEGs, who were
      referred to neurologists before going to cardiologists. All patients underwent
      clinical examination, electrocardiogram, and echocardiogram. Head-up tilt table
      testing (HUT), 24-hour-Holter, and carotid sinus massage was offered as needed.
      Electrophysiological studies were undertaken in patients with structural heart
      disease or severe palpitations. RESULTS: Anticonvulsant agents had been
      prescribed to 35 patients (64%) before entering the study. Vasovagal syncope was
      found in 22 (40%) patients, life-threatening arrhythmias in seven (13%), carotid
      sinus hypersensitivity in six (11%), orthostatic hypotension in three (5%), and
      aortic stenosis in one (2%). Etiology of syncope could not be found in 16 (29%)
      patients. Arrhythmias comprised two complete atrioventricular blocks, one
      sustained monomorphic ventricular tachycardia, one ventricular fibrillation, one
      atrial tachycardia, and two atrioventricular node reentrant tachycardias. Two
      patients developed a prolonged asystole during HUT. Presumptive diagnosis of
      syncope was found in 39 patients (71%). Patients on or off anticonvulsant drugs
      had 64% and 84% diagnosis of syncope, respectively (odds ratio = 0.33; 95%
      confidence interval 0.08-1.36; P = 0.13). CONCLUSIONS: Life-threatening
      arrhythmias and syncope can be present in patients with presumed epilepsy and
      normal EEG. Prescription of anticonvulsant agents in these patients should wait
      for a cardiovascular assessment.

PMID- 20158620
TI  - The effects of caudal or intravenous clonidine on postoperative analgesia
      produced by caudal levobupivacaine in children.
AB  - BACKGROUND: Clonidine is used increasingly in pediatric anesthesia practice to
      prolong the duration of action of caudal block with a local anesthetic agent.
      Which route of administration of clonidine is the most beneficial remains
      unknown. We compared the effects of caudal and intravenous clonidine on
      postoperative analgesia produced by caudal levobupivacaine. METHODS: Sixty ASA I
      and II children, aged 2-8 undergoing inguinal hernia repair or orchidopexy
      surgery received standardized premedication with midazolam and general
      anesthesia. The children were randomized in a double-blind fashion to three
      groups. Group L (n = 20) patients received 0.75 ml x kg(-1) of caudal 0.25%
      levobupivacaine and i.v. 5 ml saline, Group L-Ccau (n = 20) patients received
      0.75 ml x kg(-1) of caudal 0.25% levobupivacaine + 2 microg x kg(-1) clonidine
      and i.v. 5 ml saline, Group L-Civ (n = 20) patients received 0.75 ml x kg(-1) of
      caudal 0.25% levobupivacaine and i.v. 2 microg x kg(-1) clonidine in 5 ml of
      saline. Mean arterial blood pressure, heart rate, peripheral oxygen saturation,
      and end-tidal carbon dioxide values were recorded. Postoperative pain [Children
      and Infants Postoperative Pain Scale (CHIPPS) score], sedation (Ramsay Sedation
      Scale) and motor blockade (Modified Bromage Scale) were assessed at predetermined
      time points during the first 24 h after surgery. RESULTS: Caudal clonidine
      significantly delayed the time to first rescue analgesic and fewer patients
      required rescue analgesia in the 24 h after surgery. No motor block was observed
      in any of the three groups on awakening or during the study period. In Group L
      Ccau, the CHIPPS score was lower than in Group L at all times through 240 min (P
      < 0.05), while the pain scores were lower in Group L-Civ only at extubation and
      at 240 min (P < 0.05). CONCLUSIONS: Caudal clonidine prolongs the duration of
      analgesia produced by caudal levobupivacaine without causing significant side
      effects and this is because of a spinal mode of action.

PMID- 20158621
TI  - Blood pressure changes in migraine patients before, during and after migraine
      attacks.
AB  - Migraine attacks are characterized by headaches associated with neurological,
      gastrointestinal, and autonomic symptoms. A relationship between migraine and
      hypertension or hypotension is controversial. In this study, we aimed to
      determine if blood pressure changes were related to migraine attacks. From the
      outpatient clinic of our neurology department, 62 normotensive migraine patients
      with and without aura were chosen for study in accordance with the International
      Headache Society 2004 criteria. A questionnaire including general and specific
      questions was given to the patients to be filled out during 6 consequent migraine
      attacks. The patients received a fully automatic digital brachial upper arm
      sphygmomanometer (Omron M 4-1) to measure the changes in their blood pressure
      during attacks. The patients were asked to record their blood pressure changes 3
      times: (1) just before or very early, (2) during (when headache peaks), and (3) 1
      hour after the attack. Twenty-three of the 62 patients (57 women, 5 men) had
      migraine with aura (22 women and 1 man), and 39 of them did not have aura (35
      women and 4 men). There was no statistically significant difference between
      systolic and diastolic values obtained before or very early, during the peak
      level, and 1 hour after the end of the attacks (P > 0.05). Although diastolic
      hypotensive values were not different statistically between groups, when all the
      patients were considered, diastolic hypotensive values were detected in a
      considerable number of patients (a total of 115 measurements). In this
      normotensive migrainous population, we observed that diastolic hypotension before
      or very early, during, and after migraine attack was the most significant result
      (5.1%). Although it was not statistically significant, the total number of
      hypotensive values was remarkable.

PMID- 20158622
TI  - Myofascial pain syndrome affecting the quadratus femoris.
AB  - The quadratus femoris is an external rotator of the hip. Quadratus femoris injury
      can accompany damage to the surrounding muscles. Guided by the clinical symptoms,
      the injection technique described here can facilitate accurate diagnosis in
      selected cases.

PMID- 20158623
TI  - Migraine and its relation with lifestyle in women.
AB  - Migraine is a very common primary headache disorder with no underlying
      identifiable pathological cause. It has a profound effect on the well-being and
      general functioning of its victims. Migraine is best understood as a chronic
      disorder with episodic manifestations, progressive in some individuals, having
      dramatic social and economic costs. Migraine causes stress in patients and their
      families, changes the roles and lifestyles and disturbs the social interactions
      between family members. Being more common in women, migraine is a significant
      women's health concern. The low rate of headaches with identifiable organic
      causes suggests that individual and environmental factors are determinants of
      migraine. Therefore, studying lifestyle and its relation with migraine is very
      important. This study examines the relation between migraine headaches and
      lifestyle in women refereed to university clinics in Iran. METHODS: This is a
      case-control study of 170 patients selected randomly using Poisson sampling. The
      study population included female patients suffering from headache referred to the
      neurology clinics and health centers in Iran (with neurologist-diagnosed migraine
      according to the criteria of the International Society of Headache). The study
      population for the control group included women without migraine headache whose
      life conditions were similar to the migraine group and who were living in the
      same area. Data were collected by interview and a questionnaire which was tested
      for reliability and validity using content validity and retest methodologies.
      RESULTS: Findings showed a significant relation between some dimensions of
      lifestyle, such as diet eating habits (P = 0.001), resting and sleeping habits (P
      = 0.012), and drug usage patterns (P = 0.001) with migraine headaches. But there
      were no significant relationships noted between smoking, exercise or stress
      levels with migraine headaches. DISCUSSION: Lifestyle habits, including rest and
      sleep, diet and drug usage, are important factors in migraine attacks. It is
      important to emphasize changing habits, such as improper use of analgesics, to
      decrease side effects in migraine victims. The health centers should consider
      promoting healthy habits and behaviors as a priority in their services.

PMID- 20158624
TI  - Bilateral basal ganglia infarction after mild head trauma.

PMID- 20158625
TI  - Hajdu-Cheney syndrome: infantile onset of hydrocephalus and serpentine fibulae.

PMID- 20158626
TI  - Congenital systemic juvenile xanthogranuloma with placental lesion.

PMID- 20158627
TI  - Acute renal failure caused by fungus balls in renal pelvises.

PMID- 20158628
TI  - Successful bone marrow transplantation in chronic granulomatous disease.

PMID- 20158629
TI  - Diagnostic and therapeutic value of naloxone after intoxication with tramadol in
      a young girl.

PMID- 20158630
TI  - Oral megadose methylphenidate ingestion for suicide attempt.

PMID- 20158631
TI  - Fatal degeneration of specialized cardiac muscle associated with chronic active
      Epstein-Barr virus infection.

PMID- 20158632
TI  - Congenital upper thoracic spondyloptosis with multiple other associated
      anomalies.

PMID- 20158635
TI  - Successful risperidone treatment for behavioral disturbances in Prader-Willi
      syndrome.

PMID- 20158636
TI  - Antenatally diagnosed, intermittently worsened hydronephrosis caused by a
      ureteral polyp.

PMID- 20158637
TI  - Unusual diagnosis of multiple magnet ingestion R1.

PMID- 20158638
TI  - Delayed presentation of Morgagni hernia in a patient with Marfan syndrome.

PMID- 20158639
TI  - Complicated xanthogranulomatous pyelonephritis in a child.

PMID- 20158640
TI  - Norovirus-associated renal acute renal failure with nephrotic syndrome.

PMID- 20158641
TI  - Successful repair in a child with traumatic complex bronchial rupture.

PMID- 20158642
TI  - Application of radiofrequency ablation for giant solid pseudopapillary tumor of
      the pancreas.

PMID- 20158643
TI  - "Typhlitis" in rectum.

PMID- 20158644
TI  - Cytokine profile in a premature infant with systemic Bacillus cereus infection.

PMID- 20158645
TI  - Anesthetic management for a child with unknown type of limb-girdle muscular
      dystrophy.

PMID- 20158646
TI  - Combined amiodarone and low-dose carvedilol treatment for severe heart failure in
      childhood.

PMID- 20158647
TI  - Axillary cellulitis as a manifestation of Kawasaki disease.

PMID- 20158648
TI  - Ulcerative colitis and aortitis syndrome.

PMID- 20158649
TI  - Pneumoperitoneum without intestinal perforation in an adolescent girl.

PMID- 20158650
TI  - Large intracardiac thrombus in a child with refractory nephrotic syndrome.

PMID- 20158651
TI  - Imaging findings in diprosopus tetraophthalmos: a case report.

PMID- 20158652
TI  - Effect of mizoribine in children with inflammatory bowel disease.

PMID- 20158653
TI  - Congenital myotonic dystrophy with cardiac conduction defect and eventration of
      the diaphragm.

PMID- 20158654
TI  - Rare association of malrotation, imperforate anus and Hirschsprung's disease in
      an infant.

PMID- 20158655
TI  - Pulmonary actinomycosis with remote lower chest wall involvement in an
      immunocompetent child.

PMID- 20158656
TI  - Klebsiella oxytoca-positive, penicillin-associated hemorrhagic enterocolitis in
      children.

PMID- 20158657
TI  - Extended-spectrum beta-lactamase-producing bacteria and vesicoureteral reflux in
      children.

PMID- 20158658
TI  - Voriconazole-micafungin combination therapy for acute lymphoblastic leukemia.

PMID- 20158659
TI  - Sporadic neonatal Fanconi's anemia with VACTERL association.

PMID- 20158660
TI  - Scapula as an uncommon site of Langerhans cell histiocytosis in an infant.

PMID- 20158662
TI  - alpha(1)-Antichymotrypsin deficiency associated with liver cirrhosis.

PMID- 20158661
TI  - Novel AGL mutation in a Turkish patient with glycogen storage disease type IIIa.

PMID- 20158663
TI  - Juvenile amyopathic dermatomyositis complicated by progressive interstitial
      pneumonia.

PMID- 20158664
TI  - A rare cause of ascites in a newborn: posterior urethral valve.

PMID- 20158665
TI  - Ictal bradycardia in an infant following surgical treatment for
      hemimegalencephaly.

PMID- 20158666
TI  - Fixed dilated pupils and tacrolimus toxicity in paediatric liver transplant
      patients.
AB  - We report a case series of four children who developed fixed dilated pupils
      associated with high tacrolimus levels (>30 nanograms/millilitre [ng/mL]) in the
      immediate post-operative period following isolated liver or liver and small bowel
      transplantation.

PMID- 20158667
TI  - Long-term monitoring of Epstein-Barr virus DNA load and humoral parameter
      abnormalities in pediatric liver transplant recipients before development of
      malignancy.
AB  - EBV loads and abnormalities of humoral responses were monitored in 51 pediatric
      liver transplant recipients as a proposed non-invasive laboratory tool for early
      detection of changes preceding severe clinical complications. EBV DNA load,
      concentrations of IgM, IgG, IgA, and monoclonal proteins were determined in each
      blood sample. EBV DNA was detected in 70.6% of the children, dysgammaglobulinemia
      of one or more Ig isotype was present in 41.2% of them. MG detected in 43.1% of
      patients correlated with the presence of EBV DNA (p = 0.003) and was usually
      preceded by hypergammaglobulinemia. The median maximum EBV load was significantly
      higher in EBV DNA+/MG+ patients than in EBV DNA+/MG- patients (p = 0.04),
      although there was no correlation between current viral load and appearance of
      MG. Four of 15 EBV DNA-negative patients developed MG, preceded by
      hypergammaglobulinemia in two. Minimization or cessation of immunosuppression in
      42 patients, in whom abnormal biomarkers and/or clinical symptoms raised
      suspicion of disease progression, permitted complete resolution of abnormalities
      in all but one patient who developed B-NHL and died. Simultaneous monitoring of
      protein profiles and EBV DNA load together with thorough physical evaluation of
      children after LTx is important for early implementation of suitable preemptive
      therapy.

PMID- 20158668
TI  - A photochemical study of diclofenac and its major transformation products.
AB  - The photolytic transformation of 2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid
      (diclofenac) and its transformation products (TPs) (8-chloro-9H-carbazol-1-yl)
      acetic acid (Cz1), 2-(2-chloro-phenylamino)-benzaldehyde (Ald) and (1,4-dioxo-4,9
      dihydro-1H-carbazol-8-yl) acetic acid (Cz4) in aqueous solutions have been
      studied. The previously unreported TP (Cz4) was isolated by LC and completely
      characterized by NMR and MS. UV-absorption spectra of diclofenac and three of its
      TPs were determined and used to calculate disappearance quantum yields. The
      dominating transformation pathway of diclofenac occurs via initial formation of
      Cz1 and proceeds to form mainly (Cz4) over 200 min of UV-irradiation. A second
      minor transformation pathway, which yields Ald as the sole product, was observed
      only under deaerated conditions.

PMID- 20158669
TI  - Photophysics of zinc (II) phthalocyanine polymer and gel formulation.
AB  - The photophysical properties of lipophilic phthalocyanines encapsulated into a
      polymer and two different gels were studied in order to predict their
      photosensitizing efficacy in vivo. Photophysical techniques for solid phase were
      adapted for light dispersing samples. Gel formulation of two tetrasubstituted
      phthalocyanines, tetra-t-butylphthalocyaninato zinc(II) (1), tetrakis(1,1
      dimethyl-2-phthalimido)ethylphtalocyaninatozinc(II) (2) and two octasubstituted
      phthalocyanines, 2,3,9,10,16,17,23,24-octakis(decyloxy)phthalocyaninatozinc(II)
      (3) and 2,3,9,10,16,17,23,24-octakis[(N,N
      dimethylamino)ethylsulfanyl]phthalocyaninatozinc(II) (4) were investigated for
      their possible use in photodynamic therapy for topical purposes. Supporting the
      fact that gel formulation improves the photophysical properties of
      phthalocyanines, singlet molecular oxygen quantum yield (Phi(Delta)) values for 1
      4 zinc(II) phthalocyaninates in Lutrol F 127-Cremophor RH 40 were 0.60, 0.60,
      0.20 and 0.26, respectively. Permeation studies showed that no release of
      phthalocyanines occurs, thus indicating there should be no risk of generalized
      skin photosensitivity in areas other than the dye-deposition site.

PMID- 20158670
TI  - Optical properties of fluorescein-labeled organoclay.
AB  - We report the preparation of aminopropyl-functionalized magnesium phyllosilicate
      (Mg-organoclay) conjugated to fluorescein isothiocyanate (FITC) functionality
      (FITC-organoclay) by one-pot sol-gel synthesis. The physical characteristics of
      the Mg- and FITC-organoclays were examined by scanning electron microscopy (SEM),
      X-ray diffraction (XRD), FT-IR and UV-Vis spectrophotometry. X-ray fluorescence
      and elemental analysis were conducted to confirm the composition of the Mg
      organoclay. The FITC-organoclay particles were polydispersed with an average
      particle size of approximately 50 nm, as determined from SEM images. The XRD
      patterns of FITC-organoclay exhibited broad peaks and reduced basal d(001)
      indicating a less condensed and more disordered structure than was observed for
      Mg-organoclay. The conjugation between FITC- and Mg-organoclay was characterized
      by FT-IR spectroscopy. Fluorescence excitation and emission spectral data
      demonstrated the successful conjugation of FITC dye molecules to the Mg
      organoclay. The time-resolved fluorescence measurements revealed that FITC had a
      lifetime of 4.58 ns, whereas the lifetime of FITC-organoclay required a double
      exponential fit (tau(1,2) = 0.72 and 2.68 ns). As a result, the lifetime of the
      FITC-organoclay was shorter than that of FITC in ethanol and indicated moderate
      photostability in the solution state. The cellular uptake of FITC-organoclay in
      human lung alveolar carcinoma epithelial cells (A549) was quantified and
      characterized.

PMID- 20158671
TI  - Temperature and solar radiation interactions on 3H-leucine incorporation by
      bacterioplankton in a subtropical estuary.
AB  - Although the effects of UV radiation are thought to be temperature independent,
      the photoinhibition of aquatic bacteria may be temperature dependent owing to
      enzymatic repair kinetics, an important consideration for climate change
      analyses. We examined the interactions between temperature and solar radiation in
      water samples collected from the Blackwater River, Pensacola Bay, and the coastal
      Gulf of Mexico (Florida) in July 2008. Subsamples were incubated in the dark for
      20 h at either the in situ temperature, +5 degrees C from in situ or -5 degrees C
      from in situ after which they were amended with (3)H-leucine and irradiated in
      full sunlight at their respective temperatures and compared to samples incubated
      simultaneously in the dark. Temperature and light significantly affected (3)H
      leucine incorporation at all locations and interactive effects between
      temperature and sunlight were found for Pensacola Bay and the Gulf. Generally,
      warmer waters reduced photoinhibition. The -5 degrees C treatment was always
      significantly more inhibited than the +5 degrees C treatment, but the in situ
      temperature and +5 degrees C and -5 degrees C treatments were not always
      significantly different. Photoinhibition reduction at warmer temperatures
      suggests specific effects on photobiology not observed in general cellular
      activity may be important in determining interactive ecosystem effects of climate
      change.

PMID- 20158672
TI  - Seasonal impacts of solar UV radiation on photosynthesis of phytoplankton
      assemblages in the coastal waters of the South China Sea.
AB  - We carried out experiments to evaluate seasonal changes in the impacts of UV
      radiation (UVR, 280-400 nm) on photosynthetic carbon fixation of phytoplankton
      assemblages. Surface water samples were obtained in the coastal area of the South
      China Sea, where chlorophyll a ranged 0.72-3.82 microg L(-1). Assimilation
      numbers (photosynthetic carbon fixation rate per chl a) were significantly higher
      during summer 2005 than those in spring and winter 2004. The mean values obtained
      under photosynthetically active radiation (PAR) were 2.83 (spring 2004), 4.35
      (winter 2004) and 7.29 microg C (microg chl a)(-1) h(-1) (summer 2005),
      respectively. The assimilation numbers under PAR + UVR were 1.58, 2.71 and 5.28
      microg C (microg chl a)(-1) h(-1), for spring, winter and summer, respectively.
      UVR induced less inhibition of photosynthesis during summer 2005 than during the
      other seasons, in spite of the higher UVR during summer. The seasonal differences
      in the productivity and photosynthetic response to UV were mainly due to changes
      in water temperature, while irradiance and vertical mixing explained >80% of the
      observed variability. Our data suggest that previous studies in the SCS using UV
      opaque vessels might have overestimated the phytoplankton production by about 80%
      in spring, 61% in winter and 38% in summer.

PMID- 20158673
TI  - Erythemal ultraviolet exposure of cyclists in Valencia, Spain.
AB  - UV exposure is considered to be one of the most important risk factors in skin
      cancers, mainly in outdoor occupational or recreational activities. Outdoor
      athletes such as cyclists receive regular and significant solar UV erythemal
      radiation (UVER). The aim of this work was to quantify UVER exposure of amateur
      cyclists over the course of several days in their training schedules. To quantify
      UVER exposure of this group, dosimeters (Viospor) were attached at the top of the
      helmet in the course of their training. The study took place in Valencia, Spain,
      in June to July 2008 and February to March 2009, and involved a group of five
      cyclists over a period of 4 days for each period. The mean 2-day personal UV
      exposure was 32.24 +/- 4.14 SED (standard erythema dose) in summer and 11.30 +/-
      5.36 SED in the winter period. One SED is defined as an effective radiant
      exposure of 100 J m(-2) when weighted with the International Commission on
      Illumination (CIE) erythemal response function. The mean exposure ratio (ER) of
      cyclists was 0.37 +/- 0.04 in summer and 0.40 +/- 0.11 in winter. The cyclists
      received the highest UVER exposure in the summer period, but in both training
      periods UVER exposure was in excess of occupational and recreational guidelines,
      indicating that protective measures are very necessary.

PMID- 20158674
TI  - The envelope damage of Tetrahymena in the presence of TiO2 combined with UV
      light.
AB  - The biological consequences of exposure to TiO(2), UV light and their combined
      effects were studied on the cellular envelopes of Tetrahymena. For Tetrahymena
      cells treated with TiO(2) or UV light alone, the cell membrane shrunk while still
      maintaining the original elliptoid shape. Cells treated by TiO(2) under UV light
      irradiation experienced the most serious damage by peroxidation. A pear-shaped
      cell was formed due to serious shrinkage and cilia loss. An increase in the
      fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene was observed,
      indicating a significant decrease in membrane fluidity. Quantum dot (QD) labeling
      revealed that damaged cells could not function properly or absorb extracellular
      materials selectively. QDs were able to enter the damaged cells or be absorbed on
      the cell surface. Attenuated total reflection Fourier transform infrared spectra
      revealed that amide groups and PO(2)(-) of the phospholipid phospho-diester, both
      in the hydrophobic end exposed to the outer layer, were the easiest to be
      oxidized. Other groups like CH(2) and CH(3) were also involved, but showed a
      resistance to photocatalytic peroxidation. The differences can be attributed to
      the bond energy as well as the ordering and position of the groups.

PMID- 20158675
TI  - Retraction. The relationship between physical activity and health-related quality
      of life: a systematic review of current evidence.

PMID- 20158676
TI  - The impact of task controllability on perceived control and cardiovascular
      processes.
AB  - This article examines the impact of task control on perceived control and
      cardiovascular processes. Fifty-eight undergraduates performed a computer task
      where the functionality of the computer mouse was used to manipulate task
      control. Results are consistent with the proposition that actual control triggers
      an initial physiological response which can be modified temporally later by
      perceived control and that male participants react psychologically faster to
      changes in task control than female participants.

PMID- 20158677
TI  - Looking at emotional words is not the same as reading emotional words: Behavioral
      and neural correlates.
AB  - Recent research suggests that the allocation of attentional resources to
      emotional content during word processing might be sensitive to task requirements.
      This question was investigated in two tasks with similar instructions. The
      stimuli were positive, negative, and neutral nouns. Participants had to identify
      meaningful words embedded in a stream of non-recognizable stimuli (task 1) or
      pseudowords (task 2). Task 1 could be successfully performed on the basis of the
      perceptual features whereas a lexico-semantic analysis was required in task 2.
      Effects were found only in task 2. Positive nouns were identified faster, with
      fewer errors and elicited larger amplitude in an early negativity. Also, the
      amplitude of a late positivity was larger for both positive and negative nouns
      than for neutral nouns. It is concluded that some degree of linguistic processing
      is needed to direct attention to the affective content during word processing.

PMID- 20158678
TI  - Fronto-striato-limbic hyperactivation in obsessive-compulsive disorder during
      individually tailored symptom provocation.
AB  - Anxiety disorders have been linked to a hyperactivated cortico-amygdalar
      circuitry, but the amygdala's role in the pathophysiology of obsessive-compulsive
      disorder (OCD) remains unclear. This fMRI study examined the cortico-limbic
      correlates of individually tailored symptom provocation in 14 unmedicated OCD
      patients and 14 controls. In addition to OCD-relevant pictures, aversive and
      neutral control stimuli were included. Patients showed increased fronto-striatal
      activation to OCD-relevant stimuli contrasted with both control categories.
      Briefly presented symptom-related triggers elicited stronger amygdala engagement
      in patients than in controls. This effect, however, did also occur to aversive
      stimuli and was not symptom specific. Augmented amygdala involvement in patients
      reflects general emotional hyperarousal. Symptom-specific frontal activation
      points towards a sustained endeavor to suppress exaggerated emotional responses
      to OCD triggers.

PMID- 20158679
TI  - Nomenclature for factors of the HLA system, update December 2009.

PMID- 20158681
TI  - Convalescent transfusion for pandemic influenza: preparing blood banks for a new
      plasma product?
AB  - Due to the potential of a severe pandemic to limit efficacy or availability of
      medical countermeasures, some researchers have begun a search for new
      interventions that could complement the planned antiviral- and vaccine-based
      response to an influenza pandemic. One such countermeasure-the transfusion of
      pandemic influenza-specific antibodies from surviving patients to the clinically
      ill-is the focus of this commentary. Passive immunotherapy, which includes the
      use of monoclonal antibodies (MoAbs), hyperimmune globulin, or convalescent
      plasma, had been used before the advent of antibiotics and has recently reentered
      the limelight due to the accelerating development of MoAb therapies against
      cancer, a number of microbes, allograft rejection, and a host of other
      conditions. After the plausible biologic mechanism and somewhat limited data
      supporting the efficacy for this modality against influenza are reviewed, safety
      and logistical concerns for utilization of this potential new product (fresh
      convalescent plasma against influenza [FCP-Flu]) are discussed. FCP-Flu could
      indeed prove useful in a response to a pandemic, but two necessary items must
      first be satisfied. Most importantly, more research should be conducted to
      establish FCP-Flu efficacy against the current and other pandemic strains.
      Second, and also importantly, blood banks and donor centers should examine
      whether offering this new product would be feasible in a pandemic and begin
      planning before a more severe pandemic forces us to respond without adequate
      preparation.

PMID- 20158682
TI  - Identification of specificities of antibodies against human leukocyte antigens in
      blood donors.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of
      transfusion-related mortality. Blood centers are implementing TRALI risk
      reduction strategies based on screening apheresis donors for antibodies to human
      leukocyte antigens (HLA). STUDY DESIGN AND METHODS: HLA antibody screening was
      performed on 7920 blood donors from the Leukocyte Antibody Prevalence Study
      (LAPS) using Luminex-based normalized background (NBG) cutoff ratios of 10.8
      (Class I) and 6.9 (Class II). Single antigen bead (SAB) assay cutoffs of 2500
      median fluorescence intensity units (Class I) and 1500 (Class II) were
      established based on results of two subpopulations of LAPS donors. Antibody
      frequencies against HLA A, B, C, DR, DQ, and DP antigens were determined for
      screen-reactive donors with prior pregnancies. RESULTS: SAB reactivity for
      samples above our multiantigen bead NBG cutoffs was 78% for Class I and 79% for
      Class II. The SAB-positive rate increased among women with zero to four or more
      pregnancies (0.3%-15.6% Class I and 0.4%-18% Class II; p < 0.00001). The highest
      frequency antibodies were DR11 and B15 (4.4% of women with prior pregnancies).
      The majority of Class I positives contained more than five specificities. For
      Class II, antibody-positive women segregated into two groups: a single
      specificity or more than five specificities. CONCLUSIONS: Identification of HLA
      antigen specificities supports pregnancy associations previously found with
      screening assays. The significance of particular HLA specificities for inducing
      TRALI is currently being evaluated in a large lookback study of recipients of
      high-plasma-volume components from this donor cohort.

PMID- 20158683
TI  - Screening of Canadian Blood Services donors for severe immunoglobulin A
      deficiency.
AB  - BACKGROUND: Immunoglobulin A (IgA)-deficient patients with antibodies to IgA
      require transfusions with IgA-deficient blood components to either avoid or
      reduce the frequency of serious adverse reactions. To supply compatible blood
      components for these individuals, the Canadian Blood Services (CBS) National
      Testing Laboratory must initially screen and subsequently identify, after
      confirmatory testing at the American Red Cross (ARC), donors severely deficient
      in IgA (<0.05 mg/dL). STUDY DESIGN AND METHODS: The Ouchterlony double
      immunodiffusion assay was used as an initial screen at CBS to identify IgA
      deficient donors (test sensitivity 2-4 mg/dL). Sample aliquots from these donors
      were then sent to the ARC for confirmatory testing using an enzyme-linked
      immunosorbent assay method for severe IgA deficiency (<0.05 mg/dL) and a passive
      hemagglutination assay to detect anti-IgA. RESULTS: From November 2007 to
      December 2008, of 54,594 samples screened initially at CBS there were 137 samples
      (0.251%) identified as possibly IgA deficient. Of these 137, there were 100
      reports returned from ARC confirming severe IgA deficiency in 65 donors (25
      female, 40 male) without detectable anti-IgA and in 35 donors (18 female, 17
      male) with anti-IgA. The remaining 37 donors had IgA levels of more than 0.05
      mg/dL. CONCLUSION: Results from the ARC confirmed a frequency of 1 in 546 in the
      CBS' blood donor population for severe IgA deficiency (<0.05 mg/dL), 1 in 840 for
      those without anti-IgA, and 1 in 1560 for those with antibody. Donors repeatedly
      confirmed as severely IgA deficient without anti-IgA were considered eligible for
      the CBS IgA-deficient donor registry program.

PMID- 20158684
TI  - The status of massive transfusion protocols in United States trauma centers:
      massive transfusion or massive confusion?
AB  - BACKGROUND: Massive transfusion protocol (MTP) utilization and makeup is unknown.
      STUDY DESIGN AND METHODS: A Web-based survey was sent to members of the Eastern
      Association for the Surgery of Trauma and published in the American Association
      for the Surgery of Trauma newsletter. Comparisons were made with chi-square and
      logistic regression. RESULTS: A total of 186 surgeons and 59 center directors
      responded. To avoid bias, directors' responses are reported. Sixty percent
      annually admit more than 1500 patients. Sixty-seven percent had in-house
      attending coverage and 85% had a MTP. Presence of a MTP was not predicted by
      institution size, level, residency status, or admissions. Sixty-five percent of
      MTPs had been in place less than 5 years with 18% less than 1 year. Designs
      varied: 23% had one batch of components, 25% had two or three, 41% had more than
      three, and 11% did not use batches. Only 62% of first batches contained fresh
      frozen plasma (FFP). In the second batch 98% had FFP. All third boxes had FFP. A
      ratio of FFP : red blood cells (RBCs) of less than 1 in the first batch predicted
      a ratio less than 1 in the second batch (p = 0.013). Twenty-seven percent had
      blood stored in the emergency department and 14% in the operating room. Twenty
      four percent of MTPs autoactivate and 80% are trauma surgeon activated, 66% by
      the anesthesia staff, 32% by other surgeons, and 17% by the blood bank. Trauma
      surgeons activate the MTP most. CONCLUSION: Most centers have a MTP. Protocols
      are variable and new, and half have a 1:1 FFP : RBC ratio. Protocols with fewer
      initial units of FFP compared to RBCs maintain this.

PMID- 20158685
TI  - Effects of red blood cells on hemostasis.
AB  - BACKGROUND: Currently there is no sensitive laboratory test to establish the
      influence of red blood cells (RBCs) on hemostasis. As thromboelastography (TEG)
      measures hemostasis in whole blood, taking into account the interactions of all
      cellular elements, we used this instrument to investigate the role that RBCs play
      in hemostasis. STUDY DESIGN AND METHODS: In 29 patients with chemotherapy-induced
      anemia we studied the effect of progressive anemia on the coagulation profile. In
      24 patients with chronic anemia we studied the effect of transfusion of RBCs on
      coagulation. Finally, in 18 patients we evaluated whether storage time of RBCs
      has additional effects on hemostasis. RESULTS: We observed a significant negative
      correlation between hemoglobin and TEG variables related to both clot strength
      and elasticity (p < 0.05). Moreover, anemia was associated with a delay in the
      initiation of the coagulation cascade. Correction of anemia by RBC transfusion
      resulted in significant shortening of this initiation phase with now the opposite
      effect on clot strength and elasticity. The negative effects on clot quality were
      significantly worse when fresh RBCs were transfused compared to longer-stored
      RBCs. Furthermore, in contrast to the longer-stored RBCs, fresh RBCs did not
      enhance initial fibrin formation. CONCLUSIONS: In this study we found that anemia
      was associated with a delay in the initiation of the coagulation cascade with a
      finally formed clot with superior strength and viscoelastic properties.
      Transfusion of RBCs was associated with impaired clot quality, with even worse
      effects on the initial fibrin build-up and clot quality by fresh RBCs.

PMID- 20158686
TI  - Differential profiling of human red blood cells during storage for 52 selected
      microRNAs.
AB  - BACKGROUND: MicroRNAs (miRNAs), the negative regulators of cellular mRNAs, are
      present in mature red blood cells (RBCs) in abundance relative to other blood
      cells. So far, there are no studies aimed at identifying large-scale miRNA
      profiles during storage of RBCs. STUDY DESIGN AND METHODS: RNA samples from each
      RBC bag stored at 4 degrees C were collected on Days 0, 20, and 40 and subjected
      to miRNA profiling by using a membrane-based array. Fifty-two selected miRNAs of
      cellular apoptotic pathway represent the array. Through bioinformatics analyses,
      we identified potential target genes for selected miRNAs. RESULTS: Differential
      profiling of RBCs for 52 miRNAs revealed two distinguishable patterns during
      storage: Forty-eight miRNAs demonstrated no trend at all, while four miRNAs, miR
      96, miR-150, miR-196a, and miR-197, demonstrated an increase up to Day 20 and
      subsequently decreased during storage. We selected miR-96 and subjected it to
      standard bioinformatics analyses for target gene predictions, which identified
      several mRNAs including the RBC proapoptotic calpain small subunit-1 (CAPNS1) as
      potential targets of miR-96. To validate these predictions, we selected CAPNS1
      mRNA as an example and confirmed its presence in the RBCs. Future experimental
      verification would help define miR-96-CAPNS1 interaction, if any, in the stored
      RBCs. CONCLUSIONS: This study for the first time provided a differential profile
      of stored RBCs for selected miRNAs related to cellular apoptotic pathway and
      opened new avenues toward identification of novel in vitro RBC biomarkers of
      storage lesions. Future studies focusing on target gene-miRNA interactions in
      stored RBCs would also unravel underlying mechanisms of storage lesions.

PMID- 20158687
TI  - Lipidomic analysis of platelet senescence.
AB  - BACKGROUND: A hallmark of platelet (PLT) storage lesion is the loss of PLT
      lipids. Due to technical limitations a detailed lipidomic analysis of
      plateletpheresis products during storage was so far not available. STUDY DESIGN
      AND METHODS: Fifty plateletpheresis products were stored for 5 days at 22 degrees
      C under agitation. Each day plasma and PLTs were isolated by gel filtration and
      lipid species analyzed by electrospray ionization tandem mass spectrometry.
      RESULTS: During 5 days of storage the total lipid content decreased by 10% in
      PLTs and increased by 5% in plasma. We observed the following changes in lipid
      class fractions during storage relative to the day of preparation: increases of
      69% ceramide (Cer), 32% lysophosphatidylcholine (LPC), and 49% cholesteryl esters
      (CE) and a decrease of 10% free cholesterol (FC) in PLTs and elevation of 43% LPC
      and 14% CE and a decline of 20% phosphatidylcholine (PC) and 24% FC in plasma.
      Significant lipid species shifts were observed for phosphatidylserine, Cer, and
      LPC. Correlation analysis of lipid changes in plasma indicated that lecithin
      cholesterol-acyltransferase (LCAT) activity may be responsible for the shift in
      plasma lipid composition. These lipid changes correlated between plasma and PLTs
      for LPC, FC, and CE fractions. CONCLUSIONS: This study presents for the first
      time detailed lipid species profiles of PLTs and plasma during storage of PLT
      concentrates. These data provide clear evidence for LCAT-mediated esterification
      of FC and LPC generation in the plasma of PLT concentrates. Moreover, we showed
      evidence that these changes also impact PLT lipid composition.

PMID- 20158688
TI  - Supernates from stored red blood cells inhibit platelet aggregation.
AB  - BACKGROUND: Previously, we reported that red blood cells (RBCs) stored in AS-5
      accumulated proinflammatory substances during storage. We observed in those
      studies that supernates from nonleukoreduced (NLR) RBCs reduced mean anti-CD41a
      fluorescein isothiocyanate (FITC) fluorescence on platelets (PLTs), indicative of
      decreased expression of glycoprotein (GP)IIb/IIIa on the PLT membrane. The
      objective of this study was to determine if supernates from stored RBCs impaired
      PLT aggregation as a consequence of reduction in GPIIb/IIIa expression. STUDY
      DESIGN AND METHODS: Leukoreduced (LR) and NLR RBC units were prepared in AS-5 and
      stored at 1 to 6 degrees C for 6 weeks. Supernates from RBC samples collected
      every 2 weeks were mixed with freshly collected type-matched blood and incubated
      for 30 minutes at 37 degrees C. PLTs in each incubated blood sample were
      evaluated for GPIIb/IIIa expression by flow cytometry and for aggregation
      response to collagen by whole blood aggregometry. RESULTS: Supernates from stored
      NLR RBCs reduced CD41a-FITC fluorescence on PLTs by 15% to 31%. A reduction in
      fluorescence was induced by supernates of RBCs stored for 14 days and increased
      as storage time increased. Supernates from Day 42 NLR RBCs reduced the mean
      amplitude of PLT aggregation by 31% compared to Day 0 supernates and lengthened
      the time before onset of aggregation by 21%. In addition, amplitude correlated
      directly and lag time correlated inversely with CD41a-FITC fluorescence in all
      samples. Supernates from prestorage LR RBCs did not affect PLT CD41a-FITC
      fluorescence or aggregation response. CONCLUSIONS: Substances that decrease
      expression of GPIIb/IIIa and inhibit PLT aggregation accumulate in NLR RBCs.
      Accumulation of this material is prevented by leukoreduction.

PMID- 20158689
TI  - Parvovirus B19 infection transmitted by transfusion of red blood cells confirmed
      by molecular analysis of linked donor and recipient samples.
AB  - BACKGROUND: Extremely high viremic levels of parvovirus B19 (B19V) can be found
      in acutely infected, but asymptomatic donors. However, reports of transmission by
      single-donor blood components are rare. In this prospective study, paired donor
      recipient samples were used to investigate the transfusion risk. STUDY DESIGN AND
      METHODS: Posttransfusion plasma or blood samples from recipients were tested for
      B19V DNA by polymerase chain reaction, generally at 4 and 8 weeks, and for anti
      B19V immunoglobulin (Ig)G by enzyme immunoassay, at 12 and 24 weeks. To rule out
      infection unrelated to transfusion, pretransfusion samples and linked donor's
      samples for each B19V DNA-positive recipient were assayed for B19V DNA and anti
      B19V IgG and IgM. To confirm transmission, sequencing and phylogenetic analysis
      were performed. RESULTS: A total of 14 of 869 (1.6%) recipients were B19V DNA
      positive, but only 1 of 869 (0.12%; 95% confidence interval, 0.0029%-0.6409%) was
      negative for B19V DNA and anti-B19V IgG before transfusion and seroconverted
      posttransfusion. This newly infected patient received 5 * 10(10) IU B19V DNA in
      one red blood cell (RBC) unit from an acutely infected anti-B19V-negative donor
      in addition to RBCs from three other donors that cumulatively contained 1320 IU
      of anti-B19V IgG. DNA sequencing and phylogenetic analysis showed that sequences
      from the linked donor and recipient were identical (Genotype 1), thus
      establishing transfusion transmission. CONCLUSIONS: The 0.12% transmission rate
      documented here, although low, could nonetheless result in hundreds or thousands
      of infections annually in the United States based on calculated confidence
      limits. Although most would be asymptomatic, some could have severe clinical
      outcomes, especially in neonates and those with immunocompromised or hemolytic
      states.

PMID- 20158690
TI  - Duration of red blood cell storage and survival of transfused patients (CME).
AB  - BACKGROUND: Disquieting reports of increased complication and death rates after
      transfusions of red blood cells (RBCs) stored for more than 14 days prompted us
      to perform an observational retrospective cohort study of mortality in relation
      to storage time. STUDY DESIGN AND METHODS: We conducted a cohort study utilizing
      data on all recipients of at least one RBC transfusion in Sweden and Denmark
      between 1995 and 2002, as recorded in the Scandinavian Donations and Transfusions
      (SCANDAT) database. Relative risks of death in relation to storage time were
      estimated using Cox regression, adjusted for several possible confounding
      factors. RESULTS: After various exclusions, 404,959 transfusion episodes remained
      for analysis. The 7-day risk of death was similar in all exposure groups, but a
      tendency for a higher risk emerged among recipients of blood stored for 30 to 42
      days (hazard ratio, 1.05; 95% confidence interval [CI], 0.97-1.12), compared to
      recipients of blood stored for 10 to 19 days. With 2-year follow-up, this excess
      remained at the same level (hazard ratio, 1.05; 95% CI, 1.02-1.08). No dose
      response pattern was revealed and no differential effect was seen when the
      analyses were restricted to recipients of leukoreduced units only. CONCLUSION:
      Although a small excess mortality was noted in recipients of the oldest RBCs, the
      risk pattern was more consistent with weak confounding than with an effect of the
      momentary exposure to stored RBCs. It seems, thus, that any excess mortality
      conferred by older RBCs in the combined Swedish and Danish transfusion recipient
      population is likely less than 5%, which is considerably smaller than in the
      hitherto largest investigation.

PMID- 20158691
TI  - Treatment of osteoporosis after liver transplantation with ibandronate.
AB  - Osteoporosis is a major side-effect after liver transplantation (LTX). Therefore,
      the objective of the study was to evaluate the efficacy of ibandronate to reduce
      fractures after LTX. Seventy-four patients after LTX were included in the study
      and measurements of bone mineral density (BMD) of lumbar spine and proximal femur
      using dual energy X-ray absorptiometry (DEXA) were performed prior to and 3, 6,
      12 and 24 months after surgery. The study group (IBA) consisted of 34 patients
      who received calcium (1 g/day), vitamin D3 (800-1000 IE/day) and ibandronate 2 mg
      every 3 months intravenously for 1 year. The control group consisted of 40
      patients (CON) who received calcium and vitamin D3 at the same dosages.
      Prevalence of new fractures was predefined as primary endpoint. Changes of BMD
      and biochemical markers of bone metabolism were also investigated. In all
      patients, we found a reduction of BMD in the first few months after LTX. In the
      lumbar spine and the proximal femur the maximum reduction occurred 3 and 6 months
      post-LTX. One and 2 years after transplantation, the group receiving ibandronate
      demonstrated a better recovery from loss of BMD and a significantly lower
      prevalence of fractures (IBA 2 vs. CON 10 P < 0.04, chi(2)). Ibandronate with
      calcium and vitamin D3 reduces the BMD-loss after LTX and decreases the rate of
      bone fractures significantly.

PMID- 20158692
TI  - Noninvasive evaluation of renal allograft fibrosis by transient elastography--a
      pilot study.
AB  - Chronic allograft injury (CAI) is the most common cause of graft failure after
      the first year of transplantation. To date, only protocol biopsies can reveal
      subclinical disease. Transient elastography (TE) is a novel noninvasive technique
      that has demonstrated high reliability in the assessment of liver fibrosis. This
      study evaluates the feasibility of TE for the assessment of renal allograft
      fibrosis. Fifty-seven patients underwent TE by the FibroScan device. Biopsies
      were performed in 20 patients. Measurement of parenchymal stiffness by TE was
      successful in 55 of 57 patients (96.5%). Stiffness was significantly correlated
      to the extent of interstitial fibrosis (Pearson r: 0.67, P: 0.002, R(2): 0.45)
      and inversely related to estimated glomerular filtration rate (eGFR) (Pearson r: 
      0.47, P: 0.0003, R(2): 0.22). Stiffness values of patients with an eGFR >50
      ml/min were significantly lower than in patients with an eGFR < or = 50 ml/min
      (22.2 +/- 11.0 vs. 37.1 +/- 14.2 kPa, P: 0.0005). The stiffness values of CAI
      Banff grades 0-1 differed significantly from grade 2 (P: 0.008) and grade 3 (P:
      0.046). Parenchymal stiffness measured by TE reflects interstitial fibrosis in
      kidney allografts. A longitudinal assessment of parenchymal stiffness might be a
      powerful tool to identify patients with CAI who benefit from biopsy and
      consequent adaptation of the immunosuppressive regime.

PMID- 20158693
TI  - Depression and disease severity as correlates of everyday physical activity in
      heart transplant candidates.
AB  - It is unclear to what extent patients awaiting heart transplantation (HTx) engage
      in physical activities. We examined the everyday physical activity and its
      associations with depressive symptoms and disease severity in 318 patients newly
      registered for HTx in the multi-site study 'Waiting for a New Heart' (aged 53.5
      +/- 11.4 years, 18% female patients). Participants completed questionnaires
      assessing depressive symptomatology and physical activity (number of physical
      activities, caloric expenditure associated with each activity), and estimated the
      distance they were able to walk without a break. Medical parameters at the time
      of listing [e.g. peak oxygen consumption (peakVO(2)); the German Transplant
      Society Score (GTSS)] were provided by Eurotransplant. Almost 50% of patients
      engaged in activities of daily living (housework, walking), but <10% engaged in
      regular exercise. All physical activity measures correlated significantly with
      peakVO(2) (Ps < 0.01). Elevated depression scores were present in 39% of
      patients. Controlling for confounding variables (e.g. peakVO(2), diastolic blood
      pressure, GTSS, age), depressive symptomatology accounted for additional variance
      in all physical activity measures (Ps < 0.05). The association of depressive
      symptoms with reduced physical activity suggests two important perspectives:
      attempts to increase physical activity (especially in the area of daily living)
      might benefit from targeting depression, and increased physical activity might
      also help to reduce depressive symptoms.

PMID- 20158694
TI  - Assessment of brain death of organ donors in Iran.

PMID- 20158695
TI  - Pediatric living-donor liver transplantation for acute liver failure: analysis of
      57 cases.
AB  - We reviewed 57 pediatric patients admitted with acute liver failure to Kyoto
      University Hospital in Japan over a period of 15 years to compare the etiology
      and the long-term outcome of infants and children after living donor liver
      transplantation (LDLT). Patients were divided into two groups according to age at
      the time of liver transplantation, infants group (<1 year, n = 20), and children
      group (1-18 years, n = 37). The overall survival rates were 73.6%, 69.5% and
      67.2% at 1, 5, and 10 years after LDLT respectively. Age of recipients at the
      time of LDLT had a strong impact on their outcome, Children had significantly
      better outcome than infants (P = 0.001). Surgical complications were comparable
      between both groups. Infants had higher rates of acute cellular rejection (ACR),
      which was associated with features of hepatitis in many cases. Refractory ACR was
      the leading cause of death in eight out of 12 infants, while it resulted in loss
      of one child only. Cox's proportional hazard regression model was used to examine
      potential risk factors for graft loss and it shows that age <1 year was
      associated with high risk of graft loss [hazard ratio (HR) = 11.393; CI = 1.961
      76.1763] (P < 0.05). In conclusion, Infants had poorer prognosis than children
      and refractory ACR was the leading cause of death. Using additional
      immunosuppressant for cases with severe and atypical rejections is recommended.

PMID- 20158696
TI  - Stimulation of human neutrophils with sera containing HLA Class I alloantibody
      causes preferential degranulation of azurophilic granules and secretory vesicles.
AB  - BACKGROUND AND OBJECTIVES: The activation of neutrophils by human leukocyte
      antigen (HLA) Class I alloantibody is thought to be involved in transfusion
      related acute lung injury. Neutrophils contain various biological substances in
      four groups of granules, including secretory vesicles, azurophilic granules,
      specific granules and gelatinase granules. To characterize the activation of
      neutrophils by HLA Class I alloantibody, we investigated whether HLA Class I
      alloantibody could cause the degranulation of these groups of granules either
      coordinately or selectively. MATERIALS AND METHODS: Sera containing HLA-A24
      alloantibody were incubated with neutrophils in a washed whole blood system.
      CD11b expression (secretory vesicles) on neutrophils was analysed by flow
      cytometry, and the secretion of markers of each granule was determined by ELISA.
      RESULTS: The treatment of cross-matching-positive neutrophils with sera
      containing HLA-A24 alloantibody caused the significant expression of CD11b, and
      the significant secretion of neutrophil elastase and myeloperoxidase, azurophilic
      granule markers and heparin-binding protein (HBP), which is localized in
      secretory vesicles and azurophilic granules when compared with cross-matching
      negative neutrophils. In contrast, no significant differences were observed in
      the secretion of lactoferrin, a marker of specific granules, and matrix
      methalloproteinase-9, a marker of gelatinase granules between cross-matching
      positive and cross-matching-negative cells upon stimulation with sera. CD11b
      expression and secretion of HBP by serum was partially inhibited by p38 mitogen
      activated protein (MAP)-kinase inhibitors. CONCLUSION: Neutrophils activated with
      sera containing HLA Class I alloantibody caused the preferential degranulation of
      azurophilic granules and secretory vesicles. This process was at least in part
      mediated by p38 MAP kinase-involved signal transduction.

PMID- 20158697
TI  - The Dublin Consensus Statement on vital issues relating to the collection of
      blood and plasma and the manufacture of plasma products. PLUS.

PMID- 20158866
TI  - Mechanisms of chromosomal rearrangement in the human genome.
AB  - Many human cancers are associated with characteristic chromosomal rearrangements,
      especially hematopoietic cancers such as leukemias and lymphomas. The first and
      most critical step in the rearrangement process is the induction of two DNA
      double-strand breaks (DSB). In all cases, at least one of the two DSBs is
      generated by a pathologic process, such as (1) randomly-positioned breaks due to
      ionizing radiation, free radical oxidative damage, or spontaneous hydrolysis; (2)
      breaks associated with topoisomerase inhibitor treatment; or (3) breaks at direct
      or inverted repeat sequences, mediated by unidentified strand breakage
      mechanisms. In lymphoid cells, one of the two requisite DSBs is often
      physiologic, the result of V(D)J recombination or class switch recombination
      (CSR) at the lymphoid antigen receptor loci. The RAG complex, which causes the
      DSBs in V(D)J recombination, can cause (4) sequence-specific, pathologic DSBs at
      sites that fit the consensus of their normal V(D)J recombination signal targets;
      or (5) structure-specific, pathologic DSBs at regions of single- to double-strand
      transition. CSR occurs specifically in the B-cell lineage, and requires (6)
      activation-induced cytidine deaminase (AID) action at sites of single-stranded
      DNA, which may occur pathologically outside of the normal target loci of class
      switch recombination regions and somatic hypermutation (SHM) zones. Recent work
      proposes a seventh mechanism: the sequential action of AID and the RAG complex at
      CpG sites provides a coherent model for the pathologic DSBs at some of the most
      common sites of translocation in human lymphoma - the bcl-2 gene in follicular
      lymphoma and diffuse large B-cell lymphoma, and the bcl-1 gene in mantle cell
      lymphoma.

PMID- 20158867
TI  - Transposon identification using profile HMMs.
AB  - BACKGROUND: Transposons are "jumping genes" that account for large quantities of
      repetitive content in genomes. They are known to affect transcriptional
      regulation in several different ways, and are implicated in many human diseases.
      Transposons are related to microRNAs and viruses, and many genes, pseudogenes,
      and gene promoters are derived from transposons or have origins in transposon
      induced duplication. Modeling transposon-derived genomic content is difficult
      because they are poorly conserved. Profile hidden Markov models (profile HMMs),
      widely used for protein sequence family modeling, are rarely used for modeling
      DNA sequence families. The algorithm commonly used to estimate the parameters of
      profile HMMs, Baum-Welch, is prone to prematurely converge to local optima. The
      DNA domain is especially problematic for the Baum-Welch algorithm, since it has
      only four letters as opposed to the twenty residues of the amino acid alphabet.
      RESULTS: We demonstrate with a simulation study and with an application to
      modeling the MIR family of transposons that two recently introduced methods,
      Conditional Baum-Welch and Dynamic Model Surgery, achieve better estimates of the
      parameters of profile HMMs across a range of conditions. CONCLUSIONS: We argue
      that these new algorithms expand the range of potential applications of profile
      HMMs to many important DNA sequence family modeling problems, including that of
      searching for and modeling the virus-like transposons that are found in all known
      genomes.

PMID- 20158868
TI  - Modeling neutral evolution of Alu elements using a branching process.
AB  - BACKGROUND: Alu elements occupy about eleven percent of the human genome and are
      still growing in copy numbers. Since Alu elements substantially impact the shape
      of our genome, there is a need for modeling the amplification, mutation and
      selection forces of these elements. METHODS: Our proposed theoretical neutral
      model follows a discrete-time branching process described by Griffiths and Pakes.
      From this model, we derive a limit frequency spectrum of the Alu element
      distribution, which serves as the theoretical, neutral frequency to which real
      Alu insertion data can be compared through statistical goodness of fit tests.
      Departures from the neutral frequency spectrum may indicate selection. RESULTS: A
      comparison of the Alu sequence data, obtained by courtesy of Dr. Jerzy Jurka,
      with our model shows that the distributions of Alu sequences in the AluY family
      systematically deviate from the expected distribution derived from the branching
      process. CONCLUSIONS: This observation suggests that Alu sequences do not evolve
      neutrally and might be under selection.

PMID- 20158869
TI  - Statistics of protein-DNA binding and the total number of binding sites for a
      transcription factor in the mammalian genome.
AB  - BACKGROUND: Transcription factor (TF)-DNA binding loci are explored by analyzing
      massive datasets generated with application of Chromatin Immuno-Precipitation
      (ChIP)-based high-throughput sequencing technologies. These datasets suffer from
      a bias in the information about binding loci availability, sample incompleteness
      and diverse sources of technical and biological noises. Therefore adequate
      mathematical models of ChIP-based high-throughput assay(s) and statistical tools
      are required for a robust identification of specific and reliable TF binding
      sites (TFBS), a precise characterization of TFBS avidity distribution and a
      plausible estimation the total number of specific TFBS for a given TF in the
      genome for a given cell type. RESULTS: We developed an exploratory mixture
      probabilistic model for a specific and non-specific transcription factor-DNA (TF
      DNA) binding. Within ChiP-seq data sets, the statistics of specific and non
      specific DNA-protein binding is defined by a mixture of sample size-dependent
      skewed functions described by Kolmogorov-Waring (K-W) function (Kuznetsov, 2003)
      and exponential function, respectively. Using available Chip-seq data for eleven
      TFs, essential for self-maintenance and differentiation of mouse embryonic stem
      cells (SC) (Nanog, Oct4, sox2, KLf4, STAT3, E2F1, Tcfcp211, ZFX, n-Myc, c-Myc and
      Essrb) reported in Chen et al (2008), we estimated (i) the specificity and the
      sensitivity of the ChiP-seq binding assays and (ii) the number of specific but
      not identified in the current experiments binding sites (BSs) in the genome of
      mouse embryonic stem cells. Motif finding analysis applied to the identified c
      Myc TFBSs supports our results and allowed us to predict many novel c-Myc target
      genes. CONCLUSION: We provide a novel methodology of estimating the specificity
      and the sensitivity of TF-DNA binding in massively paralleled ChIP sequencing
      (ChIP-seq) binding assay. Goodness-of fit analysis of K-W functions suggests that
      a large fraction of low- and moderate- avidity TFBSs cannot be identified by the
      ChIP-based methods. Thus the task to identify the binding sensitivity of a TF
      cannot be technically resolved yet by current ChIP-seq, compared to former
      experimental techniques. Considering our improvement in measuring the sensitivity
      and the specificity of the TFs obtained from the ChIP-seq data, the models of
      transcriptional regulatory networks in embryonic cells and other cell types
      derived from the given ChIp-seq data should be carefully revised.

PMID- 20158870
TI  - Reducing the haystack to find the needle: improved protein identification after
      fast elimination of non-interpretable peptide MS/MS spectra and noise reduction.
AB  - BACKGROUND: Tandem mass spectrometry (MS/MS) has become a standard method for
      identification of proteins extracted from biological samples but the huge number
      and the noise contamination of MS/MS spectra obstruct swift and reliable computer
      aided interpretation. Typically, a minor fraction of the spectra per sample (most
      often, only a few %) and about 10% of the peaks per spectrum contribute to the
      final result if protein identification is not prevented by the noise at all.
      RESULTS: Two fast preprocessing screens can substantially reduce the haystack of
      MS/MS data. (1) Simple sequence ladder rules remove spectra non-interpretable in
      peptide sequences. (2) Modified Fourier-transform-based criteria clear background
      in the remaining data. In average, only a remainder of 35% of the MS/MS spectra
      (each reduced in size by about one quarter) has to be handed over to the
      interpretation software for reliable protein identification essentially without
      loss of information, with a trend to improved sequence coverage and with
      proportional decrease of computer resource consumption. CONCLUSIONS: The search
      for sequence ladders in tandem MS/MS spectra with subsequent noise suppression is
      a promising strategy to reduce the number of MS/MS spectra from electro-spray
      instruments and to enhance the reliability of protein matches. Supplementary
      material and the software are available from an accompanying WWW-site with the
      URL http://mendel.bii.a-star.edu.sg/mass-spectrometry/MSCleaner-2.0/.

PMID- 20158871
TI  - Bioinformatic search of plant microtubule-and cell cycle related serine-threonine
      protein kinases.
AB  - A bioinformatic search was carried for plant homologues of human serine-threonine
      protein kinases involved in regulation of cell division and microtubule protein
      phosphorylation (SLK, PAK6, PAK7, MARK1, MAST2, TTBK1, TTBK2, AURKA, PLK1, PLK4
      and PASK). A number of SLK, MAST2 and AURKA plant homologues were identified. The
      closest identified homologue of human AURKA kinase was a protein of unknown
      function, A7PY12/GSVIVT00026259001 from Vitis vinifera (herein named as "STALK",
      Serine-Threonine Aurora-Like Kinase). Analysis of STALK's three-dimensional
      structure confirmed its relationship to the subgroup of AURKA-like protein
      kinases.

PMID- 20158872
TI  - Parameterization of disorder predictors for large-scale applications requiring
      high specificity by using an extended benchmark dataset.
AB  - BACKGROUND: Algorithms designed to predict protein disorder play an important
      role in structural and functional genomics, as disordered regions have been
      reported to participate in important cellular processes. Consequently, several
      methods with different underlying principles for disorder prediction have been
      independently developed by various groups. For assessing their usability in
      automated workflows, we are interested in identifying parameter settings and
      threshold selections, under which the performance of these predictors becomes
      directly comparable. RESULTS: First, we derived a new benchmark set that accounts
      for different flavours of disorder complemented with a similar amount of order
      annotation derived for the same protein set. We show that, using the recommended
      default parameters, the programs tested are producing a wide range of predictions
      at different levels of specificity and sensitivity. We identify settings, in
      which the different predictors have the same false positive rate. We assess
      conditions when sets of predictors can be run together to derive consensus or
      complementary predictions. This is useful in the framework of proteome-wide
      applications where high specificity is required such as in our in-house sequence
      analysis pipeline and the ANNIE webserver. CONCLUSIONS: This work identifies
      parameter settings and thresholds for a selection of disorder predictors to
      produce comparable results at a desired level of specificity over a newly derived
      benchmark dataset that accounts equally for ordered and disordered regions of
      different lengths.

PMID- 20158873
TI  - Collective motions and specific effectors: a statistical mechanics perspective on
      biological regulation.
AB  - BACKGROUND: The interaction of a multiplicity of scales in both time and space is
      a fundamental feature of biological systems. The complementation of macroscopic
      (entire organism) and microscopic (molecular biology) views with a mesoscopic
      level of analysis able to connect the different planes of investigation is
      urgently needed. This will allow to both obtain a general frame of reference for
      rationalizing the burden of data coming from high throughput technologies and to
      derive effective operational views on biological systems. RESULTS: The network
      paradigm in which microscopic level elements (nodes) are each other related by
      functional links so giving rise to both global (entire network) and local
      (specific) behavior is a promising metaphor to try and develop a statistical
      mechanics inspired approach for biological systems. Here we show the application
      of this paradigm to different systems going from yeast metabolism to murine
      macrophages response to immune stimulation. CONCLUSIONS: The need to complement
      the purely molecular view with mesoscopic approaches is evident in all the
      studied examples that in turn demonstrate the untenability of the simple ergodic
      approach dominant in molecular biology in which the data coming from huge
      ensemble of cells are considered as relative to a single 'average' cell.

PMID- 20158875
TI  - Projection of gene-protein networks to the functional space of the proteome and
      its application to analysis of organism complexity.
AB  - We consider the problem of biological complexity via a projection of protein
      coding genes of complex organisms onto the functional space of the proteome. The
      latter can be defined as a set of all functions committed by proteins of an
      organism. Alternative splicing (AS) allows an organism to generate diverse mature
      RNA transcripts from a single mRNA strand and thus it could be one of the key
      mechanisms of increasing of functional complexity of the organism's proteome and
      a driving force of biological evolution. Thus, the projection of transcription
      units (TU) and alternative splice-variant (SV) forms onto proteome functional
      space could generate new types of relational networks (e.g. SV-protein function
      networks, SFN) and lead to discoveries of novel evolutionarily conservative
      functional modules. Such types of networks might provide new reliable
      characteristics of organism complexity and a better understanding of the
      evolutionary integration and plasticity of interconnection of genome
      transcriptome-proteome functions. RESULTS: We use the InterPro and UniProt
      databases to attribute descriptive features (keywords) to protein sequences.
      UniProt database includes a controlled and curated vocabulary of specific
      descriptors or keywords. The keywords have been assigned to a protein sequence
      via conserved domains or via similarity with annotated sequences. Then we
      consider the unique combinations of keywords as the protein functional labels
      (FL), which characterize the biological functions of the given protein and
      construct the contingency tables and graphs providing the projections of
      transcription units (TU) and alternative splice-variants (SV) onto all FL of the
      proteome of a given organism. We constructed SFNs for organisms with different
      evolutionary history and levels of complexity, and performed detailed statistical
      parameterization of the networks. CONCLUSIONS: The application of the algorithm
      to organisms with different evolutionary history and level of biological
      complexity (nematode, fruit fly, vertebrata) reveals that the parameters
      describing SFN correlate with the complexity of a given organism. Using
      statistical analysis of the links of the functional networks, we propose new
      features of evolution of protein function acquisition. We reveal a group of genes
      and corresponding functions, which could be attributed to an early conservative
      part of the cellular machinery essential for cell viability and survival. We
      identify and provide characteristics of functional switches in the polyform group
      of TUs in different organisms. Based on comparison of mouse and human SFNs, a
      role of alternative splicing as a necessary source of evolution towards more
      complex organisms is demonstrated. The entire set of FL across many organisms
      could be used as a draft of the catalogue of the functional space of the proteome
      world.

PMID- 20158874
TI  - Computational approaches for detecting protein complexes from protein interaction
      networks: a survey.
AB  - BACKGROUND: Most proteins form macromolecular complexes to perform their
      biological functions. However, experimentally determined protein complex data,
      especially of those involving more than two protein partners, are relatively
      limited in the current state-of-the-art high-throughput experimental techniques.
      Nevertheless, many techniques (such as yeast-two-hybrid) have enabled systematic
      screening of pairwise protein-protein interactions en masse. Thus computational
      approaches for detecting protein complexes from protein interaction data are
      useful complements to the limited experimental methods. They can be used together
      with the experimental methods for mapping the interactions of proteins to
      understand how different proteins are organized into higher-level substructures
      to perform various cellular functions. RESULTS: Given the abundance of pairwise
      protein interaction data from high-throughput genome-wide experimental
      screenings, a protein interaction network can be constructed from protein
      interaction data by considering individual proteins as the nodes, and the
      existence of a physical interaction between a pair of proteins as a link. This
      binary protein interaction graph can then be used for detecting protein complexes
      using graph clustering techniques. In this paper, we review and evaluate the
      state-of-the-art techniques for computational detection of protein complexes, and
      discuss some promising research directions in this field. CONCLUSIONS:
      Experimental results with yeast protein interaction data show that the
      interaction subgraphs discovered by various computational methods matched well
      with actual protein complexes. In addition, the computational approaches have
      also improved in performance over the years. Further improvements could be
      achieved if the quality of the underlying protein interaction data can be
      considered adequately to minimize the undesirable effects from the irrelevant and
      noisy sources, and the various biological evidences can be better incorporated
      into the detection process to maximize the exploitation of the increasing wealth
      of biological knowledge available.

PMID- 20158876
TI  - Differences in the transactivation domains of p53 family members: a computational
      study.
AB  - The N terminal transactivation domain of p53 is regulated by ligases and
      coactivator proteins. The functional conformation of this region appears to be an
      alpha helix which is necessary for its appropriate interactions with several
      proteins including MDM2 and p300. Folding simulation studies have been carried
      out to examine the propensity and stability of this region and are used to
      understand the differences between the family members with the ease of helix
      formation following the order p53 > p73 > p63. It is clear that hydrophobic
      clusters control the kinetics of helix formation, while electrostatic
      interactions control the thermodynamic stability of the helix. Differences in
      these interactions between the family members may partially account for the
      differential binding to, and regulation by, MDM2 (and MDMX). Phosphorylations of
      the peptides further modulate the stability of the helix and control associations
      with partner proteins.

PMID- 20158877
TI  - Analysis of deep sequencing microRNA expression profile from human embryonic stem
      cells derived mesenchymal stem cells reveals possible role of let-7 microRNA
      family in downstream targeting of hepatic nuclear factor 4 alpha.
AB  - BACKGROUND: Recent literature has revealed that genetic exchange of microRNA
      between cells can be essential for cell-cell communication, tissue-specificity
      and developmental processes. In stem cells, as in other cells, this can be
      accomplished through microvesicles or exosome mediated transfer. However,
      molecular profiles and functions of microRNAs within the cells and in their
      exosomes are poorly studied. Next generation sequencing technologies could
      provide a broad-spectrum of microRNAs and their expression and identify possible
      microRNA targets. In this work, we performed deep sequencing of microRNAs to
      understand the profile and expression of the microRNAs in microvesicles and
      intracellular environment of human embryonic stem cells derived mesenchymal stem
      cells (hES-MSC). We outline a workflow pertaining to visualizing, statistical
      analysis and interpreting deep sequencing data of known intracellular and
      extracellular microRNAs from hES-MSC). We utilized these results of which
      directed our attention towards establishing hepatic nuclear factor 4 alpha
      (HNF4A) as a downstream target of let-7 family of microRNAs. RESULTS: In our
      study, significant differences in expression profile of microRNAs were found in
      the intracellular and extracellular environment of hES-MSC. However, a high level
      of let-7 family of microRNAs is predominant in both intra- and extra- cellular
      samples of hES-MSC. Further results derived from visualization of our alignment
      data and network analysis showed that let-7 family microRNAs could affect the
      downstream target HNF4A, which is a known endodermal differentiation marker. The
      elevated presence of let-7 microRNA in both intracellular and extra cellular
      environment further suggests a possible intercellular signalling mechanism
      through microvesicles transfer. We suggest that let-7 family microRNAs might play
      a signalling role via such a mechanism amongst populations of stem cells in
      maintaining self renewal property by suppressing HNF4A expression. This is in
      line with recent paradigm where microRNAs regulate self-renewal and
      differentiation pathways of embryonic stem cells by forming an integral
      biological network with transcription factors. CONCLUSION: In summary, our study
      using a combination of alignment, statistical and network analysis tools to
      examine deep sequencing data of microRNAs in hES-MSC has led to a result that (i)
      identifies intracellular and exosome microRNA expression profiles of hES-MSC with
      a possible mechanism of miRNA mediated intercellular regulation by these cells
      and (ii) placed HNF4A within the cross roads of regulation by the let-7 family of
      microRNAs.

PMID- 20158878
TI  - Data integration and exploration for the identification of molecular mechanisms
      in tumor-immune cells interaction.
AB  - Cancer progression is a complex process involving host-tumor interactions by
      multiple molecular and cellular factors of the tumor microenvironment. Tumor
      cells that challenge immune activity may be vulnerable to immune destruction. To
      address this question we have directed major efforts towards data integration and
      developed and installed a database for cancer immunology with more than 1700
      patients and associated clinical data and biomolecular data. Mining of the
      database revealed novel insights into the molecular mechanisms of tumor-immune
      cell interaction. In this paper we present the computational tools used to
      analyze integrated clinical and biomolecular data. Specifically, we describe a
      database for heterogeneous data types, the interfacing bioinformatics and
      statistical tools including clustering methods, survival analysis, as well as
      visualization methods. Additionally, we discuss generic issues relevant to the
      integration of clinical and biomolecular data, as well as recent developments in
      integrative data analyses including biomolecular network reconstruction and
      mathematical modeling.

PMID- 20158879
TI  - Bimodal gene expression patterns in breast cancer.
AB  - We identified a set of genes with an unexpected bimodal distribution among breast
      cancer patients in multiple studies. The property of bimodality seems to be
      common, as these genes were found on multiple microarray platforms and in studies
      with different end-points and patient cohorts. Bimodal genes tend to cluster into
      small groups of four to six genes with synchronised expression within the group
      (but not between the groups), which makes them good candidates for robust
      conditional descriptors. The groups tend to form concise network modules
      underlying their function in cancerogenesis of breast neoplasms.

PMID- 20158880
TI  - Complex sense-antisense architecture of TNFAIP1/POLDIP2 on 17q11.2 represents a
      novel transcriptional structural-functional gene module involved in breast cancer
      progression.
AB  - BACKGROUND: A sense-antisense gene pair (SAGP) is a gene pair where two
      oppositely transcribed genes share a common nucleotide sequence region. In
      eukaryotic genomes, SAGPs can be organized in complex sense-antisense
      architectures (CSAGAs) in which at least one sense gene shares loci with two or
      more antisense partners. As shown in several case studies, SAGPs may be involved
      in cancers, neurological diseases and complex syndromes. However, CSAGAs have not
      yet been characterized in the context of human disease or cancer. RESULTS: We
      characterize five genes (TMEM97, IFT20, TNFAIP1, POLDIP2 and TMEM199) organized
      in a CSAGA on 17q11.2 (we term this the TNFAIP1/POLDIP2 CSAGA) and demonstrate
      their strong and reproducible co-regulatory transcription pattern in breast
      cancer tumours. Genes of the TNFAIP1/POLDIP2 CSAGA are located inside the
      smallest region of recurrent amplification on 17q11.2 and their expression
      profile correlates with the DNA copy number of the region. Survival analysis of a
      group of 410 breast cancer patients revealed significant survival-associated
      individual genes and gene pairs in the TNFAIP1/POLDIP2 CSAGA. Moreover, several
      of the gene pairs associated with survival, demonstrated synergistic effects.
      Expression of genes-members of the TNFAIP1/POLDIP2 CSAGA also strongly correlated
      with expression of genes of ERBB2 core region of recurrent amplification on
      17q12. We clearly demonstrate that the observed co-regulatory transcription
      profile of the TNFAIP1/POLDIP2 CSAGA is maintained not only by a DNA
      amplification mechanism, but also by chromatin remodelling and local
      transcription activation. CONCLUSION: We have identified a novel TNFAIP1/POLDIP2
      CSAGA and characterized its co-regulatory transcription profile in cancerous
      breast tissues. We suggest that the TNFAIP1/POLDIP2 CSAGA represents a clinically
      significant transcriptional structural-functional gene module associated with
      amplification of the genomic region on 17q11.2 and correlated with expression
      ERBB2 amplicon core genes in breast cancer. Co-expression pattern of this module
      correlates with histological grades and a poor prognosis in breast cancer when
      over-expressed. TNFAIP1/POLDIP2 CSAGA maps the risks of breast cancer relapse
      onto the complex genomic locus on 17q11.2.

PMID- 20158881
TI  - Survival and self-renewing capacity of breast cancer initiating cells during
      fractionated radiation treatment.
AB  - INTRODUCTION: Recent data indicate a hierarchical organization of many solid
      cancers, including breast cancer, with a small number of cancer initiating cells
      (CICs) that have the ability to self-renew and exhibit multi-lineage potency. We,
      and others, have demonstrated that CICs in breast cancer and glioma are
      relatively resistant to ionizing radiation if compared to their non-tumorigenic
      counterparts. However, the extent of the remaining self-renewing capacity of CICs
      after fractions of radiation is currently unknown. We hypothesized that CICs, in
      contrast to their non-tumorigenic counterparts, not only survive fractions of
      ionizing radiation but also retain the CIC phenotype as defined by operational
      means. METHODS: We used two marker systems to identify breast CICs (CD24
      /low/CD44high, or lack of proteasome activity) and performed sphere-forming
      assays after multiple clinical fractions of radiation. Lineage tracking was
      performed by membrane staining. Cell cycle distribution and RNA content were
      assessed by flow cytometry and senescence was assessed via beta-galactosidase
      staining. RESULTS: We demonstrated that irradiated CICs survived and retained
      their self-renewal capacity for at least four generations. We show that
      fractionated radiation not only spared CICs but also mobilized them from a
      quiescent/G0 phase of the cell cycle into actively cycling cells, while the
      surviving non-tumorigenic cells were driven into senescence. CONCLUSIONS: The
      breast CIC population retains increased self-renewal capacity over several
      generations and therefore, we conclude that increases in the number of CICs after
      sublethal doses of radiation have potential clinical importance. Prevention of
      this process may lead to improved clinical outcome.

PMID- 20158882
TI  - Sialic acid mediated transcriptional modulation of a highly conserved
      sialometabolism gene cluster in Haemophilus influenzae and its effect on
      virulence.
AB  - BACKGROUND: Sialic acid has been shown to be a major virulence determinant in the
      pathogenesis of otitis media caused by the bacterium Haemophilus influenzae. This
      study aimed to characterise the expression of genes required for the metabolism
      of sialic acid and to investigate the role of these genes in virulence. RESULTS:
      Using qRT-PCR, we observed decreased transcriptional activity of genes within a
      cluster that are required for uptake and catabolism of 5-acetyl neuraminic acid
      (Neu5Ac), when bacteria were cultured in the presence of the sugar. We show that
      these uptake and catabolic genes, including a sialic acid regulatory gene (siaR),
      are highly conserved in the H. influenzae natural population. Mutant strains were
      constructed for seven of the nine genes and their influence upon LPS sialylation
      and resistance of the bacteria to the killing effect of normal human serum were
      assessed. Mutations in the Neu5Ac uptake (TRAP transporter) genes decreased
      virulence in the chinchilla model of otitis media, but the attenuation was strain
      dependent. In contrast, mutations in catabolism genes and genes regulating sialic
      acid metabolism (siaR and crp) did not attenuate virulence. CONCLUSION: The
      commensal and pathogenic behaviour of H. influenzae involves LPS sialylation that
      can be influenced by a complex regulatory interplay of sialometabolism genes.

PMID- 20158883
TI  - Complications of circumcision in male neonates, infants and children: a
      systematic review.
AB  - BACKGROUND: Approximately one in three men are circumcised globally, but there
      are relatively few data on the safety of the procedure. The aim of this paper is
      to summarize the literature on frequency of adverse events following pediatric
      circumcision, with a focus on developing countries. METHODS: PubMed and other
      databasess were searched with keywords and MeSH terms including
      infant/newborn/pediatric/child, circumcision, complications and adverse events.
      Searches included all available years and were conducted on November 6th 2007 and
      updated on February 14th 2009. Additional searches of the Arabic literature
      included searches of relevant databases and University libraries for research
      theses on male circumcision.Studies were included if they contained data to
      estimate frequency of adverse events following neonatal, infant and child
      circumcision. There was no language restriction. A total of 1349 published papers
      were identified, of which 52 studies from 21 countries met the inclusion
      criteria. The Arabic literature searches identified 46 potentially relevant
      papers, of which six were included. RESULTS: Sixteen prospective studies
      evaluated complications following neonatal and infant circumcision. Most studies
      reported no severe adverse events (SAE), but two studies reported SAE frequency
      of 2%. The median frequency of any complication was 1.5% (range 0-16%). Child
      circumcision by medical providers tended to be associated with more complications
      (median frequency 6%; range 2-14%) than for neonates and infants. Traditional
      circumcision as a rite of passage is associated with substantially greater risks,
      more severe complications than medical circumcision or traditional circumcision
      among neonates. CONCLUSIONS: Studies report few severe complications following
      circumcision. However, mild or moderate complications are seen, especially when
      circumcision is undertaken at older ages, by inexperienced providers or in non
      sterile conditions. Pediatric circumcision will continue to be practiced for
      cultural, medical and as a long-term HIV/STI prevention strategy. Risk-reduction
      strategies including improved training of providers, and provision of appropriate
      sterile equipment, are urgently needed.

PMID- 20158884
TI  - Housing system and herd size interactions in Norwegian dairy herds; associations
      with performance and disease incidence.
AB  - BACKGROUND: According to the Norwegian animal welfare regulations, it has been
      forbidden to build new tie-stall barns since the end of 2004. Previous studies
      have shown that cow performance and health differ between housing systems. The
      interaction between housing system and herd size with respect to performance and
      disease incidence has not been evaluated. METHODS: Cow performance and health in
      620 herds housed in free-stall barns were compared with in 192 herds housed in
      tie-stall barns based on a mail survey and data from the Norwegian Dairy Herd
      Recording and Cattle Health Systems. The housing systems herds were comparable
      with respect to herd size (15-55 cows). Associations between performance/disease
      incidence and housing system, herd size and year of building the cow barn were
      tested in general linear models, and values for fixed herd size of 20 and 50 cows
      were calculated. On the individual cow level mixed models were run to test the
      effect of among others housing system and herd size on test-day milk yield, and
      to evaluate lactation curves in different parities. All cows were of the
      Norwegian Red Breed. RESULTS: Average milk production per cow-year was 134 kg
      lower in free-stall herd than in tie-stall herds, but in the range 27-45 cows
      there was no significant difference in yields between the herd categories. In
      herds with less than 27 cows there were increasingly lower yields in free-stalls,
      particularly in first parity, whereas the yields were increasingly higher in free
      stalls with more than 45 cows.In free-stalls fertility was better, calving
      interval shorter, and the incidence rate of teat injuries, ketosis, indigestions,
      anoestrus and cystic ovaries was lower than in tie-stalls. All of these factors
      were more favourable in estimated 50-cow herds as compared to 20-cow herds. In
      the larger herd category, bulk milk somatic cell counts were higher, and the
      incidence rate of mastitis (all cases) and all diseases was lower. CONCLUSION:
      This study has shown that there is an interaction between housing system and herd
      size, and that performance and health is not universally better in small free
      stalls than in tie-stalls.

PMID- 20158885
TI  - High-mobility group box-1 protein, lipopolysaccharide-binding protein,
      interleukin-6 and C-reactive protein in children with community acquired
      infections and bacteraemia: a prospective study.
AB  - INTRODUCTION: Even though sepsis is one of the common causes of children
      morbidity and mortality, specific inflammatory markers for identifying sepsis are
      less studied in children. The main aim of this study was to compare the levels of
      high-mobility group box-1 protein (HMGB1), Lipopolysaccharide-binding protein
      (LBP), Interleukin-6 (IL-6) and C-reactive protein (CRP) between infected
      children without systemic inflammatory response syndrome (SIRS) and children with
      severe and less severe sepsis. The second aim was to examine HMGB1, LBP, IL6 and
      CRP as markers for of bacteraemia. METHODS: Totally, 140 children with suspected
      or proven infections admitted to the Children's Clinical University Hospital of
      Latvia during 2008 and 2009 were included. Clinical and demographical information
      as well as infection focus were assessed in all patients. HMGB1, LBP, IL-6 and
      CRP blood samples were determined. Children with suspected or diagnosed
      infections were categorized into three groups of severity of infection: (i)
      infected without SIRS (n = 36), (ii) sepsis (n = 91) and, (iii) severe sepsis (n
      = 13). They were furthermore classified according bacteraemia into (i) bacteremia
      (n = 30) and (ii) no bacteraemia (n = 74). RESULTS: There was no statistically
      significant difference in HMGB1 levels between children with different levels of
      sepsis or with and without bacteraemia. The levels of LBP, IL-6 and CRP were
      statistically significantly higher among patients with sepsis compared to those
      infected but without SIRS (p < 0.001). Furthermore, LBP, IL-6 and CRP were
      significantly higher in children with severe sepsis compared to those ones with
      less severe sepsis (p < 0.001). Median values of LBP, IL6 and CRP were
      significantly higher in children with bacteraemia compared to those without
      bacteraemia. The area under the receiver operating curve (ROC) for detecting
      bacteraemia was 0.87 for both IL6 and CRP and 0.82 for LBP, respectively.
      CONCLUSION: Elevated levels of LBP, IL-6 and CRP were associated with a more
      severe level of infection in children. Whereas LBP, IL-6 and CRP seem to be good
      markers to detect patients with bacteraemia, HMGB1 seem to be of minor
      importance. LBP, IL-6 and CRP levels may serve as good biomarkers for identifying
      children with severe sepsis and bacteraemia and, thus, may be routinely used in
      clinical practice.

PMID- 20158886
TI  - The effects of local street network characteristics on the positional accuracy of
      automated geocoding for geographic health studies.
AB  - BACKGROUND: Automated geocoding of patient addresses for the purpose of
      conducting spatial epidemiologic studies results in positional errors. It is well
      documented that errors tend to be larger in rural areas than in cities, but
      possible effects of local characteristics of the street network, such as street
      intersection density and street length, on errors have not yet been documented.
      Our study quantifies effects of these local street network characteristics on the
      means and the entire probability distributions of positional errors, using
      regression methods and tolerance intervals/regions, for more than 6000 geocoded
      patient addresses from an Iowa county. RESULTS: Positional errors were determined
      for 6376 addresses in Carroll County, Iowa, as the vector difference between each
      100%-matched automated geocode and its ground-truthed location. Mean positional
      error magnitude was inversely related to proximate street intersection density.
      This effect was statistically significant for both rural and municipal addresses,
      but more so for the former. Also, the effect of street segment length on
      geocoding accuracy was statistically significant for municipal, but not rural,
      addresses; for municipal addresses mean error magnitude increased with length.
      CONCLUSION: Local street network characteristics may have statistically
      significant effects on geocoding accuracy in some places, but not others. Even in
      those locales where their effects are statistically significant, street network
      characteristics may explain a relatively small portion of the variability among
      geocoding errors. It appears that additional factors besides rurality and local
      street network characteristics affect accuracy in general.

PMID- 20158887
TI  - Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in
      rheumatoid arthritis.
AB  - INTRODUCTION: Dectin-1, a pattern recognition receptor expressed by the innate
      immune system, is known to be a major receptor inducing Th17-type adaptive immune
      responses that have been demonstrated to mediate autoimmunity. In this study,
      dectin-1 mRNA and protein expression, as well as the recently characterized
      DECTIN-1 Y238X early stop codon polymorphism, were studied in relation to
      rheumatoid arthritis (RA) susceptibility and severity. METHODS: Dectin-1 mRNA
      expression was measured in synovial tissue specimens of RA, osteoarthritis (OA),
      and nonrheumatic patients. Dectin-1 protein expression and localization were
      assessed in RA synovial tissue specimens. Macrophages from individuals with
      different DECTIN-1 genotypes were examined for differences in cytokine responses
      on dectin-1 stimulation. Furthermore, clinical parameters of inflammation and
      bone destruction of 262 RA patients were correlated with the presence of the
      DECTIN-1 Y238X polymorphism. RESULTS: Evaluation of dectin-1 mRNA expression in
      synovial tissue biopsies revealed an increased expression in RA specimens,
      compared with biopsies from OA and nonrheumatic patients. Accordingly, dectin-1
      protein expression in RA synovial tissue biopsies was moderate to high,
      especially on macrophage-like cells. Cytokine production capacity of macrophages
      bearing the DECTIN-1 Y238X polymorphism was demonstrated to be impaired on dectin
      1 stimulation. However, the presence of the DECTIN-1 Y238X polymorphism was not
      associated with RA susceptibility or disease severity. CONCLUSIONS: Although
      expression of dectin-1 was high in synovial tissue of RA patients, and reduced
      cytokine production was observed in macrophages of individuals bearing the DECTIN
      1 Y238X polymorphism, loss of one functional allele of DECTIN-1 is not associated
      with either susceptibility to or severity of RA.

PMID- 20158888
TI  - On the general theory of the origins of retroviruses.
AB  - BACKGROUND: The order retroviridae comprises viruses based on ribonucleic acids
      (RNA). Some, such as HIV and HTLV, are human pathogens. Newly emerged human
      retroviruses have zoonotic origins. As far as has been established, both repeated
      infections (themselves possibly responsible for the evolution of viral mutations
      (Vm) and host adaptability (Ha)); along with interplay between inhibitors and
      promoters of cell tropism, are needed to effect retroviral cross-species
      transmissions. However, the exact modus operandi of intertwine between these
      factors at molecular level remains to be established. Knowledge of such
      intertwine could lead to a better understanding of retrovirology and possibly
      other infectious processes. This study was conducted to derive the mathematical
      equation of a general theory of the origins of retroviruses. METHODS AND RESULTS:
      On the basis of an arbitrarily non-Euclidian geometrical "thought experiment"
      involving the cross-species transmission of simian foamy virus (sfv) from a non
      primate species Xy to Homo sapiens (Hs), initially excluding all social factors,
      the following was derived. At the port of exit from Xy (where the species
      barrier, SB, is defined by the Index of Origin, IO), sfv shedding is (1) enhanced
      by two transmitting tensors (Tt), (i) virus-specific immunity (VSI) and (ii)
      evolutionary defenses such as APOBEC, RNA interference pathways, and (when
      present) expedited therapeutics (denoted e2D); and (2) opposed by the five
      accepting scalars (At): (a) genomic integration hot spots, gIHS, (b) nuclear
      envelope transit (NMt) vectors, (c) virus-specific cellular biochemistry, VSCB,
      (d) virus-specific cellular receptor repertoire, VSCR, and (e) pH-mediated cell
      membrane transit, (downward arrow pH CMat). Assuming As and Tt to be independent
      variables, IO = Tt/As. The same forces acting in an opposing manner determine SB
      at the port of sfv entry (defined here by the Index of Entry, IE = As/Tt).
      Overall, If sfv encounters no unforeseen effects on transit between Xy and Hs,
      then the square root of the combined index of sfv transmissibility (radical
      |RTI|) is proportional to the product IO* IE (or approximately Vm* Ha* sum Tt*
      sum As*Omega), where Omega is the retrovirological constant and summation
      operator is a function of the ratio Tt/As or As/Tt for sfv transmission from Xy
      to Hs. CONCLUSIONS: I present a mathematical formalism encapsulating the general
      theory of the origins of retroviruses. It summarizes the choreography for the
      intertwined interplay of factors influencing the probability of retroviral cross
      species transmission: Vm, Ha, Tt, As, and Omega.

PMID- 20158889
TI  - Adult case of partial trisomy 9q.
AB  - BACKGROUND: Complete and partial trisomy 9 is the fourth most common chromosomal
      disorder. It is also associated with various congenital characteristics affecting
      the cranio-facial, skeletal, central nervous, gastrointestinal, cardiac and renal
      systems. Very few cases have been reported in adults. Partial trisomy 9q is also
      associated with short stature, poor growth and growth hormone deficiency. This is
      the first reported case of an extensive endocrinology investigation of short
      stature in trisomy 9q and the outcome of growth hormone treatment. CASE
      PRESENTATION: The case involves a 23-year-old female of pure partial trisomy 9q.
      The case involves a 23-year old female with pure partial trisomy 9q involving a
      duplication of 9q22.1 to q32, de novo, confirmed by genetic studies using
      fluorescene in situ hybridization (FISH) method. The diagnosis was at 6 years of
      age. She did not demonstrate all the congenital morphologies identified with
      trisomy 9q disorders especially in relation to multi-organ morphologies. There is
      also a degree of associated intellectual impairment. At prepuberty, she was
      referred for poor growth and was diagnosed with partial growth hormone
      deficiency. She responded very well to treatment with growth hormone and is
      currently living an independent life with some support. CONCLUSIONS: Trisomy 9q
      is associated with short stature and failure to thrive. Growth hormone deficiency
      should be identified in cases of trisomy 9q and treatment offered. This is the
      first reported case of response to growth hormone replacement in partial trisomy
      9.

PMID- 20158890
TI  - Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the
      small bowel in patients with severe irritable bowel syndrome.
AB  - BACKGROUND: Inflammation and immune activation have repeatedly been suggested as
      pathogentic factors in irritable bowel syndrome (IBS). The driving force for
      immune activation in IBS remains unknown. The aim of our study was to find out if
      the obligate intracellular pathogen Chlamydia could be involved in the
      pathogenesis of IBS. METHODS: We studied 65 patients (61 females) with IBS and 42
      (29 females) healthy controls in which IBS had been excluded. Full thickness
      biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum
      were stained with a monoclonal antibody to Chlamydia lipopolysaccharide (LPS) and
      species-specific monoclonal antibodies to C. trachomatis and C. pneumoniae. We
      used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify
      enteroendocrine cells, macrophages, dendritic, and mast cells, respectively.
      RESULTS: Chlamydia LPS was present in 89% of patients with IBS, but in only 14%
      of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also
      positive for C. trachomatis major outer membrane protein (MOMP). Staining for C.
      pneumoniae was negative in both patients and controls. Chlamydia LPS was detected
      in enteroendocrine cells of the mucosa in 90% of positive biopsies and in
      subepithelial macrophages in 69% of biopsies. Biopsies taken at different time
      points in 19 patients revealed persistence of Chlamydia LPS up to 11 years. The
      odds ratio for the association of Chlamydia LPS with presence of IBS (43.1; 95%
      CI: 13.2-140.7) is much higher than any previously described pathogenetic marker
      in IBS. CONCLUSIONS: We found C. trachomatis antigens in enteroendocrine cells
      and macrophages in the small bowel mucosa of patients with IBS. Further studies
      are required to clarify if the presence of such antigens has a role in the
      pathogenesis of IBS.

PMID- 20158891
TI  - Assessing the role of undetected colonization and isolation precautions in
      reducing methicillin-resistant Staphylococcus aureus transmission in intensive
      care units.
AB  - BACKGROUND: Screening and isolation are central components of hospital
      methicillin-resistant Staphylococcus aureus (MRSA) control policies. Their
      prevention of patient-to-patient spread depends on minimizing undetected and
      unisolated MRSA-positive patient days. Estimating these MRSA-positive patient
      days and the reduction in transmission due to isolation presents a major
      methodological challenge, but is essential for assessing both the value of
      existing control policies and the potential benefit of new rapid MRSA detection
      technologies. Recent methodological developments have made it possible to
      estimate these quantities using routine surveillance data. METHODS: Colonization
      data from admission and weekly nares cultures were collected from eight single
      bed adult intensive care units (ICUs) over 17 months. Detected MRSA-positive
      patients were isolated using single rooms and barrier precautions. Data were
      analyzed using stochastic transmission models and model fitting was performed
      within a Bayesian framework using a Markov chain Monte Carlo algorithm, imputing
      unobserved MRSA carriage events. RESULTS: Models estimated the mean percent of
      colonized-patient-days attributed to undetected carriers as 14.1% (95% CI (11.7,
      16.5)) averaged across ICUs. The percent of colonized-patient-days attributed to
      patients awaiting results averaged 7.8% (6.2, 9.2). Overall, the ratio of
      estimated transmission rates from unisolated MRSA-positive patients and those
      under barrier precautions was 1.34 (0.45, 3.97), but varied widely across ICUs.
      CONCLUSIONS: Screening consistently detected >80% of colonized-patient-days.
      Estimates of the effectiveness of barrier precautions showed considerable
      uncertainty, but in all units except burns/general surgery and one cardiac
      surgery ICU, the best estimates were consistent with reductions in transmission
      associated with barrier precautions.

PMID- 20158892
TI  - Genomic features defining exonic variants that modulate splicing.
AB  - BACKGROUND: Single point mutations at both synonymous and non-synonymous
      positions within exons can have severe effects on gene function through
      disruption of splicing. Predicting these mutations in silico purely from the
      genomic sequence is difficult due to an incomplete understanding of the multiple
      factors that may be responsible. In addition, little is known about which
      computational prediction approaches, such as those involving exonic splicing
      enhancers and exonic splicing silencers, are most informative. RESULTS: We
      assessed the features of single-nucleotide genomic variants verified to cause
      exon skipping and compared them to a large set of coding SNPs common in the human
      population, which are likely to have no effect on splicing. Our findings
      implicate a number of features important for their ability to discriminate splice
      affecting variants, including the naturally occurring density of exonic splicing
      enhancers and exonic splicing silencers of the exon and intronic environment,
      extensive changes in the number of predicted exonic splicing enhancers and exonic
      splicing silencers, proximity to the splice junctions and evolutionary constraint
      of the region surrounding the variant. By extending this approach to additional
      datasets, we also identified relevant features of variants that cause increased
      exon inclusion and ectopic splice site activation. CONCLUSIONS: We identified a
      number of features that have statistically significant representation among
      exonic variants that modulate splicing. These analyses highlight putative
      mechanisms responsible for splicing outcome and emphasize the role of features
      important for exon definition. We developed a web-tool, Skippy, to score coding
      variants for these relevant splice-modulating features.

PMID- 20158893
TI  - Mild hypothermia alone or in combination with anesthetic post-conditioning
      reduces expression of inflammatory cytokines in the cerebral cortex of pigs after
      cardiopulmonary resuscitation.
AB  - INTRODUCTION: Hypothermia improves survival and neurological recovery after
      cardiac arrest. Pro-inflammatory cytokines have been implicated in focal cerebral
      ischemia/reperfusion injury. It is unknown whether cardiac arrest also triggers
      the release of cerebral inflammatory molecules, and whether therapeutic
      hypothermia alters this inflammatory response. This study sought to examine
      whether hypothermia or the combination of hypothermia with anesthetic post
      conditioning with sevoflurane affect cerebral inflammatory response after
      cardiopulmonary resuscitation. METHODS: Thirty pigs (28 to 34 kg) were subjected
      to cardiac arrest following temporary coronary artery occlusion. After seven
      minutes of ventricular fibrillation and two minutes of basic life support,
      advanced cardiac life support was started according to the current American Heart
      Association guidelines. Return of spontaneous circulation was achieved in 21
      animals who were randomized to either normothermia at 38 degrees C, hypothermia
      at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each
      group: n = 7) for 24 hours. The effects of hypothermia and the combination of
      hypothermia with sevoflurane on cerebral inflammatory response after
      cardiopulmonary resuscitation were studied using tissue samples from the cerebral
      cortex of pigs euthanized after 24 hours and employing quantitative RT-PCR and
      ELISA techniques. RESULTS: Global cerebral ischemia following resuscitation
      resulted in significant upregulation of cerebral tissue inflammatory cytokine
      mRNA expression (mean +/- SD; interleukin (IL)-1beta 8.7 +/- 4.0, IL-6 4.3 +/-
      2.6, IL-10 2.5 +/- 1.6, tumor necrosis factor (TNF)alpha 2.8 +/- 1.8,
      intercellular adhesion molecule-1 (ICAM-1) 4.0 +/- 1.9-fold compared with sham
      control) and IL-1beta protein concentration (1.9 +/- 0.6-fold compared with sham
      control). Hypothermia was associated with a significant (P < 0.05 versus
      normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL
      1beta 1.7 +/- 1.0, IL-6 2.2 +/- 1.1, IL-10 0.8 +/- 0.4, TNFalpha 1.1 +/- 0.6,
      ICAM-1 1.9 +/- 0.7-fold compared with sham control). These results were also
      confirmed for IL-1beta on protein level. Experimental settings employing
      hypothermia in combination with sevoflurane showed that the volatile anesthetic
      did not confer additional anti-inflammatory effects compared with hypothermia
      alone. CONCLUSIONS: Mild therapeutic hypothermia resulted in decreased expression
      of typical cerebral inflammatory mediators after cardiopulmonary resuscitation.
      This may confer, at least in part, neuroprotection following global cerebral
      ischemia and resuscitation.

PMID- 20158894
TI  - Enhanced late-outgrowth circulating endothelial progenitor cell levels in
      rheumatoid arthritis and correlation with disease activity.
AB  - INTRODUCTION: Angiogenesis and vasculogenesis are critical in rheumatoid
      arthritis (RA) as they could be a key issue for chronic synovitis. Contradictory
      results have been published regarding circulating endothelial progenitor cells
      (EPCs) in RA. We herein investigated late outgrowth EPC sub-population using
      recent recommendations in patients with RA and healthy controls. METHODS: EPCs,
      defined as Lin-/7AAD-/CD34+/CD133+/VEGFR-2+ cells, were quantified by flow
      cytometry in peripheral blood mononuclear cells (PBMCs) from 59 RA patients (mean
      age: 54 +/- 15 years, disease duration: 16 +/- 11 years) and 36 controls (mean
      age: 53 +/- 19 years) free of cardiovascular events and of cardiovascular risk
      factors. Concomitantly, late outgrowth endothelial cell colonies derived from
      culture of PBMCs were analyzed by colony-forming units (CFUs). RESULTS: RA
      patients displayed higher circulating EPC counts than controls (median 112 [27 to
      588] vs. 60 [5 to 275]) per million Lin- mononuclear cells; P = 0.0007). The
      number of circulating EPCs positively correlated with disease activity reflected
      by DAS-28 score (r = 0.43; P = 0.0028) and lower counts were found in RA patients
      fulfilling remission criteria (P = 0.0069). Furthermore, late outgrowth CFU
      number was increased in RA patients compared to controls. In RA, there was no
      association between the number of EPCs and serum markers of inflammation or
      endothelial injury or synovitis. CONCLUSIONS: Our data, based on a well
      characterized definition of late outgrowth EPCs, demonstrate enhanced levels in
      RA and relationship with disease activity. This supports the contribution of
      vasculogenesis in the inflammatory articular process that occurs in RA by
      mobilization of EPCs.

PMID- 20158895
TI  - Real-world car-to-pedestrian-crash data from an urban centre.
AB  - BACKGROUND: Pedestrians are at a high risk for crash and injury. This study aims
      at comparing data from real world crashes with data gathered from experimental
      settings. METHODS: IMPAIR (In-Depth Medical Pedestrian Accident Investigation and
      Reconstruction) was a prospective, observational study performed in a
      metropolitan area. Data was collected on-scene, from clinical records, and
      interviews. Data comprise crash data, details on injury pattern and injury
      severity. RESULTS: Thirty-seven pedestrians (of which 19 males) with a mean 37.1
      years of age were included in the study. The mean collision speed was 49.5 km/h
      (SD 13.7, range, 28 - 93). The mean ISS (31.0, SD 25.4) and the 24% fatality rate
      indicate a substantial trauma load. The most common AIS 4+ injuries were to the
      head (23 subjects), followed by chest (8), pelvis (4), and abdomen (2). An
      association of impact side and injury side (right/left) was found for abdominal,
      chest, pelvic, and upper limb injuries. Primary head impacts were documented on
      the windscreen (19 subjects), hood (10), A-pillar (2), and edge of the car roof
      (2). With bivariate analysis, a significant increase of MAIS 4+ head injury risk
      was found for collision speeds of >40 km/h (OR 9.00, 95% CI 1.96-41.36).
      CONCLUSION: The real-world data from this study is in agreement with previous
      findings from biomechanical models and other simulations. This data suggest that
      there may be reason to include further pedestrian regulations in EuroNCAP.

PMID- 20158896
TI  - General practitioners' perceptions of the effectiveness of medical interventions:
      an exploration of underlying constructs.
AB  - BACKGROUND: Many interventions shown to be effective through clinical trials are
      not readily implemented in clinical practice. Unfortunately, little is known
      regarding how clinicians construct their perceptions of the effectiveness of
      medical interventions. This study aims to explore general practitioners'
      perceptions of the nature of 'effectiveness'. METHODS: The design was qualitative
      in nature using the repertory grid technique to elicit the constructs underlying
      the perceived effectiveness of a range of medical interventions. Eight medical
      interventions were used as stimuli (diclophenac to reduce acute pain, cognitive
      behaviour therapy to treat depression, weight loss surgery to achieve weight
      loss, diet and exercise to prevent type 2 diabetes, statins to prevent heart
      disease, stopping smoking to prevent heart disease, nicotine replacement therapy
      to stop smoking, and stop smoking groups to stop smoking). The setting involved
      face-to-face interviews followed by questionnaires in London Primary Care Trusts.
      Participants included a random sample of 13 general practitioners. RESULTS:
      Analysis of the ratings showed that the constructs clustered around two
      dimensions: low patient effort versus high patient effort (dimension one), and
      small impact versus large impact (dimension two). Dimension one represented
      constructs such as 'success requires little motivation', 'not a lifestyle
      intervention', and 'health-care professional led intervention'. Dimension two
      represented constructs such as 'weak and/or minimal evidence of effectiveness',
      'small treatment effect for users', 'a small proportion of users will benefit'
      and 'not cost-effective'. Constructs within each dimension were closely related.
      CONCLUSIONS: General practitioners judged the effectiveness of medical
      interventions by considering two broad dimensions: the extent to which
      interventions involve patient effort, and the size of their impact. The latter is
      informed by trial evidence, but the patient effort required to achieve
      effectiveness seems to be based on clinical judgement. Some of the failure of
      evidence-based medicine to be implemented may be more explicable if both
      dimensions were attended to.

PMID- 20158897
TI  - The COPE LBP trial: cognitive patient education for low back pain--a cluster
      randomized controlled trial in primary care.
AB  - BACKGROUND: Non-specific low back pain (LBP) is usually self-limiting within 4-6
      weeks. Longstanding pain and disability are not predictable from clinical signs
      or pathoanatomical findings. Pain cognition and physical performance have been
      shown to improve patients with chronic LBP following neurophysiological
      education. The primary aim of this study is to evaluate whether a specific
      cognitive based education programme for patients with LBP in primary care is more
      effective than normal care in terms of increased function. The secondary aims of
      the study are to evaluate whether this intervention also results in earlier
      return to work, decreased pain, increased patient satisfaction, increased quality
      of-life, and cost utility. METHODS/DESIGN: Cluster randomised controlled trial
      with 20 general practitioners and 20 physiotherapists in primary care as the unit
      of randomisation. Each practitioner will recruit up to 10 patients, aged 20 to 55
      years, with non-specific sub-acute/chronic LBP of more than four weeks but less
      than 1 year's duration. Practitioners in the intervention arm will provide
      cognitive patient education intervention in up to four weekly sessions, each
      lasting 30 minutes. Practitioners in the control arm will provide normal
      treatment, but have to make four appointments for the patients. Patients, outcome
      assessors, and study statistician will be blinded to group allocation.
      DISCUSSION: We present the rationale and design of an ongoing RCT study that
      potentially offers an easily implemented treatment strategy for LBP patients in
      primary care. The results will be available in 2012. TRIAL REGISTRATION:
      ISRCTN04323845.

PMID- 20158899
TI  - Electronic search strategies to identify reports of cluster randomized trials in
      MEDLINE: low precision will improve with adherence to reporting standards.
AB  - BACKGROUND: Cluster randomized trials (CRTs) present unique methodological and
      ethical challenges. Researchers conducting systematic reviews of CRTs (e.g.,
      addressing methodological or ethical issues) require efficient electronic search
      strategies (filters or hedges) to identify trials in electronic databases such as
      MEDLINE. According to the CONSORT statement extension to CRTs, the clustered
      design should be clearly identified in titles or abstracts; however, variability
      in terminology may make electronic identification challenging. Our objectives
      were to (a) evaluate sensitivity ("recall") and precision of a well-known
      electronic search strategy ("randomized controlled trial" as publication type)
      with respect to identifying CRTs, (b) evaluate the feasibility of new search
      strategies targeted specifically at CRTs, and (c) determine whether CRTs are
      appropriately identified in titles or abstracts of reports and whether there has
      been improvement over time. METHODS: We manually examined a wide range of health
      journals to identify a gold standard set of CRTs. Search strategies were
      evaluated against the gold standard set, as well as an independent set of CRTs
      included in previous systematic reviews. RESULTS: The existing strategy
      (randomized controlled trial.pt) is sensitive (93.8%) for identifying CRTs, but
      has relatively low precision (9%, number needed to read 11); the number needed to
      read can be halved to 5 (precision 18.4%) by combining with cluster design
      related terms using the Boolean operator AND; combining with the Boolean operator
      OR maximizes sensitivity (99.4%) but would require 28.6 citations read to
      identify one CRT. Only about 50% of CRTs are clearly identified as cluster
      randomized in titles or abstracts; approximately 25% can be identified based on
      the reported units of randomization but are not amenable to electronic searching;
      the remaining 25% cannot be identified except through manual inspection of the
      full-text article. The proportion of trials clearly identified has increased from
      28% between the years 2000-2003, to 60% between 2004-2007 (absolute increase 32%,
      95% CI 17 to 47%). CONCLUSIONS: CRTs should include the phrase "cluster
      randomized trial" in titles or abstracts; this will facilitate more accurate
      indexing of the publication type by reviewers at the National Library of
      Medicine, and efficient textword retrieval of the subset employing cluster
      randomization.

PMID- 20158898
TI  - Lasers, stem cells, and COPD.
AB  - The medical use of low level laser (LLL) irradiation has been occurring for
      decades, primarily in the area of tissue healing and inflammatory conditions.
      Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal
      intervention that has the potential to modulate regenerative processes is worthy
      of attention when searching for novel methods of augmenting stem cell-based
      therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for
      enhancing production of stem cell growth/chemoattractant factors, stimulation of
      angiogenesis, and directly augmenting proliferation of stem cells. The
      combination of LLL together with allogeneic and autologous stem cells, as well as
      post-mobilization directing of stem cells will be discussed.

PMID- 20158900
TI  - Replication of avian, human and swine influenza viruses in porcine respiratory
      explants and association with sialic acid distribution.
AB  - BACKGROUND: Throughout the history of human influenza pandemics, pigs have been
      considered the most likely "mixing vessel" for reassortment between human and
      avian influenza viruses (AIVs). However, the replication efficiencies of
      influenza viruses from various hosts, as well as the expression of sialic acid
      (Sia) receptor variants in the entire porcine respiratory tract have never been
      studied in detail. Therefore, we established porcine nasal, tracheal, bronchial
      and lung explants, which cover the entire porcine respiratory tract with maximal
      similarity to the in vivo situation. Subsequently, we assessed virus yields of
      three porcine, two human and six AIVs in these explants. Since our results on
      virus replication were in disagreement with the previously reported presence of
      putative avian virus receptors in the trachea, we additionally studied the
      distribution of sialic acid receptors by means of lectin histochemistry. Human
      (Sia alpha2-6Gal) and avian virus receptors (Sia alpha2-3Gal) were identified
      with Sambucus Nigra and Maackia amurensis lectins respectively. RESULTS: Compared
      to swine and human influenza viruses, replication of the AIVs was limited in all
      cultures but most strikingly in nasal and tracheal explants. Results of virus
      titrations were confirmed by quantification of infected cells using
      immunohistochemistry. By lectin histochemistry we found moderate to abundant
      expression of the human-like virus receptors in all explant systems but minimal
      binding of the lectins that identify avian-like receptors, especially in the
      nasal, tracheal and bronchial epithelium. CONCLUSIONS: The species barrier that
      restricts the transmission of influenza viruses from one host to another remains
      preserved in our porcine respiratory explants. Therefore this system offers a
      valuable alternative to study virus and/or host properties required for
      adaptation or reassortment of influenza viruses. Our results indicate that, based
      on the expression of Sia receptors alone, the pig is unlikely to be a more
      appropriate mixing vessel for influenza viruses than humans. We conclude that too
      little is known on the exact mechanism and on predisposing factors for
      reassortment to assess the true role of the pig in the emergence of novel
      influenza viruses.

PMID- 20158901
TI  - Analysis of chick (Gallus gallus) middle ear columella formation.
AB  - BACKGROUND: The chick middle ear bone, the columella, provides an accessible
      model in which to study the tissue and molecular interactions necessary for
      induction and patterning of the columella, as well as associated multiple aspects
      of endochondral ossification. These include mesenchymal condensation,
      chondrogenesis, ossification of the medial footplate and shaft, and joint
      formation between the persistent cartilage of the extracolumella and ossified
      columella. Middle and external ear defects are responsible for approximately 10%
      of congenital hearing defects. Thus, understanding the morphogenesis and the
      molecular mechanisms of the formation of the middle ear is important to
      understanding normal and abnormal development of this essential component of the
      hearing apparatus. RESULTS: The columella, which arises from proximal
      ectomesenchyme of the second pharyngeal arch, is induced and patterned in a
      dynamic multi-step process. From the footplate, which inserts into the inner ear
      oval window, the shaft spans the pneumatic middle ear cavity, and the
      extracolumella inserts into the tympanic membrane. Through marker gene and
      immunolabeling analysis, we have determined the onset of each stage in the
      columella's development, from condensation to ossification. Significantly, a
      single condensation with the putative shaft and extracolumella arms already
      distinguishable is observed shortly before initiation of five separate
      chondrogenic centers within these structures. Ossification begins later, with
      periosteum formation in the shaft and, unexpectedly, a separate periosteum in the
      footplate. CONCLUSIONS: The data presented in this study document the
      spatiotemporal events leading to morphogenesis of the columella and middle ear
      structures and provide the first gene expression data for this region. These data
      identify candidate genes and facilitate future functional studies and elucidation
      of the molecular mechanisms of columella formation.

PMID- 20158902
TI  - Basophil sensitivity through CD63 or CD203c is a functional measure for specific
      immunotherapy.
AB  - BACKGROUND: Subcutaneous Immunotherapy (SCIT) modifies the allergic response and
      relieves allergic symptoms. SCIT is the only and a very effective treatment for
      insect venom allergy. We hypothesized that basophil sensitivity, measured through
      the basophil activation test, would decrease during SCIT up dosing. Expression of
      CD203c was compared to CD63 as marker for basophil activation, using a Bland
      Altman plot and ROC curves. METHODS: Patients (n = 18) starting subcutaneous SCIT
      for wasp allergy with an up dosing scheme of 7 to 11 weeks were enrolled.
      Heparinised blood samples were drawn at weeks 1-4, 7 and at the first maintenance
      visit. Basophils were stimulated at 7 log dilutions of V. vespula allergen for 15
      min, and were stained with CD203c and CD63. Basophils were identified as CD203c+
      leukocytes, and the proportion of CD63+ and CD203c+ cells were plotted against
      allergen concentration. A sigmoid curve was fitted to the points, and the
      allergen concentration at which half of the maximal activation was achieved,
      LC50, was calculated. In another series of experiments, LC50 calculated in whole
      blood (AP) was subtracted from LC50 calculated with basophils suspended in plasma
      from a nonatopic donor (HS) to determine the protective effect of soluble factors
      in blood of patients treated with SCIT. RESULTS: Heparin blood basophil
      activation was similar through CD63 and CD203c. Basophils were significantly more
      sensitized three weeks after initiation of SCIT compared to baseline (p < 0,01).
      The difference in LC50 increased by 1,04 LC50 units (p = 0,04) in patients that
      had just achieved maintenance dose compared with patients before initiating SCIT.
      When maintenance allergen concentrations had been reached, an increase in the
      protective plasma component was documented. Blood basophil concentration was
      marginally reduced by SCIT. CONCLUSION: Basophil activation is a versatile and
      sensitive tool that measures changes in the humoral immune response to allergen
      during SCIT.

PMID- 20158903
TI  - Laxative activities of Mareya micrantha (Benth.) Mull. Arg. (Euphorbiaceae) leaf
      aqueous extract in rats.
AB  - BACKGROUND: Mareya micrantha (Benth.) Mull. Arg. (Euphorbiaceae) is a shrub that
      is commonly used in Cote d'Ivoire (West Africa) for the treatment of constipation
      and as an ocytocic drug. The present study was carried out to investigate the
      laxative activity of Mareya micrantha in albino's Wistar rats. METHODS: Rats were
      divided in 5 groups of 5 animals each, first group as control, second group
      served as standard (sodium picosulfate) while group 3, 4 and 5 were treated with
      leaf aqueous extract of Mareya micrantha at doses of 100, 200 and 400 mg/kg body
      weight (b.w.), per os respectively. The laxative activity was determined based on
      the weight of the faeces matter. The effects of the leaves aqueous extract of
      Mareya micrantha and castor oil were also evaluated on intestinal transit,
      intestinal fluid accumulation and ions secretion. RESULTS: Phytochemicals
      screening of the extract revealed the presence of flavonoids, alkaloids, tannins,
      polyphenols, sterols and polyterpenes. The aqueous extract of Mareya micrantha
      applied orally (100, 200 and 400 mg/kg; p.o.), produced significant laxative
      activity and reduced loperamide induced constipation in dose dependant manner.
      The effect of the extract at 200 and 400 mg/kg (p.o.) was similar to that of
      reference drug sodium picosulfate (5 mg/kg, p.o). The same doses of the extract
      (200 and 400 mg/kg, p.o.) produced a significant increase (p < 0.01) of
      intestinal transit in comparison with castor oil (2 mL) (p < 0.01). Moreover, the
      extract induced a significant enteropooling and excretion of Cl-, Na+, K+ and
      Ca2+ in the intestinal fluid (p < 0.01). CONCLUSIONS: The results showed that the
      aqueous extract of Mareya micrantha has a significant laxative activity and
      supports its traditional use in herbal medicine.

PMID- 20158904
TI  - sCD4-17b bifunctional protein: extremely broad and potent neutralization of HIV-1
      Env pseudotyped viruses from genetically diverse primary isolates.
AB  - BACKGROUND: We previously described a potent recombinant HIV-1 neutralizing
      protein, sCD4-17b, composed of soluble CD4 attached via a flexible polypeptide
      linker to an SCFv of the 17b human monoclonal antibody directed against the
      highly conserved CD4-induced bridging sheet of gp120 involved in coreceptor
      binding. The sCD4 moiety of the bifunctional protein binds to gp120 on free
      virions, thereby enabling the 17b SCFv moiety to bind and block the
      gp120/coreceptor interaction required for entry. The previous studies using the
      MAGI-CCR5 assay system indicated that sCD4-17b (in concentrated cell culture
      medium, or partially purified) potently neutralized several genetically diverse
      HIIV-1 primary isolates; however, at the concentrations tested it was ineffective
      against several other strains despite the conservation of binding sites for both
      CD4 and 17b. To address this puzzle, we designed variants of sCD4-17b with
      different linker lengths, and tested the neutralizing activities of the
      immunoaffinity purified proteins over a broader concentration range against a
      large number of genetically diverse HIV-1 primary isolates, using the TZM-bl Env
      pseudotype assay system. We also examined the sCD4-17b sensitivities of isogenic
      viruses generated from different producer cell types. RESULTS: We observed that
      immunoaffinity purified sCD4-17b effectively neutralized HIV-1 pseudotypes,
      including those from HIV-1 isolates previously found to be relatively insensitive
      in the MAGI-CCR5 assay. The potencies were equivalent for the original construct
      and a variant with a longer linker, as observed with both pseudotype particles
      and infectious virions; by contrast, a construct with a linker too short to
      enable simultaneous binding of the sCD4 and 17b SCFv moieties was much less
      effective. sCD4-17b displayed potent neutralizing activity against 100% of nearly
      4 dozen HIV-1 primary isolates from diverse genetic subtypes (clades A, B, C, D,
      F, and circulating recombinant forms AE and AG). The neutralization breadth and
      potency were superior to what have been reported for the broadly neutralizing
      monoclonal antibodies IgG b12, 2G12, 2F5, and 4E10. The activity of sCD4-17b was
      found to be similar against isogenic virus particles from infectious molecular
      clones derived either directly from the transfected producer cell line or after a
      single passage through PBMCs; this contrasted with the monoclonal antibodies,
      which were less potent against the PMBC-passaged viruses. CONCLUSIONS: The
      results highlight the extremely potent and broad neutralizing activity of sCD4
      17b against genetically diverse HIV-1 primary isolates. The bifunctional protein
      has potential applications for antiviral approaches to combat HIV infection.

PMID- 20158905
TI  - Protein microarray: sensitive and effective immunodetection for drug residues.
AB  - BACKGROUND: Veterinary drugs such as clenbuterol (CL) and sulfamethazine (SM2)
      are low molecular weight (<1000 Da) compounds, or haptens, that are difficult to
      develop immunoassays due to their low immunogenicity. In this study, we
      conjugated the drugs to ovalbumin to increase their immunogenicity for antiserum
      production in rabbits and developed a protein microarray immunoassay for
      detection of clenbuterol and sulfamethazine. The sensitivity of this approach was
      then compared to traditional ELISA technique. RESULTS: The artificial antigens
      were spotted on microarray slides. Standard concentrations of the compounds were
      added to compete with the spotted antigens for binding to the antisera to
      determine the IC50. Our microarray assay showed the IC50 were 39.6 ng/ml for CL
      and 48.8 ng/ml for SM2, while the traditional competitive indirect-ELISA (ci
      ELISA) showed the IC50 were 190.7 ng/ml for CL and 156.7 ng/ml for SM2. We
      further validated the two methods with CL fortified chicken muscle tissues, and
      the protein microarray assay showed 90% recovery while the ci-ELISA had 76%
      recovery rate. When tested with CL-fed chicken muscle tissues, the protein
      microarray assay had higher sensitivity (0.9 ng/g) than the ci-ELISA (0.1 ng/g)
      for detection of CL residues. CONCLUSIONS: The protein microarrays showed 4.5 and
      3.5 times lower IC50 than the ci-ELISA detection for CL and SM2, respectively,
      suggesting that immunodetection of small molecules with protein microarray is a
      better approach than the traditional ELISA technique.

PMID- 20158906
TI  - In situ detection of Gag-specific CD8+ cells in the GI tract of SIV infected
      Rhesus macaques.
AB  - BACKGROUND: SIV and HIV predominantly replicate in lymphoid tissue, but the study
      of virus specific CD8+ T cells in intact lymphoid tissue is difficult, as
      traditional in situ tetramer staining requires fresh tissue. RESULTS: In this
      report, we demonstrate a novel technique using Qdot 655-conjugated peptide-MHC
      multimers to directly visualize SIV specific cells in cryopreserved tissue
      biopsies from chronically SIVmac239 infected Rhesus macaques. Qdot 655 multimers
      showed similar sensitivity and specificity to APC-conjugated tetramers by flow
      cytometry analysis, but yielded ten-fold higher signal intensity when imaged by
      fluorescence microscopy. Using this technique, we detected CD8+ T cells which
      recognize an immunodominant epitope (Gag CM9) in the spleen, lymph nodes, ileum
      and colon. In all these tissues, the Gag CM9 positive cells were mainly located
      in the extra follicular T cell zone. In the ileum and colon, we found Gag CM9
      positive cells concentrated in Peyer's patches and solitary lymphoid follicles, a
      pattern of localization not previously described. CONCLUSIONS: The use of Qdot
      multimers provide an anatomic and quantitative evaluation of SIV specific CD8+ T
      cell responses in SIV pathogenesis, and may prove useful to studies of SIV
      specific CD8+ T cell responses elicited by vaccines and other immunotherapies in
      the non-human primate model.

PMID- 20158907
TI  - In-depth sequencing of the siRNAs associated with peach latent mosaic viroid
      infection.
AB  - BACKGROUND: It has been observed that following viroid infection, there is an
      accumulation of viroid-derived siRNAs in infected plants. Some experimental
      results suggest that these small RNAs may be produced by the plant defense system
      to protect it from infection, indicating that viroids can elicit the RNA
      silencing pathways. The objective of this study is to identify in the peach
      latent mosaic viroid (PLMVd), a model RNA genome, the regions that are most
      susceptible to RNA interference machinery. RESULTS: The RNA isolated from an
      infected tree have been used to sequence in parallel viroid species and small non
      coding RNA species. Specifically, PLMVd RNAs were amplified, cloned and sequenced
      according to a conventional approach, while small non-coding RNAs were determined
      by high-throughput sequencing. The first led to the typing of 18 novel PLMVd
      variants. The second provided a library of small RNAs including 880 000 sequences
      corresponding to PLMVd-derived siRNAs, which makes up 11.2% of the sequences of
      the infected library. These siRNAs contain mainly 21-22 nucleotide RNAs and are
      equivalently distributed between the plus and the minus polarities of the viroid.
      They cover the complete viroid genome, although the amount varies depending on
      the regions. These regions do not necessarily correlate with the double-stranded
      requirement to be a substrate for Dicer-like enzymes. We noted that some
      sequences encompass the hammerhead self-cleavage site, indicating that the
      circular conformers could be processed by the RNA-silencing machinery. Finally, a
      bias in the relative abundance of the nature of the 5' nucleotides was observed
      (A, U >> G, C). CONCLUSIONS: The approach used provided us a quantitative
      representation of the PLMVd-derived siRNAs retrieved from infected peach trees.
      These siRNAs account for a relatively large proportion of the small non-coding
      RNAs. Surprisingly, the siRNAs from some regions of the PLMVd genome appear over
      represented, although these regions are not necessarily forming sufficiently long
      double-stranded structures to satisfy Dicer-like criteria for substrate
      specificity. Importantly, this large library of siRNAs gave several hints as to
      the components of the involved silencing machinery.

PMID- 20158908
TI  - Pretest expectations strongly influence interpretation of abnormal laboratory
      results and further management.
AB  - BACKGROUND: Abnormal results of diagnostic laboratory tests can be difficult to
      interpret when disease probability is very low. Although most physicians
      generally do not use Bayesian calculations to interpret abnormal results, their
      estimates of pretest disease probability and reasons for ordering diagnostic
      tests may--in a more implicit manner--influence test interpretation and further
      management. A better understanding of this influence may help to improve test
      interpretation and management. Therefore, the objective of this study was to
      examine the influence of physicians' pretest disease probability estimates, and
      their reasons for ordering diagnostic tests, on test result interpretation,
      posttest probability estimates and further management. METHODS: Prospective study
      among 87 primary care physicians in the Netherlands who each ordered laboratory
      tests for 25 patients. They recorded their reasons for ordering the tests (to
      exclude or confirm disease or to reassure patients) and their pretest disease
      probability estimates. Upon receiving the results they recorded how they
      interpreted the tests, their posttest probability estimates and further
      management. Logistic regression was used to analyse whether the pretest
      probability and the reasons for ordering tests influenced the interpretation, the
      posttest probability estimates and the decisions on further management. RESULTS:
      The physicians ordered tests for diagnostic purposes for 1253 patients; 742
      patients had an abnormal result (64%). Physicians' pretest probability estimates
      and their reasons for ordering diagnostic tests influenced test interpretation,
      posttest probability estimates and further management. Abnormal results of tests
      ordered for reasons of reassurance were significantly more likely to be
      interpreted as normal (65.8%) compared to tests ordered to confirm a diagnosis or
      exclude a disease (27.7% and 50.9%, respectively). The odds for abnormal results
      to be interpreted as normal were much lower when the physician estimated a high
      pretest disease probability, compared to a low pretest probability estimate (OR =
      0.18, 95% CI = 0.07-0.52, p < 0.001). CONCLUSIONS: Interpretation and management
      of abnormal test results were strongly influenced by physicians' estimation of
      pretest disease probability and by the reason for ordering the test. By relating
      abnormal laboratory results to their pretest expectations, physicians may seek a
      balance between over- and under-reacting to laboratory test results.

PMID- 20158909
TI  - Characterization of two diesel fuel degrading microbial consortia enriched from a
      non acclimated, complex source of microorganisms.
AB  - BACKGROUND: The bioremediation of soils impacted by diesel fuels is very often
      limited by the lack of indigenous microflora with the required broad substrate
      specificity. In such cases, the soil inoculation with cultures with the desired
      catabolic capabilities (bioaugmentation) is an essential option. The use of
      consortia of microorganisms obtained from rich sources of microbes (e.g.,
      sludges, composts, manure) via enrichment (i.e., serial growth transfers) on the
      polluting hydrocarbons would provide bioremediation enhancements more robust and
      reproducible than those achieved with specialized pure cultures or tailored
      combinations (co-cultures) of them, together with none or minor risks of soil
      loading with unrelated or pathogenic allocthonous microorganisms. RESULTS: In
      this work, two microbial consortia, i.e., ENZ-G1 and ENZ-G2, were enriched from
      ENZYVEBA (a complex commercial source of microorganisms) on Diesel (G1) and HiQ
      Diesel (G2), respectively, and characterized in terms of microbial composition
      and hydrocarbon biodegradation capability and specificity. ENZ-G1 and ENZ-G2
      exhibited a comparable and remarkable biodegradation capability and specificity
      towards n-C10 to n-C24 linear paraffins by removing about 90% of 1 g l-1 of
      diesel fuel applied after 10 days of aerobic shaken flask batch culture
      incubation at 30 degrees C. Cultivation dependent and independent approaches
      evidenced that both consortia consist of bacteria belonging to the genera
      Chryseobacterium, Acinetobacter, Psudomonas, Stenotrophomonas, Alcaligenes and
      Gordonia along with the fungus Trametes gibbosa. However, only the fungus was
      found to grow and remarkably biodegrade G1 and G2 hydrocarbons under the same
      conditions. The biodegradation activity and specificity and the microbial
      composition of ENZ-G1 and ENZ-G2 did not significantly change after
      cryopreservation and storage at -20 degrees C for several months. CONCLUSIONS:
      ENZ-G1 and ENZ-G2 are very similar highly enriched consortia of bacteria and a
      fungus capable of extensively degrading a broad range of the hydrocarbons mainly
      composing diesel fuels. Given their remarkable biodegradation potential,
      stability and resistance to cryopreservation, both consortia appear very
      interesting candidates for bioaugmentation operations on Diesel fuel impacted
      soils and sites.

PMID- 20158910
TI  - Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma
      biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy
      subjects.
AB  - BACKGROUND: CVD in obesity and T2DM are associated with endothelial activation,
      elevated plasma vascular inflammation markers and a prothrombotic state. We
      examined the contribution of FFA to these abnormalities following a 48-hour
      physiological increase in plasma FFA to levels of obesity and diabetes in a group
      of healthy subjects. METHODS: 40 non-diabetic subjects (age = 38 +/- 3 yr, BMI =
      28 +/- 1 kg/m2, FPG = 95 +/- 1 mg/dl, HbA1c = 5.3 +/- 0.1%) were admitted twice
      and received a 48-hour infusion of normal saline or low-dose lipid. Plasma was
      drawn for intracellular (ICAM-1) and vascular (VCAM-1) adhesion molecules-1, E
      selectin (sE-S), myeloperoxidase (MPO) and total plasminogen inhibitor-1 (tPAI
      1). Insulin sensitivity was measured by a hyperglycemic clamp (M/I). RESULTS:
      Lipid infusion increased plasma FFA to levels observed in obesity and T2DM and
      reduced insulin sensitivity by 27% (p = 0.01). Elevated plasma FFA increased
      plasma markers of endothelial activation ICAM-1 (138 +/- 10 vs. 186 +/- 25
      ng/ml), VCAM-1 (1066 +/- 67 vs. 1204 +/- 65 ng/ml) and sE-S (20 +/- 1 vs. 24 +/-
      1 ng/ml) between 13-35% and by > or = 2-fold plasma levels of myeloperoxidase
      (7.5 +/- 0.9 to 15 +/- 25 ng/ml), an inflammatory marker of future CVD, and tPAI
      1 (9.7 +/- 0.6 to 22.5 +/- 1.5 ng/ml), an indicator of a prothrombotic state (all
      p < or = 0.01). The FFA-induced increase was independent from the degree of
      adiposity, being of similar magnitude in lean, overweight and obese subjects.
      CONCLUSIONS: An increase in plasma FFA within the physiological range observed in
      obesity and T2DM induces markers of endothelial activation, vascular inflammation
      and thrombosis in healthy subjects. This suggests that even transient (48-hour)
      and modest increases in plasma FFA may initiate early vascular abnormalities that
      promote atherosclerosis and CVD.

PMID- 20158911
TI  - Generation and characterization of a Tet-On (rtTA-M2) transgenic rat.
AB  - BACKGROUND: The tetracycline-inducible gene regulation system is a powerful tool
      that allows temporal and dose-dependent regulation of target transgene expression
      in vitro and in vivo. Several tetracycline-inducible transgenic mouse models have
      been described with ubiquitous or tissue-specific expression of tetracycline
      transactivator (tTA), reverse tetracycline-transactivator (rtTA) or Tet repressor
      (TetR). Here we describe a Tet-On transgenic rat that ubiquitously expresses rtTA
      M2 driven by the murine ROSA 26 promoter. RESULTS: The homozygous rat line (ROSA
      rtTA-M2) generated by lentiviral vector injection, has a single integration site
      and was derived from the offspring of a genetic mosaic founder with multiple
      transgene integrations. The rtTA-M2 transgene integrated into an intron of a
      putative gene on chromosome 2 and does not appear to affect the tissue
      specificity or expression of that gene. Fibroblasts from the ROSA-rtTA-M2 rats
      were transduced with a TetO7/CMV-EGFP lentivirus and exhibited doxycycline dose
      dependent expression of the EGFP reporter transgene, in vitro. In addition,
      doxycycline-inducible EGFP expression was observed, in vivo, when the TetO7/CMV
      EGFP lentivirus was injected into testis, kidney and muscle tissues of ROSA-rtTA
      M2 rats. CONCLUSIONS: This conditional expression rat model may have application
      for transgenic overexpression or knockdown studies of gene function in
      development, disease and gene therapy.

PMID- 20158912
TI  - Plasma levels of surfactant protein D and KL-6 for evaluation of lung injury in
      critically ill mechanically ventilated patients.
AB  - BACKGROUND: Preventing ventilator-associated lung injury (VALI) has become
      pivotal in mechanical ventilation of patients with acute lung injury (ALI) or its
      more severe form, acute respiratory distress syndrome (ARDS). In the present
      study we investigated whether plasma levels of lung-specific biological markers
      can be used to evaluate lung injury in patients with ALI/ARDS and patients
      without lung injury at onset of mechanical ventilation. METHODS: Plasma levels of
      surfactant protein D (SP-D), Clara Cell protein (CC16), KL-6 and soluble receptor
      for advanced glycation end-products (sRAGE) were measured in plasma samples
      obtained from 36 patients - 16 patients who were intubated and mechanically
      ventilated because of ALI/ARDS and 20 patients without lung injury at the onset
      of mechanical ventilation and during conduct of the study. Patients were
      ventilated with either a lung-protective strategy using lower tidal volumes or a
      potentially injurious strategy using conventional tidal volumes. Levels of
      biological markers were measured retrospectively at baseline and after 2 days of
      mechanical ventilation. RESULTS: Plasma levels of CC16 and KL-6 were higher in
      ALI/ARDS patients at baseline as compared to patients without lung injury. SP-D
      and sRAGE levels were not significantly different between these patients. In
      ALI/ARDS patients, SP-D and KL-6 levels increased over time, which was attenuated
      by lung-protective mechanical ventilation using lower tidal volumes (P = 0.02 for
      both biological markers). In these patients, with either ventilation strategy no
      changes over time were observed for plasma levels of CC16 and sRAGE. In patients
      without lung injury, no changes of plasma levels of any of the measured
      biological markers were observed. CONCLUSION: Plasma levels of SP-D and KL-6 rise
      with potentially injurious ventilator settings, and thus may serve as biological
      markers of VALI in patients with ALI/ARDS.

PMID- 20158913
TI  - Neoadjuvant multidrug chemotherapy including high-dose methotrexate modifies VEGF
      expression in osteosarcoma: an immunohistochemical analysis.
AB  - BACKGROUND: Angiogenesis plays a role in the progression of osteosarcoma, as well
      as in other mesenchymal tumors and carcinomas, and it is most commonly assessed
      by vascular endothelial growth factor (VEGF) expression or tumor CD31-positive
      microvessel density (MVD). Tumor VEGF expression is predictive of poor prognosis,
      and chemotherapy can affect the selection of angiogenic pattern. The aim of the
      study was to investigate the clinical and prognostic significance of VEGF and
      CD31 in osteosarcoma, both at diagnosis and after neoadjuvant chemotherapy, in
      order to identify a potential role of chemotherapy in angiogenic phenotype.
      METHODS: A retrospective analysis was performed on 16 patients with high grade
      osteosarcoma. In each case archival pre-treatment biopsy tissue and post
      chemotherapy tumor specimens were immunohistochemically stained against CD31 and
      VEGF, as markers of angiogenic proliferation both in newly diagnosed primary
      osteosarcoma and after multidrug chemotherapy including high-dose methotrexate
      (HDMTX). The correlation between clinicopathological parameters and the degree of
      tumor VEGF and CD31 expression was statistically assessed using the chi(2) test
      verified with Yates' test for comparison of two groups. Significance was set at p
      < 0.05. RESULTS: Expression of VEGF was positive in 11 cases/16 of cases at
      diagnosis. Moreover, 8 cases/16 untreated osteosarcomas were CD31-negative, but
      the other 8 showed an high expression of CD31. VEGF expression in viable tumor
      cells after neoadjuvant chemotherapy was observed in all cases; in particular,
      there was an increased VEGF expression (post-chemotherapy VEGF--biopsy VEGF) in
      11 cases/16. CD31 expression increased in 11 cases/16 and decreased in 3 cases
      after chemotherapy. The data relating to the change in staining following
      chemotherapy appear statistically significant for VEGF expression (p < 0.05), but
      not for CD31 (p > 0.05). CONCLUSIONS: Even if the study included few patients,
      these results confirm that VEGF and CD31 expression is affected by multidrug
      chemotherapy including HDMTX. The expression of angiogenic factors that increase
      microvessel density (MVD) can contribute to the penetration of chemotherapeutic
      drugs into the tumor in the adjuvant stage of treatment. So VEGF could have a
      paradoxical effect: it is associated with a poor outcome but it could be a
      potential target for anti-angiogenic therapy.

PMID- 20158915
TI  - In-vivo transfection of pcDNA3.1-IGFBP7 inhibits melanoma growth in mice through
      apoptosis induction and VEGF downexpression.
AB  - BACKGROUND: Genome-wide RNA interference screening study revealed that loss of
      expression of insulin-like growth factor binding protein 7 (IGFBP7) is a critical
      step in development of a malignant melanoma (MM), and this secreted protein plays
      a central role in apoptosis of MM. In this study we constructed pcDNA3.1-IGFBP7
      to obtain high expression of IGBPF7 and to inhibit the growth of MM in C57BL/6J
      mice. METHODS: pcDNA3.1-IGFBP7 was transfected into B16-F10 cell, the expression
      of IGFBP7 was detected by RT-PCR and western blot. The proliferations and
      apoptosis rates of transfected and control cells were measured by CCK8 and FCM,
      respectively. The tumorigenicity and tumor growth in both pcDNA3.1-IGFBP7 group
      and control groups were studied in C57BL/6J mice model. IGFBP7, caspase-3, and
      VEGF expressions in tumor tissue were measured by immunohistochemistry. Apoptosis
      of tumors were detected by TUNEL. RESULTS: We demonstrated this plasmid inhibited
      proliferation of B16-F10 melanoma cells efficiently in vivo, exploiting the high
      expression of IGFBP7. More importantly, in-vivo transfection of pcDNA3.1-IGFBP7
      inhibited MM growth in C57BL/6J mice. The inhibition of MM growth was proved
      owing to apoptosis and reduced expression of VEGF induced by pcDNA3.1-IGFBP7.
      CONCLUSIONS: These results suggest a potential new clinical strategy for MM gene
      treatment.

PMID- 20158914
TI  - Insertional mutagenesis enables cleistothecial formation in a non-mating strain
      of Histoplasma capsulatum.
AB  - BACKGROUND: Histoplasma capsulatum is a pathogenic ascomycete fungus that rapidly
      loses mating ability in culture. Loss of mating ability, as well as the
      organism's low rate of targeted gene replacement, limits techniques available for
      genetic studies in H. capsulatum. Understanding molecular mechanisms regulating
      mating in this organism may allow us to reverse or prevent loss of mating in H.
      capsulatum strains, introducing a variety of classical genetics techniques to the
      field. We generated a strain, UC1, by insertional mutagenesis of the laboratory
      strain G217B, and found that UC1 acquired the ability to form mating structures
      called cleistothecia. The aim of this study was to determine the mechanism by
      which UC1 gained the ability to form cleistothecia. We also present initial
      studies demonstrating that UC1 can be used as a tool to determine molecular
      correlates of mating in H. capsulatum. RESULTS: The strain UC1 was found to have
      increased RNA levels of the mating locus transcription factor (MAT1-1-1), and the
      putative alpha pheromone (PPG1) compared to G217B. Agrobacterium-mediated
      transformation and integration of T-DNA from the vector pCB301-GFP-HYG were found
      to be partially responsible for the increased RNA levels of these genes; however,
      the site of integration appeared to play the largest role in the strain's ability
      to form cleistothecia. Silencing HMK1, a putative FUS3/KSS1 homolog, had no
      effect on cleistothecial production by UC1. Protein kinase C (PKC1) RNA and
      protein levels were increased in UC1 compared to G217B, and pheromone production
      was found to be linked with Pkc1 activity in H. capsulatum. CONCLUSIONS: The site
      of the T-DNA integration event appears to play the largest role in UC1's ability
      to form cleistothecia. We show that the UC1 strain can be used as a tool to study
      cleistothecia production in H. capsulatum by manipulating the strain, or by
      identifying differences between UC1 and G217B. Using these approaches, we were
      able to link Pkc1 activity with pheromone production in H. capsulatum; however,
      further studies are required to determine molecular mechanisms behind this. These
      studies may reveal regulatory mechanisms that can be manipulated to restore
      mating ability in H. capsulatum laboratory strains.

PMID- 20158916
TI  - Evolution of plant RNA polymerase IV/V genes: evidence of subneofunctionalization
      of duplicated NRPD2/NRPE2-like paralogs in Viola (Violaceae).
AB  - BACKGROUND: DNA-dependent RNA polymerase IV and V (Pol IV and V) are multi
      subunit enzymes occurring in plants. The origin of Pol V, specific to
      angiosperms, from Pol IV, which is present in all land plants, is linked to the
      duplication of the gene encoding the largest subunit and the subsequent
      subneofunctionalization of the two paralogs (NRPD1 and NRPE1). Additional
      duplication of the second-largest subunit, NRPD2/NRPE2, has happened
      independently in at least some eudicot lineages, but its paralogs are often
      subject to concerted evolution and gene death and little is known about their
      evolution nor their affinity with Pol IV and Pol V. RESULTS: We sequenced a
      approximately 1500 bp NRPD2/E2-like fragment from 18 Viola species, mostly
      paleopolyploids, and 6 non-Viola Violaceae species. Incongruence between the
      NRPD2/E2-like gene phylogeny and species phylogeny indicates a first duplication
      of NRPD2 relatively basally in Violaceae, with subsequent sorting of paralogs in
      the descendants, followed by a second duplication in the common ancestor of Viola
      and Allexis. In Viola, the mutation pattern suggested (sub-) neofunctionalization
      of the two NRPD2/E2-like paralogs, NRPD2/E2-a and NRPD2/E2-b. The dN/dS ratios
      indicated that a 54 bp region exerted strong positive selection for both paralogs
      immediately following duplication. This 54 bp region encodes a domain that is
      involved in the binding of the Nrpd2 subunit with other Pol IV/V subunits, and
      may be important for correct recognition of subunits specific to Pol IV and Pol
      V. Across all Viola taxa 73 NRPD2/E2-like sequences were obtained, of which 23
      (32%) were putative pseudogenes - all occurring in polyploids. The NRPD2
      duplication was conserved in all lineages except the diploid MELVIO clade, in
      which NRPD2/E2-b was lost, and its allopolyploid derivates from hybridization
      with the CHAM clade, section Viola and section Melanium, in which NRPD2/E2-a
      occurred in multiple copies while NRPD2/E2-b paralogs were either absent or
      pseudogenized. CONCLUSIONS: Following the relatively recent split of Pol IV and
      Pol V, our data indicate that these two multi-subunit enzymes are still in the
      process of specialization and each acquiring fully subfunctionalized copies of
      their subunit genes. Even after specialization, the NRPD2/E2-like paralogs are
      prone to pseudogenization and gene conversion and NRPD2 and NRPE2 copy number is
      a highly dynamic process modulated by allopolyploidy and gene death.

PMID- 20158917
TI  - Identification of candidates for cyclotide biosynthesis and cyclisation by
      expressed sequence tag analysis of Oldenlandia affinis.
AB  - BACKGROUND: Cyclotides are a family of circular peptides that exhibit a range of
      biological activities, including anti-bacterial, cytotoxic, anti-HIV activities,
      and are proposed to function in plant defence. Their high stability has motivated
      their development as scaffolds for the stabilisation of peptide drugs.
      Oldenlandia affinis is a member of the Rubiaceae (coffee) family from which 18
      cyclotides have been sequenced to date, but the details of their processing from
      precursor proteins have only begun to be elucidated. To increase the speed at
      which genes involved in cyclotide biosynthesis and processing are being
      discovered, an expressed sequence tag (EST) project was initiated to survey the
      transcript profile of O. affinis and to propose some future directions of
      research on in vivo protein cyclisation. RESULTS: Using flow cytometry the
      holoploid genome size (1C-value) of O. affinis was estimated to be 4,210 - 4,284
      Mbp, one of the largest genomes of the Rubiaceae family. High-quality ESTs were
      identified, 1,117 in total, from leaf cDNAs and assembled into 502 contigs,
      comprising 202 consensus sequences and 300 singletons. ESTs encoding the
      cyclotide precursors for kalata B1 (Oak1) and kalata B2 (Oak4) were among the 20
      most abundant ESTs. In total, 31 ESTs encoded cyclotide precursors, representing
      a distinct commitment of 2.8% of the O. affinis transcriptome to cyclotide
      biosynthesis. The high expression levels of cyclotide precursor transcripts are
      consistent with the abundance of mature cyclic peptides in O. affinis. A new
      cyclotide precursor named Oak5 was isolated and represents the first cDNA for the
      bracelet class of cyclotides in O. affinis. Clones encoding enzymes potentially
      involved in processing cyclotides were also identified and include enzymes
      involved in oxidative folding and proteolytic processing. CONCLUSION: The EST
      library generated in this study provides a valuable resource for the study of the
      cyclisation of plant peptides. Further analysis of the candidates for cyclotide
      processing discovered in this work will increase our understanding and aid in
      reconstructing cyclotide production using transgenic systems and will benefit
      their development in pharmaceutical applications and insect-resistant crop
      plants.

PMID- 20158918
TI  - Incentive payments to general practitioners aimed at increasing opportunistic
      testing of young women for chlamydia: a pilot cluster randomised controlled
      trial.
AB  - BACKGROUND: Financial incentives have been used for many years internationally to
      improve quality of care in general practice. The aim of this pilot study was to
      determine if offering general practitioners (GP) a small incentive payment per
      test would increase chlamydia testing in women aged 16 to 24 years, attending
      general practice. METHODS: General practice clinics (n = 12) across Victoria,
      Australia, were cluster randomized to receive either a $AUD5 payment per
      chlamydia test or no payment for testing 16 to 24 year old women for chlamydia.
      Data were collected on the number of chlamydia tests and patient consultations
      undertaken by each GP over two time periods: 12 month pre-trial and 6 month trial
      period. The impact of the intervention was assessed using a mixed effects
      logistic regression model, accommodating for clustering at GP level. RESULTS:
      Testing increased from 6.2% (95% CI: 4.2, 8.4) to 8.8% (95% CI: 4.8, 13.0) (p =
      0.1) in the control group and from 11.5% (95% CI: 4.6, 18.5) to 13.4% (95% CI:
      9.5, 17.5) (p = 0.4) in the intervention group. Overall, the intervention did not
      result in a significant increase in chlamydia testing in general practice. The
      odds ratio for an increase in testing in the intervention group compared to the
      control group was 0.9 (95% CI: 0.6, 1.2). Major barriers to increased chlamydia
      testing reported by GPs included a lack of time, difficulty in remembering to
      offer testing and a lack of patient awareness around testing. CONCLUSIONS: A
      small financial incentive alone did not increase chlamydia testing among young
      women attending general practice. It is possible small incentive payments in
      conjunction with reminder and feedback systems may be effective, as may higher
      financial incentive payments. Further research is required to determine if
      financial incentives can increase testing in Australian general practice, the
      type and level of financial scheme required and whether incentives needs to be
      part of a multi-faceted package. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trial Registry ACTRN12608000499381.

PMID- 20158919
TI  - HDAPD: a web tool for searching the disease-associated protein structures.
AB  - BACKGROUND: The protein structures of the disease-associated proteins are
      important for proceeding with the structure-based drug design to against a
      particular disease. Up until now, proteins structures are usually searched
      through a PDB id or some sequence information. However, in the HDAPD database
      presented here the protein structure of a disease-associated protein can be
      directly searched through the associated disease name keyed in. DESCRIPTION: The
      search in HDAPD can be easily initiated by keying some key words of a disease,
      protein name, protein type, or PDB id. The protein sequence can be presented in
      FASTA format and directly copied for a BLAST search. HDAPD is also interfaced
      with Jmol so that users can observe and operate a protein structure with Jmol.
      The gene ontological data such as cellular components, molecular functions, and
      biological processes are provided once a hyperlink to Gene Ontology (GO) is
      clicked. Further, HDAPD provides a link to the KEGG map such that where the
      protein is placed and its relationship with other proteins in a metabolic pathway
      can be found from the map. The latest literatures namely titles, journals,
      authors, and abstracts searched from PubMed for the protein are also presented as
      a length controllable list. CONCLUSIONS: Since the HDAPD data content can be
      routinely updated through a PHP-MySQL web page built, the new database presented
      is useful for searching the structures for some disease-associated proteins that
      may play important roles in the disease developing process for performing the
      structure-based drug design to against the diseases.

PMID- 20158921
TI  - 'Genome order index' should not be used for defining compositional constraints in
      nucleotide sequences--a case study of the Z-curve.
AB  - BACKGROUND: The Z-curve is a three dimensional representation of DNA sequences
      proposed over a decade ago and has been extensively applied to sequence
      segmentation, horizontal gene transfer detection, and sequence analysis. Based on
      the Z-curve, a "genome order index," was proposed, which is defined as S = a2+
      c2+t2+g2, where a, c, t, and g are the nucleotide frequencies of A, C, T, and G,
      respectively. This index was found to be smaller than 1/3 for almost all tested
      genomes, which was taken as support for the existence of a constraint on genome
      composition. A geometric explanation for this constraint has been suggested. Each
      genome was represented by a point P whose distance from the four faces of a
      regular tetrahedron was given by the frequencies a, c, t, and g. They claimed
      that an inscribed sphere of radius r = 1/ square root 3 contains almost all
      points corresponding to various genomes, implying that S <r2. The distribution of
      the points P obtained by S was studied using the Z-curve. RESULTS: In this work,
      we studied the basic properties of the Z-curve using the "genome order index" as
      a case study. We show that (1) the calculation of the radius of the inscribed
      sphere of a regular tetrahedron is incorrect, (2) the S index is narrowly
      distributed, (3) based on the second parity rule, the S index can be derived
      directly from the Shannon entropy and is, therefore, redundant, and (4) the Z
      curve suffers from over dimensionality, and the dimension stands for GC content
      alone suffices to represent any given genome. CONCLUSION: The "genome order
      index" S does not represent a constraint on nucleotide composition. Moreover, S
      can be easily computed from the Gini-Simpson index and be directly derived from
      entropy and is redundant. Overall, the Z-curve and S are over-complicated
      measures to GC content and Shannon H index, respectively.

PMID- 20158920
TI  - Promotion of the mind through exercise (PROMoTE): a proof-of-concept randomized
      controlled trial of aerobic exercise training in older adults with vascular
      cognitive impairment.
AB  - BACKGROUND: Sub-cortical vascular ischaemia is the second most common etiology
      contributing to cognitive impairment in older adults, and is frequently under
      diagnosed and under-treated. Although evidence is mounting that exercise has
      benefits for cognitive function among seniors, very few randomized controlled
      trials of exercise have been conducted in populations at high-risk for
      progression to dementia. Aerobic-based exercise training may be of specific
      benefit in delaying the progression of cognitive decline among seniors with
      vascular cognitive impairment by reducing key vascular risk factors associated
      with metabolic syndrome. Thus, we aim to carry out a proof-of-concept single
      blinded randomized controlled trial primarily designed to provide preliminary
      evidence of efficacy aerobic-based exercise training program on cognitive and
      everyday function among older adults with mild sub-cortical ischaemic vascular
      cognitive impairment. METHODS/DESIGN: A proof-of-concept single-blinded
      randomized trial comparing a six-month, thrice-weekly, aerobic-based exercise
      training group with usual care on cognitive and everyday function. Seventy older
      adults who meet the diagnostic criteria for sub-cortical ischaemic vascular
      cognitive impairment as outlined by Erkinjuntti and colleagues will be recruited
      from a memory clinic of a metropolitan hospital. The aerobic-based exercise
      training will last for 6 months. Participants will be followed for an additional
      six months after the cessation of exercise training. DISCUSSION: This research
      will be an important first step in quantifying the effect of an exercise
      intervention on cognitive and daily function among seniors with sub-cortical
      ischaemic vascular cognitive impairment, a recognized risk state for progression
      to dementia. Exercise has the potential to be an effective, inexpensive, and
      accessible intervention strategy with minimal adverse effects. Reducing the rate
      of cognitive decline among seniors with sub-cortical ischaemic vascular cognitive
      impairment could preserve independent functioning and health related quality of
      life in this population. This, in turn, could lead to reduced health care
      resource utilization costs and avoidance of early institutional care.

PMID- 20158922
TI  - Completeness of hepatitis, brucellosis, syphilis, measles and HIV/AIDS
      surveillance in Izmir, Turkey.
AB  - BACKGROUND: According to the surveillance system in Turkey, most diseases are
      notified only by clinicians, without involving laboratory notification. It is
      assumed that a considerable inadequacy in notifications exists; however, this has
      not been quantified by any researcher. Our aim was to evaluate the completeness
      of communicable disease surveillance in the province of Izmir, Turkey for the
      year of 2003 by means of estimating the incidences of diseases. METHODS: Data on
      positive laboratory results for the notifiable and serologically detectable
      diseases hepatitis A, B, C, brucellosis, syphilis, measles and HIV detected in
      2003 in Izmir (population 3.5 million) were collected from serology laboratories
      according to WHO surveillance standards and compared to the notifications
      received by the Provincial Health Directorate. Data were checked for duplicates
      and matched. Incidences were estimated with the capture-recapture method.
      Sensitivities of both notifications and laboratory data were calculated according
      to these estimates. RESULTS: Among laboratories performing serologic tests (n =
      158) in Izmir, 84.2% accepted to participate, from which 23,515 positive results
      were collected. Following the elimination of duplicate results as well as of
      cases residing outside of Izmir, the total number was 11,402. The total number of
      notifications was 1802. Notification rates of cases found in laboratories were
      31.6% for hepatitis A, 12.1% for acute hepatitis B, 31.8% for brucellosis, 25.9%
      for syphilis and 100% for HIV confirmation. CONCLUSIONS: It was discovered that
      for hepatitis A, B, C, brucellosis and syphilis, there is a considerable under
      notification by clinicians and that laboratory data has the potential of
      contributing greatly to their surveillance. The inclusion of laboratories in the
      surveillance system of these diseases could help to achieve completeness of
      reporting.

PMID- 20158923
TI  - An assessment of soybeans and other vegetable proteins as source of Salmonella
      contamination in pig production.
AB  - BACKGROUND: The impact of salmonella contaminated feed ingredients on the risk
      for spreading salmonella to pigs was assessed in response to two incidences when
      salmonella was spread by feed from two feed mills to 78 swine producing herds.
      METHODS: The assessment was based on results from the salmonella surveillance of
      feed ingredients before introduction to feed mills and from HACCP--based
      surveillance of the feed mills. Results from the mills of the Company (A) that
      produced the salmonella contaminated feed, were by the Chi. Square test compared
      to the results from all the other (B - E) feed producers registered in Sweden.
      Isolated serovars were compared to serovars from human cases of salmonellosis.
      RESULTS: Salmonella (28 serovars) was frequently isolated from imported
      consignments of soybean meal (14.6%) and rape seed meal (10.0%). Company A
      largely imported soybean meal from crushing plants with a history of unknown or
      frequent salmonella contamination. The risk for consignments of vegetable
      proteins to be salmonella contaminated was 2.4 times (P < 0.0006) larger for A
      when compared to the mills of the other companies which largely were supplied by
      soybean meal from a crushing plant with a low risk for salmonella contamination.
      Also the level of feed mill contamination of salmonella was higher for feed mills
      belonging to Company A in comparison to the other companies before and also after
      heat treatment. Four (10.5%) of the 38 serovars isolated from feed ingredients
      (28) and feed mills (10) were on the EU 2007 top ten list of human cases of
      salmonellosis and all but eight (78.9%) on a 12 year list (1997-2008) of cases of
      human salmonellosis in Sweden. CONCLUSIONS: Salmonella contaminated feed
      ingredients are an important source for introducing salmonella into the feed and
      food chain. Effective HACCP-based control and associated corrective actions are
      required to prevent salmonella contamination of feed. Efforts should be taken to
      prevent salmonella contamination already at the crushing plants. This is
      challenge for the EU - feed industry due to the fact that 98% of the use of
      soybean/meal, an essential feed ingredient, is imported from crushing plants of
      third countries usually with an unknown salmonella status.

PMID- 20158924
TI  - Detection of distant evolutionary relationships between protein families using
      theory of sequence profile-profile comparison.
AB  - BACKGROUND: Detection of common evolutionary origin (homology) is a primary means
      of inferring protein structure and function. At present, comparison of protein
      families represented as sequence profiles is arguably the most effective homology
      detection strategy. However, finding the best way to represent evolutionary
      information of a protein sequence family in the profile, to compare profiles and
      to estimate the biological significance of such comparisons, remains an active
      area of research. RESULTS: Here, we present a new homology detection method based
      on sequence profile-profile comparison. The method has a number of new features
      including position-dependent gap penalties and a global score system. Position
      dependent gap penalties provide a more biologically relevant way to represent and
      align protein families as sequence profiles. The global score system enables an
      analytical solution of the statistical parameters needed to estimate the
      statistical significance of profile-profile similarities. The new method,
      together with other state-of-the-art profile-based methods (HHsearch, COMPASS and
      PSI-BLAST), is benchmarked in all-against-all comparison of a challenging set of
      SCOP domains that share at most 20% sequence identity. For benchmarking, we use a
      reference ("gold standard") free model-based evaluation framework. Evaluation
      results show that at the level of protein domains our method compares favorably
      to all other tested methods. We also provide examples of the new method
      outperforming structure-based similarity detection and alignment. The
      implementation of the new method both as a standalone software package and as a
      web server is available at http://www.ibt.lt/bioinformatics/coma. CONCLUSION: Due
      to a number of developments, the new profile-profile comparison method shows an
      improved ability to match distantly related protein domains. Therefore, the
      method should be useful for annotation and homology modeling of uncharacterized
      proteins.

PMID- 20158925
TI  - Molecular differentiation of four Reptalus species (Hemiptera: Cixiidae).
AB  - The cixiid species Reptalus quinquecostatus, R. cuspidatus, R. panzeri and R.
      melanochaetus are widely distributed in Europe and are receiving growing
      attention because of their potential role as phytoplasma vectors. Identifying the
      Reptalus species is restricted to a few specialist entomologists and relies on
      the morphology of the male genitalia, hampering the identification of juveniles
      and females. This study provides the tools for species discrimination by
      integrating the morphological description, which is primarily for the genus
      identification, with new molecular assays, based on both ribosomal and
      mitochondrial DNA. PCR-RFLP assays carried out on the mitochondrial cytochrome
      oxidase I gene (COI) with AluI provided species-specific profiles for the four
      Reptalus species. Amplification of a ribosomal internal transcribed spacer (ITS2)
      region produced species-specific fragments of different sizes for R.
      quinquecostatus, R. melanochaetus, R. cuspidatus and R. panzeri. The digestion of
      the ITS2 PCR product with TaqI allowed the discrimination of these latter two
      species. This molecular identification key ensures reliable results and can be
      successfully applied not only to adults, but also to the nymphs feeding on the
      roots. The identification of the nymphs (i) extends the collection period of
      these monovoltine species to the whole year (adults are present for a short
      summer period) and (ii) allows the unambiguous identification of their actual
      host plants because nymphs are steady on the root system while adults tend to
      disperse onto other plants. Fast and reliable identification of the Reptalus
      species provides useful help in monitoring activities and, therefore, in
      designing rational control strategies to protect crops from phytoplasma
      infection.

PMID- 20158926
TI  - On the specific identity of specimens of Phytoseiulus longipes Evans
      (Mesostigmata: Phytoseiidae) showing different feeding behaviours: morphological
      and molecular analyses.
AB  - This paper focuses on the differentiation of specimens, identified as
      Phytoseiulus longipes, collected in four countries: Argentina, Brazil, Chile and
      South Africa. Two of these populations are known to feed and develop on
      Tetranychus evansi, whereas the two others do not. As morphologically similar
      specimens can sometimes belong to different species and because differences in
      predatory behaviours exist among the four populations considered, we tested for
      the presence of cryptic species. Morphological and molecular experiments (12S
      rDNA) were carried out. The four studied populations of P. longipes could be
      morphologically differentiated thanks to a combination of characters. However,
      these morphological differences are very small. The two populations that feed and
      develop on T. evansi (from Argentina and Brazil) are morphologically closer to
      each other than to the two other populations. Genetic distances among the four
      populations of P. longipes were very low, suggesting that despite their different
      feeding habits, all specimens belong to the same species. However, the
      populations associated with T. evansi showed some genetic differentiation from
      those that do not use this pest. This is the first time that this type of
      differentiation has been reported for the family Phytoseiidae. These results are
      of primary importance to ensure the success of biological control programs and to
      develop strains adapted to both crops and prey species.

PMID- 20158927
TI  - Predation by beetles (Carabidae, Staphylinidae) on eggs and juveniles of the
      Iberian slug Arion lusitanicus in the laboratory.
AB  - Arion lusitanicus has become a major pest species in western Norway in the last
      few years. This species originates from southern Europe but has been spread by
      humans over large parts of central and northern Europe during recent decades.
      Slugs have traditionally been controlled by the use of molluscicides; but, as
      these may have serious ecological side effects, biological control of slugs is
      highly desirable. Potential biological control agents include nematodes,
      gastropods and arthropods. In laboratory experiments, we tested whether five
      common predator beetles would feed on eggs and juveniles of A. lusitanicus. The
      species Carabus nemoralis, Nebria brevicollis, Pterostichus melanarius and
      Pterostichus niger (Carabidae) as well as Staphylinus erythropterus
      (Staphylinidae) were tested, of which only P. melanarius has been tested on A.
      lusitanicus previously. Nebria brevicollis did not feed on slug eggs or newly
      hatched slugs, but the remaining four species all killed and ate a large
      proportion of the eggs and hatchlings offered. Both P. melanarius and P. niger
      also destroyed A. lusitanicus eggs and hatchlings under conditions emulating
      those in the field. Prey size choice experiments were conducted by feeding C.
      nemoralis, P. niger and S. erythropterus on different sizes of A. lusitanicus.
      Carabus nemoralis was also given a choice between two slug species, A.
      lusitanicus and Deroceras reticulatum. A significant preference for slugs smaller
      than one gram was evident for C. nemoralis, while the other beetles struggled
      much more to overcome the mucus of juvenile slugs. No significant preference was
      found between A. lusitanicus and D. reticulatum as prey for C. nemoralis. We also
      discuss the feasibility of biological control of A. lusitanicus using beetle
      predators.

PMID- 20158928
TI  - Evidence for pre-zygotic reproductive barrier between the B and Q biotypes of
      Bemisia tabaci (Hemiptera: Aleyrodidae).
AB  - The degree of reproductive isolation between the B and Q biotypes of the whitefly
      Bemisia tabaci (Hemiptera: Aleyrodidae) is currently not clear. Laboratory
      experiments have shown that the two biotypes are capable of producing viable F1
      hybrids but that these females are sterile as their F2 generation failed to
      develop, indicating, most likely, a post-zygotic reproductive barrier. Here, we
      confirm, by molecular and ecological tools, that the B and Q biotypes of Israel
      are genetically isolated and provide two independent lines of evidence that
      support the existence of a pre-zygotic reproductive barrier between them.
      Firstly, monitoring of mating behaviors in homogeneous and heterogeneous couples
      indicated no copulation events in heterogeneous couples compared to approximately
      50% in homogeneous B and Q couples. Secondly, we could not detect the presence of
      sperm in the spermathecae of females from heterogeneous couples, compared to 50%
      detection in intra-B biotype crosses and 15% detection in intra-Q biotype
      crosses. The existence of pre-zygotic reproductive barriers in Israeli B and Q
      colonies may indicate a reinforcement process in which mating discrimination is
      strengthened between sympatric taxa that were formerly allopatric, to avoid
      maladaptive hybridization. As the two biotypes continued to perform all courtship
      stages prior to copulation, we also conducted mixed cultures experiments in order
      to test the reproductive consequences of inter-biotype courtship attempts. In
      mixed cultures, a significant reduction in female fecundity was observed for the
      Q biotype but not for the B biotype, suggesting an asymmetric reproductive
      interference effect in favour of the B biotype. The long-term outcome of this
      effect is yet to be determined since additional environmental forces may reduce
      the probability of demographic displacement of one biotype by the other in
      overlapping niches.

PMID- 20158929
TI  - Key factors affecting the spring emergence of pea moth (Cydia nigricana).
AB  - The hypothesis that spring emergence of the pea moth Cydia nigricana is regulated
      by environmental factors, particularly photoperiod and temperature, was examined
      in this study. A long-term field study was conducted in two distinct pea-growing
      areas in Hesse and Saxony, Germany. Strong correlations between the flight
      phenology of pea moth in spring and air temperature, soil temperature, solar
      radiation and day length were demonstrated for three consecutive years. In
      laboratory experiments, we elucidated the interaction of different photoperiod
      temperature regimes, verifying cumulative day-degree data in relation to pea moth
      emergence rates in the field. C. nigricana temperature sensitivity is apparently
      initiated by long day conditions with a critical day length of about 14 h L:D.
      The overall results contribute to the theory that photoperiod and temperature
      interact as regulatory cues for spring emergence of C. nigricana. The findings
      are discussed in terms of the development of predictive models and decision
      support systems for pea moth control.

PMID- 20158930
TI  - A Middle East subregional laboratory-based surveillance network on foodborne
      diseases established by Jordan, Israel, and the Palestinian Authority.
AB  - In late 2002, health professionals from the ministries of health and academia of
      Jordan, the Palestinian Authority and Israel formed the Middle East Consortium on
      Infectious Disease Surveillance (MECIDS) to facilitate trans-border cooperation
      in response to infectious disease outbreaks. The first mission of MECIDS was to
      establish a regional, laboratory-based surveillance network on foodborne
      diseases. The development of harmonized methodologies and laboratory capacities,
      the establishment of a common platform of communication, data sharing and
      analysis and coordination of intervention steps when needed were agreed upon.
      Each of the three parties selected the microbiological laboratories that would
      form the network of sentinel laboratories and cover the different districts of
      each country and also designated one laboratory as the National Reference
      Laboratory (NRL). Data analysis units have been established to manage the data
      and serve as a central point of contact in each country. The MECIDS also selected
      a regional data analysis unit, the Cooperative Monitoring Centre (CMC) located in
      Amman, Jordan, and established a mechanism for sharing data from the national
      systems. Joint training courses were held on interventional epidemiology and
      laboratory technologies. Data collection started in July 2005 with surveillance
      of salmonellosis as the first target. This network of collaboration and
      communication established in an area of continuous dispute represents an
      important step towards assessing the burden of foodborne diseases in the region
      and is expected to be fundamental for coordination of public health interventions
      and prevention strategies.

PMID- 20158931
TI  - Pregnancy-associated listeriosis.
AB  - Infection by Listeria monocytogenes in pregnant women may result in fetal loss or
      invasive disease in the newborn. We examined listeriosis cases reported through
      the U.S. Listeria Initiative during 2004-2007. Cases were classified as pregnancy
      associated if illness occurred in a pregnant woman or an infant aged <28 days. Of
      758 reported Listeria cases, 128 (16.9%) were pregnancy-associated. Maternal
      infection resulted in four neonatal deaths and 26 (20.3%) fetal losses. Invasive
      illnesses in newborns (n=85) were meningitis (32.9%) and sepsis (36.5%). Pregnant
      women with Listeria were more likely to report Hispanic ethnicity (52.8% vs.
      25.6%, respectively; OR 3.3 95% CI 2.2-4.8) than mothers giving live birth in the
      USA during 2005 and were more likely to report consumption of Mexican-style
      cheese (OR 2.6, 95% CI 1.6-4.2) than were non-pregnant patients with Listeria
      infection. Pregnant woman comprised a considerable proportion of reported
      listeriosis cases. Further declines in pregnancy-associated listeriosis will
      require education about avoiding high-risk foods, and continued regulatory and
      industry efforts to decrease Listeria in foods.

PMID- 20158932
TI  - Modelling seasonality and viral mutation to predict the course of an influenza
      pandemic.
AB  - As the 2009 H1N1 influenza pandemic (H1N1) has shown, public health decision
      makers may have to predict the subsequent course and severity of a pandemic. We
      developed an agent-based simulation model and used data from the state of Georgia
      to explore the influence of viral mutation and seasonal effects on the course of
      an influenza pandemic. We showed that when a pandemic begins in April certain
      conditions can lead to a second wave in autumn (e.g. the degree of seasonality
      exceeding 0.30, or the daily rate of immunity loss exceeding 1% per day).
      Moreover, certain combinations of seasonality and mutation variables reproduced
      three-wave epidemic curves. Our results may offer insights to public health
      officials on how to predict the subsequent course of an epidemic or pandemic
      based on early and emerging viral and epidemic characteristics and what data may
      be important to gather.

PMID- 20158933
TI  - Dopamine release induced by atypical antipsychotics in prefrontal cortex requires
      5-HT(1A) receptors but not 5-HT(2A) receptors.
AB  - Atypical antipsychotic drugs (APDs) increase dopamine (DA) release in prefrontal
      cortex (PFC), an effect probably mediated by the direct or indirect activation of
      the 5-HT(1A) receptor (5-HT(1A)R). Given the very low in-vitro affinity of most
      APDs for 5-HT(1A)Rs and the large co-expression of 5-HT(1A)Rs and 5-HT(2A)
      receptors (5-HT(2A)Rs) in the PFC, this effect might result from the imbalance of
      5-HT(1A)R and 5-HT(2A)R activation after blockade of these receptors by APDs, for
      which they show high affinity. Here we tested this hypothesis by examining the
      dependence of the APD-induced DA release in medial PFC (mPFC) on each receptor by
      using in-vivo microdialysis in wild-type (WT) and 5-HT(1A)R and 5-HT(2A)R
      knockout (KO) mice. Local APDs (clozapine, olanzapine, risperidone) administered
      by reverse dialysis induced a dose-dependent increase in mPFC DA output equally
      in WT and 5-HT(2A)R KO mice whereas the DA increase was absent in 5-HT(1A)R KO
      mice. To examine the relative contribution of both receptors to the clozapine
      induced DA release in rat mPFC, we silenced G-protein-coupled receptors (GPCRs)
      in vivo with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) while 5
      HT(1A)Rs or 5-HT(2A)/2CRs in the mPFC were selectively protected with the
      respective antagonists WAY-100635 or ritanserin. The inactivation of GPCRs while
      preserving ~70% of 5-HT(2A)/(2C)Rs prevented the clozapine-induced DA rise in
      mPFC. In contrast, clozapine increased DA in mPFC of EEDQ-treated rats whose 5
      HT(1A)Rs were protected (~50% of control rats). These results indicate that (1) 5
      HT(1A)Rs are necessary for the APDs-induced elevation in cortical DA
      transmission, and (2) this effect does not require 5-HT(2A)R blockade by APDs.

PMID- 20158935
TI  - Letter to the Editor: An agenda for the next decade of psychotherapy research and
      practice.

PMID- 20158934
TI  - Sex differences in the activity of signalling pathways and expression of G
      protein-coupled receptor kinases in the neonatal ventral hippocampal lesion model
      of schizophrenia.
AB  - Animals with the neonatal ventral hippocampal lesion (NVHL) demonstrate altered
      responsiveness to stress and various drugs reminiscent of that in schizophrenia.
      Post-pubertal onset of abnormalities suggests the possibility of sex differences
      in NVHL effects that may model sex differences in schizophrenia. Here we
      demonstrate that novelty- and MK-801-induced hyperactivity is evident in both
      male and female NVHL rats, whereas only NVHL males were hyperactive in response
      to apomorphine. Next, we examined the sex- and NVHL-dependent differences in the
      activity of the ERK and Akt pathways. The basal activity of both pathways was
      higher in females than in males. NVHL reduces the level of phosphorylation of
      ERK1/2, Akt, and GSK-3 in both sexes, although males show more consistent down
      regulation. Females had higher levels of G-protein-coupled kinases [G-protein
      coupled receptor kinase (GRK)] 3 and 5, whereas the concentrations of other GRKs
      and arrestins were the same. In the nucleus accumbens, the concentration of GRK5
      in females was elevated by NVHL to the male level. The data demonstrate profound
      sex differences in the expression and activity of signalling molecules that may
      underlie differential susceptibility to schizophrenia.

PMID- 20158936
TI  - Central carbon metabolism of Leishmania parasites.
AB  - Leishmania spp. are sandfly-transmitted protozoa parasites that cause a spectrum
      of diseases in humans. Many enzymes involved in Leishmania central carbon
      metabolism differ from their equivalents in the mammalian host and are potential
      drug targets. In this review we summarize recent advances in our understanding of
      Leishmania central carbon metabolism, focusing on pathways of carbon utilization
      that are required for growth and pathogenesis in the mammalian host. While
      Leishmania central carbon metabolism shares many features in common with other
      pathogenic trypanosomatids, significant differences are also apparent. Leishmania
      parasites are also unusual in constitutively expressing most core metabolic
      pathways throughout their life cycle, a feature that may allow these parasites to
      exploit a range of different carbon sources (primarily sugars and amino acids)
      rapidly in both the insect vector and vertebrate host. Indeed, recent gene
      deletion studies suggest that mammal-infective stages are dependent on multiple
      carbon sources in vivo. The application of metabolomic approaches, outlined here,
      are likely to be important in defining aspects of central carbon metabolism that
      are essential at different stages of mammalian host infection.

PMID- 20158937
TI  - Metabolomic systems biology of trypanosomes.
AB  - Metabolomics analysis, which aims at the systematic identification and
      quantification of all metabolites in biological systems, is emerging as a
      powerful new tool to identify biomarkers of disease, report on cellular responses
      to environmental perturbation, and to identify the targets of drugs. Here we
      discuss recent developments in metabolomic analysis, from the perspective of
      trypanosome research, highlighting remaining challenges and the most promising
      areas for future research.

PMID- 20158938
TI  - Prevention of obesity in preschool children.
AB  - Obesity is a serious problem that affects children from diverse ethnic
      backgrounds in both industrialised and developing countries. Worldwide, an
      estimated twenty-two million children <5 years of age were overweight in 2007. In
      the UK if current trends continue an estimated one-quarter of all children <16
      years of age will be obese by 2050. Recent evidence suggests that most obesity is
      established during the preschool years, and because one in five obese 4 year olds
      will become obese adults this situation has major implications for public health.
      The causes of obesity in preschool children are complex and multifactorial.
      Although 30-50% of the predisposition towards obesity in preschool children can
      be explained by genetic factors, environmental influences also play a crucial
      role. The preschool period in particular is a pivotal time during which long-term
      dietary and physical activity habits are established, with potential lifelong
      effects on health. However, research in this age-group is limited. Previous
      studies have aimed to improve diet, increase physical activity and achieve
      behavioural change. However, few of these studies have been successful and there
      is an urgent need, therefore, for the development of evidence-based interventions
      aimed at the prevention of preschool obesity.

PMID- 20158939
TI  - Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the
      metabolic syndrome.
AB  - Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in
      both adults and children worldwide. As a disease spectrum, NAFLD may progress
      from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An
      estimated 20-35% of the general population has steatosis, 10% of whom will
      develop the more progressive non-alcoholic steatohepatitis associated with
      markedly increased risk of cardiovascular- and liver-related mortality.
      Development of NAFLD is strongly linked to components of the metabolic syndrome
      including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The
      recognition that NAFLD is an independent risk factor for CVD is a major public
      health concern. There is a great need for a sensitive non-invasive test for the
      early detection and assessment of the stage of NAFLD that could also be used to
      monitor response to treatment. The cellular and molecular aetiology of NAFLD is
      multi-factorial; genetic polymorphisms influencing NAFLD have been identified and
      nutrition is a modifiable environmental factor influencing NAFLD progression.
      Weight loss through diet and exercise is the primary recommendation in the
      clinical management of NAFLD. The application of systems biology to the
      identification of NAFLD biomarkers and factors involved in NAFLD progression is
      an area of promising research.

PMID- 20158940
TI  - The role of inflammation and macrophage accumulation in the development of
      obesity-induced type 2 diabetes mellitus and the possible therapeutic effects of
      long-chain n-3 PUFA.
AB  - The WHO estimate that >1 x 10(6) deaths in Europe annually can be attributed to
      diseases related to excess body weight, and with the rising global obesity levels
      this death rate is set to drastically increase. Obesity plays a central role in
      the metabolic syndrome, a state of insulin resistance that predisposes patients
      to the development of CVD and type 2 diabetes mellitus. Obesity is associated
      with low-grade chronic inflammation characterised by inflamed adipose tissue with
      increased macrophage infiltration. This inflammation is now widely believed to be
      the key link between obesity and development of insulin resistance. In recent
      years it has been established that activation of pro-inflammatory pathways can
      cross talk with insulin signalling pathways via a number of mechanisms including
      (a) down-regulation of insulin signalling pathway proteins (e.g. GLUT4 and
      insulin receptor substrate (IRS)-1), (b) serine phosphorylation of IRS-1 blocking
      its tyrosine phosphorylation in response to insulin and (c) induction of cytokine
      signalling molecules that sterically hinder insulin signalling by blocking
      coupling of the insulin receptor to IRS-1. Long-chain (LC) n-3 PUFA regulate gene
      expression (a) through transcription factors such as PPAR and NF-kappaB and (b)
      via eicosanoid production, reducing pro-inflammatory cytokine production from
      many different cells including the macrophage. LC n-3 PUFA may therefore offer a
      useful anti-inflammatory strategy to decrease obesity-induced insulin resistance,
      which will be examined in the present review.

PMID- 20158941
TI  - Beyond antioxidants: the cellular and molecular interactions of flavonoids and
      how these underpin their actions on the brain.
AB  - The consumption of flavonoid-rich foods and beverages has been suggested to limit
      the neurodegeneration associated with a variety of neurological disorders and to
      prevent or reverse normal or abnormal deteriorations in cognitive performance.
      Flavonoids mediate these effects via a number of routes, including a potential to
      protect neurons against injury induced by neurotoxins, an ability to suppress
      neuroinflammation and a potential to promote memory, learning and cognitive
      function. Originally, it was thought that such actions were mediated by the
      antioxidant capacity of flavonoids. However, their limited absorption and their
      low bioavailability in the brain suggest that this explanation is unlikely.
      Instead, this multiplicity of effects appears to be underpinned by three separate
      processes: first, through their interactions with important neuronal and glial
      signalling cascades in the brain, most notably the phosphatidylinositol 3
      kinase/Akt and mitogen-activated protein kinase pathways that regulate pro
      survival transcription factors and gene expression; second, through an ability to
      improve peripheral and cerebral blood flow and to trigger angiogenesis and
      neurogenesis in the hippocampus; third, by their capacity to directly react with
      and scavenge neurotoxic species and pro-inflammatory agents produced in the brain
      as a result of both normal and abnormal brain ageing. The present review explores
      the potential inhibitory or stimulatory actions of flavonoids within these three
      systems and describes how such interactions are likely to underlie neurological
      effects.

PMID- 20158943
TI  - 7,12-dimethylbenz[a]anthracene induces sertoli-leydig-cell tumors in the follicle
      depleted ovaries of mice treated with 4-vinylcyclohexene diepoxide.
AB  - Ovarian cancer is associated with high mortality due to its late onset of
      symptoms and lack of reliable screening methods for early detection. Furthermore,
      the incidence of ovarian cancer is higher in postmenopausal women. Mice rendered
      follicle-depleted through treatment with 4-vinylcyclohexene diepoxide (VCD) are a
      model of ovary-intact menopause. The present study was designed to induce ovarian
      neoplasia in this model by treating mice with 7,12-dimethylbenz[a]anthracene
      (DMBA). Female B6C3F1 mice (age, 28 d) received intraperitoneal sesame oil
      (vehicle; VCD- groups) as a control or VCD (160 mg/kg; VCD+ groups) daily for 20
      d to cause ovarian failure. Four months after the onset of dosing, mice from each
      group received a single injection of DMBA (VCD-DMBA+ and VCD+DMBA+ groups, n = 15
      per group) or vehicle control (VCD-DMBA-, n = 15; VCD+ DMBA-, n = 14) under the
      bursa of the right ovary. Ovaries were collected 3 or 5 mo after injection and
      processed for histologic evaluation. Immunohistochemistry was used to confirm
      classification of neoplasms. None of the animals in the VCD-DMBA- and VCD-DMBA+
      groups (that is, mice still undergoing estrus) had tumors at either time point.
      At the 3-mo time point, 12.5% of the VCD+DMBA+ mice had ovarian tumors; at 5 mo,
      57.1% of the VCD+DMBA+ and 14.3% of VCD+DMBA- ovaries had neoplasms. Neoplasms
      stained positively for inhibin alpha (granulosa cells) and negatively for keratin
      7 (surface epithelium), thus confirming classification of the lesions as Sertoli
      Leydig cell tumors. These findings provide evidence for an increased incidence of
      DMBA-induced ovarian neoplasms in the ovaries of follicle-depleted mice compared
      with that in age-matched cycling controls.

PMID- 20158944
TI  - Perturbations in cytokine gene expression after inoculation of C57BL/6 mice with
      Pasteurella pneumotropica.
AB  - Pasteurella pneumotropica can cause inflammation and abscess formation in a
      variety of tissues. Most commonly, P. pneumotropica produces clinical disease in
      immunodeficient mice or those concurrently infected with other pathogens. Because
      clinical disease is infrequent in immunocompetent mice harboring P.
      pneumotropica, some scientists consider it an opportunistic pathogen with little
      clinical relevance to biomedical research. However, other infectious agents,
      including mouse parvoviruses, mouse rotavirus, and Helicobacter spp. alter
      physiologic or biologic responses without causing clinical signs of illness. We
      investigated the potential for P. pneumotropica to modulate the transcription of
      cytokine genes in immunocompetent mice. In C57BL/6 mice inoculated oronasally
      with a minimal colonizing dose of P. pneumotropica, modest but statistically
      significant elevations of IL1beta, TNFalpha, CCL3, CXCL1, and CXCL2 mRNA were
      detected in mandibular and superficial cervical lymph nodes at 7 d after
      inoculation, and upregulation of IL1beta mRNA was detected 28 d after
      inoculation. These perturbations were not present in C57/BL6 mice inoculated with
      heat killed-P. pneumotropica or the related bacterium Actinobacillus muris. Nasal
      mucosal cytokine transcription did not vary significantly in C57BL/6 mice given a
      high dose of P. pneumotropica. These data indicate that slight and transient
      experimental perturbations are possible in immunocompetent mice colonized with P.
      pneumotropica. Knowing the full health status of experimental mice is paramount
      to avoid unwanted experimental variables, especially when using exquisitely
      sensitive testing methodologies such as those for quantification of gene
      expression.

PMID- 20158945
TI  - Spontaneous coagulopathy in inbred WAG/RijYcb rats.
AB  - Here we describe a series of cases of spontaneous coagulopathy in a colony of
      inbred WAG/RijYcb (WAG/RijY) rats. This strain previously had been bred at our
      institution without symptomatology for several decades. The index case was a 10
      wk-old male rat that developed a large hematoma at a subcutaneous injection site.
      Clinicopathologic findings included a decreased RBC count, decreased hematocrit,
      decreased hemoglobin concentration, normal PT, and prolonged (50% to 70%) aPTT
      (52 s; reference, 15 to 33 s). Examination of additional WAG/RijY rats that died
      unexpectedly or had clinical signs of bleeding in the absence of experimental
      manipulation also revealed normal PT and prolonged aPTT. Histologic examinations
      of tissues from all rats were unremarkable except for severe acute focally
      extensive hemorrhage corresponding to the macroscopic findings of acute
      hemorrhage. Furthermore the aPTT in 8 clinically normal adult rats and 8
      clinically normal 4-wk-old WAG/RijY littermates of both sexes was prolonged. We
      conclude that these WAG/RijY rats have an inherited defect in the intrinsic
      coagulation pathway.

PMID- 20158947
TI  - Refinement of pig retroperfusion technique: Global retroperfusion with ligation
      of the azygos connection preserves hemodynamic function in an acute infarction
      model in pigs (Sus scrofa domestica).
AB  - In ischemic hearts, venous retroperfusion is a potential myocardial
      revascularization strategy. This study aimed to refine the technical and
      functional aspects of a pig model of acute myocardial infarction and
      retroperfusion with respect to the azygos connection. Global retroperfusion after
      ligation of the ramus interventricularis paraconalis (equivalent to the left
      anterior descending artery in humans) was performed in 16 Landrace pigs (Sus
      scrofa domestica). Coronary sinus perfusion was performed in 8 pigs (P+) but not
      in the other 8 (P-), and the azygos vein was ligated (L+) 4 of the 8 pigs in each
      of these groups but left open (L-) in the remaining animals. Hemodynamic
      performance (for example, cardiac output, stroke volume) was significantly better
      in P+L+ pigs that underwent coronary sinus perfusion with ligation of the azygos
      vein compared with all other animals. In addition, troponin I release was
      significant lower in P+L+ pigs (1.7 +/- 1.3 ng/mL) than in P-L- (5.47 +/- 2.1
      ng/mL), P-L+ (6.63 +/- 2.4 ng/mL), and P+L- (4.81 +/- 2.3 ng/mL) pigs. Effective
      retrograde flow and thus hemodynamic stability was achieved by ligation of the
      azygos vein. Therefore, experiments focusing on global retroperfusion will
      benefit from effective inhibition of the blood flow through the azygos vein.

PMID- 20158946
TI  - Escherichia coli O157:H7 infection in Dutch belted and New Zealand white rabbits.
AB  - Enterohemorrhagic Escherichia coli (EHEC) produce one or more types of Shiga
      toxins and are foodborne causes of bloody diarrhea. The prototype EHEC strain,
      Escherichia coli O157:H7, is responsible for both sporadic cases and serious
      outbreaks worldwide. Infection with E. coli that produce Shiga toxins may lead to
      diarrhea, hemorrhagic colitis, or (less frequently) hemolytic uremic syndrome,
      which can cause acute kidney failure. The exact mechanism by which EHEC evokes
      intestinal and renal disease has not yet been determined. The development of a
      readily reproducible animal oral-infection model with which to evaluate the full
      pathogenic potential of E. coli O157:H7 and assess the efficacy of therapeutics
      and vaccines remains a research priority. Dutch belted (DB) rabbits are reported
      to be susceptible to both natural and experimental EHEC-induced disease, and New
      Zealand white (NZW) rabbits are a model for the intestinal manifestations of EHEC
      infection. In the current study, we compared the pathology caused by E. coli
      O157:H7 infection in DB and NZW rabbits. Both breeds of rabbits developed
      clinical signs of disease and intestinal lesions after experimental infection. In
      addition, one of the infected DB rabbits developed renal lesions. Our findings
      provide evidence that both breeds are susceptible to E. coli O157:H7 infection
      and that both may be useful models for investigating EHEC infections of humans.

PMID- 20158948
TI  - Infection of cesarean-derived colostrum-deprived pigs with porcine circovirus
      type 2 and Swine influenza virus.
AB  - Porcine circovirus type 2 (PCV2) and swine influenza virus (SIV) are important
      pathogens for porcine respiratory disease complex, which is economically
      significant worldwide. The pathogenesis of PCV2-SIV coinfection is unknown. In
      this study, we focused on establishing a challenge model for PCV2 to determine
      whether SIV influences PCV2 replication and increases the severity of PCV2
      associated disease. Cesarean-derived colostrum-deprived pigs were inoculated
      intratracheally with cell culture medium only (negative control group), PCV2
      only, or PCV2 followed 1 wk later with SIV H1N1. Two pigs from each group were
      necropsied at 12, 21, 28, and 35 d after inoculation. Coinfection with SIV did
      not increase the number of PCV2 genomic copies in serum or target tissues or the
      severity of microscopic lesions associated with PCV2 in lung or lymph node. The
      antibody titer to PCV2 did not differ significantly between PCV2-SIV- and PCV2
      infected groups. In conclusion, SIV H1N1 did not influence PCV2 replication in
      dually infected pigs in this study.

PMID- 20158949
TI  - Simian betaretrovirus infection in a colony of cynomolgus monkeys (Macaca
      fascicularis).
AB  - Of the 419 laboratory-bred cynomolgus macaques (Macaca fascicularis) in a
      breeding colony at our institution, 397 (95%) exhibited antibodies or viral RNA
      (or both) specific for simian betaretrovirus (SRV) in plasma. Pregnant monkeys
      (n= 95) and their offspring were tested to evaluate maternal-infant infection
      with SRV. At parturition, the first group of pregnant monkeys (n = 76) was
      antibody-positive but RNA-negative, the second group (n = 14 monkeys) was
      positive for both antibody and RNA, and the last group (n = 5) was antibody
      negative but RNA-positive. None of the offspring delivered from the 76 antibody
      positive/RNA-negative mothers exhibited viremia at birth. Eight of the offspring
      (including two newborns delivered by caesarian section) from the 14 dually
      positive mothers exhibited SRV viremia, whereas the remaining 6 newborns from
      this group were not viremic. All of the offspring (including 2 newborns delivered
      by caesarian section) of the 5 antibody-negative/RNA-positive mothers exhibited
      viremia at birth. One neonatal monkey delivered by CS and two naturally delivered
      monkeys that were viremic at birth remained viremic at 1 to 6 mo of age and
      lacked SRV antibodies at weaning. Family analysis of 2 viremic mothers revealed
      that all 7 of their offspring exhibited SRV viremia, 6 of which were also
      antibody-negative. The present study demonstrates the occurrence of
      transplacental infection of SRV in viremic dams and infection of SRV in utero to
      induce immune tolerance in infant monkeys.

PMID- 20158950
TI  - A challenge model for Shigella dysenteriae 1 in cynomolgus monkeys (Macaca
      fascicularis).
AB  - Shigella dysenteriae type 1 can cause devastating pandemics with high case
      fatality rates; a vaccine for Shigella is unavailable currently. Because of the
      risks associated with performing challenge studies with wild-type S. dysenteriae
      1 in human clinical trials to advance vaccine development, an improved nonhuman
      primate model is needed urgently. In the present study, cynomolgus macaques
      (Macaca fascicularis) were challenged with various doses of S. dysenteriae 1
      strain 1617 to establish a dose that would produce shigellosis. Further,
      different routes of delivery of S. dysenteriae 1 were compared to establish the
      most appropriate route for infection. Animals receiving 10(11) cfu S. dysenteriae
      1 intragastrically consistently developed signs of shigellosis characterized by
      the onset of diarrhea and dysentery within 2 to 3 d. Administration of as many as
      10(9) cfu S. dysenteriae 1 intraduodenally did not elicit signs characteristic of
      infection in macaques despite fecal shedding of bacteria for as long as 10 d. S.
      dysenteriae 1 administered intraduodenally at 10(9) cfu or intragastrically at
      10(11) cfu elicited robust IgG and IgA antibody responses to LPS. We have
      developed a reliable challenge model of infection with wild-type S. dysenteriae 1
      in cynomolgus macaques that reproducibly induces disease and elicits robust
      immune responses. We believe that this animal model may provide unique insights
      into the immunologic mechanisms of protection to S. dysenteriae 1 infection and
      in advancing development of a vaccine against shigellosis.

PMID- 20158951
TI  - Alterations in cytokines and effects of dexamethasone immunosuppression during
      subclinical infections of invasive Klebsiella pneumoniae with hypermucoviscosity
      phenotype in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis)
      macaques.
AB  - Invasive Klebsiella pneumoniae with the hypermucoviscosity phenotype (HMV K.
      pneumoniae) is an emerging human pathogen that also has been attributed to fatal
      multisystemic disease in African green monkeys at our institution. Combining a
      cluster of subclinically infected macaques identified in March and April 2008 and
      the animals documented during a subsequent survey of more than 300 colony
      nonhuman primates yielded a total of 9 rhesus macaques and 6 cynomolgus macaques
      that were subclinically infected. In an attempt to propagate the responsible HMV
      K. pneumoniae strain, a subset of these animals was immunosuppressed with
      dexamethasone. None of the treated animals developed clinical disease consistent
      with the multisystemic disease that affected colony African green monkeys.
      However, cytokine analysis revealed significant alterations of secreted cytokines
      in macaques subclinically infected with HMV K. pneumoniae when compared with
      noninfected macaques, thereby calling into question the suitability of animals
      subclinically infected with HMV K. pneumoniae for use in immunologic or
      infectious disease research.

PMID- 20158952
TI  - Orally ingested (13)C(2)-retinol is incorporated into hepatic retinyl esters in a
      nonhuman primate (Macaca mulatta) model of hypervitaminosis A.
AB  - The mechanism responsible for the metabolism of vitamin A during hypervitaminosis
      is largely unknown. This study investigated hepatic (13)C-retinol uptake in
      hypervitaminotic A rhesus monkeys. We hypothesized that individual retinyl esters
      would be enriched in (13)C after a physiologic dose of (13)C(2)-retinyl acetate,
      thus suggesting de novo in vivo hepatic retinol esterification. Male rhesus
      macaques (n = 16; 11.8 +/- 2.9 y) each received 3.5 micromol 14, 15-(13)C(2)
      retinyl acetate. Blood was drawn at baseline and 5 h and 2, 4, 7, 14, 21, and 28
      d after administration. Liver biopsies were collected 7 d before and 2 d after
      dose administration (n = 4) and at 7, 14, and 28 d after dose administration (n =
      4 per time point). (13)C enrichments of retinol and retinyl esters HPLC-purified
      from liver samples were measured by using gas chromatography-combustion-isotope
      ratio mass spectrometry. (13)C enrichment of total vitamin A and individual
      retinyl esters were significantly greater 2 d after dose administration compared
      with baseline levels. In contrast, the concentration of isolated retinyl esters
      did not always increase 2 d after treatment. Given that the liver biopsy site
      differed between monkeys, these data suggest that the accumulation of hepatic
      retinyl esters is a dynamic process that is better represented by combining
      analytical techniques. This sensitive methodology can be used to characterize
      vitamin A trafficking after physiologic doses of (13)C-retinol. In this nonhuman
      primate model of hypervitaminosis A, hepatic retinyl esters continued to
      accumulate with high liver stores.

PMID- 20158953
TI  - The temporal stability and predictive validity of pupils' causal attributions for
      difficult classroom behaviour.
AB  - BACKGROUND: Recent studies have investigated the causal attributions for
      difficult pupil behaviour made by teachers, pupils, and parents but none have
      investigated the temporal stability or predictive validity of these attributions.
      AIMS: This study examines the causal attributions made for difficult classroom
      behaviour by students on two occasions 30 months apart. The longitudinal
      stability of these attributions is considered as is the predictive validity of
      the first set of attributions in relation to teachers' later judgments about
      individual students' behaviour. SAMPLE: Two hundred and seventeen secondary
      school age pupils (114 males, 103 females) provided data on the two occasions.
      Teachers also rated each student's behaviour at the two times. METHOD: A
      questionnaire listing 63 possible causes of classroom misbehaviour was delivered
      to pupils firstly when they were in Year 7 (aged 11-12) and then again, 30 months
      later. Responses were analysed through exploratory factor analysis (EFA).
      Additionally, teachers were asked to rate the standard of behaviour of each of
      the students on the two occasions. RESULTS: EFA of the Years 7 and 10 data
      indicated that pupils' attributions yielded broadly similar five-factor models
      with the perceived relative importance of these factors remaining the same.
      Analysis also revealed a predictive relationship between pupils' attributions
      regarding the factor named culture of misbehaviour in Year 7, and teachers'
      judgments of their standard of behaviour in Year 10. CONCLUSION: The present
      study suggests that young adolescents' causal attributions for difficult
      classroom behaviour remain stable over time and are predictive of teachers' later
      judgments about their behaviour.

PMID- 20158954
TI  - Correlation of findings in advanced MR techniques with global severity scales in
      patients with some grade of cognitive impairment.
AB  - INTRODUCTION: Some previous studies in patients with mild cognitive impairment
      and Alzheimer's disease have probed changes in the results of (1)H magnetic
      resonance spectroscopy and perfusion- and diffusion-weighted imaging. The purpose
      of this work was to correlate the results of perfusion- and diffusion-weighted
      imaging and magnetic resonance spectroscopy with the results of two global
      severity scales in cognitive impairment: the clinical dementia rating (CDR) and
      the global deterioration scale (GDS). PATIENTS AND METHODS: We evaluated 87
      patients with cognitive impairment of diverse grade (35 men and 52 women; mean
      age, 70.2 +/- 8.5 years old). All patients were evaluated by a neurological team
      in our hospital. They applied both global severity scales (CDR and GDS) and
      referred the patients to our diagnostic imaging department to make a cerebral
      magnetic resonance imaging study and studies of diffusion- and perfusion-weighted
      imaging and magnetic resonance spectroscopy. We excluded patients with history of
      Parkinson's disease, frontotemporal dementia, cerebrovascular disease,
      intracranial tumors, hydrocephaly, epilepsy, alcoholism and psychiatric
      disorders. Magnetic resonance spectroscopy was carried out in the left occipital
      cortex and in the posterior cingulate gyrus. The evaluated metabolites were N
      acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI). After
      diffusion-weighted imaging, we calculated apparent diffusion coefficient values
      in the region of interest located in hippocampi, white matter of temporal lobes,
      occipital lobes, parietal lobes, frontal lobes and posterior cingulate gyrus of
      both hemispheres. In perfusion-weighted imaging, we calculated the relative
      cerebral blood volume in hippocampi, gray matter of frontal lobes, occipital
      lobes, temporoparietal regions, posterior cingulate gyri and somatic-sensorial
      cortex. We used Spearman coefficient to analyse the correlation among the
      different factors. Statistical analysis was made with SPSS 14 software. RESULTS:
      We found 33 patients with Alzheimer's disease and 54 with mild cognitive
      impairment. The Spearman coefficient had statistical significance in the
      correlation of CDR and GDS (R(2)=0.596, p<0.001). Magnetic resonance spectroscopy
      showed a good correlation between ratios of NAA/Cr and NAA/mI with CDR and GDS in
      both evaluated regions and a weak correlation between Cho/Cr in the left
      occipital lobe and GDS. In diffusion-weighted imaging, we found a weak
      correlation between GDS and apparent diffusion coefficient values in hippocampi,
      temporal lobes, left frontal lobe and left occipital lobe. Finally, perfusion
      showed a weak correlation between GDS and relative cerebral blood volume in
      occipital lobes and posterior cingulate gyrus. CONCLUSION: In patients with
      cognitive impairment, there is a good correlation between CDR and GDS. The tool
      that showed the closest correlation with the clinical scales (CDR and GDS) was
      magnetic resonance spectroscopy in the left occipital cortex and posterior
      cingulate gyrus. Perfusion- and diffusion-weighted imaging are tools with a weak
      correlation with clinical scales, GDS being unique that gave us significant
      statistical results; this could be explained by the major number of items
      considered for cognitive impairment (GDS 2 and 3) compared with CDR (CDR 0.5).
      Magnetic resonance spectroscopy can be used in the diagnostic, following and
      evaluation of the response to the treatment in patients with cognitive impairment
      (mild cognitive impairment and Alzheimer's disease), complementing the
      information obtained in the clinical evaluation.

PMID- 20158955
TI  - Amelioration of rCBF and PbtO2 following TBI at high altitude by hyperbaric
      oxygen pre-conditioning.
AB  - OBJECTIVES: Hypobaric hypoxia at high altitude can lead to brain damage and pre
      conditioning with hyperbaric oxygen (HBO) can reduce ischemic/hypoxic brain
      injury. This study investigates the effects of high altitude on traumatic brain
      injury (TBI) and examines the neuroprotection provided by HBO preconditioning
      against TBI. METHODS: Rats were randomly divided into four groups: HBO pre
      conditioning group (HBOP, n=10), high altitude group (HA, n=10), plain control
      group (PC, n=10) and plain sham operation group (sham, n=10). All groups were
      subjected to head trauma by weight drop device except for the sham group. Rats
      from each group were examined for neurological function, regional cerebral blood
      flow (rCBF) and brain tissue oxygen pressure (PbtO(2)) and were killed for
      analysis by transmission electron microscope. RESULTS: The score of neurological
      deficits in the HA group was highest, followed by the HBOP group and the PC
      group, respectively. Both rCBF and PbtO(2) were the lowest in the HA group. Brain
      morphology and structure seen via the transmission electron microscope was
      diminished in the HA group, while fewer pathological injuries occurred in the
      HBOP and PC groups. CONCLUSIONS: High altitude aggravates TBI significantly and
      HBO pre-conditioning can attenuate TBI in rats at high altitude by improvement of
      rCBF and PbtO(2). Pre-treatment with HBO might be beneficial for people traveling
      to high altitude locations.

PMID- 20158956
TI  - Food access, availability, and affordability in 3 Los Angeles communities,
      Project CAFE, 2004-2006.
AB  - INTRODUCTION: Racial/ethnic minority communities are at increasingly high risk
      for chronic diseases related to obesity. Access to stores that sell affordable,
      nutritious food is a prerequisite for adopting a healthful diet. The objective of
      this study was to evaluate food access, availability, and affordability in 3
      nonoverlapping but similar low-income communities in urban Los Angeles,
      California. METHODS: Using a community-based participatory research approach, we
      trained community members to conduct a food assessment to 1) map the number and
      type of retail food outlets in a defined area and 2) survey a sample of stores to
      determine whether they sold selected healthful foods and how much those foods
      cost. We used descriptive statistics to summarize findings. RESULTS: Of the 1,273
      food establishments mapped in the 3 neighborhoods, 1,023 met the criteria of
      "retail food outlet." The most common types of retail food outlets were fast-food
      restaurants (30%) and convenience/liquor/corner stores (22%). Supermarkets made
      up less than 2% of the total. Convenience/liquor/corner stores offered fewer than
      half of the selected healthful foods and sold healthful foods at higher prices
      than did supermarkets. CONCLUSION: Access to stores that sell affordable
      healthful food is a problem in urban Los Angeles communities. Healthful food
      strategies should focus on changing food environments to improve overall
      community health.

PMID- 20158957
TI  - Family history of lung cancer and contemplation of smoking cessation.
AB  - BACKGROUND: The prevalence of cigarette smoking in the United States has
      decreased, but current rates remain above nationally set objectives. A family
      history of lung cancer may motivate adult smokers to quit and contribute to
      further reductions in smoking prevalence. METHODS: We surveyed adult smokers (N =
      838) interviewed as part of the 2005 Health Information National Trends Survey.
      We examined the association between family history of lung cancer and smoking
      cessation precontemplation (not considering), contemplation (considering), and
      preparation. RESULTS: More people who reported a family history of lung cancer
      were in contemplation/preparation stages (41%) than were in the precontemplation
      stage (19%). Adults who reported a family history of lung cancer were more likely
      (odds ratio 2.55 [95% confidence interval, 1.44-4.52]) to be contemplators than
      precontemplators after adjusting for demographic variables and level of daily
      smoking. CONCLUSION: Family history of lung cancer among adult smokers may be
      associated with contemplating quitting smoking. Further investigation of family
      history's role in bolstering motivation to quit smoking may assist in developing
      or improving smoking cessation interventions for this group.

PMID- 20158958
TI  - Perceptions of cardiovascular health in underserved communities.
AB  - INTRODUCTION: Cardiovascular disease is the leading cause of deaths and illnesses
      in US adults, and the prevalence is disproportionately high in underserved
      populations. In this study, we assessed respondents' understanding of context
      specific differences in knowledge and perceptions of disease, risk, and
      prevention in 6 underserved communities, with the longer-term goal of developing
      appropriate interventions. METHODS: Thirty-nine small-group sessions and 14
      interviews yielded data from 318 adults. Each site's researchers coded, analyzed,
      and extracted key themes from local data. Investigators from all sites
      synthesized results and identified common themes and differences. RESULTS: Themes
      clustered in 3 areas (barriers to cardiovascular health, constraints related to
      multiple roles, and suggestions for effective communications and programs).
      Barriers spanned individual, social and cultural, and environmental levels; women
      in particular cited multiple roles (eg, competing demands, lack of self-care).
      Programmatic suggestions included the following: personal, interactive, social
      context; information in language that people use; activities built around
      cultural values and interests; and community orientation. In addition,
      respondents preferred health-related information from trusted groups (eg, AARP),
      health care providers (but with noticeable differences of opinion), family and
      friends, and printed materials. CONCLUSION: Interventions to decrease barriers to
      cardiovascular health are needed; these strategies should include family and
      community context, small groups, interactive methods, culturally sensitive
      materials, and trusted information sources. New-immigrant communities need
      culturally and linguistically tailored education before receiving more
      substantive interventions.

PMID- 20158959
TI  - Profiles of 800,000 users of the National Cancer Institute's Cancer Information
      Service since the debut of online assistance, 2003-2008.
AB  - INTRODUCTION: In 2002, the Cancer Information Service (CIS) of the National
      Cancer Institute added to its toll-free telephone number 2 choices of media for
      access to cancer information specialists: e-mail and a proprietary online instant
      messaging service called LiveHelp. We sought to determine how new media users
      differ from telephone callers and the US population in general. METHODS: During
      the 6 years since the new media were added, we collected data from more than
      800,000 people who contacted CIS. RESULTS: Telephone calls to CIS declined while
      the number of LiveHelp and e-mail inquiries steadily increased. People who
      contacted CIS by telephone and LiveHelp were predominantly white and female and,
      compared with the general population, were relatively well educated. LiveHelp
      users were significantly younger, more educated, and more affluent than telephone
      callers. CIS clients asked most frequently for general cancer site information,
      information about treatment and side effects management, screening programs, and
      economic assistance. Telephone callers most often asked about breast cancer.
      CONCLUSION: The Internet has introduced new sources of health information and
      possibly a new type of health information seeker. With LiveHelp and e-mail, CIS
      is poised to meet the needs of the digital health consumer and also the
      traditional telephone caller.

PMID- 20158960
TI  - Cognitive health messages in popular women's and men's magazines, 2006-2007.
AB  - INTRODUCTION: Growing evidence suggests that physical activity, healthy diets,
      and social engagement may promote cognitive health. Popular media helps establish
      the public health agenda. In this study, we describe articles about cognitive
      health in top-circulating women's and men's magazines. METHODS: To identify
      articles on cognitive health, we manually searched all pages of 4 top-circulating
      women's magazines and 4 top-circulating men's magazines published in 2006 and
      2007 to identify articles on cognitive health. We examined article volume,
      narrative and illustrative content, information sources, and contact resources.
      RESULTS: Women's magazines had 27 cognitive health articles (5.32/1,000 pages),
      and men's magazines had 26 (5.26/1,000 pages). Diet was the primary focus (>75%
      of content) in 30% of articles in women's magazines and 27% of men's magazines.
      Vitamins/supplements were the focus of 15% of articles in men's magazines and 11%
      in women's magazines. Articles mentioned physical activity, cognitive activity,
      and social interaction, although these subjects were rarely the focus. Articles
      focused more on prevention than treatment. Topics were primarily "staying sharp,"
      memory, and Alzheimer's disease. Colleges/universities were most often cited as
      sources; contacts for further information were rare. Most articles were
      illustrated. DISCUSSION: Although the volume of cognitive health articles was
      similar in the magazines, content differed. More articles in men's magazines
      discussed multiple chronic conditions (eg, Alzheimer's disease), whereas more in
      women's magazines discussed memory. Including more articles that focus on
      physical activity and direct readers to credible resources could enhance the
      quality of cognitive health communication in the popular media.

PMID- 20158961
TI  - Comparison of small-area analysis techniques for estimating prevalence by race.
AB  - INTRODUCTION: The Behavioral Risk Factor Surveillance System (BRFSS) is commonly
      used for estimating the prevalence of chronic disease. One limitation of the
      BRFSS is that valid estimates can only be obtained for states and larger
      geographic regions. Limited health data are available on the county level and,
      thus, many have used small-area analysis techniques to estimate the prevalence of
      disease on the county level using BRFSS data. METHODS: This study compared the
      validity and precision of 4 small-area analysis techniques for estimating the
      prevalence of 3 chronic diseases (asthma, diabetes, and hypertension) by race on
      the county level. County-level reference estimates obtained through local data
      collection were compared with prevalence estimates produced by direct estimation,
      synthetic estimation, spatial data smoothing, and regression. Discrepancy
      statistics used were Pearson and Spearman correlation coefficients, mean square
      error, mean absolute difference, mean relative absolute difference, and rank
      statistics. RESULTS: The regression method produced estimates of the prevalence
      of chronic disease by race on the county level that had the smallest
      discrepancies for a large number of counties. CONCLUSION: Regression is the
      preferable method when applying small-area analysis techniques to obtain county
      level prevalence estimates of chronic disease by race using a single year of
      BRFSS data.

PMID- 20158962
TI  - A new public health tool for risk assessment of abnormal glucose levels.
AB  - INTRODUCTION: Self-reported prediabetes and diabetes rates underestimate true
      prevalence, but mass laboratory screening is generally impractical for risk
      assessment and surveillance. We developed the Abnormal Glucose Risk Assessment-6
      (AGRA-6) tool to address this problem. METHODS: Self-report data were obtained
      from the 1,887 adults (18 years or older) in the National Health and Nutrition
      Examination Survey (NHANES) 2005-2006 with fasting plasma glucose and oral
      glucose tolerance tests. We created AGRA-6 models by using logistic regression.
      Performance was validated with NHANES 2005-2006 data by using leave-1-out cross
      validation. Standard performance characteristics (sensitivity, specificity,
      predictive values, area under receiver-operating characteristic curves) were
      assessed, as was the potential efficiency of the models to reduce laboratory
      testing in screening efforts. RESULTS: Performance was good for all models under
      testing conditions. Use of the AGRA-6 in screening efforts could reduce
      laboratory testing by at least 30% when sensitivity is maximized and at least 52%
      when sensitivity and specificity are balanced. CONCLUSION: The AGRA-6 appears to
      be an effective, feasible tool that uses self-reported data compatible with the
      Behavioral Risk Factor Surveillance System to assess population-level prevalence,
      identify abnormal glucose levels, optimize screening efforts, and focus
      interventions to reduce the prevalence of abnormal glucose levels.

PMID- 20158963
TI  - Impact of a multimedia campaign to increase intention to call 9-1-1 for stroke
      symptoms, upstate New York, 2006-2007.
AB  - INTRODUCTION: Many people are not aware of stroke symptoms, the need for
      emergency care for those symptoms, and that calling 9-1-1 is recommended. The New
      York State Department of Health developed and implemented a multimedia campaign
      to increase stroke symptom awareness and awareness of the need to call 9-1-1.
      METHODS: The evaluation of the campaign's impact was a pre/post intervention
      matched comparison design. A random-digit-dialed list-assisted telephone survey
      was administered to measure reach of the campaign and change in intention to seek
      emergency care for stroke by calling 9-1-1 in response to 4 signs or symptoms.
      RESULTS: A larger proportion of respondents in the intervention region than in
      the comparison region reported seeing a stroke advertisement and reported the
      advertisement's message was to call 9-1-1. There was a significant increase
      between baseline and follow-up in intention to call 9-1-1 for the 4 stroke
      symptoms. These increases were greater in the intervention region than the
      comparison region. The differences between intervention and comparison groups in
      the increases in intention to call 9-1-1 ranged from 9% to 12% for specific
      stroke symptoms identified in oneself and from 4% to 12% for symptoms identified
      in another person. CONCLUSION: This multimedia campaign effectively increased
      intention to call 9-1-1 for stroke symptoms in the intervention region compared
      with a region matched for demographics and stroke rates. Multimedia campaigns are
      effective in increasing awareness of stroke symptoms and intention to immediately
      call 9-1-1.

PMID- 20158964
TI  - Changes in tobacco quitlines in the United States, 2005-2006.
AB  - INTRODUCTION: Telephone quitlines are an effective way to provide evidence-based
      tobacco dependence treatment services at the population level. Information about
      what services quitlines offer and how those services are used may improve their
      reach to the smoking population. METHODS: The North American Quitline Consortium
      surveyed state quitlines in 2005 and 2006 to get information about quitline
      services, funding, and use. We report changes between 2005 and 2006. RESULTS: By
      2006, all 50 states, the District of Columbia, and Puerto Rico had quitlines, and
      annual mean reach was approximately 1% of US adult smokers (aged 18 years or
      older). Significant increases were seen in mean quitline reach, mean per capita
      funding for quitline services, and provision of free cessation medications;
      otherwise, few changes were seen in quitline services. CONCLUSION: Quitlines have
      the potential to serve a large percentage of smokers. Between 2005 and 2006,
      gains in the number, reach, and per capita funding for quitline services in the
      United States were seen. Although this represents progress, further research and
      investment to optimize quitline service delivery and reach are required for
      quitlines to fulfill their potential of improving the health of the American
      population.

PMID- 20158965
TI  - Pedometer use among adults at high risk of type 2 diabetes, Finland, 2007-2008.
AB  - INTRODUCTION: A pedometer helps adults exercise more, but sedentary adults need
      instruction and advice to be motivated to use one. We conducted this qualitative
      study to describe the experiences of participants at high risk of type 2 diabetes
      who began using a pedometer. METHODS: A total of 74 people at high risk of type 2
      diabetes participated in 6 months of group counseling. From April 2007 to April
      2008, we collected data through questionnaires, theme interviews (n = 22) and
      video recordings of counseling sessions. From October 2007 through June 2008, we
      analyzed the data. RESULTS: Pedometers were useful tools for observing levels of
      exercise, setting personal goals for walking, and helping evaluate whether daily
      goals were met. Negative experiences were associated with functional failures,
      pedometers' unsuitability for exercise other than walking, and the goal of 10,000
      steps, which some participants considered too high. CONCLUSION: Sedentary adults
      can be motivated to use a pedometer if we inform them that regular users find it
      a useful instrument for increasing their level of exercise. These adults should
      set realistic goals for walking and receive adequate instructions for using
      pedometers.

PMID- 20158966
TI  - Health care costs and participation in a community-based health promotion program
      for older adults.
AB  - INTRODUCTION: EnhanceWellness (EW) is a community-based health promotion program
      that helps prevent disabilities and improves health and functioning in older
      adults. A previous randomized controlled trial demonstrated a decrease in
      inpatient use for EW participants but did not evaluate health care costs. We
      assessed the effect of EW participation on health care costs. METHODS: We
      performed a retrospective cohort study in King County, Washington. Enrollees in
      Group Health Cooperative (GHC), a mixed-model health maintenance organization,
      who were aged 65 years or older and who participated in EW from 1998 through 2005
      were matched 1:3 by age and sex to GHC enrollees who did not participate in EW.
      We matched 218 EW participants by age and sex to 654 nonparticipants.
      Participants were evaluated for 1 year after the date they began the program. The
      primary outcome was total health care costs; secondary outcomes were inpatient
      costs, primary care costs, percentage of hospitalizations, and number of hospital
      days. We compared postintervention outcomes between EW participants and
      nonparticipants by using linear regression. Results were adjusted for prior year
      costs (or health care use), comorbidity, and preventive health care-seeking
      behaviors. RESULTS: Mean age of participants and nonparticipants was 79 years,
      and 72% of participants and nonparticipants were female. Adjusted total costs in
      the year following the index date were $582 lower among EW participants than
      nonparticipants, but this difference was not significant. CONCLUSION: Although EW
      participation demonstrated health benefits, participation does not appear to
      result in significant health care cost savings among people receiving health care
      through a health maintenance organization.

PMID- 20158967
TI  - Perceptions about availability and adequacy of drinking water in a large
      California school district.
AB  - INTRODUCTION: Concerns about the influence of sugar-sweetened beverage
      consumption on obesity have led experts to recommend that water be freely
      available in schools. We explored perceptions about the adequacy of drinking
      water provision in a large California school district to develop policies and
      programs to encourage student water consumption. METHODS: From March to September
      2007, we used semistructured interviews to ask 26 California key stakeholders -
      including school administrators and staff, health and nutrition agency
      representatives, and families - about school drinking water accessibility;
      attitudes about, facilitators of, and barriers to drinking water provision; and
      ideas for increasing water consumption. Interviews were analyzed to determine
      common themes. RESULTS: Although stakeholders said that water was available from
      school drinking fountains, they expressed concerns about the appeal, taste,
      appearance, and safety of fountain water and worried about the affordability and
      environmental effect of bottled water sold in schools. Stakeholders supported
      efforts to improve free drinking water availability in schools, but perceived
      barriers (eg, cost) and mistaken beliefs that regulations and beverage contracts
      prohibit serving free water may prevent schools from doing so. Some schools
      provide water through cold-filtered water dispensers and self-serve water
      coolers. CONCLUSION: This is the first study to explore stakeholder perceptions
      about the adequacy of drinking water in US schools. Although limited in scope,
      our study suggests that water available in at least some schools may be
      inadequate. Collaborative efforts among schools, communities, and policy makers
      are needed to improve school drinking water provision.

PMID- 20158968
TI  - Disturbed sleep among adolescents living in 2 communities on the Texas-Mexico
      border, 2000-2003.
AB  - INTRODUCTION: Disturbed sleep is a public health problem, but few studies
      describe the prevalence of sleep problems among Hispanic adolescents. We
      estimated the prevalence of disturbed sleep and associated factors among ninth
      graders living on the Texas-Mexico border. METHODS: We used probabilistic
      sampling to conduct 2 cross-sectional, school-based surveys: 1 during the 2000
      2001 school year in the Lower Rio Grande Valley, Texas (n = 4,901), and 1 during
      the 2002-2003 school year in Matamoros, Tamaulipas, Mexico (n = 669). We assessed
      disturbed sleep during the 4 weeks before the survey. RESULTS: The prevalence of
      disturbed sleep in Matamoros was 36% and in the Lower Rio Grande Valley was 28%.
      Factors associated with disturbed sleep in both populations were smoking
      cigarettes, having ever used cocaine, having been forced to have sex, considering
      attempting suicide, feeling sad, and going without eating for 24 hours or more.
      CONCLUSION: This study revealed a high prevalence of disturbed sleep in high
      school students living on the Texas-Mexico border. This public health issue
      should be further investigated in both communities.

PMID- 20158969
TI  - Lack of choice in caregiving decision and caregiver risk of stress, North
      Carolina, 2005.
AB  - INTRODUCTION: An aspect of caregiving that has received little attention is the
      degree to which the choice to provide care affects a caregiver's emotional well
      being. We compared a population-based sample of informal caregivers who reported
      having a choice in caring with caregivers who did not have a choice in caring to
      determine the extent to which choice affects caregivers' self-reported stress.
      METHODS: We identified 341 informal caregivers who completed a caregiving module
      appended to the 2005 North Carolina Behavioral Risk Factor Surveillance System
      survey. We determined participants' self-reported stress by using a 5-point scale
      that was dichotomized and used adjusted binomial logistic regression to assess
      the risk of stress given lack of choice in caregiving. RESULTS: In the fully
      adjusted model, caregivers without a choice in caring were more than 3 times as
      likely to report stress as caregivers with a choice in caring. High level of
      burden also increased stress. Caregivers with no choice in caring were most
      commonly the primary caregiver of a parent. CONCLUSION: Caregivers who do not
      have a choice in caregiving were at increased risk of stress, which may
      predispose them to poor health outcomes. Further investigation is needed to
      determine whether interventions that target caregivers without a choice in caring
      can reduce their levels of stress.

PMID- 20158970
TI  - The GirlStars program: challenges to recruitment and retention in a physical
      activity and health education program for adolescent girls living in public
      housing.
AB  - BACKGROUND: Although physical inactivity is a concern for all adolescents,
      physical activity levels are especially low among minority adolescents and
      minimal among girls from low-income families. After-school programs can reduce
      high-risk behaviors and strengthen schools, families, and communities. CONTEXT:
      We conducted an operational research project that provided free access to a
      program of regular, organized physical activity combined with health education
      sessions for adolescent girls in 2 public housing developments in Boston,
      Massachusetts. METHODS: From July 2002 through October 2005, at each of 2 public
      housing sites, the GirlStars program participants met each week for two 2-hour
      sessions, 1 dedicated to physical activity and 1 dedicated to health education.
      Sessions were led by the project coordinator and a resident assistant at each
      development. OUTCOME: Participants in the GirlStars program increased their
      health knowledge, self-confidence, and decision-making skills, but rates of
      participation were low. Factors that affected participation included safety
      concerns, lack of community support for the program, interpersonal conflicts,
      attrition in staff, and conflicts with other activities. INTERPRETATION: Programs
      in public housing developments that address these barriers to recruitment and
      retention may be more successful and reach more girls.

PMID- 20158971
TI  - Availability, affordability, and accessibility of a healthful diet in a low
      income community, Central Falls, Rhode Island, 2007-2008.
AB  - BACKGROUND: Many Americans have diets that do not meet the dietary guidelines set
      by the US Department of Agriculture (USDA). Additionally, low-income people have
      the highest rates of obesity and have difficulty accessing the necessary foods
      for maintaining a healthful diet. CONTEXT: In December 2007 and January 2008, 21
      retail food stores in Central Falls, Rhode Island, where residents were
      predominantly low-income Hispanics, were evaluated for the availability and costs
      of foods that fulfill the USDA's Thrifty Food Plan (TFP) guidelines. METHODS:
      Each surveyed store was evaluated for variety and weekly cost of 3 different
      types of market baskets (2 families and an elder). Each store's proximity to
      public transportation was estimated by using geographic information systems
      mapping. OUTCOME: Only 2 stores in Central Falls and the discount supermarket in
      an adjacent city, Pawtucket, carried enough variety of foods to fill the TFP
      basket. At the 2 stores, costs were up to 40% higher, and at the discount store,
      costs were up to 18% cheaper, than the national average. Each of the stores was
      accessible by public transportation. INTERPRETATION: Meeting the USDA TFP
      guidelines is difficult in this low-income, predominantly Hispanic city. Although
      the components of the TFP are available, high prices may make a nutritious diet
      unaffordable.

PMID- 20158972
TI  - Designing competencies for chronic disease practice.
AB  - INTRODUCTION: Competencies are the cornerstone of effective public health
      practice, and practice specialties require competencies specific to their work.
      Although more than 30 specialty competency sets have been developed, a particular
      need remained to define competencies required of professionals who practice
      chronic disease prevention and control. To that end, the National Association of
      Chronic Disease Directors (NACDD) engaged a group of stakeholders in developing
      competencies for chronic disease practice. METHODS: Concept mapping was blended
      with document analysis of existing competencies in public health to develop a
      unique framework. Public health experts reviewed the results, providing extensive
      and richer understanding of the issues. RESULTS: The final product presents an
      integrated picture that highlights interrelationships among the specific skills
      and knowledge required for leading and managing state chronic disease programs.
      Those competencies fall into 7 clusters: 1) lead strategically, 2) manage people,
      3) manage programs and resources, 4) design and evaluate programs, 5) use public
      health science, 6) influence policies and systems change, and 7) build support.
      CONCLUSION: The project yielded a framework with a categorization scheme and
      language that reflects how chronic disease practitioners view their work,
      including integrating communications and cultural competency skills into relevant
      job functions. Influencing policies and systems change has distinct relevance to
      chronic disease practice. We suggest uses of the competencies in the field.

PMID- 20158973
TI  - A promotores de salud intervention to reduce cardiovascular disease risk in a
      high-risk Hispanic border population, 2005-2008.
AB  - INTRODUCTION: The high prevalence of cardiovascular disease (CVD) in the Hispanic
      population of the United States, together with low rates of health insurance
      coverage, suggest a potential cardiovascular health crisis. The objective of
      Project HEART (Health Education Awareness Research Team) was to promote behavior
      changes to decrease CVD risk factors in a high-risk Hispanic border population.
      METHODS: Project HEART took place from 2005 through 2008 as a randomized
      community trial with a community-based participatory research framework using
      promotores de salud (community health workers). A total of 328 participants with
      at least 1 CVD risk factor were selected by randomizing 10 US Census tracts in El
      Paso, Texas, to either the experimental or the control group. The experimental
      group (n = 192) was assigned to a series of 8 health classes using the Su
      Corazon, Su Vida curriculum. After 2 months of educational sessions, the group
      was followed for 2 months. The control group (n = 136) was given basic
      educational materials at baseline, and no other intervention was used. Main
      outcomes of interest included changes in health behaviors and clinical measures.
      RESULTS: Participants in the experimental group showed more awareness of CVD risk
      factors, more confidence in the control of these factors, and improved dietary
      habits (ie, lower salt and cholesterol intake, better weight-control practices)
      compared with the control group. Total cholesterol was 3% lower in the
      experimental than in the control participants, and nonhigh-density lipoprotein
      cholesterol and low-density lipoprotein cholesterol were both 5% lower.
      CONCLUSION: The HEART trial suggests that community health education using
      promotores de salud is a viable strategy for CVD risk reduction in a Hispanic
      border community.

PMID- 20158974
TI  - Asarone inhibits adipogenesis and stimulates lipolysis in 3T3-L1 adipocytes.
AB  - Asarone is a molecule found in certain plants such as Acorus calamus, the root of
      which is used in traditional medicine to treat diabetes. We determined the
      molecular mechanism underlying the anti-diabetic activity of asarone. Treatment
      of asarone significantly inhibited the differentiation of 3T3-L1 preadipocytes
      through suppression of expression of the transcription factors, CCAAT/enhancer
      binding protein-alpha and peroxisome proliferator activated receptor-gamma, which
      activate adipogenesis. Intracellular triglyceride levels were reduced by asarone
      in a dose-dependent manner and asarone treatment stimulated the phosphorylation
      of hormone-sensitive lipase. Together, the present findings indicate that asarone
      inhibits adipogenesis by down-regulation of PPARgamma and C/EBPalpha and reduces
      lipid accumulation by stimulation of lipolysis through an increase in hormone
      sensitive lipase activity.

PMID- 20158975
TI  - Effects of new Phoneutria spider toxins on glutamate release and [Ca2+]i in rat
      cortical synaptosomes.
AB  - Studies revealed that the venom of the Brazilian "armed" spider Phoneutria
      nigriventer contains potent neurotoxins that caused excitatory symptoms such as
      salivation, lachrymation, priapism, convulsions, flaccid and spastic paralysis.
      It was also reported that the main mechanism of action of those neurotoxins are
      effects on ion channels such as inhibition of the inactivation of Na+ channels,
      blockage of K+ channels and blockage of calcium channels. The venom from
      Phoneutria keyserlingi, as might be expected, contains a series of polypeptides
      that are very similar, but not identical, to the proteins previously obtained
      from the venom of P. nigriventer in terms of their amino acid sequences and
      biological activities. We evaluated the effects of some of the toxins of P.
      nigriventer and P. keyserlingi on glutamate release and the decrease in [Ca2+]i
      by using synaptosomes of rat brain cortices and fluorimetric assays. Sequence
      comparisons between the Phoneutria toxins of both the species showed great
      similarity in the location of cysteine residues. However, thus far, no
      pharmacological assays were performed to evaluate the extension of those
      biochemical modifications. Our results showed that differences between the amino
      acid sequences of Phoneutria toxins of both the species lead to the significant
      changes in the pharmacological properties of these toxins.

PMID- 20158976
TI  - Effects of glucose and advanced glycation end products on oxidative stress in
      MIN6 cells.
AB  - To explore the mechanism of oxidative stress induced by glucose and advanced
      glycation end products (AGEs) in MIN6 cells. The MIN6 cells were exposed to
      various concentrations of glucose or AGEs for some time, MTT assay was used to
      evaluate the cell viability, reactive oxygen species (ROS) was monitored using
      intracellular ROS capture Dihydroethidium (DHE) and dihydrorhodamine123 (DHR123).
      The signal was quantified using flow cytometry by measuring the mean fluorescent
      intensity (MFI). The NADPH oxidase activity was measured by chemiluminescence
      with lucigenin. Treatment of high glucose or AGEs decreased cell viability in a
      dose- and time- dependent fashion. Exposure of MIN6 cells to high glucose or AGEs
      significantly increased intracellular ROS production in a concentration- and time
      dependent manner. In parallel with the results of ROS production, the NADPH
      oxidase in MIN6 cells was activated due to increased glucose or AGEs
      concentration. High glucose and AGEs stimulated ROS production via the activation
      of NADPH oxidase. The oxidative stress may consequently impair pancreatic beta
      cell function and contribute to diabetes mellitus as a result.

PMID- 20158977
TI  - Effect of Solanum nigrum and Ricinus communis extracts on histamine and
      carrageenan-induced inflammation in the chicken skin.
AB  - We studied anti-inflammatory effect of ethanolic extract of Solanum nigrum leaves
      and Ricinus communis root bark using chicken skin as model. Leaves of these
      plants were dried under shade and powdered. 5% Ethanol extracts were prepared
      using Soxhlet and injected intraperitoneally (400 mg/kg) 1 hour prior to the
      induction of inflammation. Inflammatory lesion were induced by intradermal
      injection of 0.02 ml 0.05%w/v histamine (0-2 min, 15 min, 30 min, 1 hr and 6 hr)
      and 1% w/v carrageenan (0-2 min, 30 min, 1 hr, 6 hr, 12 hr and 48 hr) in
      different group of birds. Increase in vascular permeability was studied using
      Evans blue as a permeability marker both qualitatively and quantitatively.
      Cellular events were studied in skin lesions at various time intervals and cells
      were counted at high power objective under microscope. Both, extracts exhibited
      significant decrease in permeability response at an early stage (0-2 min) of
      histamine as well as in carrageenan induced inflammatory lesions. There was a
      significant (p< 0.05) suppression in the emigration of heterophils, monocytoid
      cells, basophils and total leukocytosis in Solanum nigrum and Ricinus communis
      pretreated chicken skin lesions as compared to the control. The present study
      suggested antihistamine and anti-inflammatory properties of ethanolic extract of
      Solanum nigrum and Ricinus communis.

PMID- 20158978
TI  - Microbiological and molecular investigation of an increase of human listeriosis
      in Belgium, 2006-2007.
AB  - In Belgium, the majority of cases of listeriosis are sporadic cases. In this
      study we present evidence for an episode of listeriosis: a time-linked cluster of
      cases that occurred in 2006 and 2007, and the identification of identical
      strains. The episode involved 11 patients, infected with Listeria monocytogenes
      of serovar 4b. The source of infection was not detected.

PMID- 20158979
TI  - Household transmissibility and other characteristics of seasonal oseltamivir
      resistant influenza A(H1N1) viruses, Germany, 2007-8.
AB  - During the influenza season 2007-8, the proportion of seasonal influenza A(H1N1)
      viruses resistant to the neuraminidase inhibitor oseltamivir increased worldwide.
      We conducted an investigation to compare patients infected with oseltamivir
      resistant (ose-R) and oseltamivir- susceptible (ose-S) influenza A(H1N1) viruses
      regarding risk factors for resistance and the capability to transmit in the
      household setting. Within a cohort of 396 laboratory confirmed influenza patients
      from sentinel physicians we conducted a nested case-control study among patients
      infected with A(H1N1). Thirty patients in the cohort were infected with influenza
      B, none with influenza A(H3N2) and 366 with A(H1N1). Of the 366 A(H1N1) viruses
      52 (14%) were ose-R. Demographic characteristics, oseltamivir exposure, travel
      history and outcome were not significantly different between ose-S and ose-R
      patients. Among 133 households in the nested case-control study, secondary
      household attack rates in households with ose-R cases and households with ose-S
      cases were similar (23 versus 26%; p-value=0.54). Ose-R household status and
      occurrence of secondary cases were associated with an odds ratio of 0.85 (95%
      confidence interval 0.38-1.88). We conclude that seasonal ose-R influenza A(H1N1)
      viruses have transmitted well in the household setting.

PMID- 20158980
TI  - Low acceptance of vaccination against the 2009 pandemic influenza A(H1N1) among
      healthcare workers in Greece.
AB  - A questionnaire survey on the attitude of healthcare workers towards pandemic
      influenza vaccination showed low acceptance (17%) of the pandemic vaccine.
      Factors associated with vaccine uptake were acceptance of seasonal influenza
      vaccination, medical profession and age. The main reason for refusal of
      vaccination was fear of side effects, which was stronger in those who received
      information on the safety of the vaccine mainly from mass media.

PMID- 20158981
TI  - Impact of the 2009 influenza A(H1N1) pandemic wave on the pattern of hibernal
      respiratory virus epidemics, France, 2009.
AB  - This short report based on clinical surveillance and laboratory data describes
      the circulation of rhinoviruses, influenza viruses and respiratory syncytial
      viruses (RSV) in France during the 2009-10 season compared with the previous
      winter season. The delayed circulation of RSV observed in 2009-10 compared with
      2008-09 suggests that the early circulation of the 2009 pandemic influenza
      A(H1N1) viruses had an impact on the RSV epidemic.

PMID- 20158982
TI  - Outbreaks of gastroenteritis linked to lettuce, Denmark, January 2010.
AB  - At least 11 linked outbreaks of gastroenteritis with a total of 260 cases have
      occurred in Denmark in mid January 2010. Investigations showed that the outbreaks
      were caused by norovirus of several genotypes and by enterotoxigenic Escherichia
      coli. Lettuce of the lollo bionda type grown in France was found to be the
      vehicle.

PMID- 20158983
TI  - The effect of the 2004 Italian law on outcomes of assisted reproduction
      technology in severe male factor infertility.
AB  - The Italian law regulating assisted reproductive technologies that came into
      force in 2004 restricts the number of fertilized oocytes per cycle to three,
      obliges the subsequent transfer of all resulting embryos and prohibits the
      freezing of surplus embryos. This study evaluates the impact of the law on severe
      oligozoospermic, cryptozoospermic, obstructive azoospermic and non-obstructive
      azoospermic patients. Intracytoplasmic sperm injection outcomes of 1066 cycles
      performed in the 4years before the passing of the law were compared with 804
      cycles performed in the 4years after the law came to pass. Globally, analysis of
      clinical and obstetric outcomes showed a significant decrease in terms of
      pregnancy and delivery rates per cycle (17.8% versus 10.9% and 14.2% versus 8.5%,
      respectively) and per embryo transfer (18.8% versus 13.8% and 15.0% versus 10.7%,
      respectively), and a significant drop in multiple deliveries (35.1% versus 17.6%)
      in the post-law period. Cryptozoospermic and azoospermic couples were affected by
      the Italian law more than severe oligozoospermic couples. The results showed that
      the Italian law limits the efficiency of assisted reproduction treatment in
      couples with severe male factor. It is hoped that the Italian assisted
      reproductive technologies law is altered as soon as possible, allowing the
      insemination of more than three oocytes.

PMID- 20158984
TI  - IVM and gene expression of sheep cumulus-oocyte complexes following different
      methods of vitrification.
AB  - To determine the optimal vitrification conditions for sheep cumulus-oocyte
      complexes (COC), good-quality isolated COC were randomly divided into non
      vitrified control, conventional straw, cryotop and solid-surface vitrification
      groups. In the conventional and cryotop methods, the vitrified COC were
      respectively loaded by conventional straw and cryotop, whereas in the solid
      surface group, the vitrified COC were loaded by cryotop and then cooled before
      plunging in liquid nitrogen. The results indicated that the mean percentage of
      viability of vitrified-warmed COC was higher in both cryotop groups than that of
      the conventional group (83.84+/-2.85 and 78.56+/-1.72 versus 63.43+/-1.48%,
      P<0.05). In the cryotop group, although the mean percentage of oocyte maturation
      was similar to that in the control group (48.81+/-3.09 versus 51.94+/-3.01%), it
      was significantly higher than the other vitrification groups (48.81+/-3.09 versus
      36.60+/-1.69 and 6.09+/-2.51%, respectively, P<0.05). However, the expression of
      maturation genes (GDF9, BMP15) was retarded after vitrification. Among the
      vitrification groups, the cryotop group had better expression. BMPRII was also
      expressed highly in the control, whereas ALK5 was similar in all groups. In
      conclusion, direct cryotop, when compared with other vitrification methods,
      seemed to be safe and could increase the viability, post-warming maturation and
      maturation-gene expression rates of sheep COC.

PMID- 20158985
TI  - Akt expression in mouse oocytes matured in vivo and in vitro.
AB  - To improve developmental competence of in vitro matured oocytes, culture medium
      can be supplemented with hypoxanthine (Hx) and FSH or epidermal growth factor
      (EGF) to trigger the activation of essential signalling pathways regulating
      meiotic resumption and progression. Since the serine/threonine kinase, Akt,
      contributes to the regulation of the meiotic cell cycle, this study analysed its
      expression level and localization at the meiotic spindle in oocytes matured in
      vivo or in vitro in the presence of Hx-FSH or Hx-EGF. Independently of culture
      conditions adopted, Akt mRNA concentration did not vary from germinal vesicle to
      metaphase I (MI), while at MII a significant decrease in Akt1 mRNA concentration
      was recorded in oocytes matured in vivo and in those stimulated by Hx-EGF (P <
      0.05). Phoshorylated Akt protein content was similar in the different groups of
      MI oocytes, but it decreased at MII in oocytes matured either in vivo or in vitro
      with Hx-EGF. Ser-473-phosphorylated Akt was localized uniformly to the meiotic
      spindle in more than 90% of oocytes. These results indicate that, in mouse
      oocytes, Akt expression is differentially regulated during in vivo and in vitro
      maturation and suggest that EGF could be a positive modulator, even stronger than
      FSH, of oocyte meiotic maturation.

PMID- 20158986
TI  - Anti-Mullerian hormone testing is useful for individualization of stimulation
      protocols in oocyte donors.
AB  - While the age of a donor is a fundamental factor to the success of donor IVF, no
      serum markers have been demonstrated to be useful in predicting variability of
      ovarian response in individual donors. Anti-Mullerian hormone (AMH) has been
      described as an accurate marker of ovarian response in patients undergoing IVF,
      but has not been applied to oocyte donors. AMH concentrations from 104 anonymous
      oocyte donors between the ages of 21-32 years were studied and IVF outcome
      parameters compared. AMH was correlated with several parameters including the
      number of oocytes retrieved (r=0.232, P=0.024), the peak oestradiol
      concentrations (r=0.235, P=0.024) and the need to decrease gonadotrophin dose in
      order to avoid ovarian hyperstimulation syndrome (r=0.274, P=0.007). Receiver
      operating curve analysis was able to identify an AMH threshold that rendered
      about 70% sensitivity and 70% specificity for predicting the need to decrease
      gonadotrophin dosing. The clinical pregnancy rate was 77% per recipient and was
      not related to the donors' AMH concentrations. For oocyte donors, measurement of
      AMH appears most useful for determining gonadotrophin sensitivity in order to
      mitigate symptoms consistent with ovarian hyperstimulation.

PMID- 20158987
TI  - Ovarian function 6 years after cryopreservation and transplantation of whole
      sheep ovaries.
AB  - Whole ovary cryopreservation and transplantation has been proposed as a method
      for preserving long-term ovarian function. This work reports ovarian function
      6years post transplantation of frozen-thawed whole sheep ovaries. Three 9-month
      old Assaf sheep underwent unilateral oophorectomy to provide organs for the
      experiments. After perfusing with cold University of Wisconsin solution
      supplemented with 10% dimethyl sulphoxide, ovaries were cryopreserved using
      unidirectional solidification freezing technology. After thawing, ovaries were re
      perfused and re-transplanted orthotopically by microvascular re-anastomosis, to
      the contralateral ovarian pedicle after removing the remaining ovary. Six years
      following transplantation and after inducing superovulation, the sheep were
      killed and the ovaries analysed. Two ovaries had normal size and shape showing
      some recent corpora lutea, while the third showed atrophic changes. A total of 36
      antral follicles were counted by transillumination and four germinal vesicle
      oocytes were aspirated and matured in vitro to metaphase II. Serum progesterone
      concentrations were indicative of ovulatory activity in one of the three sheep.
      Histological evaluations revealed normal tissue architecture, intact blood
      vessels and follicles at various stages. Currently, this is the longest recorded
      ovarian function after cryopreservation and re-transplantation. Cryopreservation
      of whole ovaries, using directional freezing combined with microvascular
      anastomosis, is a promising method for preserving long-term reproductive capacity
      and endocrine function.

PMID- 20158988
TI  - GPR3 may not be a potential candidate gene for premature ovarian failure.
AB  - The G protein-coupled receptor gene GPR3 is expressed predominantly in oocytes,
      and functions in the early development of oocytes in the ovarian follicle. GPR3
      is essential for meiotic arrest maintenance in mice, which makes it a candidate
      gene for premature ovarian failure (POF). The coding region of GPR3 was screened
      in 100 Chinese POF patients for variants of the GPR3 gene. Except for one novel
      variant in the 3'UTR region in three subjects and another novel synonymous c.135G
      ->A variant in one subject, no perturbations were found in the coding region. The
      results of this study suggested that mutations in GPR3 are not a common cause of
      POF in Chinese women.

PMID- 20158989
TI  - Failed fertilization after clinical intracytoplasmic sperm injection.
AB  - Intracytoplasmic sperm injection (ICSI) has resulted in pregnancy and birth for
      many couples, including those with severe male factor infertility. However, even
      after ICSI, complete failure of fertilization occurs in 1-3% of cycles. Most
      cases occur due to low number of mature oocytes, failure of oocyte activation or
      non-availability of appropriate spermatozoa for injection. Given the significant
      emotional and financial involvement in assisted reproductive cycles, failure of
      fertilization in all mature oocytes is a distressful event. It is not
      predictable. Since follow-up ICSI cycles result in fertilization in 85% of cases,
      repeated ICSI attempts are suggested. Physicians should counsel patients
      experiencing repeated failure of fertilization after ICSI cycles about available
      options including donated oocytes/embryos, donor sperm insemination, adoption or
      remaining childless if these choices are not acceptable due to religious or
      ethical reasons. This review discusses the causes and remedies for failed
      fertilization after clinical ICSI.

PMID- 20158990
TI  - External quality control for embryology laboratories.
AB  - Participation in external quality control (EQC) programmes is recommended by
      various scientific societies. Results from an EQC programme for embryology
      laboratories are presented. This 5-year programme consisted of the annual
      delivery of (i) materials to test toxicity and (ii) a DVD/CD-ROM with images of
      zygotes and embryos on days 2 and 3, on the basis of which the participants were
      asked to judge the embryo quality and to take a clinical decision. A high degree
      of agreement was considered achieved when over 75% of the laboratories produced
      similar classifications. With respect to the materials analysed, the specificity
      was 68% and the sensitivity was 83%. Concerning embryo classification, the
      proportion of embryos on which a high degree of agreement was achieved increased
      during this period from 35% to 55%. No improvement was observed in the degree of
      agreement on the clinical decision to be taken. Day-3 embryos produced a higher
      degree of agreement (58%) than did day-2 embryos (32%) (P<0.05). Participation in
      EQC increased the degree of inter-laboratory agreement on embryo classification,
      but not the corresponding agreement on clinical decision taking. It is necessary
      to introduce measures aimed at standardizing decision taking procedures in
      embryology laboratories.

PMID- 20158991
TI  - Development of a real-time PCR method for rapid sexing of human preimplantation
      embryos.
AB  - Genes on the X chromosome are known to be responsible for more than 200
      hereditary diseases. After IVF, the simple selection of embryo sex before uterine
      transfer can prevent the occurrence of affected offspring among couples at risk
      for these genetic disorders. The aim of this investigation was to develop a rapid
      method of preimplantation genetic diagnosis (PGD) using real-time polymerase
      chain reaction (PCR) for the sexing of human embryos, and to compare it to the
      fluorescence in-situ hybridization technique, considered to be the gold standard.
      After biopsies were obtained from 40 surplus non-viable embryos for transfer, a
      total of 98 blastomeres were analysed. It was possible to analyse 24 embryos
      (60%) by both techniques, generating a total of 70 blastomeres (35 per
      technique), while 28 blastomeres from 16 embryos (40%) were analysed only by real
      time PCR. A rapid and safe method was developed in the present study for the
      sexual diagnosis of a single human cell (blastomere and buccal cell) using the
      emerging technology of real-time PCR.

PMID- 20158992
TI  - Psychological impact of preimplantation genetic diagnosis: a review of the
      literature.
AB  - Preimplantation genetic diagnosis (PGD) was first reported as successful in
      humans in the early 1990s and nearly two decades later the psychological impact
      of PGD has not yet been clearly defined. As PGD requires the use of IVF, this
      paper provides a brief summary of literature related to the various psychological
      aspects of IVF followed by a review of the literature related to the
      psychological and broader psychosocial impact of PGD. The current literature
      includes attitudinal studies of couples for whom PGD may be beneficial and
      results suggest that those with traumatic reproductive and genetic histories are
      more likely to find PGD an acceptable treatment option. A small number of studies
      have used samples of women and couples who have used PGD. Due to a general lack
      of homogeneity in scope, method and results, these studies have not provided a
      uniform understanding of the PGD experience. Promisingly, however, two studies on
      parents of children born after PGD that explored parental stress show no
      differences between PGD, IVF and natural conception couples. The paper concludes
      that the missing link in the literature is a prospective study of PGD using
      validated psychological scales. Suggestions for future research are provided.

PMID- 20158993
TI  - Improved detection of aneuploid blastocysts using a new 12-chromosome FISH test.
AB  - Fluorescence in-situ hybridization (FISH) has been the principal method used for
      the identification and preferential transfer of chromosomally normal embryos, in
      the context of both preimplantation genetic diagnosis (PGD) and screening (PGS).
      Generally, the probe combinations used during PGS have focused on chromosomes
      frequently identified as abnormal in prenatal samples or material derived from
      first-trimester spontaneous abortions. Recent data, however, obtained with the
      use of comparative genomic hybridization (CGH), have suggested that commonly used
      PGS strategies may fail to detect a large number of aneuploidies affecting
      preimplantation embryos. Some chromosomes, which have been relatively neglected
      in PGS protocols thus far, display a disproportionate contribution to embryo
      aneuploidy and should be prioritized for screening. Using CGH data, it is
      possible to design new probe combinations that examine between 10 and 12
      chromosomes and are capable of accurately diagnosing 89-91% of anomalies seen in
      embryos. At present, 24-chromosome tests, such as CGH, array CGH or single
      nucleotide polymorphism arrays, remain relatively costly and, in some cases, are
      yet to be fully validated. For these reasons, a cost-effective method, capable of
      accurately detecting almost all aneuploid embryos, represents an attractive
      alternative to comprehensive chromosome screening approaches.

PMID- 20158994
TI  - Cord blood: the future of regenerative medicine?
AB  - Cord blood stem cells have been in routine clinical practice for the past 20
      years. The development of new therapeutic protocols in regenerative medicine
      require the use of stem cells and umbilical cord blood is an important and
      readily available source of cells for these applications. The latest concepts in
      routine transplantation of cord blood are reviewed followed by the critical role
      of cord blood stem cells in regenerative medicine research and novel approaches
      using cord blood as a source of whole blood for transfusion.

PMID- 20158995
TI  - Dual action microbicides: reappraisal of their roles in contraceptive research.
AB  - Of the variety of contraceptive options available for women, very few provide
      dual protection against sexually transmitted diseases. Due to increased incidence
      of human immunodeficiency virus type 1 (HIV-1), genital herpes, hepatitis B and
      human papilloma virus, development of novel contraceptive strategies that
      incorporate antiviral activity has become the top priority in contraceptive
      research. Topical microbicides are now considered to be the last ray of hope, as
      they would ideally provide protection against unwanted pregnancy, proper
      lubrication during sexual activity, and preclude the vaginal/rectal transmission
      of sexually transmitted diseases. A large number of vaginal microbicides are in
      the preclinical or clinical stages of evaluation for their safety, efficacy and
      acceptability. However, a major bottleneck in the development of novel mechanism
      based dual microbicides has been their detergent-like effects, along with
      debilitating action on the vaginal microflora. Hence the search is still on for
      the ideal dual microbicide/s that may obliterate these disadvantages and provide
      an invincible shield to women in their crusade against unintended pregnancy as
      well as sexually transmitted diseases. The present review highlights the current
      scenario towards the development of novel contraceptive strategies to counteract
      the rampant spread of sexually transmitted diseases, with special reference to
      HIV/AIDS.

PMID- 20158996
TI  - Sperm chromatin structure assay and classical semen parameters: systematic
      review.
AB  - The present study is based on a PubMed search and compares the clinical validity
      of classical semen parameters (CSP) and the sperm chromatin structure assay
      (SCSA) in different clinical contexts. The PubMed database was searched using
      keywords on the sperm diagnostic test for pregnancy in three clinical scenarios:
      (i) couples attempting to conceive; (ii) couples who had been attempting to
      conceive for 12months without success; and (iii) couples treated with
      intrauterine insemination (IUI). There was a considerable heterogeneity among the
      studies included. For couples attempting to conceive following a SCSA that
      produced an abnormal result, the likelihood of male factor infertility ranged
      from a pre-test value of 7.5% to a post-test value of 32.1% [95% confidence
      interval (CI) 15.7-54.5], while after CSP with an abnormal result, the post-test
      probability was 17.3% (95% CI 11.8-24.5). For a pre-test prevalence of male
      factor infertility of 50%, the post-test probability of male factor infertility
      after an abnormal test is very similar for both SCSA and CSP. In couples treated
      with IUI, the clinical validity of SCSA is higher than that of sperm morphology
      alone, but not enough to introduce SCSA as a test in male infertility work-up.

PMID- 20158997
TI  - Variants in the Eppin gene show association with semen quality in Han-Chinese
      population.
AB  - The human epididymal protease inhibitor (Eppin) gene is specifically expressed in
      testis and epididymis and is important in male reproduction. However, to date,
      there is no report on variants of this gene, particularly in relation to male
      fertility. To investigate the association between Eppin genetic variants and
      semen quality, variant genotyping and semen analysis was performed in 473 males
      with definite idiopathic infertility by polymerase chain reaction-restriction
      fragment length polymorphism and computer-assisted semen analysis. It was found
      that rs6124715 GG/CG genotypes were associated with a significantly higher
      curvilinear velocity (VCL) (P=0.029 and 0.021 respectively) and average path
      velocity (VAP) (P=0.043 and 0.016 respectively) compared with the CC genotype.
      The straight line velocity (VSL) between rs6124715 CG and CC genotype was also
      significantly different (P=0.019). Regarding variant rs11594, subjects with C
      allele (CC or AC) had significantly lower VCL (P=0.011 and 0.046 respectively),
      VSL (P=0.025 and 0.041 respectively) and VAP (P=0.026 and 0.030 respectively) in
      comparison with AA homozygote. The sperm number per ejaculate was also
      significantly different between rs2231829 TT and CC genotype (P=0.042). These
      findings indicate, for the first time, that the genetic variants in the Eppin
      gene may be associated with semen quality.

PMID- 20158998
TI  - Sperm nuclear vacuoles, as assessed by motile sperm organellar morphological
      examination, are mostly of acrosomal origin.
AB  - Microinjection of nuclear vacuole-free spermatozoa selected by motile sperm
      organellar morphological examination (MSOME) has been claimed to enhance assisted
      reproduction treatment outcome compared with intracytoplasmic sperm injection.
      However, the nature of these nuclear vacuoles is unclear, since their
      localization at the front of the sperm head suggests they might be of acrosomal
      origin. To study this hypothesis, acrosomal status was evaluated using Pisum
      sativum agglutinin staining on a smear, together with sperm organellar
      morphological examination using the same optics as for MSOME on 30 sperm samples
      from infertile patients, yielding >3200 spermatozoa. Vacuoles were present in 61%
      of spermatozoa when acrosomal material or intact acrosomes were observed, versus
      29% when spermatozoa were acrosome reacted (P<0.0001). Induction of the acrosomal
      reaction by ionophore A23587 from 17.4% to 36.1% significantly increased the
      percentage of vacuole-free spermatozoa from 41.2% to 63.8% (P<0.001). These data
      suggest that most nuclear vacuoles are of acrosomal origin. Hence, the best
      spermatozoa selected by MSOME are mostly acrosome-reacted spermatozoa. As
      microinjection of spermatozoa with a persistent acrosome drastically hampers
      embryo development in animal models, this suggests that the improvement in
      pregnancy rates reported following intracytoplasmic injection of morphologically
      selected sperm might be due to the procedure allowing injection of acrosome
      reacted spermatozoa.

PMID- 20158999
TI  - Perturbations in finger length and digit ratio (2D:4D) in ICSI children.
AB  - Intracytoplasmic sperm injection (ICSI) is used to overcome severe male-factor
      infertility where males are azoospermic or have poor quality spermatozoa.
      Perturbations of finger length (short finger length adjusted for height and high
      second-to-fourth digit ratio, or 2D:4D) have been described in azoospermic men
      and men who are rated as having low sexual attractiveness. High 2D:4D has been
      described in women with high fecundity. Such perturbations may be related to
      endocrine regulation of some homeobox genes. This study compared finger length
      and 2D:4D in singleton children conceived with the help of ICSI with those in
      naturally conceived singleton controls. Participants were recruited from centres
      in Germany and the UK. There were 211 children conceived by ICSI and 195
      controls. Finger length was measured from photocopies of the ventral surface of
      the hand. In comparison to controls, male and female ICSI children had shorter
      fingers after correction for height. There was also evidence that female ICSI
      children may have higher 2D:4D than female controls. Perturbations in finger
      length in ICSI children may be inherited from their fathers and, in the case of
      boys, could be associated with lower fertility and reduced sexual attractiveness.
      For ICSI females, increased 2D:4D may be associated with increased fertility.

PMID- 20159000
TI  - Growth of children conceived by IVF and ICSI up to 12years of age.
AB  - Recent studies have given conflicting results regarding growth in children born
      following assisted reproductive treatments up to the age of 18years. It has been
      suggested that children conceived via IVF may be taller than naturally conceived
      children and that this may due to subtle epigenetic alteration of imprinted genes
      as a result of the IVF process. A prospective match-controlled study was
      performed to investigate the growth of children born in the UK following standard
      IVF and intracytoplasmic sperm injection (ICSI) up to the age of 12years. The
      study assessed 143 IVF and 166 ICSI children with 173 matched naturally conceived
      controls. Primary end-points were height and weight at various time points:
      birth, 5years, 7-9years and 10-12years. In addition, head circumference was
      assessed at birth. No significant differences were observed regarding head
      circumference, height and weight between the three groups at any of the time
      points. In conclusion, this preliminary study provides reassuring information
      regarding the growth of IVF and ICSI children up to 12years. Further studies must
      continue to investigate the growth and other outcomes in assisted-conception
      children as they develop through puberty into early adulthood.

PMID- 20159001
TI  - Visfatin and retinol-binding protein 4 concentrations in lean, glucose-tolerant
      women with PCOS.
AB  - Since insulin resistance is accepted to be a common feature of polycystic ovary
      syndrome (PCOS), the exact molecular mechanism(s) involved in glucose and lipid
      metabolism have been under investigation in the syndrome. Recently, two novel
      adipokines, namely visfatin and retinol-binding protein 4 (RBP4), have been
      suggested to play a role in insulin resistance and diabetes. This study sought to
      determine whether plasma concentrations of visfatin and RBP4 are altered in PCOS
      by comparing a total of 27 lean, normal glucose-tolerant PCOS patients with 19
      age- and body mass index-matched healthy controls. The mean plasma visfatin
      concentrations were higher in PCOS patients than those in healthy subjects
      (37.9+/-18.2 versus 19.8+/-17.5, P<0.01), while RBP4 concentrations were similar
      between the two. Both adipokines were correlated with each other in the whole
      (r=0.50, P<0.01) and in PCOS (r=0.52, P<0.01) groups but not in controls. The
      results suggest that lean, glucose-tolerant women with PCOS have increased
      circulating visfatin and unaltered RBP4 concentrations compared with healthy lean
      women. In order to clarify overlapping effects and their potential contribution
      to the pathophysiology of PCOS, further studies are needed.

PMID- 20159002
TI  - Modified natural cycle IVF and mild IVF: a 10 year Swedish experience.
AB  - Modified natural cycle IVF (mnc-IVF) or mild IVF (m-IVF) was offered to selected
      patients between 1996 and 2007; 43 patients during 129 cycles were treated with
      mnc-IVF and 145 couples during 250 cycles were treated with m-IVF. Comparison
      with outcome from conventional IVF cycles during the same time period and in the
      same clinic was performed. Although 53.5 and 39.6% of started cycles respectively
      never reached embryo transfer, the ongoing pregnancy rates per embryo transfer
      were 26.7% for mnc-IVF and 27.2% for m-IVF. During the same time period,
      cancellation rate for conventional IVF was 13.7% and the ongoing pregnancy rate
      per embryo transfer was 34.3%. For patients > or =38years of age, the ongoing
      pregnancy rate per embryo transfer was 17.5% in the m-IVF group. None of the
      patients aged > or =38years in the mnc-IVF group achieved an ongoing pregnancy.
      For patients treated with conventional IVF, the > or =38years of age pregnancy
      rate per embryo transfer was 27.0%. Costs of medication for m-IVF and mnc-IVF
      were 96.3 and 97.5% less than for the least expensive conventional IVF cycle
      respectively. Pregnancy rates per embryo transfer are acceptable for these
      treatment modalities, the cost for medication is low, risks for complications are
      dramatically reduced, and the treatments may be more psychologically acceptable
      to the patients.

PMID- 20159003
TI  - Single dose GnRH agonist administration in the luteal phase of assisted
      reproduction cycles: is the effect dependent on the type of GnRH analogue used
      for pituitary suppression?

PMID- 20159005
TI  - DNAzyme self-assembled gold nanoparticles for determination of metal ions using
      fluorescence anisotropy assay.
AB  - Gold nanoparticles can be exploited to facilitate a highly sensitive and
      selective metal ion detection based on fluorescence anisotropy assay with metal
      ion-dependent DNA-cleaving DNAzyme. This assay allows rapid and accurate
      determination of metal ions in aqueous medium at room temperature. The method has
      been demonstrated for determination of Cu(2+) and Pb(2+) ions. The detection
      sensitivity can be significantly improved to 1 nM by using a "nanoparticle
      enhancement" approach. Moreover, the assay was also tested in 384-well plates for
      high-throughput routine determination of toxic metal ions in environmental
      samples. The method showed distinct advantages over conventional methods in terms
      of its potential sensitivity, specificity, and ability for rapid response.

PMID- 20159006
TI  - Statistical significance analysis of nuclear magnetic resonance-based
      metabonomics data.
AB  - Use of nuclear magnetic resonance (NMR)-based metabonomics to search for human
      disease biomarkers is becoming increasingly common. For many researchers, the
      ultimate goal is translation from biomarker discovery to clinical application.
      Studies typically involve investigators from diverse educational and training
      backgrounds, including physicians, academic researchers, and clinical staff. In
      evaluating potential biomarkers, clinicians routinely use statistical
      significance testing language, whereas academicians typically use multivariate
      statistical analysis techniques that do not perform statistical significance
      evaluation. In this article, we outline an approach to integrate statistical
      significance testing with conventional principal components analysis data
      representation. A decision tree algorithm is introduced to select and apply
      appropriate statistical tests to loadings plot data, which are then heat map
      color-coded according to P score, enabling direct visual assessment of
      statistical significance. A multiple comparisons correction must be applied to
      determine P scores from which reliable inferences can be made. Knowledge of means
      and standard deviations of statistically significant buckets enabled computation
      of effect sizes and study sizes for a given statistical power. Methods were
      demonstrated using data from a previous study. Integrated metabonomics data
      assessment methodology should facilitate translation of NMR-based metabonomics
      discovery of human disease biomarkers to clinical use.

PMID- 20159008
TI  - Special issue composed of minireviews written by scientists from Karolinska
      Institutet to celebrate its 200-year anniversary. Preface.

PMID- 20159007
TI  - Recombinant expression, purification, and characterization of ThmD, the
      oxidoreductase component of tetrahydrofuran monooxygenase.
AB  - Tetrahydrofuran monooxygenase (Thm) catalyzes the NADH-and oxygen-dependent
      hydroxylation of tetrahydrofuran to 2-hydroxytetrahydrofuran. Thm is composed of
      a hydroxylase enzyme, a regulatory subunit, and an oxidoreductase named ThmD.
      ThmD was expressed in Escherichia coli as a fusion to maltose-binding protein
      (MBP) and isolated to homogeneity after removal of the MBP. Purified ThmD
      contains covalently bound FAD, [2Fe-2S] center, and was shown to use
      ferricyanide, cytochrome c, 2,6-dichloroindophenol, and to a lesser extent,
      oxygen as surrogate electron acceptors. ThmD displays 160-fold preference for
      NADH over NADPH and functions as a monomer. The flavin-binding domain of ThmD
      (ThmD-FD) was purified and characterized. ThmD-FD displayed similar activity as
      the full-length ThmD and showed a unique flavin spectrum with a major peak at
      463nm and a small peak at 396 nm. Computational modeling and mutagenesis analyses
      suggest a novel three-dimensional fold or covalent flavin attachment in ThmD.

PMID- 20159009
TI  - The relevance of ice crystal formation for the cryopreservation of tissues and
      organs.
AB  - This paper discusses the role of ice crystal formation in causing or contributing
      to the difficulties that have been encountered in attempts to develop effective
      methods for the cryopreservation of some tissues and all organs. It is shown that
      extracellular ice can be severely damaging but also that cells in situ in tissues
      can behave quite differently from similar cells in a suspension with respect to
      intracellular freezing. It is concluded that techniques that avoid the formation
      of ice altogether are most likely to yield effective methods for the
      cryopreservation of recalcitrant tissues and vascularised organs.

PMID- 20159010
TI  - Inflexin attenuates proinflammatory responses and nuclear factor-kappaB
      activation in LPS-treated microglia.
AB  - Activated microglia participate in neuroinflammation which contribute to neuronal
      damage. Suppression of microglial activation would have therapeutic benefits,
      which lead to alleviation of the progression of neurodegeneration. In this study,
      the inhibitory effects of inflexin, a putative antiinflammatory agent isolated
      from Isodon excisus (Max.) Kudo (Labiateae), on the production of proinflammatory
      mediators were investigated in the lipopolysaccharide (LPS)-stimulated microglia.
      Inflexin significantly inhibited the release of nitric oxide (NO). Consistently,
      both the mRNA and the protein levels for the inducible NO synthase were decreased
      by inflexin in a concentration-dependent manner. Inflexin also inhibited the
      expression of cyclooxygenase (COX)-2, but not the COX-1 and effectively reduced
      the LPS-induced expression of proinflammatory cytokines in a dose-dependent
      manner. Furthermore, inflexin inhibited the degradation of IkappaB-alpha and the
      activation of NF-kappaB, p65 and Akt, while the MAPKs signal pathway was not
      affected. Our data suggest that inflexin was able to suppress neuroinflammation
      via inhibition of NF-kappaB activation and Akt pathway indicating that inflexin
      may be developed as a potent therapeutic agent in treating neuroinflammatory
      diseases.

PMID- 20159011
TI  - Topical and intravenous pilocarpine stimulated accommodation in anesthetized
      rhesus monkeys.
AB  - Many studies have used pilocarpine to stimulate accommodation in both humans and
      monkeys. However, the concentrations of pilocarpine used and the methods of
      administration vary. In this study, three different methods of pilocarpine
      administration are evaluated for their effectiveness in stimulating accommodation
      in rhesus monkeys. Experiments were performed in 17 iridectomized, anesthetized
      rhesus monkeys aged 4-16 years. Maximum accommodation was stimulated in all these
      monkeys with a 2% pilocarpine solution maintained on the cornea for at least 30
      min in a specially designed perfusion lens. In subsequent topical pilocarpine
      experiments, baseline refraction was measured with a Hartinger coincidence
      refractometer and then while the monkeys were upright and facing forward,
      commercially available pilocarpine (2, 4, or 6%) was applied topically to the
      cornea as 2 or 4 drops in two applications or 6 drops in three applications over
      a five minute period with the eyelids closed between applications. Alternatively,
      while supine, 10-12 drops of pilocarpine were maintained on the cornea in a
      scleral cup for 5 min. Refraction measurements were begun 5 min after the second
      application of pilocarpine and continued for at least 30 min after initial
      administration until no further change in refraction occurred. In intravenous
      experiments, pilocarpine was given either as boluses ranging from 0.1mg/kg to
      2mg/kg or boluses followed by a constant infusion at rates between 3.06 mg/kg/h
      and 11.6 mg/kg/h. Constant 2% pilocarpine solution on the eye in the perfusion
      lens produced 10.88+/-2.73 D (mean+/-SD) of accommodation. Topically applied
      pilocarpine produced 3.81 D+/-2.41, 5.49 D+/-4.08, and 5.55 D+/-3.27 using 2%,
      4%, and 6% solutions respectively. When expressed as a percentage of the
      accommodative response amplitude obtained in the same monkey with constant 2%
      pilocarpine solution on the eye, the responses were 34.7% for 2% pilocarpine,
      48.4% for 4% pilocarpine, and 44.6% for 6% pilocarpine. Topical 4% and 6%
      pilocarpine achieved similar, variable accommodative responses, but neither
      achieved maximum accommodation. IV boluses of pilocarpine achieved near maximal
      levels of accommodation at least ten times faster than topical methods. Doses
      effective for producing maximum accommodation ranged from 0.25mg/kg to 1.0mg/kg.
      IV pilocarpine boluses caused an anterior movement of the anterior lens surface,
      a posterior movement of the posterior lens surface, and a slight net anterior
      movement of the entire lens. Considerable variability in response amplitude
      occurred and maximum accommodative amplitude was rarely achieved with topical
      application of a variety of concentrations of commercially available pilocarpine.
      Intravenous infusion of pilocarpine was a rapid and reliable method of producing
      a nearly maximal accommodative response and maintaining accommodation when
      desired.

PMID- 20159012
TI  - Trichomonas vaginalis: dehydroepiandrosterone sulfate and 17beta-estradiol alter
      NTPDase activity and gene expression.
AB  - We investigated the effect of dehydroepiandrosterone sulfate (DHEAS) and 17beta
      estradiol on NTPDase activity in fresh clinical (VP60) and long-term-grown (30236
      ATCC) isolates of Trichomonas vaginalis followed by NTPDase gene transcriptional
      analysis. ATP hydrolysis was activated in vitro by 17beta-estradiol (0.01
      1.0microM) in the VP60 isolate. Treatment for 2h with 17beta-estradiol (0.01
      1microM) promoted an inhibition in nucleotide hydrolysis in the 30236 isolate
      whereas the 12h-treatment promoted an activation of nucleotide hydrolysis in both
      isolates. ADP hydrolysis was inhibited in vitro by 1.0-5.0microM DHEAS in the
      ATCC isolate. The treatment with DHEAS (0.01-1.0microM) for 2h inhibited ATP and
      ADP hydrolysis in VP60; however, during a 12h-treatment with DHEAS, nucleotide
      hydrolysis was inhibited in both isolates. Two NTPDase orthologous (NTPDaseA and
      NTPDaseB) were identified and the treatment with DHEAS for 12h was able to
      inhibit mRNA NTPDaseA transcript levels from the VP60. These findings demonstrate
      that NTPDase activity and gene expression pattern are modulated by exposure to
      steroids in T. vaginalis.

PMID- 20159013
TI  - Interactions of antimicrobial peptides with Leishmania and trypanosomes and their
      functional role in host parasitism.
AB  - Antimicrobial peptides (AMPs) are multifunctional components of the innate
      systems of both insect and mammalian hosts of the pathogenic trypanosomatids
      Leishmania and Trypanosoma species. Structurally diverse AMPs from a wide range
      of organisms have in vitro activity against these parasites acting mainly to
      disrupt surface-membranes. In some cases AMPs also localize intracellularly to
      affect calcium levels, mitochondrial function and induce autophagy, necrosis and
      apoptosis. In this review we discuss the work done in the area of AMP
      interactions with trypanosomatid protozoa, propose potential targets of AMP
      activity at the cellular level and discuss how AMPs might influence parasite
      growth and differentiation in their hosts to determine the outcome of natural
      infection.

PMID- 20159014
TI  - Giardia duodenalis: kinetics of cyst elimination and the systemic humoral and
      intestinal secretory immune responses in gerbils (Meriones unguiculatus)
      experimentally infected.
AB  - This study aimed to determine the pre-patent period and to evaluate the kinetics
      of cyst elimination and the systemic humoral (IgA, IgG(1), IgG(2a), IgM, IgE) and
      intestinal secretory (IgA) immune responses in gerbils (Meriones unguiculatus)
      experimentally innoculated with different doses of Giardia duodenalis
      trophozoites. Forty-eight animals aged 6-8 weeks were used, equally distributed
      among six groups, five groups innoculated with different doses of trophozoites
      (10(1), 10(2), 10(3), 10(4), 10(5)) and one control (non-infected) group.
      Coproparasitological examinations were carried out daily up to 91 days after
      inoculation (d.a.i.) to determine the pre-patent period and the kinetics of cyst
      elimination. Blood and stool samples were weekly collected for antibody assays.
      The pre-patent period was observed from the 9 d.a.i. onwards, with intermittent
      elimination of variable quantities of cysts up to 27 d.a.i.. All infected
      gerbils, irrespective of the dose received, were able to mount systemic humoral
      immune responses as evidenced by specific IgM titers from 7 to 28 d.a.i.,
      corresponding to the peak of cyst elimination, followed by high and persistent
      IgG1 titers. Intestinal secretory responses were also seen with two peaks of
      fecal IgA titers, corresponding to IgM and IgG1 response peaks, respectively. In
      conclusion, systemic and intestinal humoral immune responses were related to the
      control of giardiasis in this experimental model.

PMID- 20159016
TI  - Regulation of ceramide channels by Bcl-2 family proteins.
AB  - Mitochondrial outer membrane permeabilization to proteins, an irreversible step
      in apoptosis by which critical proteins are released, is tightly regulated by Bcl
      2 family proteins. The exact nature of the release pathway is still undefined.
      Ceramide is an important sphingolipid, involved in various cellular processes
      including apoptosis. Here we describe the structural properties of ceramide
      channels and their regulation by the anti-apoptotic and pro-apoptotic proteins of
      the Bcl-2 family. The evolutionarily conserved regulation of ceramide channels by
      Bcl-2 family proteins, consistent with their role in apoptosis, lends credibility
      to the notion that ceramide channels constitute the protein release pathway.

PMID- 20159015
TI  - TPCs: Endolysosomal channels for Ca2+ mobilization from acidic organelles
      triggered by NAADP.
AB  - Two-pore channels (TPCs or TPCNs) are novel members of the large superfamily of
      voltage-gated cation channels with slightly higher sequence homology to the pore
      forming subunits of voltage-gated Ca(2+) and Na(+) channels than most other
      members. Recent studies demonstrate that TPCs locate to endosomes and lysosomes
      and form Ca(2+) release channels that respond to activation by the Ca(2+)
      mobilizing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). With
      multiple endolysosomal targeted NAADP receptors now identified, important new
      insights into the regulation of endolysosomal function in health and disease will
      therefore be unveiled.

PMID- 20159017
TI  - Recognition of cellooligosaccharides by a family 28 carbohydrate-binding module.
AB  - The crystal structures of a carbohydrate-binding module (CBM) family 28 domain of
      endoglucanase Cel5A from Clostridium josui have been determined in ligand-free
      and complex forms with cellobiose, cellotetraose, and cellopentaose as the first
      complex structures of this family. In the cleft of a beta-sandwich fold, the
      ligands are recognized by stacking interactions and hydrogen bonds. Conformations
      of the bound cellooligosaccharides are similar to those in crystals and solution
      but clearly different from the cellulose structure. Interestingly, the glucan
      chain bound on CBM28 is in the opposite direction of that bound to CBM17,
      although these families share significant structural similarity.

PMID- 20159019
TI  - Site-directed mutagenesis and PBAN activation of the Helicoverpa zea PBAN
      receptor.
AB  - Pheromone biosynthesis-activating neuropeptide (PBAN) and pyrokinins belong to a
      family of insect peptide hormones that have a common FXPRLamide C-terminal
      ending. The G-protein-coupled receptors (GPCRs) for this peptide family were
      first identified from a moth and Drosophila with sequence similarity to
      neuromedin U receptors from vertebrates. We have characterized the PBAN-receptor
      (PBAN-R or PR) active binding domains using chimeric GPCRs and proposed that
      extracellular loop 3 is critical for ligand selection. Here, we characterized the
      3rd extracellular domain of PBAN-R through site-directed point mutations. Results
      are discussed in context of the structural features required for receptor
      activation using receptor activation experiments and in silico computational
      modeling. This research will help in characterizing these receptors towards a
      goal of finding agonists and/or antagonists for PBAN/pyrokinin receptors.

PMID- 20159018
TI  - Identification and characterization of the novel protein CCDC106 that interacts
      with p53 and promotes its degradation.
AB  - The putative CCDC106 protein was previously identified as a p53-interacting
      partner by automated yeast two-hybrid screening, but its sequence and function
      have not been validated experimentally. Here, we identified three variant
      transcripts of the CCDC106 gene; these transcripts differ in their second exons
      due to the use of different splice acceptor site, but encode an identical protein
      of 280 residues. A bipartite nuclear localisation signal at residues 151-164
      mediates the nuclear localisation of CCDC106. Double immunofluorescence staining
      revealed the colocalisation of endogenous CCDC106 and p53 protein in nuclei. The
      in vivo interaction between CCDC106 and p53 was confirmed by a co
      immunoprecipitation assay. Furthermore, we demonstrated that CCDC106 promotes the
      degradation of p53 protein and inhibits its transactivity.

PMID- 20159020
TI  - GABAA receptor subunit beta1 is involved in the formation of protease-resistant
      prion protein in prion-infected neuroblastoma cells.
AB  - Gamma-aminobutyric acid type A (GABAA) receptor beta1 (gabrb1), a subunit of
      GABAA receptors involved in inhibitory effects on neurotransmission, was found to
      associate with the formation of protease-resistant prion protein in prion
      infected neuroblastoma cells. Silencing of gabrb1 gene expression significantly
      decreased the abnormal prion protein level but paradoxically increased the normal
      prion protein level. Treatment with a gabrb1-specific inhibitor, salicylidene
      salicylhydrazide, dose-dependently decreased the abnormal prion protein level,
      but silencing of other GABAA receptor subunits' gene expression and treatments
      with the receptor antagonists and agonists did not. Therefore, gabrb1 involvement
      in abnormal prion protein formation is independent of GABAA receptors.

PMID- 20159021
TI  - Prevalence, intensity, and aneuploidy patterns of disseminated neoplasia in
      cockles (Cerastoderma edule) from Arcachon Bay: seasonal variation and position
      in sediment.
AB  - The present report presents the first evidence of disseminated neoplasia (DN) in
      cockles Cerastoderma edule from Arcachon Bay (France). Aneuploidy of neoplastic
      cells allowed the use of flow cytometry (FCM) to diagnose and stage DN. A 1year
      survey (2007) of the prevalence and intensity (% of aneuploid circulating cells
      in neoplastic cockles) was conducted. Prevalences ranged from 2.2% (June) to
      13.6% (May), and disease intensity ranged from 18.7% (June) to 95.5% (September).
      These percentages were not correlated with seawater temperature, but rather
      showed unexplained oscillations over the year. Prevalence and intensity of DN
      were higher in cockles found at the surface of sediment compared to those buried
      normally (11.8% vs. 6.7% and 53.0% vs. 40.6%, respectively, p<0.05). DN could
      thus be one mechanism leading to unexplained presence of cockles at the surface
      of the sediment in Arcachon Bay. Ploidy characteristics of neoplastic cells were
      also investigated using FCM, revealing an unusual, broad continuum of ploidy
      distribution from 1.6 to 9.6n. Ploidy values were not in whole numbers in
      contrast to the rounded values reported in other studies. Ploidy varied according
      to DN intensity, with the ploidy distribution of neoplastic cells from lightly
      diseased cockles being unimodal (3.7n median). In contrast, highly-diseased
      cockles showed a bimodal ploidy distribution (3.0n and 4.7n medians). This
      suggests that, in cockles from Arcachon Bay, mechanisms leading to aneuploidy are
      complex, developing during disease progression.

PMID- 20159022
TI  - In vivo characterization of the opioid antagonist nalmefene in mice.
AB  - AIMS: The current study assessed the in vivo antagonist properties of nalmefene
      using procedures previously used to characterize the opioid antagonists naloxone,
      naltrexone, 6beta-naltrexol and nalbuphine. MAIN METHODS: ICR mice were used to
      generate antagonist dose-response curves with intraperitoneal (i.p.) nalmefene
      against fixed A(90) doses of morphine in models of morphine-stimulated
      hyperlocomotion and antinociception. Additional dose-response curves for
      antagonist precipitated opioid withdrawal were run in mice treated acutely
      (100mg/kg, s.c., -4h) or chronically (75mg pellet, s.c., -72h) with morphine.
      Comparisons were made between antagonist potency and degree of precipitated
      withdrawal. KEY FINDINGS: Nalmefene produced dose- and time-related antagonism of
      morphine-induced increases in locomotor activity with a calculated ID(50) (and
      95% confidence interval) of 0.014 (0.007-0.027)mg/kg. Nalmefene produced rapid
      reversal of morphine-induced locomotor activity (5.1min for 50% reduction in
      morphine effect). A 0.32mg/kg dose of nalmefene produced blockade of morphine
      induced antinociception in the 55 degrees C tail-flick test that lasted
      approximately 2h. Nalmefene was able to potently precipitate withdrawal in mice
      treated acutely or chronically with morphine. SIGNIFICANCE: These results
      demonstrate that nalmefene is similar to naloxone and naltrexone with respect to
      its in vivo pharmacology in mice. Specifically, nalmefene produces potent
      antagonism of morphine agonist effects while precipitating severe withdrawal. The
      compound has a slower onset and longer duration of action compared to naloxone
      and naltrexone. The data allows for a more complete preclinical comparison of
      nalmefene against other opioid antagonists including the putative opioid neutral
      antagonist 6beta-naltrexol.

PMID- 20159023
TI  - ABCG2: a potential marker of stem cells and novel target in stem cell and cancer
      therapy.
AB  - ABCG2 is a member of the ATP binding cassette (ABC) transporters, which can pump
      a wide variety of endogenous and exogenous compounds out of cells. Widely
      expressed in stem cells, ABCG2 is also found to confer the side population
      phenotype and is recognized as a universal marker of stem cells. Although the
      precise physiological role of ABCG2 in stem cells is still unclear, existing data
      strongly suggest that ABCG2 plays an important role in promoting stem cell
      proliferation and the maintenance of the stem cell phenotype. In addition, ABCG2
      is also found to be expressed in a number of cancer cells and appears to be a
      marker of cancer stem cells. Moreover, ABCG2 expression in tumors may contribute
      to their formation and progression. Thus, ABCG2 has potential applications in
      stem cell and tumor therapy.

PMID- 20159024
TI  - Feeding rats a high fat/carbohydrate ratio diet reduces jejunal S/I activity
      ratio and unsialylated galactose on glycosylated chain of S-I complex.
AB  - AIMS: We examined whether decreasing jejunal sucrase/isomaltase (S/I) activity
      ratio by feeding rats a high fat/carbohydrate ratio diet is regulated by changing
      glycosylated chains on the S-I complex. MAIN METHODS: Jejunal activities of
      sucrase, isomaltase and beta-1,4-galactosyltransferase were examined in rats fed
      a high fat/carbohydrate or a low fat/carbohydrate ratio diet. The amount of
      galactose and mannose in the glycosylated chain on the S-I complex in rats fed
      both diets was determined using RCA(120) and Con A lectins, respectively. The
      effects of reducing unsialylated galactose from the glycosylated chain on the S-I
      complex were assessed by determining sucrase activity in purified S-I complex
      treated with beta-galactosidase. KEY FINDINGS AND SIGNIFICANCE: Feeding rats a
      high fat/carbohydrate ratio diet reduced jejunal S/I activity ratio in mucosal
      homogenates and purified fractions. The level of unsialylated galactose in
      glycosylated chains on the S-I complex was reduced by feeding rats a high
      fat/carbohydrate ratio diet. The form with reduced levels of unsialylated
      galactose had lower sucrase activity than that with more unsialylated galactose.
      The reduction of galactose on the S-I complex by beta-galactosidase in vitro
      reduced sucrase activity. Feeding rats a high fat/carbohydrate ratio diet also
      reduced jejunal beta-1,4-galactosyltransferase activity. Taken together,
      decreasing the S/I activity ratio by feeding rats a high fat/carbohydrate diet is
      associated with the reduction of unsialylated galactose on the glycosylated chain
      of the S-I complex.

PMID- 20159025
TI  - Overexpression of a 60-kDa heat shock protein enhances cytoprotective function of
      small intestinal epithelial cells.
AB  - AIMS: With the advancement of small intestinal (double balloon and capsule)
      endoscopy technology, incidence of small intestinal lesion caused by nonsteroidal
      anti-inflammatory drugs (NSAIDs) has been known to be high. However, therapy for
      small intestinal mucosal lesion has not yet been developed. Previous studies have
      shown that heat shock proteins (HSPs) are involved in cytoprotection mediated by
      their function as a molecular chaperone. In this study, we examined the effect of
      HSP60 or HSP70 overexpression on hydrogen peroxide-induced (H2O2) or indomethacin
      induced cell damage in the small intestinal epithelial cells. MAIN METHODS: cDNA
      of human HSP60 or HSP70 was transfected to rat small intestinal (IEC-6) cells,
      and HSP60- or HSP70-overexpressing cells were cloned. IEC-6 cells transfected
      with vector only were used as control cells. These cells were treated with H2O2
      (0-0.14mM) or indomethacin (0-2.5mM). The cell viability was determined by MTT
      assay. Cell necrosis was evaluated by LDH-release assay. Further, apoptosis was
      evaluated by caspases-3/7 activity and TUNEL assay. KEY FINDINGS: Cell viability
      after H2O2 or indomethacin treatment was significantly higher in HSP60
      overexpressing cells compared with that in control cells and HSP60-overexpressing
      cells. Apoptotic cells were also reduced in HSP60-overexpressing. CONCLUSION:
      These results indicate that HSP60 plays an important role in protecting small
      intestinal mucosal cells from H2O2-induced or indomethacin-induced cell injury.
      HSP70-overexpressing cells did not show anti-apoptotic ability. SIGNIFICANCE:
      These findings possibly suggest that function of each HSP is different in the
      small intestine. Therefore, for the therapy of small intestinal mucosal lesion,
      HSP60-induction therapy could be a new therapeutic strategy.

PMID- 20159026
TI  - Early experience alters limbic forebrain Fos responses to a stressful
      interoceptive stimulus in young adult rats.
AB  - The present study examined whether manipulation of the early life experience of
      rat pups might alter the later ability of an interoceptive challenge to recruit
      central neural circuits that receive visceral sensory signals and generate stress
      responses. For this purpose, litters were exposed to daily maternal separation
      for either 15min (MS-15) or 180min (MS-180) from postnatal days (P)1 to P10. Pups
      in control litters were raised under standard conditions (i.e., no separations).
      Similar to previous reports in adult rats, adolescent rats (P35-45) with a
      developmental history of MS-15 displayed less anxiety-like behavior on the
      elevated plus maze compared to control and MS-180 rats. As young adults (P50-60),
      rats were anesthetized and perfused with fixative 90min after viscerosensory
      stimulation via lithium chloride (LiCl, 0.15M, 1% BW, i.p.) or saline control. In
      all three rearing groups, Fos activation within brainstem and forebrain regions
      of interest was significantly enhanced after LiCl vs. saline. MS-15 rats tended
      to display fewer LiCl-activated neurons in most brain regions compared with rats
      in the other two rearing groups. This trend reached significance within the
      dorsal bed nucleus of the stria terminalis. The ability of MS-15 to alter limbic
      forebrain activation in rats after an interoceptive challenge may contribute to
      the effect of early life experience to modulate physiological and behavioral
      stress responses more generally.

PMID- 20159027
TI  - Conditioned ejaculatory preference in male rats paired with haloperidol-treated
      females.
AB  - We have shown that males trained to copulate with the same almond-scented female
      in environments that restrict access to the female during copulation develop a
      conditioned ejaculation preference (CEP) for their familiar female over a novel
      one. These findings suggest that copulation in environments in which the female
      spends more time away from the male and in which the male anticipates female
      copulatory contact facilitates the development of CEP. However, conditioned place
      and partner preference studies have shown that males prefer easy over obstructed
      access to the female partners during copulation. The objective of this study was
      to attempt to understand the discrepancy between the findings by examining the
      importance of female proceptive behavior and genital stimulation in the
      development of CEP while keeping the environment constant. Experiment 1
      investigated the effect of administering a range of doses of haloperidol, a
      dopamine D2-receptor antagonist, to females, on female and male sexual behavior.
      Haloperidol treatment significantly reduced female proceptive behaviors in a dose
      dependent manner. Experiment 2 examined the importance of female proceptive
      behaviors in the development of CEP by inhibiting those behaviors with
      haloperidol. Following alternating copulatory trials with scented or unscented
      haloperidol- or saline-treated females, males were given a partner preference
      test. Males displayed a preference to copulate with females bearing cues
      predictive of prior copulation with haloperidol-treated females, suggesting that
      males do not require female proceptive behaviors for the development of CEP. We
      conclude that copulation to ejaculation at a male's preferred rate is essential
      for the development of CEP, as it is for the development of a sexually
      conditioned place preference.

PMID- 20159028
TI  - Alterations in fear response and spatial memory in pre- and post-natal zinc
      supplemented rats: remediation by copper.
AB  - The role of zinc in the nervous system is receiving increased attention. At a
      time when dietary fortification and supplementation have increased the amount of
      zinc being consumed, little work has been done on the effects of enhanced zinc on
      behavior. Both zinc and copper are essential trace minerals that are acquired
      from the diet; under normal conditions the body protects against zinc overload,
      but at excessive dosages, copper deficiency has been seen. In order to examine
      the effect of enhanced metal administration on learning and memory, Sprague
      Dawley rats were given water supplemented with 10ppm Zn, 10ppm Zn+0.25ppm Cu, or
      normal lab water, during pre- and post-natal development. Fear conditioning tests
      at 4months showed significantly higher freezing rates during contextual retention
      and extinction and cued extinction for rats drinking water supplemented with
      zinc, suggesting increased anxiety compared to controls raised on lab water.
      During the MWM task at 9months, zinc-enhanced rats had significantly longer
      latencies to reach the platform compared to controls. The addition of copper to
      the zinc supplemented water brought freezing and latency levels closer to that of
      controls. These data demonstrate the importance of maintaining appropriate intake
      of both metals simultaneously, and show that long-term supplementation with zinc
      may cause alterations in memory.

PMID- 20159029
TI  - Serum total cholesterol correlates positively to central serotonergic turnover in
      male but not in female subjects.
AB  - Reduced central serotonergic activity and low total serum cholesterol have been
      related to increased aggression, violent behavior, and suicidality. Searching for
      a correlation between them, we estimated serum total cholesterol and CSF levels
      of the main serotonin metabolite 5-HIAA in medication free male and female
      subjects for whom diagnostic lumbar puncture was performed. To eliminate age
      influence, we included in the study subjects in the age range 26 to 45years. In a
      group of 62 subjects (30 males), found negative after diagnostic neurological
      examination, the correlation was not significant for the whole group, but after
      sex stratification, a significant positive correlation was revealed for males but
      not for females. These results were replicated in a second group of 76 subjects
      (31 males) with clinical and laboratory findings suggestive of multiple sclerosis
      (clinically isolated syndrome). The results link low cholesterol to low
      serotonergic activity only in males, predisposing them for violent and risky
      behaviors. This phenomenon could be seen as an evolutionary trait, possibly a
      result of the distinct role of males in a hunter-gatherer environment of
      evolutionary adaptedness, and may contribute to the understanding of the higher
      incidence of violent behavior observed in males.

PMID- 20159030
TI  - Prostaglandin E synthases: Understanding their pathophysiological roles through
      mouse genetic models.
AB  - Prostaglandin E synthase (PGES), which converts cyclooxygenase (COX)-derived
      prostaglandin H(2) (PGH(2)) to PGE(2), is known to comprise a group of at least
      three structurally and biologically distinct enzymes. Two of them are membrane
      bound and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear
      protein that is markedly induced by proinflammatory stimuli and downregulated by
      anti-inflammatory glucocorticoids as in the case of COX-2. It is functionally
      coupled with COX-2 in marked preference to COX-1. mPGES-2 is synthesized as a
      Golgi membrane-associated protein, and the proteolytic removal of the N-terminal
      hydrophobic domain leads to the formation of a mature cytosolic enzyme. This
      enzyme is rather constitutively expressed in various cells and tissues and is
      functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is
      constitutively expressed in a wide variety of cells and is functionally linked to
      COX-1 to promote immediate PGE(2) production. Recently, mice have been engineered
      with specific deletions in each of these three PGES enzymes. In this review, we
      summarize the current understanding of the in vivo roles of PGES enzymes by
      knockout mouse studies and provide an overview of their biochemical properties.

PMID- 20159032
TI  - STAT1 and pathogens, not a friendly relationship.
AB  - STAT1 belongs to the STAT family of transcription factors, which comprises seven
      factors: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B and STAT6. STAT1 is a 91 kDa
      protein originally identified as the mediator of the cellular response to
      interferon (IFN) alpha, and thereafter found to be a major component of the
      cellular response to IFNgamma. STAT1 is, in fact, involved in the response to
      several cytokines and to growth factors. It is activated by cytokine receptors
      via kinases of the JAK family. STAT1 becomes phosphorylated and forms a dimer
      which enters the nucleus and triggers the transcription of its targets. Although
      not lethal at birth, selective gene deletion of STAT1 in mice leads to rapid
      death from severe infections, demonstrating its major role in the response to
      pathogens. Similarly, in humans who do not express STAT1, there is a lack of
      resistance to pathogens leading to premature death. This indicates a key, non
      redundant function of STAT1 in the defence against pathogens. Thus, to
      successfully infect organisms, bacterial, viral or parasitic pathogens must
      overcome the activity of STAT1, and almost all the steps of this pathway can be
      blocked or inhibited by proteins produced in infected cells. Interestingly, some
      pathogens, like the oncogenic Epstein-Barr virus, have evolved a strategy which
      uses STAT1 activation.

PMID- 20159031
TI  - mPGES-1 as a target for cancer suppression: A comprehensive invited review
      "Phospholipase A2 and lipid mediators".
AB  - Prostaglandin E(2) (PGE(2)) is a bioactive lipid that can elicit a wide range of
      biological effects associated with inflammation and cancer. The physiological
      roles of PGE(2) are diverse, mediated in part through activation of key
      downstream signaling cascades via transmembrane EP receptors located on the cell
      surface. Elevated levels of COX-2 and concomitant overproduction of PGE(2) are
      often found in human cancers. These observations have led to the use of non
      steroidal anti-inflammatory drugs (NSAIDs) as chemopreventive agents,
      particularly for colorectal cancer (CRC). Their long-term use, however, may be
      associated with gastrointestinal toxicity and increased risk of adverse
      cardiovascular events, prompting the development of other enzymatic targets in
      this pathway. This review will focus on recent efforts to target the terminal
      synthase, mPGES-1, for cancer chemoprevention. The role of mPGES-1 in the
      pathogenesis of various cancers is discussed. In addition, an overview of recent
      efforts to develop small molecule inhibitors that target the protein with high
      selectivity is also be reviewed.

PMID- 20159033
TI  - Ageing alters the supramolecular architecture of OxPhos complexes in rat brain
      cortex.
AB  - Activity and stability of life-supporting proteins are determined not only by
      their abundance and by post-translational modifications, but also by specific
      protein-protein interactions. This holds true both for signal-transduction and
      energy-converting cascades. For vital processes such as life-span control and
      senescence, to date predominantly age-dependent alterations in abundance and to
      lesser extent in post-translational modifications of proteins are examined to
      elucidate the cause of ageing at the molecular level. In mitochondria of rat
      cortex, we quantified profound changes in the proportion of supramolecular
      assemblies (supercomplexes) of the respiratory chain complexes I, III(2), IV as
      well as of the MF(o)F(1) ATP synthase (complex V) by 2D-native/SDS
      electrophoresis and fluorescent staining. Complex I was present solely in
      supercomplexes and those lacking complex IV were least stable in aged animals
      (2.4-fold decline). The ATP synthase was confirmed as a prominent target of age
      associated degradation by an overall decline in abundance of 1.5-fold for the
      monomer and an 2.8-fold increase of unbound F(1). Oligomerisation of the ATP
      synthase increases during ageing and might modulate the cristae architecture.
      These data could explain the link between ageing and respiratory control as well
      as ROS generation.

PMID- 20159034
TI  - Cytotoxicity and apoptosis induction on RTG-2 cells of 2,2',4,4'
      tetrabromodiphenyl ether (BDE-47) and decabrominated diphenyl ether (BDE-209).
AB  - Recently, the environmental residues of polybrominated diphenyl ethers (PBDEs)
      have markedly increased. In particular, the levels of certain PBDE congeners in
      fish have raised concern regarding potential risks associated with dietary PBDEs
      exposures. However, little is known regarding PBDE-mediated cell injury in
      relevant in vitro fish cell models. In this study, the cytotoxic effects of
      2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and decabrominated diphenyl ether
      (BDE-209) on RTG-2 cells were investigated. RTG-2 cells were incubated with
      different concentrations of BDE-47 and BDE-209 (1-100 microM) for 72 h, and a set
      of bioassays were conducted to measure: cell viability (evaluated by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and neutral
      red (NR) uptake), lactate dehydrogenase (LDH) leakage, reactive oxygen species
      (ROS) formation and cell apoptosis. The results showed that BDE-47 and BDE-209
      inhibited the cells viability, increased LDH leakage, and induced cell apoptosis
      in time and concentration-dependent manner. All significant effects were observed
      at concentrations of 12.5 microM and above for BDE-47 and 25 microM and above for
      BDE-209 (P<0.05). At the concentration of 100 microM BDE-47 and BDE-209, the cell
      viability of the exposed cells dropped to about 40% and 50% of the control, and
      the apoptotic rates were 52.6% and 34.6%, respectively. After 12h exposure, a
      concentration-dependent increases of BDE-47 and BDE-209 (12.5-100 microM) in ROS
      formation were observed. Collectively, the results of cell viability, LDH
      leakage, cell apoptosis and ROS formation demonstrated that the toxic mechanism
      of PBDEs on RTG-2 might be mediated by oxidative stress.

PMID- 20159035
TI  - Propyl gallate inhibits the growth of calf pulmonary arterial endothelial cells
      via glutathione depletion.
AB  - Propyl gallate (PG) as a synthetic antioxidant exerts a variety of effects on
      tissue and cell functions. Here, we evaluated the effects of PG on the growth and
      death of endothelial cells (ECs), especially calf pulmonary artery endothelial
      cells (CPAEC) in relation to reactive oxygen species (ROS) and glutathione (GSH).
      PG dose-dependently inhibited the growth of CPAEC and human umbilical vein
      endothelial cells (HUVEC) at 24h. PG induced cell death in CPAEC, which was
      accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)).
      PG generally increased ROS level in CPAEC but not in HUVEC. PG also dose
      dependently increased GSH depleted cells in both ECs. The treatment with
      antioxidant of N-acetyl-cysteine (NAC) or ascorbate acid (AA) prevented CPAEC
      growth inhibition and death by PG, which was accompanied by the attenuation of
      GSH depletion but not by the reduction of ROS level. In conclusion, PG induced
      growth inhibition and death of ECs, especially CPAEC via GSH depletion.

PMID- 20159036
TI  - Involvement of the MEKK1 signaling pathway in the regulation of epicardial cell
      behavior by hyaluronan.
AB  - During embryonic development, cells comprising the outermost layer of the heart
      or epicardium play a critical role in the formation of the coronary vasculature.
      Thus, uncovering the molecular mechanisms that govern epicardial cell behavior is
      imperative to better understand the etiology of cardiovascular diseases. In this
      study, we investigated the function of hyaluronan (HA), a major component of the
      extracellular matrix, in the modulation of epicardial signaling. We show that
      stimulation of epicardial cells with high molecular weight HA (HMW-HA) promotes
      the association of MEKK1 with the HA receptor CD44 and induces MEKK1
      phosphorylation. This leads to the activation of two distinct pathways, one ERK
      dependent and another NFkappaB-dependent. Furthermore, HMW-HA stimulates
      epicardial cells to differentiate and invade, as suggested by increased vimentin
      expression and enhanced invasion through a collagen matrix. Blockade of CD44,
      transfection with a kinase-inactive MEKK1 construct or the use of ERK1/2 and
      NFkappaB inhibitors significantly abrogates the invasive response to HMW-HA.
      Together, these findings suggest an important role for HA in the regulation of
      epicardial cell fate via activation of MEKK1 signaling cascades.

PMID- 20159037
TI  - In vivo evaluation of two new sustained release formulations elaborated by one
      step melt granulation: level A in vitro-in vivo correlation.
AB  - The objective of this study was to evaluate in vivo two sustained release
      formulations elaborated by a one-step melt granulation method using theophylline
      as model drug. Both formulations presented differences in the in vitro release
      profile due to the hydrophilic or lipophilic nature of the binder employed (PEG
      6000 or glycerol monostearate). The formulations were administered to Beagle
      dogs, and plasma levels were compared. Both formulations provided a sustained
      plasma concentration profile after oral administration to dogs. Significant
      differences (p<0.05) in the plasma concentration-time curves between the two
      formulations were found, with higher C(max) (6.05+/-2.00 vs. 2.55+/-0.82
      microg/mL), higher AUC(0-infinity) (70.24+/-16.10 vs. 33.00+/-8.96 h microg/mL)
      and delayed T(max) (6.00+/-2.12 vs. 3.17+/-0.98 h) for the formulation containing
      PEG 6000. Absolute bioavailability of theophylline was 96% and 46% for the
      formulations containing PEG 6000 and glycerol monostearate, respectively. These
      results are consistent with those obtained in vitro, with slower release rate of
      theophylline from tablets elaborated with glycerol monostearate than that
      obtained with tablets elaborated with PEG 6000. Moreover, the formulation
      containing PEG 6000 provided a plasma concentration-time profile similar to that
      obtained with the marketed formulation Theo-Dur. A very good Level A IVIVC was
      observed between dissolution and absorption profiles of the drug from both test
      formulations. Our results showed that one-step melt granulation in a high shear
      mixer allows for an easy modulation of the release profile and, consequently, of
      the plasma level profile of the drug by selecting the type of binder used.

PMID- 20159038
TI  - Pl-nectin, a discoidin family member, is a ligand for betaC integrins in the sea
      urchin embryo.
AB  - Pl-nectin is a component of the extracellular matrix that surrounds embryos of
      the sea urchin Paracentrotus lividus. Pl-nectin mediates adhesion of dissociated
      embryonic cells to substrates and interfering with ectodermic cells contacting Pl
      nectin results in defects in skeleton growth and morphogenesis. Recently, we
      reported that Pl-nectin is a new member of the discoidin family, in agreement
      with the notion that many discoidin-containing proteins are involved in cell
      adhesion processes as integrin ligands. To better understand the molecular basis
      for the interaction of Pl-nectin with ectoderm, we investigated the hypothesis
      that Pl-nectin is an integrin ligand in sea urchin embryos. We show that in P.
      lividus embryos, betaC-containing integrins localize to the apical surface of
      ectodermic cells, which are in contact with Pl-nectin. Immunoprecipitation
      experiments indicate that the two proteins are part of a complex in vivo and
      affinity chromatography indicates that betaC-containing integrin receptors bind
      purified Pl-nectin. These data support a model in which ectodermic integrins
      binding to Pl-nectin mediate cellular adhesion to the hyaline layer. Regulated
      adhesion of cells to the hyaline layer is a critical component of several
      morphogenetic processes and the identification of the receptors and ligands
      involved provides new opportunities to investigate the underlying molecular
      mechanisms of ECM adhesion and morphogenesis.

PMID- 20159040
TI  - Focal adhesion kinase functions downstream of Sema3A signaling during axonal
      remodeling.
AB  - Axon refinement is a necessary event for sculpting the final wiring of neural
      circuits. Although some factors have been identified that cause axonal arbor
      remodeling, the molecular pathways transducing these extracellular signals to
      adhesion disassembly and the cytoskeleton are poorly understood. Here we show
      that conditional ablation of Focal adhesion kinase (Fak) abolishes axon
      remodeling induced by Semaphorin-3A (Sema3A) in hippocampal neurons. Sema3A
      elicits divergent effects on different tyrosine residues of FAK: it increases
      phosphorylation of Tyr397, the kinase domain and the tyrosine residue 925, and
      decreases phosphorylation of Tyr407 and Tyr861. Moreover, Sema3A mediates
      mechanisms that contribute to the disassembly of adhesion contacts in a FAK
      dependent manner: tyrosine phosphorylation of alpha-actinin and FAKY925 that
      decreases FAK-Paxillin interaction. Altogether, our results provide novel
      insights into the spatiotemporal dynamics of FAK activation mediated by Sema3A
      and on its interaction with its downstream effectors: Paxillin and alpha-actinin
      in neurons.

PMID- 20159039
TI  - High content screening of cortical neurons identifies novel regulators of axon
      growth.
AB  - Neurons in the central nervous system lose their intrinsic capacity for axon
      regeneration as they mature, and it is widely hypothesized that changes in gene
      expression are responsible. Testing this hypothesis and identifying the relevant
      genes has been challenging because hundreds to thousands of genes are
      developmentally regulated in CNS neurons, but only a small subset are likely
      relevant to axon growth. Here we used automated high content analysis (HCA)
      methods to functionally test 743 plasmids encoding developmentally regulated
      genes in neurite outgrowth assays using postnatal cortical neurons. We identified
      both growth inhibitors (Ephexin, Aldolase A, Solute Carrier 2A3, and Chimerin),
      and growth enhancers (Doublecortin, Doublecortin-like, Kruppel-like Factor 6, and
      CaM-Kinase II gamma), some of which regulate established growth mechanisms like
      microtubule dynamics and small GTPase signaling. Interestingly, with only one
      exception the growth-suppressing genes were developmentally upregulated, and the
      growth-enhancing genes downregulated. These data provide important support for
      the hypothesis that developmental changes in gene expression control neurite
      outgrowth, and identify potential new gene targets to promote neurite outgrowth.

PMID- 20159041
TI  - Extraction and purification of human interleukin-10 from transgenic rice seeds.
AB  - Recombinant protein production system using transgenic rice grain offers many
      advantages in higher accumulation, preservation, lower production cost, ease of
      scale up and low risk of contamination by toxic materials. We developed a
      transgenic rice strain whose seeds accumulate human interleukin (IL)-10, a
      cytokine that suppresses inflammation-related immune responses. We also developed
      a method of extracting and purifying IL-10 from rice seeds. A biochemical
      crosslinking method was used to detect the biologically active noncovalent dimer
      of IL-10. This method was useful for developing efficient methods of refolding
      and purification. The purified IL-10 comprised only noncovalent dimers and showed
      higher activity than the commercial IL-10. The purified IL-10 had very low
      endotoxin contamination and is expected to have broad clinical application.

PMID- 20159042
TI  - Strategies to maximize expression of rightly processed human interferon alpha2b
      in Pichia pastoris.
AB  - The human interferon alpha 2b (IFN alpha2b) belongs to the interferon family of
      cytokines that exerts many biological functions like inhibition of virus
      multiplication, repression of tumour growth and other immunological functions.
      Herein, a synthetic gene coding for human IFN alpha2b was cloned and integrated
      into a methylotropic yeast-Pichiapastoris. The recombinant human IFN alpha2b
      protein (approximately 19kDa) could be successfully expressed in Pichiapastoris
      to a level of nearly 300mg/L with nearly 93% recovery on purification using a
      single anion exchange chromatography step. A novel media component dimethyl
      sulphoxide (DMSO) was found to aid in expression of rightly processed IFN alpha2b
      form with dramatic reduction in the expression of a 20kDa IFN isoform contaminant
      frequently observed by other workers. The identity of the 20kDa isoform was
      confirmed by N terminal sequencing which showed extra eleven amino acids at the N
      terminal portion of the IFN molecule obtained due to incorrect processing by the
      host KEX2 protease. The purified IFN alpha2b (19kDa) preparation was confirmed by
      N terminal sequencing, and characterized by MALDI-TOF and Agilent 2100
      Bioanalyzer. The bioassay of the recombinant protein gave a specific activity of
      >2x10(8)IU/mg.

PMID- 20159043
TI  - A systematic approach to isolate mono-disperse membrane proteins - purification
      of zinc transporter ZntB.
AB  - Obtaining mono-disperse and stable protein is a requirement for successful
      structural and biochemical investigation of proteins. For membrane proteins, such
      preparation is one of the major hurdles, which consequently has contributed to
      the slow progress in studying them. During the past few years, many screening
      methods have been developed to make studies of membrane proteins more efficient.
      Despite these advances, many membrane proteins remain challenging to even isolate
      in a stable and homogeneous form. The bacterial zinc transporter ZntB is such a
      protein, for which no isolation procedure has been reported. Here, we present a
      systematic approach to obtain homogeneous and mono-disperse zinc transporter ZntB
      in quantities sufficient for structural and biochemical studies. Important
      aspects of this study that can be applied to other membrane proteins are also
      discussed.

PMID- 20159044
TI  - Phylogeny, divergence-time estimation, biogeography and social parasite-host
      relationships of the Holarctic ant genus Myrmica (Hymenoptera: Formicidae).
AB  - We reconstructed a molecular phylogeny of the ant genus Myrmica, tested
      reciprocal monophyly of the Nearctic and Palearctic representatives, and inferred
      social parasite-host relationships for five workerless inquilines and four
      temporary parasites. We sequenced six gene fragments of 106 specimens (17 not
      identified to species), analysed the data with Bayesian phylogenetic inference
      and maximum likelihood, and estimated divergence times using penalized
      likelihood. Our well resolved phylogeny supported most morphologically defined
      species groups. The Nearctic and Palearctic species were not reciprocally
      monophyletic, which suggested repeated species interchange across the Beringian
      land bridge. Parasitism evolved several times in Myrmica. Three inquilines and
      one temporary parasite were closest relatives of their host, two inquiline
      species and one temporary parasite clustered basally to their host(s), and two
      temporary parasites more distantly. Myrmica probably diversified following
      drastic climatic cooling at the Eocene-Oligocene boundary ca. 34 Ma, the oldest
      species groups being rugosa and ritae in central and southeastern Asia. The
      oldest inquiline, Myrmica karavajevi, was estimated at 17 Ma, the youngest
      species M. hirsuta at 0.8 Ma, whereas the microgyne of M.rubra is an
      intraspecific inquiline.

PMID- 20159045
TI  - Prospective randomized comparison between the conventional electroanatomical
      system and three-dimensional rotational angiography during catheter ablation for
      atrial fibrillation.
AB  - BACKGROUND: Theoretically, the use of electroanatomical mapping systems may
      reduce radiation exposure, while three-dimensional rotational atriography (3DATG)
      may increase exposure. Anatomical representation and image registration using
      3DATG are likely to be superior, but the net clinical benefit of either system is
      unknown. OBJECTIVE: The purpose of this prospective randomized two-center study
      was to compare the procedural and clinical outcome of patients with atrial
      fibrillation (AF) treated by catheter ablation using either three-dimensional
      (3D) electroanatomical mapping (Carto) or 3DATG. METHODS: From November 2007 to
      November 2008, 91 consecutive patients with AF (mean age 58 +/- 10 years; 63%
      paroxysmal AF, 37% persistent AF) from two centers (Bordeaux and Boston) were
      randomized to ablation using either 3DATG (44 patients) or Carto (47 patients).
      RESULTS: Of the 47 left atrial shells acquired with 3DATG, one was
      uninterpretable. There was no difference in total radiofrequency applications (72
      +/- 23 vs. 79 +/- 33 minutes, respectively, P = .296), procedural duration (232
      +/- 65 vs. 218 +/- 67 minutes; P = .335), fluroroscopic duration (75 +/- 28 vs.
      67 +/- 26 minutes; P = .151), or radiation exposure (71,810 +/- 42,954 vs. 68,009
      +/- 38,345 mGy cm(2); P = .719) between procedures performed with 3DATG or Carto.
      After a mean follow-up of 10 +/- 4 months, there was no difference in clinical
      outcome using either Carto or 3DATG concerning total arrhythmia recurrence (34%
      versus 38%; P = .668) or AF recurrence (20% vs. 15%; P = .555). CONCLUSION: Three
      dimensional ATG-guided AF ablation has similar radiation exposure and procedural
      and outcome characteristics compared with Carto-guided ablation. The ease of use
      and accurate 3D representation of the left atrium make 3DATG a reasonable
      alternative to conventional 3D electroanatomical mapping systems, however,
      without advanced mapping functions.

PMID- 20159046
TI  - Sinus rhythm is associated with fewer heart failure symptoms: insights from the
      AFFIRM trial.
AB  - BACKGROUND: The AFFIRM trial demonstrated no mortality benefit from a rhythm
      control strategy compared with rate control of atrial fibrillation (AF). However,
      AF is associated with greater morbidity and mortality and poorer functional
      status than sinus rhythm, which is more likely to be achieved with a rhythm
      control strategy. OBJECTIVE: This study sought to compare heart failure (HF)
      symptoms in the different AFFIRM (Atrial Fibrillation Follow-Up Investigation of
      Rhythm Management) subgroups depending on the prevalence of AF or sinus rhythm
      throughout the follow-up period. METHODS: This study analyzed a limited-access
      dataset from the AFFIRM trial, provided by the National Heart, Lung, and Blood
      Institute. RESULTS: Symptomatic HF was more common in the rate control than in
      the rhythm control arm. On analysis based on actual rhythm, New York Heart
      Association functional status was the best in patients who were in stable sinus
      rhythm, worse if they were consistently in AF, and much worse if they were
      changed back and forth between the rhythm control and rate control strategies.
      Patients in all groups had fewer HF symptoms and required less HF medications
      when they were in sinus rhythm compared with AF, except for those who crossed
      over from the rhythm to the rate control strategy. CONCLUSION: Patients in the
      rhythm control arm had fewer HF symptoms than those in the rate control arm.
      Stable sinus rhythm was associated with the best functional status. Patients who
      are the most symptomatic in AF but are unable to maintain normal sinus rhythm if
      treated by the means used in the AFFIRM trial may be candidates for other
      treatment options, such as ablation.

PMID- 20159047
TI  - Defining conditions for the co-culture of Caco-2 and HT29-MTX cells using Taguchi
      design.
AB  - INTRODUCTION: The co-culture of Caco-2 and HT29 cells for testing intestinal drug
      and nutrient transport and metabolism provides the presence of both absorptive
      and goblet cells, both of which have different culture requirements for optimal
      growth and function. The research on the co-culture of Caco-2 and HT29 cells is
      very limited in respect to refining specific conditions that reduce intra- and
      inter-laboratory variations. In the present study we reported conditions that
      enable reproducible results to be obtained for drug permeability using in vitro
      co-culture of Caco-2 and HT29-MTX based on Taguchi experimental design. METHODS:
      The selection of four factors that specified cell culture conditions, namely
      culture medium, seeding time, seeding density, and Caco-2:HT29-MTX ratio on TEER
      value and individual permeability coefficients of propranolol, ketoprofen and
      furosemide was established. Based on the selected conditions for co-culture, we
      also confirmed the functionality of the final chosen culture condition using
      nitric oxide as an indicator of intestinal inflammation. RESULTS: Choice of cell
      culture time and culture medium represented two of the most important factors
      that affected TEER values and the permeability coefficients of the model drugs.
      On the other hand, the seeding density and the Caco-2:HT29-MTX ratio exerted no
      significant influence on TEER values and the drug permeability coefficients. No
      absolute optimal cell culture condition could be obtained for all drugs; however
      subsequent confirmation experiments concluded that excellent precision for TEER
      values and drug permeability coefficients was obtained from the two operators
      using the following combination of conditions, namely an initial seeding density
      of 1 x 10(5) Caco-2 and HT29-MTX cells/cm(2) at a ratio of 9:1, followed by a
      21day culture time in MEM medium. Finally, functionality of the co-culture model
      system using the above selected in vitro conditions resulted in comparable nitric
      oxide synthesis to that of a Caco-2 cell monolayer. DISCUSSION: Taguchi
      experimental design enabled us to define a combination of in vitro culture
      conditions that resulted in excellent operator reproducibility for determining
      drug permeability coefficients in a Caco-2 and HT29-MTX co-culture system.
      Moreover, the selected conditions used in co-culture of absorptive and goblet
      intestinal cells did not compromise the synthesis of nitric oxide, an indicator
      of inflammation, measured in Caco-2 monolayers.

PMID- 20159048
TI  - First isolation of Desulfovibrio from the human vaginal flora.
AB  - Four Desulfovibrio species, including 2 subtypes of 1 species, namely,
      Desulfovibrio piger, Desulfovibrio desulfuricans MB subtype and Essex 6 subtype,
      Desulfovibrio fairfieldensis, and Desulfovibrio vulgaris, have been isolated from
      the human oral and intestinal flora, but not previously from the vaginal flora.
      They are opportunistic pathogens and have been considered as possible
      environmental and etiologic agents involved in ulcerative colitis and chronic
      periodontitis. We isolated Desulfovibrio intestinalis from vaginal specimens of
      four Japanese women; a species which has not been previously isolated from
      humans. The vaginal isolates were highly resistant to cefoxitin, piperacillin,
      and piperacillin-tazobactam but were susceptible to the other antimicrobial
      agents tested. Our findings suggested that vaginal Desulfovibrio species may be
      involved in gynecological or obstetric pathology, and provides additional
      information of the medical relevance on human Desulfovibrio species.

PMID- 20159049
TI  - Intestinal and immunological effects of daily oral administration of
      Lactobacillus salivarius CECT5713 to healthy adults.
AB  - There is an increasing interest in the intestinal and immunological effects of
      probiotics. The aim of the present study is to evaluate the tolerance and
      beneficial effects in healthy adults of the strain, Lactobacillus salivarius
      CECT5713 isolated from breast milk. A phase II, randomized, double-blinded,
      placebo-controlled human clinical trial was carried out in 40 healthy adults. The
      Probiotic group received a daily dose of 2 x 10(8) CFU of L. salivarius CECT5713
      in capsules during 4 weeks while volunteers of the control received only a
      placebo. Gastrointestinal and immunological parameters were analyzed. Results
      showed that L. salivarius CECT5713 was well tolerated and no adverse effects were
      detected. Consumption of the probiotic strain increased fecal lactobacilli counts
      (7.9+/-0.1 vs. 7.05+/-0.2 CFU/g feces, P=0.001). Also, an improvement in the
      frequency of defecation (P=0.04) was observed. Probiotic treatment induced
      significantly the percentage of NK cells and monocytes, as well as the plasmatic
      levels of immunoglobulins M, A and G, and the regulatory cytokine IL-10 (72.3+/
      11.7 in probiotic group vs. 27.3+/-6.4 pg/mL in control group, P<0.01). Thus, it
      can be concluded that daily administration of L. salivarius CECT5713 to healthy
      adults is safe and improve gut microbiota and different parameters related to
      immune response.

PMID- 20159050
TI  - Detection of resistance genes and susceptibility patterns in Bacteroides and
      Parabacteroides strains.
AB  - Susceptibility to five antimicrobials was determined for Bacteroides spp. (n =
      52) and Parabacteroides distasonis (n = 8). All isolates were susceptible to
      metronidazole. The resistance rates to ampicillin, cefoxitin, tetracycline and
      clindamycin were 98%, 9.6%, 65.3% and 19.2% of the Bacteroides strains,
      respectively. The genes cepA, cfiA, cfxA, tetQ, ermF and nim were found in 69.2%,
      17.3% 9.6%, 50%, 7.7% and 3.8% for these strains respectively. All P. distasonis
      strains were resistant to ampicilin. Cefoxitin, tetracycline and clindamycin
      resistance rates were 75%, 87.5% and 50%, respectively. The ermF and nim genes
      were absent and 37.5%, 12.5%, 12.5% and 87.5% of this strains possessed cepA,
      cfiA, cfxA and tetQ genes, respectively. Ten cfiA gene positive strains of
      Bacteroides and Parabacteroides were submitted to E-test with imipenem and
      amoxicillin-clavulanate. The resistance rate to imipenem was 4.1% and 8.3% to
      amoxicillin-clavulanate. This feature is for the first time described in Brazil.

PMID- 20159051
TI  - Isolation and evaluation of immunological adjuvant activities of saponins from
      the roots of Pulsatilla chinensis with less adverse reactions.
AB  - In this study, the saponins (PCS) from the roots of Pulsatilla chinensis were
      evaluated for its haemolytic activity, acute toxicity and tested for potential
      adjuvant activity in mice immunized with ovalbumin (OVA) compared with that of
      Quil A saponin. The haemolytic activity of PCS was determined using 0.5% rabbit
      red blood cell with values of 15.41 and 7.42% at concentrations of 500 and
      250microg/mL, respectively. The saponins were tested for their toxicity by
      lethality in mice and were found to be less toxic at the same dose than their
      counterpart Quil A. ICR mice were immunized subcutaneously with OVA 100microg in
      phosphate-buffered saline (PBS) alone or with OVA 100microg in the presence of
      Quil A (10microg) or PCS (50, 100 or 200microg) twice at a 2-week interval. Four
      weeks later, the ConA-, LPS-, and OVA-induced splenocyte proliferation, OVA
      specific antibodies levels (IgG, IgG1, and IgG2a) in serum, IL-2, and TNF-alpha
      were significantly enhanced by PCS at a high dose compared to that induced by
      Quil A. The P values of various testing activities in saponin-treated groups were
      obviously differential to that in the OVA-immunized mice (p<0.05 or p<0.01). This
      finding suggested that PCS might have an effect on Th1 and Th2 helper T cells. In
      conclusion, the results indicated that PCS showed slight side effects and at an
      appropriate dose could be used as a vaccine adjuvant to increase immune
      responses.

PMID- 20159052
TI  - Fluorofenidone protects mice from lethal endotoxemia through the inhibition of
      TNF-alpha and IL-1beta release.
AB  - The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which
      stimulates macrophages/monocytes to sequentially release proinflammatory factors
      like TNF-alpha and IL-1beta. Fluorofenidone (AKF-PD) is a novel pyridone agent,
      which exerts a strong antifibrotic effect. In this work, we showed that AKF-PD
      also exert an inhibitory effect on acute systemic inflammatory response. AKF-PD
      treatment significantly increased survival in animals with established
      endotoxemia. In addition, AKF-PD treatment significantly reduced circulating
      levels of TNF-alpha and IL-1beta during endotoxemia. In macrophage cultures, AKF
      PD inhibited the release of TNF-alpha and IL-1beta in a dose-dependent manner. In
      conclusion, these results indicate that AKF-PD inhibits the release of the
      proinflammatory cytokines (TNF-a and IL-1beta) and improves survival during
      lethal endotoxemia, which suggest this new pyridone agent can be a novel
      candidate for therapy of septic shock.

PMID- 20159053
TI  - Prevalence and correlates of handgun access among adolescents seeking care in an
      urban emergency department.
AB  - OBJECTIVE: To determine prevalence and correlates of handgun access among
      adolescents seeking care in an urban Emergency Department (ED) in order to inform
      future injury prevention strategies. METHODS: In this observational cross
      sectional study performed in the ED of a large urban hospital, 14- to 18-year-old
      adolescents completed a computerized survey of risk behaviors. Adolescents
      seeking ED care (for injury or medical complaint) were approached seven days a
      week over a 22-month period. Validated measures included measures of
      demographics, sexual activity, substance use, injury, violent behavior, and
      handgun access. A logistic regression model predicting handgun access was
      performed. RESULTS: A total of 3050 adolescents completed the survey (44% male,
      58.9% African-American), with 417 (12%) refusing to participate. One-third of the
      sample (n=1003) reported access to a handgun, and of those 54% were males
      (n=542). Logistic regression results indicated that older age (AOR: 1.58; 95% CI:
      1.30-1.94), African-American race (AOR: 1.34; 95% CI: 1.11-1.61), male gender
      (AOR: 1.99; 95% CI: 1.66-2.37), and being employed (AOR: 1.35; 95% CI: 1.11
      1.65), as well as seeking ED care for a medical complaint as compared to
      intentional injury (AOR: 1.69; 95% CI 1.62-2.50) predicted handgun access. Binge
      drinking (AOR: 1.75; 95% CI: 1.37-2.27), marijuana use (AOR: 1.93; 95% CI: 1.58
      2.36), sexual activity (AOR: 1.64; 95% CI: 1.32-2.02), prior injury by a gun
      (AOR: 1.80; 95% CI: 1.32-2.46), serious physical violence (AOR: 1.37; 95% CI:
      1.13-1.66) and group fighting (AOR: 2.07; 95% CI: 1.68-2.56) also predicted
      access. CONCLUSIONS: High rates of handgun access were evident among adolescents
      presenting in an inner city ED, including those seeking care for non-injury
      related reasons. Adolescents with access to handguns were more likely to report
      risk behaviors and past injury, providing clinicians with an opportunity for
      injury prevention initiatives.

PMID- 20159054
TI  - The use of narrative text for injury surveillance research: a systematic review.
AB  - OBJECTIVE: To summarise the extent to which narrative text fields in
      administrative health data are used to gather information about the event
      resulting in presentation to a health care provider for treatment of an injury,
      and to highlight best practise approaches to conducting narrative text
      interrogation for injury surveillance purposes. DESIGN: Systematic review. DATA
      SOURCES: Electronic databases searched included CINAHL, Google Scholar, Medline,
      Proquest, PubMed and PubMed Central. Snowballing strategies were employed by
      searching the bibliographies of retrieved references to identify relevant
      associated articles. SELECTION CRITERIA: Papers were selected if the study used a
      health-related database and if the study objectives were to a) use text field to
      identify injury cases or use text fields to extract additional information on
      injury circumstances not available from coded data or b) use text fields to
      assess accuracy of coded data fields for injury-related cases or c) describe
      methods/approaches for extracting injury information from text fields. METHODS:
      The papers identified through the search were independently screened by two
      authors for inclusion, resulting in 41 papers selected for review. Due to
      heterogeneity between studies meta-analysis was not performed. RESULTS: The
      majority of papers reviewed focused on describing injury epidemiology trends
      using coded data and text fields to supplement coded data (28 papers), with these
      studies demonstrating the value of text data for providing more specific
      information beyond what had been coded to enable case selection or provide
      circumstantial information. Caveats were expressed in terms of the consistency
      and completeness of recording of text information resulting in underestimates
      when using these data. Four coding validation papers were reviewed with these
      studies showing the utility of text data for validating and checking the accuracy
      of coded data. Seven studies (9 papers) described methods for interrogating
      injury text fields for systematic extraction of information, with a combination
      of manual and semi-automated methods used to refine and develop algorithms for
      extraction and classification of coded data from text. Quality assurance
      approaches to assessing the robustness of the methods for extracting text data
      was only discussed in 8 of the epidemiology papers, and 1 of the coding
      validation papers. All of the text interrogation methodology papers described
      systematic approaches to ensuring the quality of the approach. CONCLUSIONS:
      Manual review and coding approaches, text search methods, and statistical tools
      have been utilised to extract data from narrative text and translate it into
      useable, detailed injury event information. These techniques can and have been
      applied to administrative datasets to identify specific injury types and add
      value to previously coded injury datasets. Only a few studies thoroughly
      described the methods which were used for text mining and less than half of the
      studies which were reviewed used/described quality assurance methods for ensuring
      the robustness of the approach. New techniques utilising semi-automated
      computerised approaches and Bayesian/clustering statistical methods offer the
      potential to further develop and standardise the analysis of narrative text for
      injury surveillance.

PMID- 20159055
TI  - Age-related safety in professional heavy vehicle drivers: a literature review.
AB  - With Australia facing a looming shortage of heavy vehicle drivers the question is
      raised as to whether it is desirable or prudent to encourage older professional
      heavy vehicle drivers to remain in the transport sector for longer, particularly
      those of heavy vehicles or recruit drivers of a younger age. AIM: To review age
      related safety and identify other factors that contribute to accidents
      experienced by heavy vehicle drivers. METHODS: A search was conducted of national
      and international peer-reviewed literature in the following databases: MedLine,
      Embase, Cinahl, PsychInfo and the Canadian Centre for Occupational Health &
      Safety. A manual search was performed to obtain relevant articles within selected
      journals. RESULTS: A limited number of studies reported age-specific accident
      rates for heavy vehicles for the spectrum of driver age that included drivers
      younger than 27 years and those over 60 years of age. Heavy vehicle drivers
      younger than 27 years of age demonstrated higher rates of accident/fatality
      involvement which decline and plateau until the age of 63 years where increased
      rates were again observed. Other contributing factors to heavy vehicle accidents
      include: long hours and subsequent sleepiness and fatigue, employer safety
      culture, vehicle configuration particularly multiple trailers, urbanisation and
      road classification. CONCLUSIONS: Drivers of heavy vehicles are over-involved
      until age 27 years however a characteristic 'U' shaped curve indicates a higher
      risk of accident involvement for both younger and older drivers. More detailed
      analyses of "at-fault" involvement and inability to avert an accident and other
      factors that contribute to accidents across the ages of heavy vehicle drivers may
      give further clarification to the degree of safety of both younger and older
      commercial heavy vehicle drivers.

PMID- 20159056
TI  - The properties of Safety Performance Indicators in target setting, projections
      and safety design of the road transport system.
AB  - Road traffic Safety Performance Indicators (SPIs) are becoming increasingly used
      as an instrument for the planning and monitoring of safety progress. SPIs form an
      intermediate step between actions and final outcome in terms of casualties in
      road crashes. It is understood that SPIs are closely related to outcome; and that
      it is also possible to use them in calculations and predictions of both actions
      and final outcome. In the present study, it was found that some of the properties
      assigned to SPIs could be questioned. An assumption of linearity between SPIs and
      final outcome was partly rejected. It was also found that 100% fulfillment of a
      set of SPIs could lead to very low mortality, demonstrating the importance of
      handling SPIs simultaneously.

PMID- 20159057
TI  - Reducing traffic speed within roadwork sites using obtrusive perceptual
      countermeasures.
AB  - Excessive speed is currently one of the primary contributory factors in traffic
      accidents within roadwork sites around the world. The present study evaluated two
      novel interventions designed to control traffic speed within an open road,
      roadwork site in New Zealand where drivers were required to decrease their speed
      from 100 to 50km/h. Two different interventions were placed at the entrance to
      the work site and required drivers to pass between a 3.5m wide passage of either
      evenly or decreasingly spaced cones. A multi-element baseline design was
      utilised. Both interventions were highly effective at reducing vehicle speed,
      with the greatest initial decrease in speed to 9.47 km/h below baseline for the
      uneven arrangement. Additionally, both arrangements more than halved the
      proportion of 'dangerous' speeders travelling faster than 20 km/h over the speed
      limit. The findings indicate that both arrangements of cones are effective,
      convenient, cost-effective strategies. It is concluded that, although both
      arrangements are highly effective, the use of unevenly-spaced cones is likely to
      most markedly reduce the number of speed-related accidents within open road
      roadwork zones. The findings are discussed in relation to the perceptual
      mechanisms by which transverse and peripheral stimuli influence speed perception
      and driver behaviour.

PMID- 20159058
TI  - Statistical modelling for falls count data.
AB  - Falls and their injury outcomes have count distributions that are highly skewed
      toward the right with clumping at zero, posing analytical challenges. Different
      modelling approaches have been used in the published literature to describe falls
      count distributions, often without consideration of the underlying statistical
      and modelling assumptions. This paper compares the use of modified Poisson and
      negative binomial (NB) models as alternatives to Poisson (P) regression, for the
      analysis of fall outcome counts. Four different count-based regression models (P,
      NB, zero-inflated Poisson (ZIP), zero-inflated negative binomial (ZINB)) were
      each individually fitted to four separate fall count datasets from Australia, New
      Zealand and United States. The finite mixtures of P and NB regression models were
      also compared to the standard NB model. Both analytical (F, Vuong and bootstrap
      tests) and graphical approaches were used to select and compare models.
      Simulation studies assessed the size and power of each model fit. This study
      confirms that falls count distributions are over-dispersed, but not dispersed due
      to excess zero counts or heterogeneous population. Accordingly, the P model
      generally provided the poorest fit to all datasets. The fit improved
      significantly with NB and both zero-inflated models. The fit was also improved
      with the NB model, compared to finite mixtures of both P and NB regression
      models. Although there was little difference in fit between NB and ZINB models,
      in the interests of parsimony it is recommended that future studies involving
      modelling of falls count data routinely use the NB models in preference to the P
      or ZINB or finite mixture distribution. The fact that these conclusions apply
      across four separate datasets from four different samples of older people
      participating in studies of different methodology, adds strength to this general
      guiding principle.

PMID- 20159059
TI  - Explaining variation in safety performance of roundabouts.
AB  - The conversion of an intersection into a roundabout has been proven to reduce
      generally the number of crashes with injuries or fatalities. However, evaluation
      studies frequently showed considerable individual differences in safety
      performance of roundabouts or particular groups of roundabouts. The main purpose
      in the present study was to explain the variance in safety performance of
      roundabouts through the use of state-of-the-art cross-sectional risk models based
      on crash data, traffic data and geometric data of a sample of 90 roundabouts in
      Flanders-Belgium. Poisson and gamma modelling techniques were used, the latter
      one since underdispersion in the crash data was observed. The results show that
      the variation in crash rates is relatively small and mainly driven by the traffic
      exposure. Vulnerable road users are more frequently than expected involved in
      crashes at roundabouts and roundabouts with cycle lanes are clearly performing
      worse than roundabouts with cycle paths. Confirmation is found for the existence
      of a safety in numbers-effect for bicyclists, moped riders and - with less
      certainty - for pedestrians at roundabouts.

PMID- 20159060
TI  - Factors influencing premature graduation from the use of child restraints in
      Japan.
AB  - This study examined the association of child passenger restraint use by younger
      and older children taking into account situational factors and driver/child
      passenger characteristics. The Japanese national traffic accident data pertaining
      to children injured in rear-end collisions where the drivers were not-at-fault
      was analyzed, while applying the quasi-induced exposure method. Multivariate
      logistic regression analyses were conducted to examine the adjusted effects of
      predictors for proper restraint use by 0-5, 6-9, and 10-12-year-old children.
      Unbelted drivers, child's seating position, the number of total occupants, and
      the child's age were significantly associated with restraint use by both younger
      and older children. Riding in the rear seats was strongly associated with older
      SB-age children not being properly restrained, suggesting a link between the lack
      of booster seat-use requirements and the generally low restraint use rate in rear
      seats as well as the premature graduation from CRS use in general. The results
      were discussed in light of other international findings in this field.

PMID- 20159061
TI  - Functional outcome after road-crash injury: description of the ESPARR victims
      cohort and 6-month follow-up results.
AB  - OBJECTIVE: It is essential to know about the long-term consequences of road
      crashes involving corporal injury in order to adopt relevant public health
      measures. METHODS: The ESPARR cohort comprises 1168 road-crash victims, aged 16
      or over, managed in hospitals in the Rhone administrative department (France). It
      is based on the Registry of Road Traffic Casualties, which has been collecting
      exhaustive data since 1995. Two groups are monitored: mild to moderate (M-AIS 1
      or 2) and severe (M-AIS > or =3). Patients were interviewed at the point of
      primary care, between 1 October 2004 and 31 July 2006. 6 months later, their
      state of health and presence of pain were compared. Multivariate analysis
      (logistic regression) was performed to identify factors related to residual pain.
      RESULTS: Adults of the cohort were compared to the road crash population as a
      whole recorded over the same period in the same area. At 6 months post-accident,
      only 31.9% of victims deemed their health status to have entirely returned to
      normal; 63.8% of mild to moderate and 89.2% of severe cases reported residual
      pain, but neither pain frequency nor intensity correlated with M-AIS. Residual
      pain was related to lower limb injuries (OR=1.6; 95% CI=1.1-2.4). After
      adjustment, pain was essentially related to age, seriousness of the lesions and a
      stay in a rehabilitation unit. CONCLUSION: The ESPARR cohort provides a unique
      opportunity in France to describe the trajectory of a road crash victim, in terms
      both of care and rehabilitation and of resumption of work and personal activity.

PMID- 20159062
TI  - Road traffic crashes on the Yaounde-Douala road section, Cameroon.
AB  - OBJECTIVE: Developing countries account for more than 85% of all road traffic
      deaths in the world. Our aims were to estimate road morbidity and mortality and
      to describe the main characteristics of road traffic crashes on a heavy traffic
      road section in Cameroon. METHODS: We conducted a study of police reports of the
      2004-2007 period retrieved from the 13 police stations in charge of the 243 km
      Yaounde-Douala road section in Cameroon. RESULTS: The estimated overall number of
      people killed per 100 million kilometres driven was 73, more than 35 times higher
      than on similar roads in the US or Europe. The most severe crashes were those
      involving vulnerable road users (97 deaths) and vehicles travelling in opposite
      directions (136 deaths). The main causes of fatal crashes were mechanical
      failures (28%), two-thirds being tyre problems, hazardous overtaking (23%), and
      excessive speed (20%). CONCLUSIONS: The burden of road traffic injuries on heavy
      traffic roads in Cameroon calls for urgent interventions. Traffic calming
      measures and control of vehicle condition appear to be the most cost-effective
      interventions.

PMID- 20159063
TI  - An integrated approach to evaluate policies for controlling traffic law
      violations.
AB  - Modeling dynamics of the driver behavior is a complex problem. In this paper a
      system approach is introduced to model and to analyze the driver behavior related
      to traffic law violations in the Emirate of Abu Dhabi. This paper demonstrates
      how the theoretical relationships between different factors can be expressed
      formally, and how the resulting model can assist in evaluating potential benefits
      of various policies to control the traffic law violations Using system approach,
      an integrated dynamic simulation model is developed, and model is tested to
      simulate the driver behavior for violating traffic laws during 2002-2007 in the
      Emirate of Abu Dhabi. The dynamic simulation model attempts to address the
      questions: (1) "what" interventions should be implemented to reduce and
      eventually control traffic violations which will lead to improving road safety
      and (2) "how" to justify those interventions will be effective or ineffective to
      control the violations in different transportation conditions. The simulation
      results reveal promising capability of applying system approach in the policy
      evaluation studies.

PMID- 20159064
TI  - Evaluation of the HFACS-ADF safety classification system: inter-coder consensus
      and intra-coder consistency.
AB  - This article evaluates an adaptation of the human factors analysis and
      classification system (HFACS) adopted by the Australian Defence Force (ADF) to
      classify factors that contribute to incidents. Three field studies were
      undertaken to assess the reliability of HFACS-ADF in the context of a particular
      ADF air traffic control (ATC) unit. Study one was designed to assess inter-coder
      consensus between many coders for two incident reports. Study two was designed to
      assess inter-coder consensus between one participant and the previous original
      analysts for a large set of incident reports. Study three was designed to test
      intra-coder consistency for four participants over many months. For all studies,
      agreement was low at the level of both fine-level HFACS-ADF descriptors and high
      level HFACS-type categories. A survey of participants suggested that they were
      not confident that HFACS-ADF could be used consistently. The three field studies
      reported suggest that the ADF adaptation of HFACS is unreliable for incident
      analysis at the ATC unit level, and may therefore be invalid in this context.
      Several reasons for the results are proposed, associated with the underlying
      HFACS model and categories, the HFACS-ADF adaptations, the context of use, and
      the conduct of the studies.

PMID- 20159065
TI  - Different perspectives: a comparison of newspaper articles to medical examiner
      data in the reporting of violent deaths.
AB  - This study compared violent death information reported in state-wide newspaper
      articles to the medical examiner reports collected for a state public health
      surveillance system-the National Violent Death Reporting System (NVDRS). While
      suicides accounted for 83% of deaths in the NVDRS database, more than three
      quarters (79%) of violent deaths reported in newspaper articles were homicides.
      The majority of the suicide incidents were reported in 1-2 newspaper articles
      whereas the majority of homicide incidents were reported in 11-34 articles. For
      suicide incidents, the NVDRS reported more circumstances related to mental health
      problems while newspaper articles reported recent crisis more often. Results show
      that there is a mismatch in both frequency and type of information reported
      between a public health surveillance system (NVDRS) and newspaper reporting of
      violent deaths. As a result of these findings, scientists and other public health
      professionals may want to engage in media advocacy to provide newspaper reporters
      with timely and important health information related to the prevention and
      intervention of violent deaths in their community.

PMID- 20159066
TI  - Applying Stafford and Warr's reconceptualization of deterrence theory to drug
      driving: can it predict those likely to offend?
AB  - In December 2007, random roadside drug testing commenced in Queensland,
      Australia. Subsequently, the aim of this study was to explore the preliminary
      impact of Queensland's drug driving legislation and enforcement techniques by
      applying Stafford and Warr's [Stafford, M.C., Warr, M., 1993. A
      reconceptualization of general and specific deterrence. Journal of Research in
      Crime and Delinquency, 30, 123-135] reconceptualization of deterrence theory.
      Completing a comprehensive drug driving questionnaire were 899 members of the
      public, university students, and individuals referred to a drug diversion
      program. Of note was that approximately a fifth of participants reported drug
      driving in the past six months. Additionally, the analysis indicated that
      punishment avoidance and vicarious punishment avoidance were predictors of the
      propensity to drug drive in the future. In contrast, there were indications that
      knowing of others apprehended for drug driving was not a sufficient deterrent.
      Sustained testing and publicity of the legislation and countermeasure appears
      needed to increase the deterrent impact for drug driving.

PMID- 20159067
TI  - Response efficacy: the key to minimizing rejection and maximizing acceptance of
      emotion-based anti-speeding messages.
AB  - This study sought to improve understanding of the persuasive process of emotion
      based appeals not only in relation to negative, fear-based appeals but also for
      appeals based upon positive emotions. In particular, the study investigated
      whether response efficacy, as a cognitive construct, mediated outcome measures of
      message effectiveness in terms of both acceptance and rejection of negative and
      positive emotion-based messages. Licensed drivers (N=406) participated via the
      completion of an on-line survey. Within the survey, participants received either
      a negative (fear-based) appeal or one of the two possible positive appeals (pride
      or humor-based). Overall, the study's findings confirmed the importance of
      emotional and cognitive components of persuasive health messages and identified
      response efficacy as a key cognitive construct influencing the effectiveness of
      not only fear-based messages but also positive emotion-based messages.
      Interestingly, however, the results suggested that response efficacy's influence
      on message effectiveness may differ for positive and negative emotion-based
      appeals such that significant indirect (and mediational) effects were found with
      both acceptance and rejection of the positive appeals yet only with rejection of
      the fear-based appeal. As such, the study's findings provide an important
      extension to extant literature and may inform future advertising message design.

PMID- 20159068
TI  - Ski accidents and legal responsibility: the Spanish case.
AB  - This study classifies and analyzes Spanish court rulings on responsibility for
      ski accidents(1) occurring within ski resort boundaries, and refers to court
      cases to propose guidelines aimed at assisting skiers and ski resort managers.
      Six main trends emerged from the study: (a) Spanish courts resolved lawsuits
      arising from four clearly identifiable categories of ski accidents. (b) Although
      lawsuits involving ski accidents were heard in both civil and criminal
      procedures, civil actions were more extensively brought than criminal ones. (c)
      The majority of the sentences ending legal proceedings resulted in acquittals,
      although the cost to defendants in the minority of cases where convictions were
      made exceeded one million euros in total. (d) No single lawsuit, either civil or
      criminal, was settled in a Court of First Instance; the vast majority were heard
      in Provincial Courts and only a small proportion reached the High Court. (e) The
      defendant was the ski resort operator in the great majority of cases. (f) Court
      decisions were consistently grounded only on the presence or otherwise of the
      factors necessary to prove either damages as a result of negligence, according to
      civil law, or misdemeanor or criminal injuries, in criminal lawsuits.

PMID- 20159069
TI  - The role of substance use and psychosocial characteristics in explaining
      unintentional injuries.
AB  - The objective of this study was to examine the relationship between the use of
      various substances and selected psychosocial characteristics with unintentional
      injury. Cross-sectional data was collected from groups of subjects in treatment
      for a primary problem with cocaine (n=300), cannabis (n=128), alcohol (n=110),
      other drugs (n=35), tobacco (n=249), or gambling (n=199). Subjects completed a
      self-administered questionnaire that included questions on various psychosocial
      scales (i.e., risk-taking/impulsivity, chronic stress, coping, and social
      supports), frequency of drug and alcohol use, and unintentional injuries in the
      year prior to treatment. For the univariate analyses, both frequency of cocaine
      and cannabis use, risk-taking/impulsivity, stress, and coping were significantly
      related to injuries. For the multivariate analyses, only risk-taking/impulsivity,
      stress, age, and sex were significantly related to injuries. The results provide
      important information regarding factors associated with reported injuries among
      individuals in addiction treatment.

PMID- 20159070
TI  - Modeling the behavior of novice young drivers during the first year after
      licensure.
AB  - Novice young drivers suffer from increased crash risk that translates into over
      representation in road injuries. In order to effectively confront this problem, a
      better understanding of the driving behavior of novice young drivers and of its
      determinants is needed. This study analyzes the behavior of novice young drivers
      within a Graduated Driver Licensing (GDL) program. Data on driving behavior of 62
      novice drivers and their parents, who voluntarily participated in this
      experiment, were collected using in-vehicle data recorders that calculate
      compound risk indices as measures of the risk taking behavior of drivers. Data
      were used to estimate a negative binomial model to identify major determinants
      that affect the driving behavior of young drivers during the first year after
      licensure. Estimation results suggest that the risk taking behavior of young
      drivers is influenced by gender, sensation seeking tendency, driving behavior of
      their parents, amount of supervised driving and level of parental monitoring.

PMID- 20159071
TI  - Accidents in the context of study among university students--a multicentre cross
      sectional study in North Rhine-Westphalia, Germany.
AB  - Knowledge about prevalence and patterns of accidents among university students is
      scarce. The aims of the present health survey were to assess the general
      prevalence of accidents among university students, to describe the specific kinds
      of accidents, and to analyse associated factors. A multicentre cross-sectional
      health survey was conducted at 12 universities and 4 universities of applied
      sciences in North Rhine-Westphalia (NRW), Germany. The response rate was 88%. The
      self-administered questionnaire covered multiple areas of health, behaviours and
      a specific module for accidents. In total, 252 (8.8%) out of 2855 students (aged
      17-26 years) had experienced an accident in the context of their studies.
      Contusions, compressions and strains constituted more than 50% of all kinds of
      injuries, while fractures, irritations, burns or acid burns were reported less
      frequently. The cumulative risk of experiencing an accident was increasing
      linearly with the study duration, indicating an absence of a specific vulnerable
      period. Nearly 60% of all accidents took place during study-related sports
      activities, and about a quarter of all accidents occurred on the way to or from
      university. Only few accidents occurred on university floors, in lecture rooms or
      on stairways. Further studies are needed to assess more in depth the causes of
      accidents and the situation immediately preceding the event before making
      specific recommendations for prevention.

PMID- 20159072
TI  - The problems in determining international road mortality.
AB  - We examined road traffic crash (RTC) fatality rate data for the year 2002 with
      the object of determining which data source offered the most reliable estimates
      for international comparison work. Data from the World Health Organisation (WHO)
      (supplied by national health authorities) and the International Road Federation
      (IRF) (supplied by national transport authorities) was compared. There were large
      discrepancies between the rates reported. Discrepancies may be partially
      explained by the under-reporting of fatalities and by different definitions of
      road fatality. Two methodologies to adjust for these factors in the IRF database
      were examined. Neither brought consensus with the WHO RTC fatality rate for all
      nations. While the WHO provide RTC fatality rates for a wider socio-economic and
      geographical range of nations than the IRF, the methodology used by the WHO to
      produce estimates for the least economically developed nations may lead to over
      estimation of RTC fatality rate. WHO RTC fatality rates were more strongly
      associated with variables that are thought to explain RTC fatality rate. We
      suggest that WHO data may be more suitable than the IRF data for international
      comparison studies. However, it is advisable that data for the least developed
      nations be excluded from such work.

PMID- 20159073
TI  - Lasting effects of short-term training on preschoolers' street-crossing behavior.
AB  - Can short-term training improve preschoolers' knowledge of road-crossing concepts
      as well as behavior in a real traffic situation? Forty children, aged four to
      five years, were assigned to one of four conditions (game, story, song, and
      control). Each condition participated in four 15-min classroom-based lessons over
      four weeks. Two assessments measuring knowledge of street-crossing concepts and
      one assessment measuring behavior on a real street were used to evaluate
      performance at baseline and one week and six months post-training. Children in
      all three experimental conditions showed a significant improvement over the
      control on the two conceptual assessments. Only children in the game condition
      significantly improved their behavior on the street-crossing assessment.
      Furthermore, children in all three experimental conditions retained the same
      levels of improvement at the six-month follow-up. These results demonstrate that
      one hour of training can create lasting improvements on preschool children's
      conceptual knowledge of traffic safety and road-crossing behavior on a real
      street.

PMID- 20159074
TI  - Driver characteristics associated with child safety seat usage in Malaysia: a
      cross-sectional study.
AB  - BACKGROUND: The rapidly motorizing environment in Malaysia has made child
      occupant safety a current public health concern. The usage of child safety seats
      (CSS) is a widely regarded intervention to enhance child occupant safety, yet no
      study has been conducted on CSS in Malaysia. This study aims to determine the CSS
      usage rates in Malaysia and to assess driver characteristics that are associated
      with CSS usage. METHODS: Nine variables - urban versus rural study location, age,
      gender, marital status, educational status, monthly family income, number of
      children present in the vehicle, distance traveled to the study location, and
      attitude - were examined through a cross-sectional study of interviewing drivers
      of 230 vehicles transporting at least one child <10 years of age at the time of
      the study. The vehicles were also observed for whether or not there was a CSS
      present. The interviews were conducted at six sampling locations - three urban
      and three rural - in the state of Melaka. RESULTS: 27.4% of the drivers were
      found to be using at least one CSS at the time of the survey. Among the nine
      variables studied, three of the driver characteristics showed statistical
      significance (p<0.05) with CSS usage: age (p=0.047), educational status
      (p=0.009), and attitude (p=0.009). DISCUSSION: This study begins to create
      knowledge on child occupant safety in Malaysia. The results indicate that
      interventional efforts should focus on educational programs geared toward drivers
      that are less educated or extended family members who inconsistently transport
      young children. Furthermore, any educational efforts could be strongly enhanced
      by legislation mandating the use of CSS. Every effort should be made to
      thoroughly assess the effectiveness of any educational or legislative activities
      that are implemented.

PMID- 20159075
TI  - Older female drivers: an emerging transport safety and mobility issue in
      Australia.
AB  - This paper describes an investigation of safety, mobility and travel patterns in
      a sample of older women drivers and former drivers aged 60 years and over.
      Participants provided information on general health and functional abilities,
      travel and driving patterns, driving experiences and confidence, difficulty with
      and avoidance of driving situations, self-assessment of driving ability, crash
      and infringement history, the process and experiences leading up to stopping
      driving, and satisfaction with current mobility. The sample was a fairly active
      group, travelling frequently and substantial distances, and generally satisfied
      with their level of mobility. Current drivers were strongly interested in keeping
      driving for as long as possible, expressed strong concerns about the prospect of
      stopping driving and reported little evidence of self-regulation. In contrast,
      former drivers were less negative about driving cessation and mostly reported
      successful retirement from driving with few negative mobility consequences.
      Further, a number of relationships between crash involvement and driving
      experience, confidence of being a safe driver, and problems in driving situations
      were found. These findings have added to our understanding of the issues
      concerning the safety and mobility of older women. Implications for the promotion
      of safe driving practices are discussed.

PMID- 20159076
TI  - Correspondence between self-reported and objective measures of driving exposure
      and patterns in older drivers.
AB  - The driving behavior of older adults has been traditionally examined using
      questionnaires and diaries. The accuracy of self-reports has been questioned, and
      in-vehicle recording devices touted as more objective measures of real-world
      driving. The purposes of this study were to replicate and extend prior research
      comparing self-report and actual measures of driving exposure and patterns. Two
      electronic devices were installed in the vehicles of 61 drivers (67-92 years, 59%
      women) who were instructed to drive as usual over 1-week. Participants completed
      trip logs, daily diaries, a questionnaire on usual driving habits, ratings of
      situational driving frequency and avoidance and a follow-up interview. Only 53%
      of the sample attempted to estimate how far they had driven over the week and
      self-estimates were inaccurate (ME=77.5 km; CV=44.5%). Drivers tended to miss a
      significant number of trips and stops in their diaries. Driving behavior over the
      week was fairly consistent with usual practices regarding time of day, driving in
      certain areas, and night driving. However, subjects drove in challenging
      situations more than usual. Triangulating multiple sources of electronic and self
      reported data provided a better understanding about the behavior of older
      drivers.

PMID- 20159077
TI  - Appropriate analysis of CIREN data: using NASS-CDS to reduce bias in estimation
      of injury risk factors in passenger vehicle crashes.
AB  - The Crash Injury Research Engineering Network (CIREN) database contains detailed
      medical and crash information on a large number of severely injured occupants in
      motor vehicle crashes. CIREN's major limitation for stand-alone analyses to
      explore injury risk factors is that control subjects without a given injury type
      must have another severe injury to be included in the database. This leads to
      bias toward the null in the estimation of risk associations. One method to cope
      with this limitation is to obtain information about occupants without a given
      injury type from the National Automotive Sampling System's Crashworthiness Data
      System (NASS-CDS), which is a probability sample of towaway crashes, containing
      similar crash information, but less medical detail. Combining CIREN and NASS-CDS
      in this manner takes advantage of the increased sample size when outcomes are
      available in both datasets; otherwise NASS-CDS can serve as a sample of controls
      to be combined with CIREN cases, possibly under a sensitivity analysis that
      includes and excludes NASS-CDS subjects whose status as a control is uncertain.
      Because CIREN is not a probability sample of crashes that meet its inclusion
      criteria, we develop a method to estimate the probability of selection for the
      CIREN cases using data from NASS-CDS. These estimated probabilities are then used
      to compute "pseudo-weights" for the CIREN cases. These pseudo-weights not only
      allow for reduced bias in the estimation of risk associations, they allow direct
      prevalence estimates to be made using medical outcome data available only in
      CIREN. We illustrate the use of these methods with both simulation studies and
      application to estimation of prevalence and predictors of AIS 3+ injury risk to
      head, thorax, and lower extremity regions, as well as prevalence and predictors
      of acetabular pelvic fractures. Results of these analyses demonstrate combining
      NASS and CIREN data can yield improvements in mean square error and nominal
      confidence interval coverage over analyses that use either the NASS-CDS or the
      CIREN sample alone.

PMID- 20159078
TI  - Bayesian analysis for zero-inflated regression models with the power prior:
      applications to road safety countermeasures.
AB  - We consider zero-inflated Poisson and zero-inflated negative binomial regression
      models to analyze discrete count data containing a considerable amount of zero
      observations. Analysis of current data could be empirically feasible if we
      utilize similar data based on previous studies. Ibrahim and Chen (2000) proposed
      the power prior to incorporate certain information from the historical data
      available from previous studies. The power prior is constructed by raising the
      likelihood function of the historical data to the power a(0), where 0< or =a(0)<
      or =1. The power prior is a useful informative prior in Bayesian inference. We
      estimate regression coefficients associated with several safety countermeasures.
      We use Markov chain and Monte Carlo techniques to execute some computations. The
      empirical results show that the zero-inflated models with the power prior perform
      better than the frequentist approach.

PMID- 20159079
TI  - A genetic programming approach to explore the crash severity on multi-lane roads.
AB  - The study aims at understanding the relationship of geometric and environmental
      factors with injury related crashes as well as with severe crashes through the
      development of classification models. The Linear Genetic Programming (LGP) method
      is used to achieve these objectives. LGP is based on the traditional genetic
      algorithm, except that it evolves computer programs. The methodology is different
      from traditional non-parametric methods like classification and regression trees
      which develop only one model, with fixed criteria, for any given dataset. The LGP
      on the other hand not only evolves numerous models through the concept of
      biological evolution, and using the evolutionary operators of crossover and
      mutation, but also allows the investigator to choose the best models, developed
      over various runs, based on classification rates. Discipulus software was used to
      evolve the models. The results included vision obstruction which was found to be
      a leading factor for severe crashes. Percentage of trucks, even if small, is more
      likely to make the crashes injury prone. The 'lawn and curb' median are found to
      be safe for angle/turning movement crashes. Dry surface conditions as well as
      good pavement conditions decrease the severity of crashes and so also wider
      shoulder and sidewalk widths. Interaction terms among variables like on-street
      parking with higher posted speed limit have been found to make injuries more
      probable.

PMID- 20159080
TI  - Driving styles among young novice drivers--the contribution of parental driving
      styles and personal characteristics.
AB  - As part of the effort to ascertain why young drivers are more at risk for car
      crashes, attention has recently turned to the effects of family, including the
      intergenerational transmission of driving styles from parents to offspring. The
      current study sought to further understanding of the nature and aspects of the
      family influence with the help of Bowen's family systems theory. In Phase 1 of
      the prospective study, 130 young driving students completed questionnaires
      tapping personal and personality measures, and their parents completed driving
      related instruments. In Phase 2, a year after the young drivers had obtained
      their driver's license, they were administered the same questionnaires their
      parents had previously completed. The results show significant correlations
      between the parents' driving styles and those of their offspring a year after
      licensure. Furthermore, differentiation of self and self-efficacy in newly
      acquired driving skills were found to moderate or heighten the similarity between
      the driving styles of parents and their offspring. For young drivers reporting
      anxiety in Phase 1, this was associated with a reported anxious driving style a
      year later. Among young female drivers, anxiety was also associated with a
      reckless and careless style. Higher sensation seeking was related to higher
      reckless driving among young male drivers. The findings are discussed in the
      context of adolescence and the role of the study variables in the development and
      intergenerational transmission of driving styles. In addition to its theoretical
      contribution to the realms of intergenerational transmission in general, and
      young drivers in particular, the study may have practical implications for both
      family therapy and the design of driving interventions.

PMID- 20159081
TI  - A comparative analysis of hotspot identification methods.
AB  - The identification of crash hotspots is the first step of the highway safety
      management process. Errors in hotspot identification may result in the
      inefficient use of resources for safety improvements and may reduce the global
      effectiveness of the safety management process. Despite the importance of using
      effective hotspot identification (HSID) methods, only a few researchers have
      compared the performance of various methods. In this research, seven commonly
      applied HSID methods were compared against four robust and informative
      quantitative evaluation criteria. The following HSID methods were compared: crash
      frequency (CF), equivalent property damage only (EPDO) crash frequency, crash
      rate (CR), proportion method (P), empirical Bayes estimate of total-crash
      frequency (EB), empirical Bayes estimate of severe-crash frequency (EBs), and
      potential for improvement (PFI). The HSID methods were compared using the site
      consistency test, the method consistency test, the total rank differences test,
      and the total score test. These tests evaluate each HSID method's performance in
      a variety of areas, such as efficiency in identifying sites that show
      consistently poor safety performance, reliability in identifying the same
      hotspots in subsequent time periods, and ranking consistency. To evaluate the
      HSID methods, five years of crash data from the Italian motorway A16 were used.
      The quantitative evaluation tests showed that the EB method performs better than
      the other HSID methods. Test results highlight that the EB method is the most
      consistent and reliable method for identifying priority investigation locations.
      The EB expected frequency of total-crashes (EB) performed better than the EB
      expected frequency of severe-crashes (EBs), although the results differed only
      slightly when the number of identified hotspots increased. The CF method
      performed better than other HSID methods with more appealing theoretical
      arguments. In particular, the CF method performed better than the CR method. This
      result is quite alarming, since many agencies use the CR method. The PFI and EPDO
      methods were largely inconsistent. The proportion method performed worst in all
      of the tests. Overall, these results are consistent with the results of previous
      studies. The identification of engineering countermeasures that may reduce
      crashes was successful in all of the hotspots identified with the EB method; this
      finding shows that the identified hotspots can also be corrected. The advantages
      associated with the EB method were based on crash data from one Italian motorway,
      and the relative performances of HSID methods may change when using other crash
      data. However, the study results are very significant and are consistent with
      earlier findings. To further clarify the benefits of the EB method, this study
      should be replicated in other countries. Nevertheless, the study results,
      combined with previous research results, strongly suggest that the EB method
      should be the standard in the identification of hotspots.

PMID- 20159082
TI  - Quasi-induced exposure: the choice of exposure metrics.
AB  - The quasi-induced exposure method is widely used to estimate exposure and risks
      of different groups of drivers and vehicles. Essentially, this method assumes
      that non-at-fault or passive parties in two-vehicle collisions represent a random
      sample of the populations on the road. Most previous works have used the whole
      sample of collisions to estimate exposure. There has been some concern about
      possible biases in quasi-induced estimates. In this paper, we argue that (1)
      biases are mainly due to differences in accident avoidance abilities, speeds and
      injury risks, and (2) because the influence of these three factors on the
      probability of being non-at-fault is not the same for every crash type,
      differences may arise among non-at-fault populations, in which case some crash
      types would provide a more accurate estimate of exposure than others. We explore
      the direction of biases due to speed, accident avoidance ability and injury risk
      in four accident types: accidents between vehicles travelling on different lanes
      in two-way, two-lane undivided roads; accidents between vehicles travelling on
      different lanes on multilane roads; intersection accidents; and accidents between
      vehicles travelling on the same lane. Our analysis shows that more research would
      be needed concerning the effect of speed on head-on crashes on undivided roads,
      and crashes on multilane roads.

PMID- 20159083
TI  - Pedestrians, vehicles, and cell phones.
AB  - With cellular phones and portable music players becoming a staple in everyday
      life, questions have arisen regarding the attentional deficits that might occur
      when such devices are used while performing other tasks. Here, we used a street
      crossing task in an immersive virtual environment to test how this sort of
      divided attention affects pedestrian behavior when crossing a busy street. Thirty
      six participants navigated through a series of unsigned intersections by walking
      on a manual treadmill in a virtual environment. While crossing, participants were
      undistracted, engaged in a hands free cell phone conversation, or listening to
      music on an iPod. Pedestrians were less likely to successfully cross the road
      when conversing on a cell phone than when listening to music, even though they
      took more time to initiate their crossing when conversing on a cell phone (
      approximately 1.5s). This success rate difference was driven largely by failures
      to cross the road in the allotted trial time period (30s), suggesting that when
      conversing on a cell phone pedestrians are less likely to recognize and act on
      crossing opportunities.

PMID- 20159084
TI  - Safety Performance Indicator for alcohol in road accidents--international
      comparison, validity and data quality.
AB  - Safety Performance Indicators, SPIs, are developed for various areas within road
      safety such as speed, car occupant protection, alcohol and drugs, vehicle safety,
      etc. SPIs can be used to indicate the road safety situation and to compare road
      safety performance between countries and over time and to understand the process
      leading to accidents, helping to select the measures to reduce them. This article
      describes an alcohol SPI defined as the percentage of fatalities resulting from
      accidents involving at least one driver impaired by alcohol. The calculation of
      the alcohol SPI for 26 European countries shows that the SPI varies from 4.4% in
      Bulgaria to 72.2% in Italy. These results raise the question if the results
      reflect the real situation or if there is a methodological explanation. To answer
      this question three different studies were carried out: comparison with other
      alcohol SPIs, in-depth studies of data quality in seven selected countries, and a
      study of correlations between the SPI and influencing factors. These studies
      indicate clearly that there is a need to improve quality of the data used for the
      alcohol SPI. Most importantly, the total number of drivers involved in fatal
      accidents, the number tested for alcohol and the number not tested, should be
      reported, in addition to the number of alcohol positive and negative drivers
      among those tested. Until these improvements are made, the validity of this SPI
      seems poor and comparison of the alcohol SPI results across countries should be
      made with caution.

PMID- 20159085
TI  - Work-related versus non-work-related road accidents, developments in the last
      decade in France.
AB  - The aim of this research was to analyze the changes that have affected work
      related road accidents between 1997 and 2006, using police data. The study
      focused on drivers aged between 14 and 64 years. The characteristics considered
      were the age, gender, type of vehicle and occupation of the individuals involved
      and the location, time and severity of the accident. Two periods were compared,
      1997-2000 and 2003-2006. Three types of journey were considered: while at work,
      commuting (going to and from work), and non-work-related. The percentage of all
      accidents which were work-related varied little over the decade (10% while at
      work and 18% while commuting). The accidents that occurred while at work still
      had the lowest fatality rates (1.4% among women and 3.4% among men in 2003-2006).
      Men accounted for the majority of the casualties: 90% of fatalities while at work
      and approximately 80% for the other types of journey. The greatest reduction took
      place in the number of motorists, and this has led to an increase in the
      proportion of motorized two-wheelers both while at work and while commuting. In
      the case of accidents while at work, the professional drivers still had the
      highest risk, craftsmen and shopkeepers were also at higher risk than manual
      workers of both genders and male employees. Extending analysis of this type to
      other European countries would be of major interest both for epidemiological
      monitoring and the prevention of occupational road accidents.

PMID- 20159086
TI  - Risk and preventive factors for fatalities in All-terrain Vehicle Accidents in
      New Zealand.
AB  - All-Terrain Vehicles (ATVs) have been used in agriculture for a few decades now.
      Yet despite their invaluable contribution to the productivity of the agricultural
      industry they are associated with a large number of accidents, many of which
      result in a severe or fatal outcome. The main objective of this study was to
      identify the risk factors for ATV-related fatal injuries in order to support the
      design of effective interventions. Using data held by the Department of Labour,
      the current study analysed 355 cases of serious harm accidents associated with
      ATVs including 45 fatalities. The findings suggest that injuries are more likely
      to occur when accidents involve any of the following: children under the age of
      10; four-wheel drive ATVs; driving downhill; driving on a sealed road; driving
      backwards; or if the ATV rolls sideways. A fatal outcome is more likely to occur
      when ATV accidents end up with the vehicle rolling over and pinning the driver
      underneath. Fatalities were also associated with injuries to the head, neck and
      chest. Being employed; and/or having formal training; and/or having brakes and
      tyres well maintained on the ATV; and/or having no fluid load on the ATV reduced
      the risk for fatality. Since the likelihood of a fatal outcome was found to be
      related to human behaviour and ATV rollover, it is suggested that interventions
      should mainly address these two issues.

PMID- 20159087
TI  - Under-reporting of maritime accidents.
AB  - The majority of current maritime regulations has been developed following a
      reactive approach, often as ad-hoc response to serious accidents, and are
      characterised as being prescriptive leaving limited space for adapting equivalent
      solutions rather those described in the regulations. On the premise of providing
      a more proactive approach for the proposal or the evaluation of regulations, the
      Formal Safety Assessment (FSA) has been introduced. In the context of FSA, the
      analysis of accident data is considered to be very important for providing
      potential input on developing more balanced, proactive and cost-effective
      regulations. However, it has been argued that the validity of historical data may
      be undermined by uncertainties. This paper is aimed at showing evidence on
      serious under-reporting in accident databases, which can be considered as the
      main contributor to questioning the direct and uncritical use of historical data.
      By analysing the 10-year tanker accident data from the Lloyd's Register FairPlay
      (LRFP) and the Norwegian Maritime Directorate (NMD) for vessels registered in
      Norway, it is found that the reporting performance has an upper bound of 41% for
      NMD and 30% for LRFP. Furthermore, based on comparison between LRFP data and self
      assessment by Flag States, it is seen that accidents reported by the Flag States
      are also incomplete.

PMID- 20159088
TI  - Impact of traffic oscillations on freeway crash occurrences.
AB  - Traffic oscillations are typical features of congested traffic flow that are
      characterized by recurring decelerations followed by accelerations (stop-and-go
      driving). The negative environmental impacts of these oscillations are widely
      accepted, but their impact on traffic safety has been debated. This paper
      describes the impact of freeway traffic oscillations on traffic safety. This
      study employs a matched case-control design using high-resolution traffic and
      crash data from a freeway segment. Traffic conditions prior to each crash were
      taken as cases, while traffic conditions during the same periods on days without
      crashes were taken as controls. These were also matched by presence of
      congestion, geometry and weather. A total of 82 cases and about 80,000 candidate
      controls were extracted from more than three years of data from 2004 to 2007.
      Conditional logistic regression models were developed based on the case-control
      samples. To verify consistency in the results, 20 different sets of controls were
      randomly extracted from the candidate pool for varying control-case ratios. The
      results reveal that the standard deviation of speed (thus, oscillations) is a
      significant variable, with an average odds ratio of about 1.08. This implies that
      the likelihood of a (rear-end) crash increases by about 8% with an additional
      unit increase in the standard deviation of speed. The average traffic states
      prior to crashes were less significant than the speed variations in congestion.

PMID- 20159089
TI  - Recidivist drink drivers' self-reported reasons for driving whilst unlicensed--a
      qualitative analysis.
AB  - AIM: This paper presents qualitative data from an in-depth interview study of 40
      repeat drink drivers in Perth Western Australia to inform countermeasures for
      these high risk offenders. BACKGROUND: Licence sanctions are effective
      countermeasures for most drink drivers but the small group of repeat offenders
      are less responsive. Many choose to drive whilst unlicensed as the probability of
      detection is low and the social and economic costs of not driving can be high.
      This undermines other drink drive countermeasures. RESULTS: Most respondents who
      had had their licence suspended admitted to driving whilst under suspension.
      Employment and social factors were key themes emerging in respondents' accounts
      of driving whilst under licence suspension. CONCLUSIONS: Whilst a range of
      enforcement countermeasures are needed to deter drunk and unlicensed driving,
      this study suggests that where possible we aim to keep offenders within the
      system that consists of formal laws and informal social controls, rather than
      apply penalties in ways that undermine adherence to the law by increasing
      unlicensed driving. Allowing for interlock installation early in the driving
      suspension period, and allowing fines to offset cost of interlock installation
      and monitoring, may maximise community benefit and reduce unlicensed driving.

PMID- 20159090
TI  - Risk and protection factors in fatal accidents.
AB  - This paper aims at addressing the interest and appropriateness of performing
      accident severity analyses that are limited to fatal accident data. Two
      methodological issues are specifically discussed, namely the accident-size
      factors (the number of vehicles in the accident and their level of occupancy) and
      the comparability of the baseline risk. It is argued that - although these two
      issues are generally at play in accident severity analyses - their effects on,
      e.g., the estimation of survival probability, are exacerbated if the analysis is
      limited to fatal accident data. As a solution, it is recommended to control for
      these effects by (1) including accident-size indicators in the model, (2)
      focusing on different sub-groups of road-users while specifying the type of
      opponent in the model, so as to ensure that comparable baseline risks are worked
      with. These recommendations are applied in order to investigate risk and
      protection factors of car occupants involved in fatal accidents using data from a
      recently set up European Fatal Accident Investigation database (Reed and Morris,
      2009). The results confirm that the estimated survival probability is affected by
      accident-size factors and by type of opponent. The car occupants' survival
      chances are negatively associated with their own age and that of their vehicle.
      The survival chances are also lower when seatbelt is not used. Front damage, as
      compared to other damaged car areas, appears to be associated with increased
      survival probability, but mostly in the case in which the accident opponent was
      another car. The interest of further investigating accident-size factors and
      opponent effects in fatal accidents is discussed.

PMID- 20159091
TI  - Using a reliability process to reduce uncertainty in predicting crashes at
      unsignalized intersections.
AB  - The negative binomial (NB) model has been used extensively by traffic safety
      analysts as a crash prediction model, because it can accommodate the over
      dispersion criterion usually exhibited in crash count data. However, the NB model
      is still a probabilistic model that may benefit from updating the parameters of
      the covariates to better predict crash frequencies at intersections. The
      objective of this paper is to examine the effect of updating the parameters of
      the covariates in the fitted NB model using a Bayesian updating reliability
      method to more accurately predict crash frequencies at 3-legged and 4-legged
      unsignalized intersections. For this purpose, data from 433 unsignalized
      intersections in Orange County, Florida were collected and used in the analysis.
      Four Bayesian-structure models were examined: (1) a non-informative prior with a
      log-gamma likelihood function, (2) a non-informative prior with an NB likelihood
      function, (3) an informative prior with an NB likelihood function, and (4) an
      informative prior with a log-gamma likelihood function. Standard measures of
      model effectiveness, such as the Akaike information criterion (AIC), mean
      absolute deviance (MAD), mean square prediction error (MSPE) and overall
      prediction accuracy, were used to compare the NB and Bayesian model predictions.
      Considering only the best estimates of the model parameters (ignoring
      uncertainty), both the NB and Bayesian models yielded favorable results. However,
      when considering the standard errors for the fitted parameters as a surrogate
      measure for measuring uncertainty, the Bayesian methods yielded more promising
      results. The full Bayesian updating framework using the log-gamma likelihood
      function for updating parameter estimates of the NB probabilistic models resulted
      in the least standard error values.

PMID- 20159092
TI  - Risks of visiting snow destinations: an analysis of skiers' views.
AB  - Very little research exists regarding the risks of visiting snow destinations.
      This study attempts to bridge this gap through insights into skiers' perceptions
      of risk, of great relevance to snow industry stakeholders, by identifying factors
      that influence skiers. The research was conducted in the Spanish Pyrenees, using
      information gathered from adult members of two ski clubs that regularly visit
      this snow destination. Skiing risks, accommodation risks and public safety risks
      were found to have the most important bearing on visitors' risk perceptions.
      However, actual figures demonstrate that respondents had some difficulties in
      assessing the typicality of the risk items and tended to misjudge the true level
      of the risks.

PMID- 20159093
TI  - Injury thresholds after motor vehicle crash--important factors for patient triage
      and vehicle design.
AB  - INTRODUCTION: The Committee on Trauma recommends that older motor vehicle crash
      (MVC) victims or victims of crashes with significant vehicle intrusion of more
      than 12 in. be transferred to a trauma center since those older than 55 have an
      increased risk of death after injury. Yet, the precise injury thresholds as they
      relate to age, gender and velocity remain ill-defined. To maintain a low rate of
      under triage, reliable methods to identify patients at moderate injury risk are
      needed. We therefore characterized the likelihood of moderate to severe injury in
      MVC victims to determine the influence of age, gender and velocity. METHODS: An
      analysis of drivers from the National Automotive Sampling System (1993-2001) was
      performed. Weighted logistic regression models were developed to predict the
      probability of head, leg, and torso injuries as a function of vehicle speed, age,
      and gender while controlling for confounders. A 10% probability of injury
      threshold was set and differences in velocity, gender and age were identified in
      terms of reaching this probability of injury threshold. RESULTS: The analysis
      yielded 56,459 drivers which is equivalent to a population of 28,877,696 drivers
      nationwide. Restraint use, steering away prior to impact, breaking maneuver,
      gender, delta velocity, driver height and age were independent predictors of
      injury. Women had a higher velocity injury threshold than men for the 10%
      probability of injury cut-off to the torso or head which disappeared with
      increasing age. Conversely, men had a higher velocity injury threshold than women
      for the 10% probability of injury cut-off to the extremity which persisted even
      in older victims. CONCLUSIONS: Our data indicate that age and gender must be
      considered in addition to crash velocity when making triage decisions.
      Furthermore, Federal Motor Vehicle Safety Standards may need to be modified to
      address the increased risk of injury among older adults at lower velocities given
      the increasing number of elderly drivers in the US.

PMID- 20159094
TI  - Development of planning level transportation safety tools using Geographically
      Weighted Poisson Regression.
AB  - A common technique used for the calibration of collision prediction models is the
      Generalized Linear Modeling (GLM) procedure with the assumption of Negative
      Binomial or Poisson error distribution. In this technique, fixed coefficients
      that represent the average relationship between the dependent variable and each
      explanatory variable are estimated. However, the stationary relationship assumed
      may hide some important spatial factors of the number of collisions at a
      particular traffic analysis zone. Consequently, the accuracy of such models for
      explaining the relationship between the dependent variable and the explanatory
      variables may be suspected since collision frequency is likely influenced by many
      spatially defined factors such as land use, demographic characteristics, and
      traffic volume patterns. The primary objective of this study is to investigate
      the spatial variations in the relationship between the number of zonal collisions
      and potential transportation planning predictors, using the Geographically
      Weighted Poisson Regression modeling technique. The secondary objective is to
      build on knowledge comparing the accuracy of Geographically Weighted Poisson
      Regression models to that of Generalized Linear Models. The results show that the
      Geographically Weighted Poisson Regression models are useful for capturing
      spatially dependent relationships and generally perform better than the
      conventional Generalized Linear Models.

PMID- 20159095
TI  - Using the U.S. National Household Travel Survey to estimate the impact of
      passenger characteristics on young drivers' relative risk of fatal crash
      involvement.
AB  - Motor vehicle crashes are the main cause of morbidity and mortality in teenagers
      and young adults in the United States. Driving exposure and passenger presence,
      which can both vary by driver and passenger characteristics, are known to
      influence crash risk. Some studies have accounted for driving exposure in
      calculating young driver fatal crash risk in the presence of passengers, but none
      have estimated crash risk by driver sex and passenger age and sex. One possible
      reason for this gap is that data collection on driving exposure often precludes
      appropriate analyses. The purpose of this study was to examine, per 10 million
      vehicle trips (VT) and vehicle-miles traveled (VMT), the relative risk of fatal
      crash involvement in 15-20-year-old male and female drivers as a function of
      their passenger's age and sex, using solo driving as the referent. The Fatality
      Analysis Reporting System provided fatal motor vehicle crash data from 1999 to
      2003 and the 2001 National Household Travel Survey (NHTS) provided VT and VMT.
      The NHTS collects driving exposure for both household and non-household members
      (e.g., friends, colleagues), but demographic characteristics only on household
      members. Missing age and sex of non-household passengers were imputed with hot
      deck using information from household passengers' trips with non-household
      drivers, thereby enabling the calculation of crash rate and relative risk
      estimates based upon driver and passenger characteristics. Using this approach,
      the highest risk was found for young male drivers with 16-20-year-old passengers
      (relative risk [RR] per 10 million VT=7.99; 95% confidence interval [CI], 7.34
      8.69; RR per 10 million VMT=9.94; 95% CI, 9.13-10.81). Relative risk was also
      high for 21-34-year-old passengers, again particularly when both drivers and
      passengers were male. These effects warrant further investigation and underscore
      the importance of considering driving exposure by passenger characteristics in
      understanding crash risk. Additionally, as all imputation techniques are
      imperfect, a more accurate estimation of U.S. fatal crash risk per distance
      driven would require national surveys to collect data on non-household passenger
      characteristics.

PMID- 20159096
TI  - Aviation occupant survival factors: an empirical study of the SQ006 accident.
AB  - We present an empirical study of Singapore Airline (SIA) flight SQ006 to
      illustrate the critical factors that influence airplane occupant survivability.
      The Fuzzy Delphi Method was used to identify and rank the survival factors that
      may reduce injury and fatality in potentially survivable accidents. This is the
      first attempt by a group from both the public and private sectors in Taiwan to
      focus on cabin-safety issues related to survival factors. We designed a
      comprehensive survey based on our discussions with aviation safety experts. We
      next designed an array of important cabin-safety dimensions and then investigated
      and selected the critical survival factors for each dimension. Our findings
      reveal important cabin safety and survivability information that should provide a
      valuable reference for developing and evaluating aviation safety programs. We
      also believe that the results will be practical for designing cabin-safety
      education material for air travelers. Finally, the major contribution of this
      research is that it has identified 47 critical factors that influence accident
      survivability; therefore, it may encourage improvements that will promote more
      successful cabin-safety management.

PMID- 20159097
TI  - Effects of speed limit variation on judged mean speed of a trip.
AB  - Three experiments were set up to study how drivers estimate mean travel speeds on
      trips with different speed limits. To specify, participants judged mean speeds of
      trips with speed limits on different distances of the trip. Study 1 showed that
      the mean speed on a road with a temporary 30 km/h speed limit was overestimated
      if the speeds were greater than 80 km/h on the rest of the trip. Study 2
      replicated and extended the results to problems with more speed combinations. In
      Study 3 the distances of the speed limits were varied and the results showed that
      a temporary 30 km/h speed restriction gave overestimations of the mean speeds of
      a trip for all combinations of original and temporary speed limits over all
      distances. Finally, some psychological issues and applied implications for speed
      regulation policies were discussed.

PMID- 20159098
TI  - The impact of traffic violations on the estimated cost of traffic accidents with
      victims.
AB  - We analyse accidents with victims and calculate the influence of traffic
      violations on the probability of having a serious or fatal accident, compared to
      a slight accident. Traffic violations related to speed limitations,
      administrative infringements or faults related to the driver are considered. Data
      were obtained from all available reports on accidents with victims that occurred
      in Spain from 2003 to 2005. A multinomial logistic regression model is specified
      to find the probability that an accident with victims is slight, serious or
      fatal, given the presence/absence of thirty different types of traffic
      violations. The average cost per victim and the average number of victims per
      accident are then used to find the estimated cost of an accident with victims,
      given the information on the traffic violations incurred. This demonstrates which
      combinations of traffic violations lead to higher estimated average costs,
      compared to cases in which no traffic violation occurred. We conclude with some
      recommendations on the severity of penalties, and suggest that regulators
      penalize the occurrences of some specific combinations of traffic violations more
      rigorously.

PMID- 20159099
TI  - Predicting motorcyclists' intentions to speed: effects of selected cognitions
      from the theory of planned behaviour, self-identity and social identity.
AB  - This study sought to identify cognitive predictors of motorcyclists' intentions
      to speed using a model that comprised selected constructs from the theory of
      planned behaviour (TPB), supplemented with constructs from identity theory and
      social identity theory. Participants (N=110) were sampled from motorcycle clubs
      in Scotland and they completed web-based questionnaire measures of all cognitive
      variables, operationalized with respect to speeding on both 30 mph urban roads
      and 70 mph dual carriageways and motorways. In support of the TPB element of the
      model, affective attitude and perceived controllability accounted for significant
      variance in intention to speed on each road type. The identity constructs
      accounted for additional variance in intentions to speed on 70 mph roads. The
      significant independent predictors of speeding intentions on 30 mph roads were
      affective attitude and perceived controllability. For 70 mph roads, the
      independent predictors of intention were affective attitude, self-identity,
      perceived group norm, group identification, and an interaction between perceived
      group norm and group identification. Consistent with predictions derived from
      social identity theory, decomposition of the interaction showed that perceived
      group norm had an increasing effect on intention with increases in group
      identification. Implications for theory development and safety interventions are
      discussed.

PMID- 20159100
TI  - Gender stereotype conformity and age as determinants of preschoolers' injury-risk
      behaviors.
AB  - Unintentional injuries continue to be a serious public-health problem for
      children and are higher for boys than for girls, from infancy through adulthood.
      Literature on differential socialization concerning risky behaviors and gender
      stereotypes suggests that sex differences in unintentional injuries could be
      explained by children's differential feedback to social pressure, leading to
      behaviors which conform to masculine and feminine stereotypes. We made the
      prediction that boys' and girls' conformity with masculine stereotypes influences
      injury-risk behaviors among preschoolers. Masculinity score, femininity score,
      and injury-risk behaviors of 170 3-6-year old children (89 boys and 81 girls)
      were measured indirectly on two scales filled out by their parents. Results show
      that boys' and girls' injury-risk behaviors are predicted by masculine stereotype
      conformity and that girls' masculine behaviors decline with increasing age. These
      results underline the impact of gender-roles - and of the differential
      socialization associated with those roles - on sex differences in children's
      risky behaviors as early as the preschool period.

PMID- 20159101
TI  - Comparative optimism among drivers: an intergenerational portrait.
AB  - We describe a large cross-sectional study examining comparative optimism (CO)
      regarding the risk of car crash in three age cohorts (17-26, 27-64, 65 and
      older). The participants completed a questionnaire in which they were asked to
      indicate their personal risk of being in an at-fault crash over nine driving
      related events in comparison to young drivers, mid-aged drivers, and older
      drivers. The results indicated that all three age groups exhibited CO, but that
      the level varied according to the age group on which they had to base their
      comparative judgment. Interestingly, greater CO was constantly observed when the
      three age groups compared themselves to older drivers. Also, young males
      exhibited greater CO than female of the same age group.

PMID- 20159102
TI  - Bias properties of Bayesian statistics in finite mixture of negative binomial
      regression models in crash data analysis.
AB  - Factors that cause heterogeneity in crash data are often unknown to researchers
      and failure to accommodate such heterogeneity in statistical models can undermine
      the validity of empirical results. A recently proposed finite mixture for the
      negative binomial regression model has shown a potential advantage in addressing
      the unobserved heterogeneity as well as providing useful information about
      features of the population under study. Despite its usefulness, however, no study
      has been found to examine the performance of this finite mixture under various
      conditions of sample sizes and sample-mean values that are common in crash data
      analysis. This study investigated the bias associated with the Bayesian summary
      statistics (posterior mean and median) of dispersion parameters in the two
      component finite mixture of negative binomial regression models. A simulation
      study was conducted using various sample sizes under different sample-mean
      values. Two prior specifications (non-informative and weakly-informative) on the
      dispersion parameter were also compared. The results showed that the posterior
      mean using the non-informative prior exhibited a high bias for the dispersion
      parameter and should be avoided when the dataset contains less than 2,000
      observations (even for high sample-mean values). The posterior median showed much
      better bias properties, particularly at small sample sizes and small sample
      means. However, as the sample size increases, the posterior median using the non
      informative prior also began to exhibit an upward-bias trend. In such cases, the
      posterior mean or median with the weakly-informative prior provided smaller bias.
      Based on simulation results, guidelines about the choice of priors and the
      summary statistics to use are presented for different sample sizes and sample
      mean values.

PMID- 20159103
TI  - After-action reviews: a venue for the promotion of safety climate.
AB  - This study investigated the role of after-action reviews on perceptions of safety
      climate at the group and organizational levels. Moderated and mediated regression
      analyses of data from 67 firefighting crews suggest that after-action review
      frequency positively influenced both levels of safety climate. Safety-oriented
      group norms fully mediated the relationship between after-action review frequency
      and group-level safety climate. Fire-station busyness moderated the relationship
      between after-action review frequency and organizational-level safety climate,
      such that the relationship was non-existent for highly busy stations. These
      findings suggest that after-action reviews constitute a specific venue through
      which managers can promote safety climate in high-risk environments.

PMID- 20159104
TI  - Bicycle injury events among older adults in Northern Sweden: a 10-year population
      based study.
AB  - Bicycles are a common mode of transportation and injured bicyclists cause a
      substantial burden on the medical sector. In Sweden, about half of fatally
      injured bicyclists are 65 years or older. This study analyzes the injury
      mechanisms, injuries, and consequences among bicyclists 65 years or older and
      compare with younger bicyclists (< or =64) and older adults as passenger car
      drivers, to give a basis for an injury preventive discussion for this age group.
      Umea University Hospital's primary catchments area had 142,000 inhabitants in
      2006. Nearly all injured road users in the well-defined geographic area are
      treated at this hospital and a 10-year data set (N=456) of injured bicyclists
      aged 65+ from the hospital's continuous injury registration (1997-2006) was
      analyzed. The results show that the annual injury incidence was 2.4 and 2.2 per
      1000 men and women, respectively, aged 65 or older. For men the incidence rate
      was constant in the three age groups 65-74, 75-84 and 85+, while it decreased
      strongly for women. The incidence rate for old adults as passenger car drivers
      and younger bicyclists was 1.0 and 4.6, respectively. Most frequent injury
      mechanisms were falls when getting on or off a bicycle (20%) and by potholes or
      irregularities on the ground, edge of a sidewalk, or similar (13%). Only 6% were
      hit by cars, trucks, or buses. Half of the injured suffered fractures or
      dislocations, and 10% suffered concussion or more serious intracranial injuries.
      Getting on or off the bicycle caused most fractures (especially a high fraction
      of the hip and femur fractures) and resulted in 27% of all inpatient days in
      hospital. Three individuals died. One-third of the injured were treated as
      inpatients for a total of 1413 days (on average 9 days), with 69% of the days
      being caused by fractures. The cost for out- and inpatient acute treatment was
      approximately USD 4700 (SEK 33,000) per injured. The results merit an interest
      for this target group; bicycle injuries among older adults are costly both for
      the individual and the medical sector. Injury mitigation strategies focused on
      the needs of this group are probably as well motivated as those focused on older
      car drivers.

PMID- 20159105
TI  - Killer crashes: fatal road traffic accidents in the UK.
AB  - Road traffic accidents are responsible for over 3000 deaths per year in the UK,
      according to Department for Transport (2004a) figures. Although progress is being
      made in a number of areas, vehicle occupant fatalities have not been falling in
      line with casualty reduction targets for the year 2010. A sample of 1185 fatal
      vehicle occupant cases was considered, from ten UK police forces, from the years
      1994-2005 inclusive. The main findings were: (1) over 65% of the accidents
      examined involved driving at excessive speed, a driver in excess of the legal
      alcohol limit, or the failure to wear a seat belt by a fatality, or some
      combination of these. (2) Young drivers have the great majority of their
      accidents by losing control on bends or curves, typically at night in rural areas
      and/or while driving for 'leisure' purposes. These accidents show high levels of
      speeding, alcohol involvement and recklessness. (3) Older drivers had fewer
      accidents, but those fatalities they were involved in tended to involve
      misjudgement and perceptual errors in 'right of way' collisions, typically in the
      daytime on rural rather than urban roads. Blameworthy right of way errors were
      notably high for drivers aged over 65 years, as a proportion of total fatal
      accidents in that age group.

PMID- 20159106
TI  - Driver seat belt use indicates decreased risk for child passengers in a motor
      vehicle crash.
AB  - STUDY OBJECTIVE: We examined the association between driver restraint use and
      child emergency department (ED) evaluation following a motor vehicle crash (MVC).
      METHODS: This cohort study included child passengers aged 0-12 years riding with
      an adult driver aged 21 years or older involved in a MVC in Utah from 1999 to
      2004. The 6 years of Utah MVC records were probabilistically linked to statewide
      Utah ED records. We estimated the relative risk of ED evaluation following a MVC
      for children riding with restrained versus unrestrained drivers. Generalized
      estimating equations were used to calculate relative risks adjusted for child,
      driver, and crash characteristics. RESULTS: Six percent (6%) of children riding
      with restrained adult drivers were evaluated in the ED compared to twenty-two
      percent (22%) of children riding with unrestrained adult drivers following a MVC
      (relative risk 0.29, 95% confidence interval 0.26-0.32). After adjusting for
      child, vehicle, and crash characteristics, the relative risk of child ED
      evaluation associated with driver restraint remained significant (relative risk
      0.82, 95% confidence interval 0.72-0.94). Driver restraint use was associated
      with child restraint use, less alcohol/drug involvement, and lower relative risk
      of severe collision types (head-on, rollover). CONCLUSIONS: Driver seat belt use
      is associated with decreased risk of ED evaluation for child passengers in the
      event of a MVC.

PMID- 20159107
TI  - The SKYNET data: demography and injury reporting in Swedish skydiving.
AB  - BACKGROUND: The Swedish Parachute Association (SFF) national registry of
      skydiving injuries is one of the few trauma databases available for research on
      sport parachuting. The usefulness of this compulsory reporting system may benefit
      from a description of its base population and an evaluation of its sensitivity
      and specificity. METHODS: Cross-sectional analysis based on data collected
      through a web-based questionnaire (SKYNET), from all persons renewing a Swedish
      skydiving license 2008 (n=1049). Sensitivity was measured as the proportion of
      injury events fulfilling the reporting criterion (injury event requiring care of
      a physician) that were actually reported, by comparing the injury events reported
      to the SFF during the skydiving seasons 2006 and 2007 with the injury events
      retrospectively reported to the web-based questionnaire for the same time period.
      Specificity was measured as the proportion of false positives in relation to the
      defined reporting criterion for the same time period. Self-stated bone fractures,
      shoulder dislocations and cruciate ligament injuries were labeled as non-minor
      injuries. Factors affecting the likelihood of reporting were evaluated using
      logistic regression. RESULTS: The response rate was 100%. The overall sensitivity
      of the reporting system 2006/2007 was 0.37 (95% confidence interval (CI) 0.24
      0.51). With self-stated non-minor injuries as the target for reporting, the
      sensitivity was 0.67 (95% CI 0.43-0.85). No significant effect on reporting was
      found for gender, age, license level, years in the sport, total number of jumps
      or club affiliation. The specificity was 0.91 (95% CI 0.83-0.95). Descriptive
      statistics of the Swedish skydiving population show several gender differences.
      CONCLUSIONS: The low sensitivity will yield false low incidence calculations, but
      as there is no evidence for differential underreporting, risk comparisons related
      to the candidate predictor variables appear reasonably valid. The false positive
      reporting warrants assortment of incoming data and a clarification of the
      reporting criteria. Attitudes to reporting may be of value to study, to
      understand the drivers and constraints for achieving a more complete notification
      of skydiving injuries.

PMID- 20159108
TI  - Mapping allele-specific DNA methylation: a new tool for maximizing information
      from GWAS.
AB  - In this issue of The Journal, an article by Schalkwyk et al.(1) shows the
      landscape of allele-specific DNA methylation (ASM) in the human genome. ASM has
      long been studied as a hallmark of imprinted genes, and a chromosome-wide version
      of this phenomenon occurs, in a random fashion, during X chromosome inactivation
      in female cells. But the type of ASM motivating the study by Schalkwyk et al. is
      different. They used a high-resolution, methylation-sensitive SNP array (MSNP)
      method for genome-wide profiling of ASM in total peripheral-blood leukocytes
      (PBL) and buccal cells from a series of monozygotic twin pairs. Their data bring
      a new level of detail to our knowledge of a newly recognized phenomenon
      nonimprinted, sequence-dependent ASM. They document the widespread occurrence of
      this phenomenon among human genes and discuss its basic implications for gene
      regulation and genetic-epigenetic interactions. But this paper and recent work
      from other laboratories(2,3) raises the possibility of a more immediate and
      practical application for ASM mapping, namely to help extract maximum information
      from genome-wide association studies.

PMID- 20159109
TI  - Mutations in the small GTPase gene RAB39B are responsible for X-linked mental
      retardation associated with autism, epilepsy, and macrocephaly.
AB  - Human Mental Retardation (MR) is a common and highly heterogeneous pediatric
      disorder affecting around 3% of the general population; at least 215 X-linked MR
      (XLMR) conditions have been described, and mutations have been identified in 83
      different genes, encoding proteins with a variety of function, such as chromatin
      remodeling, synaptic function, and intracellular trafficking. The small GTPases
      of the RAB family, which play an essential role in intracellular vesicular
      trafficking, have been shown to be involved in MR. We report here the
      identification of mutations in the small GTPase RAB39B gene in two male patients.
      One mutation in family X (D-23) introduced a stop codon seven amino acids after
      the start codon (c.21C > A; p.Y7X). A second mutation, in the MRX72 family,
      altered the 5' splice site (c.215+1G > A) and normal splicing. Neither instance
      produced a protein. Mutations segregate with the disease in the families, and in
      some family members intellectual disabilities were associated with autism
      spectrum disorder, epileptic seizures, and macrocephaly. We show that RAB39B, a
      novel RAB GTPase of unknown function, is a neuronal-specific protein that is
      localized to the Golgi compartment. Its downregulation leads to an alteration in
      the number and morphology of neurite growth cones and a significant reduction in
      presynaptic buttons, suggesting that RAB39B is required for synapse formation and
      maintenance. Our results demonstrate developmental and functional neuronal
      alteration as a consequence of downregulation of RAB39B and emphasize the
      critical role of vesicular trafficking in the development of neurons and human
      intellectual abilities.

PMID- 20159110
TI  - Allelic skewing of DNA methylation is widespread across the genome.
AB  - DNA methylation is assumed to be complementary on both alleles across the genome,
      although there are exceptions, notably in regions subject to genomic imprinting.
      We present a genome-wide survey of the degree of allelic skewing of DNA
      methylation with the aim of identifying previously unreported differentially
      methylated regions (DMRs) associated primarily with genomic imprinting or DNA
      sequence variation acting in cis. We used SNP microarrays to quantitatively
      assess allele-specific DNA methylation (ASM) in amplicons covering 7.6% of the
      human genome following cleavage with a cocktail of methylation-sensitive
      restriction enzymes (MSREs). Selected findings were verified using bisulfite
      mapping and gene-expression analyses, subsequently tested in a second tissue from
      the same individuals, and replicated in DNA obtained from 30 parent-child trios.
      Our approach detected clear examples of ASM in the vicinity of known imprinted
      loci, highlighting the validity of the method. In total, 2,704 (1.5%) of our
      183,605 informative and stringently filtered SNPs demonstrate an average relative
      allele score (RAS) change > or =0.10 following MSRE digestion. In agreement with
      previous reports, the majority of ASM ( approximately 90%) appears to be cis in
      nature, and several examples of tissue-specific ASM were identified. Our data
      show that ASM is a widespread phenomenon, with >35,000 such sites potentially
      occurring across the genome, and that a spectrum of ASM is likely, with
      heterogeneity between individuals and across tissues. These findings impact our
      understanding about the origin of individual phenotypic differences and have
      implications for genetic studies of complex disease.

PMID- 20159111
TI  - Next-generation sequencing of a 40 Mb linkage interval reveals TSPAN12 mutations
      in patients with familial exudative vitreoretinopathy.
AB  - Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous
      retinal disorder characterized by abnormal vascularisation of the peripheral
      retina, often accompanied by retinal detachment. To date, mutations in three
      genes (FZD4, LRP5, and NDP) have been shown to be causative for FEVR. In two
      large Dutch pedigrees segregating autosomal-dominant FEVR, genome-wide SNP
      analysis identified an FEVR locus of approximately 40 Mb on chromosome 7.
      Microsatellite marker analysis suggested similar at risk haplotypes in patients
      of both families. To identify the causative gene, we applied next-generation
      sequencing in the proband of one of the families, by analyzing all exons and
      intron-exon boundaries of 338 genes, in addition to microRNAs, noncoding RNAs,
      and other highly conserved genomic regions in the 40 Mb linkage interval. After
      detailed bioinformatic analysis of the sequence data, prioritization of all
      detected sequence variants led to three candidates to be considered as the
      causative genetic defect in this family. One of these variants was an alanine-to
      proline substitution in the transmembrane 4 superfamily member 12 protein,
      encoded by TSPAN12. This protein has very recently been implicated in regulating
      the development of retinal vasculature, together with the proteins encoded by
      FZD4, LRP5, and NDP. Sequence analysis of TSPAN12 revealed two mutations
      segregating in five of 11 FEVR families, indicating that mutations in TSPAN12 are
      a relatively frequent cause of FEVR. Furthermore, we demonstrate the power of
      targeted next-generation sequencing technology to identify disease genes in
      linkage intervals.

PMID- 20159112
TI  - Mutations in TSPAN12 cause autosomal-dominant familial exudative
      vitreoretinopathy.
AB  - Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder of
      the retinal vascular system. Although mutations in three genes (LRP5, FZD4, and
      NDP) are known to cause FEVR, these account for only a fraction of FEVR cases.
      The proteins encoded by these FEVR genes form part of a signaling complex that
      activates the Norrin-beta-catenin signaling pathway. Recently, through a large
      scale reverse genetic screen in mice, Junge and colleagues identified an
      additional member of this signaling complex, Tspan12. Here, we report that
      mutations in TSPAN12 also cause autosomal-dominant FEVR. We describe seven
      mutations identified in a cohort of 70 FEVR patients in whom we had already
      excluded the known FEVR genes. This study provides further evidence for the
      importance of the Norrin-beta-catenin signaling pathway in the development of the
      retinal vasculature and also indicates that more FEVR genes remain to be
      identified.

PMID- 20159115
TI  - No evidence of skin blisters with human desmocollin-3 gene mutation.

PMID- 20159116
TI  - Perspectives on rehabilitation research.
AB  - Gordon WA. Perspectives on rehabilitation research. The author provides his
      perspectives on both the methodologic and funding challenges faced by
      rehabilitation researchers. His concerns are conveyed about the devaluing of
      rehabilitation research by federal funding agencies and Congress.

PMID- 20159113
TI  - Genome-wide association study in a high-risk isolate for multiple sclerosis
      reveals associated variants in STAT3 gene.
AB  - Genetic risk for multiple sclerosis (MS) is thought to involve both common and
      rare risk alleles. Recent GWAS and subsequent meta-analysis have established the
      critical role of the HLA locus and identified new common variants associated to
      MS. These variants have small odds ratios (ORs) and explain only a fraction of
      the genetic risk. To expose potentially rare, high-impact alleles, we conducted a
      GWAS of 68 distantly related cases and 136 controls from a high-risk internal
      isolate of Finland with increased prevalence and familial occurrence of MS. The
      top 27 loci with p < 10(-4) were tested in 711 cases and 1029 controls from
      Finland, and the top two findings were validated in 3859 cases and 9110 controls
      from more heterogeneous populations. SNP (rs744166) within the STAT3 gene was
      associated to MS (p = 2.75 x 10(-10), OR 0.87, confidence interval 0.83-0.91).
      The protective haplotype for MS in STAT3 is a risk allele for Crohn disease,
      implying that STAT3 represents a shared risk locus for at least two autoimmune
      diseases. This study also demonstrates the potential of special isolated
      populations in search for variants contributing to complex traits.

PMID- 20159117
TI  - The John Stanley Coulter memorial lecture. Anatomy of change: the need for
      effective disability policy change agents.
AB  - The 2009 Coulter Lecture highlights the need for effective disability policy
      change agents to advocate for health care policy and research that focuses on
      optimizing the health and function of individuals with disabilities and chronic
      conditions-not only on their full restoration/cure. The lecture describes the
      "grotesque" historical treatment of persons with disabilities under the old
      policy framework, the treatment of people with disabilities under the
      new/emerging disability policy framework, and the critical role played by
      coalitions in bringing about progressive, sustainable change on behalf of
      individuals with disabilities.

PMID- 20159118
TI  - The business case for adult disability care coordination.
AB  - DESIGN: The study used a retrospective pretest, posttest design of 245
      beneficiaries. Physical impairment ranged from slight to severe. SETTING:
      Minnesota Disability Health Options (MnDHO), a capitated Medicaid program.
      PARTICIPANTS: Medicaid beneficiaries ages 18 to 64 with physical disabilities
      arising from multiple sclerosis, cerebral palsy, spinal cord injury, or brain
      injury. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Change in
      expenditures, rate of return, and utilization. RESULTS: Mean MnDHO monthly
      expenditures including care coordination increased by a factor of 1.75 (P<.001)
      over the previous expenditures. Increasing age has a multiplier effect on
      increased expenditures. Hospitalization rates were unchanged, but the average
      cost per admission and average length of stay dropped significantly (P=.017,
      P=.032, respectively). For people enrolled at least 3 years, annual reductions in
      medical costs more than paid for the added cost of care coordination, but the
      savings in Year 3 were about 20% of the savings in the first 2 years.
      CONCLUSIONS: Care coordination leads to higher program expenditures for enrollees
      with moderate physical impairments who encounter access problems, but has little
      impact on enrollees who are already getting 24-hour care. There is some evidence
      of adverse selection bias. MnDHO's disability care coordination may not be
      financially sustainable over the long term.

PMID- 20159119
TI  - Impact of mental disorders on cost and reimbursement for patients in inpatient
      rehabilitation facilities.
AB  - OBJECTIVE: To determine whether comorbid mental disorders affect inpatient
      rehabilitation facility (IRF) costs and to examine the extent to which Medicare's
      prospective payment system reimbursement sufficiently covers those costs. DESIGN:
      Secondary analysis of Medicare IRF Patient Assessment Instrument files and
      Medicare Provider and Review files. Payment was compared with costs for patients
      with and without reported mood, major depression, substance use, or anxiety
      disorders. The relationships among payment group assignment, comorbidity-related
      adjustments in payment, and the presence of mental disorders were estimated.
      SETTING: IRFs (N=1334) in the United States. PARTICIPANTS: Medicare fee-for
      service beneficiaries (N=1,146,799) discharged from IRFs from 2002 to 2004.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: IRF costs. RESULTS: Mental
      disorders were reported for 13% of the Medicare fee-for-service beneficiaries.
      After controlling for payment group and comorbidity classifications, patients
      with mood, major depression, or anxiety disorders had significantly greater costs
      of $433, $1642, and $247 compared with patients without these disorders. The
      higher cost for patients with major depression (14.9% higher) is sufficient to
      justify a tier 2 comorbidity classification. CONCLUSIONS: A reimbursement
      adjustment for the presence of a major depressive disorder would bring Medicare
      reimbursement in line with facility costs. The failure to compensate facilities
      directly for providing care to patients with major depression may result in
      reduced access to care for these patients. It also may create a disincentive to
      meet mental health treatment needs during the rehabilitative episode. Further
      work is needed to compare costs between patients with and without confirmed
      mental health disorders, given concerns about the accurate reporting of mental
      health disorders.

PMID- 20159120
TI  - Discharge destination's effect on bounce-back risk in Black, White, and Hispanic
      acute ischemic stroke patients.
AB  - OBJECTIVE: To determine whether racial and ethnic effects on bounce-back risk
      (ie, movement to settings of higher care intensity within 30 d of hospital
      discharge) in acute stroke patients vary depending on initial posthospital
      discharge destination. DESIGN: Retrospective analysis of administrative data.
      SETTING: Four hundred twenty-two hospitals, southern/eastern United States.
      PARTICIPANTS: All Medicare beneficiaries 65 years or more with hospitalization
      for acute ischemic stroke within one of the 422 target hospitals during the years
      1999 or 2000 (N=63,679). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Adjusted predicted probabilities for discharge to and for bouncing back from each
      initial discharge site (ie, home, home with home health care, skilled nursing
      facility [SNF], or rehabilitation center) by race (ie, black, white, and
      Hispanic). Models included sociodemographics, comorbidities, stroke severity, and
      length of stay. RESULTS: Blacks and Hispanics were significantly more likely to
      be discharged to home health care (blacks=21% [95% confidence interval (CI), 19.9
      22.8], Hispanic=19% [17.1-21.7] vs whites=16% [15.5-16.8]) and less likely to be
      discharged to SNFs (blacks=26% [95% CI, 23.6-29.3], Hispanics=28% [25.4-31.6] vs
      whites=33% [31.8-35.1]) than whites. However, blacks and Hispanics were
      significantly more likely to bounce back when discharged to SNFs than whites
      (blacks=26% [95% CI, 24.2-28.6], Hispanics=28% [24-32.6] vs whites=21% [20.3
      21.9]). Hispanics had a lower risk of bouncing back when discharged home than
      either blacks or whites (Hispanics=14% [95% CI, 11.3-17] vs blacks=20% [18.4
      22.2], whites=18% [16.8-18.3]). Patients discharged to home health care or
      rehabilitation centers demonstrated no significant differences in bounce-back
      risk. CONCLUSIONS: Racial/ethnic bounce-back risk differs depending on initial
      discharge destination. Additional research is needed to fully understand this
      variation in effect.

PMID- 20159121
TI  - Incidence and profile of inpatient stroke-induced aphasia in Ontario, Canada.
AB  - OBJECTIVES: To determine the incidence rate of inpatient stroke-induced aphasia
      in Ontario, Canada, and to examine the demographic and clinical characteristics
      for stroke patients with and without aphasia. DESIGN: Age- and sex-specific
      incidence rates for aphasia in Ontario were calculated using the Ontario Stroke
      Audit. In addition, data collected from the Registry of the Canadian Stroke
      Network (RCSN) were used to determine the demographic and clinical
      characteristics for stroke patients with and without aphasia. SETTING: All
      hospitals and regional stroke centers in Ontario, Canada. PARTICIPANTS: The
      Ontario Stroke Audit is a representative weighted sample of more than 3000 stroke
      inpatients admitted to emergency departments in all hospitals in Ontario within
      the 2004/2005 fiscal year. RCSN data included a cohort of more than 15,000
      consecutive patients presenting with stroke at 12 regional stroke centers in
      Ontario from 2003 to 2007. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Presence of aphasic symptoms on admission to hospital and at discharge, age and
      sex, stroke type and severity, severity of disability, services received in
      hospital, length of stay, and discharge destination. RESULTS: Thirty-five percent
      (1131/3207) of adult patients admitted with a diagnosis of stroke in the province
      of Ontario during the 2004 to 2005 Ontario Stroke Audit had symptoms of aphasia
      at the time of discharge. This amounts to an incidence rate of 60 per 100,000
      persons per year. Risk of aphasia increased significantly with age. In comparison
      with nonaphasic stroke patients, patients with aphasia were older, presented with
      more severe strokes on admission, had more severe disability, and were more
      frequently discharged to long-term care and/or rehabilitation (unadjusted
      results). Adjusting for stroke severity, age, sex, comorbidity, and stroke
      subtype, the presence of aphasia was found to be an independent predictor of
      longer hospital stays, increased use of rehabilitation services, and higher rates
      of thrombolytic therapy. CONCLUSIONS: A significant number of people with stroke
      experience aphasia, with advancing age associated with a higher risk. The profile
      and patterns for stroke patients with aphasia differed significantly from those
      who did not experience aphasia as a residual disability after stroke,
      particularly in relation to service usage. Given the personal and system cost
      associated with aphasia, best practices in the area of stroke should include
      recommendations on how to best serve this population throughout the clinical
      pathway.

PMID- 20159123
TI  - Effects of aquatic backward locomotion exercise and progressive resistance
      exercise on lumbar extension strength in patients who have undergone lumbar
      diskectomy.
AB  - OBJECTIVE: To compare the effects of aquatic backward locomotion exercise and
      progressive resistance exercise with a machine on lumbar extension strength in
      patients who have undergone diskectomy for a lumbar disk herniation. DESIGN:
      Prospective comparative study. SETTING: Department of Kinesiology at a state
      university. PARTICIPANTS: Male patients (N=30) with disk herniation at spinal
      levels L3 to S1 completed this study as subjects. INTERVENTION: After the
      diskectomy for a lumbar disk herniation, all patients had 6 weeks of rest time.
      At the end of the rest period, the aquatic backward locomotion exercise and
      progressive resistance exercise groups, respectively, started first 6 weeks of
      underwater training and lumbar extension training twice per week. After
      completion of the first 6-week training, subjects participated in a second 6-week
      training. After the whole 12-week training, subjects had no training for 6 weeks
      (detraining) and a follow-up 6-week training (retraining). The control (CON)
      group did not undergo any training. MAIN OUTCOME MEASURES: For each test, maximum
      voluntary isometric lumbar extension strength was measured in 7 trunk positions
      (72 degrees , 60 degrees , 48 degrees , 36 degrees , 24 degrees , 12 degrees ,
      and 0 degrees of the trunk angle). RESULTS: The progressive resistance exercise
      and aquatic backward locomotion exercise groups showed increases in lumbar
      extension strength after the first 6-week training, although they were not
      statistically different from the CON group. After a second 6-week training, the
      progressive resistance exercise and aquatic backward locomotion exercise groups
      showed statistically significant increases in their strength levels as compared
      with the CON group. After the detraining period, the strength levels of the
      progressive resistance exercise and aquatic backward locomotion exercise groups
      did not statistically differ from the CON group. After the retraining period, the
      progressive resistance exercise and aquatic backward locomotion exercise groups
      showed increases in their strength levels, which were different from that of the
      CON group. CONCLUSIONS: The results obtained suggested that the aquatic backward
      locomotion exercise is as beneficial as progressive resistance exercise for
      improving lumbar extension strength in patients after lumbar diskectomy surgery.

PMID- 20159122
TI  - Cognitive and affective predictors of rehabilitation participation after stroke.
AB  - OBJECTIVE: To examine associations between cognitive and affective impairments
      and rehabilitation participation during stroke rehabilitation. DESIGN: Secondary
      analyses of stroke patients who received acetylcholinesterase inhibitors during
      inpatient rehabilitation. SETTING: University-affiliated inpatient rehabilitation
      facilities. PARTICIPANTS: Patients (N=44) admitted to inpatient stroke
      rehabilitation with impairment in attention, memory, or executive functions.
      INTERVENTIONS: Secondary analysis of patients receiving inpatient stroke
      rehabilitation care plus random assignment to one of two acetylcholinesterase
      inhibitors or no drug at rehabilitation admission. MAIN OUTCOME MEASURES:
      Correlations between measures of cognitive (Digit Span, Hopkins Verbal Learning
      Test, Executive Interview) and affective impairments (Hamilton Rating Scale for
      Depression, Apathy Evaluation Scale) and participation (Pittsburgh Rehabilitation
      and Participation Scale) were examined. Significant correlates of participation
      were examined in a linear multiple regression model. RESULTS: Executive functions
      and depressive symptoms were significant correlates of participation. After
      controlling for baseline disability, executive functions predicted participation,
      but depressive symptoms did not (F(4,32)=9.35; R(2)=.54, P<.001). CONCLUSIONS:
      These findings are an important first step toward understanding potentially
      modifiable clinical factors that contribute to rehabilitation participation and
      overall functional status after rehabilitation. A better understanding of
      cognitive impairment and rehabilitation participation may be used to develop
      strategies for improving functional outcomes after stroke.

PMID- 20159124
TI  - Stability limits, single-leg jump, and body awareness in older Tai Chi
      practitioners.
AB  - DESIGN: Cross-sectional study. SETTING: University-based rehabilitation center.
      PARTICIPANTS: Tai Chi practitioners (n=24; age+/-SD, 68.5+/-6.6 y) and control
      subjects (n=20; age, 71.3+/-6.7 y) were recruited. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Measures included the following: (1) subjects' intentional
      weight shifting to 8 different spatial positions within their base of support
      using the limits of stability test, (2) the ability to leave the floor in single
      leg jumping and to maintain balance on landing using force platform measurements,
      and (3) body awareness and movement behaviors using the Body Awareness Scale
      Health (BAS-H). RESULTS: The findings showed that Tai Chi practitioners had a
      significantly better ability to lean further without losing stability and better
      directional control (P<0.01). They had a better ability to jump off the floor
      (P<0.05) and to maintain a longer single-leg stance after landing (P<.05) and
      better overall body awareness (P<.001). The single-leg jumps also correlated
      significantly with limits of stability measures of movement velocity, endpoint
      excursions, and maximum excursions but not with directional control. The BAS-H
      scores correlated significantly with the limits of stability measures except
      directional control. They also correlated significantly with the ability to jump
      off the floor and maintain stability after landing. CONCLUSIONS: When compared
      with healthy controls, Tai Chi practitioners had better stability limits,
      increased ability to perform a single-leg jump, and more stability in landing on
      1 leg as well as better body awareness. Significant correlations among limits of
      stability measures, single-leg jumping tests, and the BAS-H scores indicate the
      importance of body awareness in limits of stability, single-leg jumping, and
      landing.

PMID- 20159125
TI  - Updating the minimal important difference for six-minute walk distance in
      patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To establish the minimal important difference (MID) for the six-minute
      walk distance (6MWD) in persons with chronic obstructive pulmonary disease
      (COPD). DESIGN: Analysis of data from an observational study using distribution-
      and anchor-based methods to determine the MID in 6MWD. SETTING: Outpatient
      pulmonary rehabilitation program at 2 teaching hospitals. PARTICIPANTS: Seventy
      five patients with COPD (44 men) in a stable clinical state with mean age 70
      years (SD 9 y), forced expiratory volume in one second 52% (SD 21%) predicted and
      baseline walking distance 359 meters (SD 104 m). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Participants completed the six-minute walk test before and
      after a 7-week pulmonary rehabilitation program. Participants and clinicians
      completed a global rating of change score while blinded to the change in 6MWD.
      RESULTS: The mean change in 6MWD in participants who reported themselves to be
      unchanged was 17.7 meters, compared with 60.2 meters in those who reported small
      change and 78.4 meters in those who reported substantial change (P=.004). Anchor
      based methods identified an MID of 25 meters (95% confidence interval 20-61 m).
      There was excellent agreement with distribution-based methods (25.5-26.5m,
      kappa=.95). A change in 6MWD of 14% compared with baseline also represented a
      clinically important effect; this threshold was less sensitive than for absolute
      change (sensitivity .70 vs .85). CONCLUSIONS: The MID for 6MWD in COPD is 25
      meters. Absolute change in 6MWD is a more sensitive indicator than percentage
      change from baseline. These data support the use of 6MWD as a patient-important
      outcome in research and clinical practice.

PMID- 20159126
TI  - Validity of clinically derived cumulative somatosensory impairment index.
AB  - DESIGN: Prospective cohort study. SETTING: Population-based cohort. PARTICIPANTS:
      InCHIANTI ("Invecchiare in Chianti" or aging in the Chianti area) study
      participants (N=960; age, 21-91 y, 51.8% women). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The Cumulative Somatosensory Impairment Index was derived
      from baseline performance on clinical tests of pressure sensitivity, vibration
      sensitivity, proprioception, and graphesthesia. Global postural control was
      assessed using Frailty and Injuries Cooperative Studies of Intervention
      Techniques (FICSIT) balance test, time to complete 5 repeated chair stands, and
      fast walking speed, at baseline and at 3-year follow-up. RESULTS: In participants
      without neurologic conditions (n=799), the Cumulative Somatosensory Impairment
      Index was significantly different in age groups classified by decades (P<.001).
      Compared with participants without prevalent conditions, the Cumulative
      Somatosensory Impairment Index was significantly higher in persons with diabetes
      (P=.017), peripheral arterial disease (P=.006), and a history of stroke (P<.001).
      In the overall population (N=960), in the fully adjusted multiple regression
      models, the Cumulative Somatosensory Impairment Index independently predicted
      deterioration in FICSIT scores (P=.002), time for 5 repeated chair stands
      (P<.001), and fast gait speed (P=.003) at 3-year follow-up. CONCLUSIONS: The
      Cumulative Somatosensory Impairment Index is a valid measure that detects
      relevant group differences in lower limb somatosensory impairment and is an
      independent predictor of decline in postural control over 3 years.

PMID- 20159127
TI  - Responsiveness of mobility, daily living, and instrumental activities of daily
      living outcome measures for geriatric rehabilitation.
AB  - OBJECTIVES: To assess and compare the ability of the Timed Up & Go (TUG) and
      subscales of the Functional Autonomy Measurement System (SMAF) to detect change
      in people undergoing geriatric rehabilitation in inpatient geriatric
      rehabilitation units (GRUs) and day hospitals. DESIGN: Longitudinal design with
      repeated measures obtained at admission and discharge from rehabilitation and at
      2 follow-up interviews. SETTING: Inpatient and outpatient hospital-based
      settings. PARTICIPANTS: Subjects (N=237, age 80+/-7 y) had data at admission and
      discharge from rehabilitation (changing time frame), and of these, 160 had data
      at 2 subsequent follow-ups (stable time frame). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The TUG was used to estimate basic mobility, and subscales
      of the SMAF were used to estimate general mobility (SMAF-mobility), basic
      activities of daily living (SMAF-ADL), and instrumental activities of daily
      living (SMAF-IADL). Professionals' perception of change was used as a criterion.
      RESULTS: The TUG generated large values for the standardized response mean (SRM)
      and Guyatt's responsiveness index in GRUs (.98 and 1.12) and day hospitals (.89
      and 1.85). Professionals' perception of change in mobility was explained by a
      perceptible change in the TUG in day hospitals (15%) but not in GRUs. The SMAF
      mobility, SMAF-ADL, and SMAF-IADL were associated with large values of SRM and
      Guyatt's responsiveness index in GRUs (.97-2.17) and with small to moderate
      values in day hospitals (.29-.54). Moderate to large portions in the
      professionals' perceptions of change for mobility (20%, 17%), basic ADLs (10% and
      14%), and IADLs (23% and 19%) were associated with the respective change scores
      of the subscales of the SMAF in both GRUs and day hospitals. CONCLUSIONS:
      Progress of older adults in the areas of mobility, basic ADLs, and IADLs can be
      captured using the TUG, SMAF-mobility, SMAF-ADL, and SMAF-IADL in both GRUs and
      day hospitals. The results support their use in settings of high- and low
      intensity rehabilitation, thus suggesting their adequacy for use in these 2
      settings.

PMID- 20159128
TI  - Predictive validity of the classification schema for functional mobility tests in
      instrumental activities of daily living decline among older adults.
AB  - OBJECTIVE: To determine predictive validity for cut points of the Timed Up & Go
      (TUG) test and life-space assessment (LSA) on decline in instrumental activities
      of daily living (IADLs) among older adults. DESIGN: Cross-sectional and 1-year
      follow-up study. SETTING: Preventive health care services. PARTICIPANTS: In a
      cross-sectional study, 2404 older adults (65-100 y) were recruited to determine
      cut points for the TUG and LSA for IADLs limitation. For longitudinal analysis,
      436 older adults (65-100 y) were followed over 1 year to explore the validity of
      a classification model using the cut points to predict incident IADLs decline.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The TUG, LSA, and Tokyo
      Metropolitan Institute of Gerontology index of IADLs measurement. RESULTS: The
      cut points associated with IADLs limitations for the TUG and LSA were 12 seconds
      and 56 points, respectively. Participants were classified into fast/high (most
      able; TUG <12 and LSA >56), fast/low, slow/high, and slow/low (vulnerable; TUG >
      or =12 and LSA < or =56) groups; there were 813 (34%), 385 (16%), 246 (10%), and
      960 (40%) participants in each group, respectively. The proportions of
      participants with IADLs limitation in the most able, fast/low, slow/high, and
      vulnerable groups were 19%, 64%, 61%, and 89%, respectively. The vulnerable group
      included significantly more participants with IADLs limitation than any other
      group (P<.001). Compared with a most able group, the odds ratios of IADLs decline
      for the fast/low and vulnerable groups were 2.52 (95% confidence interval 1.15
      5.53, P<.05) and 2.87 (95% confidence interval 1.38-5.96, P<.01), respectively.
      CONCLUSIONS: The combination of TUG and LSA identifies persons with future IADLs
      decline and has the potential to be used by community health care services to
      target individualized interventions.

PMID- 20159129
TI  - Long-term outcome of patients discharged to a nursing home after aneurysmal
      subarachnoid hemorrhage.
AB  - OBJECTIVE: To study long-term outcome in patients with aneurysmal subarachnoid
      hemorrhage (SAH) who are relatively young. DESIGN: Retrospective cohort study.
      SETTING: Nursing homes. PARTICIPANTS: Patients with SAH (N=92) admitted to our
      hospital from 1996 to 2006 who were discharged to a nursing home. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Death, discharge from nursing home, and
      functional status at end of follow-up. RESULTS: Of the 92 patients included, 45
      had died after a median of 1.1 years (range, 0.0-8.5 y), 35 were discharged to
      home or a sheltered housing or rehabilitation center after a median of 0.6 years
      (range, 0.1-9.6 y), and 12 remained in a nursing home after a median of 4.8 years
      (range, 2.2-12.0 y). Forty-four (43%) had survived longer than 5 years, and 29
      (31%) had regained functional independence within the initial 2 years after
      admission to the nursing home. Early discharge tended to occur more often in
      patients admitted from 2001 to 2006 than in those admitted from 1996 to 2001
      (hazard ratio=1.8; 95% confidence interval, 0.9-3.7) and in those with an
      aneurysm not in the anterior communicating artery (hazard ratio=1.9; 95%
      confidence interval, 0.9-3.9). CONCLUSIONS: The prognosis for patients with SAH
      after admission to a nursing home is not gloomy. The type of rehabilitation that
      offers best chances to these patients needs to be investigated.

PMID- 20159130
TI  - Actual reality: a new approach to functional assessment in persons with multiple
      sclerosis.
AB  - OBJECTIVE: To examine the use of an innovative approach for assessing everyday
      life activities of people with multiple sclerosis (MS): Actual Reality. Actual
      Reality is a performance-based assessment approach that involves the use of the
      internet to perform real, everyday life activities. DESIGN: A between-subjects
      design. SETTING: Outpatient rehabilitation institute. PARTICIPANTS: Persons
      (n=21) with clinically definite MS and healthy controls (HCs) (n=18) without any
      reported neurologic disabilities participated in this study. Participants were
      between the ages of 21 to 60 years, and the sample consisted of volunteer sample.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants were asked to
      access the internet to purchase airline tickets for a round trip flight and were
      administered the Minimal Assessment of Cognitive Functioning in Multiple
      Sclerosis. Participants also completed questionnaires to assess quality of life
      (Functional Assessment of Multiple Sclerosis), functional status (Functional
      Behavior Profile), and prior Internet experience. RESULTS: The MS group displayed
      significantly more difficulties than the HC group in accurately and independently
      completing the Actual Reality task primarily because of cognitive impairment.
      Self-report of quality of life and functional status were not correlated with
      Actual Reality performance in the group of people with MS. However, the self
      report measures were significantly associated with affective symptomatology.
      CONCLUSIONS: These results provide initial evidence supporting the use of the
      Actual Reality approach in assessing persons with MS performing everyday life
      activities. Actual Reality is a significant step forward in increasing the
      sensitivity, accessibility, and relevancy of functional assessments in people
      with cognitive and physical disabilities.

PMID- 20159131
TI  - Step counting and energy expenditure estimation in patients with chronic
      obstructive pulmonary disease and healthy elderly: accuracy of 2 motion sensors.
AB  - OBJECTIVE: To compare the accuracy of 2 motion sensors (a pedometer and a
      multisensor) in terms of step counting and estimation of energy expenditure (EE)
      in patients with chronic obstructive pulmonary disease (COPD) and in healthy
      elderly. DESIGN: In this descriptive study, all participants wore both motion
      sensors while performing a treadmill walking protocol at 3 different speeds
      corresponding to 30%, 60%, and 100% of the average speed achieved during a six
      minute walk test. As criterion methods, EE was estimated by indirect calorimetry,
      and steps were registered by videotape. SETTING: Research laboratory at a
      university hospital. PARTICIPANTS: Patients with COPD (n=30; 17 men; mean age +/-
      SD, 67+/-8 y; mean forced expiratory volume in the first second [FEV(1)]
      predicted +/- SD, 46%+/-17%; mean body mass index [BMI] +/- SD, 24+/-4 kg.m(2))
      and matched healthy elderly (n=30; 15 men; mean age +/- SD, 68+/-7 y; mean FEV(1)
      predicted +/- SD, 104%+/-21%; mean BMI +/- SD, 25+/-3 kg.m(2)). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURE: Step counting and EE estimation during a
      treadmill walking protocol. RESULTS: The pedometer was accurate for step counting
      and EE estimation in both patients with COPD and healthy elderly at the higher
      speed. However, it showed significant underestimation at the 2 slower speeds in
      both groups. The multisensor did not detect steps accurately at any speed,
      although it accurately estimated EE at all speeds in healthy elderly and at the
      intermediate and higher speeds in patients with COPD. CONCLUSIONS: In both
      patients with COPD and healthy elderly, the multisensor showed better EE
      estimates during most walking speeds than the pedometer. Conversely, for step
      counting, accuracy is observed only with the pedometer during the higher walking
      speed in both groups.

PMID- 20159132
TI  - Power wheelchair prescription, utilization, satisfaction, and cost for patients
      with amyotrophic lateral sclerosis: preliminary data for evidence-based
      guidelines.
AB  - OBJECTIVES: To determine the features most frequently selected in a power
      wheelchair (PWC), level of satisfaction with the selections, and how often the
      PWC features are used by patients diagnosed with amyotrophic lateral sclerosis
      (ALS)/motor neuron disease (MND). DESIGN: Internally generated questionnaire.
      SETTING: An ALS/Muscular Dystrophy Association center. PARTICIPANTS: Convenience
      sample of current patients (N=45) of our clinic with ALS/MND who are PWC users
      (men, n=27; women, n=18; age range, 27-85 y). INTERVENTION: Self-administered
      survey. MAIN OUTCOME MEASURE: Thirty-two patients completed a 31-question survey
      investigating patients' patterns of selection, satisfaction, and frequency of PWC
      use; technical and psychometric influences; and other aspects of decision-making
      processes that patients experience before, during, and after acquiring a PWC.
      RESULTS: Ninety percent of respondents received their evaluations at a
      multidisciplinary ALS clinic, 1 via the Department of Veterans Affairs, and 1 was
      unknown. Sixty-six percent of patients thought the chair evaluation was timed
      correctly, and 19% wished they had started sooner. Forty-five percent of people
      were able to walk a few steps, and 55% were able to stand when their chairs
      arrived. When they first received the chair, 79% were satisfied with the overall
      comfort of the chair, and 86% were satisfied with the ease of use; currently, 69%
      are satisfied with the overall comfort, and 72% are satisfied with ease of use.
      There was a statistically significant difference in how patients used their
      wheelchair features initially and currently in terms of seat elevate and
      attendant control, but not tilt, recline, and elevating leg rests. The average
      cost for the power chairs was $26,404 (range, $19,376-$34,311), and the average
      cost a month is $917. Overall, 88% of respondents said they would get the same
      type of chair with the same features again, and 81% felt that the chair was a
      good value for the cost. CONCLUSIONS: We obtained first-hand knowledge from 32
      patients with ALS/MND who are current PWC users on their use and satisfaction
      with their PWCs from initial to current use. Based on this survey, patients with
      ALS/MND seen for their wheelchair evaluation with experienced clinicians exhibit
      high use and satisfaction with their PWCs.

PMID- 20159133
TI  - Relationship between perceived exertion and physiologic markers during arm
      exercise with able-bodied participants and participants with poliomyelitis.
AB  - OBJECTIVE: To investigate the strength of the relationship between ratings of
      perceived exertion (RPE) and oxygen uptake (Vo(2)), heart rate, ventilation (Ve)
      and power output (PO) during an arm-crank ramped exercise test to volitional
      exhaustion in men and women who differed in physical status. DESIGN: Each
      participant completed an arm-crank ramp exercise test to volitional exhaustion.
      PO was increased by 15 W.min(-1) and 6 W.min(-1) for men and women able-bodied
      participants, respectively; for the poliomyelitis participants, 9 W.min(-1) and 6
      W.min(-1) increments were used for men and women, respectively. SETTING:
      Laboratory facilities at a university. PARTICIPANTS: Able-bodied participants
      (n=16; 9 men, 7 women) and participants with poliomyelitis (n=15, 8 men, 7 women)
      volunteered for the study. MAIN OUTCOME MEASURES: Strength of the relationship
      (R(2) values) between RPE and Vo(2), heart rate, Ve and PO. RESULTS: There were
      significantly higher values for maximum Vo(2) and maximum PO for able-bodied men
      compared with their counterparts with poliomyelitis (P<.05). However, when the
      data were controlled for age, there were no significant differences in these
      values (P>.05). Similar results were observed for the women who were able-bodied
      as well as for the women who had poliomyelitis (P>.05). The relationships between
      heart rate and RPE and Ve and RPE for able-bodied patients and patients with
      poliomyelitis were similar (R(2)>.87). The relationship between Vo(2) and RPE was
      stronger in the able-bodied participants compared wih the participants with
      poliomyelitis, regardless of sex (P<.05). However, when the data were controlled
      for age, there was no significant difference in the strength of this relationship
      between able-bodied participants and those with poliomyelitis, regardless of sex
      (P>.05). CONCLUSIONS: RPE is strongly related to physiologic markers of exercise
      intensity during arm exercise, irrespective of sex or participant's poliomyelitis
      status.

PMID- 20159134
TI  - Evaluating displacement of the coracoacromial ligament in painful shoulders of
      overhead athletes through dynamic ultrasonographic examination.
AB  - OBJECTIVE: To evaluate displacement of the coracoacromial ligament (CAL), using
      dynamic ultrasonography (US), for detecting instability-related impingement
      caused by overhead activities. DESIGN: Between-group survey. SETTING: Department
      of Physical Medicine and Rehabilitation in a tertiary care center. PARTICIPANTS:
      Volunteer high school volleyball players with unilateral shoulder pain (n=10) and
      volunteer asymptomatic high school volleyball players with identical training
      activities as control subjects (n=16). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: The displacement of the CAL was measured during throwing
      simulation using dynamic US. Both shoulders of all subjects were evaluated.
      RESULTS: During throwing simulation, the displacement of the CAL in the painful
      shoulders of overhead athletes increased significantly greater than the
      displacement in the asymptomatic shoulder (3.0+/-0.7 mm and 2.2+/-0.4 mm,
      respectively; P=.017). No difference was identified between the displacements of
      the CALs of bilateral shoulders of the control group subjects. CONCLUSIONS:
      Dynamic US, by measuring the displacement of the CAL during simulation of
      throwing, may be helpful in detecting abnormal humeral head upward migration in
      overhead athletes.

PMID- 20159135
TI  - Needle insertion into the tibialis posterior: ultrasonographic evaluation of an
      anterior approach.
AB  - OBJECTIVE: To investigate the ultrasonographic anatomy of the lower leg for safe
      and accurate needle placement into the tibialis posterior using the anterior
      approach. DESIGN: Cross-sectional study. SETTING: University rehabilitation
      hospital. PARTICIPANTS: Healthy volunteers (N=62; 30 men, 32 women).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The safety window (the
      tibia to the neurovascular bundle) and the depth to the midpoint of the safety
      window (skin to the tibialis posterior) at the upper third and the midpoint of
      the tibia were measured with a transverse ultrasonographic scan. RESULTS: The
      safety window at the upper third of the tibia was significantly larger than that
      at the midpoint (P<.01). The safety window ranged from .64 cm to 2.13 cm at the
      upper third tibialis point and from .32 cm to 1.30 cm at the midpoint. The depth
      to the tibialis posterior at the upper third of the tibia was significantly
      deeper than that in the midpoint (P<.01). The depth ranged from 2.47 cm to 4.66
      cm at the upper third tibias point and from 2.35 cm to 4.28 cm at the midpoint.
      CONCLUSIONS: Ultrasonography is a useful tool in measuring the safety window and
      the depth to the tibialis posterior using the anterior approach. Considering the
      safety window, we suggest the needle placement at the upper third point of tibia
      rather than that at the midpoint.

PMID- 20159136
TI  - Monitoring of physical activity after stroke: a systematic review of
      accelerometry-based measures.
AB  - OBJECTIVE: To assess the clinimetric properties and clinical applicability of
      different accelerometry-based measurement techniques in persons with stroke. DATA
      SOURCES: A systematic search of literature was performed using a specific search
      strategy by means of different electronic databases until October 2008 (PubMed,
      EMBASE, CINAHL, Cochrane Library of Clinical Trials). STUDY SELECTION: A first
      selection was made by means of title and abstract. A second selection was
      performed by means of predefined inclusion criteria: (1) accelerometry in stroke
      population, (2) application of accelerometry in patients with stroke including
      clinimetric properties. The exclusion criteria were (1) dysphagia, (2) new
      engineering techniques or software alterations, (3) secondary sources, and (4)
      Case studies. DATA EXTRACTION: The clinimetric properties and applicability of
      accelerometry were described based on the included publications. DATA SYNTHESIS:
      Twenty-five articles (4 randomized controlled trials) were included. The
      information of the publications was divided into (1) gait, cadence, and
      ambulatory activity; (2) upper-extremity activity; and (3) topics related to
      stroke other than upper or lower extremity. Accelerometry was shown to be valid
      and had good test-retest reliability in a large number of settings. Numerous
      studies demonstrated correlations between accelerometry and common stroke scales.
      Trunk movements were measured as an outcome of disturbed gait. The vertical
      asymmetry index especially was able to differentiate between persons with stroke
      and healthy controls. Persons with stroke showed less ambulatory activity,
      measured as steps per day, than sedentary controls. Triaxial accelerometry was
      able to distinguish between varying activity levels. Upper-extremity use was
      lesser in persons with stroke. It was impossible to calculate a minimal clinical
      difference for arm use by a uniaxial accelerometer. Evidence was presented that
      finger-tapping and sit-to-stand measured by accelerometers could be used to
      define recovery from stroke. CONCLUSIONS: The literature concerning accelerometry
      incorporated into stroke research is young, limiting the ability to draw
      consistent conclusions. Nonetheless, the available evidence suggests that
      accelerometers yield valid and reliable data about the physical activity of
      patients with stroke. Future research is necessary to investigate clinimetric
      properties like predictive value and responsiveness further before implementing
      accelerometry in clinical trials as an outcome for change.

PMID- 20159137
TI  - Effectiveness of interventions of specific complaints of the arm, neck, and/or
      shoulder: 3 musculoskeletal disorders of the hand. An update.
AB  - OBJECTIVES: To provide an evidence-based overview of the effectiveness of
      conservative and surgical interventions for trigger finger, Dupuytren's, and De
      Quervain's diseases. DATA SOURCES: The Cochrane Library, PEDro, PubMed, Embase,
      and CINAHL were searched to identify relevant studies. STUDY SELECTION: Two
      reviewers independently applied the inclusion criteria to select potential
      relevant studies from the title and abstracts of the references retrieved by the
      literature search. Relevant (Cochrane) reviews and randomized controlled trials
      (RCTs) were included. DATA EXTRACTION: Two reviewers independently extracted the
      data and performed a methodologic quality assessment. DATA SYNTHESIS: A best
      evidence synthesis was performed to summarize the results of the included trials.
      One Cochrane review (trigger finger) and 13 RCTs (trigger finger [6], Dupuytren's
      [4], De Quervain's [3]) were included. The trials reported on physiotherapy (De
      Quervain's), steroid injections (trigger finger, De Quervain's), surgical
      treatment (trigger finger, De Quervain's), and a postsurgical treatment
      (Dupuytren's). For trigger finger, moderate evidence was found for the
      effectiveness of steroid injections in the short-term (1-4 wk) but not for long
      term outcomes. Limited evidence was found for the effectiveness of staples
      compared with sutures in skin closure and for intermittent compression after
      surgery to treat Dupuytren's disease. For other interventions, no evidence was
      found. CONCLUSIONS: Indications for effectiveness of some interventions for
      trigger finger, Dupuytren's, and De Quervain's diseases were found. Because only
      a few RCTs were identified, it is difficult to draw firm conclusions. High
      quality RCTs are clearly needed in this field.

PMID- 20159138
TI  - Vision and driving in multiple sclerosis.
AB  - OBJECTIVE: To examine the relationship between measures of visual dysfunction and
      driving performance in persons with multiple sclerosis (MS). DESIGN: Between
      group comparison. SETTING: All data were collected in an outpatient research
      setting. PARTICIPANTS: Persons (N=66) with MS of the relapsing remitting type (26
      self-reporting visual difficulties; 40 self-reporting no visual difficulties) and
      26 age- and sex-matched healthy controls. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Measures of vision included visual acuity, depth perception,
      and color perception. Driving was measured using documented accident/violation
      rate and self-reported driving behaviors. RESULTS: Quantitative analysis only
      revealed that MS persons with self-reported visual difficulties performed
      significantly worse than healthy controls on color perception (Kruskal-Wallis;
      chi(2)(2)=8.89, P=.01). There were no group differences on driving behaviors, and
      correlational analysis revealed a lack of relationship between the selected
      visual (visual acuity, depth perception, color perception) and driving
      performance measures (documented accident/violation rate and self-limiting
      driving behaviors). CONCLUSIONS: Persons with MS who self-reported difficulties
      with vision had acceptable visual acuity, despite demonstrating impairment in
      color perception. The fact that visual acuity remains the most common measure for
      visual fitness to drive remains problematic. There is a need to further define
      measures of visual dysfunction relevant to driving among this clinical
      population.

PMID- 20159139
TI  - Ulnar neuropathy with normal electrodiagnosis and abnormal nerve ultrasound.
AB  - Ulnar neuropathy at the elbow (UNE) is the second most common entrapment
      neuropathy. It is diagnosed with electrodiagnostic studies, but they can yield
      false-negative results. Ultrasound was used to examine 4 patients with UNE and
      negative electrodiagnostic findings, and it showed ulnar nerve enlargement near
      the elbow in all cases, with a mean cross-sectional area of 20.1 mm. This
      indicates that ultrasound may be a useful tool for assessing those with UNE
      symptoms and normal electrodiagnostic findings.

PMID- 20159140
TI  - Herpes zoster-induced trunk muscle paresis presenting with abdominal wall
      pseudohernia, scoliosis, and gait disturbance and its rehabilitation: a case
      report.
AB  - Herpes zoster (HZ)-induced abdominal wall pseudohernia has been frequently
      reported, but there has been no report describing HZ-induced trunk muscle paresis
      leading to functional problems. We describe a 73-year-old man with T12 and L1
      segmental paresis caused by HZ presenting with abdominal wall pseudohernia,
      scoliosis, and standing and gait disturbance who responded well to a systematic
      rehabilitation approach. He first noticed a right abdominal bulge in the 6th
      postherpetic week, which was gradually accompanied by right convex thoracolumbar
      scoliosis, pain, and standing and gait disturbance in the 12th week. Needle
      electromyography revealed abnormal spontaneous activities at rest in the right
      T12 myotomal muscles, and motor unit recruitment was markedly decreased. We
      arranged an outpatient rehabilitation program consisting of using a soft
      thoracolumbosacral orthosis for pain relief and trunk stability, muscle
      reeducation of the paretic abdominal muscles, strengthening of the disused trunk
      and extremity muscles, and gait exercise. Based on electromyographic findings, we
      instructed him in an effective method of muscle reeducation. After 4 months of
      rehabilitation, he showed marked improvement and became an outdoor ambulator. We
      suggest that electromyography is a useful tool to evaluate clinical status and
      devise an effective rehabilitation program in patients with HZ trunk paresis.

PMID- 20159141
TI  - Musculoskeletal sonography in physical and rehabilitation medicine: results of
      the first worldwide survey study.
AB  - OBJECTIVES: To explore the current status of musculoskeletal ultrasound (MSUS) in
      the realm of physical medicine and rehabilitation (PMR), and to determine the
      effects of a 1-day MSUS course on the awareness of physiatrists. DESIGN: Survey.
      SETTING: International Society of Physical and Rehabilitation Medicine Congress,
      2009, Istanbul. PARTICIPANTS: Physiatrists attending the congress (n=276) and the
      MSUS course (n=30). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The
      survey contained 17 multiple-choice and open-ended questions concerning personal
      background, perceptions regarding MSUS, and current use of MSUS. Additionally, a
      group of physicians who attended the 1-day MSUS course before the congress were
      evaluated twice (before and after the course) to assess the change in their
      awareness. RESULTS: Data from 306 physiatrists (with a mean experience of 10.5+/
      8.1 y in the field of PMR) were evaluated. Among the participants, 57.8% were
      using MSUS in their diagnostic algorithms, 90.4% were thinking that physiatrists
      should perform sonography themselves, and 75.1% declared that they would perform
      sonography if they had a device. The ratio of subjects who rated MSUS to be
      essential for their clinical practice increased from 35.7% to 58.6% after the
      MSUS course (P>.05). CONCLUSIONS: Physiatrists strongly believe that they should
      perform MSUS themselves, lack of education and lack of device seem to be
      important issues to be addressed, and even a 1-day course significantly changes
      awareness of MSUS.

PMID- 20159143
TI  - Cortical inhibition, gamma-aminobutyric acid, and major depression: there is
      plenty of smoke but is there fire?

PMID- 20159145
TI  - A phase function to quantify serial dependence between discrete samples.

PMID- 20159144
TI  - Abnormal left and right amygdala-orbitofrontal cortical functional connectivity
      to emotional faces: state versus trait vulnerability markers of depression in
      bipolar disorder.
AB  - BACKGROUND: Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to
      emotional stimuli and relationships with white matter remain little examined in
      bipolar disorder individuals (BD). METHODS: Thirty-one BD (type I; n = 17
      remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy
      individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces
      in two experiments. The FC was computed as linear and nonlinear dependence
      measures between amygdala and OFC time series. Effects of group, laterality, and
      emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter
      fractional anisotropy (FA) relationships were examined. RESULTS: The BD versus HC
      showed significantly greater right amygdala-OFC FC (p < or = .001) in the sad
      experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the
      happy experiment. Depressed but not remitted female BD versus female HC showed
      significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad
      experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p =
      .01). There was a significant nonlinear relationship (p = .001) between left
      amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated
      with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001).
      CONCLUSIONS: In BD, abnormally elevated right amygdala-OFC FC to sad stimuli
      might represent a trait vulnerability for depression, whereas abnormally elevated
      left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to
      intense happy stimuli might represent a depression state marker. Abnormal FC
      measures might normalize with antidepressant medications in BD. Nonlinear
      amygdala-OFC FC-FA relationships in BD and HC require further study.

PMID- 20159146
TI  - Immune response modeling of interferon beta-pretreated influenza virus-infected
      human dendritic cells.
AB  - The pretreatment of human dendritic cells with interferon-beta enhances their
      immune response to influenza virus infection. We measured the expression levels
      of several key players in that response over a period of 13 h both during
      pretreatment and after viral infection. Their activation profiles reflect the
      presence of both negative and positive feedback loops in interferon induction and
      interferon signaling pathway. Based on these measurements, we have developed a
      comprehensive computational model of cellular immune response that elucidates its
      mechanism and its dynamics in interferon-pretreated dendritic cells, and provides
      insights into the effects of duration and strength of pretreatment.

PMID- 20159147
TI  - Drag force as a tool to test the active mechanical response of PC12 neurites.
AB  - We investigate the mechanical response of PC12 neurites subjected to a drag force
      imposed by a laminar flow perpendicular to the neurite axis. The curvature of the
      catenary shape acquired by an initially straight neurite under the action of the
      drag force provides information on both elongation and tension of the neurite.
      This method allows us to measure the rest tension and viscoelastic parameters of
      PC12 neurites and active behavior of neurites. Measurement of oscillations in the
      strain rate of neurites at constant flow rate provides insight on the response of
      molecular motors and additional support for the presence of a negative strain
      rate sensitivity region in the global mechanical response of PC12 neurites.

PMID- 20159148
TI  - An analytic solution of the cable equation predicts frequency preference of a
      passive shunt-end cylindrical cable in response to extracellular oscillating
      electric fields.
AB  - Under physiological and artificial conditions, the dendrites of neurons can be
      exposed to electric fields. Recent experimental studies suggested that the
      membrane resistivity of the distal apical dendrites of cortical and hippocampal
      pyramidal neurons may be significantly lower than that of the proximal dendrites
      and the soma. To understand the behavior of dendrites in time-varying
      extracellular electric fields, we analytically solved cable equations for finite
      cylindrical cables with and without a leak conductance attached to one end by
      employing the Green's function method. The solution for a cable with a leak at
      one end for direct-current step electric fields shows a reversal in polarization
      at the leaky end, as has been previously shown by employing the separation of
      variables method and Fourier series expansion. The solution for a cable with a
      leak at one end for alternating-current electric fields reveals that the leaky
      end shows frequency preference in the response amplitude. Our results predict
      that a passive dendrite with low resistivity at the distal end would show
      frequency preference in response to sinusoidal extracellular local field
      potentials. The Green's function obtained in our study can be used to calculate
      response for any extracellular electric field.

PMID- 20159149
TI  - Strength dependence of cadherin-mediated adhesions.
AB  - Traction forces between adhesive cells play an important role in a number of
      collective cell processes. Intercellular contacts, in particular cadherin-based
      intercellular junctions, are the major means of transmitting force within
      tissues. We investigated the effect of cellular tension on the formation of
      cadherin-cadherin contacts by spreading cells on substrates with tunable
      stiffness coated with N-cadherin homophilic ligands. On the most rigid
      substrates, cells appear well-spread and present cadherin adhesions and
      cytoskeletal organization similar to those classically observed on cadherin
      coated glass substrates. However, when cells are cultured on softer substrates, a
      change in morphology is observed: the cells are less spread, with a more
      disorganized actin network. A quantitative analysis of the cells adhering on the
      cadherin-coated surfaces shows that forces are correlated with the formation of
      cadherin adhesions. The stiffer the substrates, the larger are the average
      traction forces and the more developed are the cadherin adhesions. When cells are
      treated with blebbistatin to inhibit myosin II, the forces decrease and the
      cadherin adhesions disappear. Together, these findings are consistent with a
      mechanosensitive regulation of cadherin-mediated intercellular junctions through
      the cellular contractile machinery.

PMID- 20159150
TI  - Cell adhesion strength is controlled by intermolecular spacing of adhesion
      receptors.
AB  - Spatial patterning of biochemical cues on the micro- and nanometer scale controls
      numerous cellular processes such as spreading, adhesion, migration, and
      proliferation. Using force microscopy we show that the lateral spacing of
      individual integrin receptor-ligand bonds determines the strength of cell
      adhesion. For spacings > or = 90 nm, focal contact formation was inhibited and
      the detachment forces as well as the stiffness of the cell body were
      significantly decreased compared to spacings < or = 50 nm. Analyzing cell
      detachment at the subcellular level revealed that rupture forces of focal
      contacts increase with loading rate as predicted by a theoretical model for
      adhesion clusters. Furthermore, we show that the weak link between the intra- and
      extracellular space is at the intracellular side of a focal contact. Our results
      show that cells can amplify small differences in adhesive cues to large
      differences in cell adhesion strength.

PMID- 20159151
TI  - Mobility of cytoplasmic, membrane, and DNA-binding proteins in Escherichia coli.
AB  - Protein mobility affects most cellular processes, such as the rates of enzymatic
      reactions, signal transduction, and assembly of macromolecular complexes. Despite
      such importance, little systematic information is available about protein
      diffusion inside bacterial cells. Here we combined fluorescence recovery after
      photobleaching with numerical modeling to analyze mobility of a set of
      fluorescent protein fusions in the bacterial cytoplasm, the plasma membrane, and
      in the nucleoid. Estimated diffusion coefficients of cytoplasmic and membrane
      proteins show steep dependence on the size and on the number of transmembrane
      helices, respectively. Protein diffusion in both compartments is thus apparently
      obstructed by a network of obstacles, creating the so-called molecular sieving
      effect. These obstructing networks themselves, however, appear to be dynamic and
      allow a slow and nearly size-independent movement of large proteins and
      complexes. The obtained dependencies of protein mobility on the molecular mass
      and the number of transmembrane helices can be used as a reference to predict
      diffusion rates of proteins in Escherichia coli. Mobility of DNA-binding proteins
      apparently mainly depends on their binding specificity, with FRAP recovery
      kinetics being slower for the highly specific TetR repressor than for the
      relatively nonspecific H-NS regulator.

PMID- 20159152
TI  - The molecular determinants of the increased reduction potential of the rubredoxin
      domain of rubrerythrin relative to rubredoxin.
AB  - Based on the crystal structures, three possible sequence determinants have been
      suggested as the cause of a 285 mV increase in reduction potential of the
      rubredoxin domain of rubrerythrin over rubredoxin by modulating the polar
      environment around the redox site. Here, electrostatic calculations of crystal
      structures of rubredoxin and rubrerythrin and molecular dynamics simulations of
      rubredoxin wild-type and mutants are used to elucidate the contributions to the
      increased reduction potential. Asn(160) and His(179) in rubrerythrin versus
      valines in rubredoxins are predicted to be the major contributors, as the polar
      side chains contribute significantly to the electrostatic potential in the redox
      site region. The mutant simulations show both side chains rotating on a
      nanosecond timescale between two conformations with different electrostatic
      contributions. Reduction also causes a change in the reduction energy that is
      consistent with a linear response due to the interesting mechanism of shifting
      the relative populations of the two conformations. In addition to this, a
      simulation of a triple mutant indicates the side-chain rotations are
      approximately anticorrelated so whereas one is in the high potential
      conformation, the other is in the low potential conformation. However, Ala(176)
      in rubrerythrin versus a leucine in rubredoxin is not predicted to be a large
      contributor, because the solvent accessibility increases only slightly in mutant
      simulations and because it is buried in the interface of the rubrerythrin
      homodimer.

PMID- 20159153
TI  - Bridging timescales and length scales: from macroscopic flux to the molecular
      mechanism of antibiotic diffusion through porins.
AB  - Our aim in this study was to provide an atomic description of ampicillin
      translocation through OmpF, the major outer membrane channel in Escherichia coli
      and main entry point for beta-lactam antibiotics. By applying metadynamics
      simulations, we also obtained the energy barriers along the diffusion pathway. We
      then studied the effect of mutations that affect the charge and size at the
      channel constriction zone, and found that in comparison to the wild-type, much
      lower energy barriers are required for translocation. The expected higher
      translocation rates were confirmed on the macroscopic scale by liposome-swelling
      assays. A microscopic view on the millisecond timescale was obtained by analysis
      of temperature-dependent ion current fluctuations in the presence of ampicillin
      and provide the enthalpic part of the energy barrier. By studying antibiotic
      translocation over various timescales and length scales, we were able to discern
      its molecular mechanism and rate-limiting interactions, and draw biologically
      relevant conclusions that may help in the design of drugs with enhanced
      permeation rates.

PMID- 20159154
TI  - Pardaxin permeabilizes vesicles more efficiently by pore formation than by
      disruption.
AB  - Pardaxin is a 33-amino-acid neurotoxin from the Red Sea Moses sole Pardachirus
      marmoratus, whose mode of action shows remarkable sensitivity to lipid chain
      length and charge, although the effect of pH is unclear. Here we combine optical
      spectroscopy and dye release experiments with laser scanning confocal microscopy
      and natural abundance (13)C solid-state nuclear magnetic resonance to provide a
      more complete picture of how pardaxin interacts with lipids. The kinetics and
      efficiency of release of entrapped calcein is highly sensitive to pH. In vesicles
      containing zwitterionic lipids (PC), release occurs most rapidly at low pH,
      whereas in vesicles containing 20% anionic lipid (PG), release occurs most
      rapidly at high pH. Pardaxin forms stable or transient pores in PC vesicles that
      allow release of contents without loss of vesicle integrity, whereas the
      inclusion of PG promotes total vesicle collapse. In agreement with this, solid
      state nuclear magnetic resonance reveals that pardaxin takes up a trans-membrane
      orientation in 14-O-PC/6-O-PC bicelles, whereas the inclusion of 14-0-PG
      restricts it to contacts with lipid headgroups, promoting membrane lysis. Pore
      formation in zwitterionic vesicles is more efficient than lysis of anionic
      vesicles, suggesting that electrostatic interactions may trap pardaxin in several
      suboptimal interconverting conformations on the membrane surface.

PMID- 20159155
TI  - Partitioning of nonsteroidal antiinflammatory drugs in lipid membranes: a
      molecular dynamics simulation study.
AB  - Using the potential of mean constrained force method, molecular dynamics
      simulations with atomistic details were performed to examine the partitioning and
      nature of interactions of two nonsteroidal antiinflammatory drugs, namely aspirin
      and ibuprofen, in bilayers of dipalmitoylphosphatidylcholine. Two charge states
      (neutral and anionic) of the drugs were simulated to understand the effect of
      protonation or pH on drug partitioning. Both drugs, irrespective of their charge
      state, were found to have high partition coefficients in the lipid bilayer from
      water. However, the values and trends of the free energy change and the location
      of the minima in the bilayer are seen to be influenced by the drug structure and
      charge state. In the context of the transport of the drugs through the bilayer,
      the charged forms were found to permeate fully hydrated in contrast to the
      neutral forms that permeate unhydrated.

PMID- 20159156
TI  - Quantifying biomolecule diffusivity using an optimal Bayesian method.
AB  - We propose a Bayesian method to extract the diffusivity of biomolecules evolving
      freely or inside membrane microdomains. This approach assumes a model of motion
      for the particle considered, namely free Brownian motion or confined diffusion.
      In each framework, a systematic Bayesian scheme is provided for estimating the
      diffusivity. We show that this method reaches the best performances theoretically
      achievable. Its efficiency overcomes that of widely used methods based on the
      analysis of the mean-square displacement. The approach presented here also gives
      direct access to the uncertainty on the estimation of the diffusivity and
      predicts the number of steps of the trajectory necessary to achieve any desired
      precision. Its robustness with respect to noise on the position of the
      biomolecule is also investigated.

PMID- 20159157
TI  - Microarchitecture is severely compromised but motor protein function is preserved
      in dystrophic mdx skeletal muscle.
AB  - Progressive force loss in Duchenne muscular dystrophy is characterized by
      degeneration/regeneration cycles and fibrosis. Disease progression may involve
      structural remodeling of muscle tissue. An effect on molecular motorprotein
      function may also be possible. We used second harmonic generation imaging to
      reveal vastly altered subcellular sarcomere microarchitecture in intact single
      dystrophic mdx muscle cells (approximately 1 year old). Myofibril tilting,
      twisting, and local axis deviations explain at least up to 20% of force drop
      during unsynchronized contractile activation as judged from cosine angle sums of
      myofibril orientations within mdx fibers. In contrast, in vitro motility assays
      showed unaltered sliding velocities of single mdx fiber myosin extracts. Closer
      quantification of the microarchitecture revealed that dystrophic fibers had
      significantly more Y-shaped sarcomere irregularities ("verniers") than wild-type
      fibers (approximately 130/1000 microm(3) vs. approximately 36/1000 microm(3)). In
      transgenic mini-dystrophin-expressing fibers, ultrastructure was restored
      (approximately 38/1000 microm(3) counts). We suggest that in aged dystrophic toe
      muscle, progressive force loss is reflected by a vastly deranged micromorphology
      that prevents a coordinated and aligned contraction. Second harmonic generation
      imaging may soon be available in routine clinical diagnostics, and in this work
      we provide valuable imaging tools to track and quantify ultrastructural worsening
      in Duchenne muscular dystrophy, and to judge the beneficial effects of possible
      drug or gene therapies.

PMID- 20159158
TI  - Material properties of Caenorhabditis elegans swimming at low Reynolds number.
AB  - Undulatory locomotion, as seen in the nematode Caenorhabditis elegans, is a
      common swimming gait of organisms in the low Reynolds number regime, where
      viscous forces are dominant. Although the nematode's motility is expected to be a
      strong function of its material properties, measurements remain scarce. Here, the
      swimming behavior of C. elegans is investigated in experiments and in a simple
      model. Experiments reveal that nematodes swim in a periodic fashion and generate
      traveling waves that decay from head to tail. The model is able to capture the
      experiments' main features and is used to estimate the nematode's Young's modulus
      E and tissue viscosity eta. For wild-type C. elegans, we find E approximately
      3.77 kPa and eta approximately -860 Pa.s; values of eta for live C. elegans are
      negative because the tissue is generating rather than dissipating energy. Results
      show that material properties are sensitive to changes in muscle functional
      properties, and are useful quantitative tools with which to more accurately
      describe new and existing muscle mutants.

PMID- 20159159
TI  - Free energy profile of RNA hairpins: a molecular dynamics simulation study.
AB  - RNA hairpin loops are one of the most abundant secondary structure elements and
      participate in RNA folding and protein-RNA recognition. To characterize the free
      energy surface of RNA hairpin folding at an atomic level, we calculated the
      potential of mean force (PMF) as a function of the end-to-end distance, by using
      umbrella sampling simulations in explicit solvent. Two RNA hairpins containing
      tetraloop cUUCGg and cUUUUg are studied with AMBER ff99 and CHARMM27 force
      fields. Experimentally, the UUCG hairpin is known to be significantly more stable
      than UUUU. In this study, the calculations using AMBER force field give a
      qualitatively correct description for the folding of two RNA hairpins, as the
      calculated PMF confirms the global stability of the folded structures and the
      resulting relative folding free energy is in quantitative agreement with the
      experimental result. The hairpin stabilities are also correctly differentiated by
      the more rapid molecular mechanics-Poisson Boltzmann-surface area approach, but
      the relative free energy estimated from this method is overestimated. The free
      energy profile shows that the native state basin and the unfolded state plateau
      are separated by a wide shoulder region, which samples a variety of native-like
      structures with frayed terminal basepair. The calculated PMF lacks major barriers
      that are expected near the transition regions, and this is attributed to the
      limitation of the 1-D reaction coordinate. The PMF results are compared with
      other studies of small RNA hairpins using kinetics method and coarse grained
      models. The two RNA hairpins described by CHARMM27 are significantly more
      deformable than those represented by AMBER. Compared with the AMBER results, the
      CHARMM27 calculated DeltaG(fold) for the UUUU tetraloop is in better agreement
      with the experimental results. However, the CHARMM27 calculation does not confirm
      the global stability of the experimental UUCG structure; instead, the extended
      conformations are predicted to be thermodynamically stable in solution. This
      finding is further supported by separate unrestrained CHARMM27 simulations, in
      which the UUCG hairpin unfolds spontaneously within 10 ns. The instability of the
      UUCG hairpin originates from the loop region, and propagates to the stem. The
      results of this study provide a molecular picture of RNA hairpin unfolding and
      reveal problems in the force field descriptions for the conformational energy of
      certain RNA hairpin.

PMID- 20159160
TI  - TEM-1 backbone dynamics-insights from combined molecular dynamics and nuclear
      magnetic resonance.
AB  - Dynamic properties of class A beta-lactamase TEM-1 are investigated from
      molecular dynamics (MD) simulations. Comparison of MD-derived order parameters
      with those obtained from model-free analysis of nuclear magnetic resonance (NMR)
      relaxation data shows high agreement for N-H moieties within alpha- and beta
      secondary structures, but significant deviation for those in loops. This was
      expected, because motions slower than the protein global tumbling often take
      place in loop regions. As previously shown using NMR, TEM-1 is a highly ordered
      protein. Motions are observed within the Omega loop that could, upon substrate
      binding, stabilize E166 in a catalytically efficient position as the cavity
      between the protein core and the Omega loop is partially filled. The rigidity of
      active site residues is consistent with the enzyme high turnover number. MD data
      are also shown to be useful during the model selection step of model-free
      analysis: local N-H motions observed over the course of the trajectories help
      assess whether a peptide plan undergoes low or high amplitude motions on one or
      more timescales. This joint use of MD and NMR provides a better description of
      protein dynamics than would be possible using either technique alone.

PMID- 20159161
TI  - (Un)Folding mechanisms of the FBP28 WW domain in explicit solvent revealed by
      multiple rare event simulation methods.
AB  - We report a numerical study of the (un)folding routes of the truncated FBP28 WW
      domain at ambient conditions using a combination of four advanced rare event
      molecular simulation techniques. We explore the free energy landscape of the
      native state, the unfolded state, and possible intermediates, with replica
      exchange molecular dynamics. Subsequent application of bias-exchange metadynamics
      yields three tentative unfolding pathways at room temperature. Using these paths
      to initiate a transition path sampling simulation reveals the existence of two
      major folding routes, differing in the formation order of the two main hairpins,
      and in hydrophobic side-chain interactions. Having established that the hairpin
      strand separation distances can act as reasonable reaction coordinates, we employ
      metadynamics to compute the unfolding barriers and find that the barrier with the
      lowest free energy corresponds with the most likely pathway found by transition
      path sampling. The unfolding barrier at 300 K is approximately 17 k(B)T
      approximately 42 kJ/mol, in agreement with the experimental unfolding rate
      constant. This work shows that combining several powerful simulation techniques
      provides a more complete understanding of the kinetic mechanism of protein
      folding.

PMID- 20159162
TI  - Exploring the contribution of collective motions to the dynamics of forced
      unfolding in tubulin.
AB  - Decomposition of the intrinsic dynamics of proteins into collective motions among
      distant regions of the protein structure provides a physically appealing approach
      that couples the dynamics of the system with its functional role. The cellular
      functions of microtubules (an essential component of the cytoskeleton in all
      eukaryotic cells) depend on their dynamic instability, which is altered by
      various factors among which applied forces are central. To shed light on the
      coupling between forces and the dynamic instability of microtubules, we focus on
      the investigation of the response of the microtubule subunits (tubulin) to
      applied forces. We address this point by adapting an approach designed to survey
      correlations for the equilibrium dynamics of proteins to the case of correlations
      for proteins forced-dynamics. The resulting collective motions in tubulin have a
      number of functional implications, such as the identification of long-range
      couplings with a role in blocking the dynamic instability of microtubules. A
      fundamental implication of our study for the life of a cell is that, to increase
      the likelihood of unraveling of large cytoskeletal filaments under physiological
      forces, molecular motors must use a combination of pulling and torsion rather
      than just pulling.

PMID- 20159163
TI  - Thermo- and mesostabilizing protein interactions identified by temperature
      dependent statistical potentials.
AB  - The goal of controlling protein thermostability is tackled here through
      establishing, by in silico analyses, the relative weight of residue-residue
      interactions in proteins as a function of temperature. We have designed for that
      purpose a (melting-) temperature-dependent, statistical distance potential, where
      the interresidue distances are computed between the side-chain geometric centers
      or their functional centers. Their separate derivation from proteins of either
      high or low thermal resistance reveals the interactions that contribute most to
      stability in different temperature ranges. Thermostabilizing interactions include
      salt bridges and cation-pi interactions (especially those involving arginine),
      aromatic interactions, and H-bonds between negatively charged and some aromatic
      residues. In contrast, H-bonds between two polar noncharged residues or between a
      polar noncharged residue and a negatively charged residue are relatively less
      stabilizing at high temperatures. An important observation is that it is
      necessary to consider both repulsive and attractive interactions in overall
      thermostabilization, as the degree of repulsion may also vary with temperature.
      These temperature-dependent potentials are not only useful for the identification
      of meso- and thermostabilizing pair interactions, but also exhibit predictive
      power, as illustrated by their ability to predict the melting temperature of a
      protein based on the melting temperature of homologous proteins.

PMID- 20159164
TI  - Nonlocal interactions are responsible for tertiary structure formation in
      staphylococcal nuclease.
AB  - Rapid molecular collapse mediated by nonlocal interactions is believed to be a
      crucial event for protein folding. To investigate the role of nonlocal
      interactions in tertiary structure formation, we performed a nonlocal interaction
      substitution mutation analysis on staphylococcal nuclease (SNase). Y54 and I139
      of wild-type (WT) SNase and Delta140-149 were substituted by cysteine to form
      intramolecular disulfide bonds, respectively called WT-SS and Delta140-149-SS.
      Under physiological conditions, the reduced form of Delta140-149-SS appears to
      assume a denatured structure; in contrast, the oxidized form of Delta140-149-SS
      forms a native-like structure. From this result, we conclude that the C-terminal
      region participates in a nonlocal interaction that is indispensable for the
      native structure. Although the oxidized form of WT-SS assumes a more compact
      denatured structure under acidic conditions than the WT, the kinetic measurements
      reveal that the refolding reactions of both the reduced and oxidized forms of WT
      SS are similar to those of the WT, suggesting that an intact nonlocal interaction
      is established within the dead time (22 ms). On the basis of these results, we
      propose that the native nonlocal contact established at the early stage of the
      folding process facilitates further secondary structure formation.

PMID- 20159165
TI  - Primary changes of the mechanical properties of Southern Bean Mosaic Virus upon
      calcium removal.
AB  - The mechanical properties of viral shells are crucial determinates for the
      pathway and mechanism by which the genetic material leaves the capsid during
      infection and have therefore been studied by atomic force microscopy as well as
      by atomistic simulations. The mechanical response to forces from inside the
      capsid are found to be relevant, especially after ion removal from the shell
      structure, which is generally assumed to be essential during viral infection;
      however, atomic force microscopy measurements are restricted to probing the
      capsids from outside, and the primary effect of ion removal is still
      inaccessible. To bridge this gap, we performed atomistic force-probe molecular
      dynamics simulations of the complete solvated icosahedral shell of Southern Bean
      Mosaic Virus and compared the distribution of elastic constants and yielding
      forces on the icosahedral shell for probing from inside with the distribution of
      outside mechanical properties obtained previously. Further, the primary effect of
      calcium removal on the mechanical properties on both sides, as well as on their
      spatial distribution, is quantified. Marked differences are seen particularly at
      the pentamer centers, although only small structural changes occur on the short
      timescales of the simulation. This unexpected primary effect, hence, precedes
      subsequent effects due to capsid swelling. In particular, assuming that genome
      release is preceded by an opening of capsomers instead of a complete capsid
      bursting, our observed weakening along the fivefold symmetry axes let us suggest
      pentamers as possible exit ports for RNA release.

PMID- 20159166
TI  - Distinguishing between protein dynamics and dye photophysics in single-molecule
      FRET experiments.
AB  - Forster resonance energy transfer (FRET) efficiency distributions in single
      molecule experiments contain both structural and dynamical information.
      Extraction of this information from these distributions requires a careful
      analysis of contributions from dye photophysics. To investigate how mechanisms
      other than FRET affect the distributions obtained by counting donor and acceptor
      photons, we have measured single-molecule fluorescence trajectories of a small
      alpha/beta protein, i.e., protein GB1, undergoing two-state, folding/unfolding
      transitions. Alexa 488 donor and Alexa 594 acceptor dyes were attached to
      cysteines at positions 10 and 57 to yield two isomers-donor(10)/acceptor(57) and
      donor(57)/acceptor(10)-which could not be separated in the purification. The
      protein was immobilized via binding of a histidine tag added to a linker sequence
      at the N-terminus to cupric ions embedded in a polyethylene-glycol-coated glass
      surface. The distribution of FRET efficiencies assembled from the trajectories is
      complex with widths for the individual peaks in large excess of that caused by
      shot noise. Most of this complexity can be explained by two interfering
      photophysical effects-a photoinduced red shift of the donor dye and differences
      in the quantum yield of the acceptor dye for the two isomers resulting from
      differences in quenching rate by the cupric ion. Measurements of steady-state
      polarization, calculation of the donor-acceptor cross-correlation function from
      photon trajectories, and comparison of the single molecule and ensemble kinetics
      all indicate that conformational distributions and dynamics do not contribute to
      the complexity.

PMID- 20159167
TI  - Susceptibility of different proteins to flow-induced conformational changes
      monitored with Raman spectroscopy.
AB  - By directly monitoring stirred protein solutions with Raman spectroscopy, the
      reversible unfolding of proteins caused by fluid shear is examined for several
      natural proteins with varying structural properties and molecular weight. While
      complete denaturation is not observed, a wide range of spectral variances occur
      for the different proteins, indicating subtle conformational changes that appear
      to be protein-specific. A number of significant overall trends are apparent from
      the study. For globular proteins, the overall extent of spectral variance
      increases with protein size and the proportion of beta-structure. For two less
      structured proteins, fetuin and alpha-casein, the observed changes are of
      relatively low magnitude, despite the greater molecular structural mobility of
      these proteins. This implies that other protein-specific factors, such as
      posttranslational modifications, may also be significant. Individual band changes
      occurring in the spectral profiles of each individual protein are also discussed
      in detail.

PMID- 20159168
TI  - Expanding two-photon intravital microscopy to the infrared by means of optical
      parametric oscillator.
AB  - Chronic inflammation in various organs, such as the brain, implies that different
      subpopulations of immune cells interact with the cells of the target organ. To
      monitor this cellular communication both morphologically and functionally, the
      ability to visualize more than two colors in deep tissue is indispensable. Here,
      we demonstrate the pronounced power of optical parametric oscillator (OPO)-based
      two-photon laser scanning microscopy for dynamic intravital imaging in hardly
      accessible organs of the central nervous and of the immune system, with
      particular relevance for long-term investigations of pathological mechanisms
      (e.g., chronic neuroinflammation) necessitating the use of fluorescent proteins.
      Expanding the wavelength excitation farther to the infrared overcomes the current
      limitations of standard Titanium:Sapphire laser excitation, leading to 1),
      simultaneous imaging of fluorophores with largely different excitation and
      emission spectra (e.g., GFP-derivatives and RFP-derivatives); and 2), higher
      penetration depths in tissue (up to 80%) at higher resolution and with reduced
      photobleaching and phototoxicity. This tool opens up new opportunities for deep
      tissue imaging and will have a tremendous impact on the choice of protein
      fluorophores for intravital applications in bioscience and biomedicine, as we
      demonstrate in this work.

PMID- 20159169
TI  - Nanogap dielectric spectroscopy for aptamer-based protein detection.
AB  - Among the various label-free methods for monitoring biomolecular interactions,
      capacitive sensors stand out due to their simple instrumentation and
      compatibility with multiplex formats. However, electrode polarization due to ion
      gradient formation and noise from solution conductance limited early dielectric
      spectroscopic measurements to high frequencies only, which in turn limited their
      sensitivity to biomolecular interactions, as the applied excitation signals were
      too fast for the charged macromolecules to respond. To minimize electrode
      polarization effects, capacitive sensors with 20 nm electrode separation were
      fabricated using silicon dioxide sacrificial layer techniques. The nanoscale
      separation of the capacitive electrodes in the sensor results in an enhanced
      overlapping of electrical double layers, and apparently a more ordered "ice-like"
      water structure. Such effects in turn reduce low frequency contributions from
      bulk sample resistance and from electrode polarization, and thus markedly enhance
      sensitivity toward biomolecular interactions. Using these nanogap capacitive
      sensors, highly sensitive, label-free aptamer-based detection of protein
      molecules is achieved.

PMID- 20159171
TI  - Multipurpose prevention technologies for sexual and reproductive health: gaining
      momentum and promise.

PMID- 20159170
TI  - Equilibrium sampling for biomolecules under mechanical tension.
AB  - In the studies of force-induced conformational transitions of biomolecules, the
      large timescale difference from experiments presents the challenge of obtaining
      convergent sampling for molecular dynamics simulations. To circumvent this
      fundamental problem, an approach combining the replica-exchange method and
      umbrella sampling (REM-US) was developed to simulate mechanical stretching of
      biomolecules under equilibrium conditions. Equilibrium properties of
      conformational transitions can be obtained directly from simulations without
      further assumptions. To test the performance, we carried out REM-US simulations
      of atomic force microscope (AFM) stretching and relaxing measurements on the
      polysaccharide pustulan, a (1-->6)-beta-D-glucan, which undergoes well
      characterized rotameric transitions in the backbone bonds. With significantly
      enhanced sampling convergence and efficiency, the REM-US approach closely
      reproduced the equilibrium force-extension curves measured in AFM experiments.
      Consistent with the reversibility in the AFM measurements, the new approach
      generated identical force-extension curves in both stretching and relaxing
      simulations-an outcome not reported in previous studies, proving that equilibrium
      conditions were achieved in the simulations. REM-US may provide a robust approach
      to modeling of mechanical stretching on polysaccharides and even nucleic acids.

PMID- 20159172
TI  - Community-based health workers can safely and effectively administer injectable
      contraceptives: conclusions from a technical consultation.

PMID- 20159173
TI  - Nonsteroidal anti-inflammatory drugs and hormonal contraceptives for pain relief
      from dysmenorrhea: a review.
AB  - BACKGROUND: This article is a comprehensive overview of dysmenorrhea and a
      systematic review of the available literature on the use of nonsteroidal anti
      inflammatory drugs (NSAIDs) and hormonal contraceptives for the therapy and
      management of dysmenorrhea. STUDY DESIGN: A comprehensive search of the PubMed
      database for clinical trials and observational studies of dysmenorrhea treatments
      from 2004 onwards. RESULTS: Eighteen publications were identified. Ten randomized
      controlled trials (RCTs) assessing NSAIDs for treating primary dysmenorrhea
      demonstrated superior pain relief compared with placebo, but no superiority was
      established among different NSAIDS. Two RCTs and six nonrandomized observational
      or prospective studies assessing the effect of hormonal contraceptives on
      dysmenorrhea strongly suggest a beneficial effect for dysmenorrheic pain relief
      and were conducted mainly in larger populations (N=41-6169) than those in the
      NSAID trials (N=10-337). Ethinylestradiol/chlormadinone acetate was the only
      formulation that provided a more pronounced relief of dysmenorrheic pain compared
      with a parallel alternative or previously used hormonal contraceptive.
      Methodological inconsistencies were widespread between the hormonal contraceptive
      studies. CONCLUSIONS: The findings of this review support the use of NSAIDs as a
      first-line therapy for pain relief from dysmenorrhea in women without wish for
      contraception. For women who wish contraception, combined oral contraceptives
      (COCs) are the preferential therapy for pain relief from dysmenorrhea as the
      additional noncontraceptive benefit of pain relief from dysmenorrhea is not
      linked to additional risks, eliminates the risks associated with taking NSAIDs
      and is a more suitable long-term option. Recommendations are made to strengthen
      the impact of future trials through improved methodology.

PMID- 20159175
TI  - Epidemiological and clinical aspects of migraine in users of combined oral
      contraceptives.
AB  - BACKGROUND: Migraine was assessed in users of combined oral contraceptives
      (COCs). STUDY DESIGN: This study had a cross-sectional design. Women with
      headaches were evaluated according to International Headache Society criteria and
      subsequently allocated to a "migraine" or "non-migraine" group. RESULTS: Migraine
      was detected in 80/480 women (16.6%), while other types of headache not
      classified as migraine were observed in 400 women (83.4%). Following COC use,
      headaches worsened in 32.5% and 19.3% [odds ratio (OR)=3.02; 95% confidence
      interval (CI)=1.68-5.4] and improved in 30% and 13.8% (OR=3.9; 95% CI=2.12-7.18)
      of the "migraine" and "non-migraine" groups, respectively. In the migraine group
      only, headache episodes occurred predominantly during or around the hormone-free
      interval (OR=2.05; 95% CI=1.26-3.35). The combination of ethinylestradiol (EE)
      and drospirenone (DRS) was significantly associated with an improvement in the
      frequency and/or intensity of migraine-type headaches, compared with other types
      of COCs. CONCLUSIONS: The prevalence of migraine in COC users appears similar to
      that found in the general population. Migraines, but not other types of headache,
      were significantly affected by COCs. The EE/DRS combination was associated with a
      greater likelihood of improvement in migraine compared with other types of COCs.

PMID- 20159174
TI  - Sino-implant (II)--a levonorgestrel-releasing two-rod implant: systematic review
      of the randomized controlled trials.
AB  - BACKGROUND: Sino-implant (II) is a subdermal contraceptive implant manufactured
      in China. This two-rod levonorgestrel-releasing implant has the same amount of
      active ingredient (150 mg levonorgestrel) and mechanism of action as the widely
      available contraceptive implant Jadelle. We examined randomized controlled trials
      of Sino-implant (II) for effectiveness and side effects. STUDY DESIGN: We
      searched electronic databases for studies of Sino-implant (II) and then
      restricted our review to randomized controlled trials. The primary outcome of
      this review was pregnancy. RESULTS: Four randomized trials with a total of 15,943
      women assigned to Sino-implant (II) had first-year probabilities of pregnancy
      ranging from 0.0% to 0.1%. Cumulative probabilities of pregnancy during the 4
      years of the product's approved duration of use were 0.9% and 1.06% in the two
      trials that presented date for 4-year use. Five-year cumulative probabilities of
      pregnancy ranged from 0.7% to 2.1%. In one trial, the cumulative probability of
      pregnancy more than doubled during the fifth year (from 0.9% to 2.1%), which may
      be why the implant is approved for 4 years of use in China. Five-year cumulative
      probabilities of discontinuation due to menstrual problems ranged from 12.5% to
      15.5% for Sino-implant (II). CONCLUSIONS: Sino-implant (II) is one of the most
      effective contraceptives available today. These available clinical data, combined
      with independent laboratory testing, and the knowledge that 7 million women have
      used this method since 1994, support the safety and effectiveness of Sino-implant
      (II). The lower cost of Sino-implant (II) compared with other subdermal implants
      could improve access to implants in resource-constrained settings.

PMID- 20159176
TI  - Effects of the contraceptive patch and the vaginal ring on bone metabolism and
      bone mineral density: a prospective, controlled, randomized study.
AB  - BACKGROUND: This study was conducted to compare the effects of the combined
      contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg
      of etonorgestrel daily with the effects of the contraceptive patch, a transdermal
      system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin
      on bone turnover and bone mineral density (BMD) in young fertile women. STUDY
      DESIGN: On the basis of a randomized, computer-generated list, 40 women desiring
      contraception were assigned to a 12-month treatment with a patch delivering a
      daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra, Janssen-Cilag,
      Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a
      daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing, Organon,
      Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as
      healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary
      calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD)
      levels were measured. At baseline and after 12 months, lumbar BMD was determined
      by dual-energy X-ray absorptiometry. RESULTS: In Groups A and B, urinary PYD and
      D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal
      values and Group C values (p<.05). In Groups A and B, serum calcium levels were
      significantly increased after 6 months. No significant difference was detected
      between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels
      and in osteocalcin levels. At 12 months, no significant difference was detected
      in spinal BMD values between the three groups and in comparison with basal
      values. CONCLUSION: Both contraceptive systems exert a similar positive influence
      on bone turnover in young postadolescent women.

PMID- 20159177
TI  - Bleeding patterns and menstrual-related symptoms with the continuous use of a
      contraceptive combination of ethinylestradiol and drospirenone: a randomized
      study.
AB  - BACKGROUND: The objective of this study was to compare bleeding patterns of women
      using a contraceptive combination of 30 mcg ethinylestradiol (EE) and 3 mg
      drospirenone (DRSP) continuously or cyclically. Menstrual-related symptoms were
      also evaluated. STUDY DESIGN: This open, prospective, randomized study evaluated
      78 women using the EE/DRSP combination continuously for 168 days or for six 28
      day cycles, each followed by a 7-day hormone-free interval. A diary with pre
      established scales was used to assess the frequency and intensity of bleeding and
      menstrual-related symptoms. RESULTS: Amenorrhea increased with continuous use;
      62.2% of women with continuous use were amenorrheic at the end of treatment (95%
      CI: 46.6-77.8%). Dysmenorrhea, headache, acne, nausea, edema and increased
      appetite improved significantly in the continuous-use group, and mastalgia and
      edema in the cyclic-use group (p<.05). Six subjects in the continuous-use group
      (15.4%) and three in the cyclic-use group (7.7%) discontinued due to adverse
      events. CONCLUSIONS: Continuous use was associated with amenorrhea and fewer
      menstrual-related symptoms compared to cyclic use.

PMID- 20159178
TI  - Extended regimens of the contraceptive vaginal ring: evaluation of clinical
      aspects.
AB  - BACKGROUND: Oral contraceptives used for extended periods of time have been
      extensively studied because of their potential benefits; however, there have been
      few publications on extended regimens of vaginal contraceptive rings. The aim of
      this study was to evaluate the clinical symptoms, body weight and blood pressure
      changes in women using the vaginal ring continuously over a 1-year period. STUDY
      DESIGN: This prospective cohort evaluated clinical aspects (dysmenorrhea,
      headache, breast tenderness, leg pain and irritability), body weight and blood
      pressure changes in 75 women (18-37 years of age) using a vaginal ring releasing
      120 mcg of etonogestrel and 15 mcg of ethinyl estradiol daily, over a continuous
      period of 84 days, followed by a 7-day ring-free interval, during 1 year. The chi
      square, Wilcoxon and paired t tests were used to analyze differences in the
      outcomes of interest. RESULTS: Compared to pre-enrollment status, at the end of
      the study period, the patients reported significantly less dysmenorrhea and
      irritability, a nonsignificant decrease in breast tenderness, leg pain and
      headaches. Blood pressure measurements remained unchanged. Although weight and
      body mass index increased significantly among users, they remained within the
      expected biological variation range. CONCLUSION: The vaginal ring used on an
      extended regimen is a well-tolerated contraceptive method and also offers
      noncontraceptive benefits.

PMID- 20159179
TI  - A randomized prospective trial comparing the levonorgestrel-releasing
      intrauterine system with thermal balloon ablation for the treatment of heavy
      menstrual bleeding.
AB  - BACKGROUND: Use of the levonorgestrel-releasing intrauterine system (LNG-IUS) was
      compared with thermal balloon ablation (TBA) for the treatment of heavy menstrual
      bleeding (HMB). STUDY DESIGN: A prospective randomized trial comparing the LNG
      IUS (n=30 women) and TBA (n=28 women). RESULTS: Hemoglobin levels increased
      (p<.001) and blood loss was reduced (p<.001) in both groups after 1 year of
      treatment. Menstrual bleeding was less in the LNG-IUS group compared to the TBA
      group at 6 and 12 months of treatment (p=.035 and p=.048, respectively).
      Intermenstrual bleeding was significantly less in the TBA group at 6 months
      compared to the LNG-IUS group (p=.044); however, there was no significant
      difference at 12 months (p=.129). No difference was found in psychological
      aspects between pre- and posttreatment variables in either of the groups
      (p=.537). CONCLUSIONS: Both the LNG-IUS and TBA appear to be effective in
      controlling HMB; however, posttreatment uterine bleeding patterns are different.

PMID- 20159180
TI  - Results of a safety and feasibility study of the diaphragm used with ACIDFORM Gel
      or K-Y Jelly.
AB  - BACKGROUND: New strategies are needed for preventing HIV infection in women. One
      potential approach is female-initiated use of an effective topical microbicidal
      gel in combination with a cervical barrier such as the diaphragm. STUDY DESIGN:
      Randomized, placebo-controlled safety and feasibility trial of diaphragm with
      vaginal gel during 6 months of use among 120 HIV-negative sexually active women
      in Johannesburg, South Africa. RESULTS: Pelvic event rates were 338.3 and 247.1
      per 100 women-years in the ACIDFORM gel (plus diaphragm) and K-Y(R) Jelly (plus
      diaphragm) groups, respectively, with a rate ratio of 1.37 (95% CI: 0.89-2.11).
      Most women found diaphragm with gel use acceptable. CONCLUSION: There was a trend
      towards more safety events in the ACIDFORM plus diaphragm group, although no
      primary comparisons achieved statistical significance. Adding an effective
      microbicidal gel to a mechanical barrier may still prove to be an important and
      acceptable combination method to help prevent pregnancy and HIV/sexually
      transmitted infection transmission.

PMID- 20159181
TI  - A comparison of transabdominal and transvaginal ultrasonography for determination
      of gestational age and clinical outcomes in women undergoing early medical
      abortion.
AB  - BACKGROUND: We sought to establish the accuracy of abdominal ultrasonography in
      determining gestational age and identifying the presence of a gestational sac and
      embryonic pole before and after medical abortion. METHODS: We included all 120
      women enrolled in a study of simultaneous oral mifepristone and buccal
      misoprostol for abortion through 63 days' gestation. Vaginal and abdominal
      ultrasound examinations were performed before and 24 h after medication
      administration. Visualization of a gestational sac and embryonic pole and
      presence or absence of cardiac activity were recorded. Sensitivity and
      specificity were calculated with the results from vaginal ultrasonography as the
      gold standard. The effect of body mass index (BMI) on ultrasound findings was
      also assessed. RESULTS: Before treatment, the sensitivities of abdominal
      ultrasonography were 100% (95% CI 97-100) and 68% (95% CI 58-77) for presence of
      a gestational sac and an embryonic pole, respectively. Overall, abdominal imaging
      underestimated mean gestational age by 1.6 days (95% CI 1.0-2.2). After
      treatment, abdominal ultrasonography missed three of 34 retained gestational sacs
      (sensitivity 91%, 95% CI 76-98%). Fourteen women had gestational cardiac activity
      by vaginal ultrasound at follow-up. Abdominal imaging identified the gestational
      sac in all cases, but cardiac motion was only visible in 10 (71%, 95% CI 42-92%).
      For every 10-point increase in BMI, the odds ratio for missing an embryonic pole
      at baseline was 2.8 (95% CI 1.5-5.0). CONCLUSIONS: Abdominal ultrasonography is
      sensitive for diagnosing the presence or absence of a gestational sac, but less
      sensitive at detecting an embryonic pole. This may lead to a small
      underestimation of gestational age and missing a continuing pregnancy at follow
      up when one exists.

PMID- 20159182
TI  - Antimullerian hormone and obesity: insights in oral contraceptive users.
AB  - BACKGROUND: The study was conducted to examine the impact of oral contraceptives
      (OCs) on serum antimullerian hormone (AMH) levels by obesity status in
      reproductive-age women. STUDY DESIGN: Ovulatory women, ages 18-35 years, of
      normal (<25 kg/m(2); n=10) and obese (>30 kg/m(2); n=10) body mass index (BMI)
      received a low-dose OC (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for two
      cycles. Serum samples obtained at several time points during active pill use and
      hormone-free intervals were analyzed for AMH, follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), estradiol and inhibin B. RESULTS: AMH levels did not
      differ by OC cycle day in either BMI group. On average, AMH levels were 34% lower
      in the obese group (2.9+/-2.1 vs. 4.4+/-1.8 ng/mL, p<.05). Modeling to determine
      differences in AMH throughout the cycle based on obesity status demonstrated
      significantly lower levels (p<.05), whereas serum AMH, FSH, LH, estradiol and
      inhibin B levels revealed no correlations when all time points were included.
      CONCLUSIONS: In reproductive-age women, serum AMH levels do not appear to
      fluctuate during OC use, but AMH levels are significantly lower in obese women.
      Lower levels do not appear to be due to differences in gonadotropin levels or
      ovarian activity.

PMID- 20159183
TI  - Perceived competence and contraceptive use during adolescence.
AB  - BACKGROUND: Little is known about psychosocial correlates of different
      contraceptive methods in adolescence. STUDY DESIGN: Cross-sectional analyses of
      209 postmenarcheal girls [mean age (years)+/-SD=15.68+/-1.74], primarily
      Caucasian (62.8%) or African American (32.8%). Competence (activities and social)
      and rule-breaking behavior were assessed by the Youth Self Report (YSR;
      adolescent) and the Child Behavior Checklist (CBCL; parent). Three contraceptive
      use groups were created: no hormonal contraceptive (n=142), combined oral
      contraceptives or the transdermal patch (COCs/patch, n=41), and depot
      medroxyprogesterone acetate (DMPA, n=20). RESULTS: There was a significant effect
      of contraceptive-use group on competence (p=.003). The DMPA group had lower
      competence (CBCL activities and social; YSR social) than the no-hormonal
      contraceptive and COCs/patch groups. The COCs/patch group scored lower than the
      no-hormonal-contraceptive group on YSR activities competence, but was not
      different from the DMPA group. Lastly, there was an effect of contraceptive-use
      group on CBCL (but not YSR) rule-breaking behavior (p=.029) with the DMPA group
      having higher rule-breaking behavior than the other groups. CONCLUSIONS: Type of
      contraceptive method was associated with parent and adolescent's perceived
      competence. For rule-breaking behavior, parental perception may be more relevant
      to contraceptive use.

PMID- 20159184
TI  - Perceptions of the safety of oral contraceptives among a predominantly Latina
      population in Texas.
AB  - BACKGROUND: Fear of side effects and previous negative experiences are common
      reasons for contraceptive nonuse. STUDY DESIGN: We collected information about
      perceptions of oral contraceptive (OC) safety from 1271 women 18-49 years old in
      El Paso, TX, and compared their responses to a medical evaluation by a nurse
      practitioner. We also asked participants about their interest in obtaining OCs
      over the counter (OTC). RESULTS: Among 794 women potentially at risk of
      unintended pregnancy, 56.0% said that OCs were medically safe for them. Reasons
      given for OCs being unsafe were related to fears of side effects and prior
      negative experiences rather than true contraindications. Older women and
      participants recruited at the less affluent recruitment site were significantly
      more likely to report that OCs were medically unsafe for them (p<.05). Nonusers
      who thought OCs were medically unsafe for them were as likely to be medically
      eligible for use as current hormonal users. Among nonusers or nonhormonal users
      and potential OC candidates (n=601), 60.2% said they would be more likely to use
      OCs if they were available OTC. CONCLUSIONS: Women's perception of OC safety does
      not correlate well with medical eligibility for use. More education about the
      safety and health benefits of hormonal contraception is needed. OTC availability
      might contribute to more positive safety perceptions of OCs compared to a
      prescription environment.

PMID- 20159185
TI  - In vitro Actinomyces israelii biofilm development on IUD copper surfaces.
AB  - BACKGROUND: Female pelvic actinomycosis may involve fallopian tubes, ovaries,
      uterus and bladder. This condition is often associated with the use of
      intrauterine contraceptive devices (IUDs), vaginal pessaries and/or tampons. The
      predominant causative agent of human actinomycosis is Actinomyces israelii, which
      has been found on copper IUDs retrieved from patients. STUDY DESIGN: In this
      work, a biofilm of A. israelii was developed in vitro on copper surfaces immersed
      in a simulated uterine fluid under anaerobic conditions. The biofilm was
      characterized using scanning electron microscopy (SEM), energy dispersive X-ray
      and atomic force microscopy. RESULTS: The capacity of A. israelii to develop a
      biofilm over copper surfaces in synthetic media was demonstrated. SEM
      micrographies illustrate the exopolysaccharides production and bacterial
      distribution. CONCLUSION: A. israelii was able to attach and grow in synthetic
      intrauterine media and to present on the copper surface is likely due to the
      production of biofilm.

PMID- 20159186
TI  - Is there evidence for tripling the dose of 200 mg mifepristone for medical
      abortion?

PMID- 20159189
TI  - Care of the pediatric cardiac surgery patient--part 1.

PMID- 20159190
TI  - [Antidepressant treatment and suicide risk].

PMID- 20159191
TI  - [Assessment of the outcome of anorexia nervosa: construction of a self
      administered questionnaire based on the patients' perception].
AB  - INTRODUCTION: Our working hypothesis is that a better insight into the outcome of
      patients suffering from anorexia nervosa should contribute to preventing relapses
      and further complications and assessing treatment efficiency. Through anorexia
      nervosa, the patients express the difficulty they have to view themselves as
      specific subjects. OBJECTIVE: The current classic outcome evaluation is based on
      the study of objective events, which only partially reflect the reality of the
      patients' outcome at a subjective level. The objective of this study was to set
      up a new assessing instrument of the outcome of patients suffering from anorexia
      nervosa, essentially based on the patients' perception of their experience.
      METHOD: The methodology used has been based on: (1) the conduct by the main
      investigator of unstructured interviews using "free association", with the help
      of an interview guide. The anorexia nervosa patients were recruited among those
      who were hospitalized on an isolation contract, or among outpatients under a
      psychiatrist/psychoanalyst's supervision, aged over 25 years old so that they may
      have started their reproductive life. The study included 30 patients; (2) the
      analysis of the interview contents backed by preexisting hypotheses and by new
      ones suggested by the expression of the patients' perception, so as to set up an
      inventory of new themes; (3) the construction of a self-administered
      questionnaire starting from the development of each theme into several questions
      taking up the patients' own words and offering 4 possible answers (disagree
      completely, disagree, agree, quite agree). RESULTS: The analysis of the
      interviews contents has led to the development of 11 themes. The self
      administered questionnaire includes a total of 124 items stemming from the
      development of each theme into between 9 and 16 items that were mixed in the
      version submitted to patients. DISCUSSION: This original interpretation of the
      outcome of the patients through their experience provides a better understanding
      of their relation to desire and pleasure, and consequently of the evolution of
      their subjectivity. By integrating several aspects of the disease expression, our
      instrument constitutes an alternative to the combination of several non-specific
      tools in anorexia nervosa. It thus avoids the atomization of the pathology and
      respects the specificity of its structure. The analysis of the disease function
      in the emergence of their subjectivity rather than the static observation of its
      symptoms has led to the development of new themes. CONCLUSION: The validation of
      this new methodological approach of the follow-up of anorexia nervosa based on
      the patients' perception of the evolution of their disease, aside from
      anthropometrical or physiological parameters, will have to be tested on a new
      population of patients. A quantitative score will be developed in association
      with the self-administered questionnaire. Its use in further epidemiological
      studies will enable a scientific assessment of the patients' outcome, and better
      prevent further complications and relapses, by screening patients with a
      pejorative risk. The ultimate aim is to improve these patients' care.

PMID- 20159192
TI  - [Creation of a body satisfaction and global self-perception questionnaire: the
      QSCPGS. Norms and first validation].
AB  - INTRODUCTION: A review of the literature finds that everything concerning the
      body is a source of self-questioning. However, if a feeling of comfort or of
      discomfort is perceived within the body, it is difficult to quantify and to
      define this perception. This is because this feeling is multifactorial and
      characterized by behaviors and symptoms that are not explicit. METHOD: To resolve
      this perception, we created a self-reported questionnaire allowing for the
      estimation of "body satisfaction and global self-perception". RESULTS: We present
      here the normative values collected with 788 subjects: 541 "non clinical"
      subjects and 247 "clinical subjects" consisting of inpatients hospitalized for
      major depressive disorder. In the "non clinical" group, the results show a good
      stability of scores. However, the female participants of this group have values
      (39.1) significantly (p<0.03) lower than the male participants (44.8). The
      evolution according to age showed a peak in physical satisfaction and of global
      self-perception between the age of 30 and 50. The score of this QSCPGS is very
      significantly (p<0.0001) higher in the "non clinical" group (43) than in the
      "clinical group" (-2); this confirms the good validity of the criterion. Finally,
      the average gains in the total score of the QSCPGS after a relaxation session
      with 34 depressed subjects are 23.7 (-12.2 before and 11.5 after). DISCUSSION:
      This very significant advantage indicates that this questionnaire is sensitive to
      changes connected with a therapeutic intervention. The QSCPGS can thus be useful
      for the evaluation of body satisfaction or dissatisfaction as well as the mood
      associated with it; thus, it permits one to clarify the concept of well-being
      within "non clinical subjects" and to record the modifications provided by
      therapy, both at a physical level and a level of global self-perception. Future
      studies must now be submitted in different study groups such as: diverse
      pathologies, high level sportsmen, (etc.), this will allow us to gather
      information that will help establish specific therapies or effective preventative
      measures.

PMID- 20159193
TI  - [Kleine-Levin syndrome: a case report].
AB  - The purpose of this article is to report an original clinical case whose symptoms
      suggest a very peculiar pathology, because of its rarity, symptomatic expression
      and unclear etiopathogenesis: the Kleine-Levin Syndrome (KLS). During the
      regression of tonsillitis concomitant with an emotional shock, the 15-year-old
      patient exhibited a dramatic change in behaviour, at odds with his previous
      state, and accompanied by hypersomnia and confusion, megaphagia, irritability,
      hypersexuality and mood disorders. We observed a spontaneous and total regression
      of the symptoms after 12 days, except for the incomplete amnesia that proved to
      be persistent. Four months later, further to an ethylic drunkenness, the patient
      presented with a new and similar episode. The patient benefited from no medicinal
      treatment, even in the course of hypersomnia episodes and asymptomatic periods.
      After a clinical presentation of this patient, we will consider this case study
      from a more psychopathological angle by questioning the existence of a
      facilitating psychological profile. The discovery of an IQ equal to 86 from the
      scores of WISC-IV, and the identification of constructive visual difficulties
      made us suspect neurological disorders, but these abnormalities were not found
      during the completion of the Rey Complex Figure Test. The personality profile
      issued from the scores at the MMPI-A assessment was ranked as barely significant
      (type 2-4): indeed, it showed nothing specific to this patient. Literature data
      show that most of the patients presenting with a KLS have been seen by a
      psychiatrist at the time of the disease and diagnosed as suffering from hysteria,
      or schizophrenia, or bipolar disorders... Because of diagnostic wanderings, some
      patients have, hence, received inappropriate treatments. One should pay close
      attention to this very rare syndrome, on the border between neurology and
      psychiatry, since its diagnosis is essentially based on clinical features, and
      carefully think about the implementation of a medicinal treatment. This unique
      case seems unable to support our working hypothesis about the identification of a
      particular psychological profile in the KLS, but the question of an underlying
      fragility is still worth considering. We personally think that, even though links
      between the KLS and bipolar disorders have been suggested, this disease has to be
      considered as a separate entity.

PMID- 20159194
TI  - [Psychoactive substance use during pregnancy: a review].
AB  - All around the world, the potential consequences of the increasing use of
      psychoactive substances during pregnancy are a major public health concern. It is
      estimated that 20 to 30% of pregnant women use tobacco, 15% use alcohol, 3 to 10%
      use cannabis and 0.5 to 3% use cocaine. The estimation of tobacco consumption
      during pregnancy is better known as compared with alcohol and substance use
      prevalence during pregnancy, which remains under estimated or unknown. For
      example, in France, the prevalence of cannabis and cocaine use during pregnancy
      is unknown. In general, the prevalence of drug or alcohol use during pregnancy is
      estimated by extrapolating data from epidemiological studies conducted in the
      general population (in France or in other countries). However, drug or alcohol
      use in the general population may dramatically vary from one country to another.
      Even if some studies have reported the prevalence of alcohol or substance use in
      different countries around the world, most of them were based on the mother's
      interview. In most cases, the mother did not report exactly the amount of drugs
      or alcohol used. Further studies measuring alcohol or substance use in the
      mother's blood, hair or in the newborn's meconium are needed. In addition,
      different methodologies have been used in the literature (different types of
      interview, with or without biological measurements; different subjects included
      (in- or out-pregnant women, psychiatric comorbidities or not, different economic
      status, etc). Despite these methodological biases, the prevalence of drug or
      alcohol use increases in pregnant women, and in most cases, several drugs are
      associated. Most of the studies have used structured or semi-structured
      interviews such as the addiction severity index (ASI) or the alcohol use
      disorders identification test (AUDIT) to assess alcohol or drug consumption. In
      addition, the identification of risk factors for substance or alcohol use during
      pregnancy would allow the early detection of these high-risk pregnancies.
      Environmental factors such as low economic status or marital status may play an
      important role. Personality disorders may also contribute to substance or alcohol
      use during pregnancy. In fact, in most studies the quality of the obstetrical
      survey is lower in pregnant women using drugs or alcohol but it remains difficult
      to describe a specific at-risk profile in these pregnant women. Consumption of
      alcohol or of one or more psychoactive substances during pregnancy may have
      serious consequences on the pregnancy and on the child's development. Fetal
      alcoholism syndrome is the main etiology of mental retardation in France. We need
      to improve our knowledge of alcohol and substance use during pregnancy in order
      to target information for prevention campaigns and to implement specific mother
      and child medical care in high-risk populations.

PMID- 20159195
TI  - [Personal and social factors associated with the perception of health and the
      perception of happiness in a nonclinical adolescent population].
AB  - INTRODUCTION: A theoretical conceptualization of the relationship between health
      and happiness and associated factors was studied using a structural equation
      model. METHOD: Data from the Portuguese part of a World Health Organization
      collaborative study, health behavior in school-aged children [Currie C, Smith R,
      Boyce W, et al. HBSC, a WHO cross national study: Research protocol for the
      2001/2002 survey. Copenhagen: WHO; 2001], were used. A representative national
      sample (N=6131) of 11-, 13- and 15-year-old pupils was studied [Matos M.G.,
      Equipa do Projecto Aventura Social. A saude dos adolescentes portugueses: Quatro
      anos depois (La sante des adolescents portugais : quatre ans apres). Lisboa:
      Edicoes FMH; 2003] and data were analyzed for the purpose of this paper. Results
      showed a significant positive correlation between perception of health and
      perception of happiness. A group of personal and social factors was associated
      with this correlation. RESULTS: Results demonstrated that personal factors had
      more impact on health perception, and social factors had more impact on happiness
      perception. Adjustment fit indexes were good. Socioeconomic status (SES) was
      significantly associated with a positive health perception, and SES was also
      significantly but modestly associated with the perception of happiness.
      DISCUSSION: Results highlighted the importance of a holistic and positive
      approach to adolescent health. This study confirmed the importance of family,
      peer relationship and positive evaluation of the school on adolescents' health
      and well-being. Results may suggest that preventive interventions in school
      settings should target both personal factors (e.g., promoting social competence)
      and social factors (e.g., promoting social support and acceptance). Interventions
      should also target physical and mental health in order to help adolescents to
      cope with the daily challenges they meet.

PMID- 20159196
TI  - [Catatonia in a 14 year-old girl: treatment with clorazepam and carbamazepine, a
      10-year follow-up].
AB  - INTRODUCTION: Child and adolescent catatonia has been poorly investigated.
      Moreover, diagnosis criteria only exist for adult psychiatry, and there are no
      therapeutic guidelines. The aim of this paper is to describe the case of a 14
      year-old girl presenting an overlap between psychogenic and neuroleptic induced
      catatonia, acute treatment and ten year's follow-up. CASE REPORT: A 14-year-old
      Caucasian French girl, Elsa, was admitted in February 1998 to a University
      adolescent mental health center with an acute psychotic disorder. She showed
      agitation, impulsivity (sudden engagement in inappropriate behaviour), paranoid
      delusions, visual and auditory hallucinations, diurnal and nocturnal urinary
      incontinence, lack of self-care, inadequate food intake because of fear of
      poisoning, and vomiting after meals leading to rapid weight loss of 5 kg.
      Clinical examination, laboratory tests, EEG and RMI were normal. Toxicological
      tests were negative. Her IQ, assessed six months before admission, was in the
      dull average range (70-75). Elsa was treated with loxapine 150 mg per day for one
      week without improvement and this was then replaced by haloperidol 30 mg per day.
      One week after the start of haloperidol her agitation, impulsivity, and
      hallucinatory symptoms decreased. Twenty four days after loxapine introduction
      and 17 days after the haloperidol, her condition deteriorated rapidly over less
      than 48 hours. She exhibited immobility, minimal response to stimuli, staring and
      catalepsy with waxy flexibility. The diagnosis of catatonia was established.
      Examination revealed tremulous extremities, tachychardia (110 pm) and apyrexia.
      Creatine phosphokinase levels were 106 UI/l (normal range 0-250). Human
      immunodeficiency virus, hepatitis, listeria and Lyme serology were negative.
      Cerebrospinal fluid analysis was normal. Haloperidol was stopped and intravenous
      clonazepam 5mg/kg was begun. It was not possible to obtain signed consent from
      the two parents for Electroconvulsive therapy. The patient was transferred to a
      pediatric intensive care unit. The treatment was standard parenteral nutrition,
      nursing, intravenous clonazepam 0.05 mg/kg, with regular attendance by a child
      psychiatrist. Elsa stayed three weeks in this condition. She then began to notice
      the child psychiatrist, and a few days later she was able to carry out simple
      requests. Elsa was transferred to an adolescent psychiatric unit. As soon as she
      could eat by herself again, carbamazepine 400mg per day was begun. Her agitation
      reduced at a carbamazepine level of 7 mg/l. One month later her condition was
      stable. However, language difficulties persisted for a further six months. One
      year after the episode she scored 66 on a repeat IQ test and her RMI was normal.
      She exhibited no significant residual symptoms except some cognitive impairment.
      She integrated into a special education facility. These attempts to stop the
      carbamazepine were followed by depressed mood, aggressiveness and impulsivity;
      carbamazepine was finally stopped successfully after seven years. Ten years
      later, Elsa is the mother of two young children and is able to take care of them.
      She has never had a relapse of her psychotic disorder or catatonic state.
      DISCUSSION: The etiopathogenic diagnosis is problematic. Some indices in the
      familial history may suggest a traumatic event. But one to the total residual
      amnesia it was never confirmed, and traumatic catatonia are extremely rare.
      Normal CPK levels, with autonomic disturbance limited to tachycardia and the lack
      of resolution after discontinuance of medication, argues against a diagnosis of
      neuroleptic malignant syndrome (NMS). But CPK levels are non specific, and NMS
      without pyrexia has been described. The occurrence of the catatonic syndrome 21
      days after the first dose of a neuroleptic could be diagnostic. This case
      involved a non organic catatonic psychosis followed by neuroleptic induced
      catatonia. Catatonia is described as a risk factor for the development of NMS and
      some consider NMS to be a variant of malignant catatonia. The interest of this
      report is (1) it reinforces the need to be cautious before prescribing
      neuroleptics in adolescents presenting with symptoms of catatonia; (2) the
      complete recovery from catatonia after treatment with intensive care and more
      than three weeks of intravenous clonazepam without the use of ECT and (3) the
      effectiveness of carbamazepine over a long period of follow-up. Although trials
      on carbamazepine in catatonia are published, there are no data available for the
      control of residual symptoms or the long term prognosis, especially in child and
      adolescent psychiatry.

PMID- 20159197
TI  - [Washing, checking, and rumination: are the belief domains, obsessions and
      compulsions specific to OCD subtypes?].
AB  - AIM OF THE STUDY: The aim of the present study is to explore the validity of the
      Padua inventory and two belief questionnaires: the obsessive beliefs
      questionnaire (OBQ) and the interpretation of intrusions inventory (III).
      BACKGROUND: The Padua inventory is a 60-item self-report measurement of obsessive
      compulsive symptoms that measures both classic compulsive checking and cleaning
      behaviour as well as various types of obsessions, including impulses. Studies in
      several countries have provided support for the reliability and validity of the
      Padua inventory, including Italy, the Netherlands, North America, and the UK. The
      obsessive beliefs questionnaire assesses belief domains related to obsessive
      compulsive disorder (OCD): inflated responsibility, importance of thoughts,
      control of thoughts, overestimation of threat, perfectionism, and intolerance of
      uncertainty. It consists of 87 items representing dysfunctional assumptions
      covering these six domains. The interpretation of intrusions inventory consists
      of 31 items that refer to interpretations of intrusions that have occurred
      recently. Three of the above domains are represented: importance of thoughts,
      control of thoughts and responsibility. Data from clinical or non-clinical
      samples are used to study the factor structure, reliability, and convergent and
      divergent validity of these two questionnaires. METHODOLOGY: The three
      questionnaires were administrated to two groups of people as follows: 96 patients
      with OCD and 53 non-clinical subjects. The patients were selected from Rhone
      Alpes clinics and hospitals using DSM-IV criteria for diagnosis, prior to
      treatment. Diagnosis was based on semi-structured interview (MINI) and clinical
      interview by a trained psychiatrist using DSM-IV criteria. The second aim of the
      study was to investigate generality and congruence criterion of the subscales of
      the Padua inventory and beliefs domains in OCD symptom subtypes (rumination,
      washing, checking). The present study investigates whether specific OCD symptom
      subtypes are associated with specific symptom subscales and belief domains in an
      OCD sample. The criteria for categorizing a participant into an OCD symptom
      subtype was a score greater or equal to 75% of one main ritual. Fifty
      participants (52%) met these criteria: washing (n=20), rumination (n=16),
      checking (n=8), hoarding (n=1), perfectionism (n=3), and repeating (n=2). The
      other 46 subjects formed a non-specific symptom subtype (two or more rituals).
      Participants in the precision (perfectionism), the hoarding, and repeating
      symptom subtypes were excluded because of a small sample. RESULTS: The Padua
      inventory and the two questionnaires OBQ and III discriminated between French OCD
      and non clinical controls. In the OCD sample, the three subtypes (washers,
      rumination and checkers) did not differ from each other on total YBOCS score and
      total Padua score. The "washer" subjects scored higher than both "checker"
      subjects and subjects with rumination on the washing scale of the Padua
      inventory. The "checker" subjects scored higher than the two other subtypes on
      the checking scale. The impaired mental control and urges and worries of losing
      control scales failed to discriminate between the subjects with rumination and
      the two other (checking and washing) subtypes. The OBQ total and the six subscale
      scores failed to discriminate between the three OCD subtypes. These results were
      replicated with the III. The ANOVAs revealed that the participants in the
      rumination symptom subtype scored higher only on the importance/control of
      thoughts of the OBQ-44 than the participants in the checking subtype.
      Implications for future research are discussed.

PMID- 20159198
TI  - [Implementing a pluridisciplinary network of intimate partner violence
      prevention].
AB  - INTRODUCTION: The victims of a spouse's violence have a high risk of developing
      mental and physical health symptoms. The efforts aimed at preventing the
      consequences of domestic violence are encouraged by the current literature as
      well as the national and international recommendations. They highlight the fact
      that intervention and treatment programs have more or less failed. BACKGROUND:
      This publication introduces the main stages of the implementation of a network,
      the main goals of which are to improve the knowledge and professional practices
      aimed at the victims of domestic violence, and to enhance the continuation and
      quality of health and social care (screening, assessment and addressing). After
      relating the developments and the methodology of the victims' consultations
      carried out, we will show how such a network device enables one to exceed the
      usual practice limits. First, we point out certain specificities pertaining to
      postimmediate psychological care (psychological debriefing) of victims of
      intimate partner violence. METHODOLOGY: After presenting a specific methodology
      of assessment of the global situation of the victim, three illustrations of the
      specific consequences of domestic violence will be made, in order to highlight
      the interest of collaborating between professionals who are used to tackling this
      issue. First, is the way to empower women and help them to avoid assaults and
      thus prevent victimisation. The overall goal of this specific intervention is to
      teach women that they can end the cycle of perpetuating of intimate partner
      violence by learning safety factors, such as what to do if more violence occurs
      and where and how to seek assistance if it were to recur. Second, is to prevent
      the consequences of domestic violence on a child's development. It is based on
      the fact that children who witness domestic violence are negatively affected, as
      children who witness abuse are likely to experience a number of psychological
      symptoms. So the network proposes preventive measures and specific addressing to
      reduce the impact of violence. The third example relates to the high proportion
      of sexual assault among the nature of violence women suffer from. Victims of
      marital rape experience significant levels of negative mental and physical health
      symptoms. Network professionals have improved the screening of sexual assault in
      order to propose to the victims specific addressing, in terms of gynaecologic and
      psychological care. DISCUSSION: As a consequence, we deal with the professional
      and deontological positioning that the medical professionals have towards this
      device. The network device aims at going beyond the limits of the usual care,
      both through a pooling of knowledge and multidisciplinary practices. The
      establishment of common models of intervention (working groups), also suggests a
      best practice in relation to complex issues: the establishment of a network is a
      means of establishing the link between professionals. However, professionals in a
      network should routinely question their practice and ethics and to avoid
      "confusion of roles" - the risk of multidisciplinary and standard practices.
      Differences and professional specialisation are essential components of a care
      offer tailored to the clinical complexity of victims of domestic violence. It now
      appears necessary to assess the impact of this care at the social, health and
      psychological levels of victims of domestic violence.

PMID- 20159199
TI  - [Construct validation study of the Relationship Scales Questionnaire (RSQ) on an
      adult sample].
AB  - INTRODUCTION: The authors present the construct validity of the French version of
      the Relationship Scales Questionnaire (RSQ) designed by Griffin and Bartholomew
      (1994), which is the most widely-used self-report concerning adult attachment.
      OBJECTIVES: To improve knowledge on the psychometric properties of the RSQ by
      studying the construct validity on a sample of adults. METHOD: Subjects were
      recruited in a primary social care setting in Paris, France, and asked to fill in
      the RSQ twice: the first time just before meeting the social worker in charge,
      the second time, at home, with a prestamped form, two days later. A questionnaire
      on sociodemographic and economic variables was also filled in during the first
      time. Statistical analyses were conducted using Exploratory Factor Analysis with
      orthogonal rotation. The reliability was studied using Cronbach's coefficient for
      each new scale from the factor analysis. The test-retest reliability was studied
      for the prototypic scales and for the scales from the factor analysis, using the
      intra-class correlation method. RESULTS: One hundred and twenty-six subjects were
      recruited and completed the two forms (mean interval: 2.16 days). The factor
      analysis gives a three-factor structure explaining 48% of the total variance. The
      three factors were: factor 1 "Avoidance" with seven items explaining 21% of the
      total variance; factor 2 "Anxiety in the relationships" (five items) explaining
      14% of total variance and factor 3 "Security" (five items) explaining 11% of the
      total variance. Cronbach's coefficient was low for the prototypical scales (0.41
      for "secure", 0.54 for "fearful", 0.22 for "preoccupied", and moderate for
      "dismissive" (0.64). It was moderate for the scales designed from the factor
      analysis (0.66 for F1, 0.69 for F2 and 0 .60 for F3). The Intraclass Coefficients
      (ICC) were modest for the four prototypical scales (ICC<0.70) and were good for
      the scales designed from the factor analysis (F1: ICC=0.80; F2: ICC=0.85 and F3:
      ICC=0.78). DISCUSSION: The construct validity studied on an adult sample confirms
      the good psychometric properties of the RSQ considering the factor analysis, the
      test-retest short time reliability and the internal consistency. The factor
      analysis with three factors provides a different structure of classical
      descriptions with only two factors, but confirms the most recent results on
      Attachment Self-Reports that find a factor concerning security and two factors
      concerning management of insecurity (avoidance and anxiety in relationships). To
      be confirmed, the results require further research (confirmatory factor analysis,
      larger sample, other type of population).

PMID- 20159200
TI  - [Cholinesterase inhibitors and depression in the elderly].
AB  - BACKGROUND: Depression in the elderly is characterized by an atypical expression
      with delusion, major anxiety, behaviour disorders, somatic complains or cognitive
      impairment. These clinical aspects are suspected to be at the origin of the poor
      response to antidepressants observed in these cases. It is currently indicated to
      add sedative medicines to antidepressants, when a major anxiety is associated
      with depression, or an antipsychotic in the delusional forms of the depression.
      However, it is not consensually established that cholinesterase inhibitors can be
      helpful in depression with cognitive impairment. Cholinesterase inhibitors are
      efficient among patients with Alzheimer disease. They improve cognitive
      performances and slow down the degenerative process during the first years of
      treatment. Today, new findings on neurobiological mechanisms of depression
      involve a located degenerative process, with some similar anomalies in the brain
      in both depression and pre-Alzheimer states. New therapeutic trials have shown
      that cholinesterase inhibitors can be also efficient on depressed symptoms among
      patients with Alzheimer disease. These evidences support the hypothesis that the
      association of cholinesterase inhibitors to antidepressants can bring more
      benefits to depressed elderly patients. AIM: Through a review of the literature
      and a case report, we tried to specify whether cholinesterase inhibitors can be
      useful in the treatment of depression among the elderly. CASE REPORT: We report
      the case of a 68-year-old man who had presented, four years ago, a second episode
      of major depression with a cognitive impairment. Treated with an antidepressant
      (venlafaxine), the improvement was poor with major anxiety, slow thoughts, and an
      evidence of a persistent cognitive impairment. Despite normal cerebral scanning
      images, we decided to add a cholinesterase inhibitor (donepezil) to the same
      antidepressant. With this association, we rapidly obtained a total remission from
      depression with restitution of cognitive performances. This state is still
      maintained until today (four years after the last depressive episode) with no new
      mood relapses. Recent cerebral scanning images did not show any degenerative
      process. CONCLUSION: The association of cholinesterase inhibitors and an
      antidepressant seems a good alternative, when the response to antidepressant is
      partial in depression with cognitive impairment in the elderly. However, further
      therapeutic trials are still needed, to prove the usefulness of cholinesterase
      inhibitors among depressed elderly patients.

PMID- 20159201
TI  - [7th neuroplasticity international workshop. October 10-11, 2009].

PMID- 20159202
TI  - Anticipatory anhedonia in schizophrenia subjects.

PMID- 20159204
TI  - Variety is the spice of life: isn't it?

PMID- 20159205
TI  - The ST injury vector: electrocardiogram-based estimation of location and extent
      of myocardial ischemia.
AB  - BACKGROUND: Analysis of ST deviations from the 12-lead electrocardiogram allows
      for estimation of a spatial ST injury vector. The goal of the present study was
      to compare the location and extent of transmural myocardial ischemia evaluated by
      myocardial perfusion imaging with the direction and magnitude of the ST injury
      vector. METHODS: Twelve-lead electrocardiograms were recorded from 75 acute
      myocardial infarction patients with single-vessel disease and thrombolysis in
      myocardial infarction (TIMI) flow 0/1 (30 left anterior descending [LAD], 28
      right coronary artery [RCA], 17 left circumflex artery [LCX]). ST deviations were
      measured in the J point in all leads and used to estimate ST injury vectors for
      each patient. Myocardial perfusion imaging was performed to evaluate the extent
      and location of myocardial ischemia at the time of coronary intervention.
      RESULTS: Ninety-two percent of the patients showed ST injury vectors within the
      expected directional range for the identified anatomic segment of ischemia by
      myocardial perfusion imaging. ST injury vector direction separated LAD, RCA, and
      LCX occlusion patients; 90% of the LAD patients showed anterior vectors, 82% of
      the RCA patients showed posteroinferoseptal vectors, and 59% of the LCX patients
      showed posteroinferolateral vectors. Eight patients did not fulfill the ST
      elevation criteria for ST elevation myocardial infarction but showed anterior ST
      depression and prominent ST injury vectors in the posterior torso direction.
      There was a moderate correlation between the extent of ischemia and ST injury
      vector magnitude for the ischemic patients, r = 0.29. CONCLUSION: We found strong
      agreement between the direction of the ST injury vector and the location of
      myocardial ischemia. The ST injury vector may be the key to higher diagnostic
      accuracy for inferobasal transmural ischemia and may help distinguishing between
      RCA and LCX occlusions in the acute phase.

PMID- 20159206
TI  - The two views of emotion in psychosomatic research.

PMID- 20159207
TI  - Evaluation of the structure of Brazilian State-Trait Anxiety Inventory using a
      Rasch psychometric approach.
AB  - OBJECTIVE: This study evaluates the State-Trait Anxiety Inventory (STAI)
      structure using a Rasch psychometric approach, and a refined and shorter STAI
      version is proposed. METHODS: A cross-sectional study was performed with 900
      inpatients scheduled for elective surgery. Age varied from 18 to 60 years
      (American Society of Anesthesiologists physical status I-III). Demographic
      information was collected using a structured questionnaire. The measuring
      instrument (the STAI) was applied to all patients in the afternoon before the
      surgery and prior to the patients receiving preoperative sedatives. RESULTS:
      Rasch analysis of the state and trait anxiety scales was performed separately.
      This analysis demonstrated that the original format of state and trait scales
      fails to show invariance across the trait-state anxiety level, which results in
      the unstable performance of items. The refined scale was retested in two
      subsequent random samples of 300 subjects each, and the results were confirmed.
      The performance was adequate regardless of gender. In the analysis, some items of
      the state scale (items 3,4,9,10,12,15, and 20) were deleted due to poor fit
      statistics. The remaining 13 items showed unidimensionality, local independence,
      and adequate index of internal consistency. Also, the original trait scale
      displayed several weaknesses. First, the four-point Likert response scale proved
      to be inadequate, and threshold disorders were found in all 20 items. Also, the
      original trait scale showed insufficient item-trait interaction and several
      individual item misfits. Following the rescoring process, and retesting in a
      second random sample, items were excluded (namely Items 3, 4, 11, 13, 14, 15, 18,
      and 19). The refined version showed local independence, unidimensionality, and
      adequate fit statistics. DISCUSSION: The results indicate that the application of
      the Rasch model led to the refinement of the classic STAI state and trait scales.
      In addition, they suggest that these shorter versions have a more suitable
      psychometric performance and are free of threshold disorders and differential
      item functioning problems.

PMID- 20159208
TI  - Social phobia and depression: prevalence and comorbidity.
AB  - BACKGROUND: Social phobia may seriously impair the functioning of affected
      individuals. It is frequently associated with other mental disorders. AIMS: To
      estimate the co-occurrence of social phobia with major depressive disorder (MDD)
      and to analyze their interaction. METHOD: Subjects were 18,980 individuals, aged
      15 years or older, representative of the general population of the United
      Kingdom, Germany, Italy, Spain and Portugal, who were interviewed by telephone.
      DSM-IV diagnoses were made with the Sleep-EVAL system. RESULTS: The point
      prevalence for social phobia was 4.4% (95% confidence interval: 4.1-4.7%) of the
      sample. It was higher in women (odds ratio: 1.6) and decreased with age. MDDs
      were found in 19.5% of participants with social phobia. Co-occurrence of another
      anxiety disorder was high and increased when a MDD was present (65.2%). The odds
      of developing a major depressive episode 2 years after the appearance of the
      social phobia was of 5.74. CONCLUSIONS: Social phobia is highly prevalent in the
      general population. It increases the risk of developing a MDD and has a high
      comorbidity with other mental disorders. Social phobia is often present in the
      course of depression, more obviously during remission period of MDD. Physicians
      must explore and treat more systematically this frequent pathology.

PMID- 20159209
TI  - The effectiveness of bibliotherapy in alleviating tinnitus-related distress.
AB  - OBJECTIVE: The present study examined the efficacy of bibliotherapy in assisting
      individuals experiencing distress related to tinnitus. METHODS: One hundred sixty
      two tinnitus sufferers from Australia participated in a study designed to examine
      the effectiveness of a cognitive-behaviorally based self-help book in reducing
      distress. To maximize the ecological validity of the findings, we excluded no
      individuals interested in treatment for tinnitus-related distress. RESULTS: The
      experimental condition lost 35% of participants at postassessment, compared to
      10% in the control group. In an analysis of participants who completed
      postintervention assessment, those assigned to the intervention condition, who
      received a tinnitus self-help book, showed significantly less tinnitus-related
      distress and general distress 2 months later compared to those assigned to the
      waiting list control condition. The intervention group's reduction in tinnitus
      related distress and general distress from preintervention to postintervention 2
      months later was significant, and these participants maintained a significant
      reduction in distress on follow-up 4 months after they received the tinnitus self
      help book. A long-term follow-up of all participants, who at that time had
      received the book at least a year previously, showed a significant reduction in
      tinnitus distress. Although these group differences and pre-post changes were
      significant, effect sizes were small. Intention-to-treat analyses showed no
      significant effect for between-groups analyses, but did show a significant effect
      for the 1-year follow-up pre-post analysis. CONCLUSION: Information on the
      effectiveness of using a self-help book, without therapist assistance, in
      alleviating distress is important, as bibliotherapy can provide inexpensive
      treatment that is not bound by time or place.

PMID- 20159210
TI  - Patients with medically unexplained symptoms and their significant others:
      illness attributions and behaviors as predictors of patient functioning over
      time.
AB  - OBJECTIVE: Previous research suggests that medically unexplained symptoms (MUS)
      are maintained in an interpersonal context. The current study examined MUS
      concurrently and prospectively by measuring specific interpersonal predictors of
      symptom severity and health care use. METHODS: A total of 127 patients with MUS
      and their significant others were recruited through primary care offices and
      assessed with self-report questionnaires and structured interviews about illness
      attributions, illness behavior and responses, relationship quality, symptom
      severity, and health care use at baseline and 6-month follow-up. RESULTS: Illness
      attributions and interpersonal illness behaviors of patients with MUS were cross
      sectionally associated with illness attributions and responses of the patients'
      significant others. Relationship quality was related to specific illness
      behaviors and responses. Symptom severity at baseline was predicted by patients'
      somatic illness attributions. Symptom severity at 6-month follow-up was predicted
      by somatic illness attributions of patients and withdrawal of patients'
      significant others at baseline, but these predictors became insignificant when
      correcting for baseline symptomatology. Health care use at baseline was predicted
      by a greater amount of coping behavior and higher anxiety scores of patients, and
      health care use at 6-month follow-up was predicted by more attention-seeking
      behaviors and health care use of patients at baseline. CONCLUSION: The results
      document the interpersonal influences on the maintenance of MUS. The perspective
      of significant others should be considered for enhancement of psychological
      approaches to the treatment of patients with MUS.

PMID- 20159211
TI  - The psychological impact of accidents on recreational divers: a prospective
      study.
AB  - OBJECTIVE: The present study aimed to examine the medium and long term
      psychological impact of diving accidents on the victims (n=52), compared with the
      impact on two control groups: the victim's diving "buddy" (n=40) who simply
      witnessed the accident, and a second control from the same boat who did not dive
      with the victim (n=38). METHODS: This was a prospective cohort study of the
      impact of an accident on the victims who attended the Hyperbaric Unit, in
      comparison with the two control groups. Pre-accident psychological morbidity was
      assessed using the General Health Questionnaire. Trauma symptoms were assessed
      using the Revised Impact of Events Scale at 3, 6 and 12 months post accident.
      RESULTS: The accident victims endorsed more trauma symptoms and experienced them
      more intensely and for longer, compared with the two control groups. CONCLUSION:
      A significant minority of diving accident victims (between 25% and 50%) continued
      to suffer from the psychological impact of the accident, some for over a year.
      This has important implications for their future health care, for their safety on
      subsequent dives, and for dive training.

PMID- 20159212
TI  - Is alexithymia a risk factor for major depression, personality disorder, or
      alcohol use disorders? A prospective population-based study.
AB  - OBJECTIVE: Disagreements concerning the stability of alexithymia and its ability
      to predict subsequent psychiatric disorders prevail. The aim of this 7-year
      follow-up study was to examine whether alexithymia predicts subsequent major
      depression, personality disorder, or alcohol use disorders in a population-based
      sample. METHODS: The four-phase Kuopio Depression Study (KUDEP) was conducted in
      the eastern part of Central Finland. The study population (aged 25-64, n=2050)
      was randomly selected from the National Population Register. Data were collected
      in 1998, 1999, and 2001. In 2005, a subsample (n=333, 43 were excluded) of the 3
      year follow-up population (1998-2001) was gathered and their diagnoses of mental
      disorders were confirmed by the Structure Clinical Interview for DSM-IV Axis I
      (SCID-I). Alexithymia was measured using the Toronto Alexithymia Scale (TAS-20)
      and depressive symptoms using the Beck Depression Inventory (BDI-21). For both of
      these measures, two groups were formed based on the median of their sum score
      (summing the 1998, 1999, and 2001 scores). Logistic regression analyses were
      performed. RESULTS: BDI sum scores, but not those of TAS, were associated with
      subsequent major depressive disorder, personality disorder, and alcohol use
      disorders in 2005. The BDI sum scores explained 35.7% of the variation in
      concurrent TAS sum scores. CONCLUSION: Alexithymia did not predict diagnoses of
      major depressive disorder, personality disorder, or alcohol use disorders.
      Alexithymia was closely linked to concurrent depressive symptoms. Thus,
      depressive symptoms may act as a mediator between alexithymia and psychiatric
      morbidity.

PMID- 20159213
TI  - Commentary on the paper "Is alexithymia a risk factor for major depression,
      personality disorder, or alcohol use disorders? A prospective population-based
      study".

PMID- 20159214
TI  - Health-related quality-of-life profiles in nonalexithymic and alexithymic
      subjects from general population.
AB  - OBJECTIVE: Earlier studies have shown an association between alexithymia and
      health-related quality of life (HRQoL). There has been some controversy as to
      whether this is attributable solely to psycho-social domains of HRQoL or also to
      physical domains. Furthermore, there are no studies on HRQoL profiles in
      representative general population samples controlling for sociodemographic
      variables, mental health and somatic health. METHODS: The study forms part of the
      Health 2000 Study. Altogether 5090 participants from general population, aged 30
      97 years, filled in the 20-item Toronto Alexithymia Scale and the 15D HRQoL
      scale. Depressive and anxiety disorders were assessed in a structured psychiatric
      interview. Physical health was examined by physicians. The 15-dimension HRQoL
      profiles of both alexithymic and non-alexithymic subjects were obtained by
      analysis of covariance, controlling for sociodemographic and health-related
      variables. RESULTS: The alexithymic group had significantly (P<.001) lower mean
      scores on every dimension of the 15D even after controlling for confounding
      demographic variables, somatic diagnoses and depressive and anxiety disorders.
      The differences were greatest in the psycho-social domains. CONCLUSIONS:
      Alexithymia seems to be a personality trait with a statistically significant
      association to every dimension of HRQoL, not only to psychosocial domains.
      However, the associations between alexithymia and some somatic dimensions may be
      of little clinical significance.

PMID- 20159215
TI  - The Beliefs about Emotions Scale: validity, reliability and sensitivity to
      change.
AB  - OBJECTIVE: Beliefs about the unacceptability of experiencing or expressing
      negative emotions have been noted in individuals with a range of problems,
      including chronic fatigue syndrome (CFS), irritable bowel syndrome, somatization
      disorder, depression, eating disorders, social phobia, posttraumatic stress
      disorder, and borderline personality disorder. These beliefs are likely to have
      implications for emotion regulation and processing, and are addressed explicitly
      or implicitly within many therapies including cognitive behavior therapy (CBT),
      mindfulness-based cognitive therapy (MBCT), and Acceptance and Commitment Therapy
      (ACT). This article describes the development, validation, and internal
      reliability of the Beliefs about Emotions Scale (BES), a self-report
      questionnaire to assess such beliefs. METHODS: The new scale was completed by
      people with CFS (n=121) and healthy controls (n=73). Twenty-two individuals with
      CFS completed the scale before and after CBT. RESULTS: People with CFS had
      significantly higher scores on this new questionnaire than healthy controls.
      Principal components analysis identified one factor, and the scale had high
      internal consistency (0.91). Scores on the BES were most highly correlated with a
      measure of negative perfectionism (r=0.59) and also showed significant
      correlations with measures of dysfunctional attitudes, self-sacrifice,
      depression, anxiety, and fatigue. When completed before and after CBT for CFS,
      the questionnaire was sufficiently sensitive to detect a significant reduction in
      endorsement of unhelpful beliefs about emotions. CONCLUSION: The new Beliefs
      about Emotions Scale showed good internal reliability, validity and sensitivity
      to change.

PMID- 20159216
TI  - Cost outcomes on a medical psychiatry unit.

PMID- 20159217
TI  - Managing complex patients on a medical psychiatric unit: an observational study
      of university hospital costs associated with medical service use, length of stay,
      and psychiatric intervention.
AB  - OBJECTIVE: Although there is a suggestion that the medical psychiatric unit (MPU)
      may reduce length of hospital stay (LOS), little is known about costs in terms of
      medical service use and psychiatric interventions in MPU care. METHOD: A record
      linkage study was conducted, linking cost data of hospital medical service use,
      LOS, and hospital psychiatric interventions to patients admitted to the MPU of
      the Maastricht University Medical Centre (MUMC) between 1998 and 2004. The data
      set was analyzed to enable comparison between cost changes of the same complex
      patient population following either MPU index admission or index admissions to
      reference MUMC medical wards. RESULTS: Comparisons revealed lower costs of
      medical service use in favor of the MPU (-euro104; 95% CI -euro174 to -euro35;
      P<.01). However, cost of psychiatric intervention and cost of LOS were higher
      after MPU admission (respectively, +euro165; 95% CI +euro25 to +euro305; P<.05;
      and +euro202; 95% CI +euro170 to +euro235; P<.001). Total costs were higher after
      MPU admission compared to medical ward admission (+euro263; 95% CI +euro68 to
      +euro458; P<.05). These differences were not moderated by somatic diagnosis or
      previous pattern of admissions. CONCLUSION: The findings suggest that patients at
      the interface of psychiatric and somatic morbidity are diagnosed and treated
      adequately at the MPU, leading to a decrease in medical service use and an
      appropriate increase in exposure to psychiatric interventions. These results are
      specifically generalizable to MPUs with a focus on psychosomatic conditions, for
      instance, somatoform disorders or affective disorders with comorbid somatic
      diseases. However, failure to show cost savings in terms of LOS compared to
      medical wards outweighs cost-benefit derived from lower medical service use,
      suggesting that MPU activities may gain in cost-effectiveness if shifted more to
      outpatient psychosomatic care solutions.

PMID- 20159218
TI  - Can we increase adherence to treatment recommendations of the consultation
      psychiatrist working in a general hospital? A systematic review.
AB  - BACKGROUND: Adherence to advice given by the consultation-liaison (CL)
      psychiatrist is a prerequisite for the effectiveness and success of psychiatric
      consultation. It is unknown which factors are associated with better adherence to
      advice. AIM: To review the adherence of consultees with advice given by the
      psychiatrist during inpatient consultation. METHOD: Systematic literature review.
      RESULTS: Eighteen studies reported on the level of adherence with recommendations
      given by the consultation psychiatrist in a hospital setting. All were
      retrospective cohort studies conducted before 1998. Thirteen of these reported on
      the association between clinical variables and the level of adherence. The median
      level of adherence with diagnostic advice was 56% (range 29-75%), with medication
      advice 79% (range 68-98%), and with discharge advice 91% (range 85-95%). Patient
      related variables were not associated with adherence, nor were consultee-related
      variables. Consultant-related variables associated with adherence were level of
      professional expertise, organizing liaison activities, following up on patients
      after initial consultation, and prescription of medication by the consultant
      during the consultation. CONCLUSION: This review provides evidence for a role of
      consultant characteristics and an active approach of the consultant in terms of
      CL activities as well as consultation procedures, in attaining adherence to
      advice. Prospective qualitative research is needed to identify consultation
      methods that may further enhance adherence.

PMID- 20159219
TI  - Expectations in rheumatoid arthritis.

PMID- 20159220
TI  - Embodied effects of mindfulness-based cognitive therapy.

PMID- 20159221
TI  - The HSCL-20: one questionnaire, two versions.

PMID- 20159222
TI  - Temperamental attention and activity, classroom emotional support, and academic
      achievement in third grade.
AB  - The purpose of this study is to examine the interplay of children's temperamental
      attention and activity (assessed when children were 4-and-a-half years old) and
      classroom emotional support as they relate to children's academic achievement in
      third grade. Particular focus is placed on the moderating role of classroom
      emotional support on the relationship between temperament (attention and activity
      level) and academic achievement. Regression analyses indicated that children's
      attention and activity level were associated with children's third grade reading
      and mathematics achievement, and classroom emotional support was associated with
      children's third grade reading and mathematics achievement. In addition,
      classroom emotional support moderated the relation between children's attention
      and reading and mathematics achievement, such that attention mattered most for
      reading and mathematics achievement for children in classrooms with lower
      emotional support. Findings point to the importance of understanding how
      children's temperament and classroom emotional support may work together to
      promote or inhibit children's academic achievement.

PMID- 20159223
TI  - The relation of student behavior, peer status, race, and gender to decisions
      about school discipline using CHAID decision trees and regression modeling.
AB  - Peer nominations and demographic information were collected from a diverse sample
      of 1493 elementary school participants to examine behavior (overt and relational
      aggression, impulsivity, and prosociality), context (peer status), and
      demographic characteristics (race and gender) as predictors of teacher and
      administrator decisions about discipline. Exploratory results using
      classification tree analyses indicated students nominated as average or highly
      overtly aggressive were more likely to be disciplined than others. Among these
      students, race was the most significant predictor, with African American students
      more likely to be disciplined than Caucasians, Hispanics, or Others. Among the
      students nominated as low in overt aggression, a lack of prosocial behavior was
      the most significant predictor. Confirmatory analysis using hierarchical logistic
      regression supported the exploratory results. Similarities with other biased
      referral patterns, proactive classroom management strategies, and culturally
      sensitive recommendations are discussed.

PMID- 20159224
TI  - School profiles of at-risk student concentration: differential growth in oral
      reading fluency.
AB  - The present study provides a data-driven approach to identifying groups of
      schools based on the concentration of at-risk students the school serves. The
      percentage of English language learners, minority students, and students eligible
      for free or reduced priced lunch were used as indicators in a latent profile
      analysis of 569 schools. The goal of the present study was to determine whether
      school-level average student reading performance varied as a function of the
      groups identified in the latent profile analysis. To do so, groups extracted by
      the latent profile analysis were used as school-level predictors of growth in
      oral reading fluency, which was modeled at the within-student level of a three
      level hierarchical growth curve model. Oral reading fluency was measured at four
      points during the year in a large cross-sectional sample of first-, second-, and
      third-grade students. Results indicated that schools were able to be classified
      into four distinct groups based on their concentrations and types of at-risk
      students. Further, in all three grades, there were significant differences
      between the four identified groups observed in average reading fluency scores at
      the beginning of the year, the end of the year, and growth during the year
      indicating that groups based on school-concentration of at-risk students were
      significantly related to average student achievement in reading ability.

PMID- 20159225
TI  - [Solution to case 13. Lipomatous macrodystrophy of the foot associated to
      lipomatosis of the plantar nerve].

PMID- 20159226
TI  - [Solution to case 14. Pleomorphic sarcomatoid carcinoma of the lung].

PMID- 20159227
TI  - Degrees of fictitiousness.

PMID- 20159228
TI  - Nonsteroidal anti-inflammatory drugs in ophthalmology.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly employed in
      ophthalmology to reduce miosis and inflammation, manage scleritis, and prevent
      and treat cystoid macular edema associated with cataract surgery. In addition,
      they may decrease postoperative pain and photophobia associated with refractive
      surgery and may reduce the itching associated with allergic conjunctivitis. In
      recent years, the U.S. Food and Drug Administration has approved new topical
      NSAIDs, and previously approved NSAIDs have been reformulated. These additions
      and changes result in different pharmacokinetics and dosing intervals, which may
      offer therapeutic advantages. For example, therapeutic effects on diabetic
      retinopathy and age-related macular degeneration may now be achievable. We
      provide an updated review on NSAIDs and a summary of their current uses in
      ophthalmology with attention to potential future applications.

PMID- 20159229
TI  - Uveal effusion syndrome.
AB  - The terms uveal effusion, choroidal effusion, ciliochoroidal effusion,
      ciliochoroidal detachment, and choroidal detachment have been used
      interchangeably in the literature. These labels all describe an abnormal
      collection of fluid that expands the suprachoroidal space, producing internal
      elevation of the choroidal. There are various inflammatory and hydrostatic
      conditions that can cause uveal effusion, but in some cases no obvious cause
      exists. In this setting, patients are thought to have a distinct, primary
      abnormality of the choroid or sclera, called uveal effusion syndrome (UES). UES
      may be idiopathic, or associated with hypermetropia, and should be considered a
      diagnosis of exclusion. Histological studies show amorphous glycosaminoglycan
      like material filling the interfibrillary spaces of excised scleral tissue, with
      disruption of collagen fibers. In some patients there may be reduced
      macromolecular diffusion that interferes with the normal transscleral egress of
      albumin out of the eye, perhaps causing choroidal fluid retention due to altered
      osmotic forces. An alternative, and perhaps complementary hypothesis, is that
      swollen sclera compresses the transscleral vessels with resulting fluid
      retention. Patients with UES are most typically middle-aged men who have a
      relapsing remitting clinical course. There is often co-existing, shifting
      subretinal fluid that may involve the macula. Chronic disease may lead to
      secondary retinal pigment epithelial (leopard spot) changes and permanently
      reduced visual acuity. Treatment with systemic steroids does not appear to be
      effective. Surgical decompression of the vortex veins as they pass through the
      sclera has been described, but the most common treatment is full-thickness
      sclerectomies to provide an exit for choroidal fluid. The largest case series
      suggests that this produces an anatomic improvement in approximately 83% of
      treated eyes after a single procedure and in about 96% after one or two
      procedures. Final visual acuity improves by two or more lines in 56% of the eyes,
      is stable in 35%, and worsens in 9%. Although extremely rare, UES is a serious
      condition that is difficult to treat and can lead to severe and permanent visual
      loss in both eyes.

PMID- 20159231
TI  - Topical ophthalmic cyclosporine: pharmacology and clinical uses.

PMID- 20159232
TI  - Perceptual learning: functions, mechanisms, and applications.

PMID- 20159233
TI  - Editorial to special issue in Water Research: emerging contaminants in water.

PMID- 20159234
TI  - Re-evaluation of IgG4 in systemic fibroinflammatory disease with intracardiac
      involvement.

PMID- 20159235
TI  - Grading of skin sebaceous carcinoma.

PMID- 20159236
TI  - Cholinergic neurotransmission and muscarinic receptors in the enteric nervous
      system.
AB  - There is a rich knowledge of the enteric nervous system (ENS), especially the
      neurochemical and neurophysiological properties of enteric neurons and how they
      communicate in neural circuits underlying intestinal reflexes. The major pathways
      of excitatory transmission within the ENS are mediated by cholinergic and
      tachykinergic transmission, with transmitters Acetylcholine (ACh) and Tachykinins
      (TK), respectively, producing excitatory potentials in post-synaptic effectors.
      This review focuses on the cholinergic pathways of the ENS. The cholinergic
      circuitry of the ENS is extensive and mediates motility (muscular) and secretory
      (mucosal) reflexes, in addition to intrinsic sensory and vascular reflexes. The
      capacity of ACh to mediate multiple physiologically significant intestinal
      reflexes is largely due to having multiple sites of neuronal and non-neuronal
      release and reception within the intestine. This review will concentrate on one
      of two classes of ACh receptors, Muscarinic receptors (mAChr), in particular
      their location and function in mediating synaptic transmission within enteric
      circuits underlying intestinal reflexes.

PMID- 20159237
TI  - The role of pharmacogenomics in improving the management of asthma.
AB  - There is a large amount of interindividual variability in both therapeutic and
      adverse responses to asthma therapies. Genetic variability can account for 50% to
      60% of this variability. Pharmacogenomics holds out the promise of allowing
      clinicians to prospectively choose therapies that have the greatest likelihood to
      be effective for individual patients and to avoid those that might have a high
      likelihood of producing adverse effects. In this article we review the principles
      of pharmacogenomic investigation. We explore the data developed from the early
      pharmacogenomic studies with the most common asthma therapies. Furthermore, we
      explore the potential use of pharmacogenomics, as well as caveats in interpreting
      such information.

PMID- 20159238
TI  - Personalized medicine for patients with asthma.

PMID- 20159239
TI  - Achieving asthma control in patients with moderate disease.
AB  - Patients with moderate asthma are symptomatic on an ongoing basis. They are
      usually treated initially with low-dose inhaled corticosteroids (ICSs)
      supplemented with a short-acting bronchodilator as a rescue medication. Most
      steroid-naive patients will achieve good control with this strategy. For patients
      in whom adherence, inhaler technique, environmental control, and comorbidities
      have been addressed but who still have uncontrolled symptoms, the addition of a
      long-acting beta-adrenergic agonist should be considered. Some patients might
      require a higher dose of ICS. Leukotriene receptor antagonists might be
      considered as alternate initial therapy or as an add-on to maintenance therapy
      with an ICS. All patients should receive a structured education program
      emphasizing the need for ongoing maintenance treatment, even when control is
      achieved. Patients should also be provided with a written action plan that
      clearly explains which additional anti-inflammatory therapy should be taken if
      asthma symptoms worsen. The most effective strategy in this situation has been
      shown to be the quadrupling of the maintenance dose of ICS.

PMID- 20159240
TI  - Key advances in mechanisms of asthma, allergy, and immunology in 2009.
AB  - The year 2009 was marked by rapid progress in understanding cellular and chemical
      mechanisms in the pathogenesis of asthma and other allergic disorders. Studies
      published in the Journal of Allergy and Clinical Immunology described advances in
      our knowledge of signaling molecules and pathways, cytokines, and activation and
      tolerance in asthma and murine models of this disease; food allergy; anaphylaxis
      and immediate hypersensitivity; mast cells and their disorders; atopic
      dermatitis; allergic conjunctivitis; nasal polyposis; and hypereosinophilic
      syndromes. Additional studies provided novel information about the induction and
      regulation of allergic inflammation and the genetic determinants of asthma and
      responsiveness to asthma therapy. Critical features of these studies and their
      potential effect on human atopic disorders are summarized here.

PMID- 20159243
TI  - Genetics and biology of asthma 2010: La' ci darem la mano...

PMID- 20159242
TI  - Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ
      regions.
AB  - BACKGROUND: Asthma is a heterogeneous disease that is caused by the interaction
      of genetic susceptibility with environmental influences. Genome-wide association
      studies (GWASs) represent a powerful approach to investigate the association of
      DNA variants with disease susceptibility. To date, few GWASs for asthma have been
      reported. OBJECTIVES: A GWAS was performed on a population of patients with
      severe or difficult-to-treat asthma to identify genes that are involved in the
      pathogenesis of asthma. METHODS: A total of 292,443 single nucleotide
      polymorphisms (SNPs) were tested for association with asthma in 473 The
      Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens
      (TENOR) cases and 1892 Illumina general population controls. Asthma-related
      quantitative traits (total serum IgE, FEV(1), forced vital capacity, and
      FEV(1)/forced vital capacity) were also tested in identified candidate regions in
      473 TENOR cases and 363 phenotyped controls without a history of asthma to
      analyze GWAS results further. Imputation was performed in identified candidate
      regions for analysis with denser SNP coverage. RESULTS: Multiple SNPs in the
      RAD50-IL13 region on chromosome 5q31.1 were associated with asthma: rs2244012 in
      intron 2 of RAD50 (P = 3.04E-07). The HLA-DR/DQ region on chromosome 6p21.3 was
      also associated with asthma: rs1063355 in the 3' untranslated region of HLA-DQB1
      (P = 9.55E-06). Imputation identified several significant SNPs in the T(H)2 locus
      control region 3' of RAD50. Imputation also identified a more significant SNP,
      rs3998159 (P = 1.45E-06), between HLA-DQB1 and HLA-DQA2. CONCLUSION: This GWAS
      confirmed the important role of T(H)2 cytokine and antigen presentation genes in
      asthma at a genome-wide level and the importance of additional investigation of
      these 2 regions to delineate their structural complexity and biologic function in
      the development of asthma.

PMID- 20159244
TI  - Long-acting beta-agonists and inhaled corticosteroids: is the whole greater than
      the sum of its parts?

PMID- 20159246
TI  - Age-related association of fine particles and ozone with severe acute asthma in
      New York City.
AB  - BACKGROUND: Ambient fine particles (particular matter <2.5 microm diameter
      [PM(2.5)]) and ozone exacerbate respiratory conditions including asthma. There is
      little documentation determining whether children are more vulnerable to the
      effects of ambient pollution than adults, or whether pollution causes life
      threatening episodes requiring intensive care unit (ICU) admission. OBJECTIVE: We
      investigate the relationship between severe asthma morbidity and PM(2.5) and
      ozone in the warm season, and determine whether there is an age-related
      susceptibility to pollution. METHODS: Daily time-series analysis of 6008 asthma
      ICU admissions and 69,375 general (non-ICU) asthma admissions in 4 age groups
      (<6, 6-18, 19-49, and 50+ years) in 74 New York City hospitals for the months
      April to August from 1999 to 2006. The regression model adjusted for temporal
      trends, weather, and day of the week. Risks were estimated for interquartile
      range increases in the a priori exposure time window of the average of 0-day and
      1-day lagged pollutants. RESULTS: Age was a significant effect modifier for
      hospitalizations, and children age 6 to 18 years consistently had the highest
      risk. Among children age 6 to 18 years, there was a 26% (95% CI, 10% to 44%)
      increased rate of ICU admissions and a 19% increased rate of general
      hospitalizations (95% CI, 12% to 27%) for each 12-microg/m(3) increase in
      PM(2.5). For each 22-ppb increase in ozone, there was a 19% (95% CI, 1% to 40%)
      increased risk for ICU admissions and a 20% (95% CI, 11% to 29%) increased risk
      for general hospitalizations. CONCLUSION: Warm weather patterns of ozone and
      PM(2.5) disproportionately affect children with asthma and appear responsible for
      severe attacks that could have been avoided.

PMID- 20159245
TI  - Predictors of remitting, periodic, and persistent childhood asthma.
AB  - BACKGROUND: The course of mild to moderate persistent asthma in children is not
      clearly established. OBJECTIVE: To determine the rate and predictors for
      remitting, periodic, and persistent asthma in adolescence. METHODS: The Childhood
      Asthma Management Program (CAMP) was a 4.3-year randomized, double-masked,
      multicenter trial in children with mild to moderate persistent asthma that
      compared continuous therapy with either budesonide or nedocromil, each to
      placebo, followed by a 4-year observational follow-up period. Asthma activity
      during the observation period included remitting (no asthma activity in the last
      year), persistent (asthma activity in every quarter), and periodic asthma
      (neither remitting nor persistent). RESULTS: Asthma was identified as remitting
      in 6%, periodic in 39%, and persistent in 55% of the 909 participants, with no
      effect noted from earlier anti-inflammatory treatment during the CAMP trial.
      Within all 3 asthma activity categories, improvements in airway
      hyperresponsiveness, eosinophilia, and asthma morbidity were observed over time.
      Features at entry into CAMP associated with remitting versus persistent asthma
      were lack of allergen sensitization and exposure to indoor allergens (odds ratio
      [OR], 3.23; P < .001), milder asthma (OR, 2.01; P = .03), older age (OR, 1.23; P
      = .01), less airway hyperresponsiveness (higher log methacholine FEV(1) PC(20)
      (OR, 1.39; P = .03), higher prebronchodilator FEV(1) percent predicted (OR, 1.05;
      P = .02), and lower forced vital capacity percent predicted (OR, 0.96; P = .04).
      CONCLUSION: Remission of asthma in adolescence is infrequent and not affected by
      4 years of anti-inflammatory controller therapy. Factors such as sensitization
      and exposure, low lung function, and airway greater hyperresponsiveness decrease
      the likelihood of remitting asthma.

PMID- 20159247
TI  - A randomized placebo-controlled study of intravenous montelukast for the
      treatment of acute asthma.
AB  - BACKGROUND: Current treatments for acute asthma provide inadequate benefit for
      some patients. Intravenous montelukast may complement existent therapies.
      OBJECTIVE: To evaluate efficacy of intravenous montelukast as adjunctive therapy
      for acute asthma. METHODS: A total of 583 adults with acute asthma were treated
      with standard care during a < or = 60-minute screening period. Patients with
      FEV(1) < or =50% predicted were randomly allocated to intravenous montelukast 7
      mg (n = 291) or placebo (n = 292) in addition to standard care. This double-blind
      treatment period lasted until a decision for discharge, hospital admission, or
      discontinuation from the study. The primary efficacy endpoint was the time
      weighted average change in FEV(1) during 60 minutes after drug administration.
      Secondary endpoints included the time-weighted average change in FEV(1) at
      various intervals (10-120 minutes) and percentage of patients with treatment
      failure (defined as hospitalization or lack of decision to discharge by 3 hours
      postadministration). RESULTS: Montelukast significantly increased FEV(1) at 60
      minutes postdose; the difference between change from baseline for placebo (least
      squares mean of 0.22 L; 95% CI, 0.17, 0.27) and montelukast (0.32 L; 95% CI,
      0.27, 0.37) was 0.10 L (95% CI, 0.04, 0.16). Similar improvements in FEV(1)
      related variables were seen at all time points (all P <.05). Although treatment
      failure did not differ between groups (OR 0.92; 95% CI, 0.63, 1.34), a
      prespecified subgroup analysis suggests likely benefit for intravenous
      montelukast at US sites. CONCLUSION: Intravenous montelukast added to standard
      care in adults with acute asthma produced significant relief of airway
      obstruction throughout the 2 hours after administration, with an onset of action
      as early as 10 minutes.

PMID- 20159248
TI  - The evolving role of intravenous leukotriene modifiers in acute asthma.

PMID- 20159249
TI  - Effect of pretreatment with omalizumab on the tolerability of specific
      immunotherapy in allergic asthma.
AB  - BACKGROUND: Although specific immunotherapy is a valuable treatment option for
      patients with allergic asthma, the potential for systemic allergic reactions has
      limited its use, especially for patients with symptomatic disease. OBJECTIVE: To
      evaluate omalizumab's effect on the tolerability of specific immunotherapy in
      patients with symptomatic persistent asthma not adequately controlled with
      inhaled corticosteroids. METHODS: This multicenter, double-blind, parallel-group
      study randomized patients to treatment with omalizumab or placebo, after which
      they received specific immunotherapy to at least 1 of 3 perennial aeroallergens
      (cat, dog, and house dust mite) according to a 4-week, 18-injection cluster
      regimen, followed by 7 weeks of maintenance therapy. The primary efficacy
      variable, a systemic allergic reaction after immunotherapy, was analyzed by using
      the Cochrane-Mantel-Haenszel test. RESULTS: A total of 248 randomized patients
      (126 omalizumab, 122 placebo) received at least 1 dose of immunotherapy and were
      evaluated for efficacy. Patients receiving omalizumab experienced significantly
      fewer systemic allergic reactions to immunotherapy than those receiving placebo
      (17/126 [13.5%] vs 32/122 [26.2%]; P = .017; 95% CI, 2.91% to 22.56%) and had
      fewer respiratory-related (grade 3) systemic allergic reactions (6 vs 24,
      respectively). Grade 4 reactions were reported in 2 patients in each group. More
      omalizumab patients were able to reach the target maintenance immunotherapy dose
      (110 [87.3%] vs 88 [72.1%], respectively; P = .004). CONCLUSION: Use of
      omalizumab in patients whose asthma was symptomatic despite use of inhaled
      corticosteroids was associated with fewer systemic allergic reactions to specific
      immunotherapy and enabled more patients to achieve the target immunotherapy
      maintenance dose.

PMID- 20159250
TI  - Safety of formoterol in patients with asthma: combined analysis of data from
      double-blind, randomized controlled trials.
AB  - BACKGROUND: Concerns exist that regular long-acting beta(2)-adrenergic agonist
      (LABA) therapy may increase the risk of serious asthma-related events. OBJECTIVE:
      To assess risks of formoterol-containing versus non-LABA treatment by using a
      large asthma database. METHODS: This analysis included all blind, parallel-arm,
      randomized, active-controlled and/or placebo-controlled AstraZeneca-sponsored
      asthma studies with formoterol-containing and non-LABA comparator arms. Serious
      adverse events were assessed for inclusion in all-cause death, asthma-related
      death, asthma-related intubation, and asthma-related hospitalization categories
      by using blind adjudication. Data were combined across trials; relative risk (RR)
      was assessed by using Mantel-Haenszel methods. RESULTS: Data were from 13,542
      formoterol-randomized and 9968 non-LABA patients 4 years or older (42 trials), of
      whom 93% and 89%, respectively, received inhaled corticosteroid as part of
      randomized treatment or allowed medication. Incidence of all-cause death was low
      (n=3 and n=4, respectively), with numerically lower all-cause deaths/1000 patient
      treatment years in the formoterol-treated group (0.53) versus the non-LABA group
      (0.82) (RR, 0.64; 95% confidence interval [CI], 0.14-2.92). No asthma-related
      deaths and 1 asthma-related intubation (formoterol-treated group) occurred.
      Asthma-related hospitalizations/1000 patient-treatment years were lower
      numerically in the formoterol-treated group (12.1) versus the non-LABA group
      (16.4) (RR, 0.73; 95% CI, 0.54-1.01), with fewer study discontinuations in the
      formoterol-treated group (12.7% vs 15.4%, respectively; RR, 0.79; 95% CI, 0.74
      0.85). Relative to non-LABA, increasing daily formoterol dose (>/=4.5, 9, 18, 36
      mug) did not increase the rate or incidence of asthma-related hospitalization.
      CONCLUSION: No evidence of increased risk of asthma-related hospitalization, no
      asthma-related deaths, and a low incidence of all-cause death and asthma-related
      intubation were seen with formoterol-containing versus non-LABA treatment.

PMID- 20159251
TI  - Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with
      nasal polyps.
AB  - BACKGROUND: IL-6 activates T(H)17 cells and regulates the response of B
      lymphocytes and regulatory T cells. The IL-6 receptor and the membrane protein,
      glycoprotein 130 (gp130), form an active signaling complex that signals through
      signal transducer and activator of transcription 3 (STAT3) and other signaling
      molecules. Both the IL-6 receptor (IL-6R) and gp130 can be found in soluble forms
      that regulate the pathway. OBJECTIVE: We measured IL-6 signaling components and
      IL-17 in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without
      nasal polyps (CRSsNP), and controls to assess the IL-6 pathway in CRS. METHODS:
      IL-6, soluble IL-6R, soluble gp130 (sgp130), and IL-17 were measured in sinus
      tissue extracts and in nasal lavage fluid by either cytokine bead array or ELISA.
      phosphoSTAT3 (p-STAT3) was determined by Western blot and by
      immunohistochemistry. RESULTS: IL-6 protein was significantly (P < .001)
      increased in CRSwNP compared with CRSsNP and controls. Soluble IL-6R was also
      increased in nasal polyp compared with control tissue (P < .01). Despite elevated
      IL-6 and sIL-6R, IL-17A, E, and F were undetectable in the sinus tissue from most
      of the patients with CRS and controls. p-STAT3 levels were reduced in the polyp
      tissue, possibly indicating reduced activity of IL-6 in the tissue. sgp130 was
      elevated in CRSwNP compared with CRSsNP and controls. CONCLUSION: p-STAT3 levels
      are decreased in CRSwNP despite increased levels of IL-6 and sIL-6R and are
      associated with the absence of an IL-17 response. This may be a response to
      elevated levels of sgp130, a known inhibitor of IL-6 signaling. These results
      indicate that IL-6 and its signaling pathway may be altered in CRSwNP.

PMID- 20159252
TI  - Infant-onset eczema in relation to mental health problems at age 10 years:
      results from a prospective birth cohort study (German Infant Nutrition
      Intervention plus).
AB  - BACKGROUND: Cross-sectional studies suggest an association between eczema and
      mental health problems, but the temporal relationship is unclear. OBJECTIVE: To
      assess the association between infant-onset eczema and mental health problems in
      a prospective study. METHODS: Between 1995 and 1998, a birth cohort study was
      recruited and followed until age 10 years. Physician-diagnosed eczema,
      comorbidities, and a broad set of environmental exposures were assessed at age 1,
      2, 3, 4, 6, and 10 years. First, we investigated the association between infant
      onset eczema (age 1-2 years) and mental health problems at age 10 years according
      to the Strengths and Difficulties Questionnaire. Second, we analyzed the
      likelihood of mental health problems at age 10 years in relation to the course of
      eczema. RESULTS: A total of 2916 infants were eligible for analysis. Compared
      with participants never diagnosed as having eczema, children with infant-onset
      eczema had a significantly increased risk for possible/probable mental health
      problems (Strengths and Difficulties Questionnaire total score) at age 10 years
      (odds ratio, 1.49; 95% CI, 1.13-1.96) and for emotional symptoms (odds ratio,
      1.62; 95% CI, 1.25-2.09). Eczema limited to infancy predicted a significantly
      higher risk for conduct problems at age 10 years. The strength of the association
      between eczema and emotional problems at age 10 years increased with increasing
      eczema persistence. CONCLUSION: Infants with eczema are at increased risk for
      mental health problems at age 10 years. Even if cleared afterward, eczema at age
      1 to 2 years may cause persistent emotional and behavioral difficulties.

PMID- 20159253
TI  - Stimulation of human T cells with sulfonamides and sulfonamide metabolites.
AB  - BACKGROUND: Exposure to sulfonamides is associated with a high incidence of
      hypersensitivity reactions. Antigen-specific T cells are involved in the
      pathogenesis; however, the nature of the antigen interacting with specific T-cell
      receptors is not fully defined. OBJECTIVE: We sought to explore the frequency of
      sulfamethoxazole (SMX)- and SMX metabolite-specific T cells in hypersensitive
      patients, delineate the specificity of clones, define mechanisms of presentation,
      and explore additional reactivity with structurally related sulfonamide
      metabolites. METHODS: SMX- and SMX metabolite-specific T-cell clones were
      generated from 3 patients. Antigen specificity, mechanisms of antigen
      presentation, and cross-reactivity of specific clones were then explored. Low
      lying energy conformations of drugs (metabolites) were modeled, and the energies
      available for protein binding was estimated. RESULTS: Lymphocytes proliferated
      with parent drugs (SMX, sulfadiazine, and sulfapyridine) and both hydroxylamine
      and nitroso metabolites. Three patterns of drug (metabolite) stimulation were
      seen: 44% were SMX metabolite specific, 43% were stimulated with SMX metabolites
      and SMX, and 14% were stimulated with SMX alone. Most metabolite-responsive T
      cells were stimulated with nitroso SMX-modified protein through a hapten
      mechanism involving processing. In contrast to SMX-responsive clones, which were
      highly specific, greater than 50% of nitroso SMX-specific clones were stimulated
      with nitroso metabolites of sulfapyridine and sulfadiazine but not
      nitrosobenzene. Pharmacophore modeling showed that the summation of available
      binding energies for protein interactions and the preferred spatial arrangement
      of atoms in each molecule determine a drug's potential to stimulate specific T
      cells. CONCLUSIONS: Nitroso sulfonamide metabolites form potent antigenic
      determinants for T cells from hypersensitive patients. T-cell responses against
      drugs (metabolites) bound directly to MHC or MHC/peptide complexes can occur
      through cross-reactivity with the haptenic immunogen.

PMID- 20159254
TI  - Voluntarily reported unintentional injections from epinephrine auto-injectors.
AB  - BACKGROUND: Epinephrine auto-injectors provide life-saving prehospital treatment
      for individuals experiencing anaphylaxis in community settings. OBJECTIVE: To
      determine the number, demographics, and associated circumstances and outcomes of
      unintentional injections from epinephrine auto-injectors. METHODS: We searched
      the databases of the American Association of Poison Control Centers and the Food
      and Drug Administration's Safety Information and Adverse Event Report System for
      these incidents as reported by members of the public and by health care
      professionals. RESULTS: From 1994 to 2007, a total of 15,190 unintentional
      injections from epinephrine auto-injectors were reported to US Poison Control
      Centers, 60% of them from 2003 to 2007. Those unintentionally injected had a
      median age of 14 years (interquartile range, 8-35), 55% were female, and 85% were
      injected in a home or other residence. Management was documented in only 4101
      cases (27%), of whom 53% were observed without intervention, 29% were treated,
      13% were neither held for observation nor treated, and 4% refused treatment. In
      contrast, from 1969 to 2007, only 105 unintentional injections from epinephrine
      auto-injectors were reported to MedWatch. Forty percent of these occurred during
      attempts to treat allergic reactions. Injuries resulting in permanent sequelae
      were rarely reported to either US Poison Control Centers or to MedWatch.
      CONCLUSION: The number of reported unintentional injections from epinephrine auto
      injectors increased annually from 1994 to 2007. To prevent these unintentional
      injections, improved epinephrine auto-injector design is needed, along with
      increased vigilance in training the trainers and in training and coaching the
      users, as well as efforts to increase public awareness of the role of epinephrine
      auto-injectors in the first-aid treatment of anaphylaxis in the community.

PMID- 20159255
TI  - Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome.
AB  - BACKGROUND: The hyper-IgE syndrome (HIES) is a primary immunodeficiency
      characterized by infections of the lung and skin, elevated serum IgE, and
      involvement of the soft and bony tissues. Recently, HIES has been associated with
      heterozygous dominant-negative mutations in the signal transducer and activator
      of transcription 3 (STAT3) and severe reductions of T(H)17 cells. OBJECTIVE: To
      determine whether there is a correlation between the genotype and the phenotype
      of patients with HIES and to establish diagnostic criteria to distinguish between
      STAT3 mutated and STAT3 wild-type patients. METHODS: We collected clinical data,
      determined T(H)17 cell numbers, and sequenced STAT3 in 100 patients with a strong
      clinical suspicion of HIES and serum IgE >1000 IU/mL. We explored diagnostic
      criteria by using a machine-learning approach to identify which features best
      predict a STAT3 mutation. RESULTS: In 64 patients, we identified 31 different
      STAT3 mutations, 18 of which were novel. These included mutations at splice sites
      and outside the previously implicated DNA-binding and Src homology 2 domains. A
      combination of 5 clinical features predicted STAT3 mutations with 85% accuracy.
      T(H)17 cells were profoundly reduced in patients harboring STAT3 mutations,
      whereas 10 of 13 patients without mutations had low (<1%) T(H)17 cells but were
      distinct by markedly reduced IFN-gamma-producing CD4(+)T cells. CONCLUSION: We
      propose the following diagnostic guidelines for STAT3-deficient HIES. Possible:
      IgE >1000IU/mL plus a weighted score of clinical features >30 based on recurrent
      pneumonia, newborn rash, pathologic bone fractures, characteristic face, and high
      palate. Probable: These characteristics plus lack of T(H)17 cells or a family
      history for definitive HIES. Definitive: These characteristics plus a dominant
      negative heterozygous mutation in STAT3.

PMID- 20159256
TI  - Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: analysis of
      function and distribution in lymphoid organs.
AB  - BACKGROUND: The Wiskott-Aldrich syndrome (WAS) is a rare genetic disease
      characterized by thrombocytopenia, immunodeficiency, autoimmunity, and
      hematologic malignancies. Secondary mutations leading to re-expression of WAS
      protein (WASP) are relatively frequent in patients with WAS. OBJECTIVE: The
      tissue distribution and function of revertant cells were investigated in a novel
      case of WAS gene secondary mutation. METHODS: A vast combination of approaches
      was used to characterize the second-site mutation, to investigate revertant cell
      function, and to track their distribution over a 18-year clinical follow-up.
      RESULTS: The WAS gene secondary mutation was a 4-nucleotide insertion, 4
      nucleotides downstream of the original deletion. This somatic mutation allowed
      the T-cell-restricted expression of a stable, full-length WASP with a 3-amino
      acid change compared with the wild-type protein. WASP(+) T cells appeared early
      in the spleen (age 10 years) and were highly enriched in a mesenteric lymph node
      at a later time (age 23 years). Revertant T cells had a diversified T-cell
      receptor repertoire and displayed in vitro and in vivo selective advantage. They
      proliferated and produced cytokines normally on T-cell-receptor stimulation.
      Consistently, the revertant WASP correctly localized to the immunologic synapse
      and to the leading edge of migrating T cells. CONCLUSION: Despite the high
      proportion of functional revertant T cells, the patient still has severe
      infections and autoimmune disorders, suggesting that re-expression of WASP in T
      cells is not sufficient to normalize immune functions fully in patients with WAS.

PMID- 20159257
TI  - Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and
      oral antigen-induced anaphylaxis.
AB  - BACKGROUND: The cytokine IL-9 has been implicated in allergic reactions,
      including food allergy, but its contribution to parenteral versus oral antigen
      induced anaphylaxis remains unclear. OBJECTIVES: We sought to delineate the
      contribution of the IL-9/IL-9 receptor alpha-chain (IL-9R) pathway to parenteral
      and oral antigen-induced anaphylaxis. METHODS: Wild-type, IL-9-deficient (Il9(-/
      )), and IL-9R-deficient (Il9R(-/-)) mice were subjected to passive and active
      parenteral and oral antigen (ovalbumin [OVA])-induced anaphylaxis. Severity of
      systemic anaphylaxis was gauged by decreased body temperature; intestinal
      anaphylaxis was assessed based on secretory diarrhea, intestinal mastocytosis,
      and serum murine mast cell protease 1 level. Specific immunoglobulin isotypes or
      immunoglobulin receptor-blocking antibodies were administered before challenge to
      define the role of the IgE and IgG pathways. RESULTS: Repeated oral antigen
      challenge of OVA-sensitized wild-type mice induced anaphylaxis with both systemic
      and intestinal involvement; both were IgE dependent and attenuated in Il9(-/-)
      and Il9R(-/-) mice. In contrast, parenteral OVA challenge of OVA-sensitized wild
      type mice induced systemic anaphylaxis, which was independent of the IL-9/IL-9R
      pathway. Strikingly, the IL-9/IL-9R pathway had no role in either the IgG or IgE
      component of parenteral antigen-induced or anti-IgE and anti-FcgammaRII/III mAb
      induced systemic anaphylaxis. CONCLUSIONS: Parenteral antigen-induced murine
      systemic anaphylaxis is mediated by both IgG- and IgE-dependent pathways, and
      both can occur independently of IL-9/IL-9R signaling. In contrast, oral antigen
      induced intestinal and systemic anaphylaxis is strictly IgE mediated and requires
      IL-9/IL-9R signaling. These studies indicate differential involvement of the IL
      9/IL-9R pathway in systemic and oral antigen-induced anaphylaxis.

PMID- 20159258
TI  - Cysteinyl leukotrienes acting via granule membrane-expressed receptors elicit
      secretion from within cell-free human eosinophil granules.
AB  - BACKGROUND: Cysteinyl leukotrienes (cysLTs) are recognized to act via receptors
      (cysLTRs) expressed on cell surface plasma membranes. Agents that block cysLT(1)
      receptor (cysLT(1)R) are therapeutics for allergic disorders. Eosinophils contain
      multiple preformed proteins stored within their intracellular granules. Cell-free
      eosinophil granules are present extracellularly as intact membrane-bound
      organelles in sites associated with eosinophil infiltration, including asthma,
      rhinitis, and urticaria, but have unknown functional capabilities. OBJECTIVE: We
      evaluated the expression of cysLTRs on eosinophil granule membranes and their
      functional roles in eliciting protein secretion from within eosinophil granules.
      METHODS: We studied secretory responses of human eosinophil granules isolated by
      subcellular fractionation. Granules were stimulated with cysLTs, and eosinophil
      cationic protein and cytokines were measured in the supernatants. Receptor
      expression on granule membranes and eosinophils was evaluated by flow cytometry
      and Western blot. RESULTS: We report that receptors for cysLTs, cysLT(1)R,
      cysLT(2) receptor, and the purinergic P2Y12 receptor, are expressed on eosinophil
      granule membranes. Leukotriene (LT) C(4) and extracellularly generated LTD(4) and
      LTE(4) stimulated isolated eosinophil granules to secrete eosinophil cationic
      protein. MRS 2395, a P2Y12 receptor antagonist, inhibited cysLT-induced
      eosinophil cationic protein release. Montelukast, likely not solely as an
      inhibitor of cysLT(1)R, inhibited eosinophil cationic protein release elicited by
      LTC(4) and LTD(4) as well as by LTE(4). CONCLUSION: These studies identify
      previously unrecognized sites of localization, the membranes of intracellular
      eosinophil granule organelles, and function for cysLT-responsive receptors that
      mediate cysteinyl leukotriene-stimulated secretion from within eosinophil
      granules, including those present extracellularly.

PMID- 20159259
TI  - CD203c expression on human basophils is associated with asthma exacerbation.
AB  - BACKGROUND: CD203c is a basophil cell surface marker used to diagnose and monitor
      various allergic diseases, but its relationship to asthma is not clear.
      OBJECTIVE: We determined whether CD203c expression levels are associated with
      stable and exacerbated asthma. METHODS: We used flow cytometry to compare
      spontaneous expression levels of surface markers on basophils from patients with
      stable or exacerbated asthma and from healthy subjects. Longitudinal changes in
      these expression levels were measured after basophil stimulation by IgE-dependent
      or IgE-independent mechanisms and compared with patients' asthma status. RESULTS:
      Spontaneous expression levels of CD203c were significantly higher on basophils
      from patients with asthma exacerbation than patients with stable asthma or
      healthy subjects. In contrast, no differences in spontaneous expression levels of
      CD63 or CD69 were observed among the 3 groups. Anti-IgE-induced expression of
      CD203c significantly increased in basophils during asthma exacerbation (P =
      .005). Low concentrations of Dermatophagoides pteronyssinus or IL-3 induced
      higher expression levels of CD203c during asthma exacerbation than during
      clinical improvement; induction of CD203c expression by these antigens therefore
      correlates with asthma control. In the patients with clinical improvement, there
      was a correlation between spontaneous CD203c expression levels and the percent
      predicted values of FEV(1) (r = -0.761; P = .022). CONCLUSION: Asthma
      exacerbation was accompanied by increased expression of CD203c on basophils that
      decreased significantly during remission. Basophil expression levels of CD203c
      might therefore be used to monitor asthma in patients.

PMID- 20159260
TI  - Partial improvement of solar urticaria after omalizumab.

PMID- 20159261
TI  - Expression patterns of atopic eczema and respiratory illnesses in a high-risk
      birth cohort.

PMID- 20159262
TI  - Reciprocal interaction of the conjunctiva and cornea in ocular allergy.

PMID- 20159263
TI  - Nasal inflammation in vernal keratoconjunctivitis.

PMID- 20159264
TI  - S2554X mutation in the filaggrin gene is associated with allergen sensitization
      in the Japanese population.

PMID- 20159265
TI  - Genetic predisposition (NLRP3 V198M mutation) for IL-1-mediated inflammation in a
      patient with Schnitzler syndrome.

PMID- 20159266
TI  - Clavulanic acid can be the component in amoxicillin-clavulanic acid responsible
      for immediate hypersensitivity reactions.

PMID- 20159267
TI  - Evaluation of meta-analyses about sublingual immunotherapy in allergic
      respiratory diseases.

PMID- 20159269
TI  - Considerations about the evaluation of the SLIT meta-analyses.

PMID- 20159270
TI  - When oral corticosteroids are essential for persistent severe asthma.

PMID- 20159271
TI  - CAM therapy and vaccine use by U.S. adults: not simply related.

PMID- 20159272
TI  - Fighting the fires of systemic sclerosis.

PMID- 20159273
TI  - Towards more effective emergency contraception?

PMID- 20159274
TI  - Should we dispense with preoperative breast MRI?

PMID- 20159275
TI  - Evidence-based medicine in China.

PMID- 20159276
TI  - Fomenting a prevention revolution for HIV.

PMID- 20159277
TI  - Global health is public health.

PMID- 20159278
TI  - Offline: Long live the King.

PMID- 20159279
TI  - Linda-Gail Bekker: confronting the TB/HIV co-infection epidemic.

PMID- 20159280
TI  - Ventilatory support versus ECMO for severe adult respiratory failure.

PMID- 20159281
TI  - Ventilatory support versus ECMO for severe adult respiratory failure.

PMID- 20159282
TI  - Ventilatory support versus ECMO for severe adult respiratory failure.

PMID- 20159283
TI  - Ventilatory support versus ECMO for severe adult respiratory failure.

PMID- 20159284
TI  - Liraglutide for weight loss in obese people.

PMID- 20159285
TI  - Liraglutide for weight loss in obese people.

PMID- 20159288
TI  - Peptic ulcer disease: further work is required to reduce inequalities.

PMID- 20159291
TI  - Brain death is a scientific concept.

PMID- 20159292
TI  - Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised
      controlled trial.
AB  - BACKGROUND: MRI might improve diagnosis of breast cancer, reducing rates of
      reoperation. We assessed the clinical efficacy of contrast-enhanced MRI in women
      with primary breast cancer. METHODS: We undertook an open, parallel group trial
      in 45 UK centres, with 1623 women aged 18 years or older with biopsy-proven
      primary breast cancer who were scheduled for wide local excision after triple
      assessment. Patients were randomly assigned to receive either MRI (n=816) or no
      further imaging (807), with use of a minimisation algorithm incorporating a
      random element. The primary endpoint was the proportion of patients undergoing a
      repeat operation or further mastectomy within 6 months of random assignment, or a
      pathologically avoidable mastectomy at initial operation. Analysis was by
      intention to treat. This study is registered, ISRCTN number 57474502. FINDINGS:
      816 patients were randomly assigned to MRI and 807 to no MRI. Addition of MRI to
      conventional triple assessment was not significantly associated with reduced a
      reoperation rate, with 153 (19%) needing reoperation in the MRI group versus 156
      (19%) in the no MRI group, (odds ratio 0.96, 95% CI 0.75-1.24; p=0.77).
      INTERPRETATION: Our findings are of benefit to the NHS because they show that MRI
      might be unnecessary in this population of patients to reduce repeat operation
      rates, and could assist in improved use of NHS services. FUNDING: National
      Institute for Health Research's Health Technology Assessment Programme.

PMID- 20159293
TI  - Liver disease in pregnancy.
AB  - Severe liver disease in pregnancy is rare. Pregnancy-related liver disease is the
      most frequent cause of liver dysfunction in pregnancy and provides a real threat
      to fetal and maternal survival. A rapid diagnosis differentiating between liver
      disease related and unrelated to pregnancy is required in women who present with
      liver dysfunction during pregnancy. Research has improved our understanding of
      the pathogenesis of pregnancy-related liver disease, which has translated into
      improved maternal and fetal outcomes. Here, we provide an overview of liver
      diseases that occur in pregnancy, an update on the key mechanisms involved in
      their pathogenesis, and assessment of available treatment options.

PMID- 20159294
TI  - Loss of vision? Clear as crystal!

PMID- 20159301
TI  - 2nd Georgian Bay International Conference on Bioinorganic Chemistry.

PMID- 20159302
TI  - Matrix metalloproteinases.

PMID- 20159303
TI  - Hypopigmented macules.

PMID- 20159304
TI  - Treatment of cellulite: Part I. Pathophysiology.
AB  - Cellulite is a topographic skin change that is nearly ubiquitous in postpubertal
      women. Treatment remains elusive. The various treatments currently available are
      only partially or temporarily effective. Newer therapeutic modalities continue to
      evolve without much understanding of the complex nature of cellulite. The
      successful treatment of cellulite will ultimately depend upon our understanding
      of the pathophysiology of cellulite adipose tissue. Part I of this two-part
      series on cellulite reviews how the concept and perception of cellulite has
      evolved over time and its proposed etiologies. The article also focuses on the
      physiology of human adipose tissue, particularly regarding cellulite.

PMID- 20159305
TI  - Treatment of cellulite: Part II. Advances and controversies.
AB  - Treatments for localized adiposities range from topical creams to liposuction.
      Most treatments lack a substantial proof of efficacy. The unpredictable treatment
      outcome can be related to the fact that cellulite adipose tissue is
      physiologically and biochemically different from subcutaneous tissue found
      elsewhere in the body. Part II of this two-part series on cellulite reviews the
      various treatment options that are currently available for human adipose tissue
      including, but not limited to, cellulite. It also focuses on newer techniques
      that can be potentially useful in the future for the treatment of cellulite.

PMID- 20159306
TI  - 'Relaxers' damage hair: evidence from amino acid analysis.
AB  - BACKGROUND: 'Relaxers' are used by more than two thirds of African females to
      straighten hair, with easy grooming and increased length often cited as reasons.
      A recent study reported relaxed hair lengths much shorter than expected,
      suggesting increased fragility; the potential for scalp inflammation and scarring
      alopecia remains unclear. OBJECTIVE: To investigate the biochemical effects of
      'relaxers' on hair. METHODS: With informed consent, included participants
      represented 3 groups: natural hair, asymptomatic relaxed hair, and symptomatic
      (brittle) relaxed hair. Biochemical analysis was performed by using a Biochrom 30
      amino acid analyzer. Differences in amino acid levels were assessed using either
      Wilcoxon rank sum test or matched-pairs signed-rank test. RESULTS: There was a
      decrease in cystine, citrulline, and arginine; however, an increase in glutamine
      was found in all relaxed compared to natural hair. Cystine levels (milligram per
      gram amino acid nitrogen) were similar in natural proximal and distal hair: 14
      mg/g (range, 4-15 mg/g) versus 14 mg/g (range, 12-15 mg/g); P = .139. In
      asymptomatic relaxed hair, cystine levels were higher in less frequently relaxed
      samples proximal to scalp: 7.5 mg/g (5.6-12) versus 3.3 mg/g (1.3-9.2); P = .005.
      Cystine levels in distal asymptomatic relaxed and symptomatic relaxed hair were
      similar to each other and to those in the genetic hair fragility disease
      trichothiodystrophy. LIMITATIONS: It was not possible to analyze lye and no-lye
      'relaxers' separately. CONCLUSIONS: 'Relaxers' are associated with reduced
      cystine consistent with fragile damaged hair. A decrease in citrulline and
      glutamine has been associated with inflammation; prospective studies are needed
      to investigate whether or how 'relaxers' induce inflammation.

PMID- 20159307
TI  - Commentary: healthy hair and protein loss.

PMID- 20159308
TI  - Long-term follow-up of toenail onychomycosis caused by dermatophytes after
      successful treatment with systemic antifungal agents.
AB  - BACKGROUND: Recurrences (relapse or reinfection) of onychomycosis are not
      uncommon, with percentages reported in various studies ranging from 10% to 53%.
      OBJECTIVE: We sought to determine the prevalence of long-term recurrences of
      toenail onychomycosis caused by dermatophytes cured after systemic antifungal
      treatment with terbinafine (T) or itraconazole (I) and identify risk factors for
      recurrences. METHODS: This 7-year prospective study, started in 2000 and ended in
      2007, included 73 patients periodically followed after successful treatment of
      toenail onychomycosis using either T, 250 mg daily (59 patients), or I, 400 mg
      daily, for 1 week per month (14 patients). Patients were evaluated every 6
      months, with clinical and mycological evaluations being performed. RESULTS:
      Twelve of 73 patients (16.4%) developed a recurrence of onychomycosis a mean time
      of 36 months after successful treatment. These included 5 of the 14 patients
      (35.7%) who had taken I and 7 of the 59 (11.9%) who had taken T (P = .046).
      LIMITATIONS: The number of patients treated with T (59 patients) was more than
      that for I (14 patients). CONCLUSION: The administration of systemic T to treat
      the first episode of onychomycosis may provide better long-term success than I in
      those patients with a complete response. Other factors including the presence of
      predisposing factors, use of nail lacquer as a prophylactic treatment, and the
      dermatophyte strain isolated were not significantly related to relapse.

PMID- 20159309
TI  - Commentary: the illusory tinea unguium cure.

PMID- 20159310
TI  - A randomized, double-blind, placebo-controlled, phase I study of MEDI-545, an
      anti-interferon-alfa monoclonal antibody, in subjects with chronic psoriasis.
AB  - BACKGROUND: Interferon-alfa (IFN-alpha) has been implicated in the pathogenesis
      of psoriasis. OBJECTIVE: To evaluate the safety profile of MEDI-545, a fully
      human anti-IFN-alpha monoclonal antibody and to explore its effect on the
      involvement of type I IFN-alpha activity in the maintenance of established plaque
      psoriasis. METHODS: We conducted an 18-week, randomized, double-blind, placebo
      controlled, dose-escalating study in 36 subjects with chronic plaque psoriasis.
      Subjects received one intravenous dose of MEDI-545 (0.3-30.0 mg/kg) or placebo.
      Study outcomes were safety profile, pharmacokinetics, immunogenicity, and
      clinical effects. RESULTS: There was no difference in adverse events between MEDI
      545 and placebo. Two serious adverse events were reported; one drug-related
      hypotensive infusion reaction occurred in one subject in the 30.0 mg/kg MEDI-545
      dose group, causing discontinuation of study drug in that subject and study
      dismissal of the other subjects in the same cohort; and a myocardial infarction
      occurred in one subject in the 10 mg/kg MEDI-545 dose group, which was considered
      to be unrelated to treatment. MEDI-545 was nonimmunogenic, had a half-life of 21
      days, showed no significant inhibition of the type I IFN gene signature, and had
      no clinical activity. LIMITATIONS: The study addressed only IFN-alpha and chronic
      psoriatic lesions. CONCLUSION: The safety profile of MEDI-545 supports further
      clinical development. IFN-alpha does not appear to be significantly involved in
      the maintenance of established plaque psoriasis.

PMID- 20159311
TI  - A randomized study of the efficacy and safety of injectable poly-L-lactic acid
      versus human-based collagen implant in the treatment of nasolabial fold wrinkles.
AB  - BACKGROUND: Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable,
      biocompatible polymer device. OBJECTIVE: We sought to compare the efficacy and
      safety of injectable PLLA with human-derived collagen in treating nasolabial fold
      wrinkles. METHODS: In this randomized, evaluator-blinded, parallel-group,
      multicenter study, subjects received injectable PLLA (n = 116) or collagen (n =
      117) injections (1-4 visits, 3-week intervals). Wrinkle Assessment Scale scores
      were calculated at screening; posttreatment week 3; months 3, 6, 9, and 13
      (injectable PLLA or collagen groups); and months 19 and 25 (injectable PLLA
      group). Safety data were obtained from subject interviews and case report forms.
      RESULTS: Injectable PLLA significantly improved mean Wrinkle Assessment Scale
      scores (all time points, P < .001). Improvements (up to 25 months after last
      treatment) were significantly greater (P < .001) than with collagen for
      posttreatment months 3 to 13. LIMITATIONS: Mostly white women and subjects with
      Fitzpatrick skin types II and III were included. CONCLUSION: Injectable PLLA
      provides well-tolerated, effective, and long-lasting (up to 25 months) nasolabial
      fold wrinkle correction.

PMID- 20159312
TI  - Epidermotropic Merkel cell carcinoma: a case series with histopathologic
      examination.
AB  - BACKGROUND: Merkel cell carcinoma (MCC), an aggressive malignancy that has been
      increasing in incidence, rarely presents with an epidermotropic pattern.
      OBJECTIVE: We conducted an immunohistochemical evaluation of 6 previously
      unpublished cases of epidermotropic MCC, focusing particularly on the staining
      characteristics of epithelial membrane antigen and cytokeratin-20 in the hope of
      providing insight into the mechanism of epidermotropism in MCC. METHODS: This
      study is a retrospective evaluation using light microscopy and
      immunohistochemistry. RESULTS: Forty cases of MCC with pathology at Rhode Island
      Hospital and the Miriam Hospital in Providence, RI, from 1983 through 2009 were
      reviewed. Following exclusion criteria, 6 patients (5 men, 1 woman) with a mean
      age of 82.5 years (range, 72-92) demonstrated epidermotropism. Three of 6
      patients had MCC of the eyelid. In cases 1, 3, and 6, the perinuclear dot pattern
      observed with cytokeratin-20 in the epidermotropic MCC cells was less pronounced
      than the pattern observed in the dermis, and in all 6 of the tumors, the
      epidermal staining pattern observed with epithelial membrane antigen was not more
      or less prominent than the staining observed in the dermis. LIMITATIONS: The
      small total number of cases of epidermotropic MCC is a limitation. CONCLUSION:
      The data presented reinforce the differential diagnosis of tumors with an
      epidermotropic growth pattern and the importance of immunohistochemical staining
      in the histologic workup of such tumors: squamous cell carcinoma in situ,
      melanoma, mycosis fungoides, eccrine porocarcinoma, sebaceous carcinoma of the
      eyelid, mammary and extramammary Paget disease, MCC, and epidermotropic
      metastases. It is notable that 3 of 6 identified tumors were located on the
      eyelid; further study of epidermotropic MCC may shed more light on this finding,
      either as an unusual coincidence or a finding with unexplained significance.

PMID- 20159313
TI  - The dermal-based borderline melanocytic tumor: a categorical approach.
AB  - BACKGROUND: The borderline melanocytic tumor (BMT) is a morphologically and
      biologically indeterminate melanocytic proliferation manifesting worrisome
      architectural features and cytologic atypia exceeding that encountered in
      melanocytic nevi yet insufficient to warrant designation as melanoma. The
      criteria that define the BMT are not well defined nor is the concept widely
      recognized. OBJECTIVE: The purpose of this study is to provide a practical
      framework for the approach to the dermal BMT. METHODS: Thirty-two patients with
      BMTs extending into the reticular dermis and at a depth of 0.75 mm or more
      underwent local excision and sentinel lymph node biopsy between 2000 and 2006.
      Four categories of BMT were recognized: (1) nevoid BMT (BNM); (2) the atypical
      Spitz tumor (AST); (3) pigmented epithelioid melanocytoma (PEM); and (4) BMT
      arising in a deep penetrating nevus (B-DPN). RESULTS: Four patients were in the
      BNM category (male/female ratio [M:F] = 1:3; mean age = 27 years, range = 15-36),
      14 in the AST category (M:F = 7:7; mean age = 20.9, range = 3-58), 7 in the PEM
      category (M:F = 4:3; mean age = 23.5, range = 3-39), and 7 in the B-DPN category
      (M:F = 5:2; mean age = 22.3, range = 14-36). The percentages of patients with
      positive sentinel nodes in each category were 25% (1/4), 35% (5/14), 14% (1/7),
      and 57% (4/7), respectively. The average time of follow-up was approximately 4.2
      years. One patient, a 36-year-old man, died of disease, while the others are
      alive and well. In the one death attributable to widespread metastatic disease,
      the lesion was initially interpreted as a deep penetrating nevus; however,
      retrospective review revealed features compatible with a B-DPN; the review was
      prompted by a recurrence that was morphologically compatible with a Clark level V
      malignant melanoma, reflecting clinical and morphologic progression. LIMITATIONS:
      The mean follow-up was less than 5 years. Molecular studies to further explore
      the biologic commonality with melanoma were not performed. CONCLUSION: The dermal
      variant of BMT is a tumor of younger adults and children that can be associated
      with lymph node disease and a potential for morphologic and biologic progression
      when inadequately treated.

PMID- 20159314
TI  - Hormone therapy for acne.

PMID- 20159315
TI  - Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated
      temperature (CANDLE) syndrome.
AB  - Several syndromes manifest as recurrent daily fevers, skin lesions, and
      multisystem inflammation. We describe 4 patients with early-onset recurrent
      fevers, annular violaceous plaques, persistent violaceous eyelid swelling, low
      weight and height, lipodystrophy, hepatomegaly, and a range of visceral
      inflammatory manifestations. Laboratory abnormalities included chronic anemia,
      elevated acute-phase reactants, and raised liver enzymes. Histopathologic
      examination of lesional skin showed atypical mononuclear infiltrates of myeloid
      lineage and mature neutrophils. Our patients have a distinctive early-onset,
      chronic inflammatory condition with atypical or immature myeloid infiltrates in
      the skin. We propose the acronym CANDLE (chronic atypical neutrophilic dermatosis
      with lipodystrophy and elevated temperature) syndrome for this newly described
      disorder, which is probably genetic in origin.

PMID- 20159316
TI  - Grooming and central centrifugal cicatricial alopecia.

PMID- 20159317
TI  - Cutaneous leishmaniasis in Texas.

PMID- 20159318
TI  - Goeckerman treatment: neglected in the consensus approach for critically
      challenging case scenarios in moderate to severe psoriasis.

PMID- 20159319
TI  - Dermatitis herpetiformis exacerbated by cornstarch.

PMID- 20159320
TI  - Decrease of ultraviolet A light-induced "common deletion" in healthy volunteers
      after oral Polypodium leucotomos extract supplement in a randomized clinical
      trial.

PMID- 20159321
TI  - Interobserver accuracy of store and forward teledermatology for skin neoplasms.

PMID- 20159322
TI  - Goeckerman therapy versus biologics in the treatment of psoriasis.

PMID- 20159323
TI  - Hypnosis in refractory alopecia areata significantly improves depression,
      anxiety, and life quality but not hair regrowth.

PMID- 20159324
TI  - Dermatology inpatient consultations: a retrospective study.

PMID- 20159325
TI  - Mineral make-up and its potential utility in patients with contact dermatitis.

PMID- 20159326
TI  - Where did current academic dermatologists train?

PMID- 20159327
TI  - Xanthogranuloma on the penis of an adult: an unusual localization.

PMID- 20159328
TI  - Concordance rate of alopecia areata in identical twins supports both genetic and
      environmental factors.

PMID- 20159329
TI  - Acanthosis nigricans in a patient with sarcoma of unknown origin.

PMID- 20159330
TI  - Unilateral nevoid telangiectasia on the lower extremity of a pediatric patient.

PMID- 20159331
TI  - Acral lymphomatoid papulosis.

PMID- 20159332
TI  - Cetuximab-induced hypertrichosis of the scalp and eyelashes.

PMID- 20159333
TI  - JAAD grand rounds quiz. Scalp abscesses, fluctuant nodules, and patchy alopecia
      in an African American male.

PMID- 20159334
TI  - JAAD grand rounds quiz. Patchy alopecia following chemotherapy.

PMID- 20159335
TI  - JAAD grand rounds quiz. Linear scalp plaques.

PMID- 20159336
TI  - Preface: Promises kept: robust discovery in psychiatric genetics.

PMID- 20159338
TI  - Methods: genetic epidemiology.
AB  - Given the potential benefits of gene identification in psychiatry, genetic
      epidemiology has become a mainstream discipline within the field. This article
      discusses the main tools for gene discovery. The focus is on the designs and
      analytic approaches for each of these methods. Because most gene discovery has
      now moved to genetic association studies, and most recently to genome-wide
      association studies, the focus is on methods for this design. Also highlighted
      are the current challenges of genetic epidemiology as a prelude to future
      approaches that may be applied to psychiatric disorders in the coming years.

PMID- 20159337
TI  - Genetics of psychiatric disorders methods: molecular approaches.
AB  - The practice of psychiatry has long suffered from the limited information
      available on the biological basis of mental disorders. This limitation is now
      coming to an end. Advances in DNA analysis technologies and in our understanding
      of the human genome, together with our new knowledge of the properties of the
      genome and significant efforts toward generating large patient and control sample
      collections, have paved the way for successful genome-wide association studies.
      As a result, reports now appear in the literature every week identifying new
      genes for complex disorders. Next-generation sequencing methods, combined with
      the results of association and perhaps linkage studies, will help us uncover
      missing heritability factors, achieve a better understanding of the genetic
      aspects of psychiatric disease, and devise the best strategies for incorporating
      genetics in the service of patients.

PMID- 20159339
TI  - The role of genetics in the etiology of schizophrenia.
AB  - Schizophrenia is a complex genetic disorder manifesting combined environmental
      and genetic causation. Recently, genome-wide association experiments yielded
      remarkable new experimental evidence that is leading to a better understanding of
      the genetic models and the biological risk factors involved in schizophrenia.
      These studies have discovered uncommon copy number variations (mainly deletions)
      and common single nucleotide polymorphisms with alleles associated with
      schizophrenia. The aggregate data provide support for polygenic inheritance and
      for genetic overlap of schizophrenia with autism and with bipolar disorder. It is
      anticipated that the application of a myriad of tools from systems biology, in
      combination with biological functional experiments, will lead to a delineation of
      biological pathways involved in the pathophysiology of schizophrenia, and
      eventually to new therapies.

PMID- 20159340
TI  - Genetic research into bipolar disorder: the need for a research framework that
      integrates sophisticated molecular biology and clinically informed phenotype
      characterization.
AB  - Research into the genetic basis of bipolar disorder (BD) has reached a turning
      point. Genome-wide association studies (GWAS), encompassing several thousand
      samples, have produced replicated evidence for some novel susceptibility genes;
      however, the genetic variants implicated so far account for only a fraction of
      disease liability, a phenomenon not limited to psychiatric phenotypes but
      characteristic of all complex genetic traits studied to date. It appears that
      pure genomic approaches, such as GWAS alone, will not suffice to unravel the
      genetic basis of a complex illness like BD. Genomic approaches will need to be
      complemented by a variety of strategies, including phenomics, epigenomics,
      pharmacogenomics, and neurobiology, as well as the study of environmental
      factors. This review highlights the most promising findings from recent GWAS and
      candidate gene studies in BD. It furthermore sketches out a potential research
      framework integrating various lines of research into the molecular biological
      basis of BD.

PMID- 20159341
TI  - The genetics of autism: key issues, recent findings, and clinical implications.
AB  - Autism spectrum disorders (ASDs) are highly heritable. Gene discovery promises to
      help illuminate the pathophysiology of these syndromes, yielding opportunities
      for the development of novel treatments and understanding of their natural
      history. Although the underlying genetic architecture of ASDs is not yet known,
      the literature demonstrates that it is not a monogenic disorder with mendelian
      inheritance, rather a group of complex genetic syndromes with risk deriving from
      genetic variations in multiple genes. This article reviews the origins of the
      common versus rare variant debate, highlights recent findings in the field, and
      addresses the clinical implications of common and rare variant discoveries.

PMID- 20159342
TI  - Genetics of addictions.
AB  - Addictions include a group of common, heritable psychiatric illnesses that have
      multiple psychiatric and medical comorbidities. Robust genetic associations have
      been found for alcohol dependence, nicotine dependence, and cocaine dependence.
      Common genetic associations have been found between alcohol dependence and
      aerodigestive cancers and between nicotine dependence and lung disease. These
      associations highlight the importance of understanding the genetics of substance
      dependence in the context of its multiple medical and psychiatric comorbidities.

PMID- 20159343
TI  - The genetics of major depression: moving beyond the monoamine hypothesis.
AB  - Efforts to unlock the biology of major depressive disorder (MDD) are proceeding
      on multiple fronts. In this article, the authors review the current understanding
      of epidemiological evidence for a heritable component to MDD risk, as well as
      recent advances in linkage, candidate gene, and genome-wide association analyses
      of MDD and related disease subtypes and endophenotypes. While monoamine signaling
      has preoccupied the bulk of scientific investigation to date, nontraditional gene
      candidates such as PCLO and GRM7 are now emerging and beginning to change the
      landscape for future human and animal research on depression.

PMID- 20159344
TI  - Genetics of obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder is a common debilitating condition affecting
      individuals from childhood through adult life. There is good evidence of genetic
      contribution to its etiology, but environmental risk factors also are likely to
      be involved. The condition probably has a complex pattern of inheritance.
      Molecular studies have identified several potentially relevant genes, but much
      additional research is needed to establish definitive causes of the condition.

PMID- 20159345
TI  - Molecular genetics of attention deficit hyperactivity disorder.
AB  - Although twin studies demonstrate that ADHD is a highly heritable condition,
      molecular genetic studies suggest that the genetic architecture of ADHD is
      complex. The handful of genome-wide linkage and association scans that have been
      conducted thus far show divergent findings and are, therefore, not conclusive.
      Similarly, many of the candidate genes reviewed here (ie, DBH, MAOA, SLC6A2, TPH
      2, SLC6A4, CHRNA4, GRIN2A) are theoretically compelling from neurobiological
      systems perspective but available data are sparse and inconsistent. However,
      candidate gene studies of ADHD have produced substantial evidence implicating
      several genes in the etiology of the disorder, with meta-analyses supportive of a
      role of the genes coding for DRD4, DRD5, SLC6A3, SNAP-25, and HTR1B in the
      etiology of ADHD.

PMID- 20159347
TI  - Predictive and diagnostic genetic testing in psychiatry.
AB  - The recent advent of commercially available genetic tests for the diagnosis of
      several mental illnesses has led to intense controversy amongst the psychiatric
      research community. In this article the authors review these developments, and
      contrast these with the growing evidence from genome-wide association studies
      that highly heritable psychiatric conditions such as schizophrenia are due to the
      contributions and interaction of multiple allelic variants, each of small effect
      size. There is also evidence for the contribution of some highly penetrant rare
      de novo copy number variants, though the lack of disease specificity for these is
      of concern. This article outlines the prerequisites for predictive and diagnostic
      genetic tests, such as clinical validity and utility, and reviews the opportunity
      that genetic tests for mental illnesses present. As the scientific discourse on
      genetic tests for complex disorders is not limited to psychiatry, the authors
      outline current thoughts on the significance of genome-wide association studies
      across health, and the phenomenon of direct-to-consumer tests in medicine. The
      attitudes and understanding of patients, families, and clinicians about the
      future (currently hypothetical) scenario of psychiatric genetic tests are
      discussed, as is the potential for such testing to increase, rather than diminish
      stigma. Finally, recommendations on the future development and availability of
      genetic tests in psychiatry are provided.

PMID- 20159348
TI  - It is all about relationships.

PMID- 20159349
TI  - Evaluating the relationship between inattention and impulsivity-related falls in
      hospitalized older adults.
AB  - Impulsivity in older adults is poorly understood and there is limited literature
      on the relationship between impulsivity and falls. This retrospective study
      evaluated the relationship between of inattention and impulsivity related falls
      (IRF) in hospitalized older adults. The sample (N = 192) included patients 65
      years and older with a documented in-patient fall in 2007. "Impaired judgment"
      was identified as the critical attribute of IRF. The Confusion Assessment Method
      item for inattention was extracted as the variable for inattention. Twenty-eight
      percent (28%) of falls were classified as IRF. A significant relationship was
      found between inattention on the shift prior to a fall and the fall being an IRF
      (Chi-square = 45.5, df = 1, p = .00, Phi = .54, p = .00). Early identification of
      older adults with impaired attention has potential to reduce IRF when nursing
      uses this assessment to implement additional safety interventions for
      hospitalized older adults.

PMID- 20159350
TI  - More than a prescriber: gerontological nurse practitioners' perspectives on
      prescribing and pharmaceutical marketing.
AB  - The purpose of this study was to gain understanding about nurse practitioners'
      (NPs') prescriptive decision making for geriatric patients with attention to
      pharmaceutical marketing influences. Prior research has focused on physician
      prescribers and identified suboptimal practices. Because the majority of
      medications are prescribed to older adults, NPs in geriatric practice were
      targeted as an information-rich group to interview about prescribing issues.
      Given the exploratory nature of this research, qualitative focus group methods
      were employed using content analysis. Fifteen NPs were recruited at an annual
      national geriatric NP conference. They worked in all regions of the United
      States, had an average of 9 years prescribing experience, and participated in 1
      of the 2 focus groups. The key theme that emerged was that they were more than a
      prescriber. Findings revealed overwhelming consistency among the NP participants
      that their nursing background instilled a holistic approach that encompassed both
      nondrug and therapeutic drug options and skepticism about drug marketing, as well
      as offered a positive difference by tailoring to their patients' biophysical,
      psychological, and economic needs with an involvement in the interplay of
      geriatric care issues not typically addressed by physicians. The participants'
      reported approaches were in alignment with geriatric prescribing recommendations.

PMID- 20159351
TI  - Antithrombosis management in community-dwelling elderly: improving safety.
AB  - Thrombus-related conditions are increasing in the elderly population. This
      article provides an overview of thrombus formation and describes the various
      pharmacologic options for prevention. Thromboprophylaxis requires an assessment
      of the risks and benefits of treatment so that catastrophic bleeding does not
      result. A practice model, the "S.A.F.E. Triad" is proposed to provide a framework
      for addressing safety concerns, while algorithms assist with decision-making.

PMID- 20159352
TI  - Perceived benefits of meditative movement in older adults.
AB  - Several meditative movement interventions have been designed for older adults in
      the community setting. Previous reviews have reported on the objective efficacy
      of interventions, but little has been reported on the effectiveness of such
      interventions. The purpose of this review is to report the perceived psychosocial
      benefits and health outcomes of meditative movement such as Tai chi (TC) and
      Qigong to inform clinicians on what interventions "work" under what conditions
      and for whom. Thirty seven studies were included in this review and were
      synthesized with three content areas: perceived improved outcomes and mediators;
      and perceived factors for initiating TC. The 37 studies included 1856
      participants (mean age 67.76) who were mostly women (n=1435) and white (n=808).
      Some were Taiwanese (n=117), non-white (n=72), Chinese (n=39) and African
      American (n=28) and the studies were conducted in 9 countries. Clinicians can use
      the findings of this review to identify motivational factors for initiation and
      adherence and identify specific benefits from an effective TC intervention.

PMID- 20159353
TI  - Trick or TREAT? More condemning evidence against ESAs.

PMID- 20159354
TI  - Legislative/Legal update--what's new in Washington for geriatric nursing care.

PMID- 20159355
TI  - Storytelling.
AB  - Storytelling can be therapeutic. For the person, it is both validating and
      valuing--as nothing else can do. There is a connection between old age and
      spirituality and a quest for transcendence--to express one's self as part of the
      human condition. This article seeks to describe the links among spirituality,
      nursing care, and patient/resident storytelling, and includes suggestions on how
      to help older adults tell their stories, even if they are cognitively challenged
      by memory and language loss. It describes a worldview as expressed in several of
      the new nursing theories as "humanness": a life cycle of continuous growth
      leading, perhaps, to "self-transcendence." Storytelling can be peacemaking and
      transformative. The voice of the "wounded storyteller" and how nurses can make
      that voice heard might be the takeaway message.

PMID- 20159356
TI  - Individualized care for frail older adults: challenges for health care reform in
      acute and critical care.

PMID- 20159346
TI  - The promise and reality of pharmacogenetics in psychiatry.
AB  - Existing psychotropic medications for the treatment of mental illnesses,
      including antidepressants, mood stabilizers, and antipsychotics, are clinically
      suboptimal. They are effective in only a subset of patients or produce partial
      responses, and they are often associated with debilitating side effects that
      discourage adherence. There is growing enthusiasm in the promise of
      pharmacogenetics to personalize the use of these treatments to maximize their
      efficacy and tolerability; however, there is still a long way to go before this
      promise becomes a reality. This article reviews the progress that has been made
      in research toward understanding how genetic factors influence psychotropic drug
      responses and the challenges that lie ahead in translating the research findings
      into clinical practices that yield tangible benefits for patients with mental
      illnesses.

PMID- 20159357
TI  - Timing of drug administration during CPR and the role of simulation.

PMID- 20159358
TI  - American society for radiation oncology intersociety summit summary.

PMID- 20159359
TI  - Radiation oncology in undergraduate medical education: a literature review.
AB  - PURPOSE: To review the published literature pertaining to radiation oncology in
      undergraduate medical education. METHODS AND MATERIALS: Ovid MEDLINE, Ovid
      MEDLINE Daily Update and EMBASE databases were searched for the 11-year period of
      January 1, 1998, through the last week of March 2009. A medical librarian used an
      extensive list of indexed subject headings and text words. RESULTS: The search
      returned 640 article references, but only seven contained significant information
      pertaining to teaching radiation oncology to medical undergraduates. One article
      described a comprehensive oncology curriculum including recommended radiation
      oncology teaching objectives and sample student evaluations, two described
      integrating radiation oncology teaching into a radiology rotation, two described
      multidisciplinary anatomy-based courses intended to reinforce principles of tumor
      biology and radiotherapy planning, one described an exercise designed to test
      clinical reasoning skills within radiation oncology cases, and one described a
      Web-based curriculum involving oncologic physics. CONCLUSIONS: To the authors'
      knowledge, this is the first review of the literature pertaining to teaching
      radiation oncology to medical undergraduates, and it demonstrates the paucity of
      published work in this area of medical education. Teaching radiation oncology
      should begin early in the undergraduate process, should be mandatory for all
      students, and should impart knowledge relevant to future general practitioners
      rather than detailed information relevant only to oncologists. Educators should
      make use of available model curricula and should integrate radiation oncology
      teaching into existing curricula or construct stand-alone oncology rotations
      where the principles of radiation oncology can be conveyed. Assessments of
      student knowledge and curriculum effectiveness are critical.

PMID- 20159361
TI  - Current management of primary central nervous system lymphoma.
AB  - Primary central nervous cell lymphoma (PCNSL) is an uncommon neoplasm of the
      brain, leptomeninges, and rarely the spinal cord. Initially thought to be
      characteristically associated with congenital, iatrogenic, or acquired
      immunosuppression, PCNSL is now recognized with increasing frequency in
      immunocompetent individuals. The role of surgery is limited to establishing
      diagnosis, as PCNSL is often multifocal with a propensity to involve the
      subarachnoid space. A whole-brain radiation volume has empirically been used to
      adequately address the multifocal tumor frequently encountered at the time of
      PCNSL diagnosis. Despite high rates of response after whole-brain radiotherapy
      (WBRT), rapid recurrence is common and long-term survival is the exception.
      Chemotherapy alone or in combination with WBRT has more recently become the
      treatment of choice. Most effective regimens contain high-dose methotrexate and
      or other agents that are capable of penetrating the blood-brain barrier. High
      response rates and improved survival with the use of chemotherapy has led to
      treatment strategies that defer or eliminate WBRT in hopes of lessening the risk
      of neurotoxicity attributed to WBRT. Unfortunately, elimination of WBRT is also
      associated with a higher rate of relapse. Combined chemotherapy and WBRT regimens
      are now being explored that use lower total doses of radiation and altered
      fractionation schedules with the aim of maintaining high rates of tumor control
      while minimizing neurotoxicity. Pretreatment, multifactor prognostic indices have
      recently been described that may allow selection of treatment regimens that
      strike an appropriate balance of risk and benefit for the individual PCNSL
      patient.

PMID- 20159360
TI  - Radiation-related heart disease: current knowledge and future prospects.

PMID- 20159362
TI  - Development of hypoxia in a preclinical model of tumor micrometastases.
AB  - PURPOSE: Hypoxic regions have been shown to be a characteristic feature of a wide
      variety of human primary tumors, whereas the oxygenation status of subclinical
      micrometastases is in general unknown. The development of hypoxia in a xenograft
      model of microscopic metastases was investigated in this study. METHODS AND
      MATERIALS: U-25-GFP human melanomas growing in dorsal window chamber preparations
      in BALB/c nu/nu mice were used as a preclinical model of micrometastases. Tumor
      blood supply time and morphologic parameters of the vascular network were
      determined from first-pass imaging movies and vascular maps recorded by use of
      155-kDa tetramethylrhodamine isothiocyanate-labeled dextran as a vascular tracer.
      Tumor hypoxia was assessed from immunohistochemical preparations of the imaged
      tissue by use of pimonidazole as a hypoxia marker. RESULTS: Nearly half of the
      tumors had developed hypoxic regions when they reached a diameter of 2 to 3 mm.
      Tumors with multiple hypoxic foci showed a low growth rate, low blood flow
      velocity, high vessel tortuosity, high vessel segment length, and high vascular
      density, whereas tumors with a single hypoxic region showed a high growth rate,
      high blood flow velocity, low vessel tortuosity, low vessel segment length, and
      low vascular density. The tumors with hypoxic regions did not differ from those
      without hypoxia in any single parameter. CONCLUSIONS: U-25-GFP xenograft models
      of vascularized human tumor micrometastases may develop hypoxic regions as a
      consequence of two distinctly different morphologic abnormalities in the vascular
      network: high resistance against blood flow (i.e., high vessel tortuosity and
      high vessel segment length) or low vascular density.

PMID- 20159363
TI  - Differential radiosensitizing effect of valproic acid in differentiation versus
      self-renewal promoting culture conditions.
AB  - PURPOSE: It has been shown that valproic acid (VA) enhances the proliferation and
      self-renewal of normal hematopoietic stem cells and that breast cancer
      stem/progenitor cells can be resistant to radiation. From these data, we
      hypothesized that VA would fail to radiosensitize breast cancer stem/progenitor
      cells grown to three-dimensional (3D) mammospheres. METHODS AND MATERIALS: We
      used the MCF7 breast cancer cell line grown under stem cell-promoting culture
      conditions (3D mammosphere) and standard nonstem cell monolayer culture
      conditions (two-dimensional) to examine the effect of pretreatment with VA on
      radiation sensitivity in clonogenic survival assays and on the expression of
      embryonic stem cell transcription factors. RESULTS: 3D-cultured MCF-7 cells
      expressed higher levels of Oct4, Nanog, and Sox2. The 3D passage enriched self
      renewal and increased radioresistance in the 3D mammosphere formation assays. VA
      radiosensitized adherent cells but radioprotected 3D cells in single-fraction
      clonogenic assays. Moreover, fractionated radiation sensitized VA-treated
      adherent MCF7 cells but did not have a significant effect on VA-treated single
      cells grown to mammospheres. CONCLUSION: We have concluded that VA might
      preferentially radiosensitize differentiated cells compared with those expressing
      stem cell surrogates and that stem cell-promoting culture is a useful tool for in
      vitro evaluation of novel cancer therapeutic agents and radiosensitizers.

PMID- 20159364
TI  - Prostate-specific natural health products (dietary supplements) radiosensitize
      normal prostate cells.
AB  - PURPOSE: Prostate-specific health products (dietary supplements) are taken by
      cancer patients to alleviate the symptoms linked with poor prostate health.
      However, the effect of these agents on evidence-based radiotherapy practice is
      poorly understood. The present study aimed to determine whether dietary
      supplements radiosensitized normal prostate or prostate cancer cell lines.
      METHODS AND MATERIALS: Three well-known prostate-specific dietary supplements
      were purchased from commercial sources available to patients (Trinovin, Provelex,
      and Prostate Rx). The cells used in the study included normal prostate lines
      (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal
      nonprostate line (HaCaT). Supplement toxicity was assessed using cell
      proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5
      4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium
      iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and
      DNA repair by assessing gammaH2AX. RESULTS: The cell growth and radiosensitivity
      of the malignant PC3, DU145, and LNcaP cells were not affected by any of the
      dietary prostate supplements (Provelex [2 microg/mL], Trinovin [10 microg/mL],
      and Prostate Rx [50 microg/mL]). However, both Trinovin (10 microg/mL) and
      Prostate Rx (6 microg/mL) inhibited the growth rate of the normal prostate cell
      lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through
      the inhibition of DNA repair. CONCLUSION: The use of prostate-specific dietary
      supplements should be discouraged during radiotherapy owing to the preferential
      radiosensitization of normal prostate cells.

PMID- 20159365
TI  - Azidothymidine enhances fluorodeoxyuridine-mediated radiosensitization.
AB  - PURPOSE: To examine the role of DNA repair and altered thymidine analogues in
      altering the response to radiation during thymidine deprivation. METHODS AND
      MATERIALS: Mismatch repair-deficient and -proficient cell lines HEC59 and HC-2.4
      were treated with fluorodeoxyuridine (FUdR), azidothymidine (AZT), and
      irradiation either alone or in combination, and outcomes of clonogenic survival
      and cell-cycle distributions were determined. RESULTS: Survival outcomes for all
      treatments were similar for both cell lines, suggesting that hMSH2 does not
      significantly influence thymidine deprivation toxicity or radiosensitization. The
      chain-terminating thymidine analogue AZT increased the toxicity of FUdR and
      increased DNA fragmentation. The combination of FUdR and AZT afforded greater
      radiosensitization than either drug alone. Drug enhancement ratios, the degree of
      excess radiation-induced cell death in drug-treated cultures compared with
      radiation alone for HEC59, were 1.2, 1.4, and 1.8 for AZT, FUdR, and the
      combination, respectively. Enhancement ratios for HC-2.4 were 1.3, 1.5, and 1.8
      for AZT, FUdR, and the combination, respectively. CONCLUSION: Azidothymidine, a
      chain-terminating thymidine analogue, can enhance the radiosensitizing affects of
      thymidine deprivation. Deoxyribonucleic acid strand breaks may play an important
      role in the mechanism of thymidine deprivation-induced radiosensitization.

PMID- 20159366
TI  - Equivalence in dose fall-off for isocentric and nonisocentric intracranial
      treatment modalities and its impact on dose fractionation schemes.
AB  - PURPOSE: To investigate whether dose fall-off characteristics would be
      significantly different among intracranial radiosurgery modalities and the
      influence of these characteristics on fractionation schemes in terms of normal
      tissue sparing. METHODS AND MATERIALS: An analytic model was developed to measure
      dose fall-off characteristics near the target independent of treatment
      modalities. Variations in the peripheral dose fall-off characteristics were then
      examined and compared for intracranial tumors treated with Gamma Knife,
      Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective
      dose (EUBED) for the normal brain tissue was calculated. Functional dependence of
      the normal brain EUBED on varying numbers of fractions (1 to 30) was studied for
      the three modalities. RESULTS: The derived model fitted remarkably well for all
      the cases (R(2) > 0.99). No statistically significant differences in the dose
      fall-off relationships were found between the three modalities. Based on the
      extent of variations in the dose fall-off curves, normal brain EUBED was found to
      decrease with increasing number of fractions for the targets, with alpha/beta
      ranging from 10 to 20. This decrease was most pronounced for hypofractionated
      treatments with fewer than 10 fractions. Additionally, EUBED was found to
      increase slightly with increasing number of fractions for targets with alpha/beta
      ranging from 2 to 5. CONCLUSION: Nearly identical dose fall-off characteristics
      were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED
      calculations, normal brain sparing was found to favor hypofractionated treatments
      for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction
      treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.

PMID- 20159367
TI  - A mixed-modality 3d-conformal accelerated partial breast irradiation technique
      using opposed mini-tangent photon fields and en face electrons to minimize the
      lung exposure to radiation: in regard to Jain et al. (Int J Radiat Oncol Biol
      Phys 2009;75:82-88).

PMID- 20159368
TI  - Comment on Drs. Withers and Peters' letter concerning the editorial "magical
      protons?".

PMID- 20159371
TI  - Tumor hypoxia as a function of hemoglobin concentration and tumor perfusion.

PMID- 20159373
TI  - Sequential changes of Legionella antigens and bacterial load in the lungs and
      urines of a mouse model of pneumonia.
AB  - Legionella pneumophila is an important cause of community- and hospital-acquired
      pneumonia. In spite of the introduction of the urinary antigen detection method,
      Legionella pneumonia may be still underdiagnosed. We performed kinetic and
      quantitative analysis of diagnostic markers, such as bacterial loads, DNA assays,
      and antigen titers, in a 28-day time course murine model of L. pneumophila
      pneumonia. L. pneumophila replicated approximately 100-fold in the lungs of A/J
      mice in the first 48 h, and then became undetectable on day 14. Unexpectedly,
      pathogens other than L. pneumophila were consistently recovered from the lungs
      and livers at the acute phases, although those numbers were far below Legionella
      loads in the lungs. The peaks of specific antigen titer were observed on 48 h in
      the lungs, bronchoalveolar lavage (BAL) fluids, and urines and sustained positive
      even at 28 days after the infection. Especially, the lung homogenates and BAL
      fluids demonstrated 16 to 64 times higher levels of antigen titer than the urines
      by the end of observation. Legionella-specific DNA in the lungs was detected by
      polymerase chain reaction and loop-mediated isothermal amplification methods
      until 7 and 14 days after the infection, respectively. The inflammatory
      cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin 6, and MIP-2,
      exhibited a peak on the acute phase, whereas the maximal production of high
      mobility group box 1 in the serum was observed on day 7. These results
      characterized the kinetic nature of diagnostic markers in L. pneumophila
      pneumonia. The present data suggested prolonged and compartmentalized deposition
      of antigen in the lungs, which may have an impact on the diagnosis of L.
      pneumophila pneumonia, especially in missed cases even after recovery from
      disease.

PMID- 20159374
TI  - Detection of Histoplasma capsulatum DNA in human samples by real-time polymerase
      chain reaction.
AB  - The main aim of our study was to determine the added value of real-time
      polymerase chain reaction (PCR) for the diagnosis of Histoplasma capsulatum in
      routine biologic practice. No amplification signal was observed with the 18 non
      H. capsulatum strains used to test the specificity of the protocol. The
      sensitivity threshold of the real-time PCR assay was about 10 fg of H. capsulatum
      DNA per microliter, tested with a 10-fold serial dilution of the positive
      control. We analyzed 348 human samples submitted for the routine diagnosis of
      systemic mycosis. Real-time PCR using the TaqMan system was evaluated against
      direct microscopic examination and culture. Among the 341 samples without PCR
      inhibition (n = 7), 66 tested positive by culture, whereas 74 tested positive by
      real-time PCR. Sensitivity of the real-time PCR assay was estimated at 95.4% and
      specificity at 96.0% with respect to culture, widely considered to be the gold
      standard method; however, the molecular approach in fact produced better
      sensitivity and specificity results. Moreover, for the 38 samples that tested
      negative by direct examination but positive by culture, the culture method took a
      mean of 31 days longer than the PCR method to generate results. The protocol
      presented here may be very useful for improving routine histoplasmosis diagnosis.

PMID- 20159375
TI  - Lichtheimia hongkongensis sp. nov., a novel Lichtheimia spp. associated with
      rhinocerebral, gastrointestinal, and cutaneous mucormycosis.
AB  - Three thermotolerant "Absidia-like" isolates with unique morphologic
      characteristics, recovered from nasopharyngeal swab of a liver transplant
      recipient, gastric biopsy of a renal transplant recipient, and skin biopsy of a
      man with burn, respectively, were characterized. Microscopic examination showed
      nonseptate hyphae with highly branched sporangiophores. Uniquely, most side
      branches were circinate, and abundant pleomorphic giant cells with fingerlike
      projections were observed, characteristics absent from other Absidia/Lichtheimia
      spp. ITS1-5.8S-ITS2 rRNA gene cluster, partial EF1alpha gene, and partial beta
      actin gene sequencing showed that the 3 strains formed a distinct cluster, most
      closely related to, but distinct from, Lichtheimia corymbifera, Lichtheimia
      blakesleeana, and Lichtheimia hyalospora. Based on the morphologic and genotypic
      characteristics, we propose a new species, Lichtheimia hongkongensis sp. nov., to
      describe this fungus, which caused rhinocerebral, gastrointestinal, and cutaneous
      mucormycosis, respectively, in 3 patients. A significant proportion of L.
      corymbifera associated with mucormycosis reported may be L. hongkongensis.

PMID- 20159376
TI  - Spectrum of activity, mutation rates, synergistic interactions, and the effects
      of pH and serum proteins for fusidic acid (CEM-102).
AB  - Fusidic acid (CEM-102) is a steroidal antimicrobial agent with focused Gram
      positive activity that acts by preventing bacterial protein synthesis via
      interacting with elongation factor G. A collection of 114 wild-type isolates (>
      80 species) was used to define the contemporary limits of fusidic acid spectrum
      against Gram-positive and Gram-negative species. Reference broth microdilution
      and anaerobic agar dilution methods were performed. Modifications of standardized
      test methods included adding 10% human serum and adjusting the medium pH to 5, 6,
      and 8. Synergy was assessed by the checkerboard method and time-kill studies.
      Mutational rates to resistance were determined at 4 x, 8 x, and 16 x MIC. Against
      Gram-positive pathogens, fusidic acid MIC values ranged from 0.06 to 32 microg/mL
      with the greatest potency against Staphylococcus aureus, Corynebacterium spp.,
      and Micrococcus luteus (MIC results, 0.25, < or = 0.12, and < or = 0.5 microg/mL,
      respectively). Enterococci and streptococci were less susceptible (MIC ranges, 2
      8 and 16-32 microg/mL, respectively). Fusidic acid activity against Gram-negative
      species was more limited (all MIC values, > or = 2 microg/mL) except for
      Empedobacter brevis, Moraxella catarrhalis and Neisseria meningitidis. A 4-fold
      increase in fusidic acid MIC results was observed when 10% serum was added to the
      broth. Decreasing medium pH to 5.0 to 6.0 negated the protein binding effects.
      Among the 8 antimicrobial combinations tested, gentamicin and rifampin enhanced
      the activity when combined with fusidic acid (no antagonism). Fusidic acid in
      vitro activity was most improved when combined with rifampin. Single-step
      mutational rates ranged from 1.2 x 10(-6) for 4x MIC to 9.8 x 10(-8) for 16 x
      MIC. In conclusion, these in vitro results for fusidic acid tested against
      contemporary strains confirm a persisting antimicrobial spectrum, especially
      against staphylococci and some other Gram-positive species.

PMID- 20159377
TI  - Antimicrobial activity of daptomycin tested against Staphylococcus aureus with
      vancomycin MIC of 2 microg/mL isolated in the United States and European
      hospitals (2006-2008).
AB  - We evaluated the activity of daptomycin (minimum inhibitory [MIC] and
      bactericidal [MBC] concentration) against Staphylococcus aureus strains with
      elevated (2 microg/mL) vancomycin MIC values. A total of 410 contemporary
      clinical S. aureus isolates (282 from the United States and 128 from Europe) with
      vancomycin MIC values of 2 microg/mL were tested by reference broth microdilution
      method. Vancomycin MBC and the presence of vancomycin-heteroresistant population
      (heterogeneous vancomycin-intermediate S. aureus [hVISA]) were evaluated in 31
      randomly selected strains. Overall, 97.3% of isolates were susceptible to
      daptomycin (MIC(90), 0.5 microg/mL). Daptomycin exhibited potent bactericidal
      activity with MBC values at the MIC concentration (74.2%) or 1 log(2) dilution
      above the MIC (25.8%). In contrast, vancomycin MBC was > or = 32 microg/mL in
      12.9% of strains tolerance, and 25.8% of strains tested positive for hVISA (AB
      BIODISK GRD Etest, Solna, Sweden). In conclusion, S. aureus strains with
      vancomycin MIC of 2 microg/mL showed high rates of hVISA and vancomycin
      tolerance. Daptomycin retained potent bactericidal activity against S. aureus
      with decreased susceptibility to vancomycin.

PMID- 20159378
TI  - Epidemiology of pediatric community-acquired bloodstream infections in a children
      hospital in Paris, France, 2001 to 2008.
AB  - In 2001 to 2008, we documented 483 cases of pediatric community-acquired
      bacteremia mostly because of Streptococcus agalactiae (< 4 days), Escherichia
      coli (4 days to 3 months), pneumococci (3 months to 5 years), and Staphylococcus
      aureus (> 5 years). Pneumococcal conjugate vaccination affected the serotype
      distribution of pneumococcal bacteremia but not its frequency. Serotype 19A
      represented 12% and 22% of pneumococci in the prevaccine and vaccine periods,
      respectively.

PMID- 20159379
TI  - Comparison of ultrarapid and rapid intravenous hydration in pediatric patients
      with dehydration.
AB  - OBJECTIVE: The purpose of this study is to test the efficacy of ultrarapidly
      infused vs rapidly infused intravenous (IV) hydration in pediatric patients with
      acute gastroenteritis and moderate dehydration. METHODS: Patients 3 to 36 months,
      with vomiting and/or diarrhea and moderate dehydration, were eligible. Subjects
      were randomly assigned "ultra" (50 mL/kg normal saline for 1 hour) vs "standard"
      (50 mL/kg normal saline for 3 hours) after failing an oral fluid challenge.
      Subjects were weighed and had serum electrolyte testing, and urine was obtained
      before/after IV hydration. Input/output and vital signs were tabulated hourly
      during the study. Subjects were discharged after fulfilling specified criteria. A
      follow-up questionnaire was completed 24 hours after discharge. Comparison data
      included success and timing of rehydration, number of patients who returned
      and/or were admitted, output during the rehydration period, laboratory
      differences, and serious complications. RESULTS: Eighty-eight of 92 subjects
      completed the study: 45 ultra and 43 standard. Four patients failed treatment (1
      ultra and 3 standard), were hospitalized, and excluded from the study. Groups
      were similar regarding sex, days of symptoms, episodes of vomiting/diarrhea
      before treatment, capillary refill time, tears, and vital signs and laboratory
      results. No subject had evidence of serious complications. Ninety-one percent of
      subjects completed the follow-up questionnaire. Seven ultra and 6 standard
      subjects returned. Six ultra subjects received oral fluid, one received IV fluid,
      and all were discharged. Five standard subjects received oral fluid, one received
      IV fluid, and all were discharged. CONCLUSION: Based on this pilot study,
      ultrarapid hydration for 1 hour preliminarily appears to be an efficacious
      alternative to standard rapid hydration for 3 hours and improves emergency
      department throughput time.

PMID- 20159380
TI  - Microneedle pretreatment improves efficacy of cutaneous topical anesthesia.
AB  - Methods to facilitate topical anesthesia for venipuncture are characterized by
      substantial limitations. This randomized double-blind study was undertaken to
      assess whether use of a quickly and painlessly applied microneedle system
      (functional microarray, FMA) to create punctures in the stratum corneum
      facilitates topical anesthesia in healthy adults. In 25 volunteers receiving
      topical dyclonine, FMA was applied to one forearm and a sham device in the other,
      followed by assessment of pain levels associated with application of a
      standardized stimulus at 5-minute intervals over an hour. Analysis of the primary
      end point, time required to achieve a significant degree of pain reduction (13 mm
      on a 100-mm scale), revealed that FMA significantly sped time to pain reduction
      (log-rank P = .007). Functional microarray also resulted in a greater degree of
      pain reduction (Kruskal-Wallis P < .0001). Functional microarray application had
      no adverse effects, and the device shows promise for facilitation of topical
      anesthesia.

PMID- 20159381
TI  - A new simple risk score in patients with acute chest pain without existing known
      coronary disease.
AB  - OBJECTIVE: To derive and validate a prediction rule in patients with acute chest
      pain (CP) without existing known coronary disease. METHODS: Cohort study
      including 2233 patients with CP. Based on clinical judgment, 1435 were discharged
      as very low risk and the remaining 798 underwent exercise tolerance test (ETT).
      END POINT: 6-month composite of cardiovascular death, nonfatal myocardial
      infarction, and revascularization. The prediction rule was derived from a
      randomly selected test cohort (n = 1106) summing factors of variables selected by
      multivariate regression analysis: CP score higher than 6 (factor of 3), male
      gender, age older than 50 years, metabolic syndrome, and diabetes mellitus
      (factor of 1, for each). The prediction rule was validated in the remaining
      cohort (n = 1127). All patients with CP were categorized into 3 groups: group A
      (prediction rule 0-1), B (2-4), or C (5-6). Outcomes and prognostic yield of ETT
      were compared among each group. RESULTS: In the test cohort, 55 patients (5%)
      reached the composite end point. Event rate increased as the prediction rule
      increased: 1% for group A, 6% for B, and 25% for C (P < .001). This pattern was
      confirmed in the validation cohort (P < .001). A normal ETT did not significantly
      improve the high (99%) negative predictive value in group A and did not succeed
      in excluding the composite end point (17%) in group C. CONCLUSIONS: In patients
      with acute CP without existing coronary disease, a prediction rule based on
      clinical characteristics provided a useful method for prognostication with
      possible implication in decision making.

PMID- 20159382
TI  - Clinical and bioavailability studies of sublingually administered atropine
      sulfate.
AB  - INTRODUCTION: The increased use of organophosphorus (OP) pesticides and the ever
      increasing possibility of terror groups using nerve agents underscore a need to
      develop effective and safe antidotes against OP poisoning. The objectives of the
      present study were to develop a novel atropine sulfate (AS) sublingual injection
      formulation, to create its bioavailability data in humans and to evaluate its
      suitability for field use with a view to obtain early therapeutic drug
      concentration in comparison to the conventional intramuscular route that provides
      a therapeutic peak of 6 to 8 ng/mL in blood at 30 minutes. METHODS: Two
      milligrams per 0.1 mL of AS was sublingually injected in 6 volunteers, and
      bioavailability and atropinization signs (blood pressure, pupil diameter, and
      heart rate) were noted. RESULTS: Human bioavailability curve was created, which
      was equivalent to 2 mg IM injection in amplitude within 10 minutes and describing
      a better curve thereafter. Peak plasma concentration of AS occurred at 15 minutes
      and was 21 ng/mL. Increase in heart rate became extremely significant at 5
      minutes (P < .0001) with maximum increase of 62% + or - 6% at 10 minutes after
      administration. Pupil diameter showed maximal increase of 58% + or - 21% at 15
      minutes (P < .01). CONCLUSIONS: Sublingual AS appears to have several advantages
      over conventional IM route including better bioavailability, rapid onset of
      action, and early atropinization. It is a safe and efficacious procedure with the
      potential to become an alternative to conventional IM injection, particularly in
      case of chemical terrorism scenario where hundreds of victims may require
      immediate atropinization simultaneously.

PMID- 20159383
TI  - Identification of an age cutoff for increased mortality in patients with elderly
      trauma.
AB  - OBJECTIVES: The chosen age cutoff for considering patients with trauma to be
      "elderly" has ranged from 55 to 80 years in trauma guidelines and studies. The
      goal of this study was to identify at what age mortality truly increases for
      older victims of trauma. METHODS: We performed a cross-sectional study of the
      Ohio Trauma Registry, a statewide database of all injured patients who died or
      were admitted for more than 48 hours to both trauma and nontrauma centers.
      Patients 16 years or older entered into the registry between January 1, 2003, and
      December 31, 2006, were included. Inhospital mortality rates were obtained and
      stratified by 5-year age intervals and by injury severity score (ISS). Rates
      between age groups were compared using logistic regression to identify
      significant differences in mortality. RESULTS: Included were 75 658 patients. In
      logistic regression, patients 70 to 74 years of age had significantly greater
      mortality than all younger age groups when stratified by ISS (P < or = .001
      .004). When considering other 5-year age groups as referent (40-44, 45-49, 50-54,
      55-59, 60-64, 65-69 years old), no other group was associated with significantly
      increased mortality, as compared to younger groups (P > .05 for all). CONCLUSION:
      Patients 70 to 74 years of age have significantly greater mortality than all
      younger age groups when stratified by ISS. Age cutoffs based on younger ages are
      not associated with significant increases in mortality. An age of 70 years should
      be considered as an appropriate cutoff for considering a patient to be elderly in
      future studies of trauma and development of geriatric trauma triage criteria.

PMID- 20159384
TI  - Optimization of initial energy for cardioversion of atrial tachyarrhythmias with
      biphasic shocks.
AB  - OBJECTIVE: Recommendations for optimal first-shock energies with biphasic
      waveforms are conflicting. We evaluated prospectively the relation between type
      and duration of atrial tachyarrhythmias and the probability of successful
      cardioversion with a specific biphasic shock waveform to develop recommendations
      for the initial energy setting aiming at the lowest total cumulative energy with
      2 or less consecutive shocks. METHODS: We analyzed 453 consecutive patients
      undergoing their first transthoracic electrical cardioversion, including 358
      attempts for atrial fibrillation (AF) and 95 attempts for atrial flutter (AFL) or
      atrial tachycardia (AT). A step-up protocol with a truncated exponential biphasic
      waveform starting at 50 J was used. Total cumulative energies were estimated
      under the assumption of a 2-tiered escalating shock protocol with different
      initial energy settings and a "rescue shock" of 250 J for AFL/AT or 360 J for AF.
      The initial energy setting leading to the lowest total cumulative energy was
      regarded as the optimal first-shock level. RESULTS: Cardioversion was successful
      in 448 patients (cumulative efficacy, 99 %). In patients with AFL/AT, the lowest
      total cumulative energy was attained with an initial energy setting of 50 J. In
      patients with AF, lowest values were achieved with an initial energy of 100 J for
      arrhythmia durations of 2 days or less and an initial energy of 150 J for
      arrhythmia durations of more than 2 days. CONCLUSION: We recommend an initial
      energy setting of 50 J in patients with AFL/AT, of 100 J in patients with AF 2
      days or less, and of 150 J with AF more than 2 days.

PMID- 20159385
TI  - Circadian pattern of intubation rates in ED patients with congestive heart
      failure.
AB  - PURPOSE: A previous study showed that pulmonary edema patients presenting between
      noon and 4 pm have the highest rates of myocardial infarction and death. We
      hypothesized that the highest intubation rates would also occur at these times.
      BASIC PROCEDURES: We performed a retrospective cohort study of consecutive
      patients seen by emergency department physicians in 15 hospital emergency
      departments (1996-2003). MAIN FINDINGS: Of 3.6 million visits in the database,
      39,795 (1.1%) patients had congestive heart failure. We found statistically
      significant circadian variations in intubation rates. Patients arriving between
      midnight and 4 am had the highest intubation rates (4.1%), and those arriving
      between noon and 4 pm had the lowest (1.2%) (difference, 2.9%; 95% confidence
      interval, 2.4%-3.4%; P < .0001). CONCLUSION: We found significant circadian
      variation in intubation rates, with a marked increase around midnight.
      Pathological mechanisms causing patients with congestive heart failure to require
      intubation may differ from those resulting in myocardial infarction or death.

PMID- 20159386
TI  - Diagnostic value of ischemia-modified albumin in patients with suspected acute
      coronary syndrome.
AB  - INTRODUCTION: Ischemia-modified albumin (IMA) has been proposed as a useful rule
      out marker for the diagnosis of acute coronary syndrome (ACS) in the emergency
      department. This study evaluated the ability of IMA to predict the acute
      myocardial infarction (AMI) diagnosis in a population of chest pain patients.
      METHODS: The study population comprised 107 subjects (men, 62%; women, 38%)
      admitted with suspected ACS. None of the patients had ST-segment elevations that
      qualified for immediate revascularization. Ischemia-modified albumin was
      determined from serum with albumin cobalt binding test (Inverness Medical
      Innovations Inc, Stirling, UK). Furthermore, cardiac troponin T, creatinine
      kinase MB mass, myoglobin, and heart-type fatty acid binding protein (H-FABP)
      were determined on arrival, after 6 to 9 hours, and after 12 to 24 hours. All
      patients had at least 2 blood samples taken to exclude/verify the AMI. AMI was
      defined by a cardiac troponin T level greater than 0.03 microg/L. RESULTS: Thirty
      three percent of the patients (n = 35) had a final diagnosis of AMI. The
      sensitivity of admission IMA for a final diagnosis of ACS was 0.86 (95%
      confidence interval [95% CI], 0.69-0.95). Specificity was 0.49 (95% CI, 0.36
      0.60). Negative predictive value was 0.88 (95% CI, 0.72-0.95). The optimal cutoff
      threshold derived from the receiver operating characteristics (ROC) curve (ROC
      analysis) was determined as 91 U/mL. The area under the ROC curve was 0.73.
      Ischemia-modified albumin did not, at any time, provide superior sensitivity or
      specificity compared with other biomarkers. We do not find the data supportive of
      IMA as a standard marker in the emergency department.

PMID- 20159387
TI  - Management of motorcycle accident-related blunt hepatic injury-a different
      strategy.
AB  - BACKGROUND: In motorcycle accidents, especially in an urban area with lightweight
      motorcycles, the belly of the motorcyclist is not protected, and this makes this
      type of trauma a cause of blunt hepatic injuries. This study investigated the
      effect and safety of using nonoperative management and selective early
      angioembolization to treat patients with blunt liver injuries as a result of
      motorcycle accident. METHODS: This was a retrospective study of the hepatic
      injuries sustained by motorcyclists involved in traffic accidents. We collected
      patient demographic information, the severity of total injuries, grade of liver
      injury, associated concomitant injuries, management scheme, and outcome of
      patients from 2006 to 2007. These patients were treated nonoperatively with
      selective early angioembolization and close monitoring in our intensive care unit
      (ICU). RESULTS: We reviewed the cases of 266 patients sustaining blunt abdominal
      injuries. Thirty-four patients (12.78%) had hepatic injuries. All survived with
      no obvious morbidity, and no further invasive procedures were performed after
      admission to ICU. There was no significant association between grade of injury
      and ICU length of stay (P = .073), but there was a significant association
      between grade and in-patient length of stay on our regular ward (P = .001).
      CONCLUSION: Most patients with hepatic injury caused by motorcycle accidents can
      be treated safely by nonoperative management. Early selective angioembolization
      improved the success of nonoperative management of blunt liver injury without
      other surgical intervention. Routine follow-up with computed axial tomography
      scans and endoscopic retrograde cholangiopancreatography may not be necessary
      because complications associated with hepatic injuries were rare.

PMID- 20159388
TI  - Significance of left circumflex artery-related acute myocardial infarction
      without ST-T changes.
AB  - INTRODUCTION: Left circumflex (LC)-related acute myocardial infarction (AMI)
      presenting without ST-T changes has been underdiagnosed in the emergency
      department. There is little information on its clinical features and
      significance. AIMS: The aims of the study were to investigate the clinical
      characteristics and outcomes of LC-related AMI without ST-T changes. POPULATION
      AND METHODS: Ninety-six patients were admitted for LC-related AMI. Comparisons
      between those with and without ST-T changes were analyzed. RESULTS: Twenty-two
      patients (23%) did not have ST-T changes, whereas 74 patients (77%) had them.
      Patients without ST-T changes had younger age (55.6 + or - 16.8 vs 62.6 + or -
      12.0 years, P = .03), fewer presented as Killip III/IV (4.5% vs 27.4%, P = .02)
      and with lower creatine kinase (1647.3 + or - 1602.2 vs 2778.2 + or - 2343.3
      IU/L, P = .037) and creatine kinase-MB (136.8 + or - 130.3 vs 247.7 + or - 200.0
      IU/L, P = .017), and more were with concurrent culprit lesion in the middle or
      distal LC and right- or balanced-dominant coronary circulation (86.4% vs 44.6%, P
      < .001). During follow-up, the need for repeat percutaneous coronary intervention
      (48.6% vs 45.5%, P = .40) and recurrent infarction (13.5% vs 13.6%, P = .62) were
      similar between the 2 groups. The 30-day mortality (0% vs 5.4%, P = .35) and
      overall mortality rate (4.5% vs 12.2%, P = .28) between them were not different
      statistically. CONCLUSION: The relatively lower prevalence of LC-related AMI
      without ST-T changes in the study might be underestimated. These patients have
      smaller infarct size than patients with ST-T changes without differences in the
      short- and long-term outcomes between them.

PMID- 20159389
TI  - Incidence, clinical presentation, and management of constipation in a pediatric
      ED.
AB  - OBJECTIVES: The study aimed to assess, in pediatric patients presenting to the
      emergency department (ED), the incidence of visit to the ED for functional
      constipation (FC), symptoms, signs of presentation, and management from ED
      physicians. DESIGN: This is a retrospective study of hospital records for a
      period of 1 year at the ED of "Bambino Gesu" Children's Hospital, Rome, Italy.
      Children younger than 15 years discharged from ED with a diagnosis of FC in the 1
      year period were included. INTERVENTIONS: We analyzed medical records of 202
      patients (<15 years) with FC diagnosis at discharge. Main outcome measures
      included incidence, demographic characteristics, clinical presentations of FC
      patients, and ED physicians' interventions. RESULTS: Two hundred two FC cases
      were studied in a 12-month study period. Compared with the total number of ED
      consultations, the incidence of FC was 0.4%. The number of patients 4 years or
      younger was much higher than patients older than 4 years (P < .0001). Bowel
      frequency of 3 bowel movements or less per day, acute abdominal pain, and stool
      retention were found to be significantly more frequent than the other presenting
      symptoms (P < .0001). The number of patients beginning a therapy after ED
      discharge was significantly higher compared with that already treated before ED
      visit (P < .0001). Discharged patients were referred to community pediatricians
      significantly more frequently than to pediatric gastroenterologists (P = .003).
      CONCLUSIONS: Emergency department physicians have an important role in the
      diagnosis and management of FC despite its relatively low incidence. Indeed, ED
      intervention in many cases leads not only to recognition this disease but also to
      an approach for therapeutic strategy, avoiding complications of chronic
      constipation.

PMID- 20159390
TI  - Outcomes from low versus high-flow cardiopulmonary resuscitation in a swine model
      of cardiac arrest.
AB  - BACKGROUND: Return of spontaneous circulation (ROSC) is improved by greater vital
      organ blood flow during cardiopulmonary resuscitation (CPR). We tested the
      hypothesis that myocardial flow above the threshold needed for ROSC may be
      associated with greater vital organ injury and worse outcome. METHODS: Aortic and
      right atrial pressures were measured with micromanometers in 27 swine. After 10
      minutes of untreated ventricular fibrillation, chest compression was performed
      with an automatic, load-distributing band. Animals were randomly assigned to
      receive flows just sufficient for ROSC (low flow: target coronary perfusion
      pressure = 12 mm Hg) or well above the minimally effective level (high flow:
      coronary perfusion pressure = 30 mm Hg). Myocardial flow was measured with
      microspheres, defibrillation was performed after 3.5 minutes of CPR, and ejection
      fraction was measured with echocardiography. RESULTS: Return of spontaneous
      circulation was achieved by 9 of 9 animals in the high-flow group and 15 of 18 in
      the low-flow group. All animals in the high-flow group defibrillated initially
      into a perfusing rhythm, whereas 12 of 15 animals achieving ROSC in the low-flow
      group defibrillated initially into pulseless electrical activity (P < .05, Fisher
      exact test). Compared with animals in the low-flow group, animals in the high
      flow group had shorter resuscitation times, higher mean aortic pressures at ROSC,
      and higher ejection fractions at 2 hours post-ROSC (all P < .05). CONCLUSION:
      High-flow CPR significantly improved arrest hemodynamics, rates of ROSC, and post
      ROSC indicators of myocardial status, all indicating less injury with higher
      flows. No evidence of organ injury from vital organ blood flow substantially
      above the threshold for ROSC was found.

PMID- 20159391
TI  - A bedside ultrasound sign of cardiac disease: the left atrium-to-aorta diastolic
      diameter ratio.
AB  - PURPOSE: This study evaluated a simple ultrasound method to detect left atrial
      (LA) enlargement by comparing the diameters of the LA and aortic root.
      PROCEDURES: The LA and aortic diameters, the LA volume index (LAVI), and
      significant echo findings were analyzed in 101 consecutive echocardiograms. Mean
      LAVI and the prevalence of an abnormal echo were compared between groups in which
      the ratio of the LA diameter to aortic diameter in diastole was >1 vs < or = 1.
      FINDINGS: Left atrial-to-aortic diameter ratio increased with LAVI (r = 0.64, P <
      .001). Left atrial-to-aortic diameter ratio >1 vs < or = 1 was noted in 45% vs
      55% of patients and had a mean (+ or - SD) LAVI = 39 + or - 12 vs 27 + or - 7
      mL/m(2) (P < .001) and a 78% vs 43% prevalence of an abnormal echo (P < .001).
      CONCLUSION: The left atrium-to-aorta diastolic diameter ratio can detect LA
      enlargement and may be useful as a quick bedside technique to screen for cardiac
      disease.

PMID- 20159392
TI  - Increased rate of central venous catheterization procedures in community EDs.
AB  - OBJECTIVE: Central venous catheterization (CVC) is integral to the emergency
      department (ED) treatment of critically ill patients, such as those receiving
      early goal-directed therapy for severe sepsis. No previous studies have described
      the overall use of CVC in community EDs. The objective of this study was to
      estimate the overall frequency and temporal trends in CVC use in a sample of
      patients visiting community EDs. METHODS: This was a retrospective observational
      study of 2.97 million patient visits at 28 community EDs (range of annual visits,
      10 837-110 136) from January 2004 to February 2008. Data were obtained from a
      community-based research consortium. Central venous catheterization procedures
      were aggregated at the hospital level for each study year. Trends in CVC use were
      evaluated using linear regression. RESULTS: Three thousand four hundred eighty
      nine patient visits (0.12% of all ED patient visits) had a CVC procedure
      performed in the ED. The overall rate of CVC procedures per 1000 ED patient
      visits increased from 0.87 (95% confidence interval [CI(95%)], 0.80-0.95) in 2004
      to 1.62 (CI(95%), 1.38-1.91) procedures in 2008 (P value for trend = .003). There
      was wide variability in the frequency of CVC procedures performed among EDs,
      ranging from a low of 0.27 (CI(95%), 0.18-0.42) to a high of 7.58 (CI(95%), 6.27
      9.17) procedures per 1000 ED visits. The CVC procedure rates were lower in the 8
      rural EDs (0.99 CVCs per 1000 ED patient visits [CI(95%), 0.91-1.07] compared
      with the 20 urban EDs (1.22 CVCs [CI(95%), 1.18-1.27]; P < .001). An increasing
      rate of CVC procedures during the study period was observed in urban EDs (0.84
      1.94 CVCs per 1000 ED patient visits; P value for trend = .005) but not in rural
      EDs (1.1-0.93; P value for trend = .41) during the study period. CONCLUSION: The
      overall rate of CVC increased from 2004 to 2008. However, there was a wide
      variation among Eds, and the CVC rate was lower in rural compared with urban EDs.
      The increase in CVC use in urban EDs may reflect more intensive therapy in the
      management of ED patients with acute illness or injury. Future efforts are needed
      to optimize best practices for the use of CVC in community ED practices and to
      characterize factors responsible for urban rural differences in the rate of CVC
      procedures.

PMID- 20159393
TI  - Pelvic examination is unnecessary in pregnant patients with a normal bedside
      ultrasound.
AB  - OBJECTIVE: This study examines the necessity of a formal pelvic examination in
      patients with early pregnancy-related complaints and an intrauterine pregnancy on
      bedside ultrasound (US). METHODS: Data were prospectively collected on emergency
      department (ED) patients presenting with early pregnancy complaints and bedside
      US evidence of intrauterine pregnancy. All patients received a formal pelvic
      examination with cervical testing for sexually transmitted pathogens. Disposition
      decisions based on pelvic examination findings were compared with disposition
      decisions based on ultrasound findings alone. RESULTS: Over a 13-month period, 50
      patients entered the study. Mean estimated gestational age was 8.6 (+ or - 0.4)
      weeks. Abnormal speculum examination findings included vaginal blood (19 [38%])
      and cervical discharge (3 [6%]). Abnormal bimanual findings included adnexal
      tenderness (6 [12%]) and uterine tenderness (4 [8%]). One patient (2.5%) had a
      positive antigen test for Chlamydia trachomatis. Emergency department diagnoses
      were threatened abortion (30 [60%]), intrauterine pregnancy (11 [22]), abdominal
      pain (8 [16%]), and ovarian cyst (1 [2%]). Three patients (6%) had incidental
      urinary tract infections. All patients were discharged from the ED. No management
      changes were made based on the pelvic examination. CONCLUSION: In patients with a
      US-documented viable pregnancy, the pelvic examination did not contribute to the
      patient's immediate obstetric treatment. Occult cervical pathogens may be present
      in these patients.

PMID- 20159394
TI  - The effect of ED crowding on education.
AB  - OBJECTIVE: We studied if emergency department (ED) crowding affects the quality
      of resident and medical student education on individual patient encounters.
      METHODS: We performed a cross-sectional study of a ED faculty-learner
      interactions over a 5-week period in an academic ED. Research assistants
      administered surveys to residents and senior medical students assessing attending
      physicians on 4 domains (teaching, clinical care, approachability, and
      helpfulness) using a scale (ER score for teaching on individual patients)
      validated for use during ED rotations. Each domain was assessed on a 5-point
      scale with a highest score of 20 representing superb/outstanding. We tested the
      association between measures of ED crowding (waiting room number, occupancy,
      number of admitted patients, and patient-hours) at the time of assessment with
      the ER score and individual domain scores using correlation coefficients and
      regression analysis with clustering on the attending physician. RESULTS: Forty
      three residents (22 ED, 21 non-ED) and 3 medical students assessed 34 attending
      physicians in 352 separate encounters. Median ER score was 16/20 (interquartile
      range, 12-16). Emergency department crowding levels and ER scores on individual
      patients were not significantly correlated, nor were ED crowding and individual
      domains. In the adjusted analysis, ED crowding was not associated with an ER
      score of 16 or higher, nor was any ED crowding measure associated individual
      assessments of teaching, clinical care, approachability, or helpfulness.
      CONCLUSION: Emergency department crowding is not associated with the quality of
      education on individual patients.

PMID- 20159395
TI  - The utility of serial peak flow measurements in the acute asthmatic being treated
      in the ED.
AB  - BACKGROUND: Peak flow is used extensively in emergency departments (EDs) to both
      assess asthma patient's status on arrival as well as to document clinical
      improvement during treatment. Many algorithms suggest serial peak expiratory flow
      (PEF) measurements during an ED stay. OBJECTIVE: The aim of the study was to
      assess the contribution of serial PEF in describing the overall improvement of
      asthmatics over the course of an ED visit for acute exacerbation of their asthma.
      METHODS: This was a prospective institutional review board-approved study of
      mild/moderate asthmatics presenting to an inner-city ED serving a large Latino
      population. Peak expiratory flow was measured before treatment (baseline PEF) and
      after each inhaled treatment (PEF post RX#1, PEF post RX#2, PEF post RX#3) while
      in the ED. RESULTS: One hundred consecutive patients made up this study cohort.
      The change from baseline PEF to PEF #1 represented 86% (95% confidence interval
      [CI], 76%-96%) of the total improvement experienced by these patients with
      asthma. The change from PEF post RX#1 to PEF post RX#2 represented 7.5% (95% CI, 
      4.2% to 26%) of the total improvement and PEF post RX#2 to PEF post RX#3
      represented 8.6% (95% CI, -1% to 34%) of the total PEF improvement seen.
      LIMITATION: No correlation between outcome and PEF% of predicted was made or
      implied. CONCLUSION: The improvement in PEF seen after the first ED inhaled
      therapy appears to describe most of the total improvement seen in asthmatic
      patients. Subsequent PEFs provided little additional information.

PMID- 20159396
TI  - The impact of warm weather on mass event medical need: a review of the
      literature.
AB  - Over the last 20 years, interest in medical need at mass events has increased.
      Many studies have been published identifying the characteristics of such events
      that significantly impact the number of patients who seek care. Investigators
      agree that weather is one of the most important variables. We performed a
      literature search using several biomedical databases (MEDLINE via PubMed, the
      Cochrane database, BMJ's Clinical Evidence compendium, and Google Scholar) for
      articles addressing the effect of weather on medical need at mass events. This
      search resulted in 8 focused articles and several other resources from the
      reference sections of these publications. We found that the early literature is
      composed of case reports and predominantly subjective observations concerning the
      impact of weather on medical need. Most investigators agree upon a positive
      relationship between heat/humidity and the frequency of patient presentation.
      More recent authors make attempts at quantifying the relationship and propose
      prediction models for patient volume and medical personnel requirements. We
      present an ancestral review of these studies, discuss their results collectively,
      and propose a simplified algorithm for predicting patient volume at mass events.
      This review is intended for event planners and mass event emergency medical
      personnel for planning future events. We also hope to stimulate further study to
      develop and verify prediction models.

PMID- 20159397
TI  - The effects of continuous positive airway pressure on plasma brain natriuretic
      peptide concentrations in patients presenting with acute cardiogenic pulmonary
      edema with preserved left ventricular systolic function.
AB  - BACKGROUND: It has been established that plasma brain natriuretic peptide (BNP)
      concentrations in patients with acute cardiogenic pulmonary edema (ACPE) increase
      in proportion to heart failure. OBJECTIVES: The aim of this study is to assess
      the effects of continuous positive airway pressure (CPAP) treatment on plasma BNP
      concentrations in patients presenting with ACPE with preserved left ventricular
      (LV) systolic function. METHODS: This was a prospective, observational single
      center study in the emergency unit of Valduce Hospital. Twelve patients (group A)
      presenting with ACPE and preserved LV ejection fraction and 14 patients (group B)
      with systolic heart dysfunction (LV ejection fraction <45%) underwent CPAP (10 cm
      H(2)O) through a face mask and standard medical therapy. Plasma BNP
      concentrations were collected immediately before CPAP and 3, 6, and 24 hours
      after treatment. All patients underwent a morphological echocardiographic
      investigation shortly before CPAP. RESULTS: Three hours after admission, BNP
      significantly decreased in patients with ACPE and preserved LVEF (from 998 + or -
      467 pg/mL to 858 + or - 420 pg/mL; P < .05), whereas in those with systolic
      dysfunction, BNP was higher than during baseline (from 1352 + or - 473 pg/mL to
      1570 + or - 595 pg/mL; P < .05). CONCLUSIONS: The preliminary results of the
      present study show that CPAP, after 3 hours, lowers BNP levels in patients with
      ACPE and preserved LV systolic function compared with patients affected by
      systolic ACPE dysfunction where BNP levels do not change significantly.

PMID- 20159398
TI  - Routine testing in patients with asymptomatic elevated blood pressure in the ED.
AB  - STUDY OBJECTIVE: There are no clear recommendations for the diagnostic evaluation
      of patients who present to the emergency department (ED) with asymptomatic
      elevated blood pressure. In patients presenting with asymptomatic elevated blood
      pressure in the ED, we measured the prevalence of abnormalities on a basic
      metabolic profile (BMP) that led to hospital admission as well as the prevalence
      of diminished renal function. METHODS: This is a cross-sectional study at 2 urban
      teaching EDs with a largely African American population. Adult patients (> or =
      18 years) with a triage diastolic blood pressure (BP) 100 mm Hg or higher and
      without symptoms suggestive of acute end-organ damage were enrolled. All patients
      had a BMP sent. The primary outcome measured was abnormalities on the BMP that
      led to hospital admission. The secondary outcome measured was the prevalence of
      diminished renal function (glomerular filtration rate <60 mL min(-1) 1.73 m(-2)).
      RESULTS: One hundred sixty-seven patients with asymptomatic elevated BP were
      studied. Twelve (7.2%; 95% confidence interval, 3%-11%) patients were admitted
      due to abnormal results on the BMP. Twenty-seven (16.2%; 95% confidence interval,
      11%-21%) patients met the secondary outcome measure of diminished renal function
      (glomerular filtration rate <60 mL min(-1) 1.73 m(-2)). CONCLUSION: In a
      homogenous African American population presenting to the ED with asymptomatic
      elevated BP, there is a relatively high prevalence of abnormalities on the BMP
      that led to hospital admission. We suggest routine testing of a serum creatinine
      should be strongly considered in a largely African American patient population
      with asymptomatic elevated BP in the ED.

PMID- 20159399
TI  - Early goal-directed therapy: on terminal life support?
AB  - Early goal-directed therapy (EGDT) has become regarded as the standard of care
      for the management of patients with severe sepsis and septic shock. The elements
      of EGDT have been bundled together as the "Sepsis Bundle," and compliance with
      the elements of the bundle is frequently used as an indicator of the quality of
      care delivered. The major elements of EGDT include fluid resuscitation to achieve
      a central venous pressure of 8 to 12 cm of water, followed by the transfusion of
      packed red cells or an inotropic agent to maintain the central venous oxygen
      saturation higher than 70%. Although the concept of early resuscitation is a
      scientifically sound concept, we believe that the major elements of the sepsis
      bundle are fatally flawed.

PMID- 20159400
TI  - Treatment of exertional heat injuries with portable body cooling unit in a mass
      endurance event.

PMID- 20159401
TI  - The impact of H1N1 influenza A virus pandemic on the emergency medical service in
      Kobe.

PMID- 20159402
TI  - In response to .... Pre-excitation syndromes: diagnostic considerations.

PMID- 20159403
TI  - Caveats in preexcitation-related atrial fibrillation.

PMID- 20159404
TI  - Special considerations apply when Streptococcus bovis is the culprit pathogen.

PMID- 20159405
TI  - Penetrating neck trauma causing tracheal rupture, spinal cord injury, and massive
      pneumocephalus.
AB  - We describe a case in which tracheal, esophageal, and spinal cord injuries
      associated with massive pneumocephalus were caused by a flying chainsaw segment.
      To our knowledge, this is the first such case reported in the medical literature.
      The management challenges inherent in this exceedingly rare combination of
      injuries are discussed, and a novel theory explaining the possible
      pathophysiological mechanism that led to pneumocephalus in our patient is put
      forth.

PMID- 20159406
TI  - Acute deep vein thrombus due to May-Thurner syndrome.
AB  - A 63-year-old white woman with a history of hypertension, hyperlipidemia,
      hypothyroidism, and transient ischemic attack, on Premarin, presented with a 2
      week history of worsening edema and pain on the left side of the lower extremity
      associated with purplish discoloration and decreased temperature after a
      prolonged car travel. Physical examination revealed 2+ edema from the midthigh to
      the toes associated with purpuric discoloration. All arterial pulses were 4+.
      Ultrasound examination demonstrated an acute deep vein thrombus extending from
      the external iliac veins down throughout the visualized veins of the left calf.
      The patient was started on intravenous heparin and underwent venogram with
      subsequent thrombolysis. After 48 hours of alteplase infusion, balloon
      angioplasty was performed and 2 stents were placed in the left common and
      external iliac veins. Premarin was discontinued and she remains on oral
      anticoagulation with Coumadin. The patient did well clinically and a second
      ultrasound showed interval improvement. There is significant family history but
      no personal history of thrombotic events; however, thrombophilia evaluation is
      unremarkable.

PMID- 20159407
TI  - Acute multiple organ failure with imidacloprid and alcohol ingestion.
AB  - Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine]
      belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl
      neonicotinoid compounds. Animal studies indicate relatively low toxicity to
      mammals due to nicotinic receptor resistance. Human poisoning is usually mild,
      and reports are quite limited. Here, we report a case of ingestion of alcohol
      with an insecticide containing imidacloprid. Clinical manifestation included mild
      disorientation, followed by bradycardia, ventricular arrhythmia, and
      cardiopulmonary arrest. Acute multiple organ failure, including oliguric kidney
      injury, acute lung injury, hypotension, and metabolic acidosis developed within
      hours of ingestion. Renal replacement therapy, including intermittent
      hemodialysis and continuous venovenous hemodialysis, quickly corrected the
      metabolic acidosis with better blood pressure. Despite original belief that
      imidacloprid has low mammalian toxicity, there is increasing evidence that
      imidacloprid may cause heart, kidney, and other organ damages and even death
      besides gastrointestinal irritation and neurological symptoms. The role of
      aldehyde oxidase, imidacloprid metabolites, and ethanol alcohol consumption in
      the pathogenesis of imidacloprid toxicity needs further study.

PMID- 20159408
TI  - Ultrasound identification of traumatic pneumobilia.
AB  - A 65-year-old woman presented to the emergency department with low back pain
      after being hit by a truck at low speed. Although her abdominal examination
      showed benign results, an extended Focused Assessment With Sonography in Trauma
      ultrasound examination was performed and incidentally demonstrated evidence of
      pneumobilia. There were no additional intra-abdominal injuries noted. Subsequent
      computed tomography and magnetic resonance cholangiopancreatography confirmed
      these findings. The etiology of traumatic pneumobilia is discussed with a brief
      review of the literature on the subject.

PMID- 20159409
TI  - Cardiogenic shock associated with reversible dilated cardiomyopathy during
      therapy with regular doses of venlafaxine.
AB  - We report a cardiac complication in a patient treated with regular doses of
      venlafaxine. A 49-year-old man with prior normal cardiac function and stable
      chronic hepatitis C was treated for a major depressive disorder with usual doses
      of venlafaxine during an 8-month period until the occurrence of a cardiogenic
      shock in a context of dilated cardiomyopathy. Three months after withdrawal of
      the drug, the left ventricular ejection fraction returned to normal values.
      Cardiomyopathy is a rare complication with high doses of venlafaxine that was not
      previously reported in patients free of prior cardiac disease and cardiomyopathy
      and treated with usual doses (initially 150 mg daily; after 3 months, 75 mg
      daily). An objective assessment revealed that venlafaxine was probably implied in
      the subsequent development of cardiomyopathy when considering the Naranjo
      Probability Scale. Physicians who usually prescribe venlafaxine have to be
      briefed on such potential cardiac adverse effects even with usual doses.

PMID- 20159410
TI  - Brugada-pattern electrocardiogram in propranolol intoxication.
AB  - Brugada syndrome is characterized by the electrocardiographic (ECG) pattern of
      right bundle-branch block (RBBB) with a high take-off, coved ST-segment elevation
      in the precordial leads V1 to V3, and the risk of sudden cardiac death.
      Typically, there is no evidence of structural heart disease. In many cases,
      Brugada syndrome has been linked to a mutation of the gene SCN5A, which encodes
      for the fast cardiac sodium channel. In patients with the Brugada syndrome,
      pharmacologic sodium channel blockade can increase the degree of ST-segment
      elevation. Interestingly, even in patients with a normal baseline ECG and no
      clinical suggestion of the Brugada syndrome, toxic doses of class I
      antiarrhythmic agents as well as toxicities with several nonantiarrhythmic drugs
      that possess sodium channel blocking properties can induce the Brugada ECG
      abnormality. Specifically, the beta-receptor blocker propranolol, at high doses,
      binds to the cardiac sodium channels and inhibits sodium uptake. In this report,
      we describe a case of severe propranolol toxicity, which resulted in the Brugada
      ECG pattern in an otherwise healthy individual who had no clinical or ECG
      suggestion of the genetically determined Brugada syndrome.

PMID- 20159411
TI  - Hyaluronidase for the management of dextrose extravasation.
AB  - Intravenous catheter malfunction causing extravasation is a common occurrence in
      the emergency department (ED). A 17-year-old girl who had a syncopal episode was
      given an ampule of dextrose 50% water into her antecubital region by emergency
      medical services. During her evaluation at the ED, she developed erythema and
      swelling in the antecubital region where the dextrose was given and extravasation
      was suspected. Most extravasations have relatively minor sequelae, but once an
      extravasation has occurred, damage can continue for months and involve nerves,
      tendons, and joints. If treatment is delayed, surgical debridement, skin
      grafting, and even amputation have been reported in literature. Hyaluronidase is
      a parenteral protein enzyme traditionally derived from bovine testicular tissue.
      Hyaluronidase is used as adjunct therapy to increase the absorption and
      dispersion of other injected drugs. The drug has also been used as an adjunct to
      nonpharmacologic management of extravasation of selected antineoplastic agents
      and other irritants. Although hyaluronidase does not have a Food and Drug
      Administration indication for dextrose extravasation, literature has shown
      improved outcomes for other hyperosmolar substances. Hyaluronidase was used by
      injecting 0.2 mL (150 U/1 mL) with a 25-gauge needle at 5 different sites along
      the leading edge of erythema. The patient's symptoms improved, and there were no
      complications noted at follow-up at 48 hours and at 6 months. The use of
      hyaluronidase should be considered for the management of dextrose extravasations
      and other extravasations.

PMID- 20159412
TI  - Prinzmetal-variant angina in a patient using zolmitriptan and citalopram.
AB  - Prinzmetal-variant angina is a syndrome of chest pain caused by myocardial
      ischemia secondary to reversible coronary artery vasospasm, which may occur in
      angiographically normal and diseased coronary arteries. It typically occurs at
      rest and is accompanied by transient ST-segment elevation. Although the
      underlying pathophysiology is not well established, coronary spasm secondary to
      increased serotonergic activity as well as increased sympathetic activity may
      prevail. Coronary artery spasm can be invoked by antimigraine therapy and also by
      drugs having serotonergic activity such as ergonovine and ergotamine. Prinzmetal
      variant angina may be complicated with acute myocardial infarction, ventricular
      arrhythmias as well as sudden cardiac death. We report a case of 48-year old
      woman presenting with chest pain and diffuse ST-segment elevation on
      electrocardiography during an episode of angina, while she was taking
      zolmitriptan 5 mg/d and citalopram 20 mg/d for migraine and depression,
      respectively. Coronary angiography (performed because of prolonged angina and
      presence of diffuse ST-segment elevation on electrocardiography) revealed that
      diffuse narrowing of left anterior descending coronary artery alleviated after
      intracoronary nitrate therapy. The most likely cause of myocardial infarction was
      coronary artery spasm because of the possible increased serotonergic activity
      secondary to concomitant use of zolmitriptan and citalopram.

PMID- 20159413
TI  - Prolonged and profound therapeutic hypothermia for the treatment of "brain death"
      after a suicidal intoxication. Challenging conventional wisdoms.
AB  - Therapeutic hypothermia has been reported to improve the neurologic outcome of
      comatose survivors of out-of-hospital cardiac arrest. The use of therapeutic
      hypothermia in patients who have had an acute ischemic-hypoxic brain injury after
      a suicidal intoxication has not been previously reported. We present the case of
      a young woman who presented comatose to our emergency department after attempting
      suicide by ingesting diazepam and a bottle of antifreeze (ethylene-glycol).
      Despite aggressive supportive care, the patient progressed to what appeared to be
      clinical brain death. At this point, the patient was managed with therapeutic
      hypothermia for 36 hours. The patient awoke within 48 hours of rewarming and made
      a complete and full neurologic recovery. In conclusion, this case has important
      implications in the management of patients who have had an acute ischemichypoxic
      brain injury. Inappropriately labeling such patients as "brain dead" will result
      in the failure to institute therapeutic hypothermia and other advanced
      neuroprotective interventions in patients who could be salvaged with a good
      neurologic outcome.

PMID- 20159414
TI  - Atropine aggravates signs and symptoms of Takotsubo cardiomyopathy.
AB  - We present a novel case of Takotsubo cardiomyopathy, associated with worsening
      chest pain and T-wave inversions on electrocardiogram after atropine use. Our
      patient was an 82-year-old woman who complained of substernal chest discomfort of
      5 hours duration. Atropine 0.5 mg was administered intravenously by the emergency
      medical service for symptomatic bradycardia. The patient subsequently complained
      of worsening chest pain and developed new T-wave inversions on the
      electrocardiogram. Cardiac catheterization was diagnostic and revealed normal
      coronary arteries but akinesis of the apical segment. Although the pathogenesis
      of Takotsubo cardiomyopathy is not completely understood, catecholamine-mediated
      myocardial stunning due to enhanced sympathetic activity is the most widely
      accepted underlying mechanism. The withdrawal of parasympathetic drive in such
      cases should exacerbate sympathetic activity, leading to the genesis or worsening
      of disease activity. The role of atropine in relation to Takotsubo cardiomyopathy
      has been questioned before. However, it was always in the setting of general
      anesthesia induction, at which time atropine had been used for reversal of
      symptomatic bradycardia; consequently, determining the exact role of atropine in
      the disease process was difficult. Our patient received only atropine and
      therefore illustrated its capacity to worsen signs and symptoms of Takotsubo
      Cardiomyopathy. Because patients with Takotsubo cardiomyopathy may present with
      recurrent chest pain, we would recommend caution against the use of atropine for
      symptomatic bradycardia in such patients in the emergency department.
      Transcutaneous pacemaker should be preferred.

PMID- 20159415
TI  - Spontaneous diaphragmatic rupture complicated with perforation of the stomach
      during Pilates.
AB  - Diaphragmatic rupture (DR) is most commonly seen after a blunt trauma. It rarely
      occurs spontaneously. Many cases of spontaneous DR followed by strenuous sports
      activity have been reported in the medical literature. However, there has been no
      previous report on a case of spontaneous DR after a static sport activity. We
      report the case of a 29-year old woman who presented to the emergency department
      (ED) with pain in the epigastric area that started 1 day before visiting the ED
      during deep breathing in Pilates. The radiography and computed tomography of her
      chest demonstrated a left diaphragmatic rupture complicated with the perforation
      of viscera. She immediately underwent left thoracotomy. In addition, primary
      repair of the diaphragm and stomach was performed. On the basis of our findings,
      we conclude that spontaneous DR may be caused by a static sport activity, such as
      Pilates, causing a serious life threatening condition.

PMID- 20159416
TI  - Aberrant internal carotid artery in the mouth mimicking peritonsillar abscess.
AB  - The calculated incidence of aberrant internal carotid artery in the oropharynx is
      approximately 5% in the general population. An experienced otolaryngologist is
      not always available in general hospital; therefore, some invasive procedures in
      the oropharynx, such as aspiration, incision/drainage, and biopsy, which were
      performed for general infectious diseases or tissue diagnosis, may have resulted
      in fatal complication in these patients with misdiagnosis. We report a case to
      reveal that the awareness of such an anatomical variation before performing
      oropharyngeal procedures remains crucial.

PMID- 20159417
TI  - Management of a severe carbamazepine overdose with continuous venovenous
      hemodiafiltration.
AB  - Carbamazepine (CBZ) is a commonly used antiepileptic agent. Common toxic effects
      include neurological abnormalities; ataxia, seizures, coma, cardiorespiratory
      problems; dysrhythmias; conduction disorders; respiratory depression; and eye
      abnormalities, such as nystagmus and ophthalmoplegia. Carbamazepine is highly
      protein bound. There is no antidote for the medication. Carbamazepine is not
      removed effectively through conventional hemodialysis. Supportive measures and
      charcoal hemoperfusion have been regarded as efficient treatment methods. We
      herein report a 17-year old girl to whom continuous venovenous hemodiafiltration
      lacking the albumin-enhance after suicidal overdose of CBZ was performed. We
      suggest continuous venovenous hemodiafiltration lacking the albumin-enhance as an
      alternative emergency treatment modality for cases who had ingested CBZ in toxic
      levels.

PMID- 20159418
TI  - Necrotizing fasciitis causing severe myocardial dysfunction with ST-segment
      elevation in a young man.
AB  - Necrotizing fasciitis is a life-threatening infection of the fascia and
      subcutaneous tissues. We report on a 30-year-old man with history of
      intramuscular injection resulted in gluteal abscess that progressed to
      necrotizing fasciitis. On admission, the patient developed circulatory collapse,
      severe left ventricular dysfunction, and ST-segment elevation in the inferior
      leads. Wound and blood cultures indicated staphylococcal infection. The clinical,
      laboratory, echocardiographic, and electrocardiographic features are discussed.

PMID- 20159419
TI  - Queer consequence of cough: atrial myxoma embolization with acute occlusion of
      the abdominal aorta.
AB  - We introduce a rare case of sudden paraplegia preceded by vigorous coughing. This
      case demonstrates that detachment of a myxoma fragment can possibly be triggered
      by an abrupt increase in intrathoracic pressure. It is a potential complication
      that has never been reported in the literature. This case illustrates that
      clinicians should consider cardiac myxoma in a patient with an embolic event of
      ambiguous etiology, especially when the event is preceded by a forceful, valsalva
      maneuver-like action.

PMID- 20159420
TI  - Case report and review: Potts disease and epididymal tuberculosis presenting as
      back pain and scrotal mass.
AB  - Tuberculosis (TB) is the world's leading infectious disease killer after AIDS
      [Tubercle. 1991;72:1-6; Lancet. 2003;362(9387):887-899]. Vertebral TB is the most
      common form of skeletal TB [Spine. 1997; 22(15):1791-1797], whereas male genital
      TB is an uncommon form of extrapulmonary TB [Urol Clin North Am. 2003;30(1):111
      121]. We present the case of a man who presented to the emergency department with
      a history of acute on chronic back pain and an incidental scrotal mass. He was
      subsequently diagnosed with tuberculosis spondylitis (Potts disease) and
      epididymal tuberculosis. The epidemiology, clinical presentation, diagnosis, and
      treatment of tuberculosis spondylitis are discussed.

PMID- 20159421
TI  - Postpartum appendicitis manifesting as umbilical purulence.
AB  - The diagnosis of abdominal pain is often difficult in the intrapartum and
      postpartum states. We describe an unusual case of postpartum appendicitis
      complicated by appendiceal rupture, abscess formation, and enterocutaneous
      umbilical drainage.

PMID- 20159422
TI  - Child presenting to the ED with prolonged autonomic symptoms followed by
      generalized seizure activity.
AB  - A 5-year-old girl presented to the emergency department (ED) with a parental
      complaint of vomiting and seizure-like activity. The patient had been in her
      normal state of health before the onset of this activity and had had no recent
      illnesses. Shortly after the child had gone to bed, she awoke complaining of
      feeling sick to her stomach. Over several minutes the child became less
      responsive to questioning, followed by rightward eye and head deviation and
      vomiting. Following this, the child's eyes remained fixed in a rightward gaze and
      she was no longer responsive to questioning despite appearing awake. On the way
      to the hospital the child became flaccid, which was shortly followed by further
      vomiting and right upper extremity jerking and finally full upper extremity
      convulsive activity. In the ED, the child remained in this state for
      approximately 90 minutes despite the use of intravenous diazepam. Gradually, she
      became responsive to parental stimulation and questioning.

PMID- 20159423
TI  - [Perioperative care of patients taking vitamin K antagonists: register
      yourself!].

PMID- 20159424
TI  - Creatine and creatine deficiency syndromes: biochemical and clinical aspects.
AB  - Creatine deficiency syndromes, which have only recently been described, represent
      a group of inborn errors of creatine synthesis (L-arginine-glycine
      amidinotransferase deficiency and guanidinoacetate methyltransferase deficiency)
      and transport (creatine transporter deficiency). Patients with creatine
      deficiency syndromes present with mental retardation expressive speech and
      language delay, and epilepsy. Patients with guanidinoacetate methyltransferase
      deficiency or creatine transporter deficiency may exhibit autistic behavior. The
      common denominator of these disorders is the depletion of the brain creatine
      pool, as demonstrated by in vivo proton magnetic resonance spectroscopy. For
      diagnosis, laboratory investigations start with analysis of guanidinoacetate,
      creatine, and creatinine in plasma and urine. Based on these findings, enzyme
      assays or DNA mutation analysis may be performed. The creatine deficiency
      syndromes are underdiagnosed, so the possibility should be considered in all
      children affected by unexplained mental retardation, seizures, and speech delay.
      Guanidinoacetate methyltransferase deficiency and arginine-glycine
      amidinotransferase deficiency are treatable by oral creatine supplementation, but
      patients with creatine transporter deficiency do not respond to this type of
      treatment.

PMID- 20159425
TI  - Correlation between magnetic resonance imaging and histopathologic grades in
      Rasmussen syndrome.
AB  - The aim of this study was to investigate the correlation between magnetic
      resonance imaging (MRI) and histopathologic findings in Rasmussen syndrome.
      Serial MRIs were obtained for five patients who had histologically proven
      Rasmussen syndrome. The histopathologic grades of the lesions were subdivided
      into phases: active 1-3, resolving 1-3, and chronic inflammatory. The images were
      then correlated with histopathologic findings. Neuropathologic findings in the
      central areas on MRI demonstrated only the chronic and resolving grades, but
      active inflammatory abnormalities were present not only at the margins of the
      lesions, but also in areas of subtle signal abnormality on MRI. Atrophic areas on
      MRI exhibited all grades of histopathologic abnormalities, but chronic and
      resolving grades were predominant. Seizure duration of less than 6 months was
      associated with very active grades, duration of 1-2 years with variable grades,
      and duration greater than 6 years with chronic and resolving grades only. The MRI
      images correlated highly with histopathologic analysis. These findings suggest
      that the lesions initially arise from one site in the brain, and so support the
      centrifugal spreading theory of this disease. Findings also suggest that the
      margin rather than the center of the MRI abnormality may be the most ideal site
      for biopsy.

PMID- 20159426
TI  - CP or not CP? A review of diagnoses in a cerebral palsy register.
AB  - The purpose of this study was to document the inaccuracy rate of diagnosis of
      cerebral palsy recorded on the South Australian Cerebral Palsy Register. A total
      of 402 children born in South Australia from 1993 to 2002 and notified to the
      Register as having cerebral palsy were identified through the Register database,
      and 21 children (5.2%) were later identified to have a noncerebral palsy
      diagnosis. Of these, 5 had either a metabolic or a neurodegenerative disorder and
      2 had a syndromic disorder (1 Joubert syndrome and 1 Sotos syndrome); the
      remaining 14 children had one of the following final diagnoses: developmental
      delay, gross motor delay, perinatal myositis, spinal subdural and subarachnoid
      arteriovenous malformation, and Erb's palsy. In 16 of 21 children (76%), the
      diagnosis was changed at 5 years of age or older. Studies based on population
      registers may need to take into account the possibility of misclassification,
      estimated to be at least 5.2% in this study. A complete clinical assessment at
      the time of diagnosis followed by regular reassessment would enable the clinician
      to exclude children with alternative diagnoses, which has important implications
      for clinical management and research based on cerebral palsy registers.

PMID- 20159427
TI  - Association between prenatal stress and infantile spasms: a case-control study in
      China.
AB  - The present study investigated a possible correlation between prenatal stress and
      the onset of infantile spasms. A total of 120 infants (60 cases, 30 positive
      controls, and 30 negative controls) went through routine etiologic screening. The
      Pregnant Woman Life Event Scale was used to investigate and evaluate the degree
      of prenatal stress of the mothers in the three infant groups. Etiologic analyses
      indicated no statistical difference between the infantile spasms group and the
      other epilepsy control group. There was a significant difference in the degree of
      prenatal stress among mothers of the three infant groups, with higher maternal
      prenatal stress levels in the infantile spasms group than in the other epilepsy
      group (positive control) or the normal control group (P < 0.05). Regression
      analysis with the dummy variable indicated that the onset risk of infantile
      spasms correspondingly increased with the degree of maternal prenatal stress for
      stress levels 1-3 (out of four levels) (P < 0.05). Within a certain range, the
      onset risk of infantile spasms increases with the degree of prenatal stress.

PMID- 20159428
TI  - Cognitive effects of topiramate in migraine patients aged 12 through 17 years.
AB  - Neuropsychologic data are presented from a randomized, double-blind, placebo
      controlled, multicenter study with placebo, topiramate 50 mg/day, and topiramate
      100 mg/day. The Cambridge Neuropsychological Test Automated Battery (CANTAB) and
      cognitive adverse events were used to evaluate neurocognitive effects of
      topiramate. Topiramate 100 mg/day vs placebo was associated with slight
      statistically significant score increases, indicating slowing, from baseline vs
      placebo in three CANTAB measures: five-choice reaction time (P = 0.028), pattern
      recognition memory mean correct latency (P = 0.027), and rapid visual information
      processing mean latency (P = 0.040). No other patterns related to topiramate
      treatment were observed in measurements of learning, memory, and visual
      information processing, except for potential improvement with topiramate 100
      mg/day vs placebo in spatial span total errors (accuracy test) (P = 0.040). The
      most common cognitive and neuropsychiatric adverse events with a higher incidence
      in the topiramate 50 and 100 mg/day groups vs placebo were anorexia (9% and 11%
      vs 3%), insomnia (9% and 3% vs 3%), fatigue (6% and 9% vs 6%), and dizziness (6%
      and 9% vs 0%). Thus, topiramate 100 mg/day was associated with modest increases
      in psychomotor reaction times. Learning, memory, and executive function were
      unchanged. The tolerability profile, including cognitive adverse events, appeared
      to be acceptable.

PMID- 20159429
TI  - Value of brain magnetic resonance imaging in mitochondrial respiratory chain
      disorders.
AB  - Mitochondrial respiratory chain (MRC) disorders have variable clinical
      manifestations which are mainly neurologic. Diagnosis in children is more complex
      than in adults because the classic phenotype, ragged red fibers, and mtDNA
      mutations are rarely seen in children. Moreover, clinical manifestations of
      disease in developing brains are less explicit. Although not specific,
      neuroimaging may be contributory to the diagnosis of these disorders in pediatric
      patients. Brain magnetic resonance images were reviewed for 133 pediatric
      patients investigated for a MRC disorder at a single center over a period of 10
      years (1997-2006), in an attempt to identify distinctive neuroimaging features of
      MRC defects. Patients fit into four groups, according to the Bernier criteria:
      definite (63 cases), probable (53 cases), possible (7 cases) and unlikely
      diagnosis (10 cases). Brain atrophy (41 cases), supratentorial white matter
      lesions (14 cases), basal ganglia involvement (9 cases), and delayed myelination
      (9 cases) were the most frequent anomalies in the definite group, and 8 patients
      presented Leigh syndrome. Neuroimaging findings of the 63 children in the
      definite group were compared with the remainder and with those in the possible
      and unlikely groups. There were no significant differences in brain images
      between the groups analyzed, and therefore no distinctive brain imaging features
      were identified specific for MRC disorders.

PMID- 20159430
TI  - Cardiac arrhythmias and ictal events within an epilepsy monitoring unit.
AB  - The aim of this study was to determine the incidence and describe the factors
      influencing ictal cardiac arrhythmias in children with epilepsy. A 2-year review
      within a pediatric epilepsy monitoring unit revealed 2066 electrographically
      confirmed seizures in 139 patients. Demographic, seizure, and cardiac variables
      were collected for each patient. Fisher's exact test, Wilcoxon rank-sum test, and
      Spearman's rank correlation coefficient were used to identify significant
      differences and associations at the seizure and patient levels. In 244 seizures
      meeting inclusion criteria, ictal cardiac arrhythmias were seen in 45% of the
      seizures (40% of the patients). The most common arrhythmia was benign respiratory
      sinus arrhythmia (78% of seizures with arrhythmias, 70% of patients with
      arrhythmias). Potentially serious arrhythmias included irregular variable
      arrhythmias, and abnormal QRS intervals were seen in 12% of all the patients. In
      seizures with ictal arrhythmias, 64% occurred in male patients (P = 0.016) and
      78% occurred in white patients (P = 0.013). This study estimates the incidence of
      ictal arrhythmias within the pediatric population that need further medical
      attention and management.

PMID- 20159431
TI  - Paralytic syndromes in children: epidemiology and relationship to vaccination.
AB  - Acute flaccid paralysis is a standard outcome for detection of poliomyelitis
      globally and an ongoing potential vaccine-associated adverse event concern for
      polio, influenza, and meningococcal vaccines. No systematic population-based data
      on the epidemiologic and clinical features of this condition, or its potential
      association with immunization, have been reported from the United States. The
      present retrospective cohort study of acute flaccid paralysis in the Southern and
      Northern California Kaiser Permanente Health Care Plans was conducted using
      computerized diagnosis data and medical record review of potential cases among
      children aged 1 month to <15 years and diagnosed from January 1, 1992 through
      December 31, 1998. In all, 3297 potential cases were identified; of these, 2682
      cases (81%) did not meet the case definition, and of the remaining 615 cases, 245
      (7% of the total) were included. The incidence of disease was 1.4 per 100,000
      children/year (95% confidence interval = 1.2-1.6); predicting approximately 844
      children/year in the United States. Disease incidence did not vary with season or
      sex, varied inversely with age, and declined 28% during the study period. No
      cases of vaccine-associated acute flaccid paralysis were identified. In
      nonendemic countries, ongoing acute flaccid paralysis surveillance is often
      conducted, because of the risk of poliovirus importation, but this practice may
      be difficult to justify, given low disease incidence and breadth of clinical
      presentation.

PMID- 20159432
TI  - Anti-N-methyl-D-aspartate receptor encephalitis: early treatment is beneficial.
AB  - Anti-N-methyl-D-aspartate receptor antibody has been associated with a severe
      stereotypic form of subacute encephalitis, often found in women with ovarian
      teratoma. Reported here is the diagnosis of anti-N-methyl-D-aspartate receptor
      encephalitis in a 5-year-old girl who presented with subacute encephalopathy and
      movement disorder without evidence of malignancy. Early diagnosis and treatment
      with immune globulin and steroids resulted in near-complete recovery.

PMID- 20159433
TI  - Persistent focal seizures after cat scratch encephalopathy.
AB  - This report describes a 9-year-old child with status epilepticus and cat scratch
      disease. This patient's focal seizures and electroencephalographic changes
      persisted for 18 months after status epilepticus. This patient represents the
      third reported case of persistent focal seizures or electroencephalographic
      changes after status epilepticus secondary to cat scratch disease. This finding
      suggests that cat scratch encephalopathy may be a cause of localization-related
      epilepsy, and should be investigated when evaluating a patient with new-onset
      partial seizures.

PMID- 20159434
TI  - Intracerebral blood and MRS in neonatal nonketotic hyperglycinemia.
AB  - Nonketotic hyperglycinemia is an inborn error of glycine metabolism leading to
      the accumulation of glycine in the brain. The neonatal form presents in the first
      days after birth with encephalopathy, seizures. and characteristic "hiccups."
      Rapid progression can lead to intractable seizures, coma, and respiratory
      failure. The outcome is invariably poor, and many die before age 1 year. The
      diagnosis of nonketotic hyperglycinemia is traditionally based on the finding of
      a raised cerebrospinal fluid-to-plasma-glycine ratio. An elevated glycine peak,
      using long echo time proton magnetic resonance spectroscopy, is also specific to
      nonketotic hyperglycinemia. The presence of blood in a cerebrospinal fluid sample
      is known to render the glycine level uninterpretable. However, there have been no
      reports of intracerebral blood confounding the cerebral glycine detected on long
      echo time proton magnetic resonance spectroscopy. We report on an infant who
      presented with neonatal encephalopathy and imaging findings consistent with
      hypoxic-ischemic encephalopathy, as well as intracerebral hemorrhage and an
      abnormal glycine peak on spectroscopy. The source of the abnormal glycine on long
      echo time proton magnetic resonance spectroscopy was intracerebral blood,
      highlighting an important confounder in the interpretation of long echo time
      proton magnetic resonance spectroscopy in suspected nonketotic hyperglycinemia.

PMID- 20159435
TI  - Mucolipidosis type IV: a subtle pediatric neurodegenerative disorder.
AB  - The mucolipidoses are a heterogeneous group of autosomal recessive
      neurodegenerative lysosomal storage disorders. Mucolipidosis type IV is rare; it
      is seen predominantly in the Ashkenazi Jewish population and usually presents
      with global neurodevelopmental delays in infancy, subtle corneal opacifications
      or clouding, and very slowly progressive neurodegeneration over many years.
      Elevation of serum gastrin is reported; findings from x-rays of bone and joints
      and lysosomal studies are normal. Reported here are two cases of mucolipidosis
      type IV in children not of Ashkenazi Jewish origin who presented during infancy
      with nonspecific global psychomotor delays, generalized hypotonia, and mild
      corneal abnormalities, but remained undiagnosed for years. A rare gene mutation
      in MCOLN1 was confirmed in one of the two patients, in addition to abnormal serum
      gastrin levels. More striking was the length of time that these children eluded
      detection of their final diagnosis.

PMID- 20159436
TI  - A novel mutation in the SCO2 gene in a neonate with early-onset
      cardioencephalomyopathy.
AB  - Mutations in the SCO2 gene [SCO cytochrome oxidase deficient homolog 2 (yeast)]
      causing cytochrome c oxidase deficiency have been reported in at least in 26
      patients with fatal infantile cardioencephalomyopathy. Mutation 1541G > A
      affecting protein stability is associated with the majority of cases, and the
      other 11 described mutations have more serious deleterious structural
      consequences for the protein product. Reported here is a novel case caused by
      compound heterozygosity of SCO2. The child presented at the age of 3 weeks with
      failure-to-thrive, muscular hypotonia, hypertrophic cardiomyopathy, and lactic
      acidemia. Leigh syndrome was diagnosed based on magnetic resonance imaging
      findings. Immunohistochemical and enzymatic investigations on muscle indicated
      totally absent cytochrome c oxidase activity. Both parents had mild mental
      retardation. Sequence analysis in the patient and in his parents revealed
      heterozygous mutation c.418G > A in exon 2 inherited from the father and
      maternally inherited heterozygous insertion of 19bp at position 17 in the coding
      region of the SCO2 gene. Respiratory chain enzyme activity measurements indicated
      normal activity in both parents, although the mother's cytochrome c oxidase
      activity was lower. This gene may be involved in the etiology of the mother's
      mental retardation.

PMID- 20159437
TI  - Grade IV fetal intracranial hemorrhage with good cognitive function.
AB  - Fewer than 200 cases of prenatally diagnosed magnetic resonance imaging-confirmed
      fetal intracranial hemorrhage have been reported. Children surviving grade IV
      fetal intracranial hemorrhage usually manifest severe impairments, including
      mental retardation. We report on a child with a grade IV intracranial hemorrhage
      diagnosed by in utero ultrasound at 28 weeks of gestation, and confirmed by fetal
      magnetic resonance imaging at 29 weeks of gestation. At age 27 months, she has a
      ventriculoperitoneal shunt and exhibits hemiplegic cerebral palsy, but without
      seizures, and with normal cognitive function and excellent verbal ability. We
      discuss how perinatal care may have contributed to her good outcome.

PMID- 20159438
TI  - Diaphragmatic paralysis associated with neonatal brachial plexus palsy.
AB  - Phrenic nerve palsy can occur in the context of neonatal brachial plexus palsy,
      yet neither outcomes nor definitive treatment guidelines have been established.
      Diaphragmatic paralysis alone in the newborn results in significant respiratory
      sequelae and failure to thrive. Reviewing the available literature revealed
      little information about the incidence of phrenic nerve palsy associated with
      neonatal brachial plexus palsy, or whether outcomes are associated with the
      severity of the brachial plexus palsy. Of patients with brachial plexus palsy
      evaluated during 2005-2009 (n = 166) at our institution, a minority (2.4%; n = 4)
      had clinically significant diaphragmatic palsy. Of these, a majority (75%; n = 3)
      manifested respiratory complications sufficient to warrant diaphragmatic
      plication. The severity of brachial plexus palsy failed to correlate with
      severity of respiratory consequences. None of the patients underwent nerve repair
      or reconstruction. We suggest that diaphragmatic paralysis should not be
      overlooked during a brachial plexus examination, and diaphragmatic paralysis in
      the very young may require aggressive intervention before the treatment of
      brachial plexus palsy.

PMID- 20159439
TI  - Rolandic epilepsy.

PMID- 20159441
TI  - Identification of the synthetic pathway producing the endocannabinoid that
      mediates the bulk of retrograde signaling in the brain.
AB  - Endocannabinoids serve as retrograde messengers that are released by postsynaptic
      cells to regulate neurotransmitter release from presynaptic boutons. A new study
      in this issue of Neuron by Tanimura et al. establishes that most endocannabinoid
      signaling in the brain is a consequence of the calcium-dependent or receptor
      driven generation of the retrograde signal 2-arachidonoylglycerol (2-AG) by
      diacylglycerol lipase alpha (DGLalpha).

PMID- 20159442
TI  - Nedd4 branches out.
AB  - The branching of dendrites and axons is a key determinant of neural circuit
      formation. In this issue of Neuron, Kawabe et al. demonstrate that the ubiquitin
      ligase Nedd4 promotes the branching of developing dendrites by targeting the
      small G protein Rap2. In a complementary study, Drinjakovic et al. show that
      Nedd4 promotes the branching of developing axons by ubiquitinating a different
      target, the phosphatase PTEN.

PMID- 20159443
TI  - Linking local circuit inhibition to olfactory behavior: a critical role for
      granule cells in olfactory discrimination.
AB  - In this issue of Neuron, Abraham et al. report a direct connection between
      inhibitory function and olfactory behavior. Using molecular methods to alter
      glutamate receptor subunit composition in olfactory bulb granule cells, the
      authors found a selective modulation in the time required for difficult, but not
      simple, olfactory discrimination tasks.

PMID- 20159445
TI  - The spiritual brain: selective cortical lesions modulate human self
      transcendence.
AB  - The predisposition of human beings toward spiritual feeling, thinking, and
      behaviors is measured by a supposedly stable personality trait called self
      transcendence. Although a few neuroimaging studies suggest that neural activation
      of a large fronto-parieto-temporal network may underpin a variety of spiritual
      experiences, information on the causative link between such a network and
      spirituality is lacking. Combining pre- and post-neurosurgery personality
      assessment with advanced brain-lesion mapping techniques, we found that selective
      damage to left and right inferior posterior parietal regions induced a specific
      increase of self-transcendence. Therefore, modifications of neural activity in
      temporoparietal areas may induce unusually fast modulations of a stable
      personality trait related to transcendental self-referential awareness. These
      results hint at the active, crucial role of left and right parietal systems in
      determining self-transcendence and cast new light on the neurobiological bases of
      altered spiritual and religious attitudes and behaviors in neurological and
      mental disorders.

PMID- 20159444
TI  - Imaging the human medial temporal lobe with high-resolution fMRI.
AB  - High-resolution functional MRI (hr-fMRI) affords unique leverage on the
      functional properties of human medial temporal lobe (MTL) substructures. We
      review initial hr-fMRI efforts to delineate (1) encoding and retrieval processes
      within the hippocampal circuit, (2) hippocampal subfield contributions to pattern
      separation and pattern completion, and (3) the representational capabilities of
      distinct MTL subregions. Extant data reveal functional heterogeneity within human
      MTL and highlight the promise of hr-fMRI for bridging human, animal, and
      computational approaches to understanding MTL function.

PMID- 20159446
TI  - The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase
      alpha mediates retrograde suppression of synaptic transmission.
AB  - Endocannabinoids are released from postsynaptic neurons and cause retrograde
      suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2
      AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG
      contributes to retrograde signaling, we generated and analyzed mutant mice
      lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase alpha
      (DGLalpha) and beta (DGLbeta). We found that endocannabinoid-mediated retrograde
      synaptic suppression was totally absent in the cerebellum, hippocampus, and
      striatum of DGLalpha knockout mice, whereas the retrograde suppression was intact
      in DGLbeta knockout brains. The basal 2-AG content was markedly reduced and
      stimulus-induced elevation of 2-AG was absent in DGLalpha knockout brains,
      whereas the 2-AG content was normal in DGLbeta knockout brains. Morphology of the
      brain and expression of molecules required for 2-AG production other than DGLs
      were normal in the two knockout mice. We conclude that 2-AG produced by DGLalpha,
      but not by DGLbeta, mediates retrograde suppression at central synapses.

PMID- 20159447
TI  - Sonic hedgehog signaling confers ventral telencephalic progenitors with distinct
      cortical interneuron fates.
AB  - Interneurons in the cerebral cortex regulate cortical functions through the
      actions of distinct subgroups that express parvalbumin, somatostatin, or
      calretinin. The genesis of the first two subgroups requires the expression of
      NKX2.1, which is maintained by SHH signaling during neurogenesis. In this paper,
      we report that mosaic elimination in the medial ganglionic eminence (MGE) of Smo,
      a key effector of SHH signaling, reveals that MGE progenitors retain a remarkable
      degree of plasticity during the neurogenic period. SHH signaling prevents the
      upregulation of GSX2 and conversion of some MGE progenitors to a caudal
      ganglionic eminence-like, bipolar calretinin-expressing cell fate that is
      promoted by GSX2. In addition, a higher level of SHH signaling promotes the
      generation of the somatostatin-expressing interneuron at the expense of
      parvalbumin-expressing subgroup. These results indicate that cortical interneuron
      diversity, a major determinant of cortical function, is critically influenced by
      differential levels of SHH signaling within the ventral telencephalon.

PMID- 20159448
TI  - E3 ligase Nedd4 promotes axon branching by downregulating PTEN.
AB  - Regulated protein degradation via the ubiquitin-proteasome system (UPS) plays a
      central role in building synaptic connections, yet little is known about either
      which specific UPS components are involved or UPS targets in neurons. We report
      that inhibiting the UPS in developing Xenopus retinal ganglion cells (RGCs) with
      a dominant-negative ubiquitin mutant decreases terminal branching in the tectum
      but does not affect long-range navigation to the tectum. We identify Nedd4 as a
      prominently expressed E3 ligase in RGC axon growth cones and show that disrupting
      its function severely inhibits terminal branching. We further demonstrate that
      PTEN, a negative regulator of the PI3K pathway, is a key downstream target of
      Nedd4: not only does Nedd4 regulate PTEN levels in RGC growth cones, but also,
      the decrease of PTEN rescues the branching defect caused by Nedd4 inhibition.
      Together our data suggest that Nedd4-regulated PTEN is a key regulator of
      terminal arborization in vivo.

PMID- 20159449
TI  - Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development.
AB  - Nedd4-1 is a "neuronal precursor cell expressed and developmentally downregulated
      protein" and among the most abundant E3 ubiquitin ligases in mammalian neurons.
      In analyses of conventional and conditional Nedd4-1-deficient mice, we found that
      Nedd4-1 plays a critical role in dendrite formation. Nedd4-1, the
      serine/threonine kinase TNIK, and Rap2A form a complex that controls Nedd4-1
      mediated ubiquitination of Rap2A. Ubiquitination by Nedd4-1 inhibits Rap2A
      function, which reduces the activity of Rap2 effector kinases of the TNIK family
      and promotes dendrite growth. We conclude that a Nedd4-1/Rap2A/TNIK signaling
      pathway regulates neurite growth and arborization in mammalian neurons.

PMID- 20159450
TI  - Regulation of synaptic structure and function by FMRP-associated microRNAs miR
      125b and miR-132.
AB  - MicroRNAs (miRNAs) are noncoding RNAs that suppress translation of specific
      mRNAs. The miRNA machinery interacts with fragile X mental retardation protein
      (FMRP), which functions as translational repressor. We show that miR-125b and miR
      132, as well as several other miRNAs, are associated with FMRP in mouse brain.
      miR-125b and miR-132 had largely opposing effects on dendritic spine morphology
      and synaptic physiology in hippocampal neurons. FMRP knockdown ameliorates the
      effect of miRNA overexpression on spine morphology. We identified NMDA receptor
      subunit NR2A as a target of miR-125b and show that NR2A mRNA is specifically
      associated with FMRP in brain. In hippocampal neurons, NR2A expression is
      negatively regulated through its 3' UTR by FMRP, miR-125b, and Argonaute 1.
      Regulation of NR2A 3'UTR by FMRP depends in part on miR-125b. Because NMDA
      receptor subunit composition profoundly affects synaptic plasticity, these
      observations have implications for the pathophysiology of fragile X syndrome, in
      which plasticity is altered.

PMID- 20159452
TI  - Synaptic inhibition in the olfactory bulb accelerates odor discrimination in
      mice.
AB  - Local inhibitory circuits are thought to shape neuronal information processing in
      the central nervous system, but it remains unclear how specific properties of
      inhibitory neuronal interactions translate into behavioral performance. In the
      olfactory bulb, inhibition of mitral/tufted cells via granule cells may
      contribute to odor discrimination behavior by refining neuronal representations
      of odors. Here we show that selective deletion of the AMPA receptor subunit GluA2
      in granule cells boosted synaptic Ca(2+) influx, increasing inhibition of mitral
      cells. On a behavioral level, discrimination of similar odor mixtures was
      accelerated while leaving learning and memory unaffected. In contrast, selective
      removal of NMDA receptors in granule cells slowed discrimination of similar
      odors. Our results demonstrate that inhibition of mitral cells controlled by
      granule cell glutamate receptors results in fast and accurate discrimination of
      similar odors. Thus, spatiotemporally defined molecular perturbations of
      olfactory bulb granule cells directly link stimulus similarity, neuronal
      processing time, and discrimination behavior to synaptic inhibition.

PMID- 20159451
TI  - Critical period plasticity is disrupted in the barrel cortex of FMR1 knockout
      mice.
AB  - Alterations in sensory processing constitute prominent symptoms of fragile X
      syndrome; however, little is known about how disrupted synaptic and circuit
      development in sensory cortex contributes to these deficits. To investigate how
      the loss of fragile X mental retardation protein (FMRP) impacts the development
      of cortical synapses, we examined excitatory thalamocortical synapses in
      somatosensory cortex during the perinatal critical period in Fmr1 knockout mice.
      FMRP ablation resulted in dysregulation of glutamatergic signaling maturation.
      The fraction of silent synapses persisting to later developmental times was
      increased; there was a temporal delay in the window for synaptic plasticity,
      while other forms of developmental plasticity were not altered in Fmr1 knockout
      mice. Our results indicate that FMRP is required for the normal developmental
      progression of synaptic maturation, and loss of this important RNA binding
      protein impacts the timing of the critical period for layer IV synaptic
      plasticity.

PMID- 20159453
TI  - Nonoverlapping sets of synapses drive on responses and off responses in auditory
      cortex.
AB  - Neurons in visual, somatosensory, and auditory cortex can respond to the
      termination as well as the onset of a sensory stimulus. In auditory cortex, these
      off responses may underlie the ability of the auditory system to use sound
      offsets as cues for perceptual grouping. Off responses have been widely proposed
      to arise from postinhibitory rebound, but this hypothesis has never been directly
      tested. We used in vivo whole-cell recordings to measure the synaptic inhibition
      evoked by sound onset. We find that inhibition is invariably transient,
      indicating that off responses are not caused by postinhibitory rebound in
      auditory cortical neurons. Instead, on and off responses appear to be driven by
      distinct sets of synapses, because they have distinct frequency tuning and
      different excitatory-inhibitory balance. Furthermore, an on-on sequence causes
      complete forward suppression, whereas an off-on sequence causes no suppression at
      all. We conclude that on and off responses are driven by largely nonoverlapping
      sets of synaptic inputs.

PMID- 20159454
TI  - Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving
      mice.
AB  - Computations in cortical circuits are mediated by synaptic interactions between
      excitatory and inhibitory neurons, and yet we know little about their activity in
      awake animals. Here, through single and dual whole-cell recordings combined with
      two-photon microscopy in the barrel cortex of behaving mice, we directly compare
      the synaptically driven membrane potential dynamics of inhibitory and excitatory
      layer 2/3 neurons. We find that inhibitory neurons depolarize synchronously with
      excitatory neurons, but they are much more active with differential contributions
      of two classes of inhibitory neurons during different brain states. Fast-spiking
      GABAergic neurons dominate during quiet wakefulness, but during active
      wakefulness Non-fast-spiking GABAergic neurons depolarize, firing action
      potentials at increased rates. Sparse uncorrelated action potential firing in
      excitatory neurons is driven by fast, large, and cell-specific depolarization. In
      contrast, inhibitory neurons fire correlated action potentials at much higher
      frequencies driven by slower, smaller, and broadly synchronized depolarization.

PMID- 20159455
TI  - Pre-operative breast MRI in women with recently diagnosed breast cancer--where to
      next?

PMID- 20159456
TI  - Overview of the role of pre-operative breast MRI in the absence of evidence on
      patient outcomes.
AB  - The role of pre-operative breast MRI is outlined on the basis of the existing
      evidence in favor of a superior capability in comparison with mammography and
      sonography to detect ipsilateral and contralateral malignant lesions and to
      evaluate the disease extent, including the extensive intraductal component
      associated with invasive cancers. Patients with a potential higher anticipated
      benefit from pre-operative MRI can be identified as those: with mammographically
      dense breasts; with a unilateral multifocal/multicentric cancer or a synchronous
      bilateral cancer already diagnosed at mammography and sonography; with a lobular
      invasive cancer; at high-risk for breast cancer; with a cancer which shows a
      discrepancy in size of >1 cm between mammography and sonography; or under
      consideration for partial breast irradiation. More limited evidence exists in
      favor of MRI for evaluating candidates for total skin sparing mastectomy or for
      patients with Paget's disease. Irrespective of whether the clinical team
      routinely uses preoperative MRI or not: women newly diagnosed with breast cancer
      should always be informed of the potential risks and benefits of pre-operative
      MRI; results of pre-operative MRI should be interpreted taking into account
      clinical breast examination, mammography, sonography and verified by percutaneous
      biopsy; MRI-only detected lesions require MR-guidance for needle biopsy and pre
      surgical localization, and these should be available or potentially accessible if
      pre-operative MRI is to be implemented; total therapy delay due to pre-operative
      MRI (including MRI-induced work-up) should not exceed one month; changes in
      therapy planning resulting from pre-operative MRI should be decided by a
      multidisciplinary team.

PMID- 20159457
TI  - Counterview: Pre-operative breast MRI (magnetic resonance imaging) is not
      recommended for all patients with newly diagnosed breast cancer.
AB  - For the woman with a newly diagnosed early stage breast cancer, the routine use
      of pre-operative breast MRI (magnetic resonance imaging) is not indicated beyond
      conventional breast imaging (i.e., mammography with correlation ultrasound as
      indicated). There is no consistent evidence that a pre-operative breast MRI
      confers a benefit to the patient by improving clinical outcomes or surgical
      procedures. In a meta-analysis of studies reporting on the use of pre-operative
      breast MRI for the patient with an established index cancer, multifocal or
      multicentric disease was found on breast MRI in 16% of the patients, a rate
      substantially higher than the rate of local recurrence after breast conserving
      surgery plus definitive radiation treatment. In the largest retrospective study
      of patients treated with breast conserving surgery plus radiation, no gain was
      found for adding a breast MRI to conventional breast imaging. No randomized
      clinical trial has been designed to evaluate long term clinical outcomes
      associated with adding a pre-operative breast MRI. Adding pre-operative breast
      MRI can alter clinical management in ways that are potentially harmful to
      patients, for example, increased ipsilateral mastectomies, increased
      contralateral prophylactic mastectomies, increased work-ups, and delay to
      definitive surgery. In summary, the routine use of pre-operative breast MRI is
      not warranted for the typical patient with a newly diagnosed early stage breast
      cancer.

PMID- 20159458
TI  - Pre-operative MRI for women with newly diagnosed breast cancer: perspectives on
      clinician and patient decision-making when evidence is uncertain.
AB  - The routine use of pre-operative MRI in women with newly diagnosed breast cancer
      highlights the complexities of the use of new technology when evidence of benefit
      is uncertain. There are both potential harms and benefits. In the short term
      patients may desire and feel reassured by further testing and the use of new
      diagnostic techniques. However, they may also experience greater anxiety and
      distress from further tests and related follow-up procedures such as biopsy. In
      the long term MRI may result in more radical treatment decisions which are
      associated with poorer quality of life for women. Both patients and clinicians
      often (wrongly) assume that more information via testing leads to better outcomes
      (information bias). So how should pre-operative MRI be integrated into breast
      cancer care? First women need to be made aware of the uncertain evidence
      surrounding MRI. However whether it is appropriate to burden women with complex
      information and yet another decision at a time of high vulnerability and
      emotional distress should be considered. One potential solution is to use a
      Community Informed Consent approach in which a representative sample of patients
      and healthy women are educated about the benefits and harms and give their
      informed opinion about whether pre-operative MRI should be offered. Another
      approach is to provide patients with an evidence based decision aid to support
      individual informed choice. Either or a combination of both approaches would be
      acceptable and should be investigated. At present women are poorly informed about
      pre operative MRI and it is likely that they assume outcomes are be improved as a
      result. Clear communication about the limits of MRI to patients is needed
      alongside randomised trials to provide the evidence that benefit indeed outweighs
      the harms so that all parties involved may be comprehensively informed.

PMID- 20159459
TI  - Werner helicase wings DNA binding.
AB  - In this issue of Structure, Kitano et al. describe the structure of the DNA-bound
      winged-helix domain from the Werner helicase. This structure of a RecQ/DNA
      complex offers insights into the DNA-unwinding mechanisms of RecQ family
      helicases.

PMID- 20159460
TI  - TPR motifs: hallmarks of a new polysaccharide export scaffold.
AB  - Bacteria produce a remarkable range of surface and secreted polysaccharides. Two
      pathways have been defined for the biosynthesis and export of capsular
      polysaccharides and exopolysaccharides in Gram-negative bacteria. A structure of
      AlgK described in this issue provides structural insight into a third previously
      unrecognized pathway associated with important biopolymers (Keiski et al., 2010).

PMID- 20159461
TI  - Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and
      selectivity.
AB  - A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase
      (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the
      dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA
      with high affinity. Here we have determined the structures of the RIalpha D/D
      domain alone and in complex with D-AKAP2. The D/D domain presents an extensive
      surface for binding through a well-formed N-terminal helix, and this surface
      restricts the diversity of AKAPs that can interact. The structures also
      underscore the importance of a redox-sensitive disulfide in affecting AKAP
      binding. An unexpected shift in the helical register of D-AKAP2 compared to the
      RIIalpha:D-AKAP2 complex structure makes the mode of binding to RIalpha novel.
      Finally, the comparison allows us to deduce a molecular explanation for the
      sequence and spatial determinants of AKAP specificity.

PMID- 20159462
TI  - Comparison of the structures and peptide binding specificities of the BRCT
      domains of MDC1 and BRCA1.
AB  - The tandem BRCT domains of BRCA1 and MDC1 facilitate protein signaling at DNA
      damage foci through specific interactions with serine-phosphorylated protein
      partners. The MDC1 BRCT binds pSer-Gln-Glu-Tyr-COO(-) at the C terminus of the
      histone variant gammaH2AX via direct recognition of the C-terminal carboxylate,
      while BRCA1 recognizes pSer-X-X-Phe motifs either at C-terminal or internal sites
      within target proteins. Using fluorescence polarization binding assays, we show
      that while both BRCTs prefer a free main chain carboxylate at the +3 position,
      this preference is much more pronounced in MDC1. Crystal structures of BRCA1 and
      MDC1 bound to tetrapeptide substrates reveal differences in the environment of
      conserved arginines (Arg1699 in BRCA1 and Arg1933 in MDC1) that determine the
      relative affinity for peptides with -COO(-) versus -CO-NH(2) termini. A mutation
      in MDC1 that induces a more BRCA1-like conformation relaxes the binding
      specificity, allowing the mutant to bind phosphopeptides lacking a -COO(-)
      terminus.

PMID- 20159463
TI  - Structural basis for DNA strand separation by the unconventional winged-helix
      domain of RecQ helicase WRN.
AB  - The RecQ family of DNA helicases including WRN (Werner syndrome protein) and BLM
      (Bloom syndrome protein) protects the genome against deleterious changes. Here we
      report the cocrystal structure of the RecQ C-terminal (RQC) domain of human WRN
      bound to a DNA duplex. In the complex, the RQC domain specifically interacted
      with a blunt end of the duplex and, surprisingly, unpaired a Watson-Crick base
      pair in the absence of an ATPase domain. The beta wing, an extended hairpin motif
      that is characteristic of winged-helix motifs, was used as a "separating knife"
      to wedge between the first and second base pairs, whereas the recognition helix,
      a principal component of helix-turn-helix motifs that are usually embedded within
      DNA grooves, was unprecedentedly excluded from the interaction. Our results
      demonstrate a function of the winged-helix motif central to the helicase
      reaction, establishing the first structural paradigm concerning the DNA structure
      specific activities of the RecQ helicases.

PMID- 20159464
TI  - The structural basis of peptide-protein binding strategies.
AB  - Peptide-protein interactions are very prevalent, mediating key processes such as
      signal transduction and protein trafficking. How can peptides overcome the
      entropic cost involved in switching from an unstructured, flexible peptide to a
      rigid, well-defined bound structure? A structure-based analysis of peptide
      protein interactions unravels that most peptides do not induce conformational
      changes on their partner upon binding, thus minimizing the entropic cost of
      binding. Furthermore, peptides display interfaces that are better packed than
      protein-protein interfaces and contain significantly more hydrogen bonds, mainly
      those involving the peptide backbone. Additionally, "hot spot" residues
      contribute most of the binding energy. Finally, peptides tend to bind in the
      largest pockets available on the protein surface. Our study is based on peptiDB,
      a new and comprehensive data set of 103 high-resolution peptide-protein complex
      structures. In addition to improved understanding of peptide-protein
      interactions, our findings have direct implications for the structural modeling,
      design, and manipulation of these interactions.

PMID- 20159465
TI  - SusG: a unique cell-membrane-associated alpha-amylase from a prominent human gut
      symbiont targets complex starch molecules.
AB  - SusG is an alpha-amylase and part of a large protein complex on the outer surface
      of the bacterial cell and plays a major role in carbohydrate acquisition by the
      animal gut microbiota. Presented here, the atomic structure of SusG has an
      unusual extended, bilobed structure composed of amylase at one end and an
      unprecedented internal carbohydrate-binding motif at the other. Structural
      studies further demonstrate that the carbohydrate-binding motif binds
      maltooligosaccharide distal to, and on the opposite side of, the amylase
      catalytic site. SusG has an additional starch-binding site on the amylase domain
      immediately adjacent to the active cleft. Mutagenesis analysis demonstrates that
      these two additional starch-binding sites appear to play a role in catabolism of
      insoluble starch. However, elimination of these sites has only a limited effect,
      suggesting that they may have a more important role in product exchange with
      other Sus components.

PMID- 20159466
TI  - Structure of the Saccharomyces cerevisiae Cet1-Ceg1 mRNA capping apparatus.
AB  - The 5' guanine-N7 cap is the first cotranscriptional modification of messenger
      RNA. In Saccharomyces cerevisiae, the first two steps in capping are catalyzed by
      the RNA triphosphatase Cet1 and RNA guanylyltransferase Ceg1, which form a
      complex that is directly recruited to phosphorylated RNA polymerase II (RNAP
      IIo), primarily via contacts between RNAP IIo and Ceg1. A 3.0 A crystal structure
      of Cet1-Ceg1 revealed a 176 kDa heterotetrameric complex composed of one Cet1
      homodimer that associates with two Ceg1 molecules via interactions between the
      Ceg1 oligonucleotide binding domain and an extended Cet1 WAQKW amino acid motif.
      The WAQKW motif is followed by a flexible linker that would allow Ceg1 to achieve
      conformational changes required for capping while maintaining interactions with
      both Cet1 and RNAP IIo. The impact of mutations as assessed through genetic
      analysis in S. cerevisiae is consonant with contacts observed in the Cet1-Ceg1
      structure.

PMID- 20159467
TI  - Crystal structure of a Legionella pneumophila ecto -triphosphate
      diphosphohydrolase, a structural and functional homolog of the eukaryotic
      NTPDases.
AB  - Many pathogenic bacteria have sophisticated mechanisms to interfere with the
      mammalian immune response. These include the disruption of host extracellular ATP
      levels that, in humans, is tightly regulated by the nucleoside triphosphate
      diphosphohydrolase family (NTPDases). NTPDases are found almost exclusively in
      eukaryotes, the notable exception being their presence in some pathogenic
      prokaryotes. To address the function of bacterial NTPDases, we describe the
      structures of an NTPDase from the pathogen Legionella pneumophila
      (Lpg1905/Lp1NTPDase) in its apo state and in complex with the ATP analog AMPPNP
      and the subtype-specific NTPDase inhibitor ARL 67156. Lp1NTPDase is structurally
      and catalytically related to eukaryotic NTPDases and the structure provides a
      basis for NTPDase-specific inhibition. Furthermore, we demonstrate that the
      activity of Lp1NTPDase correlates directly with intracellular replication of
      Legionella within macrophages. Collectively, these findings provide insight into
      the mechanism of this enzyme and highlight its role in host-pathogen
      interactions.

PMID- 20159468
TI  - Structural interactions between collagen and proteoglycans are elucidated by
      three-dimensional electron tomography of bovine cornea.
AB  - Interactions between collagens and proteoglycans help define the structure and
      function of extracellular matrices. The cornea, which contains proteoglycans with
      keratan sulphate or chondroitin/dermatan sulphate glycosaminoglycan chains, is an
      excellent model system in which to study collagen-proteoglycan structures and
      interactions. Here, we present the first three-dimensional electron microscopic
      reconstructions of the cornea, and these include corneas from which
      glycosaminoglycans have been selectively removed by enzymatic digestion. Our
      reconstructions show that narrow collagen fibrils associate with sulphated
      proteoglycans that appear as extended, variable-length linear structures. The
      proteoglycan network appears to tether two or more collagen fibrils, and thus
      organize the matrix with enough spatial specificity to fulfill the requirements
      for corneal transparency. Based on the data, we propose that the characteristic
      pseudohexagonal fibril arrangement in cornea is controlled by the balance of a
      repulsive force arising from osmotic pressure and an attractive force due to the
      thermal motion of the proteoglycans.

PMID- 20159469
TI  - Crystal structure of the p53 core domain bound to a full consensus site as a self
      assembled tetramer.
AB  - Recent studies suggest that p53 binds predominantly to consensus sites composed
      of two decameric half-sites with zero spacing in vivo. Here we report the crystal
      structure of the p53 core domain bound to a full consensus site as a tetramer at
      2.13A resolution. Comparison with previously reported structures of p53 dimer:DNA
      complexes and a chemically trapped p53 tetramer:DNA complex reveals that DNA
      binding by the p53 core domain is a cooperative self-assembling process
      accompanied by structural changes of the p53 dimer and DNA. Each p53 monomer
      interacts with its two neighboring subunits through two different protein-protein
      interfaces. The DNA is largely B-form and shows no discernible bend, but the
      central base-pairs between the two half-sites display a significant slide. The
      extensive protein-protein and protein-DNA interactions explain the high
      cooperativity and kinetic stability of p53 binding to contiguous decameric sites
      and the conservation of such binding-site configuration in vivo.

PMID- 20159470
TI  - Direct observation of distinct A/P hybrid-state tRNAs in translocating ribosomes.
AB  - Transfer RNAs (tRNAs) link the genetic code in the form of messenger RNA (mRNA)
      to protein sequence. Translocation of tRNAs through the ribosome from aminoacyl
      (A) site to peptidyl (P) site and from P site to exit site is catalyzed in
      eukaryotes by the translocase elongation factor 2 (EF-2) and in prokaryotes by
      its homolog EF-G. During tRNA movement one or more "hybrid" states (A/P) is
      occupied, but molecular details of them and of the translocation process are
      limited. Here we show by cryo-electron microscopy that a population of mammalian
      ribosomes stalled at an mRNA pseudoknot structure contains structurally distorted
      tRNAs in two different A/P hybrid states. In one (A/P'), the tRNA is in contact
      with the translocase EF-2, which induces it. In the other (A/P''), the
      translocase is absent. The existence of these alternative A/P intermediate states
      has relevance to our understanding of the mechanics and kinetics of
      translocation.

PMID- 20159472
TI  - Clinical innovation and technology in craniomaxillofacial surgery. Preface.

PMID- 20159473
TI  - Outcomes research and the challenge of evidence-based surgery.
AB  - Outcomes research is focused on measuring the results or end products of health
      care interventions, processes, and practices. Data derived from outcomes research
      informs clinical practice, quality assurance, and patient safety activities, and
      can be the nidus for hypothesis-driven, patient-oriented research. This article
      introduces a definition of outcomes research, reviews how outcomes research may
      guide evidence-based surgical practice and health care processes, and reviews a
      model for outcomes research.

PMID- 20159471
TI  - AlgK is a TPR-containing protein and the periplasmic component of a novel
      exopolysaccharide secretin.
AB  - The opportunistic pathogen Pseudomonas aeruginosa causes chronic biofilm
      infections in cystic fibrosis patients. During colonization of the lung, P.
      aeruginosa converts to a mucoid phenotype characterized by overproduction of the
      exopolysaccharide alginate. Here we show that AlgK, a protein essential for
      production of high molecular weight alginate, is an outer membrane lipoprotein
      that contributes to the correct localization of the porin AlgE. Our 2.5 A
      structure shows AlgK is composed of 9.5 tetratricopeptide-like repeats, and three
      putative sites of protein-protein interaction have been identified.
      Bioinformatics analysis suggests that BcsA, PgaA, and PelB, involved in the
      production and export of cellulose, poly-beta-1,6-N-Acetyl-D-glucosamine, and Pel
      exopolysaccharide, respectively, share the same topology as AlgK/E. Together, our
      data suggest that AlgK plays a role in the assembly of the alginate biosynthetic
      complex and represents the periplasmic component of a new type of outer membrane
      secretin that differs from canonical bacterial capsular polysaccharide secretion
      systems.

PMID- 20159474
TI  - Prenatal diagnosis and treatment of craniomaxillofacial anomalies.
AB  - Many advances in health care are built on the evolution of technology. An
      entirely new patient has emerged in fetal medicine, with these advances in
      prenatal imaging allowing one to see and diagnose disease not previously
      appreciated. Clinicians can better plan for the delivery of the neonate, with
      identified anomalies being optimally managed and the impact on the neonate's
      health minimized. The oral and maxillofacial surgeon offers expertise in the
      management of craniomaxillofacial anomalies, including congenital tumors, facial
      clefts, craniosynostosis, micrognathia, and other congenital abnormalities. The
      techniques for perinatal care of the patient with craniofacial abnormalities
      continue to evolve as the technology improves. The authors describe their
      experience and some of the more common abnormalities with their management
      considerations that may be encountered by the oral and maxillofacial surgeon on
      the fetal diagnosis and treatment team.

PMID- 20159475
TI  - Bone morphogenetic proteins in craniomaxillofacial surgery.
AB  - Craniomaxillofacial surgery has many indications for bone regeneration and
      augmentation, ranging from socket preservation to reconstruction of large
      skeletal defects. The discovery of bone morphogenetic proteins (BMPs) as
      osteoinductive agents and the subsequent development of commercially available
      recombinant forms of BMPs have offered the potential to replace traditional
      grafting techniques with de novo bone formation. Extensive preclinical and
      clinical research has focused on establishing the safety and efficacy of using
      recombinant BMPs to regenerate bone in the facial skeleton. This article reviews
      the development and current scientific basis behind the use of these new
      biologics.

PMID- 20159476
TI  - Regenerative medicine for craniomaxillofacial surgery.
AB  - Regenerative medicine has recently seen much activity in basic and translational
      research. These advances are now making their way into surgical practice. A
      convergence of technologies has afforded opportunities previously not available
      with conventional surgical reconstructive techniques. Patients requiring complex
      reconstructive surgery in the craniomaxillofacial region typically benefit from
      local or regional flaps, nonvascularized grafts, microvascular tissue transfer,
      or substitute alloplastic materials to restore function and form. In these
      clinical situations, grafting procedures or alloplastic substitute materials
      provide best-case replacements for resected, injured, or congenitally missing
      tissues. However, ideal reconstructive goals, such as a complete return to
      original form and function, are frequently not completely achieved. Regenerative
      techniques now in clinical use and at the translational research stage hold
      promise for custom-tailored constructs with the potential to regenerate tissue in
      the host without significant donor site morbidity. These techniques may provide
      better structure, aesthetics, and function than the best currently available
      options. This article presents the latest concepts in craniomaxillofacial
      regenerative medicine and reviews the multipronged approach to restoring
      architecture using novel "smart" multifunctional scaffolds, cellular
      technologies, growth factors, and other novel regenerative medical strategies.

PMID- 20159477
TI  - Cleft lip and palate surgery: an update of clinical outcomes for primary repair.
AB  - The comprehensive management of cleft lip and palate has received significant
      attention in the surgical literature over the last half century. It is the most
      common congenital facial malformation and has a significant developmental,
      physical, and psychological impact on those with the deformity and their
      families. In the United States, current estimates place the prevalence of cleft
      lip and palate or isolated cleft lip at approximately 1 in 600. There is
      significant phenotypic variation in the specific presentation of facial clefts.
      Understanding outcome data is important when making clinical decisions for
      patients with clefts. This article provides an update on current primary cleft
      lip and palate outcome data.

PMID- 20159478
TI  - Orbital surgery: state of the art.
AB  - Much has been written about the repair of orbital fractures, yet some debate
      still exists among surgeons with regard to indications for and timing of fracture
      repair and various surgical techniques. Controversies regarding the surgical
      maneuvers include the incision, surgical approach, and methods of wound closure.
      More detailed imaging modalities have allowed clinicians to understand the
      injuries more completely and plan for and execute more ideal reconstructions.
      Recent advances in orbital implant materials and the role of endoscopy in orbital
      fracture repair add to this debate about which techniques would be best for
      particular injuries. This article discusses these issues and provides the most
      current literature review regarding the management of various orbital fractures.

PMID- 20159479
TI  - Technology in microvascular surgery.
AB  - With the refinement of microvascular technique, free-tissue transfer has emerged
      as the standard of care in head and neck reconstruction. Success rates and
      reductions in operative time have reduced "flap take" from being the marker of
      reconstructive success to being an expectation. Interest has now shifted to
      improvement of technique, with surgeons placing increasing importance on donor
      site morbidity, quality of tissue harvested, and esthetic and functional
      outcomes. Much of the recent success can be attributed to technological advance
      through improvement in instrumentation and technique and enhancement of the
      understanding of flap physiology and anatomy. This article reviews some of the
      recent advances and how they have affected microvascular surgery from
      preoperative, operative, and postoperative standpoints.

PMID- 20159480
TI  - Temporary skeletal anchorage devices for orthodontics.
AB  - This article discusses the recent advances and basic concepts of skeletal
      anchorage devices of various types and reviews the current literature on their
      use. Temporary skeletal anchorage devices allow orthodontic movements that were
      previously thought to be difficult if not impossible. Much like the concepts
      introduced during the beginnings of orthognathic dentofacial teams, treatment
      that uses skeletal anchorage requires interdisciplinary collaboration and
      planning with regular interaction, continuing education, and a regular review of
      the latest relevant literature.

PMID- 20159481
TI  - Advances in head and neck imaging.
AB  - Imaging plays a key role in dental implantation, management of maxillofacial
      trauma, facial reconstruction, temporomandibular joint pathology, and evaluation
      and treatment of neoplasms and infections. In addition to traditional
      conventional radiography, recent advances in computer tomography, magnetic
      resonance imaging, and positron emission tomography-computed tomography fusion
      technology have made radiology an even more vital component of patient care in
      dental and craniomaxillofacial practice.

PMID- 20159482
TI  - Computer-assisted craniomaxillofacial surgery.
AB  - Computer-assisted surgery (CAS) describes all forms of surgery planning or
      execution that incorporate various forms of advanced imaging, software, analysis,
      and planning and, in some cases, rapid prototyping technology, robotics, and
      image-guidance systems. Innovation is progressing rapidly, and new forms of
      technology continue to be incorporated and evaluated for their value in improving
      daily operations. This article reviews imaging, enhanced three-dimensional
      diagnostics, tactile models, CAS concepts, reconstructive surgery, bone flap
      shaping, distraction osteogenesis, and orthognathic surgery in relation to
      craniomaxillofacial surgery.

PMID- 20159483
TI  - Computer planning and intraoperative navigation in cranio-maxillofacial surgery.
AB  - Preoperative computer design and stereolithographic modeling combined with
      intraoperative navigation provide a useful guide for and possibly more accurate
      reconstruction of a variety of complex cranio-maxillofacial deformities. Although
      probably not necessary for routine use, the author's early experience confirms
      that of other surgeons with more than a decade of experience: computer-assisted
      surgery is indicated for complex posttraumatic or postablative reconstruction of
      the orbits, cranium, maxilla, and mandible; total temporomandibular joint
      replacement; orthognathic surgery; and complex dental/craniofacial implantology.
      Further study is needed to provide outcomes data and cost-benefit analyses for
      each of these indications.

PMID- 20159484
TI  - Endonasal surgery of the ventral skull base--endoscopic transcranial surgery.
AB  - Skull base surgery is evolving from traditional transfacial and transcranial
      approaches to the endoscopic endonasal approach, a less intrusive corridor for
      accessing the ventral skull base. This technique eliminates facial scars,
      expedites recovery, and obviates brain retraction. The goals of surgical
      excision, whether palliative or curative, are identical: an approach that is less
      disruptive to normal tissues. By exploiting the sinonasal corridor, the entire
      ventral skull base may be accessed to successfully treat benign and malignant
      lesions. The expanding limits of endoscopic skull base surgery have been
      accompanied by commensurate innovations in reconstructive techniques that are
      reliable and have been shown to limit postoperative complications. This article
      describes the basis for this approach and provides the latest outcome data
      supporting the current state of the art for endoscopic skull base surgery.

PMID- 20159485
TI  - Endoscopic techniques in oral and maxillofacial surgery.
AB  - Oral and maxillofacial surgery is entering a new era. Surgeons can use the latest
      technological advances in equipment in an attempt to improve patient outcomes.
      Minimally invasive surgery with the use of the endoscope has improved in recent
      years because of technological advancements in optics and associated
      instrumentation. Trauma, orthognathic, sialoendoscopy, and temporomandibular
      joint surgery are commonly performed with the assistance of the endoscope. From
      an educational standpoint, surgical anatomy and various other principles can
      easily be taught to trainees with the assistance of the endoscope. The operating
      surgeon can visualize an area via the endoscope, and instruct regarding the
      surgical maneuvers on the monitor, without obstructions to view. This technique
      also allows others in and out of the room to view the image. Endoscopically
      assisted surgery is gaining popularity and is becoming a tool frequently used by
      surgeons to assist in and simplify some of the more difficult techniques that
      often require more extensive surgical exposure for visualization.

PMID- 20159486
TI  - Molecular diagnostics for head and neck pathology.
AB  - Molecular diagnostic techniques are quickly finding a role in the detection and
      diagnosis of tumors, and in predicting their behavior. They may also prove useful
      in developing new therapeutic approaches to head and neck cancer. The surgeon
      working in the craniomaxillofacial region should have an understanding of these
      technologies, their availability in various settings, and how they affect various
      aspects of treatment, particularly in the detection and treatment of
      malignancies. This article offers an overview of recent advances in molecular
      diagnostic techniques, with their implications for diagnosis and management of
      head and neck tumors.

PMID- 20159487
TI  - Adhesive use in oral and maxillofacial surgery.
AB  - Presently, tissue adhesives and sealants have limited use in oral and
      maxillofacial surgical procedures. Skin closure occurs regularly with
      cyanoacrylate adhesives. Sealing of dural tears in conjunction with dural closure
      has been shown to be very successful. With the development of more head and neck
      reconstructive procedures and cosmetic procedures, demand will increase for
      better surgical adhesives. Clinical trials are beginning for newly developed
      adhesives with the chemical characterizations, the safe reabsorptive profile, and
      the adhesive strength necessary to benefit oral and maxillofacial surgery
      patients in the near future. Adhesives for bone fixation, while in early
      development, also show a promising chemical profile and will be of significant
      benefit to oral and maxillofacial surgical patients.

PMID- 20159488
TI  - Neighborhood disadvantage and physical activity: baseline results from the
      HABITAT multilevel longitudinal study.
AB  - PURPOSE: To examine the association between neighborhood disadvantage and
      physical activity (PA). METHODS: We use data from the HABITAT multilevel
      longitudinal study of PA among middle-aged (40-65 years) men and women (N =
      11,037, 68.5% response rate) living in 200 neighborhoods in Brisbane, Australia.
      PA was measured using three questions from the Active Australia Survey (general
      walking, moderate, and vigorous activity), one indicator of total activity, and
      two questions about walking and cycling for transport. The PA measures were
      operationalized by using multiple categories based on time and estimated energy
      expenditure that were interpretable with reference to the latest PA
      recommendations. The association between neighborhood disadvantage and PA was
      examined with the use of multilevel multinomial logistic regression and Markov
      chain Monte Carlo simulation. The contribution of neighborhood disadvantage to
      between-neighborhood variation in PA was assessed using the 80% interval odds
      ratio. RESULTS: After adjustment for sex, age, living arrangement, education,
      occupation, and household income, reported participation in all measures and
      levels of PA varied significantly across Brisbane's neighborhoods, and
      neighborhood disadvantage accounted for some of this variation. Residents of
      advantaged neighborhoods reported significantly higher levels of total activity,
      general walking, moderate, and vigorous activity; however, they were less likely
      to walk for transport. There was no statistically significant association between
      neighborhood disadvantage and cycling for transport. In terms of total PA,
      residents of advantaged neighborhoods were more likely to exceed PA
      recommendations. CONCLUSIONS: Neighborhoods may exert a contextual effect on the
      likelihood of residents participating in PA. The greater propensity of residents
      in advantaged neighborhoods to do high levels of total PA may contribute to lower
      rates of cardiovascular disease and obesity in these areas.

PMID- 20159489
TI  - Lifestyle, anthropometric, and obesity-related physiologic determinants of
      insulin-like growth factor-1 in the Third National Health and Nutrition
      Examination Survey (1988-1994).
AB  - PURPOSE: Epidemiologic studies suggest that insulin-like growth factor-1 (IGF-1)
      is associated with obesity and, more recently, cancer. This study investigates
      multiple lifestyle, physiologic, and anthropometric determinants of circulating
      IGF-1 concentrations. METHODS: Nationally representative data were used from the
      cross-sectional Third National Health and Nutrition Examination (NHANES III, 1988
      1994) survey, which measured IGF-1 concentrations in blood, from a subsample of
      participants who were examined in the morning. After exclusion of persons with
      missing data, 6,058 men and women 20 years of age or older were included in the
      study. RESULTS: The mean IGF-1 concentrations were 260 ng/mL in the entire
      population and were higher among men as compared with women (278.8 vs. 241.3
      ng/mL; p<0.0001). IGF-1 decreased with increasing age (p<0.0001), body mass index
      (p<0.0001), and waist circumference (p<0.0001). Individuals with metabolic
      syndrome had lower IGF-1 concentrations after adjustment for covariates
      (p=0.0008). IGF-1 was inversely associated with increasing number of metabolic
      syndrome abnormalities (p=0.0008). All associations were stronger among women
      compared with men except across concentrations of glucose. IGF-1 concentrations
      did not vary by any other lifestyle or physiologic factors. CONCLUSIONS: Age,
      adiposity, hyperglycemia, and metabolic syndrome influenced circulating IGF-1
      concentrations. Diet and physical activity had no impact on IGF-1 in this
      nationally representative population.

PMID- 20159490
TI  - Correlates of weight patterns during middle age characterized by functional
      principal components analysis.
AB  - PURPOSE: Describing weight trajectories using functional methods may further our
      understanding of how weight impacts health. We characterize weight patterns and
      describe correlates of these patterns. METHODS: Using a subset of the Framingham
      Heart Study original cohort limited-access data set (n=1,429), we conducted a
      functional principal components analysis (PCA) of body mass index from 40 to 55
      years of age. Scores from the principal component functions defined weight
      patterns. Gender-specific logistic regression models provided estimates of
      association with sociodemographic and lifestyle factors. RESULTS: Overall weight
      status, weight changes, and cycling emerged as weight patterns during middle age.
      Overweight/obesity at 25 years was the most consistent correlate of weight
      patterns (adjusted odds ratios [AORs] for men and women were 14.2 and 3.7 for
      overall overweight, 99.5 and 28.3 for overall obese, and 1.4 and 3.9 for
      cycling). Weight status at 25 years was not associated with weight gain in either
      gender or weight loss in men; for women the AOR was 2.7 for weight loss.
      CONCLUSIONS: Functional PCA described weight patterns during middle age. The
      strong associations between weight status at 25 years and overall weight status
      and cycling during middle age underscore the importance of addressing weight
      earlier in life.

PMID- 20159491
TI  - Body composition among HIV-seropositive and HIV-seronegative adult patients with
      pulmonary tuberculosis in Uganda.
AB  - PURPOSE: We determined whether human immunodeficiency virus (HIV) infection
      affects body cell mass and fat mass wasting among adults with pulmonary
      tuberculosis (PTB). METHODS: We screened 967 Ugandan adults for PTB and HIV
      infection in a cross-sectional study. We compared anthropometric and bioelectric
      impedance analysis (BIA) body composition parameters among HIV-seropositive and
      HIV-seronegative men and women with or without PTB by using a non-parametric
      test. RESULTS: We found that poor nutritional status associated with TB differed
      among men and women. Anthropometric and BIA body composition did not differ
      between HIV-seropositive and HIV-seronegative patients regardless of gender.
      Average weight group difference in men consisted of body cell mass and fat mass
      in equal proportions of 43%. In women, average weight group difference consisted
      predominantly of fat mass of 73% and body cell mass of 13%. Compared to
      individuals without TB, patients with TB had lower body mass index, weight, body
      cell mass, and fat mass regardless of gender and HIV status. CONCLUSIONS: Gender,
      but not HIV status, was associated with body composition changes in TB. TB
      appears to be the dominant factor driving the wasting process among co-infected
      patients.

PMID- 20159493
TI  - Periconceptional multivitamin use and infant birth weight disparities.
AB  - PURPOSE: In the United States, African American women deliver preterm and low
      birth weight infants two to three times more frequently than their white
      counterparts. Our objective was to determine whether maternal periconceptional
      multivitamin (MVI) use is associated with this disparity. METHODS: As a secondary
      analysis of previously collected data from mothers of non-malformed infants from
      the Slone Epidemiology Center Birth Defects Study, we conducted a retrospective
      cohort study of 2331 non-Hispanic white and 133 non-Hispanic black mother/infant
      pairs from 1998 through 2007. To estimate the effect of MVI use on birth
      outcomes, linear regression models were used. RESULTS: In white subjects, MVI use
      was not associated with birth weight, gestational age, or weight-for-gestational
      age. However, in black subjects, MVI use was associated with a 536-gram increased
      birth weight (p=0.001). Black MVI users also had longer gestations (although not
      statistically significant). When birth weights were adjusted for gestational age
      using z scores, MVI use was associated with increased fetal growth in black
      infants (+0.86 z score units, 95% confidence interval: 0.35-1.36). CONCLUSIONS:
      The present findings suggest MVI use may improve fetal growth and possibly
      gestational age in the offspring of African American women.

PMID- 20159492
TI  - Predictors of mortality in elderly subjects with obstructive airway disease: the
      PILE score.
AB  - PURPOSE: To identify significant covariates in addition to spirometry that
      predict mortality in elderly subjects with obstructive airway disease (OAD).
      METHODS: Two hundred sixty-eight (268) participants with OAD from the Health,
      Aging and Body Composition study, a community-based observational cohort of well
      functioning elderly aged 70-79 years, were followed on average for 6.1 years.
      Covariates related to pulmonary and physical function, comorbidity, demographics,
      and three inflammatory markers (interleukin-6, tumor necrosis factor-alpha, C
      reactive protein) were evaluated for their association with all-cause mortality
      (31%) by means of Kaplan Meier analysis and Cox proportional hazards modeling.
      RESULTS: Percent predicted forced expiratory volume in one second (PPFEV1; hazard
      ratio [HR] = 2.03, p < 0.0001), knee extensor strength (HR = 1.36, p = 0.0002),
      interleukin-6 (HR = 1.37, p = 0.0002) and 400 m corridor walk time (HR = 1.24, p
      = 0.008) significantly predicted mortality. A multidimensional index, the PILE
      score, was constructed from PPFEV(1), interleukin-6, and knee extensor strength.
      Each one-point increase in PILE score (range: 1-10) was associated with a 30%
      increase in mortality (95% confidence interval: 0.16-0.47) after adjusting for
      age, race, gender, smoking, and comorbidity, resulting in a 10.4-fold higher risk
      of death between the highest and lowest risk category. CONCLUSIONS: Subjects with
      OAD have a wide gradient of risk for mortality that can potentially be
      incorporated in clinical decision making.

PMID- 20159494
TI  - Support for adolescents who experience parental military deployment.